PMID- 26256213 TI - Rif1 Is Required for Resolution of Ultrafine DNA Bridges in Anaphase to Ensure Genomic Stability. AB - Sister-chromatid disjunction in anaphase requires the resolution of DNA catenanes by topoisomerase II together with Plk1-interacting checkpoint helicase (PICH) and Bloom's helicase (BLM). We here identify Rif1 as a factor involved in the resolution of DNA catenanes that are visible as ultrafine DNA bridges (UFBs) in anaphase to which PICH and BLM localize. Rif1, which during interphase functions downstream of 53BP1 in DNA repair, is recruited to UFBs in a PICH-dependent fashion, but independently of 53BP1 or BLM. Similar to PICH and BLM, Rif1 promotes the resolution of UFBs: its depletion increases the frequency of nucleoplasmic bridges and RPA70-positive UFBs in late anaphase. Moreover, in the absence of Rif1, PICH, or BLM, more nuclear bodies with damaged DNA arise in ensuing G1 cells, when chromosome decatenation is impaired. Our data reveal a thus far unrecognized function for Rif1 in the resolution of UFBs during anaphase to protect genomic integrity. PMID- 26256212 TI - Axud1 Integrates Wnt Signaling and Transcriptional Inputs to Drive Neural Crest Formation. AB - Neural crest cells are induced at the neural plate border by the combined action of transcription factors and signaling molecules. Here, we show that Axud1, a downstream effector of Wnt signaling, represents a critical missing link that integrates signaling and transcriptional cues to mediate neural crest formation. Axud1 is a transcription factor expressed in neural crest progenitors in a Wnt1/beta-catenin-dependent manner. Axud1 loss leads to downregulation of multiple genes involved in neural crest specification, similar to the effects of Wnt1 knockdown. Importantly, Axud1 is sufficient to rescue neural crest formation after disruption of Wnt signaling. Furthermore, it physically interacts with neural plate border genes Pax7 and Msx1 in vivo to directly activate transcription of stem cell factor FoxD3, initiating the neural crest program. Thus, Axud1 integrates Wnt signaling with transcriptional inputs to endow the neural crest with its unique molecular signature. PMID- 26256214 TI - ASPMN: A Relationship that Continues to Grow Sweeter Each Year. PMID- 26256215 TI - Evaluation of Evidence-based Nursing Pain Management Practice. AB - It is important to ensure that cancer pain management is based on the best evidence. Nursing evidence-based pain management can be examined through an evaluation of pain documentation. The aim of this study was to modify and test an evaluation tool for nursing cancer pain documentation, and describe the frequency and quality of nursing pain documentation in one oncology unit via the electronic medical system. A descriptive cross-sectional design was used for this study at an oncology unit of an academic medical center in the Pacific Northwest. Medical records were examined for 37 adults hospitalized during April and May 2013. Nursing pain documentations (N = 230) were reviewed using an evaluation tool modified from the Cancer Pain Practice Index to consist of 13 evidence-based pain management indicators, including pain assessment, care plan, pharmacologic and nonpharmacologic interventions, monitoring and treatment of analgesic side effects, communication with physicians, and patient education. Individual nursing documentation was assigned a score ranging from 0 (worst possible) to 13 (best possible), to reflect the delivery of evidence-based pain management. The participating nurses documented 90% of the recommended evidence-based pain management indicators. Documentation was suboptimal for pain reassessment, pharmacologic interventions, and bowel regimen. The study results provide implications for enhancing electronic medical record design and highlight a need for future research to understand the reasons for suboptimal nursing documentation of cancer pain management. For the future use of the data evaluation tool, we recommend additional modifications according to study settings. PMID- 26256216 TI - Nonpharmacologic Pain Management Interventions in German Nursing Homes: A Cluster Randomized Trial. AB - The reported prevalence of pain among nursing home residents (NHRs) is high. Insufficient use of analgesics, the conventional pain management strategy, is often reported. Whether and to what extent nonpharmacologic therapies (NPTs) are used to manage the pain of NHRs in Germany is largely unknown. The aim of this cluster-randomized trial was to assess the NPTs provided and to enhance the application and prescription of NPTs in NHRs on an individual level. There were six nursing homes in the intervention group and six in the control group. There were 239 NHRs, aged >=65 years, with an average Mini-Mental State Examination score of at least 18 at baseline. Pain management interventions (cluster level) included an online course for physicians and 1-day seminar for nurses. Data on NPT applied by nurses and therapeutic NPT prescribed by physicians were obtained from residents' nursing documentation. Face-to-face interviews with NHRs assessed the NPT received. At baseline, 82.6% of NHR (mean age 83 years) were affected by pain, but less than 1 in 10 received NPT. The intervention did not result in a significant increase in the NPT applied by nurses, but did significantly increase the therapeutic NPT prescribed by physicians. Residents were active in using NPT to self-manage their pain. Given the prevalence of pain in NHRs, there is a clear need to improve pain management in this population. Extended use of NPT offers a promising approach. We recommend that nurses provide residents with education on pain-management techniques to support them in taking a proactive role in managing their pain. PMID- 26256217 TI - Psychometric Evaluation of the Revised Iowa Pain Thermometer (IPT-R) in a Sample of Diverse Cognitively Intact and Impaired Older Adults: A Pilot Study. AB - Self-report pain assessment tools are commonly used in clinical settings to determine patients' pain intensity. The Iowa Pain Thermometer (IPT) is a tool that was developed for research, but also can be used in clinical settings. However, its utility in clinical settings is challenging because it uses a 13 point scale (0-12 scale) that does not align with common electronic pain scoring metrics. Therefore, this study evaluated the psychometric properties of an 11 point (0-10 scale) adaptation of the Iowa Pain Thermometer (IPT-R) to evaluate the psychometric properties of the IPT-R and to determine patient preference for a self-report pain assessment tool. A descriptive, correlational design was employed. The IPT-R was compared with the original IPT and a numeric rating scale (NRS). This study was conducted in the southeastern United States with 75 adults ranging in age from 65-95 years with varying levels of cognition. Participants were primarily representative of black and white backgrounds. Participants were asked to rate current pain, worst pain during the past week, and reassessment of current pain after 10-minute intervals using three scales (IPT-R, IPT, and NRS) presented in random order. Participants were asked to identify the tool preferred (the easiest to use and that best represented their pain intensity). Spearman rank correlations were performed to determine convergent validity and test-retest reliability. Based on the results of this preliminary study, the IPT-R has good validity and reliability. The participants in this sample preferred the IPT-R over the original IPT (0-12 scale) and the traditional NRS (0-10 scale). Clinicians may consider using this tool with diverse older patients to assess pain intensity. PMID- 26256218 TI - Prevalence and Factors Affecting Dysmenorrhea in Female University Students: Effect on General Comfort Level. AB - The purpose of this study was to investigate the prevalence and the affecting factors of dysmenorrhea and its effects on overall comfort among female university students. This was a cross-sectional study. The research was carried out between October and November 2013 at a university in Ankara. This study was conducted with 200 female students. The data were analyzed using frequencies, means, SD, chi(2) tests, independent t tests and analysis of variance. Data were collected using an interview questionnaire, the visual analog scale (VAS) and the General Comfort Questionnaire. The mean age of students in this study group was 20.85 +/- 2.15 years. The prevalence of dysmenorrhea in the students was 84%. The mean severity of pain was 5.78 +/- 2.45 on the VAS. The present study found that 45.8% of female students experienced moderate menstrual pain and the most common co-occurring symptoms were irritability (34.6%) and fatigue (21.5%). One-fourth of the students with dysmenorrhea consulted the advice of a physician and the most commonly used methods for pain were analgesics (69%), heat application (56.5%), and rest (71.4%). Family history of dysmenorrhea, education about menstruation, and frequency of menstrual cycle were identified as important factors in the development of dysmenorrhea (p < .05). The mean general comfort score for students with dysmenorrhea (2.57 +/- 0.25) was lower than that of students without the condition (2.65 +/- 0.23). Also, use of the methods for management of dysmenorrhea was found to increase students' general comfort levels. Therefore, it is important for nurses to educate and advise adolescents and young women about dysmenorrhea. PMID- 26256219 TI - Satisfaction with and Perception of Pain Management among Palliative Patients with Breakthrough Pain: A Qualitative Study. AB - Breakthrough pain is a significant contributor to much suffering by patients. The experience of intense pain may interfere with, and affect, daily life functioning and has major consequences on patients' well-being if it is not well managed. The area of breakthrough pain has not been fully understood. This study thus aimed to explore the experiences of breakthrough pain among palliative patients. A qualitative study based on a series of open-ended interviews among 21 palliative patients suffering from pain at an urban tertiary hospital in Malaysia was conducted. Five themes were generated: (i) pain viewed as an unbearable experience causing misery in the lives of patients, (ii) deterioration of body function and no hope of recovery, (iii) receiving of inadequate pain management for pain, (iv) insensitivity of healthcare providers toward patients' pain experience, and (v) pain coping experiences of patients. The findings revealed that nonpharmacologic approaches such as psychosocial support should be introduced to the patients. Proper guidance and information should be given to healthcare providers to improve the quality of patient care. Healthcare providers should adopt a sensitive approach in caring for patients' needs. The aim is to meet the needs of the patients who want to be pain free or to attain adequate relief of their pain for breakthrough pain. PMID- 26256220 TI - A Proposed Model of the Effective Management of Children's Pain. AB - The aim of this study was to understand the various factors that contribute to the delivery of effective pain management. The current picture of pain management is complex and contradictory, with children in the hospital still experiencing unnecessary pain, nurses reporting better pain care than is evidenced, and parents who are reluctant to report their child's pain. There is a real need to focus on areas of excellence where pain management innovations have been successfully implemented. Five hospitals were visited in three countries: the United Kingdom, Sweden, and Australia, spending a week in each country. In all, 28 health care professionals were interviewed exploring innovations in pain management; the effect of improvements on children, parents, and nurses; and what helped and hindered the delivery of effective pain management. Better pain management provides nurses with confidence, which in turn gives children and parents confidence in their care and reduces anxiety for nurses. Resources, on the other hand, were a common issue in relation to obstacles to innovation. A recurring theme in all areas visited was the issue of culture and how it affected both negatively and positively on the management of children's pain. Strong leadership was integral to moving practice forward and to introducing the innovations that led to effective pain management. The key findings identified that underpin the effective management of children's pain are effective leadership, resources, and confidence; the consequences are less stress for children and nurses, more trusting relationships, and greater job satisfaction. A model of effective pain management is proposed. PMID- 26256221 TI - Examining Validity and Reliability of the Emotional Reactions Checklist with Hospitalized Children. AB - Fear, anxiety, and emotional upset are common experiences for hospitalized children. To identify and treat children's emotional reactions, health care professionals must be able to differentiate emotional reactions from pain and other symptoms. Clinical assessment of emotions requires the use of valid and reliable instruments in acute care settings. This study examined internal consistency, construct, and concurrent validity of the Emotional Reactions Checklist (ERC). A descriptive correlational design guided the psychometric approach. Children answered a sociodemographic questionnaire and responded to self-generated scenarios of pleasant and unpleasant events using two self-report scales of emotions. The convenience sample comprised 59 children admitted to an inpatient unit in a large children's hospital or to a community hospital emergency department. Construct validity was supported by significantly different ERC mean responses to recalled pleasant prehospitalization experiences and unpleasant hospitalization experiences (p < .001) for both ERC item responses and total scale scores. Children's explanations for seemingly inconsistent item responses further supported their ability to use the ERC to convey their emotions. Concurrent validity was supported by moderate (r = 0.32) to strong (r = 0.70) correlations between the Facial Affective Scale and ERC items and scale scores. Internal consistency was better supported for the recalled unpleasant experience (alpha = 0.77) than for the pleasant experience (alpha = 0.60). Results supported construct and concurrent validity and beginning internal consistency reliability for the ERC in an acute care setting. Further research is required to establish feasibility of repeated use with ill children. PMID- 26256222 TI - The Pain Management Life History Calendar: A Pilot Study. AB - Pain management trajectory data that includes previous pain treatments, timing, changes, and outcomes provide crucial data for patients with chronic pain and their practitioners to use when discussing ways to optimize pain management regimens. The aim of this study was to test the use of the life history calendar method to identify pain treatments, treatment regimens, timing, and outcomes of the pain management trajectory of individuals with chronic pain, and to examine feasibility. A pilot, descriptive, methodological design was used. Settings included community-based sites such as congregate housing. Nineteen community dwelling older adults with osteoarthritis (OA) pain of at least 1 year's duration participated. Participants were interviewed and asked to chronicle from the beginning of the OA pain to the present all of their pain treatments and treatment effects (pain outcomes and adverse events). Raters independently content analyzed the transcribed interviews to identify pain treatments, treatment groupings (regimens), and treatment effects on pain. Feasibility of patients reporting their pain management trajectories was content analyzed by identifying participant difficulty identifying pain treatments, treatment effects, treatment sequence; and difficulty discriminating between treatments, and between OA pain and other pain sources. Individual pain management trajectories were constructed that depicted chronological order of pain treatment regimens and treatment effects. Participants identified pain treatments, discriminate between treatments and between OA and other conditions, and identified treatment effects. Treatment sequence was identified, but more precise timing was generally not reported. Pain management trajectories could provide a helpful way for practitioners to discuss safe, efficacious pain management options with patients. PMID- 26256223 TI - Pain Assessment and Management in Nursing Education Using Computer-based Simulations. AB - It is very important for nurses to have a clear understanding of the patient's pain experience and of management strategies. However, a review of the nursing literature shows that one of the main barriers to proper pain management practice is lack of knowledge. Nursing schools are in a unique position to address the gap in pain management knowledge by facilitating the acquisition and use of knowledge by the next generation of nurses. The purpose of this article is to discuss the role of computer-based simulations as a reliable educational technology strategy that can enhance the learning experience of nursing students acquiring pain management knowledge and practice. Computer-based simulations provide a significant number of learning affordances that can help change nursing students' attitudes and behaviors toward and practice of pain assessment and management. PMID- 26256224 TI - Where Are We: A Systematic Evaluation of the Psychometric Properties of Pain Assessment Scales for Use in Chinese Children. AB - Systematic pain assessment using reliable and valid pain scales is the foundation for optimal pain management in children. To evaluate the available scales for pain assessment in Chinese children, we systematically evaluated the psychometric properties of pain measurements used in Chinese children. We searched Chinese- and English-language databases from their inception to September 2013. Studies were eligible for inclusion if the psychometric properties of pain measures were examined in Chinese children (aged 0-18 years). Two bilingual reviewers independently evaluated the psychometric properties of the identified pain scales by a revised 11-item coding system. In all, 6 studies involving 775 participants were included in this review with six pain scales examined, including the Face, Legs, Activity, Cry, and Consolability (FLACC) Scale, COMFORT-Behavior Scale, Asian Version of Oucher Scale, Pain Observation Scale for Young Children (POCIS), Neonatal Facial Coding System (NFCS) and Pain Assessment Scale for Preterm Infants (PASPI). The FLACC, COMFORT-Behavior Scale, and PASPI had very good psychometric qualities when administered in Chinese children; the Asian Version of Oucher Scale and POCIS showed acceptable to good psychometric qualities; and the NFCS had unacceptable psychometric qualities. Further psychometric testing of these observational measures and self-report pain scales in particular are needed among Chinese children of various age groups and in different pain situations. PMID- 26256225 TI - Results of Arthroscopic Bankart Lesion Repair in Patients with Post-Traumatic Anterior Instability of the Shoulder and a Non-Engaging Hill-Sachs Lesion with a Suture Anchor after a Minimum of 6-Year Follow-Up. AB - BACKGROUND: Shoulder instability is an important clinical problem. Arthroscopic surgery is an established treatment modality in shoulder instability, but it continues to be associated with a high rate of recurrences and complications. The purpose of the study was to analyze late outcomes of arthroscopic repair of Bankart lesions in patients with post-traumatic anterior shoulder instability and non-engaging Hill-Sachs lesion, with special focus on the incidence and causes of recurrences and complications. MATERIAL AND METHODS: We investigated 92 patients (92 shoulders) who underwent surgery on account of post-traumatic anterior shoulder instability. The duration of follow-up ranged from 6 to 12.5 years (mean: 8.2 years). All patients were operated on in the lateral decubitus position using FASTak 2.8-mm suture anchors (FASTak, Arthrex, Naples, Florida). Treatment outcomes were evaluated using the Rowe and University of California at Los Angeles rating system (UCLA). RESULTS: According to Rowe scores, there were 71 (81.5%) excellent, 12 (12.6%) good, 5 (5.3%) satisfactory, and 2 (2.1%) poor results. Rowe scores improved in a statistically significant manner (p=0.00) post surgery, to a mean of 90 (range: 25-100). Treatment outcomes measured as UCLA scores improved in a statistically significant manner (p=0.00), reaching post operative levels of 12-35 (mean: 33.5). There were 9 recurrences, 1 case of axillary nerve praxia, and 1 case of anchor loosening. CONCLUSIONS: With rigorous criteria for qualifying patients for surgery, arthroscopic treatment of post traumatic anterior shoulder instability produces good outcomes and low recurrence and complication rates irrespective of the number of previous dislocations, age, or sex. PMID- 26256226 TI - Effect of parity on healthy promotion lifestyle behavior in women. AB - BACKGROUND: Health-promoting lifestyle behaviors are not only for the prevention of a disease or discomfort, but are also behaviors that aim to improve the individual's general health and well-being. Nurses have an important position in the development of healthy lifestyle behaviors in women. OBJECTIVE: The aim of this study was to assess the effect of parity on health-promoting lifestyle behaviors in women. METHOD/DESIGN: This descriptive and cross-sectional survey was performed in Adana, Turkey. This study was conducted with 352 women. The questionnaire consisted of two parts; the first part consisted of questions that assessed the socio-demographic and obstetric characteristics, and the second part employed the "Health Promotion Lifestyle Profile Scale" (HPLP). Data analysis included percentage, arithmetic average, and ANOVA tests. RESULTS: The results revealed that 24.1% of the women had no parity, 13.6% had one parity, 30.7% had two parities, 14.6% had three parities, and 17% had four and above parities. The mean total HPLP was 126.66+/-18.12 (interpersonal support subscale, 24.46+/-4.02; nutrition subscale, 21.59+/-3.92; self-actualization subscale, 24.42+/-4.30; stress management subscale, 18.73+/-3.81; health responsibility subscale, 21.75+/ 4.31; and exercise subscale, 15.71+/-4.22). CONCLUSIONS: The health behavior of women was moderate. A statistically significant correlation was found between the number of parities and the Health Responsibility, Nutrition, Interpersonal Support, which is the subscale of the HPLP Scale. PMID- 26256228 TI - Arterial blood gas anomaly in canine hepatobiliary disease. AB - Arterial blood gas analysis is an important diagnostic and monitoring tool for respiratory abnormalities. In human medicine, lung complications often occur as a result of liver disease. Although pulmonary complications of liver disease have not been reported in dogs, we have frequently encountered hypoxemia in dogs with liver disorders, especially extrahepatic biliary obstruction. In addition, respiratory disorders account for 20% of perioperative fatalities in dogs. Therefore, in this study, we evaluated the respiratory status in dogs with hepatobiliary disease by arterial blood gas analysis. PaO2 and PaCO2 were measured. Alveolar-arterial oxygen difference (AaDO2), the indicator of gas exchange efficiency, was calculated. Compared to healthy dogs (control group), hepatobiliary disease dogs had significantly lower PaO2 and higher AaDO2. Hypoxemia (PaO2 of <=80 mmHg) was observed in 28/71 dogs with hepatobiliary disease. AaDO2 was higher (>=30 mmHg) than the control group range (11.6 to 26.4 mmHg) in 32/71 hepatobiliary disease dogs. By classifying type of hepatobiliary disease, dogs with extrahepatic biliary obstruction and chronic hepatitis showed significantly lower PaO2 and higher AaDO2 than in a control group. Dogs with chronic hepatitis also had significantly lower PaCO2. The present study shows that dogs with hepatobiliary disease have respiratory abnormalities more than healthy dogs. Preanesthetic or routine arterial blood gas analysis is likely beneficial to detect the respiratory abnormalities in dogs with hepatobiliary disease, especially extrahepatic biliary obstruction and chronic hepatitis. PMID- 26256227 TI - Physical Principles of Nanoparticle Cellular Endocytosis. AB - This review article focuses on the physiochemical mechanisms underlying nanoparticle uptake into cells. When nanoparticles are in close vicinity to a cell, the interactions between the nanoparticles and the cell membrane generate forces from different origins. This leads to the membrane wrapping of the nanoparticles followed by cellular uptake. This article discusses how the kinetics, energetics, and forces are related to these interactions and dependent on the size, shape, and stiffness of nanoparticles, the biomechanical properties of the cell membrane, as well as the local environment of the cells. The discussed fundamental principles of the physiochemical causes for nanoparticle cell interaction may guide new studies of nanoparticle endocytosis and lead to better strategies to design nanoparticle-based approaches for biomedical applications. PMID- 26256229 TI - Computed tomographic images of discospondylitis in a calf. AB - A 2-month-old male Japanese Black calf was presented with a 30-day history of progressive ataxia. Antemortem examination using computed tomography (CT) revealed narrowing of the disc spaces due to destruction of intervertebral structures between the first and second thoracic vertebrae and between the second and third thoracic vertebrae. Osteolysis was evident as irregular hypoattenuating lesions within the opposing end plates of the first, second and third thoracic vertebrae. Pseudomonas aeruginosa was detected as the causative bacteria, and discospondylitis was diagnosed. To the best of our knowledge, this is the first bovine case report describing the application of CT for the diagnosis of discospondylitis. PMID- 26256230 TI - Molecular cloning of feline resistin and the expression of resistin, leptin and adiponectin in the adipose tissue of normal and obese cats. AB - Resistin, one of the adipokines that has a cycteine-rich C-terminus, is considered to relate to the development of insulin resistance in rats. However, in cats, there is little knowledge regarding resistin. In this study, we cloned the feline resistin cDNA from adipose tissue by RT-PCR. The feline resistin clone contained an entire open reading frame encoding 107 amino acids that had 72.8%, 75.4%, 50.9% and 51.8% homology with bovine, human, mouse and rat homologues, respectively. In both subcutaneous and visceral adipose tissues, the transcription levels of feline resistin mRNA were significantly higher in obese cats than normal cats, and those of feline adiponectin mRNA were significantly lower in obese cats than normal cats. However, there was no difference in the expression of feline leptin between normal and obese cats. On the other hand, in both normal and obese cats, there were no significant differences in resistin, leptin and adiponectin mRNA levels between subcutaneous and visceral adipose tissues. In cats, the altered expression of resistin and adiponectin mRNA with obesity may contribute to the pathogenesis of insulin resistance and subsequent diabetes mellitus. In addition to feline adiponectin, the feline resistin cDNA clone obtained in this study will be useful for further investigation of the pathogenesis of obesity in cats. PMID- 26256231 TI - Change in intrarenal Ghrelin expression in immune complex-mediated glomerular disease in dogs. AB - Ghrelin is a peptide hormone that is mainly produced by the stomach. The kidney is a major source of local ghrelin, and maintaining body fluid balance is considered a critical role of renal ghrelin. However, there are no reports on renal ghrelin in small animal medicine. The present study investigated the intrarenal localization of and change in ghrelin expression in dogs with immune complex-mediated glomerulonephritis (ICGN). Ghrelin immunoreactivity (IR) was observed in the distal tubules of normal kidneys. Ghrelin IR was weak in ICGN kidneys, and the quantitative ghrelin IR score was significantly lower in ICGN kidneys than in normal kidneys. In cases of ICGN, plasma creatinine concentrations showed a positive correlation with the ghrelin IR score. PMID- 26256232 TI - Infection of Melissococcus plutonius clonal complex 12 strain in European honeybee larvae is essentially confined to the digestive tract. AB - Melissococcus plutonius is an important pathogen that causes European foulbrood (EFB) in honeybee larvae. Recently, we discovered a group of M. plutonius strains that are phenotypically and genetically distinct from other strains. These strains belong to clonal complex (CC) 12, as determined by multilocus sequence typing analysis, and show atypical cultural and biochemical characteristics in vitro compared with strains of other CCs tested. Although EFB is considered to be a purely intestinal infection according to early studies, it is unknown whether the recently found CC12 strains cause EFB by the same pathomechanism. In this study, to obtain a better understanding of EFB, we infected European honeybee (Apis mellifera) larvae per os with a well-characterized CC12 strain, DAT561, and analyzed the larvae histopathologically. Ingested DAT561 was mainly localized in the midgut lumen surrounded by the peritrophic matrix (PM) in the larvae. In badly affected larvae, the PM and midgut epithelial cells degenerated, and some bacterial cells were detected outside of the midgut. However, they did not proliferate in the deep tissues actively. By immunohistochemical analysis, the PM was stained with anti-M. plutonius serum in most of the DAT561-infected larvae. In some larvae, luminal surfaces of the PM were more strongly stained than the inside. These results suggest that infection of CC12 strain in honeybee larvae is essentially confined to the intestine. Moreover, our results imply the presence of M. plutonius-derived substances diffusing into the larval tissues in the course of infection. PMID- 26256233 TI - SCA 8 mimicking MSA-C. PMID- 26256234 TI - Quantum Mechanics and Molecular Mechanics Study of the Catalytic Mechanism of Human AMSH-LP Domain Deubiquitinating Enzymes. AB - Deubiquitinating enzymes (DUBs) catalyze the cleavage of the isopeptide bond in polyubiquitin chains to control and regulate the deubiquitination process in all known eukaryotic cells. The human AMSH-LP DUB domain specifically cleaves the isopeptide bonds in the Lys63-linked polyubiquitin chains. In this article, the catalytic mechanism of AMSH-LP has been studied using a combined quantum mechanics and molecular mechanics method. Two possible hydrolysis processes (Path 1 and Path 2) have been considered. Our calculation results reveal that the activation of Zn(2+)-coordinated water molecule is the essential step for the hydrolysis of isopeptide bond. In Path 1, the generated hydroxyl first attacks the carbonyl group of Gly76, and then the amino group of Lys63 is protonated, which is calculated to be the rate limiting step with an energy barrier of 13.1 kcal/mol. The energy barrier of the rate limiting step and the structures of intermediate and product are in agreement with the experimental results. In Path 2, the protonation of amino group of Lys63 is prior to the nucleophilic attack of activated hydroxyl. The two proton transfer processes in Path 2 correspond to comparable overall barriers (33.4 and 36.1 kcal/mol), which are very high for an enzymatic reaction. Thus, Path 2 can be ruled out. During the reaction, Glu292 acts as a proton transfer mediator, and Ser357 mainly plays a role in stabilizing the negative charge of Gly76. Besides acting as a Lewis acid, Zn(2+) also influences the reaction by coordinating to the reaction substrates (W1 and Gly76). PMID- 26256235 TI - Enantioselective cascade double Michael addition of 3-nitro-2H-chromenes and acyclic enones: efficient synthesis of functionalized tricyclic chroman derivatives. AB - An efficient protocol for the asymmetric construction of enantiomerically enriched tetrahydro-6H-benzo[c]chromenes and their derivatives has been developed. The corresponding products were obtained by the cascade double Michael addition of 3-nitro-2H-chromenes and their derivatives with alpha,beta unsaturated ketones catalyzed by a combination of a quinine-derived primary amine and benzoic acid. Through this methodology, the desired products could be obtained in moderate to good yields (up to 90%), with excellent diastereoselectivities (up to >25 : 1 dr) and moderate to excellent enantioselectivities (up to 95% ee). PMID- 26256236 TI - Addictive-Like Eating, Body Mass Index, and Psychological Correlates in a Community Sample of Preadolescents. AB - INTRODUCTION: The two main objectives were to identify addictive-like eating in youth and determine the relationship between addictive-like eating, hedonic hunger, and psychological variables. METHOD: A cross-sectional design was used. Each subject's objective heights and weights were measured. Subjects completed questionnaires about anxiety, depression, appetitive responsiveness, addictive like eating, other forms of disordered eating, and exercise patterns. RESULTS: Sixty-five children, ages 9 to 14 years, participated in the study. The mean body mass index percentile for age and gender was 69%. Thirty-eight percent of the children were either overweight or obese. Sixteen percent reported three or more addictive-like eating behaviors, and 4% met the criteria for "food addiction." Addictive-like eating was significantly correlated with appetitive responsiveness but not body mass index, anxiety, depression, or other measures of disordered eating. DISCUSSION: Addictive-like eating occurs in children as young as 9 years and appears to be a different type of disordered eating. The hedonic value and proximity of food is a contributor to addictive-like eating behaviors. PMID- 26256239 TI - Bottom-up assembly of metallic germanium. AB - Extending chip performance beyond current limits of miniaturisation requires new materials and functionalities that integrate well with the silicon platform. Germanium fits these requirements and has been proposed as a high-mobility channel material, a light emitting medium in silicon-integrated lasers, and a plasmonic conductor for bio-sensing. Common to these diverse applications is the need for homogeneous, high electron densities in three-dimensions (3D). Here we use a bottom-up approach to demonstrate the 3D assembly of atomically sharp doping profiles in germanium by a repeated stacking of two-dimensional (2D) high density phosphorus layers. This produces high-density (10(19) to 10(20) cm(-3)) low-resistivity (10(-4)Omega . cm) metallic germanium of precisely defined thickness, beyond the capabilities of diffusion-based doping technologies. We demonstrate that free electrons from distinct 2D dopant layers coalesce into a homogeneous 3D conductor using anisotropic quantum interference measurements, atom probe tomography, and density functional theory. PMID- 26256240 TI - Modelling the mechanics and hydrodynamics of swimming E. coli. AB - The swimming properties of an E. coli-type model bacterium are investigated by mesoscale hydrodynamic simulations, combining molecular dynamics simulations of the bacterium with the multiparticle particle collision dynamics method for the embedding fluid. The bacterium is composed of a spherocylindrical body with attached helical flagella, built up from discrete particles for an efficient coupling with the fluid. We measure the hydrodynamic friction coefficients of the bacterium and find quantitative agreement with experimental results of swimming E. coli. The flow field of the bacterium shows a force-dipole-like pattern in the swimming plane and two vortices perpendicular to its swimming direction arising from counterrotation of the cell body and the flagella. By comparison with the flow field of a force dipole and rotlet dipole, we extract the force-dipole and rotlet-dipole strengths for the bacterium and find that counterrotation of the cell body and the flagella is essential for describing the near-field hydrodynamics of the bacterium. PMID- 26256241 TI - Establishment of a two-dimensional chiral HPLC system for the simultaneous detection of lactate and 3-hydroxybutyrate enantiomers in human clinical samples. AB - A two-dimensional chiral high-performance liquid chromatography system was established for simultaneous detection of lactate (LA) and 3-hydroxybutyrate (3HB) enantiomers in human clinical samples. d-LA is increased upon kidney damage but 3HB protected against kidney injury. Therefore, determining the concentrations of D,L-LA and D,L-3HB simultaneously would be useful for evaluating pathological conditions. LA and 3HB were pre-column-derivatized with the fluorescent reagent 4-(N-chloroformylmethyl-N-methylamino)-7-nitro-2,1,3 benzoxadiazole (NBD-COCl) at 60 degrees C for 15 min and separated in the first dimension with a capillary monolithic octadecylsilane column. The mobile phase consisted of 13% acetonitrile and 0.05% tirfluoroacetic acid in water. Chiralpak QD-AX and KSAACSP-001S enantioselective columns were used in the second dimension to separate LA and 3HB enantiomers, respectively. Mobile phases were mixed solutions of methanol and acetonitrile containing formic acid. The separation factors were 1.14 and 1.08, respectively. The detection limit of LA and 3HB enantiomers was 10 fmol/injection. This method was applied to human clinical samples; intra- and inter-day relative standard deviations of LA and 3HB enantiomers were, respectively, 1.04-3.25% and 1.61-5.12% in plasma, 9.19-11.2% and 4.60-5.89% in urine, and 7.12-8.90% and 2.86-6.97% in saliva. This novel analytical method is a powerful tool for investigating variations in LA and 3HB enantiomers under disease conditions. PMID- 26256242 TI - Metal-coordination-driven mixed ligand binding in supramolecular bisporphyrin tweezers. AB - Mg(II)bisporphyrin has been used as an efficient host for the selective binding of guest ligands. In the presence of heterogeneous guest pairs, 2 aminopyrimidine/pyrazine and 2-aminopyrimidine/1,4-dioxane, 2-aminopyrimidine is bound selectively inside the bisporphyrin cavity whereas pyrazine/1,4-dioxane is bound outside to produce 1D mixed ligand polymers. UV-vis, (1)H NMR spectra and X ray structure confirm such a selective and orthogonal binding of the guest ligands. The mixed ligand polymer has been synthesized just by mixing the host and guests in one pot and easily isolated as a solid in nearly quantitative yield due to its high stability. PMID- 26256243 TI - All-trans retinoic acid modulates the balance of ADAMTS13 and VWF in human microvascular endothelial cells. AB - PURPOSE: To better understand the antithrombotic property of All-trans retinoic acid (ATRA), we investigated whether ATRA may affect the balance between ADAMTS13 and von Willebrand factor (VWF) in human microvascular endothelial cell. METHODS: Compared to tumor necrosis factor-alpha (TNF-alpha), we observed the effects of ATRA on the expression of ADAMTS13 and VWF. ADAMTS13mRNA in human microvascular endothelial cell (HMEC-1 cell line) were detected by real-time polymerase chain reaction amplification (RT-PCR). The levels of ADAMTS13 and VWF antigen were detected by western blot or enzyme-linked immunosorbent assay (ELISA), and the proteolytic activity of ADAMTS13 was also determined by using GST-VWF73-His peptide as a specific substrate. RESULTS: ATRA significantly upregulated the expression of ADAMTS13mRNA in HMEC-1, while TNF-alpha inhibited ADAMTS13mRNA expression. ATRA could reverse the inhibition expression of ADAMTS13 by TNF alpha. The results were confirmed from the levels of ADAMTS13 protein and its activity, while ATRA had no significant affection on triggering release of VWF. CONCLUSIONS: This study provides the evidence that ATRA modulates the balance of ADAMTS13 and VWF in human microvascular endothelial cell, which might be a very relevant compartment for the antithrombotic property of ATRA. PMID- 26256244 TI - A trimetallic strategy towards ZnDyCr and ZnDyCo single-ion magnets. AB - Two cyano- and phenoxo-bridged octanuclear complexes ZnDyCo (complex ) and ZnDyCr (complex ) with diamagnetic Zn(ii) and Co(iii) are reported. Dy(iii) is surrounded by nine oxygen atoms of two [Zn(Me2valpn)] (Me2valpn(2-) = dianion of N,N'-2,2-dimethylpropylenebis(3-methoxysalicylideneimine)) and one water molecule. Magnetic studies reveal that both exhibit single-ion magnet (SIM) behavior with the energy barrier of 85.9 K for complex and 100.9 K for complex . PMID- 26256245 TI - Crystal structure of the first WW domain of human YAP2 isoform. AB - The WW domains are the smallest modular domains known. The study of the structural basis of their stability is important to understand their physiological role. These domains are intrinsically flexible, which makes them difficult to crystallize. The first WW domain of the human Yes tyrosine kinase Associated Protein (YAP) has been crystallized and its structure has been solved by X-ray diffraction at 1.6 A resolution. Crystals belong to the orthorhombic space group P21212 with unit cell parameters a=42.67, b=43.10 and c=21.30. The addition of proline and other small-molecule additives improves drastically the quality of the crystals. The interactions that stabilize this minimal modular domain have been analysed. This crystal structure reveals that, besides the stabilization of the hydrophobic core of the protein by the aromatic cluster formed by Trp177-Phe189-Pro202, some salt-bridges interactions might affect the stability of the domain. PMID- 26256246 TI - Cytosolic BMAL1 moonlights as a translation factor. AB - It is widely recognized that BMAL1 is an essential subunit of the primary transcription factor that drives rhythmic circadian transcription in the nucleus. In a surprising turn, Lipton et al. now show that BMAL1 rhythmically interacts with translational machinery in the cytosol to stimulate protein synthesis in response to mTOR signaling. PMID- 26256247 TI - Comparing methods for ex vivo characterization of human monocyte phenotypes and in vitro responses. AB - Monocytes are key innate effector cells and their phenotype and function may be a useful biomarker of disease state or therapeutic response. However, for such an assay to be clinically feasible it needs to be simple and reproducible, which this study aimed to address. Peripheral blood mononuclear cells (PBMC)(2) isolated from whole blood using Histopaque-1077 or cell preparation tubes (CPT) showed no difference in the ex vivo monocyte activation marker expression or in vitro responses; however, a delayed isolation using CPT significantly altered ex vivo and in vitro phenotypes and responses. Furthermore, purification of monocytes using CD14(+) microbeads resulted in a loss of CD14(low)CD16(+) monocytes compared to PBMC samples. Thus, the use of CPT reduced complexity and time compared to Histopaque, and PBMC isolation allowed the analysis of all 3 major monocyte subsets. Finally, because the delayed isolation of PBMC from CPT significantly altered monocytes, time delays should be standardized. PMID- 26256248 TI - Photocatalytic degradation of the antibiotic chloramphenicol and effluent toxicity effects. AB - Chloramphenicol sodium succinate (CAP, C15H15Cl2N2 Na2O8) is a broad-spectrum antibiotic exhibiting activity against both Gram-positive and Gram-negative bacteria as well as other groups of microorganisms only partially removed by conventional activated sludge wastewater treatment plants. Thus, CAP and its metabolites can be found in effluents. The present work deals with the photocatalytic degradation of CAP using TiO2 as photocatalyst. We investigated the optimization of reaction contact time and concentration of TiO2 considering CAP and its by-products removal as well as effluent ecotoxicity elimination. Considering a CAP real concentration of 25mgL(-1), kinetic degradation curves were determined at 0.1, 0.2, 0.4, 0.8, 1.6 and 3.2gL(-1) TiO2 after 5, 10, 30, 60 and 120min reaction time. Treated samples were checked for the presence of by products and residual toxicity (V. fischeri, P. subcapitata, L. sativum and D. magna). Results evidenced that the best combination for CAP and its by-products removal could be set at 1.6gL(-1) of TiO2 for 120min with an average residual toxicity of approximately 10%, that is the threshold set for negative controls in most toxicity tests for blank and general toxicity test acceptability. PMID- 26256249 TI - Improving the performance and emission characteristics of a single cylinder diesel engine having reentrant combustion chamber using diesel and Jatropha methyl esters. AB - The emissions from the Compression ignition (CI) engines introduce toxicity to the atmosphere. The undesirable carbon deposits from these engines are realized in the nearby static or dynamic systems such as vehicles, inhabitants, etc. The objective of this research work is to improve the performance and emission characteristics of a diesel engine in the modified re-entrant combustion chamber using a diesel and Jatropha methyl ester blend (J20) at three different injection pressures. From the literature, it is revealed that the shape of the combustion chamber and the fuel injection pressure have an impact on the performance and emission parameters of the CI engine. In this work, a re-entrant combustion chamber with three different fuel injection pressures (200, 220 and 240bars) has been used in the place of the conventional hemispherical combustion chamber for diesel and J20. From the experimental results, it is found that the re-entrant chamber improves the brake thermal efficiency of diesel and J20 in all the tested conditions. It is also found that the 20% blend of Jatropha methyl ester showed 4% improvement in the brake thermal efficiency in the re-entrant chamber at the maximum injection pressure. Environmental safety directly relates to the reduction in the undesirable effects on both living and non-living things. Currently environmental pollution is of major concern. Even with the stringent emission norms new methods are required to reduce the harmful effects from automobiles. The toxicity of carbon monoxide (CO) is well known. In the re entrant combustion chamber, the amount of CO emission is reduced by 26% when compared with the conventional fuel operation of the engine. Moreover, the amount of smoke is reduced by 24% and hydrocarbons (HC) emission by 24%. Thus, the modified re-entrant combustion chamber reduces harmful pollutants such as unburned HC and CO as well as toxic smoke emissions. PMID- 26256250 TI - An acellular biologic scaffold does not regenerate appreciable de novo muscle tissue in rat models of volumetric muscle loss injury. AB - Extracellular matrix (ECM) derived scaffolds continue to be investigated for the treatment of volumetric muscle loss (VML) injuries. Clinically, ECM scaffolds have been used for lower extremity VML repair; in particular, MatriStemTM, a porcine urinary bladder matrix (UBM), has shown improved functional outcomes and vascularization, but limited myogenesis. However, efficacy of the scaffold for the repair of traumatic muscle injuries has not been examined systematically. In this study, we demonstrate that the porcine UBM scaffold when used to repair a rodent gastrocnemius musculotendinous junction (MTJ) and tibialis anterior (TA) VML injury does not support muscle tissue regeneration. In the MTJ model, the scaffold was completely resorbed without tissue remodeling, suggesting that the scaffold may not be suitable for the clinical repair of muscle-tendon injuries. In the TA VML injury, the scaffold remodeled into a fibrotic tissue and showed functional improvement, but not due to muscle fiber regeneration. The inclusion of physical rehabilitation also did not improve functional response or tissue remodeling. We conclude that the porcine UBM scaffold when used to treat VML injuries may hasten the functional recovery through the mechanism of scaffold mediated functional fibrosis. Thus for appreciable muscle regeneration, repair strategies that incorporate myogenic cells, vasculogenic accelerant and a myoconductive scaffold need to be developed. PMID- 26256251 TI - P50: A candidate ERP biomarker of prodromal Alzheimer's disease. AB - INTRODUCTION: Reductions of cerebrospinal fluid (CSF) amyloid-beta (Abeta42) and elevated phosphorylated-tau (p-Tau) reflect in vivo Alzheimer's disease (AD) pathology and show utility in predicting conversion from mild cognitive impairment (MCI) to dementia. We investigated the P50 event-related potential component as a noninvasive biomarker of AD pathology in non-demented elderly. METHODS: 36 MCI patients were stratified into amyloid positive (MCI-AD, n=17) and negative (MCI-Other, n=19) groups using CSF levels of Abeta42. All amyloid positive patients were also p-Tau positive. P50s were elicited with an auditory oddball paradigm. RESULTS: MCI-AD patients yielded larger P50s than MCI-Other. The best amyloid-status predictor model showed 94.7% sensitivity, 94.1% specificity and 94.4% total accuracy. DISCUSSION: P50 predicted amyloid status in MCI patients, thereby showing a relationship with AD pathology versus MCI from another etiology. The P50 may have clinical utility for inexpensive pre-screening and assessment of Alzheimer's pathology. PMID- 26256253 TI - Resisting false recognition: An ERP study of lure discrimination. AB - There is keen interest in what enables rememberers to differentiate true from false memories and which strategies are likely to be the most effective. This study measured electrical brain activity while healthy young adults performed a mnemonic discrimination task, deciding whether color pictures had been studied, were similar to studied pictures (lures), or were new. Between 500 and 800 ms post-stimulus, event-related potentials (ERPs) for correctly recognized studied pictures and falsely recognized lures compared to those for correctly rejected novel items had a left centroparietal scalp distribution. This was typical of the parietal old/new effect associated with recollection, and in line with previous evidence that similar lures may elicit false or phantom recollection as opposed to just familiarity. There was no evidence of a parietal effect for correctly rejected lures as would be expected if recall-to-reject was used. The ERP old/new effects for lures also varied with individual differences in performance. Parietal effects for falsely recognized lures were larger in better performers, who successfully rejected a greater number of lures as "similar". The better performers also showed more pronounced right frontocentral old/new effects between 800 and 1100 ms for correctly rejected and falsely recognized similar lures. The enhancement of false recollection in better performers implies false recognition of lures occurred only when more specific information was recovered about the study episodic. Together, the findings suggest reliance on recollection to decide that items were studied, supported by post-retrieval processing. PMID- 26256252 TI - Metabotropic glutamate receptor 5 upregulates surface NMDA receptor expression in striatal neurons via CaMKII. AB - Metabotropic and ionotropic glutamate receptors are closely clustered in postsynaptic membranes and are believed to interact actively with each other to control excitatory synaptic transmission. Metabotropic glutamate receptor 5 (mGluR5), for example, has been well documented to potentiate ionotropic NMDA receptor activity, although underlying mechanisms are poorly understood. In this study, we investigated the role of mGluR5 in regulating trafficking and subcellular distribution of NMDA receptors in adult rat striatal neurons. We found that the mGluR1/5 agonist DHPG concentration-dependently increased NMDA receptor GluN1 and GluN2B subunit expression in the surface membrane. Meanwhile, DHPG reduced GluN1 and GluN2B levels in the intracellular compartment. The effect of DHPG was blocked by an mGluR5 selective antagonist MTEP but not by an mGluR1 selective antagonist 3-MATIDA. Pretreatment with an inhibitor or a specific inhibitory peptide for synapse-enriched Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) also blocked the DHPG-stimulated redistribution of GluN1 and GluN2B. In addition, DHPG enhanced CaMKIIalpha activity and elevated GluN2B phosphorylation at a CaMKII-sensitive site (serine 1303). These results demonstrate that mGluR5 regulates trafficking of NMDA receptors in striatal neurons. Activation of mGluR5 appears to induce rapid trafficking of GluN1 and GluN2B to surface membranes through a signaling pathway involving CaMKII. PMID- 26256254 TI - Exposure to prenatal stress has deleterious effects on hippocampal function in a febrile seizure rat model. AB - Prenatal stress has been shown to result in the development of a number of neurological disorders in the offspring. Most of these disorders are a result of an altered HPA axis resulting in higher than normal glucocorticoid levels in the affected neonate. This leaves the offspring prone to immune challenges. Therefore the aim of the present study was to investigate the effects of prenatal stress and febrile seizures on behavior and hippocampal function. Pregnant dams were exposed to restraint stress during the third trimester. Following birth, febrile seizures were induced in two week old pups using lipopolysaccharide and kainic acid. A week later, anxiety-like behavior and navigational ability was assessed. Trunk blood was used to measure basal corticosterone concentration and hippocampal tissue was collected and analyzed. Our results show that exposure to prenatal stress increased basal corticosterone concentration. Exposure to prenatal stress exacerbated anxiety-like behavior and impaired the rat's navigational ability. Exposure to prenatal stress resulted in reduced hippocampal mass that was exacerbated by febrile seizures. However, exposure to febrile seizures did not affect hippocampal mass in the absence of prenatal stress. This suggests that febrile seizures are exacerbated by exposure to early life stressors and this may lead to the development of neurological symptoms associated with a malfunctioning hippocampus. PMID- 26256255 TI - [Experience with the use of the bio-active stent coated with titanium nitric oxide compared with zotarolimus-eluting stent: experience of a unit medical high specialty]. AB - The use of coronary stents in coronary angioplasty has evolved dramatically in its design, type materials, polymers, and a variety of drugs, the use of coronary stents covered nitric oxide have shown satisfactory results in practice, however compared to the results reported drug-eluting stents, there is little information. OBJECTIVES: The aim of this study was to compare clinical outcomes of a stainless steel stent Bioactive nitric oxide coated titanium (BAS) and a drug-eluting stent zotarolimus (DES) in daily clinical practice. METHODS: A retrospective, analytical, descriptive and comparative study aimed at evaluating the safety and efficacy of two devices with different characteristics in our population. The primary endpoints were: death, acute infarction (AMI), and re intervention injury Treated (RLT). RESULTS: A total of 759 patients were included in the study which was performed angioplasty to a single vessel. Were divided into two arms 382 with DES and 377 patients with BAS, the one year follow up was carried in 95%. After this follow-up period, primary points (cardiovascular death, myocardial infarction, TLR and stent thrombosis) for arm DES vs BAS; 9.5% vs 8.5% P=NS but with shorter periods of dual antiplatelet therapy for arm BAS 6.9+/-4.1 vs 11.1+/-2.5 months DES P=.0001. The results were independent of the clinical syndrome of presentation. CONCLUSIONS: After one year of follow no statistically significant difference in major clinical events, there was a trend in favour of BAS vs SM with respect to revascularization of the target lesion without reaching statistical significance. PMID- 26256256 TI - [Prehospital thrombolysis: A national perspective. Pharmaco-invasive strategy for early reperfusion of STEMI in Mexico]. AB - OBJECTIVE: To review the existing evidence on the role of prehospital thrombolysis in patients with ST-segment elevation acute myocardial infarction (STEMI) as part of a strategy of cutting edge to reduce the time of coronary reperfusion and as a consequence improves both the survival and function. METHODS: We used the technique of exploration-reduction-evaluation-analysis and synthesis of related studies, with an overview of current recommendations, data from controlled clinical trials and from the national and international registries about the different strategies for STEMI reperfusion. In total, we examined 186 references on prehospital thrombolysis, 130 references in times door treatment, 139 references in STEMI management and national and international registries as well as 135 references on rescue and primary percutaneous coronary intervention for STEMI. Finally the 48 references that were more relevant and informative were retained. CONCLUSION: The "time" factor is crucial in the success of early reperfusion in STEMI especially if thrombolysis is applied correctly during the prehospital time. The primary percutaneous coronary intervention is contingent upon its feasibility before 120 min from the onset of symptoms. In our midst to internationally, thrombolysis continues to be a strategy with great impact on their expectations of life and function of patients. Telecommunication systems should be incorporate in real time to the priority needs of catastrophic diseases such as STEMI where life is depending on time. PMID- 26256257 TI - Serum YKL-40 as a Marker of Left Atrial Fibrosis Assessed by Delayed Enhancement MRI in Lone Atrial Fibrillation. AB - BACKGROUND: Assessment of the left atrial (LA) fibrosis by using delayed-enhanced magnetic resonance imaging (DE-MRI) in atrial fibrillation (AF) patients is a pioneering noninvasive method. Serum YKL-40 is a novel marker for inflammation and known to play a role in ongoing tissue fibrosis. However, its role in LA fibrosis is unclear. We aimed to investigate the association of serum YKL-40 with the presence and extent of LA fibrosis. METHODS: A total of 50 patients with lone paroxysmal AF (62% male; age: 47.2 +/- 7.0 years) underwent cardiac DE-MRI according to study protocol. Cardiac DE-MRI at 1.5 Tesla scanner was used to quantify LA fibrosis. Serum YKL-40 levels and clinical and echocardiographic data were recorded in all participants. RESULTS: DE-MRI revealed any degree of LA fibrosis in 31 (62%) patients. Median serum YKL-40 was significantly higher (P = 0.008) and left venticular ejection fraction was lower (P = 0.047) in patients with LA fibrosis as compared to patients without LA fibrosis. Extent of LA fibrosis was significantly correlated with age, duration of AF history, serum C reactive protein, and serum YKL-40 levels. Only log (YKL-40) level was found as independent predictor for the presence of LA fibrosis (odds ratio: 1.626, P = 0.022). Multivariate linear regression analysis pointed out that duration of AF history (beta = 0.330, P = 0.003) and serum log (YKL-40) levels (beta = 0.546, P < 0.001) were significantly and independently associated with the extent of LA fibrosis. CONCLUSION: Higher levels of serum YKL-40 are associated with the presence and more extensive LA fibrosis in patients with lone AF. As a marker of inflammation, serum YKL-40 may also be used as an indicator for the degree of LA fibrosis. PMID- 26256258 TI - Increased Butyrate Production During Long-Term Fermentation of In Vitro-Digested High Amylose Cornstarch Residues with Human Feces. AB - An in vitro semi-continuous long-term (3 wk) anaerobic incubation system simulating lower gut fermentation was used to determine variability in gut microbial metabolism between 4 predigested high amylose-resistant starch residues (SR): SRV, SRVI, SRVII, and SRGEMS in human fecal samples. Subjects participated twice, 5 mo apart: 30 in Phase I (15 lean, 9 overweight and 6 obese), 29 in Phase II (15 lean, 9 overweight, 5 obese); 13 of 15 lean subjects participated in both phases. Of the 4 SRs, SRV displayed the highest gelatinization temperature, peak temperature, enthalpy changes, and the least digestibility compared with the other SRs. In both phases, compared with blank controls, all SRs increased butyrate ~2-fold which stabilized at week 2 and only SRV caused greater propionate concentration (~30%) after 3 wk which might have been partly mediated by its lesser digestibility. Fecal samples from lean and overweight/obese subjects incubated with SRs showed similar short-chain fatty acid production across both time points, which suggests that resistant starch may benefit individuals across BMIs. PMID- 26256259 TI - Dual-targeting nanocarrier system based on thermosensitive liposomes and gold nanorods for cancer thermo-chemotherapy. AB - The primary challenge of cancer therapy was the failure of most chemotherapeutics to accumulate in the tumors, additionally causing serious systemic side effects. We designed a tumor-targeting accumulated and locally triggered-release nanocarrier system to increase the intratumoral drug concentration and thus the efficacy of chemotherapy, based on gold nanorods (GNRs) and thermosensitive liposomes (TSLs). PEGylated GNRs could not only make nanocarriers to co accumulate in tumors depending on enhanced permeability and retention (EPR) effect, but also generated heat locally under near-infrared (NIR) stimulation. CO2 bubbles were generated by the encapsulated ammonium bicarbonate (ABC) under hyperthermia, thus the co-encapsulated drug was released and local drug concentration was increased along with the disintegration of liposomal membrane. On the other hand, this dual-targeting system prevented the drug leakage in blood circulation or other organs while facilitated most of the active agents delivered to tumors. In vitro and in vivo experiments revealed high cytotoxicity and good affinity of HTSL to MDA-MB-435 cells when used synergistically with GNRs, but low toxicity to normal cells at the same condition. When combined with thermotherapy, the smart nanocarrier system held significant promise for future cancer treatment for their markedly improved therapeutic efficacy and decreased systemic toxicity. PMID- 26256261 TI - Effects of the properties of short peptides conjugated with cell-penetrating peptides on their internalization into cells. AB - Peptides, especially intracellular functional peptides that can play a particular role inside a cell, have attracted attention as promising materials to control cell fate. However, hydrophilic materials like peptides are difficult for cells to internalize. Therefore, the screening and design of intracellular functional peptides are more difficult than that of extracellular ones. An effective high throughput screening system for intracellular functional peptides has not been reported. Here, we demonstrate a novel peptide array system for screening intracellular functional peptides, in which both cell-penetrating peptide (CPP) domain and photo-cleavable linkers are used. By using this screening system, we determined how the cellular uptake properties of CPP-conjugated peptides varied depending on the properties of the conjugated peptides. We found that the internalization ability of CPP-conjugated peptides varied greatly depending on the property of the conjugated peptides, and anionic peptides drastically decreased the uptake ability. We summarized our data in a scatter diagram that plots hydrophobicity versus isoelectric point (pI) of conjugated peptides. These results define a peptide library suitable for screening of intracellular functional peptides. Thus, our system, including the diagram, is a promising tool for searching biological active molecules such as peptide-based drugs. PMID- 26256260 TI - Small molecules targeting microRNA for cancer therapy: Promises and obstacles. AB - Aberrant expression of miRNAs is critically implicated in cancer initiation and progression. Therapeutic approaches focused on regulating miRNAs are therefore a promising approach for treating cancer. Antisense oligonucleotides, miRNA sponges, and CRISPR/Cas9 genome editing systems are being investigated as tools for regulating miRNAs. Despite the accruing insights in the use of these tools, delivery concerns have mitigated clinical application of such systems. In contrast, little attention has been given to the potential of small molecules to modulate miRNA expression for cancer therapy. In these years, many researches proved that small molecules targeting cancer-related miRNAs might have greater potential for cancer treatment. Small molecules targeting cancer related miRNAs showed significantly promising results in different cancer models. However, there are still several obstacles hindering the progress and clinical application in this area. This review discusses the development, mechanisms and application of small molecules for modulating oncogenic miRNAs (oncomiRs). Attention has also been given to screening technologies and perspectives aimed to facilitate clinical translation for small molecule-based miRNA therapeutics. PMID- 26256262 TI - Preparation and evaluation of lipid emulsified docetaxel-loaded nanoparticles. AB - OBJECTIVES: Lipid emulsified nanoparticles (LPNPs) have been developed to load anticancer drug docetaxel (DTX) in this work. METHODS: We evaluated DTX-loaded lipid emulsified nanoparticles (DTX-LPNPs) in vitro compared with the conventional nanoparticles (DTX-NPs). The newly developed formulation was compared with DTX-NPs in terms of physicochemical properties and in-vitro efficacy. KEY FINDINGS: These two formulations had similar physicochemical properties in our results. And it has been proven that phosphatidylethanolamine had higher emulsification efficiency (20-fold of polyvinyl alcohol) in the same preparation procedure. The in-vitro release of DTX from DTX-LPNPs showed burst release initially and then followed by a sustained release, which prolonged the half time. The cytotoxicity test indicated that the DTX-LPNPs were more effective against tumour growth, and the IC50 of Duopafei, DTX-NPs and DTX-LPNPs for the inhibition of human lung cancer A549 cells at 48 h (n = 3) were found to be 3.53 +/- 0.43, 1.15 +/- 0.06 and 0.55 +/- 0.08 MUm, respectively. The evaluation of the cellular uptake showed that DTX-LPNPs improved the drug delivery into cytoplasm compared with the commercial product Duopafei and DTX-NPs. CONCLUSIONS: DTX-LPNPs may be a promising formulation for cancer therapy. PMID- 26256263 TI - The Chronic Obstructive Sialadenitis Symptoms Questionnaire to assess sialendoscopy-assisted surgery. AB - OBJECTIVES/HYPOTHESIS: Introduce the Chronic Obstructive Sialadenitis Symptoms (COSS) questionnaire to quantify chronic sialadenitis symptoms and assess the impact of sialendoscopic-assisted salivary duct surgery (SASDS). STUDY DESIGN: Retrospective outcome symptoms questionnaire study. METHODS: The COSS questionnaire assesses the severity of sialadenitis symptoms from 0 to 100. Patients who underwent SASDS from April 2006 to December 2013 completed the COSS questionnaire and the ShortForm8 Health Survey (SF-8) based on current symptoms, and reported whether they had complete, partial, or no symptomatic response to SASDS. RESULTS: Sixty-six of the 156 (43%) contacted patients completed the questionnaires who had had symptoms in 26 submandibular ducts and 53 parotid ducts. The mean COSS score was higher for parotid ducts (12.0; interquartile range [IQR] 1.0-20.0) than for submandibular ducts (7.6; IQR 0.5-15.0) but not significantly so (P = 0.20). Thirty-eight (60%) patients reported complete resolution of symptoms, with a mean COSS score of 4.5 (IQR 0-7). Twenty-one (33%) patients reported partial resolution, with a mean COSS score of 18.5 (IQR 11.3 22.8). Five (8%) patients reported no improvement, with a mean COSS score of 25.1 (IQR 15.2-35). Thirty-six (46%) ducts with sialoliths had a significantly lower mean COSS score (5.8; IQR 0-9.5) compared to those without sialoliths (14.2; IQR 4.5-21.5, P = 0.0004). There was no significant difference in SF-8 survey scores between these groups. CONCLUSION: The COSS questionnaire is a novel survey instrument to measure obstructive sialadenitis symptom severity that could be helpful in defining outcomes of SASDS. COSS scores under 10 correlate with complete resolution of symptoms, whereas scores between 10 and 25 correlate with partial resolution. PMID- 26256264 TI - Fetal limb soft tissue assessment for prediction of birth weight and umbilical cord blood analytes in gestational diabetes. AB - OBJECTIVE: To evaluate the value of third trimester ultrasound (estimated fetal weight, cheek-to-cheek diameter, sectional Wharton's jelly area, sectional areas and fractional volumes in extremities) to predict birth weight and cord biochemical markers at birth (leptin, insulin, c-peptide, IGF1, erythropoietin and ferritin) in diabetic pregnancies. METHOD: Prospective study in 49 patients with gestational diabetes. An ultrasound was performed between 32 and 34 weeks. Clinical data were collected, and a blood sample was obtained from cord after birth. ROC curve models were evaluated for 75(th) and 90(th) birth weight percentile. Univariate and multivariate models were used to assess the association between ultrasound and neonatal outcomes. RESULTS: Sectional areas and fractional volumes showed significant differences and highest AUC values for predicting birth weight. A significant association was found for extremities measurements with total birth weight and its percentile. The only marker which showed a significant association to estimated fetal weight was erythropoietin. Sectional areas and fractional volumes related to cord leptin, erythropoietin, insulin and c-peptide. CONCLUSION: Sectional areas and fractional volumes improve the predictive value of estimated fetal weight in diabetic pregnancies. They also show a predictive association to biochemical changes in cord (leptin, insulin and erythropoietin) related to increased adiposity and risk of fetal hypoxia. (c) 2015 John Wiley & Sons, Ltd. PMID- 26256265 TI - Activated mast cells synthesize and release soluble ST2-a decoy receptor for IL 33. AB - IL-33 released from damaged cells plays a central role in allergic inflammation by acting through its membrane-bound receptor, ST2 receptor (ST2L). IL-33 activity can be neutralized by the soluble spliced variant of ST2 (sST2) that has been associated with allergic inflammation but its source is not well defined. We investigated whether mast cells (MCs) are a significant source of sST2 following activation through FcepsilonRI or ST2. We find that antigen and IL-33 induce substantial production and release of sST2 from human and mouse MCs in culture and do so synergistically when added together or in combination with stem cell factor. Moreover, increases in circulating sST2 during anaphylaxis in mice were dependent on the presence of MCs. Human MCs activated via FcepsilonRI failed to generate IL-33 and IL-33 produced by mouse bone marrow-derived MCs was retained within the cells. Therefore, FcepsilonRI-mediated sST2 production is independent of MC-derived IL-33 acting in an autocrine manner. These results are consistent with the conclusion that both mouse and human MCs when activated are a significant inducible source of sST2 but not IL-33 and thus have the ability to modulate the biologic impact of IL-33 produced locally by other cell types during allergic inflammation. PMID- 26256266 TI - High temperature attenuates the gravitropism of inflorescence stems by inducing SHOOT GRAVITROPISM 5 alternative splicing in Arabidopsis. AB - In higher plants, gravitropism proceeds through three sequential steps in the responding organs: perception of gravity signals, signal transduction and asymmetric cell elongation. Light and temperature also influence the gravitropic orientation of plant organs. A series of Arabidopsis shoot gravitropism (sgr) mutants has been shown to exhibit disturbed shoot gravitropism. SGR5 is functionally distinct from other SGR members in that it mediates the early events of gravitropic responses in inflorescence stems. Here, we demonstrated that SGR5 alternative splicing produces two protein variants (SGR5alpha and SGR5beta) in modulating the gravitropic response of inflorescence stems at high temperatures. SGR5beta inhibits SGR5alpha function by forming non-DNA-binding heterodimers. Transgenic plants overexpressing SGR5beta (35S:SGR5beta) exhibit reduced gravitropic growth of inflorescence stems, as observed in the SGR5-deficient sgr5 5 mutant. Interestingly, SGR5 alternative splicing is accelerated at high temperatures, resulting in the high-level accumulation of SGR5beta transcripts. When plants were exposed to high temperatures, whereas gravitropic curvature was reduced in Col-0 inflorescence stems, it was uninfluenced in the inflorescence stems of 35S:SGR5beta transgenic plants and sgr5-5 mutant. We propose that the thermoresponsive alternative splicing of SGR5 provides an adaptation strategy by which plants protect the shoots from hot air under high temperature stress in natural habitats. PMID- 26256267 TI - Integrated Proteomic and Glycoproteomic Analyses of Prostate Cancer Cells Reveal Glycoprotein Alteration in Protein Abundance and Glycosylation. AB - Prostate cancer is the most common cancer among men in the U.S. and worldwide, and androgen-deprivation therapy remains the principal treatment for patients. Although a majority of patients initially respond to androgen-deprivation therapy, most will eventually develop castration resistance. An increased understanding of the mechanisms that underline the pathogenesis of castration resistance is therefore needed to develop novel therapeutics. LNCaP and PC3 prostate cancer cell lines are models for androgen-dependence and androgen independence, respectively. Herein, we report the comparative analysis of these two prostate cancer cell lines using integrated global proteomics and glycoproteomics. Global proteome profiling of the cell lines using isobaric tags for relative and absolute quantitation (iTRAQ) labeling and two- dimensional (2D) liquid chromatography-tandem MS (LC-MS/MS) led to the quantification of 8063 proteins. To analyze the glycoproteins, glycosite-containing peptides were isolated from the same iTRAQ-labeled peptides from the cell lines using solid phase extraction followed by LC-MS/MS analysis. Among the 1810 unique N-linked glycosite-containing peptides from 653 identified N-glycoproteins, 176 glycoproteins were observed to be different between the two cell lines. A majority of the altered glycoproteins were also observed with changes in their global protein expression levels. However, alterations in 21 differentially expressed glycoproteins showed no change at the protein abundance level, indicating that the glycosylation site occupancy was different between the two cell lines. To determine the glycosylation heterogeneity at specific glycosylation sites, we further identified and quantified 1145 N-linked glycopeptides with attached glycans in the same iTRAQ-labeled samples. These intact glycopeptides contained 67 glycan compositions and showed increased fucosylation in PC3 cells in several of the examined glycosylation sites. The increase in fucosylation could be caused by the detected changes in enzymes belonging to the glycan biosynthesis pathways of protein fucosylation observed in our proteomic analysis. The altered protein fucosylation forms have great potential in aiding our understanding of castration resistance and may lead to the development of novel therapeutic approaches and specific detection strategies for prostate cancer. PMID- 26256268 TI - The Dependence of Amyloid-beta Dynamics on Protein Force Fields and Water Models. AB - We studied the dynamics of Abeta40 , involved in Alzheimer's disease, by using 21 methods combined from Amber03, Amber99sb-ILDN, Charmm27, Charmm22*, OPLS-2001, OPLS-2006, OPLS-2008, Gromos96-43a1, Gromos96-53a6, Gromos96-54a7, and the water models SPC, TIP3P, TIP4P. Major differences in the structural ensembles were systematized: Amber03, Charmm27, and Gromos96-54a7 stabilize the helices; Gromos96-43a1 and Gromos53a6 favor the beta-strands (with Charmm22* and Amber99sb ILDN in between), and OPLS produces unstructured ensembles. The accuracy of the NMR chemical shifts was in the order: Charmm22*>Amber99sb-ILDN>OPLS-2008~Gromos96 43a1>Gromos96-54a7~OPLS-2001>OPLS-2006>Gromos96-53a6>Charmm27>Amber03. The computed (3) JHNHalpha -coupling constants were sensitive to experiment type and Karplus parameterization. Overall, the ensembles of Charmm22* and Amber99sb-ILDN provided the best agreement with experimental NMR and circular dichroism data, providing a model for the real Abeta monomer ensemble. Also, the polar water model TIP3P significantly favored helix and compact conformations. PMID- 26256269 TI - Radiation therapy for people with cancer: what do written information materials tell them? AB - This study aimed to compare and contrast the contents of different types of written patient information about radiotherapy, namely (1) hospital radiotherapy departments vs. cancer control organisations and (2) generic vs. tumour-specific materials. A coding framework, informed by existing patients' information needs literature, was developed and applied to 54 radiotherapy information resources. The framework comprised 12 broad themes; cancer diagnosis, general information about radiotherapy, treatment planning, daily treatment, side effects, self-care management, external radiotherapy, internal radiotherapy, impact on daily activities, post-treatment, psychosocial health and other content, such as a glossary. Materials produced by cancer organisations contained significantly more information than hospital resources on diagnosis, general radiotherapy information, internal radiotherapy and psychosocial health. However, hospital materials provided more information about treatment planning, daily treatment and the impact on daily activities. Compared to generic materials, tumour-specific resources were superior in providing information about diagnosis, daily treatment, side effects, post-treatment and psychosocial health. Information about internal radiotherapy, prognosis and chronic side effects were poorly covered by most resources. Collectively, hospital and cancer organisation resources complement each other in meeting patients' information needs. Identifying ways to consolidate different information sources could help comprehensively address patients' medical and psychosocial information needs about radiotherapy. PMID- 26256270 TI - The clinical significance of the pollen calendar of the Western Thrace/northeast Greece region in allergic rhinitis. AB - BACKGROUND: There are major differences in the clinical pattern of allergic rhinitis (AR) patients among countries, reflecting local aerobiological conditions. We analyzed the correlation between airborne pollen concentrations of the Western Thrace/northeast (NE) Greece region with symptoms scores in AR patients. The above data is the first provided for the Mediterranean climate of Greece and reflects the clinical significance of pollen calendar in everyday clinical practice. METHODS: An annual pollen calendar of the most important outdoor aeroallergens (grasses, trees, and weeds) was developed, using a Burkard volumetric spore trap. A total of 168 AR patients were studied and asked to evaluate their symptoms and main seasonal appearance. Sensitization prevalence to pollen species was detected by skin prick tests. Symptoms were evaluated by Total 5 Symptoms Score (T5SS) and correlated to aerobiological data. RESULTS: As far as the pollen calendar is concerned, the highest total percentages of pollens were recorded for olive (24.02% of total), oak (13.74%), grasses (9.08%), and cypress (7.63%). Regarding patients' sensitivities, the most prevalent ones were to grasses (56.0%), olive (43.5%), wall pellitory (24.4%), and cypress (16.7%) antigens. A strong significant correlation between total pollen counts and patients' T5SS (r = 0.874, p < 0.001) was observed. Moreover, strong significant correlations between T5SS and pollen counts were also found for the most prevalent species, including grasses, olive, and Parietaria allergens (r = 0.627, p = 0.029; r = 0.695, p = 0.012; and r = 0.656, p = 0.021, respectively). CONCLUSION: Patients' symptoms scores were found to be significantly correlated to pollen counts. Given data are important for the management of AR patients who live in similar Mediterranean climate conditions. PMID- 26256271 TI - A novel liposomal drug delivery system for PMMA bone cements. AB - The population in developed countries is ageing and the number of people experiencing joint-related conditions, such as osteoarthritis, is expected to increase. Joint replacements are currently the most effective treatment for severe joint conditions and although many of these procedures are successful, infection developing after the procedure is still an issue, requiring complex and expensive revisions. Whilst incorporating a powdered antibiotic within the bone cement can reduce infection rates, the powder frequently agglomerates, resulting in poor antibiotic release characteristics and compromised mechanical performance of the cement. To overcome these issues, a novel delivery system consisting of antibiotic-loaded nano-sized liposomes was developed for inclusion into polymethyl methacrylate (PMMA) bone cement. This system was tested in a commercial cement (Palacos R) and consistently delivered a higher percentage (22%) of the incorporated antibiotic when compared to the powdered antibiotic cement (9%), meaning less antibiotic needs to be incorporated than with conventional cement. The novel system resulted in a controlled and gradual release of antibiotic over a longer, 30-day period and enhanced the toughness, bending strength and Vickers hardness of the cement, without altering its polymerization or molecular structure. This new material has the potential to significantly reduce infections in cemented joint replacements leading to enhanced patient quality of life and reduced healthcare costs. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1510-1524, 2016. PMID- 26256272 TI - Determination of pKa values of some novel benzimidazole salts by using a new approach with (1)H NMR spectroscopy. AB - Benzimidazoles and their derivatives including imidazole are studied widely because they exist in the structure of natural products and different drugs. pKa values are extremely important for drug discovery and improvement in order to determine pharmacokinetic and pharmacodynamic features such as permeation through biological barriers, interactions with the target area or side effects. Acid-base features (pKa ) have great importance not only for physiological characteristics but also for being used as a ligand or changing physico-chemical features by turning benzimidazoles into salts. Within the scope of this study, a variety of new benzimidazole salts were synthesized, and their characterizations were made by NMR spectroscopy, FTIR spectroscopy and element analysis techniques. The pKa values of synthesized benzimidazole salts were determined by inflection point approach using integration values obtained with (1) H NMR spectroscopy and Henderson-Hasselbalch analysis. pKa values of some benzimidazole salts were also determined by potentiometric methods in order to compare those of NMR spectroscopy results. PMID- 26256273 TI - Functional connectivity changes related to cognitive and motor performance in spinocerebellar ataxia type 2. AB - BACKGROUND: Several neuropathological studies in spinocerebellar ataxia type 2 (SCA2) have revealed significant atrophy of the cerebellum, brainstem, sensorimotor cortex, and several regions in the frontal lobe. However, the impact of the neurodegeneration on the functional integration of the remaining tissue is unknown. To analyze the clinical impact of these functional changes, we correlated the abnormal functional connectivity found in SCA2 patients with their scores in clinical scales. To obtain the functional connectivity changes, we followed two approaches. In one we used areas with significant cerebellar gray matter atrophy as anchor seeds, and in the other we performed a whole-brain data driven analysis. METHODS: Fourteen genetically confirmed SCA2 patients and aged matched healthy controls participated in the study. Voxel-based morphometry and resting-state functional magnetic resonance imaging (fMRI) were done to analyze structural and functional brain changes. Independent component analysis and dual regression were used for intrinsic network comparison. Significant functional connectivity differences were correlated with the behavioral scores. RESULTS: Seed-based analysis found reduced functional connectivity within the cerebellum and between the cerebellum and frontal/parietal cortices. Cerebellar functional connectivity increases were found with parietal, frontal, and temporal areas. Intrinsic network analysis found a functional decrease in the cerebellar network, and increase in the default-mode and fronto-parietal networks. Further analysis showed significant correlations between clinical scores and the abnormal functional connectivity strength. CONCLUSION: Our findings show significant correlations between functional connectivity changes in key areas affected in SCA2 and these patients' motor and neuropsychological impairments, adding an important insight to our understanding of the pathophysiology of SCA2. PMID- 26256274 TI - The Life Expectancy of People with Intellectual Disabilities in Germany. AB - BACKGROUND: This study presents age group-specific mortality rates and the average life expectancy of people with intellectual disabilities in Germany. METHOD: For two samples from Westphalia-Lippe and Baden-Wuerttemberg, person related data for the years 2007-2009 were analysed. Age group-specific mortality rates were estimated by exponential regression analyses. RESULTS: The average life expectancy of men with intellectual disabilities was 70.9 years in Westphalia-Lippe and 65.3 years in the Baden-Wuerttemberg sample. Women with intellectual disabilities reached a life expectancy of 72.8 years in the Westphalian sample and 69.9 years in Baden-Wuerttemberg. The mortality tables, the crude mortality rates and the standardized mortality rates according to the WHO standard population are reported. CONCLUSION: Comparing the results with other international studies, the trend of increasing life expectancies of people with intellectual disabilities is confirmed. People with intellectual disabilities still have a lower average life expectancy than the general population, partly due to subgroups with low life expectancies. PMID- 26256275 TI - Mortality Rates in the General Irish Population Compared to those with an Intellectual Disability from 2003 to 2012. AB - BACKGROUND: Historically, there has been higher and earlier mortality among people with intellectual disability as compared to the general population, but there have also been methodological problems and differences in the available studies. METHOD: Data were drawn from the 2012 National Intellectual Disability Database and the Census in Ireland. A standardized mortality ratio (SMR) was calculated, as well as average age at death. Ratios and differences were further examined for the influence of age, gender and level of intellectual disability. RESULTS: Mortality in persons with intellectual disability was four times higher and they were, on average, dying 19 years earlier than peers in the general population. Women with intellectual disability were living longer than males with intellectual disability, but differences in survival as compared to the general population were greater for these women. There was little change in average age at death over 10 years, and death was earlier the more severe the level of intellectual disability. DISCUSSION: The use of mortality ratios rather than average age at death alone is recommended, as well as greater standardization in use of data sets including the whole population, given high levels of earlier deaths in people with intellectual disability. PMID- 26256276 TI - Mortality of People with Intellectual Disabilities in England: A Comparison of Data from Existing Sources. AB - BACKGROUND: At present, there is limited statistical information about mortality of people with intellectual disabilities in England. This study explores the data that are currently available. MATERIALS AND METHODS: Four recent sources of data about mortality of people with intellectual disabilities in England are reviewed: the Confidential Inquiry into Premature Deaths of People with intellectual disabilities (CIPOLD); the 2013 Joint Health and Social Care Intellectual Disability Self-assessment Exercise; local registers of people with intellectual disability; and analysis of Cause of Death certificates. RESULTS: Available data confirm that people with intellectual disability have a shorter lifespan and increased risk of early death when compared with the general population. The standardized mortality rate for people with intellectual disabilities is approximately twice that of the general population in England, with little indication of any reduction in this over time. CONCLUSIONS: Comprehensive data about mortality of people with intellectual disabilities that take account of the age and sex distribution of the population are currently lacking in England. Existing data suggest persistent inequalities between people with intellectual disabilities and the general population. There is an urgent need for better monitoring mechanisms and actions to address these. PMID- 26256277 TI - Understanding Information About Mortality Among People with Intellectual and Developmental Disabilities in Canada. AB - BACKGROUND: This paper reviews what is currently known about mortality among Canadians with intellectual and developmental disabilities and describes opportunities for ongoing monitoring. METHODS: In-hospital mortality among adults with intellectual and developmental disabilities in Ontario was examined using hospital data. Mortality was compared between age-, sex- and residence area matched groups of Manitobans with and without intellectual and developmental disabilities using linked administrative data. A retrospective cohort study of mortality among individuals with intellectual and developmental disabilities in a region of Ontario focused on measuring excess mortality and risk factors. FINDINGS: There is evidence of excess mortality in persons with intellectual and developmental disabilities in Canada. Some of the excess is attributable to comorbidities that are more common in this population. Women may have a greater risk of death than men. Excess mortality occurs at all ages but is more pronounced in early life. DISCUSSION: High-quality ongoing monitoring of mortality among individuals with intellectual and developmental disabilities is possible in Canada. Examination of sex differences should be a priority. PMID- 26256278 TI - Molecular analysis of interactions between a PAMAM dendrimer-paclitaxel conjugate and a biomembrane. AB - Understanding the underlying mechanism of nanomedicine-biomembrane interactions is important for the design and optimization of payload delivery systems. This study investigates the interactions between polyamidoamine (PAMAM) dendrimer paclitaxel conjugates and biomembranes using coarse-grained molecular dynamics simulations. We found that acidic conditions (e.g., pH ~ 5) and membrane asymmetry can improve the conjugate penetration. Paclitaxel (PTX) distributions on a G4 PAMAM dendrimer can affect interactions via the penetration mechanism, although they have no significant effect on interactions via the adsorption mechanism. The random distribution of PTX can enhance the ability of PTX molecules to pass through asymmetric membranes. Furthermore, the penetration process becomes more difficult with increasing paclitaxel loading ratios. These results provide molecular insights into the precise translocation mechanism of dendrimer-drug conjugates and thus provide suggestions for drug design and delivery. PMID- 26256279 TI - Evaluation of the Potential Role of Alirocumab in the Management of Hypercholesterolemia in Patients with High-Risk Cardiovascular Disease. AB - A high level of low-density lipoprotein cholesterol (LDL-C) has proved to have a positive correlation with mortality from cardiovascular disease, and it is the key modifiable risk factor for cardiovascular disease. Lowering levels of LDL-C with statins reduces both vascular morbidity and mortality; however, myalgias occur in 10% to 15% of patients, and many patients managed with statins achieve suboptimal levels of LDL-C. The injectable drug alirocumab-the first of a new class of drugs called proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors-is a monoclonal antibody to the PCSK9 gene, which regulates LDL receptor expression and circulating levels of LDL-C. In this review, we evaluated the efficacy and safety of alirocumab and its potential role in the management of patients with high-risk cardiovascular disease. Data were gathered from articles indexed in the PubMed database (2006-April 2015). All English-language, prospective, randomized, double-blinded trials evaluating the efficacy of alirocumab, as a monotherapy or in combination with statins, for treatment of hypercholesterolemia were identified. Five clinical trials were evaluated, and the results from these studies revealed that the use of alirocumab, both as monotherapy or in combination with statins, significantly reduced LDL-C levels. Patients treated with alirocumab, with or without statins, were more likely to achieve LDL-C goals of less than 100 or 70 mg/dl compared with placebo. Despite its ability to lower LDL-C level, one study did not show any antiinflammatory activity (i.e., reduced C-reactive protein level) among patients who received alirocumab; however, more clinical trials will be needed to further assess this effect. Alirocumab also appears to cause regression of plaque. The most commonly reported adverse effect was mild injection-site reaction. With increased odds of statin discontinuation among patients taking high-intensity statins, alirocumab will contribute to atherosclerotic cardiovascular disease risk reduction. However, morbidity and mortality data, as well as long-term safety data, are pending. Therefore, we propose that alirocumab will better serve as an adjuvant therapy for the management of hypercholesterolemia in patients at high risk for cardiovascular events. As with all new promising injectable drugs, cost will also be a key consideration. PMID- 26256280 TI - Learning curves for transfemoral transcatheter aortic valve replacement in the PARTNER-I trial: Technical performance. AB - OBJECTIVES: To assess technical performance learning curves of teams performing transfemoral transcatheter aortic valve replacement (TF-TAVR). BACKGROUND: TF TAVR is a new procedure for treating severe aortic stenosis. The number of cases required for procedural efficiency is unknown. METHODS: In the PARTNER-I trial, 1,521 patients underwent TF-TAVR from 4/2007-2/2012. Learning curve analysis of technical performance metrics was performed using institution-specific patient sequence number, interval between procedures, and institutional trial entry date. Learning curve characteristics were assessed using semi-parametric and parametric mixed-effects models. RESULTS: As patient sequence number increased, average procedure time decreased from 154 to 85 minutes (P < 0.0001), and fluoroscopy time from 28 to 20 minutes (P < 0.0001). Procedure time plateaued at an average of 83 minutes (range 52-140). Procedure time plateau was dynamic during the course of the trial, averaging 25 cases (range 21-52) by its end. The later institutions enrolled in the trial, the shorter the initial procedure time. During the trial, percutaneous rather than surgical access increased from 7.9% to 69%. CONCLUSIONS: Technical performance learning curves exist for TF-TAVR; procedural efficiency increased with experience, with concomitant decreases in radiation and contrast media exposure. The number of cases needed to achieve efficiency decreased progressively, with optimal procedural performance reached after approximately 25 cases for late-entering institutions. Knowledge and experience accumulated by early TF-TAVR institutions were disseminated, shortening the learning curve of late-entering institutions. Technological advances resulting from learning during the trial moved the field from initial conservative surgical cut-down to percutaneous access for most patients. (c) 2015 Wiley Periodicals, Inc. PMID- 26256281 TI - Non-anaemic iron deficiency - a disease looking for recognition of diagnosis: a systematic review. AB - OBJECTIVE: To capture all data meeting a rigid definition of non-anaemic iron deficiency (NAID) and determine whether it is associated with poor outcomes compared with normal iron status and whether iron supplementation improves outcomes in NAID. DESIGN: Systematic review. DATA SOURCES: EMBASE, Medline, Web of Science, clinicaltrials.gov, International Clinical Trials Registry Platform (ICTRP) and Central from database inception to April 2014. ELIGIBILITY CRITERIA: Ferritin <16 MUg/L (<12 MUg/L if age <5 yr) in the absence of anaemia in observational studies or randomised trials. Where populations were deemed to be sufficiently similar, meta-analysis was undertaken. RESULTS: There were 21 studies included. NAID in pregnancy associated with reduction in birthweight (P = 0.028). Iron supplementation in NAID was associated with improvement in objective scores (P = 0.005) and self-rating (P = 0.03) of fatigue. Meta-analysis was limited and, where possible, was not statistically significant including the comparison of NAID with cardiovascular function in adults (VO2max P = 0.21, RERmax P = 0.68), educational attainment in children (P = 0.14), infant mental (P = 0.29) and psychomotor (P = 0.07) development, and iron supplementation in NAID with educational attainment in language (P = 0.31). CONCLUSIONS: There is emerging evidence that NAID is a disease in its own right, deserving of further research in the development of strategies for detection and treatment. PMID- 26256282 TI - Pre-staining of glycoprotein in SDS-PAGE by the synthesis of a new hydrazide derivative. AB - In this study, a new hydrazide derivative (UGF202) was synthesized and introduced as a highly sensitive and selective fluorescent probe to pre-stain glycoproteins in 1D and 2D SDS-PAGE. As low as 0.5-1 ng glycoproteins (transferrin, alpha1-acid glycoprotein, avidin) could be selectively detected, which is comparable to that of Pro-Q Emerald 300 stain, one of the most sensitive and commonly used glycoprotein staining kit. In addition, the specificity of the newly developed method was confirmed by the study of de-glycosylation, glycoproteins affinity enrichment and LC-MS/MS, respectively. According to the results, it is concluded that UGF202 pre-stain can provide an alternative for the visualization of gel separated glycoproteins. PMID- 26256283 TI - Office-Based Tools and Primary Care Visit Communication, Length, and Preventive Service Delivery. AB - BACKGROUND: The use of physician office-based tools such as electronic health records (EHRs), health risk appraisal (HRA) instruments, and written patient reminder lists is encouraged to support efficient, high-quality, patient-centered care. We evaluate the association of exam room use of EHRs, HRA instruments, and self-generated written patient reminder lists with patient-physician communication behaviors, recommended preventive health service delivery, and visit length. RESEARCH METHODS: Observational study of 485 office visits with 64 primary care physicians practicing in a health system serving the Detroit metropolitan area. Study data were obtained from patient surveys, direct observation, office visit audio-recordings, and automated health system records. Outcome measures included visit length in minutes, patient use of active communication behaviors, physician use of supportive talk and partnership building communication behaviors, and percentage of delivered guideline recommended preventive health services for which patients are eligible and due. Simultaneous linear regression models were used to evaluate associations between tool use and outcomes. Adjusted models controlled for patient characteristics, physician characteristics, characteristics of the relationship between the patient and physician, and characteristics of the environment in which the visit took place. RESULTS: Prior to adjusting for other factors, visits in which the EHR was used on average were significantly (p < .05) longer (27.6 vs. 23.8 minutes) and contained fewer preventive services for which patients were eligible and due (56.5 percent vs. 62.7 percent) compared to those without EHR use. Patient written reminder lists were also significantly associated with longer visits (30.0 vs. 26.5 minutes), and less use of physician communication behaviors facilitating patient involvement (2.1 vs. 2.6 occurrences), but more use of active patient communication behaviors (4.4 vs. 2.6). Likewise, HRA use was significantly associated with increased preventive services delivery (62.1 percent vs. 57.0 percent). All relationships remained significant (p > .05) in adjusted models with the exception of that between HRA use and preventive service delivery. DISSEMINATION AND IMPLEMENTATION IMPLICATIONS: Office-based tools intended to facilitate the implementation of desired primary care practice redesign are associated with both positive and negative cost and quality outcomes. Findings highlight the need for monitoring both intended and unintended consequences of office-based tools commonly used in primary care practice redesign. PMID- 26256284 TI - A Prebiotic Synthesis of Pterins. AB - The genesis of life on Earth is a hypothesis of evolutionary science that can be, at least partially, tested experimentally. The prebiotic synthesis of cofactors or coenzymes is a poorly explored issue, likely because their formation under plausible prebiotic conditions is not clear. In this sense, it has been proposed that the cofactors are "molecular fossils" of an early phase of life. In contrast, Eschenmoser and Loewenthal suggested a prebiotic hydrocyanic origin of cofactor building blocks. In the present paper, the formation of a set of pterins from cyanide polymerizations is demonstrated, showing that the main structure of some cofactors can be prebiotically formed. Indeed, it was observed that aqueous aerosols additionally increase the relative composition for pterins in the insoluble NH4CN polymers synthesized. The novel identification of pterins in NH4CN polymers, together with the previous detection of other important biomonomers, indicates that cyanide polymerizations were essential in the early state of prebiotic chemistry. PMID- 26256285 TI - Thoughts on the Retirement of Professor Juan Murube: Author and Editor of Sources in Time. PMID- 26256286 TI - Questions. PMID- 26256287 TI - Induction and contribution of beta platelet-derived growth factor signalling by hepatic stellate cells to liver regeneration after partial hepatectomy in mice. AB - BACKGROUND & AIMS: Hepatic stellate cells (HSCs) activate during injury to orchestrate the liver's inflammatory and fibrogenic responses. A critical feature of HSC activation is the rapid induction of beta platelet-derived growth factor (beta-PDGFR), which drives cellular fibrogenesis and proliferation; in contrast, normal liver has minimal beta-PDGFR expression. While the role of beta-PDGFR is well established in liver injury, its expression and contribution during liver regeneration are unknown. The aim of this study was to determine whether beta PDGFR is induced during liver regeneration following partial hepatectomy (pHx), and to define its contribution to the regenerative response. METHODS: Control mice or animals with HSC-specific beta-PDGFR-depletion underwent two-thirds pHx followed by assessment of hepatocyte proliferation and expression of beta-PDGFR. RNA-sequencing from whole liver tissue of both groups after pHx was used to uncover pathways regulated by beta-PDGFR signalling in HSCs. RESULTS: Beta platelet-derived growth factor expression on HSCs was up-regulated within 24 h following pHx in control mice, whereas absence of beta-PDGFR blunted the expansion of HSCs. Mice lacking beta-PDGFR displayed prolonged increases of transaminase levels within 72 h following pHx. Hepatocyte proliferation was impaired within the first 24 h based on Ki-67 and PCNA expression in beta-PDGFR deficient mice. This was associated with dysregulated growth in the beta-PDGFR deficient mice based on RNAseq with pathway analysis, and real-time quantitative PCR, which demonstrated reduced expression of Hgf, Igfbp1, Mapk and Il-6. CONCLUSIONS: Beta platelet-derived growth factor is induced in HSCs following surgical pHx and its deletion in HSCs leads to prolonged liver injury. However, there is no significant difference in liver regeneration. PMID- 26256288 TI - Extended follow-up of pediatric liver transplantation patients receiving once daily calcineurin inhibitor. AB - We describe longitudinal results in a cohort of pediatric liver transplant patients successfully minimized to once daily CNI monotherapy for longer than five yr and assess changes in liver biochemistries and liver histology. A retrospective chart review of all pediatric liver transplant patients at a single center was performed. Biopsies and serum biochemistries (AST, ALT, total bilirubin, direct bilirubin, INR, creatinine) are reported at time points: PM, five-yr, seven-yr, and nine-yr post-minimization. Biopsies were assessed for inflammation and fibrosis using Ishak and Batts grading systems. Successful minimization to daily CNI monotherapy was defined as normal liver enzymes with no episodes of rejection. Thirty-three patients have successfully remained on once daily CNI for >5 yr, and 19/33 of these patients have serial liver biopsies available for review. We report on the clinical and histological findings of these 19 patients. All 19 patients continue to have normal liver biochemistries. On post-minimization biopsies, fibrosis progressed by >=2 stages in one patient (5.3%) despite normal liver biochemistries. Carefully selected patients can tolerate minimization to once daily CNI monotherapy as few have progression of fibrosis. PMID- 26256289 TI - Preventing seasonal influenza worldwide through vaccination, education, and international cooperation: research, findings, and recommendations from the Global Influenza Initiative. PMID- 26256290 TI - Epidemiological and virological characteristics of influenza B: results of the Global Influenza B Study. AB - INTRODUCTION: Literature on influenza focuses on influenza A, despite influenza B having a large public health impact. The Global Influenza B Study aims to collect information on global epidemiology and burden of disease of influenza B since 2000. METHODS: Twenty-six countries in the Southern (n = 5) and Northern (n = 7) hemispheres and intertropical belt (n = 14) provided virological and epidemiological data. We calculated the proportion of influenza cases due to type B and Victoria and Yamagata lineages in each country and season; tested the correlation between proportion of influenza B and maximum weekly influenza-like illness (ILI) rate during the same season; determined the frequency of vaccine mismatches; and described the age distribution of cases by virus type. RESULTS: The database included 935 673 influenza cases (2000-2013). Overall median proportion of influenza B was 22.6%, with no statistically significant differences across seasons. During seasons where influenza B was dominant or co circulated (>20% of total detections), Victoria and Yamagata lineages predominated during 64% and 36% of seasons, respectively, and a vaccine mismatch was observed in ~25% of seasons. Proportion of influenza B was inversely correlated with maximum ILI rate in the same season in the Northern and (with borderline significance) Southern hemispheres. Patients infected with influenza B were usually younger (5-17 years) than patients infected with influenza A. CONCLUSION: Influenza B is a common disease with some epidemiological differences from influenza A. This should be considered when optimizing control/prevention strategies in different regions and reducing the global burden of disease due to influenza. PMID- 26256291 TI - Burden of influenza-associated deaths in the Americas, 2002-2008. AB - BACKGROUND: Influenza disease is a vaccine-preventable cause of morbidity and mortality. The Pan American Health Organization (PAHO) region has invested in influenza vaccines, but few estimates of influenza burden exist to justify these investments. We estimated influenza-associated deaths for 35 PAHO countries during 2002-2008. METHODS: Annually, PAHO countries report registered deaths. We used respiratory and circulatory (R&C) codes from seven countries with distinct influenza seasonality and high-quality mortality data to estimate influenza associated mortality rates by age group (0-64, 65-74, and >= 75 years) with a Serfling regression model or a negative binomial model. We calculated the percent of all R&C deaths attributable to influenza by age group in these countries (etiologic fraction) and applied it to the age-specific mortality in 13 countries with good mortality data but poorly defined seasonality. Lastly, we grouped the remaining 15 countries into WHO mortality strata and applied the age and mortality stratum-specific rate of influenza mortality calculated from the 20 countries. We summed each country's estimate to arrive at an average total annual number and rate of influenza deaths in the Americas. RESULTS: For the 35 PAHO countries, we estimated an annual mean influenza-associated mortality rate of 2.1/100,000 among <65-year olds, 31.9/100 000 among those 65-74 years, and 161.8/100,000 among those >= 75 years. We estimated that annually between 40,880 and 160,270 persons (mean, 85,100) die of influenza illness in the PAHO region. CONCLUSION: Influenza remains an important cause of mortality in the Americas. PMID- 26256292 TI - Should clinical case definitions of influenza in hospitalized older adults include fever? AB - INTRODUCTION: Influenza is a major cause of morbidity and mortality in elderly persons. Fever is included in all standard definitions of influenza-like illness (ILI), yet older patients may have diminished febrile response to infection. Therefore, we examined the utility of various thresholds to define fever for case definitions of influenza in persons >= 65 years of age. METHODS: Data from two prospective surveillance studies for respiratory viral infection in adults hospitalized with acute cardiopulmonary illnesses with or without fever were examined. The highest temperature reported prior to admission or measured during the first 24 h after admission was recorded. The diagnosis of influenza was made by a combination of viral culture, reverse-transcription polymerase chain reaction, antigen testing, and serology. RESULTS: A total of 2410 subjects (66% >= 65 years of age) were enrolled; 281 had influenza (261 influenza A, 19 influenza B, and one mixed influenza A and B). The commonly used definition of ILI (fever >= 37.8 degrees C and cough) resulted in 57% sensitivity and 71% specificity in older adults. Receiver operating characteristic curves examining the various temperature thresholds combined with cough and/or sore throat showed the optimal balance between sensitivity and specificity to be 37.9 degrees C (AUC 0.71) and 37.3 degrees C (AUC 0.66), in younger and older persons, respectively. CONCLUSION: Clinical decision rules using the presence of cough and fever may be helpful when screening for influenza or empiric antiviral treatment when rapid influenza testing is not available; however, lower fever thresholds may be considered for elderly subjects. PMID- 26256293 TI - The Global Influenza Initiative recommendations for the vaccination of pregnant women against seasonal influenza. AB - There is a heavy disease burden due to seasonal influenza in pregnant women, their fetuses, and their newborns. The main aim of this study was to review and analyze current evidence on safety, immunogenicity, and clinical benefits of the inactivated influenza vaccine (IIV) in pregnant women. Current evidence shows that in pregnant women, the seasonal and pandemic IIVs are safe and well tolerated. After vaccination, pregnant women have protective concentrations of anti-influenza antibodies, conferring immunogenicity in newborns. The best evidence, to date, suggests that influenza vaccination confers clinical benefits in both pregnant women and their newborns. Vaccination with either the seasonal or pandemic vaccine has been shown to be cost-effective in pregnancy. There are scarce data from randomized clinical trials; fortunately, new phase 3 clinical trials are under way. In the Northern and Southern Hemispheres, data suggest that the greatest clinical benefit for infants occurs if the IIV is administered within the first weeks of availability of the vaccine, at the beginning of the influenza season, regardless of the pregnancy trimester. The optimal timing to vaccinate pregnant women who live in tropical regions is unclear. Based on evaluation of the evidence, the Global Influenza Initiative (GII) recommends that to prevent seasonal influenza morbidity and mortality in infants and their mothers, all pregnant women, regardless of trimester, should be vaccinated with the IIV. For countries where vaccination against influenza is starting or expanding, the GII recommends that pregnant women have the highest priority. PMID- 26256294 TI - Retrospective public health impact of a quadrivalent influenza vaccine in the United States. AB - INTRODUCTION: Vaccination is an effective preventive strategy against influenza. However, current trivalent influenza vaccines (TIVs) contain only one of the two influenza B lineages that circulate each year. Vaccine mismatches are frequent because predicting which one will predominate is difficult. Recently licensed quadrivalent influenza vaccines (QIVs) containing the two B lineages should address this issue. Our study estimates their impact by assessing what would have been the US public health benefit of routinely vaccinating with QIV in 2000-2013. METHODS: We developed a dynamic compartmental model that accounts for interactions between influenza B lineages (natural or vaccine-induced) and simulates the multiyear influenza dynamics for 2000-2013. Age-structured population dynamics, vaccine efficacy (VE) per strain, and weekly ramp-up of vaccination coverage are modeled. Sensitivity analyses were performed on VE, duration of immunity, and levels of vaccine-induced cross-protection between B lineages. RESULTS: Assuming a cross-protection of 70% of the VE of the matched vaccine, the model predicts 16% more B lineage cases prevented by QIV. Elderly (>=65 years) and young seniors (50-64 years) benefit most from QIV, with 21% and 18% reductions in B lineage cases. Reducing cross-protection to 50%, 30%, and 0% of the VE of the matched vaccine improves the relative benefit of QIV to 25%, 30%, and 34% less B lineage cases. CONCLUSION: Using a dynamic retrospective framework with real-life vaccine mismatch, our analysis shows that QIV routine vaccination in the United States has the potential to substantially reduce the number of influenza infections, even with relatively high estimates of TIV induced cross-protection. PMID- 26256295 TI - A ruthenium(II) complex-based lysosome-targetable multisignal chemosensor for in vivo detection of hypochlorous acid. AB - Although considerable efforts have been made for the development of ruthenium(II) complex-based chemosensors and bioimaging reagents, the multisignal chemosensor using ruthenium(II) complexes as the reporter is scarce. In addition, the mechanisms of cellular uptake of ruthenium(II)-based chemosensors and their intracellular distribution are ill-defined. Herein, a new ruthenium(II) complex based multisignal chemosensor, Ru-Fc, is reported for the highly sensitive and selective detection of lysosomal hypochlorous acid (HOCl). Ru-Fc is weakly luminescent because the MLCT (metal-to-ligand charge transfer) state is corrupted by the efficient PET (photoinduced electron transfer) process from Fc (ferrocene) moiety to Ru(II) center. The cleavage of Fc moiety by a HOCl-induced specific reaction leads to elimination of PET, which re-establishes the MLCT state of the Ru(II) complex, accompanied by remarkable photoluminescence (PL) and electrochemiluminescence (ECL) enhancements. The result of MTT assay showed that the proposed chemosensor, Ru-Fc, was low cytotoxicity. The applicability of Ru-Fc for the quantitative detection of HOCl in live cells was demonstrated by the confocal microscopy imaging and flow cytometry analysis. Dye colocalization studies confirmed very precise distribution of the Ru(II) complex in lysosomes, and inhibition studies revealed that the caveolae-mediated endocytosis played an important role during the cellular internalization of Ru-Fc. By using Ru-Fc as a chemosensor, the imaging of the endogenous HOCl generated in live macrophage cells during the stimulation was achieved. Furthermore, the practical applicability of Ru-Fc was demonstrated by the visualizing of HOCl in laboratory model animals, Daphnia magna and zebrafish. PMID- 26256296 TI - Joint Manipulation Under Anesthesia for Arthrofibrosis After Hallux Valgus Surgery. AB - Arthrofibrosis is a known complication of hallux valgus surgery. Joint manipulation under anesthesia has been studied for adhesive capsulitis of the shoulder; however, a paucity of published data exists on the use of this modality in the foot and ankle. The purpose of the present study was to investigate the outcomes of first metatarsophalangeal joint manipulation for arthrofibrosis that occurred as a complication of bunion surgery. The study population consisted of patients attending a single foot and ankle specialty clinic who were evaluated for arthrofibrosis after bunion surgery. Patients who underwent joint manipulation under anesthesia were asked to complete a research visit in which a clinical examination was performed and the presence and severity of joint pain were assessed. A total of 38 patients (34 females, 4 males, 53 feet), with a mean age of 55.7 +/- 11.8 (range 30 to 83) years, agreed to participate. The mean follow-up period was 6.5 +/- 3.4 (range 1 to 17) years. The visual analog scale scores improved significantly from baseline to the final follow-up visit (baseline 6.5 +/- 1.5, range 2 to 10; final follow-up visit 2.3 +/- 1.5, range 0 to 6; p < .001). Furthermore, joint motion had increased significantly (p < .001) for both dorsiflexion and plantarflexion at the final follow-up examination. The final range of motion (dorsiflexion, r = -0.431, p = .002; plantarflexion, r = 0.494, p < .001) correlated highly with patient self-reported pain in the first metatarsophalangeal joint. Our findings suggest that joint manipulation could be a useful modality for increasing first metatarsophalangeal joint mobility and alleviating pain in patients who experience arthrofibrosis after surgical correction of hallux valgus. PMID- 26256297 TI - Influence of Hallux Rigidus on Reamputation in Patients With Diabetes Mellitus After Partial Hallux Amputation. AB - Diabetic foot ulceration of the plantar hallux is a challenging condition and can require partial hallux amputation when complicated by infection. Lower extremity biomechanics play an important role in the development of hallux ulcers, and hallux rigidus (HR) could influence the outcomes after partial hallux amputation. We hypothesized that radiographic evidence of HR in patients with diabetes would be associated with greater ulcer recurrence and reamputation rates after partial hallux amputation. We performed a retrospective review of all patients with diabetes who had undergone a partial hallux amputation from January 2005 to December 2012. The subjects were divided into 2 cohorts according to the presence or absence of HR identified on preoperative radiographs. Baseline characteristics and outcomes were compared using a 2-sample Student's t test for continuous variables, and categorical variables were compared using the chi-square test for homogeneity and Fisher's exact test. A total of 52 patients were included, with 16 (31%) positive for radiographic evidence of HR at partial hallux amputation. Differences in the patient demographics and comorbidities were not significant between 2 cohorts with and without HR or reamputation. Reamputation was required in 5 subjects (31%) with HR and 2 (6%) without HR (p = .023). The average follow up duration was 126 +/- 89 weeks. Our results have demonstrated that the reamputation rate after partial hallux amputation is significantly greater in patients with than in those without radiographic evidence of HR. Surgeons should evaluate patients for HR when planning partial hallux amputation and use adjuvant methods of offloading when HR is evident to prevent recurrent ulceration and reamputation. PMID- 26256298 TI - The Detection of Anti-adalimumab Antibodies in a Series of Inflammatory Polyarthritis: three ELISA Methods Compared. AB - BACKGROUND: A reliable identification of ADAb represents a fundamental tool in the followup of patients under treatment with anti-TNF drugs. OBJECTIVES: To compare three immunoenzymatic assays for anti-adalimumab antibodies (AAA) detection. METHODS: The study was performed in 40 patients with chronic inflammatory polyarthritis, comprising both patients showing a good response to adalimumab (ADL) and patients who lost response or did not respond to ADL, recently or in the past (retrospective study). Thus, sera were collected before ADL administration or well after ADL discontinuation. AAA were analysed by three different bridging ELISAs, following manufacturers' instructions. RESULTS: All methods disclosed negative results in responder patients and univocally recognized 11/31 (35.5%) AAA highpositive samples in non-responder patients, including several cases that had discontinued ADL for a long time (range 3-48 months). Among the overall non-responder patients, 10/31 (32.3%) disclosed concordant clear-cut AAA-negative results, while negative versus low-positive or borderline results were found in another ten non-responder patients, indicating slight differences in sensitivity between the methods, especially in patients who were analysed retrospectively. Methotrexate in combination therapy with ADL tended to be more frequent in AAA-negative, than in AAA-positive patients (52.6% vs. 25%; p=ns). CONCLUSIONS: The three bridging ELISA methods under study showed a good agreement and were able to identify uniquely the presence of high positive AAA, even after a long time since ADL discontinuation. PMID- 26256299 TI - Influence of metformin intake on the risk of bladder cancer in type 2 diabetes patients. AB - AIM: The aim of this study was to look at the influence of metformin intake and duration, on urinary bladder cancer (UBC) risk, with sulfonylurea (SU) only users as control using a new user design (inception cohort). METHODS: We conducted a retrospective cohort study using data from the UK Clinical Practice Research Datalink (CPRD) including all patients with at least one prescription of oral anti-diabetic drugs (ADD) and/or insulin. The risk of UBC in different groups of ADD users (metformin alone (one), metformin in combination (two) with other ADD medication (glinides, glitazones, DPP-4-inhibitors, SUs, insulin or more than one combination), all metformin users (1 + 2) was compared with SU only users using Cox proportional hazards models. The estimates were adjusted for age, gender, smoking status, BMI and diabetes duration. RESULTS: The inception cohort included 165,398 participants of whom 132,960 were metformin users and 32,438 were SU only users. During a mean follow-up time of more than 5 years 693 patients developed UBC, 124 of the control group and 461 of the all metformin users. There was no association between metformin use and UBC risk (HR = 1.12, 95% CI 0.90, 1.40) compared with SU only users, even after adjustment for diabetes duration (HR = 1.13, 95% CI 0.90, 1.40). We found a pattern of decreasing risk of UBC with increasing duration of metformin intake, which was statistically not significant. CONCLUSION: Metformin has no influence on the risk of UBC compared with SU in type 2 diabetes patients using a new user design. PMID- 26256300 TI - Propofol cardioplegia: A single-center, placebo-controlled, randomized controlled trial. AB - OBJECTIVES: Cardiac surgery with cardiopulmonary bypass and cardioplegic arrest is an effective treatment for coronary artery and aortic valve diseases. However, the myocardium sustains reperfusion injury after ischemic cardioplegic arrest. Our objective was to assess the benefits of supplementing cardioplegia solution with the general anesthetic propofol in patients undergoing either coronary artery bypass grafting (CABG) or aortic valve replacement (AVR). METHODS: A single-center, double-blind randomized controlled trial was carried out to compare cardioplegia solution supplemented with propofol (concentration 6 MUg/mL) versus intralipid (placebo). The primary outcome was cardiac troponin T release over the first 48 hours after surgery. RESULTS: We recruited 101 participants (51 in the propofol group, 50 in the intralipid group); 61 underwent CABG and 40 underwent AVR. All participants were followed to 3 months. Cardiac troponin T release was on average 15% lower with propofol supplementation (geometric mean ratio, 0.85; 95% confidence interval [CI], 0.73-1.01; P = .051). There were no differences for CABG participants but propofol-supplemented participants undergoing AVR had poorer postoperative renal function (geometric mean ratio, 1.071; 95% CI, 1.019-1.125; P = .007), with a trend toward longer intensive care stay (median, 89.5 vs 47.0 hours; hazard ratio, 0.58; 95% CI, 0.31-1.09; P = .09) and fewer with perfect health (based on the EQ-5D health utility index) at 3 months (odds ratio, 0.26; 95% CI, 0.06-1.05; P = .058) compared with the intralipid group. Safety profiles were similar. There were no deaths. CONCLUSIONS: Propofol supplementation in cardioplegia appears to be cardioprotective. Its influence on early clinical outcomes may differ between CABG and AVR surgery. A larger, multicenter study is needed to confirm or refute these suggestions. PMID- 26256302 TI - Nonexponential (1)H spin-lattice relaxation and methyl group rotation in molecular solids. AB - We report a quantitative measure of the nonexponential (1)H spin-lattice relaxation resulting from methyl group (CH3) rotation in six polycrystalline van der Waals solids. We briefly review the subject in general to put the report in context. We then summarize several significant issues to consider when reporting (1)H or (19)F spin-lattice relaxation measurements when the relaxation is resulting from the rotation of a CH3 or CF3 group in a molecular solid. PMID- 26256301 TI - Structure and Characterization of Eriphia verrucosa Hemocyanin. AB - Arthropod hemocyanins (Hcs) are a family of large extracellular oxygen transporting proteins with high molecular mass and hexameric or multi-hexameric molecular assembly. This study reports for the first time the isolation and characterization of the structure of an arthropod hemocyanin from crab Eriphia verrucosa (EvH) living in the Black Sea. Its oligomeric quaternary structure is based on different arrangements of a basic 6 * 75 kDa hexameric unit, and four of them (EvH1, EvH2, EvH3, and EvH4) were identified using ion-exchange chromatography. Subunit 3 (EvH3) shows high similarity scores (75.0, 87.5, 91.7, and 75.0 %, respectively) by comparison of the N-terminal sequence of subunit 1 from Cancer pagurus of the North Sea (Cp1), subunits 3 and 6 of Cancer magister (Cm3 and Cm6), and subunit 2 of Carcinus aestuarii (CaSS2), respectively. Moreover, a partial cDNA sequence (1309 bp) of E. verrucosa hemocyanin encoding a protein of 435 amino acids was isolated. The deduced amino acid sequence shows a high degree of similarity with subunits 3, 4, 5, and 6 of C. magister (81-84 %). Most of the hemocyanins are glycosylated, and three putative O-linkage sites were identified in the partial amino acid sequence of EvH at positions 444-446, 478 480, and 547-549, respectively. The higher stability of native Hc in comparison to its subunit EvH4 as determined by circular dichroism (CD) could be explained with the formation of a stabilizing quaternary structure. PMID- 26256303 TI - Enforcement of Zero Tolerance in the State of Washington - Evidence from Breath Test Records. AB - Several studies have demonstrated the effectiveness of zero tolerance (ZT) laws that make it illegal for drivers younger than 21 years to have any measurable alcohol in their bodies when operating a vehicle. All 50 states in the United States now have such laws. However, there is some question as to the extent they are being enforced. Because it has a centralized file of all breath tests performed by police in that state, Washington provided a special opportunity to evaluate the extent of ZT enforcement. Analyses were performed on arrests and alcohol-related fatal crashes of drivers younger than 21 years using data from the Washington State Patrol Breath Test Section and from the National Highway Traffic Safety Administration Fatality Analysis Reporting System, respectively. The results indicate that low blood alcohol concentration citations increased and crashes were reduced for drivers younger than 21 years, but crashes for drivers older than 21 years also declined. This suggests that the decline in underage drinking drivers in fatal crashes could not be unequivocally attributed to the ZT law. PMID- 26256304 TI - Handwriting Evidence in Federal Courts - From Frye to Kumho. AB - In federal courts, the admissibility of scientific expert testimony in the last century has been governed by three major standards. The first of these standards, the "general acceptance" test, arose from the 1923 Frye v. United States (Frye) and required that any technique or method introduced in court be generally accepted by the relevant community of scientists. The more liberal "relevancy" standard of the Federal Rules of Evidence was enacted in 1975, and required the expert witness to be qualified by knowledge, skill, experience, training, or education. Finally, the "reliability" standard stated in the Daubert v. Merrell Dow Pharmaceuticals, Inc. (Daubert) opinion was handed down by the U.S. Supreme Court in 1993, supplanting the Frye general acceptance test as the sole determining factor in considering the admissibility of scientific expert testimony, and suggesting falsifiability, peer review and publication, and error rate as additional factors useful in evaluating a scientific technique. Changing views on expert testimony have also resulted in published criticisms of several forensic fields, especially those with subjective components. The first such field to be questioned, which also has been the subject of great debate, is expert handwriting identification. Challenges leveled against handwriting identification began with a law review article published in 1989 (and two subsequent articles); other challenges have been based on the requirements outlined in the Federal Rules of Evidence and Daubert. These challenges resulted in several court opinions with disparate views of handwriting identification, though testimony by an expert in the field was not rejected. In U.S. v. Starzecpyzel, handwriting evidence was admitted as nonscientific expert testimony under the Federal Rules of Evidence after failing a review under the factors outlined in Daubert. In U.S. v. Velasquez (Velasquez), the testimony of a document examiner was accepted, while the testimony of an expert critic of handwriting identification was rejected by the district court; however, on appeal, the Third Circuit held that both witnesses met the requirements of the Federal Rules of Evidence, and thus both testimonies were admissible. U.S. v. Jones (Jones) demonstrated yet another situation, where handwriting identification was challenged under Daubert. There the court found that because handwriting identification was never viewed as scientific evidence under Frye, it should not therefore be reviewed under Daubert. The Jones court admitted handwriting identification as nonscientific evidence, but stated that admissibility of nonscientific evidence should be governed by the facts of future cases. After some time and many other opinions on the admissibility of expert testimony under Daubert, several federal circuits permitted review of nonscientific expert testimony under the factors outlined in Daubert, while other federal circuits restricted such reviews only to purportedly scientific testimonies. In the latter arenas, determining whether handwriting identification was a scientific field or not had bearing on how it was reviewed for admissibility, if it was reviewed at all. This situation ended in March 1999 with the U.S. Supreme Court opinion of Kumho Tire Co., Ltd. v. Carmichael (Kumho), which held that the Daubert factors may be used for review of all expert testimony as the courts see fit, regardless of whether the field is considered scientific. In the wake of Kumho, two other cases challenged handwriting identification: U.S. v. Paul (Paul) and U.S. v. Hines (Hines). The Paul case, like Velasquez, dealt with exclusion of an expert critic of handwriting identification, and also like Velasquez, the court appeared to rely on the Federal Rules of Evidence rather than the factors outlined in Daubert to form its judgment. Hines, however, represented a significant departure from earlier cases, as handwriting identification was partially excluded in that the document examiner was permitted to testify to similarities and differences but was not allowed to opine as to the authorship. In sum, the federal courts are currently evaluating the admissibility of handwriting identification in a variety of ways. Though handwriting identification continues to be widely admitted as a form of expert testimony, the recent changes in admissibility requirements and challenges from the legal community have generated a climate where admissibility should no longer to be taken for granted. Because Kumho is a relatively recent case, its long-term effects on the admissibility of many fields of forensic science, including handwriting identification, are yet unknown. PMID- 26256305 TI - Postmortem Drug Redistribution. AB - One of the most difficult responsibilities of the forensic toxicologist is the interpretation of postmortem drug levels and their possible significance as to behavior and/or cause of death. During the past 15 years, much work has been performed using human case information and animal studies to illustrate and validate the phenomena of postmortem drug redistribution. These studies provide certain clarification to drug level interpretation. They also cast uncertainty on the interpretation of drugs where analogous studies are incomplete or totally absent. Literature data of more than 30 drugs, as reported by numerous authors, are reviewed to illustrate two phenomena: (a) postmortem redistribution occurs primarily as a function of the diffusion of drugs along a concentration gradient, from sites of high concentration in solid organs into the blood with artificial elevation of the drug levels; and (b) while many drugs seem to subject to postmortem redistribution, there are also others that undergo no change whatsoever. While additional work still needs to be performed, there has been enough achieved to both illustrate and validate that postmortem redistribution does exist. This information is helpful to forensic pathologists in determining sample sets taken during autopsy. PMID- 26256306 TI - Somatic and Germline Mutation of Forensic DNA Markers. AB - Somatic and germline mutations of forensic DNA markers DQA1, PM, STR, minisatellite DNA, and mtDNA are reviewed in this paper. DQA1 and PM are stable point substitution polymorphic loci in nuclear DNA (nucDNA); thus, somatic and germline mutations are rarely reported. STR loci somatic mutations are not found in normal cells but are very unstable in cancer cells. Germline mutations are detected in STR loci with a mutation rate of approximately 0.1%. Germline mutations of STR loci are nucleotide sequence, sex, and age dependent. Among the 13 CODIS core, TH01, TPOX, D16S539, and D3S1358 are more stable than others. Both somatic and germline mutations are found in minisatellite loci. Somatic mutations at mtDNA central region (CR) are detected in different tissues within the same individual, and the mutation rates are high in several cancer tissues. The intergenerational mutation rate of mtDNA CR is estimated to be 1/400 to 1/1200 per generation by phylogenetic analysis. The intergenerational mutation rate estimated by the recently developed pedigree method is higher, 14/1221 (1/87). This rate does not include the hot spot and heteroplasmic mutation. If substitution, heteroplasmic, and poly-C tract mutation are included, the mutation rate of mtDNA CR is 33/1590 (1/49) per generation. Proposals and practices on the interpretation of test data that may be associated with mutation are also discussed. PMID- 26256307 TI - Surgical Treatment for Traumatic Brain Injury: Is It Time for Reappraisal? PMID- 26256308 TI - Heavy metal pollution in the surface water of the Yangtze Estuary: A 5-year follow-up study. AB - The temporal-spatial changes in the concentration and health risk of eight dissolved heavy metals in the Yangtze Estuary over a 5-year period were discussed based on large-scale sampling data. Special attention was paid to the differentiation of metal sources. Concentrations of the metals were present in the following order: Zn?As>Cu>Cr>Ni>Pb>Cd>Hg, but the hazard quotient indices could be obviously divided into three gradients. More attention should be paid to As, Ni, Pb, and Cr because they increased yearly. Cu, Ni, Pb and As had higher health risks in the nearshore zones, while higher health risks of Zn, Cr, Cd, and Hg were observed in the estuarine channel. Correlations and hierarchical cluster analysis results of metal sources were consistent well with those obtained by temporal-spatial distributions. Shipping activities were the largest contributor to the elevated Zn concentrations in the estuary, while Megacity Shanghai significantly affected the Ni, Cu and As pollution. Yangtze River runoff was the primary source of Cu and As in the estuary. Cd and Cr pollution were closely related to the sediment release under the drive of the "salt-out effect". PMID- 26256309 TI - Copper and zinc accumulation and fractionation in a clayey Hapludox soil subject to long-term pig slurry application. AB - Pig slurry (PS) recycling as fertilizer is commonly practiced as an option for minimizing livestock waste. Successive PS applications on the soil can lead to crop toxicity and environmental risk. Despite extensive investigation of macronutrient behavior, the fate of trace metals remains uncertain and only a few long-term field studies have been reported to date. This study was designed to assess the impact of 11-year continuous PS spreading on Cu and Zn accumulation and fractionation in a Brazilian clayey Hapludox soil. Three different PS application rates--50, 100 and 200m3 ha(-1)year(-1)--were monitored at six soil depths in comparison to a non-amended control soil. The modified Geological Survey of Canada sequential extraction protocol was applied. A statistically significant increase in Cu and Zn total concentration (assessed by the sum of fractions) was noted only within the 0-5 cm soil layer for the 50 and 100 m3 ha( 1) year(-1) (PS50 and PS100) treatments, and up to 10-15 cm for the 200 m3 ha( 1)year(-1) (PS200) treatment. The mass balance, determined for the 22 PS amendments over the period, confirmed the overall exogenous Cu and Zn accumulation within the surface layers. More than 70% of the natural heavy metal content was originally in the residual fraction. However, this was the only fraction not influenced by the PS amendments. After PS input, the exogenous Cu was mainly detected in the fraction bound to organic matter (66.4%) within the PS200 0-5 cm soil layer. Exogenous Zn was mainly distributed between the adsorbed fraction (36.7%) and the organic matter fraction (32.0%) within the PS200 0-5 cm layer. PMID- 26256310 TI - Orthogonal Ternary Functionalization of a Mesoporous Metal-Organic Framework via Sequential Postsynthetic Ligand Exchange. AB - A sequential postsynthetic ligand exchange process was used to prepare a series of mono-, di-, and trifunctionalized mesoporous metal-organic frameworks (MOFs). Using this process, orthogonal functional groups were installed and thereafter postsynthetically modified with dye and quencher molecules. Microspectrophotometry studies were used to determine the distribution of the two orthogonal functional groups within the MOF crystals. PMID- 26256311 TI - Assembling the dodo in early modern natural history. AB - This paper explores the assimilation of the flightless dodo into early modern natural history. The dodo was first described by Dutch sailors landing on Mauritius in 1598, and became extinct in the 1680s or 1690s. Despite this brief period of encounter, the bird was a popular subject in natural-history works and a range of other genres. The dodo will be used here as a counterexample to the historical narratives of taxonomic crisis and abrupt shifts in natural history caused by exotic creatures coming to Europe. Though this bird had a bizarre form, early modern naturalists integrated the dodo and other flightless birds through several levels of conceptual categorization, including the geographical, morphological and symbolic. Naturalists such as Charles L'Ecluse produced a set of typical descriptive tropes that helped make up the European dodo. These long lived images were used for a variety of symbolic purposes, demonstrated by the depiction of the Dutch East India enterprise in Willem Piso's 1658 publication. The case of the dodo shows that, far from there being a dramatic shift away from emblematics in the seventeenth century, the implicit symbolic roles attributed to exotic beasts by naturalists constructing them from scant information and specimens remained integral to natural history. PMID- 26256312 TI - Making Kew Observatory: the Royal Society, the British Association and the politics of early Victorian science. AB - Built in 1769 as a private observatory for King George III, Kew Observatory was taken over in 1842 by the British Association for the Advancement of Science (BAAS). It was then quickly transformed into what some claimed to be a 'physical observatory' of the sort proposed by John Herschel - an observatory that gathered data in a wide range of physical sciences, including geomagnetism and meteorology, rather than just astronomy. Yet this article argues that the institution which emerged in the 1840s was different in many ways from that envisaged by Herschel. It uses a chronological framework to show how, at every stage, the geophysicist and Royal Artillery officer Edward Sabine manipulated the project towards his own agenda: an independent observatory through which he could control the geomagnetic and meteorological research, including the ongoing 'Magnetic Crusade'. The political machinations surrounding Kew Observatory, within the Royal Society and the BAAS, may help to illuminate the complex politics of science in early Victorian Britain, particularly the role of 'scientific servicemen' such as Sabine. Both the diversity of activities at Kew and the complexity of the observatory's origins make its study important in the context of the growing field of the 'observatory sciences'. PMID- 26256313 TI - Finding revelation in anthropology: Alexander Winchell, William Robertson Smith and the heretical imperative. AB - Anthropological inquiry has often been considered an agent of intellectual secularization. Not least is this so in the sphere of religion, where anthropological accounts have often been taken to represent the triumph of naturalism. This metanarrative, however, fails to recognize that naturalistic explanations could sometimes be espoused for religious purposes and in defence of confessional creeds. This essay examines two late nineteenth-century figures- Alexander Winchell in the United States and William Robertson Smith in Britain- who found in anthropological analysis resources to bolster rather than undermine faith. In both cases these individuals found themselves on the receiving end of ecclesiastical censure and were dismissed from their positions at church-governed institutions. But their motivation was to vindicate divine revelation, in Winchell's case from the physical anthropology of human origins and in Smith's from the cultural anthropology of Semitic ritual. PMID- 26256314 TI - Sounding the field: recent works in sound studies. AB - For sound studies, the publication of a 593-page handbook, not to mention the establishment of at least one society - the European Sound Studies Association - might seem to signify the emergence of a new academic discipline. Certainly, the books under consideration here, alongside many others, testify to an intensification of concern with the aural dimensions of culture. Some of this work comes from HPS and STS, some from musicology and cultural studies. But all of it should concern members of our disciplines, as it represents a long-overdue foregrounding of the aural in how we think about the intersections of science, technology and culture. PMID- 26256315 TI - A survey of medicinal plants for diabetes treating from Chana and Nathawee district, Songkhla province, Thailand. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Diabetes mellitus is a chronic disease which cannot be cured and must be suffered for whole life. Nowadays, many patients wanting to treat themselves by herbal medicine are increasing. Therefore, surveying of medicinal plants for treating diabetes and disseminating the knowledge, might give people more choice to consume herbs. The purposes of this qualitative study were to compile the medicinal plants and their folk use to treat diabetes by local healers in Chana and Nathawee district, Songkhla province. MATERIALS AND METHODS: Semi-structured interviews were used to gather about the local names, parts of plants used, preparation and use method, and local properties. Descriptive statistics, use value and interpretation were used to analyze the data. RESULTS: A total of 38 species belonging to 37 genera in 28 families were used as herbs for treating diabetes. The family mostly used as herbal medicine was Rubiaceae (4 species; 10.53%). The part of herbal medicine mostly used was the root (8 speciess; 21.05%). Decoction and drinking were the most favorite preparation form and use method. Interestingly, the most used herbal plant is Lagerstraemia speciose Pers (0.83 of Use Value). CONCLUSION: It was found that the local healers possess the different knowledge based on their experience received secretly from the family and adapted by themselves. Thus, this study is important due to assistance for collecting the variety of knowledge before disappearing. PMID- 26256316 TI - Antinociceptive properties of the aqueous and methanol extracts of the stem bark of Petersianthus macrocarpus (P. Beauv.) Liben (Lecythidaceae) in mice. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Aqueous maceration from the stem barks of Petersianthus macrocarpus (P. Beauv.) Liben (Lecythidaceae) is taken orally in the central Africa for the management of various ailments, including pain. AIM OF THE STUDY: This work was carried out to evaluate in mice, the antinociceptive effects of the aqueous and methanol extracts of the stem bark of P. macrocarpus. MATERIALS AND METHODS: The chemical composition of the aqueous and methanol extracts prepared as cold macerations was determined by high performance liquid chromatography coupled with mass spectrometry (LCMS). The antinociceptive effects of these extracts administered orally at the doses of 100, 200 and 400 mg/kg were evaluated using behavioral pain model induced by acetic acid, formalin, hot plate, capsaicin and glutamate. The rotarod test was also performed at the same doses. The oral acute toxicity of both extracts was studied at the doses of 800, 1600, 3200 and 6400 mg/kg in mice. RESULT: The LCMS analysis revealed the presence of ellagic acid as the major constituent in the methanol extract. Both extracts of P. macrocarpus significantly and dose dependently reduced the time and number of writhing induced by acetic acid. They also significantly inhibited the two phases of formalin-induced pain. These effects were significantly inhibited by a pretreatment with naloxone, except for the analgesic activity of the methanol extract at the earlier phase. In addition, nociception induced by hot plate, intraplantar injection of capsaicin or glutamate was significantly inhibited by both extracts. Acute toxicity test showed no sign of toxicity. CONCLUSION: These results demonstrate that aqueous and methanol extracts of P. macrocarpus are none toxic substances with good central and peripheral antinociceptive effects that are at least partially due to the presence of ellagic acid. These extracts may induce their antinociceptive effect by interfering with opioid, capsaicin and excitatory amino acid pathways. PMID- 26256317 TI - Biodegradability and mechanical properties of reinforced starch nanocomposites using cellulose nanofibers. AB - In this study the effects of chemical modification of cellulose nanofibers (CNFs) on the biodegradability and mechanical properties of reinforced thermoplastic starch (TPS) nanocomposites was evaluated. The CNFs were modified using acetic anhydride and the nanocomposites were fabricated by solution casting from corn starch with glycerol/water as the plasticizer and 10 wt% of either CNFs or acetylated CNFs (ACNFs). The morphology, water absorption (WA), water vapor permeability rate (WVP), tensile, dynamic mechanical analysis (DMA), and fungal degradation properties of the obtained nanocomposites were investigated. The results demonstrated that the addition of CNFs and ACNFs significantly enhanced the mechanical properties of the nanocomposites and reduced the WVP and WA of the TPS. The effects were more pronounced for the CNFs than the ACNFs. The DMA showed that the storage modulus was improved, especially for the CNFs/TPS nanocomposite. Compared with the neat TPS, the addition of nanofibers improved the degradation rate of the nanocomposite and particularly ACNFs reduced degradation rate of the nanocomposite toward fungal degradation. PMID- 26256318 TI - Fluctuation in physicochemical properties of chitins extracted from different body parts of honeybee. AB - It is well known that physicochemical properties of chitin are related with the extraction method. Recently, it was revealed that some physicochemical properties of chitin are also related with taxonomical relationship. For the first time in this study, it was tested how these properties of chitin are affected by different body parts of one organism. The chitins were extracted from five different body parts (head, thorax, abdomen, legs and wings) of honeybee. These chitins were physicochemically characterized and differences among these body parts were identified. Highest chitin content was observed in legs (13.25%) while the lowest from thorax (6.79%). The surface morphologies of the isolated chitin structures from five different body parts were analyzed with SEM, as a result, five different types of surface morphologies were recorded. However, three different types of surface morphologies were observed only in abdomen. Maximum degradation temperatures (DTG(max)) of thorax, abdomen, legs and wings were recorded between 359 and 367 degrees C while DTG(max) value of head chitin was found as 308 degrees C. PMID- 26256319 TI - Effect of the degree of substitution of octenyl succinic anhydride-banana starch on emulsion stability. AB - Banana starch was esterified with octenylsuccinic anhydride (OSA) at different degree substitution (DS) and used to stabilize emulsions. Morphology, emulsion stability, emulsification index, rheological properties and particle size distribution of the emulsions were tested. Emulsions dyed with Solvent Red 26 showed affinity for the oil phase. Backscattering light showed three regions in the emulsion where the emulsified region was present. Starch concentration had higher effect in the emulsification index (EI) than the DS used in the study because similar values were found with OSA-banana and native starches. However, OSA-banana presented greater stability of the emulsified region. Rheological tests in emulsions with OSA-banana showed G'>G" values and low dependence of G' with the frequency, indicating a dominant elastic response to shear. When emulsions were prepared under high-pressure conditions, the emulsions with OSA banana starch with different DS showed a bimodal distribution of particle size. The emulsion with OSA-banana starch and the low DS showed similar mean droplet diameter than its native counterpart. In contrast, the highest DS led to the highest mean droplet diameter. It is concluded that OSA-banana starch with DS can be used to stabilize specific emulsion types. PMID- 26256320 TI - NaOH treatment of chitosan films: Impact on macromolecular structure and film properties. AB - In this paper, we examine the significance of treatment with NaOH on chitosan (CH) film structure to obtain biodegradable materials for several applications. In order to determine the structure of the films, an analysis based on SEM, FTIR spectroscopy and X-ray diffraction data was performed. In addition, the consequences of this treatment were evaluated by swelling index measurements and mechanical testing. As result of FTIR and X-ray analysis, three effects were identified: the deprotonation and phosphate extraction, which allowed new hydrogen bonds to form, and a higher CH deacetylation. These studies also revealed that two hydrated and anhydrous polymorphs were present in the CH-NaOH films. Moreover, the new hydrogen bond and the reduction of N-acetyl groups produced films with a more compact and disordered structure, reducing their swelling characteristics and increasing their brittleness. The introduction of a mild NaOH treatment is a versatile tool to obtain chitosan films with interesting and tunable properties. PMID- 26256321 TI - Characterization, antioxidant and antitumor activities of polysaccharides from purple sweet potato. AB - Three polysaccharides, PSPP1-1, PSPP2-1 and PSPP3-1, were isolated from purple sweet potato. The three polysaccharides belonged to beta-type polysaccharides and contained low proportions of proteins and uronic acids. PSPP1-1 and PSPP3-1 with molecular weights of 33.3 and 75.3 kDa, respectively, were composed of rhamnose, xylose, glucose and galactose, whereas PSPP2-1 with molecular weight of 17.8 kDa was composed of rhamnose and galactose. The three polysaccharides possessed in vitro antioxidant (scavenging DPPH radicals, chelating ferrous ions and reducing power) and antitumor activities (against SGC7901 and SW620 cells) in a dose dependent manner. Among the three polysaccharides, PSPP2-1 exhibited the strongest reducing power, scavenging activity on DPPH radicals and chelating capability on ferrous ions. PSPP1-1 showed the strongest inhibitory activities on the growth of SGC7901 and SW620 cells. In addition, flow cytometry results showed that PSPP1-1 could induce apoptosis in SGC7901 and SW620 cells. These results suggest that polysaccharides from purple sweet potato are potential natural antioxidant and antitumor agents that can be used as drugs or functional food ingredients. PMID- 26256322 TI - Enzymatic synthesis of 2-deoxyglucose-containing maltooligosaccharides for tracing the location of glucose absorption from starch digestion. AB - The ileal brake mechanism which induces a potentially beneficial slower gastric emptying rate and increased satiety is triggered by macronutrients including glucose from glycemic carbohydrates. For optimization of this diet-induced health benefit, there is the need for a way to determine the location of glucose deposition in the small intestine. Labeled 2-deoxyglucose (2-DG) can be used to trace the location of glucose absorption due to its accumulative property in the small intestine enterocytes. However, because pure glucose, or 2-DG, is directly absorbed in the proximal small intestine, we designed 2-DG containing maltooligosaccharides (2-DG-MOs) that can be used with a mild alpha-glucosidase inhibitor to attain an analytical method for determining location-specific delivery of glucose and its physiological effect. PMID- 26256323 TI - Macroporous chitosan hydrogels: Effects of sulfur on the loading and release behaviour of amino acid-based compounds. AB - Chitosan is a biodegradable, biocompatible polymer of natural origin widely applied to the preparation of functional hydrogels suitable for controlled release of drugs, peptides and proteins. Non-covalent interactions, expecially ionic interactions, are the main driver of the loading and release behaviour of amino acids or peptides from chitosan hydrogels. With the aim to improve the understanding of the mechanisms governing the behaviour of chitosan hydrogels on peptide uptake and delivery, in this paper the attention was focused on the role played by sulfur on the interactions of chitosan hydrogels with sulfur-containing amino acids (AA) and peptides. Hence, loading and release experiments on cysteine, cystine and glutathione (SH containing amino acid, dipeptide and tripeptide, respectively) as well as on glycine and valine as apolar amino acids were carried out. For these puroses, chitosan hydrogels were prepared in an easy and reproducible manner by a freeze-gelation process on a poly-L-lysine coated support. The hydrogel surface pore size, uniformity and distribution were tested. Optimal results (D50 = 26 +/- 4 MUm) were obtained by using the poly-L-lysine positively-charged surface. The loading results gathered evidenced that the sulfur-containing molecules presented an increased absorption both in terms of rate and extent by chitosan hydrogels with respect to nonpolar amino acids, mainly due to ionic and hydrogen bond interactions. ATR-FTIR analysis carried out on chitosan hydrogels, with and without the AA related compounds to study putative interactions, supported these apparent sulfur-dependent results. Finally, chitosan hydrogels displayed excellent retention capabilities (AA release <5%) for all AA, strongly supporting the use of chitosan hydrogels as matrix for controlled drug release. PMID- 26256324 TI - Characterisation of branched gluco-oligosaccharides to study the mode-of-action of a glucoamylase from Hypocrea jecorina. AB - In the conversion of starch to fermentable glucose for bioethanol production, hydrolysis of amylopectin by alpha-amylases and glucoamylases is the slowest step. In this process, alpha-1,6-branched gluco-oligosaccharides accumulate and are slowly degraded. Glucoamylases that are able to degrade such branched oligosaccharides faster are economically beneficial. This research aimed at the isolation and characterisation of branched gluco-oligosaccharides produced from amylopectin digestion by alpha-amylase, to be used as substrates for comparing their degradation by glucoamylases. Branched gluco-oligosaccharides with a DP between five and twelve were purified using size exclusion chromatography. These structures were characterised after labelling with 2-aminobenzamide using UHPLC MS(n) analysis. Further, the purified oligosaccharides were used to evaluate the mode-of-action of a glucoamylase from Hypocrea jecorina. The enzyme cleaves the alpha-1,4-linkage adjacent to the alpha-1,6-linkage at a lower rate than that of alpha-1,4-linkages in linear oligosaccharides. Hence, the branched gluco oligosaccharides are a suitable substrate to evaluate glucoamylase activity on branched structures. PMID- 26256325 TI - Purification, structural characterization and anticancer activity of the novel polysaccharides from Rhynchosia minima root. AB - Three novel acidic polysaccharides termed PRM1, PRM3 and PRM5 were purified from Rhynchosia minima root using DEAE-52 cellulose and sephadex G-150 column chromatography. Their structures were characterized by ultraviolet (UV) and Fourier transform infrared (FTIR) spectrometry, gel permeation chromatography (GPC), gas chromatography-mass spectrometry (GC-MS), and differential scanning colorimeter (DSC) analysis. The uronic acid contents of PRM1, PRM3 and PRM5 were 30.7%, 12.7% and 47.7%, respectively. PRM1 (143.2 kDa), PRM3 (105.3 kDa) and PRM5 (162.1 kDa) were heteropolysaccharides because they were composed of arabinose, mannose, glucose and galactose. Their enthalpy values were 201.0, 111.0 and 206.8 J/g, respectively. PRM3 and PRM1 exhibited strong in vitro anticancer activity against lung cancer A549 and liver cancer HepG2 cells in a dose-dependent manner. These findings suggested that PRM1 and PRM3 could be potentially developed as natural anticancer agents. PMID- 26256326 TI - Acinetobacter haemolyticus MG606 produces a novel, phosphate binding exobiopolymer. AB - The present study evaluated an extracellular, novel biopolymer produced by Acinetobacter haemolyticus MG606 for its physicochemical properties and phosphate binding mechanism. The exobiopolymer (EBP) was characterized to be majorly polysaccharide in nature consisting of 48.9 kDa heteropolysaccharide composed of galactose, glucose, xylose, lyxose, allose, ribose, arabinose, mannose and fructose. Maximum phosphate binding efficiency of 25mg phosphate/g of EBP was described by Langmuir isotherm and further, the physicochemical and spectroscopic studies revealed that phosphate appeared to bind predominantly with the polysaccharide fraction, and to a relatively lesser extent to protein fraction of EBP. The electrostatic interactions with amino groups and ligand exchange with hydroxyl groups of EBP were found to be primary basis for phosphate binding mechanism. The results of this study implicate the feasibility of the EBP for commercial bioremediation processes. PMID- 26256327 TI - Cyclodextrin/dextran based hydrogels prepared by cross-linking with sodium trimetaphosphate. AB - Novel betaCD-based hydrogels have been synthesized using sodium trimetaphosphate (STMP) as non-toxic reagent. Straightforward mixing of betaCD with dextran and STMP in basic aqueous media led to hydrogels incorporating dextran chains, phosphate groups and betaCD units. The hydrogels have been characterized by swelling measurements, XPS and (31)P NMR. The swelling ratio was correlated to the content in phosphated groups, which give a polyelectrolyte character to these hydrogels. The significant rise of the swelling ratio with the betaCD content increase has been attributed to a decrease of the number of phosphate-based crosslinks, the betaCD units playing the role of dangling ends in the tridimensional network. Their loading capacity and their release properties have been investigated for methylene blue and benzophenone in order to demonstrate their potentiality for drug delivery. Through different interaction mechanisms, electrostatic and inclusion complex interactions, these compounds are loaded with different efficiencies. The release involves deswelling, diffusion mechanisms and partition equilibrium. PMID- 26256328 TI - Elimination of reactive blue 4 from aqueous solutions using 3-aminopropyl triethoxysilane modified chitosan beads. AB - The adsorption behavior of chitosan (CS) beads modified with 3-aminopropyl triethoxysilane (APTES) for the removal of reactive blue 4 (RB4) in batch studies has been investigated. The effects of modification conditions, such as the APTES concentration, temperature and reaction time on RB4 removal, were studied. The adsorbent prepared at a concentration of 2 wt% APTES for 8h at 50 degrees C was the most effective one for RB4 adsorption. The adsorption capacity of modified CS beads (433.77 mg/g) was 1.37 times higher than that of unmodified CS beads (317.23 mg/g). The isotherm data are adequately described by a Freundlich model, and the kinetic study revealed that the pseudo-second-order rate model was in better agreement with the experimental data. The negative values of the thermodynamic parameters, including DeltaG degrees (-2.28 and -4.70 kJ/mol at 30 +/- 2 degrees C), DeltaH degrees (-172.18 and -43.82 kJ/mol) and DeltaS degrees (-560.71 and -129.08 J/mol K) for CS beads and APTES modified beads, respectively, suggest that RB4 adsorption is a spontaneous and exothermic process. PMID- 26256329 TI - Modification of potato peel waste with base hydrolysis and subsequent cationization. AB - Potato peel waste (PW) is a starch containing biomaterial produced in large amounts by food processing industry. In this work, the treatment of PW by alkaline hydrolysis and cationization in the water phase is reported. In order to improve the cationization of starch, PW was hydrolyzed by heating with alkaline (NaOH) ethanol solution (80%) in a water bath. The impact of variable molar ratios of anhydroglucose unit (AGU):NaOH, heating temperatures and times was studied on the degradation of starch and the molecular size distribution of the product. The hydrolyzed PW was cationized subsequently in water by using glycidyltrimethylammonium chloride and catalyzed by NaOH under microwave irradiation or in an oil bath. The impact of the various reaction conditions on the cationization and degree of substitution of starch was studied. The degree of substitution of the cationized starch varied in the range of 0-0.35. PMID- 26256330 TI - Synthesis of fibrinolytic active silver nanoparticle using wheat bran xylan as a reducing and stabilizing agent. AB - A facile synthesis of highly stable silver nanoparticles (AgNPs) was reported using a biopolymer, xylan as both a reducing and stabilizing agent. Xylan was isolated from waste biomass, wheat bran (WB) by alkaline treatment and was characterized by Fehling's test, dinitrosalicylic acid assay, FTIR, (1)H NMR and (13)C NMR. The synthesized nanoparticles were characterized by UV-Vis spectroscopy and transmission electron microscopy. The nanoparticles were polydispersed with the size ranging from 20 to 45 nm. The synthesized WB-xylan AgNPs showed excellent free radical scavenging activity. In addition, WB-xylan AgNPs showed fibrinolytic activity as evidenced by the zone of clearance in fibrin plate assay. The biomedical potential of the WB-xylan AgNPs was demonstrated by dissolution of preformed blood clots. These results suggest that the development of xylan-metal nanoparticle composite would be feasible to treat thrombus related diseases. PMID- 26256331 TI - Preharvest treatments with chitosan and other alternatives to conventional fungicides to control postharvest decay of strawberry. AB - The effectiveness of the control of postharvest decay of strawberry (Fragaria * ananassa, 'Alba' and 'Romina' cvs.) fruit following field applications of chitosan, laminarin, extracts of Abies spp., Polygonum spp., and Saccharomyces spp., an organic acids and calcium combination, and benzothiadiazole, were compared with a fungicide strategy. These compounds were sprayed every 5 days on the strawberry canopy, from flowering to ripening, in 2012 and 2013. The treatments with alternative compounds provided ~ 30% reduction in postharvest decay of strawberry compared to the water-treated controls, mainly against gray mold and Rhizopus rot, and without negatively affecting fruit color and firmness. Chitosan and benzothiadiazole were the most effective alternative treatments. Preharvest spraying with these alternative treatments can complement the use of conventional fungicides in the control of postharvest decay of strawberry fruit, especially when disease pressure is low. PMID- 26256332 TI - Structure and anticancer activity in vitro of sulfated galactofucan from brown alga Alaria angusta. AB - Laminaran and three fractions of fucoidan were isolated from brown alga Alaria angusta. The laminaran AaL was characterized as a typical 1,3;1,6-beta-D-glucan (ratio of bonds 1,3:1,6 = 10:1). Fucoidans AaF1 and AaF2 are sulfated heteropolysaccharides, containing fucose, galactose, mannose and xylose. The fraction AaF3 is sulfated and acetylated galactofucan with the main chain represented by a repeating unit -> 3)-alpha-L-Fucp-(2,4-SO3(-))-(1 ->. According the data of methylation analysis, AaF3 contains mainly 1,3-linked fucose, less 1,4-linked and 1,4,6-linked galactose residues. The autohydrolysis (37 degrees C) of fucoidan AaF3 allowed to obtain selectively 2-desulfaled polysaccharide fraction, built up of fucose only, and low molecular weight (LMW) fraction. The negative-ion tandem mass spectrometry of LMW fraction, further hydrolyzed by acid hydrolysis identified the following fragments: Gal-2-SO3(-)-(1 -> 4)-Gal, Gal-4 SO3(-)-(1 -> 4)-Gal, Gal-(1 -> 2)-Gal-4-SO3(-), Fuc-2-SO3(-)-(1 -> 4)-Gal, Gal-2 SO3(-)-(1 -> 3)-Fuc-(1 -> 3)-Fuc, Fuc-2-SO3(-)-(1 -> 3)-Fuc-(1 -> 4)-Gal. The laminaran AaL and the fucoidan AaF3 exhibited no cytotoxicity in vitro for HT 29, T-47D, and SK-MEL-28 cell lines. The AaF3 fraction suppressed colony formation of HT 29 and T-47D cells, AaL-only HT 29 cells. PMID- 26256333 TI - In situ synthesis of nano ZnO on starch sized cotton introducing nano photo active fabric optimized with response surface methodology. AB - In this study the idea of in situ synthesis of ZnO nanoparticles on starch sized raw cotton fabric was followed to produce white cotton fabric with durable self cleaning activity and tunable wettability. Alkaline condition of the preparation procedure played a prominent role in the synthesis and adsorption of ZnO nanoparticles on the cellulosic fabric. Moreover, starch size assisted the synthesis procedure and controlling the size of nanoparticles. The successful synthesis of nano ZnO particles on the treated fabrics was confirmed with XRD, FESEM and EDX. A central composite design based on response surface methodology was applied to study the influence of zinc nitrate and NaOH concentration, and their appropriate percentage for the best photoactivity and whiteness was obtained. The treated fabrics indicated good self-cleaning property toward degradation of Methylene Blue stain under sunlight irradiation while simultaneously benefited from higher whiteness due to the photo activity of nano white ZnO that is called "nano-photo bleaching". PMID- 26256334 TI - The nanostructural characterization of strawberry pectins in pectate lyase or polygalacturonase silenced fruits elucidates their role in softening. AB - To ascertain the role of pectin disassembly in fruit softening, chelated- (CSP) and sodium carbonate-soluble (SSP) pectins from plants with a pectate lyase, FaplC, or a polygalacturonase, FaPG1, downregulated by antisense transformation were characterized at the nanostructural level. Fruits from transgenic plants were firmer than the control, although FaPG1 suppression had a greater effect on firmness. Size exclusion chromatography showed that the average molecular masses of both transgenic pectins were higher than that of the control. Atomic force microscopy analysis of pectins confirmed the higher degree of polymerization as result of pectinase silencing. The mean length values for CSP chains increased from 84 nm in the control to 95.5 and 101 nm, in antisense FaplC and antisense FaPG1 samples, respectively. Similarly, SSP polyuronides were longer in transgenic fruits (61, 67.5 and 71 nm, in the control, antisense FaplC and antisense FaPG1 samples, respectively). Transgenic pectins showed a more complex structure, with a higher percentage of branched chains than the control, especially in the case of FaPG1 silenced fruits. Supramolecular pectin aggregates, supposedly formed by homogalacturonan and rhamnogalacturonan I, were more frequently observed in antisense FaPG1 samples. The larger modifications in the nanostructure of pectins in FaPG1 silenced fruits when compared with antisense pectate lyase plants correlate with the higher impact of polygalacturonase silencing on reducing strawberry fruit softening. PMID- 26256335 TI - Structural modification and characterization of bacterial cellulose-alginate composite scaffolds for tissue engineering. AB - A novel bacterial cellulose-alginate composite scaffold (N-BCA) was fabricated by freeze drying and subsequent crosslinking with Ca(2+). The N-BCA then underwent a second freeze drying step to remove water without altering the physical structure. A stable structure of N-BCA with open and highly interconnected pores in the range of 90-160 MUm was constructed. The N-BCA was stable in both water and PBS. The swelling ability of N-BCA in water was approximately 50 times its weight, which was about 6.5 times that of the freeze dried bacterial cellulose pellicles. N-BCA demonstrated no cytotoxicity against L929 mouse fibroblast cells. For long-term culture, N-BCA supported attachment, spreading, and proliferation of human gingival fibroblast (GF) on the surface. However, under static conditions, the cell migration and growth inside the scaffold were limited. Because of its biocompatibility and open macroporous structure, N-BCA could potentially be used as a scaffold for tissue engineering. PMID- 26256336 TI - Effects of kappa-carrageenan on rheological properties of dually modified sago starch: Towards finding gelatin alternative for hard capsules. AB - Composite sago starch-based system was developed and characterized with the aim to find an alternative to gelatin in the processing of pharmaceutical capsules. Dually modified (Hydrolyzed-Hydroxypropylated) sago starches were combined with kappa-carrageenan (0.25, 0.5, 0.75, and 1%). The rheological properties of the proposed composite system were measured and compared with gelatin as reference material. Results show that combination of HHSS12 (Hydrolysed-hydroxypropylated sago starch at 12h) with 0.5% kappa-carrageenan was comparable to gelatin rheological behavior in pharmaceutical capsule processing. The solution viscosity at 50 degrees C and sol-gel transition of the proposed composite system were comparable to those of gelatin. The viscoelastic moduli (G' and G") for the proposed system were lower than those of gelatin. These results illustrate that by manipulation of the constituents of sago starch-based composite system, a suitable alternative to gelatin can be produced with comparable properties and this could find potential application in pharmaceutical capsule industry. PMID- 26256337 TI - Preparation and characterization of antibacterial thiosemicarbazide chitosan as efficient Cu(II) adsorbent. AB - In the present work a method has been developed for the preparation of thiosemicarbazide-chitosan (TSCS) exploring the evaluation of enhanced adsorption of metal ions and antibacterial activities via derivatization. The splitting of carbon-carbon (C-2 and C-3) bond of vicinal diols of the chitosan chain is planned in a way to figure a "Schiff base intermediate" which undergoes the addition reaction in order to enhance total nitrogen and sulphur content for the chelation of Cu(II) ions from aqueous solutions in a batch adsorption system. Fourier transform infrared spectroscopy (FT-IR), (1)H NMR, elemental analysis (CHN analyzer), X-ray diffraction (XRD) and differential scanning calorimetric (DSC) analyses were used for the characterization of the end product. Surface morphologies were also studied by scanning electron microscopy (FESEM). The adsorption results showed that maximum adsorption was achieved at a dose concentration of 1.5 g/L, temperature of 25 degrees C with contact time of 20 min. The adsorption properties of TSCS toward Cu(II) ions were evaluated and found to be 99 +/- 1%. The antibacterial properties were evaluated against Escherichia coli bacteria confirming that the modified material (TSCS) possess enhanced antibacterial activities when compared with the virgin chitosan. PMID- 26256338 TI - Fabrication of mucoadhesive chitosan coated polyvinylpyrrolidone/cyclodextrin/clotrimazole sandwich patches for oral candidiasis. AB - This study aims to fabricate clotrimazole (CZ)-composite sandwich nanofibers using electrospinning. The CZ-loaded polyvinylpyrrolidone (PVP)/hydroxypropyl beta-cyclodextrin (HPbetaCD) fiber was coated with chitosan-cysteine (CS SH)/polyvinyl alcohol (PVA) to increase the mucoadhesive properties and to achieve a sustained release of the drug from the nanofibers. The nanofibers were characterized using scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) spectroscopy and X-ray diffractometry (XRD). The nanofibers mechanical and mucoadhesive properties, drug release, antifungal activity and cytotoxicity were also assessed. The fibers were in the nanoscale with good mucoadhesive properties. The XRPD revealed a molecular dispersion of amorphous CZ in the nanofibers. The initial fast release of CZ from the nanofibers was achieved. Moreover, the sandwich nanofibers coated for longer times resulted in slower release rates compared with the shorter coating times. The CZ-loaded nanofibers killed the Candida significantly faster than the commercial CZ lozenges at 5, 15 and 30 min and were safe for a 2-h incubation. Therefore, these nanofibers may be promising candidates for the treatment of oral candidiasis. PMID- 26256339 TI - Characterization and biological activities of a novel polysaccharide isolated from raspberry (Rubus idaeus L.) fruits. AB - A water-soluble polysaccharide namely RCP-II from raspberry fruits was obtained by complex enzyme method followed by successive purification using macroporous resin D4020 and Sephadex G-100 columns. RCP-II was an acidic heteropolysaccharide and the characteristic structure of polysaccharide was determined. The carbohydrate of RCP-II was composed with galacturonic acid, rhamnose, arabinose, xylose, glucose and galactose in a molar ratio of 1.00:0.55:1.19:0.52:0.44:1.90 and the average molecular weight was estimated to be 4013 Da, based on dextran standards. RCP-II presented high scavenging activity toward DPPH*, HO*, O2(*-) in a concentration-dependent manner. The determination of the inhibitory activity on protein glycation showed that in 14 days of incubation the inhibitory ability of RCP-II was more effective on the development of non-enzymatic glycation reaction at early phase than that at the following two phases. PMID- 26256340 TI - Synthesis and characterization of thiolated beta-cyclodextrin as a novel mucoadhesive excipient for intra-oral drug delivery. AB - The objective of the present study was to synthesize and characterize cysteamine conjugated beta-cyclodextrin (beta-CD-Cys) as a novel mucoadhesive oligomeric excipient for intra-oral drug delivery. beta-CD-Cys conjugates were obtained in a two-step synthetic pathway, whereby, vicinal diol groups of the oligomer were oxidized using increasing concentrations of sodium-per-iodate (NaIO4), prior to the covalent coupling of cysteamine via reductive amination. Quantification of immobilized thiol groups through Ellman's test revealed 561.56 +/- 81 MUmol/g, 1054.26 +/- 131 MUmol/g and 1783.92 +/- 201 MUmol/g of free thiol groups attached to the oligomer backbone depending on the extent of oxidation. beta-CD-Cys conjugates at concentrations of 0.5% (m/v) showed no toxic effects on Caco-2 cells within 72 h. Furthermore, beta-CD-Cys conjugates displayed a 4-fold improved water solubility compared to the parent oligomer. beta-CD-Cys conjugates (beta-CD-Cys561, beta-CD-Cys1054 and beta-CD-Cys1783) showed 2.86-, 15.09- and 49.08-fold improved retention time on porcine intestinal mucosa and 9.66-, 16.43- and 34.51-fold improved on the porcine buccal mucosa, respectively. Formation of inclusion complexes of miconazole nitrate and beta-CD-Cys1054 resulted in 150 fold increased solubility of miconazole nitrate. According to these results, it seems that beta-CD-Cys conjugates might provide a new promising tool for delivery of poorly water soluble therapeutic agents, such as miconazole nitrate for intra oral delivery. PMID- 26256341 TI - Strategies to improve the mechanical strength and water resistance of agar films for food packaging applications. AB - Agar films possess several properties adequate for food packaging applications. However, their high cost-production and quality variations caused by physiological and environmental factors affecting wild seaweeds make them less attractive for industries. In this work, native (NA) and alkali-modified (AA) agars obtained from sustainably grown seaweeds (integrated multi-trophic aquaculture) were mixed with locust bean gum (LBG) to make 'knife-coated' films with fixed final concentration (1 wt%) and variable agar/LBG ratios. Agar films were easier to process upon LBG addition (viscosity increase and gelling character decrease of the film-forming solutions observed by dynamic oscillatory and steady shear measurements). The mechanical properties and water resistance were optimal for films with 50 and/or 75% LBG contents and best in the case of NA (cheaper to extract). These findings can help reduce the cost-production of agar packaging films. Moreover, the controlled cultivation of seaweeds can provide continuous and reliable feedstock for transformation industries. PMID- 26256342 TI - Synthesis of the dendritic type beta-cyclodextrin on primary face via click reaction applicable as drug nanocarrier. AB - The objective of this study was the syntheses of well-defined glycodendrimer with entrapment efficiency by click reactions, with beta-cyclodextrins (beta-CDs) moiety to keep the biocompatibility properties, besides especially increase their capacity to load numerous appropriate sized guests. The original dendrimer containing beta-CD in both periphery and central was synthesized using click reaction. The entrapment property of the beta-CD-dendrimer was studied by methotrexate (MTX) drug. The chemical structure of beta-CD-dendrimer was characterized by (1)H NMR, (13)C NMR and FTIR and its inclusion complex structure were investigated by SEM, DLS, DSC and FTIR techniques. The cytotoxic effect of obtained compound and its inclusion complex with MTX was analyzed using MTT test. The MTT test exhibited that the synthesized compound was not cytotoxic to the cell line considered. The in vitro drug release study turned out that the obtained beta-CD dendrimer could be a suitable controlled drug delivery system for cancer treatment. PMID- 26256343 TI - Preparing cationic cotton linter cellulose with high substitution degree by ultrasonic treatment. AB - As an important cellulose derivative, cationic cellulose has becoming an attractive material. However, it remains challenging to produce cationic cellulose with high substitute degree. In this paper, we successfully increased the substitute degree of cationic cellulose by introducing ultrasonic treatment, which efficiently breaks hydrogen bonds of the chemical structure of cationic cellulose. Properties of cationic cellulose were studied by scanning electron spectroscope (SEM), contact angle, X-ray diffraction (XRD) and thermogravimetric analysis (TGA). Experimental results show that the cationic cellulose has rougher surface and lower crystallinity degree as compared to the original sample. TGA analysis verifies that the thermostability of CLC decreases after the cationic modification. The residual of the cationic cellulose (25 wt%) after pyrolysis increases significantly as compared to that of the original cellulose (15 wt%). PMID- 26256344 TI - Solution properties of a heteropolysaccharide extracted from pumpkin (Cucurbita pepo, lady godiva). AB - A water-soluble galactoglucofucomannan was extracted from pumpkin (Cucurbita pepo, lady godiva variety). GC-MS analysis indicated that the polysaccharide was composed of 1,6-linked-glucosyl, 1,2,6-linked-mannosyl, 1,3,6-linked-mannosyl, 1,2,6-linked-galactosyl, 1,2,6-linked-galactosyl, terminal fucosyl and terminal glucose. The solution properties of the polysaccharide were studied systematically by using size-exclusion chromatography combined with multi-angle laser light scattering, viscometry and dynamic light scattering at 25 degrees C. The weight average molecular masses (Mw), intrinsic viscosity [eta], radius of gyration (Rg) and hydrodynamic radius (Rh) were found to be 12.7 * 10(5)g/mol, 780 ml/g, 68 nm and 116 nm, respectively. The fraction dimension and value of rho (Rg/Rh) of the polysaccharide revealed that it existed in a sphere-like conformation in distilled water. The dependence of zero shear specific viscosity on the coil overlap parameter was analyzed using different models. Furthermore, degradation of samples upon autoclaving has been observed and quantified by intrinsic viscosity determination and SEC-MALLS. PMID- 26256345 TI - Catalytic actions of alkaline salts in reactions between 1,2,3,4 butanetetracarboxylic acid and cellulose: II. Esterification. AB - 1,2,3,4-Butanetetracarboxylic acid (BTCA) reacts with cellulose in two steps with catalysis of alkaline salts such as sodium hypophosphite: anhydride formation and esterification of anhydride with cellulose. The alkali metal ions were found effective in catalyzing formation of BTCA anhydride in a previous report. In this work, catalytic functions of the alkaline salts in the esterification reaction between BTCA anhydride and cellulose were investigated. Results revealed that acid anions play an important role in the esterification reaction by assisting removal of protons on intermediates and completion of the esterification between cellulose and BTCA. Besides, alkaline salts with lower pKa1 values of the corresponding acids are more effective ones for the reaction since addition of these salts could lead to lower pH values and higher acid anion concentrations in finishing baths. The mechanism explains the results of FTIR and wrinkle recovery angles of the fabrics cured under different temperatures and times. PMID- 26256346 TI - Changes in physicochemical properties and in vitro digestibility of common buckwheat starch by heat-moisture treatment and annealing. AB - Heat-moisture treatment (HMT) and annealing (ANN) were applied in the test to investigate how they can affect the physicochemical properties and in vitro digestibility of common buckwheat starch (CBS). In the practice, these two modification methods did not change typical 'A'-type X-ray diffraction pattern of CBS. However, the gelatinization temperature, amylose content, and relative crystallinity increased and peak viscosity value and gelatinization enthalpy of CBS declined significantly. Both the solubility and swelling power, which were temperature dependent, progressively decreased along with the treatments. Remarkable increase in slowly digested starch and resistant starch level was found at the same time. Besides, the decreases of rapidly digested starch and total hydrolysis content by using HMT were greater than by using ANN. The results indicated that the ANN and HMT efficiently modified physicochemical properties and in vitro digestibility of CBS and were able to improve its thermal stability, healthy benefits and application value. PMID- 26256347 TI - Pomelo peel modified with acetic anhydride and styrene as new sorbents for removal of oil pollution. AB - Pomelo peel (PP), as one of the well-known agricultural wastes, is cost-effective and environmentally friendly. Based on PP, two new kinds of oil sorbents were prepared by using acetic anhydride and styrene. The structures of raw pomelo peel (RP), acetic anhydride-treated pomelo peel (AP) and styrene-treated pomelo peel (SP) were characterized by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM), contact-angle (CA) measurements. The optimum reaction conditions for preparation of AP and SP were also investigated. The resulting products exhibited better oil sorption capacity than that of RP for diesel and lubricating oil, also SP had better oil sorption capacity than AP, while the oil sorption capacities of SP for diesel and lubricating oil reached 18.91 and 26.36 g/g, respectively. Adsorption kinetics was well described by the pseudo-second-order model. The results indicated that AP and SP, especially SP could be used as the substitute for non-biodegradable oil sorption materials. PMID- 26256348 TI - Cellulose acetate from oil palm empty fruit bunch via a one step heterogeneous acetylation. AB - Acetone soluble oil palm empty fruit bunch cellulose acetate (OPEFB-CA) of DS 2.52 has been successfully synthesized in a one-step heterogeneous acetylation of OPEFB cellulose without necessitating the hydrolysis stage. This has only been made possible by the mathematical modeling of the acetylation process by manipulating the variables of reaction time and acetic anhydride/cellulose ratio (RR). The obtained model was verified by experimental data with an error of less than 2.5%. NMR analysis showed that the distribution of the acetyl moiety among the three OH groups of cellulose indicates a preference at the C6 position, followed by C3 and C2. XRD revealed that OPEFB-CA is highly amorphous with a degree of crystallinity estimated to be ca. 6.41% as determined from DSC. The OPEFB-CA films exhibited good mechanical properties being their tensile strength and Young's modulus higher than those of the commercial CA. PMID- 26256349 TI - Preparation of reactive fibre interfaces using multifunctional cellulose derivatives. AB - Cellulose fibres have poor reactivity and limited potential for surface engineering with advanced chemical functionalization in water. In this work, cellulose fibres were decorated with azide functions by charge-directed self assembly of a novel water-soluble multifunctional cellulose derivative yielding reactive fibres. Propargylamine and 1-ethynylpyrene were utilized as a proof of concept that alkyne molecules may react with the azide functions of the reactive fibres via copper(I)-catalyzed azide-alkyne Huisgen cycloaddition (CuAAc) reaction in mild conditions. Chemical characterization of the fibres was carried out using classical techniques such as Raman-, fluorescence-, and UV-vis spectroscopy. Among other techniques, time-of-flight secondary ion mass spectrometry (ToF-SIMS), X-ray spectroscopy (XPS), two-photon microscopy (TPM), and inductively coupled plasma mass spectrometry (ICP-MS) were useful tools for additional characterization of the fibres decorated with amino- or photoactive groups. The information gathered in this work might contribute to the basis for the preparation of reactive cellulose-based interfaces with potential application in CuAAc reactions. PMID- 26256350 TI - Evaluation of bionanocomposites as packaging material on properties of soft white cheese during storage period. AB - Novel bionanocomposites based on chitosan/poly(vinyl alcohol)/titanium nanoparticles (CS/PVA/TiO2 nanocomposite) were prepared and used as packaging materials for soft white cheese. The prepared bionanocomposites were characterized using XRD, SEM, TEM and FT-IR. The CS/PVA/TiO2 bionanocomposites exhibited good mechanical properties. Furthermore, the obtained bionanocomposites exhibited superior antibacterial activity against gram positive (Staphylococcus aureus), gram negative (Pseudomonas aeruginosa, Escherichia coli) bacteria and fungi (Candidia albicans). The soft white cheese was manufactured and packaged within the CS/PVA/TiO2 nanocomposite films and stored at 7 degrees C for 30 days. The color, rheological and chemical properties of cheese were evaluated, also the influence of CS/PVA/TiO2 bionanocomposites on microbiological analysis of soft white cheese was assessed, the results indicated that the total bacterial counts, mold & yeast and coliform decreased with the increasing storage period and disappeared at the end of storage period compared with control. Consequently, CS/PVA/TiO2 bionanocomposite can be used in food packaging applications. PMID- 26256351 TI - Innovative production of bio-cellulose using a cell-free system derived from a single cell line. AB - The current study was intended to produce bio-cellulose through a cell-free system developed by disrupting Gluconacetobacter hansenii PJK through bead beating. Microscopic analysis indicated the complete disruption of cells (2.6 * 10(7) cells/mL) in 20 min that added 95.12 MUg/mL protein, 1.63 mM ATP, and 1.11 mM NADH into the medium. A liquid chromatography mass spectrometry/mass spectrometry linear trap quadrupole (LC-MS/MS LTQ) Orbitrap analysis of cell lysate confirmed the presence of all key enzymes for bio-cellulose synthesis. Under static conditions at 30 degrees C, microbial and cell-free systems produced 3.78 and 3.72 g/L cellulose, corresponding to 39.62 and 57.68% yield, respectively after 15 days. The improved yield based on consumed glucose indicated the superiority of cell-free system. Based on current findings and literature, we hypothesized a synthetic pathway for bio-cellulose synthesis in the cell-free system. This approach can overcome some limitations of cellulose producing cells and offers a wider scope for synthesizing cellulose composites with bactericidal elements through in situ synthesizing approaches. PMID- 26256352 TI - The efficient hemostatic effect of Antarctic krill chitosan is related to its hydration property. AB - Antarctic krill chitosan (A-Chitosan) was first evaluated in its hemostatic effect in this study. The prepared A-Chitosan powder showed low level of crystallinity and significantly high water binding capacity as 1293% (w/w). By mice tail amputation model and blood coagulation timing experiment, it is showed that this chitosan accelerated the tail hemostasis by 55% and shortened the blood clotting time by 38%. This efficacy was better than two other commercial chitosans investigated and was corresponding to their water binding capacities. Through examining the effect of chitosan on blood components, it could be found that platelets adhesion was mainly affected by the water binding capacity, and red blood cells aggregation was dependent on their deacetylation degree. The physicochemical properties resulted in better hydration property of chitosan would improve its hemostatic effect. These results suggested that Antarctic krill chitosan is a good candidate for hemostatic application. PMID- 26256353 TI - A simple procedure for preparing chitin oligomers through acetone precipitation after hydrolysis in concentrated hydrochloric acid. AB - Chitin oligomers are of interest because of their numerous biologically relevant properties. To prepare chitin oligomers containing 4-6 GlcNAc units [(GlcNAc)4 6], alpha- and beta-chitin were hydrolyzed with concentrated hydrochloric acid at 40 degrees C. The reactant was mixed with acetone to recover the acetone insoluble material, and (GlcNAc)4-6 was efficiently recovered after subsequent water extraction. Composition analysis using gel permeation chromatography and MALDI-TOF mass spectrometry indicated that (GlcNAc)4-6 could be isolated from the acetone-insoluble material with recoveries of approximately 17% and 21% from the starting alpha-chitin and beta-chitin, respectively. The acetone precipitation method is highly useful for recovering chitin oligomers from the acid hydrolysate of chitin. The changes in the molecular size and higher-order structure of chitin during the course of hydrolysis were also analyzed, and a model that explains the process of oligomer accumulation is proposed. PMID- 26256354 TI - Review on biomedical and bioengineering applications of cellulose sulfate. AB - Polysaccharide sulfates are naturally existing chemicals that show important biological activities in living organisms. Cellulose sulfate is a semi synthesized polysaccharide sulfate with a relatively simple chain structure and unique biological properties and its biological applications have been explored in research and clinical trials. With the advance of cellulose derivatization and characterization, cellulose sulfate molecules with tailored structures have been developed to fulfill individual requirements. This review aims to provide a summary of recent development of cellulose sulfate in biomedical applications. Its synthesis pathways were discussed with structure-property relationship elucidated. The application of cellulose sulfate in drug delivery and microbe/cell immobilization were summarized with emphasis given on its polyelectrolyte complex formation processes. PMID- 26256355 TI - Antitumor and immunomodulatory activities of a water-soluble polysaccharide from Chaenomeles speciosa. AB - In this study, a water-soluble polysaccharide (CSP) was successfully purified from Chaenomeles speciosa by DEAE-Sepharose and Sephadex G-100 column chromatography. CSP had a weight-average molecular weight of about 6.3 * 10(4)Da and was composed of glucose (Glc), galactose (Gal), rhamnose (Rha) and arabinose (Ara) with a relative molar ratio of 4.6:1.3:0.8:0.5. CSP could not only inhibit the growth of S180 tumor transplanted in mice, but also increase the relative spleen index and body weight of tumor bearing mice. Moreover, concanavalin A (ConA) and lipopolysaccharide (LPS) induced splenocyte proliferation and peritoneal macrophage phagocytosis were also enhanced after CSP administration. Furthermore, CSP treatment could improve delayed type hypersensitivity (DTH) and promote the secretion of IL-2, TNF-alpha and IFN-gamma in serum. The overall findings suggest that the antitumor effect of CSP is might be associated with its potent immunostimulatory activity. PMID- 26256356 TI - Fabrication of interpenetrating polymer network chitosan/gelatin porous materials and study on dye adsorption properties. AB - One kind of adsorbent based on chitosan and gelatin with interpenetrating polymer networks (IPN) and porous dual structures was prepared using genipin as the cross linker. These dual structures were demonstrated by means of Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). Adsorptions of acid orange II dye from aqueous solution were carried out at different genipin contents, adsorption times and pH values. The results showed that this material was put up the largest adsorption capacity when the genipin content is 0.25 mmol/L, meanwhile, the lower the solution pH value the greater the adsorption capacity. The chitosan/gelatin interpenetrating polymer networks porous material displayed pH-sensitive and rapidly response in adsorption and desorption to pH altered. It is indicated that the cross-linked chitosan/gelatin interpenetrating polymer networks porous material could be used as a recyclable adsorbent in removal or separation of anionic dyes as environmental pH condition changed. PMID- 26256357 TI - Bacillus subtilis 168 levansucrase (SacB) activity affects average levan molecular weight. AB - Levan is a fructan polymer that offers a variety of applications in the chemical, health, cosmetic and food industries. Most of the levan applications depend on levan molecular weight, which in turn depends on the source of the synthesizing enzyme and/or on reaction conditions. Here we demonstrate that in the particular case of levansucrase from Bacillus subtilis 168, enzyme concentration is also a factor defining the molecular weight levan distribution. While a bimodal distribution has been reported at the usual enzyme concentrations (1 U/ml equivalent to 0.1 MUM levansucrase) we found that a low molecular weight normal distribution is solely obtained al high enzyme concentrations (>5 U/ml equivalent to 0.5 MUM levansucrase) while a high normal molecular weight distribution is synthesized at low enzyme doses (0.1 U/ml equivalent to 0.01 MUM of levansucrase). PMID- 26256358 TI - Facile fabrication of mesoporous poly(ethylene-co-vinyl alcohol)/chitosan blend monoliths. AB - Poly(ethylene-co-vinyl alcohol) (EVOH)/chitosan blend monoliths were fabricated by thermally-induced phase separation method. Chitosan was successfully incorporated into the polymeric monolith by selecting EVOH as the main component of the monolith. SEM images exhibit that the chitosan was located on the inner surface of the monolith. Fourier-transform infrared analysis and elemental analysis indicate the successful blend of EVOH and chitosan. BET results show that the blend monoliths had high specific surface area and uniform mesopore structure. Good adsorption ability toward various heavy metal ions was found in the blend monoliths due to the large chelation capacity of chitosan. The blend monoliths have potential application for waste water purification or bio-related applications. PMID- 26256359 TI - Development of silver sulfadiazine loaded bacterial cellulose/sodium alginate composite films with enhanced antibacterial property. AB - Sodium alginate (SA) and bacterial cellulose (BC) are widely used in many applications such as scaffolds and wound dressings due to its biocompatibility. Silver sulfadiazine (AgSD) is a topical antibacterial agents used as a topical cream on burns. In the study, novel BC/SA-AgSD composites were prepared and characterized by SEM, FTIR and TG analyses. These results indicate AgSD successfully impregnated into BC/SA matrix. The swelling behaviors in different pH were studied and the results showed pH-responsive swelling behaviors. The antibacterial performances of BC/SA-AgSD composites were evaluated with Escherichia coli, Staphylococcus aureus and Candida albicans. Moreover, the cytotoxicity of BC/SA-AgSD composites was performed on HEK 293 cells. The experimental results showed BC/SA-AgSD composites have excellent antibacterial activities and good biocompatibility, thus confirming its utility as potential wound dressings. PMID- 26256360 TI - Accumulation of recalcitrant xylan in mushroom-compost is due to a lack of xylan substituent removing enzyme activities of Agaricus bisporus. AB - The ability of Agaricus bisporus to degrade xylan in wheat straw based compost during mushroom formation is unclear. In this paper, xylan was extracted from the compost with water, 1M and 4M alkali. Over the phases analyzed, the remaining xylan was increasingly substituted with (4-O-methyl-)glucuronic acid and arabinosyl residues, both one and two arabinosyl residues per xylosyl residue remained. In the 1M and 4M KOH soluble solids of spent compost, 33 and 49 out of 100 xylosyl residues, respectively, were substituted. The accumulation of glucuronic acid substituents matched with the analysis that the two A. bisporus genes encoding for alpha-glucuronidase activity (both GH115) were not expressed in the A. bisporus mycelium in the compost during fruiting. Also, in a maximum likelihood tree it was shown that it is not likely that A. bisporus possesses genes encoding for the activity to remove arabinose from xylosyl residues having two arabinosyl residues. PMID- 26256361 TI - Design and characterization of chitosan-based composite particles with tunable interfacial properties. AB - Composite nano-microparticles were prepared in aqueous solution that contain chitosan or modified (carboxymethyl) chitosan with polyanion species such as alginate or tripolyphosphate, respectively. Several types of particles were prepared and characterized by (1)H/(31)P NMR spectroscopy, IR spectroscopy, and DLS. According to DLS, the particle size was observed to increase as the concentration of the aqueous urea solution increased. The average size and polydispersity index (in parentheses) vary and are reported for the chitosan based particles from 243.0 +/- 1 nm (0.28) to 424 +/- 14 nm (0.33), according to DLS measurements at ambient conditions. Thus, the particles are herein referred to as nano-microparticles (NMPs) due to the relative size range. The stability of the NMPs is related to the particle composition and the aqueous solution conditions, as evidenced by variable NMP stability on the order of two weeks or more at different ionic strength. PMID- 26256362 TI - Structure-function relationships of immunostimulatory polysaccharides: A review. AB - Immunostimulatory polysaccharides are compounds capable of interacting with the immune system and enhance specific mechanisms of the host response. Glucans, mannans, pectic polysaccharides, arabinogalactans, fucoidans, galactans, hyaluronans, fructans, and xylans are polysaccharides with reported immunostimulatory activity. The structural features that have been related with such activity are the monosaccharide and glycosidic-linkage composition, conformation, molecular weight, functional groups, and branching characteristics. However, the establishment of structure-function relationships is possible only if purified and characterized polysaccharides are used and selective structural modifications performed. Aiming at contributing to the definition of the structure-function relationships necessary to design immunostimulatory polysaccharides with potential for preventive or therapeutical purposes or to be recognized as health-improving ingredients in functional foods, this review introduces basic immunological concepts required to understand the mechanisms that rule the potential claimed immunostimulatory activity of polysaccharides and critically presents a literature survey on the structural features of the polysaccharides and reported immunostimulatory activity. PMID- 26256363 TI - Comparison of the preliminary characterizations and antioxidant properties of polysaccharides obtained from Phellinus baumii growth on different culture substrates. AB - Three polysaccharides (PPB-MB, PPB-MW and PPB-MM) were obtained from the fruiting body of Phellinus baumii growth on different culture substrates (mulberry branches, mixed wood sawdust and an equal combination of the two materials) and their chemical composition was investigated. PPB-MM contained the highest contents of neutral sugar (66.59%) and uronic acid (23.38%), followed by PPB-MW and PPB-MB, with PPB-MW having the highest protein content. The three polysaccharides were all composed of six kinds of monosaccharides, namely fucose, mannose, glactose, xylose, arabinose and glucose. The antioxidant activities of the three polysaccharides were determined using lipid peroxidant inhibition, ABTS radical scavenging, and Fe(2+)-chelating assay. Results showed that PPB-MM exhibited the highest antioxidant properties in all the assays. As a result, an equal combination of mulberry branches and mixed wood sawdust serves as a good culture substrate for producing such antioxidant polysaccharides. PMID- 26256364 TI - In situ synthesis of bacterial cellulose/polycaprolactone blends for hot pressing nanocomposite films production. AB - A series of bacterial cellulose (BC)/polycaprolactone (PCL) nanocomposite films were successfully prepared by supplementation of the BC culture medium with variable amounts of PCL powder followed by hot-pressing of the BC/PCL mixtures obtained after incubation. PCL powder was fully incorporated into the BC network during its production and did not change the BC network morphology. The obtained films showed a homogenous distribution of PCL throughout the BC network, as well as good thermal stability (up to 200 degrees C) and improved mechanical properties, when compared to pristine PCL. In addition, the intrinsic biodegradability and biocompatibility of the nanocellulose fibers and PCL opens the possibility of using this novel nanocomposite in the biomedical field and food packaging. The BC biosynthetic approach combined with the hot-pressing proved successful for the sustainable development of nanocomposites combining hydrophobic thermoplastic matrices and hydrophilic nanocellulose fibers, without the use of harmful organic solvents commonly used to dissolve this type of polymeric matrices. PMID- 26256365 TI - Synergistic amylomaltase and branching enzyme catalysis to suppress cassava starch digestibility. AB - Starch provides our main dietary caloric intake and over-consumption of starch containing foods results in escalating life-style disease including diabetes. By increasing the content of alpha-1,6 branch points in starch, digestibility by human amylolytic enzymes is expected to be retarded. Aiming at generating a soluble and slowly digestible starch by increasing the content and changing the relative positioning of the branch points in the starch molecules, we treated cassava starch with amylomaltase (AM) and branching enzyme (BE). We performed a detailed molecular analysis of the products including amylopectin chain length distribution, content of alpha-1,6 glucosidic linkages, absolute molecular weight distribution and digestibility. Step-by-step enzyme catalysis was the most efficient treatment, and it generated branch structures even more extreme than those of glycogen. All AM- and BE-treated samples showed increased resistance to degradation by porcine pancreatic alpha-amylase and glucoamylase as compared to cassava starch. The amylolytic products showed chain lengths and branching patterns similar to the products obtained from glycogen. Our data demonstrate that combinatorial enzyme catalysis provides a strategy to generate potential novel soluble alpha-glucan ingredients with low dietary digestibility assets. PMID- 26256366 TI - Unusual effects of monocarboxylic acids on the structure and on the transport and mechanical properties of chitosan films. AB - The purpose of this study was to study the transport of monocarboxylic acids in chitosan films, since this is important for understanding and predicting the drying kinetics of chitosan from aqueous solutions. Despite the wealth of data on chitosan films prepared from aqueous monocarboxylic acid solutions, this transport has not been reported. Chitosan films were exposed to formic, acetic, propionic and butyric acid vapours, it was found that the rate of uptake decreased with increasing molecular size. The equilibration time was unexpectedly long, especially for propionic and butyric acid, nine months. A clear two-stage uptake curve was observed for propionic acid. Evidently, the rate of uptake was determined by acid-induced changes in the material. X-ray diffraction and infrared spectroscopy indicated that the structure of the chitosan acetate and buffered chitosan films changed during exposure to acid and during the subsequent drying. The dried films previously exposed to the acid showed less crystalline features than the original material and a novel repeating structure possibly involving acid molecules. The molar mass of the chitosan decreased on exposure to acid but tensile tests revealed that the films were always ductile. The films exposed to acid vapour (propionic and butyric acid) for the longest period of time were insoluble in the size-exclusion chromatography eluent, and they were also the most ductile/extensible of all samples studied. PMID- 26256367 TI - Improving the hydrogen peroxide bleaching efficiency of aspen chemithermomechanical pulp by using chitosan. AB - The presence of transition metals during the hydrogen peroxide bleaching of pulp results in the decomposition of hydrogen peroxide, which decreases the bleaching efficiency. In this study, chitosans were used as peroxide stabilizer in the alkaline hydrogen peroxide bleaching of aspen chemithermomechanical pulp (CTMP). The results showed that the brightness of the bleached CTMP increased 1.5% ISO by addition of 0.1% chitosan with 95% degree of deacetylation during peroxide bleaching. Transition metals in the form of ions or metal colloid particles, such as iron, copper and manganese, could be adsorbed by chitosans. Chitosans could inhibit the decomposition of hydrogen peroxide catalyzed by different transition metals under alkaline conditions. The ability of chitosans to inhibit peroxide decomposition depended on the type of transition metals, chitosan concentration and degree of deacetylation applied. The addition of chitosan slightly reduced the concentration of the hydroxyl radical formed during the hydrogen peroxide bleaching of aspen CTMP. PMID- 26256368 TI - One-pot beta-cyclodextrin-assisted extraction of active ingredients from Xue-Zhi Ning basing its encapsulated ability. AB - Xue-Zhi-Ning (XZN) is a traditional Chinese medicine formula, containing active ingredients with poor solubility in water, which has been demonstrated to be helpful for patients with hyperlipidemia. One-pot beta-cyclodextrin (beta-CD) assisted extraction of active ingredients from XZN has been carried out to develop an efficient and eco-friendly extraction process. Five active compounds- rubrofusarin gentiobioside, 2,3,5,4'-tetrahydroxy-stilbene-2-O-beta-D-glucoside, emodin, nuciferine and quercetin--were identified by UPLC/DAD/MS and used as indexes to evaluate the process optimized by an orthogonal test. The results showed that addition of beta-CD significantly enhanced the extraction ratios of all five components. The enhancement of extraction ratios was positively correlated with the apparent formation constants between beta-CD and the compounds. The study also showed that the stabilities and dissolution rates of the active ingredients were improved in the presence of beta-CD. This one-pot beta-cyclodextrin-assisted extraction has the potential to be applied in pharmaceutical preparations directly. PMID- 26256369 TI - Cellulose based cationic adsorbent fabricated via radiation grafting process for treatment of dyes waste water. AB - A cationized adsorbent was prepared from cellulosic cotton fabric waste via a single step-green-radiation grafting process using gamma radiation source, wherein poly[2-(methacryloyloxy) ethyl]trimethylammonium chloride (PMAETC) was covalently attached to cotton cellulose substrate. Radiation grafted (PMAETC-g cellulose) adsorbent was investigated for removal of acid dyes from aqueous solutions using two model dyes: Acid Blue 25 (AB25) and Acid Blue 74 (AB74). The equilibrium adsorption data was analyzed by Langmuir and Freundlich isotherms, whereas kinetic data was analyzed by pseudo first order, pseudo second order, intra particle diffusion and Boyd's models. The PMAETC-g-cellulose adsorbent with 25% grafting yield exhibited equilibrium adsorption capacities of ~ 540.0mg/g and ~ 340.0mg/g for AB25 and AB74, respectively. Linear and nonlinear fitting of adsorption data suggested that the equilibrium adsorption process followed Langmuir adsorption isotherm model, whereas, the kinetic adsorption process followed pseudo-second order model. The multi-linearities observed in the intra particle kinetic plots suggested that the intraparticle diffusion was not the only rate-controlling process in the adsorption of acid dyes on the adsorbent, which was further supported by Boyd's model. The adsorbent could be regenerated by eluting the adsorbed dye from the adsorbent and could be repeatedly used. PMID- 26256370 TI - Production of structurally diverse wheat arabinoxylan hydrolyzates using combinations of xylanase and arabinofuranosidase. AB - Structurally different wheat arabinoxylan hydrolyzates (AXH) were generated using different combinations of Cellvibrio japonicas xylanase (CJX), Aspergillus niger xylanase (ANX), Bifidobacterium adolescentis arabinofuranosidase (BAF) and Clostridium thermocellum arabinofuranosidase (CAF). Between the two xylanases, ANX might be an enzyme of choice for the production of AXH with simple structural details while CJX might be selected for the production of AXH with more complex structural features. Addition of BAF followed by CAF is more effective in generating AXH with higher amount of unsubstituted xylose. CJX series resulted in lower molecular weights compared to ANX series. The information derived about the capabilities of the two xylanases and two arabinofuranosidase could provide important information in decision making regarding enzymes to be used to generate AXH with specific structural details. Such hydrolyzates could be useful as substrate for future research exploring the effect of fine structural details in AXH on their biological and physical properties. PMID- 26256371 TI - Behaviour of cyanidin-3-glucoside, beta-lactoglobulin and polysaccharides nanoparticles in bulk and oil-in-water interfaces. AB - Particle size distributions as well the interfacial and rheological properties of the films at the oil/water interface were used to study the effect of the interacting system between beta-lactoglobulin, cyanidin-3-glucoside and pectin or chitosan in buffer solutions. The particles obtained were smaller with cy-3-gluc beta-lg-pectin and had reduced polydispersity with cy-3-gluc-beta-lg-chitosan. Based on time dependent surface pressure results, beta-lg-pectin mixtures showed a slower increase at the beginning of the measurement, while beta-lg-chitosan mixtures showed no differences with beta-lg alone. Contrarily, dilatational properties increased for ternary chitosan mixtures, but they remained similar to the pure protein in ternary pectin mixtures. Cy-3-gluc interfacial properties were reduced by the presence of pectin and chitosan. The interactions between cy 3-gluc and the biopolymers that have been selected in the present work resulted in a lower content of free polyphenol, reduced antioxidant properties as well as free beta-lg. The impact of this effect was more relevant when pectin was used. PMID- 26256373 TI - Investigation of physical and biological properties of polypyrrole nanotubes chitosan nanocomposites. AB - Polypyrrole nanotubes-chitosan (PPy-NTs:chitosan) nanocomposite films have been synthesized with varying concentration of polypyrrole nanotubes (PPy-NTs) and their physical and biological properties have been investigated. Scanning electron microscopy (SEM) micrographs exhibit the increase in surface roughness of the nanocomposite films with increasing concentration of PPy-NTs. Enhancement in hydrophilicity of the nanocomposite films has been observed after surface functionalization with glutaraldehyde which is attributed to increase in surface energy due to the incorporation of polar groups on the films surface. The increasing amount of PPy-NTs in the nanocomposite leads to an increase in haemolysis activity, while the treatment with glutaraldehyde results in the decrease in haemolysis activity giving rise to higher biocompatibility. Urease immobilization in glutaraldehyde treated films exhibits higher enzymatic activity as compared to that of the untreated films, which is attributed to the enhancement in hydrophilicity and biocompatibility of the PPy-NTs:chitosan nanocomposites after functionalization with glutaraldehyde. PMID- 26256372 TI - Investigating triazine-based modification of hyaluronan using statistical designs. AB - Hyaluronan (HA) and its derivatives have been extensively researched for many biomedical applications. To precisely tailor the property of HA by derivatizing it to a pre-determined extent is challenging, yet critical. In this paper, we used 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) and N-methylmorpholine (NMM) to derivatize HA via a triazine-based coupling reaction. Using a fractional factorial (FF) design, we observed that water content in the solvent, and molar ratios of CDMT and NaHCO3 to the carboxylate were the significant factors controlling the derivatization. We investigated how the effect of each factor changes as reaction conditions change. Moreover, by altering the amount of CDMT and NaHCO3, we developed a cubic regression model for precise control of the extent of derivatization using a response surface methodology (RSM) with a D optimal design. No spurious peaks were detected by (1)H NMR spectrum and only 10% decrease of molecular weight of the derivatized HA was determined by GPC. The HA with 6% modification was relatively biocompatible up to 15 mg/mL. PMID- 26256374 TI - Injectable thermo-responsive hydrogel composed of xanthan gum and methylcellulose double networks with shear-thinning property. AB - Injectable hydrogel precursor solution was prepared by physical blend of xanthan gum (XG) and methylcellulose (MC) in aqueous solution. Due to the formation of XG network composed of XG double helical strand structure, XG/MC blend was a high viscous solution with good shear-thinning property at room temperature. When the temperature was changed from 23 to 37 degrees C, thermo-responsive MC network formed, which caused XG/MC blend solution to gelate. The gelation time and storage modulus of the blend can be tuned by XG and/or MC concentrations. Both in vitro and in vivo investigations revealed that the blend solution immediately recovered its high viscosity and rapidly formed hydrogel at body temperature after injection using a syringe. In vivo biocompatibility and biodegradability of the hydrogel were validated by implantation of the hydrogel in rats. In vitro investigation demonstrated that XG/MC blend is a promising injectable hydrogel material for long-term drug delivery. PMID- 26256375 TI - Thermal properties of frozen water in the native and amorphous starches with various hydration degrees. AB - The melting process of frozen water (FW) in various starches (rice, wheat, potato) that have crystal lattices of A- and B-type has been studied by means of differential scanning calorimetry (DSC). The dependences of the melting temperature (Tm) and heat (Qm) of FW on the size of the water clusters forming in starches with various humidity (the so-called size effect) and on conformational changes of starch molecules upon the destruction of native starch crystals (starch amorphization) have been considered. It has been found that in the native starches with low humidity (<35%) the Tm of FW lies below 0 degrees C and decreases with the decrease of their humidity. The sizes of the water clusters formed under these conditions have been estimated. In contrast, such a size effect in amorphous starches has not been observed and possible reasons for its masking have been discussed. Still, all the values of Tm for FW obtained in the amorphous starches are also negative thereby indicating the dispersed state of water in these systems. Conversely, the size effect for Qm of FW in starches with low humidity, very pronounced in the amorphous state and barely visible in the native one, has been found. It has been established that the starch amorphization leads to a redistribution of the relative amounts of FW and unfrozen water (UFW) resulting in the decrease of Qm for FW in both A- and B- starch types. Finally, it has been concluded that in all the investigated starches there exist water clusters with Tm and Qm lower than that of bulk water. PMID- 26256376 TI - Physicochemical and functional properties of dietary fiber from maca (Lepidium meyenii Walp.) liquor residue. AB - Using maca (Lepidium meyenii) liquor residue as the raw material, dietary fiber (DF) was prepared by chemical (MCDF) and enzymatic (MEDF) methods, respectively, of which the physicochemical and functional properties were comparatively studied. High contents of DF were found in MCDF (55.63%) and MEDF (81.10%). Both fibers showed good functional properties, including swelling capacity, water holding capacity, oil holding capacity, glucose adsorption capacity and glucose retardation index. MEDF showed better functional properties, which could be attributed to its higher content of DF, more irregular surface and more abundant monosaccharide composition. The results herein suggest that maca DF prepared by enzymatic method from liquor residue is a good functional ingredient in food products. PMID- 26256377 TI - Characterization of cellulose from banana pseudo-stem by heterogeneous liquefaction. AB - A cellulose extraction from banana pseudo-stem through the combination of bleach and liquefaction processes was described: holocellulose was isolated by the sodium chlorite method, and then the cellulose was obtained by removing the hemicellulose through chemical liquefaction. The chemical composition, morphology, thermal properties and degree of crystallinity of the celluloses were characterized to discuss their suitability for new bio-based composite materials. It was shown that hemicellulose can be selectively liquefied to get cellulose. The hemicellulose content in cellulose is decreased from 45.69% to 8.38%. Surface morphological studies revealed that there is a reduction in fiber diameter and fiber bundles are divided into individual fibrils, which lead to an increase of the surface area and results in an increased adhesion at the fiber-matrix interface in composites. Thermal analysis results show that the cellulose exhibit enhanced thermal stability over holocellulose. XRD results indicate that the crystallinity is increased from 52.22% to 81.26% by liquefaction. PMID- 26256378 TI - Photo-responsive shell cross-linked micelles based on carboxymethyl chitosan and their application in controlled release of pesticide. AB - An amphiphilic carboxymethyl chitosan conjugate with photolabile 2-nitrobenzyl side groups (NBS-CMCS) was synthesized, which could self-assemble into polymeric micelles in aqueous condition following by adding dropwise dialdehyde to form a cross-linking structure. TEM and (1)H NMR confirmed that the cross-linked micelles had a core-shell configuration with an average diameter of 140 +/- 5.5 nm. DLS and TEM observations showed that the cross-linked micelles were stable in aqueous solution at pH 7.0 without light irradiation, while they could transfer into nanocapsules upon exposure to 365 nm UV light. Diuron, a photosynthetic inhibitor, was encapsulated in the cross-linked micelles reaching encapsulation efficiency as much as 91.9%. No release of the encapsulated diuron was detected without light, whereas a release rate as high as 96.8% over 8h at pH 7.0 buffer was observed under solar stimulated irradiation, indicating that the cross-linked micelles may be used as a photo-controlled sustained release carrier for the delivery of photosynthetic inhibitor. PMID- 26256379 TI - Isolation of barley hulls and straw constituents and study of emulsifying properties of their arabinoxylans. AB - Both barley hulls and straw contain valuable arabinoxylans and other useful carbohydrate and non-carbohydrate components. The functional water soluble non caloric arabinoxylan (hemicellulose B) fraction was isolated from hot water extracted and de-starched barley hulls and straws by an alkaline hydrogen peroxide extraction followed by ethanol precipitation. Barley hulls contained comparatively more Hemi. B (20.51%) than barley straws (7.41 to 12.94%). The sugar composition of Hemi. B showed that they were typical arabinoxylans containing (in addition to arabinose and xylose) some galactose, glucose and acidic sugars in the side chains. The hemicellulose B fractions from barley straws were superior oil-in-water emulsifiers than those from barley hulls. These Hemi. B fractions contain protein, which contributes to their emulsions stabilizing property. PMID- 26256380 TI - Chitosan/pectin polyelectrolyte complex as a pH indicator. AB - A polyelectrolyte complex (PEC) matrix formed between chitosan and pectin was developed to entrap a bioactive compound (anthocyanin), obtaining an useful pH indicator device. Polysaccharides of opposite charges such as chitosan and pectin can have a very strong intermolecular interaction. The innovation lies in obtaining a new system based on natural and biodegradable compounds, which is simple to manufacture, to indicate variation in pH by visual changes in colour. This device has potential applications in food packaging. The PEC was studied using chitosan and pectin solutions at different pHs values (3.0, 4.0, 5.0 and 5.5) and pectin/chitosan molar ratios (1.0 to 10/1.0 to 5.0). PEC films were homogeneous and showed the highest yield (60.0%) at pH 5.5. Diffusion tests indicated efficient bioactive compound entrapment in the PEC matrix. Thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy indicate the compatibility between the polymers and bioactive compound. PMID- 26256381 TI - Rhamnogalacturonan I containing homogalacturonan inhibits colon cancer cell proliferation by decreasing ICAM1 expression. AB - Pectin modified with pH, heat or enzymes, has previously been shown to exhibit anti-cancer activity. However, the structural requirements for modified pectin bioactivity have rarely been addressed. In this study several pectin extracts representing different structural components of pectin were assessed for effects against colon cancer cells. Rhamnogalacturonan I (RGI) extracts reduced proliferation of DLD1 and HCT116 colon cancer cells in a dose- and time-dependent manner. RGI reduced ICAM1 gene expression and siRNA-mediated knockdown of ICAM1 expression decreased cell proliferation providing a potential novel mechanism for the anti-cancer activity of pectin. Structural analysis of bioactive and non bioactive RGIs suggested that a homogalacturonan component is maybe essential for the anti-proliferative activity, furthering the understanding of the structural requirements for pectin bioactivity. PMID- 26256382 TI - Noble metal/functionalized cellulose nanofiber composites for catalytic applications. AB - In this study, cellulose acetate nanofibers (CANFs) with a mean diameter of 325 +/- 2.0 nm were electrospun followed by deacetylation and functionalization to produce anionic cellulose nanofibers (f-CNFs). The noble metal nanoparticles (RuNPs and AgNPs) were successfully decorated on the f-CNFs by a simple wet reduction method using NaBH4 as a reducing agent. TEM and SEM images of the nanocomposites (RuNPs/CNFs and AgNPs/CNFs) confirmed that the very fine RuNPs or AgNPs were homogeneously dispersed on the surface of f-CNFs. The weight percentage of the Ru and Ag in the nanocomposites was found to be 13.29 wt% and 22.60 wt% respectively; as confirmed by SEM-EDS analysis. The metallic state of the Ru and Ag in the nanocomposites was confirmed by XPS and XRD analyses. The usefulness of these nanocomposites was realized from their superior catalytic activity. In the aerobic oxidation of benzyl alcohol to benzaldehyde, the RuNPs/CNFs system gave a better yield of 89% with 100% selectivity. Similarly, the AgNPs/CNFs produced an excellent yield of 99% (100% selectivity) in the aza Michael reaction of 1-phenylpiperazine with acrylonitrile. Mechanism has been proposed for the catalytic systems. PMID- 26256383 TI - Synthesis of amide-functionalized cellulose esters by olefin cross-metathesis. AB - Cellulose esters with amide functionalities were synthesized by cross-metathesis (CM) reaction of terminally olefinic esters with different acrylamides, catalyzed by Hoveyda-Grubbs 2nd generation catalyst. Chelation by amides of the catalyst ruthenium center caused low conversions using conventional solvents. The effects of both solvent and structure of acrylamide on reaction conversion were investigated. While the inherent tendency of acrylamides to chelate Ru is governed by the acrylamide N-substituents, employing acetic acid as a solvent significantly improved the conversion of certain acrylamides, from 50% to up to 99%. Homogeneous hydrogenation using p-toluenesulfonyl hydrazide successfully eliminated the alpha,beta-unsaturation of the CM products to give stable amide functionalized cellulose esters. The amide-functionalized product showed higher Tg than its starting terminally olefinic counterpart, which may have resulted from strong hydrogen bonding interactions of the amide functional groups. PMID- 26256384 TI - Synthesis and antioxidant properties of chitosan and carboxymethyl chitosan stabilized selenium nanoparticles. AB - Monodispersible selenium nanoparticles (SeNPs) were synthesized by using chitosan (CS) and carboxymethyl chitosan (CCS) as the stabilizer and capping agent using a facile synthetic approach. The structure, size, morphology and antioxidant activity of the nanocomposites were characterized by transmission electron microscopy (TEM), Ultraviolet-visible spectroscopy (UV-vis), Dynamic Light Scattering (DLS), Fourier transform infrared (FTIR), Thermogravimetric analysis (TGA). The results revealed that the monodispersible SeNPs (mean particle size of about 50 nm) were ligated with CS and CCS to form nanocomposites in aqueous solution for at least 30 days, and for 120 days the nanoparticles increased to 180 nm or so in size. The DPPH scavenging ability of CS-SeNPs was higher than that of CCS-SeNPs, and could reach 93.5% at a concentration of 0.6 mmol/L. Moreover, SeNPs, CS-SeNPs and CCS-SeNPs exhibited a higher ABTS scavenging ability in comparison to Na2SeO3. PMID- 26256385 TI - Particulate structure of phytoglycogen studied using beta-amylolysis. AB - Phytoglycogen (PG), a dendrimer-like glucan particulate, has a much higher dispersed molecular density than amylopectin (AP). In this study, beta-amylase was used to investigate the effect of high molecular density of PG on its susceptibility to enzymatic hydrolysis. AP and PG reached the limit of beta amylolysis at 20 and 480 min, respectively, suggesting a much higher resistance of PG to beta-amylase. The majority of PG beta-amylolysis occurred in the initial 2 min, followed by a slow progression that implied low accessibility of internal particulate portion to enzyme. The chain length profile of PG beta-limit dextrin showed only one population of long chains, indicating the absence of branch clusters with PG. At the limit of beta-amylolysis, a substantial decrease in the molar mass was observed for both PG and AP, whereas only a slight reduction in the Z-average root mean square radius was observed for PG (from 24.5 to 23.1 nm) compared to that of AP (from 91.1 to 69.6 nm). PMID- 26256386 TI - Fabrication of tethered carbon nanotubes in cellulose acetate/polyethylene glycol 400 composite membranes for reverse osmosis. AB - In this study pristine multi-walled carbon nanotubes (MWCNTs) were surface engineered (SE) in strong acidic medium by oxidation purification method to form SE-MWCNT. Five different amount of SE-MWCNT ranging from 0.1 to 0.5 wt% were thoroughly and uniformly dispersed in cellulose acetate/polyethylene glycol (CA/PEG400) polymer matrix during synthesis of membrane by dissolution casting method. The structural analysis, surface morphology and roughness was carried out by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and atomic force microscopy (AFM), respectively, which showed that the dispersed SE-MWCNT was substantially tethered in CA/PEG400 polymer matrix membrane. The thermogravimetric analysis (TGA) of membranes also suggested some improvement in thermal properties with the addition of SE-MWCNT. Finally, the performance of these membranes was assessed for suitability in drinking water treatment. The permeation flux and salt rejection were determined by using indigenously fabricated reverse osmosis pilot plant with 1000 ppm NaCl feed solution. The results showed that the tethered SE-MWCNT/CA/PEG400 polymer matrix membrane, with strong SE-MWCNTs/polymer matrix interaction, improved the salt rejection performance of the membrane with the salt rejection of 99.8% for the highest content of SE-MWCNT. PMID- 26256387 TI - Cationic amphiphilic microfibrillated cellulose (MFC) for potential use for bile acid sorption. AB - In this work, Micro-fibrillated Cellulose (MFC) was cationically modified by quaternary ammonium groups with different chemical structures aiming to improve the sorption capacity to bile acid. The in-vitro bile acid sorption was performed by investigating various factors, such as quaternary ammonium group content and length of its alkyl substituent of the modified cationic MFC (CMFC), ionic strength, initial concentration and hydrophobicity of bile acid. The results showed that the sorption behavior of the modified CMFC was strongly influenced by the quaternary ammonium group content and the lengths of its alkyl substituent, the sorption capacity for the modified CMFC with a C18 alkyl substituent, was approximately 50% of that of Cholestyramine. The experimental isotherm results were well fitted into the Temkin model. The effect of salts in the solution was smaller for the bile acid sorption onto the hydrophobic CMFC than the CMFC. It was also found that the binding capacity of CMFC was higher for more hydrophobic deoxycholate in comparison with cholate. PMID- 26256388 TI - Tailoring chitosan/collagen scaffolds for tissue engineering: Effect of composition and different crosslinking agents on scaffold properties. AB - Chitosan/collagen (Chit/Col) blends have demonstrated great potential for use in tissue engineering (TE) applications. However, there exists a lack of detailed study on the influence of important design parameters (i.e, component ratio or crosslinking methods) on the essential properties of the scaffolds (morphology, mechanical stiffness, swelling, degradation and cytotoxicity). This work entailed a systematic study of these essential properties of three Chit/Col compositions, covering a wide range of component ratios and using different crosslinking methods. Our results showed the possibility of tailoring these properties by changing component ratios, since different interactions occurred between Chit/Col: samples with Chit-enriched compositions showed a hydrogen-bonding type complex (HC), whereas a self-crosslinking phenomenon was induced in Col-enriched scaffolds. Additionally, material and biological properties of the resultant matrices were further adjusted and tuned by changing crosslinking conditions. In such way, we obtained a wide range of scaffolds whose properties were tailored to meet specific needs of TE applications. PMID- 26256389 TI - Rheological properties and thickening mechanism of aqueous diutan gum solution: Effects of temperature and salts. AB - Rheological properties of a new microbial polysaccharide, diutan gum in aqueous solution have been systematically investigated. It is found that molecular aggregates of diutan gum can be formed at a very low concentration (0.12 g/L), and the mechanism of thickening by diutan gum is proposed. The viscosity retention rate of diutan gum changes little when increasing the temperature from 298 K to 348 K or in a high salinity solution (55.5 g L(-1)). Gel structure can be formed in the diutan gum solution, owing to the finding that the dynamic modulus has an exponential relationship with the concentration. The gel properties of diutan gum are not sensitive to temperature, and are virtually independent of cationic environment (Na(+) and Ca(2+)). The temperature/salt tolerance of the diutan gum solution is mainly attributed to its perfect double helix molecular conformation, the location of the side chains of its molecules, and its water retention capacity. PMID- 26256390 TI - Distribution of phosphorus and hydroxypropyl groups within granules of modified sweet potato starches as determined after chemical peeling. AB - The distributions of phosphorus and hydroxypropyl groups within granules of cross linked and hydroxypropylated sweet potato starches were investigated. Chemical surface peeling of starch granules was performed after sieving of native and modified starches into large-size (diameter >= 20 MUm) and small-size (diameter < 20 MUm) fractions. Starch granules were surface gelatinized in a 4M calcium chloride solution at different levels. After the peeling step, the remaining starch granules were analysed for the content of phosphorus and hydroxypropyl groups. The phosphorus level of the parental starch gradually decreased from periphery to core of the granules. The increase in phosphorus content after cross linking in periphery was higher than that in core. The subsequent hydroxypropylation reaction resulted in lower phosphate levels. Hydroxypropylation resulted in a gradient of hydroxypropyl group concentration from periphery to core. Cross-linking prior to the hydroxypropylation resulted in lower levels of hydroxypropyl groups and less pronounced differences between periphery and core. PMID- 26256391 TI - Protective effect of a polysaccharide from Salvia miltiorrhiza on isoproterenol (ISO)-induced myocardial injury in rats. AB - In this study, we investigated the cardioprotective effect of one purified polysaccharide (SMP1) from Salvia miltiorrhiza on isoproterenol (ISO)-induced myocardial infarction (MI) in rats. ISO-treated rats showed severe myocardial damage and high lipid peroxidation level, as well as decreased endogenous myocardial antioxidant function. Pretreatment with SMP1 (100 and 400mg/kg) for 30 days significantly increased the body weight, decreased the heart weight, attenuated the serum levels of creatine kinase (CK), creatine phospokinase-MB (CK MB), dehydrogenase (LDH), alkaline phosphate (ALP), aspartate transaminase (AST), alanine transaminase (ALT), total cholesterol, triglyceride, and LDL-cholesterol (LDL-C), along with the increased concentration of HDL-cholesterol (HDL-C). In addition, SMP1 also enhanced myocardial superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities and elevated myocardial reduced glutathione (GSH) level, along with a decrease in thiobarbituric acid reactive substances (TBARS) concentration. Collectively, our results indicated that long-term oral administration of SMP1 offered significant protection against the damage induced by ISO in rat heart through enhancement of endogenous antioxidants and antihyperlipidemic activity. PMID- 26256392 TI - Reversal of Mitochondrial Transhydrogenase Causes Oxidative Stress in Heart Failure. AB - Mitochondrial reactive oxygen species (ROS) play a central role in most aging related diseases. ROS are produced at the respiratory chain that demands NADH for electron transport and are eliminated by enzymes that require NADPH. The nicotinamide nucleotide transhydrogenase (Nnt) is considered a key antioxidative enzyme based on its ability to regenerate NADPH from NADH. Here, we show that pathological metabolic demand reverses the direction of the Nnt, consuming NADPH to support NADH and ATP production, but at the cost of NADPH-linked antioxidative capacity. In heart, reverse-mode Nnt is the dominant source for ROS during pressure overload. Due to a mutation of the Nnt gene, the inbred mouse strain C57BL/6J is protected from oxidative stress, heart failure, and death, making its use in cardiovascular research problematic. Targeting Nnt-mediated ROS with the tetrapeptide SS-31 rescued mortality in pressure overload-induced heart failure and could therefore have therapeutic potential in patients with this syndrome. PMID- 26256393 TI - The European Citizens' Stop Vivisection Initiative. PMID- 26256394 TI - The protozoan, Paramecium primaurelia, as a non-sentient model to test laser light irradiation: The effects of an 808nm infrared laser diode on cellular respiration. AB - Photobiomodulation (PBM) has been used in clinical practice for more than 40 years. Unfortunately, conflicting literature has led to the labelling of PBM as a complementary or alternative medicine approach. However, past and ongoing clinical and research studies by reputable investigators have re-established the merits of PBM as a genuine medical therapy, and the technique has, in the last decade, seen an exponential increase in the numbers of clinical instruments available, and their applications. This resurgence has led to a clear need for appropriate experimental models to test the burgeoning laser technology being developed for medical applications. In this context, an ethical model that employs the protozoan, Paramecium primaurelia, is proposed. We studied the possibility of using the measure of oxygen consumption to test PBM by irradiation with an infrared or near-infrared laser. The results show that an 808nm infrared laser diode (1W; 64J/cm2) affects cellular respiration in P. primaurelia, inducing, in the irradiated cells, a significantly (p < 0.05) increased oxygen consumption of about 40%. Our findings indicate that Paramecium can be an excellent tool in biological assays involving infrared and near-infrared PBM, as it combines the advantages of in vivo results with the practicality of in vitro testing. This test represents a fast, inexpensive and straightforward assay, which offers an alternative to both traditional in vivo testing and more expensive mammalian cellular cultures. PMID- 26256395 TI - The Ex Vivo Eye Irritation Test as an alternative test method for serious eye damage/eye irritation. AB - Ocular irritation testing is a common requirement for the classification, labelling and packaging of chemicals (substances and mixtures). The in vivo Draize rabbit eye test (OECD Test Guideline 405) is considered to be the regulatory reference method for the classification of chemicals according to their potential to induce eye injury. In the Draize test, chemicals are applied to rabbit eyes in vivo, and changes are monitored over time. If no damage is observed, the chemical is not categorised. Otherwise, the classification depends on the severity and reversibility of the damage. Alternative test methods have to be designed to match the classifications from the in vivo reference method. However, observation of damage reversibility is usually not possible in vitro. Within the present study, a new organotypic method based on rabbit corneas obtained from food production is demonstrated to close this gap. The Ex Vivo Eye Irritation Test (EVEIT) retains the full biochemical activity of the corneal epithelium, epithelial stem cells and endothelium. This permits the in-depth analysis of ocular chemical trauma beyond that achievable by using established in vitro methods. In particular, the EVEIT is the first test to permit the direct monitoring of recovery of all corneal layers after damage. To develop a prediction model for the EVEIT that is comparable to the GHS system, 37 reference chemicals were analysed. The experimental data were used to derive a three-level potency ranking of eye irritation and corrosion that best fits the GHS categorisation. In vivo data available in the literature were used for comparison. When compared with GHS classification predictions, the overall accuracy of the three-level potency ranking was 78%. The classification of chemicals as irritating versus non-irritating resulted in 96% sensitivity, 91% specificity and 95% accuracy. PMID- 26256396 TI - The EpiOcularTM Eye Irritation Test is the Method of Choice for the In Vitro Eye Irritation Testing of Agrochemical Formulations: Correlation Analysis of EpiOcular Eye Irritation Test and BCOP Test Data According to the UN GHS, US EPA and Brazil ANVISA Classification Schemes. AB - The Bovine Corneal Opacity and Permeability (BCOP) test is commonly used for the identification of severe ocular irritants (GHS Category 1), but it is not recommended for the identification of ocular irritants (GHS Category 2). The incorporation of human reconstructed tissue model-based tests into a tiered test strategy to identify ocular non-irritants and replace the Draize rabbit eye irritation test has been suggested (OECD TG 405). The value of the EpiOcularTM Eye Irritation Test (EIT) for the prediction of ocular non-irritants (GHS No Category) has been demonstrated, and an OECD Test Guideline (TG) was drafted in 2014. The purpose of this study was to evaluate whether the BCOP test, in conjunction with corneal histopathology (as suggested for the evaluation of the depth of the injury( and/or the EpiOcular-EIT, could be used to predict the eye irritation potential of agrochemical formulations according to the UN GHS, US EPA and Brazil ANVISA classification schemes. We have assessed opacity, permeability and histopathology in the BCOP assay, and relative tissue viability in the EpiOcular-EIT, for 97 agrochemical formulations with available in vivo eye irritation data. By using the OECD TG 437 protocol for liquids, the BCOP test did not result in sufficient correct predictions of severe ocular irritants for any of the three classification schemes. The lack of sensitivity could be improved somewhat by the inclusion of corneal histopathology, but the relative viability in the EpiOcular-EIT clearly outperformed the BCOP test for all three classification schemes. The predictive capacity of the EpiOcular-EIT for ocular non-irritants (UN GHS No Category) for the 97 agrochemical formulations tested (91% sensitivity, 72% specificity and 82% accuracy for UN GHS classification) was comparable to that obtained in the formal validation exercise underlying the OECD draft TG. We therefore conclude that the EpiOcular-EIT is currently the best in vitro method for the prediction of the eye irritation potential of liquid agrochemical formulations. PMID- 26256397 TI - Non-animal Replacements for Acute Toxicity Testing. AB - Current approaches to predicting adverse effects in humans from acute toxic exposure to cosmetic ingredients still heavily necessitate the use of animals under EU legislation, particularly in the context of the REACH system, when cosmetic ingredients are also destined for use in other industries. These include the LD50 test, the Up-and-Down Procedure and the Fixed Dose Procedure, which are regarded as having notable scientific deficiencies and low transferability to humans. By expanding on previous in vitro tests, such as the animal cell-based 3T3 Neutral Red Uptake (NRU) assay, this project aims to develop a truly animal free predictive test for the acute toxicity of cosmetic ingredients in humans, by using human-derived cells and a prediction model that does not rely on animal data. The project, funded by Innovate UK, will incorporate the NRU assay with human dermal fibroblasts in animal product-free culture, to generate an in vitro protocol that can be validated as an accepted replacement for the currently available in vivo tests. To date, the project has successfully completed an assessment of the robustness and reproducibility of the method, by using sodium lauryl sulphate (SLS) as a positive control, and displaying analogous results to those of the original studies with mouse 3T3 cells. Currently, the testing of five known ingredients from key groups (a surfactant, a preservative, a fragrance, a colour and an emulsifier) is under way. The testing consists of initial range-finding runs followed by three valid runs of a main experiment with the appropriate concentration ranges, to generate IC50 values. Expanded blind trials of 20 ingredients will follow. Early results indicate that this human cell based test holds the potential to replace aspects of in vivo animal acute toxicity testing, particularly with reference to cosmetic ingredients. PMID- 26256398 TI - Single Housing of Primates in US Laboratories: A Growing Problem with Shrinking Transparency. PMID- 26256399 TI - In Vitro Models to Mimic the Endothelial Barrier. PMID- 26256400 TI - 17. The Choice of Procedures. PMID- 26256401 TI - Wavelet formulation of the polarizable continuum model. II. Use of piecewise bilinear boundary elements. AB - The simplicity of dielectric continuum models has made them a standard tool in almost any Quantum Chemistry (QC) package. Despite being intuitive from a physical point of view, the actual electrostatic problem at the cavity boundary is challenging: the underlying boundary integral equations depend on singular, long-range operators. The parametrization of the cavity boundary should be molecular-shaped, smooth and differentiable. Even the most advanced implementations, based on the integral equation formulation (IEF) of the polarizable continuum model (PCM), generally lead to working equations which do not guarantee convergence to the exact solution and/or might become numerically unstable in the limit of large refinement of the molecular cavity (small tesserae). This is because they generally make use of a surface parametrization with cusps (interlocking spheres) and employ collocation methods for the discretization (point charges). Wavelets on a smooth cavity are an attractive alternative to consider: for the operators involved, they lead to highly sparse matrices and precise error control. Moreover, by making use of a bilinear basis for the representation of operators and functions on the cavity boundary, all equations can be differentiated to enable the computation of geometrical derivatives. In this contribution, we present our implementation of the IEFPCM with bilinear wavelets on a smooth cavity boundary. The implementation has been carried out in our module PCMSolver and interfaced with LSDalton, demonstrating the accuracy of the method both for the electrostatic solvation energy and for linear response properties. In addition, the implementation in a module makes our framework readily available to any QC software with minimal effort. PMID- 26256402 TI - Stigma, discrimination and HIV outcomes among people living with HIV in Rio de Janeiro, Brazil: The intersection of multiple social inequalities. AB - Limited research has examined the social context surrounding stigma and discrimination and HIV outcomes among people living with HIV (PLHIV). We surveyed 900 PLHIV in Brazil and examined the relationship between stigma, discrimination and HIV outcomes utilising multivariable logistic regression. HIV stigma and discrimination were inversely associated with age (AOR Stigma 0.65, 95% CI 0.49 0.88; AOR Discrimination 0.72, 95% CI 0.54-0.95) and income (AOR Stigma 0.74, 95% CI 0.55-0.99; AOR Discrimination 0.62, 95% CI 0.46-0.82). Stigma was inversely associated with education (AOR 0.71, 95% CI 0.52-0.96) and no history of sex work (AOR 0.56, 95% CI 0.35-0.90), and positively associated with having children (AOR 1.71, 95% CI 1.18-2.48). Discrimination was inversely associated with no history of drug use (AOR 0.63, 95% CI 0.42-0.95). Stigma and discrimination were found to be inversely associated with overall health (AOR Stigma 0.54, 95% CI 0.40-0.74; AOR Discrimination 0.71, 95% CI 0.52-0.97). Discrimination was associated with having a sexually transmitted infection since HIV diagnosis (AOR 1.63, 95% CI 1.14-2.32). Findings suggest that future interventions should address multiple social inequalities faced by PLHIV to reduce HIV stigma and discrimination and improve health and HIV outcomes. PMID- 26256403 TI - Discovery and structural optimization of 1-phenyl-3-(1-phenylethyl)urea derivatives as novel inhibitors of CRAC channel. AB - AIM: Ca(2+)-release-activated Ca(2+) (CRAC) channel, a subfamily of store operated channels, is formed by calcium release-activated calcium modulator 1 (ORAI1), and gated by stromal interaction molecule 1 (STIM1). CRAC channel may be a novel target for the treatment of immune disorders and allergy. The aim of this study was to identify novel small molecule CRAC channel inhibitors. METHODS: HEK293 cells stably co-expressing both ORAI1 and STIM1 were used for high throughput screening. A hit, 1-phenyl-3-(1-phenylethyl)urea, was identified that inhibited CRAC channels by targeting ORAI1. Five series of its derivatives were designed and synthesized, and their primary structure-activity relationships (SARs) were analyzed. All derivatives were assessed for their effects on Ca(2+) influx through CRAC channels on HEK293 cells, cytotoxicity in Jurkat cells, and IL-2 production in Jurkat cells expressing ORAI1-SS-eGFP. RESULTS: A total of 19 hits were discovered in libraries containing 32 000 compounds using the high throughput screening. 1-Phenyl-3-(1-phenylethyl)urea inhibited Ca(2+) influx with IC50 of 3.25+/-0.17 MUmol/L. SAR study on its derivatives showed that the alkyl substituent on the alpha-position of the left-side benzylic amine (R1) was essential for Ca(2+) influx inhibition and that the S-configuration was better than the R-configuration. The derivatives in which the right-side R3 was substituted by an electron-donating group showed more potent inhibitory activity than those that were substituted by electron-withdrawing groups. Furthermore, the free N-H of urea was not necessary to maintain the high potency of Ca(2+) influx inhibition. The N,N'-disubstituted or N'-substituted derivatives showed relatively low cytotoxicity but maintained the ability to inhibit IL-2 production. Among them, compound 5b showed an improved inhibition of IL-2 production and low cytotoxicity. CONCLUSION: 1-Phenyl-3-(1-phenylethyl)urea is a novel CRAC channel inhibitor that specifically targets ORAI1. This study provides a new chemical scaffold for design and development of CRAC channel inhibitors with improved Ca(2+) influx inhibition, immune inhibition and low cytotoxicity. PMID- 26256404 TI - Enhancement of cellular uptake, transport and oral absorption of protease inhibitor saquinavir by nanocrystal formulation. AB - AIM: Saquinavir (SQV) is the first protease inhibitor for the treatment of HIV infection, but with poor solubility. The aim of this study was to prepare a colloidal nanocrystal suspension for improving the oral absorption of SQV. METHODS: SQV nanocrystals were prepared using anti-solvent precipitation-high pressure homogenization method. The nanocrystals were characterized by a Zetasizer and transmission electron microscopy (TEM). Their dissolution, cellular uptake and transport across the human colorectal adenocarcinoma cell line (Caco 2) monolayer were investigated. Bioimaging of ex vivo intestinal sections of rats was conducted with confocal laser scanning microscopy. Pharmacokinetic analysis was performed in rats administered nanocrystal SQV suspension (50 mg/kg, ig), and the plasma SQV concentrations were measured with HPLC. RESULTS: The SQV nanocrystals were approximately 200 nm in diameter, with a uniform size distribution. The nanocrystals had a rod-like shape under TEM. The dissolution, cellular uptake, and transport across a Caco-2 monolayer of the nanocrystal formulation were significantly improved compared to those of the coarse crystals. The ex vivo intestinal section study revealed that the fluorescently labeled nanocrystals were located in the lamina propria and the epithelium of the duodenum and jejunum. Pharmacokinetic study showed that the maximal plasma concentration (Cmax) was 2.16-fold of that for coarse crystalline SQV suspension, whereas the area under the curve (AUC) of nanocrystal SQV suspension was 1.95 fold of that for coarse crystalline SQV suspension. CONCLUSION: The nanocrystal drug delivery system significantly improves the oral absorption of saquinavir. PMID- 26256405 TI - Cardiorespiratory and anesthetic effects produced by the combination of butorphanol, medetomidine and alfaxalone administered intramuscularly in Beagle dogs. AB - This study evaluated anesthesia quality, degree of analgesia and cardiorespiratory parameters after intramuscular (IM) injection of a combination of butorphanol (0.1 mg/kg), medetomidine (10 ug/kg) and alfaxalone (1.5 mg/kg) in ten healthy adult Beagle dogs. Rectal temperature (T), heart rate (HR), respiratory rate (fR), arterial pressure, arterial blood gases and M-mode echocardiographic left ventricular (LV) indices were measured before drug administration and every 10 min thereafter until extubation. Mean duration of anesthesia, recovery and analgesia were 89 +/- 17, 6 +/- 1 and 80 +/- 12 min. HR, fR, partial pressure of arterial CO2 and O2, arterial pressure, and LV contractility were significantly altered during anesthesia. IM administration of the drug combination provided acceptable anesthesia, but produced substantial cardiorespiratory suppression. PMID- 26256406 TI - Cardiac ganglioneuroma in a juvenile pig. AB - A cardiac mass (3 * 5 * 3 cm) was detected at the base between the right auricular wall and right vena cava of a slaughtered 6-month-old female mixed breed pig during a meat inspection. The tumor comprised infiltrative prominent interweaving fascicles of Schwann cells with Verocay bodies. Moreover, the ganglion cells were scattered or aggregated throughout the neoplastic tissue. The ganglion and Schwann cells had neither cellular atypism nor mitosis. On the basis of the bearing site as well as the morphological and immunohistochemical features, this is the first case of a cardiac ganglioneuroma in a pig. PMID- 26256407 TI - Electronic and Chemical Properties of Donor, Acceptor Centers in Graphene. AB - Chemical doping is one of the most suitable ways of tuning the electronic properties of graphene and a promising candidate for a band gap opening. In this work we report a reliable and tunable method for preparation of high-quality boron and nitrogen co-doped graphene on silicon carbide substrate. We combine experimental (dAFM, STM, XPS, NEXAFS) and theoretical (total energy DFT and simulated STM) studies to analyze the structural, chemical, and electronic properties of the single-atom substitutional dopants in graphene. We show that chemical identification of boron and nitrogen substitutional defects can be achieved in the STM channel due to the quantum interference effect, arising due to the specific electronic structure of nitrogen dopant sites. Chemical reactivity of single boron and nitrogen dopants is analyzed using force-distance spectroscopy by means of dAFM. PMID- 26256408 TI - 17beta-Estradiol in the systemic circulation derives mainly from the parietal cells in cholestatic female rats. AB - PURPOSE: Estrogenic symptoms of liver disease patients including biliary tract disorder with high frequency is observed in clinical cases. However, the origin of 17beta-estradiol which is abundant enough to cause symptoms remains uncertain. In male rats, it has been reported that the parietal cells which have an abundance of aromatase-synthesized 17beta-estradiol, and a part of 17beta estradiol secreted into the portal vein, may flow into the systemic circulation under a pathophysiological condition of the liver including bile duct ligation (BDL). The aim of this study is to reveal the origin of 17beta-estradiol increment in female rats and to investigate the effect of BDL on the ovary during the estrus cycle. METHODS: Wistar female rats were used, and the common bile duct was ligated twice and transected completely at 7 days before termination. Serum portal venous and arterial 17beta-estradiol levels, Cyp19a1 expressions, aromatase protein levels, and estrogen receptor (ER) alpha levels in the liver were measured during the estrus cycle. RESULTS: Both arterial and portal venous 17beta-estradiol levels increased 2.9 times at proestrus and maintained constant levels during the cycle. The expression of Cyp19a1 and aromatase protein in the stomach maintained constant levels, and significantly decreased during the estrus cycle in the ovary. Hepatic ERalpha protein and Esr1 expressions decrease by BDL in all stages. CONCLUSIONS: These results suggest that the increment of serum 17beta-estradiol levels in obstructive cholestasis induced by BDL is derived from 17beta-estradiol secreted from the parietal cells in females as well as males. PMID- 26256409 TI - Formation of Cucurbit[8]uril-Based Supramolecular Hydrogel Beads Using Droplet Based Microfluidics. AB - Herein we describe the use of microdroplets as templates for the fabrication of uniform-sized supramolecular hydrogel beads, assembled by supramolecular cross linking of functional biopolymers with the macrocyclic host molecule, cucurbit[8]uril (CB[8]). The microdroplets were formed containing diluted hydrogel precursors in solution, including the functional polymers and CB[8], in a microfluidic device. Subsequent evaporation of water from collected microdroplets concentrated the contents, driving the formation of the CB[8] mediated host-guest ternary complex interactions and leading to the assembly of condensed three-dimensional polymeric scaffolds. Rehydration of the dried particles gave monodisperse hydrogel beads. Their equilibrium size was shown to be dependent on both the quantity of material loaded and the dimensions of the microfluidic flow focus. Fluorescein-labeled dextran was used to evaluate the efficacy of the hydrogel beads as a vector for controlled cargo release. Both passive, sustained release (hours) and triggered, fast release (minutes) of the FITC-dextran was observed, with the rate of sustained release dependent on the formulation. The kinetics of release was fitted to the Ritger-Peppas controlled release equation and shown to follow an anomalous (non-Fickian) transport mechanism. PMID- 26256410 TI - Elusive 2H-1,2-oxasiletes through reactions of an isolable dialkylsilylene with diazocarbonyl compounds. AB - The reactions of isolable dialkysilylene 1 with 2-diazo-1,2-diphenylethanone and ethyl 2-diazo-2-phenylacetate gave elusive silacycles, 2H-1,2-oxasiletes 2 and 3, respectively, in high yields. Because these reactions occur at low temperatures of ca.-30 degrees C, initial complexation of the silylene to the carbonyl oxygen of the diazocarbonyl compounds is suggested to trigger dinitrogen elimination followed by cyclization. In contrast, a six-membered cyclic diazo compound 8 and 1-sila-2,3-diazabicyclo[3.3.0]oct-3-ene 10 were obtained in good yields by the reaction of 1 with less reactive ethyl 2-diazo-3-oxo-3-phenylpropanoate 7 and trimethylsilyldiazomethane 9. Molecular structures of 2, 3, 8 and 10 were determined by X-ray crystallography. PMID- 26256411 TI - 'The patient': at the center of patient-reported outcomes. AB - The recent emphasis of including patient reports in their own care management is reviewed in terms of the factors that contributed to its popularity. The role change of patients as being active participants in their own care as a result of the rising consumerism and advocacy has led to increased pressures for including patients in the therapeutic decision-making process. As consumers of clinical services, their perspectives and attitudes towards health and illness acquired more importance. The rising cost of healthcare has added another dimension in cost containment by empowering patients and sharing responsibility in their recovery, which hopefully can improve outcomes. Challenges in the development and implementation of patient-reported outcomes in psychiatry are reviewed and include the still unresolved subjective/objective dichotomy, identification of the most appropriate and relevant patient-reported outcomes. Few outcomes are identified and include: subjective tolerability of medication, self-reported health-related quality of life, preferences, patients' attitudes towards health and illness, satisfaction with medication and overall satisfaction of quality of care, and functional state, with particular focus on social functioning. PMID- 26256412 TI - The cost-effectiveness of novel direct acting antiviral agent therapies for the treatment of chronic hepatitis C. AB - In the USA, over 3 million individuals are infected with the HCV and 75-85% of them have or will develop chronic hepatitis C (CHC) which can lead to serious consequences such as liver cirrhosis, cancer and death. The old standard of care for the treatment of CHC was Pegylated-Interferon + Ribavirin with or without a protease inhibitor such as Boceprevir/Telaprevir. These treatments had a cure rate or rate of sustained virologic response of 66-80%. Since the close of 2013, several new direct acting antiviral agents (DAAs) for the treatment of CHC have been approved by the US FDA and have entered the US drug market. These novel CHC treatments boast very high cure rates of 80-100% and come with matching high price tags. Costs of CHC regimens that contain these novel DAAs range from $63,000 to $168,000 per treatment course. Using electronic databases, studies evaluating the cost-effectiveness of novel CHC treatments in USA were reviewed, and the reported incremental cost-effectiveness ratios based on cost per additional quality adjusted life year gained from the studies reviewed indicated that some novel DAA regimens are cost-effective; however, cost-effectiveness is contingent upon a variety of factors such as HCV genotype (1-4), presence of liver cirrhosis, patient treatment history and willingness-to-pay thresholds. PMID- 26256414 TI - Greater serum carotenoid levels associated with lower prevalence of nonalcoholic fatty liver disease in Chinese adults. AB - Previous studies have suggested that serum carotenoids may be inversely associated with liver injury, but limited data are available from population based studies. We examined the relationship between serum carotenoid levels and the prevalence of nonalcoholic fatty liver disease (NAFLD) in Chinese adults. A total of 2935 participants aged 40-75 years were involved in this community-based cross-sectional study. General information, lifestyle factors, serum levels of carotenoid and the presence and degree of NAFLD were determined. After adjusting for potential covariates, we observed a dose-dependent inverse association between NAFLD risk and each individual serum carotenoid and total carotenoids (all p-values < 0.001). The ORs of NAFLD for the highest (vs. lowest) quartile were 0.44 (95% CI 0.35, 0.56) for alpha-carotene, 0.32 (95% CI 0.25, 0.41) for beta-carotene, 0.62 (95% CI 0.49, 0.79) for beta-cryptoxanthin, 0.54 (95% CI 0.42, 0.68) for lycopene, 0.56 (95% CI 0.44, 0.72) for lutein + zeaxanthin and 0.41 (95% CI 0.32, 0.53) for total carotenoids. Higher levels of alpha-carotene, beta-carotene, lutein + zeaxanthin and total carotenoids were significantly associated with a decrease in the degree of NAFLD (p-trend: < 0.001 to 0.003). Serum carotenoids are inversely associated with prevalence of NAFLD in middle aged and elderly Chinese. PMID- 26256415 TI - Self-propelled worm-like filaments: spontaneous spiral formation, structure, and dynamics. AB - Worm-like filaments that are propelled homogeneously along their tangent vector are studied by Brownian dynamics simulations. Systems in two dimensions are investigated, corresponding to filaments adsorbed to interfaces or surfaces. A large parameter space covering weak and strong propulsion, as well as flexible and stiff filaments is explored. For strongly propelled and flexible filaments, the free-swimming filaments spontaneously form stable spirals. The propulsion force has a strong impact on dynamic properties, such as the rotational and translational mean square displacement and the rate of conformational sampling. In particular, when the active self-propulsion dominates thermal diffusion, but is too weak for spiral formation, the rotational diffusion coefficient has an activity-induced contribution given by v(c)/xi(P), where v(c) is the contour velocity and xi(P) the persistence length. In contrast, structural properties are hardly affected by the activity of the system, as long as no spirals form. The model mimics common features of biological systems, such as microtubules and actin filaments on motility assays or slender bacteria, and artificially designed microswimmers. PMID- 26256416 TI - Mas receptor overexpression increased Ang-(1-7) relaxation response in renovascular hypertensive rat carotid. AB - Renin-angiotensin system (RAS) is an important factor in the pathophysiology of hypertension. Mas receptor, Angiotensin-(1-7) [Ang-(1-7)]-activated receptor, is an important RAS component and exerts protective effects in the vasculature. Ang (1-7) vascular effects and Mas receptor expression in carotid from renovascular hypertensive (2K-1C) rats is not clear. In the present study we investigated Mas receptor vasodilator response activated by Ang-(1-7) in the carotid rings from sham and 2K-1C rats. Changes in isometric tension were recorded on organ chamber. Mas receptors expression was investigated in carotid by Western blot. Nitric oxide production was evaluated by 2,3-diaminonaphthalene (DAN) and eNOS expression and activity by immunofluoresce and western blot, respectively. Ang-(1 7) induced concentration-dependent vasodilator effect in carotid rings from sham and 2K-1C, which the hypertension increased vasodilatation response. In the 2K-1C carotid rings, A-779 (Mas receptor antagonist) reduced but not abolish the vasodilator effect of Ang-(1-7). Corroborating, Mas receptor protein expression was significantly increased in the 2K-1C rats. L-NAME and ibuprofen decreased Ang (1-7) vasodilator response and L-NAME plus ibuprofen practically abolish the remaining vasodilatation response. Nitric oxide production is increased due increased of eNOS expression and pSer(1177) activity. Our results demonstrated that renovascular hypertension increased Mas receptors expression and nitric oxide production in the rats carotid which, consequently increased Ang-(1-7) vasorelaxant response. PMID- 26256417 TI - Pyrosequencing for rapid detection of Mycobacterium tuberculosis second-line drugs and ethambutol resistance. AB - The aim of this work was to study the diagnostic accuracy of pyrosequencing to detect resistance to fluoroquinolones, kanamycin, amikacin, capreomycin, and ethambutol (EMB) in Mycobacterium tuberculosis clinical strains. One hundred four clinical isolates previously characterized by BACTEC 460TB/MGIT 960 were included. Specific mutations were targeted in gyrA, rrs, eis promoter, and embB. When there was a discordant result between BACTEC and pyrosequencing, Genotype MTBDRsl (Hain Lifescience, Nehren, Germany) was performed. Sensitivity and specificity of pyrosequencing were 70.6% and 100%, respectively, for fluoroquinolones; 93.3% and 81.7%, respectively, for kanamycin; 94.1% and 95.9%, respectively, for amikacin; 90.0% and 100%, respectively, for capreomycin; and 64.8% and 87.8%, respectively, for EMB. This study shows that pyrosequencing may be a useful tool for making early decisions regarding second-line drugs and EMB resistance. However, for a correct management of patients with suspected extensively drug-resistant tuberculosis, susceptibility results obtained by molecular methods should be confirmed by a phenotypic method. PMID- 26256418 TI - Early detection with the beta-LACTATM test of extended-spectrum beta-lactamase producing Enterobacteriaceae in blood cultures. AB - Effective antibiotic therapy is crucial for the outcome of septic patients and requires early diagnosis of beta-lactam resistance in cases of Gram-negative bacteremia. Here, we report high sensitivity of the beta-LACTATM test in rapid detection of extended-spectrum beta-lactamase-producing Enterobacteriaceae in blood cultures positive for Gram-negative bacilli. PMID- 26256419 TI - How is the Xpert MRSA Gen 3 assay (Cepheid) performing on pooled eSwab medium? AB - The performance of the Xpert MRSA Gen 3 was compared to the Xpert MRSA on pooled eSwab media from nose, throat, and perineum using broth enriched cultured as gold standard. A lower specificity was found for the Xpert MRSA Gen 3 compared to the Xpert MRSA (91.8% versus 97.9%; P<0.05). PMID- 26256420 TI - Phosphodiesterase 10A inhibitor, MP-10 (PF-2545920), produces greater induction of c-Fos in dopamine D2 neurons than in D1 neurons in the neostriatum. AB - Studies described here tested the hypothesis that phosphodiesterase 10A inhibition by a selective antagonist, MP-10, activates the dopamine D2 receptor expressing medium spiny neurons to a greater extent than the D1 receptor expressing neurons. We used regional pattern of c-Fos induction in the neostriatal subregions of rodents and direct assessment of D1-positive and negative neurons in the DRd1a-tdTomato mice for the purpose. MP-10 (1, 3, 10 or 30 mg/kg, PO) dose-dependently increased c-Fos immunopositive nuclei in all regions of neostriatum. However, the effect was statistically greater in the dorsolateral striatum, a region known to be activated preferentially by the D2 antagonism, than the D1-activated dorsomedial striatum. The D2 antagonist, haloperidol (0.3, 1, or 3 mg/kg, PO) produced an identical, regional pattern of c Fos induction favoring the dorsolateral striatum of the rat. In contrast, the D1 agonist, SKF82958 (0.5, 1, or 2 mg/kg, PO), induced greater expression of c-Fos in the dorsomedial striatum. The C57Bl/6 mouse also showed regionally preferential c-Fos activation by haloperidol (2 mg/kg, IP) and SKF82858 (3 mg/kg, IP). In the Drd1a-tdTomato mice, MP-10 (3 or 10 mg/kg, IP) increased c-Fos immunoreactivity in both types of neurons, the induction was greater in the D1 negative neurons. Taken together, both the regional pattern of c-Fos induction in the striatal sub-regions and the greater induction of c-Fos in the D1-negative neurons indicate that PDE10A inhibition produces a small but significantly greater activation of the D2-containing striatopallidal pathway. PMID- 26256421 TI - The protective effects and underlying mechanism of an anti-oligomeric Abeta42 single-chain variable fragment antibody. AB - Oligomeric Abeta42 aggregates have been identified as one of the major neurotoxic components of Alzheimer's disease (AD). Immunotherapy targeted against these Abeta42 aggregates has been proposed as an appropriate therapeutic approach for the treatment of AD. Here, we report an anti-oligomeric Abeta42 single-chain variable fragment (scFv) antibody, named MO6, obtained from the human antibody library of a healthy donor. ScFv MO6 specifically recognized and bound to the oligomeric Abeta42 (Abeta42 oligomers and immature protofibrils; 18-37 kDa), and reduced their levels mainly by blocking their formation, although scFv MO6 also induced disaggregation of Abeta42 aggregates. More importantly, scFv MO6 ameliorated or attenuated Abeta42-induced cytotoxicity and increased cell viability by up to 33%. Furthermore, scFv MO6 efficiently passed through an in vitro blood-brain barrier (BBB) model with a delivery efficiency of 66% after 60 min post-administration. ScFv MO6 is a monovalent antibody with an affinity constant (KD) of 5.2*10(-6) M for Abeta42 oligomers. Molecular docking simulations of Abeta42 to scFv MO6 revealed that the approach and specific binding of scFv MO6 to oligomeric Abeta42 aggregates was achieved by conformational recognition and directed induction, which resulted in a more dynamic adaptation of Abeta42 to scFv MO6, occurring mainly in the N-terminal (3 4), middle (12-19) and C-terminal (34-42) regions of Abeta42. This binding mode of scFv MO6 to Abeta42 explains its protective effects against oligomeric Abeta42. Our findings may be applied for the design of a smaller antibody specific for Abeta42 oligermers. PMID- 26256423 TI - Purinergic neurone-glia signalling in cognitive-related pathologies. AB - Neuroglia, represented by astrocytes, oligodendrocytes, NG glia and microglia are homeostatic, myelinating and defensive cells of the brain. Neuroglial cells express various combinations of purinoceptors, which contribute to multiple intercellular signalling pathways in the healthy and diseased nervous system. Neurological diseases are invariably associated with profound neuroglial remodelling, which is manifest by reactive gliosis, pathological remodelling and functional atrophy of various types of glial cells. Gliopathology is disease and region specific and produces multiple glial phenotypes that may be neuroprotective or neurotoxic. In this review we summarise recent knowledge on the role of glial purinergic signalling in cognitive-related neurological diseases. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'. PMID- 26256422 TI - Ketogenic diet prevents epileptogenesis and disease progression in adult mice and rats. AB - Epilepsy is a highly prevalent seizure disorder which tends to progress in severity and become refractory to treatment. Yet no therapy is proven to halt disease progression or to prevent the development of epilepsy. Because a high fat low carbohydrate ketogenic diet (KD) augments adenosine signaling in the brain and because adenosine not only suppresses seizures but also affects epileptogenesis, we hypothesized that a ketogenic diet might prevent epileptogenesis through similar mechanisms. Here, we tested this hypothesis in two independent rodent models of epileptogenesis. Using a pentylenetetrazole kindling paradigm in mice, we first show that a KD, but not a conventional antiepileptic drug (valproic acid), suppressed kindling-epileptogenesis. Importantly, after treatment reversal, increased seizure thresholds were maintained in those animals kindled in the presence of a KD, but not in those kindled in the presence of valproic acid. Next, we tested whether a KD can halt disease progression in a clinically relevant model of progressive epilepsy. Epileptic rats that developed spontaneous recurrent seizures after a pilocarpine induced status epilepticus were treated with a KD or control diet (CD). Whereas seizures progressed in severity and frequency in the CD-fed animals, KD-fed animals showed a prolonged reduction of seizures, which persisted after diet reversal. KD-treatment was associated with increased adenosine and decreased DNA methylation, the latter being maintained after diet discontinuation. Our findings demonstrate that a KD prevented disease progression in two mechanistically different models of epilepsy, and suggest an epigenetic mechanism underlying the therapeutic effects. PMID- 26256424 TI - Novel phenanthroline-diaryldiazadiene ligands with heteroditopic coordination spheres. AB - 1,10-Phenanthroline-5,6-diaryldiazadienes are key structures for the development of novel heterodinuclear photocatalysts and for the construction of extended heterocycles of potential biological use. Herein, the first examples of this compound family are presented together with a wide range of initial reactivity studies. Synthetic strategies are presented to access the two first derivatives of the ligand and to accomplish subsequent metal coordination to the phenanthroline sphere. PMID- 26256425 TI - The secreted fructose 1,6-bisphosphate aldolase as a broad spectrum vaccine candidate against pathogenic bacteria in aquaculture. AB - The development of aquaculture has been hampered by different aquatic pathogens that can cause edwardsiellosis, vibriosis, or other diseases. Therefore, developing a broad spectrum vaccine against different fish diseases is necessary. In this study, fructose 1,6-bisphosphate aldolase (FBA), a conserved enzyme in the glycolytic pathway, was demonstrated to be located in the non-cytoplasmic components of five aquatic pathogenic bacteria and exhibited remarkable protection and cross-protection against these pathogens in turbot and zebrafish. Further analysis revealed that sera sampled from vaccinated turbot had a high level of specific antibody and bactericidal activity against these pathogens. Meanwhile, the increased expressions of immune response-related genes associated with antigen recognition and presentation indicated that the adaptive immune response was effectively aroused. Taken together, our results suggest that FBA can be utilized as a broad-spectrum vaccine against various pathogenic bacteria of aquaculture in the future. PMID- 26256426 TI - Raman micro-spectroscopy study of living SH-SY5Y cells adhering on different substrates. AB - In this paper we test the ability of Raman micro-spectroscopy and Raman mapping to investigate the status of cells grown in adhesion on different substrates. The spectra of immortalized SH-SY5Y cells, grown on silicon and on metallic substrates are compared with those obtained for the same type of cells adhering on organic polyaniline (PANI), a memristive substrate chosen to achieve a living bio-hybrid system. Raman spectra give information on the status of the single cell, its local biochemical composition, and on the modifications induced by the substrate interaction. The good agreement between Raman spectra collected from cells adhering on different substrates confirms that the PANI, besides allowing the cell growth, doesn't strongly affect the general biochemical properties of the cell. The investigation of the cellular state in a label free condition is challenging and the obtained results confirm the Raman ability to achieve this information. PMID- 26256427 TI - Different roles of the medial and lateral hamstrings in unloading the anterior cruciate ligament. AB - INTRODUCTION: Anterior cruciate ligament injuries are closely associated with excessive loading and motion about the off axes of the knee, i.e. tibial rotation and knee varus/valgus. However, it is not clear about the 3-D mechanical actions of the lateral and medial hamstring muscles and their differences in loading the ACL. The purpose of this study was to investigate the change in anterior cruciate ligament strain induced by loading the lateral and medial hamstrings individually. METHODS: Seven cadaveric knees were investigated using a custom testing apparatus allowing for six degree-of-freedom tibiofemoral motion induced by individual muscle loading. With major muscles crossing the knee loaded moderately, the medial and lateral hamstrings were loaded independently to 200N along their lines of actions at 0 degrees , 30 degrees , 60 degrees and 90 degrees of knee flexion. The induced strain of the anterior cruciate ligament was measured using a differential variable reluctance transducer. Tibiofemoral kinematics was monitored using a six degrees-of-freedom knee goniometer. RESULTS: Loading the lateral hamstrings induced significantly more anterior cruciate ligament strain reduction (mean 0.764 [SD 0.63] %) than loading the medial hamstrings (mean 0.007 [0.2] %), (P=0.001 and effect size=0.837) across the knee flexion angles. CONCLUSION: The lateral and medial hamstrings have significantly different effects on anterior cruciate ligament loadings. More effective rehabilitation and training strategies may be developed to strengthen the lateral and medial hamstrings selectively and differentially to reduce anterior cruciate ligament injury and improve post-injury rehabilitation. CLINICAL RELEVANCE: The lateral and medial hamstrings can potentially be strengthened selectively and differentially as a more focused rehabilitation approach to reduce ACL injury and improve post-injury rehabilitation. Different ACL reconstruction procedures with some of them involving the medial hamstrings can be compared to each other for their effect on ACL loading. PMID- 26256428 TI - Rosacea is associated with chronic systemic diseases in a skin severity-dependent manner: results of a case-control study. AB - BACKGROUND: Rosacea is a common chronic inflammatory dermatosis of unclear origin. It has been associated with systemic comorbidities, but methodical studies addressing this association are lacking. OBJECTIVE: We evaluated: (1) the association between rosacea and systemic comorbidities; and (2) if the severity of rosacea is impacted by comorbidities. METHODS: This was a case-control study: patients with rosacea were matched (1:1) to rosacea-free control subjects by age, sex, and race. Relative risk estimates were calculated using logistic regression as odds ratios with 95% confidence intervals. RESULTS: Among 130 participants (65 patients/65 control subjects), we observed a significant association between rosacea and allergies (airborne, food), respiratory diseases, gastroesophageal reflux disease, other gastrointestinal diseases, hypertension, metabolic and urogenital diseases, and female hormone imbalance. Compared with mild rosacea, moderate to severe rosacea was significantly associated with hyperlipidemia, hypertension, metabolic diseases, cardiovascular diseases, and gastroesophageal reflux disease. LIMITATIONS: This was a case-control study with moderate sample size. Associated medical conditions were self-reported and could not always be confirmed by medication use and medical records. CONCLUSIONS: Rosacea is associated with numerous systemic comorbid diseases in a skin severity-dependent manner. Physicians should be aware of these associations to provide comprehensive care to patients with rosacea, especially to those with more severe disease. PMID- 26256429 TI - Levomilnacipran Pharmacokinetics in Healthy Volunteers Versus Patients with Major Depressive Disorder and Implications for Norepinephrine and Serotonin Reuptake Inhibition. AB - PURPOSE: Levomilnacipran, a selective serotonin (5-HT) and norepinephrine (NE) reuptake inhibitor, is approved for the treatment of major depressive disorder (MDD) in adults. The objectives of this investigation were to characterize the pharmacokinetic (PK) parameters of levomilnacipran in healthy subjects and in patients with MDD and to compare the plasma concentrations observed at clinically effective doses (40-120 mg daily) in MDD patients versus in vitro inhibitory concentration values for NE and 5-HT transporters. METHODS: Data from 2 trials were analyzed: a Phase I trial (healthy volunteers received a single dose of levomilnacipran extended-release capsule [ER; 25, 50, or 100 mg], escalating multiple doses of levomilnacipran ER [25-300 mg once daily], or placebo); and a Phase III trial (adults with MDD received a fixed dose of levomilnacipran ER [40, 80, or 120 mg once daily for 8 weeks]). Plasma samples of participants were assayed to determine levomilnacipran concentrations, and PK analyses were performed. Unbound plasma concentrations of levomilnacipran in MDD patients were estimated, and inhibitory concentration values were determined by curve fitting of the in vitro data. FINDINGS: Cmax and AUC were dose proportional after single dosing (25-100 mg) and multiple dosing (across the 25-300 mg dose range) of levomilnacipran ER in healthy subjects. Dose-proportional steady-state Cmax (93, 180, and 297 ng/mL) and AUC0-tau (1520, 2935, and 4799 ng*h/mL) were also observed in patients with MDD who received levomilnacipran ER (40, 80, and 120 mg daily). Tmax was ~6 hours and was similar after single and multiple oral doses of levomilnacipran ER. Estimates of levomilnacipran concentration at 50%, 80%, and 90% inhibition were 19, 91, and 237 nM, respectively, for the 5-HT transporter, and 10, 41, and 92 nM for the NE transporter. Average unbound plasma concentrations for levomilnacipran in MDD patients treated with levomilnacipran ER 40, 80, or 120 mg daily exceeded the estimated concentration at 80% and 90% inhibition for 5-HT and NE. IMPLICATIONS: Levomilnacipran PK was dose proportional after single and multiple dosing and was similar between healthy subjects and patients with MDD. Steady-state unbound plasma concentrations of levomilnacipran across the approved dose range (40, 80, and 120 mg daily) in MDD patients were estimated to be comparable or greater than the concentrations that inhibited reuptake of NE and 5-HT by >90% and >80%, respectively, in vitro. PMID- 26256430 TI - Safety Alerts: An Observational Study in Portugal. AB - PURPOSE: The information that is available when marketing authorizations are approved is limited. Pharmacovigilance has an important role during the postauthorization period, and alerts published by national authorities allow health care professionals to be informed about new data on safety profiles. This study therefore sought to analyze all safety alerts published by the Portuguese National Authority of Medicines and Health Products I.P. (INFARMED). METHODS: We conducted an observational study of all alerts published on the INFARMED website from January 2002 through December 2014. From the data included in the alerts, the following information was abstracted: active substance name (and trade name), event that led to the alert, and the resulting safety measures. Active substances were classified according to the Anatomical Therapeutic Chemical (ATC) code. FINDINGS: A total of 562 alerts were published, and 304 were eligible for inclusion. The musculoskeletal system was the ATC code with more alerts (n = 53), followed by the nervous system (n = 42). Communication of the information and recommendations to the health care professionals and the public in general was the most frequent safety measure (n = 128), followed by changes in the Summary of the Product Characteristics and package information leaflet (n = 66). During the study period, 26 marketing authorizations were temporarily suspended and 10 were revoked. IMPLICATIONS: The knowledge of the alerts published during the postmarketing period is very useful to the health care professionals for improving prescription and use of medicines and to the scientific community for the development of new researches. PMID- 26256431 TI - Synthesis and biological activity of alkynoic acids derivatives against mycobacteria. AB - 2-Alkynoic acids have bactericidal activity against Mycobacterium smegmatis but their activity fall sharply as the length of the carbon chain increased. In this study, derivatives of 2-alkynoic acids were synthesized and tested against fast- and slow-growing mycobacteria. Their activity was first evaluated in M. smegmatis against their parental 2-alkynoic acids, as well as isoniazid, a first-line antituberculosis drug. The introduction of additional unsaturation or heteroatoms into the carbon chain enhanced the antimycobacterial activity of longer chain alkynoic acids (more than 19 carbons long). In contrast, although the modification of the carboxylic group did not improve the antimycobacterial activity, it significantly reduced the toxicity of the compounds against eukaryotic cells. Importantly, 4-(alkylthio)but-2-ynoic acids, had better bactericidal activity than the parental 2-alkynoic acids and on a par with isoniazid against the slow-grower Mycobacterium bovis BCG. These compounds had also low toxicity against eukaryotic cells, suggesting that they could be potential therapeutic agents against other types of topical mycobacterial infections causing skin diseases including Mycobacterium abscessus, Mycobacterium ulcerans, and Mycobacterium leprae. Moreover, they provide a possible scaffold for future drug development. PMID- 26256432 TI - Pancreatic paragonimiasis mimics pancreatic cystic-solid tumor--A case report. AB - Paragonimiasis is frequently misdiagnosed owing to its various and complicated clinical manifestations. Although paragonimiasis has diverse manifestations, there is no report of paragonimiasis involving the pancreas. Herein we report the first case of pancreatic paragonimiasis, which was misdiagnosed as pancreatic cystic-solid tumor by CT scan. The pancreatic lesion was finally proved to be pancreatic paragonimiasis by pathological examination and serum antibody detection. The clinical manifestations and imaging features of this patient were analyzed. Pancreatic paragonimiasis should be an important differential diagnosis for pancreatic cyst-solid lesions. PMID- 26256433 TI - Acute Hemodynamic Response to Cardiac Resynchronization in Dilated Cardiomyopathy: Effect on Late Mitral Regurgitation. AB - BACKGROUND: Functional mitral regurgitation (FMR) is associated with reduced survival in dilated cardiomyopathy (DCM). Cardiac resynchronization therapy (CRT) can improve FMR. We sought to identify the predictors of FMR improvement after CRT in DCM. METHODS: From January 2003 to December 2013, 430 DCM patients consecutively enrolled were retrospectively analyzed. Inclusion criteria were successful CRT implantation in the presence of conventional indications (i.e., left bundle branch block, left ventricular ejection fraction <=35%, New York Heart Association functional class >=II) and moderate-to-severe FMR at the time of procedure. Early echocardiographic evaluation after CRT implantation (median 2.5 days) has been performed in each patient. Improvement in FMR (absent/mild) at midterm (7 months; interquartile range 4-10) was considered as the primary study end point. RESULTS: A total of 44 patients (10% of the overall cohort) were included. A significant reduction in FMR severity was observed in 21 patients (48%) at midterm after CRT (median time 7 months). No preimplantation variables predicted FMR evolution, but FMR improvement at midterm was strongly predicted by an acute favorable hemodynamic response (persistence/development of normal right ventricular function and 10-mm Hg decrease or normalization [<=35 mm Hg] of systolic pulmonary artery pressure) at postimplantation echocardiography (odds ratio: 13.7; 95% confidence interval: 1.27-42.8; P = 0.016). FMR improvement at midterm was stable during follow-up and was associated with superior long-term transplant-free survival (P = 0.022). CONCLUSIONS: Stable FMR improvement frequently occurs after CRT implantation in DCM and is associated with improved transplant-free survival. Echocardiographic evaluation of acute hemodynamic response to CRT is helpful to early identification of the favorable FMR evolution. PMID- 26256434 TI - Inactivation of Staphylococcus aureus in Oat and Soya Drinks by Enterocin AS-48 in Combination with Other Antimicrobials. AB - The presence of toxicogenic Staphylococcus aureus in foods and the dissemination of methicillin-resistant S. aureus (MRSA) in the food chain are matters of concern. In the present study, the circular bacteriocin enterocin AS-48, applied singly or in combination with phenolic compounds (carvacrol, eugenol, geraniol, and citral) or with 2-nitro-1-propanol (2NPOH), was investigated in the control of a cocktail made from 1 methicillin-sensitive and 1 MRSA strains inoculated on commercial oat and soya drinks. Enterocin AS-48 exhibited low bactericidal activity against staphylococci in the drinks investigated when applied singly. The combinations of sub-inhibitory concentrations of enterocin AS-48 (25 MUg/mL) and phenolic compounds or 2NPOH caused complete inactivation of staphylococci in the drinks within 24 h of incubation at 22 degrees C. When tested in oat and soya drinks stored for 7 d at 10 degrees C, enterocin AS-48 (25 MUg/mL) in combination with 2NPOH (5.5 mM) reduced viable counts rapidly in the case of oat drink (4.2 log cycles after 12 h) or slowly in soya drink (3.8 log cycles after 3 d). The same combined treatment applied on drinks stored at 22 degrees C achieved a fast inactivation of staphylococci within 12 to 24 h in both drinks, and no viable staphylococci were detected for up to 7 d of storage. Results from the study highlight the potential of enterocin AS-48 in combination with 2NPOH for inactivation of staphylococci. PMID- 26256435 TI - Transversally oriented pedicled perforator flaps: A reliable alternative for lower leg reconstruction. AB - BACKGROUND: The use of a transverse pattern for perforator flap design and its possible clinical applications in the field of lower leg reconstruction are previously unreported in the medical literature. The purpose of this report is to describe our clinical experience with the use of transversally oriented pedicled perforator flaps in lower leg reconstruction. PATIENTS AND METHODS: Seven patients underwent lower leg reconstruction with transversally oriented pedicled perforator flaps. Patients age ranged from 42 to 68 years. All defects resulted from skin cancer ablation. Defect sizes ranged from 9 * 5 to 5 * 2.5 cm. The technique was applied to patients presenting with vertically oriented, long, and narrow defects, not feasible for primary closure, with the only audible perforators detected at a significant distance from the wound. RESULTS: All flaps were based on a single perforator vessel. One of them was converted to a perforator-plus peninsular flap design, which retained an additional source of blood supply from the opposite skin bridge. The flaps were always mobilized in V Y fashion. Donor sites were always closed primarily. Flap dimensions ranged from 15 * 7 to 8 * 3.5 cm. Operative time ranged from 40 to 90 minutes. All flaps survived uneventfully. Follow-up ranged from 6 months to 2 years. All patients were satisfied with the surgical outcome. CONCLUSIONS: The use of transversally oriented pedicled perforator flaps proved to be a reliable alternative option to reconstruct small to medium size defects of the lower leg. PMID- 26256436 TI - Response assessment for HCC patients treated with repeated TACE: The optimal time point is still an open issue. PMID- 26256438 TI - Changing incidence patterns of hepatocellular carcinoma among age groups in Taiwan. AB - BACKGROUND & AIMS: This study examined and compared the incidence patterns of hepatocellular carcinoma among age groups in Taiwan, 30 years after a universal hepatitis B virus immunization program was launched. METHODS: Data for hepatocellular carcinoma diagnosed in 2003-2011 were collected from the population-based Taiwan Cancer Registry. Age-standardized incidence rates were calculated to analyze and compare the changes in incidence rates and trends. More specific analyses were performed on four age groups separated by sex. RESULTS: A total of 82,856 patients were diagnosed with hepatocellular carcinoma in 2003 2011 in Taiwan, yielding an age-standardized incidence rate of 32.97 per 100,000 person-years. Hepatocellular carcinoma was predominantly diagnosed in middle-aged adults (50.1%) and elderly people (49.1%), in contrast to the low incidences in children (0.04%) and adolescents and young adults (0.8%). Striking variations in trends were found for children (annual percent change: -16.6%, 2003-2010) and adolescents and young adults (annual percent change: -7.9%, 2003-2011). The incidence rate of hepatocellular carcinoma in children decreased to zero in 2011; only a slight decline in trends occurred for the middle-aged group (annual percent change: -2%, 2003-2011), and a slight upward trend was observed for elderly people (1.3%), specifically in women (1.7%). CONCLUSIONS: In Taiwan, hepatitis B virus-related hepatocellular carcinoma was nearly eradicated in children in 2011. The findings on age-specific incidence patterns and trends of hepatocellular carcinoma suggest that different control strategies for treating this devastating disease in the future be made according to age. PMID- 26256437 TI - Implications of microbiota and bile acid in liver injury and regeneration. AB - Studies examining the mechanisms by which the liver incurs injury and then regenerates usually focus on factors and pathways directly within the liver, neglecting the signaling derived from the gut-liver axis. The intestinal content is rich in microorganisms as well as metabolites generated from both the host and colonizing bacteria. Through the gut-liver axis, this complex "soup" exerts an immense impact on liver integrity and function. This review article summarizes data published in the past 30 years demonstrating the signaling derived from the gut-liver axis in relation to liver injury and regeneration. Due to the intricate networks of implicated pathways as well as scarcity of available mechanistic data, it seems that nutrigenomic, metabolomics, and microbiota profiling approaches are warranted to provide a better understanding regarding the interplay and impact between nutrition, bacteria, and host response in influencing liver function and healing. Therefore elucidating the possible molecular mechanisms that link microbiota alteration to host physiological response and vice versa. PMID- 26256439 TI - Streptomyces natalensis programmed cell death and morphological differentiation are dependent on oxidative stress. AB - Streptomyces are aerobic Gram-positive bacteria characterized by a complex life cycle that includes hyphae differentiation and spore formation. Morphological differentiation is triggered by stressful conditions and takes place in a pro oxidant environment, which sets the basis for an involvement of the oxidative stress response in this cellular process. Characterization of the phenotypic traits of Streptomyces natalensis DeltakatA1 (mono-functional catalase) and DeltacatR (Fur-like repressor of katA1 expression) strains in solid medium revealed that both mutants had an impaired morphological development process. The sub-lethal oxidative stress caused by the absence of KatA1 resulted in the formation of a highly proliferative and undifferentiated vegetative mycelium, whereas de-repression of CatR regulon, from which KatA1 is the only known representative, resulted in the formation of scarce aerial mycelium. Both mutant strains had the transcription of genes associated with aerial mycelium formation and biosynthesis of the hyphae hydrophobic layer down-regulated. The first round of the programmed cell death (PCD) was inhibited in both strains which caused the prevalence of the transient primary mycelium (MI) over secondary mycelium (MII). Our data shows that the first round of PCD and morphological differentiation in S. natalensis is dependent on oxidative stress in the right amount at the right time. PMID- 26256440 TI - Distinct effects of novel naphtoquinone-based triazoles in human leukaemic cell lines. AB - OBJECTIVES: The aim of this study was to investigate the cytotoxic effect of new 1,4-naphthoquinone- 1,2,3-triazoles, named C2 to C8 triazole derivatives, towards human cancer cell lines. METHODS: The effect on cell viability was assessed by MTT and propidium iodide assays. The cytotoxic effect of C2 and C3 in K562 and HL 60 cells were analyzed by flow cytometry, DNA fragmentation and reactive oxygen species (ROS) production. Western blot and q-PCR procedures were also performed. KEY FINDINGS: C2 and C3 inhibited both K562 and HL-60 cells growth in a concentration-dependent manner. C2 presented the highest cytotoxic activity with an IC50 of approximately 14 MUm and 41 MUm for HL-60 and K562 cells, respectively, while being less toxic to normal peripheral blood monocyte cells. Both derivatives induced cellular changes in HL-60 cells, characteristic of apoptosis, such as mitochondrial membrane depolarization, phosphatidylserine externalization, increasing sub-G1 phase, DNA fragmentation, downregulating Bcl-2 protein and upregulating Bax protein. In K562 cells, C2 and C3 induced S-phase arrest of cell cycle, which was associated with upregulation of p21. The effect of these derivatives in HL-60 cells can be related to the ROS intracellular level. CONCLUSION: Taken together our results showed that C2 and C3 triazole derivatives presented the best potential for drug design. PMID- 26256441 TI - Does quality of life depend on speech recognition performance for adult cochlear implant users? AB - OBJECTIVES/HYPOTHESIS: Current postoperative clinical outcome measures for adults receiving cochlear implants (CIs) consist of testing speech recognition, primarily under quiet conditions. However, it is strongly suspected that results on these measures may not adequately reflect patients' quality of life (QOL) using their implants. This study aimed to evaluate whether QOL for CI users depends on speech recognition performance. STUDY DESIGN: Twenty-three postlingually deafened adults with CIs were assessed. METHODS: Participants were tested for speech recognition (Central Institute for the Deaf word and AzBio sentence recognition in quiet) and completed three QOL measures-the Nijmegen Cochlear Implant Questionnaire; either the Hearing Handicap Inventory for Adults or the Hearing Handicap Inventory for the Elderly; and the Speech, Spatial and Qualities of Hearing Scale questionnaires-to assess a variety of QOL factors. Correlations were sought between speech recognition and QOL scores. Demographics, audiologic history, language, and cognitive skills were also examined as potential predictors of QOL. RESULTS: Only a few QOL scores significantly correlated with postoperative sentence or word recognition in quiet, and correlations were primarily isolated to speech-related subscales on QOL measures. Poorer pre- and postoperative unaided hearing predicted better QOL. Socioeconomic status, duration of deafness, age at implantation, duration of CI use, reading ability, vocabulary size, and cognitive status did not consistently predict QOL scores. CONCLUSION: For adult, postlingually deafened CI users, clinical speech recognition measures in quiet do not correlate broadly with QOL. Results suggest the need for additional outcome measures of the benefits and limitations of cochlear implantation. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:699-706, 2016. PMID- 26256442 TI - Longitudinal annular displacement by M-mode (MAPSE and TAPSE) in twin-to-twin transfusion syndrome before and after laser surgery. AB - OBJECTIVE: To evaluate mitral and tricuspid annular plane systolic excursion (MAPSE and TAPSE) in fetuses with twin-to-twin transfusion syndrome (TTTS) before and after laser therapy. METHODS: A prospective study in 24 fetal pairs with TTTS evaluated 24 h before and within 48 h after fetoscopy and 13 gestational age matched normal monochorionic fetal pairs. MAPSE and TAPSE were measured in an apical or basal four-chamber view by placing the M-mode cursor at the lateral valve ring. RESULTS: Mean preoperative MAPSE (controls 3.6 +/- 1.3 mm vs. donors 2.7 +/- 0.8 mm vs. recipients 2.8 mm +/- 0.9; P < 0.001) and TAPSE (controls 4.4 +/- 1.5 mm vs. donors 3.3 +/- 1 mm vs. recipients 3.6 +/- 1.1 mm; P < 0.001) values were significantly reduced in both TTTS fetuses. When subdividing according to TTTS stages, changes were significant in both stage I-II and III-IV subgroups, although differences were more pronounced in the latter. All observations remained unchanged 48 h post-fetoscopy. CONCLUSION: Both recipient and donor fetuses had decreased global longitudinal motion, even in early TTTS stages. PMID- 26256443 TI - Starved human T lymphocytes keep fighting. AB - Cellular metabolism is emerging as a key determinant of T-lymphocyte differentiation and function. While this new paradigm has been primarily characterized in murine systems, research is now characterizing a role for different aspects of cellular metabolism in controlling human T-lymphocyte biology. In this issue of the European Journal of Immunology, Renner et al. [Eur. J. Immunol. 2015. 45: 2504-2516] analyze the glycolytic and mitochondrial activity of activated human CD4(+) and CD8(+) T cells, and correlate it to T-cell function. The authors show that although neither glucose deprivation nor mitochondrial restriction affects cytokine production, the glycolytic inhibitor 2 deoxyglucose severely affects T-cell function. PMID- 26256444 TI - Nonstructural carbohydrate dynamics of lodgepole pine dying from mountain pine beetle attack. AB - Bark beetle outbreaks are an important cause of tree death, but the process by which trees die remains poorly understood. The effect of beetle attack on whole tree nonstructural carbohydrate (NSC) dynamics is particularly unclear, despite the potential role of carbohydrates in plant defense and survival. We monitored NSC dynamics of all organs in attacked and protected lodgepole pines (Pinus contorta) during a mountain pine beetle (Dendroctonus ponderosae) outbreak in British Columbia, starting before beetle flight in June 2011 through October 2012, when most attacked trees had died. Following attack, NSC concentrations were first reduced in the attacked region of the bole. The first NSC reduction in a distant organ appeared in the needles at the end of 2011, while branch and root NSC did not decline until much later in 2012. Attacked trees that were still alive in October 2012 had less beetle damage, which was negatively correlated with initial bark sugar concentrations in the attack region. The NSC dynamics of dying trees indicate that trees were killed by a loss of water conduction and not girdling. Further, our results identify locally reduced carbohydrate availability as an important mechanism by which stressors like drought may increase tree susceptibility to biotic attack. PMID- 26256445 TI - Ulcerative colitis outpatient management: development and evaluation of tools to support primary care practitioners. AB - BACKGROUND: Current models of care for ulcerative colitis (UC) across healthcare systems are inconsistent with a paucity of existing guidelines or supportive tools for outpatient management. AIMS: This study aimed to produce and evaluate evidence-based outpatient management tools for UC to guide primary care practitioners and patients in clinical decision-making. METHODS: Three tools were developed after identifying current gaps in the provision of healthcare services for patients with UC at a Clinical Insights Meeting in 2013. Draft designs were further refined through consultation and consolidation of feedback by the steering committee. Final drafts were developed following feasibility testing in three key stakeholder groups (gastroenterologists, general practitioners and patients) by questionnaire. The tools were officially launched into mainstream use in Australia in 2014. RESULTS: Three quarters of all respondents liked the layout and content of each tool. Minimal safety concerns were aired and those, along with pieces of information that were felt to be omitted, that were reviewed by the steering committee and incorporated into the final documents. The majority (over 80%) of respondents felt that the tools would be useful and would improve outpatient management of UC. CONCLUSION: Evidence-based outpatient clinical management tools for UC can be developed. The concept and end-product have been well received by all stakeholder groups. These tools should support non specialist clinicians to optimise UC management and empower patients by facilitating them to safely self-manage and identify when medical support is needed. PMID- 26256446 TI - Screw Loosening and Pelvic Canal Narrowing After Lateral Plating of Feline Ilial Fractures With Locking and Nonlocking Plates. AB - OBJECTIVE: To compare the frequency of complications, including screw loosening and pelvic canal narrowing, associated with dynamic compression plating, locking plating, and double locking plating of ilial fractures in cats. STUDY DESIGN: Historical cohort study. METHODS: The radiographs and medical records of cats with pelvic fractures that were presented between 2004 and 2013 were reviewed. The cases were categorized based on the plate type and number as dynamic compression plate (DCP), single locking plate (LPS) and double locking plates (dLPS). The frequency of screw loosening was compared across categories using a Fisher's exact test. The change in pelvic alignment, described by the change in sacral index (postoperative sacral index-followup sacral index), was compared across plate categories using ANOVA. RESULTS: The frequency of screw loosening for DCP (5/10) was significantly higher than LPS (1/13) and dLPS (0/11) (P = .05, P = .012, respectively). There was no significant difference in the SI change across plate categories. The mean change in sacral index for DCP was -0.11 (95%CI -0.25 to 0.03), for LPS was 0.0007 (95%CI -0.07 to 0.08), and for dLPS was -0.01 (95%CI -0.04 to 0.02). None of the cats showed constipation postoperatively. CONCLUSION: Screw loosening occurred less often but the change in pelvic canal alignment was not significantly different in ilial fractures repaired with LPS or dLPS compared to ilial fractures repaired with DCP. Locking plating of ilial fractures in cats may offer advantages compared to nonlocking plating. PMID- 26256447 TI - Biomimetic microstructural reorganization during suture retention strength evaluation of electrospun vascular scaffolds. AB - Suture retention strength (SRS) is commonly used as a measure the ability of sutures to adhere implants to surrounding tissue. While SRS is widely employed, surprisingly its effects on graft microstructure have not been characterized. This is particularly germane to the broad utilization of electrospun implants in tissue engineering. These implants need to retain their initial nanoscale topography while simultaneously preserving clinically critical mechanical properties. We examined the suture-driven microstructural deformation of polycaprolactone electrospun to form both square and tubular SRS samples. The impact of fiber orientation (generally parallel or random orientation, orthogonally aligned) on the SRS of these vascular tissue equivalents was analyzed and compared to native and decellularized porcine vasculature. The initial state of the fiber clearly dictates the overall efficiency of scaffold utilization. SRS values for as-spun fibers at a thickness of 300 MUm were found to be in the range of 1.59-4.78 N for the three orientations. Unexpectedly, random fibers provided the optimal SRS values based on both resistance to suture motion and the percentage of scaffold involvement. A "V-shaped" failure morphology is observed for both electrospun scaffolds and native tissue during SRS testing. Post-test fiber alignment in the tensile direction was visible in all initial fiber orientations similar to that of native tissue. These findings are significant as they allow us to employ new, counterintuitive biomimetic design criteria for nanofiber-based scaffolds in which reliable mechanical integration with the surrounding tissues via suture-based methods is important. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1525-1534, 2016. PMID- 26256448 TI - Histone methylation-mediated silencing of miR-139 enhances invasion of non-small cell lung cancer. AB - MicroRNA expression is frequently altered in human cancers, and some microRNAs act as oncogenes or tumor suppressors. MiR-139-5p (denoted thereafter as miR-139) has recently been reported to function as a tumor suppressor in several types of human cancer (hepatocellular carcinoma, colorectal cancer, breast cancer, and gastric cancer), but its function in non-small-cell lung cancer (NSCLC) and the mechanism of its suppression have not been studied in detail. MiR-139 was suppressed frequently in primary NSCLCs. MiR-139 is located within the intron of PDE2A and its expression was significantly correlated with the expression of PDE2A. A chromatin immunoprecipitation assay revealed that miR-139 was epigenetically silenced by histone H3 lysine 27 trimethylation (H3K27me3) of its host gene PDE2A and this process was independent of promoter DNA methylation. Pharmacological inhibition of both histone methylation and deacetylation-induced miR-139 with its host gene PDE2A. Ectopic expression of miR-139 in lung cancer cell lines did not affect the proliferation nor the migration but significantly suppressed the invasion through the extracellular matrix. In primary NSCLCs, decreased expression of miR-139 was significantly associated with distant lymph node metastasis and histological invasiveness (lymphatic invasion and vascular invasion) on both univariate and multivariate analyses. Collectively, these results suggest that H3K27me3-mediated silencing of miR-139 enhances an invasive and metastatic phenotype of NSCLC. PMID- 26256449 TI - The influence of reward and punishment on motor learning. PMID- 26256450 TI - Polypoid extrahepatic bile duct carcinoma morphologically indistinguishable from benign giant cell tumor. PMID- 26256451 TI - Does job satisfaction mediate the relationship between healthy work environment and care quality? AB - BACKGROUND: A healthy work environment can increase nurse-reported job satisfaction and patient care outcomes. Yet the associations between healthy work environment, nurse job satisfaction and QC have not been comprehensively examined in Chinese ICUs. AIM: To investigate the mediating effect of nurse job satisfaction on the relationship between healthy work environment and nurse reported quality of care (QC) in Chinese intensive care units (ICUs). METHODS: A total of 706 nurses were recruited from 28 ICUs of 14 tertiary hospitals. The nurses completed self-reported questionnaires to evaluate healthy work environment, job satisfaction and quality of patient care. Mediation analysis was conducted to explore the mediating effect between nurse-reported healthy work environment and QC. RESULTS: Nurse work environment showed positive correlations with nurse-reported QC in the ICUs. Nurse-reported job satisfaction showed full mediating effects between healthy work environment and QC in the medical-surgical ICUs, surgical ICUs and neonatal/paediatric ICUs and indicated a partial mediating effect in the medical ICUs. RELEVANCE TO CLINICAL PRACTICE: Significant mediating effects of nurse job satisfaction provide more support for thinking about how to use this mediator to increase nurse and patient care outcomes. Nurse administrators can design interventions to increase nurse work environment and patient care outcomes with this mediating factor addressed. PMID- 26256452 TI - Ventricular Support With Extracorporeal Membrane Oxygenation: Beyond Cardiogenic Shock Treatment. PMID- 26256453 TI - Introduction of Innovations in Heart Disease in Spain: InnovaSEC. PMID- 26256454 TI - Raman spectroscopy for detecting supported planar lipid bilayers composed of ganglioside-GM1/sphingomyelin/cholesterol in the presence of amyloid-beta. AB - The aggregation and fibril formation of amyloid beta(Abeta) peptides onto a ganglioside-GM1-containing lipid membrane is a cause of neurodegenerative diseases. The mechanism of the initial binding and the conformational changes of Abeta on the membrane should be clarified. Fluorescence microscopy and Raman spectroscopy have been performed to investigate the supporting planar lipid bilayers (SPBs) composed of ganglioside-GM1, sphingomyelin and cholesterol. It is demonstrated that the SPBs are in a liquid-crystalline state when placed on mica, and increasing the amount of ganglioside-GM1 can decrease the lateral interaction between the acyl chains of the SPBs. It has been found that Abeta(1-40) initially interacts with the galactose ring of the ganglioside-GM1 head group, leading to its binding and gradual aggregation on the membrane surface. The obvious change observed in Raman spectroscopy in the nu(C-H) region confirms that the hydrophobic C-terminal of Abeta(1-40) inserts itself into the hydrophobic part of the SPBs. The Raman data indicate that alpha-helix and beta-sheet structures of Abeta(1-40) increase and coexist over longer time frames. Based on these results, a model was proposed to describe the mechanism of the conformational changes and the aggregation of Abeta(1-40) that are mediated by ganglioside-GM1-containing SPBs. PMID- 26256456 TI - An update on methods for revascularization and expansion of the TASC lesion classification to include below-the-knee arteries: A supplement to the inter society consensus for the management of peripheral arterial disease (TASC II): The TASC steering committee. AB - The Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC) guidelines were last updated in 2007 (TASC II) and represented the collaboration of international vascular specialties involved in the management of patients with peripheral arterial disease (PAD). Since the publication of TASC II, there have been innovations in endovascular revascularization strategies for patients with PAD. The intent of this publication is to provide a complete anatomic lower limb TASC lesion classification, including the infrapopliteal segment, and an updated literature review of new endovascular techniques and practice patterns employed by vascular specialists today. PMID- 26256455 TI - A joint latent class analysis for adjusting survival bias with application to a trauma transfusion study. AB - There is no clear classification rule to rapidly identify trauma patients who are severely hemorrhaging and may need substantial blood transfusions. Massive transfusion (MT), defined as the transfusion of at least 10 units of red blood cells within 24 h of hospital admission, has served as a conventional surrogate that has been used to develop early predictive algorithms and establish criteria for ordering an MT protocol from the blood bank. However, the conventional MT rule is a poor proxy, because it is likely to misclassify many severely hemorrhaging trauma patients as they could die before receiving the 10th red blood cells transfusion. In this article, we propose to use a latent class model to obtain a more accurate and complete metric in the presence of early death. Our new approach incorporates baseline patient information from the time of hospital admission, by combining respective models for survival time and usage of blood products transfused within the framework of latent class analysis. To account for statistical challenges, caused by induced dependent censoring inherent in 24-h sums of transfusions, we propose to estimate an improved standard via a pseudo likelihood function using an expectation-maximization algorithm with the inverse weighting principle. We evaluated the performance of our new standard in simulation studies and compared with the conventional MT definition using actual patient data from the Prospective Observational Multicenter Major Trauma Transfusion study. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26256457 TI - Diagnosis and treatment of dementia in neurology outpatient departments of general hospitals in China. AB - INTRODUCTION: The status of dementia diagnosis and treatment of neurology outpatients in general hospitals in China remains unclear. METHODS: From neurology outpatients at 36 randomly selected hospitals, we first collected baseline data concerning the number of dementia doctors, memory clinics, and patients diagnosed with dementia. In stage 2, we intervened based on drawbacks discovered in stage 1, implementing a dementia initiative program. In stage 3, we reinvestigated the outpatients to determine the effects of intervention. RESULTS: After intervention, all 36 hospitals had established memory clinics (205 dementia doctors) compared with only 6 (47 dementia doctors) before intervention. The percentage of patients diagnosed with dementia significantly increased from 0.10% (536 dementia patients of 553,986 outpatients) in stage 1 to 0.41% (2482 dementia patients of 599,214 outpatients) in stage 3. DISCUSSION: Proper diagnosis and treatment are unavailable to many dementia patients because of a lack of dementia doctors and memory clinics in China. PMID- 26256458 TI - Long-term remission in idiopathic Castleman's disease with tocilizumab followed by consolidation with high-dose melphalan--two case studies. AB - Multicentric Castleman's disease (MCD) is an uncommon lymphoproliferative disorder, often associated with a clinically aggressive behavior. No standard treatment has been established, but patients are usually treated with lymphoma type regimens such as rituximab or combination chemotherapy. Recently, immunotherapies targeting IL-6 have proven effective and have been approved for this indication. However, these agents require long-term administration. Here, we describe the clinical course of two patients, refractory to rituximab and chemotherapy, showing long-term remission (18 and 24 months), following an induction phase with tocilizumab (an anti-IL-6 receptor antibody) and a consolidative phase with high-dose melphalan accompanied by autologous stem cell support. This may prove to be an effective option for this group of patients with an orphan disorder. PMID- 26256460 TI - The lipid raft proteome of Borrelia burgdorferi. AB - Eukaryotic lipid rafts are membrane microdomains that have significant amounts of cholesterol and a selective set of proteins that have been associated with multiple biological functions. The Lyme disease agent, Borrelia burgdorferi, is one of an increasing number of bacterial pathogens that incorporates cholesterol onto its membrane, and form cholesterol glycolipid domains that possess all the hallmarks of eukaryotic lipid rafts. In this study, we isolated lipid rafts from cultured B. burgdorferi as a detergent resistant membrane (DRM) fraction on density gradients, and characterized those molecules that partitioned exclusively or are highly enriched in these domains. Cholesterol glycolipids, the previously known raft-associated lipoproteins OspA and OpsB, and cholera toxin partitioned into the lipid rafts fraction indicating compatibility with components of the DRM. The proteome of lipid rafts was analyzed by a combination of LC-MS/MS or MudPIT. Identified proteins were analyzed in silico for parameters that included localization, isoelectric point, molecular mass and biological function. The proteome provided a consistent pattern of lipoproteins, proteases and their substrates, sensing molecules and prokaryotic homologs of eukaryotic lipid rafts. This study provides the first analysis of a prokaryotic lipid raft and has relevance for the biology of Borrelia, other pathogenic bacteria, as well as for the evolution of these structures. All MS data have been deposited in the ProteomeXchange with identifier PXD002365 (http://proteomecentral.proteomexchange.org/dataset/PXD002365). PMID- 26256459 TI - Viscoelastic measurements of platelet function, not fibrinogen function, predicts sensitivity to tissue-type plasminogen activator in trauma patients. AB - BACKGROUND: Systemic hyperfibrinolysis is a lethal phenotype of trauma-induced coagulopathy. Its pathogenesis is poorly understood. Recent studies have support a central role of platelets in hemostasis and in fibrinolysis regulation, implying that platelet impairment is integral to the development of postinjury systemic hyperfibrinolysis. OBJECTIVE: The objective of this study was to identify if platelet function is associated with blood clot sensitivity to fibrinolysis. We hypothesize that platelet impairment of the ADP pathway correlates with fibrinolysis sensitivity in trauma patients. METHODS: A prospective observational study of patients meeting the criteria for the highest level of activation at an urban trauma center was performed. Viscoelastic parameters associated with platelet function (maximum amplitude [MA]) were measured with native thrombelastography (TEG), and TEG platelet mapping of the ADP pathway (ADP-MA). The contribution of fibrinogen to clotting was measured with TEG (angle) and the TEG functional fibrinogen (FF) assay (FF-MA). Another TEG assay containing tissue-type plasminogen activator (t-PA) (75 ng mL(-1) ) was used to assess clot sensitivity to an exogenous fibrinolytic stimulus by use of the TEG lysis at 30 min (LY30) variable. Multivariate linear regression was used to identify which TEG variable correlated with t-PA-LY30 (quantification of fibrinolysis sensitivity). RESULTS: Fifty-eight trauma patients were included in the analysis, with a median injury severity score of 17 and a base deficit of 6 mEq L(-1) . TEG parameters that significantly predicted t-PA-LY30 were related to platelet function (ADP-MA, P = 0.001; MA, P < 0.001) but not to fibrinogen (FF MA, P = 0.773; angle, P = 0.083). Clinical predictors of platelet ADP impairment included calcium level (P = 0.001), base deficit (P = 0.001), and injury severity (P = 0.001). RESULTS AND CONCLUSIONS: Platelet impairment of the ADP pathway is associated with increased sensitivity to t-PA. ADP pathway inhibition in platelets may be an early step in the pathogenesis of systemic hyperfibrinolysis. PMID- 26256461 TI - Bevacizumab for Malignant Brain Gliomas. Which is the Current Evidence? AB - Recently, the improvement of innovative medications named focused treatments represents the consequence of a superior knowledge of the procedures implicated in the modification of physiological tissues in tumor. Focused treatment is known as the therapy which uses specific substances that affect selective mechanisms implicated in tumorigenesis and tumor development. Angiogenesis is important for tumor development and distant metastatic disease and represents a significant aim for modern biological substances. Bevacizumab belongs to humanized recombinant antibody family which obviates vascular endothelial growth factor (VEGF) receptor fastening, and suspending genesis of new vessels and tumor development. Bevacizumab represents the primary antiangiogenic treatment authorized for usage in tumor and has FDA authorization to treat the recurrent glioblastoma multiform since 2009. Bevacizumab's efficiency for treating malignant brain gliomas along with correlated patent appliances related to this agent is discussed below. PMID- 26256462 TI - Just How Useful Are Health Rankings? PMID- 26256463 TI - Efficacy and Safety of Endoscopic Submucosal Dissection for Colorectal Carcinoids. AB - BACKGROUND & AIMS: Although endoscopic submucosal dissection (ESD) of colorectal carcinoids is increasing, little is known about long-term outcomes of patients. We investigated the efficacy and safety of ESD of colorectal carcinoids and evaluated long-term outcomes, including local recurrence and metastasis. METHODS: We performed a retrospective analysis of data collected from 239 consecutive patients with colorectal carcinoids <20 mm who underwent endoscopic ultrasonography (to evaluate the size of tumor and the depth of invasion), followed by ESD from January 2007 through October 2012 at the Zhongshan Hospital of Fudan University. Histology and patient data were collected during a median follow-up period of 52 months (range, 25-94 months) to determine tumor stage and type, completeness of resection, complications, tumor recurrence, and distant metastasis. RESULTS: En bloc resection was achieved for all of the 239 treated lesions; tumor tissues were completely resected for 216 of the lesions (90.38%). Eight patients had ESD-related complications (3.35%). As more ESDs were performed by endoscopists, the rate of complete tumor resection increased, and the rate of complications decreased. ESD of carcinoids in colon increased the risk of non-R0 resection and the rate of complications. During the follow-up period, all patients remained free from local recurrence. However, distant metastases were detected in 6 patients (2.51%); lymphovascular invasion was a risk factor for metastasis. CONCLUSIONS: ESD is effective for the resection of rectal carcinoids <20 mm and causes complications in less than 4% of patients. ESD for colonic carcinoids is feasible but associated with a higher non-R0 resection rate and a trend toward higher complications risk. Tumor features and stage determine risk for distant metastasis, so long-term follow-up is essential. PMID- 26256464 TI - Efficacy of Psychosocial Interventions in Inducing and Maintaining Alcohol Abstinence in Patients With Chronic Liver Disease: A Systematic Review. AB - BACKGROUND & AIMS: We conducted a systematic review of efficacy of psychosocial interventions in inducing or maintaining alcohol abstinence in patients with chronic liver disease (CLD) and alcohol use disorder (AUD). METHODS: We performed structured keyword searches in PubMed, PsychINFO, and MEDLINE for original research articles that were published from January 1983 through November 2014 that evaluated the use of psychosocial interventions to induce or maintain alcohol abstinence in patients with CLD and AUD. RESULTS: We identified 13 eligible studies that comprised 1945 patients; 5 were randomized controlled trials (RCTs). Delivered therapies included motivational enhancement therapy, cognitive behavioral therapy (CBT), motivational interviewing, supportive therapy, and psychoeducation either alone or in combination in the intervention group and general health education or treatment as usual in the control group. All studies of induction of abstinence (4 RCTs and 6 observational studies) reported an increase in abstinence among participants in the intervention and control groups. Only an integrated therapy that combined CBT and motivational enhancement therapy with comprehensive medical care, delivered during a period of 2 years, produced a significant increase in abstinence (74% increase in intervention group vs 48% increase in control group, P = .02), which was reported in 1 RCT. All studies of maintenance of abstinence (1 RCT and 2 observational studies) observed recidivism in the intervention and control groups. Only an integrated therapy that combined medical care with CBT produced a significantly smaller rate of recidivism (32.7% in integrated CBT group vs 75% in control group, P = .03), which was reported from 1 observational study. However, data were not collected for more than 2 years on outcomes of patients with CLD and AUD. CONCLUSIONS: In a systematic analysis of studies of interventions to induce or maintain alcohol abstinence in patients with CLD and AUD, integrated combination psychotherapy with CBT, motivational enhancement therapy, and comprehensive medical care increased alcohol abstinence. No psychosocial intervention was successful in maintaining abstinence, but an integrated therapy with CBT and medical care appears to reduce recidivism. PMID- 26256465 TI - Acceptance rate of long-acting injection after short information: a survey in patients with first- and multiple-episode psychoses and their caregivers. AB - AIM: The aim of this study was to investigate the acceptance rates of long-acting injection (LAI) in patients with first- and multiple-episode psychoses before and after providing concise information about LAI to the patients and their caregivers. Additionally, predictors of choosing LAI and the reasons for reluctance to accept LAI were also evaluated. METHODS: The survey included the questionnaire about participants' demographic characteristics, prior knowledge about LAI, attitude towards the importance of medication or psychotherapy and acceptance for LAI - treatment. The acceptance rate for LAI was re-evaluated after providing short information about current LAI or to the hypothetical questions like if there are a 3-ms lasting injection or the cost of injection is cheap. RESULT: This study included 161 patients and 113 caregivers who completed a cross-sectional survey. Following exposure to LAI information, acceptance rates for this method of treatment did not change in all groups. However, acceptance rates increased significantly when asked if the cost of LAI was cheaper than the current oral medication and the effect of LAI lasted for 3 months. Significant predictors of acceptance of LAI in patients with first-episode psychosis were prior knowledge about LAI, attitudes towards the importance of medication and discomfort due to medication side-effects. CONCLUSION: The present study demonstrated that a substantial portion of patients with first- and multiple episode psychoses and their caregivers prefer LAI over their current oral medication. The acceptance of LAI was not increased by providing succinct information concerning this method of treatment. PMID- 26256466 TI - Pharmacokinetics in neonatal prescribing: evidence base, paradigms and the future. AB - Paediatric patients, particularly preterm neonates, present many pharmacological challenges. Due to the difficulty in conducting clinical trials in these populations dosing information is often extrapolated from adult populations. As the processes of absorption, distribution, metabolism and excretion of drugs change throughout growth and development extrapolation presents risk of over or underestimating the doses required. Information about the development these processes, particularly drug metabolism pathways, is still limited with weight based dose adjustment presenting the best method of estimating pharmacokinetic changes due to growth and development. New innovations in pharmacokinetic research, such as population pharmacokinetic modelling, present unique opportunities to conduct clinical trials in these populations improving the safety and effectiveness of the drugs used. More research is required into this area to ensure the best outcomes for our most vulnerable patients. PMID- 26256468 TI - Kidney transplant in pediatric patients with severe bladder pathology. AB - The aim of the current study was to compare results in pediatric renal transplantation of patients with and without SBP. Between 2001 and 2013, a total of 168 kidney transplants were performed at our center. A retrospective analysis was performed and recipients were divided into two groups: NB and SBP. Incidence of surgical complications after procedure, and graft and patient survival were evaluated. A total of 155 recipients (92%) with complete data were analyzed, and 13 recipients that had had previous bladder surgeries were excluded (11 with VUR surgery and two with previous kidney transplants), of the 155 recipients: 123 (79%) patients had NB, and 32 (21%) patients had SBP, with a median follow-up of 60 (1-137) and 52 (1-144) months, respectively. Among post-transplant complications, UTI (68.8% vs. 23%, p < 0.0001) and symptomatic VUR to the graft (40.6% vs. 7.3%, p < 0.0001) were significantly higher in the SBP group. There was no significant difference in overall graft and patient survival between groups. Renal transplantation is safe in pediatric recipients with SBP; however, urologic complications such as UTI and VUR were significantly higher in this group. Graft and patient survival was similar in SBP and NB groups. PMID- 26256467 TI - Genome-wide association study of triglyceride response to a high-fat meal among participants of the NHLBI Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). AB - OBJECTIVE: The triglyceride (TG) response to a high-fat meal (postprandial lipemia, PPL) affects cardiovascular disease risk and is influenced by genes and environment. Genes involved in lipid metabolism have dominated genetic studies of PPL TG response. We sought to elucidate common genetic variants through a genome wide association (GWA) study in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). METHODS: The GOLDN GWAS discovery sample consisted of 872 participants within families of European ancestry. Genotypes for 2,543,887 variants were measured or imputed from HapMap. Replication of our top results was performed in the Heredity and Phenotype Intervention (HAPI) Heart Study (n = 843). PPL TG response phenotypes were constructed from plasma TG measured at baseline (fasting, 0 hour), 3.5 and 6 hours after a high-fat meal, using a random coefficient regression model. Association analyses were adjusted for covariates and principal components, as necessary, in a linear mixed model using the kinship matrix; additional models further adjusted for fasting TG were also performed. Meta-analysis of the discovery and replication studies (n = 1715) was performed on the top SNPs from GOLDN. RESULTS: GOLDN revealed 111 suggestive (p < 1E-05) associations, with two SNPs meeting GWA significance level (p < 5E-08). Of the two significant SNPs, rs964184 demonstrated evidence of replication (p = 1.20E 03) in the HAPI Heart Study and in a joint analysis, was GWA significant (p = 1.26E-09). Rs964184 has been associated with fasting lipids (TG and HDL) and is near ZPR1 (formerly ZNF259), close to the APOA1/C3/A4/A5 cluster. This association was attenuated upon additional adjustment for fasting TG. CONCLUSION: This is the first report of a genome-wide significant association with replication for a novel phenotype, namely PPL TG response. Future investigation into response phenotypes is warranted using pathway analyses, or newer genetic technologies such as metabolomics. PMID- 26256469 TI - Bridging waitlist delays with interim buprenorphine treatment: initial feasibility. AB - Despite the effectiveness of agonist maintenance for opioid dependence, individuals can remain on waitlists for months, during which they are at significant risk for morbidity and mortality. Interim dosing, consisting of daily medication without counseling, can reduce these risks. In this pilot study, we examined the initial feasibility of a novel technology-assisted interim buprenorphine treatment for waitlisted opioid-dependent adults. Following buprenorphine induction during Week 1, participants (n=10) visited the clinic at Weeks 2, 4, 6, 8, 10 and 12 to ingest their medication under staff observation, provide a urine specimen and receive their remaining doses via a computerized Med O-Wheel Secure device. They also received daily monitoring via an Interactive Voice Response (IVR) platform, as well as random call-backs for urinalysis and medication adherence checks. The primary outcome was percent of participants negative for illicit opioids at each 2-week visit, with secondary outcomes of past-month drug use, adherence and acceptability. Participants achieved high levels of illicit opioid abstinence, with 90% abstinent at the Week 2 and 4 visits and 60% at Week 12. Significant reductions were observed in self-reported past-month illicit opioid use (p<.001), opioid withdrawal (p<.001), opioid craving (p<.001) and ASI Drug composite score (p=.008). Finally, adherence with buprenorphine administration (99%), daily IVR calls (97%) and random call-backs (82%) was high. Interim buprenorphine treatment shows promise for reducing patient and societal risks during delays to conventional treatment. A larger scale, randomized clinical trial is underway to more rigorously examine the efficacy of this treatment approach. PMID- 26256470 TI - Parental monitoring and family relations: associations with drinking patterns among male and female Mexican students. AB - INTRODUCTION: Parental monitoring and family relations are recognized as protective factors for youth alcohol use. The purpose of this study was to investigate perceived parental monitoring and family relations among subgroups of Mexican youths with different patterns of drinking behaviors and consequences. METHODS: A latent profile analysis (LPA) identified profiles of drinking behavior in a cross-sectional survey of entering first year university students. Multinomial regression examined associations between parental monitoring, family relations and drinking profiles among 22,224 students. RESULTS: Both lower perceived parental monitoring and weaker perceived family relations were associated with heavier drinking profiles among males and females, but more strongly associated with female than male heavier drinking profiles. Being older, having parents with lower education, and not living with parents were also associated with lower parental monitoring and weaker family relations. There was a general trend of lower parental monitoring and weaker family relations as the profiles increased from Non/Infrequent-No Consequences to Excessive-Many Consequences Drinkers. Lower perceived parental monitoring and weaker perceived family relations were more strongly associated with drinking profiles among females than among males. Both the parental monitoring and family relations scales had similar associations with drinking profiles. CONCLUSIONS: Findings suggest that drinking norms and values may contribute to any protective influences of parental monitoring and family relations on Mexican youths' drinking. Research about changes in drinking norms, contextual factors, and youth parent trust would inform the utility of parental monitoring or family relations as protective strategies against alcohol misuse among Mexican and Mexican American youths and also youths from other backgrounds. PMID- 26256471 TI - Elevated oxygen consumption rate in response to acute low-glucose stress: Metformin restores rate to normal level. AB - Cardiovascular disease (CVD) continues to be the leading cause of mortality among all age demographics in the United States, with the highest occurrence in populations aged 65 and older. Glucose levels, particularly hyperglycemia, are associated with the premature onset of age-related diseases including CVD. A major challenge in the treatment of elderly patients with chronically elevated blood glucose is the frequency of hypoglycemic episodes. Molecular mechanisms of hypoglycemia remain unclear, but are associated with premature onset of age related-diseases. Here we report a mitochondrial metabolic profile assessing short-term (up to six hours) and longer-term (12-24h) durations of low-glucose stress. We observed that the anti-diabetic biguanide and mitochondrial complex I inhibitor, metformin, can lower and restore the elevated oxygen consumption rate during shorter-term glucose stress to levels similar to that of cells cultured in normal glucose. This effect appears, in part, to involve activation of the 5' AMP activated protein kinase (AMPK). PMID- 26256472 TI - Pore orientation mediated control of mechanical behavior of scaffolds and its application in cartilage-mimetic scaffold design. AB - Scaffolds with aligned pores are being explored in musculoskeletal tissue engineering due to their inherent structural anisotropy. However, influence of their structure on mechanical behavior remains poorly understood. In this work, we elucidate this dependence using chitosan-gelatin based random and aligned scaffolds. For this, scaffolds with horizontally or vertically aligned pores were fabricated using unidirectional freezing technique. Random, horizontal and vertical scaffolds were characterized for their mechanical behavior under compressive, tensile and shear loading regimes. The results revealed conserved trends in compressive, tensile and shear moduli, with horizontal scaffolds showing the least moduli, vertical showing the highest and random showing intermediate. Further, these scaffolds demonstrated a highly viscoelastic behavior under cyclic compressive loading, with a pore orientation dependent relative energy dissipation. These results established that mechanical behavior of porous scaffolds can be modulated by varying pore orientation alone. This finding paved the way to recreate the structural and consequent mechanical anisotropy of articular cartilage tissue using zonally varied pore orientation in scaffolds. To this end, monolithic multizonal scaffolds were fabricated using a novel sequential unidirectional freezing technique. The superficial zone of this scaffold had horizontally aligned pores while the deep zone consisted of vertically aligned pores, with a transition zone between the two having randomly oriented pores. This depth-dependent pore architecture closely mimicked the collagen alignment of native articular cartilage which translated into similar depth-dependent mechanical anisotropy as well. A facile fabrication technique, biomimetic pore architecture and associated mechanical anisotropy make this multizonal scaffold a promising candidate for cartilage tissue engineering. PMID- 26256473 TI - Investigation of mechanisms of viscoelastic behavior of collagen molecule. AB - Unique mechanical properties of collagen molecule make it one of the most important and abundant proteins in animals. Many tissues such as connective tissues rely on these properties to function properly. In the past decade, molecular dynamics (MD) simulations have been used extensively to study the mechanical behavior of molecules. For collagen, MD simulations were primarily used to determine its elastic properties. In this study, constant force steered MD simulations were used to perform creep tests on collagen molecule segments. The mechanical behavior of the segments, with lengths of approximately 20 (1X), 38 (2X), 74 (4X), and 290 nm (16X), was characterized using a quasi-linear model to describe the observed viscoelastic responses. To investigate the mechanisms of the viscoelastic behavior, hydrogen bonds (H-bonds) rupture/formation time history of the segments were analyzed and it was shown that the formation growth rate of H-bonds in the system is correlated with the creep growth rate of the segment (beta=2.41betaH). In addition, a linear relationship between H-bonds formation growth rate and the length of the segment was quantified. Based on these findings, a general viscoelastic model was developed and verified here, using the smallest segment as a building block, the viscoelastic properties of larger segments could be predicted. In addition, the effect of temperature control methods on the mechanical properties were studied, and it was shown that application of Langevin Dynamics had adverse effect on these properties while the Lowe-Anderson method was shown to be more appropriate for this application. This study provides information that is essential for multi-scale modeling of collagen fibrils using a bottom-up approach. PMID- 26256474 TI - Nickel-Catalyzed Asymmetric Reductive Cross-Coupling between Heteroaryl Iodides and alpha-Chloronitriles. AB - A Ni-catalyzed asymmetric reductive cross-coupling of heteroaryl iodides and alpha-chloronitriles has been developed. This method furnishes enantioenriched alpha,alpha-disubstituted nitriles from simple organohalide building blocks. The reaction tolerates a variety of heterocyclic coupling partners, including pyridines, pyrimidines, quinolines, thiophenes, and piperidines. The reaction proceeds under mild conditions at room temperature and precludes the need to pregenerate organometallic nucleophiles. PMID- 26256475 TI - Systems Analysis of Protein Fatty Acylation in Herpes Simplex Virus-Infected Cells Using Chemical Proteomics. AB - Protein fatty acylation regulates diverse aspects of cellular function and organization and plays a key role in host immune responses to infection. Acylation also modulates the function and localization of virus-encoded proteins. Here, we employ chemical proteomics tools, bio-orthogonal probes, and capture reagents to study myristoylation and palmitoylation during infection with herpes simplex virus (HSV). Using in-gel fluorescence imaging and quantitative mass spectrometry, we demonstrate a generalized reduction in myristoylation of host proteins, whereas palmitoylation of host proteins, including regulators of interferon and tetraspanin family proteins, was selectively repressed. Furthermore, we found that a significant fraction of the viral proteome undergoes palmitoylation; we identified a number of virus membrane glycoproteins, structural proteins, and kinases. Taken together, our results provide broad oversight of protein acylation during HSV infection, a roadmap for similar analysis in other systems, and a resource with which to pursue specific analysis of systems and functions. PMID- 26256476 TI - High-Throughput Multiplexed Peptide-Centric Profiling Illustrates Both Substrate Cleavage Redundancy and Specificity in the MMP Family. AB - Matrix metalloproteinases (MMPs) play incompletely understood roles in health and disease. Knowing the MMP cleavage preferences is essential for a better understanding of the MMP functions and design of selective inhibitors. To elucidate the cleavage preferences of MMPs, we employed a high-throughput multiplexed peptide-centric profiling technology involving the cleavage of 18,583 peptides by 18 proteinases from the main sub-groups of the MMP family. Our results enabled comparison of the MMP substrates on a global scale, leading to the most efficient and selective substrates. The data validated the accuracy of our cleavage prediction software. This software allows us and others to locate, with nearly 100% accuracy, the MMP cleavage sites in the peptide sequences. In addition to increasing our understanding of both the selectivity and the redundancy of the MMP family, our study generated a roadmap for the subsequent MMP structural-functional studies and efficient substrate and inhibitor design. PMID- 26256478 TI - Design and Synthesis of Activity-Based Probes and Inhibitors for Bleomycin Hydrolase. AB - Bleomycin hydrolase (BLMH) is a neutral cysteine aminopeptidase that has been ascribed roles in many physiological and pathological processes, yet its primary biological function remains enigmatic. In this work, we describe the results of screening of a library of fluorogenic substrates to identify non-natural amino acids that are optimally recognized by BLMH. This screen identified several substrates with kcat/KM values that are substantially improved over the previously reported fluorogenic substrates for this enzyme. The substrate sequences were used to design activity-based probes that showed potent labeling of recombinant BLMH as well as endogenously expressed BLMH in cell extracts, and in intact cells. Importantly, we identify potent BLMH inhibitors that are able to fully inhibit endogenous BLMH activity in intact cells. These probes and inhibitors will be valuable new reagents to study BLMH function in cellular and animal models of human diseases where BLMH is likely to be involved. PMID- 26256477 TI - Chemical Lectinology: Tools for Probing the Ligands and Dynamics of Mammalian Lectins In Vivo. AB - The importance and complexity associated with the totality of glycan structures, i.e. the glycome, has garnered significant attention from chemists and biologists alike. However, what is lacking from this biochemical picture is how cells, tissues, and organisms interpret glycan patterns and translate this information into appropriate responses. Lectins, glycan-binding proteins, are thought to bridge this gap by decoding the glycome and dictating cell fate based on the underlying chemical identities and properties of the glycome. Yet, our understanding of the in vivo ligands and function for most lectins is still incomplete. This review focuses on recent advances in chemical tools to study the specificity and dynamics of mammalian lectins in live cells. A picture emerges of lectin function that is highly sensitive to its organization, which in turn drastically shapes immunity and cancer progression. We hope this review will inspire biologists to make use of these new techniques and stimulate chemists to continue developing innovative approaches to probe lectin biology in vivo. PMID- 26256479 TI - Repurposing Hsp104 to Antagonize Seminal Amyloid and Counter HIV Infection. AB - Naturally occurring proteolytic fragments of prostatic acid phosphatase (PAP248 286 and PAP85-120) and semenogelins (SEM1 and SEM2) form amyloid fibrils in seminal fluid, which capture HIV virions and promote infection. For example, PAP248-286 fibrils, termed SEVI (semen-derived enhancer of viral infection), can potentiate HIV infection by several orders of magnitude. Here, we design three disruptive technologies to rapidly antagonize seminal amyloid by repurposing Hsp104, an amyloid-remodeling nanomachine from yeast. First, Hsp104 and an enhanced engineered variant, Hsp104(A503V), directly remodel SEVI and PAP85-120 fibrils into non-amyloid forms. Second, we elucidate catalytically inactive Hsp104 scaffolds that do not remodel amyloid structure, but cluster SEVI, PAP85 120, and SEM1(45-107) fibrils into larger assemblies. Third, we modify Hsp104 to interact with the chambered protease ClpP, which enables coupled remodeling and degradation to irreversibly clear SEVI and PAP85-120 fibrils. Each strategy diminished the ability of seminal amyloid to promote HIV infection, and could have therapeutic utility. PMID- 26256480 TI - Highly accurate thermal flow microsensor for continuous and quantitative measurement of cerebral blood flow. AB - Cerebral blood flow (CBF) plays a critical role in the exchange of nutrients and metabolites at the capillary level and is tightly regulated to meet the metabolic demands of the brain. After major brain injuries, CBF normally decreases and supporting the injured brain with adequate CBF is a mainstay of therapy after traumatic brain injury. Quantitative and localized measurement of CBF is therefore critically important for evaluation of treatment efficacy and also for understanding of cerebral pathophysiology. We present here an improved thermal flow microsensor and its operation which provides higher accuracy compared to existing devices. The flow microsensor consists of three components, two stacked up thin film resistive elements serving as composite heater/temperature sensor and one remote resistive element for environmental temperature compensation. It operates in constant-temperature mode (~2 degrees C above the medium temperature) providing 20 ms temporal resolution. Compared to previous thermal flow microsensor based on self-heating and self-sensing design, the sensor presented provides at least two-fold improvement in accuracy in the range from 0 to 200 ml/100 g/min. This is mainly achieved by using the stacked-up structure, where the heating and sensing are separated to improve the temperature measurement accuracy by minimization of errors introduced by self-heating. PMID- 26256482 TI - Immunohistochemical biomarkers and FDG uptake on PET/CT in head and neck squamous cell carcinoma. AB - BACKGROUND: There is an exciting complementarity between the spatial resolution provided by molecular imaging of a single, often unspecific, biomarker on one hand and the more detailed biological profile achievable from a diagnostic biopsy using a panel of immunohistochemical (IHC) markers on the other. A number of previous studies have shown a relationship between glucose transport protein expression and 18F-Fludeoxyglucose (FDG) PET uptake. Here, FDG uptake is analyzed in relation to expression of a selected panel of IHC cancer biomarkers in head and neck squamous cell carcinomas (HNSCC). MATERIAL AND METHODS: IHC staining for Bcl-2, beta-tubulin-1 and 2, p53, EGFR, Ki-67, glutathione-S-transferase-pi and p16 was performed on formalin-fixed paraffin embedded diagnostic biopsies from 102 HNSCC cases treated at Rigshospitalet during 2005-2009. The proportion of positive cells was used for analyses, except p16, which was scored according to EORTC guidelines. In all cases, maximal FDG standardized uptake value (SUV) metrics were extracted for the primary tumor, TSUVmax. Univariate linear regression and multiple linear regression of TSUVmax versus IHC markers were performed. RESULTS: In univariate analyses, TSUVmax showed negative associations with Bcl-2 (p = 0.002) and p16 (p = 0.005) indices and positive association with beta-tubulin-1 index (p = 0.003). On multivariate analysis, TSUVmax remained associated with beta-tubulin-1 (p = 0.009), Bcl-2 (p = 0.03) and p16 (p = 0.03). All correlations had r-squared < 0.3. CONCLUSION: Statistically significant correlations were observed between the expression of IHC biomarkers and maximum FDG uptake in the primary tumor. PMID- 26256481 TI - A multilayered microfluidic blood vessel-like structure. AB - There is an immense need for tissue engineered blood vessels. However, current tissue engineering approaches still lack the ability to build native blood vessel like perfusable structures with multi-layered vascular walls. This paper demonstrated a new method to fabricate tri-layer biomimetic blood vessel-like structures on a microfluidic platform using photocrosslinkable gelatin hydrogel. The presented method enables fabrication of physiological blood vessel-like structures with mono-, bi- or tri-layer vascular walls. The diameter of the vessels, the total thickness of the vessel wall and the thickness of each individual layer of the wall were independently controlled. The developed fabrication process is a simple and rapid method, allowing the physical fabrication of the vascular structure in minutes, and the formation of a vascular endothelial cell layer inside the vessels in 3-5 days. The fabricated vascular constructs can potentially be used in numerous applications including drug screening, development of in vitro models for cardiovascular diseases and/or cancer metastasis, and study of vascular biology and mechanobiology. PMID- 26256483 TI - Relationship between leukocytes recruitment and risk of rebleeding in patients with peptic ulcers. AB - AIM: The aim of this study was to assess the impact of leukocytes reaction on rebleeding development among patients with peptic ulcers. METHODS: This was a single-center cohort study enrolling 232 patients with a diagnosis of gastroduodenal ulcer bleeding. The end point was the in-hospital rebleeding rate during the three days after admission. The impact of clinical, demographic, endoscopic and laboratory data at the time of admission, as well as macrophages (CD68) and neutrophils count in ulcer margin, on bleeding outcome was assessed. In addition, impact of the leukocytes on the platelets aggregation induced with ADP (5MUM) and collagen (1MUM) was measured in vitro. RESULTS: Acute ulcer bleeding was accompanied with an acute inflammatory response to damage and hemorrhage. Despite the increase of neutrophil count (P=0.031) in peripheral blood of bleeders, there were not significant influence of this parameter on the outcome. It was shown that the most significant predicting factors were an increased neutrophils (OR 1.4; 95% CI 1.1-1.8) and macrophages count in the ulcer margin (OR 3.5; 95% CI 1.9-4.87); an endoscopically diagnosed active bleeding (OR 3.0; 95% CI 1.4-6.3); an enhanced level of plasma fibrinogen (OR 1.04; 95% CI 1.0 1.08). Co-incubation of platelets with leukocytes significantly decreased the collagen induced aggregation (P=0.008) that could indicate either alteration of mechanisms of platelets adhesion, or inhibition of stabilization phase of thrombogenesis. CONCLUSION: The severity of the local acute inflammatory reaction promotes progressive tissue damage of ulcer margin, and increases the risk of rebleeding. PMID- 26256484 TI - A novel therapeutic target of spontaneous bacterial peritonitis: skewing M2 polarization through vitamin D-VDR-IL-37 pathway. PMID- 26256485 TI - Benzodiazepines - Effects on Human Performance and Behavior. AB - There exist a large number of drugs belonging to the benzodiazepine family. These include the 1,4-benzodiazepines such as diazepam, temazepam and oxazepam, the often more potent diazolo- and triazolo-groups represented by alprazolam, midazolam, triazolam etc. These drugs represent a large range of potencies from submilligram doses to over 100 mg and a range of polarities. Consequently, blood or plasma concentrations associated with prescribed use range from sub-nanogram per mL to near-microgram per mL. Their medical use varies, but they are predominantly used as hypnotics and sedatives. Some members are also used in the treatment of post-traumatic stress and obsessive-compulsive disorders, alcohol withdrawal, muscle spasm, and seizures. Recreationally, drug users favor these drugs to reduce the symptoms of withdrawal and unpleasant effects of heroin and cocaine. They are also commonly used as "date-rape" drugs to render a victim incapable of resisting an attack. Benzodiazepines elicit a large number of physiological and psychological responses in humans that often can lead to significant behavioral changes and adverse effects on skills required for safe driving. These include reduced lane control, increased reaction times, reduced hand-eye coordination and cognitive impairment. Impairment can exceed that seen with 0.05 g% ethanol. In high doses benzodiazepines can cause persons to exhibit classical features of CNS-depressant drugs such as nystagmus, ataxia, slurred speech, and impaired divided attention skills. As one would expect with hypnotics and sedatives, any sleep deprivation, or situations involving monotonous driving can lead to a reduced ability to concentrate and maintain vigilance. Adverse effects on REM and NREM sleep patterns will exacerbate fatigue-related components to driving. Persons with sleep abnormalities, e.g., sleep apnea, may be more likely to be affected by benzodiazepines than those with normal sleep patterns. Ethanol and narcotic analgesics also affect sleep patterns and may compound any CNS-depressant effects associated with the use of benzodiazepines. PMID- 26256486 TI - Cannabis (Marijuana) - Effects on Human Performance and Behavior. AB - Cannabis is one of the oldest and most commonly abused drugs in the world. Recently, tremendous advances have been made in our understanding of the endogenous cannabinoid system with the identification of cannabinoid receptors, cannabinoid receptor antagonists, endogenous neurotransmitters, metabolic enzymes, and reuptake mechanisms. These advances have helped us to elucidate the mechanisms of action of cannabis and the side effects and toxicities associated with its use. In addition, potential therapeutic applications are being investigated for the use of smoked cannabis and synthetic THC (dronabinol). Most workplace, military, and criminal justice positive urine drug tests are due to the use of cannabis. In addition, alternative matrices, including saliva, sweat, and hair, are being utilized for monitoring cannabis use in treatment, employment, and criminal justice settings. Experimental laboratory studies have identified cognitive, physiological, and psychomotor effects following cannabis. Epidemiological studies reveal that cannabis is the most common illicit drug world-wide in impaired drivers, and in motor vehicle injuries and fatalities. Driving simulator studies also indicate performance impairment following cannabis use; however, the results of open- and closed-road driving studies and of culpability studies do not consistently document increased driving risk. Clearly a combination of ethanol and cannabis use significantly increases risks. This article reviews the pharmacokinetics and pharmacodynamics of cannabis and places special emphasis on the effects of cannabis on complex tasks such as driving and flying. PMID- 26256487 TI - Cocaine - Effects on Human Performance and Behavior. AB - A brief history of cocaine is provided followed by an overview of the pharmacology of cocaine. In addition to the mechanism of action, the effects of cocaine withdrawal and its effects in combination with ethanol are discussed. Special emphasis is placed on the metabolism of cocaine and the interpretation of the concentration of cocaine and metabolites detected in various matrices. Consideration is given to stability of the drug, pathology, postmortem observations, passive and unknowing ingestion, and dermal exposure. A brief overview of analytical methodology is also presented. Finally, the effects of cocaine on driving are examined. PMID- 26256488 TI - gamma-Hydroxybutyrate (GHB) - Effects on Human Performance and Behavior. AB - gamma-Hydroxybutyrate (GHB) is a powerful central nervous system (CNS) depressant which has had a history of limited therapeutic use and, more recently, potential for abuse. GHB is a naturally occurring compound present in mammalian CNS and peripheral tissues, and a minor metabolite and precursor of gamma-amino butyric acid. GHB is also an emerging recreational drug and has limited therapeutic potential. It is now a federally controlled substance. Since the substances gamma butyrolactone and 1,4-butanediol rapidly convert to GHB in vivo, they are abused as metabolic precursor drugs for GHB and are available in a wide variety of forms. GHB alters dopaminergic activity in the CNS, and its effects are primarily those of a CNS depressant. Following low doses, euphoria, relaxation, reduced inhibitions and sedation can be observed, while vomiting, sweating, severe respiratory depression, and unconsciousness are common with GHB intoxication. Tolerance to the effects of GHB develops with chronic use, and physical and psychological addiction can follow. This monograph reviews the chemistry of GHB and its precursor drugs, their reported medicinal and recreational uses, pharmacology, pharmacokinetics, metabolism, analytical methodology, and interpretation issues such as postmortem endogenous concentrations and specimen storage conditions. The manuscript concludes with a discussion of the effects GHB may have on human performance. Given the ability of GHB to induce sleep and unconsciousness, recreational use of GHB and its precursor drugs GBL and 1,4 butanediol has the potential of causing impairment in psychomotor and cognitive skills. PMID- 26256489 TI - Katamine - Effects on Human Performance and Behavior. AB - Ketamine is a rapid-acting anesthetic commonly used during surgical procedures in both animals and humans, as an experimental drug in the treatment of chronic pain, and as a probe for the study of the cause of schizophrenia. When used medically as an anesthetic it is administered as an intravenous (IV) solution, but when diverted to the illicit market it can be injected, snorted, smoked, or consumed in drinks. Ketamine produces effects similar in some respects to phencyclidine (PCP) and lysergic acid (LSD), but of shorter duration. Psychedelic effects are produced quickly by low doses of the drug, although larger doses are frequently used in an attempt to produce "near-death" experiences. Convulsions and death can be caused by higher doses, although most deaths in which ketamine is detected are the result of poly-drug use or trauma. Reports of ketamine use at rave parties attended by young adults appear to be on the rise. The effects from ketamine last from 1-5 hours, and ketamine can be detected in the urine for a period of 1-2 days following use. PMID- 26256490 TI - Methamphetamine - Effects on Human Performance and Behavior. AB - Methamphetamine is a popular recreational drug that has also had some historical use as a therapeutic agent. Its effect profile is complex, with stimulant, alerting effects during acute low-dose administration, progressively more disorienting effects on cognition, reasoning, and psychomotor ability with increased dosing and duration of use, and a depressant-like profile during withdrawal, often compounded by delusions and psychotic episodes, especially after high-dose or chronic use. This manuscript reviews the synthetic, structural, and analytical chemistry of the drug; the pharmacology of its central and peripheral effects; its pharmacokinetics following various routes of administration and dosage regimens; and its pharmacodynamics in both acute and chronic administration and therapeutic and recreational doses, noting in particular its effects on judgment, decision making, risk-taking, cognition and psychomotor performance, and violence. Finally, the review considers the issue of how these various effects can impact driving ability and can contribute to impairment. From the material reviewed it is concluded that the use of methamphetamine in anything other than low-dose, therapeutic administration with medical oversight raises the likelihood of some impairment of performance in complex psychomotor tasks such as driving. PMID- 26256491 TI - A canine case with cystic meningioma showing miraculous reduction of the cystic lesion. AB - A 12-year-old spayed female Labrador retriever was presented with forebrain signs. Brain MRI revealed a huge cystic lesion with the thickened falx in the frontal region. The brain parenchyma surrounding the lesion showed significant signs of a mass effect and also increased intracranial pressure. However, the dog suddenly became lucid after about two weeks, and an MRI scan one month after the initial study revealed a dramatically shrunken cystic lesion. The dog survived for over a year until it was euthanized for other reasons, and the brain lesion was diagnosed as a cystic meningioma histologically. To the authors' knowledge, this is the first report that described the reduction of the cystic lesion of a cystic meningioma in dogs. PMID- 26256492 TI - Seroprevalence of antibody to NcSAG1 antigen of Neospora caninum in cattle from Western Java, Indonesia. AB - Neospora caninum can cause fetal abortion and neonatal mortality in cattle, and is a cause of economic concern worldwide. This study aimed to determine the prevalence of Neospora caninum-specific antibodies in cattle from Western Java, Indonesia. Serum samples from 991 cattle from 21 locations were tested for antibodies to N. caninum by using an enzyme-linked immunosorbent assay (ELISA) on the basis of recombinant NcSAG1. The overall seroprevalence was 16.6%, ranging from 0 to 87.5% in the sampled locations. The results of this study indicate latent infection rates of sampled animals were different in each location. Further studies are necessary to elucidate the relationship between N. caninum infection and abortion in cattle, and to identify risk factors for infection in high-prevalence environments. PMID- 26256493 TI - Relationship Between the Electroglottographic Signal and Vocal Fold Contact Area. AB - OBJECTIVE: Electroglottography (EGG) is a widely used noninvasive method that purports to measure changes in relative vocal fold contact area (VFCA) during phonation. Despite its broad application, the putative direct relation between the EGG waveform and VFCA has to date only been formally tested in a single study, suggesting an approximately linear relationship. However, in that study, flow-induced vocal fold (VF) vibration was not investigated. A rigorous empirical evaluation of EGG as a measure of VFCA under proper physiological conditions is therefore still needed. METHODS/DESIGN: Three red deer larynges were phonated in an excised hemilarynx preparation using a conducting glass plate. The time varying contact between the VF and the glass plate was assessed by high-speed video recordings at 6000 fps, synchronized to the EGG signal. RESULTS: The average differences between the normalized [0, 1] VFCA and EGG waveforms for the three larynges were 0.180 (+/-0.156), 0.075 (+/-0.115), and 0.168 (+/-0.184) in the contacting phase and 0.159 (+/-0.112), -0.003 (+/-0.029), and 0.004 (+/ 0.032) in the decontacting phase. DISCUSSIONS AND CONCLUSIONS: Overall, there was a better agreement between VFCA and the EGG waveform in the decontacting phase than in the contacting phase. Disagreements may be caused by nonuniform tissue conductance properties, electrode placement, and electroglottograph hardware circuitry. Pending further research, the EGG waveform may be a reasonable first approximation to change in medial contact area between the VFs during phonation. However, any quantitative and statistical data derived from EGG should be interpreted cautiously, allowing for potential deviations from true VFCA. PMID- 26256494 TI - Visualization and Estimation of Vibratory Disturbance in Vocal Fold Scar Using High-Speed Digital Imaging. AB - OBJECTIVE: To explore the method to visualize and quantify the abnormality of vocal fold vibration in vocal fold scar (VFS) using high-speed digital imaging (HSDI). METHODS: HSDI was performed on 12 patients (2 men and 10 women) with VFS and 46 vocally healthy subjects (17 men and 29 women), and the obtained data were quantitatively evaluated by frame-by-frame analysis, laryngotopography (LTG), single-line and multiline kymography, and glottal area waveform. RESULTS: Visualization of a scarred area was feasible in 75% of VFS in the present study using LTG. Quantitative HSDI analysis revealed that VFS had poorer glottal closure (eg, larger open quotients, larger minimal glottal area), reduced vibration in a scarred area (eg, smaller mucosal wave magnitude, mucosal wave persistence, lateral peak index), and greater asymmetry (eg, amplitude difference, mucosal wave magnitude difference, lateral phase difference) than the control group. Correlation study revealed moderate correlations between HSDI derived parameters and conventional acoustic or aerodynamic parameters (eg, period perturbation quotient). CONCLUSIONS: HSDI is considered to be useful in the diagnosis of VFS, visualization of a scarred area, and quantification of vibratory abnormality. PMID- 26256495 TI - [Low back pain: when and what to do]. AB - The low back pain has become one of the greatest public health problems worldwide. The author based on the current international standards summarizes the knowledge necessary for every day treatment of low back pain. In acute low back pain the author underlines the necessity of the rapid, accurate diagnosis and separation for specific and non-specific low back pain. In specific acute low back pain the treatment should focus on to eliminate the root causes. In non specific cases pain killing treatment and early active mobilization is the choice for the therapeutic process. Beside analgesia, the primary goal of the treatment is to prevent becoming chronic the symptomatology. Objectives of the management of chronic low back pain are effective pain reduction, continuous maintainance of physical activity, prevention of permanent disability, and restoration of working ability. Analgesics, non steroid anti-inflammatory drugs, and muscle relaxants reduce pain, while multidisciplinary management programs, personalized and guided physiotherapy, cognitive behavioral therapy, as well as short training programs will help to restore function. Surgical treatment is only indicated in degenerative cases and only after the failure of conservative therapy. PMID- 26256496 TI - [Psychological interventions following trauma to prevent posttraumatic stress disorder. A systematic review of the literature]. AB - INTRODUCTION: Because of the high prevalence of exposure to traumatic events and its negative consequences on mental health, the importance of effective interventions to prevent posttraumatic stress disorder has been emphasized. AIM: The authors wanted to evaluate the current status of evidence regarding early psychological interventions after traumatization. METHOD: A search was conducted in ProQuest PILOTS, PubMed, and Web of Science for early psychological interventions that were published between 2005 and 2015. RESULTS: Twenty-one trials were identified, of which 6 presented immediate interventions (within 72 hours) and the rest early interventions within the first month. Based on these research findings immediate interventions are not effective, whilst multi-session cognitive behavior therapies could be effective in symptom reduction. CONCLUSIONS: Multi-session cognitive behavior therapy is preferred over immediate one session interventions especially over debriefing. A natural decline of symptoms was observed among controls and, therefore, targeted interventions are recommended only for people with higher risk for developing subsequent posttraumatic stress disorder. PMID- 26256497 TI - [Use of high-fidelity patient simulators for the assessment of students' performance]. AB - INTRODUCTION: The authors started to use high-fidelity simulators at Semmelweis University, Faculty of Health Sciences in September, 2007. AIM: The aim of this study was to evaluate the students' performance in order to determine their knowledge after each simulation course. METHOD: The Creighton Simulation Evaluation Instrument (C-SEI) was used to evaluate midwifery students' performance during examinations. 67 midwifery students were evaluated after the "Clinical simulation" course and 58 midwifery students after the "Case studies in simulation" course. RESULTS: The average total scores were significantly higher than the desired level of 75 (p<0.01); after the "Clinical simulation" 88.8+/ 9,14, and after the "Case studies in simulation" courses 86.6+/-14.87. Among subscales the lowest average total score was found in critical thinking in each of the course. Statistically significant correlation was found between the results of "General nursing care" and the results of "Case studies in simulation" courses (r = 0.34; p<0.01). CONCLUSIONS: The use of high-fidelity simulators with valid tools simultaneously might be a suitable method for students' evaluation. PMID- 26256498 TI - [Correlations between skin autofluorescence and conventional glycemic markers in patients with diabetes]. AB - INTRODUCTION: Skin autofluorescence has a well-known significance for screening diabetes and early diagnosis of vascular complications. It predicts cardiovascular events better than hemoglobin A1c, hence skin autofluorescence is a marker of cumulative tissue glycemic load whereas hemoglobin A1c reflects changes occurring in the previous 6-8 weeks. AIM: The aim of the authors was analyze the relationship between skin autofluorescence and conventional glycemic markers in patients with diabetes. METHOD: Skin autofluorescence measurements were performed in 2010 in 18 patients (10 men and 8 women with normal glomerular filtration rate; age, 61.4+/-13.8 years) with long term follow-up (2624 months, 476 laboratory results). Relationships between skin autofluorescence values and fasting blood glucose, hemoglobin A1c levels and metabolic parameters obtained before and after skin autofluorescence measurements were analysed using Spearman rank test. RESULTS: The average skin autofluorescence value was 2.88+/-0.65 arbitrary units. There were no significant correlations between skin autofluorescence and hemoglobin A1c levels obtained before (7.84+/-1.08%, p = 0.07) and after the skin autofluorescence measurements (7.45+/-1.18%, p = 0.71). Skin autofluorescence values also failed to show relationship with fasting blood glucose obtained before (p = 0.09) and after (p = 0.29) the skin autofluorescence measurements. CONCLUSIONS: In patients with diabetes skin autofluorescence may provide novel information about glycemic burden. Skin autofluorescence values (which may presumably provide a more accurate estimation of the cardiovascular risk) do not correlate with hemoglobin A1c and fasting blood glucose. PMID- 26256499 TI - [Isolated hypospadias in 5 brothers]. AB - The healthy couple had five sons with hypospadias (glandular 1, coronal 4) without other child. Similar familial cluster has not reported in the sons of European parents without consanguinity. Mild form androgen insensitivity syndrome was expected in these 5 boys because of the X-linked androgen receptor gene, however, sequencing of the entire coding region (exons 1-8) and all intron-exon boundaries of the androgen receptor gene did not reveal abnormality and the CAG repeat was found in the normal range (21 repeats). This extreme familial cluster may help us to elucidate gene polymorphisms in the polygenic background of the multifactorial origin of isolated hypospadias. Therefore, the authors collaborate with a genetic institute in Pittsburg, USA to perform whole genome sequencing in these probands and their parents. PMID- 26256500 TI - Administration of Hwang-Ryun-Haedok-tang, a Herbal Complex, for Patients With Abdominal Obesity: A Case Series. AB - Herbal medicines have received attention as antiabdominal obesity agents. We present a series of 13 cases that demonstrate the positive effect of the herbal complex Hwang-Ryun-Haedok-Tang (HRHT; Tsumura, Tokyo, Japan) on weight and abdominal fat control in patients with abdominal obesity. We treated 13 patients with abdominal obesity treated for 54.46 +/- 18.07 days with 5.0 g of HRHT daily. To evaluate the treatment, the morphometric (i.e., waist circumstance, weight, body fat) and biochemical parameters were measured once monthly. After HRHT therapy, the waist circumstance decreased from 91.96 +/- 7.99 cm to 87.12 +/- 8.09 cm (paired t test, P < .001) and the weight decreased from 78.09 +/- 14.35 kg (average +/- standard deviation) to 75.72 +/- 14.60 kg (paired t test, P < .001). All 13 (100%) patients had low waist circumstances after treatment. Overall, 12 (92.3%) of the 13 patients had a lower weight and body mass index. In the present study, we showed the clinical effects of HRHT on waist circumstance, weight, body mass index, and body fat in patients with abdominal obesity. Further clinical studies investigating the effects of HRHT are needed. PMID- 26256501 TI - International Society for Plasmid Biology. PMID- 26256502 TI - Introduction: Surface Histories. PMID- 26256503 TI - Dust Plate, Retina, Photograph: Imaging on Experimental Surfaces in Early Nineteenth-Century Physics. AB - This article explores the entangled histories of three imaging techniques in early nineteenth-century British physical science, techniques in which a dynamic event (such as a sound vibration or an electric spark) was made to leave behind a fixed trace on a sensitive surface. Three categories of "sensitive surface" are examined in turn: first, a metal plate covered in fine dust; second, the retina of the human eye; and finally, a surface covered with a light-sensitive chemical emulsion (a photographic plate). For physicists Michael Faraday and Charles Wheatstone, and photographic pioneer William Henry Fox Talbot, transient phenomena could be studied through careful observation and manipulation of the patterns wrought on these different surfaces, and through an understanding of how the imaging process unfolded through time. This exposes the often-ignored materiality and temporality of epistemic practices around nineteenth-century scientific images said to be "drawn by nature." PMID- 26256504 TI - Leviathan and the Myograph: Hermann Helmholtz's "Second Note" on the Propagation Speed of Nervous Stimulations. AB - In the winter of 1849-1850 in Konigsberg, German physiologist Hermann von Helmholtz (1821-1894) conducted pioneering measurements concerning the propagation speed of stimulations in the living nerve. While recent historians of science have paid considerable attention to Helmholtz's uses of the graphic method, in particular his construction of an instrument called "myographion," this paper draws attention to the inscription surfaces that he used in effective ways for capturing and transmitting his findings. Against the background of recent archival findings, I show that Helmholtz used isinglass copies of his graphical recordings in order to communicate the basic principle of previous measurements to the academic public. As the correspondence with his Berlin-based friend and colleague Emil du Bois-Reymond (1818-1896) and the subsequent development of the myographion make clear, these curves were not meant as measurements but functioned as demonstrations. In other words, Helmholtz's curves did provide "images of precision" (Olesko and Holmes 1993) - but they were not precise images. PMID- 26256505 TI - From Topos to Oikos: The Standardization of Glass Containers as Epistemic Boundaries in Modern Laboratory Research (1850-1900). AB - Glass vessels such as flasks and test tubes play an ambiguous role in the historiography of modern laboratory research. In spite of the strong focus on the role of materiality in the last decades, the scientific glass vessel - while being symbolically omnipresent - has remained curiously neglected in regard to its materiality. The popular image or topos of the transparent, neutral, and quasi-immaterial glass container obstructs the view of the physico-chemical functionality of this constitutive inner boundary in modern laboratory environments and its material historicity. In order to understand how glass vessels were able to provide a stable epistemic containment of spatially enclosed experimental phenomena in the new laboratory ecologies emerging in the nineteenth and early twentieth century, I will focus on the history of the material standardization of laboratory glassware. I will follow the rise of a new awareness for measurement errors due to the chemical agency of experimental glass vessels, then I will sketch the emergence of a whole techno-scientific infrastructure for the improvement of glass container quality in late nineteenth century Germany. In the last part of my argument, I will return to the laboratory by looking at the implementation of this glass reform that created a new oikos for the inner experimental milieus of modern laboratory research. PMID- 26256506 TI - Shaping Vulnerable Bodies at the Thin Boundary between Environment and Organism: Skin, DNA Repair, and a Genealogy of DNA Care Strategies. AB - This paper brings together the history of risk and the history of DNA repair, a biological phenomenon that emerged as a research field in between molecular biology, genetics, and radiation research in the 1960s. The case of xeroderma pigmentosum (XP), an inherited hypersensitivity to UV light and, hence, a disposition to skin cancer will be the starting point to argue that, in the 1970s and 1980s, DNA repair became entangled in the creation of new models of the human body at risk - what is here conceptually referred to as the vulnerability aspect of body history - and new attempts at cancer prevention and enhancement of the body associated with the new flourishing research areas of antimutagenesis and anticarcinogenesis. The aim will be to demonstrate that DNA repair created special attempts at disease prevention: molecular enhancement, seeking to identify means to increase the self-repair abilities of the body at the molecular level. Prevention in this sense meant enhancing the body's ability to cope with the environmental hazards of an already toxic world. This strategy has recently been adopted by the beauty industry, which introduced DNA care as a new target for skin care research and anti-aging formulas. PMID- 26256507 TI - Reading Communities and Hippocratism in Hellenistic Medicine. AB - The sect of ancient Greek physicians who believed that medical knowledge came from personal experience also read the Hippocratic Corpus intensively. While previous scholarship has concentrated on the contributions of individual physicians to ancient scholarship on Hippocrates, this article seeks to identify those characteristics of Empiricist reading methodology that drove an entire medical community to credit Hippocrates with medical authority. To explain why these physicians appealed to Hippocrates' authority, I deploy surviving testimonia and fragments to describe the skills, practices, and ideologies of the reading community of ancient Empiricist physicians over the one-hundred year period 175 to 75 BCE. The Empiricist conception of testimony taken on trust operative within that reading community elided the modern distinction between personal and institutional targets of trust by treating Hippocratic writings as revelatory of the moral character of Hippocrates as an author. Hippocrates' moral character as an honest witness who accurately observed empirical phenomena aligned with the epistemic virtues of an empirical medical community who believed that medical knowledge came from personal experience. So I argue that Empiricist reading culture constructed a moral authority of honesty and accuracy from Hippocratic writings, enlarged the personal authority of Hippocrates among medical readers, and contributed to the development of Hippocratism. PMID- 26256508 TI - The Emergence of Genetic Counseling in Sweden: Examples from Eugenics and Medical Genetics. AB - This paper examines the intertwined relations between eugenics and medical genetics from a Swedish perspective in the 1940s and 1950s. The Swedish case shows that a rudimentary form of genetic counseling emerged within eugenic practices in the applications of the Swedish Sterilization Act of 1941, here analyzed from the phenomenon of "heredophobia" (arftlighetsskrack). At the same time genetic counseling also existed outside eugenic practices, within the discipline of medical genetics. The paper argues that a demand for genetic counseling increased in the 1940s and 1950s in response to a sense of reproductive responsibility engendered by earlier eugenic discourse. The paper also questions the claim made by theoreticians of biopolitics that biological citizens have emerged only during the last decades, especially in neoliberal societies. From the Swedish case it is possible to argue that this had already happened earlier in relation to the proliferation of various aspects of eugenics to the public. PMID- 26256509 TI - Engaging therapeutic citizenship and clientship: Untangling the reasons for therapeutic pacifism among people living with HIV in urban Zambia. AB - This article explores the reasons for therapeutic pacifism among people living with HIV (PLHIVs) in urban Zambia. It contributes to a growing ethnography on global health, biosociality, and patient-provider dynamics. Therapeutic citizenship is a biopolitical citizenship that includes claims and ethical projects that emerge from techniques to control and manage bodies. In some contexts, therapeutic citizenship has included activism and claims-making against local, national, and international power brokers. This article investigates therapeutic citizenship in the specific context of impoverished urban Zambian compounds, sites of food insecurity, unemployment, and political exclusion, as well as targets for donor, NGO, and faith-based organisation projects and PLHIV support group proliferation. The article utilises data from participant observations at two Lusaka AIDS clinics, interviews, and focused discussions with support groups of PLHIVs. It argues that PLHIVs continuously negotiate subjectivities related to kinship, clientship, religious belief, and political citizenship in processes that complicate therapeutic citizenship. Rather than fostering participation in PLHIV support groups or challenging 'politics as usual' through activist claims-making to institutions of biopower, these processes lead to therapeutic pacifism. PMID- 26256510 TI - Carrier effects on tertiary nitrifying moving bed biofilm reactor: An examination of performance, biofilm and biologically produced solids. AB - Increasingly stricter ammonia and nitrogen release regulations with respect to wastewater effluents are creating a need for tertiary treatment systems. The moving bed biofilm reactor (MBBR) is being considered as an upgrade option for an increasing number of wastewater treatment facilities due to its small footprint and ease of operation. Despite the MBBRs creation as a system to remove nitrogen, recent research on MBBR systems showing that the system's performance is directly related to carrier surface area and is irrespective of carrier shape and type has been performed exclusively on chemical oxygen demand (COD) removal systems. Furthermore, the influence of carrier type on the solids produced by MBBR systems has also been exclusively studied for COD removal systems. This work investigates the effects of three specific carrier types on ammonia removal rates, biofilm morphology, along with solids production and settleability of tertiary nitrifying MBBR systems. The study concludes that carrier type has no significant effect on tertiary nitrifying MBBR system performance under steady, moderate loading conditions. The research does however highlight the propensity of greater surface area to volume carriers to become clogged under high loading conditions and that the high surface area carriers investigated in this study required longer adjustment periods to changes in loading after becoming clogged. PMID- 26256511 TI - Legonaridin, a new member of linaridin RiPP from a Ghanaian Streptomyces isolate. AB - Linaridins are rare linear ribosomally-synthesized and post-translationally modified peptides (RiPPs) and only two, cypemycin and SGR-1832, in this family have been identified so far. Legonaridin 1 has been discovered as a new member of linaridins through chemical isolation, peptidogenomics, comprehensive 1- and 2-D NMR and advanced Marfey's analyses from the soil bacterium Streptomyces sp. CT34, an isolate collected from Legon, Ghana. Bioinformatics analysis of the gene cluster suggested that the biosynthesis of legonaridin 1 is different from those of cypemycin and SGR-1832. Consistent with bioinformatics and peptidogenomics analyses, 1 has a total of nine post-modifications, 8 dehydrobutyrine residues and a N,N-dimethylated N-terminus with a carboxylic acid at the C-terminus. Legonaridin 1 is structurally different from the two known linaridins comprising a new subfamily. This is the first time that NMR spectroscopy is used to establish the 2-D structure of a linaridin RiPP. PMID- 26256512 TI - Optical Signatures of Quantum Delocalization over Extended Domains in Photosynthetic Membranes. AB - The prospect of coherent dynamics and excitonic delocalization across several light-harvesting structures in photosynthetic membranes is of considerable interest, but challenging to explore experimentally. Here we demonstrate theoretically that the excitonic delocalization across extended domains involving several light-harvesting complexes can lead to unambiguous signatures in the optical response, specifically, linear absorption spectra. We characterize, under experimentally established conditions of molecular assembly and protein-induced inhomogeneities, the optical absorption in these arrays from polarized and unpolarized excitation, and demonstrate that it can be used as a diagnostic tool to determine the resonance coupling between iso-energetic light-harvesting structures. The knowledge of these couplings would then provide further insight into the dynamical properties of transfer, such as facilitating the accurate determination of Forster rates. PMID- 26256513 TI - Value investing is the best model for selecting plastic surgery trainees. PMID- 26256514 TI - Key factors in determining the arrangement of pi-conjugated oligomers inside carbon nanotubes. AB - Density functional theory (DFT) calculations with dispersion corrections elucidated the key factors for determining the arrangement of pi-conjugated oligomers inside a carbon nanotube. The current study considered methyl terminated terfurans as guests inside a host tube; the results were compared with those obtained in previous studies for methyl-terminated terthiophenes inside a nanotube. DFT calculations found that the most important factor in determining the guest arrangement is the host-guest interactions arising from long-range CH pi and pi-pi interactions. In particular, the host-guest interactions play a crucial role in the arrangement of pi-conjugated oligomers inside a larger diameter tube: pi-conjugated oligomers sit near the inner tube wall to maximize attractive host-guest interactions. Within a smaller-diameter tube, host-guest interactions, as well as guest-guest (interchain) interactions, are responsible for the guest arrangement. Then, stronger host-guest (weaker guest-guest) interactions are a major (minor) factor. The stronger host-guest interactions are sufficient to deform the inner pi-conjugated oligomers. Due to the tube encapsulation, inner terfurans lose their planarity, leading to a weakening of the interchain interactions. In contrast, tube encapsulation induces terthiophenes to assume nearly planar structures, enhancing their interchain interactions. As a result, the magnitude of the interchain interactions is dependent on the type of inner oligomer. Reflecting the different interchain interactions, multimeric terfurans inside a nanotube exhibit molecular packings that are different from those of the corresponding terthiophenes. Considering the importance of the arrangement of inner pi-conjugated oligomers to their electronic properties, nanotube containers can thus tune the properties of inner oligomers. PMID- 26256515 TI - Balancing mitochondrial biogenesis and mitophagy to maintain energy metabolism homeostasis. PMID- 26256516 TI - Involvement of RARRES3 in the regulation of Wnt proteins acylation and signaling activities in human breast cancer cells. PMID- 26256517 TI - Induction of apoptosis by IFNgamma in human neuroblastoma cell lines through the CD95/CD95L autocrine circuit. PMID- 26256518 TI - Magnetic field assisted programming of particle shapes and patterns. AB - Anisotropic particles have generated an enormous amount of research interest due to their applications for drug delivery, electronic displays and as micromotors. However, up till now, there is no single protocol capable of generating particles of "patchy" composition with a variety of well-defined and predictable shapes. To address this, in this submission we dispersed magnetic nanoparticles (MNPs) in a non-magnetic fluid containing monomer and crosslinker. This solution was added to the surface of Teflon, which was submerged in the solvent 2,2,4-trimethylpentane. Under these conditions a round, stable droplet was formed on the Teflon. Upon exposure to a permanent magnet, the MNPs self-assembled into clusters with a variety shapes and sizes. The shape and size of the clusters depended on the magnetic field strength, which we controlled by systematically varying the distance between the magnet and the droplet. Interestingly, the shape of the liquid droplet was also influenced by the magnetic field. Upon polymerization, the MNP patterns and the droplet shape was preserved. We also show that very complex MNP patterns and particle shapes could be generated by controlling the distance between the drop and both a magnet above and below the droplet. In this case, the resulting patterns depended on whether the magnets were attracting or repelling each other, which was capable of changing the field lines that the MNPs align with. Overall, this approach is capable of generating particles with predictable MNP patterns and particle shapes without the use of any templates or complex synthetic steps. Furthermore, by using a sprayer (or similar approaches, e.g., ink jet printing) this technique can be easily scaled up to produce many complex anisotropic particles in a short amount of time. PMID- 26256519 TI - Acute withdrawal-related hypophagia elicited by amphetamine is attenuated by pretreatment with selective dopamine D1 or D2 receptor antagonists in rats. AB - After receiving 2.0mg/kg amphetamine, rats show two phases of reduced food intake, short-term hypophagia, during the first several hours after treatment, and longer-term hypophagia, approximately 19 to 26 h after treatment. The longer term hypophagia may be an indicator of an acute withdrawal. This study assessed whether D1 and D2 receptor activation were important early events in the elicitation of longer-term hypophagia. Throughout a series of five-day tests, rats could lever press for food pellets for one-hour periods beginning every 3h. On test day 1, rats were given a saline pretreatment, and 15 min later they were given a saline treatment. On test day 3, they were given a pretreatment of either saline or a selective dopamine receptor antagonist, and 15 min later they were given a treatment of either saline or amphetamine (2.0mg/kg). In Experiment 1, pretreatments included 3, 12, 31, and 50 MUg/kg of the selective D1 receptor antagonist SCH 23390. In Experiment 2, pretreatments included 25, 50, and 100 MUg/kg of the selective D2 receptor antagonist eticlopride. Distance moved was monitored for the first 6h following pretreatment-treatment combinations to obtain an indirect behavioral measure of receptor blockade (antagonist attenuation of amphetamine hyperactivity). Food intake at each meal opportunity was monitored throughout each five day test. Patterns of food intake following day 1 saline-saline and day 3 pretreatment-treatment were compared. The combination saline-amphetamine produced short-term and longer-term hypophagia. Combinations involving antagonist-saline did not produce longer-term changes in food intake. Pretreatment with 12 to 50 MUg/kg of SCH 23390 produced substantial blockade of amphetamine hyperactivity and prevented amphetamine-induced acute withdrawal-related longer-term hypophagia. Eticlopride produced a partial blockade of longer-term hypophagia. Both D1 and D2 receptor activation are required for full expression of longer-term hypophagia following amphetamine administration. PMID- 26256521 TI - Fine-tuning Risk Stratification for Non-Muscle-invasive Bladder Cancer. PMID- 26256520 TI - Poor quality of life, depressed mood, and memory impairment may be mediated by sleep disruption in patients with Addison's disease. AB - Standard replacement therapy for Addison's disease (AD) does not restore a normal circadian rhythm. In fact, hydrocortisone replacement in AD patients likely induces disrupted sleep. Given that healthy sleep plays an important role in improving quality of life, optimizing cognition, and ensuring affect regulation, the aim of this study was to investigate whether poor quality of life, mood alterations, and memory complaints reported by AD patients are associated with their disrupted sleep patterns. Sixty patients with AD and 60 matched healthy controls completed a battery of self-report questionnaires assessing perceived physical and mental health (Short-Form 36), mood (Beck Depression Inventory-II), sleep quality (Pittsburgh Sleep Quality Index), and cognition (Cognitive Failures Questionnaire). A latent variable model revealed that although AD had a significant direct effect on quality of life, the indirect effect of sleep was significantly greater. Furthermore, although AD had no direct effect on cognitive functioning, the indirect effect of sleep was significant. The overall model showed a good fit (comparative fit index = 0.91, root mean square of approximation = 0.09, and standardized root mean square residual = 0.05). Our findings suggest that disrupted sleep, and not the disease per se, may induce poor quality of life, memory impairment, and affect dysregulation in patients with AD. We think that improving sleep architecture may improve cognitive, affective, and physical functioning. PMID- 26256522 TI - Structural classification of metal complexes with three-coordinate centres. AB - Attempts to describe the geometry about three-coordinate silver(i) complexes have proven difficult because interatomic angles generally vary wildly and there is no adequate or readily available classification system found in the literature. A search of the Cambridge Structural Database shows that complexes formed between any metal centre and three non-metal donors (18 001 examples) usually adopt geometries that are quite different than ideal 'textbook' extremes of either trigonal planar (~4% with alpha = beta = gamma = 120 +/- 2 degrees ), T-shaped (~0.05% with alpha = 180 +/- 2 degrees , beta = gamma = 90 +/- 2 degrees ), or trigonal pyramidal (~0.3% with alpha = beta = gamma = 110 +/- 2 degrees ). Moreover, there are multiple variations of "Y-type" and "other" shapes that require elaboration. Thus, to assist in future structural descriptions, we developed a classification system that spans all known and yet-to-be-discovered three-coordinate geometries. A spreadsheet has also been constructed that utilizes the "shape-space" approach to extract the structural description from a user input of three angles about a tri-coordinate centre and the number of atoms in a plane. The structures of two silver(i) complexes of new N-donor ligands p NH2C6H4C6H4CH(pz = pyrazol-1-yl)2, L1, and 2-ferrocenyl-4,5-di(2 pyridyl)imidazole, L2, illustrate the utility of this classification system. PMID- 26256524 TI - Maternal immunization at the crossroads. PMID- 26256523 TI - Transcriptional changes induced by candidate malaria vaccines and correlation with protection against malaria in a human challenge model. AB - INTRODUCTION: The complexity of immunity to malaria is well known, and clear correlates of protection against malaria have not been established. A better understanding of immune markers induced by candidate malaria vaccines would greatly enhance vaccine development, immunogenicity monitoring and estimation of vaccine efficacy in the field. We have previously reported complete or partial efficacy against experimental sporozoite challenge by several vaccine regimens in healthy malaria-naive subjects in Oxford. These include a prime-boost regimen with RTS,S/AS02A and modified vaccinia virus Ankara (MVA) expressing the CSP antigen, and a DNA-prime, MVA-boost regimen expressing the ME TRAP antigens. Using samples from these trials we performed transcriptional profiling, allowing a global assessment of responses to vaccination. METHODS: We used Human RefSeq8 Bead Chips from Illumina to examine gene expression using PBMC (peripheral blood mononuclear cells) from 16 human volunteers. To focus on antigen-specific changes, comparisons were made between PBMC stimulated with CSP or TRAP peptide pools and unstimulated PBMC post vaccination. We then correlated gene expression with protection against malaria in a human Plasmodium falciparum malaria challenge model. RESULTS: Differentially expressed genes induced by both vaccine regimens were predominantly in the IFN-gamma pathway. Gene set enrichment analysis revealed antigen-specific effects on genes associated with IFN induction and proteasome modules after vaccination. Genes associated with IFN induction and antigen presentation modules were positively enriched in subjects with complete protection from malaria challenge, while genes associated with haemopoietic stem cells, regulatory monocytes and the myeloid lineage modules were negatively enriched in protected subjects. CONCLUSIONS: These results represent novel insights into the immune repertoires involved in malaria vaccination. PMID- 26256525 TI - How should influenza be treated? Focus on antivirals. PMID- 26256526 TI - Maternal antibodies and infant immune responses to vaccines. AB - Infants are born with immature immune systems, making it difficult for them to effectively respond to the infectious pathogens encountered shortly after birth. Maternal antibody is actively transported across the placenta and serves to provide protection to the newborn during the first weeks to months of life. However, maternal antibody has been shown repeatedly to inhibit the immune responses of young children to vaccines. The mechanisms for this inhibition are presented and the impact on ultimate immune responses is discussed. PMID- 26256527 TI - The US FDA pregnancy lactation and labeling rule - Implications for maternal immunization. AB - The FDA has responsibility for ensuring that prescription drug and biological products including vaccines are accompanied by labeling that summarizes scientific information concerning their safe and effective use. As part of a broader effort to improve the content and format of prescription drug labeling FDA published a final rule, the Content and Format of Labeling for Human Prescription Drug and Biological Products; Requirements for Pregnancy and Lactation Labeling, referred to as the "Pregnancy and Lactation Labeling Rule (PLLR)." The most significant change to be implemented by this Rule is the removal of the letter risk categories A, B, C, D and X from all labeling, replacing them with a narrative summary of the risks of using a drug or biological product including vaccines during pregnancy. The PLLR requires an evaluation of available information about a product's use in pregnancy and provides an opportunity to update labeling when new information about use of a vaccine in pregnancy becomes available. Implementation of the provisions articulated in the PLLR, as they apply to vaccine product labeling, will require close collaboration between FDA and the vaccine manufacturer for both currently licensed vaccines and those in development. PMID- 26256528 TI - Profiling the host response to malaria vaccination and malaria challenge. AB - A vaccine for malaria is urgently required. The RTS,S vaccine represents major progress, but is only partially effective. Development of the next generation of highly effective vaccines requires elucidation of the protective immune response. Immunity to malaria is known to be complex, and pattern-based approaches such as global gene expression profiling are ideal for understanding response to vaccination and protection against disease. The availability of experimental sporozoite challenge in humans to test candidate malaria vaccines offers a precious opportunity unavailable for other current targets of vaccine research such as HIV, tuberculosis and Ebola. However, a limited number of transcriptional profiling studies in the context of malaria vaccine research have been published to date. This review outlines the background, existing studies, limits and opportunities for gene expression studies to accelerate malaria vaccine research. PMID- 26256529 TI - An antenna model for the Purcell effect. AB - The Purcell effect is defined as a modification of the spontaneous emission rate of a quantum emitter at the presence of a resonant cavity. However, a change of the emission rate of an emitter caused by an environment has a classical counterpart. Any small antenna tuned to a resonance can be described as an oscillator with radiative losses, and the effect of the environment on its radiation can be modeled and measured in terms of the antenna radiation resistance, similar to a quantum emitter. We exploit this analogue behavior to develop a general approach for calculating the Purcell factors of different systems and various frequency ranges including both electric and magnetic Purcell factors. Our approach is illustrated by a general equivalent scheme, and it allows resenting the Purcell factor through the continuous radiation of a small antenna at the presence of an electromagnetic environment. PMID- 26256530 TI - Association between waist circumference and gray matter volume in 2344 individuals from two adult community-based samples. AB - We analyzed the putative association between abdominal obesity (measured in waist circumference) and gray matter volume (Study of Health in Pomerania: SHIP-2, N=758) adjusted for age and gender by applying volumetric analysis and voxel based morphometry (VBM) with VBM8 to brain magnetic resonance (MR) imaging. We sought replication in a second, independent population sample (SHIP-TREND, N=1586). In a combined analysis (SHIP-2 and SHIP-TREND) we investigated the impact of hypertension, type II diabetes and blood lipids on the association between waist circumference and gray matter. Volumetric analysis revealed a significant inverse association between waist circumference and gray matter volume. VBM in SHIP-2 indicated distinct inverse associations in the following structures for both hemispheres: frontal lobe, temporal lobes, pre- and postcentral gyrus, supplementary motor area, supramarginal gyrus, insula, cingulate gyrus, caudate nucleus, olfactory sulcus, para-/hippocampus, gyrus rectus, amygdala, globus pallidus, putamen, cerebellum, fusiform and lingual gyrus, (pre-) cuneus and thalamus. These areas were replicated in SHIP-TREND. More than 76% of the voxels with significant gray matter volume reduction in SHIP 2 were also distinct in TREND. These brain areas are involved in cognition, attention to interoceptive signals as satiety or reward and control food intake. Due to our cross-sectional design we cannot clarify the causal direction of the association. However, previous studies described an association between subjects with higher waist circumference and future cognitive decline suggesting a progressive brain alteration in obese subjects. Pathomechanisms may involve chronic inflammation, increased oxidative stress or cellular autophagy associated with obesity. PMID- 26256532 TI - CO2-selective PEO-PBT (PolyActiveTM)/graphene oxide composite membranes. AB - CO2-selective graphene oxide (GO) nano-composite membranes were prepared for the first time by embedding GO into a commercially available poly(ethylene oxide) poly(butylene terephthalate) (PEO-PBT) copolymer (PolyActiveTM). The as-prepared GO membrane shows high CO2 permeability (143 Barrer) and CO2/N2 selectivity (alpha = 73). PMID- 26256531 TI - Alpha-2 adrenergic agonists for the prevention of shivering following general anaesthesia. AB - BACKGROUND: Shivering after general anaesthesia is common. It is unpleasant but can also have adverse physiological effects. Alpha-2 (alpha-2) adrenergic agonist receptors, which can lead to reduced sympathetic activity and central regulation of vasoconstrictor tone, are a group of drugs that have been used to try to prevent postoperative shivering. OBJECTIVES: To assess the following: the effects of alpha-2 agonists on the prevention of shivering and subsequent complications after general anaesthesia in people undergoing surgery; the effects of alpha-2 agonists on the risk of inadvertent perioperative hypothermia; and whether any adverse effects are associated with these interventions. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE on 13 June 2014. Our search terms were relevant to the review question and limited to studies that assessed shivering or hypothermia. We also carried out searches of clinical trials registers, and forward and backward citation tracking. SELECTION CRITERIA: We considered all randomized controlled trials, quasi-randomized studies, and cluster-randomized studies with adult participants undergoing surgery with general anaesthesia in which an alpha-2 agonist was compared with another alpha-2 agonist or a placebo for the prevention of shivering. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data, consulting a third review author in the case of disagreements. We used standard Cochrane methodological procedures, including an assessment of risk of bias and use of GRADEpro software to interpret findings. MAIN RESULTS: We included 20 studies with 1401 surgical participants comparing an alpha-2 agonist against a control. Thirteen studies compared clonidine with a control, whilst seven compared dexmedetomidine with a control. The doses, methods, and time of administration varied between studies: three studies gave the drug orally or as an intravenous bolus preoperatively and nine intraoperatively; one study gave the drug as an infusion starting preoperatively and seven started at varying points from anaesthetic induction to the end of surgery. Whilst all the studies were described as randomized, many provided insufficient detail on methods used. We had anticipated that attempts would be made to reduce performance bias by blinding of personnel and participants, however this was detailed in only six of the papers. Similarly, in some studies detail was lacking on methods to reduce the risk of detection bias. We therefore downgraded the quality of evidence in our 'Summary of findings' table by one level for risk of bias using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach.All 20 included studies presented outcome data for postoperative shivering, and in meta-analysis alpha-2 agonists were shown to significantly reduce the risk of shivering (Mantel-Haenszel risk ratio 0.28, 95% confidence interval 0.18 to 0.43, P value < 0.0001). We found significant evidence of heterogeneity (I(2) = 80%) for this result that was not explained by sensitivity or subgroup analysis; we therefore downgraded the inconsistency of the evidence by one level. Although we did not feel that there were concerns with imprecision or indirectness of the data, we downgraded the quality of the evidence for the risk of publication bias following visual analysis of a funnel plot. Using GRADEpro, we rated the overall quality of the data for shivering as very low. Only one study reported the incidence of core hypothermia, whilst 12 studies measured core temperature. However, as the results for core temperature were reported in different styles, pooling the results was inappropriate. We found no studies with participant-reported outcomes such as experience of shivering or participant satisfaction. We found limited data for the outcomes of length of stay in the postanaesthetic care unit (three studies, 200 participants) and the following adverse effects: sedation (nine studies, 875 participants), bradycardia (eight studies, 716 participants), and hypotension (seven studies, 688 participants). Unpooled analysis suggested that sedation and bradycardia were significantly more common with dexmedetomidine than placebo, with all seven dexmedetomidine studies and none of the clonidine studies reporting statistically significantly higher levels of sedation as an adverse effect. AUTHORS' CONCLUSIONS: There is evidence that clonidine and dexmedetomidine can reduce postoperative shivering, but patients given dexmedetomidine may be more sedated. However, our assessment of the quality of this evidence is very low. PMID- 26256533 TI - Piezotronic Effect in Polarity-Controlled GaN Nanowires. AB - Using high-quality and polarity-controlled GaN nanowires (NWs), we studied the piezotronic effect in crystal orientation defined wurtzite structures. By applying a normal compressive force on c-plane GaN NWs with an atomic force microscopy tip, the Schottky barrier between the Pt tip and GaN can be effectively tuned by the piezotronic effect. In contrast, the normal compressive force cannot change the electron transport characteristics in m-plane GaN NWs whose piezoelectric polarization axis is turned in the transverse direction. This observation provided solid evidence for clarifying the difference between the piezotronic effect and the piezoresistive effect. We further demonstrated a high sensitivity of the m-plane GaN piezotronic transistor to collect the transverse force. The integration of c-plane GaN and m-plane GaN indicates an overall response to an external force in any direction. PMID- 26256534 TI - Effect of walking speed on gait sub phase durations. AB - Gait phase durations are important spatiotemporal parameters in different contexts such as discrimination between healthy and pathological gait and monitoring of treatment outcomes after interventions. Although gait phases strongly depend on walking speed, the influence of different speeds has rarely been investigated in literature. In this work, we examined the durations of the stance sub phases and the swing phase for 12 different walking speeds ranging from 0.6 to 1.7 m/s in 21 healthy subjects using infrared cinematography and an instrumented treadmill. We separated the stance phase into loading response, mid stance, terminal stance and pre-swing phase and we performed regression modeling of all phase durations with speed to determine general trends. With an increasing speed of 0.1m/s, stance duration decreased while swing duration increased by 0.3%. All distinct stance sub phases changed significantly with speed. These findings suggest the importance of including all distinct gait sub phases in spatiotemporal analyses, especially when different walking speeds are involved. PMID- 26256535 TI - The Structure of YnaI Implies Structural and Mechanistic Conservation in the MscS Family of Mechanosensitive Channels. AB - Mechanosensitive channels protect bacteria against lysis caused by a sudden drop in osmolarity in their surroundings. Besides the channel of large conductance (MscL) and small conductance (MscS), Escherichia coli has five additional paralogs of MscS that are functional and widespread in the bacterial kingdom. Here, we present the structure of YnaI by cryo-electron microscopy to a resolution of 13 A. While the cytosolic vestibule is structurally similar to that in MscS, additional density is seen in the transmembrane (TM) region consistent with the presence of two additional TM helices predicted for YnaI. The location of this density suggests that the extra TM helices are tilted, which could induce local membrane curvature extending the tension-sensing paddles seen in MscS. Off center lipid-accessible cavities are seen that resemble gaps between the sensor paddles in MscS. The conservation of the tapered shape and the cavities in YnaI suggest a mechanism similar to that of MscS. PMID- 26256536 TI - The Mechanism of ATP-Dependent Allosteric Protection of Akt Kinase Phosphorylation. AB - Kinases use ATP to phosphorylate substrates; recent findings underscore the additional regulatory roles of ATP. Here, we propose a mechanism for allosteric regulation of Akt1 kinase phosphorylation by ATP. Our 4.7-MUs molecular dynamics simulations of Akt1 and its mutants in the ATP/ADP bound/unbound states revealed that ATP occupancy of the ATP-binding site stabilizes the closed conformation, allosterically protecting pT308 by restraining phosphatase access and key interconnected residues on the ATP->pT308 allosteric pathway. Following ATP->ADP hydrolysis, pT308 is exposed and readily dephosphorylated. Site-directed mutagenesis validated these predictions and indicated that the mutations do not impair PDK1 and PP2A phosphatase recruitment. We further probed the function of residues around pT308 at the atomic level, and predicted and experimentally confirmed that Akt1(H194R/R273H) double mutant rescues pathology-related Akt1(R273H). Analysis of classical Akt homologs suggests that this mechanism can provide a general model of allosteric kinase regulation by ATP; as such, it offers a potential avenue for allosteric drug discovery. PMID- 26256537 TI - Advances in Single-Particle Electron Cryomicroscopy Structure Determination applied to Sub-tomogram Averaging. AB - Recent innovations in specimen preparation, data collection, and image processing have led to improved structure determination using single-particle electron cryomicroscopy (cryo-EM). Here we explore some of these advances to improve structures determined using electron cryotomography (cryo-ET) and sub-tomogram averaging. We implement a new three-dimensional model for the contrast transfer function, and use this in a regularized likelihood optimization algorithm as implemented in the RELION program. Using direct electron detector data, we apply both single-particle analysis and sub-tomogram averaging to analyze radiation induced movements of the specimen. As in single-particle cryo-EM, we find that significant sample movements occur during tomographic data acquisition, and that these movements are substantially reduced through the use of ultrastable gold substrates. We obtain a sub-nanometer resolution structure of the hepatitis B capsid, and show that reducing radiation-induced specimen movement may be central to attempts at further improving tomogram quality and resolution. PMID- 26256538 TI - Cooperative Dynamics of Intact AMPA and NMDA Glutamate Receptors: Similarities and Subfamily-Specific Differences. AB - Ionotropic glutamate receptors (iGluRs) are tetrameric ion channels that mediate excitatory neurotransmission. Recent structures of alpha-amino-3-hydroxy-5-methyl 4-isoxazole propionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors permit a comparative analysis of whole-receptor dynamics for the first time. Despite substantial differences in the packing of their two-domain extracellular region, the two iGluRs share similar dynamics, elucidated by elastic network models. Motions accessible to either structure enable conformational interconversion, such as compression of the AMPA receptor toward the more tightly packed NMDA receptor conformation, which has been linked to allosteric regulation. Pivoting motions coupled to concerted rotations of the transmembrane ion channel are prominent between dimers of distal N-terminal domains in the loosely packed AMPA receptor. The occurrence and functional relevance of these motions is verified by cross-linking experiments designed to probe the computationally predicted distance changes. Together with the identification of hotspot residues acting as mediators of allosteric communication, our data provide a glimpse into the dynamic spectrum of iGluRs. PMID- 26256540 TI - A Native-like Intermediate Serves as a Branching Point between the Folding and Aggregation Pathways of the Mouse Prion Protein. AB - Transient folding intermediates and/or partially unfolded equilibrium states are thought to play a key role in the formation of protein aggregates. However, there is only indirect evidence linking accumulation of folding intermediates to aggregation, and the underlying mechanism remains to be elucidated. Here, we show that a partially unfolded state of the prion protein accumulates both as a stable equilibrium state at acidic pH (A-state) and as a late folding intermediate. With a time resolution of approximately 60 MUs, we systematically studied the kinetics of folding and unfolding, starting from various initial conditions including the U-, N-, and A-states. Quantitative modeling showed that the observed kinetic data are completely consistent with a sequential four-state mechanism where the A state is a late folding intermediate. Combined with previous evidence linking A state accumulation to aggregation, the results indicate that this native-like state serves as a branching point between the folding and aggregation pathways. PMID- 26256539 TI - A YidC-like Protein in the Archaeal Plasma Membrane. AB - Cells possess specialized machinery to direct the insertion of membrane proteins into the lipid bilayer. In bacteria, the essential protein YidC inserts certain proteins into the plasma membrane, and eukaryotic orthologs are present in the mitochondrial inner membrane and the chloroplast thylakoid membrane. The existence of homologous insertases in archaea has been proposed based on phylogenetic analysis. However, limited sequence identity, distinct architecture, and the absence of experimental data have made this assignment ambiguous. Here we describe the 3.5-A crystal structure of an archaeal DUF106 protein from Methanocaldococcus jannaschii (Mj0480), revealing a lipid-exposed hydrophilic surface presented by a conserved YidC-like fold. Functional analysis reveals selective binding of Mj0480 to ribosomes displaying a stalled YidC substrate, and a direct interaction between the buried hydrophilic surface of Mj0480 and the nascent chain. These data provide direct experimental evidence that the archaeal DUF106 proteins are YidC/Oxa1/Alb3-like insertases of the archaeal plasma membrane. PMID- 26256541 TI - Evaluation of the relationship between education and sustainability in peasant movements: The experience of the National Education Program in Agrarian Reform. AB - Brazil is one of the largest agricultural producers in the world. However, its agrarian composition is based on two markedly different production models, particularly in relation to sustainability: a peasant family agriculture, which plays an important role in food production for domestic consumption and advocates agro-ecological practises; and agribusiness, the politically and economically hegemonic model that produces commodities for export based on monoculture and intensive use of pesticides. Therefore, in order to create the means to develop peasant lands, social movements and peasants have engaged themselves politically and defended an education model grounded in sustainable practises of production and social organisation. Taking this into account, the main purpose of this paper is to analyse and assess the Brazilian experience of integration between education and sustainability, in the National Education Program in Agrarian Reform (PRONERA). To accomplish this aim, a survey with a semi-structured questionnaire was carried out among teachers, students, monitors, and coordinators of the course offered by PRONERA. The surveys showed that the courses are promoting the concepts of sustainability among peasants. However, many adjustments need to be taken into consideration during the planning process for the next courses offered by PRONERA. PMID- 26256543 TI - Advances in capillary electrophoresis for miniaturizing assays on kinase enzymes for drug discovery. AB - CE has become a frequently used tool for miniaturizing enzyme assays due particularly to its well-recognized low sample consumption. CE-based enzyme assays cover all aspects of kinetic analysis including the evaluation of enzyme activity, substrate and modulator characterization, and identification. These assays are performed to conduct high-quality primary (hit finding) and secondary (confirmation by determining the half maximal inhibitory concentration, IC50 ) screening. Nowadays, the kinase family is among the most actively studied pharmaceutical targets in oncology, and in neurodegenerative and inflammation diseases. In this article, we review the fundamentals of the different approaches that may be employed for assaying kinase kinetics. Their advantages and limitations will also be discussed by covering the literature of CE-based assays for purified kinases as well as for kinases in living cells. The last section will be devoted to perspectives by showing some applications of multiplexed and of microchip devices for high-throughput screening kinase assays. PMID- 26256542 TI - Development of an immunochromatographic lateral flow device for rapid detection of Helicobacter pylori stool antigen. AB - OBJECTIVE: Helicobacter pylori stool antigen (HpSA) test is a convenient and reliable non-invasive diagnosis for H. pylori infection. The aim of this study is to develop an immunochromatographic testing device for rapid detection of HpSA among Chinese patients. DESIGN AND METHODS: Monoclonal antibodies (McAb) targeting H. pylori were developed by conventional methods and paired by sandwich ELISA. The lateral flow device (LFD) was prepared using the selected McAb pair. A total of 867 clinically separated bacterial strains, including 56H. pylori strains, were employed to test the sensitivity and specificity. Subsequently, the LFD was used to test 1200 human fecal samples, with a commercial HpSA testing device as comparison. RESULTS: Two McAb pairs targeting H. pylori, DF2a/EE10b and IH10b/EE10b, were developed and proven to be of high specificity and sensitivity. After testing the cultures of 56 clinically separated H. pylori strains, the final LFD product was prepared using the mixture of DF2a and IH10b as capture antibodies and EE10b as the detection antibody. The testing threshold for H. pylori culture was 1.0 * 10(4)cfu/mL. The sensitivity and specificity were both 100% for the 867 tested bacterial cultures. The testing results of 1200 fecal samples showed that the positive and negative agreement rates between the homemade LFD and the commercial testing device were 99.75% and 99.87%, respectively. CONCLUSION: Our homemade HpSA LFD can be a very promising testing device for rapid diagnosis and epidemic screening of H. pylori infection among Chinese patients. PMID- 26256544 TI - Role of adrenal vein sampling in primary aldosteronism: the Monash Health experience. AB - BACKGROUND: Adrenal vein sampling (AVS) is useful for distinguishing unilateral versus bilateral hypersecretion in primary aldosteronism (PA), but is technically challenging. Furthermore, the use of adrenocorticotropic hormone (ACTH) stimulation in AVS is controversial. We implemented a Monash Health-specific AVS protocol in 2010. AIM: The audit aimed to: (i) examine the impact of a dedicated protocol on success rates of AVS at a tertiary referral centre; (ii) evaluate the impact of AVS on sub-typing of PA; and (iii) assess the utility of ACTH stimulation in AVS. METHODS: AVS was performed on patients with PA confirmed by positive saline suppression testing (aldosterone level >140 pmol/L post-saline infusion), with sequential sampling of adrenal and peripheral veins, pre- and post-ACTH infusion. Patients with unilateral aldosterone-producing adenoma diagnosed on successful AVS were referred for adrenalectomy. RESULTS: Between 2010 and 2014 inclusive, a total of 28 AVS procedures was performed, with complete pre- and post-ACTH data for 19 procedures. Bilateral successful cannulation rates improved post-implementation of our protocol (61% vs 41%). Of the patients, 32% had discordant imaging and AVS results: four patients with unilateral adenomas did not lateralise on AVS and were managed medically; four patients with bilateral or no adenomas on imaging, lateralised on AVS and had surgery. Overall, use of ACTH did not increase successful cannulation and tended to mask lateralisation. CONCLUSION: AVS is crucial in subtype classification of PA and should be performed by a dedicated radiologist with a standardised protocol. AVS outcomes were not improved with the use of ACTH stimulation. PMID- 26256545 TI - Functions of synapsins in corticothalamic facilitation: important roles of synapsin I. AB - KEY POINTS: The synaptic vesicle associated proteins synapsin I and synapsin II have important functions in synaptic short-term plasticity. We investigated their functions in cortical facilitatory feedback to neurons in dorsal lateral geniculate nucleus (dLGN), feedback that has important functions in state dependent regulation of thalamic transmission of visual input to cortex. We compared results from normal wild-type (WT) mice and synapsin knockout (KO) mice in several types of synaptic plasticity, and found clear differences between the responses of neurons in the synapsin I KO and the WT, but no significant differences between the synapsin II KO and the WT. These results are in contrast to the important role of synapsin II previously demonstrated in similar types of synaptic plasticity in other brain regions, indicating that the synapsins can have different roles in similar types of STP in different parts of the brain. ABSTRACT: The synaptic vesicle associated proteins synapsin I (SynI) and synapsin II (SynII) have important functions in several types of synaptic short-term plasticity in the brain, but their separate functions in different types of synapses are not well known. We investigated possible distinct functions of the two synapsins in synaptic short-term plasticity at corticothalamic synapses on relay neurons in the dorsal lateral geniculate nucleus. These synapses provide excitatory feedback from visual cortex to the relay cells, feedback that can facilitate transmission of signals from retina to cortex. We compared results from normal wild-type (WT), SynI knockout (KO) and SynII KO mice, in three types of synaptic plasticity mainly linked to presynaptic mechanism. In SynI KO mice, paired-pulse stimulation elicited increased facilitation at short interpulse intervals compared to the WT. Pulse-train stimulation elicited weaker facilitation than in the WT, and also post-tetanic potentiation was weaker in SynI KO than in the WT. Between SynII KO and the WT we found no significant differences. Thus, SynI has important functions in these types of synaptic plasticity at corticothalamic synapses. Interestingly, our data are in contrast to the important role of SynII previously shown for sustained synaptic transmission during intense stimulation in excitatory synapses in other parts of the brain, and our results suggest that SynI and SynII may have different roles in similar types of STP in different parts of the brain. PMID- 26256546 TI - A detailed protocol for a rapid analysis of testicular cell populations using flow cytometry. AB - Accurate analysis and quantification of different testicular cell populations are of central importance in studies of male reproductive biology. The traditional histomorphometric and immunohistochemical methods remain the gold standard in studying the complex dynamics of the testicular tissue. Through past years advances have been made in the application of flow cytometry for the rapid analysis of testicular cell populations. Detection of DNA content and of surface antigens and fluorescent reporters have been widely used to analyze and sort cells. Detection of intracellular antigens can broaden the possibilities of applying flow cytometry in studies of male reproduction. Here, we report a detailed protocol for the preparation of rat testicular tissue for detection of intracellular antigens by flow cytometry, and a pipeline for subsequent data analysis and troubleshooting. Rat testicular ontogenesis was chosen as the experimental model to validate the performance of the assay using vimentin and gammaH2AX as intracellular markers for the somatic and spermatogenic cells, respectively. The results show that the assay is reproducible and recapitulates the rat testis ontogenesis. PMID- 26256547 TI - Management of hearing loss and the normal ear in cases of unilateral Microtia with aural atresia. AB - OBJECTIVES/HYPOTHESIS: To identify the rate of hearing loss related to middle ear disease and the frequency of tympanostomy tube (TT) insertion in the contralateral ear of patients with unilateral microtia/aural atresia. STUDY DESIGN: Retrospective case series of patients less than 3 years of age with unilateral microtia/aural atresia treated at an urban, tertiary care children's hospital from 2008 to 2013. METHODS: Clinical and audiologic data were reviewed. Statistical analysis was performed to determine the relative risk of TT insertion in the normal ear. RESULTS: A total of 72 patients were included for analysis. The average age of patients at their initial otolaryngology visit was 3.3 months (range 0.08-1.67 years); 38 (52.8%) patients were males. Aural atresia involved the right ear in 43 (59.7%) cases. Five (6.9%) patients were syndromic. Abnormal audiometric testing of the normal ear was noted in 12 (16.7%), and 14 (19.4%) underwent TT during the first 3 years of life. Twelve children (85.7%) who had a TT placed were nonsyndromic. When compared to published norms for TT placement in the general population (6.8% of children < 3 year of age), a greater proportion of children with unilateral microtia/aural atresia had TT placement in the normal ear (z = 4.26, P < 0.0001). CONCLUSION: Patients with unilateral microtia/aural atresia have increased rates of hearing loss and middle ear effusion leading to TT in their normal ear at a higher rate versus the general population. This information can help guide more vigilant care and audiologic follow-up in affected children. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1470-1474, 2016. PMID- 26256548 TI - Prevalence of beta-Lactamase Producing Escherichia coli from Retail Meat in Turkey. AB - Extended spectrum beta-lactamase (ESBL) and plasmid-mediated AmpC beta-lactamase (pAmpC) producing Escherichia coli have been shown to be present in humans and animals representing a significant problem worldwide. This study aimed to search the presence of ESBL and/or AmpC-producing E. coli in retail meats (chicken and beef) in Turkey. A total of 88 beta-lactamase-producing E. coli were isolated from chicken (n = 81/100) and beef meat (n = 7/100) samples and their susceptibility to several antimicrobials were tested using disc diffusion method. E. coli isolates were further characterized for their phylogenetic groups. beta Lactamase encoding (blaTEM , blaSHV , blaOXA , blaCTX-M , and blaAmpC ) and quinolone resistance genes (qnrA, qnrB, qnrS, qepA, and acc(6')-Ib-cr) were also secreened by polymerase chain reaction (PCR). However, in regard to beta lactamase genes, 84 of 88 isolates were positive for blaCTX-M-1 (n = 39), blaCTX M-3 (n = 5), blaCTX-M-15 (n = 4), blaTEM-1b (n = 2), blaSHV-12 (n = 1), blaCTX-M 1 /blaTEM-1b (n = 10), blaCTX-M-1 /blaTEM-1b /blaSHV-5 (n = 1), blaCTX-M-1 /blaCMY-2 (n = 1) and blaTEM-1b /blaCMY-2 (n = 6), blaCTX-M-15 /blaSHV-12 (n = 1), blaCTX-M-15 /blaTEM-1b (n = 1), blaTEM-1b /blaSHV-12 (n = 1), and blaCMY-2 (n = 12) genes. Resistance to cefuroxime (75.6% and 85.7%), nalidixic acid (89% and 85.7%), tetracycline (91.4% and 100%), streptomycin (40.2% and 100%), and trimethoprim-sulfamethoxazole (36.6% and 85.7%) was observed among strains isolated from chicken and beef, respectively. However, all isolates were found to be susceptible to amikacin, imipenem, and cefepime. Resistance to ampicillin and cefoxitin was significantly linked to blaCMY-2 gene, while there was a significant correlation between CTX-M type ESBL and antimicrobial resistance to cefuroxime and streptomycin (P < 0.05). The results of this study suggest that raw chicken retail meats are highly contaminated with ESBL-producing E. coli implementing a great risk to human health in Turkey. PMID- 26256549 TI - Population Landscape of Familial Cancer. AB - Public perception and anxiety of familial cancer have increased demands for clinical counseling, which may be well equipped for gene testing but less prepared for counseling of the large domain of familial cancer with unknown genetic background. The aim of the present study was to highlight the full scope of familial cancer and the variable levels of risk that need to be considered. Data on the 25 most common cancers were obtained from the Swedish Family Cancer Database and a Poisson regression model was applied to estimate relative risks (RR) distinguishing between family histories of single or multiple affected first degree relatives and their diagnostic ages. For all cancers, individual risks were significantly increased if a parent or a sibling had a concordant cancer. While the RRs were around 2.00 for most cancers, risks were up to 10-fold increased for some cancers. Familial risks were even higher when multiple relatives were affected. Although familial risks were highest at ages below 60 years, most familial cases were diagnosed at older ages. The results emphasized the value of a detailed family history as a readily available tool for individualized counseling and its preventive potential for a large domain of non syndromatic familial cancers. PMID- 26256550 TI - Utility-based optimization of phase II/III programs. AB - Phase II and phase III trials play a crucial role in drug development programs. They are costly and time consuming and, because of high failure rates in late development stages, at the same time risky investments. Commonly, sample size calculation of phase III is based on the treatment effect observed in phase II. Therefore, planning of phases II and III can be linked. The performance of the phase II/III program crucially depends on the allocation of the resources to phases II and III by appropriate choice of the sample size and the rule applied to decide whether to stop the program after phase II or to proceed. We present methods for a program-wise phase II/III planning that aim at determining optimal phase II sample sizes and go/no-go decisions in a time-to-event setting. Optimization is based on a utility function that takes into account (fixed and variable) costs of the drug development program and potential gains after successful launch. The proposed methods are illustrated by application to a variety of scenarios typically met in oncology drug development. PMID- 26256551 TI - Intermittent versus Persistent Wolff-Parkinson-White Syndrome in Children: Electrophysiologic Properties and Clinical Outcomes. AB - BACKGROUND: Intermittent Wolff-Parkinson-White (WPW) syndrome is considered to have a lower risk of sudden death. Fewer data exist regarding electrophysiologic (EP) characteristics and the natural history of intermittent WPW in children. METHODS: All patients with WPW age 1-18 years at a single institution (1996-2013) were reviewed. Patients with intermittent preexcitation were compared to those with loss of preexcitation on Holter/exercise testing and those with persistent preexcitation. High-risk accessory pathway (AP) was defined as AP effective refractory period (APERP), block cycle length, or shortest preexcited RR interval during atrial fibrillation <=250 ms. RESULTS: A total of 295 patients were included: 226 (76.6%) persistent, 39 (13.2%) intermittent, and 30 (10.2%) loss of preexcitation Holter/exercise. There were no differences in symptoms between groups. Median interquartile range APERP was significantly longer in intermittent WPW (380 [320, 488] ms vs 320 [300, 350] ms persistent, 310 [290, 330] ms loss of preexcitation Holter/exercise; P = 0.0008). At baseline, there was no difference between groups in frequency of high-risk pathways. However, when isoproterenol values were included, high-risk pathways were more frequent among patients with loss of preexcitation on Holter/exercise (54% vs 16% persistent, 11% intermittent; P = 0.005). There was one death in a patient with loss of preexcitation on exercise testing, no EP study, and prior drug use. A second patient with persistent WPW and APERP 270 ms required resuscitation following a methadone overdose. CONCLUSION: Intermittent preexcitation in children does not connote a lower risk AP by EP criteria or reduced symptoms. The low number of pediatric WPW patients who develop preexcited atrial fibrillation or sudden death warrants larger studies to investigate these outcomes. PMID- 26256552 TI - Assessment of optic nerve development using post-mortem Magnetic Resonance Imaging (MRI) in fetuses and newborns. PMID- 26256554 TI - SirX: a selective inversion recovery experiment on X-nuclei for the determination of the exchange rate of slow chemical exchanges between two sites. AB - Nuclear magnetic resonance spectroscopy has proven to be powerful for the study of dynamic processes. A new pulse sequence, SirX, is designed to provide boundary conditions that simplify the McConnell equations. Both an initial rate approximation and a whole curve fitting to the time course of magnetization can be used to calculate the exchange rate. These methods were used to study the exchange kinetics of N,N-dimethylacetamide. As compared with the well-established exchange spectroscopy suitable to studies of slow exchange, SirX has the advantage of being less time consuming and capable of providing more reliable kinetic data. Furthermore, by setting the observation on X-nuclei with larger chemical shift dispersion as compared with an observation on (1)H resonance, SirX extends the upper limit of a reliable determination of exchange rates. PMID- 26256553 TI - CT-based analysis of pericoronary adipose tissue density: Relation to cardiovascular risk factors and epicardial adipose tissue volume. AB - BACKGROUND: Pericoronary adipose tissue (PCAT) can promote atherosclerosis. Metabolically active and inactive PCAT may display different CT densities. However, CT density could be influenced by partial volume effects and image interpolation. OBJECTIVE: To investigate whether PCAT density values in CT displays differences that are larger than those attributable to interpolation and partial volume effects, which would manifest themselves through the relationship between PCAT density and distance from the contrast-enhanced coronary lumen. METHODS: PCAT density analysis was performed (417 non-atherosclerotic segments, 63 patients) using dual-source CT with a threshold-based measurement method. Changes in PCAT density values depending on distance from the contrast-enhanced coronary lumen and the influence of cardiovascular risk profile were analyzed. RESULTS: Mean PCAT density was -78.1 +/- 5.6 HU. PCAT density decreased from proximal to distal segments in the LAD (-78.0 +/- 7.3 vs. -82.4 +/- 7.7 HU; p < 0.001). PCAT density was higher close to the lumen compared to more peripheral locations (-76.0 +/- 6.7 vs. -78.5 +/- 5.4 HU; p < 0.001). Decreasing PCAT density was significantly associated with higher epicardial adipose tissue (EAT) volume and body mass index. There was a trend of lower PCAT values with a family history of coronary artery disease. CONCLUSION: CT-measured attenuation of PCAT is influenced by EAT volume and body mass index. A decrease of PCAT attenuation with increasing distance from the vessel and from proximal to distal segments may suggest variations in CT density of PCAT due to partial volume effects and image interpolation rather than solely due to differences in tissue composition or metabolic activity. PMID- 26256555 TI - Effects of high-sugar and high-fiber meals on physical activity behaviors in Latino and African American adolescents. AB - OBJECTIVE: This crossover experimental study examined the acute effects of high sugar/low-fiber (HSLF) vs. low-sugar/high-fiber (LSHF) meals on sedentary behavior (SB) and light-plus activity (L+) in minority adolescents with overweight and obesity. METHODS: 87 Latino and African American adolescents (mean age = 16.3 +/- 1.2 years, mean BMI z-score = 2.02 +/- 0.52, 56.8% Latino, 51.1% male) underwent two experimental meal conditions during which they consumed HSLF or LSHF meals. Physical activity and SB were measured using accelerometers, and blood glucose and insulin were collected every 30 minutes over 5 hours. Mixed models were used to examine the temporal trends of SB and L+, whether the temporal trends of SB and L+ differed by meal condition, and the influence of blood glucose and insulin on the activity behaviors. RESULTS: SB and L+ fluctuated over time during the HSLF condition but were stable during the LSHF condition. SB and L+ were influenced by the blood glucose response to the HSLF meals. Insulin did not influence SB or L+ in either meal condition. CONCLUSIONS: Sugar and fiber content of meals can have differing acute impacts on activity behaviors in minority adolescents with overweight and obesity, possibly due to differing metabolic responses. PMID- 26256556 TI - What would Treg-cell biology look like when viewed from a rationalized perspective? AB - The argument that Treg cells play a role in determining the Self (S)-Nonself (NS) discrimination (i.e. tolerance) is challenged based on two theoretical constructs, the two stage-two signal model for the S-NS discrimination and the Tritope model of TCR function. The conclusions are then tested by reinterpreting a published probing set of data purporting to show that Treg cells regulate tolerance. It is concluded that the major role of suppression is to operate as a feedback mechanism modulating the magnitude of the effector response; it is not a determinant of the S-NS discrimination (i.e. tolerance). PMID- 26256557 TI - What is healthy food? Objective nutrient profile scores and subjective lay evaluations in comparison. AB - To date, it is unclear how consumers evaluate the healthiness of individual foods and meals and how consumers' perceptions are related to expert opinions. This knowledge is essential for efficient communication of nutrition information with the goal of promoting healthy eating. This study used the fake food buffet method to investigate health perceptions of selected meals and of 54 individual foods and beverages. Lay consumers' subjective healthiness evaluations of meals and foods were compared to objective nutrient profile scores, which were previously shown to correlate highly with expert opinions. The results show that nutrition profile scores and lay evaluations were highly correlated, which indicates that lay people used similar criteria as experts to evaluate the healthiness of foods. However, lay consumers tended to neglect the amount of saturated fat, protein and sodium for their judgments. Also, it was found that while lay consumers were quite able to evaluate single food products, they had difficulties in evaluating entire meals. Future interventions should focus particularly on educating the consumer about the negative effects of diets high in salt and saturated fat and they should improve the consumer's abilities to evaluate entire meals. PMID- 26256558 TI - Simulation of changes in diffusion related to different pathologies at cellular level after traumatic brain injury. AB - PURPOSE: The goal of the current study was to investigate tissue pathology at the cellular level in traumatic brain injury (TBI) as revealed by Monte Carlo simulation of diffusion tensor imaging (DTI)-derived parameters and elucidate the possible sources of conflicting findings of DTI abnormalities as reported in the TBI literature. METHODS: A model with three compartments separated by permeable membranes was employed to represent the diffusion environment of water molecules in brain white matter. The dynamic diffusion process was simulated with a Monte Carlo method using adjustable parameters of intra-axonal diffusivity, axon separation, glial cell volume fraction, and myelin sheath permeability. The effects of tissue pathology on DTI parameters were investigated by adjusting the parameters of the model corresponding to different stages of brain injury. RESULTS: The results suggest that the model is appropriate and the DTI-derived parameters simulate the predominant cellular pathology after TBI. Our results further indicate that when edema is not prevalent, axial and radial diffusivity have better sensitivity to axonal injury and demyelination than other DTI parameters. CONCLUSION: DTI is a promising biomarker to detect and stage tissue injury after TBI. The observed inconsistencies among previous studies are likely due to scanning at different stages of tissue injury after TBI. Magn Reson Med 76:290-300, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26256559 TI - A new adverse drug reaction--Schamberg's disease caused by amlodipine administration--a case report. PMID- 26256560 TI - Collagen duplicate genes of bone and cartilage participate during regeneration of zebrafish fin skeleton. AB - The zebrafish fin is widely used as a model for skeleton regeneration. For years, the nature of the fin skeleton has been controversial as its extracellular matrix shows hybrid characteristics of both bone and cartilage. The presence of co orthologs genes also increases the complexity of these tissues. In this article, we have identified and described the expression of fibrillar collagens in zebrafish fin skeleton. We found that genes coding for types I, II, V, XI and XXVII collagens are duplicated, showing in several cases, different expression domains. We also identified specific genomic features, such as the presence of type XXIV collagen and the absence of type III collagen in the zebrafish genome. Our study showed that actinotrichia-forming cells and osteoblasts synthesize a wide variety of these fibrillar collagens during fin regeneration. An intertrichial domain expressing most of the collagens was located in the transition between the mesenchyme condensations of actinotrichia and lepidotrichia and may determine an important niche associated with fin skeleton morphogenesis. We also confirmed the hybrid nature of the fin exoskeleton and provided a complete description of those fibrillar collagens expressed during the formation of the fin skeleton. PMID- 26256561 TI - The satisfaction of families in the care of their loved ones in CCUs in Lebanon. AB - BACKGROUND: The needs of family members vary among cultures and hospitals. Often, these needs remain unmet increasing their stress and anxiety and decreasing their satisfaction with care, which may negatively impact the quality of patient care. AIMS: To assess the satisfaction of families with the care of their loved ones in critical care units (CCUs) in a large university medical centre in Lebanon and to assess the predictors of satisfaction. METHODS: A cross-sectional descriptive design was conducted using the Critical Care Family Satisfaction Survey (CCFSS). The participants were 123 adult relatives or significant others of patients cared for in both adult and paediatric intensive care units for at least 3 days. RESULTS: The CCFSS showed acceptable internal reliability and construct validity in a Lebanese population. In general, families were satisfied with the care their loved ones received in the CCUs, and the least satisfaction was in the area of 'comfort' and the highest was in 'assurance'. Younger family members with more education were less satisfied with care and Christian families expressed less satisfaction with informational needs compared with Muslim families. Families of children in the paediatric CCU expressed least satisfaction with care. Gender, residency, relationship to patient, unit, prior experience in a CCU and diagnosis had no effect on satisfaction scores. CONCLUSIONS: Assessment of family satisfaction in different cultures is important as each culture has specific needs that are essential to decipher. IMPLICATIONS FOR PRACTICE: Patient satisfaction leads to improved quality of care; thus, it behoves nurses to meet the needs of families from different cultures to help them cope and increase their satisfaction, which leads to improve patient outcomes. PMID- 26256562 TI - 2015 ACC/HRS/SCAI Left Atrial Appendage Occlusion Device Societal Overview: A professional societal overview from the American College of Cardiology, Heart Rhythm Society, and Society for Cardiovascular Angiography and Interventions. PMID- 26256563 TI - Synthetic histone code. AB - Chromatin is the universal template of genetic information in all eukaryotic cells. This complex of DNA and histone proteins not only packages and organizes genomes but also regulates gene expression. A multitude of posttranslational histone modifications and their combinations are thought to constitute a code for directing distinct structural and functional states of chromatin. Methods of protein chemistry, including protein semisynthesis, amber suppression technology, and cysteine bioconjugation, have enabled the generation of so-called designer chromatin containing histones in defined and homogeneous modification states. Several of these approaches have matured from proof-of-concept studies into efficient tools and technologies for studying the biochemistry of chromatin regulation and for interrogating the histone code. We summarize pioneering experiments and recent developments in this exciting field of chemical biology. PMID- 26256564 TI - Magnetoencephalography in the study of children with autism spectrum disorder. AB - Magnetoencephalography (MEG) is a non-invasive neuroimaging technique that provides a measure of cortical neural activity on a millisecond timescale with high spatial resolution. MEG has been clinically applied to various neurological diseases, including epilepsy and cognitive dysfunction. In the past decade, MEG has also emerged as an important investigatory tool in neurodevelopmental studies. It is therefore an opportune time to review how MEG is able to contribute to the study of atypical brain development. We limit this review to autism spectrum disorder (ASD). The relevant published work for children was accessed using PubMed on 5 January 2015. Case reports, case series, and papers on epilepsy were excluded. Owing to their accurate separation of brain activity in the right and left hemispheres and the higher accuracy of source localization, MEG studies have added new information related to auditory-evoked brain responses to findings from previous electroencephalography studies of children with ASD. In addition, evidence of atypical brain connectivity in children with ASD has accumulated over the past decade. MEG is well suited for the study of neural activity with high time resolution even in young children. Although further studies are still necessary, the detailed findings provided by neuroimaging methods may aid clinical diagnosis and even contribute to the refinement of diagnostic categories for neurodevelopmental disorders in the future. PMID- 26256565 TI - Teenage cardiac arrest following abuse of synthetic cannabis. AB - INTRODUCTION: The cardiac effects of many illegal substances (cocaine, methadone) have previously been well described [1,2]. However the association between synthetic cannabis and cardiac arrest is less well documented. Here we describe an out-of-hospital cardiac arrest in a previously healthy 16-year-old female associated with the use of inhaled synthetic cannabis. METHODS: An electronic systematic search of online databases PubMed and Embase was performed using keywords, "synthetic cannabis death" and "cardiac arrest". RESULTS: In this case study a previously healthy 16-year-old had a cardiac arrest after synthetic cannabis use. Despite extensive investigations no other cause for her arrest was found. To the best of our knowledge there has been one previous case report of cardiac arrest following synthetic cannabis use in a 56-year-old man [3]. CONCLUSIONS: This case report augments the relationship between synthetic cannabis and cardiac arrest in the medical community. More awareness surrounding the risk of synthetic cannabinoids is warranted. PMID- 26256566 TI - County Health Rankings and the Cult of the Imperfect. PMID- 26256567 TI - Fresh frozen plasma transfusion fails to influence the hemostatic balance in critically ill patients with a coagulopathy: reply. PMID- 26256568 TI - The pattern of lip cancer occurrence over the 1990-2011 period in public hospitals in Madrid, Spain. AB - BACKGROUND: Some regions of Spain along with Canada and Australia have the highest rates of lip cancer in the world. The objective of this study was to examine the trends in the pattern of occurrence of lip cancer in Madrid, Spain. METHODS: Data were extracted from the Central Tumour Registry of Madrid, between 1990 and 2011. Variables examined were age, sex, topographic and morphological location and tumour histology. Two consecutive periods, 1990-2001 and 2002-2011, were studied by descriptive and analytical methods, and the data from the two periods were statistically compared. RESULTS: A total of 881 cases were registered during the period 1990-2011. Comparing data between the two periods (1990-2001 and 2002-2011), subtle variations in age, histology and location were noted. Gender ratios remained constant. The mean age increased from 66.3 to 69.7 years (P < 0.05). In the second period, the histological distribution showed an increase in frequency of basal cell carcinoma, from 2.1% to 4.7%, while the frequency of squamous cell carcinomas remained constant. Basal cell carcinoma no longer predominantly occurred in women, decreasing from 80% to 21.1% (P < 0.001). The distribution by gender of squamous cell carcinoma had become more equal due an increase in its frequency in women (P < 0.001). Frequency of tumours on lip mucosa and commissure had increased between the two periods (P < 0.004). CONCLUSIONS: The pattern of lip cancer reported to Public Hospitals of Madrid is changing: declining rates are noted since 2001-02. However, it is necessary to monitor these data to confirm the observed trends in future years. PMID- 26256569 TI - Is there any benefit from short-term perioperative antiepileptic prophylaxis in patients with chronic subdural haematoma? A retrospective controlled study. AB - BACKGROUND: Chronic subdural haematoma is a common pathology, which can be complicated by seizures. Seizures may worsen the outcome of patients presenting with a chronic subdural haematoma. However, since the overall and postoperative incidence of seizures and their impact on patients' outcome has been diversely appreciated in the literature, the interest of routine antiepileptic prophylaxis remains a controversial question. METHODS: We retrospectively investigated 99 patients who were surgically treated for a chronic subdural haematoma in two French academic hospitals: 48 patients received antiepileptic prophylaxis (group A) and were compared with a group of 51 patients who did not receive any antiepileptic prophylaxis (group B). Incidence of perioperative seizures was determined, and potential risk factors for epilepsy were analysed. RESULTS: Overall postoperative seizure incidence was 5.1%. There was a slight trend towards a lower incidence of seizures in patients who had received antiepileptic prophylaxis, but no significant difference was found between the two groups (4.2% in group A versus 5.9% in group B, P=0.697). Seizures were not correlated with increased death. No risk factor for seizures was identified. CONCLUSIONS: Our retrospective data showed there is no benefit of perioperative antiepileptic prophylaxis in patients surgically treated for chronic subdural haematoma. Since other authors have shown conflicting results, sufficiently powered prospective randomized study should be conducted in order to confirm these results. PMID- 26256570 TI - Duration of untreated psychosis and acute remission of negative symptoms in a South American first-episode psychosis cohort. AB - AIM: To determine the association between duration of untreated psychosis (DUP) and symptoms remission in a hospitalized first-episode psychosis cohort. METHODS: Inpatients with a first-episode non-affective psychosis were recruited. Subjects were divided into two groups of long and short DUP using a 3-month cut-off point, and this was related to remission at 10 weeks of treatment. Multivariate analyses were performed. RESULTS: Fifty-five inpatients were included. There were no differences in remission rates of positive symptoms. Up to 76.5% of the patients with a short DUP (<3 months) achieved remission of negative symptoms versus 31.6% in the DUP >= 3 months group (P = 0.003). After controlling for relevant factors, patients with a shorter DUP were still three times more likely to achieve negative symptoms remission (HR: 3.04, 95% CI 1.2-7.5). CONCLUSIONS: DUP is a prognostic factor that should be considered at an early stage to identify a 'high risk' subgroup of persistent negative symptoms. PMID- 26256571 TI - Tip-to-nucleus migration dynamics of the asexual development regulator FlbB in vegetative cells. AB - In Aspergillus nidulans, asexual differentiation requires the presence of the transcription factor FlbB at the cell tip and apical nuclei. Understanding the relationship between these two pools is crucial for elucidating the biochemical processes mediating conidia production. Tip-to-nucleus communication was demonstrated by photo-convertible FlbB::Dendra2 visualization. Tip localization of FlbB depends on Cys382 in the C-terminus and the bZIP DNA-binding domain in the N-terminus. FlbE, a critical FlbB interactor, binds the bZIP domain. Furthermore, the absence of FlbE results in loss of tip localization but not nuclear accumulation. flbE deletion also abrogates transcriptional activity indicating that FlbB gains transcriptional competence from interactions with FlbE at the tip. Finally, a bipartite nuclear localization signal is required for nuclear localization of FlbB. Those motifs of FlbB may play various roles in the sequence of events necessary for the distribution and activation of this transcriptionally active developmental factor. The tip accumulation, FlbE dependent activation, transport and nuclear import sketch out a process of relaying an environmentally triggered signal from the tip to the nuclei. As the first known instance of transcription factor-mediated tip-to-nucleus communication in filamentous fungi, this provides a general framework for analyses focused on elucidating the set of molecular mechanisms coupling apical signals to transcriptional events. PMID- 26256572 TI - Metabolomics-proteomics profiles delineate metabolic changes in kidney fibrosis disease. AB - Kidney fibrosis (KF) is a common process that leads to the progression of various types of kidney disease including kidney-yang deficiency syndrome, however, little is known regarding the underlying biology of this disorder. Fortunately, integrated omics approaches provide the molecule fingerprints related to the disease. In an attempt to address this issue, we integrated metabolomics proteomics profiles analyzed pathogenic mechanisms of KF based on rat model. A total 37 serum differential metabolites were contributed to KF progress, involved several important metabolic pathways. Using iTRAQ-based quantitative proteomics analysis, 126 differential serum proteins were identified and provide valuable insight into the underlying mechanisms of KF. These proteins appear to be involved in complement and coagulation cascades, regulation of actin cytoskeleton, MAPK signaling pathway, RNA transport, etc. Interestingly, pathway/network analysis of integrated proteomics and metabolomics data firstly reveals that these signaling pathways were closely related with KF. It further indicated that most of these proteins play a pivotal role in the regulation of metabolism pathways. PMID- 26256573 TI - Community-acquired Legionnaires' disease in a renal transplant recipient with unclear incubation period: the importance of molecular typing. AB - Transplant recipients are at risk of developing Legionnaires' disease (LD) because of impaired cellular immunity. Here, we describe a renal transplant recipient who developed LD at least 10 days after hospital admission and transplantation. The hospital water network was initially suspected, but further testing determined that the probable source was the patient's domestic water supply. Our report also suggests that the patient's immunosuppressed state may have switched potential colonization to pneumonia. PMID- 26256574 TI - Acute and chronic psychological stress as risk factors for cardiovascular disease: Insights gained from epidemiological, clinical and experimental studies. AB - Cardiovascular disease (CVD) remains a leading cause of death worldwide and identification and therapeutic modulation of all its risk factors is necessary to ensure a lower burden on the patient and on society. The physiological response to acute and chronic stress exposure has long been recognized as a potent modulator of immune, endocrine and metabolic pathways, however its direct implications for cardiovascular disease development, progression and as a therapeutic target are not completely understood. More and more attention is given to the bidirectional interaction between psychological and physical health in relation to cardiovascular disease. With atherosclerosis being a chronic disease starting already at an early age the contribution of adverse early life events in affecting adult health risk behavior, health status and disease development is receiving increased attention. In addition, experimental research into the biological pathways involved in stress-induced cardiovascular complications show important roles for metabolic and immunologic maladaptation, resulting in increased disease development and progression. Here we provide a concise overview of human and experimental animal data linking chronic and acute stress to CVD risk and increased progression of the underlying disease atherosclerosis. PMID- 26256575 TI - Small RNAs growing tall: miRNAs as drug targets in herpesvirus infections. AB - Herpesviruses establish life-long latent infections. They can cause severe morbidity and significant mortality particularly in immunocompromised hosts. Several are associated with cancers. Most express large amounts of microRNAs during latent or lytic infection. There is increasing evidence that these small RNA molecules play important roles in many aspects of pathogenesis, including lytic and latent infections, immune evasion and tumorigenesis. Therapies targeting microRNAs have already successfully made it into clinics, for example, to treat hepatitis C virus (HCV) infection. In this review, we will focus on regulatory functions of herpesvirus miRNAs that may be suitable for antiviral intervention. PMID- 26256576 TI - Enantioselective Synthesis of Carbo- and Heterocycles through a CuH-Catalyzed Hydroalkylation Approach. AB - The enantioselective, intramolecular hydroalkylation of halide-tethered styrenes has been achieved through a copper hydride-catalyzed process. This approach allowed for the synthesis of enantioenriched cyclobutanes, cyclopentanes, indanes, and six-membered N- and O-heterocycles. This protocol was applied to the synthesis of the commercial serotonin reuptake inhibitor (-)-paroxetine. PMID- 26256577 TI - Addressing barriers to emergency anaphylaxis care: from emergency medical services to emergency department to outpatient follow-up. AB - BACKGROUND: Anaphylaxis is a systemic life-threatening allergic reaction that presents unique challenges for emergency care practitioners. Allergists and emergency physicians have a history of collaborating to promote an evidence based, multidisciplinary approach to improve the emergency management and follow up of patients with or at risk of anaphylaxis. OBJECTIVES: To review recent scientific literature about anaphylaxis, discuss barriers to care, and recommend strategies to support improvement in emergency anaphylaxis care. METHODS: An expert panel of allergists and emergency physicians was convened by the American College of Allergy, Asthma and Immunology in November 2014 to discuss current knowledge about anaphylaxis, identify opportunities for emergency practitioners and allergists to partner to address barriers to care, and recommend strategies to improve medical management of anaphylaxis along the continuum of care: from emergency medical systems and emergency department practitioners for acute management through appropriate outpatient follow-up with allergists to confirm diagnosis, identify triggers, and plan long-term care. RESULTS: The panel identified key barriers to anaphylaxis care, including difficulties in making an accurate diagnosis, low rates of epinephrine administration during acute management, and inadequate follow-up. Strategies to overcome these barriers were discussed and recommendations made for future allergist/emergency physician collaborations, and key messages to be communicated to emergency practitioners were proposed. CONCLUSION: The panel recommended that allergists and emergency physicians continue to work in partnership, that allergists be proactive in outreach to emergency care practitioners, and that easy-to-access educational programs and materials be developed for use by emergency medical systems and emergency department practitioners in the training environment and in practice. PMID- 26256578 TI - Comparison of Angiographic Burden of Coronary Artery Disease in Patients With Versus Without Hepatitis C Infection. AB - Hepatitis C virus (HCV) infection is thought to be associated with an increased risk of coronary heart disease (CHD) events, perhaps secondary to increased inflammation. We sought to examine the angiographic burden of coronary artery disease (CAD) in patients with HCV compared to HCV-negative patients. All consecutive HCV RNA-positive patients (n = 61) who underwent coronary angiography at the University of Arkansas for Medical Sciences from 2001 to 2013 were identified. A parallel group of HCV-negative controls (n = 61), matched for age, gender, and indication for coronary angiography served as control. Angiographic burden of CAD was assessed by computing Gensini scores. Statistical analysis was performed using SPSS 21.0. Patients with HCV had significantly lower levels of total and low-density lipoprotein cholesterol. Preangiographic use of aspirin and statin was significantly lower in the HCV cohort. Number of patients with obstructive CAD was less in HCV group (23% vs 39%, p <0.05). However, angiographic Gensini score was similar in both groups. There was no correlation between HCV RNA titers and Gensini score (p = 0.9, analysis of variance). In conclusion, patients with active HCV infection have similar angiographic CAD burden as HCV-negative patients. Furthermore, viral load does not appear to correlate with atherosclerosis burden. Patients with HCV have less-obstructive CAD and less-frequent use of aspirin and statins. PMID- 26256580 TI - TV1 Taller than TV6. PMID- 26256579 TI - Comparison of Bleeding Outcomes After Percutaneous Coronary Intervention in Patients With Versus Without Aortic Stenosis. AB - Aortic stenosis (AS) is associated with an increased risk of bleeding, but little is known about the risk of bleeding during percutaneous coronary intervention (PCI) in patients with AS. In the era of transcutaneous aortic valve implantation, understanding the bleeding risks associated with AS is critical. This retrospective study included 7,926 patients who underwent PCI from 2004 to 2013. Patients were categorized according to the presence of significant AS: moderate or severe AS (n = 354) and mild or no AS (n = 7,572). The National Cardiovascular Data Registry (NCDR) definition of a bleeding event (transfusion, prolonged hospital stay, or decrease in hemoglobin >3.0 mg/dl) was used as the primary outcome, and the NCDR PCI Bleeding Risk Score was used to control for the underlying risk of bleeding because of baseline characteristics. Patients with AS had significantly higher NCDR PCI Bleeding Risk Scores and higher rates of bleeding events. Logistic regression showed that the NCDR PCI Bleeding Risk Score did predict bleeding outcomes. There was not, however, an independent association between AS and bleeding outcomes. The addition of AS to the risk score using net reclassification improvement did not enhance the model's ability to predict bleeding (p = 0.71). These data suggest that the NCDR PCI Bleeding Risk Score appropriately adjusts for bleeding risks in patients with AS. In conclusion, although patients with AS are more likely to have bleeding complications after PCI, the increased risk of bleeding is driven by the patients' baseline co morbidities rather than their AS. PMID- 26256581 TI - Effect of Echocardiographic Grading of Left Ventricular Diastolic Dysfunction by Different Classifications in Primary Care. AB - The presence of left ventricular (LV) diastolic dysfunction (DD) as characterized by Doppler echocardiography is associated with worse overall mortality both in symptomatic and asymptomatic patients. However, available data on this topic come from referral centers and have been obtained by different, validated algorithms for each single study. Thus, we aimed at determining the feasibility of comprehensive evaluation of LVDD in a primary care outpatient setting and at testing the concordance of different methodological approaches in grading diastolic dysfunction. Eight hundred eighty-five consecutive outpatients, in sinus rhythm, prospectively underwent Doppler echocardiography according to a predetermined protocol. Feasibility of each LV diastolic index and concordance between 3 methods to determine the degree of LVDD, namely the American Society of Echocardiography/European Association of Echocardiography (ASE/EAE) recommendations, the Olmstead County, and the Canberra Study protocols, were tested. Feasibility of all diastolic indexes was high, ranging from 93% of Valsalva maneuver to >=99% for mitral inflow and tissue Doppler parameters. Diastolic function was not classifiable in 6% to 19% of patients. The concordance for LV diastolic dysfunction degree was fair when comparing the classification of the ASE/EAE with those from Olmstead County (kappa = 0.25; reclassification rate 51%) and Canberra Study (kappa = 0.27; reclassification rate 43.7%), and was good for the comparison between the Olmstead County and Canberra classifications (kappa = 0.68, reclassification rate 27%). In conclusion, feasibility of LV diastolic function measurements is very high and grading diastolic dysfunction is possible in most patients in primary care settings. Substantial differences, however, exist when concordance is tested among 3 documented criteria, resulting in poor concordance of data interpretation and hence patient stratification and clinical management. PMID- 26256582 TI - Neuromelioidosis: Craniospinal MRI Findings in Burkholderia pseudomallei Infection. AB - PURPOSE: To investigate magnetic resonance imaging (MRI) findings of central nervous system (CNS) infection with Burkholderia pseudomallei. METHODS: Retrospective analysis of 10 patients (5 male and 5 female, age range from 13 to 69 years) with CNS melioidosis confirmed on culture of blood, sputum, cerebrospinal fluid, brain biopsy, and postmortem brain tissue. Clinical data were collected and MRI brain and/or spine were independently reviewed. RESULTS: Seven patients with brain parenchymal or intramedullary spinal cord lesions demonstrated rim-enhancing microabscesses with propensity for white matter tracts including the corticospinal tracts, corpus callosum, and cerebellar peduncles. Three of these 7 patients also showed thickening and enhancement of the trigeminal nerves with contiguous spread to brain stem trigeminal nuclei. Three patients had isolated extraaxial disease with findings including meningeal enhancement, extradural abscess, skull osteomyelitis, and scalp abscess. CONCLUSION: Spread of microabscesses along white matter tracts and frequent trigeminal nerve involvement are unique imaging characteristics of CNS melioidosis. These findings may provide insight into potential mechanisms for B. pseuodomallei entry into the CNS through direct axonal transport in cranial nerves bypassing the blood brain barrier. Prompt recognition of the neuroimaging features of this potentially fatal infection may allow for early microbiological culture and treatment. PMID- 26256584 TI - The signal pathway regulated by mitochondrial ATP-sensitive potassium channels might be involved in the mechanism of brain ischemic tolerance. PMID- 26256585 TI - Does interest broaden or narrow attentional scope? AB - Theory proposes that interest is a positive emotion that may either broaden attention to facilitate processing of new information, or narrow attention to preserve engagement with new information. To our knowledge, no research has directly examined the effect of interest on attentional scope. Across four experiments, we show that traits associated with the propensity to experience interest-specifically, trait curiosity and internal boredom proneness-are associated with a narrower scope of attention. We also find that, instead of broadening, interest actually narrows attentional scope in comparison to a neutral state and awe. Challenging the conventional notion that all positive emotions broaden cognition and attention, our findings suggest that specific emotions influence attention in ways that extend beyond a general emotional valence effect. PMID- 26256583 TI - How the cortico-thalamic feedback affects the EEG power spectrum over frontal and occipital regions during propofol-induced sedation. AB - Increasing concentrations of the anaesthetic agent propofol initially induces sedation before achieving full general anaesthesia. During this state of anaesthesia, the observed specific changes in electroencephalographic (EEG) rhythms comprise increased activity in the delta- (0.5-4 Hz) and alpha- (8-13 Hz) frequency bands over the frontal region, but increased delta- and decreased alpha activity over the occipital region. It is known that the cortex, the thalamus, and the thalamo-cortical feedback loop contribute to some degree to the propofol induced changes in the EEG power spectrum. However the precise role of each structure to the dynamics of the EEG is unknown. In this paper we apply a thalamo cortical neuronal population model to reproduce the power spectrum changes in EEG during propofol-induced anaesthesia sedation. The model reproduces the power spectrum features observed experimentally both in frontal and occipital electrodes. Moreover, a detailed analysis of the model indicates the importance of multiple resting states in brain activity. The work suggests that the alpha activity originates from the cortico-thalamic relay interaction, whereas the emergence of delta-activity results from the full cortico-reticular-relay cortical feedback loop with a prominent enforced thalamic reticular-relay interaction. This model suggests an important role for synaptic GABAergic receptors at relay neurons and, more generally, for the thalamus in the generation of both the delta- and the alpha- EEG patterns that are seen during propofol anaesthesia sedation. PMID- 26256586 TI - Synthesis, Characterization, Antimicrobial and Antitumor Activities of Sucrose Octa(N-ethyl)carbamate. AB - Sucrose octa(N-ethyl)carbamate was synthesized directly from sucrose and ethyl isocyanate, and its structure was confirmed by various analytical methods, such as (1)H and (13)C NMR, FTIR, m.p., MS, and optical rotation. Its antibacterial, antifungal and cytotoxic activities were investigated. It exhibited strong inhibition against all bacteria tested, namely S. aureus (MIC 0.18+/-0.006), B. cereus (MIC 0.094+/-0.000), M. flavus (MIC 0.28+/-0.01), L. monocytogenes (MIC 0.18+/-0.006), P. aeruginosa (MIC 0.094+/-0.002), S. typhimurium (MIC 0.094+/ 0.002), E. coli (MIC 0.18+/-0.006) and E. cloacae (MIC 0.18+/-0.006) and strong antifungal activity towards T. viride (MIC 0.09 +/- 0.006), A. versicolor (MIC 0.18 +/- 0.01), A. ochraceus (MIC 0.375 +/- 0.01) and P. ochrochloron (MIC 0.375 +/- 0.04). Furthermore, it showed moderate antitumor potential against human breast (GI50 357.20+/-14.12), colon (GI50 332.43+/-11.19) and cervical (GI50 282.67+/-3.97) cell lines and, more important, without hepatotoxicity. PMID- 26256587 TI - Investigation of the antimycobacterial activity of 8-hydroxyquinolines. AB - A series of styrylquinolines and quinolineamides based on the 8-hydroxyquinoline moiety were investigated as potential antimycobacterial agents. The lipophilicity of the compounds was measured using RP-HPLC and the tests of their activity against Mycobacterium kansasii, the M. avium complex, M. smegmatis, M. abscessus, M. tuberculosis and M. avium paratuberculosis was performed. Several of the compounds that were obtained appeared to be more effective than isoniazid and ciprofloxacin. The 5,7-dinitro-8-hydroxyquinoline derivative possessed the highest potency against M. abscessus and M. Smegmatis, which was about twice as effective as ciprofloxacin, while 2-(2-hydroxystyryl)-8-hydroxyquinoline-7 carboxylic acid appeared to be comparable with the standard drugs that are against the M. avium complex. The structure activity relationships are discussed. PMID- 26256588 TI - 2-Arylquinazolin-4(3H)-ones: Inhibitory Activities Against Xanthine Oxidase. AB - 2-Arylquinazolin-4(3H)-ones (1-25) were synthesized, and evaluated for their xanthine oxidase inhibitory activity. Significant to moderate activities were exhibited by the compounds 1-3, 7, 9, 13-15, 19-21, and 23 with IC50 between 2.80 - 28.13 uM as compared to the standard allopurinol (IC50 (IC50 = 2.01 +/- 0.01 uM). Compounds 4-6, 8, 11-12, 16-18, 22, and 24 demonstrated a weak activity with IC50 values 44.60 - 112.60 uM. Nonetheless, compounds 10 and 25 did not show any activity. Amongst all derivatives, compound 2, containing a C-4' dimethylamino group, was the most potent inhibitor of the enzyme with an IC50 value comparable to the standard. Kinetics studies on the most active compounds (2, 7, 9, 14, 15, 19, and 20) were conducted in order to determine their modes of inhibition and dissociation constants Ki. Some of the compounds of 2-arylquinazolin-4(3H)-one series were thus identified as potential leads for further studies towards the treatment of hyperuricemia and gout. PMID- 26256589 TI - Mechanical Modeling of the Human Cricoid Cartilage Using Computer-Aided Design: Applications in Airway Balloon Dilation Research. AB - OBJECTIVES: Balloon dilation is generally considered first-line treatment for airway stenosis. Some dilation systems utilize a compliant balloon that can conform around rigid structures. Others use a noncompliant balloon that does not conform, allowing for dilation of more rigid stenoses. We hypothesized that subglottic dilation with a noncompliant balloon increases the likelihood of fracture of the cricoid when compared to a compliant balloon. METHODS: Three fresh human cricoid cartilages were placed in a universal testing system to determine the expansile force necessary for cricoid fracture. Using these data, a 3D printer was used to construct a synthetic cricoid model possessing near identical physical characteristics to the human cricoid. Simulated dilation was then performed on the model using a compliant and a noncompliant balloon. RESULTS: Human cricoid fracture occurred at 97.25 N (SD = 8.34), and the synthetic cricoid model fractured at 100.10 N (SD = 7.32). Both balloons fractured the model in every replicate experiment. Mean balloon internal pressure at fracture was 7.67 ATM (SD = 1.21) for the compliant balloon and 11.34 ATM (SD = 1.29) for the noncompliant balloon. CONCLUSIONS: These data show that fracture of the cricoid is a valid concern in balloon dilation procedures where the balloon spans the subglottis. Furthermore, the hypothesis was rejected in that the compliant balloon system was at least as likely to fracture the cricoid model as the noncompliant. PMID- 26256590 TI - Natural course of subjects with elevated liver tests and normal liver histology. AB - BACKGROUND & AIMS: Liver biopsy (LB) is performed if non-invasive work-up of liver disease is inconclusive. The examination of liver tissue occasionally reveals normal histology. Long-term follow-up of such patients has not been performed. METHODS: We identified a total 70 subjects from our LB database with elevated liver tests and normal liver histology after a mean of 90.5 +/- 52.3 (range 15-216) months and conducted reassessment of medical history, physical examination, laboratory testing, ultrasound, transient elastography and LB if indicated. RESULTS: At follow-up examination, 15 (7 females (f)/8 males (m); 21.4%) subjects had normal liver tests and no further evidence of liver disease. A subset of 37 (29 f/8 m; 52.9%) subjects had persistently elevated liver tests without evidence indicating progressive liver disease but the cause thereof remained unexplained also at the follow-up visit. Three (0 f/3 m; 4.3%) subjects had consumed excessive alcohol with indicators of alcoholic liver disease. Eleven subjects (4 f/7 m; 15.7%) had developed steatosis on ultrasound examination along with weight gain and/or biochemical features of the metabolic syndrome. In addition, three (2 f/1 m) patients developed autoimmune hepatitis, one female presented with primary biliary cirrhosis. One male was diagnosed with cholangiocellular carcinoma 3 months after the initial evaluation. CONCLUSION: The clinical course of most patients was benign, but in approximately 20% of the subjects a liver disease developed. Particular attention should be given to autoimmune liver diseases in subjects with positive autoantibodies. In addition, lifestyle factors such as weight gain and alcohol consumption were associated with the manifestation of liver diseases. PMID- 26256591 TI - Carisoprodol - Effects on Human Performance and Behavior. AB - Carisoprodol, a commonly prescribed muscle relaxant, has adverse effects on human performance and is gaining recognition as a factor in driver impairment and accident causation. Carisoprodol is a centrally acting skeletal muscle relaxant indicated for the relief of musculoskeletal pain. Carisoprodol and its major metabolite meprobamate have central nervous system (CNS) sedating effects similar to benzodiazepines or alcohol. Following the ingestion of carisoprodol or meprobamate symptoms such as drowsiness, confusion, poor balance, and coordination are well documented in drivers, all of which are detrimental to human performance and driving ability. Although identified as a drug capable of producing decreased human performance, the full extent of carisoprodol and meprobamate's involvement in motor vehicle accidents and effect on driving skills may not be fully appreciated. This is due in part to the common co-administration of other CNS depressants, hypnotics, or narcotic drugs and the lack of routine testing for carisoprodol and meprobamate in the human performance toxicology laboratory. PMID- 26256592 TI - 3,4-Methylenedioxymethamphetamine - Effects on Human Performance and Behavior. AB - 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a unique drug, sharing properties of hallucinogens and stimulants. The acute effects of empathy, euphoria, and excitement for which it is used recreationally can make it overwhelmingly distracting for the user in the context of driving. This review considers the chemistry, synthesis, analysis, pharmacology, pharmacokinetics, and documented effects of MDMA on cognitive and psychomotor skills important to driving. Laboratory studies show that users do experience cognitive impairments, and may also act more impulsively while under the influence of the drug's sympathomimetic effects. Psychomotor impairment may occur with elevated doses or after repeated administration, and residual psychomotor impairment during the "coming-down" phase may be compounded by fatigue, dehydration, combined drug use, or other confounding factors. There is growing anecdotal information providing evidence of MDMA-impaired driving, and it is evident that many users recognize and attempt to mitigate the effects by delaying driving until the acute affects have dissipated. The drug inevitably may affect a subject's judgment and ability to properly assess their fitness to drive also. Blood concentrations in MDMA impaired drivers suggest that this impairment can be caused by normal patterns of recreational use, and MDMA use should be considered inconsistent with safe driving immediately following ingestion, and for up to a day or longer following use. PMID- 26256593 TI - Opioids - Effects on Human Performance and Behavior. AB - The purpose of the monograph is to provide readers with a summary of the literature relating selected opioids to performance issues, specifically driving. This monograph provides a summary of information to aid expert witnesses in preparing for court testimony. Information for codeine, hydrocodone, hydromorphone, methadone, morphine, and oxycodone is provided. In addition to a review of performance studies, a summary of acute and chronic pharmacology, pharmacokinetics, and metabolism is included. Opioids appear to impair psychomotor functioning likely to be important to the performance of complex, divided attention tasks such as driving. This impairment is notably more prevalent in individuals with no history of opioid use; individuals with long term opioid use do not demonstrate as extensive of an impairment. Other factors such as personality, environment, and pain control also sharply modulate opioid impairment. PMID- 26256594 TI - Phencyclidine - Effects on Human Performance and Behavior. AB - The history, symptoms, diagnosis and treatment of phencyclidine hydrochloride (PCP) intoxication, the pharmacology of PCP and the detection, identification and analysis of PCP are reviewed. The history of PCP from its synthesis in the early 1950s to the present is discussed. Intoxication with low to moderate doses of PCP resembles an acute, confusing state. High doses may cause serious neurological and cardiovascular complications and the patient is often comatose for several days. Treatment involves supportive psychological and medical measures, and acidification of the urine may further increase PCP clearance. The metabolism of PCP involves primarily hydroxylation followed by conjugation and elimination in the urine. Analysis can be accomplished by a number of instrumental methods, and several commercial test kits based on antigen-antibody interactions are available. PCP's effect on human performance and behaviour is due to its ability to alter the perception of reality in the user. PCP causes a range of effects that include hallucinations, delirium, disorientation, agitation, muscle rigidity, ataxia, nystagmus, seizures, and stupor. PCP has stimulant, depressant, hallucinogenic and analgesic effects. Which of these will be most pronounced is unpredictable and depends on the user's personality, psychological state and the environment of use. The impairment can manifest itself as over-aggressive or reckless driving behavior, or may mimic depressant effects due to PCP's anesthetic and depressant effect. PMID- 26256595 TI - Kinetic Study of the Intermolecular Interaction between 2-Phenoxypropionic Acid and beta-Bromo-cyclodextrin Affixed on the Stationary Phase by Liquid Chromatography. AB - The intermolecular interaction between 2-phenoxypropionic acid and beta-bromo cyclodextrin affixed on the stationary phase surface in a chiral HPLC system was studied by the moment analysis method. At first, pulse response and peak parking experiments were conducted to measure some parameters concerning the column geometry, adsorption equilibrium, and mass-transfer kinetics. Then, the first absolute moment (MU1) and second central moment (MU2') of the elution peaks were analyzed by the moment equations, which were developed by assuming that the reaction kinetics between the solute molecules and the functional ligands can be represented by the Langmuir-type rate equation. Finally, the flow-rate dependence of HETP calculated from MU1 and MU2' was analyzed by using the values of the parameters to determine the association and dissociation rate constants of the intermolecular interaction. It was demonstrated that the combination of the chromatographic experiments and moment analysis is one of the effective strategies for the kinetic study of intermolecular interactions. PMID- 26256596 TI - Highly Sensitive Determination of Ethylenediaminetetraacetic Acid Using a Permanganate Chemiluminescence System Catalyzed by Gold Nanoparticles. AB - A sensitive and selective chemiluminescence method was developed to determine ethylenediaminetetraacetic acid (EDTA) in water samples. It was observed that gold nanoparticles (AuNPs) catalyzed chemiluminescence (CL) reactions of permanganate-aldehydes which underwent an enhancement effect in the presence of iron(III) ions (Fe(3+)). This effect is more remarkable in the presence of EDTA, and a highly intensive CL emission is created in proportion to the EDTA concentration. These observations form the basis of the method for the high sensitive determination of EDTA in the 0.83 - 167 nmol L(-1) concentration range, with a detection limit of 0.25 nmol L(-1). The relative standard deviations for five repeated measurements of 5, 40 and 140 nmol L(-1) EDTA were 1.14, 2.48 and 0.65%, respectively. The method has good selectivity toward EDTA, and there are no interferences from other ions. The offered method has good precision, and was satisfactorily used for the sensitive determination of EDTA in water samples. PMID- 26256598 TI - Structural Transition of Bombyx mori Liquid Silk Studied with Vibrational Circular Dichroism Spectroscopy. AB - We investigated the structural transition from liquid silk to silk fibers with vibrational circular dichroism spectroscopy. Liquid silk showed a major right handed optically active band at around 1650 cm(-1) and a minor one at around 1680 cm(-1). The former disappeared over time, while the intensity in the latter increased. With the former wavenumber, liquid silk mainly adopted a random-coil structure. In contrast, the latter may reflect an intermediate structure in the transition. Furthermore, two right-handed bands at around 1630 and 1660 cm(-1) appeared with the disappearance of the major band, and then the wavenumber of the former shifted to around 1620 cm(-1). The shift results from the decrease in the frequency of the CO stretching mode due to the stacking of the beta-sheet that comprises fibers. The band at 1660 cm(-1) may reflect another intermediate structure due to its strong correlation with that at 1620 cm(-1) in terms of their temporal change in intensity. PMID- 26256597 TI - Simultaneous Online Measurement of H2O and CO2 in the Humid CO2 Adsorption/Desorption Process. AB - A dew point meter (DP) and an infrared (IR) CO2 analyzer were assembled in a humid CO2 adsorption/desorption system in series for simultaneous online measurements of H2O and CO2, respectively. The humidifier, by using surface flushing on a saturated brine solution was self-made for the generation of humid air flow. It was found that by this method it became relatively easy to obtain a low H2O content in air flow and that its fluctuation could be reduced compared to the bubbling method. Water calibration for the DP-IR detector is necessary to be conducted for minimizing the measurement error of H2O. It demonstrated that the relative error (RA) for simultaneous online measurements H2O and CO2 in the desorption process is lower than 0.1%. The high RA in the adsorption of H2O is attributed to H2O adsorption on the transfer pipe and amplification of the measurement error. The high accuracy of simultaneous online measurements of H2O and CO2 is promising for investigating their co-adsorption/desorption behaviors, especially for direct CO2 capture from ambient air. PMID- 26256599 TI - Determination of a N-Nitrosodimethylamine Precursor in Water Using Ultra-high Performance Liquid Chromatography-Tandem Mass Spectrometry. AB - 1,1,5,5-Tetramethylcarbohydrazide (TMCH) is the main precursor of N nitrosodimethylamine upon ozonation in the Yodo River basin, Japan. This study was performed to develop an analytical method for TMCH using solid-phase extraction with ultra-high performance liquid chromatography-tandem mass spectrometry. TMCH is hydrophilic and a tertiary amine derivative, so Oasis((r)) MCX cartridges were used as solid-phase cartridges. The recoveries of TMCH in tap and river waters as well as secondary effluent from a sewage treatment plant ranged from 75 to 94%. The limit of quantification of TMCH was 4 ng L(-1). The source of TMCH in the Yodo River basin was found to be effluent from one sewage treatment plant. The concentrations were < 4 ng L(-1) in raw water from water purification plants in regions other than the Yodo River basin, indicating that TMCH was used specifically in the basin. PMID- 26256600 TI - Detection of Several Carbohydrates Using Boron-doped Diamond Electrodes Modified with Nickel Hydroxide Nanoparticles. AB - In this work the electrooxidations of glucose, galactose, mannose, rhamnose, xylose and arabinose are studied at a nickel hydroxide nanoparticle modified boron-doped diamond electrode and compared to an unmodified electrode. These carbohydrates are very important in the second-generation ethanol production process. Nickel hydroxide modified boron-doped diamond was characterized by scanning electron microscopy and energy dispersive X-ray. Electrochemical impedance spectroscopy was employed to study the interface properties of surface modified electrodes in the absence and presence of the carbohydrates. Limits of detection were 5.3 * 10(-5), 6.8 * 10(-5), 2.7 * 10(-4), 6.9 * 10(-5), 8.8 * 10( 5) and 2.6 * 10(-5) mol L(-1) for glucose, galactose, mannose, rhamnose, arabinose, xylose, respectively. PMID- 26256601 TI - Development of Desolvation System for Single-cell Analysis Using Droplet Injection Inductively Coupled Plasma Atomic Emission Spectroscopy. AB - With a view to enhance the sensitivity of analytical instruments used in the measurement of trace elements contained in a single cell, we have now equipped the previously reported micro-droplet injection system (M-DIS) with a desolvation system. This modified M-DIS was coupled to inductively coupled plasma atomic emission spectroscopy (ICP-AES) and evaluated for its ability to measure trace elements. A flow rate of 100 mL/min for the additional gas and a measurement point -7.5 mm above the load coil (ALC) have been determined to be the optimal parameters for recording the emission intensity of the Ca(II) spectral lines. To evaluate the influence of the desolvation system, we recorded the emission intensities of the Ca(I), Ca(II), and H-beta spectral lines with and without inclusion of the desolvation system. The emission intensity of the H-beta spectral line reduces and the magnitude of the Ca(II)/Ca(I) emission intensity ratio increases four-fold with inclusion of the desolvation system. Finally, the elements Ca, Mg, and Fe present in a single cell of Pseudococcomyxa simplex are simultaneously determined by coupling the M-DIS equipped with the desolvation system to ICP-AES. PMID- 26256602 TI - A Novel Sensor for Sensitive and Selective Detection of Iodide Using Turn-on Fluorescence Graphene Quantum Dots/Ag Nanocomposite. AB - Based on the principle of fluorescence enhancing, by the strong and specific interreaction between iodide (I(-)) ions and nanoAg on the surface of graphene quantum dots/Ag (GQDs/Ag) nanocomposite, we propose a simple label-free and turn on method for the detection of I(-) ions with high selectivity and sensitivity by using fluorescent GQDs/Ag nanocomposite in aqueous media. PMID- 26256603 TI - Electrochemical Molecular Imprinted Sensors Based on Electrospun Nanofiber and Determination of Ascorbic Acid. AB - In this study, electrochemical molecularly imprinted sensors were fabricated and used for the determination of ascorbic acid (AA). Nanofiber membranes of cellulose acetate (CA)/multi-walled carbon nanotubes (MWCNTs)/polyvinylpyrrolidone (PVP) (CA/MWCNTs/PVP) were prepared by electrospinning technique. After being transferred to a glass carbon electrode (GC), the nanofiber interface was further polymerized with pyrrole through electrochemical cyclic voltammetry (CV) technique. Meanwhile, target molecules (such as AA) were embedded into the polypyrrole through the hydrogen bond. The effects of monomer concentration (pyrrole), the number of scan cycles and scan rates of polymerization were optimized. Differential pulse voltammetry (DPV) tests indicated that the oxidation current of AA (the selected target) were higher than that of the structural analogues, which illustrated the selective recognition of AA by molecularly imprinted sensors. Simultaneously, the molecularly imprinted sensors had larger oxidation current of AA than non imprinted sensors in the processes of rebinding. The electrochemical measurements showed that the molecularly imprinted sensors demonstrated good identification behavior for the detection of AA with a linear range of 10.0 - 1000 MUM, a low detection limit down to 3 MUM (S/N = 3), and a recovery rate range from 94.0 to 108.8%. Therefore, the electrochemical molecularly imprinted sensors can be used for the recognition and detection of AA without any time-consuming elution. The method presented here demonstrates the great potential for electrospun nanofibers and MWCNTs to construct electrochemical sensors. PMID- 26256604 TI - A Nicotinamide Adenine Dinucleotide Dispersed Multi-walled Carbon Nanotubes Electrode for Direct and Selective Electrochemical Detection of Uric Acid. AB - A nanocomposite platform built with multi-walled carbon nanotubes (MWCNTs) and nicotinamide adenine dinucleotide (NAD(+)) via a noncovalent interaction between the large pi systems in NAD(+) molecules and MWCNTs on a glassy carbon substrate was successfully developed for the sensitive and selective detection of uric acid (UA) in the presence of ascorbic acid (AA), dopamine (DA). NAD(+) has an adenine subunit and a nicotinamide subunit, which enabled interaction with the purine subunit of UA through a strong pi-pi interaction to enhance the specificity of UA. Compared with a bare glassy carbon electrode (GCE) and MWCNTs/GCE, the MWCNTs NAD(+)/GCE showed a low background current and a remarkable enhancement of the oxidation peak current of UA. Using differential pulse voltammetry (DPV), a high sensitivity for the determination of UA was explored for the MWCNTs-NAD(+) modified electrode. A linear relationship between the DPV peak current of UA and its concentration could be obtained in the range of 0.05 - 10 MUM with the detection limit as low as 10 nM (S/N = 3). This present strategy provides a novel and promising platform for the detection of UA in human urine and serum samples. PMID- 26256605 TI - Development of High-purity Certified Reference Materials for 17 Proteinogenic Amino Acids by Traceable Titration Methods. AB - To ensure the reliability of amino acid analyses, the National Metrology Institute of Japan of the National Institute of Advanced Industrial Science and Technology (NMIJ/AIST) has developed high-purity certified reference materials (CRMs) for 17 proteinogenic amino acids. These CRMs are intended for use as primary reference materials to enable the traceable quantification of amino acids. The purity of the present CRMs was determined based on two traceable methods: nonaqueous acidimetric titration and nitrogen determination by the Kjeldahl method. Since neither method could distinguish compounds with similar structures, such as amino acid-related impurities, impurities were thoroughly quantified by combining several HPLC methods, and subtracted from the obtained purity of each method. The property value of each amino acid was calculated as a weighted mean of the corrected purities by the two methods. The uncertainty of the property value was obtained by combining measurement uncertainties of the two methods, a difference between the two methods, the uncertainty from the contribution of impurities, and the uncertainty derived from inhomogeneity. The uncertainty derived from instability was considered to be negligible based on stability monitoring of some CRMs. The certified value of each amino acid, property value with uncertainty, was given for both with or without enantiomeric separation. PMID- 26256606 TI - A Catalytic DNA Probe with Stem-loop Motif for Human T47D Breast Cancer Cells. AB - In vitro selection methods allow for isolation of DNAzymes (catalytic DNAs) from random DNA pools. Here we describe a fluorogenic DNAzyme, LYF5, isolated using a double-random selection approach: a random DNA pool was selected against a complex molecular mixture derived from a breast cancer cell line, T47D. LYF5 specifically indicates the T47D breast cancer cell line with high sensitivity. After sequence optimization, the second-generation DNAzyme, 2G-LYF5, exhibited an approximately 2-fold higher cleavage percentage. Finally, we have determined that the intramolecular stem-loop motif plays a crucial role in 2G-LYF5 activity. Our findings underscore the capability of single-stranded DNA molecules to perform highly sophisticated functions that are amenable to the development of diagnostic tests for early identification of breast cancer. PMID- 26256607 TI - Multi-residue Method for Determination of Selected Neonicotinoid Insecticides in Traditional Chinese Medicine Using Modified Dispersive Solid-phase Extraction Combined with Ultra-performance Liquid Chromatography Tandem Mass Spectrometry. AB - A reliable and cost-effective method for the determination of multiple neonicotinoids was developed using a modified QuEChERS-based extraction procedure in complex matrices, namely Hedyotis diffusa (a representative of the Traditional Chinese herb which contains lots of pigment, saponin and terpene) and Semifluid extract of deer foetus (a representative of the Chinese traditional patent medicine that was produced with several different herbs, and especially containing lots of protein, except for other interference components). Ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was used for the quantification and confirmation of five compounds. Except for two transitions obtained by the MRM mode, identification was further carried out by the ion radios. The proposed chemical structure of every selected product ion and the proposed pyrolysis way were presented. The extraction, clean-up, UPLC separation and MS/MS parameters were especially optimized in order to obtain better recoveries. The low limits of detection (LODs) of five insecticides ranged from 0.04 to 0.81 MUg kg(-1). Matrix matched calibration in the concentration range of 0.05 - 50 MUg kg(-1) were used to compensate the matrix effect, and reasonable recoveries 80.2 - 105.4% of five compounds were demonstrated in different spiked levels with inter-RSD from 1.7 to 10.6%. The proposed method is an alternative approach to make an analysis of neonicotinoids in Chinese medicine, which is more reliable and promising compared with other detection methods. PMID- 26256608 TI - Simultaneous Determination of Trigonelline, Caffeine, Chlorogenic Acid and Their Related Compounds in Instant Coffee Samples by HPLC Using an Acidic Mobile Phase Containing Octanesulfonate. AB - In order to analyze trigonelline, caffeine, chlorogenic acid, and their related compounds simultaneously, an HPLC method using an InertSustain C18 column and a mobile phase containing octanesulfonate as an ion-pairing reagent under an acidic condition was developed. The optimum mobile phase conditions were determined to be 0.1% phosphoric acid, 4 mM octanesulfonate, and 15% methanol at 35 degrees C. Using the proposed method, trigonelline, nicotinic acid, caffeine, theophylline, chlorogenic acid, and caffeic acid in ten instant coffee samples were analyzed. These analytes except for theophylline were detected in all samples. An increase in the caffeine content in instant coffee samples tended to decrease in both trigonelline and chlorogenic acid contents, and the trigonelline content was found to be correlated well with the chlorogenic acid content (R(2) = 0.887). PMID- 26256609 TI - Comparative Studies on Effects of Acid Solutions on Aquatic Plants by Beam Deflection and Absorbance Spectroscopy Methods. AB - The beam deflection method and absorbance spectroscopy were applied to study effects of acid solutions on aquatic plants, and their results were compared. Aquatic plants Egeria densa and Ceratophyllum demersum L were used as model plants. In absorbance experiments, a piece of the plants was put in a beaker with 20 mL HCl solution, and absorbance of the HCl solution was measured every 30 min. In beam deflection experiments, a probe beam from a He-Ne laser was focused to a vicinity of the plants in a culture dish with HCl solution by an objective lens, and deflection signals of the probe beam were monitored by a position sensor. Absorbance spectra of the HCl solutions with immersing of the plants showed absorbance below 410 nm, suggesting that some compounds leaked from the plants into the HCl solutions. Changes of absorbance and deflection signals with immersion time were examined for different pH levels. The changing trends of the absorbance and deflection signals with time were similar, but the absorbance changes were delayed for about 2 - 3 h. The absorbance method could not detect the effect of the pH 5.0 HCl solutions on the aquatic plants, while the deflection method could. PMID- 26256610 TI - Retention Behavior of Halogenated Benzenes on a Stationary Phase Having a 2,4 Dibromophenoxy Group as the Halogen Recognition Functional Group. AB - A stationary phase with a dipole interaction was synthesized by immobilizing the 2,4-dibromophenoxy (DBP) group onto a hydrophilic base resin. The chromatographic properties for halogenated benzenes were evaluated on the DBP-resin by reversed phase mode. The separation efficiency of the DBP-resin for p-xylene and 1,4 dihalogenated benzenes was better than that of the column packed with octadecylsilane (ODS). The results suggested that the retention of the solutes on the DBP-resin depends on the Debye interaction in addition to with the dispersion force caused by the DBP group. PMID- 26256611 TI - Evaluation of the Effect on Temperature Conversion of pHT at 25 degrees C in the Temperature Range 0 - 40 degrees C Due to Incorrect Estimations of Salinity, Alkalinity, and Phosphate and Silicate Concentrations. AB - Under conditions where carbonate and oceanic parameters such as alkalinity (A(T)), salinity (Sp), and phosphate (P(T)) and silicate (SiT) concentrations cannot be obtained, the use of fixed values to calculate total pH (pHT) at 25 degrees C was demonstrated. For temperatures of 20 - 30 degrees C, these values caused a maximum error of +/-0.001 in pHT. For temperatures of 0 - 40 degrees C, using fixed values with correct SP values caused a maximum error of approximately +0.0021. PMID- 26256612 TI - Weight-based Synthesized Standards Preparation for Correction-free Calibration in X-ray Fluorescence Determination of Tungsten in High-speed Steel. AB - This paper suggests a correction-free calibration method in wavelength dispersive X-ray fluorescence analysis in order to determine tungsten as a major alloyed element in high-speed steels accurately. Matrix effects on fluorescent X-ray intensity of tungsten Lalpha line were minimized by borate fusion, and the total amount of tungsten in the glassy matrix could be quantified. Glass bead specimens were prepared with 10 to 12 mg of the steel sample and 4.0 g of lithium tetraborate as a flux agent. Without untraceable X-ray intensity correction, a linear calibration curve was obtained by measuring synthesized calibration standards prepared by using standard solutions. As compared with fundamental parameter calculations, the present method gave more accurate results of tungsten in certified reference materials of high-speed steel. PMID- 26256613 TI - Effect of Long-time X-ray Irradiation on Cr and Hg in a Polypropylene Disk Certified Reference Material Observed during Measurements by X-ray Fluorescence Spectrometry. AB - The effect of long-time X-ray irradiation on Cr and Hg in a polypropylene disk certified reference material (PP disk CRM, NMIJ CRM 8136-a) during measurements by X-ray fluorescence (XRF) spectrometry was examined in the present study. The XRF intensities of Cr (Kalpha), Hg (Lalpha) and Pb (Lalpha), obtained by an energy-dispersive (ED)-XRF spectrometer, showed the different intensity trends and the obtained XRF intensity ratios of Cr/Pb and Hg/Pb revealed decreasing and constant ratios, respectively, for long-time X-ray irradiation of up to 430 h. A similar decreasing trend of the Cr/Pb intensity ratio was also observed by wavelength-dispersive (WD)-XRF measurements for 120 h. Moreover, Cr, Hg and Pb in the PP disks obtained after long-time measurements by the WD-XRF spectrometer were measured by an ED-XRF spectrometer, and the loss of Cr was confirmed. From these results, Cr in the PP disk CRM, whose chemical form was an organometallic compound, was considered to be possibly lost during the XRF analysis for long time or frequent measurements. PMID- 26256615 TI - Erratum: Analytical Sciences, 2015, Vol. 31, No. 6, p. 481. Photoluminescent Detection of Nitrite with Carbon Nanodots Prepared by Microwave-assisted Synthesis. PMID- 26256616 TI - Letter to the editor regarding Bilotta et al. 2014 Diagnostic work up for language testing in patients undergoing awake craniotomy for brain lesions in language areas. PMID- 26256618 TI - Involving religious leaders in HIV care and treatment at a university-affiliated hospital in Ethiopia: Application of formative inquiry. AB - In sub-Saharan Africa, religious views strongly influence how people relate to illness, health, and healing. Belief in the curative power of religion, including for HIV, persists in many communities. As such, many funding agencies and organisations working in the field of HIV have incorporated religious institutions into their programmes in various capacities. Yet, debate continues regarding the benefits and drawbacks of including sectarian organisations in the fight against HIV. In the current study, we sought to explore whether patients with HIV would be amenable to receiving HIV-related psychosocial support from religious leaders. We interviewed 48 Ethiopian Orthodox Church followers who presented for routine HIV care at Gondar University Hospital ART (antiretroviral treatment) clinic. Although almost half (46%) of participants self-identified as 'very religious', the majority of them (73%) had not disclosed their HIV status to a religious leader. Study participants highlighted multiple factors that could potentially affect their willingness to involve religious leaders in their HIV care. We discuss these findings in relation to religion and HIV in the African context. Our findings support the use of formative qualitative work prior to developing and implementing programmes that integrate faith and medical communities. PMID- 26256619 TI - Effect of sports bra type and gait speed on breast discomfort, bra discomfort and perceived breast movement in Chinese women. AB - This study investigated the effect of sports bra type (encapsulation versus compression) and gait speed on perceptions of breast discomfort, bra discomfort and breast movement reported by Chinese women. Visual analogue scales were used to evaluate breast discomfort, bra component discomfort and perceived breast movement of 21 Chinese participants when they wore an encapsulation or a compression sports bra, while static and while exercising at three different gait speeds. Participants perceived less breast discomfort and breast movement when wearing a compression bra compared to an encapsulation bra at a high gait speed, suggesting that compression bras are likely to provide the most effective support for Chinese women. However, significantly higher bra discomfort was perceived in the compression bra compared to the encapsulation bra when static and at the lower gait speed, implying that ways to modify the design of sports bras, particularly the straps, should be investigated to provide adequate and comfortable breast support. PRACTITIONER SUMMARY: The compression sports bra provided more comfortable support than the encapsulation sports bra for these Chinese women when running on a treadmill. However, these women perceived higher bra discomfort when wearing the compression bra when stationary. Further research is needed to modify the design of sports bras, particularly the straps, to provide adequate and comfortable breast support. PMID- 26256620 TI - Total synthesis of the natural product EBC-329. AB - The first total synthesis of an anti-leukemic diterpene natural product EBC-329 (1) has been accomplished starting from readily available 6,6-dimethyl-3 oxabicyclo[3.1.0]hexane-2,4-dione (7). An efficient and general approach has been reported for the synthesis of EBC-329 in 13 steps with an overall yield of 10%. PMID- 26256622 TI - Monte Carlo simulations of the secondary neutron ambient and effective dose equivalent rates from surface to suborbital altitudes and low Earth orbit. AB - Occupational exposures from ionizing radiation are currently regulated for airline travel (<20 km) and for missions to low-Earth orbit (~300-400 km). Aircrew typically receive between 1 and 6 mSv of occupational dose annually, while aboard the International Space Station, the area radiation dose equivalent measured over just 168 days was 106 mSv at solar minimum conditions. It is anticipated that space tourism vehicles will reach suborbital altitudes of approximately 100 km and, therefore, the annual occupational dose to flight crew during repeated transits is expected to fall somewhere between those observed for aircrew and astronauts. Unfortunately, measurements of the radiation environment at the high altitudes reached by suborbital vehicles are sparse, and modelling efforts have been similarly limited. In this paper, preliminary MCNPX radiation transport code simulations are developed of the secondary neutron flux profile in air from surface altitudes up to low Earth orbit at solar minimum conditions and excluding the effects of spacecraft shielding. These secondary neutrons are produced by galactic cosmic radiation interacting with Earth's atmosphere and are among the sources of radiation that can pose a health risk. Associated estimates of the operational neutron ambient dose equivalent, used for radiation protection purposes, and the neutron effective dose equivalent that is typically used for estimates of stochastic health risks, are provided in air. Simulations show that the neutron radiation dose rates received at suborbital altitudes are comparable to those experienced by aircrew flying at 7 to 14 km. We also show that the total neutron dose rate tails off beyond the Pfotzer maximum on ascension from surface up to low Earth orbit. PMID- 26256623 TI - Use of micro-computed tomography to evaluate the effects of exercise on preventing the degeneration of articular cartilage in tail-suspended rats. AB - Space flight has been shown to induce bone loss and muscle atrophy, which could initiate the degeneration of articular cartilage. Countermeasures to prevent bone loss and muscle atrophy have been explored, but few spaceflight or ground-based studies have focused on the effects on cartilage degeneration. In this study, we investigated the effects of exercise on articular cartilage deterioration in tail suspended rats. Thirty-two female Sprague-Dawley rats were randomly divided into four groups (n=8 in each): tail suspension (TS), tail suspension plus passive motion (TSP), tail suspension plus active exercise (TSA), and control (CON) groups. In the TS, TSP, and TSA groups, the rat hindlimbs were unloaded for 21 days by tail suspension. Next, the cartilage thickness and volume, and the attenuation coefficient of the distal femur were evaluated by micro-computed tomography (MUCT). Histological analysis was used to assess the surface integrity of the cartilage, cartilage thickness, and chondrocytes. The results showed that: (1) the cartilage thickness on the distal femur was significantly lower in the TS and TSP groups compared with the CON and TSA groups; (2) the cartilage volume in the TS group was significantly lower compared with the CON, TSA, and TSP groups; and (3) histomorphology showed that the chondrocytes formed clusters where the degree of matrix staining was lower in the TS and TSP groups. There were no significant differences between any of these parameters in the CON and TSA groups. The cartilage thickness measurements obtained by MUCT and histomorphology correlated well. In general, tail suspension could induce articular cartilage degeneration, but active exercise was effective in preventing this degeneration in tail-suspended rats. PMID- 26256624 TI - Dermatopathology effects of simulated solar particle event radiation exposure in the porcine model. AB - The space environment exposes astronauts to risks of acute and chronic exposure to ionizing radiation. Of particular concern is possible exposure to ionizing radiation from a solar particle event (SPE). During an SPE, magnetic disturbances in specific regions of the Sun result in the release of intense bursts of ionizing radiation, primarily consisting of protons that have a highly variable energy spectrum. Thus, SPE events can lead to significant total body radiation exposures to astronauts in space vehicles and especially while performing extravehicular activities. Simulated energy profiles suggest that SPE radiation exposures are likely to be highest in the skin. In the current report, we have used our established miniature pig model system to evaluate the skin toxicity of simulated SPE radiation exposures that closely resemble the energy and fluence profile of the September, 1989 SPE using either conventional radiation (electrons) or proton simulated SPE radiation. Exposure of animals to electron or proton radiation led to dose-dependent increases in epidermal pigmentation, the presence of necrotic keratinocytes at the dermal-epidermal boundary and pigment incontinence, manifested by the presence of melanophages in the derm is upon histological examination. We also observed epidermal hyperplasia and a reduction in vascular density at 30 days following exposure to electron or proton simulated SPE radiation. These results suggest that the doses of electron or proton simulated SPE radiation results in significant skin toxicity that is quantitatively and qualitatively similar. Radiation-induced skin damage is often one of the first clinical signs of both acute and non-acute radiation injury where infection may occur, if not treated. In this report, histopathology analyses of acute radiation-induced skin injury are discussed. PMID- 26256625 TI - Assessment of polycarbonate filter in a molecular analytical system for the microbiological quality monitoring of recycled waters onboard ISS. AB - On the ISS, as on Earth, water is an essential element for life and its quality control on a regular basis allows to ensure the health of the crew and the integrity of equipment. Currently, microbial water analysis onboard ISS still relies on the traditional culture-based microbiology methods. Molecular methods based on the amplification of nucleic acids for microbiological analysis of water quality show enormous potential and are considered as the best alternative to culture-based methods. For this reason, the Midass, a fully integrated and automated prototype was designed conjointly by ESA and bioMerieux for a rapid monitoring of the microbiological quality of air. The prototype allows air sampling, sample processing and the amplification/detection of nucleic acids. We describe herein the proof of principle of an analytical approach based on molecular biology that could fulfill the ESA's need for a rapid monitoring of the microbiological quality of recycled water onboard ISS. Both concentration and recovery of microorganisms are the main critical steps when the microfiltration technology is used for water analysis. Among filters recommended standards for monitoring the microbiological quality of the water, the polycarbonate filter was fully in line with the requirements of the ISO 7704-1985 standard in terms of efficacy of capture and recovery of bacteria. Moreover, this filter does not retain nucleic acids on the surface and has no inhibitory effect on their downstream processing steps such as purification and amplification/detection. Although the Midass system was designed for the treatment of air samples, the first results on the integration of PC filters were encouraging. Nevertheless, system modifications are needed to better adapt the Midass system for the monitoring of the microbiological water quality. PMID- 26256627 TI - Modeling snail breeding in a bioregenerative life support system. AB - The discrete-time model of snail breeding consists of two sequentially linked submodels: "Stoichiometry" and "Population". In both submodels, a snail population is split up into twelve age groups within one year of age. The first submodel is used to simulate the metabolism of a single snail in each age group via the stoichiometric equation; the second submodel is used to optimize the age structure and the size of the snail population. Daily intake of snail meat by crewmen is a guideline which specifies the population productivity. The mass exchange of the snail unit inhabited by land snails of Achatina fulica is given as an outcome of step-by-step modeling. All simulations are performed using Solver Add-In of Excel 2007. PMID- 26256626 TI - Nitric oxide-mediated bystander signal transduction induced by heavy-ion microbeam irradiation. AB - In general, a radiation-induced bystander response is known to be a cellular response induced in non-irradiated cells after receiving bystander signaling factors released from directly irradiated cells within a cell population. Bystander responses induced by high-linear energy transfer (LET) heavy ions at low fluence are an important health problem for astronauts in space. Bystander responses are mediated via physical cell-cell contact, such as gap-junction intercellular communication (GJIC) and/or diffusive factors released into the medium in cell culture conditions. Nitric oxide (NO) is a well-known major initiator/mediator of intercellular signaling within culture medium during bystander responses. In this study, we investigated the NO-mediated bystander signal transduction induced by high-LET argon (Ar)-ion microbeam irradiation of normal human fibroblasts. Foci formation by DNA double-strand break repair proteins was induced in non-irradiated cells, which were co-cultured with those irradiated by high-LET Ar-ion microbeams in the same culture plate. Foci formation was suppressed significantly by pretreatment with an NO scavenger. Furthermore, NO-mediated reproductive cell death was also induced in bystander cells. Phosphorylation of NF-kappaB and Akt were induced during NO-mediated bystander signaling in the irradiated and bystander cells. However, the activation of these proteins depended on the incubation time after irradiation. The accumulation of cyclooxygenase-2 (COX-2), a downstream target of NO and NF kappaB, was observed in the bystander cells 6 h after irradiation but not in the directly irradiated cells. Our findings suggest that Akt- and NF-kappaB-dependent signaling pathways involving COX-2 play important roles in NO-mediated high-LET heavy-ion-induced bystander responses. In addition, COX-2 may be used as a molecular marker of high-LET heavy-ion-induced bystander cells to distinguish them from directly irradiated cells, although this may depend on the time after irradiation. PMID- 26256628 TI - A protective role of HSP90 chaperone in gamma-irradiated Arabidopsis thaliana seeds. AB - The heat shock protein 90 (HSP90) is required for the maturation and conformational regulation of many regulatory proteins affecting morphogenetic pathways and stress tolerance. The purpose of this work is to disclose a role of HSP90 in radioresistance of seeds. Arabidopsis thaliana (Ler) seeds were exposed to gamma-ray irradiation with doses of 0.1-1 kGy using (60)Co source to obtain a viable but polymorphic material. A comet assay of the seeds showed a dose dependent increase in DNA damage. Phenotypic consequences of irradiation included growth stimulation at doses of 0.1-0.25 kGy and negative growth effects at doses from 0.5 kGy and beyond, along with increasing heterogeneity of seedling growth rate and phenotype. The frequencies of abnormal phenotypes were highly correlated with the degree of DNA damage in seeds. Treatment of seeds with geldanamycin (GDA), an inhibitor of HSP90, stimulated the seedling growth at all radiation doses and, at the same time, enhanced the growth rate and morphological diversity. It was also found that HSP70 induction by gamma-rays was increased following GDA treatment (shown at 1 kGy). We suppose that the GDA-induced HSP70 can be involved in elimination of detrimental radiation effects that ultimately results in growth stimulation. On the other hand, the increase in phenotypic variation, when HSP90 function was impaired, confirms the supposition that the chaperone may control the concealment of cryptic genetic alterations and the developmental stability. In general, these results demonstrate that HSP90 may interface the stress response and phenotypic expression of genetic alterations induced by irradiation. PMID- 26256629 TI - Developmental, nutritional and hormonal anomalies of weightlessness-grown wheat. AB - The behavior of water in weightlessness, as occurs in orbiting spacecraft, presents multiple challenges for plant growth. Soils remain saturated, impeding aeration, and leaf surfaces remain wet, impeding gas exchange. Herein we report developmental and biochemical anomalies of "Super Dwarf" wheat (Triticum aestivum L.) grown aboard Space Station Mir during the 1996-97 "Greenhouse 2" experiment. Leaves of Mir-grown wheat were hyperhydric, senesced precociously and accumulated aromatic and branched-chain amino acids typical of tissues experiencing oxidative stress. The highest levels of stress-specific amino acids occurred in precociously-senescing leaves. Our results suggest that the leaf ventilation system of the Svet Greenhouse failed to remove sufficient boundary layer water, thus leading to poor gas exchange and onset of oxidative stress. As oxidative stress in plants has been observed in recent space-flight experiments, we recommend that percentage water content in apoplast free-spaces of leaves be used to evaluate leaf ventilation effectiveness. Mir-grown plants also tillered excessively. Crowns and culms of these plants contained low levels of abscisic acid but high levels of cytokinins. High ethylene levels may have suppressed abscisic acid synthesis, thus permitting cytokinins to accumulate and tillering to occur. PMID- 26256630 TI - A semiconductor radiation imaging pixel detector for space radiation dosimetry. AB - Progress in the development of high-performance semiconductor radiation imaging pixel detectors based on technologies developed for use in high-energy physics applications has enabled the development of a completely new generation of compact low-power active dosimeters and area monitors for use in space radiation environments. Such detectors can provide real-time information concerning radiation exposure, along with detailed analysis of the individual particles incident on the active medium. Recent results from the deployment of detectors based on the Timepix from the CERN-based Medipix2 Collaboration on the International Space Station (ISS) are reviewed, along with a glimpse of developments to come. Preliminary results from Orion MPCV Exploration Flight Test 1 are also presented. PMID- 26256631 TI - Group dynamics challenges: Insights from Biosphere 2 experiments. AB - Successfully managing group dynamics of small, physically isolated groups is vital for long duration space exploration/habitation and for terrestrial CELSS (Controlled Environmental Life Support System) facilities with human participants. Biosphere 2 had important differences and shares some key commonalities with both Antarctic and space environments. There were a multitude of stress factors during the first two year closure experiment as well as mitigating factors. A helpful tool used at Biosphere 2 was the work of W.R. Bion who identified two competing modalities of behavior in small groups. Task oriented groups are governed by conscious acceptance of goals, reality-thinking in relation to time and resources, and intelligent management of challenges. The opposing unconscious mode, the "basic-assumption" ("group animal") group, manifests through Dependency/Kill the Leader, Fight/Flight and Pairing. These unconscious dynamics undermine and can defeat the task group's goal. The biospherians experienced some dynamics seen in other isolated teams: factions developing reflecting personal chemistry and disagreements on overall mission procedures. These conflicts were exacerbated by external power struggles which enlisted support of those inside. Nevertheless, the crew evolved a coherent, creative life style to deal with some of the deprivations of isolation. The experience of the first two year closure of Biosphere 2 vividly illustrates both vicissitudes and management of group dynamics. The crew overrode inevitable frictions to creatively manage both operational and research demands and opportunities of the facility, thus staying 'on task' in Bion's group dynamics terminology. The understanding that Biosphere 2 was their life support system may also have helped the mission to succeed. Insights from the Biosphere 2 experience can help space and remote missions cope successfully with the inherent challenges of small, isolated crews. PMID- 26256632 TI - Fluorescent minerals--A potential source of UV protection and visible light for the growth of green algae and cyanobacteria in extreme cosmic environments. AB - We propose that green algae (Chlorella variabilis and Dunaliella tertiolecta) and cyanobacteria (Synechococcus elongatus and Nostoc commune) can grow inside fluorescent rock minerals which convert damaging UV light to visible light, thereby allowing these organisms to survive and thrive in UV-rich environments without (or with limited) visible light, which would otherwise be inimical to them. The four microorganisms were incubated inside fluorescent rocks composed of fluorite, calcite and pyrite. The resultant growth was then measured following exposure to UV radiation, with the use of optical density and measurement of chlorophyll concentration. Results show that the microorganisms were shielded from harmful UV in these semi-transparent rocks, while at the same time benefiting from the fact that the minerals converted UV to visible light; this have been shown by a statistically significant increase in their growth, which although lower than when the cells were incubated in sunlight, was significantly higher than in controls incubated in the dark. PMID- 26256633 TI - Concepts and challenges in cancer risk prediction for the space radiation environment. AB - Cancer is an important long-term risk for astronauts exposed to protons and high energy charged particles during travel and residence on asteroids, the moon, and other planets. NASA's Biomedical Critical Path Roadmap defines the carcinogenic risks of radiation exposure as one of four type I risks. A type I risk represents a demonstrated, serious problem with no countermeasure concepts, and may be a potential "show-stopper" for long duration spaceflight. Estimating the carcinogenic risks for humans who will be exposed to heavy ions during deep space exploration has very large uncertainties at present. There are no human data that address risk from extended exposure to complex radiation fields. The overarching goal in this area to improve risk modeling is to provide biological insight and mechanistic analysis of radiation quality effects on carcinogenesis. Understanding mechanisms will provide routes to modeling and predicting risk and designing countermeasures. This white paper reviews broad issues related to experimental models and concepts in space radiation carcinogenesis as well as the current state of the field to place into context recent findings and concepts derived from the NASA Space Radiation Program. PMID- 26256634 TI - From the desk of the Editor-in-Chief. PMID- 26256636 TI - FRET versus PET: ratiometric chemosensors assembled from naphthalimide dyes and crown ethers. AB - Novel bi-chromophoric naphthalimide derivatives containing benzo-15-crown-5 and N phenyl-aza-15-crown-5 receptor moieties BNI2 and BNI3 were designed and prepared. Significant Forster resonance energy transfer (FRET) from donor (D) amido naphthalimide to acceptor (A) amino-naphthalimide chromophores as well as photoinduced electron transfer (PET) between the N-aryl receptor and amido naphthalimide fragment was revealed by the steady-state and time-resolved UV/Vis absorption and fluorescence spectroscopy. Upon the addition of alkaline-earth metal perchlorates to an acetonitrile solution of ligands, FRET mediated fluorescence enhancement was observed, which was a result of inhibition of the PET competitive deactivation pathway. The studied compounds provide an opportunity to register a two-channel fluorescence response upon selective excitation of either of the photoactive units and, thus, might be of interest as ratiometric probes. PMID- 26256635 TI - Traumatic brain injuries and computed tomography use in pediatric sports participants. AB - BACKGROUND: Childhood sports-related head trauma is common, frequently leading to emergency department (ED) visits. We describe the spectrum of these injuries and trends in computed tomography (CT) use in the Pediatric Emergency Care Applied Research Network. METHODS: This was a secondary analysis of a large prospective cohort of children with head trauma in 25 Pediatric Emergency Care Applied Research Network EDs between 2004 and 2006. We described and compared children 5 to 18 years old by CT rate, traumatic brain injury (TBI) on CT, and clinically important TBI (ciTBI). We used multi-variable logistic regression to compare CT rates, adjusting for clinical severity. Outcomes included frequency of CT, TBIs on CT, and ciTBIs (defined by [a] death, [b] neurosurgery, [c] intubation>24 hours, or [d] hospitalization for >=2 nights). FINDINGS: A total of 3289 (14%) of 23082 children had sports-related head trauma. Two percent had Glasgow Coma Scale scores less than 14. 53% received ED CTs, 4% had TBIs on CT, and 1% had ciTBIs. Equestrians had increased adjusted odds (1.8; 95% confidence interval [CI], 1.0 3.0]) of CTs; the rate of TBI on CT was 4% (95% CI, 3%-5%). Compared with team sports, snow (adjusted odds ratio, 4.1; 95% CI 1.5-11.4) and nonmotorized wheeled (adjusted odds ratio, 12.8; 95% CI, 5.5-32.4) sports had increased adjusted odds of ciTBIs. CONCLUSIONS: Children with sports-related head trauma commonly undergo CT. Only 4% of those imaged had TBIs on CT. Clinically important TBIs occurred in 1%, with significant variation by sport. There is an opportunity for injury prevention efforts in high-risk sports and opportunities to reduce CT use in general by use of evidence-based prediction rules. What is known about this subject: Pediatric sports-related head injuries are a common and increasingly frequent ED presentation, as is the use of CT in their evaluation. Little is known about TBIs resulting from different types of sports activities in children. What this study adds to existing knowledge: This study broadens the understanding of the epidemiology of Pediatric TBIs resulting from different sports activities through a prospective assessment of frequency and severity of ciTBIs and ED CT use in a large cohort of head-injured children in a network of pediatric EDs. PMID- 26256637 TI - Telomere length predicts progression and overall survival in chronic lymphocytic leukemia: data from the UK LRF CLL4 trial. PMID- 26256638 TI - Efficient synthesis of novel antiproliferative steroidal spirooxindoles via the [3+2] cycloaddition reactions of azomethine ylides. AB - A series of novel steroidal spirooxindoles 3a-h were synthesized from pregnenolone in a high regioselective manner using the 1,3-dipolar cycloaddition as the key step. This protocol resulted in the formation of two C-C bonds, one C N bond and the creation of one pyrrolidine ring and three contiguous stereocenters in a single operation. Biological evaluation showed that these synthesized steroidal spirooxindoles exhibited moderate to good antiproliferative activity against the tested cell lines and some of them were more potent than 5 FU. Among them, compounds 3e and 3f displayed the best antiproliferative activity against MCF-7 cells with the IC50 values of 4.0 and 3.9MUM, respectively. Flow cytometry analysis demonstrated that compound 3d caused the cellular apoptosis and cell cycle arrest at G2/M phase in a concentration-dependent manner. Docking results indicated that compound 3d fitted well into the MDM2 active site 1RV1 by interacting with Lys94 and Thr101 residues. PMID- 26256639 TI - Chemical Vapor Deposition Synthesized Atomically Thin Molybdenum Disulfide with Optoelectronic-Grade Crystalline Quality. AB - The ability to synthesize high-quality samples over large areas and at low cost is one of the biggest challenges during the developmental stage of any novel material. While chemical vapor deposition (CVD) methods provide a promising low cost route for CMOS compatible, large-scale growth of materials, it often falls short of the high-quality demands in nanoelectronics and optoelectronics. We present large-scale CVD synthesis of single- and few-layered MoS2 using direct vapor-phase sulfurization of MoO2, which enables us to obtain extremely high quality single-crystal monolayer MoS2 samples with field-effect mobility exceeding 30 cm(2)/(V s) in monolayers. These samples can be readily synthesized on a variety of substrates, and demonstrate a high-degree of optoelectronic uniformity in Raman and photoluminescence mapping over entire crystals with areas exceeding hundreds of square micrometers. Because of their high crystalline quality, Raman spectroscopy on these samples reveal a range of multiphonon processes through peaks with equal or better clarity compared to past reports on mechanically exfoliated samples. This enables us to investigate the layer thickness and substrate dependence of the extremely weak phonon processes at 285 and 487 cm(-1) in 2D-MoS2. The ultrahigh, optoelectronic-grade crystalline quality of these samples could be further established through photocurrent spectroscopy, which clearly reveal excitonic states at room temperature, a feat that has been previously demonstrated only on samples which were fabricated by micro-mechanical exfoliation and then artificially suspended across trenches. Our method reflects a big step in the development of atomically thin, 2D-MoS2 for scalable, high-quality optoelectronics. PMID- 26256640 TI - Comparison between optical-resolution photoacoustic microscopy and confocal laser scanning microscopy for turbid sample imaging. AB - Optical-resolution photoacoustic microscopy (ORPAM) in theory provides lateral resolution equivalent to the optical diffraction limit. Scattering media, such as biological turbid media, attenuates the optical signal and also alters the diffraction-limited spot size of the focused beam. The ORPAM signal is generated only from a small voxel in scattering media with dimensions equivalent to the laser spot size after passing through scattering layers and is detected by an acoustic transducer, which is not affected by optical scattering. Thus, both ORPAM and confocal laser scanning microscopy (CLSM) reject scattered light. A multimodal optical microscopy platform that includes ORPAM and CLSM was constructed, and the lateral resolution of both modes was measured using patterned thin metal film with and without a scattering barrier. The effect of scattering media on the lateral resolution was studied using different scattering coefficients and was compared to computational results based on Monte Carlo simulations. It was found that degradation of lateral resolution due to optical scattering was not significant for either ORPAM or CLSM. The depth discrimination capability of ORPAM and CLSM was measured using microfiber embedded in a light scattering phantom material. ORPAM images demonstrated higher contrast compared to CLSM images partly due to reduced acoustic signal scattering. PMID- 26256641 TI - Phylogeny of Neotropical Cercosaura (Squamata: Gymnophthalmidae) lizards. AB - Among Neotropical lizards, the geographically widespread gymnophthalmid Cercosaura as currently defined includes lowland and highland taxa from Panama to Argentina, with some species occurring in the northern Andes. In this study we analyze three mitochondrial (12S, 16S, ND4) and one nuclear (c-mos) gene using Bayesian methods to clarify the phylogenetic relationships among most species of Cercosaura based on a well-supported phylogenetic hypothesis that also includes a large sample of other taxa within Cercosaurini. The phylogenetic tree obtained in this paper shows that Cercosaura as currently defined is not monophyletic. Two species from the northern Andes (C. dicra and C. vertebralis) are nested within Pholidobolus, which has been formerly recognized as a major radiation along the Andes of Ecuador and Colombia. Therefore, Cercosaura has probably not diversified in the northern Andes, although the phylogenetic position of C. hypnoides from the Andes of Colombia remains unknown. Tree topology and genetic distances support both recognition of C. ocellata bassleri as a distinct species, C. bassleri, and recognition of C. argula and C. oshaughnessyi as two different species. In the interest of promoting clarity and precision regarding the names of clades of gymnophthalmid lizards, we propose a phylogenetic definition of Cercosaura. PMID- 26256642 TI - Molecular phylogeny reveals the polyphyly of the snail genus Cepaea (Gastropoda: Helicidae). AB - Snails in the genus Cepaea are important model organisms in ecogenetic studies because of their colour and banding polymorphism. The monophyly of this group has been almost unanimously assumed based on superficial similarities in shell form and colouration. However, molecular phylogenetic analyses based on mitochondrial and nuclear sequences of 20 genera of Helicidae unequivocally demonstrated that Cepaea as currently understood is a polyphyletic assemblage. Only C. nemoralis and C. hortensis are retained in Cepaea, whereas C. vindobonensis is referred to Caucasotachea and C. sylvatica to Macularia based on our molecular phylogeny. Cepaea and Macularia belong to the western clade of the Helicinae, whereas Caucasotachea is nested in the eastern clade which probably diverged in the late Eocene. Because of the large phylogenetic distances between Cepaea, Macularia and Caucasotachea, it has to be shown whether the genetic mechanism underlying the simpler banding polymorphism in C. vindobonensis and M. sylvatica is a simpler version of the supergene that determines the polymorphism in Cepaea in the strict sense. This case illustrates the importance of sound phylogenetic analyses as a basis for any predictions in comparative biology. PMID- 26256643 TI - Twisted trees and inconsistency of tree estimation when gaps are treated as missing data - The impact of model mis-specification in distance corrections. AB - Statistically consistent estimation of phylogenetic trees or gene trees is possible if pairwise sequence dissimilarities can be converted to a set of distances that are proportional to the true evolutionary distances. Susko et al. (2004) reported some strikingly broad results about the forms of inconsistency in tree estimation that can arise if corrected distances are not proportional to the true distances. They showed that if the corrected distance is a concave function of the true distance, then inconsistency due to long branch attraction will occur. If these functions are convex, then two "long branch repulsion" trees will be preferred over the true tree - though these two incorrect trees are expected to be tied as the preferred true. Here we extend their results, and demonstrate the existence of a tree shape (which we refer to as a "twisted Farris-zone" tree) for which a single incorrect tree topology will be guaranteed to be preferred if the corrected distance function is convex. We also report that the standard practice of treating gaps in sequence alignments as missing data is sufficient to produce non-linear corrected distance functions if the substitution process is not independent of the insertion/deletion process. Taken together, these results imply inconsistent tree inference under mild conditions. For example, if some positions in a sequence are constrained to be free of substitutions and insertion/deletion events while the remaining sites evolve with independent substitutions and insertion/deletion events, then the distances obtained by treating gaps as missing data can support an incorrect tree topology even given an unlimited amount of data. PMID- 26256644 TI - Origin and intra-island diversification of Sulawesi endemic Adrianichthyidae. AB - Although the family Adrianichthyidae is broadly distributed throughout East and Southeast Asia, 19 endemic species, over half of the family, are distributed in Sulawesi, which is an island in Wallacea. However, it remains unclear how this Adrianichthyidae biodiversity hotspot was shaped. In this study, we reconstructed molecular phylogenies for the Sulawesi adrianichthyids and estimated the divergence times of major lineages to infer the detailed history of their origin and subsequent intra-island diversification. The mitochondrial and nuclear phylogenies revealed that Sulawesi adrianichthyids are monophyletic, which indicates that they diverged from a single common ancestor. Species in the earliest branching lineages are currently distributed in the central and southeastern parts of the island, indicating that the common ancestor colonized Sula Spur, which is a large promontory that projects from the Australian continental margin, from Asia by oversea dispersal c.a. 20Mya. The first diversification event on Sulawesi, the split of the genus Adrianichthys, occurred c.a. 16Mya, and resulted in the nesting of Adrianichthys within Oryzias. Strong geographic structure was evident in the phylogeny; many species in the lineages branching off early are riverine and widely distributed in the southeastern and southwestern arms of Sulawesi, which suggests that oversea dispersal between tectonic subdivisions of this island during the late Miocene (7-5Mya) contributed to the distributions and diversification of the early branching lineages. In contrast, most species in the lineages branched off later are endemic to a single tectonic lake or lake system in the central Sulawesi, suggesting that habitat fragmentation due to the Pliocene collisions (c.a. 4Mya) among the tectonic subdivisions was the primary factor for diversification of the late branching, lacustrine lineages. Adrianichthys and some Oryzias in a certain late branching lineage are sympatric in Lake Poso, which indicates multiple colonizations of these distinct lineages into this tectonic lake. Thus, the diversification of Sulawesi adrianichthyids largely reflects the complex geological history of this island. PMID- 26256645 TI - Expanding the horizons of G protein-coupled receptor structure-based ligand discovery and optimization using homology models. AB - With >800 members in humans, the G protein-coupled receptor (GPCR) super-family is the target for more than 30% of the marketed drugs. The recent boom in GPCR crystallography has enabled the solution of ~30 different GPCR structures, which boosted the identification and optimization of novel modulators and new chemical entities through structure-based strategies. However, the number of available structures represents a small part of the human GPCR druggable target space, and its complete coverage in the near future seems unlikely. Homology modelling represents a reliable tool to fill this gap, and hence to vastly expand the horizons of structure-based drug discovery and design. In this Feature Article, we show from a wealth of retrospective and prospective studies that in spite of the pitfalls of and standing challenges in homology modelling, structural models have been critical for the blossoming and success of GPCR structure-based lead discovery and optimization endeavours; in addition, they have also been instrumental in characterizing receptor-ligand interaction, guiding the design of site-directed mutagenesis and SAR studies, and assessing off-target effects. Considering though their current limitations, we also discuss the most pressing issues to develop more accurate homology modelling strategies, with a special focus on the integration of computational tools with biochemical, biophysical and QSAR data, highlighting methodological aspects and recent progress. The teachings of the three GPCR Dock community-wide assessments and the fresh developments in GPCR classes B, C and F are commented. This is a fast growing and highly promising field of research, and in the coming years, the use of high-quality models should enable the discovery of a growing number of potent, selective and efficient GPCR drug leads with high therapeutic potential through receptor structure-based strategies. PMID- 26256646 TI - Tumor Suppressor WWOX inhibits osteosarcoma metastasis by modulating RUNX2 function. AB - Osteosarcoma (OS) is among the most frequently occurring primary bone tumors, primarily affecting adolescents and young adults. This malignant osteoid forming tumor is characterized by its metastatic potential, mainly to lungs. We recently demonstrated that WW domain-containing oxidoreductase (WWOX) is frequently inactivated in human OS and that WWOX restoration in WWOX-negative OS cells suppresses tumorigenicity. Of note, WWOX levels are reduced in paired OS samples of post-treatment metastastectomies as compared to pre-treatment biopsies suggesting that decreased WWOX levels are associated with a more aggressive phenotype at the metastatic site. Nevertheless, little is known about WWOX function in OS metastasis. Here, we investigated the role of tumor suppressor WWOX in suppressing pulmonary OS metastasis both in vitro and in vivo. We demonstrated that ectopic expression of WWOX in OS cells, HOS and LM-7, inhibits OS invasion and cell migration in vitro. Furthermore, WWOX expression reduced tumor burden in vivo and inhibited metastases' seeding and colonization. Mechanistically, WWOX function is associated with reduced levels of RUNX2 metastatic target genes implicated in adhesion and motility. Our results suggest that WWOX plays a critical role in determining the aggressive phenotype of OS, and its expression could be an attractive therapeutic target to combat this devastating adolescent disease. PMID- 26256647 TI - Comparative study of the radiobiological effects induced on adherent vs suspended cells by BNCT, neutrons and gamma rays treatments. AB - The present work is part of a preclinical in vitro study to assess the efficacy of BNCT applied to liver or lung coloncarcinoma metastases and to limb osteosarcoma. Adherent growing cell lines can be irradiated as adherent to the culture flasks or as cell suspensions, differences in radio-sensitivity of the two modalities of radiation exposure have been investigated. Dose related cell survival and cell cycle perturbation results evidenced that the radiosensitivity of adherent cells is higher than that of the suspended ones. PMID- 26256648 TI - An effective homogenate-assisted negative pressure cavitation extraction for the determination of phenolic compounds in pyrola by LC-MS/MS and the evaluation of its antioxidant activity. AB - A novel extraction method, homogenate-assisted negative pressure cavitation extraction (HNPCE), was designed for the extraction and determination of the main phenolic compounds of Pyrola incarnata Fisch. by LC-MS/MS. The particle sizes and extraction yields in the process of homogenization were compared with conventional pulverization. The results showed that homogenization for less than 120 s could produce more suitable particle size powders for analyte extraction. The following NPCE parameters were optimized by a BBD test and under the optimal conditions, the maximum extraction yields of arbutin, epicatechin, hyperin, 2'-O galloylhyperin and chimaphilin increased by 68.7%, 72.0%, 43.3%, 62.5% and 34.5% with respect to normal NPCE. The LC-MS/MS method was successfully applied for the quantification of five target compounds in pyrola, and the results of the precision test indicated a high accuracy of the present method for the quantification of the target compounds in pyrola. Furthermore, the antioxidant activities of the pyrola extracts were also determined. The results showed that pyrola had good antioxidant activities and it was a valuable antioxidant natural source. PMID- 26256649 TI - Pregnancy outcomes in women with growth hormone deficiency. AB - OBJECTIVE: To study pregnancies in a large group of patients with growth hormone deficiency and hypopituitarism; and to investigate potential factors determining pregnancy outcomes and pregnancy complications. DESIGN: We analyzed pregnancies reported in KIMS, the Pfizer International Metabolic Database, of adult patients with growth hormone deficiency treated with growth hormone. SETTING: Outpatient clinics. PATIENT(S): A total of 201 pregnancies were reported: 173 in female patients and 28 in partners of male patients. INTERVENTION(S): Growth hormone replacement therapy (GHRT) was prescribed according to the local clinical practice. MAIN OUTCOME MEASURE(S): Pregnancy outcomes (live births, gestational week at delivery, and birth weight), pregnancy complications, and their relationship to use of GHRT during pregnancy were analyzed with regression models. RESULT(S): Two-thirds of women underwent fertility treatment to achieve pregnancy. Growth hormone replacement therapy was stopped before pregnancy in 7.5% of the female patients, as soon as pregnancy was confirmed in 40.1%, and at the end of the second trimester in 24.7% of the patients, whereas 27.6% continued GHRT throughout pregnancy. Birth of a healthy child was reported in 79% of the female pregnancies, nonelective abortions occurred mainly in the first trimester, and one fetal malformation (cystic hygroma) was diagnosed in the second trimester. Pregnancy outcomes and pregnancy complications were not related to GHRT treatment patterns, method of conception, or number of additional pituitary deficiencies. CONCLUSION(S): These data on pregnancy outcomes in a large group of women with hypopituitarism revealed no relationship between GHRT regimens and pregnancy outcomes. PMID- 26256650 TI - Sterile reprocessing of surgical instruments in low- and middle-income countries: A multicenter pilot study. AB - BACKGROUND: Surgical site infections increase the morbidity, mortality, and costs associated with surgical care. An estimated 96.2 million surgical procedures are performed in low- and middle-income countries (LMICs) each year. This pilot study assessed the steam sterilization aspect of the surgical instrument reprocessing practice in LMIC hospitals. METHODS: Surgeons representing 26 hospitals in 9 different LMICs were consented to test the single most frequently used autoclave in their respective surgical departments. Participants conducted 10 chemical integrator tests and recorded the total cycle time, exposure temperature, and pressure on each test. Data were analyzed with descriptive statistics and reviewed by medical reprocessing experts. RESULTS: Nine of the 26 (35%) study sites representing 7 countries returned their autoclave data and test strips (n = 90). Of the sites, 78% obtained acceptable readings on all 10 tests. When the data were compared against the recommended parameters for sterility, the results were less favorable. All 90 tests had at least 1 variable not within the target exposure time, temperature, or pressure. CONCLUSION: This pilot study presents concerns in regard to the effectiveness of steam autoclaves used in LMIC hospitals and the subsequent risks this presents to surgical patients. We acknowledge the resource limitations in many LMIC hospitals. However, the international medical community must ensure that basic sterile practice guidelines are adhered to despite these constraints. PMID- 26256651 TI - Forearm articular proportions and the antebrachial index in Homo sapiens, Australopithecus afarensis and the great apes. AB - When hominin bipedality evolved, the forearms were free to adopt nonlocomotor tasks which may have resulted in changes to the articular surfaces of the ulna and the relative lengths of the forearm bones. Similarly, sex differences in forearm proportions may be more likely to emerge in bipeds than in the great apes given the locomotor constraints in Gorilla, Pan and Pongo. To test these assumptions, ulnar articular proportions and the antebrachial index (radius length/ulna length) in Homo sapiens (n=51), Gorilla gorilla (n=88), Pan troglodytes (n=49), Pongo pygmaeus (n=36) and Australopithecus afarensis A.L. 288 1 and A.L. 438-1 are compared. Intercept-adjusted ratios are used to control for size and minimize the effects of allometry. Canonical scores axes show that the proximally broad and elongated trochlear notch with respect to size in H. sapiens and A. afarensis is largely distinct from G. gorilla, P. troglodytes and P. pygmaeus. A cluster analysis of scaled ulnar articular dimensions groups H. sapiens males with A.L. 438-1 ulna length estimates, while one A.L. 288-1 ulna length estimate groups with Pan and another clusters most closely with H. sapiens, G. gorilla and A.L. 438-1. The relatively low antebrachial index characterizing H. sapiens and non-outlier estimates of A.L. 288-1 and A.L. 438-1 differs from those of the great apes. Unique sex differences in H. sapiens suggest a link between bipedality and forearm functional morphology. PMID- 26256652 TI - [Venous compression in venous insufficiency]. AB - Compression is a mandatory therapeutic measure in all stages of venous insufficiency. This treatment, recommended by the French Health Authority (HAS), is consistently included in the protocols of therapeutic studies involving venous ulcers. Given the great variety in materials available and in the approaches of individual doctors, it is essential to avoid a dogmatic approach and instead to adapt treatment to the therapeutic results based on the premise that well controlled treatment should result in improvement in trophic disorders and in patient comfort, while poor treatment is badly tolerated, even potentially harmful, and rejected by patients. Manufacturers have made great progress in the design of compression hose and bandages; however, to assess this treatment using the evidence-based medical methods stipulated by learned societies, great rigour is demanded in clinical trials, and the active substances, mode of action and requisite "dosages" must be precisely defined. PMID- 26256653 TI - [Recognising and treating lipidema OMIM 614103]. AB - Lipedema is a poorly understood clinical entity that is frequently under diagnosed and neglected or else confused with lymphoedema. However, in most cases, diagnosis is simple and does not usually necessitate laboratory examinations. There is an extremely high demand for therapy since the condition causes major morbidity and affects quality of life. The aim of treatment is to reduce patient weight; although weight loss does not affect the morphology of the lower limbs, it optimises patient mobility while reducing related complaints and improving quality of life. Conservative surgical measures, of which tumescent liposuction is the most frequent, provide improvement of certain symptoms. A better understanding of this entity will result in improved therapy. PMID- 26256654 TI - An efficient thermal evolution model for cryoablation with arbitrary multi cryoprobe configuration. AB - Cryoablation has been demonstrated powerful in treating of a variety of diseases, especially for the tumor ablation, which destroys the target tissue through the controlled freezing of cryoprobe. The prediction of temperature evolution during cryoablation is of great importance for developing and improving clinical procedure. This paper presented an efficient thermal model to characterize the freezing effect of cryoprobe with arbitrary layout including its size, orientation and number. The key step of the presented model is to establish a boundary heat source method to implicitly characterize the heat transfer from cryoprobe with fixed temperature or convective heat transfer boundary condition, which is furthermore incorporated to a fast parallel alternating direction explicit (PADE) finite difference method for computation acceleration. A novel dynamical and conformal computational region is designed through the shortest distance definition to balance the thermal effect of tissue and computational efficiency. The detailed test cases including a real head tissue demonstrated that the current model can accurately predict the temperature field evolution induced by arbitrary multi-cryoprobe configuration, and achieve significant computational ability due to allowable large time step (100-fold compared with the explicit finite difference method), compact computational region (at least reducing 40% number of voxels) and high parallel efficiency (speedup ratio about 8 for 12 threads) for complex tissue structure. PMID- 26256655 TI - Derivatisation for separation and detection in capillary electrophoresis (2012 2015). AB - Derivatisation is a well-established and mature form of sample preparation for CE. The modification of the analyte can cause superior analysis characteristics such as better sensitivity and selectivity, however, derivatisation of the analyte introduces an additional step into the analytical workflow. This review covers articles from January 2012 to January 2015 on derivatisation in CE. The main sections are on the derivatisation modes (i.e. pre-capillary, in-line, in capillary and post-capillary), separation and detection modes (i.e. LIF and others). LIF is discussed in more detail since this detection mode was most prevalent. A table of the common labelling agents and wavelengths for excitation and emission and the common derivatisation reactions are included. In addition, a comprehensive table which summarises all research articles is provided. This review is suitable for analytical chemists as a guide for 'how to get started' with derivatisation for separation and detection in CE. PMID- 26256656 TI - Maturing out, natural recovery, and dual diagnosis: What are the implications for older adult mental health services? AB - In 1962, Charles Winick proposed that addiction was a self-limiting process, whereby individuals stopped using substances once the stresses of life transitions ceased. The notion of maturing out, as labelled by Winick, often forms the basis of the natural recovery movement in alcohol and other drug (AOD) research, aiding the notion that older individuals either cease their substance use or fall victim to the higher mortality rates prevalent in substance-using populations. As more consumers present to adult mental health treatment settings with co-occurring substance use disorders, the idea that individuals will simply cease using AOD is outdated. Given the future challenges of an ageing population, it is prudent to explore those who fail to mature out of substance use, as well as challenge the notion that older adult mental health services rarely encounter substance-using individuals. The present study explores Winick's research in the context of an ageing population and older adult mental health services. It also ponders the proposition put forth in subsequent research that older individuals with lifelong substance use switch to substances that are easier to obtain and better tolerated by their ageing bodies. PMID- 26256657 TI - Portal vein anatomy in the dog: comparison between computed tomographic angiography (CTA) and intraoperative mesenteric portovenography (IOMP). AB - OBJECTIVES: To compare and contrast the findings of intra-operative mesenteric portovenography (IOMP) and computed tomography angiography (CTA) for the visualisation and identification of the extrahepatic and intrahepatic portal venous system in the normal dog. METHODS: Retrospective study of dogs with raised post-prandial bile acids concentrations, normal portal venous pressures and grossly normal portal vasculature that had undergone both CTA and IOMP was performed. Images and video were compared with the published anatomic literature. RESULTS: Ten dogs met the inclusion criteria. CTA documented the portal vein and its tributaries in all 10 dogs. IOMP documented the portal vein and the cranial mesenteric vein in all 10 dogs and the splenic vein in 1 dog but failed to show the caudal mesenteric and gastroduodenal veins in any dog. CTA documented more extrahepatic portal venous tributaries than IOMP. Both techniques documented the intrahepatic portal vasculature completely with equal clarity. CLINICAL SIGNIFICANCE: There was a large difference between the ability of the two techniques to delineate the normal portal vasculature; CTA consistently visualised the extrahepatic portal vasculature more completely than the IOMP and, as such, might be considered the modality of choice for imaging the normal portal vasculature in the dog. PMID- 26256658 TI - Prognostic Tools for Early Mortality in Hemorrhagic Stroke: Systematic Review and Meta-Analysis. AB - BACKGROUND AND PURPOSE: Several risk scores have been developed to predict mortality in intracerebral hemorrhage (ICH). We aimed to systematically determine the performance of published prognostic tools. METHODS: We searched MEDLINE and EMBASE for prognostic models (published between 2004 and April 2014) used in predicting early mortality (<6 months) after ICH. We evaluated the discrimination performance of the tools through a random-effects meta-analysis of the area under the receiver operating characteristic curve (AUC) or c-statistic. We evaluated the following components of the study validity: study design, collection of prognostic variables, treatment pathways, and missing data. RESULTS: We identified 11 articles (involving 41,555 patients) reporting on the accuracy of 12 different tools for predicting mortality in ICH. Most studies were either retrospective or post-hoc analyses of prospectively collected data; all but one produced validation data. The Hemphill-ICH score had the largest number of validation cohorts (9 studies involving 3,819 patients) within our systematic review and showed good performance in 4 countries, with a pooled AUC of 0.80 [95% confidence interval (CI)=0.77-0.85]. We identified several modified versions of the Hemphill-ICH score, with the ICH-Grading Scale (GS) score appearing to be the most promising variant, with a pooled AUC across four studies of 0.87 (95% CI=0.84-0.90). Subgroup testing found statistically significant differences between the AUCs obtained in studies involving Hemphill-ICH and ICH-GS scores (p=0.01). CONCLUSIONS: Our meta-analysis evaluated the performance of 12 ICH prognostic tools and found greater supporting evidence for 2 models (Hemphill-ICH and ICH-GS), with generally good performance overall. PMID- 26256659 TI - Whole-Body Muscle MRI in Patients with Hyperkalemic Periodic Paralysis Carrying the SCN4A Mutation T704M: Evidence for Chronic Progressive Myopathy with Selective Muscle Involvement. AB - BACKGROUND AND PURPOSE: Hyperkalemic periodic paralysis (hyperKPP) is a muscle sodium-ion channelopathy characterized by recurrent paralytic attacks. A proportion of affected individuals develop fixed or chronic progressive weakness that results in significant disability. However, little is known about the pathology of hyperKPP-induced fixed weakness, including the pattern of muscle involvement. The aim of this study was to characterize the patterns of muscle involvement in hyperKPP by whole-body magnetic resonance imaging (MRI). METHODS: We performed whole-body muscle MRI in seven hyperKPP patients carrying the T704M mutation in the SCN4A skeletal sodium-channel gene. Muscle fat infiltration, suggestive of chronic progressive myopathy, was analyzed qualitatively using a grading system and was quantified by the two-point Dixon technique. RESULTS: Whole-body muscle MRI analysis revealed muscle atrophy and fatty infiltration in hyperKPP patients, especially in older individuals. Muscle involvement followed a selective pattern, primarily affecting the posterior compartment of the lower leg and anterior thigh muscles. The muscle fat fraction increased with patient age in the anterior thigh (r=0.669, p=0.009), in the deep posterior compartment of the lower leg (r=0.617, p=0.019), and in the superficial posterior compartment of the lower leg (r=0.777, p=0.001). CONCLUSIONS: Our whole-body muscle MRI findings provide evidence for chronic progressive myopathy in hyperKPP patients. The reported data suggest that a selective pattern of muscle involvement-affecting the posterior compartment of the lower leg and the anterior thigh-is characteristic of chronic progressive myopathy in hyperKPP. PMID- 26256660 TI - Dysphagia May Be an Independent Marker of Poor Outcome in Acute Lateral Medullary Infarction. AB - BACKGROUND AND PURPOSE: The functional recovery after the lateral medullary infarction (LMI) is usually good. Little is known about the prognostic factors associated with poor outcome following acute LMI. The aim of this study was to identify the factors associated with poor long-term outcome after acute LMI, based on experiences at a single center over 11 years. METHODS: A consecutive series of 157 patients with acute LMI who were admitted within 7 days after symptom onset was evaluated retrospectively. Clinical symptoms were assessed within 1 day after admission, and outcomes were evaluated over a 1-year period after the initial event. The lesions were classified into three vertical types (rostral, middle, and caudal), and the patients were divided into two groups according to the outcome at 1 year: favorable [modified Rankin Scale (mRS) score <=1] and unfavorable (mRS score >=2). RESULTS: Of the 157 patients, 93 (59.2%) had a favorable outcome. Older age, hypertension, dysphagia, requirement for intensive care, and pneumonia were significantly more prevalent in the unfavorable outcome group. The frequencies of intensive care (13%) and mortality (16.7%) were significantly higher in the rostral lesion (p=0.002 and p=0.002). Conditional logistic regression analysis revealed that older age and initial dysphagia were independently related to an unfavorable outcome at 1 year [odds ratio (OR)=1.04, 95% confidence interval (95% CI)=1.001-1.087, p=0.049; OR=2.46, 95% CI=1.04-5.84, p=0.041]. CONCLUSIONS: These results suggest that older age and initial dysphagia in the acute phase are independent risk factors for poor long term prognosis after acute LMI. PMID- 26256661 TI - Bilateral Iatrogenic Femoral Neuropathy. PMID- 26256662 TI - Multiple Symmetric Lipomatosis Presenting with Bilateral Brachial Plexopathy. PMID- 26256663 TI - Clinical Characteristics of Primary Insomniacs with Sleep-State Misperception. AB - BACKGROUND AND PURPOSE: The aims of this study were to determine the prevalence of sleep-state misperception and to identify any differences in the clinical characteristics of primary insomniacs with and without misperception. METHODS: In total, 250 adult primary insomniacs were enrolled whose objective total sleep time (TST) was more than 120 min, as assessed by full-night polysomnography. Sleep state misperception was defined objectively as a TST of at least 6.5 h and an objective sleep efficiency (SE) of at least 85%. RESULTS: The prevalence of sleep-state misperception in primary insomniacs was 26.4%. The (low) quality of sleep and psychiatric parameters were similar in the two groups, although the objective sleep architecture was relatively normal for the misperception group. Multivariate analysis revealed that both SE and sleep quality were significant factors associated with subjective TST in the misperception group, while only SE was significant in those without misperception. Subjective TST was a significant effect factor with respect to sleep quality in the misperception group, while the Beck Depression Inventory-2 score and age were significant factors in those without misperception. CONCLUSIONS: The clinical characteristics of patients with sleep-state misperception differed from those without this condition. This suggests that these two groups should be separated and the treatment goals tailored specifically to each. PMID- 26256664 TI - Rhinology and medical malpractice: An update of the medicolegal landscape of the last ten years. AB - OBJECTIVES/HYPOTHESIS: Malpractice claims pertaining to rhinological procedures are a potentially important source of information that could be used to minimize the risk of future litigation and improve patient care. STUDY DESIGN: A retrospective review of a publicly available database containing jury verdicts and settlements. METHODS: The LexisNexis Jury Verdicts and Settlements database was reviewed for all lawsuits and out-of-court adjudications related to the practice of rhinology. Data including patient demographics, type of surgery performed, plaintiff allegation, nature of injury, outcomes, and indemnities were collected and analyzed. RESULTS: Of 85 cases meeting inclusion criteria, 42 were decided by a jury and 43 were adjudicated out of court. Endoscopic sinus surgery was the most commonly litigated surgery. The plaintiff was favored when the eye was injured (P = 0.0196), but the defendant was favored when neuropsychological injuries (P = 0.0137) or recurrent/worsened symptoms (P = 0.0050) were cited. No difference was found when death or skull base injuries occurred. When lack of informed consent was an allegation, the defendant was favored (P = 0.0001). A payout was made in two-thirds of cases overall, but the defendant was favored in two-thirds of cases decided by a jury. Payments were significant for both out-of court settlements ($1.3 million) and jury verdicts ($2 million). CONCLUSIONS: Endoscopic sinus surgery remains the most commonly litigated rhinology procedure and has the potential to result in large payouts. Meticulous dissection, recognition of complications, and documentation of informed consent remain paramount for providing optimal patient care. PMID- 26256665 TI - Improvement of Fish Sauce Quality by Strain CMC5-3-1: A Novel Species of Staphylococcus sp. AB - Staphylococcus sp. CMC5-3-1 and CMS5-7-5 isolated from fermented fish sauce at 3 to 7 mo, respectively, showed different characteristics on protein hydrolysis and volatile formation. These Gram-positive cocci were able to grow in up to 15% NaCl with the optimum at 0.5% to 5% NaCl in tryptic soy broth. Based on ribosomal 16S rRNA gene sequences, Staphylococcus sp. CMC5-3-1 and CMS5-7-5 showed 99.0% similarity to that of Staphylococcus piscifermentans JCM 6057(T) , but DNA-DNA relatedness was <30%, indicating that they were likely to be new species. DNA relatedness between these 2 strains was only 65%, suggesting that they also belonged to different species. The alpha-amino group content of 6-month-old fish sauce inoculated with Staphylococcus sp. CMC5-3-1 was 740.5 mM, which was higher than that inoculated by the strain CMS5-7-5 (662.14 mM, P < 0.05). Histamine was not produced during fermentations with both strains. Fish sauce inoculated with Staphylococcus sp. CMC5-3-1 showed the highest content of total glutamic acid (P < 0.05). The major volatile compound detected in fish sauce inoculated with Staphylococcus sp. CMC5-3-1 was 2-methypropanal, contributing to the desirable dark chocolate note. Staphylococcus sp. CMC5-3-1 could be applied as a starter culture to improve the umami and aroma of fish sauce. PMID- 26256666 TI - Ornithine Transcarbamylase ArgK Plays a Dual role for the Self-defense of Phaseolotoxin Producing Pseudomonas syringae pv. phaseolicola. AB - Pseudomonas syringae is a phytopathogenic bacterium widely spread on terrestrial plants. Sulfodiaminophosphinyl tripeptide Phaseolotoxins (PHTs), produced by P. syringae pv. phaseolicola and P. syringae pv. actinidiae, represent a kind of antimetabolic phytotoxins. PHTs inhibit host cell Ornithine transcarbamylase (OTCase) activity and induce Arginine auxotrophic phenotype. The biosynthesis of PHT is temperature dependent, being optically produced at around 18 degrees C, while blocked above 28 degrees C. PHT resistant OTCase ArgK acts as a functional replacement of housekeeping OTCase ArgF, which is the acting target of PHT, to confer PHT producers with self-resistance. It was postulated that argK might be regulated directly by a PHT biosynthetic precursor and indirectly by temperature with an unknown manner. Neither transcriptional regulator nor thermal regulation related protein encoding gene was detected from PHT biosynthetic gene cluster. The tripeptide, Cit-Ala-hArg, was identified to be a by-product of PHT biosynthetic pathway in this report. Formation of Cit-Ala-hArg was catalyzed by ArgK with tripeptide Orn-Ala-hArg and carbamyl phosphate as substrates. It showed that ArgK not only provided alternative Arginine source as reported previously, but also controlled the production of PHTs by converting PHT biosynthetic precursors to nontoxic Cit-Ala-hArg reservoir for producers' self-defense. PMID- 26256667 TI - Predictors of Long-Term Survival Following Transvenous Extraction of Defibrillator Leads. AB - BACKGROUND: Little data exist on long-term outcomes following extraction of implantable cardioverter defibrillator (ICD) leads, particularly for noninfectious indications. We sought to identify predictors of long-term survival after ICD lead extraction. METHODS: We retrospectively reviewed ICD lead extractions at our institution (n = 508). Procedural outcomes and long-term survival were ascertained by medical records review. RESULTS: Indication for lead extraction was infection in 32.5% and lead failure in 61.8%. Mean dwell time of the oldest extracted lead was 5.1 +/- 5.9 years. Complete procedural success was achieved in 96.5% of cases. Major procedure-related complications occurred in 1.6% with six periprocedural deaths. During a mean follow-up of 866 +/- 798 days, survival was significantly worse among patients with infection as the indication for extraction. At 1 year after extraction, survival among those with infection was 88.2%, compared to 95.0% in the lead failure cohort (P < 0.001). Procedural failure was a significant predictor of long-term mortality, even after excluding periprocedural deaths. In multivariate models, the presence of chronic kidney disease, increased number of leads requiring extraction, lower ejection fraction, and procedural failure were predictors of mortality. CONCLUSION: Despite high rates of procedural success, infectious indication for ICD lead extraction is associated with increased long-term mortality. In contrast, among patients undergoing extraction for lead failure, long-term survival was excellent. The presence of procedural failure was a significant predictor of long-term mortality. Further studies will be necessary to better understand the mechanisms by which procedural failure may adversely impact long-term outcomes. PMID- 26256669 TI - Integrating nutrients, foods, diets, and appetites with obesity and cardiometabolic health. PMID- 26256668 TI - B-cell intrinsic TLR7 signals promote depletion of the marginal zone in a murine model of Wiskott-Aldrich syndrome. AB - Patients with Wiskott-Aldrich syndrome (WAS) exhibit prominent defects in splenic marginal zone (MZ), resulting in abnormal T-cell-independent antibody responses and increased bacterial infections. B-cell-intrinsic deletion of the affected gene WAS protein (WASp) markedly reduces splenic MZ B cells, without impacting the rate of MZ B-cell development, suggesting that abnormal B-cell retention within the MZ accounts for MZ defects in WAS. Since WASp regulates integrin dependent actin cytoskeletal rearrangement, we previously hypothesized that defective B-cell integrin function promotes MZ depletion. In contrast, we now report that B-cell-intrinsic deletion of the TLR signaling adaptor MyD88 is sufficient to restore the MZ in WAS. We further identify TLR7, an endosomal single-stranded RNA (ssRNA) receptor, as the MyD88-dependent receptor responsible for WAS MZ depletion. These findings implicate spontaneous activation of MZ B cells by ssRNA-containing self-ligands (likely derived from circulating apoptotic material) as the mechanism underlying MZ depletion in WAS. Together, these data suggest a previously unappreciated role for B-cell intrinsic TLR signals in MZ homeostasis, of relevance to both pathogen responses and to the development of systemic autoimmunity. PMID- 26256670 TI - Interactions Among Learning Stage, Retention, and Primary Motor Cortex Excitability in Motor Skill Learning. AB - BACKGROUND: Previous studies have shown that primary motor cortex (M1) excitability is modulated by motor skill learning and that the M1 plays a crucial role in motor memory. However, the following questions remain: (1) At what stage do changes in M1 excitability occur? (2) Are learning-induced changes in leg M1 excitability associated with motor memory? Here, we did two experiments to answer these questions. METHODS AND RESULTS: In experiment 1, subjects learned a visuomotor tracking task over two consecutive days. Before and after the task in Day 1, we recorded input-output curves of the motor evoked potentials (I-O curve) produced in the tibialis anterior muscle by transcranial magnetic stimulation. We found that the changes in M1 excitability were affected by learning stage. In addition, the changes in M1 excitability in Day 1 were correlated with the retention. In experiment 2, we recorded I-O curves before learning, after the fast-learning stage, and after learning. We found no changes in M1 excitability immediately after the fast-learning stage. Furthermore, a significant relationship between the length of slow-learning stage and the changes in M1 excitability was detected. CONCLUSIONS: Previous studies have suggested that optimal motor commands are repeatedly used during the slow-learning stage. Therefore, present results indicate that changes in M1 excitability occur during the slow-learning stage and that such changes are proportional to motor skill retention because use-dependent plasticity occur by repetitive use of same motor commands during the slow-learning stage. PMID- 26256671 TI - Optically controlled switch-mode current-source amplifiers for on-coil implementation in high-field parallel transmission. AB - PURPOSE: We tested the feasibility of implementing parallel transmission (pTX) for high-field MRI using a radiofrequency (RF) amplifier design to be located on or in the immediate vicinity of an RF transmit coil. METHOD: We designed a current-source switch-mode amplifier based on miniaturized, nonmagnetic electronics. Optical RF carrier and envelope signals to control the amplifier were derived, through a custom-built interface, from the RF source accessible in the scanner control. Amplifier performance was tested by benchtop measurements as well as with imaging at 7T (300 MHz) and 11.7 T (500 MHz). The ability to perform pTX was evaluated by measuring interchannel coupling and phase adjustment in a two-channel setup. RESULTS: The amplifier delivered in excess of 44 W RF power and caused minimal interference with MRI. The interface derived accurate optical control signals with carrier frequencies ranging from 64 to 750 MHz. Decoupling better than 14 dB was obtained between two coil loops separated by only 1 cm. Application to MRI was demonstrated by acquiring artifact-free images at 7 T and 11.7 T. CONCLUSION: We propose an optically controlled miniaturized RF amplifier for on-coil implementation at high fields that should facilitate implementation of high-density pTX arrays. Magn Reson Med 76:340-349, 2016. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. PMID- 26256673 TI - Parental perceptions of transition from intensive care following a child's cardiac surgery. AB - BACKGROUND: Children with congenital heart disease (CHD) who undergo cardiac surgery are hospitalized in a paediatric intensive care unit (PICU) prior to being transferred to a surgical ward. This is a challenging transition for parents of children with CHD who experience high levels of stress related to their child's illness. AIM: To explore parents' perceptions of the transition from the PICU to the surgical ward following their child's cardiac surgery. STUDY DESIGN: A qualitative descriptive design using semi-structured interviews was used to explore parents' perceptions of the transfer experience. METHODS: All parents of children with CHD who met inclusion criteria were approached to participate. Parents were recruited until data saturation was achieved (n = 9). Interviews were audiotaped and transcribed verbatim. Transcripts were coded and thematically analysed concurrently with data collection. RESULTS: Parents described having mixed feelings of happiness and uncertainty upon learning that their child would be transferred to the surgical ward (theme 1). Parents' uncertainty prompted a need to rally for the upcoming transfer, a process in which the nurse was perceived to play an important role (theme 2). Once transferred to the surgical ward, parents described having to come to terms with a new care experience in which they encountered new role expectations and a challenging new environment (theme 3). CONCLUSION: Emotional reactions to transfer were generally consistent with the literature, although parents in our study did not describe feelings of isolation related to transition as reported elsewhere. We also identified the timing of transfer as a potential source of stress for parents. Parents identified key nursing interventions that helped them to prepare for transfer and come to terms with challenges in their new environment. RELEVANCE TO PRACTICE: A deeper understanding of parents' transfer experience will facilitate the development of effective nursing interventions to support parents at this time. PMID- 26256672 TI - Molecular simulations study of novel 1,4-dihydropyridines derivatives with a high selectivity for Cav3.1 calcium channel. AB - 1,4-Dihydropyridines (DHPs) have been developed to treat hypertension, angina, and nerve system disease. They are thought to mainly target the L-type calcium channels, but low selectivity prompts them to block Cav1.2 and Cav3.1 channels simultaneously. Recently, some novel DHPs with different hydrophobic groups have been synthesized and among them M12 has a higher selectivity for Cav3.1. However, the structural information about Cav3.1-DHPs complexes is not available in the experiment. Thus, we combined homology modeling, molecular docking, molecular dynamics simulations, and binding free energy calculations to quantitatively elucidate the inhibition mechanism of DHPs. The calculated results indicate that our model is in excellent agreement with experimental results. On the basis of conformational analysis, we identify the main interactions between DHPs and calcium channels and further elaborate on the different selectivity of ligands from the micro perspective. In conjunction with energy distribution, we propose that the binding sites of Cav3.1-DHPs is characterized by several interspersed hydrophobic amino acid residues on the IIIS6 and IVS6 segments. We also speculate the favorable function groups on prospective DHPs. Besides, our model provides important information for further mutagenesis experiments. PMID- 26256674 TI - The impact of CYP3A5*3 polymorphism on sirolimus pharmacokinetics: insights from predictions with a physiologically-based pharmacokinetic model. AB - AIMS: Sirolimus is an mTOR inhibitor metabolized by CYP3A4 and CYP3A5. Reported effects of CYP3A5 polymorphisms on sirolimus pharmacokinetics (PK) have shown unexplained discrepancies across studies. We quantitatively assessed the effect of CYP3A5*3 status on sirolimus PK by in vitro assessment and simulation using a physiologically-based PK (PBPK) model. In addition, we explored designs for an adequately powered pharmacogenetic association study. METHOD: In vitro metabolism studies were conducted to confirm individual CYP contribution to sirolimus metabolism. PK profiles were simulated in CYP3A5 expressers and non-expressers with a PBPK model. The pre-dose concentration predictions were used as the outcome parameter to estimate the required sample size for a pharmacogenetic association study. RESULTS: Sirolimus metabolism was inhibited by over 90% by ketoconazole, a CYP3A specific inhibitor. The PBPK model developed based on CL(int) of recombinant CYP3A4, CYP3A5 and CYP2C8 predicted a small CYP3A5*3 effect on simulated sirolimus PK profiles. A subsequent power analysis based on these findings indicated that at least 80 subjects in an enrichment design, 40 CYP3A5 expressers and 40 non-expressers, would be required to detect a significant difference in the predicted trough concentrations at 1 month of therapy (P < 0.05, 80% power). CONCLUSIONS: This study suggests that CYP3A5 contribution to sirolimus metabolism is much smaller than that of CYP3A4. Observed discrepancies across studies could be explained as the result of inadequate sample size. PBPK model simulations allowed mechanism-based evaluation of the effects of CYP3A5 genotype on sirolimus PK and provided preliminary data for the design of a future prospective study. PMID- 26256675 TI - (1)H NMR spectra of alcohols in hydrogen bonding solvents: DFT/GIAO calculations of chemical shifts. AB - Proton nuclear magnetic resonance (NMR) shifts of aliphatic alcohols in hydrogen bonding solvents have been computed on the basis of density functional theory by applying the gauge-including atomic orbital method to geometry-optimized alcohol/solvent complexes. The OH proton shifts and hydrogen bond distances for methanol or ethanol complexed with pyridine depend very much on the functional employed and very little on the basis set, provided it is sufficiently large to give the correct quasi-linear hydrogen bond geometry. The CH proton shifts are insensitive to both the functional and the basis set. NMR shifts for all protons in several alcohol/pyridine complexes are calculated at the Perdew, Burke and Ernzerhof PBE0/cc-pVTZ//PBE0/6-311 + G(d,p) level in the gas phase. The results correlate with the shifts for the pyridine-complexed alcohols, determined by analysing data from the NMR titration of alcohols against pyridine. More pragmatically, computed shifts for a wider range of alcohols correlate with experimental shifts in neat pyridine. Shifts for alcohols in dimethylsulfoxide, based on the corresponding complexes in the gas phase, correlate well with the experimental values, but the overall root mean square difference is high (0.23 ppm), shifts for the OH, CHOH and other CH protons being systematically overestimated, by averages of 0.42, 0.21 and 0.06 ppm, respectively. If the computed shifts are corrected accordingly, a very good correlation is obtained with a gradient of 1.00 +/- 0.01, an intercept of 0.00 +/- 0.02 ppm and a root mean square difference of 0.09 ppm. This is a modest improvement on the result of applying the CHARGE programme to a slightly different set of alcohols. Some alcohol complexes with acetone and acetonitrile were investigated both in the gas phase and in a continuum of the relevant solvent. PMID- 26256676 TI - Morphogenetic characterisation, date of divergence, and evolutionary relationships of malaria vectors Anopheles cruzii and Anopheles homunculus. AB - The mosquito species Anopheles cruzii and Anopheles homunculus are co-occurring vectors for etiological agents of malaria in southeastern Brazil, a region known to be a major epidemic spot for malaria outside Amazon region. We sought to better understand the biology of these species in order to contribute to future control efforts by (1) improving species identification, which is complicated by the fact that the females are very similar, (2) investigating genetic composition and morphological differences between the species, (3) inferring their phylogenetic histories in comparison with those of other Anophelinae, and (4) dating the evolutionary divergence of the two species. To characterise the species we used wing geometry and mitochondrial cytochrome oxidase subunit I (COI) gene as morphological and genetic markers, respectively. We also used the genes white, 28S, ITS2, Cytb, and COI in our phylogenetic and dating analyses. A comparative analysis of wing thin-plate splines revealed species-specific wing venation patterns, and the species An. cruzii showed greater morphological diversity (8.74) than An. homunculus (5.58). Concerning the COI gene, An. cruzii was more polymorphic and also showed higher haplotype diversity than An. homunculus, with many rare haplotypes that were displayed by only a few specimens. Phylogenetic analyses revealed that all tree topologies converged and showed [Anopheles bellator+An. homunculus] and [Anopheles laneanus+An. cruzii] as sister clades. Diversification within the subgenus Kerteszia occurred 2 14.2millionyears ago. The landmark data associated with wing shape were consistent with the molecular phylogeny, indicating that this character can distinguish higher level phylogenetic relationships within the Anopheles group. Despite their morphological similarities and co-occurrence, An. cruzii and An. homunculus show consistent differences. Phylogenetic analysis revealed that the species are not sister-groups but species that recently diverged within the Kerteszia group, perhaps concomitantly with the radiation of bromeliads in South America or during the Pleistocene climate oscillations. PMID- 26256677 TI - Multiscale modeling of the trihexyltetradecylphosphonium chloride ionic liquid. AB - A multiscale modeling protocol was sketched for the trihexyltetradecylphosphonium chloride ([P6,6,6,14]Cl) ionic liquid (IL). The optimized molecular geometries of an isolated [P6,6,6,14] cation and a tightly bound [P6,6,6,14]Cl ion pair structure were obtained from quantum chemistry ab initio calculations. A cost effective united-atom model was proposed for the [P6,6,6,14] cation based on the corresponding atomistic model. Atomistic and coarse-grained molecular dynamics simulations were performed over a wide temperature range to validate the proposed united-atom [P6,6,6,14] model against the available experimental data. Through a systemic analysis of volumetric quantities, microscopic structures, and transport properties of the bulk [P6,6,6,14]Cl IL under varied thermodynamic conditions, it was identified that the proposed united-atom [P6,6,6,14] cationic model could essentially capture the local intermolecular structures and the nonlocal experimental thermodynamics, including liquid density, volume expansivity and isothermal compressibility, and transport properties, such as zero-shear viscosity, of the bulk [P6,6,6,14]Cl IL within a wide temperature range. PMID- 26256678 TI - Up-regulation of the kinin B2 receptor pathway modulates the TGF-beta/Smad signaling cascade to reduce renal fibrosis induced by albumin. AB - The presence of high protein levels in the glomerular filtrate plays an important role in renal fibrosis, a disorder that justifies the use of animal models of experimental proteinuria. Such models have proved useful as tools in the study of the pathogenesis of chronic, progressive renal disease. Since bradykinin and the kinin B2 receptor (B2R) belong to a renoprotective system with mechanisms still unclarified, we investigated its anti-fibrotic role in the in vivo rat model of overload proteinuria. Upon up-regulating the kinin system by a high potassium diet we observed reduction of tubulointerstitial fibrosis, decreased renal expression of alpha-smooth muscle actin (alpha-SMA) and vimentin, reduced Smad3 phosphorylation and increase of Smad7. These cellular and molecular effects were reversed by HOE-140, a specific B2R antagonist. In vitro experiments, performed on a cell line of proximal tubular epithelial cells, showed that high concentrations of albumin induced expression of mesenchymal biomarkers, in concomitance with increases in TGF-beta1 mRNA and its functionally active peptide, TGF-beta1. Stimulation of the tubule cells by bradykinin inhibited the albumin-induced changes, namely alpha-SMA and vimentin were reduced, and cytokeratin recovered together with increase in Smad7 levels and decrease in type II TGF-beta1 receptor, TGF-beta1 mRNA and its active fragment. The protective changes produced by bradykinin in vitro were blocked by HOE-140. The development of stable bradykinin analogues and/or up-regulation of the B2R signaling pathway may prove value in the management of chronic renal fibrosis in progressive proteinuric renal diseases. PMID- 26256679 TI - Cell memory-based therapy. AB - Current cell therapies, despite all of the progress in this field, still faces major ethical, technical and regulatory hurdles. Because these issues possibly stem from the current, restricted, stereotypical view of cell ultrastructure and function, we must think radically about the nature of the cell. In this regard, the author's theory of the cell memory disc offers 'memory-based therapy', which, with the help of immune system rejuvenation, nervous system control and microparticle-based biodrugs, may have substantial therapeutic potential. In addition to its potential value in the study and prevention of premature cell aging, age-related diseases and cell death, memory therapy may improve the treatment of diseases that are currently limited by genetic disorders, risk of tumour formation and the availability and immunocompatibility of tissue transplants. PMID- 26256680 TI - Optimal surgical management of pulmonary metastases: VATS versus thoracotomy. AB - Survival benefit after pulmonary metastasectomy is under question and knowledge of functional recovery after pulmonary metastasectomy by thoracotomy and video assisted thoracoscopic surgery (VATS) is of great importance. We analysed prospective data of 100 patients operated for pulmonary metastasis by either VATS or thoracotomy. VATS yielded a better physical performance 1 month postoperative, shorter hospital stay, a shorter duration of chest tube drainage and epidural analgesia. We concluded that VATS is the preferable approach due to superior functional outcome. PMID- 26256681 TI - Efficient separation of curcumin, demethoxycurcumin, and bisdemethoxycurcumin from turmeric using supercritical fluid chromatography: From analytical to preparative scale. AB - Curcumin is the major constituent of turmeric (Curcuma longa L.). It has attracted widespread attention for its anticancer and anti-inflammatory activities. The separation of curcumin and its two close analogs, demethoxycurcumin and bisdemethoxycurcumin, has been challenging by conventional techniques. In this study, an environmentally friendly method based on supercritical fluid chromatography was established for the rapid and facile separation of the three curcuminoids directly from the methanol extract of turmeric. The method was first developed and optimized by ultra performance convergence chromatography, and was then scaled up to preparative supercritical fluid chromatography. Eluted with supercritical fluid CO2 containing 8-15% methanol (containing 10 mM oxalic acid) at a flow rate of 80 mL/min, curcumin, demethoxycurcumin and bisdemethoxycurcumin could be well separated on a Viridis BEH OBD column (Waters, 250 mm * 19 mm, 5 MUm) within 6.5 min. As a result, 20.8 mg of curcumin (97.9% purity), 7.0 mg of demethoxycurcumin (91.1%), and 4.6 mg of bisdemethoxycurcumin (94.8%) were obtained after a single step of supercritical fluid chromatography separation with a mean recovery of 76.6%. Showing obvious advantages in low solvent consumption, large sample loading, and easy solvent removal, supercritical fluid chromatography was proved to be a superior technique for the efficient separation of natural products. PMID- 26256682 TI - Sustainability of biofuels and renewable chemicals production from biomass. AB - In the sectors of biofuel and renewable chemicals the big feedstock demand asks, first, to expand the spectrum of carbon sources beyond primary biomass, second, to establish circular processing chains and, third, to prioritize product sectors exclusively depending on carbon: chemicals and heavy-duty fuels. Large-volume production lines will reduce greenhouse gas (GHG) emission significantly but also low-volume chemicals are indispensable in building 'low-carbon' industries. The foreseeable feedstock change initiates innovation, securing societal wealth in the industrialized world and creating employment in regions producing biomass. When raising the investments in rerouting to sustainable biofuel and chemicals today competitiveness with fossil-based fuel and chemicals is a strong issue. Many countries adopted comprehensive bioeconomy strategies to tackle this challenge. These public actions are mostly biased to biofuel but should give well balanced attention to renewable chemicals as well. PMID- 26256683 TI - Effects of human amnion-derived mesenchymal stromal cell transplantation in rats with radiation proctitis. AB - BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) have been reported to be a promising cell source in cell therapy, and large amounts of MSCs can easily be isolated from human amnion. Therapeutic irradiation for intra-pelvic cancer often causes radiation proctitis; however, there is currently no effective treatment. We therefore investigated the effect of transplantation of human amnion-derived MSCs (AMSCs) in rats with radiation proctitis. METHODS: Amnion was obtained at cesarean delivery, and AMSCs were isolated and expanded. Sprague-Dawley rats were gamma-irradiated (5 Gy/d) at the rectum for 5 days. On day 5, AMSCs (1 * 10(6) cells) were intravenously transplanted. Rats were killed on day 8. Histological analyses were performed, and messenger RNA expression of inflammatory mediators was measured. In vitro, after gamma-irradiation of rat intestinal epithelial cells (IEC-6), the cells were cultured with AMSC-conditioned medium (CM). The effect of AMSC-CM was evaluated by measurement of caspase-3/7 activity, p53 transcription activity and quantitative reverse-transcription-polymerase chain reaction for p53-target genes. RESULTS: Histological examination demonstrated that epithelial injury and infiltration of inflammatory cells in the rectum were significantly suppressed by transplantation of AMSCs. In vitro, the cell injury in IEC-6 cells induced by gamma-irradiation was inhibited by AMSC-CM, which also inhibited the upregulation of p53 transcription activity, caspase-3/7 activity and p21 expression. CONCLUSIONS: Transplantation of AMSCs improved radiation proctitis, possibly through inhibition of cell injury and inflammatory reactions. AMSC transplantation should be considered as a new treatment for radiation proctitis. PMID- 26256684 TI - Modeling Area-Level Health Rankings. AB - OBJECTIVE: Rank county health using a Bayesian factor analysis model. DATA SOURCES: Secondary county data from the National Center for Health Statistics (through 2007) and Behavioral Risk Factor Surveillance System (through 2009). STUDY DESIGN: Our model builds on the existing county health rankings (CHRs) by using data-derived weights to compute ranks from mortality and morbidity variables, and by quantifying uncertainty based on population, spatial correlation, and missing data. We apply our model to Wisconsin, which has comprehensive data, and Texas, which has substantial missing information. DATA COLLECTION METHODS: The data were downloaded from www.countyhealthrankings.org. PRINCIPAL FINDINGS: Our estimated rankings are more similar to the CHRs for Wisconsin than Texas, as the data-derived factor weights are closer to the assigned weights for Wisconsin. The correlations between the CHRs and our ranks are 0.89 for Wisconsin and 0.65 for Texas. Uncertainty is especially severe for Texas given the state's substantial missing data. CONCLUSIONS: The reliability of comprehensive CHRs varies from state to state. We advise focusing on the counties that remain among the least healthy after incorporating alternate weighting methods and accounting for uncertainty. Our results also highlight the need for broader geographic coverage in health data. PMID- 26256685 TI - MG53 protein: a promising novel therapeutic target for myocardial ischemia reperfusion injury. PMID- 26256686 TI - Long-term outcome prediction of CHA2DS2VASc and HATCH scores in a cohort of patients with typical atrial flutter. PMID- 26256687 TI - Post-cardiac surgery Takotsubo syndrome: another thing to keep in mind. PMID- 26256688 TI - Intramedullary megakaryocytes internalize released platelet factor 4 and store it in alpha granules. AB - BACKGROUND: Megakaryocytes express and store platelet factor 4 (PF4) in alpha granules. In vivo, PF4 is a clinically relevant, negative regulator of megakaryopoiesis and hematopoietic stem cell replication. These findings would suggest a regulated source of free intramedullary PF4. OBJECTIVES: Define the source of free intramedullary PF4 and its intramedullary life cycle. METHODS: We interrogated both murine and human bone marrow-derived cells during megakaryopoiesis in vitro by using confocal microscopy and enzyme-linked immunosorbent assay. With immunohistochemistry, we examined in vivo free PF4 in murine bone marrow before and after radiation injury and in the setting of megakaryocytopenia and thrombocytopenia. RESULTS: Exogenously added human PF4 is internalized by murine megakaryocytes. Human megakaryocytes similarly take up murine PF4 but not the related chemokine, platelet basic protein. Confocal microscopy shows that internalized PF4 colocalizes with endogenous PF4 in alpha granules and is available for release on thrombin stimulation. Immunohistochemistry shows free PF4 in the marrow, but not another alphagranule protein, von Willebrand factor. Free PF4 increases with radiation injury and decreases with megakaryocytopenia. Consistent with the known role of low-density lipoprotein receptor-related protein 1 in the negative paracrine effect of PF4 on megakaryopoiesis, PF4 internalization is at least partially low-density lipoprotein receptor-related protein 1 dependent. CONCLUSIONS: PF4 has a complex intramedullary life cycle with important implications in megakaryopoiesis and hematopoietic stem cell replication not seen with other tested alpha granule proteins. PMID- 26256689 TI - FgCDC14 regulates cytokinesis, morphogenesis, and pathogenesis in Fusarium graminearum. AB - Members of Cdc14 phosphatases are common in animals and fungi, but absent in plants. Although its orthologs are conserved in plant pathogenic fungi, their functions during infection are not clear. In this study, we showed that the CDC14 ortholog is important for pathogenesis and morphogenesis in Fusarium graminearum. FgCDC14 is required for normal cell division and septum formation and FgCdc14 possesses phosphatase activity with specificity for a subset of Cdk-type phosphorylation sites. The Fgcdc14 mutant was reduced in growth, conidiation, and ascospore formation. It was defective in ascosporogenesis and pathogenesis. Septation in Fgcdc14 was reduced and hyphal compartments contained multiple nuclei, indicating defects in the coordination between nuclear division and cytokinesis. Interestingly, foot cells of mutant conidia often differentiated into conidiogenous cells, resulting in the production of inter-connected conidia. In the interphase, FgCdc14-GFP localized to the nucleus and spindle-pole-body. Taken together, our results indicate that Cdc14 phosphatase functions in cell division and septum formation in F. graminearum, likely by counteracting Cdk phosphorylation, and is required for plant infection. PMID- 26256690 TI - Synchronous mantle cell lymph node lymphoma and pulmonary adenocarcinoma: a case report with literature review. AB - BACKGROUND AND AIMS: Coexistence of mantle cell lymphoma and lung adenocarcinoma is extremely rare. The aim of this study is to present the first case of incidental discovery of primary lung adenocarcinoma associated to lymph node mantle cell lymphoma. METHODS: A 45 year-old man, admitted for inguinal mass appeared since three months. Physical examination showed a 1 cm axillary and 3 cm inguinal adenopathies which were hard and fixed. A biopsy of inguinal mass revealed mantle cell lymphoma. Assessment of disease extension found a right superior lobe tumor with mediastinal lymphadenopathies. Fibreoptic bronchoscopy was normal. A fine needle biopsy of lung tumor was performed to determinate the nature of the pulmonary lesion. Histopathological findings were consistent with primary poor differentiated pulmonary adenocarcinoma with TTF-1 expression. A first mediastinoscopy was realized to verify mediastinal lymphadenopathies; frozen section showed a mantle cell lymphoma. A right lobectomy was then performed confirming the diagnosis of lung adenocarcinoma. Then, the patient was treated for the mantle cell lymphoma by 6 cures of alternating RCHOP and RDHAP (dexamethasone, high-dose Ara-Cytarabine and cisplatin) regimens followed by autologous stem cell transplantation. RESULTS: The patient died because of treatment complications 3 years after diagnosis. CONCLUSION: Progresses are necessary to understand the pathogenesis of of synchronous occurrence of both diseases. PMID- 26256691 TI - The proteomic analysis improved by cleavage kinetics-based fractionation of tryptic peptides. AB - Selective enrichment of specific peptides is an effective way to identify low abundance proteins. Fractionation of peptides prior to mass spectrometry is another widely used approach to reduce sample complexity in order to improve proteome coverage.In this study, we designed a multi-stage digestion strategy to generate peptides with different trypsin cleavage kinetics. It was found that each of the collected peptide fractions yielded many new protein identifications compared to the control group due to the reduced complexity. The overlapping peptides identified between adjacent fractions were very low, indicating that each fraction had different sets of peptides. The multi-stage digestion strategy separates tryptic peptides with different cleavage kinetics while RPLC separates peptides with different hydrophobicity. These two separation strategies were highly orthogonal, and showed an effective multidimensional separation to improve proteome coverage. PMID- 26256692 TI - The clinical impact of vancomycin-resistant Enterococcus colonization and bloodstream infection in patients undergoing autologous transplantation. AB - BACKGROUND: Although several studies have documented adverse outcomes for vancomycin-resistant Enterococcus (VRE) colonization and infection in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, data are inadequate for patients undergoing autologous (auto-)HSCT. METHODS: We conducted a retrospective cohort study of 300 consecutive patients receiving an auto-HSCT between 2006 and 2014. Patients had stool cultures for VRE on admission and weekly during hospitalization. RESULTS: Thirty-six percent of patients had VRE gastrointestinal (GI) colonization and 3% developed a VRE bloodstream infection (BSI), all of whom were colonized. VRE strain typing of BSI isolates showed that some patients shared identical patterns. Rates of colonization and BSI in colonized patients were similar to simultaneous patients undergoing allo-HSCT, except that the latter had a higher rate of colonization at admission. A diagnosis of lymphoma was associated with an increased risk of colonization. VRE BSI was associated with longer lengths of stay and possibly higher costs, but no decrease in overall survival, and colonized patients had no VRE infections during the year following discharge. Repeat stool cultures in patients subsequently undergoing allo-HSCT suggested that most, if not all, VRE-positive auto-HSCT patients lose their detectable GI colonization within a few months of discharge. CONCLUSION: VRE colonization is frequent but carries a low risk for infection in patients undergoing auto-HSCT. However, these patients can serve as reservoirs for transmission to higher risk patients. Moreover, patients may remain colonized if proceeding to an allo-HSCT shortly after auto-HSCT, potentially increasing the risk of the allogeneic procedure. PMID- 26256693 TI - Anomalously Rapid Hydration Water Diffusion Dynamics Near DNA Surfaces. AB - The emerging Overhauser effect dynamic nuclear polarization (ODNP) technique measures the translational mobility of water within the vicinity (5-15 A) of preselected sites. The work presented here expands the capabilities of the ODNP technique and illuminates an important, previously unseen, property of the translational diffusion dynamics of water at the surface of DNA duplexes. We attach nitroxide radicals (i.e., spin labels) to multiple phosphate backbone positions of DNA duplexes, allowing ODNP to measure the hydration dynamics at select positions along the DNA surface. With a novel approach to ODNP analysis, we isolate the contributions of water molecules at these sites that undergo free translational diffusion from water molecules that either loosely bind to or exchange protons with the DNA. The results reveal that a significant population of water in a localized volume adjacent to the DNA surface exhibits fast, bulk like characteristics and moves unusually rapidly compared to water found in similar probe volumes near protein and membrane surfaces. Control studies show that the observation of these characteristics are upheld even when the DNA duplex is tethered to streptavidin or the mobility of the nitroxides is altered. This implies that, as compared to protein or lipid surfaces, it is an intrinsic feature of the DNA duplex surface that it interacts only weakly with a significant fraction of the surface hydration water network. The displacement of this translationally mobile water is energetically less costly than that of more strongly bound water by up to several kBT and thus can lower the activation barrier for interactions involving the DNA surface. PMID- 26256694 TI - Exploring the relationship between object realism and object-based attention effects. AB - Visual attention prioritizes processing of locations in space, and evidence also suggests that the benefits of attention can be shaped by the presence of objects (object-based attention). However, the prevalence of object-based attention effects has been called into question recently by evidence from a large-sampled study employing classic attention paradigms (Pilz et al., 2012). We conducted two experiments to explore factors that might determine when and if object-based attention effects are observed, focusing on the degree to which the concreteness and realism of objects might contribute to these effects. We adapted the classic attention paradigm first reported by Egly, Driver, and Rafal (1994) by replacing abstract bar stimuli in some conditions with objects that were more concrete and familiar to participants: items of silverware. Furthermore, we varied the realism of these items of silverware, presenting either cartoon versions or photo realistic versions. Contrary to predictions, increased realism did not increase the size of object-based effects. In fact, no clear object-based effects were observed in either experiment, consistent with previous failures to replicate these effects in similar paradigms. While object-based attention may exist, and may have important influences on how we parse the visual world, these and other findings suggest that the two-object paradigm typically relied upon to study object-based effects may not be the best paradigm to investigate these issues. PMID- 26256695 TI - Simple procedure applying lactose induction and one-step purification for high yield production of rhCIFN. AB - Recombinant consensus interferon (CIFN) is a therapeutic protein with molecular weight of 19.5 kDa having broad spectrum antiviral activity. Recombinant human CIFN (rhCIFN) has previously been expressed in Escherichia coli using isopropyl beta-d-thiogalactopyranoside (IPTG), a non-metabolizable and expensive compound, as inducer. For economical and commercial-scale recombinant protein production, it is greatly needed to increase the product yield in a limited time frame to reduce the processing cost. To reduce the cost of production of rhCIFN in E. coli, induction was accomplished by using lactose instead of IPTG. Lactose induction (14 g/L) in shake flask experiment resulted in higher yield as compared with 1 mM IPTG. Finally, with single-step purification on DEAE sepharose, 150 mg/L of >98% pure rhCIFN was achieved. In the present study, an attempt was made to develop a low cost process for producing quality product with high purity. Methods devised may be helpful for pilot-scale production of recombinant proteins at low cost. PMID- 26256696 TI - Comparative effect of two pan-class I PI3K inhibitors used as anticancer drugs on human T cell function. AB - The phosphatidylinositol 3-kinase (PI3K) pathway is commonly deregulated in cancer and, thus, PI3K has been recognized as an attractive molecular target for novel anti-cancer therapies. However, the effect of PI3K inhibitors on T-cell function, a key component of antitumor immunity, has been scantly explored. The objective of this study was to investigate the effect on human T-cell activation of two PI3K inhibitors currently being tested in clinical trials: PX-866 and BKM120. Their activity against a leukemic T cell line was also assessed. For that purpose, Jurkat cells or anti-CD3/anti-CD28 stimulated human peripheral blood mononuclear cells were cultured in the presence of different concentrations of PX 866 or BKM120 and their effect on T-cell proliferation, apoptosis, expression of activation markers and cytokine secretion was analyzed by flow cytometry. In addition, Akt and Erk phosphorylation was analyzed by Western blotting. Both PX 866 and BKM120 decreased viability of Jurkat cells and blocked cell cycle progression. Regarding primary T cells, both compounds similarly inhibited expression of activation markers and cytokine secretion, although they did not induce apoptosis of stimulated T cells. Interestingly, we found differences in their ability to block T-cell proliferation and IL-2 secretion, exerting BKM120 a more potent inhibition. These disparate effects could be related to differences observed in PI3K/Akt and RAS/MEK/ERK signaling between PX-866 and BKM120 treated cells. Our results suggest that, when selecting a PI3K inhibitor for cancer therapy, immunosuppressive characteristics should be taken into account in order to minimize detrimental effects on immune function. PMID- 26256697 TI - Molecular cloning, expression and bioactivity of B cell activating factor (BAFF) in African ostrich. AB - B cell activating factor (BAFF), which belongs to the tumor necrosis factor (TNF) family, is testified to play a critical role in B cell survival, proliferation, maturation and immunoglobulin secretion. In the present study, the cDNA of open reading frame (ORF) in African ostrich (Struthio camelus) BAFF (designated OsBAFF) was cloned by reverse transcription-PCR (RT-PCR). The OsBAFF gene encodes a 288-amino acid protein containing a predicted transmembrane domain and a putative furin protease cleavage site like BAFFs from chicken (cBAFF), quail (qBAFF), duck (dBAFF), goose (gBAFF) and dove (doBAFF). RT-PCR analysis showed that the OsBAFF gene is strongly expressed in the bursa of Fabricius, thymus, spleen, and bone marrow. The soluble OsBAFF had been cloned into pET28a. SDS-PAGE and Western blotting analysis confirmed that the soluble fusion protein His OsBAFF was efficiently expressed in Escherichia coli Rosset (DE3). In vitro, purified OsBAFF was not only able to promote the survival of African ostrich bursal lymphocytes, but also able to co-stimulate proliferation of mouse splenic B cells. The expression of OsBAFF in lymphocyte cells was higher than the control after LPS stimulation. These findings indicated that OsBAFF plays an important role in survival and proliferation of African ostrich bursal lymphocytes, which may provide valuable information for research into the immune system of African ostrich and OsBAFF may serve as a potential immunologic factor for enhancing immunological efficacy in African ostrich and any other birds. PMID- 26256698 TI - Lactoferrin suppresses lipopolysaccharide-induced endometritis in mice via down regulation of the NF-kappaB pathway. AB - Lactoferrin (LF) is one of the most abundant proteins found in milk, and it has been reported to have anti-inflammatory properties. However, the anti inflammatory effects of LF on lipopolysaccharide (LPS)-induced endometritis and the underlying molecular mechanisms remain to be elucidated. In this study, we evaluated the effects of LF on LPS-induced endometritis in mice. The endometritis model was established by the perfusion of mice with LPS. LF was administered by intraperitoneal injection 1h before and 12h after LPS induction. Our results demonstrated that LF significantly attenuated the histopathological changes in the uterus, reduced the activity of myeloperoxidase (MPO) and the levels of nitric oxide (NO), and inhibited the activation of NF-kappaB and the expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in a dose-dependent manner. The results suggest that LF has an anti-inflammatory effect on LPS-induced endometritis in mice. Therefore, LF may be a potential therapeutic agent for the treatment of endometritis. PMID- 26256699 TI - Anti-inflammatory effects of vina-ginsenoside R2 and majonoside R2 isolated from Panax vietnamensis and their metabolites in lipopolysaccharide-stimulated macrophages. AB - Panax vietnamensis Ha et Grushv., with its main constituents vina-ginsenoside R2 (VR2) and majonoside R2 (MR2), is used in traditional folk medicine in the hill tribes of Vietnam for anti-fatigue, anti-inflammatory, and life-saving purposes. In a preliminary study, VR2 and MR2 were shown to be metabolized to pseudoginsenoside RT4 (PRT4) and ocotillol by human gut microbiota. Therefore, we measured the anti-inflammatory effects of VR2, MR2, and their metabolites in lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophages. Among these ginsenosides, only VR2 exhibited cytotoxicity against peritoneal macrophages. MR2, PRT4, and ocotillol inhibited LPS-stimulated transcription factor (NF) kappaB activation, and expression of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin (IL)-1. However, these ginsenosides did not inhibit peptidoglycan-induced NF-kappaB activation in the macrophages. These three ginsenosides also inhibited LPS-stimulated cyclooxygenase-2 and inducible NO synthase expression, and phosphorylation of NF-kappaB signal molecules IL-1 receptor-associated kinase 1 and tumor growth factor-beta-activated kinase 1 in peritoneal macrophages. Treatment with either PRT4 or ocotillol inhibited the Alexa Fluor 488-conjugated LPS-mediated shift of macrophages, as observed by flow cytometry. They also potently inhibited the binding of LPS to TLR4 on peritoneal macrophages, both with and without transfected MyD88 siRNA. Among the tested ginsenosides, ocotillol exhibited the strongest inhibitory effect on inflammation in LPS-stimulated macrophages via the NF-kappaB signaling pathway. Based on these findings, orally administered VR2 and MR2 of P. vietnamensis may be metabolized to ocotillol via PRT4, and the metabolites, particularly ocotillol, may inhibit inflammation by inhibiting the binding of LPS to TLR4 on macrophages. PMID- 26256700 TI - Reduced perfusion in normal-appearing white matter in mild to moderate hypertension as revealed by 3D pseudocontinuous arterial spin labeling. AB - PURPOSE: To investigate the hemodynamic changes of normal-appearing white matter (NAWM) in hypertension using the 3D pseudocontinuous arterial spin labeling (pCASL) technique. MATERIALS AND METHODS: Seventy-three subjects, including a patient group (n = 41; 30 males; age = 47.7 +/- 8.3 years; test-time blood pressure [BP] = 155 +/- 23/98 +/- 11 mmHg) and an age-matched control group (n = 32; 14 males; age = 46 +/- 8.3 years; test-time BP = 117 +/- 8/76 +/- 10 mmHg), were recruited and scanned on a 3.0T magnetic resonance imaging (MRI) system using routine MRI sequences and 3D pCASL sequence. The routine MRI sequences were used to further define the NAWM. The cerebral blood flow (CBF) values in various regions of interest (ROIs) were extracted. One-way analysis of variance (ANOVA) and unpaired t-test were performed to evaluate the significance of the intergroup difference in CBF modifications. RESULTS: Compared to healthy volunteers, CBF values in global gray matter (GM) and various NAWM regions were found to be lower (P < 0.05) in hypertensive patients, except for genu of corpus callosum (CC), cingulate gyrus, amygdala, pallidum, putamen, and thalamus (P > 0.05). Furthermore, compared to the control group, mild hypertension showed significantly reduced CBF in various ROIs (P < 0.05), but no intergroup differences in GM, R anterior horn of periventricular WM, and genu of CC (P > 0.05), while moderate hypertension showed reduced CBF in all ROIs (P < 0.05). However, it was observed that, between mild and moderate hypertensive patients, there were no statistically significant difference in CBF values except for genu of CC (P < 0.05). CONCLUSION: 3D pCASL has the ability to detect subtle hemodynamic abnormalities in NAWM regions at relatively early stages of hypertension. The observed decreases in CBF in these regions may suggest an increased risk of cerebral small vessel diseases. PMID- 26256701 TI - Series of Noncontrast Time-of-Flight Magnetic Resonance Angiographies to Identify Problems with Arteriovenous Fistula Maturation. AB - BACKGROUND: Successful maturation of arteriovenous fistulas (AVFs) remains a challenge for those managing patients with end-stage renal disease. Time-of flight magnetic resonance angiography (TOF-MR) can be used to evaluate AVFs without the risk of radiation exposure, intravenous contrast, or reliance on the operator-dependent modality of color Doppler ultrasonography (CDUS). The objective of our study was to assess the utility of TOF-MR in the evaluation of nonmaturing AVFs and to identify the best clinical situations to use this technology. METHODS: Consecutive patients with abnormal findings on CDUS or physical examination after AVF creation underwent 3-dimensional (3D) TOF-MR. Imaging was performed at 3 T with a scan acquisition time of approximately 15 min. The technique was similar to head and neck magnetic resonance angiography (MRA), except presaturation bands were not used, thereby allowing simultaneous visualization of both arterial and venous flow. A total of 19 TOF-MR studies were performed. RESULTS: Nineteen patients underwent imaging and were the focus of this study. Seventeen of 19 TOF-MR studies were of diagnostic quality and yielded findings which enabled the vascular surgeon to take corrective measures. Findings included inflow stenosis, anastomotic narrowing, venous outflow stenosis, and hemodynamically significant venous tributaries. Twelve of 17 patients required conventional digital subtraction angiography (DSA). The congruence rate between TOF-MR and DSA was 83.3%. Four patients (21%) avoided DSA and went directly to definitive surgical treatment including branch ligation (3) or new access (1). CONCLUSIONS: This is the first report in the literature of successful implementation of 3D TOF-MR to assist in identifying AVF maturation problems. This unique noninvasive imaging modality provides actionable images without contrast or radiation exposure and can obviate the need for invasive diagnostic procedures or provide an anatomic map for planning corrective intervention. PMID- 26256702 TI - Ten-Year Experience of Vascular Surgeon Management of Iatrogenic Pseudoaneurysms: Do Anticoagulant and/or Antiplatelet Medications Matter? AB - BACKGROUND: Previous studies examining the natural history of femoral pseudoaneurysms (PSAs) were performed before the current era of anticoagulant and/or antiplatelet therapy. The purpose of our study was to elucidate in a vascular surgeon directed approach to PSAs, the association between medication use and the failure of conservative, observation-only management. METHODS: We retrospectively examined 308 femoral iatrogenic PSAs diagnosed via duplex imaging at our institution during a 10-year time period (2004-2013). Information on PSA characteristics, treatment, and antiplatelet and/or anticoagulant medication usage was obtained. We identified patients who failed observation-only conservation management, with failure defined as the need for delayed treatment because of PSAs triggered by either expansion (>= 1 cm increase or size enlarging to >= 3 cm) and/or persistence (>= 15 days). RESULTS: Immediate and/or acute treatments of PSAs included 1 ultrasound-guided compression, 14 surgical repairs, and 126 thrombin injections. Of the 167 PSAs initially managed by observation only, 70 (42%) were found by ultrasound imaging to thrombosis spontaneously. An additional 70 (42%) patients had the diagnosis of PSA <3 cm and were managed conservatively with only clinical follow-up. Twenty-seven PSAs (16%) originally managed conservatively required additional treatment because of expansion and/or persistence. Patients receiving dual-antiplatelet therapy had higher rates of failed conservative management (44%) than patients not on dual therapy (9%, P < 0.01). The number of antiplatelet and/or anticoagulant medications used during observation was larger in patients failing conservative management (2.0 +/- 0.7) versus patients not requiring additional intervention (1.5 +/- 0.7, P < 0.01). CONCLUSIONS: Most of the PSAs initially managed with observation-only did not require additional intervention. However, anticoagulant and/or antiplatelet agents use associated with PSAs required further intervention after failing observation-only management. When observation is the chosen strategy for PSA management, especially in the setting of aggressive antithrombotic and dual antiplatelet therapy, surveillance is required to ensure proper resolution. PMID- 26256703 TI - Combined Coronary Artery Bypass Grafting and Abdominal Aortic Aneurysm Repair: Presentation of 3 Cases and a Review of the Literature. AB - BACKGROUND: Coronary artery disease and abdominal aortic aneurysmal disease can occur in a single patient, and a therapeutic conundrum presents when open surgical repair is indicated for both conditions. The traditional standard of care is to conduct coronary artery bypass grafting (CABG) followed by abdominal aortic aneurysm (AAA) repair 2-6 months later, but there is significant risk with staging these 2 major surgeries. An alternative method is to surgically repair both diseases in 1 combined operation. The aim of our study is to review our own experience with the combined procedure and to review the published literature to assess morbidity and mortality of combined CABG and AAA repair. METHODS: A systematic search for relevant studies was performed in the PubMed/Medline database. Short-term mortality (<30 days) and postoperative complications were assessed from relevant case series from 1993 to 2013. We also conducted a retrospective chart review of all patients undergoing the combined procedure at our institution. RESULTS: Thirty case series with a total of 369 patients averaged a 30-day mortality of 3.0%. Fourteen percent and 6% of patients experienced a cardiovascular or respiratory complication, respectively. Other postoperative events included acute renal failure (7%) and superficial wound complications (5%). In our own experience, 3 patients underwent combined CABG and AAA repair. The mean age was 71 years, the average AAA size was 8.9 cm, and average operative time was 328 min. None experienced any postoperative complications. Two are still alive at 9 and 10 years after surgery, and 1 died of unrelated causes 8 years postoperatively. CONCLUSIONS: The results of this systematic review suggest that combined CABG and AAA repair is a viable procedure with low operative mortality. Patients with preserved ejection fractions, large AAA, and limited comorbidities appear to receive the most benefit from a combined approach based on reported data from the literature. We have experienced promising results in our highly selected patient population. More research is warranted to devise criteria to determine which patients would be good surgical candidates for this combined procedure. PMID- 26256704 TI - Value of C-Arm Cone Beam Computed Tomography Image Fusion in Maximizing the Versatility of Endovascular Robotics. AB - BACKGROUND: To report our initial experience and highlight the value of using intraoperative C-arm cone beam computed tomography (CT; DynaCT((r))) image fusion guidance along with steerable robotic endovascular catheter navigation to optimize vessel cannulation. METHODS: Between May 2013 and January 2015, all patients who underwent endovascular procedures using DynaCT image fusion technique along with Hansen Magellan vascular robotic catheter were included in this study. As a part of preoperative planning, relevant vessel landmarks were electronically marked in contrast-enhanced multi-slice computed tomography images and stored. At the beginning of procedure, an intraoperative noncontrast C-arm cone beam CT (syngo DynaCT((r)), Siemens Medical Solutions USA Inc.) was acquired in the hybrid suite. Preoperative images were then coregistered to intraoperative DynaCT images using aortic wall calcifications and bone landmarks. Stored landmarks were then overlaid on 2-dimensional (2D) live fluoroscopic images as virtual markers that are updated in real-time with C-arm, table movements and image zoom. Vascular access and robotic catheter (Magellan((r)), Hansen Medical) was setup per standard. Vessel cannulation was performed based on electronic virtual markers on live fluoroscopy using robotic catheter. The impact of 3 dimensional (3D) image fusion guidance on robotic vessel cannulation was evaluated retrospectively, by assessing quantitative parameters like number of angiograms acquired before vessel cannulation and qualitative parameters like accuracy of vessel ostium and centerline markers. RESULTS: All 17 vessels were cannulated successfully in 14 patients' attempted using robotic catheter and image fusion guidance. Median vessel diameter at origin was 5.4 mm (range, 2.3-13 mm), whereas 12 of 17 (70.6%) vessels had either calcified and/or stenosed origin from parent vessel. Nine of 17 vessels (52.9 %) were cannulated without any contrast injection. Median number of angiograms required before cannulation was 0 (range, 0-2). On qualitative assessment, 14 of 15 vessels (93.3%) had grade = 1 accuracy (guidewire inside virtual ostial marker). Fourteen of 14 vessels had grade = 1 accuracy (virtual centerlines that matched with the actual vessel trajectory during cannulation). CONCLUSIONS: In this small series, the experience of using DynaCT image fusion guidance together with a steerable endovascular robotic catheter indicates that such image fusion strategies can enhance intraoperative 2D fluoroscopy by bringing preoperative 3D information about vascular stenosis and/or calcification, angulation, and take off from main vessel thereby facilitating ultimate vessel cannulation. PMID- 26256705 TI - Heparin-Bonded Polytetrafluorethylene Does Not Improve Hemodialysis Arteriovenous Graft Function. AB - BACKGROUND: Heparin-bonded polytetrafluorethylene (hep PTFE), when compared with standard PTFE, has been shown to have a modest improvement in distal extremity bypass grafts. The data supporting its usage for dialysis access are less clear. We compared the patency rates, number of interventions, and complications between hep PTFE grafts and nonheparin-bonded PTFE (nonhep PTFE) grafts placed for dialysis access. METHODS: A retrospective review of all dialysis access procedures between January 2013 and March 2014 entered into a prospectively maintained vascular surgery database was performed. Our primary end point was functional graft patency. Secondary end points were primary, primary assisted, and secondary patency, as well as time to graft abandonment, and number of procedures required to maintain or restore graft patency. The number of interventions required to maintain graft patency and graft-related complications were also reviewed. Kaplan-Meier curves were used to compare the 2 groups. RESULTS: Between January 2013 and March 2014, 301-dialysis access procedures were performed, which included 70 arteriovenous grafts (AVGs) comprised 32 hep PTFE (32, 6-mm straight grafts) and 38 nonhep PTFE (35, 4-7-mm taper and 3, 6-mm straight). Mean follow-up was 7.35 +/- 5.15 months. At 1 year, Kaplan-Meier survival curves showed that functional patency between hep PTFE and nonhep PTFE AVG were 60% and 75%, respectively (P = 0.37). Primary and secondary patencies were not significantly different between groups; however, primary-assisted patency was significantly improved at 1 year (hep PTFE versus nonhep PTFE: 50% vs. 80%; P = 0.02). The number of hep PTFE grafts undergoing percutaneous thrombectomy was significantly higher than the nonhep PTFE grafts (11 vs. 2; P = 0.009). The incidence and time to graft abandonment were not statistically different. The same was true for the number of complications between the 2 groups. Multivariate analysis showed nonhep PTFE AVG to be advantageous for primary and primary-assisted patency. CONCLUSIONS: We did not demonstrate a benefit to the routine use of hep PTFE for AVG creation especially given the higher cost of these grafts. Functional patency rates were not improved, and the rates of reintervention and thrombectomy were higher with hep PTFE AVGs. PMID- 26256706 TI - Pneumatic Compression Improves Quality of Life in Patients with Lower-Extremity Lymphedema. AB - BACKGROUND: Lymphedema is an incurable and disfiguring disease secondary to excessive fluid and protein in the interstitium as a result of lymphatic obstruction. Pneumatic compression (PC) offers a novel modality for treatment of lymphatic obstruction through targeting lymphatic beds and mimicking a functional drainage system. The objective of this study is to demonstrate improved quality of life in patients with lower-extremity lymphedema. METHODS: Consecutive patients presenting to a single institution for treatment of lymphedema were all treated with PC for at least 3 months. All patients underwent a pre- and post-PC assessment of episodes of cellulitis, number of ulcers, and venous insufficiency. Post-PC symptom questionnaires were administered. Symptom improvement was the primary outcome for analysis. RESULTS: A total of 100 patients met inclusion criteria. At presentation, 70% were female with a mean age of 57.5 years. Secondary lymphedema was present in 78%. Mean length of PC use was 12.7 months with a mean of 5.3 treatments per week. Ankle and calf limb girth decreased after PC use, (28.3 vs. 27.5 cm, P = 0.01) and (44.7 vs. 43.8 cm, P = 0.018), respectively. The number of episodes of cellulitis and ulcers pre- and post-PC decreased from mean of 0.26-0.05 episodes (P = 0.002) and 0.12-0.02 ulcers (P = 0.007), respectively. Fourteen percent had concomitant superficial venous insufficiency, all of whom underwent venous ablation. Overall 100% of patients reported symptomatic improvement post-PC with 54% greatly improved. 90% would recommend the treatment to others. CONCLUSIONS: PC improves symptom relief and reduces episodes of cellulitis and ulceration in lower-extremity lymphedema. It is well tolerated by patients and should be recommended as an adjunct to standard lymphedema therapy. Screening for venous insufficiency is recommended. PMID- 26256707 TI - Management of Vascular Injury during Current Peaceful Yemeni Revolution. AB - BACKGROUND: To provide a complete review of our experience on the observed vascular injuries patterns during contemporary Yemeni revolution, management strategies used in the care of injuries and to highlight lessons learned from that period. METHODS: From February 2011 to January 2012, all casualties evaluated at Yemen International Hospital, were prospectively entered into a database and retrospectively reviewed. Data collected included site, type, and mechanism of vascular injury, associated trauma, type of vascular repair; initial outcome, amputation rate, and complication. RESULTS: Of 2,200 injured patients evacuated from field hospital, vascular injuries occurred in 63 patients, and these patients comprised the study group. Fifty-one (80.9%) patients were wounded by gunshots high velocity, 6 (9.5%) were wounded by gunshots low velocity, and 6 (9.5%) experienced explosive devices injury. Most of injuries 55 (87%) occurred in the extremities 45 (71%) in the lower extremities and 10 (16%) in the upper extremities, 3 (5%) in carotid arteries, 3 (5%) in internal iliac arteries, and 2 (3%) in internal jugular vein. Nearly half 31 (49%) of the patients sustained complex vascular injuries (arterial and venous injuries), isolated arterial injuries 28 (45%), and isolated venous injuries 4 (6%). Twenty (32%) of the patients underwent complete revascularization and 11 (15%) just arterial repair with venous ligation. According arterial management 32 (51%) of patients underwent revascularization with venous graft, 18 (29%) repaired by end-to-end anastomosis, 1 (2%) polytetrafluorethylene, 7 (11%) thrombectomy, and 5 (8%) arterial ligation. Vascular injuries were associated with bony fracture in 33 (52%) of patients. Postoperative wound infection occurred in 9 (14%) patients. Of those, 7 had venous ligation. Secondary amputation and mortality rates during the study period were 3 (5%) and 4 (6%), respectively. CONCLUSIONS: This report represents the first analysis of vascular injuries during contemporary Yemeni revolution in Taiz city. Vascular injuries occurred in 3% of revolution-related injured patients. Our secondary amputation rate of extremities was 5%. Management of arterial repair with autologous vein graft remains the treatment of choice. Ligation of venous injured in a watershed area, such an iliofemoral and popliteal vein should be avoided to prevent leg phlegmasia. PMID- 26256708 TI - The Effect of Ovation Stent-Graft System on Aortic Pulse Wave Velocity: Preliminary Report on 3 Cases. AB - BACKGROUND: The Ovation Aortic Stent-Graft System is based on a pair of polymer filled inflatable O-rings to achieve sealing at the infrarenal level. However, this O-rings inflation has been associated with restriction of flow lumen and regional stenosis up to ~60%. Since the aortic pulse wave velocity (aPWV) is considered a valuable marker of aorta stiffening we investigated the influence of the O-rings induced aortic lumen stenosis on the aPWV during the early postoperative period in a sample of 3 patients. METHODS: The internal cross sectional area and the corresponding radius at the level immediately caudally to the renal arteries (Aupper and Rupper) and at the site of the inflated O-rings (Aint and Rint) was calculated from postoperative images of Computed tomography using dedicated software (3Mensio Medical Imaging B.V., Bilthoven, The Netherlands). Accordingly, the difference in the previously mentioned parameters between these areas was recorded. Noninvasive estimation of aPWV was conducted preoperatively and at 1-week and 1-month postoperatively with a brachial cuff based automatic oscillometric device (Mobil-O-Graph; IEM, Stolberg, Germany). RESULTS: Aupper was 286, 385, and 286 mm(2) for the 3 patients with Aint being 116, 86 and 95 mm(2), corresponding to inflow stenosis of 60%, 75%, and 66%, respectively. Accordingly, the radius reduction of the lumen between Rupper and Rint was 35%, 50%, and 60%. aPWV was kept quite constant for all patients 1-week and 1-month postoperatively, ranging 13.2-13.7, 11.4-11.5, and 8.3-8.6 m/sec, respectively. CONCLUSIONS: The inflow restriction caused by the stiff, inflatable O-rings does not necessarily coincide with significant increase of aortic stiffness in the early postoperative period. Furthermore studies with more hemodynamic indices and longer follow-up are needed to delineate the impact of the Ovation's unique structural pattern on central hemodynamics. PMID- 26256709 TI - U Stent-Graft Technique as a Treatment for Homolateral Metachronous Common Iliac and Internal Iliac Arteries Aneurysms after Open Surgery. AB - We report a case of a metachronous common iliac artery and the internal iliac artery (IIA) aneurysm developed 8 years after an aortobi-femoral bypass for treatment of abdominal aortic aneurysm associated at chronic occlusion of the right iliac axis. To exclude the metachronous aneurysm on the left iliac axis and to maintain the pelvic circulation, an external to IIA endografts were positioned ("U stent-graft technique"). At 6-month follow-up, the computed tomography scan showed patency of the endografts, of the bypass and of the IIA, without endoleak, or other adverse events. PMID- 26256710 TI - A Multicenter, Retrospective Study of the Effectiveness of the Trellis-8 System in the Treatment of Proximal Lower-Extremity Deep Vein Thrombosis. AB - BACKGROUND: Deep vein thrombosis (DVT) occurs in up to 600,000 patients in the United States annually and can lead to long-term morbidity because of the post thrombotic syndrome. The multicenter isolated-pharmacomechanical thrombolysis device (ISOL-8) study was designed to determine the safety and efficacy of the TrellisTM-8 peripheral infusion system when used as the primary intervention to achieve DVT thrombolysis in patients with proximal lower-extremity occlusive DVT, and track the incidence and severity of the post-thrombotic syndrome (PTS) symptoms in patients 2 years after treatment. METHODS: Data were collected retrospectively from 6 centers on patients treated with the Trellis-8 system, an isolated-pharmacomechanical thrombolysis device (IPMTD). Patients with occlusive lower-extremity DVT involving at least the iliac and/or common femoral vein were included. Patient demographics, medical history, procedure outcomes, complications, and follow-up venous duplex and Venous Clinical Severity Score (VCSS) were collected through 24 months. Data analysis of outcomes were performed at 1 and 12 months. A 24-month analysis was not performed because of the small number of patients for whom 24-month data could be collected. RESULTS: A total of 151 limbs in 139 patients were treated with IPMTD. The mean +/- standard deviation (SD) procedure time was 122.6 +/- 63.4 min. Single session treatment was delivered in 69.9% (93 of 133) of cases. Occlusive DVT extended from the femoral into the external and/or common iliac vessel segments in most of the cases (113 of 151 limbs; 74.8%). Before treatment, 23.2% (35 of 151) of the treated limbs, based on a history of prior ipsilateral DVT or preoperative imaging revealing chronic venous scar, were expected to have some chronic venous disease despite presenting with acute symptoms. After treatment, 43.7% (66 of 151) of the limbs showed evidence of chronic thrombus. The average amount (mean +/- SD) of thrombolysis, as determined by venogram, was highest in patients who had acute thrombus (81 +/- 19.7%), compared with subacute thrombus (61 +/- 22.5%) and complex cases involving acute and/or subacute thrombus on chronic scar (56 +/ 26.5%). VCSS scoring showed the number of patients with none and/or mild pain, varicose veins, and skin changes at 1-month remained stable at 12 months whereas the percent of patients with none and/or mild venous edema improved from 71.7% at 1 month (38 of 53) to 86.8% (46 of 53) at 12 months. Twenty-four-month follow-up data were available for only 15% (23 of 151) of patients. No clinically significant pulmonary emboli or major periprocedural bleeding events were reported. CONCLUSIONS: Patients with acute lower-extremity DVT involving the proximal veins can be safely and successfully treated with IPMTD. Major procedural bleeding was absent. The occurrence of severe PTS after primary treatment with Trellis-8 system IPMTD is low. Further long-term follow-up data are needed to confirm the benefit of intervention for thrombus removal compared with standard medical management. PMID- 26256711 TI - Endovascular Aneurysm Repair of Acute Occlusion of Abdominal Aortic Aneurysm with Intra-Aneurysmal Dissection. AB - BACKGROUND: To report a rare case of acute abdominal aortic aneurysm (AAA) occlusion successfully treated by endovascular aneurysm repair (EVAR). CASE REPORT: An 89-year-old man complained of severe back pain and weakness in the bilateral lower extremities. Although there were neither acute ischemic signs on the brain computed tomography (CT) nor critical leg ischemia, the patient presented progressing weakness in the bilateral lower extremities and decreased sensation in the perianal and saddle area. Contrast-enhanced CT demonstrated an infrarenal AAA, the formation of an ulcer-like lesion in the aneurysmal wall, and the complete occlusion of distal AAA because of the caudal extension of intramural hematoma. Both common iliac arteries were patent because of the development of collateral vessels. The neurologic symptoms were considered to be caused by the occlusion of lumbar radicular arteries. EVAR seemed anatomically feasible, if the occlusion could be crossed by guidewires from both side of the common femoral artery. Wires easily traversed the occlusion, and the stent graft could be smoothly unwrapped and opened. The patient could recover decent iliac arterial flow. The neurovascular deficits recovered within 4 days after the procedure. CONCLUSIONS: Although our experience may not be reproduced in all case of AAA occlusion, EVAR warrants consideration to reduce the high mortality rate associated with the classical treatments. PMID- 26256712 TI - Bilateral Axillary Artery Aneurysms Presenting as Upper Limb Ischemia. AB - An axillary artery aneurysm (AxAA) is a rare entity. Although some cases with AxAA are asymptomatic, complications including local pain, neurogenic symptoms, upper limb ischemia, and rupture may occur. Therefore, an early diagnosis and treatment are necessary. We herein report a case of bilateral AxAAs, in which the right AxAA showed acute upper limb ischemia and the left AxAA were asymptomatic. Both AxAAs were successfully treated by aneurysmectomy and interposition grafting. In the endovascular era, open surgical treatment for AxAAs remains a promising procedure. PMID- 26256713 TI - Inadvertent Arterial Placement of Central Venous Catheters: Diagnostic and Therapeutic Strategies. AB - BACKGROUND: Central venous catheterization (CVC) is among the most ubiquitous medical procedures. Inadvertent arterial placement of the catheter presents a challenging dilemma to the interventionalist. Treatment options include: removal and manual compression, off-label use of percutaneous closure devices and/or stent grafts, and open surgical removal. Potential sequelae include bleeding, thrombosis, stroke, limb ischemia, neurologic deficit, and death. Our aim is to evaluate the use of open and endovascular techniques for the management of iatrogenic carotid, subclavian, and brachiocephalic arterial injuries related to inadvertent arterial CVC placement. METHODS: Retrospective chart review revealed 13 patients with iatrogenic arterial injuries related to inadvertent arterial CVC placement over a 5-year period at Northwestern Memorial Hospital using Current Procedural Terminology codes and interventional radiology and vascular databases. Presenting features, radiographic diagnosis, therapeutic maneuvers, and outcomes were reviewed. RESULTS: Endovascular therapy was instituted in 10 cases with 3 requiring an adjunctive open procedure. In the endovascular therapy group, stent grafts were used in 5 patients and 4 patients were managed with percutaneous closure devices. In 1 patient, multiple embolization procedures were performed in an attempt to close a large innominate artery arteriovenous fistula (AVFs) that ultimately required sternotomy and surgical ligation for complete closure. Primary open repair was carried out in 3 patients. Two patients developed embolic stroke before therapy and removal, with 1 death reported at 36-month follow-up. Overall success rate with a single intervention was 100% (4 of 4) with closure devices, 80% (4 of 5) covered stents, 0% (0 of 1) with embolization, and 100% (3 of 3) with open intervention. Overall complication rate was 7% (1 of 13) requiring further open, invasive intervention. CONCLUSIONS: Management of carotid, subclavian, and brachiocephalic arterial injuries from attempted jugular or subclavian venous cannulation can be challenging. The risk of embolic phenomenon associated with arterial catheterization, and the noncompressible anatomic location at the base of the neck frequently prevent simple removal. We use a strategy of immediate computed tomography or magnetic resonance to facilitate the most appropriate therapy. Endovascular treatment with covered stent grants, percutaneous closure devices, and embolization offer good results when selected appropriately based on imaging evaluation. However, more complex cases with associated pseudoaneurysms and/or AVFs with larger catheters may require definitive open repair. PMID- 26256714 TI - A Systematic Review of Fenestrated Endovascular Repair for Juxtarenal and Short Neck Aortic Aneurysm: Evidence So Far. AB - BACKGROUND: Fenestrated endovascular repair is an alternative to open repair in the management of juxtarenal aortic aneurysms and short-neck abdominal aortic aneurysms (AAAs). The aim of this article is to examine the evidence in published literature on the use of fenestrated endovascular stent grafts in the treatment of juxtarenal and short-neck AAAs. METHODS: Systematic review was formulated under the instruction of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Articles published from January 1996 to October 2014 in English language were included. Published studies on fenestrated endovascular stent grafts in treating juxtarenal and short-neck AAAs were systematically searched and reviewed through a computerized search of PubMed and Ovid MEDLINE and cross-referenced. Title key words include "fenestrated", "juxtarenal", and "short neck". All relevant published articles up to first October 2014 were reviewed. RESULTS: A total of 529 nonduplicated publications were identified but only 15 articles were eligible for our qualitative analysis, with 763 patients and 2,040 target vessels. Twelve studies were included in cohort studies with a short or medium follow-up period (median range, 6-67 months). The mean 30-day and late follow-up mortality were 1.7% (range, 0-4%) and 20.1% (range, 4-50%), respectively, with 5.3% aneurysm-related late deaths. A total of 74 target vessels (3.6%) were lost in all the studies with 65 of them (87.8%) lost postoperatively. Overall, 28.8% patients endured renal dysfunction postoperatively, whereas 2.5% of patients required dialysis. Target vessel events and endoleaks were the 2 major indications for reintervention, accounting for 63.8%. Fourteen aneurysm sacs (1.8%) were enlarged continuously during follow-up and a half were due to type II endoleaks. Migration of the proximal fenestration component was reported with 3.0%. One registry study reported 4.1% of early mortality, higher than any cohort studies, whereas the target vessel loss was relatively low (1.6%). Freedom of late secondary intervention decreased from 90% at year 1 to 70% at year 3. Two nonrandom controlled comparative studies showed no definitive superiority of fenestrated repair over the open surgery. CONCLUSIONS: Contemporary published literature does not produce a high enough level of evidence that leads to a change in treatment guidelines for juxtarenal or short-neck aneurysm. Fenestrated endovascular repair is a safe and efficacious treatment, particularly for those deemed surgically high risk. Growing experience and innovation of stent graft are essential for the advancement of fenestrated grafting. PMID- 26256715 TI - Timing of Intervention in Blunt Traumatic Aortic Injury Patients: Open Surgical versus Endovascular Repair. AB - BACKGROUND: Thoracic endovascular aortic repair (TEVAR) is a rapidly evolving therapy in treating blunt traumatic aortic injury (TAI). However, currently there is no consensus among literature regarding the repair timing of TAI. Our experiences to manage TAI with comparison between open surgical and endovascular repair in repair timing and short-term outcomes are reported. Risk factors for postoperative mortality and morbidity are stratified. METHODS: Between January 2003 and February 2014, 63 consecutive patients who have suffered from TAI and underwent conventional open surgical or endovascular aortic repair were retrospectively reviewed in this study. The primary outcomes were in-hospital mortality, postoperative complication, and operation timing. All medical records regarding trauma mechanisms, concomitant injuries, intervention detail, and postoperative outcomes were reviewed and analyzed. RESULTS: Among the 63 patients (mean age, 37.9 years; 57 male), 23 underwent open repair (OR) and 40 underwent TEVAR for blunt TAI. The TEVAR group had more urgent operation (injury to repair <24 hr; 57.5% vs. 30.4%, P = 0.038) and shorter operative time (136.25 +/- 54.48 min vs. 414.78 +/- 212.24 min, P = 0.00) than the respective open surgical repair group. Postoperative mortality and morbidity analysis showed that the OR group had higher in-hospital mortality (30.4% vs. 7.5%; P = 0.029), more patients with acute renal failure in need of hemodialysis (17.4% vs. 2.3%; P = 0.038), and more post-operation infection (30.4% vs. 5%; P = 0.005) than the respective TEVAR group. The Multivariate analysis, of the 10 (15.88%) patients that died after the surgery, showed that the risk factors of hospital mortality were grade IV TAI (frank rupture). CONCLUSIONS: For treating TAI, TEVAR has emerged as a quicker and safer treatment option than OR. The findings of this study support the use of TEVAR over OR for patients who suffered from TAI. PMID- 26256716 TI - Osmotolerance provided by the alternative sigma factors sigmaB and rpoS to Staphylococcus aureus and Escherichia coli is solute dependent and does not result in an increased growth fitness in NaCl containing media. AB - The aim of this work was to examine the role of the alternative general stress sigma factors sigma(B) and rpoS on the ability of Staphylococcus aureus and Escherichia coli, respectively, to grow in liquid and solid media of different osmolarity. For this purpose, S. aureus strain Newman and its isogenic DeltasigB mutant IK84 and E. coli strain BJ4 and its isogenic DeltarpoS mutant BJ4L1 were grown in media (TSBYE) with different concentrations of NaCl. Growth parameters (lag phase duration, growth rate and maximum number of microorganisms) and limiting growth concentrations (Maximum Non-Inhibitory Concentration - MNIC - and Minimum Inhibitory Concentration - MIC-) were determined. The mechanisms underlying the differences observed between parental and mutant strains were also explored. The absence of the sigma factors sigma(B) and rpoS led to a decrease in the MNICs and MICs calculated for S. aureus and E. coli, respectively. Conversely, neither sigma(B) nor rpoS provided with increased growth fitness to S. aureus and E. coli cells at NaCl concentrations up to 1.36M and 1M, respectively. The decreased osmotolerance of the sigma(B) and rpoS deficient strains, as compared to their parental strains, was compensated by the addition of glycine-betaine (1mM) to the growth medium. It was also observed that the decreased tolerance to NaCl of the mutant strains was coincident with a decreased tolerance to sucrose, KCl, and LiCl but not to glycerol, MgCl2, and CaCl2. Results obtained also demonstrate that the increased osmotolerance of stationary growth phase E. coli cells, as compared to exponential growth phase ones, would be due to the activation of both rpoS-independent and rpoS-dependent mechanisms. This work will help to understand the mechanisms of bacterial resistance to osmotic stress and the role of the alternative sigma factors sigma(B) and rpoS in this process. PMID- 26256717 TI - Exopolysaccharides from co-cultures of Weissella confusa 11GU-1 and Propionibacterium freudenreichii JS15 act synergistically on wheat dough and bread texture. AB - The storage of bread is limited by both physical (staling) and microbial (mainly fungal) spoilage. Exopolysaccharides (EPS) produced by lactic acid bacteria (LAB) and organic acids from propionibacteria (PAB) have been used to enhance texture and extend shelf-life of bakery products. In this study the functionality of EPS of Weissella confusa A3/2-1 (dextran), W. confusa F3/2-2 (dextran and levan), W. confusa 11GU-1 (dextran and ropy capsular polysaccharide) was evaluated in wheat bread. Two strains of Propionibacterium freudenreichii (Pf), shown to produce a heteropolysaccharide (Pf JS15) or a beta-glucan (Pf DF30), were tested in single and mixed cultures with W. confusa (Wc). The EPS fermentates were prepared by batch fermentation of cereal- or malt-based medium using sucrose (Wc) or lactic acid (Pf) as carbon source. Incorporation of EPS from single culture fermentates and 1:1 Weissella-Propionibacterium fermentate mixtures revealed strong positive effects of dextran and ropy capsular polysaccharide produced by Wc 11GU-1 on bread staling retardation, with synergistic effects of EPS mixture from Wc 11GU-1 and Pf JS15. A co-fermentation of Wc 11GU-1 and Pf JS15 was developed to produce EPS together with antifungal organic acid mixture (acetate and propionate) in a single step process. The addition of 15% (w/w flour base) co-culture, yielding EPS, acetate and propionate concentrations of 1.5, 0.5 and 1g/kg dough, respectively, resulted in improved bread texture, increased loaf volume and decreased crumb firming during storage for 3days compared with control breads and breads supplemented with equivalent levels of chemical organic acids. Our data showed that EPS could compensate for the negative effects of chemical acetate and propionate in a concentration range exerting antifungal effects. The natural bioingredient produced by Wc 11GU-1 and Pf JS15 has potential for applications as antifungal, texture-building and anti-staling agent in breads, consistent with consumer demands for clean label products. PMID- 26256718 TI - Clustered array of ochratoxin A biosynthetic genes in Aspergillus steynii and their expression patterns in permissive conditions. AB - Aspergillus steynii is probably the most relevant species of section Circumdati producing ochratoxin A (OTA). This mycotoxin contaminates a wide number of commodities and it is highly toxic for humans and animals. Little is known on the biosynthetic genes and their regulation in Aspergillus species. In this work, we identified and analysed three contiguous genes in A. steynii using 5'-RACE and genome walking approaches which predicted a cytochrome P450 monooxygenase (p450ste), a non-ribosomal peptide synthetase (nrpsste) and a polyketide synthase (pksste). These three genes were contiguous within a 20742 bp long genomic DNA fragment. Their corresponding cDNA were sequenced and their expression was analysed in three A. steynii strains using real time RT-PCR specific assays in permissive conditions in in vitro cultures. OTA was also analysed in these cultures. Comparative analyses of predicted genomic, cDNA and amino acid sequences were performed with sequences of similar gene functions. All the results obtained in these analyses were consistent and point out the involvement of these three genes in OTA biosynthesis by A. steynii and showed a co-ordinated expression pattern. This is the first time that a clustered organization OTA biosynthetic genes has been reported in Aspergillus genus. The results also suggested that this situation might be common in Aspergillus OTA-producing species and distinct to the one described for Penicillium species. PMID- 26256719 TI - Controlling the "uncontrollable": Faking effects on the affect misattribution procedure. AB - In two experiments, the impact of faking on the affect misattribution procedure (AMP) was examined. Results revealed that faking influences both the overall means and the convergent validity of AMP effects in terms of correlations with self-report measures. Faking effects were very selective in that they affected fake-prime trials only, for which AMP effects were significant, but reversed in direction, while AMP effects for non-fake trials remained intact. Importantly, neither strategic advice nor prior task experience was a necessary prerequisite for successful faking. The discussion focuses on possible processes underlying successful faking in the AMP. PMID- 26256720 TI - Cerebral oxygenation in the beach chair position before and during general anesthesia in patients with and without cardiovascular risk factors. AB - STUDY OBJECTIVES: To evaluate changes in cerebral tissue oxygen index (TOI) values under the beach chair position before and during general anesthesia in surgical patients with or without cardiovascular risk factors. DESIGN: Prospective study. SETTING: Operating room in the university hospital. PATIENTS: Ninety-one patients undergoing surgery, including healthy patients (n = 28), patients with 1 cardiovascular risk factor (n = 33), and those with more than 1 risk factor (n = 30). INTERVENTIONS AND MEASUREMENTS: Cerebral TOI the day before and during general anesthesia was evaluated using a near-infrared spectroscopy NIRO-200 (Hamamatsu Photonics, Hamamatsu, Japan) for each patient. The initial TOI measurement in the supine position after a 10-minute rest or 10 minute after the endotracheal intubation was followed by measurements in 30 degrees and subsequent 60 degrees upright position for 5 minutes. Phenylephrine 0.1 mg and/or ephedrine 4 mg was administered intravenously to maintain mean blood pressure above 60 mm Hg accordingly. MAIN RESULTS: The beach chair position decreased mean arterial blood pressure and heart rate under general anesthesia, although patients with more than 1 cardiovascular risk factor needed significantly more phenylephrine doses to maintain mean blood pressure above 60 mm Hg. Values of TOI were within the normal range of about 70% before and during anesthesia in all groups. CONCLUSIONS: The beach chair position under general anesthesia did not alter cerebral oxygenation in patients with or without cardiovascular risk factors showing normal preoperative cerebral TOI values when the mean blood pressure was maintained above 60 mm Hg. The careful management using the cerebral oxygenation monitoring appears to maintain cerebral perfusion in the beach chair position during general anesthesia. PMID- 26256721 TI - Removal of an epidural catheter without discontinuation of dual antiplatelet therapy in a patient with postoperative urgent coronary stenting. PMID- 26256722 TI - VIA score: a mnemonic for airway assessment and management. PMID- 26256723 TI - Air-Q intubating supraglottic device for tracheal tumor resection. PMID- 26256724 TI - Erratum to: Mental Health and Its Associated Variables Among International Students at a Japanese University: With Special Reference to Their Financial Status. PMID- 26256725 TI - Correction: Eczema therapeutics in children: what do the clinical trials say? PMID- 26256726 TI - The Human Y-Chromosome - Introduction into Genetics and Applications. AB - Human Y-chromosomal DNA analysis is becoming well established in forensic sciences. That is because human Y-chromosomal DNA polymorphisms are the only genetic markers that are able to specifically characterize and identify male culprit DNA in material from sexual assault or forcible rape cases where offenders are almost always males. Appropriate Y-chromosomal DNA markers evaluated for forensic applications with standardized nomenclature, typing and statistic methodology, and haplotype frequency databases are currently available to the forensic DNA community. As with any other kind of DNA evidence, the Y chromosomal DNA analysis in forensic science requires not only a high standard of quality assurance but also appropriate scientific background knowledge to ensure correct interpretation of DNA profiles. The following overview article will provide an introduction to the molecular genetics of the human Y-chromosome and will discuss the advantages that Y-chromosomal DNA polymorphisms can offer to forensic applications, as well as the limitations to the types of information provided by the human Y-chromosome. PMID- 26256727 TI - Recent Developments in Y-Short Tandem Repeat and Y-Single Nucleotide Polymorphism Analysis. AB - This article reviews new genetic markers on the Y-chromosome and methods for analyzing these short tandem repeat (STR) and single nucleotide polymorphism (SNP) loci. Relative chromosomal locations for over 50 Y-chromosome STRs (Y-STRs) are described along with their repeat motif and allele range characteristics based on published population studies. Multiplex assays for typing many of these markers in a parallel fashion are discussed, as are newly available commercial Y STR kits. Approximately 250 SNP markers are now catalogued along the Y-chromosome (Y-SNPs) with a unified haplogroup nomenclature describing their relative relationships. Technologies for typing these Y-SNPs are reviewed including primer extension and allele-specific hybridization methods. Finally, available reference materials for standardization of allele calls, Y-STR allele nomenclature issues, and published validation and interlaboratory studies are reviewed. PMID- 26256728 TI - Y-Short Tandem Repeat Multiplex Systems - Y-PLEXTM 6 and Y-PLEXTM 5. AB - Y-Chromosome short tandem repeats (Y-STRs) have become a very useful tool in forensic casework, paternity, and male lineage studies. In forensic casework, one can obtain the male profile from a mixture sample containing male and female DNA. Two Y-STR genotyping systems, Y-PLEXTM 6 and Y-PLEXTM 5, have been developed for use in human identification. Y-PLEXTM 6 enables simultaneous amplification of DYS393, DYS19, DYS389II, DYS390, DYS391, and DYS385; Y-PLEXTM 5 enables simultaneous amplification of DYS389I, DYS389II, DYS439, DYS438, and DYS392 loci. The Y-PLEXTM 6 and Y-PLEXTM 5 systems together provide analysis of all nine Y-STR loci generating minimal haplotype and two additional loci, DYS438 and DYS439. These systems also provide analysis for all 11 Y-STR loci recommended by the Scientific Working Group on DNA Analysis Methods (SWGDAM) for forensic casework and population database studies. Both the systems were validated following the Federal Bureau of Investigation (FBI) Director's Quality Assurance Standards. Allelic ladders, which serve as a reference in genotyping, were generated. The nucleotide sequence of alleles in the allelic ladder was determined and the nomenclature is in accord with the recommendations of the International Society of Forensic Genetics (ISFG). The minimum sensitivity of the Y-PLEXTM 6 and Y PLEXTM 5 systems was 0.2 and 0.1 ng of male DNA, respectively. The nonhuman study revealed that the primers in the Y-PLEXTM 6 and Y-PLEXTM 5 systems were specific for the DNA from humans and some higher primates. Mean stutter values ranged from 3.6 to 11.9%. The Y-PLEXTM 6 and Y-PLEXTM 5 systems were used in several forensic cases. The results from these multiplex systems have been admitted in various U.S. Courts. Thus, Y-PLEXTM 6 and Y-PLEXTM 5 genotyping systems are sensitive, reliable, and robust for use in human forensic and male lineage identification studies. PMID- 26256729 TI - Strategies for the Design and Assessment of Y-Short Tandem Repeat Multiplexes for Forensic Use. AB - In order to improve the discriminatory potential, and hence the probative value, of Y-STR-based testing, the set of Y-chromosome STR loci available for forensic use needs to be expanded. We have designed and tested two novel Y-STR multiplexes for potential forensic casework use. In accord with the requirements of Y chromosome multiplex analytical systems developed specifically for forensic casework use, we have tried to maximize the number of loci able to be co amplified and minimize confounding female DNA artifacts while ensuring appropriate assay sensitivity (1-2 ng of input genomic DNA) and interlocus signal balance. This review will describe the strategies that we have developed that may provide guidance for the design and assessment of novel Y-STR multiplex systems. Novel Y-STR multiplexes developed for forensic use need to undergo a series of validation exercises that go beyond simply optimizing the PCR reaction conditions. Specifically, stringent performance checks on their efficacy need to be carried out using casework type specimens in order to determine potential confounding effects from female DNA. PMID- 26256730 TI - Utility of Y-Chromosome Short Tandem Repeat Haplotypes in Forensic Applications. AB - Patrilineally transmitted Y-chromosomal markers have been shown to resolve forensic cases under certain scenarios where autosomal markers provide limited or inconclusive evidence. Several Y-short tandem repeat (Y-STR) loci have been validated for forensic use, and Y-STR haplotype databases for a number of geographic locations are now available in the literature and online. In this review, examples are presented of situations where Y-STR loci can provide valuable supplemental forensic evidence when autosomal STR loci fail or provide little evidence. Also, different methods of interpreting Y-STR forensic evidence in casework analysis are outlined, suggesting that in spite of excessive conservativeness, the counting method is still the most simple and easily defensible method of interpreting Y-STR forensic evidence. While the need for developing more powerful interpretation methods should be considered, it is stressed that expansion of Y-STR databases should focus on increasing sample sizes and the inclusion of more anthropologically defined populations to improve the efficiency of interpretation of Y-STR markers in forensic applications. PMID- 26256731 TI - The Y-Short Tandem Repeat Haplotype Reference Database (YHRD) and Male Population Stratification in Europe - Impact on Forensic Genetics. AB - The forensic application of patrilinearly transmitted Y-chromosomal markers requires knowledge of its substantial sensitivity to population substructuring. The establishment of carefully constructed, large, onlineavailable and worldwide population databases for Y-short tandem repeat-based haplotypes illustrates the magnitude and importance of male population subdivision, which is even recognizable in the otherwise nearly indistinguishable European populations. Thus, the choice of the suitable reference population is an absolute requirement for the interpretation of haplotype matches. Based on the specific haplotype distribution in a given population, an extrapolation method has been worked out that allows the frequency estimation of very rare haplotypes. This "haplotype surveying" approach is recommended as a conservative method to assess the match probabilities in cases with non-exclusion constellations. As exemplified further, the population-specific distribution of haplotypes can help to infer the population of origin of an unknown male DNA. PMID- 26256732 TI - Population Database and Mutation Study for Short Tandem Repeat Loci on Y Chromosome (Y-STRs) in Japanese Populations. AB - A database for 14 short tandem repeat loci on Y-chromosome (Y-STRs) (DYS393, DYS19, DYS391, DYS437, DYS435, DYS439, DYS389II, DYS438, DYS436, DYS390, Y-GATA H4, DYS385, DYS460, and DYS392) was constructed from 207 Honshu-Japanese (main island of Japan, Nagoya City) and 87 Okinawa-Japanese (southernmost islands of Japan) male DNA specimens. The samples were analyzed for 14 Y-STRs using two multiplex PCR typing systems, a newly devised 10-plex amplification system, and a commercially available Y-PLEXTM 6. The allele frequencies at 14 loci were calculated in each population and the distributions between both populations were significantly different at four of the 14 loci. A total of 244 unique haplotypes were observed in both Japanese populations, and 17 haplotypes were observed more than once. The two populations shared only seven haplotypes. The haplotype diversities for tested loci were 0.9987 and 0.9976 in Honshu- and Okinawa Japanese, respectively. In the 10-plex, however, an extremely uninformative trinucleotide-repeat DYS436 was replaced with a more informative tetranucleotide repeat locus, DYS389I, with a newly designed primer set to evolve modified 10 plex. With the modified 10-plex, since the number of unique haplotypes increased each one in both populations, the haplotype diversity values increased to 0.9988 and 0.9979 in Honshu- and Okinawa-Japanese, respectively. At present, in terms of the numbers of loci and individuals profiled, this database is the most informative in Japan. Only one instance of mutation was observed among the 51 Japanese father-son samples tested for the modified 14 loci Haplotype analysis at 14 Y-STR loci, especially at the modified 14 Y-STR loci, would be more useful in forensic fields and in population genetics. PMID- 26256733 TI - Forensic Applications of Y-Short Tandem Repeats. AB - Y-short tandem repeats (STRs) are located in the nonrecombining part of the Y chromosome. Its genetic characteristics are helpful to paternity testing. The male lineage can be pursued over several generations. Since an overwhelming majority of rape or sexual assault cases involve male suspects, these markers proved to be very useful with mixed stains. Routine casework performed in our laboratory has demonstrated that Y-STRs analysis can detect minimal amounts of male DNA in a stain. Analysis of Y-STRs should be conducted even when preliminary tests for the presence of sperms are negative or when the analysis of autosomal STRs shows no male component in the mixed stains. PMID- 26256734 TI - Advantages and Disadvantages of Y-Short Tandem Repeat Testing in Forensic Casework. AB - Y-chromosome-specific human DNA markers can be a useful tool in forensic casework. Several case scenarios are presented to point out the advantages and disadvantages of Y-STR testing over autosomal STR testing. The main advantage of the Y-STR approach is the ability to detect the male component even in extreme mixtures of male and female DNA. It is also useful for rapid screening of large number of stains and the determination of the number of semen donors for mixtures of two or more male individuals. The main disadvantage is the inability to distinguish between male relatives and the limitations of the haplotype frequency approach. PMID- 26256735 TI - Forensic Casework Applications Using Y-PLEXTM 6 and Y-PLEXTM 5 Systems. AB - Analysis for Y-chromosome short tandem repeat (Y-STR) loci has become a useful tool in resolving difficult cases, particularly with evidence samples containing mixtures of male and female DNA. The Y-PLEXTM 6 and Y-PLEXTM 5 systems have been validated and used in forensic cases. A total of 188 samples, which included 127 evidence samples, have been analyzed using Y-PLEXTM 6 and Y-PLEXTM 5 systems. The evidence sample types included fingernails, sperm, epithelial cells, blood, and tissue. The results from five cases are discussed. The results from Y-PLEXTM 6 kits have accepted in several jurisdictions throughout the United States. PMID- 26256736 TI - Are older adults living in more equal counties healthier than older adults living in more unequal counties? A propensity score matching approach. AB - We assessed the potential contextual effect of income inequality on health by: 1) comparing individuals with similar socioeconomic status (SES) but who reside in counties with different levels of income inequality; and 2) examining whether the potential effect of county-level income inequality on health varies across SES groups. We used the Health and Retirement Study, a nationally representative study of Americans over the age of 50. Using propensity score matching, we selected SES-comparable individuals living in high-income inequality counties and in low-income inequality counties. We examined differences in self-rated overall health outcomes and in other specific physical/mental health outcomes between the two groups using logistic regression (n = 34,994) and imposing different sample restrictions based on residential duration in the area. We then used logistic regression with interactions to assess whether, and if so how, health outcomes differed among participants of different SES groups defined by wealth, income, and education. In bivariate analyses of the unmatched full sample, adults living in high-income inequality counties have worse health outcomes for most health measures. After propensity score matching, adults in high-income inequality counties had worse self-rated health status (AOR = 1.12; 95% CI 1.04-1.19) and were more likely to report diagnosed psychiatric problems (AOR = 1.08; 95% CI 0.99-1.19) than their matched counterparts in low-income inequality counties. These associations were stronger with longer-term residents in the area. Adverse health outcomes associated with living in high-income inequality counties were significant particularly for individuals in the 30(th) or greater percentiles of income/wealth distribution and those without a college education. In summary, after using more precise matching methods to compare individuals with similar characteristics and addressing measurement error by excluding more recently arrived county residents, adults living in high-income inequality counties had worse reported overall physical and mental health than adults living in low income inequality counties. PMID- 26256738 TI - Remote cerebellar haemorrhage from site of craniotomy: A report of two cases. AB - Remote cerebellar haemorrhage (RCH) is a rare complication of neurosurgical procedures seldom requiring intervention. We report two cases of RCH. The first unilateral RCH is asymptomatic, the other is bilateral and associated with supratentorial haemorrhage and hydrocephalus requiring intervention. We propose multiple foci of haemorrhage as an adverse prognostic marker in RCH. PMID- 26256737 TI - Automated compromised right lung segmentation method using a robust atlas-based active volume model with sparse shape composition prior in CT. AB - To resolve challenges in image segmentation in oncologic patients with severely compromised lung, we propose an automated right lung segmentation framework that uses a robust, atlas-based active volume model with a sparse shape composition prior. The robust atlas is achieved by combining the atlas with the output of sparse shape composition. Thoracic computed tomography images (n=38) from patients with lung tumors were collected. The right lung in each scan was manually segmented to build a reference training dataset against which the performance of the automated segmentation method was assessed. The quantitative results of this proposed segmentation method with sparse shape composition achieved mean Dice similarity coefficient (DSC) of (0.72, 0.81) with 95% CI, mean accuracy (ACC) of (0.97, 0.98) with 95% CI, and mean relative error (RE) of (0.46, 0.74) with 95% CI. Both qualitative and quantitative comparisons suggest that this proposed method can achieve better segmentation accuracy with less variance than other atlas-based segmentation methods in the compromised lung segmentation. PMID- 26256739 TI - Classical imaging findings in spinal subdural hematoma - "Mercedes-Benz" and "Cap" signs. PMID- 26256741 TI - [The peritoneum is a full specific organ, requiring specific pathological exams]. PMID- 26256740 TI - Fibrinogen production is enhanced in an in-vitro model of non-alcoholic fatty liver disease: an isolated risk factor for cardiovascular events? AB - BACKGROUND: Cardiovascular disease (CVD) remains the major cause of excess mortality in patients with non-alcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the individual contribution of NAFLD to CVD risk factors in the absence of pathogenic influences from other comorbidities often found in NAFLD patients, by using an established in-vitro model of hepatic steatosis. METHODS: Histopathological events in non-alcoholic fatty liver disease were recapitulated by focused metabolic nutrient overload of hepatoblastoma C3A cells, using oleate-treated-cells and untreated controls for comparison. Microarray and proteomic data from cell culture experiments were integrated into a custom-built systems biology database and proteogenomics analysis performed. Candidate genes with significant dysregulation and concomitant changes in protein abundance were identified and STRING association and enrichment analysis performed to identify putative pathogenic pathways. RESULTS: The search strategy yielded 3 candidate genes that were specifically and significantly up-regulated in nutrient-overloaded cells compared to untreated controls: fibrinogen alpha chain (2.2 fold), fibrinogen beta chain (2.3 fold) and fibrinogen gamma chain (2.1 fold) (all rank products pfp <0.05). Fibrinogen alpha and gamma chain also demonstrated significant concomitant increases in protein abundance (3.8-fold and 2.0-fold, respectively, p <0.05). CONCLUSIONS: In-vitro modelling of NAFLD and reactive oxygen species formation in nutrient overloaded C3A cells, in the absence of pathogenic influences from other comorbidities, suggests that NAFLD is an isolated determinant of CVD. Nutrient overload-induced up-regulation of all three fibrinogen component subunits of the coagulation cascade provides a possible mechanism to explain the excess CVD mortality observed in NAFLD patients. PMID- 26256742 TI - Interplay of medication errors and the separation of dispensing. PMID- 26256743 TI - [Side effects of anticancer treatment and the needs for translational research on toxicity: a clinician's perspective]. PMID- 26256744 TI - [A challenge to overcome stomatitis of cancer patients treated with chemotherapy]. PMID- 26256745 TI - [Establishment of new cancer cachexia rat model and evaluation of a promising medicine based on pathophysiology of this model - the mechanism by which rikkunshito ameliorates cancer cachexia]. PMID- 26256746 TI - [Pain relieving effect of platelet-activating factor (PAF) antagonists in a bone cancer pain model]. PMID- 26256747 TI - [New molecular basis in the regulation of lipolysis via dephosphorylation]. PMID- 26256748 TI - [From the connectome to brain function: rabies virus tools for elucidating structure and function of neural circuits]. PMID- 26256749 TI - [Pharmacological profile and clinical efficacy of human anti-human PD-1 antibody nivolumab (OPDIVO(r)) as a new immune checkpoint inhibitor]. PMID- 26256750 TI - [Role-play for pharmacology education: active learning through the Case & Communication based approach]. PMID- 26256751 TI - [Photoactivated adenylyl cyclase, a new optogenetic tool for neurobiology]. PMID- 26256752 TI - Vertical jumping biomechanical evaluation through the use of an inertial sensor based technology. AB - Progress in micro-electromechanical systems has turned inertial sensor units (IUs) into a suitable tool for vertical jumping evaluation. In total, 9 men and 8 women were recruited for this study. Three types of vertical jumping tests were evaluated in order to determine if the data provided by an IU placed at the lumbar spine could reliably assess jumping biomechanics and to examine the validity of the IU compared with force plate platform recordings. Robust correlation levels of the IU-based jumping biomechanical evaluation with respect to the force plate across the entire analysed jumping battery were found. In this sense, significant and extremely large correlations were found when raw data of both IU and force plate-derived normalised force-time curves were compared. Furthermore, significant and mainly moderate correlation levels were also found between both instruments when isolated resultant forces' peak values of predefined jumping phases of each manoeuvre were analysed. However, Bland and Altman graphical representation demonstrated a systematic error in the distribution of the data points within the mean +/-1.96 SD intervals. Using IUs, several biomechanical variables such as the resultant force-time curve patterns of the three different vertical jumps analysed were reliably measured. PMID- 26256753 TI - Accuracy and repeatability of an inertial measurement unit system for field-based occupational studies. AB - The accuracy and repeatability of an inertial measurement unit (IMU) system for directly measuring trunk angular displacement and upper arm elevation were evaluated over eight hours (i) in comparison to a gold standard, optical motion capture (OMC) system in a laboratory setting, and (ii) during a field-based assessment of dairy parlour work. Sample-to-sample root mean square differences between the IMU and OMC system ranged from 4.1 degrees to 6.6 degrees for the trunk and 7.2 degrees -12.1 degrees for the upper arm depending on the processing method. Estimates of mean angular displacement and angular displacement variation (difference between the 90th and 10th percentiles of angular displacement) were observed to change <4.5 degrees on average in the laboratory and <1.5 degrees on average in the field per eight hours of data collection. Results suggest the IMU system may serve as an acceptable instrument for directly measuring trunk and upper arm postures in field-based occupational exposure assessment studies with long sampling durations. Practitioner Summary: Few studies have evaluated inertial measurement unit (IMU) systems in the field or over long sampling durations. Results of this study indicate that the IMU system evaluated has reasonably good accuracy and repeatability for use in a field setting over a long sampling duration. PMID- 26256754 TI - Supramolecular Ga4L6(12-) Cage Photosensitizes 1,3-Rearrangement of Encapsulated Guest via Photoinduced Electron Transfer. AB - The K12Ga4L6 supramolecular cage is photoactive and enables an unprecedented photoreaction not observed in bulk solution. Ga4L6(12-) cages photosensitize the 1,3-rearrangement of encapsulated cinnamylammonium cation guests from the linear isomer to the higher energy branched isomer when irradiated with UVA light. The rearrangement requires light and guest encapsulation to occur. The Ga4L6(12-) cage-mediated reaction mechanism was investigated by UV/vis absorption, fluorescence, ultrafast transient absorption, and electrochemical experiments. The results support a photoinduced electron transfer mechanism for the 1,3 rearrangement, in which the Ga4L6(12-) cage absorbs photons and transfers an electron to the encapsulated cinnamylammonium ion, which undergoes C-N bond cleavage, followed by back electron transfer to the cage and recombination of the guest fragments to form the higher energy isomer. PMID- 26256755 TI - Characterization of Folic Acid and Poly(amidoamine) Dendrimer Interactions with Folate Binding Protein: A Force-Pulling Study. AB - Atomic force microscopy force-pulling experiments have been used to measure the binding forces between folic acid (FA) conjugated poly(amidoamine) (PAMAM) dendrimers and folate binding protein (FBP). The generation 5 (G5) PAMAM conjugates contained an average of 2.7, 4.7, and 7.2 FA per dendrimer. The most probable rupture force was measured to be 83, 201, and 189 pN for G5-FA2.7, G5 FA4.7, and G5-FA7.2, respectively. Folic acid blocking experiments for G5-FA7.2 reduced the frequency of successful binding events and increased the magnitude of the average rupture force to 274 pN. The force data are interpreted as arising from a network of van der Waals and electrostatic interactions that form between FBP and G5 PAMAM dendrimer, resulting in a binding strength far greater than that expected for an interaction between FA and FBP alone. PMID- 26256756 TI - Synthesis of oligodiaminomannoses and analysis of their RNA duplex binding properties and their potential application as siRNA-based drugs. AB - The synthesis of artificial cationic oligodiaminosaccharides, alpha-(1 -> 4) linked-2,6-diamino-2,6-dideoxy-d-mannopyranose oligomers (ODAMans), and their interactions with RNA duplexes are described. The monomer through the pentamer, all of which bear unnatural 2,6-diaminomannose moieties, were successfully prepared. UV melting and fluorescence anisotropy analyses revealed that the ODAMans bound and thermodynamically stabilized both 12mer RNA duplexes and an siRNA. Furthermore, it was clearly shown that the siRNA acquired substantial RNase A resistance due to its binding to the ODAMan 4mer. PMID- 26256758 TI - Online probing quantum dots and engineered enzyme self-assembly in a nanoliter scale. AB - Nanoparticles provide significantly enhanced binding characteristics. However, fast online probing of the self-assembly process remains hard to achieve in practice. Herein, we report a fluorescence coupled CE method for probing the self assembly events between quantum dots (QDs) and engineered Jumonji domain containing protein 6 (Jmjd6) enzyme. QDs and Jmjd6 were sequentially injected into the capillary, where the self-assembly took place in a nanoliter scale. In particular, we showed that the Jmjd6/QD ratio, the interval time, and the injection volume had a great effect on the online self-assembly. The current approach may allow for a better understanding of QDs-enzyme self-assembly and enzymatic activity detection. PMID- 26256759 TI - A novel clinicogenetic prognostic score for follicular lymphoma. PMID- 26256761 TI - Disparities in cancer mortality for elderly poor in the USA. PMID- 26256762 TI - Urine test can detect early stage pancreatic cancer. PMID- 26256760 TI - Integration of gene mutations in risk prognostication for patients receiving first-line immunochemotherapy for follicular lymphoma: a retrospective analysis of a prospective clinical trial and validation in a population-based registry. AB - BACKGROUND: Follicular lymphoma is a clinically and genetically heterogeneous disease, but the prognostic value of somatic mutations has not been systematically assessed. We aimed to improve risk stratification of patients receiving first-line immunochemotherapy by integrating gene mutations into a prognostic model. METHODS: We did DNA deep sequencing to retrospectively analyse the mutation status of 74 genes in 151 follicular lymphoma biopsy specimens that were obtained from patients within 1 year before beginning immunochemotherapy consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). These patients were recruited between May 4, 2000, and Oct 20, 2010, as part of a phase 3 trial (GLSG2000). Eligible patients had symptomatic, advanced stage follicular lymphoma and were previously untreated. The primary endpoints were failure-free survival (defined as less than a partial remission at the end of induction, relapse, progression, or death) and overall survival calculated from date of treatment initiation. Median follow-up was 7.7 years (IQR 5.5-9.3). Mutations and clinical factors were incorporated into a risk model for failure-free survival using multivariable L1-penalised Cox regression. We validated the risk model in an independent population-based cohort of 107 patients with symptomatic follicular lymphoma considered ineligible for curative irradiation. Pretreatment biopsies were taken between Feb 24, 2004, and Nov 24, 2009, within 1 year before beginning first-line immunochemotherapy consisting of rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP). Median follow up was 6.7 years (IQR 5.7-7.6). FINDINGS: We established a clinicogenetic risk model (termed m7-FLIPI) that included the mutation status of seven genes (EZH2, ARID1A, MEF2B, EP300, FOXO1, CREBBP, and CARD11), the Follicular Lymphoma International Prognostic Index (FLIPI), and Eastern Cooperative Oncology Group (ECOG) performance status. In the training cohort, m7-FLIPI defined a high-risk group (28%, 43/151) with 5-year failure-free survival of 38.29% (95% CI 25.31 57.95) versus 77.21% (95% CI 69.21-86.14) for the low-risk group (hazard ratio [HR] 4.14, 95% CI 2.47-6.93; p<0.0001; bootstrap-corrected HR 2.02), and outperformed a prognostic model of only gene mutations (HR 3.76, 95% CI 2.10 6.74; p<0.0001; bootstrap-corrected HR 1.57). The positive predictive value and negative predictive value for 5-year failure-free survival were 64% and 78%, respectively, with a C-index of 0.80 (95% CI 0.71-0.89). In the validation cohort, m7-FLIPI again defined a high-risk group (22%, 24/107) with 5-year failure-free survival of 25.00% (95% CI 12.50-49.99) versus 68.24% (58.84-79.15) in the low-risk group (HR 3.58, 95% CI 2.00-6.42; p<0.0001). The positive predictive value for 5-year failure-free survival was 72% and 68% for negative predictive value, with a C-index of 0.79 (95% CI 0.69-0.89). In the validation cohort, risk stratification by m7-FLIPI outperformed FLIPI alone (HR 2.18, 95% CI 1.21-3.92), and FLIPI combined with ECOG performance status (HR 2.03, 95% CI 1.12 3.67). INTERPRETATION: Integration of the mutational status of seven genes with clinical risk factors improves prognostication for patients with follicular lymphoma receiving first-line immunochemotherapy and is a promising approach to identify the subset at highest risk of treatment failure. FUNDING: Deutsche Krebshilfe, Terry Fox Research Institute. PMID- 26256763 TI - Physiological concentrations of albumin favor drug binding. AB - The ability to track drug binding and release makes electron paramagnetic resonance (EPR) spectroscopy well suited for drug delivery studies. Using the continuous wave (cw) EPR technique to extract information about the dynamics of the spin labeled drugs we can simultaneously determine the bound and unbound drugs. Here, spin labeled salicylic acid (SLSA) binding to and release from bovine serum albumin (BSA) is investigated, as a model for drug-transport protein interaction. We studied SLSA-BSA binding in a wide concentration range and found that the stoichiometry of the drug-protein increases significantly when the physiological range of BSA concentration is reached. Our EPR results explicitly reveal that up to ~7 SLSA can bind to one albumin at the physiological concentration, whereas at lower BSA concentrations (<0.125 mM) the SLSA-BSA stoichiometry is maximum 2. Moreover, we studied drug release and showed that the ratio of bound to unbound SLSA concentrations remains relatively stable during dialysis. This indicates that the binding equilibrium of SLSA is not altered through the process of dialysis. This study demonstrates that cw EPR spectroscopy in combination with spin labeled drugs is an effective technique for binding and release studies and stoichiometric analysis of drug-protein interactions. PMID- 26256765 TI - Accumulation and effects of sediment-associated silver nanoparticles to sediment dwelling invertebrates. AB - Sediment is increasingly recognized as the major sink for contaminants including nanoparticles (NPs). Thus, sediment-living organisms are especially susceptible to NP exposure. Studies of the fate and effects of NPs in the sediment matrix are still in their infancy, and data from such studies are in high demand. Here, we examine the effects of exposure to sediment mixed with either aqueous Ag (administered as AgNO3) or Ag NPs (13nm, citrate-capped) at a nominal exposure concentration of 100MUg Ag/g dry weight sediment on four benthic invertebrates: two clones of the gastropod Potamopyrgus antipodarum (clones A and B) and two polychaete species (Capitella teleta, Capitella sp. S). Our results show that both species sensitivity and Ag form (aqueous Ag, Ag NPs) play a role in bioaccumulation and effects. Following two weeks of exposure, both clones of P. antipodarum were found to be insensitive towards both Ag forms (generally low Ag accumulation, no toxicity). In contrast, the two Capitella species varied widely with respect to Ag uptake and observed toxicity. Capitella sp. S was adversely affected by both aqueous Ag (mortality) and Ag NPs (growth), whereas C. teleta was not affected by either Ag form. For neither polychaete species was the observed toxicity directly related to bioaccumulation. Therefore, future nano ecotoxicological research should focus on understanding differences in uptake and handling mechanisms among species and the relationship between bioaccumulation and toxicity. PMID- 26256764 TI - Paclitaxel-induced lung injury and its amelioration by parecoxib sodium. AB - To investigate the mechanism of paclitaxel-induced lung injury and its amelioration by parecoxib sodium. In this study, rats were randomly divided into: the control group (Con); the paclitaxel chemotherapy group (Pac); the paclitaxel+ parecoxib sodium intervention group (Pac + Pare); and the parecoxib sodium group (Pare). We observed changes in alveolar ventilation function, alveolar-capillary membrane permeability, lung tissue pathology and measured the levels of inflammatory cytokines and cyclooxygenase-2 (Cox-2) in lung tissue, the expression of tight junction proteins (Zo-1 and Claudin-4). Compared with the Con group, the lung tissue of the Pac group showed significantly increased expression of Cox-2 protein (p < 0.01), significant lung tissue inflammatory changes, significantly increased expression of inflammatory cytokines, decreased expression of Zo-1 and Claudin-4 proteins (p < 0.01), increased alveolar capillary membrane permeability (p < 0.01), and reduced ventilation function (p < 0.01). Notably, in Pac + Pare group, intraperitoneal injection of parecoxib sodium led to decreased Cox-2 and ICAM-1 levels and reduced inflammatory responses, the recovered expression of Zo-1 and Claudin-4, reduced level of indicators reflecting the high permeability state, and close-to-normal levels of ventilation function. Intervention by the Cox-2-specific inhibitor parecoxib sodium can block this damage. PMID- 26256767 TI - Col2-Cre and tamoxifen-inducible Col2-CreER target different cell populations in the knee joint. AB - OBJECTIVE: Collagen type 2 (Col2)-Cre or tamoxifen-inducible Col2-CreER transgenic mouse lines have been used for studies to explore the cellular and molecular pathogenesis of osteoarthritis (OA). The purpose of this study is to investigate whether the targeted cells are the same or different in the two mouse lines. METHODS: We crossed tamoxifen inducible Col2-CreER and Col2-Cre mice with Rosa tdTomato reporter mice and analyzed the labeling patterns at different time points. RESULTS: In the Col2-CreER mice, 90.8 [95% confidence interval (CI) (88.3, 93.2)] and 82.8 (77.4, 88.3) % of the articular surface cells are Tomato positive when tamoxifen was administered at 2 and 2.5 weeks of age and strong activity was observed even 4.5 months after injection. However, 46.0 (32.8, 59.1) and 22.2 (11.7, 32.6) % of the surface cells were Tomato positive when tamoxifen was administered at 3 and 4 weeks of age, respectively. Little to no Tomato activity in the articular surface cells was observed when tamoxifen was administered at 8 weeks of age. At any stage of tamoxifen injection, the Tomato activity was detected in growth plate and epiphyseal bone in addition to articular chondrocytes, but little in endosteum and not in the synovium and ligament. In contrast, the targeted tissues in the Col2-Cre mouse line were articular cartilage, growth plate, meniscus, endosteum, ligament, bone and synovium. CONCLUSIONS: This study demonstrates that the pattern of targeted cells in the inducible Col2-CreER mice are partially overlapping with but different from that of targeted cells in Col2-Cre mice and the pattern varies dependent on when tamoxifen is administered. PMID- 26256766 TI - Systemic administration of strontium or NBD peptide ameliorates early stage cartilage degradation of mouse mandibular condyles. AB - OBJECTIVE: To determine whether mandibular condylar cartilage degradation induced by experimentally abnormal occlusion could be ameliorated via systemic administration of strontium or NBD peptide. METHODS: Six-week-old female C57BL/6J mice were used. From the seventh day after mock operation or unilateral anterior crossbite (UAC) treatment, the control and UAC mice were further respectively pharmacologically treated for 2 weeks or 4 weeks of saline (CON + Saline and UAC + Saline groups), SrCl2 (CON + SrCl2 and UAC + SrCl2 groups) or NBD peptide (CON + NBD peptide and UAC + NBD peptide groups). Changes in condylar cartilage and subchondral bone were assessed 21 and 35 days after mock operation or UAC procedure by histology and micro-CT. Real-time PCR and/or immunohistochemistry (IHC) were performed to evaluate changes in expression levels of col2a1, aggrecan, ADAMTS-5, tnf-alpha, il-1beta, nfkbia, nuclear factor-kappaB phospho p65 in condylar cartilage, and rankl/rank/opg in both condylar cartilage and subchondral bone. RESULTS: Cartilage degradation with decreased col2a1 and aggrecan expression, and increased ADAMTS-5, tnf-alpha/il1-beta, nfkbia and NF kappaB phospho-p65 was observed in UAC + Saline groups. Subchondral bone loss with increased osteoclast numbers and decreased opg/rankl ratio was found in UAC + Saline groups compared to age-match CON + Saline groups. Cartilage degradation and subchondral bone loss were reversed by treatment of SrCl2 or NBD peptide while the same dosage in control mice induced few changes in condylar cartilage and subchondral bone. CONCLUSIONS: The results demonstrate reverse effect of systemic administration of strontium or NBD peptide on UAC-induced condylar cartilage degradation and subchondral bone loss. PMID- 26256768 TI - Cdon promotes neural crest migration by regulating N-cadherin localization. AB - Neural crest cells (NCCs) are essential embryonic progenitor cells that are unique to vertebrates and form a remarkably complex and coordinated system of highly motile cells. Migration of NCCs occurs along specific pathways within the embryo in response to both environmental cues and cell-cell interactions within the neural crest population. Here, we demonstrate a novel role for the putative Sonic hedgehog (Shh) receptor and cell adhesion regulator, cdon, in zebrafish neural crest migration. cdon is expressed in developing premigratory NCCs but is downregulated once the cells become migratory. Knockdown of cdon results in aberrant migration of trunk NCCs: crestin positive cells can emigrate out of the neural tube but stall shortly after the initiation of migration. Live cell imaging analysis demonstrates reduced directedness of migration, increased velocity and mispositioned cell protrusions. In addition, transplantation analysis suggests that cdon is required cell-autonomously for directed NCC migration in the trunk. Interestingly, N-cadherin is mislocalized following cdon knockdown suggesting that the role of cdon in NCCs is to regulate N-cadherin localization. Our results reveal a novel role for cdon in zebrafish neural crest migration, and suggest a mechanism by which Cdon is required to localize N cadherin to the cell membrane in migratory NCCs for directed migration. PMID- 26256770 TI - Phosphorene: Synthesis, Scale-Up, and Quantitative Optical Spectroscopy. AB - Phosphorene, a two-dimensional (2D) monolayer of black phosphorus, has attracted considerable theoretical interest, although the experimental realization of monolayer, bilayer, and few-layer flakes has been a significant challenge. Here, we systematically survey conditions for liquid exfoliation to achieve the first large-scale production of monolayer, bilayer, and few-layer phosphorus, with exfoliation demonstrated at the 10 g scale. We describe a rapid approach for quantifying the thickness of 2D phosphorus and show that monolayer and few-layer flakes produced by our approach are crystalline and unoxidized, while air exposure leads to rapid oxidation and the production of acid. With large quantities of 2D phosphorus now available, we perform the first quantitative measurements of the material's absorption edge-which is nearly identical to the material's band gap under our experimental conditions-as a function of flake thickness. Our interpretation of the absorbance spectrum relies on an analytical method introduced in this work, allowing the accurate determination of the absorption edge in polydisperse samples of quantum-confined semiconductors. Using this method, we found that the band gap of black phosphorus increased from 0.33 +/- 0.02 eV in bulk to 1.88 +/- 0.24 eV in bilayers, a range that is larger than that of any other 2D material. In addition, we quantified a higher-energy optical transition (VB-1 to CB), which changes from 2.0 eV in bulk to 3.23 eV in bilayers. This work describes several methods for producing and analyzing 2D phosphorus while also yielding a class of 2D materials with unprecedented optoelectronic properties. PMID- 26256769 TI - A Multicomponent Intervention to Improve Primary Care Provider Adherence to Chronic Opioid Therapy Guidelines and Reduce Opioid Misuse: A Cluster Randomized Controlled Trial Protocol. AB - BACKGROUND: Prescription opioid misuse is a significant public health problem as well as a patient safety concern. Primary care providers (PCPs) are the leading prescribers of opioids for chronic pain, yet few PCPs follow standard practice guidelines regarding assessment and monitoring. This cluster randomized controlled trial will determine whether four implementation strategies; nurse care management, use of a patient registry, academic detailing, and electronic tools, will increase PCP adherence to chronic opioid therapy guidelines and reduce opioid misuse among patients, relative to electronic tools alone. The implementation strategies and intervention content are based on the chronic care model. METHODS: We include 53 PCPs from three Boston-area community health centers and one urban safety-net hospital-based primary care practice who have at least four patients meeting the following inclusion criteria: 1) age>=18; 2) one or more completed visits to the primary care practice in the past year; 3) long term opioid treatment defined as three or more opioid prescriptions written at least 21days apart within 6months and 4) an inpatient or outpatient ICD-9-CM diagnosis for musculoskeletal or neuropathic pain. We consider PCPs to be study subjects, and obtained a waiver of informed consent for patients because the study is promoting an established standard of care. We enrolled participants (PCPs) from December 2012 through March 2015. PCPs were randomized to receive the intervention, which includes four components: 1) nurse care management, 2) use of a patient registry, 3) academic detailing, and 4) electronic tools, or a control condition, which includes only the use of the electronic tools. The intervention PCPs receive the services of a nurse-managed registry for planning individual patient care and conducting population-based care for patients receiving opioids for chronic pain. In academic detailing visits, trained co-investigators provide intervention PCPs with individualized education to change prescribing practice. Electronic tools, located on a web site external to the EMR, www.mytopcare.org, include validated instruments to assess patient status, and management resources to facilitate PCP adherence to suggested monitoring. Electronic tools are available to PCPs in both study arms. The primary outcomes are PCP adherence to chronic opioid therapy guidelines and patient opioid misuse. Secondary outcomes include measures of substance abuse, possible opioid diversion, and level of opioid risk among patients. We will follow PCPs and their estimated 1200 chronic pain patients for 1year after study enrollment. To determine whether the intervention condition achieves greater adherence to guidelines and reduced opioid misuse after 1year compared to the control condition, we will compare the baseline and follow-up measures of the individual patients, stratifying by intervention status and noting differences that are statistically significant at the p=0.05 level. Analyses will be based on intent-to-treat. RESULTS: Randomization resulted in groups with similar baseline characteristics. The ages of PCPs are evenly distributed, with inclusion of both PCPs who have recently completed training and those who have been in practice for more than 20years. Two thirds of enrolled PCPs are women, and one-third are non-white. DISCUSSION: The study will determine the impact of this multicomponent intervention on improving PCP adherence to guidelines and reducing opioid misuse among patients. PMID- 26256771 TI - Detecting a Local Cohort Effect for Cancer Mortality Data Using a Varying Coefficient Model. AB - BACKGROUND: Cancer mortality is increasing with the aging of the population in Japan. Cancer information obtained through feasible methods is therefore becoming the basis for planning effective cancer control programs. There are three time related factors affecting cancer mortality, of which the cohort effect is one. Past descriptive epidemiologic studies suggest that the cohort effect is not negligible in cancer mortality. METHODS: In this paper, we develop a statistical method for automatically detecting a cohort effect and assessing its statistical significance for cancer mortality data using a varying coefficient model. RESULTS: The proposed method was applied to liver and lung cancer mortality data on Japanese men for illustration. Our method detected significant positive or negative cohort effects. The relative risk was 1.54 for liver cancer mortality in the cohort born around 1934 and 0.83 for lung cancer in the cohort born around 1939. CONCLUSIONS: Cohort effects detected using the proposed method agree well with previous descriptive epidemiologic findings. In addition, the proposed method is expected to be sensitive enough to detect smaller, previously undetected birth cohort effects. PMID- 26256772 TI - Dynapenic Obesity and Prevalence of Type 2 Diabetes in Middle-Aged Japanese Men. AB - BACKGROUND: The independent and combined associations of muscle strength and obesity on the prevalence of type 2 diabetes in Japanese men remain unclear. METHODS: Hand grip strength was cross-sectionally evaluated between 2011 and 2013 to assess muscle strength in 5039 male workers aged 40 to 64 years. Weight and height were measured, and overweight/obesity was defined as a body mass index >=25 kg/m(2). The prevalence of type 2 diabetes, defined as fasting plasma glucose >=126 mg/dL and/or hemoglobin A1c >=6.5% and/or self-reported physician diagnosed diabetes, was evaluated. Odds ratios (OR) and 95% confidence intervals (95% CI) for the prevalence of type 2 diabetes were obtained using a logistic regression model. RESULTS: In total, 611 participants had type 2 diabetes, and 1763 participants were overweight/obese. After adjustment for covariates, we found an inverse association between muscle strength and the prevalence of type 2 diabetes (P for trend <0.01). In addition, when the analyses were stratified by obesity status, the multivariable-adjusted OR per 2-standard-deviation increase in muscle strength was 0.64 (95% CI, 0.49-0.83) in the overweight/obese group, compared to a weaker relationship in the normal-weight group (OR 0.79 per 2 standard-deviation increase; 95% CI, 0.60-1.06). CONCLUSIONS: Dynapenia, an age related decrease in muscle strength, is associated with increased prevalence of type 2 diabetes, and this relationship is stronger in overweight/obese middle aged Japanese men than in normal-weight men. PMID- 26256773 TI - Splenectomy Correlates With Increased Risk of Pyogenic Liver Abscess: A Nationwide Cohort Study in Taiwan. AB - OBJECTIVES: Little is known about the risk of pyogenic liver abscess in patients with splenectomy. We explored the relationship between splenectomy and pyogenic liver abscess in Taiwan. METHODS: We conducted a nationwide cohort analysis using the hospitalization dataset of the Taiwan National Health Insurance Program. We included 17,779 subjects aged 20-84 years who underwent splenectomy in 1998 to 2010 (splenectomy group) and 70,855 randomly selected subjects without splenectomy (non-splenectomy group). Both groups were matched by sex, age, other comorbidities, and hospitalization year of receiving splenectomy. The incidence of pyogenic liver abscess at the end of 2011 was measured. The multivariable Cox proportional hazard regression model was used to estimate the hazard ratios and 95% confidence intervals for pyogenic liver abscess associated with splenectomy and other comorbidities. RESULTS: The overall incidence rate was 3.75-fold higher in the splenectomy group than that in the non-splenectomy group (2.15 vs 0.57 per 1000 person-years; 95% confidence interval, 3.57-3.94). After controlling for potential confounding factors, the adjusted hazard ratio of pyogenic liver abscess was 3.89 in subjects with splenectomy (95% confidence interval, 3.20 4.72) when compared with subjects without splenectomy. In further analysis, the hazard ratio markedly increased to 14.34 for those with splenectomy and having any of the assessed comorbidities, including alcoholism, biliary stone, chronic kidney disease, chronic liver diseases, and diabetes mellitus (95% confidence interval, 10.61-19.39). CONCLUSIONS: Patients with splenectomy are at an increased risk of developing pyogenic liver abscess, particularly when they have comorbid conditions. PMID- 26256774 TI - Factor structure of the Childhood Autism Rating Scale as per DSM-5. AB - BACKGROUND: The DSM-5 recently proposed new diagnostic criteria for autism spectrum disorder (ASD). Although many new or updated tools have been developed since the DSM-IV was published in 1994, the Childhood Autism Rating Scale (CARS) has been used consistently in ASD diagnosis and research due to its technical adequacy, cost-effectiveness, and practicality. Additionally, items in the CARS did not alter following the release of the revised DSM-IV because the CARS factor structure was found to be consistent with the revised criteria after factor analysis. For that reason, in this study confirmatory factor analysis was used to identify the factor structure of the CARS. METHOD: Participants (n = 150) consisted of children with an ASD diagnosis or who met the criteria for broader autism or emotional/behavior disorder with comorbid disorders such as attention deficit hyperactivity disorder, bipolar disorder, intellectual or developmental disabilities. Previous studies used one-, two-, and four-factor models, all of which we examined to confirm the best-fit model on confirmatory factor analysis. RESULTS: Appropriate comparative fit indices and root mean square errors were obtained for all four models. The two-factor model, based on DSM-5 criteria, was the most valid and reliable. The inter-item consistency of the CARS was 0.926 and demonstrated adequate reliability, thereby supporting the validity and reliability of the two-factor model of CARS. CONCLUSIONS: Although CARS was developed prior to the introduction of DSM-5, its psychometric properties, conceptual relevance, and flexible administration procedures support its continued role as a screening device in the diagnostic decision-making process. PMID- 26256775 TI - Two microporous MOFs constructed from different metal cluster SBUs for selective gas adsorption. AB - Two microporous MOFs have been constructed from different metal cluster SBUs. Both of them exhibit highly selective CO2 adsorption capacity over CH4 and N2 owing to their abundant active sites. PMID- 26256776 TI - In silico spatial simulations reveal that MCC formation and excess BubR1 are required for tight inhibition of the anaphase-promoting complex. AB - In response to the activation of the mitotic spindle assembly checkpoint (SAC), distinct inhibitory pathways control the activity of the anaphase-promoting complex (APC/C). It remains unclear whether the different regulatory mechanisms function in separate pathways or as part of an integrated signalling system. Here, five variant models of APC/C regulation were constructed and analysed. The simulations showed that all variant models were able to reproduce the wild type behaviour of the APC. However, only one model, which included both the mitotic checkpoint complex (MCC) as well as BubR1 as direct inhibitors of the APC/C, was able to reproduce both wild and mutant type behaviour of APC/C regulation. Interestingly, in this model, the MCC as well as the BubR1 binding rate to the APC/C was comparable to the known Cdc20-Mad2 binding rate and could not be made higher. Mad2 active transport towards the spindle mid-zone accelerated the inhibition speed of the APC/C but not its concentration level. The presented study highlights the principle that a systems biology approach is critical for the SAC mechanism and could also be used for predicting hypotheses to design future experiments. The presented work has successfully distinguished between five potent inhibitors of the APC/C using a systems biology approach. Here, the favoured model contains both BubR1 and MCC as direct inhibitors of the APC/C. PMID- 26256777 TI - Rapid and accurate liquid chromatography and tandem mass spectrometry method for the simultaneous quantification of ten metabolic reactions catalyzed by hepatic cytochrome P450 enzymes. AB - The hepatic cytochrome P450 enzymes play a central role in the biotransformation of endogenous and exogenous substances. A sensitive high-throughput liquid chromatography with tandem mass spectrometry assay was developed and validated for the simultaneous quantification of the products of ten metabolic reactions catalyzed by hepatic cytochrome P450 enzymes. After the substrates were incubated separately, the samples were pooled and analyzed by liquid chromatography with tandem mass spectrometry using an electrospray ionization source in the positive and negative ion modes. The method exhibited linearity over a broad concentration range, insensitivity to matrix effects, and high accuracy, precision, and stability. The novel method was successfully applied to study the kinetics of phenacetin-O deethylation, coumarin-7 hydroxylation, bupropion hydroxylation, taxol-6 hydroxylation, omeprazole-5 hydroxylation, dextromethorphan-O demethylation, tolbutamide-4 hydroxylation, chlorzoxazone-6 hydroxylation, testosterone-6beta hydroxylation, and midazolam-1 hydroxylation in rat liver microsomes. PMID- 26256778 TI - Antiviral therapy in seasonal influenza and 2009 H1N1 pandemic influenza: Korean experiences and perspectives. AB - Influenza is a major cause of substantial morbidity and mortality in humans every year. Vaccination is the main strategy to prevent influenza infection, but antiviral agents also play an important role in the control of both seasonal and pandemic influenza. During the influenza A/H1N1 pandemic in 2009, early prompt antiviral therapy may have reduced the severity of the influenza outcomes including pneumonia, hospitalization and mortality in the Republic of Korea. Since the 2009 H1N1 pandemic, there have been increasing usages of antiviral agents for the treatment of patients with seasonal influenza. Although currently rare, antiviral resistance among influenza viruses may emerge and increase with increased use of neuraminidase inhibitors. New agents with different modes of action are under investigation, including favipiravir, DAS181, nitazoxanide and broad-spectrum neutralizing monoclonal antibodies. Data are limited with respect to high-dose and combination antiviral therapies. So, clinical trials are warranted to evaluate diverse antiviral combinations that may be synergistic and less likely to induce breakthrough resistance. PMID- 26256781 TI - Role, perspective and knowledge of Iranian critical care nurses about breaking bad news. AB - BACKGROUND: Given the issue of caring critically ill patients, nurses are involved in the process of breaking bad news in critical care units, while little research has been conducted on this challenging issue. OBJECTIVES: The purpose of this study was to determine the role, perspective and knowledge of Iranian critical care nurses regarding breaking bad news. METHODS: This descriptive study was conducted on a sample of 160 nurses working in critical care units of hospitals affiliated to Tehran University of Medical Sciences. Stratified and quota sampling methods were used. The data collection tool was a four-part questionnaire with validity and reliability confirmed via content validity and test-retest, respectively. RESULTS: The study showed that most critical care nurses were involved in breaking bad news, with different roles. The majority of participants (91.2%) had a positive attitude towards involvement of nurses in breaking bad news. In this study, 78.8% of nurses had moderate knowledge about how to break bad news, and only a few had good level of knowledge (16.2%). CONCLUSION: According to the findings, while critical care nurses took different roles in the process of breaking bad news and they had positive attitude towards participation in this process, yet their knowledge about this process was inadequate. Thus, designing educational programmes to enhance critical care nurses' knowledge and skills in this area seems necessary. PMID- 26256782 TI - Sequence-based typing characterization of the novel HLA-DRB3*01:16 allele, identified in an Italian family. AB - The novel DRB1*01:16 allele differs for G to T substitution at position 595 from DRB3*01:01P. PMID- 26256783 TI - A modified Kampala trauma score (KTS) effectively predicts mortality in trauma patients. AB - BACKGROUND: Mortality prediction in trauma patients has relied upon injury severity scoring tools focused on anatomical injury. This study sought to examine whether an injury severity scoring system which includes physiologic data performs as well as anatomic injury scores in mortality prediction. METHODS: Using data collected from 18 Level I trauma centers and 51 non-trauma center hospitals in the US, anatomy based injury severity scores (ISS), new injury severity scores (NISS) were calculated as were scores based on a modified version of the physiology-based Kampala trauma score (KTS). Because pre-hospital intubation, when required, is standard of care in the US, a modified KTS was calculated excluding respiratory rate. The predictive ability of the modified KTS for mortality was compared with the ISS and NISS using receiver operating characteristic (ROC) curves. RESULTS: A total of 4716 individuals were eligible for study. Each of the three scores was a statistically significant predictor of mortality. In this sample, the modified KTS significantly outperformed the ISS (AUC=0.83, 95% CI 0.81-0.84 vs. 0.77, 95% CI 0.76-0.79, respectively) and demonstrated similar predictive ability compared to the NISS (AUC=0.83, 95% CI 0.81-0.84 vs. 0.82, 95% CI 0.80-0.83, respectively). CONCLUSIONS: The modified KTS may represent a useful tool for assessing trauma mortality risk in real time, as well as in administrative data where physiologic measures are available. Further research is warranted and these findings suggest that the collection of physiologic measures in large databases may improve outcome prediction. PMID- 26256784 TI - Total and subtotal amputation of lower limbs treated by acute shortening, revascularization and early limb lengthening with ilizarov ring fixation - a retrospective study. AB - We present the results of 15 patients who sustained total or subtotal traumatic amputation of the lower limbs who were treated by acute limb shortening and stabilisation with external fixator, revascularization and early lengthening with Ilizarov ring fixator. The mean age of the patients was 28 years [5-38]. There were three females and 12 males. The mean Mangled Extremity Severity Score was 8.5 [range 6-11]. The mean amount of shortening done was 6.9cm [range 3-12.5] to enable revascularization and soft tissue repair. Three cases had to be amputated early because of failure of vascular repair. In the remaining 12 patients who were followed up the mean interval between revascularization and application of Ilizarov ring fixator was 4.7 weeks [range 3-10]. The mean follow up was 6.5 years [3-16 years]. Union occurred in all patients. Ten of the 12 patients returned to work and residual shortening was present in two cases. We conclude that whenever possible lower limb salvage should be undertaken. PMID- 26256785 TI - The clamshell incision can be easily taught to both emergency physicians and surgeons. PMID- 26256786 TI - RNF8 deficiency results in neurodegeneration in mice. AB - The progressive loss of neurons causes neurodegenerative diseases. Because the accumulation of DNA breaks results in neuronal apoptosis, the lack of a variety of DNA damage repair-related proteins contributes to neurodegeneration. The ubiquitin ligase RNF8 plays an important role in DNA double-strand break repair via histone ubiquitination. However, the function of RNF8 in terminally differentiated neurons remains unknown. This study aimed to determine whether RNF8 is involved in the DNA damage response in neurons and contributes to neurodegeneration. Here, we present evidence suggesting that RNF8 deficiency results in DNA damage accumulation and neuronal apoptosis. RNF8(-/-) mice exhibit neuronal degeneration and reactive astrocytosis. Neurons from RNF8(-/-) mice appear to be more susceptible to X-ray-induced DNA damage. These changes were consistent with the behavioral performances of the RNF8-deficient mice, which included impaired performances in the open-field test and step-down avoidance task. Overall, these findings show that RNF8 is required for DNA damage repair in neurons. RNF8 deficiency is sufficient to cause neuronal pathology and cognitive decline, and the loss of RNF8 results in neuron degeneration. PMID- 26256787 TI - Sulcal morphology as a new imaging marker for the diagnosis of early onset Alzheimer's disease. AB - We investigated the utility of sulcal width measures in the diagnosis of Alzheimer's disease (AD). Sixty-six biologically confirmed AD patients (positive amyloid positron emission tomography [PET] and/or AD cerebrospinal fluid profile) were contrasted to 35 controls with negative amyloid PET. Patients were classified into prodromal or dementia stages as well as into late onset (LOAD, n = 31) or early onset (EOAD, n = 35) subgroups according to their age of onset. An automated method was used to calculate sulcal widths and hippocampal volumes (HV). In EOAD, the greatest ability to differentiate patients from age-matched controls, regardless of severity, was displayed by sulcal width of the temporoparietal cortex. In this region, diagnosis accuracy was better than the HV, especially at prodromal stage. In LOAD, HV provided the best discrimination power from age-matched controls. In conclusion, sulcal width measures are better markers than the HV for identifying prodromal AD in patients aged <65 years. In contrast, in older patients, the risk of over-diagnosis from using only sulcal enlargement is important. PMID- 26256788 TI - The yin and yang of hepatitis C: synthesis and decay of hepatitis C virus RNA. AB - Hepatitis C virus (HCV) is an unusual RNA virus that has a striking capacity to persist for the remaining life of the host in the majority of infected individuals. In order to persist, HCV must balance viral RNA synthesis and decay in infected cells. In this Review, we focus on interactions between the positive sense RNA genome of HCV and the host RNA-binding proteins and microRNAs, and describe how these interactions influence the competing processes of viral RNA synthesis and decay to achieve stable, long-term persistence of the viral genome. Furthermore, we discuss how these processes affect hepatitis C pathogenesis and therapeutic strategies against HCV. PMID- 26256791 TI - Jumping depends on impulse not power. PMID- 26256789 TI - Bacterial protein networks: properties and functions. AB - Distinct cellular functions are executed by separate groups of proteins, organized into complexes or functional modules, which are ultimately interconnected in cell-wide protein networks. Understanding the structures and operational modes of these networks is one of the next great challenges in biology, and microorganisms are at the forefront of research in this field. In this Review, we present our current understanding of bacterial protein networks, their general properties and the tools that are used for systematically mapping and characterizing them. We then discuss two well-studied examples, the chemotaxis network and the cell cycle network in Escherichia coli, to illustrate how network architecture promotes function. PMID- 26256790 TI - Baicalin Protects Keratinocytes from Toll-like Receptor-4 Mediated DNA Damage and Inflammation Following Ultraviolet Irradiation. AB - UVB radiation contributes to both direct and indirect damage to the skin including the generation of free radicals and reactive oxygen species (ROS), inflammatory responses, immunosuppression and gene mutations, which can ultimately lead to photocarcinogenesis. A plant-derived flavonoid, baicalin, has been shown to have antioxidant, anti-inflammatory and free radical scavenging activities. Previous studies from our laboratory have shown that in murine skin, Toll-like receptor-4 (TLR4) enhanced both UVB-induced DNA damage and inflammation. The aim of this study was to investigate the efficacy of baicalin against TLR4-mediated processes in the murine keratinocyte PAM 212 cell line. Our results demonstrate that treating keratinocytes with baicalin both before and after UV radiation (100 mJ cm(-2) ) significantly inhibited the level of intracellular ROS and decreased cyclobutane pyrimidine dimers and 8-Oxo-2' deoxyguanosine (8-oxo-dG)-markers of DNA damage. Furthermore, cells treated with baicalin demonstrated an inhibition of TLR4 and its downstream signaling molecules, MyD88, TRIF, TRAF6 and IRAK4. TLR4 pathway inhibition resulted in NF kappaB inactivation and down-regulation of iNOS and COX-2 protein expression. Taken together, baicalin treatment effectively protected keratinocytes from UVB induced inflammatory damage through TLR pathway modulation. PMID- 26256792 TI - Microcirculation abnormalities provoked by Loxosceles spiders' envenomation. AB - Loxoscelism is caused by envenomation by spiders from Loxosceles genus. Clinical symptoms only appear a few hours after envenomation and can evolve in local reactions, such as dermonecrosis, and systemic reactions, including intravascular haemolysis, intravascular coagulation and renal failure. Considering that alterations in the microcirculatory network are involved in the pathogenesis of different diseases, including the inflammatory process, the aim of this study was to investigate the action of venoms of males and females of Loxosceles intermedia and Loxosceles laeta on the microcirculatory network and examine the systemic production of inflammatory mediators in a murine model of loxoscelism. We observed that during systemic envenomation, the alterations in the microcirculation include increase in the number of rolling cells, which was more intense in animals injected with female Loxosceles spider venoms. This positively correlated with increase in TNF-alpha and NO serum levels, induction of which was higher by female venoms when compared with male venoms. The increase of leukocytes rolling was not accompanied by increase of cell adhesion. The absence of leukocyte extravasation may explain why in mice, in contrast to humans, no cutaneous loxoscelism occurs. Thus, targeting the neutrophil adhesion and extravasation in Loxosceles envenomed patients may prevent cutaneous pathology. PMID- 26256793 TI - Feeding an army: The metabolism of T cells in activation, anergy, and exhaustion. AB - Through the direct control of infection or by providing cytokine signals to other cellular players, T cells play a central role in the orchestration of the immune response. However, in many disease states, T cells are rendered dysfunctional, unable to carry out their effector functions. As T cell activation is bioenergetically demanding, some T cell dysfunction can have metabolic underpinnings. In this review, we will discuss how T cells are programmed to fuel their effector response, and how programmed or pathologic changes can disrupt their ability to generate the energy needed to proliferate and carry out their critical functions. PMID- 26256795 TI - Glucose-based dialysis fluids inhibit innate defense against Staphylococcus aureus. AB - BACKGROUND: Staphylococcus aureus peritonitis is a serious complication of Chronic Peritoneal Dialysis (CPD) and associated with a higher risk for severe and recurrent infections compared with other bacteria. We have previously shown that complement-mediated effectors essential for optimal opsonophagocytosis of S. aureus are inhibited by high glucose concentrations. Since most commonly used peritoneal dialysis (PD) fluids are glucose-based, we hypothesized that glucose based PD fluids likely inhibit complement host defenses against S. aureus. METHODS: Commercially available PD fluids were tested: glucose-based (Dianeal), Dianeal supplemented with amino acids, icodextrin-based (Extraneal) and amino acid-based (Nutrineal). Control PD fluid was generated to simulate Dianeal excluding the glucose. Three commercially available glucose concentrations were tested: Dianeal 1.5% (15 gm/1000 ml), Dianeal 2.5% (25 gm/1000 ml) and Dianeal 4.25% (42.5 gm/1000 ml). Complement effectors against S. aureus were analyzed including opsonization with C3-fragments, anaphylatoxin generation, and phagocytosis efficiency. We also evaluated clinical strains, including MRSA strains, and specific complement activation pathways. RESULTS: Glucose-based PD fluids inhibited complement opsonization of S. aureus (>=7-fold reduction) and inhibited S. aureus-induced generation of anaphylatoxins C3a and C5a (>10-fold reduction) compared to non-glucose based PD fluids. Dianeal 1.5%, 2.5% and 4.25%, all similarly inhibited C3-mediated opsonization. Glucose-based PD fluids showed a >=4-fold reduction in opsonization of clinical strains of S.aureus, including MRSA strains. Decreased opsonization of S.aureus in the glucose-based PD fluid compared with non-glucose based fluids correlated with decreased phagocytosis by neutrophils. CONCLUSION: Complement-mediated opsonophagocytosis of S. aureus and anaphylatoxin generation were severely inhibited in glucose-based PD fluids compared with non-glucose-based PD fluids. By inhibiting complement host defenses, glucose-based PD fluids may increase the risk of and severity of S. aureus peritonitis for CPD patients using these fluids. PMID- 26256794 TI - ErbB3 binding protein 1 (EBP1) participates in the regulation of intestinal inflammation via mediating Akt signaling pathway. AB - ErbB3 binding protein-1 (EBP1) belongs to a family of DNA/RNA binding proteins implicated in cell growth, differentiation and apoptosis. Previous data demonstrated that EBP1 regulates phosphorylation of Akt to drive tumor progress. However, the expression and biological functions of EBP1 in ulcerative colitis (UC) remain unclear. In this study, we reported for the first time that EBP1 was down-regulated in intestinal epithelial cell (IECs) of patients with UC. In DSS induced colitis, we observed the down-regulation of EBP1 accompanied with the elevated levels of proinflammatory cytokines (IL-1beta, IL-6 and IL-8) and Akt activation indicators (phosphorylated Akt) in colitis IECs, indicating the possible involvement of EBP1 in regulation of intestinal inflammation via mediating Akt in UC. Employing the TNF-alpha-treated HT-29 cells as an IEC inflammatory model, we confirmed the negative correlation of EBP1 with Akt activation and Akt-dependent inflammation progress in vitro. EBP1 knocking down and over-expression significantly regulated TNF-alpha-induced Akt activation and proinflammatory cytokines expression in HT-29 cells. Taken together, our data suggested that EBP1 participates in the regulation of intestinal inflammation via mediating Akt signaling pathway. PMID- 26256797 TI - Recent advances in the application of capillary electromigration methods for food analysis and Foodomics. AB - This review work presents and discusses the main applications of capillary electromigration methods in food analysis and Foodomics. Papers that were published during the period February 2013-February 2015 are included following the previous review by Garcia-Canas et al. (Electrophoresis, 2014, 35, 147-169). Analysis by CE of a large variety of food-related molecules with different chemical properties, including amino acids, hazardous amines, peptides, proteins, phenols, polyphenols, lipids, carbohydrates, DNAs, vitamins, toxins, contaminants, pesticides, residues, food additives, as well as small organic and inorganic compounds. This work includes recent results on food quality and safety, nutritional value, storage, bioactivity, as well as applications of CE for monitoring food processing. The use, among other CE developments, of microchips, CE-MS, and chiral CE in food analysis and Foodomics is also discussed. PMID- 26256798 TI - Structural and energetic insight into the interactions between the benzolactam inhibitors and tumor marker HSP90alpha. AB - The heat shock protein 90alpha (HSP90alpha) provides a promising molecular target for cancer therapy. A series of novel benzolactam inhibitors exhibited distinct inhibitory activity for HSP90alpha. However, the structural basis for the impact of distinct R1 substituent groups of nine benzolactam inhibitors on HSP90alpha binding affinities remains unknown. In this study, we carried out molecular docking, molecular dynamics (MD) simulations, and molecular mechanics and generalized Born/surface area (MM-GBSA) binding free energy calculations to address the differences. Molecular docking studies indicated that all nine compounds presented one conformation in the ATP-binding site of HSP90alpha N terminal domain. MD simulations and subsequent MM-GBSA calculations revealed that the hydrophobic interactions between all compounds and HSP90alpha contributed the most to the binding affinity and a good linear correlation was obtained between the calculated and the experimental binding free energies (R=0.88). The per residue decomposition revealed that the most remarkable differences of residue contributions were found in the residues Ala55, Ile96, and Leu107 defining a hydrophobic pocket for the R1 group, consistent with the analysis of binding modes. This study may be helpful for the future design of novel HSP90alpha inhibitors. PMID- 26256799 TI - Analysis of image-based phenotypic parameters for high throughput gene perturbation assays. AB - Although image-based phenotypic assays are considered a powerful tool for siRNA library screening, the reproducibility and biological implications of various image-based assays are not well-characterized in a systematic manner. Here, we compared the resolution of high throughput assays of image-based cell count and typical cell viability measures for cancer samples. It was found that the optimal plating density of cells was important to obtain maximal resolution in both types of assays. In general, cell counting provided better resolution than the cell viability measure in diverse batches of siRNAs. In addition to cell count, diverse image-based measures were simultaneously collected from a single screening and showed good reproducibility in repetitions. They were classified into a few functional categories according to biological process, based on the differential patterns of hit (i.e., siRNAs) prioritization from the same screening data. The presented systematic analyses of image-based parameters provide new insight to a multitude of applications and better biological interpretation of high content cell-based assays. PMID- 26256800 TI - MATEPRED-A-SVM-Based Prediction Method for Multidrug And Toxin Extrusion (MATE) Proteins. AB - The growth and spread of drug resistance in bacteria have been well established in both mankind and beasts and thus is a serious public health concern. Due to the increasing problem of drug resistance, control of infectious diseases like diarrhea, pneumonia etc. is becoming more difficult. Hence, it is crucial to understand the underlying mechanism of drug resistance mechanism and devising novel solution to address this problem. Multidrug And Toxin Extrusion (MATE) proteins, first characterized as bacterial drug transporters, are present in almost all species. It plays a very important function in the secretion of cationic drugs across the cell membrane. In this work, we propose SVM based method for prediction of MATE proteins. The data set employed for training consists of 189 non-redundant protein sequences, that are further classified as positive (63 sequences) set comprising of sequences from MATE family, and negative (126 sequences) set having protein sequences from other transporters families proteins and random protein sequences taken from NCBI while in the test set, there are 120 protein sequences in all (8 in positive and 112 in negative set). The model was derived using Position Specific Scoring Matrix (PSSM) composition and achieved an overall accuracy 92.06%. The five-fold cross validation was used to optimize SVM parameter and select the best model. The prediction algorithm presented here is implemented as a freely available web server MATEPred, which will assist in rapid identification of MATE proteins. PMID- 26256801 TI - An efficient approach for the prediction of ion channels and their subfamilies. AB - Ion channels are integral membrane proteins that are responsible for controlling the flow of ions across the cell. There are various biological functions that are performed by different types of ion channels. Therefore for new drug discovery it is necessary to develop a novel computational intelligence techniques based approach for the reliable prediction of ion channels families and their subfamilies. In this paper random forest based approach is proposed to predict ion channels families and their subfamilies by using sequence derived features. Here, seven feature vectors are used to represent the protein sample, including amino acid composition, dipeptide composition, correlation features, composition, transition and distribution and pseudo amino acid composition. The minimum redundancy and maximum relevance feature selection is used to find the optimal number of features for improving the prediction performance. The proposed method achieved an overall accuracy of 100%, 98.01%, 91.5%, 93.0%, 92.2%, 78.6%, 95.5%, 84.9%, MCC values of 1.00, 0.92, 0.88, 0.88, 0.90, 0.79, 0.91, 0.81 and ROC area values of 1.00, 0.99, 0.99, 0.99, 0.99, 0.95, 0.99 and 0.96 using 10-fold cross validation to predict the ion channels and non-ion channels, voltage gated ion channels and ligand gated ion channels, four subfamilies (calcium, potassium, sodium and chloride) of voltage gated ion channels, and four subfamilies of ligand gated ion channels and predict subfamilies of voltage gated calcium, potassium, sodium and chloride ion channels respectively. PMID- 26256802 TI - Cavities create a potential back door in epoxide hydrolase Rv1938 from Mycobacterium tuberculosis-A molecular dynamics simulation study. AB - Mycobacterium tuberculosis (Mtb) is the causative organism of tuberculosis. Extensively drug resistant strains and latency have posed formidable challenges in the treatment of tuberculosis. The current study addresses an alpha/beta hydrolase fold bearing enzyme, epoxide hydrolase Rv1938 from Mtb. Epoxide hydrolases are involved in detoxification processes, catabolism and regulation of signaling molecules. Using GROMACS, a 100ns Molecular Dynamics (MD) simulation was performed for Rv1938. Cavities were identified within the protein at various time frames of the simulation and their volumes were computed. During MD simulation, in addition to the substrate binding cavity, opening of two new cavities located behind the active site was observed. These cavities may be similar to the backdoor proposed for acetylcholinesterase. Structural superimposition of epoxide hydrolase from Mtb with the epoxide hydrolase of Agrobacterium radiobacter1 AD1 (Ephy) indicates that cavity1 in Mtb lies at an identical position to that of the water tunnel in Ephy. Further, docking of the substrate and an inhibitor with protein structures obtained from MD simulation at various time frames was also performed. The potential role of these cavities is discussed. PMID- 26256803 TI - Physical activity, sedentary behavior time and lipid levels in the Observation of Cardiovascular Risk Factors in Luxembourg study. AB - BACKGROUND: Recently attention has been drawn to the health impacts of time spent engaging in sedentary behaviors. While many studies have investigated general physical activity (PA) in relation to blood lipid levels, the current study aimed to examine the intensity of activity, including sedentary behavior time, and time spent engaging in moderate and intense PA, with concentrations of HDL and LDL cholesterol, total cholesterol, and triglycerides. METHODS: Participants comprised 1331 individuals, aged 18 to 70 years, from the Observation of Cardiovascular Risk Factors in Luxembourg (ORISCAV-LUX) study, who underwent objective cardiovascular health assessments and completed the International Physical Activity Questionnaire (IPAQ). Time spent engaging in sedentary behaviors (screen time on a workday and a day off, and total sitting time on a work day), and moderate and intense PA, were related to levels of HDL and LDL cholesterol, total cholesterol, and triglycerides. Analyses were conducted in the whole sample, and then with stratification according to BMI (normal weight versus overweight/obese). RESULTS: Both lower screen time during days off and higher intense PA time were significantly associated with higher HDL-cholesterol after full adjustment for socio-demographic factors, dietary factors and smoking (both p < 0.05). In normal weight individuals, consistent positive relations between triglycerides, LDL, and total cholesterol with all sedentary behavior time variables were observed (all p < 0.05; adjusted for age, education, gender). There were no statistically significant associations between any intensity level of PA or sedentary behavior time variable and lipid levels in those overweight or obese. CONCLUSIONS: Spending less time in sedentary behaviors, and engaging in medium levels of intense physical activity may be associated with a more favorable blood lipid profile, particularly with regard to levels of HDL and triglycerides. PMID- 26256804 TI - Spherical protein plug in the dilated branch duct of the pancreas. PMID- 26256805 TI - Self-Assembly of Cations in Aqueous Solutions of Hydroxyl-Functionalized Ionic Liquids: Molecular Dynamics Studies. AB - The effect of presence of a hydroxyl-functionalized alkyl chain of varying carbon number on the self-assembly of cations in aqueous solutions of 1-(n-hydroxyalkyl) 3-decylimidazolium bromide (where the alkyl groups are ethyl, butyl, heptyl, and decyl) has been studied using atomistic molecular dynamics simulations. Spontaneous self-assembly of cations to form aggregates with hydrophobic core and hydrophilic surface is observed. The shape of the aggregates changes from quasispherical in the case of cations with hydroxyheptyl or smaller substituent chain, to a thin film like intercalated aggregate in the case of cations with hydroxydecyl chain. Cations with hydroxydecyl substituent chain exhibit long range spatial correlations, and the anions are associated with cations to a greater extent due to the higher surface charge density of the aggregate. The ordered film like aggregate is stabilized by the dispersion interactions between the intercalated substituent chains and the intermolecular hydrogen bonds formed between the alkoxy oxygen atoms and the hydrogen atoms of the imidazolium ring. The cations form less compact aggregates with lower aggregation number than their nonhydroxyl analogues in the corresponding aqueous solutions. The intracationic and aggregate structures are governed by the length of the hydroxyalkyl chain. PMID- 26256806 TI - Mental health inpatient experiences of adults with intellectual disability. AB - This paper presents findings from a study exploring the mental health inpatient care of people with a dual disability of intellectual disability and mental health issues from the perspective of those people with the dual disability. A mixture of semi-structured interviews and focus group interviews were carried out with nine participants who had been admitted to an inpatient unit for mental health care exploring their experience of care. Interviews were transcribed and analyzed using open coding and Leximancer (an online data mining tool) analysis to identify dominant themes in the discourse. Analysis revealed themes around 'Therapeutic and Meaningful Activity', 'Emotion Focussed Care', and 'Feeling Safe?' Participants were able to identify the aspects of inpatient care that worked for them in terms of coping with time in hospital. This research suggests that there are several factors that should be considered in providing effective mental health inpatient care for people with dual disability. A number of strategies and recommendations for responding to their needs are identified and discussed. PMID- 26256807 TI - Antibiotic profiling of Clostridium difficile ribotype 176--A multidrug resistant relative to C. difficile ribotype 027. AB - Antibiotic profiling of twenty Czech Clostridium difficile PCR-ribotype 176 isolates revealed a high level of resistance to erythromycin, ciprofloxacin and moxifloxacin (n = 20) and to rifampicin (n = 13). Accumulation of resistance mechanisms to multiple antibiotics highlight that PCR-ribotype 176 belong to problematic epidemic strains. PMID- 26256808 TI - Fluticasone propionate in clinically suspected asthma patients with negative methacholine challenge test. AB - INTRODUCTION: Despite reports of response to steroid inhaler in some clinically suspected asthma patients with negative methacholine challenge test (CSA/MCT-), treatment in these patients has not been prospectively studied. OBJECTIVE: We studied the role of a 12 week high dose inhaled fluticasone trial in CSA/MCT- patients. METHODS: After a 2 week run-in period, CSA/MCT-patients were treated with 12 weeks of Fluticasone propionate 1000 ug/day. The Asthma Control Test (ACT), numeric cough score (NCS) and bronchodilator use were compared with their pretreatment values. RESULTS: Thirty-four of 42 CSA/MCT-patients completed the study. Mean pretreatment ACT score (pACT) was significantly increased after treatment (14.7 +/- 3.37 to 20.9 +/- 3.1, P < 0.001). Posttreatment values of daytime (1.0 +/- 1.0) and night-time (0.6 +/- 0.9) NCS decreased compared to their pretreatment values (2.8 +/- 1.1 and 1.9 +/- 1.3, respectively; P < 0.001). ACT score change (DeltaACT) were significantly greater in those with pACT < 15 than in those >=15 (P < 0.001) . Fifteen of 21 patients with DeltaACT > 5 did not need to use bronchodilator for their symptom relief. Wheeze disappeared in all six patients with DeltaACT > 5 after the trial. Six months after the study, steroid inhaler continued to be used by 72.2% of patients. CONCLUSION: A significant portion of CSA/MCT- (especially those with pretreatment ACT score <15) respond to high dose fluticasone inhaler in terms of symptoms relief, disappearance of wheeze and need to bronchodilator use. DeltaACT could not be predicted with any individual symptoms or signs before MCT, % FEV1 decline or symptoms during MCT and exhaled nitric oxide. PMID- 26256809 TI - Three-dimensional textural features of conventional MRI improve diagnostic classification of childhood brain tumours. AB - The aim of this study was to assess the efficacy of three-dimensional texture analysis (3D TA) of conventional MR images for the classification of childhood brain tumours in a quantitative manner. The dataset comprised pre-contrast T1 - and T2-weighted MRI series obtained from 48 children diagnosed with brain tumours (medulloblastoma, pilocytic astrocytoma and ependymoma). 3D and 2D TA were carried out on the images using first-, second- and higher order statistical methods. Six supervised classification algorithms were trained with the most influential 3D and 2D textural features, and their performances in the classification of tumour types, using the two feature sets, were compared. Model validation was carried out using the leave-one-out cross-validation (LOOCV) approach, as well as stratified 10-fold cross-validation, in order to provide additional reassurance. McNemar's test was used to test the statistical significance of any improvements demonstrated by 3D-trained classifiers. Supervised learning models trained with 3D textural features showed improved classification performances to those trained with conventional 2D features. For instance, a neural network classifier showed 12% improvement in area under the receiver operator characteristics curve (AUC) and 19% in overall classification accuracy. These improvements were statistically significant for four of the tested classifiers, as per McNemar's tests. This study shows that 3D textural features extracted from conventional T1 - and T2-weighted images can improve the diagnostic classification of childhood brain tumours. Long-term benefits of accurate, yet non-invasive, diagnostic aids include a reduction in surgical procedures, improvement in surgical and therapy planning, and support of discussions with patients' families. It remains necessary, however, to extend the analysis to a multicentre cohort in order to assess the scalability of the techniques used. PMID- 26256810 TI - Mitochondrial DNA Heteroplasmy. AB - Heteroplasmy, the presence of more than one type of mitochondrial DNA (mtDNA) in an individual, holds implications for forensic analysis of specimens such as blood, hair, and skeletal material. That is, what can we conclude about the likelihood that heteroplasmic specimens could or could not be from known individuals? Originally believed to be quite rare in healthy individuals, we now know that heteroplasmy exists at some level in all tissues on a predominantly homoplasmic background. A substantial body of general literature covers the biological origins of heteroplasmy, especially its transmission to new offspring and during life, the methodology for its detection, and its distribution in different tissues. In addition, the forensic community has contributed many observations on the characteristic appearance of heteroplasmy in relevant regions of the mtDNA control region and its appropriate treatment in forensic science. As a result of this growing understanding of a relatively simple biological phenomenon, we conclude that heteroplasmy can be expected to play a role in forensic interpretation on a regular basis, and that knowledge of its biological underpinnings contribute to just, conservative, and scientifically appropriate interpretational guidelines. PMID- 26256811 TI - Single Nucleotide Polymorphisms and Microarray Technology in Forensic Genetics - Development and Application to Mitochondrial DNA. AB - Variations in the genome, due to base substitutions, insertions, or deletions at single positions, are known as single nucleotide polymorphisms (SNPs). Approximately 85% of human variation is based on such polymorphisms. Therefore, there is an abundance of human SNPs that are available for forensic identity testing purposes. SNP analyses also may be suitable for some forensic identity cases, because they can be detected in smallsized amplicons, allowing for genetic analysis of substantially degraded DNA. While SNP analysis is unlikely to replace short tandem repeat loci typing for routine casework, SNPs may prove useful for certain circumstances, for example, typing mitochondrial DNA (mtDNA). Although sequencing mtDNA enables detection of all SNPs contained within the region of interest, it is currently not a practical approach for simultaneously typing SNPs that reside throughout the entire mtDNA genome. A variety of alternate methods to detect SNPs are available that may facilitate mtDNA analysis. All the methods include amplification, typically by the polymerase chain reaction, of the region containing the SNP of interest. Most assays are based on either hybridization of a probe to amplified product or primer extension chemistry, and multiplexing is possible. Some of these methodologies are: chips, SNaP shotTM, Luminex 100TM, SNPstream(r) UHT, and PyrosequencingTM. SNP analysis of mtDNA, both in the noncoding and coding regions, has been demonstrated using a number of these formats. PMID- 26256812 TI - Phylogenetics and Mitochondrial DNA. AB - Phylogenetic analysis can be conducted using a variety of methods, generally classified as distancebased or character-based approaches. Patterns found through phylogenetic analysis of human mitochondrial DNA (mtDNA) sequences have revealed a wealth of information in such disparate fields as the human evolution; the movement of human lineages throughout history (phylogeography); and the susceptibility of certain groups to devastating diseases. Forensic mtDNA analysis has also benefited from the use of these methods. Phylogenetic assessment of forensic mtDNA databases has revealed a consistency with published data at a depth of analysis that is not attainable with basic population genetic methods. The detailed characteristics of specific sites within a mtDNA sequence are best assessed using phylogenetic methods. These studies have identified the most informative sites for individual differentiation, while also providing quality assurance metrics to apply to individual mtDNA profiles or entire databases. Such a level of evaluation and understanding enhances the interpretation of forensic casework. PMID- 26256813 TI - Naming the Dead - Confronting the Realities of Rapid Identification of Degraded Skeletal Remains. AB - The Armed Forces DNA Identification Laboratory (AFDIL) is one of the leading laboratories in the world for the processing of degraded skeletal remains. Extended efforts have been made to develop protocols and standards that will hold up to the intense scrutiny of both the scientific world and the U.S. legal system. Presented in this paper are the specifics of the in-house systems and procedures that have allowed AFDIL to streamline the processing of degraded skeletal remains and family references for mitochondrial DNA (mtDNA) analysis. These include the development of our in-house bioinformatics systems by which every package and sample that passes through the laboratory is tracked; protocols designed specifically for both questioned and reference samples; and the difficulties inherent in this type of organization. Two case studies presented involve one of ancient remains and one on the recent event of September 11, 2001. Finally, future directions available to both AFDIL and the DNA analysis community as a whole are discussed. PMID- 26256814 TI - Catecholaminergic Polymorphic Ventricular Tachycardia with QT Prolongation. AB - The QT interval in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) is typically normal. However, CPVT patients are sometimes misdiagnosed as concealed long QT syndrome (LQTS), because patients with LQTS also manifest with syncope or sudden death following periods of exertion or extreme emotion. We report a CPVT patient with a pathogenic RyR2 mutation associated with a marked QT prolongation, which normalized after flecainide therapy. PMID- 26256815 TI - The Intersection Between Prevention Science and Evidence-Based Policy: How the SPR Evidence Standards Support Human Services Prevention Programs. AB - The revised Society for Prevention Research (SPR) standards of evidence are an exciting advance in the field of prevention science. We appreciate the committee's vision that the standards represent goals to aspire to rather than a set of benchmarks for where prevention science is currently. The discussion about the standards highlights how much has changed in the field over the last 10 years and as knowledge, theory, and methods continue to advance, the new standards push the field toward increasing rigor and relevance. This commentary discusses how the revised standards support work of translating high-quality evaluations to support evidence-based policy and work supporting evidence-based programs' ability to implement at scale. The commentary ends by raising two areas, generating evidence at scale and transparency of research, as additional areas for consideration in future standards. PMID- 26256817 TI - Evaluating, understanding and improving the quality of clinical placements for undergraduate nurses: A practice development approach. AB - Supervision and support is central to sustainability of clinical placement experiences of undergraduate nurses, but open to influences that impact nurses' capacity to undertake the role. Whilst supervision of learners is integral to the role of health care professionals, the primary responsibility is to deliver safe and effective care. Supervision of learners in practice is impacted by low levels of organisational support, variable individual preparedness, and lack of feedback and recognition for the role from education and industry partners. Over a period of five years the Quality Clinical Placement Evaluation research team, consisting of a partnership between health care and tertiary sectors have developed, and utilised a practice development approach to understand and support the quality of clinical placement for undergraduates and supervising ward nurses involved in Tasmanian clinical placement programs. Importantly, the approach evolved over time to be a flexible three step program supporting the translation of findings to practice, comprised of an education session related to supervision support; survey distribution to undergraduates and supervising ward nurses following clinical placement; and workshops where stakeholders come together to consider findings of the survey, their experience and the local context, with resultant actions for change. This paper reports on findings from the program after successful implementation in urban tertiary hospitals as it was implemented in non-traditional clinical placement settings, including community, aged care and rural settings. Feedback from clinicians identifies the utility of the three step program across these settings. The unique partnerships and approach to evaluating, understanding and improving quality of clinical placements has potential for transferability to other areas, with the value of findings established for all stakeholders. PMID- 26256816 TI - Parameterization of an effective potential for protein-ligand binding from host guest affinity data. AB - Force field accuracy is still one of the "stalemates" in biomolecular modeling. Model systems with high quality experimental data are valuable instruments for the validation and improvement of effective potentials. With respect to protein ligand binding, organic host-guest complexes have long served as models for both experimental and computational studies because of the abundance of binding affinity data available for such systems. Binding affinity data collected for cyclodextrin (CD) inclusion complexes, a popular model for molecular recognition, is potentially a more reliable resource for tuning energy parameters than hydration free energy measurements. Convergence of binding free energy calculations on CD host-guest systems can also be obtained rapidly, thus offering the opportunity to assess the robustness of these parameters. In this work, we demonstrate how implicit solvent parameters can be developed using binding affinity experimental data and the binding energy distribution analysis method (BEDAM) and validated using the Grid Inhomogeneous Solvation Theory analysis. These new solvation parameters were used to study protein-ligand binding in two drug targets against the HIV-1 virus and improved the agreement between the calculated and the experimental binding affinities. This work illustrates how benchmark sets of high quality experimental binding affinity data and physics based binding free energy models can be used to evaluate and optimize force fields for protein-ligand systems. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26256818 TI - Combined Aortic Resection and Stent Graft Insertion for Local Recurrence of Metastatic Lung Carcinoma Following Stereotactic Radiotherapy: A Case Report. AB - Stereotactic radiotherapy (SRT) is a useful treatment for malignant ling tumors. However, SRT is associated with complications such as high local recurrence rate and radiation-induced lung injury. Herein, we report a case of combined aortic resection for after SRT. An 82-year-old man underwent SRT for the metastatic lung carcinoma of rectal cancer at left lower lobe. Three years later, chest computed tomography showed local recurrence at the site of radiotherapy, with suspected invasion of the descending aorta. Thoracotomy was performed after metastatic lung carcinoma interpolation of a stent graft in the descending aorta. Because the tumor firmly adhered to the aorta, left lower lung lobe and aortic wall resection was performed. Pathological findings revealed fibrous hypertrophy and adhesion between the visceral pleura and aorta. As shown in our case, combined aortic resection and stent graft insertion is an effective minimally invasive and safe treatment for SRT-induced tissue damage. PMID- 26256819 TI - Hydrogenation of Graphene by Reaction at High Pressure and High Temperature. AB - The chemical reaction between hydrogen and purely sp(2)-bonded graphene to form graphene's purely sp(3)-bonded analogue, graphane, potentially allows the synthesis of a much wider variety of novel two-dimensional materials by opening a pathway to the application of conventional chemistry methods in graphene. Graphene is currently hydrogenated by exposure to atomic hydrogen in a vacuum, but these methods have not yielded a complete conversion of graphene to graphane, even with graphene exposed to hydrogen on both sides of the lattice. By heating graphene in molecular hydrogen under compression to modest high pressure in a diamond anvil cell (2.6-5.0 GPa), we are able to react graphene with hydrogen and propose a method whereby fully hydrogenated graphane may be synthesized for the first time. PMID- 26256820 TI - Designed, Helical Protein Nanotubes with Variable Diameters from a Single Building Block. AB - Due to their structural and mechanical properties, 1D helical protein assemblies represent highly attractive design targets for biomolecular engineering and protein design. Here we present a designed, tetrameric protein building block, Zn8R4, which assembles via Zn coordination interactions into a series of crystalline, helical nanotubes whose widths can be controlled by solution conditions. X-ray crystallography and transmission electron microscopy (TEM) measurements indicate that all classes of protein nanotubes are constructed through the same 2D arrangement of Zn8R4 tetramers held together by Zn coordination. The mechanical properties of these nanotubes are correlated with their widths. All Zn8R4 nanotubes are found to be highly flexible despite possessing crystalline order, owing to their minimal interbuilding-block interactions mediated solely by metal coordination. PMID- 26256822 TI - Head kinematics during shaking associated with abusive head trauma. AB - Abusive head trauma (AHT) is a potentially fatal result of child abuse but the mechanisms of injury are controversial. To address the hypothesis that shaking alone is sufficient to elicit the injuries observed, effective computational and experimental models are necessary. This paper investigates the use of a coupled rigid-body computational modelling framework to reproduce in vivo shaking kinematics in AHT. A sagittal plane OpenSim computational model of a lamb was developed and used to interpret biomechanical data from in vivo shaking experiments. The acceleration of the head during shaking was used to provide in vivo validation of the associated computational model. Results of this study demonstrated that peak accelerations occurred when the head impacted the torso and produced acceleration magnitudes exceeding 200ms(-)(2). The computational model demonstrated good agreement with the experimental measurements and was shown to be able to reproduce the high accelerations that occur during impact. The biomechanical results obtained with the computational model demonstrate the utility of using a coupled rigid-body modelling framework to describe infant head kinematics in AHT. PMID- 26256821 TI - Joint attention, shared goals, and social bonding. AB - There has recently been interest in the ways in which coordinated movements encourage coactors to feel socially closer to one another, but this has generally overlooked the importance of necessary precursors to this joint action. Here we target two low-level behaviours involved in social coordination that may mediate a relationship between joint actions and social bonding, namely joint attention and shared goals. Participants engaged in a simple reaction time task while sitting next to a partner performing the same task. In a joint attention condition, both participants attended to stimuli presented on the same half of a computer screen, while in a control condition, they attended to opposite sides of the computer screen. Shared goals were manipulated by giving participants the instruction to keep below a threshold score for both individual response times and accuracy (individual goal), or their joint mean response time and accuracy (i.e., averaging their mean response time and accuracy with that of their partner: shared goal). Attending to the same side of the screen led to higher ratings on a composite social bonding index directed towards a partner, while shared goals did not cause any effects on partner ratings. Joint attention was sufficient to encourage social closeness with an interaction partner, which suggests that any activities which encourage attending to the same point in space could have some influence on how connected coactors feel about one another. PMID- 26256823 TI - Neurotoxicity effects of atrazine-induced SH-SY5Y human dopaminergic neuroblastoma cells via microglial activation. AB - Atrazine (2-chloro-4-ethytlamino-6-isopropylamine-1,3,5-triazine; ATR) is a broad spectrum herbicide with a wide range of applications worldwide. However, ATR is neurotoxic; it reduces dopamine levels in the substantia nigra and corpus striatum in the midbrain, affects the absorption of synaptic vesicles and synaptic bodies, and interferes with dopamine storage and uptake in synaptic vesicles, leading to neurodegenerative disorders. Microglia are resident immunocompetent and phagocytic cells that regulate and participate in the microenvironment in the central nervous system. They demonstrate macrophage characteristics after activation by releasing inflammatory cytokines and neurotoxic substances to increase the inflammatory response, and are thus involved in neurodegeneration. The aim of this study was to investigate the neurotoxic effects of ATR-activated microglia-mediated neuronal damage in terms of human dopaminergic neuroblastoma SH-SY5Y cell death. ATR was administered to BV-2 microglial cells at 12.5, 25, and 50 MUM for 1, 6, 12, 24 and 48 h, respectively. ATR increased activated-microglia-induced overexpression of reactive oxygen species, inducible nitric oxide synthase, nitric oxide, gp91(phox), p47(phox), and the inflammatory cytokines tumor necrosis factor alpha and interleukin-1beta, thus reducing SH-SY5Y cell viability. These results suggest that activated microglia may play a critical role in inflammation mediated dopaminergic neuronal death, and provide the basis for further studies on the mechanisms of ATR-induced dopaminergic system toxicity. PMID- 26256824 TI - Photodynamic diagnostic ureterorenoscopy: A valuable tool in the detection of upper urinary tract tumour. AB - BACKGROUND: Photodynamic diagnosis increases the detection rate and hence decreases recurrence rates of urothelial cancer (UC) of the bladder. This technique has been implemented in the upper urinary tract and like in the bladder, has shown to increase the detection rate of urothelial lesions. OBJECTIVES: To determine the sensitivity, specificity, and detection rates for photodynamic diagnostic flexible ureterorenoscopy (PDD-FURS) and white light ureterorenoscopy (WL-FURS). Design between 2009 and 2013, PDD-FURS was performed within 106 Upper urinary tract (UUT) Units (Mean age-72.6+/-9.5). Indications for the procedure included abnormal upper urinary tract on imaging, normal flexible cystoscopy with abnormal urine cytology, endoscopic treatment and follow-up of UUT UC. Oral 5-aminolevulinic acid was used as the photosensitizer administered 3 4 h pre-operatively. RESULTS: 48 lesions were detected, of which 95.8% (46/48) where visualised by PDD-FURS compared to 47.9% (23/48) shown by WL-FURS (P<0.0001). PDD-FURS detected significantly more carcinoma in situ (CIS) or dysplasia lesions than WL-FURS (93.75% (15/16) vs. 18.75% (3/16), respectively, (P=0.0006)). Furthermore, PDD-FURS detected significantly more UC lesions than WL FURS (96.9% (31/32) vs. 62.5% (20/32) (P=0.007)). PDD-FURS was more sensitive (95.8; range: 85.7-99.5) than WL-FURS (53.5; range: 37.7-68.8) in detecting UUT UC (P<0.0001). There was no difference (P=0.716) in the specificity between PDD FURS (96.6; range: 88.1-99.6) and WL-FURS (95.2; range: 86.7-99). CONCLUSIONS: Our results PDD-FURS with oral 5-ALA as photosensitizer suggest higher sensitivity and detection rate of urothelial tumours than WL-FURS, with a good safety profile. In our series, PDD-FURS enhanced the visualisation of flat lesions, such as CIS and dysplasia that otherwise would have been missed. PMID- 26256825 TI - Molecular dynamics investigation of separation of hydrogen sulfide from acidic gas mixtures inside metal-doped graphite micropores. AB - The separation of poisonous compounds from various process fluids has long been highly intractable, motivating the present study on the dynamic separation of H2S in acidic-gas-mixture-filled micropores. The molecular dynamics approach, coupled with the isothermal-isochoric ensemble, was used to model the molecular interactions and adsorption of H2S/CO2/CO/H2O mixtures inside metal-doped graphite slits. Due to the difference in the adsorption characteristics between the two distinct adsorbent materials, the metal dopant in the graphitic micropores leads to competitive adsorption, i.e. the Au and graphite walls compete to capture free adsorbates. The effects of competitive adsorption, coupled with changes in the gas temperature, concentration, constituent ratio and slit width on the constituent separation of mixtures were systematically studied. The molecule-wall binding energies calculated in this work (those of H2S, H2O and CO on Au walls and those of H2O, CO and CO2 on graphite walls) show good agreement with those obtained using density functional theory (DFT) and experimental results. The z-directional self-diffusivities (Dz) for adsorbates inside the slit ranged from 10(-9) to 10(-7) m(2) s(-1) as the temperature was increased from 10 to 500 K. The values are comparable with those for a typical microporous fluid (10(-8)-10(-9) m(2) s(-1) in a condensed phase and 10(-6)-10( 7) m(2) s(-1) in the gaseous state). The formation of H-bonding networks and hydrates of H2S is disadvantageous for the separation of mixtures. The results indicate that H2S can be efficiently separated from acidic gas mixtures onto the Au(111) surface by (i) reducing the mole fraction of H2S and H2O in the mixtures, (ii) raising the gas temperature to the high temperature limit (>=400 K), and (iii) lowering the slit width to below the threshold dimension (<=23.26 A). PMID- 26256826 TI - Analysis of JAK2V617F mutation in Jordanian patients with myeloproliferative neoplasms. AB - OBJECTIVE/BACKGROUND: Myeloproliferative neoplasms (MPNs) are heterogeneous clonal bone marrow stem cell disorders and include polycythemia vera (PV), essential thrombocythemia (ET), and idiopathic myelofibrosis (IMF) neoplasia. In 2005, the JAK2(V617F) mutation was identified in Philadelphia chromosome-negative patients. The aim of this study was to sequence coding exons 12 and 14 of the JAK2 gene in Jordanian patients with MPN. METHODS: Both exons 12 and 14 of the JAK2 gene were amplified using polymerase chain reaction from DNA extracted from 68 blood and bone marrow samples belonging to 57 MPN patients and subjected to DNA sequencing. RESULTS: JAK2(V617F) mutations were detected in 26 of 57 Jordanian patients (45%) with different MPNs. JAK2(V617F) was identified in 70%, 31%, and 14% of PV, ET, and IMF cases, respectively. Five men diagnosed with PV were homozygous for JAK2(V617F), whereas the other 21 patients were heterozygous for the mutation. Neither the JAK2(V617F) mutation nor any DNA polymorphism in exon 12 or exon 14 of the JAK2 gene was detected among the 40 leukemic patients. A rare single nucleotide polymorphism, c.1860C->T (rs375442615), was detected in one patient with ET. CONCLUSION: This study is the first molecular investigation of the JAK2 gene in Jordan. We successfully identified the JAK2(V617F) mutation in Jordanian patients with Philadelphia chromosome-negative MPNs. Our results provide a basis for the early detection of this mutation and simplify the diagnostic workup for these disorders at the molecular level. PMID- 26256827 TI - Cystic clear cell papillary renal cell carcinoma: is it related to multilocular clear cell cystic neoplasm of low malignant potential? AB - AIMS: We report the morphological spectrum of nine cystic clear cell papillary renal cell carcinomas (CCP-RCC). METHODS AND RESULTS: Mean tumour size was 2.1 cm and the stage was pT1a in all cases. The original diagnosis was multilocular clear cell cystic renal neoplasm of low malignant potential (MCCN-LMP) in five and CCP-RCC in four patients. All examples were composed of variably sized cysts lined by one layer of clear cells. Two tumours were exclusively cystic, seven showed tubular formation in the septae and five in which the tubular growth was compact and pseudo-solid. Two tumours had foci of nests and single cells showing similarities to the cellular areas of MCCN-LMP. The tubular/pseudo solid/nested/single-cells foci formed microscopic nodules with a mean size of 1.8 mm. Three tumours had intracystic micropapillary formation. Cells were of International Society of Urological Pathology (ISUP) grades 1-2/4. In all cases, the neoplastic nuclei were aligned away from the basement membranes at least focally. Tumours were positive for paired box gene 8 (PAX8), carbonic anhydrase IX (CAIX), cytokeratin (CK)7 and CK34BE12 and negative for CD10. CONCLUSIONS: Cystic CCP-RCC is a pattern that should be recognized, as it shows overlapping morphological features with both multilocular cyst and MCCN-LMP. This series raises the question of whether some reported MCCN-LMPs are actually cystic CCP RCC. PMID- 26256828 TI - Hip and upper extremity kinematics in youth baseball pitchers. AB - The purpose of this study was to examine the relationship between dynamic hip rotational range of motion and upper extremity kinematics during baseball pitching. Thirty-one youth baseball pitchers (10.87 +/- 0.92 years; 150.03 +/- 5.48 cm; 44.83 +/- 8.04 kg) participated. A strong correlation was found between stance hip rotation and scapular upward rotation at maximum shoulder external rotation (r = 0.531, P = 0.002) and at ball release (r = 0.536, P = 0.002). No statistically significant correlations were found between dynamic hip rotational range of motion and passive hip range of motion. Hip range of motion deficits can constrain pelvis rotation and limit energy generation in the lower extremities. Shoulder pathomechanics can then develop as greater responsibility is placed on the shoulder to generate the energy lost from the proximal segments, increasing risk of upper extremity injury. Additionally, it appears that passive seated measurements of hip range of motion may not accurately reflect the dynamic range of motion of the hips through the progression of the pitch cycle. PMID- 26256829 TI - Bifurcating stents in the pulmonary arteries: A novel technique to relieve bilateral branch pulmonary artery obstruction. AB - Balloon angioplasty and stent placement in close proximity to the bifurcation of the branch pulmonary arteries can be challenging. Multiple approaches have been previously described, though none of these approaches both treats bilateral proximal branch pulmonary artery stenosis and provides an anchor for a transcatheter pulmonary valve replacement. We report a novel approach that involves serial stent placement and balloon dilation through the struts of the stent in each pulmonary artery, along with balloon expansion of the proximal portion of the stents to the diameter of the main pulmonary artery. In the two cases we describe, this strategy resulted in significant relief of branch pulmonary artery obstruction without compromising the anatomy of the main pulmonary artery segment. This technique can be an effective way to alleviate stenoses of the bilateral proximal branch pulmonary arteries and provides a landing zone for a future transcatheter pulmonary valve. PMID- 26256831 TI - Late diagnosis of Takayasu's arteritis with repeated attacks of heart failure and uncontrolled hypertension due to abdominal aortic thrombosis: Case report and review of the literature. AB - Takayasu's arteritis (TA) is a chronic, idiopathic, inflammatory disease affecting the aorta and its branches. To date, only one case involving abdominal aortic thrombosis due to TA has been reported. After bilateral artificial subclavian-iliac bypass, a case of abdominal aortic thrombosis due to TA received a delayed diagnosis in a 44-year-old Chinese male who experienced recurrent episodes of heart failure and uncontrolled hypertension with claudication of two extremities. Abdominal color Doppler sonography and computed tomography aortography (CTA) showed occlusion of the abdominal aorta and bilateral renal artery stenosis. After vascular bypass and during 1 year follow-up, his cardiac function improved and blood pressure was well controlled, with reduced serum creatinine. Postoperative CTA still showed abdominal aortic thrombosis resulting in arterial occlusion extending from the left renal artery initial segment level to the bilateral common iliac artery and the bifurcation of the renal artery, except for the vascular bypass. Abdominal aortic thrombosis due to TA is very rare and potentially life threatening, probably becoming an atherosclerosis risk factor. Doppler sonography and CTA results are important for diagnosis. Artificial vascular bypass can be used for TA in debilitated patients with diffuse aortic disease. PMID- 26256830 TI - Anti-necrotic and cardioprotective effects of a cytosolic renin isoform under ischemia-related conditions. AB - In the heart, secretory renin promotes hypertrophy, apoptosis, necrosis, fibrosis, and cardiac failure through angiotensin generation from angiotensinogen. Thus, inhibitors of the renin-angiotensin system are among the most potent drugs in the treatment of cardiac failure. Renin transcripts have been identified encoding a renin isoform with unknown targets and unknown functions that are localized to the cytosol and mitochondria. We hypothesize that this isoform, in contrast to secretory renin, exerts cardioprotective effects in an angiotensin-independent manner. Cells overexpressing cytosolic renin were generated by transfection or obtained from CX(exon2-9)renin transgenic rats. Overexpression of cytosolic renin reduced the rate of necrosis in H9c2 cardiomyoblasts and in primary cardiomyocytes after glucose depletion. These effects were not mediated by angiotensin generation since an inhibitor of renin activity did not influence the in vitro effects. siRNA-mediated knockdown of endogenous cytosolic renin increased the rate of necrosis and aggravated the pro necrotic effects of glucose depletion. Isolated perfused hearts obtained from transgenic rats overexpressing cytosolic renin exhibited a 50% reduction of infarct size after ischemia-reperfusion injury. Cytosolic renin is essential for survival, both under basal conditions and during glucose starvation. The protective effects are angiotensin-independent and contrary to the known actions of secretory renin. KEY MESSAGES: A cytosolic isoform of renin with unknown functions is expressed in the heart. Cytosolic renin diminishes ischemia induced damage to the heart. The protective effects of cytosolic renin contradict the known function of secretory renin. The effects of cytosolic renin are not mediated via angiotensin generation. Renin-binding protein is a potential target for cytosolic renin. PMID- 26256832 TI - Liver resection after selective internal radiotherapy (SIRT): Proof of concept, initial survival, and safety. AB - BACKGROUND AND OBJECTIVES: Extent of liver resections are restricted by the volume of the future liver remnant. Different strategies have been developed to increase the frequency of curative resections. Selective internal radiation therapy (SIRT) has emerged as an effective therapy for patients with primary non resectable malignancies of the liver. Here, we report the first clinical series of patients with curative liver resection following SIRT. METHODS: Starting 2010, patients with marginally resectable liver metastases treated by SIRT followed by liver resection were identified and prospectively documented in a database for subsequent retrospective analysis. RESULTS: Thirteen patients (five female, eight male; age 70 years [32-77 years]) with marginally resectable liver metastases were selected for liver resection after SIRT. After performing SIRT, 12 patients had potentially curative hepatic resection. In two patients, liver resection after SIRT could not be performed due to the appearance of new extrahepatic metastases. Analyzing the effect of SIRT, we observed a decrease in tumor size with central scaring. None of the patients developed liver necrosis after SIRT. Liver resection was performed safely in all patients. CONCLUSIONS: The combination of SIRT with state-of-the-art liver surgery opens up new therapeutic options in patients with liver metastases. PMID- 26256834 TI - Ancestry, Socioeconomic Status, and Age-Related Cataract in Asians: The Singapore Epidemiology of Eye Diseases Study. AB - PURPOSE: To determine the prevalence of age-related cataract and its ancestral and socioeconomic risk factors in a multi-ethnic Asian population. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A total of 10 033 adults (3353 Chinese, 3280 Malays, and 3400 Indians) aged >40 years in the Singapore Epidemiology of Eye Diseases Study. METHODS: Study participants were invited for a structured interview and received a standardized comprehensive eye examination. Digital lens photographs were taken from eyes of each participant and graded for nuclear, cortical, and posterior subcapsular (PSC) cataract, following the Wisconsin Cataract Grading System. Prevalence data were compared with the Blue Mountains Eye Study (BMES) in Australia. Information on medical and lifestyle factors was collected using questionnaires and blood samples. To increase the precision of racial definition, genetic ancestry was derived from genome-wide single nucleotide polymorphism markers using principal component analysis. Regression models were used to investigate the association of cataract with socioeconomic factors (education and income) and genetic ancestry. MAIN OUTCOME MEASURES: Age-related cataract. RESULTS: A total of 8750 participants (94.0%) had gradable lens photographs. The age-standardized prevalence of cataract surgery in Chinese (16.0%), Malays (10.6%), and Indians (20.2%) was higher than in white subjects (4.1%). We found the age-standardized cataract prevalence in Chinese (30.4%), Malays (37.8%), and Indians (33.1%) was higher than in whites (18.5%). Cataract was 1.5 to 2 times more common in Asians and began 10 years earlier than in white subjects. Malays had significantly higher age-standardized prevalence of nuclear, cortical, and PSC cataract than Chinese (P<0.001). The severity of nuclear, cortical, and PSC cataract was significantly correlated with genetic ancestry in our South East Asian population. Less education and lower income were associated with cataract for Chinese and Indians but not Malays. The presence of visual impairment associated with cataract was higher in people aged >=60 years and Malays. CONCLUSIONS: We showed that people of different Asian ethnicities had a higher prevalence and earlier age of onset of cataract than Europeans. People of Malay ancestry have a greater severity for all cataract subtypes than people of Chinese ancestry. Education and income were associated with cataract for certain Asian subgroups. PMID- 26256833 TI - Degeneration and Regeneration of Subbasal Corneal Nerves after Infectious Keratitis: A Longitudinal In Vivo Confocal Microscopy Study. AB - PURPOSE: To investigate the longitudinal alterations of subbasal corneal nerves in patients with infectious keratitis (IK) during the acute phase, cessation of treatment, and the recovery phase by in vivo confocal microscopy (IVCM). DESIGN: Prospective, longitudinal, case-control, single-center study. PARTICIPANTS: Fifty six eyes of 56 patients with the diagnosis of bacterial (n=28), fungal (n=15), or Acanthamoeba (n=13) keratitis were included in the study. Thirty eyes of 30 normal volunteers constituted the control group. METHODS: Corneal sensation and serial IVCM of the central cornea were performed prospectively using the Heidelberg Retina Tomograph 3/Rostock Cornea Module (Heidelberg Engineering, Heidelberg, Germany). The IVCM images were assessed at 3 time points: at the acute phase (first visit to the cornea service), at cessation of antimicrobial treatment, and up to 6 months after the resolution of infection. MAIN OUTCOME MEASURES: Total nerve number and length, main nerve trunks, branching, and corneal sensation were assessed during the follow-up period. RESULTS: Corneal nerves were reduced significantly during the acute phase in eyes with IK compared with controls across all subgroups, with total nerve length of 5.47+/-0.69 mm/mm2 versus 20.59+/-1.06 mm/mm2 (P<0.0001). At the cessation of treatment, corneal nerves in patients with IK had regenerated, including total nerve length (8.49+/ 0.94 mm/mm2; P=0.02) and nerve branch length (4.80+/-0.37 mm/mm2; P=0.005). During the recovery phase, after resolution of infection, corneal nerves regenerated further, including total nerve length (12.13+/-1.97 mm/mm2; P=0.005), main nerve trunk length (5.80+/-1.00 mm/mm2; P=0.01), and nerve branch length (6.33+/-0.76 mm/mm2; P=0.003) as compared with the acute phase, but were still significantly lower when compared with controls (P<0.05 for all parameters). Corneal degeneration and regeneration correlated with corneal sensation (r=0.47; P=0.0009). CONCLUSIONS: Patients with IK who sustain profound loss of corneal nerves during the acute phase of infection demonstrate increased corneal nerve density during the first 6 months after the resolution of infection. However, despite significant nerve regeneration, corneal nerve density does not recover fully and remains low compared to controls. By providing an objective methodology to monitor corneal re-innervation, IVCM adds potentially important findings that may have implications for clinical management and surgical planning. PMID- 26256835 TI - Participants' views of telephone interviews within a grounded theory study. AB - AIM: To offer a unique contribution to the evolving debate around the use of the telephone during semistructured interview by drawing on interviewees' reflections on telephone interview during a grounded theory study. BACKGROUND: The accepted norm for qualitative interviews is to conduct them face-to-face. It is typical to consider collecting qualitative data via telephone only when face-to-face interview is not possible. During a grounded theory study, exploring users' experiences with overnight mask ventilation for sleep apnoea, the authors selected the telephone to conduct interviews. This article reports participants' views on semistructured interview by telephone. DESIGN: An inductive thematic analysis was conducted on data pertaining to the use of the telephone interview in a grounded theory study. METHODS: The data were collected during 4 months of 2011 and 6 months in 2014. The article presents an inductive thematic analysis of sixteen participants' opinions about telephone interviewing and discusses these in relation to existing literature reporting the use of telephone interviews in grounded theory studies. FINDINGS: Overall, participants reported a positive experience of telephone interviewing. From each participants reports we identified four themes from the data: being 'phone savvy; concentrating on voice instead of your face; easy rapport; and not being judged or feeling inhibited. CONCLUSION: By drawing on these data, we argue that the telephone as a data collection tool in grounded theory research and other qualitative methodologies need not be relegated to second best status. Rather, researchers can consider telephone interview a valuable first choice option. PMID- 26256836 TI - Chirally-modified metal surfaces: energetics of interaction with chiral molecules. AB - Imparting chirality to non-chiral metal surfaces by adsorption of chiral modifiers is a highly promising route to create effective heterogeneously catalyzed processes for the production of enantiopure pharmaceuticals. One of the major current challenges in heterogeneous chiral catalysis is the fundamental level understanding of how such chirally-modified surfaces interact with chiral and prochiral molecules to induce their enantioselective transformations. Herein we report the first direct calorimetric measurement of the adsorption energy of chiral molecules onto well-defined chirally-modified surfaces. Two model modifiers 1-(1-naphthyl)ethylamine and 2-methylbutanoic acid were used to impart chirality to Pt(111) and their interaction with propylene oxide was investigated by means of single-crystal adsorption calorimetry. Differential adsorption energies and absolute surface uptakes were obtained for the R- and S-enantiomers of propylene oxide under clean ultrahigh vacuum conditions. Two types of adsorption behavior were observed for different chiral modifiers, pointing to different mechanisms of imparting chirality to metal surfaces. The results are analyzed and discussed in view of previously reported stereoselectivity of adsorption processes. PMID- 26256837 TI - Determinants and magnitudes of manual force strengths and joint moments during two-handed standing maximal horizontal pushing and pulling. AB - Pushing and pulling are common occupational exertions that are increasingly associated with musculoskeletal complaints. This study focuses on the sensitivity of shoulder capacity to gender, handle height, exertion type (push or pull) and handle orientation for these tasks. All factors except for handle orientation influenced unilateral and total manual force strength (p < 0.01), with exertion type being the most influential. Interaction effects also existed between handle height and exertion type. Additionally, joint moments at the shoulders and low back were influenced by all factors studied (p < 0.01), with exertion type again being most influential. Knowledge of the relative influence of multiple factors on shoulder capacity can provide guidance regarding these factors when designing or evaluating occupational pushing and pulling tasks for a diverse population. Practitioner Summary: pushing and pulling comprise nearly half of all manual materials handling tasks. Practitioners often assess, design or modify these tasks while incorporating constraints, including manual force direction and handle interface. This study provides guidance to aid design of pushing and pulling tasks in the context of shoulder physical capacity. PMID- 26256838 TI - Macrocyclic peptidomimetics with antimicrobial activity: synthesis, bioassay, and molecular modeling studies. AB - Novel, cyclic peptidomimetics were synthesized by facile acylation reactions using benzotriazole chemistry. Microbiological testing of the synthesized compounds revealed an exceptionally high activity against Candida albicans with a minimum inhibitory concentration (MIC) two orders of magnitude lower than the MIC of the antifungal reference drug amphotericin B. A strikingly high activity was also observed against three Gram-negative bacterial strains (Pseudomonas aeruginosa, Klebsiella pneumoniae and Proteus vulgaris), two of which are known human pathogens. Thus the discovered chemotype is a potential polypharmacological agent. The toxicity against mammalian tumor cells was found to be low, as demonstrated in five different human cell lines (HeLa, cervical; PC-3, prostate; MCF-7, breast; HepG2, liver; and HCT-116, colon). The internal consistency of the experimental data was studied using 3D-pharmacophore and 2D-QSAR. PMID- 26256839 TI - Oxidatively Initiated NHC-Catalyzed Enantioselective Synthesis of 3,4 Disubstituted Cyclopentanones from Enals. AB - An unprecedented N-heterocyclic carbene (NHC)-catalyzed annulation of enals to form 3,4-disubstituted cyclopentanones has been discovered. Aryl enals undergo dimerization in the presence of a single-electron oxidant to form C2 symmetric cyclopentanones. A cross-reaction has also been developed, allowing for the synthesis of differentially substituted cyclopentanones. Mechanistically, the reaction is thought to proceed through radical intermediates, further establishing the synthetic utility of this class of reactivity. PMID- 26256842 TI - Common Legal Challenges and Responses in Forensic Breath Alcohol Determination. AB - No other single criminal/civil offense connects the forensic science community together with the legal community more than driving while under the influence of alcohol (DUI). Statutory changes along with political pressure have caused DUI to be a very serious and expensive offense. The result has been an enormous increase in DUI defense challenges in recent years with the primary focus on breath alcohol measurement. This paper addresses several of the more common DUI defense challenges regarding breath alcohol analysis, along with suggested responses. Common DUI defense challenges include: uncertainty in breath alcohol results near statutory limits; interfering substances; storage of alcohol simulator solutions; simulator thermometer uncertainties; instrument repair history; Widmark computations; instrument software; program records; pre-exhalation observation time period; and concurrence between the officer's report and breath alcohol results. Most of these issues are addressed with the prudent construction of administrative rules and employing a forensically sound breath test protocol. PMID- 26256841 TI - Death concerns and psychological well-being in mothers of children with autism spectrum disorder. AB - PURPOSE: Utilizing a terror management theory perspective, the present research examined whether having a child with autism spectrum disorder (ASD) is associated with underlying cognitions and explicit worries about death, and their roles in psychological well-being. METHOD: 147 mothers of children with ASD (n=74) and typically developing children (n=73) completed a fear of death scale, as well as measures of death-thought accessibility, positive and negative affect, depression, and anxiety. RESULTS: Following previous research, mothers of children with ASD reported worse psychological health. Additionally, they evidenced greater death-thought accessibility compared to mothers of typically developing children, but did not differ in explicit worries about mortality. Greater death-thought accessibility, in turn, mediated the influence of ASD diagnosis on negative affect, depression, and anxiety. CONCLUSION: The current study offers an initial understanding of the association between mortality concerns and psychological health for mothers of children with ASD. Further, it underscores the importance of health care providers' efforts to attend to, and educate parents about, their thoughts of mortality, even if the parent does not acknowledge such concerns. WHAT THIS PAPER ADDS: The present study examined the impact of both implicit and explicit worries about death in parents of children with Autism Spectrum Disorder (ASD). Specifically, we were able to demonstrate that increased death-thought accessibility among mothers of children with ASD was associated with worse psychological health. While it is possible for parents of children with ASD to report conscious worries about death, there were no observed differences on this measure. As far as we know, this work is the first to empirically examine the prevalence of mortality-related concerns in this population and the subsequent effects of death-thought accessibility on psychological health. This is an important avenue of research as parents of children with ASD may experience greater worries about leaving their children upon death with no one to care for them, or to leave their children in the care of individuals who may not understand their son or daughter's unique needs. Additionally, the current findings highlight the importance of addressing mortality-related concerns, even when they may not be explicitly recognized, among parents of children with ASD. Given the effectiveness of parent education programs for children with ASD, a primary avenue for intervention may be education. Training care providers in ways to better discuss thoughts of death may help to alleviate stress and foster greater psychological well-being. PMID- 26256843 TI - Conventional and Novel Methods for Facial-Image Identification. AB - This article reviews conventional and novel methods for facial-image identification from forensic aspects. Among the conventional approaches, three methods, i.e., morphological comparison of facial features, anthropometric indices comparison, and face-to-face superimposition, are generally used. The methods most commonly used in caseworks are in the order of morphological comparison, anthropometric indices comparison, and face-to-face superimposition. A novel method based on the superimposition of 2D/3D facial images is introduced and its advantages and disadvantages are described. Assessments of the reliability of facial-image identification, including expert opinions, are discussed. A new retrieval system using a 3D facial-image database is proposed for the screening of suspects' facial images. PMID- 26256844 TI - Mechanisms of Drug Deposition in Hair and Issues for Hair Testing. AB - The purpose of this review is to provide a summary of the knowledge of the mechanisms by which drugs deposit into hair. While much work and many reviews have been produced on methods of analysis of drugs in hair, a smaller body of work and fewer reviews have concentrated on the biochemical mechanisms by which drugs deposit and are retained in hair. Proposed mechanisms are discussed with various studies that have been used to elucidate these mechanisms. While multiple mechanisms are likely involved in the deposition and retention of drugs in hair, melanin and various interactions with melanin including potential covalent linkage of drug with melanin appear to dominate the scheme of interactions. The implications of these interactions are discussed with particular emphasis on the potential difficulties in distinguishing internal deposition from external contamination and the appropriateness of manufacturing control materials. The potential for hair testing to be truly reflective of endogenous deposition may hinge on the ability to isolate and analyze melanin adducts of drugs that would be indicative of endogenous drug deposition during hair growth and active melanogenesis. PMID- 26256845 TI - Objective Diagnosis of Drowning by the "Diatom Test" - A Critical Review. AB - The identification of diatoms in the body tissues to prove a death by drowning (known as the diatom test) dates back to the end of the 19th century. However, in recent decades the reliability of this method was disproved because of an alleged inaccuracy and high false positive rate; nonetheless, the matter is still highly controversial. The purpose of the present work is to offer a critical review of the subject with a specific emphasis on the technical problems. In particular, contamination of samples during autopsy and of tissue extracts during processing was recognized as the main source of false positive results. However, the possibility of diatom passive penetration into the body (particularly into lungs) during submersion cannot be excluded, especially in highly transformed cadavers. Hence, tissues that are highly secluded from the drowning medium, such as bone marrow, are preferred as samples, according to the most recent literature. Additional information on the drowning site and circumstances can be drawn from the qualitative and quantitative comparison between the diatoms found in the body tissues and those present in the drowning water. From the analytical point of view, the majority of authors digest tissues by treatment with strong acids, often after oxidation; alternatively, proteolytic enzymes are widely used. Detection is generally carried out by light microscopy, but scanning electron microscopy (SEM) shows much better resolution, which is important for the identification of the smallest diatoms or diatom fragments. In the experimental part of the work, a recent evolution of SEM, known as environmental scanning electron microscopy (ESEM) has been tested on drowning victims. The main feature of ESEM is the possibility to work on standard microscopic preparations without the need of sample coating, which allows switching between light and electron microscopy, thus taking advantage of the wide optical field of the former technique and of the high resolution of the latter. On this basis, we propose an integrated approach to the diatom test including a screening with light microscopy (200-400*) and a confirmation with ESEM (5,000-20,000*). The review includes 92 references. PMID- 26256846 TI - Charting the known chemical space for non-aqueous lithium-air battery electrolyte solvents. AB - Li-air batteries are very promising candidates for powering future mobility, but finding a suitable electrolyte solvent for this technology turned out to be a major problem. We present a systematic computational investigation of the known chemical space for possible Li-air electrolyte solvents. It is shown that the problem of finding better Li-air electrolyte solvents is not only - as previously suggested - about maximizing Li(+) and O2(-) solubilities, but also about finding the optimal balance of these solubilities with the viscosity of the solvent. As our results also show that trial-and-error experiments on known chemicals are unlikely to succeed, full chemical sub-spaces for the most promising compound classes are investigated, and suggestions are made for further experiments. The proposed screening approach is transferable and robust and can readily be applied to optimize electrolytes for other electrochemical devices. It goes beyond the current state-of-the-art both in width (considering the number of compounds screened and the way they are selected), as well as depth (considering the number and complexity of properties included). PMID- 26256847 TI - Physicochemical Approach to Determine the Mechanism for Acid-Base Disorders in 793 Hospitalized Foals. AB - BACKGROUND: The quantitative effect of strong electrolytes, unmeasured strong anions (UAs), pCO2, and plasma protein concentrations in determining plasma pH can be demonstrated using the physicochemical approach. Plasma anion gap (AG) and strong ion gap (SIG) are used to assess UAs in different species. HYPOTHESES: Strong ions are a major factor influencing changes in plasma pH of hospitalized foals. AG and SIG accurately predict severe hyper-L-lactatemia ([L-lac(-)] > 7 mmol/L). ANIMALS: Seven hundred and ninety three hospitalized foals < 7 days old. METHODS: Retrospective study. The relationship between measured pH and physicochemical variables, and the relationship between plasma [L-lac(-)] and AG and SIG, were determined using regression analyses. Optimal AG and SIG cut points to predict hyper-L-lactatemia were identified using an ROC curve analysis. RESULTS: Combined, the measured strong ion difference and SIG accounted for 54 69% of the changes in the measured arterial pH of hospitalized foals. AG and SIG were significantly associated with plasma [L-lac(-)] (P < .0001). The receiver operator characteristics (ROC) AUC of AG and SIG for prediction of severe hyper-L lactatemia were 0.89 (95%CI, 0.8-0.95; P < .0001) and 0.90 (95%CI, 0.81-0.96; P < .0001), respectively. Severe hyper-L-lactatemia was best predicted by AG > 27 mmol/L (sensitivity 80%, 95%CI, 56-94, specificity 85%, 95%CI, 73-93; P < .0001) and SIG <-15 mmol/L (sensitivity 90%, 95%CI, 68-98; specificity 80%; 95%CI, 68 90; P < .0001). CONCLUSION AND CLINICAL RELEVANCE: Altered concentrations of strong ions (Na(+), K(+), Cl(-)) and UAs were the primary cause of acidemia of hospitalized foals. AG and SIG were good predictors of hyper-L-lactatemia and could be used as surrogate tests. PMID- 26256849 TI - HemX is required for production of 2-ketogluconate, the predominant organic anion required for inorganic phosphate solubilization by Burkholderia sp. Ha185. AB - The bacterium Burkholderia sp. Ha185 readily solubilizes inorganic phosphate by releasing the low molecular weight organic anion, 2-ketogluconate. Using random transposon mutagenesis and in silico analysis, a mutation that caused almost complete abolition of phosphate solubilization was located within hemX, which is part of the hem operon. Burkholderia sp. Ha185 HemX is a multidomain protein, predicted to encode a bifunctional uroporphyrinogen-III synthetase/uroporphyrin III C-methyltransferase, which has not previously been implicated in phosphate solubilization. Complementation of hemX restored the ability of the mutant to solubilize phosphate in both plate and liquid cultures. Based on a combination of organic-anion profiling, quantitative polymerase chain reaction and in silico analyses, hemX was confirmed to be solely responsible for hydroxyapatite solubilization in Burkholderia sp. Ha185. It is proposed that the biosynthesis of a yet to be determined redox cofactor by HemX is the main pathway for generating 2-ketogluconate via a haem-dependent gluconate 2-dehydrogenase in Burkholderia sp. Ha185. PMID- 26256848 TI - High respiratory rate is associated with early reduction of lung edema clearance in an experimental model of ARDS. AB - BACKGROUND: The independent impact of respiratory rate on ventilator-induced lung injury has not been fully elucidated. The aim of this study was to investigate the effects of two clinically relevant respiratory rates on early ventilator induced lung injury evolution and lung edema during the protective ARDSNet strategy. We hypothesized that the use of a higher respiratory rate during a protective ARDSNet ventilation strategy increases lung inflammation and, in addition, lung edema associated to strain-induced activation of transforming growth factor beta (TGF-beta) in the lung epithelium. METHODS: Twelve healthy piglets were submitted to a two-hit lung injury model and randomized into two groups: LRR (20 breaths/min) and HRR (40 breaths/min). They were mechanically ventilated during 6 h according to the ARDSNet strategy. We assessed respiratory mechanics, hemodynamics, and extravascular lung water (EVLW). At the end of the experiment, the lungs were excised and wet/dry ratio, TGF-beta pathway markers, regional histology, and cytokines were evaluated. RESULTS: No differences in oxygenation, PaCO2 levels, systemic and pulmonary arterial pressures were observed during the study. Respiratory system compliance and mean airway pressure were lower in LRR group. A decrease in EVLW over time occurred only in the LRR group (P < 0.05). Wet/dry ratio was higher in the HRR group (P < 0.05), as well as TGF-beta pathway activation. Histological findings suggestive of inflammation and inflammatory tissue cytokines were higher in LRR. CONCLUSION: HRR was associated with more pulmonary edema and higher activation of the TGF-beta pathway. In contrast with our hypothesis, HRR was associated with less lung inflammation. PMID- 26256850 TI - Role of temperature in the recombination reaction on dye-sensitized solar cells. AB - The performance of photovoltaic (PV) devices as a function of temperature is crucial for technical development and for accurate commercial information. Along with solar irradiance, temperature is the most important operating factor of the PV device performance. Normally, it is widely accepted that dye sensitized solar cells (DSC) show minimal energy efficiency dependence with temperature (20-60 degrees C). The energy efficiency in DSCs depends on the light absorption, charge transport (ohmic resistances) and recombination rates. In this study, the recombination reaction kinetics was studied within a wide temperature range. A unique laser assisted sealing technique that allows studying the temperature effect between -5 degrees C and 105 degrees C without electrolyte leakage or external contamination was used. To the best of our knowledge, this is the highest operating temperature ever considered in kinetic studies of liquid state DSCs. The electrochemical reaction between electrons and triiodide/iodide ions was shown to be the most important factor for determining the energy efficiency of DSCs as a function of temperature. It was concluded that the activation energy of the recombination reactions depends on the interface where it happens - TiO2/electrolyte and SnO2-F/electrolyte - and on the temperature. It was found that in addition to temperature having a deep influence on the recombination reaction rate, the energy of the injecting electron is also critical. These conclusions should provide solid ground for further developments in the DSCs and perovskite solar cells, and allow a better comparison of the energy efficiency of different PV technologies over a range of operating temperatures. PMID- 26256851 TI - Is there a role for axillary reverse mapping in the current management of breast cancer treatment? PMID- 26256852 TI - Research: a viable and meaningful career alternative for occupational therapists. PMID- 26256853 TI - Secondary health conditions experienced by people with spinal cord injury within community living: implications for a National Disability Insurance Scheme. AB - BACKGROUND: Australia's National Disability Insurance Scheme (NDIS) provides supports for individuals, delivered through a personalised participant planning process, to influence choice and goal attainment. AIM: This study aimed to use both quantitative and qualitative methods to examine the impact of secondary health conditions on the experiences of people with spinal cord injury (SCI) who have returned to community living, in the context of Australia's National Disability Strategy and recently launched NDIS. Exploration of lived experience of health conditions following SCI utilising this mixed methods approach may offer important insights for effective planning within an NDIS. METHODS: A cross sectional survey using the Spinal Cord Injury Secondary Conditions Scale (SCISCS), demographic questionnaire and in-depth interview was undertaken with 33 people with SCI living in the community. Demographic and SCISCS data were reported using descriptive statistics. Interviews were audio-taped, transcribed and analysed thematically. RESULTS: Participants were on average 58.5 years of age and 20 years post-injury. Five key themes emerged relating to (i) spasm and pain; (ii) sexual dysfunction; (iii) pressure areas; (iv) fatigue; and (v) the impact of secondary health conditions on life role participation and choice of supports and equipment. CONCLUSION: Secondary health conditions can significantly impact occupational participation following SCI. Appropriate intervention, including customised equipment and direct support, if delivered as part of an effective NDIS, may prevent or reduce the severity of these conditions and offer the potential to influence health and participation outcomes of people who have returned to community living. PMID- 26256854 TI - Feedback on students' clinical reasoning skills during fieldwork education. AB - BACKGROUND/AIM: Feedback on clinical reasoning skills during fieldwork education is regarded as vital in occupational therapy students' professional development. The nature of supervisors' feedback however, could be confirmative and/or corrective and corrective feedback could be with or without suggestions on how to improve. The aim of the study was to evaluate the impact of supervisors' feedback on final-year occupational therapy students' clinical reasoning skills through comparing the nature of feedback with the students' subsequent clinical reasoning ability. METHOD: A mixed-method approach with a convergent parallel design was used combining the collection and analysis of qualitative and quantitative data. From focus groups and interviews with students, data were collected and analysed qualitatively to determine how the students experienced the feedback they received from their supervisors. By quantitatively comparing the final practical exam grades with the nature of the feedback, their fieldwork End-of-Term grades and average academic performance it became possible to merge the results for comparison and interpretation. RESULTS: Students' clinical reasoning skills seem to be improved through corrective feedback if accompanied by suggestions on how to improve, irrespective of their average academic performance. Supervisors were inclined to underrate high performing students and overrate lower performing students. CONCLUSIONS: Students who obtained higher grades in the final practical examinations received more corrective feedback with suggestions on how to improve from their supervisors. Confirmative feedback alone may not be sufficient for improving the clinical reasoning skills of students. PMID- 26256855 TI - Cognitive interventions and exercise-based interventions seem to show promise for supporting mobility for community-dwelling older adults, where educational interventions have mixed evidence. PMID- 26256856 TI - Emerging evidence for the benefits of support programmes and environments which support walking, for older adults community mobility, however, inconclusive evidence for the effectiveness of licensing policy intervention. PMID- 26256858 TI - Magnetic anomalies and itinerant character of electrochemically Li-inserted Li[Li1/3Ti5/3]O4. AB - Spinel oxides of Li[LiyTi2-y]O4 with 0 <=y<= 1/3 exhibit two desirable features for solid state chemistry and condensed matter physics. One is a reversible lithium insertion/extraction reaction, in particular for Li[Li1/3Ti5/3]O4, and the other is a superconducting transition at Tc? 13 K for Li[Ti2]O4. To study the change in magnetic environments of the y = 1/3 compound with excess Li(x), we measured the magnetic susceptibility (chi) for the Li1+x[Li1/3Ti5/3]O4 samples with 0 <=x<= 0.95, which were prepared by an electrochemical Li insertion reaction into Li[Li1/3Ti5/3]O4. Even for the x = 0 sample, two magnetic anomalies were found at T (=63 K) and T (=21 K), despite the fact that all Ti ions should be in the 4+ state with S = 0. A comparative study of TiO2 and Li2TiO3 revealed that these magnetic anomalies are not impurity-induced effects but are caused by an intrinsic nature of Li[Li1/3Ti5/3]O4, probably due to either slight compositional deviation from stoichiometry or dislocations such as a Magneli phase. For the x > 0 samples, the chi vs. temperature curve was found to consist of a temperature-independent Pauli-paramagnetic contribution and a Curie-Weiss contribution. Detailed analyses of chi clarified the systematic variations of the effective magnetic moment of Ti ions, effective mass of electrons in the conduction band, and density of states at the Fermi level with x, indicating that the Li(+) ions at the 16d site play a significant role in localizing d electrons of Ti(3+) ions. PMID- 26256859 TI - Prostate cancer: AR splice variant dimerization-clinical implications. PMID- 26256860 TI - Novel methods for mapping the cavernous nerves during radical prostatectomy. AB - The cavernous nerves, which course along the surface of the prostate gland, are responsible for erectile function. During radical prostatectomy, urologists are challenged in preserving these nerves and their function. Cavernous nerves are microscopic and show variable location in different patients; therefore, postoperative sexual potency rates are widely variable following radical prostatectomy. A variety of technologies, including electrical and optical nerve stimulation, dye-based optical fluorescence and microscopy, spectroscopy, ultrasound and magnetic resonance imaging have all been used to study cavernous nerve anatomy and physiology, and some of these methods are also potential intraoperative methods for identifying and preserving cavernous nerves. However, all of these technologies have inherent limitations, including slow or inconsistent nerve responses, poor image resolution, shallow image depth, slow image acquisition times and/or safety concerns. New and emerging technologies, as well as multimodal approaches combining existing methods, hold promise for improved postoperative sexual outcomes and patient quality of life following radical prostatectomy. PMID- 26256861 TI - Interaction of propofol with voltage-gated human Kv1.5 channel through specific amino acids within the pore region. AB - The intravenous anesthetic propofol affects the function of a diversity of ligand gated and voltage-gated ion channels. However, there is little information as to whether propofol directly interacts with voltage-gated ion channel proteins to modulate their functions. The Kv1.5 channel is activated by membrane depolarization during action potentials and contributes to atrial repolarization in the human heart. This study was undertaken to examine the effect of propofol on voltage-gated human Kv1.5 (hKv1.5) channel and to elucidate the underlying molecular determinants. Site-directed mutagenesis was carried out through six amino acids that reside within the pore domain of hKv1.5 channel. Whole-cell patch-clamp technique was used to record membrane currents through the wild type and mutant hKv1.5 channels heterologously expressed in Chinese hamster ovary cells. Propofol (>=5 MUM) reversibly and concentration-dependently (IC50 of 49.3+/-9.4 MUM; n=6) blocked hKv1.5 current. Propofol-induced block of hKv1.5 current gradually progressed during depolarizing voltage-clamp steps and was enhanced by higher frequency of activation, consistent with a preferential block of the channels in their open state. The degree of current block by propofol was significantly attenuated in T480A, I502A, I508A and V516A, but not in H463C and L510A mutants of hKv1.5 channel. Thus, several amino acids near the selectivity filter (Thr480) or within S6 (Ile502, Ile508 and Val516) are found to be critically involved in the blocking action of propofol. This study provides the first evidence suggesting that direct interaction with specific amino acids underlies the blocking action of propofol on voltage-gated hKv1.5 channel. PMID- 26256863 TI - Social participation experiences of mothers of children with cerebral palsy in an Iranian context. AB - BACKGROUND/AIM: Social participation is increasingly of interest in research that investigates the impact of caring for a child with a disability. Little has been investigated about the social participation experiences of mothers of children with cerebral palsy (CP). This study explored social participation among Iranian mothers of children with CP. METHODS: The conventional qualitative content analysis method was utilised. Data were collected via in-depth semi-structured interviews with 14 mothers (aged 26-45 years) of children with CP with the gross motor function classification system expanded & revised levels III-V. Constant comparative analysis was deployed for data analysis. RESULTS: The results were identified and classified into three main themes: (i) polarisation of positive and negative feelings; (ii) challenges to mothers' social activity; and (iii) striving to engage in society. CONCLUSION: In the Iranian context, mothers of children with CP are facing many challenges to social participation and seem to have been neglected by the health-care system. One of the priorities of Iranian health policy makers may be developing, establishing and implementing social support to enable the mothers to participate in social activities. Furthermore, occupational therapists can contribute and guide mothers' social participation by creating programs to develop and utilise skills for them. PMID- 26256864 TI - [Picture in Clinical Hematology]. PMID- 26256865 TI - [Impacts of iron overload on hematopoiesis and its microenvironment]. AB - A significant number of reports have described hematopoietic improvement after iron chelation therapy in iron-overloaded (IO) patients. These observations indicate negative impacts of excess iron on hematopoiesis. To investigate how excess iron affects hematopoiesis, we generated IO mice and examined hematopoietic parameters in these mice. IO mice did not show significant defects in the hematopoietic data of peripheral blood. Myeloid progenitor cells in the bone marrow were increased in IO mice, but the number and function of the erythroid progenitors and hematopoietic stem cells were not significantly affected. However, bone marrow transplantation from normal donors to IO recipients showed delayed hematopoietic reconstitution. Quantitative RT-PCR analyses of the bone marrow stromal cells demonstrated remarkably reduced expressions of several important cytokines, e.g. CXCL12, VCAM-1, Kit-ligand and IGF-1, in the IO mice. In addition, erythropoietin and thrombopoietin levels were significantly suppressed, and oxidative stress was significantly increased in the IO bone marrow and liver. Our findings thus indicate that excess iron can damage bone marrow stromal cells and other vital organs that support hematopoiesis, presumably via increased oxidative stress. PMID- 26256866 TI - [In vivo imaging of intracellular signaling molecules: Come/Stop signals of neutrophils during acute inflammation]. AB - Many chemical mediators regulate neutrophil recruitment to inflammatory sites. Although the actions of each of these chemical mediators have been demonstrated with neutrophils in vitro, how they act cooperatively or counteract each other in vivo remains largely unknown. To understand the behaviors of neutrophils in vivo, the activities of intracellular signaling molecules must be visualized in living tissues. For this purpose, we can use genetically-encoded biosensors based on the principle of Forster resonance energy transfer (FRET). In this review, we first provide an overview of FRET biosensors and then describe how we can utilize these biosensors to visualize the activity changes of signaling molecules in neutrophils during extravasation. In relation to this topic, we will also describe the development of transgenic mice expressing the FRET biosensors and in vivo two-photon excitation microscopy. PMID- 26256867 TI - [Intravital multiphoton imaging of live bone tissues revealing hematopoietic cell dynamics in vivo]. AB - During the last decade, multiphoton fluorescent microscopy has launched a new era in the field of biology. By using this advanced imaging technique we have established a system for visualizing the in situ behaviors of a diversity of living cells within intact tissues and organs. Among them we succeeded in visualizing the various dynamic phenomena within bones, a mysterious organ wherein various hematopoietic and immune cells are produced and functioning. However, these cell types are poorly understood with conventional methodologies such as histological analyses of decalcified bone sections. We have thus far focused on the behavior of osteoclasts, a type of specialized macrophage contributing to physiological turnover of bone tissues as well as pathological bone destruction, and have revealed novel mechanisms controlling the migration and function of osteoclasts in situ. Functional coupling between bone-destroying osteoclasts and bone-replenishing osteoblasts could also be visualized demonstrating a genuine mode of 'cross-talk' among these cell types. Furthermore, we have recently imaged in situ behaviors of different hematopoietic cells in bone marrow. Herein we present our latest data on cellular dynamics in the bone cavity, and discuss the applications of this novel methodology for future studies in the field of hematology. PMID- 26256862 TI - The role of inflammation in suicidal behaviour. AB - OBJECTIVE: Over the past decade, clinical data have accumulated showing that inflammation might contribute to the pathophysiology of suicide. To evaluate the associations and to identify the support for pathways linking inflammatory processes with suicidal behaviour, a comprehensive review of the literature was undertaken. METHOD: The search terms 'cytokine', 'risk factors', 'kynurenine', 'asthma', 'allergy', 'autoimmunity', 'traumatic brain injury', 'infection' along with the terms 'inflammation' and 'suicide' were entered into PubMed, and a thorough analysis of the publications and their reference lists was performed. RESULTS: The effects of inflammation on mood and behaviour could partially be mediated by kynurenine pathway metabolites, modulating neuroinflammation and glutamate neurotransmission. At the same time, the triggers of the inflammatory changes documented in suicidal patients may be attributed to diverse mechanisms such as autoimmunity, neurotropic pathogens, stress or traumatic brain injury. CONCLUSION: Targeting the inflammatory system might provide novel therapeutic approaches as well as potential biomarkers to identify patients at increased risk. For the goal of improved detection and treatment of suicidal individuals to be achieved, we need to develop a detailed understanding of the origin, mechanisms and outcomes of inflammation in suicidal behaviour. PMID- 26256868 TI - [Roles of mTOR signalings in hematopoiesis and leukemogenesis]. AB - Mechanistic/mammalian target protein of rapamycin (mTOR) is an evolutionarily conserved kinase that plays a critical role in sensing and responding to growth factors, cytokines and nutrients, including amino acids and glucose. Although mTOR was originally discovered as a target protein of rapamycin, the inhibitory effects of rapamycin on mTORC1 substrates are complex. Recent studies using genetic approaches have clearly demonstrated the physiological roles of mTOR complexes in regulating the maintenance of hematopoietic and leukemia stem cells. Advances in understanding of how mTOR signaling is involved in mechanisms of normal hematopoiesis and leukemogenesis may lead to novel therapeutic approaches that can successfully eradicate leukemia. PMID- 26256869 TI - [Distinct vascular niches determine hematopoietic stem cell fate]. AB - Identification of cellular constituents of the hematopoietic stem cell (HSC) niche has recently been the subject of intensive investigation. To investigate the spatial localization of the HSC niches in bone marrow, we have established a whole-mount immunofluorescence imaging technique in which the 3D spatial relationships between stromal structures and HSCs in the BM can be precisely determined. The imaging assessment combined with computational simulations has uncovered a significant association between HSCs and arterioles, ensheathed exclusively by rare Nestin(bright) NG2+ pericytes (Nes(peri) cells), distinct from sinusoid-associated Nestin(dim) Leptin receptor (LepR)+ (Nes(retic)) cells which reportedly represent peri-vascular niche cells. Depletion of NG2+ cells using NG2-creERTM / inducible diphtheria toxin receptor (iDTR) mice changed HSC localization away from arterioles, induced HSC cycling and reduced long-term repopulation of HSCs in BM, suggesting that periarteriolar NG2+ cells form quiescent niches for HSCs. These results form the basis of studies that will allow us to genetically dissect the functions of distinct vascular niches. This vascular niche model, in which arterioles and sinusoids differentially regulate HSC quiescence and proliferation, respectively, have implications for the behavior of healthy HSC and may be useful in the future for evaluating the niches for cancer (leukemic) stem cells. PMID- 26256870 TI - [Genetic and epigenetic abnormalities in myeloproliferative neoplasms]. AB - Mutations in JAK2, MPL and CALR are regarded as driver mutations, and are mutually exclusively detected in more than 90% of myeloproliferative neoplasms (MPNs). In addition, mutations in epigenetic regulator genes such as TET2 or DNMT3A are detected in MPNs. Although the roles of mutations in epigenetic regulator genes were clarified in normal hematopoiesis, their roles have remained unclear in malignant hematopoiesis of MPNs. We analyzed three lines of mutant mice: mice with JAK2V617F, a representative of driver gene mutations; mice with loss of TET2, a representative of epigenetic abnormalities; and mice with both. We thereby clarified two roles of loss of TET2 in malignant hematopoiesis of JAK2 mutated MPNs: one is "disease initiator and sustainer" via reinforcing the function of JAK2-mutated hematopoietic stem cells, and the other is "disease accelerator". New strategies in risk assessment or treatment are required, considering not only single but also multiple mutations. PMID- 26256871 TI - [New hemophilia treatment employing a bispecific antibody to factors IXa and X]. AB - Unmet needs of current hemophilia A treatment include the requirement for frequent intravenous infusions, inhibitor development, and containment of high medical costs. In order to overcome these issues, we produced FVIII which mimics a bispecific antibody against FIXa/FX. ACE910 demonstrated hemostatic effects on both ongoing and spontaneous joint bleeding in the primate acquired hemophilia A model. Recently, a phase 1 study for PK, PD, and the safety of ACE910 was initiated. The t1/2 was approximately 30 days. There were no severe ACE910 related adverse events. Furthermore, bleeding was remarkably decreased by weekly subcutaneous administration in patients with severe hemophilia A, regardless of whether an inhibitor was used. ACE910 has the remarkable advantages of prophylactic efficacy which can be achieved by convenient subcutaneous administrations at a markedly reduced frequency. PMID- 26256872 TI - [Antithrombin resistance: a new mechanism of inherited thrombophilia]. AB - Venous thromboembolism is a multifactorial disease resulting from complex interactions among genetic and environmental factors. To date, numerous genetic defects have been found in families with hereditary thrombophilia, but there may still be many undiscovered causative gene mutations. We investigated a possible causative gene defect in a large Japanese family with inherited thrombophilia, and found a novel missense mutation in the prothrombin gene (p.Arg596Leu) resulting in a variant prothrombin (prothrombin Yukuhashi). The mutant prothrombin had moderately lower activity than wild type prothrombin in clotting assays, but formation of the thrombin-antithrombin (TAT) complex was substantially impaired resulting in prolonged thrombin activity. A thrombin generation assay revealed that the peak activity of the mutant prothrombin was fairly low, but its inactivation was extremely slow in reconstituted plasma. The Leu596 substitution caused a gain-of-function mutation in the prothrombin gene, resulting in resistance to antithrombin and susceptibility to thrombosis. We also showed the effects of the prothrombin Yukuhashi mutation on the thrombomodulin protein C anticoagulation system, recent development of a laboratory test detecting antithrombin resistance in plasma, and another antithrombin resistant mutation found in other thrombophilia families. PMID- 26256873 TI - [Development of new treatments for extranodal NK/T-cell lymphoma in Japan]. AB - Extranodal NK/T-cell lymphoma, nasal type (ENKL), accounts for less than 3% of malignant lymphomas in Japan. Based on the results of prospective clinical trials, ENKL treatment has dramatically improved during the last decade in Japan. The Lymphoma Study Group of the Japan Clinical Oncology Group (JCOG) conducted a phase I/II study (JCOG0211) of concurrent chemoradiotherapy for newly-diagnosed, localized ENKL. The trial showed an excellent 5-year overall survival rate (70%) and acceptable toxicity of RT-2/3DeVIC. The NK-cell Tumor Study Group in Japan, together with Asian collaborators, conducted clinical trials (SMILE-PI & PII) of SMILE chemotherapy for patients with newly-diagnosed stage IV, or relapsed/refractory ENKL. The overall response rate for 2 cycles of SMILE in 38 evaluated patients was 79%. The 2013 Japanese Society of Hematology guidelines recommend RT-2/3DeVIC for the treatment of newly-diagnosed ENKL of stage IE and contiguous stage IIE with cervical node involvement. For other ENKL, SMILE or other L-asparaginase-containing chemotherapies are recommended. A large retrospective study evaluating the efficacy and toxicity of these new treatments in clinical practice is currently underway in Japan. Close cooperation between radiation oncologists and international collaboration will be the key factors in developing better first-line treatments for ENKL. PMID- 26256874 TI - [Recent progress of diagnosis and treatment in NK cell neoplasms]. AB - Aggressive natural killer cell leukemia (ANKL) is a malignant disorder of mature NK cells that is relatively common in East Asia. It is associated with Epstein Barr virus in more than 80% of patients. The median survival is not more than three months after diagnosis. In a recent survey of 34 cases with ANKL, the median patient age was 40 years and the age distribution followed a bimodal pattern. Morphologically, the ANKL cells varied from large granular lymphocytes to atypical cells with pleomorphic-like appearances. Clinical characteristics include fever, liver dysfunction, hemophagocytic syndrome, and a rapidly progressive course. In one third of patients, tumor cells in peripheral blood or the bone marrow are below 20% at initial presentation, which might lead to diagnostic delay. L-asparaginase-based chemotherapy plus allogeneic hematopoietic stem cell transplantation (HSCT) is a potential therapeutic option with curative intent. As for extranodal NK/T cell lymphoma, nasal type, HSCT could be anticipated to provide survival benefit or a chance of cure for patients in clinical stage II to IV with complete remission at transplantation. However, the optimal stem cell source, timing of transplantation, and preconditioning regimen require further elucidation. PMID- 26256875 TI - [TET2 as a gatekeeper for hematologic malignancies]. AB - TET (Ten Eleven Translocation) family proteins are dioxygenases that convert methylcytosine to hydroxymethylcytosine, and play an important role in the DNA demethylation process. Most notably, TET2 mutations have frequently been identified in myeloid malignancies, such as myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), chronic myelomonocytic leukemia, and acute myeloid leukemias, as well as angioimmunoblastic T-cell lymphoma and a proportion of peripheral T-cell lymphomas. To date, various types of Tet2 knockout/knockdown mice have been generated. Tet2 mutations induce enhanced self-renewal ability and competitive repopulation capacity in hematopoietic stem cells, and various MPN/MDS-like diseases and T-cell lymphoma consequently develop in model mice. These findings appear to have a strong correlation with the recently identified TET2 mutations in a significant proportion of healthy elderly people, and suggest that TET2 mutations lead to a pre-cancer state in hematopoietic stem/progenitor cells. In conclusion, TET2 might play a major role as a gate keeper for hematopoietic stem/progenitor cells preventing them from developing into various hematologic malignancies by acquiring additional disease-specific gene mutations. PMID- 26256876 TI - [Functional analysis of TET2 using a knockdown mouse model]. AB - In myeloid malignancies, mutations have occurred in epigenetic regulator genes, including Ten-Eleven-Translocation 2 (TET2). TET2 is an enzyme that catalyzes the conversion of 5-methylcytosine into 5-hydroxymethylcytosine (5-hmC) which is a key intermediate for oxidative DNA demethylation. We analyzed the in vivo phenotype of TET2 failure using Ayu17-449 (TET2(trap/trap)) mice created by the gene-trap method in which TET2 mRNA levels were decreased to about 20% of the level in wild-type (WT) mice. In TET2(trap/trap) mice the levels of 5-hmC in genomic DNA from bone marrow (BM) cells were decreased in comparison to WT mice. TET2(trap/trap) mice were born at an expected Mendelian frequency but died at a high rate by postnatal day 3, indicating TET2 to be essential for survival. In analysis of the hematopoietic system, transplantation of TET2(trap/trap), but not WT fetal liver cells, led to mild myeloid hyperplasia and splenomegaly in WT recipient mice, but no onsets of lethal hematological malignancies were observed during a follow-up period of 12 months. TET2 knockdown led to an increased serial replating capacity of BM cells in vitro and increased hematopoietic stem cell (HSC) self-renewal in vivo in competitive repopulation and serial transplantation assays. These data indicate that TET2 has a critical role in survival and HSC homeostasis. PMID- 26256877 TI - [A survey of HTLV-1 carrier clinics in Japan]. AB - Human T-lymphotropic virus type-I (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma and HTLV-1 associated myelopathy/tropical spastic paraparesis. Currently, mother-to-child transmission via breastfeeding and sexual intercourse are considered to be the two major routes for HTLV-1 infection. We surveyed four clinics in Japan (two HTLV-1 carrier clinics in non-endemic areas and one in an endemic area, and one hematology clinic in a highly endemic area) and reviewed the management of carriers. In HTLV-1 carrier clinics, more than half of visitors had learned of their infections based on an examination conducted either for blood donation or pregnancy. Although half of visitors had known of their infection more than 2 years prior to their visit, they became to visit the clinics probably due to recent awareness of HTLV-1 in public and of carrier clinics. They requested a detailed explanation, and check-ups for infection and its related diseases. In contrast, most visitors in highly endemic areas had apparently received good explanations from their primary care physicians. It is noteworthy that neither parent of more than half of the carriers who visited the two clinics in the non-endemic area had been born outside of Kyushu, a highly endemic area, indicating that carriers will disperse from known endemic areas. Configuring an appropriate and efficient system to support carriers is necessary, especially in non-endemic areas. PMID- 26256878 TI - [The efficacy of early use of recombinant soluble thrombomodulin for disseminated intravascular coagulation complicated with hematologic malignancies]. AB - We retrospectively investigated treatment outcomes with soluble recombinant thrombomodulin (rTM) for disseminated intravascular coagulation (DIC) associated with hematological malignancies (acute leukemia and malignant lymphoma) at our hospital. After rTM administration, DIC scores improved in 29 of 39 cases with hematological malignancies (74.36%). Although one case with recurrent and refractory APL died due to cerebral bleeding during rTM administration, no bleeding-associated adverse events were observed in the other 38 cases. DIC improvement was augmented in cases with acute leukemia when rTM was introduced in the pre-DIC state. CRP decreased in 26 of 36 cases with hematological malignancies (72.22%) after rTM introduction, and CRP decreased particularly significantly in cases with malignant lymphoma, suggesting rTM to exert anti inflammatory activity. Taken together, these observations indicate that rTM, which rarely causes bleeding-associated adverse events, is an excellent agent in terms of both efficacy and safety for treating DIC associated with hematological malignancies, and the potential anti-inflammatory activity of this agent was also suggested. PMID- 26256879 TI - [Development of Ph negative acute myeloid leukemia in a patient with minor BCR/ABL positive chronic myeloid leukemia achieving a partial cytogenetic response during tyrosine kinase inhibitor treatment]. AB - A 78-year-old male, who had CKD and chronic heart failure, was referred to our hospital for evaluation of leukocytosis. His bone marrow contained 12% blast cells and chromosome analysis showed the Ph chromosome as well as other changes. The patient was diagnosed with the accelerated-phase CML because FISH and RT-PCR disclosed BCR/ABL fusion signals and minor BCR/ABL, respectively. Imatinib was administered, but the CML was resistant to this treatment. We gave him nilotinib employing a reduced and intermittent administration protocol because of the progression of anemia and heart failure. The patient achieved PCyR in 8 months, but, 12 months later, his WBC count increased and 83% of the cells were blasts. Because the probable diagnosis was the blast crisis of CML, we switched from nilotinib to dasatinib. However, leukocytosis worsened and he died of pneumonia. It was later revealed that he had a normal karyotype and both FISH and RT-PCR analysis of BCR/ABL were negative. His final diagnosis was Ph negative AML developing from Ph positive CML in PCyR. Since there were no dysplastic changes indicative of MDS, it was assumed that the AML was not secondary leukemia caused by the tyrosine kinase inhibitor but, rather, de novo AML. PMID- 26256880 TI - [Bacteremia due to Rothia mucilaginosa after chemotherapy for myeloid malignancies]. AB - The number of reported cases of bacteremia due to Rothia mucilaginosa (R. mucilaginosa), a component of the normal flora of human gastrointestinal tract mucosa, is limited. We encountered three cases of bacteremia due to R. mucilaginosa during neutropenia after chemotherapy for myeloid malignancies. Although all three patients were successfully treated with antimicrobial agents, one patient developed disseminated lesions in the lungs and soft tissue. The portal of R. mucilaginosa bacteremia is reportedly mucositis or dental disorders; however, no such complications were identified in our patients. Even in the absence of a preexisting portal, R. mucilaginosa should be recognized as a potential causative pathogen of bacteremia during neutropenic periods. Accumulations of cases and isolates are required to further elucidate the risk factors for developing R. mucilaginosa bacteremia, its clinical course, and the optimal antimicrobial treatment. PMID- 26256881 TI - [Isolated central nervous system relapse in type II enteropathy-associated T cell lymphoma]. AB - A 75-year-old male presented with progressive lower abdominal discomfort. CT scan demonstrated hypertrophy of the intestinal wall, small bowel dilatation, and masses in the descending colon. Biopsy specimens of the jejunum and descending colon revealed widespread distribution of medium-sized atypical lymphocytes with an immunophenotype, positivity for CD3, CD8, CD56, TAI-1, granzyme B and TCRbeta, but negativity for CD4, CD5, CD20, CD30 and EBER-ISH. Type II enteropathy associated T cell lymphoma (EATL; Lugano, stage IIE) was diagnosed. Subsequently, he received 6 cycles of chemotherapy with 2/3 dose CHOP and obtained complete remission. However, 18 months after the initial presentation, he presented with rapidly progressive mental deterioration. Gadolinium enhanced T1-weighted brain MR images showed multiple masses with mild heterogeneous enhancement. Brain biopsy revealed necrotic tumors composed of medium-sized atypical lymphocytes, positive for CD3, CD8, CD56, TIA-1, granzyme B and TCRbeta, but negative for CD4, CD20, and EBER-ISH. CT scan disclosed no evidence of systemic lymphoma relapse, indicating central nervous system relapse of EATL. Despite immediate high-dose chemotherapy with methotrexate, he died of disease progression. EATL is a rare disease with a very poor outcome, for which a validated standard treatment is still lacking. Further studies are needed to identify innovative therapies for treating EATL. PMID- 26256882 TI - [Brentuximab vedotin and cord blood transplantation for primary refractory Hodgkin lymphoma following autologous hematopoietic stem cell transplantation]. AB - We report a 26-year-old man with primary refractory nodular sclerosis Hodgkin lymphoma against ABVD, ICE and autologous peripheral blood stem cell transplantation (auto-PBSCT), presenting with multiple epidural spinal cord compressions, paraplegia, and generalized lymphadenopathy. We administrated four cycles of brentuximab vedotin to achieve a complete response, and then conducted cord blood transplantation. This case raises the possibility of a new strategy for refractory Hodgkin lymphoma showing residual lesions after auto-PBSCT. PMID- 26256883 TI - [Acquired pure red cell aplasia in a patient with B cell chronic lymphocytic leukemia after fludarabine therapy]. AB - A 67-year-old woman was diagnosed with chronic lymphocytic leukemia (CLL) in October 2001. In August 2004, she received chemotherapy consisting of fludarabine and cyclophosphamide (FC therapy). After three cycles of FC therapy, the number of tumor cells was markedly decreased. However, anemia progressed. She was diagnosed with pure red cell aplasia (PRCA) by bone marrow examination and was successfully treated with cyclosporin A (CsA). In October 2008, anemia progressed with the exacerbation of CLL and she received three cycles of fludarabine therapy. Although the number of tumor cells diminished, the anemia did not improve. She was diagnosed with PRCA recurrence and was again successfully treated with CsA. PRCA is a rare complication in patients with CLL and has been attributed to T cell-mediated mechanisms. Six cases with PRCA that developed after fludarabine therapy for CLL have already been reported. Fludarabine therapy may be toxic to Treg, resulting in the loss of self-tolerance. It is important to consider the possibility of PRCA in patients with progressive anemia after fludarabine therapy for CLL. PMID- 26256884 TI - [Primary graft failure in a patient with refractory acute myeloid leukemia successfully treated with modified 'one-day'-based preparative regimen followed by cord blood transplantation]. AB - A 32-year-old woman with acute myeloid leukemia failed to achieve remission with two courses of induction chemotherapy, and she received cord blood transplantation (CBT) in a non-remission state, using an HLA-matched cord blood (CB) graft after a conditioning regimen of fludarabine (Flu) at 125 mg/m2 + melphalan at 140 mg/m2 + total body irradiation (TBI) at 4 Gy. Chimerism analysis of the bone marrow (BM) cells performed on day 21 after CBT revealed 99% of these cells to be the recipient type. We diagnosed the patient as having graft failure (GF), and then carried out a second CBT using an HLA-matched male CB graft on day 29 after the first CBT. The conditioning regimen (modified 'one-day'-based regimen) consisted of Flu at 30 mg/m2 (3 days) + cyclophosphamide (CY) at 2 g/m2 (1 day) + TBI 2 Gy. She achieved neutrophil engraftment on day 18. FISH analysis of BM cells on day 13 showed 96% to be of male origin. She has remained in complete remission for 18 months, to date, since the salvage CBT. This case suggests that salvage CBT following a modified 'one-day'-based regimen may preserve a strong graft versus leukemia effect. PMID- 26256887 TI - Expression of heat shock protein 27 correlates with actin cytoskeletal dynamics and contractility of cultured human bladder smooth muscle cells. AB - Heat shock protein 27 (HSP27) is one of the most important chaperone proteins that modulates smooth muscle contraction. Here we investigated the effects of HSP27 expression on cytoskeleton dynamics and contractile function of human bladder smooth muscle cells (BSMCs) in vitro. Cultured human BSMCs were transfected with lentiviral vectors expressing either HSP27 or HSP27-siRNAs. Normal BSMCs cells and cells transfected with the empty lentivirus were used as control. Cells were then cultured on Flexcell flexible membrane dishes and mechanical stretch (14.8% elongation) was applied. The stretch caused significant disruption of actin cytoskeletal structure and decrease in F/G-actin ratio in BSMCs with HSP27 over-expression, knock-down and control groups (P<0.05) as indicated by phalloidin-FITC staining. It was also shown that the structure of actin filaments in HSP27 over-expressed cells recovered and F/G-actin ratio significantly increased at 12h after stretching compared to unstretched cells (P<0.05), but not in HSP27 knock-down cells, suggesting that HSP27 promoted the recovery of cytoskeletal structure in BSMCs from stretch-induced injury. In addition, the contractile force of BSMCs was enhanced by over-expression of HSP27 and attenuated by knock-down of HSP27 (P<0.05), suggesting a pivotal role of HSP27 in regulating bladder smooth muscle contraction. PMID- 26256888 TI - Efficient episomal reprogramming of blood mononuclear cells and differentiation to hepatocytes with functional drug metabolism. AB - The possibility of converting cells from blood mononuclear cells (MNC) to liver cells provides promising opportunities for the study of diseases and the assessment of new drugs. However, clinical applications have to meet GMP requirements and the methods for generating induced pluripotent cells (iPCs) have to avoid insertional mutagenesis, a possibility when using viral vehicles for the delivery of reprogramming factors. We have developed an efficient non-integration method for reprogramming fresh or frozen blood MNC, maintained in an optimised cytokine cocktail, to generate induced pluripotent cells. Using electroporation for the effective delivery of episomal transcription factors (Oct4, Sox2, Klf4, L Myc, and Lin28) in a feeder-free system, without any requirement for small molecules, we achieved a reprogramming efficiency of up to 0.033% (65 colonies from 2*10(5) seeded MNC). Applying the same cytokine cocktail and reprogramming methods to cord blood or fetal liver-derived CD34(+) cells, we obtained 148 iPS colonies from 10(5) seeding cells (0.148%). The iPS cell lines we generated maintained typical characteristics of pluripotent cells and could be successfully differentiated into hepatocytes with drug metabolic function. PMID- 26256889 TI - Bacterioplankton community shifts associated with epipelagic and mesopelagic waters in the Southern Ocean. AB - The Southern Ocean is among the least explored marine environments on Earth, and still little is known about regional and vertical variability in the diversity of Antarctic marine prokaryotes. In this study, the bacterioplankton community in both epipelagic and mesopelagic waters was assessed at two adjacent stations by high-throughput sequencing and quantitative PCR. Water temperature was significantly higher in the superficial photic zone, while higher salinity and dissolved oxygen were recorded in the deeper water layers. The highest abundance of the bacterioplankton was found at a depth of 75 m, corresponding to the deep chlorophyll maximum layer. Both Alphaproteobacteria and Gammaproteobacteria were the most abundant taxa throughout the water column, while more sequences affiliated to Cyanobacteria and unclassified bacteria were identified from surface and the deepest waters, respectively. Temperature was the most significant environmental variable affecting the bacterial community structure. The bacterial community composition displayed significant differences at the epipelagic layers between two stations, whereas those in the mesopelagic waters were more similar to each other. Our results indicated that the epipelagic bacterioplankton might be dominated by short-term environmental variable conditions, whereas the mesopelagic communities appeared to be structured by longer water-mass residence time and relative stable environmental factors. PMID- 26256890 TI - Liver-specific case fatality due to chronic hepatitis C virus infection: a systematic review. AB - Despite reports that mortality is increasing, overall case fatality due to hepatitis C virus (HCV) is thought to be low. Given the variability in published rates, we aimed to synthesize estimates of liver-specific case fatality and all cause mortality in chronic HCV according to follow-up duration, sustained viral response (SVR) to treatment, and liver disease severity. A systematic review was conducted of studies published in English from 2003 to 2013, reporting liver specific case fatality estimates from HCV-infected samples. Thirty-five eligible articles were identified; 26 also presented estimates of all-cause mortality. Among community-based samples, liver-specific case fatality ranged from 0.3% over 5.7 years to 9.2% over 8.2 years of follow-up; and of all-cause mortality, from 4.0% over 5.7 years, to 23.0% over 8.2 years of follow-up. Estimates were higher among clinic-based samples and those with more severe liver disease. Among treated patients achieving SVR, liver-specific case fatality was low: up to 1.4% over 11.5 years of follow-up among samples with any severity of liver disease. Estimates were higher among those without SVR: up to 14.0% over 10 years of followup among samples with any severity of liver disease, and higher still among samples with more severe liver disease. The proportion of deaths attributable to liver-specific causes ranged from 55 to 85% among those with severe liver disease. Published estimates of fatality are high among certain populations of chronic HCV patients, with liver-specific causes being an important contributor. Understanding current HCV mortality rates is important for quantifying the total burden of HCV disease. PMID- 26256891 TI - Granulocyte-colony stimulating factor for acute-on-chronic liver failure: systematic review and meta-analysis. AB - Acute-on-chronic liver failure (ACLF) is associated with increased short and long term mortality. Animal models of liver failure have demonstrated that granulocyte colony stimulating factor (G-CSF) accelerates the liver regeneration process and improves survival. However, clinical evidence regarding the use of G-CSF in ACLF remains scarce. The aim of this study was to assess the benefits and harms of G CSF in patients with acute-on-chronic liver failure. An electronic search was made in The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and LILACS up to November 2013. Randomized clinical trials comparing the use of any regimen of G-CSF against placebo or no intervention in patients with ACLF were included. Primary outcomes included overal mortality, mortality due multi-organ failure, and adverse events. Relative risk (RR) and mean difference (MD) were used. Two trials involving 102 patients were included. A significant reduction in short-term overall mortality was observed in patients receiving G CSF compared to controls (RR 0.56; 95%CI 0.39,0.80). G-CSF failed to reduce mortality secondary to gastrointestinal bleeding (RR 1.45; 95%CI 0.50, 4.27). Adverse effects reported included: fever, rash, herpes zoster, headache and nausea. In conclusion, the use of G-CSF for the treatment of patients with ACLF significantly reduced short-term mortality. While the evidence is still limited, the apparent benefit observed on short-term mortality, mild adverse effects and lack of an alternative therapy make the use of G-CSF in ACLF patients a reasonable alternative when liver transplantation is contraindicated or unavailable. PMID- 26256892 TI - Increase of drug use and genotype 3 in HCV-infected patients from Central West and Northeast Mexico. AB - BACKGROUND: The evolving pattern of HCV genotypes (GTs) and risk factors (RFs) in HCV-infected patients in Mexico is poorly understood. This study aimed to access the temporal trend of HCV GTs and RFs in HCV patients from two care centers. MATERIAL AND METHODS: Chronic HCV patients [177 and 153 patients from the Northeast (NE) and Central West (CW) regions, respectively] were selected. Baseline features were demographics, date of birth (DOB), blood transfusion before 1992 (BTb1992), RFs, sexual promiscuity (SP), dental procedure (DP), injection drug use (IDU), viral load (VL), GTs, cirrhosis status and antiviral therapy (AT). Data were analyzed by Chi-square test for trends, unpaired T-test, and logistic regression. RESULTS: HCV GT distribution was: GT1, 67%; GT2, 16%; GT3, 12% and GT4, 1%. RFs were BTb1992, 56%; surgeries, 56%; tattooing, 18% and IDU, 16%. GT1a mostly prevailed in CW than NE patients. GT1b, surgeries, BTb1992 and cirrhosis were more prevalent in older patients (p < 0.05); GT3, male gender IDU, SP, and tattooing showed an upward trend as younger were the patients in both regions (p < 0.05), contrariwise to the prevalence of GT1b. BTb1992 and surgeries were seen in elder women; BTb1992 was an independent RF for GT1. Age >= 50 years old, GT1 and exposure to AT (p < 0.05) were associated with cirrhosis. CONCLUSION: GT1a prevalence in CW Mexico remained stable, whereas GT3 increased and GT1b decreased in younger patients in both regions, along with associated RFs. Further regional molecular epidemiology and RF analyses are required in order to avoid the dissemination of new cases of HCV infection. PMID- 26256893 TI - Intermediate fibrosis staging in hepatitis C: a problem not overcome by optimal samples or pathologists' expertise. AB - BACKGROUND AND AIMS: The prediction of intermediate stage of fibrosis in chronic hepatitis C represents a prognostic factor for disease progression. Studies evaluating biopsy performance in intermediate stage considering current patterns of liver samples and pathologists' variability are scarce. We aimed to evaluate the effect of optimal liver specimens (>= 20 mm and/or >= 11 portal tracts) and pathologists' expertise on agreement for intermediate stage of fibrosis in chronic hepatitis C. MATERIAL AND METHODS: Guided biopsies with large TruCut needle were initially scored by four pathologists with different expertise in liver disease and posteriorly reviewed by a reference hepatopathologist to evaluate fibrosis agreement. RESULTS: Of the 255 biopsies initially selected, 240 met the criteria of an optimal fragment (mean length 24 +/- 5 mm; 16 +/- 6 portal tracts) and were considered for analysis. The overall agreement among all fibrosis stages was 77% (kappa = 0.66); intraobserver and interobserver agreement was, respectively, 97% (k = 0.96) and 73% (kappa = 0.60). Excluded samples (< 20 mm and < 11 portal tracts) presented a lower agreement (40%; kappa = 0.24). Stratifying fibrosis stages, an interobserver agreement of 42% was found in intermediate stage (F2), ranging from 0 to 56% according to pathologists' expertise, compared to 97% in mild (F0-F1) and 72% in advanced fibrosis (>= F3) (p < 0.001). Of the 23% misclassified cases, fibrosis understaging occurred in 82% of specimens, predominantly in F2, even when evaluated by a hepatopathologist. CONCLUSIONS: Liver biopsy presents intrinsic limitations to assess intermediate stage of fibrosis not overcome by optimal samples and experienced pathologists' analysis, and should not be considered the gold standard method to evaluate intermediate fibrosis in chronic hepatitis C. PMID- 26256894 TI - Fatty liver and abdominal fat relationships with high C-reactive protein in adults without coronary heart disease. AB - BACKGROUND AND RATIONALE: Fatty liver (FL) and abdominal visceral fat (AVF) are strongly associated with systemic inflammation, however, it has not been defined if each one is independently involved, and if the insulin resistance is associated. To investigate if FL, AVF and insulin resistance are independently or additively associated with the high-sensitivity C-reactive protein (hs-CRP) in subjects without coronary artery disease we included 491 men and 553 women. MATERIAL AND METHODS: All had anthropometric and plasma biochemical measurements, FL and AVF assessments by computed tomography. RESULTS: The FL prevalence was 35.6% in men and 28.0% in women, p < 0.01. The prevalence of obesity, metabolic syndrome and homeostasis model assessment of insulin resistance (HOMA-IR) was significantly higher in FL compared to non FL subjects. FL and AVF accounted for 21 and 17%, respectively, to hs-CRP plasma levels. FL, AVF >= P75 and HOMA-IR >= P75 were independently and additively associated with plasma hs-CRP. The risk of hs-CRP >= 3 mg/L increased progressively in men from 1.36 (0.5-3.86) through 3.58 (1.32-9.7) in those with 1 or 3 factors respectively. In women from 2.25 (1.2 4.2) to 4.67 (2.3-9.4), respectively. In conclusion, both the FL and hs-CRP >= 3 mg/L occur in 1 of every 3 non CAD subjects. In men, FL and AVF >= P75 were associated with 3.6 times the risk of hs-CRP >= 3 mg/L, while in women, these factors were independently and additively associated with a 4.7 times higher risk of systemic inflammation. PMID- 26256895 TI - SFRP5 hepatic expression is associated with non-alcoholic liver disease in morbidly obese women. AB - BACKGROUND AND AIMS: Secreted frizzled-related protein 5 (SFRP5) was recently described as a new adipokine protective for hepatic steatosis and other obesity related complications in the mouse model. To date, SFRP5 expression in non alcoholic fatty liver disease (NAFLD) has not been fully assessed in humans. We measured circulating SFRP5 levels and its expression in liver and adipose tissue, and evaluated its association with NAFLD in morbidly obese women. MATERIAL AND METHODS: Fifty-four morbidly obese women undergoing bariatric surgery were included in the study. Liver biopsies were used for histology and hepatic triglyceride content quantification. Circulating SFRP5 levels were measured through enzyme-linked immunoabsorbent assay, and SFRP5 expression was performed in hepatic and adipose tissue (subcutaneous and visceral). RESULTS: Although circulating SFRP5 levels showed a tendency to decrease with NAFLD progression, no significant differences were observed among non-alcoholic steatosis, steatohepatitis, and control subjects. Hepatic SFRP5 expression showed a negative correlation with hepatic triglyceride content (r = -0.349, P = 0.016 for mRNA and r = -0.291, P = 0.040 for SRFP5 protein) and ALT serum levels (r = -0.437, P = 0.001 for SRFP5 protein). In addition, hepatic SFRP5 protein levels were significantly lower in NASH than in control subjects (P = 0.006). CONCLUSION: This is the first study reporting an association of hepatic SFRP5 expression with NAFLD in humans. PMID- 26256896 TI - Transient hyperglycemia during liver transplantation does not affect the early graft function. AB - Background and rationale for the study. Hyperglycemia after graft reperfusion is a consistent finding in liver transplantation (LT) that remains poorly studied. We aim to describe its appearance in LT recipients of different types of grafts and its relation to the graft function. MATERIAL & METHODS: 436 LT recipients of donors after brain death (DBD), donors after cardiac death (DCD), and familial amyloidotic polyneuropathy (FAP) donors were reviewed. Serum glucose was measured at baseline, during the anhepatic phase, after graft reperfusion, and at the end of surgery. Early graft dysfunction (EAD) was assessed by Olthoff criteria. Caspase-3, IFN-gamma, IL1beta, and IL6 gene expression were measured in liver biopsy. RESULTS: The highest increase in glucose levels after reperfusion was observed in FAP LT recipients and the lowest in DCD LT recipients. Glucose level during the anhepatic phase was the only modifiable predictive variable of hyperglycemia after reperfusion. No relation was found between hyperglycemia after reperfusion and EAD. However, recipients with the highest glucose levels after reperfusion tended to achieve the best glucose control at the end of surgery and those who were unable to control the glucose value after reperfusion showed EAD more frequently. The highest levels of caspase-3 were found in recipients with the lowest glucose values after reperfusion. In conclusion, glucose levels increased after graft reperfusion to a different extent according to the donor type. Contrary to general belief, transient hyperglycemia after reperfusion does not appear to impact negatively on the liver graft function and could even be suggested as a marker of graft quality. PMID- 26256897 TI - Risk factors for acute kidney injury and 30-day mortality after liver transplantation. AB - INTRODUCTION: The aim of this study is to evaluate the risk factors for acute kidney injury (AKI) and 30-day mortality after liver transplantation. MATERIAL AND METHODS: This is a retrospective cohort of consecutive adults undergoing orthotopic liver transplantation (OLT) at a referral hospital in Brazil, from January 2013 to January 2014. Risk factors for AKI and death were investigated. RESULTS: A total 134 patients were included, with median age of 56 years. AKI was found in 46.7% of patients in the first 72 h after OLT. Risk factors for AKI were: viral hepatitis (OR 2.9, 95% CI = 1.2-7), warm ischemia time (OR 1.1, 95% CI = 1.01-1.2) and serum lactate (OR 1.3, 95%CI = 1.02-1.89). The length of intensive care unit (ICU) stay was longer in AKI group: 4 (3-7) days vs. 3 (2-4) days (p = 0.001), as well as overall hospitalization stay: 16 (9-26) days vs. 10 (8- 14) days (p = 0.001). The 30-day mortality was 15%. AKI was an independent risk factor for mortality (OR 4.3, 95% CI = 1.3-14.6). MELD-Na >= 22 was a predictor for hemodialysis need (OR 8.4, 95%CI = 1.5-46.5). Chronic kidney disease (CKD) was found in 36 patients (56.2% of AKI patients). CONCLUSIONS: Viral hepatitis, longer warm ischemia time and high levels of serum lactate are risk factors for AKI after OLT. AKI is a risk factor for death and can lead to CKD in a high percentage of patients after OLT. A high MELD-Na score is a predictor for hemodialysis need. PMID- 26256898 TI - Secondary sclerosing cholangitis following major burn. AB - BACKGROUND AND AIMS: Secondary sclerosing cholangitis in critically ill patients (SSC-CIP) is a relatively new previously unrecognized entity which may lead to severe biliary disease with rapid progression to cirrhosis. We present for the first time a case series of patients with rapidly progressive SSC-CIP requiring aggressive intensive care treatment following major burn injury. RESULTS: SSC-CIP was diagnosed in 4 consecutive patients hospitalized due to major burn injuries at our Intensive Care Unit (ICU). SSC-CIP was diagnosed when ERCP (n = 1) or MRCP (n = 3) demonstrated irregular intrahepatic bile ducts with multiple strictures and dilatations and, when a liver biopsy (n = 3) demonstrated severe cholestasis and bile duct damage. All patients were males; none of whom had pre-existing liver disease. Ages: 18-56 y. All patients suffered from severe (grade 2-3) burn injuries with total burn surface area ranging from 35 to 95%. Mean length of ICU hospitalization was 129.2 +/- 53.0 days. All patients required mechanical ventilation (with a mean PEEP of 8.4 +/- 2.1 cm H2O) and the administration of catecholamines for hemodynamic stabilization. All patients demonstrated severe cholestasis. Blood cultures and cultures from drained liver abscesses grew hospital acquired multiple resistant bacteria. Liver cirrhosis developed within 12 months. One patient underwent orthotopic liver transplantation. Two patients (50%) died. In conclusion, SSC-CIP following major burn injury is a rapidly progressive disease with a poor outcome. Liver cirrhosis developed rapidly. Awareness of this grave complication is needed for prompt diagnosis and considerations of a liver transplantation. PMID- 26256899 TI - Gallstone disease and obesity: a population-based study on abdominal fat distribution and gender differences. AB - BACKGROUND: Existing evidence suggests the visceral fat is more metabolically active than subcutaneous fat. We aimed to investigate the value of subcutaneous (SAT) and visceral adipose tissue thickness (VAT) for prediction of gallstone disease (GSD) in general population by focus on gender differences and comparison with body mass index (BMI), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR). MATERIAL AND METHODS: In this cross-sectional survey, 1,494 subjects (51.4 % men), aged above 50, randomly selected from Golestan Cohort Study residing in Gonbad City, Iran, underwent anthropometric measurements and abdominal ultrasonography. RESULTS: Prevalence of GSD was 17.8% (95% CI 15.9 19.8). Following adjustment for age and then other potential risk factors, all obesity indices, except for SAT, were associated with GSD in women with the highest odds ratio observed in WHtR (OR 1.52, 95% CI 1.22-1.89). In contrast, WHR was the only associated index in men (OR 1.49, 95% CI 1.08-2.06). The trend of increasing obesity measures across the quartiles with the risk of GSD was significant in subgroups of WHtR and BMI in women and WHR in men. No significant association was found between SAT and GSD in men or women. CONCLUSIONS: The best anthropometric indicators of the risk of GSD may differ by gender. In men, WHR might be the only preferred index to estimate risk of GSD. WHtR, WHR, VAT and BMI are associated with GSD risk in women, although WHtR might better explain this risk. SAT is the poor indicator for identifying subjects with GSD in both genders. PMID- 26256900 TI - Effect of cholecystectomy on bile acid synthesis and circulating levels of fibroblast growth factor 19. AB - Background and rationale for the study. FGF19/15 is a gut-derived hormone presumably governing bile acid (BA) synthesis and gallbladder (GB) refilling. FGF19 mRNA is present in human GB cholangiocytes (hGBECs); however, the physiological significance of GB-derived FGF19 remains unknown. We investigated whether hGBECs secrete FGF19 and the effects of cholecystectomy on serum FGF19 ([FGF19]s) and BA synthesis. MATERIAL AND METHODS: FGF19 expression was assessed by qRT-PCRs and immunostaining in hGBECs and terminal ileum, and quantified in bile and serum by ELISA. Basal and BA (chenodexycholic acid, CDCA) induced FGF19 expression and secretion was analyzed in primary cultured hGBECs and GB-d1 cell line. Pre and postprandial serum changes in [FGF19]s, 7alpha-hydroxy-4-cholestene 3-one (C4, a marker of BA synthesis) and BA were evaluated in plasma of gallstone disease patients at baseline and after cholecystectomy. RESULTS: FGF19 mRNA levels were ~250-fold higher in hGBECs compared to distal ileum. GB bile contained ~23-fold higher FGF19 levels compared to serum (p < 0.0001). CDCA induced dose-dependent expression and secretion of FGF19 in hGBECs and GB-d1 cells. Cholecystectomy increased plasma BA synthesis >= 2-fold (p < 0.0001), and altered the diurnal rhythm and significantly reduced [FGF19]s noon peak. BA serum levels, serum cholesterol and triglyceride content remained unchanged. CONCLUSIONS: In conclusion human GB cholangiocytes constitutively express and secrete high levels of FGF19 in a process regulated by BA. Resection of this organ doubles BA synthesis concomitantly with changes in [FGF19]s. These findings suggest a potential connection between GB cholangiocytes-derived FGF19 and BA metabolism that could lead to metabolic dysregulation following cholecystectomy. PMID- 26256901 TI - Etiology, outcome and prognostic factors of childhood acute liver failure in a German Single Center. AB - Pediatric acute liver failure (PALF) is a progressive, potentially fatal clinical syndrome occurring in previously healthy children. Our study aimed to determine the current leading causes of PALF in a single center in Germany, identifying possible prognostic markers. Thirty-seven pediatric patients with PALF were included. Medical records were reviewed for demographic, laboratory and clinical data. Laboratory results on admission and at peak value, PELD and MELD score on admission, and intensive care support were assessed. Fifteen patients recovered spontaneously, 14 died without transplantation, and 8 received a liver transplant. Patients who survived were significantly older than patients who died. Specific causes of PALF could be identified as infectious diseases (16%), metabolic diseases (14%), toxic liver injury (11%), immunologic diseases (8%), or vascular diseases (8%). Causes of PALF remained indeterminate in 43%. High ammonia, low albumin, and low ALT levels on admission were associated with worse outcome. Absence of need of ventilation, hemodialysis, and circulatory support predicted spontaneous recovery. In conclusion, infections are the most common known cause of PALF. However, in a large proportion of patients the cause for PALF remains cryptic. Ammonia and albumin levels may be of prognostic value to predict outcomes. PMID- 26256902 TI - Association of a novel TAS2R38 haplotype with alcohol intake among Mexican Mestizo population. AB - BACKGROUND: Alcohol intake has been associated with the bitter taste receptor T2R38. TAS2R38 gene expresses two common haplotypes: PAV and AVI. It has been reported that AVI homozygotes consume more alcohol than heterozygotes and PAV homozygotes. The aim of this study was to determine the prevalence of the TAS2R38 haplotypes among Mexican-Mestizo population and to analyze its association with alcohol intake. MATERIAL AND METHODS: In a cross-sectional study, a total of 375 unrelated Mestizo individuals were genotyped for TAS2R38 polymorphisms (A49P, V262A and I296V) by a Real-Time PCR System (TaqMan). Haplotype frequencies were calculated. Association of TAS2R38 haplotypes with alcohol intake was estimated in drinkers (DRS) and nondrinkers (NDRS). RESULTS: Two haplotypes accounted for over 96% of all haplotypes(AVV, 60%, and PAI, 36.5%). The frequency of AVV homozygotes was significantly higher in DRS than NDRS(47.2 vs. 32.2%, respectively; p < 0.05). Additionally, the AVV/AVV genotype was associated with alcohol intake when compared with heterozygotes and PAI homozygotes (OR = 1.79, 95% CI 1.13-2.84, p < 0.05 and OR = 2.23, 95% CI 1.11-4.48; p < 0.05, respectively). CONCLUSIONS: In conclusion, two TAS2R38 haplotypes(AVV and PAI) prevailed in Mexican-Mestizo population. The novel AVV haplotype was associated with alcohol intake. The high prevalence of this allelic profile in our population could help to explain, at least in part, the preference for alcohol among the Mexicans. PMID- 26256903 TI - Development of steatohepatitis in Ob/Ob mice is dependent on Toll-like receptor 4. AB - BACKGROUND AND AIM: The etiology of non-alcoholic fatty liver disease (NAFLD) progression, and why some patients develop non-alcoholic steatohepatitis (NASH) vs. uncomplicated NAFLD, is not well understood. Obesity and NAFLD are thought to be associated with high circulating levels of leptin; however, the role of leptin in NASH has been controversial. Secondly, as ob/ob mice are known to have elevated circulating levels of TLR4-stimulating endotoxin secondary to increased intestinal permeability. MATERIAL AND METHODS: We evaluated the long-term effects of steatosis on the livers of aleptinemic (OB) mice and the role of TLR4 in the development of hepatic sequelae in these animals. RESULTS: At 20 weeks of age OB animals displayed grossly steatotic livers, but also features of early stage NASH including hepatocellular ballooning and numerous necroinflammatory foci with associated changes in serum aspartate aminotransferase (AST) and alanine transaminase (ALT). TLR4 KO did not affect the development of obesity or steatosis in ob/ob mice, but protected these animals from hepatitis and liver injury. CONCLUSIONS: In conclusion, the data presented here indicate that steatohepatitis develops in the absence of leptin, and that TLR4 is integral to the development NASH secondary to hyperphagia. PMID- 26256904 TI - Swallowed chicken bone migration into the liver. PMID- 26256906 TI - Gastrointestinal neuroendocrine tumor with unresectable liver metastases: an example of multimodal therapeutic approach. AB - Gastrointestinal neuroendocrine tumors (NET) frequently present with unresectable hepatic metastases, which poses a barrier for curative treatment. Resection of the primary tumor and subsequent orthotopic liver transplantation (OLT) has been proposed as a treatment approach but available data in this regard is limited. We present a clinical case of an otherwise asymptomatic 44-yo man complaining of abdominal pain and dyspepsia that was diagnosed of a 10 cm duodenal tumor with multiple hepatic metastases. A CT-guided biopsy confirmed a NET. He underwent first a Whipple's procedure, and then was listed for liver transplantation. During the waiting time a multimodal therapeutic approach was used including the use of radioactive 177lutetium-labeled somatostatin analogues, long-acting somastostatin analogues and antiangiogenic antibodies (bevacizumab) in order to keep neoplastic disease under control. Two years after Whipple's procedure and given disease stability he underwent OLT with an uneventful postoperative evolution. Patient condition and graft function are optimal after a 4-year follow up period with no evidence of recurrence. This case report underscores how a multimodal approach involving careful patient selection, resective surgery as well as use of somatostatin analogues and antiangiogenic biological therapy followed by liver transplantation can achieve excellent long-term results in this difficult patient population. PMID- 26256905 TI - Reversal of advanced fibrosis after long-term ursodeoxycholic acid therapy in a patient with residual expression of MDR3. AB - INTRODUCTION: Progressive familial intrahepatic cholestasis type 3 (PFIC-3) is a severe liver disorder associated with inherited dysfunction of multidrug resistance protein 3 (MDR3/ABCB4), which functions as a phospholipid floppase, translocating phosphatidylcholine from the inner to the outer hemileaflet of the canalicular membrane of hepatocytes. MDR3 deficiency results in a disbalanced bile which may damage the luminal membrane of cells of the hepatobiliary system. We evaluated clinical, biochemical and histological improvement in a genetically proven PFIC-3 patient after long-term ursodeoxycholic acid (UDCA) administration. MATERIAL AND METHODS: A PFIC-3 patient and a relative with cholestatic liver disease were studied. Hepatic MDR3 expression was analyzed by immunohistochemistry and ABCB4 mutations were identified. The effect of the mutations on MDR3 expression and subcellular localization was studied in vitro. RESULTS: A 23-year-old man presented cholestasis with severe fibrosis and incomplete cirrhosis. Canalicular staining for MDR3 was faint. Sequence analysis of ABCB4 revealed two missense mutations that reduce drastically protein expression levels. After 9 years of treatment with UDCA disappearance of fibrosis and cirrhosis was achieved. CONCLUSION: These data indicate that fibrosis associated with MDR3 deficiency can be reversed by long-term treatment with UDCA, at least when there is residual expression of the protein. PMID- 26256907 TI - Cholestatic hepatitis C after chemotherapy containing rituximab in diffuse large B cell lymphoma. AB - Rituximab is a chimeric anti-CD20 monoclonal antibody that is a widely used for the treatment of B cells non-Hodgkin lymphoma. The use of chemotherapy regimens containing rituximab in HCV-positive patients with non-Hodgkin lymphoma has been associated with liver dysfunction, but no cases of cholestatic hepatitis C were described. To our knowledge, this is the first case of cholestatic hepatitis C in an HCV-positive patient with diffuse large B-cell lymphoma describes in the literature. We discuss the pathogenetic mechanisms underlying this severe form of hepatitis and describe its evolution after antiviral treatment. PMID- 26256908 TI - Fecal transplant to mitigate hyperammonemia and hepatic encephalopathy in animal models. PMID- 26256910 TI - Prognostic significance of changes in red cell distribution width in an internal medicine ward. AB - BACKGROUND: The prognostic significance of red cell distribution width (RDW) during hospitalization in internal medicine wards was not sufficiently investigated. METHODS: Demographic, clinical and laboratory characteristics were collected from 586 internal medicine inpatients. Following discharge, all-cause mortality was recorded. The data were compared according to DeltaRDW during hospitalization (primary endpoint), and to normal (<=14.7%) vs. high (>14.7%) RDW values on admission/discharge (secondary endpoint). RESULTS: Group A (rise in RDW, DeltaRDW +0.4%), group B (nonsignificant RDW changes, DeltaRDW up to 0.4%) and group C (drop in RDW, DeltaRDW -0.4%) comprised 20.3%, 60.6% and 19.1% of the patients, respectively. High RDW on admission and discharge was found in 31.7% and 31.4% of patients, respectively. In-hospital mortality rates were higher in group A than in groups B and C (14.3% vs. 2.8% and 4.5%, p<0.001), whereas increased long-term (median follow-up 43 months) mortality rates were observed in group C (35.7%), compared to groups A (17.6%) and B (23.4%), p=0.009. Mortality rates were significantly higher (p<0.001) in patients with high than normal RDW on admission (51.1% vs. 20.3%) and on discharge (50.5% vs. 20.6%). Every 1% increment of RDW on admission and discharge strongly predicted mortality (relative risks 1.21 and 1.21; 95% confidence intervals 1.12-1.31 and 1.13-1.32, respectively). CONCLUSIONS: High RDW on admission and discharge predicted poor prognosis. Rising RDW throughout hospitalization was associated with higher in hospital mortality, while an elevated long-term mortality rate was observed in patients with declining RDW. Repeated RDW measurements may improve risk stratification for internal medicine inpatients. PMID- 26256909 TI - The Use of Recombinant Tissue Plasminogen Activator (rTPA) in The Treatment of Fibrinous Pleuropneumonia in Horses: 25 Cases (2007-2012). AB - BACKGROUND: Information about treatment protocols, adverse effects and outcomes with intrapleural recombinant tissue plasminogen activator (rTPA) use in horses with fibrinous pleuropneumonia is limited. HYPOTHESIS/OBJECTIVES: Describe factors that contribute to clinical response and survival of horses treated with rTPA intrapleurally. ANIMALS: Horses with bacterial pneumonia and fibrinous pleural effusion diagnosed by ultrasonography, that were treated with rTPA intrapleurally. METHODS: Retrospective multicenter case series from 2007-2012. Signalment, history, clinical and laboratory evaluation, treatment, and outcome obtained from medical records. Regression analysis used to identify associations between treatments and outcomes. RESULTS: Thirty three hemithoraces were treated in 25 horses, with 55 separate treatments. Recombinant tissue plasminogen activator (375-20,000 MUg/hemithorax) was administered 1-4 times. Sonographically visible reduction in fibrin mat thickness, loculations, fluid depth, or some combination of these was seen in 32/49 (65%) treatments. Response to at least 1 treatment was seen in 17/20 (85%) horses with sonographic follow-up evaluation after every treatment. Earlier onset of rTPA treatment associated with increased survival odds. No association was found between cumulative rTPA dose or number of rTPA doses and survival, development of complications, duration of hospitalization or total charges. Clinical evidence of hypocoagulability or bleeding was not observed. Eighteen horses (72%) survived to discharge. CONCLUSIONS AND CLINICAL IMPORTANCE: Treatment with rTPA appeared safe and resulted in variable changes in fibrin quantity and organization within the pleural space. Recombinant tissue plasminogen activator could be a useful adjunct to standard treatment of fibrinous pleuropneumonia, but optimal case selection and dosing regimen remain to be elucidated. PMID- 26256911 TI - Evaluation of socio-economic inequalities in the use of maternal health services in rural western China. AB - OBJECTIVES: To describe the use of maternal health services according to the standards of the Chinese Ministry of Health, and assess socio-economic inequalities in usage in rural Shaanxi province, western China. STUDY DESIGN: Cross-sectional survey. METHODS: Principal components analysis was used to measure the economic status of households. A concentration index (CI) approach was used as a measure of socio-economic inequalities in the use of maternal health services, and a decomposable CI was used to identify the factors that contributed to the socio-economic inequalities in usage. RESULTS: In total, 4760 women who had given birth in the preceding three years were selected at random to be interviewed in the five counties. Household wealth index was calculated by constructing a linear index from asset ownership indicators using principal components analysis to derive weights. The CI approach is a standard measure in the analysis of inequalities in health. If the CI for the use of maternal health services is positive, it is pro-rich; if it is negative, it is pro-poor. The decomposition method was used to estimate the contributions of individual factors to CI. The overall CI for five or more prenatal visits was 0.075. The household wealth index was found to make the greatest contribution to socio-economic inequalities for five or more prenatal visits (35.5%), followed by maternal education (28.8%), receipt of a health handbook during pregnancy (12.1%), age group (11.0%), distance from health facility (10.5%), family members (1.5%) and district of residence (0.6%). CONCLUSIONS: Socio-economic inequalities in the use of prenatal health services were pro-rich in rural western China. Socio-economic inequalities in hospital delivery and postnatal health check-ups were not evident. Improving household economic status, providing prenatal health services for women with low income and low educational level, providing health handbooks and improving traffic conditions should be promoted as methods to eliminate socio economic inequalities in the use of maternal health services. PMID- 26256912 TI - Perception of health risks among adolescents due to consumption of cigarettes, alcohol and psychoactive substances in the Federation of Bosnia and Herzegovina. AB - OBJECTIVES: This article describes the perception of health risks in adolescents due to the consumption of cigarettes, alcohol and psychoactive substances in the Federation of Bosnia and Herzegovina (FBIH), as well as their observation of the behavior of their peers related to addictive behaviors. METHODS: For the analysis was used a database from the European School Survey Project on Alcohol and Other Drugs (ESPAD) survey which was conducted in FBIH in 2011. The target population were students in the second grade of secondary schools in FBIH born in 1995 according to the ESPAD protocol. The total number of respondents from the cohort born in 1995 was 3813 students. RESULTS: The research results showed that the prevalence of risk perception due to the consumption of cigarettes, alcohol and psychoactive substances among adolescents in the FBIH is lower than the mean prevalence in countries which have implemented the ESPAD survey of 2011. CONCLUSIONS: PPreventive activities should be aimed at adolescent risk behaviours and empower them to make the right decisions that can have far reaching significance. Attention has to be paid to selective prevention that is directed towards individuals or subgroup of population where the risk of developing disorder is much higher than average. PMID- 26256913 TI - Multifunctional MWCNTs-NaGdF4:Yb(3+),Er(3+),Eu(3+) hybrid nanocomposites with potential dual-mode luminescence, magnetism and photothermal properties. AB - A novel dual-mode luminescence multifunctional hybrid nanomaterial has been successfully prepared by coating the NaGdF4:Yb(3+),Er(3+),Eu(3+) nanoparticles (NPs) on the surface of MWCNTs. The as-synthesized MWCNTs NaGdF4:Yb(3+),Er(3+),Eu(3+) nanocomposites (NCs) can simultaneously take advantage of both magnetic and optical properties of NaGdF4:Yb(3+),Er(3+),Eu(3+) NPs and the photothermal conversion property of MWCNTs. The samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectrometry (EDS), vibrating sample magnetometry (VSM), UV-Vis absorption, luminescence spectroscopy and fluorescence lifetime measurements. Meanwhile, the photothermal conversion was examined under irradiation with a 980 nm laser. The results show that the MWCNTs NaGdF4:Yb(3+),Er(3+),Eu(3+) NCs have preferably magnetic, dual-mode (up- and down conversion) luminescence and photothermal properties. And the NCs have good biocompatibility, low toxicity and up-conversion luminescence for cell imaging. As a consequence, the dual-mode luminescence multifunctional nanomaterials have potential applications in environmental science fields and clinical fields for magnetic resonance imaging, fluorescence imaging, photothermal therapy, bioseparation and targeted drug delivery. PMID- 26256914 TI - Factors related to occurrence and aggravation of pancreatic fistula after radical gastrectomy for gastric cancer. AB - BACKGROUND AND OBJECTIVES: Pancreatic fistula (PF) and subsequent intra-abdominal abscess is a serious complication after gastrectomy for gastric cancer. The study aims to evaluate amylase concentration of drainage fluid (d-AMY) and serum C reactive protein (CRP) as the predictive factors related to PF amounting to Clavien-Dindo (CD) grade III. METHODS: 448 patients who underwent gastrectomy for gastric cancer were analyzed. Closed drains were placed in the left subphrenic cavity and/or Winslow's cavity depending on the procedures. The cutoff values of d-AMY and CRP were determined, and their roles as predictive factors for CD grade III PF were evaluated. RESULTS: PF, diagnosed in 58 patients, was stratified according to the CD classification. Consequently, grade III PF which includes PF related abscesses was observed in 32 patients. The cutoff value of d-AMY on the first postoperative day for predicting grade III PF was 1949 IU/l. The cutoff value of CRP on the third postoperative day for the same purpose was 20.44 mg/dl. Multivariate analysis demonstrated that d-AMY and CRP were significant predictive factors for grade III PF. CONCLUSIONS: The d-AMY on the first postoperative day and CRP on the third postoperative day might be useful for predicting CD grade III PF after gastrectomy. PMID- 26256915 TI - A lean neck mass clinic model: Adding value to care. AB - OBJECTIVES/HYPOTHESIS: To demonstrate that ultrasound-guided fine needle aspiration (USFNA) with on-site cytopathologic analysis eliminates unnecessary diagnostic testing, return visits, and repeat procedures and optimizes quality of care. STUDY DESIGN: Retrospective cohort. METHODS: Sixty-one new patients (28 female; 33 male; age range=19-85 years) were seen in our dedicated neck mass clinic over a 1-year period. All patients underwent USFNA of masses located in neck levels I-VI (n=40), parotid gland (n=20), or parapharyngeal space (n=1). Each patient underwent two USFNA passes followed by on-site cytopathologic analysis with additional passes if required for diagnosis. RESULTS: Diagnosis was made in 93.4% (n=57) of patients, allowing for counseling and treatment planning at the first visit. To obtain a diagnosis, more than half (57.4%, n=35) of our patients required additional passes, which implies that they would have required an additional visit without on-site cytopathologic analysis. Treatment included observation in 42.6% (n=26) of patients, surgery in 32.8 % (n=20) of patients, and nonsurgical treatment (chemotherapy, radiation, other) in 24.6% (n=15) of patients. The average time from check-in to checkout including the clinic visit, biopsy, and treatment counseling was 103 minutes, and the average round trip mileage traveled per patient was 127.6 miles. CONCLUSIONS: The adult neck mass is a commonly encountered scenario in otolaryngology. For the patient, this can be a stressful situation in which timely and accurate diagnosis is critical. A dedicated lean neck mass clinic model with USFNA and on-site cytopathologic analysis can be both an efficient part of one's practice and a valuable addition to patient care. LEVEL OF EVIDENCE: 4. PMID- 26256916 TI - Personality, attrition and weight loss in treatment seeking women with obesity. AB - Studies on small samples or in single units applying specific treatment programmes found an association between some personality traits and attrition and weight loss in individuals treated for obesity. We aimed to investigate whether pre-treatment personality traits were associated with weight loss outcomes in the general population of women with obesity. Attrition and weight loss outcomes after 12 months were measured in 634 women with obesity (mean age, 48; body mass index (BMI), 37.8 kg m(-2)) seeking treatment at eight Italian medical centres, applying different medical/cognitive behavioural programmes. Personality traits were assessed with the Temperament and Character Inventory (TCI), eating disorder features with the Binge Eating Scale (BES) and Night Eating Questionnaire (NEQ). Within the 12-month observation period, 32.3% of cases were lost to follow-up. After adjustment for demographic confounders and the severity of eating disorders, no TCI personality traits were significantly associated with attrition, while low scores of the novelty seeking temperament scale remained significantly associated with weight loss >= 10% (odds ratio, 0.983; 95% confidence interval, 0.975-0.992). Additional adjustment for education and job did not change the results. We conclude that personality does not systematically influence attrition in women with obesity enrolled into weight loss programmes in the community, whereas an association is maintained between novelty seeking and weight loss outcome. Studies adapting obesity interventions on the basis of individual novelty seeking scores might be warranted to maximize the results on body weight. PMID- 26256917 TI - In-tube electro-membrane extraction with a sub-microliter organic solvent consumption as an efficient technique for synthetic food dyes determination in foodstuff samples. AB - A simple and efficient extraction technique with a sub-microliter organic solvent consumption termed as in-tube electro-membrane extraction (IEME) is introduced. This method is based upon the electro-kinetic migration of ionized compounds by the application of an electrical potential difference. For this purpose, a thin polypropylene (PP) sheet placed inside a tube acts as a support for the membrane solvent, and 30MUL of an aqueous acceptor solution is separated by this solvent from 1.2mL of an aqueous donor solution. This method yielded high extraction recoveries (63-81%), and the consumption of the organic solvent used was only 0.5MUL. By performing this method, the purification is high, and the utilization of the organic solvent, used as a mediator, is very simple and repeatable. The proposed method was evaluated by extraction of four synthetic food dyes (Amaranth, Ponceau 4R, Allura Red, and Carmoisine) as the model analytes. Optimization of variables affecting the method was carried out in order to achieve the best extraction efficiency. These variables were the type of membrane solvent, applied extraction voltage, extraction time, pH range, and concentration of salt added. Under the optimized conditions, IEME-HPLC-UV provided a good linearity in the range of 1.00-800ngmL(-1), low limits of detection (0.3-1ngmL( 1)), and good extraction repeatabilities (RSDs below 5.2%, n=5). It seems that this design is a proper one for the automation of the method. Also the consumption of the organic solvent in a sub-microliter scale, and its simplicity, high efficiency, and high purification can help one getting closer to the objectives of the green chemistry. PMID- 26256918 TI - Development and validation of a simple high performance liquid chromatography - evaporative light scattering detector method for direct quantification of native cyclodextrins in a cyclization medium. AB - A simple HPLC-ELSD method was developed for the separation and quantification of native cyclodextrins. The technique was validated in the presence of two interfering matrices composed of byproducts from the cyclization medium. A fast separation of the compounds was achieved (in <20min) using a NUCLEODUR((r)) C18 Pyramid column (150mm*4.6mm; particle size 5MUm) at 30 degrees C. The analytes were eluted using a linear gradient of acetonitrile and water containing 1% (v/v) of acetic acid at a flow rate of 0.3mL/min. Validation results showed that the method was accurate (93-110%) and selective. The precision was <=5.7% for a hydrolyzed starch blank matrix spiked with cyclodextrins, and <=6.2% for a blank matrix composed of a mixture of dextrin and glucose spiked with cyclodextrins. The limit of quantification was 0.05g/L for alpha- and 0.06g/L for beta- and gamma-cyclodextrins. The new HPLC-ELSD method could accurately quantify the three cyclodextrins directly in a cyclization medium, without pretreatment of the samples. PMID- 26256919 TI - Alleviating nonlinear behavior of disulfide isoforms in the reversed-phase liquid chromatography of IgG2. AB - Reversed-phase chromatography is an established method for characterizing the disulfide isoforms of IgG2. This work explores the effect of mobile phase gradient profile and sample concentration on the separation of disulfide isoforms. The acidic mobile phase can alter the relative proportions of disulfide isoforms, but only when the level of the reactive A1 isoform is much higher than for typical conditions of separation and typical IgG2 samples. Otherwise, there is minimal disulfide scrambling. A slower gradient and flow rate modestly improve resolution, but the peaks remain heavily overlapped. Resolution is further improved and nonlinear chromatography lessened when injection is performed under non-stacking conditions. Non-stacking conditions also keep the concentration from spiking at the head of the column, reducing noncovalent associations that can promote disulfide scrambling. The higher resolution from non-stacking injection reveals the presence of at least seven species. PMID- 26256920 TI - Ion-exchange molecularly imprinted polymer for the extraction of negatively charged acesulfame from wastewater samples. AB - Acesulfame is a known indicator that is used to identify the introduction of domestic wastewater into water systems. It is negatively charged and highly water soluble at environmental pH values. In this study, a molecularly imprinted polymer (MIP) was synthesized for negatively charged acesulfame and successfully applied for the selective solid phase extraction (SPE) of acesulfame from influent and effluent wastewater samples. (Vinylbenzyl)trimethylammonium chloride (VBTA) was used as a novel phase transfer reagent, which enhanced the solubility of negatively charged acesulfame in the organic solvent (porogen) and served as a functional monomer in MIP synthesis. Different molecularly imprinted polymers were synthesized to optimize the extraction capability of acesulfame. The different materials were evaluated using equilibrium rebinding experiments, selectivity experiments and scanning electron microscopy (SEM). The most efficient MIP was used in a molecularly imprinted-solid phase extraction (MISPE) protocol to extract acesulfame from wastewater samples. Using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) analysis, detection and quantification limits were achieved at 0.12MUgL(-1) and 0.35MUgL(-1), respectively. Certain cross selectivity for the chemical compounds containing negatively charged sulfonamide functional group was observed during selectivity experiments. PMID- 26256921 TI - Optimization of dispersive micro solid-phase extraction for the rapid determination of benzophenone-type ultraviolet absorbers in aqueous samples. AB - A solvent-free method for the rapid analysis of six benzophenone-type UV absorbers in water samples is described. The method involves the use of dispersive micro solid-phase extraction (DmSPE) followed by the simultaneous silylation and thermal desorption (SSTD) gas chromatography-mass spectrometry (GC MS) operating in the selected-ion-storage (SIS) mode. A Plackett-Burman design was used for screening and a central composite design (CCD) for optimizing the significant factors was applied. The optimal experimental conditions involved immersing 1.5mg of the Oasis HLB adsorbent in a 10mL portion of water sample. After vigorous shaking for 1min, the adsorbents were transferred to a micro-vial, and were dried at 122 degrees C for 3.5min, after cooling, 2MUL of the BSTFA silylating reagent was added. For SSTD, the injection-port temperature was held at 70 degrees C for 2.5min for derivatization, and the temperature was then rapidly increased to 340 degrees C to allow the thermal desorption of the TMS derivatives into the GC for 5.7min. The limits of quantitation (LOQs) were determined to be 1.5-5.0ng/L. Precision, as indicated by relative standard deviations (RSDs), was equal or less than 11% for both intra- and inter-day analysis. Accuracy, expressed as the mean extraction recovery, was between 87% and 95%. A preliminary analysis of the municipal wastewater treatment plant (MWTP) effluent and river water samples revealed that 2-hydroxy-4 methoxybenzophenone (BP-3) was the most common benzophenone-type UV absorber present. Using a standard addition method, the total concentrations of these compounds ranged from 5.1 to 74.8ng/L. PMID- 26256922 TI - A charged aerosol detector/chemiluminescent nitrogen detector/liquid chromatography/mass spectrometry system for regular and fragment compound analysis in drug discovery. AB - In this paper, we introduce a high throughput LCMS/UV/CAD/CLND system that improves upon previously reported systems by increasing both the quantitation accuracy and the range of compounds amenable to testing, in particular, low molecular weight "fragment" compounds. This system consists of a charged aerosol detector (CAD) and chemiluminescent nitrogen detector (CLND) added to a LCMS/UV system. Our results show that the addition of CAD and CLND to LCMS/UV is more reliable for concentration determination for a wider range of compounds than either detector alone. Our setup also allows for the parallel analysis of each sample by all four detectors and so does not significantly increase run time per sample. PMID- 26256923 TI - Antibody-free ultra-high performance liquid chromatography/tandem mass spectrometry measurement of angiotensin I and II using magnetic epitope-imprinted polymers. AB - The major challenges in measuring plasma renin activity (PRA) stem from the complexity of biological matrix, as well as from the instability and low circulating concentration of angiotensin. In this study, an ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) based technique has been developed for the measurement of angiotensin using magnetically imprinted polymers for simultaneous enrichment of the precursor peptide angiotensin II (Ang II) and the upstream peptide precursor angiotensin I (Ang I). This technique involved surface graft imprinting in aqueous solutions using vinyl-modified nano-iron oxide as solid supports, the specificity determinant of Ang I and Ang II as the epitope, and methacrylic acid and N-t butylacrylamide as functional monomers. The vinyl-modified nano-iron oxide acted as a magnetic separation media, and the molecularly imprinted shell provided analyte selectivity for the recognition of Ang I and Ang II. Selective enrichment of Ang I and Ang II was accomplished by the magnetically imprinted polymers, followed by a magnetic separation procedure and subsequent quantification by UPLC MS/MS in the positive ionization mode with multiple reaction monitoring. Through the latter protocol, a low limit of detection could be realized, viz. 0.07ng/mL and 0.06ng/mL for Ang I and II, respectively, which was thoroughly validated for accuracy and reproducibility through analyzing Ang I and Ang II in human plasma samples. PMID- 26256924 TI - Molecularly imprinted polymers as a tool for the study of the 4-ethylphenol metabolic pathway in red wines. AB - A molecularly imprinted polymer (MIP) based methodology is described here for the determination of compounds that belong to the 4-ethylphenol (4EP) metabolic pathway in red wines. To this end, two MIP materials have been developed: a 4EP MIP as a class-selective material to extract phenols that belong to the 4EP metabolic pathway and a coumaric acid (CA) imprinted polymer as a MIP-based stationary phase capable of selectively separating these phenols on HPLC analysis, obtaining clean chromatograms. 4-vinyl pyridine and ethylene glycol dimethacrylate were respectively used as functional monomer and cross-linker for both MIPs. Once polymer compositions were optimised, the 4EP MIP was packed into SPE cartridges for wine sample clean-up and CA MIP was packed into HPLC columns to chromatographically separate the compounds present in the eluates obtained after SPE extraction. The accuracy of the proposed method was tested spiking wine samples with known concentrations of target compounds and subsequently, analytes were quantified by the standard addition method. Registered mean recoveries ranged from 95.2 to 109.2% and RSD values were below 10% in most cases. The described methodology was found to be suitable for the selective extraction and quantification of the compounds that belong to the 4EP metabolic pathway in red wines with minimal matrix effects and could be undoubtedly exploited to monitor 4EP and its precursors in wines. PMID- 26256925 TI - Off-label and unlicensed use of medicinal products in the neonatal setting in the Slovak Republic. AB - BACKGROUND: Frequent prescription of medication in an unapproved manner (off label or unlicensed) in the neonatal setting is a result of the limited availability of adequately studied drugs in the pediatric population. Given that little information is available on this issue from eastern European countries, the purpose of this study was to describe for the first time the extent and pattern of off-label or unlicensed use of medicines in newborns in the Slovak Republic. METHODS: Cross-sectional study was performed at the Department of Pathological Newborns of Children's University Hospital, Bratislava, and Unit of Pathological Newborns of Teaching Hospital Nitra. Data were collected on hospitalized neonates admitted between 1 April and 30 September 2012 who received pharmacotherapy. Label status of the administered drugs was determined according to the Slovak Summaries of Product Characteristics. RESULTS: A total of 962 prescriptions referring to 97 different medications was administered to 202 hospitalized newborns (46% premature). Anti-infectives and alimentary drugs were the most commonly prescribed. Of all prescriptions, 43% were identified as off label and 4.8% as unlicensed. At least one off-label or unlicensed drug was given to 88.6% of patients. Ketoconazole was the most frequent drug used in an unapproved manner. A total of 13.8% of all prescriptions was administered despite contraindication. CONCLUSIONS: Administration of drugs to newborns in an unapproved manner was common in the participating Slovak neonatal wards, reflecting the lack of appropriate pediatric drug labeling. PMID- 26256926 TI - Improved mechanical stability of HKUST-1 in confined nanospace. AB - One of the main concerns in the technological application of several metal organic frameworks (MOFs) relates to their structural instability under pressure (after a conforming step). Here we report for the first time that mechanical instability can be highly improved via nucleation and growth of MOF nanocrystals in the confined nanospace of activated carbons. PMID- 26256927 TI - [Graft-versus-host disease associated with lenalidomide maintenance after allogeneic transplantation for relapsed/refractory multiple myeloma]. AB - Although allogeneic stem cell transplantation (allo-SCT) is a potentially curative treatment option for multiple myeloma (MM), it is not recognized as a standard of care because of the high associated incidences of both treatment related mortality and relapse. We administered lenalidomide (Len) as maintenance therapy for patients with MM undergoing allo-SCT who were at high risk of disease relapse. Graft-versus-host disease was induced by Len administration in two patients, but was manageable with dose reduction. Although Len has a direct anti myeloma effect and can also induce tumor immunity against residual myeloma cells, it is important to identify how to optimize the safety and the effects of Len administration after allo-SCT. Further accumulation of data including those from prospective clinical trials is urgently needed. PMID- 26256928 TI - [Acquired von Willebrand syndrome in a patient with immune thrombocytopenic purpura]. AB - Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder similar to inherited von Willebrand disease. We describe a 78-year-old woman with coexistent idiopathic thrombocytopenic purpura (ITP) and AVWS. The patient had once been admitted to our hospital because of cerebral infarction. Her platelet count had been normal at that time. Ten years later, she showed a severe bleeding tendency (platelet count 3.2*10(4)/MUl). Analysis of hemostatic parameters showed very low (<6%) von Willebrand factor ristocetin cofactor (vWF: Rco), and low VIII: C (22%), but elevated (276%) von Willebrand antigen. Electrophoretic analysis of plasma showed low levels of the high-molecular weight VWF multimer. The presence of antibodies (IgG1 and IgG4) to VWF was detected by enzyme linked immunosorbent assay (ELISA). Factor XIII activity was 42%. Treatment with corticosteroids did not improve the thrombocytopenia, but did correct the bleeding diathesis. Also, VWF: Rco and VIII: C showed normalization. These findings indicated that the patient had ITP associated with AVWS. All reported cases of AVWS associated with systemic lupus erythematosus were cured by appropriate treatment of the underlying autoimmune disease with prednisone or immunosuppression. This bleeding disorder occurs mainly in patients with lymphoproliferative, myeloproliferative, cardiovascular and immunologic disorders, but no patients with ITP have previously been reported. This patient had the rare presentation of AVWS complicated by ITP and factor XIII deficiency. PMID- 26256929 TI - [Successful treatment with dose-adjusted EPOCH-R for triple-hit lymphoma having BCL2, BCL6 and MYC translocations]. AB - Double- and triple-hit lymphomas (DHL/THL), high-grade B-cell lymphomas with an extremely poor prognosis, are defined by a chromosomal breakpoint affecting the MYC/8q24 locus in combination with another recurrent breakpoint. The successful use of dose-adjusted (DA) EPOCH-R in patients with MYC-positive lymphoma and Burkitt lymphoma (BL) was recently reported. A 74-year-old man with acute renal dysfunction and hyperkalemia was transferred to our emergency center by ambulance. PET-CT revealed a left renal hilar mass enveloping the abdominal para aortic domain and bladder and hydronephrosis. High (18)F-FDG uptake revealed lymph node, peritoneum, and multiple bone metastases. Analysis of the bone marrow aspirate revealed abnormal lymphoid cells with deeply basophilic cytoplasm and numerous vacuoles resembling Burkitt cells. Chromosomal analysis revealed a complex chromosomal karyotype, including t(14;18)(q32;q21), and FISH analysis confirmed split BCL2, BCL6, and MYC signals. Bone marrow biopsy revealed diffusely infiltrating large abnormal lymphoid cells with a CD10+, CD20+, BCL2+, BCL6+, c-MYC+ and MUM1(-) immunophenotype. B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and BL, was diagnosed. The patient achieved a partial response after eight courses of DA EPOCH-R chemotherapy. Our experience suggests that DA-EPOCH-R may be an effective treatment for DHL/THL. PMID- 26256930 TI - [Cutaneous extramedullary hematopoiesis associated with myelodysplastic/myeloproliferative neoplasm, unclassifiable]. AB - Cutaneous extramedullary hematopoiesis has been reported in a small number of patients with myelofibrosis. A 79-year-old male with JAK2V617F-positive myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS-MPN-U), presented with multiple skin lesions. The skin lesions were papulonodular, reddish brown, and elastic hard on palpation. Based on a lesion biopsy, cutaneous extramedullary hematopoiesis associated with MDS/MPN-U was diagnosed. He died four months later due to exacerbation of MDS/MPN-U. Cutaneous invasion might be associated with progressive disease and a poor prognosis for MDS/MPN-U, as it is for myelofibrosis. PMID- 26256931 TI - [Evaluation of the enhanced International Prognostic Index (NCCN-IPI) for cases with diffuse large B-cell lymphoma]. AB - The NCCN-International Prognostic Index (IPI) is reported to be more powerful than the former IPI for predicting survival in the rituximab era. To evaluate the NCCN-IPI in our institutions, we analyzed 188 patients with diffuse large B-cell lymphoma treated with rituximab plus CHOP or THP-COP chemotherapy. The 5-year overall survival rates of patients with low, low-intermediate, high-intermediate, and high risk were 90%, 76%, 64%, and 34%, respectively. Although there was no difference in overall survival between patients 61-75 and those >75 years of age, the NCCN-IPI is useful for classifying prognostically relevant subgroups of Japanese patients. PMID- 26256933 TI - [Erratum]. PMID- 26256935 TI - Reaction kinetics for the solid state synthesis of the AlH3/MgCl2 nano-composite by mechanical milling. AB - The process of mechanical milling has been proved to be a cost-effective way to synthesize the AlH3/MgCl2 nano-composite by using MgH2 and AlCl3 as reagents. However, so far there is no comprehensive knowledge of the kinetics of this process. In an effort to predict the reaction progress and optimize the milling parameters, the kinetics of the synthesis of the AlH3/MgCl2 nano-composite by mechanical milling of MgH2 and AlCl3 is experimentally investigated in the present work. The reaction progress or the transformation fraction upon milling for different times is evaluated using the isothermal hydrogen desorption test of the as-milled samples at 220 degrees C, which is much lower than the threshold temperature for the de-hydriding of the reagent MgH2 but enough for the de hydriding of the as-synthesized nano-sized AlH3. The effects of milling parameters on the reaction kinetics as well as the underlying mechanism are discussed by referring to the mechanical energy input intensity, the vial temperature and the Gibbs free energy change for the reaction. Furthermore, it is found that the Johnson-Mehl-Avrami (JMA) model can well describe the kinetics theoretically. By fitting the experimental data with the JMA expression, the theoretical kinetics expressions, the equation parameters, and the activation energy are obtained. PMID- 26256934 TI - Minimally invasive surgery fellowship graduates: Their demographics, practice patterns, and contributions. AB - BACKGROUND: Fellowship opportunities in minimally invasive surgery, bariatric, gastrointestinal, and hepatobiliary arose to address unmet training needs. The large cohort of non-Accreditation Council for Graduate Medical Education accredited fellowship graduates (NACGMEG) has been difficult to track. In this, the largest survey of graduates to date, our goal was to characterize this unique group's demographics and professional activities. STUDY DESIGN: A total of 580 NACGMEG were surveyed covering 150 data points: demographics, practice patterns, academics, lifestyle, leadership, and maintenance of certification. RESULTS: Of 580 previous fellows, 234 responded. Demographics included: average age 37 years, 84% male, 75% in urban settings, 49% in purely academic practice, and 58% in practice <5 years. They averaged 337 operating room cases/year (approximately 400/year for private practice vs 300/year for academic). NACGMEG averaged 100 flexible endoscopies/year (61 esophagogastroduodenoscopies, 39 colon). In the past 24 months, 60% had submitted abstracts to a national meeting, and 54% submitted manuscripts to peer-reviewed journals. Subset analyses revealed relevant relationships. There was high satisfaction (98%) that their fellowship experience met expectations; 78% termed their fellowships, versus 50% for residencies, highly pertinent to their current practices. 63% of previous fellows occupy local leadership roles, and most engage in maintenance of certification activities. CONCLUSION: Fellowship alumnae appear to be productive contributors to American surgery. They are clinically and academically active, believe endoscopy is important, have adopted continuous learning, and most assume work leadership roles. The majority acknowledge their fellowship training as having met expectations and uniquely equipping them for their current practice. PMID- 26256936 TI - Surgery vs medical treatment in the management of PFAPA syndrome: a comparative trial. AB - BACKGROUND: Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is a common disorder in children but there is little or no consensus on its optimal diagnosis and management. OBJECTIVES: To compare the outcome of different management approaches - medical therapy or tonsillectomy. METHODS: The medical records of children diagnosed with PFAPA between 2008 and 2013 were retrospectively reviewed according to the modified Thomas test criteria. Patients were divided into two groups: group 1 for medical treatment - corticosteroids, a single intramuscular injection of methylprednisolone, and group 2 for surgery - tonsillectomy alone or tonsillectomy plus adenoidectomy .The course of the disease including the number and duration of episodes and the presence of remission, was documented. RESULTS: 105 patients (30 in group 1, 75 in group 2) met the study's inclusion criteria. Groups 1 and 2 were followed up for a mean (SD) of 23.6 (11.0) and 24 (10.3) months, respectively. At the end of the follow-up period, the number of episodes was 5.8 (6.3) vs 1.8 (1.9) (P<0.01) and their duration was 2.2 (1.3) vs 1.1 (0.8) days (P=0.03), both of which were significantly lower in group 2.The need for hospitalization during this period was significantly lower for group 2 at 1.1 (2.0) vs 0.1 (0.3) (P<0.01) and the remission rate in group 2 was significantly higher than in group 1 (98.6% vs 56.6%, P<0.01). CONCLUSION: This study demonstrated that surgery is superior to medical treatment for PFAPA in terms of increased remission rates and a decrease in the number and duration of episodes. PMID- 26256937 TI - Self-assembled betulinic acid augments immunomodulatory activity associates with IgG response. AB - Studies relating to the adjuvanic role of self assembly, nanosized betulinic acid (SA-BA) are relatively limited. The concept of immunostimulatory activity of SA BA is based on the activation of immune system against cancer antigen. This study showed that SA-BA, a pentacyclic triterpene isolated from the bark of the Ziziphus jujube tree, elevated the immunological functions of cancer antigen in anticancer immunotherapy. We found that, SA-BA pulsed human macrophages secreted elevated level of pro-inflammatory cytokines with an increased CD4(+) cell population. Pulse macrophages were also significantly arrested the KG-1A and K562 cell growth in vitro setup at 1:10 ratio for 48h. The use of TNF-alpha inhibitors confirmed the association between SA-BA with TNF-alpha function. SA-BA pulsed macrophages displayed substantial T cell allostimulatory capacity and promoted the generation of cytotoxic T lymphocytes (CTLs). The adjuvanticity of SA-BA was proved by the generation of in vivo IgG response. Collectively, these findings will enrich the biomedical applications of SA-BA as a potent immune stimulating agent. Moreover, the macrophage stimulating efficacy of SA-BA might be an effective way in the cancer immunotherapy. PMID- 26256938 TI - Liver disease knowledge and acceptability of non-invasive liver fibrosis assessment among people who inject drugs in the drug and alcohol setting: The LiveRLife Study. AB - BACKGROUND: The aim of this study was to assess factors associated with baseline knowledge of HCV and liver disease, acceptability of transient elastography (TE) assessment (FibroScan((r))), and willingness and intent to receive HCV treatment among persons with a history of injection drug use participating in a liver health promotion campaign. METHODS: The LiveRLife campaign involved three phases: (1) campaign resource development; (2) campaign resource testing; and (3) campaign implementation. Participants were enrolled in an observational cohort study with recruitment at four clinics - one primary health care facility, two OST clinics, and one medically supervised injecting centre - in Australia between May and October 2014. Participants received educational material, nurse clinical assessment, TE assessment, dried blood spot testing, and completed a knowledge survey. RESULTS: Of 253 participants (mean age 43 years), 68% were male, 71% had injected in the past month, and 75% self-reported as HCV positive. Median knowledge score was 16/23. In adjusted analysis, less than daily injection (AOR 5.01; 95% CI, 2.64-9.51) and no daily injection in the past month (AOR 3.54; 95% CI, 1.80-6.94) were associated with high knowledge (>=16). TE was the most preferred method both pre- (66%) and post-TE (89%) compared to liver biopsy and blood sample. Eighty-eight percent were 'definitely willing' or 'somewhat willing' to receive HCV treatment, and 56% intended to start treatment in the next 12 months. Approximately 68% had no/mild fibrosis (F0/F1, >=2.5 to <=7.4kPa), 13% moderate fibrosis (F2, >=7.5 to <=9.4kPa), 10% severe fibrosis (F3, >=9.5 to <=12.4kPa), and 9% had cirrhosis (F4, >=12.5kPa). CONCLUSION: Liver disease and HCV knowledge was moderate. High acceptability of TE by PWID provides strong evidence for the inclusion of TE in HCV-related care, and could help to prioritise HCV treatment for those at greatest risk of liver disease progression. PMID- 26256939 TI - A response to Dolliver's "Evaluating drug trafficking on the Tor network". PMID- 26256940 TI - Atorvastatin for the Prophylaxis of Acute Graft-versus-Host Disease in Patients Undergoing HLA-Matched Related Donor Allogeneic Hematopoietic Stem Cell Transplantation (allo-HCT). AB - Statins possess potent immunomodulatory effects that may play a role in preventing acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (allo-HCT). We performed a phase II study of atorvastatin for aGVHD prophylaxis when given to allo-HCT recipients and their HLA-matched sibling donors. Atorvastatin (40 mg/day) was administered to sibling donors, beginning 14 days before the anticipated start of stem cell collection. Allo-HCT recipients (n = 40) received atorvastatin (40 mg/day) in addition to standard aGVHD prophylaxis. The primary endpoint was cumulative incidence of grades II to IV aGVHD at day 100. Atorvastatin was well tolerated, with no attributable grades III to IV toxicities in donors or their recipients. Day 100 and 180 cumulative incidences of grades II to IV aGVHD were 30% (95% confidence interval [CI], 17% to 45%) and 40% (95% CI, 25% to 55%), respectively. One-year cumulative incidence of chronic GVHD was 43% (95% CI, 32% to 69%). One-year nonrelapse mortality and relapse incidences were 5.5% (95% CI, .9% to 16.5%) and 38% (95% CI, 18% to 47%), respectively. One-year progression-free and overall survival rates were 54% (95% CI, 38% to 71%) and 82% (95% CI, 69% to 94%). One-year GVHD-free, relapse-free survival was 27% (95% CI, 16% to 47%). These results did not differ from our historical control subjects (n = 96). Although safe and tolerable, the addition of atorvastatin did not appear to provide any benefit to standard GVHD prophylaxis alone. PMID- 26256941 TI - Indications for Autologous and Allogeneic Hematopoietic Cell Transplantation: Guidelines from the American Society for Blood and Marrow Transplantation. AB - Approximately 20,000 hematopoietic cell transplantation (HCT) procedures are performed in the United States annually. With advances in transplantation technology and supportive care practices, HCT has become safer, and patient survival continues to improve over time. Indications for HCT continue to evolve as research refines the role for HCT in established indications and identifies emerging indications where HCT may be beneficial. The American Society for Blood and Marrow Transplantation (ASBMT) established a multiple-stakeholder task force consisting of transplant experts, payer representatives, and a patient advocate to provide guidance on "routine" indications for HCT. This white paper presents the recommendations from the task force. Indications for HCT were categorized as follows: (1) Standard of care, where indication for HCT is well defined and supported by evidence; (2) Standard of care, clinical evidence available, where large clinical trials and observational studies are not available but HCT has been shown to be effective therapy; (3) Standard of care, rare indication, for rare diseases where HCT has demonstrated effectiveness but large clinical trials and observational studies are not feasible; (4) Developmental, for diseases where preclinical and/or early phase clinical studies show HCT to be a promising treatment option; and (5) Not generally recommended, where available evidence does not support the routine use of HCT. The ASBMT will periodically review these guidelines and will update them as new evidence becomes available. PMID- 26256942 TI - Management of Myelodysplastic Syndrome Relapsing after Allogeneic Hematopoietic Stem Cell Transplantation: A Study by the French Society of Bone Marrow Transplantation and Cell Therapies. AB - To find out prognostic factors and to investigate different therapeutic approaches, we report on 147 consecutive patients who relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS). Sixty-two patients underwent immunotherapy (IT group, second allo-HSCT or donor lymphocyte infusion), 39 received cytoreductive treatment alone (CRT group) and 46 were managed with palliative/supportive cares (PSC group). Two-year rates of overall survival (OS) were 32%, 6%, and 2% in the IT, CRT, and PSC groups, respectively (P < .001). In multivariate analysis, 4 factors adversely influenced 2-year rates of OS: history of acute graft-versus-host disease (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.26 to 2.67; P = .002), relapse within 6 months (HR, 2.69; 95% CI, .82 to 3.98; P < .001), progression to acute myeloid leukemia (HR, 2.59; 95% CI, 1.75 to 3.83; P < .001), and platelet count < 50 G/L at relapse (HR, 1.68; 95% CI, 1.15 to 2.44; P = .007). A prognostic score based on those factors discriminated 2 risk groups with median OSs of 13.2 versus 2.4 months, respectively (P < .001). When propensity score, prognostic score, and treatment strategy were included in Cox model, immunotherapy was found to be an independent factor that favorably impacts OS (HR, .40; 95% CI, .26 to .63; P < .001). In conclusion, immunotherapy should be considered when possible for MDS patients relapsing after allo-HSCT. PMID- 26256943 TI - Hepatitis C Virus Infection among Hematopoietic Cell Transplant Donors and Recipients: American Society for Blood and Marrow Transplantation Task Force Recommendations. PMID- 26256944 TI - Layered gadolinium hydroxides for low-temperature magnetic cooling. AB - Layered gadolinium hydroxides have revealed to be excellent candidates for cryogenic magnetic refrigeration. These materials behave as pure 2D magnetic systems with a Heisenberg-Ising critical crossover, induced by dipolar interactions. This 2D character and the possibility offered by these materials to be delaminated open the possibility of rapid heat dissipation upon substrate deposition. PMID- 26256946 TI - High efficiency air stable organic photovoltaics with an aqueous inorganic contact. AB - We report a ZnO interfacial layer based on an environmentally friendly aqueous precursor for organic photovoltaics. Inverted PCDTBT devices based on this precursor show power conversion efficiencies of 6.8-7%. Unencapsulated devices stored in air display prolonged lifetimes extending over 200 hours with less than 20% drop in efficiency compared to devices based on the standard architecture. PMID- 26256947 TI - Methylisothiazolinone in selected consumer products in Belgium: Adding fuel to the fire? AB - BACKGROUND: Methylisothiazolinone (MI) contact allergy is severely affecting consumers with allergic contact dermatitis, owing to its presence in cosmetics, household detergents, and water-based paints, in particular. Data on the true isothiazolinone concentrations in these products are scarce, and labelling may be incorrect. OBJECTIVES: To report on the MI concentrations in such products marketed in Belgium, in order to verify the accuracy of labelling (when applicable) and compliance with EU regulations. MATERIALS AND METHODS: Thirty cosmetics (18 leave-on and 12 rinse-off), eight detergents and four paints were analysed for MI by the use of high-performance liquid chromatography with ultraviolet detection. RESULTS: The analysed leave-on, and to a lesser extent the rinse-off, cosmetics, contained MI at concentrations far exceeding the permitted 100 ppm use concentration. Household detergents contained high concentrations of MI, and mislabelling occurred for both cosmetics and detergents. The (limited) data on paints are in line with the existing literature. CONCLUSION: Cosmetics and detergents may facilitate contact sensitization because of a (too) high MI concentration, and mislabelling may make its avoidance extremely difficult. Safer use concentrations and correct labelling should be ensured by adequate quality control. PMID- 26256948 TI - Undisclosed methylisothiazolinone in wet wipes for occupational use causing occupational allergic contact dermatitis in a nurse. PMID- 26256949 TI - Hypoxia-mediated cancer stem cells in pseudopalisades with activation of hypoxia inducible factor-1alpha/Akt axis in glioblastoma. AB - Pseudopalisades (Ps) around necrotic foci are severely hypoxic and overexpress hypoxia-inducible factor (HIF) in glioblastoma (GBM). Hypoxic regions have been proposed as one of several distinct niches for cancer stem cells (CSCs) in GBM, but little is known about the association between Ps features and CSC properties. Herein, we focused on the biological role of Ps lesions. In clinical cases of GBM, expression of hypoxia-related molecules including HIF-1alpha, Glut-1, p27(Kip1), and pAkt was significantly increased in perinecrotic Ps lesions compared with nonnecrotic areas and perinecrotic lesions lacking Ps features. Significantly higher expression levels of several CSC-related markers, including CD133, Sox2, CD44s, and aldehyde dehydrogenase (ALDH) 1, were also observed in Ps lesions, which were positively correlated with expression of hypoxia-related molecules and pAkt. Ps lesions also showed increased number of apoptotic cells and decreased bcl-2 and survivin expression compared with the surrounding tissue. Short-term exposure of astrocytoma cell lines to cobalt chloride, which is known to mimic the effect of hypoxia, caused an increase in expression of both hypoxia- and CSC-related markers, in line with increases in the ALDH(high) cell population and number of spheroids. Inhibition of endogenous Akt by LY294002 resulted in decreased expression of Sox2, ALDH1, and CD133, leading to enhancement of cobalt chloride-mediated apoptotic events due to altered ratio of bcl-2 to bax expression. These findings suggest that Ps lesions within GBM may serve as a specialized hypoxic niche, in which the HIF-1alpha/pAkt axis is activated, in response to severe hypoxia. PMID- 26256951 TI - Comparison of cadaveric and isomorphic three-dimensional printed models in temporal bone education. AB - OBJECTIVES/HYPOTHESIS: Current three-dimensional (3D) printed simulations are complicated by insufficient void spaces and inconsistent density. We describe a novel simulation with focus on internal anatomic fidelity and evaluate against template/identical cadaveric education. STUDY DESIGN: Research ethics board approved prospective cohort study. METHODS: Generation of a 3D printed temporal bone was performed using a proprietary algorithm that deconstructs the digital model into slices prior to printing. This supplemental process facilitates removal of residual material from air-containing spaces and permits requisite infiltrative access to the all regions of the model. Ten otolaryngology trainees dissected a cadaveric temporal bone (CTB) followed by a matched/isomorphic 3D printed bone model (PBM), based on derivative micro-computed tomography data. Participants rated 1) physical characteristics, 2) specific anatomic constructs, 3) usefulness in skill development, and 4) perceived educational value. The survey instrument employed a seven-point Likert scale. RESULTS: Trainees felt physical characteristics of the PBM were quite similar to CTB, with highly ranked cortical (5.5 +/- 1.5) and trabecular (5.2 +/- 1.3) bone drill quality. The overall model was considered comparable to CTB (5.9 +/- 0.74), with respectable air cell reproduction (6.1 +/- 1.1). Internal constructs were rated as satisfactory (range, 4.9-6.2). The simulation was considered a beneficial training tool for all types of mastoidectomy (range, 5.9-6.6), posterior tympanotomy (6.5 +/- 0.71), and skull base approaches (range, 6-6.5). Participants believed the model to be an effective training instrument (6.7 +/- 0.68), which should be incorporated into the temporal bone lab (7.0 +/- 0.0). The PBM was thought to improve confidence (6.7 +/- 0.68) and operative performance (6.7 +/- 0.48). CONCLUSIONS: Study participants found the PBM to be an effective platform that compared favorably to CTB. The model was considered a valuable adjunctive training tool with both realistic mechanical and visual character. LEVEL OF EVIDENCE: NA PMID- 26256950 TI - Lysine acetyltransfer supports platelet function. AB - BACKGROUND AND OBJECTIVES: The reversible acetylation of protein lysine epsilon amino groups, catalyzed by lysine acetyltransferases and deacetylases, serves as a molecular switch in the orchestration of diverse cellular activities. Here, we aimed to investigate the role of lysine acetyltransfer in platelet function. METHODS AND RESULTS: Proteomics methods identified 552 acetyllysine (acK) modifications on 273 platelet proteins that serve as candidate substrates for lysine acetyltransferases. Bioinformatics analyses of the identified acK-modified platelet proteins supported roles for the lysine acetyltransferase p300 in the regulation of actin-mediated platelet processes. Biochemical experiments showed that platelets express p300, which is activated in an Src kinase-dependent manner upon platelet stimulation with the platelet glycoprotein VI agonist collagen related peptide (CRP). Inhibition of platelet p300 abrogated CRP-stimulated lysine acetylation of actin, filamin, and cortactin, as well as F-actin polymerization, integrin activation, and platelet aggregation. Super-resolution visualization of platelet actin-rich adhesion structures revealed abundant acK protein colocalized with platelet actin cytoskeletal proteins. Inhibition of p300 blocked platelet filopodium formation and the spreading of platelets on fibrinogen and collagen surfaces. In whole blood, p300 inhibition prevented the formation of platelet aggregates under shear, suggesting a physiologic role for lysine acetyltransferase activity in platelet function. CONCLUSION: Together, our findings reveal lysine acetyltransfer to be a potential regulator of platelet actin dynamics, and potential roles for lysine acetylation in the molecular coordination of platelet activation and function. PMID- 26256952 TI - Targeting oxidative stress to treat endometriosis. AB - INTRODUCTION: Endometriosis affects 10% of women of reproductive age. It is defined as the presence of implanted active endometrial tissue outside the uterine cavity. The exact pathophysiology of endometriosis is still uncertain, although several optional etiological theories have been suggested. Being so common, a novel treatment for endometriosis is widely quested. Recent studies addressing the pathological characteristics of endometriosis have revealed a vicious cycle in which oxidative stress (OS) is generated, which in turn facilitates the implantation of the ectopic endometrium. At the same time, the generation of high amounts of reactive oxygen species further triggers a state of OS. AREAS COVERED: The author examined the evidence associating OS and endometriosis. After establishing an association, a search for antioxidant agents that were investigated specifically on endometriosis patients are described including Vitamins C and E, melatonin, resveratrol, xanthohumol and epigallocatechin-3-gallate. A significant effect of all the reviewed antioxidants on endometriosis is reported. EXPERT OPINION: Aiming for the reduction of OS as the treatment goal for endometriosis looks promising. However, since most of the studies are either in vitro or are animal based, further studies on human subjects are deemed necessary to elucidate the impact of OS reduction on patients with endometriosis. PMID- 26256953 TI - Half-metallic and magnetic properties in nonmagnetic element embedded graphitic carbon nitride sheets. AB - We have investigated the structures, electronic structures and magnetic properties of the triazine-based g-C3N4 (gt-C3N4) monolayer doped with B, Al, and Cu atoms based on density functional theory using ab initio calculations. The B atom prefers to be situated at the center of the triazine ring, whereas the Al and Cu atoms tend to be located above the center of the triazine ring. The doping at the interstitial sites results in nonplanar structures which are thermodynamically stable. Each dopant atom induces a total magnetic moment of 1.0 MUB which mainly arises from the pz orbitals because the n-type doping injects unpaired electrons into anti-pi orbitals. The results obtained from the GGA-PBE and HSE06 schemes show that all the doped systems exhibit half-metallic behaviors. B- and Al-doped systems are at a ferromagnetic ground state, while the Cu-doped case is at an anti-ferromagnetic ground state. The long-range half metallic ferromagnetic order is attributed to the p-p interactions. In particular, the estimated Curie temperature implies that the systems doped with B are potential candidates for spintronics applications in future. PMID- 26256954 TI - Diatom silica biomineralization: Parallel development of approaches and understanding. AB - Diatom silica cell walls present an intriguing application of biomineralization in a single celled organism. The ability of diatoms to make an enormous variety of silica structures on the nano- to micro-scale is unparalleled in nature. The process is a whole-cell endeavor, involving diverse cellular components that coordinate "bottom up" and "top down" structure formation processes to reproducibly convert genetic information into physical structure. The study of silicification has been similarly all encompassing, involving the application of diverse analytical techniques to examine different aspects of the process. This review highlights the application of different approaches used to study silicification and the insights they have provided, and documents the progress that has been made. The current status offers the possibility of major breakthroughs in our understanding, by enabling a more widespread identification of genes involved, and direct testing of the role these genes play by genetic manipulation. PMID- 26256956 TI - The First Fellow of American College of Surgeons to Come to Korea: Dr. Alfred Irving Ludlow. PMID- 26256955 TI - Mechanics of tissue compaction. AB - During embryonic development, tissues deform by a succession and combination of morphogenetic processes. Tissue compaction is the morphogenetic process by which a tissue adopts a tighter structure. Recent studies characterized the respective roles of cells' adhesive and contractile properties in tissue compaction. In this review, we formalize the mechanical and molecular principles of tissue compaction and we analyze through the prism of this framework several morphogenetic events: the compaction of the early mouse embryo, the formation of the fly retina, the segmentation of somites and the separation of germ layers during gastrulation. PMID- 26256957 TI - An Outbreak of Middle East Respiratory Syndrome Coronavirus Infection in South Korea, 2015. PMID- 26256958 TI - Evolution of Gastric Cancer Treatment: From the Golden Age of Surgery to an Era of Precision Medicine. AB - Gastric cancer imposes a global health burden. Although multimodal therapies have proven to benefit patients with advanced diseases after curative surgery, the prognosis of most advanced cancer patients still needs to be improved. Surgical extirpation is the mainstay of gastric cancer treatment. Indeed, without curative surgery, variations and combinations of chemotherapy and/or radiation cannot bring clinically meaningful success. Centered around D2 surgery, adjuvant and peri-operative multimodal therapies have improved survival in a certain group of gastric cancer patients. Moving toward a personalized cancer therapy era, molecular targeted strategies have been tested in clinical trials for gastric cancer. With some success and failures, we have learned valuable lessons regarding the biology of gastric cancer and the clinical relevance of biological therapies in addition to conventional treatments. Future treatment of gastric cancer will be shifted to molecularly tailored and genome information-based personalized therapy. Collaboration across disciplines and actively adopting emerging anti-cancer strategies, along with in-depth understanding of molecular and genetic underpinnings of tumor development and progression, are imperative to realizing personalized therapy for gastric cancer. Although many challenges remain to be overcome, we envision that the era of precision cancer medicine for gastric cancer has already arrived and anticipate that current knowledge and discoveries will be transformed into near-future clinical practice for managing gastric cancer patients. PMID- 26256960 TI - Outcome and Complications in Surgical Treatment of Lumbar Stenosis or Spondylolisthesis in Geriatric Patients. AB - Development of anesthesiology and improvement of surgical instruments enabled aggressive surgical treatment even in elderly patients, who require more active physical activities than they were in the past. However, there are controversies about the clinical outcome of spinal surgery in elderly patients with spinal stenosis or spondylolisthesis. The purpose of this study is to review the clinical outcome of spinal surgery in elderly patients with spinal stenosis or spondylolisthesis. MEDLINE search on English-language articles was performed. There were 39685 articles from 1967 to 2013 regarding spinal disease, among which 70 dealt with geriatric lumbar surgery. Eighteen out of 70 articles dealt with geriatric lumbar surgery under the diagnosis of spinal stenosis or spondylolisthesis. One was non-randomized prospective, and other seventeen reports were retrospective. One non-randomized prospective and twelve out of seventeen retrospective studies showed that old ages did not affect the clinical outcomes. One non-randomized prospective and ten of seventeen retrospective studies elucidated postoperative complications: some reports showed that postoperative complications increased in elderly patients, whereas the other reports showed that they did not increase. Nevertheless, most complications were minor. There were two retrospective studies regarding the mortality. Mortality which was unrelated to surgical procedure increased, but surgical procedure related mortality did not increase. Surgery as a treatment option in the elderly patients with the spinal stenosis or spondylolisthesis may be reasonable. However, there is insufficient evidence to make strong recommendations regarding spinal surgery for geriatric patients with spinal stenosis and spondylolisthesis. PMID- 26256959 TI - Cancer Cell Line Panels Empower Genomics-Based Discovery of Precision Cancer Medicine. AB - Since the first human cancer cell line, HeLa, was established in the early 1950s, there has been a steady increase in the number and tumor type of available cancer cell line models. Cancer cell lines have made significant contributions to the development of various chemotherapeutic agents. Recent advances in multi-omics technologies have facilitated detailed characterizations of the genomic, transcriptomic, proteomic, and epigenomic profiles of these cancer cell lines. An increasing number of studies employ the power of a cancer cell line panel to provide predictive biomarkers for targeted and cytotoxic agents, including those that are already used in clinical practice. Different types of statistical and machine learning algorithms have been developed to analyze the large-scale data sets that have been produced. However, much work remains to address the discrepancies in drug assay results from different platforms and the frequent failures to translate discoveries from cell line models to the clinic. Nevertheless, continuous expansion of cancer cell line panels should provide unprecedented opportunities to identify new candidate targeted therapies, particularly for the so-called "dark matter" group of cancers, for which pharmacologically tractable driver mutations have not been identified. PMID- 26256961 TI - Prognostic Impacts of Metastatic Site and Pain on Progression to Castrate Resistance and Mortality in Patients with Metastatic Prostate Cancer. AB - PURPOSE: To investigate predictors of progression to castration-resistant prostate cancer (CRPC) and cancer-specific mortality (CSM) in patients with metastatic prostate cancer (mPCa). MATERIALS AND METHODS: A retrospective analysis was performed on 440 consecutive treatment-naive patients initially diagnosed with mPCa between August 2000 and June 2012. Patient age, body mass index (BMI), Gleason score, prostate-specific antigen (PSA), PSA nadir, American Joint Committee on Cancer stage, Visual Analogue Scale pain score, Eastern Cooperative Oncology Group performance score (ECOG PS), PSA response to hormone therapy, and metastatic sites were assessed. Cox-proportional hazards regression analyses were used to evaluate survivals and predictive variables of men with bone metastasis stratified according to the presence of pain, compared to men with visceral metastasis. RESULTS: Metastases were most often found in bone (75.4%), followed by lung (16.3%) and liver (8.3%) tissues. Bone metastasis, pain, and high BMI were associated with increased risks of progression to CRPC, and bone metastasis, pain, PSA nadir, and ECOG PS>=1 were significant predictors of CSM. During the median follow-up of 32.0 (interquartile range 14.7-55.9) months, patients with bone metastasis with pain and patients with both bone and visceral metastases showed the worst median progression to CRPC-free and cancer specific survivals, followed by men with bone metastasis without pain. Patients with visceral metastasis had the best median survivals. CONCLUSION: Metastatic spread and pain patterns confer different prognosis in patients with mPCa. Bone may serve as a crucial microenvironment in the development of CRPC and disease progression. PMID- 26256962 TI - Characteristics and Survival of Breast Cancer Patients with Multiple Synchronous or Metachronous Primary Cancers. AB - PURPOSE: Newly developed extra-mammary multiple primary cancers (MPCs) are an issue of concern when considering the management of breast cancer survivors. This study aimed to investigate the prevalence of MPCs and to evaluate the implications of MPCs on the survival of breast cancer patients. MATERIALS AND METHODS: A total of 8204 patients who underwent surgery at Severance Hospital between 1990 and 2012 were retrospectively selected. Clinicopathologic features and survival over follow-up periods of <=5 and >5 years were investigated using univariate and multivariate analyses. RESULTS: During a mean follow-up of 67.3 months, 962 MPCs in 858 patients (10.5%) were detected. Synchronous and metachronous MPCs were identified in 23.8% and 79.0% of patients, respectively. Thyroid cancer was the most prevalent, and the second most common was gynecologic cancer. At <=5 years, patients with MPCs were older and demonstrated significantly worse survival despite a higher proportion of patients with lower stage MPCs. Nevertheless, an increased risk of death in patients with MPCs did not reach statistical significance at >5 years. The causes of death in many of the patients with MPCs were not related to breast cancer. Stage-matched analysis revealed that the implications of MPCs on survival were more evident in the early stages of breast disease. CONCLUSION: Breast cancer patients with MPCs showed worse survival, especially when early-stage disease was identified. Therefore, it is necessary to follow screening programs in breast cancer survivors and to establish guidelines for improving prognosis and quality of life. PMID- 26256963 TI - Analysis of Dysphagia Patterns Using a Modified Barium Swallowing Test Following Treatment of Head and Neck Cancer. AB - PURPOSE: The purposes of this study were to evaluate specific dysphagia patterns and to identify the factors affecting dysphagia, especially aspiration, following treatment of head and neck cancer. MATERIALS AND METHODS: A retrospective analysis of 57 patients was performed. Dysphagia was evaluated using a modified barium swallow (MBS) test. The MBS results were rated on the 8-point penetration aspiration scale (PAS) and swallowing performance status (SPS) score. RESULTS: Reduced base of the tongue (BOT) retraction (64.9%), reduced laryngeal elevation (57.9%), and cricopharyngeus (CP) dysfunction (47.4%) were found. Reduced BOT retraction was correlated with clinical stage (p=0.011) and treatment modality (p=0.001). Aspiration in 42.1% and penetration in 33.3% of patients were observed. Twenty-four patients had PAS values over 6, implying aspiration. Forty one patients had a SPS score of more than 3, 25 patients had a score greater than 5, and 13 patients had a SPS score of more than 7. Aspiration was found more often in patients with penetration (p=0.002) and in older patients (p=0.026). In older patients, abnormal swallowing caused aspiration even in those with a SPS score of more than 3, irrespective of stage or treatment, contrary to younger patients. Tube feeders (n=20) exhibited older age (65.0%), dysphagia/aspiration related structures (DARS) primaries (75.0%), higher stage disease (66.7%), and a history of radiotherapy (68.8%). CONCLUSION: Reduced BOT retraction was the most common dysphagia pattern and was correlated with clinical stage and treatment regimens including radiotherapy. Aspiration was more frequent in patients who had penetration and in older patients. In contrast to younger patients, older patients showed greater risk of aspiration even with a single abnormal swallowing irrespective of stage or treatment. PMID- 26256964 TI - Effect of Triflusal on Primary Vascular Dysregulation Compared with Aspirin: A Double-Blind, Randomized, Crossover Trial. AB - PURPOSE: Primary vascular dysregulation (PVD) is a condition in which the response to cold temperature or external stimuli is abnormal. We investigated whether triflusal use results in amelioration of PVD symptoms and improvement of several related parameters compared with aspirin. MATERIALS AND METHODS: Eighty eight PVD patients (54% female, 56+/-8 years) were randomly selected to receive either triflusal (300 mg, b.i.d.) or aspirin (150 mg, b.i.d.) for a period of 6 weeks followed by crossover. PVD was defined as both red-blood-cell standstill in video-assisted microscopic capillaroscopy during cold stimulation using carbon dioxide gas and a score of more than 7 points in a validated questionnaire. Efficacy of treatment was assessed by 1) cold intolerance symptom severity (CISS) score, 2) finger Doppler indices, and 3) indocyanine green perfusion imaging. RESULTS: The use of triflusal resulted in a greater improvement in CISS score (44.5+/-18.4 vs. 51.9+/-16.2; p<0.001) and in mean radial peak systolic velocity (69.8+/-17.2 vs. 66.1+/-16.4; p=0.011) compared to aspirin. Furthermore, significant differences were also observed in perfusion rates on indocyanine green perfusion imaging between triflusal and aspirin (45.6+/-25.8 vs. 51.6+/ 26.9; p=0.020). CONCLUSION: Triflusal was more effective and demonstrated a more consistent impact on the improvement of symptoms and blood flow in patients with PVD than aspirin. PMID- 26256965 TI - Clinical and Angiographic Predictors of Microvascular Dysfunction in ST-Segment Elevation Myocardial Infarction. AB - PURPOSE: We aimed to discover clinical and angiographic predictors of microvascular dysfunction using the index of microcirculatory resistance (IMR) in patients with ST-segment elevation myocardial infarction (STEMI). MATERIALS AND METHODS: We enrolled 113 patients with STEMI (age, 56+/-11 years; 95 men) who underwent primary percutaneous coronary intervention (PCI). The IMR was measured with a pressure sensor/thermistor-tipped guidewire after primary PCI. The patients were divided into three groups based on IMR values: Low IMR [<18 U (12.9+/-2.6 U), n=38], Mid IMR [18-31 U (23.9+/-4.0 U), n=38], and High IMR [>31 U (48.1+/-17.1 U), n=37]. RESULTS: The age of the Low IMR group was significantly lower than that of the Mid and High IMR groups. The door-to-balloon time was <90 minutes in all patients, and it was not significantly different between groups. Meanwhile, the symptom-onset-to-balloon time was significantly longer in the High IMR group, compared to the Mid and Low IMR groups (p<0.001). In the high IMR group, the culprit lesion was found in a proximal location significantly more often than in a non-proximal location (p=0.008). In multivariate regression analysis, age and symptom-onset-to-balloon time were independent determinants of a high IMR (p=0.013 and p=0.003, respectively). CONCLUSION: Our data suggest that age and symptom-onset-to-balloon time might be the major predictors of microvascular dysfunction in STEMI patients with a door-to-balloon time of <90 minutes. PMID- 26256966 TI - eNOS3 Genetic Polymorphism Is Related to Post-Ablation Early Recurrence of Atrial Fibrillation. AB - PURPOSE: Previous studies have demonstrated an association between eNOS polymorphisms and atrial fibrillation (AF). We sought to determine whether eNOS polymorphisms are associated with AF recurrence after a radiofrequency catheter ablation (RFCA). MATERIALS AND METHODS: A total of 500 consecutive patients (56+/ 11 years, 77% male) with paroxysmal (68%) or persistent (32%) AF who underwent RFCA and 500 age, gender-matched controls were genotyped for the eNOS3 single nucleotide polymorphism (rs1799983). AF recurrence was monitored according to 2012 ACC/AHA/ESC guidelines. RESULTS: The frequencies of the rs1799983 variant alleles (T) in the case and control group were not significantly different (OR 1.05, 95% CI 0.75-1.46, p=0.798). AF patients with rs1799983 variants were more likely to have coronary artery disease or stroke than those without genetic variant at this gene (31.0% vs. 17.3%, p=0.004). During mean 17 months follow-up, early recurrence of AF (ERAF; within 3 months) and clinical recurrence (CR) of AF were 31.8% and 24.8%, respectively. The rs1799983 variant was associated with higher risk of ERAF (OR 1.71, 95% CI 1.06-2.79, p=0.028), but not with CR. ERAF occurred earlier (11+/-16 days) in variant group than those without variant allele (20+/-25 days, p=0.016). A multiple logistic regression analysis showed that presence of the rs1799983 variant (OR 1.75, 95% CI 1.07-2.86, p=0.026) and persistent AF were independent predictors for ERAF after AF ablation. CONCLUSION: The rs1799983 variant of the eNOS3 gene was associated with ERAF, but not with CR, after RFCA. eNOS3 gene variants may have a potential role for stratification of post-ablation management. PMID- 26256967 TI - In silico Screening of Chemical Libraries to Develop Inhibitors That Hamper the Interaction of PCSK9 with the LDL Receptor. AB - PURPOSE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low density lipoprotein receptor (LDLR) and promotes degradation of the LDLR. Inhibition of PCSK9 either by reducing its expression or by blocking its activity results in the upregulation of the LDLR and subsequently lowers the plasma concentration of LDL-cholesterol. As a modality to inhibit PCSK9 action, we searched the chemical library for small molecules that block the binding of PCSK9 to the LDLR. MATERIALS AND METHODS: We selected 100 chemicals that bind to PCSK9 where the EGF-AB fragment of the LDLR binds via in silico screening of the ChemBridge chemical library, using the computational GOLD algorithm analysis. Effects of chemicals were evaluated using the PCSK9-LDLR binding assay, immunoblot analysis, and the LDL-cholesterol uptake assay in vitro, as well as the fast performance liquid chromatography assay for plasma lipoproteins in vivo. RESULTS: A set of chemicals were found that decreased the binding of PCSK9 to the EGF-AB fragment of the LDLR in a dose-dependent manner. They also increased the amount of the LDLR significantly and subsequently increased the uptake of fluorescence-labeled LDL in HepG2 cells. Additionally, one particular molecule lowered the plasma concentration of total cholesterol and LDL-cholesterol significantly in wild-type mice, while such an effect was not observed in Pcsk9 knockout mice. CONCLUSION: Our findings strongly suggest that in silico screening of small molecules that inhibit the protein-protein interaction between PCSK9 and the LDLR is a potential modality for developing hypercholesterolemia therapeutics. PMID- 26256969 TI - Comparison of Second- and Third-Generation Cephalosporin as Initial Therapy for Women with Community-Onset Uncomplicated Acute Pyelonephritis. AB - PURPOSE: This study examined the clinical effectiveness of parenteral cefuroxime and cefotaxime as empirical antibiotics for treating hospitalized women with uncomplicated acute pyelonephritis (APN). MATERIALS AND METHODS: This study was based on the clinical and microbiologic data of 255 hospitalized women with APN. Of these 255 women, 144 patients received cefuroxime and 111 received cefotaxime. RESULTS: There were no marked differences in the demographic features, clinical characteristics, and treatment duration between the populations of the cefuroxime and cefotaxime groups. The rates of defervescence showed no significant differences in the two groups at 48, 72, 96, and 120 hours. The clinical cure rates observed at the follow-up visit 4 to 14 days after the completion of antimicrobial therapy were not statistically different between the cefuroxime and cefotaxime groups [94.9% (129 of 136) versus 98.0% (100 of 102), respectively; p=0.307], and the microbiological cure rates were also not significantly different [88.3% (91 of 103) versus 95.0% (76 of 80), respectively; p=0.186]. The median hospitalization periods in the cefuroxime and cefotaxime groups were 7 (6 8) and 7 (6-8) days (p=0.157), respectively. Microbiological success rates after 72-96 hours of initial antimicrobial therapy were also not statistically different in the cefuroxime and cefotaxime groups, 89.4% (110 of 123) versus 94.9% (93 of 98; p=0.140). CONCLUSION: Cefuroxime, a second-generation cephalosporin, is an appropriate antibiotic option for the initial treatment of uncomplicated APN and its efficacy does not differ from cefotaxime, a third generation cephalosporin, in the initial parenteral therapy for community-onset APN. PMID- 26256968 TI - Clinical Features of Obstructive Sleep Apnea That Determine Its High Prevalence in Resistant Hypertension. AB - PURPOSE: Resistant hypertension (HTN) occurs in 15-20% of treated hypertensive patients, and 70-80% of resistant hypertensive patients have obstructive sleep apnea (OSA). The characteristics of resistant HTN that predispose patients to OSA have not been reported. Therefore, we aimed to determine the clinical, laboratory, and polysomnographic features of resistant HTN that are significantly associated with OSA. MATERIALS AND METHODS: Hypertensive patients (n=475) who underwent portable polysomnography were enrolled. The patients were categorized into controlled (n=410) and resistant HTN (n=65) groups. The risk factors for the occurrence of OSA in controlled and resistant hypertensive patients were compared, and independent risk factors that are associated with OSA were analyzed. RESULTS: Out of 475 patients, 359 (75.6%) were diagnosed with OSA. The prevalence of OSA in resistant HTN was 87.7%, which was significantly higher than that in controlled HTN (73.7%). Age, body mass index, neck circumference, waist circumference, and hip circumference were significantly higher in OSA. However, stepwise multivariate analyses revealed that resistant HTN was not an independent risk factor of OSA. CONCLUSION: The higher prevalence and severity of OSA in resistant HTN may be due to the association of risk factors that are common to both conditions. PMID- 26256970 TI - IL-10 Polymorphisms and Tuberculosis Susceptibility: An Updated Meta-Analysis. AB - PURPOSE: The association of interleukin-10 (IL-10) polymorphisms (-1082G/A, 819C/T, -592A/C) and interleukin-6 (IL-6) poly-morphisms (-174G/C) with tuberculosis (TB) risk has been widely reported. However, the results are controversial. To clarify the role of these polymorphisms in TB, we performed a meta-analysis of all available and relevant published studies. MATERIALS AND METHODS: Based on comprehensive searches of the PubMed, Medline, Embase, Web of Science, Elsevier Science Direct and Cochrane Library database, we identified outcome data from all articles estimating the association between IL-10 and IL-6 polymorphisms and TB risk. RESULTS: The results indicated significant association of the allele model, heterozygous model and dominant model of IL-6 -174G/C polymorphism with decreased risk of TB. In the stratified analysis by ethnicity, significantly increased risk was observed for IL-10 -1082G/A polymorphism in Europeans under recessive model, for IL-10 -819C/T polymorphism in Asians under heterozygous model and dominant model and IL-10 -592A/C polymorphism in Asians under Allele model, homozygous model and recessive model. Moreover, significantly decreased risk of TB was associated with Asians for IL-6 -174C/G polymorphism in allele model, heterozygous model and dominant model. We also performed the analyses by sample types in IL-10 -1082G/A polymorphism, and observed significantly increased TB risk in mixed group under homozygous model. CONCLUSION: The results suggested that the IL-10 -1082G/A polymorphism is associated with increased TB risk in Europeans, while IL-10 -819C/T and IL-10 592A/C polymorphisms in Asians. However, IL-6 -174G/C polymorphism might be a genetic risk factor that decreases TB susceptibility in Asians. PMID- 26256971 TI - Nonalcoholic Fatty Liver Disease Is Associated with the Presence and Morphology of Subclinical Coronary Atherosclerosis. AB - PURPOSE: In this study, we aimed to evaluate whether nonalcoholic fatty liver disease (NAFLD) was associated with the presence and morphology of coronary atherosclerotic plaques shown by multidetector computed tomography (MDCT) in asymptomatic subjects without a history of cardiovascular disease. MATERIALS AND METHODS: We retrospectively enrolled 772 consecutive South Korean individuals who had undergone both dualsource 64-slice MDCT coronary angiography and hepatic ultrasonography during general routine health evaluations. The MDCT studies were assessed for the presence, morphology (calcified, mixed, and non-calcified), and severity of coronary plaques. RESULTS: Coronary atherosclerotic plaques were detected in 316 subjects (40.9%) by MDCT, and NAFLD was found in 346 subjects (44.8%) by hepatic ultrasonography. Subjects with NAFLD had higher prevalences of all types of atherosclerotic plaque and non-calcified, mixed, and calcified plaques than the subjects without NAFLD. However, the prevalence of significant stenosis did not differ between groups. After adjusting for age, smoking status, diabetes mellitus, hypertension, dyslipidemia, and metabolic syndrome, NAFLD remained a significant predictor for all types of coronary atherosclerotic plaque [odds ratio (OR): 1.48; 95% confidence interval (CI): 1.05-2.08; p=0.025] in binary logistic analysis, as well as for calcified plaques (OR: 1.70; 95% CI: 1.07-2.70; p=0.025) in multinomial regression analysis. CONCLUSION: Our study demonstrated that NAFLD was significantly associated with the presence and the calcified morphology of coronary atherosclerotic plaques detected by MDCT. Further prospective clinical studies are needed to clarify the exact physiopathologic role of NAFLD in coronary atherosclerosis. PMID- 26256972 TI - Serum Dickkopf-1 as a Biomarker for the Diagnosis of Hepatocellular Carcinoma. AB - PURPOSE: Dickkopf-1 (DKK-1) is a Wnt/beta-catenin signaling pathway inhibitor. We investigated whether DKK-1 is related to progression in hepatocellular carcinoma (HCC) cells and HCC patients. MATERIALS AND METHODS: In vitro reverse transcription polymerase chain reaction (RT-PCR), wound healing assays, invasion assays, and ELISAs of patient serum samples were employed. The diagnostic accuracy of the serum DKK-1 ELISA was assessed using receiver operating characteristic (ROC) curves and area under ROC (AUC) analyses. RESULTS: RT-PCR showed high DKK-1 expression in Hep3B and low in 293 cells. Similarly, the secreted DKK-1 concentration in the culture media was high in Hep3B and low in 293 cells. Wound healing and invasion assays using 293, Huh7, and Hep3B cells showed that DKK-1 overexpression promoted cell migration and invasion, whereas DKK-1 knock-down inhibited them. When serum DKK-1 levels were assessed in 370 participants (217 with HCC and 153 without), it was significantly higher in HCC patients than in control groups (median 1.48 ng/mL vs. 0.90 ng/mL, p<0.001). The optimum DKK-1 cutoff level was 1.01 ng/mL (AUC=0.829; sensitivity 90.7%; specificity 62.0%). Although DKK-1 had a higher AUC than alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) (AUC=0.829 vs. 0.794 and 0.815, respectively), they were statistically similar (all p>0.05). When three biomarkers were combined (DKK-1 plus AFP plus DCP), they showed significantly higher AUC (AUC=0.952) than single marker, DKK-1 plus AFP, or DKK-1 plus DCP (all p<0.001). CONCLUSION: DKK-1 might be a key regulator in HCC progression and a potential therapeutic target in HCC. Serum DKK-1 could complement the diagnostic accuracy of AFP and DCP. PMID- 26256973 TI - TWIK-Related Spinal Cord K+ Channel Expression Is Increased in the Spinal Dorsal Horn after Spinal Nerve Ligation. AB - PURPOSE: The TWIK-related spinal cord K+ channel (TRESK) has recently been discovered and plays an important role in nociceptor excitability in the pain pathway. Because there have been no reports on the TRESK expression or its function in the dorsal horn of the spinal cord in neuropathic pain, we analyzed TRESK expression in the spinal dorsal horn in a spinal nerve ligation (SNL) model. MATERIALS AND METHODS: We established a SNL mouse model by using the L5-6 spinal nerves ligation. We used real-time polymerase chain reaction and immunohistochemistry to investigate TRESK expression in the dorsal horn and L5 dorsal rot ganglion (DRG). RESULTS: The SNL group showed significantly higher expression of TRESK in the ipsilateral dorsal horn under pain, but low expression in L5 DRG. Double immunofluorescence staining revealed that immunoreactivity of TRESK was mostly restricted in neuronal cells, and that synapse markers GAD67 and VGlut2 appeared to be associated with TRESK expression. We were unable to find a significant association between TRESK and calcineurin by double immunofluorescence. CONCLUSION: TRESK in spinal cord neurons may contribute to the development of neuropathic pain following injury. PMID- 26256974 TI - Effect of Subthalamic Deep Brain Stimulation on Levodopa-Induced Dyskinesia in Parkinson's Disease. AB - PURPOSE: To evaluate the effect of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) on levodopa-induced peak-dose dyskinesia in patients with Parkinson's disease (PD). MATERIALS AND METHODS: A retrospective review was conducted on patients who underwent STN DBS for PD from May 2000 to July 2012. Only patients with levodopa-induced dyskinesia prior to surgery and more than 1 year of available follow-up data after DBS were included. The outcome measures included the dyskinesia subscore of the Unified Parkinson's Disease Rating Scale (UPDRS) part IV (items 32 to 34 of UPDRS part IV) and the levodopa equivalent daily dose (LEDD). The patients were divided into two groups based on preoperative to postoperative LEDD change at 12 months after the surgery: Group 1, LEDD decrease >15%; Group 2, all other patients. Group 2 was further divided by the location of DBS leads. RESULTS: Of the 100 patients enrolled, 67 were in Group 1, while those remaining were in Group 2. Twelve months after STN DBS, Groups 1 and 2 showed improvements of 61.90% and 57.14%, respectively, in the dyskinesia subscore. Group 1 was more likely to experience dyskinesia suppression; however, the association between the groups and dyskinesia suppression was not statistically significant (p=0.619). In Group 2, dyskinesia was significantly decreased by stimulation of the area above the STN in 18 patients compared to stimulation of the STN in 15 patients (p=0.048). CONCLUSION: Levodopa-induced dyskinesia is attenuated by STN DBS without reducing the levodopa dosage. PMID- 26256975 TI - Ivy Sign on Fluid-Attenuated Inversion Recovery Images in Moyamoya Disease: Correlation with Clinical Severity and Old Brain Lesions. AB - PURPOSE: Leptomeningeal collateral, in moyamoya disease (MMD), appears as an ivy sign on fluid-attenuated inversion-recovery (FLAIR) images. There has been little investigation into the relationship between presentation of ivy signs and old brain lesions. We aimed to evaluate clinical significance of ivy signs and whether they correlate with old brain lesions and the severity of clinical symptoms in patients with MMD. MATERIALS AND METHODS: FLAIR images of 83 patients were reviewed. Each cerebral hemisphere was divided into 4 regions and each region was scored based on the prominence of the ivy sign. Total ivy score (TIS) was defined as the sum of the scores from the eight regions and dominant hemispheric ivy sign (DHI) was determined by comparing the ivy scores from each hemisphere. According to the degree of ischemic symptoms, patients were classified into four subgroups: 1) nonspecific symptoms without motor weakness, 2) single transient ischemic attack (TIA), 3) recurrent TIA, or 4) complete stroke. RESULTS: TIS was significantly different as follows: 4.86+/-2.55 in patients with nonspecific symptoms, 5.89+/-3.10 in patients with single TIA, 9.60+/-3.98 in patients with recurrent TIA and 8.37+/-3.39 in patients with complete stroke (p=0.003). TIS associated with old lesions was significantly higher than those not associated with old lesions (9.35+/-4.22 vs. 7.49+/-3.37, p=0.032). We found a significant correlation between DHI and motor symptoms (p=0.001). CONCLUSION: Because TIS has a strong tendency with severity of ischemic motor symptom and the presence of old lesions, the ivy sign may be useful in predicting severity of disease progression. PMID- 26256976 TI - Influence of Parent Artery Segmentation and Boundary Conditions on Hemodynamic Characteristics of Intracranial Aneurysms. AB - PURPOSE: The purpose of this study is to explore the influence of segmentation of the upstream and downstream parent artery and hemodynamic boundary conditions (BCs) on the evaluated hemodynamic factors for the computational fluid dynamics (CFD) analysis of intracranial aneurysms. MATERIALS AND METHODS: Three dimensional patient-specific aneurysm models were analyzed by applying various combinations of inlet and outlet BCs. Hemodynamic factors such as velocity pattern, streamline, wall shear stress, and oscillatory shear index at the systolic time were visualized and compared among the different cases. RESULTS: Hemodynamic factors were significantly affected by the inlet BCs while there was little influence of the outlet BCs. When the inlet length was relatively short, different inlet BCs showed different hemodynamic factors and the calculated hemodynamic factors were also dependent on the inlet length. However, when the inlet length (L) was long enough (L>20D, where D is the diameter of inlet section), the hemodynamic factors became similar regardless of the inlet BCs and lengths. The error due to different inlet BCs was negligible. The effect of the outlet length on the hemodynamic factors was similar to that of the inlet length. CONCLUSION: Simulated hemodynamic factors are highly sensitive to inlet BCs and upstream parent artery segmentation. The results of this work can provide an insight into how to build models and to apply BCs for more accurate estimation of hemodynamic factors from CFD simulations of intracranial aneurysms. PMID- 26256977 TI - Focal Lymphocytic Thyroiditis Nodules Share the Features of Papillary Thyroid Cancer on Ultrasound. AB - PURPOSE: It is often difficult to discriminate focal lymphocytic thyroiditis (FLT) or adenomatous hyperplasia (AH) from thyroid cancer if they both have suspicious ultrasound (US) findings. We aimed to make a predictive model of FLT from papillary thyroid cancer (PTC) in suspicious nodules with benign cytologic results. MATERIALS AND METHODS: We evaluated 214 patients who had undergone fine needle aspiration biopsy (FNAB) and had shown thyroid nodules with suspicious US features. PTC was confirmed by surgical pathology. FLT and AH were confirmed through more than two separate FNABs. Clinical and biochemical findings, as well as US features, were evaluated. RESULTS: Of 214 patients, 100 patients were diagnosed with PTC, 55 patients with FLT, and 59 patients with AH. The proportion of elevated thyrotropin (TSH) levels (p=0.014) and thyroglobulin antibody (Tg-Ab) or thyroid peroxidase antibody (TPO-Ab) positivity (p<0.001) in the FLT group was significantly higher than that in the PTC group. Regarding US features, absence of calcification (p=0.006) and "diffuse thyroid disease" (DTD) pattern on US (p<0.001) were frequently seen in the FLT group. On multivariate analysis, Tg-Ab positivity, presence of a DTD pattern on US, and absence of calcification in nodules were associated with FLT with the best specificity of 99% and positive predictive value of 96%. In contrast, a taller than wide shape of nodules was the only variable significant for differentiating AH from PTC. CONCLUSION: Suspicious thyroid nodules with cytologic benign results could be followed up with US rather than repeat FNAB, if patients exhibit Tg-Ab positivity, no calcifications in nodules, and a DTD pattern on US. PMID- 26256978 TI - Image Settings Affecting Nuchal Translucency Measurement Using Volume NT Software. AB - PURPOSE: To evaluate the effects of the deviation from the mid-sagittal plane, fetal image size, tissue harmonic imaging (THI), and speckle reduction filter (SRF) on the measurement of the nuchal translucency (NT) thickness using Volume NT software. MATERIALS AND METHODS: In 79 pregnant women, NT was measured using Volume NT. Firstly, the three-dimensional volumes were categorized based on the angle of deviation in 10 degrees intervals from the mid-sagittal plane. Secondly, the operator downsized the fetal image to less than 50% of the screen (Method A) and by magnifying the image (Method B). Next, the image was magnified until the fetal head and thorax occupied 75% of the screen, and the NT was measured (Method C). Lastly, NT values were acquired with THI and SRF functions on, with each function alternately on, and with both functions off. RESULTS: The mean differences in NT measurements were -0.09 mm (p<0.01) between two dimensional (2D) and a deviation of 31-40 degrees and -0.10 mm (p<0.01) between 2D and 41-50 degrees . The intraclass correlation coefficients (ICC) for 2D-NT and NT according to image size were 0.858, 0.923, and 0.928 for methods A, B, and C, respectively. The ICC for 2D-NT and NT with respect to the THI and SRF were 0.786, 0.761, 0.740, and 0.731 with both functions on, THI only, SRF only, and with both functions off, respectively. CONCLUSION: NT measurements made using Volume NT are affected by angle deviation from the mid-sagittal plane and fetal image size. Additionally, the highest correlation with 2D-NT was achieved when THI and SRF functions were used. PMID- 26256979 TI - Screening Ultrasound in Women with Negative Mammography: Outcome Analysis. AB - PURPOSE: To show the results of an audit of screening breast ultrasound (US) in women with negative mammography in a single institution and to analyze US detected cancers within a year and interval cancers. MATERIALS AND METHODS: During the year of 2006, 1974 women with negative mammography were screened with US in our screening center, and 1727 among them had pathologic results or any follow up breast examinations more than a year. We analyzed the distribution of Breast Imaging Reporting and Data System (BI-RADS) category and the performance outcome through follow up. RESULTS: Among 1727 women (age, 30-76 years, median 49.5 years), 1349 women (78.1%) showed dense breasts on mammography, 762 (44.1%) had previous breast US, and 25 women (1.4%) had a personal history of breast cancers. Test negatives were 94.2% (1.627/1727) [BI-RADS category 1 in 885 (51.2%), 2 in 742 (43.0%)]. The recall rate (=BI-RADS category 3, 4, 5) was 5.8%. Eight cancers were additionally detected with US (yield, 4.6 per 1000). The sensitivity, specificity, and positive predictive value (PPV1, PPV2) were 88.9%, 94.6%, 8.0%, and 28.0%, respectively. Eight of nine true positive cancers were stage I or in-situ cancers. One interval cancer was stage I cancer from BI-RADS category 2. CONCLUSION: Screening US detected 4.6 additional cancers among 1000. The recall rate was 5.8%, which is in lower bound of acceptable range of mammography (5-12%), according to American College of Radiology standard. PMID- 26256980 TI - Noninfectious Complications of Peritoneal Dialysis in Korean Children: A 26-Year Single-Center Study. AB - PURPOSE: The aim of this study was to investigate noninfectious complications of peritoneal dialysis (PD), including mechanical and metabolic complications, at a single center in Korea. MATERIALS AND METHODS: We analyzed data from 60 PD patients aged <=18 years (40 boys and 20 girls) during the period between 1986 and 2012. The collected data included gender, age, causes of PD, incidence of noninfectious complications, and treatment for the complications. RESULTS: The mean duration of PD therapy was 28.7+/-42.1 months (range 1-240 months). The most common cause of end-stage renal disease was glomerular disease (43.3%). There were no statistically significant differences between patients with and without mechanical complications regarding gender, age at the start of PD, and total duration of PD. Outflow failure was the most common catheter-related complication (14.3%), followed by leakage (10.0%) and hernia (8.6%). Metabolic complications, such as hyperglycemia and hypokalemia, were observed in three of 16 patients. The frequency of noninfectious complications of PD in our study was comparable with those in previous pediatric studies. PD was switched to hemodialysis (HD) in only three patients. CONCLUSION: Our results indicate that noninfectious complications of PD are common, though they hardly lead to catheter removal or HD in pediatric patients on PD. PMID- 26256981 TI - Changes of Heart Rate Variability during Methylphenidate Treatment in Attention Deficit Hyperactivity Disorder Children: A 12-Week Prospective Study. AB - PURPOSE: The aim of this study was to clarify the relationship between the autonomic nervous system and attention deficit hyperactivity disorder (ADHD) rating scales and to evaluate the usefulness of heart rate variability (HRV) as a psychophysiological biomarker for ADHD. MATERIALS AND METHODS: Subjects were recruited from outpatients in the Department of Child and Adolescent Psychiatry at the Korea University Medical Center from August 2007 to December 2010. Subjects received methylphenidate. Time- and frequency-domain analyses of HRV, the Korean ADHD rating scale (K-ARS), and computerized ADHD diagnostic system were evaluated before treatment. After a 12-week period of medication administration, we repeated the HRV measurements and K-ARS rating. RESULTS: Eighty-six subjects were initially enrolled and 37 participants completed the 12 week treatment and HRV measurements subsequent to the treatment. Significant correlations were found between the K-ARS inattention score and some HRV parameters. All of the HRV parameters, except the standard deviations of the normal-to-normal interval, very low frequency, and low frequency to high frequency, showed a significant positive correlation between baseline and endpoint measures in completers. High frequency (HF) and the square root of the mean squared differences of successive normal-to-normal intervals (RMSSD), which are related to parasympathetic vagal tone, showed significant decreases from baseline to endpoint. CONCLUSION: The HRV test was shown to be reproducible. The decrease in HF and RMSSD suggests that parasympathetic dominance in ADHD can be altered by methylphenidate treatment. It also shows the possibility that HRV parameters can be used as psychophysiological markers in the treatment of ADHD. PMID- 26256982 TI - Anastomotic Airway Complications after Lung Transplantation. AB - PURPOSE: Anastomotic airway complications are a major cause of morbidity and mortality after lung transplantation (LTx). In this study, the authors identified types and clinical outcomes of airway complications after LTx. MATERIALS AND METHODS: All bronchial anastomotic complications were analyzed in a total of 94 LTx cases involving 90 recipients who underwent surgery between July 2006 and May 2014. Fifteen LTx cases (14 recipients) with incomplete medical records for fiberoptic bronchoscopy (FBS) and three cases underwent heart-lung transplantation (HLT) were excluded. Postoperative FBS at 24-48 hours, 1, 3, 6, and 12 months, and then yearly after the transplantation were performed. RESULTS: A total of 76 LTx cases (75 recipients) were analyzed. The mean age of the recipients was 49.55 years (range, 18-71 years), and 38 (49.4%) were male. Twenty one out of 76 cases (27.6%) experienced early anastomotic complications, and 12 (15.8%) presented late anastomotic complications. The early anastomotic airway complications presented in various forms: stenosis, 1 case; narrowing, 1; necrosis & dehiscence, 3; fistula, 4; granulation, 10; and infection, 2. Late complications almost entirely presented in the form of bronchial stenosis; five recipients showed stenosis at the anastomosis site, and one of them showed improvement after ballooning. Five others were found to have stenosis at the bronchus intermedius, distal to the anastomosis site. Three of these patients showed improvement after ballooning or bronchoplasty. CONCLUSION: By serial surveillance via FBS after LTx, we detected anastomotic airway complications in 42.9% of cases, which were successfully managed with improved clinical outcomes. PMID- 26256983 TI - Efficacy of Direct Injection of Etanercept into Knee Joints for Pain in Moderate and Severe Knee Osteoarthritis. AB - PURPOSE: Osteoarthritic (OA) pain is largely considered to be inflammatory pain. However, during the last stage of knee OA, sensory nerve fibers in the knee are shown to be significantly damaged when the subchondral bone junction is destroyed, and this can induce neuropathic pain. Several authors have reported that tumor necrosis factor-alpha (TNFalpha) in a knee joint plays a crucial role in pain modulation. The purpose of the current study was to evaluate the efficacy of etanercept, a TNFalpha inhibitor, for pain in knee OA. MATERIALS AND METHODS: Thirty-nine patients with knee OA and a 2-4 Kellgren-Lawrence grading were evaluated in this prospective study. Patients were divided into two groups; hyaluronic acid (HA) and etanercept injection. All patients received a single injection into the knee. Pain scores were evaluated before and 4 weeks after injection using a visual analogue scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and they were compared between the groups. RESULTS: Before injection, VAS and WOMAC scores were not significantly different between the groups (p>0.05). Significant pain relief was found in the etanercept group at 1 and 2 weeks by VAS, and at 4 weeks by WOMAC score, compared with the HA group (p<0.05). No adverse events were observed in either group. CONCLUSION: Direct injection of etanercept into OA knee joints was an effective treatment for pain in moderate and severe OA patients. Furthermore, this finding suggests that TNFalpha is one factor that induces OA pain. PMID- 26256984 TI - Prevalence of Vitamin D Deficiency in Korean Children Presenting with Nonspecific Lower-Extremity Pain. AB - PURPOSE: Although interest in the role played by vitamin D in bone health is increasing, little is known about the role of this vitamin in musculoskeletal pain in children. This study aimed to assess the prevalence of vitamin D deficiency in children presenting with nonspecific lower extremity pains. MATERIALS AND METHODS: From 2011 to 2012, 183 children underwent evaluation for nonspecific lower-extremity pains. Patients with valid causes, such as fractures or transient synovitis, were excluded, as were those with underlying medical conditions, such as cerebral palsy and metabolic disease. Ultimately, 140 patients met the inclusion criteria. Levels of serum 25-hydroxy vitamin D [25 (OH)D], the ideal indicator of vitamin D status, were measured in these children. RESULTS: Eighty-seven boys (62.1%) and 53 girls (37.9%) were included. The mean age at presentation was 5.2 years (range, 2-15). Serum 25-(OH)D levels were <10 ng/mL in 5.7% of patients, 10 to <20 ng/mL in 51.4%, 20 to <30 ng/mL in 37.9%, and >=30 ng/mL in only 5.0%. Most patients visited the hospital in the winter (41.4%) (summer, 12.9%), and serum 25-(OH)D levels were also lowest in the winter (17.2+/-5.5 ng/mL). CONCLUSION: This study found a high prevalence of vitamin D deficiency or insufficiency in Korean children with nonspecific lower-extremity pains, indicating a positive association between vitamin D deficiency and growing pains. More attention should be directed toward vitamin D and its role in the optimization of bone health. PMID- 26256985 TI - Development of Thyroid-Associated Ophthalmopathy in Patients Who Underwent Total Thyroidectomy. AB - PURPOSE: To report clinical characteristics of thyroid-associated ophthalmopathy (TAO) in patients who previously underwent total thyroidectomy for thyroid cancer or a benign mass of the thyroid. MATERIALS AND METHODS: Of the patients who were diagnosed with TAO from March 2008 to March 2012, we performed a retrospective chart review on those who had undergone total thyroidectomy for thyroid cancer or a benign mass of the thyroid before the occurrence of ophthalmopathy. RESULTS: Of the 206 patients diagnosed with TAO, seven (3.4%) met the inclusion criteria. The mean age of the subjects was 47.4 years, and all were female. Six patients were diagnosed with papillary thyroid cancer, and one was diagnosed with a benign mass. The duration between total thyroidectomy and onset of TAO ranged from 3-120 months (median 48 months). Ophthalmic manifestations varied among cases. Except for the patient who was diagnosed with a benign mass, all patients showed hyperthyroid status and were under Synthroid hormone treatment at the time of TAO development. Five of these six patients had positive levels of thyroid stimulating hormone (TSH) receptor autoantibodies. CONCLUSION: TAO rarely develops after total thyroidectomy, and the mechanism of TAO occurrence is unclear. However, most patients showed abnormalities in thyroid function and TSH receptor autoantibodies. PMID- 26256986 TI - Analysis of Age-Related Changes in Asian Facial Skeletons Using 3D Vector Mathematics on Picture Archiving and Communication System Computed Tomography. AB - PURPOSE: There are marked differences in facial skeletal characteristics between Asian and Caucasian. However, ethnic differences in age-related facial skeletal changes have not yet been fully established. The aims of this study were to evaluate age-related changes in Asian midfacial skeletons and to explore ethnic differences in facial skeletal structures with aging between Caucasian and Asian. MATERIALS AND METHODS: The study included 108 men (aged 20-79 years) and 115 women (aged 20-81 years). Axial CT images with a gantry tilt angle of 0 were analyzed. We measured three-dimensional (3D) coordinates at each point with a pixel lens cursor in a picture archiving and communication system (PACS), and angles and widths between the points were calculated using 3D vector mathematics. We analyzed angular changes in 4 bony regions, including the glabellar, orbital, maxillary, and pyriform aperture regions, and changes in the orbital aperture width (distance from the posterior lacrimal crest to the frontozygomatic suture) and the pyriform width (between both upper margins of the pyriform aperture). RESULTS: All 4 midfacial angles in females and glabellar and maxillary angles in males showed statistically significant decreases with aging. On the other hand, the orbital and pyriform widths did not show statistically significant changes with aging. CONCLUSION: The results of this study suggest that Asian midfacial skeletons may change continuously throughout life, and that there may be significant differences in the midfacial skeleton between both sexes and between ethnic groups. PMID- 26256987 TI - Risk Assessment of Mortality Following Intraoperative Cardiac Arrest Using POSSUM and P-POSSUM in Adults Undergoing Non-Cardiac Surgery. AB - PURPOSE: The Physiological and Operative Severity Score for enUmeration of Mortality and morbidity (POSSUM) and its Portsmouth modification (P-POSSUM) are comprehensive assessment methods for evaluating patient and surgical factors widely used to predict 30-day mortality rates. In this retrospective study, we evaluated the usefulness of POSSUM and P-POSSUM in predicting 30-day mortality after intraoperative cardiac arrests in adult patients undergoing non-cardiac surgery. MATERIALS AND METHODS: Among 190486 patients who underwent anesthesia, 51 experienced intraoperative cardiac arrest as defined in our study protocol. Predicted mortality rates were calculated using POSSUM and P-POSSUM equations and were compared with actual outcomes using exponential and linear analyses. In addition, a receiver operating characteristic curve analysis was undertaken, and area-under-the-curve (AUC) values with confidence intervals (CIs) were calculated for POSSUM and P-POSSUM. RESULTS: Among the 51 patients with intraoperative cardiac arrest, 32 (62.7%) died within 30 days postoperatively. The overall predicted 30-day mortality rates using POSSUM and P-POSSUM were 65.5% and 57.5%, respectively. The observed-to-predicted (O:E) ratio for the POSSUM 30-day mortality was 1.07, with no significant difference between the observed and predicted values (chi2=4.794; p=0.779). P-POSSUM predicted mortality equally well, with an O:E ratio of 1.10 (chi2=8.905; p=0.350). AUC values (95% CI) were 0.771 (0.634-0.908) and 0.785 (0.651-0.918) for POSSUM and P-POSSUM, respectively. CONCLUSION: Both POSSUM and P-POSSUM performed well to predict overall 30-day mortality following intraoperative cardiac arrest in adults undergoing non-cardiac surgery at a university teaching hospital in Korea. PMID- 26256988 TI - Pharmacodynamic Estimate of Propofol-Induced Sedation and Airway Obstruction Effects in Obstructive Sleep Apnea-Hypopnea Syndrome. AB - PURPOSE: Sedatives must be carefully titrated for patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) as oversedation may lead to disastrous respiratory outcomes. This study aimed to investigate the relations between the effect-site concentration (Ce) of propofol and sedation and airway obstruction levels in patients with OSAHS. MATERIALS AND METHODS: In 25 patients with OSAHS, sedation was induced by 2% propofol using target-controlled infusion. Sedation and airway obstruction levels were assessed using the Observer's Assessment of Alertness/Sedation Scale and a four-category scale, respectively. The relationships between propofol Ce and sedation and airway obstruction were evaluated using a sigmoid Emax model. Pharmacodynamic modeling incorporating covariates was performed using the Nonlinear Mixed Effects Modeling VII software. RESULTS: Increased propofol Ce correlated with the depth of sedation and the severity of airway obstruction. Predicted Ce50(m) (Ce associated with 50% probability of an effect>=m) for sedation scores (m>=2, 3, 4, and 5) and airway obstruction scores (m>=2, 3, and 4) were 1.61, 1.78, 1.91, and 2.17 MUg/mL and 1.53, 1.64, and 2.09 MUg/mL, respectively. Including the apnea-hypopnea index (AHI) as a covariate in the analysis of Ce50(4) for airway obstruction significantly improved the performance of the basic model (p<0.05). CONCLUSION: The probability of each sedation and airway obstruction score was properly described using a sigmoid Emax model with a narrow therapeutic range of propofol Ce in OSAHS patients. Patients with high AHI values need close monitoring to ensure that airway patency is maintained during propofol sedation. PMID- 26256989 TI - Association of 5-HT3B Receptor Gene Polymorphisms with the Efficacy of Ondansetron for Postoperative Nausea and Vomiting. AB - PURPOSE: Postoperative nausea and vomiting (PONV) is a common problem after general anesthesia. Although 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists have significantly reduced PONV, over 35% of patients treated with ondansetron can experience PONV. In this study, we investigated whether the Y129S and -100_-102AAG deletion polymorphisms of the 5-HT3B receptor gene affect the efficacy of ondansetron in preventing PONV. MATERIALS AND METHODS: Two hundred and forty-five adult patients who underwent laparoscopic cholecystectomy were enrolled. Ondansetron 0.1 mg/kg was intravenously administered 30 minutes before the end of surgery. Genomic DNA was prepared from blood samples using a nucleic acid isolation device. Both the Y129S variant and the -100_-102AAG deletion variant were screened for using a single base primer extension assay and a DNA direct sequencing method, respectively. The relationship between genetic polymorphisms and clinical outcomes of ondansetron treatment was investigated. RESULTS: Among the 5-HT3B AAG deletion genotypes, the incidence of PONV was higher in patients with the homomutant than with other genotypes during the first 2 hours after surgery (p=0.02). There were no significant differences in the incidence of PONV among genotypes at 2-24 hours after surgery. In the Y129S variants of the 5-HT3B receptor gene, there were no significant differences in the incidence of PONV among genotypes during the first 2 hours and at 2-24 hours after surgery. CONCLUSION: The response to ondansetron for PONV was significantly influenced by the -100_-102AAG deletion polymorphisms of the 5-HT3B gene. Thus, the -100_-102AAG deletion variants may be a pharmacogenetic predictor for responsiveness to ondansetron for PONV. PMID- 26256990 TI - Effects of Alveolar Recruitment and Positive End-Expiratory Pressure on Oxygenation during One-Lung Ventilation in the Supine Position. AB - PURPOSE: Hypoxemia during one-lung ventilation (OLV) remains a serious problem, particularly in the supine position. We investigated the effects of alveolar recruitment (AR) and positive end-expiratory pressure (PEEP) on oxygenation during OLV in the supine position. MATERIALS AND METHODS: Ninety-nine patients were randomly allocated to one of the following three groups: a control group (ventilation with a tidal volume of 8 mL/kg), a PEEP group (the same ventilatory pattern with a PEEP of 8 cm H2O), or an AR group (an AR maneuver immediately before OLV followed by a PEEP of 8 cm H2O). The tidal volume was reduced to 6 mL/kg during OLV in all groups. Blood gas analyses, respiratory variables, and hemodynamic variables were recorded 15 min into TLV (TLV(baseline)), 15 and 30 min after OLV (OLV15 and OLV30), and 10 min after re-establishing TLV (TLV(end)). RESULTS: Ultimately, 92 patients were analyzed. In the AR group, the arterial oxygen tension was higher at TLV(end), and the physiologic dead space was lower at OLV15 and TLV(end) than in the control group. The mean airway pressure and dynamic lung compliance were higher in the PEEP and AR groups than in the control group at OLV15, OLV30, and TLV(end). No significant differences in hemodynamic variables were found among the three groups throughout the study period. CONCLUSION: Recruitment of both lungs with subsequent PEEP before OLV improved arterial oxygenation and ventilatory efficiency during video-assisted thoracic surgery requiring OLV in the supine position. PMID- 26256991 TI - The Long-Term Effect of an Independent Capacity Protocol on Emergency Department Length of Stay: A before and after Study. AB - PURPOSE: In this study, we determined the long-term effects of the Independent Capacity Protocol (ICP), in which the emergency department (ED) is temporarily used to stabilize patients, followed by transfer of patients to other facilities when necessary, on crowding metrics. MATERIALS AND METHODS: A before and after study design was used to determine the effects of the ICP on patient outcomes in an academic, urban, tertiary care hospital. The ICP was introduced on July 1, 2007 and the before period included patients presenting to the ED from January 1, 2005 to June 31, 2007. The after period began three months after implementing the ICP from October 1, 2007 to December 31, 2010. The main outcomes were the ED length of stay (LOS) and the total hospital LOS of admitted patients. The mean number of monthly ED visits and the rate of inter-facility transfers between emergency departments were also determined. A piecewise regression analysis, according to observation time intervals, was used to determine the effect of the ICP on the outcomes. RESULTS: During the study period the number of ED visits significantly increased. The intercept for overall ED LOS after intervention from the before-period decreased from 8.51 to 7.98 hours [difference 0.52, 95% confidence interval (CI): 0.04 to 1.01] (p=0.03), and the slope decreased from 0.0110 to -0.0179 hour/week (difference 0.0069, 95% CI: 0.0012 to 0.0125) (p=0.02). CONCLUSION: Implementation of the ICP was associated with a sustainable reduction in ED LOS and time to admission over a six-year period. PMID- 26256992 TI - Spontaneous Pneumomediastinum: A Rare Disease Associated with Chest Pain in Adolescents. AB - PURPOSE: Spontaneous pneumomediastinum (SPM) is a rare entity, with only a few cases reported, especially in adolescents. We aimed to analyze the clinical characteristics of SPM in adolescents and the diagnostic implications of computed tomography (CT) and esophagography therein. MATERIALS AND METHODS: This retrospective descriptive study was conducted as a review of medical records of 416 adolescents (10-18 years of age) with chest pain from March 2005 to June 2013. Information on clinical presentation, methods of diagnosis, hospital stay, and outcomes were collected and analyzed. RESULTS: Among adolescents complaining of chest pain, 11 patients had SPM (11/416, 2.64%). All patients presented with pleuritic chest pain, and 54.5% reported neck pain as the most common associated complaint. Clinical findings were nonspecific, and initial chest X-ray assessment was diagnostic only in three of 11 patients. However, reassessment of chest X-ray revealed diagnostic findings of SPM in five of the remaining eight patients. CT was diagnostic in all patients, while esophagography and echocardiogram were uninformative. Symptomatic improvement was noted within 2.45+/-1.2 hours (range, 0.5 to 4) after supportive care; mean hospital stay was 4.54+/-0.99 days (range, 2 to 6). No recurrence was observed. CONCLUSION: SPM is a rare disease that should be considered in adolescent patients with pleuritic chest pain. Careful reading of initial chest X-rays is important to avoiding further unnecessary investigations. SPM is self-limited and treatment is supportive; nevertheless, if there are no indications of esophageal rupture, urgent esophagography is not recommended. PMID- 26256993 TI - Snakebite in Korea: A Guideline to Primary Surgical Management. AB - PURPOSE: Snakebite is an emergency which causes local symptoms such as pain and edema around the bite. Systemic symptoms may also develop, such as dizziness or renal failure, and may even cause death. The purpose of this research was to assess the validity and safety of snakebite protocol for surgery when treating snakebite patients. MATERIALS AND METHODS: Retrospective research was performed on patients who were admitted after being treated at the emergency center from January 2008 to December 2012. When necessary, debridement was also performed, and 46 of 111 patients (41.4%) underwent debridement. Those who had received debridement without antivenom administration due to a positive skin reaction test were classified as group A, and group B received antivenom and delayed debridement. We reviewed the emergency and admission charts of the patients in each group and recorded and compared their age, sex, bite site, severity of local and general symptoms, time to receive antivenin, and complications. RESULTS: Of the ten patients (21.7%) in group A, two (66.6%) developed cellulites, and one of them experienced skin necrosis, resulting in a skin graft. In group B, there were 36 patients (78.2%), 19 (52.7%) of whom developed cellulitis. Skin necrosis occurred in two patients, and one of these patients received a skin graft. Compartment syndrome was found in one patient, and fasciotomy and a skin graft were performed. CONCLUSION: The treatment protocol implemented to treat snakebite patients admitted to the emergency center during this research was safely and properly followed during surgical treatment. PMID- 26256994 TI - High-Dose Vitamin C Promotes Regression of Multiple Pulmonary Metastases Originating from Hepatocellular Carcinoma. AB - We report a case of regression of multiple pulmonary metastases, which originated from hepatocellular carcinoma after treatment with intravenous administration of high-dose vitamin C. A 74-year-old woman presented to the clinic for her cancer related symptoms such as general weakness and anorexia. After undergoing initial transarterial chemoembolization (TACE), local recurrence with multiple pulmonary metastases was found. She refused further conventional therapy, including sorafenib tosylate (Nexavar). She did receive high doses of vitamin C (70 g), which were administered into a peripheral vein twice a week for 10 months, and multiple pulmonary metastases were observed to have completely regressed. She then underwent subsequent TACE, resulting in remission of her primary hepatocellular carcinoma. PMID- 26256995 TI - Invasive Primary Colonic Aspergillosis in the Immunocompetent Host without Classical Risk Factors. AB - Invasive aspergillosis (IA), generally considered an opportunistic infection in immunocompromised hosts, is associated with high morbidity and mortality. IA commonly occurs in the respiratory tract with isolated reports of aspergillosis infection in the nasal sinuses, central nervous system, skin, liver, and urinary tract. Extra-pulmonary aspergillosis is usually observed in disseminated disease. To date, there are a few studies regarding primary and disseminated gastrointestinal (GI) aspergillosis in immunocompromised hosts. Only a few cases of primary GI aspergillosis in non-immunocompromised hosts have been reported; of these, almost all of them involved the upper GI tract. We describe a very rare case of IA involving the lower GI tract in the patient without classical risk factors that presented as multiple colon perforations and was successfully treated by surgery and antifungal treatment. We also review related literature and discuss the characteristics and risk factors of IA in the immunocompetent hosts without classical risk factors. This case that shows IA should be considered in critically ill patients, and that primary lower GI aspergillosis may also occur in the immunocompetent hosts without classical risk factors. PMID- 26256996 TI - The Preventive Effect of Belongings in Penetrating Trauma. PMID- 26256997 TI - A rare complication: an attempt of retrieval of an aortic valve wrapped with pig tail catheter during transcatheter aortic valve implantation. AB - Transcatheter aortic valve implantation is preferred to treat high surgical risk patients with severe aort stenosis. Wrapping of a pig tail catheter with device struts during transcatheter aortic valve implantation is a very rare complication. In this report, we present the images and videos of an attempt of retrieval of an aortic valve wrapped with pig tail catheter during transcatheter aortic valve implantation in a 71-year-old man. PMID- 26256998 TI - Tendon development and diseases. AB - Tendon is a uniaxial connective tissue component of the musculoskeletal system. Tendon is involved in force transmission between muscle and bone. Tendon injury is very common and debilitating but tendon repair remains a clinical challenge for orthopedic medicine. In vertebrates, tendon is mainly composed of type I collagen fibrils, displaying a parallel organization along the tendon axis. The tendon-specific spatial organization of type I collagen provides the mechanical properties for tendon function. In contrast to other components of the musculoskeletal system, tendon biology is poorly understood. An important goal in tendon biology is to understand the mechanisms involved in the production and assembly of type I collagen fibrils during development, postnatal formation, and healing processes in order to design new therapies for tendon repair. In this review we highlight the current understanding of the molecular and mechanical signals known to be involved in tenogenesis during development, and how development provides insights into tendon healing processes. WIREs Dev Biol 2016, 5:5-23. doi: 10.1002/wdev.201 For further resources related to this article, please visit the WIREs website. PMID- 26256999 TI - Elevated serum ghrelin, tumor necrosis factor-alpha and interleukin-6 in congenital heart disease. AB - BACKGROUND: The aim of this study was to investigate the association of congenital heart disease (CHD) with serum ghrelin, tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6. METHOD: Sixty-three children with CHD, hospitalized between January 2012 and September 2014 at Wuhan Women and Children's Health Care Center, were selected as the study group. Additionally, 28 healthy individuals who had physical examinations at this hospital were selected as the control group. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum ghrelin, TNF-alpha and IL-6. SPSS 18.0 and Comprehensive Meta analysis 2.0 were used for data analysis. RESULTS: There was significant difference in weight, height and body mass index (BMI; all P < 0.05) but not in age or sex (both P > 0.05) between the cyanotic CHD (CCHD), acyanotic CHD (ACHD) and control groups. On one-way analysis of variance serum ghrelin, TNF-alpha and IL-6 in both the CCHD and ACHD groups had a tendency to be higher compared with the control group (all P < 0.05), whereas, on Pearson correlation analysis, there was a correlation between serum ghrelin and BMI (all P < 0.05), and TNF-alpha was negatively, and IL-6 positively, correlated with BMI (all P < 0.05). Meta analysis further demonstrated that serum ghrelin, TNF-alpha and IL-6 in both the CCHD and ACHD groups were higher than in the control group (all P < 0.05). CONCLUSION: Serum ghrelin, TNF-alpha and IL-6 are elevated in children with CHD, and may play a role in the development and progression of CHD. PMID- 26257000 TI - A cultural setting where the other-race effect on face recognition has no social motivational component and derives entirely from lifetime perceptual experience. AB - Competing approaches to the other-race effect (ORE) see its primary cause as either a lack of motivation to individuate social outgroup members, or a lack of perceptual experience with other-race faces. Here, we argue that the evidence supporting the social-motivational approach derives from a particular cultural setting: a high socio-economic status group (typically US Whites) looking at the faces of a lower status group (US Blacks) with whom observers typically have at least moderate perceptual experience. In contrast, we test motivation-to individuate instructions across five studies covering an extremely wide range of perceptual experience, in a cultural setting of more equal socio-economic status, namely Asian and Caucasian participants (N = 480) tested on Asian and Caucasian faces. We find no social-motivational component at all to the ORE, specifically: no reduction in the ORE with motivation instructions, including for novel images of the faces, and at all experience levels; no increase in correlation between own- and other-race face recognition, implying no increase in shared processes; and greater (not the predicted less) effort applied to distinguishing other-race faces than own-race faces under normal ("no instructions") conditions. Instead, the ORE was predicted by level of contact with the other-race. Our results reject both pure social-motivational theories and also the recent Categorization Individuation model of Hugenberg, Young, Bernstein, and Sacco (2010). We propose a new dual-route approach to the ORE, in which there are two causes of the ORE lack of motivation, and lack of experience--that contribute differently across varying world locations and cultural settings. PMID- 26257002 TI - Mitotic transformation of TRAMM/TrappC12. PMID- 26257001 TI - Response to energy depletion: miR-451/AMPK loop. PMID- 26257003 TI - Trithorax group genes in hematopoiesis. PMID- 26257004 TI - Cell therapy--showing cells the way home. PMID- 26257005 TI - Regulation of the polo kinase during cytokinesis. PMID- 26257006 TI - Repressing the repressor: Fra1 controls plasma cell generation. PMID- 26257007 TI - WISp39 and Hsp90: actin' together in cell migration. PMID- 26257008 TI - Dynamic and steady state 1-D model of mediated electron transfer in a porous enzymatic electrode. AB - A 1-D mathematical model of a porous enzymatic electrode exhibiting the mediated electron transfer (MET) mechanism has been developed. As a model system, glucose oxidation catalyzed by immobilized glucose oxidase (GOx) in the presence of a co immobilized tetrathiafulvalene (TTF) mediator in the porous electrode matrix has been selected. The balance equations for potential fields in the electron- and ion-conducting phases as well as concentration field have been formulated, solved numerically and validated experimentally under steady state conditions. The relevant kinetic parameters of the lumped reaction kinetics have been obtained by global optimization. The confidence intervals (CIs) of each parameter have been extracted from the respective likelihood. The parameter study has shown that the parameters related to mediator consumption/regeneration steps can be responsible for the shift of the reaction onset potential. Additionally, the model has shown that diffusion of the oxidized mediator out of the catalyst layer (CL) plays a significant role only at more positive potentials and low glucose concentrations. Only concentration profiles in different layers influence the electrode performance while other state fields like potential distributions in different phases have no impact on the performance. The concentration profiles reveal that all electrodes work through; the observed limiting currents are diffusion reaction limiting. The normalized electrode activity decreases with an increase of enzyme loading. According to the model, the reason for this observation is glucose depletion along the CL at higher enzyme loadings. Comparison with experiments advices a decrease of enzyme utilization at higher enzyme loadings. PMID- 26257009 TI - Calcium and Sudden Cardiac Death in End-Stage Renal Disease. AB - Sudden cardiac death (SCD) accounts for a quarter of all deaths in end-stage renal disease (ESRD) patients. While causative mechanisms of SCD in this high risk population remain poorly defined, interaction of the vulnerable myocardium with dialysis-related arrhythmic triggers is thought to play a major role. Recent evidence suggests that dialysis-induced derangement of calcium concentrations contributes to the increased risk of all-cause and cardiovascular mortality, vascular calcification, and SCD. Current KDIGO guidelines recommend avoiding high dialysate calcium concentrations as a precaution against adverse outcomes of increased calcium burden and vascular calcification. Conversely, low calcium concentration is also implicated in the development of SCD via increased QT dispersion and prolonged QT interval. Consequently, the optimal dialysate calcium concentration in dialysis patients remains debated and further studies are needed to establish the best strategy for managing calcium in dialysis patients. PMID- 26257010 TI - Monte Carlo method based QSAR modeling of maleimide derivatives as glycogen synthase kinase-3beta inhibitors. AB - The Monte Carlo method was used for QSAR modeling of maleimide derivatives as glycogen synthase kinase-3beta inhibitors. The first QSAR model was developed for a series of 74 3-anilino-4-arylmaleimide derivatives. The second QSAR model was developed for a series of 177 maleimide derivatives. QSAR models were calculated with the representation of the molecular structure by the simplified molecular input-line entry system. Two splits have been examined: one split into the training and test set for the first QSAR model, and one split into the training, test and validation set for the second. The statistical quality of the developed model is very good. The calculated model for 3-anilino-4-arylmaleimide derivatives had following statistical parameters: r(2)=0.8617 for the training set; r(2)=0.8659, and r(m)(2)=0.7361 for the test set. The calculated model for maleimide derivatives had following statistical parameters: r(2)=0.9435, for the training, r(2)=0.9262 and r(m)(2)=0.8199 for the test and r(2)=0.8418, r(av)(m)(2)=0.7469 and ?r(m)(2)=0.1476 for the validation set. Structural indicators considered as molecular fragments responsible for the increase and decrease in the inhibition activity have been defined. The computer-aided design of new potential glycogen synthase kinase-3beta inhibitors has been presented by using defined structural alerts. PMID- 26257011 TI - Antimicrobial peptide lysozyme has the potential to promote mouse hair follicle growth in vitro. AB - Lysozyme is a well-known antimicrobial peptide that exists widely in mammalian skin and it is also expressed by pilosebaceous units. However, the exact location of lysozyme in hair follicles and whether it exerts any direct effects on hair follicle growth are unclear. To determine whether lysozyme affected hair growth in vitro, micro-dissected mouse vibrissae follicles (VFs) were treated in serum free organ culture for 3 days with lysozyme (1-10MUg/ml). After that, the effects of lysozyme on dermal papilla (DP) cells were also investigated. Lysozyme was mainly identified in DP and dermal sheath regions of VF by immunochemistry. In addition, 5-10MUg/ml lysozyme had a promoting effect on shaft production. It was also associated with significant proliferation of matrix keratinocytes by immunofluorescence observation. Furthermore, lysozyme promoted hair growth by increasing the levels of alkaline phosphatase and lymphoid enhancer factor 1 in DP, as determined by Western blotting. These results indicate that lysozyme is a promoter of VF growth via enhancing the hair-inductive capacity of DP cells during organ culture. PMID- 26257012 TI - Thermodynamic stability of high phosphorus concentration in silicon nanostructures. AB - Doping of Si nanocrystals (NCs) has been the subject of a strong experimental and theoretical debate for more than a decade. A major difficulty in the understanding of dopant incorporation at the nanoscale is related to the fact that theoretical calculations usually refer to thermodynamic equilibrium conditions, whereas, from the experimental point of view, impurity incorporation is commonly performed during NC formation. This latter circumstance makes impossible to experimentally decouple equilibrium properties from kinetic effects. In this report, we approach the problem by introducing the dopants into the Si NCs, from a spatially separated dopant source. We induce a P diffusion flux to interact with the already-formed and stable Si NCs embedded in SiO2, maintaining the system very close to the thermodynamic equilibrium. Combining advanced material synthesis, multi-technique experimental quantification and simulations of diffusion profiles with a rate-equation model, we demonstrate that a high P concentration (above the P solid solubility in bulk Si) within Si NCs embedded in a SiO2 matrix corresponds to an equilibrium property of the system. Trapping within the Si NCs embedded in a SiO2 matrix is essentially diffusion limited with no additional energy barrier, whereas de-trapping is prevented by a binding energy of 0.9 eV, in excellent agreement with recent theoretical findings that highlighted the impact of different surface terminations (H- or O-terminated NCs) on the stability of the incorporated P atoms. PMID- 26257013 TI - Amine Chemistry Method for Selective Enrichment of N-Linked Glycopeptides for Glycoproteomics Analysis. AB - An amine chemistry method was developed for the extraction of N-glycopeptides using amine-functionalized beads for glycoproteomics analysis. Two reductive amination reactions between primary amine and aldehyde were employed in this approach. The first one was to block the primary amines in the peptides by addition of formaldehyde and sodium cyanoborohydride into the peptide sample, and the second one was to couple the glycopeptides onto solid phase beads by incubating the glycopeptides containing aldehyde groups (oxidized by periodate) with the amine-functionalized beads in the presence of sodium cyanoborohydride. It was demonstrated that the blocking of primary amines in the peptides by the first reductive amination reaction prior to the periodate oxidation made the amine chemistry method very efficient and sensitive. This new method was validated by analysis of glycoprotein standards as well as proteome samples. It was found that this new method led to significant increase in the identification of N-glycosites compared with the conventional hydrazide chemistry method. PMID- 26257014 TI - Kounis syndrome with Samter-Beer triad treated with intracoronary adrenaline. AB - Kounis syndrome is a well-described clinical condition characterized by the simultaneous occurrence of chest pain and an allergic reaction accompanied by clinical and laboratory findings of angina caused by inflammatory mediators released during an allergic insult. We present the case of a 50-year-old male with the Samter-Beer triad of asthma, nasal polyps, and salicylate intolerance with an ST elevation myocardial infarction complicated with cardiac arrest due to multi-vessel coronary artery spasm secondary to aspirin anaphylaxis. Adrenaline is recommended during anaphylaxis but is controversial in Kounis syndrome as it may worsen coronary spasm. We report the use of intracoronary adrenaline in successfully reversing coronary artery spasm in this hemodynamically unstable patient. PMID- 26257015 TI - Spontaneous middle cranial fossa cerebrospinal fluid otorrhea in adults. AB - OBJECTIVES/HYPOTHESIS: The goals of this study are to: 1) investigate the urgency for repair of middle cranial fossa spontaneous cerebrospinal fluid (CSF) leaks in adults, and 2) review the literature and treatment recommendations for adult spontaneous CSF otorrhea. DATA SOURCES: 1) All patients who were referred to a tertiary center with spontaneous CSF otorrhea, exposed middle cranial fossa dura, or encephalocele from 2004 to 2015; and 2) landmark references on spontaneous CSF leaks REVIEW METHODS: Electronic medical records of patients with a documented spontaneous CSF leak, exposed dura, or encephalocele were reviewed. Subjects were excluded if they had a congenital, traumatic, or iatrogenic CSF leak. Main outcome measure was duration of CSF leak and development of meningitis after clinical presentation. RESULTS: Twenty-two patients (27 ears) who were at risk for meningitis from spontaneous CSF otorrhea, encephalocele, or a dural breach with or without mastoiditis were evaluated. Duration of CSF leaks in patients who refused repair or who continued to have CSF leak after repair or prior to successful repair ranged from 4 months to 11 years. Duration of encephaloceles and dural exposure in an uninfected mastoid ranged from 24 months to 6 years. Only one patient presented with meningitis. None of these 22 patients developed meningitis during the time periods they were under our care. CONCLUSION: Should patients with CSF otorrhea, exposed dura, or encephalocele refuse operation, it may be reasonable to follow them with close observation and education about warning signs for meningitis. PMID- 26257017 TI - Coaxial CoMoO4 nanowire arrays with chemically integrated conductive coating for high-performance flexible all-solid-state asymmetric supercapacitors. AB - Flexible all-solid-state supercapacitors have offered promising applications as novel energy storage devices based on their merits, such as small size, low cost, light weight and high wearability for high-performance portable electronics. However, one major challenge to make flexible all-solid-state supercapacitors depends on the improvement of electrode materials with higher electrical conductivity properties and longer cycling stability. In this article, we put forward a simple strategy to in situ synthesize 1D CoMoO4 nanowires (NWs), using highly conductive CC and an electrically conductive PPy wrapping layer on CoMoO4 NW arrays for high performance electrode materials. The results show that the CoMoO4/PPy hybrid NW electrode exhibits a high areal specific capacitance of ca. 1.34 F cm(-2) at a current density of 2 mA cm(-2), which is remarkably better than the corresponding values for a pure CoMoO4 NW electrode of 0.7 F cm(-2). An excellent cycling performance of nanocomposites of up to 95.2% (ca. 1.12 F cm( 2)) is achieved after 2000 cycles compared to pristine CoMoO4 NWs. In addition, we fabricate flexible all-solid-state ASC which can be cycled reversibly in the voltage range of 0-1.7 V, and exhibits a maximum energy density of 104.7 W h kg( 1) (3.522 mW h cm(-3)), demonstrating great potential for practical applications in flexible energy storage electronics. PMID- 26257016 TI - Sialylation of neurites inhibits complement-mediated macrophage removal in a human macrophage-neuron Co-Culture System. AB - The complement system has been implicated in the removal of dysfunctional synapses and neurites during development and in disease processes in the mouse, but it is unclear how far the mouse data can be transferred to humans. Here, we co-cultured macrophages derived from human THP1 monocytes and neurons derived from human induced pluripotent stem cells, to study the role of the complement system in a human model. Components of the complement system were expressed by the human macrophages and human neuronal culture, while receptors of the complement cascade were expressed by human macrophages as shown via gene transcript analysis and flow cytometry. We mimicked pathological conditions leading to an altered glycocalyx by treatment of human neurons with sialidases. Desialylated human neurites were opsonized by the complement component C1q. Furthermore, human neurites with an intact sialic acid cap remained untouched, while desialylated human neurites were removed and ingested by human macrophages. While blockage of the complement receptor 1 (CD35) had no effect, blockage of CD11b as part of the complement receptor 3 (CR3) reversed the effect on macrophage phagocytosis of desialylated human neurites. Data demonstrate that in the human system sialylation of the neuronal glycocalyx serves as an inhibitory flag for complement binding and CR3-mediated phagocytosis by macrophages. PMID- 26257018 TI - Cell wall protection by the Candida albicans class I chitin synthases. AB - Candida albicans has four chitin synthases from three different enzyme classes which deposit chitin in the cell wall, including at the polarized tips of growing buds and hyphae, and sites of septation. The two class I enzymes, Chs2 and Chs8, are responsible for most of the measurable chitin synthase activity in vitro, but their precise biological functions in vivo remain obscure. In this work, detailed phenotypic analyses of a chs2Deltachs8Delta mutant have shown that C. albicans class I chitin synthases promote cell integrity during early polarized growth in yeast and hyphal cells. This was supported by live cell imaging of YFP-tagged versions of the class I chitin synthases which revealed that Chs2-YFP was localized at sites of polarized growth. Furthermore, a unique and dynamic pattern of localization of the class I enzymes at septa of yeast and hyphae was revealed. Phosphorylation of Chs2 on the serine at position 222 was shown to regulate the amount of Chs2 that is localized to sites of polarized growth and septation. Independently from this post-translational modification, specific cell wall stresses were also shown to regulate the amount of Chs2 that localizes to specific sites in cells, and this was linked to the ability of the class I enzymes to reinforce cell wall integrity during early polarized growth in the presence of these stresses. PMID- 26257019 TI - Solution to Statistical Challenges in Proteomics Is More Statistics, Not Less. AB - In any high-throughput scientific study, it is often essential to estimate the percent of findings that are actually incorrect. This percentage is called the false discovery rate (abbreviated "FDR"), and it is an invariant (albeit, often unknown) quantity for any well-formed study. In proteomics, it has become common practice to incorrectly conflate the protein FDR (the percent of identified proteins that are actually absent) with protein-level target-decoy, a particular method for estimating the protein-level FDR. In this manner, the challenges of one approach have been used as the basis for an argument that the field should abstain from protein-level FDR analysis altogether or even the suggestion that the very notion of a protein FDR is flawed. As we demonstrate in simple but accurate simulations, not only is the protein-level FDR an invariant concept, when analyzing large data sets, the failure to properly acknowledge it or to correct for multiple testing can result in large, unrecognized errors, whereby thousands of absent proteins (and, potentially every protein in the FASTA database being considered) can be incorrectly identified. PMID- 26257020 TI - Double-dose hepatitis B vaccination in people with HIV. PMID- 26257023 TI - Retrograde pedal access with a 20-gauge intravenous cannula after failed antegrade recanalization of a tibialis anterior artery in a diabetic patient: a case report. AB - Retrograde tibiopedal approach is being used frequently in below-the-knee vascular interventions. In patients with diabetic foot pathology, complex anatomy often requires a retrograde technique when the distal vascular anatomy and puncture site is suitable. The dorsalis pedis and posterior tibial arteries can be punctured because of their relatively superficial position. We report a retrograde puncturing technique in patients with chronic total occlusions. After failed antegrade recanalization, puncturing and cannulation of a tiny dorsalis pedis artery with a narrow bore [20-gauge (0.8 mm)] intravenous cannula is described. PMID- 26257022 TI - Effects of MAO inhibition and a combination of minor alkaloids, beta-carbolines, and acetaldehyde on nicotine self-administration in adult male rats. AB - INTRODUCTION: Although nicotine is the primary reinforcing constituent in cigarettes, there is evidence that other constituents in cigarette smoke may interact with nicotine to reinforce smoking behavior. METHODS: The present experiments investigated whether a novel combination of these cigarette smoke constituents would increase nicotine self-administration in adult male rats. The constituents included five minor alkaloids (anabasine, nornicotine, cotinine, myosmine, and anatabine), two beta-carbolines (harman and norharman), and acetaldehyde. All doses were indexed to be proportional to concentrations in cigarette smoke given a standard dose of nicotine used in rodent self administration, or ten times higher than this standard. To model MAO inhibition seen in chronic smokers, some groups received separate injections of tranylcypromine prior to each self-administration session. RESULTS: Tranylcypromine increased low-dose nicotine self-administration independent of other smoke constituents, which had no effect on self-administration behavior. The effect of tranylcypromine was confirmed across a large range of reinforcement schedules. The effect of tranylcypromine on low-dose nicotine self-administration was observed regardless of whether the injection was delivered 1-h or 23-h prior to the self-administration session, consistent with the interpretation that MAO inhibition was responsible for the increase in self-administration, instead of acute off-target effects. CONCLUSIONS: These data suggest that this cocktail of constituents does not significantly alter the primary reinforcing effects of nicotine, but constituents that inhibit MAO may increase the primary reinforcing effects of nicotine, especially at low doses. PMID- 26257021 TI - Safety and immunogenicity of double-dose versus standard-dose hepatitis B revaccination in non-responding adults with HIV-1 (ANRS HB04 B-BOOST): a multicentre, open-label, randomised controlled trial. AB - BACKGROUND: Revaccination with double-dose hepatitis B vaccine has been recommended in HIV-infected patients who do not respond to standard vaccination, but has not yet been assessed. We aimed to compare the safety and immunogenicity of a reinforced hepatitis B revaccination protocol with the standard revaccination schedule in HIV-infected patients not responding to primary vaccination. METHODS: We did this multicentre, open-label, randomised controlled trial, at 53 centres in France. HIV-infected adults (aged >=18 years), with CD4 counts of 200 cells per MUL or more and no response to a previous hepatitis B vaccination or a 20 MUg booster dose, were randomly assigned (1:1), according to a computer-generated randomisation list with permuted blocks (block sizes of two to six), to receive either standard-dose (20 MUg) or double-dose (40 MUg) recombinant hepatitis B vaccine at weeks 0, 4, and 24. Randomisation was stratified by baseline CD4 count (200-349 vs >=350 cells per MUL). Patients and treating physicians were not masked to treatment allocation, but the randomisation list was concealed from the investigators who assigned participants to the vaccination groups. The primary endpoint was the proportion of responders, defined as patients with hepatitis B surface antibody (anti-HBs) titres of 10 mIU/mL or more, at week 28. We did analysis by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT00670839. FINDINGS: Between May 19, 2008, and May 8, 2011, 178 participants were randomly assigned to the standard-dose group (n=90) or the double-dose group (n=88), of whom 176 (98%) participants were included in the primary efficacy analysis. At week 28, we recorded a response in 60 patients (67%, 95% CI 57-77) in the standard-dose group versus 64 patients (74%, 63-82) in the double-dose group (p=0.334). Except for more frequent local reactions in the double-dose group than the standard-dose group (13 [15%] vs four [4%] patients; p=0.020), there was no difference in safety between groups. INTERPRETATION: In adults with HIV-1 who have not responded to previous hepatitis B vaccination, double-dose revaccination did not achieve a higher response rate than did revaccination with standard single-dose regimen. However, the safety profile was similar between treatment groups. Our results should be assessed in future studies before double-dose vaccine can be considered for the standard of care of vaccine non-responders. FUNDING: French National Institute for Medical Research-French National Agency for Research on AIDS and Viral Hepatitis. PMID- 26257026 TI - Enhanced photovoltaic performances of graphene/Si solar cells by insertion of a MoS2 thin film. AB - Transition-metal dichalcogenides exhibit great potential as active materials in optoelectronic devices because of their characteristic band structure. Here, we demonstrated that the photovoltaic performances of graphene/Si Schottky junction solar cells were significantly improved by inserting a chemical vapor deposition (CVD)-grown, large MoS2 thin-film layer. This layer functions as an effective electron-blocking/hole-transporting layer. We also demonstrated that the photovoltaic properties are enhanced with the increasing number of graphene layers and the decreasing thickness of the MoS2 layer. A high photovoltaic conversion efficiency of 11.1% was achieved with the optimized trilayer graphene/MoS2/n-Si solar cell. PMID- 26257025 TI - T-type calcium channels contribute to calcium disturbances in brain during hyponatremia. AB - Disturbance of calcium homeostasis is implicated in the normal process of aging and brain pathology prevalent in the elderly such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. Previous studies demonstrated that applying a hyponatremic iso-osmotic (low-NaCl) artificial cerebrospinal fluid (ACSF) to rodent hippocampus causes extracellular calcium to rapidly decrease. Restoring normonatremia after low-NaCl treatment causes a rapid increase in extracellular calcium that overshoots baseline. This study examined the amplitude, timing, and mechanism of these surprising calcium changes. We also tested whether hyponatremia increased calcium entry into brain cells or calcium binding to chondroitin sulfate (CS), a negatively charged constituent of the extracellular matrix (ECM) that may be occupied by sodium during normonatremia. We report three major findings. First we show that CS does not contribute to extracellular calcium changes during low-NaCl treatments. Second, we show that the time to minimum extracellular calcium during low-NaCl treatment is significantly shorter than the time to maximum extracellular calcium in recovery from low-NaCl treatment. Third, we show that the decrease in extracellular calcium observed during hyponatremia is attenuated by ML 218, a highly selective T-type calcium channel blocker. Together these data suggest that calcium rapidly enters cells at the onset of low-NaCl treatment and is extruded from cells when normonatremia is restored. Calcium binding to CS does not significantly contribute to calcium changes in brain during hyponatremia. Differences in timing suggest that extracellular calcium changes during and in recovery from hyponatremia occur by distinct mechanisms or by a multistep process. Finally, partial block of extracellular calcium influx by ML 218 suggests that T-type channels are involved in calcium entering cells during hyponatremia. Given the high prevalence of hyponatremia among elderly patients and the growing understanding of calcium's role in multiple neurologic pathologies, this study promotes a novel approach for studying and potentially preventing the effects of hyponatremia on calcium dysregulation in brain tissue. PMID- 26257027 TI - Prospective study on the incidence of bladder/cloacal exstrophy and epispadias in Europe. AB - OBJECTIVE: On behalf of the European Society of Paediatric Urology (ESPU), a prospective study was designed with the aim of defining the actual number of babies born with bladder exstrophy, cloacal exstrophy, and epispadias in Europe over a 12-month period, and verifying the distribution of the exstrophy patients born during the study period among the different paediatric urology centres in Europe. STUDY DESIGN: The study was structured with a chief investigator and one national investigator for each country enrolled in the study. The national investigators nominated one local investigator for each European centre of paediatric surgery/paediatric urology and urology where the exstrophy complex could potentially be treated. The local investigators were responsible for reporting babies treated in their institutions for bladder/cloacal exstrophy and/or epispadias. During 2010, every 3 months, an electronic survey (Figure) was e-mailed to the local investigators asking them to report babies treated or referred for treatment during the previous 3 months. RESULTS: One-hundred and sixteen centres in 27 European counties were enrolled in the study. The overall response rate for the four online surveys was 79%. Two-hundred and thirty-eight babies were reported to be born with a condition within the bladder exstrophy epispadias complex (BEEC): 71 primary epispadias (66 males), 146 classic bladder exstrophy (97 males) of which two were female bladder exstrophy variant, and 21 cloacal exstrophy (17 males). Two of 67 (3%) male epispadias, 24/146 (16.4%) bladder exstrophy, and 6/21 (28%) cloacal exstrophy were antenatally diagnosed. Associated anomalies were reported in 2/71 (2.8%) epispadias patients, 8/146 (5.5%) bladder exstrophy patients, and 15/21 (71.4%) cloacal exstrophy patients. One-hundred and forty-seven (62%) of the 238 babies born in Europe with a condition within the exstrophy spectrum during 2010 were transferred from other institutions for treatment (36 male epispadias, 97 bladder exstrophy, and 14 cloacal exstrophy). Only 12 centres treated six or more exstrophy and or epispadias patients during the study period; 52 treated between one and five patients, of which 22 treated only one case in 12 months. DISCUSSION: This study provides a contemporary incidence of the BEEC in Europe. It demonstrates also that only a minority (19%) of the European centres involved in the treatment of exstrophy can be considered "high volume" exstrophy centres. CONCLUSION: There is a case for proposing a rationalisation of the treatment of this group of conditions in a small number of exstrophy units around Europe. PMID- 26257028 TI - Management strategies for idiopathic urethritis. AB - INTRODUCTION: Williams and Mikhael (1971) described idiopathic urethritis (IU) as a self-limiting condition that affects boys aged 5-15 years, with symptoms of urethrorrhagia, dysuria and haematuria. However, a proportion of boys will remain symptomatic for several years, and may develop urethral stricture (Poch et al., 2007; Palagiri et al., 2003). There is no universally effective treatment for IU, although various strategies have been employed. OBJECTIVE: To review the presentation and long-term outcomes of boys with IU, and present the efficacy of management strategies that have been utilised. STUDY DESIGN: A retrospective review was performed of all boys with IU. It was based on clinical and cystoscopic findings for presentation, medical history, management and clinical progress. RESULTS: Fifty-four boys were included, with a median age of 11 years (range 5-15 years) at presentation. The median duration of symptoms was 18 months (range 2-132 months). The median follow-up was 18.5 months (range 1-120 months). Seven (13.0%) boys had early urethral stricture at initial cystourethroscopy, and one (1.9%) developed stricture during follow-up. Thirty-six boys (66.7%) had previous circumcision and four (7.4%) had meatal stenosis. Eight (14.8%) had previous hypospadias repair. CONCLUSION: Whilst 50% of boys with IU do not require any specific treatment, those with severe/unremitting symptoms may benefit from a trial of urethral steroids or short-term urethral catheterisation. The mechanisms of benefit from these modalities are unclear and they require further evaluation. PMID- 26257029 TI - A bibliometric analysis of global Zika research. PMID- 26257030 TI - Amebic liver abscess; the role of PCR in the absence of a serologic reaction. PMID- 26257024 TI - Studying polyglutamine diseases in Drosophila. AB - Polyglutamine (polyQ) diseases are a family of dominantly transmitted neurodegenerative disorders caused by an abnormal expansion of CAG trinucleotide repeats in the protein-coding regions of the respective disease-causing genes. Despite their simple genetic basis, the etiology of these diseases is far from clear. Over the past two decades, Drosophila has proven to be successful in modeling this family of neurodegenerative disorders, including the faithful recapitulation of pathological features such as polyQ length-dependent formation of protein aggregates and progressive neuronal degeneration. Additionally, it has been valuable in probing the pathogenic mechanisms, in identifying and evaluating disease modifiers, and in helping elucidate the normal functions of disease causing genes. Knowledge learned from this simple invertebrate organism has had a large impact on our understanding of these devastating brain diseases. PMID- 26257031 TI - Levels of selected urinary metabolites of volatile organic compounds among children aged 6-11 years. AB - Data from National Health and Nutrition Examination Survey for the years 2011 2012 were used to evaluate variability in the observed levels of 20 urinary metabolites of volatile organic compounds (VOCs) by age, gender, and race/ethnicity among children aged 6-11 years. Exposure to environmental tobacco smoke was positively associated with the levels of selected metabolites of acrylonitrile, 1,3-butadiene, cyanide, and propylene oxide in a dose-response manner. Levels of the selected metabolites of acrolein, acrylonitrile, 1,3 butadiene, styrene, toluene, and xylene decreased with increase in age. Levels of 1-bromopropane decreased with number of rooms in the house but the reverse was true for 1,3-butadiene, carbon-disulfide, and N,N-dimethylformamide. Levels of most of the 20 metabolites did not vary with gender. Non-Hispanic white children had higher adjusted levels of N-Acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHBMA), N-Acetyl-S-(N-methylcarbamoyl)-L-cysteine (AMCC), and phenylglyoxylic acid (PGA) than non-Hispanic black children. Non-Hispanic white children had statistically significantly higher adjusted levels of N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L cysteine (GAMA), trans, trans-Muconic acid (MU), and N-Acetyl-S-(N methylcarbamoyl)-L-cysteine (AMCC) than non-Hispanic Asian children but statistically significantly lower levels of N-Acetyl-S-(n-propyl)-L-cysteine (BPMA) than non-Hispanic Asian children. Non-Hispanic Asian children had the lowest levels of 13 of the 20 metabolites among four major racial/ethnic groups but highest levels for three metabolites. For selected metabolites of acrolein, acrylamide, acrylonitrile-vinyl chloride-ethylene oxide, benzene, 1,3-butadien, crotonaldehyde, cyanide, ethylbenzene-styrene, and toluene, children had statistically significantly higher levels than nonsmoking adults. These results demonstrate how vulnerable children are to being exposed to harmful chemicals like VOCs in their own homes. PMID- 26257034 TI - An overview of peptide and peptoid foldamers in medicinal chemistry. AB - INTRODUCTION: Foldamers are artificial self-organizing systems with various critical properties: i) a stable and designable secondary structure; ii) a larger molecular surface as compared with ordinary organic drug molecules; iii) appropriate control of the orientation of the side-chain functional groups; iv) resistance against proteolytic degradation, which leads to potentially increased oral bioavailability and a longer serum half-life relative to ordinary alpha peptides; and v) the lower conformational freedom may result in increased receptor binding in comparison with the natural analogs. Areas covered: This article covers the general properties and types of foldamers. This includes highlighted examples of medicinal chemical applications, including antibacterial and cargo molecules, anti-Alzheimer compounds and protein-protein interaction modifiers. Expert opinion: Various new foldamers have been created with a range of structures and biological applications. Membrane-acting antibacterial foldamers have been introduced. A general property of these structures is their amphiphilic nature. The amphiphilicity can be stationary or induced by the membrane binding. Cell-penetrating foldamers have been described which serve as cargo molecules, and foldamers have been used as autophagy inducers. Anti Alzheimer compounds too have been created and the greatest breakthrough was attained via the modification of protein-protein interactions. This can serve as the chemical and pharmaceutical basis for the relevance of foldamers in the future. PMID- 26257032 TI - Transfer of perfluoroalkyl substances from mother to fetus in a Spanish birth cohort. AB - INTRODUCTION: Prenatal exposure to perfluoroalkyl substances (PFAS) might affect child health; thus estimating PFAS fetal burden is relevant. PFAS fetal burden is best estimated in cord samples; previous studies have used either maternal plasma or serum during pregnancy as proxy, but their validity is not clear. We aimed to evaluate PFAS transfer between mother and fetus and determine its predictors in a Spanish birth cohort. METHODS: We measured perfluorobutane sulfonate (PFBS), perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorononanoate (PFNA) in maternal blood and cord serum from 66 mother-child pairs. We used Spearman's rank coefficients to correlate PFAS concentrations in first trimester maternal plasma and serum, with cord serum samples. We assessed PFAS placental transfer by calculating maternal to cord ratios and examined their association with maternal socio-demographic characteristics and child sex using linear regression models. RESULTS: Median concentrations of PFAS (ng/mL) of PFHxS, PFOS, PFOA, and PFNA in maternal plasma (0.79, 6.18, 2.85 and 0.84, respectively) and serum (0.84, 6.99, 2.97 and 0.85) were higher than in cord serum (0.40, 1.86, 1.90 and 0.32). PFBS was not detected. Positive Spearman's correlations (p-values<0.001) were found between maternal plasma and serum (?>=0.80), maternal plasma and cord (?>=0.66), and maternal serum and cord samples (?>=0.67). Maternal plasma to cord ratios were above 1 (PFHxS: 2.35 [95%CI: 2.05, 2.70], PFOS: 3.33 [3.05, 3.62], PFOA: 1.37 [1.27, 1.48], PFNA: 2.39 [2.18, 2.63]); maternal serum to cord ratios were similar. Maternal to cord ratios decreased with maternal age, but not with other socio-demographic factors. CONCLUSIONS: Our results suggest that PFAS fetal body burden can be assessed using as proxy maternal plasma or serum collected early in pregnancy. Maternal age might influence PFAS placental transfer. PMID- 26257033 TI - Room Temperature Multiferroicity of Charge Transfer Crystals. AB - Room temperature multiferroics has been a frontier research field by manipulating spin-driven ferroelectricity or charge-order-driven magnetism. Charge-transfer crystals based on electron donor and acceptor assembly, exhibiting simultaneous spin ordering, are drawing significant interests for the development of all organic magnetoelectric multiferroics. Here, we report that a remarkable anisotropic magnetization and room temperature multiferroicity can be achieved through assembly of thiophene donor and fullerene acceptor. The crystal motif directs the dimensional and compositional control of charge-transfer networks that could switch magnetization under external stimuli, thereby opening up an attractive class of all-organic nanoferronics. PMID- 26257035 TI - Cardiovascular risk profiles of adults with type-2 diabetes treated at urban hospitals in Riyadh, Saudi Arabia. AB - Diabetes mellitus substantially increases cardiovascular disease (CVD) risk. Among Saudi Arabian citizens with diabetes, little is known about the prevalence and control of other CVD risk factors. We extracted data from medical records of a random selection of 422 patients seen between 2008 and 2012 at two diabetic clinics in Riyadh, Saudi Arabia. We calculated the proportion of patients who had additional CVD risk factors: obesity (body mass index ? 30 kg/m(2)), hypertension (BP ? 140/90 mmHg), elevated cholesterol fractions, and multiple risk factors). Further, we calculated the proportion of patients meeting the American Diabetes Association's recommended care targets for each risk factor. Of 422 patients (mean age, 52 years), half were women, 56% were obese, 45% had hypertension, and 77% had elevated LDL concentrations. In addition to diabetes, 70% had two or more CVD risk factors. Although 9% met both target HbA1c and BP values, only 3.5% had optimum HbA1c, BP, and lipid values. In Saudi Arabia's best diabetes clinics, most patients have poor control of their disease. This huge disease burden and related care gaps have important health and financial implications for the country. PMID- 26257037 TI - Editorial: Bioengineering for a better quality of life. PMID- 26257038 TI - Process analytical technologies in food industry - challenges and benefits: A status report and recommendations. PMID- 26257040 TI - Application of Good's buffers to pH imaging using hyperpolarized (13)C MRI. AB - N-(2-Acetamido)-2-aminoethanesulfonic acid (ACES), one of Good's buffers, was applied to pH imaging using hyperpolarized (13)C magnetic resonance spectroscopy. Rapid NMR- and MRI-based pH measurements were obtained by exploiting the sensitive pH-dependence of its (13)C chemical shift within the physiologic range. PMID- 26257041 TI - Upper airway stimulation for obstructive sleep apnea: The surgical learning curve. AB - OBJECTIVES/HYPOTHESIS: To determine the effect of surgeon experience with an upper airway stimulation (UAS) system on surgical time and complication rates. STUDY DESIGN: Retrospective review. METHODS: Surgical procedure times and complication rates observed in patients implanted at 22 study centers as part of a phase III, multicenter surgical trial of upper airway nerve stimulation therapy for obstructive sleep apnea were reviewed. RESULTS: The study included 126 subjects who were predominantly male (83%), with a mean age of 54.5 years (range = 31-80 years), and the mean body mass index was 28.4 +/- 2.6. There were an average of 5.7 (range = 1-22) surgical implants per site, with an average surgical time of 2.52 +/- 0.98 hours (range = 1.08-6.0 hours). The surgical implant time decreased significantly with surgeon experience, from 2.98 +/- 1.18 hours for a surgeon's first implant (n = 22) to 2.08 +/- 0.55 hours for the fifth implant (n = 10, P = .025). Surgical time was inversely correlated with the site implant number (rho = -0.334, P < .001). Procedure-specific complications were uncommon and self-limited and did not decrease appreciably with increasing experience. CONCLUSIONS: Surgical time for implantation of the UAS system decreased significantly after the first five implants and then stabilized. The rate of surgical complications did not decrease with surgeon experience, although this may be attributable to the low overall rate of serious surgical complications and low number of implants at some centers. LEVEL OF EVIDENCE: 4. PMID- 26257042 TI - Effect of Selected Volatiles on Two Stored Pests: The Fungus Fusarium verticillioides and the Maize Weevil Sithophilus zeamais. AB - New agronomic practices and technology enabled Argentina a larger production of cereal grains, reaching a harvest yield of 26.5 million metric tons of maize, of which, about 40% was exported. However, much of the maize production is lost annually by the attack of fungi and insects (2.6 million tons). In this study, the antifungal effect of selected volatiles on Fusarium verticillioides, its mycotoxin production, and the repellent and insecticidal activities against the weevill Sithophilus zeamais, an insect vector of F. verticillioides, were evaluated. The compounds tested were (2E)-2-hexenal, (2E)-2-nonenal, (2E,6Z)-2,6 nonadienal, 1-pentanol, 1-hexanol, 1-butanol, 3-methyl-1-butanol, pentanal, 2 decanone, and 3-decanone, which occur in the blend of volatile compounds emitted by various cereal grains. The most active antifungals were the aldehydes (2E)-2 nonenal, (2E)-2-hexenal, and (2E,6Z)-2,6-nonadienal (minimum inhibitory concentration values of <0.03, 0.06, and 0.06 mM, respectively). The occurrence of fumonisin B1 also was prevented because these compounds completely inhibited fungal growth. The best insecticidal fumigant activities against the maize weevil were shown by 2-decanone and 3-decanone (lethal concentration <= 54.6 MUL/L (<0.28 mM)). Although, all tested compounds showed repellent activity against S. zeamais at a concentration of 4 MUL/L, (2E,6Z)-2,6-nonadienal was the most active repellent compound. These results demonstrate the potential of (2E,6Z)-2,6 nonadienal to be used as a natural alternative to synthetic pesticides on F. verticillioides and S. zeamais. PMID- 26257043 TI - Conflict and cooperation over sex: the consequences of social and genetic polyandry for reproductive success in dunnocks. AB - Conflict and cooperation within and between the sexes are among the driving forces that lead to the evolution of mating systems. Among mating strategies, female genetic polyandry and male reproductive cooperation pose challenging evolutionary questions regarding the maintenance of systems where one sex suffers from reduced fitness. Here, we investigate the consequences of social and genetic polyandry for reproductive success of females and males in a population of the dunnock, Prunella modularis. We show that female multiple mating ameliorates the negative effects of inbreeding. We, however, found little evidence that females engage in extra-group (pair) mating with less related or more heterozygous males. Breeding in socially polyandrous groups reduced the amount of paternity lost to extra-group males, such that, on average, cobreeding and monogamous males fledged a similar number of young. Importantly, c. 30% of cobreeding male dyads were related, suggesting they could gain indirect fitness benefits. Taken together, cobreeding males achieve equivalent reproductive success to monogamous counterparts under most circumstances. Our study has revealed unexpected complexities in the variable mating system of dunnocks in New Zealand. Our results differ from the well-known Cambridge dunnock study and can help our understanding of the evolution and maintenance of various breeding systems in the animal kingdom. PMID- 26257044 TI - Intralesional hyaluronic acid: an innovative treatment for Peyronie's disease. AB - OBJECTIVE: The significantly different effects of several conservative treatments for Peyronie's disease (PD) led us to conduct this study to evaluate the effectiveness of local treatment with injectable hyaluronic acid (HA) for patients with this disease. MATERIALS AND METHODS: The study included 83 PD patients who underwent treatment and 81 PD patients who did not (control group). The inclusion criteria were: penile plaque volume <1 cm(3); clinical characteristics and ultrasonographic appearance compatible with active inflammation; and penile curvature <45 degrees . The medical history of all PD patients was collected. Patients undertook six tests: routine laboratory tests; penile auto-photography during erection; dynamic penile colour-duplex ultrasound study; penile X-ray (mammography technique); index of erectile function questionnaire (IIEF); and pain intensity questionnaire (visual analog scale). Treated patients received thirty penile infiltrations by injection of 20 mg HA in 6 months. Follow-up checks were conducted at the end of treatment and 12 and 24 months after treatment. RESULTS: At 12-month follow-up all treated PD patients had experienced three statistically significant outcomes: reduction in plaque size (-93.7 %, p < 0.0001); improvement in penile curvature (-9.01 degrees , p < 0.0001); and improvement in penile rigidity (mean IIEF score +3.8) with an average increase of 21.1 % (p < 0.0001). Furthermore, the improvements remained substantially stable at 24-month follow-up. CONCLUSION: Considering the minimally invasive approach in this study, the absence of major side effects, and the significant treatment outcomes achieved, we conclude that intralesional penile injections with HA are effective for treating Peyronie's disease. PMID- 26257045 TI - Prognostic Factors for Outcome in Localized Extremity Rhabdomyosarcoma. Pooled Analysis from Four International Cooperative Groups. AB - BACKGROUND: Extremity rhabdomyosarcomas do not always show satisfactory outcomes. We analyzed data from 643 patients treated in 14 studies conducted by European and North American groups between 1983 and 2004 to identify factors predictive of outcome. PROCEDURE: Clinical factors, including age; histology; site of primary (hand and foot vs. other); size; invasiveness (T stage); nodal involvement (N stage); and treatment factors, including post-surgical group; chemotherapy type and duration; radiotherapy; and treatment (before or after 1995); were evaluated for impact on overall survival (OS). RESULTS: 5-year OS were 67% (se 1.8). Multivariate analysis showed that lower OS correlated with age >3 years, T2 and N1 stage, incomplete initial surgery, treatment before 1995, and European cooperative group treatment. Patients with gross residual disease after initial incomplete resection/biopsy had similar outcomes in both continental groups. The better global survival of patients treated in American studies was accounted for by differences in outcome in the subset of those with grossly resected tumors (OS 86% [se 3] for COG patients vs. 68% [se 4] for European patients (P = 0.004)). When excluding chemotherapy duration from the model, analysis in this subset of patients showed that cooperative group (P = 0.001), site (P = 0.001), and T stage (P = 0.05) were all significant. However, after adding duration of chemotherapy (>=27 weeks) to the model, only primary site remained significant (P = 0.006). CONCLUSION: This meta-analysis confirms the role of many established prognostic factors but identifies for the first time that chemotherapy duration may have an impact on outcome in patients with grossly resected tumors. PMID- 26257046 TI - Vital need to engage the community in HIV control in South Africa. AB - According to the latest 2014 UNAIDS report, which was based on the 2012 South African National HIV Prevalence, Incidence & Behavior Survey, there were between 6.3 and 6.4 million HIV infected people in South Africa. Although the number of new infections appears to have declined in the past 5 years, 370,000 new infections were still estimated to occur in 2013. Young, black women were most at risk with a very high incidence of 4.5%. Of the infected, only 2.2 million were on antiretroviral therapy (ART), meaning that the majority living with HIV was not virally suppressed and thus at risk of infecting somebody else. Eight out of 10 South Africans still believed they were at low risk of HIV infection. Condom use was declining and multiple sexual partnerships were increasing. These findings raise questions about whether current control efforts are properly addressing the drivers of the epidemic. Recent behavior change campaigns target intergenerational sex and blame the high transmission rates among girls on 'sugar daddies' thus diverting attention away from common risk behaviors in the general population. Reduction of new infections is crucial. Much of the current global HIV debate focuses on treatment as prevention (TasP) - an approach hampered by resource problems and the fact that most people are infected by someone who is unaware of his/her HIV status. This raises doubts TasP alone is a sufficient and sustainable solution to prevention. It is not enough to mainly treat those already infected; there is also a need to allocate more resources to address the root causes - ART plus norm and behavior change. We thus propose increased attention to common sexual and social norms and behaviors. New and harmful community norms are one of the major drivers of the ongoing spread of HIV among young women and men in black communities. Addressing sexual risk behaviors and the gender and sexual norms that influence them to scale requires ensuring communities are provided with skills to reflect on the individual and social mechanisms by which these risk behaviors are generated and normalized. To achieve this, partnerships must be formed between political leaders, researchers, technocrats and affected communities. Considering the severity of the epidemic and the continued high incidence of HIV, it is high time to review the current strategy to HIV control in South Africa and allocate more resources to approaches that emphasize community driven norm and behavior change. PMID- 26257047 TI - Haitian and international responders' and decision-makers' perspectives regarding disability and the response to the 2010 Haiti earthquake. AB - BACKGROUND: Following disasters, persons with disabilities (PWD) are especially vulnerable to harm, yet they have commonly been excluded from disaster planning, and their needs have been poorly addressed during disaster relief. Following the 2010 Haiti earthquake, thousands of individuals experienced acute injuries. Many more individuals with preexisting disabilities experienced heightened vulnerability related to considerations including safety, access to services, and meeting basic needs. OBJECTIVE: The objective of this research was to better understand the perceptions of responders and decision-makers regarding disability and efforts to address the needs of PWD following the 2010 earthquake. DESIGN: We conducted a qualitative study using interpretive description methodology and semistructured interviews with 14 Haitian and 10 international participants who were involved in the earthquake response. RESULTS: Participants identified PWD as being among the most vulnerable individuals following the earthquake. Though some forms of disability received considerable attention in aid efforts, the needs of other PWD did not. Several factors were identified as challenges for efforts to address the needs of PWD including lack of coordination and information sharing, the involvement of multiple aid sectors, perceptions that this should be the responsibility of specialized organizations, and the need to prioritize limited resources. Participants also reported shifts in local social views related to disability following the earthquake. CONCLUSIONS: Addressing the needs of PWD following a disaster is a crucial population health challenge and raises questions related to equity and responsibility for non-governmental organizations, governments, and local communities. PMID- 26257048 TI - Measuring population health: costs of alternative survey approaches in the Nouna Health and Demographic Surveillance System in rural Burkina Faso. AB - BACKGROUND: There are more than 40 Health and Demographic Surveillance System (HDSS) sites in 19 different countries. The running costs of HDSS sites are high. The financing of HDSS activities is of major importance, and adding external health surveys to the HDSS is challenging. To investigate the ways of improving data quality and collection efficiency in the Nouna HDSS in Burkina Faso, the stand-alone data collection activities of the HDSS and the Household Morbidity Survey (HMS) were integrated, and the paper-based questionnaires were consolidated into a single tablet-based questionnaire, the Comprehensive Disease Assessment (CDA). OBJECTIVE: The aims of this study are to estimate and compare the implementation costs of the two different survey approaches for measuring population health. DESIGN: All financial costs of stand-alone (HDSS and HMS) and integrated (CDA) surveys were estimated from the perspective of the implementing agency. Fixed and variable costs of survey implementation and key cost drivers were identified. The costs per household visit were calculated for both survey approaches. RESULTS: While fixed costs of survey implementation were similar for the two survey approaches, there were considerable variations in variable costs, resulting in an estimated annual cost saving of about US$45,000 under the integrated survey approach. This was primarily because the costs of data management for the tablet-based CDA survey were considerably lower than for the paper-based stand-alone surveys. The cost per household visit from the integrated survey approach was US$21 compared with US$25 from the stand-alone surveys for collecting the same amount of information from 10,000 HDSS households. CONCLUSIONS: The CDA tablet-based survey method appears to be feasible and efficient for collecting health and demographic data in the Nouna HDSS in rural Burkina Faso. The possibility of using the tablet-based data collection platform to improve the quality of population health data requires further exploration. PMID- 26257049 TI - Cell surface localised Hsp70 is a cancer specific regulator of clathrin independent endocytosis. AB - The stress inducible heat shock protein 70 (Hsp70) is present specifically on the tumour cell surface yet without a pro-tumour function revealed. We show here that cell surface localised Hsp70 (sHsp70) supports clathrin-independent endocytosis (CIE) in melanoma models. Remarkably, ability of Hsp70 to cluster on lipid rafts in vitro correlated with larger nano-domain sizes of sHsp70 in high sHsp70 expressing cell membranes. Interfering with Hsp70 oligomerisation impaired sHsp70 mediated facilitation of endocytosis. Altogether our findings suggest that a sub fraction of sHsp70 co-localising with lipid rafts enhances CIE through oligomerisation and clustering. Targeting or utilising this tumour specific mechanism may represent an additional benefit for anti-cancer therapy. PMID- 26257050 TI - Ammonium oxalate-extractable uronic acids positively affect biomass enzymatic digestibility by reducing lignocellulose crystallinity in Miscanthus. AB - Based on systems biology analyses of total 179 representative Miscanthus accessions, ammonium oxalate (AO)-extractable uronic acids could either positively affect biomass digestibility or negatively alter lignocellulose crystallinity at p<0.01 or 0.05. Comparative analysis of four typical pairs of Miscanthus samples indicated that the AO-extractable uronic acids, other than hexoses and pentoses, play a predominant role in biomass enzymatic saccharification upon various chemical pretreatments, consistent with observations of strong cell tissue destruction in situ and rough biomass residue surface in vitro in the unique Msa24 sample rich in uronic acids. Notably, AO extraction of uronic acids could significantly increase lignocellulose CrI at p<0.05, indicating that uronic acids-rich polymers may have the interactions with beta-1,4-glucan chains that reduce cellulose crystallinity. It has also suggested that increasing of uronic acids should be a useful approach for enhancing biomass enzymatic digestibility in Miscanthus and beyond. PMID- 26257051 TI - Effect of multi-stage inoculation on the bacterial and fungal community structure during organic municipal solid wastes composting. AB - In this study, PCR-DGGE method was applied to investigate the impact of multi stage inoculation treatment on the community composition of bacterial and fungal during municipal solid wastes (MSW) composting process. The results showed that the high temperature period was extended by the multi-stage inoculation treatment, 1day longer than initial-stage inoculation treatment, and 5days longer than non-inoculation treatment. The temperature of the secondary fermentation increased to 51 degrees C with multi-stage inoculation treatment. The multi-stage inoculation method improved the community diversity of bacteria and fungi that the diversity indexes reached the maximum on the 17days and 20days respectively, avoided the competition between inoculations and indigenous microbes, and enhanced the growth of dominant microorganisms. The DNA sequence indicated that various kinds of uncultured microorganisms with determined ratios were detected, which were dominant microbes during the whole fermentation process. These findings call for further researches of compost microbial cultivation technology. PMID- 26257052 TI - Lower-extremity ulcers: diagnosis and management. AB - Chronic wounds of the lower extremities are occurring with increasing prevalence. They affect millions of individuals annually, representing both a significant health risk and a large economic burden. Chronic wounds are associated with increased mortality and substantial morbidity due to infection, pain, limitation of daily activities, and psychosocial consequences. To manage these wounds effectively, clinicians must be able to diagnose and manage their aetiology. Diagnosis starts with determining whether the wound is one of the four most common chronic wounds: venous leg ulcers, diabetic foot ulcers, pressure ulcers and arterial ulcers. Moreover, despite many recent advances in wound care, the challenge of managing chronic wounds is complicated by the lack of consistently accepted diagnostic methods and wound-care standards. We present a comprehensive yet condensed approach to managing lower-extremity ulcers, from diagnosis to basic management. PMID- 26257053 TI - Parietal and Frontal Cortex Encode Stimulus-Specific Mnemonic Representations during Visual Working Memory. AB - Working memory (WM) enables the storage and manipulation of information in an active state. WM storage has long been associated with sustained increases in activation across a network of frontal and parietal cortical regions. However, recent evidence suggests that these regions primarily encode information related to general task goals rather than feature-selective representations of specific memoranda. These goal-related representations are thought to provide top-down feedback that coordinates the representation of fine-grained details in early sensory areas. Here, we test this model using fMRI-based reconstructions of remembered visual details from region-level activation patterns. We could reconstruct high-fidelity representations of a remembered orientation based on activation patterns in occipital visual cortex and in several sub-regions of frontal and parietal cortex, independent of sustained increases in mean activation. These results challenge models of WM that postulate disjoint frontoparietal "top-down control" and posterior sensory "feature storage" networks. PMID- 26257054 TI - Analysis of chromium and sulphate origins in construction recycled materials based on leaching test results. AB - Twenty samples of recycled aggregates from construction and demolition waste (CDW) with different compositions collected at six recycling plants in the Andalusia region (south of Spain) were characterised according to the Landfill Directive criteria. Chromium and sulphate were identified as the most critical compounds in the leachates. To detect the sources of these two pollutant constituents in recycled aggregate, environmental assessments were performed on eight construction materials (five unused ceramic materials, two old crushed concretes and one new mortar manufactured in the laboratory). The results confirmed that leached sulphate and Cr were mainly released by the ceramic materials (bricks and tiles). To predict the toxicological consequences, the oxidation states of Cr (III) and Cr (VI) were measured in the leachates of recycled aggregates and ceramic materials classified as non-hazardous. The bricks and tiles mainly released total Cr as Cr (III). However, the recycled aggregates classified as non-hazardous according to the Landfill Directive criteria mainly released Cr (VI), which is highly leachable and extremely toxic. The obtained results highlight the need for legislation that distinguishes the oxidative state in which chromium is released into the environment. Leaching level regulations must not be based solely on total Cr, which can lead to inaccurate predictions. PMID- 26257055 TI - Complete nitrification-denitrification of swine manure in a full-scale, non conventional composting system. AB - A full-scale composting plant (track type, aerated by screws), treating liquid swine manure (94.8% on mass basis) with straw (<0.8%) and sawdust (4.4%), was monitored. The main objectives were testing the performance of the process and assessing its environmental sustainability. Particular attention was dedicated to verify the possibility that this process could determine significant mass reduction, along with Nitrogen reduction, mainly by denitrification. Emissions were evaluated by measuring NH3, N2O and CH4 (by static chamber), H2S and odor emissions (by dynamic olfactometry). Quality and quantity of inputs and outputs and process parameters (redox, oxygen, and temperature) were monitored. The process produced a mature, highly humified (Humification Index=0.27), solid product with 92.8% mass reduction (mainly evaporation), and nitrogen reduction (85.8% referred to input TN). The process was revealed to be environmentally sustainable: emissions of odors and H2S resulted negligible; emissions of N-N2O represented 0.18% of TN input, while emissions of N-NH3 represented 0.87% of input TN. Microbiological analyses determined the presence of 10(7) CFU/g of bacteria related to N cycle and real time PCR demonstrated the presence in the final product of 4.77 ? 10(7) couples of genes of Bacterial amoA/gTS and 2.46 ? 10(7) couples NosZ/gTS, indicating nitrification and complete denitrification. These results exhibit that nitrification and complete denitrification can efficiently occur in a composting process effectively transforming N2O into N2 as consequence of the optimized alternation of aerated and anoxic phases in the feedstock. PMID- 26257056 TI - Life Cycle Assessment of Mixed Municipal Solid Waste: Multi-input versus multi output perspective. AB - This paper analyses four strategies for managing the Mixed Municipal Solid Waste (MMSW) in terms of their environmental impacts and potential advantages by means of Life Cycle Assessment (LCA) methodology. To this aim, both a multi-input and a multi-output approach are applied to evaluate the effect of these perspectives on selected impact categories. The analyzed management options include direct landfilling with energy recovery (S-1), Mechanical-Biological Treatment (MBT) followed by Waste-to-Energy (WtE) conversion (S-2), a combination of an innovative MBT/MARSS (Material Advanced Recovery Sustainable Systems) process and landfill disposal (S-3), and finally a combination of the MBT/MARSS process with WtE conversion (S-4). The MARSS technology, developed within an European LIFE PLUS framework and currently implemented at pilot plant scale, is an innovative MBT plant having the main goal to yield a Renewable Refined Biomass Fuel (RRBF) to be used for combined heat and power production (CHP) under the regulations enforced for biomass-based plants instead of Waste-to-Energy systems, for increased environmental performance. The four scenarios are characterized by different resource investment for plant and infrastructure construction and different quantities of matter, heat and electricity recovery and recycling. Results, calculated per unit mass of waste treated and per unit exergy delivered, under both multi-input and multi-output LCA perspectives, point out improved performance for scenarios characterized by increased matter and energy recovery. Although none of the investigated scenarios is capable to provide the best performance in all the analyzed impact categories, the scenario S-4 shows the best LCA results in the human toxicity and freshwater eutrophication categories, i.e. the ones with highest impacts in all waste management processes. PMID- 26257057 TI - Wnt addiction of genetically defined cancers reversed by PORCN inhibition. AB - Enhanced sensitivity to Wnts is an emerging hallmark of a subset of cancers, defined in part by mutations regulating the abundance of their receptors. Whether these mutations identify a clinical opportunity is an important question. Inhibition of Wnt secretion by blocking an essential post-translational modification, palmitoleation, provides a useful therapeutic intervention. We developed a novel potent, orally available PORCN inhibitor, ETC-1922159 (henceforth called ETC-159) that blocks the secretion and activity of all Wnts. ETC-159 is remarkably effective in treating RSPO-translocation bearing colorectal cancer (CRC) patient-derived xenografts. This is the first example of effective targeted therapy for this subset of CRC. Consistent with a central role of Wnt signaling in regulation of gene expression, inhibition of PORCN in RSPO3 translocated cancers causes a marked remodeling of the transcriptome, with loss of cell cycle, stem cell and proliferation genes, and an increase in differentiation markers. Inhibition of Wnt signaling by PORCN inhibition holds promise as differentiation therapy in genetically defined human cancers. PMID- 26257059 TI - NKX6.1 functions as a metastatic suppressor through epigenetic regulation of the epithelial-mesenchymal transition. AB - The transcription factor NKX6.1 (NK6 homeobox 1) is important in the development of pancreatic beta-cells and neurons. Although recent publications show that NKX6.1 is hypermethylated and downregulated during tumorigenesis, the function of NKX6.1 in carcinogenesis remains elusive. Here, we address the metastasis suppressor function of human NKX6.1 using cell, animal and clinical analyses. Our data show that NKX6.1 represses tumor formation and metastatic ability both in vitro and in vivo. Mechanistically, NKX6.1 suppresses cell invasion by inhibiting the epithelial-to-mesenchymal transition (EMT). NKX6.1 directly enhances the mRNA level of E-cadherin by recruiting BAF155 coactivator and represses that of vimentin and N-cadherin by recruiting RBBP7 (retinoblastoma binding protein 7) corepressor. Clinical cancer tumors with metastasis show low NKX6.1 protein expression coinciding with low E-cadherin and high vimentin expression. Our results demonstrate that NKX6.1 functions as an EMT suppressor by interacting with different epigenetic modifiers, making it a potential novel therapeutic option. PMID- 26257058 TI - Effects of p21-activated kinase 1 inhibition on 11q13-amplified ovarian cancer cells. AB - p21-activated kinases (Paks) are Cdc42/Rac-activated serine-threonine protein kinases that regulate several key cancer-relevant signaling pathways, such as the Mek/Erk, PI3K/Akt and Wnt/b-catenin signaling pathways. Pak1 is frequently overexpressed and/or hyperactivated in different human cancers, including human breast, ovary, prostate and brain cancer, due to amplification of the PAK1 gene in an 11q13 amplicon. Genetic or pharmacological inactivation of Pak1 has been shown to reduce proliferation of different cancer cells in vitro and reduce tumor progression in vivo. In this work, we examined the roles of Pak1 in cellular and animal models of PAK1-amplified ovarian cancer. We found that inhibition of Pak1 leads to decreased proliferation and migration in PAK1-amplified/overexpressed ovarian cancer cells, and has no effect in cell that lack such amplification/overexpression. Further, we observed that loss of Pak1 function causes 11q13-amplified ovarian cancer cells to arrest in the G2/M phase of the cell cycle. This arrest correlates with activation of p53 and p21(Cip) and decreased expression of cyclin B1. These findings suggest that small-molecule inhibitors of Pak1 may have a therapeutic role in the ~25% of ovarian cancers characterized by PAK1 gene amplification. PMID- 26257060 TI - GNAS(R201H) and Kras(G12D) cooperate to promote murine pancreatic tumorigenesis recapitulating human intraductal papillary mucinous neoplasm. AB - Intraductal papillary mucinous neoplasm (IPMN), the most common pancreatic cystic neoplasm, is known to progress to invasive ductal adenocarcinoma. IPMNs commonly harbor activating somatic mutations in GNAS and KRAS, primarily GNAS(R201H) and KRAS(G12D). GNAS encodes the stimulatory G-protein alpha subunit (Gsalpha) that mediates a stimulatory signal to adenylyl cyclase to produce cyclic adenosine monophosphate (cAMP), subsequently activating cAMP-dependent protein kinase A. The GNAS(R201H) mutation results in constitutive activation of Gsalpha. To study the potential role of GNAS in pancreatic tumorigenesis in vivo, we generated lines of transgenic mice in which the transgene consisted of Lox-STOP-Lox (LSL) GNAS(R201H) under the control of the CAG promoter (Tg(CAG-LSL-GNAS)). These mice were crossed with pancreatic transcription factor 1a (Ptf1a)-Cre mice (Ptf1a(Cre/+)), generating Tg(CAG-LSL-GNAS);Ptf1a(Cre/+) mice. This mouse line showed elevated cAMP levels, small dilated tubular complex formation, loss of acinar cells and fibrosis in the pancreas; however, no macroscopic tumorigenesis was apparent by 2 months of age. We then crossed Tg(CAG-LSL-GNAS);Ptf1a(Cre/+) mice with LSL-Kras(G12D) mice, generating Tg(CAG-LSL-GNAS);LSL Kras(G12D);Ptf1a(Cre/+) mice. We used these mice to investigate a possible cooperative effect of GNAS(R201H) and Kras(G12D) in pancreatic tumorigenesis. Within 5 weeks, Tg(CAG-LSL-GNAS);LSL-Kras(G12D);Ptf1a(Cre/+) mice developed a cystic tumor consisting of marked dilated ducts lined with papillary dysplastic epithelia in the pancreas, which closely mimicked the human IPMN. Our data strongly suggest that activating mutations in GNAS and Kras cooperatively promote murine pancreatic tumorigenesis, which recapitulates IPMN. Our mouse model may serve as a unique in vivo platform to find biomarkers and effective drugs for diseases associated with GNAS mutations. PMID- 26257061 TI - Biodegradable interstitial release polymer loading a novel small molecule targeting Axl receptor tyrosine kinase and reducing brain tumour migration and invasion. AB - Glioblastoma multiforme (GBM) is the most common and aggressive brain tumour. The neoplasms are difficult to resect entirely because of their highly infiltration property and leading to the tumour edge is unclear. Gliadel wafer has been used as an intracerebral drug delivery system to eliminate the residual tumour. However, because of its local low concentration and short diffusion distance, patient survival improves non-significantly. Axl is an essential regulator in cancer metastasis and patient survival. In this study, we developed a controlled release polyanhydride polymer loading a novel small molecule, n butylidenephthalide (BP), which is not only increasing local drug concentration and extending its diffusion distance but also reducing tumour invasion, mediated by reducing Axl expression. First, we determined that BP inhibited the expression of Axl in a dose- and time-dependent manner and reduced the migratory and invasive capabilities of GBM cells. In addition, BP downregulated matrix metalloproteinase activity, which is involved in cancer cell invasion. Furthermore, we demonstrated that BP regulated Axl via the extracellular signal regulated kinases pathway. Epithelial-to-mesenchymal transition (EMT) is related to epithelial cells in the invasive migratory mesenchymal cells that underlie cancer progression; we demonstrated that BP reduced the expression of EMT-related genes. Furthermore, we used the overexpression of Axl in GBM cells to prove that Axl is a crucial target in the inhibition of GBM EMT, migration and invasion. In an in vivo study, we demonstrated that BP inhibited tumour growth and suppressed Axl expression in a dose-dependent manner according to a subcutaneous tumour model. Most importantly, in an intracranial tumour model with BP wafer in situ treatment, we demonstrated that the BP wafer not only significantly increased the survival rate but also decreased Axl expression, and inhibited tumour invasion. These results contribute to the development of a BP wafer for a novel therapeutic strategy for treating GBM invasion and increasing survival in clinical subjects. PMID- 26257062 TI - Somatic gene copy number alterations in colorectal cancer: new quest for cancer drivers and biomarkers. AB - Colorectal cancer (CRC) results from the accumulation of genetic alterations, and somatic copy number alterations (CNAs) are crucial for the development of CRC. Genome-wide survey of CNAs provides opportunities for identifying cancer driver genes in an unbiased manner. The detection of aberrant CNAs may provide novel markers for the early diagnosis and personalized treatment of CRC. A major challenge in array-based profiling of CNAs is to distinguish the alterations that play causative roles from the random alterations that accumulate during colorectal carcinogenesis. In this view, we systematically discuss the frequent CNAs in CRC, focusing on functional genes that have potential diagnostic, prognostic and therapeutic significance. PMID- 26257063 TI - Imipramine blue halts head and neck cancer invasion through promoting F-box and leucine-rich repeat protein 14-mediated Twist1 degradation. AB - The unique characteristic of head and neck squamous cell carcinoma (HNSCC) is that local invasion rather than distant metastasis is the major route for dissemination. Therefore, targeting the locally invasive cancer cells is more important than preventing systemic metastasis in HNSCC and other invasive predominant cancers. We previously demonstrate a specific mechanism for HNSCC local invasion: the epithelial-mesenchymal transition (EMT) regulator Twist1 represses microRNA let-7i expression, leading to the activation of the small GTPase Rac1 and engendering the mesenchymal-mode movement in three-dimensional (3D) culture. However, targeting the EMT regulator is relatively difficult because of its transcription factor nature and the strategy for confining HNSCC invasion to facilitate local treatment is limited. Imipramine blue (IB) is a newly identified anti-invasive compound that effectively inhibits glioma invasion. Here we demonstrate that in HNSCC cells, a noncytotoxic dose of IB represses mesenchymal-mode migration in two-and-a-half-dimensional/3D culture system. IB suppresses EMT and stemness of HNSCC cells through inhibition of Twist1-mediated let-7i downregulation and Rac1 activation and the EMT signalling. Mechanistically, IB inhibits reactive oxygen species-induced nuclear factor kappaB pathway activation. Importantly, IB promotes degradation of the EMT inducer Twist1 by enhancing F-box and leucine-rich repeat protein 14 (FBXL14) mediated polyubiquitination of Twist1. Together, this study demonstrates the potent anti-invasion and EMT-inhibition effect of IB, suggesting the potential of IB in treating local invasion-predominant cancers. PMID- 26257064 TI - Sustained adrenergic signaling leads to increased metastasis in ovarian cancer via increased PGE2 synthesis. AB - Adrenergic stimulation adversely affects tumor growth and metastasis, but the underlying mechanisms are not well understood. Here, we uncovered a novel mechanism by which catecholamines induce inflammation by increasing prostaglandin E2 (PGE2) levels in ovarian cancer cells. Metabolic changes in tumors isolated from patients with depression and mice subjected to restraint stress showed elevated PGE2 levels. Increased metabolites, PTGS2 and PTGES protein levels were found in Skov3-ip1 and HeyA8 cells treated with norepinephrine (NE), and these changes were shown to be mediated by ADRB2 receptor signaling. Silencing PTGS2 resulted in significantly decreased migration and invasion in ovarian cancer cells in the presence of NE and decreased tumor burden and metastasis in restraint stress orthotopic models. In human ovarian cancer samples, concurrent increased ADRB2, PTGS2 and PTGES expression was associated with reduced overall and progression-free patient survival. In conclusion, increased adrenergic stimulation results in increased PGE2 synthesis via ADRB2-Nf-kB-PTGS2 axis, which drives tumor growth and metastasis. PMID- 26257065 TI - Genome-wide lentiviral shRNA screen identifies serine/arginine-rich splicing factor 2 as a determinant of oncolytic virus activity in breast cancer cells. AB - Oncolytic human herpes simplex virus type 1 (HSV-1) shows promising treatment efficacy in late-stage clinical trials. The anticancer activity of oncolytic viruses relies on deregulated pathways in cancer cells, which make them permissive to oncolysis. To identify pathways that restrict HSV-1 KM100-mediated oncolysis, this study used a pooled genome-wide short hairpin RNA library and found that depletion of the splicing factor arginine-rich splicing factor 2 (SRSF2) leads to enhanced cytotoxicity of breast cancer cells by KM100. Serine/arginine-rich (SR) proteins are a family of RNA-binding phosphoproteins that control both constitutive and alternative pre-mRNA splicing. Further characterization showed that KM100 infection of HS578T cells under conditions of low SRSF2 leads to pronounced apoptosis without a corresponding increase in virus replication. As DNA topoisomerase I inhibitors can limit the phosphorylation of SRSF2, we combined a topoisomerase I inhibitor chemotherapeutic with KM100 and observed synergistic anticancer effect in vitro and prolonged survival of tumor bearing mice in vivo. PMID- 26257066 TI - PIAS1 is a determinant of poor survival and acts as a positive feedback regulator of AR signaling through enhanced AR stabilization in prostate cancer. AB - Novel drugs like Abiraterone or Enzalutamide, which target androgen receptor (AR) signaling to improve androgen deprivation therapy (ADT), have been developed during the past years. However, the application of these drugs is limited because of occurrence of inherent or acquired therapy resistances during the treatment. Thus, identification of new molecular targets is urgently required to improve current therapeutic prostate cancer (PCa) treatment strategies. PIAS1 (protein inhibitor of activated STAT1 (signal transducer and activator of transcription 1)) is known to be an important cell cycle regulator and PIAS1-mediated SUMOylation is essential for DNA repair. In this context, elevated PIAS1 expression has already been associated with cancer initiation. Thus, in the present study, we addressed the question of whether PIAS1 targeting can be used as a basis for an improved PCa therapy in combination with anti-androgens. We show that PIAS1 significantly correlates with AR expression in PCa tissue and in cell lines and demonstrate that high PIAS1 levels predict shorter relapse-free survival. Our patient data are complemented by mechanistic and functional in vitro experiments that identify PIAS1 as an androgen-responsive gene and a crucial factor for AR signaling via prevention of AR degradation. Furthermore, PIAS1 knockdown is sufficient to decrease cell proliferation as well as cell viability. Strikingly, Abiraterone or Enzalutamide treatment in combination with PIAS1 depletion is even more effective than single-drug treatment in multiple PCa cell models, rendering PIAS1 as a promising target protein for a combined treatment approach to improve future PCa therapies. PMID- 26257068 TI - Recurrent laryngeal nerve reinnervation in children: Acoustic and endoscopic characteristics pre-intervention and post-intervention. A comparison of treatment options. AB - OBJECTIVES/HYPOTHESIS: To establish the benefit of ansa cervicalis-recurrent laryngeal nerve reinnervation (ANSA-RLN) for the management of dysphonia secondary to unilateral vocal cord paralysis (UVCP) in children. Children treated with ANSA-RLN for the management of dysphonia secondary to unilateral vocal fold immobility will have superior acoustic, perceptual, and stroboscopic outcomes compared to injection laryngoplasty and observation. STUDY DESIGN: Retrospective case-series chart review. METHODS: Laryngeal, perceptual, and acoustic analysis of dysphonia was performed in 33 children (age 2-16 years) diagnosed with UVCP. Comparison of pre-post function for treatment groups (no treatment, injection laryngoplasty, ANSA-RLN) with additional comparison between gestational ages, age at initial evaluation, and gender were examined. Perceptual measures included Pediatric Voice Handicap Index (pVHI) and Grade, Roughness, Breathiness, Asthenia, Strain (GBRAS) perceptual rating. Objective measures included semitone (ST) range, jitter%, shimmer%, noise-to-harmonic ratio, voicing, and maximum phonation time. RESULTS: Post-treatment, pVHI, jitter%, and ST were significantly improved for ANSA-RLN subjects compared to injection subjects. Improved function (laryngeal diadochokinesis, pVHI, GRBAS, and/or acoustic) was observed in all ANSA-RLN subjects who had vocal fold paralysis as the only laryngeal diagnosis. CONCLUSIONS: This study presents one of the largest studies of pediatric vocal fold paralysis diagnosis and treatment. The study looks at the spectrum of function in patients with UVCP and looks at the outcomes of options: no treatment, injection laryngoplasty, and ANSA-RLN. Although surgical outcomes vary, both injection laryngoplasty and ANSA-RLN show benefit in laryngeal function, voice stability, voice capacity, perceptual rating, and pVHI scores. Both injection laryngoplasty and ANSA-RLN showed improvements post-treatment, and should be considered for management of pediatric UVCP. However, the ANSA-RLN group showed better and longer-lasting perceptual and acoustic parameters in comparison with the injection and control groups. Reinnervation, even long term after the onset of vocal fold paralysis, should be considered a viable permanent treatment for pediatric UVCP. PMID- 26257069 TI - Dual lifetime referencing enables pH-control for oxidoreductions in hydrogel stabilized biphasic reaction systems. AB - pH-shifts are a serious challenge in cofactor dependent biocatalytic oxidoreductions. Therefore, a pH control strategy was developed for reaction systems, where the pH value is not directly measurable. Such a reaction system is the biphasic aqueous-organic reaction system, where the oxidoreduction of hydrophobic substrates in organic solvents is catalysed by hydrogel-immobilized enzymes, and enzyme-coupled cofactor regeneration is accomplished via formate dehydrogenase, leading to a pH-shift. Dual lifetime referencing (DLR), a fluorescence spectroscopic method, was applied for online-monitoring of the pH value within the immobilizates during the reaction, allowing for a controlled dosage of formic acid. It could be shown that by applying trisodium 8 hydroxypyrene-1, 3, 6-trisulfonate as pH indicator and Ru(II) tris(4, 7-diphenyl 1, 10-phenantroline) (Ru[dpp]) as a reference luminophore the control of the pH value in a macroscopic gel-bead-stabilized aqueous/organic two phase system in a range of pH 6.5 to 8.0 is possible. An experimental proof of concept could maintain a stable pH of 7.5 +/- 0.15 during the reaction for at least 105 h. With these results, it could be shown that DLR is a powerful tool for pH-control within reaction systems with no direct access for conventional pH-measurement. PMID- 26257070 TI - Narrative review of current context of malaria and management strategies in Uganda (Part I). AB - In accordance with international targets, the Uganda National Malaria Control Strategic Plan established specific targets to be achieved by 2010. For children under five, this included increasing the number of children sleeping under mosquito nets and those receiving a first-line antimalarial to 85%, and decreasing case fatality to 2%. This narrative review offers contextual information relevant to malaria management in Uganda since the advent of artemisinin combination therapy (ACT) as first-line antimalarial treatment in 2004. A comprehensive search using key words and phrases was conducted using the web search engines Google and Google Scholar, as well as the databases of PubMed, ERIC, EMBASE, CINAHL, OvidSP (MEDLINE), PSYC Info, Springer Link, Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Database of Systematic Reviews were searched. A total of 147 relevant international and Ugandan literature sources meeting the inclusion criteria were included. This review provides an insightful understanding on six topic areas: global and local priorities, malarial pathology, disease burden, malaria control, treatment guidelines for uncomplicated malaria, and role of the health system in accessing antimalarial medicines. Plasmodium falciparum remains the most common cause of malaria in Uganda, with children under five being most vulnerable due to their underdeveloped immunity. While international efforts to scale up malaria control measures have resulted in considerable decline in malaria incidence and mortality in several regions of sub-Saharan Africa, this benefit has yet to be substantiated for Uganda. At the local level, key initiatives have included implementation of a new antimalarial drug policy in 2004 and strengthening of government health systems and programs. Examples of such programs include removal of user fees, training of frontline health workers, providing free ACT from government systems and subsidized ACT from licensed private outlets, and introduction of the integrated community case management program to bring diagnostics and treatment for malaria, pneumonia and diarrhea closer to the community. However despite notable efforts, Uganda is far from achieving its 2010 targets. Several challenges in the delivery of care and treatment remain, with those most vulnerable and living in rural settings remaining at greatest risk from malaria morbidity and mortality. PMID- 26257067 TI - Targeting BCL-2 to enhance vulnerability to therapy in estrogen receptor-positive breast cancer. AB - The last three decades have seen significant progress in our understanding of the role of the pro-survival protein BCL-2 and its family members in apoptosis and cancer. BCL-2 and other pro-survival family members including Mcl-1 and BCL-XL have been shown to have a key role in keeping pro-apoptotic 'effector' proteins BAK and BAX in check. They also neutralize a group of 'sensor' proteins (such as BIM), which are triggered by cytotoxic stimuli such as chemotherapy. BCL-2 proteins therefore have a central role as guardians against apoptosis, helping cancer cells to evade cell death. More recently, an increasing number of BH3 mimetics, which bind and neutralize BCL-2 and/or its pro-survival relatives, have been developed. The utility of targeting BCL-2 in hematological malignancies has become evident in early-phase studies, with remarkable clinical responses seen in heavily pretreated patients. As BCL-2 is overexpressed in ~75% of breast cancer, there has been growing interest in determining whether this new class of drug could show similar promise in breast cancer. This review summarizes our current understanding of the role of BCL-2 and its family members in mammary gland development and breast cancer, recent progress in the development of new BH3 mimetics as well as their potential for targeting estrogen receptor-positive breast cancer. PMID- 26257071 TI - Analysis of sitting forces on stationary chairs for daily activities. AB - No literature related to the study of sitting forces on chairs sat on by people who weighed over 136 kg was found. The Business Institutional Furniture Manufactures Association needs force data for development of performance test standards to test chairs for users who weigh up to 181 kg. 20 participants who weighed from 136 to 186 kg completed 6 tasks on an instrumented chair in the sequence of sitting down, remaining seated and rising. Effects of sitting motion, armrest use and seat cushion thickness on vertical sitting forces and centre-of force were investigated. Results indicated hard sitting down yielded the highest sitting force of 213% in terms of participants' body weights. Armrest use affected sitting forces of normal sitting down, but not of rising and hard sitting down. Cushion thickness affected sitting forces of normal and hard sitting down and shifting, but not of rising, static seating or stretching backward situations. Practitioner Summary: Results of the sitting force and centre-of-force data obtained for this research can help furniture manufacturers develop new product performance test standards for creating reliable engineering design and manufacturing quality and durable products to meet a niche market need. PMID- 26257072 TI - Simultaneous Electrochemical Reduction and Delamination of Graphene Oxide Films. AB - Here we report an electrochemical method to simultaneously reduce and delaminate graphene oxide (G-O) thin films deposited on metal (Al and Au) substrates. During the electrochemical reaction, interface charge transfer between the G-O thin film and the electrode surface was found to be important in eliminating oxygen containing groups, yielding highly reduced graphene oxide (rG-O). In the meantime, hydrogen bubbles were electrochemically generated at the rG-O film/electrode interface, propagating the film delamination. Unlike other metal based G-O reduction methods, the metal used here was either not etched at all (for Au) or etched a small amount (for Al), thus making it possible to reuse the substrate and lower production costs. The delaminated rG-O film exhibits a thickness-dependent degree of reduction: greater reduction is achieved in thinner films. The thin rG-O films having an optical transmittance of 90% (lambda = 550 nm) had a sheet resistance of 6390 +/- 447 Omega/? (ohms per square). rG-O-based stretchable transparent conducting films were also demonstrated. PMID- 26257073 TI - Comparison of Aroma-Active Volatiles in Oolong Tea Infusions Using GC Olfactometry, GC-FPD, and GC-MS. AB - The aroma profile of oolong tea infusions (Dongdingwulong, DDWL; Tieguanyin, TGY; Dahongpao, DHP) were investigated in this study. Gas chromatography-olfactometry (GC-O) with the method of aroma intensity (AI) was employed to investigate the aroma-active compounds in tea infusions. The results presented forty-three, forty five, and forty-eight aroma-active compounds in the TGY, DHP, and DDWL infusions, including six, seven, and five sulfur compounds, respectively. In addition, the concentration of volatile compounds in the tea infusions was further quantitated by solid phase microextraction-gas chromatography (SPME)-GC-MS and SPME-GC-flame photometric detection (FPD). Totally, seventy-six and thirteen volatile and sulfur compounds were detected in three types of tea infusions, respectively. Quantitative results showed that forty-seven aroma compounds were at concentrations higher than their corresponding odor thresholds. On the basis of the odor activity values (OAVs), 2-methylpropanal (OAV: 230-455), 3-methylbutanal (1-353), 2-methylbutanal (34-68), nerolidol (108-184), (E)-2-heptenal (148-294), hexanal (134-230), octanal (28-131), beta-damascenone (29-59), indole (96-138), 6 methyl-5-hepten-2-one (34-67), (R)-(-)-linalool (63-87), and dimethyl sulfide (7 1320) presented relatively higher OAVs than those of other compounds, indicating the importance of these compounds in the overall aroma of tea infusions. PMID- 26257074 TI - Real-time in situ monitoring via europium emission of the photo-release of antitumor cisplatin from a Eu-Pt complex. AB - A water-soluble light-responsive antitumor agent, PtEuL, based on a cisplatin linked europium-cyclen complex has been synthesized and evaluated for controlled cisplatin release by linear/two-photon excitation in vitro with concomitant turn on and long-lived europium emission as a responsive traceable signal. PMID- 26257075 TI - Diagnosis and treatment of Merkel Cell Carcinoma. European consensus-based interdisciplinary guideline. AB - Merkel cell carcinoma (MCC) is a rare tumour of the skin of neuro-endocrine origin probably developing from neuronal mechanoreceptors. A collaborative group of multidisciplinary experts form the European Dermatology Forum (EDF), The European Association of Dermato-Oncology (EADO) and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on MCC diagnosis and management, based on a critical review of the literature, existing guidelines and expert's experience. Clinical features of the cutaneous/subcutaneous nodules hardly contribute to the diagnosis of MCC. The diagnosis is made by histopathology, and an incisional or excisional biopsy is mandatory. Immunohistochemical staining contributes to clarification of the diagnosis. Initial work-up comprises ultrasound of the loco-regional lymph nodes and total body scanning examinations. The primary tumour should be excised with 1 2cm margins. In patients without clinical evidence of regional lymph node involvement, sentinel node biopsy is recommended, if possible, and will be taken into account in a new version of the AJCC classification. In patients with regional lymph node involvement radical lymphadenectomy is recommended. Adjuvant radiotherapy might be considered in patients with multiple affected lymph nodes of extracapsular extension. In unresectable metastatic MCC mono- or poly chemotherapy achieve high remission rates. However, responses are usually short lived. Treatment within clinical trials is regarded as a standard of care in disseminated MCC. PMID- 26257077 TI - Tailoring the Optical Absorption of Water-Stable Zr(IV)- and Hf(IV)-Based Metal Organic Framework Photocatalysts. AB - New Zr(IV)- and Hf(IV)-based metal-organic framework photocatalysts, termed VNU-1 and VNU-2 (where VNU = Vietnam National University), were synthesized and their resulting structures fully characterized. By employing a highly pi-conjugated linker, namely 1,4-bis(2-[4-carboxyphenyl]ethynyl)benzene, the optical absorption properties were effectively red-shifted into the visible light region. This strategy, coupled with the high water stability of the materials, led to enhanced MOF-driven photocatalytic degradation, under ultraviolet-visible light, of organic dye pollutants commonly found in wastewater. PMID- 26257078 TI - Characterization of Atypical Off-Flavor Compounds in Natural Cork Stoppers by Multidimensional Gas Chromatographic Techniques. AB - Natural cork stoppers with sensory deviations other than the typical cork taint were subgrouped according to their sensory descriptions and compared with unaffected control cork stoppers. The assessment of purge and trap extracts obtained from corresponding cork soaks was performed by heart-cut multidimensional gas chromatography-olfactometry (MDGC-O). The identification of compounds responsible for atypical cork taint detected in MDGC-O was further supported with additional multidimensional GC analysis in combination with mass spectrometric detection. Geosmin and 2-methylisoborneol were mainly found in cork stoppers described as moldy and cellarlike; 3-isopropyl-2-methoxypyrazine and 3 isobutyl-2-methoxypyrazine were found in cork stoppers described with green attributes. Across all cork subgroups, the impact compound for typical cork taint, 2,4,6-trichloroanisole (TCA), was present and is therefore a good marker for cork taint in general. Another potent aroma compound, 3,5-dimethyl-2 methoxypyrazine (MDMP), was also detected in each subgroup, obviously playing an important role with regard to the atypical cork taint. Sensory deviations possibly affecting the wine could be generated by MDMP and its presence should thus be monitored in routine quality control. PMID- 26257076 TI - STIM1 accelerates cell senescence in a remodeled microenvironment but enhances the epithelial-to-mesenchymal transition in prostate cancer. AB - The importance of store-operated Ca(2+) entry (SOCE) and the role of its key molecular regulators, STIM1 and ORAI1, in the development of cancer are emerging. Here, we report an unexpected dual function of SOCE in prostate cancer progression by revealing a decrease in the expression of STIM1 in human hyperplasia and tumor tissues of high histological grade and by demonstrating that STIM1 and ORAI1 inhibit cell growth by arresting the G0/G1 phase and enhancing cell senescence in human prostate cancer cells. In addition, STIM1 and ORAI1 inhibited NF-kappaB signaling and remodeled the tumor microenvironment by reducing the formation of M2 phenotype macrophages, possibly creating an unfavorable tumor microenvironment and inhibiting cancer development. However, STIM1 also promoted cell migration and the epithelial-to-mesenchymal transition by activating TGF-beta, Snail and Wnt/beta-Catenin pathways. Thus, our study revealed novel regulatory effects and the mechanisms by which STIM1 affects cell senescence, tumor migration and the tumor microenvironment, revealing that STIM1 has multiple functions in prostate cancer cells. PMID- 26257079 TI - Electrochemically triggered release of human insulin from an insulin-impregnated reduced graphene oxide modified electrode. AB - An electrochemical insulin-delivery system based on reduced graphene oxide impregnated with insulin is described. Upon application of a potential pulse of 0.8 V for 30 min, up to 70 +/- 4% of human insulin was released into a physiological medium while preserving its biological activity. PMID- 26257080 TI - Immunosenescence and the ability to survive bacterial infection in the red flour beetle Tribolium castaneum. AB - In most animals, ageing is associated with a decline in immune function (immune senescence). However, different components of the immune system seem to age differentially, and many studies do not measure the ultimate fitness consequences of immune function after infection. Previous work shows that immune function may be traded off with other fitness components such as reproduction. It is possible that age alters the nature of these trade-offs, particularly in conjunction with factors such as gender and mating that can also affect investment in immune function. We tested the impact of age, sex and mating on post-infection survivorship in Tribolium castaneum flour beetles, as well as the components of baseline constitutive innate immunity and external (secreted) immune function in uninfected individuals. We also tested whether the reproductive ability of uninfected females is traded off with immune function (baseline innate and external immunity) and post-infection survivorship across age groups. We found that age, sex and mating significantly affected immune components and infection outcome, although the magnitude and nature of the impact varied in each case. We found that older beetles were more susceptible to infection by the pathogen Bacillus thuringiensis even though major components of the constitutive innate immune defence (antibacterial and phenoloxidase activity) remained unchanged or improved with age. Thus, these aspects of innate immunity cannot explain the observed decline in post-infection survival of older beetles. We did not find trade-offs between the reproductive ability of uninfected females and their immune function. In contrast to innate immunity, external immunity showed an overall decline with age but was also affected by sex and mating. Finally, we show that bacterial infection alters external immunity via complex interactions between age, sex and mating status. Our work uncovers novel interactions between age, sex and mating that can determine the evolution and outcome of immunosenescence by affecting the time course of relative investment in different immune and fitness components. PMID- 26257081 TI - Does the disparity in baseline characteristics of patients undergoing transcatheter aortic valve replacement with 23 mm vs. 26 mm valves impact clinical outcome? AB - OBJECTIVES: We sought to identify if baseline characteristic differences in patients who receive a 23 mm vs. 26 mm valve impact clinical outcomes. BACKGROUND: Transcatheter aortic valve replacement (TAVR) is currently an approved therapy for patients with severe aortic stenosis who are considered inoperable or are at high risk. METHODS: We retrospectively examined baseline characteristics and outcomes of patients receiving a 23 mm (n = 132) vs. 26 mm valve (n = 81) via the transfemoral approach. RESULTS: Gender (P < 0.01), previous coronary artery bypass surgery (P < 0.01), history of atrial fibrillation (P = 0.04), and mean Society of Thoracic Surgeons (STS) score (P < 0.01) were significantly different between groups. There were no significant differences in the rates of minor/major vascular complications (2.2 vs. 3.7%, P = 0.68 and 13.0 vs. 12.3%, P = 0.89, respectively). Bleeding complications were also comparable (major bleed 2.3 vs. 1%, P >0.99, minor bleed 19.0 vs. 22.0%, P = 0.67 and life threatening bleed 7.0 vs. 5.0%, P = 0.77). In-hospital death (6.0 vs. 5.0%, P >0.99), 30-day all-cause death (7.6 vs. 6.2%, P = 0.69), and all cause death at 1 year (17.4 vs. 25.9%, P = 0.13) were also similar between groups. Gender, valve size, previous coronary bypass surgery and atrial fibrillation were not independently associated with mortality; however, on multivariate analysis STS score was (HR 1.11; 95% CI 1.02-1.19; P = 0.01). CONCLUSION: Patients undergoing TAVR with 23 and 26 mm valves have similar clinical outcomes despite significant differences in baseline characteristics. (c) 2015 Wiley Periodicals, Inc. PMID- 26257082 TI - PreImplantation Factor (PIF*) endogenously prevents preeclampsia: Promotes trophoblast invasion and reduces oxidative stress. AB - Preeclampsia is a unique pregnancy disorder whose patho-physiology is initiated early in gestation, while clinical manifestations typically occur in mid-to-late pregnancy. Thus, prevention should optimally be initiated in early gestation. The intimate interaction between PIF, secreted early by viable embryos, and its host mother provides insight into putative mechanisms of preeclampsia prevention. PIF is instrumental at the two critical events underlying preeclampsia. At first, shallow implantation leads to impaired placentation, oxidative stress, protein misfolding, and endothelial dysfunction. Later in gestation, hyper-oxygenation due to overflow of maternally derived oxygenated blood compromises the placenta. The first is likely involved in early preeclampsia occurrence due to reduced effectiveness of trophoblast/uterus interaction. The latter is observed with later-onset preeclampsia, caused by a breakdown in placental blood flow regulation. We reported that 1. PIF promotes implantation, endometrium receptivity, trophoblast invasion and increases pro-tolerance trophoblastic HLA-G expression and, 2. PIF protects against oxidative stress and protein misfolding, interacting with specific targets in embryo, 3. PIF regulates systemic immunity to reduce oxidative stress. Using PIF as an early preventative preeclampsia intervention could ameliorate or even prevent the disease, whose current main solution is early delivery. PMID- 26257083 TI - Screening of Carotenoids in Tomato Fruits by Using Liquid Chromatography with Diode Array-Linear Ion Trap Mass Spectrometry Detection. AB - This paper presents an analytical strategy for a large-scale screening of carotenoids in tomato fruits by exploiting the potentialities of the triple quadrupole-linear ion trap hybrid mass spectrometer (QqQLIT). The method involves separation on C30 reversed-phase column and identification by means of diode array detection (DAD) and atmospheric pressure chemical ionization-mass spectrometry (APCI-MS). The authentic standards of six model compounds were used to optimize the separative conditions and to predict the chromatographic behavior of untargeted carotenoids. An information dependent acquisition (IDA) was performed with (i) enhanced-mass scan (EMS) as the survey scan, (ii) enhanced resolution (ER) scan to obtain the exact mass of the precursor ions (16-35 ppm), and (iii) enhanced product ion (EPI) scan as dependent scan to obtain structural information. LC-DAD-multiple reaction monitoring (MRM) chromatograms were also acquired for the identification of targeted carotenoids occurring at low concentrations; for the first time, the relative abundance between the MRM transitions (ion ratio) was used as an extra tool for the MS distinction of structural isomers and the related families of geometrical isomers. The whole analytical strategy was high-throughput, because a great number of experimental data could be acquired with few analytical steps, and cost-effective, because only few standards were used; when applied to characterize some tomato varieties ('Tangerine', 'Pachino', 'Datterino', and 'Camone') and passata of 'San Marzano' tomatoes, our method succeeded in identifying up to 44 carotenoids in the 'Tangerine'" variety. PMID- 26257084 TI - Thermoluminescence signal in K-feldspar grains: Revisited. AB - Recent work has shown that infrared stimulated luminescence (IRSL) signals in sedimentary coarse-grain K-feldspars are derived mainly from high temperature thermoluminescence (TL) peaks around 400 degrees C, and the fading components of the IRSL signal can be preferentially removed by prior IR stimulation at relatively low temperature. Considering the complexity of TL signal for very old samples, we may choose non-fading components from K-feldspar TL signals using the combination of optical and thermal activation methods. This paper examines a protocol of post-IR isothermal TL (i.e. pIRITL) signal for sedimentary coarse grain K-feldspars, which results from isothermal TL measurements following elevated temperature IR bleaching. We show that a sum of two exponential decay functions can fit well to the pIRITL decay curves, and both the holding temperature for isothermal TL measurements and the prior elevated temperature IR bleaching can affect greatly the fast components of pIRITL signal. The dose response ranges of pIRITL signal are wider than those of post-IR IRSL signals, but the relative high residual pIRITL signal means that it is not appropriate for dating young samples. It is expected that one isothermal TL signal for K-feldspar measured at ~400 degrees C following IR bleaching at 290 degrees C (i.e. pIRITL400) is useful for dating very old samples. PMID- 26257085 TI - Comparison of percutaneous device closure versus surgical closure of peri membranous ventricular septal defects: A systematic review and meta-analysis. AB - BACKGROUND: While percutaneous device closure (PDC) is a first-line therapy for isolated muscular ventricular septal defects (mVSD), surgery is still the preferred approach for peri-membranous ventricular septal defects (pmVSD). OBJECTIVE: We sought to compare the outcomes of percutaneous versus open surgical closure of pmVSDs. METHODS: PubMed, Cochrane Library, and Web of Science databases were searched through October 15, 2014 for English language studies comparing outcomes of PDC with surgical closure of pmVSDs. Study quality, publication bias, and heterogeneity were assessed. A meta-analysis of selected studies was performed using a random effects model. Comparison was done for early (<1 month) safety and efficacy outcomes. RESULTS: Seven studies with a total of 3,134 patients (PDC = 1,312, surgery = 1,822) were identified. Patients in the PDC group were older than those treated surgically (mean age 12.2 vs. 5.5 years, respectively). In six out of seven studies, the mean VSD size was found to be comparable between the treatment arms (PDC 4.9 mm vs. surgery 6.0 mm). Males represented 52% of patients in either group. Follow-up ranged from 5 to 42 months. No significant differences were observed between PDC vs. surgery in terms of procedural success rate [relative risk (RR): 1.00, confidence interval (CI): 0.99-1.00; P = 0.67]. Combined safety end points for major complications (early death/reoperation/permanent pacemaker) were similar in both groups (RR: 0.55, CI: 0.23-1.35; P = 0.19) as were as other outcomes like post-procedure significant residual shunt (RR: 0.69, CI: 0.29-1.68; P = 0.41), significant valvular (aortic/tricuspid) regurgitation (RR: 0.70, CI: 0.26-1.86; P = 0.47), and advanced heart block (RR: 0.99, CI: 0.46-2.14; P = 0.98). The need for blood transfusion (RR: 0.02, CI: 0.00-0.05; P < 0.001) and duration of hospital stay [standard mean difference (SMD) -2.17 days, CI: -3.12 to -1.23; P < 0.001] were significantly reduced in the PDC group. CONCLUSION: Percutaneous closure of pmVSD when performed in a selected subgroup of patients is associated with similar procedural success rate without increased risk of significant valvular regurgitation or heart block when compared with surgical closure. PMID- 26257086 TI - Emotional reactivity to social stimuli in patients with eating disorders. AB - Patients with eating disorders often display a wide range of difficulties in psychosocial functioning. Most of the studies on this subject have focused on theory of mind; however, little is known about the subjective emotional reactivity of patients to social situations. The aim of this study was to evaluate the patients' perceptions of their own emotions when viewing pictures with social content. Emotional reactivity was assessed in 85 women (29 with anorexia nervosa, 28 with bulimia nervosa, and 28 healthy controls) by using 30 images from the International Affective Picture System. Images were divided into categories based on its social content and its emotional valence. The emotional response was evaluated through the Self-Assessment Manikin. Patients with bulimia nervosa presented higher arousal and lower control when viewing images with social content of pleasant, unpleasant, and neutral valence. Patients with anorexia nervosa reported higher arousal and lower control only for social images with neutral valence. There were no differences between groups for the control images. The finding of specific differences in emotional reactivity to pictures with social content contributes to a more accurate understanding of the difficulties of patients in social situations. PMID- 26257087 TI - Factors contributing to social cognition impairment in borderline personality disorder and schizophrenia. AB - Social cognition (SC) deficits have been described both in patients with schizophrenia and borderline personality disorder (BPD). However, while the former tend towards simplistic mental state attributions (undermentalizing), the latter are more likely to make overly complex mental state inferences (overmentalizing). Performance on complex SC tasks has been shown to correlate with neurocognitive ability, emotion perception, a history of trauma, and overconfidence in errors. However, it is unclear how these factors relate to different aspects of SC deficits. Aim of the present study was to examine the pathways of SC impairment by investigating performance profiles and their predictors comparatively in BPD and schizophrenia. Participants were 44 patients with BPD, 36 patients with schizophrenia, and 38 healthy controls. Undermentalizing and overmentalizing were assessed with an ecologically valid SC task. Patients with BPD exhibited increased overmentalizing, whereas patients with schizophrenia showed a more extensive deficit pattern, their main error type being undermentalizing. Overconfidence in errors was the most important predictor for overmentalizing, while undermentalizing depended mainly on verbal memory and emotion perception. Thus, BPD und schizophrenia exhibited different SC impairment patterns, and different types of SC errors were predicted by different factors. These findings have implications for the optimization of treatment approaches. PMID- 26257088 TI - Expanding the utility of the malignant self-regard construct. AB - The empirical and theoretical literature suggest that several proposed personality disorders (PDs) - Masochistic/Self-Defeating, Depressive, and Vulnerably Narcissistic - may be related through a common self-representation know as Malignant Self-Regard (MSR). To assess this construct, the MSR Questionnaire (MSRQ) was developed. Though its initial psychometric properties were very strong, the present study extended these findings by examining the relationship of the MSRQ with measures of other PDs and depressive subtypes, and by establishing four-week and eight-week test-retest reliability in two samples (Ns=840, 911) of undergraduate students. The MSRQ was internally consistent and temporally stable over four and eight weeks. It was positively correlated with measures of introjective and anaclitic depression, measures of Self-Defeating, Depressive, and Vulnerably Narcissistic personalities (rs ranging between 0.60 and 0.82), and other select PDs. After controlling for depressive symptoms and self-esteem, the highest remaining partial correlations were with Vulnerably Narcissistic, Self-Defeating, Depressive, and Avoidant personalities. A factor analysis of the MSRQ with measures of other PDs yielded a two-factor solution, with MSR loading most strongly on one factor, along with Vulnerably Narcissistic, Avoidant, Depressive, and Self-Defeating personalities. It is concluded that MSR is a psychometrically supported construct that might have good clinical utility in explaining personality pathology that has historically been difficult to assess. PMID- 26257089 TI - Is energy a stronger indicator of mood for those with bipolar disorder compared to those without bipolar disorder? AB - Theory and research indicate that activity is fundamental to mood episodes in bipolar disorder (BD), yet researchers have not tested whether energy is more closely tethered to mood in BD compared to those without BD. Eighty-seven participants (13 with self-reported BD) completed 4396 energy and mood ratings through a mood-monitoring application. Mixed modeling analyses indicated that low energy, but not high energy, was related to mood within the BD group. Low energy could provide a strong and easily recognized indicator of negative mood states in persons with BD. PMID- 26257090 TI - Disruptions to processing of self referential emotional material are associated with positive symptoms of schizotypy. AB - The current experiment examined emotional processing difficulties related to self referential material in high schizotypal individuals employing the mnemic neglect paradigm. Participants read about behaviors, in reference to themselves, that were either central or peripheral, and positive or negative, before recalling those behaviors. Levels of self reported unusual experiences and cognitive disorganization were associated with reduced recall of central positive behaviors, and increased recall of central negative behaviors. These findings are discussed in terms of emotional processing of stimuli in schizotypy, and suggest that high schizotypal individuals are insensitive to emotional self referential material. PMID- 26257091 TI - Aberrant response inhibition and task switching in psychopathic individuals. AB - Deficits in cognitive control have been considered a core dysfunction of psychopathy, responsible for disrupted self-control. We investigated cognitive control impairments, including difficulties with task switching, failure of response inhibition, and inability to adjust speed of responding. Participants included 16 subjects with psychopathic traits (Ps), and 22 healthy controls (HCs). We recorded behavioral responses during a Task Switching paradigm, a probe of flexible behavioral adaptation to changing contexts; and a Go/NoGo Task, which assesses response inhibition and indexes behavioral impulsivity. During task switching, Ps evidenced impairments shifting set when conflicting (incongruent) information was presented, but performed as well as HCs in the absence of such conflict. In addition, when they encountered these difficulties, they failed to adjust their speed of responding. Ps presented also with deficits in response inhibition, with many commission errors on the Go/NoGo Task. This study identified impairments in response inhibition and in set shifting in psychopathic individuals. When shifting set, they evidenced difficulties refocusing on a new task when it was incongruent with the previous task. These deficits interfere with regulation of ongoing behavior and disrupt self-regulation. Our findings suggest abnormal neural processing during suppression of inappropriate responses in psychopathic individuals. PMID- 26257093 TI - Anaplastic Large Cell Lymphoma in Central America: A Report From the Central American Association of Pediatric Hematology Oncology (AHOPCA). AB - BACKGROUND: Although anaplastic large cell lymphoma (ALCL) is curable in high income countries (HIC), data from low- and middle-income countries (LMIC) are lacking. We therefore conducted a retrospective study of the Central American Association of Pediatric Hematology Oncology (AHOPCA) experience in treating ALCL. PROCEDURE: We included all patients age <18 years newly diagnosed with ALCL treated between 2000 and 2013 in seven AHOPCA institutions. Retrospective data were extracted from the Pediatric Oncology Network Database. RESULTS: Thirty-one patients met inclusion criteria. Twenty-five (81%) had advanced disease (stages III and IV), six (19%) were treated on the APO (doxorubicin, prednisone, vincristine) regimen, 15 (49%) on multi-agent chemotherapy designed for T-cell lineage malignancies (GuatALCL protocol), and 10 (32%) on BFM-based treatment regimens. Five-year overall event-free survival and overall survival were, respectively, 67.1 +/- 8.6% and 66.7 +/- 8.7%. All 10 events occurred in patients treated on BFM-based treatment regimens or the GuatALCL protocol, none on APO treatment: two patients experienced relapse, six treatment related mortality (TRM), and two abandonment. CONCLUSIONS: Treatment of ALCL in countries with limited resources is feasible with similar outcomes as in HIC, though the causes of treatment failure differ. Less intensive regimens may be preferable in order to decrease TRM and improve outcomes. Prospective clinical trials determining the ideal treatment for LMIC children with ALCL are necessary. PMID- 26257092 TI - Emotional trait and memory associates of sleep timing and quality. AB - Poor ability to remember the extinction of conditioned fear, elevated trait anxiety, and delayed or disrupted nocturnal sleep are reported in anxiety disorders. The current study examines the interrelationship of these factors in healthy young-adult males. Skin-conductance response was conditioned to two differently colored lamps. One color but not the other was then extinguished. After varying delays, both colors were presented to determine extinction recall and generalization. Questionnaires measured sleep quality, morningness eveningness, neuroticism and trait anxiety. A subset produced a mean 7.0 nights of actigraphy and sleep diaries. Median split of mean sleep midpoint defined early- and late-"sleep timers". Extinction was more rapidly learned in the morning than evening only in early timers who also better generalized extinction recall. Extinction recall was greater with higher sleep efficiency. Sleep efficiency and morningness were negatively associated with neuroticism and anxiety. However, neuroticism and anxiety did not predict extinction learning, recall or generalization. Therefore, neuroticism/anxiety and deficient fear extinction, although both associated with poor quality and late timing of sleep, are not directly associated with each other. Elevated trait anxiety, in addition to predisposing directly to anxiety disorders, may thus also indirectly promote such disorders by impairing sleep and, consequently, extinction memory. PMID- 26257095 TI - From spent Mg/Al layered double hydroxide to porous carbon materials. AB - Adsorption has been considered as an efficient method for the treatment of dye effluents, but proper disposal of the spent adsorbents is still a challenge. This work attempts to provide a facile method to reutilize the spent Mg/Al layered double hydroxide (Mg/Al-LDH) after the adsorption of orange II (OII). Herein, the spent hybrid was carbonized under the protection of nitrogen, and then washed with acid to obtain porous carbon materials. Thermogravimetric analysis results suggested that the carbonization could be well achieved above 600 degrees C, as mass loss of the spent hybrid gradually stabilized. Therefore, the carbonization process was carried out at 600, 800, and 1000 degrees C, respectively. Scanning electron microscope showed that the obtained carbon materials possessed a crooked flaky morphology. Nitrogen adsorption-desorption results showed that the carbon materials had large BET surface area and pore volume, e.g., 1426 m(2)/g and 1.67 cm(3)/g for the sample carbonized at 800 degrees C. Moreover, the pore structure and surface chemistry compositions were tunable, as they were sensitive to the temperature. Toluene adsorption results demonstrated that the carbon materials had high efficiency in toluene removal. This work provided a facile approach for synthesizing porous carbon materials using spent Mg/Al-LDH. PMID- 26257094 TI - Enhancement effects of reducing agents on the degradation of tetrachloroethene in the Fe(II)/Fe(III) catalyzed percarbonate system. AB - In this study, the effects of reducing agents on the degradation of tetrachloroethene (PCE) were investigated in the Fe(II)/Fe(III) catalyzed sodium percarbonate (SPC) system. The addition of reducing agents, including hydroxylamine hydrochloride, sodium sulfite, ascorbic acid and sodium ascorbate, accelerated the Fe(III)/Fe(II) redox cycle, leading to a relatively steady Fe(II) concentration and higher production of free radicals. This, in turn, resulted in enhanced PCE oxidation by SPC, with almost complete PCE removal obtained for appropriate Fe and SPC concentrations. The chemical probe tests, using nitrobenzene and carbon tetrachloride, demonstrated that HO was the predominant radical in the system and that O2(-) played a minor role, which was further confirmed by the results of electron spin resonance measurements. PCE degradation decreased significantly with the addition of isopropanol, a HO scavenger, supporting the hypothesis that HO was primarily responsible for PCE degradation. It is noteworthy that Cl(-) release was slightly delayed in the first 20 min, indicating that intermediate products were produced. However, these intermediates were further degraded, resulting in the complete conversion of PCE to CO2. In conclusion, the use of reducing agents to enhance Fe(II)/Fe(III) catalyzed SPC oxidation appears to be a promising approach for the rapid degradation of organic contaminants in groundwater. PMID- 26257096 TI - Denitrifying capability and community dynamics of glycogen accumulating organisms during sludge granulation in an anaerobic-aerobic sequencing batch reactor. AB - Denitrifying capability of glycogen accumulating organisms (GAOs) has received great attention in environmental science and microbial ecology. Combining this ability with granule processes would be an interesting attempt. Here, a laboratory-scale sequencing batch reactor (SBR) was operated to enrich GAOs and enable sludge granulation. The results showed that the GAO granules were cultivated successfully and the granules had denitrifying capability. The batch experiments demonstrated that all NO3(-)-N could be removed or reduced, some amount of NO2(-)-N were accumulated in the reactor, and N2 was the main gaseous product. SEM analysis suggested that the granules were tightly packed with a large amount of tetrad-forming organisms (TFOs); filamentous bacteria served as the supporting structures for the granules. The microbial community structure of GAO granules was differed substantially from the inoculant conventional activated sludge. Most of the bacteria in the seed sludge grouped with members of Proteobacterium. FISH analysis confirmed that GAOs were the predominant members in the granules and were distributed evenly throughout the granular space. In contrast, PAOs were severely inhibited. Overall, cultivation of the GAO granules and utilizing their denitrifying capability can provide us with a new approach of nitrogen removal and saving more energy. PMID- 26257097 TI - Hepatitis E seroprevalence in inflammatory bowel disease. AB - BACKGROUND AND AIMS: Several cases of chronic infection by hepatitis E virus (HEV) in immunocompromised patients have been described recently. Patients with inflammatory bowel disease (IBD) are frequently immunocompromised because of the disease itself or due to therapy. Our aims were to determine HEV seroprevalence in patients with IBD and to detect possible chronic forms. METHODS: We prospectively selected a random sample of 87 patients from our local IBD clinic database at the Gastroenterology Service, Hospital Ramon y Cajal, in Madrid, Spain. Patients completed an oral epidemiologic interview. Anti-HEV IgG and IgM antibodies and HEV-RNA were determined. Medical records were reviewed, focusing on drug exposure. RESULTS: We included 87 patients, with a mean age of 44.7 years (SD 16) and a mean of 10.4 years (SD 8.4) with IBD. Fifty-seven percent were diagnosed with Crohn's disease, 41.4% with ulcerative colitis and 1.1% with unclassified IBD. A total of 41.4% had received systemic glucocorticoids for more than 3 months, 32.2% had been treated with thiopurines, 16.1% with biological drugs, and 3.4% with methotrexate. Anti HEV-IgM was determined in 75 patients and IgG in 80, and were positive in 2.7% and 1.3%, respectively. HEV-RNA was analyzed in a random subset of 46 patients, and all determinations were negative. Therefore, no case of chronic HEV infection was detected. CONCLUSIONS: We found a low HEV seroprevalence of just 1.14% in patients with IBD, similar to that in the general population. This could be due to the lower degree of immunosuppression in this group, or to different dietary habits. PMID- 26257098 TI - Understanding inflammatory bowel disease via immunogenetics. AB - The major inflammatory bowel diseases, Crohn's disease and ulcerative colitis, are both debilitating disorders of the gastrointestinal tract, characterized by a dysregulated immune response to unknown environmental triggers. Both disorders have an important and overlapping genetic component, and much progress has been made in the last 20 years at elucidating some of the specific factors contributing to disease pathogenesis. Here we review our growing understanding of the immunogenetics of inflammatory bowel disease, from the twin studies that first implicated a role for the genome in disease susceptibility to the latest genome-wide association studies that have identified hundreds of associated loci. We consider the insight this offers into the biological mechanisms of the inflammatory bowel diseases, such as autophagy, barrier defence and T-cell differentiation signalling. We reflect on these findings in the context of other immune-related disorders, both common and rare. These observations include links both obvious, such as to pediatric colitis, and more surprising, such as to leprosy. As a changing picture of the underlying genetic architecture emerges, we turn to future directions for the study of complex human diseases such as these, including the use of next generation sequencing technologies for the identification of rarer risk alleles, and potential approaches for narrowing down associated loci to casual variants. We consider the implications of this work for translation into clinical practice, for example via early therapeutic hypotheses arising from our improved understanding of the biology of inflammatory bowel disease. Finally, we present potential opportunities to better understand environmental risk factors, such as the human microbiota in the context of immunogenetics. PMID- 26257099 TI - Premedication with IV steroids effectively prevented anaphylactic reactions following ferumoxytol given as IV push in hematology and oncology patients. PMID- 26257100 TI - PDZ interaction of Vangl2 links PSD-95 and Prickle2 but plays only a limited role in the synaptic localisation of Vangl2. AB - Postsynaptic density-95/Discs large/Zonula occludens-1 (PDZ) domain-mediated protein interactions play pivotal roles in various molecular biological events, including protein localisation, assembly, and signal transduction. Although the vertebrate regulator of planar cell polarity Van Gogh-like 2 (Vangl2) was recently described as a postsynaptic molecule with a PDZ-binding motif, the role of its PDZ interaction at the synapse is unknown. In this report, we demonstrate that the PDZ interaction was dispensable for the normal cluster formation of Vangl2 and not absolutely required for the synapse-associated localisation of Vangl2 in cultured hippocampal neurons. We further showed that the synaptic localisation of Vangl2 was categorised into two types: overlapping co localisation with postsynaptic density (PSD)-95 or highly correlated but complementary pattern of association with PSD-95. Only the former was significantly sensitive to deletion of the PDZ-binding motif. In addition, the PDZ interaction enhanced the protein interactions between PSD-95 and Prickle2, which is another planar cell polarity factor that is localised at the postsynaptic density. Taken together with our recent report that the density of PSD-95 clusters was reduced in Vangl2-silenced neurons, these results suggest that Vangl2 determines the complex formation and clustering of postsynaptic molecules for synaptogenesis in mammalian brains. PMID- 26257101 TI - [Psycho-social factors involved in amputation. Systematic review of the literature]. PMID- 26257102 TI - Multiple conversion between the genes encoding bacterial class-I release factors. AB - Bacteria require two class-I release factors, RF1 and RF2, that recognize stop codons and promote peptide release from the ribosome. RF1 and RF2 were most likely established through gene duplication followed by altering their stop codon specificities in the common ancestor of extant bacteria. This scenario expects that the two RF gene families have taken independent evolutionary trajectories after the ancestral gene duplication event. However, we here report two independent cases of conversion between RF1 and RF2 genes (RF1-RF2 gene conversion), which were severely examined by procedures incorporating the maximum likelihood phylogenetic method. In both cases, RF1-RF2 gene conversion was predicted to occur in the region encoding nearly entire domain 3, of which functions are common between RF paralogues. Nevertheless, the 'direction' of gene conversion appeared to be opposite from one another-from RF2 gene to RF1 gene in one case, while from RF1 gene to RF2 gene in the other. The two cases of RF1-RF2 gene conversion prompt us to propose two novel aspects in the evolution of bacterial class-I release factors: (i) domain 3 is interchangeable between RF paralogues, and (ii) RF1-RF2 gene conversion have occurred frequently in bacterial genome evolution. PMID- 26257104 TI - Editorial: Early detection of mental health and neurodevelopmental disorders: the ethical challenges of a field in its infancy. AB - The signs of many mental health and neurodevelopmental conditions first appear in childhood and diagnosis can reliably be made by school age for most. Such conditions can be chronically disabling and confer significant long-term impairment. Determining early risk signs and first emerging symptoms of disorder is imperative to enhance early detection and to identify targets and ideal time points for prevention and intervention efforts. This Special Issue of JCPP focuses on the prospect of earlier identification of conditions that are traditionally diagnosed later in childhood. Ten invited empirical articles cover topics related to the science of early detection. Several are focused on prediction of later diagnosis, of functional impairment, and of future service utilization, while others cover instrument development and topics related to screening. The papers span the conditions of ADHD, ASD, dyslexia, mood dysregulation, disruptive behavior disorders, and anxiety disorders. This Editorial provides an overview of the invited contributions and the perspectives they provide on the ethical challenges and choices of a field still in its infancy. PMID- 26257103 TI - [Pomalidomide for multiple myeloma]. AB - Once characterized by a very poor outcome, multiple myeloma (MM) now has a significantly prolonged survival, with major improvements allowed by the use of "novel agents": proteasome inhibitors (first-in-class bortezomib) and immunomodulatory compounds (IMiDs; first-in-class thalidomide and lenalidomide). However, the vast majority - if not all - of patients with MM ultimately end up being refractory to all existing drugs, including these efficient novel agents. There is a clear unmet medical need in this situation, which warrants the development of the next generation of proteasome inhibitors and IMiDs, as well as new drug classes. This review focuses on pomalidomide, the next generation IMiD, recently approved by the US FDA and the EMA for patients with relapsed or refractory MM who have received at least two prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on their last therapy. PMID- 26257106 TI - The loss of fragile Y chromosomes (comment on 10.1002/bies.201500040). PMID- 26257105 TI - Infection Rate and Risk Factors in Patients Treated With Azacitidine. PMID- 26257107 TI - An Argument for Light Microscopy - A Review of Forensic Microscopy for Trace Evidence Analysis. AB - The microscope may seem to be a relic of an antiquated age of science when compared with some of today's advanced instrumentation. But microscopy can be as powerful as many current technologies and, in some cases, more powerful. The microscope is a nearly universal symbol of science, representing our ability to explore the world below the limits of our perception. Forensic science is equally well represented by the microscope. A brief review of some of the central concepts of microscopy is presented along with case reviews that show the utility of trace evidence. PMID- 26257108 TI - Examination, Analysis, and Application of Hair in Forensic Science - Animal Hair. AB - This article reviews the examination of animal hairs and their role in the forensic arena. The forensic examination of animal hair is a well-established discipline and has been so for two centuries. Examination is largely based on microscopy, which may enable the hair analyst to identify a hair as animal in origin, to characterize the hair to a particular species, and to conduct comparative examinations. Education and training underpin the ability of the hair analyst with the specialized knowledge and expertise required to proficiently conduct these examinations and give appropriate weight to the findings. This article will also discuss the effect two relative "newcomers" have exerted on the forensic examination of animal hair - (a) the transfer and persistence of animal hairs and (b) DNA profiling. Opinions regarding the transfer and persistence of animal hairs have been based on the data obtained from studies conducted on textile fibers because of the lack of data available for animal hairs. Preliminary studies conducted specifically on the transfer and persistence of animal hairs has shown that the results are comparable to the studies conducted on textile fibers. The progress in DNA profiling has seen this method being used with increasing frequency in the examination of animal hair. The results provide a degree of individualization that has not been possible with comparative microscopy. In conclusion, this review article will clearly demonstrate the role, value, and eclectic application of animal hair examination to forensic science. PMID- 26257109 TI - Forensic Fiber Examination and Analysis. AB - Fiber evidence suffers from the same misperception as many other types of trace evidence, that it is weak in its significance. Despite this pejorative perception, textiles make excellent evidence because of their presence in our daily lives and the variations they demonstrate. Fibers from the textiles in our and others' environments transfer from surface to surface and variously persist. Textile fibers are produced with specific raw materials, production methods, and postproduction alterations that create this variety. The distribution and use of the fibers add to their distinctive significance. The number of methods used in analysis helps to define and identify the fibers. Millions of color shades are possible in textiles and yet color analysis is not a universal technique in forensic laboratories. Transfer study after transfer study demonstrates the rarity of finding unrelated fibers at random that exhibit the same microscopic characteristics and optical properties. Examples from casework also demonstrate the usefulness of forensic textile fiber analysis in demonstrating probative associations in criminal investigations. Additional work needs to be done to fortify and support these conclusions and provide the verification necessary to remove the taint of "could have". PMID- 26257110 TI - Forensic Human Hair Examination and Comparison in the 21st Century. AB - Forensic hair examination and comparison is often undervalued as evidence. Significant information can be developed from a thorough microscopic examination and comparison of human and animal hairs that can assist criminal and civil investigations. Animal hairs can be distinguished easily from human hairs and often can be specified to a genus, species, or even breed. Human hairs often can be identified as to their body area origin and the racial ancestry of the person from whom they originated. Additionally, damage, disease, or cosmetic treatments can be identified and described. Finally, suitable hairs can be compared microscopically with known hair samples to determine if they could have come from the same source. This application is now being augmented by mitochondrial DNA analysis, which enhances the information already available from a microscopic examination of evidentiary hairs. Training and qualification of forensic hair examiners is crucial to the quality and reliability of forensic hair examinations. Many of the weaknesses in forensic hair examinations seen to date are a result of inadequate training of forensic hair examiners and a lack of understanding about the fundamental nature of the examination of hairs. Mitochondrial DNA offers a chance for the rehabilitation and validation of microscopical examination of human, and potentially animal, hairs. PMID- 26257111 TI - Genetic variability of ten Chinese indigenous goats using MHC-linked microsatellite markers. AB - In this study, the genetic variability of Chinese indigenous goat breeds (Capra hircus) was analyzed using the MHC-associated microsatellite markers BF1, BM1818, BM1258, and DYMS1. To examine genetic variability, the levels of heterozigosity, degrees of inbreeding, and genetic differences among the breeds were analyzed. The mean number of alleles ranged from 5.50+/-3.70 in Enshi black goats (EB) to 11.50+/-3.70 in the Jianyang big ear (JE) breed. The mean observed heterozygosity and mean expected heterozygosity varied from 0.25+/-0.04 in Jining Qing goats (JQ) to 0.54+/-0.05 in Chuannan black goats (CN) and from 0.49+/-0.18 in Hechuan white goats (HW) to 0.78+/-0.05 in JE, respectively. The mean FIS values ranged from 0.23 in HW to 0.51 in JQ. In addition, the genetic variation among populations and geographic location did indicate a correlation of genetic differences with geographic distance, which was revealed by the phylogenetic network. In conclusion, the high variability and population structure among Chinese native goats in the Major Histocompatibility Complex would be caused by co-evolution between MHC alleles and the epidemic history or pathogens in different agro-ecological zones. PMID- 26257112 TI - Real time observation of the excimer formation dynamics of a gas phase benzene dimer by picosecond pump-probe spectroscopy. AB - We observed the real-time excimer (EXC) formation dynamics of a gas phase benzene dimer (Bz2) cluster after photo-excitation to the S1 state by applying an ionization detected picosecond transient absorption method for probing the visible EXC absorption for the first time. The time evolution of the EXC absorption from the S1 0(0) level shows a rise that is well fitted by a single exponential function with a time constant of 18 +/- 2 ps. The structure of the Bz dimer has a T-shaped structure in the ground electronic state, and that in the EXC state is a parallel sandwich (SW) structure. Thus, the observed rise time corresponds to the structural change from the T to the SW structures, which directly shows the EXC formation. On the other hand, the EXC formation after excitation of the S1 6(1) vibrational level of the stem site showed a faster rise of the time constant of 10 +/- 2 ps. Supposing equilibrium between the EXC and the local excited states, it followed that the intramolecular vibrational energy redistribution rate of the 6(1) level is largely enhanced and becomes faster than the EXC formation reaction. PMID- 26257113 TI - Multiple paternity and hybridization in two smooth-hound sharks. AB - Multiple paternity appears to be a common trait of elasmobranch mating systems, with its occurrence likely driven by convenience, due to females seeking to minimize the stress of male harassment. Here we use molecular markers to analyse the frequency of multiple paternity in two related viviparous sharks, Mustelus mustelus and Mustelus punctulatus. We first applied molecular methods to assign pregnant females, embryos and additional reference adults (N = 792) to one of the two species. Paternity analysis was performed using a total of 9 polymorphic microsatellites on 19 females and 204 embryos of M. mustelus, and on 13 females and 303 embryos of M. punctulatus. Multiple paternity occurs in both species, with 47% of M. mustelus and 54% of M. punctulatus litters sired by at least two fathers. Female fecundity is not influenced by multiple mating and in 56% of polyandrous litters paternity is skewed, with one male siring most of the pups. Genetic analyses also revealed hybridization between the two species, with a M. punctulatus female bearing pups sired by a M. mustelus male. The frequency of polyandrous litters in these species is consistent with aspects of their reproductive biology, such as synchronous ovulation and possible occurrence of breeding aggregations. PMID- 26257114 TI - Central nervous system imaging findings of hemophagocytic syndrome. AB - We present a rare case of intracranial involvement in hemophagocytic lymphohistiocytosis (HLH) in an adult patient. MRI features in HLH may mimic those of other neoplastic, infectious, or inflammatory disorders. Key imaging findings correlate to central nervous system inflammation and include diffuse leptomeningeal enhancement, white matter changes with variable enhancement, hemorrhage, and restricted diffusion. Recognition of the imaging characteristic in correlation with clinical presentation, laboratory values, and biopsy findings is essential for making a correct diagnosis. PMID- 26257115 TI - Idiopathic fibrosing mediastinitis: spectrum of imaging findings with emphasis on its association with IgG4-related disease. AB - PURPOSE: The purpose of this study was to review the clinicoradiological features of idiopathic fibrosing mediastinitis (FM). METHODS: The records of six patients with idiopathic FM were retrospectively reviewed. RESULTS: The most common presenting symptom was cough. There were three localized forms and three diffuse forms. Definitive histological diagnosis was most commonly made with mediastinoscopy. Interestingly, three of our patients had disease manifestations of IgG4-related disease (IgG4-RD) outside the mediastinum. CONCLUSION: The imaging findings of idiopathic FM vary depending on the involved mediastinal structures. Therapeutic options include medical treatment, stenting, or surgery. Radiologists should pay attention to the possible association of idiopathic FM with extrathoracic manifestations of the IgG4-RD spectrum. PMID- 26257116 TI - Assessment of improvement scenario for water quality in Mogan Lake by using the AQUATOX Model. AB - In this study, the improvement scenarios for water quality in Mogan Lake were investigated using the AQUATOX Model. The ecosystem model AQUATOX simulates conventional pollutants, such as nutrients and sediments, and considers several trophic levels, including attached and planktonic algae, submerged aquatic vegetation, several types of invertebrates, and several types of fish. In this study, all data measured at both lakes and creeks was loaded into the AQUATOX Model including both initial concentration and dynamic loading for the year 2002. Then, the AQUATOX Model was calibrated and verified for the years 2004 and 2005. Accordingly, the Aquatox Model was utilized for the analysis of future scenarios as to improve water quality in terms of conventional parameters such as dissolved oxygen, temperature, total suspended solids, pH, total nitrogen, total phosphorus, and labile and refractory organic matters in water colon and sediment. During the development of future scenarios, some plans regarding measures were taken into account the modeling periods. In one of the scenarios, constructed wetlands located in big creeks' mouths were used for improving the water quality in Mogan Lake. The results indicated that Mogan Lake would improve its hypertrophic situation towards eutrophic situation. It would be anticipated that if the situation goes on like this, Mogan Lake would improve eutrophic situation towards mezotrophic situation. PMID- 26257117 TI - Photochemistry of tetra- through hexa-brominated dioxins/furans, hydroxylated and native BDEs in different media. AB - The aim of this study was to investigate (i) the behavior of native PBDEs during UV irradiation in different media, (ii) the possibility of their transformation into hydroxylated PBDEs in aqueous media, and (iii) the photochemistry/levels of brominated dioxins/furans formed from hydroxylated PBDEs. Debromination leading to the formation of a wide range of low-brominated congeners was the main path of photocatalyzed transformations of PBDEs. In organic solvents other than toluene, BDEs degraded in line with the pseudo first order kinetics (10-20 min half-life, depending on congener type and reaction medium). Irradiated BDE 209 congener behaved quite differently than lower-brominated BDEs: detectable amounts of various bromo-benzenes were found. That suggests that UV irradiation of BDE 209 leads to cleavage of the ether bound between the congener's aromatic rings. Formation of bromophenyl bromo-methyl-biphenyl ethers or benzyl bromophenoxybenzenes was observed in irradiated PBDE toluene-based solutions. The total concentration of OH-BDEs found in the reaction medium did not exceed 0.2% of the initial precursor mass. Moreover, lower-brominated congeners detected in the reaction medium indicate subsequent debromination of OH-BDEs or hydro debromination of the degraded congeners. Brominated dioxins and low levels of furans were observed in samples containing OH-BDEs. The total mass of dioxins did not exceed 3.5% of the initial precursor mass. PMID- 26257118 TI - Validation of cross-contamination control in biological safety cabinet for biotech/pharmaceutical manufacturing process. AB - For class II, type A2 biological safety cabinets (BSC), NSF/ANSI Standard 49 should be conformed in cabinet airflow velocity derivation, particle contamination, and aerodynamic flow properties. However, there exists a potential problem. It has been built that the cabinet air flow stabilize is influenced by the quantity of downflow of air and the height above the cabinet exhaust opening. Three air downflow quantities were compared as an operating apparatus was placed from 20 to 40 cm above the bench of the cabinet. The results show that the BSC air downflow velocity is a function of increased sampling height, displaying that containment is improvingly permitted over product protection as the sampling height decreases. This study investigated the concentration gradient of particles at various heights and downflow air quantity from the bench of the BSC. Experiment results indicate that performance near the bench was better than in the rest of the BSC. In terms of height, the best cleanliness was measured at a height of 10 cm over the bench; it reduced actually with add in height. The empirical curves accommodate, founded on the concentration gradient of particle created was elaborated for evaluating the particle concentration at different heights and downflow air quantity from the source of the bench of the BSC. The particle image velocimetry system applied for BSC airflow research to fix amount of airflow patterns and air distribution measurement and results of measurements show how obstructions can greatly influence the airflow and contaminant transportation in a BSC. PMID- 26257119 TI - Influence of effluent organic matter on copper speciation and bioavailability in rivers under strong urban pressure. AB - This study focuses on spatiotemporal variations in the type of dissolved organic matter (DOM) and copper binding ability both upstream and downstream of Paris. It also compares the relative influence of both natural DOM upstream of Paris and effluent dissolved organic matter (EfDOM) output from a wastewater treatment plant (WWTP) on trace metal speciation and bioavailability in aquatic systems. In addition to the typical high- and low-affinity binding sites, a third family of very high-affinity binding sites has been highlighted for EfDOM. In receiving waters downstream of Paris during low-flow periods, the percentage of high- and very high-affinity sites originating from EfDOM reaches nearly 60 %. According to the speciation computation, the free copper concentration upstream of Paris exceeds the downstream Paris concentration by a factor of 2 to 4. As regards copper bioavailability, the highest EC50tot values were observed for EfDOM and downstream DOM, with a very low aromaticity and low UV absorbance. This finding suggests that specific ultraviolet absorbance (SUVA) is unlikely to be useful in assessing metal speciation and toxicity in aquatic systems subject to strong urban pressures. These results also highlight that the copper speciation computation for surface water exposed to considerable human pressures should include not only the humic and/or fulvic part of dissolved organic carbon but more hydrophilic fractions as well, originating for example from EfDOM. PMID- 26257120 TI - Effects of freeze-thaw on characteristics of new KMP binder stabilized Zn- and Pb contaminated soils. AB - For viable and sustainable reuse of solidified/stabilized heavy metal contaminated soils as roadway subgrade materials, long-term durability of these soils should be ensured. A new binder, KMP, has been developed for solidifying/stabilizing soils contaminated with high concentrations of heavy metals. However, the effects of long-term extreme weather conditions including freeze and thaw on the leachability and strength of the KMP stabilized contaminated soils have not been investigated. This study presents a systematic investigation on the impacts of freeze-thaw cycle on leachability, strength, and microstructural characteristics of the KMP stabilized soils spiked with Zn and Pb individually and together. For comparison purpose, Portland cement is also tested as a conventional binder. Several series of tests are conducted including the toxicity characteristic leaching procedure (TCLP), modified European Community Bureau of Reference (BCR) sequential extraction procedure, unconfined compression test (UCT), and mercury intrusion porosimetry (MIP). The results demonstrate that the freeze-thaw cycles have much less impact on the leachability and strength of the KMP stabilized soils as compared to the PC stabilized soils. After the freeze thaw cycle tests, the KMP stabilized soils display much lower leachability, mass loss, and strength loss. These results are assessed based on the chemical speciation of Zn and Pb, and pore size distribution of the soils. Overall, this study demonstrates that the KMP stabilized heavy metal-contaminated soils perform well under the freeze-thaw conditions. PMID- 26257121 TI - Characteristics of particle-bound polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in atmosphere used in carbon black feeding process at a tire manufacturing plant. AB - Concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were estimated for different particle size distributions in a carbon black feeding process at a tire manufacturing plant on 15 days in March and April of 2014. A total of 75 integrated air samples were collected using a micro-orifice uniform deposition impactor (MOUDI). Particle-bound PCDD/Fs were analyzed using a high-resolution gas chromatograph/high-resolution mass spectrometer (HRGC/HRMS). Concentrations of thoracic particles and total particles produced in the carbon black feeding process of a tire manufacturing plant were measured in ranges of 0.19-2.61 and 0.28-4.22 mg/m(3), respectively. On all sampling days, the three most abundant species of PCDD/Fs were OCDD, 1,2,3,4,6,7,8-HpCDF, and OCDF. The mean concentrations of total PCDD/Fs were 0.74-6.83 pg/m(3) within five particle size ranges. Total I-TEQ in particulate matter (PM)<1.0 was 2.2 and 3.2 times higher than those in PM>18 and PM2.5-10, respectively. However, the total I-TEQ of thoracic PM contributed approximately 74 % of the total I-TEQ of total PM. The assessment of health risk indicates that exposure to fractions of thoracic PM by inhalation poses a significant cancer risk (>10(-6)). PMID- 26257122 TI - Mass Spectrometric Data of Commonly Abused Amphetamines and Their Derivatives - Cross Contribution of Ion Intensity between the Analytes and Their Isotopically Labeled Analogs. AB - With GC-MS as the preferred method and isotopically labeled analogs of the analytes as the internal standards (ISs) of choice for the analysis of drugs/metabolites in biological specimens, one important aspect associated with chemical derivatization (CD) is that the CD products derived from the analyte and the selected IS must generate ions suitable for designating the analyte and the IS; these ions cannot have significant crosscontribution (CC), i.e., contribution to the intensity of the ion designated for the analyte by the IS, and vice versa. With this in mind, the authors have reviewed literature and commercial information on common CD reagents and methods and conducted a thorough search of isotopically labeled analogs of commonly abused amphetamine-type drugs/metabolites that are commercially available. These ISs and analytes were then derivatized with various derivatization groups. These CD products were then analyzed by GC-MS and the resulting MS data are presented here in two forms: (a) systematic presentation of full-scan spectra; and (b) tabulation of CC data for ions with potential for designating the ISs and analytes. Many (if not most) of these full-scan spectra are not yet available in the literature and should be of daily reference value to forensic and clinical laboratories that are engaged in the analysis of these drugs/metabolites. Full-scan MS data were further used to select ion-pairs with potential for designating the analytes and ISs in quantitative analysis protocols. The CC data of these ion-pairs were evaluated using data collected under the SIM mode and summarized in table format. These data should save enormous amounts of time and efforts for practicing laboratories in their search for this analytical parameter. PMID- 26257123 TI - 1,25-Dihydroxy-vitamin D3 regulates NK-cell cytotoxicity, cytokine secretion, and degranulation in women with recurrent pregnancy losses. AB - Vitamin D has a pivotal role in regulating immune responses by promoting Th2 immune responses and suppressing Th1 responses. Propensities to a Th1 immune response and increased NK-cell levels and cytotoxicity have been reported in women with recurrent pregnancy losses (RPL). In women with RPL, vitamin D deficiency is prevalent; however, the effect of vitamin D on NK cells is largely unknown. In this study, we demonstrated that CD69(+) activating receptor expression on NK cells was significantly decreased by incubation with 1,25(OH)2 D3 in a dose-dependent manner, while CD158a and CD158b inhibitory receptor expression was upregulated. The degranulation marker CD107a was significantly downregulated on NK cells following incubation with 1,25(OH)2 D3 . NK-cell conjugation with K562 target cells was not affected by 1,25(OH)2 D3 ; however, depolarization of perforin granules in conjugated NK cells was significantly increased. TLR4 expression on NK cells was significantly decreased and TNF-alpha and IFN-gamma production was significantly reduced by 1,25(OH)2 D3 through interference with NF-kappaB. Our results suggest 1,25(OH)2 D3 has immune regulatory effects on NK cell cytotoxicity, cytokine secretion and degranulation process as well as TLR4 expression. Potential therapeutic application of 1,25(OH)2 D3 for dysregulated NK-cell immunity should be explored in the future. PMID- 26257124 TI - Simulation with quantum mechanics/molecular mechanics for drug discovery. AB - INTRODUCTION: Biological macromolecules, such as proteins or nucleic acids, are (still) molecules and thus they follow the same chemical rules that any simple molecule follows, even if their size generally renders accurate studies unhelpful. However, in the context of drug discovery, a detailed analysis of ligand association is required for understanding or predicting their interactions and hybrid quantum mechanics/molecular mechanics (QM/MM) computations are relevant tools to help elucidate this process. Areas covered: In this review, the authors explore the use of QM/MM for drug discovery. After a brief description of the molecular mechanics (MM) technique, the authors describe the subtractive and additive techniques for QM/MM computations. The authors then present several application cases in topics involved in drug discovery. Expert opinion: QM/MM have been widely employed during the last decades to study chemical processes such as enzyme-inhibitor interactions. However, despite the enthusiasm around this area, plain MM simulations may be more meaningful than QM/MM. To obtain reliable results, the authors suggest fixing several keystone parameters according to the underlying chemistry of each studied system. PMID- 26257125 TI - Sub-surface alloying largely influences graphene nucleation and growth over transition metal substrates. AB - Sub-surface alloying (SSA) can be an effective approach to tuning surface functionalities. Focusing on Rh(111) as a typical substrate for graphene nucleation, we show strong modulation by SSA atoms of both the energetics and kinetics of graphene nucleation simulated by first-principles calculations. Counter-intuitively, when the sub-surface atoms are replaced by more active solute metal elements to the left of Rh in the periodic table, such as the early transition metals (TMs), Ru and Tc, the binding between a C atom and the substrate is weakened and two C atoms favor dimerization. Alternatively, when the alloying elements are the late TMs to the right of Rh, such as the relatively inert Pd and Ag, the repulsion between the two C atoms is enhanced. Such distinct results can be well addressed by the delicately modulated activities of the surface host atoms in the framework of the d-band theory. More specifically, we establish a very simple selection rule for optimizing the metal substrate for high quality graphene growth: the introduction of an early (late) solute TM in the SSA lowers (raises) the d-band center and the activity of the top-most host metal atoms, weakening (strengthening) the C-substrate binding, meanwhile both energetically and kinetically facilitating (hindering) the graphene nucleation, and simultaneously promoting (suppressing) the orientation disordering the graphene domains. Importantly, our preliminary theoretical results also show that such a simple rule is also proposed to be operative for graphene growth on the widely invoked Cu(111) catalytic substrate. PMID- 26257126 TI - Withania somnifera aqueous extract facilitates the expression and release of GnRH: In vitro and in vivo study. AB - Ashwagandha (Withania somnifera) has a long history in traditional medicines as an aphrodisiac. It has been known to influence sexual behaviour in animal models but mechanism of action is still unknown. The present study was aimed to investigate the mechanisms by which Ashwagandha extract exert its gonadotropic activities. Due to the complexity of neuroendocrine pathways, there are limited in vitro models available despite the strong demand for such systems to study and predict neuroendocrine effects of chemicals or natural products. Immortalized rat hypothalamic GnV-3 cell line was investigated as a model to screen for neuroendocrine effects of Ashwagandha extract. GnV-3 cells were cultured under different media conditions and evaluated after treatment with Ashwagandha water extract, for GnRH expression and release by immunostaining and ELISA respectively. These cells acquired differentiated morphology, characteristic shape displayed by preoptic GnRH neurons in vivo. In addition, GnV-3 cells exhibited upregulation of plasticity related polysialylated neural cell adhesion molecule (PSA-NCAM) and mature dendrite marker microtubule associated protein (MAP2) as well as GnRH expression and release. Chloroform fraction of the extract proved to exhibit all the bioactive properties as it induced differentiation and upregulated GnRH and MAP2 expression in GnV-3 cells, similar to Ashwagandha extract. Withanone and Withaferin A were found to be present in ASH-WEX and chloroform fraction while Withanone came out to be the major constituent of chloroform fraction. The preliminary in vivo studies in adult male animals showed that ASH-WEX was able to upregulate the GnRH levels although non-significantly. Taken together, this data demonstrate significant morphological and physiological changes in GnV-3 cells after treatment with Ashwagandha extract and may suggest the potential beneficial effects of Ashwagandha on reproductive functions in vivo. PMID- 26257127 TI - The optical properties and quantum chemical calculations of thienyl and furyl derivatives of pyrene. AB - A detailed electrochemical, photophysical and theoretical study is presented for various new thienyl and furyl derivatives of pyrene. Their optical properties are described based on UV-VIS absorption and both steady-state and time-resolved fluorescence spectroscopy. DFT and TDDFT calculations are also presented to support experimental data. The calculations results show that HOMO-LUMO orbitals are delocalized uniformly between aromatic core and aryl substituents. Good electrochemical stability of thienyl and furyl hybrids of pyrene confirm their potential application for light emitting electrochemical cells or spintronics mainly due to their beneficial optical and charge transport properties in electrochromic devices. In order to demonstrate this potential, an OLED device is presented. Synthesized compounds included in this OLED device both facilitate electron transport and act as a light emitting layer. PMID- 26257128 TI - Controlled release of bioactive PDGF-AA from a hydrogel/nanoparticle composite. AB - Polymer excipients, such as low molar mass poly(ethylene glycol) (PEG), have shown contradictory effects on protein stability when co-encapsulated in polymeric nanoparticles. To gain further insight into these effects, platelet derived growth factor (PDGF-AA) was encapsulated in polymeric nanoparticles with vs. without PEG. PDGF-AA is a particularly compelling protein, as it has been demonstrated to promote cell survival and induce the oligodendrocyte differentiation of neural stem/progenitor cells (NSPCs) both in vitro and in vivo. Here we show, for the first time, the controlled release of bioactive PDGF AA from an injectable nanoparticle/hydrogel drug delivery system (DDS). PDGF-AA was encapsulated, with high efficiency, in poly(lactide-co-glycolide) nanoparticles, and its release from the drug delivery system was followed over 21 d. Interestingly, the co-encapsulation of low molecular weight poly(ethylene glycol) increased the PDGF-AA loading but, unexpectedly, accelerated the aggregation of PDGF-AA, resulting in reduced activity and detection by enzyme linked immunosorbent assay (ELISA). In the absence of PEG, released PDGF-AA remained bioactive as demonstrated with NSPC oligodendrocyte differentiation, similar to positive controls, and significantly different from untreated controls. This work presents a novel delivery method for differentiation factors, such as PDGF-AA, and provides insights into the contradictory effects reported in the literature of excipients, such as PEG, on the loading and release of proteins from polymeric nanoparticles. STATEMENT OF SIGNIFICANCE: Previously, the polymer poly(ethylene glycol) (PEG) has been used in many biomaterials applications, from surface coatings to the encapsulation of proteins. In this work, we demonstrate that, unexpectedly, low molecular weight PEG has a deleterious effect on the release of the encapsulated protein platelet-derived growth factor AA (PDGF-AA). We also demonstrate release of bioactive PDGF-AA (in the absence of PEG). Specifically, we demonstrate the differentiation of neural stem and progenitor cells to oligodendrocytes, similar to what is observed with the addition of fresh PDGFAA. A differentiated oligodendrocyte population is a key strategy in central nervous system regeneration. This work is the first demonstration of controlled PDGF-AA release, and also brings new insights to the broader field of protein encapsulation. PMID- 26257129 TI - The human gut microbiota and virome: Potential therapeutic implications. AB - Human gut microbiota is a complex ecosystem with several functions integrated in the host organism (metabolic, immune, nutrients absorption, etc.). Human microbiota is composed by bacteria, yeasts, fungi and, last but not least, viruses, whose composition has not been completely described. According to previous evidence on pathogenic viruses, the human gut harbours plant-derived viruses, giant viruses and, only recently, abundant bacteriophages. New metagenomic methods have allowed to reconstitute entire viral genomes from the genetic material spread in the human gut, opening new perspectives on the understanding of the gut virome composition, the importance of gut microbiome, and potential clinical applications. This review reports the latest evidence on human gut "virome" composition and its function, possible future therapeutic applications in human health in the context of the gut microbiota, and attempts to clarify the role of the gut "virome" in the larger microbial ecosystem. PMID- 26257130 TI - Study of the matrix effects of tetrodotoxin and its content in cooked seafood by liquid chromatography with triple quadrupole mass spectrometry. AB - Tetrodotoxin is a marine biotoxin with high acute toxicity. The levels in cooked seafood will help us to assess its intake in humans and may help assess the risk of toxicity. However, heavy matrices hinder the direct quantitation of tetrodotoxin. A quantitative method of measuring tetrodotoxin in cooked seafood using liquid chromatography with triple quadrupole mass spectrometry was established in this study. Tetrodotoxin was extracted from the sample matrix using 2% formic acid in methanol and cleaned using a cation exchange cartridge. The cleanup conditions were optimized. The matrix effects were determined using the postextraction spiking method and by comparing the slope of the linear regression equation in sample matrix to that in solvent. The limit of detection in the sample matrix was 5 MUg/kg and the limit of quantification was 10 MUg/kg. The mean recoveries at three spiking levels were 66.9-89.2% with relative standard deviations of 5.0-10.8% (n = 6) in five different matrices. Tetrodotoxin was found at concentrations of 26.1-2462 MUg/kg in nine of 83 cooked seafoods tested in this study. Eight analogs of Tetrodotoxin were detected in the samples studied. PMID- 26257131 TI - Resilience and Transitioning to Adulthood among Emerging Adults with Disabilities. AB - Transitioning to adulthood is not without challenges. The move away from family influence towards independence and self-determination is filled with uncertainty. Increased challenges and vulnerabilities in transitioning are evident among emerging adults with disabilities because they face additional challenges related to their disability over and above what others of this developmental stage experience. The purpose of this convergent parallel mixed methods study was to understand resilience in a select group of emerging adults with disabilities, who have been recognized for their accomplishments, as they are transitioning to adulthood. Quantitative instruments were used to measure the relationship among resilience, physical health, mental health, satisfaction with life, future orientation, and social support resources, while a qualitative focus group and individual interviews further explored the central phenomenon of resilience. This study revealed transitioning goals and values, challenges encountered while transitioning, and key attributes of resilience that have aided in transitioning. Findings conclude that resilience mitigates adversity and facilitates transitioning, the capacity for resilience is well within reach, and resilience comes from a variety of individual and environmental attributes. Nurses care for individuals and are uniquely present to intervene throughout all stages of the transitioning process. Knowing which resilient attributes are most effective in facilitating transitioning would be especially useful in the development of preventative holistic patient-centered nursing interventions. The research and practice implications of this study may suggest that resilience is a viable concept for the development of strength-based, patient-centered nursing interventions that facilitate transitioning. PMID- 26257132 TI - Food allergy in children with refractory gastroesophageal reflux disease. AB - BACKGROUND: Gastroesophageal reflux disease (GERD) and food allergy are frequent disorders of childhood. The purpose of this study was to determine the frequency of food allergy in children with refractory GERD. METHODS: A total of 151 children resistant to pharmacologic GERD treatment underwent skin prick test, specific immunoglobulin E, eosinophil count, atopy patch test (APT), and oral food challenge, and were then divided into three groups according to the results of oral milk challenge and allergy work-up: group A1, positive oral milk challenge and positive IgE-mediated allergy test; group A2, positive milk challenge and negative IgE-mediated allergy test; and group B, negative oral milk challenge and negative allergy tests. RESULTS: There were 35, 30 and 86 patients in group A1, group A2 and group B, respectively. A total of 28 of 35 patients in group A1 had cow's milk allergy and the other seven patients had egg allergy. APT positivity was more common in group A2. Endoscopic esophagitis was observed in six group A1 patients and in four group A2 patients. Bloody stools, atopic dermatitis and recurrent wheezing episodes were significantly more common in group A1 than in group A2 and group B (P < 0.001, for both). CONCLUSION: Cow's milk allergy was observed frequently in children resistant to pharmacologic GERD treatment. Combined skin prick and specific IgE tests, APT and oral food challenge is essential for avoidance of unnecessary elimination diet. PMID- 26257133 TI - Facile Synthesis of Gd-Cu-In-S/ZnS Bimodal Quantum Dots with Optimized Properties for Tumor Targeted Fluorescence/MR In Vivo Imaging. AB - Dual-modal imaging techniques have gained intense attention for their potential role in the dawning era of tumor early accurate diagnosis. Chelate-free robust dual-modal imaging nanoprobes with high efficiency and low toxicity are of essential importance for tumor targeted dual-modal in vivo imaging. It is still a crucial issue to endow Cd-free dual-modal nanoprobes with bright fluorescence as well as high relaxivity. Herein, a facile synthetic strategy was developed to prepare Gd-doped CuInS/ZnS bimodal quantum dots (GCIS/ZnS, BQDs) with optimized properties. The fluorescent properties of the GCIS/ZnS BQDs can be thoroughly optimized by varying reaction temperature, aging time, and ZnS coating. The amount of Gd precursor can be well-controlled to realize the optimized balance between the MR relaxivity and optical properties. The obtained hydrophobic GCIS/ZnS BQDs were surface engineered into aqueous phase with PEGylated dextran stearyl acid polymeric lipid vesicles (PEG-DS PLVs). Upon the phase transfer, the hydrophilic GCIS/ZnS@PLVs exhibited pronounced near-infrared fluorescence as well as high longitudinal relaxivity (r1 = 9.45 mM(-1) S(-1)) in water with good colloidal stability. In vivo tumor-bearing animal experiments further verified GCIS/ZnS@PLVs could achieve tumor-targeted MR/fluorescence dual-modal imaging. No toxicity was observed in the in vivo and ex vivo experiments. The GCIS/ZnS@PLVs present great potential as bimodal imaging contrast agents for tumor diagnosis. PMID- 26257134 TI - Identification of mutations, genotype-phenotype correlation and prenatal diagnosis of maple syrup urine disease in Indian patients. AB - Maple syrup urine disease (MSUD) is caused by mutations in genes BCKDHA, BCKDHB, DBT encoding E1alpha, E1beta, and E2 subunits of enzyme complex, branched-chain alpha-ketoacid dehydrogenase (BCKDH). BCKDH participates in catabolism of branched-chain amino acids (BCAAs) - leucine, isoleucine and valine in the energy production pathway. Deficiency or defect in the enzyme complex causes accumulation of BCAAs and keto-acids leading to toxicity. Twenty-four patients with MSUD were enrolled in the study for molecular characterization and genotype phenotype correlation. Molecular studies were carried out by sequencing of the 3 genes by Sanger method. Bioinformatics tools were employed to classify novel variations into pathogenic or benign. The predicted effects of novel changes on protein structure were elucidated by 3D modeling. Mutations were detected in 22 of 24 patients (11, 7 and 4 in BCKDHB, BCKDHA and DBT genes, respectively). Twenty mutations including 11 novel mutations were identified. Protein modeling in novel mutations showed alteration of structure and function of these subunits. Mutations, c.1065 delT (BCKDHB gene) and c.939G > C (DBT gene) were noted to be recurrent, identified in 6 of 22 alleles and 5 of 8 alleles, respectively. Two third patients were of neonatal classical phenotype (16 of 24). BCKDHB gene mutations were present in 10 of these 16 patients. Prenatal diagnoses were performed in 4 families. Consanguinity was noted in 37.5% families. Although no obvious genotype-phenotype correlation could be found in our study, most cases with mutation in BCKDHB gene presented in neonatal period. Large number of novel mutations underlines the heterogeneity and distinctness of gene pool from India. PMID- 26257135 TI - Vortex-assisted liquid-liquid microextraction using a low-toxicity solvent for the determination of five organophosphorus pesticides in water samples by high performance liquid chromatography. AB - Vortex-assisted liquid-liquid microextraction followed by high-performance liquid chromatography with UV detection was applied to determine Isocarbophos, Parathion methyl, Triazophos, Phoxim and Chlorpyrifos-methyl in water samples. 1 Bromobutane was used as the extraction solvent, which has a higher density than water and low toxicity. Centrifugation and disperser solvent were not required in this microextraction procedure. The optimum extraction conditions for 15 mL water sample were: pH of the sample solution, 5; volume of the extraction solvent, 80 MUL; vortex time, 2 min; salt addition, 0.5 g. Under the optimum conditions, enrichment factors ranging from 196 to 237 and limits of detection below 0.38 MUg/L were obtained for the determination of target pesticides in water. Good linearities (r > 0.9992) were obtained within the range of 1-500 MUg/L for all the compounds. The relative standard deviations were in the range of 1.62-2.86% and the recoveries of spiked samples ranged from 89.80 to 104.20%. The whole proposed methodology is simple, rapid, sensitive and environmentally friendly for determining traces of organophosphorus pesticides in the water samples. PMID- 26257136 TI - Association of Preoperative Anemia With Complications and Mortality Following Total Joint Arthroplasty. PMID- 26257137 TI - Mesenchymal Stem Cell Transplantation Promotes Neurogenesis and Ameliorates Autism Related Behaviors in BTBR Mice. AB - Autism spectrum disorders (ASD) are characterized by social communication deficits, cognitive rigidity, and repetitive stereotyped behaviors. Mesenchymal stem cells (MSC) have a paracrine regenerative effect, and were speculated to be a potential therapy for ASD. The BTBR inbred mouse strain is a commonly used model of ASD as it demonstrates robust behavioral deficits consistent with the diagnostic criteria for ASD. BTBR mice also exhibit decreased brain-derived neurotrophic factor (BDNF) signaling and reduced hippocampal neurogenesis. In the current study, we evaluated the behavioral and molecular effects of intracerebroventricular MSC transplantation in BTBR mice. Transplantation of MSC resulted in a reduction of stereotypical behaviors, a decrease in cognitive rigidity and an improvement in social behavior. Tissue analysis revealed elevated BDNF protein levels in the hippocampus accompanied by increased hippocampal neurogenesis in the MSC-transplanted mice compared with sham treated mice. This might indicate a possible mechanism underpinning the behavioral improvement. Our study suggests a novel therapeutic approach which may be translatable to ASD patients in the future. PMID- 26257138 TI - The 15q13.3 deletion syndrome: Deficient alpha(7)-containing nicotinic acetylcholine receptor-mediated neurotransmission in the pathogenesis of neurodevelopmental disorders. AB - Array comparative genomic hybridization (array CGH) has led to the identification of microdeletions of the proximal region of chromosome 15q between breakpoints (BP) 3 or BP4 and BP5 encompassing CHRNA7, the gene encoding the alpha7-nicotinic acetylcholine receptor (alpha7nAChR) subunit. Phenotypic manifestations of persons with these microdeletions are variable and some heterozygous carriers are seemingly unaffected, consistent with their variable expressivity and incomplete penetrance. Nonetheless, the 15q13.3 deletion syndrome is associated with several neuropsychiatric disorders, including idiopathic generalized epilepsy, intellectual disability, autism spectrum disorders (ASDs) and schizophrenia. Haploinsufficient expression of CHRNA7 in this syndrome has highlighted important roles the alpha7nAChR plays in the developing brain and normal processes of attention, cognition, memory and behavior throughout life. Importantly, the existence of the 15q13.3 deletion syndrome contributes to an emerging literature supporting clinical trials therapeutically targeting the alpha7nAChR in disorders such as ASDs and schizophrenia, including the larger population of patients with no evidence of haploinsufficient expression of CHRNA7. Translational clinical trials will be facilitated by the existence of positive allosteric modulators (PAMs) of the alpha7nAChR that act at sites on the receptor distinct from the orthosteric site that binds acetylcholine and choline, the receptor's endogenous ligands. PAMs lack intrinsic efficacy by themselves, but act where and when the endogenous ligands are released in response to relevant social and cognitive provocations to increase the likelihood they will result in alpha7nAChR ion channel activation. PMID- 26257139 TI - Chitosan based nanoparticles functionalized with peptidomimetic derivatives for oral drug delivery. AB - The goal of this study was to develop an optimized drug delivery carrier for oral mucosa applications able to release in situ bioactive molecules by using biopolymeric materials. Among them chitosan and poly(lactic-co-glycolic acid) (PLGA) have gained considerable attention as biocompatible carriers able to improve the delivery of active agents. The formulation of such vehicles in the form of nanoparticles (NPs) could permit to exploit the peculiar properties of nanomaterials in order to enhance the efficacy of active agents. Chitosan (CS) and PLGA chlorexidine dihydrochloride (CHX)-loaded NPs were synthesized by ionotropic gelation and osmosis based methodology respectively. In order to facilitate NPs adhesion on human dental surfaces, two different strategies were employed: PLGA particles with an external shell of CS to produce a positive surface charge allowing CHX loaded PLGA NPs to interact with the negative charged dental surfaces, while CS particles were functionalized with peptidomimetic derivative glutathione (GSH). The morphology was investigated by scanning electron microscopy. A sustained release profile of CHX from CS NPs was achieved. CS-based NPs adhered on human tooth surfaces in a simulated brushing and rinsing process and their in vitro toxicity evaluation on Human Gingival Fibroblasts (HGFs) was between 20 and 60% in all experimental conditions. Thanks to their adhesion properties and low cytotoxicity, the synthesized CS-based formulations may be efficiently exploited for therapy purposes or to enhance in vivo dental care (i.e. preparation of toothpastes or other cosmetics for daily oral care). PMID- 26257140 TI - Fluxes in PHA-storing microbial communities during enrichment and biopolymer accumulation processes. AB - The use of mixed microbial cultures for the production of polyhydroxyalkanoates (PHAs) is emerging as a viable technology. In this study, 16S rRNA gene amplicon pyrosequencing was used to analyse fluctuations in populations over a 63-day period within a PHA-storing mixed microbial community enriched on fermented whey permeate. This community was dominated by the genera Flavisolibacter and Zoogloea as well as an unidentified organism belonging to the phylum Bacteroidetes. The population was observed to cycle through an increase in Zoogloea followed by a return to a community composition similar to the initial one (highly enriched in Flavisolibacter). It was found that the PHA accumulation capacity of the community was robust to population flux during enrichment and even PHA accumulation, with final polymer composition dependent on the overall proportion of acetic to propionic acids in the feed. This community adaptation suggests that mixed culture PHA production is a robust process. PMID- 26257142 TI - Body fat distribution and its associated factors in Korean women with polycystic ovary syndrome. AB - AIM: To investigate the body fat distribution in Korean women with polycystic ovary syndrome (PCOS) and the association of those distribution with metabolic parameters and hormone profiles. METHODS: A total 90 patients with PCOS and 97 women without PCOS (control group) were included in this study. Total body fat, abdominal visceral fat, and subcutaneous fat were determined on abdominal fat computed tomography. Lipid profiles and sex-hormone binding globulin (SHBG), testosterone, free androgen index (FAI), and cortisol were measured in PCOS group. RESULTS: Total body fat and body fat distribution in the PCOS group were not significantly different from the control group in Korean women (P = 0.054, P = 0.761, P = 0.104), but abdominal visceral to subcutaneous fat ratio was larger in the PCOS group than the control group (P = 0.047). Not only total body fat and visceral fat, but also subcutaneous fat in the PCOS group had a positive correlation with homeostatic model assessment-insulin resistance, fasting blood sugar, low-density lipoprotein cholesterol, triglyceride, systolic blood pressure, diastolic blood pressure, fasting insulin, free testosterone, FAI, body mass index, but negative correlation with SHBG and high-density lipoprotein cholesterol. CONCLUSIONS: Korean PCOS women had the same body fat distribution as the control group. Subcutaneous fat was also correlated with metabolic parameters and hormone profiles in the Korean PCOS group. PMID- 26257144 TI - Attention is necessary for subliminal instrumental conditioning. AB - The capacity of humans and other animals to provide appropriate responses to stimuli anticipating motivationally significant events is exemplified by instrumental conditioning. Interestingly, in humans instrumental conditioning can occur also for subliminal outcome-predicting stimuli. However, it remains unclear whether attention is necessary for subliminal instrumental conditioning to take place. In two experiments, human participants had to learn to collect rewards (monetary gains) while avoiding punishments (monetary losses), on the basis of subliminal outcome-predicting cues. We found that instrumental conditioning can proceed subconsciously only if spatial attention is aligned with the subliminal cue. Conversely, if spatial attention is briefly diverted from the subliminal cue, then instrumental conditioning is blocked. In humans, attention but not awareness is therefore mandatory for instrumental conditioning, thus revealing a dissociation between awareness and attention in the control of motivated behavior. PMID- 26257143 TI - Controlled vaporized cannabis, with and without alcohol: subjective effects and oral fluid-blood cannabinoid relationships. AB - Vaporized cannabis and concurrent cannabis and alcohol intake are commonplace. We evaluated the subjective effects of cannabis, with and without alcohol, relative to blood and oral fluid (OF, advantageous for cannabis exposure screening) cannabinoid concentrations and OF/blood and OF/plasma vaporized-cannabinoid relationships. Healthy adult occasional-to-moderate cannabis smokers received a vaporized placebo or active cannabis (2.9% and 6.7% Delta(9) tetrahydrocannabinol, THC) with or without oral low-dose alcohol (~0.065g/210L peak breath alcohol concentration [BrAC]) in a within-subjects design. Blood and OF were collected up to 8.3 h post-dose and subjective effects measured at matched time points with visual-analogue scales and 5-point Likert scales. Linear mixed models evaluated subjective effects by THC concentration, BrAC, and interactions. Effects by time point were evaluated by dose-wise analysis of variance (ANOVA). OF versus blood or plasma cannabinoid ratios and correlations were evaluated in paired-positive specimens. Nineteen participants (13 men) completed the study. Blood THC concentration or BrAC significantly associated with subjective effects including 'high', while OF contamination prevented significant OF concentration associations <1.4 h post-dose. Subjective effects persisted through 3.3-4.3 h, with alcohol potentiating the duration of the cannabis effects. Effect-versus-THC concentration and effect-versus-alcohol concentration hystereses were counterclockwise and clockwise, respectively. OF/blood and OF/plasma THC significantly correlated (all Spearman r>=0.71), but variability was high. Vaporized cannabis subjective effects were similar to those previously reported after smoking, with duration extended by concurrent alcohol. Cannabis intake was identified by OF testing, but OF concentration variability limited interpretation. Blood THC concentrations were more consistent across subjects and more accurate at predicting cannabis' subjective effects. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26257141 TI - 4D flow cardiovascular magnetic resonance consensus statement. AB - Pulsatile blood flow through the cavities of the heart and great vessels is time varying and multidirectional. Access to all regions, phases and directions of cardiovascular flows has formerly been limited. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) has enabled more comprehensive access to such flows, with typical spatial resolution of 1.5*1.5*1.5 - 3*3*3 mm(3), typical temporal resolution of 30-40 ms, and acquisition times in the order of 5 to 25 min. This consensus paper is the work of physicists, physicians and biomedical engineers, active in the development and implementation of 4D Flow CMR, who have repeatedly met to share experience and ideas. The paper aims to assist understanding of acquisition and analysis methods, and their potential clinical applications with a focus on the heart and greater vessels. We describe that 4D Flow CMR can be clinically advantageous because placement of a single acquisition volume is straightforward and enables flow through any plane across it to be calculated retrospectively and with good accuracy. We also specify research and development goals that have yet to be satisfactorily achieved. Derived flow parameters, generally needing further development or validation for clinical use, include measurements of wall shear stress, pressure difference, turbulent kinetic energy, and intracardiac flow components. The dependence of measurement accuracy on acquisition parameters is considered, as are the uses of different visualization strategies for appropriate representation of time-varying multidirectional flow fields. Finally, we offer suggestions for more consistent, user-friendly implementation of 4D Flow CMR acquisition and data handling with a view to multicenter studies and more widespread adoption of the approach in routine clinical investigations. PMID- 26257145 TI - Mapping of post-translational modifications of spermatid-specific linker histone H1-like protein, HILS1. AB - In mammalian spermiogenesis, haploid round spermatids undergo dramatic biochemical and morphological changes and transform into motile mature spermatozoa. A majority of the histones are replaced by transition proteins during mid-spermiogenesis and later replaced by protamines, which occupy the sperm chromatin. In mammals, 11 linker histone H1 subtypes have been reported. Among them, H1t, HILS1, and H1T2 are uniquely expressed in testis, with the expression of HILS1 and H1T2 restricted to spermiogenesis. However, there is a lack of knowledge about linker histone role in the nuclear reorganization during mammalian spermiogenesis. Here, we report a method for separation of endogenous HILS1 protein from other rat testis linker histones by reversed-phase high performance liquid chromatography (RP-HPLC) and identification of 15 novel post translational modifications of HILS1, which include lysine acetylation and serine/threonine/tyrosine phosphorylation sites. Immunofluorescence studies demonstrate the presence of linker histone HILS1 and HILS1Y78p during different steps of spermiogenesis from early elongating to condensing spermatids. PMID- 26257146 TI - Sitting time and physical activity after stroke: physical ability is only part of the story. AB - BACKGROUND: Understanding factors that influence the amount of time people with stroke spend sitting and being active is important to inform the development of targeted interventions. OBJECTIVE: To explore the physical, cognitive, and psychosocial factors associated with daily sitting time and physical activity in people with stroke. METHOD: Secondary analysis of an observational study (n = 50, mean age 67.2 +/- 11.6 years, 33 men) of adults at least 6 months post-stroke. Activity monitor data were collected via a 7-day, continuous wear (24 hours/day) protocol. Sitting time [total, and prolonged (time in bouts of >= 30 minutes)] was measured with an activPAL3 activity monitor. A hip-worn Actigraph GT3X+ accelerometer was used to measure moderate-to-vigorous-intensity physical activity (MVPA) time. Univariate analyses examined relationships of stroke severity (National Institutes of Health Stroke Scale), physical [walking speed, Stroke Impact Scale (SIS) physical domain score], cognitive (Montreal Cognitive Assessment), and psychosocial factors (living arrangement, SIS emotional domain score) with sitting time, prolonged sitting time, and MVPA. RESULTS: Self reported physical function and walking speed were negatively associated with total sitting time (r = - 0.354, P = 0.022 and r = - 0.361, P = 0.011, respectively) and prolonged sitting time (r = - 0.5, P = 0.001 and - 0.45, P = 0.001, respectively), and positively associated with MVPA (r = 0.469, P = 0.002 and 0.431, P = 0.003, respectively). CONCLUSIONS: Physical factors, such as walking ability, may influence sitting and activity time in people with stroke, yet much of the variance in daily sitting time remains unexplained. Large prospective studies are required to understand the drivers of activity and sitting time. PMID- 26257148 TI - Reply: To PMID 25747676. PMID- 26257147 TI - Neuroprogression and Cognitive Functioning in Bipolar Disorder: A Systematic Review. AB - Bipolar disorder (BD) has been associated with impairments in a range of cognitive domains including attention, verbal learning, and mental flexibility. These deficits are increased during the acute phases of the illness and worsen over the course of BD. This review will examine the literature in relation to potential mechanisms associated with cognitive decline in BD. Scopus (all databases), Pubmed, and Ovid Medline were systematically searched with no language or year restrictions, up to January 2015, for human studies that collected cross-sectional and longitudinal cognitive data in adults with BD and matched healthy controls (HC). Selected search terms were "bipolar," "cognitive," "aging," "illness duration," "onset," and "progression." Thirty-nine studies satisfied the criteria for consideration. There is evidence that cognitive function in BD is negatively associated with features of illness progression such as number of mood episodes, illness duration, and hospitalizations. Aging does not appear to affect cognitive functioning to a greater extent than in HC. Furthermore, the small number of longitudinal studies in this field does not allow to reaching firm conclusion in terms of which sub-populations would be more prone to cognitive decline in BD. The decline in cognitive abilities over the course of the BD seems to be associated with the number of episodes and number of hospitalizations. No meaningful interaction of age and bipolar disorder has been found in terms of cognitive decline. Future large-scale longitudinal studies are necessary to confirm these findings and assist in the development of preventive interventions in vulnerable individuals. PMID- 26257149 TI - Concanavalin A immobilized magnetic poly(glycidyl methacrylate) beads for prostate specific antigen binding. AB - The aim of this study was to prepare Concanavalin A (Con A) immobilized magnetic poly(glycidyl methacrylate) (mPGMA) beads for prostate specific antigen (PSA) binding and to study binding capacities of the beads using lectin-glycoprotein interactions. Firstly, iron oxide nanoparticles were synthesized by co precipitation method and then, beads were synthesized by dispersion polymerization in the presence of iron oxide nanoparticles. Con A molecules were both covalently immobilized onto the beads directly and through the spacer arm (1,6-diaminohexane-HDMA). The total PSA and free PSA binding onto the mPGMA-HDMA Con A beads were higher than that of the mPGMA-Con A beads. Maximum PSA binding capacity was observed as 91.2 ng/g. Approximately 45% of the bound PSA was eluted by using 0.1 M mannose as elution agent. The mPGMA-HDMA-Con A beads could be reused without a remarkable decrease in the binding capacities after 5 binding desorption cycles. Serum fractions were analyzed using SDS-PAGE. The mPGMA-HDMA Con A beads could be useful for the detection of PSA and suggested as a model system for other glycoprotein biomarkers. PMID- 26257150 TI - DBS in Dystonia and Other Hyperkinetic Movement Disorders. AB - OPINION STATEMENT: The diagnosis and appropriate treatment of hyperkinetic movement disorders require a work up of potentially reversible metabolic, infectious and structural disorders as well as side effects of current medication. In pharmacoresistant movement disorders with a disabling impact on quality of life, deep brain stimulation (DBS) should be considered. At different targets, DBS has become an established therapy for Parkinson's disease (GPi-STN), tremor (VIM) and primary dystonia (GPi) with reasonable perioperative risks and side effects, established guidelines and some clinical and radiological predictive factors. In contrast, for other hyperkinetic movement disorders, including secondary dystonia, Gilles de la Tourette, chorea and ballism, only few data are available. Definite targets are not well defined, and reported results are of less magnitude than those of the recognized indications. In this expanding therapeutical field without worked out recommendations, an individual approach is needed with DBS indication assessment only after rigorous multidisciplinary scrutiny, restricted to expert centres. PMID- 26257151 TI - Concurrent Validity of the Defense and Veterans Pain Rating Scale in VA Outpatients. AB - OBJECTIVE: The purpose of this report is to investigate the concurrent validity of the Defense and Veterans Pain Rating Scale (DVPRS) with other validated self report measures in U.S. veterans. DESIGN: This correlational study was conducted using two samples of outpatients at the Washington, DC Veterans Affairs Medical Center who completed self-report measures relevant to pain conditions, including pain disability, quality of life, and mental health. Study 1 and 2 consisted of n = 204 and n = 13 participants, respectively. METHODS: Bivariate Spearman correlations were calculated to examine the correlation among total scores and subscale scores for each scale of interest. Multiple linear regressions were also computed in Study 1. RESULTS: In Study 1, the DVPRS interference scale (DVPRS-II) was significantly correlated with the Pain Disability Questionnaire (PDQ) (rho = 0.69, P < 0.001) and the Veterans RAND 36-item Health Survey physical and mental component scales (rho = -0.37, P < 0.001; rho = -0.46, P < 0.001, respectively). When controlling for sex, age, and other self-report measures, the relationship between the DVPRS-II and PDQ remained significant. In Study 2, pain interference on the DVPRS and Brief Pain Inventory were highly correlated (rho = 0.90, P < 0.001); however, the intensity scale of each measure was also highly associated with the interference summary scores. CONCLUSIONS: These findings provide preliminary evidence for the concurrent validity of the DVPRS as a brief, multidimensional measure of pain interference that make it a practical tool for use in primary care settings to assess the impact of pain on daily functioning and monitor chronic pain over time. PMID- 26257153 TI - Characterisation of dendritic cell subsets in chronically inflamed human epididymis. AB - Infection and inflammation of the genital tract are thought to be a primary aetiological factor of male infertility. Chronic epididymitis appears to be more important than prostatitis or seminal vesiculitis due to the direct interaction between sperm cells and epididymal epithelium. Dendritic cells (DCs) are a heterogeneous population of antigen-presenting cells that play a crucial role in the regulation of the immune response and immunological tolerance. The aim of this study was to investigate the expression and characteristic of different DC subsets in chronic inflammation of human epididymis and controls. Our study demonstrated that normal human epididymis contained only immature CD1a(+) DCs, CD11c(+) myeloid DCs (mDCs) and CD209(+) DCs whereas CD123(+) plasmacytoid DCs and CD83(+) mature DCs were virtually absent. The number of both CD11c(+) IL 23(+) mDCs and CD123(+) pDCs were significantly elevated in inflamed epididymis; meanwhile the mDC populations of CD1a(+), CD209(+) immature DCs and CD83(+) mature DCs also increased in inflamed group. Moreover, Th17 (CD4(+) IL-17(+)) cells were predominantly distributed under chronic inflammation of human epididymis. Taken together these results suggest that epididymal DCs might play a pivotal role in the development of chronic epididymitis and induce an increased recruitment of Th17 cells under inflammatory conditions. PMID- 26257152 TI - Ikarisoside A inhibits acetylcholine-induced catecholamine secretion and synthesis by suppressing nicotinic acetylcholine receptor-ion channels in cultured bovine adrenal medullary cells. AB - Ikarisoside A is a natural flavonol glycoside derived from plants of the genus Epimedium, which have been used in Traditional Chinese Medicine as tonics, antirheumatics, and aphrodisiacs. Here, we report the effects of ikarisoside A and three other flavonol glycosides on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. We found that ikarisoside A (1-100 MUM), but not icariin, epimedin C, or epimedoside A, concentration-dependently inhibited the secretion of catecholamines induced by acetylcholine, a physiological secretagogue and agonist of nicotinic acetylcholine receptors. Ikarisoside A had little effect on catecholamine secretion induced by veratridine and 56 mM K(+). Ikarisoside A (1-100 MUM) also inhibited (22)Na(+) influx and (45)Ca(2+) influx induced by acetylcholine in a concentration-dependent manner similar to that of catecholamine secretion. In Xenopus oocytes expressing alpha3beta4 nicotinic acetylcholine receptors, ikarisoside A (0.1-100 MUM) directly inhibited the current evoked by acetylcholine. It also suppressed (14)C catecholamine synthesis and tyrosine hydroxylase activity induced by acetylcholine at 1-100 MUM and 10-100 MUM, respectively. The present findings suggest that ikarisoside A inhibits acetylcholine-induced catecholamine secretion and synthesis by suppression of nicotinic acetylcholine receptor-ion channels in bovine adrenal medullary cells. PMID- 26257154 TI - Patient-related risk factors for urinary retention following ambulatory general surgery: a systematic review and meta-analysis. AB - BACKGROUND: Postoperative urinary retention (POUR) is a source of avoidable patient harm. The aim of this review is to identify and quantify the role of patient-related risk factors in the development of POUR following ambulatory general surgery. METHODS: Studies published until December 2014 were identified by searching MEDLINE, EMBASE, and PsycINFO databases. Risk factors assessed in 3 or more studies were meta-analyzed. RESULTS: Twenty-one studies were suitable for inclusion consisting of 7,802 patients. The incidence of POUR was 14%. Increased age and the presence of lower urinary tract symptoms significantly increased risk with odds ratios [ORs] of 2.11 (95% confidence interval [CI] 1.15 to 3.86) and 2.83 (1.57 to 5.08), respectively. Male sex was not associated with developing POUR (OR .96, 95% CI .62 to 1.50). Preoperative alpha-blocker use significantly decreased the incidence of POUR with an OR of .37 (95% CI .15 to .91). CONCLUSIONS: Increased age and the presence of lower urinary tract symptoms increase the risk of POUR, while alpha-blocker use confers protection. Male sex was not associated with POUR. These findings assist in preoperative identification of patients at high risk of POUR. PMID- 26257155 TI - Volume and methodological quality of randomized controlled trials in laparoscopic surgery: assessment over a 10-year period. AB - BACKGROUND: Measures have been taken to improve methodological quality of randomized controlled trials (RCTs). This review systematically assessed the trends in volume and methodological quality of RCTs on minimally invasive surgery within a 10-year period. DATA SOURCES: RCTs on minimally invasive surgery were searched in the 10 most cited general surgical journals and the 5 most cited journals of laparoscopic interest for the years 2002 and 2012. Bibliometric and methodological quality components were abstracted using the Scottish Intercollegiate Guidelines Network. The pooled number of RCTs from low contribution regions demonstrated an increasing proportion of the total published RCTs, compensating for a concomitant decrease of the respective contributions from Europe and North America. International collaborations were more frequent in 2012. Acceptable or high quality RCTs accounted for 37.9% and 54.4% of RCTs published in 2002 and 2012, respectively. Components of external validity were poorly reported. CONCLUSIONS: Both the volume and the reporting quality of laparoscopic RCTs have increased from 2002 to 2012, but there seems to be ample room for improvement of methodological quality. PMID- 26257156 TI - Extant-only comparative methods fail to recover the disparity preserved in the bird fossil record. AB - Most extant species are in clades with poor fossil records, and recent studies of comparative methods show they have low power to infer even highly simplified models of trait evolution without fossil data. Birds are a well-studied radiation, yet their early evolutionary patterns are still contentious. The fossil record suggests that birds underwent a rapid ecological radiation after the end-Cretaceous mass extinction, and several smaller, subsequent radiations. This hypothesized series of repeated radiations from fossil data is difficult to test using extant data alone. By uniting morphological and phylogenetic data on 604 extant genera of birds with morphological data on 58 species of extinct birds from 50 million years ago, the "halfway point" of avian evolution, I have been able to test how well extant-only methods predict the diversity of fossil forms. All extant-only methods underestimate the disparity, although the ratio of within to between-clade disparity does suggest high early rates. The failure of standard models to predict high early disparity suggests that recent radiations are obscuring deep time patterns in the evolution of birds. Metrics from different models can be used in conjunction to provide more valuable insights than simply finding the model with the highest relative fit. PMID- 26257157 TI - Evaluation of biological activity of quantum dots in a microsystem. AB - The presented work aimed at systematic investigation of biological activity of CdSex S1- x /ZnS and CdSe/ZnS quantum dots (QDs), whose surface was modified with different ligands. For these studies, we used a microfluidic system combined with fluorescence microscopy techniques, which enabled analysis of cells' morphology, viability, and QDs uptake. PDMS and glass-based microfluidic system enabled the precise control of the cell environment, allowed to examine five replications of each tested QDs concentrations (statistically significant number), monitor multiple cellular events, and avoid manual preparation of QDs dilutions. We investigated the influence of the core composition and the type of surface modifiers on QDs toxicity. We also determined whether the examined nanoparticles penetrate into the cells. For all tested nanoparticles, the decrease of cells' viability was observed when increasing nanoparticles concentration. The decrease of live cells' number in microchambers and the accumulation of the nanoparticles around cultured cells were observed. The effect of hydrocarbon chain length of surface modifiers and QDs core composition on the cell viability was confirmed in our tests. PMID- 26257158 TI - Efficiency of photodynamic therapy on WM35 melanoma with synthetic porphyrins: Role of chemical structure, intracellular targeting and antioxidant defense. AB - Photodynamic therapy (PDT) could be an adjuvant therapy in melanoma, an aggressive cancer that arises from melanocytes. Several reports showed encouraging results of the efficacy of PDT in melanoma on experimental models and in clinical trials. Therefore, we studied the efficacy of two derivatives of tetraphenylporphyrin (TPP): meso-5,10,15,20-tetrakis (4-hydroxyphenyl) porphyrin (THOPP) and meso-5-(4-hydroxyphenyl)-10,15,20-tris (4-methoxyphenyl) porphyrin (THOMPP) as photosensitizers for PDT, compared to FDA approved delta aminolevulinic acid (ALA) against a lightly pigmented, melanoma cell line, WM35, in vitro. Both porphyrins were more efficient as photosensitizers, compared to ALA, without dark toxicity. The efficiency depended on the intracellular localization and the molecule structure. THOPP, the most efficient porphyrin localized mainly in mitochondria, while THOMPP accumulated in lysosomes; both showed melanosomal localization. The symmetric THOPP molecule was able to generate increased oxidative stress damage and apoptosis. THOPP also induced a low effect on the defense mechanisms like antioxidant enzyme SOD (superoxide dismutase), NF-kB (nuclear transcription factor kB) activation and MITF (microphthalmia transcription factor). The lower efficiency of the asymmetric molecule, THOMPP was probably due to a diminished photoactivation, which led to a lower ROS induced damage, combined with higher activation of the defense mechanisms. PMID- 26257159 TI - Neurological Toxicity of Individual and Mixtures of Low Dose Arsenic, Mono and Di (n-butyl) Phthalates on Sub-Chronic Exposure to Mice. AB - The objective of this study was to evaluate the toxicity of individual and mixtures of di(n-butyl) phthalates (DBP) and their active metabolite monobutyl phthalate (MBP) and arsenic (As) on spatial cognition associated with hippocampal apoptosis in mice. Mice were exposed, individually or in combination, to DBP (50 mg/kg body weight, intragastrically), MBP (50 mg/kg body weight, intragastrically), and As (10 mg/L, per os) for 8 weeks. The Morris water maze test showed that mice exposed to DBP/MBP combined with As exhibited longer escape latencies and the lower average number of crossing the platform. The As content in the hippocampus after As exposure increased as compared to those without As exposure. In mice exposed to DBP/MBP combined with As, pathological alterations and oxidative damage to the hippocampus were found. Expression of apoptosis related protein: Bax and caspase-3 were significantly increased in the hippocampus, while there was no significant change in expression of Bcl-2. The results suggested that DBP and MBP combined with As can induce spatial cognitive deficits through altering the expression of apoptosis-related protein and As played a critical role in cognition impairments. And the joint exposure has antagonistic effect. PMID- 26257160 TI - Heat Shock Protein Alteration in the Gastrointestinal Tract Tissues of Chickens Exposed to Arsenic Trioxide. AB - Arsenic (As) is widely distributed in our living environment and is useful for industry, agriculture, medical treatment, and other fields. Arsenic trioxide (As2O3) is an existing form of As. Exposure to As2O3 has a toxic effect on humans and animals. It not only leads to skin cancer, peripheral vascular disease, hyperkeratosis, etc. but also interferes with the functioning of the gastrointestinal tract. The gastrointestinal tract is an important organ for animals to transform the food they eat into the nutrients their body needs for maintenance and growth. Heat shock proteins (Hsps) exist in the non-stress normal cells and their expression increases under stimuli. Therefore, we wonder whether the "stimulus" of As2O3 could change the messenger RNA (mRNA) abundance and expression level of Hsps in the gastrointestinal tract of birds. To investigate the relation between arseniasis and Hsp alterations in the chicken's gastrointestinal tract induced by an As2O3-supplemented diet, we selected 72 one day-old male Hy-line chickens and randomly divided them into four groups. They were fed either a commercial diet or an As2O3-supplemented diet containing 7.5, 15, and 30 mg/kg As2O3. The experiment lasted for 90 days, and gastrointestinal tract tissue samples (gizzard, glandular stomach, duodenum, jejunum, ileum, cecum, and rectum) were collected at 30, 60, and 90 days. The mRNA contents of Hsps (including Hsp27, Hsp40, Hsp60, Hsp70, and Hsp90) were examined by real-time PCR (RT-PCR). The correlation between As2O3 and Hsp genes was assessed. In addition, the protein expression levels of Hsp60 and Hsp70 in the gastrointestinal tract tissue samples were measured by western blot. The results indicated that the mRNA expression levels and the Hsp expression levels in the gastrointestinal tract tissues of chickens with As2O3 supplementation increased at different time points in a dose-dependent manner (p < 0.05 or p < 0.01). These data suggested that arseniasis influenced the mRNA abundance of Hsp27, Hsp40, Hsp60, Hsp70, and Hsp90 and the protein expression levels of Hsp60 and Hsp70 in the chicken's gastrointestinal tract tissues. PMID- 26257161 TI - Vagally Mediated Analgesia: Breath-Holding during Exhalation as a Simple Manipulation to Reduce Pain Perception-Reyes Del Paso et al. Pain Medicine 2015. PMID- 26257162 TI - LSD enhances the emotional response to music. AB - RATIONALE: There is renewed interest in the therapeutic potential of psychedelic drugs such as lysergic acid diethylamide (LSD). LSD was used extensively in the 1950s and 1960s as an adjunct in psychotherapy, reportedly enhancing emotionality. Music is an effective tool to evoke and study emotion and is considered an important element in psychedelic-assisted psychotherapy; however, the hypothesis that psychedelics enhance the emotional response to music has yet to be investigated in a modern placebo-controlled study. OBJECTIVES: The present study sought to test the hypothesis that music-evoked emotions are enhanced under LSD. METHODS: Ten healthy volunteers listened to five different tracks of instrumental music during each of two study days, a placebo day followed by an LSD day, separated by 5-7 days. Subjective ratings were completed after each music track and included a visual analogue scale (VAS) and the nine-item Geneva Emotional Music Scale (GEMS-9). RESULTS: Results demonstrated that the emotional response to music is enhanced by LSD, especially the emotions "wonder", "transcendence", "power" and "tenderness". CONCLUSIONS: These findings reinforce the long-held assumption that psychedelics enhance music-evoked emotion, and provide tentative and indirect support for the notion that this effect can be harnessed in the context of psychedelic-assisted psychotherapy. Further research is required to test this link directly. PMID- 26257163 TI - Cue reactivity and its relation to craving and relapse in alcohol dependence: a combined laboratory and field study. AB - The present study investigated the nature of physiological cue reactivity and craving in response to alcohol cues among alcohol-dependent patients (N = 80) who were enrolled in detoxification treatment. Further, the predictive value with regard to future drinking of both the magnitude of the physiological and craving response to alcohol cues while in treatment and the degree of alcohol-cue exposure in patients' natural environment was assessed. Physiological reactivity and craving in response to experimental exposure to alcohol and soft drink advertisements were measured during detoxification treatment using heart rate variability and subjective rating of craving. Following discharge, patients monitored exposure to alcohol advertisements for five consecutive weeks with a diary and were followed up with an assessment of relapse at 5 weeks and 3 months post-discharge. The results indicated that the presence of alcohol cues such as the portrayal of the drug and drinking behaviour induced physiological cue reactivity and craving. Additionally, cue reactivity and craving were positively correlated, and cue reactivity was larger for patients with shorter histories of alcohol dependence. Further, patients reported a substantial daily exposure to alcohol cues. The magnitude of cue reactivity and the craving response to alcohol cues at baseline and degree of exposure to alcohol cues in patients' natural environment did not predict relapse. It is concluded that the presence of alcohol cues such as portrayal of alcoholic beverages and drinking behaviour induces cue reactivity and craving in alcohol dependence through a conditioned appetitive response. PMID- 26257164 TI - Ultrasound-assisted extraction method for the simultaneous determination of emerging contaminants in freshwater sediments. AB - Sediments are the fate of several emerging organic contaminants, such as pharmaceuticals, personal care products and hormones, and therefore an important subject in environmental monitoring studies. In the present work, a simple and sensitive method was developed, validated and applied for the simultaneous extraction of atenolol, caffeine, carbamazepine, diclofenac, ibuprofen, naproxen, propranolol, triclosan, estrone, 17-beta-estradiol and 17-alpha-ethinylestradiol using ultrasound-assisted extraction from freshwater sediment samples followed by solid-phase extraction clean-up and liquid chromatography with tandem mass spectrometry detection. The solvent type and extraction pH were evaluated to obtain the highest recoveries of the compounds. The best method shows absolute recoveries between 54.0 and 94.4% at 50 ng/g concentration. The method exhibits good precision with relative standard deviation ranging from 1.0-16%. The detection and quantification limits ranged from 0.006-0.067 and 0.016-0.336 ng/g, respectively. The developed method was successfully applied to freshwater sediment samples collected from different sites in Jundiai River basin of Sao Paulo State, Brazil. The compounds atenolol, caffeine, propranolol and triclosan were detected in all the sampling sites with concentrations of 13.8, 41.0, 28.5 and 176 ng/g, respectively. PMID- 26257165 TI - Effects of TNF-alpha blocking on experimental periodontitis and type 2 diabetes in obese diabetic Zucker rats. AB - OBJECTIVE: Tumour necrosis factor alpha (TNF-alpha) is considered a key signalling modulator in the pathogenesis of both periodontitis (PD) and type 2 diabetes mellitus (DM2). This study aims at elucidating the effect of TNF-alpha blocking on the interplay between PD and DM2. METHODS: Obese diabetic Zucker rats and their lean littermates were divided into five treatment groups with or without periodontitis. Anti-TNF-alpha treatment was provided with Etanercept injections. Diabetic state was evaluated by oral glucose tolerance test, the homeostatic model assessment, free fatty acids and blood glucose. Systemic inflammation was assessed by measurement of interleukin (IL)-1beta, IL-6 and TNF alpha in plasma. Kidney complications were evaluated by real-time rtPCR, creatinine clearance rate, urinary albumin excretion and increase in weight. PD was evaluated by registration of alveolar bone level. RESULTS: After 4 weeks the diabetic state was modified by Etanercept treatment with lower insulin levels and lower homeostatic model assessment. Furthermore, while kidney complications were reduced by Etanercept treatment, PD had no effect. PD was influenced by diabetic state, but the impact was attenuated by Etanercept treatment. CONCLUSION: In this study anti-TNF-alpha treatment improved glucose tolerance and compensated for the increased periodontal disease in obese diabetic Zucker. PD did not influence diabetic parameters assessed including complications of the rats kidneys. PMID- 26257166 TI - Tenofovir/entecavir monotherapy after hepatitis B immunoglobulin withdrawal is safe and effective in the prevention of hepatitis B in liver transplant recipients. AB - BACKGROUND AND AIMS: Combination of hepatitis B immunoglobulin (HBIG) and a nucleos(t)ide analog (NA) is considered the standard of care for prophylaxis of hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, use of lifelong HBIG has significant limitations. We evaluated the efficacy and safety of entecavir (ETV) or tenofovir disoproxil fumarate (TDF) after withdrawal of HBIG in patients who had been under HBIG-regimen prophylaxis post LT. METHODS: Patients at low risk of recurrence were eligible for HBIG discontinuation (fulminant HBV hepatitis, co-infection with hepatitis D virus, and hepatitis B e antigen-negative cirrhotic patients with HBV DNA levels <300 copies/mL). All patients had received HBIG, with or without NA, for at least 12 months after LT. After HBIG discontinuation, they continued with ETV or TDF monotherapy. Patients were followed up with HBV serum markers and evaluation of renal function. RESULTS: Between September 2011 and June 2014, 58 liver transplant recipients were converted to TDF (31, 53%) or ETV (27, 47%). Mean follow-up after conversion was 28 +/- 5 months (range 13-36 months). Five patients (8.6%) developed detectable hepatitis B surface antigen at 7, 9, 13, 15, and 22 months after HBIG discontinuation. However, in every case seroconversion was transitory, serum HBV DNA was undetectable, with no clinical manifestations of HBV recurrence. No adverse effects were observed or dose reductions required associated with ETV or TDF. CONCLUSIONS: Maintenance therapy with newer NAs, after discontinuation of HBIG prophylaxis, was safe and effective, with a low rate of serological recurrence and no evident clinical, biochemical, or virological consequences. PMID- 26257167 TI - An integrated analysis of phenotypic selection on insect body size and development time. AB - Most studies of phenotypic selection do not estimate selection or fitness surfaces for multiple components of fitness within a unified statistical framework. This makes it difficult or impossible to assess how selection operates on traits through variation in multiple components of fitness. We describe a new generation of aster models that can evaluate phenotypic selection by accounting for timing of life-history transitions and their effect on population growth rate, in addition to survival and reproductive output. We use this approach to estimate selection on body size and development time for a field population of the herbivorous insect, Manduca sexta (Lepidoptera: Sphingidae). Estimated fitness surfaces revealed strong and significant directional selection favoring both larger adult size (via effects on egg counts) and more rapid rates of early larval development (via effects on larval survival). Incorporating the timing of reproduction and its influence on population growth rate into the analysis resulted in larger values for size in early larval development at which fitness is maximized, and weaker selection on size in early larval development. These results illustrate how the interplay of different components of fitness can influence selection on size and development time. This integrated modeling framework can be readily applied to studies of phenotypic selection via multiple fitness components in other systems. PMID- 26257168 TI - In-depth proteomics approach of secretome to identify novel biomarker for sepsis in LPS-stimulated endothelial cells. AB - Sepsis and septic shock, which are conditions triggered by infection, occur with high incidence in emergency departments and are among the most common causes of death in hospitalized patients worldwide. Therefore, the identification of sepsis biomarkers for the rapid diagnosis is a major goal for researchers in the field of critical care. Endothelial cells play a pivotal role in orchestrating the inflammatory response triggered by sepsis. In this study, we used proteomics to investigate the secretome of EA.hy926 endothelial cells following lipopolysaccharide (LPS) stimulation with 1 MUg/mL LPS for 12 or 24 h. SILAC in cell cultures and an online 2D-LC-MS/MS system were used to analyze the secretome dynamics in response to LPS. We found that 22 of the 77 secreted proteins identified in both the presence and absence of LPS and that 19 of the secreted proteins were quantified more strongly after LPS treatment for 24 h than after treatment for 12 h. By Gene Ontology and KEGG pathway analyses, we found that proteins related to the regulation of the actin cytoskeleton showed the highest secretion response to LPS stimulation. Out of the 19 candidate proteins, we focused on moesin, which is involved in the function of endothelial cells, and confirmed its amount in cellular lysates and media taken from primary human umbilical vein endothelial cells treated with LPS. To our knowledge, this study provides the first in-depth analysis of the LPS-induced secretome in human endothelial cells, and we propose 19 new biomarker candidates for sepsis, including moesin. PMID- 26257169 TI - Metabolic Damage and Premature Thymus Aging Caused by Stromal Catalase Deficiency. AB - T lymphocytes are essential mediators of immunity that are produced by the thymus in proportion to its size. The thymus atrophies rapidly with age, resulting in progressive diminution of new T cell production. This decreased output is compensated by duplication of existing T cells, but it results in gradual dominance by memory T cells and decreased ability to respond to new pathogens or vaccines. Here, we show that accelerated and irreversible thymic atrophy results from stromal deficiency in the reducing enzyme catalase, leading to increased damage by hydrogen peroxide generated by aerobic metabolism. Genetic complementation of catalase in stromal cells diminished atrophy, as did chemical antioxidants, thus providing a mechanistic link between antioxidants, metabolism, and normal immune function. We propose that irreversible thymic atrophy represents a conventional aging process that is accelerated by stromal catalase deficiency in the context of an intensely anabolic (lymphoid) environment. PMID- 26257170 TI - Neutrophils Regulate Humoral Autoimmunity by Restricting Interferon-gamma Production via the Generation of Reactive Oxygen Species. AB - Here, we examine the mechanism by which plasmacytoid dendritic cells (pDCs) and type I interferons promote humoral autoimmunity. In an amyloid-induced experimental autoimmune model, neutrophil depletion enhanced anti-nuclear antibody development, which correlated with heightened IFN-gamma production by natural killer (NK) cells. IFN-alpha/beta produced by pDCs activated NK cells via IL-15 induction. Neutrophils released reactive oxygen species (ROS), which negatively modulated the levels of IL-15, thereby inhibiting IFN-gamma production. Mice deficient in NADPH oxidase 2 produced increased amounts of IFN gamma and developed augmented titers of autoantibodies. Both the pDC-IFN alpha/beta pathway and IFN-gamma were indispensable in stimulating humoral autoimmunity. Male NZB/W F1 mice expressed higher levels of superoxide than their female lupus-prone siblings, and depletion of neutrophils resulted in spontaneous NK cell and autoimmune B cell activation. Our findings suggest a regulatory role for neutrophils in vivo and highlight the importance of an NK-IFN-gamma axis downstream of the pDC-IFN-alpha/beta pathway in systemic autoimmunity. PMID- 26257171 TI - Macrophages Contribute to the Spermatogonial Niche in the Adult Testis. AB - The testis produces sperm throughout the male reproductive lifespan by balancing self-renewal and differentiation of spermatogonial stem cells (SSCs). Part of the SSC niche is thought to lie outside the seminiferous tubules of the testis; however, specific interstitial components of the niche that regulate spermatogonial divisions and differentiation remain undefined. We identified distinct populations of testicular macrophages, one of which lies on the surface of seminiferous tubules, in close apposition to areas of tubules enriched for undifferentiated spermatogonia. These macrophages express spermatogonial proliferation- and differentiation-inducing factors, such as colony-stimulating factor 1 (CSF1) and enzymes involved in retinoic acid (RA) biosynthesis. We show that transient depletion of macrophages leads to a disruption in spermatogonial differentiation. These findings reveal an unexpected role for macrophages in the spermatogonial niche in the testis and raise the possibility that macrophages play previously unappreciated roles in stem/progenitor cell regulation in other tissues. PMID- 26257174 TI - Oocyte Factors Suppress Mitochondrial Polynucleotide Phosphorylase to Remodel the Metabolome and Enhance Reprogramming. AB - Oocyte factors not only drive somatic cell nuclear transfer reprogramming but also augment the efficiency and quality of induced pluripotent stem cell (iPSC) reprogramming. Here, we show that the oocyte-enriched factors Tcl1 and Tcl1b1 significantly enhance reprogramming efficiency. Clonal analysis of pluripotency biomarkers further show that the Tcl1 oocyte factors improve the quality of reprogramming. Mechanistically, we find that the enhancement effect of Tcl1b1 depends on Akt, one of its putative targets. In contrast, Tcl1 suppresses the mitochondrial polynucleotide phosphorylase (PnPase) to promote reprogramming. Knockdown of PnPase rescues the inhibitory effect from Tcl1 knockdown during reprogramming, whereas PnPase overexpression abrogates the enhancement from Tcl1 overexpression. We further demonstrate that Tcl1 suppresses PnPase's mitochondrial localization to inhibit mitochondrial biogenesis and oxidation phosphorylation, thus remodeling the metabolome. Hence, we identified the Tcl1 PnPase pathway as a critical mitochondrial switch during reprogramming. PMID- 26257173 TI - MBNL Sequestration by Toxic RNAs and RNA Misprocessing in the Myotonic Dystrophy Brain. AB - For some neurological disorders, disease is primarily RNA mediated due to expression of non-coding microsatellite expansion RNAs (RNA(exp)). Toxicity is thought to result from enhanced binding of proteins to these expansions and depletion from their normal cellular targets. However, experimental evidence for this sequestration model is lacking. Here, we use HITS-CLIP and pre-mRNA processing analysis of human control versus myotonic dystrophy (DM) brains to provide compelling evidence for this RNA toxicity model. MBNL2 binds directly to DM repeat expansions in the brain, resulting in depletion from its normal RNA targets with downstream effects on alternative splicing and polyadenylation. Similar RNA processing defects were detected in Mbnl compound-knockout mice, highlighted by dysregulation of Mapt splicing and fetal tau isoform expression in adults. These results demonstrate that MBNL proteins are directly sequestered by RNA(exp) in the DM brain and introduce a powerful experimental tool to evaluate RNA-mediated toxicity in other expansion diseases. PMID- 26257172 TI - Exome Sequence Analysis Suggests that Genetic Burden Contributes to Phenotypic Variability and Complex Neuropathy. AB - Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous distal symmetric polyneuropathy. Whole-exome sequencing (WES) of 40 individuals from 37 unrelated families with CMT-like peripheral neuropathy refractory to molecular diagnosis identified apparent causal mutations in ~ 45% (17/37) of families. Three candidate disease genes are proposed, supported by a combination of genetic and in vivo studies. Aggregate analysis of mutation data revealed a significantly increased number of rare variants across 58 neuropathy-associated genes in subjects versus controls, confirmed in a second ethnically discrete neuropathy cohort, suggesting that mutation burden potentially contributes to phenotypic variability. Neuropathy genes shown to have highly penetrant Mendelizing variants (HPMVs) and implicated by burden in families were shown to interact genetically in a zebrafish assay exacerbating the phenotype established by the suppression of single genes. Our findings suggest that the combinatorial effect of rare variants contributes to disease burden and variable expressivity. PMID- 26257175 TI - Serotonin Mediates Maternal Effects and Directs Developmental and Behavioral Changes in the Progeny of Snails. AB - Many organisms survive in constantly changing environments, including cycling seasons. Developing embryos show remarkable instant adaptations to the variable environmental challenges they encounter during their adult life, despite having no direct contact with the changing environment until after birth or hatching. The mechanisms by which such non-genetic information is transferred to the developing embryos are largely unknown. Here, we address this question by using a freshwater pond snail (Lymnaea stagnalis) as a model system. This snail normally lives in a seasonal climate, and the seasons define its locomotion, feeding, and reproductive behavior. We discovered that the serotonergic system plays a crucial role in transmitting a non-genetic instructive signal from mother to progeny. This maternal serotonin-based signal functions in embryos during a short time window at exclusively early pre-neural developmental stages and modulates the dynamics of embryonic and juvenile growth, feeding behavior, and locomotion. PMID- 26257176 TI - Complete Loss of Netrin-1 Results in Embryonic Lethality and Severe Axon Guidance Defects without Increased Neural Cell Death. AB - Netrin-1 regulates cell migration and adhesion during the development of the nervous system, vasculature, lung, pancreas, muscle, and mammary gland. It is also proposed to function as a dependence ligand that inhibits apoptosis; however, studies disagree regarding whether netrin-1 loss-of-function mice exhibit increased cell death. Furthermore, previously studied netrin-1 loss-of function gene-trap mice express a netrin-1-beta-galactosidase protein chimera with potential for toxic gain-of-function effects, as well as a small amount of wild-type netrin-1 protein. To unambiguously assess loss of function, we generated netrin-1 floxed and netrin-1 null mouse lines. Netrin-1(-/-) mice die earlier and exhibit more severe axon guidance defects than netrin-1 gene-trap mice, revealing that complete loss of function is more severe than previously reported. Netrin-1(-/-) embryos also exhibit increased expression of the netrin receptors DCC and neogenin that are proposed dependence receptors; however, increased apoptosis was not detected, inconsistent with netrin-1 being an essential dependence receptor ligand in the embryonic spinal cord. PMID- 26257177 TI - Heterotypic Signals from Neural HSF-1 Separate Thermotolerance from Longevity. AB - Integrating stress responses across tissues is essential for the survival of multicellular organisms. The metazoan nervous system can sense protein-misfolding stress arising in different subcellular compartments and initiate cytoprotective transcriptional responses in the periphery. Several subcellular compartments possess a homotypic signal whereby the respective compartment relies on a single signaling mechanism to convey information within the affected cell to the same stress-responsive pathway in peripheral tissues. In contrast, we find that the heat shock transcription factor, HSF-1, specifies its mode of transcellular protection via two distinct signaling pathways. Upon thermal stress, neural HSF-1 primes peripheral tissues through the thermosensory neural circuit to mount a heat shock response. Independent of this thermosensory circuit, neural HSF-1 activates the FOXO transcription factor, DAF-16, in the periphery and prolongs lifespan. Thus a single transcription factor can coordinate different stress response pathways to specify its mode of protection against changing environmental conditions. PMID- 26257178 TI - Overlapping Requirements for Tet2 and Tet3 in Normal Development and Hematopoietic Stem Cell Emergence. AB - The Tet family of methylcytosine dioxygenases (Tet1, Tet2, and Tet3) convert 5 methylcytosine to 5-hydroxymethylcytosine. To date, functional overlap among Tet family members has not been examined systematically in the context of embryonic development. To clarify the potential for overlap among Tet enzymes during development, we mutated the zebrafish orthologs of Tet1, Tet2, and Tet3 and examined single-, double-, and triple-mutant genotypes. Here, we identify Tet2 and Tet3 as the major 5-methylcytosine dioxygenases in the zebrafish embryo and uncover a combined requirement for Tet2 and Tet3 in hematopoietic stem cell (HSC) emergence. We demonstrate that Notch signaling in the hemogenic endothelium is regulated by Tet2/3 prior to HSC emergence and show that restoring expression of the downstream gata2b/scl/runx1 transcriptional network can rescue HSCs in tet2/3 double mutant larvae. Our results reveal essential, overlapping functions for tet genes during embryonic development and uncover a requirement for 5hmC in regulating HSC production. PMID- 26257179 TI - Nuclear Fractionation Reveals Thousands of Chromatin-Tethered Noncoding RNAs Adjacent to Active Genes. AB - A number of long noncoding RNAs (lncRNAs) have been reported to regulate transcription via recruitment of chromatin modifiers or bridging distal enhancer elements to gene promoters. However, the generality of these modes of regulation and the mechanisms of chromatin attachment for thousands of unstudied human lncRNAs remain unclear. To address these questions, we performed stringent nuclear fractionation coupled to RNA sequencing. We provide genome-wide identification of human chromatin-associated lncRNAs and demonstrate tethering of RNA to chromatin by RNAPII is a pervasive mechanism of attachment. We also uncovered thousands of chromatin-enriched RNAs (cheRNAs) that share molecular properties with known lncRNAs. Although distinct from eRNAs derived from active prototypical enhancers, the production of cheRNAs is strongly correlated with the expression of neighboring protein-coding genes. This work provides an updated framework for nuclear RNA organization that includes a large chromatin-associated transcript population correlated with active genes and may prove useful in de novo enhancer annotation. PMID- 26257180 TI - Role of DNA Methylation in Modulating Transcription Factor Occupancy. AB - Although DNA methylation is commonly invoked as a mechanism for transcriptional repression, the extent to which it actively silences transcription factor (TF) occupancy sites in vivo is unknown. To study the role of DNA methylation in the active modulation of TF binding, we quantified the effect of DNA methylation depletion on the genomic occupancy patterns of CTCF, an abundant TF with known methylation sensitivity that is capable of autonomous binding to its target sites in chromatin. Here, we show that the vast majority (>98.5%) of the tens of thousands of unoccupied, methylated CTCF recognition sequences remain unbound upon abrogation of DNA methylation. The small fraction of sites that show methylation-dependent binding in vivo are in turn characterized by highly variable CTCF occupancy across cell types. Our results suggest that DNA methylation is not a primary groundskeeper of genomic TF landscapes, but rather a specialized mechanism for stabilizing intrinsically labile sites. PMID- 26257181 TI - Aubergine iCLIP Reveals piRNA-Dependent Decay of mRNAs Involved in Germ Cell Development in the Early Embryo. AB - The Piwi-interacting RNA (piRNA) pathway plays an essential role in the repression of transposons in the germline. Other functions of piRNAs such as post transcriptional regulation of mRNAs are now emerging. Here, we perform iCLIP with the PIWI protein Aubergine (Aub) and identify hundreds of maternal mRNAs interacting with Aub in the early Drosophila embryo. Gene expression profiling reveals that a proportion of these mRNAs undergo Aub-dependent destabilization during the maternal-to-zygotic transition. Strikingly, Aub-dependent unstable mRNAs encode germ cell determinants. iCLIP with an Aub mutant that is unable to bind piRNAs confirms piRNA-dependent binding of Aub to mRNAs. Base pairing between piRNAs and mRNAs can induce mRNA cleavage and decay that are essential for embryonic development. These results suggest general regulation of maternal mRNAs by Aub and piRNAs, which plays a key developmental role in the embryo through decay and localization of mRNAs encoding germ cell determinants. PMID- 26257182 TI - Graphene oxide quantum dots@silver core-shell nanocrystals as turn-on fluorescent nanoprobe for ultrasensitive detection of prostate specific antigen. AB - We report a fluorescent turn-on nanoprobe for ultrasensitive detection of prostate specific antigen (PSA) based on graphene oxide quantum dots@silver (GQDs@Ag) core-shell nanocrystals. The success of this work relies on the assembly of quantities of GQDs in one GQDs@Ag probe, which makes the ratio of probe to target significantly increased and thus enables the fluorescent signal enhancement. When the silver shell was removed via oxidative etching using hydrogen peroxide (H2O2), the incorporated GQDs could be readily released and the whole process caused little change to their fluorescence performance. We tested the probe for the ultrasensitive detection of PSA based on the sandwich protocol of immunosensors. In particular, magnetic beads (MBs) were employed to immobilize anti-PSA antibody (Ab1) and acted as a separable capture probe, while GQDs@Ag was used as detection probe by linking antibody (Ab2). The developed immunosensor showed a good linear relationship between the fluorescence intensity and the concentration of PSA in the range from 1 pg/mL to 20 ng/mL with a detection limit of 0.3 pg/mL. The immunosensor used for the analysis of clinical serum samples exhibited satisfactory results, which demonstrated its potential for practical diagnostic applications. This method provides a possible solution to the application of GQDs in immunosensing and could be potentially extended to other similar systems. PMID- 26257183 TI - Ultrasensitive electrochemical immunosensor for PSA biomarker detection in prostate cancer cells using gold nanoparticles/PAMAM dendrimer loaded with enzyme linked aptamer as integrated triple signal amplification strategy. AB - In the present study, a triple signal amplification strategy was developed for ultrasensitive immunosensing of prostate-specific antigen (PSA) tumor marker. The proposed system was achieved by modification of glassy carbon electrode with graphene oxide/chitosan film and covalently attached of monoclonal PSA antibody and thionine as redox probe onto the modified electrode surface. Then, immunosensing was completed using sandwich-type immunoreaction of the PSA-antigen between anti-PSA immobilized on the graphene/chitosan interface and PSA-aptamer. For improve the sensitivity, polyamidoamine dendrimer-encapsulated gold nanoparticles (AuNPs-PAMAM) was used for covalent attachment of PSA-aptamer and HRP linked aptamer (Au-PAMA/aptamer-HRP) as electrochemical label in the sandwich format and electrocatalytic reduction of H2O2 in the presence of enzymatically oxidized thionine was measured. Under optimized condition, the obtained detection limit and linear concentration range were 10 fg ml(-1)(S/N=3) and 0.1 pg ml(-1) to 90 ngml(-1) respectively, using differential pulse voltammetry as measuring technique. In addition, electrochemical impedance spectroscopy (EIS) was used as simple, rapid, low cost label free analytical technique for PSA measurement with detection limit of 5 pg ml(-1) at concentration range up to 35 ng ml(-1). Finally, the immunosensor is used to PSA detection in human serum and prostate tissue samples and the obtained result is well agreed with the values obtained by the standard ELISA method. The obtained results indicate the proposed immunosensor can be used for monitor the differences in PSA concentration in cancer tissue samples which holds great promise in clinical screening of cancer biomarkers. PMID- 26257184 TI - A self-enhanced electrochemiluminescence immunosensor based on L-Lys Ru(dcbpy)3(2+) functionalized porous six arrises column nanorods for detection of CA15-3. AB - In this work, a new manganese ions doped zinc oxide porous six arrises column nanorods was rapidly synthesized with L-Lys as the precipitating and capping agent (L-Lys/Mn-ZnONRs). The as-synthesized L-Lys/Mn-ZnONRs exhibited large specific surface area and high ferromagnetism, which could serve as excellent nanocarrier. Meanwhile, due to the outstanding conductivity and biocompatibility, platinum nanoparticles (PtNPs) were decorated on the surface of L-Lys/Mn-ZnONRs by Pt-N bond to form PtNPs/L-Lys/Mn-ZnONRs complexes. After that, the obtained complexes were used to immobilize abundant tris (4,4'-dicarboxylicacid-2,2' bipyridyl) ruthenium(II) dichloride (Ru(dcbpy)3(2+)) and detection antibody for construction of sandwiched electrochemiluminescence (ECL) immunosensor. Coincidentally, L-Lys not only acted as the precipitating and capping agent to control shape and size of L-Lys/Mn-ZnONRs, but also acted as a co-reactant of Ru(dcbpy)3(2+) to efficiently amplify the ECL signal. Importantly, L-Lys had free amino group which could link with Ru(dcbpy)3(2+)via amide bond to form a self enhanced ECL complex. Through this way, the electron transfer path between luminophore and co-reactant reagent was shortened and the energy loss of luminophore was lessened. Consequently, the prepared ECL immunosensor showed excellent performance for the detection of carbohydrate antigen 15-3 in the range from 0.05 U/mL to 120 U/mL with a detection limit of 0.014 U/mL (S/N=3) and a correlation coefficient of R=0.9977. Moreover, the prepared ECL immunosensor had good stability, excellent selectivity and satisfactory reproducibility. PMID- 26257185 TI - [G3T]5/Tb(3+) based DNA biosensor with target DNA-triggered autocatalytic multi cycle-amplification and magnetic nanoparticles assisted-background-lowered. AB - Due to terbium's unique photophysical properties, nucleic-acid-sensitized terbium (DNA/Tb(3+)) bioluminescent system becomes a potential candidate for the fabrication of DNA biosensors. However, the low sensitivity of DNA/Tb(3+) bioluminescent system limits its development. In this paper, a strategy combining autocatalytic multi-cycle-amplification (including exonuclease III (exo III) aided and Zn(2+)-requiring DNAzyme-assisted target recycling amplifications) and magnetic nanoparticles assisted-background-lowering to improve the sensitivity of DNA/Tb(3+) bioluminescent system is presented for sensitive detection of target DNA (tDNA). The DNA/Tb(3+) bioluminescent system was investigated by ultraviolet visible (UV-vis) absorption and luminescence spectra. The possible conjugation mechanism and mode of DNA with Tb(3+) were discussed. The autocatalytic multi cycle-amplification effect was investigated by the comparison of the luminescence. The carboxylation-functionalized Fe3O4-magnetic nanoparticles (MNPs) were characterized and its role in background lowering was proved. As a result, with the designed protocol, the detection limit for the tDNA detection reached a low level to aM, which is especially exciting for the DNA/Tb(3+) bioluminescent system. In the process, due to the separation effect of MNPs, the assay solution was purified to avoid the nonspecific luminescence of DNA/Tb(3+), not only lowering the background signal greatly (about five times lower than that without the use of MNPs but also improving the reproducibility and stability. We hope that our attempt in this field will not only extend the application of DNA/Tb(3+) luminescent system in biosensing areas but also open the road to adaptation of the protocols to other related analytes. PMID- 26257186 TI - Electrochemical DNA sensor for anthrax toxin activator gene atxA-detection of PCR amplicons. AB - We report the DNA probe functionalized electrochemical genosensor for the detection of Bacillus anthracis, specific towards the regulatory gene atxA. The DNA sensor is fabricated on electrochemically deposited gold nanoparticle on self assembled layer of (3-Mercaptopropyl) trimethoxysilane (MPTS) on GC electrode. DNA hybridization is monitored by differential pulse voltammogram (DPV). The modified GC electrode is characterized by atomic force microscopy (AFM), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) method. We also quantified the DNA probe density on electrode surface by the chronocoulometric method. The detection is specific and selective for atxA gene by DNA probe on the electrode surface. No report is available for the detection of B. anthracis by using atxA an anthrax toxin activator gene. In the light of real and complex sample, we have studied the PCR amplicons of 303, 361 and 568 base pairs by using symmetric and asymmetric PCR approaches. The DNA probe of atxA gene efficiently hybridizes with different base pairs of PCR amplicons. The detection limit is found to be 1.0 pM (S/N ratio=3). The results indicate that the DNA sensor is able to detect synthetic target as well as PCR amplicons of different base pairs. PMID- 26257187 TI - Stretchable biofuel cell with enzyme-modified conductive textiles. AB - A sheet-type, stretchable biofuel cell was developed by laminating three components: a bioanode textile for fructose oxidation, a hydrogel sheet containing fructose as fuel, and a gas-diffusion biocathode textile for oxygen reduction. The anode and cathode textiles were prepared by modifying carbon nanotube (CNT)-decorated stretchable textiles with fructose dehydrogenase (FDH) and bilirubin oxidase (BOD), respectively. Enzymatic reaction currents of anode and cathode textiles were stable for 30 cycles of 50% stretching, with initial loss of 20-30% in the first few cycles due to the partial breaking of the CNT network at the junction of textile fibers. The assembled laminate biofuel cell showed power of ~0.2 mW/cm(2) with 1.2 kOmega load, which was stable even at stretched, twisted, and wrapped forms. PMID- 26257188 TI - Ultrasensitive electrochemical biosensor based on reduced graphene oxide tetraethylene pentamine-BMIMPF6 hybrids for the detection of alpha2,6-sialylated glycans in human serum. AB - In this paper, a simple, ultrasensitive and label-free electrochemical alpha2,6 sialylated glycans biosensor based on reduced graphene oxide-tetraethylene pentamine-1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6) hybrids was developed. Due to the abundance of amino groups from reduced graphene oxide tetraethylene pentamine (rGO-TEPA) and the electrostatic interaction of BMIMPF6, bimetallic gold platinum alloy nanoparticles (AuPtNPs) were densely adsorbed onto the surface of the nanocomposite, providing a large surface area available for the immobilization of Sambucus nigra agglutinin (SNA). AuPtNPs have excellent conductivity and catalytic activity, which can promote electron transfer between the electrolyte solution and the surface of electrode and can enhance the sensitivity of biosensor. SNA, which specifically binds alpha2,6-sialylated glycans, was covalently immobilized on AuPtNPs for specific detection of alpha2,6 sialylated glycans in human serum. Under optimal experimental conditions, amperometric response changes were used to detect alpha2,6-sialylated glycans with a broad linear range of 10 fg mL(-1) -1 MUg mL(-1) and a low detection limit of 3 fg mL(-1) (S/N=3). When applied to spiked serum samples, the recovery of the developed biosensor ranged from 100.8% to 101.4%, suggesting that the electrochemical biosensor would be suitable for the practical detection of alpha2,6-sialylated glycans. PMID- 26257189 TI - Getting the genome in shape: the formation of loops, domains and compartments. AB - The hierarchical levels of genome architecture exert transcriptional control by tuning the accessibility and proximity of genes and regulatory elements. Here, we review current insights into the trans-acting factors that enable the genome to flexibly adopt different functionally relevant conformations. PMID- 26257190 TI - TPX2 regulates neuronal morphology through kinesin-5 interaction. AB - TPX2 (targeting protein for Xklp2) is a multifunctional mitotic spindle assembly factor that in mammalian cells localizes and regulates mitotic motor protein kinesin-5 (also called Eg5 or kif11). We previously showed that upon depletion or inhibition of kinesin-5 in cultured neurons, microtubule movements increase, resulting in faster growing axons and thinner dendrites. Here, we show that depletion of TPX2 from cultured neurons speeds their rate of process outgrowth, similarly to kinesin-5 inhibition. The phenotype is rescued by TPX2 re expression, but not if TPX2's kinesin-5-interacting domain is deleted. These results, together with studies showing a spike in TPX2 expression during dendritic differentiation, suggest that the levels and distribution of TPX2 are likely to be determinants of when and where kinesin-5 acts in neurons. PMID- 26257192 TI - Mellow Parenting: systematic review and meta-analysis of an intervention to promote sensitive parenting. AB - AIM: To review and meta-analyse Mellow Parenting interventions for parent-child dyads at high risk of adverse developmental outcomes. METHOD: Using Preferred Reporting Items of Systematic reviews and Meta-Analyses (PRISMA) guidelines, we extracted all published evaluations of Mellow Parenting and Mellow Babies programmes. We identified published studies with randomized controlled trials, quasi-experimental or within-subject pre-post designs. We incorporated 'grey literature' for unpublished publicly available evaluations. Effect sizes were calculated for impact of Mellow Parenting on parental mental health and child behaviour. Data were extracted on demographics, age of participants, country, and potential sources of bias. RESULTS: We identified eight papers, representing nine data sets, from five of which we calculated effect sizes. There was evidence of a medium treatment effect of Mellow Parenting compared with comparison groups on maternal well-being and child problems. Drop-out from treatment was variable. However, data were heterogeneous and there was evidence of methodological bias. INTERPRETATION: Our data give some support to claims for effectiveness of Mellow Parenting as a group intervention for families with multiple indices of developmental adversity. Given the methodological weaknesses of literature in the area, novel approaches are needed in future trials of low-budget complex interventions in non-commercial settings. PMID- 26257193 TI - Experimental studies of adaptation in Clarkia xantiana. III. Phenotypic selection across a subspecies border. AB - Sister taxa with distinct phenotypes often occupy contrasting environments in parapatric ranges, yet we generally do not know whether trait divergence reflects spatially varying selection. We conducted a reciprocal transplant experiment to test whether selection favors "native phenotypes" in two subspecies of Clarkia xantiana (Onagraceae), an annual plant in California. For four quantitative traits that differ between subspecies, we estimated phenotypic selection in subspecies' exclusive ranges and their contact zone in two consecutive years. We predicted that in the arid, pollinator-scarce eastern region, selection favors phenotypes of the native subspecies parviflora: small leaves, slow leaf growth, early flowering, and diminutive flowers. In the wetter, pollinator-rich, western range of subspecies xantiana, we expected selection for opposite phenotypes. We investigated pollinator contributions to selection by comparing naturally pollinated and pollen-supplemented individuals. For reproductive traits and for subspecies xantiana, selection generally matched expectations. The contact zone sometimes showed distinctive selection, and in ssp. parviflora selection sometimes favored nonnative phenotypes. Pollinators influenced selection on flowering time but not on flower size. Little temporal variation in selection occurred, possibly because of plastic trait responses across years. Though there were exceptions and some causes of selection remain obscure, phenotypic differentiation between subspecies appears to reflect spatially variable selection. PMID- 26257191 TI - Vascular remodeling underlies rebleeding in hemophilic arthropathy. AB - Hemophilic arthropathy is a debilitating condition that can develop as a consequence of frequent joint bleeding despite adequate clotting factor replacement. The mechanisms leading to repeated spontaneous bleeding are unknown. We investigated synovial, vascular, stromal, and cartilage changes in response to a single induced hemarthrosis in the FVIII-deficient mouse. We found soft-tissue hyperproliferation with marked induction of neoangiogenesis and evolving abnormal vascular architecture. While soft-tissue changes were rapidly reversible, abnormal vascularity persisted for months and, surprisingly, was also seen in uninjured joints. Vascular changes in FVIII-deficient mice involved pronounced remodeling with expression of alpha-Smooth Muscle Actin (SMA), Endoglin (CD105), and vascular endothelial growth factor, as well as alterations of joint perfusion as determined by in vivo imaging. Vascular architecture changes and pronounced expression of alpha-SMA appeared unique to hemophilia, as these were not found in joint tissue obtained from mouse models of rheumatoid arthritis and osteoarthritis and from patients with the same conditions. Evidence that vascular changes in hemophilia were significantly associated with bleeding and joint deterioration was obtained prospectively by dynamic in vivo imaging with musculoskeletal ultrasound and power Doppler of 156 joints (elbows, knees, and ankles) in a cohort of 26 patients with hemophilia at baseline and during painful episodes. These observations support the hypothesis that vascular remodeling contributes significantly to bleed propagation and development of hemophilic arthropathy. Based on these findings, the development of molecular targets for angiogenesis inhibition may be considered in this disease. PMID- 26257194 TI - Late-onset recurrent mania as a manifestation of Wallenberg syndrome: a case report and review of the literature. AB - OBJECTIVE: The aim of the present case report was to describe the late onset of recurrent mania in a patient after ischemic injury to the cerebellum and dorsolateral medulla. METHODS: We studied an 86-year-old male with no prior psychiatric history who developed recurrent episodes of mania following a brain stroke. Additionally, he had neurological symptom constellation typical of Wallenberg syndrome. RESULTS: Magnetic resonance imaging of the brain revealed infarction in the inferomedial right cerebellar hemisphere and the right dorsolateral medulla in the right posterior inferior cerebellar artery (PICA) distribution. He was successfully managed with a combination of antipsychotic and mood-stabilizer medications. CONCLUSIONS: Post-stroke mania may be one of the rare manifestations of Wallenberg syndrome. This case adds to the emerging literature on cerebellar involvement in mood regulation and pathology of mania. PMID- 26257195 TI - Development of a functional assay to detect inhibitors of Plasmodium falciparum glutathione reductase utilizing liquid chromatography-mass spectrometry. AB - Plasmodium falciparum (Pf) like most other organisms, has a sophisticated antioxidant system, part of which includes glutathione reductase (GR). GR works by recycling toxic glutathione disulfide to glutathione, thereby reducing reactive oxygen species and making a form of glutathione (GSH) the parasite can use. Inhibition of this enzyme in Pf impedes parasite growth. In addition, it has been confirmed that PfGR is not identical to human GR. Thus, PfGR is an excellent target for antimalarial drug development. A functional assay utilizing liquid chromatography-mass spectrometry was developed to specifically identify and evaluate inhibitors of PfGR. Using recombinant PfGR enzyme and 1,4-naphthoquinone (1) as a reference compound and 4-nitrobenzothiadiazole (2) and methylene blue (3) as additional compounds, we quantified the concentration of GSH produced compared with a control to determine the inhibitory effect of these compounds. Our results coincide with that presented in literature: compounds 1-3 inhibit PfGR with IC50 values of 2.71, 8.38, and 19.23 um, respectively. Good precision for this assay was exhibited by low values of intraday and interday coefficient of variation (3.1 and 2.4%, respectively). Thus, this assay can be used to screen for other potential inhibitors of PfGR quickly and accurately. PMID- 26257196 TI - Glubran2(r), Histoacryl(r) or Trufill(r): Which cyanoacrylate glue for endovascular use? PMID- 26257197 TI - Separation and on-line preconcentration of nonsteroidal anti-inflammatory drugs by microemulsion electrokinetic chromatography. AB - The MEEKC separation and on-line preconcentration of nonsteroidal anti inflammatory drugs (NSAIDs) were investigated. In this work, two microemulsion (ME) systems were employed. Complete separation could be achieved at a pH of 5.5 with octane as the oil phase (ME I). The LODs for the determination of flurbiprofen, fenoprofen, naproxen, ketoprofen, suprofen, and indoprofen were 0.45, 0.32, 0.10, 0.48, 0.77, and 0.29 mg/L, respectively. To enhance the sensitivity, anion selective exhaustive injection-sweeping (ASEI-sweeping) and stacking with reverse migrating pseudostationary phase (SRMP) were compared. For having a simple process without polarity switching and shorter analysis time, a suppressed EOF and di-n-butyl-L-tartrate as the oil phase (ME II) were used for the simultaneous determination of NSAIDs. The sensitivity for ASEI-sweeping was enhanced approximately 280-fold. However, there was much background noise, and some of the analytes were co-eluted. When SRMP was used, all of the analytes could be detected simultaneously, and baseline separation could be achieved. The sensitivities of all of the analytes, except for indoprofen, were enhanced approximately 170-fold compared with the normal MEEKC, and the LODs were 2-45 MUg/L. Herein, we propose a simple method for the direct determination of NSAIDs at therapeutic and toxic levels in urine throughout a wide concentration range. PMID- 26257199 TI - cAMP controls the balance of the propulsive forces generated by the two flagella of Chlamydomonas. AB - The motility of cilia and flagella of eukaryotic cells is controlled by second messengers such as Ca(2+), cAMP, and cGMP. In this study, the cAMP-dependent control of flagellar bending of Chlamydomonas is investigated by applying cAMP through photolysis of 4,5-dimethoxy-2-nitrobenzyl adenosine 3',5' cyclicmonophosphate (caged cAMP). When cAMP is applied to demembranated and reactivated cells, cells begin to swim with a larger helical path. This change is due to a larger turn about the axis normal to the anterior-posterior axis, indicating an increased imbalance in the propulsive forces generated by the cis flagellum (flagellum nearer to the eyespot) and trans-flagellum (flagellum farther from the eyespot). Consistently, when cAMP is applied to isolated axonemes, some axonemes show attenuated motility whereas others do not. Axonemes from uni1 mutants, which have only trans-flagella, do not respond to cAMP. These observations indicate that cAMP controls the balance of the forces generated by cis- and trans-flagella in Chlamydomonas. PMID- 26257198 TI - Pathophysiology of cutaneous lupus erythematosus. AB - The pathophysiology of cutaneous lupus erythematosus (CLE) encompasses the complex interactions between genetics, the environment, and cells and their products. Recent data have provided enhanced understanding of these interactions and the mechanism by which they cause disease. A number of candidate genes have been identified which increase the risk of developing CLE. Ultraviolet radiation, the predominant environmental exposure associated with CLE, appears to initiate CLE lesion formation by inducing apoptosis, precipitating autoantigen presentation, and promoting cellular production of specific cytokines. Autoantibodies are a well-known entity in CLE, but their exact role remains unclear. Finally, cells ranging from native skin cells to innate and adaptive immune cells produce cytokines and other molecules and play specific roles in lesion formation and perpetuation. Native skin cells implicated in CLE include keratinocytes and endothelial cells. Innate immune cells crucial to CLE pathophysiology include dendritic cells and neutrophils. The primary adaptive immune cells thought to be involved include Th1 cells, Th17 cells, cytotoxic T cells, and invariant natural killer T cells. Though the pathophysiology of CLE has yet to be fully characterized, current research provides direction for future research and therapies. PMID- 26257200 TI - The quest for patterns in dyskinetic cerebral palsy. PMID- 26257201 TI - Critical Reviews: How we treat sickle cell patients with leg ulcers. AB - The past five decades have seen an improvement in the mortality and morbidity of sickle cell disease (SCD) because of prophylaxis against infectious complications, improved and expanded red cell transfusions, implementation of hydroxyurea therapy, and advances in supportive care. Now that the majority of patients in the western hemisphere reaches adulthood, end organ diseases are frequent, which include vasculopathic complications such as chronic leg ulcers. The management of patients with leg ulcers requires the hematologist to lead a team of health care professionals, and investigates the presence of associated, but potentially still occult signs of vasculopathy, such as pulmonary hypertension, renal disease, priapism and retinopathy. These complications may be asynchronous, and long term careful screening is indicated, in order to ensure early diagnosis and intervention. It is crucial to address both the immediate consequences of pain, infection and disability, and long term effects on quality of life, employment and stigma associated with chronic ulceration. Recent insights into their pathophysiology may have practical implications. We propose a holistic approach to the management of patients' physical and emotional problems and mechanisms of ulcers formation and delayed healing. An overview of topical and systemic therapies for chronic ulcers is given, with the understanding that wound care therapy is best left to the wound specialists, medical and surgical, with whom the hematologist must keep an open line of communication. In the absence of evidence-based guidelines, our opinion is based on both a critical review of the literature and our personal clinical and research experience. PMID- 26257202 TI - Morphological innovation, ecological opportunity, and the radiation of a major vascular epiphyte lineage. AB - The emergence of angiosperm-dominated tropical forests in the Cretaceous led to major shifts in the composition of biodiversity on Earth. Among these was the rise to prominence of epiphytic plant lineages, which today comprise an estimated one-quarter of tropical vascular plant diversity. Among the most successful epiphytic groups is the Polypodiaceae, which comprises an estimated 1500 species and displays a remarkable breadth of morphological and ecological diversity. Using a time-calibrated phylogeny for 417 species, we characterized macroevolutionary patterns in the family, identified shifts in diversification rate, and identified traits that are potential drivers of diversification. We find high diversification rates throughout the family, evidence for a radiation in a large clade of Paleotropical species, and support for increased rates of diversification associated with traits including chlorophyllous spores and noncordiform gametophytes. Contrary to previous hypotheses, our results indicate epiphytic species and groups with humus-collecting leaves diversify at lower rates than the family as a whole. We find that diversification rates in the Polypodiaceae are positively correlated with changes in elevation. Repeated successful exploration of novel habitat types, rather than morphological innovation, appears to be the primary driver of diversification in this group. PMID- 26257203 TI - Abnormal gene expression of proinflammatory cytokines and their receptors in the lymphocytes of patients with bipolar disorder. AB - OBJECTIVES: Abnormalities of protein levels of proinflammatory cytokines and their soluble receptors have been reported in plasma of patients with bipolar disorder (BP). In this study, we tested the hypothesis that the mRNA expression of membrane-bound receptors for proinflammatory cytokines will be altered in the lymphocytes of patients with BP. METHODS: We determined protein and mRNA expression of proinflammatory cytokines, and mRNA expression of their receptors in the lymphocytes from 29 drug-free, hospitalized patients with BP and 30 drug free normal control subjects. The subjects were diagnosed according to DSM-IV criteria. Plasma protein levels of cytokines were determined by enzyme-linked immunosorbent assay (ELISA); mRNA levels in lymphocytes were determined by the quantitative polymerase chain reaction (qPCR) method. RESULTS: We found that mean mRNA levels of the proinflammatory cytokines interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha, and their receptors TNFR1, IL-1R1, and the antagonist IL-1RA were significantly higher in the lymphocytes of patients with BP compared with normal controls. CONCLUSIONS: This study suggests that the observed abnormalities of membrane-bound cytokine receptors may alter the functional response of cytokines in BP and that the mRNA levels of these receptors could be a potential biomarker. PMID- 26257204 TI - CD4 changes among virologically suppressed patients on antiretroviral therapy: a systematic review and meta-analysis. AB - INTRODUCTION: The effectiveness of antiretroviral therapy (ART) is assessed by measuring CD4 cell counts and viral load. Recent studies have questioned the added value of routine CD4 cell count measures in patients who are virologically suppressed. METHODS: We systematically searched three databases and two conference sites up to 31 October 2014 for studies reporting CD4 changes among patients who were on ART and virologically suppressed. No geographic, language or age restrictions were applied. RESULTS AND DISCUSSION: We identified 12 published and 1 unpublished study reporting CD4 changes among 20,297 virologically suppressed patients. The pooled proportion of patients who experienced an unexplained, confirmed CD4 decline was 0.4% (95% CI 0.2-0.6%). Results were not influenced by duration of follow-up, age, study design or region of economic development. No studies described clinical adverse events among virologically suppressed patients who experienced CD4 declines. CONCLUSIONS: The findings of this review support reducing or stopping routine CD4 monitoring for patients who are immunologically stable on ART in settings where routine viral load monitoring is provided. PMID- 26257205 TI - High-throughput T-cell receptor sequencing across chronic liver diseases reveals distinct disease-associated repertoires. AB - Hepatic T-cell infiltrates and a strong genetic human leukocyte antigen association represent characteristic features of various immune-mediated liver diseases. Conceptually the presence of disease-associated antigens is predicted to be reflected in T-cell receptor (TCR) repertoires. Here, we aimed to determine if disease-associated TCRs could be identified in the nonviral chronic liver diseases primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and alcoholic liver disease (ALD). We performed high-throughput sequencing of the TCRbeta chain complementarity-determining region 3 of liver-infiltrating T cells from PSC (n = 20), PBC (n = 10), and ALD (n = 10) patients, alongside genomic human leukocyte antigen typing. The frequency of TCRbeta nucleotide sequences was significantly higher in PSC samples (2.53 +/- 0.80, mean +/- standard error of the mean) compared to PBC samples (1.13 +/- 0.17, P < 0.0001) and ALD samples (0.62 +/- 0.10, P < 0.0001). An average clonotype overlap of 0.85% was detected among PSC samples, significantly higher compared to the average overlap of 0.77% seen within the PBC (P = 0.024) and ALD groups (0.40%, P < 0.0001). From eight to 42 clonotypes were uniquely detected in each of the three disease groups (>=30% of the respective patient samples). Multiple, unique sequences using different variable family genes encoded the same amino acid clonotypes, providing additional support for antigen-driven selection. In PSC and PBC, disease associated clonotypes were detected among patients with human leukocyte antigen susceptibility alleles. CONCLUSION: We demonstrate liver-infiltrating disease associated clonotypes in all three diseases evaluated, and evidence for antigen driven clonal expansions. Our findings indicate that differential TCR signatures, as determined by high-throughput sequencing, may represent an imprint of distinctive antigenic repertoires present in the different chronic liver diseases; this thereby opens up the prospect of studying disease-relevant T cells in order to better understand and treat liver disease. PMID- 26257206 TI - Roles of EGFR and KRAS and their downstream signaling pathways in pancreatic cancer and pancreatic cancer stem cells. AB - Pancreatic cancer is currently the fourth most common cancer, is increasing in incidence and soon will be the second leading cause of cancer death in the USA. This is a deadly malignancy with an incidence that approximates the mortality with 44,000 new cases and 36,000 deaths each year. Surgery, although only modestly successful, is the only curative option. However, due the locally aggressive nature and early metastasis, surgery can be performed on less than 20% of patients. Cytotoxic chemotherapy is palliative, has significant toxicity and improves survival very little. Thus new treatment paradigms are needed desperately. Due to the extremely high frequency of KRAS gene mutations (>90%) detected in pancreatic cancer patients, the roles of the epidermal growth factor receptor (EGFR), Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTORC1/GSK-3 pathways have been investigated in pancreatic cancer for many years. Constitutively active Ras can activate both of these pathways and there is cross talk between Ras and EGFR which is believed to be important in driving metastasis. Mutant KRAS may also drive the expression of GSK-3 through Raf/MEK/ERK-mediated effects on GSK-3 transcription. GSK-3 can then regulate the expression of NF-kappaB which is important in modulating pancreatic cancer chemoresistance. While the receptors and many downstream signaling molecules have been identified and characterized, there is still much to learn about these pathways and how their deregulation can lead to cancer. Multiple inhibitors to EGFR, PI3K, mTOR, GSK-3, Raf, MEK and hedgehog (HH) have been developed and are being evaluated in various cancers. Current research often focuses on the role of these pathways in cancer stem cells (CSC), with the goal to identify sites where therapeutic resistance may develop. Relatively novel fields of investigation such as microRNAs and drugs used for other diseases e.g., diabetes, (metformin) and malaria (chloroquine) have provided new information about therapeutic resistance and CSCs. This review will focus on recent advances in the field and how they affect pancreatic cancer research and treatment. PMID- 26257208 TI - Investigation of photochemical reaction products of glucose formed during direct UV detection in CE. AB - In CE, saccharides are accessible to direct UV detection due to a photochemical reaction in the detection window of the separation capillary resulting in the formation of UV absorbing substances. Employing a CE method that allows long in capillary irradiation with subsequent UV and MS detection, the present study could identify several reaction products of glucose. Among these were UV absorbing substances so far unknown to be formed during direct UV detection with the chemical formulas C4 H6 O2 , C5 H6 O4 , C5 H8 O3, and C6 H8 O5 . Investigations of the impact of the irradiation time revealed differences between these reaction products suggesting differing reaction mechanisms especially for the smallest products. More detailed information could be obtained by experiments with isotope-labeled substrates performed to determine the parts of glucose that are converted to the particular reaction products. In addition, structural formulas for the reaction products were suggested based on HPLC-MS/MS measurements of off-line irradiated glucose solutions which revealed the existence of functional groups such as carboxylic acid or aldehyde groups. PMID- 26257207 TI - Targeting executioner procaspase-3 with the procaspase-activating compound B-PAC 1 induces apoptosis in multiple myeloma cells. AB - Multiple myeloma (MM) is a plasma cell neoplasm that has a low apoptotic index. We investigated a new class of small molecules that target the terminal apoptosis pathway, called procaspase activating compounds (PACs), in myeloma cells. PAC agents (PAC-1 and B-PAC-1) convert executioner procaspases (procaspase 3, 6, and 7) to active caspases 3, 6, and 7, which cleave target substrates to induce cellular apoptosis cascade. We hypothesized that targeting this terminal step could overcome survival and drug-resistance signals in myeloma cells and induce programmed cell death. Myeloma cells expressed executioner caspases. Additionally, our studies demonstrated that B-PAC-1 is cytotoxic to chemotherapy resistant or sensitive myeloma cell lines (n = 7) and primary patient cells (n = 11). Exogenous zinc abrogated B-PAC-1-induced cell demise. Apoptosis induced by B PAC-1 treatment was similar in the presence or absence of growth-promoting cytokines such as interleukin 6 and hepatocyte growth factor. Presence or absence of antiapoptotic proteins such as BCL-2, BCL-XL, or MCL-1 did not impact B-PAC-1 mediated programmed cell death. Collectively, our data demonstrate the proapoptotic effect of B-PAC-1 in MM and suggest that activating terminal executioner procaspases 3, 6, and 7 bypasses survival and drug-resistance signals in myeloma cells. This novel strategy has the potential to become an effective antimyeloma therapy. PMID- 26257209 TI - A Brief Mindfulness Meditation Training Increases Pain Threshold and Accelerates Modulation of Response to Tonic Pain in an Experimental Study. AB - OBJECTIVE: Research shows that mindfulness meditation (MM) affects pain perception; however, studies have yet to measure patterns of change over time. We examined effects of MM on perception of experimental heat pain using multiple psychophysical indices, including pattern of change in response to tonic painful stimuli. We also tested the potential moderating role of baseline mindfulness. METHOD: Forty participants were randomly assigned to a brief MM training or control group. We assessed: a) heat pain threshold (HPT), b) temperature which induces pain at a fixed, target intensity level, and c) response pattern over time to tonic heat pain. RESULTS: Compared to control group, the MM group showed increased HPT and more rapid attenuation of pain intensity for tonic pain stimuli. Moderation analyses indicated that baseline mindfulness moderated effects of MM on HPT. CONCLUSIONS: A brief MM intervention appears to affect perception of experimental pain both by increasing pain threshold and accelerating modulation of response. Findings may help elucidate mechanisms of MM for chronic pain. PMID- 26257211 TI - Efficient extraction of proteins from recalcitrant plant tissue for subsequent analysis by two-dimensional gel electrophoresis. AB - Protein extraction for two-dimensional electrophoresis from tissues of recalcitrant species is quite problematic and challenging due to the low protein content and high abundance of contaminants. Proteomics in Shorea robusta is scarcely conducted due to the lack of a suitable protein preparation procedure. To establish an effective protein extraction protocol suitable for two dimensional electrophoresis in Shorea robusta, four procedures (borate buffer/trichloroacetic acid extraction, organic solvent/trichloroacetic acid precipitation, sucrose/Tris/phenol, and organic solvent/phenol/sodium dodecyl sulfate) were evaluated. Following these, proteins were isolated from mature leaves and were analyzed for proteomics, and also for potential contaminants, widely reported to hinder proteomics. The borate buffer/trichloroacetic acid extraction had the lowest protein yield and did not result in any banding even in one-dimensional electrophoresis. In contrast, organic solvent/phenol/sodium dodecyl sulfate extraction allowed the highest protein yield. Moreover, during proteomics, organic solvent/phenol/sodium dodecyl sulfate extracted protein resolved the maximum number (144) of spots. Further, when proteins were evaluated for contaminants, significant (77-95%) reductions in the nucleic acids, phenol, and sugars were discernible with refinement in extraction procedure. Accumulated data suggested that the organic solvent/phenol/sodium dodecyl sulfate extraction was the most effective protocol for protein isolation for proteomics of Shorea robusta and can be used for plants that have a similar set of contaminants. PMID- 26257210 TI - FACTORS ASSOCIATED WITH THE LIKELIHOOD OF FURTHER MOVEMENT AMONG MOBILE FEMALE SEX WORKERS IN INDIA: A MULTINOMIAL LOGIT APPROACH. AB - Female sex workers (FSWs) are vulnerable to HIV infection. Their socioeconomic and behavioural vulnerabilities are crucial push factors for movement for sex work. This paper assesses the factors associated with the likelihood of movement of sex workers from their current place of work. Data were derived from a cross sectional survey conducted among 5498 mobile FSWs in 22 districts of high in migration across four states in southern India. A multinomial logit model was constructed to predict the likelihood of FSWs moving from their current place of work. Ten per cent of the sampled mobile FSWs were planning to move from their current place of sex work. Educational attainment, marital status, income at current place of work, debt, sexual coercion, experience of violence and having tested for HIV and collected the results were found to be significant predictors of the likelihood of movement from the current place of work. Consistent condom use with different clients was significantly low among those planning to move. Likewise, the likelihood of movement was significantly higher among those who had any STI symptom in the last six months and those who had a high self-perceived risk of HIV. The findings highlight the need to address factors associated with movement among mobile FSWs as part of HIV prevention and access to care interventions. PMID- 26257212 TI - t(9;22) as secondary alteration in core-binding factor de novo acute myeloid leukemia. PMID- 26257213 TI - Application of RDC enhanced NMR spectroscopy in structural analysis of thiacalix[4]arene derivatives. AB - Thiacalix[4]arene spirodienone was rearranged into the corresponding phenoxathiin based macrocycle. Alkylation of this inherently chiral system to achieve its immobilization led to a mixture of only two (out of four theoretically possible) stereoisomers. As standard NOE and dynamic NMR experiments did not lead to unambiguous determination of the structures we applied the Residual Dipolar Coupling constant (RDC) method. Poly-gamma-ethyl-l-glutamate (PELG) and poly gamma-benzyl-l-glutamate (PBLG) were found to be easily applicable lyotropic liquid crystalline alignment media for the conformational analysis of thiacalixarene derivatives. Using these media the 1,2-alternate and the partial cone conformations were determined unequivocally. PMID- 26257214 TI - Re: Radiation for Prostate Cancer: Intensity Modulated Radiation Therapy versus Proton Beam: B. S. Hoppe, C. Bryant and H. M. Sandler J Urol 2015;193:1089-1091. PMID- 26257215 TI - An ophthalmology code of ethics in Canada: enhancing our practice patterns. PMID- 26257217 TI - The 20/20 patient who can't read. AB - To understand how reading can be disrupted in patients with good acuity, it is important to realize the complexities that underlie this task, which normally seems so effortless. The process of reading is an interplay among vision, eye movements, attention, and linguistic processing, and impairments in any of these functions can result in reduced reading efficiency. The goal of this review is to provide a systematic review of these functions that can help clinicians generate a logical and useful differential diagnosis of impaired reading in the patient with 20/20 vision. PMID- 26257218 TI - Value of subjective visual reduction in patients with acute-onset floaters and/or flashes. AB - OBJECTIVE: To quantify the association between subjective visual reduction (SVR) and retinal pathology in patients with acute-onset monocular floaters or flashes, or both. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohorts study involving all new patients referred for acute-onset floaters or flashes, or both, to a tertiary care emergency eye clinic in Kingston, Ontario, between July 1, 2011, and June 29, 2012 (n = 333). METHODS: All patients were evaluated for the presence of SVR in a standardized fashion, as well as other known risk factors for retina pathology including a family history of retinal tear or retinal detachment, a personal history of retinal tear or detachment, high myopia, and ocular trauma. Our major outcome was urgent retinal pathology, defined as retina pathology requiring a same-day referral to a retina specialist for evaluation, management, or both. RESULTS: SVR was strongly associated with retinal pathology (likelihood ratio 7.9, 95% CI 5.2-12.1). CONCLUSIONS: Patients with SVR are at increased risk for urgent retinal pathology and should be triaged for urgent ophthalmologic examination. PMID- 26257219 TI - Fibrin glue versus autologous blood for conjunctival autograft fixation in pterygium surgery. AB - OBJECTIVE: To compare the outcomes between autologous blood- and fibrin glue fixated conjunctival autografts in pterygium excision surgery. DESIGN: Retrospective case series. PARTICIPANTS: Forty eyes of 40 patients who had a primary nasal pterygium excision. METHODS: A retrospective comparative case series of 40 eyes (40 patients) that had a primary nasal pterygium excision. All eyes had a conjunctival autograft from the superior bulbar conjunctiva to cover the scleral bed. Twenty eyes (20 patients) had fixation of the autograft using autologous blood (AB), and 20 eyes (20 patients) had fixation using fibrin glue (FG). One year of follow-up data included conjunctival graft stability (graft loss, graft retraction), pterygium recurrence, visual acuity, and postoperative complications. Descriptive and inferential statistics were performed. RESULTS: Intraoperatively, no complications occurred in either group. Graft loss occurred in 6 patients in the AB group, compared with none in the FG group. Graft retraction occurred in 3 patients in the AB group and 2 patients in the FG group. At 1 year postoperatively, pterygium recurrence occurred in 4 patients in the AB group and 1 patient in the FG group. One patient in the AB group developed a small pyogenic granuloma that resolved by 6 months with conservative management. Visual acuity remained stable in both groups. CONCLUSIONS: Conjunctival autograft fixation with autologous blood resulted in less stable conjunctival autografts and a higher recurrence rate compared with fixation with fibrin glue. PMID- 26257220 TI - Comparison of conjunctival staining between lissamine green and yellow filtered fluorescein sodium. AB - OBJECTIVE: To compare conjunctival staining between lissamine green and fluorescein sodium using a yellow barrier filter. DESIGN: Retrospective cross sectional study. PARTICIPANTS: Thirteen eyes of 13 patients with dry eyes. METHODS: All patients underwent ocular surface staining with fluorescein sodium and lissamine green. Ocular surface staining with fluorescein sodium was observed through slit-lamp examination under cobalt blue illumination and a yellow filter. Temporal (0-5) and nasal (0-5) conjunctival staining grade was separately graded according to the Oxford scheme. The contrast score was defined as the absolute difference between mean grey values of punctate staining and background. Conjunctival staining grade and contrast scores were compared between these 2 staining methods. RESULTS: The sum of the conjunctival staining grade (0-10) for the nasal and temporal conjunctiva was 4.7 +/- 2.5 for fluorescein sodium, which was significantly higher than that of lissamine green, 4.1 +/- 2.5 (p = 0.005). The contrast score of temporal and nasal conjunctival staining was 34.6 +/- 12.0 and 34.7 +/- 10.3, respectively, for fluorescein sodium, which was also significantly greater than for lissamine green (23.4 +/- 8.1 and 21.0 +/- 9.0, respectively; p = 0.003 and p = 0.003, respectively). CONCLUSIONS: Conjunctival staining with fluorescein sodium and a yellow filter seems to be more sensitive for the detection of conjunctival damage than lissamine green. Fluorescein staining with the yellow filter has the advantage of simultaneous observation of both corneal and conjunctival damage in patients with dry eye without the need for additional vital staining. PMID- 26257221 TI - Meibomian gland dysfunction in Graves' orbitopathy. AB - OBJECTIVE: To examine morphologic changes in the meibomian glands associated with patients with Graves' orbitopathy (GO) using a novel meibography imaging system, and to evaluate its correlation with GO clinical manifestations. DESIGN: Retrospective, observational case series. PARTICIPANTS: Fifty-one GO patients and 31 normal control participants. METHODS: This retrospective study examined 51 GO patients and 31 normal control participants. The structure of the meibomian gland was assessed using the meibography imaging system. All of the participants completed the Ocular Surface Disease Index (OSDI) questionnaire. The tear film break-up time (BUT) was measured. The palpebral fissure height, exophthalmos, and eyelid retraction were also assessed. RESULTS: The meibography score, tear film BUT, and OSDI indicated statistically significant differences between the GO and normal groups: The tear film BUT was shorter and the OSDI and meibography score were higher in the GO patient group. There was a significant negative correlation between the meibography score and the tear film BUT in GO patients (r = -.503 and p < .001). In the multivariable linear regression analysis, the meibography score of the GO patients had a positive association with exophthalmos and palpebral fissure height. CONCLUSIONS: Compared with the normal control participants, GO patients had more unstable tear films and severe symptoms of dry eye. Using the meibography system, the authors found that GO patients had a higher prevalence of obstructive type meibomian gland dysfunction and changes in meibomian glands increased, with proptosis and lid fissure widening. PMID- 26257222 TI - Effects of osmoprotective eye drops on tear osmolarity in contact lens wearers. AB - OBJECTIVE: To evaluate the impact of osmoprotective eye drops on tear osmolarity and patient comfort, and to compare its efficacy with a commercially available lubricant in contact lens (CL) wearers. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: Forty eyes of 20 first-time CL wearers were included. METHODS: Tear osmolarity measurements using TearLab osmolarity system were performed in each eye of subjects at 8 am, and 2, 4, and 8 h after that on the first and second days, and at 12:00 on the third day and eighth days. On the second day and afterward, all eyes were fitted Purevision 2 (Bausch & Lomb) soft CLs. Subjects instilled Optive (Allergan) osmoprotective eye drops into their 1 eye (group 1) and Refresh tears (Allergan) eye drops into their other eyes (group 2) after 2 hours of CL wear on the third day and afterward. Ocular comfort with eye drops was also assessed. RESULTS: There were no significant differences between the tear osmolarity measurements of the groups on the first day. On the second day, osmolarity significantly increased from baseline after 4 h of CL wear (p < 0.05) but returned to baseline after 8 h of CL wear (p > 0.05) in both groups. Tear osmolarity measurements of group 1 were significantly lower than those of group 2 on the third and eighth days (both p < 0.05). The mean comfort scores were significantly higher in group 1. CONCLUSIONS: Tear osmolarity increases within the first hours of CL wear, and instillation of osmoprotective eye drops prevents this increment in patients wearing CLs. PMID- 26257223 TI - Flicker defined form, standard perimetry and Heidelberg retinal tomography: Structure-function relationships. AB - OBJECTIVE: To compare flicker defined form (FDF) perimetry using the Heidelberg edge perimeter (HEP) with standard automated perimetry (SAP) on the Humphrey visual field (HVF) analyzer and to compare their relationship to structural measurements acquired with the Heidelberg retina tomograph. DESIGN: Prospective, observational study. PARTICIPANTS: Thirty-one glaucomatous eyes with varying severity and 13 normal control eyes were included in this analysis. METHODS: All subjects underwent FDF testing on the HEP using the 24-2 protocol by the adaptive staircase thresholding algorithm standard strategy and SAP on the HVF analyzer 750 II using the SITA-Standard 24-2 test. Heidelberg retina tomography (HRT) testing was obtained for each patient. Spearman correlation coefficient, mean deviation (MD), and pattern standard deviation measurements by both machines were compared. RESULTS: FDF and SAP MD were significantly correlated (r = 0.81, p < 0.001). FDF and SAP MD were significantly correlated with HRT cup/disc ratio (FDF MD: p < 0.001; SAP MD: p = 0.003), disc area (FDF MD: p = 0.005; SAP MD: p = 0.059), rim volume (FDF MD: p < 0.001; SAP MD: p < 0.001), and retinal nerve fibre layer (FDF MD: p < 0.001; SAP MD: p < 0.001). CONCLUSIONS: This pilot study shows that the MD parameter of FDF correlated with SAP results. FDF and SAP had significant correlations with HRT parameters in glaucomatous and healthy eyes. The potential utility of FDF in the clinical management of glaucoma requires further investigation. PMID- 26257224 TI - Carbonic anhydrase inhibitors as fourth drug in primary glaucomas: Is it worth it? AB - OBJECTIVE: To evaluate the effectiveness of carbonic anhydrase inhibitors as the fourth drug regarding intraocular pressure (IOP) control in patients with primary glaucomas. DESIGN: Single-centre, prospective study. PARTICIPANTS: Twenty-five eyes from 25 patients with primary glaucomas treated concomitantly with a topical prostaglandin analogue, a beta-blocker, an alpha-adrenergic agonist, and a carbonic anhydrase inhibitor. METHODS: Patients followed at the Federal University of Sao Paulo were enrolled from August to November 2013 and were initially submitted to an ophthalmologic examination where the IOP was measured at 8 am, 10 am, and 12 pm. Afterward, patients underwent a 15-day washout of the carbonic anhydrase inhibitor and had their IOP measured again. RESULTS: Most patients were female, white, and with a mean age of 66.4 +/- 9.7 years. The removal of the fourth drug had a statistically significant effect on the IOP peak (increase of 1.20 mm Hg, p < 0.01) and mean (increase of 1.23 mm Hg, p < 0.01), but it did not interfere significantly with morning fluctuation of the IOP (p = 0.83). After discontinuation of the fourth drug, the IOP increased >=2 mm Hg in 32% of the patients, and there was a significant increase of the IOP (defined as an IOP change >=20%) in only 5 patients (20%). Age older than 60 years was associated with 20% of the documented IOP change (R(2) = 0.19, p = 0.03). CONCLUSIONS: The removal of a fourth medication does not appear to have a clinically significant impact on IOP control in most patients with glaucoma. However, 32% of the patients experienced an IOP increase >=2 mm Hg, with age older than 60 years being the only significant predictive factor. PMID- 26257225 TI - Fixation characteristics among subjects with diabetes: SN-DREAMS II, Report No. 5. AB - OBJECTIVE: To evaluate fixation and scotoma characteristics among subjects with diabetes in a population-based study. DESIGN: Cohort study. PARTICIPANTS: A subset of 357 subjects was recruited from follow-up cohort of Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study I. METHODS: All subjects underwent detailed ophthalmic evaluation including microperimetry and spectral domain optical coherence tomography. Fixation parameters such as stability of fixation, fixation location, and presence of scotoma were evaluated. A p value less than 0.05 was considered statistically significant. RESULTS: The mean age of the study sample was 56.86 +/- 8.63 years. Relatively unstable fixation was observed in 73 and poor central fixation in 25 subjects. Among subjects with poor central fixation, 72% (18 subjects) had relatively unstable fixation. Poor central and relatively unstable fixation were significantly associated with best corrected visual acuity (BCVA; p = 0.002 and p = 0.017, respectively). Prevalence rate of scotoma was 24.4%, which was highly prevalent in females (p = 0.035) and among subjects with reduced BCVA (p < 0.001), reduced contrast sensitivity (p < 0.001), cataract (p < 0.001), impaired retinal sensitivity (p < 0.001), and presence of sight-threatening diabetic retinopathy (STDR; p < 0.001). Presence of scotoma was significantly associated with abnormal foveal contour (p = 0.046) and altered inner retinal layers (p < 0.001). CONCLUSIONS: We report that fixation characteristics are independent of ocular characteristics except for BCVA. Female sex, reduced visual acuity and contrast sensitivity, cataract, and STDR were significantly associated with presence of scotoma. PMID- 26257226 TI - Duane syndrome: Clinical features and surgical management. AB - OBJECTIVE: To further define the clinical features of Duane syndrome and analyze the surgical outcomes in a subset of these patients. DESIGN: Retrospective chart review. PARTICIPANTS: A retrospective chart review of 75 patients with Duane syndrome was performed. METHODS: Complete ophthalmologic and orthoptic data were extracted from the patients' charts, and patients were classified into group I, II, or III based on forced primary position (PP) deviation. Eighteen patients had strabismus surgery to correct the ocular misalignment with its related abnormal head posture. RESULTS: Fifty-six percent of the cases were in group I, 16% in group II, and 28% in group III. Fifty-seven percent were female, 91% were unilateral, and 66% had left eye involvement. Ninety-six percent had fissure narrowing/globe retraction on adduction; 67% had an upshoot, downshoot, or both; and 63% had an A, V, or X pattern. The A patterns correlated with downshoots in 100% of cases, V patterns with upshoots in 88%, and X patterns with upshoots/downshoots in 100%. In the 18 surgical candidates, there were 14 patients in group I, 4 in group II, and 0 in group III. An excellent surgical outcome occurred in 78% of patients and a fair-to-poor outcome in 22%. Upshoots/downshoots and fissure-narrowing/globe retraction patients showed modest improvement after surgery. CONCLUSIONS: There was a consistent relationship among the type of strabismus, head position, and motility defect. The type of upshoot/downshoot correlated strongly with the A, V, or X pattern. Postoperative improvements of abnormal head posture and PP alignment were achieved in the surgical subset of patients. PMID- 26257227 TI - Prognostic value of metal-metal contact during nasolacrimal duct probing. AB - OBJECTIVE: To evaluate the prognostic value of metal-metal contact during nasolacrimal duct (NLD) probing in patients with simple membranous versus complex congenital NLD obstructions (CNLDO). DESIGN: Retrospective case series. PARTICIPANTS: Infants diagnosed with CNLDO. METHODS: Seventy-nine eyes of 70 infants with CNLDO who underwent probing were recruited. Metal-metal contact was sought during probing in every patient. CNLDO was classified into simple membranous versus complex type of obstruction. Complete resolution of epiphora, increased tear meniscus, and mucous discharge were defined as successful outcome. RESULTS: The mean age of patients at the time of probing was 21.0 +/- 8.3 (range 1-42) months. Postoperative evaluations were performed in all patients between the first and second postoperative months. Overall success rate of probing was 84.9%. A higher success rate was obtained in membranous (89.7%) versus complex (54.5%) obstructions (p = 0.01). A metal-metal contact could be established in 62 (78.5%) eyes. Treatment success was achieved in 93.5% of cases in which metal metal contact was detected versus 52.9% of cases without metal-metal contact (p < 0.001). Among cases with metal-metal contact, a trend toward successful outcomes was observed with membranous as compared with complex obstructions (96.4% vs 71.4%, p = 0.059). Logistic regression analysis revealed the presence of metal metal touch (odds ratio [OR] 13.3, p = 0.001) and membranous type obstruction (OR 7.7, p = 0.019) as significant factors for a successful outcome. CONCLUSIONS: Establishment of metal-metal contact is an important prognostic sign for surgical success in both the membranous and the complex type of CNLDO. PMID- 26257228 TI - Traumatic carotid cavernous fistula in a pediatric patient. PMID- 26257229 TI - Histopathologic findings of perforated corneas due to ferric ion infiltration. AB - OBJECTIVE: To report the histopathologic findings of 3 corneal buttons incised from 2 patients during penetrating keratoplasty (PKP) because of corneal perforation due to corneal siderosis. METHODS: Three eyes of 2 patients had accidental trauma to the corneas caused by iron fragments; the injuries were initially treated conservatively with antibiotics and therapeutic soft contact lenses. However, the corneal stroma melted and perforated, necessitating corneal transplantation. The corneal buttons removed during PKP were examined histopathologically, and the findings were compared with the slit-lamp biomicroscopic and anterior segment optical coherence tomographic (AS-OCT) findings. RESULTS: Slit-lamp examinations showed that the corneal epithelium was hyperplasic around the area of perforation in 2 eyes 1 month after the injury. Wide areas of the stroma had melted, and the corneas were perforated. The corneal epithelium was atrophic in the perforated corneas 4 months after injury. Histopathologically, the corneal stroma and Descemet's membrane were stained by Prussian blue, suggesting that the ferric ions had penetrated deeper than expected by the slit-lamp examinations. The areas of Prussian blue staining corresponded well with the areas altered in the AS-OCT images. CONCLUSIONS: Ferric ions penetrate much deeper into the cornea than estimated by slit-lamp biomicroscopy. The ferric ions can induce stromal melting that can lead to corneal perforation. We conclude that (i) the ferric ion-infiltrated areas can be estimated in the AS-OCT images and (ii) extensive corneal abrasion should be performed to prevent corneal melting and perforation. PMID- 26257230 TI - Ophthalmia neonatorum prophylaxis. PMID- 26257231 TI - National cross-sectional study of Canadian ophthalmology residency participation in external courses. PMID- 26257232 TI - Asymptomatic bacteriuria and acute-onset endophthalmitis after cataract surgery. PMID- 26257233 TI - Bilateral reversible macular edema following road traffic collision. PMID- 26257234 TI - Corneal stromal damage through the eyelid after tightening using intense focused ultrasound. PMID- 26257235 TI - Vision loss and vascular compromise with facial and periocular injections. PMID- 26257236 TI - An atypical case of bilateral posterior scleritis in a patient with chronic lymphocytic leukemia. PMID- 26257237 TI - Primary hyperparathyroidism presenting as a brown cell tumour of the hallux. PMID- 26257238 TI - Minimally invasive non-surgical approach for the treatment of periodontal intrabony defects: a retrospective analysis. AB - AIM: The aim of this retrospective analysis was to assess healing of intrabony defects treated with minimally invasive non-surgical therapy (MINST). METHODS: A retrospective analysis was carried out in 35 consecutive intrabony defects treated by MINST (without any adjuncts) in 23 non-smoking patients. All defects had a radiographic intrabony component > 3 mm and had clinical and radiographic data available at baseline and 12 after treatment. Pre- and post-treatment radiographs were analysed and bone levels were compared by multilevel linear regression adjusted by latent variable method. RESULTS: Following MINST, the average PPD and CAL reduction in the intra-bony defects were 3.12 mm and 2.78 mm respectively (p < 0.001). The average radiographic intrabony vertical defect depth was reduced by 2.93 mm (from 6.74 mm to 3.81 mm) (p < 0.001), whereas the average defect angle changed from and 28.5 degrees at baseline to 44.4 degrees at re-evaluation (p < 0.001). Smaller initial defect angles and deeper initial defect depths were associated with greater defect depth reduction. Greater initial defect angles were associated with less defect angle change. CONCLUSIONS: This paper shows considerable clinical and radiographic improvements after MINST, therefore bringing evidence to support its efficacy for the treatment of intrabony defects in non-smokers. PMID- 26257239 TI - Sorafenib enriches epithelial cell adhesion molecule-positive tumor initiating cells and exacerbates a subtype of hepatocellular carcinoma through TSC2-AKT cascade. AB - Sorafenib is a specific adenosine triphosphate-competitive RAF inhibitor used as a first-line treatment of advanced hepatocellular carcinoma (HCC). However, the responses are variable, reflecting heterogeneity of the disease, while the resistance mechanism remains poorly understood. Here, we report that sorafenib treatment can exacerbate disease progression in both patient-derived xenografts and cell line-derived xenografts and that the therapeutic effect of the drug inversely covaries to the ratio of epithelial cell adhesion molecule-positive cells, which may be tumor initiating cells in HCC. The TSC2-AKT cascade mediates this sorafenib resistance. In response to sorafenib treatment, formation of the TSC1/2 complex is enhanced, causing increased phosphorylation of AKT, which contributes to up-regulation of "stemness"-related genes in epithelial cell adhesion molecule-positive cells and enhancement of tumorigenicity. The expression of TSC2 negatively correlated with prognosis in clinical sorafenib therapy. Furthermore, all-trans retinoic acid decreased AKT activity, reduced the epithelial cell adhesion molecule-positive cell population enriched by sorafenib, and potentiated the therapeutic effect of sorafenib in the patient-derived xenograft model. CONCLUSION: Our findings suggest that a subtype of HCC is not suitable for sorafenib therapy; this resistance to sorafenib can be predicted by the status of TSC2, and agents inducing differentiation of tumor initiating cells (e.g., all-trans retinoic acid) should improve the prognosis of this subtype of HCC. PMID- 26257240 TI - Insulin and insulin-like growth factor-1 can modulate the phosphoinositide-3 kinase/Akt/FoxO1 pathway in SZ95 sebocytes in vitro. AB - A recent hypothesis suggests that a high glycaemic load diet-associated increase of insulin-like growth factor-1 (IGF-1) and insulin may promote acne by reducing nuclear localization of the forkhead box-O1 (FoxO1) transcription factor via activation of the phosphoinositide-3-kinase (PI3K)/Akt pathway. Using SZ95 sebocytes as a model, we investigated the effect of the most important insulinotropic western dietary factors, IGF-1 and insulin on acne. SZ95 sebocytes were stimulated with different concentrations of IGF-1 and insulin (0.001, 0.01, 0.1 and 1 MUM) for 15 to 120 min +/- PI3K inhibitor LY294002 (50 MUM). Cytoplasmic and nuclear protein expression of p-Akt and p-FoxO1 as well as FoxO transcriptional activity was analysed. In addition, the proliferation and differentiation of sebocytes and their TLR2/4 expression were determined. We found that high concentrations of IGF-1 and insulin differentially stimulate the PI3K/Akt/FoxO1 pathway by an early up-regulation of cytoplasmic p-Akt and delayed up-regulation of p-FoxO1 resulting in FoxO1 shift to the cytoplasm and the reduction of FoxO transcriptional activity, physiological serum concentration had no effect. IGF-1 at concentrations of 0.1 and 1 MUM significantly reduced proliferation but increased differentiation of sebocytes to a greater extent than insulin (0.1 and 1 MUM), but up-regulated TLR2/4 expression to comparable extent. These data provide the first in vitro evidence that FoxO1 principally might be involved in the regulation of growth-factor-stimulatory effects on sebaceous lipogenesis and inflammation in the pathological condition of acne. However, the in vivo significance under physiological conditions remains to be elucidated. PMID- 26257241 TI - Adipocyte aminopeptidases in obesity and fasting. AB - This study checked the existence of a diverse array of aminopeptidase (AP) enzymes in high (HDM) and low (LDM) density microsomal and plasma membrane (MF) fractions from adipocytes of control, monosodium glutamate obese and food deprived rats. Gene expression was detected for ArgAP, AspAP, MetAP, and two AlaAP (APM and PSA). APM and PSA had the highest catalytic efficiency, whereas AspAP the highest affinity. Subcellular distribution of AP activities depended on metabolic status. Comparing catalytic levels, AspAP in HDM, LDM and MF was absent in obese and control under food deprivation; PSA in LDM was 3.5-times higher in obese than in normally fed control and control and obese under food deprivation; MetAP in MF was 4.5-times higher in obese than in food deprived obese. Data show new AP enzymes genetically expressed in subcellular compartments of adipocytes, three of them with altered catalytic levels that respond to whole-body energetic demands. PMID- 26257243 TI - Oxytocin Treatment, Circuitry, and Autism: A Critical Review of the Literature Placing Oxytocin Into the Autism Context. AB - Observed impairment in reciprocal social interaction is a diagnostic hallmark of autism spectrum disorders. There is no effective medical treatment for these problems. Psychological treatments remain costly, time intensive, and developmentally sensitive for efficacy. In this review, we explore the potential of oxytocin-based therapies for social impairments in autism. Evidence shows that acute oxytocin administration improves numerous markers critical to the social circuitry underlying social deficits in autism. Oxytocin may optimize these circuits and enhance reward, motivation, and learning to improve therapeutic outcomes. Despite this, the current evidence of therapeutic benefit from extended oxytocin treatment remains very limited. We highlight complexity in crossing from the laboratory to the autism clinical setting in evaluation of this therapeutic. We discuss a clinical trial approach that provides optimal opportunity for therapeutic response by using personalized methods that better target specific circuitry to define who will obtain benefit, at what stage of development, and the optimal delivery approach for circuitry manipulation. For the autism field, the therapeutic challenges will be resolved by a range of treatment strategies, including greater focus on specific interventions, such as oxytocin, that have a strong basis in the fundamental neurobiology of social behavior. More sophisticated and targeted clinical trials utilizing such approaches are now required, placing oxytocin into the autism context. PMID- 26257242 TI - A Method for Psychosocial Stress-Induced Reinstatement of Cocaine Seeking in Rats. AB - We describe a novel preclinical model of stress-induced relapse to cocaine use in rats using social defeat stress, an ethologically valid psychosocial stressor in rodents that closely resembles stressors that promote craving and relapse in humans. Rats self-administered cocaine for 20 days. On days 11, 14, 17, and 20, animals were subjected to social defeat stress or a nonstressful control condition following the session, with discrete environmental stimuli signaling the impending event. After extinction training, reinstatement was assessed following re-exposure to these discrete cues. Animals re-exposed to psychosocial stress-predictive cues exhibited increased serum corticosterone and significantly greater reinstatement of cocaine seeking than the control group, and active coping behaviors during social defeat episodes were associated with subsequent reinstatement magnitude. These studies are the first to describe an operant model of psychosocial stress-induced relapse in rodents and lay the foundation for future work investigating its neurobiological underpinnings. PMID- 26257244 TI - Gastric metastasis of pancreatic neuroendocrine tumor 5 years after surgical resection of the primary lesion. PMID- 26257245 TI - What is the role of sentinel lymph node biopsy in early-stage oral cavity carcinoma? PMID- 26257246 TI - One probe, two-channel imaging of nuclear and cytosolic compartments with orange and red emissive dyes. AB - Several new DNA-targeting probes that exhibit binding-induced 'turn on' fluorescence are presented. Two of the dyes, orange emissive 1, (E)-4-(4(-4 methylpiperazin-1-yl)phenyl)6-(4-(4-methylpi-perazin-1-yl)styryl)pyrimidin-2-ol), and red emissive 2, (E)-4-(4(-4-methyl-piperazin-1-yl)-phenyl)6-(4-(4 methylpiperazin-1-yl)styryl)-1,3-propanedionato-kappaO,kappaO']difluoroborane), are brightly fluorescent when bound to DNA, but are virtually non-fluorescent in aqueous solutions. Confocal fluorescence microscopy of live BT474, MCF7 and HEK293 cells demonstrates that both probes are cell permeable and rapidly accumulated intracellularly into cell nuclei and the cytosol. Taking advantage of their environmental sensitivity, these two pools of fluorophores are readily resolved into separate channels, and thus, a single dye allows two-color imaging of the nuclear and cytosolic compartments. PMID- 26257247 TI - Echocardiographic evaluation in subjects with alpha1-Antitrypsin deficiency. AB - BACKGROUND: alpha1-Antitrypsin (AAT) deficiency (AATD) is a genetic condition associated with early-onset panacinar emphysema and, less often, vascular disease. Recently, abnormal elastic properties of ascending aortic wall were described in ZZ genotype AATD subjects who incidentally showed an increased left ventricular mass. MATERIALS AND METHODS: To evaluate biventricular dimensions, valvular apparatus, systolic and diastolic function, 33 AATD subjects with ZZ genotype and 33 healthy subjects matched for age and sex underwent a complete echocardiographic assessment. RESULTS: Compared to controls, AATD subjects showed increased left ventricular mass (160 +/- 59 g vs. 121 +/- 70 g, P < 0.001), a higher incidence of left and right ventricular diastolic dysfunction (30% vs. 16%, P < 0.001 and 45% vs. 20%, P < 0.001, respectively) and mitral valve prolapse (35% vs. 6%, P < 0.001). In contrast, there was no difference between the two groups in diameters and systolic function of both ventricles and in the ejection fraction of left ventricle. The functions of aortic and tricuspidal valves were also similar. CONCLUSIONS: In the presence of greater left ventricular mass, a significantly higher incidence of left and right ventricular diastolic dysfunction and mitral valve prolapse occurs in AATD subjects (ZZ genotype). These findings strongly suggest an abnormal remodelling process in cardiac tissue in AATD. PMID- 26257248 TI - Medication errors detected in non-traditional databases: types of errors in methotrexate dosing as listed in four different Danish registers. AB - AIMS: We have looked for medication errors involving the use of low-dose methotrexate, by extracting information from Danish sources other than traditional pharmacovigilance databases. We used the data to establish the relative frequencies of different types of errors. METHODS: We searched four databases for cases involving low-dose methotrexate between 1999 and 2011: the Danish Patient Safety Databases (DPSD), controlled by the Danish National Agency for Patients' Rights and Complaints, the Patient Compensation Association (PCA), the Danish Poison and Information Centre (DPIC), and the online database of the Department for Patient Complaints (DPC). We categorized the place where the error occurred, the processes and types of error involved, the person responsible, and the clinical outcome. RESULTS: We identified 173 errors. In 109 (63%), either harm resulted or could not be excluded; of these, 26 (15%) resulted in serious harm, including nine deaths (5%); 53 (31%) involved incorrect daily administration; and 107 (62%) involved a dosing error. Sixteen events (9.2%) concerned insufficient or faulty monitoring, with four serious outcomes and two deaths. Prescription errors involving daily rather than weekly administration, by hospital physicians, were most likely to result in serious outcomes, including deaths. The error mechanism was evaluated in 129 events. Action-based errors comprised 50 % and knowledge-based errors 34 %. Action-based errors were more likely to result in completed errors, whereas knowledge-based errors more often resulted in near misses. CONCLUSIONS: The medication errors in this survey were most often action-based (50%) and knowledge-based (34%), suggesting that greater attention should be paid to education and surveillance of medical personnel who prescribe and monitor methotrexate, particularly physicians, who accounted for 40% of the errors. PMID- 26257249 TI - Effects of NAD(P)H quinone oxidoreductase 1 polymorphisms on stable warfarin doses in Korean patients with mechanical cardiac valves. AB - PURPOSE: NAD(P)H dehydrogenase, encoded by NAD(P)H quinone oxidoreductase 1 (NQO1), is an enzyme that catalyzes the reduction of quinones, including vitamin K. Given its potential role in vitamin K metabolism, this study aimed to investigate the effects of NQO1 polymorphisms on stable warfarin doses. METHODS: We tested a possible effect of gene polymorphisms on variability in warfarin response using 206 Korean patients with mechanical cardiac valves. Single nucleotide polymorphisms (SNPs) of NQO1 with a minor allele frequency of at least 15% were included. Also, genotypes of vitamin K epoxide reductase complex subunit 1 (VKORC1), cytochrome P450 (CYP) 2C9, CYP4F2, gamma-glutamyl carboxylase (GGCX), and GATA4 were determined. RESULTS: NQO1 rs1800566 (C>T) and rs10517 (C>T) were significantly associated with stable warfarin doses. Variant homozygote carriers required lower stable warfarin doses than those with wild-type C allele in rs1800566 (4.85 +/- 1.61 vs. 5.61 +/- 1.94 mg; p = 0.033), whereas patients with wild homozygote required lower doses than those with T allele in rs10517 (5.11 +/ 1.73 vs. 5.75 +/- 1.98 mg; p = 0.017). Similar results were obtained from stratified analysis using VKORC1 variant homozygote carriers in both SNPs. Multivariate analysis showed that rs10517 (C>T) increased contribution of gene variations to the overall warfarin dose variability from 42.5 to 43.8%. CONCLUSION: Our results demonstrate that NQO1 gene polymorphisms influence stable warfarin doses in Korean patients. PMID- 26257251 TI - Suitability of dispersive liquid-liquid microextraction for the in situ silylation of chlorophenols in water samples before gas chromatography with mass spectrometry. AB - Trace analysis of chlorophenols in water was performed by simultaneous silylation and dispersive liquid-liquid microextraction followed by gas chromatography with mass spectrometry. Dispersive liquid-liquid microextraction was carried out using an organic solvent lighter than water (n-hexane). The effect of different silylating reagents on the method efficiency was investigated. The influence of derivatization reagent volume, presence of catalyst and derivatization/extraction time on the yield of the derivatization reaction was studied. Different parameters affecting extraction efficiency such as kind and volume of extraction and disperser solvents, pH of the sample and addition of salt were also investigated and optimized. Under the optimum conditions, the calibration graphs were linear in the range of 0.05-100 ng/mL and the limit of detection was 0.01 ng/mL. The enrichment factors were 242, 351, and 363 for 4-chlorophenol, 2,4 dichlorophenol, and 2,4,6-trichlorophenol, respectively. The values of intra- and inter-day relative standard deviations were in the range of 3.0-6.4 and 6.1-9.9%, respectively. The applicability of the method was investigated by analyzing water and wastewater samples. PMID- 26257250 TI - Model-based meta-analysis of the effects of non-selective and alpha1-selective GABAA receptor agonists in healthy volunteers. AB - PURPOSE: To quantify pharmacokinetic (PK) and pharmacodynamic (PD) relationships of various classes of GABAA agonists in healthy volunteers, in order to investigate the sensitivity of the biomarker responses due to differing GABAA subtype selectivity and to explore the correlation between biomarker responses and side effects of these drugs. METHODS: A comprehensive search was conducted for published placebo-controlled clinical studies of non- and alpha1-selective GABAA drugs in healthy volunteers. PK/PD models were developed for concentrations and biomarker outcomes (saccadic eye movement (SEM), visual analogue scale (VAS), digit symbol substitution task (DSST), and critical flicker fusion test (CFFT)) extracted from included studies. Predicted responses and equivalent doses for biomarkers (based on predicted response) were used to compare drug effects. And the relationship between biomarkers and safety was explored by linear regression. RESULTS: A total of 2237 data from 163 articles were included. Based on PK and placebo effect modeling, linear biomarker-concentration relationships well fit the data. The alpha1-selective compounds had similar equivalent doses for VAS, DSST, and CFFT (4.7-6.7 mg), which were about three to seven times lower than that for SEM (14.4-35.5 mg), while such difference was less evident for non selective drugs. DSST had the highest correlations with incidences of somnolence and dizziness. CONCLUSIONS: The integral PK/PD models of GABAA agonists were established in healthy volunteers. SEM was identified as the most sensitive biomarker in differentiating GABAA receptor alpha1 subtype selective compounds. The exploratory analysis implied that different relationships existed between the drug effects on biomarkers and the adverse event profiles in healthy volunteers. PMID- 26257253 TI - Hepatoma in hepatitis B: Infectious disease or liver disease? PMID- 26257252 TI - Perspectives on next steps in classification of oro-facial pain - part 2: role of psychosocial factors. AB - This study was initiated by a symposium, in which the present authors contributed, organised by the International RDC/TMD Consortium Network in March 2013. The purpose of the study was to review the status of biobehavioural research - both quantitative and qualitative - related to oro-facial pain (OFP) with respect to the aetiology, pathophysiology, diagnosis and management of OFP conditions, and how this information can optimally be used for developing a structured OFP classification system for research. In particular, we address representation of psychosocial entities in classification systems, use of qualitative research to identify and understand the full scope of psychosocial entities and their interaction, and the usage of classification system for guiding treatment. We then provide recommendations for addressing these problems, including how ontological principles can inform this process. PMID- 26257254 TI - Association of adult attention deficit hyperactivity disorder subtypes and response to methylphenidate HCL treatment: A magnetic resonance spectroscopy study. AB - The effects of methylphenidate (MPH) treatment on N-acetyl aspartate (NAA), choline and creatine are being examined in individuals with different subtypes of attention deficit hyperactivity disorder (ADHD). Sixty ADHD subjects were included into the study aging between 18 and 60 years. Levels of NAA, creatine and choline in anterior cingulate cortex, cerebellum, striatum and dorsolateral prefrontal cortex were measured with magnetic resonance spectroscopy. Then, 10mg oral MPH was given to the subjects and the same metabolite levels were measured after an interval of 30min. Distribution of the patients according to the ADHD subtypes was as follows: 21 of them (35.0%) were in the inattentive type, 11 of them (18.3%) were in the hyperactive type and 28 of them were (46.7%) in the combined type. Changes of brain metabolite levels after MPH were found not to be statistically significantly different between the subtypes. The increase of choline levels after MPH compared to the levels of choline before MPH in striatum in the combined type patients were statistically significant. No clear association was found between ADHD subtypes and changes of brain metabolites with use of MPH in adult ADHD. PMID- 26257256 TI - Corrigendum: Rhodium-Catalyzed Asymmetric Synthesis of Silicon-Stereogenic Dibenzosiloles by Enantioselective [2+2+2] Cycloaddition. PMID- 26257257 TI - Corrigendum: Total Synthesis of Coralloidolides A, B, C, and E. PMID- 26257260 TI - Age related skeletal muscle atrophy and upregulation of autophagy in dogs. AB - Sarcopenia, the age related loss of muscle mass and strength, is a multifactorial condition that occurs in a variety of species and represents a major healthcare concern for older adults in human medicine. In veterinary medicine, skeletal muscle atrophy is often observed in dogs as they reach old age, but the process is not well understood. Autophagy is a mechanism for degradation and recycling of cellular constituents and is potentially involved in sarcopenia. The aim of the present study was to evaluate the expression of three markers of autophagy, Beclin 1, LC3 and p62, in muscle wasting of geriatric dogs, to establish whether the levels of autophagy change with increasing age. Muscle biopsies from 25 geriatric dogs were examined and compared with those from five healthy young dogs. Samples from older dogs, assessed by routine histology, histoenzymatic staining and immunohistochemistry, showed evidence of muscle atrophy, sarcoplasmic vacuolisation and mitochondrial alterations. Furthermore, in 80% of the muscle samples from the older dogs, marked intracytoplasmic staining for Beclin 1 and LC3 was observed. Significantly greater expression of LC3 II and Beclin 1, but lower expression of p62, was found by Western blotting, comparing muscle samples from old vs. young dogs. The results of the study suggest that enhanced autophagy might be one of the factors underlying muscle atrophy in dogs as they age. PMID- 26257261 TI - Symptomatic gossypiboma diagnosed by characteristic findings on endoscopic ultrasound. PMID- 26257262 TI - Novel mouse model for simulating microsurgical tumor excision with facial nerve preservation. AB - OBJECTIVES/HYPOTHESIS: To determine the feasibility of using a mouse tumor model as a microsurgical training tool for otolaryngology-head and neck surgery (OHNS) trainees. STUDY DESIGN: Animal study. METHODS: We injected athymic nude mice with human cutaneous squamous cell carcinoma (A431 cell line) deep to the parotid region overlying the masseter muscle. We sacrificed the animals 1 to 3 weeks postinjection, once a visible tumor growth was confirmed. We then asked 10 OHNS trainees to excise the tumor with preservation of the facial nerves under a high magnification dissecting microscope. The trainees graded the tasks in several areas of specific measures using a visual analogue scale (VAS) including 1) tumor texture, 2) surgical realism, 3) usefulness, and 4) difficulty of the task. RESULTS: Noticeable tumor growth occurred within 5 days following A431 cell injection and reached measureable size (0.5-1.5 cm) within 1 to 3 weeks. The tumor displaced the facial nerve laterally and medially, with few demonstrating infiltration of the nerve. VAS scores (+/- standard deviation) were 8.1 (+/- 1.7), 7.7 (+/- 2.5), 9.0 (+/- 0.9) and 6.6 (+/- 1.9) for tumor texture, surgical realism, usefulness, and the difficulty of the task, respectively. CONCLUSIONS: We demonstrate a novel, reliable and cost-effective mouse model for simulating tumor extirpation microsurgery with preservation of important neural structures. OHNS trainees have found this simulation model to be realistic, useful, and appropriately challenging. PMID- 26257263 TI - Influence of nitrogen sources on growth and fermentation performance of different wine yeast species during alcoholic fermentation. AB - In this study, the influence of twenty different single (i.e. 19 amino acids and ammonium sulphate) and two multiple nitrogen sources (N-sources) on growth and fermentation (i.e. glucose consumption and ethanol production) performance of Saccharomyces cerevisiae and of four wine-related non-Saccharomyces yeast species (Lachancea thermotolerans, Metschnikowia pulcherrima, Hanseniaspora uvarum and Torulaspora delbrueckii) was investigated during alcoholic fermentation. Briefly, the N-sources with beneficial effects on all performance parameters (or for the majority of them) for each yeast species were alanine, arginine, asparagine, aspartic acid, glutamine, isoleucine, ammonium sulphate, serine, valine and mixtures of 19 amino acids and of 19 amino acids plus ammonium sulphate (for S. cerevisiae), serine (for L. thermotolerans), alanine (for H. uvarum), alanine and asparagine (for M. pulcherrima), arginine, asparagine, glutamine, isoleucine and mixture of 19 amino acids (for T. delbrueckii). Furthermore, our results showed a clear positive effect of complex mixtures of N-sources on S. cerevisiae and on T. delbrueckii (although to a lesser extent) as to all performance parameters studied, whereas for L. thermotolerans, H. uvarum and M. pulcherrima, single amino acids affected growth and fermentation performance to the same extent as the mixtures. Moreover, we found groups of N-sources with similar effects on the growth and/or fermentation performance of two or more yeast species. Finally, the influences of N-sources observed for T. delbrueckii and H. uvarum resembled those of S. cerevisiae the most and the least, respectively. Overall, this work contributes to an improved understanding of how different N-sources affect growth, glucose consumption and ethanol production of wine-related yeast species under oxygen-limited conditions, which, in turn, may be used to, e.g. optimize growth and fermentation performance of the given yeast upon N-source supplementation during wine fermentations. PMID- 26257264 TI - Effect of specific light supply rate on photosynthetic efficiency of Nannochloropsis salina in a continuous flat plate photobioreactor. AB - In this work, Nannochloropsis salina was cultivated in a continuous-flow flat plate photobioreactor, working at different residence times and irradiations to study the effect of the specific light supply rate on biomass productivity and photosynthetic efficiency. Changes in residence times lead to different steady state cell concentrations and specific growth rates. We observed that cultures at steady concentration were exposed to different values of light intensity per cell. This specific light supply rate was shown to affect the photosynthetic status of the cells, monitored by fluorescence measurements. High specific light supply rate can lead to saturation and photoinhibition phenomena if the biomass concentration is not optimized for the selected operating conditions. Energy balances were applied to quantify the biomass growth yield and maintenance requirements in N. salina cells. PMID- 26257265 TI - Jorgensen-Hayashi catalysts supported on poly(ethylene glycol)s as highly efficient and reusable organocatalysts for the enamine-catalyzed asymmetric Michael reaction. AB - A new kind of recyclable and reusable PEG-supported Jorgensen-Hayashi catalyst is synthesized for the first time and proven to be efficient for the enamine catalyzed asymmetric Michael reaction with generally moderate to good diastereoselectivity and high to excellent enantioselectivity (up to 6 : 1 dr, 99% ee). The prepared PEG-supported catalyst can be recovered eight times and was found to provide similar diastereoselectivity and enantioselectivity to unsupported functional catalysts. PMID- 26257266 TI - Minimal synthetic cells to study integrin-mediated adhesion. AB - To shed light on cell-adhesion-related molecular pathways, synthetic cells offer the unique advantage of a well-controlled model system with reduced molecular complexity. Herein, we show that liposomes with the reconstituted platelet integrin alphaIIb beta3 as the adhesion-mediating transmembrane protein are a functional minimal cell model for studying cellular adhesion mechanisms in a defined environment. The interaction of these synthetic cells with various extracellular matrix proteins was analyzed using a quartz crystal microbalance with dissipation monitoring. The data indicated that integrin was functionally incorporated into the lipid vesicles, thus enabling integrin-specific adhesion of the engineered liposomes to fibrinogen- and fibronectin-functionalized surfaces. Then, we were able to initiate the detachment of integrin liposomes from these surfaces in the presence of the peptide GRGDSP, a process that is even faster with our newly synthesized peptide mimetic SN529, which specifically inhibits the integrin alphaIIb beta3 . PMID- 26257267 TI - Adjusting Hip Fracture Probability in Men and Women Using Hip Axis Length: the Manitoba Bone Density Database. AB - Most studies report that longer hip axis length (HAL) is associated with increased hip fracture risk in women, but comparable data in men are sparse. Using a registry of all dual-energy X-ray absorptiometry (DXA) results for Manitoba, Canada, we identified 4738 men and 50,420 women aged 40 yr and older with baseline hip DXA results, HAL measurements, and Fracture Risk Assessment Tool (FRAX) hip fracture probability computed with femoral neck bone mineral density (BMD). Population-based health service records were assessed for a subsequent hospitalization with a primary diagnosis of hip fracture. During mean 6.2 yr of follow-up, 70 men and 1020 women developed incident hip fractures. Mean HAL was significantly greater in those with vs without incident hip fractures (men 123.0 +/- 7.6 vs 121.3 +/- 7.4 mm, p = 0.050; women 106.9 +/- 6.2 vs 104.6 +/- 6.2 mm, p < 0.001). When adjusted for age and femoral neck BMD, each millimeter increase in HAL increased hip fracture risk by 3.6% in men (p = 0.022) and 4.6% in women (p < 0.001); this association was unaffected by sex (p value for interaction = 0.477). When adjusted for log-transformed FRAX hip fracture probability, each millimeter increase in HAL increased hip fracture risk by 3.4% in men (p = 0.031) and 4.8% in women (p < 0.001); this association was again unaffected by sex (p interaction = 0.409). A bilinear adjustment applicable to both men and women was developed: relative increase in hip fracture probability 4.7% for every millimeter that HAL is above the sex-specific average, relative decrease in hip fracture probability 3.8% for every millimeter that HAL is below the sex-specific average. We concluded that greater DXA-derived HAL is associated with increased incident hip fracture risk in both men and women, and this risk is independent of BMD and FRAX probability. PMID- 26257268 TI - An efficient, maintenance free and approved method for spectroscopic control and monitoring of blend uniformity: The moving F-test. AB - Dry powder mixing is a wide spread Unit Operation in the Pharmaceutical industry. With the advent of in-line Near Infrared (NIR) Spectroscopy and Quality by Design principles, application of Process Analytical Technology to monitor Blend Uniformity (BU) is taking a more prominent role. Yet routine use of NIR for monitoring, let alone control of blending processes is not common in the industry, despite the improved process understanding and (cost) efficiency that it may offer. Method maintenance, robustness and translation to regulatory requirements have been important barriers to implement the method. This paper presents a qualitative NIR-BU method offering a convenient and compliant approach to apply BU control for routine operation and process understanding, without extensive calibration and method maintenance requirements. The method employs a moving F-test to detect the steady state of measured spectral variances and the endpoint of mixing. The fundamentals and performance characteristics of the method are first presented, followed by a description of the link to regulatory BU criteria, the method sensitivity and practical considerations. Applications in upscaling, tech transfer and commercial production are described, along with evaluation of the method performance by comparison with results from quantitative calibration models. A full application, in which end-point detection via the F test controls the blending process of a low dose product, was successfully filed in Europe and Australia, implemented in commercial production and routinely used for about five years and more than 100 batches. PMID- 26257269 TI - In response to the usefulness of the stay suture technique in tracheostomy. PMID- 26257270 TI - Comparative proteomic profiling and possible toxicological mechanism of acute injury induced by carbon ion radiation in pubertal mice testes. AB - We investigated potential mechanisms of acute injury in pubertal mice testes after exposure to carbon ion radiation (CIR). Serum testosterone was measured following whole-body irradiation with a 2Gy carbon ion beam. Comparative proteomic profiling and Western blotting were applied to identify potential biomarkers and measure protein expression, and terminal dUTP nick end-labeling (TUNEL) was performed to detect apoptotic cells. Immunohistochemistry and immunofluorescence were used to investigate protein localization. Serum testosterone was lowest at 24h after CIR, and 10 differentially expressed proteins were identified at this time point that included eIF4E, an important regulator of initiation that combines with mTOR and 4EBP1 to control protein synthesis via the mTOR signaling pathway during proliferation and apoptosis. Protein expression and localization studies confirmed their association with acute injury following exposure to CIR. These three proteins may be useful molecular markers for detecting abnormal spermatogenesis following exposure to environmental and therapeutic radiation. PMID- 26257271 TI - Functional changes after early treatment of unilateral posterior cross-bite associated with mandibular shift: a systematic review. AB - The objective of this systematic review was to investigate whether oral functional asymmetry in children treated for unilateral functional posterior cross-bite disappears after orthodontic treatment with a resulting normalisation of oral functions. A literature search was carried out using PubMed, Web of Science and the Cochrane Library to locate longitudinal studies reporting on clinical oral functional changes, recorded by methods including masseter muscle thickness, bite force, masticatory/chewing cycle or electromyographic masticatory muscle activity, following the treatment of unilateral functional posterior cross bite. All potential articles were initially screened according to their title and abstract, the full text of selected articles was evaluated, and the final study selection was made based on the pre-defined criteria. Data extraction was subsequently carried out. The initial literature search identified 736 articles, with 12 articles fulfilling pre-defined criteria. Although there was a lack of high-quality prospective studies, based on the available evidence, results suggest that the abnormal masticatory cycle associated with functional posterior unilateral cross-bite tends to normalise following early cross-bite treatment. Masticatory muscle activity shows an increase after early functional unilateral posterior cross-bite treatment, and this activity approaches normal levels. Insufficient evidence was available to conclude on maximal molar bite force or masticatory muscle thickness changes following early treatment of functional unilateral posterior cross-bite. Results should be interpreted with caution due to the lack of high-quality controlled studies. Well-designed prospective studies with large patient samples and long-term follow-up are necessary before making reliable conclusions concerning change in functional asymmetry following unilateral functional posterior cross-bite correction. PMID- 26257272 TI - Colorectal cancer screening by colonoscopy: putting it into perspective. AB - Implementation of nationwide screening programs aims to decrease the disease burden of colorectal cancer (CRC) in the general population. Globally, most population screening programs for CRC are carried out by either fecal occult blood test, flexible sigmoidoscopy or colonoscopy. For screening programs with colonoscopy as the primary method, only circumstantial evidence from observational studies is available to prove its effectiveness, suggesting that colonoscopy effectively reduces CRC incidence and mortality. Currently, large randomized trials are being conducted to corroborate these findings. Besides the direct effect of a screening program for CRC, its protective effect is further enhanced by enrolment of patients that underwent polypectomy in surveillance programs. However, despite CRC screening and surveillance colonoscopies, interval CRC still occur. Those are predominantly located in the right-sided colon and potential explanations, besides unfavorable tumor characteristics, are preventable operator-dependent factors relating to the quality of the colonoscopy procedure. In an effort to reduce differences in endoscopists' performance and thereby the occurrence of interval CRC, quality indicators of colonoscopy have been introduced. In addition, emerging advanced colonoscopy techniques might contribute to improvement in polyp detection and removal. Meticulous inspection of the colonic mucosa not only results in the detection of advanced and relevant lesions, but also in the removal of many diminutive and small lesions leading to an increasing number of surveillance colonoscopies, known as the 'high-detection paradox'. More data on the cost-effectiveness of high-quality colonoscopy as a primary screening method and surveillance programs with intervals based on optimal risk stratification are eagerly awaited. PMID- 26257273 TI - Analysis of limb segments length and body proportion of southern Chinese children and adolescents. AB - AIM: This cross-sectional study was designed to characterize by age the ratios of limb segments length to height and extremities-trunk ratio and body proportions of southern Chinese children. METHODS: Data were collected from students (n = 4715) from five school, aged 6-17 years, in the city of Chongqing. Their standing height, sitting height, arm span, forearm length, upper arm length, leg length, lower leg length, and ratios of extremities to trunk length were determined. RESULTS: Sitting height, forearm length, upper arm length, arm span, and lower leg length were highly correlated with standing height (r > 0.9; P < 0.05). The ratio of extremities to trunk increased till about 13 years of age for both genders. CONCLUSIONS: The length of extremities and their ratio to sitting height reflect regular changes of growth in Chinese children as their age, and limb segments length is highly correlated with height. PMID- 26257274 TI - The role of the non-covalent beta-ionone-ring binding site in rhodopsin: historical and physiological perspective. AB - Bleached rhodopsin regenerates by way of the Schiff base formation between the 11 cis retinal and opsin. Recovery of human vision from light adapted states follows biphasic kinetics and each adaptive phase is assigned to two distinct classes of visual pigments in cones and rods, respectively, suggesting that the speed of Schiff base formation differs between iodopsin and rhodopsin. Matsumoto and Yoshizawa predicted the existence of a beta-ionone ring-binding site in rhodopsin, which has been proven by structural studies. They postulated that rhodopsin regeneration starts with a non-covalent binding of the beta-ionone ring moiety of 11-cis-retinal, followed by the Schiff base formation. Recent physiological investigation revealed that non-covalent occupation of the beta ionone ring binding site transiently activates the visual transduction cascade in the dark. In order to understand the role of non-covalent binding of 11-cis retinal to opsin during regeneration, we studied the kinetics of rhodopsin regeneration from opsin and 11-cis-retinal and found that the Schiff base formation is accelerated ~10(7) times compared to that between retinal and free amine. According to Cordes and Jencks, Schiff base formation in solution exhibits a bell-shaped pH dependence. However, we discovered that the rhodopsin formation is independent of pH over a wide pH range, suggesting that aqueous solvents do not have access to the Schiff base milieu during its formation. According to Hecht et al. the regeneration of iodopsin must be significantly faster than that of rhodopsin. Does this suggest that the Schiff base formation in iodopsin is favored due to its structural architecture? The iodopsin structure once solved would answer such a question as how molecular fine-tuning of retinal proteins realizes their dark adaptive functions. In contrast, bacteriorhodopsin does not require occupancy of a distinct beta-ionone ring-binding site, enabling an aldehyde without the cyclohexene ring to form a pigment. Studies of regeneration reaction of other retinal proteins, which are scarcely available, would clarify the molecular structure-phenotype relationships and their physiological roles. PMID- 26257275 TI - Tantalum rod implantation for femoral head osteonecrosis: survivorship analysis and determination of prognostic factors for total hip arthroplasty. AB - PURPOSE: The purpose of this study was to evaluate the moderate survival data of porous tantalum rod implants for the treatment of osteonecrosis of the femoral head (ONFH). Additionally, some independent prognostic factors for conversion to total hip arthroplasty (THA) were identified. METHODS: The porous tantalum rod population was obtained from a prospective, consecutive group of patients treated for Steinberg stage I and II osteonecrosis from April 2009 through July 2011. The historical core decompression and impaction of bone filling particle subjects underwent surgery from April 2007 through March 2009. Surgical data including time of surgery, blood loss, and cell transfusions were recorded. Post-operative values were measured for hospitalization length as well as days requiring a patient-controlled analgesia (PCA) pump. Primary outcomes were Harris hip score and survivorship analysis. Demographics and baseline characteristics included age, sex, etiology, bilateral disease, associated chronic systemic disease, Steinberg stage, Harris hip score, accompanied with bone marrow edema of femoral head, and osteonecrotic lesion size. RESULTS: Demographic/baseline characteristics were similar between two groups. At the post-operative follow-up of 62 months, Harris hip scores were significantly increased (P < 0.0001) when compared to that before surgery in both groups. The magnitude of increase in the tantalum rod implant group was significantly greater than that in the control group (P = 0.0426). With an average follow-up of 48 months (range, 38-62 months), the tantalum rod group had an 84.6 % survival rate. With an average follow-up of 72 months (range, 67-85 months), the control group had a 63.3 % survival rate. A comparison of Kaplan-Meier curves showed significantly higher cumulative survival rates (P = 0.048) for hips with implantation of the porous tantalum rod (74.1 % at 62 months) than for those with impaction composite bone material (49.9 % at 62 months). The Cox proportional-hazard model revealed that implantation of tantalum rod (P = 0.012), bone marrow edema (P = 0.003), corticosteroids intake (P = 0.007), and age less than 50 years (P = 0.014) were the independent prognostic factors related to conversion into THA. CONCLUSIONS: Compared with the traditional impaction composite bone material technique, implantation of tantalum rod in the treatment of Steinberg stages I and II ONFH can obtain better clinical results and higher cumulative survival rates. For patients without the use of corticosteroids, and especially for hips without bone marrow oedema, the clinical results from our study show highly encouraging survival rates and a delay in or prevention of conversion into THA. PMID- 26257276 TI - Geometrical analysis of stemless shoulder arthroplasty: a radiological study of seventy TESS total shoulder prostheses. AB - PURPOSE: The aim of this study was to investigate the ability of a stemless shoulder prosthesis to restore shoulder anatomy in relation to premorbid anatomy. METHODS: This prospective study was performed between May 2007 and December 2013. The inclusion criteria were patients with primary osteoarthritis (OA) who had undergone stemless total anatomic shoulder arthroplasty. Radiographic measurements were done on anteroposterior X-ray views of the glenohumeral joint. RESULTS: Sixty-nine patients (70 shoulders) were included in the study. The mean difference between premorbid centre of rotation (COR) and post-operative COR was 1 +/- 2 mm (range -3 to 5.8 mm). The mean difference between premorbid humeral head height (HH) and post-operative HH was -1 +/- 3 mm (range -9.7 to 8.5 mm). The mean difference between premorbid neck-shaft angle (NSA) and post-operative NSA was -3 +/- 12 degrees (range -26 to 20 degrees ). CONCLUSIONS: Stemless implants could be of help to reconstruct the shoulder anatomy. This study shows that there are some challenges to be addressed when attempting to ensure optimal implant positioning. The critical step is to determine the correct level of bone cut to avoid varus or valgus humeral head inclination and ensure correct head size. PMID- 26257277 TI - Clinical and radiological outcomes of unstable proximal humeral fractures treated with a locking plate and fibular strut allograft. AB - PURPOSE: To evaluate the clinical and radiological outcomes of unstable proximal humeral fractures (PHFs) treated with a locking plate and fibular strut allograft. METHODS: This study included 36 patients [7 men, 29 women; mean age, 68 years (range, 22-94 years)] with unstable PHFs with medial column disruption. All patients were treated with open reduction and internal fixation using a locking plate and fibular strut allograft. Post-operative assessment included clinical outcomes, shoulder range of motion, radiographic examination, and any complications. Post-operative radiological assessment including the humerus neck shaft angle (NSA) and the humeral head height was performed. RESULTS: At the mean two year follow-up visit, the mean American Shoulder and Elbow Society (ASES) and University of California, Los Angeles (UCLA) scores were 77 and 28, respectively. According to the UCLA rating scale, the result was excellent in six, good in 20, fair in six, and poor in four cases. According to the Paavolainen method, 31 patients had good results with an NSA of 130 +/- 10 degrees ; three patients showed fair results with an NSA of 100-120 degrees , and two patients experienced a poor result with an NSA of <100 degrees . When calculating the humeral head height, the mean loss of reduction was measured as 1.6 mm (from 10.8 or 9.2 mm). Varus collapse and avascular necrosis of the humeral head was noted in two patients for each condition. CONCLUSIONS: For unstable proximal humerus fractures, particularly in elderly patients with severe osteoporosis or in younger patients with a four-part fracture, locking plate fixation with a fibular strut allograft provided rigid medial support and showed satisfactory clinical and radiological outcomes. PMID- 26257278 TI - Transarticular plating for acute posterior sternoclavicular joint dislocations: a valid treatment option? AB - BACKGROUND: Restoration of the sternoclavicular joint after posterior dislocation is important for upper limb function. The proximity of neuro-vascular mediastinal structures makes open reduction and internal fixation (ORIF) a high-risk procedure. The ideal treatment strategy is still debated. Our aim is to review the treatment of acute posterior sternoclavicular joint dislocation with a locking compression plate. MATERIALS AND METHODS: We present our experience of transarticular plating using a locking compression plate for the treatment of three consecutive patients with posterior sternoclavicular dislocation (SCD). Our primary outcome measure was objective functional outcome using DASH (disability of the arm, shoulder and hand) and PROMIS (patient-reported outcomes measurement information system) questionnaires. All patients had a minimum follow-up of six months, and serial radiographs were reviewed to evaluate maintenance of reduction. RESULTS: All three patients presented a posterior SCD with instability refractory to closed reduction. In all three patients, we opted for surgical management using open reduction and fixation with a locking compression plate and allowed early mobilization at two weeks postoperatively. No complications were encountered during follow-up. Good functional outcomes were evidenced by DASH scores of 7.5, 20 and 30, and PROMIS scores were 53.8, 53.8 and 38.1 in each patient, respectively. CONCLUSION: Our experience of transarticular plating using a locking compression plate for posterior SCD is positive, as it allows early mobilization and resulted in good functional outcomes. PMID- 26257279 TI - Imatinib Treatment in PDGFRA-Negative Childhood Hypereosinophilic Syndrome. AB - We report a 4-year-old female who presented with severe hypereosinophilia (215.7 K/MUl) and end-organ dysfunction. Extensive evaluation including whole exome sequencing was performed, revealing no causative mutation. Initial treatment with corticosteroids, leukapheresis, and hydroxyurea decreased her absolute eosinophil count (AEC), although it remained elevated. Despite the absence of a PDGFRA mutation, an imatinib trial resulted in normalization of her AEC. Imatinib was discontinued after sustained normal counts for 1 month. AECs have remained normal for more than 1 year off therapy. This provides support for consideration of imatinib in the treatment of hypereosinophilia even in the absence of a known tyrosine kinase mutation. PMID- 26257280 TI - Relationship Between Peer Victimization and Posttraumatic Stress Among Primary School Children. AB - Peer victimization is a common stressor experienced by children. Although peer victimization has been studied extensively, few studies have examined the potential link between peer victimization and posttraumatic stress disorder (PTSD), and no studies of which we are aware have examined this link among children in primary school. The paucity of studies examining the link between PTSD and peer victimization in primary school is surprising because peer victimization occurs more frequently and is more likely to be physical among 7- and 8-year-old children. This study assessed the relationship between peer victimization and PTSD in a sample of 358 elementary school children (ages 6-11 years). Results indicated that peer victimization accounted for 14.1% of PTSD symptom severity among boys and 10.1% among girls. Additionally, we found gender differences in the types of peer victimization that were most associated with PTSD symptom severity (d = 0.38). The long-term developmental consequences that may be associated with peer victimization-linked PTSD symptomatology are discussed. PMID- 26257281 TI - THZ1 Reveals Roles for Cdk7 in Co-transcriptional Capping and Pausing. AB - The Cdk7 subunit of TFIIH phosphorylates RNA polymerase II (Pol II) during initiation, and, while recent studies show that inhibition of human Cdk7 negatively influences transcription, the mechanisms involved are unclear. Using in vitro transcription with nuclear extract, we demonstrate that THZ1, a covalent Cdk7 inhibitor, causes defects in Pol II phosphorylation, co-transcriptional capping, promoter proximal pausing, and productive elongation. THZ1 does not affect initiation but blocks essentially all Pol II large subunit C-terminal domain (CTD) phosphorylation. We found that guanylylation of nascent RNAs is length dependent and modulated by a THZ1-sensitive factor present in nuclear extract. THZ1 impacts pausing through a capping-independent block of DSIF and NELF loading. The P-TEFb-dependent transition into productive elongation was also inhibited by THZ1, likely due to loss of DSIF. Capping and pausing were also reduced in THZ1-treated cells. Our results provide mechanistic insights into THZ1 action and how Cdk7 broadly influences transcription and capping. PMID- 26257282 TI - Interaction between TBP and Condensin Drives the Organization and Faithful Segregation of Mitotic Chromosomes. AB - Genome/chromosome organization is highly ordered and controls various nuclear events, although the molecular mechanisms underlying the functional organization remain largely unknown. Here, we show that the TATA box-binding protein (TBP) interacts with the Cnd2 kleisin subunit of condensin to mediate interphase and mitotic chromosomal organization in fission yeast. TBP recruits condensin onto RNA polymerase III-transcribed (Pol III) genes and highly transcribed Pol II genes; condensin in turn associates these genes with centromeres. Inhibition of the Cnd2-TBP interaction disrupts condensin localization across the genome and the proper assembly of mitotic chromosomes, leading to severe defects in chromosome segregation and eventually causing cellular lethality. We propose that the Cnd2-TBP interaction coordinates transcription with chromosomal architecture by linking dispersed gene loci with centromeres. This chromosome arrangement can contribute to the efficient transmission of physical force at the kinetochore to chromosomal arms, thereby supporting the fidelity of chromosome segregation. PMID- 26257283 TI - Variable Glutamine-Rich Repeats Modulate Transcription Factor Activity. AB - Excessive expansions of glutamine (Q)-rich repeats in various human proteins are known to result in severe neurodegenerative disorders such as Huntington's disease and several ataxias. However, the physiological role of these repeats and the consequences of more moderate repeat variation remain unknown. Here, we demonstrate that Q-rich domains are highly enriched in eukaryotic transcription factors where they act as functional modulators. Incremental changes in the number of repeats in the yeast transcriptional regulator Ssn6 (Cyc8) result in systematic, repeat-length-dependent variation in expression of target genes that result in direct phenotypic changes. The function of Ssn6 increases with its repeat number until a certain threshold where further expansion leads to aggregation. Quantitative proteomic analysis reveals that the Ssn6 repeats affect its solubility and interactions with Tup1 and other regulators. Thus, Q-rich repeats are dynamic functional domains that modulate a regulator's innate function, with the inherent risk of pathogenic repeat expansions. PMID- 26257284 TI - Crosslink Mapping at Amino Acid-Base Resolution Reveals the Path of Scrunched DNA in Initial Transcribing Complexes. AB - RNA polymerase binds tightly to DNA to recognize promoters with high specificity but then releases these contacts during the initial stage of transcription. We report a site-specific crosslinking approach to map the DNA path in bacterial transcription intermediates at amino acid and nucleotide resolution. After validating the approach by showing that the DNA path in open complexes (RPO) is the same as in high-resolution X-ray structures, we define the path following substrate addition in "scrunched" complexes (RPITC). The DNA bulges that form within the transcription bubble in RPITC are positioned differently on the two strands. Our data suggest that the non-template strand bulge is extruded into solvent in complexes containing a 5-mer RNA, whereas the template strand bulge remains within the template strand tunnel, exerting stress on interactions between the beta flap, beta' clamp, and sigma3.2. We propose that this stress contributes to sigma3.2 displacement from the RNA exit channel, facilitating promoter escape. PMID- 26257285 TI - SpDamID: Marking DNA Bound by Protein Complexes Identifies Notch-Dimer Responsive Enhancers. AB - We developed Split DamID (SpDamID), a protein complementation version of DamID, to mark genomic DNA bound in vivo by interacting or juxtapositioned transcription factors. Inactive halves of DAM (DNA adenine methyltransferase) were fused to protein pairs to be queried. Either direct interaction between proteins or proximity enabled DAM reconstitution and methylation of adenine in GATC. Inducible SpDamID was used to analyze Notch-mediated transcriptional activation. We demonstrate that Notch complexes label RBP sites broadly across the genome and show that a subset of these complexes that recruit MAML and p300 undergo changes in chromatin accessibility in response to Notch signaling. SpDamID differentiates between monomeric and dimeric binding, thereby allowing for identification of half-site motifs used by Notch dimers. Motif enrichment of Notch enhancers coupled with SpDamID reveals co-targeting of regulatory sequences by Notch and Runx1. SpDamID represents a sensitive and powerful tool that enables dynamic analysis of combinatorial protein-DNA transactions at a genome-wide level. PMID- 26257287 TI - Dual antiplatelet therapy, drug-eluting stents and bioresorbable vascular scaffolds: Evolutionary perspectives. AB - Dual antiplatelet therapy reduces the risk of myocardial infarction, stent thrombosis, and cardiovascular mortality after percutaneous coronary intervention, but the optimal duration of therapy remains unclear. Stent thrombosis, one of the most feared complications of coronary intervention, is associated with high mortality and morbidity and is related in part to technical and patient-specific factors. Advances in device technology and better understanding of the pathophysiology of stent thrombosis have reduced the frequency of this devastating complication. Bioresorbable vascular scaffolds possess a number of advantageous features and are currently undergoing active investigation. Bioresorbable vascular scaffolds have been demonstrated to restore physiologic vasomotion, allow for late lumen enlargement, and upon full resorption remove the nidus for very late polymer reactions and resolve concerns of stent malapposition and side branch jailing. Based on the results from recent large-scale randomized trials, the optimal duration of dual antiplatelet therapy may depend on the choice of device type, as well as the individual patient risk of ischemic versus hemorrhagic complications. PMID- 26257286 TI - TAF11 Assembles the RISC Loading Complex to Enhance RNAi Efficiency. AB - Assembly of the RNA-induced silencing complex (RISC) requires formation of the RISC loading complex (RLC), which contains the Dicer-2 (Dcr-2)-R2D2 complex and recruits duplex siRNA to Ago2 in Drosophila melanogaster. However, the precise composition and action mechanism of Drosophila RLC remain unclear. Here we identified the missing factor of RLC as TATA-binding protein-associated factor 11 (TAF11) by genetic screen. Although it is an annotated nuclear transcription factor, we found that TAF11 also associated with Dcr-2/R2D2 and localized to cytoplasmic D2 bodies. Consistent with defective RLC assembly in taf11(-/-) ovary extract, we reconstituted the RLC in vitro using the recombinant Dcr-2-R2D2 complex, TAF11, and duplex siRNA. Furthermore, we showed that TAF11 tetramer facilitates Dcr-2-R2D2 tetramerization to enhance siRNA binding and RISC loading activities. Together, our genetic and biochemical studies define the molecular nature of the Drosophila RLC and elucidate a cytoplasmic function of TAF11 in organizing RLC assembly to enhance RNAi efficiency. PMID- 26257288 TI - Shape-Controlled Synthesis of Isotopic Yttrium-90-Labeled Rare Earth Fluoride Nanocrystals for Multimodal Imaging. AB - Isotopically labeled nanomaterials have recently attracted much attention in biomedical research, environmental health studies, and clinical medicine because radioactive probes allow the elucidation of in vitro and in vivo cellular transport mechanisms, as well as the unambiguous distribution and localization of nanomaterials in vivo. In addition, nanocrystal-based inorganic materials have a unique capability of customizing size, shape, and composition; with the potential to be designed as multimodal imaging probes. Size and shape of nanocrystals can directly influence interactions with biological systems, hence it is important to develop synthetic methods to design radiolabeled nanocrystals with precise control of size and shape. Here, we report size- and shape-controlled synthesis of rare earth fluoride nanocrystals doped with the beta-emitting radioisotope yttrium-90 ((90)Y). Size and shape of nanocrystals are tailored via tight control of reaction parameters and the type of rare earth hosts (e.g., Gd or Y) employed. Radiolabeled nanocrystals are synthesized in high radiochemical yield and purity as well as excellent radiolabel stability in the face of surface modification with different polymeric ligands. We demonstrate the Cerenkov radioluminescence imaging and magnetic resonance imaging capabilities of (90)Y-doped GdF3 nanoplates, which offer unique opportunities as a promising platform for multimodal imaging and targeted therapy. PMID- 26257289 TI - miRNA-mRNA crosstalk in esophageal cancer: From diagnosis to therapy. AB - The asymptomatic nature of esophageal cancer (EC) at early stages results in late clinical presentation leading to poor prognosis and limited success of therapeutic modalities. Efforts to identify diagnostic/prognostic markers have proven to be unsuccessful for translation into clinics. Hence, there is a pressing need for establishment of novel non-invasive biomarker for early diagnosis/better prognosis of EC. Recently, alteration in microRNA (miRNA) expression has emerged as an important hallmark of cancer. This review summarizes the differential expression of miRNAs in EC and addresses how their aberrant expression influences crucial biological processes such as apoptosis, cell proliferation, invasion and metastasis. Additionally, this review highlights the current status of circulating miRNA based diagnostic/prognostic markers. An effort has been made to find a connection between different miRNAs involved in EC and a detailed analysis has been done to screen out micoRNAs involved in prognosis and multidrug resistance. Further, investigation of these miRNAs would not only provide a gene therapy based strategy to prevent/treat cancer but also to reverse multidrug resistance leading to decreased requirement of harmful chemotherapeutic drugs. PMID- 26257290 TI - Next generation sequencing technologies for rare Mendelian disorders: striking potential and ongoing challenges. PMID- 26257292 TI - A new methodology for the determination of enzyme activity based on carbon nanotubes and glucose oxidase. AB - In this research, a novel enzyme activity analysis methodology is introduced as a new perspective for this area. The activity of elastase enzyme, which is a digestive enzyme mostly of found in the digestive system of vertebrates, was determined by an electrochemical device composed of carbon nanotubes and a second enzyme, glucose oxidase, which was used as a signal generator enzyme. In this novel methodology, a complex bioactive layer was constructed by using carbon nanotubes, glucose oxidase and a supporting protein, gelatin on a solid, conductive substrate. The activity of elastase was determined by monitoring the hydrolysis rate of elastase enzyme in the bioactive layer. As a result of this hydrolysis of elastase, glucose oxidase was dissociated from the bioactive layer, and following this the electrochemical signal due to glucose oxidase was decreased. The progressive elastase-catalyzed digestion of the bioactive layer containing glucose oxidase decreased the layer's enzymatic efficiency, resulting in a decrease of the glucose oxidation current as a function of the enzyme activity. The ratio of the decrease was correlated to elastase activity level. In this study, optimization experiments of bioactive components and characterization of the resulting new electrochemical device were carried out. A linear calibration range from 0.0303U/mL to 0.0729U/mL of elastase was reported. Real sample analyses were also carried out by the new electrochemical device. PMID- 26257293 TI - Comparison of the anti-inflammatory active constituents and hepatotoxic pyrrolizidine alkaloids in two Senecio plants and their preparations by LC-UV and LC-MS. AB - Two Senecio plants, Senecio cannabifolius Less. and its variety S. cannabifolius Less. var. integrifolius (Kiodz.) Kidam., were both used as the raw material of Feining granule, a traditional Chinese medicine product for treating respiratory diseases. In this study, the chemical profiles of these two plants were investigated and compared by liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR). A total number of 83 constituents, including 55 organic acids, 11 flavonoids, 4 alkaloids, 3 terpenes and 10 other types of compounds, were characterized. The results indicated that the levels of most flavonoids were higher in S. cannabifolius than in S. cannabifolius var. integrifolius, however, the levels of hepatotoxic pyrrolizidine alkaloids (PAs) were higher in S. cannabifolius var. integrifolius than in S. cannabifolius. Fifteen constituents were evaluated on lipopolysaccharides (LPS) induced RAW 264.7 cells, and eleven of them showed inhibition effect against nitric oxide (NO) production. Finally, the levels of ten major constituents (including seven anti-inflammatory active ones) and two PAs in Feining granule from two Senecio plants were determined and compared by the LC-UV and LC-MS methods, respectively. It was found that one organic acid (homogentisic acid) and two PAs (seneciphylline and senecionine) had higher contents in the preparation of S. cannabifolius var. integrifolius than in that of S. cannabifolius, however, the situations were inverse for the levels of four organic acids and flavonoids (chlorogenic acid, hyperoside, isoquercitrin, and isochlorogenic acid B). Based on the above results, S. cannabifolius might be a better raw material for Feining granule than S. cannabifolius var. integrifolius, because it contained more anti inflammatory constituents and less hepatotoxic PAs than the latter. However, more pharmacological evaluations should be carried out to support the selection. The results in this study were helpful for the quality control of Feining granule. PMID- 26257294 TI - An integrated approach to assess heavy metal source apportionment in peri-urban agricultural soils. AB - Three techniques (Isotope Ratio Analysis, GIS mapping, and Multivariate Statistical Analysis) were integrated to assess heavy metal pollution and source apportionment in peri-urban agricultural soils. The soils in the study area were moderately polluted with cadmium (Cd) and mercury (Hg), lightly polluted with lead (Pb), and chromium (Cr). GIS Mapping suggested Cd pollution originates from point sources, whereas Hg, Pb, Cr could be traced back to both point and non point sources. Principal component analysis (PCA) indicated aluminum (Al), manganese (Mn), nickel (Ni) were mainly inherited from natural sources, while Hg, Pb, and Cd were associated with two different kinds of anthropogenic sources. Cluster analysis (CA) further identified fertilizers, waste water, industrial solid wastes, road dust, and atmospheric deposition as potential sources. Based on isotope ratio analysis (IRA) organic fertilizers and road dusts accounted for 74-100% and 0-24% of the total Hg input, while road dusts and solid wastes contributed for 0-80% and 19-100% of the Pb input. This study provides a reliable approach for heavy metal source apportionment in this particular peri-urban area, with a clear potential for future application in other regions. PMID- 26257295 TI - Removal of heavy metals from aqueous phases using chemically modified waste Lyocell fiber. AB - In this study, an outstanding performance of chemically modified waste Lyocell for heavy metals treatment is reported. The sorbent, which was prepared by a simple and concise method, was able to bind heavy metals such as Pb(II), Cu(II) and Cd(II), with very high efficiencies. The binding mechanisms were studied through adsorption and standard characterization tests such as scanning electron microscopy, energy-dispersive spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction analyses. Adsorption kinetics was very fast and attained equilibrium within 5 min in all metals studied. The maximum single metal uptakes were 531.29+/-0.28 mg/g, 505.64+/-0.21 mg/g, and 123.08+/-0.26 mg/g for Pb(II), Cd(II) and Cu(II), respectively. In ternary metal systems, Cu(II) selectivity was observed and the underlying factors were discussed. The sorbent by its nature, could be very effective in treating large volumes of wastewater with the contact of very little amount. PMID- 26257297 TI - Mechanism and Kinetics of Li2S Precipitation in Lithium-Sulfur Batteries. AB - The kinetics of Li2 S electrodeposition onto carbon in lithium-sulfur batteries are characterized. Electrodeposition is found to be dominated by a 2D nucleation and growth process with rate constants that depend strongly on the electrolyte solvent. Nucleation is found to require a greater overpotential than growth, which results in a morphology that is dependent on the discharge rate. PMID- 26257296 TI - Identification of Discrete Prognostic Groups in Ewing Sarcoma. AB - BACKGROUND: Although multiple prognostic variables have been proposed for Ewing sarcoma (EWS), little work has been done to further categorize these variables into prognostic groups for risk classification. PROCEDURE: We derived initial prognostic groups from 2,124 patients with EWS in the SEER database. We constructed a multivariable recursive partitioning model of overall survival using the following covariates: age; stage; race/ethnicity; sex; axial primary; pelvic primary; and bone or soft tissue primary. Based on this model, we identified risk groups and estimated 5-year overall survival for each group using Kaplan-Meier methods. We then applied these groups to 1,680 patients enrolled on COG clinical trials. RESULTS: A multivariable model identified five prognostic groups with significantly different overall survival: (i) localized, age <18 years, non-pelvic primary; (ii) localized, age <18, pelvic primary or localized, age >=18, white, non-Hispanic; (iii) localized, age >=18, all races/ethnicities other than white, non-Hispanic; (iv) metastatic, age <18; and (v) metastatic, age >=18. These five groups were applied to the COG dataset and showed significantly different overall and event-free survival based upon this classification system (P < 0.0001). A sub-analysis of COG patients treated with ifosfamide and etoposide as a component of therapy evaluated these findings in patients receiving contemporary therapy. CONCLUSIONS: Recursive partitioning analysis yields discrete prognostic groups in EWS that provide valuable information for patients and clinicians in determining an individual patient's risk of death. These groups may enable future clinical trials to adjust EWS treatment according to individualized risk. PMID- 26257298 TI - [Axillary lymph node metastases with an occult breast: About 16 cases from a cohort of 7770 patients]. AB - OBJECTIVES: Isolated axillary lymph node metastases is an unusual clinical presentation of breast carcinoma. We studied its different issues. METHODS: This study is a follow-up study of 16patients, treated between 1996 and 2012, presenting with axillary metastases with an occult breast carcinoma, which could not be identified by physical examination nor by a conventional imaging or a breast MRI. Clinical characteristics, histological analysis, treatment, monitoring and five-year survival rate were studied. RESULTS: The incidence of this kind of breast cancer was 0.20%. A breast MRI was performed in 75% of the patients. The histology of these tumors showed a rate of hormono-sensibility of 50% and an HER2 overexpression of 44%. Sixty-nine percent of the patients had no breast surgery or radiotherapy; global five-year survival rate for these women was 77.4%+/-11.5. CONCLUSION: The survival rates of this study should lead the practitioner to choose a less aggressive breast therapy. Moreover, the histological characteristics explain the high metastatic potential of these tumors, and relate them to the HER2+ subclass of gene expression patterns of breast carcinomas. PMID- 26257299 TI - A Theory of Waiting Time Reporting and Quality Signaling. AB - We develop a theoretical model to study a policy that publicly reports hospital waiting times. We characterize two effects of such a policy: the 'competition effect' that drives hospitals to compete for patients by increasing service rates and reducing waiting times and the 'signaling effect' that allows patients to distinguish a high-quality hospital from a low-quality one. While for a low quality hospital both effects help reduce waiting time, for a high-quality hospital, they act in opposite directions. We show that the competition effect will outweigh the signaling effect for the high-quality hospital, and consequently, both hospitals' waiting times will be reduced by the introduction of the policy. This result holds in a policy environment where maximum waiting time targets are not binding. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26257300 TI - The gut microbiota in human energy homeostasis and obesity. AB - Numerous studies of rodents suggest that the gut microbiota populations are sensitive to genetic and environmental influences, and can produce or influence afferent signals that directly or indirectly impinge on energy homeostatic systems affecting both energy balance (weight gain or loss) and energy stores. Fecal transplants from obese and lean human, and from mouse donors to gnotobiotic mice, result in adoption of the donor somatotype by the formerly germ-free rodents. Thus, the microbiota is certainly implicated in the development of obesity, adiposity-related comorbidities, and the response to interventions designed to achieve sustained weight reduction in mice. More studies are needed to determine whether the microbiota plays a similarly potent role in human body weight regulation and obesity. PMID- 26257301 TI - ErbB-2 signaling plays a critical role in regulating androgen-sensitive and castration-resistant androgen receptor-positive prostate cancer cells. AB - While androgen deprivation therapy (ADT) reduces tumor burden, autocrine growth factor loops such as human epidermal growth factor receptor 2 (HER2/ErbB-2/neu) have been proposed to contribute to prostate cancer (PCa) survival and relapse. However, the role of ErbB-2 in regulating androgen-sensitive (AS) and castration resistant (CR) cell proliferation remains unclear. Here, we determined the role of ErbB-2 in PCa progression and survival under steroid-reduced conditions using two independent PCa cell progression models. In AR-positive androgen-independent (AI) PCa cells that exhibit the CR phenotype, ErbB-2 was constitutively activated, compared to corresponding AS PCa cells. In AS LNCaP C-33 cells, androgen-induced ErbB-2 activation through ERK1/2 mediates PCa cell proliferation. Further, the ErbB-2-specific but not EGFR-specific inhibitor suppresses basal and androgen-stimulated cell proliferation and also blocks ERK1/2 activation. ErbB-2 ectopic expression and cPAcP siRNA transfection of LNCaP C-33 cells each increases ErbB-2 tyrosine phosphorylation, correlating with increased AI PSA secretion and cell proliferation. Conversely, trapping ErbB-2 by transfected endoplasmic reticulum-targeting ScFv5R expression vector abolished DHT-induced LNCaP C-33 cell growth. Moreover, inhibition of ErbB-2 but not EGFR in AI LNCaP C-81 and MDA PCa2b-AI PCa cells significantly abolished AI cell growth. In contrast to androgens via ErbB-2/ERK1/2 signaling in AS PCa cells, the inhibition of ErbB-2 abrogated AI cell proliferation by inhibiting the cell survival protein Akt in those AI cells. These results suggest that ErbB-2 is a prominent player in mediating the ligand-dependent and -independent activation of AR in AS and AI/CR PCa cells respectively for PCa progression and survival. PMID- 26257302 TI - RACK1 and beta-arrestin2 attenuate dimerization of PDE4 cAMP phosphodiesterase PDE4D5. AB - PDE4 family cAMP-selective cyclic nucleotide phosphodiesterases are important in the regulation of cAMP abundance in numerous systems, and thereby play an important role in the regulation of PKA and EPAC activity and the phosphorylation of CREB. We have used the yeast 2-hybrid system to demonstrate recently that long PDE4 isoforms form homodimers, consistent with data obtained recently by structural studies. The long PDE4 isoform PDE4D5 interacts selectively with beta arrestin2, implicated in the regulation of G-protein-coupled receptors and other cell signaling components, and also with the beta-propeller protein RACK1. In the present study, we use 2-hybrid approaches to demonstrate that RACK1 and beta arrestin2 inhibit the dimerization of PDE4D5. We also show that serine-to-alanine mutations at PKA and ERK1/2 phosphorylation sites on PDE4D5 detectably ablate dimerization. Conversely, phospho-mimic serine-to-aspartate mutations at the MK2 and oxidative stress kinase sites ablate dimerization. Analysis of PDE4D5 that is locked into the dimeric configuration by the formation of a trans disulfide bond between Ser261 and Ser602 shows that RACK1 interacts strongly with both the monomeric and dimeric forms, but that beta-arrestin2 interacts exclusively with the monomeric form. This is consistent with the concept that beta-arrestin2 can preferentially recruit the monomeric, or "open," form of PDE4D5 to beta2 adrenergic receptors, where it can regulate cAMP signaling. PMID- 26257304 TI - Activity, abundance and structure of ammonia-oxidizing microorganisms in plateau soils. AB - Both ammonia-oxidizing archaea (AOA) and bacteria (AOB) can be involved in biotransformation of ammonia to nitrite in soil ecosystems. However, the distribution of AOA and AOB in plateau soils and influential factors remain largely unclear. In the present study, the activity, abundance and structure of ammonia oxidizers in different soils on the Yunnan Plateau were assessed using potential nitrification rates (PNRs), quantitative PCR assay and clone library analysis, respectively. Wide variation was found in both AOA and AOB communities in plateau soils. PNRs showed a significant positive correlation with AOB abundance. Both were determined by the ratio of organic carbon to nitrogen (C/N) and total phosphorous (TP). AOB could play a more important role in ammonia oxidation. AOB community diversity was likely affected by soil total nitrogen (TN) and total organic carbon (TOC) and was usually higher than AOA community diversity. Moreover, Nitrososphaera- and Nitrosospira-like organisms, respectively, were the dominant AOA and AOB in plateau soils. AOA community structure was likely shaped by TP and C/N, while AOB community structure was determined by pH. PMID- 26257303 TI - Extracellular superoxide provokes glutathione efflux from Escherichia coli cells. AB - The aim of the study was to elucidate a possible relationship between transmembrane cycling of glutathione and changes in levels of external superoxide. Exposure of growing Escherichia coli to exogenous reactive oxygen species (ROS) generated by xanthine and xanthine oxidase (XO) stimulates reversible glutathione (GSH) efflux from the cells that is considerably lowered under phosphate starvation. This GSH efflux is prevented by exogenous SOD, partially inhibited by catalase, and is not dependent on the GSH exporter CydDC. The gamma-glutamyl transpeptidase (GGT) deficiency completely prevents a return of GSH to the cytoplasm. In contrast to wild-type E. coli, mutants devoid of GGT and glutathione reductase (GOR) show enhanced accumulation of oxidized glutathione in the medium after exposure to xanthine and XO. Under these conditions, sodC, ggt and especially gshA mutants reveal more intensive and prolonged inhibition of growth than wild-type cells. Treatment with XO does not influence E. coli viability, but somewhat increases the number of cells with lost membrane potential. In summary, data obtained here indicate that transmembrane cycling of GSH may be involved in E. coli protection against extracellular ROS and may promote rapid growth recovery. PMID- 26257305 TI - Cellular Response to Linear and Branched Poly(acrylic acid). AB - Poly(acrylic acid-co-sodium acrylate) (PNaA) is a pH-responsive polymer with potential in anticancer drug delivery. The cytotoxicity and intracellular effects of 3-arm star, hyperbranched and linear PNaA were investigated with L1210 progenitor leukemia cells and L6 myoblast cells. Free solution capillary electrophoresis demonstrated interactions of PNaA with serum proteins. In a 72 h MTT assay most PNaAs exhibited a IC50 between 7 and 14 mmol L(-1), showing that precipitation may be a sufficient purification for PNaA dilute solutions. Dialyzed 3-arm star and hyperbranched PNaA caused an increase in L6 cell viability, challenging the suitability of MTT as cytotoxicity assay for PNaA. Fluorescent confocal microscopy revealed merging of cellular lipids after exposure to PNaA, likely caused by serum starvation. PMID- 26257306 TI - Peripheral cues and gaze direction jointly focus attention and inhibition of return. AB - Centrally presented gaze cues typically elicit a delayed inhibition of return (IOR) effect compared to peripheral exogenous cues. We investigated whether gaze cues elicit early onset IOR when presented peripherally. Faces were presented in the left or right peripheral hemifields, which then gazed upward or downward. A target appeared in one of four oblique spatial locations giving the cue and target horizontal or vertical congruency, both, or neither. After establishing that peripheral movement and gaze direction jointly facilitate target processing at short durations (200 ms: Experiment 1), IOR was evident for peripheral motion at longer time courses (800 and 2400 ms: Experiment 2). Only after 2400 ms did gaze direction additionally contribute to IOR for the specific gazed at location, showing the inverse pattern of response times to Experiment 1. The onset of IOR for gaze cues is independent from peripheral exogenous cueing but nevertheless contributes to the allocation of attention. PMID- 26257307 TI - Exposure of mental health nurses to violence associated with job stress, life satisfaction, staff resilience, and post-traumatic growth. AB - Workplace violence towards health workers in hospitals and in mental health units in particular is increasing. The aim of the present study was to explore the effects of exposure to violence, job stress, staff resilience, and post-traumatic growth (PTG) on the life satisfaction of mental health nurses. A descriptive, cross-sectional design was used. The sample consisted of mental health nurses (n = 118) working in a large mental health centre in Israel. Verbal violence by patients was reported by 88.1% of the nurses, and 58.4% experienced physical violence in the past year. Physical and verbal violence towards nurses was correlated with job stress, and life satisfaction was correlated with PTG and staff resilience. Linear regression analyses indicated that life satisfaction was mainly affected by PTG, staff resilience, and job stress, and less by exposure to verbal and physical violence. The present study is the first to show that, although mental health nurses are frequently exposed to violence, their life satisfaction is affected more by staff resilience, PTG, and job stress than by workplace violence. Therefore, it is recommended that intervention programmes that contribute to PTG and staff resilience, as well as those that reduce job stress among mental health nurses, be explored and implemented. PMID- 26257308 TI - The effect of spiritual interventions addressing existential themes using a narrative approach on quality of life of cancer patients: a systematic review and meta-analysis. AB - OBJECTIVE: The aim of this study was to examine the effect of spiritual interventions on quality of life of cancer patients. METHODS: We conducted our search on June 6, 2014 in Medline, PsycINFO, Embase, and PubMed. All clinical trials were included that compared standard care with a spiritual intervention that addressed existential themes using a narrative approach. Study quality was evaluated by the Cochrane Risk of Bias Tool. RESULTS: A total of 4972 studies were identified, of which 14 clinical trials (2050 patients) met the inclusion criteria, and 12 trials (1878 patients) were included in the meta-analysis. The overall risk of bias was high. When combined, all studies showed a moderate effect (d) 0.50 (95% CI = 0.20-0.79) 0-2 weeks after the intervention on overall quality of life in favor of the spiritual interventions. Meta-analysis at 3-6 months after the intervention showed a small insignificant effect (0.14, 95% CI = -0.08 to 0.35). Subgroup analysis including only the western studies showed a small effect of 0.17 (95% CI = 0.05-0.29). Including only studies that met the allocation concealment criteria showed an insignificant effect of 0.14 (95% CI = 0.05 to 0.33). CONCLUSIONS: Directly after the intervention, spiritual interventions had a moderate beneficial effect in terms of improving quality of life of cancer patients compared with that of a control group. No evidence was found that the interventions maintained this effect up to 3-6 months after the intervention. Further research is needed to understand how spiritual interventions could contribute to a long-term effect of increasing or maintaining quality of life. PMID- 26257309 TI - Heterogeneous MR arthrography findings in patients with subacromial impingement syndrome - Diagnostic subgroups? AB - BACKGROUND: Subacromial Impingement Syndrome (SIS) is frequently diagnosed, but treatment results vary greatly. It is increasingly reported that SIS symptoms are caused by various underlying mechanisms that need distinctive treatment strategies. We evaluated a set of specific MRI Arthrography (MRA) characteristics that have been related with underlying mechanisms for SIS in the literature, in patients with SIS. METHODS: In 47 patients diagnosed with SIS, MRA characteristics were evaluated and categorized into categories of potential underlying mechanisms: (1) extrinsic: e.g. acromion shape; (2) intrinsic: e.g. tendinosis; (3) dynamic: e.g. signs of glenohumeral (micro-)instability. Control values were obtained from the literature. With cluster analysis, potential patient subgroups were assessed. RESULTS: In 17 (36.2%) patients originally diagnosed with SIS, specific other conditions were found, including rotator cuff tears and labrum lesions. In the remaining 30, all had positive signs of at least one of the predefined underlying mechanisms. Patients could be categorized into 2 groups: predominantly findings corresponding with extrinsic/structural causes, or with dynamic/(micro)instability. CONCLUSIONS: MRA characteristics in patients with SIS symptoms are heterogeneous and many patients have specific other shoulder conditions causing symptoms. Patients without specific other conditions have MRA characteristics associated with either extrinsic (structural), or dynamic (e.g. micro-instability) underlying mechanisms. PMID- 26257310 TI - Describing Quality and Sensory Attributes of 3 Mango (Mangifera indica L.) Cultivars at 3 Ripeness Stages Based on Firmness. AB - To determine the ideal ripening stage for consumption of the mango cultivars, "Ataulfo," "Haden," and "Tommy Atkins"; fruits at 3 flesh firmness levels (ripeness stages) were evaluated by a trained panel using descriptive analysis after instrumental measurements were made. After harvest, all fruits were ripened to allow softening and quality and sensory attribute changes. Ripening changes during softening of Ataulfo mangos were expressed by a characteristic increase in the perception of "tropical fruit" and "peach" aromas, an increase in "juiciness," "sweetness," and "tropical fruit" flavor, while "fibrousness," "chewiness," and "sourness" decreased. Similar desirable sensory changes were also detected during softening of Haden mangos; an increase in tropical fruit and peach aromas, sweetness and tropical fruit flavor, and a decrease in chewiness, sourness, and bitterness. Softening of Tommy Atkins mangos was followed by reduced chewiness and sourness and increased peach aroma. Softening of all cultivars was followed by decreased sourness and titratable acidity (TA) and increased soluble solids concentration (SSC) and SSC:TA ratio. The results indicate that mango ripening leads to increased expression of sensory attributes such as tropical fruit and peach aromas, tropical flavor, and sweetness that have been related to improved eating quality and these final changes in sensory quality attributes are specific for each cultivar. For example, Ataulfo and Haden mangos had greater improvement in quality and sensory attributes related to fruit eating quality during ripening-softening than Tommy Atkins. In our consumer test, these quality-sensory attributes expressed during ripening that were perceived by the trained panel were also validated, supporting the need for a controlled ripening protocol in mangos. PMID- 26257311 TI - Late diagnosis: a factor associated with death from visceral leishmaniasis in elderly patients. AB - INTRODUCTION: Visceral leishmaniasis (VL) is among the seven global endemic diseases assigned a high priority by the World Health Organization. In Latin America, most cases occur in Brazil. Despite the availability of intensive treatment resources and protocols for specific treatment, lethality rates for VL have increased in several regions in the country over the past 10 years, particularly in patients under one and over 50 years of age. As the growth of the elderly population accelerates in Brazil, VL poses a greater challenge to public health. Given the scarcity of studies addressing the disease in this age group, the purpose of this study was to identify factors associated with VL lethality among the elderly. METHODS/KEY FINDINGS: This analytical, cross-sectional epidemiological study comprised 80 elderly patients who sought treatment at the teaching hospital of the Universidade Federal de Mato Grosso do Sul, Campo Grande, MS, Brazil, in the period 2000-2013.Clinical, laboratory and treatment variables were investigated from records of elderly patients with VL diagnosis confirmed by at least one laboratory test positive (culture for parasite or direct parasitological examination; reactive immunofluorescence; immunochromatographic test with recombinant antigens) or patients without laboratory confirmation who lived in endemic areas and responded favorably to therapeutic trial, as defined by the Brazilian Ministry of Health. Of the 80 patients included, 78 tested positive to at least one exam; in two cases, diagnosis was based on clinical and epidemiological criteria. The lethality rate was 20%. Multivariate analysis revealed an association between death and time elapsed from symptom onset. PMID- 26257312 TI - Australian case managers' views about the impact of antipsychotic medication on mental health consumers. AB - This study examined case managers' views about antipsychotic medications and the impact of side-effects on mental health consumers in a community setting. Nine case managers were purposively sampled and interviewed. Content analysis was used to generate a series of themes. The findings indicated that case managers perceived that a lack of consumer insight was one of the main reasons for wanting to reduce, or altogether cease, antipsychotic medication. However, case managers lacked an adequate level of knowledge about antipsychotic medication side effects. Without a sufficient level of knowledge, case managers may be unable to fully address consumers' concerns. PMID- 26257313 TI - The importance of emotional intelligence and meaning in life in psycho-oncology. AB - OBJECTIVE: Cancer was considered the disease of the 20th century, and the management, treatment, and adaptation of patients to general wellbeing were worldwide concerns. Emotional intelligence has frequently been associated with wellbeing and considered one important factor to optimal human functioning. The purpose of the present study was to test the differences regarding the relationship between emotional intelligence, purpose in life, and satisfaction with life between cancer and healthy people. METHODS: This model was tested using structural path analysis in two independent samples. First, in a general Portuguese population without chronic disease, 214 participants (nmale = 41, nfemale = 173; Mage = 53). Second, in 202 patients with cancer (nmale = 40, nfemale = 162; Mage = 58.65). A two-step methodology was used to test the research hypothesis. RESULTS: First, a confirmatory factor analysis supported the measurement model. All factors also show reliability, convergent, and discriminate validity. Second, the path coefficients for each model indicate that the proposed relationships differ significantly according to the groups. The perception capacities of emotional intelligence were more related to satisfaction with life and purpose in life in oncologic patients than in the general population without chronic disease, specifically emotional understanding and regulation. Likewise, the relationship between purpose in life and satisfaction with life in oncologic patients was significantly higher than for the general population. CONCLUSION: The current findings thus suggest that emotional intelligence and purpose in life are potential components to promoting satisfaction in life in healthy people and more so in oncologic patients. PMID- 26257314 TI - Low-Temperature Synthesis of Large-Scale Molybdenum Disulfide Thin Films Directly on a Plastic Substrate Using Plasma-Enhanced Chemical Vapor Deposition. AB - By plasma-enhanced chemical vapor deposition, a molybdenum disulfide (MoS2 ) thin film is synthesized directly on a wafer-scale plastic substrate at below 300 degrees C. The carrier mobility of the films is 3.74 cm(2) V(-1) s(-1) . Also, humidity is successfully detected with MoS2 -based sensors fabricated on the flexible substrate, which reveals its potential for flexible sensing devices. PMID- 26257315 TI - Infant gastro-oesophageal reflux disease (GORD): Australian GP attitudes and practices. AB - AIM: The aim of this study was to evaluate the attitudes and practices of Australian general practitioners (GPs) regarding infant gastro-oesophageal reflux disease (GORD) diagnosis and management. METHODS: A national cross-sectional survey, involving a random sample of currently practising Australian GPs (n = 2319) was undertaken between July and September 2011. GPs attitudes and management of infant GORD were surveyed via an online and paper-based 41-item questionnaire. RESULTS: In total, 400 responses were analysed (17.24% response rate). The majority of GPs employed empirical trials of acid-suppression medication and/or lifestyle modifications to diagnose infant GORD. GPs frequently recommended dietary modification despite the belief that they were only moderately effective at best. In addition, GPs frequently prescribed acid suppression medication, despite concerns regarding their safety in the infant population. Other GP concerns included the lack of clinical guidelines and education for GPs about infant GORD, as well as the level of evidence available for the safety and efficacy of diagnostic tests and treatments. CONCLUSION: Despite the important role Australian GPs play in the diagnosis and management of infant GORD, high-level evidence-based guidelines for GPs are lacking. Consequently, GPs engage in diagnostic and management practices despite their concerns regarding the safety and effectiveness. PMID- 26257316 TI - Expression of mRNA in the frontal cortex and hypothalamus in a rat model of acute carbon dioxide poisoning. AB - Acute carbon dioxide (CO2) poisoning causes no specific features that are revealed upon autopsy, and the pathophysiological mechanism of this syndrome is unclear. To address this issue, in the present study, we exposed rats to CO2 concentrations ranging from 10% to 60% and determined the effects on mRNA expression. According to the results of Gene Ontology (GO) and cluster analyses of microarrays data, we selected the following genes for further analysis: alkylglycerone phosphate synthase (Agps), hypocretin (Hcrt), tyrosine hydroxylase (Th), heat shock protein beta 2 (Hspb2), and opioid receptor delta 1 (Oprd1) expressed in the frontal cortex and renin (Ren), pancreatic polypeptide (Ppy), corticotropin releasing hormone receptor 2 (Crhr2), carbonic anhydrase 1 (Car1), and hypocretin receptor 1 (Hcrtr1) expressed in the hypothalamus. We found significant differences between the expression levels of Agps and Hspb2 mRNAs in the frontal cortex and that of Ppy, Crhr2 mRNAs in the hypothalamus in the presence of high concentrations of CO2. Further investigation of these genes may clarify the pathophysiology of acute CO2 poisoning and facilitate the development of novel forensic tests that can diagnose the cause of death. PMID- 26257317 TI - Identification and quantification of metabolites of AB-CHMINACA in a urine specimen of an abuser. AB - We experienced an autopsy case in which the cause of death was judged as poisoning by multiple new psychoactive substances, including AB-CHMINACA, 5 fluoro-AMB and diphenidine [Forensic Toxicol. 33 (2015): 45-53]. Although unchanged AB-CHMINACA could be detected from 8 solid tissues, it could neither be detected from blood nor urine specimens. In this article, we obtained eight kinds of reference standards of AB-CHMINACA metabolites from a commercial source. The AB-CHMINACA metabolites from the urine specimen of the abuser were extracted by a modified QuEChERS method and analyzed by liquid chromatography-tandem mass spectrometry before and after hydrolysis with beta-glucuronidase. Among the eight AB-CHMINACA metabolites tested, only 2 metabolites could be identified in the urine specimen of the deceased. After hydrolysis with beta-glucuronidase, the concentrations of the two metabolites were not increased, suggesting that the metabolites were not in the conjugated forms. The metabolites detected were 4 hydroxycyclohexylmethyl AB-CHMINACA (M1), followed by N-[[1-(cyclohexylmethyl)-1H indazol-3-yl]carbonyl]-l-valine (M3). Their concentrations were 52.8 +/- 3.44 and 41.3 +/- 5.04 ng/ml (n=10) for M1 and M3, respectively. Although there is one preceding report showing the estimations of metabolism of AB-CHMINACA without reference standards, this is the first report dealing with exact identification using reference standards, and quantification of M1 and M3 in an authentic urine specimen. PMID- 26257318 TI - De novo resistance biomarkers to anti-HER2 therapies in HER2-positive breast cancer. AB - Therapies targeting HER2 receptor, overexpressed in 20% breast cancer (BC), improved prognosis, however ~62% patients experiment progression during the first year. Molecular mechanisms proposed to be responsible for this de novo resistance include HER2 modifications, defects in the antibody dependent cellular cytotoxicity or in cell arrest and apoptosis or alterations in HER2 signaling components. This article will review the influence of genetic markers investigated to date as cause of de novo resistance to HER2-targeted drugs in HER2-positive BC patients. Biomarkers like p95HER2, CCND1 and CDC25A have demonstrated clinical relevance and prognostic value in HER2-positive BC patients. However, the prognostic value of most biomarkers investigated to date, such as PIK3CA or AKT1, cannot be fully established yet. PMID- 26257319 TI - Efficient pDNA Delivery Using Cationic 2-Hydroxypropyl-beta-Cyclodextrin Pluronic Based Polyrotaxanes. AB - A family of cationic Pluronic-based polyrotaxanes (PR(+)), threaded with 2 hydroxypropyl-beta-cyclodextrin (HPCD), was synthesized for pDNA delivery into multiple cell lines. All PR(+) formed highly stable, positively charged pDNA complexes that were < 250 nm in diameter. The cellular uptake and pDNA transfection efficiencies of the PR(+):pDNA complexes was enhanced relative to the commercial transfection standards L2K and bPEI, while displaying similar or lower toxicity profiles. Charge density and threading efficiency of the PR(+) agent significantly influenced the colloidal stability and physical properties of the complexes, which impacted their intracellular transfection efficiencies. Taken together, our results suggest that HPCD: Pluronic PR(+) can be used as potent vectors for pDNA-based therapeutics. PMID- 26257320 TI - The Erratic Behavior of Lesions in Burnt Bone. AB - This study analyses depressed fractures (by blunt force trauma) and circular full thickness injuries (drill injuries and gunshot wounds) in charred bones. Fifty bovine ribs (total 104 lesions) were divided into three groups. The first group consisted in 20 depressed hammer-produced fractures; in the second one, 60 round drill-holes were produced (30 circular, 30 semicircular); in the third group, 12 fleshed and 12 skeletonized ribs were hit by 9-mm bullets. Each specimen was carbonized in an electric oven up to 800 degrees C. Morphological and metric analyses were performed before and after: morphological features were preserved, but depressed fractures showed an increase in their dimensions (p-value<0.05); the drilled holes shrunk (p-value<0.01); the charring cycle increased the number of fractures in samples with gunshot wounds differently in fleshed and defleshed ribs. This study showed the complex behavior of charred bone, for what concerns the interpretation of trauma and how caution should be applied. PMID- 26257321 TI - Effects of physical and mental health on relationship satisfaction: a dyadic, longitudinal examination of couples facing prostate cancer. AB - OBJECTIVES: Prostate cancer may affect quality of life in men diagnosed as well as their spouses. Changes in health may disrupt the couple's relationship functioning which disrupts recovery. This study examined how mental and physical health relates to relationship satisfaction for couples at diagnosis through the year following treatment. METHODS: Patients with stage I-II prostate cancer and their spouses (N = 159 couples) were recruited from a urology clinic and completed questionnaires at diagnosis, 1 month, 6 months, and 12 months post prostatectomy on demographics, mental and physical health quality of life, and relationship satisfaction. The Actor-Partner Interdependence Model was employed to examine effects of each partners' mental and physical health on their own and their partner's relationship satisfaction. RESULTS: Patients and spouses had declined mental and physical health at 1 month post-surgery. Health improved at 6 and 12 months but did not fully return to pre-surgery levels. Actor effects showed that patient's physical health consistently predicted own relationship satisfaction. Both patient's and spouse's mental health consistently related to their own relationship satisfaction. Partner effects showed that patient's and spouse's physical health had an effect on each other's relationship satisfaction at 1 month. Spouse's mental health predicted patient's relationship satisfaction throughout the year following treatment. CONCLUSION: The effects of patient and spouse mental and physical health quality of life on their own as well as their partner's relationship satisfaction differed across time which will inform psychosocial interventions for couples with prostate cancer. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26257322 TI - Two faces of cannabis. PMID- 26257324 TI - Bolt Cutter Blade's Imprint in Toolmarks Examination. AB - Bolt cutters are known as cutting tools which are used for cutting hard objects and materials, such as padlocks and bars. Bolt cutter blades leave their imprint on the cut objects. When receiving a cut object from a crime scene, forensic toolmarks examiners can determine whether the suspected cutting tool was used in a specific crime or not based on class characteristic marks and individual marks that the bolt cutter blades leave on the cut object. The paper presents preliminary results of a study on ten bolt cutters and suggests a quick preliminary examination-the comparison between the blade thickness and the width of the imprint left by the tool on the cut object. Based on the comparison result, if there is not a match, the examiner can eliminate the feasibility of the use of the suspected cutting tool in a specific crime. This examination simplifies and accelerates the comparison procedure. PMID- 26257323 TI - Safety, efficacy and glucose turnover of reduced prandial boluses during closed loop therapy in adolescents with type 1 diabetes: a randomized clinical trial. AB - AIMS: To evaluate safety, efficacy and glucose turnover during closed-loop with meal announcement using reduced prandial insulin boluses in adolescents with type 1 diabetes (T1D). METHODS: We conducted a randomized crossover study comparing closed-loop therapy with standard prandial insulin boluses versus closed-loop therapy with prandial boluses reduced by 25%. Eight adolescents with T1D [3 males; mean (standard deviation) age 15.9 (1.5) years, glycated haemoglobin 74 (17) mmol/mol; median (interquartile range) total daily dose 0.9 (0.7, 1.1) IU/kg/day] were studied on two 36-h-long visits. In random order, subjects received closed-loop therapy with either standard or reduced insulin boluses administered with main meals (50-80 g carbohydrates) but not with snacks (15-30 g carbohydrates). Stable-label tracer dilution methodology measured total glucose appearance (Ra_total) and glucose disposal (Rd). RESULTS: The median (interquartile range) time spent in target (3.9-10 mmol/l) was similar between the two interventions [74 (66, 84)% vs 80 (65, 96)%; p = 0.87] as was time spent above 10 mmol/l [21.8 (16.3, 33.5)% vs 18.0 (4.1, 34.2)%; p = 0.87] and below 3.9 mmol/l [0 (0, 1.5)% vs 0 (0, 1.8)%; p = 0.88]. Mean plasma glucose was identical during the two interventions [8.4 (0.9) mmol/l; p = 0.98]. Hypoglycaemia occurred once 1.5 h post-meal during closed-loop therapy with standard bolus. Overall insulin delivery was lower with reduced prandial boluses [61.9 (55.2, 75.0) vs 72.5 (63.6, 80.3) IU; p = 0.01] and resulted in lower mean plasma insulin concentration [186 (171, 260) vs 252 (198, 336) pmol/l; p = 0.002]. Lower plasma insulin was also documented overnight [160 (136, 192) vs 191 (133, 252) pmol/l; p = 0.01, pooled nights]. Ra_total was similar [26.3 (21.9, 28.0) vs 25.4 (21.0, 29.2) umol/kg/min; p = 0.19] during the two interventions as was Rd [25.8 (21.0, 26.9) vs 25.2 (21.2, 28.8) umol/kg/min; p = 0.46]. CONCLUSIONS: A 25% reduction in prandial boluses during closed-loop therapy maintains similar glucose control in adolescents with T1D whilst lowering overall plasma insulin levels. It remains unclear whether closed-loop therapy with a 25% reduction in prandial boluses would prevent postprandial hypoglycaemia. PMID- 26257325 TI - Cancer services in Western Australia: A comparison of regional outcomes with metropolitan Perth. AB - OBJECTIVE: To investigate whether any survival differences existed between advanced cancer patients treated in metropolitan Perth and those treated in regional Western Australia (WA). DESIGN: Retrospective study. SETTING: Advanced cancer patients treated through medical oncology clinics at Royal Perth Hospital and regional cancer centres (Kalgoorlie, Albany, Geraldton and Northam). PARTICIPANTS: Patients diagnosed with advanced melanoma, breast, colorectal, gastro-oesophageal, prostate, lung and pancreatic cancers between 1 January 2007 and 31 December 2011. INTERVENTIONS: Nil. MAIN OUTCOME MEASURE: Median survival. RESULTS: Data were available for 1581 patients with 75% living in a metropolitan setting and 25% in rural WA. Median overall survival was 8.3 months for metropolitan patients and 7.6 months for regional patients (P = 0.06, HR 0.89; 95% CI, 0.78-1.01). There was no statistically significant difference in median survival for different tumour types except pancreatic cancer: breast 22.1 months versus 21.3 months, colorectal 13.1 months versus 16.4 months, lung 5.1 months versus 3.1 months, upper GI 5.6 months versus 7.2 months, pancreatic 4.5 months versus 3 months (P = 0.02, HR 0.57; 95% CI, 0.32-0.99), melanoma 10.4 months versus 10.5 months, prostate 28.6 months versus 15.3 months. Rural cancer patients with breast and pancreatic cancers received fewer lines of anti-cancer therapy compared to metropolitan patients. The three-year survival rates for metropolitan compared to rural breast cancer patients were 34 and 23%, respectively (not statistically significant). CONCLUSION: Our findings suggest a trend towards inferior survival for regional cancer patients in WA compared with metropolitan-based patients. PMID- 26257326 TI - Clinical study designs and corresponding levels of evidence: time to redefine? PMID- 26257327 TI - ESCP President's Report. PMID- 26257328 TI - Commentary on 'Navigating the mesentery: a comparative pre- and per-operative visualization of the vascular anatomy'. PMID- 26257333 TI - Biochemical characterization and selective inhibition of beta-carotene cis-trans isomerase D27 and carotenoid cleavage dioxygenase CCD8 on the strigolactone biosynthetic pathway. AB - The first three enzymatic steps of the strigolactone biosynthetic pathway catalysed by beta-carotene cis-trans isomerase Dwarf27 (D27) from Oryza sativa and carotenoid cleavage dioxygenases CCD7 and CCD8 from Arabidopsis thaliana have been reconstituted in vitro, and kinetic assays have been developed for each enzyme, in order to develop selective enzyme inhibitors. Recombinant OsD27 shows a UV-visible lambdamax at 422 nm and is inactivated by silver(I) acetate, consistent with the presence of an iron-sulfur cluster that is used in catalysis. OsD27 and AtCCD7 are not inhibited by hydroxamic acids that cause shoot branching in planta, but OsD27 is partially inhibited by terpene-like hydroxamic acids. The reaction catalysed by AtCCD8 is shown to be a two-step kinetic mechanism using pre-steady-state kinetic analysis. Kinetic evidence is presented for acid-base catalysis in the CCD8 catalytic cycle and the existence of an essential cysteine residue in the CCD8 active site. AtCCD8 is inhibited in a time-dependent fashion by hydroxamic acids D2, D4, D5 and D6 (> 95% inhibition at 100 MUm) that cause a shoot branching phenotype in A. thaliana, and selective inhibition of CCD8 is observed using hydroxamic acids D13H and D15 (82%, 71% inhibition at 10 MUm). The enzyme inhibition data imply that the biochemical basis of the shoot branching phenotype is due to inhibition of CCD8. PMID- 26257334 TI - Maturational alterations in constitutive activity of medial prefrontal cortex kappa-opioid receptors in Wistar rats. AB - Opioid receptors can display spontaneous agonist-independent G-protein signaling (basal signaling/constitutive activity). While constitutive kappa-opioid receptor (KOR) activity has been documented in vitro, it remains unknown if KORs are constitutively active in native systems. Using [(35) S] guanosine 5'-O-[gamma thio] triphosphate coupling assay that measures receptor functional state, we identified the presence of medial prefrontal cortex KOR constitutive activity in young rats that declined with age. Furthermore, basal signaling showed an age related decline and was insensitive to neutral opioid antagonist challenge. Collectively, the present data are first to demonstrate age-dependent alterations in the medial prefrontal cortex KOR constitutive activity in rats and changes in the constitutive activity of KORs can differentially impact KOR ligand efficacy. These data provide novel insights into the functional properties of the KOR system and warrant further consideration of KOR constitutive activity in normal and pathophysiological behavior. Opioid receptors exhibit agonist-independent constitutive activity; however, kappa-opioid receptor (KOR) constitutive activity has not been demonstrated in native systems. Our results confirm KOR constitutive activity in the medial prefrontal cortex (mPFC) that declines with age. With the ability to presynaptically inhibit multiple neurotransmitter systems in the mPFC, maturational or patho-logical alterations in constitutive activity could disrupt corticofugal glutamatergic pyramidal projection neurons mediating executive function. Regulation of KOR constitutive activity could serve as a therapeutic target to treat compromised executive function. PMID- 26257335 TI - The loop structure of Actinomycete glycoside hydrolase family 5 mannanases governs substrate recognition. AB - Endo-beta-1,4-mannanases from Streptomyces thermolilacinus (StMan) and Thermobifida fusca (TfMan) demonstrated different substrate specificities. StMan hydrolyzed galactosylmannooligosaccharide (GGM5; 6(III) ,6(IV) -alpha-d galactosyl mannopentaose) to GGM3 and M2, whereas TfMan hydrolyzed GGM5 to GGM4 and M1. To determine the region involved in the substrate specificity, we constructed chimeric enzymes of StMan and TfMan and evaluated their substrate specificities. Moreover, the crystal structure of the catalytic domain of StMan (StMandC) and the complex structure of the inactive mutant StE273AdC with M6 were solved at resolutions of 1.60 and 1.50 A, respectively. Structural comparisons of StMandC and the catalytic domain of TfMan lead to the identification of a subsite around -1 in StMandC that could accommodate a galactose branch. These findings demonstrate that the two loops (loop7 and loop8) are responsible for substrate recognition in GH5 actinomycete mannanases. In particular, Trp281 in loop7 of StMan, which is located in a narrow and deep cleft, plays an important role in its affinity toward linear substrates. Asp310 in loop8 of StMan specifically bound to the galactosyl unit in the -1 subsite. PMID- 26257336 TI - Systems biology approach to studying proliferation-dependent prognostic subnetworks in breast cancer. AB - Tumor proliferative capacity is a major biological correlate of breast tumor metastatic potential. In this paper, we developed a systems approach to investigate associations among gene expression patterns, representative protein protein interactions, and the potential for clinical metastases, to uncover novel survival-related subnetwork signatures as a function of tumor proliferative potential. Based on the statistical associations between gene expression patterns and patient outcomes, we identified three groups of survival prognostic subnetwork signatures (SPNs) corresponding to three proliferation levels. We discovered 8 SPNs in the high proliferation group, 8 SPNs in the intermediate proliferation group, and 6 SPNs in the low proliferation group. We observed little overlap of SPNs between the three proliferation groups. The enrichment analysis revealed that most SPNs were enriched in distinct signaling pathways and biological processes. The SPNs were validated on other cohorts of patients, and delivered high accuracy in the classification of metastatic vs non-metastatic breast tumors. Our findings indicate that certain biological networks underlying breast cancer metastasis differ in a proliferation-dependent manner. These networks, in combination, may form the basis of highly accurate prognostic classification models and may have clinical utility in guiding therapeutic options for patients. PMID- 26257337 TI - Polymorphisms in MicroRNA Genes And Genes Involving in NMDAR Signaling and Schizophrenia: A Case-Control Study in Chinese Han Population. AB - Disturbances in glutamate signaling caused by disruption of N-methyl-D-aspartate type glutamate receptor (NMDAR) have been implicated in schizophrenia. Findings suggested that miR-219, miR-132 and miR-107 could involve in NMDAR signaling by influencing the expression of pathway genes or the signaling transmission and single nucleotide polymorphisms (SNPs) within miRNA genes or miRNA target sites could result in their functional changes. Therefore, we hypothesized that SNPs in miRNAs and/or their target sites were associated with schizophrenia. 3 SNPs in hsa-pri-miR-219/132/107 and 6 SNPs in 3'UTRs of GRIN2A/2B/3A and CAMK2G were selected and genotyped in a case-control study of 1041 schizophrenia cases and 953 healthy controls in Chinese Han population. In the present study, GRIN2B rs890 showed significant associations with schizophrenia. Further functional analyses showed that the rs890 variant C allele led to significantly lower luciferase activity, compared with the A allele. MDR analysis showed that a 4 locus model including rs107822, rs2306327, rs890 and rs12342026 was the best model. These findings suggest that GRIN2B may be associated with schizophrenia and interaction effects of the polymorphisms in hsa-miR-219, CAKM2G, GRIN2B and GRIN3A may confer susceptibility to schizophrenia in the Chinese Han population. PMID- 26257338 TI - Periodontal healing with a preameloblast-conditioned medium in dogs. AB - BACKGROUND AND OBJECTIVE: The predictability of conventional periodontal treatments for damaged periodontal tissue is limited, particularly on the regeneration of new cementum. As signaling molecules, a range of growth factors has been used to promote periodontal regeneration on periodontal ligament (PDL) and cementum defects. A preameloblast-conditioned medium (PA-CM) was prepared from cultured murine apical bud cells, which can differentiate into ameloblasts. We examined the effect of PA-CM on PDL cells and cementoblasts in vitro and evaluated histologically the effects of PA-CM on the regeneration of experimentally induced periodontal defects in vivo. MATERIAL AND METHODS: In vitro, the effects of PA-CM on the migration of human PDL cells were examined using a scratch wound healing assay and a transwell assay. The differentiation and mineralization potential of PA-CM-treated human PDL cells and murine cementoblastic OCCM-30 cells was examined by real-time polymerase chain reaction and Alizarin red-S staining. In vivo, six mongrel dogs (12-16 kg; 6-8 mo old) were used. Twenty-four roots were replanted with either, (i) only periodontal defects (n = 12; control group), or (ii) periodontal defects and PA-CM treatment (n = 12; experimental group). In the experimental group, the PDL and cementum between notches was removed using a Gracey curette and soaked in 0.08 mL water containing 80 MUg of a PA-CM for 2 min. The dogs were killed at 4 and 8 wk post surgery. RESULTS: The in vitro results showed that PA-CM stimulated the migration of PDL cells and promoted the differentiation and mineralization of PDL cells and cementoblasts. Real-time polymerase chain reaction analysis revealed stronger expression of Runx2, Osx, OC, Bsp and Cap mRNAs in the PA-CM-treated PDL cells and cementoblasts than those in the control cells. In vivo, newly formed PDL-like tissue and cementum-like tissue were observed partially between the root surfaces and newly formed bone in the experimental group. The regenerated PDL-like tissue in the experimental group was significantly higher than that in the control group at 8 wk (p < 0.05). The replacement resorption on the experimental group was significantly lower than that in the control group at 8 wk (p < 0.05). In addition, the amount of newly formed cementum-like tissue in the experimental group was significantly higher than that in the control group at 4 and 8 wk (p < 0.05). CONCLUSION: These results suggest that PA-CM has the potential to regenerate periodontal tissues in PDL and cementum defects. PMID- 26257339 TI - Putative involvement of the nitrergic system on the consolidation, but not initiation, of behavioral sensitization after conspecific alarm substance in zebrafish. AB - Stressful manipulations can sensitize the behavior of an organism, increasing anxiety-like behavior after a delay; this long-term stress sensitization can represent the pathophysiological basis of trauma- and stress-related disorders (TRSDs), of which the most prevalent is post-traumatic stress disorder (PTSD). A role for the glutamate-nitric oxide pathway in this sensitization is implied by behavioral, neurophysiological and genomic data on different species. Here, we report on the long-term sensitization of anxiety-like behavior in zebrafish and the possible participation of nitric oxide in this process. Zebrafish exposed to a conspecific alarm substance (AS) show increased anxiety-like behavior at least 24h after stimulus delivery. Blocking nitric oxide synthesis with l-NAME (5mg/kg) 30min, but not 90min, after AS exposure blocks the sensitization of scototaxis and risk assessment, while treatment 90min after exposure blocks the sensitization of thigmotaxis and erratic swimming; l-NAME was not effective when administered 30min before AS exposure. These data suggest a participation of nitric oxide in the consolidation, but not in the initiation, of behavioral sensitization after predator threat. PMID- 26257340 TI - Ozone concentrations, flux and potential effect on yield during wheat growth in the Northwest-Shandong Plain of China. AB - Ozone (O3) concentration and flux (Fo) were measured using the eddy covariance technique over a wheat field in the Northwest-Shandong Plain of China. The O3 induced wheat yield loss was estimated by utilizing O3 exposure-response models. The results showed that: (1) During the growing season (7 March to 7 June, 2012), the minimum (16.1 ppbV) and maximum (53.3 ppbV) mean O3 concentrations occurred at approximately 6:30 and 16:00, respectively. The mean and maximum of all measured O3 concentrations were 31.3 and 128.4 ppbV, respectively. The variation of O3 concentration was mainly affected by solar radiation and temperature. (2) The mean diurnal variation of deposition velocity (Vd) can be divided into four phases, and the maximum occurred at noon (12:00). Averaged Vd during daytime (6:00-18:00) and nighttime (18:00-6:00) were 0.42 and 0.14 cm/sec, respectively. The maximum of measured Vd was about 1.5 cm/sec. The magnitude of Vd was influenced by the wheat growing stage, and its variation was significantly correlated with both global radiation and friction velocity. (3) The maximum mean Fo appeared at 14:00, and the maximum measured Fo was -33.5 nmol/(m(2).sec). Averaged Fo during daytime and nighttime were -6.9 and -1.5 nmol/(m(2).sec), respectively. (4) Using O3 exposure-response functions obtained from the USA, Europe, and China, the O3-induced wheat yield reduction in the district was estimated as 12.9% on average (5.5%-23.3%). Large uncertainties were related to the statistical methods and environmental conditions involved in deriving the exposure-response functions. PMID- 26257341 TI - Effect of orchard age on soil nitrogen transformation in subtropical China and implications. AB - A better understanding of nitrogen transformation in soils could reveal the capacity for biological inorganic N supply and improve the efficiency of N fertilizers. In this study, a (15)N tracing study was carried out to investigate the effects of converting woodland to orchard, and orchard age on the gross rates of N transformation occurring simultaneously in subtropical soils in Eastern China. The results showed that inorganic N supply rate was remained constant with soil organic C and N contents increased after converting woodland into citrus orchard and with increasing orchard age. This phenomenon was most probably due to the increase in the turnover time of recalcitrant organic-N, which increased with decreasing soil pH along with increasing orchard age significantly. The amoA gene copy numbers of both archaeal and bacterial were stimulated by orchard planting and increased with increasing orchard age. The nitrification capacity (defined as the ratio of gross rate of nitrification to total gross rate of mineralization) increased following the Michaelis-Menten equation, sharply in the first 10 years after woodland conversion to orchard, and increased continuously but much more slowly till 30 years. Due to the increase in nitrification capacity and unchanged NO3(-) consumption, the dominance of ammonium in inorganic N in woodland soil was shifted to nitrate dominance in orchard soils. These results indicated that the risk of NO3(-) loss was expected to increase and the amount of N needed from fertilizers for fruit growth did not change although soil organic N accumulated with orchard age. PMID- 26257342 TI - Comparisons of the film peeling from the composite oxides of quartz sand filters using ozone, hydrogen peroxide and chlorine dioxide. AB - To solve the problem of shortened backwashing intervals in groundwater plants, several disinfectants including ozone (O3), hydrogen peroxide (H2O2) and chlorine dioxide (ClO2) were examined to peel off the film from the quartz sand surface in four pilot-scale columns. An optimized oxidant dosage and oxidation time were determined by batch tests. Subsequently, the optimized conditions were tested in the four pilot-scale columns. The results demonstrated that the backwashing intervals increased from 35.17 to 54.33 (H2O2) and to 53.67 hr (ClO2) after the oxidation treatments, and the increase of backwashing interval after treatment by O3 was much less than for the other two treatments. Interestingly, the treatment efficiency of filters was not affected by O3 or H2O2 oxidation; but after oxidation by ClO2, the treatment efficiency was deteriorated, especially the ammonia removal (from 96.96% to 24.95%). The filter sands before and after the oxidation were characterized by scanning electron microscopy and X-ray photoelectron spectroscopy. Compared with the oxidation by O3 and H2O2, the structures on the surface of filter sands were seriously damaged after oxidation by ClO2. The chemical states of manganese on the surfaces of those treated sands were only changed by ClO2. The damage of the structures and the change of the chemical states of manganese might have a negative effect on the ammonia removal. In summary, H2O2 is a suitable agent for film peeling. PMID- 26257343 TI - The relationship between light intensity and nutrient uptake kinetics in six freshwater diatoms. AB - In order to find effective measures to control diatom blooms, a better understanding of the physiological characteristics of nutrient uptake in diatoms is needed. A study of P and Si-uptake kinetics for diatom species from two light regimes was conducted at low (LL), moderate (ML) and high light intensities (HL) (2, 25 and 80 MUmol photons/(m(2).sec)), respectively. The results showed that P uptake of diatoms was heavily influenced by historic light regimes. P affinity changed with growth and photosynthetic activity. The lowest half saturation constant for P uptake (Km(P)) was under HL for high-light adapted diatoms while the lowest half-saturation constant for low-light adapted diatoms was observed under LL. The Si half-saturation constant (Km(Si)) increased with increasing light intensities for pennate diatoms but decreased for centric diatoms. Diatom volumes were correlated with the maximum Si uptake rates (Vm(Si)) at HL and Km(Si) at ML and HL for six diatom species. Our results imply that when we assess the development of diatom blooms we should consider light intensity and cell volume in addition to ambient Si or P concentration. The relationship between light intensity and P-uptake suggests that we can find suitable methods to control diatom blooms on the basis of reducing phytoplankton activity of P-uptake and photosynthesis simultaneously. PMID- 26257344 TI - Regeneration performance and carbon consumption of semi-coke and activated coke for SO2 and NO removal. AB - To decrease the operating cost of flue gas purification technologies based on carbon-based materials, the adsorption and regeneration performance of low-price semi-coke and activated coke were compared for SO2 and NO removal in a simulated flue gas. The functional groups of the two adsorbents before and after regeneration were characterized by a Fourier transform infrared (FTIR) spectrometer, and were quantitatively assessed using temperature programmed desorption (TPD) coupled with FTIR and acid-base titration. The results show that semi-coke had higher adsorption capacity (16.2% for SO2 and 38.6% for NO) than activated coke because of its higher content of basic functional groups and lactones. After regeneration, the adsorption performance of semi-coke decreased because the number of active functional groups decreased and the micropores increased. Semi-coke had better regeneration performance than activated coke. Semi-coke had a larger SO2 recovery of 7.2% and smaller carbon consumption of 12% compared to activated coke. The semi-coke carbon-based adsorbent could be regenerated at lower temperatures to depress the carbon consumption, because the SO2 recovery was only reduced a small amount. PMID- 26257345 TI - Vertical distribution of aerosol optical properties based on aircraft measurements over the Loess Plateau in China. AB - Vertical distributions of aerosol optical properties based on aircraft measurements over the Loess Plateau were measured for the first time during a summertime aircraft campaign, 2013 in Shanxi, China. Data from four flights were analyzed. The vertical distributions of aerosol optical properties including aerosol scattering coefficients (sigmasc), absorption coefficients (sigmaab), Angstrom exponent (alpha), single scattering albedo (omega), backscattering ratio (betasc), aerosol mass scattering proficiency (Qsc) and aerosol surface scattering proficiency (Qsc(')) were obtained. The mean statistical values of sigmasc were 77.45 Mm(-1) (at 450 nm), 50.72 Mm(-1) (at 550n m), and 32.02 Mm(-1) (at 700 nm). The mean value of sigmaab was 7.62 Mm(-1) (at 550 nm). The mean values of alpha, betasc and omega were 1.93, 0.15, and 0.91, respectively. Aerosol concentration decreased with altitude. Most effective diameters (ED) of aerosols were less than 0.8 MUm. The vertical profiles of sigmasc,, alpha, betasc, Qsc and Qsc(') showed that the aerosol scattering properties at lower levels contributed the most to the total aerosol radiative forcing. Both alpha and betasc had relatively large values, suggesting that most aerosols in the observational region were small particles. The mean values of sigmasc, alpha, betasc, Qsc, Qsc('), sigmaab and omega at different height ranges showed that most of the parameters decreased with altitude. The forty-eight hour backward trajectories of air masses during the observation days indicated that the majority of aerosols in the lower level contributed the most to the total aerosol loading, and most of these particles originated from local or regional pollution emissions. PMID- 26257346 TI - Evaluating the blank contamination and recovery of sample pretreatment procedures for analyzing organophosphorus flame retardants in waters. AB - Organophosphate esters (OPEs), used as flame retardants and plasticizers, are widely present in environmental waters. Development of accurate determination methods for trace OPEs in water is urgent for understanding the fate and risk of this class of emerging pollutants. However, the wide use of OPEs in experimental materials results in blank interference, which influences the accuracy of analytical results. In the present work, blank contamination and recovery of pretreatment procedures for analysis of OPEs in water samples were systematically examined for the first time. Blank contaminations were observed in filtration membranes, glass bottles, solid phase extraction cartridges, and nitrogen blowing instruments. These contaminations could be as high as 6.4-64ng/L per treatment. Different kinds of membranes were compared in terms of contamination levels left after common glassware cleaning, and a special wash procedure was proposed to eliminate the contamination from membranes. Meanwhile, adsorption of highly hydrophobic OPEs on the inside wall of glass bottles was found to be 42.4%-86.1%, which was the primary cause of low recoveries and was significantly reduced by an additional washing step with acetonitrile. This work is expected to provide guidelines for the establishment of analysis methods for OPEs in aqueous samples. PMID- 26257347 TI - Synergistic effect of ozonation and ionizing radiation for PVA decomposition. AB - Ozonation and ionizing radiation are both advanced oxidation processes (AOPs) without chemical addition and secondary pollution. Also, the two processes' efficiency is determined by different pH conditions, which creates more possibilities for their combination. Importantly, the combined process of ozonation and ionizing radiation could be suitable for treating wastewaters with extreme pH values, i.e., textile wastewater. To find synergistic effects, the combined process of ozonation and ionizing radiation mineralization was investigated for degradation of polyvinyl alcohol (PVA) at different pH levels. A synergistic effect was found at initial pH in the range 3.0-9.4. When the initial pH was 3.0, the combined process of ozonation and ionizing radiation gave a PVA mineralization degree of 17%. This was 2.7 times the sum achieved by the two individual processes, and factors of 2.1 and 1.7 were achieved at initial pH of 7.0 and 9.4, respectively. The combined process of ozonation and ionizing radiation was demonstrated to be a feasible strategy for treatment of PVA containing wastewater. PMID- 26257348 TI - Breakthrough CO2 adsorption in bio-based activated carbons. AB - In this work, the effects of different methods of activation on CO2 adsorption performance of activated carbon were studied. Activated carbons were prepared from biochar, obtained from fast pyrolysis of white wood, using three different activation methods of steam activation, CO2 activation and Potassium hydroxide (KOH) activation. CO2 adsorption behavior of the produced activated carbons was studied in a fixed-bed reactor set-up at atmospheric pressure, temperature range of 25-65 degrees C and inlet CO2 concentration range of 10-30 mol% in He to determine the effects of the surface area, porosity and surface chemistry on adsorption capacity of the samples. Characterization of the micropore and mesopore texture was carried out using N2 and CO2 adsorption at 77 and 273 K, respectively. Central composite design was used to evaluate the combined effects of temperature and concentration of CO2 on the adsorption behavior of the adsorbents. The KOH activated carbon with a total micropore volume of 0.62 cm(3)/g and surface area of 1400 m(2)/g had the highest CO2 adsorption capacity of 1.8 mol/kg due to its microporous structure and high surface area under the optimized experimental conditions of 30 mol% CO2 and 25 degrees C. The performance of the adsorbents in multi-cyclic adsorption process was also assessed and the adsorption capacity of KOH and CO2 activated carbons remained remarkably stable after 50 cycles with low temperature (160 degrees C) regeneration. PMID- 26257349 TI - Structure and properties of Co-doped cryptomelane and its enhanced removal of Pb2+ and Cr3+ from wastewater. AB - Cryptomelane is a reactive Mn oxide and has been used in removal of heavy metal from wastewaters. Co-doped cryptomelane was synthesized by refluxing at ambient pressure and characterized by powder X-ray diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy and extended X-ray absorption fine structure spectroscopy, and its performances for removal of Pb(2+) and Cr(3+) from aqueous solutions were investigated. Co doping has a negligible effect on the structure and morphology of cryptomelane but increases the specific surface area and Mn average oxidation state. Mn and Co K-edge extended X-ray absorption fine structure spectroscopy (EXAFS) analysis shows that Co barely affects the atomic coordination environments of Mn, and distances of edge- and corner-sharing Co-Me (MeCo, Mn) pairs are shorter than those of the corresponding Mn-Me pairs, implying the replacement of framework Mn(III) by Co(III). These Co-doped cryptomelanes can quickly oxidize Cr(3+) to be HCrO4(-) and remove 45%-66% of the total Cr in the reaction systems by adsorption and fixation, and they have enhanced Pb(2+) adsorption capacities. Thus these materials are promising adsorbents for heavy metal remediation. The results demonstrate the design and modification of environmental friendly Mn oxide materials and can help us understand the interaction mechanisms of transition metals with Mn oxides. PMID- 26257350 TI - Ractopamine up take by alfalfa (Medicago sativa) and wheat (Triticum aestivum) from soil. AB - Ractopamine is a beta adrenergic agonist used as a growth promoter in swine, cattle and turkeys. To test whether ractopamine has the potential to accumulate in plants grown in contaminated soil, a greenhouse study was conducted with alfalfa (Medicago sativa) and wheat (Triticum aestivum) grown in two soils having different concentrations of organic matter (1.3% and 2.1%), amended with 0, 0.5, and 10 MUg/g of ractopamine. Plant growth ranged from 2.7 to 8.8 g dry weight (dw) for alfalfa, and 8.7 to 40 g dw for wheat and was generally greater in the higher organic matter content soil. The uptake of ractopamine in plant tissues ranged from non-detectable to 897 ng/g and was strongly dependent on soil ractopamine concentration across soil and plant tissue. When adjusted to the total fortified quantities, the amount of ractopamine taken up by the plant tissue was low, <0.01% for either soil. PMID- 26257351 TI - Effects of nitrogen dioxide and its acid mist on reactive oxygen species production and antioxidant enzyme activity in Arabidopsis plants. AB - Nitrogen dioxide (NO2) is one of the most common and harmful air pollutants. To analyze the response of plants to NO2 stress, we investigated the morphological change, reactive oxygen species (ROS) production and antioxidant enzyme activity in Arabidopsis thaliana (Col-0) exposed to 1.7, 4, 8.5, and 18.8 mg/m(3) NO2. The results indicate that NO2 exposure affected plant growth and chlorophyll (Chl) content, and increased oxygen free radical (O2(-)) production rate in Arabidopsis shoots. Furthermore, NO2 elevated the levels of lipid peroxidation and protein oxidation, accompanied by the induction of antioxidant enzyme activities and change of ascorbate (AsA) and glutathione (GSH) contents. Following this, we mimicked nitric acid mist under experimental conditions, and confirmed the antioxidant mechanism of the plant to the stress. Our results imply that NO2 and its acid mist caused pollution risk to plant systems. During the process, increased ROS acted as a signal to induce a defense response, and antioxidant status played an important role in plant protection against NO2/nitric acid mist caused oxidative damage. PMID- 26257352 TI - Mechanism and kinetics of aluminum dissolution during copper sorption by acidity paddy soil in South China. AB - Soil aggregates were prepared from a bulk soil collected from paddy soil in the Taihu Lake region and aluminum (Al) dissolution, solution pH changes during copper (Cu(2+)) sorption were investigated with static sorption and magnetic stirring. Kinetics of Cu(2+) sorption and Al dissolution were also studied by magnetic stirring method. No Al dissolution was observed until Cu(2+) sorption was greater than a certain value, which was 632, 450, 601 and 674 mg/kg for sand, clay, silt, and coarse silt fractions, respectively. Aluminum dissolution increased with increasing Cu(2+) sorption and decreasing solution pH. An amount of dissolved Al showed a significant positive correlation with non-specific sorption of Cu(2+) (R(2)>0.97), and it was still good under different pH values (R(2)>0.95). Copper sorption significantly decreased solution pH. The magnitude of solution pH decline increased as Cu(2+) sorption and Al dissolution increased. The sand and clay fraction had a less Al dissolution and pH drop due to the higher ferric oxide, Al oxide and organic matter contents. After sorption reaction for half an hour, the Cu(2+) sorption progress reached more than 90% while the Al dissolution progress was only 40%, and lagged behind the Cu(2+) sorption. It indicated that aluminum dissolution is associated with non-specific sorption. PMID- 26257353 TI - Mercury levels and estimated total daily intakes for children and adults from an electronic waste recycling area in Taizhou, China: Key role of rice and fish consumption. AB - In order to assess the potential health risks of Hg pollution, total mercury (T Hg) and methyl mercury (MeHg) concentrations were determined in air, dust, surface soil, crops, poultry, fish and human hair samples from an electronic waste (e-waste) recycling area in Taizhou, China. High concentrations of T-Hg and MeHg were found in these multiple matrices, and the mean concentration was 30.7 ng/m(3) of T-Hg for atmosphere samples, 3.1 MUg/g of T-Hg for soil, 37.6 MUg/g of T-Hg for dust, 20.3 ng/g of MeHg for rice and 178.1 ng/g of MeHg for fish, suggesting that the e-waste recycling facility was a significant source of Hg. The inorganic Hg (I-Hg) levels (0.84 MUg/g) in hair samples of e-waste workers were much higher than that in the reference samples. Pearson's correlation coefficients showed that strong positive correlations (p<0.01) between hair I-Hg and time staying in industrial area (r=0.81) and between MeHg and fish consumption frequency (r=0.91), imply that workers were mainly exposed to Hg vapor through long-time inhalation of contaminated air and dust, while other population mainly exposed to MeHg through high-frequency fish consumption. The estimated daily intakes of Hg showed that dietary intake was the major Hg exposure source, and Hg intakes from rice and fish were significantly higher than from any other foods. The estimated total daily intakes (TDIs) of MeHg for both children (696.8 ng/(kg.day)) and adults (381.3 ng/(kg.day)) greatly exceeded the dietary reference dose (RfD) of 230 ng/(kg.day), implying greater health risk for humans from Hg exposures around e-waste recycling facilities. PMID- 26257354 TI - Water chemistry controlled aggregation and photo-transformation of silver nanoparticles in environmental waters. AB - The inevitable release of engineered silver nanoparticles (AgNPs) into aquatic environments has drawn great concerns about its environmental toxicity and safety. Although aggregation and transformation play crucial roles in the transport and toxicity of AgNPs, how the water chemistry of environmental waters influences the aggregation and transformation of engineered AgNPs is still not well understood. In this study, the aggregation of polyvinylpyrrolidone (PVP) coated AgNPs was investigated in eight typical environmental water samples (with different ionic strengths, hardness, and dissolved organic matter (DOM) concentrations) by using UV-visible spectroscopy and dynamic light scattering. Raman spectroscopy was applied to probe the interaction of DOM with the surface of AgNPs. Further, the photo-transformation and morphology changes of AgNPs in environmental waters were studied by UV-visible spectroscopy, inductively coupled plasma mass spectrometry, and transmission electron microscopy. The results suggested that both electrolytes (especially Ca(2+) and Mg(2+)) and DOM in the surface waters are key parameters for AgNP aggregation, and sunlight could accelerate the morphology change, aggregation, and further sedimentation of AgNPs. This water chemistry controlled aggregation and photo-transformation should have significant environmental impacts on the transport and toxicity of AgNPs in the aquatic environments. PMID- 26257355 TI - Biodegradation of indole by a newly isolated Cupriavidus sp. SHE. AB - Indole, a typical nitrogen heterocyclic aromatic pollutant, is extensively spread in industrial wastewater. Microbial degradation has been proven to be a feasible approach to remove indole, whereas the microbial resources are fairly limited. A bacterial strain designated as SHE was isolated and found to be an efficient indole degrader. It was identified as Cupriavidus sp. according to 16S rRNA gene analysis. Strain SHE could utilize indole as the sole carbon source and almost completely degrade 100mg/L of indole within 24hr. It still harbored relatively high indole degradation capacity within pH4-9 and temperature 25 degrees C-35 degrees C. Experiments also showed that some heavy metals such as Mn(2+), Pb(2+) and Co(2+) did not pose severe inhibition on indole degradation. Based on high performance liquid chromatography-mass spectrum analysis, isatin was identified as a minor intermediate during the process of indole biodegradation. A major yellow product with m/z 265.0605 (C15H8N2O3) was generated and accumulated, suggesting a novel indole conversion pathway existed. Genome analysis of strain SHE indicated that there existed a rich set of oxidoreductases, which might be the key reason for the efficient degradation of indole. The robust degradation ability of strain SHE makes it a promising candidate for the treatment of indole containing wastewater. PMID- 26257356 TI - Use of Fe/Al drinking water treatment residuals as amendments for enhancing the retention capacity of glyphosate in agricultural soils. AB - Fe/Al drinking water treatment residuals (WTRs), ubiquitous and non-hazardous by products of drinking water purification, are cost-effective adsorbents for glyphosate. Given that repeated glyphosate applications could significantly decrease glyphosate retention by soils and that the adsorbed glyphosate is potentially mobile, high sorption capacity and stability of glyphosate in agricultural soils are needed to prevent pollution of water by glyphosate. Therefore, we investigated the feasibility of reusing Fe/Al WTR as a soil amendment to enhance the retention capacity of glyphosate in two agricultural soils. The results of batch experiments showed that the Fe/Al WTR amendment significantly enhanced the glyphosate sorption capacity of both soils (p<0.001). Up to 30% of the previously adsorbed glyphosate desorbed from the non-amended soils, and the Fe/Al WTR amendment effectively decreased the proportion of glyphosate desorbed. Fractionation analyses further demonstrated that glyphosate adsorbed to non-amended soils was primarily retained in the readily labile fraction (NaHCO3-glyphosate). The WTR amendment significantly increased the relative proportion of the moderately labile fraction (HCl-glyphosate) and concomitantly reduced that of the NaHCO3-glyphosate, hence reducing the potential for the release of soil-adsorbed glyphosate into the aqueous phase. Furthermore, Fe/Al WTR amendment minimized the inhibitory effect of increasing solution pH on glyphosate sorption by soils and mitigated the effects of increasing solution ionic strength. The present results indicate that Fe/Al WTR is suitable for use as a soil amendment to prevent glyphosate pollution of aquatic ecosystems by enhancing the glyphosate retention capacity in soils. PMID- 26257357 TI - A screening assay for thyroid hormone signaling disruption based on thyroid hormone-response gene expression analysis in the frog Pelophylax nigromaculatus. AB - Amphibian metamorphosis provides a wonderful model to study the thyroid hormone (TH) signaling disrupting activity of environmental chemicals, with Xenopus laevis as the most commonly used species. This study aimed to establish a rapid and sensitive screening assay based on TH-response gene expression analysis using Pelophylax nigromaculatus, a native frog species distributed widely in East Asia, especially in China. To achieve this, five candidate TH-response genes that were sensitive to T3 induction were chosen as molecular markers, and T3 induction was determined as 0.2 nmol/L T3 exposure for 48 hr. The developed assay can detect the agonistic activity of T3 with a lowest observed effective concentration of 0.001 nmol/L and EC50 at around 0.118-1.229 nmol/L, exhibiting comparable or higher sensitivity than previously reported assays. We further validated the efficiency of the developed assay by detecting the TH signaling disrupting activity of tetrabromobisphenol A (TBBPA), a known TH signaling disruptor. In accordance with previous reports, we found a weak TH agonistic activity for TBBPA in the absence of T3, whereas a TH antagonistic activity was found for TBBPA at higher concentrations in the presence of T3, showing that the P. nigromaculatus assay is effective for detecting TH signaling disrupting activity. Importantly, we observed non-monotonic dose-dependent disrupting activity of TBBPA in the presence of T3, which is difficult to detect with in vitro reporter gene assays. Overall, the developed P. nigromaculatus assay can be used to screen TH signaling disrupting activity of environmental chemicals with high sensitivity. PMID- 26257358 TI - Disruption of iron homeostasis and resultant health effects upon exposure to various environmental pollutants: A critical review. AB - Environmental pollution has become one of the greatest problems in the world, and the concerns about environmental pollutants released by human activities from agriculture and industrial production have been continuously increasing. Although intense efforts have been made to understand the health effects of environmental pollutants, most studies have only focused on direct toxic effects and failed to simultaneously evaluate the long-term adaptive, compensatory and secondary impacts on health. Burgeoning evidence suggests that environmental pollutants may directly or indirectly give rise to disordered element homeostasis, such as for iron. It is crucially important to maintain concerted cellular and systemic iron metabolism. Otherwise, disordered iron metabolism would lead to cytotoxicity and increased risk for various diseases, including cancers. Thus, study on the effects of environmental pollutants upon iron homeostasis is urgently needed. In this review, we recapitulate the available findings on the direct or indirect impacts of environmental pollutants, including persistent organic pollutants (POPs), heavy metals and pesticides, on iron homeostasis and associated adverse health problems. In view of the unanswered questions, more efforts are warranted to investigate the disruptive effects of environmental pollutants on iron homeostasis and consequent toxicities. PMID- 26257359 TI - Effects of chronic and subtoxic chlorobenzenes on adrenocorticotrophic hormone release. AB - Many environmental chemicals and pesticides have been found to alter neuroendocrine communication in exposed biological objects. The environmental loads have primary and secondary effects that can alter the homeostatic regulation potential. Since it is difficult to avoid human exposition, a potentially important area of research to develop in vivo and in vitro experimental models. In this context, the primary aim of this study was to demonstrate the effects of chlorobenzenes on adrenocorticotrophic hormone (ACTH) release. In our experimental study, male Wistar rats were exposed to 0.1, 1.0 and 10 MUg/b.w. (body weight)kg of 1,2,4- trichlorobenzene and hexachlorobenzene (ClB) mix via gastric tube for 30, 60 or 90 days. At the endpoints of the experiment blood samples were taken and animals were decapitated. Primary, monolayer adenohypophysis cell cultures were prepared by enzymatic and mechanical digestion. The ACTH hormone content in serum and supernatant media was measured by immuno-chemiluminescence assay. The Mg(2+)-dependent ATPase activity was determined by modified method of Martin and Dotty. Significant differences were detected in the hormone release between the control and treated groups. The hormone release was enhanced characteristically in exposed groups depending upon the dose and duration of exposure. The Mg(2+)-ATPase activity enhanced after chronic and subtoxic ClB exposition. Light microscopy revealed that the adenohypophysis seemed to be more abundant. Results indicate that Wistar rats exposed to subtoxic ClB have direct and indirect effects on hypothalamus hypophysis-adrenal axis. PMID- 26257360 TI - Characterizations of organic compounds in diesel exhaust particulates. AB - To characterize how the speed and load of a medium-duty diesel engine affected the organic compounds in diesel particle matter (PM) below 1 MUm, four driving conditions were examined. At all four driving conditions, concentration of identifiable organic compounds in PM ultrafine (34-94 nm) and accumulation (94 1000 nm) modes ranged from 2.9 to 5.7 MUg/m(3) and 9.5 to 16.4 MUg/m(3), respectively. As a function of driving conditions, the non-oxygen-containing organics exhibited a reversed concentration trend to the oxygen-containing organics. The identified organic compounds were classified into eleven classes: alkanes, alkenes, alkynes, aromatic hydrocarbons, carboxylic acids, esters, ketones, alcohols, ethers, nitrogen-containing compounds, and sulfur-containing compounds. At all driving conditions, alkane class consistently showed the highest concentration (8.3 to 18.0 MUg/m(3)) followed by carboxylic acid, esters, ketones and alcohols. Twelve polycyclic aromatic hydrocarbons (PAHs) were identified with a total concentration ranging from 37.9 to 174.8 ng/m(3). In addition, nine nitrogen-containing polycyclic aromatic compounds (NPACs) were identified with a total concentration ranging from 7.0 to 10.3 ng/m(3). The most abundant PAH (phenanthrene) and NPACs (7,8-benzoquinoline and 3 nitrophenanthrene) comprise a similar molecular (3 aromatic-ring) structure under the highest engine speed and engine load. PMID- 26257361 TI - Interactive response of photosynthetic characteristics in Haloxylon ammodendron and Hedysarum scoparium exposed to soil water and air vapor pressure deficits. AB - C4 plants possess better drought tolerance than C3 plants. However, Hedysarum scoparium, a C3 species, is dominant and widely distributed in the desert areas of northwestern China due to its strong drought tolerance. This study compared it with Haloxylon ammodendron, a C4 species, regarding the interactive effects of drought stress and different leaf-air vapor pressure deficits. Variables of interest included gas exchange, the activity levels of key C4 photosynthetic enzymes, and cellular anatomy. In both species, gas exchange parameters were more sensitive to high vapor pressure deficit than to strong water stress, and the net CO2 assimilation rate (An) was enhanced as vapor pressure deficits increased. A close relationship between An and stomatal conductance (gs) suggested that the species shared a similar response mechanism. In H. ammodendron, the activity levels of key C4 enzymes were higher, including those of phosphoenolpyruvate carboxylase (PEPC) and nicotinamide adenine dinucleotide phosphate-malate enzyme (NADP-ME), whereas in H. scoparium, the activity level of nicotinamide adenine dinucleotide-malate enzyme (NAD-ME) was higher. Meanwhile, H. scoparium utilized adaptive structural features, including a larger relative vessel area and a shorter distance from vein to stomata, which facilitated the movement of water. These findings implied that some C4 biochemical pathways were present in H. scoparium to respond to environmental challenges. PMID- 26257362 TI - Seasonal variations and size distributions of water-soluble ions in atmospheric aerosols in Beijing, 2012. AB - The characteristics of water-soluble ions in airborne particulate matter in Beijing were investigated using ion chromatography. The results showed that the total concentrations of ions were 83.7 +/- 48.9 MUg/m(3) in spring, 54.0 +/- 17.0 MUg/m(3) in summer, 54.1 +/- 42.9 MUg/m(3) in autumn, and 88.8 +/- 47.7 MUg/m(3) in winter, respectively. Furthermore, out of all the ions, NO3(-), SO4(2-) and NH4(+) accounted for 81.2% in spring, 78.5% in summer, 74.6% in autumn, and 76.3% in winter. Mg(2+) and Ca(2+) were mainly associated with coarse particles, with a peak that ranged from 5.8 to 9.0 MUm. Na(+), NH4(+) and Cl(-) had a multi-mode distribution with peaks that ranged from 0.43 to 1.1 MUm and 4.7 to 9.0 MUm. K(+), NO3(-), and SO4(2-) were mainly associated with fine particles, with a peak that ranged from 0.65 to 2.1 MUm. The concentrations of Na(+), K(+), Mg(2+), Ca(2+), NH4(+), Cl(-), NO3(-) and SO4(2-) were 2.69, 2.32, 1.01, 4.84, 16.9, 11.8, 42.0, and 44.1 MUg/m(3) in particulate matter (PM) on foggy days, respectively, which were 1.4 to 7.3 times higher than those on clear days. The concentrations of these ions were 2.40, 1.66, 0.92, 4.95, 17.5, 7.00, 32.6, and 34.7 MUg/m(3) in PM on hazy days, respectively, which were 1.2-5.7 times higher than those on clear days. PMID- 26257363 TI - Trends of the sunshine duration and diffuse radiation percentage on sunny days in urban agglomerations of China during 1960-2005. AB - The long-term observational data of sunshine duration (SD) and diffuse radiation percentage (defined as diffuse solar radiation/total solar radiation, DRP) on sunny days during 1960-2005 were analyzed in 7 urban agglomerations and the whole of China. The results show that the sunny sunshine duration (SSD) has decreased significantly except at a few stations over northwestern China in the past 46 years. An obvious decrease of the SSD is found in eastern China, with the trend coefficients lower than -0.8. Accompanied by the SSD decline, the sunny diffuse radiation percentage (SDRP) in most stations shows obvious increasing trends during the 46 years. The averaged SDRP over China has increased 2.33% per decade, while the averaged SSD shows a decrease of -0.13 hr/day per decade. The correlation coefficient between SDRP and SSD is -0.88. SSD decreased over urban agglomerations (small to large city clusters) in the past 46 years, especially in large cities and medium cities, due to the strong anthropogenic activities and air pollution represented by aerosol option depth (AOD) and tropospheric column NO2 (TroNO2). On the regional scale, SSD has an opposite trend from SDRP during 1960 to 2005, and the variation trends of regional mean values of SSD and SDRP in southeastern China are more pronounced than those in northwestern China. PMID- 26257364 TI - Determination of the cellulase activity distribution in Clostridium thermocellum and Caldicellulosiruptor obsidiansis cultures using a fluorescent substrate. AB - This study took advantage of resorufin cellobioside as a fluorescent substrate to determine the distribution of cellulase activity in cellulosic biomass fermentation systems. Cellulolytic biofilms were found to express nearly four orders greater cellulase activity compared to planktonic cultures of Clostridium thermocellum and Caldicellulosiruptor obsidiansis, which can be primarily attributed to the high cell concentration and surface attachment. The formation of biofilms results in cellulases being secreted close to their substrates, which appears to be an energetically favorable stategy for insoluble substrate utilization. For the same reason, cellulases should be closely associated with the surfaces of suspended cell in soluble substrate-fed culture, which has been verified with cellobiose-fed cultures of C. thermocellum and C. obsidiansis. This study addressed the importance of cellulase activity distribution in cellulosic biomass fermentation, and provided theoretical foundation for the leading role of biofilm in cellulose degradation. System optimization and reactor designs that promote biofilm formation in cellulosic biomass hydrolysis may promise an improved cellulosic biofuel process. PMID- 26257365 TI - Origin of high particle number concentrations reaching the St. Louis, Midwest Supersite. AB - Ultrafine particles are associated with adverse health effects. Total Particle Number Concentration (TNC) of fine particles were measured during 2002 at the St. Louis - Midwest supersite. The time series showed overall low level with frequent large peaks. The time series was analyzed alongside criteria pollutant measurements and meteorological observations. Multiple regression analysis was used to identify further contributing factors and to determine the association of different pollutants with TNC levels. This showed the strong contribution of sulfur dioxide (SO2) and nitrogen oxides (NOx) to high TNC levels. The analysis also suggested that increased dispersion resulting from faster winds and higher mixing heights led to higher TNC levels. Overall, the results show that there were intense particle nucleation events in a SO2 rich plume reaching the site which contributed around 29% of TNC. A further 40% was associated with primary emissions from mobile sources. By separating the remaining TNC by time of day and clear sky conditions, we suggest that most likely 8% of TNC are due to regional nucleation events and 23% are associated with the general urban background. PMID- 26257366 TI - Advances in photocatalytic disinfection of bacteria: Development of photocatalysts and mechanisms. AB - Photocatalysis has attracted worldwide attention due to its potential in solar energy conversion. As a "green" advanced oxidation technology, it has been extensively used for water disinfection and wastewater treatment. This article provides a review of the recent progress in solar energy-induced photocatalytic disinfection of bacteria, focusing on the development of highly efficient photocatalysts and their underlying mechanisms in bacterial inactivation. The photocatalysts are classified into TiO2-based and non-TiO2-based systems, as TiO2 is the most investigated photocatalyst. The synthesis methods, modification strategies, bacterial disinfection activities and mechanisms of different types of photocatalysts are reviewed in detail. Emphasis is given to the modified TiO2, including noble metal deposition, non-metal doping, dye sensitization and composite TiO2, along with typical non-TiO2-based photocatalysts for bacterial disinfection, including metal oxides, sulfides, bismuth metallates, graphene based photocatalysts, carbon nitride-based photocatalysts and natural photocatalysts. A simple and versatile methodology by using a partition system combined with scavenging study is introduced to study the photocatalytic disinfection mechanisms in different photocatalytic systems. This review summarizes the current state of the work on photocatalytic disinfection of bacteria, and is expected to offer useful insights for the future development in the field. PMID- 26257367 TI - Hydrothermal fabrication of selectively doped organic assisted advanced ZnO nanomaterial for solar driven photocatalysis. AB - Hydrothermal fabrication of selectively doped (Ag(+)+Pd(3+)) advanced ZnO nanomaterial has been carried out under mild pressure temperature conditions (autogeneous; 150 degrees C). Gluconic acid has been used as a surface modifier to effectively control the particle size and morphology of these ZnO nanoparticles. The experimental parameters were tuned to achieve optimum conditions for the synthesis of selectively doped ZnO nanomaterials with an experimental duration of 4 hr. These selectively doped ZnO nanoparticles were characterized using powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), UV-Vis spectroscopy and scanning electron microscopy (SEM). The solar driven photocatalytic studies have been carried out for organic dyes, i.e., Procion MX-5B dye, Cibacron Brilliant Yellow dye, Indigo Carmine dye, separately and all three mixed, by using gluconic acid modified selectively doped advanced ZnO nanomaterial. The influence of catalyst, its concentration and initial dye concentration resulted in the photocatalytic efficiency of 89% under daylight. PMID- 26257368 TI - New insights into disruption of iron homeostasis by environmental pollutants. AB - Among the numerous health conditions environmental pollutants can cause, chronic exposure to pollutants including persistent organic pollutants (POPs) and heavy metals has been shown to disturb a specific biological homeostatic process, the iron metabolism in human body. Disorders of iron metabolism are among the common diseases of humans and encompass a broad spectrum of diseases with different clinical manifestations, ranging from anemia to iron overload, and possibly to neurodegenerative diseases and cancer. Hepcidin-ferroportin (FPN) signaling is one of the key mechanisms responsible for iron supply, utilization, recycling, and storage, and recent studies demonstrated that exposure to environmental pollutants including POPs and heavy metals could lead to disruption of the hepcidin-FPN axis along with disordered systemic iron homeostasis and diseases. This article introduces and highlights the accompanying review article by Drs. Xu and Liu in this journal, which elaborates in detail the adverse effects of environmental pollutants on iron metabolism, and the mechanisms responsible for these toxicological outcomes. It also points out the knowledge gaps still existing in this subject matter. Research that will fill these gaps will improve our understanding of the issue and provide useful information to prevent or treat diseases induced by environmental pollutants. PMID- 26257369 TI - Is there a silver lining? Aggregation and photo-transformation of silver nanoparticles in environmental waters. PMID- 26257370 TI - High frequency of deficient consumption and low blood levels of 25-hydroxyvitamin D in HIV-1-infected adults from Sao Paulo city, Brazil. AB - Micronutrient deficiency is common in patients with HIV/AIDS, usually caused by mal-absorption and/or drug interactions. 25-hydroxyvitamin D is of fundamental importance for the homeostasis of musculoskeletal health. The current study aimed to evaluate the nutritional status of HIV-infected subjects in order to make their nutritional diagnoses, including their vitamin D blood levels, and to estimate their consumption of vitamin D. The study included 98 HIV-1-infected subjects, followed at University of Sao Paulo Medical School - HC-FMUSP. We performed a nutritional evaluation, along with the determination of patients' serum 25-hydroxyvitamin D and calcium concentration, biochemical analyses, and an anthropometric assessment. In the medical interview a 24-hour food recall was used (R24) to estimate daily calorie intake, macronutrients, calcium, and vitamin D. A high level of vitamin D deficiency was observed in our patients: 83.4% of them had levels below 30 ng/ml; they also presented an increased risk of cardiovascular disease, along with a high consumption of dietary fat. Factors related to the virus itself and to the use of antiretroviral drugs may have contributed for the low vitamin D levels seen in our HIV-1-infected patients. PMID- 26257371 TI - Association between parental history of diabetes and the incidence of type 2 diabetes mellitus differs according to the sex of the parent and offspring's body weight: A finding from a Japanese worksite-based cohort study. AB - OBJECTIVE: To investigate differences in the association of parental history of diabetes with the risk of type 2 diabetes mellitus (T2DM) in the offspring according to the sex of the parent and the offspring's body weight. METHODS: A prospective cohort study of 4446 middle-aged non-diabetic Japanese men and women were followed in Aichi Prefecture, central Japan, from 2002 to 2011. Subjects were categorized by their self-reported parental history of diabetes ("no parental history," "father only," "mother only," and "both"). The association of parental history of diabetes and incidence in the offspring was examined according to overweight status adjusted for age, sex, birth weight, smoking, alcohol consumption, physical activity, total energy intake, body mass index, and number of metabolic syndrome components. RESULTS: During follow-up (median 8.9 years), 277 subjects developed T2DM. Parental history of diabetes was positively associated with T2DM incidence. However, stratified analysis by overweight status revealed that only maternal history was associated with increased T2DM incidence in non-overweight subjects (hazard ratio=2.35, 95% confidence interval: 1.41 3.91). While in overweight subjects, paternal history was significantly associated with higher T2DM incidence (hazard ratio=1.98, 95% confidence interval: 1.19-3.28). CONCLUSIONS: Our results suggest that parental history of diabetes mellitus is associated with the incidence of T2DM in offspring differently according to the sex of the affected parent and the offspring's body weight. PMID- 26257372 TI - Editorial: 2nd Special Issue on behavior change, health, and health disparities. AB - This Special Issue of Preventive Medicine (PM) is the 2nd that we have organized on behavior change, health, and health disparities. This is a topic of fundamental importance to improving population health in the U.S. and other industrialized countries that are trying to more effectively manage chronic health conditions. There is broad scientific consensus that personal behavior patterns such as cigarette smoking, other substance abuse, and physical inactivity/obesity are among the most important modifiable causes of chronic disease and its adverse impacts on population health. As such behavior change needs to be a key component of improving population health. There is also broad agreement that while these problems extend across socioeconomic strata, they are overrepresented among more economically disadvantaged populations and contribute directly to the growing problem of health disparities. Hence, behavior change represents an essential step in curtailing that unsettling problem as well. In this 2nd Special Issue, we devote considerable space to the current U.S. prescription opioid addiction epidemic, a crisis that was not addressed in the prior Special Issue. We also continue to devote attention to the two largest contributors to preventable disease and premature death, cigarette smoking and physical inactivity/obesity as well as risks of co-occurrence of these unhealthy behavior patterns. Across each of these topics we included contributions from highly accomplished policy makers and scientists to acquaint readers with recent accomplishments as well as remaining knowledge gaps and challenges to effectively managing these important chronic health problems. PMID- 26257374 TI - Synthesis of new saccharide azacrown cryptands. AB - New cryptands including bis-azacrown and saccharidic moieties in their structure were prepared in several steps by applying Staudinger-aza-Wittig reaction (SAW). Syntheses have been started from cheap, easily available commercial compounds such as D-glucose, D-cellobiose and D-lactose subsequently transformed into their derivatives in fairly good yields (60-65%) and suitable to give desired final cryptands by direct SAW coupling reactions. PMID- 26257373 TI - White matter alterations in first episode treatment-naive patients with deficit schizophrenia: a combined VBM and DTI study. AB - Categorizing 'deficit schizophrenia' (DS) as distinct from 'non-deficit' schizophrenia (NDS) may help reduce heterogeneity within schizophrenia. However, it is unknown if DS has a discrete white matter signature. Here we used MRI to compare white matter volume (voxel-based morphometry) and microstructural integrity (fractional anisotropy, FA) in first-episode treatment-naive patients with DS and NDS and their unaffected relatives to control groups of similar age. We found that white matter disruption was prominent in DS compared to controls; the DS group had lower volumes in the cerebellum, bilateral extra-nuclear and bilateral frontoparietal regions, and lower FA in the body of corpus callosum, posterior superior longitudinal fasciculus and uncinate fasciculus. The DS group also had lower volume in bilateral extra-nuclear regions compared to NDS, and the volume of these clusters was negatively correlated with deficit symptom ratings. NDS patients however, had no significant volume alterations and limited disruption of microstructural integrity compared to controls. Finally, first degree relatives of those with DS shared volume abnormalities in right extra nuclear white matter. Thus, white matter pathology in schizophrenia is most evident in the deficit condition, and lower extra-nuclear white matter volumes in both DS patients and their relatives may represent a brain structural 'endophenotype' for DS. PMID- 26257375 TI - The O-specific polysaccharide from the marine bacterium Pseudoalteromonas agarivorans KMM 255(T). AB - The O-specific polysaccharide was isolated from the lipopolysaccharide of a marine bacterium Pseudoalteromonas agarivorans KMM 255(T) and studied by chemical methods along with (1)H and (13)C NMR spectroscopies. The following new structure of the O-specific polysaccharide from P. agarivorans KMM 255(T) containing 2 acetamido-2-deoxy-D-glucose (D-GlcNAc), D-glucose (D-Glc), D-glucuronic acid (D GlcA) and two residues of D-galactose (D-Gal) was established: Formula: see text]. PMID- 26257376 TI - Synthesis of four (4"-, 2"-, 2'-, and 6-) monodeoxy analogs of the trisaccharide alpha-D-Glcp-(1 -> 3)-alpha-D-Manp-(1 -> 2)-alpha-D-ManpOMe recognized by Calreticulin/Calnexin. AB - Routes for efficient synthesis of four (4"-, 2"-, 2'-, and 6-) monodeoxy analogs of the trisaccharide alpha-D-Glcp-(1 -> 3)-alpha-D-Manp-(1 -> 2)-alpha-D-ManpOMe have been developed. For the introduction of the 2'- and 2"-deoxy motifs the most efficient way was to use a 1,2-di-bromo-mannosyl donor in silver triflate promoted couplings to construct the alpha-glycosidic linkage followed by reduction of the 2-bromo-function to a 2-deoxy motif at the di- or trisaccharide level. In contrast, the 4"- and 6-deoxy functions were introduced already at the monosaccharide stage. The most challenging part of the syntheses was the stereoselective formation of the non-reducing end cis-alpha-D-glucosidic linkages. The established alpha-directing effect of a 3-O-acetyl group in glucosyl donors was explored but the magnitude of the effect was variable and dependent on donor/acceptor structure and nature of promoter and an optimization had to be made for each individual glycosylation. PMID- 26257377 TI - An efficient synthesis of novel bis-triazole glycoconjugates via a three component condensation as a key reaction. AB - Novel bis-triazole glycoconjugates were designed and prepared successfully via 5 steps from propargyl per-O-acetyl-beta-d-glucoside or xyloside (total yield of 48 53%), after utilizing a three-component condensation of propargyl per-O-acetyl beta-d-glycoside, formaldehyde, and sodium azide as a key step to synthesize 2 hydroxymethyl-2H-1,2,3-triazole glycoconjugates. The developed bis-triazole glycoconjugates would be crucial in antivirus pharmacology and chemical biology. PMID- 26257378 TI - Docking polysaccharide to proteins that have a Tryptophan box in the binding pocket. AB - Protein-carbohydrate interactions (PCIs) involve a variety of essential biological processes such as cell recognition and migration, metabolism processes and immunological reactions, which are important for securing functions of living organisms. Due to the polysaccharide structural diversity and dynamics flexibility, PCIs can be very difficult for experimental measurement and computer prediction. Here we report a simple method for docking polysaccharide to proteins whose binding pockets have a Tryptophan box. The method samples polysaccharide conformations using constraint conditions imposed by the box, evaluate the conformation energies based on a knowledge-based potential function, and finds the best docking structures using the conventional Monte Carlo simulated annealing technique. We applied the method to dock polysaccharides with 2 to 4 monomers to three carbohydrate-binding proteins, whose pockets have clear aromatic residue-defined binding channels. The predictions found correct carbohydrate binding conformations with atomic RMSD of 1.1-1.6 A from X-ray crystal structures. The calculation can be performed in ordinary PC and only cost a couple of minutes for a single docking. Our method, when combined with other docking programs, provides a reliable start conformation for further accurate simulation of PCIs. PMID- 26257379 TI - Osteoinductive silk fibroin/titanium dioxide/hydroxyapatite hybrid scaffold for bone tissue engineering. AB - The present study demonstrated the fabrication that incorporation of titanium isopropoxide (TiO2) and hydroxyapatite (HA) nanoparticles into the silk fibroin (SF) scaffolds. In this process, we prepared TiO2 nanoparticles using sol-gel synthesis and the porous structure was developed by salt-leaching process. Homogeneous distribution of TiO2 and HA nanoparticles were confirmed by images of VP-FE-SEM and those equipped with energy dispersive X-ray spectrometer. Structural characteristics of the porous SF/TiO2/HA hybrid scaffold were also determined using FTIR analysis and X-ray diffractometer. In this study, the porous SF/TiO2/HA hybrid scaffold showed similar porosity, enhanced mechanical property, but decreased water binding abilities, compared with the porous SF scaffold. For evaluation of the osteogenic differentiation of rat bone marrow mesenchymal stem cells, alkaline phosphatase activity and osteogenic gene expression were employed. Our results revealed that the porous SF/TiO2/HA hybrid scaffold had improved osteoinductivity compared with the porous SF scaffold. These results suggest that the osteogenic property as well as mechanical property of the porous SF/TiO2/HA hybrid scaffold could be better than the porous SF scaffold. Therefore, the porous SF/TiO2/HA hybrid scaffold may be a good promising biomaterial for bone tissue engineering application. PMID- 26257380 TI - In vitro release and biological activities of Carum copticum essential oil (CEO) loaded chitosan nanoparticles. AB - In recent years, the unparalleled and functional properties of essential oils have been extensively reported, but the sensitivity of essential oils to environmental factors and their poor aqueous solubility have limited their applications in industries. Hence, we encapsulated CEO in chitosan nanoparticles by an emulsion-ionic gelation with pantasodium tripolyphosphate (TPP) and sodium hexametaphosphte (HMP), separately, as crosslinkers. The nanoparticles were analyzed by Fourier transform infrared spectroscopy (FT-IR), Ultraviolet-visible spectroscopy (UV-vis), differential scanning calorimetry (DSC), scanning electron microscope (SEM) and dynamic light scattering (DLS). The encapsulation efficiency (EE) and loading capacity (LC) of CEO in chitosan nanoparticles increased with the increase of initial CEO amount. The nanoparticles displayed an average size of 30-80nm with a spherical shape and regular distribution. In vitro release profiles exhibited an initial burst release and followed by a sustained CEO release at different pH conditions. The amount of CEO release from chitosan nanoparticles was higher in acidic pH to basic or neutral pH, respectively. The biological properties of CEO, before and after the encapsulation process were evaluated by 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and agar disk diffusion method, respectively. The results indicated the encapsulation of CEO in chitosan nanoparticles could be protected the quality. PMID- 26257381 TI - Production and characterization of poly-3-hydroxybutyrate from Bacillus cereus PS 10. AB - Usage of renewable raw materials for production of fully degradable bioplastics (bacterial poly-3-hydroxybutyrate, PHB) has gained immense research impetus considering recalcitrant nature of petroleum based plastics, dwindling fossil fuel feed stocks, and associated green house gas emissions. However, high production cost of PHB is the major bottleneck for its wide range industrial applications. In current study, Bacillus cereus PS 10, a recent isolate, efficiently utilized molasses, an abundantly available by-product from sugar industries as sole carbon source for growth and PHB production. Most influential bioprocess variables i.e. molasses, pH and NH4Cl were identified based on Plackett-Burman-designed experiments. Design of experiment approach (response surface methodology) was further employed for optimization of these bioprocess variables, and an enhanced PHB yield (57.5%) was obtained. PHB produced by Bacillus cereus PS 10 was investigated using various physico-chemical approaches viz. thermogravimetric analysis, proton and carbon NMR ((1)H and (13)C) spectroscopy, melting point, elemental analysis and polarimetry for its detail characterization, and assessment for industrial application potential. PMID- 26257382 TI - CgIL17-5, an ancient inflammatory cytokine in Crassostrea gigas exhibiting the heterogeneity functions compared with vertebrate interleukin17 molecules. AB - Interleukin 17 (IL17) is a proinflammatory cytokine that plays an important role in immune response. Recently, five novel IL17 homologs have been identified by screening and analyzing the genome of pacific oyster Crassostrea gigas. In the present study, the functions of CgIL17-5 were investigated by examining the distribution of its mRNA and protein, ligands binding and modulation in immune response. The mRNA expression levels of CgIL17-5 in hemocytes of oysters post twice challenges of Vibrio splendidus were all significantly up-regulated (P < 0.01), while the secondary pathogen infection attenuated the expression level of CgIL17-5 mRNA compared with the primary challenge. CgIL17-5 was found to be located on oyster hemocyte membranes through fluorescence confocal assay. The luciferase reporter assays showed that CgIL17-5 could activate the transfactors NF-kappaB, CREB and ATF-1, and involve in their signal pathways in HEK293T cells. Meanwhile, CgIL17-5 could augment the IL6 synthesis in HuVEC cells, playing the similar roles as human IL17 in inflammatory response. Additionally, the recombinant CgIL17-5 (rCgIL17-5) could directly bind peptidoglycan (PGN), lipopolysaccharide (LPS), poly (I:C) and beta-1,3-glucan, with the highest affinity to PGN, and significantly inhibit the growth of Micrococcus luteus and Escherichia coli. All the results collectively suggested that CgIL17-5, as an ancient inflammatory cytokine, could not only activate signal transduction for the release of other cytokines, but also mediate the clearance of extracellular bacteria in oysters. PMID- 26257383 TI - Yellow nail syndrome: a case report and review of treatment options. AB - BACKGROUND AND AIMS: Yellow nail syndrome is a rare disorder involving characteristic nail changes, lymphedema and chronic respiratory symptoms. Currently there is no definitive treatment and there have been no prospective randomised controlled trials evaluating the available options. In order to strengthen the literature on this topic, we present the case of a 67-year-old man with YNS and a detailed review of current treatment options. METHODS: We included 40 articles for the final review according to their relevance with the subject. RESULTS: Data for use of the commonly chosen therapies for YNS remains inconclusive, with small studies and case reports showing mixed results of efficacy. CONCLUSION: Although the date indicates that it is reasonable to recommend a trial of conservative therapy including vitamin E, antibiotics and compression stockings before pursuing more aggressive or invasive modalities, larger scale studies are required to determine the true efficacy of all treatment options. PMID- 26257384 TI - Adenosine monophosphate is not superior to histamine for bronchial provocation test for assessment of asthma control and symptoms. AB - BACKGROUND: Adenosine monophosphate (AMP) may reflect airway inflammation and hyperresponsiveness, but relationship between AMP and histamine (His, a conventional stimulus) bronchial provocation test (BPT) in asthma is not fully elucidated. OBJECTIVES: To compare both BPTs and determine their utility in reflecting changes of asthmatic symptoms. METHODS: BPTs were performed in a cross over fashion, at 2-4 day intervals. Cumulative doses eliciting 20% FEV1 fall (PD20 FEV1 ), diagnostic performance and adverse events (AEs) were compared. Patients with PD20 FEV1 lower than geometric mean were defined as responders, otherwise poor responders. Patients with uncontrolled and partly controlled asthma, who maintained their original inhaled corticosteroids therapy, underwent reassessment of airway responsiveness and asthmatic symptoms 3 and 6 months after. RESULTS: Nineteen uncontrolled, 22 partly controlled and 19 controlled asthmatic patients and 24 healthy subjects were recruited. Lower PD20 FEV1 geometric means were associated with poorer asthma control in His-BPT (0.424 MUmol vs 1.684 MUmol vs 3.757 MUmol), but not AMP-BPT (11.810 MUmol vs 7.781 MUmol vs 10.220 MUmol). Both BPTs yielded similar overall diagnostic performance in asthma (area under curve: 0.842 in AMP-BPT vs 0.850 in His-BPT). AEs, including wheezing and tachypnea, were similar and mild. Ten patients with uncontrolled and 10 partly controlled asthma were followed-up. At months 3 and 6, we documented an increase in PD20 FEV1 -AMP and PD20 FEV1 -His, which did not correlate with reduction asthmatic symptom scores. This overall applied in responders and poor responders of AMP-BPT and His-BPT. CONCLUSION: Despite higher screening capacity of well-controlled asthma, AMP-BPT confers similar diagnostic performance and safety with His-BPT. AMP-BPT might not preferentially reflect changes asthmatic symptoms. PMID- 26257385 TI - AMPLISAS: a web server for multilocus genotyping using next-generation amplicon sequencing data. AB - Next-generation sequencing (NGS) technologies are revolutionizing the fields of biology and medicine as powerful tools for amplicon sequencing (AS). Using combinations of primers and barcodes, it is possible to sequence targeted genomic regions with deep coverage for hundreds, even thousands, of individuals in a single experiment. This is extremely valuable for the genotyping of gene families in which locus-specific primers are often difficult to design, such as the major histocompatibility complex (MHC). The utility of AS is, however, limited by the high intrinsic sequencing error rates of NGS technologies and other sources of error such as polymerase amplification or chimera formation. Correcting these errors requires extensive bioinformatic post-processing of NGS data. Amplicon Sequence Assignment (AMPLISAS) is a tool that performs analysis of AS results in a simple and efficient way, while offering customization options for advanced users. AMPLISAS is designed as a three-step pipeline consisting of (i) read demultiplexing, (ii) unique sequence clustering and (iii) erroneous sequence filtering. Allele sequences and frequencies are retrieved in excel spreadsheet format, making them easy to interpret. AMPLISAS performance has been successfully benchmarked against previously published genotyped MHC data sets obtained with various NGS technologies. PMID- 26257386 TI - Disrupted topological organization of resting-state functional brain network in subcortical vascular mild cognitive impairment. AB - AIMS: Neuroimaging studies have demonstrated both structural and functional abnormalities in widespread brain regions in patients with subcortical vascular mild cognitive impairment (svMCI). However, whether and how these changes alter functional brain network organization remains largely unknown. METHODS: We recruited 21 patients with svMCI and 26 healthy control (HC) subjects who underwent resting-state functional magnetic resonance imaging scans. Graph theory based network analyses were used to investigate alterations in the topological organization of functional brain networks. RESULTS: Compared with the HC individuals, the patients with svMCI showed disrupted global network topology with significantly increased path length and modularity. Modular structure was also impaired in the svMCI patients with a notable rearrangement of the executive control module, where the parietal regions were split out and grouped as a separate module. The svMCI patients also revealed deficits in the intra- and/or intermodule connectivity of several brain regions. Specifically, the within module degree was decreased in the middle cingulate gyrus while it was increased in the left anterior insula, medial prefrontal cortex and cuneus. Additionally, increased intermodule connectivity was observed in the inferior and superior parietal gyrus, which was associated with worse cognitive performance in the svMCI patients. CONCLUSION: Together, our results indicate that svMCI patients exhibit dysregulation of the topological organization of functional brain networks, which has important implications for understanding the pathophysiological mechanism of svMCI. PMID- 26257387 TI - Exposure to Methylmercury Does Not Change the Sexual Preference of C57BL Male Mice. PMID- 26257388 TI - Gibbs ringing in diffusion MRI. AB - PURPOSE: To study and reduce the effect of Gibbs ringing artifact on computed diffusion parameters. METHODS: We reduce the ringing by extrapolating the k-space of each diffusion weighted image beyond the measured part by selecting an adequate regularization term. We evaluate several regularization terms and tune the regularization parameter to find the best compromise between anatomical accuracy of the reconstructed image and suppression of the Gibbs artifact. RESULTS: We demonstrate empirically and analytically that the Gibbs artifact, which is typically observed near sharp edges in magnetic resonance images, has a significant impact on the quantification of diffusion model parameters, even for infinitesimal diffusion weighting. We find the second order total generalized variation to be a good choice for the penalty term to regularize the extrapolation of the k-space, as it provides a parsimonious representation of images, a practically full suppression of Gibbs ringing, and the absence of staircasing artifacts typical for total variation methods. CONCLUSIONS: Regularized extrapolation of the k-space data significantly reduces truncation artifacts without compromising spatial resolution in comparison to the default option of window filtering. In particular, accuracy of estimating diffusion tensor imaging and diffusion kurtosis imaging parameters improves so much that unconstrained fits become possible. Magn Reson Med 76:301-314, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26257389 TI - Detection of a novel stem cell probably involved in normal turnover of the lung airway epithelium. AB - Regeneration of the lung airway epithelium after injury has been extensively studied. In contrast, analysis of its turnover in healthy adulthood has received little attention. In the classical view, this epithelium is maintained in the steady-state by the infrequent proliferation of basal or Clara cells. The intermediate filament protein nestin was initially identified as a marker for neural stem cells, but its expression has also been detected in other stem cells. Lungs from CD1 mice at the age of 2, 6, 12, 18 or 24 months were fixed in neutral buffered formalin and paraffin-embedded. Nestin expression was examined by an immunohistochemical peroxidase-based method. Nestin-positive cells were detected in perivascular areas and in connective tissue that were in close proximity of the airway epithelium. Also, nestin-positive cells were found among the cells lining the airway epithelium. These findings suggest that nestin-positive stem cells circulate in the bloodstream, transmigrate through blood vessels and localize in the lung airway epithelium to participate in its turnover. We previously reported the existence of similar cells able to differentiate into lung chondrocytes. Thus, the stem cell reported here might be a bone marrow derived mesenchymal stem cell (BMDMSC) able to generate several types of lung tissues. In conclusion, our findings indicate that there exist a BMDMSC in healthy adulthood that participates in the turnover of the lung airway epithelium. These findings may improve our knowledge about the lung stem cell biology and also provide novel approaches to therapy for devastating pulmonary diseases. PMID- 26257390 TI - Intracellular pH modulates quinary structure. AB - NMR spectroscopy can provide information about proteins in living cells. pH is an important characteristic of the intracellular environment because it modulates key protein properties such as net charge and stability. Here, we show that pH modulates quinary interactions, the weak, ubiquitous interactions between proteins and other cellular macromolecules. We use the K10H variant of the B domain of protein G (GB1, 6.2 kDa) as a pH reporter in Escherichia coli cells. By controlling the intracellular pH, we show that quinary interactions influence the quality of in-cell (15) N-(1) H HSQC NMR spectra. At low pH, the quality is degraded because the increase in attractive interactions between E. coli proteins and GB1 slows GB1 tumbling and broadens its crosspeaks. The results demonstrate the importance of quinary interactions for furthering our understanding of protein chemistry in living cells. PMID- 26257391 TI - Incremental Utility of Real Time Three-Dimensional Transthoracic Echocardiography for the Assessment of Left Ventricular Free Wall Rupture Location, Orifice Geometry, and Complex Intracardiac Flow. PMID- 26257392 TI - Salvianolic acid B-induced microRNA-152 inhibits liver fibrosis by attenuating DNMT1-mediated Patched1 methylation. AB - Epithelial-mesenchymal transition (EMT) was reported to be involved in the activation of hepatic stellate cells (HSCs), contributing to the development of liver fibrosis. Epithelial-mesenchymal transition can be promoted by the Hedgehog (Hh) pathway. Patched1 (PTCH1), a negative regulatory factor of the Hh signalling pathway, was down-regulated during liver fibrosis and associated with its hypermethylation status. MicroRNAs (miRNAs) are reported to play a critical role in the control of various HSCs functions. However, miRNA-mediated epigenetic regulations in EMT during liver fibrosis are seldom studied. In this study, Salvianolic acid B (Sal B) suppressed the activation of HSCs in CCl4 -treated mice and mouse primary HSCs, leading to inhibition of cell proliferation, type I collagen and alpha-smooth muscle actin. We demonstrated that the antifibrotic effects caused by Sal B were, at least in part, via inhibition of EMT and the Hh pathway. In particular, up-regulation of PTCH1 was associated with decreased DNA methylation level after Sal B treatment. Accordingly, DNA methyltransferase 1 (DNMT1) was attenuated by Sal B in vivo and in vitro. The knockdown of DNMT1 in Sal B-treated HSCs enhanced PTCH1 expression and its demethylation level. Interestingly, increased miR-152 in Sal B-treated cells was responsible for the hypomethylation of PTCH1 by Sal B. As confirmed by the luciferase activity assay, DNMT1 was a direct target of miR-152. Further studies showed that the miR-152 inhibitor reversed Sal B-mediated PTCH1 up-regulation and DNMT1 down-regulation. Collectively, miR-152 induced by Sal B, contributed to DNMT1 down-regulation and epigenetically regulated PTCH1, resulting in the inhibition of EMT in liver fibrosis. PMID- 26257394 TI - Left Ventricular Side Obstructive Pannus Formation after Rheumatic Mitral Valve Replacement with Preservation of the Subvalvular Apparatus. PMID- 26257393 TI - Large-scale identification of membrane proteins with properties favorable for crystallization. AB - Membrane protein crystallography is notoriously difficult due to challenges in protein expression and issues of degradation and structural stability. We have developed a novel method for large-scale screening of native sources for integral membrane proteins that have intrinsic biochemical properties favorable for crystallization. Highly expressed membrane proteins that are thermally stable and nonaggregating in detergent solutions were identified by mass spectrometry from Escherichia coli, Saccharomyces cerevisiae, and Sus scrofa cerebrum. Many of the membrane proteins identified had been crystallized previously, supporting the promise of the approach. Most identified proteins have known functions and include high-value targets such as transporters and ATPases. To validate the method, we recombinantly expressed and purified the yeast protein, Yop1, which is responsible for endoplasmic reticulum curvature. We demonstrate that Yop1 can be purified with the detergent dodecylmaltoside without aggregating. PMID- 26257395 TI - Angiotensin type 1a receptors on corticotropin-releasing factor neurons contribute to the expression of conditioned fear. AB - Although generally associated with cardiovascular regulation, angiotensin II receptor type 1a (AT1a R) blockade in mouse models and humans has also been associated with enhanced fear extinction and decreased post-traumatic stress disorder (PTSD) symptom severity, respectively. The mechanisms mediating these effects remain unknown, but may involve alterations in the activities of corticotropin-releasing factor (CRF)-expressing cells, which are known to be involved in fear regulation. To test the hypothesis that AT1a R signaling in CRFergic neurons is involved in conditioned fear expression, we generated and characterized a conditional knockout mouse strain with a deletion of the AT1a R gene from its CRF-releasing cells (CRF-AT1a R((-/-)) ). These mice exhibit normal baseline heart rate, blood pressure, anxiety and locomotion, and freeze at normal levels during acquisition of auditory fear conditioning. However, CRF-AT1a R((-/ )) mice exhibit less freezing than wild-type mice during tests of conditioned fear expression-an effect that may be caused by a decrease in the consolidation of fear memory. These results suggest that central AT1a R activity in CRF expressing cells plays a role in the expression of conditioned fear, and identify CRFergic cells as a population on which AT1 R antagonists may act to modulate fear extinction. PMID- 26257397 TI - Saline Contrast Echocardiography in the Era of Multimodality Imaging--Importance of "Bubbling It Right". AB - Saline contrast echocardiography is an established imaging modality. Logical interpretation of a carefully performed study is vital to realize its diagnostic potential. In this review, we discuss utility of saline contrast echocardiography in evaluation of various pathologies within and outside the heart other than a patent foramen ovale. PMID- 26257396 TI - Differential backbone dynamics of companion helices in the extended helical coiled-coil domain of a bacterial chemoreceptor. AB - Cytoplasmic domains of transmembrane bacterial chemoreceptors are largely extended four-helix coiled coils. Previous observations suggested the domain was structurally dynamic. We probed directly backbone dynamics of this domain of the transmembrane chemoreceptor Tar from Escherichia coli using site-directed spin labeling and electron paramagnetic resonance (EPR) spectroscopy. Spin labels were positioned on solvent-exposed helical faces because EPR spectra for such positions reflect primarily polypeptide backbone movements. We acquired spectra for spin-labeled, intact receptor homodimers solubilized in detergent or inserted into native E. coli lipid bilayers in Nanodiscs, characterizing 16 positions distributed throughout the cytoplasmic domain and on both helices of its helical hairpins, one amino terminal to the membrane-distal tight turn (N-helix), and the other carboxyl terminal (C-helix). Detergent solubilization increased backbone dynamics for much of the domain, suggesting that loss of receptor activities upon solubilization reflects wide-spread destabilization. For receptors in either condition, we observed an unanticipated difference between the N- and C-helices. For bilayer-inserted receptors, EPR spectra from sites in the membrane-distal protein-interaction region and throughout the C-helix were typical of well structured helices. In contrast, for approximately two-thirds of the N-helix, from its origin as the AS-2 helix of the membrane-proximal HAMP domain to the beginning of the membrane-distal protein-interaction region, spectra had a significantly mobile component, estimated by spectral deconvolution to average approximately 15%. Differential helical dynamics suggests a four-helix bundle organization with a pair of core scaffold helices and two more dynamic partner helices. This newly observed feature of chemoreceptor structure could be involved in receptor function. PMID- 26257398 TI - The antimicrobial effect of chlorhexidine varnish on mutans streptococci in patients with fixed orthodontic appliances: a systematic review of clinical efficacy. AB - OBJECTIVE: To conduct a systematic review aimed to determine the antimicrobial efficacy of chlorhexidine varnishes (CHX-V) on mutans streptococci (MS) in patients during orthodontic treatment with fixed appliances. MATERIALS AND METHODS: A systematic computerized database search was conducted using Ovid MEDLINE, Scopus and EMBASE up to September 2014. A Google search was also conducted to further identify articles that met the eligibility criteria. Clinical trials which used CHX-V alone as the intervention to investigate the antimicrobial effect of the varnish in subjects undergoing orthodontic treatment were included. Outcome measures included MS level reduction and/or decreased caries incidence from baseline data. RESULTS: Nineteen articles were identified for full-text reading; eleven articles met the criteria for inclusion in this review. Type and concentration of CHX-V, bacterial sampling method, application frequency, sampling schedule, risk of bias and study outcomes are presented. CONCLUSION: A limited number of studies with low risk of bias were available to address the antimicrobial efficacy of CHX-V on MS in patients during orthodontic treatment with fixed appliances. Therefore, while the majority of studies found CHX-V to be an effective antimicrobial against MS at an interval of 3-4 weeks, the strength of the recommendation is weak. Longitudinal studies are needed to determine whether this antimicrobial effect will contribute to clinically significant caries reduction in patients undergoing orthodontic treatment with fixed appliances. PMID- 26257400 TI - The effect of antimicrobial agents on bond strength of orthodontic adhesives: a meta-analysis of in vitro studies. AB - Antimicrobial orthodontic adhesives aim to reduce white spot lesions' incidence in orthodontic patients, but they should not jeopardizing its properties. Systematic review and meta-analysis were performed to answer the question whether the association of antimicrobial agents with orthodontic adhesives compromises its mechanical properties and whether there is a superior antimicrobial agent. PubMed and Scopus databases. In vitro studies comparing shear bond strength of conventional photo-activated orthodontic adhesives to antimicrobial photo activated orthodontic adhesives were considered eligible. Search terms included the following: orthodontics, orthodontic, antimicrobial, antibacterial, bactericidal, adhesive, resin, resin composite, bonding agent, bonding system, and bond strength. The searches yielded 494 citations, which turned into 467 after duplicates were discarded. Titles and abstracts were read and 13 publications were selected for full-text reading. Twelve studies were included in the meta-analysis. The global analysis showed no statistically significant difference between control and experimental groups. In the subgroup analysis, only the chlorhexidine subgroup showed a statistically significant difference, where the control groups had higher bond strength than the experimental groups. Many studies on in vitro orthodontic bond strength fail to report test conditions that could affect their outcomes. The pooled in vitro data suggest that adding an antimicrobial agent to an orthodontic adhesive system does not influence bond strength to enamel. It is not possible to state which antimicrobial agent is better to be associated. PMID- 26257399 TI - The structure of the Caenorhabditis elegans manganese superoxide dismutase MnSOD 3-azide complex. AB - C. elegans MnSOD-3 has been implicated in the longevity pathway and its mechanism of catalysis is relevant to the aging process and carcinogenesis. The structures of MnSOD-3 provide unique crystallographic evidence of a dynamic region of the tetrameric interface (residues 41-54). We have determined the structure of the MnSOD-3-azide complex to 1.77-A resolution. Analysis of this complex shows that the substrate analog, azide, binds end-on to the manganese center as a sixth ligand and that it ligates directly to a third and new solvent molecule also positioned within interacting distance to the His30 and Tyr34 residues of the substrate access funnel. This is the first structure of a eukaryotic MnSOD-azide complex that demonstrates the extended, uninterrupted hydrogen-bonded network that forms a proton relay incorporating three outer sphere solvent molecules, the substrate analog, the gateway residues, Gln142, and the solvent ligand. This configuration supports the formation and release of the hydrogen peroxide product in agreement with the 5-6-5 catalytic mechanism for MnSOD. The high product dissociation constant k4 of MnSOD-3 reflects low product inhibition making this enzyme efficient even at high levels of superoxide. PMID- 26257401 TI - Use of caprylic acid to control pathogens (Escherichia coli O157:H7 and Salmonella enterica serovar Typhimurium) in apple juice at mild heat temperature. AB - AIMS: The aim of this study was to examine the effects of caprylic acid (CA) on pathogens in apple juice having intrinsic organic acids, and to determine any synergistic effects. METHODS AND RESULTS: Bactericidal effects of CA were examined against Escherichia coli O157:H7 and Salmonella Typhimurium present in apple juice at mild heating temperatures. Apple juice containing each of the pathogens was treated with CA (0.1, 0.2, 0.4, 0.6 or 0.8 mmol l(-1)) at 50 or 55 degrees C. Treatment with 0.8 mmol l(-1) (0.013%) CA at 50 degrees C for 5 min or with 0.6 mmol l(-1) (0.010%) CA at 55 degrees C for 5 min resulted in the complete eradication of E. coli O157:H7 (initial population: 7.25-7.34 log CFU ml(-1)). Salmonella Typhimurium were more sensitive than E. coli O157:H7: all bacteria (7.81-7.55 log CFU ml(-1)) were eradicated by treatment with 0.2 mmol l( 1) (0.0032%) CA at 55 degrees C for 5 min or with 0.6 mmol l(-1) CA at 50 degrees C for 5 min. By contrast, when pH-adjusted apple juice (pH 7.0) was treated with 0.8 mmol l(-1) CA, there was no significant difference in bactericidal effects between CA-treated samples and controls (heat treatment alone or heat + 0.1% ethanol treatment). This result suggested that acidic pH in the apple juice boost the antibacterial effects of CA. CA treatment did not affect (P > 0.05) the pH, colour or degrees Brix of the apple juice. CONCLUSION: This study highlights the utility of CA as a natural antibacterial agent that can eliminate micro-organisms from apple juice at very low concentrations (<=0.013%) and temperatures (<=55 degrees C) within a short time (<=10 min). SIGNIFICANCE AND IMPACT OF THE STUDY: The results of our study may contribute to the development of an efficient method for improving the microbiological safety of apple juice. PMID- 26257402 TI - Effect of reward downshift on the behaviour and physiology of chickens. AB - When a reward is downgraded in quantity or quality from that which is expected, one of two possible outcomes can result. Acquisition responses may decline gradually, owing to a strong stimulus-response reinforcement history, and thus follow the Thorndikian law of effect. Alternatively, there may be an exaggerated reaction to a downgraded reward when it is initially altered, compared to the behaviour of individuals that have always been trained to receive the lower magnitude reward; this is known as successive negative contrast (SNC). While behavioural SNC effects have been commonly demonstrated in mammals, evidence that they occur in other taxa is more equivocal. Additionally, studies demonstrating immediate physiological reactions during reward downshifts are limited. We investigated the reaction of chickens, Gallus gallus domesticus, to a downshift in the quality of a food reward that they had been trained to expect in a runway apparatus. During a preshift phase, 16 chickens (control) were given food that was flavoured to make it less preferred, while the other 16 (contrast) were fed the same food but without flavouring. During trial 7, unflavoured food was substituted by flavoured food for contrast hens and all birds were fed the flavoured food during a postshift phase. In the contrast group, food consumption immediately decreased and heart rate increased when the reward was downshifted from unflavoured to flavoured food, but there was no evidence of SNC effects, which could stem from methodological or taxonomic differences from previous studies. The latency to reach the food appeared to follow the Thorndikian law of effect, gradually increasing following the downshift. We suggest that the disparity between the pattern shown by the latency results and other measures could relate to the time period in which measures were taken, as acquisition responses are more likely to follow the law of effect. PMID- 26257403 TI - Training for eye contact modulates gaze following in dogs. AB - Following human gaze in dogs and human infants can be considered a socially facilitated orientation response, which in object choice tasks is modulated by human-given ostensive cues. Despite their similarities to human infants, and extensive skills in reading human cues in foraging contexts, no evidence that dogs follow gaze into distant space has been found. We re-examined this question, and additionally whether dogs' propensity to follow gaze was affected by age and/or training to pay attention to humans. We tested a cross-sectional sample of 145 border collies aged 6 months to 14 years with different amounts of training over their lives. The dogs' gaze-following response in test and control conditions before and after training for initiating eye contact with the experimenter was compared with that of a second group of 13 border collies trained to touch a ball with their paw. Our results provide the first evidence that dogs can follow human gaze into distant space. Although we found no age effect on gaze following, the youngest and oldest age groups were more distractible, which resulted in a higher number of looks in the test and control conditions. Extensive lifelong formal training as well as short-term training for eye contact decreased dogs' tendency to follow gaze and increased their duration of gaze to the face. The reduction in gaze following after training for eye contact cannot be explained by fatigue or short-term habituation, as in the second group gaze following increased after a different training of the same length. Training for eye contact created a competing tendency to fixate the face, which prevented the dogs from following the directional cues. We conclude that following human gaze into distant space in dogs is modulated by training, which may explain why dogs perform poorly in comparison to other species in this task. PMID- 26257404 TI - Local and Systemic Therapies for Breast Cancer Patients: Reducing Short-term Symptoms with the Methods of Integrative Medicine. AB - With improved prognosis due to advances in the diagnosis and therapy of breast cancer, physicians and therapists now focus on aspects such as quality of life and the management of side effects from breast cancer treatment. Therapy- and disease-related side effects often reduce the patient's quality of life and can place a further burden on patients, with non-compliance or discontinuation of therapy a potential consequence. Study data have shown that therapy- and disease related side effects can be reduced using the methods of integrative medicine. Reported benefits include improving patients' wellbeing and quality of life, reducing stress, and improving patients' mood, sleeping patterns and capacity to cope with disease. Examining the impact of integrative medicine on the side effects of cancer treatment would be beyond the scope of this review. This article therefore looks at short-term side effects of cancer treatment which are usually temporary and occur during or after local and systemic therapy. The focus is on mind-body medicine, acupuncture and classic naturopathic treatments developed by Sebastian Kneipp as complementary therapies. The latter includes hydrotherapy, phytotherapy, nutritional therapy, exercise therapy and a balanced lifestyle. PMID- 26257405 TI - The Right Treatment for the Right Patient - Personalised Treatment of Breast Cancer. AB - The probability of healing breast cancer has been greatly improved in recent decades through the introduction and optimisation of multi-modal therapies and interdisciplinary treatments. Today, in addition to surgery or radiation, most patients receive a systemic treatment. To prevent excessive treatment, patients whose prognosis is so good that certain adjuvant therapies can be foregone or reduced must be identified. A lack of compliance with therapy, especially in the endocrine therapies stretching over years, is a further problem. As only treatments that are also carried out can improve chances of survival, efforts to improve compliance must be intensified. Studies show that lifestyle changes influence the efficiency of medication on the one hand, and on the other hand can also by themselves achieve a relevant improvement of the prognosis. Therefore, it is time not only to treat the tumour, but to also focus on the patient as a whole in therapeutic interventions. PMID- 26257406 TI - Patient-Reported Outcomes in Implant-Based Breast Reconstruction Alone or in Combination with a Titanium-Coated Polypropylene Mesh - A Detailed Analysis of the BREAST-Q and Overview of the Literature. AB - Background: Complication rates and surgical outcomes are well reported for implant-based breast reconstruction (IBBR) using supportive materials for the inferior pole of the breast. Patient-reported outcomes (PRO) are underrepresented. The aim of this study was to compare PRO in IBBR using implants alone or in combination with a synthetic mesh. Methods and Methods: PRO was measured in patients undergoing IBBR alone or in combination with a titanium covered polypropylene mesh (TiLOOP(r) Bra). In this non-randomized observational trial PRO was retrospectively assessed using the validated self-reporting BREAST Q. The raw responses of all questions applied in each domain and transformed BREAST-Q data using the Q-Score are presented. Results: Of 90 eligible women, 42 received IBBR alone and 48 received IBBR in combination with mesh. No differences in complication rates were observed. The return rate was 67.7 % and was comparable between the groups (p = 0.117). PRO revealed no differences regarding satisfaction with breast shape (p = 0.079), outcome (p = 0.604), nipple sensitivity (p = 0.502), preoperative information (p = 0.195), office staff (p = 0.462), psychosocial well-being (p = 0.370), sexual well-being (p = 0.508) and physical well-being (p = 0.654). Significant differences were noted regarding satisfaction with the surgeon (p = 0.013) and medical staff (p = 0.035) as well as the response behavior of certain questions of the sub-domains, thus helping to further stratify PRO with regards to aesthetic outcome. However, no differences were observed in the main BREAST-Q results. Conclusion: Use of the TiLOOP(r) Bra in IBBR results in comparable BREAST-Q scores compared with IBBR alone. Evaluating the BREAST-Q sub-domains helps to stratify PRO more profoundly and assists in interpreting the overall results and specific research questions. PMID- 26257407 TI - Psychosocial Information Requirements for Multimorbid Breast Cancer Patients in Breast Centres in North Rhine Westphalia. AB - Introduction: The importance of breast cancer patients (BPs) being supplied with sufficient information is well known. This study investigated the unfulfilled psychosocial information requirements of multimorbid BPs. Methods: This study records the unfulfilled psychosocial information requirements of 4166 patients, who were treated at one of the fifty breast centres in North Rhine Westphalia. The Cologne patient questionnaire for breast cancer 2.0 included in the postal survey following hospital stays records the information requirements using an adapted version of the "Cancer patient information needs" scale. Through a univariate analysis using the chi2 test, it was investigated whether multimorbid BPs had significantly different psychosocial information requirements than BPs without further concomitant illnesses. Results: In general, it transpired that BPs had relatively low unfulfilled information requirements regarding work (20.7 %), everyday life (26.8 %), illness (27.4 %) and treatment (35.7 %), though such requirements were higher when it came to health-related behaviour (54.2 %). Multimorbid BPs had significantly lower unfulfilled information requirements regarding work and significantly larger ones regarding treatment in comparison to BPs without concomitant illnesses. Renal diseases and concomitant mental illnesses were associated with particularly high information requirements (p < 0.05). Conclusion: The results of our study should clarify the complexity and heterogeneity of information requirements of breast cancer patients in oncological care and should help to design the supply of information to be more patient-oriented. PMID- 26257408 TI - Prognostic Factors for Local, Loco-regional and Systemic Recurrence in Early stage Breast Cancer. AB - Aim: The risk of recurrence in breast cancer depends on factors such as treatment but also on the intrinsic subtype. We analyzed the risk factors for local, loco regional and systemic recurrence, evaluated the differences and analyzed the risk of recurrence for different molecular subtypes. Material and Methods: A total of 3054 breast cancer patients who underwent surgery followed by adjuvant treatment at HSK hospital or Essen Mitte Hospital between 1998 and 2011 were analyzed. Based on immunohistochemical parameters, cancers were divided into the following subgroups: luminal A, luminal B (HER2-), luminal B (HER2+), HER2+ and TNBC (triple negative breast cancer). Results: 67 % of tumors were classified as luminal A, 13 % as luminal B (HER2-), 6 % as luminal B (HER2+), 3 % as HER2+ and 11 % as TNBC. After a median follow-up time of 6.6 years there were 100 local (3.3 %), 32 loco-regional (1 %) and 248 distant recurrences (8 %). Five-year recurrence-free survival for the overall patient collective was 92 %. On multivariate analysis, positive nodal status, TNBC subtype and absence of radiation therapy were found to be independent risk factors for all forms of recurrence. Age < 50 years, tumor size, luminal B (HER2-) subtype and breast conserving therapy were additional risk factors for local recurrence. Compared to the luminal A subtype, the risk of systemic recurrence was higher for all other subtypes; additional risk factors for systemic recurrence were lymphatic invasion, absence of systemic therapy and mastectomy. Conclusion: Overall, the risk of local and loco-regional recurrence was low. In addition to nodal status, subgroup classification was found to be an important factor affecting the risk of recurrence. PMID- 26257409 TI - Detection of Subpubic Tumor Causing Bladder Outlet Obstruction by 3D Perineal Ultrasound. AB - This case report shows that 3D perineal ultrasound can be superior to clinical examination and routine 2D perineal ultrasound in the detection of an unusual subpubic tumor. A 73-year-old female patient was referred to our urogynecological outpatient unit complaining of over-active bladder symptoms and voiding dysfunction for 3 years. Gynecological examination found no signs of pelvic organ prolapse or abnormality in the vaginal cavity. Routine 2D perineal ultrasound showed substantial residual urine (ca. 300 ml on catheter) and limited bladder neck mobility, but no signs of pelvic organ prolapse. Use of standardized 3D perineal ultrasound revealed a 24 * 26 * 32 mm spherical, hypoechoic tumor below the pubic symphysis between the distal urethra and the pubic bones. This structure was mistaken for the pubic symphysis in the midline on 2D ultrasound performed earlier. At surgery, the tumor was completely excised through a vaginal incision between the urethra and the pubic symphysis. After an uneventful postoperative recovery the patient developed de-novo stress urinary incontinence, which was corrected successfully by the insertion of a retropubic tension-free suburethral sling after an interval of 8 weeks. After a further follow-up of 8 weeks the patient reported well-being, urinary continence and no voiding dysfunction; no abnormalities were found on examination. In conclusion, 3D perineal ultrasound is a useful additional tool for the diagnostic workup of bladder outlet obstruction. PMID- 26257410 TI - Scientific misconduct and unethical practices in anaesthesiology: Stumbling blocks to quality research and publications. PMID- 26257411 TI - Scientific misconducts and authorship conflicts: Indian perspective. AB - This article is a narrative review about how appropriate authorship can be achieved, a brief mention about various scientific misconducts, the reason and consequences of such misconducts and finally, the policies to be adopted by the aspiring authors to avert these problems. The literature search was performed in the Google and PubMed using 'scientific misconduct', 'honorary/ghost authorship', 'publish-or-perish', 'plagiarism' and other related key words and phrases. More than 300 free full-text articles published from 1990 to 2015 were retrieved and studied. Many consensus views have been presented regarding what constitutes authorship, the authorship order and different scientific misconducts. The conflicts about authorship issues related to publication of dissertation, the area of the grey zone have been discussed. Suggestions from different authorities about improving the existing inappropriate authorship issues have been included. PMID- 26257412 TI - Comparative study of EpisureTM AutoDetectTM syringe versus glass syringe for identification of epidural space in lower thoracic epidural. AB - BACKGROUND AND AIMS: EpisureTM AutoDetectTM syringe (EAS), a spring-loaded syringe, is a new loss-of-resistance syringe used to identify epidural space. It has an advantage of subjective and objective confirmation in identifying epidural space over glass syringe (GS) for beginners. We compared the performance of EAS with that of GS for identifying epidural space in lower thoracic epidurals. METHODS: A total of 120 American Society of Anesthesiolgists I-II patients aged 18-60 years requiring lower thoracic epidural analgesia for surgery were randomised into Group I (EAS): Epidural identified using EAS and Group II (GS) epidural identified with GS. Patient demographic data, depth to epidural space (cm), number of attempts, time to locate epidural space (s), inadvertent dural puncture and failed epidural analgesia were the parameters noted. RESULTS: There were no differences in patient demographics or depth to the epidural space between the two groups. There were five failed blocks in the GS group and none in the EAS group (P = 0.0287). Similarly, there were five inadvertent dural punctures in the GS group and none in the EAS group (P = 0.0287). When epidural was identified in fewer attempts, the time needed to identify epidural space was quicker with EAS (P = 0.0012). CONCLUSION: Using EAS allowed reliable and quick identification of the epidural space in lower thoracic epidural technique as compared to use of glass syringe. There was no incidence of inadvertent dural puncture or failed blocks with the EAS. PMID- 26257413 TI - Comparison of analgesic efficacy of flupirtine maleate and ibuprofen in gynaecological ambulatory surgeries: A randomized controlled trial. AB - BACKGROUND AND AIMS: Flupirtine maleate is a centrally acting, non-opioid analgesic with unique muscle relaxant properties as compared to common analgesics. The aim of this study was to compare post-operative analgesic efficacy of flupirtine maleate and ibuprofen in patients undergoing gynaecological ambulatory surgeries. METHODS: This prospective, randomised controlled study was conducted in 60 women of American Society of Anesthesiologists physical status I/II, 18-70 years of age and scheduled to undergo gynaecological ambulatory surgeries. The participants were randomised to receive either 100 mg oral flupirtine maleate (group flupirtine, n = 30) or 800 mg oral ibuprofen (group ibuprofen, n = 30), 1 h prior to surgery and then every 8 h for 48 h. Verbal Numerical Rating Scale (VNRS) on movement was assessed at 0, 2, 4, 6 and 8 h following surgery. Following discharge from hospital, the patients were interviewed telephonically at 12, 24 and 48 h post-operatively. VNRS was statistically analysed using Mann-Whitney test. RESULTS: VNRS on movement was statistically reduced at 2 h after surgery (P = 0.04) in group flupirtine as compared to group ibuprofen. The analgesic efficacy was similar in both the groups at 4, 6, 8, 12, 24 and 48 h after surgery. The satisfaction scores at 24 and 48 h post-operatively were superior in group flupirtine as compared to group ibuprofen (P < 0.001). CONCLUSION: Analgesic efficacy of flupirtine maleate was comparable with ibuprofen in patients in ambulatory gynaecological patients up to 48 h postoperatively with superior satisfaction scores. PMID- 26257414 TI - Effectiveness of single dose conivaptan for correction of hyponatraemia in post operative patients following major head and neck surgeries. AB - BACKGROUND AND AIMS: Conivaptan, a vasopressin receptor antagonist, is commonly used for the treatment of euvolaemic, hypervolaemic hyponatraemia. Usually, an intravenous (IV) bolus followed by infusion is administered for many days. We decided to assess the effectiveness of single dose conivaptan for correction of hyponatraemia in post-operative patients. METHODS: This was a prospective, randomised trial conducted in 40 symptomatic post-operative Intensive Care Unit (ICU) patients with a serum sodium level of <=130 mEq/L. Group A patients received IV conivaptan 20 mg over 30 min, whereas in group B infusion of 3% hypertonic saline was started as an infusion at the rate of 20-30 ml/h. Serum sodium levels were measured at 12, 24, 48 and 72 h and the daily fluid balance was measured for 3 days. The Chi-square test, Wilcoxon signed rank test and Mann Whitney tests were used as applicable. RESULTS: The serum sodium levels before initiating treatment were comparable between groups. However, subsequent sodium levels at 12, 24 and 48 h showed significantly high values in group A. Though at 72 h the mean sodium value was high in group A, it was not statistically significant. Group A showed a significantly high fluid loss on day 1, 2 and 3. The mean volume of hypertonic saline required in group B showed a steady decline from day 1 to 3 and only 13 patients required hypertonic saline on the 3(rd) day. CONCLUSION: Single dose conivaptan is effective in increasing serum sodium levels in post-operative ICU patients up to 72 h associated with a significant negative fluid balance. PMID- 26257415 TI - A prospective, randomised, clinical study to compare the use of McGrath((r)), Truview((r)) and Macintosh laryngoscopes for endotracheal intubation by novice and experienced Anaesthesiologists. AB - BACKGROUND AND AIMS: Video laryngoscopy has been recommended as an alternative during difficult conventional direct laryngoscopy using the Macintosh blade (MAC). However, successful visualisation of the larynx and tracheal intubation using some of the indirect laryngoscopes or video laryngoscopes (VL) requires hand-eye coordination. We conducted this study to determine whether non-channel VLs are easy to use for novices and whether there is any association between expertise with MAC and ease of tracheal intubation with VLs. METHODS: Anaesthesiologists participating in the study were divided into three groups: Group novice to intubation (NTI), Group novice to videoscope (NVL)- experienced with MAC, novice to VLs and Group expert (EXP) experienced in all. Group NTI, NVL received prior mannequin training. VLs- Truview((r)) and McGrath series 5 (MGR) were compared with MAC. One hundred and twenty six adult patients with normal airway were randomised to both, the intubating anaesthesiologist and laryngoscope. The time taken to intubate (TTI) and participants' rating of the ease of use was recorded on a scale of 1-10 (10-most difficult). RESULTS: In Group NTI, there was no difference in mean TTI with the three scopes (P = 0.938). In Group NVL, TTI was longer with the VLs than MAC (P < 0.001). In Group EXP, TTI with VL took 20 s more (P < 0.001). There was significant difference in participants' rating of ease of use of laryngoscope in Group NVL (P = 0.001) but not in the NTI (P = 0.205), EXP (P = 0.529) groups. A high failure was seen with MGR in Group NTI and NVL. CONCLUSION: In Group NTI, TTI and the ease of use were similar for all scopes. Expertise with standard direct laryngoscopy does not translate to expertise with VLs. Separate training and experience with VLs is required. PMID- 26257416 TI - Comparison of ketorolac and low-dose ketamine in preventing tourniquet-induced increase in arterial pressure. AB - BACKGROUND AND AIMS: Application of tourniquet during orthopaedic procedures causes pain and increase in blood pressure despite adequate anaesthesia and analgesia. In this study, we compared ketorolac with ketamine in patients undergoing elective lower limb surgery with tourniquet in order to discover if ketorolac was equally effective or better than ketamine in preventing tourniquet induced hypertension. METHODS: Approval was granted by the Institutional Ethics Review Committee and informed consent was obtained from all participants. A randomised double-blinded controlled trial with 38 patients each in the ketamine and ketorolac groups undergoing elective knee surgery for anterior cruciate ligament repair or reconstruction was conducted. Induction and maintenance of anaesthesia were standardised in all patients, and the minimum alveolar concentration of isoflurane was maintained at 1.2 throughout the study period. One group received ketamine in a dose of 0.25 mg/kg and the other group received 30 mg ketorolac 10 min before tourniquet inflation. Blood pressure was recorded before induction of anaesthesia (baseline) and at 0, 10, 20, 30, 40, 50, and 60 min after tourniquet inflation. RESULTS: The demographic and anaesthetic characteristics were similar in the two groups. At 0 and 10 min, tourniquet induced rise in blood pressure was not observed in both groups. From 20 min onward, both systolic and diastolic blood pressures were significantly higher in ketorolac group compared to ketamine group. CONCLUSION: We conclude that ketamine is superior to ketorolac in preventing tourniquet-induced increases in blood pressure. PMID- 26257417 TI - Hot charcoal vomitus in aluminum phosphide poisoning - A case report of internal thermal reaction in aluminum phosphide poisoning and review of literature. AB - Aluminium phosphide (ALP) poisoning is a commonly encountered poisoning in emergency departments in most developing countries. Many papers have revealed metabolic derangements in this poisoning and also examined contributing factors leading to death, but only few have reported physical damage. Some case reports have described a complication that has been frequently termed 'ignition'. The exact mechanism of this phenomenon has not been fully elucidated. An exothermic reaction during therapeutic administration of chemicals may contribute to this problem, but the incidence has occurred in the absence of treatment or drug administration. Here, we report a 34-year-old woman with ALP poisoning who presented with hot charcoal vomitus, a sign of internal thermal event, leading to the thermal burning of the patient's face and internal damage resulting in death. We reviewed all reported cases with similar complication to demonstrate varied characteristics of patients and to propose the possible mechanisms leading to this event. PMID- 26257418 TI - Oral midazolam is a safe and effective premedication in adult outpatients undergoing brachytherapy for cancer cervix under general anaesthesia: A prospective randomised, double blind placebo-controlled study. PMID- 26257419 TI - Anaesthetic management of a rare case of single ventricle heterotaxy syndrome for emergency caesarean section. PMID- 26257420 TI - Post-operative airway obstruction in Noonan syndrome: An unusual presentation. PMID- 26257421 TI - Use of ProSeal((r)) LMA and thoracic epidural in myasthenia patients for trans sternal thymectomy: A case series. PMID- 26257422 TI - Oral ketamine for phantom limb pain: An option for challenging cases. PMID- 26257423 TI - Management of airway in intratracheal tumour surgery. PMID- 26257424 TI - Good vagal tone, a tourniquet and dexmedetomidine: Recipe for disaster. PMID- 26257425 TI - Unilateral pulmonary oedema: Rare manifestation of scorpion sting. PMID- 26257426 TI - Spinal cord surgery in left lateral position with tilt in a pregnant patient with intradural extramedullary Schwannoma. PMID- 26257427 TI - Radiation hazards in operation theatre: Anaesthesiologist's concerns and preventive strategies. PMID- 26257428 TI - Minimising intraoperative exposure of ionising radiation to the anaesthesiologist. PMID- 26257429 TI - Commentary: Minimising intraoperative exposure of ionising radiation to anaesthesiologists. PMID- 26257430 TI - Delayed presentation of post tuberculous broncho oesophageal fistula in an adult: Perioperative anaesthetic management. PMID- 26257431 TI - Perioperative management of a patient with severe Haemophilia B for abdominal pseudotumour Surgery. PMID- 26257432 TI - Opioids induced serotonin toxicity? Think again. PMID- 26257433 TI - Cardiac arrest from tramadol and fentanyl combination. PMID- 26257434 TI - Professional Development for Early Childhood Educators: Efforts to Improve Math and Science Learning Opportunities in Early Childhood Classrooms. AB - Because recent initiatives highlight the need to better support preschool-aged children's math and science learning, the present study investigated the impact of professional development in these domains for early childhood educators. Sixty five educators were randomly assigned to experience 10.5 days (64 hours) of training on math and science or on an alternative topic. Educators' provision of math and science learning opportunities were documented, as were the fall-to spring math and science learning gains of children (n = 385) enrolled in their classrooms. Professional development significantly impacted provision of science, but not math, learning opportunities. Professional development did not directly impact children's math or science learning, although science learning was indirectly affected via the increase in science learning opportunities. Both math and science learning opportunities were positively associated with children's learning. Results suggest that substantive efforts are necessary to ensure that children have opportunities to learn math and science from a young age. PMID- 26257435 TI - Evaluations of bit sleeve and twisted-body bit designs for controlling roof bolter dust. AB - Drilling into coal mine roof strata to install roof bolts has the potential to release substantial quantities of respirable dust. Due to the proximity of drill holes to the breathing zone of roof bolting personnel, dust escaping the holes and avoiding capture by the dust collection system pose a potential respiratory health risk. Controls are available to complement the typical dry vacuum collection system and minimize harmful exposures during the initial phase of drilling. This paper examines the use of a bit sleeve in combination with a dust hog-type bit to improve dust extraction during the critical initial phase of drilling. A twisted-body drill bit is also evaluated to determine the quantity of dust liberated in comparison with the dust-hog-type bit. Based on the results of our laboratory tests, the bit sleeve may reduce dust emissions by one-half during the initial phase of drilling before the drill bit is fully enclosed by the drill hole. Because collaring is responsible for the largest dust liberations, overall dust emission can also be substantially reduced. The use of a twisted-body bit has minimal improvement on dust capture compared with the commonly used dust-hog type bit. PMID- 26257436 TI - Phosphonate-substituted zirconium oxo clusters. AB - ABSTRACT: The phosphonate-substituted zirconium oxo clusters Zr6O2(OBu)12(O3PPh)4 and Zr7O2(OiPr)12(O3PCH2CH2CH2Br)6, with octahedrally coordinated Zr atoms, were synthesized by reaction of zirconium alkoxides with phosphonic acid bis(trimethylsilyl) esters. The basic structural motif are Zr3O(u2-OR)3(OR)3 units which are connected in different ways. GRAPHICAL ABSTRACT: PMID- 26257437 TI - A Nonparametric, Multiple Imputation-Based Method for the Retrospective Integration of Data Sets. AB - Complex research questions often cannot be addressed adequately with a single data set. One sensible alternative to the high cost and effort associated with the creation of large new data sets is to combine existing data sets containing variables related to the constructs of interest. The goal of the present research was to develop a flexible, broadly applicable approach to the integration of disparate data sets that is based on nonparametric multiple imputation and the collection of data from a convenient, de novo calibration sample. We demonstrate proof of concept for the approach by integrating three existing data sets containing items related to the extent of problematic alcohol use and associations with deviant peers. We discuss both necessary conditions for the approach to work well and potential strengths and weaknesses of the method compared to other data set integration approaches. PMID- 26257438 TI - Cook's Distance Measures for Varying Coefficient Models with Functional Responses. AB - The aim of this paper is to develop Cook's distance measures for assessing the influence of both atypical curves and observations under varying coefficient model for functional responses. Our Cook's distance measures include Cook's distances for deleting multiple curves and for deleting multiple grid points, and their scaled Cook's distances. We systematically investigate some theoretical properties of these diagnostic measures. Simulation studies are conducted to evaluate the finite sample properties of these Cook's distances under different scenarios. A real diffusion tensor tract data set is analyzed to illustrate the use of our diagnostic measures. PMID- 26257439 TI - A modified procedure for the palladium catalyzed borylation/Suzuki-Miyaura cross coupling of aryl and heteroaryl halides utilizing bis-boronic acid. AB - A modified Pd-catalyzed method of forming aryl- and heteroarylboron species and a two-step, one-pot borylation/Suzuki-Miyaura cross coupling using the atom economical tetrahydroxydiboron (bis-boronic acid, BBA) is reported. By using ethylene glycol as an additive, the new method results in increased yields, lower BBA loading, faster reaction times, and a broader reaction scope, including previously problematic substrates such as heterocycles. PMID- 26257440 TI - Stereocontrolled enantioselective total synthesis of the [2+2] quadrigemine alkaloids. AB - A unified strategy for enantioselective total synthesis of all stereoisomers of the 2+2 family of quadrigemine alkaloids is reported. In this approach, two enantioselective intramolecular Heck reactions are carried out at the same time on precursors fashioned in four steps from either meso- or (+)-chimonanthine to form the two critical quaternary carbons of the peripheral cyclotryptamine rings of these products. Useful levels of catalyst control are realized in either desymmetrizing a meso precursor or controlling diastereoselectivity in elaborating C2-symmetic intermediates. None of the synthetic quadrigemines are identical with alkaloids isolated previously and referred to as quadrigemines A and E. In addition, we report improvements in our previous total syntheses of (+) or (-)-quadrigemine C that shortened the synthetic sequence to 10 steps and provided these products in 2.2% overall yield from tryptamine. PMID- 26257441 TI - Evolution of a thienopyrimidine antitubercular relying on medicinal chemistry and metabolomics insights. AB - The metabolic instability of an antitubercular small molecule CD117 was addressed through iterative alteration of a key sulfide substituent and interrogation of the effect on growth inhibition of cultured Mycobacterium tuberculosis. This process was informed by studies of the intramycobacterial metabolism of CD117 and its inactive carboxylic acid derivative. Isoxazole 4e and thiazole 4m demonstrated significant gains in mouse liver microsomal stability with slight losses in whole-cell activity. This work illustrates the challenges of antitubercular hit evolution, requiring a balance of chemical and biological insights. PMID- 26257442 TI - Design, Synthesis and Biological Evaluation of beta-Carboline Dimers Based on the Structure of Neokauluamine. AB - The design, synthesis and biological evaluation (anticancer and antimalarial activity) of bis-beta-carbolines, based on the structure of the naturally occurring alkaloid neokauluamine, is described. PMID- 26257443 TI - Conditions for a Rh(I)-catalyzed [2 + 2 + 1] cycloaddition reaction with methyl substituted allenes and alkynes. AB - The direct installation of the C4 and C10 methyl groups present in the 6,12 guaianolide framework using a Rh(I)-catalyzed cyclocarbonylation reaction of methyl subsituted allenes and alkynes is described. High yields of bicyclo[5.3.0]decanes are afforded when low reaction concentrations involving syringe pump addition of the allene-yne to the catalyst are used. PMID- 26257444 TI - Synthesis of the C1-C17 fragment of the archazolids by complex cis-homodimer cross metathesis. AB - A synthesis of the C1-C17 fragment of the archazolids is described featuring a complex cross-metathesis coupling reaction between a cis-homodimer (prepared by silyl-tethered ring-closing metathesis) and the Z,Z-terminal triene containing "eastern domain" of the archazolid natural products. This cross-metathesis was only successful when using the cis- as opposed to the monomer or trans-homodimer, with the cis-dimer added batchwise to minimize cis/trans-isomerization. The product was obtained in an optimized 78% yield using the Hoveyda-Grubbs catalyst at 50 degrees C in toluene. PMID- 26257445 TI - Synthesis and Exploration of Electronically Modified (R)-5,5-Dimethyl-(p-CF3)3-i PrPHOX in Palladium-Catalyzed Enantio- and Diastereoselective Allylic Alkylation: A Practical Alternative to (R)-(p-CF3)3-t-BuPHOX. AB - The synthesis of the novel electronically modified phosphinooxazoline (PHOX) ligand, (R)-5,5-dimethyl-(p-CF3)3-i-PrPHOX, is described. The utility of this PHOX ligand is explored in both enantio- and diastereoselective palladium catalyzed allylic alkylations. These investigations prove (R)-5,5-dimethyl-(p CF3)3-i-PrPHOX to be an effective and cost-efficient alternative to electronically modified PHOX ligands derived from the prohibitively expensive (R) t-leucine. PMID- 26257446 TI - "There's Gotta be Some Give and Take": Community Partner Perspectives on Benefits and Contributions associated with Community Partnerships for Youth. AB - Successful community partnerships for youth are based on the premise that reciprocity exists between all parties, but to what extent is equal power actually present? The current investigation examines the benefits and contributions associated with partnerships from community partners' perspectives. Respondents from 15 different Connect to Protect(r) coalitions initiated by the Adolescent Medicine Trials Network for HIV/AIDS Interventions were interviewed at the onset of their partnerships. Community partners asserted that their contributions to partnerships are more varied than researchers', yet they perceived that researchers acquire more kinds of benefits. Findings indicate nuances regarding reciprocity and power inequities between partners. Community partners' insights have implications for defining best practices within partnerships that benefit youth. PMID- 26257447 TI - A LASSO FOR HIERARCHICAL INTERACTIONS. AB - We add a set of convex constraints to the lasso to produce sparse interaction models that honor the hierarchy restriction that an interaction only be included in a model if one or both variables are marginally important. We give a precise characterization of the effect of this hierarchy constraint, prove that hierarchy holds with probability one and derive an unbiased estimate for the degrees of freedom of our estimator. A bound on this estimate reveals the amount of fitting "saved" by the hierarchy constraint. We distinguish between parameter sparsity the number of nonzero coefficients-and practical sparsity-the number of raw variables one must measure to make a new prediction. Hierarchy focuses on the latter, which is more closely tied to important data collection concerns such as cost, time and effort. We develop an algorithm, available in the R package hierNet, and perform an empirical study of our method. PMID- 26257448 TI - Innovation indices: the need for positioning them where they properly belong. AB - A specific quality of the discussion about innovation indices (scoreboards) is that more often than not the subject is dealt with from a purely technical point of view. Such a narrow approach silently assumes that indices used as a policy tool are an accurate reflection of the phenomenon and should not be questioned, and also that the whole discussion concerning them should refer to methodological aspects and is best left to the statisticians. This author is of the opinion that for an accurate evaluation of the value of indices as a policy tool, it is necessary to consider the matter from the broader point of view and from the context in which such indices are generated and used. This article puts forward the thesis that progress in science and innovation policy studies depends on a diversity of issues, approaches and perspectives. If that is the case, maintaining thematic and methodological variety may be more important than creating coherent and closed analytical tools, i.e. indices. The advantage of indices is that they focus attention on those variables which are deemed to be key. Among their disadvantages, however, are their highly abstract nature (in order to understand innovation-related phenomena, it is necessary to study them in tangible, composite forms); their tendency to skip unmeasurable determinants; their prior acceptance of definitions and concepts of innovation (instead of searching for them); the way they apply a single yardstick to diverse countries and regions, assumed linearity and causality in a complex and non-linear world, the way they direct policy towards implementing indicators (rather than identifying and solving problems). It is suggested that big data revolution will allow the emergence of a new measurement tools that will replace innovation indices. PMID- 26257449 TI - Citation success of different publication types: a case study on all references in psychology publications from the German-speaking countries (D-A-CH-L-L) in 2009, 2010, and 2011. AB - Scientometric data on the citation success of different publication types and publication genres in psychology publications are presented. Data refer to references that are cited in these scientific publications and that are documented in PSYNDEX, the exhaustive database of psychology publications from the German-speaking countries either published in German or in English language. Firstly, data analyses refer to the references that are cited in publications of 2009 versus 2010 versus 2011. With reference to all cited references, the portion of journal articles ranges from 57 to 61 %, of books from 22 to 24 %, and of book chapters from 14 to 15 %, with a rather high stability across the three publication years analysed. Secondly, data analyses refer to the numbers of cited references from the German-speaking countries, which are also documented in PSYNDEX. These compose about 11 % of all cited references indicating that nearly 90 % of the references cited are of international and/or interdisciplinary publications not stemming from the German-speaking countries. The subsample shows the proportion of journal articles, books, and chapters, and these are very similar to the percentages identified for all references that are cited. Thirdly, analyses refer to document type, scientific genre, and psychological sub discipline of the most frequently cited references in the psychology publications. The frequency of top-cited references of books and book chapters is almost equal to that of journal articles; two-thirds of the top-cited references are non-empirical publications, only one-third are empirical publications. Top cited references stem particularly from clinical psychology, experimental psychology, as well as tests, testing and psychometrics. In summary, the results point to the fact that citation analyses, which are limited to journal papers, tend to neglect very high portions of references that are cited in scientific publications. PMID- 26257450 TI - GEOGRAPHICALLY-WEIGHTED REGRESSION ANALYSIS OF PERCENTAGE OF LATE-STAGE PROSTATE CANCER DIAGNOSIS IN FLORIDA. AB - This study assessed spatial context and the local impacts of putative factors on the proportion of prostate cancer diagnosed at late-stages in Florida during the period 2001-2007. A logistic regression was performed aspatially and by geographically-weighted regression (GWR) at the nodes of a 5 km spacing grid overlaid over Florida and using all the cancer cases within a radius of 125 km of each node. Variables associated significantly with high percentages of late-stage prostate cancer included having comorbidities, smoking, being Black and living in census tracts with farmhouses. Having private or public insurance, being married or diagnosed in a for-profit facility, as well as living in census tracts with high household income reduced significantly this likelihood. Geographically weighted regression allowed the identification of areas where the local odds ratio is significantly different from the ratio estimated using aspatial regression (State-level). For example, the local odds ratios for the comorbidity covariates were significantly smaller than the State-level odds ratio in Tallahassee and Pensacola, while they were significantly larger in Palm Beach. This emphasizes the need for local strategies and cancer control interventions to reduce the percentage of prostate cancer diagnosed at late-stages and ultimately eliminate health disparities. PMID- 26257451 TI - Hierarchical Clustering With Prototypes via Minimax Linkage. AB - Agglomerative hierarchical clustering is a popular class of methods for understanding the structure of a dataset. The nature of the clustering depends on the choice of linkage-that is, on how one measures the distance between clusters. In this article we investigate minimax linkage, a recently introduced but little studied linkage. Minimax linkage is unique in naturally associating a prototype chosen from the original dataset with every interior node of the dendrogram. These prototypes can be used to greatly enhance the interpretability of a hierarchical clustering. Furthermore, we prove that minimax linkage has a number of desirable theoretical properties; for example, minimax-linkage dendrograms cannot have inversions (unlike centroid linkage) and is robust against certain perturbations of a dataset. We provide an efficient implementation and illustrate minimax linkage's strengths as a data analysis and visualization tool on a study of words from encyclopedia articles and on a dataset of images of human faces. PMID- 26257452 TI - Bayesian Inference for Multivariate Meta-regression with a Partially Observed Within-Study Sample Covariance Matrix. AB - Multivariate meta-regression models are commonly used in settings where the response variable is naturally multi-dimensional. Such settings are common in cardiovascular and diabetes studies where the goal is to study cholesterol levels once a certain medication is given. In this setting, the natural multivariate endpoint is Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Triglycerides (TG) (LDL-C, HDL-C, TG). In this paper, we examine study level (aggregate) multivariate meta-data from 26 Merck sponsored double-blind, randomized, active or placebo-controlled clinical trials on adult patients with primary hypercholesterolemia. Our goal is to develop a methodology for carrying out Bayesian inference for multivariate meta-regression models with study level data when the within-study sample covariance matrix S for the multivariate response data is partially observed. Specifically, the proposed methodology is based on postulating a multivariate random effects regression model with an unknown within-study covariance matrix Sigma in which we treat the within-study sample correlations as missing data, the standard deviations of the within-study sample covariance matrix S are assumed observed, and given Sigma, S follows a Wishart distribution. Thus, we treat the off-diagonal elements of S as missing data, and these missing elements are sampled from the appropriate full conditional distribution in a Markov chain Monte Carlo (MCMC) sampling scheme via a novel transformation based on partial correlations. We further propose several structures (models) for Sigma, which allow for borrowing strength across different treatment arms and trials. The proposed methodology is assessed using simulated as well as real data, and the results are shown to be quite promising. PMID- 26257453 TI - Optimal Estimation and Rank Detection for Sparse Spiked Covariance Matrices. AB - This paper considers a sparse spiked covariancematrix model in the high dimensional setting and studies the minimax estimation of the covariance matrix and the principal subspace as well as the minimax rank detection. The optimal rate of convergence for estimating the spiked covariance matrix under the spectral norm is established, which requires significantly different techniques from those for estimating other structured covariance matrices such as bandable or sparse covariance matrices. We also establish the minimax rate under the spectral norm for estimating the principal subspace, the primary object of interest in principal component analysis. In addition, the optimal rate for the rank detection boundary is obtained. This result also resolves the gap in a recent paper by Berthet and Rigollet [2] where the special case of rank one is considered. PMID- 26257454 TI - Relations between Fathers' and Mothers' Infant Engagement Patterns in Dual-Earner Families and Toddler Competence. AB - This study examined the trajectories of time new fathers and mothers in dual earner families (N = 178) reported spending in developmentally appropriate positive engagement activities over the first 9 months of their child's life on both work and non-workdays. We also explored how paternal and maternal engagement patterns in infancy were associated with children's later social-emotional competence during toddlerhood (M = 25 months). Utilizing latent growth models, we found that, compared with mothers, fathers spent significantly less time engaging with their infants; however, both parents increased their engagement over time at relatively the same rate. Fathers' rate of increase over time and mothers' initial starting point of engagement on non-workdays were associated with toddlers' attention and mastery motivation. Findings are discussed with regards to what they mean for dual-earner couples and fathers' investment in their offspring, highlighting what they may imply about the second demographic transition and family functioning. PMID- 26257455 TI - Language Disorders in Multilingual and Multicultural Populations. AB - We review the characteristics of developmental language disorders (primary language impairment, reading disorders, autism, Down syndrome) and acquired language disorders (aphasia, dementia, traumatic brain injury) among multilingual and multicultural individuals. We highlight the unique assessment and treatment considerations pertinent to this population, including, for example, concerns of language choice and availability of measures and of normative data in multiple languages. A summary of relevant, recent research studies is provided for each of the language disorders selected. PMID- 26257456 TI - Prophylactic Treatments for Anomia in the Logopenic Variant of Primary Progressive Aphasia: Cross-Language Transfer. AB - BACKGROUND: Treatment studies for anomia in PPA have rarely compared multiple treatments in the same individual, and few anomia treatment studies have included participants with the logopenic variant of PPA (lvPPA). AIMS: The goals of this study were to evaluate two types of treatment for anomia in a bilingual participant (ND) with lvPPA, and to examine possible cross-language transfer of treatment effects. METHODS & PROCEDURES: ND is a Norwegian-English bilingual woman with lvPPA who began this study at the age of 69. In the phonological treatment, ND listened to a word while viewing a corresponding picture, and she repeated the word. In the orthographic treatment, ND read a word out loud while viewing the corresponding picture, and she then copied the word. Both treatments were conducted in English, and accuracy for three tasks (oral naming, written naming, and naming to definition) was assessed in English and Norwegian. The treatment occurred over a one-year period, with eight sessions at the laboratory during the first month, followed by monthly laboratory sessions and thrice-weekly home practice sessions during the subsequent 11 months. Post-treatment assessments were conducted at 1 week, 8 months, 1 year, 20 months, and 3 years. OUTCOMES & RESULTS: Compared to untrained items, the orthographic treatment resulted in greater English written naming accuracy. This treatment also resulted in cross-language transfer: greater Norwegian oral naming and naming to definition accuracy. The phonological treatment resulted in marginally greater English oral naming accuracy, but it did not have a significant effect on naming accuracy in Norwegian. CONCLUSIONS: These findings suggest that the orthographic treatment was effective in strengthening the orthographic representations of the treated items, which facilitated ND's written naming performance. The pattern of cross-language transfer suggests that the orthographic treatment also strengthened the language-independent semantic representations of the treated items, thereby facilitating access to their Norwegian phonological representations. PMID- 26257457 TI - Understanding the Educational Attainment of Sexual Minority Women and Men. AB - National studies have not analyzed sexual identity disparities in high school completion, college enrollment, or college completion in the United States. Using Add Health data, we document the relationship between adult sexual orientation and each of these outcomes. Many sexual minority respondents experienced disadvantages in adolescent academic achievement, school experiences, and social environments. This translates into educational attainment in complex, gendered ways. We find that the socially privileged completely heterosexual identity predicts higher educational attainment for women, while for men it is often a liability. Mostly heterosexual and gay identities are educationally beneficial for men but not women. There are college completion disparities between gay and mostly heterosexual women and their completely heterosexual counterparts. Bisexual respondents, especially women, have particularly problematic outcomes. Adolescent experiences, attitudes, and social contexts explain some of these differences. From adolescence through college, sexual minority groups, but especially females, need intervention to reduce substantial educational disparities. PMID- 26257458 TI - Enzymatic Glucose Sensor Compensation for Variations in Ambient Oxygen Concentration. AB - Due to the increasing prevalence of diabetes, research toward painless glucose sensing continues. Oxygen sensitive phosphors with glucose oxidase (GOx) can be used to determine glucose levels indirectly by monitoring oxygen consumption. This is an attractive combination because of its speed and specificity. Packaging these molecules together in "smart materials" for implantation will enable non invasive glucose monitoring. As glucose levels increase, oxygen levels decrease; consequently, the luminescence intensity and lifetime of the phosphor increase. Although the response of the sensor is dependent on glucose concentration, the ambient oxygen concentration also plays a key role. This could lead to inaccurate glucose readings and increase the risk of hyper- or hypoglycemia. To mitigate this risk, the dependence of hydrogel glucose sensor response on oxygen levels was investigated and compensation methods explored. Sensors were calibrated at different oxygen concentrations using a single generic logistic equation, such that trends in oxygen-dependence were determined as varying parameters in the equation. Each parameter was found to be a function of oxygen concentration, such that the correct glucose calibration equation can be calculated if the oxygen level is known. Accuracy of compensation will be determined by developing an overall calibration, using both glucose and oxygen sensors in parallel, correcting for oxygen fluctuations in real time by intentionally varying oxygen, and calculating the error in actual and predicted glucose levels. While this method was developed for compensation of enzymatic glucose sensors, in principle it can also be implemented with other kinds of sensors utilizing oxidases. PMID- 26257459 TI - Hemoglobin A1c Level Is Not Related to the Severity of Atherosclerosis in Patients with Acute Coronary Syndrome. AB - BACKGROUND: The relationship between hemoglobin A1c (HbA1c) levels and the extent of coronary artery stenosis in patients with acute coronary syndrome (ACS) remains uncertain. The present study aimed to assess the correlation of HbA1c level with angiographic coronary atherosclerosis. METHODS: 292 consecutive ACS patients were enrolled and stratified into three groups according to HbA1c levels (group 1: < 6.0%, n = 137; group 2: 6.0-6.4%, n = 67; group 3: >= 6.5%, n = 88). The severity of coronary arteriosclerosis was assessed by Gensini score. The relationship between HbA1c and Gensini score was analyzed by multiple variables analysis. RESULTS: HbA1c level was not associated with the severity of CAD assessed by Gensini score in patients with ACS, even after the adjustment for other risk factors. However, NT-proBNP, ApoA1 and LVEF levels were independent predictors for CAD severity. Moreover, HbA1c level was not associated with the risk of high Gensini score (> 40) by logistic regression analysis. Diabetes mellitus (DM) and LVEF levels were two independent risk factors for high Gensini score. CONCLUSIONS: HbA1c level is not a significant and independent marker for the severity of angiography in ACS patients, even in high-risk patients. PMID- 26257460 TI - Electrocardiographic Predictors of Cardiovascular Mortality. AB - Cardiovascular diseases are the main causes of mortality. Sudden cardiac death may also appear in athletes, due to underlying congenital or inherited cardiac abnormalities. The electrocardiogram is used in clinical practice and clinical trials, as a valid, reliable, accessible, inexpensive method. The aim of the present paper was to review electrocardiographic (ECG) signs associated with cardiovascular mortality and the mechanisms underlying those associations, providing a brief description of the main studies in this area, and consider their implication for clinical practice in the general population and athletes. The main ECG parameters associated with cardiovascular mortality in the present paper are the P wave (duration, interatrial block, and deep terminal negativity of the P wave in V1), prolonged QT and Tpeak-Tend intervals, QRS duration and fragmentation, bundle branch block, ST segment depression and elevation, T waves (inverted, T wave axes), spatial angles between QRS and T vectors, premature ventricular contractions, and ECG hypertrophy criteria. PMID- 26257461 TI - Association of DNA Repair Gene APE1 Asp148Glu Polymorphism with Breast Cancer Risk. AB - OBJECTIVE: The aim of this study was to investigate the role of APE1 Asp148Glu polymorphism in breast cancer progression in Saudi population. METHODS: We examined the genetic variations (rs1130409) in the DNA base excision repair gene APE1 at codon 148 (Asp148Glu) and its association with breast cancer risk using genotypic assays and in silico structural as well as functional predictions. In silico structural analysis was performed with Asp148Glu allele and compared with the predicted native protein structure. The wild and mutant 3D structures of APE1 were compared and analyzed using solvent accessibility models for protein stability confirmation. RESULTS: Genotypic analysis of APE1 (rs1130409) showed statistically significant association of Asp148Glu with elevated susceptibility to breast cancer. The in silico analysis results indicated that the nsSNP Asp148Glu may cause changes in the protein structure and is associated with breast cancer risk. CONCLUSION: Taken together, this is the first report that established that Asp148Glu variant has structural and functional effect on the APE1 and may play an important role in breast cancer progression in Saudi population. PMID- 26257462 TI - Toll-Like Receptor 9 Inactivation Alleviated Atherosclerotic Progression and Inhibited Macrophage Polarized to M1 Phenotype in ApoE-/- Mice. AB - OBJECTIVE: Toll-like receptor 9 (TLR9) is involved in many inflammatory diseases, but its role in atherosclerosis remains controversial. This study aimed to investigate the role of TLR9 in atherosclerosis development and macrophage polarization. METHODS: ApoE(-/-) mice were treated with vehicle or IRS869 for 12 weeks. Plaque vulnerability was assessed with immunohistochemical analysis, picro sirius red, and oil red O staining. The expressions of M1- and M2-associated markers in plaques were detected by RT-PCR and immunofluorescence. The aorta TLR9 and its downstream molecules including myeloid differentiation protein 88 (MyD88), phosphorylated nuclear factor-kappa B (p-NF-kappaB), and interferon regulatory factor 7 (IRF7) were determined by western blot analysis. The frequency of M1 and M2 subtype in RAW264.7 cells treated with IRS869 and/or ODN1826 was evaluated with flow cytometry. RESULTS: In ApoE(-/-) mice, functional inactivation of TLR9 pathway resulted in attenuated atherosclerosis development, as manifested by reduced plaque burden and by decreased plaque vulnerability. Mechanistically, TLR9 inhibition prevented the activation of MyD88/NF-kappaB pathway and shifted the balance of M1/M2 toward M2 macrophages that were involved. CONCLUSIONS: Our data indicated that TLR9 inactivation ameliorated atherosclerosis via skewing macrophage plasticity to M2 phenotype in ApoE deficient mice. These findings may provide a promising therapeutic strategy for atherosclerosis. PMID- 26257463 TI - Characteristics of Three-Dimensional Power Doppler in Gestational Trophoblastic Disease. AB - PURPOSE: In the present study, the three-dimensional power Doppler was used as a quantitative method to evaluate its reliability in detecting and assessing of gestational trophoblastic disease (GTD). METHODS: 52 GTD patients who received diagnosis and treatment at the first affiliated hospitals of Xi'an Jiaotong University in China between 2011 and 2013 were evaluated using Voluson E8 (GE Medical System). Demographic information, pathological characteristics, clinical history, sonographic images, and related indices (resistance index, vascularization index, and flow and vascularization index) were evaluated. RESULT: Three-dimension power Doppler indicated that there were significant differences in the resistance index, vascularization index, flow index, and vascularization-flow index between the healthy individuals and each subgroup of patients (P < 0.01). Further, in combining invasive hydatidiform mole and choriocarcinoma groups, there was a significant difference between hydatidiform mole and the combined malignant group (P < 0.01). And the abnormal sonographic and power Doppler findings in GTD were resolved when chemotherapy was done successfully. CONCLUSION: Combined with the clinical features, sonography and three-dimension power Doppler imaging were helpful in diagnosing GTD as a noninvasive method, distinguishing the invasive nature of disease, detecting the recurrence of the disease, and assessing the effectiveness of the chemotherapy. PMID- 26257464 TI - Molecular Dynamics Simulation and NMR Investigation of the Association of the beta-Blockers Atenolol and Propranolol with a Chiral Molecular Micelle. AB - Molecular dynamics simulations and NMR spectroscopy were used to compare the binding of two beta-blocker drugs to the chiral molecular micelle poly-(sodium undecyl-(L)-leucine-valine). The molecular micelle is used as a chiral selector in capillary electrophoresis. This study is part of a larger effort to understand the mechanism of chiral recognition in capillary electrophoresis by characterizing the molecular micelle binding of chiral compounds with different geometries and charges. Propranolol and atenolol were chosen because their structures are similar, but their chiral interactions with the molecular micelle are different. Molecular dynamics simulations showed both propranolol enantiomers inserted their aromatic rings into the molecular micelle core and that (S) propranolol associated more strongly with the molecular micelle than (R) propranolol. This difference was attributed to stronger molecular micelle hydrogen bonding interactions experienced by (S)-propranolol. Atenolol enantiomers were found to bind near the molecular micelle surface and to have similar molecular micelle binding free energies. PMID- 26257465 TI - ALCOHOL-INVOLVED RAPES: ARE THEY MORE VIOLENT? AB - Alcohol's psychological, cognitive, and motor effects contribute to rape. Based on theory and past research, we hypothesized that there would be a curvilinear relationship between the quantity of alcohol consumed by perpetrators and how aggressively they behaved. Moderate levels of intoxication encourage aggressiveness; however, extreme levels severely inhibit cognitive and motor capacity. We also hypothesized that victims' alcohol consumption would have a curvilinear relationship to their resistance. These hypotheses were examined with data from 132 college women who had been the victims of attempted or completed rape. Although there was a curvilinear result for perpetrators, the slope of the curve suggested that aggressiveness was worst when no alcohol or the highest levels of alcohol were consumed. There was a negative linear relationship between victims' alcohol consumption and resistance. Difficulties associated with accurately assessing degree of intoxication from survey data are discussed and suggestions are made for improving alcohol measurement in rape research. PMID- 26257466 TI - SIMILARITIES AND DIFFERENCES IN WOMEN'S SEXUAL ASSAULT EXPERIENCES BASED ON TACTICS USED BY THE PERPETRATOR. AB - Only a few studies have examined the characteristics of sexual assault based on the tactics used by the perpetrator. In this study we compared the experiences of women who were forced to engage in vaginal, anal, or oral intercourse due to verbal coercion, physical force, or intoxication. Random-digit dialing was used to obtain a sample of 272 single African American and Caucasian women between the ages of 18 and 49 from the Detroit metropolitan area. Participants completed a computer-assisted self-interview that asked detailed questions about a past sexual assault and their reactions to it. Among the 139 women who were forced to engage in vaginal, anal, or oral intercourse, sexual assaults that involved physical force produced the most severe negative outcomes. Situations that involved the woman being too intoxicated to resist differed from others primarily in terms of how much alcohol the man and woman consumed. Although all types of sexual assault were perceived as being at least moderately serious, verbally coerced assaults were on average perceived as being least serious. These findings suggest that the perpetrators' tactics affect women's responses to sexual assault. PMID- 26257467 TI - Distribution of algal aggregates under summer sea ice in the Central Arctic. AB - The sea ice cover of the Arctic Ocean has changed dramatically in the last decades, and the resulting consequences for the sea-ice-associated ecosystem remain difficult to assess. Algal aggregates underneath sea ice are of great importance for the ice-associated ecosystem and the pelagic-benthic coupling. However, the frequency and distribution of their occurrence is not well quantified. During the IceArc expedition (ARK-27/3) of RV Polarstern in late summer 2012, we observed different types of algal aggregates floating underneath various ice types in the Central Arctic basins. We investigated the spatial distribution of ice algal aggregates and quantified their biomass, using under ice image surveys obtained by an upward-looking camera on a remotely operated vehicle. On basin scale, filamentous aggregates of Melosira arctica are more frequently found in the inner part of the Central Arctic pack ice, while rounded aggregates mainly formed by pennate diatoms are found closer to the ice edge, under melting sea ice. On the scale of an ice floe, the distribution of algal aggregates in late summer is mainly regulated by the topography of the ice underside, with aggregates accumulating in dome-shaped structures and at the edges of pressure ridges. The average biomass of the aggregates from our sites and season was 0.1-6.0 mg C m-2. However, depending on the approach used, differences in orders of magnitude for biomass estimates may occur. This highlights the difficulties of upscaling observations and comparing results from surveys conducted using different methods or on different spatial scales. PMID- 26257468 TI - A noise control package for vibrating screens. AB - Hearing loss was the second-most common illness reported to the Mine Safety and Health Administration (MSHA) in 2009. Furthermore, between 2000 and 2010, 30% of all noise-related injury complaints reported to MSHA were for coal preparation plant employees. Previous National Institute for Occupational Safety and Health (NIOSH) studies have shown that vibrating screens are key noise sources to address in order to reduce coal preparation plant noise. In response, NIOSH researchers have developed a suite of noise controls for vibrating screens consisting of constrained layer damping (CLD) treatments, a tuned mechanism suspension, an acoustic enclosure, and spring inserts. Laboratory testing demonstrates that this noise control suite reduces the A-weighted sound power level of the vibrating screen by 6 dB. To provide a comparison to laboratory results and prove durability, field testing of two noise controls was performed on a vibrating screen in a working coal preparation plant. The spring inserts and CLD treatments were selected due to their ease of installation and practicability. Field testing of these controls yielded reductions that were comparable to laboratory results. PMID- 26257469 TI - The effect of contextual constraint on parafoveal processing in reading. AB - Semantic preview benefit in reading is an elusive and controversial effect because empirical studies do not always (but sometimes) find evidence for it. Its presence seems to depend on (at least) the language being read, visual properties of the text (e.g., initial letter capitalization), the type of relationship between preview and target, and as shown here, semantic constraint generated by the prior sentence context. Schotter (2013) reported semantic preview benefit for synonyms, but not semantic associates when the preview/target was embedded in a neutral sentence context. In Experiment 1, we embedded those same previews/targets into constrained sentence contexts and in Experiment 2 we replicated the effects reported by Schotter (2013; in neutral sentence contexts) and Experiment 1 (in constrained contexts) in a within-subjects design. In both experiments, we found an early (i.e., first-pass) apparent preview benefit for semantically associated previews in constrained contexts that went away in late measures (e.g., total time). These data suggest that sentence constraint (at least as manipulated in the current study) does not operate by making a single word form expected, but rather generates expectations about what kinds of words are likely to appear. Furthermore, these data are compatible with the assumption of the E-Z Reader model that early oculomotor decisions reflect "hedged bets" that a word will be identifiable and, when wrong, lead the system to identify the wrong word, triggering regressions. PMID- 26257470 TI - Predicting Anxiety Diagnoses and Severity with the CBCL-A: Improvement Relative to Other CBCL Scales? AB - The Child Behavior Checklist (CBCL) is a widely used parent-report of child and adolescent behavior. We examined the ability of the CBCL-A scale, a previously published subset of CBCL items, to predict the presence of generalized anxiety disorder (GAD), separation anxiety disorder (SAD), and social phobia (SoP), as well as anxiety severity, among 488 youth randomized in the Child Anxiety Multimodal Study (CAMS). We predicted that the CBCL-A's unique inclusion of items related to somatic symptoms would better identify anxiety disorder and severity than other CBCL scales, given that somatic complaints are often key features of anxiety among youth. Results support the use of the anxiety-based CBCL subscales as first-line screeners for generally elevated symptoms of anxiety, rather than tools to identify specific anxiety disorders. Although somatic symptoms are often reported and included in diagnostic criteria for certain anxiety disorders (e.g., SAD, GAD), the unique combination of somatic and non-somatic symptoms for the CBCL-A subscale did not increase its ability to consistently predict the presence of specific anxiety disorders. PMID- 26257471 TI - The nature of the language input affects brain activation during learning from a natural language. AB - Artificial language studies have demonstrated that learners are able to segment individual word-like units from running speech using the transitional probability information. However, this skill has rarely been examined in the context of natural languages, where stimulus parameters can be quite different. In this study, two groups of English-speaking learners were exposed to Norwegian sentences over the course of three fMRI scans. One group was provided with input in which transitional probabilities predicted the presence of target words in the sentences. This group quickly learned to identify the target words and fMRI data revealed an extensive and highly dynamic learning network. These results were markedly different from activation seen for a second group of participants. This group was provided with highly similar input that was modified so that word learning based on syllable co-occurrences was not possible. These participants showed a much more restricted network. The results demonstrate that the nature of the input strongly influenced the nature of the network that learners employ to learn the properties of words in a natural language. PMID- 26257472 TI - Social Attitudes toward Cerebral Palsy and Potential Uses in Medical Education Based on the Analysis of Motion Pictures. AB - This study presents how motion pictures illustrate a person with cerebral palsy (CP), the social impact from the media, and the possibility of cerebral palsy education by using motion pictures. 937 motion pictures were reviewed in this study. With the criteria of nondocumentary movies, possibility of disability classification, and availability, the total number of motion pictures about CP was reduced to 34. The geographical distribution of movie number ever produced is as follows: North America 12, Europe 11, India 2, East Asia 6, and Australia 3. The CP incidences of different motor types in real world and in movies, respectively, are 78-86%, 65% (Spastic); 1.5-6%, 9% (Dyskinetic); 6.5-9%, 26% (Mixed); 3%, 0% (Ataxic); 3-4%, 0% (Hypotonic). The CP incidences of different Gross Motor Function Classification System (GMFCS) levels in real world and in movies, respectively, are 40-51%, 47% (Level I + II); 14-19%, 12% (Level III); 34 41%, 41% (Level IV + V). Comparisons of incidence between the real world and the movies are surprisingly matching. Motion pictures honestly reflect the general public's point of view to CP patients in our real world. With precise selection and medical professional explanations, motion pictures can play the suitable role making CP understood more clearly. PMID- 26257473 TI - Saliency-aware food image segmentation for personal dietary assessment using a wearable computer. AB - Image-based dietary assessment has recently received much attention in the community of obesity research. In this assessment, foods in digital pictures are specified, and their portion sizes (volumes) are estimated. Although manual processing is currently the most utilized method, image processing holds much promise since it may eventually lead to automatic dietary assessment. In this paper we study the problem of segmenting food objects from images. This segmentation is difficult because of various food types, shapes and colors, different decorating patterns on food containers, and occlusions of food and non food objects. We propose a novel method based on a saliency-aware active contour model (ACM) for automatic food segmentation from images acquired by a wearable camera. An integrated saliency estimation approach based on food location priors and visual attention features is designed to produce a salient map of possible food regions in the input image. Next, a geometric contour primitive is generated and fitted to the salient map by means of multi-resolution optimization with respect to a set of affine and elastic transformation parameters. The food regions are then extracted after contour fitting. Our experiments using 60 food images showed that the proposed method achieved significantly higher accuracy in food segmentation when compared to conventional segmentation methods. PMID- 26257475 TI - Personality and health: Road to well-being. PMID- 26257474 TI - Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) Downregulates the Expression of Protumor Factors Cyclooxygenase-2 and Inducible Nitric Oxide Synthase in a GM-CSF Receptor-Independent Manner in Cervical Cancer Cells. AB - Enhanced expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) is associated with the pathogenic processes of various tumor types. COX-2 and iNOS expression in the immunomodulatory dendritic cells is mediated by the granulocyte macrophage-colony stimulating factor (GM-CSF), which is also expressed by cervical cancer cells; however, whether and how GM-CSF regulates COX-2 and iNOS expression in clinical cervical cancer cells remain unknown. In this study, we found that the COX-2 and iNOS expression was upregulated in the cervical cancer tissues and positively correlated with cancer metastasis and stage. About one-half of the cervical cancer tissues showed strong/moderate GM-CSF expression, while the normal cervical tissues showed >80% positive rate; no GM-CSFR protein was detectable on the cervical cancer cells. The GM-CSF expression was negatively correlated with the COX-2 and iNOS expression in the cervical cancer tissues and the functional negative regulatory effect of GM-CSF on COX-2/iNOS expression was demonstrated in various cervical cancer cell lines. Therefore, in cervical cancer cells, GM-CSF might contribute an antitumor response by inhibiting iNOS and COX-2 expression in a GM-CSFR independent manner. PMID- 26257476 TI - Coping among the caregivers of patients with schizophrenia. AB - Coping is understood as the process of managing external or internal demands that are considered as taxing or exceeding the resources of the person. There is no formal classification of coping strategies, and these are understood as adaptive versus maladaptive and problem focuses versus emotion-focused. Understanding the commonly used coping strategies in a particular group of subjects can provide valuable insights for designing interventions to reduce the stress. In this review, we look at the literature which is available with regards to the coping strategies used by the caregivers of patients with schizophrenia. Findings suggest that caregivers of patients with schizophrenia use mixed type of coping mechanisms to deal with the stress of caregiving. The coping strategies are shown to have association with variables such as caregiver burden, caregiving experience, expressed emotions, social support, psychological morbidity in the caregivers, quality of life of caregivers and psychopathology in patients. One of the major limitations of the literature is that there is a lot of variability in the assessment instruments used across different studies to assess coping. PMID- 26257477 TI - Fatigue management in the workplace. AB - Workers' fatigue is a significant problem in modern industry, largely because of high demand jobs, long duty periods, disruption of circadian rhythms, and accumulative sleep debt that are common in many industries. Fatigue is the end result of integration of multiple factors such as time awake, time of day, and workload. Then, the full understanding of circadian biologic clock, dynamics of transient and cumulative sleep loss, and recovery is required for effective management of workplace fatigue. It can be more investigated in a new field of sleep medicine called occupational sleep medicine. Occupational sleep medicine is concerned with maintaining best productivity and safety in the industrial settings. The fatigue risk management system (FRMS) is a comprehensive approach that is based on applying scientific evidence of sleep knowledge to manage workers fatigue. It is developing rapidly in the highly safety demand jobs; especially truck drivers, pilots, and power plant workers. The objective of this review is to explain about fatigue in the workplace with emphasis on its association work performance and errors/accidents. Also, we discussed about different methods of fatigue measurement and management. PMID- 26257478 TI - The hippocampus and executive functions in depression. AB - BACKGROUND: The relationship between depression, hippocampus (HC), and executive dysfunctions seems complex and has been the focus of research. Recent evidence indicates a possible role of HC in executive dysfunction seen in depression. No such studies on Indian population have been done. AIM: To look for changes in HC and executive functions in depression. SETTINGS AND DESIGN: A cross-sectional analytical controlled study. Sample size 50 (controls 50). MATERIALS AND METHODS: Hippocampal volume and executive dysfunction was measured using structural magnetic resonance imaging (MRI) and Wisconsin Card Sorting Test (WCST), respectively. Findings on these two parameters were compared between depressives and healthy matched controls as well as between first episode (FE) and recurrent depressives and across the severity of depression (mild, moderate, and severe). STATISTICAL ANALYSIS: Statistical Package for Social Sciences (SPSS) version 17 was used for analysis. Normally distributed continuous variables were analyzed with independent t-tests. Analysis of variance (ANOVA) was used for multiple comparisons. Categorical data were compared with chi(2) or Fisher's exact test. Clinical correlations were conducted using Pearson correlations. RESULT: Depressed patients had a smaller left (Lt) hippocampal volume as well as poor performance on several measures of executive functions. Smaller hippocampal volume was found even in FE. Those who had a past burden of depressive illness had an even smaller hippocampal volume. No direct correlation was found between the HC volume and cognitive dysfunction. CONCLUSION: Depressive illness appears to be toxic to the HC. The relationship between HC and executive dysfunction in depression may be indirect through its functional connections. PMID- 26257479 TI - Depression, anxiety and stress levels in industrial workers: A pilot study in Bangalore, India. AB - BACKGROUND: Mental health disorders affect around 500 million people worldwide. In India, around 10-12% of people are affected by a mental disorder either due to stress, depression, anxiety, or any other cause. Mental health of workers affects the productivity of the workplace, with estimates putting these losses to be over 100 million dollars annually. AIMS: The study aims to measure depression, anxiety, and stress levels of workers in an industry and to investigate if it has any effect on productivity of the firm. MATERIALS AND METHODS: The study utilized a cross-sectional design and was conducted among workmen of the firm. A sociodemographic based questionnaire and a mental health screening tool Depression Anxiety Stress Scale (DASS)-21 were used for the same. A total of 90 completed questionnaires were analyzed for the study. The data was analyzed for central tendencies as well as for any associations and correlations. RESULTS: The study showed that none of the workers had a positive score for depression. It also showed that around 36% of the workers had a positive score for anxiety and 18% of the workers had a positive score for stress on DASS-21 scale. The odds ratio between stress and number of leaves taken by a worker in the last 3 months suggested a dose-response relationship, but was statistically insignificant. CONCLUSION: The study found a prevalence rate of around 18-36% for anxiety and stress amongst the workers at the factory. Large-scale studies will help understand the effect mental health status has on the Indian workplace. PMID- 26257480 TI - Co-relationship between sexual dysfunction and high-risk sexual behavior in patients receiving buprenorphine and naltrexone maintenance therapy for opioid dependence. AB - INTRODUCTION: People suffering from substance dependence suffer from various sexual dysfunctions and are at risk for indulging in various high-risk sexual behaviors and thus are vulnerable to acquire various infections such as HIV/AIDS and other sexually transmitted infections. AIM: The aim of the study was to evaluate the correlation between sexual dysfunction and high-risk sexual behavior in opioid-dependent men receiving buprenorphine and naltrexone maintenance therapy. MATERIALS AND METHODS: Semi-structured questionnaire, brief male sexual functioning inventory and HIV-risk taking behavior scale was administered to a sample of 60 sexually active men, receiving buprenorphine (n = 30) and naltrexone (n = 30) maintenance therapy for opioid dependence. RESULTS: The main outcomes are correlation between severity of sexual dysfunction and HIV-risk taking behavior. The study results showed 83% of the men on buprenorphine and 90% on naltrexone reported at least one of the sexual dysfunction symptoms. There was a negative correlation between sexual dysfunction and HIV-risk taking behavior that suggest severe the dysfunction, higher the risk taking behavior. Significant correlation was present with overall sexual dysfunction and HIV-risk taking behavior (P = 0.028 and in naltrexone receiving group premature ejaculation versus HIV-risk taking behavior however, (P = 0.022, P < 0.05) there were no significant differences among both the groups except above findings. CONCLUSION: Conclusion was treatment is associated with sexual dysfunctions and HIV-risk taking behavior, which has clinical implication. Future research should explore this further using biochemical analyses. PMID- 26257481 TI - A Study of personality profile and criminal behavior in substance abusers. AB - AIM: The aim of the present study was to study the personality characteristics and criminal behavior in the substance abusers. The role of various sociodemographic variables in substance abusers, which affected their criminal behavior was also studied. Moreover, in the present study, the personality profile of substance users and nonusers was compared using psychoticism, extraversion, and neuroticism (PEN) inventory. MATERIALS AND METHODS: A total of 50 consecutive subjects diagnosed as per International Classification of Diseases 10 criteria for substance abuse, fulfilling the inclusive and exclusive criteria were taken. A well-matched control was also assessed to compare the studied subject using a well-designed semi-structured proforma and PEN inventory. RESULTS: Most of the substance abusers were Hindus, married, belonged to 21-30 age group and urban domicile, and were presently unemployed, educated up to middle class, and belonged to lower socioeconomic status. Family history of substance use was significant in the subjects, and the chief substance of use was opioids. Scores for psychoticism and neuroticism, as well as the criminal behavior was significantly higher in studied subjects. CONCLUSION: Thus, conclusions drawn were that personality characteristics of the substance abusers differed significantly from the control group and second, the number of variables including occupational status, socioeconomic status, family history of substance use, and type of substance of abuse significantly correlated with the criminal behavior in the substance abusers. Identifying these variables can be the first step in the intervention in substance abusers in order to reduce their future criminal behavior. PMID- 26257482 TI - Personality disorder, emotional intelligence, and locus of control of patients with alcohol dependence. AB - AIM: To assess personality disorder (PD), emotional intelligence (EI), and locus of control of alcohol dependent (AD) patients and its comparison with normal controls. MATERIALS AND METHODS: Based on purposive sampling technique, 33 AD patients were selected from the De-Addiction Ward of Ranchi Institute of Neuro Psychiatry and Allied Sciences (RINPAS) and 33 matched normal subjects were selected from Ranchi and nearby places. Both the groups were matched on various sociodemographic parameters, that is, age, gender, and socioeconomic level. All participants were assessed with Millon Clinical Multiaxial Inventory-III, Mangal EI Inventory, and Locus of Control scale. Obtained responses were scored by using standard scoring procedures and subsequently statistically analyzed by using Chi square test. RESULTS: AD patients have more comorbid pathological personality traits and disorders in comparison to their normal counterparts. Depressive, narcissistic, and paranoid PDs were prominent among AD group; followed by schizotypal, antisocial, negativistic, dependent, schizoid, sadistic, masochistic, and borderline PD. In comparison to normal participants, AD patients were significantly deficient in almost all the areas of EI and their locus of control was externally oriented. CONCLUSION: Patients with AD have significantly higher PDs, low EI, and an external orientation on the locus of control. Identification and management of these comorbid conditions are likely to improve the management and outcome of AD. PMID- 26257483 TI - Cognitive rehabilitation of attention and memory in depression. AB - BACKGROUND: Cognitive deficits are an important component of depression and may remain impaired after recovery from depression. OBJECTIVES: To evaluate the efficacy of cognitive rehabilitation in depression on cognitive dysfunction in the area of attention and memory. MATERIALS AND METHODS: The study was hospital based pre- and post-intervention with follow-up assessment design. Selection of the depressive patients was by purposive sampling. The sample size consists of 30 intervention depressive patients included in the study after giving written informed consent. After preassessment, all patients underwent 15 sessions as part of cognitive rehabilitation. Postassessment was done to see the outcome of cognitive rehabilitation after 3 months follow-up. RESULTS: After the intervention, there was significant improvement in attention and memory area. Along with these deficits, their basic living skills were also improved. CONCLUSION: Cognitive rehabilitation techniques are useful in remediating cognitive dysfunction in the area of attention and memory in patients with depression. PMID- 26257484 TI - The relation between emotional intelligence and criminal behavior: A study among convicted criminals. AB - BACKGROUND: Lack of emotional intelligence (EI) may lead to maladjustment and inability to achieve desired goals. A relationship between low levels of EI and crime has been proposed. AIM: The aim was to assess the relationship between EI and criminal behavior. MATERIALS AND METHODS: Study sample consisted of 202 subjects, in whom 101 subjects were convicted offenders, and 101 were matched normal controls. Offender group comprised of individuals convicted for different crimes such as murder, rape, and robbery, selected from Birsa Munda Central Jail, Hotwar, Ranchi, Jharkhand, India based on purposive sampling. Sample of the normal control group was taken from Ranchi and nearby areas. All subjects gave informed consent for participating in the study. Both the groups were matched on age, gender, education, occupation, and marital status. All participants were assessed on General Health Questionnaire-12 and Mangal Emotional Intelligence Inventory (MEII). The results were analyzed using statistical package SPSS version 20. RESULTS: The group of convicted offenders obtained significantly lower scores on all the domains of MEII such as intrapersonal awareness (own emotions), interpersonal awareness (others emotions), intrapersonal management (own emotions) and interpersonal management (others emotions), and aggregate emotional quotient in comparison to their normal counterparts. CONCLUSION: The convicted offenders group had significantly lower EI compared to normal subjects. Starting EI enhancement program in prison can help the inmates better understand their feelings and emotions. PMID- 26257485 TI - Hazardous alcohol use among doctors in a Tertiary Health Center. AB - BACKGROUND: Doctors have been identified as one of the key agents in the prevention of alcohol-related harm, however, their level of use and attitudes toward alcohol will affect such role. AIM: This study is aimed at describing the pattern of alcohol use and the predictors of hazardous drinking among hospital doctors. SETTING: Study was conducted at the Ekiti State University Teaching Hospital, Ado-Ekiti, Nigeria. DESIGN: A cross-sectional survey involving all the doctors in the teaching hospital. MATERIALS AND METHODS: All the consenting clinicians completed a sociodemographic questionnaire and alcohol use was measured using the 10-item alcohol use disorder identification test (AUDIT) and psychological well-being was measured by the 12-item General Health Questionnaire (GHQ-12). STATISTICAL ANALYSIS USED: Statistical analyses were done using the Statistical Package for Social Sciences version 16. Chi-square tests with Yates correction were used to describe the relationship between respondent's characteristics and AUDIT scores as appropriate. RESULTS: There were a total of 122 participants. Eighty-five (69.7%) of them were abstainers, 28 (23%) were moderate drinkers, and 9 (7.3%) hazardous drinkers. With the exception of age, there was no significant relationship between sociodemographic status, years of practice, specialty of practice, and hazardous alcohol use. Experiencing stress or GHQ score above average is significantly associated with hazardous drinking. CONCLUSION: Hazardous drinking among hospital doctors appears to be essentially a problem of the male gender, especially among those older than 40 years. Stress and other form of psychological distress seem to play a significant role in predicting hazardous drinking among doctors. PMID- 26257486 TI - Gender differences among suicide attempters attending a Crisis Intervention Clinic in South India. AB - BACKGROUND AND OBJECTIVES: Studying gender differences among suicide attempters is important for identifying gender-specific risk factors and for planning management and prevention. Our objective was to delineate gender differences among a well-defined group of suicide attempters. MATERIALS AND METHODS: This record-based study was conducted among patients presenting to a Crisis Intervention Clinic in a Tertiary Care Hospital in South India. Information was gathered regarding sociodemographic and clinical characteristics. Hopelessness was measured using Beck Hopelessness Scale (BHS), and stress was evaluated using Presumptive Stressful Life Events Scale (PSLES). RESULTS: The sample comprised of 162 males and 137 females. Males were significantly older and were more likely to be employed as compared to females. Alcohol use was significantly more in males and number of men who attempted suicide under intoxication was significantly higher. Females had a greater proportion of attempts with the use of plant poisons and medication overdose. There was no significant difference between two genders on BHS though differences were noted on types of stresses reported on PSLES. CONCLUSION: Gender-specific differences were noted with regard to substance use, mode of attempt and types of stressors experienced. Identifying these factors might help us to design targeted interventions to prevent further attempts. PMID- 26257487 TI - Perceived stigma among attendees of psychiatric and nonpsychiatric outpatients department in an industrial township: A comparative study. AB - INTRODUCTION AND CONTEXT: Stigma associated with psychiatric disorders and few somatic disorders such as sexually transmitted diseases (STDs), tuberculosis and leprosy, adversely effects treatment seeking behavior, leads to concealment, and poor compliance with treatment. In busy outpatient departments (OPDs), the issue of stigma is likely to be overlooked. MATERIALS AND METHODS: We carried out a cross-sectional study collecting data on an 8-item stigma scale from patients attending psychiatry and other OPDs of a Tertiary Care Teaching Hospital in an industrial township. Information was collected by face to face interview from 400 patients attending psychiatry OPD and 401 patients attending other OPDs. Validations of the scale were done by face, content, and construct validity. Reliability was appraised by Cronbach's alpha and Guttmann split-half coefficients. Significant differences in answers to the 8-item questionnaire were explored by Chi-square test for individual responses and Kruskal-Wallis test for difference in total stigma score. RESULTS: Patients attending psychiatry OPD consistently gave responses indicating a greater degree of perceived stigma than those attending OPD for somatic disorders. This difference was almost 3-4 times more on most of the items (P < 0.001). Among somatic disorders, stigma was highest (even higher than psychiatric disorders) among STDs, tuberculosis and leprosy patients among these and psychiatric disorders the score was almost 3 times more compared to other somatic disorders (P < 0.001). The scale demonstrated good face, content, and construct validity. Reliability was also very high with Cronbach's alpha coefficient and Guttmann split-half reliability coefficient 0.932 and 0.901 indicating very good internal consistency of the 8 item scale. CONCLUSION: Stigma was higher among STD patients, tuberculosis, leprosy, and psychiatry patients as compared to patients suffering from somatic disorders. Assessment of stigma among these groups of patients can help in planning management and intervention to deal with stigma. This in turn can improve patient compliance. PMID- 26257488 TI - Cavum septum pellucidum in a case of schizophrenia presenting with self mutilating behavior. AB - Cavum septum pellucidum (CSP) is a neurodevelopmental anomaly, which is commonly reported in schizophrenia patients. Various symptoms of schizophrenia, including thought disturbances have been associated with CSP. We present a rare case of undifferentiated schizophrenia with CSP who presented with self-mutilating behaviors. PMID- 26257489 TI - Severe headache as a presenting complaint in sigmoid sinus thrombosis complicated by functional overlay. AB - An otherwise serious and potentially fatal organic condition may present with a co-existing strong functional component. We encountered a female patient who presented with bouts of severe headache over the occipital region, associated with blurring of vision. Initially, non-contrast computed tomography (CT) scan (Brain) showed normal study, and she was deemed as having functional symptoms. Later, magnetic resonance imaging (MRI) (Brain) showed filling defect in right sigmoid sinus and magnetic resonance (MR) venography confirmed right sigmoid sinus thrombosis. On adequate anticoagulation, she did not improve and still had bouts of severe headache, although no longer associated with impaired vision. The treating neurophysician concluded that symptoms could no longer be accounted for by the organic condition. Overt and covert psychosocial stressors were found to be present in a detailed psychological exploration. Psychological intervention effectively controlled the headache. Thus, functional overlay can complicate the clinical picture in a severe organic condition and may require active psychiatric intervention over and above medical treatment. PMID- 26257490 TI - Multiple self-inserted pins and nails in pericardium in a patient of schizophrenia: Case report and review. AB - This report is the case of multiple self-inserted pins and nails in chest and pericardial cavity in a young male suffering from schizophrenia. This act of self mutilation was done to get relief from burning sensation in chest and palpitations. Review of the relevant literature revealed that self-inflicted intra-cardiac needle injuries occur mainly in young and middle-aged adults suffering from psychiatric disorders, commonly depression, schizophrenia, and substance use disorders. In one-fourth of the patients, it is due to deliberate self-harm. About 70% use a single needle but 30% may use multiple needles. Second attempts are rare. Majority of the patients (85%) are managed by surgery and recover from the injury. The condition has a low mortality rate of 5%. PMID- 26257491 TI - Dissociative fugue: Recurrent episodes in a young adult. AB - Dissociative fugue is a rare disorder which has been described as sudden, unexpected, travel away from home or one's customary place of daily activities, with the inability to recall some or all of one's past. There is no systematic data existing on it and very few cases reported in the literature. Here we report a case of fugue in a young adult male who travelled 8 times away from his home during last 11/2 year. He has a loss of memory for episodes with patchy recall of few events. Longest duration of fugue episode was of 1-month. The case describes mode of presentation to hospital and treatment given to restore his identity and reunite him in society and family. PMID- 26257492 TI - Irritable bowel syndrome and its psychological management. AB - Irritable Bowel Syndrome (IBS) is a chronic and disabling gastrointestinal problem that affects psychosocial functioning as well as the quality of life. This case study reports the utility of cognitive behavior therapy as a psychological intervention procedure in a chronic case of IBS. The use of psychological intervention was found to result in a reduction of anxiety; amelioration of the symptoms associated with IBS and improved functioning. PMID- 26257493 TI - Normal pressure hydrocephalus presenting as delusional disorder. AB - Normal pressure hydrocephalus (NPH) is caused by aqueductal stenosis resulting in syndrome of gait disturbance, cognitive impairment, and urinary incontinence. Late onset psychosis should be evaluated thoroughly to rule out any organic cause. We present the case of a female patient presenting with delusions, gait disturbances, urinary incontinence in her 50s. PMID- 26257494 TI - Delusional parasitosis with folie a deux: A case series. AB - Delusional parasitosis (DP) is characterized by single hypochondriacal delusion in which patient feels he/she is infested with insects. The authors present a case series of three cases of DP with shared psychotic disorder (folie a deux) in which one individual developed a delusional belief in the context of a close relationship with another person or people who already had an established delusional idea. All patients of DP were assessed in the outpatient department of Psychiatry of a tertiary care hospital. Diagnosis of DP was made on detail clinical history and supporting clinical findings. All our primary cases had DP and the accompanying relatives of our patients had folie a deux as they shared the belief of parasite infestation which was firm and persisted despite evidence to the contrary. The primary cases of delusional parasitosis responded well to oral risperidone. The intensity of the belief in the secondary person also reduced with improvement in the symptoms of the patients. PMID- 26257495 TI - Neuropsychological functioning in Wernicke's encephalopathy. AB - CONTEXT: Wernicke's encephalopathy (WE) is caused by thiamine (Vitamin B1) deficiency and most commonly found in chronic alcoholism and malnutrition. Clinically, the key features are mental status disturbances (global confusion), oculomotor abnormalities, and gait disturbances (ataxia). Apart from these clinical features, we can find deficits in neuropsychological functioning in patients with WE, which is more prominent after the improvement in the physical conditions. Neuropsychological functioning includes both basic cognitive processes (i.e., attention-concentration) as well as higher order cognitive processes (i.e., memory, executive functioning, reasoning), which is much vital for the maintenance of quality of life of an individual. However, unfortunately, in most of the cases, neuropsychological functioning is ignored by the clinicians. MATERIALS AND METHODS: In this study four case reports of WE have been presented. The patients were taken from the outdoor department of Mental Health Institute, S.C.B. Medical College, Cuttack, Odisha. Neuropsychological functioning was measured by administration of PGIBBD and Quality of Life was measured by WHO-QOL BREF Odia Version. DISCUSSION: As described in the literature, among the three cardinal signs (global confusion, ataxia, and ocular sings), the first two were present in all cases, but nystagmus was present in only two cases. Memory dysfunction was so disabling that the persons were unable to maintain a good Quality of Life and occupational impairment was prominent. There are disturbances in recent, remote memory, immediate recall, delayed recall, and attention and concentration, ultimately creating both physical and mental disability. PGI-BBD findings also suggest the overall impairment in neuropsychological functioning other than memory, that is, executive functioning, visual acuity, and depth perception. Findings of WHO-QOL BREF suggest the impairment of four domains of QOL in all the cases, but the severity level varies from person to person. CONCLUSION: Like the three cardinal features, neuropsychological dysfunction in WE should be given importance, which is a most vital component for the maintenance of QOL. As a result, the disability produced by this condition can be well managed. PMID- 26257496 TI - Undergraduate psychiatry education in India: Where do we stand on the crossroads? PMID- 26257497 TI - Peacekeeping operations: Challenges ahead. PMID- 26257501 TI - Fish remains as a source to reconstruct long-term changes of fish communities in the Austrian and Hungarian Danube. AB - The main objective of this paper is to investigate how archaeological fish remains and written historical records can contribute to the reconstruction of long-term developments of fish communities along the Austrian and Hungarian Danube. Although such approaches are sensitive to various factors, the chronological subdivision and relative quantification of proxy data demonstrate environmental and faunal changes from Prehistory onwards. Intensification of fisheries, decline of large specimens and massive exploitation of small and young fish point to increasing pressure along the chronological sequence towards Early Modern times. One result of this impact was the establishment of regulations and laws to protect such fish. At the same time, the rise of aquaculture and common carp cultivation can be viewed as another upshot of human impact on the Danube's environment. Finally, the massive import of salted marine fish reflects a compensation for the undersupply caused by overexploitation of the Danube fish fauna and points to the growing demand for fish as food in late medieval and Early Modern times. PMID- 26257502 TI - Historical change in fish species distribution: shifting reference conditions and global warming effects. AB - Species distributions models (SDM) that rely on estimated relationships between present environmental conditions and species presence-absence are widely used to forecast changes of species distributions caused by global warming but far less to reconstruct historical assemblages. By compiling historical fish data from the turn to the middle of the twentieth century in a similar way for several European catchments (Rhone, Danube), and using already published SDMs based on current observations, we: (1) tested the predictive accuracy of such models for past climatic conditions, (2) compared observed and expected cumulated historical species occurrences at sub-catchment level, and (3) compared the annual variability in the predictions within one sub-catchment (Salzach) under a future climate scenario to the long-term variability of occurrences reconstructed during an extended historical period (1800-2000). We finally discuss the potential of these SDMs to define a "reference condition", the possibility of a shift in baseline condition in relation with anthropogenic pressures, and past and future climate variability. The results of this study clearly highlight the potential of SDM to reconstruct the past composition of European fish assemblages and to analyze the historical ecological status of European rivers. Assessing the uncertainty associated with species distribution projections is of primary importance before evaluating and comparing the past and future distribution of species within a given catchment. PMID- 26257503 TI - STANDARDIZATION AND THE GROUP LASSO PENALTY. AB - We re-examine the original Group Lasso paper of Yuan and Lin (2007). The form of penalty in that paper seems to be designed for problems with uncorrelated features, but the statistical community has adopted it for general problems with correlated features. We show that for this general situation, a Group Lasso with a different choice of penalty matrix is generally more effective. We give insight into this formulation and show that it is intimately related to the uniformly most powerful invariant test for inclusion of a group. We demonstrate the efficacy of this method- the "standardized Group Lasso"- over the usual group lasso on real and simulated data sets. We also extend this to the Ridged Group Lasso to provide within group regularization as needed. We discuss a simple algorithm based on group-wise coordinate descent to fit both this standardized Group Lasso and Ridged Group Lasso. PMID- 26257504 TI - Penalized Q-Learning for Dynamic Treatment Regimens. AB - A dynamic treatment regimen incorporates both accrued information and long-term effects of treatment from specially designed clinical trials. As these trials become more and more popular in conjunction with longitudinal data from clinical studies, the development of statistical inference for optimal dynamic treatment regimens is a high priority. In this paper, we propose a new machine learning framework called penalized Q-learning, under which valid statistical inference is established. We also propose a new statistical procedure: individual selection and corresponding methods for incorporating individual selection within penalized Q-learning. Extensive numerical studies are presented which compare the proposed methods with existing methods, under a variety of scenarios, and demonstrate that the proposed approach is both inferentially and computationally superior. It is illustrated with a depression clinical trial study. PMID- 26257505 TI - Sensemaking Strategies for Ethical Decision-making. AB - The current study uses a sensemaking model and thinking strategies identified in earlier research to examine ethical decision-making. Using a sample of 163 undergraduates, a low fidelity simulation approach is used to study the effects personal involvement (in causing the problem and personal involvement in experiencing the outcomes of the problem) could have on the use of cognitive reasoning strategies that have been shown to promote ethical decision-making. A mediated model is presented which suggests that environmental factors influence reasoning strategies, reasoning strategies influence sensemaking, and sensemaking in turn influences ethical decision-making. Findings were mixed but generally supported the hypothesized model. Interestingly, framing the outcomes of ethically charged situations in terms of more global organizational outcomes rather than personal outcomes was found to promote the use of pro-ethical cognitive reasoning strategies. PMID- 26257506 TI - Applying Cases to Solve Ethical Problems: The Significance of Positive and Process-Oriented Reflection. AB - This study examined the role of reflection on personal cases for making ethical decisions with regard to new ethical problems. Participants assumed the position of a business manager in a hypothetical organization and solved ethical problems that might be encountered. Prior to making a decision for the business problems, participants reflected on a relevant ethical experience. The findings revealed that application of material garnered from reflection on a personal experience was associated with decisions of higher ethicality. However, whether the case was viewed as positive or negative, and whether the outcomes, process, or outcomes and processes embedded in the experience were examined, influenced the application of case material to the new problem. As expected, examining positive experiences and the processes involved in those positive experiences resulted in greater application of case material to new problems. Future directions and implications for understanding ethical decision-making are discussed. PMID- 26257507 TI - A Qualitative Assessment of the Parenting Challenges and Treatment Needs of Mothers with Borderline Personality Disorder. AB - There are currently no empirically supported interventions to target parenting among mothers who have Borderline Personality Disorder (BPD). The current study uses Consensus Qualitative Research (CQR) methodology to: I) learn about mothers' experiences of parenting with BPD, and II) identify treatment modifications to Dialectical Behavior Therapy (DBT) as suggested by mothers with BPD who are currently engaged in DBT skills training. Twenty-three mothers were recruited from intensive outpatient and partial hospitalization programs that teach DBT skills. A total of 9 focus groups that met one time were conducted asking women a series of questions regarding their experiences of parenting with BPD and how they would modify DBT to address parenting issues. Using the CQR approach, we coded domains and categories that were discussed by mothers in the focus groups. Coding revealed that mothers with BPD wished parenting was integrated more in their current DBT skills groups. In addition, one of the most prominent themes to emerge was that parenting is particularly stressful to mothers with BPD and is associated with guilt, uncertainty, and worry. Finally, mothers offered many ideas for how to integrate parenting-focused interventions into DBT. The CQR method revealed gaps in current treatment for mothers with BPD and provided useful ideas for how to modify DBT to target parenting and integrate these modifications into other approaches for treating mothers with BPD. PMID- 26257508 TI - Monitoring Client Progress and Feedback in School-Based Mental Health. AB - Research in children's mental health has suggested that emotional and behavioral problems in are inextricably tied to academic difficulties. However, evidence based programs implemented in school-based mental health tend to focus primarily on treatment practices, with less explicit emphasis on components of evidence based assessment (EBA), such as progress monitoring and feedback. The current paper describes two studies that incorporated standardized assessment and progress monitoring/feedback into school-based mental health programs. Barriers to implementation are identified, recommendations for clinicians implementing EBA in the school setting are provided, and examples of mental health and academic indicators are discussed. PMID- 26257509 TI - Noninvasive intraocular pressure monitoring: current insights. AB - Glaucoma is the second leading cause of blindness worldwide and intraocular pressure (IOP) is currently its only modifiable risk factor. Peak IOP has for a long time been considered as a major contributor to glaucoma progression, but its effects may depend not only on its magnitude, but also on its time course. The IOP is nowadays considered to be a dynamic parameter with a circadian rhythm and spontaneous changes. The current practice of punctual measuring the IOP during office hours is therefore a suboptimal approach, which does not take into account the natural fluctuation of IOP. Because of its static nature a single IOP measurement in sitting position fails to document the true range of an individual's IOP, peak IOP, or variation throughout the day. Phasing means monitoring a patient's IOP during the daytime or over a 24-hour period. This can provide additional information in the management of glaucoma patients. This review focuses on the current insight of non-invasive IOP monitoring as a method of obtaining more complete IOP profiles. Invasive techniques using an implantable sensor are beyond the scope of this review. PMID- 26257510 TI - Peripapillary choroidal thickness in healthy Turkish subjects. AB - AIM: The objective of the study reported here was to investigate the normal peripapillary choroidal thickness (CT), measured by enhanced depth imaging optical coherence tomography (EDI-OCT), in healthy Turkish volunteers. MATERIALS AND METHODS: In this prospective cross-sectional study, 57 eyes of 57 healthy Turkish subjects were enrolled. Each participant underwent a comprehensive ophthalmic examination and peripapillary CT measurement using EDI-OCT. RESULTS: The mean age of the 25 female and 32 male patients in the study was 30.9+/-10.6 years (range, 18-56 years). The mean peripapillary CT at the superior, inferior, nasal, and temporal sites was 225+/-57, 183+/-47, 220+/-57, and 233+/-59 MUm, respectively. The inferior peripapillary CT value was significantly lower than the peripapillary CT values (P<0.001 for all), whereas no significant differences were found between the superior, nasal, and temporal peripapillary CT values. CONCLUSION: The findings of the study revealed that Turkish people had significantly lower peripapillary CT values in the inferior quadrant than in the superior, nasal, and temporal quadrants. PMID- 26257511 TI - Comparison of the pharmacokinetics and tolerability of HCP1004 (a fixed-dose combination of naproxen and esomeprazole strontium) and VIMOVO(r) (a marketed fixed-dose combination of naproxen and esomeprazole magnesium) in healthy volunteers. AB - BACKGROUND: HCP1004 is a newly developed fixed-dose combination of naproxen (500 mg) and esomeprazole strontium (20 mg) that is used in the treatment of rheumatic diseases and can reduce the risk of nonsteroidal anti-inflammatory drug associated ulcers. The aim of this study was to evaluate the pharmacokinetics (PK) and safety of HCP1004 compared to VIMOVO((r)) (a marketed fixed-dose combination of naproxen and esomeprazole magnesium). SUBJECTS AND METHODS: An open-label, randomized, two-treatment, two-sequence crossover, single-dose clinical study was conducted in 70 healthy volunteers. In each period, a reference (VIMOVO((r))) or test (HCP1004) drug was administered orally, and serial blood samples for PK analysis were collected up to 72 hours after dosing. To evaluate the PK profiles, the maximum plasma concentration (Cmax) and the area under the concentration-time curve from 0 to the last measurable time (AUC0-t) were estimated using a noncompartmental method. Safety profiles were evaluated throughout the study. RESULTS: Sixty-six of the 70 subjects completed the study. The Cmax (mean +/- standard deviation) and AUC0-t (mean +/- standard deviation) for naproxen in HCP1004 were 61.67 +/- 15.16 ug/mL and 1,206.52 +/- 166.46 h . ug/mL, respectively; in VIMOVO((r)); these values were 61.85 +/- 14.54 ug/mL and 1,211.44 +/- 170.01 h . ug/mL, respectively. The Cmax and AUC0-t for esomeprazole in HCP1004 were 658.21 +/- 510.91 ng/mL and 1,109.11 +/- 1,111.59 h . ng/mL, respectively; for VIMOVO((r)), these values were 595.09 +/- 364.23 ng/mL and 1,015.12 +/- 952.98 h . ng/mL, respectively. The geometric mean ratios and 90% confidence intervals (CIs) (HCP1004 to VIMOVO((r))) of the Cmax and AUC0-t of naproxen were 0.99 (0.94-1.06) and 1.00 (0.98-1.01), respectively. For esomeprazole, the geometric mean ratios (90% CI) for the Cmax and AUC0-t were 0.99 (0.82-1.18) and 1.04 (0.91-1.18), respectively. The overall results of the safety assessment showed no clinically significant issues for either treatment. CONCLUSION: The PK of HCP1004 500/20 mg was comparable to that of VIMOVO((r)) 500/20 mg for both naproxen and esomeprazole after a single oral dose. Both drugs were well-tolerated without any safety issues. PMID- 26257514 TI - Supporting self-management of type 2 diabetes: is there a role for the community pharmacist? AB - BACKGROUND: Evidence supports the efficacy of pharmacy services in type 2 diabetes (T2D). However, little is known about consumer perspectives on the role of community pharmacists in diabetes care. The objectives of this study were to identify potential unmet needs and explore preferences for pharmacist-delivered support for T2D. METHODS: A qualitative study using focus groups was conducted in Sydney, Australia. Patients with T2D who were members of the Australian Diabetes Council in Sydney, Australia, were recruited through a survey on medication use in T2D. Five focus groups with a total of 32 consumers with T2D were recorded, transcribed, and thematically analyzed. RESULTS: The key themes were 1) the experiences of diabetes services received, 2) the potential to deliver self management services, and 3) the suggested role of pharmacist in supporting diabetes management. Gaps in understanding and some degree of nonadherence to self-management signaled a potential for self-management support delivered by pharmacists. However, consumers still perceive that the main role of pharmacists in diabetes care centers on drug management services, with some enhancements to support adherence and continuity of supply. Barriers to diabetes care services included time constraints and a perceived lack of interest by pharmacists. CONCLUSION: Given the unmet needs in diabetes self-management, opportunities exist for pharmacists to be involved in diabetes care. The challenge is for pharmacists to upgrade their diabetes knowledge and skills, organize their workflow, and become proactive in delivering diabetes care support. PMID- 26257512 TI - Understanding the cross-resistance of oseltamivir to H1N1 and H5N1 influenza A neuraminidase mutations using multidimensional computational analyses. AB - This study embarks on a comprehensive description of the conformational contributions to resistance of neuraminidase (N1) in H1N1 and H5N1 to oseltamivir, using comparative multiple molecular dynamic simulations. The available data with regard to elucidation of the mechanism of resistance as a result of mutations in H1N1 and H5N1 neuraminidases is not well established. Enhanced post-dynamic analysis, such as principal component analysis, solvent accessible surface area, free binding energy calculations, and radius of gyration were performed to gain a precise insight into the binding mode and origin of resistance of oseltamivir in H1N1 and H5N1 mutants. Three significant features reflecting resistance in the presence of mutations H274Y and I222K, of the protein complexed with the inhibitor are: reduced flexibility of the alpha-carbon backbone; an improved DeltaEele of ~15 (kcal/mol) for H1N1 coupled with an increase in DeltaGsol (~13 kcal/mol) from wild-type to mutation; a low binding affinity in comparison with the wild-type of ~2 (kcal/mol) and ~7 (kcal/mol) with respect to each mutation for the H5N1 systems; and reduced hydrophobicity of the overall surface structure due to an impaired hydrogen bonding network. We believe the results of this study will ultimately provide a useful insight into the structural landscape of neuraminidase-associated binding of oseltamivir. Furthermore, the results can be used in the design and development of potent inhibitors of neuraminidases. PMID- 26257513 TI - CTGF siRNA ameliorates tubular cell apoptosis and tubulointerstitial fibrosis in obstructed mouse kidneys in a Sirt1-independent manner. AB - Transforming growth factor-beta1 (TGF-beta1) plays an important role in the pathogenesis and progression of chronic kidney disease. Connective tissue growth factor (CTGF) is a critical fibrogenic mediator of TGF-beta1. Mammalian sirtuin 1 (Sirt1) is reported to attenuate renal fibrosis by inhibiting the TGF-beta1 pathway. This study was designed to detect whether the delivery of CTGF siRNA in vivo directly ameliorates renal fibrosis. Furthermore, the relationship with Sirt1 underlying the protective effect of CTGF siRNA on interstitial fibrosis and apoptosis was explored. Here, we report that the expressions of CTGF and TGF beta1 were increased while Sirt1 expression and activity were both dramatically decreased in mouse kidneys with unilateral ureteral obstruction. Recombinant human TGF-beta1 treatment in HK-2 cells increased CTGF levels and remarkably decreased Sirt1 levels and was accompanied by apoptosis and release of fibrosis related factors. Recombinant human CTGF stimulation also directly induced apoptosis and fibrosis. The CTGF siRNA plasmid ameliorated tubular cell apoptosis and tubulointerstitial fibrosis, but did not affect Sirt1 expression and activity both in vivo and in vitro. Furthermore, overexpression of Sirt1 abolished TGF beta1-induced cell apoptosis and fibrosis, while Sirt1 overexpression suppressed CTGF expression via stimulation by TGF-beta1. This study provides evidence that treatment strategies involving the delivery of siRNA targeting potentially therapeutic transgenes may be efficacious. Our results suggest that the decrease in Sirt1 is associated with the upregulated expression of CTGF in renal fibrosis, and may aid in the design of new therapies for the prevention of renal fibrosis. PMID- 26257515 TI - Development and evaluation of the Measure of Drug Self-Management. AB - BACKGROUND: Current adherence scales often fail to assess the full spectrum of behaviors associated with safe and appropriate drug use and may be unsuitable for patients with limited health literacy. We sought to develop and evaluate a comprehensive yet brief Measure of Drug Self-Management (MeDS) for use in research and clinical settings among diverse patient groups. METHODS: Expert opinion, literature reviews, and interviews with patients and providers were utilized to create and revise potential items. Item performance testing was then conducted among 193 adult English-speaking patients with hypertension and diabetes. Factor analysis was used to inform item selection. Reliability was assessed via calculations of internal consistency. To assess construct and predictive validity, MeDS scores were compared with scores from the 8-item Morisky Medication Adherence Scale and relevant clinical measures (HbA1c, blood pressure, and low-density lipoprotein cholesterol). RESULTS: The MeDS demonstrated adequate internal consistency with a Cronbach's alpha of 0.72. The MeDS was significantly correlated with the Morisky Medication Adherence Scale (r= -0.62; P<0.001). The MeDS was also associated with clinical measures, with statistically significant correlations found between MeDS scores and low-density lipoprotein cholesterol (r= -0.27, P<=0.001) and diastolic blood pressure (r= 0.18, P=0.01). CONCLUSION: The MeDS seems to be a valid and reliable tool that can be used to assess medication self-management skills among diverse patients, including those with limited literacy skills. Future studies are needed to test the tool in actual use and explore clinical applications. PMID- 26257516 TI - Light-chain cardiac amyloidosis with neuropathy: a case report. AB - Light-chain amyloidosis is a relatively rare multisystem disorder. The disease often is normally difficult to diagnose due to its broad range of characters without specific symptoms. A 62-year-old male patient presented with heart failure after experiencing a long period of unexplained and untreated gastrointestinal symptoms. Clinical examination and laboratory findings indicated a systemic process with cardiac involvement. Echocardiography revealed concentric left ventricular hypertrophy with enhanced echogenicity and preserved ejection fraction. Rectum biopsy confirmed amyloid deposition. The side effect of delayed diagnosis on prognosis and the appropriate diagnostic strategy has been discussed. PMID- 26257517 TI - Prevalence of chronic obstructive pulmonary disease among patients with systemic arterial hypertension without respiratory symptoms. AB - BACKGROUND: The diagnosis of chronic obstructive pulmonary disease (COPD) is often delayed until later stages of the disease. The purpose of the present study was to determine the prevalence of COPD among adults on treatment for systemic arterial hypertension independently of the presence of respiratory symptoms. METHODS: This cross-sectional study included adults aged >=40 years with tobacco/occupational exposure and systemic arterial hypertension diagnosed at three Primary Health Care facilities in Goiania, Brazil. Patients were evaluated using a standardized respiratory questionnaire and spirometry. COPD prevalence was measured considering the value of forced vital capacity and/or forced expiratory volume in 1 second <0.70. RESULTS: Of a total of 570 subjects, 316 (55%) met inclusion criteria and were invited to participate. Two hundred and thirty-three (73.7%) patients with arterial hypertension reported at least one respiratory symptom, while 83 (26.3%) reported no respiratory symptoms; 41 (17.6%) patients with arterial hypertension and at least one respiratory symptom, and 10 (12%) patients with arterial hypertension but no respiratory symptoms were diagnosed with COPD (P=0.24). The prevalence of COPD in people with no previous COPD diagnosis was greater among those with no respiratory symptoms (100%) than among those with respiratory symptoms (56.1%) (P=0.01). CONCLUSION: Our findings suggest that regardless of the presence of respiratory symptoms, individuals aged >=40 years with tobacco/occupational exposure and arterial hypertension may benefit from spirometric evaluation. PMID- 26257518 TI - Construction and characterization of an anti-CD20 mAb nanocomb with exceptionally excellent lymphoma-suppressing activity. AB - The CD20-directed monoclonal antibody rituximab (RTX) established a new era in the treatment of non-Hodgkin lymphoma (NHL); however, suboptimal response and/or resistance to RTX still limit its clinical merits. Although four effector mechanisms are validated to participate in CD20-based immunotherapy, including complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, caspase-dependent apoptosis, and lysosome-mediated programmed cell death (PCD), they could hardly be synchronously activated by any anti-CD20 mAb or mAb derivative until now. Herein, a novel mAb nanocomb (polyethylenimine polymer-RTX tositumomab [PPRT nanocomb]) was firstly constructed through mass arming two different anti-CD20 mAbs (RTX and tositumomab) to one polymer by nanotechnology. Comparing with free mAbs, PPRT nanocomb possesses a comparable binding ability and reduced "off-rate" to surface CD20 of NHL cells. When treated by PPRT nanocomb, the caspase-dependent apoptosis was remarkably enhanced except for concurrently eliciting complement-dependent cytotoxicity, antibody-dependent cell mediated cytotoxicity, and lysosome-mediated PCD. Besides, "cross-cell link" assisted homotypic adhesion by PPRT nanocomb further enhanced the susceptibility to PCD of lymphoma cells. Pharmacokinetic assays revealed that PPRT nanocomb experienced a relatively reduced clearance from peripheral blood compared with free antibodies. With the cooperation of all the abovementioned superiorities, PPRT nanocomb exhibits exceptionally excellent in vivo antitumor activities in both disseminated and localized human NHL xenotransplant models. PMID- 26257519 TI - A curcumin-loaded liquid crystal precursor mucoadhesive system for the treatment of vaginal candidiasis. AB - Women often develop vaginal infections that are caused primarily by organisms of the genus Candida. The current treatments of vaginal candidiasis usually involve azole-based antifungals, though fungal resistance to these compounds has become prevalent. Therefore, much attention has been given to molecules with antifungal properties from natural sources, such as curcumin (CUR). However, CUR has poor solubility in aqueous solvents and poor oral bioavailability. This study attempted to overcome this problem by developing, characterizing, and evaluating the in vitro antifungal action of a CUR-loaded liquid crystal precursor mucoadhesive system (LCPM) for vaginal administration. A low-viscosity LCPM (F) consisting of 40% wt/wt polyoxpropylene-(5)-polyoxyethylene-(20)-cetyl alcohol, 50% wt/wt oleic acid, and 10% wt/wt chitosan dispersion at 0.5% with the addition of 16% poloxamer 407 was developed to take advantage of the lyotropic phase behavior of this formulation. Notably, F could transform into liquid crystal systems when diluted with artificial vaginal mucus at ratios of 1:3 and 1:1 (wt/wt), resulting in the formation of F30 and F100, respectively. Polarized light microscopy and rheological studies revealed that F behaved like an isotropic formulation, whereas F30 and F100 behaved like an anisotropic liquid crystalline system (LCS). Moreover, F30 and F100 presented higher mucoadhesion to porcine vaginal mucosa than F. The analysis of the in vitro activity against Candida albicans revealed that CUR-loaded F was more potent against standard and clinical strains compared with a CUR solution. Therefore, the vaginal administration of CUR-loaded LCPMs represents a promising platform for the treatment of vaginal candidiasis. PMID- 26257520 TI - Ongoing ethical issues concerning authorship in biomedical journals: an integrative review. AB - Health professionals publishing within the field of health sciences continue to experience issues concerning appropriate authorship, which have clinical, ethical, and academic implications. This integrative review sought to explore the key issues concerning authorship from a bioethical standpoint, aiming to explore the key features of the authorship debate. Studies were identified through an electronic search, using the PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Scopus databases of peer-reviewed research, published between 2009 and 2014, limited to English language research, with search terms developed to reflect the current issues of authorship. From among the 279 papers identified, 20 research papers met the inclusion criteria. Findings were compiled and then arranged to identify themes and relationships. The review incorporated a wide range of authorship issues encompassing equal credited authors, honorary (guest/gift) and ghost authorship, perception/experiences of authorship, and guidelines/policies. This review suggests that the International Committee of Medical Journal Editors' (ICMJE) recommended guidelines for authorship are not reflected in current authorship practices within the domain of health sciences in both low-and high-impact-factor journals. This devaluing of the true importance of authorship has the potential to affect the validity of authorship, diminish the real contributions of the true authors, and negatively affect patient care. PMID- 26257521 TI - Numerical optimization of targeted delivery of charged nanoparticles to the ostiomeatal complex for treatment of rhinosinusitis. AB - BACKGROUND: Despite the prevalence of rhinosinusitis that affects 10%-15% of the population, current inhalation therapy shows limited efficacy. Standard devices deliver <5% of the drugs to the sinuses due to the complexity of nose structure, secluded location of the sinus, poor ventilation, and lack of control of particle motions inside the nasal cavity. METHODS: An electric-guided delivery system was developed to guide charged particles to the ostiomeatal complex (OMC). Its performance was numerically assessed in an MRI-based nose-sinus model. Key design variables related to the delivery device, drug particles, and patient breathing were determined using sensitivity analysis. A two-stage optimization of design variables was conducted to obtain the best performance of the delivery system using the Nelder-Mead algorithm. RESULTS AND DISCUSSION: The OMC delivery system exhibited high sensitivity to the applied electric field and electrostatic charges carried by the particles. Through the synthesis of electric guidance and point drug release, the new delivery system eliminated particle deposition in the nasal valve and turbinate regions and significantly enhanced the OMC doses. An OMC delivery efficiency of 72.4% was obtained with the optimized design, which is one order of magnitude higher than the standard nasal devices. Moreover, optimization is imperative to achieve a sound delivery protocol because of the large number of design variables. The OMC dose increased from 45.0% in the baseline model to 72.4% in the optimized system. The optimization framework developed in this study can be easily adapted for the delivery of drugs to other sites in the nose such as the ethmoid sinus and olfactory region. PMID- 26257522 TI - Dual-functional c(RGDyK)-decorated Pluronic micelles designed for antiangiogenesis and the treatment of drug-resistant tumor. AB - Dual-functional drug delivery system was developed by decorating c(RGDyK) (cyclic RGD [arginine-glycine-aspartic acid] peptide) with Pluronic polymeric micelles (c[RGDyK]-FP-DP) to overcome the drawbacks of low transport of chemotherapeutics across the blood-tumor barrier and poor multidrug-resistant (MDR) tumor therapy. c(RGDyK) that can bind to the integrin protein richly expressed at the site of tumor vascular endothelial cells and tumor cells with high affinity and specificity was conjugated to the N-hydroxysuccinimide-activated PEO terminus of the Pluronic F127 block copolymer. In this study, decreased tumor angiogenic and increased apoptotic activity in MDR cancer cells were observed after the treatment with c(RGDyK)-FP-DP. c(RGDyK)-FP-DP was fully characterized in terms of morphology, particle size, zeta potential, and drug release. Importantly, in vitro antiangiogenesis results demonstrated that c(RGDyK)-FP-DP had a significant inhibition effect on the tubular formation of human umbilical vein endothelial cells and promoted cellular apoptotic activity in MDR KBv cells. In addition, the growth inhibition efficacy of KBv tumor spheroids after crossing the blood-tumor barrier was obviously increased by c(RGDyK)-FP-DP compared to other control groups. Results suggested that c(RGDyK)-decorated Pluronic polymeric micelles can take pharmacological action on both human umbilical vein endothelial cells and KBv MDR cancer cells, resulting in a dual-functional anticancer effect similar to that observed in our in vitro cellular studies. PMID- 26257523 TI - Association between toll-like receptor 4 expression and symptoms of major depressive disorder. AB - BACKGROUND: In our previous study, toll-like receptor 4 (TLR4) mRNA expression level was associated with severity of major depressive disorder (MDD) evaluated with the 17-item Hamilton Depression Rating Scale (HAMD-17). However, there are few studies that have investigated the relationship between symptoms of MDD and changes in TLR4 expression. Therefore, the aim of the present study was to further analyze the association between subscales of HAMD-17 and TLR4. METHODS: Fifty-one patients with MDD (15 male and 36 female) participated in this study. HAMD-17 was used to assess the symptoms of major depression. The mRNA expression levels of TLR4 were examined in parallel with a housekeeping gene, using real time polymerase chain reaction. A stepwise linear regression forward model was used to evaluate the relationships between items of HAMD-17 and TLR4 expression. RESULTS: Some sickness behavior-associated symptoms, including suicide, somatic symptoms of anxiety, or performance of work and activities, were not associated with TLR4 expression. However, psychological signs of anxiety and loss of weight in HAMD-17 can predict the expression level of TLR4. CONCLUSION: Our results suggest a significant association between anxiety, body weight loss, and TLR4 mRNA levels in patients with MDD. Larger longitudinal studies combining both subjective and objective measures of depression are needed to clarify the link between TLR4 and symptoms of depression. PMID- 26257525 TI - Determination and validation of mTOR kinase-domain 3D structure by homology modeling. AB - The AKT/mammalian target of rapamycin (mTOR) pathway is considered as one of the commonly activated and deregulated signaling pathways in human cancer. mTOR is associated with other proteins in two molecular complexes: mTOR complex 1/Raptor and the mTOR complex 2/Rictor. Using the crystal structure of the related lipid kinase PI3Kgamma, we built a model of the catalytic region of mTOR. The modeling of the three-dimensional (3D) structure of the mTOR was performed by homology modeling program SWISS-MODEL. The quality and validation of the obtained model were performed using PROCHECK and PROVE softwares. The overall stereochemical property of the protein was assessed by the Ramachandran plot. The model validation was also done by docking of known inhibitors. In this paper, we describe and validate a 3D model for the mTOR catalytic site. PMID- 26257526 TI - The role of (18)F-FDG PET/CT imaging in patient with malignant PEComa treated with mTOR inhibitor. AB - Malignant perivascular epithelioid cell tumor (malignant PEComa) is a rare disease for which the diagnostic criteria and treatment options have not been established. Since PEComa is associated with upregulation of mammalian target of rapamycin (mTOR) pathway which controls Glut-1 (glucose transporter) function, increased (18)F-fluorodeoxyglucose ((18)F-FDG) uptake may indicate the over activation of mTOR pathway and may guide selectively inhibiting mTOR pathway treatment. We report a malignant PEComa patient who presented for (18)F-FDG positron emission tomography/computed tomography (PET/CT) restaging. The tumor had shown significant avidity on PET/CT as well as an evident response to sirolimus (rapamycin, RapamuneTM) that supports the utility of mTOR inhibitors as an effective treatment for malignant PEComa. Therefore, (18)F-FDG PET/CT is helpful in restaging and guiding treatment for malignant PEComa with mTOR inhibitors. PMID- 26257527 TI - A comparison of MRI tissue relaxometry and ROI methods used to determine regional brain iron concentrations in restless legs syndrome. AB - PURPOSE: Magnetic resonance imaging relaxometry studies differed on the relaxometry methods and their approaches to determining the regions of interest (ROIs) in restless legs syndrome (RLS) patients. These differences could account for the variable and inconsistent results found across these studies. The aim of this study was to assess the relationship between the different relaxometry methods and different ROI approaches using each of these methods on a single population of controls and RLS subjects. METHODS: A 3.0-T magnetic resonance imaging with the gradient-echo sampling of free induction decay and echo pulse sequence was used. The regional brain "iron concentrations" were determined using three relaxometry metrics (R2, R2*, and R2') through two different ROI methods. The substantia nigra (SN) was the primary ROI with red nucleus, caudate, putamen, and globus pallidus as the secondary ROIs. RESULTS: Thirty-seven RLS patients and 40 controls were enrolled. The iron concentration as determined by R2 did not correlate with either of the other two methods, while R2* and R2' showed strong correlations, particularly for the substantia nigra and red nucleus. In the fixed shape ROI method, the RLS group showed a lower iron index compared to the control group in the substantia nigra and several other regions. With the semi-automated ROI method, however, only the red nucleus showed a significant difference between the two groups. CONCLUSION: Both the relaxometry and ROI determination methods significantly influenced the outcome of studies that used these methods to estimate regional brain iron concentrations. PMID- 26257528 TI - Observational longitudinal study of symptom burden and time for recovery from community-acquired pneumonia reported by older adults surveyed nationwide using the CAP Burden of Illness Questionnaire. AB - BACKGROUND: Millions of older adults who develop community-acquired pneumonia (CAP) each year survive, but there is a large knowledge gap on the burden of CAP and the recovery process in survivors from the patient perspective. METHODS: The newly developed CAP Burden of Illness Questionnaire was administered through a Web survey to a nationwide sample of US adults aged >=50 years who were recently diagnosed with CAP. Survey respondents with unresolved symptoms or other CAP related health problems completed a second survey 30 days later; a third survey was completed another 30 days later by respondents with unresolved symptoms or problems. Nationally representative results describing the average time to recovery of symptoms and other CAP-related problems were achieved using post stratification weights. RESULTS: Five hundred participants completed the initial survey. The time to resolution for the CAP symptoms of weakness, shortness of breath, and tiredness exceeded 3 weeks on average. There was an average of 13 days of absenteeism, and 3 weeks (mean =21 days) before achieving full work/activity productivity after CAP. For participants with health conditions that worsened from pneumonia, chronic emphysema and chronic obstructive pulmonary disease took the longest to return to baseline (mean =60 and 52.4 days, respectively). CONCLUSION: The results from this study demonstrate that older adults surviving a CAP episode experience a significant multi-symptom illness with long recovery periods to achieve pre-CAP health and productivity. These findings highlight the need for further research on effective clinician-patient communication, the need for patient-centered outcomes in clinical trials for CAP therapeutics, adequate home care during the recovery process, and the pursuit of CAP prevention strategies. PMID- 26257529 TI - Is it fair for a junior doctor's deanery to be largely based on one test: a student's perspective. AB - The manner in which UK medical students are allocated foundation jobs is a controversial system. As medical students in the UK, we are subject to this system and have found students and junior doctors have varying opinions on it. Ultimately this led us to question, is this is a fair system? PMID- 26257524 TI - Bridging the gap between education and appropriate use of benzodiazepines in psychiatric clinical practice. AB - More than half a century after their discovery, benzodiazepines (BDZs) still represent one of the largest and most widely prescribed groups of psychotropic compounds, not only in clinical psychiatry but also in the entire medical field. Over the last two decades, however, there has been an increased focus on the development of antidepressants and antipsychotics on the part of the pharmaceutical industry, clinicians, and researchers, with a reduced interest in BDZs, in spite of their widespread clinical use. As a consequence, many psychiatric residents, medical students, nurses, and other mental health professionals might receive poor academic teaching and training regarding these agents, and have the false impression that BDZs represent an outdated chapter in clinical psychopharmacology. However, recent advances in the field, including findings concerning epidemiology, addiction risk, and drug interactions, as well as the introduction of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition with related diagnostic changes, strongly encourage an updated appraisal of the use of BDZs in clinical practice. During a recent thematic event convened with the aim of approaching this topic in a critical manner, a group of young Italian psychiatrists attempted to highlight possible flaws in current teaching pathways, identify the main clinical pros and cons regarding current use of BDZs in clinical practice, and provide an updated overview of their use across specific clinical areas and patient populations. The main results are presented and discussed in this review. PMID- 26257530 TI - Introduction for Proceedings volume of 16(th) International Congress of Myriapodology. PMID- 26257531 TI - Type specimens of centipedes (Myriapoda, Chilopoda) in the National Museum, Prague (Czech Republic). AB - The centipede collection in the National Museum in Prague contains type material of 16 taxa (14 species and two subspecies), of which 15 were described by Ludek J. Dobroruka and one by Karl W. Verhoeff: Allothereuawilsonae Dobroruka, 1979; Chinobiusalenae Dobroruka, 1980; Lithobiuscorrigendus Dobroruka, 1988; Lithobiuscreticus Dobroruka, 1977; Lithobiuserythrocephalusmohelensis Dobroruka, 1959; Lithobiusevae Dobroruka, 1958; Lithobiusmagurensis Dobroruka, 1971; Lithobiuspurkynei Dobroruka, 1957; Lithobiustatricus Dobroruka, 1958; Lithobiustatricusmonounguis Dobroruka, 1958; Monotarsobiushomolaci Dobroruka, 1971; Monotarsobiuskrali Dobroruka, 1979; Pachymeriumdilottiae Dobroruka, 1976; Pachymeriumhanzaki Dobroruka, 1976; Scolopendraaztecorum Verhoeff, 1934 and Strigamiaolympica Dobroruka, 1977. Of these 16 taxa, five were described from the Czech Republic, three from Slovakia and eight from other countries (Greece, Iraq, Kyrgyzstan, Mexico, Nepal, Russia and Uzbekistan). The eight taxa described from the Czech and Slovak Republics are now considered as junior synonyms but the eight taxa described from the other countries are still valid. PMID- 26257532 TI - First results of the German Barcode of Life (GBOL) - Myriapoda project: Cryptic lineages in German Stenotaenialinearis (Koch, 1835) (Chilopoda, Geophilomorpha). AB - As part of the German Barcode of Life (GBOL) Myriapoda program, which aims to sequence the COI barcoding fragment for 2000 specimens of Germany's 200 myriapod species in the near future, 44 sequences of the centipede order Geophilomorpha are analyzed. The analyses are limited to the genera Geophilus Leach, 1814 and Stenotaenia Koch, 1847 and include a total of six species. A special focus is Stenotaenia, of which 19 specimens from southern, western and eastern Germany could be successfully sequenced. The Stenotaenia data shows the presence of three to four vastly different (13.7-16.7% p-distance) lineages of the genus in Germany. At least two of the three lineages show a wide distribution across Germany, only the lineage including topotypes of Stenotaenialinearis shows a more restricted distribution in southern Germany. In a maximum likelihood phylogenetic analysis the Italian species Stenotaenia 'sorrentina' (Attems, 1903) groups with the different German Stenotaenialinearis clades. The strongly different Stenotaenialinearis lineages within Germany, independent of geography, are a strong hint for the presence of additional, cryptic Stenotaenia species in Germany. PMID- 26257533 TI - Molecular-based estimate of species number, phylogenetic relationships and divergence times for the genus Stenotaenia (Chilopoda, Geophilomorpha) in the Italian region. AB - Stenotaenia is one of the largest and most widespread genera of geophilid centipedes in the Western Palearctic, with a very uniform morphology and about fifteen species provisionally recognized. For a better understanding of Stenotaenia species-level taxonomy, we have explored the possibility of using molecular data. As a preliminary assay, we sampled twelve populations, mainly from the Italian region, and analyzed partial sequences of the two genes COI and 28S. We employed a DNA-barcoding approach, complemented by a phylogenetic analysis coupled with divergence time estimation. Assuming a barcoding gap of 10 16% K2P pairwise distances, we found evidence for the presence of at least six Stenotaenia species in the Italian region, which started diverging about 50 million years ago, only partially matching with previously recognized species. We found that small-sized oligopodous species belong to a single clade that originated about 33 million years ago, and obtained some preliminary evidence of the related genus Tuoba being nested within Stenotaenia. PMID- 26257534 TI - Steps towards a phylogeny of the pill millipedes: non-monophyly of the family Protoglomeridae, with an integrative redescription of Eupeyerimhoffiaarchimedis (Diplopoda, Glomerida). AB - Eupeyerimhoffiaarchimedis (Strasser, 1965) is redescribed based on several specimens collected at a number of sites close to the type locality on Sicily, Italy. Scanning electron microscopy is used to illustrate several unusual morphological characters for a member of the Glomerida for the first time. A fragment of the mitochondrial COI gene (668bp) is sequenced for the first time in Eupeyerimhoffia to provide a species-specific barcode and to gain first insights into the genetic distances between the genera in the widespread family Protoglomeridae. The novel sequences are compared to representatives of all other genera of the family: Protoglomerisvasconica (Brolemann, 1897) from northern Spain, the dwarfed Glomerellinalaurae Silvestri, 1908 from Italy and Glomeroidesprimus (Silvestri, 1929) from western North America. The addition of COI sequences from the two other families of the Glomerida renders the family Protoglomeridae paraphyletic with Glomeroidesprimus being more closely related to Glomeridellaminima (Latzel, 1884) than to the other genera in the family. The large genetic distances (13.2-16.8%) between Eupeyerimhoffia and the other genera in the order, as well as its unusual morphological characters, including unique morphological adaptations to roll into a ball, are probably an indication of the old age of the group. PMID- 26257535 TI - Species limits and phylogeography of Newportia (Scolopendromorpha) and implications for widespread morphospecies. AB - The genus Newportia Gervais, 1847, includes some 60 nominal species distributed in the Caribbean islands and from Mexico to central South America. Modern keys to species and subspecies are available, greatly facilitating identification, but some species are based on few specimens and have incomplete documentation of taxonomically-informative characters. In order to explore genetic variability and evolutionary relationships within geographically-widespread morphospecies, specimens of Newportia (Newportia) stolli (Pocock, 1896) and Newportia (Newportia) divergens Chamberlin, 1922, two nominal species distinguished principally by differences in suture patterns on T1, were sequenced for mitochondrial 16S rRNA and cytochrome c oxidase subunit I (COI) genes from populations in southern Mexico, Guatemala, Honduras and Brazil. Newportia (Newportia) stolli is paraphyletic with respect to Newportia (Newportia) divergens within a clade from Guatemala, Honduras, and Chiapas (Mexico), most trees being consistent with a single loss of a connection between the anterior transverse suture on T1, whereas specimens of "Newportia (Newportia) stolli" from Brazil are not closely allied to those from the Mesomerican type area. The widespread morphospecies Newportia (Newportia) monticola Pocock, 1890, was sequenced for the same loci from populations in Costa Rica, Colombia and Brazil, finding that specimens from these areas do not unite as a monophyletic group. Samples of Newportia (Newportia) oreina Chamberlin, 1915, from different regions of Mexico form geographic clusters that resolve as each other's closest relatives. These results suggest that some widespread species of Newportia may be taxa of convenience more so than natural groupings. In several cases geographic proximity fits the phylogeny better than taxonomy, suggesting that non monophyletic species do not result from use of inappropriate molecular markers. Molecular identification is possible for specimens missing taxonomically informative morphological characters, notably damaged specimens that lack the ultimate leg pair, a protocol that may also apply to other taxonomically difficult genera that are prone to damage (such as Cryptops). PMID- 26257536 TI - Cave Diplopoda of southern China with reference to millipede diversity in Southeast Asia. AB - The diversity of Diplopoda in caves of southern China is remarkably high, often 5 6 species per cave, consisting mostly of local endemics and presumed troglobionts. These are evidently biased to just a few lineages, mainly members of the orders Chordeumatida and Callipodida, the families Cambalopsidae (Spirostreptida) and Haplodesmidae (Polydesmida) or the genera Pacidesmus, Epanerchodus and Glenniea (all Polydesmida, Polydesmidae), Trichopeltis (Polydesmida, Cryptodesmidae), Dexmoxytes (Polydesmida, Paradoxosomatidae) and Hyleoglomeris (Glomerida, Glomeridae). All these taxa, especially the Paradoxosomatidae and Cambalopsidae (usually amounting to about 60% and 10% of the total species diversity in the Oriental fauna, respectively), are moderately to highly speciose across Southeast Asia, being largely epigean. However, the epigean Diplopoda of southern China are yet badly understudied, since much of the collecting and taxonomic exploration efforts still focus on cavernicoles. The Oriental Region is the only biogeographic realm globally that harbours all 16 orders of Diplopoda, of which 14 have already been encountered in China and/or the immediately adjacent parts of Indochina. Thus, China may actually prove to support no less than 1,000 millipede species of various origins, mainly Oriental and Palaearctic. PMID- 26257537 TI - At the end of the rope: Geophilushadesi sp. n. - the world's deepest cave dwelling centipede (Chilopoda, Geophilomorpha, Geophilidae). AB - A new geophilomorph centipede, Geophilushadesi sp. n., is described from caves in the Velebit Mountain, central Croatia. Together with Geophiluspersephones Foddai & Minelli, 1999, described from Pierre Saint-Martin cave in France, they are the only two remarkably troglomorphic geophilomorphs hitherto known. The new species apparently belongs to a group of Geophilus species inhabiting mainly Western and Southern Europe, with a uniquely modified pretarsus in the second maxillae. Geophilushadesi sp. n. shows unusual traits, some of which commonly found in troglobitic arthropods, including exceptionally elongated antennae, trunk segments and leg claws. The species is described upon specimens found in two caves at a depth below -250 m. Another two specimens apparently belonging to the same species have been recorded in another deep vertical cave at -980 m and -1100 m. The latter represents the world's deepest record of Chilopoda as a whole. PMID- 26257538 TI - Millipedes faced with drought: the life cycle of a Mediterranean population of Ommatoiulussabulosus (Linnaeus) (Diplopoda, Julida, Julidae). AB - Growth, development and life-cycle duration of the millipede Ommatoiulussabulosus (f.aimatopodus) were studied in a Mediterranean shrubland of southern France and compared with previous data from northwest Europe. Changes in the proportions of stadia during the course of the year were analysed in several generations. The results show that stadia VII and VIII are consistently reached after the first year of growth, and stadia IX and X after the second year. First reproduction may occur at the age of two years in males reaching maturity at stadium X, but not until the age of three in those reaching maturity at stadia XI and XII. Reproduction cannot occur until at least the age of three in females, which carry mature eggs from stadium XI onwards. In comparison with more northern populations, life-cycle duration is not shorter in the Mediterranean population but there are marked differences in its phenology: the breeding period is in autumn, so that juveniles of stadia II to VI are never faced with the summer drought, and larger individuals are mostly inactive in summer; moreover, all individuals moult once every winter. The results illustrate how julid millipedes of humid temperate regions could respond to higher temperatures and drier summer conditions in the context of climate change. PMID- 26257539 TI - Centipede (Chilopoda) richness and diversity in the Bug River valley (Eastern Poland). AB - The main aim of the survey was to describe the diversity and richness of Chilopoda in the selected area of the Bug River valley. The study sites were located in two regions differing in the shape of the valley, the presence of thermophilous habitats and the size of riparian forests. Pitfall traps were used as a sampling method. As a result, 444 specimens belonging to 12 centipede species of two orders - Geophilomorpha (four species) and Lithobiomorpha (eight species) were caught. Lithobius (Monotarsobius) curtipes C.L.Koch, 1847, Pachymeriumferrugineum (C.L.Koch, 1835), Lamyctes (Lamyctes) emarginatus (Newport, 1844) and Lithobius (Monotarsobius) dudichi Loksa, 1947 were the most common and the most numerous species. Of particular note is Lithobiusdudichi found in Poland for the first time and previously known based on a single specimen. Two to 10 Chilopoda species were found in each habitat under investigation. The greatest species richness was found in thermophilous thickets (10 species), sandy grasslands (eight), xerothermic grasslands (eight) and mesic meadows (six). The fewest number of species (two) was found in rushes at oxbows and in wet meadows. We found differences in the species composition and the number of Chilopoda between the lower (102 specimens, six species) and the middle (324 specimens, 11 species) section of the river valley. Our results confirm the need to protect xerothermic habitats, unique almost throughout entire Central Europe, which due to their distribution and their small area covered are fairly easily subject to the process of destruction. PMID- 26257540 TI - Distribution of millipedes along an altitudinal gradient in the south of Lake Teletskoye, Altai Mts, Russia (Diplopoda). AB - The distribution of millipedes along an altitudinal gradient in the south of Lake Teletskoye, Altai, Russia based on new samples from the Kyga Profile sites, as well as on partly published and freshly revised material (Mikhaljova et al. 2007, 2008, 2014, Nefedieva and Nefediev 2008, Nefediev and Nefedieva 2013, Nefedieva et al. 2014), is established. The millipede diversity is estimated to be at least 15 species and subspecies from 10 genera, 6 families and three orders. The bulk of species diversity is confined both to low- and mid-mountain chern taiga forests and high-mountain shrub tundras, whereas the highest numbers, reaching up to 130 ind./m2, is shown in subalpine Pinussibirica sparse growths. Based on clustering studied localities on species diversity similarity two groups of sites are defined: low-mountain sites and subalpine sparse growths of Pinussibirica ones. PMID- 26257541 TI - Centipede assemblages along an urbanization gradient in the city of Heraklion, Crete (Greece). AB - Global urbanization is a major force that causes alteration and loss of natural habitats. Urban ecosystems are strongly affected by humans and there is a gradient of decreasing human influence from city centers to natural habitats. To study ecological changes along this continuum, researchers introduced the urban rural gradient approach. The responses of centipedes to an urbanization gradient (urban-suburban-rural areas) were studied using pitfall traps in and near the city of Heraklion, in the island of Crete, Greece, from November 2010 to November 2011. Our results do not support the intermediate disturbance hypothesis, in which suburban areas located in the transitional zone between urban and rural habitats failed to indicate significant increase in terms of species richness and diversity. PMID- 26257542 TI - Distribution of millipedes (Myriapoda, Diplopoda) along a forest interior - forest edge - grassland habitat complex. AB - We studied the distribution of millipedes in a forest interior-forest edge grassland habitat complex in the Hajdusag Landscape Protection Area (NE Hungary). The habitat types were as follows: (1) lowland oak forest, (2) forest edge with increased ground vegetation and shrub cover, and (3) mesophilous grassland. We collected millipedes by litter and soil sifting. There were overall 30 sifted litter and soil samples: 3 habitat types * 2 replicates * 5 soil and litter samples per habitats. We collected 9 millipede species; the most abundant species was Glomeristetrasticha, which was the most abundant species in the forest edge as well. The most abundant species in the forest interior was Kryphioiulusoccultus, while the most abundant species in the grassland was Megaphyllumunilineatum. Our result showed that the number of millipede species was significantly lower in the grassland than in the forest or in the edge, however there were no significant difference in the number of species between the forest interior and the forest edge. We found significantly the highest number of millipede individuals in the forest edge. There were differences in the composition of the millipede assemblages of the three habitats. The results of the DCCA showed that forest edge and forest interior habitats were clearly separated from the grassland habitats. The forest edge habitat was characterized by high air temperature, high soil moisture, high soil pH, high soil enzyme activity, high shrub cover and low canopy cover. The IndVal and the DCCA methods revealed the following character species of the forest edge habitats: Glomeristetrasticha and Leptoiuluscibdellus. Changes in millipede abundance and composition were highly correlated with the vegetation structure. PMID- 26257543 TI - Hay-bait traps are a useful tool for sampling of soil dwelling millipedes and centipedes. AB - Some species of centipedes and millipedes inhabit upper soil layers exclusively and are not recorded by pitfall trapping. Because of their sensitivity to soil conditions, they can be sampled quantitatively for evaluation of soil conditions. Soil samples are heavy to transport and their processing is time consuming, and such sampling leads to disturbance of the soil surface which land-owners do not like. We evaluated the use of hay-bait traps to sample soil dwelling millipedes and centipedes. The effectiveness of this method was found to be similar to the effectiveness of soil sampling. Hay-bait traps installed for 8-10 weeks can substitute for direct soil sampling in ecological and inventory studies. PMID- 26257544 TI - New records of Lophoproctuscoecus Pocock, 1894 (Diplopoda, Polyxenida, Lophoproctidae) extend the range of the genus Lophoproctus. AB - The geographic distribution of the genus Lophoproctus Pocock, 1894 has greatly expanded with new records of the species Lophoproctuscoecus Pocock, 1894, together with the reassignment of a number of millipedes formerly identified as Lophoproctuslucidus (Chalande, 1888). Lophoproctuscoecus was found to be the sole representative of the family Lophoproctidae in collections examined from Crimea and the Caucasian region. The species was also identified from Iran and Kyrgyzstan. Lophoproctus specimens collected in Italy by Verhoeff were reassigned as Lophoproctuscoecus with the exception of one specimen of Lophoproctusjeanneli (Brolemann, 1910) from Capri. These data were combined with all available information from the literature to look at the pattern of distribution of the four species in the genus. The range of the genus Lophoproctus extends from Portugal to Central Asia. Lophoproctuscoecus is widespread from Italy eastward, while the morphologically very similar species Lophoproctuslucidus is confined to France and northern Africa. The two species have a narrow overlap in the Alpes Maritimes region of France. Lophoproctusjeanneli has a scattered coastal distribution around the Mediterranean Sea. The troglobitic species Lophoproctuspagesi (Conde, 1982) has only been recorded from a cave on Majorca, Spain. PMID- 26257545 TI - The current knowledge on centipedes (Chilopoda) in Slovenia: faunistic and ecological records from a national database. AB - In spite of Slovenia's very high biodiversity, it has only a few animal groups that have been significantly investigated and are well known in this area. Slovenian researchers have studied only about half of the species known to be living in the country (Mrsic 1997), but among well investigated species are centipedes. All available data about centipedes in Slovenia collected from 1921 to 2014 have been consolidated and constitute a general electronic database called "CHILOBIO", which was created to provide an easy overview of the Slovenian centipede fauna and to allow entry and interpretation of new data collected in future research. The level of investigation has been studied with this database, in conjunction with a geographic information system (GIS). In the study period, 109 species were identified from 350 localities in 109 of the 236 UTM 10 * 10 km quadrants which cover the study area. The south-central part of the country has been the subject of the best investigations, whereas there is an absence of data from the south-eastern, eastern and north-eastern regions The highest number of species (52) has been recorded near the Iska valley (Central Slovenia, quadrant VL68). In 48% of the UTM quadrants investigated fewer than 10 species were recorded and just 5 species were found in one locality. Seventeen species were reported only in the Dinaric region, 4 in the Prealpine-subpannonian region and 7 in the Primorska-submediterranean region. PMID- 26257546 TI - Interaction of the tracheal tubules of Scutigeracoleoptrata (Chilopoda, Notostigmophora) with glandular structures of the pericardial septum. AB - Notostigmophora (Scutigeromorpha) exhibit a special tracheal system compared to other Chilopoda. The unpaired spiracles are localized medially on the long tergites and open into a wide atrium from which hundreds of tracheal tubules originate and extend into the pericardial sinus. Previous investigators reported that the tracheal tubules float freely in the hemolymph. However, here we show for the first time that the tracheal tubules are anchored to a part of the pericardial septum. Another novel finding is this part of the pericardial septum is structured as an aggregated gland on the basis of its specialized epithelium being formed by hundreds of oligocellular glands. It remains unclear whether the pericardial septum has a differently structure in areas that lack a connection with tracheal tubules. The tracheal tubules come into direct contact with the canal cells of the glands that presumably secrete mucous substances covering the entire luminal cuticle of the tracheal tubules. Connections between tracheae and glands have not been observed in any other arthropods. PMID- 26257547 TI - Tentorial mobility in centipedes (Chilopoda) revisited: 3D reconstruction of the mandibulo-tentorial musculature of Geophilomorpha. AB - Mandibular mechanisms in Geophilomorpha are revised based on three-dimensional reconstructions of the mandibulo-tentorial complex and its muscular equipment in Dicellophiluscarniolensis (Placodesmata) and Hydroschendylasubmarina (Adesmata). Tentorial structure compares closely in the two species and homologies can be proposed for the 14/17 muscles that attach to the tentorium. Both species retain homologues of muscles that in other Pleurostigmophora are traditionally thought to cause swinging movements of the tentorium that complement the mobility of the mandibles. Although the original set of tentorial muscles is simplified in Geophilomorpha, the arrangement of the preserved homologues conforms to a system of six degrees of freedom of movement, as in non-geophilomorph Pleurostigmophora. A simplification of the mandibular muscles is confirmed for Geophilomorpha, but our results reject absence of muscles that in other Pleurostigmophora primarily support see-saw movements of the mandibles. In the construction of the tentorium, paralabial sclerites seem to be involved in neither Placodesmata nor Adesmata, and we propose their loss in Geophilomorpha as a whole. Current insights on the tentorial skeleton and its musculature permit two alternative conclusions on their transformation in Geophilomorpha: either tentorial mobility is primarily maintained in both Placodesmata and Adesmata (contrary to Manton's arguments for immobility), or the traditional assumption of the tentorium as being mobile is a misinterpretation for Pleurostigmophora as a whole. PMID- 26257548 TI - On the function of the ultimate legs of some Scolopendridae (Chilopoda, Scolopendromorpha). AB - The function of the variously shaped ultimate legs of Scolopendridae is briefly reviewed. Their function in Scolopendraheros Girard, 1853, Scolopendrasubspinipes Leach, 1815, Scolopendramorsitans (Linnaeus, 1758), Scolopendragalapagoensis Bollman, 1889, Scolopendrahainanum Kronmuller, 2012, Scolopendraspinosissima Kraepelin, 1903 Cormocephalusaurantiipes (Newport, 1844) and Ethmostigmustrigonopodus (Leach, 1817), in which they are least specialised has been investigated. Specimens were tapped with forceps on different parts of the trunk to simulate the attack of a predator. When tapped on the first third of the trunk (near the head), the centipedes attacked the forceps with their forcipules. When tapped on the last third or the ultimate legs, they adopted a warning position, raising the ultimate legs to display the ventral and medial prefemoral spines as well as the spined coxopleural processes. In some cases the centipedes attacked the forceps with the claws of the ultimate legs by chopping down on them after lifting the legs high into the warning position. When tapped in the mid part of the trunk, the centipedes curled sideways to reach the forceps with their forcipules and ultimate legs simultaneously. Scolopendragalapagoensis not only lifted the ultimate legs into the warning position but also the last 3-4 pairs of locomotory legs, presenting their distodorsal prefemoral spines. This resembles the warning posture of some spiders. In addition to their function in warning behaviour, defensive stabbing, ritualised meeting reactions and during courtship behaviour, the ultimate legs may in addition act as hooks and perhaps be involved in species recognition. No evidence was found that the ultimate legs are used to catch prey, nor of prey or predators being held between the prefemora. PMID- 26257549 TI - A new genus and species of octocoral with aragonite calcium-carbonate skeleton (Octocorallia, Helioporacea) from Okinawa, Japan. AB - A new genus and species of octocoral with a calcium-carbonate skeleton, Naniporakamurai sp. n., is described from a shallow coral reef in Okinawa, Japan. Contrary to most octocorals, the skeleton is composed of crystalline aragonite as in blue coral Heliopora. The results of molecular phylogenetic analyses of sequences of mtMutS, COI, and ITS1-5.8s-ITS2-28S region suggest Nanipora gen. n. specimens should be included in order Helioporacea. Based on morphological results compared with other Helioporacea including the genus Epiphaxum (family Lithotelestidae), we establish the new genus Nanipora within Lithotelestidae. This is the first time that a close molecular phylogenetic relationship between Heliopora and a related genus within Helioporacea has been revealed. PMID- 26257550 TI - New data on two remarkable Antarctic species Amblydorylaimusisokaryon (Loof, 1975) Andrassy, 1998 and Pararhyssocolpusparadoxus (Loof, 1975), gen. n., comb. n. (Nematoda, Dorylaimida). AB - The taxonomic position of two antarctic dorylaimid species Amblydorylaimusisokaryon (Loof, 1975) Andrassy, 1998 and Pararhyssocolpusparadoxus (Loof, 1975), gen. n., comb. n. are discussed on the basis of morphological, including SEM study, morphometric, postembryonic and sequence data of 18S rDNA and the D2-D3 expansion fragments of large subunit rDNA. The evolutionary trees inferred from 18S sequences show insufficient resolution to determine the assignment of the two species to particular families, moreover Pararhyssocolpusparadoxus gen. n., comb. n. (=Rhyssocolpusparadoxus) previously regarded as a member of Nordiidae or Qudsianematidae, showed distant relationship both to Rhyssocolpusvinciguerrae and Eudorylaimus spp. The phylogram inferred from 28S sequences revealed that Amblydorylaimusisokaryon is a member of a well-supported group comprised of several Aporcelaimellus spp., while, no close relationships could be revealed for the Pararhyssocolpusparadoxus gen. n., comb. n. to any nematode genus. On the basis of molecular data and morphological characteristics, some taxonomic changes are proposed. Amblydorylaimusisokaryon is transferred from family Qudsianematidae to family Aporcelaimidae, and a new monotypic genus Pararhyssocolpus gen. n. is proposed, attributed to Pararhyssocolpidaefam. n. The diagnosis of the new family is provided together with emended diagnosis of the genera Amblydorylaimus and Pararhyssocolpus gen. n. Data concerning distribution of these endemic genera in the Antarctic region are also given. PMID- 26257551 TI - In the shadow of a megalopolis, a new Flexamia from a threatened grass species in the New Jersey Pine Barrens (Hemiptera, Cicadellidae, Deltocephalinae, Paralimnini). AB - A previously unknown species of the North American leafhopper genus Flexamia, Flexamiawhitcombi sp. n., is described from pinebarren smokegrass (Muhlenbergiatorreyana (Schult.) Hitchc.), a state-listed threatened grass in the New Jersey Pine Barrens. The serrata species group, to which it belongs, is redefined and a key to the species of the group is provided. This is the first reported insect association with Muhlenbergiatorreyana. PMID- 26257552 TI - Tumidusternus, a new genus of Aspidimerini from China (Coleoptera, Coccinellidae). AB - Tumidusternus gen. n., along with Tumidusternusfujianensis sp. n. (Coleoptera, Coccinellidae, Aspidimerini) from China is described and illustrated. A key to the tribe Aspidimerini is given. PMID- 26257553 TI - Contribution to the genus Xanthocorus Miyatake (Coleoptera, Coccinellidae, Chilocorini). AB - The genus Xanthocorus Miyatake, 1970 consists of three species from China, including two new species described here: Xanthocorusnigrosuturalis sp. n. and Xanthocorusmucronatus sp. n. A key to identification of species is given. Diagnoses, detailed descriptions, illustrations, and distributions are provided. PMID- 26257554 TI - A review of the omicrine genera Omicrogiton, Mircogioton and Peratogonus of China (Coleoptera, Hydrophilidae, Sphaeridiinae). AB - The Chinese species of the genera Omicrogiton Orchymont, 1919, Peratogonus Sharp, 1884 and Mircogioton Orchymont, 1937 are reviewed, diagnosed and keyed. Mircogioton and Omicrogiton are reported for the first time from China, Peratogonus for the first time for mainland China. Five species are recognized: Omicrogitoncoomani Balfour-Browne, 1939 (Guangdong, Hongkong), Omicrogitonhainanensis sp. n. (Hainan), Omicrogitonroberti sp. n. (Hainan), Mircogiotoncoomani Orchymont, 1937 (Yunnan), and Peratogonusreversus Sharp, 1884 (Guangdong, Jiangxi, Taiwan). Lectotype of Omicrogitoncoomani is designated. Mircogiotoncognitus (Malcolm, 1981), syn. n. is considered a junior subjective synonym of Mircogiotoncoomani Orchymont, 1939. Species of Mircogioton and Omicrogiton inhabit decaying banana trunks, whereas Peratogonusreversus was always collected from moist forest leaf litter. PMID- 26257555 TI - Two new species of Paramesosciophilodes (Diptera, Nematocera, Mesosciophilidae) from the Middle Jurassic of China. AB - Two new species, Paramesosciophilodesbellus sp. n. and Paramesosciophilodesrarissima sp. n., from the Jiulongshan Formation at Daohugou Village, Inner Mongolia, China, are described in the extinct family Mesosciophilidae. Altogether seven genera with 21 species of mesosciophilids have been described from the Jurassic of Siberia and Kazakhstan, the Lower Cretaceous of Transbaikalia, and the Middle Jurassic of Inner Mongolia. An emended generic diagnosis of Paramesosciophilodes and a list of known taxa of mesosciophilids are provided. PMID- 26257556 TI - Helminths of three species of opossums (Mammalia, Didelphidae) from Mexico. AB - From August 2011 to November 2013, 68 opossums (8 Didelphis sp., 40 Didelphisvirginiana, 15 Didelphismarsupialis, and 5 Philanderopossum) were collected in 18 localities from 12 Mexican states. A total of 12,188 helminths representing 21 taxa were identified (6 trematodes, 2 cestodes, 3 acanthocephalans and 10 nematodes). Sixty-six new locality records, 9 new host records, and one species, the trematode Brachylaimadidelphus, is added to the composition of the helminth fauna of the opossums in Mexico. These data, in conjunction with previous records, bring the number of taxa parasitizing the Mexican terrestrial marsupials to 41. Among these species, we recognized a group of helminths typical of didelphids in other parts of the Americas. This group is constituted by the trematode Rhopaliascoronatus, the acanthocephalan Oligacanthorhynchusmicrocephalus and the nematodes Cruziatentaculata, Gnathostomaturgidum, and Turgidaturgida. In general, the helminth fauna of each didelphid species showed a stable taxonomic composition with respect to previously sampled sites. This situation suggests that the rate of accumulation of helminth species in the inventory of these 3 species of terrestrial marsupials in the Neotropical portion of Mexico is decreasing; however, new samplings in the Nearctic portion of this country will probably increase the richness of the helminthological inventory of this group of mammals. PMID- 26257557 TI - Five new Platocoelotes species (Araneae, Agelenidae) from caves in southern China. AB - Five new Platocoelotes species are described based on both sexes collected from caves in southern China. They are: Platocoelotesluoi sp. n. from Jiangxi, Platocoelotesqinglinensis sp. n. from Yunnan, Platocoelotesshuiensis sp. n. from Guizhou, Platocoelotestianyangensis sp. n. from Sichuan and Platocoelotesxianwuensis sp. n. from Hubei. PMID- 26257558 TI - The genus Trachionus Haliday, 1833 (Hymenoptera, Braconidae, Alysiinae) new for China, with description of four new species. AB - The genus Trachionus Haliday, 1833 (Hymenoptera, Braconidae, Alysiinae, Dacnusini) is reported for the first time from China. The genus is represented by four new species from Shaanxi province (NW China), which are described and illustrated. An identification key to the species in China is presented, a key to the genera of the Trachionus group and notes on the relationships with other Palaearctic species are added. PMID- 26257559 TI - What is Tetramoriumsemilaeve Andre, 1883? (Hymenoptera, Formicidae). AB - Tetramoriumsemilaeve Andre, 1883 is redescribed based on the type series and new material from terra typica (Pyrenees-Orientales). Lectotype worker is designated. Detailed descriptions of gyne and male are given. A review of material from the Mediterranean area suggests that in the past the name Tetramoriumsemilaeve has been applied to more than one species and the true Tetramoriumsemilaeve is common only in the western part of the Mediterranean basin. The structure of the male genitalia is the most reliable set of characters allowing a proper distinction of species in Tetramoriumsemilaeve species group. All names attributed to the former name "semilaeve" are discussed. PMID- 26257560 TI - A new species of Agaporomorphus Zimmermann, 1921 from Peru (Coleoptera, Dytiscidae, Copelatinae). AB - Agaporomorphusjulianeae sp. n. is described from the Biological Field Station Panguana, in Huanuco province of central Peru. The new species belongs to the Agaporomorphusknischi-group sensu Miller 2005. Together with Agaporomorphusknischi Zimmermann, 1921 and Agaporomorphuscolberti Miller & Wheeler, 2008 this is the third species of the genus with broadly enlarged male antennomeres. The new species can be separated from Agaporomorphuscolberti and Agaporomorphusknischi by the smaller please expanded male antennomere VIII, and the form of the median lobe. Important species characters (median lobe, male antennae, metafemur, colour pattern) of the new species and Agaporomorphusknischi are figured, and the habitat, a temporary blackwater forest pond, and its species rich water beetle coenosis are illustrated and described in detail. The Brazilian Agaporomorphusmecolobus Miller, 2001, only known from the type material from Sao Paulo, is here recorded for Minas Gerais. Habitus photos of four additional Agaporomorphus species and Hydrodytesopalinus (Zimmermann, 1921) are provided. Altogether ten species of Agaporomorphus are now known. PMID- 26257561 TI - Co1 DNA supports conspecificity of Geomyphiluspierai and G.barrerai (Coleoptera, Scarabaeidae, Aphodiinae) and is a good marker for their phylogeographic investigation in Mexican mountains. AB - Members of Geomyphilus are associated with rodent burrows, such as pocket gophers and prairie dogs. In Mexico, they are found in the mountains of the Mexican Volcanic Belt and in Sierra Madre Oriental. Our study aims to initiate the exploration of the dispersal modes of Geomyphiluspierai and Geomyphilusbarrerai from burrows of pocket gophers. In order to estimate the dispersal scale of the beetles, the utility of mitochondrial and nuclear molecular markers for studying the phylogeographic structure of this complex of species (Geomyphiluspierai and Geomyphilusbarrerai) was tested from 49 beetle individuals. High intraspecific and intra-mountain nucleotidic diversity was captured from this sample using Co1 mitochondrial sequences, whilst the ITS2 nuclear ribosomal sequence did not allow observing informative variation. Mitochondrial phylogenetic analysis revealed that the specific delineation between the two species under study was doubtful. In this preliminary study, Co1 was shown to be a good marker for elucidating dispersal routes of the burrowing rodent-associated beetles. PMID- 26257562 TI - A new species group in Megaselia, the lucifrons group, with description of a new species (Diptera, Phoridae). AB - With 1,400 described species, Megaselia is one of the most species-rich genera in the animal kingdom, and at the same time one of the least studied. An important obstacle to taxonomic progress is the lack of knowledge concerning the phylogenetic structure within the genus. Classification of Megaselia at the level of subgenus is incomplete although Schmitz addressed several groups of species in a series of monographs published from 1956 to 1981. Another problem is the lack of molecular phylogenetic analyses to support morphology-based conclusions. As a contribution towards addressing these problems, we here circumscribe a previously unrecognized monophyletic lineage of Megaselia consisting of species similar to Megaselialucifrons. We base this taxonomic decision on morphological study of an extensive phorid material from Sweden, complemented by molecular analyses of select exemplars using two markers (COI and 28S). We name the clade the lucifrons species group, and show that it contains three distinct species. Our results also demonstrate that Megaseliasubnitida Lundbeck, 1920, previously treated as a synonym of Megaselialucifrons Schmitz, 1918, is a separate species, and we remove it from synonymy. The third species in the group was previously unknown; we describe it here as Megaseliaalbalucifrons sp. n. PMID- 26257563 TI - A new flea of the genus Ctenidiosomus (Siphonaptera, Pygiopsyllidae) from Salta Province, Argentina. AB - A new species of flea of the genus Ctenidiosomus Jordan, 1931 (Siphonaptera: Pygiopsyllidae) is described from Phyllotisosilae J. A. Allen, 1901, from Salta Province, Argentina. This is the first time that Ctenidiosomus has been recorded in Argentina. A key to species of males of Ctenidiosomus is presented. PMID- 26257565 TI - Four new species of Desmiphorini (Coleoptera, Cerambycidae, Lamiinae). AB - Four new species of Desmiphorini are described: Desmiphora (Desmiphora) orozcoi, from Belize; Estolawappesi, from Bolivia; Estolaimitatrix, from Bolivia; and Gyrpanetesclarkei, from Bolivia. A key to the species of Gyrpanetes is provided, and Estolawappesi and Estolaimitatrix are included in an existing key. PMID- 26257564 TI - Taxonomy of the hyper-diverse ant genus Tetramorium Mayr in the Malagasy region (Hymenoptera, Formicidae, Myrmicinae) - first record of the T.setigerum species group and additions to the Malagasy species groups with an updated illustrated identification key. AB - In this study we provide an update to the taxonomy of the ant genus Tetramorium Mayr in Madagascar. We report the first record of the Tetramoriumsetigerum species group in Madagascar and describe the only Malagasy representative as Tetramoriumcavernicola sp. n., which is known only from a cave in Ankarana. In addition, we provide an overview of the 19 proposed Malagasy species groups, and discuss their zoogeography and relationships to other groups and larger lineages within the hyper-diverse genus Tetramorium. At present, we recognise a highly unique Malagasy Tetramorium fauna with 113 species endemic to the island of Madagascar out of a total of 125 translating into an endemism rate of 93%. We hypothesise that this fauna is based on one or a few colonisation events from the Afrotropical region, with subsequent adaptive radiation in Madagascar. Furthermore, we present an updated and illustrated identification key to the Tetramorium species groups in the Malagasy region. PMID- 26257566 TI - Termitotroxvenus sp. n. (Coleoptera, Scarabaeidae), a new blind, flightless termitophilous scarab from Cambodia. AB - Termitotroxvenus sp. n. is described from Cambodia and represents the second discovery of Termitotrox Reichensperger, 1915 from the Indo-Chinese subregion of the Indomalayan region. Most of the type series was collected from refuse dumps in fungus garden cells of Macrotermescf.gilvus (Hagen, 1858). Macrotermes Holmgren, 1910 was previously an unknown host of Termitotrox species. The new species is easily distinguished from all known congeners by having wing-shaped trichomes on the elytra and the larger body size, at 2.5 mm in length. We also describe the mouthparts to complement the description of the genus Termitotrox. PMID- 26257567 TI - New records of Limoniidae and Pediciidae (Diptera) from Croatia. AB - New records are provided for Limoniidae and Pediciidae from Croatia, with new distribution records for species in 12 different genera. Four genera and 18 species are newly recorded for Croatia. Until now, including this data, 87 Limoniidae and eight Pediciidae have been recorded from Croatia. In this paper we confirm presence of Ormosia (Oreophila) bergrothi (Strobl, 1895) and we give the first records of Dicranota (Paradicranota) pavida (Haliday, 1833) and Molophilus (Molophilus) repentinus Stary, 1971 from Balkan Peninsula. PMID- 26257569 TI - Australian Allograpta Osten Sacken (Diptera, Syrphidae). AB - Allograptaterraenovae sp. n. and Allograptanotiale sp. n. are described from Australia. Notes on the Australian species of Allograpta and an identification key to them are also given. The lectotype of Allograptajavana Wiedemann is designated, and the species Syrphuspallidus Bigot is synonymized under Allograptaaustralensis (Schiner). PMID- 26257568 TI - Mosquito species (Diptera, Culicidae) in three ecosystems from the Colombian Andes: identification through DNA barcoding and adult morphology. AB - Colombia, one of the world's megadiverse countries, has a highly diverse mosquito fauna and a high prevalence of mosquito-borne diseases. In order to provide relevant information about the diversity and taxonomy of mosquito species in Colombia and to test the usefulness of DNA barcodes, mosquito species collected at different elevations in the departments of Antioquia and Caldas were identified combining adult morphology and barcode sequences. A total of 22 mosquito species from eight genera were identified using these combined techniques. We generated 77 barcode sequences with 16 species submitted as new country records for public databases. We examined the usefulness of DNA barcodes to discriminate mosquito species from the Neotropics by compiling 1,292 sequences from a total of 133 species and using the tree-based methods of neighbor-joining and maximum likelihood. Both methodologies provided similar results by resolving 105 species of mosquitoes separated into distinct clusters. This study shows the importance of combining classic morphological methodologies with molecular tools to accurately identify mosquitoes from Colombia. PMID- 26257570 TI - Description of two new filtering carnivore Drusus species (Limnephilidae, Drusinae) from the Western Balkans. AB - Two new species of the genus Drusus (Trichoptera, Limnephilidae, Drusinae) from the Western Balkans are described. Additionally, observations on the biodiversity and threats to the region's endemic aquatic fauna are discussed. Drususkrpachi sp. n. is a micro-endemic of the Korab Mountains, Macedonia, and Drususmalickyi sp. n. is a micro-endemic of the Prokletije Mountains, Albania. Both new species are most similar to Drususmacedonicus but differ from the latter in the shape of segment IX, the shape of the tips of the intermediate appendages in lateral view, the shape of the inferior appendages, and the form and shape of the parameres. In addition, males of the European species of filtering carnivore Drusinae are diagnosed and illustrated, including Cryptothrixnebulicola McLachlan, Drususchrysotus Rambur, Drususdiscolor Rambur, Drususmacedonicus Schmid, Drususmeridionalis Kumanski, Drususmuelleri McLachlan, Drususromanicus Murgoci and Botosaneanu, and Drusussiveci Malicky. These additions to the Western Balkan fauna demonstrate the significance of this region for European biodiversity and further highlight the importance of faunistic studies in Europe. PMID- 26257571 TI - Four new species of Cymatodera Gray from central and southern Mexico (Coleoptera, Cleridae, Tillinae). AB - Four new species of Cymatodera are described from Mexico: Cymatoderatortuosa Burke & Rifkind, sp. n. from Hidalgo and Tamaulipas; Cymatoderaortegae Burke, sp. n. from Colima, Jalisco and Michoacan; Cymatoderagerstmeieri Burke & Rifkind, sp. n. from Chiapas; and Cymatoderamixteca Burke & Rifkind, sp. n. from Puebla and Guerrero. Male genitalia and other characters of taxonomic value are illustrated. PMID- 26257572 TI - A new, mesophotic Coryphopterus goby (Teleostei, Gobiidae) from the southern Caribbean, with comments on relationships and depth distributions within the genus. AB - A new species of western Atlantic Coryphopterus is described from mesophotic depths off Curacao, southern Caribbean. Coryphopteruscurasub sp. n., is similar to Coryphopterusdicrus in, among other features, having two prominent pigment spots of roughly equal intensity on the pectoral-fin base, the pelvic fins fused to form a disk, and no pelvic frenum. The two species can be differentiated by body depth (shallower in Coryphopteruscurasub at origin of dorsal fin and caudal peduncle); differences in the pigmentation on the head, trunk, and basicaudal region; and usually by total number of rays (spinous plus soft) in the second dorsal fin (10-11, usually 11, in Coryphopteruscurasub, 10 in Coryphopterusdicrus). Coryphopteruscurasub differs from other Coryphopterus species that have a prominent pigment spot on the lower portion of the pectoral fin base (Coryphopteruspunctipectophorus and Coryphopterusvenezuelae) in, among other features, lacking a pelvic frenum. Coryphopteruscurasub was collected between 70 and 80 m, the deepest depth range known for the genus. Collections of Coryphopterusvenezuelae at depths of 65-69 m extend the depth range of that species by approximately 50 m. Mitochondrial cytochrome c oxidase subunit I (COI) data corroborate the recognition of Coryphopteruscurasub as a distinct species but do not rigorously resolve its relationships within the genus. A revised key to the western Atlantic species of Coryphopterus is presented. PMID- 26257573 TI - Taxonomic etymology - in search of inspiration. AB - We present a review of the etymology of zoological taxonomic names with emphasis on the most unusual examples. The names were divided into several categories, starting from the most common - given after morphological features - through inspiration from mythology, legends, and classic literature but also from fictional and nonfictional pop-culture characters (e.g., music, movies or cartoons), science, and politics. A separate category includes zoological names created using word-play and figures of speech such as tautonyms, acronyms, anagrams, and palindromes. Our intention was to give an overview of possibilities of how and where taxonomists can find the inspirations that will be consistent with the ICZN rules and generate more detail afterthought about the naming process itself, the meaningful character of naming, as well as the recognition and understanding of names. PMID- 26257574 TI - Heterocycle-to-Heterocycle Route to Quinoline-4-amines: Reductive Heterocyclization of 3-(2-Nitrophenyl)isoxazoles. AB - A variety of quinoline-4-amines were synthesized from substituted 3-(2 nitrophenyl)isoxazoles utilizing Zn0 or Fe0 dust and HOAc via a reductive heterocyclization process. The starting isoxazoles were synthesized from readily available starting materials. A brief survey of functional groups tolerated in this reductive heterocyclization was performed and several 10-amino-3,4 dihydrobenzo[b][1,6]naphthyridin-1(2H)-one and 9-amino-3,4-dihydroacridin-1(2H) one examples were synthesized. PMID- 26257575 TI - Conformationally Constrained Penta(hetero)cyclic Molecular Architectures via Photoassisted Diversity-Oriented Synthesis. AB - Intramolecular cycloadditions of photogenerated azaxylylenes provide access to unprecedented polyheterocyclic scaffolds, suitable for subsequent postphotochemical modifications to further grow molecular complexity. Here we explore approaches to rapid "assembly" of novel photoprecursors with nitrogen/oxygen-rich tethers capable of producing potential pharmacophores and also compatible with subsequent 1,3-dipolar cycloadditions to furnish pentacyclic heterocycles with new structural cores, minimal number of rotatable bonds, and a high content of sp3 hybridized carbons. The modular "assembly" of the photoprecursors and potential variety of postphotochemical modifications of primary photoproducts provide framework for combinatorial implementation of this synthetic strategy. PMID- 26257576 TI - Studies Towards the Leucetta-derived Alkaloids Spirocalcaridine A and B - Possible Biosynthetic Implications. AB - An exploration of an abiotic approach to spirocalcaridines A and B is described centered on electrophile-induced dearomatizing spirocyclization of aryl enyne derivatives. Elaboration of the alpha-iodoenone via an Ullmann-like, copper catalyzed amidation provided a formamide which upon treatment with methylamine undergoes a dienol-arene rearrangement, providing the corresponding kealiinine like framework. This observation suggests a possible biosynthetic links between the spirocalcaridines and the naphthimidazole group of Leucetta alkaloids. PMID- 26257577 TI - A Convergent Synthesis of 6-O-Branched beta-Glucan Oligosaccharides. AB - beta-Glucans are important carbohydrate antigens on the surface of fungal cells useful for antifungal vaccine development. This paper has described a highly convergent and efficient strategy for the synthesis of structurally defined branched beta-glucan oligosaccharides that can be used for detailed studies of beta-glucans and for the design of beta-glucan-based vaccines. The strategy was highlighted by assembling the title compounds via preactivation-based glycosylation with thioglycosides as glycosyl donors. It was used to successfully prepare beta-glucan oligosaccharides that had a beta-1,3-linked nonaglucan backbone with beta-1,6-glucotetraose, beta-1,3-glucodiose and beta-1,3 glucotetraose branches at the 6-O-position of the nonaglucan central sugar unit. The structure and size of the glycosyl donors and acceptors used in the syntheses did not significantly affect the glycosylation efficiency, suggesting that the strategy can be generally useful for the synthesis of more complex structures. PMID- 26257578 TI - Chlorin e6 131:152-Anhydride: A Key Intermediate in Conjugation Reactions of Chlorin e6. AB - Since the patent for the photodynamic therapy agent Talaporfin (mono-L aspartylchlorin e6) was issued in 1987, confusion has existed regarding which of the three carboxylic acid groups in the chlorophyll degradation product, chlorin e6 (1), is modified in standard amino acid type conjugations (using DCC or EDC and an organic base) with amino acids and other biomolecules. Here it is shown that the site of conjugation is the central 152-carboxylic acid, such reactions proceeding in numerous examples via a 131,152-anhydride for which a high resolution X-ray structure is reported. Conjugation with eight oxygen and nitrogen nucleophiles, in every case, afforded the 152-conjugate, reinforcing the earlier conclusion that Talaporfin is the 152-aspartyl conjugate of chlorin e6 and suggesting that reports of 173-conjugation of chlorin e6 using stoichiometric peptide coupling procedures should be subjected to further scrutiny. PMID- 26257579 TI - Synthesis of 1,2,3-triazol-1-yl-methaneboronic acids via click chemistry: an easy access to a new potential scaffold for protease inhibitors. AB - Stereoselective synthesis of previously unreported 1,2,3-triazol-1-yl methaneboronic acids has been achieved from azidomethaneboronates by Copper catalyzed Azide-Alkyne Cycloaddition (CuAAC). The proximity of the cycloaddition reaction center to the boronic group is not detrimental for the stability of the sp3-carbon-boron bond nor to the stereoisomeric composition, further expanding the field of application of click chemistry to new boronate substrates and offering a new potential scaffold for protease inhibitors. PMID- 26257580 TI - One-pot directed alkylation/deprotection strategy for the synthesis of substituted pyrrole[3,4-d]pyridazinones. AB - In the course of an SAR study of pyrrole[3,4-d]pyridazinones we optimized conditions for a one pot directed lithiation / alkylation reaction that also promoted in situ cleavage of a Boc-protecting group on the pyrrole ring. The efficiency of the process allowed access to a number of substituted analogues of interest as possible antitumor agents. PMID- 26257581 TI - Aerobic and anaerobic reduction of birnessite by a novel Dietzia strain. AB - BACKGROUND: Mn oxides occur in a wide variety of geological settings and exert considerable influences on the components and chemical behaviors of sediments and soils. Microbial reduction of Mn oxides is an important process found in many different environments including marine and freshwater sediments, lakes, anoxic basins, as well as oxic-anoxic transition zone of ocean. Although the pathway of Mn anaerobic reduction by two model bacteria, Geobacter and Shewanella, has been intensively studied, Mn bio-reduction is still the least well-explored process in nature. Particularly, reduction of Mn oxides by other bacteria and in the presence of O2 has been fewly reported in recent publishes. RESULTS: A series of experiments were conducted to understand the capability of Dietzia DQ12-45-1b in bioreduction of birnessite. In anaerobic systems, Mn reduction rate reached as high as 93% within 4 weeks when inoculated with 1.0 * 10(10) cells/mL Dietzia DQ12-45-1b strains. Addition of AQDS enhanced Mn reduction rate from 53 to 91%. The anaerobic reduction of Mn was not coupled by any increase in bacterial protein concentration, and the reduction rate in the stable stage of day 2-14 was found to be in good proportion to the protein concentration. The anaerobic reduction of birnessite released Mn(II) either into the medium or adsorbed on the mineral or bacteria surface and resulted in the dissolution of birnessite as indicated by XRD, SEM and XANES. Under aerobic condition, the reduction rate was only 37% with a cell concentration of 1.0 * 10(10) cells/mL, much lower than that in parallel anaerobic treatment. Bacterial growth under aerobic condition was indicated by time-course increase of protein and pH. In contrast to anaerobic experiments, addition of AQDS decreased Mn reduction rate from 25 to 6%. The reduced Mn(II) combined with carbon dioxide produced by acetate metabolism, as well as an alkaline pH environment given by cell growth, finally resulted in the formation of Mn(II)-bearing carbonate (kutnohorite), which was verified by XRD and XANES results. The system with the highest cell concentration of 1.0 * 10(10) cells/mL gave rise to the most amount of kutnohorite, while concentration of Mn(II) produced with cell concentration of 6.2 * 10(8) cells/mL was too low to thermodynamically favor the formation of kutnohorite but result in the formation of aragonite instead. CONCLUSION: Dietzia DQ12-45-1b was able to anaerobically and aerobically reduce birnessite. The rate and extent of Mn(IV) reduction depend on cell concentration, addition of AQDS or not, and presence of O2 or not. Meanwhile, Mn(IV) bioreduction extent and suspension conditions determined the insoluble mineral products. PMID- 26257582 TI - Expression and clinicopathological significance of miR-193a-3p and its potential target astrocyte elevated gene-1 in non-small lung cancer tissues. AB - BACKGROUND: Aberrant expression of miR-193a-3p and astrocyte elevated gene-1 (AEG 1) have been revealed to be related to the tumorigenesis of various cancers, including non-small cell lung cancer (NSCLC). However, the significance of miR 193a-3p and its correlation with AEG-1 in NSCLC has not been explored. The purpose of this study was to evaluate the association between miR-193a-3p and AEG 1 and their relationship with the clinicopathological features in NSCLC patients. METHODS: Via online in silico prediction, complementary sequences were found between miR-193a-3p and the 3'-untranslated region of AEG-1. Three independent cohorts were applied in the current study. Firstly, miR-193a-3p level was detected in 125 cases of NSCLC with quantitative real-time PCR (qRT-PCR). Secondly, AEG-1 protein level was evaluated in 339 cases of lung cancers with immunohistochemistry. Finally, the relationship between miR-193a-3p and AEG-1 protein expression was verified in another group with 65 cases of NSCLC. RESULTS: The results showed that miR-193a-3p level was decreased in NSCLC tissues and significantly negatively related to tumor size (r = -0.277, P = 0.002), clinical TNM stage (r = -0.226, P = 0.011), lymph node metastasis (r = -0.186, P = 0.038), epidermal growth factor receptor (EGFR) protein level (r = -0.272, P = 0.041). On the contrary, AEG-1 protein expression was up-regulated in NSCLC and positively relative to tumor size (r = 0.240, P < 0.001), TNM stages (r = 0.164, P = 0.002) and lymph node metastasis (r = 0.232, P < 0.001) in NSCLC patients. In addition, miR-193a-3p was found to be inversely associated with AEG-1 protein expression in the third cohort (r = -0.564, P < 0.001). CONCLUSION: In conclusion, miR-193a-3p and AEG-1 might be responsible for the carcinogenesis and aggressiveness of NSCLC. AEG-1 has the potential to be one of the targeted genes of miR-193a-3p. However, future in vitro and in vivo experiments are needed to verify this hypothesis. PMID- 26257583 TI - Emerald dragon bites vs veggie beans: Fun food names increase children's consumption of novel healthy foods. AB - Caregivers often struggle with food neophobia on the part of young children. This study examined whether labeling novel healthy foods with fun names would increase children's willingness to try those foods and encourage them to eat more of those foods in a child care setting. Thirty-nine toddler and preschool age children (mean age = 3.9 years) were served each of three foods twice, once labeled with a fun name and once with a healthy name. Percentage of the food consumed by each child was recorded. Overall, children ate a greater percentage of the target foods when they were labeled with fun names. Also, a larger percentage of the children tasted the foods when they were labeled with fun names. This simple strategy could be effective for increasing consumption of healthy foods among young children. PMID- 26257584 TI - Contributions of head-mounted cameras to studying the visual environments of infants and young children. AB - Head-mounted video cameras (with and without an eye camera to track gaze direction) are being increasingly used to study infants' and young children's visual environments and provide new and often unexpected insights about the visual world from a child's point of view. The challenge in using head cameras is principally conceptual and concerns the match between what these cameras measure and the research question. Head cameras record the scene in front of faces and thus answer questions about those head-centered scenes. In this "tools of the trade" article, we consider the unique contributions provided by head-centered video, the limitations and open questions that remain for head-camera methods, and the practical issues of placing head-cameras on infants and analyzing the generated video. PMID- 26257585 TI - Effect of the Materials Properties of Hydroxyapatite Nanoparticles on Fibronectin Deposition and Conformation. AB - Hydroxyapatite (HAP, Ca10(PO4)6(OH)2) nanoparticles with controlled materials properties have been synthesized through a two-step hydrothermal aging method to investigate fibronectin (Fn) adsorption. Two distinct populations of HAP nanoparticles have been generated: HAP1 particles had smaller size, plate-like shape, lower crystallinity, and more negative zeta potential than HAP2 particles. We then developed two-dimensional platforms containing HAP and Fn and analyzed both the amount and the conformation of Fn via Forster resonance energy transfer (FRET) at various HAP concentrations. Our FRET analysis reveals that larger amounts of more compact Fn molecules were adsorbed onto HAP1 than onto HAP2 particles. Additionally, our data show that the amount of compact Fn adsorbed increased with increasing HAP concentration due to the formation of nanoparticle agglomerates. We propose that both the surface chemistry of single nanoparticles and the size and morphology of HAP agglomerates play significant roles in the interaction of Fn with HAP. Collectively, our findings suggest that the HAP induced conformational changes of Fn, a critical mechanotransducer protein involved in the communication of cells with their environment, will ultimately affect downstream cellular behaviors. These results have important implications for our understanding of organic-inorganic interactions in physiological and pathological biomineralization processes such as HAP-related inflammation. PMID- 26257586 TI - A Smart Wirelessly Powered Homecage for Long-Term High-Throughput Behavioral Experiments. AB - A wirelessly powered homecage system, called the EnerCage-HC, that is equipped with multicoil wireless power transfer, closed-loop power control, optical behavioral tracking, and a graphic user interface is presented for longitudinal electrophysiology and behavioral neuroscience experiments. The EnerCage-HC system can wirelessly power a mobile unit attached to a small animal subject and also track its behavior in real-time as it is housed inside a standard homecage. The EnerCage-HC system is equipped with one central and four overlapping slanted wire wound coils with optimal geometries to form three- and four-coil power transmission links while operating at 13.56 MHz. Utilizing multicoil links increases the power transfer efficiency (PTE) compared with conventional two-coil links and also reduces the number of power amplifiers to only one, which significantly reduces the system complexity, cost, and heat dissipation. A Microsoft Kinect installed 90 cm above the homecage localizes the animal position and orientation with 1.6-cm accuracy. Moreover, a power management ASIC, including a high efficiency active rectifier and automatic coil resonance tuning, was fabricated in a 0.35-MUm 4M2P standard CMOS process for the mobile unit. The EnerCage-HC achieves a max/min PTE of 36.3%/16.1% at the nominal height of 7 cm. In vivo experiments were conducted on freely behaving rats by continuously delivering 24 mW to the mobile unit for >7 h inside a standard homecage. PMID- 26257587 TI - Regularization Paths for Conditional Logistic Regression: The clogitL1 Package. AB - We apply the cyclic coordinate descent algorithm of Friedman, Hastie, and Tibshirani (2010) to the fitting of a conditional logistic regression model with lasso [Formula: see text] and elastic net penalties. The sequential strong rules of Tibshirani, Bien, Hastie, Friedman, Taylor, Simon, and Tibshirani (2012) are also used in the algorithm and it is shown that these offer a considerable speed up over the standard coordinate descent algorithm with warm starts. Once implemented, the algorithm is used in simulation studies to compare the variable selection and prediction performance of the conditional logistic regression model against that of its unconditional (standard) counterpart. We find that the conditional model performs admirably on datasets drawn from a suitable conditional distribution, outperforming its unconditional counterpart at variable selection. The conditional model is also fit to a small real world dataset, demonstrating how we obtain regularization paths for the parameters of the model and how we apply cross validation for this method where natural unconditional prediction rules are hard to come by. PMID- 26257588 TI - The System Design and Evaluation of a 7-DOF Image-Guided Venipuncture Robot. AB - Accessing the venous bloodstream to deliver fluids or obtain a blood sample is the most common clinical routine practiced in the U.S. Practitioners continue to rely on manual venipuncture techniques, but success rates are heavily dependent on clinician skill and patient physiology. In the U.S., failure rates can be as high as 50% in difficult patients, making venipuncture the leading cause of medical injury. To improve the rate of first-stick success, we have developed a portable autonomous venipuncture device that robotically servos a needle into a suitable vein under image guidance. The device operates in real time, combining near-infrared and ultra-sound imaging, image analysis, and a 7-degree-of-freedom (DOF) robotic system to perform the venipuncture. The robot consists of a 3-DOF gantry to image the patient's peripheral forearm veins and a miniaturized 4-DOF serial arm to guide the cannula into the selected vein under closed-loop control. In this paper, we present the system architecture of the robot and evaluate the accuracy and precision through tracking, free-space positioning, and in vitro phantom cannulation experiments. The results demonstrate sub-millimeter accuracy throughout the operating workspace of the manipulator and a high rate of success when cannulating phantom veins in a skin-mimicking tissue model. PMID- 26257590 TI - Laboratory Tests Ordered By a Chiropractic Sports Physician on Elite Athletes Over a 1-Year Period. AB - OBJECTIVE: The purpose of this study is to describe and discuss laboratory tests ordered on elite athletes in an interdisciplinary sports medicine clinic by a doctor of chiropractic over 1 calendar year. METHODS: A retrospective review of laboratory tests ordered during routine clinical practice as standard screening and diagnostic tests from November 1, 2009, to November 1, 2010 was performed. Data were collected during clinical encounters at one sports medicine clinic and entered into a database for analysis. Descriptive and frequency statistics were used to describe the tests ordered and the frequency of abnormal findings. RESULTS: Five hundred and thirty-nine studies were ordered for diagnostic and routine screenings on 137 athlete patients (86 males, 51 females), representing 49 types of tests. Sample sources included blood, urine, skin lesions, and fecal matter. The most commonly ordered tests were complete blood count, comprehensive metabolic panel, serum ferritin, creatine kinase, serum iron and total iron binding capacity, total cortisol, thyroid stimulating hormone, and lipid panels. There were 217 studies (40%) flagged as abnormal by the reporting laboratory. CONCLUSION: This report provides greater insight into the diverse array of laboratory studies ordered over a 1-year period for diagnosis and screening of elite athletes. A high percentage of the results were flagged as abnormal by the laboratory. These findings show that the unique physiology of the elite athlete must be considered when interpreting laboratory findings in this population. PMID- 26257591 TI - Kienbock Disease: A Complicated Postsurgical Case Study Using Diagnostic Ultrasonography. AB - OBJECTIVE: The purpose of this case report is to describe a case of Kienbock disease (lunatomalacia) that was identified through diagnostic ultrasonography. CLINICAL FEATURES: A 27-year-old man presented to a chiropractic teaching clinic with a 3-year history of wrist pain. The history of chief concern consisted of lunatomalacia, diagnosed 2 years prior, with surgical intervention consisting of radial osteotomy and vascularized bone graft. Radiography and ultrasonography were performed upon presentation and at 2-year follow-up that demonstrated progressive collapse and fragmentation of his lunate with the development of progressive scapholunate advanced collapse of the wrist. INTERVENTION AND OUTCOME: Conservative care included class IV cold laser and a splint worn during strenuous activity and while sleeping. The patient received minimal pain relief and continued to experience chronic left wrist pain. He is continuing conservative care and evaluating options for further surgical intervention. CONCLUSION: This case demonstrates a patient with chronic wrist pain and progressive collapse of the lunate demonstrated on multiple imaging modalities after surgical intervention. To our knowledge, this is the first case demonstrating Kienbock disease using diagnostic ultrasonography. PMID- 26257592 TI - Multiple Venous Thromboses Presenting as Mechanical Low Back Pain in an 18-Year Old Woman. AB - OBJECTIVE: The purpose of this case report is to describe a patient who presented with acute musculoskeletal symptoms but was later diagnosed with multiple deep vein thrombosis (DVT). CLINICAL FEATURES: An 18-year-old female presented to a chiropractic clinic with left lumbosacral pain with referral into the posterior left thigh. A provisional diagnosis was made of acute myofascial syndrome of the left piriformis and gluteus medius muscles. The patient received 3 chiropractic treatments over 1 week resulting in 80% improvement in pain intensity. Two days later, a sudden onset of severe abdominal pain caused the patient to seek urgent medical attention. A diagnostic ultrasound of the abdomen and pelvis were performed and interpreted as normal. Following this, the patient reported increased pain in her left leg. Evaluation revealed edema of the left calf and decreased left lower limb sensation. A venous Doppler ultrasound was ordered. INTERVENTION AND OUTCOMES: Doppler ultrasound revealed reduction of the venous flow in the femoral vein area. An additional ultrasonography evaluation revealed an extensive DVTs affecting the left femoral vein and iliac axis extending towards the vena cava. Upon follow-up with a hematologist, the potential diagnosis of May-Thurner syndrome was considered based on the absence of blood dyscrasias and sustained anatomical changes found in the left common iliac vein at its junction with the right common iliac artery. A week following discharge, she presented with chest pain and was diagnosed with venous thromboembolism. The patient was successfully treated with anticoagulation therapy and insertion of a vena cava filter. CONCLUSION: Although DVTs are common in the general population, presence in low-risk individuals may be overlooked. In the presence of subtle initial clinical signs such as those described in this case report, clinicians should keep a high index of suspicion for a DVT. Rapid identification of such clinical signs in association with a lack of objective examination findings warrants further evaluation due to potentially negative outcomes. PMID- 26257593 TI - Manipulation in the Treatment of Plantar Digital Neuralgia: A Retrospective Study of 38 Cases. AB - OBJECTIVE: The purpose of this retrospective case series is to describe treatment outcomes for patients with plantar digital neuralgia (PDN) (Morton's neuroma) who were treated using foot manipulation. METHODS: Charts were reviewed retrospectively for patients with a diagnosis of PDN and who received a minimum of 6 treatments consisting of manipulation alone. Visual analogue pain scales (VAS) and pressure threshold meter readings (PTM) were extracted as outcome measures. RESULTS: Thirty-eight cases met inclusion criteria. Mean pretreatment duration of pain was 28 months. Mean pretreatment VAS was 69.5/100 mm. Mean pretreatment PTM was 2.54 Kp. By the sixth treatment, 30 (79%) of the 38 patients scored a VAS of 0 mm and a further 4 (10%) were below 10 mm. Contralateral limb PTM showed a mean pre-treatment score of 5.5 Kp, which rose slightly to 5.85 Kp. This compared to a pre-treatment score of 2.54 Kp rising to 5.86 Kp in the affected limb. This represents a 126% increase in the affected side compared to 6.5% in the unaffected limb. Statistical analysis demonstrated a significant linear trend between decreasing VAS and manipulation (P < .001). CONCLUSION: The patients with PDN who were included in this case series improved with conservative care that included only foot manipulation. PMID- 26257594 TI - WFC'S 13th Biennial Congress Proceedings Athens, Greece, 10-13, 2013: Abstracts of the Scientific Sessions. AB - The World Federation of Chiropractic (WFC) held its 13th Biennial Congress in Athens, Greece, on May 13 through 16, 2015. The WFC call for abstracts resulted in 237 submissions from 19 countries (Australia, Bahrain, Brazil, Canada, Denmark, Greece, Ireland, Italy, Republic of Korea, Mexico, Netherlands, New Zealand, Norway, South Africa, Spain, Sweden, Switzerland, United Kingdom, and the United States). From these abstracts, a total of 40 platforms and 117 posters were presented at the Congress. PMID- 26257595 TI - Urinary proteomics in chronic kidney disease: diagnosis and risk of progression beyond albuminuria. AB - BACKGROUND: The contrast between a high prevalence of chronic kidney disease (CKD) and the low incidence of end-stage renal disease highlights the need for new biomarkers of progression beyond albuminuria testing. Urinary proteomics is a promising method, but more studies focusing on progression rate and patients with hypertensive nephropathy are needed. RESULTS: We analyzed urine samples with capillary electrophoresis coupled to a mass-spectrometer from 18 well characterized patients with CKD stage 4-5 (of whom six with hypertensive nephropathy) and 17 healthy controls. Classification scores based on a previously developed panel of 273 urinary peptides were calculated and compared to urine albumin dipstick results. Urinary proteomics classified CKD with a sensitivity of 0.95 and specificity of 1.00. Overall diagnostic accuracy (area under ROC curve) was 0.98, which was better than for albuminuria (0.85, p = 0.02). Results for hypertensive nephropathy were similar to other CKD diagnoses. Adding the proteomic score to an albuminuria model improved detection of rapid kidney function decline (>4 ml/min/1.73 m(2) per year) substantially: area under ROC curve increased from 0.762 to 0.909 (p = 0.042), and 38% of rapid progressors were correctly reclassified to a higher risk and 55% of slow progressors were correctly reclassified to a lower risk category. Reduced excretion of collagen types I-III, uromodulin, and other indicators of interstitial inflammation, fibrosis and tubular dysfunction were associated with CKD diagnosis and rapid progression. Patients with hypertensive nephropathy displayed the same findings as other types of CKD. CONCLUSIONS: Urinary proteomic analyses had a high diagnostic accuracy for CKD, including hypertensive nephropathy, and strongly improved identification of patients with rapid kidney function decline beyond albuminuria testing. PMID- 26257596 TI - ASIC1A in the bed nucleus of the stria terminalis mediates TMT-evoked freezing. AB - Mice display an unconditioned freezing response to TMT, a predator odor isolated from fox feces. Here we found that in addition to freezing, TMT caused mice to decrease breathing rate, perhaps because of the aversive smell. Consistent with this possibility, olfactory bulb lesions attenuated this effect of TMT, as well as freezing. Interestingly, butyric acid, another foul odor, also caused mice to reduce breathing rate. However, unlike TMT, butyric acid did not induce freezing. Thus, although these aversive odors may affect breathing, the unpleasant smell and suppression of breathing by themselves are insufficient to cause freezing. Because the acid-sensing ion channel-1A (ASIC1A) has been previously implicated in TMT-evoked freezing, we tested whether Asic1a disruption also altered breathing. We found that TMT reduced breathing rate in both Asic1a(+/+) and Asic1a(-/-) mice, suggesting that ASIC1A is not required for TMT to inhibit breathing and that the absence of TMT-evoked freezing in the Asic1a(-/-) mice is not due to an inability to detect TMT. These observations further indicate that ASIC1A must affect TMT freezing in another way. Because the bed nucleus of the stria terminalis (BNST) has been critically implicated in TMT-evoked freezing and robustly expresses ASIC1A, we tested whether ASIC1A in the BNST plays a role in TMT-evoked freezing. We disrupted ASIC1A in the BNST of Asic1a(loxP/loxP) mice by delivering Cre recombinase to the BNST with an adeno-associated virus (AAV) vector. We found that disrupting ASIC1A in the BNST reduced TMT-evoked freezing relative to control mice in which a virus expressing eGFP was injected. To test whether ASIC1A in the BNST was sufficient to increase TMT-evoked freezing, we used another AAV vector to express ASIC1A in the BNST of Asic1a(-/-) mice. We found region-restricted expression of ASIC1A in the BNST increased TMT-elicited freezing. Together, these data suggest that the BNST is a key site of ASIC1A action in TMT-evoked freezing. PMID- 26257597 TI - Brain oscillatory activity during motor preparation: effect of directional uncertainty on beta, but not alpha, frequency band. AB - In time-constraint activities, such as sports, it is advantageous to be prepared to act even before knowing precisely what action will be needed. Here, we studied the relation between neural oscillations during motor preparation and amount of uncertainty about the direction of the upcoming target. Ten right-handed volunteers participated in a cued center-out task. A brief visual cue identified the region of space in which the target would appear. Three cue sizes were used to vary the amount of information about the direction of the upcoming target. The target appeared at a random location within the region indicated by the cue, and the participants moved a joystick-controlled cursor toward it. Time-frequency analyses showed phasic increases of power in low (delta/theta: <7 Hz) and high (gamma: >30 Hz) frequency-bands in relation to the onset of visual stimuli and of the motor response. More importantly in regard to motor preparation, there was a tonic reduction of power in the alpha (8-12 Hz) and beta (14-30 Hz) bands during the period between cue presentation and target onset. During motor preparation, the main source of change of power of the alpha band was localized over the contralateral sensorimotor region and both parietal cortices, whereas for the beta-band the main source was the contralateral sensorimotor region. During cue presentation, the reduction of power of the alpha-band in the occipital lobe showed a brief differentiation of condition: the wider the visual cue, the more the power of the alpha-band decreased. However, during motor preparation, only the power of the beta-band was dependent on directional uncertainty: the less the directional uncertainty, the more the power of the beta-band decreased. In conclusion, the results indicate that the power in the alpha-band is associated briefly with cue size, but is otherwise an undifferentiated indication of neural activation, whereas the power of the beta-band reflects the level of motor preparation. PMID- 26257598 TI - Antidepressant mechanism of ketamine: perspective from preclinical studies. AB - A debilitating mental disorder, major depressive disorder is a leading cause of global disease burden. Existing antidepressant drugs are not adequate for the majority of depressed patients, and large clinical studies have demonstrated their limited efficacy and slow response onset. Growing evidence of low-dose ketamine's rapid and potent antidepressant effects offers strong potential for future antidepressant agents. However, ketamine has considerable drawbacks such as its abuse potential, psychomimetic effects, and increased oxidative stress in the brain, thus limiting its widespread clinical use. To develop superior antidepressant drugs, it is crucial to better understand ketamine's antidepressant mechanism of action. Recent preclinical studies indicate that ketamine's antidepressant mechanism involves mammalian target of rapamycin pathway activation and subsequent synaptogenesis in the prefrontal cortex, as well as glycogen synthase kinase-3 beta (GSK-3beta) inactivation. Adjunct GSK 3beta inhibitors, such as lithium, can enhance ketamine's efficacy by augmenting and prolonging its antidepressant effects. Given the potential for depressive relapses, lithium in addition to ketamine is a promising solution for this clinical issue. PMID- 26257599 TI - Modulation of incentivized dishonesty by disgust facial expressions. AB - Disgust modulates moral decisions involving harming others. We recently specified that this effect is bi-directionally modulated by individual sensitivity to disgust. Here, we show that this effect generalizes to the moral domain of honesty and extends to outcomes with real-world impact. We employed a dice rolling task in which participants were incentivized to dishonestly report outcomes to increase their potential final monetary payoff. Disgust or control facial expressions were presented subliminally on each trial. Our results reveal that the disgust facial expressions altered honest reporting as a bi-directional function moderated by individual sensitivity. Combining these data with those from prior experiments revealed that the effect of disgust presentation on both harm judgments and honesty could be accounted for by the same bidirectional function, with no significant effect of domain. This clearly demonstrates that disgust facial expressions produce the same modulation of moral judgments across different moral foundations (harm and honesty). Our results suggest strong overlap in the cognitive/neural processes of moral judgments across moral foundations, and provide a framework for further studies to specify the integration of emotional information in moral decision making. PMID- 26257600 TI - Cortical iron regulation and inflammatory response in Alzheimer's disease and APPSWE/PS1DeltaE9 mice: a histological perspective. AB - Disruption of iron homeostasis and increased glial response are known to occur in brains afflicted by Alzheimer's disease (AD). While the APP/PS1 transgenic mouse model recapitulates the hallmark amyloid-beta plaque pathology of AD, it does so in a different neuronal mileu than humans. Understanding the iron characteristics and glial response of the APP/PS1 model is important when testing new treatment procedures and translating these results. Brain tissue from AD patients, APP/PS1 mice, and controls were stained for iron, H- and L-ferritin, microglia, astrocytes, Abeta40/42, and degenerating neurons. The histological data demonstrate differences in ferritin, iron distribution, gliosis, and Abeta plaque composition between APP/PS1 and AD tissue. Specifically, an association between focal iron deposition and Abeta plaques is found ubiquitously throughout the AD tissue and is not observed in the APP/PS1 mouse model. Ferritin, microglia, and astrocyte staining show differential response patterns to amyloid plaques in AD and the APP/PS1 tissue. Abeta 40 and 42 antibody and thioflavin staining demonstrate morphological differences in plaque composition. The histological data support the hypothesis that iron distribution, iron management, and glial response histologically differ between the APP/PS1 and AD brain. Acknowledging the caveat that there are distinct plaque, iron, and glial contrasts between the AD brain and the APP/PS1 mouse is crucial when utilizing this model. PMID- 26257601 TI - Boosting brain connectome classification accuracy in Alzheimer's disease using higher-order singular value decomposition. AB - Alzheimer's disease (AD) is a progressive brain disease. Accurate detection of AD and its prodromal stage, mild cognitive impairment (MCI), are crucial. There is also a growing interest in identifying brain imaging biomarkers that help to automatically differentiate stages of Alzheimer's disease. Here, we focused on brain structural networks computed from diffusion MRI and proposed a new feature extraction and classification framework based on higher order singular value decomposition and sparse logistic regression. In tests on publicly available data from the Alzheimer's Disease Neuroimaging Initiative, our proposed framework showed promise in detecting brain network differences that help in classifying different stages of Alzheimer's disease. PMID- 26257602 TI - An Importin Code in neuronal transport from synapse-to-nucleus? PMID- 26257603 TI - Investigating neuronal function with optically controllable proteins. AB - In the nervous system, protein activities are highly regulated in space and time. This regulation allows for fine modulation of neuronal structure and function during development and adaptive responses. For example, neurite extension and synaptogenesis both involve localized and transient activation of cytoskeletal and signaling proteins, allowing changes in microarchitecture to occur rapidly and in a localized manner. To investigate the role of specific protein regulation events in these processes, methods to optically control the activity of specific proteins have been developed. In this review, we focus on how photosensory domains enable optical control over protein activity and have been used in neuroscience applications. These tools have demonstrated versatility in controlling various proteins and thereby cellular functions, and possess enormous potential for future applications in nervous systems. Just as optogenetic control of neuronal firing using opsins has changed how we investigate the function of cellular circuits in vivo, optical control may yet yield another revolution in how we study the circuitry of intracellular signaling in the brain. PMID- 26257604 TI - On the possible role of protein vibrations in information processing in the brain: three Russian dolls. AB - Until recently it was held that the neurocomputations conducted by the brain involved only whole neurons as the operating units. This may however represent only a part of the mechanism. This theoretical and academic position article reviews the considerable evidence that allosteric interactions between proteins (as extensively described by Fuxe et al., 2014), and in particular protein vibrations in neurons, form small scale codes that are involved as parts of the complex information processing systems of the brain. The argument is then developed to suggest that the protein allosteric and vibration codes (that operate at the molecular level) are nested within a medium scale coding system whose computational units are organelles (such as microtubules). This medium scale code is nested in turn inside a large scale coding system, whose computational units are individual neurons. The hypothesis suggests that these three levels interact vertically in both directions thus materially increasing the computational capacity of the brain. The whole hierarchy is thus similar to three nested Russian dolls. This theoretical development may be of use in the design of experiments to test it. PMID- 26257605 TI - The presence of cortical neurons in striatal-cortical co-cultures alters the effects of dopamine and BDNF on medium spiny neuron dendritic development. AB - Medium spiny neurons (MSNs) are the major striatal neuron and receive synaptic input from both glutamatergic and dopaminergic afferents. These synapses are made on MSN dendritic spines, which undergo density and morphology changes in association with numerous disease and experience-dependent states. Despite wide interest in the structure and function of mature MSNs, relatively little is known about MSN development. Furthermore, most in vitro studies of MSN development have been done in simple striatal cultures that lack any type of non-autologous synaptic input, leaving open the question of how MSN development is affected by a complex environment that includes other types of neurons, glia, and accompanying secreted and cell-associated cues. Here we characterize the development of MSNs in striatal-cortical co-culture, including quantitative morphological analysis of dendritic arborization and spine development, describing progressive changes in density and morphology of developing spines. Overall, MSN growth is much more robust in the striatal-cortical co-culture compared to striatal mono-culture. Inclusion of dopamine (DA) in the co-culture further enhances MSN dendritic arborization and spine density, but the effects of DA on dendritic branching are only significant at later times in development. In contrast, exogenous Brain Derived Neurotrophic Factor (BDNF) has only a minimal effect on MSN development in the co-culture, but significantly enhances MSN dendritic arborization in striatal mono-culture. Importantly, inhibition of NMDA receptors in the co culture significantly enhances the effect of exogenous BDNF, suggesting that the efficacy of BDNF depends on the cellular environment. Combined, these studies identify specific periods of MSN development that may be particularly sensitive to perturbation by external factors and demonstrate the importance of studying MSN development in a complex signaling environment. PMID- 26257606 TI - A commentary on: "Anti-muscarinic adjunct therapy accelerates functional human oligodendrocyte repair". PMID- 26257607 TI - A frequency-dependent decoding mechanism for axonal length sensing. AB - We have recently developed a mathematical model of axonal length sensing in which a system of delay differential equations describe a chemical signaling network. We showed that chemical oscillations emerge due to delayed negative feedback via a Hopf bifurcation, resulting in a frequency that is a monotonically decreasing function of axonal length. In this paper, we explore how frequency-encoding of axonal length can be decoded by a frequency-modulated gene network. If the protein output were thresholded, then this could provide a mechanism for axonal length control. We analyze the robustness of such a mechanism in the presence of intrinsic noise due to finite copy numbers within the gene network. PMID- 26257609 TI - A three-dimensional image processing program for accurate, rapid, and semi automated segmentation of neuronal somata with dense neurite outgrowth. AB - Three-dimensional (3-D) image analysis techniques provide a powerful means to rapidly and accurately assess complex morphological and functional interactions between neural cells. Current software-based identification methods of neural cells generally fall into two applications: (1) segmentation of cell nuclei in high-density constructs or (2) tracing of cell neurites in single cell investigations. We have developed novel methodologies to permit the systematic identification of populations of neuronal somata possessing rich morphological detail and dense neurite arborization throughout thick tissue or 3-D in vitro constructs. The image analysis incorporates several novel automated features for the discrimination of neurites and somata by initially classifying features in 2 D and merging these classifications into 3-D objects; the 3-D reconstructions automatically identify and adjust for over and under segmentation errors. Additionally, the platform provides for software-assisted error corrections to further minimize error. These features attain very accurate cell boundary identifications to handle a wide range of morphological complexities. We validated these tools using confocal z-stacks from thick 3-D neural constructs where neuronal somata had varying degrees of neurite arborization and complexity, achieving an accuracy of >=95%. We demonstrated the robustness of these algorithms in a more complex arena through the automated segmentation of neural cells in ex vivo brain slices. These novel methods surpass previous techniques by improving the robustness and accuracy by: (1) the ability to process neurites and somata, (2) bidirectional segmentation correction, and (3) validation via software-assisted user input. This 3-D image analysis platform provides valuable tools for the unbiased analysis of neural tissue or tissue surrogates within a 3 D context, appropriate for the study of multi-dimensional cell-cell and cell extracellular matrix interactions. PMID- 26257608 TI - Sensory and spinal inhibitory dorsal midline crossing is independent of Robo3. AB - Commissural neurons project across the midline at all levels of the central nervous system (CNS), providing bilateral communication critical for the coordination of motor activity and sensory perception. Midline crossing at the spinal ventral midline has been extensively studied and has revealed that multiple developmental lineages contribute to this commissural neuron population. Ventral midline crossing occurs in a manner dependent on Robo3 regulation of Robo/Slit signaling and the ventral commissure is absent in the spinal cord and hindbrain of Robo3 mutants. Midline crossing in the spinal cord is not limited to the ventral midline, however. While prior anatomical studies provide evidence that commissural axons also cross the midline dorsally, little is known of the genetic and molecular properties of dorsally-crossing neurons or of the mechanisms that regulate dorsal midline crossing. In this study, we describe a commissural neuron population that crosses the spinal dorsal midline during the last quarter of embryogenesis in discrete fiber bundles present throughout the rostrocaudal extent of the spinal cord. Using immunohistochemistry, neurotracing, and mouse genetics, we show that this commissural neuron population includes spinal inhibitory neurons and sensory nociceptors. While the floor plate and roof plate are dispensable for dorsal midline crossing, we show that this population depends on Robo/Slit signaling yet crosses the dorsal midline in a Robo3 independent manner. The dorsally-crossing commissural neuron population we describe suggests a substrate circuitry for pain processing in the dorsal spinal cord. PMID- 26257610 TI - Dopamine in the auditory brainstem and midbrain: co-localization with amino acid neurotransmitters and gene expression following cochlear trauma. AB - Dopamine (DA) modulates the effects of amino acid neurotransmitters (AANs), including GABA and glutamate, in motor, visual, olfactory, and reward systems (Hnasko et al., 2010; Stuber et al., 2010; Hnasko and Edwards, 2012). The results suggest that DA may play a similar modulatory role in the auditory pathways. Previous studies have shown that deafness results in decreased GABA release, changes in excitatory neurotransmitter levels, and increased spontaneous neuronal activity within brainstem regions related to auditory function. Modulation of the expression and localization of tyrosine hydroxylase (TH; the rate limiting enzyme in the production of DA) in the IC following cochlear trauma has been previously reported (Tong et al., 2005). In the current study the possibility of co localization of TH with AANs was examined. Changes in the gene expression of TH were compared with changes in the gene expression of markers for AANs in the cochlear nucleus (CN) and inferior colliculus (IC) to determine whether those deafness related changes occur concurrently. The results indicate that bilateral cochlear ablation significantly reduced TH gene expression in the CN after 2 months while in the IC the reduction in TH was observed at both 3 days and 2 months following ablation. Furthermore, in the CN, glycine transporter 2 (GLYT2) and the GABA transporter (GABAtp) were also significantly reduced only after 2 months. However, in the IC, DA receptor 1 (DRDA1), vesicular glutamate transporters 2 and 3 (VGLUT2, VGLUT3), GABAtp and GAD67 were reduced in expression both at the 3 days and 2 months time points. A close relationship between the distribution of TH and several of the AANs was determined in both the CN and the IC. In addition, GLYT2 and VGLUT3 each co-localized with TH within IC somata and dendrites. Therefore, the results of the current study suggest that DA is spatially well positioned to influence the effects of AANs on auditory neurons. PMID- 26257611 TI - Transmitter inputs to different motoneuron subgroups in the oculomotor and trochlear nucleus in monkey. AB - In all vertebrates the eyes are moved by six pairs of extraocular muscles enabling horizontal, vertical and rotatory movements. Recent work showed that each extraocular muscle is controlled by two motoneuronal groups: (1) Motoneurons of singly-innervated muscle fibers (SIF) that lie within the boundaries of motonuclei mediating a fast muscle contraction; and (2) motoneurons of multiply innervated muscle fibers (MIF) in the periphery of motonuclei mediating a tonic muscle contraction. Currently only limited data about the transmitter inputs to the SIF and MIF motoneurons are available. Here we performed a quantitative study on the transmitter inputs to SIF and MIF motoneurons of individual muscles in the oculomotor and trochlear nucleus in monkey. Pre-labeled motoneurons were immunostained for GABA, glutamate decarboxylase, GABA-A receptor, glycine transporter 2, glycine receptor 1, and vesicular glutamate transporters 1 and 2. The main findings were: (1) the inhibitory control of SIF motoneurons for horizontal and vertical eye movements differs. Unlike in previous primate studies a considerable GABAergic input was found to all SIF motoneuronal groups, whereas a glycinergic input was confined to motoneurons of the medial rectus (MR) muscle mediating horizontal eye movements and to those of the levator palpebrae (LP) muscle elevating the upper eyelid. Whereas SIF and MIF motoneurons of individual eye muscles do not differ numerically in their GABAergic, glycinergic and vGlut2 input, vGlut1 containing terminals densely covered the supraoculomotor area (SOA) targeting MR MIF motoneurons. It is reasonable to assume that the vGlut1 input affects the near response system in the SOA, which houses the preganglionic neurons mediating pupillary constriction and accommodation and the MR MIF motoneurones involved in vergence. PMID- 26257612 TI - Histological validation of high-resolution DTI in human post mortem tissue. AB - Diffusion tensor imaging (DTI) is amongst the simplest mathematical models available for diffusion magnetic resonance imaging, yet still by far the most used one. Despite the success of DTI as an imaging tool for white matter fibers, its anatomical underpinnings on a microstructural basis remain unclear. In this study, we used 65 myelin-stained sections of human premotor cortex to validate modeled fiber orientations and oft used microstructure-sensitive scalar measures of DTI on the level of individual voxels. We performed this validation on high spatial resolution diffusion MRI acquisitions investigating both white and gray matter. We found a very good agreement between DTI and myelin orientations with the majority of voxels showing angular differences less than 10 degrees . The agreement was strongest in white matter, particularly in unidirectional fiber pathways. In gray matter, the agreement was good in the deeper layers highlighting radial fiber directions even at lower fractional anisotropy (FA) compared to white matter. This result has potentially important implications for tractography algorithms applied to high resolution diffusion MRI data if the aim is to move across the gray/white matter boundary. We found strong relationships between myelin microstructure and DTI-based microstructure-sensitive measures. High FA values were linked to high myelin density and a sharply tuned histological orientation profile. Conversely, high values of mean diffusivity (MD) were linked to bimodal or diffuse orientation distributions and low myelin density. At high spatial resolution, DTI-based measures can be highly sensitive to white and gray matter microstructure despite being relatively unspecific to concrete microarchitectural aspects. PMID- 26257613 TI - High frequency synchrony in the cerebellar cortex during goal directed movements. AB - The cerebellum is involved in sensory-motor integration and cognitive functions. The origin and function of the field potential oscillations in the cerebellum, especially in the high frequencies, have not been explored sufficiently. The primary objective of this study was to investigate the spatio-temporal characteristics of high frequency field potentials (150-350 Hz) in the cerebellar cortex in a behavioral context. To this end, we recorded from the paramedian lobule in rats using micro electro-corticogram (MU-ECoG) electrode arrays while the animal performed a lever press task using the forelimb. The phase synchrony analysis shows that the high frequency oscillations recorded at multiple points across the paramedian cortex episodically synchronize immediately before and desynchronize during the lever press. The electrode contacts were grouped according to their temporal course of phase synchrony around the time of lever press. Contact groups presented patches with slightly stronger synchrony values in the medio-lateral direction, and did not appear to form parasagittal zones. The size and location of these patches on the cortical surface are in agreement with the sensory evoked granular layer patches originally reported by Welker's lab (Shambes et al., 1978). Spatiotemporal synchrony of high frequency field potentials has not been reported at such large-scales previously in the cerebellar cortex. PMID- 26257614 TI - Editorial: General anesthesia: from theory to experiments. PMID- 26257615 TI - Information asymmetry and deception. AB - Situations such as an entrepreneur overstating a project's value, or a superior choosing to under or overstate the gains from a project to a subordinate are common and may result in acts of deception. In this paper we modify the standard investment game in the economics literature to study the nature of deception. In this game a trustor (investor) can send a given amount of money to a trustee (or investee). The amount received is multiplied by a certain amount, k, and the investee then decides on how to divide the total amount received. In our modified game the information on the multiplier, k, is known only to the investee and she can send a non-binding message to the investor regarding its value. We find that 66% of the investees send false messages with both under and over, statement being observed. Investors are naive and almost half of them believe the message received. We find greater lying when the distribution of the multiplier is unknown by the investors than when they know the distribution. Further, messages make beliefs about the multiplier more pessimistic when the investors know the distribution of the multiplier, while the opposite is true when they do not know the distribution. PMID- 26257616 TI - The influence of trial order on learning from reward vs. punishment in a probabilistic categorization task: experimental and computational analyses. AB - Previous research has shown that trial ordering affects cognitive performance, but this has not been tested using category-learning tasks that differentiate learning from reward and punishment. Here, we tested two groups of healthy young adults using a probabilistic category learning task of reward and punishment in which there are two types of trials (reward, punishment) and three possible outcomes: (1) positive feedback for correct responses in reward trials; (2) negative feedback for incorrect responses in punishment trials; and (3) no feedback for incorrect answers in reward trials and correct answers in punishment trials. Hence, trials without feedback are ambiguous, and may represent either successful avoidance of punishment or failure to obtain reward. In Experiment 1, the first group of subjects received an intermixed task in which reward and punishment trials were presented in the same block, as a standard baseline task. In Experiment 2, a second group completed the separated task, in which reward and punishment trials were presented in separate blocks. Additionally, in order to understand the mechanisms underlying performance in the experimental conditions, we fit individual data using a Q-learning model. Results from Experiment 1 show that subjects who completed the intermixed task paradoxically valued the no feedback outcome as a reinforcer when it occurred on reinforcement-based trials, and as a punisher when it occurred on punishment-based trials. This is supported by patterns of empirical responding, where subjects showed more win-stay behavior following an explicit reward than following an omission of punishment, and more lose-shift behavior following an explicit punisher than following an omission of reward. In Experiment 2, results showed similar performance whether subjects received reward-based or punishment-based trials first. However, when the Q learning model was applied to these data, there were differences between subjects in the reward-first and punishment-first conditions on the relative weighting of neutral feedback. Specifically, early training on reward-based trials led to omission of reward being treated as similar to punishment, but prior training on punishment-based trials led to omission of reward being treated more neutrally. This suggests that early training on one type of trials, specifically reward based trials, can create a bias in how neutral feedback is processed, relative to those receiving early punishment-based training or training that mixes positive and negative outcomes. PMID- 26257617 TI - Conditioned place preference successfully established in typically developing children. AB - Affective processing, known to influence attention, motivation, and emotional regulation is poorly understood in young children, especially for those with neurodevelopmental disorders characterized by language impairments. Here we faithfully adapt a well-established animal paradigm used for affective processing, conditioned place preference (CPP) for use in typically developing children between the ages of 30-55 months. Children displayed a CPP, with an average 2.4 fold increase in time spent in the preferred room. Importantly, associative learning as assessed with CPP was not correlated with scores on the Mullen Scales of Early Learning (MSEL), indicating that CPP can be used with children with a wide range of cognitive skills. PMID- 26257618 TI - Avoidance learning: a review of theoretical models and recent developments. AB - Avoidance is a key characteristic of adaptive and maladaptive fear. Here, we review past and contemporary theories of avoidance learning. Based on the theories, experimental findings and clinical observations reviewed, we distill key principles of how adaptive and maladaptive avoidance behavior is acquired and maintained. We highlight clinical implications of avoidance learning theories and describe intervention strategies that could reduce maladaptive avoidance and prevent its return. We end with a brief overview of recent developments and avenues for further research. PMID- 26257619 TI - Intergenerational transmission of alloparental behavior and oxytocin and vasopressin receptor distribution in the prairie vole. AB - Variation in the early environment has the potential to permanently alter offspring behavior and development. We have previously shown that naturally occurring variation in biparental care of offspring in the prairie vole is related to differences in social behavior of the offspring. It was not, however, clear whether the behavioral differences seen between offspring receiving high compared to low amounts of parental care were the result of different care experiences or were due to shared genetics with their high-contact or low-contact parents. Here we use cross-fostering methods to determine the mode of transmission of alloparental behavior and oxytocin receptor (OTR) and vasopressin V1a receptor (V1aR) binding from parent to offspring. Offspring were cross fostered or in-fostered on postnatal day 1 and parental care received was quantified in the first week postpartum. At weaning, offspring underwent an alloparental care test and brains were then collected from all parents and offspring to examine OTR and V1aR binding. Results indicate that alloparental behavior of offspring was predicted by the parental behavior of their rearing parents. Receptor binding for both OTR and V1aR tended to be predicted by the genetic mothers for female offspring and by the genetic fathers for male offspring. These findings suggest a different, sex-dependent, role of early experience and genetics in shaping behavior compared to receptor distribution and support the notion of sex-dependent outcomes. PMID- 26257620 TI - Short-term effects of prosocial video games on aggression: an event-related potential study. AB - Previous research has shown that exposure to violent video games increases aggression, whereas exposure to prosocial video games can reduce aggressive behavior. However, little is known about the neural correlates of these behavioral effects. This work is the first to investigate the electrophysiological features of the relationship between playing a prosocial video game and inhibition of aggressive behavior. Forty-nine subjects played either a prosocial or a neutral video game for 20 min, then participated in an event-related potential (ERP) experiment based on an oddball paradigm and designed to test electrophysiological responses to prosocial and violent words. Finally, subjects completed a competitive reaction time task (CRTT) which based on Taylor's Aggression Paradigm and contains reaction time and noise intensity chosen as a measure of aggressive behavior. The results show that the prosocial video game group (compared to the neutral video game group) displayed smaller P300 amplitudes, were more accurate in distinguishing violent words, and were less aggressive as evaluated by the CRTT of noise intensity chosen. A mediation analysis shows that the P300 amplitude evoked by violent words partially mediates the relationship between type of video game and subsequent aggressive behavior. The results support theories based on the General Learning Model. We provide converging behavioral and neural evidence that exposure to prosocial media may reduce aggression. PMID- 26257621 TI - Wired for motherhood: induction of maternal care but not maternal aggression in virgin female CD1 mice. AB - Virgin adult female mice display nearly spontaneous maternal care towards foster pups after a short period of sensitization. This indicates that maternal care is triggered by sensory stimulation provided by the pups and that its onset is largely independent on the physiological events related to gestation, parturition and lactation. Conversely, the factors influencing maternal aggression are poorly understood. In this study, we sought to characterize two models of maternal sensitization in the outbred CD1 strain. To do so, a group of virgin females (godmothers) were exposed to continuous cohabitation with a lactating dam and their pups from the moment of parturition, whereas a second group (pup-sensitized females), were exposed 2 h daily to foster pups. Both groups were tested for maternal behavior on postnatal days 2-4. Godmothers expressed full maternal care from the first test. Also, they expressed higher levels of crouching than dams. Pup-sensitized females differed from dams in all measures of pup-directed behavior in the first test, and expressed full maternal care after two sessions of contact with pups. However, both protocols failed to induce maternal aggression toward a male intruder after full onset of pup-directed maternal behavior, even in the presence of pups. Our study confirms that adult female mice need a short sensitization period before the onset of maternal care. Further, it shows that pup-oriented and non-pup-oriented components of maternal behavior are under different physiological control. We conclude that the godmother model might be useful to study the physiological and neural bases of the maternal behavior repertoire. PMID- 26257622 TI - Multi-scale complexity analysis of muscle coactivation during gait in children with cerebral palsy. AB - The objective of this study is to characterize complexity of lower-extremity muscle coactivation and coordination during gait in children with cerebral palsy (CP), children with typical development (TD) and healthy adults, by applying recently developed multivariate multi-scale entropy (MMSE) analysis to surface electromyographic (EMG) signals. Eleven CP children (CP group), eight TD children and seven healthy adults (considered as an entire control group) were asked to walk while surface EMG signals were collected from five thigh muscles and three lower leg muscles on each leg (16 EMG channels in total). The 16-channel surface EMG data, recorded during a series of consecutive gait cycles, were simultaneously processed by multivariate empirical mode decomposition (MEMD), to generate fully aligned data scales for subsequent MMSE analysis. In order to conduct extensive examination of muscle coactivation complexity using the MEMD enhanced MMSE, 14 data analysis schemes were designed by varying partial muscle combinations and time durations of data segments. Both TD children and healthy adults showed almost consistent MMSE curves over multiple scales for all the 14 schemes, without any significant difference (p > 0.09). However, distinct diversity in MMSE curve was observed in the CP group when compared with the control group. There appears to be diverse neuropathological processes in CP that may affect dynamical complexity of muscle coactivation and coordination during gait. The abnormal complexity patterns emerging in the CP group can be attributed to different factors such as motor control impairments, loss of muscle couplings, and spasticity or paralysis in individual muscles. This study expands our knowledge of neuropathology of CP from a novel point of view of muscle co activation complexity, which might be useful to derive a quantitative index for assessing muscle activation characteristics as well as motor function in CP. PMID- 26257623 TI - Recovery of post stroke proximal arm function, driven by complex neuroplastic bilateral brain activation patterns and predicted by baseline motor dysfunction severity. AB - OBJECTIVES: Neuroplastic changes that drive recovery of shoulder/elbow function after stroke have been poorly understood. The purpose of this study was to determine the relationship between neuroplastic brain changes related to shoulder/elbow movement control in response to treatment and recovery of arm motor function in chronic stroke survivors. METHODS: Twenty-three chronic stroke survivors were treated with 12 weeks of arm rehabilitation. Outcome measures included functional Magnetic Resonance Imaging (fMRI) for the shoulder/elbow components of reach and a skilled motor function test (Arm Motor Abilities Test, AMAT), collected before and after treatment. RESULTS: We observed two patterns of neuroplastic changes that were associated with gains in motor function: decreased or increased task-related brain activation. Those with significantly better motor function at baseline exhibited a decrease in brain activation in response to treatment, evident in the ipsilesional primary motor and contralesional supplementary motor regions; in contrast, those with greater baseline motor impairment, exhibited increased brain activation in response to treatment. There was a linear relationship between greater functional gain (AMAT) and increased activation in bilateral primary motor, contralesional primary and secondary sensory regions, and contralesional lateral premotor area, after adjusting for baseline AMAT, age, and time since stroke. CONCLUSIONS: Recovery of functional reach involves recruitment of several contralesional and bilateral primary motor regions. In response to intensive therapy, the direction of functional brain change (i.e., increase or decrease in task-related brain recruitment) for shoulder/elbow reach components depends on baseline level of motor function and may represent either different phases of recovery or different patterns of neuroplasticity that drive functional recovery. PMID- 26257624 TI - Time course of EEG oscillations during repeated listening of a well-known aria. AB - While previous studies have analyzed mean neurophysiological responses to musical stimuli, the current study aimed to identify specific time courses of electroencephalography (EEG) oscillations, which are associated with dynamic changes in the acoustic features of the musical stimulus. In addition, we were interested in whether these time courses change during a repeated presentation of the same musical piece. A total of 16 subjects repeatedly listened to the well known aria "Nessun dorma," sung by Paul Potts, while continuous 128-channel EEG and heart rate, as well as electrodermal responses, were recorded. The time courses for the EEG oscillations were calculated using a time resolution of 1 second for several frequency bands, on the basis of individual alpha-peak frequencies (theta, low alpha-1, low alpha-2, upper alpha, and beta). For all frequency bands, we identified a more or less continuous increase in power relative to a baseline period, indicating strong event-related synchronization (ERS) during music listening. The ERS time courses, however, did not correlate strongly with the time courses of the acoustic features of the aria. In addition, we did not observe changes in EEG oscillations after repeated presentation of the same musical piece. Aside from this distinctive feature, we identified a remarkable variability in EEG oscillations, both within and between the repeated presentations of the aria. We interpret the continuous increase in ERS observed in all frequency bands during music listening as an indicator of a particular neurophysiological and psychological state evoked by music listening. We suggest that this state is characterized by increased internal attention (accompanied by reduced external attention), increased inhibition of brain networks not involved in the generation of this internal state, the maintenance of a particular level of general alertness, and a type of brain state that can be described as "mind wandering." The overall state can be categorized as a psychological process that may be seen as a "drawing in" to the musical piece. However, this state is not stable and varies considerably throughout the music listening session and across subjects. Most important, however, is the finding that the neurophysiological activations occurring during music listening are dynamic and not stationary. PMID- 26257625 TI - The pleasures of sad music: a systematic review. AB - Sadness is generally seen as a negative emotion, a response to distressing and adverse situations. In an aesthetic context, however, sadness is often associated with some degree of pleasure, as suggested by the ubiquity and popularity, throughout history, of music, plays, films and paintings with a sad content. Here, we focus on the fact that music regarded as sad is often experienced as pleasurable. Compared to other art forms, music has an exceptional ability to evoke a wide-range of feelings and is especially beguiling when it deals with grief and sorrow. Why is it, then, that while human survival depends on preventing painful experiences, mental pain often turns out to be explicitly sought through music? In this article we consider why and how sad music can become pleasurable. We offer a framework to account for how listening to sad music can lead to positive feelings, contending that this effect hinges on correcting an ongoing homeostatic imbalance. Sadness evoked by music is found pleasurable: (1) when it is perceived as non-threatening; (2) when it is aesthetically pleasing; and (3) when it produces psychological benefits such as mood regulation, and empathic feelings, caused, for example, by recollection of and reflection on past events. We also review neuroimaging studies related to music and emotion and focus on those that deal with sadness. Further exploration of the neural mechanisms through which stimuli that usually produce sadness can induce a positive affective state could help the development of effective therapies for disorders such as depression, in which the ability to experience pleasure is attenuated. PMID- 26257626 TI - Space distribution of EEG responses to hanoi-moving visual and auditory stimulation with Fourier Independent Component Analysis. AB - BACKGROUND AND OBJECTIVE: The relationship between EEG source signals and action related visual and auditory stimulation is still not well-understood. The objective of this study was to identify EEG source signals and their associated action-related visual and auditory responses, especially independent components of EEG. METHODS: A hand-moving-Hanoi video paradigm was used to study neural correlates of the action-related visual and auditory information processing determined by mu rhythm (8-12 Hz) in 16 healthy young subjects. Independent component analysis (ICA) was applied to identify separate EEG sources, and further computed in the frequency domain by applying-Fourier transform ICA (F ICA). RESULTS: F-ICA found more sensory stimuli-related independent components located within the sensorimotor region than ICA did. The total number of independent components of interest from F-ICA was 768, twice that of 384 from traditional time-domain ICA (p < 0.05). In the sensory-motor region C3 or C4, the total source signals intensity distribution values from all 14 subjects was 23.00 (Mean 1.64 +/- 1.17) from F-ICA; which was more than the 10.5 (Mean 0.75 +/- 0.62) from traditional time-domain ICA (p < 0.05). Furthermore, the intensity distribution of source signals in the C3 or C4 region was statistically significant between the ICA and F-ICA groups (strong 50 vs. 92%; weak 50 vs. 8% retrospectively; p < 0.05). In the Pz region, the total source signal intensity distribution from F-ICA was 12.50 (Mean 0.89 +/- 0.53); although exceeding that of traditional time-domain ICA 8.20 (Mean 0.59 +/- 0.48), the difference was not statistically significant (p > 0.05). CONCLUSIONS: These results support the hypothesis that mu rhythm was sensitive to detection of the cognitive expression, which could be reflected by the function in the parietal lobe sensory-motor region. The results of this study could potentially be applied into early diagnosis for those with visual and hearing impairments in the near future. PMID- 26257627 TI - Corrigendum: The development of trunk control and its relation to reaching in infancy: a longitudinal study. AB - [This corrects the article on p. 94 in vol. 9, PMID: 25759646.]. PMID- 26257628 TI - Linking inter-individual differences in the perceptual load effect to spontaneous brain activity. AB - Previous researches have widely demonstrated that the interference from peripheral distractor will decrease when the task load is high. However, no study to date has paid attention to the individual differences in perceptual load effect (PLE) and little is known of spontaneous brain activity associated with PLE during resting state. To investigate this issue, we used resting-state functional Magnetic Resonance Imaging (fMRI) to examine the relationship between the amplitude of low-frequency fluctuations (ALFFs) and PLE. The results showed that there were large individual differences in PLE and we found PLE was significantly associated with ALFFs in left inferior temporal gyrus (ITG) and left precentral/postcentral gyrus. The present study suggested that the PLE was measurable, and there were individual differences in this effect. Moreover, these results implicated that: 1) mutual competition for limited capacity, which is involved in visual attention, and 2) response control that is included in behavior response both may contribute to the modulation induced by perceptual load. PMID- 26257630 TI - Corrigendum: Society, Organizations and the Brain: Building toward a Unified Cognitive Neuroscience Perspective. AB - [This corrects the article on p. 289 in vol. 9, PMID: 26042022.]. PMID- 26257629 TI - Neuroart: picturing the neuroscience of intentional actions in art and science. AB - Intentional actions cover a broad spectrum of human behaviors involving consciousness, creativity, innovative thinking, problem-solving, critical thinking, and other related cognitive processes self-evident in the arts and sciences. The author discusses the brain activity associated with action intentions, connecting this activity with the creative process. Focusing on one seminal artwork created and exhibited over a period of three decades, Thought Assemblies (1979-82, 2014), he describes how this symbolic art interprets the neuropsychological processes of intuition and analytical reasoning. It explores numerous basic questions concerning observed interactions between artistic and scientific inquiries, conceptions, perceptions, and representations connecting mind and nature. Pointing to some key neural mechanisms responsible for forming and implementing intentions, he considers why and how we create, discover, invent, and innovate. He suggests ways of metaphorical thinking and symbolic modeling that can help integrate the neuroscience of intentional actions with the neuroscience of creativity, art and neuroaesthetics. PMID- 26257631 TI - Corrigendum: A comparison of two sleep spindle detection methods based on all night averages: individually adjusted vs. fixed frequencies. AB - [This corrects the article on p. 52 in vol. 9, PMID: 25741264.]. PMID- 26257632 TI - A systematic review of non-motor rTMS induced motor cortex plasticity. AB - Motor cortex excitability can be measured by single- and paired-pulse transcranial magnetic stimulation (TMS). Repetitive transcranial magnetic stimulation (rTMS) can induce neuroplastic effects in stimulated and in functionally connected cortical regions. Due to its ability to non-invasively modulate cortical activity, rTMS has been investigated for the treatment of various neurological and psychiatric disorders. However, such studies revealed a high variability of both clinical and neuronal effects induced by rTMS. In order to better elucidate this meta-plasticity, rTMS-induced changes in motor cortex excitability have been monitored in various studies in a pre-post stimulation design. Here, we give a literature review of studies investigating motor cortex excitability changes as a neuronal marker for rTMS effects over non-motor cortical areas. A systematic literature review in April 2014 resulted in 29 articles in which motor cortex excitability was assessed before and after rTMS over non-motor areas. The majority of the studies focused on the stimulation of one of three separate cortical areas: the prefrontal area (17 studies), the cerebellum (8 studies), or the temporal cortex (3 studies). One study assessed the effects of multi-site rTMS. Most studies investigated healthy controls but some also stimulated patients with neuropsychiatric conditions (e.g., affective disorders, tinnitus). Methods and findings of the identified studies were highly variable showing no clear systematic pattern of interaction of non-motor rTMS with measures of motor cortex excitability. Based on the available literature, the measurement of motor cortex excitability changes before and after non-motor rTMS has only limited value in the investigation of rTMS related meta-plasticity as a neuronal state or as a trait marker for neuropsychiatric diseases. Our results do not suggest that there are systematic alterations of cortical excitability changes during rTMS treatment, which calls into question the practice of re-adjusting the stimulation intensity according to the motor threshold over the course of the treatment. PMID- 26257635 TI - Fear avoidance beliefs in back pain-free subjects are reflected by amygdala cingulate responses. AB - In most individuals suffering from chronic low back pain, psychosocial factors, specifically fear avoidance beliefs (FABs), play central roles in the absence of identifiable organic pathology. On a neurobiological level, encouraging research has shown brain system correlates of somatic and psychological factors during the transition from (sub) acute to chronic low back pain. The characterization of brain imaging signatures in pain-free individuals before any injury will be of high importance regarding the identification of relevant networks for low back pain (LBP) vulnerability. Fear-avoidance beliefs serve as strong predictors of disability and chronification in LBP and current research indicates that back pain related FABs already exist in the general and pain-free population. Therefore, we aimed at investigating possible differential neural functioning between high- and low fear-avoidant individuals in the general population using functional magnetic resonance imaging. Results revealed that pain-free individuals without a history of chronic pain episodes could be differentiated in amygdala activity and connectivity to the pregenual anterior cingulate cortex by their level of back pain related FABs. These results shed new light on brain networks underlying psychological factors that may become relevant for enhanced disability in a future LBP episode. PMID- 26257634 TI - Many neighbors are not silent. fMRI evidence for global lexical activity in visual word recognition. AB - Many neurocognitive studies investigated the neural correlates of visual word recognition, some of which manipulated the orthographic neighborhood density of words and nonwords believed to influence the activation of orthographically similar representations in a hypothetical mental lexicon. Previous neuroimaging research failed to find evidence for such global lexical activity associated with neighborhood density. Rather, effects were interpreted to reflect semantic or domain general processing. The present fMRI study revealed effects of lexicality, orthographic neighborhood density and a lexicality by orthographic neighborhood density interaction in a silent reading task. For the first time we found greater activity for words and nonwords with a high number of neighbors. We propose that this activity in the dorsomedial prefrontal cortex reflects activation of orthographically similar codes in verbal working memory thus providing evidence for global lexical activity as the basis of the neighborhood density effect. The interaction of lexicality by neighborhood density in the ventromedial prefrontal cortex showed lower activity in response to words with a high number compared to nonwords with a high number of neighbors. In the light of these results the facilitatory effect for words and inhibitory effect for nonwords with many neighbors observed in previous studies can be understood as being due to the operation of a fast-guess mechanism for words and a temporal deadline mechanism for nonwords as predicted by models of visual word recognition. Furthermore, we propose that the lexicality effect with higher activity for words compared to nonwords in inferior parietal and middle temporal cortex reflects the operation of an identification mechanism based on local lexico-semantic activity. PMID- 26257633 TI - Cognitive neuroscience of human counterfactual reasoning. AB - Counterfactual reasoning is a hallmark of human thought, enabling the capacity to shift from perceiving the immediate environment to an alternative, imagined perspective. Mental representations of counterfactual possibilities (e.g., imagined past events or future outcomes not yet at hand) provide the basis for learning from past experience, enable planning and prediction, support creativity and insight, and give rise to emotions and social attributions (e.g., regret and blame). Yet remarkably little is known about the psychological and neural foundations of counterfactual reasoning. In this review, we survey recent findings from psychology and neuroscience indicating that counterfactual thought depends on an integrative network of systems for affective processing, mental simulation, and cognitive control. We review evidence to elucidate how these mechanisms are systematically altered through psychiatric illness and neurological disease. We propose that counterfactual thinking depends on the coordination of multiple information processing systems that together enable adaptive behavior and goal-directed decision making and make recommendations for the study of counterfactual inference in health, aging, and disease. PMID- 26257637 TI - Role of the site of synaptic competition and the balance of learning forces for Hebbian encoding of probabilistic Markov sequences. AB - The majority of distinct sensory and motor events occur as temporally ordered sequences with rich probabilistic structure. Sequences can be characterized by the probability of transitioning from the current state to upcoming states (forward probability), as well as the probability of having transitioned to the current state from previous states (backward probability). Despite the prevalence of probabilistic sequencing of both sensory and motor events, the Hebbian mechanisms that mold synapses to reflect the statistics of experienced probabilistic sequences are not well understood. Here, we show through analytic calculations and numerical simulations that Hebbian plasticity (correlation, covariance, and STDP) with pre-synaptic competition can develop synaptic weights equal to the conditional forward transition probabilities present in the input sequence. In contrast, post-synaptic competition can develop synaptic weights proportional to the conditional backward probabilities of the same input sequence. We demonstrate that to stably reflect the conditional probability of a neuron's inputs and outputs, local Hebbian plasticity requires balance between competitive learning forces that promote synaptic differentiation and homogenizing learning forces that promote synaptic stabilization. The balance between these forces dictates a prior over the distribution of learned synaptic weights, strongly influencing both the rate at which structure emerges and the entropy of the final distribution of synaptic weights. Together, these results demonstrate a simple correspondence between the biophysical organization of neurons, the site of synaptic competition, and the temporal flow of information encoded in synaptic weights by Hebbian plasticity while highlighting the utility of balancing learning forces to accurately encode probability distributions, and prior expectations over such probability distributions. PMID- 26257636 TI - Event-based prospective memory in patients with Parkinson's disease: the effect of emotional valence. AB - The present study investigated the effect of Parkinson's disease (PD) on prospective memory (PM) tasks by varying the emotional content of the PM actions. Twenty-one older adults with PD and 25 healthy older adults took part in the present study. Participants performed three virtual days in the Virtual Week task. On each virtual day, participants performed actions with positive, negative or neutral content. Immediately following each virtual day, participants completed a recognition task to assess their retrospective memory for the various PM tasks. PD patients were less accurate than the control group at both PM accuracy and recognition task accuracy. The effect of emotional valence was also evident, indicating that all participants were more accurate on positive PM tasks than both negative and neutral. This study confirmed PM impairment in PD patients and extended previous research showing how positive emotional stimuli can influence PM performance. PMID- 26257638 TI - Biohybrid Control of General Linear Systems Using the Adaptive Filter Model of Cerebellum. AB - The adaptive filter model of the cerebellar microcircuit has been successfully applied to biological motor control problems, such as the vestibulo-ocular reflex (VOR), and to sensory processing problems, such as the adaptive cancelation of reafferent noise. It has also been successfully applied to problems in robotics, such as adaptive camera stabilization and sensor noise cancelation. In previous applications to inverse control problems, the algorithm was applied to the velocity control of a plant dominated by viscous and elastic elements. Naive application of the adaptive filter model to the displacement (as opposed to velocity) control of this plant results in unstable learning and control. To be more generally useful in engineering problems, it is essential to remove this restriction to enable the stable control of plants of any order. We address this problem here by developing a biohybrid model reference adaptive control (MRAC) scheme, which stabilizes the control algorithm for strictly proper plants. We evaluate the performance of this novel cerebellar-inspired algorithm with MRAC scheme in the experimental control of a dielectric electroactive polymer, a class of artificial muscle. The results show that the augmented cerebellar algorithm is able to accurately control the displacement response of the artificial muscle. The proposed solution not only greatly extends the practical applicability of the cerebellar-inspired algorithm, but may also shed light on cerebellar involvement in a wider range of biological control tasks. PMID- 26257640 TI - A neural network-based exploratory learning and motor planning system for co robots. AB - Collaborative robots, or co-robots, are semi-autonomous robotic agents designed to work alongside humans in shared workspaces. To be effective, co-robots require the ability to respond and adapt to dynamic scenarios encountered in natural environments. One way to achieve this is through exploratory learning, or "learning by doing," an unsupervised method in which co-robots are able to build an internal model for motor planning and coordination based on real-time sensory inputs. In this paper, we present an adaptive neural network-based system for co robot control that employs exploratory learning to achieve the coordinated motor planning needed to navigate toward, reach for, and grasp distant objects. To validate this system we used the 11-degrees-of-freedom RoPro Calliope mobile robot. Through motor babbling of its wheels and arm, the Calliope learned how to relate visual and proprioceptive information to achieve hand-eye-body coordination. By continually evaluating sensory inputs and externally provided goal directives, the Calliope was then able to autonomously select the appropriate wheel and joint velocities needed to perform its assigned task, such as following a moving target or retrieving an indicated object. PMID- 26257639 TI - Learning touch preferences with a tactile robot using dopamine modulated STDP in a model of insular cortex. AB - Neurorobots enable researchers to study how behaviors are produced by neural mechanisms in an uncertain, noisy, real-world environment. To investigate how the somatosensory system processes noisy, real-world touch inputs, we introduce a neurorobot called CARL-SJR, which has a full-body tactile sensory area. The design of CARL-SJR is such that it encourages people to communicate with it through gentle touch. CARL-SJR provides feedback to users by displaying bright colors on its surface. In the present study, we show that CARL-SJR is capable of learning associations between conditioned stimuli (CS; a color pattern on its surface) and unconditioned stimuli (US; a preferred touch pattern) by applying a spiking neural network (SNN) with neurobiologically inspired plasticity. Specifically, we modeled the primary somatosensory cortex, prefrontal cortex, striatum, and the insular cortex, which is important for hedonic touch, to process noisy data generated directly from CARL-SJR's tactile sensory area. To facilitate learning, we applied dopamine-modulated Spike Timing Dependent Plasticity (STDP) to our simulated prefrontal cortex, striatum, and insular cortex. To cope with noisy, varying inputs, the SNN was tuned to produce traveling waves of activity that carried spatiotemporal information. Despite the noisy tactile sensors, spike trains, and variations in subject hand swipes, the learning was quite robust. Further, insular cortex activities in the incremental pathway of dopaminergic reward system allowed us to control CARL-SJR's preference for touch direction without heavily pre-processed inputs. The emerged behaviors we found in this model match animal's behaviors wherein they prefer touch in particular areas and directions. Thus, the results in this paper could serve as an explanation on the underlying neural mechanisms for developing tactile preferences and hedonic touch. PMID- 26257641 TI - The origin of glutamatergic synaptic inputs controls synaptic plasticity and its modulation by alcohol in mice nucleus accumbens. AB - It is widely accepted that long-lasting changes of synaptic strength in the nucleus accumbens (NAc), a brain region involved in drug reward, mediate acute and chronic effects of alcohol. However, our understanding of the mechanisms underlying the effects of alcohol on synaptic plasticity is limited by the fact that the NAc receives glutamatergic inputs from distinct brain regions (e.g., the prefrontal cortex (PFCx), the amygdala and the hippocampus), each region providing different information (e.g., spatial, emotional and cognitive). Combining whole-cell patch-clamp recordings and the optogenetic technique, we examined synaptic plasticity, and its regulation by alcohol, at cortical, hippocampal and amygdala inputs in fresh slices of mouse tissue. We showed that the origin of synaptic inputs determines the basic properties of glutamatergic synaptic transmission, the expression of spike-timing dependent long-term depression (tLTD) and long-term potentiation (LTP) and long-term potentiation (tLTP) and their regulation by alcohol. While we observed both tLTP and tLTD at amygadala and hippocampal synapses, we showed that cortical inputs only undergo tLTD. Functionally, we provide evidence that acute Ethyl Alcohol (EtOH) has little effects on higher order information coming from the PFCx, while severely impacting the ability of emotional and contextual information to induce long lasting changes of synaptic strength. PMID- 26257643 TI - Multi-domain training in healthy old age: Hotel Plastisse as an iPad-based serious game to systematically compare multi-domain and single-domain training. AB - Finding effective training interventions for declining cognitive abilities in healthy aging is of great relevance, especially in view of the demographic development. Since it is assumed that transfer from the trained to untrained domains is more likely to occur when training conditions and transfer measures share a common underlying process, multi-domain training of several cognitive functions should increase the likelihood of such an overlap. In the first part, we give an overview of the literature showing that cognitive training using complex tasks, such as video games, leisure activities, or practicing a series of cognitive tasks, has shown promising results regarding transfer to a number of cognitive functions. These studies, however, do not allow direct inference about the underlying functions targeted by these training regimes. Custom-designed serious games allow to design training regimes according to specific cognitive functions and a target population's need. In the second part, we introduce the serious game Hotel Plastisse as an iPad-based training tool for older adults that allows the comparison of the simultaneous training of spatial navigation, visuomotor function, and inhibition to the training of each of these functions separately. Hotel Plastisse not only defines the cognitive functions of the multi domain training clearly, but also implements training in an interesting learning environment including adaptive difficulty and feedback. We propose this novel training tool with the goal of furthering our understanding of how training regimes should be designed in order to affect cognitive functioning of older adults most broadly. PMID- 26257644 TI - Specific cognitive functions and depressive symptoms as predictors of activities of daily living in older adults with heterogeneous cognitive backgrounds. AB - Cognitive functioning influences activities of daily living (ADL). However, studies reporting the association between ADL and neuropsychological performance show inconsistent results regarding what specific cognitive domains are related to each specific functional domains. Additionally, whether depressive symptoms are associated with a worse functional performance in older adults is still under explored. We investigated if specific cognitive domains and depressive symptoms would affect different aspects of ADL. Participants were 274 older adults (96 normal aging participants, 85 patients with mild cognitive impairment, and 93 patients probable with mild Alzheimer's disease dementia) with low formal education (~4 years). Measures of ADL included three complexity levels: Self care, Instrumental-Domestic, and Instrumental-Complex. The specific cognitive functions were evaluated through a factorial strategy resulting in four cognitive domains: Executive Functions, Language/Semantic Memory, Episodic Memory, and Visuospatial Abilities. The Geriatric Depression Scale measured depressive symptoms. Multiple linear regression analysis showed executive functions and episodic memory as significant predictors of Instrumental-Domestic ADL, and executive functions, episodic memory and language/semantic memory as predictors of Instrumental-Complex ADL (22 and 28% of explained variance, respectively). Ordinal regression analysis showed the influence of specific cognitive functions and depressive symptoms on each one of the instrumental ADL. We observed a heterogeneous pattern of association with explained variance ranging from 22 to 38%. Different instrumental ADL had specific cognitive predictors and depressive symptoms were predictive of ADL involving social contact. Our results suggest a specific pattern of influence depending on the specific instrumental daily living activity. PMID- 26257642 TI - Microglial cell dysregulation in brain aging and neurodegeneration. AB - Aging is the main risk factor for neurodegenerative diseases. In aging, microglia undergoes phenotypic changes compatible with their activation. Glial activation can lead to neuroinflammation, which is increasingly accepted as part of the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). We hypothesize that in aging, aberrant microglia activation leads to a deleterious environment and neurodegeneration. In aged mice, microglia exhibit an increased expression of cytokines and an exacerbated inflammatory response to pathological changes. Whereas LPS increases nitric oxide (NO) secretion in microglia from young mice, induction of reactive oxygen species (ROS) predominates in older mice. Furthermore, there is accumulation of DNA oxidative damage in mitochondria of microglia during aging, and also an increased intracellular ROS production. Increased ROS activates the redox-sensitive nuclear factor kappa B, which promotes more neuroinflammation, and can be translated in functional deficits, such as cognitive impairment. Mitochondria-derived ROS and cathepsin B, are also necessary for the microglial cell production of interleukin 1beta, a key inflammatory cytokine. Interestingly, whereas the regulatory cytokine TGFbeta1 is also increased in the aged brain, neuroinflammation persists. Assessing this apparent contradiction, we have reported that TGFbeta1 induction and activation of Smad3 signaling after inflammatory stimulation are reduced in adult mice. Other protective functions, such as phagocytosis, although observed in aged animals, become not inducible by inflammatory stimuli and TGFbeta1. Here, we discuss data suggesting that mitochondrial and endolysosomal dysfunction could at least partially mediate age-associated microglial cell changes, and, together with the impairment of the TGFbeta1-Smad3 pathway, could result in the reduction of protective activation and the facilitation of cytotoxic activation of microglia, resulting in the promotion of neurodegenerative diseases. PMID- 26257646 TI - "Are we ready for robots that care for us?" Attitudes and opinions of older adults toward socially assistive robots. AB - Socially Assistive Robots (SAR) may help improve care delivery at home for older adults with cognitive impairment and reduce the burden of informal caregivers. Examining the views of these stakeholders on SAR is fundamental in order to conceive acceptable and useful SAR for dementia care. This study investigated SAR acceptance among three groups of older adults living in the community: persons with Mild Cognitive Impairment, informal caregivers of persons with dementia, and healthy older adults. Different technology acceptance questions related to the robot and user characteristics, potential applications, feelings about technology, ethical issues, and barriers and facilitators for SAR adoption, were addressed in a mixed-method study. Participants (n = 25) completed a survey and took part in a focus group (n = 7). A functional robot prototype, a multimedia presentation, and some use-case scenarios provided a base for the discussion. Content analysis was carried out based on recorded material from focus groups. Results indicated that an accurate insight of influential factors for SAR acceptance could be gained by combining quantitative and qualitative methods. Participants acknowledged the potential benefits of SAR for supporting care at home for individuals with cognitive impairment. In all the three groups, intention to use SAR was found to be lower for the present time than that anticipated for the future. However, caregivers and persons with MCI had a higher perceived usefulness and intention to use SAR, at the present time, than healthy older adults, confirming that current needs are strongly related to technology acceptance and should influence SAR design. A key theme that emerged in this study was the importance of customizing SAR appearance, services, and social capabilities. Mismatch between needs and solutions offered by the robot, usability factors, and lack of experience with technology, were seen as the most important barriers for SAR adoption. PMID- 26257647 TI - Role of diffuse low-level heteroplasmy of mitochondrial DNA in Alzheimer's disease neurodegeneration. AB - Alzheimer's disease (AD) is the most common form of dementia in the elderly. The vast majority of cases are not linked to a known genetic defect and the molecular mechanisms underlying AD pathogenesis are still elusive. Evidence suggests that mitochondrial dysfunction is a prominent feature of the disease, and that mitochondrial DNA (mtDNA) alterations may represent a possible starting point of the pathophysiological cascade. Although specific mtDNA alterations have been reported in AD patients both in brain and peripheral tissues, such as D-loop mutations, 4977-bp deletion and poly-C tract D310 cytosine insertion, a generalized subtle allelic shift has also been demonstrated. This shift is significant for a few nucleotide positions (nps), but it is also detectable for most nps, although at a lower level. As single allelic substitutions can unlikely be determinant, it is proposed that the combination of all of them could lead to a less efficient oxidative phosphorylation, thus influencing AD development and course. PMID- 26257645 TI - The quasi-parallel lives of satellite cells and atrophying muscle. AB - Skeletal muscle atrophy or wasting accompanies various chronic illnesses and the aging process, thereby reducing muscle function. One of the most important components contributing to effective muscle repair in postnatal organisms, the satellite cells (SCs), have recently become the focus of several studies examining factors participating in the atrophic process. We critically examine here the experimental evidence linking SC function with muscle loss in connection with various diseases as well as aging, and in the subsequent recovery process. Several recent reports have investigated the changes in SCs in terms of their differentiation and proliferative capacity in response to various atrophic stimuli. In this regard, we review the molecular changes within SCs that contribute to their dysfunctional status in atrophy, with the intention of shedding light on novel potential pharmacological targets to counteract the loss of muscle mass. PMID- 26257648 TI - The effects of lifelong blindness on murine neuroanatomy and gene expression. AB - Mammalian neocortical development is regulated by neural patterning mechanisms, with distinct sensory and motor areas arising through the process of arealization. This development occurs alongside developing central or peripheral sensory systems. Specifically, the parcellation of neocortex into specific areas of distinct cytoarchitecture, connectivity and function during development is reliant upon both cortically intrinsic mechanisms, such as gene expression, and extrinsic processes, such as input from the sensory receptors. This developmental program shifts from patterning to maintenance as the animal ages and is believed to be active throughout life, where the brain's organization is stable yet plastic. In this study, we characterize the long-term effects of early removal of visual input via bilateral enucleation at birth. To understand the long-term effects of early blindness we conducted anatomical and molecular assays 18 months after enucleation, near the end of lifespan in the mouse. Bilateral enucleation early in life leads to long-term, stable size reductions of the thalamic lateral geniculate nucleus (LGN) and the primary visual cortex (V1) alongside a increase in individual whisker barrel size. Neocortical gene expression in the aging brain has not been previously identified; we document cortical expression of multiple regionalization genes. Expression patterns of Ephrin A5, COUP-TFI, and RZRbeta and patterns of intraneocortical connectivity (INC) are altered in the neocortices of aging blind mice. Sensory inputs from different modalities during development likely play a major role in the development of cortical areal and thalamic nuclear boundaries. We suggest that early patterning by prenatal retinal activity combined with persistent gene expression within the thalamus and cortex is sufficient to establish and preserve a small but present LGN and V1 into late adulthood. PMID- 26257649 TI - Dendrogenin A and B two new steroidal alkaloids increasing neural responsiveness in the deafened guinea pig. AB - AIM: To investigate the therapeutic potential for treating inner ear damage of two new steroidal alkaloid compounds, Dendrogenin A and Dendrogenin B, previously shown to be potent inductors of cell differentiation. METHODS: Guinea pigs, unilaterally deafened by neomycin infusion, received a cochlear implant followed by immediate or a 2-week delayed treatment with Dendrogenin A, Dendrogenin B, and, as comparison artificial perilymph and glial cell-line derived neurotrophic factor. After a 4-week treatment period the animals were sacrificed and the cochleae processed for morphological analysis. Electrically-evoked auditory brainstem responses (eABRs) were measured weekly throughout the experiment. RESULTS: Following immediate or delayed Dendrogenin treatment the electrical responsiveness was significantly maintained, in a similar extent as has been shown using neurotrophic factors. Histological analysis showed that the spiral ganglion neurons density was only slightly higher than the untreated group. CONCLUSIONS: Our results suggest that Dendrogenins constitute a new class of drugs with strong potential to improve cochlear implant efficacy and to treat neuropathy/synaptopathy related hearing loss. That electrical responsiveness was maintained despite a significantly reduced neural population suggests that the efficacy of cochlear implants is more related to the functional state of the spiral ganglion neurons than merely their number. PMID- 26257651 TI - Simultaneous inhibition of ATR and PARP sensitizes colon cancer cell lines to irinotecan. AB - Enhanced DNA damage repair is one mechanism involved in colon cancer drug resistance. Thus, targeting molecular components of repair pathways with specific small molecule inhibitors may improve the efficacy of chemotherapy. ABT-888 and VE-821, inhibitors of poly-ADP-ribose-polymerase (PARP) and the serine/threonine kinase Ataxia telangiectasia related (ATR), respectively, were used to treat colon cancer cell lines in combination with the topoisomerase-I inhibitor irinotecan (SN38). Our findings show that each of these DNA repair inhibitors utilized alone at nontoxic single agent concentrations resulted in sensitization to SN38 producing a 1.4-3 fold reduction in the 50% inhibitory concentration (IC50) of SN38 in three colon cancer cell lines. When combined together, nontoxic concentrations of ABT-888 and VE-821 produced a 4.5-27 fold reduction in the IC50 of SN38 with the HCT-116 colon cancer cells demonstrating the highest sensitization as compared to LoVo and HT-29 colon cancer cells. Furthermore, the combination of all three agents was associated with maximal G2 -M arrest and enhanced DNA-damage (gammaH2AX) in all three colon cancer cell lines. The mechanism of this enhanced sensitization was associated with: (a) maximal suppression of SN38 induced PARP activity in the presence of both inhibitors and (b) ABT-888 producing partial abrogation of the VE-821 enhancement of SN38 induced DNA-PK phosphorylation, resulting in more unrepaired DNA damage; these alterations were only present in the HCT-116 cells which have reduced levels of ATM. This novel combination of DNA repair inhibitors may be useful to enhance the activity of DNA damaging chemotherapies such as irinotecan and help produce sensitization to this drug in colon cancer. PMID- 26257652 TI - Extracellular signal-regulated kinases 1/2 as regulators of cardiac hypertrophy. AB - Cardiac hypertrophy results from increased mechanical load on the heart and through the actions of local and systemic neuro-humoral factors, cytokines and growth factors. These mechanical and neuroendocrine effectors act through stretch, G protein-coupled receptors and tyrosine kinases to induce the activation of a myriad of intracellular signaling pathways including the extracellular signal-regulated kinases 1/2 (ERK1/2). Since most stimuli that provoke myocardial hypertrophy also elicit an acute phosphorylation of the threonine-glutamate-tyrosine (TEY) motif within the activation loops of ERK1 and ERK2 kinases, resulting in their activation, ERKs have long been considered promotors of cardiac hypertrophy. Several mouse models were generated in order to directly understand the causal role of ERK1/2 activation in the heart. These models include direct manipulation of ERK1/2 such as overexpression, mutagenesis or knockout models, manipulations of upstream kinases such as MEK1 and manipulations of the phosphatases that dephosphorylate ERK1/2 such as DUSP6. The emerging understanding from these studies, as will be discussed here, is more complex than originally considered. While there is little doubt that ERK1/2 activation or the lack of it modulates the hypertrophic process or the type of hypertrophy that develops, it appears that not all ERK1/2 activation events are the same. While much has been learned, some questions remain regarding the exact role of ERK1/2 in the heart, the upstream events that result in ERK1/2 activation and the downstream effector in hypertrophy. PMID- 26257650 TI - Serotonin, neural markers, and memory. AB - Diverse neuropsychiatric disorders present dysfunctional memory and no effective treatment exits for them; likely as result of the absence of neural markers associated to memory. Neurotransmitter systems and signaling pathways have been implicated in memory and dysfunctional memory; however, their role is poorly understood. Hence, neural markers and cerebral functions and dysfunctions are revised. To our knowledge no previous systematic works have been published addressing these issues. The interactions among behavioral tasks, control groups and molecular changes and/or pharmacological effects are mentioned. Neurotransmitter receptors and signaling pathways, during normal and abnormally functioning memory with an emphasis on the behavioral aspects of memory are revised. With focus on serotonin, since as it is a well characterized neurotransmitter, with multiple pharmacological tools, and well characterized downstream signaling in mammals' species. 5-HT1A, 5-HT4, 5-HT5, 5-HT6, and 5-HT7 receptors as well as SERT (serotonin transporter) seem to be useful neural markers and/or therapeutic targets. Certainly, if the mentioned evidence is replicated, then the translatability from preclinical and clinical studies to neural changes might be confirmed. Hypothesis and theories might provide appropriate limits and perspectives of evidence. PMID- 26257653 TI - Inhibition of voltage-gated sodium channels by sumatriptan bioisosteres. AB - Voltage-gated sodium channels are known to play a pivotal role in perception and transmission of pain sensations. Gain-of-function mutations in the genes encoding the peripheral neuronal sodium channels, hNav1.7-1.9, cause human painful diseases. Thus while treatment of chronic pain remains an unmet clinical need, sodium channel blockers are considered as promising druggable targets. In a previous study, we evaluated the analgesic activity of sumatriptan, an agonist of serotonin 5HT1B/D receptors, and some new chiral bioisosteres, using the hot plate test in the mouse. Interestingly, we observed that the analgesic effectiveness was not necessarily correlated to serotonin agonism. In this study, we evaluated whether sumatriptan and its congeners may inhibit heterologously expressed hNav1.7 sodium channels using the patch-clamp method. We show that sumatriptan blocks hNav1.7 channels only at very high, supratherapeutic concentrations. In contrast, its three analogs, namely 20b, (R)-31b, and (S)-22b, exert a dose and use-dependent sodium channel block. At 0.1 and 10 Hz stimulation frequencies, the most potent compound, (S)-22b, was 4.4 and 1.7 fold more potent than the well-known sodium channel blocker mexiletine. The compound induces a negative shift of voltage dependence of fast inactivation, suggesting higher affinity to the inactivated channel. Accordingly, we show that (S)-22b likely binds the conserved local anesthetic receptor within voltage-gated sodium channels. Combining these results with the previous ones, we hypothesize that use dependent sodium channel blockade contributes to the analgesic activity of (R) 31b and (S)-22b. These later compounds represent promising lead compounds for the development of efficient analgesics, the mechanism of action of which may include a dual action on sodium channels and 5HT1D receptors. PMID- 26257655 TI - Docosahexaenoic (DHA) modulates phospholipid-hydroperoxide glutathione peroxidase (Gpx4) gene expression to ensure self-protection from oxidative damage in hippocampal cells. AB - Docosahexaenoic acid (DHA, 22:6n-3) is a unique polyunsaturated fatty acid particularly abundant in nerve cell membrane phospholipids. DHA is a pleiotropic molecule that, not only modulates the physicochemical properties and architecture of neuronal plasma membrane, but it is also involved in multiple facets of neuronal biology, from regulation of synaptic function to neuroprotection and modulation of gene expression. As a highly unsaturated fatty acid due to the presence of six double bonds, DHA is susceptible for oxidation, especially in the highly pro-oxidant environment of brain parenchyma. We have recently reported the ability of DHA to regulate the transcriptional program controlling neuronal antioxidant defenses in a hippocampal cell line, especially the glutathione/glutaredoxin system. Within this antioxidant system, DHA was particularly efficient in triggering the upregulation of Gpx4 gene, which encodes for the nuclear, cytosolic, and mitochondrial isoforms of phospholipid hydroperoxide glutathione peroxidase (PH-GPx/GPx4), the main enzyme protecting cell membranes against lipid peroxidation and capable to reduce oxidized phospholipids in situ. We show here that this novel property of DHA is also significant in the hippocampus of wild-type mice and, to a lesser extent in APP/PS1 transgenic mice, a familial model of Alzheimer's disease. By doing this, DHA stimulates a mechanism to self-protect from oxidative damage even in the neuronal scenario of high aerobic metabolism and in the presence of elevated levels of transition metals, which inevitably favor the generation of reactive oxygen species. Noticeably, DHA also upregulated a Gpx4 CIRT (Cytoplasmic Intron sequence Retaining Transcripts), a novel Gpx4 splicing variant, harboring part of the first intronic region, which according to the "sentinel RNA hypothesis" would expand the ability of Gpx4 (and DHA) to provide neuronal antioxidant defense independently of conventional nuclear splicing in cellular compartments, like dendritic zones, located away from nuclear compartment. We discuss here, the crucial role of this novel transcriptional regulation triggered by DHA in the context of normal and pathological hippocampal cell. PMID- 26257654 TI - Ongoing controversies surrounding cardiac remodeling: is it black and white-or rather fifty shades of gray? AB - Cardiac remodeling describes the heart's multimodal response to a myriad of external or intrinsic stimuli and stressors most of which are probably only incompletely elucidated to date. Over many years the signaling molecules involved in these remodeling processes have been dichotomized according to a classic antagonistic view of black and white, i.e., attributed either a solely maladaptive or entirely beneficial character. By dissecting controversies, recent developments and shifts in perspective surrounding the three major cardiac signaling molecules calcineurin (Cn), protein kinase A (PKA) and calcium/calmodulin-dependent kinase II (CaMKII), this review challenges this dualistic view and advocates the nature and dignity of each of these key mediators of cardiac remodeling as a multilayered, highly context-sensitive and sophisticated continuum that can be markedly swayed and influenced by a multitude of environmental factors and crosstalk mechanisms. Furthermore this review delineates the importance and essential contributions of degradation and proteolysis to cardiac plasticity and homeostasis and finally aims to integrate the various aspects of protein synthesis and turnover into a comprehensive picture. PMID- 26257656 TI - Recovery from exercise: vulnerable state, window of opportunity, or crystal ball? AB - Why should we study the recovery from exercise as a discrete phenomenon from exercise itself? We identify three distinct (but not mutually exclusive) rationales that drive the need to investigate the physiology of recovery from exercise. (1) Some individuals are at a heightened risk of clinical outcomes in the immediate post-exercise period; thus the potential negative outcomes of this "vulnerable state" must be weighed against the numerous benefits of exercise training, and may be mitigated to reduce risk. (2) Many of the signaling mechanisms responsible for the beneficial effects of exercise training remain amplified during the exercise recovery period, and may present a "window of opportunity" that can be exploited by interventions to enhance the beneficial adaptations to exercise training, especially in clinical populations. (3) On an individual level, exercise recovery responses may provide investigators with a "crystal ball" ability to predict future clinical outcomes even in apparently healthy individuals. In short, the physiology of recovery is a multi-faceted and complex process, likely involving systems and pathways that are distinct from the physiology of exercise itself. For these reasons, it merits ongoing study. PMID- 26257657 TI - Enteric motor pattern generators involve both myogenic and neurogenic mechanisms in the human colon. PMID- 26257658 TI - Evidence for water deficit-induced mass increases of raffinose family oligosaccharides (RFOs) in the leaves of three Craterostigma resurrection plant species. AB - The leaves of the resurrection plant Craterostigma plantagineum accumulate sucrose during dehydration, via a conversion from the unusual C8 ketose-sugar 2 octulose. However, raffinose family oligosaccharides (RFOs) have been shown to be major photosynthetic products in this plant. The tetrasaccharide stachyose is the major phloem-mobile carbohydrate and is used as a carbon store in roots. It has been suggested that this carbon store is remobilized during rehydration, presumably for cellular repair processes. We examined the effects of water deficit on the leaf water-soluble carbohydrate profiles of three Craterostigma species. Apart from the classical 2-octulose-to-sucrose interconversion, there was a strong water deficit-associated mass increase of RFOs up to the pentasaccharide verbascose. However, the activities of three dedicated RFO biosynthetic enzymes (raffinose, stachyose, and verbascose synthase) was not correlated with RFO accumulation, suggesting that biosynthetic enzyme activities measured in the early stages of water-deficit were sufficient to synthesize enough galactinol and lead to RFO accumulation in the leaves. Our findings are suggestive of RFOs providing additional carbohydrate-based stress protection to the leaves of these plants during the desiccated state. PMID- 26257659 TI - Transcriptome analysis and RNA interference of cockroach phototransduction indicate three opsins and suggest a major role for TRPL channels. AB - Our current understanding of insect phototransduction is based on a small number of species, but insects occupy many different visual environments. We created the retinal transcriptome of a nocturnal insect, the cockroach, Periplaneta americana to identify proteins involved in the earliest stages of compound eye phototransduction, and test the hypothesis that different visual environments are reflected in different molecular contributions to function. We assembled five novel mRNAs: two green opsins, one UV opsin, and one each TRP and TRPL ion channel homologs. One green opsin mRNA (pGO1) was 100-1000 times more abundant than the other opsins (pGO2 and pUVO), while pTRPL mRNA was 10 times more abundant than pTRP, estimated by transcriptome analysis or quantitative PCR (qPCR). Electroretinograms were used to record photoreceptor responses. Gene specific in vivo RNA interference (RNAi) was achieved by injecting long (596-708 bp) double-stranded RNA into head hemolymph, and verified by qPCR. RNAi of the most abundant green opsin reduced both green opsins by more than 97% without affecting UV opsin, and gave a maximal reduction of 75% in ERG amplitude 7 days after injection that persisted for at least 19 days. RNAi of pTRP and pTRPL genes each specifically reduced the corresponding mRNA by 90%. Electroretinogram (ERG) reduction by pTRPL RNAi was slower than for opsin, reaching 75% attenuation by 21 days, without recovery at 29 days. pTRP RNAi attenuated ERG much less; only 30% after 21 days. Combined pTRP plus pTRPL RNAi gave only weak evidence of any cooperative interactions. We conclude that silencing retinal genes by in vivo RNAi using long dsRNA is effective, that visible light transduction in Periplaneta is dominated by pGO1, and that pTRPL plays a major role in cockroach phototransduction. PMID- 26257660 TI - Mental Imagery and Post-Traumatic Stress Disorder: A Neuroimaging and Experimental Psychopathology Approach to Intrusive Memories of Trauma. AB - This hypothesis and theory paper presents a pragmatic framework to help bridge the clinical presentation and neuroscience of intrusive memories following psychological trauma. Intrusive memories are a hallmark symptom of post-traumatic stress disorder (PTSD). However, key questions, including those involving etiology, remain. In particular, we know little about the brain mechanisms involved in why only some moments of the trauma return as intrusive memories while others do not. We first present an overview of the patient experience of intrusive memories and the neuroimaging studies that have investigated intrusive memories in PTSD patients. Next, one mechanism of how to model intrusive memories in the laboratory, the trauma film paradigm, is examined. In particular, we focus on studies combining the trauma film paradigm with neuroimaging. Stemming from the clinical presentation and our current understanding of the processes involved in intrusive memories, we propose a framework in which an intrusive memory comprises five component parts; autobiographical (trauma) memory, involuntary recall, negative emotions, attention hijacking, and mental imagery. Each component part is considered in turn, both behaviorally and from a brain imaging perspective. A mapping of these five components onto our understanding of the brain is described. Unanswered questions that exist in our understanding of intrusive memories are considered using the proposed framework. Overall, we suggest that mental imagery is key to bridging the experience, memory, and intrusive recollection of the traumatic event. Further, we suggest that by considering the brain mechanisms involved in the component parts of an intrusive memory, in particular mental imagery, we may be able to aid the development of a firmer bridge between patients' experiences of intrusive memories and the clinical neuroscience behind them. PMID- 26257662 TI - Social-cognitive barriers to ethical authorship. PMID- 26257661 TI - Investigating the Role of Hippocampal BDNF in Anxiety Vulnerability Using Classical Eyeblink Conditioning. AB - Dysregulation of brain-derived neurotrophic factor (BDNF), behavioral inhibition temperament (BI), and small hippocampal volume have been linked to anxiety disorders. Individuals with BI show facilitated acquisition of the classically conditioned eyeblink response (CCER) as compared to non-BI individuals, and a similar pattern is seen in an animal model of BI, the Wistar-Kyoto (WKY) rat. The present study examined the role of hippocampal BDNF in the facilitated delay CCER of WKY rats. Consistent with earlier work, acquisition was facilitated in WKY rats compared to the Sprague Dawley (SD) rats. Facilitated acquisition was associated with increased BDNF, TrkB, and Arc mRNA in the dentate gyrus of SD rats, but learning-induced increases in BDNF and Arc mRNA were significantly smaller in WKY rats. To determine whether reduced hippocampal BDNF in WKY rats was a contributing factor for their facilitated CCER, BDNF or saline infusions were given bilaterally into the dentate gyrus region 1 h prior to training. BDNF infusion did not alter the acquisition of SD rats, but significantly dampened the acquisition of CCER in the WKY rats, such that acquisition was similar to SD rats. Together, these results suggest that inherent differences in the BDNF system play a critical role in the facilitated associative learning exhibited by WKY rats, and potentially individuals with BI. Facilitated associative learning may represent a vulnerability factor in the development of anxiety disorders. PMID- 26257663 TI - Infants' neural responses to facial emotion in the prefrontal cortex are correlated with temperament: a functional near-infrared spectroscopy study. AB - Accurate decoding of facial expressions is critical for human communication, particularly during infancy, before formal language has developed. Different facial emotions elicit distinct neural responses within the first months of life. However, there are broad individual differences in such responses, so that the same emotional expression can elicit different brain responses in different infants. In this study, we sought to investigate such differences in the processing of emotional faces by analyzing infants's cortical metabolic responses to face stimuli and examining whether individual differences in these responses might vary as a function of infant temperament. Seven-month-old infants (N = 24) were shown photographs of women portraying happy expressions, and neural activity was recorded using functional near-infrared spectroscopy (fNIRS). Temperament data were collected using the Revised Infant Behavior Questionnaire Short Form, which assesses the broad temperament factors of Surgency/Extraversion (S/E), Negative Emotionality (NE), and Orienting/Regulation (O/R). We observed that oxyhemoglobin (oxyHb) responses to happy face stimuli were negatively correlated with infant temperament factors in channels over the left prefrontal cortex (uncorrected for multiple comparisons). To investigate the brain activity underlying this association, and to explore the use of fNIRS in measuring cortical asymmetry, we analyzed hemispheric asymmetry with respect to temperament groups. Results showed preferential activation of the left hemisphere in low-NE infants in response to smiling faces. These results suggest that individual differences in temperament are associated with differential prefrontal oxyHb responses to faces. Overall, these analyses contribute to our current understanding of face processing during infancy, demonstrate the use of fNIRS in measuring prefrontal asymmetry, and illuminate the neural correlates of face processing as modulated by temperament. PMID- 26257664 TI - The association between perceived maternal and paternal psychopathology and depression and anxiety symptoms in adolescent girls. AB - Exposure to parental depression and anxiety is known to heighten the risk of internalizing symptoms and disorders in children and adolescents. Ample research has focused on the influence of maternal depression and anxiety, but the contribution of psychopathology in fathers remains unclear. We studied the relationships of perceived maternal and paternal psychopathology with adolescents' depression and anxiety symptoms in a general population sample of 862 adolescent girls (age M = 12.39, SD = 0.79). Assessments included adolescents' self-reports of their own depression and anxiety as well as their reports of maternal and paternal psychopathology. We found that perceived maternal and paternal psychopathology were both related to depression and anxiety symptoms in adolescent girls. A combination of higher maternal and paternal psychopathology was related to even higher levels of depression and anxiety in adolescent girls. Our findings showed that adolescents' perceptions of their parents' psychopathology are significantly related to their own emotional problems. PMID- 26257665 TI - Trust and mindreading in adolescents: the moderating role of social value orientation. AB - In adolescence, aspects of cognition that are required to deal with complex cooperation situations, such as mentalising and social value orientation, are still in development. In the Trust Game, cooperation may lead to better outcomes for both players, but can also lead to exploitation by the trustee. In the present study, we explore how mindreading, a crucial aspect of mentalising, and social value orientation (whether someone is prosocial or proself) are related to trust. In a group of 217 students (51% girls, Mage = 15.1) social value orientation, mindreading and trust (using the Trust Game) were measured. The result show that social value orientation moderates the relation between mindreading and trust. In the group of prosocials, we find no correlation between mindreading and trust. In the group of proselfs, mindreading is negatively correlated to trust, indicating that proselfs use their mentalising skills to assess that the trustee is likely to exploit them. PMID- 26257666 TI - Keeping track of who said what: Performance on a modified auditory n-back task with young and older adults. AB - A modified auditory n-back task was used to examine the ability of young and older listeners to remember the content of spoken messages presented from different locations. The messages were sentences from the Coordinative Response Measure (CRM) corpus, and the task was to judge whether a target word on the current trial was the same as in the most recent presentation from the same location (left, center, or right). The number of trials between comparison items (the number back) was varied while keeping the number of items to be held in memory (the number of locations) constant. Three levels of stimulus uncertainty were evaluated. Low- and high-uncertainty conditions were created by holding the talker (voice) and nontarget words constant, or varying them unpredictably across trials. In a medium-uncertainty condition, each location was associated with a specific talker, thus increasing predictability and ecological validity. Older listeners performed slightly worse than younger listeners, but there was no significant difference in response times (RT) for the two groups. An effect of the number back (n) was seen for both PC and RT; PC decreased steadily with n, while RT was fairly constant after a significant increase from n = 1 to n = 2. Apart from the lower PC for the older group, there was no effect involving age for either PC or RT. There was an effect of target word location (faster RTs with a late-occurring target) and an effect of uncertainty (faster RTs with a constant talker-location mapping, relative to the high-uncertainty condition). A similar pattern of performance was observed with a group of elderly hearing-impaired listeners (with and without shaping to ensure audibility), but RTs were substantially slower and the effect of uncertainty was absent. Apart from the observed overall slowing of RTs, these results provide little evidence for an effect of age-related changes in cognitive abilities on this task. PMID- 26257667 TI - Miscommunication of science: music cognition research in the popular press. PMID- 26257669 TI - Connectedness to Nature and to Humanity: their association and personality correlates. AB - People differ in the extent to which they identify with humans beyond their ingroup and with non-human living things. We refer to the former as the Connectedness to Humanity (CH) and to the latter as the Connectedness to Nature (CN). In a sample of 324 undergraduate students, CH and CN were operationalized using the Identification with All Humanity Scale (McFarland et al., 2012) and the CN Scale (Mayer and Frantz, 2004), respectively. These variables correlated moderately with each other (r = 0.44) and shared Openness to Experience and Honesty-Humility as their primary personality correlates. CN was found to play an important role in mediating the relationships between the two personality variables and some specific pro-environmental/pro-animal attitudes and ecological behaviors. PMID- 26257670 TI - Self-reported sleep duration mitigates the association between inflammation and cognitive functioning in hospitalized older men. AB - Examination of predictors of late-life cognitive functioning is particularly salient in at-risk older adults, such as those who have been recently hospitalized. Sleep and inflammation are independently related to late-life cognitive functioning. The potential role of sleep as a moderator of the relationship between inflammation and global cognitive functioning has not been adequately addressed. We examined the relationship between self-reported sleep duration, inflammatory markers, and general cognitive functioning in hospitalized older men. Older men (n = 135; Mean age = 72.9 +/- 9.7 years) were recruited from inpatient rehabilitation units at a VA Medical Center to participate in a cross sectional study of sleep. Participants completed the Mini-Mental State Examination and Pittsburgh Sleep Quality Index, and underwent an 8 a.m. blood draw to measure inflammatory markers [i.e., C-reactive protein (CRP), tumor necrosis factor alpha (TNFalpha), soluble intercellular adhesion molecule-1 (sICAM-1), and interleukin-6 (IL-6)]. Hierarchical regression analyses (controlling for age, education, race, depression, pain, health comorbidity, and BMI) revealed that higher levels of CRP and sICAM are associated with higher global cognitive functioning in older men with sleep duration >=6 h (beta = 0.19, beta = -0.18, p's < 0.05, respectively), but not in those with short sleep durations (p's > 0.05). In elderly hospitalized men, sleep duration moderates the association between inflammation and cognitive functioning. These findings have implications for the clinical care of older men within medical settings. PMID- 26257671 TI - Tears and transformation: feeling like crying as an indicator of insightful or "aesthetic" experience with art. AB - This paper explores a fundamental similarity between cognitive models for crying and conceptions of insight, enlightenment or, in the context of art, "aesthetic experience." All of which center on a process of initial discrepancy, followed by schema change, and conclude in a proposed adjustment or "transformation" of one's self image/world-view. Because tears are argued to mark one of the only physical indicators of this cognitive outcome, and because the process is particularly salient in examples with art, I argue that crying may provide an intriguing marker for empirical study of art experience. To explore this parallel, I offer a review of crying theory as well as of tearful cases with art, pointing out the key cognitive elements. I then introduce an expanded crying model, based upon our recent model of art experience which does consider insight and adjustment or application of the self. I also consider multiple emotional and evaluative factors, which may co-vary with crying response. This theoretical discussion is then applied in three exploratory, survey-based studies conducted within U.K., Japan and U.S. museums, and including what is claimed to be the 20th century's most tear-inducing abstract paintings. Results showed-with cross-cultural consistency-significant relation between "feeling like crying" and a collection of responses posited to indicate a full progression to aesthetic experience, as well as to positive assessment of artwork goodness, beauty, understanding of meaning, and to final reported self reflection and epiphany. I argue that, beyond the question of why we may cry, by considering the implications of what tears may indicate within information processing, feeling like crying may indeed offer a compelling basis for empirically identifying outcomes of perceptual (art) experience. PMID- 26257668 TI - Interoception and stress. AB - Afferent neural signals are continuously transmitted from visceral organs to the brain. Interoception refers to the processing of visceral-afferent neural signals by the central nervous system, which can finally result in the conscious perception of bodily processes. Interoception can, therefore, be described as a prominent example of information processing on the ascending branch of the brain body axis. Stress responses involve a complex neuro-behavioral cascade, which is elicited when the organism is confronted with a potentially harmful stimulus. As this stress cascade comprises a range of neural and endocrine pathways, stress can be conceptualized as a communication process on the descending branch of the brain-body axis. Interoception and stress are, therefore, associated via the bi directional transmission of information on the brain-body axis. It could be argued that excessive and/or enduring activation (e.g., by acute or chronic stress) of neural circuits, which are responsible for successful communication on the brain-body axis, induces malfunction and dysregulation of these information processes. As a consequence, interoceptive signal processing may be altered, resulting in physical symptoms contributing to the development and/or maintenance of body-related mental disorders, which are associated with stress. In the current paper, we summarize findings on psychobiological processes underlying acute and chronic stress and their interaction with interoception. While focusing on the role of the physiological stress axes (hypothalamic-pituitary adrenocortical axis and autonomic nervous system), psychological factors in acute and chronic stress are also discussed. We propose a positive feedback model involving stress (in particular early life or chronic stress, as well as major adverse events), the dysregulation of physiological stress axes, altered perception of bodily sensations, and the generation of physical symptoms, which may in turn facilitate stress. PMID- 26257672 TI - From means and variances to persons and patterns. AB - A novel approach for conceptualizing and analyzing data from psychological studies is presented and discussed. This approach is centered on model building in an effort to explicate the structures and processes believed to generate a set of observations. These models therefore go beyond the variable-based, path models in use today which are limiting with regard to the types of inferences psychologists can draw from their research. In terms of analysis, the newer approach replaces traditional aggregate statistics such as means, variances, and covariances with methods of pattern detection and analysis. While these methods are person-centered and do not require parametric assumptions, they are both demanding and rigorous. They also provide psychologists with the information needed to draw the primary inference they often wish to make from their research; namely, the inference to best explanation. PMID- 26257673 TI - Development of grouped icEEG for the study of cognitive processing. AB - Invasive intracranial EEG (icEEG) offers a unique opportunity to study human cognitive networks at an unmatched spatiotemporal resolution. To date, the contributions of icEEG have been limited to the individual-level analyses or cohorts whose data are not integrated in any way. Here we discuss how grouped approaches to icEEG overcome challenges related to sparse-sampling, correct for individual variations in response and provide statistically valid models of brain activity in a population. By the generation of whole-brain activity maps, grouped icEEG enables the study of intra and interregional dynamics between distributed cortical substrates exhibiting task-dependent activity. In this fashion, grouped icEEG analyses can provide significant advances in understanding the mechanisms by which cortical networks give rise to cognitive functions. PMID- 26257674 TI - Higher chronic stress is associated with a decrease in temporal sensitivity but not in subjective duration in healthy young men. AB - Maintaining accurate and precise temporal perception under conditions of stress is important. Studies in animal models and clinic patients have suggested that time perception can change under chronic stress. Little is known, however, about the relationship between chronic stress and time perception in healthy individuals. Here, a sample of 62 healthy young men completed Cohen's Perceived Stress Scale (PSS) as a measure of chronic stress levels, while time perception was measured using a temporal bisection task. This task used short (400 ms) and long (1600 ms) visual signals as anchor durations. Participants were presented with a range of intermediate probe durations and were required to judge whether the durations were more similar to the short or the long anchor. Results showed that chronic stress was negatively related to temporal sensitivity indexed by the Weber ratio. However, there was no significant correlation between chronic stress and subjective duration indexed by the bisection point. These results demonstrate that higher chronic stress is associated with lower temporal sensitivity and thus provide evidence for a link between chronic stress and time perception in healthy adults. PMID- 26257675 TI - Hesitant avoidance while walking: an error of social behavior generated by mutual interaction. AB - Altering physical actions when responding to changing environmental demands is important but not always effectively performed. This ineffectiveness, which is an error of social behavior generated by mutual interactions, is not well understood. This study investigated mechanisms of a hesitant behavior that occurs in people walking toward each other, causing people to move in the same direction when attempting to avoid a collision. Using a motion capture device affixed to 17 pairs, we first confirmed the hesitant behavior by a difference between the experimental task, which involved an indeterminate situation to assess the actions of another individual, and the control task, which involved a predetermined avoiding direction, in a real-time situation involving two people. We next investigated the effect of three external factors: long distance until an event, synchronized walking cycle, and different foot relations in dyads on the hesitant behavior. A dramatic increase in freezing and near-collision behavior occurred in dyads for which the avoiding direction was not predetermined. The behavior related with the combination of long distance until an event, synchronized walking cycle, and different foot relations in dyads. We found that the hesitant behavior is influenced by an interpersonal relationship under enough distance to predict other movement. The hesitant behavior has possibly emerged as an undesired by-product of joint action. These results contribute to our understanding of the mechanisms of adaptive control of perception-action coupling in mutual interaction. PMID- 26257676 TI - Using Motivational Interviewing to reduce threats in conversations about environmental behavior. AB - Human behavior contributes to a waste of environmental resources and our society is looking for ways to reduce this problem. However, humans may perceive feedback about their environmental behavior as threatening. According to self determination theory (SDT), threats decrease intrinsic motivation for behavior change. According to self-affirmation theory (SAT), threats can harm individuals' self-integrity. Therefore, individuals should show self-defensive biases, e.g., in terms of presenting counter-arguments when presented with environmental behavior change. The current study examines how change recipients respond to threats from change agents in interactions about environmental behavior change. Moreover, we investigate how Motivational Interviewing (MI) - an intervention aimed at increasing intrinsic motivation - can reduce threats at both the social and cognitive level. We videotaped 68 dyadic interactions with change agents who either did or did not use MI (control group). We coded agents verbal threats and recipients' verbal expressions of motivation. Recipients also rated agents' level of confrontation and empathy (i.e., cognitive reactions). As hypothesized, threats were significantly lower when change agents used MI. Perceived confrontations converged with observable social behavior of change agents in both groups. Moreover, behavioral threats showed a negative association with change recipients' expressed motivation (i.e., reasons to change). Contrary to our expectations, we found no relation between change agents' verbal threats and change recipients' verbally expressed self-defenses (i.e., sustain talk). Our results imply that MI reduces the adverse impact of threats in conversations about environmental behavior change on both the social and cognitive level. We discuss theoretical implications of our study in the context of SAT and SDT and suggest practical implications for environmental change agents in organizations. PMID- 26257677 TI - Look together: analyzing gaze coordination with epistemic network analysis. AB - When conversing and collaborating in everyday situations, people naturally and interactively align their behaviors with each other across various communication channels, including speech, gesture, posture, and gaze. Having access to a partner's referential gaze behavior has been shown to be particularly important in achieving collaborative outcomes, but the process in which people's gaze behaviors unfold over the course of an interaction and become tightly coordinated is not well understood. In this paper, we present work to develop a deeper and more nuanced understanding of coordinated referential gaze in collaborating dyads. We recruited 13 dyads to participate in a collaborative sandwich-making task and used dual mobile eye tracking to synchronously record each participant's gaze behavior. We used a relatively new analysis technique-epistemic network analysis-to jointly model the gaze behaviors of both conversational participants. In this analysis, network nodes represent gaze targets for each participant, and edge strengths convey the likelihood of simultaneous gaze to the connected target nodes during a given time-slice. We divided collaborative task sequences into discrete phases to examine how the networks of shared gaze evolved over longer time windows. We conducted three separate analyses of the data to reveal (1) properties and patterns of how gaze coordination unfolds throughout an interaction sequence, (2) optimal time lags of gaze alignment within a dyad at different phases of the interaction, and (3) differences in gaze coordination patterns for interaction sequences that lead to breakdowns and repairs. In addition to contributing to the growing body of knowledge on the coordination of gaze behaviors in joint activities, this work has implications for the design of future technologies that engage in situated interactions with human users. PMID- 26257678 TI - Common impairments of emotional facial expression recognition in schizophrenia across French and Japanese cultures. AB - To address whether the recognition of emotional facial expressions is impaired in schizophrenia across different cultures, patients with schizophrenia and age matched normal controls in France and Japan were tested with a labeling task of emotional facial expressions and a matching task of unfamiliar faces. Schizophrenia patients in both France and Japan were less accurate in labeling fearful facial expressions. There was no correlation between the scores of facial emotion labeling and face matching. These results suggest that the impaired recognition of emotional facial expressions in schizophrenia is common across different cultures. PMID- 26257679 TI - Embodied cognitive flexibility and neuroplasticity following Quadrato Motor Training. AB - Quadrato Motor Training (QMT) is a whole-body movement contemplative practice aimed at increasing health and well-being. Previous research studying the effect of one QMT session suggested that one of its means for promoting health is by enhancing cognitive flexibility, an important dimension of creativity. Yet, little is known about the effect of a longer QMT practice on creativity, or the relative contribution of the cognitive and motor aspects of the training. Here, we continue this line of research in two inter-related studies, examining the effects of prolonged QMT. In the first, we investigated the effect of 4-weeks of daily QMT on creativity using the Alternate Uses (AUs) Task. In order to determine whether changes in creativity were driven by the cognitive or the motor aspects of the training, we used two control groups: Verbal Training (VT, identical cognitive training with verbal response) and Simple Motor Training (SMT, similar motor training with reduced choice requirements). Twenty-seven participants were randomly assigned to one of the groups. Following training, cognitive flexibility significantly increased in the QMT group, which was not the case for either the SMT or VT groups. In contrast to one QMT session, ideational fluency was also significantly increased. In the second study, we conducted a pilot longitudinal structural magnetic resonance imaging and diffusion tensor imaging (4-weeks QMT). We report gray matter volume and fractional anisotropy changes, in several regions, including the cerebellum, previously related to interoceptive accuracy. The anatomical changes were positively correlated with cognitive flexibility scores. Albeit the small sample size and preliminary nature of the findings, these results provide support for the hypothesized creativity motor connection. The results are compared to other contemplative studies, and discussed in light of theoretical models integrating cognitive flexibility, embodiment and the motor system. PMID- 26257680 TI - Mentalization, attachment, and subjective identity. PMID- 26257681 TI - True gender ratios and stereotype rating norms. AB - We present a study comparing, in English, perceived distributions of men and women in 422 named occupations with actual real world distributions. The first set of data was obtained from previous a large-scale norming study, whereas the second set was mostly drawn from UK governmental sources. In total, real world ratios for 290 occupations were obtained for our perceive vs. real world comparison, of which 205 were deemed to be unproblematic. The means for the two sources were similar and the correlation between them was high, suggesting that people are generally accurate at judging real gender ratios, though there were some notable exceptions. Beside this correlation, some interesting patterns emerged from the two sources, suggesting some response strategies when people complete norming studies. We discuss these patterns in terms of the way real world data might complement norming studies in determining gender stereotypicality. PMID- 26257682 TI - Lagged and instantaneous dynamical influences related to brain structural connectivity. AB - Contemporary neuroimaging methods can shed light on the basis of human neural and cognitive specializations, with important implications for neuroscience and medicine. Indeed, different MRI acquisitions provide different brain networks at the macroscale; whilst diffusion-weighted MRI (dMRI) provides a structural connectivity (SC) coincident with the bundles of parallel fibers between brain areas, functional MRI (fMRI) accounts for the variations in the blood-oxygenation level-dependent T2(*) signal, providing functional connectivity (FC). Understanding the precise relation between FC and SC, that is, between brain dynamics and structure, is still a challenge for neuroscience. To investigate this problem, we acquired data at rest and built the corresponding SC (with matrix elements corresponding to the fiber number between brain areas) to be compared with FC connectivity matrices obtained by three different methods: directed dependencies by an exploratory version of structural equation modeling (eSEM), linear correlations (C) and partial correlations (PC). We also considered the possibility of using lagged correlations in time series; in particular, we compared a lagged version of eSEM and Granger causality (GC). Our results were two-fold: firstly, eSEM performance in correlating with SC was comparable to those obtained from C and PC, but eSEM (not C, nor PC) provides information about directionality of the functional interactions. Second, interactions on a time scale much smaller than the sampling time, captured by instantaneous connectivity methods, are much more related to SC than slow directed influences captured by the lagged analysis. Indeed the performance in correlating with SC was much worse for GC and for the lagged version of eSEM. We expect these results to supply further insights to the interplay between SC and functional patterns, an important issue in the study of brain physiology and function. PMID- 26257683 TI - The influence of element type and crossed relation on the difficulty of chunk decomposition. AB - Chunk decomposition is an aspect of problem solving that involves decomposing a pattern into its component parts in order to regroup them into a new pattern. Previous work suggests that the primary source of difficulty in chunk decomposition is whether a problem's solution requires removing a part that is a meaningful perceptual pattern (termed a chunk) or not (a non-chunk). However, the role of spatial overlap (crossed relation or not) has been ignored in this line of research. Here, we dissociated the role of element type and crossed relation in chunk decomposition problems by employing a Chinese character transformation task. We replicated the finding that when the to-be-removed element is a non chunk, the problem is more difficult to solve than when the element is a chunk. However, this result held only if the elements had no crossed relation. Relative to non-crossed relation, problems that involved removing elements that overlapped with the remaining character were more difficult to solve irrespective of the element type. We conclude that both element type and crossed relation can cause the difficulty of chunk decomposition and crossed relation plays more important role in preventing people from finding insightful ways to decompose chunk relative to element type. PMID- 26257684 TI - Increased reward value of non-social stimuli in children and adolescents with autism. AB - An econometric choice task was used to estimate the implicit reward value of social and non-social stimuli related to restricted interests in children and adolescents with (n = 12) and without (n = 22) autism spectrum disorder (ASD). Mixed effects logistic regression analyses revealed that groups differed in valuation of images related to restricted interests: control children were indifferent to cash payouts to view these images, but children with ASD were willing to receive less cash payout to view these images. Groups did not differ in valuation of social images or non-social images not related to restricted interests. Results highlight that motivational accounts of ASD should also consider the reward value of non-social stimuli related to restricted interests in ASD (Dichter and Adolphs, 2012). PMID- 26257685 TI - A multi-method exploratory study of stress, coping, and substance use among high school youth in private schools. AB - There is growing awareness that students' experiences of stress may impede academic success, compromise mental health, and promote substance use. We examined these factors in an under-studied population, private/independent high school students, using a multi-method (qualitative and quantitative), iterative data collection and analytic process. We first conducted qualitative interviews with faculty and staff at a number of highly competitive private schools, followed by an anonymous quantitative survey with 128 11th grade students from two of these settings. We then conducted a qualitative exploration of the quantitative results with a subset of students. Next, a set of Expert Panel members participated in qualitative interviews to reflect on and interpret study findings. Overall, we found students experienced high levels of chronic stress, particularly in relation to academic performance and the college admissions process. While students described a range of effective, adaptive coping strategies, they also commonly internalized these serious pressures and turned to alcohol and drugs to cope with chronic stress, although not typically at problematic levels. We discuss study implications for both schools and families derived from the Expert Panel. PMID- 26257686 TI - Early warning for human mental sub-health based on fMRI data analysis: an example from a seafarers' resting-data study. AB - Effective mental sub-health early warning mechanism is of great significance in the protection of individual mental health. The traditional mental health assessment method is mainly based on questionnaire surveys, which may have some uncertainties. In this study, based on the relationship between the default mode network (DMN) and the mental health status, we proposed a human mental sub-health early warning method by utilizing two-fold support vector machine (SVM) model, where seafarers' fMRI data analysis was utilized as an example. The method firstly constructed a structural-functional DMN template by combining the anatomical automatic labeling template with the functional DMN extracted by independent component analysis. Then, it put forward a two-fold SVM-based classifier, with one-class SVM utilized for the training of the initial classifier and two-class SVM utilized to refine the classification performance, to identify seafarers' mental health status by utilizing the correlation coefficients (CCs) among the areas of structural-functional DMN as the features. The experimental results showed that the proposed model could discriminate the seafarers with DMN function alteration from the healthy control (HC) effectively, and further the results demonstrated that when compared with the HC group, the brain functional disorders of the mental sub-healthy seafarers mainly manifested as follows: the functional connectivity of DMN had obvious alteration; the CCs among the different DMN regions were significant lower; the regional homogeneity decreased in parts of the prefrontal cortex and increased in multi-regions of the parietal, temporal and occipital cortices; the fractional amplitude of low frequency fluctuation decreased in parts of the prefrontal cortex and increased in parts of the parietal cortex. All of the results showed that fMRI-based analysis of brain functional activities could be effectively used to distinguish the mental health and sub-health status. PMID- 26257687 TI - Manipulation gesture effect in visual and auditory presentations: the link between tools in perceptual and motor tasks. AB - There is much behavioral and neurophysiological evidence in support of the idea that seeing a tool activates motor components of action related to the perceived object (e.g., grasping, use manipulation). However, the question remains as to whether the processing of the motor components associated with the tool is automatic or depends on the situation, including the task and the modality of tool presentation. The present study investigated whether the activation of motor components involved in tool use in response to the simple perception of a tool is influenced by the link between prime and target tools, as well as by the modality of presentation, in perceptual or motor tasks. To explore this issue, we manipulated the similarity of gesture involved in the use of the prime and target (identical, similar, different) with two tool presentation modalities of the presentation tool (visual or auditory) in perceptual and motor tasks. Across the experiments, we also manipulated the relevance of the prime (i.e., associated or not with the current task). The participants saw a first tool (or heard the sound it makes), which was immediately followed by a second tool on which they had to perform a perceptual task (i.e., indicate whether the second tool was identical to or different from the first tool) or a motor task (i.e., manipulate the second tool as if it were the first tool). In both tasks, the similarity between the gestures employed for the first and the second tool was manipulated (Identical, Similar or Different gestures). The results showed that responses were faster when the manipulation gestures for the two tools were identical or similar, but only in the motor task. This effect was observed irrespective of the modality of presentation of the first tool, i.e., visual or auditory. We suggest that the influence of manipulation gesture on response time depends on the relevance of the first tool in motor tasks. We discuss these motor activation results in terms of the relevance and demands of the tasks. PMID- 26257688 TI - Do-gooder derogation in children: the social costs of generosity. AB - Generosity is greatly valued and admired, but can it sometimes be unappealing? The current study investigated 8- to 10-year-old children's (N = 128) preference for generous individuals, and the effects of social comparison on their preferences. In Experiment 1, children showed a strong preference for a generous to a stingy child; however, this preference was significantly reduced in a situation that afforded children a comparison of their own (lesser) generosity to that of another child. In Experiment 2, children's liking for a generous individual was not reduced when that individual was an adult, suggesting that similarity in age influences whether a child engages in social comparison. These findings indicate that, by middle childhood, coming up short in comparison with a peer can decrease one's liking for a generous individual. PMID- 26257689 TI - Commentary: "Poverty impedes cognitive function" and "The poor's poor mental power". PMID- 26257690 TI - Longer prime presentation decreases picture-word cross-domain priming. AB - A short prime presentation has been shown to provide a greater priming magnitude, whereas a longer prime presentation results in a lower priming magnitude. In Experiment 1, we attempted to replicate the decrease of priming using word stimuli. Words were presented in both prime and test sessions, and participants judged whether each stimulus was natural or manmade. In Experiment 2, we employed a cross-domain priming paradigm to assess the impact of prime duration on non perceptual processes. Pictures were presented in prime sessions, and their semantically matched words were presented in test sessions. We did not observe a significant decrease in priming in Experiment 1. However, we found that 2000 ms of prime exposure led to weaker cross-domain priming when compared with 250 ms of the exposure in Experiment 2. The results suggest that the longer presentation of pictures causes a non-perceptual adaptation effect. This effect may occur at conceptual, linguistic, and/or response-related levels. PMID- 26257692 TI - Sharing feelings online: studying emotional well-being via automated text analysis of Facebook posts. AB - Digital traces of activity on social network sites represent a vast source of ecological data with potential connections with individual behavioral and psychological characteristics. The present study investigates the relationship between user-generated textual content shared on Facebook and emotional well being. Self-report measures of depression, anxiety, and stress were collected from 201 adult Facebook users from North Italy. Emotion-related textual indicators, including emoticon use, were extracted form users' Facebook posts via automated text analysis. Correlation analyses revealed that individuals with higher levels of depression, anxiety expressed negative emotions on Facebook more frequently. In addition, use of emoticons expressing positive emotions correlated negatively with stress level. When comparing age groups, younger users reported higher frequency of both emotion-related words and emoticon use in their posts. Also, the relationship between online emotional expression and self-report emotional well-being was generally stronger in the younger group. Overall, findings support the feasibility and validity of studying individual emotional well-being by means of examination of Facebook profiles. Implications for online screening purposes and future research directions are discussed. PMID- 26257691 TI - Sex-dependent effects on tasks assessing reinforcement learning and interference inhibition. AB - Increasing evidence suggests that the prefrontal cortex (PFC) is influenced by sex steroids and that some cognitive functions dependent on the PFC may be sexually differentiated in humans. Past work has identified a male advantage on certain complex reinforcement learning tasks, but it is unclear which latent task components are important to elicit the sex difference. The objective of the current study was to investigate whether there are sex differences on measures of response inhibition and valenced feedback processing, elements that are shared by previously studied reinforcement learning tasks. Healthy young adults (90 males, 86 females) matched in general intelligence completed the Probabilistic Selection Task (PST), a Simon task, and the Stop-Signal task. On the PST, females were more accurate than males in learning from positive (but not negative) feedback. On the Simon task, males were faster than females, especially in the face of incongruent stimuli. No sex difference was observed in Stop-Signal reaction time. The current findings provide preliminary support for a sex difference in the processing of valenced feedback and in interference inhibition. PMID- 26257693 TI - Evolved biocultural beings (who invented computers). PMID- 26257694 TI - Using gaze patterns to predict task intent in collaboration. AB - In everyday interactions, humans naturally exhibit behavioral cues, such as gaze and head movements, that signal their intentions while interpreting the behavioral cues of others to predict their intentions. Such intention prediction enables each partner to adapt their behaviors to the intent of others, serving a critical role in joint action where parties work together to achieve a common goal. Among behavioral cues, eye gaze is particularly important in understanding a person's attention and intention. In this work, we seek to quantify how gaze patterns may indicate a person's intention. Our investigation was contextualized in a dyadic sandwich-making scenario in which a "worker" prepared a sandwich by adding ingredients requested by a "customer." In this context, we investigated the extent to which the customers' gaze cues serve as predictors of which ingredients they intend to request. Predictive features were derived to represent characteristics of the customers' gaze patterns. We developed a support vector machine-based (SVM-based) model that achieved 76% accuracy in predicting the customers' intended requests based solely on gaze features. Moreover, the predictor made correct predictions approximately 1.8 s before the spoken request from the customer. We further analyzed several episodes of interactions from our data to develop a deeper understanding of the scenarios where our predictor succeeded and failed in making correct predictions. These analyses revealed additional gaze patterns that may be leveraged to improve intention prediction. This work highlights gaze cues as a significant resource for understanding human intentions and informs the design of real-time recognizers of user intention for intelligent systems, such as assistive robots and ubiquitous devices, that may enable more complex capabilities and improved user experience. PMID- 26257696 TI - Mechanisms behind the testing effect: an empirical investigation of retrieval practice in meaningful learning. AB - The testing effect-more learning by testing as compared to restudying-is a well established finding. A typical testing procedure in the context of meaningful learning comprises a recall task after an initial study phase. Different theories refer to different mechanisms when explaining the positive effects of such recall tasks. In the context of learning from expository texts, we tested three mechanisms as suggested by a variety of prominent approaches: the elaborative retrieval theory, the theory of transfer-appropriate processing, and the unspecific-goal perspective. We experimentally varied the type of testing task (short-answer task vs. free-recall task, both compared to a restudy task) in a within-subject design (N = 47 university students). We replicated the testing effect. We found no evidence for a transfer-appropriate processing effect or an unspecific-goal effect. The testing effect disappeared when statistically controlling for mental effort. Initially non-tested material was also fostered by testing (spreading activation effect). These findings indicate that testing helps learning when learners must invest substantial mental effort, as suggested by the elaborative retrieval theory. For educational purposes, testing tasks should be assigned that require the learners to invest substantial mental effort. PMID- 26257695 TI - Music reduces pain and increases resting state fMRI BOLD signal amplitude in the left angular gyrus in fibromyalgia patients. AB - Music reduces pain in fibromyalgia (FM), a chronic pain disease, but the functional neural correlates of music-induced analgesia (MIA) are still largely unknown. We recruited FM patients (n = 22) who listened to their preferred relaxing music and an auditory control (pink noise) for 5 min without external noise from fMRI image acquisition. Resting state fMRI was then acquired before and after the music and control conditions. A significant increase in the amplitude of low frequency fluctuations of the BOLD signal was evident in the left angular gyrus (lAnG) after listening to music, which in turn, correlated to the analgesia reports. The post-hoc seed-based functional connectivity analysis of the lAnG showed found higher connectivity after listening to music with right dorsolateral prefrontal cortex (rdlPFC), the left caudate (lCau), and decreased connectivity with right anterior cingulate cortex (rACC), right supplementary motor area (rSMA), precuneus and right precentral gyrus (rPreG). Pain intensity (PI) analgesia was correlated (r = 0.61) to the connectivity of the lAnG with the rPreG. Our results show that MIA in FM is related to top-down regulation of the pain modulatory network by the default mode network (DMN). PMID- 26257697 TI - Educational games for brain health: revealing their unexplored potential through a neurocognitive approach. AB - Educational games link the motivational nature of games with learning of knowledge and skills. Here, we go beyond effects on these learning outcomes. We review two lines of evidence which indicate the currently unexplored potential of educational games to promote brain health: First, gaming with specific neurocognitive demands (e.g., executive control), and second, educational learning experiences (e.g., studying foreign languages) improve brain health markers. These markers include cognitive ability, brain function, and brain structure. As educational games allow the combination of specific neurocognitive demands with educational learning experiences, they seem to be optimally suited for promoting brain health. We propose a neurocognitive approach to reveal this unexplored potential of educational games in future research. PMID- 26257698 TI - Epistemic motivation affects the processing of negative emotional stimuli in interpersonal decisions. AB - The present electrophysiological study investigated the role of the need for cognitive closure (NFC) in emotional processing. The NFC is conceptualized as an epistemic motive that is related to how and why people seek out information in social environments. Event-related potentials were recorded while individuals with high NFC (i.e., low epistemic motivation) or low NFC (i.e., high epistemic motivation) performed a modified Ultimatum Game, in which the emotions of happy or angry game agents were employed to predict their most likely offer. High-NFC participants more closely adhered to the decisions rules of the game than low-NFC individuals did. The electrophysiological results showed that the dispositional NFC modified early perceptual components (N170, N200, and P200). The potentials showed that high-NFC subjects had a processing bias to angry faces, whereas low NFC individuals exhibited no such effects. These findings indicated that high-NFC individuals were more sensitive to negative emotional stimuli than low-NFC individuals in an interpersonal decision-making task. PMID- 26257699 TI - Abnormal emotion processing, but intact fairness and intentionality considerations during social decision-making in schizophrenia. AB - Schizophrenia is a severe mental disorder that is highly characterized by social cognitive impairments. Most studies investigating these impairments focus on one specific social domain such as emotion recognition. However, in daily life, processing complex social situations relies on the combination of several social cognitive and affective processes simultaneously rather than one process alone. A modified version of the economically based Ultimatum Game was used to measure the interplay between fairness, intentionality, and emotion considerations during social decision-making. In this task, participants accept or reject fair and unfair monetary offers proposed intentionally or unintentionally by either angry, happy, neutral, or sad proposers. Behavioral data was collected from a group of schizophrenia patients (N = 35) and a group of healthy individuals (N = 30). Like healthy participants, schizophrenia patients differentiated between fair and unfair offers by rejecting unfair offers more compared to fair offers. However, overall patients did reject more fair offers, indicating that their construct of fairness operates within different margins. In both groups, intentional unfair offers were rejected more compared to unintentional ones, indicating a normal integration of intentionality considerations in schizophrenia. Importantly, healthy subjects also differentiated between proposers' emotion when rejecting unfair offers (more rejections from proposers depicting angry faces compared to proposers depicting, happy, neutral, or sad faces). Schizophrenia patients' decision behavior on the other hand, was not affected by the proposers' emotions. The current study thus shows that schizophrenia patients have specific problems with processing and integrating emotional information. Importantly, the finding that patients display normal fairness and intentionality considerations emphasizes preservation of central social cognitive processes in schizophrenia. PMID- 26257700 TI - Calm and smart? A selective review of meditation effects on decision making. AB - Over the past two decades, there has been a growing interest in the use of meditation to improve cognitive performance, emotional balance, and well-being. As a consequence, research into the psychological effects and neural mechanisms of meditation has been accumulating. Whether and how meditation affects decision making is not yet clear. Here, we review evidence from behavioral and neuroimaging studies and summarize the effects of meditation on social and non social economic decision making. Research suggests that meditation modulates brain activities associated with cognitive control, emotion regulation and empathy, and leads to improved non-social and social decision making. Accordingly, we propose an integrative model in which cognitive control, emotional regulation, and empathic concern mediate the effects of meditation on decision making. This model provides insights into the mechanisms by which meditation affects the decision making process. More evidence is needed to test our explanatory model and to explore the function of specific brain areas and their interactive effects on decision making during meditation training. PMID- 26257701 TI - Contribution of working memory in multiplication fact network in children may shift from verbal to visuo-spatial: a longitudinal investigation. AB - Number facts are commonly assumed to be verbally stored in an associative multiplication fact retrieval network. Prominent evidence for this assumption comes from so-called operand-related errors (e.g., 4 * 6 = 28). However, little is known about the development of this network in children and its relation to verbal and non-verbal memories. In a longitudinal design, we explored elementary school children from grades 3 and 4 in a multiplication verification task with the operand-related and -unrelated distractors. We examined the contribution of multiplicative fact retrieval by verbal and visuo-spatial short-term and working memory (WM). Children in grade 4 showed smaller reaction times in all conditions. However, there was no significant difference in errors between grades. Contribution of verbal and visuo-spatial WM also changed with grade. Multiplication correlated with verbal WM and performance in grade 3 but with visuo-spatial WM and performance in grade 4. We suggest that the relation to verbal WM in grade 3 indicates primary linguistic learning of and access to multiplication in grade 3 which is probably based on verbal repetition of the multiplication table heavily practiced in grades 2 and 3. However, the relation to visuo-spatial semantic WM in grade 4 suggests that there is a shift from verbal to visual and semantic learning in grade 4. This shifting may be induced because later in elementary school, multiplication problems are rather carried out via more written, i.e., visual tasks, which also involve executive functions. More generally, the current data indicates that mathematical development is not generally characterized by a steady progress in performance; rather verbal and non-verbal memory contributions of performance shift over time, probably due to different learning contents. PMID- 26257703 TI - DEC2-E4BP4 Heterodimer Represses the Transcriptional Enhancer Activity of the EE Element in the Per2 Promoter. AB - The circadian oscillation of clock gene expression in mammals is based on the interconnected transcriptional/translational feedback loops of Period (Per) and Bmal1. The Per feedback loop initiates transcription through direct binding of the BMAL1-CLOCK (NPAS2) heterodimer to the E-box of the Per2 promoter region. Negative feedback of PER protein on this promoter subsequently represses transcription. Other circadian transcription regulators, particularly E4BP4 and DEC2, regulate the amplitude and phase of Per2 expression rhythms. Moreover, a direct repeat of E-box-like (EE) elements in the Per2 promoter is required for its cell-autonomous circadian rhythm. However, the detailed mechanism for repression of the two core sequences of the EE element in the Per2 promoter region is unknown. Here, we show that E4BP4 binds to the Per2 EE element with DEC2 to repress transcription and identify the DEC2-E4BP4 heterodimer as a key repressor of the tightly interlocked Per2 feedback loop in the mammalian circadian oscillator. Our results suggest an additional modulatory mechanism for tuning of the phase of cell-autonomous Per2 gene expression cycling. PMID- 26257704 TI - Estetrol Modulates Endothelial Nitric Oxide Synthesis in Human Endothelial Cells. AB - Estetrol (E4) is a natural human estrogen that is present at high concentrations during pregnancy. E4 has been reported to act as an endogenous estrogen receptor modulator, exerting estrogenic actions on the endometrium or the central nervous system but presenting antagonistic effects on the breast. Due to these characteristics, E4 is currently being developed for a number of clinical applications, including contraception and menopausal hormone therapy. Endothelial nitric oxide (NO) is a key player for vascular function and disease during pregnancy and throughout aging in women. Endothelial NO is an established target of estrogens that enhance its formation in human endothelial cells. We here addressed the effects of E4 on the activity and expression of the endothelial nitric oxide synthase (eNOS) in cultured human umbilical vein endothelial cells (HUVEC). E4 stimulated the activation of eNOS and NO secretion in HUVEC. E4 was significantly less effective compared to E2, and a peculiar concentration dependent effect was found, with higher amounts of E4 being less effective than lower concentrations. When E2 was combined with E4, an interesting pattern was noted. E4 antagonized NO synthesis induced by pregnancy-like E2 concentrations. However, E4 did not impede the modest induction of NO synthesis associated with postmenopausal-like E2 levels. These results support the hypothesis that E4 may be a regulator of NO synthesis in endothelial cells and raise questions on its peculiar signaling in this context. Our results may be useful to interpret the role of E4 during human pregnancy and possibly to help develop this interesting steroid for clinical use. PMID- 26257702 TI - The Dark Side of the Force - Constraints and Complications of Cell Therapies for Stroke. AB - Cell therapies are increasingly recognized as a promising option to augment the limited therapeutic arsenal available to fight ischemic stroke. During the last two decades, cumulating preclinical evidence has indicated a substantial efficacy for most cell treatment paradigms and first clinical trials are currently underway to assess safety and feasibility in patients. However, the strong and still unmet demand for novel stroke treatment options and exciting findings reported from experimental studies may have drawn our attention away from potential side effects related to cell therapies and the ways by which they are commonly applied. This review summarizes common and less frequent adverse events that have been discovered in preclinical and clinical investigations assessing cell therapies for stroke. Such adverse events range from immunological and neoplastic complications over seizures to cell clotting and cell-induced embolism. It also describes potential complications of clinically applicable administration procedures, detrimental interactions between therapeutic cells, and the pathophysiological environment that they are placed into, as well as problems related to cell manufacturing. Virtually each therapeutic intervention comes at a certain risk for complications. Side effects do therefore not generally compromise the value of cell treatments for stroke, but underestimating such complications might severely limit therapeutic safety and efficacy of cell treatment protocols currently under development. On the other hand, a better understanding will provide opportunities to further improve existing therapeutic strategies and might help to define those circumstances, under which an optimal effect can be realized. Hence, the review eventually discusses strategies and recommendations allowing us to prevent or at least balance potential complications in order to ensure the maximum therapeutic benefit at minimum risk for stroke patients. PMID- 26257705 TI - Gut Melatonin in Vertebrates: Chronobiology and Physiology. AB - Melatonin, following discovery in the bovine pineal gland, has been detected in several extra-pineal sources including gastrointestinal tract or gut. Arylalkylamine N-acetyltransferase (AANAT) is the key regulator of its biosynthesis. Melatonin in pineal is rhythmically produced with a nocturnal peak in synchronization with environmental light-dark cycle. A recent study on carp reported first that melatonin levels and intensity of a ~23 kDa AANAT protein in each gut segment also exhibit significant daily variations but, unlike pineal, show a peak at midday in all seasons. Extensive experimental studies ruled out direct role of light-dark conditions in determining temporal pattern of gut melatoninergic system in carp, and opened up possible role of environmental non photic cue(s) as its synchronizer. Based on mammalian findings, physiological significance of gut-derived melatonin also appears unique because its actions at local levels sharing paracrine and/or autocrine functions have been emphasized. The purpose of this mini review is to summarize the existing data on the chronobiology and physiology of gut melatonin and to emphasize their relation with the same hormone derived in the pineal in vertebrates including fish. PMID- 26257707 TI - Microbially induced corrosion of carbon steel in deep groundwater environment. AB - The metallic low and intermediate level radioactive waste generally consists of carbon steel and stainless steels. The corrosion rate of carbon steel in deep groundwater is typically low, unless the water is very acidic or microbial activity in the environment is high. Therefore, the assessment of microbially induced corrosion of carbon steel in deep bedrock environment has become important for evaluating the safety of disposal of radioactive waste. Here we studied the corrosion inducing ability of indigenous microbial community from a deep bedrock aquifer. Carbon steel coupons were exposed to anoxic groundwater from repository site 100 m depth (Olkiluoto, Finland) for periods of 3 and 8 months. The experiments were conducted at both in situ temperature and room temperature to investigate the response of microbial population to elevated temperature. Our results demonstrate that microorganisms from the deep bedrock aquifer benefit from carbon steel introduced to the nutrient poor anoxic deep groundwater environment. In the groundwater incubated with carbon steel the planktonic microbial community was more diverse and 100-fold more abundant compared to the environment without carbon steel. The betaproteobacteria were the most dominant bacterial class in all samples where carbon steel was present, whereas in groundwater incubated without carbon steel the microbial community had clearly less diversity. Microorganisms induced pitting corrosion and were found to cluster inside the corrosion pits. Temperature had an effect on the species composition of microbial community and also affected the corrosion deposits layer formed on the surface of carbon steel. PMID- 26257706 TI - Sestrin2, a Regulator of Thermogenesis and Mitohormesis in Brown Adipose Tissue. AB - Sestrin2 is a stress-inducible protein that functions as an antioxidant and inhibitor of mTOR complex 1. In a recent study, we found that Sestrin2 overexpression in brown adipocytes interfered with normal metabolism by reducing mitochondrial respiration through the suppression of uncoupling protein 1 (UCP1) expression. The metabolic effects of Sestrin2 in brown adipocytes were dependent on its antioxidant activity, and chemical antioxidants produced similar effects in inhibiting UCP1-dependent thermogenesis. These observations suggest that low levels of reactive oxygen species (ROS) in brown adipocytes can actually be beneficial and necessary for proper metabolic homeostasis. In addition, considering that Sestrins are ROS inducible and perform ROS detoxifying as well as other metabolism-controlling functions, they are potential regulators of mitohormesis. This is a concept in which overall beneficial effects result from low-level oxidative stress stimuli, such as the ones induced by caloric restriction or physical exercise. In this perspective, we incorporate our recent insight obtained from the Sestrin2 study toward a better understanding of the relationship between ROS, Sestrin2, and mitochondrial metabolism in the context of brown adipocyte physiology. PMID- 26257708 TI - Progress in the development of gelling agents for improved culturability of microorganisms. AB - Gelling agents are required for formulating both solid and semisolid media, vital for the isolation of microorganisms. Gelatin was the first gelling agent to be discovered but it soon paved the way for agar, which has far superior material qualities. Source depletion, issues with polymerase-chain-reaction and inability to sustain extermophiles etc., necessitate the need of other gelling agents. Many new gelling agents, such as xantham gum, gellan gum, carrageenan, isubgol, and guar gum have been formulated, raising the hopes for the growth of previously unculturable microorganisms. We evaluate the progress in the development of gelling agents, with the hope that our synthesis would help accelerate research in the field. PMID- 26257709 TI - The reduced genomes of Parcubacteria (OD1) contain signatures of a symbiotic lifestyle. AB - Candidate phylum OD1 bacteria (also referred to as Parcubacteria) have been identified in a broad range of anoxic environments through community survey analysis. Although none of these species have been isolated in the laboratory, several genome sequences have been reconstructed from metagenomic sequence data and single-cell sequencing. The organisms have small (generally <1 Mb) genomes with severely reduced metabolic capabilities. We have reconstructed 8 partial to near-complete OD1 genomes from oxic groundwater samples, and compared them against existing genomic data. The conserved core gene set comprises 202 genes, or ~28% of the genomic complement. "Housekeeping" genes and genes for biosynthesis of peptidoglycan and Type IV pilus production are conserved. Gene sets for biosynthesis of cofactors, amino acids, nucleotides, and fatty acids are absent entirely or greatly reduced. The only aspects of energy metabolism conserved are the non-oxidative branch of the pentose-phosphate shunt and central glycolysis. These organisms also lack some activities conserved in almost all other known bacterial genomes, including signal recognition particle, pseudouridine synthase A, and FAD synthase. Pan-genome analysis indicates a broad genotypic diversity and perhaps a highly fluid gene complement, indicating historical adaptation to a wide range of growth environments and a high degree of specialization. The genomes were examined for signatures suggesting either a free living, streamlined lifestyle, or a symbiotic lifestyle. The lack of biosynthetic capabilities and DNA repair, along with the presence of potential attachment and adhesion proteins suggest that the Parcubacteria are ectosymbionts or parasites of other organisms. The wide diversity of genes that potentially mediate cell cell contact suggests a broad range of partner/prey organisms across the phylum. PMID- 26257710 TI - Combatting cyanobacteria with hydrogen peroxide: a laboratory study on the consequences for phytoplankton community and diversity. AB - Experiments with different phytoplankton densities in lake samples showed that a high biomass increases the rate of hydrogen peroxide (HP) degradation and decreases the effectiveness of HP in the selective suppression of dominant cyanobacteria. However, selective application of HP requires usage of low doses only, accordingly this defines the limits for use in lake mitigation. To acquire insight into the impact of HP on other phytoplankton species, we have followed the succession of three phytoplankton groups in lake samples that were treated with different concentrations of HP using a taxa-specific fluorescence emission test. This fast assay reports relatively well on coarse changes in the phytoplankton community; the measured data and the counts from microscopical analysis of the phytoplankton matched quite well. The test was used to pursue HP application in a Planktothrix agardhii-dominated lake sample and displayed a promising shift in the phytoplankton community in only a few weeks. From a low diversity community, a change to a status with a significantly higher diversity and increased abundance of eukaryotic phytoplankton species was established. Experiments in which treated samples were re-inoculated with original P. agardhii rich lake water demonstrated prolonged suppression of cyanobacteria, and displayed a remarkable stability of the newly developed post-HP treatment state of the phytoplankton community. PMID- 26257712 TI - First report of two rapid-onset fatal infections caused by a newly emerging hypervirulent K. Pneumonia ST86 strain of serotype K2 in China. AB - Here, we present the first report of one suspected dead case and two confirmed rapid-onset fatal infections caused by a newly emerging hypervirulent Klebsiella pneumoniae ST86 strain of serotype K2. The three cases occurred in a surgery ward during 2013 in Shanghai, China. A combination of multilocus sequence typing, pulsed-field gel electrophoresis, phenotypic and PCR tests for detecting virulence factors (VFs) was used to identify the isolates as K2 ST86 strains with common VFs, including Aerobactin and rmpA. Furthermore, the two K2 ST86 strains additionally harbored a distinct VF kfu (responsible for iron uptake system), which commonly existed in invasive K1 strains only. Thus, the unusual presence of both K1 and K2 VFs in the lethal ST86 strain might further enhance its hypervirulence and cause rapid onset of a life-threatening infection. Nevertheless, despite the administration of a combined antibiotic treatment, these three patients all died within 24 h of acute onset, thereby highlighting that the importance of early diagnosis to determine whether the ST86 strains harbor key K2 VF and unusual K1 kfu and whether patients should receive a timely and targeted antibiotic therapy to prevent ST86 induced fatal pneumonia. Finally, even though these patients are clinically improved, keeping on with oral antibiotic treatment for additional 2-3 weeks will be also vital for successfully preventing hvKP reinfection or relapse. PMID- 26257711 TI - The universal tree of life: an update. AB - Biologists used to draw schematic "universal" trees of life as metaphors illustrating the history of life. It is indeed a priori possible to construct an organismal tree connecting the three major domains of ribosome encoding organisms: Archaea, Bacteria and Eukarya, since they originated by cell division from LUCA. Several universal trees based on ribosomal RNA sequence comparisons proposed at the end of the last century are still widely used, although some of their main features have been challenged by subsequent analyses. Several authors have proposed to replace the traditional universal tree with a ring of life, whereas others have proposed more recently to include viruses as new domains. These proposals are misleading, suggesting that endosymbiosis can modify the shape of a tree or that viruses originated from the last universal common ancestor (LUCA). I propose here an updated version of Woese's universal tree that includes several rootings for each domain and internal branching within domains that are supported by recent phylogenomic analyses of domain specific proteins. The tree is rooted between Bacteria and Arkarya, a new name proposed for the clade grouping Archaea and Eukarya. A consensus version, in which each of the three domains is unrooted, and a version in which eukaryotes emerged within archaea are also presented. This last scenario assumes the transformation of a modern domain into another, a controversial evolutionary pathway. Viruses are not indicated in these trees but are intrinsically present because they infect the tree from its roots to its leaves. Finally, I present a detailed tree of the domain Archaea, proposing the sub-phylum neo-Euryarchaeota for the monophyletic group of euryarchaeota containing DNA gyrase. These trees, that will be easily updated as new data become available, could be useful to discuss controversial scenarios regarding early life evolution. PMID- 26257713 TI - The Campylobacter jejuni MarR-like transcriptional regulators RrpA and RrpB both influence bacterial responses to oxidative and aerobic stresses. AB - The ability of the human intestinal pathogen Campylobacter jejuni to respond to oxidative stress is central to bacterial survival both in vivo during infection and in the environment. Re-annotation of the C. jejuni NCTC11168 genome revealed the presence of two MarR-type transcriptional regulators Cj1546 and Cj1556, originally annotated as hypothetical proteins, which we have designated RrpA and RrpB (regulator of response to peroxide) respectively. Previously we demonstrated a role for RrpB in both oxidative and aerobic (O2) stress and that RrpB was a DNA binding protein with auto-regulatory activity, typical of MarR-type transcriptional regulators. In this study, we show that RrpA is also a DNA binding protein and that a rrpA mutant in strain 11168H exhibits increased sensitivity to hydrogen peroxide oxidative stress. Mutation of either rrpA or rrpB reduces catalase (KatA) expression. However, a rrpAB double mutant exhibits higher levels of resistance to hydrogen peroxide oxidative stress, with levels of KatA expression similar to the wild-type strain. Mutation of either rrpA or rrpB also results in a reduction in the level of katA expression, but this reduction was not observed in the rrpAB double mutant. Neither the rrpA nor rrpB mutant exhibits any significant difference in sensitivity to either cumene hydroperoxide or menadione oxidative stresses, but both mutants exhibit a reduced ability to survive aerobic (O2) stress, enhanced biofilm formation and reduced virulence in the Galleria mellonella infection model. The rrpAB double mutant exhibits wild type levels of biofilm formation and wild-type levels of virulence in the G mellonella infection model. Together these data indicate a role for both RrpA and RrpB in the C. jejuni peroxide oxidative and aerobic (O2) stress responses, enhancing bacterial survival in vivo and in the environment. PMID- 26257714 TI - Microsensor measurements of hydrogen gas dynamics in cyanobacterial microbial mats. AB - We used a novel amperometric microsensor for measuring hydrogen gas production and consumption at high spatio-temporal resolution in cyanobacterial biofilms and mats dominated by non-heterocystous filamentous cyanobacteria (Microcoleus chtonoplastes and Oscillatoria sp.). The new microsensor is based on the use of an organic electrolyte and a stable internal reference system and can be equipped with a chemical sulfide trap in the measuring tip; it exhibits very stable and sulfide-insensitive measuring signals and a high sensitivity (1.5-5 pA per MUmol L(-1) H2). Hydrogen gas measurements were done in combination with microsensor measurements of scalar irradiance, O2, pH, and H2S and showed a pronounced H2 accumulation (of up to 8-10% H2 saturation) within the upper mm of cyanobacterial mats after onset of darkness and O2 depletion. The peak concentration of H2 increased with the irradiance level prior to darkening. After an initial build-up over the first 1-2 h in darkness, H2 was depleted over several hours due to efflux to the overlaying water, and due to biogeochemical processes in the uppermost oxic layers and the anoxic layers of the mats. Depletion could be prevented by addition of molybdate pointing to sulfate reduction as a major sink for H2. Immediately after onset of illumination, a short burst of presumably photo-produced H2 due to direct biophotolysis was observed in the illuminated but anoxic mat layers. As soon as O2 from photosynthesis started to accumulate, the H2 was consumed rapidly and production ceased. Our data give detailed insights into the microscale distribution and dynamics of H2 in cyanobacterial biofilms and mats, and further support that cyanobacterial H2 production can play a significant role in fueling anaerobic processes like e.g., sulfate reduction or anoxygenic photosynthesis in microbial mats. PMID- 26257715 TI - Bacterial diversity differences along an epigenic cave stream reveal evidence of community dynamics, succession, and stability. AB - Unchanging physicochemical conditions and nutrient sources over long periods of time in cave and karst subsurface habitats, particularly aquifers, can support stable ecosystems, termed autochthonous microbial endokarst communities (AMEC). AMEC existence is unknown for other karst settings, such as epigenic cave streams. Conceptually, AMEC should not form in streams due to faster turnover rates and seasonal disturbances that have the capacity to transport large quantities of water and sediment and to change allochthonous nutrient and organic matter sources. Our goal was to investigate whether AMEC could form and persist in hydrologically active, epigenic cave streams. We analyzed bacterial diversity from cave water, sediments, and artificial substrates (Bio-Traps(r)) placed in the cave at upstream and downstream locations. Distinct communities existed for the water, sediments, and Bio-Trap(r) samplers. Throughout the study period, a subset of community members persisted in the water, regardless of hydrological disturbances. Stable habitat conditions based on flow regimes resulted in more than one contemporaneous, stable community throughout the epigenic cave stream. However, evidence for AMEC was insufficient for the cave water or sediments. Community succession, specifically as predictable exogenous heterotrophic microbial community succession, was evident from decreases in community richness from the Bio-Traps(r), a peak in Bio-Trap(r) community biomass, and from changes in the composition of Bio-Trap(r) communities. The planktonic community was compositionally similar to Bio-Trap(r) initial colonizers, but the downstream Bio Trap(r) community became more similar to the sediment community at the same location. These results can help in understanding the diversity of planktonic and attached microbial communities from karst, as well as microbial community dynamics, stability, and succession during disturbance or contamination responses over time. PMID- 26257716 TI - Reconstruction of the temporal signaling network in Salmonella-infected human cells. AB - Salmonella enterica is a bacterial pathogen that usually infects its host through food sources. Translocation of the pathogen proteins into the host cells leads to changes in the signaling mechanism either by activating or inhibiting the host proteins. Given that the bacterial infection modifies the response network of the host, a more coherent view of the underlying biological processes and the signaling networks can be obtained by using a network modeling approach based on the reverse engineering principles. In this work, we have used a published temporal phosphoproteomic dataset of Salmonella-infected human cells and reconstructed the temporal signaling network of the human host by integrating the interactome and the phosphoproteomic dataset. We have combined two well established network modeling frameworks, the Prize-collecting Steiner Forest (PCSF) approach and the Integer Linear Programming (ILP) based edge inference approach. The resulting network conserves the information on temporality, direction of interactions, while revealing hidden entities in the signaling, such as the SNARE binding, mTOR signaling, immune response, cytoskeleton organization, and apoptosis pathways. Targets of the Salmonella effectors in the host cells such as CDC42, RHOA, 14-3-3delta, Syntaxin family, Oxysterol-binding proteins were included in the reconstructed signaling network although they were not present in the initial phosphoproteomic data. We believe that integrated approaches, such as the one presented here, have a high potential for the identification of clinical targets in infectious diseases, especially in the Salmonella infections. PMID- 26257717 TI - Efficacy of a coating composed of chitosan from Mucor circinelloides and carvacrol to control Aspergillus flavus and the quality of cherry tomato fruits. AB - Cherry tomato (Lycopersicon esculentum Mill) fruits are susceptible to contamination by Aspergillus flavus, which may cause the development of fruit rot and significant postharvest losses. Currently there are significant drawbacks for the use of synthetic fungicides to control pathogenic fungi in tomato fruits, and it has increased the interest in exploring new alternatives to control the occurrence of fungal infections in these fruits. This study evaluated the efficacy of chitosan (CHI) from Mucor circinelloides in combination with carvacrol (CAR) in inhibiting A. flavus in laboratory media and as a coating on cherry tomato fruits (25 degrees C, 12 days and 12 degrees C, 24 days). During a period of storage, the effect of coatings composed of CHI and CAR on autochthonous microflora, as well as on some quality characteristics of the fruits such as weight loss, color, firmness, soluble solids, and titratable acidity was evaluated. CHI and CAR displayed MIC valuesof 7.5 mg/mL and 10 MUL/mL, respectively, against A. flavus. The combined application of CHI (7.5 or 3.75 mg/mL) and CAR (5 or 2.5 MUL/mL) strongly inhibited the mycelial growth and spore germination of A. flavus. The coating composed of CHI (3.75 mg/mL) and CAR (2.5 or 1.25 MUL/mL) inhibited the growth of A. flavus in artificially contaminated fruits, as well as the native fungal microflora of the fruits stored at room or low temperature. The application of the tested coatings preserved the quality of cherry tomato fruits as measured by some physicochemical attributes. From this, composite coatings containing CHI and CAR offer a promising alternative to control postharvest infection caused by A. flavus or native fungal microflora in fresh cherry tomato fruits without negatively affecting their quality over storage. PMID- 26257718 TI - Drivers of the dynamics of diazotrophs and denitrifiers in North Sea bottom waters and sediments. AB - The fixation of dinitrogen (N2) and denitrification are two opposite processes in the nitrogen cycle. The former transfers atmospheric dinitrogen gas into bound nitrogen in the biosphere, while the latter returns this bound nitrogen back to atmospheric dinitrogen. It is unclear whether or not these processes are intimately connected in any microbial ecosystem or that they are spatially and/or temporally separated. Here, we measured seafloor nitrogen fixation and denitrification as well as pelagic nitrogen fixation by using the stable isotope technique. Alongside, we measured the diversity, abundance, and activity of nitrogen-fixing and denitrifying microorganisms at three stations in the southern North Sea. Nitrogen fixation ranged from undetectable to 2.4 nmol N L(-1) d(-1) and from undetectable to 8.2 nmol N g(-1) d(-1) in the water column and seafloor, respectively. The highest rates were measured in August at Doggersbank, both for the water column and for the seafloor. Denitrification ranged from 1.7 to 208.8 MUmol m(-2) d(-1) and the highest rates were measured in May at the Oyster Grounds. DNA sequence analysis showed sequences of nifH, a structural gene for nitrogenase, related to sequences from anaerobic sulfur/iron reducers and sulfate reducers. Sequences of the structural gene for nitrite reductase, nirS, were related to environmental clones from marine sediments. Quantitative polymerase chain reaction (qPCR) data revealed the highest abundance of nifH and nirS genes at the Oyster Grounds. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) data revealed the highest nifH expression at Doggersbank and the highest nirS expression at the Oyster Grounds. The distribution of the diazotrophic and denitrifying communities seems to be subject to different selecting factors, leading to spatial and temporal separation of nitrogen fixation and denitrification. These selecting factors include temperature, organic matter availability, and oxygen concentration. PMID- 26257719 TI - Exploring the role of sigma factor gene expression on production by Corynebacterium glutamicum: sigma factor H and FMN as example. AB - Bacteria are known to cope with environmental changes by using alternative sigma factors binding to RNA polymerase core enzyme. Sigma factor is one of the targets to modify transcription regulation in bacteria and to influence production capacities. In this study, the effect of overexpressing each annotated sigma factor gene in Corynebacterium glutamicum WT was assayed using an IPTG inducible plasmid system and different IPTG concentrations. It was revealed that growth was severely decreased when sigD or sigH were overexpressed with IPTG concentrations higher than 50 MUM. Overexpression of sigH led to an obvious phenotypic change, a yellow-colored supernatant. High performance liquid chromatography analysis revealed that riboflavin was excreted to the medium when sigH was overexpressed and DNA microarray analysis confirmed increased expression of riboflavin biosynthesis genes. In addition, genes for enzymes related to the pentose phosphate pathway and for enzymes dependent on flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), or NADPH as cofactor were upregulated when sigH was overexpressed. To test if sigH overexpression can be exploited for production of riboflavin-derived FMN or FAD, the endogenous gene for bifunctional riboflavin kinase/FMN adenyltransferase was co-expressed with sigH from a plasmid. Balanced expression of sigH and ribF improved accumulation of riboflavin (19.8 +/- 0.3 MUM) and allowed for its conversion to FMN (33.1 +/- 1.8 MUM) in the supernatant. While a proof-of-concept was reached, conversion was not complete and titers were not high. This study revealed that inducible and gradable overexpression of sigma factor genes is an interesting approach to switch gene expression profiles and to discover untapped potential of bacteria for chemical production. PMID- 26257720 TI - Diversity of multi-drug resistant Acinetobacter baumannii population in a major hospital in Kuwait. AB - Acinetobacter baumannii is one of the most important opportunistic pathogens that causes serious health care associated complications in critically ill patients. In the current study we report on the diversity of the clinical multi-drug resistant (MDR) A. baumannii in Kuwait by molecular characterization. One hundred A. baumannii were isolated from one of the largest governmental hospitals in Kuwait. Following the identification of the isolates by molecular methods, the amplified bla OXA-51-like gene product of one isolate (KO-12) recovered from blood showed the insertion of the ISAba19 at position 379 in bla OXA-78. Of the 33 MDR isolates, 28 (85%) contained bla OXA-23, 2 (6%) bla OXA-24 and 6 (18%) bla PER-1 gene. We did not detect bla OXA-58, bla VIM, bla IMP, bla GES, bla VEB, and bla NDM genes in any of the tested isolates. In three bla PER-1 positive isolates the genetic environment of bla PER-1 consisted of two copies of ISPa12 (tnpiA1) surrounding the bla PER-1 gene on a highly stable plasmid of ca. 140-kb. Multilocus-sequence typing (MLST) analysis of the 33 A. baumannii isolates identified 20 different STs, of which six (ST-607, ST-608, ST-609, ST-610, ST 611, and ST-612) were novel. Emerging STs such as ST15 (identified for the first time in the Middle East), ST78 and ST25 were also detected. The predominant clonal complex was CC2. Pulsed-field gel electrophoresis and MLST defined the MDR isolates as multi-clonal with diverse lineages. Our results lead us to believe that A. baumannii is diverse in clonal origins and/or is undergoing clonal expansion continuously while multiple lineages of MDR A. baumannii circulate in hospital ward simultaneously. PMID- 26257721 TI - Plant growth promotion induced by phosphate solubilizing endophytic Pseudomonas isolates. AB - The use of plant growth promoting bacterial inoculants as live microbial biofertilizers provides a promising alternative to chemical fertilizers and pesticides. Inorganic phosphate solubilization is one of the major mechanisms of plant growth promotion by plant associated bacteria. This involves bacteria releasing organic acids into the soil which solubilize the phosphate complexes converting them into ortho-phosphate which is available for plant up-take and utilization. The study presented here describes the ability of endophytic bacteria to produce gluconic acid (GA), solubilize insoluble phosphate, and stimulate the growth of Pisum sativum L. plants. This study also describes the genetic systems within three of these endophyte strains thought to be responsible for their effective phosphate solubilizing abilities. The results showed that many of the endophytic strains produced GA (14-169 mM) and have moderate to high phosphate solubilization capacities (~400-1300 mg L(-1)). When inoculated into P. sativum L. plants grown in soil under soluble phosphate limiting conditions, the endophytes that produced medium-high levels of GA displayed beneficial plant growth promotion effects. PMID- 26257722 TI - Co(2+)-dependent gene expression in Streptococcus pneumoniae: opposite effect of Mn(2+) and Co(2+) on the expression of the virulence genes psaBCA, pcpA, and prtA. AB - Manganese (Mn(2+))-, zinc (Zn(2+))- and copper (Cu(2+)) play significant roles in transcriptional gene regulation, physiology, and virulence of Streptococcus pneumoniae. So far, the effect of the important transition metal ion cobalt (Co(2+)) on gene expression of S. pneumoniae has not yet been explored. Here, we study the impact of Co(2+) stress on the transcriptome of S. pneumoniae strain D39. BLAST searches revealed that the genome of S. pneumoniae encodes a putative Co(2+)-transport operon (cbi operon), the expression of which we show here to be induced by a high Co(2+) concentration. Furthermore, we found that Co(2+), as has been shown previously for Zn(2+), can cause derepression of the genes of the PsaR virulence regulon, encoding the Mn(2+)-uptake system PsaBCA, the choline binding protein PcpA and the cell-wall associated serine protease PrtA. Interestingly, although Mn(2+) represses expression of the PsaR regulon and Co(2+) leads to derepression, both metal ions stimulate interaction of PsaR with its target promoters. These data will be discussed in the light of previous studies on similar metal-responsive transcriptional regulators. PMID- 26257723 TI - Giardia fatty acyl-CoA synthetases as potential drug targets. AB - Giardiasis caused by Giardia intestinalis (syn. G. lamblia, G. duodenalis) is one of the leading causes of diarrheal parasitic diseases worldwide. Although limited drugs to treat giardiasis are available, there are concerns regarding toxicity in some patients and the emerging drug resistance. By data-mining genome sequences, we observed that G. intestinalis is incapable of synthesizing fatty acids (FA) de novo. However, this parasite has five long-chain fatty acyl-CoA synthetases (GiACS1 to GiACS5) to activate FA scavenged from the host. ACS is an essential enzyme because FA need to be activated to form acyl-CoA thioesters before they can enter subsequent metabolism. In the present study, we performed experiments to explore whether some GiACS enzymes could serve as drug targets in Giardia. Based on the high-throughput datasets and protein modeling analyses, we initially studied the GiACS1 and GiACS2, because genes encoding these two enzymes were found to be more consistently expressed in varied parasite life cycle stages and when interacting with host cells based on previously reported transcriptome data. These two proteins were cloned and expressed as recombinant proteins. Biochemical analysis revealed that both had apparent substrate preference toward palmitic acid (C16:0) and myristic acid (C14:0), and allosteric or Michaelis-Menten kinetics on palmitic acid or ATP. The ACS inhibitor triacsin C inhibited the activity of both enzymes (IC50 = 1.56 MUM, K i = 0.18 MUM for GiACS1, and IC50 = 2.28 MUM, K i = 0.23 MUM for GiACS2, respectively) and the growth of G. intestinalis in vitro (IC50 = 0.8 MUM). As expected from giardial evolutionary characteristics, both GiACSs displayed differences in overall folding structure as compared with their human counterparts. These observations support the notion that some of the GiACS enzymes may be explored as drug targets in this parasite. PMID- 26257724 TI - New multiplex PCR methods for rapid screening of genetically modified organisms in foods. AB - We present novel multiplex PCR methods for rapid and reliable screening of genetically modified organisms (GMOs). New designed PCR primers targeting four frequently used GMO specific sequences permitted identification of new DNA markers, in particular 141 bp fragment of cauliflower mosaic virus (CaMV) 35S promoter, 224 bp fragment of Agrobacterium tumefaciens nopaline synthase (NOS) terminator, 256 bp fragment of 5-enolppyruvylshikimate-phosphate synthase (epsps) gene and 258 bp fragment of Cry1Ab delta-endotoxin (cry1Ab) gene for GMO screening. The certified reference materials containing Roundup Ready soybean (RRS) and maize MON 810 were applied for the development and optimization of uniplex and multiplex PCR systems. Evaluation of amplification products by agarose gel electrophoresis using negative and positive controls confirmed high specificity and sensitivity at 0.1% GMO for both RRS and MON 810. The fourplex PCR was developed and optimized that allows simultaneous detection of three common transgenic elements, such as: CaMV 35S promoter, NOS terminator, epsps gene together with soybean-specific lectin gene. The triplex PCR developed enables simultaneous identification of transgenic elements, such as: 35S promoter and cry1Ab gene together with maize zein gene. The analysis of different processed foods demonstrated that multiplex PCR methods developed in this study are useful for accurate and fast screening of GM food products. PMID- 26257725 TI - Vesicles-mediated resistance to antibiotics in bacteria. PMID- 26257726 TI - In vivo antimicrobial activity of marbofloxacin against Pasteurella multocida in a tissue cage model in calves. AB - Marbofloxacin is a fluoroquinolone specially developed for use in veterinary medicine with broad-spectrum antibacterial activity. The objective of our study was to re-evaluate in vivo antimicrobial activity of marbofloxacin against Pasteurella multocida using subcutaneously implanted tissue cages in calves. Calves were infected by direct injection into tissue cages with P. multocida(type B, serotype 2), then intramuscularly received a range of marbofloxacin doses 24 h after inoculation. The ratio of 24 h area under the concentration-time curve divided by the minimum inhibitory concentration or the mutant prevention concentration (AUC24 h/MIC or AUC24 h/MPC) was the pharmacokinetic pharmacodynamic (PK/PD) index that best described the effectiveness of marbofloxacin against P. multocida (R (2) = 0.8514) by non-linear regression analysis. Marbofloxacin exhibited a good antimicrobial activity in vivo. The levels of AUC24 h/MIC and AUC24 h/MPC that produced 50% (1.5log10 CFU/mL reduction) and 90% (3log10 CFU/mL reduction) of maximum response were 18.60 and 50.65 h, 4.67 and 12.89 h by using sigmoid Emax model WINNONLIN software, respectively. The in vivo PK/PD integrated methods by tissue cage model display the advantage of the evaluation of antimicrobial activity and the optimization of the dosage regimen for antibiotics in the presence of the host defenses, especially in target animal of veterinary interest. PMID- 26257727 TI - Molecular evidence of a Trypanosoma brucei gambiense sylvatic cycle in the human african trypanosomiasis foci of Equatorial Guinea. AB - Gambiense trypanosomiasis is considered an anthroponotic disease. Consequently, control programs are generally aimed at stopping transmission of Trypanosoma brucei gambiense (T. b. gambiense) by detecting and treating human cases. However, the persistence of numerous foci despite efforts to eliminate this disease questions this strategy as unique tool to pursue the eradication. The role of animals as a reservoir of T. b. gambiense is still controversial, but could partly explain maintenance of the infection at hypo-endemic levels. In the present study, we evaluated the presence of T. b. gambiense in wild animals in Equatorial Guinea. The infection rate ranged from 0.8% in the insular focus of Luba to more than 12% in Mbini, a focus with a constant trickle of human cases. The parasite was detected in a wide range of animal species including four species never described previously as putative reservoirs. Our study comes to reinforce the hypothesis that animals may play a role in the persistence of T. b. gambiense transmission, being particularly relevant in low transmission settings. Under these conditions the integration of sustained vector control and medical interventions should be considered to achieve the elimination of gambiense trypanosomiasis. PMID- 26257728 TI - Development of Paramyosin as a Vaccine Candidate for Schistosomiasis. AB - Schistosomiasis, caused by three principal species of diecious trematodes (flatworms), currently afflicts over 250 million individuals, results in an estimated 2-15% chronic disability, and contributes to poor health and economic stagnation in endemic areas. Although schistosomiasis is effectively treated with praziquantel, rapid reinfection with rebound morbidity precludes effective control based on chemotherapy alone and justifies current efforts to develop vaccines for these parasites. Paramyosin (Pmy), an invertebrate muscle-associated protein, has emerged as a promising vaccine candidate for both Schistosoma mansoni and Schistosoma japonicum. Herein, we discuss the discovery of Pmy, its development as a vaccine candidate in rodents and bovines, as well as studies of naturally occurring immune responses to Pmy in prospective, observational human studies. We conclude with a proposed developmental plan to move Pmy toward Phase I clinical trials. PMID- 26257729 TI - IL-15-PI3K-AKT-mTOR: A Critical Pathway in the Life Journey of Natural Killer Cells. AB - Among numerous cytokines modulating natural killer (NK) cell function, interleukin 15 (IL-15) exerts a broad range of effect from development and homeostasis, to activation of mature NK cells during infection. Its significance is further highlighted by clinical trials in which IL-15 is being used to boost the proliferation and anti-tumor response of NK cells. Among the signal transduction pathways triggered by the engagement of IL-15 receptor with its ligand, the PI3K-AKT-mTOR pathway seems to be critical for the IL-15-mediated activation of NK cells, therefore being responsible for efficient anti-viral and anti-tumor responses. This review provides an overview of the role of IL-15 at multiple stages of NK cell life journey. Understanding the pathway by which IL-15 conveys critical signals for the generation of NK cells with efficient effector functions, in combination with established protocols for NK cell expansion ex vivo, will undoubtedly open new avenues for therapeutic applications for immunomodulation against infections and cancers. PMID- 26257730 TI - Overexpression of Bovine FcRn in Mice Enhances T-Dependent Immune Responses by Amplifying T Helper Cell Frequency and Germinal Center Enlargement in the Spleen. AB - The neonatal Fc receptor (FcRn) plays key roles in IgG and albumin homeostasis, maternal IgG transport, and antigen presentation of IgG-opsonized antigens. Previously, we reported that transgenic (Tg) mice that overexpress the bovine FcRn (bFcRn) have augmented T-dependent humoral immune response with increased IgG protection, higher level of antigen-specific antibodies, greater number of antigen-specific B cells, and effective immune response even against weakly immunogenic epitopes. In the current study, we analyzed the localization of the bFcRn in secondary lymphoid organs, and focused to demonstrate the in vivo impact of its overexpression in the spleen on the course of antibody production. bFcRn was highly expressed by red pulp macrophages and marginal zone macrophages in the spleen and by subcapsular sinus macrophages and macrophage-like cells in the interfollicular areas in the lymph node cortex. We also demonstrated that splenic dendritic cells of Tg mice express bFcRn and intraperitoneal immunization of these mice with T-dependent antigens led to more than threefold increase in the number of antigen-specific activated T helper cells with increased size and numbers of germinal centers compared to wild-type controls. bFcRn expression in splenic B cells was also detected and that may also contribute to the enhanced B cell activation. Finally, we demonstrated that these Tg mice developed efficient immune response against very low dose of antigen, reflecting another important practical benefit of these Tg mice. PMID- 26257731 TI - Modulating the Innate Immune Response to Influenza A Virus: Potential Therapeutic Use of Anti-Inflammatory Drugs. AB - Infection by influenza A viruses (IAV) is frequently characterized by robust inflammation that is usually more pronounced in the case of avian influenza. It is becoming clearer that the morbidity and pathogenesis caused by IAV are consequences of this inflammatory response, with several components of the innate immune system acting as the main players. It has been postulated that using a therapeutic approach to limit the innate immune response in combination with antiviral drugs has the potential to diminish symptoms and tissue damage caused by IAV infection. Indeed, some anti-inflammatory agents have been shown to be effective in animal models in reducing IAV pathology as a proof of principle. The main challenge in developing such therapies is to selectively modulate signaling pathways that contribute to lung injury while maintaining the ability of the host cells to mount an antiviral response to control virus replication. However, the dissection of those pathways is very complex given the numerous components regulated by the same factors (i.e., NF kappa B transcription factors) and the large number of players involved in this regulation, some of which may be undescribed or unknown. This article provides a comprehensive review of the current knowledge regarding the innate immune responses associated with tissue damage by IAV infection, the understanding of which is essential for the development of effective immunomodulatory drugs. Furthermore, we summarize the recent advances on the development and evaluation of such drugs as well as the lessons learned from those studies. PMID- 26257732 TI - Role of Tumor Necrosis Factor Superfamily in Neuroinflammation and Autoimmunity. AB - Tumor necrosis factor superfamily (TNFSF) molecules play an important role in the activation, proliferation, differentiation, and migration of immune cells into the central nervous system (CNS). Several TNF superfamily molecules are known to control alloimmunity, autoimmunity, and immunity. Development of transgenic and gene knockout animals, and monoclonal antibodies against TNFSF molecules have increased our understanding of individual receptor-ligand interactions, and their intracellular signaling during homeostasis and neuroinflammation. A strong clinical association has been observed between TNFSF members and CNS autoimmunity such as multiple sclerosis and also in its animal model experimental autoimmune encephalomyelitis. Therefore, they are promising targets for alternative therapeutic options to control autoimmunity. Although, TNFSF ligands are widely distributed and have diverse functions, we have restricted the discussions in this review to TNFSF receptor-ligand interactions and their role in the pathogenesis of neuroinflammation and CNS autoimmunity. PMID- 26257733 TI - Thymic Crosstalk Coordinates Medulla Organization and T-Cell Tolerance Induction. AB - The thymus ensures the generation of a functional and highly diverse T-cell repertoire. The thymic medulla, which is mainly composed of medullary thymic epithelial cells (mTECs) and dendritic cells (DCs), provides a specialized microenvironment dedicated to the establishment of T-cell tolerance. mTECs play a privileged role in this pivotal process by their unique capacity to express a broad range of peripheral self-antigens that are presented to developing T cells. Reciprocally, developing T cells control mTEC differentiation and organization. These bidirectional interactions are commonly referred to as thymic crosstalk. This review focuses on the relative contributions of mTEC and DC subsets to the deletion of autoreactive T cells and the generation of natural regulatory T cells. We also summarize current knowledge regarding how hematopoietic cells conversely control the composition and complex three-dimensional organization of the thymic medulla. PMID- 26257734 TI - Exosomes in the Thymus: Antigen Transfer and Vesicles. AB - Thymocytes go through several steps of maturation and selection in the thymus in order to form a functional pool of effector T-cells and regulatory T-cells in the periphery. Close interactions between thymocytes, thymic epithelial cells, and dendritic cells are of vital importance for the maturation, selection, and lineage decision of the thymocytes. One important question that is still unanswered is how a relatively small epithelial cell population can present a vast array of self-antigens to the manifold larger population of developing thymocytes in this selection process. Here, we review and discuss the literature concerning antigen transfer from epithelial cells with a focus on exosomes. Exosomes are nano-sized vesicles released from a cell into the extracellular space. These vesicles can carry proteins, microRNAs, and mRNAs between cells and are thus able to participate in intercellular communication. Exosomes have been shown to be produced by thymic epithelial cells and to carry tissue-restricted antigens and MHC molecules, which may enable them to participate in the thymocyte selection process. PMID- 26257735 TI - Polarizing T and B Cell Responses by APC-Targeted Subunit Vaccines. AB - Current influenza vaccines mostly aim at the induction of specific neutralizing antibodies. While antibodies are important for protection against a particular virus strain, T cells can recognize epitopes that will offer broader protection against influenza. We have previously developed a DNA vaccine format by which protein antigens can be targeted specifically to receptors on antigen presenting cells (APCs). The DNA-encoded vaccine proteins are homodimers, each chain consisting of a targeting unit, a dimerization unit, and an antigen. The strategy of targeting antigen to APCs greatly enhances immune responses as compared to non targeted controls. Furthermore, targeting of antigen to different receptors on APCs can polarize the immune response to different arms of immunity. Here, we discuss how targeting of hemagglutinin to MHC class II molecules increases Th2 and IgG1 antibody responses, whereas targeting to chemokine receptors XCR1 or CCR1/3/5 increases Th1 and IgG2a responses, in addition to CD8(+) T cell responses. We also discuss these results in relation to work published by others on APC-targeting. Differential targeting of APC surface molecules may allow the induction of tailor-made phenotypes of adaptive immune responses that are optimal for protection against various infectious agents, including influenza virus. PMID- 26257736 TI - Tasting Pseudomonas aeruginosa Biofilms: Human Neutrophils Express the Bitter Receptor T2R38 as Sensor for the Quorum Sensing Molecule N-(3-Oxododecanoyl)-l Homoserine Lactone. AB - Bacteria communicate with one another via specialized signaling molecules, known as quorum sensing molecules or autoinducers. The Pseudomonas aeruginosa-derived quorum sensing molecule N-(3-oxododecanoyl)-l-homoserine lactone (AHL-12), however, also activates mammalian cells. As shown previously, AHL-12-induced chemotaxis, up-regulated CD11b expression, and enhanced phagocytosis of polymorphonuclear neutrophils. Circumstantial evidence concurred with a receptor for AHL-12, which has been elusive so far. We now investigated the bitter receptor T2R38 as a potential candidate. Although identified as a taste receptor, extragustatory cells express T2R38, for example, epithelial cells in the lung. We now detected T2R38 in peripheral blood neutrophils, monocytes, and lymphocytes. T2R38 is not only found on the cell membrane but also intracellular. In neutrophils, T2R38 was located in vesicles with characteristics of lipid droplets, and super-resolution microscopy showed a co-localization with the lipid droplet membrane. Neutrophils take up AHL-12, and it co-localized with T2R38 as seen by laser scan microscopy. Binding of AHL-12 to T2R28 was confirmed by pull down assays using biotin-coupled AHL-12 as bait. A commercially available antibody to T2R38 inhibited binding of AHL-12 to neutrophils, and this antibody by itself stimulated neutrophils, similarly to AHL-12. In conclusion, our data provide evidence for expression of functional T2R38 on neutrophils, and are compatible with the notion that T2R38 is the receptor for AHL-12. PMID- 26257737 TI - The Many Alternative Faces of Macrophage Activation. AB - Monocytes and macrophages provide the first line of defense against pathogens. They also initiate acquired immunity by processing and presenting antigens and provide the downstream effector functions. Analysis of large gene expression datasets from multiple cells and tissues reveals sets of genes that are co regulated with the transcription factors that regulate them. In macrophages, the gene clusters include lineage-specific genes, interferon-responsive genes, early inflammatory genes, and genes required for endocytosis and lysosome function. Macrophages enter tissues and alter their function to deal with a wide range of challenges related to development and organogenesis, tissue injury, malignancy, sterile, or pathogenic inflammatory stimuli. These stimuli alter the gene expression to produce "activated macrophages" that are better equipped to eliminate the cause of their influx and to restore homeostasis. Activation or polarization states of macrophages have been classified as "classical" and "alternative" or M1 and M2. These proposed states of cells are not supported by large-scale transcriptomic data, including macrophage-associated signatures from large cancer tissue datasets, where the supposed markers do not correlate with other. Individual macrophage cells differ markedly from each other, and change their functions in response to doses and combinations of agonists and time. The most studied macrophage activation response is the transcriptional cascade initiated by the TLR4 agonist lipopolysaccharide. This response is reviewed herein. The network topology is conserved across species, but genes within the transcriptional network evolve rapidly and differ between mouse and human. There is also considerable divergence in the sets of target genes between mouse strains, between individuals, and in other species such as pigs. The deluge of complex information related to macrophage activation can be accessed with new analytical tools and new databases that provide access for the non-expert. PMID- 26257738 TI - Editorial: "Recent Advances in Gamma/Delta T Cell Biology: New Ligands, New Functions, and New Translational Perspectives". PMID- 26257739 TI - MHC Class II Auto-Antigen Presentation is Unconventional. AB - Antigen presentation is highly critical in adoptive immunity. Only by interacting with antigens presented by major histocompatibility complex class II molecules, helper T cells can be stimulated to fight infections or diseases. The degradation of a full protein into small peptide fragments bound to class II molecules is a dynamic, lengthy process consisting of many steps and chaperons. Deregulation in any step of antigen processing could lead to the development of self-reactive T cells or defective immune response to pathogens. Indeed, human leukocyte antigens class II genes are the predominant contributors to susceptibility to autoimmune diseases. Conventional antigen-processing calls for internalization of extracellular antigens followed by processing and epitope selection within antigen-processing subcellular compartments, enriched with all necessary accessory molecules, processing enzymes, and proper pH and denaturing conditions. However, recent data examining the temporal relationship between antigen uptakes, processing, and epitope selection revealed unexpected characteristics for auto antigenic epitopes, which were not shared with antigenic epitopes from pathogens. This review provides a discussion of the relevance of these findings to the mechanisms of autoimmunity. PMID- 26257741 TI - Signature Channels of Excitability no More: L-Type Channels in Immune Cells. AB - Although the concept of Ca(2+) as a universal messenger is well established, it was assumed that the regulatory mechanisms of Ca(2+)-signaling were divided along the line of electric excitability. Recent advances in molecular biology and genomics have, however, provided evidence that non-excitable cells such as immunocytes also express a wide and diverse pool of ion channels that does not differ as significantly from that of excitable cells as originally assumed. Ion channels and transporters are involved in virtually all aspects of immune response regulation, from cell differentiation and development to activation, and effector functions such as migration, antibody-secretion, phagosomal maturation, or vesicular delivery of bactericidal agents. This comprises TRP channel family members, voltage- and Ca(2+)-gated K(+)- and Na(+)-channels, as well as unexpectedly, components of the CaV1-subfamily of voltage-gated L-type Ca(2+) channels, originally thought to be signature molecules of excitability. This article provides an overview of recent observations made in the field of CaV1 L type channel function in the immune context, as well as presents results we obtained studying these channels in B-lymphocytes. PMID- 26257742 TI - Thymic B Cells and Central T Cell Tolerance. AB - Central T cell tolerance is believed to be mainly induced by thymic dendritic cells and medullary thymic epithelial cells. The thymus also harbors substantial numbers of B cells. These may arise though intrathymic B lymphopoiesis or immigration from the bloodstream. Importantly, and in contrast to resting "mainstream" B cells in the periphery, thymic B cells display elevated levels of MHC class II and constitutively express CD80. Arguably, their most unexpected feature is the expression of autoimmune regulator. These unique features of thymic B cells result from a licensing process that involves cross-talk with CD4 single-positive T cells and CD40 signaling. Together, these recent findings suggest that B cells play a more prominent role as thymic APCs than previously appreciated. PMID- 26257740 TI - MIF and CXCL12 in Cardiovascular Diseases: Functional Differences and Similarities. AB - Coronary artery disease (CAD) as part of the cardiovascular diseases is a pathology caused by atherosclerosis, a chronic inflammatory disease of the vessel wall characterized by a massive invasion of lipids and inflammatory cells into the inner vessel layer (intima) leading to the formation of atherosclerotic lesions; their constant growth may cause complications such as flow-limiting stenosis and plaque rupture, the latter triggering vessel occlusion through thrombus formation. Pathophysiology of CAD is complex and over the last years many players have entered the picture. One of the latter being chemokines (small 8-12 kDa cytokines) and their receptors, known to orchestrate cell chemotaxis and arrest. Here, we will focus on the chemokine CXCL12, also known as stromal cell derived factor 1 (SDF-1) and the chemokine-like function chemokine, macrophage migration-inhibitory factor (MIF). Both are ubiquitously expressed and highly conserved proteins and play an important role in cell homeostasis, recruitment, and arrest through binding to their corresponding chemokine receptors CXCR4 (CXCL12 and MIF), ACKR3 (CXCL12), and CXCR2 (MIF). In addition, MIF also binds to the receptor CD44 and the co-receptor CD74. CXCL12 has mostly been studied for its crucial role in the homing of (hematopoietic) progenitor cells in the bone marrow and their mobilization into the periphery. In contrast to CXCL12, MIF is secreted in response to diverse inflammatory stimuli, and has been associated with a clear pro-inflammatory and pro-atherogenic role in multiple studies of patients and animal models. Ongoing research on CXCL12 points at a protective function of this chemokine in atherosclerotic lesion development. This review will focus on the role of CXCL12 and MIF and their differences and similarities in CAD of high risk patients. PMID- 26257743 TI - Enhancing Human Immunodeficiency Virus-Specific CD8(+) T Cell Responses with Heteroclitic Peptides. AB - Human immunodeficiency virus (HIV)-specific CD8(+) T cells play a critical role in containing HIV replication and delaying disease progression. However, HIV specific CD8(+) T cells become progressively more "exhausted" as chronic HIV infection proceeds. Symptoms of T cell exhaustion range from expression of inhibitory receptors and selective loss of cytokine production capacity through reduced proliferative potential, impaired differentiation into effector cells and increased susceptibility to apoptosis. While effective combination antiretroviral therapy (cART) durably reduces HIV viremia to undetectable levels, this alone does not restore the full pluripotency of HIV-specific CD8(+) T cells. In a number of studies, a subset of peptide epitope variants categorized as heteroclitic, restimulated more potent cellular immune responses in vitro than did the native, immunizing peptides themselves. This property of heteroclitic peptides has been exploited in experimental cancer and chronic viral infection models to promote clearance of transformed cells and persistent viruses. In this review, we consider the possibility that heteroclitic peptides could improve the efficacy of therapeutic vaccines as part of HIV immunotherapy or eradication strategies. We review literature on heteroclitic peptides and illustrate their potential to beneficially modulate the nature of HIV-specific T cell responses toward those found in the small minority of HIV-infected, aviremic cART-naive persons termed elite controllers or long-term non-progressors. Our review suggests that the efficacy of HIV vaccines could be improved by identification, testing, and incorporation of heteroclitic variants of native HIV peptide epitopes. PMID- 26257745 TI - Editorial: Novel Clinical Applications of Extracellular Vesicles. PMID- 26257744 TI - iNKT Cells and Their Potential Lipid Ligands during Viral Infection. AB - Invariant natural killer T (iNKT) cells are a unique population of lipid-reactive CD1d-restricted innate-like T lymphocytes. Despite being a minor population, they serve as an early source of cytokines and promote immunological crosstalk thus bridging innate and adaptive immunity. Diseases ranging from allergy, autoimmunity, and cancer, as well as infectious diseases, including viral infection, have been reported to be influenced by iNKT cells. However, it remains unclear how iNKT cells are activated during viral infection, as virus-derived lipid antigens have not been reported. Cytokines may activate iNKT cells during infections from influenza and murine cytomegalovirus, although CD1d-dependent activation is evident in other viral infections. Several viruses, such as dengue virus, induce CD1d upregulation, which correlates with iNKT cell activation. In contrast, herpes simplex virus type 1 (HSV-1), human immunodeficiency virus (HIV), Epstein-Barr virus, and human papilloma virus promote CD1d downregulation as a strategy to evade iNKT cell recognition. These observations suggest the participation of a CD1d-dependent process in the activation of iNKT cells in response to viral infection. Endogenous lipid ligands, including phospholipids as well as glycosphingolipids, such as glucosylceramide, have been proposed to mediate iNKT cell activation. Pro-inflammatory signals produced during viral infection may stimulate iNKT cells through enhanced CD1d-dependent endogenous lipid presentation. Furthermore, viral infection may alter lipid composition and inhibit endogenous lipid degradation. Recent advances in this field are reviewed. PMID- 26257746 TI - Functional traits variation explains the distribution of Aextoxicon punctatum (Aextoxicaceae) in pronounced moisture gradients within fog-dependent forest fragments. AB - Climate change and fragmentation are major threats to world forests. Understanding how functional traits related to drought tolerance change across small-scale, pronounced moisture gradients in fragmented forests is important to predict species' responses to these threats. In the case of Aextoxicon punctatum, a dominant canopy tree in fog-dependent rain forest patches in semiarid Chile, we explored how the magnitude, variability and correlation patterns of leaf and xylem vessel traits and hydraulic conductivity varied across soil moisture (SM) gradients established within and among forest patches of different size, which are associated with differences in tree establishment and mortality patterns. Leaf traits varied across soil-moisture gradients produced by fog interception. Trees growing at drier leeward edges showed higher leaf mass per area, trichome and stomatal density than trees from the wetter core and windward zones. In contrast, xylem vessel traits (vessels diameter and density) did not vary producing loss of hydraulic conductivity at drier leeward edges. We also detected higher levels of phenotypic integration and variability at leeward edges. The ability of A. punctatum to modify leaf traits in response to differences in SM availability established over short distances (<500 m) facilitates its persistence in contrasting microhabitats within forest patches. However, xylem anatomy showed limited plasticity, which increases cavitation risk at leeward edges. Greater patch fragmentation, together with fluctuations in irradiance and SM in small patches, could result in higher risk of drought-related tree mortality, with profound impacts on hydrological balances at the ecosystem scale. PMID- 26257747 TI - An organ-specific view on non-host resistance. AB - Non-host resistance (NHR) is the resistance of plants to a plethora of non adapted pathogens and is considered as one of the most robust resistance mechanisms of plants. Studies have shown that the efficiency of resistance in general and NHR in particular could vary in different plant organs, thus pointing to tissue-specific determinants. This was exemplified by research on host and non host interactions of the fungal plant pathogen Magnaporthe oryzae with rice and Arabidopsis, respectively. Thus, rice roots were shown to be impaired in resistance to M. oryzae isolates to which leaves of the same rice cultivar are highly resistant. Moreover, roots of Arabidopsis are also accessible to penetration by M. oryzae while leaves of this non-host plant cannot be infected. We addressed the question whether or not other plant tissues such as the reproductive system also differ in NHR compared to leaves. Inoculation experiments on wheat with different Magnaporthe species forming either a host or non-host type of interaction revealed that NHR was as effective on spikes as on leaves. This finding might pave the way for combatting M. oryzae disease on wheat spikes which has become a serious threat especially in South America. PMID- 26257748 TI - Overexpression of Arabidopsis thaliana ERI, the homolog of C. elegans Enhancer of RNAinterference, leads to enhanced growth. AB - Organisms adopt a wide range of strategies to adapt to change. Gene silencing describes the ability of organisms to modulate the expression of susceptible genes at certain times at the transcriptional or the translational level. In all known eukaryotic organisms 21-nt long short interfering RNAs (siRNAs) are the effector molecules of post-transcriptional gene silencing (PTGS), while 24-nt long siRNAs are involved in PTGS in plants. Mutant studies in Caenorhabditis elegans lead to the identification of the enzyme ERI (Enhancer of RNAinterference) with enhanced PTGS. Although the genes involved in growth vigor and growth rate are still unknown, it becomes clearer that the population of small RNAs plays a role in the very early phase of plant development. To pinpoint the link between growth and siRNAs, the expression of Arabidopsis uni-gene Enhancer of RNAi (ERI) homolog from C. elegans was modulated. Increased degradation of small RNAs was achieved by ectopic AtERI overexpression in planta. Based on global small RNA analysis, AtERI overexpression affects mainly the population of 21 mers, excluding miRNAs. To identify target genes, AtERI gain-of function mutants were analyzed, and differentially abundant small RNAs were identified. Plants with an elevated level of AtERI were bigger in all three light intensities analyzed, indicating an inhibitory function of particular small RNAs in plant growth, with differences in relative growth rates depending on developmental stage and light intensity. Understanding the role of these siRNAs could open new avenues for enhancing plant growth. PMID- 26257750 TI - Camalexin contributes to the partial resistance of Arabidopsis thaliana to the biotrophic soilborne protist Plasmodiophora brassicae. AB - Camalexin has been reported to play defensive functions against several pathogens in Arabidopsis. In this study, we investigated the possible role of camalexin accumulation in two Arabidopsis genotypes with different levels of basal resistance to the compatible eH strain of the clubroot agent Plasmodiophora brassicae. Camalexin biosynthesis was induced in infected roots of both Col-0 (susceptible) and Bur-0 (partially resistant) accessions during the secondary phase of infection. However, the level of accumulation was four-to-seven times higher in Bur-0 than Col-0. This was associated with the enhanced transcription of a set of camalexin biosynthetic P450 genes in Bur-0: CYP71A13, CYP71A12, and CYP79B2. This induction correlated with slower P. brassicae growth in Bur-0 compared to Col-0, thus suggesting a relationship between the levels of camalexin biosynthesis and the different levels of resistance. Clubroot-triggered biosynthesis of camalexin may also participate in basal defense in Col-0, as gall symptoms and pathogen development were enhanced in the pad3 mutant (Col-0 genetic background), which is defective in camalexin biosynthesis. Clubroot and camalexin responses were then studied in Heterogeneous Inbred Families (HIF) lines derived from a cross between Bur-0 and Col-0. The Bur/Col allelic substitution in the region of the previously identified clubroot resistance QTL PbAt5.2 (Chromosome 5) was associated with both the enhanced clubroot-triggered induction of camalexin biosynthesis and the reduced P. brassicae development. Altogether, our results suggest that high levels of clubroot-triggered camalexin biosynthesis play a role in the quantitative control of partial resistance of Arabidopsis to clubroot. PMID- 26257749 TI - TAL effectors and activation of predicted host targets distinguish Asian from African strains of the rice pathogen Xanthomonas oryzae pv. oryzicola while strict conservation suggests universal importance of five TAL effectors. AB - Xanthomonas oryzae pv. oryzicola (Xoc) causes the increasingly important disease bacterial leaf streak of rice (BLS) in part by type III delivery of repeat-rich transcription activator-like (TAL) effectors to upregulate host susceptibility genes. By pathogen whole genome, single molecule, real-time sequencing and host RNA sequencing, we compared TAL effector content and rice transcriptional responses across 10 geographically diverse Xoc strains. TAL effector content is surprisingly conserved overall, yet distinguishes Asian from African isolates. Five TAL effectors are conserved across all strains. In a prior laboratory assay in rice cv. Nipponbare, only two contributed to virulence in strain BLS256 but the strict conservation indicates all five may be important, in different rice genotypes or in the field. Concatenated and aligned, TAL effector content across strains largely reflects relationships based on housekeeping genes, suggesting predominantly vertical transmission. Rice transcriptional responses did not reflect these relationships, and on average, only 28% of genes upregulated and 22% of genes downregulated by a strain are up- and down- regulated (respectively) by all strains. However, when only known TAL effector targets were considered, the relationships resembled those of the TAL effectors. Toward identifying new targets, we used the TAL effector-DNA recognition code to predict effector binding elements in promoters of genes upregulated by each strain, but found that for every strain, all upregulated genes had at least one. Filtering with a classifier we developed previously decreases the number of predicted binding elements across the genome, suggesting that it may reduce false positives among upregulated genes. Applying this filter and eliminating genes for which upregulation did not strictly correlate with presence of the corresponding TAL effector, we generated testable numbers of candidate targets for four of the five strictly conserved TAL effectors. PMID- 26257751 TI - Massive sequencing of Ulmus minor's transcriptome provides new molecular tools for a genus under the constant threat of Dutch elm disease. AB - Elms, especially Ulmus minor and U. americana, are carrying out a hard battle against Dutch elm disease (DED). This vascular wilt disease, caused by Ophiostoma ulmi and O. novo-ulmi, appeared in the twentieth century and killed millions of elms across North America and Europe. Elm breeding and conservation programmes have identified a reduced number of DED tolerant genotypes. In this study, three U. minor genotypes with contrasted levels of tolerance to DED were exposed to several biotic and abiotic stresses in order to (i) obtain a de novo assembled transcriptome of U. minor using 454 pyrosequencing, (ii) perform a functional annotation of the assembled transcriptome, (iii) identify genes potentially involved in the molecular response to environmental stress, and (iv) develop gene based markers to support breeding programmes. A total of 58,429 putative unigenes were identified after assembly and filtering of the transcriptome. 32,152 of these unigenes showed homology with proteins identified in the genome from the most common plant model species. Well-known family proteins and transcription factors involved in abiotic, biotic or both stresses were identified after functional annotation. A total of 30,693 polymorphisms were identified in 7,125 isotigs, a large number of them corresponding to single nucleotide polymorphisms (SNPs; 27,359). In a subset randomly selected for validation, 87% of the SNPs were confirmed. The material generated may be valuable for future Ulmus gene expression, population genomics and association genetics studies, especially taking into account the scarce molecular information available for this genus and the great impact that DED has on elm populations. PMID- 26257752 TI - Coping with drought: stress and adaptive responses in potato and perspectives for improvement. AB - Potato (Solanum tuberosum L.) is often considered as a drought sensitive crop and its sustainable production is threatened due to frequent drought episodes. There has been much research aiming to understand the physiological, biochemical, and genetic basis of drought tolerance in potato as a basis for improving production under drought conditions. The complex phenotypic response of potato plants to drought is conditioned by the interactive effects of the plant's genotypic potential, developmental stage, and environment. Effective crop improvement for drought tolerance will require the pyramiding of many disparate characters, with different combinations being appropriate for different growing environments. An understanding of the interaction between below ground water uptake by the roots and above ground water loss from the shoot system is essential. The development of high throughput precision phenotyping platforms is providing an exciting new tool for precision screening, which, with the incorporation of innovative screening strategies, can aid the selection and pyramiding of drought-related genes appropriate for specific environments. Outcomes from genomics, proteomics, metabolomics, and bioengineering advances will undoubtedly compliment conventional breeding strategies and presents an alternative route toward development of drought tolerant potatoes. This review presents an overview of past research activity, highlighting recent advances with examples from other crops and suggesting future research directions. PMID- 26257753 TI - Genetic control of inflorescence architecture in legumes. AB - The architecture of the inflorescence, the shoot system that bears the flowers, is a main component of the huge diversity of forms found in flowering plants. Inflorescence architecture has also a strong impact on the production of fruits and seeds, and on crop management, two highly relevant agronomical traits. Elucidating the genetic networks that control inflorescence development, and how they vary between different species, is essential to understanding the evolution of plant form and to being able to breed key architectural traits in crop species. Inflorescence architecture depends on the identity and activity of the meristems in the inflorescence apex, which determines when flowers are formed, how many are produced and their relative position in the inflorescence axis. Arabidopsis thaliana, where the genetic control of inflorescence development is best known, has a simple inflorescence, where the primary inflorescence meristem directly produces the flowers, which are thus borne in the main inflorescence axis. In contrast, legumes represent a more complex inflorescence type, the compound inflorescence, where flowers are not directly borne in the main inflorescence axis but, instead, they are formed by secondary or higher order inflorescence meristems. Studies in model legumes such as pea (Pisum sativum) or Medicago truncatula have led to a rather good knowledge of the genetic control of the development of the legume compound inflorescence. In addition, the increasing availability of genetic and genomic tools for legumes is allowing to rapidly extending this knowledge to other grain legume crops. This review aims to describe the current knowledge of the genetic network controlling inflorescence development in legumes. It also discusses how the combination of this knowledge with the use of emerging genomic tools and resources may allow rapid advances in the breeding of grain legume crops. PMID- 26257756 TI - Changing environmental conditions and applying organic fertilizers in Origanum vulgare L. AB - Any improvement in agricultural systems that results in higher production should also reduce negative environmental impacts and enhance sustainability. The aim of this research was to investigate the effect of two different production systems, one open-field and the other shade-enclosure with four bocashi doses, in order to find the best environmental option in terms of yield, physiological and morphometric characteristics in one oregano (Origanum vulgare L.) cultivar. In this study a completely randomized block design was used with four replications and evaluated for photosynthetic and transpiration rate, stomatal conductance, chlorophyll, leaf area and temperature, aerial and roots fresh and dry biomass, fresh and dry yield. The results showed that oregano adapted best to the shade enclosure with increase yield of fresh and dry leaf weight of 165% and 118%, respectively, when compared to open-field. Also, higher doses of bocashi improved yield in both environments but more so in shade-enclosure. Soil moisture retention was higher in shade-enclosure which was reflected in physiological variables for soil matric potential, transpiration, stomatal conductivity, photosynthesis being significantly higher in shade-enclosure compared to open field, thus improving yield. It seems that oregano plants can be grown and perform better under shade-enclosure than open-field and bocashi is a suitable organic fertilizer. PMID- 26257755 TI - Identification of novel drought-tolerant-associated SNPs in common bean (Phaseolus vulgaris). AB - Common bean (Phaseolus vulgaris L.) is a leguminous in high demand for human nutrition and a very important agricultural product. Production of common bean is constrained by environmental stresses such as drought. Although conventional plant selection has been used to increase production yield and stress tolerance, drought tolerance selection based on phenotype is complicated by associated physiological, anatomical, cellular, biochemical, and molecular changes. These changes are modulated by differential gene expression. A common method to identify genes associated with phenotypes of interest is the characterization of Single Nucleotide Polymorphims (SNPs) to link them to specific functions. In this work, we selected two drought-tolerant parental lines from Mesoamerica, Pinto Villa, and Pinto Saltillo. The parental lines were used to generate a population of 282 families (F3:5) and characterized by 169 SNPs. We associated the segregation of the molecular markers in our population with phenotypes including flowering time, physiological maturity, reproductive period, plant, seed and total biomass, reuse index, seed yield, weight of 100 seeds, and harvest index in three cultivation cycles. We observed 83 SNPs with significant association (p < 0.0003 after Bonferroni correction) with our quantified phenotypes. Phenotypes most associated were days to flowering and seed biomass with 58 and 44 associated SNPs, respectively. Thirty-seven out of the 83 SNPs were annotated to a gene with a potential function related to drought tolerance or relevant molecular/biochemical functions. Some SNPs such as SNP28 and SNP128 are related to starch biosynthesis, a common osmotic protector; and SNP18 is related to proline biosynthesis, another well-known osmotic protector. PMID- 26257754 TI - Role of proline in cell wall synthesis and plant development and its implications in plant ontogeny. AB - Proline is a proteogenic amino acid and accumulates both under stress and non stress conditions as a beneficial solute in plants. Recent discoveries point out that proline plays an important role in plant growth and differentiation across life cycle. It is a key determinant of many cell wall proteins that plays important roles in plant development. The role of extensins, arabinogalactan proteins and hydroxyproline- and proline-rich proteins as important components of cell wall proteins that play pivotal roles in cell wall signal transduction cascades, plant development and stress tolerance is discussed in this review. Molecular insights are also provided here into the plausible roles of proline transporters modulating key events in plant development. In addition, the roles of proline during seed developmental transitions including storage protein synthesis are discussed. PMID- 26257757 TI - Acetylation of cell wall is required for structural integrity of the leaf surface and exerts a global impact on plant stress responses. AB - The epidermis on leaves protects plants from pathogen invasion and provides a waterproof barrier. It consists of a layer of cells that is surrounded by thick cell walls, which are partially impregnated by highly hydrophobic cuticular components. We show that the Arabidopsis T-DNA insertion mutants of REDUCED WALL ACETYLATION 2 (rwa2), previously identified as having reduced O-acetylation of both pectins and hemicelluloses, exhibit pleiotrophic phenotype on the leaf surface. The cuticle layer appeared diffused and was significantly thicker and underneath cell wall layer was interspersed with electron-dense deposits. A large number of trichomes were collapsed and surface permeability of the leaves was enhanced in rwa2 as compared to the wild type. A massive reprogramming of the transcriptome was observed in rwa2 as compared to the wild type, including a coordinated up-regulation of genes involved in responses to abiotic stress, particularly detoxification of reactive oxygen species and defense against microbial pathogens (e.g., lipid transfer proteins, peroxidases). In accordance, peroxidase activities were found to be elevated in rwa2 as compared to the wild type. These results indicate that cell wall acetylation is essential for maintaining the structural integrity of leaf epidermis, and that reduction of cell wall acetylation leads to global stress responses in Arabidopsis. PMID- 26257758 TI - EXTENSIN18 is required for full male fertility as well as normal vegetative growth in Arabidopsis. AB - EXTENSINS (EXTs) are a 65-member subfamily of hydroxyproline-rich glycoproteins (HRGPs) of which 20 putatively form crosslinking networks in the cell wall. These 20 classical EXTs are involved at the start of new wall assembly as evidenced by a requirement for EXT3 during cytokinesis, and the ability of some EXTs to polymerize in vitro into dendritic patterns. EXT3 was previously shown to form pulcherosine (three Tyrosines) cross-links. Little direct data exists on the other 19 classical EXTs. Here, we describe the phenotypes of ext18 mutants and rescued progeny as well as associated expression profiles of all 20 classical EXT genes. We found that EXT18 is required for full male fertility, as well as for normal vegetative growth. EXT18 has potential to form crosslinking networks via di-iso-di-tyrosine (four Tyrosines) covalent bonds, and not via pulcherosine due to deficit of lone Tyrosines. This together with ext18 defective pollen grains and pollen tubes, and reduced plant size, suggests that EXT18-type EXTs are important contributors to wall integrity, in pollen and other rapidly extending walls. The data also show that a knockout of EXT18 had a pleiotropic affect on the expression of several EXTs, as did the reintroduction of the native EXT18 gene, thus supporting the thesis that transcription of groups of EXTs are co regulated and work in different combinations to make distinctive inputs into wall assembly of different cell types. These insights contribute to basic knowledge of cell wall self-assembly in different cell types, and potentially enable biotechnological advances in biomass increase and plant fertility control. PMID- 26257759 TI - Commentary: Toward a more physiologically and evolutionarily relevant definition of metal hyperaccumulation in plants. PMID- 26257760 TI - Maize miRNA and target regulation in response to hormone depletion and light exposure during somatic embryogenesis. AB - Maize somatic embryogenesis (SE) is induced from the immature zygotic embryo in darkness and under the appropriate hormones' levels. Small RNA expression is reprogrammed and certain miRNAs become particularly enriched during induction while others, characteristic to the zygotic embryo, decrease. To explore the impact of different environmental cues on miRNA regulation in maize SE, we tested specific miRNA abundance and their target gene expression in response to photoperiod and hormone depletion for two different maize cultivars (VS-535 and H 565). The expression levels of miR156, miR159, miR164, miR168, miR397, miR398, miR408, miR528, and some predicted targets (SBP23, GA-MYB, CUC2, AGO1c, LAC2, SOD9, GR1, SOD1A, PLC) were examined upon staged hormone depletion in the presence of light photoperiod or darkness. Almost all examined miRNA, except miR159, increased upon hormone depletion, regardless photoperiod absence/presence. miR528, miR408, and miR398 changed the most. On the other hand, expression of miRNA target genes was strongly regulated by the photoperiod exposure. Stress-related miRNA targets showed greater differences between cultivars than development-related targets. miRNA/target inverse relationship was more frequently observed in darkness than light. Interestingly, miR528, but not miR159, miR168 or miR398, was located on polyribosome fractions suggesting a role for this miRNA at the level of translation. Overall our results demonstrate that hormone depletion exerts a great influence on specific miRNA expression during plant regeneration independently of light. However, their targets are additionally influenced by the presence of photoperiod. The reproducibility or differences observed for particular miRNA-target regulation between two different highly embryogenic genotypes provide clues for conserved miRNA roles within the SE process. PMID- 26257761 TI - Mitogen-activated protein kinase cascades in Vitis vinifera. AB - Protein phosphorylation is one of the most important mechanisms to control cellular functions in response to external and endogenous signals. Mitogen activated protein kinases (MAPK) are universal signaling molecules in eukaryotes that mediate the intracellular transmission of extracellular signals resulting in the induction of appropriate cellular responses. MAPK cascades are composed of four protein kinase modules: MAPKKK kinases (MAPKKKKs), MAPKK kinases (MAPKKKs), MAPK kinases (MAPKKs), and MAPKs. In plants, MAPKs are activated in response to abiotic stresses, wounding, and hormones, and during plant pathogen interactions and cell division. In this report, we performed a complete inventory of MAPK cascades genes in Vitis vinifera, the whole genome of which has been sequenced. By comparison with MAPK, MAPK kinases, MAPK kinase kinases and MAPK kinase kinase kinase kinase members of Arabidopsis thaliana, we revealed the existence of 14 MAPKs, 5 MAPKKs, 62 MAPKKKs, and 7 MAPKKKKs in Vitis vinifera. We identified orthologs of V. vinifera putative MAPKs in different species, and ESTs corresponding to members of MAPK cascades in various tissues. This work represents the first complete inventory of MAPK cascades in V. vinifera and could help elucidate the biological and physiological functions of these proteins in V. vinifera. PMID- 26257762 TI - Commentary: Extracellular peptidase hunting for improvement of protein production in plant cells and roots. PMID- 26257763 TI - Identification of protein N-termini in Cyanophora paradoxa cyanelles: transit peptide composition and sequence determinants for precursor maturation. AB - Glaucophyta, rhodophyta, and chloroplastida represent the three main evolutionary lineages that diverged from a common ancestor after primary endosymbiosis. Comparative analyses between members of these three lineages are a rich source of information on ancestral plastid features. We analyzed the composition and the cleavage site of cyanelle transit peptides from the glaucophyte Cyanophora paradoxa by terminal amine labeling of substrates (TAILS), and compared their characteristics to those of representatives of the chloroplastida. Our data show that transit peptide architecture is similar between members of these two lineages. This entails a comparable modular structure, an overrepresentation of serine or alanine and similarities in the amino acid composition around the processing peptidase cleavage site. The most distinctive difference is the overrepresentation of phenylalanine in the N-terminal 1-10 amino acids of cyanelle transit peptides. A quantitative proteome analysis with periplasm-free cyanelles identified 42 out of 262 proteins without the N-terminal phenylalanine, suggesting that the requirement for phenylalanine in the N-terminal region is not absolute. Proteins in this set are on average of low abundance, suggesting that either alternative import pathways are operating specifically for low abundance proteins or that the gene model annotation is incorrect for proteins with fewer EST sequences. We discuss these two possibilities and provide examples for both interpretations. PMID- 26257764 TI - Pollination triggers female gametophyte development in immature Nicotiana tabacum flowers. AB - In Nicotiana tabacum, female gametophytes are not fully developed at anthesis, but flower buds pollinated 12 h before anthesis produce mature embryo sacs. We investigated several pollination-associated parameters in N. tabacum flower buds to determine the developmental timing of important events in preparation for successful fertilization. First, we performed hand pollinations in flowers from stages 4 to 11 to study at which developmental stage pollination would produce fruits. A Peroxtesmo test was performed to correlate peroxidase activity on the stigma surface, indicative of stigma receptivity, with fruit set. Pollen tube growth and female gametophyte development were microscopically analyzed in pistils of different developmental stages. Fruits were obtained only after pollinations of flower buds at late stage 7 and older; fruit weight and seed germination capacity increased as the developmental stage of the pollinated flower approached anthesis. Despite positive peroxidase activity and pollen tube growth, pistils at stages 5 and 6 were unable to produce fruits. At late stage 7, female gametophytes were undergoing first mitotic division. After 24 h, female gametophytes of unpollinated pistils were still in the end of the first division, whereas those of pollinated pistils showed egg cells. RT-qPCR assay showed that the expression of the NtEC1 gene, a marker of egg cell development, is considerably higher in pollinated late stage 7 ovaries compared with unpollinated ovaries. To test whether ethylene is the signal eliciting female gametophyte maturation, the expression of ACC synthase was examined in unpollinated and pollinated stage 6 and late stage 7 stigmas/styles. Pollination induced NtACS expression in stage 6 pistils, which are unable to produce fruits. Our results show that pollination is a stimulus capable of triggering female gametophyte development in immature tobacco flowers and suggests the existence of a yet undefined signal sensed by the pistil. PMID- 26257766 TI - Dissection of drought response of modern and underutilized wheat varieties according to Passioura's yield-water framework. AB - Trait-based breeding is essential to improve wheat yield, particularly when stress adaptation is targeted. A set of modern and underutilized wheat genotypes was examined in a 2-year field experiment with distinct seasonal water supply. Yield formation and drought response strategies were analyzed in relation to components of Passioura's yield-water framework based on phenological, morphological, physiological, and root characteristics. Limited water supply resulted in 60% yield loss and substantially lower water use (37%), water use efficiency (32.6%), and harvest index (14%). Phenology and root length density were key determinants of water use. Late flowering underutilized wheat species with large root system and swift ground coverage showed greatest water use. Leaf chlorophyll concentration and stomata conductance were higher in modern cultivars, supporting their high biomass growth and superior water use efficiency. While, lower chlorophyll concentration and stomata conductance of underutilized wheats indicated a water saving strategy with an intrinsic limitation of potential growth. Harvest index was strongly dependent on phenology and yield components. Optimized flowering time, reduced tillering, and strong grain sink of modern cultivars explained higher harvest index compared to underutilized wheats. Cluster analysis revealed the consistent differentiation of underutilized and modern wheats based on traits underlying Passioura's yield water framework. We identified physiological and root traits within modern cultivars to be targeted for trait-based crop improvement under water-limited conditions. High capacity of water use in underutilized genetic resources is related to yield-limiting phenological and morphological traits, constraining their potential role for better drought resistance. Still some genetic resources provide adaptive features for stress resistance compatible with high yield as revealed by high harvest index under drought of Khorasan wheat. PMID- 26257765 TI - In vivo spectroscopy and NMR metabolite fingerprinting approaches to connect the dynamics of photosynthetic and metabolic phenotypes in resurrection plant Haberlea rhodopensis during desiccation and recovery. AB - The resurrection plant Haberlea rhodopensis was used to study dynamics of drought response of photosynthetic machinery parallel with changes in primary metabolism. A relation between leaf water content and photosynthetic performance was established, enabling us to perform a non-destructive evaluation of the plant water status during stress. Spectroscopic analysis of photosynthesis indicated that, at variance with linear electron flow (LEF) involving photosystem (PS) I and II, cyclic electron flow around PSI remains active till almost full dry state at the expense of the LEF, due to the changed protein organization of photosynthetic apparatus. We suggest that, this activity could have a photoprotective role and prevent a complete drop in adenosine triphosphate (ATP), in the absence of LEF, to fuel specific energy-dependent processes necessary for the survival of the plant, during the late states of desiccation. The NMR fingerprint shows the significant metabolic changes in several pathways. Due to the declining of LEF accompanied by biosynthetic reactions during desiccation, a reduction of the ATP pool during drought was observed, which was fully and quickly recovered after plants rehydration. We found a decline of valine accompanied by lipid degradation during stress, likely to provide alternative carbon sources for sucrose accumulation at late stages of desiccation. This accumulation, as well as the increased levels of glycerophosphodiesters during drought stress could provide osmoprotection to the cells. PMID- 26257767 TI - Rapid estimation of nutritional elements on citrus leaves by near infrared reflectance spectroscopy. AB - Sufficient nutrient application is one of the most important factors in producing quality citrus fruits. One of the main guides in planning citrus fertilizer programs is by directly monitoring the plant nutrient content. However, this requires analysis of a large number of leaf samples using expensive and time consuming chemical techniques. Over the last 5 years, it has been demonstrated that it is possible to quantitatively estimate certain nutritional elements in citrus leaves by using the spectral reflectance values, obtained by using near infrared reflectance spectroscopy (NIRS). This technique is rapid, non destructive, cost-effective and environmentally friendly. Therefore, the estimation of macro and micronutrients in citrus leaves by this method would be beneficial in identifying the mineral status of the trees. However, to be used effectively NIRS must be evaluated against the standard techniques across different cultivars. In this study, NIRS spectral analysis, and subsequent nutrient estimations for N, K, Ca, Mg, B, Fe, Cu, Mn, and Zn concentration, were performed using 217 leaf samples from different citrus trees species. Partial least square regression and different pre-processing signal treatments were used to generate the best estimation against the current best practice techniques. It was verified a high proficiency in the estimation of N (Rv = 0.99) and Ca (Rv = 0.98) as well as achieving acceptable estimation for K, Mg, Fe, and Zn. However, no successful calibrations were obtained for the estimation of B, Cu, and Mn. PMID- 26257768 TI - Remote homology and the functions of metagenomic dark matter. AB - Predicted open reading frames (ORFs) that lack detectable homology to known proteins are termed ORFans. Despite their prevalence in metagenomes, the extent to which ORFans encode real proteins, the degree to which they can be annotated, and their functional contributions, remain unclear. To gain insights into these questions, we applied sensitive remote-homology detection methods to functionally analyze ORFans from soil, marine, and human gut metagenome collections. ORFans were identified, clustered into sequence families, and annotated through profile profile comparison to proteins of known structure. We found that a considerable number of metagenomic ORFans (73,896 of 484,121, 15.3%) exhibit significant remote homology to structurally characterized proteins, providing a means for ORFan functional profiling. The extent of detected remote homology far exceeds that obtained for artificial protein families (1.4%). As expected for real genes, the predicted functions of ORFans are significantly similar to the functions of their gene neighbors (p < 0.001). Compared to the functional profiles predicted through standard homology searches, ORFans show biologically intriguing differences. Many ORFan-enriched functions are virus-related and tend to reflect biological processes associated with extreme sequence diversity. Each environment also possesses a large number of unique ORFan families and functions, including some known to play important community roles such as gut microbial polysaccharide digestion. Lastly, ORFans are a valuable resource for finding novel enzymes of interest, as we demonstrate through the identification of hundreds of novel ORFan metalloproteases that all possess a signature catalytic motif despite a general lack of similarity to known proteins. Our ORFan functional predictions are a valuable resource for discovering novel protein families and exploring the boundaries of protein sequence space. All remote homology predictions are available at http://doxey.uwaterloo.ca/ORFans. PMID- 26257769 TI - Post-transcriptional regulation of BRCA1 through its coding sequence by the miR 15/107 group of miRNAs. AB - MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by degrading their RNA targets or by repressing the translation of messenger RNAs (mRNAs). Initially thought to primarily target the 3' untranslated region (3'UTR) of mRNAs, miRNAs have since been shown to also target the 5'UTR and coding sequence (CDS). In this work, we focus on the post transcriptional regulation of the BRCA1 gene, a major tumor suppressor and regulator of double-stranded break DNA repair and show that its mRNA is targeted by many members of the miR-15/107 group at a site located within the CDS. Ectopic expression of these miRNAs across a panel of nine cell lines demonstrated widespread suppression of BRCA1 mRNA levels. Additionally, by cloning a putative target site from BRCA1's amino acid CDS into a luciferase reporter plasmid we confirmed the direct interaction of these miRNAs with this BRCA1 target. We also examined the relationship between ectopic expression of these targeting miRNAs and BRCA1 protein levels in immortalized pancreatic epithelium (hTERT-HPNE), colorectal adenocarcinoma (HCT-116) and pancreatic adenocarcinoma (MIA PaCa-2) cell lines and found protein abundance to be variably regulated in a cell-type specific manner that was not necessarily concordant with mRNA transcript availability. Our findings reveal a previously unrecognized aspect of BRCA1's miRNA-mediated post-transcriptional regulation, namely the targeting of its amino acid coding region by the miR-15/107 group of miRNAs. The resulting regulation is apparently complex and cell-specific, an observation that may have implications for BRCA1-mediated DNA repair across tissue types. PMID- 26257770 TI - Interaction between oxytocin receptor DNA methylation and genotype is associated with risk of postpartum depression in women without depression in pregnancy. AB - Postpartum depression (PPD) affects up to 19% of women, negatively impacting maternal and infant health. Reductions in plasma oxytocin levels have been associated with PPD and heritability studies have established a genetic contribution. Epigenetic regulation of the oxytocin receptor gene (OXTR) has been demonstrated and we hypothesized that individual epigenetic variability at OXTR may impact the development of PPD and that such variability may be central to predicting risk. This case-control study is nested within the Avon Longitudinal Study of Parents and Children and included 269 cases with PPD and 276 controls matched on age group, parity, and presence or absence of depressive symptoms in pregnancy as assessed by the Edinburgh Postnatal Depression Scale. OXTR DNA methylation (CpG site -934) and genotype (rs53576 and rs2254298) were assayed from DNA extracted from blood collected during pregnancy. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of elevated symptoms of PPD with genotype, methylation, and their interaction adjusted for psychosocial factors (n = 500). There was evidence of an interaction between rs53576 and methylation in the OXTR gene amongst women who did not have depression prenatally but developed PPD (p interaction = 0.026, adjusted for covariates, n = 257). Those women with GG genotype showed 2.63 greater odds of PPD for every 10% increase in methylation level (95% CI: 1.37, 5.03), whereas methylation was unrelated to PPD amongst "A" carriers (OR = 1.00, 95% CI: 0.58, 1.73). There was no such interaction among women with PPD and prenatal depression. These data indicate that epigenetic variation that decreases expression of OXTR in a susceptible genotype may play a contributory role in the etiology of PPD. PMID- 26257771 TI - How well do whole exome sequencing results correlate with medical findings? A study of 89 Mayo Clinic Biobank samples. AB - Whole exome sequencing (WES) is increasingly being used for diagnosis without adequate information on predictive characteristics of reportable variants typically found on any given individual and correlation with clinical phenotype. In this study, we performed WES on 89 deceased individuals (mean age at death 74 years, range 28-93) from the Mayo Clinic Biobank. Significant clinical diagnoses were abstracted from electronic medical record via chart review. Variants [Single Nucleotide Variant (SNV) and insertion/deletion] were filtered based on quality (accuracy >99%, read-depth >20, alternate-allele read-depth >5, minor-allele frequency <0.1) and available HGMD/OMIM phenotype information. Variants were defined as Tier-1 (nonsense, splice or frame-shifting) and Tier-2 (missense, predicted-damaging) and evaluated in 56 ACMG-reportable genes, 57 cancer predisposition genes, along with examining overall genotype-phenotype correlations. Following variant filtering, 7046 total variants were identified (~79/person, 644 Tier-1, 6402 Tier-2), 161 among 56 ACMG-reportable genes (~1.8/person, 13 Tier-1, 148 Tier-2), and 115 among 57 cancer-predisposition genes (~1.3/person, 3 Tier-1, 112 Tier-2). The number of variants across 57 cancer-predisposition genes did not differentiate individuals with/without invasive cancer history (P > 0.19). Evaluating genotype-phenotype correlations across the exome, 202(3%) of 7046 filtered variants had some evidence for phenotypic correlation in medical records, while 3710(53%) variants had no phenotypic correlation. The phenotype associated with the remaining 44% could not be assessed from a typical medical record review. These data highlight significant continued challenges in the ability to extract medically meaningful predictive results from WES. PMID- 26257772 TI - Heating and ultraviolet light activate anti-stress gene functions in humans. AB - Different environmental factors (i.e., toxins, heavy metals, ultraviolet (UV) rays, and X-radiation) cause damage to DNA, cell membranes and other organelles and induce oxidative stress, which results in the excessive production of reactive oxygen species (ROS) by phagocytes. All types of cell stress are accompanied by the activation of anti-stress genes that can suppress ROS synthesis. We hypothesized that different environmental factors would affect organisms through the activation of anti-stress genes by autologous serum (AS) proteins, followed by the synthesis of molecules that increase cell resistance to oxidative stress. The goal of this work was to study the influence of AS on ROS production by peripheral blood neutrophils isolated from donors in different age groups. Neutrophils were isolated from 59 donors (38-94 years old). AS was heated at 100 degrees C for 30 s. or irradiated by UV light at 200-280 nm and 8 W for 10 min. Neutrophils were exposed to heat shock at 42 degrees C for 1 min. (short term heating stress) or 43 degrees C for 10 min., followed by the determination of the chemiluminescence reaction induced by zymosan. AS can increase or decrease ROS production by neutrophils depending on the structure of the proteins in the serum; these structures can be changed by heating or UV treatment and the temperature of their interaction (4 or 37 degrees C). We propose that the effect of environmental factors on AS proteins can cause an adverse increase in oxidative stress levels due to the functional reduction of anti-stress genes. We found a negative correlation between the quantity of intracellular Hsp70 and levels of intracellular ROS production following 10 min of heat shock at 43 degrees C. Short-term heating stress (1 min) at 42 degrees C was followed by a prominent reduction in ROS production. This effect may be a result of the impact of the hormone adrenaline on the functions of anti-stress genes. Indeed, the same effect was observed after treatment of the neutrophils with adrenaline at concentrations of 10(-4) and 10(-5) M. In contrast, dexamethasone from the other stress hormone group did not evoke the same effect at the same concentrations. PMID- 26257773 TI - Control of competence by related non-coding csRNAs in Streptococcus pneumoniae R6. AB - The two-component regulatory system CiaRH of Streptococcus pneumoniae is involved in beta-lactam resistance, maintenance of cell integrity, bacteriocin production, host colonization, virulence, and competence. The response regulator CiaR controls, among other genes, expression of five highly similar small non-coding RNAs, designated csRNAs. These csRNAs control competence development by targeting comC, encoding the precursor of the competence stimulating peptide, which is essential to initiate the regulatory cascade leading to competence. In addition, another gene product of the CiaR regulon, the serine protease HtrA, is also involved in competence control. In the absence of HtrA, five csRNAs could suppress competence, but one csRNA alone was not effective. To determine if all csRNAs are needed, reporter gene fusions to competence genes were used to monitor competence gene expression in the presence of different csRNAs. These experiments showed that two csRNAs were not enough to prevent competence, but combinations of three csRNAs, csRNA1,2,3, or csRNA1,2,4 were sufficient. In S. pneumoniae strains expressing only csRNA5, a surprising positive effect was detected on the level of early competence gene expression. Hence, the role of the csRNAs in competence regulation is more complex than anticipated. Mutations in comC (comC8) partially disrupting predicted complementarity to the csRNAs led to competence even in the presence of all csRNAs. Reconstitution of csRNA complementarity to comC8 restored competence suppression. Again, more than one csRNA was needed. In this case, even two mutated csRNAs complementary to comC8, csRNA1-8 and csRNA2-8, were suppressive. In conclusion, competence in S. pneumoniae is additively controlled by the csRNAs via post-transcriptional regulation of comC. PMID- 26257774 TI - Dose-dependent effects of mTOR inhibition on weight and mitochondrial disease in mice. AB - Rapamycin extends lifespan and attenuates age-related pathologies in mice when administered through diet at 14 parts per million (PPM). Recently, we reported that daily intraperitoneal injection of rapamycin at 8 mg/kg attenuates mitochondrial disease symptoms and progression in the Ndufs4 knockout mouse model of Leigh Syndrome. Although rapamycin is a widely used pharmaceutical agent dosage has not been rigorously examined and no dose-response profile has been established. Given these observations we sought to determine if increased doses of oral rapamycin would result in more robust impact on mTOR driven parameters. To test this hypothesis, we compared the effects of dietary rapamycin at doses ranging from 14 to 378 PPM on developmental weight in control and Ndufs4 knockout mice and on health and survival in the Ndufs4 knockout model. High dose rapamycin was well tolerated, dramatically reduced weight gain during development, and overcame gender differences. The highest oral dose, approximately 27-times the dose shown to extend murine lifespan, increased survival in Ndufs4 knockout mice similarly to daily rapamycin injection without observable adverse effects. These findings have broad implications for the effective use of rapamycin in murine studies and for the translational potential of rapamycin in the treatment of mitochondrial disease. This data, further supported by a comparison of available literature, suggests that 14 PPM dietary rapamycin is a sub-optimal dose for targeting mTOR systemically in mice. Our findings suggest that the role of mTOR in mammalian biology may be broadly underestimated when determined through treatment with rapamycin at commonly used doses. PMID- 26257775 TI - FOXP3 is a promising and potential candidate gene in generalised vitiligo susceptibility. PMID- 26257777 TI - Algorithmic Mechanism Design of Evolutionary Computation. AB - We consider algorithmic design, enhancement, and improvement of evolutionary computation as a mechanism design problem. All individuals or several groups of individuals can be considered as self-interested agents. The individuals in evolutionary computation can manipulate parameter settings and operations by satisfying their own preferences, which are defined by an evolutionary computation algorithm designer, rather than by following a fixed algorithm rule. Evolutionary computation algorithm designers or self-adaptive methods should construct proper rules and mechanisms for all agents (individuals) to conduct their evolution behaviour correctly in order to definitely achieve the desired and preset objective(s). As a case study, we propose a formal framework on parameter setting, strategy selection, and algorithmic design of evolutionary computation by considering the Nash strategy equilibrium of a mechanism design in the search process. The evaluation results present the efficiency of the framework. This primary principle can be implemented in any evolutionary computation algorithm that needs to consider strategy selection issues in its optimization process. The final objective of our work is to solve evolutionary computation design as an algorithmic mechanism design problem and establish its fundamental aspect by taking this perspective. This paper is the first step towards achieving this objective by implementing a strategy equilibrium solution (such as Nash equilibrium) in evolutionary computation algorithm. PMID- 26257776 TI - Neuroactive compounds obtained from arthropod venoms as new therapeutic platforms for the treatment of neurological disorders. AB - The impact of neurological disorders in society is growing with alarming estimations for an incidence increase in the next decades. These disorders are generally chronic and can affect individuals early during productive life, imposing real limitations on the performance of their social roles. Patients can have their independence, autonomy, freedom, self-image, and self-confidence affected. In spite of their availability, drugs for the treatment of these disorders are commonly associated with side effects, which can vary in frequency and severity. Currently, no effective cure is known. Nowadays, the biopharmaceutical research community widely recognizes arthropod venoms as a rich source of bioactive compounds, providing a plethora of possibilities for the discovery of new neuroactive compounds, opening up novel and attractive opportunities in this field. Several identified molecules with a neuropharmacological profile can act in the central nervous system on different neuronal targets, rendering them useful tools for the study of neurological disorders. In this context, this review aims to describe the current main compounds extracted from arthropod venoms for the treatment of five major existing neurological disorders: stroke, Alzheimer's disease, epilepsy, Parkinson's disease, and pathological anxiety. PMID- 26257778 TI - Choledochal Cyst in Adults: Etiopathogenesis, Presentation, Management, and Outcome-Case Series and Review. AB - Background. Choledochal cyst, a rare congenital cystic dilatation of biliary tree, is uncommon in adults. Their presentations differ from children and surgical management has evolved. Methods. A retrospective review of the records of all the patients above 15 years, who underwent therapeutic intervention in our hospital, was carried out. Results. Ten cases of choledochal cyst were found; 8 female, with mean age 31 years. These included 8 cases of Todani type I and one case each of type II and type III. The predominant symptoms were abdominal pain and jaundice. Abdominal mass and past history of cholangitis and pancreatitis were seen in 2 patients. Investigations included ultrasound in 8 patients, CT in 7, ERCP in 3, and MRCP in 5. Surgical intervention included complete excision of the cyst with hepaticojejunostomy and cholecystectomy (type I), excision of the diverticulum (type II), and ERCP sphincterotomy (type III). Malignancy was not seen in any patients. The long-term postoperative complications included cholangitis in two patients. Conclusion. Choledochal cyst is rare in adults. The typical triad of abdominal pain, jaundice, and mass is uncommon in adults. The surgical strategy aims for single stage complete excision of the cyst with hepaticojejunostomy. PMID- 26257779 TI - Insulin Resistance of Normal Weight Central Obese Adolescents in Korea Stratified by Waist to Height Ratio: Results from the Korea National Health and Nutrition Examination Surveys 2008-2010. AB - Background. To evaluate insulin resistance of normal weight central obese 13-18 year-old male and female adolescents stratified by waist to height ratio (WHR). Methods. Data were obtained from the Korea National Health and Nutrition Examination Survey (K-NHANES) conducted during 2008-2010. Central obesity was defined as that in the upper quartile of age and sex specific WHR. Subjects were classified into no central obesity normal weight (NW), central obesity normal weight (CONW), no central obesity overweight (OW), and central obesity overweight (COOW). Results. The prevalence of CONW was 9.6% (83/832) in female and 7.0% (61/909) in male. CONW showed higher levels of insulin (P < 0.006), HOMA-IR (P < 0.006), and ALT (P < 0.001) than NW in female. CONW had higher levels of insulin (P < 0.0001), HOMA-IR (P < 0.0001), and WBC count (P < 0.021) and lower level of HDL (P < 0.0001) than NW in male. WHR and BMI had similar significant correlations with MS components. CONW showed 2.5 times (95% confidence interval, 1.21-5.00) more likelihood to have high insulin resistance than NW in male. Conclusions. Screening for central obesity using WHR in clinical setting is recommended. PMID- 26257780 TI - An Intensive Lifestyle Intervention Is an Effective Treatment of Morbid Obesity: The TRAMOMTANA Study-A Two-Year Randomized Controlled Clinical Trial. AB - Bariatric surgery is currently the most effective therapy to induce weight loss in morbidly obese patients. Objective. This controlled, clinical trial with a two year intervention was aimed at comparing the efficacy of two nonsurgical approaches versus bariatric surgery, on body weight changes and metabolic parameters in morbidly obese patients. Methods. Patients were randomized to an Intensive Lifestyle Intervention (ILI) (n = 60) or Conventional Obesity Therapy (COT) (n = 46). The ILI group received behavioral therapy and nutritional counseling. The COT group received standard medical treatment. They were compared with a third group, Surgical Obesity Group (SOG) (n = 37). Results. Patients who received ILI had a greater percentage of weight loss than patients receiving COT (-11.3% versus -1.6%; p < 0.0044). Interestingly 31.4% of patients included in the ILI group were no longer morbidly obese after just six months of intervention, increasing to 44.4% after 24 months of intervention. The percentage weight loss in SOG was -29.6% after that same period of time. Conclusions. ILI was associated with significant weight loss when compared to COT, in a group of patients with obesity. An ILI approach could be an alternative therapy to patients with obesity, who are not candidates to undergo bariatric surgery. This trial is registered with EudraCT 2009-013737-24. PMID- 26257781 TI - Ghrelin's Effects on Proinflammatory Cytokine Mediated Apoptosis and Their Impact on beta-Cell Functionality. AB - Ghrelin is a peptidic hormone, which stimulates cell proliferation and inhibits apoptosis in several tissues, including pancreas. In preclinical stage of type 1 diabetes, proinflammatory cytokines generate a destructive environment for beta cells known as insulitis, which results in loss of beta-cell mass and impaired insulin secretion, leading to diabetes. Our aim was to demonstrate that ghrelin could preserve beta-cell viability, turnover rate, and insulin secretion acting as a counter balance of cytokines. In the present work we reproduced proinflammatory milieu found in insulitis stage by treating murine cell line INS 1E and rat islets with a cytokine cocktail including IL-1beta, IFNgamma, and TNFalpha and/or ghrelin. Several proteins involved in survival pathways (ERK 1/2 and Akt/PKB) and apoptosis (caspases and Bcl-2 protein family and endoplasmic reticulum stress markers) as well as insulin secretion were analyzed. Our results show that ghrelin alone has no remarkable effects on beta-cells in basal conditions, but interestingly it activates cell survival pathways, downregulates apoptotic mediators and endoplasmic reticulum stress, and restores insulin secretion in response to glucose when beta-cells are cytokine-exposed. These data suggest a potential role of ghrelin in preventing or slowing down the transition from a preclinical to clinically established diabetes by ameliorating the effects of insulitis on beta-cells. PMID- 26257783 TI - Longer-Term Postcure Measurement of Cuspal Deformation Induced by Dimensional Changes in Dental Materials. AB - Aim. This paper presents a simple, versatile in vitro methodology that enables indirect quantification of shrinkage and expansion stresses under clinically relevant conditions without the need for a dedicated instrument. Methods. For shrinkage effects, resulting cusp deformation of aluminum blocks with MOD type cavity, filled with novel filling compositions and commercial cements, has been measured using a bench-top micrometer and a Linear Variable Differential Transformer (LVDT, a displacement transducer) based instrument. Results. The results demonstrated the validity of the proposed simple methodology. The technique was successfully used in longer-term measurements of shrinkage and expansion stress for several dental compositions. Conclusions. In contrast to in situ techniques where a measuring instrument is dedicated to the sample and its data collection, the proposed simple methodology allows for transfer of the samples to the environment of choice for storage and conditioning. The presented technique can be reliably used to quantify stress development of curing materials under clinically relevant (oral) conditions. This enables direct examination and comparison of structural properties corresponding to the final stage of formed networks. The proposed methodology is directly applicable to the study of self curing systems as they require mouth-type conditions (temperature and humidity) to achieve their designed kinetics and reactions. PMID- 26257782 TI - Evaluation of Extraradicular Diffusion of Hydrogen Peroxide during Intracoronal Bleaching Using Different Bleaching Agents. AB - Objectives. Extra radicular diffusion of hydrogen peroxide associated with intracoronal teeth bleaching was evaluated. Methods. 108 intact single rooted extracted mandibular first premolars teeth were selected. The teeth were instrumented with WaveOne system and obturated with gutta percha and divided into four groups (n = 27) according to the bleaching materials used. Each main group was divided into three subgroups (n = 9) according to the time of extra radicular hydrogen peroxide diffusion measurements at 1, 7, and 14 days: group 1 (35% hydrogen peroxide), group 2 (35% carbamide peroxide), group 3 (sodium perborate 30% hydrogen peroxide mixture), and group 4 (sodium perborate-water mixture). Four cemental dentinal defects were prepared just below the CEJ on each root surface. The amount of hydrogen peroxide that leached out was evaluated after 1, 7, and 14 days by spectrophotometer analysis. The results were analyzed using the ANOVA and Tukey's test. Results. Group 1 showed highest extra radicular diffusion, followed by group 3 and group 2, while group 4 showed the lowest mean extra radicular diffusion. Conclusion. Carbamide peroxide and sodium perborate water mixture are the most suitable bleaching materials used for internal bleaching due to their low extra radicular diffusion of hydrogen peroxide. PMID- 26257784 TI - An Unusual Case: Salmonella UTI and Orchitis in HIV Patient. AB - Salmonellosis is a major cause of gastroenteritis in the United States; however, nontyphoidal strains of Salmonella have also been known to cause urinary tract infections, usually transmitted via the fecal-urethral route. This can lead to critical illness in those patients with immune deficiencies, especially HIV, cancer patients, and those with diabetes mellitus. However, the spread of the infection from the urinary tract to involve the testicles and epididymis is very rare. Here, we present the first documented case of an immune-compromised young male with a urinary tract infection with orchitoepididymitis. PMID- 26257785 TI - Transhepatic Embolization of Congenital Intrahepatic Portosystemic Venous Shunts with Associated Aneurysms. AB - Intrahepatic shunts between the portal and systemic venous systems with associated aneurysms are extremely rare. A middle aged woman presented with hepatic encephalopathy and was found to have two intrahepatic portosystemic venous shunts with associated aneurysms. Diagnosis was made by duplex ultrasound and was confirmed with contrast enhanced MRI. Treatment was performed percutaneously with an Amplatzer vascular plug. PMID- 26257786 TI - First Reported Case of Methicillin-Resistant Staphylococcus aureus Vertebral Osteomyelitis with Multiple Spinal and Paraspinal Abscesses Associated with Acupuncture. AB - Acupuncture is one of the oldest medical procedures in the world and originated in China about 2,000 years ago. Acupuncture is a form of complementary medicine and has gained popularity worldwide in the last few decades. It is mainly used for the treatment of chronic pain. Acupuncture is usually considered a safe procedure but has been reported to cause serious complications including death. It has been associated with transmission of many viruses and bacteria. Two cases of Methicillin-Resistant Staphylococcus aureus have been reported recently following acupuncture therapy. We are reporting a case of a 57-year-old Korean female who developed vertebral osteomyelitis and intraspinal and paraspinal abscesses as a complication of acupuncture. Blood cultures, skin lesion culture, and body fluid culture yielded Methicillin-Resistant Staphylococcus aureus (MRSA). Good anatomical and medical knowledge, good hygiene standards, and proper acupuncture techniques should be followed to prevent the complications. Acupuncturists should consistently review the infection control guidelines to acupuncture. This case should raise awareness of such condition and hazards of presumably benign procedures such as acupuncture. PMID- 26257787 TI - Lemierre's Syndrome: A Neglected Disease with Classical Features. AB - We report the case of a previously healthy, immunocompetent 23-year-old male who presented to the Emergency Department with general malaise, difficulty in breathing, fever, and chest pain. He reported a two-week history of progressively worsening sore throat that he presumed to be a viral infection and thus initially neglected. However, when his condition deteriorated, he was admitted to hospital acutely unwell and in respiratory distress. He quickly developed septic shock requiring intensive care admission for inotropic support. Ultrasound and CT imaging revealed internal jugular vein thrombosis with associated septic emboli reaching the lungs to form bilateral cavitations and consequently pleural effusions. Blood cultures were positive for Fusobacterium necrophorum. Based on these findings, a diagnosis of Lemierre's syndrome was made. The patient was treated with appropriate antibiotics and anticoagulation and gradually recovered. He was discharged 20 days after admission with advice to complete a six-week course of antibiotics. PMID- 26257788 TI - Effect of Increasing Doses of gamma-Radiation on Bone Marrow Stromal Cells Grown on Smooth and Rough Titanium Surfaces. AB - Radiation therapy for oral and maxillofacial tumors could damage bone marrow stromal cells (BMSCs) in jaw, which caused dental implant failure. However, how radiation affects BMSCs on SLA (sandblasted with large-grits, acid-etched) surfaces is still unknown. The aim of this study was to investigate effect of different dose of gamma-radiation on BMSCs on SLA and PT (polished titanium) surfaces. Rat BMSCs were radiated with 2, 4, and 8 Gy gamma-radiation and then seeded on both surfaces. Cell adhesion, spreading, and proliferation were tested. The osteogenesis and the adipogenesis ability were examined by Alizarin-Red and Oil-Red staining, respectively. Real-time PCR was performed to detect osteogenic (osteocalcin, OCN; runt-related transcription factor 2, Runx2) and adipogenic (peroxisome proliferator-activated receptor gamma, PPARgamma) gene expression at days 7 and 14 postirradiation. Results showed that gamma-radiation reduced cell proliferation, adhesion, spreading, and osteogenic differentiation. 2 Gy radiation promoted adipogenic differentiation, but it was significantly decreased when dosage reached 4 Gy. In conclusion, results suggest that gamma-radiation influenced BMSCs behaviors in a dosage-dependent manner except adipogenic differentiation, low dose promoted it, and high dose inhibited it. This effect was influenced by surface characteristics, which may explain the different failure rate of various implants in patients after radiation. PMID- 26257789 TI - Platelet-Derived Growth Factor Receptor Alpha as a Marker of Mesenchymal Stem Cells in Development and Stem Cell Biology. AB - Three decades on, the mesenchymal stem cells (MSCs) have been intensively researched on the bench top and used clinically. However, ambiguity still exists in regard to their anatomical locations, identities, functions, and extent of their differentiative abilities. One of the major impediments in the quest of the MSC research has been lack of appropriate in vivo markers. In recent years, this obstacle has been resolved to some degree as PDGFRalpha emerges as an important mesenchymal stem cell marker. Accumulating lines of evidence are showing that the PDGFRalpha (+) cells reside in the perivascular locations of many adult interstitium and fulfil the classic concepts of MSCs in vitro and in vivo. PDGFRalpha has long been recognised for its roles in the mesoderm formation and connective tissue development during the embryogenesis. Current review describes the lines of evidence regarding the role of PDGFRalpha in morphogenesis and differentiation and its implications for MSC biology. PMID- 26257790 TI - Alterations in the Secretome of Clinically Relevant Preparations of Adipose Derived Mesenchymal Stem Cells Cocultured with Hyaluronan. AB - Osteoarthritis (OA) can be a debilitating degenerative disease and is the most common form of arthritic disease. There is a general consensus that current nonsurgical therapies are insufficient for younger OA sufferers who are not candidates for knee arthroplasties. Adipose-derived mesenchymal stem cells (MSCs) therapy for the treatment of OA can slow disease progression and lead to neocartilage formation. The mechanism of action is secretion driven. Current clinical preparations from adipose tissue for the treatment of OA include autologous stromal vascular fraction (SVF), SVF plus mature adipocytes, and culture-purified MSCs. Herein we have combined these human adipose-derived preparations with Hyaluronan (Hylan G-F 20: Synvisc) in vitro and measured alterations in cytokine profile. SVF plus mature adipocytes showed the greatest decreased in the proinflammatory cytokines IL-1beta, IFN-gamma, and VEGF. MCP-1 and MIP-1alpha decreased substantially in the SVF preparations but not the purified MSCs. The purified MSC preparation was the only one to show increase in MIF. Overall the SVF plus mature adipocytes preparation may be most suited of all the preparations for combination with HA for the treatment of OA, based on the alterations of heavily implicated cytokines in OA disease progression. This will require further validation using in vivo models. PMID- 26257792 TI - Perceptions about Eclampsia, Birth Preparedness, and Complications Readiness among Antenatal Clients Attending a Specialist Hospital in Kano, Nigeria. AB - Background. Eclampsia is a reliable indicator of poor birth preparedness and complications readiness. We determined perceptions about eclampsia, birth preparedness, and complications readiness among antenatal clients in Kano, Nigeria. Materials and Method. A cross-sectional design was used to study 250 randomly selected antenatal clients. Data was analyzed using SPSS 16.0. Result. The mean age of the respondents was 26.1 +/- 6.4 years. The majority perceived that eclampsia is preventable through good ANC (76.4%) and hospital delivery (70.8%). Overall, 66.8% had good perception about eclampsia. Having at least secondary school education and multigravidity were associated with good perception about eclampsia on multivariate analysis. About a third (39.6%) of the mothers was less prepared. On binary logistic regression, good perception about eclampsia and multigravidity were associated with being very prepared for birth. Up to 37.6% were not ready for complications. Half (50.4%) knew at least three danger signs of pregnancy, and 30.0% donated blood or identified suitable blood donor. On multivariate analysis, having at least secondary school education, being very prepared for birth, and multigravidity emerged as the only predictors of the respondents' readiness for complications. Conclusion and Recommendations. Health workers should emphasize the practicability of birth preparedness and complications readiness during ANC and in the communities, routinely review plans, and support clients meet-up challenging areas. The importance of girl child education to at least secondary school should be buttressed. PMID- 26257791 TI - Mesenchymal Stromal Cells Affect Disease Outcomes via Macrophage Polarization. AB - Mesenchymal stromal cells (MSCs) are multipotent and self-renewable cells that reside in almost all postnatal tissues. In recent years, many studies have reported the effect of MSCs on the innate and adaptive immune systems. MSCs regulate the proliferation, activation, and effector function of T lymphocytes, professional antigen presenting cells (dendritic cells, macrophages, and B lymphocytes), and NK cells via direct cell-to-cell contact or production of soluble factors including indoleamine 2,3-dioxygenase, prostaglandin E2, tumor necrosis factor-alpha stimulated gene/protein 6, nitric oxide, and IL-10. MSCs are also able to reprogram macrophages from a proinflammatory M1 phenotype toward an anti-inflammatory M2 phenotype capable of regulating immune response. Because of their capacity for differentiation and immunomodulation, MSCs have been used in many preclinical and clinical studies as possible new therapeutic agents for the treatment of autoimmune, degenerative, and inflammatory diseases. In this review, we discuss the central role of MSCs in macrophage polarization and outcomes of diseases such as wound healing, brain/spinal cord injuries, and diseases of heart, lung, and kidney in animal models. PMID- 26257794 TI - The effect of group psycho-education program on the burden of family caregivers with multiple sclerosis patients in Isfahan in 2013-2014. AB - BACKGROUND: Lack of adequate training and support of primary caregivers of multiple sclerosis (MS) patients is the major factor in causing stress, anxiety, and increase of burden. Therefore, the treatment team members such as psychiatric nurses can help these vulnerable people overcome psychiatric pressures effectively not only through their care and referral role but also through their supportive characteristic, which helps the patients improve their clinical status, together with their social, familial, and work adaptation. Therefore, the researcher tried to identify the effect of a group psycho-education program on the burden family caregivers with MS patients. MATERIALS AND METHODS: This is a two-group three-stage clinical trial. The researcher referred to the heads of neurology clinics to present the purpose of the study and to start the sampling. The neurology clinics of AL Zahra University Hospital, and also a Private Neurology Clinic were selected to collect the data of the study. The subjects were randomly selected, and then, assigned to two groups of study and control. RESULTS: Independent t-test showed a significant reduction in family caregivers' burden immediately after and 1-month after intervention in the study group, compared to control. Repeated measure ANOVA showed a significant reduction in caregivers' burden mean score in the study group (P < 0.001). CONCLUSIONS: As group psycho-education reduced family caregivers' burden, it is recommended to develop and design other programs for the family caregivers of the patients with MS. PMID- 26257793 TI - Challenges associated with the implementation of the nursing process: A systematic review. AB - BACKGROUND: Nursing process is a scientific approach in the provision of qualified nursing cares. However, in practice, the implementation of this process is faced with numerous challenges. With the knowledge of the challenges associated with the implementation of the nursing process, the nursing processes can be developed appropriately. Due to the lack of comprehensive information on this subject, the current study was carried out to assess the key challenges associated with the implementation of the nursing process. MATERIALS AND METHODS: To achieve and review related studies on this field, databases of Iran medix, SID, Magiran, PUBMED, Google scholar, and Proquest were assessed using the main keywords of nursing process and nursing process systematic review. The articles were retrieved in three steps including searching by keywords, review of the proceedings based on inclusion criteria, and final retrieval and assessment of available full texts. RESULTS: Systematic assessment of the articles showed different challenges in implementation of the nursing process. Intangible understanding of the concept of nursing process, different views of the process, lack of knowledge and awareness among nurses related to the execution of process, supports of managing systems, and problems related to recording the nursing process were the main challenges that were extracted from review of literature. CONCLUSIONS: On systematically reviewing the literature, intangible understanding of the concept of nursing process has been identified as the main challenge in nursing process. To achieve the best strategy to minimize the challenge, in addition to preparing facilitators for implementation of nursing process, intangible understanding of the concept of nursing process, different views of the process, and forming teams of experts in nursing education are recommended for internalizing the nursing process among nurses. PMID- 26257795 TI - Evaluating different types of malpractices in midwifery that were referred to the forensic medicine commission and the medical council between 2006 and 2011 in Isfahan province, 2013. AB - BACKGROUND: Medical malpractices in obstetrics are one of the main health concerns since in addition to the mortalities and morbidities caused for the two susceptible groups of mothers and neonates, they may lead to difficulties for the accused gynecologists and midwives in returning to their routine medical career and giving services to the patients. Hence, this study was conducted to evaluate different types of malpractices in midwifery that were referred to the legal medical commission and medical council in Isfahan province. MATERIALS AND METHODS: In this cross-sectional descriptive study, we evaluated the data from all midwifery cases referred to the forensic medicine commission and medical council in Isfahan province between 2006 and 2011, with at least one lawsuit confirmed by the jury. RESULTS: The results showed that in a total of 206 investigated cases at the medical council and forensic medicine commission in Isfahan, 66 cases of medical error sentences including 38 cases in medical council and 28 cases in forensic medicine commission were proved, which revealed 32% of malpractice in midwifery services in 2006-2011 in Isfahan. Negligence (39.2%), imprudence (23.5%), and disobedience of governmental regulations (19.6%) stood among the most commonly reported malpractices. Our findings also suggest that the most common malpractices happened in the postpartum period with a frequency of 44.7%; in addition, governmental hospitals were shown to have the most frequent malpractices with a frequency of 50%. CONCLUSIONS: Our results reveal that malpractices in midwifery services during and after delivery are so common, leading to irreversible complications to the mothers' and neonates' health in the society. On the other hand, considering the fact that most of these malpractices are preventable, related education, pertinent plans, and proper supervision sys. PMID- 26257796 TI - The effect of resistance exercise on mean blood pressure in the patients referring to cardiovascular research centre. AB - BACKGROUND: One of the most important risk factors for cardiovascular disease is hypertension. 1 billion people in the world and 25-35% of the adult population in Iran suffer from hypertension. Despite the emphasis on medicational treatments, non-medicational treatments and modification of lifestyle, including physical activity and exercise, are important for the control and treatment of hypertension and lead to a reduction in cardiovascular diseases. Among the various types of exercises, resistance exercise has been considered important by the cardiologists. The present study investigates the effect of resistance exercise on mean blood pressure in the cardiovascular patients. MATERIALS AND METHODS: In a randomized clinical trial, 40 patients admitted to the rehabilitation unit of cardiovascular research center were assigned to study and control groups. Demographic data were collected. Their blood pressure values were measured and recorded once 1 day before the beginning of the intervention and another time 1 day after its completion. All study subjects participated in two 45-60 min exercise sessions for eight straight weeks. The control group followed routine rehabilitation unit protocol that was aerobic exercise. The study group subjects performed resistance exercise in addition to routine exercise. The weight was determined in the first session of the intervention. At the beginning, the number of the repetitions in the range of motion was 10, which was increased gradually to 15. After it reached 15 repetitions, the amount of weight was increased by 3-5% and the number of sets increased. RESULTS: One day before the beginning of the intervention, mean systolic blood pressure was 128.21 (15.39) mmHg in the study group and 120.00 (20.51) mmHg in the control group. Mean diastolic blood pressure was 82.50 (9.35) mmHg in the study group and 82.00 (13.11) mmHg in the control group. There were no differences between the groups in terms of mean systolic and diastolic blood pressure (P > 0.05). After the end of the intervention, mean systolic blood pressure values were 116.42 (7.18) mmHg and 112.00 (12.60) mmHg in the study and control groups, respectively. There were no significant differences between the groups (P = 0.24). Mean diastolic blood pressure values were 81.78 (7.99) mmHg in the study group and 78.25 (12.48) mmHg in the control group. There was no significant difference between the groups (P = 0.35). At the end of the intervention, mean systolic blood pressure in the study group decreased significantly (P = 0.02). CONCLUSIONS: In the present study, the effect of resistance exercise on mean systolic blood pressure showed a significant difference, caused by the aerobic exercise. PMID- 26257797 TI - Motivating factors among Iranian nurses. AB - BACKGROUND: One of the most important challenges of Iranian health care system is "quality of care," and it is assumed that motivated nurses are more ready to provide better care. There are limited studies investigating Iranian nurses' motivations; however, factors which motivate them have not been studied yet. Identifying the motivating factors enables nurse managers to inspire nurses for continuous quality improvement. The aim of this study was to identify motivating factors for Iranian hospital nurses. MATERIALS AND METHODS: This is a cross sectional descriptive study in which 310 nurses working at 14 hospitals of Tehran University of Medical Sciences were selected by proportionate stratified random sampling. Data were collected in 2010 by a researcher-developed questionnaire. Descriptive statistics and independent t-test, analysis of variance, Tukey post hoc test, Chi-Square and Fisher's exact test were used for statistical analysis by Statistical Package for Social Sciences (SPSS) version 16. RESULTS: The mean score of motivation was 90.53 +/- 10.76 (range: 59-121). Four motivating factors including "career development" (22.63 +/- 5.66), "job characteristics" (34.29 +/- 4), "job authority" (18.48 +/- 2.79), and "recognition" (15.12 +/- 2.5) were recognized. The least mean of the motivation score, considering the number of items, was 3.23 for career development, while the highest mean was 3.81 for job characteristics. CONCLUSIONS: The findings showed that motivation of nurses was at a medium level, which calls for improvement. The factors that have the greatest potential to motivate nurses were identified in this study and they can help managers to achieve the goal of continuous quality improvement. PMID- 26257798 TI - The effects of discharge training and counseling on post-discharge problems in patients undergoing coronary artery bypass graft surgery. AB - BACKGROUND: Advances in coronary artery surgery have reduced morbidity, mortality, and rates of graft occlusion. Discharge programs are important services for the continuity of treatment and must encompass physical, psychological, and social aspects of individual patient care. This study aimed at investigating the effect of planned discharge training and counseling on the problems experienced by patients undergoing coronary artery bypass graft (CABG) surgery. MATERIALS AND METHODS: A semi-experimental study was performed on 100 patients undergoing CABG surgery in the surgery department. During a period of 9 months from January to September 2013, the patients in the intervention group were provided with adequate discharge training and counseling with a booklet before surgery and counseling until 6 weeks after discharge, while the control group patients received only routine clinical procedures, i.e. prescribing medicine, controlling vital signs, and wound dressing. The data were analyzed using Statistical Package for the Social Sciences (SPSS) 23. Frequency and distribution were used to describe the data, and paired sample t-test, variance analysis, Fisher's exact test, and Chi-squared tests were also used. RESULTS: The reported problems for both groups had a descending pattern during the three follow-ups. However, this pattern had a greater slope in the intervention group compared to the control one. As a result of these education programs, problems were fewer in the intervention group than in the control group (P < 0.05). CONCLUSIONS: Discharge training and counseling given to the intervention group had a positive impact on decreasing the problems that the patients had. Therefore, the institutions may be recommended to support multidisciplinary patient training and counseling activities using the methods described in this study. PMID- 26257799 TI - Comparison of indomethacin suppository and lidocaine cream on post-episiotomy pain: A randomized trial. AB - BACKGROUND: One of the most important problems after episiotomy is perineal pain which is more severe on the first day of postpartum period. The aim of this study was to compare the analgesic effects of indomethacin suppository and lidocaine cream in the management of post-episiotomy pain. MATERIALS AND METHODS: In a randomized, controlled trial, 60 primiparous women who had mediolateral episiotomy received 50 mg indomethacin suppository (n = 30) or 2% lidocaine cream (n = 30) in the postpartum period in Hajar Hospital in Shahrekord (Iran). The mean severity of post-episiotomy pain was assessed with the first complaint and at 6, 12, and 24 h after the delivery, and compared in the two groups. The visual analog scale (VAS) was used for pain recording and data were analyzed with independent-samples t-test, chi(2), and Fisher's exact tests, and significance was defined as P < 0.05. RESULTS: With the first complaint of pain, the mean intensity of pain was 4.9 (1.9) in the indomethacin group and 4.9 (1.8) in the lidocaine group, and the difference was not significant (P = 0.25). Six hours after birth, it was 3.3 (1.3) in the indomethacin group and 3.2 (1.9) in the lidocaine group, and there was not a significant difference between the two groups (P = 0.90). No significant difference was found between the two groups at 12 h after birth [2.3 (1.7) vs 2.5 (1.7); P = 0.59]. Also, the difference was not significant at 24 h after birth [1.5 (1.3) vs 1.8 (1.3); P = 0.31]. CONCLUSIONS: It was concluded from the study that indomethacin suppository and lidocaine cream have similar efficacy on episiotomy pain relief on the first day of postpartum period. PMID- 26257800 TI - Depression and anxiety in pregnancy and postpartum in women with mild and severe preeclampsia. AB - BACKGROUND: Risk for anxiety and depression is increased in women with high-risk pregnancy. The aim of this study was to evaluate anxiety and depression in women with mild and severe preeclampsia at admission and 6 weeks postpartum. MATERIALS AND METHODS: In this cohort study, 122 preeclamptic women who were admitted to the Public hospital and Tamin Ejtemaee hospital of Mashhad were included. Selection was done by convenience sampling method. Beck Depression Inventory II (BDI-II) and Spielberger State-Trait Anxiety Inventory (STAI) were completed at admission and 6 weeks after delivery. Data were analyzed by SPSS 16 using Chi square, Fisher's exact test, Mann-Whitney U test, and Repeated measurement. RESULTS: The mean depression score was 4.81 +/- 4.09 at admission and 11.17 +/- 5.5 at 6 weeks postpartum. The mean of trait anxiety was 42.5 +/- 10.5 at admission and 32.3 +/- 6.5 at 6 weeks postpartum, and the mean of state anxiety score at admission was 43.09 +/- 9.5 and at 6 weeks postpartum was 31.99 +/- 5.9. There was a significant difference between the scores of depression (F = 3.8, P < 0.001), state anxiety (F = 1.52, P < 0.001), and trait anxiety (F = 1.5, P < 0.001) at admission and 6 weeks postpartum. No significant differences were found between severity of preeclampsia and the scores of depression, state anxiety, and trait anxiety at admission and 6 weeks postpartum. CONCLUSIONS: The mean score of state and trait anxiety decreased significantly in preeclamptic women from admission to 6 weeks postpartum, but the mean score of depression increased. Severity of preeclampsia was not an independent risk factor of depression and anxiety. PMID- 26257801 TI - The effect of Rosmarinus herbal tea on occupational burnout in Iran Chemical Industry Investment company employees. AB - BACKGROUND: Burnout is one of the most important problems that the employees encounter. Many health problems arise due to burnout which is to be dealt with by the employees and the owners in the industry. Among many different ways of dealing with this problem, herbal therapy seems to be a promising solution. The present study intended to investigate the effect of Rosmarinus officinalis (RO) on burnout in employees who work in industrial environments. MATERIALS AND METHODS: An experimental study was performed to see whether RO has an effect on burnout or not. A total of 66 employees, aged between 20 and 60 years, who had worked for at least 1 year in the technical wards of Iran Chemical Industry Investment Company took part in the study. The participants were randomly assigned to two groups of control (n = 33) and RO (n = 33). The RO group received 4 g of Rosemary in 150 cc water per day for 2 months. The control group, on the other hand, did not receive anything. The data were collected via Geldard (1989) Burnout Inventory before and after the treatment. A t-test was performed to analyze the collected data. RESULTS: The results of statistical tests showed that after intervention, the score of occupational burnout in RO group was better, and a significant difference was found between the control and experimental groups (P = 0.03), in favor of the experimental group. CONCLUSIONS: The results of the study revealed that Rosmarinus had a positive effect on burnout in employees in this study. Further studies in this field are suggested. PMID- 26257802 TI - Social support: An approach to maintaining the health of women who have experienced stillbirth. AB - BACKGROUND: Stillbirth is one of the deepest losses that can inflict a broad range of cognitive, mental, spiritual, and physical turmoil. Many researchers believe that the failure to provide the care required by health teams during the hard times is the main determinant of maternal mental health in the future. In other words, social support can significantly improve the mental health outcomes of mothers after stillbirth. This study aimed to explore social support to aid mothers in adaptation after the experience of stillbirth. MATERIALS AND METHODS: This was a qualitative content analysis in which 15 women who had experienced stillbirth participated. They were selected through purposeful sampling method. Data were gathered by individual interviews recorded on audiotapes, transcribed, and analyzed. Interview transcriptions were coded and then classified. Finally, two main categories and five subcategories emerged. RESULTS: Analysis of participants' viewpoints and their statements about social support led to the emergence of the two main categories of support from relatives and support from social support systems with two and three subcategories, respectively. Analysis of findings showed that mothers experiencing stillbirth need the support of their spouse and family and friends through sympathizing, in performing everyday activities and to escape loneliness. These women require support from a peer group to exchange experiences and from trauma counseling centers to meet their needs. CONCLUSIONS: It seems necessary to revise and modify the care plan in the experience of stillbirth using these results and, of course, to be considered by a panel of experts in order to provide social support to these women. Thus, midwives and healthcare provider can act, based on the development and strengthening of social protection of women experiencing stillbirth, to provide these women with effective and appropriate care. PMID- 26257803 TI - Comparing the estimation of postpartum hemorrhage using the weighting method and National Guideline with the postpartum hemorrhage estimation by midwives. AB - INTRODUCTION: In developing countries, hemorrhage accounts for 30% of the maternal deaths. Postpartum hemorrhage has been defined as blood loss of around 500 ml or more, after completing the third phase of labor. Most cases of postpartum hemorrhage occur during the first hour after birth. The most common reason for bleeding in the early hours after childbirth is uterine atony. Bleeding during delivery is usually a visual estimate that is measured by the midwife. It has a high error rate. However, studies have shown that the use of a standard can improve the estimation. The aim of the research is to compare the estimation of postpartum hemorrhage using the weighting method and the National Guideline for postpartum hemorrhage estimation. MATERIALS AND METHODS: This descriptive study was conducted on 112 females in the Omolbanin Maternity Department of Mashhad, for a six-month period, from November 2012 to May 2013. The accessible method was used for sampling. The data collection tools were case selection, observation and interview forms. For postpartum hemorrhage estimation, after the third section of labor was complete, the quantity of bleeding was estimated in the first and second hours after delivery, by the midwife in charge, using the National Guideline for vaginal delivery, provided by the Maternal Health Office. Also, after visual estimation by using the National Guideline, the sheets under parturient in first and second hours after delivery were exchanged and weighted. The data were analyzed using descriptive statistics and the t-test. RESULTS: According to the results, a significant difference was found between the estimated blood loss based on the weighting methods and that using the National Guideline (weighting method 62.68 +/- 16.858 cc vs. National Guideline 45.31 +/- 13.484 cc in the first hour after delivery) (P = 0.000) and (weighting method 41.26 +/- 10.518 vs. National Guideline 30.24 +/- 8.439 in second hour after delivery) (P = 0.000). CONCLUSIONS: Natural child birth education by using the National Guideline can increase the accuracy of estimated blood loss. Therefore, training the personnel to use this guideline is recommended. However, It has less accuracy than 'sheet weighing'. Consequently, usage of symptoms and the weighing method is recommended in cases of postpartum bleeding. PMID- 26257804 TI - Resources-tasks imbalance: Experiences of nurses from factors influencing workload to increase. AB - BACKGROUND: While nursing workload is a worldwide challenge, less attention has been given to the determining factors. Understanding these factors is important and could help nursing managers to provide suitable working environment and to manage the adverse outcomes of nursing workload. The aim of this study was to discover nurses' experiences of determinant factors of their workload. MATERIALS AND METHODS: In this qualitative study, the participants included 15 nurses working in two hospitals in Tehran, Iran. The data were collected through 26 unstructured interviews and were analyzed using conventional content analysis. The rigor has been guaranteed with prolonged engagement, maximum variance sampling, member check, and audit trail. RESULTS: Resource-task imbalance was the main theme of nurses' experiences. It means that there was an imbalance between necessary elements to meet patients' needs in comparison with expectation and responsibility. Resource-task imbalance included lack of resource, assignment without preparation, assigning non-care tasks, and patients' and families' needs/expectations. CONCLUSIONS: A deep and comprehensive imbalance between recourses and tasks and expectations has been perceived by the participants to be the main source of work overload. Paying more attention to resource allocation, education of quality workforce, and job description by managers is necessary. PMID- 26257805 TI - Asymmetric dimethylarginine (ADMA), nitric oxide metabolite, and estradiol levels in serum and peritoneal fluid in women with endometriosis. AB - BACKGROUND: Increase in nitric oxide (NO) concentration accompanied by alteration in peritoneal immune defense reactions is involved in the pathogenesis of endometriosis. Asymmetric dimethylarginine is an endogenous competitive inhibitor of NO synthase. This study was designed to compare NO metabolite (nitrite), asymmetric dimethylarginine, and estradiol concentrations in serum and peritoneal fluid (PF) of patients with and without endometriosis. MATERIALS AND METHODS: Subjects were assigned to two groups based on their laparoscopic results. The groups consisted of women with and without endometriosis (90 and 89 participants, respectively). The serum and peritoneal levels of nitrite (stable NO metabolite), asymmetric dimethylarginine, and estradiol were measured using enzyme-linked immunosorbent assay (ELISA) kits. These parameters were analyzed and compared between the groups statistically using SPSS software version 16. RESULTS: Both nitrite and asymmetric dimethylarginine levels were significantly higher in the serum of the participants from both groups than those in the PF group (P < 0.05). However, no significant difference in the asymmetric dimethylarginine level was detected between the two groups. In addition, the PF level of nitrite increased significantly in patients with endometriosis when compared with non-endometriosis subjects (P < 0.05). The PF levels of estradiol in both groups were significantly higher than the serum levels of estradiol (P < 0.05). CONCLUSIONS: The NO metabolite level of PF implies the possible role of NO in the pathogenesis of endometriosis. PMID- 26257806 TI - A survey of nurses' awareness of patient safety culture in neonatal intensive care units. AB - BACKGROUND: Patient safety is considered as the most important quality for healthcare. One of the main factors that play an important role in the promotion of healthcare institutes is patient safety. This study describes the nurses' awareness of patient safety culture in neonatal intensive care units (NICUs). MATERIALS AND METHODS: In this descriptive study, 83 nurses working in neonatal intensive care units of hospitals affiliated to Isfahan University of Medical Sciences, Iran, were selected using purposive sampling. Data collection tools consisted of the demographic characteristics questionnaire and the Hospital Survey on Patient Safety Culture. Data were analyzed by using SPSS software. RESULTS: The dimension that received the highest positive response rate was "expectations and actions of the supervisor/manager in promoting safety culture." The dimension with the lowest percentage of positive responses was "frequency of error reporting." 21.70% of the NICU nurses reported one or two incidents in their work units in the previous 12 months. CONCLUSIONS: In order to create and promote patient safety, appropriate management of resources and a correct understanding of patient safety culture are required. In this way, awareness of dimensions which are not acceptable provides the basic information necessary for improving patient safety. PMID- 26257807 TI - The effect of saline lock on phlebitis rates of patients in cardiac care units. AB - BACKGROUND: Despite advances in the field of intravenous therapy, phlebitis is still a common complication of peripheral venous catheter and finding an appropriate solution to prevent and reduce the incidence of this complication remains challenging. One of the methods used in reducing the incidence of phlebitis is the use of saline lock, which is forgotten in most hospitals. Therefore, this study aimed to evaluate its impact on the incidence and severity of phlebitis. MATERIALS AND METHODS: In a single-blind (the researcher) clinical trial, 88 patients with peripheral venous catheter admitted in cardiac care units in selected hospitals of Isfahan University of Medical Sciences, Iran, were selected through convenient sampling method. They were randomly divided into two groups of intervention and control groups using random number table. The intervention group received 3 ml of 0.9% normal saline sterilized before and after each intravenous drug or every 12 h. However, in the control group, the intravenous drugs were given as routine and saline lock was not used. The evaluation of intravenous catheter regarding the incidence of phlebitis and its degrees using Jackson's Visual Infusion Phlebitis Scale was performed 6 times within 72 h (every 12 h). Results were evaluated by SPSS software using descriptive statistics, Chi-square test, t-test, and Mann-Whitney test. RESULTS: Results showed that there was a statistically significant difference between the two groups regarding the degree of phlebitis (P = 0.003). The percentage of phlebitis incidence in the control group was 88.6% and in the intervention group was 43.2%. There was a statistically significant difference between the two groups (P < 0.001). The risk of incidence of phlebitis in the group without saline lock (control), compared to the intervention group, was 10.3 times greater (CI = 95%). The incidence of phlebitis in both groups increased with increase in the duration of catheter placement. CONCLUSIONS: The results of this study showed that the use of saline lock in the intervention group compared to the control group, in which saline lock was not used, can have a significant impact on reducing the incidence of phlebitis and its degree. PMID- 26257808 TI - Effects of pain management program on the length of stay of patients with decreased level of consciousness: A clinical trial. AB - BACKGROUND: Critical care patients are at higher risk for untreated pain. Pain has persistent and untreated effects on most of the body systems and results in development of complications, chronic pain, and increased length of stay. The aim of this study was to determine the effects of the implementation of a pain management program on the length of stay in patients with decreased level of consciousness, admitted in Al-Zahra hospital intensive care units (ICUs) in 2013. MATERIALS AND METHODS: In this clinical trial, 50 subjects with decreased level of consciousness were selected by convenient sampling from the ICU wards of Al Zahra hospital, Isfahan, Iran and were randomly assigned to two groups of study and control. Pain management program was applied on the study group and routine care was implemented in the control group. Data including demographic data and length of stay of patients in the ICUs were collected and analyzed using descriptive statistics and Chi-square test, independent t-test, and paired t test. RESULTS: Results showed that out of 50 subjects attending the study, there were 40% female and 60% male subjects in study, and 52% female and 48% male subjects in control group. (P = 0.395). Overall mean length of stay of the patients in the ICUs was significantly lower in the case group [3.2 (1.4)] days compared to the control group [7.4 (4.8) days] (P < 0.001). CONCLUSIONS: This study showed that overall mean length of stay of patients in the ICUs was significantly lower in the study group compared to the control group. It is suggested to use this program for patients in ICUs with decreased level of consciousness after a general surgery. PMID- 26257809 TI - The effect of massage therapy on occupational stress of Intensive Care Unit nurses. AB - BACKGROUND: One of the main causes of stress in the lives of people is their jobs. Occupational stress is causing a wide range of significant issues in health and community services. Nursing is the most stressful profession in the health services. Massage therapy is one way of coping with stress. This study was conducted to determine the effect of massage therapy on stress in nurses. MATERIALS AND METHODS: This study was a clinical trial on 66 male and female nurses working in intensive care units (dialysis, ICU, and CCU) of Isfahan University of Medical Sciences, Iran, in 2013. Participants were selected according to the aims and inclusion criteria of the study. Then, they were randomly divided into experimental and control groups. The Occupational Stress Inventory (OSI) (Osipow and Spokane, 1987) was completed by participants of the two groups before, immediately after, and 2 weeks after the intervention. General Swedish massage was performed on participants of the experimental group for 25 min in each session, twice a week for 4 weeks. Data were analyzed by descriptive and inferential statistics [Chi-square, t-test, and repeated measures analysis of variance (ANOVA)] using SPSS software. RESULTS: Results showed that the difference in overall mean occupation stress scores between experimental and control groups 2 weeks after the intervention was significant (P < 0.001). CONCLUSIONS: According to the results, it is recommended that massage, as a valuable noninvasive method, be used for nurses in intensive care units to reduce their stress, promote mental health, and prevent the decrease in quality of nursing work life. PMID- 26257810 TI - Relationship of sexual dysfunction and its associated factors in women with genital and breast cancers. AB - BACKGROUND: Sexuality is a basic and important factor in human experiences, which varies among different types of cancers. This study was carried out with the aim of defining the relationship between sexual dysfunction and related factors in genital and breast cancers. MATERIALS AND METHODS: This cross-sectional study was conducted on 150 women with genital and breast cancers admitted to two specialized hospitals in Isfahan and by using a two-stage sampling method. Participants completed demographic/disease questionnaire and sexual function questionnaire. Collected data were analyzed by using SPSS software version 14 and statistical tests of correlation coefficient, Student's t-test and one-way analysis of variance (ANOVA). RESULTS: The obtained results showed that 47% of women had sexual dysfunction with the mean (SD) age of 47 (7.7) years (with the range of 25-65 years). There was a significant correlation between sexual functioning and age, occupation, educational level, and treatment duration (P < 0.05). There was also a significant correlation between the stage of disease, primary disorder (0.003), and recent disorder (0.028). Meanwhile, Chi-square test showed no significant relationship between cancer type and primary disorder (0.403) and recent disorder (0.416). CONCLUSIONS: Breast and genital cancers may result in significant difficulties with sexual functioning and sexual life. Addressing these problems is essential to improve the quality of life in women with cancer and further investigations should be conducted for prevention and treatment of disorders by the health authorities. PMID- 26257811 TI - An assessment of the stressors and ways of coping in Iranian medical sciences students. AB - BACKGROUND: Several studies have reported that medical sciences students are usually dealing with severe stress. However, no study is available on ways of coping in medical sciences students in Iran. As socio-cultural factors may affect the students' responses toward stress, this study aimed to investigate the stressors and ways of coping among students of Guilan University of Medical Sciences (GUMS). MATERIALS AND METHODS: A cross-sectional study was conducted on 487 randomly selected students in GUMS in 2012. The student stress scale and Lazarus ways of coping scale were used for data collection. Descriptive statistics were calculated. Also, Chi-square and Fisher's exact tests, Kruskal Wallis and Mann-Whitney U tests, and logistic regression analysis were utilized for data analysis. cross-sectional study was conducted on 487 randomly selected students in GUMS in 2012. The student stress scale and Lazarus ways of coping scale were used for data collection. Descriptive statistics were calculated. Also, Chi-square and Fisher's exact tests, Kruskal-Wallis and Mann-Whitney U tests, and logistic regression analysis were utilized for data analysis. RESULTS: In the majority of students (61.4%), interpersonal factors were the dominant stressor. Most of the students used problem-focused ways of coping (79.7%). Chi square test showed a significant relationship between gender and ways of coping (P = 0.03). CONCLUSIONS: Interpersonal sources of stress were the most common stressors among the medical sciences students. Establishing workshops on communication skills and effective counseling system are suggested. PMID- 26257812 TI - Ebola disease: Infection prevention and control in hospital and community settings. PMID- 26257813 TI - Performance of exome sequencing for pharmacogenomics. AB - AIM: We present the potential false-negative rate of exome sequencing for the detection of pharmacogenomic variants. MATERIALS & METHODS: Depth of coverage of 1928 pharmacogenomically relevant variant positions was ascertained from 62 exome sequenced samples. RESULTS: Approximately 14% of the 1928 variant locations examined had inadequate depth of coverage (<20x). The variants with inadequate coverage were predominantly located outside of protein-coding portions and included some clinically relevant variant positions, such as the warfarin VKORC1 variant. CONCLUSION: While the use of exome sequencing is becoming more prevalent in fundamental research, clinical trials and clinical use; there is a possibility of false-negative results. The possible quality issues such as false-negative rate should be considered with the use of exome sequencing. PMID- 26257814 TI - Gene Expression Response of Trichophyton rubrum during Coculture on Keratinocytes Exposed to Antifungal Agents. AB - Trichophyton rubrum is the most common causative agent of dermatomycoses worldwide, causing infection in the stratum corneum, nails, and hair. Despite the high prevalence of these infections, little is known about the molecular mechanisms involved in the fungal-host interaction, particularly during antifungal treatment. The aim of this work was to evaluate the gene expression of T. rubrum cocultured with keratinocytes and treated with the flavonoid trans chalcone and the glycoalkaloid alpha-solanine. Both substances showed a marked antifungal activity against T. rubrum strain CBS (MIC = 1.15 and 17.8 ug/mL, resp.). Cytotoxicity assay against HaCaT cells produced IC50 values of 44.18 to trans-chalcone and 61.60 uM to alpha-solanine. The interaction of keratinocytes with T. rubrum conidia upregulated the expression of genes involved in the glyoxylate cycle, ergosterol synthesis, and genes encoding proteases but downregulated the ABC transporter TruMDR2 gene. However, both antifungals downregulated the ERG1 and ERG11, metalloprotease 4, serine proteinase, and TruMDR2 genes. Furthermore, the trans-chalcone downregulated the genes involved in the glyoxylate pathway, isocitrate lyase, and citrate synthase. Considering the urgent need for more efficient and safer antifungals, these results contribute to a better understanding of fungal-host interactions and to the discovery of new antifungal targets. PMID- 26257815 TI - Antiviral and Antioxidant Activities of Sulfated Galactomannans from Plants of Caatinga Biome. AB - Dengue represents a serious social and economic public health problem; then trying to contribute to improve its control, the objective of this research was to develop phytoterapics for dengue treatment using natural resources from Caatinga biome. Galactomannans isolated from Adenanthera pavonina L., Caesalpinia ferrea Mart., and Dimorphandra gardneriana Tull were chemically sulfated in order to evaluate the antioxidant, and antiviral activities and the role in the inhibition of virus DENV-2 in Vero cells. A positive correlation between the degree of sulfation, antioxidant and antiviral activities was observed. The sulfated galactomannans showed binding to the virus surface, indicating that they interact with DENV-2. The sulfated galactomannans from C. ferrea showed 96% inhibition of replication of DENV-2 followed by D. gardneriana (94%) and A. pavonina (77%) at 25 ug/mL and all sulfated galactomannans also showed antioxidant activity. This work is the first report of the antioxidant and antiviral effects of sulfated galactomannans against DENV-2. The results are very promising and suggest that these sulfated galactomannans from plants of Caatinga biome act in the early step of viral infection. Thus, sulfated galactomannans may act as an entry inhibitor of DENV-2. PMID- 26257816 TI - Strong Manual Acupuncture Manipulation Could Better Inhibit Spike Frequency of the Dorsal Horn Neurons in Rats with Acute Visceral Nociception. AB - Afferent impulses from visceral nociception can be regulated by acupuncture at spinal cord level; however, the effects of different manual acupuncture (MA) manipulations on the afferent impulses are still unknown. Here, we analyzed the spike frequency of excitatory gastric-related wide dynamic range (WDR) neurons in spinal dorsal horn (SDH) following acute gastric distension (GD) in rats and compared their responses to MA manipulations with four different frequencies (0.5, 1, 2, and 3 Hz) at Zusanli (ST36). Results indicated that the spike frequency was increased by acute GD stimulation. Under acute GD circumstances, the spike frequency was further activated by weak MA stimulation (0.5 and 1 Hz), while being significantly inhibited by strong MA stimulation (2 and 3 Hz). After 10 minutes of the strong MA stimulation, same intensity of acute GD caused less spike frequency. Our previous researches had demonstrated that different MA manipulations could increase spike frequency in an intensity-dependent manner in normal rats; these findings suggest that acupuncture may have different modulatory effects depending on the state of the stomach. Since neuronal spike frequency was related to the level of nociception, the results suggest that strong MA manipulation may have better effect on acute visceral nociception. PMID- 26257817 TI - Alternative, Complementary, and Forgotten Remedies for Atopic Dermatitis. AB - Atopic dermatitis, perhaps more than other dermatologic diseases, has garnered much attention in the realm of alternative medicine. This may be because its etiopathogenesis is incompletely understood, it is increasingly common, and it waxes and wanes often without clear precipitants, opening up many opportunities for misinterpretation. Herein we explore the evidence for a number of different alternative and complementary therapies, from textiles to vitamin supplements. By definition, none have enough data to be deemed "effective" in a conventional sense, but it is hopeful that some show promising evidence that may one day lead to mainstream acceptance with further research. PMID- 26257818 TI - Lonicerae Japonicae Flos and Lonicerae Flos: A Systematic Pharmacology Review. AB - Lonicerae japonicae flos, a widely used traditional Chinese medicine (TCM), has been used for several thousand years in China. Chinese Pharmacopeia once included Lonicerae japonicae flos of Caprifoliaceae family and plants of the same species named Lonicerae flos in general in the same group. Chinese Pharmacopeia (2005 Edition) lists Lonicerae japonicae flos and Lonicerae flos under different categories, although they have the similar history of efficacy. In this study, we research ancient books of TCM, 4 main databases of Chinese academic journals, and MEDLINE/PubMed to verify the origins and effects of Lonicerae japonicae flos and Lonicerae flos in traditional medicine and systematically summarized the research data in light of modern pharmacology and toxicology. Our results show that Lonicerae japonicae flos and Lonicerae flos are similar pharmacologically, but they also differ significantly in certain aspects. A comprehensive systematic review and a standard comparative pharmacological study of Lonicerae japonicae flos and Lonicerae flos as well as other species of Lonicerae flos support their clinical safety and application. Our study provides evidence supporting separate listing of Lonicerae japonicae flos and Lonicerae flos in Chinese Pharmacopeia as well as references for revision of relevant pharmacopeial records dealing with traditional efficacy of Lonicerae japonicae flos and Lonicerae flos. PMID- 26257819 TI - Co-delivery of siRNA and therapeutic agents using nanocarriers to overcome cancer resistance. AB - There are two main mechanisms by which cells become multidrug resistant (MDR): by increasing drug efflux pumps on the cell membrane and by increasing anti apoptotic pathways. The use of nanotechnology to develop nanodelivery systems has allowed researchers to overcome limitations of antineoplastic drugs by increasing the solubility of the drug and decreasing the toxicity to healthy tissues. By encapsulating drugs into nanoparticles that bypass the efflux pumps, drug efflux is reduced, hence increasing the intracellular concentration of the drug. siRNA has the ability to disrupt cellular pathways by knocking down genes, opening the door to down regulating anti-apoptotic pathways. The use of nanocarriers to deliver siRNA, prevents both renal clearance and RNase degradation by protecting siRNA chains, increasing their half life in blood. It has been suggested that co delivering drugs and siRNA together in the same delivery system would be more effective in overcoming resistance of cancer cells than co-treatment of cancer cells with delivery systems carrying either siRNA or drugs. In this study we discuss the progress of nanoscale co-delivery systems in overcoming multidrug cancer resistance. PMID- 26257820 TI - A multiobjective approach for identifying protein complexes and studying their association in multiple disorders. AB - BACKGROUND: Detecting protein complexes within protein-protein interaction (PPI) networks is a major step toward the analysis of biological processes and pathways. Identification and characterization of protein complexes in PPI network is an ongoing challenge. Several high-throughput experimental techniques provide substantial number of PPIs which are widely utilized for compiling the PPI network of a species. RESULTS: Here we focus on detecting human protein complexes by developing a multiobjective framework. For this large human PPI network is partitioned into modules which serves as protein complex. For building the objective functions we have utilized topological properties of PPI network and biological properties based on Gene Ontology semantic similarity. The proposed method is compared with that of some state-of-the-art algorithms in the context of different performance metrics. For the purpose of biological validation of our predicted complexes we have also employed a Gene Ontology and pathway based analysis here. Additionally, we have performed an analysis to associate resulting protein complexes with 22 key disease classes. Two bipartite networks are created to clearly visualize the association of identified protein complexes with the disorder classes. CONCLUSIONS: Here, we present the task of identifying protein complexes as a multiobjective optimization problem. Identified protein complexes are found to be associated with several disorders classes like 'Cancer', 'Endocrine' and 'Multiple'. This analysis uncovers some new relationships between disorders and predicted complexes that may take a potential role in the prediction of multi target drugs. PMID- 26257821 TI - Orchestration of Morphogenesis in Filamentous Fungi: Conserved Roles for Ras Signaling Networks. AB - Filamentous fungi undergo complex developmental programs including conidial germination, polarized morphogenesis, and differentiation of sexual and asexual structures. For many fungi, the coordinated completion of development is required for pathogenicity, as specialized morphological structures must be produced by the invading fungus. Ras proteins are highly conserved GTPase signal transducers and function as major regulators of growth and development in eukaryotes. Filamentous fungi typically express two Ras homologues, comprising distinct groups of Ras1-like and Ras2-like proteins based on sequence homology. Recent evidence suggests shared roles for both Ras1 and Ras2 homologues, but also supports the existence of unique functions in the areas of stress response and virulence. This review focuses on the roles played by both Ras protein groups during growth, development, and pathogenicity of a diverse array of filamentous fungi. PMID- 26257822 TI - The efficacy of QingfengGanke granule in treating postinfectious cough in pathogenic wind invading lungs syndrome: a multicenter, randomized, double-blind, placebo-controlled trial. AB - BACKGROUND: Postinfectious cough (PIC) significantly affects cough-related quality of life but still lacks effective treatments. This study aims to investigate the efficacy of QingfengGanke granule (QFGKG) in treating PIC induced by pathogenic wind invading lungs syndrome. METHODS: A multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 180 eligible participants were randomly (1:1:1) assigned to group A (QFGKG 6 g plus QFGKG-matched placebo 6 g), group B (QFGKG 12 g), and group C (QFGKG-matched placebo 12 g). All herbal medications were orally administered twice daily for 10 consecutive days. The primary outcome was time to cough resolution, and secondary outcomes included time to cough alleviation, mean changes in cough symptom score (CSS), visual analogue scale (VAS) score, cough-specific quality of life questionnaire (CQLQ) score, and traditional Chinese medicine (TCM) syndrome score from baseline to Day 10, as well as adverse events. RESULTS: A total of 173 participants were included in the efficacy and safety analyses (group A, n = 57; group B, n = 57; group C, n = 59). The median time to cough resolution in groups A, B, and C was more than 10 days, 8 days, and more than 10 days, respectively (P < 0.0001), and the median time to cough alleviation was 4, 4, and 6 days, respectively (P < 0.0001). Compared with the placebo condition, groups A and B showed significantly greater improvements in CSS (P = 0.0005, P < 0.0001, respectively), VAS (P = 0.0002, P < 0.0001, respectively), CQLQ (P = 0.0258, P = 0.0003, respectively), and TCM syndrome (P = 0.0031, P < 0.0001, respectively). The time to cough resolution was faster in group B compared with group A (P = 0.0091). The adverse event profiles were comparable among the three groups. CONCLUSION: QingfengGanke granule is efficacious in the treatment of PIC induced by pathogenic wind invading lungs syndrome. PMID- 26257823 TI - Ebola in the context of conflict affected states and health systems: case studies of Northern Uganda and Sierra Leone. AB - Ebola seems to be a particular risk in conflict affected contexts. All three of the countries most affected by the 2014-15 outbreak have a complex conflict affected recent history. Other major outbreaks in the recent past, in Northern Uganda and in the Democratic Republic of Congo are similarly afflicted although outbreaks have also occurred in stable settings. Although the 2014-15 outbreak in West Africa has received more attention than almost any other public health issue in recent months, very little of that attention has focused on the complex interaction between conflict and its aftermath and its implications for health systems, the emergence of the disease and the success or failure in controlling it. The health systems of conflict-affected states are characterized by a series of weaknesses, some common to other low and even middle income countries, others specifically conflict-related. Added to this is the burden placed on health systems by the aggravated health problems associated with conflict. Other features of post conflict health systems are a consequence of the global institutional response. Comparing the experience of Northern Uganda and Sierra Leone in the emergence and management of Ebola outbreaks in 2000-1 and in 2014-15 respectively highlights how the various elements of these conflict affected societies came together with international agencies responses to permit the outbreak of the disease and then to successfully contain it (in Northern Uganda) or to fail to do so before a catastrophic cost had been incurred (in Sierra Leone). These case studies have implications for the types of investments in health systems that are needed to enable effective response to Ebola and other zoonotic diseases where they arise in conflict- affected settings. PMID- 26257824 TI - Measuring depression and stigma towards depression and mental health treatment among adolescents in an Arab-American community. AB - There has been limited research that has examined the prevalence of depression and attitudes towards depression and mental health treatment in Arab-American adolescents; we sought to assess these in a predominantly Arab-American community in metro Detroit. A health survey of adolescents aged 12-17 years was conducted (n=98). Participants were recruited from two local community organizations in Dearborn, MI. Depression was assessed by the Patient Health Questionnaire-9 (PHQ 9) Depression Scale, and attitude towards depression and willingness to seek help for mental health conditions were assessed by the Self-Stigma of Depression Scale (SSDS). To assess whether attitudes might be affected by information about mental health treatment, adolescents were randomized to view either an educational video about mental health, or a control video before responding to questions about their willingness to seek help for mental health conditions. Overall, 14% of Arab American adolescents in this study endorsed moderate or moderately severe depression (PHQ-9 >= 11), suggesting a need to increase awareness of and access to mental health services and screening for Arab-American youth. PMID- 26257825 TI - Observations of the genomic landscape beyond 1p19q deletions and EGFR amplification in glioma. AB - BACKGROUND: With recent advancements in molecular techniques, the opportunities to gather whole genome information have increased, even in degraded samples such as FFPE tissues. As a result, a broader view of the genomic landscape of solid tumors may be explored. Whole genome copy number and loss of heterozygosity patterns can advance our understanding of mechanisms and complexity of various tumors. RESULTS: Genome-wide alterations involving copy number changes and loss of heterozygosity were identified in 17 glioma samples with positive FISH results for 1p19q co-deletions (n = 9) or EGFR amplification (n = 8). Gliomas positive for 1p19q co-deletions did not have other frequently recurrent genomic alterations. Additional copy-number alterations were observed in individual cases, and consisted primarily of large-scale changes, including gains or losses of entire chromosomes. The genomic architecture of EGFR amplified gliomas was much more complex, with a high number of gains and losses across the genome. Recurrent alterations in EGFR amplified gliomas were both focal, such as CDKN2A homozygous deletions, and large, such as chromosome 10 loss. CONCLUSIONS: Microarray enabled a broader picture of the genomic alterations occurring in glioma cases. Gliomas with 1p19q co-deletion had a relatively quiet genome, apart from the selected co-deletion. Additional alterations in isolated cases, involved primarily larger aberrations. On the other hand, EGFR amplified cases tended to be more complex and have specific abnormalities associated with the EGFR amplification. Furthermore, 1p19q co-deletions and EGFR amplification associated copy number changes appeared to often be mutually exclusive. PMID- 26257826 TI - Molecular cytogenetic studies characterizing a novel complex karyotype with an uncommon 5q22 deletion in childhood acute myeloid leukemia. AB - Deletions in the long arm of chromosome 5 or loss of the whole chromosome are rare in childhood Acute Myeloid Leukemia (AML) patients. It is also unknown if the wide variety of breakpoints have diverging implications in the patient's outcome. Despite -5/5q- abnormalities have usually been described as a poor prognostic feature, however, the low frequency of -5/5q- in pediatric AML patients limits a full knowledge about this cytogenetic and clinical category, which is an intriguing factor for further research and new findings. Here, we report an AML child showing an uncommon deletion in 5q associated with 2 new abnormalities involving chromosome 2 within a complex karyotype well characterized by several molecular cytogenetic approaches. Our work stimulates upcoming studies with more detailed descriptions about 5q abnormalities to better define its role in the stratification risk of such cytogenetic subgroup in childhood AML. PMID- 26257827 TI - Mutational landscape of mucinous ovarian carcinoma and its neoplastic precursors. AB - BACKGROUND: Mucinous ovarian tumors are an unusual group of rare neoplasms with an apparently clear progression from benign to borderline to carcinoma, yet with a controversial cell of origin in the ovarian surface epithelium. They are thought to be molecularly distinct from other ovarian tumors but there have been no exome-level sequencing studies performed to date. METHODS: To understand the genetic etiology of mucinous ovarian tumors and assess the presence of novel therapeutic targets or pathways, we undertook exome sequencing of 24 tumors encompassing benign (5), borderline (8) and carcinoma (11) histologies and also assessed a validation cohort of 58 tumors for specific gene regions including exons 4-9 of TP53. RESULTS: The predominant mutational signature was of C>T transitions in a NpCpG context, indicative of deamination of methyl-cytosines. As well as mutations in known drivers (KRAS, BRAF and CDKN2A), we identified a high percentage of carcinomas with TP53 mutations (52 %), and recurrent mutations in RNF43, ELF3, GNAS, ERBB3 and KLF5. CONCLUSIONS: The diversity of mutational targets suggests multiple routes to tumorigenesis in this heterogeneous group of tumors that is generally distinct from other ovarian subtypes. PMID- 26257829 TI - Standards-based metadata procedures for retrieving data for display or mining utilizing persistent (data-DOI) identifiers. AB - BACKGROUND: We describe three different procedures based on metadata standards for enabling automated retrieval of scientific data from digital repositories utilising the persistent identifier of the dataset with optional specification of the attributes of the data document such as filename or media type. RESULTS: The procedures are demonstrated using the JSmol molecular visualizer as a component of a web page and Avogadro as a stand-alone modelling program. We compare our methods for automated retrieval of data from a standards-compliant data repository with those currently in operation for a selection of existing molecular databases and repositories. CONCLUSIONS: Our methods illustrate the importance of adopting a standards-based approach of using metadata declarations to increase access to and discoverability of repository-based data. Graphical abstract. PMID- 26257828 TI - Relationship of colorectal cancer awareness and knowledge with colorectal cancer screening. AB - AIM: The aim was to describe the association of awareness and knowledge with participation in colorectal cancer (CRC) screening. MATERIALS & METHODS: Telephone survey research was conducted with South Carolina (USA) residents aged 50-75 years using a 144-item instrument. Data were analyzed with SAS and Stata. Adjusted odds ratios are reported. RESULTS: Respondents (n = 1302) had heard of CRC screening (96%) and exhibited high levels of CRC awareness and knowledge; only 74% had ever been screened. Higher levels of knowledge were associated with a greater likelihood of having ever been screened (odds ratio: 1.05; 95% CI: 1.02 1.41; p < 0.001). CONCLUSION: Results showed high levels of awareness and knowledge, but modest participation in CRC. Transforming awareness and knowledge into CRC screening participation should be a priority. PMID- 26257830 TI - An update on testosterone, HDL and cardiovascular risk in men. AB - Testosterone prescriptions have risen steadily and sharply in the USA despite a lack of clear understanding of the relationship between androgens and cardiovascular disease. In men with increasing age, testosterone levels decline and cardiovascular disease risk goes up. Ties between hypogonadism and cardiovascular disease are suggested by observational data, yet therapy with testosterone replacement has not been shown to mitigate that risk. To the contrary, recent literature has raised concern for increased cardiovascular disease in certain groups of men receiving testosterone therapy. In this article, we review current literature in an attempt to better understand what it suggests is the true relationship between testosterone and cardiovascular disease. We also take a closer look at effects of testosterone on lipids and HDL in particular, to see if this explains the cardiovascular effects seen in clinical studies. PMID- 26257832 TI - AH-7921: the list of new psychoactive opioids is expanded. AB - AH-7921 is a structurally unique synthetic opioid analgesic that has recently entered the drug arena in Europe, the USA, and Japan. Although it was synthesized and patented in the mid-1970s, it was first identified in a seized sample purchased via the Internet in July 2012 and formally brought to the attention of the European Union early warning system in August 2012 by the United Kingdom. Several in vitro experiments and animal model studies established the morphine like analgesic action of AH-7921 as a MU-opioid receptor agonist that has been found to be several times more potent than codeine and at least as potent as morphine. This novel psychoactive substance has already led to eight non-fatal intoxications and 16 deaths in Sweden, the United Kingdom, Norway, and the USA. Thus, AH-7921 is a current public health risk, and better international collaboration, effective legislation and continuous community alertness are needed to tackle this current growing problem. The aim of this review is to summarize the current knowledge about this drug concerning its chemistry, pharmacology, and toxicology, as well as its international legal status. The limited existing analytical methodologies for the determination of AH-7921 in biological samples are also presented. Published or reported AH-7921-related cases, fatalities, or intoxications, and self reports from drug users are reviewed. PMID- 26257831 TI - Comprehensive review of the detection methods for synthetic cannabinoids and cathinones. AB - A number of N-alkyl indole or indazole-3-carbonyl analogs, with modified chemical structures, are distributed throughout the world as synthetic cannabinoids. Like synthetic cannabinoids, cathinone analogs are also abused and cause serious problems worldwide. Acute deaths caused by overdoses of these drugs have been reported. Various analytical methods that can cope with the rapid changes in chemical structures are required for routine analysis and screening of these drugs in seized and biological materials for forensic and clinical purposes. Although many chromatographic methods to analyze each drug have been published, there are only a few articles summarizing these analytical methods. This review presents the various colorimetric detections, immunochemical assays, gas chromatographic-mass spectrometric methods, and liquid chromatographic-mass spectrometric methods proposed for the analysis of synthetic cannabinoids and cathinones. PMID- 26257833 TI - A synthetic cannabinoid FDU-NNEI, two 2H-indazole isomers of synthetic cannabinoids AB-CHMINACA and NNEI indazole analog (MN-18), a phenethylamine derivative N-OH-EDMA, and a cathinone derivative dimethoxy-alpha-PHP, newly identified in illegal products. AB - Six new psychoactive substances were identified together with two other substances (compounds 1-8) in illegal products by our ongoing survey in Japan between January and July 2014. A new synthetic cannabinoid, FDU-NNEI [1-(4 fluorobenzyl)-N-(naphthalen-1-yl)-1H-indole-3-carboxamide, 2], was detected with the newly distributed synthetic cannabinoid FDU-PB-22 (1). Two 2H-indazole isomers of synthetic cannabinoids, AB-CHMINACA 2H-indazole analog (3) and NNEI 2H indazole analog (4), were newly identified with 1H-indazoles [AB-CHMINACA and NNEI indazole analog (MN-18)]. In addition, 2-methylpropyl N-(naphthalen-1-yl) carbamate (5) and isobutyl 1-pentyl-1H-indazole-3-carboxylate (6) were detected in illegal products. Compound 6 is considered to be a by-product of the preparation of NNEI indazole analog from compound 5 and 1-pentyl-1H-indazole. A phenethylamine derivative, N-OH-EDMA [N-hydroxy-3,4-ethylenedioxy-N methylamphetamine, 7], and a cathinone derivative, dimethoxy-alpha-PHP (dimethoxy alpha-pyrrolidinohexanophenone, 8), were newly identified in illegal products. Among them, compounds 1 and 8 have been controlled as designated substances (Shitei-Yakubutsu) under the Pharmaceutical Affairs Law in Japan since August and November 2014, respectively. PMID- 26257834 TI - Postmortem distribution of MAB-CHMINACA in body fluids and solid tissues of a human cadaver. AB - During the latter part of 2014, we experienced an autopsy case in which 5-fluoro ADB, one of the most dangerous synthetic cannabinoids, was identified and quantitated in solid tissues and in three herbal blend products [Forensic Toxicol (2015) 33:112-121]. At that time, although we suspected that there may be some drug(s) other than 5-fluoro-ADB in the herbal products, all trials to find it/them were unsuccessful. Subsequently, we carefully re-examined the presence of other synthetic cannabinoid(s) in the above herbal blend products using accurate mass spectrometry and found two new compounds, 5-fluoro-ADB-PINACA and MAB CHMINACA (Forensic Toxicol. doi: 10.1007/s 11419-015-0264-y). In the present communication, we report the distribution of MAB-CHMINACA in body fluids and solid tissue specimens collected from the same deceased individual (kept frozen at -80 degrees C) as described above for demonstration of 5-fluoro-ADB. Unexpectedly, unchanged MAB-CHMINACA could be identified and quantitated in whole blood and in pericardial fluid specimens, but it was below the detection limit (0.1 ng/ml) in the urine specimen. A higher concentration of MAB-CHMINACA could be found in all of the nine solid tissues; the highest concentration of MAB CHMINACA was found in the liver (156 ng/g), followed by the kidney, pancreas and so on. The compounds were detected in all nine solid tissues; their levels were generally higher than those in the whole blood and pericardial fluid. Contrary to expectations, the concentration of MAB-CHMINACA in the adipose tissue was relatively low. Our results show that the victim smoked one of the three herbal blend products containing both MAB-CHMINACA and 5-fluoro-ADB, resulting in the coexistence of both compounds. It should be concluded that 5-fluoro-ADB and MAB CHMINACA synergically exerted their toxicities, leading to death after a short interval. The differences in the distribution of 5-fluoro-ADB and MAB-CHMINACA among the cadaver specimens were also discussed in view of the structures of both compounds. To our knowledge, this is the first report to demonstrate MAB-CHMINACA in biological/human specimens. PMID- 26257836 TI - Statistical Methods for Generalized Linear Models with Covariates Subject to Detection Limits. AB - Censored observations are a common occurrence in biomedical data sets. Although a large amount of research has been devoted to estimation and inference for data with censored responses, very little research has focused on proper statistical procedures when predictors are censored. In this paper, we consider statistical methods for dealing with multiple predictors subject to detection limits within the context of generalized linear models. We investigate and adapt several conventional methods and develop a new multiple imputation approach for analyzing data sets with predictors censored due to detection limits. We establish the consistency and asymptotic normality of the proposed multiple imputation estimator and suggest a computationally simple and consistent variance estimator. We also demonstrate that the conditional mean imputation method often leads to inconsistent estimates in generalized linear models, while several other methods are either computationally intensive or lead to parameter estimates that are biased or more variable compared to the proposed multiple imputation estimator. In an extensive simulation study, we assess the bias and variability of different approaches within the context of a logistic regression model and compare variance estimation methods for the proposed multiple imputation estimator. Lastly, we apply several methods to analyze the data set from a recently-conducted GenIMS study. PMID- 26257835 TI - CNTN6 copy number variations in 14 patients: a possible candidate gene for neurodevelopmental and neuropsychiatric disorders. AB - BACKGROUND: Neurodevelopmental disorders are impairments of brain function that affect emotion, learning, and memory. Copy number variations of contactin genes (CNTNs), including CNTN3, CNTN4, CNTN5, and CNTN6, have been suggested to be associated with these disorders. However, phenotypes have been reported in only a handful of patients with copy number variations involving CNTNs. METHODS: From January 2009 to January 2013, 3724 patients ascertained through the University of Pittsburgh Medical Center were referred to our laboratory for clinical array comparative genomic hybridization testing. We screened this cohort of patients to identify individuals with the 3p26.3 copy number variations involving the CNTN6 gene, and then retrospectively reviewed the clinical information and family history of these patients to determine the association between the 3p26.3 copy number variations and neurodevelopmental disorders. RESULTS: Fourteen of the 3724 patients had 3p26.3 copy number variations involving the CNTN6 gene. Thirteen of the 14 patients with these CNTN6 copy number variations presented with various neurodevelopmental disorders including developmental delay, autistic spectrum disorders, seizures and attention deficit hyperactivity disorder. Family history was available for 13 of the 14 patients. Twelve of the thirteen families have multiple members with neurodevelopmental and neuropsychiatric disorders including attention deficit hyperactivity disorder, seizures, autism spectrum disorder, intellectual disability, schizophrenia, depression, anxiety, learning disability, and bipolar disorder. CONCLUSIONS: Our findings suggest that deletion or duplication of the CNTN6 gene is associated with a wide spectrum of neurodevelopmental behavioral disorders. PMID- 26257837 TI - Multiple Intravenous Infusions Phase 2a: Ontario Survey. AB - BACKGROUND: Research conducted in earlier phases of this study prospectively identified a number of concerns related to the safe administration of multiple intravenous (IV) infusions in Ontario hospitals. OBJECTIVE: To investigate the potential prevalence of practices or policies that may contribute to the patient safety risks identified in Phase 1b of this study. DATA SOURCES AND REVIEW METHODS: Sixty-four survey responses were analyzed from clinical units where multiple IV infusions may occur (e.g., adult intensive care units). Survey questions were organized according to the topics identified in Phase 1b as potential contributors to patient harm (e.g., labelling practices, patient transfer practices, secondary infusion policies). RESULTS: Survey results indicated suboptimal practices and policies in some clinical units, and variability in a number of infusion practices. Key areas of concern included the following: use of primary IV tubing without back check valves when administering secondary infusions, administration of secondary infusions with/as high-alert continuous IV medications, potential confusion about how IV tubing should be labelled to reflect replacement date and time, interruptions to IV therapy due to IV pump and/or tubing changes when patients are transferred between clinical units, coadministration of continuous or intermittent infusions on central venous pressure monitoring ports, variability in respondents' awareness of the infusion pump's bolus capabilities. LIMITATIONS: Due to the limited sample size, survey responses may not be representative of infusion practices across Ontario. Answers to some questions indicated that the intent of the questions might have been misunderstood. Due to a design error, 1 question about bolus administration methods was not shown to as many respondents as appropriate. CONCLUSIONS: The Ontario survey revealed variability in IV infusion practice across the province and potential opportunities to improve safety. PMID- 26257838 TI - Surface Structure of Bi(111) from Helium Atom Scattering Measurements. Inelastic Close-Coupling Formalism. AB - Elastic and inelastic close-coupling (CC) calculations have been used to extract information about the corrugation amplitude and the surface vibrational atomic displacement by fitting to several experimental diffraction patterns. To model the three-dimensional interaction between the He atom and the Bi(111) surface under investigation, a corrugated Morse potential has been assumed. Two different types of calculations are used to obtain theoretical diffraction intensities at three surface temperatures along the two symmetry directions. Type one consists of solving the elastic CC (eCC) and attenuating the corresponding diffraction intensities by a global Debye-Waller (DW) factor. The second one, within a unitary theory, is derived from merely solving the inelastic CC (iCC) equations, where no DW factor is necessary to include. While both methods arrive at similar predictions for the peak-to-peak corrugation value, the variance of the value obtained by the iCC method is much better. Furthermore, the more extensive calculation is better suited to model the temperature induced signal asymmetries and renders the inclusion for a second Debye temperature for the diffraction peaks futile. PMID- 26257840 TI - Chlorpyrifos Induces the Expression of the Epstein-Barr Virus Lytic Cycle Activator BZLF-1 via Reactive Oxygen Species. AB - Organophosphate pesticides (OPs) are among the most widely used synthetic chemicals for the control of a wide variety of pests, and reactive oxygen species (ROS) caused by OPs may be involved in the toxicity of various pesticides. Previous studies have demonstrated that a reactivation of latent Epstein-Barr virus (EBV) could be induced by oxidative stress. In this study, we investigated whether OPs could reactivate EBV through ROS accumulation. The Raji cells were treated with chlorpyrifos (CPF), one of the most commonly used OPs. Oxidative stress indicators and the expression of the EBV immediate-early gene BZLF-1 were determined after CPF treatment. Our results show that CPF induces oxidative stress as evidenced by decreased malondialdehyde (MDA) level, accompanied by an increase in ROS production, DNA damage, glutathione (GSH) level, and superoxide dismutase (SOD) and catalase (CAT) activity. Moreover, CPF treatment significantly enhances the expression of BZLF-1, and the increased BZLF-1 expression was ameliorated by N-acetylcysteine (NAC) incubation. These results suggest that OPs could contribute to the reactivation of the EBV lytic cycle through ROS induction, a process that may play an important role in the development of EBV-associated diseases. PMID- 26257839 TI - Molecular Events Linking Oxidative Stress and Inflammation to Insulin Resistance and beta-Cell Dysfunction. AB - The prevalence of diabetes mellitus (DM) is increasing worldwide, a consequence of the alarming rise in obesity and metabolic syndrome (MetS). Oxidative stress and inflammation are key physiological and pathological events linking obesity, insulin resistance, and the progression of type 2 DM (T2DM). Unresolved inflammation alongside a "glucolipotoxic" environment of the pancreatic islets, in insulin resistant pathologies, enhances the infiltration of immune cells which through secretory activity cause dysfunction of insulin-secreting beta-cells and ultimately cell death. Recent molecular investigations have revealed that mechanisms responsible for insulin resistance associated with T2DM are detected in conditions such as obesity and MetS, including impaired insulin receptor (IR) signalling in insulin responsive tissues, oxidative stress, and endoplasmic reticulum (ER) stress. The aim of the present review is to describe the evidence linking oxidative stress and inflammation with impairment of insulin secretion and action, which result in the progression of T2DM and other conditions associated with metabolic dysregulation. PMID- 26257842 TI - Limitations of spinal cord stimulation for pain management. PMID- 26257841 TI - Brewers' Rice: A By-Product from Rice Processing Provides Natural Hepatorenal Protection in Azoxymethane-Induced Oxidative Stress in Rats. AB - Brewers' rice, which is known locally as temukut, is a mixture of broken rice, rice bran, and rice germ. Our present study was designed to identify the effect of brewers' rice on the attenuation of liver and kidney damage induced by azoxymethane (AOM). Alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST), creatinine, and urea were evaluated to understand potential hepatoprotective effects and the ability of brewers' rice to attenuate kidney pathology induced by AOM treatment. Liver and kidney tissues were evaluated by hematoxylin and eosin (H&E) staining. Overall analyses revealed that brewers' rice improved the levels of serum markers in a manner associated with better histopathological outcomes, which indicated that brewers' rice could enhance recovery from hepatocyte and kidney damage. Taken together, these results suggest that brewers' rice could be used in future applications to combat liver and kidney disease. PMID- 26257843 TI - Anesthesia and sedation outside of the operating room. AB - Due to rapid evolution and technological advancements, medical personnel now require special training outside of their safe zones. Anesthesiologists face challenges in practicing in locations beyond the operating room. New locations, inadequate monitoring devices, poor assisting staff, unfamiliarity of procedures, insufficient knowledge of basic standards, and lack of experience compromise the quality of patient care. Therefore, anesthesiologists must recognize possible risk factors during anesthesia in nonoperating rooms and familiarize themselves with standards to improve safe practice. This review article emphasizes the need for standardizing hospitals and facilities requiring nonoperating room anesthesia, and encourages anesthesiologists to take the lead in applying these practice guidelines to improve patient outcomes and reduce adverse events. PMID- 26257845 TI - What repeated measures analysis of variances really tells us. AB - This article examined repeated measures analysis of variance (RMANOVA). Within subjects repeated measurements are unavoidable during clinical and experimental investigation, and between- and within-subject variability should be treated separately. Only through proper use and meticulous interpretation can ethical and scientific integrity be guaranteed. The philosophical background of, and knowledge pertaining to, RMANOVA are described in the first half of this text. The sphericity assumption and associated issues are discussed in the latter half. The final section provides a summary measure analysis, which was neglected by P value-dependent interpreters. PMID- 26257844 TI - Practical considerations and nuances in anesthesia for patients undergoing deep brain stimulation implantation surgery. AB - The field of functional neurosurgery has expanded in last decade to include newer indications, new devices, and new methods. This advancement has challenged anesthesia providers to adapt to these new requirements. This review aims to discuss the nuances and practical issues that are faced while administering anesthesia for deep brain stimulation surgery. PMID- 26257846 TI - Use of triazolam and alprazolam as premedication for general anesthesia. AB - BACKGROUND: Triazolam has similar pharmacological properties as other benzodiazepines and is generally used as a sedative to treat insomnia. Alprazolam represents a possible alternative to midazolam for the premedication of surgical patients. The purpose of this study was to evaluate the anxiolytic, sedative, and amnestic properties of triazolam and alprazolam as pre-anesthetic medications. METHODS: Sixty adult patients were randomly allocated to receive oral triazolam 0.25 mg or alprazolam 0.5 mg one hour prior to surgery. A structured assessment interview was performed in the operating room (OR), the recovery room, and the ward. The levels of anxiety and sedation were assessed on a 7-point scale (0 = relaxation to 6 = very severe anxiety) and a 5-point scale (0 = alert to 4 = lack of responsiveness), respectively. The psychomotor performance was estimated using a digit symbol substitution test. As a memory test, we asked the patients the day after the surgery if they remembered being moved from the ward to the OR, and what object we had shown them in the OR. RESULTS: There were no significant differences between the groups with respect to anxiety and sedation. The postoperative interviews showed that 22.2% of the triazolam-treated patients experienced a loss of memory in the OR, against a 0% memory loss in the alprazolam-treated patients. In comparison with alprazolam 0.5 mg, triazolam 0.25 mg produced a higher incidence of amnesia without causing respiratory depression. CONCLUSIONS: Oral triazolam 0.25 mg can be an effective preanesthetic medication for psychomotor performance. PMID- 26257847 TI - The changes of non-invasive hemoglobin and perfusion index of Pulse CO-Oximetry during induction of general anesthesia. AB - BACKGROUND: We hypothesized that induction of general anesthesia using sevoflurane improves the accuracy of non-invasive hemoglobin (SpHb) measurement of Masimo Radical-7(r) Pulse CO-Oximetry by inducing peripheral vasodilation and increasing the perfusion index (PI). The aim of this study is to investigate the change in the SpHb and the PI measured by Rad7 during induction of general anesthesia using sevoflurane. METHODS: The laboratory hemoglobin (Hblab) was measured before surgery by venous blood sampling. The SpHb and the PI was measured twice; before and after the induction of general anesthesia using sevoflurane. The changes of SpHb, Hbbias (Hbbias = SpHb - Hblab), and PI before and after the induction of general anesthesia were analyzed using a paired t test. Also, a Pearson correlation coefficient analysis was used to analyze the correlation between the Hbbias and the PI. RESULTS: The SpHb and the PI were increased after the induction of general anesthesia using sevoflurane. There was a statistically significant change in the Hbbias from -2.8 to -0.7 after the induction of general anesthesia. However, the limit of agreement (2 SD) of the Hbbias did not change after the induction of general anesthesia. The Pearson correlation coefficient between the Hbbias and the PI was not statistically significant. CONCLUSIONS: During induction of general anesthesia using sevoflurane, the accuracy of SpHb measurement was improved and precision was not changed. The correlation between Hbbias and PI was not significant. PMID- 26257848 TI - Position does not affect the optic nerve sheath diameter during laparoscopy. AB - BACKGROUND: Increase in intracranial pressure (ICP) is one of the physiologic changes during laparoscopic surgery, which is known to be associated with positional changes. Changes of ICP can be measured directly by invasive method, but ultrasonographic measurement of optic nerve sheath diameter (ONSD) is known to be a rapidly applicable technique for evaluating ICP. The aim of this study is to investigate the change of ONSD according to the positional change during laparoscopic surgery. METHODS: Female patients scheduled to undergo laparoscopic surgery were enrolled. Fifty-seven patients were assigned according to the position during surgery (Group T: gynecological surgery, Trendelenburg position, n = 27 vs. Group RT: laparoscopic cholecystectomy, Reverse trendelenburg position, n = 30). After induction of anesthesia, ONSD, PaCO2, end-tidal carbon dioxide (ETCO2), and mean arterial pressure (MAP) were measured. Parameters were measured at 6 time points during surgery. RESULTS: There were no significant differences in the demographic data of patients, procedure time, and anesthesia. After pneumoperitoneum and positional change, ONSD, ETCO2, and MAP increased in both groups until 15 min and returned to the baseline. However, no significant differences in changes of ONSD, PaCO2, ETCO2, and MAP were observed between two groups. CONCLUSIONS: ONSD during laparoscopic surgery with pneumoperitoneum increased slightly until 15 minutes, but there were no significant differences according to the position. Increases in ICP during laparoscopic surgery with short period of pneumoperitoneum would be small in disregard of position in patients without intracranial pathology. PMID- 26257849 TI - Changes in blood coagulation after colloid administration in patients undergoing total hip arthroplasty: comparison between pentastarch and tetrastarches, a randomized trial. AB - BACKGROUND: Hydroxyethyl starch (HES) solutions are used as plasma expanders for correcting hypovolemia, but can lead to impaired coagulation. We evaluated the changes in hematological and hemostatic profiles with three types of HES. METHODS: Patients were randomized to receive volume replacement with 10% pentastarch 260/0.45 in 0.9% saline (Group-PEN, n = 25), 6% tetrastarch 130/0.4 in 0.9% saline (Group-TETS, n = 25), or 6% tetrastarch 130/0.4 in a balanced electrolyte solution (Group-TETB, n = 25). Coagulation was assessed using rotational thromboelastometry (ROTEM(r)) and other laboratory tests were performed, including measurements of hematological and hemostatic parameters and electrolytes. RESULTS: Post-operative ROTEM(r) parameters changed toward hypocoagulable states in all groups. The post-operative parameters of EXTEM and FIBTEM were more impaired in Group-PEN than in Group-TETB. The percentage change in INTEM clot formation time (P = 0.004) and alpha-angle (P = 0.003) were smaller in Group-TETS and Group-TETB than in Group-PEN. The percentage change in the FIBTEM maximum clot firmness was greatest in Group-PEN (P = 0.011). The international normalized ratio of prothrombin time (P < 0.001) and the activated partial thromboplastin time (P < 0.001) were significantly prolonged in Group-PEN compared to those of Group-TETB. CONCLUSIONS: The 6% HES 130/0.4 in a balanced electrolyte solution seemed to have less of an impact on blood coagulation than the 10% HES 260/0.45. No differences in hemostatic profile were observed between the balanced electrolyte and saline-based 6% HES 130/0.4. PMID- 26257850 TI - A comparison of postoperative emergence agitation between sevoflurane and thiopental anesthesia induction in pediatric patients. AB - BACKGROUND: This study was performed to compare the incidence of emergence agitation (EA) between inhalation and intravenous anesthesia induction in children after sevoflurane anesthesia. METHODS: In this prospective and double blind study, 100 children aged 3 to 7 years were enrolled. Subjects were randomly assigned to the sevoflurane (Group S) or thiopental (Group T) anesthesia induction groups. Anesthesia was induced using 8% sevoflurane and 4-6 mg/kg thiopental in Groups S and T, respectively. Anesthesia was maintained with nitrous oxide and sevoflurane. The children were evaluated at 5 and 20 min after arrival in the postanesthesia care unit (PACU) with a four-point agitation scale and the Pediatric Anesthesia Emergence Delirium scale. The incidence of EA and administration of the rescue agent were recorded. RESULTS: The incidence of EA was significantly lower in Group T compared to Group S at 5 min after PACU arrival (3/49 patients, 6% vs. 12/47 patients, 26%, P = 0.019). However, there was no difference between the two groups at 20 min after PACU arrival (23/49 vs. 19/47 patients in Group T vs. Group S, P = 0.425). The overall incidence of EA was 60% (28/47 patients) in Group S and 41% (20/49 patients) in Group T (P = 0.102). The number of children who received propofol as a rescue agent was significantly lower in Group T (Group S: 14/47 vs. Group T: 5/49, P = 0.031). CONCLUSIONS: Intravenous anesthesia induction with thiopental reduced the incidence of EA in the early PACU period compared to inhalation induction with sevoflurane in 3- to 7-year-old children undergoing sevoflurane anesthesia. PMID- 26257851 TI - Impact of surgical approach on postoperative delirium in elderly patients undergoing gastrectomy: laparoscopic versus open approaches. AB - BACKGROUND: Postoperative delirium is a frequent complication in elderly patients undergoing major abdominal surgery and is associated with a poor outcome. We compared postoperative delirium in elderly patients following laparoscopic gastrectomy (LG) versus open gastrectomy (OG). METHODS: In total, 130 patients aged >= 65 years with gastric cancer undergoing LG and OG were enrolled prospectively. Postoperative delirium and cognitive status were assessed daily using the Confusion Assessment Method (CAM) and Mini-Mental Status Examination (MMSE), respectively, for 3 days postoperatively. For CAM-positive patients, delirium severity was then assessed using the Delirium Index (DI). RESULTS: In total, 123 subjects (LG, n = 60; OG, n = 63) were included in the analysis. In both groups, the overall incidences of postoperative delirium were similar: 31.6% (19/60) in the LG group and 41.2% (26/63) in the OG group. When considering only those with delirium, the severity, expressed as the highest DI score, was similar between the groups. A decline in cognitive function (reduction in MMSE >= 2 points from baseline) during 3 days postoperatively was observed in 23 patients in the LG group (38.3%) and 27 patients in the OG group (42.9%) (P = 0.744). In both groups, postoperative cognitive decline was significantly associated with postoperative delirium (P < 0.001). CONCLUSIONS: We found that, compared with traditional open gastrectomy, laparoscopic gastrectomy did not reduce either postoperative delirium or cognitive decline in elderly patients with gastric cancer. PMID- 26257852 TI - Comparison of the antiemetic effect of ramosetron with ondansetron in patients undergoing microvascular decompression with retromastoid craniotomy: a preliminary report. AB - BACKGROUND: Microvascular decompression with retromastoid craniotomy carries an especially high risk of postoperative nausea and vomiting. In this study, we compare the antiemetic efficacy of ramosetron and ondansetron in patients undergoing microvascular decompression with retromastoid craniotomy. METHODS: Using balanced anesthesia with sevoflurane and remifentanil infusion, ondansetron 8 mg (group O, n = 31) or ramosetron 0.3 mg (group R, n = 31) was administered at the dural closure. The incidence and severity of postoperative nausea and vomiting, required rescue medications and the incidence of side effects were measured at post-anesthetic care unit, 6, 24 and 48 hours postoperatively. Independent t-tests and the chi-square test or Fisher's exact test were used for statistical analyses. RESULTS: There were no differences in the demographic data between groups, except for a slightly longer anesthetic duration of group R (P = 0.01). The overall postoperative 48 hour incidences of nausea and vomiting were 93.6 and 61.3% (group O), and 87.1 and 51.6% (group R), respectively. Patients in group R showed a less severe degree of nausea (P = 0.02) and a lower incidence of dizziness (P = 0.04) between 6 and 24 hours. CONCLUSIONS: The preventive efficacy of ramosetron when used for postoperative nausea and vomiting was similar to that of ondansetron up to 48 hours after surgery in patients undergoing microvascular decompression with retromastoid craniotomy. A larger randomized controlled trial is needed to confirm our findings. PMID- 26257853 TI - Time course of end-tidal desflurane concentration during delivery and elimination according to the type and location of filters in a semi-closed circuit system. AB - BACKGROUND: The aim of this study was to determine whether the end-tidal concentration of desflurane would be affected by a breathing circuit system filter attached at two different positions in anesthetic breathing circuit systems. METHODS: An artificial lung was ventilated under five different conditions. The first group was without any filter or desflurane (n = 5, sham), the second was with desflurane but without any filter (n = 10, control), the third group had a bacterial filter on the expiratory limb (n = 10), and the fourth and fifth groups had a viral/bacterial filter added on the expiratory limb (n = 10) or at the Y-piece of the breathing circuit (n = 10), respectively. In all groups except the sham, administration of 10% desflurane was performed for 5 minutes and then stopped for 5 minutes. RESULTS: The mean (SD) end-tidal concentration of desflurane for the groups described above peaked at 0 (0), 9.8 (0.1), 9.8 (0.1), 8.5 (0.1), and 6.7% (0.1) (P < 0.001), respectively. There was no difference in the desflurane concentrations and the expired tidal volume over time between the control and bacterial group, but there was a significant difference between the control and the fourth and fifth groups (P < 0.001). CONCLUSIONS: Filters can affect the expiratory desflurane concentration during anesthesia. PMID- 26257854 TI - Therapeutic effects of intravenous administration of bone marrow stromal cells on sevoflurane-induced neuronal apoptosis and neuroinflammation in neonatal rats. AB - BACKGROUND: Sevoflurane exposure during the early postnatal period causes neuroinflammation and neuronal apoptosis in rodents. Bone marrow stromal cells (BMSCs) have been shown to protect and repair the damaged central nervous system, for example in ischemic stroke models. In this study, we investigated whether intravenous administration of BMSCs ameliorated neurodegeneration, induced by sevoflurane exposure, in neonatal rats. METHODS: Sprague-Dawley rat pups (postnatal day 7) were exposed to 2% sevoflurane for 6 h (vehicle group, n = 7). BMSCs were administered 30 min after induction of sevoflurane anesthesia (BMSCs group, n = 7). The pups were exposed to carrier gas only, as a negative control (mock anesthesia group, n = 4). We assessed the therapeutic effects of BMSC treatment by measuring expression of the pro-inflammatory cytokine interleukin-6 (IL-6), and levels of cleaved caspase-3, in brain tissues immediately following sevoflurane anesthesia. RESULTS: Analysis of the cleaved caspase-3 bands revealed that levels of activated caspase-3 were elevated in the vehicle group compared with the mock anesthesia group, indicating that a single exposure to sevoflurane at subclinical concentrations can precipitate neuronal apoptosis. BMSC treatment did not suppress apoptosis induced by sevoflurane exposure (compared with the vehicle group). The vehicle group had higher proinflammatory cytokine IL-6 protein levels compared with the mock anesthesia group, indicating that sevoflurane exposure induces IL-6 expression. BMSC treatment suppressed sevoflurane-induced increases in IL-6 expression, indicating that these cells can inhibit the neuroinflammation induced by sevoflurane exposure (vehicle group vs. BMSC group). CONCLUSIONS: Intravenous administration of BMSCs reduces neuroinflammation, but does not attenuate apoptosis induced by sevoflurane exposure. PMID- 26257855 TI - Correction of malposition of central venous catheter with 9-Fr introducer sheath assisted by mobile type diagnostic X-ray apparatus: a case report. AB - Central venous catheters provide long-term available vascular access. They are useful for central venous pressure monitoring, rapid fluid management, massive transfusion and direct cardiovascular medication, especially in operation. Central venous catheterization is usually performed by the landmark bedside technique without imaging guidance. The complications of central venous catheterization are frequent, which include malposition, pneumothorax, hemothorax, chylothorax, arterial puncture, hematoma, air embolism and infection. Malposition of a central venous catheter is not rare and may cause several complications such as malfunction of the catheter, default measurement of central venous pressure, catheter erosion, thrombophlebitis and cardiac tamponade. In this case, we report a malposition of central venous catheter with 9-Fr introducer sheath which is located in the right subclavian vein via ipsilateral internal jugular vein and the correction of this misplacement assisted by mobile type diagnostic X-ray apparatus (C-arm fluoroscope). PMID- 26257856 TI - Airway management in patient with continuous bleeding lesion of the trachea: a case report. AB - Hemoptysis requires proper treatment to prevent blood aspiration and asphyxiation. If the patient loses consciousness or is anesthetized, the bleeding inside the trachea may continuously flow into the distal part, which may be fatal. Fatal damage resulting from hemoptysis is mainly caused by asphyxiation, and it is important to find the exact location of the bleeding in order to prevent it from spreading to both lungs. However, endotracheal intubation may increase the bleeding by stimulating the bleeding lesion in the respiratory track, and can make airway management more difficult. We report a successful case of airway management using the cuff and Murphy eye of the endotracheal tube in a patient with tracheal bleeding. PMID- 26257857 TI - The use of lung ultrasonography to confirm lung isolation in an infant who underwent emergent video-assisted thoracoscopic surgery: a case report. AB - Video-assisted thoracoscopic surgery for pediatric patients has gained popularity due to better outcomes than open surgery. For this procedure, one-lung ventilation may be necessary to provide an adequate surgical field. Confirming lung isolation is crucial when one-lung ventilation is required. Recently, we experienced a case in which one-lung ventilation was confirmed by ultrasonography using the lung sliding sign and the lung pulse in an infant. Since lung ultrasonography can be performed easily and quickly, it may be a useful method to confirm lung isolation, particularly in emergency surgeries with limited time, devices, and experienced anesthesiologists. PMID- 26257858 TI - Tachycardia-bradycardia syndrome in a patient with atrial fibrillation: a case report. AB - An 83-year-old woman was scheduled for a second transurethral resection of a bladder tumor. The preoperative electrocardiogram evaluation revealed atrial fibrillation with a slow ventricular response (ventricular rate: 59 /min). After intravenous injection of 1% lidocaine 40 mg and propofol 60 mg, the ventricular rate increased to 113 beats/min and then fell rapidly to 27 beats/min. Blood pressure was 70/40 mmHg. Later an atrial fibrillation rhythm, with a ventricular rate of 100-130 beats/min, was observed together with a sinus pause and sinus rhythm with a ventricular rate of 40-50 beats/min. An external pacemaker was applied and set at 60 mA, 40 counts. After the patient regained consciousness, she presented an alert mental state and had no chest symptoms. She was discharged 2 weeks later without complications after insertion of a permanent pacemaker. PMID- 26257859 TI - Is there any quality improvement in the randomized controlled trial abstracts in the Korean Journal of Anesthesiology after the publication of the CONSORT abstract guidelines in 2008? PMID- 26257860 TI - Corrigendum: Occurrence bilateral bronchospasm consequently after unilateral bronchospasm (Korean J Anesthesiol 2013 December 65(6 Suppl): S28-S29). AB - [This corrects the article on p. S28 in vol. 65, PMID: 24478860.]. PMID- 26257861 TI - Synthesis and evaluation of a series of resveratrol analogues as potent anti cancer agents that target tubulin. AB - A series of novel diarylacrylonitrile and trans-stilbene analogues of resveratrol has been synthesized and evaluated for their anticancer activities against a panel of 60 human cancer cell lines. The diarylacrylonitrile analogues 3b and 4a exhibited the most potent anticancer activity of all the analogues synthesized in this study, with GI50 values of < 10 nM against almost all the cell lines in the human cancer cell panel. Compounds 3b and 4a were also screened against the acute myeloid leukemia (AML) cell line, MV4-11, and were found to have potent cytotoxic properties that are likely mediated through inhibition of tubulin polymerization. Results from molecular docking studies indicate a common binding site for 4a and 3b on the 3,3-tubulin heterodimer, with a slightly more favorable binding for 3b compared to 4a; this is consistent with the results from the microtubule assays, which demonstrate that 4a is more potent than 3b in inhibiting tubulin polymerization in MV4-11 cells. Taken together, these data suggest that diarylacrylonitriles 3b and 4a may have potential as antitubulin therapeutics for treatment of both solid and hematological tumors. PMID- 26257862 TI - Involvement of adiponectin in the pathogenesis of dystrophinopathy. AB - BACKGROUND: The hormone adiponectin (ApN) is decreased in the metabolic syndrome, where it plays a key pathogenic role. ApN also exerts some anti-inflammatory effects on skeletal muscles in mice exposed to acute or chronic inflammation. Here, we investigate whether ApN could be sufficiently potent to counteract a severe degenerative muscle disease, with an inflammatory component such as Duchenne muscular dystrophy (DMD). METHODS: Mdx mice (a DMD model caused by dystrophin mutation) were crossed with mice overexpressing ApN in order to generate mdx-ApN mice; only littermates were used. Different markers of inflammation/oxidative stress and components of signaling pathways were studied. Global force was assessed by in vivo functional tests, and muscle injury with Evans Blue Dye (EBD). Eventually, primary cultures of human myotubes were used. RESULTS: Circulating ApN was markedly diminished in mdx mice. Replenishment of ApN strikingly reduced muscle inflammation, oxidative stress, and enhanced the expression of myogenic differentiation markers along with that of utrophin A (a dystrophin analog) in mdx-ApN mice. Accordingly, mdx-ApN mice exhibited higher global force and endurance as well as decreased muscle damage as quantified by curtailed extravasation of EBD in myofibers. These beneficial effects of ApN were recapitulated in human myotubes. ApN mediates its protection via the adiponectin receptor 1 (AdipoR1, the main ApN receptor in muscle) and the AMPK-SIRT1-PGC 1alpha signaling pathway, leading to downregulation of the nuclear factor kappa B (NF-kappaB) and inflammatory genes, together with upregulation of utrophin. CONCLUSIONS: Adiponectin proves to be an extremely powerful hormone capable of protecting the skeletal muscle against inflammation and injury, thereby offering novel therapeutic perspectives for dystrophinopathies. PMID- 26257863 TI - Imaging in neuroendocrine tumors: an update for the clinician. AB - Neuroendocrine tumors are a heterogeneous group of neoplasms that are best worked up and managed using a variety of clinical and imaging studies. They are often diagnosed after they have already metastasized, though this does not necessarily preclude an attempt at curative surgical treatment or surgical debulking. Tumor burden assessment often requires use of multiple imaging modalities including computed tomography, magnetic resonance imaging and ultrasound. Somatostatin receptor-based imaging is also of great utility in looking for primaries and determining the extent of metastatic disease. This paper will review the most common imaging modalities used in the diagnosis and treatment of neuroendocrine tumors. PMID- 26257865 TI - Exploring seascape genetics and kinship in the reef sponge Stylissa carteri in the Red Sea. AB - A main goal of population geneticists is to study patterns of gene flow to gain a better understanding of the population structure in a given organism. To date most efforts have been focused on studying gene flow at either broad scales to identify barriers to gene flow and isolation by distance or at fine spatial scales in order to gain inferences regarding reproduction and local dispersal. Few studies have measured connectivity at multiple spatial scales and have utilized novel tools to test the influence of both environment and geography on shaping gene flow in an organism. Here a seascape genetics approach was used to gain insight regarding geographic and ecological barriers to gene flow of a common reef sponge, Stylissa carteri in the Red Sea. Furthermore, a small-scale (<1 km) analysis was also conducted to infer reproductive potential in this organism. At the broad scale, we found that sponge connectivity is not structured by geography alone, but rather, genetic isolation in the southern Red Sea correlates strongly with environmental heterogeneity. At the scale of a 50-m transect, spatial autocorrelation analyses and estimates of full-siblings revealed that there is no deviation from random mating. However, at slightly larger scales (100-200 m) encompassing multiple transects at a given site, a greater proportion of full-siblings was found within sites versus among sites in a given location suggesting that mating and/or dispersal are constrained to some extent at this spatial scale. This study adds to the growing body of literature suggesting that environmental and ecological variables play a major role in the genetic structure of marine invertebrate populations. PMID- 26257864 TI - Liver cancer oncogenomics: opportunities and dilemmas for clinical applications. AB - Primary liver cancers are among the most rapidly evolving malignant tumors worldwide. An underlying chronic inflammatory liver disease, which precedes liver cancer development for several decades and frequently creates a pro-oncogenic microenvironment, impairs progress in therapeutic approaches. Molecular heterogeneity of liver cancer is potentiated by a crosstalk between epithelial tumor and stromal cells that complicate translational efforts to unravel molecular mechanisms of hepatocarcinogenesis with a drugable intend. Next generation sequencing has greatly advanced our understanding of cancer development. With regards to liver cancer, the unprecedented coverage of next generation sequencing has created a detailed map of genetic alterations and identified key somatic changes such as CTNNB1 and TP53 as well as several previously unrecognized recurrent disease-causing alterations that could contribute to new therapeutic approaches. Importantly, these investigations indicate that a classical oncogene addiction cannot be assumed for primary liver cancer. Therefore, hepatocarcinogenesis can be considered a paradigm suitable for individualized medicine. PMID- 26257866 TI - Evaluation of habitat suitability index models by global sensitivity and uncertainty analyses: a case study for submerged aquatic vegetation. AB - Habitat suitability index (HSI) models are commonly used to predict habitat quality and species distributions and are used to develop biological surveys, assess reserve and management priorities, and anticipate possible change under different management or climate change scenarios. Important management decisions may be based on model results, often without a clear understanding of the level of uncertainty associated with model outputs. We present an integrated methodology to assess the propagation of uncertainty from both inputs and structure of the HSI models on model outputs (uncertainty analysis: UA) and relative importance of uncertain model inputs and their interactions on the model output uncertainty (global sensitivity analysis: GSA). We illustrate the GSA/UA framework using simulated hydrology input data from a hydrodynamic model representing sea level changes and HSI models for two species of submerged aquatic vegetation (SAV) in southwest Everglades National Park: Vallisneria americana (tape grass) and Halodule wrightii (shoal grass). We found considerable spatial variation in uncertainty for both species, but distributions of HSI scores still allowed discrimination of sites with good versus poor conditions. Ranking of input parameter sensitivities also varied spatially for both species, with high habitat quality sites showing higher sensitivity to different parameters than low-quality sites. HSI models may be especially useful when species distribution data are unavailable, providing means of exploiting widely available environmental datasets to model past, current, and future habitat conditions. The GSA/UA approach provides a general method for better understanding HSI model dynamics, the spatial and temporal variation in uncertainties, and the parameters that contribute most to model uncertainty. Including an uncertainty and sensitivity analysis in modeling efforts as part of the decision-making framework will result in better-informed, more robust decisions. PMID- 26257867 TI - Environmental factors prevail over dispersal constraints in determining the distribution and assembly of Trichoptera species in mountain lakes. AB - Aiming to elucidate whether large-scale dispersal factors or environmental species sorting prevail in determining patterns of Trichoptera species composition in mountain lakes, we analyzed the distribution and assembly of the most common Trichoptera (Plectrocnemia laetabilis, Polycentropus flavomaculatus, Drusus rectus, Annitella pyrenaea, and Mystacides azurea) in the mountain lakes of the Pyrenees (Spain, France, Andorra) based on a survey of 82 lakes covering the geographical and environmental extremes of the lake district. Spatial autocorrelation in species composition was determined using Moran's eigenvector maps (MEM). Redundancy analysis (RDA) was applied to explore the influence of MEM variables and in-lake, and catchment environmental variables on Trichoptera assemblages. Variance partitioning analysis (partial RDA) revealed the fraction of species composition variation that could be attributed uniquely to either environmental variability or MEM variables. Finally, the distribution of individual species was analyzed in relation to specific environmental factors using binomial generalized linear models (GLM). Trichoptera assemblages showed spatial structure. However, the most relevant environmental variables in the RDA (i.e., temperature and woody vegetation in-lake catchments) were also related with spatial variables (i.e., altitude and longitude). Partial RDA revealed that the fraction of variation in species composition that was uniquely explained by environmental variability was larger than that uniquely explained by MEM variables. GLM results showed that the distribution of species with longitudinal bias is related to specific environmental factors with geographical trend. The environmental dependence found agrees with the particular traits of each species. We conclude that Trichoptera species distribution and composition in the lakes of the Pyrenees are governed predominantly by local environmental factors, rather than by dispersal constraints. For boreal lakes, with similar environmental conditions, a strong role of dispersal capacity has been suggested. Further investigation should address the role of spatial scaling, namely absolute geographical distances constraining dispersal and steepness of environmental gradients at short distances. PMID- 26257868 TI - Host-associated differentiation in a highly polyphagous, sexually reproducing insect herbivore. AB - Insect herbivores may undergo genetic divergence on their host plants through host-associated differentiation (HAD). Much of what we know about HAD involves insect species with narrow host ranges (i.e., specialists) that spend part or all their life cycle inside their hosts, and/or reproduce asexually (e.g., parthenogenetic insects), all of which are thought to facilitate HAD. However, sexually reproducing polyphagous insects can also exhibit HAD. Few sexually reproducing insects have been tested for HAD, and when they have insects from only a handful of potential host-plant populations have been tested, making it difficult to predict how common HAD is when one considers the entire species' host range. This question is particularly relevant when considering insect pests, as host-associated populations may differ in traits relevant to their control. Here, we tested for HAD in a cotton (Gossypium hirsutum) pest, the cotton fleahopper (CFH) (Pseudatomoscelis seriatus), a sexually reproducing, highly polyphagous hemipteran insect. A previous study detected one incidence of HAD among three of its host plants. We used Amplified fragment length polymorphism (AFLP) markers to assess HAD in CFH collected from an expanded array of 13 host plant species belonging to seven families. Overall, four genetically distinct populations were found. One genetically distinct genotype was exclusively associated with one of the host-plant species while the other three were observed across more than one host-plant species. The relatively low degree of HAD in CFH compared to the pea aphid, another hemipteran insect, stresses the likely importance of sexual recombination as a factor increasing the likelihood of HAD. PMID- 26257869 TI - Integration and scaling of UV-B radiation effects on plants: from DNA to leaf. AB - A process-based model integrating the effects of UV-B radiation through epidermis, cellular DNA, and its consequences to the leaf expansion was developed from key parameters in the published literature. Enhanced UV-B radiation-induced DNA damage significantly delayed cell division, resulting in significant reductions in leaf growth and development. Ambient UV-B radiation-induced DNA damage significantly reduced the leaf growth of species with high relative epidermal absorbance at longer wavelengths and average/low pyrimidine cyclobutane dimers (CPD) photorepair rates. Leaf expansion was highly dependent on the number of CPD present in the DNA, as a result of UV-B radiation dose, quantitative and qualitative absorptive properties of epidermal pigments, and repair mechanisms. Formation of pyrimidine-pyrimidone (6-4) photoproducts (6-4PP) has no effect on the leaf expansion. Repair mechanisms could not solely prevent the UV-B radiation interference with the cell division. Avoidance or effective shielding by increased or modified qualitative epidermal absorptance was required. Sustained increased UV-B radiation levels are more detrimental than short, high doses of UV B radiation. The combination of low temperature and increased UV-B radiation was more significant in the level of UV-B radiation-induced damage than UV-B radiation alone. Slow-growing leaves were more affected by increased UV-B radiation than fast-growing leaves. PMID- 26257870 TI - Effects of grass species and grass growth on atmospheric nitrogen deposition to a bog ecosystem surrounded by intensive agricultural land use. AB - We applied a (15)N dilution technique called "Integrated Total Nitrogen Input" (ITNI) to quantify annual atmospheric N input into a peatland surrounded by intensive agricultural practices over a 2-year period. Grass species and grass growth effects on atmospheric N deposition were investigated using Lolium multiflorum and Eriophorum vaginatum and different levels of added N resulting in increased biomass production. Plant biomass production was positively correlated with atmospheric N uptake (up to 102.7 mg N pot(-1)) when using Lolium multiflorum. In contrast, atmospheric N deposition to Eriophorum vaginatum did not show a clear dependency to produced biomass and ranged from 81.9 to 138.2 mg N pot(-1). Both species revealed a relationship between atmospheric N input and total biomass N contents. Airborne N deposition varied from about 24 to 55 kg N ha(-1) yr(-1). Partitioning of airborne N within the monitor system differed such that most of the deposited N was found in roots of Eriophorum vaginatum while the highest share was allocated in aboveground biomass of Lolium multiflorum. Compared to other approaches determining atmospheric N deposition, ITNI showed highest airborne N input and an up to fivefold exceedance of the ecosystem specific critical load of 5-10 kg N ha(-1) yr(-1). PMID- 26257871 TI - The evolution of obligate sex: the roles of sexual selection and recombination. AB - The evolution of sex is one of the greatest mysteries in evolutionary biology. An even greater mystery is the evolution of obligate sex, particularly when competing with facultative sex and not with complete asexuality. Here, we develop a stochastic simulation of an obligate allele invading a facultative population, where males are subject to sexual selection. We identify a range of parameters where sexual selection can contribute to the evolution of obligate sex: Especially when the cost of sex is low, mutation rate is high, and the facultative individuals do not reproduce sexually very often. The advantage of obligate sex becomes larger in the absence of recombination. Surprisingly, obligate sex can take over even when the population has a lower mean fitness as a result. We show that this is due to the high success of obligate males that can compensate the cost of sex. PMID- 26257872 TI - BEMOVI, software for extracting behavior and morphology from videos, illustrated with analyses of microbes. AB - Microbes are critical components of ecosystems and provide vital services (e.g., photosynthesis, decomposition, nutrient recycling). From the diverse roles microbes play in natural ecosystems, high levels of functional diversity result. Quantifying this diversity is challenging, because it is weakly associated with morphological differentiation. In addition, the small size of microbes hinders morphological and behavioral measurements at the individual level, as well as interactions between individuals. Advances in microbial community genetics and genomics, flow cytometry and digital analysis of still images are promising approaches. They miss out, however, on a very important aspect of populations and communities: the behavior of individuals. Video analysis complements these methods by providing in addition to abundance and trait measurements, detailed behavioral information, capturing dynamic processes such as movement, and hence has the potential to describe the interactions between individuals. We introduce BEMOVI, a package using the R and ImageJ software, to extract abundance, morphology, and movement data for tens to thousands of individuals in a video. Through a set of functions BEMOVI identifies individuals present in a video, reconstructs their movement trajectories through space and time, and merges this information into a single database. BEMOVI is a modular set of functions, which can be customized to allow for peculiarities of the videos to be analyzed, in terms of organisms features (e.g., morphology or movement) and how they can be distinguished from the background. We illustrate the validity and accuracy of the method with an example on experimental multispecies communities of aquatic protists. We show high correspondence between manual and automatic counts and illustrate how simultaneous time series of abundance, morphology, and behavior are obtained from BEMOVI. We further demonstrate how the trait data can be used with machine learning to automatically classify individuals into species and that information on movement behavior improves the predictive ability. PMID- 26257873 TI - Effects of the Epichloe fungal endophyte symbiosis with Schedonorus pratensis on host grass invasiveness. AB - Initial studies of grass-endophyte mutualisms using Schedonorus arundinaceus cultivar Kentucky-31 infected with the vertically transmitted endophyte Epichloe coenophiala found strong, positive endophyte effects on host-grass invasion success. However, more recent work using different cultivars of S. arundinaceus has cast doubt on the ubiquity of this effect, at least as it pertains to S. arundinaceus-E. coenophiala. We investigated the generality of previous work on vertically transmitted Epichloe-associated grass invasiveness by studying a pair of very closely related species: S. pratensis and E. uncinata. Seven cultivars of S. pratensis and two cultivars of S. arundinaceus that were developed with high- or low-endophyte infection rate were broadcast seeded into 2 * 2-m plots in a tilled, old-field grassland community in a completely randomized block design. Schedonorus abundance, endophyte infection rate, and co-occurring vegetation were sampled 3, 4, 5, and 6 years after establishment, and the aboveground invertebrate community was sampled in S. pratensis plots 3 and 4 years after establishment. Endophyte infection did not enable the host grass to achieve high abundance in the plant community. Contrary to expectations, high-endophyte S. pratensis increased plant richness relative to low-endophyte cultivars. However, as expected, high-endophyte S. pratensis marginally decreased invertebrate taxon richness. Endophyte effects on vegetation and invertebrate community composition were inconsistent among cultivars and were weaker than temporal effects. The effect of the grass-Epichloe symbiosis on diversity is not generalizable, but rather specific to species, cultivar, infection, and potentially site. Examining grass-endophyte systems using multiple cultivars and species replicated among sites will be important to determine the range of conditions in which endophyte associations benefit host grass performance and have subsequent effects on co occurring biotic communities. PMID- 26257874 TI - Variation in freshwater fish assemblages along a regional elevation gradient in the northern Andes, Colombia. AB - Studies on elevation diversity gradients have covered a large number of taxa and regions throughout the world; however, studies of freshwater fish are scarce and restricted to examining their changes along a specific gradient. These studies have reported a monotonic decrease in species richness with increasing elevation, but ignore the high taxonomic differentiation of each headwater assemblage that may generate high beta-diversity among them. Here, we analyzed how fish assemblages vary with elevation among regional elevation bands, and how these changes are related to four environmental clines and to changes in the distribution, habitat use, and the morphology of fish species. Using a standardized field sampling technique, we assessed three different diversity and two structural assemblage measures across six regional elevation bands located in the northern Andes (Colombia). Each species was assigned to a functional group based on its body shape, habitat use, morphological, and/or behavioral adaptations. Additionally, at each sampling site, we measured four environmental variables. Our analyses showed: (1) After a monotonic decrease in species richness, we detected an increase in richness in the upper part of the gradient; (2) diversity patterns vary depending on the diversity measure used; (3) diversity patterns can be attributed to changes in species distribution and in the richness and proportions of functional groups along the regional elevation gradient; and (4) diversity patterns and changes in functional groups are highly correlated with variations in environmental variables, which also vary with elevation. These results suggest a novel pattern of variation in species richness with elevation: Species richness increases at the headwaters of the northern Andes owing to the cumulative number of endemic species there. This highlights the need for large-scale studies and has important implications for the aquatic conservation of the region. PMID- 26257875 TI - Temporal dynamics of seed excretion by wild ungulates: implications for plant dispersal. AB - Dispersal is a key process in metapopulation dynamics as it conditions species' spatial responses to gradients of abiotic and biotic conditions and triggers individual and gene flows. In the numerous plants that are dispersed through seed consumption by herbivores (endozoochory), the distance and effectiveness of dispersal is determined by the combined effects of seed retention time in the vector's digestive system, the spatial extent of its movements, and the ability of the seeds to germinate once released. Estimating these three parameters from experimental data is therefore crucial to calibrate mechanistic metacommunity models of plant-herbivore interactions. In this study, we jointly estimated the retention time and germination probability of six herbaceous plants transported by roe deer (Capreolus capreolus), red deer (Cervus elaphus), and wild boar (Sus scrofa) through feeding experiments and a Bayesian dynamic model. Retention time was longer in the nonruminant wild boar (>36 h) than in the two ruminant species (roe deer: 18-36 h, red deer: 3-36 h). In the two ruminants, but not in wild boar, small and round seeds were excreted faster than large ones. Low germination probabilities of the excreted seeds reflected the high cost imposed by endozoochory on plant survival. Trait-mediated variations in retention time and germination probability among animal and plant species may impact plant dispersal distances and interact with biotic and abiotic conditions at the release site to shape the spatial patterns of dispersed plant species. PMID- 26257876 TI - Application of a Bayesian nonparametric model to derive toxicity estimates based on the response of Antarctic microbial communities to fuel-contaminated soil. AB - Ecotoxicology is primarily concerned with predicting the effects of toxic substances on the biological components of the ecosystem. In remote, high latitude environments such as Antarctica, where field work is logistically difficult and expensive, and where access to adequate numbers of soil invertebrates is limited and response times of biota are slow, appropriate modeling tools using microbial community responses can be valuable as an alternative to traditional single-species toxicity tests. In this study, we apply a Bayesian nonparametric model to a soil microbial data set acquired across a hydrocarbon contamination gradient at the site of a fuel spill in Antarctica. We model community change in terms of OTUs (operational taxonomic units) in response to a range of total petroleum hydrocarbon (TPH) concentrations. The Shannon diversity of the microbial community, clustering of OTUs into groups with similar behavior with respect to TPH, and effective concentration values at level x, which represent the TPH concentration that causes x% change in the community, are presented. This model is broadly applicable to other complex data sets with similar data structure and inferential requirements on the response of communities to environmental parameters and stressors. PMID- 26257877 TI - Wind-mediated horseweed (Conyza canadensis) gene flow: pollen emission, dispersion, and deposition. AB - Horseweed (Conyza canadensis) is a problem weed in crop production because of its evolved resistance to glyphosate and other herbicides. Although horseweed is mainly self-pollinating, glyphosate-resistant (GR) horseweed can pollinate glyphosate-susceptible (GS) horseweed. To the best of our knowledge, however, there are no available data on horseweed pollen production, dispersion, and deposition relative to gene flow and the evolution of resistance. To help fill this knowledge gap, a 43-day field study was performed in Champaign, Illinois, USA in 2013 to characterize horseweed atmospheric pollen emission, dispersion, and deposition. Pollen concentration and deposition, coupled with atmospheric data, were measured in a source field (180 m by 46 m) and its surrounding areas up to 1 km downwind horizontally and up to 100 m vertically. The source strength (emission rate) ranged from 0 to 140 pollen grains per plant per second (1170 to 2.1*10(6) per plant per day). For the life of the study, the estimated number of pollen grains generated from this source field was 10.5*10(10) (2.3*10(6) per plant). The release of horseweed pollen was not strongly correlated to meteorological data and may be mainly determined by horseweed physiology. Horseweed pollen reached heights of 80 to100 m, making long-distance transport possible. Normalized (by source data) pollen deposition with distance followed a negative-power exponential curve. Normalized pollen deposition was 2.5% even at 480 m downwind from the source edge. Correlation analysis showed that close to or inside the source field at lower heights (<=3 m) vertical transport was related to vertical wind speed, while horizontal pollen transport was related to horizontal wind speed. High relative humidity prevented pollen transport at greater heights (3-100 m) and longer distances (0-1000 m) from the source. This study can contribute to the understanding of how herbicide-resistance weeds or invasive plants affect ecology through wind-mediated pollination and invasion. PMID- 26257878 TI - Consumer trait variation influences tritrophic interactions in salt marsh communities. AB - The importance of intraspecific variation has emerged as a key question in community ecology, helping to bridge the gap between ecology and evolution. Although much of this work has focused on plant species, recent syntheses have highlighted the prevalence and potential importance of morphological, behavioral, and life history variation within animals for ecological and evolutionary processes. Many small-bodied consumers live on the plant that they consume, often resulting in host plant-associated trait variation within and across consumer species. Given the central position of consumer species within tritrophic food webs, such consumer trait variation may play a particularly important role in mediating trophic dynamics, including trophic cascades. In this study, we used a series of field surveys and laboratory experiments to document intraspecific trait variation in a key consumer species, the marsh periwinkle Littoraria irrorata, based on its host plant species (Spartina alterniflora or Juncus roemerianus) in a mixed species assemblage. We then conducted a 12-week mesocosm experiment to examine the effects of Littoraria trait variation on plant community structure and dynamics in a tritrophic salt marsh food web. Littoraria from different host plant species varied across a suite of morphological and behavioral traits. These consumer trait differences interacted with plant community composition and predator presence to affect overall plant stem height, as well as differentially alter the density and biomass of the two key plant species in this system. Whether due to genetic differences or phenotypic plasticity, trait differences between consumer types had significant ecological consequences for the tritrophic marsh food web over seasonal time scales. By altering the cascading effects of the top predator on plant community structure and dynamics, consumer differences may generate a feedback over longer time scales, which in turn influences the degree of trait divergence in subsequent consumer populations. PMID- 26257879 TI - Discovery-dominance trade-off among widespread invasive ant species. AB - Ants are among the most problematic invasive species. They displace numerous native species, alter ecosystem processes, and can have negative impacts on agriculture and human health. In part, their success might stem from a departure from the discovery-dominance trade-off that can promote co-existence in native ant communities, that is, invasive ants are thought to be at the same time behaviorally dominant and faster discoverers of resources, compared to native species. However, it has not yet been tested whether similar asymmetries in behavioral dominance, exploration, and recruitment abilities also exist among invasive species. Here, we establish a dominance hierarchy among four of the most problematic invasive ants (Linepithema humile, Lasius neglectus, Wasmannia auropunctata, Pheidole megacephala) that may be able to arrive and establish in the same areas in the future. To assess behavioral dominance, we used confrontation experiments, testing the aggressiveness in individual and group interactions between all species pairs. In addition, to compare discovery efficiency, we tested the species' capacity to locate a food resource in a maze, and the capacity to recruit nestmates to exploit a food resource. The four species differed greatly in their capacity to discover resources and to recruit nestmates and to dominate the other species. Our results are consistent with a discovery-dominance trade-off. The species that showed the highest level of interspecific aggressiveness and dominance during dyadic interactions. PMID- 26257880 TI - Temporal autocorrelation in host density increases establishment success of parasitoids in an experimental system. AB - Environmental variation is classically expected to affect negatively population growth and to increase extinction risk, and it has been identified as a major determinant of establishment failures in the field. Yet, recent theoretical investigations have shown that the structure of environmental variation and more precisely the presence of positive temporal autocorrelation might alter this prediction. This is particularly likely to affect the establishment dynamics of biological control agents in the field, as host-parasitoid interactions are expected to induce temporal autocorrelation in host abundance. In the case where parasitoid populations display overcompensatory dynamics, the presence of such positive temporal autocorrelation should increase their establishment success in a variable environment. We tested this prediction in laboratory microcosms by introducing parasitoids to hosts whose abundances were manipulated to simulate uncorrelated or positively autocorrelated variations in carrying capacity. We found that environmental variability decreased population size and increased parasitoid population variance, which is classically expected to extinction risk. However, although exposed to significant environmental variation, we found that parasitoid populations experiencing positive temporal autocorrelation in host abundance were more likely to persist than populations exposed to uncorrelated variation. These results confirm that environmental variation is a key determinant of extinction dynamics that can have counterintuitive effects depending on its autocorrelation structure. PMID- 26257881 TI - Detectability of landscape effects on recolonization increases with regional population density. AB - Variation in population size over time can influence our ability to identify landscape-moderated differences in community assembly. To date, however, most studies at the landscape scale only cover snapshots in time, thereby overlooking the temporal dynamics of populations and communities. In this paper, we present data that illustrate how temporal variation in population density at a regional scale can influence landscape-moderated variation in recolonization and population buildup in disturbed habitat patches. Four common insect species, two omnivores and two herbivores, were monitored over 8 years in 10 willow short rotation coppice bio-energy stands with a four-year disturbance regime (coppice cycle). The population densities in these regularly disturbed stands were compared to densities in 17 undisturbed natural Salix cinerea (grey willow) stands in the same region. A time series approach was used, utilizing the natural variation between years to statistically model recolonization as a function of landscape composition under two different levels of regional density. Landscape composition, i.e. relative amount of forest vs. open agricultural habitats, largely determined the density of re-colonizing populations following willow coppicing in three of the four species. However, the impact of landscape composition was not detectable in years with low regional density. Our results illustrate that landscape-moderated recolonization can change over time and that considering the temporal dynamics of populations may be crucial when designing and evaluating studies at landscape level. PMID- 26257882 TI - Differences in style length confer prezygotic isolation between two dioecious species of Silene in sympatry. AB - One fundamental signature of reinforcement is elevated prezygotic reproductive isolation between related species in sympatry relative to allopatry. However, this alone is inadequate evidence for reinforcement, as traits conferring reproductive isolation can occur as a by-product of other forces. We conducted crosses between Silene latifolia and S. diclinis, two closely related dioecious flowering plant species. Crosses with S. latifolia mothers from sympatry exhibited lower seed set than mothers from five allopatric populations when S. diclinis was the father. However, two other allopatric populations also exhibited low seed set. A significant interaction between style length and sire species revealed that seed set declined as style length increased when interspecific, but not intraspecific, fathers where used. Moreover, by varying the distance pollen tubes had to traverse, we found interspecific pollen placement close to the ovary resulted in seed set in both long- and short-styled S. latifolia mothers. Our results reveal that the long styles of S. latifolia in sympatry with S. diclinis contribute to the prevention of hybrid formation. We argue that forces other than reinforcing selection are likely to be responsible for the differences in style length seen in sympatry. PMID- 26257883 TI - Inbreeding and adaptive plasticity: an experimental analysis on predator-induced responses in the water flea Daphnia. AB - Several studies have emphasized that inbreeding depression (ID) is enhanced under stressful conditions. Additionally, one might imagine a loss of adaptively plastic responses which may further contribute to a reduction in fitness under environmental stress. Here, we quantified ID in inbred families of the cyclical parthenogen Daphnia magna in the absence and presence of fish predation risk. We test whether predator stress affects the degree of ID and if inbred families have a reduced capacity to respond to predator stress by adaptive phenotypic plasticity. We obtained two inbred families through clonal selfing within clones isolated from a fish pond. After mild purging under standardized conditions, we compared life history traits and adaptive plasticity between inbred and outbred lineages (directly hatched from the natural dormant egg bank of the same pond). Initial purging of lineages under standardized conditions differed among inbred families and exceeded that in outbreds. The least purged inbred family exhibited strong ID for most life history traits. Predator-induced stress hardly affected the severity of ID, but the degree to which the capacity for adaptive phenotypic plasticity was retained varied strongly among the inbred families. The least purged family overall lacked the capacity for adaptive phenotypic plasticity, whereas the family that suffered only mild purging exhibited a potential for adaptive plasticity that was comparable to the outbred population. We thus found that inbred offspring may retain the capacity to respond to the presence of fish by adaptive phenotypic plasticity, but this strongly depends on the parental clone engaging in selfing. PMID- 26257884 TI - Identifying signatures of sexual selection using genomewide selection components analysis. AB - Sexual selection must affect the genome for it to have an evolutionary impact, yet signatures of selection remain elusive. Here we use an individual-based model to investigate the utility of genome-wide selection components analysis, which compares allele frequencies of individuals at different life history stages within a single population to detect selection without requiring a priori knowledge of traits under selection. We modeled a diploid, sexually reproducing population and introduced strong mate choice on a quantitative trait to simulate sexual selection. Genome-wide allele frequencies in adults and offspring were compared using weighted F ST values. The average number of outlier peaks (i.e., those with significantly large F ST values) with a quantitative trait locus in close proximity ("real" peaks) represented correct diagnoses of loci under selection, whereas peaks above the F ST significance threshold without a quantitative trait locus reflected spurious peaks. We found that, even with moderate sample sizes, signatures of strong sexual selection were detectable, but larger sample sizes improved detection rates. The model was better able to detect selection with more neutral markers, and when quantitative trait loci and neutral markers were distributed across multiple chromosomes. Although environmental variation decreased detection rates, the identification of real peaks nevertheless remained feasible. We also found that detection rates can be improved by sampling multiple populations experiencing similar selection regimes. In short, genome-wide selection components analysis is a challenging but feasible approach for the identification of regions of the genome under selection. PMID- 26236464 TI - Anterior and posterior subareas of the dorsolateral frontal cortex in socially relevant decisions based on masked affect expressions. AB - Socially-relevant decisions are based on clearly recognizable but also not consciously accessible affective stimuli. We studied the role of the dorsolateral frontal cortex (DLFC) in decision-making on masked affect expressions using functional magnetic resonance imaging. Our paradigm permitted us to capture brain activity during a pre-decision phase when the subjects viewed emotional expressions below the threshold of subjective awareness, and during the decision phase, which was based on verbal descriptions as the choice criterion. Using meta analytic connectivity modeling, we found that the preparatory phase of the decision was associated with activity in a right-posterior portion of the DLFC featuring co-activations in the left-inferior frontal cortex. During the subsequent decision a right-anterior and more dorsal portion of the DLFC became activated, exhibiting a different co-activation pattern. These results provide evidence for partially independent sub-regions within the DLFC, supporting the notion of dual associative processes in intuitive judgments. PMID- 26257889 TI - Chemical Synthesis of the Tumor-Associated Globo H Antigen. AB - A derivative of the tumor-associated globo H antigen, a complex hexasaccharide, was synthesized by a convergent and efficient [3+2+1] strategy using various glycosylation methods. All glycosylation reactions afforded good to excellent yields and outstanding stereoselectivity, including the installation of cis alpha linked D-galactose and L-fucose. The longest linear sequence for this synthesis was 11 steps from a galactose derivative 11 to give an overall yield of 2.6%. The synthetic target had a free and reactive amino group at the glycan reducing end, facilitating its conjugation with other molecules for various applications. PMID- 26257888 TI - Characterization of the Binding of the Finland Trityl Radical with Bovine Serum Albumin. AB - Understanding the interactions of trityl radicals with proteins is required to expand their biomedical applications. In this work, we demonstrate that the Finland trityl radical CT-03 binds to bovine serum albumin (BSA) in aqueous solution. Upon binding with BSA, CT-03 exhibits a much broader electron paramagnetic resonance (EPR) signal and this line broadening can be reversed by proteolysis of the BSA. The binding induces a red-shift of the maximal UV-Vis absorbance wavelength of CT-03 around 470 nm, likely due to localization of CT-03 in the relatively hydrophobic region of the protein. The interaction between CT 03 and BSA is driven by a hydrophobic interaction with an estimated binding constant of 2.18 *105 M-1 at 298 K. Furthermore, only one CT-03 is bound to each molecule of BSA and the binding site is determined to be the sub-domain IIA (Sudlow's site I). This protein binding of the trityl probe to albumin can be used to study the structure and function of albumin and also must be considered for its use as an in vivo imaging agent or spin label. PMID- 26257890 TI - Purification and Structural Characterization of "Simple Catechol", the NGAL Siderocalin Siderophore in Human Urine. AB - The identification of ligands that bind the protein Neutrophil Gelatinase Associated Lipocalin (NGAL, Siderocalin, Lipocalin-2) have helped to elucidate its function. NGAL-Siderocalin binds and sequesters the iron loaded bacterial siderophore enterochelin (Ent), defining the protein as an innate immune effector. Simple metabolic catechols can also form tight complexes with NGAL Siderocalin and ferric iron, suggesting that the protein may act as an iron scavenger even in the absence of Ent. While different catechols have been detected in human urine, they have not been directly purified from a biofluid and demonstrated to ligate iron with NGAL-Siderocalin. This paper describes a "natural products" approach to identify small molecules that mediate iron binding to NGAL-Siderocalin. A 10K filtrate of human urine was subjected to multiple steps of column chromatography and reverse-phase HPLC, guided by NGAL-Siderocalin iron binding assays and LC-MS detection. The co-factor forming a ternary structure with iron and NGAL-Siderocalin was identified as authentic simple catechol (dihydroxybenze) by ESI-HR-Mass, UV, and NMR spectrometric analysis. Comparison of the binding strengths of different catechols demonstrated that the vicinal-dihydroxyl groups were the key functional groups and that steric compatibilities of the catechol ring have the strongest effect on binding. Although catechol was a known NGAL-Siderocalin co-factor, our purification directly confirmed its presence in urine as well as its capacity to serve as an iron trap with NGAL-Siderocalin. PMID- 26236464 TI - Anterior and posterior subareas of the dorsolateral frontal cortex in socially relevant decisions based on masked affect expressions. AB - Socially-relevant decisions are based on clearly recognizable but also not consciously accessible affective stimuli. We studied the role of the dorsolateral frontal cortex (DLFC) in decision-making on masked affect expressions using functional magnetic resonance imaging. Our paradigm permitted us to capture brain activity during a pre-decision phase when the subjects viewed emotional expressions below the threshold of subjective awareness, and during the decision phase, which was based on verbal descriptions as the choice criterion. Using meta analytic connectivity modeling, we found that the preparatory phase of the decision was associated with activity in a right-posterior portion of the DLFC featuring co-activations in the left-inferior frontal cortex. During the subsequent decision a right-anterior and more dorsal portion of the DLFC became activated, exhibiting a different co-activation pattern. These results provide evidence for partially independent sub-regions within the DLFC, supporting the notion of dual associative processes in intuitive judgments. PMID- 26257891 TI - Tip-Based Nanofabrication of Arbitrary Shapes of Graphene Nanoribbons for Device Applications. AB - Graphene nanoribbons (GNRs) have promising applications in future nanoelectronics, chemical sensing and electrical interconnects. Although there are quite a few GNR nanofabrication methods reported, a rapid and low-cost fabrication method that is capable of fabricating arbitrary shapes of GNRs with good-quality is still in demand for using GNRs for device applications. In this paper, we present a tip-based nanofabrication method capable of fabricating arbitrary shapes of GNRs. A heated atomic force microscope (AFM) tip deposits polymer nanowires atop a CVD-grown graphene surface. The polymer nanowires serve as an etch mask to define GNRs through one step of oxygen plasma etching similar to a photoresist in conventional photolithography. Various shapes of GNRs with either linear or curvilinear features are demonstrated. The width of the GNR is around 270 nm and is determined by the width of the depositing polymer nanowire, which we estimate can be scaled down 15 nms. We characterize our TBN-fabricated GNRs using Raman spectroscopy and I-V measurements. The measured sheet resistances of our GNRs fall within the range of 1.65 kOmega/?-1 - 2.64 kOmega/? 1, in agreement with previously reported values. Furthermore, we determined the high-field breakdown current density of GNRs to be approximately 2.94*108 A/cm2. This TBN process is seamlessly compatible with existing nanofabrication processes, and is particularly suitable for fabricating GNR based electronic devices including next generation DNA sequencing technologies and beyond silicon field effect transistors. PMID- 26257892 TI - Synthesis of surface nano-molecularly imprinted polymers for sensitive baicalin detection from biological samples. AB - Surface molecularly imprinted polymers (MIP@SBA-15) imprinted on the surface of hybrid nanostructured organic/inorganic materials (SBA-15) were prepared for the selective extraction and detection of baicalin (BA) from biological samples. The surface morphologies and characteristics of the imprinted and non-imprinted polymers were characterized by Fourier transform infrared (FT-IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermo gravimetric analysis (TGA) and nitrogen adsorption-desorption isotherms. The results indicated that the polymers were successfully grafted on the surface of SBA-15 and possessed a highly ordered mesoporous structure. In binding tests, MIP@SBA-15 reached saturated adsorption within 80 min and exhibited significant specific recognition toward BA with large adsorption capacity. Meanwhile, the prepared MIP@SBA-15 was used as a selective sorbent for solid-phase extraction of BA from biological samples. Recoveries of BA from the liver and spleen ranged from 90.6% to 90.9% with RSD < 3.7%. All these results reveal that this method is simple, rapid and sensitive for effectively extracting and detecting trace BA in biological samples. PMID- 26257893 TI - Biological relevance of oxidative debris present in as-prepared graphene oxide. AB - The influence of oxidative debris (OD) present in as-prepared graphene oxide (GO) suspensions on proteins and its toxicity to human embryonic kidney cells (HEK 293T) are reported here. The OD was removed by repeated washing with aqueous ammonia to produce the corresponding base-washed GO (bwGO). The loading (w/w) of bovine serum albumin (BSA) was increased by 85% after base washing, whereas the loading of hemoglobin (Hb) and lysozyme (Lyz), respectively, was decreased by 160% and 100%. The secondary structures of 13 different proteins bound to bwGO were compared with the corresponding proteins bound to GO using the UV circular dichroism spectroscopy. There was a consistent loss of protein secondary structure with bwGO when compared with proteins bound to GO, but no correlation between either the isoelectric point or hydrophobicity of the protein and the extent of structure loss was observed. All enzymes bound to bwGO and GO indicated significant activities, and a strong correlation between the enzymatic activity and the extent of structure retention was noted, regardless of the presence or absence of OD. At low loadings (<100 MUg/mL) both GO and bwGO showed excellent cell viability but substantial cytotoxicity (~40% cell death) was observed at high loadings (>100 MUg/mL). In control studies, OD by itself did not alter the growth rate even after a 48-h incubation. Thus, the presence of OD in GO played a very important role in controlling the chemical and biological nature of the protein-GO interface and the presence of OD in GO improved its biological compatibility when compared to bwGO. PMID- 26257894 TI - Small lipopeptides possess anti-biofilm capability comparable to daptomycin and vancomycin. AB - Antibiotic resistance, to a large extent, is related to the formation of bacterial biofilms. Thus, compounds with anti-biofilm capability are of practical importance. Inspired by the recent discovery of two amino acid lipopeptides from marine bacteria, we constructed a family of small lipopeptides with 2-3 amino acids. While no antimicrobial activity was found for anionic lipopeptides, cationic candidates are potent against Staphylococcus strains, such as methicillin-resistant Staphylococcus aureus (MRSA) USA200, USA300, USA400, UAMS 1, Newman, and Mu50. In the simplest design, two lysines (C14-KK) or three arginines (C14-RRR) attached to an acyl chain of 14 carbons were sufficient to make the compounds antimicrobial. These simple lipopeptides are inherently stable towards S. aureus V8 proteinase and fungal proteinase K, more soluble in water, and more selective than other lipopeptides containing a mixture of hydrophobic and cationic amino acids. Furthermore, the activity of C14-RRR was not compromised by salts, serum, or a change in pH. Live cell experiments revealed that these lipopeptides, with a detergent-like structure, killed bacteria rapidly by targeting cell membranes. Importantly, these compounds were also able to inhibit biofilm formation and could even disrupt preformed biofilms of clinically relevant MRSA strains with an in vitro efficacy comparable to daptomycin and vancomycin. These results indicate that small lipopeptides are potentially useful candidates for preventing or eliminating bacterial biofilms alone or in combination with daptomycin or vancomycin. PMID- 26257896 TI - Annals of Medicine and Surgery - Educating and Developing Leading Physicians and Surgeons. PMID- 26257895 TI - Update on deep brain stimulation in Parkinson's disease. AB - Deep brain stimulation (DBS) is considered a safe and well tolerated surgical procedure to alleviate Parkinson's disease (PD) and other movement disorders symptoms along with some psychiatric conditions. Over the last few decades DBS has been shown to provide remarkable therapeutic effect on carefully selected patients. Although its precise mechanism of action is still unknown, DBS improves motor functions and therefore quality of life. To date, two main targets have emerged in PD patients: the globus pallidus pars interna and the subthalamic nucleus. Two other targets, the ventralis intermedius and zona incerta have also been selectively used, especially in tremor-dominant PD patients. The main indications for PD DBS have traditionally been motor fluctuations, debilitating medication induced dyskinesias, unpredictable "off time" state, and medication refractory tremor. Medication refractory tremor and intolerable dyskinesia are potential palliative indications. Besides aforementioned targets, the brainstem pedunculopontine nucleus (PPN) is under investigation for the treatment of ON state freezing of gait and postural instability. In this article, we will review the most recent literature on DBS therapy for PD, including cutting-edge advances and data supporting the role of DBS in advanced neural-network modulation. PMID- 26257897 TI - Annals of Medicine and Surgery - A modern Journal for Modern Trainees. AB - At its core, the purpose of healthcare is simple: to maximise quality and quantity of life. To achieve this vision, doctors have assumed an array of roles across a number of domains beyond the one-to-one patient-doctor interaction. Such domains include; teaching, research, leadership, management and clinical governance to name but a few. These roles and the healthcare systems in which they operate, have evolved over time to meet demand from patients, the profession, government and regulators. Further evolution is needed as we move into the 21st century to deal with the "perfect storm" of expensive technological advances, economic challenges and epidemiological changes.(1) It is the trainees and students of today who will drive this progress in the future. Journals are a gateway to scientific progress and we believe there is a need for a journal to educate and develop the knowledge, skills and attitudes of trainees and students. Furthermore, over the past few years, the very nature of scientific journal publication has come under scrutiny.(2) Hence we seek to establish a modern journal that deals with the challenges and opportunities of the 21st century. PMID- 26257898 TI - Should Doctors Be More Careful with Social Media? PMID- 26257899 TI - Neurosurgery in the Past and Future. An Appraisal. PMID- 26257900 TI - The Roles of the Learned Societies in Improving Quality of Life in the context of Globalisation. AB - This manuscript is an adapted text of an address to the Thai Royal Institution during the 'International Conference for the Celebrations on the Auspicious Occasion of His Majesty the King's 7th Cycle Birthday Anniversary'. There are many problems facing the world in the context of increasing globalization. "Thou shalt love thy neighbour as thyself." The Old Testament (Leviticus 19:18), reminds us all that whatever race, religion, or culture we come from, the simple command to love ones neighbour as ourselves, is the bedrock of civilization. In response to this command, we have to ask ourselves two simple questions; how do we best express our love, and who do we consider to be our neighbour? If one loves oneself, then what is the single most important gift one would grant him/herself? Most would say the gift of good health. Therefore, if one loves others, then the gift one wants for them is also good health. These others, who one should love in an unconditional way, are one's parents, spouses, children, and grandchildren. But to whom does this duty or commandment to love extend? How wide is this circle of love? Is it the immediate family, the extended family, our village, our tribe, or our nation state? PMID- 26257901 TI - Has the Human Genome Project Delivered for Healthcare? PMID- 26257902 TI - Commentary on: "Physical activity education in the undergraduate curricula of all UK medical schools. Are tomorrow's doctors equipped to follow clinical guidelines?". PMID- 26257903 TI - Commentary On: "Surgical Smoke - A Health Hazard in the Operating Theatre: A Study to Quantify Exposure and a Survey of the Use of Smoke Extractor Systems in UK Plastic Surgery Units". PMID- 26257904 TI - Handover in Trauma and Orthopaedic Surgery - A Human Factors Assessment. AB - Handovers permeate healthcare delivery systems. They are critical for patient safety and continuity of care, but also for logistics and clinical efficiency. Poor handovers can cause reduced efficiency, delayed discharge or time to operation, and contributes to patient harm. The Objective was to conduct a human factors assessment (HFA) using a systems approach to study the handover process at an Orthopaedic unit, determine barriers to information transfer, and suggest improvements. A direct observation model was used to help provide insights on the evening handover process. A Systems Engineering Initiative for Patient Safety (SEIPS) model was used to provide a framework. A total of ten handover sessions were observed and the junior doctors were interviewed using a semi-structured approach. Participants had two chief centres of complaint: workspace and environmental issues (such as a small, hot, uncomfortable room), and the lack of the junior house officer at handover leading to 'signal loss' with respect to sick patients who may not be handed over fully. The process also lacked standardisation and structure compounding the potential loss of information. CONCLUSION: Good handover remains a cornerstone of safe and effective clinical practice and continuity of care. This study has shown how an HFA can be useful in determining problems with the handover process locally. It suggests an approach for improvement and recommends better training at all levels in this aspect of patient care. PMID- 26257905 TI - Improving Compliance with Statins in Patients with Peripheral Arterial Disease: A Quality Improvement Study. AB - Atherosclerosis is an inflammatory disease affecting medium sized arteries. The prevalence, health, and financial impact of the disease has made it a key target for public health and large scale intervention. The statin class of drugs improve morbidity and mortality for patients with peripheral arterial disease (PAD) through polymodal actions. This quality improvement study aimed to determine, and subsequently reduce, the percentage of patients with PAD discharged without statins. According to the Vascular Society of Great Britain and Ireland, and draft National Institute of Health and Clinical Excellence guidance, all patients undergoing major vascular procedures should be prescribed a statin. A baseline audit of patients with PAD under the care of the vascular team at our instituted was undertaken for the period Dec 2009-July 2010. Electronic discharge letters (EDLs) were analysed and compliance with statin prescription were recorded. A number of interventions aimed at improving compliance were then enacted and monitored through weekly PDSA cycles. Junior doctor leadership was key to identifying the problem and conceiving, implementing, and measuring changes. A second cycle was run, using similar data collection methods to the first, for the period August-October 2010. In the first cycle, EDLs pertaining to 113 patient admissions, involving 96 patients with PAD, were examined. Statins were not prescribed in 30.1%. In the second cycle, 86 patient admissions, involving 76 patients, were examined. Statins were not prescribed in 24.4%, representing an 18.9% decrease. Poorly compliant sub-groups included patients presenting with embolism or those for elective angioplasty. PMID- 26257906 TI - Improving Compliance with NICE Guidelines on Parkinson's isease: A Quality Improvement Study. AB - Parkinson's disease can progressively affect daily function and multidisciplinary teamwork is essential to provide high quality care. The National Institute of Health and Clinical Excellence (NICE) issued guidelines regarding diagnosis, follow-up, and multidisciplinary care. This quality improvement project sought to measure and improve the compliance of service provision against the guidelines. In total, 3 audit cycles were completed. Each audit involved reviewing notes of patients attending a Parkinson's disease outpatient clinic against the PD NICE guidelines audit criteria. The first and second audits showed compliance was high for the criteria relating to initial diagnosis and referral but poor for those criteria relating to multidisciplinary referral. A pro forma stamp was recommended to be placed in the notes at each regular Parkinson's outpatient review by a specified date (October 2009), with re-audit occurring in June 2011 as part of the official hospital audit plan. Compliance to the NICE criteria improved to 100% on all criteria measured. However, it was evident from the notes that the pro forma that had been recommended by the previous audit had been in use but was not at present. In fact the pro forma had been so successful that the clinicians had made each of the criteria a routine part of their consultations and so did not need to rely on it. Use of a checklist can have a lasting improvement on compliance with NICE guidelines, even if the intervention itself is transient. PMID- 26257907 TI - Epidemiology and Pathogenesis of C. difficile and MRSA in the Light of Current NHS Control Policies: A Policy review. AB - Healthcare associated infections (HCAIs) cause significant morbidity and mortality, and are estimated to cost the United Kingdom National Health Service L1 billion annually. The current health care infection rates suggest that the level of performance to avoid HCAIs is not maintained consistently. Increasing screening, improving local accountability and performance management, careful use of antibiotics in the management of emergency patients, health economy wide approaches, and improved hand washing will be effective in lowering the rate of HCAIs. This paper reviews current NHS Control Policies in place for Methicillin Resistant Staphylococcus Aureus (MRSA) and C. difficile. PMID- 26257908 TI - NICE Opioids in Palliative Care (Clinical Guideline 140) - A Guideline Summary. PMID- 26257909 TI - Skin Stretching for Burn Scar Excision - A Critically Appraised Topic. AB - Adults with burn scars are a clinical challenge, and the long term sequelae of burns can have a significant impact on the patient. Scar excision is thought to be the best treatment at present, as it results in a smaller scar. Scar stretching has shown promise in a previous study, as it may allow the surgeon to excise more burn scar. The goal of this study was to determine if good evidence exists for the use of burn scar stretching, in routine clinical practice, through the format of a critically appraised topic. A question was formulated using the Patient Intervention Comparator Outcome (PICO) method:-Patient - Adult burn victims-Intervention - Scar excision + skin stretching-Comparator - Scar excision Outcome - Total remaining scar The PICO question was used to develop a search query: "stretch* burn scar" (where '*' represents a wildcard function). A search was then conducted using PubMed, SCOPUS, the Cochrane Library, and Trip Database. One paper was selected for critical appraisal following identification, screening, and eligibility evaluation. The paper was critically appraised using accepted methodology outlined by Straus et al. and reporting quality was assessed using the CONSORT statement for non-pharmacological trials. Areas of methodological or reporting weakness were highlighted. Burn scar stretching, using the device or technique in question, requires much further research before widespread usage in burns patients. PMID- 26257910 TI - Future Directions for Bariatric Surgery in Type 2 Diabetes. PMID- 26257911 TI - Growth, digestive and absorptive capacity and antioxidant status in intestine and hepatopancreas of sub-adult grass carp Ctenopharyngodonidella fed graded levels of dietary threonine. AB - BACKGROUND: This study was carried out to investigate effects of threonine levels on growth, digestive and absorptive capacity and antioxidant status in intestine and hepatopancreas of sub-adult grass carp (Ctenopharyngodonidella). RESULTS: Weight gain, specific growth rate, feed intake and feed efficiency were significantly improved by dietary threonine (P < 0.05). Intestinal activities of trypsin, chymotrypsin, alpha-amylase, lipase, alkaline phosphatase, gamma glutamyl transpeptidase and creatine kinase took the similar trends. Contents of malondialdehyde and protein carbonyl in intestine and hepatopancreas were significantly decreased by dietary optimal threonine supplementation (P < 0.05). Anti-superoxide anion capacity, anti-hydroxyl radical capacity, glutathione content and activities of superoxide dismutase, catalase and glutathione-S transferase in intestine and hepatopancreas were enhanced by dietary threonine (P < 0.05). CONCLUSIONS: Dietary threonine could improve growth, enhance digestive and absorptive capacity and antioxidant status in intestine and hepatopancreas of sub-adult grass carp. The dietary threonine requirement of sub-adult grass carp (441.9-1,013.4 g) based on weight gain was 11.6 g/kg diet or 41.5 g/kg of dietary protein by quadratic regression analysis. PMID- 26257913 TI - Incorporation of quantum dots in silk biomaterials for fluorescence imaging. AB - Tracking the distribution and degradation of biomaterials after in vivo implantation or injection is important for tissue engineering and drug delivery. Intrinsic and externally labeled fluorescence has been widely used for these purposes. In the present study, 3-mercaptopropionic acid (MPA)-coated CdTe quantum dots (QDs) were incorporated into silk materials via strong interactions between QDs and silk, likely involving the hydrophobic beta-sheet structures in silk. MPA-QDs were pre-mixed with silk solution, followed by ultrasonication to induce silk gelation or by blending with polyvinyl alcohol (PVA) to generate silk microspheres. Silk structural changes and hydrogel/microsphere morphologies were examined by ATR-FTIR and SEM, respectively. The fluorescence of QDs-incorporated silk hydrogels and microspheres remained stable in PBS pH 7.4 for more than 4 days. The amount of QDs released from the materials during the incubation was dependent on loading; no QDs were released when loading was below 0.026 nmol/mg silk. After subcutaneous injection in mice, the fluorescence of QDs-incorporated silk microspheres was quenched within 24 h, similar to that of free QDs. In contrast, the QDs-incorporated silk hydrogels fluoresced for more than 4 days in vivo. PMID- 26257912 TI - Histamine-functionalized copolymer micelles as a drug delivery system in 2D and 3D models of breast cancer. AB - Histamine functionalized block copolymers based on poly(allyl glycidyl ether)-b poly(ethylene oxide) (PAGE-b-PEO) were prepared with different ratios of histamine and octyl or benzyl groups using UV-initiated thiol-ene click chemistry. At neutral pH, the histamine units are uncharged and hydrophobic, while in acidic environments, such as in the endosome, lysosomes, or extracellular sites of tumours, the histamine groups are positively charged and hydrophilic. pH responsible polymer drug delivery systems is a promising route to site specific delivery of drugs and offers the potential to avoid side effects of systemic treatment. Our detailed in vitro experiments of the efficacy of drug delivery and the intracellular localization characteristics of this library of NPs in 2D and 3D cultures of breast cancer revealed that the 50% histamine modified polymer loaded with DOX exhibited rapid accumulation in the nucleus of free DOX within 2 h. Confocal studies showed enhanced mitochondrial localization and lysosomal escape when compared to controls. From these combined studies, it was shown that by accurately tuning the structure of the initial block copolymers, the resulting self-assembled NPs can be designed to exploit histamine as an endosomal escape trigger and the octyl/benzyl units give rise to a hydrophobic core resulting in highly efficacious drug delivery systems (DDS) with control over intracellular localization. Optimization and rational control of the intracellular localization of both DDS and the parent drug can give nanomedicines a substantial increase in efficacy and should be explored in future studies. PMID- 26257914 TI - Faecal Escherichia coli isolates show potential to cause endogenous infection in patients admitted to the ICU in a tertiary care hospital. AB - Nosocomial infections are acquired during hospital treatment or in a hospital environment. One such infecting agent, Escherichia coli, harbours many virulence genes that enable it to become pathogenic, causing damage to the host. The mechanism of the E. coli virulence factors provenance to cause infection in host environments is not clearly elucidated. We investigated the virulence and pathogenicity of E. coli affected by the host environment. For this, blood (n = 78) and faecal (n = 83) E. coli isolates were collected from patients with and without sepsis, respectively, who had been admitted to the intensive care unit. The E. coli genomic DNA was isolated; the phylogenetic grouping was conducted by triplex PCR. The occurrence of nine virulence genes among the all the isolates was confirmed by gene-specific PCR. The prevalence of E. coli in blood isolates was more in phylogenetic groups B2 and D compared to groups A and B1. However, in faecal isolates, there was no significant difference. The prevalence of adhesin and toxin (papG, sfa, afa, cnf1, hlyA) genes was higher in blood compared to faecal E. coli isolates. However, the prevalence of aer, traT and PAI was similar as well as higher among both of these groups. These observations indicate a role of external environment (hospital setting) on host susceptibility (development of infection) in the faecal E. coli isolates, thereby making the patient prone to a sepsis condition. PMID- 26257915 TI - MUS-2, a novel variant of the chromosome-encoded beta-lactamase MUS-1, from Myroides odoratimimus. AB - The aim of the present study was to investigate the molecular mechanism of carbapenem resistance of three imipenem-resistant isolates of Myroides odoratimimus recovered from two livestock farms of cows and pigeons by rectal swab in Lebanon in January 2014. Investigation of imipenem resistance of these isolates using the modified Hodge test, the EDTA test, the modified CarbaNP test and the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry Ultraflex assay showed a carbapenemase activity due to the presence of a chromosome-encoded beta-lactamase MUS, verified by PCR. However amplification and sequencing of this chromosomal gene showed a novel variant of it designated MUS-2 by the curators of the Lahey database of beta-lactamases (http://www.lahey.org/Studies/webt.asp). Cloning of the bla MUS-2 was performed, followed by protein expression in Escherichia coli TOP 10. Pulsed-field gel electrophoresis clearly showed that the three isolates belonged to the same clone. This study reports a novel variant of the chromosome-encoded bla MUS-1 associated with carbapenem resistance in Myroides odoratimimus and shows that animals may represent a reservoir of bacteria harbouring several variants of resistance genes. PMID- 26257916 TI - Synthetic Strategies Toward the Decalin Motif of Maklamicin and Related Spirotetronates. AB - Herein we describe a scalable approach to the decalin moiety of maklamicin. Key to the synthesis is an intramolecular Diels-Alder (IMDA) reaction that proceeds via an endo-axial transition state to generate the desired stereochemistry. We explored the diastereoselectivity of the IMDA reaction as a function of both chiral catalysis and acyclic precursor stereochemistry. PMID- 26257918 TI - Evaluation of ciprofloxacin and metronidazole encapsulated biomimetic nanomatrix gel on Enterococcus faecalis and Treponema denticola. AB - BACKGROUND: A triple antibiotic mixture (ciprofloxacin; CF, metronidazole; MN, and minocycline; MC) has been used for dental root canal medicaments in pulp regeneration therapy. However, tooth discolorations, cervical root fractures, and inadequate pulp-dentin formation have been reported due to the triple antibiotic regimen. Therefore, an antibiotic encapsulated biomimetic nanomatrix gel was developed to minimize the clinical limitations and maximize a natural healing process in root canal infections. In this study, minimal bacterial concentrations (MBC) of the selected antibiotics (CF and MN) were tested in 14 representative endodontic bacterial species. Then MBC of each CF and MN were separately encapsulated within the injectable self-assembled biomimetic nanomatrix gel to evaluate antibacterial level on Enterococcus faecalis and Treponema denticola. RESULTS: Antibiotic concentrations lower than 0.2 ug/mL of CF and MN demonstrated antibacterial activity on the 14 endodontic species. Furthermore, 6 different concentrations of CF and MN separately encapsulated with the injectable self assembled biomimetic nanomatrix gel demonstrated antibacterial activity on Enterococcus faecalis and Treponema denticola at the lowest tested concentration of 0.0625 ug/mL. CONCLUSIONS: These results suggest that each CF and MN encapsulated within the injectable self-assembled biomimetic nanomatrix gel demonstrated antibacterial effects, which could be effective for the root canal disinfection while eliminating MC. In the long term, the antibiotic encapsulated injectable self-assembled biomimetic nanomatrix gel can provide a multifunctional antibiotic delivery method with potential root regeneration. Further studies are currently underway to evaluate the effects of combined CF and MN encapsulated within the injectable self-assembled biomimetic nanomatrix gel on clinical samples. PMID- 26257917 TI - An ongoing search for potential targets and therapies for lethal sepsis. AB - Sepsis, which refers to a systemic inflammatory response syndrome resulting from a microbial infection, represents the leading cause of death in intensive care units. The pathogenesis of sepsis remains poorly understood although it is attributable to dysregulated immune responses orchestrated by innate immune cells that are sequentially released early (e.g., tumor necrosis factor(TNF), interleukin-1(IL-1), and interferon-gamma(IFN-gamma)) and late (e.g., high mobility group box 1(HMGB1)) pro-inflammatory mediators. As a ubiquitous nuclear protein, HMGB1 can be passively released from pathologically damaged cells, thereby converging infection and injury on commonly dysregulated inflammatory responses. We review evidence that supports extracellular HMGB1 as a late mediator of inflammatory diseases and discuss the potential of several Chinese herbal components as HMGB1-targeting therapies. We propose that it is important to develop strategies for specifically attenuating injury-elicited inflammatory responses without compromising the infection-mediated innate immunity for the clinical management of sepsis and other inflammatory diseases. PMID- 26257919 TI - Boceprevir-Based Triple Antiviral Therapy for Chronic Hepatitis C Virus Infection in Kidney-Transplant Candidates. AB - Background. There are few data on the combination of (pegylated-) interferon- (Peg-IFN-) alpha, ribavirin, and first-generation direct-acting antiviral agents (DAAs). Our aim was to describe the efficacy and safety of Peg-IFN-alpha, ribavirin, and boceprevir in hemodialysis patients. Patients. Six hemodialysis patients, chronically infected by genotype-1 HCV, were given Peg-IFN-alpha (135 ug/week), ribavirin (200 mg/d), and boceprevir (2400 mg/d) for 48 weeks. Results. At initiation of antiviral therapy, median viral concentration was 5.68 (3.78 6.55) log IU/mL. HCV RNA was undetectable in four of the six patients at week 4 and in all patients at week 24. A breakthrough was observed in two patients between weeks 24 and 48, and a third patient stopped antiviral therapy between weeks 24 and 48 because of severe peripheral neuropathy. At week 48, HCV RNA was undetectable in three patients. Of these, two patients relapsed within a month after antiviral therapy was stopped. Hence, only one patient had a sustained virological response; he was a previous partial responder. Overall, anemia was the main side effect. Conclusion. A triple antiviral therapy based on Peg-IFN alpha, ribavirin, and boceprevir is not optimal at treating hemodialysis patients with chronic HCV infection. Studies using new-generation drugs are required in this setting. PMID- 26257920 TI - Factors Associated with Uncontrolled Hypertension among Renal Transplant Recipients Attending Nephrology Clinics in Nairobi, Kenya. AB - Objective. To determine the factors associated with poor blood pressure control among renal transplant recipients in a resource-limited setting. Methods. A cross sectional study was carried out on renal transplant recipients at the Kenyatta National Hospital. Sociodemographic details, blood pressure, urine albumin : creatinine ratio, and adherence using the MMAS-8 questionnaire were noted. Independent factors associated with uncontrolled hypertension were determined using logistic regression analysis. Results. 85 subjects were evaluated. Mean age was 42.4 (SD +/- 12.2) years, with a male : female ratio of 1.9 : 1. Fifty-five patients (64.7%) had uncontrolled hypertension (BP >= 130/80 mmHg). On univariate analysis, male sex (OR 3.7, 95% CI 1.4-9.5, p = 0.006), higher levels of proteinuria (p = 0.042), and nonadherence to antihypertensives (OR 18, 95% CI 5.2 65.7, p < 0.001) were associated with uncontrolled hypertension. On logistic regression analysis, male sex (adjusted OR 4.6, 95% CI 1.1-19.0, p = 0.034) and nonadherence (adjusted OR 33.8, 95% CI 8.6-73.0, p < 0.001) were independently associated with uncontrolled hypertension. Conclusion. Factors associated with poor blood pressure control in this cohort were male sex and nonadherence to antihypertensives. Emphasis on adherence to antihypertensive therapy must be pursued within this population. PMID- 26257921 TI - Extraction of Iron from the Rabbit Anterior Chamber with Reverse Iontophoresis. AB - Ocular siderosis is a common eye disease caused by retention of an iron containing intraocular foreign body in the eye. Iron-containing intraocular foreign bodies may cause severe inflammatory reaction and affect visual function. Currently the optimal treatment method of ocular siderosis is a moot point. This study used the reverse iontophoresis technique to noninvasively extract iron from the rabbit anterior chamber. By slit lamp observation and histological examination, reverse iontophoresis treatment has a good effect on ocular siderosis. Reverse iontophoresis seems to be a noninvasive and promising approach to extract iron from the anterior chamber to treat ocular siderosis. PMID- 26257923 TI - Functionalized formazans: A review on recent progress in their pharmacological activities. AB - This review provides an up to date information about the diverse pharmaceutical activities of formazans. The bibliography includes 97 references which have been published during the period from 1980 to 2013. The covered biological activities of the title compounds include antioxidant, anticonvulsant, therapeutic, anthelmintic, anti-tubercular, antiviral, anti-inflammatory, anticancer, anti HIV, antimicrobial, antiparkinsonian, cardiovascular and antiproliferative activities. PMID- 26257924 TI - Why the radiation-attenuated cercarial immunization studies failed to guide the road for an effective schistosomiasis vaccine: A review. AB - Schistosomiasis is a debilitating parasitic disease caused by platyhelminthes of the genus Schistosoma, notably Schistosoma mansoni, Schistosoma haematobium, and Schistosoma japonicum. Pioneer researchers used radiation-attenuated (RA) schistosome larvae to immunize laboratory rodent and non-human primate hosts. Significant and reproducible reduction in challenge worm burden varying from 30% to 90% was achieved, providing a sound proof that vaccination against this infection is feasible. Extensive histopathological, tissue mincing and incubation, autoradiographic tracking, parasitological, and immunological studies led to defining conditions and settings for achieving optimal protection and delineating the resistance underlying mechanisms. The present review aims to summarize these findings and draw the lessons that should have guided the development of an effective schistosomiasis vaccine. PMID- 26257925 TI - Assessing the global phylum level diversity within the bacterial domain: A review. AB - Microbial ecology is the study of microbes in the natural environment and their interactions with each other. Investigating the nature of microorganisms residing within a specific habitat is an extremely important component of microbial ecology. Such microbial diversity surveys aim to determine the identity, physiological preferences, metabolic capabilities, and genomic features of microbial taxa within a specific ecosystem. A comprehensive review of various aspects of microbial diversity (phylogenetic, functional, and genomic diversities) in the microbial (bacterial, archaeal, and microeukaryotic) world is clearly a daunting task that could not be aptly summarized in a single review. Here, we focus on one aspect of diversity (phylogenetic diversity) in one microbial domain (the Bacteria). We restrict our analysis to the highest taxonomic rank (phylum) and attempt to investigate the extent of global phylum level diversity within the Bacteria. We present a brief historical perspective on the subject and highlight how the adaptation of molecular biological and phylogenetic approaches has greatly expanded our view of global bacterial diversity. We also summarize recent progress toward the discovery of novel bacterial phyla, present evidences that the scope of phylum level diversity in nature has hardly been exhausted, and propose novel approaches that could greatly facilitate the discovery process of novel bacterial phyla within various ecosystems. PMID- 26257927 TI - New era for management of chronic hepatitis C virus using direct antiviral agents: A review. AB - The pegylated interferon regimen has long been the lone effective management of chronic hepatitis C with modest response. The first appearance of protease inhibitors included boceprevir and telaprevir. However, their efficacy was limited to genotype 1. Recently, direct antiviral agents opened the gate for a real effective management of HCV, certainly after FDA approval of some compounds that further paved the way for the appearance of enormous potent direct antiviral agents that may achieve successful eradication of HCV. PMID- 26257926 TI - Emerging flavobacterial infections in fish: A review. AB - Flavobacterial diseases in fish are caused by multiple bacterial species within the family Flavobacteriaceae and are responsible for devastating losses in wild and farmed fish stocks around the world. In addition to directly imposing negative economic and ecological effects, flavobacterial disease outbreaks are also notoriously difficult to prevent and control despite nearly 100 years of scientific research. The emergence of recent reports linking previously uncharacterized flavobacteria to systemic infections and mortality events in fish stocks of Europe, South America, Asia, Africa, and North America is also of major concern and has highlighted some of the difficulties surrounding the diagnosis and chemotherapeutic treatment of flavobacterial fish diseases. Herein, we provide a review of the literature that focuses on Flavobacterium and Chryseobacterium spp. and emphasizes those associated with fish. PMID- 26257928 TI - Laser researches on livestock semen and oocytes: A brief review. AB - This article presents a brief review of the past and present literature pertinent to laser effects on sperm motility parameters, improvement of oocyte maturation and characterization of semen in livestock. The aim was, on one hand, to make the readers aware of such knowledge and on the other hand to trigger the interest of the animal reproduction scientific community in attempting some laser techniques that have not yet been fully exploited in the field of artificial insemination. With respect to the conventional methods, laser is a more sensitive and less costly technology that can be used for improving artificial insemination and embryo production system. Since 1980s, laser treatment came on the biological samples scene; its applications have continuously been developed thereafter. Exploitation of laser light by various researchers for improving the reproductive efficiency of sperm cells and the maturation rate in different livestock is demonstrated herein. Laser irradiation, in principal, can increase the production of adenosine triphosphate (ATP) and consequently increases the energy provided to the cell. Since sperm motility and oocyte maturation depend on the energy consumption, an increase in the energy supply to the cells will be of great importance. In addition, the authors also discuss the use of laser spectrochemical analytical techniques, such as laser induced breakdown spectroscopy (LIBS) and laser induced fluorescence (LIF), in characterization of semen samples. PMID- 26257929 TI - Mesothelioma treatment: Are we on target? A review. AB - Targeted treatment is a therapy directed at a specific molecular target close to a hallmark of cancer. The target should be measurable with a biomarker and measurement of the target should correlate with clinical outcome when targeted treatment is administered. Current clinical guidelines do not recommend targeted or biological therapy in MPM. However, since these recommendations came out, new agents have been investigated in MPM. This review updates the use of targeted and biological treatment in patients with mesothelioma. PMID- 26257931 TI - GnRH agonist for final oocyte maturation in GnRH antagonist co-treated IVF/ICSI treatment cycles: Systematic review and meta-analysis. AB - Final oocyte maturation in GnRH antagonist co-treated IVF/ICSI cycles can be triggered with HCG or a GnRH agonist. We conducted a systematic review and meta analysis of randomized controlled trials to evaluate the efficacy and safety of the final oocyte maturation trigger in GnRH antagonist co-treated cycles. Outcome measures were ongoing pregnancy rate (OPR) and ovarian hyperstimulation syndrome (OHSS) incidence. Searches: were conducted in MEDLINE, EMBASE, Science Direct, Cochrane Library, and databases of abstracts. There was a statistically significant difference against the GnRH agonist for OPR in fresh autologous cycles (n = 1024) with an odd ratio (OR) of 0.69 (95% CI: 0.52-0.93). In oocyte donor cycles (n = 342) there was no evidence of a difference (OR: 0.91; 95% CI: 0.59-1.40). There was a statistically significant difference in favour of GnRH agonist regarding the incidence of OHSS in fresh autologous cycles (OR: 0.06; 95% CI: 0.01-0.33) and donor cycles respectively (OR: 0.06; 95% CI: 0.01-0.27). In conclusion GnRH agonist trigger for final oocyte maturation trigger in GnRH antagonist cycles is safer but less efficient than HCG. PMID- 26257930 TI - Brain stem adenosine receptors modulate centrally mediated hypotensive responses in conscious rats: A review. AB - Adenosine is implicated in the modulation of cardiovascular responses either at the peripheral or at central level in experimental animals. However, there are no dedicated reviews on the involvement of adenosine in mediating the hypotensive response of centrally administered clonidine in general and specifically in aortically barodenervated rats (ABD). The conscious ABD rat model exhibits surgically induced baroreflex dysfunction and exaggerated hypotensive response, compared with conscious sham-operated (SO) rats. The current review focuses on, the role of adenosine receptors in blood pressure (BP) regulation and their possible crosstalk with other receptors e.g. imidazoline (I1) and alpha (alpha2A) adrenergic receptor (AR). The former receptor is a molecular target for clonidine, whose hypotensive effect is enhanced approx. 3-fold in conscious ABD rats. We also discussed how the balance between the brain stem adenosine A1 and A2A receptors is regulated by baroreceptors and how such balance influences the centrally mediated hypotensive responses. The use of the ABD rat model yielded insight into the downstream signaling cascades following clonidine-evoked hypotension in a surgical model of baroreflex dysfunction. PMID- 26257932 TI - Physical and cognitive consequences of fatigue: A review. AB - Fatigue is a common worrying complaint among people performing physical activities on the basis of training or rehabilitation. An enormous amount of research articles have been published on the topic of fatigue and its effect on physical and physiological functions. The goal of this review was to focus on the effect of fatigue on muscle activity, proprioception, and cognitive functions and to summarize the results to understand the influence of fatigue on these functions. Attaining this goal provides evidence and guidance when dealing with patients and/or healthy individuals in performing maximal or submaximal exercises. PMID- 26257933 TI - Some subgroup embeddings in finite groups: A mini review. AB - In this survey paper several subgroup embedding properties related to some types of permutability are introduced and studied. PMID- 26257934 TI - A mini-review on Biginelli adducts with notable pharmacological properties. AB - Since the disclosure of Biginelli reaction by the chemist Pietro Biginelli, functionalized 3,4-dihydropyrimidin-2(1H)-ones/thiones (DHPMs) have emerged as prototypes for the design of compounds with a broad variety of biological activities. This mini-review describes over 100 Biginelli adducts demonstrated to be promising anticancer, inhibitors of calcium channel, anti-inflammatory, antimicrobial and antioxidant agents. Thus, this compilation presents the most notable in vitro and in vivo results for such fascinating class of organic compounds. PMID- 26257935 TI - A mini review on cancer of unknown primary site: A clinical puzzle for the oncologists. AB - Cancer of unknown primary (CUP) is a well recognized clinical syndrome, accounting for 3-5% of all malignancies. It is characterized as a disease with an early dissemination of metastases without a primary detected site after extensive laboratory and clinical investigations. CUP is divided into the favorable and unfavorable groups based on histopathological and clinical manifestations. Adenocarcinoma of various differentiations is the commonest histopathological subtype. Favorable groups are treated with local or systemic treatment and some of them are enjoying long-term survival. On the contrary, unfavorable groups are treated with empirical chemotherapy having usually a dismal prognosis. Gene profiling microarray diagnosis has a high diagnostic sensitivity, but its predictive or prognostic value remains uncertain. PMID- 26257937 TI - Legendre spectral-collocation method for solving some types of fractional optimal control problems. AB - In this paper, the Legendre spectral-collocation method was applied to obtain approximate solutions for some types of fractional optimal control problems (FOCPs). The fractional derivative was described in the Caputo sense. Two different approaches were presented, in the first approach, necessary optimality conditions in terms of the associated Hamiltonian were approximated. In the second approach, the state equation was discretized first using the trapezoidal rule for the numerical integration followed by the Rayleigh-Ritz method to evaluate both the state and control variables. Illustrative examples were included to demonstrate the validity and applicability of the proposed techniques. PMID- 26257936 TI - Possible drug-drug interaction in dogs and cats resulted from alteration in drug metabolism: A mini review. AB - Pharmacokinetic drug-drug interactions (in particular at metabolism) may result in fatal adverse effects in some cases. This basic information, therefore, is needed for drug therapy even in veterinary medicine, as multidrug therapy is not rare in canines and felines. The aim of this review was focused on possible drug drug interactions in dogs and cats. The interaction includes enzyme induction by phenobarbital, enzyme inhibition by ketoconazole and fluoroquinolones, and down regulation of enzymes by dexamethasone. A final conclusion based upon the available literatures and author's experience is given at the end of the review. PMID- 26257938 TI - Individual and competitive adsorption of phenol and nickel onto multiwalled carbon nanotubes. AB - Individual and competitive adsorption studies were carried out to investigate the removal of phenol and nickel ions by adsorption onto multiwalled carbon nanotubes (MWCNTs). The carbon nanotubes were characterized by different techniques such as X-ray diffraction, scanning electron microscopy, thermal analysis and Fourier transformation infrared spectroscopy. The different experimental conditions affecting the adsorption process were investigated. Kinetics and equilibrium models were tested for fitting the adsorption experimental data. The characterization experimental results proved that the studied adsorbent possess different surface functional groups as well as typical morphological features. The batch experiments revealed that 300 min of contact time was enough to achieve equilibrium for the adsorption of both phenol and nickel at an initial adsorbate concentration of 25 mg/l, an adsorbent dosage of 5 g/l, and a solution pH of 7. The adsorption of phenol and nickel by MWCNTs followed the pseudo-second order kinetic model and the intraparticle diffusion model was quite good in describing the adsorption mechanism. The Langmuir equilibrium model fitted well the experimental data indicating the homogeneity of the adsorbent surface sites. The maximum Langmuir adsorption capacities were found to be 32.23 and 6.09 mg/g, for phenol and Ni ions, respectively. The removal efficiency of MWCNTs for nickel ions or phenol in real wastewater samples at the optimum conditions reached up to 60% and 70%, respectively. PMID- 26257939 TI - A performance-oriented power transformer design methodology using multi-objective evolutionary optimization. AB - Transformers are regarded as crucial components in power systems. Due to market globalization, power transformer manufacturers are facing an increasingly competitive environment that mandates the adoption of design strategies yielding better performance at lower costs. In this paper, a power transformer design methodology using multi-objective evolutionary optimization is proposed. Using this methodology, which is tailored to be target performance design-oriented, quick rough estimation of transformer design specifics may be inferred. Testing of the suggested approach revealed significant qualitative and quantitative match with measured design and performance values. Details of the proposed methodology as well as sample design results are reported in the paper. PMID- 26257940 TI - Diffusive smoothing of 3D segmented medical data. AB - This paper proposes an accurate, computationally efficient, and spectrum-free formulation of the heat diffusion smoothing on 3D shapes, represented as triangle meshes. The idea behind our approach is to apply a [Formula: see text]-degree Pade-Chebyshev rational approximation to the solution of the heat diffusion equation. The proposed formulation is equivalent to solve r sparse, symmetric linear systems, is free of user-defined parameters, and is robust to surface discretization. We also discuss a simple criterion to select the time parameter that provides the best compromise between approximation accuracy and smoothness of the solution. Finally, our experiments on anatomical data show that the spectrum-free approach greatly reduces the computational cost and guarantees a higher approximation accuracy than previous work. PMID- 26257941 TI - Regional view of a Trans-African Drainage System. AB - Despite the arid to hyperarid climate of the Great Sahara of North Africa, pluvial climates dominated the region. Radar data shed some light on the postulated Trans-African Drainage System and its relationship to active and inactive tributaries of the Nile basin. Interpretations of recent elevation data confirm a source of the river water from the Red Sea highlands did not connect the Atlantic Ocean across Tushka basin, highlands of Uwinate and Darfur, and Chad basin, but northward to the ancestral Nile Delta. Elements of topography and climate were considered. They show that the former segments of the Nile closely mirror present-day tributaries of the Nile basin in drainage geometry, landscape, and climate. A rainfall data interpolation scenario revealed that this basin received concurrent runoff from both flanks such as Gabgaba-Allaqi to the east and Tushka basin to the west, similar to present-day Sobat and White Nile tributaries, respectively. Overall the western tributaries such as those of Tushka basin and Howar lead to the Nile, which was (and still is) the biggest river system in Africa. PMID- 26257942 TI - Porous polymer monolithic columns with gold nanoparticles as an intermediate ligand for the separation of proteins in reverse phase-ion exchange mixed mode. AB - A new approach has been developed for the preparation of mixed-mode stationary phases to separate proteins. The pore surface of monolithic poly(glycidyl methacrylate-co-ethylene dimethacrylate) capillary columns was functionalized with thiols and coated with gold nanoparticles. The final mixed mode surface chemistry was formed by attaching, in a single step, alkanethiols, mercaptoalkanoic acids, and their mixtures on the free surface of attached gold nanoparticles. Use of these mixtures allowed fine tuning of the hydrophobic/hydrophilic balance. The amount of attached gold nanoparticles according to thermal gravimetric analysis was 44.8 wt.%. This value together with results of frontal elution enabled calculation of surface coverage with the alkanethiol and mercaptoalkanoic acid ligands. Interestingly, alkanethiols coverage in a range of 4.46-4.51 molecules/nm(2) significantly exceeded that of mercaptoalkanoic acids with 2.39-2.45 molecules/nm(2). The mixed mode character of these monolithic stationary phases was for the first time demonstrated in the separations of proteins that could be achieved in the same column using gradient elution conditions typical of reverse phase (using gradient of acetonitrile in water) and ion exchange chromatographic modes (applying gradient of salt in water), respectively. PMID- 26257943 TI - Allogeneic hematopoietic stem cell transplantation for non-malignant hematological disorders. AB - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) from a geno identical matched sibling (MSD) is one of the most successful therapies in patients with non-malignant hematological disorders. This study included 273 patients with severe aplastic anemia (SAA), 152 patients with B-Thalassemia major (BTM), 31 patients with Fanconi's anemia (FA), 20 patients with congenital immunodeficiency diseases (ID), and 13 patients with inherited metabolic disorders (IMD) allografted from a MSD. In SAA, the 8-year overall survival (OS) of the whole group patients was 74%. OS was significantly better in patients conditioned with fludarabine and cyclophosphamide (Flu/Cy) than in those who received cyclophosphamide and antithymocyte globulin (Cy/ATG) (p = 0.021). Acute graft-versus-host disease (aGVHD) grade II-IV occurred in 15% while chronic GVHD (cGVHD) occurred in 28%. In BTM, the 12-year disease-free survival (DFS) of the whole group of BTM patients was 72.4%. DFS was 74% for peripheral blood stem cell (PBSC) group compared to 64% in the BM stem cell group. The incidence of graft rejection was significantly lower in patients who received PBSC than in those who received BM (9% vs 25%) (p = 0.036). AGVHD grade II-IV and cGVHD occurred in 15% and 12% of the whole group of BTM patients respectively. In FA, the 5-year OS was 64.5%. Graft rejection occurred in 10% of patients. Grade II-IV aGVHD occurred in 16% while cGVHD occurred in 4%. In ID, the 5-year OS was 62%. Graft rejection occurred in two (10%) patients. Three patients (15%) developed grade II-IV aGVHD, 2 of them progressed to secondary cGVHD. In IMD, OS was 46% at 5 years. Graft rejection occurred in 8% of patients. AGVHD grade II-IV occurred in 15% while cGVHD occurred in 14%. In conclusion, Allo-HSCT provides a higher DFS rate over conventional therapies for patients with non-malignant hematological disorders with prolonged survival. PMID- 26257944 TI - Dynamic potential and surface morphology study of sertraline membrane sensors. AB - New rapid, sensitive and simple electrometric method was developed to determine sertraline hydrochloride (Ser-Cl) in its pure raw material and pharmaceutical formulations. Membrane sensors based on heteropolyacids as ion associating material were prepared. Silicomolybdic acid (SMA), silicotungstic acid (STA) and phosphomolybdic acid (PMA) were used. The slope and limit of detection are 50.00, 60.00 and 53.24 mV/decade and 2.51, 5.62 and 4.85 MUmol L(-1) for Ser-ST, Ser-PM and Ser-SM membrane sensors, respectively. Linear range is 0.01-10.00 for the three sensors. These new sensors were used for the potentiometric titration of Ser-Cl using sodium tetraphenylborate as titrant. The surface morphologies of the prepared membranes with and without the modifier (ion-associate) were studied using scanning and atomic force microscopes. PMID- 26257945 TI - Effect of preheating of low shrinking resin composite on intrapulpal temperature and microtensile bond strength to dentin. AB - The effect of preheating of the silorane-based resin composite on intrapulpal temperature (IPT) and dentin microtensile bond strength (MUTBS) was evaluated. For the IPT, teeth (n = 15) were sectioned to obtain discs of 0.5 mm thickness (2 discs/tooth). The discs were divided into three groups (n = 10/group) according to the temperature of the Filtek LSTM silorane-based resin composite during its placement, either at room temperature (23 +/- 1 degrees C) or preheated to 54 degrees C or 68 degrees C using a commercial CalsetTM device. Discs were subjected to a simulated intrapulpal pressure (IPP) and placed inside a specially constructed incubator adjusted at 37 degrees C. IPT was measured before, during and after placement and curing of the resin composite using K-type thermocouple. For MUTBS testing, flat occlusal middentin surfaces (n = 24) were obtained. P90 System Adhesive was applied according to manufacturer's instructions then Filtek LS was placed at the tested temperatures (n = 6). Restorative procedures were done while the specimens were connected to IPP simulation. IPP was maintained and the specimens were immersed in artificial saliva at 37 degrees C for 24 h before testing. Each specimen was sectioned into sticks (0.9 +/- 0.01 mm(2)). The sticks (24/group) were subjected to MUTBS test and their modes of failure were determined using scanning electron microscope (SEM). For both preheated groups, IPT increased equally by 1.5-2 degrees C upon application of the composite. After light curing, IPT increased by 4-5 degrees C in all tested groups. Nevertheless, the IPT of the preheated groups required a longer time to return to the baseline temperature. One-way ANOVA revealed no significant difference between the MUTBS values of all groups. SEM revealed predominately mixed mode of failure. Preheating of silorane-based resin composite increased the IPT but not to the critical level and had no effect on dentin MUTBS. PMID- 26257946 TI - Task based synthesis of serial manipulators. AB - Computing the optimal geometric structure of manipulators is one of the most intricate problems in contemporary robot kinematics. Robotic manipulators are designed and built to perform certain predetermined tasks. There is a very close relationship between the structure of the manipulator and its kinematic performance. It is therefore important to incorporate such task requirements during the design and synthesis of the robotic manipulators. Such task requirements and performance constraints can be specified in terms of the required end-effector positions, orientations and velocities along the task trajectory. In this work, we present a comprehensive method to develop the optimal geometric structure (DH parameters) of a non-redundant six degree of freedom serial manipulator from task descriptions. In this work we define, develop and test a methodology to design optimal manipulator configurations based on task descriptions. This methodology is devised to investigate all possible manipulator configurations that can satisfy the task performance requirements under imposed joint constraints. Out of all the possible structures, the structures that can reach all the task points with the required orientations are selected. Next, these candidate structures are tested to see whether they can attain end-effector velocities in arbitrary directions within the user defined joint constraints, so that they can deliver the best kinematic performance. Additionally least power consuming configurations are also identified. PMID- 26257947 TI - The effects of different night-time temperatures and cultivation durations on the polyphenolic contents of lettuce: Application of principal component analysis. AB - The present study was conducted to characterize the polyphenolic contents of lettuce leaves grown under different night-time temperatures (4, 12, and 20 degrees C) and cultivation durations (5, 15, and 20 days) using high performance liquid chromatography-tandem mass spectrometry (LC/MS/MS). The assay method was validated based on specificity, linearity, accuracy, precision, and the performance limit. The total polyphenolic contents were highest (2462.6 mg/kg) after transplantation at a night temperature of 20 degrees C on day 20 and lowest (1132.7 mg/kg) at the same temperature on day 5. Quantification and principal component analysis showed that the relative contents of quercetin and kaempferol were markedly higher during the early stage of cultivation (day 5) than those of day 15 and 20, and that night-time temperatures of 12 and 20 degrees C on day 20 were favorable for producing polyphenol-rich lettuce containing caffeic acid. In conclusion, a synergistic effect between high night time temperatures (12 and 20 degrees C) and cultivation duration (20 days) produced lettuce rich in polyphenols compared to that at low temperature (4 degrees C). PMID- 26257948 TI - Efficacy of pH elevation as a bactericidal strategy for treating ballast water of freight carriers. AB - Treatment of ship ballast water with sodium hydroxide (NaOH) is one method currently being developed to minimize the risk to introduce aquatic invasive species. The bactericidal capability of sodium hydroxide was determined for 148 bacterial strains from ballast water collected in 2009 and 2010 from the M/V Indiana Harbor, a bulk-freight carrier plying the Laurentian Great Lakes, USA. Primary culture of bacteria was done using brain heart infusion agar and a developmental medium. Strains were characterized based on PCR amplification and sequencing of a portion of the 16S rRNA gene. Sequence similarities (99+ %) were determined by comparison with the National Center for Biotechnology Information (NCBI) GenBank catalog. Flavobacterium spp. were the most prevalent bacteria characterized in 2009, comprising 51.1% (24/47) of the total, and Pseudomonas spp. (62/101; 61.4%) and Brevundimonas spp. (22/101; 21.8%) were the predominate bacteria recovered in 2010; together, comprising 83.2% (84/101) of the total. Testing was done in tryptic soy broth (TSB) medium adjusted with 5 N NaOH. Growth of each strain was evaluated at pH 10.0, pH 11.0 and pH 12.0, and 4 h up to 72 h. The median cell count at 0 h for 148 cultures was 5.20 * 10(6) cfu/mL with a range 1.02 * 10(5)-1.60 * 10(8) cfu/mL. The TSB adjusted to pH 10.0 and incubation for less than 24 h was bactericidal to 52 (35.1%) strains. Growth in pH 11.0 TSB for less than 4 h was bactericidal to 131 (88.5%) strains and pH 11.0 within 12 h was bactericidal to 141 (95.3%). One strain, Bacillus horikoshii, survived the harshest treatment, pH 12.0 for 72 h. PMID- 26257949 TI - Residue analysis of orthosulfamuron herbicide in fatty rice using liquid chromatography-tandem mass spectrometry. AB - In the present study, orthosulfamuron residues were extracted from fatty (unpolished) rice and rice straw using a modified QuEChERS method and analyzed using liquid chromatography-tandem mass spectrometry. The matrix-matched calibration was linear over the concentration ranges of 0.01-2.0 mg/kg with determination coefficient (R (2)) ? 0.997. The recovery rates at two fortification levels (0.1 and 0.5 mg/kg) were satisfactory and ranged between 88.1% and 100.6%, with relative standard deviation (RSD) <8%. The limit of quantitation, 0.03 mg/kg, was lower than the maximum residue limit, 0.05 mg/kg, set by the Ministry of Food and Drug Safety in the Republic of Korea. The developed method was applied successfully to field samples harvested at 116 days and none of the samples were positive for the residue. PMID- 26257950 TI - An unusual presentation of a patient with advanced prostate cancer, massive ascites and peritoneal metastasis: Case report and literature review. AB - We describe the case of a patient with prostate cancer, ascites, omental and bone metastases, an extremely rare clinical variant that warrants further investigation, and review the relevant literature. PMID- 26257951 TI - Development of a low grade lymphoma in the mastoid bone in a patient with atypical Cogan's syndrome: A case report. AB - Cogan's syndrome is a rare disorder characterized by ocular and audiovestibular manifestations in its typical form and caries a wide variety of atypical manifestations. It is considered as an autoimmune disease. We present the first case in the literature of a 67 year old woman with the development of low grade non-Hodgkin lymphoma (NHL) in the mastoid bone in a pre-existing history of atypical Cogan's syndrome. The anatomical development of NHL was to a "target" organ of Cogan's syndrome, which is the inner ear. PMID- 26257952 TI - Mid-infrared laser-spectroscopic sensing of chemical species. AB - This letter reports on mid-infrared laser-based detection and analysis of chemical species. Emphasis is put on broadly tunable laser sources and sensitive detection schemes. Selected examples from our lab illustrate the performance and potential of such systems in various areas including environmental and medical sensing. PMID- 26257953 TI - Ramsey CB, Dee MW, Rowland JM, Higham TFG, Harris SA, Brock F, et al. Radiocarbon based chronology for dynastic Egypt. Science 2010;328:1554. PMID- 26257954 TI - Combination Antiretroviral Therapy for HIV in Rwandan Adults: Clinical Outcomes and Impact on Reproductive Health up to 24 Months. AB - Adult women (n = 113) and men (n = 100) initiating combination antiretroviral therapy (cART) and women not yet eligible for cART (n = 199) in Kigali, Rwanda, were followed for 6-24 months between 2007 and 2010. In the cART groups, 21% of patients required a drug change due to side effects and 11% of patients had virological failure (defined as >1,000 HIV RNA copies/mL) after 12 months of cART. About a third of the pregnancies since HIV diagnosis were unintended. The proportion of women in the pre-cART group using modern contraception other than condoms (50%) was similar to women in the general population, but this proportion was only 25% in women initiating cART. Of the women who carried at least one pregnancy to term since having been diagnosed HIV-positive, a third reported to have participated in a prevention-of-mother-to-child-transmission (PMTCT, option A) intervention. Many patients were coinfected with herpes simplex virus type 2 (79-92%), human papillomavirus (38-53%), and bacterial sexually transmitted infections (STIs) with no differences between groups. We applaud the Rwandan government for having strengthened family planning and PMTCT services and for having introduced HPV vaccination in recent years, but additional work is needed to strengthen STI and HPV-related cancer screening and management in the HIV positive population. PMID- 26257955 TI - Intravenous Iron Therapy in Patients with Iron Deficiency Anemia: Dosing Considerations. AB - Objective. To provide clinicians with evidence-based guidance for iron therapy dosing in patients with iron deficiency anemia (IDA), we conducted a study examining the benefits of a higher cumulative dose of intravenous (IV) iron than what is typically administered. Methods. We first individually analyzed 5 clinical studies, averaging the total iron deficit across all patients utilizing a modified Ganzoni formula; we then similarly analyzed 2 larger clinical studies. For the second of the larger studies (Study 7), we also compared the efficacy and retreatment requirements of a cumulative dose of 1500 mg ferric carboxymaltose (FCM) to 1000 mg iron sucrose (IS). Results. The average iron deficit was calculated to be 1531 mg for patients in Studies 1-5 and 1392 mg for patients in Studies 6-7. The percentage of patients who were retreated with IV iron between Days 56 and 90 was significantly (p < 0.001) lower (5.6%) in the 1500 mg group, compared to the 1000 mg group (11.1%). Conclusions. Our data suggests that a total cumulative dose of 1000 mg of IV iron may be insufficient for iron repletion in a majority of patients with IDA and a dose of 1500 mg is closer to the actual iron deficit in these patients. PMID- 26257956 TI - Semantic Processing Impairment in Patients with Temporal Lobe Epilepsy. AB - The impairment in episodic memory system is the best-known cognitive deficit in patients with temporal lobe epilepsy (TLE). Recent studies have shown evidence of semantic disorders, but they have been less studied than episodic memory. The semantic dysfunction in TLE has various cognitive manifestations, such as the presence of language disorders characterized by defects in naming, verbal fluency, or remote semantic information retrieval, which affects the ability of patients to interact with their surroundings. This paper is a review of recent research about the consequences of TLE on semantic processing, considering neuropsychological, electrophysiological, and neuroimaging findings, as well as the functional role of the hippocampus in semantic processing. The evidence from these studies shows disturbance of semantic memory in patients with TLE and supports the theory of declarative memory of the hippocampus. Functional neuroimaging studies show an inefficient compensatory functional reorganization of semantic networks and electrophysiological studies show a lack of N400 effect that could indicate that the deficit in semantic processing in patients with TLE could be due to a failure in the mechanisms of automatic access to lexicon. PMID- 26257957 TI - Evaluation of Anthropometric and Metabolic Parameters in Obstructive Sleep Apnea. AB - AIMS: Sleep disorders have recently become a significant public health problem worldwide and have deleterious health consequences. Obstructive sleep apnea (OSA) is the most common type of sleep-related breathing disorders. We aimed to evaluate anthropometric measurements, glucose metabolism, and cortisol levels in patients with obstructive sleep apnea (OSA). MATERIALS AND METHODS: A total of 50 patients with a body mass index >=30 and major OSA symptoms were included in this study. Anthropometric measurements of the patients were recorded and blood samples were drawn for laboratory analysis. A 24-hour urine sample was also collected from each subject for measurement of 24-hour cortisol excretion. Patients were divided equally into 2 groups according to polysomnography results: control group with an apnea-hypopnea index (AHI) <5 (n = 25) and OSA group with an AHI >=5 (n = 25). RESULTS: Neck and waist circumference, fasting plasma glucose, HbA1c, late-night serum cortisol, morning serum cortisol after 1 mg dexamethasone suppression test, and 24-hour urinary cortisol levels were significantly higher in OSA patients compared to control subjects. Newly diagnosed DM was more frequent in patients with OSA than control subjects (32% versus 8%, p = 0.034). There was a significant positive correlation between AHI and neck circumference, glucose, and late-night serum cortisol. CONCLUSIONS: Our study indicates that increased waist and neck circumferences constitute a risk for OSA regardless of obesity status. In addition, OSA has adverse effects on endocrine function and glucose metabolism. PMID- 26257958 TI - Effects of Myeloperoxidase-Induced Oxidation on Antiatherogenic Functions of High Density Lipoprotein. AB - High-density lipoprotein (HDL) has protective effects against the development of atherosclerosis; these effects include reverse cholesterol transport, antioxidant ability, and anti-inflammation. Myeloperoxidase (MPO) secreted by macrophages in atherosclerotic lesions generates tyrosyl radicals in apolipoprotein A-I (apoA-I) molecules, inducing the formation of apoA-I/apoA-II heterodimers through the tyrosine-tyrosine bond in HDL. Functional characterization of HDL oxidized by MPO could provide useful information about the significance of apoA-I/apoA-II heterodimers measurement. We investigated the effects of MPO-induced oxidation on the antiatherogenic functions of HDL as described above. The antioxidant ability of HDL, estimated as the effect on LDL oxidation induced by copper sulfate, was not significantly affected after MPO oxidation. HDL reduced THP-1 monocyte migration by suppressing the stimulation of human umbilical vein endothelial cells induced by lipopolysaccharide (LPS). MPO-oxidized HDL also showed inhibition of THP-1 chemotaxis, but the extent of inhibition was significantly attenuated compared to intact HDL. MPO treatment did not affect the cholesterol efflux capacity of HDL from [(3)H]-cholesterol-laden macrophages derived from THP 1 cells. The principal effect of MPO oxidation on the antiatherogenic potential of HDL would be the reduction of anti-inflammatory ability, suggesting that measurement of apoA-I/apoA-II heterodimers might be useful to estimate anti inflammatory ability of HDL. PMID- 26257959 TI - Effect of Simvastatin on Arterial Stiffness in Patients with Statin Myalgia. AB - Statins reduce arterial stiffness but are also associated with mild muscle complaints. It is unclear whether individuals with muscle symptoms experience the same vascular benefit or whether statins affect striated and smooth muscle cells differently. We examined the effect of simvastatin treatment on arterial stiffness in patients who did versus those who did not exhibit muscle symptoms. Patients with a history of statin-related muscle complaints (n = 115) completed an 8 wk randomized, double-blind, cross-over trial of daily simvastatin 20 mg and placebo. Serum lipids and pulse wave velocity (PWV) were assessed before and after each treatment. Muscle symptoms with daily simvastatin treatment were reported by 38 patients (33%). Compared to baseline, central PWV decreased (P = 0.01) following simvastatin treatment but not placebo (drug * time interaction: P = 0.047). Changes in central PWV with simvastatin treatment were not influenced by myalgia status or time on simvastatin (P >= 0.15). Change in central PWV after simvastatin treatment was inversely correlated with age (r = -0.207, P = 0.030), suggesting that advancing age is associated with enhanced statin-mediated arterial destiffening. In patients with a history of statin-related muscle complaints, the development of myalgia with short-term simvastatin treatment did not attenuate the improvement in arterial stiffness. PMID- 26257960 TI - Neural Stem Cell Transplant-Induced Effect on Neurogenesis and Cognition in Alzheimer Tg2576 Mice Is Inhibited by Concomitant Treatment with Amyloid-Lowering or Cholinergic alpha7 Nicotinic Receptor Drugs. AB - Stimulating regeneration in the brain has the potential to rescue neuronal networks and counteract progressive pathological changes in Alzheimer's disease (AD). This study investigated whether drugs with different mechanisms of action could enhance neurogenesis and improve cognition in mice receiving human neural stem cell (hNSC) transplants. Six- to nine-month-old AD Tg2576 mice were treated for five weeks with the amyloid-modulatory and neurotrophic drug (+)-phenserine or with the partial alpha7 nicotinic receptor (nAChR) agonist JN403, combined with bilateral intrahippocampal hNSC transplantation. We observed improved spatial memory in hNSC-transplanted non-drug-treated Tg2576 mice but not in those receiving drugs, and this was accompanied by an increased number of Doublecortin- (DCX-) positive cells in the dentate gyrus, a surrogate marker for newly generated neurons. Treatment with (+)-phenserine did however improve graft survival in the hippocampus. An accumulation of alpha7 nAChR-expressing astrocytes was observed around the injection site, suggesting their involvement in repair and scarring processes. Interestingly, JN403 treatment decreased the number of alpha7 nAChR-expressing astrocytes, correlating with a reduction in the number of DCX-positive cells in the dentate gyrus. We conclude that transplanting hNSCs enhances endogenous neurogenesis and prevents further cognitive deterioration in Tg2576 mice, while simultaneous treatments with (+)-phenserine or JN403 result in countertherapeutic effects. PMID- 26257962 TI - Neural Rhythms of Change: Long-Term Improvement after Successful Treatment in Children with Disruptive Behavior Problems. AB - Neural changes were investigated for children with disruptive behavior problems one year after a treatment program ended. Thirty-nine children and their parents visited the research lab before, after, and a year after treatment ended. During those lab visits, electroencephalography (EEG) was recorded during a challenging Go/No-go task. Treatment consisted of intensive 14-week combined cognitive behavioral therapy and parent management training sessions. For the analysis, participants were divided into long-term improvers (IMPs) and long-term nonimprovers (NIMPs) based on changes in their externalizing problem scores. The results showed early no-go theta power (4-8 Hz, 100-250 ms) decreased for long term IMPs compared to NIMPs. When participants were divided based on changes in their comorbid internalizing symptoms, effects were stronger and reductions in theta power were found for early as well as later phases (250-650 ms). We provided preliminary evidence that theta power is a useful neural measure to trace behavioral change linked to improved self-regulation even up to a year after treatment ended. Results may have implications for the characterization of children with disruptive behavior problems and may lead to the development of novel markers of treatment success. PMID- 26257961 TI - Decoding the Formation of New Semantics: MVPA Investigation of Rapid Neocortical Plasticity during Associative Encoding through Fast Mapping. AB - Neocortical structures typically only support slow acquisition of declarative memory; however, learning through fast mapping may facilitate rapid learning induced cortical plasticity and hippocampal-independent integration of novel associations into existing semantic networks. During fast mapping the meaning of new words and concepts is inferred, and durable novel associations are incidentally formed, a process thought to support early childhood's exuberant learning. The anterior temporal lobe, a cortical semantic memory hub, may critically support such learning. We investigated encoding of semantic associations through fast mapping using fMRI and multivoxel pattern analysis. Subsequent memory performance following fast mapping was more efficiently predicted using anterior temporal lobe than hippocampal voxels, while standard explicit encoding was best predicted by hippocampal activity. Searchlight algorithms revealed additional activity patterns that predicted successful fast mapping semantic learning located in lateral occipitotemporal and parietotemporal neocortex and ventrolateral prefrontal cortex. By contrast, successful explicit encoding could be classified by activity in medial and dorsolateral prefrontal and parahippocampal cortices. We propose that fast mapping promotes incidental rapid integration of new associations into existing neocortical semantic networks by activating related, nonoverlapping conceptual knowledge. In healthy adults, this is better captured by unique anterior and lateral temporal lobe activity patterns, while hippocampal involvement is less predictive of this kind of learning. PMID- 26257963 TI - Giant Cell Myocarditis: Not Always a Presentation of Cardiogenic Shock. AB - Giant cell myocarditis is a rare and often fatal disease. The most obvious presentation often described in the literature is one of rapid hemodynamic deterioration due to cardiogenic shock necessitating urgent consideration of mechanical circulatory support and heart transplantation. We present the case of a 60-year-old man whose initial presentation was consistent with myopericarditis but who went on to develop a rapid decline in left ventricular systolic function without overt hemodynamic compromise or dramatic symptomatology. Giant cell myocarditis was confirmed via endomyocardial biopsy. Combined immunosuppression with corticosteroids and calcineurin inhibitor resulted in resolution of symptoms and sustained recovery of left ventricular function one year later. Our case highlights that giant cell myocarditis does not always present with cardiogenic shock and should be considered in the evaluation of new onset cardiomyopathy of uncertain etiology as a timely diagnosis has distinct clinical implications on management and prognosis. PMID- 26257964 TI - Malignant Course of Anomalous Left Coronary Artery Causing Sudden Cardiac Arrest: A Case Report and Review of the Literature. AB - Sudden cardiac arrest has been reported to occur in patients with congenital anomalous coronary artery disease. About 80% of the anomalies are benign and incidental findings at the time of catheterization. We present a case of sudden cardiac arrest caused by anomalous left anterior descending artery. 61-year-old African American female was brought to the emergency department after sudden cardiac arrest. Initial EKG showed sinus rhythm with RBBB and LAFB with nonspecific ST-T wave changes. Coronary angiogram revealed no atherosclerotic disease. The left coronary artery was found to originate from the right coronary cusp. Cardiac CAT scan revealed similar findings with interarterial and intramural course. Patient received one-vessel arterial bypass graft to her anomalous coronary vessel along with a defibrillator for secondary prevention. Sudden cardiac arrest secondary to congenital anomalous coronary artery disease is characterized by insufficient coronary flow by the anomalous left coronary artery to meet elevated left ventricular (LV) myocardial demand. High risk defects include those involved with the proximal coronary artery or coursing of the anomalous artery between the aorta and pulmonary trunk. Per guidelines, our patient received one vessel bypass graft to her anomalous vessel. It is important for clinicians to recognize such presentations of anomalous coronary artery. PMID- 26257965 TI - Severe Hyperthyroidism Presenting with Acute ST Segment Elevation Myocardial Infarction. AB - Introduction. Acute myocardial infarction is life-threatening. A cardiac troponin rise accompanied by typical symptoms, ST elevation or depression is diagnostic of acute myocardial infarction. Here, we report an unusual case of a female who was admitted with chest pain. However, she did not present with a typical profile of an acute myocardial infarction patient. Case Presentation. A 66-year-old Han nationality female presented with chest pain. The electrocardiogram (ECG) revealed arched ST segment elevations and troponin was elevated. However, the coronary angiography showed a normal coronary arterial system. Thyroid function tests showed that this patient had severe hyperthyroidism. Conclusion. Our case highlights the possibility that hyperthyroidism may cause a large area of myocardium injury and ECG ST segment elevation. We suggest routine thyroid function testing in patients with chest pain. PMID- 26257966 TI - Traumatic Cervical Spondyloptosis in a Neurologically Stable Patient: A Therapeutic Challenge. AB - This is a case report of a neurologically intact patient following posttraumatic cervical spondyloptosis. We discuss the disease, management protocol and some surgical nuances to prevent any damage to the cord during different stages of its treatment. PMID- 26257967 TI - Rare Strain of Vibrio cholerae Septicemia in a Patient with Multiple Myeloma. AB - Introduction. Non-O1/non-O139 is a rare strain of Vibrio cholera that has been documented to cause significant morbidity and mortality in the immunosuppressed population. Case Presentation. A patient with multiple myeloma develops non O1/non-O139 Vibrio cholera septicemia, leading to multiorgan failure and ultimately death. Discussion. An exceedingly rare strain of Vibrio cholera, non O1/non-O139, may be an important factor of morbidity and mortality in certain immunosuppressed populations, such as patients with multiple myeloma and malignancies. Conclusion. Bacteremia involving generally noninvasive microbes, such as non-O1/non-O139 Vibrio cholerae, can have significant deleterious effects in the immunosuppressed patients as shown by this case report. Physicians need to be more diligent when treating these patients. PMID- 26257968 TI - Early Onset Primary Hyperparathyroidism Associated with a Novel Germline Mutation in CDKN1B. AB - Individuals presenting with primary hyperparathyroidism (PHPT) at a young age commonly have an underlying germline gene mutation in one of the following genes: MEN1, CASR, or CDC73. A small number of families with primary hyperparathyroidism have been identified with germline mutations in CDKN1B and those patients with primary hyperparathyroidism have almost exclusively been women who present in middle age suggesting that the age of onset of PHPT in MEN4 may be later than that of MEN1. We present a case of apparently sporadic PHPT presenting in adolescence with single gland disease associated with a novel CDKN1B germline mutation (heterozygote for a missense mutation in exon 1 of the CDKN1B gene (c.378G>C) (p.E126D)). The implication from this case is that CDKN1B germline mutations may be associated with PHPT at an earlier age than previously thought. PMID- 26257969 TI - Life Threatening Idiopathic Recurrent Angioedema Responding to Cannabis. AB - We present a case of a 27-year-old man with recurrent episodes of angioedema since he was 19, who responded well to treatment with medical grade cannabis. Initially, he responded to steroids and antihistamines, but several attempts to withdraw treatment resulted in recurrence. In the last few months before prescribing cannabis, the frequency and severity of the attacks worsened and included several presyncope events, associated with scrotal and neck swelling. No predisposing factors were identified, and extensive workup was negative. The patient reported that he was periodically using cannabis socially and that during these periods he was free of attacks. Recent data suggest that cannabis derivatives are involved in the control of mast cell activation. Consequently, we decided to try a course of inhaled cannabis as modulators of immune cell functions. The use of inhaled cannabis resulted in a complete response, and he has been free of symptoms for 2 years. An attempt to withhold the inhaled cannabis led to a recurrent attack within a week, and resuming cannabis maintained the remission, suggesting a cause and effect relationship. PMID- 26257970 TI - Professional Acquisition of M. bovis in Calabria Region (Southern Italy): A Challenging Case of Osteomyelitis in a Migrant Patient from Bulgaria. AB - We report herein the first case of a coinfection with Brucella spp., M. bovis, and Enterobacter cloacae in a butcher who moved from Bulgaria to Italy. Molecular typing suggested professional acquisition of M. bovis in Italy. So, surveillance and preventive measures need to be implemented. PMID- 26257971 TI - Balloon Cell Urethral Melanoma: Differential Diagnosis and Management. AB - Introduction. Primary malignant melanoma of the urethra is a rare tumour (0.2% of all melanomas) that most commonly affects the meatus and distal urethra and is three times more common in women than men. Case. A 76-year-old lady presented with vaginal pain and discharge. On examination, a 4 cm mass was noted in the vagina and biopsy confirmed melanoma of a balloon type. Preoperative CT showed no distant metastases and an MRI scan of the pelvis demonstrated no associated lymphadenopathy. She underwent anterior exenterative surgery and vaginectomy also. Histology confirmed a urethral nodular malignant melanoma. Discussion. First-line treatment of melanoma is often surgical. Adjuvant treatment including chemotherapy, radiotherapy, or immunotherapy has also been reported. Even with aggressive management, malignant melanoma of the urogenital tract generally has a poor prognosis. Recurrence rates are high and the mean period between diagnosis and recurrence is 12.5 months. A 5-year survival rate of less than 20% has been reported in balloon cell melanomas along with nearly 20% developing local recurrence. Conclusion. To the best of our knowledge, this case is the first report of balloon cell melanoma arising in the urethra. The presentation and surgical management has been described and a literature review provided. PMID- 26257972 TI - Benign Recurrent Sixth (Abducens) Nerve Palsy following Measles-Mumps-Rubella Vaccination. AB - Benign, isolated, recurrent sixth nerve palsy is rare in children. It may be associated with febrile viral illness and vaccination in exceptional circumstances although this is a diagnosis of exclusion. Here, we present the case of a 2-year-old Caucasian girl who developed recurrent 6th nerve palsy following vaccination with the measles-mumps-rubella (MMR) vaccine. No underlying pathology was identified following extensive investigations and followup. There is limited data available on the pathophysiology of vaccination-related nerve palsies. As with all previous reports of cranial nerve palsies following vaccination, there was complete resolution in this case. Long term followup with repeated physical examination and investigations is warranted to avoid missing severe pathology and operating unnecessarily. PMID- 26257973 TI - A Case of Docetaxel Induced Myositis and Review of the Literature. AB - In phase I and II trials taxane chemotherapeutic agents reported side effects, including myelosuppression, peripheral edema, and fluid retention. With further use of these agents, studies in the late 1980s and early 1990s began to report peripheral neuropathy and proximal muscle weakness as common complaints, the later with unexplained pathophysiology. We report a 65-year-old Hispanic woman with estrogen receptor (ER) and progesterone receptor (PR) positive invasive ductal breast carcinoma who presented with right thigh pain and swelling eight days after her third infusion of docetaxel (a taxane chemotherapeutic) and cyclophosphamide. Laboratory findings were notable for elevation in creatine phosphokinase (CPK), aldolase, and erythrocyte sedimentation rate (ESR); a magnetic resonance imaging (MRI) of her lower extremities showed evidence of bilateral muscle edema involving the anterior compartment muscles of the thighs. A workup to rule out other causes of myositis was negative. Docetaxel was not reintroduced and the patient improved with corticosteroids. Since 2005 this is, to our knowledge, the fifth reported case of docetaxel related inflammatory myositis. Taxanes have been noted to cause disabling but transient arthralgias and myalgias; it is important to consider the possibility of inflammatory myopathy as a possible complication in patients undergoing treatment with these agents. PMID- 26257974 TI - Conservative Management of an Iatrogenic Esophageal Tear in Kenya. AB - Since its description over 250 years ago, diagnosis of esophageal perforation remains challenging, its management controversial, and its mortality high. This rare, devastating, mostly iatrogenic, condition can quickly lead to severe complications and death due to an overwhelming inflammatory response to gastric contents in the mediastinum. Diagnosis is made with the help of esophagograms and although such tears have traditionally been managed via aggressive surgical approach, recent reports emphasize a shift in favor of nonoperative care which unfortunately remains controversial. We here present a case of an iatrogenic esophageal tear resulting from a routine esophagoscopy in a 50-year-old lady presenting with dysphagia. The esophageal tear, almost missed, was eventually successfully managed conservatively, thanks to a relatively early diagnosis. PMID- 26257975 TI - Sarcomatoid Renal Cell Carcinoma Metastasis to the Penis. AB - Secondary cancers of the penis are extremely uncommon with less than 300 cases reported in the past 100 years. These cancers are most frequently a result of an aggressive or poorly managed primary prostate or bladder cancer and rarely a metastasis from a primary kidney tumor. Currently, there is no published literature which describes the spread of sarcomatoid renal cell carcinoma (SRCC) to the penis. In this report, we present a 55-year-old-man who presented with a large right-sided SRCC which metastasized to the base of his penis within 1 month of symptom onset. We also discuss the possible route of metastasis based on primary tumor size and location within the retroperitoneum. PMID- 26257976 TI - Prelaminated Gracilis Flap with Buccal Mucosal Graft for Salvage of Devastated Urethra. AB - In patients with devastated bulbous urethra, that is, bulbar necrosis, failed fasciocutaneous repairs and "watering can perineum" repair options are limited by paucity of reliable local tissue suitable for reconstruction. In this case report we demonstrate a novel variation of a two-stage technique for reconstruction of a devastated bulbous urethra in a 57-year-old male who suffered penetrating trauma to his previously reconstructed urethra. Because of extensive loss of local tissue from the prior reconstruction and subsequent trauma and infection a 2 stage technique with use of gracilis was employed. This technique involved creation of two independently vascularized urethral hemi-plates prelaminated with buccal mucosa graft (BMG). In the first stage the dorsal plate was created by quilting buccal graft onto corpora cavernosa to create a temporary augmented perineal urethrostomy. In the same stage the future ventral neourethral plate was created by grafting another BMG onto the exposed distal gracilis muscle. Eight weeks later the two prelaminated plates were anastomosed by tunneling the gracilis-BMG composite into the perineum. At 8-month follow-up patient has normal voiding and continence. To our knowledge this is the first report of reconstructing an entire segment of devastated urethra in such a manner. PMID- 26257977 TI - A Major Complication in Micropercutaneous Nephrolithotomy: Upper Calyceal Perforation with Extrarenal Migration of Stone Fragments due to Increased Intrarenal Pelvic Pressure. AB - Micropercutaneous nephrolithotomy is a safe and efficient technique for appropriate sized stones. It is performed through a 4.85 Fr all-seeing needle and stones are fragmented into dust, without the need for tract dilatation, unlike other percutaneous nephrolithotomy types. Even though micropercutaneous nephrolithotomy has many advantages, increase in intrapelvic pressure during surgery may cause rare but serious complications. Herein we report a case of micropercutaneous nephrolithotomy in a 20-year-old woman with a 20 mm right renal pelvis stone and present an undesired outcome of this complication, upper calyceal perforation. Right lower calyceal access was performed with 4.85 Fr all seeing needle and 2 cm renal pelvis stone was fragmented by 272 MUm Holmium-Yag laser system. Upper calyceal perforation and infrahepatic accumulation of stone fragments were detected by fluoroscopy during the surgery. Postoperative imagings revealed perirenal urinoma, perirenal and infrahepatic stone fragments, and lower calyceal stone fragments inside the system. On second postoperative day, minipercutaneous nephrolithotomy and double J catheter insertion procedures were applied for effective drainage and stone clearance. Risk of calyceal perforation and urinoma formation, due to increased intrapelvic pressure during micropercutaneous nephrolithotomy, should be kept in mind. PMID- 26257978 TI - Evaluating Adult's Competency: Application of the Competency Assessment Process. AB - Competency assessment of adults with cognitive impairment or mental illness is a complex process that can have significant consequences for their rights. Some models put forth in the scientific literature have been proposed to guide health and social service professionals with this assessment process, but none of these appear to be complete. A new model, the Competency Assessment Process (CAP), was presented and validated in other studies. This paper adds to this corpus by presenting both the CAP model and the results of a survey given to health and social service professionals on its practical application in their clinical practice. The survey was administered to 35 participants trained in assessing competency following the CAP model. The results show that 40% of participants use the CAP to guide their assessment and the majority of those who do not yet use it plan to do so in the future. A large majority of participants consider this to be a relevant model and believe that all interdisciplinary teams should use it. These results support the relevance of the CAP model. Further research is planned to continue the study of the application of CAP in healthcare facilities. PMID- 26257979 TI - Utility of Shear Wave Elastography for Diagnosing Chronic Autoimmune Thyroiditis. AB - The aims of this study were to evaluate the utility of shear wave elastography (SWE) using acoustic radiation force impulse (ARFI) for diagnosing chronic autoimmune thyroiditis (CAT) and to verify the effect of fibrotic thyroid tissue on shear wave velocity (SWV). The subjects were 229 patients with 253 normal thyroid lobes (controls) and 150 CAT lobes. The SWV for CAT (2.47 +/- 0.57 m/s) was significantly higher than that for controls (1.59 +/- 0.41 m/s) (P < 0.001). The area under the receiver operating characteristics (ROC) curve for CAT was 0.899, and the SWV cut-off value was 1.96 m/s. The sensitivity, specificity, and diagnostic accuracy were 87.4%, 78.7%, and 85.1%, respectively. Levels of anti thyroperoxidase antibodies and thyroid isthmus thickness were correlated with tissue stiffness in CAT. However, there was no correlation between levels of anti thyroglobulin antibodies and tissue stiffness. Quantitative SWE is useful for diagnosing CAT, and it is possible that SWE can be used to evaluate the degree of fibrosis in patients with CAT. PMID- 26257980 TI - Effects of Oxygen Element and Oxygen-Containing Functional Groups on Surface Wettability of Coal Dust with Various Metamorphic Degrees Based on XPS Experiment. AB - To investigate the difference of surface oxygen element and oxygen-containing functional groups among coal dusts with different metamorphic degrees and their influence on surface wettability, a series of X-ray photoelectron spectroscopy experiments on 6 coal samples are carried out. The result demonstrates that the O/C ratio of coal surface shows an overall increasing trend compared with the result of its elements analysis. As the metamorphic degree increases, the O/C ratio on the surface gradually declines and the hydrophilic groups tend to fall off from coal surface. It could be found that different coals show different surface distributions of carboxyl and hydroxyl which are considered as the greatest promoter to the wettability of coal surface. With the change of metamorphic degree, the distribution of ether group is irregular while the carbonyl distribution keeps stable. In general, as the metamorphic degree goes higher, the content of oxygen-containing polar group tends to reduce. According to the measurement results, the contact angle is negatively related to the content of oxygen element, surface oxygen, and polar groups. In addition, compared with surface oxygen content, the content of oxygen-containing polar group serves as a more reasonable indicator of coal dust wettability. PMID- 26257981 TI - Neuroendoscopic treatment of symptomatic giant Virchow-Robin spaces. AB - BACKGROUND: Virchow-Robin spaces (VRS) or perivascular spaces are interstitial cystic spaces surrounding the vasculature of brain parenchyma and course from the subarachnoid space. Small VRS (<2 mm) appear in all age groups, but can enlarge and be confused with other lesions like cystic neoplasms. These enlarged VRS are termed giant tumefactive perivascular spaces (GRPVS). CASE DESCRIPTION: We present the case of a 50-year-old male who presents with right eye pain, blurred vision, headache, and gait imbalance. He was diagnosed with GRPVS and underwent an endoscopic third ventriculostomy and cyst fenestration. Postoperative imaging showed a decrease in size of the ventricular system with evidence of flow through the aqueduct and ventriculostomy. Brainstem VRS cysts decreased in size. CONCLUSION: Unlike the other small number of case reports, this patient is unique in his age of presentation and successful endoscopic method of treatment. The endoscopic approach provided great exposure and adequate access to the lesions. Clinically, symptoms improved, cyst size decreased, and need for permanent shunt placement was averted. PMID- 26257982 TI - Erratum: Pedunculated intraventricular subependymoma: Review of the literature and illustration of classical presentation through a clinical case: Erratum. AB - [This corrects the article on p. 117 in vol. 5, PMID: 25101212.]. PMID- 26257983 TI - Multiple cerebral hydatid cysts in 8-year-old boy: A case report and literature review of a rare presentation. AB - BACKGROUND: Multiple cerebral hydatid cysts are very rare with only a few reports in the literature detailing diagnostic workup, medical management, surgical techniques, possible complications, and outcomes. CASE DESCRIPTION: We present the case of an 8-year-old boy who presented with progressively worsening headaches, vomiting, and intermittent fever since 20 days. Diagnostic workup was performed, and magnetic resonance imaging revealed multiple intracranial cysts predominantly in the right frontal region with significant mass effect. A total of 19 intracranial cysts were removed surgically, and the child recovered uneventfully. CONCLUSIONS: Neurosurgeons should keep hydatidosis in the list of differentials when evaluating patients with cystic diseases of the brain. Although the removal of such cysts is challenging, outcomes are excellent when cysts are evacuated without rupture and patients show complete resolution of symptoms. PMID- 26257984 TI - C1-C2 cryptic cerebrospinal fluid leak directly identified by pressurized radionuclide cisternography: Case report and review of the literature. AB - BACKGROUND: Patients with chronic postural headaches may suffer from spontaneous intracranial hypotension (SIH). Trauma, degenerative disc spurring and connective tissue disorders are documented risk factors; in most cases there is no inciting event. Despite sophisticated means of evaluating the neuraxis, many cerebrospinal fluid (CSF) leaks are radiographically occult and treatment is focused on thoracic and cervical-thoracic regions. Although lumbar epidural blood patch (EBP) is the initial treatment of choice after failed conservative management, several studies document the need for treatment aimed at the specific leak area. CASE DESCRIPTION: This report describes the case of a 42-year-old female with scleroderma and sudden onset postural headaches. Magnetic resonance imaging revealed diffuse pachymeningeal enhancement suggestive of intracranial hypotension. Computed tomographic myelography demonstrated a collection of fluid ventral to the cervical thecal sac; an exact location for CSF egress was not identified. Conservative measures followed by lumbar EBP failed to alleviate her symptoms. The patient underwent placement of a lumbar drain and dynamic radionuclide cisternography (RIC). Panoramic images of the spine were taken at the time of the pressurized saline injection. The CSF leak was clearly visualized at C1-2. Treatment was focused at this region using percutaneous injection of autologous blood and fibrin glue. CONCLUSION: SIH is disabling if left untreated. Spinal CSF leaks are often discrete and difficult to identify using static imaging. The use of pressurized, RIC by lumbar drain injection allows for the real-time evaluation of CSF dynamics and can more precisely identify slow flow leaks often missed with static imaging. PMID- 26257986 TI - The death of Stalin - was it a natural death or poisoning? PMID- 26257985 TI - Chronic subdural hematoma: Surgical management and outcome in 986 cases: A classification and regression tree approach. AB - BACKGROUND: Chronic subdural hematoma (CSDH) is one of the most common clinical entities in daily neurosurgical practice which carries a most favorable prognosis. However, because of the advanced age and medical problems of patients, surgical therapy is frequently associated with various complications. This study evaluated the clinical features, radiological findings, and neurological outcome in a large series of patients with CSDH. METHODS: A classification and regression tree (CART) technique was employed in the analysis of data from 986 patients who were operated at Asclepeion General Hospital of Athens from January 1986 to December 2011. Burr holes evacuation with closed system drainage has been the operative technique of first choice at our institution for 29 consecutive years. A total of 27 prognostic factors were examined to predict the outcome at 3-month postoperatively. RESULTS: Our results indicated that neurological status on admission was the best predictor of outcome. With regard to the other data, age, brain atrophy, thickness and density of hematoma, subdural accumulation of air, and antiplatelet and anticoagulant therapy were found to correlate significantly with prognosis. The overall cross-validated predictive accuracy of CART model was 85.34%, with a cross-validated relative error of 0.326. CONCLUSIONS: Methodologically, CART technique is quite different from the more commonly used methods, with the primary benefit of illustrating the important prognostic variables as related to outcome. Since, the ideal therapy for the treatment of CSDH is still under debate, this technique may prove useful in developing new therapeutic strategies and approaches for patients with CSDH. PMID- 26257988 TI - CTREC: C-arm Tracking and Reconstruction using Elliptic Curves. AB - C-arm fluoroscopy is ubiquitous in contemporary surgery, but it lacks the ability to accurately reconstruct three-dimensional information, attributable to the difficulty in obtaining the pose of X-ray images in 3D space. We propose a unified mathematical framework to address the issues of intra-operative pose estimation, correspondence and reconstruction, using simple elliptic curves. In contrast to other fiducial-based tracking methods, our method uses a single ellipse to constrain 5 out of 6 degrees of freedom of C-arm pose, along with randomly distributed unknown points in the imaging volume (either naturally present or induced by randomly placed beads or other markers in the image space) from two images/views to completely recover the C-arm pose. Preliminary phantom experiments indicate an average C-arm tracking accuracy of 0.51 degrees and 0.12 degrees STD. The method appears to be sufficiently accurate and appealing for many clinical applications, since it uses a simple elliptic fiducial coupled with patient information and has very minimal interference with the workspace. PMID- 26257987 TI - Atypical pleomorphic neoplasms of the pineal gland: Case report and review of the literature. AB - BACKGROUND: Pineal region tumors are rare and diverse. Among them exist reports of pleomorphic xanthroastrocytoma (PXA) and pleomorphic granular cell astrocytoma (PGCA) of the pineal gland. These related tumors are remarkably similar sharing pleomorphic histologic features with only minor immunohistochemical and ultrastructural differences. CASE DESCRIPTION: We present a case of a 42-year old right-handed woman presented with a longstanding history of migraine headaches which had worsened over the two months leading up to her hospitalization. MRI revealed a 1.7 * 1.3 * 1.6 cm intensely enhancing lesion originating in the pineal gland. The tumor closely resembled PGCA but did not strictly fit the diagnostic requirements of either PGCA or PXA. CONCLUSION: The present case highlights the exotic nature of pineal region tumors with pleomorphic cell histology. Given the diverse range of tumors encountered in the pineal region, pathological confirmation is mandatory. Favorable clinical outcomes demonstrate that surgical resection alone can yield excellent long-term results for tumors falling within the spectrum of pleomorphic lesions of the pineal gland. PMID- 26257989 TI - Role of amyloid beta in the induction of lipolysis and secretion of adipokines from human adipose tissue. AB - Amyloid-beta (Abeta) peptide, which is generated from proteolytic cleavage of amyloid precursor protein (APP), is a key molecule involved in the pathology of Alzheimer disease. Both APP and Abeta peptides are expressed in adipose tissue, however it is currently unclear whether Abeta can affect the key functions of adipose tissue. We aimed to explore whether Abeta affected lipolysis and adipokine secretion in cultured human adipose tissue. We found that Abeta25-35, which contains the main functional domain of the Abeta, stimulated lipolysis via PKA and ERK1/2-dependent pathways and that Abeta25-35 induced leptin and IL-6 secretion. It is concluded that Abeta peptide exerts functional effects on adipose tissue that may lead to increased release of free fatty acids and pro inflammatory adipokines. PMID- 26257990 TI - Pathways commonly dysregulated in mouse and human obese adipose tissue: FAT/CD36 modulates differentiation and lipogenesis. AB - Obesity is linked to adipose tissue hypertrophy (increased adipocyte cell size) and hyperplasia (increased cell number). Comparative analyses of gene datasets allowed us to identify 1426 genes which may represent common adipose phenotype in humans and mice. Among them we identified several adipocyte-specific genes dysregulated in obese adipose tissue, involved in either fatty acid storage (acyl CoA synthase ACSL1, hormone-sensitive lipase LIPE, aquaporin 7 AQP7, perilipin PLIN) or cell adhesion (fibronectin FN1, collagens COL1A1, COL1A3, metalloprotein MMP9, or both (scavenger receptor FAT/CD36). Using real-time analysis of cell surface occupancy on xCELLigence system we developed a new method to study lipid uptake and differentiation of mouse 3T3L1 fibroblasts and human adipose stem cells. Both processes are regulated by insulin and fatty acids such as oleic acid. We showed that fatty acid addition to culture media increased the differentiation rate and was required for full differentiation into unilocular adipocytes. Significant activation of lipogenesis, i.e. lipid accumulation, by either insulin or oleic acid was monitored in times ranging from 1 to 24 h, depending on differentiation state, whereas significant effects on adipogenesis, i.e., surperimposed lipid accumulation and gene transcriptional regulations were measured after 3 to 4 d. Combination of selected times for analysis of lipid contents, cell counts, size fractionations, and gene transcriptional regulations showed that FAT/CD36 specific inhibitor AP5258 significantly increased cell survival of oleic acid-treated mouse and human adipocytes, and partially restored the transcriptional response to oleic acid in the presence of insulin through JNK pathway. Taken together, these data open new perspectives to study the molecular mechanisms commonly dysregulated in mouse and human obesity at the level of lipogenesis linked to hypertrophy and adipogenesis linked to hyperplasia. PMID- 26257991 TI - Optimization of in vitro cultivation strategies for human adipocyte derived stem cells. AB - With adipose-derived stem cells being in the focus of research in regenerative medicine, the need arises for fast reliable cultivation protocols. We have tested the cultivation of human adipose-derived stem cells in endothelial cell growth medium prior to induction and differentiation, against the long-established use of DMEM/F12 medium-based cultivation protocols. We found that cultivation in endothelial cell growth medium not only accelerates growth before induction and differentiation, but also allows shorter induction and differentiation times than those following precultivation with DMEM/F12 medium with regard to the formation of mature adipocytes and to the viability undifferentiated cells. These results were first observed morphologically but could be confirmed by performing adiponectin ELISA and cell proliferation assays. PMID- 26257992 TI - Glucose starvation and hypoxia, but not the saturated fatty acid palmitic acid or cholesterol, activate the unfolded protein response in 3T3-F442A and 3T3-L1 adipocytes. AB - Obesity is associated with endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) in adipose tissue. In this study we identify physiological triggers of ER stress and of the UPR in adipocytes in vitro. We show that two markers of adipose tissue remodelling in obesity, glucose starvation and hypoxia, cause ER stress in 3T3-F442A and 3T3-L1 adipocytes. Both conditions induced molecular markers of the IRE1alpha and PERK branches of the UPR, such as splicing of XBP1 mRNA and CHOP, as well as transcription of the ER stress responsive gene BiP. Hypoxia also induced an increase in phosphorylation of the PERK substrate eIF2alpha. By contrast, physiological triggers of ER stress in many other cell types, such as the saturated fatty acid palmitic acid, cholesterol, or several inflammatory cytokines including TNF-alpha, IL-1beta, and IL-6, do not cause ER stress in 3T3-F442A and 3T3-L1 adipocytes. Our data suggest that physiological changes associated with remodelling of adipose tissue in obesity, such as hypoxia and glucose starvation, are more likely physiological ER stressors of adipocytes than the lipid overload or hyperinsulinemia associated with obesity. PMID- 26257993 TI - Conditional immortalization of primary adipocyte precursor cells. AB - The production of new adipocytes requires the differentiation of adipocyte precursor (AP) cells residing within the adipose tissue stromal-vascular compartment. The objective was to obtain an immortalized primary adipogenic cell line derived from FACS isolated committed APs using the conditional expression of SV40 T antigen. Adipocyte precursors were isolated from white adipose tissue (WAT) using FACS to remove non-adipogenic cell populations from mice expressing a conditionally regulated SV40 T antigen. APs were maintained by continuous culture and induced to undergo adipogenic differentiation. Adipogenesis, determined by Oil Red O staining, was assessed with each passage and compared to wildtype controls. Adipogenic capability was rapidly lost with increased passage number in committed APs with concurrent reduction in cell proliferation and expression of essential late adipogenic genes, including Ppargamma and C/ebpalpha. Thus, FACS purified committed APs have limited capability to undergo expansion and subsequent adipogenic differentiation in vitro even if they are immortalized with the SV40 T antigen. PMID- 26257994 TI - Wt1, the mesothelium and the origins and heterogeneity of visceral fat progenitors. AB - One major gap in adipocyte biology has been a lack of understanding of the developmental origins of the different visceral white adipose tissue (WAT) depots and subcutaneous WAT. In a recent study we showed that most visceral WAT but no subcutaneous WAT arises from cells expressing the Wilms' tumor 1 (Wt1) gene late in mouse gestation.(1) Wt1 continues to be expressed in visceral WAT progenitors into adult life. We also showed that visceral WAT is lined by a mesothelium and provided evidence that this structure is the source of adipocytes. Our study also adds to the growing body of evidence that there is heterogeneity in the visceral progenitors, such that there are Wt1-expressing and non-expressing subsets, the relative proportions of which vary between depots. This raises the enticing prospect that the adipocytes arising from these progenitor subsets may have different properties and our preliminary data support this notion. Finally, evidence from our study and one from Spiegelman's group(2) suggests that Wt1 is not just a marker but regulates visceral WAT identity and the progenitor population. We discuss the implications of this work and some of the questions and future directions that arise from it. PMID- 26257995 TI - Role of microRNA biogenesis in adipocyte and lipodystrophy. AB - The detailed mechanism underlying adipocyte development and function remains to be fully understood. MicroRNAs are a class of non-coding regulators in adipocyte development and function in physiological and pathological conditions. Our recent study(11) using adipose-specific dgcr8 knockout mice demonstrates that microRNA biogenesis has a depot-specific function in adipose and plays an important role in brown adipocyte feature maintenance. Interestingly, in a parallel study from Kahn's group, Mori et al observed similar phenotypes in adipose-specific Dicer knockout mice. This study also reveals that the expression of Dicer is downregulated in the adipose from patients with HIV-associated lipodystrophy (HALS), suggesting that dysregulation of microRNA biogenesis may play a role in the onset of HALS. PMID- 26257996 TI - In this Issue of Adipocyte. PMID- 26257997 TI - Comparison of Three Parametric Models for Glaucomatous Visual Field Progression Rate Distributions. AB - PURPOSE: To compare parametric models for fitting published distributions of visual field progression rates (in dB/yr) for glaucoma. METHOD: We fitted a modified Gaussian model, a modified Cauchy model and a modified hyperbolic secant model to previously published distributions of visual field progression rates from Canada, Sweden, and the United States. The modification allowed the shape of the model's distribution either side of the mode to be independently varied to allow for the asymmetric tails seen in visual field progression rate distributions. RESULTS: Summing likelihoods across datasets, the modified hyperbolic secant was strongly favored (by 26.7 log units) compared with the next best-fitting model, the modified Cauchy. The modified hyperbolic secant was not the best fit for the Canadian dataset, however. Best-fitting modified hyperbolic secant parameters were broadly similarly between datasets, with parameter variances being less than those expected to negate the benefits of a previously described Bayesian method for improving individual visual field progression rate estimates in glaucoma. CONCLUSIONS: Although the optimum model differed depending upon the particular dataset, a modified hyperbolic secant performed well for all distributions investigated and was strongly favored when evidence was summed across datasets. TRANSLATIONAL RELEVANCE: Despite differences in the progression rate distributions between studies, the use of an "average" distribution may still be of benefit for improving individual visual field progression rate estimates in glaucoma using Bayesian methods. PMID- 26257999 TI - "Money talks. And the society we live in is very harsh." Cancer Care-Seeking from the Perspectives of Guam's Chamorros. AB - Cancer mortality is rising at an astonishing rate on the island of Guam compared to the US. The indigenous people of Guam, the Chamorro, suffer from the highest rates of cancer death compared to other ethnic groups. To better understand some of the factors underlying these mortality rates, in-depth interviews were conducted with 11 self-identified Chamorros of Guam to explore their experiences seeking screening and treatment for cancer. Respondent's care-seeking was significantly influenced by their family's wealth and their health insurance coverage. Informants who did not seek regular cancer screening reported financial barriers along with a lack of awareness of cancer screening. Immediate family members facilitated increased access to cancer care, but extended family members sometimes caused increased stress for participants with cancer. Public awareness campaigns promoting cancer screening need to be tied to structural changes to the health care system to make cancer care financially accessible for care-seekers. PMID- 26257998 TI - Characterizing the Impact of Off-Axis Scan Acquisition on the Reproducibility of Total Retinal Thickness Measurements in SDOCT Volumes. AB - PURPOSE: Off-axis acquisition of spectral domain optical coherence tomography (SDOCT) images has been shown to increase total retinal thickness (TRT) measurements. We analyzed the reproducibility of TRT measurements obtained using either the retinal pigment epithelium (RPE) or Bruch's membrane as reference surfaces in off-axis scans intentionally acquired through multiple pupil positions. METHODS: Five volumetric SDOCT scans of the macula were obtained from one eye of 25 normal subjects. One scan was acquired through a central pupil position, while subsequent scans were acquired through four peripheral pupil positions. The internal limiting membrane, the RPE, and Bruch's membrane were segmented using automated approaches. These volumes were registered to each other and the TRT was evaluated in 9 Early Treatment of Diabetic Retinopathy Study (ETDRS) regions. The reproducibility of the TRT obtained using the RPE was computed using the mean difference, coefficient of variation (CV), and the intraclass correlation coefficient (ICC), and compared to those obtained using Bruch's membrane as the reference surface. A secondary set of 1545 SDOCT scans was also analyzed in order to gauge the incidence of off-axis scans in a typical acquisition environment. RESULTS: The photoreceptor tips were dimmer in off-axis images, which affected the RPE segmentation. The overall mean TRT difference and CV obtained using the RPE were 7.04 +/- 4.31 MUm and 1.46%, respectively, whereas Bruch's membrane was 1.16 +/- 1.00 MUm and 0.32%, respectively. The ICCs at the subfoveal TRT were 0.982 and 0.999, respectively. Forty-one percent of the scans in the secondary set showed large tilts (> 6%). CONCLUSIONS: RPE segmentation is confounded by its proximity to the interdigitation zone, a structure strongly affected by the optical Stiles-Crawford effect. Bruch's membrane, however, is unaffected leading to a more robust segmentation that is less dependent upon pupil position. TRANSLATIONAL RELEVANCE: The way in which OCT images are acquired can independently affect the accuracy of automated retinal thickness measurements. Assessment of scan angle in a clinical dataset demonstrates that off-axis scans are common, which emphasizes the need for caution when relying on automated thickness parameters when this component of scan acquisition is not controlled for. PMID- 26258000 TI - An Abbreviated Impulsiveness Scale (ABIS) Constructed through Confirmatory Factor Analysis of the BIS-11. AB - Impulsiveness is a personality trait that reflects an urge to act spontaneously, without thinking or planning ahead for the consequences of your actions. High impulsiveness is characteristic of a variety of problematic behaviors including attention deficit disorder, hyperactivity, excessive gambling, risk-taking, drug use, and alcoholism. Researchers studying attention and self-control often assess impulsiveness using personality questionnaires, notably the common Barratt Impulsiveness Scale version 11 (BIS-11; last revised in 1995). Advances in techniques for producing personality questionnaires over the last 20 years prompted us to revise and improve the BIS-11. We sought to make the revised scale shorter - so that it would be quicker to administer - and better matched to current behaviors. We analyzed responses from 1549 adults who took the BIS-11 questionnaire. Using a statistical technique called factor analysis, we eliminated 17 questions that did a poor job of measuring the three major types of impulsiveness identified by the scale: inattention, spontaneous action, and lack of planning. We constructed our ABbreviated Impulsiveness Scale (ABIS) using the remaining 13 questions. We showed that the ABIS performed well when administered to additional groups of 657 and 285 adults. Finally, we showed expected relationships between the ABIS and other personality measurements related to impulsiveness, and showed that the ABIS can help predict alcohol consumption. We present the ABIS as a useful and efficient tool for researchers interested in measuring impulsive personality. PMID- 26258001 TI - Novel Approaches to Individual Alcohol Interventions for Heavy Drinking College Students and Young Adults. AB - Efficacious alcohol interventions for college students and young adults have been developed but produce small effects of limited duration. This paper provides a review and critique of novel (e.g., a significant deviation from a traditional, brief, and motivational intervention) interventions published between 2009 and 2014 to reduce alcohol use in this population and covers intervention format/components and efficacy on alcohol outcomes. We reviewed 12 randomized controlled trials of novel, individual-level alcohol interventions that reported alcohol outcomes. Four domains of novel interventions are discussed: content (e.g., pharmaco-therapy and automatic action tendency retraining), setting (e.g., health centers and ED), modality (e.g., mobile technology), and treatment integration. Findings were mixed for intervention efficacy to reduce amount and frequency of alcohol consumption. Few studies assessed impact on alcohol-related problems. Despite the prevalence of efficacious interventions, there is still an urgent need for novel treatment approaches and delivery mechanisms for this difficult-to-treat population. PMID- 26258002 TI - Drug Resistance in the Microaerophilic Parasite Giardia lamblia. AB - The microaerophilic parasite Giardia lamblia is a causative agent of dysentery affecting hundreds of millions of people around the globe every year. The symptoms of the disease, commonly referred to as giardiasis, are diarrhea, nausea, and malabsorption. Treatment of giardiasis is exclusively based on chemotherapy with antigiardial drugs, including metronidazole, albendazole, and nitazoxanide. In this review, all drugs currently used in the treatment of Giardia infections are discussed with a special emphasis on treatment failure and drug resistance. PMID- 26258003 TI - Hypersomnia in Mood Disorders: a Rapidly Changing Landscape. AB - Hypersomnia is commonly comorbid with depressive illness and is associated with treatment resistance, symptomatic relapse, and functional impairment. This review highlights recent changes in nosological classifications of hypersomnia. In addition, emergent findings regarding the neurobiologic underpinnings, assessment, and treatment of hypersomnia in mood disorders are reviewed, as well as the effects of hypersomnolence on illness course. Future strategies for research are proposed that may elucidate the causes of hypersomnia in mood disorders and lead to the development of improved diagnostic and therapeutic strategies. PMID- 26258004 TI - Interactions between the transmembrane domains of CD39: identification of interacting residues by yeast selection. AB - Rat CD39, a membrane-bound ectonucleoside triphosphate diphosphohydrolase that hydrolyzes extracellular nucleoside tri- and diphosphates, is anchored to the membrane by two transmembrane domains at the two ends of the molecule. The transmembrane domains are important for enzymatic activity, as mutants lacking one or both of these domains have a fraction of the enzymatic activity of the wild-type CD39. We investigated the interactions between the transmembrane domains by using a strain of yeast that requires surface expression of CD39 for growth. Random mutagenesis of selected amino acid residues in the N-terminal transmembrane domain revealed that the presence of charged amino acids at these positions prevents expression of functional protein. Rescue of the growth of these mutants by complementary mutations on selected residues of the C-terminal transmembrane domain indicates that there is contact between particular faces of the transmembrane domains. PMID- 26258005 TI - Looking back at ECSS 2014. AB - With the 2015 European College of Sports Science (ECSS) meeting in Malmo just around the corner (in time, if not space), I thought I would recap on what was an exciting meeting in Amsterdam last July. As Deputy Editor of a journal that, at the time, was yet to be launched - the 19th ECSS meeting provided the perfect place to make acquaintance with new and potential Editorial Board members and to get a feel for the research landscape. Despite the name, ECSS is an International organisation, and the delegation was truly global. Aside from Europe - Japan, Australasia and South Africa all seemed to be particularly well represented among delegates; not to mention, Aspetar, of Qatar, was a major sponsor of the event, and two exchange symposia were co-hosted between the ECSS and the American College of Sports Medicine (ACSM), and between ECSS and the Japanese Society of Physical Fitness & Sports Medicine (JSPFSM), respectively. The 4-day conference, held at the RAI Convention Centre, consisted of 4 plenary sessions and an honorary session, 36 invited symposia, 74 other oral sessions, 106 mini-oral sessions, and over 500 E-posters, covering the full gamut of sport and exercise science. As the programme's welcome message alluded to, I 'regretted that I had only two ears and two eyes'; however, in saying that, the vast coverage of the conference through social media provided one with no excuse for missing out on any information. PMID- 26258006 TI - Effect of Segment-Body Vibration on Strength Parameters. AB - BACKGROUND: In this study, we examine the biomechanical advantage of combining localized vibrations to hamstring muscles involved in a traditional resistance training routine. METHODS: Thirty-six male and female participants with at least 2 years of experience in resistance training were recruited from the German Sport University Cologne. The participants were randomized into two training groups: vibration training group (VG) and traditional training group (TTG). Both groups underwent a 4-week training phase, where each participant worked out at 70 % of the individual 1 repeat maximum (RM-maximum load capacity of a muscle for one lift to fatigue) (4 sets with 12 repetitions each). For participants in the VG group, local vibration was additionally applied directly to hamstring muscles during exercise. A 2-week examination phase preceded the pretests. After the pretests, the subjects underwent a prescribed training for 4 weeks. At the conclusion of the training, a 2-week detraining was imposed and then the study concluded with posttests and retest. RESULTS: The measured parameters were maximum isometric force of the hamstrings and maximum range of motion and muscle tension at maximum knee angle. The study revealed a significant increase in maximum isometric force in both training groups (VG = 21 %, TTG = 14 %). However, VG groups showed an increase in their range of motion by approximately 2 %. Moreover, the muscle tension at maximum knee angle increased less in VG (approximately 35 %) compared to TG (approximately 46 %). CONCLUSIONS: We conclude that segment-body vibrations applied in resistance training can offer an effective tool to increase maximum isometric force, compared to traditional training. The cause for these findings can be attributed to the additional local vibration stimulus. PMID- 26258007 TI - Spontaneous Entrainment of Running Cadence to Music Tempo. AB - BACKGROUND: Since accumulating evidence suggests that step rate is strongly associated with running-related injuries, it is important for runners to exercise at an appropriate running cadence. As music tempo has been shown to be capable of impacting exercise performance of repetitive endurance activities, it might also serve as a means to (re)shape running cadence. The aim of this study was to validate the impact of music tempo on running cadence. METHODS: Sixteen recreational runners ran four laps of 200 m (i.e. 800 m in total); this task was repeated 11 times with a short break in between each four-lap sequence. During the first lap of a sequence, participants ran at a self-paced tempo without musical accompaniment. Running cadence of the first lap was registered, and during the second lap, music with a tempo matching the assessed cadence was played. In the final two laps, the music tempo was either increased/decreased by 3.00, 2.50, 2.00, 1.50, or 1.00 % or was kept stable. This range was chosen since the aim of this study was to test spontaneous entrainment (an average person can distinguish tempo variations of about 4 %). Each participant performed all conditions. RESULTS: Imperceptible shifts in musical tempi in proportion to the runner's self-paced running tempo significantly influenced running cadence (p < .001). Contrasts revealed a linear relation between the tempo conditions and adaptation in running cadence (p < .001). In addition, a significant effect of condition on the level of entrainment was revealed (p < .05), which suggests that maximal effects of music tempo on running cadence can only be obtained up to a certain level of tempo modification. Finally, significantly higher levels of tempo entrainment were found for female participants compared to their male counterparts (p < .05). CONCLUSIONS: The applicable contribution of these novel findings is that music tempo could serve as an unprompted means to impact running cadence. As increases in step rate may prove beneficial in the prevention and treatment of common running-related injuries, this finding could be especially relevant for treatment purposes, such as exercise prescription and gait retraining. KEY POINTS: Music tempo can spontaneously impact running cadence.A basin for unsolicited entrainment of running cadence to music tempo was discovered.The effect of music tempo on running cadence proves to be stronger for women than for men. PMID- 26258008 TI - Chemoresistance, cancer stem cells, and miRNA influences: the case for neuroblastoma. AB - Neuroblastoma is a type of cancer that develops most often in infants and children under the age of five years. Neuroblastoma originates within the peripheral sympathetic ganglia, with 30% of the cases developing within the adrenal medulla, although it can also occur within other regions of the body such as nerve tissue in the spinal cord, neck, chest, abdomen, and pelvis. MicroRNAs (miRNAs) regulate cellular pathways, differentiation, apoptosis, and stem cell maintenance. Such miRNAs regulate genes involved in cellular processes. Consequently, they are implicated in the regulation of a spectrum of signaling pathways within the cell. In essence, the role of miRNAs in the development of cancer is of utmost importance for the understanding of dysfunctional cellular pathways that lead to the conversion of normal cells into cancer cells. This review focuses on highlighting the recent, important implications of miRNAs within the context of neuroblastoma basic research efforts, particularly concerning miRNA influences on cancer stem cell pathology and chemoresistance pathology for this condition, together with development of translational medicine approaches for novel diagnostic tools and therapies for this neuroblastoma. PMID- 26258009 TI - Isolation and time lapse microscopy of highly pure hepatic stellate cells. AB - Hepatic stellate cells (HSC) are the main effector cells for liver fibrosis. We aimed at optimizing HSC isolation by an additional step of fluorescence-activated cell sorting (FACS) via a UV laser. HSC were isolated from livers of healthy mice and animals subjected to experimental fibrosis. HSC isolation by iohexol- (Nycodenz) based density centrifugation was compared to a method with subsequent FACS-based sorting. We assessed cellular purity, viability, morphology, and functional properties like proliferation, migration, activation marker, and collagen expression. FACS-augmented isolation resulted in a significantly increased purity of stellate cells (>99%) compared to iohexol-based density centrifugation (60-95%), primarily by excluding doublets of HSC and Kupffer cells (KC). Importantly, this method is also applicable to young animals and mice with liver fibrosis. Viability, migratory properties, and HSC transdifferentiation in vitro were preserved upon FACS-based isolation, as assessed using time lapse microscopy. During maturation of HSC in culture, we did not observe HSC cell division using time lapse microscopy. Strikingly, FACS-isolated, differentiated HSC showed very limited molecular and functional responses to LPS stimulation. In conclusion, isolating HSC from mouse liver by additional FACS significantly increases cell purity by removing contaminations from other cell populations especially KC, without affecting HSC viability, migration, or differentiation. PMID- 26258010 TI - MMP-2 and MMP-9 activities and TIMP-1 and TIMP-2 expression in the prostatic tissue of two ethanol-preferring rat models. AB - We investigated whether chronic ethanol intake is capable of altering the MMP-2 and MMP-9 activities and TIMP-2 and TIMP-1 expression in the dorsal and lateral prostatic lobes of low (UChA) and high (UChB) ethanol-preferring rats. MMP-2 and MMP-9 activities and TIMP-1 and TIMP-2 expression were significantly reduced in the lateral prostatic lobe of the ethanol drinking animals. Dorsal prostatic lobe was less affected showing no significant alterations in these proteins, except for a reduction in the TIMP-1 expression in UChA rats. These important findings demonstrate that chronic ethanol intake impairs the physiological balance of the prostate extracellular matrix turnover, through downregulation of MMPs, which may contribute to the development of prostatic diseases. Furthermore, since these proteins are also components of prostate secretion, the negative impact of chronic ethanol intake on fertility may also involve reduction of MMPs and TIMPs in the seminal fluid. PMID- 26258012 TI - Therapeutic Process During Exposure: Habituation Model. AB - The current paper outlines the habituation model of exposure process, which is a behavioral model emphasizing use of individually tailored functional analysis during exposures. This is a model of therapeutic process rather than one meant to explain the mechanism of change underlying exposure-based treatments. Habitation, or a natural decrease in anxiety level in the absence of anxiety-reducing behavior, might be best understood as an intermediate treatment outcome that informs therapeutic process, rather than as a mechanism of change. The habituation model purports that three conditions are necessary for optimal benefit from exposures: 1) fear activation, 2) minimization of anxiety-reducing behaviors, and 3) habituation. We describe prescribed therapist and client behaviors as those that increase or maintain anxiety level during an exposure (and therefore, facilitate habituation), and proscribed therapist and client behaviors as those that decrease anxiety during an exposure (and therefore, impede habituation). We illustrate model-consistent behaviors in the case of Monica, as well as outline the existing research support and call for additional research to further test the tenets of the habituation model as described in this paper. PMID- 26258011 TI - Insulin-like growth factor and epidermal growth factor signaling in breast cancer cell growth: focus on endocrine resistant disease. AB - Breast cancer is the most common type of cancer for women worldwide with a lifetime risk amounting to a staggering total of 10%. It is well established that the endogenous synthesis of insulin-like growth factor (IGF) and epidermal growth factor (EGF) polypeptide growth factors are closely correlated to malignant transformation and all the steps of the breast cancer metastatic cascade. Numerous studies have demonstrated that both estrogens and growth factors stimulate the proliferation of steroid-dependent tumor cells, and that the interaction between these signaling pathways occurs at several levels. Importantly, the majority of breast cancer cases are estrogen receptor- (ER-) positive which have a more favorable prognosis and pattern of recurrence with endocrine therapy being the backbone of treatment. Unfortunately, the majority of patients progress to endocrine therapy resistant disease (acquired resistance) whereas a proportion of patients may fail to respond to initial therapy (de novo resistance). The IGF-I and EGF downstream signaling pathways are closely involved in the process of progression to therapy resistant disease. Modifications in the bioavailability of these growth factors contribute critically to disease progression. In the present review therefore, we will discuss in depth how IGF and EGF signaling participate in breast cancer pathogenesis and progression to endocrine resistant disease. PMID- 26258014 TI - Temporo-mandibular joint ankylosis - The difficult airway. PMID- 26258013 TI - Ubiquitin is a versatile scaffold protein for the generation of molecules with de novo binding and advantageous drug-like properties. AB - In the search for effective therapeutic strategies, protein-based biologicals are under intense development. While monoclonal antibodies represent the majority of these drugs, other innovative approaches are exploring the use of scaffold proteins for the creation of binding molecules with tailor-made properties. Ubiquitin is especially suited for this strategy due to several key characteristics. Ubiquitin is a natural serum protein, 100% conserved across the mammalian class and possesses high thermal, structural and proteolytic stability. Because of its small size and lack of posttranslational modifications, it can be easily produced in Escherichia coli. In this work we provide evidence that ubiquitin is safe as tested experimentally in vivo. In contrast to previously published results, we show that, in our hands, ubiquitin does not act as a functional ligand of the chemokine receptor CXCR4. Cellular assays based on different signaling pathways of the receptor were conducted with the natural agonist SDF-1 as a benchmark. In none of the assays could a response to ubiquitin treatment be elicited. Furthermore, intravenous application to mice at high concentrations did not induce any detectable effect on cytokine levels or hematological parameters. PMID- 26258015 TI - Saliva as a prediction tool for dental caries: An in vivo study. AB - INTRODUCTION: The present study was undertaken to assess the caries activity by comparing the pH, buffering capacity, calcium, phosphorous, amylase along with the association of mutans in saliva for caries-free and caries-active children and to find out the interrelationship amongst the two groups. METHODOLOGY: The study sample of 80 children, aged between 4 and 8 years were included in the study. Caries status of each child was recorded using DMFS. They were divided into two groups: (i) caries-free group (40) and (ii) caries-active group (40). After collecting the salivary samples, mutans were determined using Saliva-Check mutans kit and buffering capacity by Saliva-Check Buffer kit. The remaining samples were sent to laboratory for analyzing pH by electrode pH meter, calcium by OCPC(o-cresolphthalein complexone) photometric method, phosphorous by phosphomolybdate/UV method, amylase by CNP-G3(2chloro-4-nitrophenyl-alpha maltotrioside) method using semi-autoanalyzer. RESULTS: The results obtained were tabulated and subjected to statistical analysis. The pH, buffering capacity, calcium and phosphorous level were found to be increased with the decrease in the caries activity of the children whereas amylase activity was increased with the increase in caries activity. It was observed that 77.5% children were tested positive and 22.5% were tested negative for mutans in caries-active group whereas 100% children were tested negative for mutans in caries-free group. CONCLUSION: The physicochemical properties of saliva, such as pH, buffering capacity, calcium, phosphorous, amylase and Streptococcus mutans has a definite relationship with caries activity. PMID- 26258016 TI - Neurosensory disturbance after bilateral sagittal split osteotomy: A retrospective study. AB - AIM: To retrospectively evaluate neurosensory disturbance (NSD) after bilateral sagittal split osteotomy (BSSO). MATERIAL AND METHODS: A retrospective review was carried out to assess inferior alveolar nerve function in patients treated by BSSO from 2010 to 2013. All patients included in the study were assessed using objective (cotton swabs and pin prick testing) and subjective testing (questionnaire) for inferior alveolar nerve function after a minimum of 1 year of follow-up. Medical records of the patients were used to assess the incidence of NSD in the immediate post-operative period. RESULTS: 15 patients (30 sides) had undergone BSSO during the specified time period. On subjective testing, NSD was reported in 22 operated sides (73.3%) in the immediate post-operative period, while 4 operated sides (13.3%) reported persistent NSD. On objective testing, immediate post-operative NSD was seen in 20 operated sides (66.7%). After a minimum of 1 year follow-up, recovery was seen in 18 operated sides while persistent NSD was seen in 2 operated sides (6.7%). CONCLUSION: NSD of the inferior alveolar nerve is a common complication after BSSO in the immediate post operative period. However in a long term, nerve function usually recovers. PMID- 26258017 TI - Comparative evaluation of healing after gingivectomy with electrocautery and laser. AB - PURPOSE OF THE STUDY: To evaluate whether laser has got any advantage over electrocautery in performing gingivectomy procedure. METHOD: This was randomized split mouth prospective study where 17 patients having symmetrical gingival hyperplasia were treated with electrocautery and laser on each side. Intra- and postoperative parameters assessed were duration of surgery, bleeding, tissue sticking, postoperative pain and healing. The results were statistically analyzed and compared. RESULT: There were 7 Females and 10 Males with a mean age of 28.2 +/- 11.6 years. The mean time taken on the laser and electrocautery was 16 (+/ 8.05) and 16.7 min (+/-9.86) respectively and the difference was not significant. On laser side, there was no bleeding in 3 (17.6%) and self limiting in 14 patients (82.4%) whereas electrocautery side, there was no bleeding in 2 (11.8%) and self limiting in 15 patients (88.2%). Both electrocautery and laser were comparable regarding ease of use during gingivectomy procedure. Charring was observed on both sides although there was more charring on the laser side. Fibrinous slough was present on both sides at 24 h. Difference in healing was not significant at various time intervals. There were no significant difference in postoperative pain experienced by the patients among the laser and cautery group at different time intervals. CONCLUSION: Both techniques with proper adhesion to safeguards, can be used to remove gingival overgrowth with equal efficiency and wound healing capacity. There is no advantage of diode laser over electrocautery in performing gingivectomy. PMID- 26258018 TI - Custom made orthotic device for maintaining skull architecture during the postoperative period in infants undergoing craniosynostosis surgery. AB - AIM: To fabricate a cost effective, indigenous and simple orthotics helmet for post-operative cranial molding in patients with craniosynostosis surgery. METHODS: We present a case of 15 month old infant with secondary cranial vault deformity. Cranial vault remodeling surgery involving the posterior skull was planned and executed to increase the posterior gap, so that brain growth would be facilitated towards this empty space. Materials such as thermoplastic sponge, thermoplastic ionomer resin sheet, soft sponge and Velcro straps are used to fabricate a cranial orthotics helmet. RESULTS: We have successfully used the above materials to fabricate the orthotics helmet for post-operative cranial molding. CONCLUSION: The technique described in this article is simple and cost effective. It can be custom made according to the demands of the surgical technique and the type of synostosis. It favors an individualistic prognosis, and proves worthwhile as every synostosis requires a unique treatment plan. It is an excellent adjuvant to craniosynostosis remodeling surgery. PMID- 26258019 TI - Are salivary amylase and pH - Prognostic indicators of cancers? AB - BACKGROUND: Saliva, "Mirror of body's health" has long been of particular interest as a substitute for blood for disease diagnosis and monitoring. The radiation effects on salivary glands are of particular interest in which salivary amylase is a good indicator of salivary glands function. Thus, estimation of these parameters represents a reasonable approach in evaluation of patient's risk for disease occurrence, intensity and prognosis. AIM OF STUDY: To evaluate and compare the pH and amylase levels in saliva of cancer patients prior to treatment, patients during treatment. MATERIALS AND METHODS: Saliva samples of 90 individuals were taken which were divided into 3 groups - 30 individuals without cancer, 30 cancer patients prior treatment and 30 cancer patients during treatment. Materials used were pH strips and pH meter, Salivary Amylase assay. RESULTS: Statistical analysis - ANOVA with post-hoc Tukey's test. 1) Significant decrease in salivary amylase levels - in cancer patients, during treatment when compared to others. 2) Significant decrease in salivary pH levels in newly diagnosed cancer patients prior to treatment. CONCLUSION: To conclude, pH strips and pH meter showed to be a useful tool in the measurement of pH of saliva in individuals with and without cancer. This study showed that cancer patients without treatment have a lower pH of saliva. Treatment increased the pH of the saliva to a more alkaline level whereas amylase levels decreased in those subjects. Therefore those parameters can be an area of further research with an increased sample size, which in-turn may help in opening the doors for new dimension in non invasive prognostic markers. PMID- 26258021 TI - Tentpole technique for bone regeneration in vertically deficient alveolar ridges: A review. AB - BACKGROUND AND OBJECTIVES: Vertical augmentation is necessary in cases of extensive resorption of alveolar ridge for dental implants placement and esthetic prosthetic rehabilitation. Several surgical techniques have been used to increase bone height including distraction osteogenesis, and particulate or block bone graft. This study was done to describe the evolution of "tentpole technique" and to review the literature related to this technique and thus evaluate its effectiveness to augment large vertical alveolar ridge defects for implant placement. MATERIAL AND METHODS: The evidence was obtained by PubMed and Google search using key words: tentpole technique, ridge resorption, and alveolar ridge augmentation . The years of search included from 2002 till 2013. RESULTS: The technique was described as effective on review of outcome of existing studies. It was found that considerable and stable increase in alveolar ridge height was achieved using tentpole technique. CONCLUSIONS: Tenting of periosteum and soft tissue matrix maintains space and enhances the effectiveness of bone graft. This technique offers predictable functional and esthetic reconstruction of large vertical alveolar defects. PMID- 26258022 TI - A rare case report of Ellis Van Creveld syndrome in an Indian patient and literature review. AB - Ellis Van Creveld syndrome (EVC) is a rare genetic disorder having autosomal recessive inheritance affecting the Amish population of Pennsylvania in USA with incidence of 1:244,000 for the general population. This syndrome consists of characteristic features such as bilateral postaxial polydactyly, chondroectodermal dysplasia, congenital heart defects and hypoplastic nails and teeth. There are few case reports of this syndrome reported in dental literature. We report a case of a 17 year old female presenting typical features of this syndrome and the oral findings of this patient which are the key diagnostic features. PMID- 26258020 TI - Genomic expression in non syndromic cleft lip and palate patients: A review. AB - Cleft lip and palate are common congenital anomalies with significant medical, psychological, social, and economic ramifications, affecting one in seven hundred live births. Genetic causes of non syndromic cleft lip and/or palate (NSCLP) include chromosomal rearrangements, genetic susceptibility to teratogenic exposures, and complex genetic contributions of multiple genes. Development of the orofacial clefts in an individual will depend on the interaction of several moderately effecting genes with environmental factors. Several candidate genes have been genotyped in different population types, using case parent trio or case control design; also genes have been sequenced and SNPs have been reported. Quantitative and molecular analysis have shown linkage and association studies to be more relevant. Recent literature search shows genome wide association studies using microarray. The aim of this paper was to review the approaches to identify genes associated with NSCLP and to analyze their differential expressions. Although no major gene has been confirmed, a lot of research is ongoing to provide an understanding of the pathophysiology of the orofacial clefts. PMID- 26258023 TI - Progressive facial asymmetry resulting from condylar osteochondroma - A case report detailing the resection, subsequent orthognathic intervention and custom joint replacement. AB - We discuss a 37 year old male - who presented with marked facial asymmetry and signs/symptoms suggestive of condylar hyperplasia. Imaging confirmed a large exophytic growth arising from the right mandibular condylar head. Treatment included tumour resection, orthognathic intervention and total joint replacement. The clinical presentation, pathology and treatment, along with a brief discussion are described in this report. PMID- 26258024 TI - Orodental manifestations in cases with partial agenesis of corpus callosum-rare phenomena. AB - This article focuses on the associated signs and symptoms of patients with partial agenesis of the corpus callosum. The orodental manifestations of such cases have been given special weightage which will prove to be of great help to oral physician when encountered with such cases. CASE DETAILS: Two siblings, aged 14 and 16 years, reported with a chief complaint of severe crowding of teeth with mouth breathing habit. They were low birth-weight babies and had been born to non consanguinous parents. The distinguishing features of these children were craniofacial abnormalities, delayed developmental milestones, mild mental retardation and abnormal gait. The nosological features and the clinical manifestations of this syndrome and the plausible autosomal recessive inheritance of this rare syndrome have been elicited. The diagnosis was based on characteristic phenotype, in particular striking craniofacial and skeletal abnormalities and neuroimaging. CONCLUSION: It is a challenge for healthcare professionals to help these youths to maximize their potential as human beings and help them achieve a meaningful adulthood. On the other hand, diagnosing such cases can be a challenge to dentistry. A systematic protocol, if adhered, can lead to a more appropriate diagnosis. Managing such cases in a clinical setup involves a multispeciality and interdisciplinary approach. PMID- 26258025 TI - Solitary fibrous tumor of the nasal cavity and paranasal sinuses: A case report. AB - Solitary Fibrous Tumors (SFT) are rare neoplasms first described in 1931 by Klemperer and Rabin. SFT's have mesenchymal rather than mesothelial origin. They arise mostly from serous membranes, although they also originate in other regions such as: the urogenital system, mediastinal space, lungs, vulva, orbit, thyroid, nasopharyngeal region, larynx, salivary glands. SFT of the nasal cavity and paranasal sinuses are extremely rare. To the year 2014 only 33 cases were reported in English literature. PATIENTS AND METHODS: We present a case of 58 year-old man with solitary fibrous tumor localized in the right nasal cavity. The patient presented with an 18-month history of epistaxis and right epiphora. He also reported unilateral right-sided nasal obstruction over the last 6 months. RESULTS: CT disclosed a large, homogeneous mass in the nasal cavity infiltrating and destroying nasal septum, turbinates, occupying right maxillary sinus, right ethmoid, extending to the right frontal sinus and right orbit. The infiltration of the right oculus was suspected. Biopsy revealed fibrocytes and histiocytes proliferation with rich vascularization. There was no evidence of histological malignancy. Pathology results were significant for SFT. CONCLUSION: The tumor was excised by means of right lateral rhinotomy. Neither the extension to the right maxillary sinus nor the orbital floor infiltration was seen intraoperatively despite the fact, that it was observed in computed tomography before the surgery. The patient had a 5.5-year follow up after surgery, radiological examination showed no recurrence. PMID- 26258026 TI - Use of a light cured periodontal surgical dressing material in temporization: A convenient approach. AB - Majority of provisional restorations are fabricated directly in the mouth. However, there are several reasons where the direct technique may not be feasible and the clinician might need an indirect method. This report describes the use of a periodontal surgical dressing material (PSD) as a quick solution in such situations, utilizing it for short term temporization till the indirect provisional is fabricated. PSD's may be used for short term temporization in cases where the need of indirect temporization requires a patient to go without a provisional for a few days or the definitive restoration can be delivered in a very short span of time. It also opens up the possibility of single sitting abutment reduction at the time of periodontal surgery, using the pack for a dual purpose-healing & temporization. PMID- 26258027 TI - Post-Odontoma autotransplantation of an impacted tooth: A case report. AB - After years of relegation by dental implants, autotransplantation has recently become more popular because of a better understanding of its science. The prognosis of autotransplantation primarily depends upon the presence of an intact alveolar bone at the transplant site and the regeneration of a functional periodontal ligament of the transplant. Replacement of an unsalvaged or a missing tooth by a natural tooth with normal periodontium within a short duration of treatment is the ultimate challenge of autotransplantation. Meanwhile, Platelet Rich Fibrin (PRF) is popular as a biomaterial which helps in the regeneration of bone and periodontal tissues. To improve the prognosis, and also shorten the treatment time in a rare case of autotransplantation of an impacted tooth in a post-odontoma site, we did a two-stage surgical procedure aided by synthetic bone granules (Biograft) and PRF. The clinical and radiological findings at 6 months follow-up showed good result and promise. PMID- 26258028 TI - The midfacial glomangiopericytoma - Case report. AB - Glomangiopericytoma is classified as a borderline low malignancy tumor but recurrence rate is reported to be about 16.8%-30%, probably caused by the lack of radical resection.(1) It is a rare tumor arising from pericytes surrounding capillaries. The tumor has a predilection for the nasal cavity and paranasal sinuses. We report a case of glomangiopericytoma with an aim to present how it can invade and destroy both maxillary bones and lower part of nasal cavity. Due to its dimensions the tumor required extensive resection within tumor-free margins. On the basis of immunohistochemical staining the tumor was diagnosed as glomangiopericytoma. Strict follow-up of 16 months after radical resection revealed no recurrence of the tumor. PMID- 26258029 TI - Hospital costs in the US for pulmonary mycobacterial diseases. AB - BACKGROUND: Pulmonary mycobacterial diseases describe both tuberculosis (TB) and nontuberculous mycobacteria (NTM). Few data are available measuring the cost burden of mycobacterial diseases at the national level. The purpose of this study is to evaluate the cost burden and measure emerging trends in hospitalization of pulmonary TB and NTM cases in the United States from 2001 through 2012. METHODS: This study is a retrospective, community-based cost analysis of hospitalized patients with a principal diagnosis of pulmonary mycobacterial diseases from 2001 through 2012. Data for pulmonary TB and NTM were retrieved from the Healthcare Cost and Utilization Project (HCUP), US Department of Health and Human Services. The statistical significance of observed trends of NTM and TB national hospital costs was calculated using Poisson log-linear regression. RESULTS: 20,049 hospital discharges were reported for pulmonary NTM and 69,257 for pulmonary TB in the US from 2001 through 2012. The total associated cost of these discharges was $903,767,292 for pulmonary NTM and $2,078,113,317 for pulmonary TB. During the study period, the national hospital costs of pulmonary NTM increased at a statistically significant rate in the US over each year (P = 0.001). However, no such increase was found for national hospital costs of pulmonary TB. CONCLUSIONS: The national hospital cost of NTM management is increasing. These results emphasize the importance of continued research in pulmonary NTM in order to improve current guidelines in prevention and treatment strategies. PMID- 26258030 TI - The Simple Cow Hitch Stitch Technique for Arthroscopic Rotator Cuff Repair and Stabilization Using Knotless Suture Anchors. AB - The tissue-suture interface is the most vulnerable and challenging part of adequate restoration and fixation in rotator cuff repair. We describe a simple stitch technique for arthroscopic rotator cuff repair using knotless suture anchors based on the cow hitch. The simple cow hitch stitch technique is easy to perform, especially under difficult conditions, and provides excellent initial fixation strength as required for integration of the reinserted cuff and for shoulder stabilization. PMID- 26258031 TI - Dry Endoscopic-Assisted Mini-Open Approach With Neuromonitoring for Chronic Hamstring Avulsions and Ischial Tunnel Syndrome. AB - Chronic hamstring origin avulsions and ischial tunnel syndrome are common causes of posterior hip pain. Although physical therapy has shown benefits in some cases, recent evidence has reported better outcomes with surgical treatment in appropriately selected patients. The full-open approach has been the classic procedure to address this problem. However, the complications related to extensive tissue exposure and the proximity of the incision to the perianal zone have led to the description of full-endoscopic techniques. Achieving an accurate hamstring repair could be technically demanding with a full-endoscopic procedure. Accurate reattachment is crucial in hamstring repair because of the functional demand of the muscles crossing of 2 major joints (hip and knee). This surgical note describes a mixed technique including a mini-open approach, neuromonitoring, and dry endoscopic-assisted repair of the hamstring origin as an alternative for treating patients with chronic hamstring avulsions and ischial tunnel syndrome that remain symptomatic despite nonoperative treatment. PMID- 26258032 TI - Lateral Decubitus All-Arthroscopic Latarjet Procedure for Treatment of Shoulder Instability. AB - Shoulder instability can be a challenging condition to treat when it becomes refractory to soft-tissue procedures or when bone loss exceeds 25% to 27% of the glenoid. The Bristow-Latarjet procedure has been developed and popularized to deal with these concerns. Traditionally, the procedure has been performed as an open approach; however, this has been recently supplanted by novel arthroscopic techniques. We present a technique for the procedure performed with the patient in a semi-lateral decubitus position that assists with optimal graft placement on the native glenoid. We use the cannulated Bristow-Latarjet Instability Shoulder System (DePuy Mitek, Raynham, MA). After a diagnostic arthroscopic evaluation, we use multiple arthroscopic anterior portals to debride the rim of the glenoid. The coracoid is prepared and taken down arthroscopically, and the cannulated guide is attached and advanced through an arthroscopically created subscapularis split. With the shoulder held in a reduced position, we are then able to drill and anchor the graft to the native glenoid. The patient is able to begin gentle range of-motion exercises immediately postoperatively. PMID- 26258033 TI - Arthroscopic Correction of a Supracondylar Malunion in a Child. AB - Malunions are a well-recognized complication of pediatric supracondylar humeral fractures. Results of corrective osteotomies vary, and complication rates have been reported to be as high as 40%. Considering the high rate of complications for malunion correction, we investigated the feasibility of arthroscopy. We present a technique for arthroscopic supracondylar osteotomy and percutaneous pinning. There are many advantages of an arthroscopic approach to malunion correction, including extension-type deformity correction, safe access to the anterior humerus, and minimal dissection and scarring; any intracapsular contracture can be addressed as well. Elbow arthroscopy appears to be a viable option in the pediatric orthopaedic surgeon's armamentarium. PMID- 26258034 TI - Direct "Cystoscopic" Approach for Arthroscopic Decompression of an Intraosseous Ganglion of the Lunate. AB - Intraosseous ganglion cysts (IOGs) are uncommon lesions of the carpal bones and can present with persistent pain and stiffness of the wrist. Surgical decompression is recommended, and a variety of approaches to decompress symptomatic IOGs of the wrist have been described. We describe an arthroscopic approach that can be performed with only 2 portals and offers excellent access for visualization and instrumentation. The procedure involves creating a 3.2-mm tunnel into the lunate cyst; this is performed through the dorsal non-articular surface of the lunate, under direct vision, and the position is confirmed with fluoroscopy. A 2.4-mm arthroscope is passed through the drill hole, and a direct "cystoscopic" view of the IOG is obtained. Biopsy of the cyst contents is performed under direct vision, and small-joint shavers and burrs are used for effective debridement. Advantages of this technique are actual visualization of the pathology, complete intracystic debridement, and simultaneous treatment of any coexistent intra-articular pathology. In addition, the minimal 3.2-mm lunate tunnel access maintains the structural integrity of the lunate and reduces the need for additional bone graft supplementation. PMID- 26258035 TI - Arthroscopic Suture Fixation in Femoral-Sided Avulsion Fracture of Anterior Cruciate Ligament. AB - A femoral-sided avulsion fracture of the anterior cruciate ligament (ACL) is a rare and challenging condition. Most reported cases have occurred in childhood or adolescence. Many techniques of ACL repair have been reported, and in recent years, techniques in arthroscopic surgery have been developed and have become ever more popular with orthopaedic surgeons. We created a technique of arthroscopic ACL repair with suture anchor fixation for a femoral-sided ACL avulsion fracture. This technique saves the natural ACL stump. It is available for cases in which creation of a tibial tunnel is not allowed. Moreover, it does not require a skin incision for fixation on the far femoral cortex and, therefore, does not require a second operation to remove the fixation device. The arthroscopic technique also has a good cosmetic outcome. PMID- 26258036 TI - Arthroscopic Visualization of Abnormal Movement of Discoid Lateral Meniscus With Snapping Phenomenon. AB - Discoid lateral meniscus with snapping phenomenon is a rare pathologic condition. The purpose of this article is to present an arthroscopic technique for the treatment of discoid lateral meniscus with snapping phenomenon. The patient is placed in the supine position for confirmation of snapping. As the patient's knee bends, it can be confirmed by arthroscopy that the posterior horn of the discoid lateral meniscus moves posteriorly and the central portion of the discoid lateral meniscus moves anteriorly at the same time with snapping at deep flexion angles. The anterior segment of the discoid lateral meniscus is found to be redundant and is often folded. On the contrary, as the patient's knee extends, the central portion is returned to the original position accompanied by snapping at nearly full extension. After excision of the central portion, the movement of the meniscus is evaluated again and the disappearance of the snapping phenomenon can be confirmed. Although it includes limitations, this application is easy and would certainly help surgeons to treat snapping knee with discoid lateral meniscus. PMID- 26258037 TI - Combined Intra- and Extra-articular Reconstruction of the Anterior Cruciate Ligament: The Reconstruction of the Knee Anterolateral Ligament. AB - We present a new technique for the combined intra- and extra-articular reconstruction of the anterior cruciate ligament. Intra-articular reconstruction is performed in an outside-in manner according to the precepts of the anatomic femoral tunnel technique. Extra-articular reconstruction is performed with the gracilis tendon while respecting the anatomic parameters of the origin and insertion points and the path described for the knee anterolateral ligament. PMID- 26258038 TI - Deep Transverse Lateral Retinaculum Reconstruction for Medial Patellar Instability. AB - Medial patellar instability can be a disabling complication of an extensive lateral retinaculum release. It is often overlooked, and for the diagnosis, it is necessary to have a high index of suspicion. Typically, the patient feels a new pain and new instability after the lateral retinaculum release that are distinct from, and much worse than, those before surgery. All of our patients had significant relief from their pain with "reverse" McConnell taping. If there is a significant improvement in symptoms after this taping and stress radiographs or stress axial computed tomography scans show an objective pathologic medial patellar displacement, reconstruction of the lateral retinaculum should be considered. This article details our technique for reconstruction of the deep transverse layer of the lateral retinaculum using an anterior strip of the iliotibial band. This strip is detached from its insertion onto the Gerdy tubercle and then reflected proximally beyond the level of the lateral femoral epicondyle. Finally, it is attached either by direct suture to the remaining prepatellar and peripatellar retinaculum if there is adequate tissue present or by a suture anchor. PMID- 26258039 TI - Endoscopic Pubic Symphysectomy for Athletic Osteitis Pubis. AB - Osteitis pubis is a common form of athletic pubalgia associated with femoroacetabular impingement. Endoscopic pubic symphysectomy was developed as a less invasive option than open surgical curettage for recalcitrant osteitis pubis. This technical note demonstrates the use of the anterior and suprapubic portals in the supine lithotomy position for endoscopic burr resection of pubic symphyseal fibrocartilage and hyaline endplates. Key steps include use of the suprapubic portal for burr resection of the posteroinferior symphysis and preservation of the posterior and arcuate ligaments. Endoscopic pubic symphysectomy is a minimally invasive bone-conserving surgery that retains stability and may be useful in the treatment of recalcitrant osteitis pubis or osteoarthritis. It nicely complements arthroscopic surgery for femoroacetabular impingement and may find broader application in this group of co-affected athletes. PMID- 26258040 TI - All-Arthroscopic Autologous Matrix-Induced Chondrogenesis for the Treatment of Osteochondral Lesions of the Talus. AB - Several surgical techniques have been described for the treatment of talar chondral lesions. Among them, microfracture is well established. Autologous matrix-induced chondrogenesis (AMIC), using microfracture and biomaterials, has shown promising results for the treatment of knee osteochondral lesions and has been proposed for the ankle as an open technique. We describe an all-arthroscopic AMIC technique. The benefits of an all-arthroscopic procedure include smaller incisions with less soft-tissue dissection, better visualization of the joint, and a quicker recovery compared with open surgery. The use of matrix to support cartilage regeneration promotes good-quality cartilage tissue with satisfactory long-term outcomes. Our all-arthroscopic AMIC technique uses a type I-type III porcine collagen matrix (Chondro-Gide; Geistlich Pharma, Wolhusen, Switzerland) and is characterized by 2 different arthroscopic surgical phases. First, adequate exposure is achieved through use of a Hintermann spreader (Integra LifeSciences, Plainsboro, NJ) with sufficient joint distraction and wet lesion preparation. The second surgical step is performed dry, involving matrix placement and fixation. The all-arthroscopic AMIC technique for the treatment of osteochondral lesions of the talus allows a very precise reconstruction in the case of cartilage defects and avoids the need for a more invasive operation associated with higher morbidity and a longer surgical time. PMID- 26258041 TI - A Technique of Superficial Medial Collateral Ligament Reconstruction Using an Adjustable-Loop Suspensory Fixation Device. AB - This report describes superficial medial collateral ligament reconstruction of the knee using a novel method of graft fixation with the ACL Tightrope RT (Arthrex, Naples, FL). After tibial fixation with either a standard interference screw or staple, femoral fixation of the semitendinosus tendon is performed with the adjustable-loop suspensory fixation device, which allows for both initial graft tensioning and re-tensioning after cyclical knee range of motion. This provides the ability for the graft to accommodate for resultant soft-tissue creep and stress relaxation, thereby allowing for optimal soft-tissue tension and reduction in laxity at the end of the procedure. PMID- 26258042 TI - Knotless Arthroscopic Repair of Subscapularis Tendon Tears Using Looped Suture. AB - Subscapularis tendon tears present a technical challenge because both diagnosis and arthroscopic treatment can be difficult. One difficulty is the limited visualization and working space of the anterior shoulder. Although most tears of the subscapularis are partial- or full-thickness tears of the upper third of the tendon, occasionally, larger or more retracted tears are encountered. Various techniques have been developed to treat a wide variety of tear patterns. We present a simple technique using a looped suture that remains easy to use in the limited working space of the anterior shoulder; can be easily modified to accommodate a broad spectrum of subscapularis pathology, from partial to full and retracted tears; and uses familiar viewing and working portals. This technique creates a single-row, knotless repair. Traction on the superior suture improves visualization and ease of passing more inferior sutures. Risks include unintentional over-tensioning of the repair and medialization of the femoral footprint, which can be avoided with appropriate exposure and arm positioning during repair. Postoperative care includes restriction of external rotation for 3 to 6 weeks and strengthening at 3 months. PMID- 26258043 TI - Single-Portal Arthroscopy of the Central Compartment of the Hip. AB - Since hip arthroscopy has become a standard of orthopaedic practice, the indications have continued to expand as it has proved to be a helpful diagnostic, as well as therapeutic, tool. Access to the hip joint, however, remains challenging for the orthopaedic surgeon who does not routinely perform hip arthroscopy. We present a single-portal arthroscopic technique, showing the feasibility of single-portal arthroscopic access to the hip joint, as well as describing basic indications and instrumentation for single-portal hip arthroscopy. Single-portal hip arthroscopy is ideal for the patient who needs to undergo diagnostic hip arthroscopy or for treatment in patients with simple hip pathology (e.g., removal of loose bodies or debridement). PMID- 26258044 TI - Basket-Weave Technique for Medial Patellofemoral Ligament Reconstruction. AB - The anatomy of the medial patellofemoral ligament (MPFL) has been well defined, with parts of its uppermost fibers having a soft-tissue insertion onto the vastus intermedius. Bone tunnels and implants on the patellar side therefore cannot replicate this anatomic construct precisely. Because of implants and tunnels, complications have been reported with bone tunnel fracture. Similarly, on the femoral side, rigid fixation with implants can result in over-constraint with compromised results. Moreover, bone tunnels cannot be used in skeletally immature cases. To overcome issues related to bone tunneling and implants, as well as to reconstruct the MPFL in a precise anatomic manner, an all-soft-tissue fixation technique was devised. Bony landmarks were used as reference points instead of radiologic markers to achieve a more precise construct and to eliminate intraoperative radiography. Hamstring graft was used to reconstruct the MPFL. Special suturing techniques were used to achieve optimal graft fixation with minimal suture knots. A special tissue elevator-suture passer device was designed to facilitate graft passage and ease in performing the procedure. This technique permits differential tensioning, and therefore one achieves stability throughout the range of motion. PMID- 26258045 TI - Microarray-based optimization to detect genomic deletion mutations. AB - We performed array comparative genome hybridization (aCGH) analyses of five Arabidopsis thaliana mutants with genomic deletions ranging in size from 4 bp to > 5 kb. We used the Roche NimbleGen Arabidopsis CGH 3 * 720 K whole genome custom tiling array to optimize deletion detection. Details of the microarray design and hybridization data have been deposited at the NCBI GEO repository with accession number GSE55327. PMID- 26258046 TI - Platform comparison of detecting copy number variants with microarrays and whole exome sequencing. AB - Copy number variation (CNV) is a common source of genetic variation that has been implicated in many genomic disorders, Mendelian diseases, and common/complex traits. Genomic microarrays are often employed for CNV detection. More recently, whole-exome sequencing (WES) has enabled detection of clinically relevant point mutations and small insertion-deletion exome wide. We evaluated (de Ligt et al. 2013) [1] the utility of short-read WES (SOLiD 5500xl) to detect clinically relevant CNVs in DNA from 10 patients with intellectual disability and compared these results to data from three independent high-resolution microarray platforms. Calls made by the different platforms and detection software are available at dbVar under nstd84. PMID- 26258047 TI - Transcriptional Profiling of Mycobacterium tuberculosis Replicating in the Human Type II Alveolar Epithelial Cell Line, A549. AB - Alveolar epithelial cells outnumber alveolar macrophages by ~500 fold and increasing evidence suggests Mycobacterium tuberculosis may replicate dramatically in these cells during the initial weeks of infecting the lung [1,2]. Here, we report in experimental detail the transcriptional profiling of Mycobacterium tuberculosis replicating at 72 hr post-infection in the human type II alveolar epithelial cell line, A549, as compared to Mycobacterium tuberculosis growing logarithmically in laboratory broth culture [2]. All resulting transcriptional profiling data was deposited to the Gene Expression Omnibus (GEO) database under the accession number GSE58466. PMID- 26258048 TI - The impact of mobility scooters on their users. Does their usage help or hinder?: A state of the art review. AB - As older people start to have difficulty in walking many choose to use a mobility scooter to help them move around. Benefitting from improved design, mobility scooters are becoming an increasingly popular mobility device and are a common sight on many streets. However, very little is known about their usage or their impact in terms of either quality of life or functional health. Whilst mobility scooters may help to improve the quality of life of their users, it is also possible that the sedentary nature of their usage results in a decline of physical functionality and therefore reduced capabilities. Before any substantial research can be carried out it is crucial to understand the importance of a mobility scooter on the lives of the people that use them and to review the initial research published on the effect of scooter use on physical health. This paper is a state-of-the-art review. It describes the current research knowledge on mobility scooters, shows where gaps in knowledge exist and where future research needs to focus. PMID- 26258049 TI - Detection of BRAF mutations from solid tumors using TumorplexTM technology. AB - Allele specific multiplex sequencing (TumorplexTM) is a new molecular platform for the detection of single base mutation in tumor biopsies with high sensitivity for clinical testing. TumorplexTM is a novel modification of Sanger sequencing technology that generates both mutant and wild type nucleotide sequences simultaneously in the same electropherogram. The molecular weight of the two sequencing primers are different such that the two sequences generated are separated, thus eliminating possible suppression of mutant signal by the more abundant wild type signal. TumorplexTM platform technology was tested using BRAF mutation V600E. These studies were performed with cloned BRAF mutations and genomic DNA extracted from tumor cells carrying 50% mutant allele. The lower limit of detection for BRAF V600E was found to be 20 genome equivalents (GE) using genomic DNA extracted from mutation specific cell lines. Sensitivity of the assay was tested by challenging the mutant allele with wild type allele at 20 GE, and was able to detect BRAF mutant signal at a GE ration of 20:1 * 10(7) (mutant to wild-type). This level of sensitivity can detect low abundance of clonal mutations in tumor biopsies and eliminate the need for cell enrichment. *TumorplexTM is a single tube assay that permits the recognition of mutant allele without suppression by wildtype signal.*TumorplexTM provides a high level of sensitivity.*TumorplexTM can be used with small sample size with mixed population of cells carrying heterogeneous gDNA. PMID- 26258050 TI - Trace elements determination in seawater by ICP-MS with on-line pre-concentration on a Chelex-100 column using a 'standard' instrument setup. AB - Trace element determination in seawater is analytically challenging due to the typically very low concentrations of the trace elements and the potential interference of the salt matrix. A common way to address the challenge is to pre concentrate the trace elements on a chelating resin, then rinse the matrix elements from the resin and subsequently elute and detect the trace elements using inductively coupled plasma mass spectrometry (ICP-MS). This technique typically involves time-consuming pre-treatment of the samples for 'off-line' analyses or complicated sample introduction systems involving several pumps and valves for 'on-line' analyses. As an alternative, the following method offers a simple method for 'on-line' analyses of seawater by ICP-MS. As opposed to previous methods, excess seawater was pumped through the nebulizer of the ICP-MS during the pre-concentration step but the gas flow was adjusted so that the seawater was pumped out as waste without being sprayed into the instrument. Advantages of the method include: *Simple and convenient analyses of seawater requiring no changes to the 'standard' sample introduction system except from a resin-filled micro-column connected to the sample tube. The 'standard' sample introduction system refers to that used for routine digest-solution analyses of biota and sediment by ICP-MS using only one peristaltic pump; and*Accurate determination of the elements V, Mn, Co, Ni, Cu, Zn, Cd and Pb in a range of different seawater matrices verified by participation in 6 successive rounds of the international laboratory intercalibration program QUASIMEME. PMID- 26258051 TI - Study of a two species microbial community by an inferential comparative genomic analysis tool: Spatial Analytical Microbial Imaging. AB - Most molecular fingerprinting techniques, including denaturing gradient gel electrophoresis (DGGE) [1], comparative genomic hybridization (CGH) [2], real time polymerase chain reaction (RT-PCR) [3], destroy community structure and/or cellular integrity, therefore lost the info. of the spatial locus and the in situ genomic copy number of the cells. An alternative technique, fluorescence in situ hybridization (FISH) doesn't require sample disintegration but needs to develop specific markers and doesn't provide info. related to genomic copy number. Here, a microbial analysis tool, Spatial Analytical Microbial Imaging (SAMI), is described. An application was performed with a mixture of Synechocystis sp. PCC 6803 and E. coli K-12 MG1655. The intrinsic property of their genome, reflected by the average fluorescence intensity (AFI), distinguished them in 3D. And their growth rates were inferred by comparing the total genomic fluorescence binding area (GFA) with that of the pure culture standards. A 93% of accuracy in differentiating the species was achieved. *SAMI does not require sample disintegration and preserves the community spatial structure.*It measures the 3D locus of cells within the mixture and may differentiate them according to the property of their genome.*It allows assessment of the growth rate of the cells within the mixture by comparing their genomic copy number with that of the pure culture standards. PMID- 26258052 TI - Nanomedicines for dental applications-scope and future perspective. AB - Nanotechnology is directed at manipulating matter at the nanometer level and the application of the same to medicine is called nanomedicine. Over the past few years researchers have developed various nanomedicines for diagnosis, prevention as well as cure of various ailments both locally and systemically. In dentistry, drug loaded nanopharmaceuticals based on nanomaterials have been utilized extensively over the past few years to cure dental problems and facilitate attainment of a near-perfect oral hygiene. Although various drug delivery systems have already been investigated for treating periodontitis, research is currently focused on nanodelivery systems for efficient targeted delivery of drugs to the periodontal pocket. In this context a few nanodelivery systems explored include nanocomposite hydrogels, nanoparticles, nanoemulsion etc. A number of herbal and synthetic drugs examples of which include trichlosan, tetracycline, Harungana madagascariensis leaf extract, minocycline, metronidazole, chlorhexidine have been encapsulated into nanodelivery systems for treating periodontitis. A few examples of polymers investigated as matrices for the delivery of drugs to the periodontal pocket include chitosan, Poly lactic-co-glycolic acid copolymer, poly e caprolactone, polylactic acid, polypropylene, cellulose acetate propionate and ethyl vinyl acetate. In the near future also nanotechnology is expected to find its application in all the specializations of dentistry ranging from diagnosis and treatment of oral cancers to development of colloidal suspension containing millions of active analgesic micron-size dental robots resulting in anesthesia in patients. In the light of the above facts the current editorial focuses on the applications of nanotechnology based nanomedicines which cannot be undermined in the improvement of dental health and hygiene both, in the current as well as in future scenario. PMID- 26258053 TI - Mesoporous silica nanoparticles in target drug delivery system: A review. AB - Due to lack of specification and solubility of drug molecules, patients have to take high doses of the drug to achieve the desired therapeutic effects for the treatment of diseases. To solve these problems, there are various drug carriers present in the pharmaceuticals, which can used to deliver therapeutic agents to the target site in the body. Mesoporous silica materials become known as a promising candidate that can overcome above problems and produce effects in a controllable and sustainable manner. In particular, mesoporous silica nanoparticles (MSNs) are widely used as a delivery reagent because silica possesses favorable chemical properties, thermal stability, and biocompatibility. The unique mesoporous structure of silica facilitates effective loading of drugs and their subsequent controlled release of the target site. The properties of mesoporous, including pore size, high drug loading, and porosity as well as the surface properties, can be altered depending on additives used to prepare MSNs. Active surface enables functionalization to changed surface properties and link therapeutic molecules. They are used as widely in the field of diagnosis, target drug delivery, bio-sensing, cellular uptake, etc., in the bio-medical field. This review aims to present the state of knowledge of silica containing mesoporous nanoparticles and specific application in various biomedical fields. PMID- 26258055 TI - Enhancement of ketorolac tromethamine permeability through rat skin using penetration enhancers: An ex-vivo study. AB - INTRODUCTION: Ketorolac tromethamine (KT), a nonsteroidal anti-inflammatory drug, when given orally causes gastrointestinal disturbances. Its transdermal drug delivery may reduce such side effects associated with them. The present investigation was aimed at evaluating the efficiency of various penetration enhancers for improved permeation of KT through the skin. MATERIALS AND METHODS: A concentration of 1 mg/mL of the drug solution with enhancers was used to evaluate diffusion through the rat skin using a Franz diffusion cell assembly. 20 different penetration enhancers were selected for this study. RESULTS: Saturated fatty acids like stearic and palmitic acid were found to increase the permeation rate of the drug to a great extent whereas unsaturated fatty acid viz. oleic acid exhibited maximum permeation. Increase in permeability efficiency of various penetration enhancers was observed in the following order: Oleic acid > stearic acid > palmitic acid > isopropyl myristate > tween 80 > span 80 > span 40 > span 20 > l-limonene > l-menthol > fenchone > alpha-pinene > urea > dimethyl sulfoxide (DMSO) > triton X-100 > tween 20 > dimethyl formamide > acetone > control > citric acid > ascorbic acid. Ascorbic acid and citric acid had no effect on permeation rate. CONCLUSION: The results revealed that the permeation of KT through the skin can maximally be enhanced using oleic acid-an unsaturated fatty acid. PMID- 26258054 TI - Synthesis and self-assembly of biodegradable polyethylene glycol-poly (lactic acid) diblock copolymers as polymersomes for preparation of sustained release system of doxorubicin. AB - INTRODUCTION: The copolymer of polyethylene glycol (PEG) and polyesters has many interesting properties, such as amphiphilicity, biocompatibility, biodegradability, and self-assembly in an aqueous environment. Diblock copolymers of PEG-polyester can form different structures such as micelles, polymersome, capsules or micro-container in an aqueous environment according to the length of their blocks. MATERIALS AND METHODS: Herein, a series of poly (lactic acid) (PLA) and PEG diblock copolymers were synthesized through the ring-opening polymerization. The polymerization reaction and the copolymer structures were evaluated by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The corresponding copolymers were implemented for the formation of polymersome structures using film rehydration method. Impact of methoxy PEG chain length and hydrophobic weight fraction on particle size of polymersomes were studied, and the proper ones were selected for loading of doxorubicin (DOX) via pH gradient method. RESULTS AND DISCUSSION: Results obtained from (1)HNMR and GPC revealed that microwave irradiation is a simple and reliable method for the synthesis of PEG-PLA copolymers. Further analysis indicated the copolymer with relative molecular weight of PLA to PEG ratios of 3 or f Eo ~ 25% produced the smallest size polymersomes. Polymersomes prepared from PEG5000 to PLA15000 were more capable in loading and sustained release of DOX than those prepared from PEG2000 to PLA6000. CONCLUSION: In conclusion copolymers of PEG/PLA with f OE ~25% and relatively higher molecular weight are more suitable for encapsulation and providing sustained release of DOX. PMID- 26258056 TI - Fabrication and optimization of camptothecin loaded Eudragit S 100 nanoparticles by Taguchi L4 orthogonal array design. AB - INTRODUCTION: The objective of this investigation was to design and optimize the experimental conditions for the fabrication of camptothecin (CPT) loaded Eudragit S 100. Nanoparticles, and to understand the effect of various process parameters on the average particles size, particle size uniformity and surface area of the prepared polymeric nanoparticles using Taguchi design. MATERIALS AND METHODS: CPT loaded Eudragit S 100 nanoparticles were prepared by nanoprecipitation method and characterized by particles size analyzer. Taguchi orthogonal array design was implemented to study the influence of seven independent variables on three dependent variables. Eight experimental trials involving seven independent variables at higher and lower levels were generated by design expert. RESULTS: Factorial design result has shown that (a) except, beta-cyclodextrin concentration all other parameters do not significantly influenced the average particle size (R1); (b) except, sonication duration and aqueous phase volume, all other process parameters significantly influence the particle size uniformity; (c) all the process parameters does not significantly influence the surface area. CONCLUSION: The R1, particle size uniformity and surface area of the prepared drug-loaded polymeric nanoparticles were found to be 120 nm, 0.237 and 55.7 m(2) /g and the results were good correlated with the data generated by the Taguchi design method. PMID- 26258057 TI - Dual agents loaded polymeric nanoparticle: Effect of process variables. AB - AIM AND OBJECTIVES: In the present investigation dual agents i.e., hesperidin and diazepam loaded polymeric nanoparticles (NPs) were formulated by nanoprecipitation method and optimized using three-level factorial design. METHODS: The developed NPs were optimized keeping poly (lactic-co-glycolic) acid (PLGA), poloxamer amount as independent process variable and z-average, percentage drug entrapment as a dependent response. The optimized NP was subjected to in vitro drug release study to investigate drug release mechanism from NP. Cell viability assay was performed on Vero cell line to confirm the safety of NP. RESULTS: Drug loaded NP showed z-average in the range of 189-307 d.nm with percentage drug entrapment for diazepam and hesperidin 62-89% and 68 92%, respectively. In vitro drug release studies showed controlled drug release behavior was observed from polymeric NP across dialysis membrane compared to aqueous drug solution. Cell viability assay showed drug dependent cytotoxicity on Vero cell line, however, polymeric NP showed less cytotoxicity compared with aqueous drug solution. PMID- 26258058 TI - Microspheres and tablet in capsule system: A novel chronotherapeutic system of ketorolac tromethamine for site and time specific delivery. AB - The objective of the present work was to develop a novel delivery system of ketorolac tromethamine (KT) for dual pulse release based on microspheres and tablet in capsule system (MATICS) as a treatment modality for rheumatoid arthritis. The design consisted of an impermeable hard gelatin capsule body, in which a core tablet was (second pulse) placed in the bottom and sealed with a hydrogel plug (HP2). The body was locked with enteric coated cap filled with KT microspheres (first pulse). The microspheres for first pulse were selected by screening the formulations (M1-M6), and M1 with least particle size of 96.38 +/- 0.05 MUm, highest drug loading of 25.10% +/- 0.28% and maximum CDR of 89.32% +/- 0.21% was adjudged as the best formulation. The HP2 tablet was selected based on its capability for maintaining a lag period of 6 h. The selection criterion of the second pulse (core tablet: T3) was its disintegration time of 4.02 +/- 0.53 min and CDR of 99.10% +/- 0.32% in 30 min. All the optimized formulations were assembled in accordance with the proposed design to form pulsatile MATICS and evaluated for in vitro release. MATICS displayed delayed sustained CDR of 80.15% in 8 h from the first pulse (microspheres) after a lag time of 2 h, followed by 97.05% KT release from second pulse (core tablet) in simulated colonic fluid within 10 h. Conclusively, in vitro pulsatile release was a rational combination of delayed sustained and immediate release of KT that has the potential to combat the pain at night and morning stiffness. Incorporation of two pulses in one system offers a reduction in dose frequency and better pain management. PMID- 26258059 TI - Preparation and characterization of cefuroxime axetil solid dispersions using hydrophilic carriers. AB - AIM: The objective of the current study is to increase the dissolution rate of cefuroxime axetil (CA) by formation of binary CA solid dispersion using water soluble carriers such as polyvinylpyrrolidone (PVP K30) and polyethylene glycol (PEG 4000). METHODS: Solid dispersions (SDs) between CA and PVP K30/PEG 4000 were formed by dissolving both compounds in a common solvent, methanol, which were rotary evaporated at 40 degrees C for 12 h. Physical mixtures between CA and PVP K30/PEG 4000 were also formulated as to compare the efficiency of SDs. The physicochemical properties of CA and all its formulations were then characterized using differential scanning calorimetric analysis (DSC), powder X-ray diffraction studies (PXRD), and Fourier transform infrared spectroscopy (FTIR). RESULTS: All SD formulations were found to have a higher dissolution rate comparatively to pure CA, while only physical mixtures of PVP K30 were found having a significantly higher dissolution rate. The enhancement of dissolution rate SD by PVP K30 may be caused by increase wettability, solubility, reduction in particle size or the formation of CA beta crystalline. Increment of dissolution rate of CA SDs by PEG 4000 similarly may be caused by increase wettability, solubility, and reduction in particle size. This phenomenon may also be caused by amorphization as suggested by DSC and PXRD. CONCLUSIONS: The SD of CA with PVP K30 and PEG 4000, lends an ample credence for better therapeutic efficacy. PMID- 26258060 TI - Reader's Forum. PMID- 26258061 TI - Cone-beam computed tomography based evaluation of rotational patterns of dentofacial structures in skeletal Class III deformity with mandibular asymmetry. AB - OBJECTIVE: The purpose of this study was to assess rotational patterns of dentofacial structures according to different vertical skeletal patterns by cone beam computed tomography (CBCT) and analyze their influence on menton deviation in skeletal Class III deformity with mandibular asymmetry. METHODS: The control group consisted of 30 young adults (15 men, 15 women) without any severe skeletal deformity. The asymmetry group included 55 adults (28 men, 27 women) with skeletal Class III deformity and at least 3-mm menton deviation from the midsagittal plane; it was divided into the hyperdivergent and hypodivergent subgroups using a mandibular plane angle cutoff of 35 degrees . Fourteen rotational variables of the dental arches and mandible were measured and compared among the groups. Correlations between menton deviation and the other variables were evaluated. RESULTS: The asymmetry group showed significantly larger measurements of roll and yaw in the mandible than the control group. The hypodivergent subgroup showed significant differences in maxillary posterior measurements of yaw (p < 0.01) and maxillary anterior shift (p < 0.05) compared with the hyperdivergent subgroup. All the mandibular measurements had significant correlations with menton deviation (p < 0.01). Most measurements of roll were positively correlated with one another (p < 0.01). Measurements of yaw and roll in the posterior regions were also positively correlated (p < 0.05). CONCLUSIONS: Menton deviation in skeletal Class III deformity with mandibular asymmetry is influenced by rotation of mandibular posterior dentofacial structures. The rotational patterns vary slightly according to the vertical skeletal pattern. PMID- 26258062 TI - Comparison of shear bond strength of orthodontic brackets using various zirconia primers. AB - OBJECTIVE: The aim of this study was to compare the shear bond strength (SBS) of orthodontic brackets bonded to zirconia surfaces using three different zirconia primers and one silane primer, and subjected to thermocycling. METHODS: We designed 10 experimental groups following the surface treatment and thermocycling. The surface was treated with one of the following method: no primer (NP), Porcelain Conditioner (PC), Z-PRIME Plus (ZP), Monobond Plus (MP) and Zirconia Liner Premium (ZL) (n=20). Then each group was subdivided to non thermocycled and thermocycled groups (NPT, PC, ZPT, MPT, ZLT) (n=10). Orthodontic brackets were bonded to the specimens using TransbondTM XT Paste and light cured for 15 s at 1,100 mW/cm(2). The SBS was measured at a 1 mm/min crosshead speed. The failure mode was assessed by examination with a stereomicroscope and the amount of bonding resin remaining on the zirconia surface was scored using the modified adhesive remnant index (ARI). RESULTS: The SBS of all experimental groups decreased after thermocycling. Before thermocycling, the SBS was ZL, ZP >= MP >= PC > NP but after thermocycling, the SBS was ZLT >= MPT >= ZPT > PCT = NPT (p > 0.05). For the ARI score, both of the groups lacking primer (NP and NPT) displayed adhesive failure modes, but the groups with zirconia primers (ZP, ZPT, MP, MPT, ZL, and ZLT) were associated with mixed failure modes. CONCLUSIONS: Surface treatment with a zirconia primer increases the SBS relative to no-primer or silane primer application between orthodontic brackets and zirconia prostheses. PMID- 26258063 TI - Comparative evaluation of molar distalization therapy using pendulum and distal screw appliances. AB - OBJECTIVE: To compare dentoalveolar and skeletal changes produced by the pendulum appliance (PA) and the distal screw appliance (DS) in Class II patients. METHODS: Forty-three patients (19 men, 24 women) with Class II malocclusion were retrospectively selected for the study. Twenty-four patients (mean age, 12.2 +/- 1.5 years) were treated with the PA, and 19 patients (mean age, 11.3 +/- 1.9 years) were treated with the DS. The mean distalization time was 7 months for the PA group and 9 months for the DS group. Lateral cephalograms were obtained at T1, before treatment, and at T2, the end of distalization. A Mann-Whitney U test was used for statistical comparisons of the two groups between T1 and T2. RESULTS: PA and DS were equally effective in distalizing maxillary molars (4.7 mm and 4.2 mm, respectively) between T1 and T2; however, the maxillary first molars showed less distal tipping in the DS group than in the PA group (3.2 degrees vs. 9.0 degrees , respectively). Moreover, significant premolar anchorage loss (2.7 mm) and incisor proclination (5.0 degrees ) were noted in the PA group, whereas premolar distal movement (1.9 mm) and no significant changes at the incisor (0.1 degrees ) were observed in the DS group. No significant sagittal or vertical skeletal changes were detected between the two groups during the distalization phase. CONCLUSIONS: PA and DS seem to be equally effective in distalizing maxillary molars; however, greater distal molar tipping and premolar anchorage loss can be expected using PA. PMID- 26258064 TI - Differences in the mandibular premolar positions in Angle Class I subjects with different vertical facial types: A cone-beam computed tomography study. AB - OBJECTIVE: To compare the positions of the mandibular premolars in Angle Class I subjects according to vertical facial type. The results will provide a theoretical basis for predicting effective tooth movement in orthodontic treatment. METHODS: Cephalometric parameters were determined using cone-beam computed tomography in 120 Angle Class I subjects. Subjects were categorized as short, normal, and long face types according to the Frankfort mandibular angle. Parameters indicating the position of the mandibular right premolars and the mandible were also measured. RESULTS: The angle between the mandibular first premolar axis and buccal cortex, the distance between the root apex and buccal cortex, angle of vestibularization, arc of vestibularization, and root apex maximum movable distance were significantly greater in the short face type than in the long and norm face types. The angle between the mandibular second premolar axis and buccal cortex, the distance from root apex to buccal cortex, and the arc of vestibularization were significantly greater in the short face type than in the normal face type. CONCLUSIONS: There are significant differences in the mandibular premolar positions in Class I subjects according to vertical facial type. PMID- 26258065 TI - Dentoskeletal features in individuals with ectopic eruption of the permanent maxillary first molar. AB - OBJECTIVE: The aim of the study was to analyze the prevalence and distribution of ectopic eruption of the permanent maxillary first molar (EEM) in individuals scheduled for orthodontic treatment and to investigate the association of EEM with dental characteristics, maxillary skeletal features, crowding, and other dental anomalies. METHODS: A total of 1,317 individuals were included and randomly divided into two groups. The first 265 subjects were included as controls, while the remaining 1,052 subjects included the sample from which the final experimental EEM group was derived. The mesiodistal (M-D) crown width of the deciduous maxillary second molar and permanent maxillary first molar, maxillary arch length (A-PML), maxillomandibular transverse skeletal relationships (anterior and posterior transverse interarch discrepancies, ATID and PTID), maxillary and mandibular tooth crowding, and the presence of dental anomalies were recorded for each subject, and the statistical significance of differences in these parameters between the EEM and control groups was determined using independent sample t-tests. Chi-square tests were used to compare the prevalence of other dental anomalies between the two groups. RESULTS: The prevalence of maxillary EEM was 2.5%. The M-D crown widths, ATID and PTID, and tooth crowding were significantly greater, while A-PML was significantly smaller, in the EEM group than in the control group. Only two subjects showed an association between EEM and maxillary lateral incisor anomalies, which included agenesis in one and microdontia in the other. CONCLUSIONS: EEM may be a risk factor for maxillary arch constriction and severe tooth crowding. PMID- 26258066 TI - Effect of activation and preactivation on the mechanical behavior and neutral position of stainless steel and beta-titanium T-loops. AB - OBJECTIVE: To quantify, for each activation, the effect of preactivations of differing distribution and intensity on the neutral position of T-loops (7-mm height), specifically the horizontal force, moment to force (M/F) ratio, and load to deflection ratio. METHODS: A total 100 loops measuring 0.017 * 0.025 inches in cross-section were divided into two groups (n = 50 each) according to composition, either stainless steel or beta-titanium. The two groups were further divided into five subgroups, 10 loops each, corresponding to the five preactivations tested: preactivations with occlusal distribution (0 degrees , 20 degrees , and 40 degrees ), gingival distribution (20 degrees ), and occlusal gingival distribution (40 degrees ). The loops were subjected to a total activation of 6-mm with 0.5-mm iterations. Statistical analysis was performed using comprised ANOVA and Bonferoni multiple comparison tests, with a significance level of 5%. RESULTS: The location and intensity of preactivation influenced the force intensity. For the M/F ratio, the highest value achieved without preactivation was lower than the height of the loop. Without preactivation, the M/F ratio increased with activation, while the opposite effect was observed with preactivation. The increase in the M/F ratio was greater when the preactivation distribution was partially or fully gingival. CONCLUSIONS: Depending on the preactivation distribution, displacement of uprights is higher or lower than the activation, which is a factor to consider in clinical practice. PMID- 26258067 TI - New approach of maxillary protraction using modified C-palatal plates in Class III patients. AB - Maxillary protraction is the conventional treatment for growing Class III patients with maxillary deficiency, but it has undesirable dental effects. The purpose of this report is to introduce an alternative modality of maxillary protraction in patients with dentoskeletal Class III malocclusion using a modified C-palatal plate connected with elastics to a face mask. This method improved skeletal measurements, corrected overjet, and slightly improved the profile. The patients may require definitive treatment in adolescence or adulthood. The modified C-palatal plate enables nonsurgical maxillary advancement with maximal skeletal effects and minimal dental side effects. PMID- 26258069 TI - Targeting Aggressive Cancer Stem Cells in Glioblastoma. AB - Glioblastoma (GBM) is the most common and fatal type of primary brain tumor. Gliosarcoma (GSM) is a rarer and more aggressive variant of GBM that has recently been considered a potentially different disease. Current clinical treatment for both GBM and GSM includes maximal surgical resection followed by post-operative radiotherapy and concomitant and adjuvant chemotherapy. Despite recent advances in treating other solid tumors, treatment for GBM and GSM still remains palliative, with a very poor prognosis and a median survival rate of 12-15 months. Treatment failure is a result of a number of causes, including resistance to radiotherapy and chemotherapy. Recent research has applied the cancer stem cells theory of carcinogenesis to these tumors, suggesting the existence of a small subpopulation of glioma stem-like cells (GSCs) within these tumors. GSCs are thought to contribute to tumor progression, treatment resistance, and tumor recapitulation post-treatment and have become the focus of novel therapy strategies. Their isolation and investigation suggest that GSCs share critical signaling pathways with normal embryonic and somatic stem cells, but with distinct alterations. Research must focus on identifying these variations as they may present novel therapeutic targets. Targeting pluripotency transcription factors, SOX2, OCT4, and Nanog homeobox, demonstrates promising therapeutic potential that if applied in isolation or together with current treatments may improve overall survival, reduce tumor relapse, and achieve a cure for these patients. PMID- 26258068 TI - Implications of the Hybrid Epithelial/Mesenchymal Phenotype in Metastasis. AB - Transitions between epithelial and mesenchymal phenotypes - the epithelial to mesenchymal transition (EMT) and its reverse the mesenchymal to epithelial transition (MET) - are hallmarks of cancer metastasis. While transitioning between the epithelial and mesenchymal phenotypes, cells can also attain a hybrid epithelial/mesenchymal (E/M) (i.e., partial or intermediate EMT) phenotype. Cells in this phenotype have mixed epithelial (e.g., adhesion) and mesenchymal (e.g., migration) properties, thereby allowing them to move collectively as clusters. If these clusters reach the bloodstream intact, they can give rise to clusters of circulating tumor cells (CTCs), as have often been seen experimentally. Here, we review the operating principles of the core regulatory network for EMT/MET that acts as a "three-way" switch giving rise to three distinct phenotypes - E, M and hybrid E/M - and present a theoretical framework that can elucidate the role of many other players in regulating epithelial plasticity. Furthermore, we highlight recent studies on partial EMT and its association with drug resistance and tumor initiating potential; and discuss how cell-cell communication between cells in a partial EMT phenotype can enable the formation of clusters of CTCs. These clusters can be more apoptosis-resistant and have more tumor-initiating potential than singly moving CTCs with a wholly mesenchymal (complete EMT) phenotype. Also, more such clusters can be formed under inflammatory conditions that are often generated by various therapies. Finally, we discuss the multiple advantages that the partial EMT or hybrid E/M phenotype have as compared to a complete EMT phenotype and argue that these collectively migrating cells are the primary "bad actors" of metastasis. PMID- 26258070 TI - EWS/FLI1 Target Genes and Therapeutic Opportunities in Ewing Sarcoma. AB - Ewing sarcoma is an aggressive bone malignancy that affect children and young adults. Ewing sarcoma is the second most common primary bone malignancy in pediatric patients. Although significant progress has been made in the treatment of Ewing sarcoma since it was first described in the 1920s, in the last decade survival rates have remained unacceptably invariable, thus pointing to the need for new approaches centered in the molecular basis of the disease. Ewing sarcoma driving mutation, EWS-FLI1, which results from a chromosomal translocation, encodes an aberrant transcription factor. Since its first characterization in 1990s, many molecular targets have been described to be regulated by this chimeric transcription factor. Their contribution to orchestrate Ewing sarcoma phenotype has been reported over the last decades. In this work, we will focus on the description of a selection of EWS/FLI1 targets, their functional role, and their potential clinical relevance. We will also discuss their role in other types of cancer as well as the need for further studies to be performed in order to achieve a broader understanding of their particular contribution to Ewing sarcoma development. PMID- 26258071 TI - HABP2 is a Novel Regulator of Hyaluronan-Mediated Human Lung Cancer Progression. AB - BACKGROUND: Lung cancer is a devastating disease with limited treatment options. Many lung cancers have changes in their microenvironment including upregulation of the extracellular matrix glycosaminoglycan, hyaluronan (HA), which we have previously demonstrated can regulate the activity of the extracellular serine protease, hyaluronan binding protein 2 (HABP2). This study examined the functional role of HABP2 on HA-mediated human lung cancer dynamics. METHODS: Immunohistochemical analysis was performed on lung cancer patient samples using anti-HABP2 antibody. Stable control, shRNA, and HABP2 overexpressing human lung adenocarcinoma cells were evaluated using immunoblot analysis, migration, extravasation, and urokinase plasminogen activator (uPA) activation assays with or without high-molecular weight HA or low-molecular weight HA (LMW-HA). In human lung cancer xenograft models, primary tumor growth rates and lung metastasis were analyzed using consecutive tumor volume measurements and nestin immunoreactivity in nude mouse lungs. RESULTS: We provide evidence that HABP2 is an important regulator of lung cancer progression. HABP2 expression was increased in several subtypes of patient non-small cell lung cancer samples. Further, HABP2 overexpression increased LMW-HA-induced uPA activation, migration, and extravasation in human lung adenocarcinoma cells. In vivo, overexpression of HABP2 in human lung adenocarcinoma cells increased primary tumor growth rates in nude mice by ~2-fold and lung metastasis by ~10-fold compared to vector control cells (n = 5/condition). CONCLUSION: Our data suggest a possible direct effect of HABP2 on uPA activation and lung cancer progression. Our observations suggest that exploration of HABP2 in non-small cell lung carcinoma merits further study both as a diagnostic and therapeutic option. PMID- 26258073 TI - Intracardiac Metastasis From Non-Small Cell Lung Cancer. AB - A 56-year-old female with history of stage IIA adenosquamous lung carcinoma treated 13 months prior to presentation with lobectomy, mediastinal lymph node dissection, and adjuvant chemotherapy, presented for several weeks of worsening dyspnea. Exam was non-focal aside from tachycardia. Computed tomography of the chest revealed a large 4 cm * 5 cm mass in the bilateral ventricular myocardium. There was also evidence of metastatic disease elsewhere in the body, including a supraclavicular lymph node that was positive for metastatic adenosquamous lung carcinoma. She started whole heart radiotherapy and was to commence chemotherapy but passed away. This report discusses important aspects of diagnosis of this not uncommon condition that many oncologists may come across. We also discuss differential diagnosis of an isolated intracardiac mass as first-diagnosis presentations, and discuss the great importance of multidisciplinary cardio oncologic management and clinical prioritization. PMID- 26258074 TI - Sustained Complete Response to Cytotoxic Therapy and the PARP Inhibitor Veliparib in Metastatic Castration-Resistant Prostate Cancer - A Case Report. AB - Solid tumors harboring BRCA1 or BRCA2 mutations have been shown to respond to PARP inhibitors. These responses are partial and transient. In this case report, we describe an 82-year-old male with poorly differentiated prostate cancer with metastases to the lung, liver, abdomen, and bowel. Molecular testing demonstrated alterations in BRCA2, ERG, and TP53. Based on this result, he was enrolled in a therapeutic trial and received carboplatin, gemcitabine, and veliparib, to which he had a partial response. He continued to respond while on veliparib maintenance alone, and after 38 cycles he had a sustained complete response. A sustained complete response to PARP inhibitor-based therapy has not previously been described for prostate cancer. This case suggests that cytotoxic therapy in combination with PARP inhibitors may yield exceptional responses, and molecular studies may help guide patient selection for these therapies. PMID- 26258075 TI - Pre-Clinical Models of Diffuse Intrinsic Pontine Glioma. AB - Diffuse intrinsic pontine glioma (DIPG) is a rare and incurable brain tumor that arises in the brainstem of children predominantly between the ages of 6 and 8. Its intricate morphology and involvement of normal pons tissue precludes surgical resection, and the standard of care today remains fractionated radiation alone. In the past 30 years, there have been no significant advances made in the treatment of DIPG. This is largely because we lack good models of DIPG and therefore have little biological basis for treatment. In recent years, however, due to increased biopsy and acquisition of autopsy specimens, research is beginning to unravel the genetic and epigenetic drivers of DIPG. Insight gleaned from these studies has led to improvements in approaches to both model these tumors in the lab and to potentially treat them in the clinic. This review will detail the initial strides toward modeling DIPG in animals, which included allograft and xenograft rodent models using non-DIPG glioma cells. Important advances in the field came with the development of in vitro cell and in vivo xenograft models derived directly from autopsy material of DIPG patients or from human embryonic stem cells. Finally, we will summarize the progress made in the development of genetically engineered mouse models of DIPG. Cooperation of studies incorporating all of these modeling systems to both investigate the unique mechanisms of gliomagenesis in the brainstem and to test potential novel therapeutic agents in a preclinical setting will result in improvement in treatments for DIPG patients. PMID- 26258072 TI - Overview of Methods for Overcoming Hindrance to Drug Delivery to Tumors, with Special Attention to Tumor Interstitial Fluid. AB - Every drug used to treat cancer (chemotherapeutics, immunological, monoclonal antibodies, nanoparticles, radionuclides) must reach the targeted cells through the tumor environment at adequate concentrations, in order to exert their cell killing effects. For any of these agents to reach the goal cells, they must overcome a number of impediments created by the tumor microenvironment (TME), beginning with tumor interstitial fluid pressure (TIFP), and a multifactorial increase in composition of the extracellular matrix (ECM). A primary modifier of TME is hypoxia, which increases the production of growth factors, such as vascular endothelial growth factor and platelet-derived growth factor. These growth factors released by both tumor cells and bone marrow recruited myeloid cells form abnormal vasculature characterized by vessels that are tortuous and more permeable. Increased leakiness combined with increased inflammatory byproducts accumulates fluid within the tumor mass (tumor interstitial fluid), ultimately creating an increased pressure (TIFP). Fibroblasts are also up regulated by the TME, and deposit fibers that further augment the density of the ECM, thus, further worsening the TIFP. Increased TIFP with the ECM are the major obstacles to adequate drug delivery. By decreasing TIFP and ECM density, we can expect an associated rise in drug concentration within the tumor itself. In this overview, we will describe all the methods (drugs, nutraceuticals, and physical methods of treatment) able to lower TIFP and to modify ECM used for increasing drug concentration within the tumor tissue. PMID- 26258076 TI - The Reliability of the Canadian Triage and Acuity Scale: Meta-analysis. AB - BACKGROUND: Although the Canadian Triage and Acuity Scale (CTAS) have been developed since two decades ago, the reliability of the CTAS has not been questioned comparing to moderating variable. AIMS: The study was to provide a meta-analytic review of the reliability of the CTAS in order to reveal to what extent the CTAS is reliable. MATERIALS AND METHODS: Electronic databases were searched to March 2014. Only studies were included that had reported samples size, reliability coefficients, adequate description of the CTAS reliability assessment. The guidelines for reporting reliability and agreement studies (GRRAS) were used. Two reviewers independently examined abstracts and extracted data. The effect size was obtained by the z-transformation of reliability coefficients. Data were pooled with random-effects models and meta-regression was done based on method of moments estimator. RESULTS: Fourteen studies were included. Pooled coefficient for the CTAS was substantial 0.672 (CI 95%: 0.599 0.735). Mistriage is less than 50%. Agreement upon the adult version, among nurse physician and near countries is higher than pediatrics version, other raters and farther countries, respectively. CONCLUSION: The CTAS showed acceptable level of overall reliability in the emergency department but need more development to reach almost perfect agreement. PMID- 26258077 TI - YouTube as a Source of Information on Ebola Virus Disease. AB - BACKGROUND: The current West Africa epidemic of Ebola virus disease (EVD), which began from Guinea in December 2013, has been the longest and deadliest Ebola outbreak to date. With the propagation of the internet, public health officials must now compete with other official and unofficial sources of information to get their message out. AIMS: This study aimed at critically appraising videos available on one popular internet video site (YouTube) as a source of information for Ebola virus disease (EVD). MATERIALS AND METHODS: Videos were searched in YouTube (http://www.youtube.com) using the keyword "Ebola outbreak" from inception to November 1, 2014 with the default "relevance" filter. Only videos in English language under 10 min duration within first 10 pages of search were included. Duplicates were removed and the rest were classified as useful or misleading by two independent reviewers. Video sources were categorized by source. Inter-observer agreement was evaluated with kappa coefficient. Continuous and categorical variables were analyzed using the Student t-test and Chi-squared test, respectively. RESULTS: One hundred and eighteen out of 198 videos were evaluated. Thirty-one (26.27%) videos were classified as misleading and 87 (73.73%) videos were classified as useful. The kappa coefficient of agreement regarding the usefulness of the videos was 0.68 (P < 0.001). Independent users were more likely to post misleading videos (93.55% vs 29.89%, OR = 34.02, 95% CI = 7.55-153.12, P < 0.001) whereas news agencies were most likely to post useful videos (65.52% vs 3.23%, OR = 57.00, 95% CI = 7.40-438.74, P < 0.001). CONCLUSIONS: This study demonstrates that majority of the internet videos about Ebola on YouTube were characterized as useful. Although YouTube seems to generally be a useful source of information on the current outbreak, increased efforts to disseminate scientifically correct information is desired to prevent unnecessary panic among the among the general population. PMID- 26258078 TI - Anti-Inflammatory Dietary Combo in Overweight and Obese Women with Polycystic Ovary Syndrome. AB - BACKGROUND: Polycystic ovary syndrome (PCOS) is of clinical and public health importance, affecting up to one in five women of reproductive age. It has significant and diverse clinical implications including reproductive, metabolic, and psychological features. AIM: The study was to investigate the effect of anti inflammatory dietary combo on metabolic, endocrine, inflammatory, and reproductive profiles in overweight and obese women with PCOS. MATERIALS AND METHODS: A total of 100 nonpregnant, overweight, and obese adult females with PCOS according to the Rotterdam criteria, were screened during the year 2012, and 75 completed the trial. At baseline and study end, fasting blood samples were drawn to measure biological markers, body fat percent (BFP), and visceral fat area (VFA) were assessed by the InBody720 device and anthropometric measurements were done for all participants who were subjected to an anti-inflammatory hypocaloric diet and physical activity for 12 weeks. RESULTS: At study completion, we achieved moderate weight loss of (+/- 7%) and significant improvements in body composition, hormones and menstrual cyclicity, blood pressure, glucose homeostasis, dyslipidemia, C-reactive protein (CRP), and serum amyloid A (SAA) (surrogate measures of cardiovascular risk (CVR)). This was a clinically relevant weight loss that is associated with a reduced prevalence of type 2 diabetes mellitus (DM2) and metabolic syndrome (MS) in the general population and improved fertility outcomes in PCOS. We achieved 63% regain of menstrual cyclicity and 12% spontaneous pregnancy rate within 12 week. CONCLUSIONS: We have explored an additional dietary treatment option with good prognostic metabolic and reproductive responses to weight loss that occur in overweight and obese PCOS. PMID- 26258079 TI - Fish Oil Intake and Seizure Control in Children with Medically Resistant Epilepsy. AB - BACKGROUND: There is considerable evidence which suggests that Omega 3 polyunsaturated fatty acids may have a potential use in the treatment of epilepsy. AIM: The study was to investigate the effect of Omega 3 polyunsaturated fatty acids (as fish oil supplementation) in reducing the frequency and severity of epileptic seizures in children with medically resistant epilepsy. MATERIALS AND METHODS: In the case-control study, a total of 70 children with medically resistant epilepsy underwent assessment of the frequency and severity of the epileptic attacks at baseline, after one month, two months and three months from the beginning of the study; 35 children received fish oil and the other 35 children received placebo. RESULTS: The number of children who received fish oil, having 0 epileptic attacks increased from 0%, before starting the study, up to 57.1% at the end of the third month, while the improvement was minimal in the placebo group, with a significant difference in the improvement between the intervention and the control groups. There was no statistically significant difference in improvement in the severity of the seizures either between cases and control or between the beginning and the end of the study. CONCLUSION: Omega 3 polyunsaturated fatty acids elevated the seizure threshold in epileptic patients and may help in achieving seizure control. PMID- 26258080 TI - Evaluation of the Relationship Between Musculoskeletal Discomforts and Occupational Stressors Among Nurses. AB - BACKGROUND: Stress in nurses may increase the prevalence of musculoskeletal discomforts. AIM: The aim of this study was to determine the prevalence of musculoskeletal discomforts and job stress among nurses and to investigate the association between musculoskeletal discomforts and occupational stressors. MATERIALS AND METHODS: In this cross-sectional study, 144 nurses in one of the main referral hospitals of Tehran-Iran were randomly selected and studied. Data were collected by HSE job stress questionnaire and The Cornell Musculoskeletal Discomfort Questionnaire through interviews with nurses in their workplace. RESULTS: Most reported musculoskeletal discomforts localized in the neck, back, knee and shoulder and the minimal discomforts were in wrist and elbow. On the other hand, stressors such as demand, changes in workplace, control and responsibilities had significant effect on increasing musculoskeletal discomforts of organs such as neck, shoulders and back (P < 0.001). CONCLUSION: There was a significant association between stressors such as demand, control, responsibilities and changes in workplace and reported musculoskeletal disorders, especially in neck, shoulders and back. It is suggested to use defined programs for management and control of stressors to control occupational stress in nurses. Moreover, prevention of musculoskeletal discomforts due to their high prevalence in the study population is important. PMID- 26258081 TI - Lithium-Induced Minimal Change Disease and Acute Kidney Injury. AB - CONTEXT: Lithium carbonate is a psychiatric medication commonly used in the treatment of bipolar disorder. It has been implicated in inducing nephrogenic diabetes inspidus, chronic tubulointerstitial nephropathy, and acute tubular necrosis. We describe a case of lithium-induced minimal change disease (MCD) and acute kidney injury (AKI). CASE REPORT: A 32-year-old female with a medical history of bipolar disorder treated with chronic lithium therapy presented with anasarca, fatigue, and tremors. Work-up revealed supra-therapeutic lithium levels, hypoalbuminemia, and significant proteinuria. The patient was treated conservatively with fluids and discontinuation of lithium therapy. Subsequently, she developed significant AKI and persistent proteinuria. She underwent a renal biopsy that demonstrated effacement of podocyte foot processes consistent with lithium-induced MCD. This was treated with corticosteroids, which decreased the proteinuria and resolved all the patient's symptoms. CONCLUSION: Lithium-induced MCD is a rare disease that affects patients of all ages. It is often associated with therapeutic lithium and is typically resolved with discontinuation of lithium. In some cases, concurrent AKI may result due to vascular obstruction from hyperalbuminuria and associated renal interstitial edema. Corticosteroids may be needed to reduce the proteinuria and prevent progression to chronic kidney disease. As such, patients on lithium therapy may benefit from monitoring of glomerular function via urinalysis to prevent the onset of nephrotic syndrome. PMID- 26258082 TI - Emphysematous Cystitis: A Rare Disease of Genito-Urinary System. AB - CONTEXT: Emphysematous cystitis (EC) is a rare infection of the urinary tract that results in gas production in the bladder. It is more common in diabetic and female patients, and can be associated with more serious complications, including pyelonephritis. CASE REPORT: We describe a case of recurrent bacterial cystitis caused by Escherichia coli (E. coli). An incidental finding in our patient of pneumaturia on computed tomography (CT) scan prompted further work-up. Differential diagnoses for pneumaturia include infection, trauma, and fistula, most commonly colovesicular. The patient history ruled out trauma and CT scanning ruled out a fistula; culture of the urine then showed a bacterial load greater than 100,000 E. coli/mL. The patient was then diagnosed with EC. She was treated with ceftriaxone and released in stable condition. CONCLUSION: The literature was scarce when it came to diagnoses of EC based on bacterial load. We present this case to increase health care providers' awareness of recurrent EC with a urine culture bacterial load greater than 100,000 E. coli/mL. PMID- 26258083 TI - A Rare Combination of Giant Right Coronary Artery Aneurysm. AB - CONTEXT: Giant coronary artery aneurysm (CAA) in adults is a rare clinical entity with an estimated incidence of 0.02%. CAA is commonly found in the right coronary artery with significant number of cases associated with fistula formation. CASE REPORT: We describe a rare case of an 87 year-old man with large CAA with fistulous drainage into the right ventricle (RV) along with RV free wall vegetation as a cause of chronic weakness and lethargy. CONCLUSION: Giant CAA with fistulous drainage to the RV could present in the form of infective endocarditis. Early detection and surgical treatment would provide a significant benefit to these patients. PMID- 26258084 TI - Statin Intolerance and Vitamin D Supplementation: Sunny, but a Few Clouds Remain.... PMID- 26258085 TI - Statin Intolerance and Vitamin D Supplementation. PMID- 26258086 TI - The Social Determinants of Health (SDH) in Iran: A Systematic Review Article. AB - BACKGROUND: Many studies have been conducted in Iran in order to investigate the status of social determinants of health (SDH) and their associations with health indicators. This study aimed to review the Iranian studies conducted on SDH. METHODS: A systematic review of all Iranian Persian and English languages articles published between 2005 and 2014 on the SDH was conducted using the search of SID, Iran Medex, Iran Doc, Medline, Embase, Scopus, and Google Scholar databases. The eligibility criteria were studies describing SDH status, designed based on the WHO conceptual framework of SDH, published in Persian or English languages, and full text articles. The structured narrative approach was used to synthesize the data. RESULTS: The entire review process led to the selection of 21 papers. Most of studies had been conducted on the intermediary (38%) and structural (33%) components and determinants in Iran, 4 studies (19%) on the study of all components affecting the health and health inequality and, finally, the minimum number of studies (10%) on the context components and determinants. The focus of 43% of selected studies was on the WHO conceptual framework of SDH and had evaluated this model as an appropriate conceptual framework. CONCLUSION: In order to fill the gap in the scientific evidence of SDH and make appropriate policies and plans in Iran, it is needed to conduct studies on all SDH according to the WHO conceptual framework. PMID- 26258088 TI - Development of a Universal Safety Behavior Management System for Coal Mine Workers. AB - BACKGROUND: In China, over 80% of all work-related deaths in the mining industry occur in coal mines and human factors constitute 85% of the direct causes of coal mine accidents, which indicates that significant shortcomings currently exist in the safety behavior management of Chinese coal mine workers. We aimed to verify the impact of human psychological behavior in coal mine accidents systematically through experimental study, theoretical analysis and management application. METHODS: Four test instruments (Sensory and cognitive capacity test, Sixteen Personal Factor Questionnaire, Symptom Checklist 90 Questionnaire and the supervisors' evaluation) were employed from November 2013 to June 2014 to identify unsafe behavior factors, the self-established Questionnaire of Safety Behavior Norms (QSBN) was also used to propose the safety behavior countermeasures of coal mine employees. RESULTS: The mental health of most coal mine workers' is relatively poor. The sensory and cognitive capacity of those in different work posts varies greatly, as does the sense of responsibility. Workers are susceptible to external influences, and score low in site management. When the 16-PF and SCL-90 sensory and cognitive assessments were combined, the psychological index predictive power was greatest for estimating sense of efficiency and degree of satisfaction in internal evaluations, while at the same time lowest for estimating control of introversion-extroversion and stress character. CONCLUSION: The psychological indicators can predict part of employee safety behavior, and assist a coal mine enterprise to recruit staff, develop occupational safety norms and improve the working environment. PMID- 26258089 TI - Sensory Impairment and Health-Related Quality of Life. AB - BACKGROUND: Sensory impairment is a common condition that exerts negative effects on health-related quality of life (HRQoL) in the elderly. This study aimed to determine the relationship between sensory impairment and HRQoL and identify sensory-specific differences in the HRQoL of elderly. METHODS: This study used data from the Korean National Health and Nutrition Examination Survey V (2010 2012), analyzing 5,260 subjects over 60 years of age who completed ophthalmic and otologic examinations. Vision and hearing impairment were measured and classified. HRQoL was determined according to the European QoL five dimension test (EQ-5D). Multivariate logistic regression analysis and analysis of covariance were performed to identify relationships between sensory impairment and HRQoL dimensions as well as differences in HRQoL scores. RESULTS: In the final adjusted multivariate model, there was a statistically higher proportion of those with dual sensory impairment who reported problems with mobility (adjusted odds ratio [aOR] 2.30, 95% confidence interval [CI] 1.45-5.03), usual activities (aOR 2.32, 95% CI 1.16-4.64), and pain/discomfort among EQ-5D subcategories (aOR 1.79, 95% CI 1.07-2.97). In the EQ-5D dimensions, the means and standard deviations of vision impairment (0.86 [0.01]) and dual sensory impairment (0.84 [0.02]) appeared meaningfully lower than those for no sensory impairment (0.88 [0.00]) or hearing impairment (0.88 [0.01]); P = .02). CONCLUSION: Sensory impairment reduces HRQoL in the elderly. Improvement of HRQoL in the elderly thus requires regular screening and appropriate management of sensory impairment. PMID- 26258090 TI - Exposure Hazard to Bisphenol A for Labor and Particle Size Distribution at Polycarbonate Molding Plants. AB - BACKGROUND: This research provides an insight into exposure information and particle size distributions of Bisphenol A (BPA), a common environmental hormone, at polycarbonate (PC) molding plants in southern Taiwan. METHODS: The inhalable dust sampler as IOM and the micro-orifice uniform deposition impactor (MOUDI) were used for samples collection to evaluate the level and particle size distribution of BPA in PC molding plants. All collected samples were analyzed by high performance liquid chromatography (HPLC) for BPA concentrations. RESULTS: BPA concentrations detected from the plant using optical grade PC material ranged from 32.28 to 44.97 MUg/m(3), which were significantly higher than BPA concentrations (16.16 to 19.39 MUg/m(3)) detected from the plant using food grade PC material. Under working environment, the particle size distribution showed a single mode distribution, with a MMAD of 0.84MUm and a GSD of 1.97. Emission of BPA increased during heating process and most of BPA particles deposited in the nasal cavity (63.37%), following by alveolus (30.7%), and trachea-bronchus (5.93%). DISCUSSION: It is of importance that proper personal protection should be taken upon the BPA particulates released during the molding process at PC molding plants. PMID- 26258091 TI - Screening of Fetal Chromosome Aneuploidies in the First and Second Trimester of 125,170 Iranian Pregnant Women. AB - BACKGROUND: Aneuploidy is one of the main causes of congenital anomalies, mental and physical disabilities, in newborns. The aim of this study was to determine various chromosomal aneuploidies in the first and second trimester screening of pregnant women, in Iran. METHODS: A descriptive retrospective study was conducted on 125,170 pregnant women referred to a major referral medical diagnostic laboratory (Niloo Laboratory, Tehran) for prenatal screening tests (2010-2013). Patients were divided into 3 groups: first trimester screening (FTS), second trimester screening (STS), and combined screening groups. In positive and borderline cases, and amniocentesis and cytogenetic analysis were carried out. RESULTS: Total prevalence of aneuploidy in 125,170 pregnant women was one in 491, (Detection Rate=82.7% for Down syndrome). The DR for DS in three groups was as follow: 87.5% for FTS (25783 women), 80.9% for STS (91345 women), and 94.7% for combined tests (8042 women). Total number of cases with Edward's syndrome was 18, Patau's syndrome six, Klinefelter syndrome six, triploidy three, and Cri-du-chat syndrome one. CONCLUSION: The present study shows the frequency of aneuploidy in the first and second trimester screenings in a major medical laboratory in Tehran. The prevalence of aneuploidies grows with increased maternal age. The rate of aneuploidy in first trimester is higher than second. PMID- 26258087 TI - Hormones in Dairy Foods and Their Impact on Public Health - A Narrative Review Article. AB - BACKGROUND: The presence of hormones in milk and dairy foods was discussed decades ago but rather more concerns attended to that with respect to finding hormones as biomarkers in milk for diseases and pregnancy diagnosis. Moreover, considerable amount of studies demonstrated that existing of hormones in humans and animals milk are essential for infants growing and immunity. During the last couple of years, increasing body of evidence are indicating another property of hormones in dairy products as possible impact on human health including the role of some estrogens and insulin-like growth factor-1 in initiation and provoking of breast, prostate and endometrial tumours. METHODS: Data was gathered from the published articles in database such as MEDLINE, science direct, Google scholar and web of science. We put no limitation on date of published date. Moreover, our own published and conducted methods and results also are presented. In this review we concentrated on several aspects of presence of hormones in dairy foods with especial emphasize on cow's milk as a major source of consuming milk for humans especially for children. RESULTS: The collected data from other researchers and our own data are indicating that the presence of steroid hormones in dairy products could be counted as an important risk factor for various cancers in humans. CONCLUSION: Our gathered data in this review paper may suggest more sophisticate analytical detection methods for oestrogens determination and also could be considered as a remarkable concern for consumers, producers and public health authorities. PMID- 26258092 TI - Does Supplementation with Royal Jelly Improve Oxidative Stress and Insulin Resistance in Type 2 Diabetic Patients? AB - BACKGROUND: Animal studies have shown antioxidant effects of Royal Jelly (RJ) and its effect on insulin resistance as the most common complication of Type 2 diabetes. This study was conducted to determine the effect of RJ intake on serum total antioxidant capacity, Malondialdehyde and insulin resistance in T2DM. METHODS: In this randomized controlled trial, forty-six type 2 diabetic patients, aged 25-65 years, with BMI of 20-30 kg/m(2), and HbA1c of 6-8% were included. The patients were randomly assigned to receive 1000 mg of RJ supplement or placebo, 3 times daily for 8 weeks. HOMA-IR, anthropometric measurements, fasting blood glucose, serum insulin, total antioxidant capacity and malondialdehyde level were measured. RESULTS: In comparison with placebo, HOMA-IR decreased (P=0.015) while serum total antioxidant capacity increased significantly in RJ group (P=0.016). No significant difference was detected for serum insulin and MDA in two groups. CONCLUSIONS: RJ intake may have favorable effects on serum TAC and HOMA-IR in diabetic patients. PMID- 26258093 TI - Psychological Well-Being (PWB) of School Adolescents Aged 12-18 yr, its Correlation with General Levels of Physical Activity (PA) and Socio-Demographic Factors In Gilgit, Pakistan. AB - BACKGROUND: Adolescence is a critical developmental stage marked by complex transitions. The purpose of study was to assess school adolescents' PWB, examine the relationship of PA and socio-demographic factors with PWB. METHODS: A cross sectional study conducted in five randomly selected schools with 345 adolescents (aged 12-18) from grade 6(th)-10(th). A self-administered Well-Being index was adapted to measure PWB and questionnaire for adolescents PA (PAQ-A). Socio demographic variables determined: age, gender, household income and parental education. Bivariate and multivariate regression analyses performed to examine the association between PWB, PA and covariates. RESULTS: Findings indicated the mean age 14.64 (SD=1.275), 55.4% were female. Without gender difference the majority (43.4%) of adolescents showed moderate, while (23.2%) revealed low level of PWB. Participants with low level likely to have depression but scores were significantly not different between low, moderate and high PWB with PA. Socio demographic trends of adolescents' were observed significant (P <0.005) for PWB. In multivariable analysis the mean wellbeing in females adjusted for other covariates was significant (P =0.004) than males. PWB importantly (P <0.001) decreased by 3.36 units as its covariates increased and PA score in boys found 0.05 unit more than girls. CONCLUSION: The study results are invaluable in addressing low, moderate and high levels of PWB. Inadequate PA and PWB decreasing with some socio-demographic covariates is crucial health issue among female adolescents in Pakistan. Further studies need to find barrier, social indicators of PWB and implication of health among adolescents. PMID- 26258094 TI - Combination Effect of GSTM1, GSTT1 and GSTP1 Polymorphisms and Risk of Systemic Lupus Erythematosus. AB - BACKGROUND: Progression of systemic lupus erythematosus (SLE) could be due to oxidative stress especially through reactive oxygen species (ROS). Detoxification of ROS is largely performed by Glutathione S-transferases (GSTs), therefore polymorphisms of GSTM1, GSTT1 and GSTP1 genes which decrease enzymes activity could affect SLE susceptibility. The aim of this study was to determine the effects of GSTM1 (deletion), GSTT1 (deletion) and GSTP1 (Ile105Val) polymorphisms on SLE susceptibility. METHODS: Genomic DNA was extracted from blood samples of 163 SLE patients and 180 age, sex and ethnically matched controls. GSTs genotypes were determined by polymerase chain reaction (PCR)-multiplex procedure or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: GSTT1 null genotype frequency was higher in SLE patients than controls. NO association observed between GSTM1 null genotype or GSTP1 Ile105Val polymorphism with SLE. Nevertheless combination of GSTT1 null/ GSTM1 null genotypes showed 2.8-fold increase in risk of SLE. Moreover the combination of GSTT1 null/ GSTM1 null/GSTP1 Ile/Val and Val/Val genotypes increased the SLE risk about 8 fold. CONCLUSION: Present data suggest that GSTT1 null/ GSTM1 null/GSTP1 Ile/Val and Val/Val genotypes might largely contribute to the pathogenesis of SLE. PMID- 26258095 TI - Comparison of Indirect Calorimetry and Predictive Equations in Estimating Resting Metabolic Rate in Underweight Females. AB - BACKGROUND: Underweight as a public health problem in young women is associated with nutritional deficiencies, menstrual irregularity, eating disorders, reduced fertility, etc. Since resting metabolic rate (RMR) is a necessary component in the development of nutrition support therapy, therefore we determined the accuracy of commonly used predictive equations against RMR measured by indirect calorimetry among healthy young underweight females. METHODS: This cross sectional study was conducted on 104 underweight females aged 18-30 years old with body mass index (BMI) <18.5 kg/m(2) in 2013. After collecting anthropometric data, body composition was measured by bioelectric impedance analysis (BIA). RMR was measured by using indirect calorimetry (FitMateTM) and was estimated by 10 commonly used predictive equations. Comparisons were conducted using paired t test. The accuracy of the RMR equations was evaluated on the basis of the percentage of subjects' predicted RMR within 10% of measured RMR. RESULTS: The mean BMI of subjects was 17.3+/-1.3 kg/m(2). The measured RMR ranged 736-1490 kcal/day (mean 1084.7+/-175 kcal/day). Findings indicated that except Muller and Abbreviation, other equations significantly over estimated RMR, compared to measured value (P<0.05). As an individual prediction accuracy, these predictive equations showed poor performance with the highest accuracy rate of 54.8% for Muller equation (22.1% under and 23.1% over-prediction) and 43.3% for Abbreviation equation (31.7% under and 25% over-prediction), the percentage bias was 1.8% and 0.63% and RMSE was 162 and 173 kcal/d, respectively. CONCLUSION: Although Muller equation gave fairly acceptable prediction, more suitable new equations are needed to be developed to help better management of nutritional plans in young underweight people. PMID- 26258096 TI - The Evaluation of Multiple Sclerosis Dispersal in Iran and Its Association with Urbanization, Life Style and Industry. AB - BACKGROUND: Multiple Sclerosis (MS) is an autoimmune disease with unknown factor. The prevalence and incidence rate of this disease had an upward trend in many regions in the world such as Middle east and consequently in Iran over the recent years. As the risk factors of this increased trend and high-prevalence is unknown in Iran, the current study has been designed to evaluate the correlation between MS dispersal with urbanization, life style and industry, as an ecological research. METHODS: This retrospective study was designed as an ecological approach in 2011. Data were collected from three databases by high precision (CI95%) from national registry plans. The subjects of study were provinces of Iran (n=31). The linear regression was used to perform statistical analyses. RESULTS: The obtained results indicated an ascendant trend of MS during the recent years, as the incidence of this disease reached from 26.24/100000 (CI95%) people in 2006 to 44.53/100000 (CI95%) in 2011. There is a direct correlation (P<0.05) between the percentage of urbanization and the percentage of male smokers with the prevalence of MS in provinces. CONCLUSION: The role of smoking was more highlighted in this study as a probable factor in increasing risk and causing MS disease. Urbanization could be introduced as an augmentative factor, but this is a combination of several complex factors that this effect must be appraised with smaller scale in other researches. PMID- 26258097 TI - Impact of Education Based on Theory of Planned Behavior: An Investigation into Hypertension-Preventive Self-care Behaviors in Iranian Girl Adolescent. AB - BACKGROUND: Since risk factors of hypertension are formed during adolescent period and regarding that attitudes change occurs more easily in these ages, the present paper aimed to evaluate the impact of education based on the theory of planned behavior in hypertension prevention behaviors in female adolescent students. METHODS: In this quasi-experimental study, 160 girls of 12-16 yr old (80 in each case and control group), who had not been educated in prevention of hypertension over the recent three months, participated. Four schools in Tehran were selected based on cluster sampling method during two stages. The education was provided based on the theory of planned behavior in two sections (nutrition and physical activity) in four sessions. Data gathered before and after education through a two-part valid and reliable questionnaire. The results were analyzed based on SPSS software, version 17. RESULTS: The results of independent t-test showed in the nutrition section, attitude (P=0.000), subjective norm (P=0.025), perceived control (P=0.016) and behavioral intention (P=0.025); significantly increased. About physical activity, except subjective norm (P=0.219), the mean score of the attitude (P=0.001), perceived control (P=0.000) and behavioral intention (P=0.000) revealed a significant difference between two groups. CONCLUSION: Education based on the theory of planned behavior affects the intention of preventive behaviors of hypertension in female adolescents. PMID- 26258098 TI - Regional Disparity in Physical Resources in the Health Sector in Iran: A Comparison of Two Time Periods. AB - BACKGROUND: One of the major health policy issues, in the both developed and developing countries, is the equality in the distribution of health resources. The aim of this study was to investigate the disparity in the distribution of health physical resources across the provinces of Iran in 2001 and 2011. METHODS: This was a cross-sectional retrospective study which investigated inequality in the distribution of health physical resources by three indexes of Gini Coefficient, Gaswirth index and Index of Dissimilarity. The data on provinces were obtained from the yearbook statistics and Ministry of Health, and Medical Education. The Excel software was used to calculated indexes. RESULTS: The finding showed the mean Gini Coefficient for all variables was 0.178 in 2001 and 0.158 in 2011. Besides, the mean Gaswirth index and index of dissimilarity were 11.5 and 1.5% in 2001 and 11 and 1.4% in 2011, respectively. CONCLUSION: There was slightly inequality in distribution of physical health resources in Iran. According to the results of three indexes, this study showed when Tehran province excluding from total sample, the inequality was decreased. PMID- 26258099 TI - The Prevalence and Causes of Visaual Impairment and Blindness in a Rural Population in the North of Iran. AB - BACKGROUND: Visual impairment is a very important public health problem. In Iran, reports of visual impairment and blindness have been published from the urban population while the prevalence of visual impairment in the rural population has not been reported. The purpose of this study to determine the prevalence and causes of visual impairment, in a rural population in district of based on age and sex. METHODS: In a cross-sectional population-based study, using random cluster sampling, 13 of the 83 villages of Khaf County in the north east of Iran were selected. Eye examinations were performed in a Mobile Eye Clinic (Nooravaran Salamat, 2011) and included optometric examinations such as measuring uncorrected and corrected visual acuity along with non-cycloplegic refraction. RESULTS: The prevalence of visual impairment, low vision, and blindness was 6.3% (95% CI 5.3 7.3), 3.4% (95% CI 2.6-4.1), and 3.0% (95% CI 2.3-3.6), respectively. The prevalence of visual impairment ranged from 1.8% in the participant younger than 20 years of age to 28% in the subjects aged 60 and over (P<0.001). After matching for age, the prevalence of visual impairment and low vision was significantly higher in women. The most prevalent causes of visual impairment were uncorrected refractory error (54.5%) and cataract (17.6%). CONCLUSION: The prevalence of visual impairment was significantly higher in the rural population of this study when compared to previous reports from Iran. It seems that provision of therapeutic facilities like cataract surgery and availability of eyeglasses in villages can considerably reduce the prevalence of visual impairment. PMID- 26258100 TI - Detection of Emergence Cyclospora cayetanensis in A HIV(+) / AIDS Patient with Diarrhea from Tehran: A Case Report. AB - Coccidian protozoa of Cyclospora cayetanensis are obligate intracellular apicomplexan parasites that infect the mucosal epithelium of the small intestine of immunocompetent and immunocompromised persons. A 25- years old woman from around, Tehran with complaint of faintness and fatigue with HIV positive/AIDS confirmed eight months ago was admitted in Imam Khomeini Hospital, Tehran, Iran in 2014. The patient suffered from intestinal and lung symptoms like watery diarrhea, flu-like symptoms. The stool was examined by direct preparation and concentration technique, stained with modified acid-fast staining method, and observed with light and then Immunofluorescence microscope. The stool cultivation was made in dichromate potassium medium and diagnosis of Cyclospora infection was finally made according to observation of Cyclospora oocysts almost 10 MUm in acid fast staining method and autofluorescence of Cyclospora under Immunofluorescence microscope. The patient was initially treated with azithromycin, tazocin and fluconazol because of lung lesions and diarrhea and relative remission was observed. Cyclospora sp. causes an intestinal infection particularly in immunocompromised patients. PMID- 26258101 TI - Central Nervous System Aspergilloma in an Immunocompetent Patient: A Case Report. AB - Intracranial aspergilloma is extremely rare. The diagnosis and treatment of invasive CNS aspergillosis is very difficult. Early diagnosis is important for a successful treatment. Here, we report a case of intracranial aspergilloma in an 11-year-old boy in 2013. Good outcome was achieved by treatment with a combination of neurosurgical resection and antifungal administration, which we suggest is a good quality management plan. PMID- 26258102 TI - Comparison of Bacterial Pollution Level According to Sponge Storage Method. PMID- 26258103 TI - Gender Differences in Sociodemographic Correlates with Excessive Television Viewing Time in Taiwanese Older Adults. PMID- 26258104 TI - Helicobacter pylori Related Health Problems in Children. PMID- 26258105 TI - Hepatitis: A Rapidly Spreading Viral Infection in Pakistan. PMID- 26258106 TI - Future Recommendations for School Dental Health Program in India. PMID- 26258107 TI - Can Waist Circumference Be a Reliable Anthropometric Parameter in Healthy Normal Weight and Overweight Adolescents? PMID- 26258108 TI - Evaluation of Shear Bond Strength of Giomer in Comparison with Two Dentin Adhesive Systems. PMID- 26258109 TI - Effectiveness of High Frequency of Two-Year Supervised Brushing with Fluoride Gel in Permanent Teeth in Children from Poland. PMID- 26258110 TI - Prevalence of Minor Psychiatric Disorders and Factors Affecting It in Iranian Nurses. PMID- 26258111 TI - Relationship between family meal frequency and individual dietary intake among diabetic patients. AB - BACKGROUND: Notoriously, the island of Mauritius has one of the highest prevalence of diabetes in the world. Management of the disease is very important and family meals are undoubtedly beneficial to patients as they promote the development of healthy eating behaviours and food choices. This study has aimed to probe into potential relationship(s) between family meal frequency and individual dietary intake among diabetic patients and to establish whether family cohesion may be a plausible mediator of this relationship. METHODS: A cross sectional survey was carried out with a random sample of 384 diabetic patients. The Family Adaptability and Cohesion Evaluation Scale III was used to obtain information on two general aspects of family functioning, that is, cohesiveness and adaptability. Chi-squared (chi (2)) tests, independent sample t-tests and one way ANOVA were used to determine statistical significance. Pearson correlation was used to examine associations between family meal frequency, individual dietary intake and family cohesion. Hierarchical linear regression models were performed for the mediation analysis. RESULTS: Family meal frequency (breakfast, lunch and dinner) was observed to be positively associated with intake of fish, raw vegetables, dried and fresh fruits, low-fat milk, cheese, yogurt, nuts and light butter and negatively associated with intake of red meat, white rice, white bread, whole egg fried, chocolates, fried cakes, burgers, chips, and fried noodles/rice. Average mediation (52.6 %) was indicated by family cohesion for the association between family meal frequency and individual dietary intake among diabetic patients. Sobel's test further confirmed the trend towards complete mediation (z = 15.4; P < 0.05). CONCLUSIONS: A strong relationship between family meal frequency and individual dietary intake among diabetic patients was recorded. The present study is one of the few studies that have examined family cohesion as a mediator of the relationship and to our best knowledge is the first work to demonstrate a trend towards complete mediation. Results obtained can be used by health professionals to devise strategies for increasing knowledge and awareness of both diabetic patients and their respective families to curd down this public health burden. PMID- 26258112 TI - PRECISION IN ESTIMATES OF DISABILITY PREVALENCE FOR THE POPULATION AGED 65 AND OVER IN THE UNITED STATES BY RACE AND ETHNICITY. AB - BACKGROUND: Populations are aging worldwide. In the United States (US), the older adult (aged >=65) population will increase rapidly in the decades to come. Identifying public health needs in older adults requires that sample-derived estimates of disability prevalence be produced using transparent methodologies. OBJECTIVES: Produce estimates of disabilities for the US older adult population by race and ethnicity and present measures on the 'level of precision' in the estimates. DESIGN: Cross-sectional study used American Community Survey (ACS) Public Use Microdata Sample (PUMS) 3-year file collected during 2009-2011 survey period. SETTING: Community dwelling population aged >=65 in US. PARTICIPANTS: The 1,494,893 actual survey participants (unweighted count) are said to represent 40,496,512 individuals after population weights are applied (weighted count). From the weighted counts, the average age is 75, about 56% are females, and most (80%) are Non-Latino-Whites (NLW). RESULTS: Qualitative comparisons provide some evidence that except for hearing, disability prevalence is highest in Non-Latino Blacks along the following disability items: independent living (25%); ambulatory (34%); self-care (15%); cognitive (11%); and vision (11%). Person inflation ratios, width of 95% confidence interval, and rates of allocations are smaller in NLWs than all the other race-ethnic groups-suggesting disability estimates for NLWs merit the highest level of confidence. CONCLUSIONS: Improving measures of health in the older adult population requires that efforts continue to highlight how estimates of disability prevalence have the potential to vary in precision and as a function of various known and unknown factors. PMID- 26258113 TI - INTERSECTING SELF-REPORTED MOBILITY AND GAIT SPEED TO CREATEA MULTI-DIMENSIONAL MEASURE OF AMBULATION: THE "AMBULATION SPEED-ENDURANCE" (ASE) TYPOLOGY. AB - BACKGROUND: Assessing mobility through readily available and affordable protocols may help advance public health by providing early detection and implementing intervention therapies aimed at mitigating the progression from physiological vitality to disability at older ages. Until now, little attention has been given to how self-reported mobility (SRM) and gait speed can be combined in a categorization scheme. OBJECTIVES: The specific aim of this report is to introduce the Ambulation Speed-Endurance (ASE) Typology to the literature-a classification system that intersects SRM and gait speed to create a multi dimensional measure of ambulation. DESIGN: Cross-sectional. SETTING: Community dwelling older adults in the United States. PARTICIPANTS: Evidence is provided from the National Health and Aging Trends Study (NHATS) that community-dwelling older adults (n=5,403) may be found in each of the ASE Typologies. The discussion is complimented by investigating the cross-sectional predictors of a "Discrepancy Score" (measure of gap between speed and endurance) amongst those with gait speeds < 0.99 m/sec (n=4,521). RESULTS: Multivariable linear regression results indicate level of severity in speed-endurance discrepancy is higher amongst: non Latino-Blacks (beta=0.48); Latinos (beta=0.42); older ages; and lower educated. Models also show that severity in speed-endurance discrepancy is lower amongst: females (beta=-0.38); those with higher body mass index; with more chronic health conditions; and poorer self-rated health. CONCLUSION: Research should continue to investigate how to optimize SRM. PMID- 26258114 TI - A novel method for the management of proximal segment using computer assisted simulation surgery: correct condyle head positioning and better proximal segment placement. AB - Computer Assisted Simulation Surgery (CASS) is a reliable method that permits oral and maxillofacial surgeons to visualize the position of the maxilla and the mandible as observed in the patient. The purpose of this report was to introduce a newly developed strategy for proximal segment management according to Balanced Orthognathic Surgery (BOS) protocol which is a type of CASS, and to establish the clinical feasibility of the BOS protocol in the treatment of complex maxillo facial deformities. The BOS protocol consists of the following 4 phases: 1) Planning and simulation phase, 2) Modeling phase, 3) Surgical phase, and 4) Evaluation phase. The surgical interventions in 80 consecutive patients were planned and executed by the BOS protocol. The BOS protocol ensures accuracy during surgery, thereby facilitating the completion of procedures without any complications. The BOS protocol may be a complete solution that enables an orthognatic surgeon to perform accurate surgery based on a surgical plan, making real outcomes as close to pre-planned outcomes as possible. PMID- 26258115 TI - Successful and rapid response of speech bulb reduction program combined with speech therapy in velopharyngeal dysfunction: a case report. AB - Velopharyngeal dysfunction in cleft palate patients following the primary palate repair may result in nasal air emission, hypernasality, articulation disorder and poor intelligibility of speech. Among conservative treatment methods, speech aid prosthesis combined with speech therapy is widely used method. However because of its long time of treatment more than a year and low predictability, some clinicians prefer a surgical intervention. Thus, the purpose of this report was to increase an attention on the effectiveness of speech aid prosthesis by introducing a case that was successfully treated. In this clinical report, speech bulb reduction program with intensive speech therapy was applied for a patient with velopharyngeal dysfunction and it was rapidly treated by 5months which was unusually short period for speech aid therapy. Furthermore, advantages of pre operative speech aid therapy were discussed. PMID- 26258116 TI - Approaches to Managing Autoimmune Cytopenias in Novel Immunological Disorders with Genetic Underpinnings Like Autoimmune Lymphoproliferative Syndrome. AB - Autoimmune lymphoproliferative syndrome (ALPS) is a rare disorder of apoptosis. It is frequently caused by mutations in FAS (TNFRSF6) gene. Unlike most of the self-limiting autoimmune cytopenias sporadically seen in childhood, multi lineage cytopenias due to ALPS are often refractory, as their inherited genetic defect is not going to go away. Historically, more ALPS patients have died due to overwhelming sepsis following splenectomy to manage their chronic cytopenias than due to any other cause, including malignancies. Hence, current recommendations underscore the importance of avoiding splenectomy in ALPS, by long-term use of corticosteroid-sparing immunosuppressive agents like mycophenolate mofetil and sirolimus. Paradigms learnt from managing ALPS patients in recent years is highlighted here and can be extrapolated to manage refractory cytopenias in patients with as yet undetermined genetic bases for their ailments. It is also desirable to develop international registries for children with rare and complex immune problems associated with chronic multilineage cytopenias in order to elucidate their natural history and long-term comorbidities due to the disease and its treatments. PMID- 26258117 TI - "Living in a Communal Garden" Associated with Well-Being While Reducing Urban Sprawl by 40%: A Mixed-Methods Cross-Sectional Study. AB - BACKGROUND: The extent to which novel land-efficient neighborhood design can promote key health behaviors is examined, concentrating on communal outdoor space provision (COSP). OBJECTIVES: To test whether a neighborhood (Accordia) with a higher ratio of communal to private outdoor space is associated with higher levels of resident's (a) self-reported local health behaviors and (b) observed engagement in local health behaviors, compared to a matched neighborhood with lower proportion of COSP. METHODS: Health behaviors were examined via direct observation and postal survey. Bespoke observation codes and survey items represented key well-being behaviors including "connecting," "keeping active," "taking notice," "keep learning," and "giving." The questionnaire was validated using psychometric analyses and observed behaviors were mapped in real-time. RESULTS: General pursuit of health behaviors was very similar in both areas but Accordia residents reported substantially greater levels of local activity. Validated testing of survey dataset (n = 256) showed support for a stronger Attitude to Neighborhood Life (connecting and giving locally) in Accordia and partial support of greater physical activity. Analyses of the behavior observation dataset (n = 7,298) support the self-reported findings. Mapped observations revealed a proliferation of activity within Accordia's innovative outdoor hard spaces. CONCLUSION: Representation is limited to upper-middle class UK groups. However, Accordia was found to promote health behaviors compared a traditional neighborhood that demands considerably more land area. The positive role of home zone streets, hard-standing and semi-civic space highlights the principle of quality as well as quantity. The findings should be considered as part of three forthcoming locally led UK garden cities, to be built before 2020. PMID- 26258119 TI - Nanoparticle separation with a miniaturized asymmetrical flow field-flow fractionation cartridge. AB - Asymmetrical Flow Field-Flow Fractionation (AF4) is a separation technique applicable to particles over a wide size range. Despite the many advantages of AF4, its adoption in routine particle analysis is somewhat limited by the large footprint of currently available separation cartridges, extended analysis times and significant solvent consumption. To address these issues, we describe the fabrication and characterization of miniaturized AF4 cartridges. Key features of the down-scaled platform include simplified cartridge and reagent handling, reduced analysis costs and higher throughput capacities. The separation performance of the miniaturized cartridge is assessed using certified gold and silver nanoparticle standards. Analysis of gold nanoparticle populations indicates shorter analysis times and increased sensitivity compared to conventional AF4 separation schemes. Moreover, nanoparticulate titanium dioxide populations exhibiting broad size distributions are analyzed in a rapid and efficient manner. Finally, the repeatability and reproducibility of the miniaturized platform are investigated with respect to analysis time and separation efficiency. PMID- 26258118 TI - Synthesis of lysine methyltransferase inhibitors. AB - Lysine methyltransferase which catalyze methylation of histone and non-histone proteins, play a crucial role in diverse biological processes and has emerged as a promising target for the development of various human diseases, including cancer, inflammation, and psychiatric disorders. However, inhibiting lysine methyltransferases selectively has presented many challenges to medicinal chemists. During the past decade, lysine methyltransferase inhibitors covering many different structural classes have been designed and developed. In this review, we describe the development of selective, small-molecule inhibitors of lysine methyltransferases with an emphasis on their discovery and chemical synthesis. We highlight the current state of lysine methyltransferase inhibitors and discuss future directions and opportunities for lysine methyltransferase inhibitor discovery. PMID- 26258120 TI - Seed dormancy is modulated in recently evolved chlorsulfuron-resistant Turkish biotypes of wild mustard (Sinapis arvensis). AB - Biotypes of the broad-leaved wild mustard (Sinapis arvensis L.) found in wheat fields of Aegean and Marmara region of Turkey were characterized and shown to have developed resistance to sulfonylurea (chlorsulfuron), an inhibitor of acetolactate synthase (ALS). DNA sequence analysis of the ALS genes from two such resistant ("R") biotypes, KNF-R1 and KNF-R2, revealed point mutations, CCT (Pro 197) to TCT (Ser 197) in KNF-R1 and CCT (Pro 197) to ACT (Thr 197) in KNF-R2; these substitutions are consistent with the presence of chlorsulfuron-insensitive ALS enzyme activity in the "R" S. arvensis biotypes. An additional phenotype of chlorsulfuron resistance in the Turkish S. arvensis "R" biotypes was revealed in the form of an altered seed dormancy behavior over 4-48 months of dry storage (after-ripening) compared to the susceptible ("S") biotypes. Seeds of the "S" biotypes dry stored for 4 months had a higher initial germination, which sharply decreased with storage time, while the seeds of the "R" biotypes had lower germination after 4-months storage, rising sharply and peaking thereafter by 24 months' of dry storage. The "R" biotype seeds continued to maintain a higher germination percentage even after 48 months of after-ripening. The seed weight of "R" and "S" biotypes after-ripened for 4 months was similar but those after ripened for 48 months differed, "R" seeds were significantly heavier than those of the "S" seeds. Differential seed germinability between "S" and "R" biotypes was found not a case of differential viability, temperature regimen or non response to pro-germination hormone GA3. These studies are of relevance to ecological fitness of herbicide-resistant biotypes in terms of seed viability and germination. PMID- 26258121 TI - Identification and Molecular Characterization of the Switchgrass AP2/ERF Transcription Factor Superfamily, and Overexpression of PvERF001 for Improvement of Biomass Characteristics for Biofuel. AB - The APETALA2/ethylene response factor (AP2/ERF) superfamily of transcription factors (TFs) plays essential roles in the regulation of various growth and developmental programs including stress responses. Members of these TFs in other plant species have been implicated to play a role in the regulation of cell wall biosynthesis. Here, we identified a total of 207 AP2/ERF TF genes in the switchgrass genome and grouped into four gene families comprised of 25 AP2-, 121 ERF-, 55 DREB (dehydration responsive element binding)-, and 5 RAV (related to API3/VP) genes, as well as a singleton gene not fitting any of the above families. The ERF and DREB subfamilies comprised seven and four distinct groups, respectively. Analysis of exon/intron structures of switchgrass AP2/ERF genes showed high diversity in the distribution of introns in AP2 genes versus a single or no intron in most genes in the ERF and RAV families. The majority of the subfamilies or groups within it were characterized by the presence of one or more specific conserved protein motifs. In silico functional analysis revealed that many genes in these families might be associated with the regulation of responses to environmental stimuli via transcriptional regulation of the response genes. Moreover, these genes had diverse endogenous expression patterns in switchgrass during seed germination, vegetative growth, flower development, and seed formation. Interestingly, several members of the ERF and DREB families were found to be highly expressed in plant tissues where active lignification occurs. These results provide vital resources to select candidate genes to potentially impart tolerance to environmental stress as well as reduced recalcitrance. Overexpression of one of the ERF genes (PvERF001) in switchgrass was associated with increased biomass yield and sugar release efficiency in transgenic lines, exemplifying the potential of these TFs in the development of lignocellulosic feedstocks with improved biomass characteristics for biofuels. PMID- 26258122 TI - Automatic Evaluation of Speech Rhythm Instability and Acceleration in Dysarthrias Associated with Basal Ganglia Dysfunction. AB - Speech rhythm abnormalities are commonly present in patients with different neurodegenerative disorders. These alterations are hypothesized to be a consequence of disruption to the basal ganglia circuitry involving dysfunction of motor planning, programing, and execution, which can be detected by a syllable repetition paradigm. Therefore, the aim of the present study was to design a robust signal processing technique that allows the automatic detection of spectrally distinctive nuclei of syllable vocalizations and to determine speech features that represent rhythm instability (RI) and rhythm acceleration (RA). A further aim was to elucidate specific patterns of dysrhythmia across various neurodegenerative disorders that share disruption of basal ganglia function. Speech samples based on repetition of the syllable /pa/ at a self-determined steady pace were acquired from 109 subjects, including 22 with Parkinson's disease (PD), 11 progressive supranuclear palsy (PSP), 9 multiple system atrophy (MSA), 24 ephedrone-induced parkinsonism (EP), 20 Huntington's disease (HD), and 23 healthy controls. Subsequently, an algorithm for the automatic detection of syllables as well as features representing RI and RA were designed. The proposed detection algorithm was able to correctly identify syllables and remove erroneous detections due to excessive inspiration and non-speech sounds with a very high accuracy of 99.6%. Instability of vocal pace performance was observed in PSP, MSA, EP, and HD groups. Significantly increased pace acceleration was observed only in the PD group. Although not significant, a tendency for pace acceleration was observed also in the PSP and MSA groups. Our findings underline the crucial role of the basal ganglia in the execution and maintenance of automatic speech motor sequences. We envisage the current approach to become the first step toward the development of acoustic technologies allowing automated assessment of rhythm in dysarthrias. PMID- 26258124 TI - Clinical and Survival Impact of FDG PET in Patients with Suspicion of Recurrent Ovarian Cancer: A 6-Year Follow-Up. AB - BACKGROUND: The aim of this retrospective study was to evaluate the contribution of fluorine-18-fluoro-deoxyglucose (FDG) positron emission tomography (PET) to the clinical management and survival outcome of patients (pts) suspected of recurrent ovarian carcinoma, with the hypothesis that early diagnosis of recurrent ovarian cancer may improve overall survival (OS). METHODS: Fifty-three FDG PET/CT scans were retrospectively analyzed for 42 pts. CT and PET/CT findings were confirmed by imaging and clinical follow-up, and/or pathology, which were considered as the gold standard diagnosis. The treatment plan based on CT staging was compared with that based on PET/CT findings. Medical records were reviewed for pts characteristics, progression-free survival (PFS), and OS. PFS and OS were analyzed using the Cox proportional hazards regression model. RESULTS: The final diagnosis of recurrence was established pathologically (n = 16), or by a median clinical follow-up of 6.5 years (range 0.5-7.5) after the PET/CT (n = 37). PET/CT provided a higher detection sensitivity (92.2%, 47/51) than CT (60.8%, 31/51) (p < 0.001). Globally, PET/CT modified the treatment plan in 56.6% (30/53) and in 65.2% (15/23) when the CT was negative prior to PET/CT. In 30 cases, those benefited from a modified treatment plan, these changes led to the intensification of a previous treatment procedure in 83.3% (25/30), and to a reduction in the previous treatment procedure in 16.6% of cases (5/30). The Cox regression multivariate analysis showed that the number of lesions visualized by CT and presence of lung lesions detected by PET/CT were significantly associated with PFS (p = 0.002 and p = 0.035, respectively). CONCLUSION: On account of its impact on treatment planning, and especially in predicting patient outcome, FDG PET is a valuable diagnostic tool for cases of suspected ovarian cancer recurrence. PMID- 26258123 TI - Hypoxia signaling pathways: modulators of oxygen-related organelles. AB - Oxygen (O2) is an essential substrate in cellular metabolism, bioenergetics, and signaling and as such linked to the survival and normal function of all metazoans. Low O2 tension (hypoxia) is a fundamental feature of physiological processes as well as pathophysiological conditions such as cancer and ischemic diseases. Central to the molecular mechanisms underlying O2 homeostasis are the hypoxia-inducible factors-1 and -2 alpha (HIF-1alpha and EPAS1/HIF-2alpha) that function as master regulators of the adaptive response to hypoxia. HIF-induced genes promote characteristic tumor behaviors, including angiogenesis and metabolic reprogramming. The aim of this review is to critically explore current knowledge of how HIF-alpha signaling regulates the abundance and function of major O2-consuming organelles. Abundant evidence suggests key roles for HIF 1alpha in the regulation of mitochondrial homeostasis. An essential adaptation to sustained hypoxia is repression of mitochondrial respiration and induction of glycolysis. HIF-1alpha activates several genes that trigger mitophagy and represses regulators of mitochondrial biogenesis. Several lines of evidence point to a strong relationship between hypoxia, the accumulation of misfolded proteins in the endoplasmic reticulum, and activation of the unfolded protein response. Surprisingly, although peroxisomes depend highly on molecular O2 for their function, there has been no evidence linking HIF signaling to peroxisomes. We discuss our recent findings that establish HIF-2alpha as a negative regulator of peroxisome abundance and suggest a mechanism by which cells attune peroxisomal function with O2 availability. HIF-2alpha activation augments peroxisome turnover by pexophagy and thereby changes lipid composition reminiscent of peroxisomal disorders. We discuss potential mechanisms by which HIF-2alpha might trigger pexophagy and place special emphasis on the potential pathological implications of HIF-2alpha-mediated pexophagy for human health. PMID- 26258125 TI - Exosomic microRNAs in the Tumor Microenvironment. AB - Dissecting the crosstalk between tumor cells and tumor microenvironment is quickly becoming the new frontier in cancer research. It is now widely accepted that cancer cells can exert a profound influence over their surroundings, by changing the microenvironment from a normal to a tumor-supportive state that allows for sustained tumor growth, invasion, and drug resistance. Extracellular vesicles, especially exosomes, are recognized as a new category of intercellular communicator, and they are emerging as of primary importance in controlling the interplay between the tumor and its environment. Exosomes derived from cancer cells or from cells of the tumor microenvironment allow for the horizontal transfer of information by virtue of their cargo, made of functional proteins and nucleic acids that are specifically sorted and loaded in exosomes during their biogenesis. In this review, we will discuss the current knowledge regarding the role invested by microRNAs, a family of short non-coding RNAs frequently deregulated in malignancies and present in exosomes, in shaping the microenvironment in a cancer-dependent manner. PMID- 26258127 TI - Bridging Basic Science with Cardiac Surgery: The Bristol Heart Institute Experience. PMID- 26258128 TI - Integrated Anterior, Central, and Posterior Skull Base Unit - A New Perspective. AB - The skull base is one of the most complex anatomical regions and forms the floor of the cranial cavity. Skull base surgery involves open, microscopic, and endoscopic approaches to the anterior, middle, or posterior cranial fossa. A multispecialty team approach is essential in treating patients with skull base lesions. Traditionally, rhinologists are involved in providing access to anterior skull base lesions while otologists are involved in the treatment of lesions of the posterior skull base. This is the case in most skull base centers today. In this article, we share a new perspective of an integrated skull base unit where a team of otolaryngologists and neurosurgeons treat anterior, middle, and posterior skull base pathologies. The rationale for this approach is that most technical skills required in skull base surgery are interchangeable and apply whether an endoscopic or microscopic approach is used. We show how the different skills apply to the different approaches and share our experience with an integrated skull base unit. PMID- 26258126 TI - The L-Cell in Nutritional Sensing and the Regulation of Appetite. AB - The gastrointestinal (GI) tract senses the ingestion of food and responds by signaling to the brain to promote satiation and satiety. Representing an important part of the gut-brain axis, enteroendocrine L-cells secrete the anorectic peptide hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) in response to the ingestion of food. The release of GLP-1 has multiple effects, including the secretion of insulin from pancreatic beta-cells, decreased gastric emptying, and increased satiation. PYY also slows GI motility and reduces food intake. At least part of the gut-brain response seems to be due to direct sensing of macronutrients by L-cells, by mechanisms including specific nutrient-sensing receptors. Such receptors may represent possible pathways to target to decrease appetite and increase energy expenditure. Designing drugs or functional foods to exploit the machinery of these nutrient-sensing mechanisms may offer a potential approach for agents to treat obesity and metabolic disease. PMID- 26258129 TI - Advanced Imaging in Femoroacetabular Impingement: Current State and Future Prospects. AB - Symptomatic femoroacetabular impingement (FAI) is now a known precursor of early osteoarthritis (OA) of the hip. In terms of clinical intervention, the decision between joint preservation and joint replacement hinges on the severity of articular cartilage degeneration. The exact threshold during the course of disease progression when the cartilage damage is irreparable remains elusive. The intention behind radiographic imaging is to accurately identify the morphology of osseous structural abnormalities and to accurately characterize the chondrolabral damage as much as possible. However, both plain radiographs and computed tomography (CT) are insensitive for articular cartilage anatomy and pathology. Advanced magnetic resonance imaging (MRI) techniques include magnetic resonance arthrography and biochemically sensitive techniques of delayed gadolinium enhanced MRI of cartilage (dGEMRIC), T1rho (T1rho), T2/T2* mapping, and several others. The diagnostic performance of these techniques to evaluate cartilage degeneration could improve the ability to predict an individual patient-specific outcome with non-surgical and surgical care. This review discusses the facts and current applications of biochemical MRI for hip joint cartilage assessment covering the roles of dGEMRIC, T2/T2*, and T1rho mapping. The basics of each technique and their specific role in FAI assessment are outlined. Current limitations and potential pitfalls as well as future directions of biochemical imaging are also outlined. PMID- 26258130 TI - The primary photoreaction of channelrhodopsin-1: wavelength dependent photoreactions induced by ground-state heterogeneity. AB - The primary photodynamics of channelrhodopsin-1 from Chlamydomonas augustae (CaChR1) was investigated by VIS-pump supercontinuum probe experiments from femtoseconds to 100 picoseconds. In contrast to reported experiments on channelrhodopsin-2 from Chlamydomonas reinhardtii (CrChR2), we found a clear dependence of the photoreaction dynamics on varying the excitation wavelength. Upon excitation at 500 and at 550 nm we detected different bleaching bands, and spectrally distinct photoproduct absorptions in the first picoseconds. We assign the former to the ground-state heterogeneity of a mixture of 13-cis and all-trans retinal maximally absorbing around 480 and 540 nm, respectively. At 550 nm, all trans retinal of the ground state is almost exclusively excited. Here, we found a fast all-trans to 13-cis isomerization process to a hot and spectrally broad P1 photoproduct with a time constant of (100 +/- 50) fs, followed by photoproduct relaxation with time constants of (500 +/- 100) fs and (5 +/- 1) ps. The remaining fraction relaxes back to the parent ground state with time constants of (500 +/- 100) fs and (5 +/- 1) ps. Upon excitation at 500 nm a mixture of both chromophore conformations is excited, resulting in overlapping reaction dynamics with additional time constants of <300 fs, (1.8 +/- 0.3) ps and (90 +/- 25) ps. A new photoproduct Q is formed absorbing at around 600 nm. Strong coherent oscillatory signals were found pertaining up to several picoseconds. We determined low frequency modes around 200 cm(-1), similar to those reported for bacteriorhodopsin. PMID- 26258131 TI - Evidence for Broadening Criteria for Atypical Depression Which May Define a Reactive Depressive Disorder. AB - Objective. Arguing that additional symptoms should be added to the criteria for atypical depression. Method. Published research articles on atypical depression are reviewed. Results. (1) The original studies upon which the criteria for atypical depression were based cited fatigue, insomnia, pain, and loss of weight as characteristic symptoms. (2) Several studies of DSM depressive criteria found patients with atypical depression to exhibit high levels of insomnia, fatigue, and loss of appetite/weight. (3) Several studies have found atypical depression to be comorbid with headaches, bulimia, and body image issues. (4) Most probands who report atypical depression meet criteria for "somatic depression," defined as depression associated with several of disordered eating, poor body image, headaches, fatigue, and insomnia. The gender difference in prevalence of atypical depression results from its overlap with somatic depression. Somatic depression is associated with psychosocial measures related to gender, linking it with the descriptions of atypical depression as "reactive" appearing in the studies upon which the original criteria for atypical depression were based. Conclusion. Insomnia, disordered eating, poor body image, and aches/pains should be added as criteria for atypical depression matching criteria for somatic depression defining a reactive depressive disorder possibly distinct from endogenous melancholic depression. PMID- 26258132 TI - Genetic Geostatistical Framework for Spatial Analysis of Fine-Scale Genetic Heterogeneity in Modern Populations: Results from the KORA Study. AB - Aiming to investigate fine-scale patterns of genetic heterogeneity in modern humans from a geographic perspective, a genetic geostatistical approach framed within a geographic information system is presented. A sample collected for prospective studies in a small area of southern Germany was analyzed. None indication of genetic heterogeneity was detected in previous analysis. Socio demographic and genotypic data of German citizens were analyzed (212 SNPs; n = 728). Genetic heterogeneity was evaluated with observed heterozygosity (H O ). Best-fitting spatial autoregressive models were identified, using socio demographic variables as covariates. Spatial analysis included surface interpolation and geostatistics of observed and predicted patterns. Prediction accuracy was quantified. Spatial autocorrelation was detected for both socio demographic and genetic variables. Augsburg City and eastern suburban areas showed higher H O values. The selected model gave best predictions in suburban areas. Fine-scale patterns of genetic heterogeneity were observed. In accordance to literature, more urbanized areas showed higher levels of admixture. This approach showed efficacy for detecting and analyzing subtle patterns of genetic heterogeneity within small areas. It is scalable in number of loci, even up to whole-genome analysis. It may be suggested that this approach may be applicable to investigate the underlying genetic history that is, at least partially, embedded in geographic data. PMID- 26258133 TI - Effects of Surface Inclination on the Vertical Loading Rates and Landing Pattern during the First Attempt of Barefoot Running in Habitual Shod Runners. AB - Barefoot running has been proposed to reduce vertical loading rates, which is a risk factor of running injuries. Most of the previous studies evaluated runners on level surfaces. This study examined the effect of surface inclination on vertical loading rates and landing pattern during the first attempt of barefoot running among habitual shod runners. Twenty habitual shod runners were asked to run on treadmill at 8.0 km/h at three inclination angles (0 degrees ; +10 degrees ; -10 degrees ) with and without their usual running shoes. Vertical average rate (VALR) and instantaneous loading rate (VILR) were obtained by established methods. Landing pattern was decided using high-speed camera. VALR and VILR in shod condition were significantly higher (p < 0.001) in declined than in level or inclined treadmill running, but not in barefoot condition (p > 0.382). There was no difference (p > 0.413) in the landing pattern among all surface inclinations. Only one runner demonstrated complete transition to non-heel strike landing in all slope conditions. Reducing heel strike ratio in barefoot running did not ensure a decrease in loading rates (p > 0.15). Conversely, non-heel strike landing, regardless of footwear condition, would result in a softer landing (p < 0.011). PMID- 26258134 TI - Musculoskeletal Injuries and Training Patterns in Junior Elite Orienteering Athletes. AB - Findings about the relation between musculoskeletal injuries and training patterns in orienteering athletes are sparse. Therefore, the musculoskeletal injuries and training patterns of 31 Swiss elite orienteering athletes aged 18-19 years were analyzed in a retrospective study. Individual training diaries and medical records were used to assess training data and injury history, respectively. Group comparisons and a multiple linear regression (MLR) were performed for statistical analysis. The junior elite orienteering athletes performed 7.38 +/- 2.00 training sessions weekly, with a total duration of 455.75 +/- 98.22 minutes. An injury incidence rate (IIR) of 2.18 +/- 2.13 injuries per 1000 hours of training was observed. The lower extremity was affected in 93% of all injuries, and the knee (33%) was the most commonly injured location. The MLR revealed that gender and six training variables explained 60% of the variance in the injury severity index in this study. Supported by the low IIR in the observed age group, the training protocol of the junior elite orienteering athletes was generally adequate. In comparison to elite track, marathon, and orienteering athletes, the junior elite athletes performed less high-intensity interval training (HIIT). However, more frequent HIIT seems to be a protective factor against injuries. PMID- 26258135 TI - Genetic Variation, Heritability, and Diversity Analysis of Upland Rice (Oryza sativa L.) Genotypes Based on Quantitative Traits. AB - Upland rice is important for sustainable crop production to meet future food demands. The expansion in area of irrigated rice faces limitations due to water scarcity resulting from climate change. Therefore, this research aimed to identify potential genotypes and suitable traits of upland rice germplasm for breeding programmes. Forty-three genotypes were evaluated in a randomised complete block design with three replications. All genotypes exhibited a wide and significant variation for 22 traits. The highest phenotypic and genotypic coefficient of variation was recorded for the number of filled grains/panicle and yields/plant (g). The highest heritability was found for photosynthetic rate, transpiration rate, stomatal conductance, intercellular CO2, and number of filled grains/panicle and yields/plant (g). Cluster analysis based on 22 traits grouped the 43 rice genotypes into five clusters. Cluster II was the largest and consisted of 20 genotypes mostly originating from the Philippines. The first four principle components of 22 traits accounted for about 72% of the total variation and indicated a wide variation among the genotypes. The selected best trait of the number of filled grains/panicle and yields/plant (g), which showed high heritability and high genetic advance, could be used as a selection criterion for hybridisation programmes in the future. PMID- 26258136 TI - Influence of Pelvic Tilt on Polyethylene Wear after Total Hip Arthroplasty. AB - We aimed to evaluate the effects of pelvic tilt on polyethylene wear after total hip arthroplasty (THA). A total of 105 joints treated with primary THA were included; conventional polyethylene (CPE) liners were used in 43 hips and highly cross-linked polyethylene (HXLPE) liners were used in the remaining 62 hips. The pelvis was tilted 6 degrees posteriorly in the standing position as compared to the supine position, which resulted in significant increases of 1.7 degrees and 2.8 degrees in cup inclination in the CPE and HXLPE groups, respectively. Moreover, the change in pelvic tilt resulted in significant increases of 3.6 degrees and 4.9 degrees in cup anteversion in the CPE and HXLPE groups, respectively. For the CPE group, multiple regression analysis showed a significant association between the angle of pelvic tilt (PTA) and cup inclination and the polyethylene wear ratio. The adjusted R (2) of the regression model was larger for measures obtained in the standing position as compared to the supine position. For the HXLPE group, there was no significant relationship between radiographic parameters and polyethylene wear. Close observation of polyethylene wear is recommended for patients with severe posterior pelvic tilt who have undergone THA with conventional polyethylene. PMID- 26258137 TI - Experience of Preimplantation Genetic Diagnosis for Hemophilia at the University Hospital Virgen Del Rocio in Spain: Technical and Clinical Overview. AB - Hemophilia A and B are the most common hereditary hemorrhagic disorders, with an X-linked mode of inheritance. Reproductive options for the families affected with hemophilia, aiming at the prevention of the birth of children with severe coagulation disorders, include preimplantation genetic diagnosis (PGD). Here we present the results of our PGD Program applied to hemophilia, at the Department of Genetics, Reproduction and Fetal Medicine of the University Hospital Virgen del Rocio in Seville. A total of 34 couples have been included in our program since 2005 (30 for hemophilia A and 4 for hemophilia B). Overall, 60 cycles were performed, providing a total of 508 embryos. The overall percentage of transfers per cycle was 81.7% and the live birth rate per cycle ranged from 10.3 to 24.1% depending on the methodological approach applied. Although PGD for hemophilia can be focused on gender selection of female embryos, our results demonstrate that methodological approaches that allow the diagnosis of the hemophilia status of every embryo have notorious advantages. Our PGD Program resulted in the birth of 12 healthy babies for 10 out of the 34 couples (29.4%), constituting a relevant achievement for the Spanish Public Health System within the field of haematological disorders. PMID- 26258138 TI - Acoustic Radiation Force Impulse Technology in the Differential Diagnosis of Solid Breast Masses with Different Sizes: Which Features Are Most Efficient? AB - PURPOSE: To evaluate diagnostic performance of acoustic radiation force impulse (ARFI) technology for solid breast masses with different sizes and determine which features are most efficient. MATERIALS AND METHODS: 271 solid breast masses in 242 women were examined with ARFI, and their shear wave velocities (SWVs), Virtual Touch tissue imaging (VTI) patterns, and area ratios (ARs) were measured and compared with their histopathological outcomes. Receiver operating characteristic curves (ROC) were calculated to assess diagnostic performance of ARFI for small masses (6-14 mm) and big masses (15-30 mm). RESULTS: SWV of mass was shown to be positively associated with mass size (P < 0.001). For small masses, area under ROC (Az) of AR was larger than that of SWV (P < 0.001) and VTI pattern (P < 0.001); no significant difference was found between Az of SWV and that of VTI pattern (P = 0.906). For big masses, Az of VTI pattern was less than that of SWV (P = 0.008) and AR (P = 0.002); no significant difference was identified between Az of SWV and that of AR (P = 0.584). CONCLUSIONS: For big masses, SWV and AR are both efficient measures; nevertheless, for small masses, AR seems to be the best feature. PMID- 26258139 TI - Clinical Outcome after Colonic Resection in Women with Endometriosis. AB - BACKGROUND: In severe forms of endometriosis, the colon or rectum may be involved. This study evaluated the functional results and long-term outcome after laparoscopic colonic resection for endometriosis. PATIENTS AND METHODS: Questionnaire survey with 24 women who had experienced typical symptoms, including pelvic pain, infertility, and endometriotic lesions in the bowel and undergone laparoscopic surgery, including low anterior resection, from 2009 to 2012, was conducted. RESULTS: Information about the postoperative outcome was obtained from 22 women and was analyzed statistically. Twenty-one had undergone low anterior resection; one patient required a primary Hartmann procedure due to a rectovaginal fistula. The conversion rate was 4.5%. Major complications occurred in one patient, including an anastomotic leakage, and a Hartmann procedure was carried out subsequently in this patient. The symptoms of pain during defecation, pelvic pain, dyspareunia, dysmenorrhea, and hematochezia showed clear improvement one year after the operation and at the time of the questionnaire. CONCLUSION: Laparoscopic low anterior resection for deeply infiltrative endometriosis is technically demanding but feasible and safe, and it improves the clinical symptoms of endometriosis in the bowel. PMID- 26258140 TI - Endoscopic Management of Foreign Bodies in the Upper Gastrointestinal Tract of Adults. AB - BACKGROUND: Foreign object ingestion and food bolus impaction are a common clinical problem. We report our clinical experiences in endoscopic management for adults, foreign body ingestion, and food bolus impaction. METHOD: A retrospective chart review study was conducted on adult patients with foreign body ingestion and food bolus impaction between January 2011 and November 2014. Patients with incomplete medical records were excluded. RESULTS: A total of 198 patients (226 incidents) were included in the study (male/female: 1.54/1; age 57 +/- 16 years). Among them, 168 foreign bodies were found successfully (74.3%). 75.6% of the foreign bodies were located in the esophagus. Food bolus impaction was most common (41.6%). 93.5% of foreign bodies in current study cohort were successfully extracted and 5 patients required surgical interventions. Comparisons between symptomatic and asymptomatic patients revealed that locations of foreign bodies in the pharynx and esophagus were the significant relevant factors (P < 0.001). Shorter time taken to initiate endoscopic interventions increased detection rate (289.75 +/- 465.94 versus 471.06 +/- 659.93 minutes, P = 0.028). CONCLUSION: Endoscopic management is a safe and highly effective procedure in extracting foreign body ingestion and food bolus impaction. Prompt endoscopic interventions can increase the chance of successful foreign bodies' detection. PMID- 26258143 TI - Engineering Micromechanical Systems for the Next Generation Wireless Capsule Endoscopy. AB - Wireless capsule endoscopy (WCE) enables the detection and diagnosis of inflammatory bowel diseases such as Crohn's disease and ulcerative colitis. However treatment of these pathologies can only be achieved through conventional means. This paper describes the next generation WCE with increased functionality to enable targeted drug delivery in the small intestinal tract. A prototype microrobot fabricated in Nylon 6 is presented which is capable of resisting peristaltic pressure through the deployment of an integrated holding mechanism and delivering targeted therapy. The holding action is achieved by extending an "anchor" spanning a 60.4 mm circumference, for an 11.0 mm diameter WCE. This function is achieved by a mechanism that occupies only 347.0 mm(3) volume, including mechanics and actuator. A micropositioning mechanism is described which utilises a single micromotor to radially position and then deploy a needle 1.5 mm outside the microrobot's body to deliver a 1 mL dose of medication to a targeted site. An analysis of the mechanics required to drive the holding mechanism is presented and an overview of microactuators and the state of the art in WCE is discussed. It is envisaged that this novel functionality will empower the next generation of WCE to help diagnose and treat pathologies of the GI tract. PMID- 26258141 TI - Using Sibling Designs to Understand Neurodevelopmental Disorders: From Genes and Environments to Prevention Programming. AB - Neurodevelopmental disorders represent a broad class of childhood neurological conditions that have a significant bearing on the wellbeing of children, families, and communities. In this review, we draw on evidence from two common and widely studied neurodevelopmental disorders-autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD)-to demonstrate the utility of genetically informed sibling designs in uncovering the nature and pathogenesis of these conditions. Specifically, we examine how twin, recurrence risk, and infant prospective tracking studies have contributed to our understanding of genetic and environmental liabilities towards neurodevelopmental morbidity through their impact on neurocognitive processes and structural/functional neuroanatomy. It is suggested that the siblings of children with ASD and ADHD are at risk not only of clinically elevated problems in these areas, but also of subthreshold symptoms and/or subtle impairments in various neurocognitive skills and other domains of psychosocial health. Finally, we close with a discussion on the practical relevance of sibling designs and how these might be used in the service of early screening, prevention, and intervention efforts that aim to alleviate the negative downstream consequences associated with disorders of neurodevelopment. PMID- 26258144 TI - Laryngeal Neuroendocrine Carcinomas: A Retrospective Study of 14 Cases. AB - Laryngeal neuroendocrine carcinomas (LNECs) are rare and highly heterogeneous which present a wide spectrum of pathological and clinical manifestations. Fourteen patients with histologically demonstrated LNEC were collected and analyzed retrospectively. The 14 cases were classified into 3 subtypes: typical carcinoid in 2, atypical carcinoid in 5, and small cell neuroendocrine carcinoma in 7. The mean survival time of the 14 patients in this study was 112.5 months (95% CI, 81.5-143.6). Surgeries were performed for 2 patients of typical carcinoid, and they were alive with no evidence of recurrence after 24 and 47 months of follow-ups. Patients in the atypical carcinoid group were treated with surgeries and postoperative radiotherapy. After 58.4 months of follow-ups (range: 9-144), 2 patients showed no evidence of disease and 1 was lost to follow-up after 72 months. The other 2 patients died of other unrelated diseases. In the small cell neuroendocrine carcinoma group, a combination of chemotherapy and radiotherapy was applied. The mean survival time was 79.7 months (95% CI, 37.9 121.4), and the 5-year survival rate was 53.6%. In conclusion, the clinical behaviors, treatment protocols, and prognosis are different for each subtype of LNECs. PMID- 26258142 TI - Noncoding RNAs, Emerging Regulators of Skeletal Muscle Development and Diseases. AB - A healthy and independent life requires skeletal muscles to maintain optimal function throughout the lifespan, which is in turn dependent on efficient activation of processes that regulate muscle development, homeostasis, and metabolism. Thus, identifying mechanisms that modulate these processes is of crucial priority. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), have emerged as a class of previously unrecognized transcripts whose importance in a wide range of biological processes and human disease is only starting to be appreciated. In this review, we summarize the roles of recently identified miRNAs and lncRNAs during skeletal muscle development and pathophysiology. We also discuss several molecular mechanisms of these noncoding RNAs. Undoubtedly, further systematic understanding of these noncoding RNAs' functions and mechanisms will not only greatly expand our knowledge of basic skeletal muscle biology, but also significantly facilitate the development of therapies for various muscle diseases, such as muscular dystrophies, cachexia, and sarcopenia. PMID- 26258145 TI - Effective Dose of Ramosetron for Prophylaxis of Postoperative Nausea and Vomiting in High-Risk Patients. AB - BACKGROUND: Postoperative nausea and vomiting (PONV) are common adverse events with an incidence of up to 80% in high-risk patients. Ramosetron, a selective 5 HT3 receptor antagonist, is widely used to prevent PONV. The purpose of this study was to evaluate the effective dose of ramosetron for the prevention of PONV in high-risk patients. METHODS: Fifty-one patients were randomly allocated to 3 groups and were administered ramosetron 0.3 mg (group A), 0.45 mg (group B), or 0.6 mg (group C), at the end of their surgery. The episodes of PONV were assessed 1, 6, 24, and 48 hours after the injection and all the adverse events were observed. RESULTS: The complete response rate in the postoperative period 6-24 hours after the anesthesia was higher in group C than in group A: 93% versus 44%. Group C's experience score of Rhodes index was lower than group A's: 0.81 +/- 2.56 versus 3.94 +/- 5.25. No adverse drug reaction could be observed in all groups. CONCLUSIONS: The effective dose of ramosetron to be injected for the near complete prophylaxis of PONV 6 to 24 hours after surgery in high-risk patients is a 0.6 mg bolus injection at the end of the surgery. PMID- 26258146 TI - Hypoglycemic Activity through a Novel Combination of Fruiting Body and Mycelia of Cordyceps militaris in High-Fat Diet-Induced Type 2 Diabetes Mellitus Mice. AB - Diabetes mellitus (DM) is currently ranked among leading causes of death worldwide in which type 2 DM is reaching an epidemic proportion. Hypoglycemic medications for type 2 DM have either proven inadequate or posed adverse effects; therefore, the Chinese herbal products are under investigation as an alternative treatment. In this study, a novel combination of fruiting body and mycelia powder of herbal Cordyceps militaris number 1 (CmNo1) was administered to evaluate their potential hypoglycemic effects in high-fat diet- (HFD-) induced type 2 DM in C57BL/6J mice. Body weight, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), and blood biochemistry indexes were measured. Results indicated that CmNo1 lowered the blood glucose level by increasing insulin sensitivity, while no change in body weight was observed. Increased protein expression of IRS-1, pIRS 1, AKT, pAKT, and GLUT-4 in skeletal muscle and adipose tissue was found indicating restoration of insulin signaling. Additionally, PPAR-gamma expression in adipose tissue restored the triglyceride and cholesterol levels. Finally, our results suggest that CmNo1 possesses strong hypoglycemic, anticholesterolemic, and antihypertriglyceridemic actions and is more economical alternate for DM treatment. PMID- 26258147 TI - Effect of Cinnamon Tea on Postprandial Glucose Concentration. AB - Glycaemic control, in particular at postprandial period, has a key role in prevention of different diseases, including diabetes and cardiovascular events. Previous studies suggest that postprandial high blood glucose levels (BGL) can lead to an oxidative stress status, which is associated with metabolic alterations. Cinnamon powder has demonstrated a beneficial effect on postprandial glucose homeostasis in animals and human models. The purpose of this study is to investigate the effect of cinnamon tea (C. burmannii) on postprandial capillary blood glucose level on nondiabetic adults. Participants were given oral glucose tolerance test either with or without cinnamon tea in a randomized clinical trial. The data revealed that cinnamon tea administration slightly decreased postprandial BGL. Cinnamon tea ingestion also results in a significantly lower postprandial maximum glucose concentration and variation of maximum glucose concentration (p < 0.05). Chemical analysis showed that cinnamon tea has a high antioxidant capacity, which may be due to its polyphenol content. The present study provides evidence that cinnamon tea, obtained from C. burmannii, could be beneficial for controlling glucose metabolism in nondiabetic adults during postprandial period. PMID- 26258148 TI - Infusion of Sulfosuccinimidyl-4-[N-maleimidomethyl]cyclohexane-1-carboxylate Conjugated MOG35-55-Coupled Spleen Cells Effectively Prevents and Reverses Experimental Autoimmune Encephalomyelitis in Mice. AB - In this study, we have evaluated our recently developed method for antigen-cell coupling using sulfosuccinimidyl-4-[N-maleimidomethyl]cyclohexane-1-carboxylate (sulfo-SMCC) heterobifunctional crosslinker in prevention and reversal of experimental autoimmune encephalomyelitis (EAE). We demonstrate that infusion of MOG35-55-coupled spleen cells (MOG-SP) significantly prevents and reverses EAE. Further studies show that the protected animals exhibit significantly delayed EAE upon EAE reinduction. Moreover, adoptive transfer of CD4+ T cells from the protected mice to naive syngeneic mice renders the recipient mice resistant to EAE induction. Unexpectedly, CD4+ T cell proliferation is similar upon ex vivo stimulation by MOG35-55 amongst all groups. However, further analysis of those proliferating CD4+ T cells shows remarkable differences in Foxp3+ regulatory T cells (70% in MOG-SP groups versus 10-25% in control groups) and in IL-17+ cells (2-3% in MOG-SP groups versus 6-9% in control groups). In addition, we discover that MOG-SP treatment also significantly attenuates MOG35-55-responding IFN-gamma producing Th1 cells. These findings suggest that MOG-SP treatment induces EAE protective MOG35-55-specific regulatory T cells and suppresses EAE pathogenic Th17 and Th1 cells. Our study provides a novel approach for antigen-based EAE immunotherapy, which can potentially be translated into clinical application for immunotherapy of multiple sclerosis. PMID- 26258149 TI - Safety and Efficacy Endpoints for Mesenchymal Stromal Cell Therapy in Renal Transplant Recipients. AB - Despite excellent short-term graft survival after renal transplantation, the long term graft outcome remains compromised. It has become evident that a combination of sustained alloreactivity and calcineurin-inhibitor- (CNI-) related nephrotoxicity results in fibrosis and consequently dysfunction of the graft. New immunosuppressive regimens that can minimize or eliminate side effects, while maintaining efficacy, are required to improve long-term graft survival. In this perspective mesenchymal stromal cells (MSCs) are an interesting candidate, since MSCs have immunosuppressive and regenerative properties. The first clinical trials with MSCs in renal transplantation showed safety and feasibility and displayed promising results. Recently, the first phase II studies have been started. One of the most difficult and challenging aspects in those early phase trials is to define accurate endpoints that can measure safety and efficacy of MSC treatment. Since both graft losses and acute rejection rates declined, alternative surrogate markers such as renal function, histological findings, and immunological markers are used to measure efficacy and to provide mechanistic insight. In this review, we will discuss the current status of MSCs in renal transplantation with a focus on the endpoints used in the different experimental and clinical studies. PMID- 26258150 TI - Sepsis: From Pathophysiology to Individualized Patient Care. AB - Sepsis has become a major health economic issue, with more patients dying in hospitals due to sepsis related complications compared to breast and colorectal cancer together. Despite extensive research in order to improve outcome in sepsis over the last few decades, results of large multicenter studies were by-and-large very disappointing. This fiasco can be explained by several factors, but one of the most important reasons is the uncertain definition of sepsis resulting in very heterogeneous patient populations, and the lack of understanding of pathophysiology, which is mainly based on the imbalance in the host-immune response. However, this heroic research work has not been in vain. Putting the results of positive and negative studies into context, we can now approach sepsis in a different concept, which may lead us to new perspectives in diagnostics and treatment. While decision making based on conventional sepsis definitions can inevitably lead to false judgment due to the heterogeneity of patients, new concepts based on currently gained knowledge in immunology may help to tailor assessment and treatment of these patients to their actual needs. Summarizing where we stand at present and what the future may hold are the purpose of this review. PMID- 26258151 TI - Mesenchymal Stromal Cell Therapy in Ischemia/Reperfusion Injury. AB - Ischemia/reperfusion injury (IRI) represents a worldwide public health issue of increasing incidence. IRI may virtually affect all organs and tissues and is associated with significant morbidity and mortality. Particularly, the duration of blood supply deprivation has been recognized as a critical factor in stroke, hemorrhagic shock, or myocardial infarction, as well as in solid organ transplantation (SOT). Pathophysiologically, IRI causes multiple cellular and tissular metabolic and architectural changes. Furthermore, the reperfusion of ischemic tissues induces both local and systemic inflammation. In the particular field of SOT, IRI is an unavoidable event, which conditions both short- and long term outcomes of graft function and survival. Clinically, the treatment of patients with IRI mostly relies on supportive maneuvers since no specific target oriented therapy has been validated thus far. In the present review, we summarize the current literature on mesenchymal stromal cells (MSC) and their potential use as cell therapy in IRI. MSC have demonstrated immunomodulatory, anti inflammatory, and tissue repair properties in rodent studies and in preliminary clinical trials, which may open novel avenues in the management of IRI and SOT. PMID- 26258153 TI - Managing Opioid Use Disorder During and After Acute Hospitalization: A Case-Based Review Clarifying Methadone Regulation for Acute Care Settings. AB - OBJECTIVE: Treatment with an opioid agonist such as methadone or buprenorphine is the standard of care for opioid use disorder. Persons with opioid use disorder are frequently hospitalized, and may be undertreated due to provider misinformation regarding the legality of prescribing methadone for inpatients. Using a case-based review, this article aims to describe effective management of active opioid withdrawal and ongoing opioid use disorder using methadone or buprenorphine among acutely ill, hospitalized patients. METHODS: We reviewed pertinent medical and legal literature and consulted with national legal experts regarding methadone for opioid withdrawal and opioid maintenance therapy in hospitalized, general medical and surgical patients, and describe a real-life example of successful implementation of inpatient methadone for these purposes. RESULTS: Patients with opioid use disorders can be effectively and legally initiated on methadone maintenance therapy or buprenorphine during an inpatient hospitalization by clinical providers and successfully transitioned to an outpatient methadone maintenance or buprenorphine clinic after discharge for ongoing treatment. CONCLUSIONS: Inpatient methadone or buprenorphine prescribing is safe and evidence-based, and can be used to effectively treat opioid withdrawal and also serves as a bridge to outpatient treatment of opioid use disorders. PMID- 26258152 TI - Innate Immune Defenses in Human Tuberculosis: An Overview of the Interactions between Mycobacterium tuberculosis and Innate Immune Cells. AB - Tuberculosis (TB) remains a serious global public health problem that results in up to 2 million deaths each year. TB is caused by the human pathogen, Mycobacterium tuberculosis (Mtb), which infects primarily innate immune cells patrolling the lung. Innate immune cells serve as barometers of the immune response against Mtb infection by determining the inflammatory milieu in the lungs and promoting the generation of adaptive immune responses. However, innate immune cells are also potential niches for bacterial replication and are readily manipulated by Mtb. Our understanding of the early interactions between Mtb and innate immune cells is limited, especially in the context of human infection. This review will focus on Mtb interactions with human macrophages, dendritic cells, neutrophils, and NK cells and detail evidence that Mtb modulation of these cells negatively impacts Mtb-specific immune responses. Furthermore, this review will emphasize important innate immune pathways uncovered through human immunogenetic studies. Insights into the human innate immune response to Mtb infection are necessary for providing a rational basis for the augmentation of immune responses against Mtb infection, especially with respect to the generation of effective anti-TB immunotherapeutics and vaccines. PMID- 26258154 TI - Genitourinary Procedures as Risk Factors for Prosthetic Hip or Knee Infection: A Hospital-Based Prospective Case-Control Study. AB - Background. The purpose of this study was to determine the risk of prosthetic joint infection (PJI) as a complication of routine genitourinary (GU) procedures in patients with total hip arthroplasty (THA) or total knee arthroplasty (TKA) and to study the impact of antibiotic prophylaxis administered prior to these procedures. Methods. We conducted a prospective, single-center, case-control study between December 1, 2001 and May 31, 2006. Case patients were hospitalized with total hip or knee PJI. Control subjects underwent a THA or TKA and were hospitalized during the same period on the same orthopedic floor without a PJI. Data regarding demographic features and potential risk factors were collected. The outcome measure was the odds ratio (OR) of PJI after GU procedures performed within 2 years of admission. Results. A total of 339 case patients and 339 control subjects were enrolled in the study. Of these, 52 cases (15%) and 55 controls (16%) had undergone a GU procedure in the preceding 2 years. There was no increased risk of PJI for patients undergoing a GU procedure with or without antibiotic prophylaxis (adjusted OR [aOR] = 1.0, 95% confidence interval [CI] = 0.2-4.5, P = .95 and aOR = 1.0, 95% CI = 0.6-1.7, P = .99, respectively). Results were similar in a subset of patients with a joint age less than 6 months, less than 1 year, or greater than 1 year. Conclusions. Genitourinary procedures were not risk factors for subsequent PJI. The use of antibiotic prophylaxis before GU procedures did not decrease the risk of subsequent PJI in our study. PMID- 26258155 TI - Acute Phase Reactants in Infections: Evidence-Based Review and a Guide for Clinicians. AB - Acute-phase reactants such as erythrocyte sedimentation rate and C-reactive protein have traditionally been used as markers for inflammation and as a measure of "sickness index" in infectious and noninfectious conditions. In the last decade, more data have become available on the wider and more specific role for these markers in the management of complex infections. This includes the potential role in early diagnosis, in differentiating infectious from noninfectious causes, as a prognostic marker, and in antibiotic guidance strategies. A better defined role for biological markers as a supplement to clinical assessment may lead to more judicious antibiotic prescriptions, and it has the potential for a long-term favorable impact on antimicrobial stewardship and antibiotic resistance. Procalcitonin as a biological marker has been of particular interest in this regard. This review examines the current published evidence and summarizes the role of various acute-phase markers in infections. A MEDLINE search of English-language articles on acute-phase reactants and infections published between 1986 and March 2015 was conducted. Additional articles were also identified through a search of references from the retrieved articles, published guidelines, systematic reviews, and meta-analyses. PMID- 26258156 TI - Invasive Fusariosis in the Voriconazole Era: Single-Center 13-Year Experience. AB - Background. Invasive fusariosis remains an aggressive, albeit infrequent infection in immunocompromised patients. Methods. We identified all cases of invasive fusariosis between January 2002 and December 2014. We recorded patient characteristics including clinical presentation, treatment, and outcomes at 6 and 12 weeks after diagnosis, as well as species identification and antifungal drug susceptibilities. Results. Fifteen patients were diagnosed with proven (12, 80%) or probable (3, 20%) fusariosis. Median age was 60 years (range, 26-78), and 10 patients were male. Underlying conditions included hematological malignancies (13, 87%), juvenile idiopathic arthritis (1, 7%), and third-degree burns (1, 7%). Five patients underwent hematopoietic stem-cell transplantation before diagnosis. Six patients (40%) received systemic glucocorticoids, and 11 patients (73%) had prolonged neutropenia at the time of diagnosis. Clinical presentations included the following: skin/soft tissue infection (8, 53%), febrile neutropenia (4, 27%), respiratory tract infection (2, 13%), and septic arthritis (1, 7%). Twelve patients were treated with voriconazole: 6 (40%) with voriconazole alone, 4 (27%) with voriconazole and terbinafine, and 2 (13%) with voriconazole, terbinafine, and amphotericin. One patient (7%) was treated with terbinafine alone, and another with micafungin alone. Four patients underwent surgical debridement (4, 27%). Susceptibility testing was performed on 9 isolates; 8 demonstrated voriconazole minimum inhibitory concentrations >=4 ug/mL. The cumulative probability of survival was 66.7% and 53.3% at 6 and 12 weeks after diagnosis. Conclusions. Mortality associated with invasive fusariosis remains high. Cumulative mortality at our center was lower than previous reports despite elevated voriconazole minimum inhibitory concentrations. Combination therapy should be studied systematically for fusariosis. PMID- 26258157 TI - Impact of Late Oseltamivir Treatment on Influenza Symptoms in the Outpatient Setting: Results of a Randomized Trial. AB - We conducted a double-blind, randomized trial of 134 outpatients with polymerase chain reaction-confirmed influenza to assess the effects of oseltamivir initiated 48-119 hours after illness onset. Oseltamivir treatment did not reduce illness duration, severity, or duration of virus detection. However, the power of this study was limited due to lower than expected enrollment. PMID- 26258158 TI - Generation of Mammalian Host-adapted Leptospira interrogans by Cultivation in Peritoneal Dialysis Membrane Chamber Implantation in Rats. AB - Leptospira interrogans can infect a myriad of mammalian hosts, including humans (Bharti et al., 2003; Ko et al., 2009). Following acquisition by a suitable host, leptospires disseminate via the bloodstream to multiple tissues, including the kidneys, where they adhere to and colonize the proximal convoluted renal tubules (Athanazio et al., 2008). Infected hosts shed large number of spirochetes in their urine and the leptospires can survive in different environmental conditions before transmission to another host. Differential gene expression by Leptospira spp. permits adaption to these new conditions. Here we describe a protocol for the cultivation of Leptospira interrogans within Dialysis Membrane Chambers (DMCs) implanted into the peritoneal cavities of Sprague-Dawley rats (Caimano et al., 2014). This technique was originally developed to study mammalian adaption by the Lyme disease spirochete, Borrelia burgdorferi (Akins et al., 1998; Caimano, 2005). The small pore size (8,000 MWCO) of the dialysis membrane tubing used for this procedure permits access to host nutrients but excludes host antibodies and immune effector cells. Given the physiological and environmental similarities between DMCs and the proximal convoluted renal tubule, we reasoned that the DMC model would be suitable for studying in vivo gene expression by L. interrogans. In a 20 to 30 min procedure, DMCs containing virulent leptospires are surgically-implanted into the rat peritoneal cavity. Nine to 11 days post implantation, DMCs are explanted and organisms recovered. Typically, a single DMC yields ~109 mammalian host-adapted leptospires (Caimano et al., 2014). In addition to providing a facile system for studying the transcriptional and physiologic changes pathogenic L. interrogans undergo within the mammal, the DMC model also provides a rationale basis for selecting new targets for mutagenesis and the identification of novel virulence determinants. Caution: Leptospira interrogans is a BSL-2 level pathogen and known to be excreted in the urine of infected animals. Animals should be handled and disposed of using recommended Animal Biosafety Levels (ABSL) for infectious agents using vertebrate animal guidelines. Note: All protocols using live animals must conform to governmental regulations regarding the care and use of laboratory animals. The success of this protocol is dependent on the proper use of aseptic techniques during all stages of both dialysis membrane chamber preparation and animal surgery. PMID- 26258159 TI - Dysfunctional Reward Processing in Depression. AB - Anhedonia - diminished pleasure and/or decreased reactivity to pleasurable stimuli - is a core feature of depression that frequently persists after treatment. As a result, extensive effort has been directed towards characterizing the psychological and biological processes that mediate dysfunctional reward processing in depression. Reward processing can be parsed into sub-components that include motivation, reinforcement learning, and hedonic capacity, which, according to preclinical and neuroimaging evidence, involve partially dissociable brain systems. In line with this, recent findings indicate that behavioral impairments and neural abnormalities in depression vary across distinct reward related constructs. Ultimately, improved understanding of precise reward-related dysfunctions in depression promises to improve diagnostic and therapeutic efforts in depression. PMID- 26258160 TI - Risk perceptions and health behavior. AB - Risk perceptions - or an individual's perceived susceptibility to a threat - are a key component of many health behavior change theories. Risk perceptions are often targeted in health behavior change interventions, and recent meta-analytic evidence suggests that interventions that successfully engage and change risk perceptions produce subsequent increases in health behaviors. Here, we review recent literature on risk perceptions and health behavior, including research on the formation of risk perceptions, types of risk perceptions (including deliberative, affective, and experiential), accuracy of risk perceptions, and associations and interactions among types of risk perceptions. Taken together, existing research suggests that disease risk perceptions are a critical determinant of health behavior, although the nature of the association among risk perceptions and health behavior may depend on the profile of different types of risk perceptions and the accuracy of such perceptions. PMID- 26258161 TI - The relationship between CSF tau markers, hippocampal volume and delayed primacy performance in cognitively intact elderly individuals. AB - BACKGROUND: Primacy performance in recall has been shown to predict cognitive decline in cognitively intact elderly, and conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Delayed primacy performance, but not delayed non-primacy performance, has been shown to be associated with hippocampal volume in cognitively intact older individuals. Since presence of neurofibrillary tangles is an early sign of AD-related pathology, we set out to test whether cerebrospinal fluid (CSF) levels of tau had an effect on delayed primacy performance, while controlling for hippocampal volume and CSF Abeta 1-42 levels. METHODS: Forty-seven individuals, 60 or older and cognitively intact, underwent a multi-session study including lumbar puncture, an MRI scan of the head and memory testing. RESULTS: Our regression analyses show that CSF levels of hyperphosphorylated (P) tau are only associated with reduced delayed primacy performance when hippocampal volumes are smaller. CONCLUSION: Our findings suggest that hippocampal size may play a protective role against the negative effects of P tau on memory. PMID- 26258162 TI - Traits of patients who screen positive for dementia and refuse diagnostic assessment. AB - BACKGROUND: As part of the debate about screening for dementia, it is critical to understand why patients agree or disagree to diagnostic assessment after a positive screening test. We used the Perceptions Regarding Investigational Screening for Memory in Primary Care (PRISM-PC) questionnaire to measure the characteristics of patients who screened positive for dementia but refused further diagnostic assessment. METHODS: Survey of patients >=65 years old without a diagnosis of dementia attending primary care clinics in Indianapolis, IN, in 2008 and 2009. RESULTS: Five hundred and fifty-four individuals completed the PRISM-PC and 63 screened positive. Of those, 21 (33%) accepted and 42 (67%) refused diagnostic assessment. In adjusted models, having larger stigma domain scores and living alone were significantly associated with increased odds of refusing the diagnostic assessment. CONCLUSION: Despite screening positive, many patients refused a diagnostic assessment. Living alone and the perceived stigmas of dementia are associated with the refusal of diagnostic assessment for dementia. PMID- 26258163 TI - Antigenotoxic Effect of Trametes spp. Extracts against DNA Damage on Human Peripheral White Blood Cells. AB - Trametes species have been used for thousands of years in traditional and conventional medicine for the treatment of various types of diseases. The goal was to evaluate possible antigenotoxic effects of mycelium and basidiocarp extracts of selected Trametes species and to assess dependence on their antioxidant potential. Trametes versicolor, T. hirsuta, and T. gibbosa were the species studied. Antigenotoxic potentials of extracts were assessed on human peripheral white blood cells with basidiocarp and mycelium extracts of the species. The alkaline comet test was used for detection of DNA strand breaks and alkali-labile sites, as well as the extent of DNA migration. DPPH assay was used to estimate antioxidative properties of extracts. Fruiting body extracts of T. versicolor and T. gibbosa as well as T. hirsuta extracts, except that at 20.0 mg/mL, were not genotoxic agents. T. versicolor extract had at 5.0 mg/mL the greatest antigenotoxic effect in both pre- and posttreatment of leukocytes. The mycelium extracts of the three species had no genotoxic activity and significant antigenotoxic effect against H2O2-induced DNA damage, both in pre- and posttreatment. The results suggest that extracts of these three species could be considered as strong antigenotoxic agents able to stimulate genoprotective response of cells. PMID- 26258164 TI - Automation of Presentation Record Production Based on Rich-Media Technology Using SNT Petri Nets Theory. AB - Rich-media describes a broad range of digital interactive media that is increasingly used in the Internet and also in the support of education. Last year, a special pilot audiovisual lecture room was built as a part of the MERLINGO (MEdia-rich Repository of LearnING Objects) project solution. It contains all the elements of the modern lecture room determined for the implementation of presentation recordings based on the rich-media technologies and their publication online or on-demand featuring the access of all its elements in the automated mode including automatic editing. Property-preserving Petri net process algebras (PPPA) were designed for the specification and verification of the Petri net processes. PPPA does not need to verify the composition of the Petri net processes because all their algebraic operators preserve the specified set of the properties. These original PPPA are significantly generalized for the newly introduced class of the SNT Petri process and agent nets in this paper. The PLACE-SUBST and ASYNC-PROC algebraic operators are defined for this class of Petri nets and their chosen properties are proved. The SNT Petri process and agent nets theory were significantly applied at the design, verification, and implementation of the programming system ensuring the pilot audiovisual lecture room functionality. PMID- 26258165 TI - An Adaptive Multilevel Security Framework for the Data Stored in Cloud Environment. AB - Cloud computing is renowned for delivering information technology services based on internet. Nowadays, organizations are interested in moving their massive data and computations into cloud to reap their significant benefits of on demand service, resource pooling, and rapid elasticity that helps to satisfy the dynamically changing infrastructure demand without the burden of owning, managing, and maintaining it. Since the data needs to be secured throughout its life cycle, security of the data in cloud is a major challenge to be concentrated on because the data is in third party's premises. Any uniform simple or high level security method for all the data either compromises the sensitive data or proves to be too costly with increased overhead. Any common multiple method for all data becomes vulnerable when the common security pattern is identified at the event of successful attack on any information and also encourages more attacks on all other data. This paper suggests an adaptive multilevel security framework based on cryptography techniques that provide adequate security for the classified data stored in cloud. The proposed security system acclimates well for cloud environment and is also customizable and more reliant to meet the required level of security of data with different sensitivity that changes with business needs and commercial conditions. PMID- 26258166 TI - Attitudes and Health Behavior of Lawyers in Coimbatore, Tamil Nadu. AB - The aim of the study is to evaluate the differences in the behavior and attitudes of male and female lawyers regarding their lifestyles and health habits. Lawyers were randomly chosen. Data was obtained through a structured questionnaire distributed among the lawyers of Coimbatore district, Tamil Nadu. Lawyers are found to have unfavorable health practices related to use of tobacco and alcohol, exercise, diet, sleeping habits, and stress. This resulted in obesity, depression, and blood pressure. Many lawyers reported use of alcohol regularly, even as often as every day, and nearly half of them smoked. Many of the lawyers had poor feeding habit of skipping meals and eating snacks as breakfast. Most lawyers considered stressful situations to be unavoidable. Thus identifying individual lawyers with poor health behaviors and providing medical help are essential. PMID- 26258168 TI - Corrigendum to "Extended Spectrum Beta-Lactamase Carriage State among Elderly Nursing Home Residents in Beirut". PMID- 26258167 TI - Assessment of Population Exposure to Coarse and Fine Particulate Matter in the Urban Areas of Chennai, India. AB - Research outcomes from the epidemiological studies have found that the course (PM10) and the fine particulate matter (PM2.5) are mainly responsible for various respiratory health effects for humans. The population-weighted exposure assessment is used as a vital decision-making tool to analyze the vulnerable areas where the population is exposed to critical concentrations of pollutants. Systemic sampling was carried out at strategic locations of Chennai to estimate the various concentration levels of particulate pollution during November 2013 January 2014. The concentration of the pollutants was classified based on the World Health Organization interim target (IT) guidelines. Using geospatial information systems the pollution and the high-resolution population data were interpolated to study the extent of the pollutants at the urban scale. The results show that approximately 28% of the population resides in vulnerable locations where the coarse particulate matter exceeds the prescribed standards. Alarmingly, the results of the analysis of fine particulates show that about 94% of the inhabitants live in critical areas where the concentration of the fine particulates exceeds the IT guidelines. Results based on human exposure analysis show the vulnerability is more towards the zones which are surrounded by prominent sources of pollution. PMID- 26258170 TI - Theory and Application on Rough Set, Fuzzy Logic, and Granular Computing. PMID- 26258169 TI - Adsorption Removal of Environmental Hormones of Dimethyl Phthalate Using Novel Magnetic Adsorbent. AB - Magnetic polyvinyl alcohol adsorbent M-PVAL was employed to remove and concentrate dimethyl phthalate DMP. The M-PVAL was prepared after sequential syntheses of magnetic Fe3O4 (M) and polyvinyl acetate (M-PVAC). The saturated magnetizations of M, M-PVAC, and M-PVAL are 57.2, 26.0, and 43.2 emu g(-1) with superparamagnetism, respectively. The average size of M-PVAL by number is 0.75 MUm in micro size. Adsorption experiments include three cases: (1) adjustment of initial pH (pH0) of solution to 5, (2) no adjustment of pH0 with value in 6.04 6.64, and (3) adjusted pH0 = 7. The corresponding saturated amounts of adsorption of unimolecular layer of Langmuir isotherm are 4.01, 5.21, and 4.22 mg g(-1), respectively. Values of heterogeneity factor of Freundlich isotherm are 2.59, 2.19, and 2.59 which are greater than 1, revealing the favorable adsorption of DMP/M-PVAL system. Values of adsorption activation energy per mole of Dubinin Radushkevich isotherm are, respectively, of low values of 7.04, 6.48, and 7.19 kJ mol(-1), indicating the natural occurring of the adsorption process studied. The tiny size of adsorbent makes the adsorption take place easily while its superparamagnetism is beneficial for the separation and recovery of micro adsorbent from liquid by applying magnetic field after completion of adsorption. PMID- 26258171 TI - Automated Detection of 3D Landmarks for the Elimination of Non-Biological Variation in Geometric Morphometric Analyses. AB - Landmark-based morphometric analyses are used by anthropologists, developmental and evolutionary biologists to understand shape and size differences (eg. in the cranioskeleton) between groups of specimens. The standard, labor intensive approach is for researchers to manually place landmarks on 3D image datasets. As landmark recognition is subject to inaccuracies of human perception, digitization of landmark coordinates is typically repeated (often by more than one person) and the mean coordinates are used. In an attempt to improve efficiency and reproducibility between researchers, we have developed an algorithm to locate landmarks on CT mouse hemi-mandible data. The method is evaluated on 3D meshes of 28-day old mice, and results compared to landmarks manually identified by experts. Quantitative shape comparison between two inbred mouse strains demonstrate that data obtained using our algorithm also has enhanced statistical power when compared to data obtained by manual landmarking. PMID- 26258172 TI - Oxa, Thia, Heterocycle, and Carborane Analogues of SQ109: Bacterial and Protozoal Cell Growth Inhibitors. AB - We synthesized a library of 48 analogs of the Mycobacterium tuberculosis cell growth inhibitor SQ109 in which the ethylene diamine linker was replaced by oxa-, thia- or heterocyclic species, and in some cases, the adamantyl group was replaced by a 1,2-carborane or the N-geranyl group by another hydrophobic species. Compounds were tested against Mycobacterium tuberculosis (H37Rv and/or Erdman), Mycobacterium smegmatis, Bacillus subtilis, Escherichia coli, Saccharomyces cerevisiae, Trypanosoma brucei and two human cell lines (human embryonic kidney, HEK293T, and the hepatocellular carcinoma, HepG2). Most potent activity was found against T. brucei, the causative agent of human African trypanosomiasis, and involved targeting of the mitochondrial membrane potential with 15 SQ109 analogs being more active than was SQ109 in cell growth inhibition, having IC50 values as low as 12 nM (5.5 ng/mL) and a selectivity index of ~300. PMID- 26258173 TI - Biosynthesis of Squalene from Farnesyl Diphosphate in Bacteria: Three Steps Catalyzed by Three Enzymes. AB - Squalene (SQ) is an intermediate in the biosynthesis of sterols in eukaryotes and a few bacteria and of hopanoids in bacteria where they promote membrane stability and the formation of lipid rafts in their hosts. The genes for hopanoid biosynthesis are typically located on clusters that consist of four highly conserved genes-hpnC, hpnD, hpnE, and hpnF-for conversion of farnesyl diphosphate (FPP) to hopene or related pentacyclic metabolites. While hpnF is known to encode a squalene cyclase, the functions for hpnC, hpnD, and hpnE are not rigorously established. The hpnC, hpnD, and hpnE genes from Zymomonas mobilis and Rhodopseudomonas palustris were cloned into Escherichia coli, a bacterium that does not contain genes homologous to hpnC, hpnD, and hpnE, and their functions were established in vitro and in vivo. HpnD catalyzes formation of presqualene diphosphate (PSPP) from two molecules of FPP; HpnC converts PSPP to hydroxysqualene (HSQ); and HpnE, a member of the amine oxidoreductase family, reduces HSQ to SQ. Collectively the reactions catalyzed by these three enzymes constitute a new pathway for biosynthesis of SQ in bacteria. PMID- 26258174 TI - Catheter Ablation for Atrial Fibrillation in Heart Failure Patients: A Meta Analysis of Randomized Controlled Trials. AB - BACKGROUND: Rhythm control with antiarrhythmic drugs (AADs) is not superior to rate control in patients with heart failure (HF) and atrial fibrillation (AF), but AF ablation may be more successful at achieving rhythm control than AADs. However, risks for both ablation and AADs are likely higher and success rates lower in patients with HF. OBJECTIVE: To compare rate control versus AF catheter ablation strategies in patients with AF and HF. METHODS: We conducted a meta analysis of trials which randomized HF patients (LVEF<50%) with AF to a rate control or AF catheter ablation strategy and reported change in LVEF, quality of life, 6-minute walk test, or peak oxygen consumption. Study quality and heterogenity were assessed using Jadad scores and Cochran's Q statistics, respectively. Mantel Haenszel relative risks and mean differences were calculated using random effect models. RESULTS: Four trials (N=224) met inclusion criteria; 82.5% (n=185) had persistent AF. AF ablation was associated with an increase in LVEF (mean difference 8.5%; 95%CI 6.4,10.7%; P<0.001) compared to rate control. AF ablation was superior in improving quality of life by Minnesota Living with Heart Failure (MLWHF) questionnaire scores (mean difference -11.9; 95%CI -17.1, 6.6; P<0.001). Peak oxygen consumption and 6-minute walk distance increased in AF ablation compared to rate control patients (mean difference 3.2; 95%CI 1.1,5.2; P=0.003; mean difference 34.8; 95%CI 2.9, 66.7; P = 0.03, respectively). In the persistent AF subgroup LVEF and MLWHF were significantly improved with AF ablation. Major adverse event rates (RR 1.3; 95% CI, 0.4, 3.9; p=0.64) were not significantly different. No significant heterogeneity was evident. CONCLUSIONS: In patients with HF and AF, AF catheter ablation is superior to rate control in improving LVEF, quality of life and functional capacity. Prior to accepting a rate control strategy in HF patients with persistent or drug refractory AF, consideration should be given to AF ablation. PMID- 26258175 TI - Interfacial Adaptation of Composite Restorations Before and After Light Curing: Effects of Adhesive and Filling Technique. AB - PURPOSE: To investigate the effects of placement technique and adhesive material on adaptation of composites before and after light curing. MATERIALS AND METHODS: Cylindrical cavities (3 mm diameter, 1.7 mm depth) in extracted human molars were restored in 6 groups (n=5) using 2 adhesives--two-step self-etching Clearfil SE Bond 2 (SE2) and all-in-one Clearfil Tri-S Bond Plus (TSP) (Kuraray Noritake Dental)--and 2 composites--Estelite Sigma Quick (ESQ) and Estelite Flow Quick (FLQ) (Tokuyama Dental)--placed with three different techniques: ESQ bulk placed, FLQ lining followed by ESQ and FLQ bulk placed. Specimens were scanned twice using swept-source optical coherence tomography (SS-OCT) before and after photopolymerization of the composite. Gap formation during polymerization or the difference in floor interface (DFI%) and final unsealed interface (USI%) were measured by image coregistration and subtraction on 6 diametrical planes across each scan. RESULTS: Two-way ANOVA suggested that both factors (adhesive and filling technique) and their interaction were significant (p<0.001). SE2 showed significantly lower DFI% than did TSP when the composites were placed in bulk, but no difference was found when flowable lining was applied (p<0.05). Within TSP, all filling techniques were significantly different and the lining group showed the lowest values, followed by ESQ-bulk. Overall, SE2 always showed lower UFI% than did TSP, while there was no difference among different techniques within SE2. CONCLUSION: SS-OCT is a unique method to observe the pre-existing interfacial defects and gaps developed during polymerization, which were found to depend on both placement technique and applied adhesive. PMID- 26258176 TI - Effect of Fluoride-containing Restorative Materials on Dentin Adhesion and Demineralization of Hard Tissues Adjacent to Restorations. AB - PURPOSE: This study evaluated (1) the dentin bond strength of fluoridated restorative systems following aging and (2) the enamel/dentin microhardness around restorations after a pH-cycling regimen. MATERIALS AND METHODS: Sixty-four human third molars and four restorative systems were used. A resin-modified glass ionomer (GC Fuji II LC) was used as a fluoride-containing material in the positive control group, while Adper Easy Bond adhesive and Filtek Z350 XT composite resin, which are not fluoridated, were used together in the negative control group. Beautifil II composite resin and FL-Bond II adhesive, both fluoride-containing materials, were compared to Bond Force and Estelite Sigma Quick restorative system, which only contain fluoride in the adhesive. For dentin bond strengths, specimens of each material were fabricated for two test groups (n=8): group 1: tested after 24 h; group 2: tested after 1 year of storage in artificial saliva. Both groups were tested using a microtensile method. For the cross-sectional microhardness test, standardized Class V cavities were prepared and filled with the different restorative systems. After experiencing repeated thermocycling and being subjected to pH-cycling, the teeth were sectioned. The microhardness was measured in enamel and dentin at 50 MUm from the cavity wall and at six depths in relation to the surface subjected to pH cycling. RESULTS: None of the restorative systems showed decreased bond strength after storage for one year in artificial saliva. No significant differences in microhardness were observed among the restorative materials on enamel and dentin. CONCLUSION: All the restorative systems evaluated presented stable bond strength after one year of storage. The pH cycling caused a reduction in the superficial enamel microhardness close to the cavity wall. In dentin, the demineralization affected the superficial and sub-surface areas. PMID- 26258177 TI - Six-month Clinical Evaluation of a Self-adhesive Flowable Composite in Noncarious Cervical Lesions. AB - PURPOSE: The aim of this randomized, controlled, single-center, split-mouth clinical trial was to evaluate the clinical performance of a self-adhesive flowable composite resin (SAFC) in noncarious cervical lesions in comparison with a nanohybrid composite applied with a three-step etch-and-rinse adhesive system (E&Ra/nanoC). MATERIALS AND METHODS: Eighty noncarious cervical lesions were included and assigned to one of two groups according to the split-mouth design. The cervical lesions in the experimental group were restored with an SAFC (Fusio Liquid Dentin), while a nanohybrid composite (G-aenial) applied with a three-step etch-and-rinse adhesive system (Optibond FL) was used for the control group. Clinical evaluation was performed after 1 week and again at 6 months according to FDI criteria. Data were analyzed using Wilcoxon Signed Rank and Mann-Whitney U tests (alpha=0.05). RESULTS: After 6 months, 27 of the 40 SAFC restorations were in clinically unacceptable condition due to retention failure; this corresponded to a success rate of 33% compared to the success rate of 100% for the E&Ra/ nanoC restorations (p<0.05). For other criteria examined, the difference between the two groups was only statistically significant for color and translucency (p<0.05). CONCLUSION: The clinical performance of the SAFC was found to be unacceptable after 6 months of clinical use. PMID- 26258178 TI - Effect of Thickness, Processing Technique and Cooling Rate Protocol on the MUTBS of a Bilayer Ceramic System. AB - PURPOSE: To evaluate the influence of different processing techniques, ceramic thicknesses, and cooling rate protocols on the MUTBS of a veneering ceramic to zirconia (Y-TZP). MATERIALS AND METHODS: Eighty Y-TZP ceramic blocks (VITA In Ceram 2000) with dimensions of 10 x 7 x 5 mm were obtained. The blocks were sintered in a special furnace at 1500 degrees for 2 h, wet ground, and divided into 8 groups according to the factors "processing technique" (P: pressed/veneering ceramic PM9; or V: layered/ veneering ceramic VM9), "thickness" (2 mm and 4 mm), and "cooling protocol" (S: slow [10 degrees C/s]; F: fast [50 degrees C/s]). The Y-TZP/veneering ceramic blocks were sectioned to produce non trimmed bar specimens (bonded area: 1+/-0.1 mm2), which were submitted to 1200 thermal cycles (5 degrees C and 55 degrees C, 30-s dwell time) and stored for 1 week in distilled water (37 degrees C) before microtensile testing in a universal test machine (EMIC, 1 mm/min). The data in MPa were analyzed statistically using three-way ANOVA and Tukey's test. RESULTS: ANOVA revealed that only the factor processing technique was significant (p=0.015), unlike the factors thickness (p=0.111) and cooling protocol (p=0.202). The majority of the failures were classified as adhesive. CONCLUSION: Layered application of a thin veneering ceramic using a fast cooling rate resulted in improved bonding between veneering ceramic and zirconia. PMID- 26258179 TI - Fishing the PTM proteome with chemical approaches using functional solid phases. AB - Post-translational modifications (PTMs) are covalent additions of functional groups to proteins and are known to play essential roles in biological processes. Covalently attached PTMs are usually present at substoichiometric levels, implying that a PTM proteome is often present in only a small fraction of the entire proteome. The low abundance of PTMs creates a tremendous analytical challenge for PTM proteomics. New analytical strategies, especially enrichment approaches, are required to allow the comprehensive determination of PTMs. Solid phase capture of PTMs through chemical reactions provides the most specific approach for fishing the PTM proteome, and based on these chemical reactions, a variety of novel functional nanomaterials have been developed. This review mainly focuses on the currently available chemical approaches for investigating PTMs, as well as the functional solid phases used for PTM proteome separation. PMID- 26258180 TI - Electrochemical immunosensor for sensitive determination of the anorexigen peptide YY at grafted reduced graphene oxide electrode platforms. AB - The first electrochemical immunosensor for the determination of peptide YY is reported in this paper. A novel electrochemical platform, prepared by the electrochemical grafting of the diazonium salt of 4-aminobenzoic acid onto a reduced graphene oxide-modified glassy carbon electrode, was used, on which the covalent immobilization of specific anti-PYY antibodies was accomplished. The HOOC-Phe-rGO/GCEs were characterized using cyclic voltammetry and electrochemical impedance spectroscopy. The different variables affecting the preparation of the modified electrodes and the performance of the immunosensor were optimized. Under the optimized conditions, a calibration plot for PYY showing a linear range extending between 10(-4) and 10(2) ng mL(-1) was found. This range is adequate for the determination of this protein in real samples, since the expected concentration in human serum is around 100 pg mL(-1). The limit of detection was 0.01 pg mL(-1) of PYY. The immunosensor exhibited good reproducibility of the PYY measurements, excellent storage stability and selectivity, as well as a shorter assay time than those of ELISA kits. The usefulness of the immunosensor for the analysis of real samples was demonstrated by analyzing human serum samples spiked with PYY at three concentration levels. PMID- 26258181 TI - A 3D printed microliquid jet with an adjustable nozzle diameter. AB - Microliquid jets have many applications, in particular in the fields of spectroscopy/analysis of samples susceptible to beam damage. Herein, we report a microliquid jet, manufactured with 3D printing technology, with a tuneable nozzle diameter output. This strategy increases the breadth of techniques that can be covered with a single microliquid jet. PMID- 26258182 TI - Colorimetric detection of sequence-specific microRNA based on duplex-specific nuclease-assisted nanoparticle amplification. AB - Developing simple and rapid methods for sequence-specific microRNA (miRNA) analysis is imperative to the miRNA study and use in clinical diagnosis. We have developed a colorimetric method for miRNA detection based on duplex-specific nuclease (DSN)-assisted signal amplification coupled to the aggregation of gold nanoparticles (AuNPs). The proposed method involves two processes: target mediated probe digestion by a DSN enzyme and probe-triggered AuNP aggregation as a switch for signal output. The reaction system consists of a rationally designed probe complex formed by two partly complementary DNA probes, and two sets of different oligonucleotide-modified AuNPs with sequences complementary to a DNA probe in the probe complex. In the presence of target miRNA, the probe complex is invaded, resulting in the formation of a miRNA-probe heteroduplex as the substrate of the DSN enzyme, and releasing the other probe to link to the AuNPs. The proposed method allows quantitative detection of miR-122 in the range of 20 pM to 1 nM with a detection limit of ~16 pM, and shows an excellent ability to discriminate single-base differences. Moreover, the detection assay can be applied to accurately quantify miR-122 in cancerous cell lysates which is in excellent agreement with the results from a commercial miRNA detection kit. This method is simple, cost-effective, highly selective, and free of dye label and separation procedures. PMID- 26258183 TI - Conversion of levulinic acid into gamma-valerolactone using Fe3(CO)12: mimicking a biorefinery setting by exploiting crude liquors from biomass acid hydrolysis. AB - The conversion of biomass-derived levulinic acid (LA) into gamma-valerolactone (GVL) using formic acid (FA) and Fe3(CO)12 as the catalyst precursor was achieved in 92% yield. To mimic a biorefinery setting, crude liquor (containing 20% LA) from the acid hydrolysis of sugarcane biomass in a pilot plant facility was directly converted into GVL in good yield (50%), without the need for isolating LA. PMID- 26258184 TI - Self-assembly formation of a healable lanthanide luminescent supramolecular metallogel from 2,6-bis(1,2,3-triazol-4-yl)pyridine (btp) ligands. AB - The synthesis of five new 2,6-bis(1,2,3-triazol-4-yl)pyridine (btp) ligands is described: the self-assembly behaviour of the tri-methyl ester, 1, with Eu(III) showed the formation of a luminescent 1:3 Eu : btp complex, Eu13, which was studied in solution and in the solid state; while the tri-carboxylic acid, 2, formed a hydrogel and its corresponding complex Eu23, gave rise to a strongly red luminescent healable metallogel. PMID- 26258185 TI - Editor's Note. PMID- 26258186 TI - A tribute to Cecile Wandersman. PMID- 26258187 TI - Author's reply. PMID- 26258188 TI - Author's reply. PMID- 26258189 TI - Author's reply. PMID- 26258190 TI - Alan Hall (1952-2015). PMID- 26258191 TI - High-sensitivity CRP: possible link between job stress and atherosclerosis. AB - BACKGROUND: Chronic inflammation may play an important role in linking job stress to atherosclerosis. We sought to investigate the relationship between job stress and high-sensitivity C-reactive protein (hs-CRP) among Chinese workers. METHODS: A total of 731 subjects (506 men and 225 women) were analyzed. Job stress was evaluated by effort-reward imbalance (ERI) model. RESULTS: Among men, after adjustment for confounders, effort, overcommitment, and ERI were significantly positively correlated with hs-CRP; and reward was significantly inversely related with hs-CRP; high level of effort, overcommitment, or ERI, respectively, significantly increased the odds of high hs-CRP with ORs of 2.0, 3.5, and 3.3 (all P<0.001), compared with the corresponding low level groups. Among women, high overcommitment or ERI also increased risk of high hs-CRP with ORs of 2.8, and 4.1 (P<0.05). CONCLUSIONS: High effort, overcommmitment, and ERI were positively associated with hs-CRP. Inflammation indicated by hs-CRP may be one of important mediators linking job stress and atherosclerosis. PMID- 26258192 TI - Headache education 2015 and beyond! PMID- 26258193 TI - Inactivity increases risk of developing dementia. PMID- 26258194 TI - Nurse practitioner gains prestigious fellowship. PMID- 26258195 TI - Rates in golden staph drop. PMID- 26258196 TI - School nurses to be reinstated. PMID- 26258197 TI - Staffing issues linked to ward suicides. PMID- 26258198 TI - Prevention of Occupational Violence and Aggression in Healthcare. PMID- 26258199 TI - Alcohol and drug use raise health concerns in older Australians. PMID- 26258200 TI - Is this how we treat nurses? PMID- 26258201 TI - The next big challenge for EPs: The transition to ICD-10-CM coding system. AB - The long-delayed transition to the International Classification of Diseases, Clinical Modification administrative codes (lCD-10-CM) is set to take place in October, presenting a host of challenges for EPs. A new analysis suggests roughly a quarter of the clinical encounters that take place in the ED will involve complexity in the transition to the new system. Further, experts anticipate workflow challenges as well as new considerations when making planning decisions and reporting to public health departments. The number of codes available to providers will jump from 14,000 to 80,000 with the transition to the new coding system. Investigators found that that 23% of the visits, or 27% of the codes, emergency medicine physicians use are complex. The new coding system requires much more specificity, but there are also instances in which definitions have been altered or blended together, essentially changing the concepts described. While all EPs will face some challenges with the new coding system, analysts are particularly concerned about smaller EDs and physician groups because these practices typically don't have the ICD-10-CM implementation teams that larger systems have. PMID- 26258202 TI - Simplified approach for delivering medicine to patients with severe pain shows promise. AB - A new study suggests that in a busy emergency environment, a protocol based on simply asking patients if they need more pain medicine at 30-minute intervals can be effective at controlling pain, although some experts urge stricter limits on the automatic authorization of hydromorphone, and a mechanism to keep physicians more involved in care. Experts suggest that soliciting patient input is more effective than relying on numbered pain scales to gauge whether pain has been adequately controlled. For non-elderly patients in severe pain, the protocol includes an automatic authorization for an additional milligram of hydromorphone up to four times at 30-minute intervals. Study results indicate that all but two of 207 study participants achieved satisfactory pain control at one or more points in the study, and that most were satisfied with their treatment. PMID- 26258203 TI - Patients more likely to engage in treatment at 30 days when given buprenorphine in the ED, referred for follow-up. AB - A new randomized trial shows patients who present to the ED with opioid dependence are much more likely to engage in treatment when they receive buprenorphine along with coordinated follow-up than when they just receive a brief intervention and a facilitated referral for treatment or just screening and referral. However, barriers to prescribing are robust, and many ED leaders are not persuaded they should be in the business of providing treatment for addiction. In the trial, at 30 days 78% of patients in the buprenorphine group (89 of 114 patients) were engaged in addiction treatment, compared with just 45% of the patients in the brief intervention group (50 of 111 patients) and 37% of patients in the referral group (38 of 102 patients). To prescribe buprenorphine for addiction disease, providers must undergo training and pass a test to obtain a DEA waiver; they are limited to treating 100 patients. While experts note there are not enough providers to prescribe buprenorphine and provide the follow-up needed to patients with addiction disease, they also acknowledge concerns about drug diversion as well as potential problems with capacity if EDs take a larger role in treating addiction. PMID- 26258204 TI - New species of Hermanella complex (Ephemeroptera: Leptophlebiidae) from Brazilian Atlantic Forest. AB - In the present work, based on material from Brazilian Atlantic Forest, four new species of the Hermanella complex are described. The main characteristics that distinguish the new species from its congeners are, in Hermanella amere sp. nov.: (1) subgenital plate yellow, with wide projection near base of forceps; (2) penis lobe with ventral, robust, posterioly directed spine; in Hermanella nigra sp. nov.: (1) subgenital plate brown washed with gray, with wide projection near inner base of forceps; (2) penis lobe with a distomedial membranous projection and ventral, robust, posteriorly directed spine; in Hylister obliquus sp. nov.: (1) subgenital plate yellowish brown, with pointed projection near inner base of forceps; (2) penis lobe with ventral, short, narrow, posteromedially directed spine; in Traverella insolita sp. nov.: (1) subgenital plate strongly projected posteriorly, forming three broad and short projections; (2) penis lobe laterally sinuous and apically rounded, with a ventral, long, narrow spine curved toward the midline of the body. Modified keys of male imagos are provided for the three genera, whereas comments regarding their taxonomy are presented. Additionally, Hermanella mazama (Nascimento, Mariano & Salles 2012 in Lima et al. 2012), comb. nov., is proposed. PMID- 26258205 TI - Two new species of Rhodacaridae (Acari: Mesostigmata) from Egypt and a key to the species of the family from the Mediterranean region. AB - Two species of rhodacarid mites, Multidentorhodacarus aegypticus n. sp. and Protogamasellopsis zaheri n. sp., are de- scribed from adult females and males collected from soil and litter in Egypt. A key to identify the species of Rhodacaridae reported from the Mediterranean region is provided. PMID- 26258206 TI - Four new species of the subfamily Psilodercinae (Araneae: Ochyroceratidae) from Southwest China. AB - Four new species of the family Ochyroceratidae are described from Southwest China: Althepus christae sp. nov., Lecler- cera undulatus sp. nov., Psiloderces incomptus sp. nov. from Yunnan; and P. exilis sp. nov. from Guangxi. The four spe cies belong to the subfamily Psilodercinae. PMID- 26258207 TI - Occurrence in Japan of Frankliniella hemerocallis (Thysanoptera, Thripidae), with description of the larva and key to Frankliniella species from Japan. AB - The occurrence in Japan of the daylily thrips, Frankliniella hemerocallis, is confirmed. This thrips probably originated in Asia or Eurasia, because it is highly specific to Hemerocallis [Liliaceae] which is native to these areas. This thrips feeds on leaf, stem and petals rather than pollen. The second instar larva is described, and a key provided to the adults of Frankliniella species recorded from Japan. PMID- 26258208 TI - New records of Black Fungus Gnats (Diptera: Sciaridae) from New Caledonia, with the description of two new Bradysia species and an updated checklist. AB - The black fungus gnats Bradysia similigibbosa sp. n. and B. irwini sp. n. are described and new records of species of Bradysia Winnertz, Ctenosciara Tuomikoski, Epidapus Haliday, Pseudolycoriella Menzel & Mohrig, and Scatopsciara Edwards are presented for New Caledonia. A checklist of the sciarids of New Caledonia is given. PMID- 26258209 TI - A new species and new record of Reticulolaelaps Costa (Acari: Laelapidae) from Iran. AB - We describe a new species of mite from Iran--Reticulolaelaps hallidayi Joharchi, Nemati & Babaeian sp. nov. (Acari: Laelapidae). The new species was collected in a nest of Tapinoma sp. (Hymnoptera: Formicidae) in Taleghan city, Alborz Province and in soil in Khuzestan province in southwestern Iran. Reticulolaelapsfaini is reported for the first time from Iran. The genus Reticulolaelaps is redescribed, and Reticulolaelaps lativentris Karg is transferred to Pseudoparasitus Oudemans. PMID- 26258210 TI - A new species of Hydrogamasellus (Acari: Mesostigmata: Ologamasidae) from Brazil, with a key to the world species of the genus. AB - Hydrogamasellus alagoensis n. sp. is described based on the morphology of adult females and males collected from litter in the State of Alagoas, Brazil. Six new combinations are proposed, namely A cugamasus avium (Karg, 1976) n. comb., Ologamasus lanceolatus (Karg, 1976) n. comb., Ologamasus microcrinis (Karg, 1979) n. comb., Ologamasus testudinis (Karg, 1976) n. comb., Rykellus longopilus (Karg, 1976) n. comb. and Rykellus ubatubaensis (Hirschmann, 1966) n. comb., and a key for the separation of females of the eighteen recognizable world Hydrogamasellus species is provided. PMID- 26258211 TI - A new species of Prosopistoma (Ephemeroptera: Prosopistomatidae) from China with a key to Oriental species. AB - A new species of the monogeneric family Prosopistomatidae, Prosopistoma ocellatum sp. n., is described and illustrated based on mature larval stages from Guangxi and Hainan, southern China. The new species can be readily distinguished from the other members of Prosopistoma by the following combination of characters: antenna 6-segmented, segment III much longer than segments IV-VI; three bristles at the base of the inner canine; 10-11 pectinate setae on ventral margin of fore tibiae, ventral and basal half surface of all femora with dense scale-like structures, and color pattern of eye-spot on the mesonotum. An update key to the known Oriental species is provided. PMID- 26258212 TI - Sunagocia omanensis, a new flathead fish (Scorpaeniformes, Platycephalidae) from the Western Indian Ocean, with comments on the distribution of Sunagocia carbuncular. AB - A new species of Platycephalidae having a weak development of sensory tubules on the cheek is placed in the genus Sunagocia Imamura. The description is based on two specimens taken at the Kuria Muria Ids., Oman. The new species may be distinguished from its congeners by having three preocular spines, ethmoid spines forming a rosette on mid-line with 5-6 tips coming from a common base, and a body coloration of tan with dark saddles reaching to lower sides. It is also characterized by having numerous small serrations along the supraorbital and suborbital ridges and sixgill rakers. A section concerning the status and range of Sunagocia carbuncula Valenciennes in the western Indian Ocean is also included. A key separating the species of Sunagocia appears below. PMID- 26258213 TI - Molecular phylogeny of the weevil genus Dichromacalles Stuben (Curculionidae: Cryptorhynchinae) and description of a new species. AB - A molecular phylogeny of the western Palearctic weevil genus Dichromacalles Stuben, 1998, is presented, combining two mitochondrial genes, COI and 16S, and the nuclear gene 28S in a Bayesian analysis of up to 1528 combined nucleotide positions. Based on this data we point out the putative ancestor of the currently known extant Dichromacalles species that initiated the unique radiation within the species of the formerly Acalles s.l. on the Canary Islands around 10 to 20 million years ago. Where morphology reaches its limits in species differentiation, molecular analysis can provide deeper insight. By combining morphology and molecular biology into an integrative taxonomy, new characters can be found, making phenotypic descriptions easier. Using this integrative taxonomy background, the new species Dichromacalles algecirasensis Stuben (Spain: Cadiz) is described here and D. lentisci (Chevrolat, 1861) is transferred into the subgenus Balcanacalles Stuben & Behne, 1998 following a molecular phylogenetic reconstruction. A catalogue of all 12 species of Dichromacalles is given and a key is presented, combined with image stackings of the habitus and aedeagus for all species. PMID- 26258214 TI - Classification and relationships of Assiculus and Assiculoides (Teleostei: Pseudochromidae). AB - The monotypic Australian pseudochromid fish genera Assiculus and Assiculoides had been previously included in the subfamily Pseudochrominae on the basis of symplesiomorphic characters. Osteological synapomorphies are identified in support of a closer relationship to the remaining pseudochromid subfamilies. Two synapomorphies (five or fewer infraorbital bones, haemal spine of preural vertebra 2 attached to centrum) diagnose a clade consisting of Assiculoides, Pseudoplesiopinae, Anisochrominae and Congrogadinae. Two additional synapomorphies (parhypural not separate from hypurals 1+2, total caudalfin rays modally 27 or fewer) diagnose a more inclusive clade that also includes Assiculus. Two new subfamilies are erected to reflect these relationships. PMID- 26258215 TI - Review of the Argentinean species of Pseudomicrocara Armstrong (Coleoptera: Scirtidae). AB - The Pseudomicrocara Armstrong from Argentina are reviewed. In total, seven species are present: Pseudomicrocara angusta sp. nov., P. antarctica (Fairmaire) comb. nov., P hieroglyphica sp. nov., P. inflexipenis sp. nov., P livida (Fabricius), P. obliquata (Solier) comb. nov., and P patagonica (Curtis) comb. nov. New provincial records are provided for several species. Pseudomicrocara obliquata, previously known only from Chile, is recorded from Argentina for the first time. Illustrations of habitus and genitalia as well as distributional data for all Argentinean species of Pseudomicrocara are provided. PMID- 26258216 TI - Review of the subfamily Tripetalocerinae Bolivar, 1887 (Orthoptera: Tetrigidae). AB - Subfamily Tripetalocerinae consist of four genera distributed in Southeast Asia. Clinophaestus gen. nov. (type species: Clinophaestus robustus sp. nov.) and Tripetaloceroides gen. nov. (type species: Tripetalocera tonkinensis Gunther, 1938) are described. New tribe Clinophaestini trib. nov. (type genus: Clinophaestus gen. nov.) is established. Diagnosis and key to tribes and genera are given. An annotated list of species is provided. Genus Kraengia Bolivar, 1909 is transferred from Tripetalocerinae to Discotettiginae. PMID- 26258217 TI - Three species of Culicoides Latreille (Diptera: Ceratopogonidae) newly recorded from the Republic of Korea. AB - Light trap surveys of adult Culicoides Latreille in the Republic of Korea (ROK) resulted in the capture of three previously unreported species, C. nasuensis Kitaoka, C. pallidulus Yu and C. jacobsoni Macfie. These new records are supported by supplementary morphological descriptions and DNA barcodes (mitochondrial cytochrome oxidase I or COI). An updated checklist of species reported from the ROK is provided. PMID- 26258218 TI - Echiniscus semifoveolatus (Heterotardigrada: Echiniscidae), a newly recorded species from China. AB - Echiniscus semifoveolatus Ito, 1993 (Tardigrada: Echiniscidae) is reported as a new record for China, and was collected from the Mt. Jinggang, Jiangxi, and the Wuyi Mountains, south-eastern China. This is the first report of this species from outside the type locality, Mt. Fuji, central Japan. The number of dorsal spines that arise from the posterior edge of the scapular plate ranges from zero to five while the type specimen has two symmetrically arranged spines at Bd. The distance between the spines varies. These variations in both the number of spines and the distance between the spines could be considered as individual variation. We provide a detailed supplementary description for this species based on the Chinese specimens and supply a key to all known Chinese species of the genus Echiniscus. PMID- 26258219 TI - Two new Aphnaeus (Lepidoptera: Lycaenidae: Theclinae) species from Liberia. AB - Two new butterfly species belonging to the genus Aphnaeus (Lycaenidae: Theclinae), A. mirabilis sp. n., A. nimbaensis sp. n. were found in the Nimba Mountains, Western Range, Liberia in February 2012. Both are illustrated and described in comparison with closely related species: A. flavescens Stempffer, 1954 and A. liberti Bouyer, 1996, respectively. Genitalia of the male holotype of A. nimbaensis are also illustrated. PMID- 26258220 TI - An annotated catalog of the Iranian Reduvioidea (Hemiptera: Heteroptera: Cimicomorpha). AB - An updated list of Iranian Reduvioidea Latreille (families Pachynomidae, Reduviidae) is presented and discussed in this paper. For Iranian fauna, there are records of one species of Pachynomidae and 109 species and subspecies of assassin bugs (Reduviidae) distributed in 24 genera and subgenera, and seven subfamilies, Emesinae, Harpactorinae, Holoptilinae, Peiratinae, Phymatinae, Reduviinae, and Stenopodainae. We report 6 new country records and one new species, Empicoris baerensprungi (Dohrn, 1863) for Asian fauna. Synonyms and distribution data are also given. PMID- 26258221 TI - Studies of Madagascan Ptiliidae (Coleoptera) 1: The Tribe Discheramocephalini including eighteen new species. AB - This is the first report detailing Ptiliidae collected from forest leaf litter by the Moravian Museum expeditions to Madagascar 2010-2011.18 new species in three genera are described and figured: Discheramocephalus bisulcatus sp. n.; D. vasilii sp. n.; Cissidium banari sp. n.; Dacrysoma andasibense sp. n.; D. imitatuin sp. n.; D. delicatum sp. n.; D. denticulatum sp. n.; D. dolorosum sp. n.; D. fabrum sp. n.; D. fusum sp. n.; D. longulum sp. n.; D. nigerrimum sp. n.; D. pilosum sp. n.; D. rahanitriniainae sp. n.; D. ranomafanense sp. n.; D. ravelosoni sp. n.; D. subinsulsum sp. n.; and D. varium sp. n. PMID- 26258222 TI - On the phylogenetic position of Carollia manu Pacheco et al., 2004 (Chiroptera: Phyllostomidae: Carolliinae). AB - The Neotropical bat genus Carollia (Phyllostomidae: Carolliinae) currently includes eight species. Carollia manu was described in 2004 and is distributed in montane forests in southern Peru and Bolivia. The phylogenetic affinities of C. manu have never been assessed before. Phylogenetic analyses of cytochrome b sequences of seven of the eight known species of the genus place C. manu sister to C. subrufa. The analyses also suggest hidden diversity in the genus. PMID- 26258223 TI - Descriptions of two new species of Gonatocerus (Hymenoptera: Mymaridae) from southeastern Europe. AB - Two new taxa, Gonatocerus (Lymaenon) bulgaricus Donev & Triapitsyn (Bulgaria, and also apparently mainland Greece) and G. (Lymaenon) mediterraneus Donev & Triapitsyn (Greece-Crete Island) are described, diagnosed, and illustrated. Also, a species tentatively identified as G (Lymaenon) ?beshbarmak Triapitsyn is reported from mainland Greece. If the species is indeed G. beshbarmak then this is the first record of it from Greece. PMID- 26258225 TI - On the correct name of Icterus bullockii (Passeriformes: Icteridae). PMID- 26258224 TI - A new species of Helobdella (Hirudinida: Glossiphoniidae) from Oregon, USA. AB - Helobdella bowermani n. sp. is described from specimens collected in fine sediment of open water benthos of Upper Klamath Lake, Klamath County, Oregon. The new species has pale yellow/buff coloration with scattered chromatophore blotches throughout the dorsal surface, lateral extensions or papillae only on the a2 annulus, dorsal medial row of papillae with small papilla on al and larger papillae on a2 and a3, and a small oval scute (rarely triangular). Helobdella bowermani n. sp. is morphologically similar to Helobdella atli and Helobdella simplex. Molecular comparison of CO-I sequence data from H. bowermani n. sp. revealed differences of 10.6/--10.8% with Helobdella californica, differences of 12.2%-13.7% with H. atli, and differences of 12.7%-13.2% with H. simplex. PMID- 26258226 TI - The gender of "cleis": correct spelling of Chiasmocleis supercilialbus Morales and McDiarmid, 2009, and Elachistocleis magnus Toledo, 2010 (Anura, Microhylidae). PMID- 26258227 TI - The advertisement call and clutch size of the Golden-capped Boulder-frog Cophixalus pakayakulangun (Anura: Microhylidae). PMID- 26258228 TI - Embryology of the spider crabs Leurocyclus tuberculosus (H. Milne-Edwards & Lucas 1842) and Libinia spinosa (H. Milne-Edwards 1834) (Brachyura, Majoidea). AB - The embryonic development of the spider crabs Leurocyclus tuberculosus and Libinia spinosa was divided into five periods based on the differentiation of: (I) cleavage, (II) embryonic primordium, III) optic lobes, (IV) optic lobes pigmented and (V) chromatophores presence. Different traits such as spines, setae and telson morphology distinguish the two species from period III until hatching. Egg volume was greater in Leurocyclus tuberculosus than in Libinia spinosa. The duration of each period was different during development. Whereas in Leurocyclus tuberculosus period II (morphogenesis) is the longest, in Libinia spinosa the period IV is the longest. Complete embryonic development at 14'C lasted 36.7 +/- 3.1 days in Leurocyclus tuberculosus and 57.4 +/- 4.4 days in Libinia spinosa. PMID- 26258229 TI - New species of subgenus Megaluracarus (Acari: Hydrachnidiae: Arrenuridae: Arrenurus) from Mexico. AB - Four new water mite species of the subgenus Arrenurus (Megaluracarus) from lakes and ponds in Mexico are described and illustrated: Arrenurus (Megaluracarus) anitahoffmannae sp. nov., A. olmeca sp. nov., A. maya sp. nov., and A. urbanus sp. nov. With these species the number of known species of this subgenus in Mexico increases to 21. PMID- 26258230 TI - Annotated checklist of the flat bug family Aradidae Brulle, 1836 from East Africa (Hemiptera, Heteroptera). AB - The flat bug fauna of East African countries has never been the subject of a comprehensive study. Most descriptions and distribution data are from colonial times, with most records coming from what is present day Tanzania, Rwanda and Burundi. In this checklist, the data from all available literature was assembled, and references are given for 16 genera and 37 species. PMID- 26258231 TI - The genus Mycterothrips (Thysanoptera: Thripidae) in Iran, with three new species. AB - Three new species of Mycterothripsare described from Khorasane Shomali province in Northeast of Iran, M. mahvelatensis sp.n., M. nastarani sp.n. and M. sanubari sp.n.. An identification key is provided for both sexes of the nine species of Mycterothrips known from Iran. Host associations among these Iranian species, as well as the variation in number of pronotal posteromarginal setae, are discussed briefly. PMID- 26258232 TI - Samadinia longispina, a new genus and species of deep-sea spider crab from the western Pacific, and a new species of Rochinia A. Milne-Edwards, 1875, from Papua New Guinea (Crustacea: Brachyura: Majoidea: Epialtidae). AB - A new genus, Samadinia n. gen., and new species, Samadinia longispina n. sp., of deep-water epialtid spider crab is described from French Polynesia and New Caledonia. The new genus is superficially similar to Rochinia A. Milne-Edwards, 1875, but can be distinguished by having the dorsal surface of the carapace covered with small, rounded granules (versus with long spines or strong tubercles), well developed hepatic and lateral branchial spines (versus relatively shorter and weaker), a prominently constricted male thoracic sternite 4 (versus relatively broader with less prominent or without median constriction) and a proportionally broader male abdomen. A new species of Rochinia, R. granulosa n. sp., is also described from Papua New Guinea. It is easily distinguished from congeners its small adult size, the presence of numerous relatively large granules on the carapace and a relatively short hepatic spine. PMID- 26258233 TI - A new fish species of the Genus Hapalogenys (Perciformes: Hapalogenyidae) from the Bay of Bengal, India. AB - A new species of the genus Hapalogenys, Hapalogenys bengalensis sp. nov. is described from fourteen specimens collected from the Bay of Bengal coast. The species is distinct in having three longitudinal dark stripes; pelvic-fin tip almost reaching the base of first anal-fin spine when depressed; transverse scale rows above lateral line 7-8, below lateral line 19-20; gill rakers 18 (7 on lower limb and 11 on upper limb); posterior angle ofjaw reaching vertical through anterior rim of eye. Genetic divergence (13.0-14.2%) and analysis of NJ tree shows that the new species is closely related to H. kishinouyei in the "Hapalogenys kishinouyei complex" with significant morphological difference from the other three species reported from the same complex. PMID- 26258234 TI - Two new species of the genus Anemadus Reitter, 1885, from the Near East (Coleoptera: Cholevidae). AB - Two new species of Anemadus from the Near East are described and illustrated. Anemadus lucarellii sp. nov., from South-Western Anatolia, belongs to the Anemadus pellitus species-group (sensu Giachino & Vailati, 1993) and Anemadus kadleci sp. nov., from North-Western Syria, belongs to the Anemadus strigosus species-group (sensu Giachino & Vailati, 1993). The description of these new species markedly increases the knowledge of the distribution of this genus in the Near East. PMID- 26258235 TI - On the fauna of Cossidae (Lepidoptera) of Zimbabwe with description of a new species. AB - The annotated list of Cossidae of Zimbabwe consists of 15 species in 9 genera from the subfamilies Cossinae and Zeuzerinae. The species Brachylia vukutu Yakovlev & Lenz, sp. nov. is newly described. PMID- 26258236 TI - Advertisement call of Zachaenus carvalhoi Izecksohn, 1982 (Anura: Cycloramphidae) from southeastern Brazil. PMID- 26258237 TI - Taxonomic revision of Mesamphiagrion Kennedy, 1920 from Colombia (Odonata: Coenagrionidae), with the description of four new species. AB - The genus Mesamphiagrion Kennedy, 1920, occurs in the Pantepui region and northern Andes in South America and is most speciose in Colombia where the genus is less known. In this work, we record 10 species of Mesamphiagrion from Colombia, including four new species (Mesamphiagrion gaudiimontanum Bota-Sierra sp. nov., M nataliae Bota-Sierra sp. nov., M. rosseri Bota-Sierra sp. nov., and M. santainense Bota-Sierra sp. nov.). We also redescribe the male of M risi (De Marmels 1997) and describe the females of M. risi, M. ovigerum (Calvert, 1909), and M occultum (Ris, 1918), which were previously unknown. Descriptions, photographs, illustrations, distribution maps, natural history notes, and a diag nostic key for males and females of Mesamphiagrion from Colombia are provided. PMID- 26258238 TI - Rothilena (Araneae: Agelenidae), a new genus of funnel-web spiders endemic to the Baja California Peninsula, Mexico. AB - Rothilena (Araneae: Agelenidae: Ageleninae), a new genus of funnel-web spiders endemic to the Baja California Peninsula in Mexico, and six new species (Rothilena griswoldi sp. nov., Rothilena cochimi sp. nov., Rothilenapilar sp. nov., Rothilena golondrina sp. nov., Rothilena sudcaliforniensis sp. nov., and Rothilena naranjensis sp. nov.) are described and illustrated. Males are diagnosed by having pedipalps with a conductor with three projections and a retrolateral tibial apophysis divided in two parts, one distal and dorsally excavated and the other retrolateral and ventrally excavated. The epigynum of females has a pair of hoods that covers part of the atrium, and the copulatory ducts resemble a "duck head". PMID- 26258239 TI - A new species of Liropus (Crustacea, Amphipoda, Caprellidae) from California, U.S.A., with an illustrated key of the genus. AB - A new species of the genus Liropus (Crustacea, Amphipoda, Caprellidae) is described based on specimens collected from a small cave of Santa Catalina Island, California. The new species, Liropus minusculus, can be distinguished from all its congeners mainly by the presence of anterolateral projections on pereonites 2, 3, and 4 (males), pereopod 5 one-articulate (although with a second article incompletely tabicated), basis of gnathopod 2 very elongate (males), and abdomen with two pairs of one-articulate appendages (males), one of them rudimentary. Up-to-date morphological comparisons among the world Liropus species are provided, together with an illustrated key to species. This is the first record of Liropus from the north-east Pacific. PMID- 26258240 TI - Smetanabatrus kinabalu (Staphylinidae: Pselaphinae: Batrisitae), a new genus and new species from Sabah, Borneo. AB - A new genus and new species of the pselaphine tribe Batrisini, Smetanabatrus kinabalu gen. et sp. n., is described from Sabah, East Malaysia. Both sexes of the new species have securiform maxillary palpi, with the male exhibiting extreme abdominal modification. Illustrations of the habitus and major diagnostic features, as well as a discussion on the taxonomic placement of the new taxon is provided. A key to genera of the Batrisini from Borneo is provided. PMID- 26258241 TI - Myrmicella, a new genus of Harpactorinae (Hemiptera: Heteroptera: Reduviidae) from Madagascar. AB - Myrmicella verticospinosa gen. et sp. nov., is described, based on four specimens (two males and two females) collected in south-west Madagascar (Zombitse Vohibasia National Park and Isalo National Park). Three specimens have been collected by sifting the leaf litter, one female was collected using yellow pan traps. Genitalia of both sexes are described and illustrated. PMID- 26258242 TI - A new species of frogfish of the genus Kuiterichthys (Lophiiformes: Antennariidae: Histiophryninae) from New South Wales, Australia. AB - Kuiterichthys pietschi, a new species of frogfish of the teleost order Lophiiformes, family Antennariidae, subfamily Histiophryninae, is described from 20 specimens collected at depths of 60-89 m (average 73 m) off New South Wales, Aus- tralia. A member of the antennariid genus Kuiterichthys, the new species differs from its congener in escal morphology, a somewhat shorter second dorsal fm spine (17.0-22.5% SL vs. 17.8-29.8%); 20 vertebrae vs. 21; 10-11 dorsal-fin rays vs. 12-14; and 7-8 pectoral-fm rays vs. 9-10. The new species is described and compared with its purported sister species, Kuiterichthysfurcipilis. PMID- 26258243 TI - On Tetragonicipitidae (Crustacea, Copepoda) from the Channel of Sao Sebastiao, Brazil, with description of their nauplii and two new species of Phyllopodopsyllus. AB - Phyllopodopsyllus iuanamai sp. nov. and Phyllopodopsylluspseudokunzi sp. nov. are described from specimens collected in the Channel of Sao Sebastiao (State of Sao Paulo, Brazil). The nauplii of P. iuanamai, P. pseudokunzi, P aegypticus Nicholls, 1944 are described, additional information is given on nauplii and morphology of the adult P. setouchiensis Kitazima, 1981, and on the nauplius of Laophontella horrida (Por, 1964). These represent first records of P. aegypticus and L. horrida in Brazilian waters. PMID- 26258244 TI - Four new species of Plakinidae (Porifera: Homoscleromorpha) from Brazil. AB - Seven species of Plakinidae are currently known from Brazil, belonging to genera Plakina (P. trilopha), Plakinastrella (P. microspiculfera, P. onkodes), and Plakortis (P. angulospiculatus, P. halichondrioides, P. insularis, and P microrhabdifera). In this study we describe four new species of the genera Plakinastrella and Plakortis, increasing the number of plakinid species in Brazil to eleven. Plakortis petrupaulensis sp. nov. is encrusting, light brown; the skeleton is disorganized with few traces of reticulation; lacunae are absent; the spicules are diods and tuberculate microrhabds; spheres are common and triods are absent. Plakortis spinalis sp. nov. is encrusting, gray, cartilaginous, has a reticulated ectosomal skeleton, and is distinguished by the spines in some of the diods and triods; microrhabds are also tuberculate and smooth spheres are common. Plakortis potiguarensis sp. nov. is encrusting, brown with gray tinges, and cartilaginous; the skeleton is disorganized and scarce, composed of thin, irregular diods, triods and relatively large microrhabds. Plakinastrella globularis sp. nov. has a globular shape and dark blue color in vivo; the ectosomal skeleton has a double tangential reticulation and the choanosomal skeleton is reticulated. The spicules are diods, triods, calthrops and microrhabds; spheres are common. Two of the new species have characters previously unknown in their respective genera: the spined diods and triods of Plakortis spinalis sp. nov. and the blue color and microrhabds of Plakinastrella globularis sp. nov. The presence of microrhabds in Plakinastrella suggests a close relationship of this genus with Plakortis. PMID- 26258245 TI - Taxonomic notes on Pternoscirtapulchripes Uvarov, 1925 (Orthoptera: Acrididae: Oedipodinae) with proposal of new synonyms in the genera Flatovertex and Mioscirtus. AB - Based on the examination of types and additional materials, the morphology of Pternoscirtapulchripes Uvarov, 1925 and Flatovertex species were reviewed. As a result of our study, the genus Flatovertex Zheng, 1981 was synonymized with the genus Pternoscirta Saussure, 1884, the species Flatovertex cyaneitibialis Zhang & Han, 2010 was synonymized with Pternoscirta caliginosa (Haan, 1842), Flatovertex rufotibialis Zheng, 1981 with Pternoscirta pulchripes Uvarov, 1925, and Flatovertex nigritibialis Zheng & Zhang, 2006 with Mioscirtus wagneri wagneri (Eversmann, 1859), respectively. Mioscirtus varentzowi Zubowsky, 1896 was considered as a junior synonym of Mioscirtus wagneri wagneri (Eversmann, 1849) but not that of Mioscirtus wagneri rogenhoferi (Saussure, 1888). PMID- 26258246 TI - A molecular and morphological characterization of Oliver's parrot snake, Leptophis coeruleodorsus (Squamata: Serpentes: Colubridae) with the description of a new species from Tobago. AB - Currently, two snake species of the genus Leptophis occur in Trinidad and Tobago. One, L. stimsoni, is endemic to Trinidad's Northern Range and known from relatively few specimens. The second is the diurnal, arboreal, brightly colored parrot snake Leptophis coeruleodorsus Oliver. It was originally described based on 23 specimens from Trinidad, Tobago, and four locations in northern Venezuela but remains poorly known. It was later assigned as a subspecies of Leptophis ahaetulla; a widespread, polytypic species. Here we compare 11 specimens of the L. ahaetulla Group using DNA sequences from two mitochondrial genes (cytochrome b and 16S, 1,383 bp total) from island and mainland populations, report on the variation in the morphology of 54 museum specimens of Leptophis a. coeruleodorsus; describe the previously undescribed holotype of L. coeruleodorsus Oliver, and restrict its type locality. Additionally, we describe a new species of Leptophis from the island of Tobago that can be distinguished from L. coeruleodorsus on the basis of snout shape, upper labial architecture, elongated prefrontal scales, and ventral scale counts. The new Leptophis raises the number of endemic Tobago amphibians and reptiles to 11 taxa. PMID- 26258247 TI - Four new species of Phyllomyza Fallen from China (Diptera, Milichiidae). AB - The following four species of the genus Phyllomyza Fallen from China are described as new to science: P. angustigenis sp. nov., P. cuspigera sp. nov., P. clavellata sp. nov., and P euthyipalpis sp. nov. A key to the known species of Phyllomyza from China is presented. PMID- 26258248 TI - Schistura maculosa, a new species of loach (Teleostei: Nemacheilidae) from Mizoram, northeastern India. AB - Schistura maculosa, a new species of loach, is described from Tuingo and Pharsih Rivers, tributaries of Tuivai River (Barak drainage) in Mizoram, northeastern India. It is distinguished from other closely related Schistura species in having an axillary pelvic lobe; an incomplete lateral line; 20-30 narrow black bars on the body; 3-4 rows of black spots horizontally across the dorsal-fin; a slightly emarginate caudal-fin, with 5-7 rows of black spots more or less regularly arranged vertically on rays across the fin, and 8+8 branched caudal-fin rays. PMID- 26258249 TI - Three new species of the genus Ripeacma (Lepidoptera: Oecophoridae) from China. AB - Three new species of the genus Ripeacma Moriuti, Saito et Lewvanich, 1985 are described based on specimens collected in China: R. quadridigitata sp. nov. from Guizhou, R. damingshana sp. nov. from Guangxi, and R. magnihamata sp. nov. from Fujian. Images of adults and genitalia are provided. PMID- 26258250 TI - Description of the adult male of Aeschnosoma auripennis Geijskes, 1970 (Odonata: Corduliidae s.s.). AB - The male of A eschnosoma auripennis is described for the first time, based on a specimen reared from a larva collected in the Reserva Biologica do Uatuma, Amazonas State, Brazil. The species is newly reported from the Roraima State, Brazil. PMID- 26258251 TI - Cryoconservation of Chicken Blastodermal Cells: Effects of Slow Freezing, Vitrification, Cryoprotectant Type and Thawing Method during In Vitro Processing. AB - Cryoconservation of blastodermal cells (BCs) can preserve genetic material for the future reconstruction of poultry breeds. The aim of our study was to compare the effects of three slow freezing programs and vitrification, different cryoprotectants (5% DMSO, 10% DMSO, or multi-component cryoprotectant (MC) and two thawing methods on the viability of chicken BCs. Significant differences in the survival of slowly frozen BCs using program 3 (2 degrees C/min. to 0.4 degrees C/min.) compared with programs 1 (1 degrees C/min. to 0.3 degrees C/min.) and 2 (4 degrees C/min. to 0.3 degrees C/min.) were observed. The percentage of live BCs was significantly higher after slow freezing in the presence of the MC compared with DMSO. The thawing method did not have a significant effect on the percentage of live BCs. We also observed significant differences in the survival rate of BCs after vitrification (81%) and slow freezing in the presence of 10% DMSO using program 3 (60%). The highest percentage of viable BCs was achieved by slow freezing with the MC using program 2 and thawing with method 1 (94%). The most unfavorable combination for BCs survival was slow freezing in 5% DMSO using program 3 and thawing with method 2 (58.3%). This is the first study to apply MC to the slow freezing of BCs. We also showed successful BCs vitrification. PMID- 26258252 TI - [Influence of pollution on respiratory and circulatory system. Review of conference dedicated memory of doctor Wojciech Lubinski]. PMID- 26258253 TI - Hierarchical Bayesian Approach To Reduce Uncertainty in the Aquatic Effect Assessment of Realistic Chemical Mixtures. AB - Species in the aquatic environment differ in their toxicological sensitivity to the various chemicals they encounter. In aquatic risk assessment, this interspecies variation is often quantified via species sensitivity distributions. Because the information available for the characterization of these distributions is typically limited, optimal use of information is essential to reduce uncertainty involved in the assessment. In the present study, we show that the credibility intervals on the estimated potentially affected fraction of species after exposure to a mixture of chemicals at environmentally relevant surface water concentrations can be extremely wide if a classical approach is followed, in which each chemical in the mixture is considered in isolation. As an alternative, we propose a hierarchical Bayesian approach, in which knowledge on the toxicity of chemicals other than those assessed is incorporated. A case study with a mixture of 13 pharmaceuticals demonstrates that this hierarchical approach results in more realistic estimations of the potentially affected fraction, as a result of reduced uncertainty in species sensitivity distributions for data-poor chemicals. PMID- 26258254 TI - Minutes of the Business Meeting of the International Society of Gynecological Pathologists, Boston, March 22, 2015. PMID- 26258255 TI - Direct Observation of Ion Pairing at the Liquid/Solid Interfaces by Surface Enhanced Raman Spectroscopy. AB - Ion-pairing, the association of oppositely charged ionic species in solution and at liquid/solid interfaces has been proposed as a key factor for a wide range of physicochemical phenomena. However, experimental observations of ion pairing at the ligand/solid interfaces are challenging due to difficulties in differentiating ion species in the electrical double layer from that adsorbed on the solid surfaces. Using surface enhanced Raman spectroscopy in combination with electrolyte washing, we presented herein the first direct experimental evidence of ion pairing, the coadsorption of oppositely charged ionic species onto gold nanoparticles (AuNPs). Ion pairing reduces the electrolyte concentration threshold in inducing AuNP aggregation and enhances the competitiveness of electrolyte over neutral molecules for binding to AuNP surfaces. The methodology and insights provided in this work should be important for understanding electrolyte interfacial interactions with nanoparticles. PMID- 26258256 TI - Detection of the Thorium Dimer via Two-Dimensional Fluorescence Spectroscopy. AB - Thorium dimer, Th2, has been detected in the gas phase via two-dimensional laser induced fluorescence electronic spectroscopy. The visible excitation spectra are broad, unstructured features with an approximate line width of 10 cm(-1). The spectrum consists of vibrational progressions associated with excitation from the ground electronic state to two different excited electronic states. The dispersed fluorescence was analyzed to give ground state vibrational constants omegae = 134.86 +/- 0.66 cm(-1) and omegaexe = 0.50 +/- 0.04 cm(-1). Vibrational constants omegae = 169 +/- 3 and 212 +/- 2 cm(-1) were determined for the two excited electronic states. The radiative lifetimes were measured. A comparison with theoretical predictions is given. PMID- 26258257 TI - Aluminum Nanoantenna Complexes for Strong Coupling between Excitons and Localized Surface Plasmons. AB - We study the optical dynamics in complexes of aluminum nanoantennas coated with molecular J-aggregates and find that they provide an excellent platform for the formation of hybrid exciton-localized surface plasmons. Giant Rabi splitting of 0.4 eV, which corresponds to ~10 fs energy transfer cycle, is observed in spectral transmittance. We show that the nanoantennas can be used to manipulate the polarization of hybrid states and to confine their mode volumes. In addition, we observe enhancement of the photoluminescence due to enhanced absorption and increase in the local density of states at the exciton-localized surface plasmon energies. With recent emerging technological applications based on strongly coupled light-matter states, this study opens new possibilities to explore and utilize the unique properties of hybrid states over all of the visible region down to ultraviolet frequencies in nanoscale, technologically compatible, integrated platforms based on aluminum. PMID- 26258259 TI - Myxozoans and Our Dinner Table: Pathogenicity Studies of Myxobolus honghuensis (Myxosporea: Bivalvulida) Using a Suckling Mice Model. AB - Myxobolus honghuensis parasitizes the pharynx of the allogynogenetic gibel carp Carassius auratus gibelio (Bloch), an economically important food fish with large consumption rates in China. The fact that it is hard to detect the cysts formed by M. honghuensis without euthanizing the fish and the spores can reach the consumers has prompted us to investigate the effect of M. honghuensis on conventional, immunocompetent BALB/c suckling mice, in order to consider the possible pathological effects in general immunocompetent consumers by the ingestion of Myxobolus-infected fish. BALB/c suckling mice were inoculated with serial dilutions of the spore suspension and then hematological and histological studies were performed. Tests of suckling mice showed no statistically difference of fluid accumulation ratio between mice inoculated with 1.65 * 10(6) M. honghuensis spores and negative control after 8-h incubation. Spores did not disrupt intestinal histology, and no abnormal bowel movements were observed within 20 h postinoculation. No anomalous hematology parameters were documented. These results, taken together, reveal that M. honghuensis spores do not cause pathology (diarrhea and elevated fluid accumulation) in BALB/c suckling mice. However, an extrapolation is not currently feasible because of lack of a highly quantifiable risk extrapolation model, inaccessibility to data for the effect of M. honghuensis on humans, and lack of consideration of the immunosuppressed population. Our study extends the results of the effect of myxozoan on suckling mice and serves as baseline for future experiment using the same model in evaluating the myxozoan-caused foodborne disease. PMID- 26258258 TI - Multi-Province Listeriosis Outbreak Linked to Contaminated Deli Meat Consumed Primarily in Institutional Settings, Canada, 2008. AB - A multi-province outbreak of listeriosis occurred in Canada from June to November 2008. Fifty-seven persons were infected with 1 of 3 similar outbreak strains defined by pulsed-field gel electrophoresis, and 24 (42%) individuals died. Forty one (72%) of 57 individuals were residents of long-term care facilities or hospital inpatients during their exposure period. Descriptive epidemiology, product traceback, and detection of the outbreak strains of Listeria monocytogenes in food samples and the plant environment confirmed delicatessen meat manufactured by one establishment and purchased primarily by institutions was the source of the outbreak. The food safety investigation identified a plant environment conducive to the introduction and proliferation of L. monocytogenes and persistently contaminated with Listeria spp. This outbreak demonstrated the need for improved listeriosis surveillance, strict control of L. monocytogenes in establishments producing ready-to-eat foods, and advice to vulnerable populations and institutions serving these populations regarding which high-risk foods to avoid. PMID- 26258260 TI - Prevalence of CTX-M-15 Extended-Spectrum beta-Lactamase-Producing Salmonella Isolated from Chicken in Korea. AB - A total of 162 Salmonella isolates were isolated in samples from poultry farms, slaughterhouses, retail chicken meats, and human feces between 2012 and 2013. All extended-spectrum beta-lactamase-producing isolates had bla(CTX-M-15) gene sequence in their plasmids. This genotype may be related to multidrug resistance. Repetitive sequence-based polymerase chain reaction patterns among CTX-M-15 isolates were classified into 12 indistinguishable groups. CTX-M-15 isolates had various plasmid replicon types; however, the most frequent type was FIIS. This result suggests that bla(CTX-M-15) could be propagated via plasmid transfer. PMID- 26258261 TI - Effects of In-Feed Copper, Chlortetracycline, and Tylosin on the Prevalence of Transferable Copper Resistance Gene, tcrB, Among Fecal Enterococci of Weaned Piglets. AB - Heavy metals, such as copper, are increasingly supplemented in swine diets as an alternative to antibiotics to promote growth. Enterococci, a common gut commensal, acquire plasmid-borne, transferable copper resistance (tcrB) gene mediated resistance to copper. The plasmid also carried resistance genes to tetracyclines and macrolides. The potential genetic link between copper and antibiotic resistance suggests that copper supplementation may exert a selection pressure for antimicrobial resistance. Therefore, a longitudinal study was conducted to investigate the effects of in-feed copper, chlortetracycline, and tylosin alone or in combination on the selection and co-selection of antimicrobial-resistant enterococci. The study included 240 weaned piglets assigned randomly to 6 dietary treatment groups: control, copper, chlortetracycline, tylosin, copper and chlortetracycline, and copper and tylosin. Feces were collected before (day 0), during (days 7, 14, 21), and after (days 28 and 35) initiating treatment, and enterococcal isolates were obtained from each fecal sample and tested for genotypic and phenotypic resistance to copper and antibiotics. A total of 2592 enterococcal isolates were tested for tcrB by polymerase chain reaction. The overall prevalence of tcrB-positive enterococci was 14.3% (372/2592). Among the tcrB-positive isolates, 331 were Enterococcus faecium and 41 were E. faecalis. All tcrB-positive isolates contained both erm(B) and tet(M) genes. The median minimum inhibitory concentration of copper for tcrB negative and tcrB-positive enterococci was 6 and 18 mM, respectively. The majority of isolates (95/100) were resistant to multiple antibiotics. In conclusion, supplementing copper or antibiotics alone did not increase copper resistant enterococci; however, supplementing antibiotics with copper increased the prevalence of the tcrB gene among fecal enterococci of piglets. PMID- 26258262 TI - Prevalence of ColV Plasmid-Linked Genes and In Vivo Pathogenicity of Avian Strains of Escherichia coli. AB - Avian pathogenic Escherichia coli (APEC) causes extraintestinal infections in birds, leading to an increase in the cost of poultry production. The ColV plasmid linked genes iroN, ompT, hlyF, iss, and iutA have previously been suggested to be predictors of the virulence of APEC. In this research, we analyzed the frequencies of these genes in a Brazilian collection of E. coli isolated from birds with colibacillosis (APEC) and from apparently healthy birds (avian fecal [A(fecal)]), as well as from the litter of poultry houses of apparently healthy flocks (avian litter [A(litter)]). All the isolates that harbored ompT also harbored hlyF, so they were considered as one trait for statistical analysis. The relationship between in vivo virulence in 1-day-old chicks, expressed as a pathogenicity score, and the number of genes in each isolate showed that isolates with less than two of the four genes were rarely pathogenic, while most pathogenic isolates contained two or more genes. Nevertheless, about half of the nonpathogenic isolates also harbored two or more genes, in agreement with previous observations that commensal E. coli isolates from the birds' microbiota can serve as a reservoir of virulence genes. Thus, the pentaplex polymerase chain reaction can be used to indicate that a strain carrying none or only one gene would be nonpathogenic, but it cannot be used to indicate that a strain with two to four genes would be an APEC. Isolates allocated to phylogenetic group B2, which is frequently associated with extraintestinal infections, had the highest pathogenicity scores, while isolates allocated to group B1 had the lowest. PMID- 26258263 TI - Development of a Method for the Analysis of Multiclass Antibiotic Residues in Milk Using QuEChERS and Liquid Chromatography-Tandem Mass Spectrometry. AB - A precise and simplified method of sample preparation for the simultaneous quantification of the antibiotics beta-lactam, macrolide, tetracycline, sulfonamide, and quinolone in bovine milk was developed. The central composite design of response surface methodology was used to design and optimize the method for the determination of six different antibiotic residues in milk. The recovery of each antibiotic was studied using a quick, easy, cheap, effective, rugged, and safe (QuEChERS) method. Octadecylsilane (C18), primary secondary amine (PSA), and sodium acetate (Na acetate) were the main factors affecting the recovery of each antibiotic. After optimization, the maximum predicted recovery rate was 84.18% for erythromycin under the optimized conditions of 101.20 mg C18, 52.00 mg PSA, and 1.01 g Na acetate. The recovery rates of the five other antibiotic residues ranged from 86.09% to 115.99%. The results suggested that modified QuEChERS could effectively be implemented in the analysis of antibiotic residues in milk. PMID- 26258265 TI - Inadequate Source Control and Inappropriate Antibiotics are Key Determinants of Mortality in Patients with Intra-Abdominal Sepsis and Associated Bacteremia. AB - BACKGROUND: Patients with intra-abdominal sepsis and associated bacteremia have a high mortality rate. However, outcomes studies in this population are limited, in part because of the small numbers of such patients. The objective of this study was to describe characteristics of critically ill patients with secondary blood stream infection (BSI) of intra-abdominal origin and identify predictors of mortality. METHODS: This retrospective, single-center study evaluated patients admitted between January 2005 and January 2011 with bacteremia because of an intra-abdominal source. Patients were included if they met criteria for severe sepsis based on International Classification of Diseases, 9th Revision (ICD 9) codes for acute organ dysfunction, had a positive blood culture, had at least one ICD 9 code indicative of an intra-abdominal process, and had a confirmed or clinically suspected intra-abdominal infection (IAI) within 72 h of the blood culture. Chart review was performed to confirm the presence of these criteria and also the absence of any other potential source of bacteremia. Data were collected on patient demographics, BSI source, source control procedure details, microorganisms isolated, and antibiotics administered. Multivariable logistic regression analysis was performed to identify independent predictors of mortality. RESULTS: Three hundred six patients with BSI were identified, of which 108 episodes were deemed to be of intra-abdominal origin. Gram-negative organisms comprised 43% of blood isolates, followed by gram-positives (33%), anaerobes (14%), and yeast (9%). Appropriate antimicrobial therapy was administered in 71% of patients. The overall mortality rate was 27.8%. As compared with survivors, non-survivors were older, more likely to have underlying COPD or asthma, and have renal or metabolic failure (p<0.05 for all). Among non-survivors, adequate source control was obtained less frequently (64% vs. 91%, p=0.002) and median time to appropriate antibiotics was longer (23 h vs. 4 h, p=0.004). Logistic regression analysis revealed inadequate source control (p=0.002) and inappropriate antibiotics (p=0.016) to be independently associated with mortality. CONCLUSIONS: Critically ill patients with a BSI of abdominal origin are at high risk for mortality. Failure to achieve adequate source control and administration of inappropriate antibiotics were independent predictors of mortality. Thus, these represent potential opportunities to impact outcomes in patients with complicated IAI. PMID- 26258266 TI - 25(th) Anniversary State-of-the-Art Expert Discussion With John J. Meehan, MD, FACS, on Robotics. PMID- 26258264 TI - Bioimaging of Hyaluronate-Interferon alpha Conjugates Using a Non-Interfering Zwitterionic Fluorophore. AB - We conducted real-time bioimaging of the hyaluronate-interferon alpha (HA IFNalpha) conjugate using a biologically inert zwitterionic fluorophore of ZW800 1 for the treatment of hepatitis C virus (HCV) infection. ZW800-1 was labeled on the IFNalpha molecule of the HA-IFNalpha conjugate to investigate its biodistribution and clearance without altering its physicochemical and targeting characteristics. Confocal microscopy clearly visualized the effective in vitro cellular uptake of the HA-IFNalpha conjugate to HepG2 cells. After verifying the biological activity in Daudi cells, we conducted the pharmacokinetic analysis of the HA-IFNalpha conjugate, which confirmed its target-specific delivery to the liver with a prolonged residence time longer than that of PEGylated IFNalpha. In vivo and ex vivo bioimaging of the ZW800-1-labeled HA-IFNalpha conjugate directly showed real-time biodistribution and clearance of the conjugate that are consistent with the biological behaviors analyzed by an enzyme-linked immunosorbent assay. Furthermore, the elevated level of OAS1 mRNA in the liver confirmed in vivo antiviral activity of HA-IFNalpha conjugates. With the data taken together, we could confirm the feasibility of ZW800-1 as a biologically inert fluorophore and target-specific HA-IFNalpha conjugate for the treatment of HCV infection. PMID- 26258267 TI - Transanal Endoscopic Microsurgery After Neoadjuvant Chemoradiotherapy for Rectal Cancer. AB - BACKGROUND: Radical rectal resection following neoadjuvant chemoradiation therapy (CRT) for locally advanced rectal cancer is accompanied by relatively high morbidity. Local excision of rectal cancer may be more appropriate for some frail patients with severe comorbidities. Transanal endoscopic microsurgery (TEM), consisting of local excision of selected rectal cancers, has been associated with low rates of postoperative complications. Because neoadjuvant CRT for rectal cancer may be associated with increased complications, the suitability of TEM following CRT is still unclear. In this study we aimed to assess the clinical outcomes of patients undergoing TEM following neoadjuvant CRT. PATIENTS AND METHODS: This study retrospectively analyzed all patients undergoing TEM for malignant rectal tumor in our institution between 2004 and 2010. They were divided into those who received CRT (CRT group) and those without CRT (non-CRT group). Demographics and clinical data were compared. RESULTS: Forty-four of 97 patients who underwent TEM were included: 13 CRT and 31 non-CRT. Age, comorbidities, and the duration of the procedure were similar for both groups. There were no significant group differences in tumor diameter (2.1 cm [range, 0.5 3.5 cm] and 2.9 cm [range, 0.5-4.2 cm], respectively; P=.125) or distance of the lower part of the tumor from the anal verge (6.7 cm [range, 5-10 cm] and 7.7 cm [range, 5-15 cm], respectively; P=.285). Two non-CRT patients had peritoneal entry, and 1 of them underwent protective ileostomy because of insecure rectal defect closure. One non-CRT patient underwent a re-operation for postoperative bleeding. The other perioperative complications were minor and included urinary retention requiring catheter placement (2 patients in each group), pulmonary edema (1 non-CRT patient), and pneumonia (1 non-CRT patient). All complications were managed conservatively. There was no wound disruption, major complication, or mortality in either group. CONCLUSIONS: With proper patient selection, TEM can be performed safely following CRT, without major complication or increased postoperative morbidity. PMID- 26258268 TI - Laparoendoscopic Single-Site Plus One-Port Donor Nephrectomy: Analysis of 169 Cases. AB - OBJECTIVE: To present our experience with laparoendoscopic single-site plus one port donor nephrectomy (LESSOP-DN) and compare the outcomes with laparoscopic donor nephrectomy (LDN). MATERIALS AND METHODS: Prospectively collected data from 169 consecutive LESSOP-DNs and 83 LDNs performed by a single surgeon in the same time period were analyzed retrospectively. RESULTS: No differences in mean operative time (136 versus 130 minutes; P=.15), warm ischemia time (3.4 versus 3.5 minutes; P=.42), blood loss (50 versus 45 mL; P=.41), transfusion rates (0 versus 1 case), hospital stay (4.0 versus 3.9 days; P=.48), or overall complication rate (12.0% versus 7.7%; P=.25) were observed between the LDN and LESSOP-DN groups. The LESSOP-DN group had a shorter time to return to 100% recovery (39 versus 74 days; P<.001), a smaller surgical incision (5.5 versus 8.2 cm; P<.001), higher scar satisfaction score (8.1 versus 6.4; P=.003), and lower analgesic requirements (79.0 versus 68.5 mg; P=.03) than the LDN group. Renal function of the recipient based on estimated glomerular filtration rate at 1 and 3 months was similar between the groups. Health-related quality of life (QOL) was significantly higher in the LESSOP-DN group in four domains of the health survey than in the LDN group. CONCLUSIONS: LESSOP-DN might be associated with smaller surgical incision, improved cosmetic satisfaction, less time to recovery, less analgesic requirement, improved donor QOL, and equivalent recipient graft function. PMID- 26258269 TI - Early and Midterm Outcome After Laparoscopic Fundoplication and a Minimally Invasive Endoscopic Procedure in Patients with Gastroesophageal Reflux Disease: A Prospective Observational Study. AB - BACKGROUND AND AIMS: Although the minimally invasive endoscopic Stretta procedure is being increasingly used as an alternative strategy to manage gastroesophageal reflux disease (GERD), the benefits of this procedure have to be further evaluated in clinical settings. This prospective observational study assessed the short-term and midterm outcomes associated with laparoscopic Toupet fundoplication (LTF) and the Stretta procedure. PATIENTS AND METHODS: From January 2011 to January 2012, we allocated 80 patients to LTF and 85 to the Stretta procedure. Primary outcome measures, including symptom scores of heartburn, regurgitation, chest pain, belching, hiccup, cough, and asthma, as well as proton pump inhibitor (PPI) use, were analyzed at midterm follow-up (1-3 years). RESULTS: Of the 165 patients, 125 patients following LTF (n=65) or the Stretta procedure (n=60) completed the designated 3-year follow-up and were included in the final analysis. At the end of the 3-year follow-up, the symptom scores were all significantly decreased compared with the corresponding values before the two procedures in both groups (P<.05). After LTF and the Stretta procedure, 47/65 (72.3%) and 41/60 (68.3%) patients, respectively, achieved complete PPI therapy independence (72.3% versus 68.3%, P=.627). Comparing with LTF, however, the Stretta procedure had less effect on improving typical symptoms of heartburn, regurgitation, and chest pain and reducing the rate of re-operation (11.8% versus 0%, P=.006). CONCLUSIONS: LTF and the Stretta procedure were equally effective in controlling GERD symptoms and reducing PPI use. However, LTF can achieve more improvement on typical symptoms and has a lower rate of re operation. PMID- 26258270 TI - The epidemiology and genetics of binge eating disorder (BED). AB - This narrative review provides an overview of the epidemiology of binge eating disorder (BED), highlighting the medical history of this disorder and its entry as an independent condition in the Feeding and Eating Disorders section of the recently published Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Estimates of prevalence are provided, as well as recognition that the female to male ratio is lower in BED than in other eating disorders. Evidence is also provided of the most common comorbidities of BED, including mood and anxiety disorders and a range of addiction disorders. In addition, discussion of the viewpoint that BED itself may be an addiction - at least in severe cases - is presented. Although the genetic study of BED is still in its infancy, current research is reviewed with a focus on certain neurotransmitter genes that regulate brain reward mechanisms. To date, a focal point of this research has been on the dopamine and the MU-opioid receptor genes. Preliminary evidence suggests that a predisposing risk factor for BED may be a heightened sensitivity to reward, which could manifest as a strong dopamine signal in the brain's striatal region. Caution is encouraged, however, in the interpretation of current findings, since samples are relatively small in much of the research. To date, no genome-wide association studies have focused exclusively on BED. PMID- 26258271 TI - Primary refractory diffuse large B cell lymphoma in the rituximab era. AB - PURPOSE OF REVIEW: The aim of this review is to describe the outcome of primary refractory diffuse large B cell lymphoma in the rituximab era and the different therapeutic options as well as new biological markers that could allow the pathologist to distinguish these cases at diagnosis. RECENT FINDINGS: Diffuse large B cell lymphoma outcome has been impressively improved since the introduction of rituximab in association with anthracycline-based chemotherapy; however, primary refractory patients still represent an unmet medical need. SUMMARY: If patients without relapse after 2 years from diagnosis have an outcome comparable to healthy individuals, primary refractory patients still represent 20% of the cases with a very poor overall survival. These cases are usually described as progressive patients during first line or patients reaching a nonadequate partial response or those relapsing within a year after reaching a response. PMID- 26258272 TI - Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly: a concise review and update. AB - PURPOSE OF REVIEW: Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly is an EBV-positive monoclonal large B-cell proliferative disease that arises in elderly patients older than 50 years. Updated knowledge on geographical/ethnical variations in the prevalence and prognostic impact of EBV positivity, the genetic mechanisms of lymphomagenesis, and the validity of the disease is available. RECENT FINDINGS: The poor prognostic impact of EBV positivity is consistent among Asian populations, but not in Western populations. CD30 may be associated with this geographical/ethnical variation. Gene expression analyses have confirmed the enhanced activity of the NF-kappaB and JAK/STAT pathways and more frequent expression of CD30 in EBV-positive DLBCL of the elderly. A substantial proportion of cases of EBV-positive DLBCL of the elderly occur in young immunocompetent adults; moreover, EBV-positive DLBCL in young adults has a distinct clinical course compared with EBV-positive DLBCL of the elderly. SUMMARY: Further research is anticipated, as follows: first, identifying geographical/ethnical differences in gene expression profiles and CD30 coexpression in EBV-positive DLBCL of the elderly; second, feasibility of the revision of the current disease entity confined to elderly patients; and third, novel therapeutic approaches targeting CD30 and the NF-kappaB and JAK/STAT pathways in EBV-positive DLBCL of the elderly. PMID- 26258273 TI - Current status of human papillomavirus vaccination. AB - PURPOSE OF REVIEW: In this article, we review the impact of the quadrivalent and bivalent prophylactic human papillomavirus (HPV) vaccines on HPV infection and disease, review alternative vaccine dosing schedules, the vaccination of men and the nine-valent HPV vaccine. RECENT FINDINGS: HPV vaccines have had dramatic impacts on the prevalence of targeted HPV types (6,11,16 and 18), genital warts and precancerous cervical lesions. Population coverage would be facilitated by adopting two-dose schedules, with recent findings that two-dose schedules in young adolescents are as immunogenic as three doses in young adults. Extension of vaccination to men, particularly for men who have sex with men, could further reduce population prevalence of HPV and provide direct protection to men against genital warts and anal, penile and oropharyngeal cancers. The nine-valent HPV vaccine has demonstrated equivalent protection against the four types in the quadrivalent vaccine and high efficacy against the next five commonest causes of cervical cancer (HPV types 31,33,45,52 and 58). If cost-effective, it may extend the spectrum of protection against cervical cancer available through vaccination. SUMMARY: HPV vaccination is an effective strategy for reducing the burden of HPV related disease. New schedules, target populations and vaccines promise to expand this potential further. PMID- 26258274 TI - The Effects of Vertical Yoked Prism on Horizontal Heterophoria. AB - PURPOSE: Vertical yoked prisms (VYPs) have been recommended for the remediation of vergence dysfunction, but the evidence base for their use is mostly low level. This study investigates the effect of VYP on horizontal subjective dissociated heterophoria. METHODS: Phoria measurement was performed in primary gaze with the Modified Thorington technique at 3 m and at 40 cm on 40 nonpresbyopic young adults. Subjects were seated and head position was held constant. Baseline measures (without yoked prism) of distance and near phoria were measured. Phorias were measured again through the following range of VYP, randomly presented: 2 prism diopters (Delta) base up (BU), 2Delta base down (BD), 5Delta BU, and 5Delta BD. Twenty-six subjects also had their phorias measured with control lenses of +0.125 DS OU (because of unavailability of Plano trial lenses) randomly presented along the other conditions. RESULTS: There was no significant difference overall between phoria measured in any of the yoked prism conditions, including the baseline measure, at distance or near. Neither was there evidence of a predictable esophoric or exophoric shift with either BU or BD prism. CONCLUSIONS: Vertical yoked prisms did not exert any immediate effect on horizontal phoria in young adults when posture was controlled. This suggests that, if VYPs do indeed improve horizontal vergence problems, they do not do so by a direct or immediate impact on horizontal phoria. PMID- 26258275 TI - Improved Photoreceptor Function in Male Acute Zonal Occult Outer Retinopathy. AB - PURPOSE: To describe male acute zonal occult outer retinopathy (AZOOR) patients with improvement of photoreceptor structure and visual function. CASE SERIES: Medical records for eight eyes in seven patients (mean age, 36.9 years; range, 22 to 57 years) with AZOOR were reviewed retrospectively. Of the seven patients, four were treated with high-dose methylprednisolone therapy and three were not treated. All patients presented with photopsias and severe vision loss in the affected eyes. Visual acuity ranged from 0.2 to 1.5 on a Snellen decimal scale and Humphrey visual field testing showed blind spot enlargement or ring scotomas. Fundus and angiographic examinations found no specific abnormalities, leading to a diagnosis of AZOOR. Spectral domain optical coherence tomography showed attenuation of the photoreceptor inner segment ellipsoid zone. Multifocal electroretinography demonstrated that there were decreased responses at the site of the spectral domain optical coherence tomography abnormalities and corresponding visual field loss. Three patients had a spontaneous resolution with restoration of photoreceptor structure and visual function, and four patients had a visual improvement with restoration of photoreceptor structure and visual function after steroid pulse therapy. CONCLUSIONS: These results suggest that male AZOOR patients may have a tendency of visual improvement both with and without treatment. PMID- 26258276 TI - Comparing Autorefractors for Measurement of Accommodation. AB - PURPOSE: To compare the static and dynamic accommodative responses measured with the WAM-5500 and the PowerRef-II autorefractors. METHODS: The dynamic and static monocular accommodative responses were measured with the WAM-5500 and the PowerRef-II instruments in 30 pre-presbyopic patients (23.66 [+/-3.19] years). The spherical equivalent was measured at 0.00, 2.50, and 5.00 diopters (D) of accommodative stimulation for the static measurements. The subjective refraction was also determined. Dynamic accommodation was measured for abrupt changes of stimulus vergence of 2.00 D. Mean and peak velocities of accommodation and disaccommodation were evaluated. For the PowerRef-II, dynamic measurements were calculated for sampling frequencies of 5 and 25 Hz. RESULTS: For far distance static results, the differences between subjective and WAM-5500 measurements were 0.07 (+/-0.21) D (p = 0.093) and those between subjective and PowerRef-II measurements were 0.70 (+/-0.47) D (p = 0.001). The difference in the response measured with both instruments was 0.08 (+/-0.32) D (p = 0.194) for 2.50 D and 0.32 (+/-0.48) D (p = 0.001) for 5.00 D of stimulation. For the dynamic mode, the PowerRef-II at 25 Hz measured faster mean and peak velocities of accommodation and disaccommodation than the WAM-5500, with statistically significant (p < 0.05) differences of 0.68 (+/-1.01), 0.67 (+/-0.98), 1.26 (+/-1.19), and 1.42 (+/-1.53) D/s, respectively. With a sampling frequency of 5 Hz for the PowerRef-II, these differences, which were statistically significant (p < 0.05), were reduced to 0.52 (+/-0.90), 0.49 (+/-0.91), 0.83 (+/-1.07), and 0.83 (+/-1.31) D/s, respectively. CONCLUSIONS: There is good agreement between subjective refraction and WAM-5500 measurements. In contrast, the PowerRef-II produced more hyperopic results. There were no differences among instruments at 2.50 D of static stimulation; however, differences were found at 5.00 D. In the dynamic measurements, the PowerRef-II measured faster velocities, partly attributed to the difference in the sampling frequency. PMID- 26258277 TI - Bilateral Iritis after Vaccine for Bladder Cancer. AB - PURPOSE: Bacille Calmette-Guerin (BCG) is a vaccine that can be instilled into the urinary bladder as immunotherapy against superficial bladder cancer. Several case reports have implicated intravesical BCG in the development of uveitis. Patients treated with BCG therapy may present with systemic symptoms resembling reactive arthritis and, less frequently, have ocular adverse effects including bilateral panuveitis or chorioretinitis. In all but three previously reported cases of uveitis associated with BCG treatment, HLA-B27 has been positive. No patients have been reported to be positive for rheumatoid factor or antinuclear antibody (ANA). CASE REPORT: An HLA-B27-negative and low-positive ANA patient presented with bilateral uveitis after treatment with BCG therapy for superficial bladder cancer. CONCLUSIONS: There is a need for greater awareness among urologists, primary care physicians, and optometrists of the potential for BCG to cause uveitis. These doctors should look for indicators of uveitis, such as circumlimbal conjunctival injection, photophobia, irregular pupils, and keratic precipitates. Together with appropriate treatment or prompt referral, this could prevent unnecessary morbidity. Future studies are needed to further elucidate the possible reasons for ANA positivity in these patients and the future role of the test in diagnosis and management. PMID- 26258278 TI - Subconjunctival Herniated Orbital Fat Mimicking Adipocytic Neoplasm. AB - PURPOSE: To describe and discuss rare and benign conditions of subconjunctival orbital fat herniation that may mimic adipocytic neoplasm. METHODS: Sixteen eyes of 13 patients with subconjunctival orbital fat herniation were included. They all underwent transconjunctival excision owing to cosmesis, discomfort, or suspicion of malignancy. Histopathologic examination, postoperative complications, and recurrent conditions were analyzed. RESULTS: Eleven male and two female patients were included. The lesion was unilateral in 10 and bilateral in 3 cases. Excision was performed via conjunctival wound and removing the prolapsed orbital fat. The conjunctiva was then closed with two to three interrupted sutures. All the histopathologic specimens revealed Lochkern cells, floret cells, and mature adipocytes separated by fibrovascular septae without hyperchromatic cells, consistent with subconjunctival herniated orbital fat. All the patients were treated successfully with transconjunctival excision without recurrence at an average follow-up of 10.6 months (range, 6 to 16 months). CONCLUSIONS: Prolapse of subconjunctival orbital fat is an uncommon entity of intraorbital masses and may mimic adipocytic neoplasm. It is usually associated with a dehiscence in the Tenon capsule. Surgical excision is indicated and pathologic evaluation is necessary if any malignancy is suspected. PMID- 26258279 TI - Refractive Changes in Amblyopic Children with High Anisometropia. AB - PURPOSE: To demonstrate the refractive changes of amblyopic children attributed to high anisometropia in the myopia endemic in Taiwan. METHODS: Amblyopic children younger than 10 years with myopic or hyperopic anisometropia 3 diopters (D) or more who had follow-up for more than 2 years and had final visual acuity of 20/30 or better in the amblyopic eye were included. RESULTS: The average age on the first visit was similar for the 13 myopic children (5.5 years) and 17 hyperopic children (5.3 years). Initially, the mean anisometropia was significantly different (myopic, 7.25 D vs. hyperopic, 3.89 D), but the visual acuity of the amblyopic eye (logarithm of the minimum angle of resolution) was similar between both groups at baseline (0.50 vs. 0.57). Myopization of the sound eye surpassed that of the amblyopic eye in the myopic group, which resulted in a yearly reduction of anisometropia of 0.51 D. However, hyperopia decreased synchronously in both eyes of the hyperopic children. The final degree of anisometropia was not significantly different between the two groups (4.07 D vs. 3.62 D). CONCLUSIONS: Growing up in a country with a high prevalence of myopia, children with myopic and hyperopic anisometropia in this study inevitably had myopization in both eyes. Myopic anisometropia decreases significantly over time, but hyperopic anisometropia remains constant. PMID- 26258280 TI - Effect of Corneal Thickness on the Penetration of Topical Vancomycin. AB - PURPOSE: To study the influence of corneal thickness on intraocular penetration of topical ophthalmic drops, using vancomycin 50 mg/mL drops as a model. METHODS: The study included 58 eyes of 58 patients undergoing phacoemulsification cataract extraction. The central corneal thickness was measured by ultrasonic pachymetry on the day of surgery. Thirty minutes before the surgery, one drop of topical vancomycin 50 mg/mL was instilled three times with 10-minute intervals: 30 minutes, 20 minutes, and 10 minutes before the surgery. At the beginning of surgery, a small specimen of aqueous humor was aspirated and sent to the laboratory for measurement of drug concentration to determine the effect of corneal thickness on vancomycin concentration in the anterior chamber. RESULTS: There was insufficient amount of aqueous humor for analysis in 9 samples, leaving a total of 49 samples. The mean central corneal thickness was 539.7 (+/-39.5) MUm (range, 458 to 635 MUm). The mean vancomycin concentration in the anterior chamber was 0.220 (+/-0.209) MUg/mL. There was no significant association between vancomycin concentration and corneal thickness (r = -0.07, p = 0.62, Pearson correlation). When patients were divided into three groups based on the mean (+/ 1 SD) central corneal thickness, no significant differences in vancomycin concentrations (in micrograms per milliliter) were encountered: 0.267 (+/-0.247) (for corneal thickness <500.2 MUm), 0.209 (+/-0.212) (for corneal thickness of 500.2 to 579.2 MUm), and 0.200 (+/-0.160) (for corneal thickness >579.2 MUm) (p = 0.73, analysis of variance). CONCLUSIONS: Corneal thickness does not influence the penetration of topically applied vancomycin into the anterior chamber. PMID- 26258281 TI - Bridging the Gap: Electron Relay and Plasmonic Sensitization of Metal Nanocrystals for Metal Clusters. AB - In recent years, enormous attention has been paid to the construction of metal cluster-semiconductor nanocomposites because of the fascinating and unique properties of metal clusters; however, investigations on photoelectrochemical (PEC) and photocatalytic properties of metal cluster-semiconductor systems are still rare. Moreover, to date, intrinsic correlation between metal clusters and bulk metal nanocrystals has yet to be elucidated. In this work, a facile layer-by layer (LbL) self-assembly strategy has been developed to judiciously and intimately integrate gold nanocrystals (Au) within the interface between gold clusters (Au(x)) and hierarchically ordered TiO2 nanotube arrays framework, by which imperative roles of Au nanocrystals as electron relay mediator and plasmonic sensitizer for Aux clusters were revealed. In addition, it was found that synergistic interaction between Au nanocrystals and Aux clusters contributed to promising visible-light-driven photocatalytical and PEC performances. It is anticipated that our work could provide a general way for rationally constructing metal and metal clusters codecorated semiconductor heterostructures and, more significantly, bridge the gap between metal clusters and metal nanocrystals for a diverse range of applications. PMID- 26258282 TI - High diversity stabilizes the thermal resilience of pollinator communities in intensively managed grasslands. AB - The resilience of ecosystems depends on the diversity of species and their specific responses to environmental variation. Here we show that the diversity of climatic responses across species contributes to a higher projected resilience of species-rich pollinator communities in real-world ecosystems despite land-use intensification. We determined the thermal niche of 511 pollinator species (flies, bees, beetles and butterflies) in 40 grasslands. Species in intensively used grasslands have broader thermal niches and are also more complementary in their thermal optima. The observed increase in thermal resilience with land-use intensification is mainly driven by the dominant flies that prefer cooler temperatures and compensate for losses of other taxa. Temperature explained 84% of the variation in pollinator activity across species and sites. Given the key role of temperature, quantifying the diversity of thermal responses within functional groups is a promising approach to assess the vulnerability of ecosystems to land-use intensification and climate change. PMID- 26258283 TI - Defective DNA repair and increased chromatin binding of DNA repair factors in Down syndrome fibroblasts. AB - Down syndrome (DS) is characterized by genetic instability, neurodegeneration, and premature aging. However, the molecular mechanisms leading to this phenotype are not yet well understood. Here, we report that DS fibroblasts from both fetal and adult donors show the presence of oxidative DNA base damage, such as dihydro 8-oxoguanine (8-oxodG), and activation of a DNA damage response (DDR), already during unperturbed growth conditions. DDR with checkpoint activation was indicated by histone H2AX and Chk2 protein phosphorylation, and by increased p53 protein levels. In addition, both fetal and adult DS fibroblasts were more sensitive to oxidative DNA damage induced by potassium bromate, and were defective in the removal of 8-oxodG, as compared with age-matched cells from control healthy donors. The analysis of core proteins participating in base excision repair (BER), such as XRCC1 and DNA polymerase beta, showed that higher amounts of these factors were bound to chromatin in DS than in control cells, even in the absence of DNA damage. These findings occurred in concomitance with increased levels of phosphorylated XRCC1 detected in DS cells. These results indicate that DS cells exhibit a BER deficiency, which is associated with prolonged chromatin association of core BER factors. PMID- 26258284 TI - Incidence Rate and Risk Factors for Contralateral Eye Involvement among Patients with AIDS and Cytomegalovirus Retinitis Treated with Local Therapy. AB - PURPOSE: To calculate the incidence of, and to identify the risk factors for developing contralateral eye involvement among patients with AIDS and unilateral cytomegalovirus retinitis (CMV retinitis), who were treated, in the era of highly active antiretroviral therapy (HAART), with repetitive intravitreal ganciclovir injections. MATERIALS AND METHODS: The clinical records of 119 patients were included. The main outcome measurement was the occurrence of contralateral eye involvement. RESULTS: Over a mean follow-up period of 1.6 years, the overall incidence rate of contralateral involvement was 0.17/person-year. The cumulative incidence of contralateral involvement at 6 months and 1 year was 23.8% and 28.4%, respectively. Receiving HAART at the visit before the event was associated with a decreased risk of developing contralateral retinitis (hazard ratio [HR] = 0.26, P = 0.002). CONCLUSIONS: The use of HAART, associated with subsequent immune recovery, significantly reduced the incidence of contralateral eye involvement by approximately 75% among patients in our setting. PMID- 26258285 TI - Angel's share combats wine fraud: (14)C dating of wine without opening the bottle. AB - The problem of fraud continues to plague the wine industry, and detecting cases where the original bottle has been refilled with an inferior vintage is especially difficult. A novel noninvasive procedure presented here relies on radiocarbon dating the so-called angel's share: the trace amounts of ethanol and other gases that diffuse into and through the cork as bottled wine ages and matures. These are collected by applying a vacuum to the top of the bottle and cryo-trapping the extracted gas, leaving the liquid contents untouched. Vintage verification is therefore possible without exposing the liquid contents to the atmosphere, which may render a bottle costing tens of thousands of dollars worthless for later resale and consumption. The method also has a potential for stable isotope ratio as well as chemical analysis to find indications for fraud or spoilage of fine and rare wines as well as other liquids with cork stoppers. PMID- 26258287 TI - Resistant Catatonia in a High-Functioning Autism Spectrum Disorder Patient Successfully Treated with Amantadine. PMID- 26258286 TI - Two enzymes with redundant fructose bisphosphatase activity sustain gluconeogenesis and virulence in Mycobacterium tuberculosis. AB - The human pathogen Mycobacterium tuberculosis (Mtb) likely utilizes host fatty acids as a carbon source during infection. Gluconeogenesis is essential for the conversion of fatty acids into biomass. A rate-limiting step in gluconeogenesis is the conversion of fructose 1,6-bisphosphate to fructose 6-phosphate by a fructose bisphosphatase (FBPase). The Mtb genome contains only one annotated FBPase gene, glpX. Here we show that, unexpectedly, an Mtb mutant lacking GLPX grows on gluconeogenic carbon sources and has detectable FBPase activity. We demonstrate that the Mtb genome encodes an alternative FBPase (GPM2, Rv3214) that can maintain gluconeogenesis in the absence of GLPX. Consequently, deletion of both GLPX and GPM2 is required for disruption of gluconeogenesis and attenuation of Mtb in a mouse model of infection. Our work affirms a role for gluconeogenesis in Mtb virulence and reveals previously unidentified metabolic redundancy at the FBPase-catalysed reaction step of the pathway. PMID- 26258288 TI - Vascular emergencies: Diagnosis and treatment. PMID- 26258289 TI - Implementation of the Integrated Electronic Patient Portal in the Pediatric Population: A Systematic Review. AB - BACKGROUND: This study assessed the current state of knowledge regarding the use of the integrated electronic health record (EHR) patient portal for pediatric clinical care. A systematic examination of the research on implementation, utilization, and evaluation of the integrated EHR patient portal among pediatric patients has not been previously conducted. Therefore, the purpose of the present study was to systematically review existing research on the state of the science, describe the way others have defined the patient portal, and examine pediatric patient portal utilization. MATERIALS AND METHODS: Covering a period from 1992 to 2014 a literature search was conducted on four electronic databases. Only articles in English were reviewed. Studies were included if they reported the use of a patient portal integrated with an electronic health record and captured pediatric medial encounters. Qualitative or quantitative studies of any design were eligible as long as they focused on patients (or parents) who access their health records through an electronic portal tied to an EHR and reported measures of satisfaction, attitudes on use, barriers and facilitators, adherence, or clinical and health outcomes. Content analysis of each article was performed independently by at least two authors using an extraction grid of study qualities, and quality and relevance of the studies were also assessed. RESULTS: Of a total of 189 potentially relevant publications identified, 31 full-text publications were obtained after screening titles and abstracts. After a full review, 11 publications corresponding to seven studies met the inclusion criteria. The methodological approaches included cross-sectional surveys, retrospective analysis, qualitative studies, and usability testing. In general, feedback was positive. The most frequent negative comments about the portal reflected concern about teenager interaction with the portal and how that might affect communication among patient, parent, and provider. Some users were frustrated with the complexity of medical terminology used. CONCLUSIONS: Reflecting the additional considerations of pediatric proxy access and fewer chronically ill patients, pediatric medicine has yet to use the patient portal as a modality for outcomes measurement. Given the paucity of studies within this age group, it is difficult to measure outcome improvements or the effect of patient record access on healthcare behaviors. This systematic review presents innovative research on the general acceptance of the patient portal among parents and highlights that the implementation of the portal is still in its early stages and has yet to be used widely in diverse populations or studies in a longitudinal manner. Further studies should confirm that protected access to health information and secure communication and information sharing with healthcare providers have an impact in the pediatric population on healthcare outcomes. PMID- 26258290 TI - Engraved Suicide Notes: The Last Note Written on Body by Metallic Object. AB - "Suicide notes" are the notes, where the victim has documented the intention to terminate one's own life. The victim generally writes them on a paper, notebook, wall, or mirror by means of pen or marker. However, suicide notes written on one's own body are very rare, and suicide note engraved by some metallic objects over body has not yet reported. We present two cases where the victim had used some metallic objects to write a message on the body. These may be termed "engraved suicide notes." We believe these to be the first reported cases where a metallic object was used for engraving the last notes on the body before committing suicide. PMID- 26258291 TI - SpeedSeq: ultra-fast personal genome analysis and interpretation. AB - SpeedSeq is an open-source genome analysis platform that accomplishes alignment, variant detection and functional annotation of a 50* human genome in 13 h on a low-cost server and alleviates a bioinformatics bottleneck that typically demands weeks of computation with extensive hands-on expert involvement. SpeedSeq offers performance competitive with or superior to current methods for detecting germline and somatic single-nucleotide variants, structural variants, insertions and deletions, and it includes novel functionality for streamlined interpretation. PMID- 26258292 TI - High-throughput cellular RNA device engineering. AB - Methods for rapidly assessing sequence-structure-function landscapes and developing conditional gene-regulatory devices are critical to our ability to manipulate and interface with biology. We describe a framework for engineering RNA devices from preexisting aptamers that exhibit ligand-responsive ribozyme tertiary interactions. Our methodology utilizes cell sorting, high-throughput sequencing and statistical data analyses to enable parallel measurements of the activities of hundreds of thousands of sequences from RNA device libraries in the absence and presence of ligands. Our tertiary-interaction RNA devices performed better in terms of gene silencing, activation ratio and ligand sensitivity than optimized RNA devices that rely on secondary-structure changes. We applied our method to build biosensors for diverse ligands and determine consensus sequences that enable ligand-responsive tertiary interactions. These methods advance our ability to develop broadly applicable genetic tools and to elucidate the underlying sequence-structure-function relationships that empower rational design of complex biomolecules. PMID- 26258293 TI - Continuous directed evolution of DNA-binding proteins to improve TALEN specificity. AB - Nucleases containing programmable DNA-binding domains can alter the genomes of model organisms and have the potential to become human therapeutics. Here we present DNA-binding phage-assisted continuous evolution (DB-PACE) as a general approach for the laboratory evolution of DNA-binding activity and specificity. We used this system to generate transcription activator-like effectors nucleases (TALENs) with broadly improved DNA cleavage specificity, establishing DB-PACE as a versatile approach for improving the accuracy of genome-editing agents. PMID- 26258295 TI - Conformational dynamics of a class C G-protein-coupled receptor. AB - G-protein-coupled receptors (GPCRs) constitute the largest family of membrane receptors in eukaryotes. Crystal structures have provided insight into GPCR interactions with ligands and G proteins, but our understanding of the conformational dynamics of activation is incomplete. Metabotropic glutamate receptors (mGluRs) are dimeric class C GPCRs that modulate neuronal excitability, synaptic plasticity, and serve as drug targets for neurological disorders. A 'clamshell' ligand-binding domain (LBD), which contains the ligand-binding site, is coupled to the transmembrane domain via a cysteine-rich domain, and LBD closure seems to be the first step in activation. Crystal structures of isolated mGluR LBD dimers led to the suggestion that activation also involves a reorientation of the dimer interface from a 'relaxed' to an 'active' state, but the relationship between ligand binding, LBD closure and dimer interface rearrangement in activation remains unclear. Here we use single-molecule fluorescence resonance energy transfer to probe the activation mechanism of full length mammalian group II mGluRs. We show that the LBDs interconvert between three conformations: resting, activated and a short-lived intermediate state. Orthosteric agonists induce transitions between these conformational states, with efficacy determined by occupancy of the active conformation. Unlike mGluR2, mGluR3 displays basal dynamics, which are Ca(2+)-dependent and lead to basal protein activation. Our results support a general mechanism for the activation of mGluRs in which agonist binding induces closure of the LBDs, followed by dimer interface reorientation. Our experimental strategy should be widely applicable to study conformational dynamics in GPCRs and other membrane proteins. PMID- 26258298 TI - The pre-vertebrate origins of neurogenic placodes. AB - The sudden appearance of the neural crest and neurogenic placodes in early branching vertebrates has puzzled biologists for over a century. These embryonic tissues contribute to the development of the cranium and associated sensory organs, which were crucial for the evolution of the vertebrate "new head". A previous study suggests that rudimentary neural crest cells existed in ancestral chordates. However, the evolutionary origins of neurogenic placodes have remained obscure owing to a paucity of embryonic data from tunicates, the closest living relatives to those early vertebrates. Here we show that the tunicate Ciona intestinalis exhibits a proto-placodal ectoderm (PPE) that requires inhibition of bone morphogenetic protein (BMP) and expresses the key regulatory determinant Six1/2 and its co-factor Eya, a developmental process conserved across vertebrates. The Ciona PPE is shown to produce ciliated neurons that express genes for gonadotropin-releasing hormone (GnRH), a G-protein-coupled receptor for relaxin-3 (RXFP3) and a functional cyclic nucleotide-gated channel (CNGA), which suggests dual chemosensory and neurosecretory activities. These observations provide evidence that Ciona has a neurogenic proto-placode, which forms neurons that appear to be related to those derived from the olfactory placode and hypothalamic neurons of vertebrates. We discuss the possibility that the PPE derived GnRH neurons of Ciona resemble an ancestral cell type, a progenitor to the complex neuronal circuit that integrates sensory information and neuroendocrine functions in vertebrates. PMID- 26258299 TI - The zinc transporter ZIP12 regulates the pulmonary vascular response to chronic hypoxia. AB - The typical response of the adult mammalian pulmonary circulation to a low oxygen environment is vasoconstriction and structural remodelling of pulmonary arterioles, leading to chronic elevation of pulmonary artery pressure (pulmonary hypertension) and right ventricular hypertrophy. Some mammals, however, exhibit genetic resistance to hypoxia-induced pulmonary hypertension. We used a congenic breeding program and comparative genomics to exploit this variation in the rat and identified the gene Slc39a12 as a major regulator of hypoxia-induced pulmonary vascular remodelling. Slc39a12 encodes the zinc transporter ZIP12. Here we report that ZIP12 expression is increased in many cell types, including endothelial, smooth muscle and interstitial cells, in the remodelled pulmonary arterioles of rats, cows and humans susceptible to hypoxia-induced pulmonary hypertension. We show that ZIP12 expression in pulmonary vascular smooth muscle cells is hypoxia dependent and that targeted inhibition of ZIP12 inhibits the rise in intracellular labile zinc in hypoxia-exposed pulmonary vascular smooth muscle cells and their proliferation in culture. We demonstrate that genetic disruption of ZIP12 expression attenuates the development of pulmonary hypertension in rats housed in a hypoxic atmosphere. This new and unexpected insight into the fundamental role of a zinc transporter in mammalian pulmonary vascular homeostasis suggests a new drug target for the pharmacological management of pulmonary hypertension. PMID- 26258303 TI - Measurement-based control of a mechanical oscillator at its thermal decoherence rate. AB - In real-time quantum feedback protocols, the record of a continuous measurement is used to stabilize a desired quantum state. Recent years have seen successful applications of these protocols in a variety of well-isolated micro-systems, including microwave photons and superconducting qubits. However, stabilizing the quantum state of a tangibly massive object, such as a mechanical oscillator, remains very challenging: the main obstacle is environmental decoherence, which places stringent requirements on the timescale in which the state must be measured. Here we describe a position sensor that is capable of resolving the zero-point motion of a solid-state, 4.3-megahertz nanomechanical oscillator in the timescale of its thermal decoherence, a basic requirement for real-time (Markovian) quantum feedback control tasks, such as ground-state preparation. The sensor is based on evanescent optomechanical coupling to a high-Q microcavity, and achieves an imprecision four orders of magnitude below that at the standard quantum limit for a weak continuous position measurement--a 100-fold improvement over previous reports--while maintaining an imprecision-back-action product that is within a factor of five of the Heisenberg uncertainty limit. As a demonstration of its utility, we use the measurement as an error signal with which to feedback cool the oscillator. Using radiation pressure as an actuator, the oscillator is cold damped with high efficiency: from a cryogenic-bath temperature of 4.4 kelvin to an effective value of 1.1 +/- 0.1 millikelvin, corresponding to a mean phonon number of 5.3 +/- 0.6 (that is, a ground-state probability of 16 per cent). Our results set a new benchmark for the performance of a linear position sensor, and signal the emergence of mechanical oscillators as practical subjects for measurement-based quantum control. PMID- 26258302 TI - Mutations in DCHS1 cause mitral valve prolapse. AB - Mitral valve prolapse (MVP) is a common cardiac valve disease that affects nearly 1 in 40 individuals. It can manifest as mitral regurgitation and is the leading indication for mitral valve surgery. Despite a clear heritable component, the genetic aetiology leading to non-syndromic MVP has remained elusive. Four affected individuals from a large multigenerational family segregating non syndromic MVP underwent capture sequencing of the linked interval on chromosome 11. We report a missense mutation in the DCHS1 gene, the human homologue of the Drosophila cell polarity gene dachsous (ds), that segregates with MVP in the family. Morpholino knockdown of the zebrafish homologue dachsous1b resulted in a cardiac atrioventricular canal defect that could be rescued by wild-type human DCHS1, but not by DCHS1 messenger RNA with the familial mutation. Further genetic studies identified two additional families in which a second deleterious DCHS1 mutation segregates with MVP. Both DCHS1 mutations reduce protein stability as demonstrated in zebrafish, cultured cells and, notably, in mitral valve interstitial cells (MVICs) obtained during mitral valve repair surgery of a proband. Dchs1(+/-) mice had prolapse of thickened mitral leaflets, which could be traced back to developmental errors in valve morphogenesis. DCHS1 deficiency in MVP patient MVICs, as well as in Dchs1(+/-) mouse MVICs, result in altered migration and cellular patterning, supporting these processes as aetiological underpinnings for the disease. Understanding the role of DCHS1 in mitral valve development and MVP pathogenesis holds potential for therapeutic insights for this very common disease. PMID- 26258306 TI - Corrigendum: Bipolar seesaw control on last interglacial sea level. PMID- 26258305 TI - Structural basis of JAZ repression of MYC transcription factors in jasmonate signalling. AB - The plant hormone jasmonate plays crucial roles in regulating plant responses to herbivorous insects and microbial pathogens and is an important regulator of plant growth and development. Key mediators of jasmonate signalling include MYC transcription factors, which are repressed by jasmonate ZIM-domain (JAZ) transcriptional repressors in the resting state. In the presence of active jasmonate, JAZ proteins function as jasmonate co-receptors by forming a hormone dependent complex with COI1, the F-box subunit of an SCF-type ubiquitin E3 ligase. The hormone-dependent formation of the COI1-JAZ co-receptor complex leads to ubiquitination and proteasome-dependent degradation of JAZ repressors and release of MYC proteins from transcriptional repression. The mechanism by which JAZ proteins repress MYC transcription factors and how JAZ proteins switch between the repressor function in the absence of hormone and the co-receptor function in the presence of hormone remain enigmatic. Here we show that Arabidopsis MYC3 undergoes pronounced conformational changes when bound to the conserved Jas motif of the JAZ9 repressor. The Jas motif, previously shown to bind to hormone as a partly unwound helix, forms a complete alpha-helix that displaces the amino (N)-terminal helix of MYC3 and becomes an integral part of the MYC N-terminal fold. In this position, the Jas helix competitively inhibits MYC3 interaction with the MED25 subunit of the transcriptional Mediator complex. Our structural and functional studies elucidate a dynamic molecular switch mechanism that governs the repression and activation of a major plant hormone pathway. PMID- 26258308 TI - Linking phenotypes and modes of action through high-content screen fingerprints. AB - High-content screening (HCS) is a powerful technique for monitoring phenotypic responses to treatments on a cellular and subcellular level. Cellular phenotypes can be characterized by multivariate image readouts such as shape, intensity, or texture. The corresponding feature vectors can thus be defined as HCS fingerprints that serve as a powerful biological compound descriptor. Therefore, clustering or classification of HCS fingerprints across compound treatments allows for the identification of similarities in protein targets or pathways. We developed an HCS-based profiling panel that serves as basis for characterizing the mode of action of compounds. This panel measures phenotypic effects in six different compartments of U-2OS cells, namely the nucleus, the cytoplasm, the endoplasmic reticulum, the Golgi apparatus, and the cytoskeleton. We profiled a set of 2,725 well-annotated compounds and clustered their corresponding HCS fingerprints to establish links between predominant cellular phenotypes and cellular processes and protein targets. We found various different clusters enriched for individual targets (e.g., HDAC, HSP90, TOP1, HMGCR, TUB), signaling pathways (e.g., PIK3/AKT/mTOR), or gene sets associated with diseases (e.g., psoriasis, leukemia). Based on this clustering we were able to identify novel compound-target associations for selected compounds such as a submicromolar inhibitory activity of Silmitasertib (a casein kinase inhibitor) on PI3K and mTOR. PMID- 26258309 TI - What happened to surgical leadership? PMID- 26258310 TI - Combined preoperative mechanical bowel preparation with oral antibiotics significantly reduces surgical site infection, anastomotic leak, and ileus after colorectal surgery. AB - OBJECTIVES: To clarify whether bowel preparation use or its individual components [mechanical bowel preparation (MBP)/oral antibiotics] impact specific outcomes after colorectal surgery. METHODS: National Surgical Quality Improvement Program targeted colectomy data initiated in 2012 capture information on the use/type of bowel preparation and colorectal-specific complications. For patients undergoing elective colorectal resection, the impact of preoperative MBP and antibiotics (MBP+/ABX+), MBP alone (MBP+/ABX-), and no bowel preparation (no-prep) on outcomes, particularly anastomotic leak, surgical site infection (SSI), and ileus, were evaluated using unadjusted/adjusted logistic regression analysis. RESULTS: Of 8442 patients, 2296 (27.2%) had no-prep, 3822 (45.3%) MBP+/ABX-, and 2324 (27.5%) MBP+/ABX+. Baseline characteristics were similar; however, there were marginally more patients with prior sepsis, ascites, steroid use, bleeding disorders, and disseminated cancer in no-prep. MBP with or without antibiotics was associated with reduced ileus [MBP+/ABX+: odds ratio (OR) = 0.57, 95% confidence interval (CI): 0.48-0.68; MBP+/ABX-: OR = 0.78, 95% CI: 0.68-0.91] and SSI [MBP+/ABX+: OR = 0.39, 95% CI: 0.32-0.48; MBP+/ABX-: OR = 0.80, 95% CI: 0.69 0.93] versus no-prep. MBP+/ABX+ was also associated with lower anastomotic leak rate than no-prep [OR = 0.45 (95% CI: 0.32-0.64)]. On multivariable analysis, MBP with antibiotics, but not without, was independently associated with reduced anastomotic leak (OR = 0.57, 95% CI: 0.35-0.94), SSI (OR = 0.40, 95% CI: 0.31 0.53), and postoperative ileus (OR = 0.71, 95% CI: 0.56-0.90). CONCLUSIONS: These data clarify the near 50-year debate whether bowel preparation improves outcomes after colorectal resection. MBP with oral antibiotics reduces by nearly half, SSI, anastomotic leak, and ileus, the most common and troublesome complications after colorectal surgery. PMID- 26258311 TI - Transfusion of cryopreserved packed red blood cells is safe and effective after trauma: a prospective randomized trial. AB - OBJECTIVES: To determine the safety and efficacy of cryopreserved packed red blood cell (CPRBC) transfusion in trauma patients. BACKGROUND: Liquid packed red blood cells (LPRBCs) have an abbreviated shelf-life and worsening storage lesion with age. CPRBCs are frozen 2 to 6 days after donation, stored up to 10 years, and are available for 14 days after thawing and washing. CPRBCs can be utilized in diverse settings, but the effect on clinical outcomes is unknown. METHODS: We performed a prospective, randomized, double-blind study at 5 level 1 trauma centers. Stable trauma patients requiring transfusion were randomized to young LPRBCs (<=14 storage days), old LPRBCs (>14 storage days), or CPRBCs. Tissue oxygenation (StO2), biochemical and inflammatory mediators were measured, and clinical outcomes were determined. RESULTS: Two hundred fifty-six patients with well-matched injury severity and demographics (P > 0.2) were randomized (84 young, 86 old, and 86 CPRBCs). Pretransfusion and final hematocrits were similar (P > 0.68). Patients in all groups received the same number of units postrandomization (2 [1-4]; P > 0.05). There was no difference in the change in tissue oxygenation between groups. CPRBCs contained less alpha2-macrogobulin, haptoglobin, C-reactive protein, and serum amyloid P (P < 0.001). Organ failure, infection rate, and mortality did not differ between groups (P > 0.2). CONCLUSIONS: Transfusion of CPRBCs is as safe and effective as transfusion of young and old LPRBCs and provides a mechanism to deliver PRBCs in a wide variety of settings. PMID- 26258312 TI - Changing paradigms in the management of 2184 patients with traumatic brain injury. AB - OBJECTIVES: The aim of this study was to assess the change in trends in the management of traumatic brain injury (TBI) at a level I trauma center and the utilization of resources as a result of this change in management. BACKGROUND: The management of TBI has been evolving with trends toward management of minimally injured patients with intracranial hemorrhage exclusively by trauma surgeons. METHODS: A 5-year (2009-2014) prospective database on all patients with TBI (skull fracture/intracranial hemorrhage on head computed tomography) presenting to a level I trauma center was analyzed for patient demographics, injuries, admission physiology, computed tomographic scan results, and hospital outcomes. These records were matched to the institutional registry and hospital financial database. RESULTS: A total of 2184 patients were included with median (interquartile range) Glasgow Coma Scale score of 15 (12-15), and median (interquartile range) head-abbreviated injury scale score of 3 (2-4). The distribution of types and size of intracranial bleeds remained unchanged throughout the study period. The proportion of TBI managed exclusively by trauma surgeons increased significantly over the years from 6.8% to 40.1% (P < 0.001). Proportion of patients who received neurosurgical consultations (P < 0.001) and repeat head computed tomographic scans (P < 0.001), hospital length of stay (P = 0.028), and costs (P < 0.001) decreased significantly over time. The overall mortality rate (18.5%) and rate of intervention (14.1%) remained unchanged. CONCLUSIONS: TBI patients can be selectively managed without initially involving neurosurgeons safely in a cost-effective manner, resulting in more effective use of precious resources. PMID- 26258313 TI - Factors influencing the decision of surgery residency graduates to pursue general surgery practice versus fellowship. AB - OBJECTIVES: Surgery residency serves 2 purposes-prepare graduates for general surgery (GS) practice or postresidency surgical fellowship, leading to specialty surgical practice (SS). This study was undertaken to elucidate factors influencing career choice for these 2 groups. METHODS: All US allopathic surgery residency graduates from 2009 to 2013 (n = 5512) were surveyed by the American Board of Surgery regarding confidence, autonomy, and reasons for career selection between GS and SS. Surveys were distributed by mail in November 2013, with follow up mailings to initial nonrespondents. RESULTS: Sixty-one percent (3354) of graduates completed the survey; 26% pursued GS, and 74% SS. GS expressed greater levels of confidence than SS across the common surgical procedures queried. Confidence increased with each year after completion of residency for GS but not SS. The decision to pursue GS or SS was made during residency by 77% and 74%, respectively. Fifty-seven percent of those who chose GS indicated that a GS mentor significantly influenced their decision. GS rated procedural variety, opportunity for practice autonomy, choice of practice location, and influence of a mentor as reasons to pursue GS practice. SS listed control over scope of practice, prestige, salary, and specialty interest as reasons to pursue SF. Both groups expressed a high degree of satisfaction with their career choice (GS, 94%; SS, 90%). CONCLUSIONS: Most graduates who pursue GS practice are confident and content. The decision to pursue GS is strongly influenced by a GS mentor. Lack of confidence may be a more significant factor for choosing SS. These findings suggest opportunities for improvements in confidence and mentorship during residency. PMID- 26258314 TI - Long-term outcomes of helper peptide vaccination for metastatic melanoma. AB - OBJECTIVE: The objective of this study was to compare the long-term outcome of patients with metastatic melanoma vaccinated with 6MHP to that of a group of unvaccinated historical controls. BACKGROUND: A multipeptide vaccine (6MHP), designed to induce helper T cells against melanocytic and cancer-testis antigens, has been shown to induce specific Th1-dominant CD4+ T cell responses. METHODS: The 6MHP vaccine was administered to patients with metastatic melanoma. Circulating CD4+ T cell responses were measured by proliferation or direct IFN gamma ELIspot assay. Overall survival of vaccinated patients was compared to a group of clinically comparable historical controls using multivariable Cox regression analysis and Kaplan-Meier survival analysis, taking into account age, metastatic site, and resection status. RESULTS: Across 40 vaccinated patients and 87 controls, resection status (HR 0.54, P = 0.004) and vaccination (HR 0.24, P < 0.001) were associated with improved overall survival. Forty pairs of vaccinated patients and controls were matched by metastatic site, resection status, and age within 10 years. Median survival was significantly longer for vaccinated patients (5.4 vs 1.3 years, P < 0.001). Among the vaccinated patients, the development of a specific immune response after vaccination was associated with improved survival (HR 0.35, P = 0.040). CONCLUSIONS: Helper peptide vaccination is associated with improved overall survival among patients with metastatic melanoma. These data support a randomized prospective trial of the 6MHP vaccine. PMID- 26258315 TI - Defining long-term outcomes with living donor liver transplantation in North America. AB - OBJECTIVES: To compare long-term survival of living donor liver transplant (LDLT) at experienced transplant centers with outcomes of deceased donor liver transplant and identify key variables impacting patient and graft survival. BACKGROUND: The Adult-to-Adult Living Donor Liver Transplantation Cohort Study is a prospective multicenter National Institutes of Health study comparing outcomes of LDLT and deceased donor liver transplant and associated risks. METHODS: Mortality and graft failure for 1427 liver recipients (963 LDLT) enrolled in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study who received transplant between January 1, 1998, and January 31, 2014, at 12 North American centers with median follow-up 6.7 years were analyzed using Kaplan-Meier and multivariable Cox models. RESULTS: Survival probability at 10 years was 70% for LDLT and 64% for deceased donor liver transplant. Unadjusted survival was higher with LDLT (hazard ratio = 0.76, P = 0.02) but attenuated after adjustment (hazard ratio = 0.98, P = 0.90) as LDLT recipients had lower mean model for end-stage liver disease (15.5 vs 20.4) and fewer received transplant from intensive care unit, were inpatient, on dialysis, were ventilated, or with ascites. Posttransplant intensive care unit days were less for LDLT recipients. For all recipients, female sex and primary sclerosing cholangitis were associated with improved survival, whereas dialysis and older recipient/donor age were associated with worse survival. Higher model for end-stage liver disease score was associated with increased graft failure. Era of transplantation and type of donated lobe did not impact survival in LDLT. CONCLUSIONS: LDLT provides significant long-term transplant benefit, resulting in transplantation at a lower model for end-stage liver disease score, decreased death on waitlist, and excellent posttransplant outcomes. Recipient diagnosis, disease severity, renal failure, and ages of recipient and donor should be considered in decision making regarding timing of transplant and donor options.Clinical Trials ID: NCT00096733. PMID- 26258316 TI - Resection margin and survival in 2368 patients undergoing hepatic resection for metastatic colorectal cancer: surgical technique or biologic surrogate? AB - OBJECTIVES: The impact of margin width on overall survival (OS) in the context of other prognostic factors after resection for colorectal liver metastases is unclear. We evaluated the relationship between resection margin and OS utilizing high-resolution histologic distance measurements. METHODS: A single-institution prospectively maintained database was queried for all patients who underwent an initial complete resection of colorectal liver metastases between 1992 and 2012. R1 resection was defined as tumor cells at the resection margin (0 mm). R0 resection was further divided into 3 groups: 0.1 to 0.9 mm, 1 to 9 mm, and 10 mm or greater. RESULTS: A total of 4915 liver resections were performed at Memorial Sloan Kettering Cancer Center between 1992 and 2012, from which 2368 patients were included in the current study. Half of the patients presented with synchronous disease, 43% had solitary metastasis, and the median tumor size was 3.4 cm. With a median follow-up for survivors of 55 months, the median OS of the R1, 0.1 to 0.9 mm, 1 to 9 mm, and 10 mm or more groups was 32, 40, 53, and 56 months, respectively (P < 0.001). Compared with R1 resection, all margin widths, including submillimeter margins correlated with prolonged OS (P < 0.05). The association between the margin width and OS remained significant when adjusted for all other clinicopathologic prognostic factors. CONCLUSIONS: Resection margin width is independently associated with OS. Wide margins should be attempted whenever possible. However, resection should not be precluded if narrow margins are anticipated, as submillimeter margin clearance is associated with improved survival. The prolonged OS observed with submillimeter margins is likely a microscopic surrogate for the biologic behavior of a tumor rather than the result of surgical technique. PMID- 26258317 TI - Treatment of 200 locally advanced (stage III) pancreatic adenocarcinoma patients with irreversible electroporation: safety and efficacy. AB - OBJECTIVES: Ablative therapies have been increasingly utilized in the treatment of locally advanced pancreatic cancer (LAPC). Irreversible electroporation (IRE) is an energy delivery system, effective in ablating tumors by inducing irreversible membrane destruction of cells. We aimed to demonstrate efficacy of treatment with IRE as part of multimodal treatment of LAPC. METHODS: From July 2010 to October 2014, patients with radiographic stage III LAPC were treated with IRE and monitored under a multicenter, prospective institutional review board approved registry. Perioperative 90-day outcomes, local failure, and overall survival were recorded. RESULTS: A total of 200 patients with LAPC underwent IRE alone (n = 150) or pancreatic resection plus IRE for margin enhancement (n = 50). All patients underwent induction chemotherapy, and 52% received chemoradiation therapy as well for a median of 6 months (range, 5-13 months) before IRE. IRE was successfully performed in all patients. Thirty-seven percent of patients sustained complications, with a median grade of 2 (range, 1-5). Median length of stay was 6 days (range, 4-36 days). With a median follow-up of 29 months, 6 patients (3%) have experienced local recurrence. Median overall survival was 24.9 months (range: 4.9-85 months). CONCLUSIONS: For patients with LAPC (stage III), the addition of IRE to conventional chemotherapy and radiation therapy results in substantially prolonged survival compared with historical controls. These results suggest that ablative control of the primary tumor may prolong survival. PMID- 26258318 TI - Prospective randomized double-blinded trial comparing 2 anti-MRSA agents with supplemental coverage of cefazolin before lower extremity revascularization. AB - OBJECTIVE: To compare with antibiotics with methicillin-resistant microbial coverage in a prospective fashion. BACKGROUND: Current antibiotic prophylaxis for vascular procedures includes a first generation cephalosporin. No changes in recommendations have occurred despite changes in reports of incidence of MRSA related surgical site infections. Does supplemental anti-MRSA prophylactic coverage provide a significant reduction in Gram-positive or MRSA infections? METHODS: Single center prospective double blinded randomized study of patients undergoing lower extremity vascular procedures from 2011 to 2014. One hundred seventy-eight (178) patients were evaluated at 90 days for surgical site infection. Infections were categorized as early infections less than 30 days of the index procedure and late after 90 days. RESULTS: Early vascular surgical site infection occurred in 7(8.24%) of patients in the Vancomycin arm, and 11 (11.83%) in the Daptomycin arm (P = 0.43). Gram-positive related infections and MRSA infections occurred in 1(1.18%)/0(0%) of Vancomycin patients and 9 (9.68%)/1 (1.08%) of Daptomycin patients, respectively (P < 0.02 and P = 1.00). Readmissions related to surgical site infections occurred in 4(4.71%) in the Vancomycin group and 11 (11.8%) in the Daptomycin group (P = 0.11). Patients undergoing operative exploration occurred in 5 (5.88%) in the Vancomycin group and 10 (10.75%) of the Daptomycin group (P = 0.17). Late infections were reported in 3 patients, 2 of which were in the combined Daptomycin group. Median hospital charges related to readmissions due to a surgical site infection was $50,823 in the combination Vancomycin arm and $110,920 in the combination Daptomycin group; however, no statistical significance was appreciated (P = 0.11). CONCLUSIONS: Vancomycin supplemental prophylaxis seems to reduce the incidence of Gram positive infection compared with adding supplemental Daptomycin prophylaxis. The Incidence of MRSA-related surgical site infections is low with the addition of either anti-MRSA agents compared with historical incidence of MRSA-related infection. PMID- 26258319 TI - Early versus late readmission after surgery among patients with employer-provided health insurance. AB - OBJECTIVES: To define the incidence of 90-day readmission and characterize the factors associated with 90-day readmission after 10 major surgical procedures. BACKGROUND: Most data on readmission focus solely on same hospital readmission (index hospitals) within 30 days of discharge. These studies may underestimate readmission, as patients may be readmitted beyond 30 days of discharge or to other non-index hospitals. METHODS: Patients discharged after 10 major surgical procedures (coronary artery bypass grafting, abdominal aortic aneurysm repair, carotid endarterectomy, aortic valve replacement, esophagectomy, pancreatectomy, pulmonary resection, hepatectomy, colectomy, and cystectomy) between 2010 and 2012 were identified from the Truven Health MarketScan Commercial Claims and Encounters database. Multivariable logistic regression analysis was performed to identify determinants of early (<=30 days) and late (31-90 days) readmission. RESULTS: A total of 158,753 patients were identified; 60.3% were male, and 42.3% had a Charlson Comorbidity Index of 2 or more. A total of 26,817 (16.9%) patients were readmitted within 90 days [early: 16,419 (10.4%) vs late: 10,398 (6.5%)]. Among readmitted patients, 38.3% were readmitted to a different hospital than the index hospital. Both early and late readmissions were more common at the index versus non-index hospital (early: 83.9% vs 16.1%; late: 75.0% vs 25.0%; both P < 0.001). In-hospital mortality after early readmission and late readmission was found to be lower at index hospitals than that at non-index hospitals (early; 0.7% vs 2.5%, P = 0.04; late; 0.2% vs 2.0%, P = 0.02). CONCLUSIONS: More than one third of readmission occurred after 30 days of index discharge. Approximately 20% of patients were readmitted to non-index hospitals. Assessment of 30 day same hospital readmissions underestimated the true incidence of readmission. PMID- 26258320 TI - FAST ultrasound examination as a predictor of outcomes after resuscitative thoracotomy: a prospective evaluation. AB - OBJECTIVE: The objective of this study was to examine the ability of Focused Assessment Using Sonography for Trauma (FAST) to discriminate between survivors and nonsurvivors undergoing resuscitative thoracotomy (RT). BACKGROUND: RT is a high-risk, low-salvage procedure performed in arresting trauma patients with poorly defined indications. METHODS: Patients undergoing RT from 10/2010 to 05/2014 were prospectively enrolled. A FAST examination including parasternal/subxiphoid cardiac views was performed before or concurrent with RT. The result was captured as adequate or inadequate with presence or absence of pericardial fluid and/or cardiac motion. A sensitivity analysis utilizing the primary outcome measure of survival to discharge or organ donation was performed. RESULTS: Overall, 187 patients arrived in traumatic arrest and underwent FAST. Median age 31 (1-84), 84.5% male, 51.3% penetrating. Loss of vital signs occurred at the scene in 48.1%, en-route in 23.5%, and in the ED in 28.3%. Emergent left thoracotomy was performed in 77.5% and clamshell thoracotomy in 22.5%. Sustained cardiac activity was regained in 48.1%. However, overall survival was only 3.2%. An additional 1.6% progressed to organ donation. FAST was inadequate in 3.7%, 28.9% demonstrated cardiac motion and 8.6% pericardial fluid. Cardiac motion on FAST was 100% sensitive and 73.7% specific for the identification of survivors and organ donors. CONCLUSIONS: With a high degree of sensitivity for the detection of potential survivors after traumatic arrest, FAST represents an effective method of separating those that do not warrant the risk and resource burden of RT from those who may survive. The likelihood of survival if pericardial fluid and cardiac motion were both absent was zero. PMID- 26258322 TI - The Society of Thoracic Surgeons voluntary public reporting initiative: the first 4 years. AB - OBJECTIVES: To evaluate participant characteristics and outcomes during the first 4 years of the Society of Thoracic Surgeons (STS) public reporting program. BACKGROUND: This is the first detailed analysis of a national, voluntary, cardiac surgery public reporting program using STS clinical registry data and National Quality Forum-endorsed performance measures. METHODS: The distributions of risk adjusted mortality rates, multidimensional composite performance scores, star ratings, and volumes for public reporting versus nonreporting sites were studied during 9 consecutive semiannual reporting periods (2010-2014). RESULTS: Among 8929 unique observations (~1000 STS participant centers, 9 reporting periods), 916 sites (10.3%) were classified low performing, 6801 (76.2%) were average, and 1212 (13.6%) were high performing. STS public reporting participation varied from 22.2% to 46.3% over the 9 reporting periods. Risk-adjusted, patient-level mortality rates for isolated coronary artery bypass grafting were consistently lower in public reporting versus nonreporting sites (P value range: <0.001 0.0077). Reporting centers had higher composite performance scores and star ratings (23.2% high performing and 4.5% low performing vs 7.6% high performing and 13.8% low performing for nonreporting sites). STS public reporting sites had higher mean annualized coronary artery bypass grafting volumes than nonreporting sites (169 vs 145, P < 0.0001); high-performing programs had higher mean coronary artery bypass grafting volumes (n = 241) than average (n = 139) or low-performing (n = 153) sites. Risk factor prevalence (except reoperation) and expected mortality rates were generally stable during the study period. CONCLUSIONS: STS programs that voluntarily participate in public reporting have significantly higher volumes and performance. No evidence of risk aversion was found. PMID- 26258321 TI - Tumor genotype determines phenotype and disease-related outcomes in thyroid cancer: a study of 1510 patients. AB - OBJECTIVES: To correlate thyroid cancer genotype with histology and outcomes. BACKGROUND: The prognostic significance of molecular signature in thyroid cancer (TC) is undefined but can potentially change surgical management. METHODS: We reviewed a consecutive series of 1510 patients who had initial thyroidectomy for TC with routine testing for BRAF, RAS, RET/PTC, and PAX8/PPARG alterations. Histologic metastatic or recurrent TC was tracked for 6 or more months after oncologic thyroidectomy. RESULTS: Papillary thyroid cancer (PTC) was diagnosed in 97% of patients and poorly differentiated/anaplastic TC in 1.1%. Genetic alterations were detected in 1039 (70%); the most common mutations were BRAFV600E (644/1039, 62%), and RAS isoforms (323/1039, 31%). BRAFV600E-positive PTC was often conventional or tall cell variant (58%), with frequent extrathyroidal extension (51%) and lymph node metastasis (46%). Conversely, RAS-positive PTC was commonly follicular variant (87%), with infrequent extrathyroidal extension (4.6%) and lymph node metastasis (5.6%). BRAFV600E and RET/PTC-positive PTCs were histologically similar. Analogously, RAS and PAX8/PPARG-positive PTCs were histologically similar. Compared with RAS or PAX8/PPARG-positive TCs, BRAFV600E or RET/PTC-positive TCs were more often associated with stage III/IV disease (40% vs 15%, P < 0.001) and recurrence (10% vs 0.7%, P < 0.001; mean follow-up 33 +/- 21 mo). Distant metastasis was highest in patients with RET/PTC-positive TC (10.8%, P = 0.02). CONCLUSIONS: In this large study of prospective mutation testing in unselected patients with TC, molecular signature was associated with distinctive phenotypes including cancers, with higher risks of both distant metastasis and early recurrence. Preoperative genotype provides valuable prognostic data to appropriately inform surgery. PMID- 26258323 TI - Complete pathologic response to pretransplant locoregional therapy for hepatocellular carcinoma defines cancer cure after liver transplantation: analysis of 501 consecutively treated patients. AB - OBJECTIVES: To evaluate the rate, effect, and predictive factors of a complete pathologic response (cPR) in patients with hepatocellular carcinoma (HCC) undergoing locoregional therapy (LRT) before liver transplantation (LT). BACKGROUND: Eligible patients with HCC receive equal model for end-stage liver disease prioritization, despite variable risks of tumor progression, waitlist dropout, and posttransplant recurrence. Pretransplant LRT mitigates these risks by inducing tumor necrosis. METHODS: Comparisons were made among HCC recipients with cPR (n = 126) and without cPR (n = 375) receiving pre-LT LRT (1994-2013). Multivariable predictors of cPR were identified. RESULTS: Of 501 patients, 272, 148, and 81 received 1, 2, and 3 or more LRT treatments. The overall, recurrence free, and disease-specific survival at 1-, 3-, and 5 years was 86%, 71%, 63%; 84%, 67%, 60%; and 97%, 90%, 87%. Compared with recipients without cPR, cPR patients had significantly lower laboratory model for end-stage liver disease scores, pretransplant alpha fetoprotein, and cumulative tumor diameters; were more likely to have 1 lesion, tumors within Milan/University of California, San Francisco (UCSF) criteria, LRT that included ablation, and a favorable tumor response to LRT; and had superior 1-, 3-, and 5-year recurrence-free survival (92%, 79%, and 73% vs 81%, 63%, and 56%; P = 0.006) and disease-specific survival (100%, 100%, and 99% vs 96%, 89%, and 86%; P < 0.001) with only 1 cancer-specific death and fewer recurrences (2.4% vs 15.2%; P < 0.001). Multivariate predictors of cPR included a favorable post-LRT radiologic/alpha fetoprotein tumor response, longer time interval from LRT to LT, and lower model for end-stage liver disease score and maximum tumor diameter (C-statistic 0.75). CONCLUSIONS: Achieving cPR in patients with HCC receiving LRT strongly predicts tumor-free survival. Factors predicting cPR are identified, allowing for differential prioritization of HCC recipients based on their variable risks of post-LT recurrence. Improving LRT strategies to maximize cPR would enhance posttransplant cancer outcomes. PMID- 26258324 TI - Collected world experience about the performance of the snorkel/chimney endovascular technique in the treatment of complex aortic pathologies: the PERICLES registry. AB - OBJECTIVES: We sought to analyze the collected worldwide experience with use of snorkel/chimney endovascular aneurysm repair (EVAR) for complex abdominal aneurysm treatment. BACKGROUND: EVAR has largely replaced open surgery worldwide for anatomically suitable aortic aneurysms. Lack of availability of fenestrated and branched devices has encouraged an alternative strategy utilizing parallel or snorkel/chimney grafts (ch-EVAR). METHODS: Clinical and radiographic information was retrospectively reviewed and analyzed on 517 patients treated by ch-EVAR from 2008 from 2014 by prearranged defined and documented protocols. RESULTS: A total of 119 patients in US centers and 398 in European centers were treated during the study period. US centers preferentially used Zenith stent-grafts (54.2%) and European centers Endurant stent-grafts (62.2%) for the main body component. Overall 898 chimney grafts (49.2% balloon expandable, 39.6% self-expanding covered stents, and 11.2% balloon expandable bare metal stents) were placed in 692 renal arteries, 156 superior mesenteric arteries (SMA), and 50 celiac arteries. At a mean follow-up of 17.1 months (range: 1-70 months), primary patency was 94%, with secondary patency of 95.3%. Overall survival of patients in this high-risk cohort for open repair at latest follow-up was 79%. CONCLUSIONS: This global experience represents the largest series in the ch-EVAR literature and demonstrates comparable outcomes to those in published reports of branched/fenestrated devices, suggesting the appropriateness of broader applicability and the need for continued careful surveillance. These results support ch-EVAR as a valid off-the-shelf and immediately available alternative in the treatment of complex abdominal EVAR and provide impetus for the standardization of these techniques in the future. PMID- 26258325 TI - The Adult Phenotype of Tuberous Sclerosis Complex. PMID- 26258326 TI - Hydrogen alpha laser ablation plasma diagnostics. AB - Spectral measurements of the H(alpha) Balmer series line and the continuum radiation are applied to draw inferences of electron density, temperature, and the level of self-absorption in laser ablation of a solid ice target in ambient air. Electron densities of 17 to 3.2*10(24) m(-3) are determined from absolute calibrated emission coefficients for time delays of 100-650 ns after generation of laser plasma using Q-switched Nd:YAG radiation. The corresponding temperatures of 4.5-0.95 eV were evaluated from the absolute spectral radiance of the continuum at the longer wavelengths. The redshifted, Stark-broadened hydrogen alpha line emerges from the continuum radiation after a time delay of 300 ns. The electron densities inferred from power law formulas agree with the values obtained from the plasma emission coefficients. PMID- 26258327 TI - High Purcell factor in fiber Bragg gratings utilizing the fundamental slow-light mode. AB - We demonstrate through numerical simulations that the slow-light resonances that exist in strong, apodized fiber Bragg gratings (FBGs) fabricated with femtosecond pulses in deuterium-loaded fibers can exhibit very large intensity enhancements and Purcell factors with the proper optimization of their length. This potential is illustrated with two saturated FBGs that are less than 5 mm long and have been annealed to reduce their internal loss. The first one exhibits the largest measured Purcell factor in an all-fiber device (38.7), and the second one exhibits the largest intensity enhancement (1525). These devices are anticipated to have significant applications in quantum-dot lasers, nonlinear fiber devices, and cavity quantum-electrodynamics experiments. PMID- 26258328 TI - Characterization of C-apertures in a successful demonstration of heat-assisted magnetic recording. AB - An optical pump-probe setup was used to measure the coercivity change in a heat assisted magnetic recording (HAMR) medium. The incident optical power required to attain the Curie temperature of the medium was determined by calculating its coercivity from BH loops under different illuminating laser powers through use of the Kerr signal in the pump-probe setup. The HAMR medium was then illuminated through an array of square and C-shaped nanoapertures so that the necessary laser power required for magnetic reversal could be compared to the bulk case. Magnetic force microscopy and Kerr microscopy revealed that C-apertures were able to permit heating of the magnetic medium and lower the coercivity to achieve magnetic reversal whereas the square apertures were not. The results show that aperture shape and design play a large role in HAMR head designs. PMID- 26258329 TI - Photonic crystal fiber polarization rotator based on the topological Zeeman effect. AB - A photonic crystal fiber polarization rotator (PR) is proposed based on the topological Zeeman effect. The proposed PR is achieved by permanently twisting a segment of sixfold symmetric photonic crystal fiber with a matched length, and under the optimized parameters, the PR can offer an almost 100% polarization conversion ratio in the wavelength of 1.55-MUm band (~200 nm bandwidth) and a compact length of about 157 MUm based on the numerical simulation result of the full-vector finite-element method. The proposed in-line PCF PR can be easily fabricated based on state-of-art PCF manufacturing, and it is a potential inexpensive candidate in the application of modern communication systems. PMID- 26258330 TI - Sinusoidal ghost imaging. AB - We introduce sinusoidal ghost imaging (SGI), which uses 2D orthogonal sinusoidal patterns instead of random patterns in "computational ghost imaging" (CGI). Simulations and experiments are performed. In comparison with the"differential ghost imaging" algorithm that was used to improve the SNR of ghost imaging, results of SGI show about 3 orders of magnitude higher SNR, which can be reconstructed even with a much smaller number of patterns. More importantly, based on the results, SGI provides the great opportunity to generate innate processed images by predefined selection of patterns. This can speed up detection process considerably and paves the way for real applications. PMID- 26258331 TI - Branch-cut algorithm for optical phase unwrapping. AB - In this Letter, a proposal addressing the problem of two-dimensional phase unwrapping based on the theory of residues is presented. Here, wrapped phase maps with shifted phase jumps are used to balance residue charges. With this approach, we seek to minimize processing time and residue connection, which is essential in the development of branch-cut algorithms. Finally, a phase-unwrapping algorithm is applied to these wrapped maps, generated by Fourier transform profilometry to obtain three-dimensional profiles of objects illuminated by photorefractive moire like patterns generated in an experiment of real-time dynamic holography, and by fringe patterns generated with a Michelson interferometer. PMID- 26258332 TI - Two-frame tilt-shift error estimation and phase demodulation algorithm. AB - We present an algorithm capable of performing fringe pattern phase demodulation from two frames with unknown, linearly nonuniform phase shift, i.e., under presence of the tilt-shift error. The method consists of intensity-based filtration of the tilt-shift component and subsequent two steps of a nonlinear error functional minimization. We verify the algorithm performance and robustness using both simulated and experimental data, indicating high accuracy of the presented method and its good numerical properties. Both small and large tilts can be treated. The Letter is complemented by numerical codes available online in Wielgus, "Two-frame tilt-shift error estimation and phase demodulation algorithm" (2015). PMID- 26258333 TI - In situ characterization of few-cycle laser pulses in transient absorption spectroscopy. AB - Attosecond transient absorption spectroscopy has thus far been lacking the capability to simultaneously characterize the intense laser pulses at work within a time-resolved quantum-dynamics experiment. However, precise knowledge of these pulses is key to extracting quantitative information in strong-field highly nonlinear light-matter interactions. Here, we introduce and experimentally demonstrate an ultrafast metrology tool based on the time-delay-dependent phase shift imprinted on a strong-field-driven resonance. Since we analyze the signature of the laser pulse interacting with the absorbing spectroscopy target, the laser pulse duration and intensity are determined in situ. As we also show, this approach allows for the quantification of time-dependent bound-state dynamics in one and the same experiment. In the future, such experimental data will facilitate more precise tests of strong-field dynamics theories. PMID- 26258334 TI - Generation of Kerr combs centered at 4.5 MUm in crystalline microresonators pumped with quantum-cascade lasers. AB - We report on the generation of mid-infrared Kerr frequency combs in high-finesse CaF2 and MgF2 whispering-gallery-mode resonators pumped with continuous-wave room temperature quantum cascade lasers. The combs were centered at 4.5 MUm, the longest wavelength to date. A frequency comb wider than one half of an octave was demonstrated when approximately 20 mW of pump power was coupled to an MgF2 resonator characterized with quality factor exceeding 10(8). PMID- 26258335 TI - Fresnel transform as a projection onto a Nijboer-Zernike basis set. AB - The Fresnel transform is widely used in optics to calculate the free-space propagation of paraxial fields. Generally, there is no analytical solution for the Fresnel transform; therefore, the numerical methods are used often. In this Letter, we propose a new semi-analytical method to calculate the Fresnel transform, which is based on an extended Nijboer-Zernike theory. We calculate two examples to investigate how the sampling rate and maximal number of Zernike polynomials affect the accuracy of our results, and then use this method to calculate the reconstruction of two different kinds of holograms. At the end, we discuss the advantages and disadvantages of our method. PMID- 26258336 TI - Remote mid-infrared photoacoustic spectroscopy with a quantum cascade laser. AB - We demonstrate non-contact remote photoacoustic spectroscopy in the mid-infrared region. A room-temperature-operated pulsed external-cavity quantum cascade laser is used to excite photoacoustic waves within a semitransparent sample. The ultrasonic waves are detected remotely on the opposite side of the sample using a fiber-optic Mach-Zehnder interferometer, thereby avoiding problems associated with acoustic attenuation in air. We present the theoretical background of the proposed technique and demonstrate measurements on a thin polystyrene film. The obtained absorption spectrum in the region of 1030-1230 cm(-1) is compared to a spectrum obtained by attenuated total reflection, showing reasonable agreement. PMID- 26258337 TI - Characterization of nonlinear properties of black phosphorus nanoplatelets with femtosecond pulsed Z-scan measurements. AB - The nonlinear properties of black phosphorus (BP) nanoplatelets (NPs) have been characterized with Z-scan measurements under 800-nm femtosecond pulsed laser excitation. A transition from saturable absorption (SA) to reverse saturable absorption (RSA) with the increase of laser intensity was observed in the open aperture (OA) measurements. Simultaneously, closed-aperture (CA) measurements were carried out to investigate the nonlinear refractive index of BP NPs together, and a value of n(2) ?(6.8+/-0.2)*10(-13) m2/W was obtained. The nonlinear absorption properties were analyzed according to the band structure of BP. A theoretical analysis based on SA and two-photon absorption (TPA) was used to determine the nonlinear absorption coefficients from the experimental results, and the TPA coefficient at 800 nm was estimated about (4.5+/-0.2)*10(-10) m/W. PMID- 26258338 TI - Label-free imaging of thick tissue at 1550 nm using a femtosecond optical parametric generator. AB - We have developed a simple wavelength-tunable optical parametric generator (OPG), emitting broadband ultrashort pulses with peak wavelengths at 1530-1790 nm, for nonlinear label-free microscopy. The OPG consists of a periodically poled lithium niobate crystal, pumped at 1064 nm by a ultrafast Yb:fiber laser with high pulse energy. We demonstrate that this OPG can be used for label-free imaging, by third harmonic generation, of nuclei of brain cells and blood vessels in a >150 MUm thick brain tissue section, with very little decay of intensity with imaging depth and no visible damage to the tissue at an incident average power of 15 mW. PMID- 26258339 TI - Adaptive mode control based on a fiber Bragg grating. AB - We experimentally demonstrated adaptive control of linearly polarized (LP) modes in a two-mode fiber. Our method is based on a stepwise adaptive optics algorithm, with feedback determined by the relative magnitude of optical power reflected by a fiber Bragg grating and the transmitted power. Selective excitations of the LP01 and LP11 modes are experimentally shown. PMID- 26258340 TI - Spatiotemporal pulse shaping using resonant diffraction gratings. AB - We propose a new theoretical model describing spatiotemporal transformations of two-dimensional optical pulses by resonant diffraction gratings. The diffraction of the pulse is described in terms of a linear system. Simple analytical approximations for the transfer function and the impulse response of the system are derived. The derived approximations contain five independent parameters, which can be estimated using the rigorous coupled-wave analysis. The presented numerical simulation results demonstrate that the resonant grating can perform complex pulse transformations, such as the simultaneous spatial and temporal differentiation of the optical pulse envelope. PMID- 26258341 TI - Diffraction by three-dimensional slit-shape curves: decomposition in terms of Airy and Pearcey functions. AB - We analyze the diffraction field generated by coherent illumination of a three dimensional transmittance characterized by a slit-shape curve. Generic features are obtained using the Frenet-Serret equations, which allow a decomposition of the optical field. The analysis is performed by describing the influence of the curvature and torsion on osculating, normal, and rectifying planes. We show that the diffracted field has a decomposition in three optical fields propagating along three optical axes that are mutually perpendicular. The decomposition is in terms of the Pearcey and Airy functions, and the generalized Airy function. Experimental results are shown. PMID- 26258342 TI - Simple all-PM-fiber laser mode-locked with a nonlinear loop mirror. AB - In this Letter, we present a figure-eight all-PM-fiber laser oscillator design with a nonlinear optical loop mirror as an artificial saturable absorber. Unlike previous constructions using the same mode-locking technique, our cavity is constructed entirely of polarization-maintaining (PM) fibers, making the oscillator more resistant to thermal and mechanical perturbations. Two simple and robust laser configurations that differ by the output coupling ratio (70% or 30%) are presented. The first configuration delivers high energy pulses of 3.5 nJ, and the second configuration delivers pulses of 1.6 nJ at a common repetition rate of 15 MHz. In either configuration, the pulsed operation is stable, and the laser operates in a single pulse train regime, even for pump powers approaching twice the power required for mode-locking. We have also observed that, at higher intracavity powers, stimulated Raman scattering plays a significant role. PMID- 26258343 TI - Design of mechanically-tunable photonic crystal split-beam nanocavity. AB - Photonic crystal split-beam nanocavities allow for ultra-sensitive optomechanical transductions but are degraded due to their relatively low optical quality factors. We have proposed and experimentally demonstrated a new type of one dimensional photonic crystal split-beam nanocavity optimized for an ultra-high optical-quality factor. The design is based on the combination of the deterministic method and hill-climbing algorithm. The latter is the simplest and most straightforward method of the local search algorithm that provides the local maximum of the chosen quality factors. This split-beam nanocavity is made up of two mechanical uncoupled cantilever beams with Bragg mirrors patterned onto it and separated by a 75-nm air gap. Experimental results emphasize that the quality factor of the second-order TE mode can be as high as 1.99*10(4). Additionally, one beam of the device is actuated in the lateral direction with the aid of a NEMS actuator, and the quality factor maintains quite well even if there is a lateral offset up to 64 nm. Potentially promising applications, such as sensitive optomechanical torque sensor, local tuning of Fano resonance, all-optical reconfigurable filters, etc., are foreseen. PMID- 26258344 TI - Photonic microwave phase shifter based on dual-sideband phase-control technique. AB - An all-optical photonic microwave phase shifter that can realize a continuous 0 degrees -360 degrees phase shift is presented. The phase-shifting operation is implemented by controlling the phase of the two RF phase-modulation sidebands while keeping the optical carrier phase fixed. The use of two RF modulation sidebands, instead of a single sideband used in most conventional phase shifters, has the advantage of high-output RF signal power, and consequently high signal-to noise ratio performance. Experimental results demonstrate the full -180 degrees to +180 degrees phase shift over a wide microwave frequency range from 11 to 26.5 GHz, and 14 dB increase in the output RF signal power compared to a conventional phase shifter. PMID- 26258345 TI - Broad working bandwidth and "endlessly" single-mode guidance within hybrid silicon photonics. AB - The successes of nonlinear photonics and hybrid silicon photonics with a growing variety of functional materials entail ever-enlarging bandwidths. It is best exemplified by parametric comb frequency generation. Such operation challenges the dielectric channel waveguide as the basis for guidance, because of the adverse advent of higher order modes at short wavelengths. Surprisingly, the popular mechanism of endlessly single-mode guidance [Opt. Lett.22, 961 (1997).] operating in photonic crystal fibers has not been transposed within silicon photonics yet. We outline here the strategy and potential of this approach within planar and hybrid silicon photonics, whereby in-plane and vertical confinement are shown to be amenable to near-single-mode behavior in the typical silicon band, i.e., lambda=1.1 MUm to ~5 MUm. PMID- 26258346 TI - Miniature and robust optical fiber in-line Mach-Zehnder interferometer based on a hollow ellipsoid. AB - An optical fiber in-line Mach-Zehnder interferometer based on a hollow ellipsoid fabricated by femtosecond laser micromachining and fusion-splicing technique is demonstrated. The surface of the hollow ellipsoid acts as an internal mirror that can be utilized for the construction of an interferometer. Such an interferometer device is miniature and robust and can perform external refractive index, curvature, and high-temperature sensing in a mutually independent way, and hence a simultaneous multiple parameter measurement capability can be readily achieved. PMID- 26258347 TI - Compact polarization-maintaining 2.05-MUm fiber laser at 1-MHz and 1-MW peak power. AB - We report on a compact all-polarization-maintaining 2.05-MUm chirped pulse fiber amplifier system emitting pulses at up to 1-MW peak power level at 371-fs pulse duration. The seed pulse repetition rate provided by an inhouse-built oscillator is reduced to around 1 MHz using a pulse picker. In combination with a two stage fiber amplifier, output pulse energies up to 570 nJ are obtained without the need of a high-power large-mode area amplifier. Both temporal stretching and compression of the chirped pulse amplifier design are achieved using a single chirped volume Bragg grating. PMID- 26258348 TI - Diode-side-pumped continuous wave Nd3+ : YVO4 self-Raman laser at 1176 nm. AB - Here we report, to the best of our knowledge, the first diode-side-pumped continuous wave (cw) Nd3+:YVO4 self-Raman laser operating at 1176 nm. The compact cavity design is based on the total internal reflection of the laser beam at the pumped side of the Nd3+:YVO4 crystal. Configurations with a single bounce and a double bounce of the laser beam at the pumped faced have been characterized, providing a quasi-cw peak output power of more than 8 W (multimode) with an optical conversion efficiency of 11.5% and 3.7 W (TEM00) having an optical conversion efficiency of 5.4%, respectively. Cw output power of 1.8 W has been demonstrated. PMID- 26258349 TI - Variation around a pyramid theme: optical recombination and optimal use of photons. AB - We propose a new type of wave-front sensor (WFS) derived from the pyramid WFS (PWFS). This new WFS, called the flattened pyramid-WFS (FPWFS), has a reduced pyramid angle in order to optically overlap the four pupil images into an unique intensity. This map is then used to derive the phase information. In this Letter, this new WFS is compared to three existing WFSs, namely the PWFS, the modulated PWFS (MPWFS), and the Zernike WFS (ZWFS) following tests about sensitivity, linearity range, and low-photon-flux behavior. The FPWFS turns out to be more linear than a modulated pyramid for the high-spatial order aberrations, but it provides an improved sensitivity compared to the non-modulated pyramid. The noise propagation may even be as low as the ZWFS for some given radial orders. Furthermore, the pixel arrangement being more efficient than for the PWFS, the FPWFS seems particularly well suited for high-contrast applications. PMID- 26258350 TI - Iterative phase-retrieval method for generating stereo array of polarization controlled focal spots. AB - This Letter introduces an iterative phase-retrieval method based on the Gerchberg Saxton (G-S) algorithm for generating any arbitrary 3D pattern in image space, while simultaneously controlling the polarization orientation at each pixel. For proof-of-principle, we generate a stereo focal spot array with distinct polarization orientation for each spot. This method is universal for controlling the output polarization; the only requirement is that the input polarization should be spatially inhomogeneous. This work has the potential to impact coherent imaging techniques and spectroscopy. PMID- 26258351 TI - Noisy metamolecule: strong narrowing of fluorescence line. AB - We consider a metamolecule consisting of a bosonic mode correlated with a two level system (TLS): it can be, for example, a plasmonic mode interacting with a quantum dot. We focus on the parameter range where all the correlations are strong and of the same order. The interaction between the bosonic mode is correlated with the TLS, external coherent drive, and dissipation. Quantum Monte Carlo simulations show that the fluorescence of this system at dissipation is larger than the driving amplitude and shows a strong (by the order of magnitude) narrowing of its spectral line. This effect may be related to kind of a quantum stochastic resonance. We show that the fluorescence corresponds to the finite domain over the coherent drive with sharp, low threshold, and that the Wigner function splits. PMID- 26258352 TI - Blue-light Fourier-domain optical-coherence microscopy with linear k-sampling using second-harmonic generation. AB - We demonstrate Fourier-domain optical-coherence microscopy (OCM) method that uses blue light for high-resolution microscopic imaging. Spectrally broad bandwidth is obtained by means of second-harmonic generation of Ti:sapphire laser light on the nonlinear crystal. Angular scanning of the crystal performed by a resonant scanner results in second-harmonic generation for a broad range of frequencies producing blue light with central wavelength of 402 nm and bandwidth of 35 nm in one cycle. The axial resolution of the new setup is 3.5 MUm in air, and the transverse resolution for Olympus 40* objective lens is 2.7 MUm in X direction and 3.2 MUm in Y direction. The developed technique enables registering spectral interferometric signal directly in k domain. Additionally, we present examples of imaging a biological specimen using the newly developed method. PMID- 26258353 TI - Absolute terahertz power measurement of a time-domain spectroscopy system. AB - We report on, to the best of our knowledge, the first absolute terahertz (THz) power measurement of a photoconductive emitter developed for time-domain spectroscopy (TDS). The broadband THz radiation emitted by a photoconductor optimized for the excitation with 1550-nm femtosecond pulses was measured by an ultrathin pyroelectric thin-film (UPTF) detector. We show that this detector has a spectrally flat transmission between 100 GHz and 5 THz due to special conductive electrodes on both sides of the UPTF. Its flat responsivity allows the calibration with a standard detector that is traceable to the International System of Units (SI) at the THz detector calibration facility of PTB. Absolute THz power in the range from below 1 MUW to above 0.1 mW was measured. PMID- 26258354 TI - Dual-transverse-mode microsquare lasers with tunable wavelength interval. AB - A dual-transverse-mode microsquare laser with a tunable wavelength interval is designed and realized by using a square-ring-patterned contact window. For a 30 MUm-side-length microsquare laser with the square-ring width of 4 MUm, the wavelength interval varies from 0.25 to 0.37 nm with the intensity ratio less than 2.5 dB as the injection current increases from 89 to 108 mA. Based on the dual-transverse-mode microsquare laser, the microwave signals with the frequencies of 30.56, 32.70, 35.12, and 39.51 GHz and the 3-dB bandwidths of 47, 53, 54, and 47 MHz are obtained at the injection currents of 90, 95, 100, and 105 mA, respectively. PMID- 26258355 TI - Efficient Yb3+:CaGdAlO4 bulk and femtosecond-laser-written waveguide lasers. AB - We report on, to the best of our knowledge, the first fs-laser-written waveguide laser in Yb3+:CaGdAlO4 (Yb:CALGO). With Yb:CALGO crystals grown in our labs, we obtained a slope efficiency of 69% and up to 2.4 W of continuous wave (cw) output power in a waveguide-laser configuration. Moreover, bulk laser experiments with Yb:CALGO were performed, and slope efficiencies up to 73%, optical-to-optical efficiencies of 65%, and maximum cw output powers of 3.3 W were reached. These are the highest efficiencies in the laser configuration with Yb:CALGO. PMID- 26258356 TI - Low-power microelectromechanically tunable silicon photonic ring resonator add drop filter. AB - We experimentally demonstrate a microelectromechanically (MEMS) tunable photonic ring resonator add-drop filter, fabricated in a simple silicon-on-insulator (SOI) based process. The device uses electrostatic parallel plate actuation to perturb the evanescent field of a silicon waveguide, and achieves a 530 pm resonance wavelength tuning, i.e., more than a fourfold improvement compared to previous MEMS tunable ring resonator add-drop filters. Moreover, our device has a static power consumption below 100 nW, and a tuning rate of -62 pm/V, i.e., the highest reported rate for electrostatic tuning of ring resonator add-drop filters. PMID- 26258357 TI - Dual-wavelength eye-safe Nd:YAP Raman laser. AB - We report on a diode-pumped, Q-switched intracavity-Raman-shifted Nd-doped yttrium-aluminum-perovskite (Nd:YAP) laser using potassium titanyl phosphate (KTP) or potassium titanyl arsenate (KTA) nonlinear crystals to produce eye-safe radiation. In both cases, we obtained simultaneous laser emission at two wavelengths corresponding to distinct Raman gain peaks and different Stokes orders for the nonlinear crystal used. From the Nd:YAP/KTP laser source, we obtained 3 ns pulses of combined 21 kW peak power at 1478 and 1503 nm. From the Nd:YAP/KTA laser source, we obtained up to 220 mW total average output power, equally split between 1474 and 1480 nm emission lines. PMID- 26258358 TI - Extended depth-of-field 3D endoscopy with synthetic aperture integral imaging using an electrically tunable focal-length liquid-crystal lens. AB - Conventional synthetic-aperture integral imaging uses a lens array to sense the three-dimensional (3D) object or scene that can then be reconstructed digitally or optically. However, integral imaging generally suffers from a fixed and limited range of depth of field (DOF). In this Letter, we experimentally demonstrate a 3D integral-imaging endoscopy with tunable DOF by using a single large-aperture focal-length-tunable liquid crystal (LC) lens. The proposed system can provide high spatial resolution and an extended DOF in synthetic-aperture integral imaging 3D endoscope. In our experiments, the image plane in the integral imaging pickup process can be tuned from 18 to 38 mm continuously using a large-aperture LC lens, and the total DOF is extended from 12 to 51 mm. To the best of our knowledge, this is the first report on synthetic aperture integral imaging 3D endoscopy with a large-aperture LC lens that can provide high spatial resolution 3D imaging with an extend DOF. PMID- 26258359 TI - Fast photoacoustic-guided depth-resolved Raman spectroscopy: a feasibility study. AB - In this Letter, photoacoustic-guided Raman spectroscopy (PARS) is proposed for a fast depth-resolved Raman measurement with accurate depth localization. The approach was experimentally demonstrated to receive both photoacoustic and Raman signals from a three-layer agar phantom based on a developed synergic photoacoustic-Raman probe, showing strong depth correlation and achieving magnitude of faster operation speed due to photoacoustic time-of-flight measurement and guidance, compared with the conventional depth-resolved Raman spectroscopy method. In addition, further combination with advanced optical focusing techniques in biological-scattering medium could potentially enable the proposed approach for cancer diagnostics with both tight and fast optical focusing at the desired depth of tumor. PMID- 26258360 TI - Solid-state laser wavelength selection and tuning by fused-silica-transmission gratings with subwavelength deep-surface relief. AB - Wavelength selection and tuning of pulsed Ti:sapphire and Nd:YAG lasers is realized, to the best of our knowledge, for the first time by subwavelength surface-relief fused-silica-transmission gratings (SG). High efficiency, high laser damage threshold, and other advantages of these gratings are confirmed by several intracavity laser experiments. PMID- 26258361 TI - Microfiber-coupler-assisted control of wavelength tuning for Q-switched fiber laser with few-layer molybdenum disulfide nanoplates. AB - Based on the liquid exfoliated method, we obtained the few-layer molybdenum disulfide (MoS2) nanoplates solution. By thermal evaporation method, we directly deposited MoS2 thin film onto the facet of a fiber patch cord. The modulation depth of the film is as high as 29%, and a Q-switched fiber laser was achieved. We also provided a new method to continuously tune the output laser with a tuning sensitivity of ~5.5 nm/(1% strain) by controlling the cavity loss with a strained microfiber coupler (MFC). PMID- 26258362 TI - Up/down conversion switching by adjusting the pulse width of red laser beams in LaF3:Tm3+ nanocrystals. AB - We demonstrate a versatile approach to fine-tuning the ratio of blue to near infrared emission intensity from Tm3+ ions in LaF3 nanocrystals by adjusting the pulse widths and excitation wavelengths of red laser beams. The mechanism of color-tunable Tm3+ emission by pulse widths is explored, and a mechanism based on promoting the population of some luminescence levels and cutting off the population of others by suitably adjusting pulse duration is proposed. The underlying reason of excitation wavelength-modulated emission is ascribed to tuning absorption probability ratio of ground state absorption to excited state absorption by tuning the matching degree between the energies of excitation wavelength and ground (excited) state absorption of Tm3+. The ability of our LaF3:Tm3+ nanocrystals to emit variable emissions on demand in response to pulse width and excitation wavelength provides keen insights into controlling the population processes of luminescent levels and offers a versatile approach for tuning the spectral output. PMID- 26258363 TI - Dispersive-wave-based octave-spanning supercontinuum generation in InGaP membrane waveguides on a silicon substrate. AB - We demonstrate the generation of an octave-spanning supercontinuum in InGaP membrane waveguides on a silicon substrate pumped by a 1550-nm femtosecond source. The broadband nature of the supercontinuum in these dispersion-engineered high-index-contrast waveguides is enabled by dispersive wave generation on both sides of the pump as well as by the low nonlinear losses inherent to the material. We also measure the coherence properties of the output spectra close to the pump wavelength and find that the supercontinuum is highly coherent at least in this wavelength range. PMID- 26258364 TI - Landau damping of electromagnetic transport via dielectric-metal superlattices. AB - We discuss the propagation of electromagnetic waves through a one-dimensional periodic array of bilayers with metal inclusions. We show that the nonlocality of metal conductivity leads to the emergence of the fundamental collisionless Landau damping. It cannot be neglected, not only when prevailing over ordinary collision damping, but even when these two kinds of electromagnetic absorption are of the same order. Landau damping always exists and considerably alters the photonic transmission of the array within the THz and near-infrared frequency range. PMID- 26258365 TI - Top-hat random fiber Bragg grating. AB - We examined the possibility of using noise or pseudo-random variations of the refractive index in the design of fiber Bragg gratings (FBGs). We demonstrated theoretically and experimentally that top-hat FBGs may be designed and fabricated using this approach. The reflectivity of the fabricated top-hat FBG matches quite well with that of the designed one. PMID- 26258366 TI - Overcoming the limitation of phase retrieval using Gerchberg-Saxton-like algorithm in optical fiber time-stretch systems. AB - We investigate the fundamental limitation of the full-field retrieval of optical pulses based on a time-equivalent Gerchberg-Saxton (GS)-like algorithm, in which the Fourier transformation of the temporal signal is performed by the group velocity dispersion (GVD) of optical fibers. The insufficient knowledge of the input pulse intensity fundamentally limited by the bandwidth of the photodetector influences the accuracy of the retrieved phase using the algorithm. To this end, we propose a modified GS algorithm, which involves multi-step intensity-only measurements, to mitigate this limitation. By studying the influence of spectral phase and amplitude modulations on the retrieval error, we show that the modified GS algorithm demonstrates a significant improvement in phase retrieval accuracy. More importantly, we anticipate the present study will provide valuable insight in understanding how the spectral variation generally influences the recovery accuracy in time-stretch-based GS algorithm, and thus identify its potential applications, particularly for those requiring ultrafast measurements. PMID- 26258367 TI - Giant enhancement of upconversion emission in (NaYF4:Nd3+/Yb3+/Ho3+)/(NaYF4:Nd3+/Yb3+) core/shell nanoparticles excited at 808 nm. AB - In this work, colloidal hexagonal-phase (NaYF4:Nd3+/Yb3+/Ho3+)/(NaYF4:Nd3+/Yb3+) core/shell nanoparticles with intense visible upconversion emissions under 808-nm laser excitation were prepared. Compared with the core-only nanoparticles, a maximum 990-fold overall enhancement in the emission intensity of Ho3+ ions was achieved with the help of active-shell coating design, due to the significant increase in the near-infrared absorption and efficient energy transfer from Nd3+ primary-sensitizers to Ho3+ activators via Yb3+ bridging sensitizers. The luminescence-enhancement effect exhibited a strong dependence on the doping concentrations of NaYF4:Nd3+/Yb3+ active-shell. The optimal concentrations of Nd3+ and Yb3+ ions in the active-shell layer were found to be 30 and 5 mol. %, respectively. Moreover, the upconversion emission intensity of NaYF4:Nd3+/Yb3+ coated nanoparticles was about 2.5 times higher than the one coated with a NaYF4:Nd3+ active-shell. PMID- 26258368 TI - Anderson localization in a partially random Bragg grating and a conserved area theorem. AB - We investigate the gradual emergence of the disorder-related phenomena in intermediate regimes between a deterministic periodic Bragg grating and a fully random grating and highlight two critical properties of partially disordered Bragg gratings. First, the integral of the logarithm of the transmittance over the reciprocal wavevector space is a conserved quantity. Therefore, adding disorder merely redistributes the transmittance over the reciprocal space. Second, for any amount of disorder, the average transmittance decays exponentially with the number of grating layers in the simple form of exp(-etaN) for sufficiently large N, where eta is a constant, and N is the number of layers. Conversely, the simple exponential decay form does not hold for small N except for a highly disordered system. Implications of these findings are demonstrated. PMID- 26258369 TI - Optical spectroscopy of Cr3+-doped transparent nano-glass ceramics for lifetime based temperature sensing. AB - Transparent bulk glass ceramic containing Cr3+:LiGa5O8 nanoparticles was fabricated as an alternative for monocrystal to explore the possible application in fluorescence lifetime-based temperature sensing. Such glass ceramic exhibited deep-red luminescence upon the excitation of the wide wavelength range of visible light. Impressively, the Cr3+ lifetime dramatically decreased from 2.45 to 0.22 ms with the temperature increasing from 293 to 563 K, owing to the competition of radiation transitions from the thermally coupled 2E and 4T2 excited states. A two level kinetic model was adopted to interpret this temperature-dependent luminescence of Cr3+, which gave a highest temperature sensitivity of 1.15% K( 1). PMID- 26258370 TI - Physical unsharp mask with structured detection. AB - We present a method to implement physically an unsharp mask filter in an imaging system. The idea is based on the use of a spatially periodic variation in the detection efficiency of an area detector. Such a "structured detection" introduces harmonic peaks in the Fourier spectrum associated with the image, enabling the use of higher spatial frequencies that would otherwise be inaccessible, due to the system point spread function. The result is an effective deblurring of the image implemented in hardware, i.e., before the detection noise occurs. The method is first demonstrated via a numerical simulation and then validated using experimental neutron imaging data. PMID- 26258371 TI - Generation of phase difference between self-mixing signals in a-cut Nd:YVO4 laser with a waveplate in the external cavity. AB - We present a novel method using Nd:YVO4 laser with a waveplate in the external cavity to generate two orthogonally polarized signals with stable and adjustable phase difference. The phase difference is observed in the presence of external interference, and it is determined by the phase retardation of the waveplate. A model based on birefringent external-interference effect is proposed to theoretically explain the phase difference phenomenon, and the arithmetic solution of the relation between the phase difference and the phase retardation of waveplate is given. The simulated results accord with the experimental phenomena. This Letter provides the possibility for the measurement of phase retardation and also offers guidance to the design of interferometers based on fringe counting technique. PMID- 26258373 TI - Formation of in-volume nanogratings with sub-100-nm periods in glass by femtosecond laser irradiation. AB - We present direct experimental observation of the morphological evolution during the formation of nanogratings with sub-100-nm periods with the increasing number of pulses. Theoretical simulation shows that the constructive interference of the scattering light from original nanoplanes will create an intensity maximum located between the two adjacent nanoplanes, resulting in shortening the nanograting period by half. The proposed mechanism explains the formation of nanogratings with periods beyond those predicted by the nanoplasmonic model. PMID- 26258372 TI - Electro-optical sun compass with a very high degree of accuracy. AB - We present a novel electro-optical solar compass that is able to determine the true North direction with an accuracy better than 1/100 of degree, superior to that of any other magnetic or electronic compass that does not resort to differential GPS. The compass has an electronic sensor to determine the line of sight of the Sun and a simple but effective algorithm to calculate the position of the Sun. The excellent results obtained during the experimental tests demonstrate the advantages of this compass, which is also compact and not expensive. PMID- 26258374 TI - Point-spread function optimization in isoSTED nanoscopy. AB - IsoSTED nanoscopy, a variant of stimulated emission depletion (STED) microscopy, utilizes two opposing objective lenses and features the highest three-dimensional resolution of STED nanoscopes currently available. However, this technique is limited by axially repetitive side minima in the interference pattern of the depletion point-spread function (PSF), which can lead to ghost images. Here, we describe novel strategies to further improve the performance of isoSTED nanoscopy by reshaping the PSF. In particular, we propose employing moderate defocus on the depletion beam to reduce the side minima. Furthermore, we demonstrate a simplified alternative based on objective misalignment and quantitatively compare the expected performance between the two approaches. PMID- 26258375 TI - Yb:fiber laser-based, spectrally coherent and efficient generation of femtosecond 1.3-MUm pulses from a fiber with two zero-dispersion wavelengths. AB - We report, to the best of our knowledge, the first experimental characterization of spectral coherence properties of wavelength conversion inside photonic crystal fibers with two zero-dispersion wavelengths (TZDWs) and demonstrate a low-noise femtosecond 1.3-MUm source employing the TZDW fiber and a 1.3-W, 240-fs Yb:fiber amplifier as the seeding source. Theoretical investigation shows that pulse evolution in our TZDW fiber source is dominated by parametric amplification seeded by self-phase modulation broadening which efficiently converts the pump energy into two new wavelength bands in a deterministic manner, leading to low noise and coherent excitation of femtosecond pulses tunable in the 1.3-MUm spectral region, with up to 3 nJ of pulse energy at 32% of conversion efficiency. PMID- 26258376 TI - Evolution of coherence singularities of Schell-model beams. AB - We show that the propagation of the widely used Schell-model partially coherent light can be easily understood using the ambiguity function. This approach is especially beneficial for the analysis of the mutual intensity of Schell-model beams (SMBs), which are associated with stable coherent beams such as Laguerre-, Hermite-, and Ince-Gaussian. We study the evolution of the coherence singularities during the SMB propagation. It is demonstrated that the distance of singularity formation depends on the coherence degree of the input beam. Moreover, it is proved that the shape, position, and number of singularity curves in far field are defined by the associated coherent beam. PMID- 26258377 TI - Enhanced internal quantum efficiency in non-polar ZnO/Zn0.81Mg0.19O multiple quantum wells by Pt surface plasmons coupling. AB - Non-polar-oriented ZnO/Zn0.81Mg0.19O multiple quantum wells (MQWs) were grown on r-plane sapphire substrates by plasma-assisted molecular beam epitaxy. The internal quantum efficiency (eta(int)) of the non-polar MQWs was only 1.8%. The degraded quality of non-polar MQWs is the main factor for the low eta(int). Besides improving the quality of non-polar MQWs, an effective way to enhance the UV emission of the non-polar MQWs by sputtering Pt nanoparticles has been used. Employing the resonant coupling between UV emission from the MQWs and Pt nanoparticle surface plasmons (SPs), a 20-fold enhancement of the UV emission has been achieved under the optimized sputtering time. Moreover, the eta(int) value of the non-polar MQWs has been strongly improved with the help of Pt. 6.7-fold enhancement of eta(int) has been achieved due to SPs coupling. It paves a new way in designing highly efficient non-polar LEDs. PMID- 26258378 TI - Evaluating multi-exposure speckle imaging estimates of absolute autocorrelation times. AB - Multi-exposure speckle imaging (MESI) is a camera-based flow-imaging technique for quantitative blood-flow monitoring by mapping the speckle-contrast dependence on camera exposure duration. The ability of laser speckle contrast imaging to measure the temporal dynamics of backscattered and interfering coherent fields, in terms of the accuracy of autocorrelation measurements, is a major unresolved issue in quantitative speckle flowmetry. MESI fits for a number of parameters including an estimate of the electric field autocorrelation decay time from the imaged speckles. We compare the MESI-determined correlation times in vitro and in vivo with accepted true values from direct temporal measurements acquired with a photon-counting photon-multiplier tube and an autocorrelator board. The correlation times estimated by MESI in vivo remain on average within 14+/-11% of those obtained from direct temporal autocorrelation measurements, demonstrating that MESI yields highly comparable statistics of the time-varying fields that can be useful for applications seeking not only quantitative blood flow dynamics but also absolute perfusion. PMID- 26258379 TI - Highly efficient plasmonic enhancement of graphene absorption at telecommunication wavelengths. AB - A hybrid graphene system consisting of graphene and silica layers coated on a metal film with groove rings is proposed to strongly enhance light absorption in the graphene layer. Our results indicate that the excited localized plasmon resonance in groove rings can effectively improve the graphene absorption from 2.3% to 43.1%, even to a maximum value of 87.0% in five-layer graphene at telecommunication wavelengths. In addition, the absorption peak is strongly dependent on the groove depth and ring radius as well as the number of graphene layers, enabling the flexible selectivity of both the operating spectral position and bandwidth. This favorable enhancement and tunability of graphene absorption could provide a path toward high-performance graphene opto-electronic components, such as photodetectors. PMID- 26258380 TI - Optical two-tone signal generation without use of optical filter for photonics assisted radio-frequency quadrupling. AB - Optical two-tone (OTT) signal generation is demonstrated without optical wavelength filtering for wavelength-free operation in radio-frequency (RF) upconversion assisted by photonics. This principle is based on selective polarization manipulation for the optical carrier; the optical carrier's polarization is first tilted, and the carrier is then suppressed using a polarizer. Owing to optimized conditions obtained from theoretical calculation and the high polarization extinction ratio achieving a 25.7-dB carrier suppression, a 40-GHz separated OTT signal is successfully generated by an optical intensity modulator driven by a 10-GHz sinusoidal RF signal. Conversion into a frequency-quadrupled RF signal is also demonstrated experimentally. PMID- 26258381 TI - Optoelectronic cross-injection locking of a dual-wavelength photonic integrated circuit for low-phase-noise millimeter-wave generation. AB - We report on the stabilization of a 90-GHz millimeter-wave signal generated from a fully integrated photonic circuit. The chip consists of two DFB single-mode lasers whose optical signals are combined on a fast photodiode to generate a largely tunable heterodyne beat note. We generate an optical comb from each laser with a microwave synthesizer, and by self-injecting the resulting signal, we mutually correlate the phase noise of each DFB and stabilize the beatnote on a multiple of the frequency delivered by the synthesizer. The performances achieved beat note linewidth below 30 Hz. PMID- 26258382 TI - 3-MUm Mid-infrared pulse generation using topological insulator as the saturable absorber. AB - We report an 1150-nm diode-pump passively Q-switched Ho3+-doped ZBLAN fiber laser using topological insulator (TI): Bi2Te3 as the saturable absorber (SA). The TI: Bi2Te3 prepared using the cost-effective hydrothermal intercalation/exfoliation method was dropped onto a CaF2 substrate to fabricate the free-space SA component. It has a low saturable peak intensity of 2.12 MW/cm2 and a high modulation depth of 51.3% measured at 2 MUm. Inserting this component into a linear-cavity Ho3+-doped ZBLAN fiber laser, stable Q-switched pulses at 2979.9 nm were obtained with the repetition rate of 81.96 kHz and pulse duration of 1.37 MUs. The achieved maximum output power and pulse energy were 327.4 mW at a slope efficiency of 11.6% and 3.99 MUJ, respectively, only limited by the available pump power. Our work reveals that the TIs are absolutely a class of promising and reliable SAs for pulse generation at 3-MUm mid-infrared waveband. PMID- 26258383 TI - Polarized backscattering by clusters of spherical particles. AB - The linear and circular polarization ratios for clusters of spherical particles averaged over multiple orientations show a systematic pattern as a function of the refractive index and the size parameter. We show that, at backscattering, the depolarizing behavior of orientation-averaged clusters of spheres can be approximated by second-order scattering of bispheres. The pattern is relatively invariable in terms of the number of particles. We also demonstrate the significance of the near-field effects for polarization at backscattering. PMID- 26258384 TI - Transport of indirect excitons in ZnO quantum wells. AB - We report on spatially- and time-resolved emission measurements and observation of transport of indirect excitons in ZnO/MgZnO wide single quantum wells. PMID- 26258385 TI - Fourier synthesis with single-mode pulses from a multimode laser. AB - Short pulses are generated by mode-locking techniques: amplitude modulation in time domain or frequency modulation in frequency domain. Direct Fourier synthesis of radiation from several single-frequency sources offers an opportunity to generate arbitrary waveforms. Here we report on a new technique of short-pulse synthesis in the Fourier domain. Instead of independent laser sources, we use a single multimode laser with retrieval of its individual cavity modes into a time sequence coherently combined in an external cavity. Combination of 20 consequent single-mode pulses has been performed, demonstrating a new way for arbitrary waveforms synthesis. PMID- 26258386 TI - Continuously tunable modulation scheme for precision control of optical cavities with variable detuning. AB - We present a scheme for locking optical cavities with arbitrary detuning by many linewidths from resonance using an electro-optic modulator that can provide arbitrary ratios of amplitude-to-phase modulation. We demonstrate our scheme on a Fabry-Perot cavity, and show that a well-behaved linear error signal can be obtained by demodulating the reflected light from a cavity that is detuned by several linewidths. PMID- 26258387 TI - Phase-matched electric-field-induced second-harmonic generation in Xe-filled hollow-core photonic crystal fiber. AB - Second-order nonlinearity is induced inside a Xe-filled hollow-core photonic crystal fiber (PCF) by applying an external dc field. The system uniquely allows the linear optical properties to be adjusted by changing the gas pressure, allowing for precise phase matching between the LP01 mode at 1064 nm and the LP02 mode at 532 nm. The dependence of the second-harmonic conversion efficiency on the gas pressure, launched pulse energy, and applied field agrees well with theory. The ultra-broadband guidance offered by anti-resonant reflecting hollow core PCFs, for example, a kagome PCF, offers many possibilities for generating light in traditionally difficult-to-access regions of the electromagnetic spectrum, such as the ultraviolet or the terahertz windows. The system can also be used for noninvasive measurements of the transmission loss in a hollow-core PCF over a broad spectrum, including the deep and vacuum UV regions. PMID- 26258388 TI - Assessing the Utility of Soil DNA Extraction Kits for Increasing DNA Yields and Eliminating PCR Inhibitors from Buried Skeletal Remains. AB - DNA identification of human remains is often necessary when decedents are skeletonized; however, poor DNA recovery and polymerase chain reaction (PCR) inhibition are frequently encountered, a situation exacerbated by burial. In this research, the utility of integrating soil DNA isolation kits into buried skeletal DNA analysis was evaluated and compared to a standard human DNA extraction kit and organic extraction. The soil kits successfully extracted skeletal DNA at quantities similar to standard methods, although the two kits tested, which differ mechanistically, were not equivalent. Further, the PCR inhibitors calcium and humic acid were effectively removed using the soil kits, whereas collagen was less so. Finally, concordant control region sequences were obtained from human skeletal remains using all four methods. Based on these comparisons, soil DNA isolation kits, which quickened the extraction process, proved to be a viable extraction technique for skeletal remains that resulted in positive identification of a decedent. PMID- 26258389 TI - Case-Based Web Learning Versus Face-to-Face Learning: A Mixed-Method Study on University Nursing Students. AB - BACKGROUND: Case-based learning (CBL) is an effective educational method for improving the learning and clinical reasoning skills of students. Advances in e learning technology have supported the development of the Web-based CBL approach to teaching as an alternative or supplement to the traditional classroom approach. PURPOSE: This study aims to examine the CBL experience of Hong Kong students using both traditional classroom and Web-based approaches in undergraduate nursing education. This experience is examined in terms of the perceived self-learning ability, clinical reasoning ability, and satisfaction in learning of these students. METHODS: A mixture of quantitative and qualitative approaches was adopted. All Year-3 undergraduate nursing students were recruited. CBL was conducted using the traditional classroom approach in Semester 1, and the Web-based approach was conducted in Semester 2. Student evaluations were collected at the end of each semester using a self-report questionnaire. In depth, focus-group interviews were conducted at the end of Semester 2. RESULTS: One hundred twenty-two students returned their questionnaires. No difference between the face-to-face and Web-based approaches was found in terms of self learning ability (p = .947), clinical reasoning ability (p = .721), and satisfaction (p = .083). Focus group interview findings complemented survey findings and revealed five themes that reflected the CBL learning experience of Hong Kong students. These themes were (a) the structure of CBL, (b) the learning environment of Web-based CBL, (c) critical thinking and problem solving, (d) cultural influence on CBL learning experience, and (e) student-centered and teacher-centered learning. CONCLUSIONS: The Web-based CBL approach was comparable but not superior to the traditional classroom CBL approach. The Web-based CBL experience of these students sheds light on the impact of Chinese culture on student learning behavior and preferences. PMID- 26258390 TI - Health Promotion Outcomes of a Newly Developed Elastic Band Exercise Program for Older Adults in the Community: A Pilot Test. AB - BACKGROUND: Studies indicate that the incidence of disease, the mortality rate, and medical costs are significantly higher in people aged 65 years and over who do not engage in physical activities than in their peers who do engage in these activities. Therefore, promoting appropriate physical activity among older adults in the community is essential to delaying the health implications of aging. PURPOSE: This pilot test was developed to assess the effectiveness of a newly developed Senior Elastic Band (SEB) exercise program on the health of older adults in community care stations. METHODS: A quasiexperimental design was used. A convenience sample of 20 participants from a community care station was recruited. The SEB intervention included three phases (warm-up, aerobic motion, and static stretching) and was conducted three times per week, 40 minutes per session for 1 month. Twelve health indicators in three categories (functional fitness, self-perceived health status, and sleep quality) were examined before and immediately after 1 month of SEB exercises. RESULTS: Participants showed improved performance at the end of the 1-month study for the following indicators: lung capacity, cardiopulmonary fitness, upper and lower body flexibilities, upper limb muscle power, lower limb muscle endurance, and self perceived physical health status (all ps < .05). No significant differences were identified for the other indicators. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The SEB exercise program shows preliminary and promising effects on improving the health of older adults in a community care station. Healthcare professionals who work with older adults living in the community may consider the SEB exercise program as a health promotion modality to recommend and implement with this population. However, we recommend further testing the long-term effects of this program on a larger population. PMID- 26258391 TI - Establishing the Limits of TrueAllele(r) Casework: A Validation Study. AB - The limits of the expert system, TrueAllele(r) Casework (TA), were explored using challenging mock casework profiles that included 17 single-source and 18 two-, 15 three- and 7 four-person DNA mixtures. The sensitivity (ability to detect a minor contributor) of the TA analysis process was examined by challenging the system with mixture DNA samples that exhibited allelic and locus dropout and other stochastic effects. The specificity (ability to exclude nondonors) was rigorously tested by interrogating TA derived genotypes with 100 nondonor profiles. The accuracy with which TA estimated mixture weights of contributors to the two person mixtures was examined. Finally, first-degree relatives of donors were used to assess the ability of the system to exclude close relatives. TA demonstrated great accuracy, sensitivity, and specificity. TA correctly assigned mixture weights and excluded nearly all first-degree relatives. This study demonstrates the analysis power of the TrueAllele(r) Casework system. PMID- 26258392 TI - Corrigendum. PMID- 26258395 TI - Global Collaboration to Develop New and Existing Drugs for Neonates. PMID- 26258394 TI - No association between mitochondrial DNA copy number and colorectal adenomas. AB - Despite previously reported associations between peripheral blood mtDNA copy number and colorectal cancer, it remains unclear whether altered mtDNA copy number in peripheral blood is a risk factor for colorectal cancer or a biomarker for undiagnosed colorectal cancer. Though colorectal adenomas are well-recognized precursor lesions to colorectal cancer, no study has evaluated an association between mtDNA copy number and colorectal adenoma risk. Hence, we investigated an association between peripheral blood mtDNA copy number and incident, sporadic colorectal adenoma in 412 colorectal adenoma cases and 526 cancer-free controls pooled from three colonoscopy-based case-control studies that used identical methods for case ascertainment, risk factor determination, and biospecimen collection. We also evaluated associations between relative mtDNA copy number and markers of oxidative stress, including circulating F2 -isoprostanes, carotenoids, and fluorescent oxidation products. We measured mtDNA copy number using a quantitative real time polymerase chain reaction (PCR). We used unconditional logistic regression to analyze the association between mtDNA copy number and colorectal adenoma risk after multivariable adjustment. We found no association between logarithmically transformed relative mtDNA copy number, analyzed as a continuous variable, and colorectal adenoma risk (odds ratio = 1.02, 95%CI: 0.82 1.27; P = 0.86). There were no statistically significant associations between relative mtDNA copy number and other markers of oxidative stress. Our findings, taken together with those from previous studies, suggest that relative mtDNA copy number in peripheral blood may more likely be a marker of early colorectal cancer than of risk for the disease or of in vivo oxidative stress. (c) 2015 Wiley Periodicals, Inc. PMID- 26258396 TI - Insights from ENCODE on Missing Proteins: Why beta-Defensin Expression Is Scarcely Detected. AB - beta-Defensins (DEFBs) have a variety of functions. The majority of these proteins were not identified in a recent proteome survey. Neither protein detection nor the analysis of transcriptomic data based on RNA-seq data for three liver cancer cell lines identified any expression products. Extensive investigation into DEFB transcripts in over 70 cell lines offered similar results. This fact naturally begs the question-Why are DEFB genes scarcely expressed? After examining DEFB gene annotation and the physicochemical properties of its protein products, we postulated that regulatory elements could play a key role in the resultant poor transcription of DEFB genes. Four regions containing DEFB genes and six adjacent regions on chromosomes 6, 8, and 20 were carefully investigated using The Encyclopedia of DNA Elements (ENCODE) information, such as that of DNase I hypersensitive sites (DHSs), transcription factors (TFs), and histone modifications. The results revealed that the intensities of these ENCODE features were globally weaker than those in the adjacent regions. Impressively, DEFB-related regions on chromosomes 6 and 8 containing several non-DEFB genes had lower ENCODE feature intensities, indicating that the absence of DEFB mRNAs might not depend on the gene family but may be reliant upon gene location and chromatin structure. PMID- 26258397 TI - Solvation Dynamics in Different Phases of the Lyotropic Liquid Crystalline System. AB - Reverse hexagonal (HII) liquid crystalline material based on glycerol monooleate (GMO) is considered as a potential carrier for drugs and other important biomolecules due to its thermotropic phase change and excellent morphology. In this work, the dynamics of encapsulated water, which plays important role in stabilization and formation of reverse hexagonal mesophase, has been investigated by time dependent Stokes shift method using Coumarin-343 as a solvation probe. The formation of the reverse hexagonal mesophase (HII) and transformation to the L2 phase have been monitored using small-angle X-ray scattering and polarized light microscopy experiments. REES studies suggest the existence of different polar regions in both HII and L2 systems. The solvation dynamics study inside the reverse hexagonal (HII) phase reveals the existence of two different types of water molecules exhibiting dynamics on a 120-900 ps time scale. The estimated diffusion coefficients of both types of water molecules obtained from the observed dynamics are in good agreement with the measured diffusion coefficient collected from the NMR study. The calculated activation energy is found to be 2.05 kcal/mol, which is associated with coupled rotational-translational water relaxation dynamics upon the transition from "bound" to "quasi-free" state. The observed ~2 ns faster dynamics of the L2 phase compared to the HII phase may be associated with both the phase transformation as well as thermotropic effect on the relaxation process. Microviscosities calculated from time-resolved anisotropy studies infer that the interface is almost ~22 times higher viscous than the central part of the cylinder. Overall, our results reveal the unique dynamical features of water inside the cylinder of reverse hexagonal and inverse micellar phases. PMID- 26258398 TI - Delftia tsuruhatensis WGR-UOM-BT1, a novel rhizobacterium with PGPR properties from Rauwolfia serpentina (L.) Benth. ex Kurz also suppresses fungal phytopathogens by producing a new antibiotic-AMTM. AB - The bacterial strain designated as WGR-UOM-BT1 isolated from rhizosphere of Rauwolfia serpentina exhibited broad-spectrum antifungal activity and also improved early plant growth. Based on morphological, biochemical and 16S rRNA gene sequence analyses, the strain BT1 was identified as Delftia tsuruhatensis (KF727978). Under in vitro conditions, the strain BT1 suppressed the growth of wide range of fungal phytopathogens. Purified antimicrobial metabolite from the strain BT1 was identified as nitrogen-containing heterocyclic compound, 'amino(5 (4-methoxyphenyl)-2-methyl-2-(thiophen-2-yl)-2,3-dihydrofuran-3-yl)methanol' (AMTM), with molecular mass of 340*40 and molecular formula of C17 H19 NO3 S. The strain BT1 was positive for rhizosphere colonization (tomato), IAA production, 1 aminocyclopropane-1-carboxylate (ACC) deaminase activity and phosphate solubilization. Under laboratory and greenhouse conditions, the strain BT1 promoted plant growth and suppressed foliar and root fungal pathogens of tomato. Therefore, antimicrobial and disease protection properties of strain BT1 could serve as an effective biological control candidate against devastating fungal pathogens of vegetable plants. Besides, the production of IAA, P solubilization and ACC deaminase activity enhance its potential as a biofertilizer and may stabilize the plant performance under fluctuating environmental conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, we reported that Delftia tsuruhatensis WGR-UOM-BT1 strain has the plant growth promotion activities such as rhizosphere colonization (tomato), IAA production, 1-aminocyclopropane-1 carboxylate (ACC) deaminase activity and phosphate solubilization. This bacterial strain was found producing an antimicrobial nitrogen-containing heterocyclic compound identified as 'amino(5-(4-methoxyphenyl)-2-methyl-2-(thiophen-2-yl)-2,3 dihydrofuran-3-yl)methanol' [C17 H19 NO3 S] (AMTM), which is new to the bacterial world. PMID- 26258399 TI - Test methods and response surface models for hot, humid air decontamination of materials contaminated with dirty spores of Bacillus anthracis ?Sterne and Bacillus thuringiensis Al Hakam. AB - AIMS: To develop test methods and evaluate survival of Bacillus anthracis ?Sterne or Bacillus thuringiensis Al Hakam on materials contaminated with dirty spore preparations after exposure to hot, humid air using response surface modelling. METHODS AND RESULTS: Spores (>7 log10 ) were mixed with humic acid + spent sporulation medium (organic debris) or kaolin (dirt debris). Spore samples were then dried on five different test materials (wiring insulation, aircraft performance coating, anti-skid, polypropylene, and nylon). Inoculated materials were tested with 19 test combinations of temperature (55, 65, 75 degrees C), relative humidity (70, 80, 90%) and time (1, 2, 3 days). The slowest spore inactivation kinetics was on nylon webbing and/or after addition of organic debris. CONCLUSIONS: Hot, humid air effectively decontaminates materials contaminated with dirty Bacillus spore preparations; debris and material interactions create complex decontamination kinetic patterns; and B. thuringiensis Al Hakam is a realistic surrogate for B. anthracis. SIGNIFICANCE AND IMPACT OF THE STUDY: Response surface models of hot, humid air decontamination were developed which may be used to select decontamination parameters for contamination scenarios including aircraft. PMID- 26258400 TI - Religion, spirituality, and health outcomes in cancer: A case for a meta-analytic investigation. AB - A growing body of research shows that a majority of patients with cancer report having religious and spiritual (R/S) beliefs, engaging in R/S behaviors, or deriving comfort from R/S experiences. These studies have been reviewed but not subjected to rigorous critical analysis. A meta-analytic approach is needed to provide a more definitive understanding of the relationships between R/S (affective, behavioral, and cognitive dimensions) and physical, mental, and social health in all phases of cancer including diagnosis, treatment, survivorship, and palliative care. A meta-analysis can quantify the degree of association between R/S dimensions and patient-reported health outcomes and the conditions under which these associations are strengthened or attenuated. Results can, in turn, help focus future work in this area by highlighting key variables for inclusion in studies of R/S and cancer and identifying particular subgroups for whom dimensions of R/S are particularly important to their health. PMID- 26258401 TI - Patients With Ankylosing Spondylitis Have Increased Cardiovascular and Cerebrovascular Mortality: A Population-Based Study. AB - BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory arthritis affecting the spine in young adults. It is associated with excess cardiovascular and cerebrovascular morbidity. OBJECTIVE: To determine whether patients with AS are at increased risk for cardiovascular and cerebrovascular mortality. DESIGN: Population-based retrospective cohort study using administrative health data. SETTING: Ontario, Canada. PATIENTS: 21 473 patients with AS aged 15 years or older and 86 606 comparators without AS, matched for age, sex, and location of residence. MEASUREMENTS: The primary outcome was a composite of cardiovascular and cerebrovascular death. Hazard ratios (HRs) for vascular death were calculated; adjusted for history of cancer, diabetes, dementia, inflammatory bowel disease, hypertension, chronic kidney disease, and peripheral vascular disease; and, among those aged 66 years or older, relevant drug therapies. Independent risk factors for vascular mortality were identified in patients with AS. RESULTS: The mean age of patients with AS was 46 years, and 53% were male. Patients and comparators were followed for 166 920 and 686 461 patient-years, respectively. Adjusted HRs for vascular death in AS were 1.36 (95% CI, 1.13 to 1.65) overall, 1.46 (CI, 1.13 to 1.87) in men, and 1.24 (CI, 0.92 to 1.67) in women. Significant risk factors for vascular death were age; male sex; lower income; dementia; chronic kidney disease; peripheral vascular disease; and, among patients aged 65 years or older, lack of exposure to nonsteroidal anti inflammatory drugs and statins. LIMITATION: Diagnosis codes for AS were not validated in Ontario. CONCLUSION: Ankylosing spondylitis is associated with increased risk for vascular mortality. A comprehensive strategy to screen and treat modifiable vascular risk factors in AS is needed. PRIMARY FUNDING SOURCE: The Arthritis Program, University Health Network, Toronto; and The Arthritis Society, Canada. PMID- 26258402 TI - On the accuracy of viscous and turbulent loss quantification in stenotic aortic flow using phase-contrast MRI. AB - PURPOSE: To investigate the limits of phase contrast MRI (PC-MRI)-based measurements of viscous losses and turbulent kinetic energy (TKE) pertaining to spatial resolution, signal-to-noise ratio (SNR), and non-Gaussian intravoxel velocity distributions. THEORY AND METHODS: High-resolution particle tracking velocimetry data obtained in a realistic aortic phantom with stenotic flow were used to simulate PC-MRI measurements at different resolutions and noise levels. Laminar viscous losses were computed using the spatial gradients of the mean velocity vector field, and TKE levels were derived based on the intravoxel phase dispersion of flow-sensitized PC-MRI measurements. RESULTS: Increasing the voxel size from 0.625 to 2.5 mm resulted in an underestimation of viscous losses of up to 83%, whereas total TKE values showed errors of <15% and reduced sensitivity to voxel size. Relative errors in viscous loss quantification were found to be less dependent on noise levels when compared with TKE values. In general, a SNR of 20 30 is required for both methods. CONCLUSION: At spatial resolutions feasible in clinical three-dimensional PC-MRI measurements, viscous losses of stenotic flows are significantly underestimated, whereas TKE shows smaller errors and reduced sensitivity to spatial resolution. Magn Reson Med 76:191-196, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26258403 TI - The Use of Femoral Neck Axis Length to Estimate Sex and Ancestry. AB - Having multiple reliable methods of estimating sex and ancestry from various skeletal features increases the likelihood of identifying skeletal remains. Femoral neck axis length (FNAL), as measured in living individuals, has been shown to vary by sex and ancestry. FNAL has not, however, been previously measured directly from skeletonized remains and investigated for its potential use in forensic anthropological applications. This research proposes a method for measuring FNAL from skeletal remains, determines the reliability and repeatability of the measurement, and assesses the validity of FNAL in sex and ancestry estimation. Results showed low interobserver error in the measurement of FNAL (TEM=0.33 mm, R=0.99). Significant differences in FNAL were found between sexes as well as between American Black, American White, and Native American groups. FNAL can correctly classify sex in ~86% of all cases and is considered valuable to sex estimation. The value of FNAL to ancestry estimation, however, is considered limited. PMID- 26258404 TI - Complexes of DNA with the Antimicrobial Peptide LL37 Augment NK Cell Functions by Inducing Type I Interferon Production from Circulating Monocytes and Plasmacytoid Predendritic Cells. AB - The cationic antimicrobial peptide, LL37, forms electrostatic complexes with DNA (LL37-DNA), which are potent activators of circulating plasmacytoid predendritic cells (ppDCs) and monocytes. However, the effects of LL37-DNA on other immune cell types, such as NK cells, are poorly characterized. In this study, we show that complexes of human genomic DNA (hgDNA) or synthetic double-stranded oligodeoxynucleotides with LL37 strongly enhance natural cytotoxicity of human peripheral blood mononuclear cells (PBMCs) upon an overnight culture, whereas hgDNA alone has no effect, and LL37 alone is moderately active. LL37-DNA complexes potentiate degranulation of, and interferon (IFN)-gamma production by, NK cells upon subsequent encounter of K562 target cells. The complexes do not influence percentages of NK cells among PBMCs or the expression of cytotoxic proteins by NK cells. Using neutralizing anticytokine antibodies and immunomagnetic depletion of different subpopulations of PBMCs, we found that the effect of LL37-DNA on NK cells is indirect and mediated by type I IFNs produced by monocytes and, to a lesser extent, by ppDCs. We discuss possible roles of LL37 DNA complexes in the regulation of NK cell functions and in the treatment of cancer. PMID- 26258405 TI - Endoscopic management of colonic diverticular bleeding. AB - Colonic diverticular bleeding is the most common cause of lower gastrointestinal bleeding. Colonoscopy can be used for both diagnosis and treatment of colonic diverticular bleeding. Identification of the stigmata of recent hemorrhage allows for various endoscopic hemostasis methods. Clipping, endoscopic band ligation, injection therapy, and thermal contact are available methods for endoscopic hemostasis. However, the optimal technique remains to be determined. Herein, we review the techniques and clinical outcomes of endoscopic hemostasis for colonic diverticular bleeding. PMID- 26258406 TI - Undermeasuring Overuse--An Examination of National Clinical Performance Measures. PMID- 26258407 TI - Identification of Novel Biomarkers for Metastatic Colorectal Cancer Using Angiogenesis-Antibody Array and Intracellular Signaling Array. AB - Colorectal cancer (CRC) is one of the three leading causes for cancer mortality. CRC kills over 600,000 people annually worldwide. The most common cause of death from CRC is the metastasis to distant organs. However, biomarkers for CRC metastasis remain ill-defined. We compared primary and metastatic CRC cell lines for their angiogenesis-protein profiles and intracellular signaling profiles to identify novel biomarkers for CRC metastasis. To this end, we used primary and metastatic CRC cell lines as a model system and normal human colon cell line as a control. The angiogenesis profiles two isogenic CRC cell lines, SW480 and SW620, and HT-29 and T84 revealed that VEGF was upregulated in both SW620 and T84 whereas coagulation factor III, IGFBP-3, DPP IV, PDGF AA/AB, endothelin I and CXCL16 were downregulated specifically in metastatic cell lines. Furthermore, we found that TIMP-1, amphiregulin, endostatin, angiogenin were upregulated in SW620 whereas downregulated in T84. Angiogenin was downregulated in T84 and GM-CSF was also downregulated in SW620. To induce CRC cell metastasis, we treated cells with pro-inflammatory cytokine IL-6. Upon IL-6 treatment, epithelial-mesenchymal transition was induced in CRC cells. When DLD-1 and HT-29 cells were treated with IL-6; Akt, STAT3, AMPKalpha and Bad phosphorylation levels were increased. Interestingly, SW620 showed the same signal activation pattern with IL-6 treatment of HT-29 and DLD-1. Our data suggest that Akt, STAT3, AMPKalpha and Bad activation can be biomarkers for metastatic colorectal cancer. IL-6 treatment specifically reduced phosphorylation levels of EGFR, HER2 receptor, Insulin R and IGF-1R in receptor tyrosine kinase array study with HT-29. Taken together, we have identified novel biomarkers for metastatic CRC through the angiogenesis antibody array and intracellular signaling array studies. Present study suggests that those novel biomarkers can be used as CRC prognosis biomarkers, and as potential targets for the metastatic CRC therapy. PMID- 26258408 TI - Alteration in metabolic signature and lipid metabolism in patients with angina pectoris and myocardial infarction. AB - Lipid metabolites are indispensable regulators of physiological and pathological processes, including atherosclerosis and coronary artery disease (CAD). However, the complex changes in lipid metabolites and metabolism that occur in patients with these conditions are incompletely understood. We performed lipid profiling to identify alterations in lipid metabolism in patients with angina and myocardial infarction (MI). Global lipid profiling was applied to serum samples from patients with CAD (angina and MI) and age-, sex-, and body mass index matched healthy subjects using ultra-performance liquid chromatography/quadruple time-of-flight mass spectrometry and multivariate statistical analysis. A multivariate analysis showed a clear separation between the patients with CAD and normal controls. Lysophosphatidylcholine (lysoPC) and lysophosphatidylethanolamine (lysoPE) species containing unsaturated fatty acids and free fatty acids were associated with an increased risk of CAD, whereas species of lysoPC and lyso-alkyl PC containing saturated fatty acids were associated with a decreased risk. Additionally, PC species containing palmitic acid, diacylglycerol, sphingomyelin, and ceramide were associated with an increased risk of MI, whereas PE-plasmalogen and phosphatidylinositol species were associated with a decreased risk. In MI patients, we found strong positive correlation between lipid metabolites related to the sphingolipid pathway, sphingomyelin, and ceramide and acute inflammatory markers (high-sensitivity C reactive protein). The results of this study demonstrate altered signatures in lipid metabolism in patients with angina or MI. Lipidomic profiling could provide the information to identity the specific lipid metabolites under the presence of disturbed metabolic pathways in patients with CAD. PMID- 26258409 TI - The Role of Liver in Determining Serum Colon-Derived Uremic Solutes. AB - Evidence has shown that indoxyl sulfate (IS) and p-cresyl sulfate (PCS) may be alternative predictors of clinical outcomes in chronic kidney disease (CKD). Both toxins are derived from the gastrointestinal tract and metabolised in the liver. However, it is unclear whether the liver affects the production of IS and PCS. Here, we explore the association between IS and PCS levels in liver cirrhosis and a CKD-based cohort (N = 115). Liver and kidney function was assessed and classified by a Child-Pugh score (child A-C) and a modified version of the Modification of Diet in Renal Disease (MDRD) equation (Stages 1-4), respectively. An animal model was also used to confirm the two toxin levels in a case of liver fibrosis. In patients with early liver cirrhosis (child A), IS and PCS were significantly associated with CKD stages. In contrast, serum IS and PCS did not significantly change in advanced liver cirrhosis (child C). A stepwise multiple linear regression analysis also showed that T-PCS was significantly associated with stages of liver cirrhosis after adjusting for other confounding factors (B = -2.29, p = 0.012). Moreover, the serum and urine levels of T-PCS and T-IS were significantly lower in rats with liver failure than in those without (p<0.01, p<0.05 and p<0.01, p<0.05, respectively). These results indicated that in addition to the kidneys, the liver was an essential and independent organ in determining serum IS and PCS levels. The production rate of IS and PCS was lower in patients with advanced liver cirrhosis. PMID- 26258410 TI - An Economic Evaluation of Neonatal Screening for Inborn Errors of Metabolism Using Tandem Mass Spectrometry in Thailand. AB - BACKGROUND: Inborn errors of metabolism (IEM) are a rare group of genetic diseases which can lead to several serious long-term complications in newborns. In order to address these issues as early as possible, a process called tandem mass spectrometry (MS/MS) can be used as it allows for rapid and simultaneous detection of the diseases. This analysis was performed to determine whether newborn screening by MS/MS is cost-effective in Thailand. METHOD: A cost-utility analysis comprising a decision-tree and Markov model was used to estimate the cost in Thai baht (THB) and health outcomes in life-years (LYs) and quality adjusted life year (QALYs) presented as an incremental cost-effectiveness ratio (ICER). The results were also adjusted to international dollars (I$) using purchasing power parities (PPP) (1 I$ = 17.79 THB for the year 2013). The comparisons were between 1) an expanded neonatal screening programme using MS/MS screening for six prioritised diseases: phenylketonuria (PKU); isovaleric acidemia (IVA); methylmalonic acidemia (MMA); propionic acidemia (PA); maple syrup urine disease (MSUD); and multiple carboxylase deficiency (MCD); and 2) the current practice that is existing PKU screening. A comparison of the outcome and cost of treatment before and after clinical presentations were also analysed to illustrate the potential benefit of early treatment for affected children. A budget impact analysis was conducted to illustrate the cost of implementing the programme for 10 years. RESULTS: The ICER of neonatal screening using MS/MS amounted to 1,043,331 THB per QALY gained (58,647 I$ per QALY gained). The potential benefits of early detection compared with late detection yielded significant results for PKU, IVA, MSUD, and MCD patients. The budget impact analysis indicated that the implementation cost of the programme was expected at approximately 2,700 million THB (152 million I$) over 10 years. CONCLUSION: At the current ceiling threshold, neonatal screening using MS/MS in the Thai context is not cost-effective. However, the treatment of patients who were detected early for PKU, IVA, MSUD, and MCD, are considered favourable. The budget impact analysis suggests that the implementation of the programme will incur considerable expenses under limited resources. A long-term epidemiological study on the incidence of IEM in Thailand is strongly recommended to ascertain the magnitude of problem. PMID- 26258411 TI - Epigenetic silencing of ITGA2 by MiR-373 promotes cell migration in breast cancer. AB - The loss of ITGA2 plays an important role in cancer metastasis in several solid cancers. However, the molecular mechanism of ITGA2 loss in primary cancers remains unclear. In this study, we found that a lower ITGA2 protein level was observed in breast cancers compared to adjacent non-cancerous breast tissues. Interestingly, the reduction degree of ITGA2 at the protein level was far more than that at the mRNA level. We further showed that the translation of ITGA2 mRNA was directly inhibited by miR-373 through binding to ITGA2-3'UTR. Silencing of ITGA2 detached cell-cell interactions, induced the deploymerization of stress fiber F-actin and stimulated cancer cell migration, similar to the effect of miR 373 over-expression. The co-expression of ITGA2, not ITGA2-3'UTR, could abrogate miR-373-induced cancer cell migration because that the expression of ITGA2-3'UTR was inhibited by co-transfected miR-373. ITGA2 protein level was inversely associated with miR-373 level in breast cancers (r = -0.663, P<0.001). 73.33% of breast cancer patients with high miR-373 and low ITGA2 expression exhibited the lymph node-positive metastases. Together, our results show that epigenetic silencing of ITGA2 by miR-373 stimulates breast cancer migration, and miR 373high/ITGA2low may be as a prognosis biomarker for breast cancer patients. PMID- 26258412 TI - Tumor neoantigens: building a framework for personalized cancer immunotherapy. AB - It is now well established that the immune system can recognize developing cancers and that therapeutic manipulation of immunity can induce tumor regression. The capacity to manifest remarkably durable responses in some patients has been ascribed in part to T cells that can (a) kill tumor cells directly, (b) orchestrate diverse antitumor immune responses, (c) manifest long lasting memory, and (d) display remarkable specificity for tumor-derived proteins. This specificity stems from fundamental differences between cancer cells and their normal counterparts in that the former develop protein-altering mutations and undergo epigenetic and genetic alterations, resulting in aberrant protein expression. These events can result in formation of tumor antigens. The identification of mutated and aberrantly expressed self-tumor antigens has historically been time consuming and laborious. While mutant antigens are usually expressed in a tumor-specific manner, aberrantly expressed antigens are often shared between cancers and, therefore, in the past, have been the major focus of therapeutic cancer vaccines. However, advances in next-generation sequencing and epitope prediction now permit the rapid identification of mutant tumor neoantigens. This review focuses on a discussion of mutant tumor neoantigens and their use in personalizing cancer immunotherapies. PMID- 26258413 TI - Restoration of Na+/H+ exchanger NHE3-containing macrocomplexes ameliorates diabetes-associated fluid loss. AB - Diarrhea is one of the troublesome complications of diabetes, and the underlying causes of this problem are complex. Here, we investigated whether altered electrolyte transport contributes to diabetic diarrhea. We found that the expression of Na+/H+ exchanger NHE3 and several scaffold proteins, including NHE3 regulatory factors (NHERFs), inositol trisphosphate (IP3) receptor-binding protein released with IP3 (IRBIT), and ezrin, was decreased in the intestinal brush border membrane (BBM) of mice with streptozotocin-induced diabetes. Treatment of diabetic mice with insulin restored intestinal NHE3 activity and fluid absorption. Molecular analysis revealed that NHE3, NHERF1, IRBIT, and ezrin form macrocomplexes, which are perturbed under diabetic conditions, and insulin administration reconstituted these macrocomplexes and restored NHE3 expression in the BBM. Silencing of NHERF1 or IRBIT prevented NHE3 trafficking to the BBM and insulin-dependent NHE3 activation. IRBIT facilitated the interaction of NHE3 with NHERF1 via protein kinase D2-dependent phosphorylation. Insulin stimulated ezrin phosphorylation, which enhanced the interaction of ezrin with NHERF1, IRBIT, and NHE3. Additionally, oral administration of lysophosphatidic acid (LPA) increased NHE3 activity and fluid absorption in diabetic mice via an insulin-independent pathway. Together, these findings indicate the importance of NHE3 in diabetic diarrhea and suggest LPA administration as a potential therapeutic strategy for management of diabetic diarrhea. PMID- 26258414 TI - Arginine methyltransferase PRMT5 is essential for sustaining normal adult hematopoiesis. AB - Epigenetic regulators play critical roles in normal hematopoiesis, and the activity of these enzymes is frequently altered in hematopoietic cancers. The major type II protein arginine methyltransferase PRMT5 catalyzes the formation of symmetric dimethyl arginine and has been implicated in various cellular processes, including pluripotency and tumorigenesis. Here, we generated Prmt5 conditional KO mice to evaluate the contribution of PRMT5 to adult hematopoiesis. Loss of PRMT5 triggered an initial but transient expansion of hematopoietic stem cells (HSCs); however, Prmt5 deletion resulted in a concurrent loss of hematopoietic progenitor cells (HPCs), leading to fatal BM aplasia. PRMT5 specific effects on hematopoiesis were cell intrinsic and depended on PRMT5 methyltransferase activity. We found that PRMT5-deficient hematopoietic stem and progenitor cells exhibited severely impaired cytokine signaling as well as upregulation of p53 and expression of its downstream targets. Together, our results demonstrate that PRMT5 plays distinct roles in the behavior of HSCs compared with HPCs and is essential for the maintenance of adult hematopoietic cells. PMID- 26258415 TI - A molecular trigger for intercontinental epidemics of group A Streptococcus. AB - The identification of the molecular events responsible for strain emergence, enhanced virulence, and epidemicity has been a long-pursued goal in infectious diseases research. A recent analysis of 3,615 genomes of serotype M1 group A Streptococcus strains (the so-called "flesh-eating" bacterium) identified a recombination event that coincides with the global M1 pandemic beginning in the early 1980s. Here, we have shown that the allelic variation that results from this recombination event, which replaces the chromosomal region encoding secreted NADase and streptolysin O, is the key driver of increased toxin production and enhanced infection severity of the M1 pandemic strains. Using isoallelic mutant strains, we found that 3 polymorphisms in this toxin gene region increase resistance to killing by human polymorphonuclear leukocytes, increase bacterial proliferation, and increase virulence in animal models of pharyngitis and necrotizing fasciitis. Genome sequencing of an additional 1,125 streptococcal strains and virulence studies revealed that a highly similar recombinational replacement event underlies an ongoing intercontinental epidemic of serotype M89 group A Streptococcus infections. By identifying the molecular changes that enhance upper respiratory tract fitness, increased resistance to innate immunity, and increased tissue destruction, we describe a mechanism that underpins epidemic streptococcal infections, which have affected many millions of people. PMID- 26258417 TI - Rapamycin improves TIE2-mutated venous malformation in murine model and human subjects. AB - Venous malformations (VMs) are composed of ectatic veins with scarce smooth muscle cell coverage. Activating mutations in the endothelial cell tyrosine kinase receptor TIE2 are a common cause of these lesions. VMs cause deformity, pain, and local intravascular coagulopathy, and they expand with time. Targeted pharmacological therapies are not available for this condition. Here, we generated a model of VMs by injecting HUVECs expressing the most frequent VM causing TIE2 mutation, TIE2-L914F, into immune-deficient mice. TIE2-L914F expressing HUVECs formed VMs with ectatic blood-filled channels that enlarged over time. We tested both rapamycin and a TIE2 tyrosine kinase inhibitor (TIE2 TKI) for their effects on murine VM expansion and for their ability to inhibit mutant TIE2 signaling. Rapamycin prevented VM growth, while TIE2-TKI had no effect. In cultured TIE2-L914F-expressing HUVECs, rapamycin effectively reduced mutant TIE2-induced AKT signaling and, though TIE2-TKI did target the WT receptor, it only weakly suppressed mutant-induced AKT signaling. In a prospective clinical pilot study, we analyzed the effects of rapamycin in 6 patients with difficult-to-treat venous anomalies. Rapamycin reduced pain, bleeding, lesion size, functional and esthetic impairment, and intravascular coagulopathy. This study provides a VM model that allows evaluation of potential therapeutic strategies and demonstrates that rapamycin provides clinical improvement in patients with venous malformation. PMID- 26258418 TI - Maternal functional hemodynamics in the second half of pregnancy: a longitudinal study. AB - OBJECTIVE: Cardiovascular response to passive leg raising (PLR) is useful in assessing preload reserve, but it has not been studied longitudinally during pregnancy. We aimed to investigate gestational age associated serial changes in maternal functional hemodynamics and establish longitudinal reference ranges for the second half of pregnancy. MATERIALS AND METHODS: This was a prospective longitudinal study on 98 healthy pregnant women who were examined 3-5 times during 20-40 weeks of gestation (a total of 441 observations). Maternal cardiac function and systemic hemodynamics were assessed at baseline and 90 seconds after PLR using impedance cardiography (ICG). The main outcome measures were gestational age specific changes in ICG-derived variables of maternal cardiovascular function and functional hemodynamic response to PLR. RESULTS: Hemodynamic response to PLR varied during pregnancy. PLR led to an insignificant increase in stroke volume during 20+0 to 31+6 weeks, but later in gestation the stroke volume was slightly lower at PLR compared to baseline. PLR caused no significant change in cardiac output between 20+0 and 23+6 weeks and a significant decrease after 24+0 weeks. A decrease in heart rate, mean arterial pressure, and cardiac contractility was observed during PLR throughout the second half of pregnancy. Systemic vascular resistance was reduced by PLR up to 32+0 weeks, but increased slightly thereafter. CONCLUSION: Healthy pregnant women appear to have limited preload reserve and reduced cardiac contractility, especially in the third trimester, which makes them vulnerable to fluid overload and cardiac failure. PMID- 26258419 TI - [The Austrian LEAD (Lung hEart sociAL boDy) Study: Background of the Austrian Longitudinal Cohort Study]. AB - More research is needed to elucidate natural history and underlying pathomechanisms of the most common airway diseases, Asthma and COPD. In the last decade risk factors affecting the natural history of lung function, defined by the decline of lung function over time, have been evaluated. Moreover, scientific methods have been extended and novel biomarkers, genetics, metabolomics, and epidemiology are dominant tools for investigating the natural history of lung function and potential risk factors. Evidence shows that lung function in childhood is a predictor for lung function in adulthood and risk factors starting in utero contribute to lung function decline during life. Therefore, recently it has been hypothesized that COPD begins in childhood. Thus, prospective investigation of lung function changes including novel scientific methodology has been advocated. The Austrian LEAD study has been initiated in the general population 2012 to investigate the natural history of obstructive airway diseases. PMID- 26258416 TI - Reversal of microRNA-150 silencing disadvantages crizotinib-resistant NPM-ALK(+) cell growth. AB - The regulatory microRNA miR-150 is involved in the development of hemopathies and is downregulated in T-lymphomas, such as anaplastic large-cell lymphoma (ALCL) tumors. ALCL is defined by the presence or absence of translocations that activate the anaplastic lymphoma kinase (ALK), with nucleophosmin-ALK (NPM-ALK) fusions being the most common. Here, we compared samples of primary NPM-ALK(+) and NPM-ALK(-) ALCL to investigate the role of miR-150 downstream of NPM-ALK. Methylation of the MIR150 gene was substantially elevated in NPM-ALK(+) biopsies and correlated with reduced miR-150 expression. In NPM-ALK(+) cell lines, DNA hypermethylation-mediated miR-150 repression required ALK-dependent pathways, as ALK inhibition restored miR-150 expression. Moreover, epigenetic silencing of miR 150 was due to the activation of STAT3, a major downstream substrate of NPM-ALK, in cooperation with DNA methyltransferase 1 (DNMT1). Accordingly, miR-150 repression was turned off following treatment with the DNMT inhibitor, decitabine. In murine NPM-ALK(+) xenograft models, miR-150 upregulation induced antineoplastic activity. Treatment of crizotinib-resistant NPM-ALK(+) KARPAS-299 CR06 cells with decitabine or ectopic miR-150 expression reduced viability and growth. Altogether, our results suggest that hypomethylating drugs, alone or in combination with other agents, may benefit ALK(+) patients harboring tumors resistant to crizotinib and other anti-ALK tyrosine kinase inhibitors (TKIs). Moreover, these results support further work on miR-150 in these and other ALK(+) malignancies. PMID- 26258420 TI - [Differential Treatment Strategy of Pleural Empyema in a Post-Pneumonectomy Cavity]. AB - INTRODUCTION: Pleural empyema in a post-pneumonectomy cavity (PEC) occurs with a frequency of 2% -15% and a mortality of more than 10%. It can occur with or without bronchopleural fistula (BPF). The treatment of empyema in the PEC requires a strict algorithm: drainage, bronchoscopy, closure of the fistula, thorough cleaning of the PEC, filling the cavity, thoracoplasty. METHODS: 39 cases with an empyema in the PEC were analysed retrospectively (men: n = 38; women: n = 1; mean age: 60.3 +/- 7.6 years). In 32 (82.1%) of the patients, a BPF was detected (right: n = 26, left: n = 6). The average length of stay in hospital was 125 days (22 - 293 days). Cleaning of the PEC was achieved in all surviving patients (n = 23, 65.1%). All patients (n = 39) underwent bronchoscopy with placement of a chest tube for drainage. The BPF was closed in three cases (7.7%) with a stent while in 12 cases (30.8%) a vascularized flap was used. In 14 patients (35.9%) the bronchial stump was either reclosed with sutures or resected. In three cases (7.7%) a re-anastomosis was performed. RESULTS: The PEC became sterile by regular flushing with antibiotic solution in three patients (7.7%). In 35.9% of the patients (n = 14), aggressive surgical debridement (Weder procedure) was necessary. A thoracic window was applied in 22 patients (56.4%), followed by negative pressure wound therapy (NPWT) and change of dressing every three to four days or a tamponade of the thoracic cavity with simple dressings. In 19 patients (48.7%) the thoracic cavity was sealed with an antibiotic solution. In 5 cases an Alexander thoracoplasty took place. CONCLUSIONS: Pleural empyema after pneumonectomy still poses a serious postoperative complication. A bronchopleural fistula is often detected. Thus, two problems arise at the same time - fistula and infection in the pleural cavity. Through a strict algorithm, both problems can be dealt with in stages. After sealing the fistula, the thoracic cavity is thoroughly cleaned and finally the thorax is closed. Only in a small number of patients (1.3%) in whom these measures remain ineffective (persistent MRSA, aspergillus colonization) should the cavity be obliterated by thoracoplasty. PMID- 26258421 TI - [Pilot Project: Improved Lung Deposition via a New Nasal Inhalation Procedure]. AB - INTRODUCTION: Inhaled drugs can only be effective if they reach the middle and small airways. This study introduces a system that combines a trans-nasal application of aerosols with noninvasive pressure support ventilation. METHODS: In a pilot study, 7 COPD patients with GOLD stages II and III inhaled a radiolabeled marker dissolved in water via a trans-nasal route. The mean aerosol particle size was 5.5 um. Each patient took part in two inhalation sessions that included two application methods and were at least 70 hours apart. During the first session ("passive method"), the patient inhaled the aerosol through an open tube system. The second session ("active method") included pressure support ventilation during the inhalation process. A gamma camera and planar scintigraphy was used to determine the distribution of aerosol particles in the patient's body and lung. RESULTS: The pressure supported inhalation ("active method") results in an increased aerosol lung deposition compared to the passive method. Above all, we could demonstrate deposition in the lung periphery with relatively large aerosol particles (5.5 um). DISCUSSION: The results prove that the combination of trans-nasal inhalation with noninvasive pressure support ventilation leads to significantly increased particle deposition in the lung. PMID- 26258422 TI - [ROS1-Translocations in Non-Small Cell Lung Cancer]. AB - AIM: Summary of prevalence, testing and treatment approaches in patients with non small cell lung cancer (NSCLC) and ROS1 activation. METHODS: Internet-based search for clinical and preclinical studies as well as search for ongoing studies in web-based databases. RESULTS: ROS1 translocations lead to tyrosine kinase activation and can be detected in 1 - 2% of all NSCLC and in 3 - 6% of pulmonary adenocarcinoma patients, respectively, using in situ hybridization techniques. RESULTS from phase I clinical studies using the ROS1 inhibitor crizotinib indicate response rates of 70 - 80% and a median progression-free survival of about 19 months. The therapy was generally well tolerated. CONCLUSIONS: NSCLC harbouring ROS1-translocations can be treated with targeted therapy leading to promising response and survival in patients. Hence, these alterations should be included into current molecular testing panels in stage IV pulmonary adenocarcinomas. PMID- 26258423 TI - Evaluation of pain sensitivity by tender point counts and myalgic score in patients with and without obstructive sleep apnea syndrome. AB - AIM: The purpose of this study was to assess the difference between patients with and without obstructive sleep apnea syndrome (OSAS) with respect to pain sensitivity. METHOD: The study was conducted on 31 womens diagnosed with OSAS and 31 healthy women. All patients underwent polysomnographic testing. A pressure algometer (dolorimeter) was used to measure the pressure pain threshold. Fibromyalgia was diagnosed based on the 1990 American College of Rheumatology diagnosis criteria. RESULTS: The myalgic score was 73.95 +/- 18.09 in patients with OSAS, while this value was 84.18 +/- 24.31 in the control group. The difference between the groups was statistically significant (P = 0.041).The number of tender points was 8.19 +/- 3.35 in the patient group with OSAS, while this number was 6.35 +/- 2.23 in the control group. The difference between the two groups was statistically significant (P = 0.014). No statistically significant differences were found between age, body mass index, Beck depression scores, control point score and the presence of fibromyalgia, between the two groups (P > 0.05). A statistically significant positive correlation was found between the myalgic scores and mean saturation O2 (%) values of the patients (r = 0.357; P = 0.049). CONCLUSION: The differences noted between OSAS patients and the control group with respect to myalgic score and the number of tender points suggest that there might be a relation between OSAS and pain sensitivity. There might be an association between low oxygen saturation and total myalgic score. PMID- 26258424 TI - Cell surface expression level variation between two common Human Leukocyte Antigen alleles, HLA-A2 and HLA-B8, is dependent on the structure of the C terminal part of the alpha 2 and the alpha 3 domains. AB - Constitutive cell surface expression of Human Leukocyte Antigen (HLA) class I antigens vary extremely from tissue to tissue and individual antigens may differ widely in expression levels. Down-regulation of class I expression is a known immune evasive mechanism used by cancer cells and viruses. Moreover, recent observations suggest that even minor differences in expression levels may influence the course of viral infections and the frequency of complications to stem cell transplantation. We have shown that some human multipotent stem cells have high expression of HLA-A while HLA-B is only weakly expressed, and demonstrate here that this is also the case for the human embryonic kidney cell line HEK293T. Using quantitative flow cytometry and quantitative polymerase chain reaction we found expression levels of endogenous HLA-A3 (median 71,204 molecules per cell) 9.2-fold higher than the expression of-B7 (P = 0.002). Transfection experiments with full-length HLA-A2 and -B8 encoding plasmids confirmed this (54,031 molecules per cell vs. 2,466, respectively, P = 0.001) independently of transcript levels suggesting a post-transcriptional regulation. Using chimeric constructs we found that the cytoplasmic tail and the transmembrane region had no impact on the differential cell surface expression. In contrast, ~65% of the difference could be mapped to the six C-terminal amino acids of the alpha 2 domain and the alpha 3 domain (amino acids 176-284), i.e. amino acids not previously shown to be of importance for differential expression levels of HLA class I molecules. We suggest that the differential cell surface expression of two common HLA-A and-B alleles is regulated by a post-translational mechanism that may involve hitherto unrecognized molecules. PMID- 26258426 TI - Lattice Breathing Inhibited Layered Vanadium Oxide Ultrathin Nanobelts for Enhanced Sodium Storage. AB - Operating as the "rocking-chair" battery, sodium ion battery (SIB) with acceptable high capacity is a very promising energy storage technology. Layered vanadium oxide xerogel exhibits high sodium storage capacity. But it undergoes large lattice breathing during sodiation/desodiation, resulting in fast capacity fading. Herein, we develop a facile hydrothermal method to synthesize iron preintercalated vanadium oxide ultrathin nanobelts (Fe-VOx) with constricted interlayer spacing. Using the Fe-VOx as cathode for SIB, the lattice breathing during sodiation/desodiation is largely inhibited and the interlayer spacing is stabilized for reversible and rapid Na(+) insertion/extraction, displaying enhanced cycling and rate performance. This work presents a new strategy to reduce the lattice breathing of layered materials for enhanced sodium storage through interlayer spacing engineering. PMID- 26258425 TI - New circulating biomarkers for predicting cardiovascular death in healthy population. AB - There is interest to analyse newer biomarkers to identify healthy individuals at risk to develop cardiovascular disease (CVD) incidents and death. To determine in healthy individuals new circulating protein biomarkers, whose systemic levels may be associated with the risk of future development of CVD incidents and death. The study was performed in 82 individuals from the Malmo Diet and Cancer study cohort, free from CVD of whom 41 developed CVD and 41 did not. Plasma proteins related to inflammation and thrombo-coagulating processes were analysed. alpha1 antitrypsin isotype 3 plasma levels were significantly higher while apolipoprotein J plasma levels were lower in participants that developed CVD incidents than those that did not develop acute cardiovascular episode. Of 82 participants, 17 died by CVD causes. There were proteins whose expression in plasma was significantly higher in participants suffering CVD death as compared with those that did not die by CVD. These proteins included: fibrinogen beta chain isotypes 1 and 3, fibrinogen-gamma-chain isotype 2, vitamin D-binding protein isotypes 1, 2 and 3, alpha1-antitrypsin isotypes 3 and 6, haptoglobin isotypes 3,4,5 and 5, haemopexin isotypes 1 and 2, and Rho/Rac guanine nucleotide exchange factor 2. Moreover, apolipoprotein J plasma levels were found lower in participants that died by cardiovascular cause. Association between plasma levels of proteins and CVD death was independent of age, gender, conventional risk factors and plasma C-reactive protein levels. Several protein plasma levels and protein isotypes related to inflammation and thrombo-coagulating phenomena were independently associated with the risk of future CVD death. PMID- 26258430 TI - Real-Time Automatic Segmentation of Optical Coherence Tomography Volume Data of the Macular Region. AB - Optical coherence tomography (OCT) is a high speed, high resolution and non invasive imaging modality that enables the capturing of the 3D structure of the retina. The fast and automatic analysis of 3D volume OCT data is crucial taking into account the increased amount of patient-specific 3D imaging data. In this work, we have developed an automatic algorithm, OCTRIMA 3D (OCT Retinal IMage Analysis 3D), that could segment OCT volume data in the macular region fast and accurately. The proposed method is implemented using the shortest-path based graph search, which detects the retinal boundaries by searching the shortest-path between two end nodes using Dijkstra's algorithm. Additional techniques, such as inter-frame flattening, inter-frame search region refinement, masking and biasing were introduced to exploit the spatial dependency between adjacent frames for the reduction of the processing time. Our segmentation algorithm was evaluated by comparing with the manual labelings and three state of the art graph-based segmentation methods. The processing time for the whole OCT volume of 496*644*51 voxels (captured by Spectralis SD-OCT) was 26.15 seconds which is at least a 2-8 fold increase in speed compared to other, similar reference algorithms used in the comparisons. The average unsigned error was about 1 pixel (~ 4 microns), which was also lower compared to the reference algorithms. We believe that OCTRIMA 3D is a leap forward towards achieving reliable, real-time analysis of 3D OCT retinal data. PMID- 26258431 TI - Fast flow microfluidics and single-molecule fluorescence for the rapid characterization of alpha-synuclein oligomers. AB - alpha-Synuclein oligomers can be toxic to cells and may be responsible for cell death in Parkinson's disease. Their typically low abundance and highly heterogeneous nature, however, make such species challenging to study using traditional biochemical techniques. By combining fast-flow microfluidics with single-molecule fluorescence, we are able to rapidly follow the process by which oligomers of alphaS are formed and to characterize the species themselves. We have used the technique to show that populations of oligomers with different FRET efficiencies have varying stabilities when diluted into low ionic strength solutions. Interestingly, we have found that oligomers formed early in the aggregation pathway have electrostatic repulsions that are shielded in the high ionic strength buffer and therefore dissociate when diluted into lower ionic strength solutions. This property can be used to isolate different structural groups of alphaS oligomers and can help to rationalize some aspects of alphaS amyloid fibril formation. PMID- 26258432 TI - Ethylene Glycol Intercalated Cobalt/Nickel Layered Double Hydroxide Nanosheet Assemblies with Ultrahigh Specific Capacitance: Structural Design and Green Synthesis for Advanced Electrochemical Storage. AB - Because of the rapid depletion of fossil fuels and severe environmental pollution, more advanced energy-storage systems need to possess dramatically improved performance and be produced on a large scale with high efficiency while maintaining low-enough costs to ensure the higher and wider requirements. A facile, energy-saving process was successfully adopted for the synthesis of ethylene glycol intercalated cobalt/nickel layered double hydroxide (EG-Co/Ni LDH) nanosheet assembly variants with higher interlayer distance and tunable transitional-metal composition. At an optimized starting Co/Ni ratio of 1, the nanosheet assemblies display a three-dimensional, spongelike network, affording a high specific surface area with advantageous mesopore structure in 2-5 nm containing large numbers of about 1.2 nm micropores for promoting electrochemical reaction. An unprecedented electrochemical performance was achieved, with a specific capacitance of 4160 F g(-1) at a discharge current density of 1 A g(-1) and of 1313 F g(-1) even at 50 A g(-1), as well as excellent cycling ability. The design and optimization of EG-Co/Ni LDH nanosheets in compositions, structures, and performances, in conjunction with the easy and relatively "green" synthetic process, will play a pivotal role in meeting the needs of large-scale manufacture and widespread application for advanced electrochemical storage. PMID- 26258433 TI - Sialic Acid Glycoengineering Using an Unnatural Sialic Acid for the Detection of Sialoglycan Biosynthesis Defects and On-Cell Synthesis of Siglec Ligands. AB - Sialoglycans play a vital role in physiology, and aberrant sialoglycan expression is associated with a broad spectrum of diseases. Since biosynthesis of sialoglycans is only partially regulated at the genetic level, chemical tools are crucial to study their function. Here, we report the development of propargyloxycarbonyl sialic acid (Ac5NeuNPoc) as a powerful tool for sialic acid glycoengineering. Ac5NeuNPoc showed strongly increased labeling efficiency and exhibited less toxicity compared to those of widely used mannosamine analogues in vitro and was also more efficiently incorporated into sialoglycans in vivo. Unlike mannosamine analogues, Ac5NeuNPoc was exclusively utilized in the sialoglycan biosynthesis pathway, allowing a genetic defect in sialic acid biosynthesis to be specifically detected. Furthermore, Ac5NeuNPoc-based sialic acid glycoengineering enabled the on-cell synthesis of high-affinity Siglec-7 ligands and the identification of a novel Siglec-2 ligand. Thus, Ac5NeuNPoc glycoengineering is a highly efficient, nontoxic, and selective approach to study and modulate sialoglycan interactions on living cells. PMID- 26258434 TI - Toward an Understanding of the Ambiguous Electron Paramagnetic Resonance Spectra of the Iminoxy Radical from o-Fluorobenzaldehyde Oxime: Density Functional Theory and ab Initio Studies. AB - Iminoxy radicals (R1R2C?N-O*) possess an inherent ability to exist as E and Z isomers. Although isotropic hyperfine couplings for the species with R1 = H allow one to distinguish between E and Z, unequivocal assignment of the parameters observed in the EPR spectra of the radicals without the hydrogen atom at the azomethine carbon to the right isomer is not a simple task. The iminoxyl derived from o-fluoroacetophenone oxime (R1 = CH3 and R2 = o-FC6H5) appears to be a case in point. Moreover, for its two isomers the rotation of the o-FC6H5 group brings into existence the syn and anti conformers, depending on the mutual orientation of the F atom and C?N-O* group, making a description of hyperfine couplings to structure even more challenging. To accomplish this, a vast array of theoretical methods (DFT, OO-SCS-MP2, QCISD) was used to calculate the isotropic hyperfine couplings. The comparison between experimental and theoretical values revealed that the E isomer is the dominant radical form, for which a fast interconversion between anti and syn conformers is expected. In addition, the origin of the significant AF increase with solvent polarity was analyzed. PMID- 26258435 TI - Model Peptide Studies Reveal a Mixed Histidine-Methionine Cu(I) Binding Site at the N-Terminus of Human Copper Transporter 1. AB - Copper is a vital metal cofactor in enzymes that are essential to myriad biological processes. Cellular acquisition of copper is primarily accomplished through the Ctr family of plasma membrane copper transport proteins. Model peptide studies indicate that the human Ctr1 N-terminus binds to Cu(II) with high affinity through an amino terminal Cu(II), Ni(II) (ATCUN) binding site. Unlike typical ATCUN-type peptides, the Ctr1 peptide facilitates the ascorbate-dependent reduction of Cu(II) bound in its ATCUN site by virtue of an adjacent HH (bis-His) sequence in the peptide. It is likely that the Cu(I) coordination environment influences the redox behavior of Cu bound to this peptide; however, the identity and coordination geometry of the Cu(I) site has not been elucidated from previous work. Here, we show data from NMR, XAS, and structural modeling that sheds light on the identity of the Cu(I) binding site of a Ctr1 model peptide. The Cu(I) site includes the same bis-His site identified in previous work to facilitate ascorbate-dependent Cu(II) reduction. The data presented here are consistent with a rational mechanism by which Ctr1 provides coordination environments that facilitate Cu(II) reduction prior to Cu(I) transport. PMID- 26258436 TI - Molecular Switching via Multiplicity-Exclusive E/Z Photoisomerization Pathways. AB - Mutual exclusivity in the nature of forward and reserve isomerization pathways holds promise for predictably controlling responses of photoswitchable materials according to molecular structure or external stimuli. Herein we have characterized the E/Z photoisomerization mechanisms of the visible-light triggered switch 1,2-dithienyl-1,2-dicyanoethene (4TCE) in chlorobenzene with ultrafast transient absorption spectroscopy. We observe that switching mechanisms occur exclusively by relaxation through electronic manifolds of different spin multiplicity: trans-to-cis isomerization only occurs via electronic relaxation within the singlet manifold on a time scale of 40 ps; in contrast, cis-to-trans isomerization is not observed above 440 nm, but occurs via two rapid ISC processes into and out of the triplet manifold on time scales of ~2 ps and 0.4 ns, respectively, when excited at higher energies (e.g., 420 nm). Observation of ultrafast ISC in cis-4TCE is consistent with photoinduced dynamics of related thiophene-based oligomers. Interpretation of the photophysical pathways underlying these isomerization reactions is supported by the observation that cis to-trans isomerization occurs efficiently via triplet-sensitized energy transfer, whereas trans-to-cis isomerization does not. Quantum-chemical calculations reveal that the T1 potential energy surface is barrierless along the coordinate of the central ethylene dihedral angle (theta) from the cis Franck-Condon region (theta = 175 degrees ) to geometries that are within the region of the trans ground state well; furthermore, the T1 and S1 surfaces cross with a substantial spin orbital coupling. In total, we demonstrate that E/Z photoswitching of 4TCE operates by multiplicity-exclusive pathways, enabling additional means for tailoring switch performance by manipulating spin-orbit couplings through variations in molecular structure or physical environment. PMID- 26258437 TI - Structure-Activity and Structure-Property Relationship and Exploratory in Vivo Evaluation of the Nanomolar Keap1-Nrf2 Protein-Protein Interaction Inhibitor. AB - Directly disrupting the Keap1-Nrf2 protein-protein interaction (PPI) is an effective way to activate Nrf2. Using the potent Keap1-Nrf2 PPI inhibitor that was reported by our group, we conducted a preliminary investigation of the structure-activity and structure-property relationships of the ring systems to improve the drug-like properties. Compound 18e, which bore p-acetamido substituents on the side chain phenyl rings, was the best choice for balancing PPI inhibition activity, physicochemical properties, and cellular Nrf2 activity. Cell-based experiments with 18e showed that the Keap1-Nrf2 PPI inhibitor can activate Nrf2 and induce the expression of Nrf2 downstream proteins in an Nrf2 dependent manner. An exploratory in vivo experiment was carried out to further evaluate the anti-inflammatory effects of 18e in a LPS-challenged mouse model. The primary results indicated that 18e could reduce the level of circulating pro inflammatory cytokines induced by LPS and relieve the inflammatory response. PMID- 26258438 TI - Ship Compliance in Emission Control Areas: Technology Costs and Policy Instruments. AB - This paper explores whether a Panama Canal Authority pollution tax could be an effective economic instrument to achieve Emission Control Area (ECA)-like reductions in emissions from ships transiting the Panama Canal. This tariff-based policy action, whereby vessels in compliance with International Maritime Organisation (IMO) ECA standards pay a lower transit tariff than noncompliant vessels, could be a feasible alternative to petitioning for a Panamanian ECA through the IMO. A $4.06/container fuel tax could incentivize ECA-compliant emissions reductions for nearly two-thirds of Panama Canal container vessels, mainly through fuel switching; if the vessel(s) also operate in IMO-defined ECAs, exhaust-gas treatment technologies may be cost-effective. The RATES model presented here compares current abatement technologies based on hours of operation within an ECA, computing costs for a container vessel to comply with ECA standards in addition to computing the Canal tax that would reduce emissions in Panama. Retrofitted open-loop scrubbers are cost-effective only for vessels operating within an ECA for more than 4500 h annually. Fuel switching is the least-cost option to industry for vessels that operate mostly outside of ECA regions, whereas vessels operating entirely within an ECA region could reduce compliance cost with exhaust-gas treatment technology (scrubbers). PMID- 26258439 TI - Scalable Production of Si Nanoparticles Directly from Low Grade Sources for Lithium-Ion Battery Anode. AB - Silicon, one of the most promising candidates as lithium-ion battery anode, has attracted much attention due to its high theoretical capacity, abundant existence, and mature infrastructure. Recently, Si nanostructures-based lithium ion battery anode, with sophisticated structure designs and process development, has made significant progress. However, low cost and scalable processes to produce these Si nanostructures remained as a challenge, which limits the widespread applications. Herein, we demonstrate that Si nanoparticles with controlled size can be massively produced directly from low grade Si sources through a scalable high energy mechanical milling process. In addition, we systematically studied Si nanoparticles produced from two major low grade Si sources, metallurgical silicon (~99 wt % Si, $1/kg) and ferrosilicon (~83 wt % Si, $0.6/kg). It is found that nanoparticles produced from ferrosilicon sources contain FeSi2, which can serve as a buffer layer to alleviate the mechanical fractures of volume expansion, whereas nanoparticles from metallurgical Si sources have higher capacity and better kinetic properties because of higher purity and better electronic transport properties. Ferrosilicon nanoparticles and metallurgical Si nanoparticles demonstrate over 100 stable deep cycling after carbon coating with the reversible capacities of 1360 mAh g(-1) and 1205 mAh g( 1), respectively. Therefore, our approach provides a new strategy for cost effective, energy-efficient, large scale synthesis of functional Si electrode materials. PMID- 26258440 TI - Ferulic Acid-Based Polymers with Glycol Functionality as a Versatile Platform for Topical Applications. AB - Ferulic acid-based polymers with aliphatic linkages have been previously synthesized via solution polymerization methods, yet they feature relatively slow ferulic acid release rates (~11 months to 100% completion). To achieve a more rapid release rate as required in skin care formulations, ferulic acid-based polymers with ethylene glycol linkers were prepared to increase hydrophilicity and, in turn, increase ferulic acid release rates. The polymers were characterized using nuclear magnetic resonance and Fourier transform infrared spectroscopies to confirm chemical composition. The molecular weights, thermal properties (e.g., glass transition temperature), and contact angles were also obtained and the polymers compared. Polymer glass transition temperature was observed to decrease with increasing linker molecule length, whereas increasing oxygen content decreased polymer contact angle. The polymers' chemical structures and physical properties were shown to influence ferulic acid release rates and antioxidant activity. In all polymers, ferulic acid release was achieved with no bioactive decomposition. These polymers demonstrate the ability to strategically release ferulic acid at rates and concentrations relevant for topical applications such as skin care products. PMID- 26258441 TI - LCGserver: A Webserver for Exploring Evolutionary Trajectory of Gene Orders in a Large Number of Genomes. AB - Genes and chromosomes are highly organized; together with protein-coding sequence, gene structure at per gene level and gene order at cluster level are both variable in a context of lineages and under natural selection. How gene order and chromosome organization are related and selected remains to be illuminated. The number of newly-sequenced genomes from various taxa has been increasing rapidly, but there have not been easy-to-use web tools that allow better visualization for gene order in a large genome collection. Here, we describe a webserver, LCGserver (http://lcgbase.big.ac.cn/LCGserver/), for exploring evolutionary dynamics of gene orders over diverse lineages. This server provides gene order information at three levels: single gene, paired gene (a minimal cluster), and clustered gene (more than two genes). The most exclusive feature of LCGserver is alignment and visualization of neighboring genes based on orthology, allowing users to inspect all conserved and dynamic events of gene order along chromosomes in a lineage-specific manner. In addition, it categories paired genes into six patterns and identifies fully-conserved gene clusters within and among lineages. PMID- 26258442 TI - Feasibility of using glass-bead thermoluminescent dosimeters for radiotherapy treatment plan verification. AB - OBJECTIVE: To investigate the feasibility of using glass beads as novel thermoluminescent dosemeters (TLDs) for radiotherapy treatment plan verification. METHODS: Commercially available glass beads with a size of 1-mm thickness and 2 mm diameter were characterized as TLDs. Five clinical treatment plans including a conventional larynx, a conformal prostate, an intensity-modulated radiotherapy (IMRT) prostate and two stereotactic body radiation therapy (SBRT) lung plans were transferred onto a CT scan of a water-equivalent phantom (Solid Water((r)), Gammex, Middleton, WI) and the dose distribution recalculated. The number of monitor units was maintained from the clinical plan and delivered accordingly. The doses determined by the glass beads were compared with those measured by a graphite-walled ionization chamber, and the respective expected doses were determined by the treatment-planning system (TPS) calculation. RESULTS: The mean percentage difference between measured dose with the glass beads and TPS was found to be 0.3%, -0.1%, 0.4%, 1.8% and 1.7% for the conventional larynx, conformal prostate, IMRT prostate and each of the SBRT delivery techniques, respectively. The percentage difference between measured dose with the ionization chamber and glass bead was found to be -1.2%, -1.4%, -0.1%, -0.9% and 2.4% for the above-mentioned plans, respectively. The results of measured doses with the glass beads and ionization chamber in comparison with expected doses from the TPS were analysed using a two-sided paired t-test, and there was no significant difference at p < 0.05. CONCLUSION: It is feasible to use glass-bead TLDs as dosemeters in a range of clinical plan verifications. ADVANCES IN KNOWLEDGE: Commercial glass beads are utilized as low-cost novel TLDs for treatment-plan verification. PMID- 26258443 TI - From parent-child mutuality to security to socialization outcomes: developmental cascade toward positive adaptation in preadolescence. AB - A developmental cascade from positive early parent-child relationship to child security with the parent to adaptive socialization outcomes, proposed in attachment theory and often implicitly accepted but rarely formally tested, was examined in 100 mothers, fathers, and children followed from toddler age to preadolescence. Parent-child Mutually Responsive Orientation (MRO) was observed in lengthy interactions at 38, 52, 67, and 80 months; children reported their security with parents at age eight. Socialization outcomes (parent- and child reported cooperation with parental monitoring and teacher-reported school competence) were assessed at age 10. Mediation was tested with PROCESS. The parent-child history of MRO significantly predicted both mother-child and father child security. For mother-child dyads, security mediated links between history of MRO and cooperation with maternal monitoring and school competence, controlling for developmental continuity of the studied constructs. For father child dyads, the mediation effect was not evident. PMID- 26258444 TI - Merlin Isoforms 1 and 2 Both Act as Tumour Suppressors and Are Required for Optimal Sperm Maturation. AB - The tumour suppressor Merlin, encoded by the gene NF2, is frequently mutated in the autosomal dominant disorder neurofibromatosis type II, characterised primarily by the development of schwannoma and other glial cell tumours. However, NF2 is expressed in virtually all analysed human and rodent organs, and its deletion in mice causes early embryonic lethality. Additionally, NF2 encodes for two major isoforms of Merlin of unknown functionality. Specifically, the tumour suppressor potential of isoform 2 remains controversial. In this study, we used Nf2 isoform-specific knockout mouse models to analyse the function of each isoform during development and organ homeostasis. We found that both isoforms carry full tumour suppressor functionality and can completely compensate the loss of the other isoform during development and in most adult organs. Surprisingly, we discovered that spermatogenesis is strictly dependent on the presence of both isoforms. While the testis primarily expresses isoform 1, we noticed an enrichment of isoform 2 in spermatogonial stem cells. Deletion of either isoform was found to cause decreased sperm quality as observed by maturation defects and head/midpiece abnormalities. These defects led to impaired sperm functionality as assessed by decreased sperm capacitation. Thus, we describe spermatogenesis as a new Nf2-dependent process. Additionally, we provide for the first time in vivo evidence for equal tumour suppressor potentials of Merlin isoform 1 and isoform 2. PMID- 26258446 TI - Infections in Total Hip and Total Knee Arthroplasty: Development of a Score To Assess Endogenous Risk of Surgical Site Infections. AB - BACKGROUND: Surgical site infections (SSI) are a dreaded complication of total hip (THA) and knee arthroplasties (TKA), and are a major public health concern. Risk factors are well known, but no endogenous risk assessment score exists. The objective of this study to develop a score to assess endogenous risk of infection after THA or TKA. METHODS: All infections after TKA and THA implanted in the department of orthopedic surgery of a teaching hospital between January 2007 and December 2012 were included. Two control groups were matched to cases on the type of prosthesis (hip or knee; first-line or revision). RESULTS: Twenty-four SSIs after THA and 21 after TKA were registered (respective incidence during the study period: 1.56 and 1.91%). Relevant endogenous risk factors found were: Smoking (adjusted odds ratio=3.9), a BMI greater than 35 kg/mC (1.8), inflammatory rheumatism (7.3), and the number of operations (prosthetic or not) on the involved joint (2.9 per additional surgery). The average score of endogenous infection risk on all analyzed subjects was 3.37+/-3.33 (median=3, range=0-17). Mean scores were substantially different among cases and control groups: Respectively 5.84+/-4.04 vs 2.13+/-2.01 (p<0.0001). With a five-point threshold, the sensitivity and specificity of the score are respectively 62 and 91%. ASA score greater than or equal to three was not found to be substantial risk factor in this study (p=0.15). CONCLUSIONS: Endogenous infection risk score studied here was found to be relevant in discriminating cases from control groups, but requires validation in a larger cohort. PMID- 26258447 TI - Immediate effects of somatosensory stimulation on hand function in patients with poststroke hemiparesis: a randomized cross-over trial. AB - This study aimed to determine the immediate effects of somatosensory stimulation on hand function in patients with poststroke hemiparesis. Eleven patients with poststroke hemiparesis participated in this study. Four types (no stimulation, vibration, and light and rough touches) of somatosensory stimulation were performed randomly for 4 days applying only one type of somatosensory stimulation each day. The box and block test (BBT), the Jebsen-Taylor hand function test (JTHFT), hand grip strength (HGS), and movement distance and peak velocity of the wrist joint during a forward-reaching task were measured. The BBT and JTHFT scores for no stimulation [BBT: median (interquartile range), 0.00 (-1.00 to 1.00) and JTHFT: 2.57 (-0.47 to 4.92)] were significantly different from those for vibration [BBT: 3.00 (2.00-5.00) and JTHFT: -16.02 (-23.06 to -4.31)], light touch [BBT: 3.00 (1.00-4.00) and JTHFT: -5.00 (-21.20 to -0.94)], and rough touch [BBT: 2.00 (1.00-4.00) and JTHFT: -6.19 (-18.22 to -3.70)]. The JTHFT score was significantly higher for vibration than that for rough touch (P<0.05). The increase in HGS was significantly greater for light touch than that for no stimulation (P<0.05) and for vibration than that for light touch (P<0.05). There were significant differences for the sagittal and coronal planes in movement distance and for the sagittal and horizontal planes in peak velocity during the forward-reaching task (P<0.05). The findings suggest that somatosensory stimulation may be advantageous to improve the hand function of patients with poststroke hemiparesis, with more favorable effects observed in vibration stimulation. PMID- 26258448 TI - Predictors of self-efficacy in women on long-term sick leave. AB - Self-efficacy has been shown to be related to sick leave and to be a predictor of return to work after sickness absence. The aim of this study was to investigate whether factors related to sick leave predict self-efficacy in women on long-term sick leave because of pain and/or mental illness. This cross-sectional study uses baseline data from 337 Swedish women with pain and/or mental illness. All included women took part in vocational rehabilitation. Data were collected through a sick leave register and a baseline questionnaire. General self efficacy, sociodemographics, self-rated health, anxiety, depression, view of the future, and social support were measured and analyzed by univariate and multivariate linear regression analyses. The full multivariate linear regression model, which included mental health factors together with all measured factors, showed that anxiety and depression were the only predictive factors of lower self efficacy (adjusted R2=0.46, P<0.001) and explained 46% of the variance in self efficacy. The mean scores of general self-efficacy were low, especially in women born abroad, those with low motivation, those with uncertainties about returning to work, and women reporting distrust. Anxiety and depression are important factors to consider when targeting self-efficacy in vocational rehabilitation. PMID- 26258445 TI - Aptamers against pathogenic microorganisms. AB - An important current issue of modern molecular medicine and biotechnology is the search for new approaches to early diagnostic assays and adequate therapy of infectious diseases. One of the promising solutions to this problem might be a development of nucleic acid aptamers capable of interacting specifically with bacteria, protozoa, and viruses. Such aptamers can be used for the specific recognition of infectious agents as well as for blocking of their functions. The present review summarizes various modern SELEX techniques used in this field, and of several currently identified aptamers against viral particles and unicellular organisms, and their applications. The prospects of applying nucleic acid aptamers for the development of novel detection systems and antibacterial and antiviral drugs are discussed. PMID- 26258449 TI - Visual analog rating of mood by people with aphasia. AB - BACKGROUND: Considerable attention has been given to the identification of depression in stroke survivors with aphasia, but there is more limited information about other mood states. Visual analog scales are often used to collect subjective information from people with aphasia. However, the validity of these methods for communicating about mood has not been established in people with moderately to severely impaired language. OBJECTIVE: The dual purposes of this study were to characterize the relative endorsement of negative and positive mood states in people with chronic aphasia after stroke and to examine congruent validity for visual analog rating methods for people with a range of aphasia severity. METHODS: Twenty-three left-hemisphere stroke survivors with aphasia were asked to indicate their present mood by using two published visual analog rating methods. The congruence between the methods was estimated through correlation analysis, and scores for different moods were compared. RESULTS: Endorsement was significantly stronger for "happy" than for mood states with negative valence. At the same time, several participants displayed pronounced negative mood compared to previously published norms for neurologically healthy adults. Results from the two rating methods were moderately and positively correlated. CONCLUSIONS: Positive mood is prominent in people with aphasia who are in the chronic stage of recovery after stroke, but negative moods can also be salient and individual presentations are diverse. Visual analog rating methods are valid methods for discussing mood with people with aphasia; however, design optimization should be explored. PMID- 26258450 TI - Association between site of lesion and driving performance after ischemic stroke. AB - BACKGROUND: Stroke presents with heterogeneous recovery periods, severity, and manifestation of deficits, all of which may adversely impact fitness-to-drive. Little is known about the association between site of lesion and driving performance after stroke. OBJECTIVE: To investigate the association between site of stroke lesion and driving performance. METHOD: Seventy-three participants (age = 56 +/- 11 years; 66 men) underwent a detailed battery of visual, cognitive, and on-road tests to determine fitness-to-drive at about 10 months after ischemic stroke. Associations between stroke location and driving performance were calculated using rank biserial (r rb) correlation coefficients. Correlations were considered weak below 0.10, moderate between 0.10 and 0.49, and strong above 0.50. Wilcoxon rank sum tests were employed to discern differences in on-road driving performance between participants whose performance was of concern to the driving assessor and those who exhibited no major difficulties on the road. RESULTS: In all, 28 (38%) out of the 73 participants exhibited major difficulties on the road. Those who showed difficulties on the road performed worse in all driving skills (P < 0.05). Correlation analysis showed moderate to strong correlations between site of lesion and performance in several visual, cognitive and on-road tests. Lesions in the parietal lobe showed correlations ranging between 0.23 and 0.25 with driving skills including vehicle control and speed adaptations. Lesions in the occipital lobes correlated strongly with visual field (r rb = 0.53) and moderately with visual neglect (r rb = 0.28). CONCLUSIONS: Our results suggest that cortical lesions in the parietal and occipital lobes are associated with driving deficits after stroke. Further advances in our understanding of the neural correlates of driving performance may provide prognostic markers of fitness-to-drive and lead to early, targeted rehabilitation. PMID- 26258451 TI - Effects of the combination of respiratory muscle training and abdominal drawing in maneuver on respiratory muscle activity in patients with post-stroke hemiplegia: a pilot randomized controlled trial. AB - PURPOSE: No study has examined the effects of the combination of respiratory muscle training (RMT) and abdominal drawing-in maneuver (ADIM) on respiratory muscle activity and function in stroke patients during early pulmonary rehabilitation. The purpose of this study was to investigate the effects of RMT combined with ADIM on decreased respiratory muscle activity and function in patients with post-stroke hemiplegia. METHODS: Thirty-seven subjects with post stroke hemiplegia were randomly allocated to three groups; integrated training group (ITG), respiratory muscle training group (RMTG), and control group (CG). All of the subjects received routine therapy for stroke rehabilitation for 1 hour, five times a week for 6 weeks. Especially, the ITG received RMT using an incentive respiratory spirometer and ADIM using a Stabilizer, and the RMTG only received RMT using incentive respiratory spirometer for 15 minutes a day, five times a week for 6 weeks. Pulmonary function was evaluated using spirometry for measuring the forced vital capacity (FVC) and force expiratory volume in 1 second (FEV1). Additional surface electromyography (sEMG) analysis was included by measuring the respiratory muscle activity. RESULTS: Our results showed that changes between the pre- and post-test values of FVC (F = 12.50, P = 0.02) and FEV1 (F = 12.81, P = 0.01) (P < 0.05) in the ITG were significantly (P < 0.05) greater. Changes in EMG activation of the diaphragm (F = 13.75, P = 0.003) and external intercostal (F = 14.33, P = 0.002) (P < 0.01) muscles of patients in the ITG during maximal static inspiratory efforts were significantly (P < 0.05) greater than those in patients of the RMTG and the CG at post-test. CONCLUSIONS: Our findings suggested that RMT combined with ADIM could improve pulmonary function in patients with post-stroke hemiplegia. PMID- 26258452 TI - Joint position sense is bilaterally reduced for shoulder abduction and flexion in chronic hemiparetic individuals. AB - BACKGROUND: The stroke is the leading cause of adult disability in the world. One of the main complaints of individuals post-stroke refers to the loss of function of the upper limb, as evidenced during the performance of activities of daily living. This difficulty may be related to an important component of sensorimotor control, joint position sense, a submodality of proprioception. OBJECTIVES: To investigate whether the proprioception of both shoulders of chronic hemiparetic patients is altered during abduction and flexion. METHODS: Thirteen subjects with chronic hemiparesis due to ischemic stroke and 13 healthy subjects matched for gender and age was included. The joint sense position was assessed using a dynamometer. Absolute error for shoulder abduction and flexion at the 30 and 60 degrees was calculated. RESULTS: No difference was found between the paretic and non-paretic limbs in movements at both 30 and 60 degrees . Higher values of absolute error for both paretic and non-paretic limbs compared to the control were observed during abduction at 30 and at 60 degrees . CONCLUSIONS: Chronic ischemic post-stroke patients have bilateral proprioceptive deficits in the shoulder during abduction and flexion. But these deficits are dependent on the movement performed and the angle tested. The results demonstrate the need to include bilateral exercises and/or visual feedback in the rehabilitation program. PMID- 26258453 TI - Stair climbing test post-stroke: feasibility, convergent validity and metabolic, cardiac, and respiratory responses. AB - BACKGROUND: The 6-minute walk test (6MWT) and treadmill walk tests (TMW) are commonly used to assess post-stroke patients (PSP) aerobic capacity. However, these tests are not without their limitations (e.g. limited sensitivity to change and the use of external pacing). Therefore, there is a need for additional tools to assess PSP aerobic capacity. OBJECTIVE: To establish the feasibility, convergent validity, and metabolic, cardiac, and respiratory responses of a stair climbing test (SC), among chronic PSP. METHODS: Nineteen chronic PSP conducted SC, TMW, and 6 MWT. Metabolic (oxygen consumption - VO2), cardiac (heart rate), and respiratory (ventilation volume, breathing frequency, and tidal volume) measures were established. Adverse events were documented. Correlations established the convergent validity of the SC test. A repeated measures analysis of variance was performed to compare the participant's physiological responses at the end of the various tests. RESULTS: SC is feasible and safe, as all participants completed the test with no adverse events. The SC demonstrated convergent validity as numerous associations were found between SC and TMW, and 6 MWT. Metabolic, cardiac, and respiratory responses to the SC were significantly higher than these of the TMW and 6 MWT (e.g. VO2= 13.43 +/- 2.19, 11.01 +/- 2.0, and 11.26 +/- 1.87 ml/kg/min, respectively) (P < 0.05). CONCLUSIONS: SC is a feasible and valid test within chronic PSP. SC is more metabolically demanding than TMW and 6 MW and therefore, may enable appropriate endurance capacity measurement, especially for high functioning PSP. Negotiating stairs is a common community ambulation requirement. Therefore, it is appropriate to incorporate SC test in PSP testing battery. PMID- 26258454 TI - Classifying physical activity research following stroke using the behavioral epidemiologic framework. AB - BACKGROUND: Stroke is a significant public health issue in the USA and a need emerges to better understand how to reduce an individual's co-morbidity risk. Physical activity is one approach to improving the health of individuals and comprehensive literature supports increased activity as a means to reduce risk of morbidity and mortality. One approach to examining whether research in a field is addressing a public health issue is through application of the behavioral epidemiological framework. OBJECTIVE: To classify physical activity research for individuals following stroke into distinct phases so that efforts can be made to systematically address gaps and disseminate evidence-based practice. METHODS: Specific key words were identified and then searched through EBSCO host, PubMed, and Google Scholar. Physical activity and stroke literature from 2000-2014 was categorized into one of five discrete phases. Research in Phase 1 identified associations between activity and health; Phase 2 established valid measures of activity; Phase 3 examined determinants of behavior; Phase 4 evaluated activity interventions; and Phase 5 disseminated evidence-based practice. RESULTS: A comprehensive review of literature identified 202 articles with 70% categorized in Phase 1 (n = 141), 11% in Phase 2 (n = 23), 10% in Phase 3 (n = 20), 8% in Phase 4 (n = 15), and 1% in Phase 5 (n = 3). CONCLUSION: Findings suggest that physical activity research for individuals following stroke is in the early stages of development with less than 10% of research evaluating or disseminating interventions. PMID- 26258455 TI - Virtual rehabilitation via Nintendo Wii(r) and conventional physical therapy effectively treat post-stroke hemiparetic patients. AB - BACKGROUND: The Nintendo(r) Wii is a simple and affordable virtual therapy alternative. It may be used at home, and it is a motivating recreational activity that provides continuous feedback. However, studies comparing the use of the Nintendo(r) Wii to conventional physical therapy are needed. OBJECTIVE: To compare the effect of a rehabilitation treatment using the Nintendo(r) Wii (NW) with conventional physical therapy (CPT) to improve the sensorimotor function and quality of life for post-stroke hemiparetic patients. METHODS: The present study applied a randomized, blind, and controlled clinical trial. In total, 30 patients with post-stroke hemiparesis were evaluated. A total of 15 patients were randomly assigned to each group. The SF-36 quality of life and Fugl-Meyer scales were used to evaluate the patients. RESULTS: After treatment, the only variable that differed between the groups was the physical functioning domain of the SF-36 in the group that received conventional physical therapy. A significant difference was observed between both groups before and after treatment in terms of the following Fugl-Meyer scale items: passive movement and pain, motor function of the upper limbs (ULs), and balance. The CPT group also showed a significant difference with regard to their UL and lower limb (LL) coordination. The SF-36 scale analysis revealed a significant difference within both groups with regard to the following domains: physical functioning, role limitation due to physical aspects, vitality, and role limitation due to emotional aspects. The NW group also exhibited a significant difference in the mental health domain. The results indicate that both approaches improved the patients' performance in a similar manner. CONCLUSION: Virtual rehabilitation using the Nintendo Wii(r) and CPT both effectively treat post-stroke hemiparetic patients by improving passive movement and pain scores, motor function of the upper limb, balance, physical functioning, vitality, and the physical and emotional aspects of role functioning. PMID- 26258456 TI - Leap motion controlled videogame-based therapy for rehabilitation of elderly patients with subacute stroke: a feasibility pilot study. AB - BACKGROUND: The leap motion controller (LMC) is a new optoelectronic system for capturing motion of both hands and controlling a virtual environment. Differently from previous devices, it optoelectronically tracks the fine movements of fingers neither using glows nor markers. OBJECTIVE: This pilot study explored the feasibility of adapting the LMC, developed for videogames, to neurorehabilitation of elderly with subacute stroke. METHODS: Four elderly patients (71.50 +/- 4.51 years old) affected by stroke in subacute phase were enrolled and tested in a cross-over pilot trial in which six sessions of 30 minutes of LMC videogame-based therapy were added on conventional therapy. Measurements involved participation to the sessions, evaluated by means of the Pittsburgh Rehabilitation Participation Scale, hand ability and grasp force evaluated respectively by means of the Abilhand Scale and by means of the dynamometer. RESULTS: Neither adverse effects nor spasticity increments were observed during LMC training. Participation to the sessions was excellent in three patients and very good in one patient during the LMC trial. In this period, patients showed a significantly higher improvement in hand abilities (P = 0.028) and grasp force (P = 0.006). CONCLUSIONS: This feasibility pilot study was the first one using leap motion controller for conducting a videogame-based therapy. This study provided a proof of concept that LMC can be a suitable tool even for elderly patients with subacute stroke. LMC training was in fact performed with a high level of active participation, without adverse effects, and contributed to increase the recovery of hand abilities. PMID- 26258457 TI - Computer-Aided Identification of Anticonvulsant Effect of Natural Nonnutritive Sweeteners Stevioside and Rebaudioside A. AB - Steviol glycosides are natural constituents of Stevia rebaudiana (Bert.) Bert. (Asteraceae) that have recently gained worldwide approval as nonnutritive sweeteners by the Joint Food and Agriculture Organization/World Organization Expert Committee on Food Additives. Cheminformatic tools suggested that the aglycone steviol and several of its phase I metabolites were predicted as potential anticonvulsant agents effective in the seizure animal model maximal electroshock seizure (MES) test. Thus, aqueous infusion from S. rebaudiana was tested in the MES test (mice, intraperitoneal administration), confirming dose dependent anticonvulsant effect. Afterward, isolated stevioside and rebaudioside A were tested in the MES test, with positive results. Though drug repositioning most often focuses on known therapeutics, this article illustrates the possibilities of this strategy to find new functionalities and therapeutic indications for food constituents and natural products. PMID- 26258458 TI - Pigmented Dermatofibrosarcoma Protuberans and Blue Naevi with Similar Dermoscopy: A Case Report. PMID- 26258459 TI - Partial Amelioration of Medial Visceromotor Network Dysfunction in Major Depression by Sertraline. AB - OBJECTIVES: Major depression is associated with reduced cardiac vagal control, most commonly indexed by heart rate variability. To examine the dynamics of this abnormality, we examined within-participant covariation over time between brain activity, cardiac vagal control, and depressive symptoms in depressed patients treated with sertraline and in healthy volunteers. METHODS: Patients with depression and nondepressed control participants were enrolled in a 12-week protocol. After Week 0 assessment, patients began treatment with sertraline. Neural activity and vagal control were measured for all participants at Weeks 0, 2, 6, and 12 using functional magnetic resonance imaging and synchronized electrocardiographic recordings. At each of the four assessments, a moving window analysis was used to estimate vagal control as assessed by respiratory sinus arrhythmia (RSA) from the electrocardiographic data, which was then regressed onto functional magnetic resonance imaging activity. RESULTS: At baseline, patients showed reduced blood oxygen level-dependent RSA covariation compared with controls within multiple a priori brain regions associated with vagal control, collectively described as the medial visceromotor network (MVN). Sertraline treatment led to a significant increase in brain-RSA covariation for patients compared with controls, despite a lack of improvement in mean RSA. CONCLUSIONS: These data suggest a partial normalization of MVN dysfunction in depression during sertraline treatment. Specifically, results indicate a partial recovery of MVN function. However, this recovery was insufficient to cause a significant change in RSA levels. These results may help to explain both improvements with and limitations of sertraline treatment of depression. PMID- 26258461 TI - Integrating Telemental Healthcare with the Patient-Centered Medical Home Model. AB - OBJECTIVE: The purpose of this article is to discuss how telemental healthcare and the patient-centered medical home (PCMH) can be integrated to improve the quality of mental healthcare available. METHODS: This article outlines the components of a PCMH, and how the needs of this type of system of care can benefit from telemental healthcare. RESULTS: The princples of PCMHs are being increasingly promoted in a variety of settings. In order to fulfill these principles, mental heathcare must be a integral part of the care provided to patients within the PCMH. The mental healthcare workforce is inadequate to provide care for patients, particularly in rural and high-poverty areas. Telemental healthcare provides a means to extend mental health services to the PCMHs using a variety of models. CONCLUSIONS: Telemental healthcare offers unique opportunities to bridge the need for mental healthcare integration in the PCMH for all patients. PMID- 26258460 TI - Epidermal micrografts produced via an automated and minimally invasive tool form at the dermal/epidermal junction and contain proliferative cells that secrete wound healing growth factors. AB - OBJECTIVE: The aim of this scientific study was to assess epidermal micrografts for formation at the dermal-epidermal (DE) junction, cellular outgrowth, and growth factor secretion. Epidermal harvesting is an autologous option that removes only the superficial epidermal layer of the skin, considerably limiting donor site damage and scarring. Use of epidermal grafting in wound healing has been limited because of tedious, time-consuming, and inconsistent methodologies. Recently, a simplified, automated epidermal harvesting tool (CelluTome Epidermal Harvesting System; Kinetic Concepts Inc, San Antonio, Texas) that applies heat and suction concurrently to produce epidermal micrografts has become commercially available. The new technique of epidermal harvesting was shown to create viable micrografts with minimal patient discomfort and no donor-site scarring. DESIGN: This study was a prospective institutional review board-approved healthy human study. SETTING: This study was conducted at the multispecialty research facility, Clinical Trials of Texas, Inc, in San Antonio, Texas. PATIENTS: The participants were 15 healthy human volunteers. RESULTS: Epidermal micrografts formed at the DE junction, and migratory basal layer keratinocytes and melanocytes were proliferative in culture. Basement membrane-specific collagen type IV was also found to be present in the grafts, suggesting that the combination of heat and vacuum might cause partial delamination of the basement membrane. Viable basal cells actively secreted key growth factors important for modulating wound healing responses, including vascular endothelial growth factor, hepatocyte growth factor, granulocyte colony-stimulating factor, platelet-derived growth factor, and transforming growth factor alpha. CONCLUSIONS: Harvested epidermal micrografts retained their original keratinocyte structure, which is critical for potential re-epithelialization and repigmentation of a wound environment. PMID- 26258462 TI - Educational intervention to improve adherence to the Mediterranean diet among parents and their children aged 1-2 years. EniM clinical trial. AB - OBJECTIVE: The objective of the present study was to evaluate the effectiveness of an educational programme on healthy alimentation, carried out in day-care centres and aimed at the parents of children from 1 to 2 years of age, regarding the acquisition of healthy eating habits among themselves and their children. DESIGN: We performed a multicentre, multidisciplinary, randomized controlled study in a community setting. SETTING: The EniM study (nutritional intervention study among children from Mataro) was performed in twelve day-care centres in Mataro (Spain). Centres were randomized into a control group (CG) and an intervention group (IG). IG received four or five educational workshops on diet, CG did not have workshops. SUBJECTS: Children, not exclusively breast-fed, from 1 to 2 years of age, in the participating day-care centres and the persons responsible for their alimentation (mother or father). RESULTS: Thirty-five per cent of the IG did not attend the minimum of three workshops and were excluded. The CG included seventy-four children and seventy-two parents and the IG seventy five children and sixty-seven parents. Both groups were comparable at baseline. Basal adherence to the Mediterranean diet was 56.4 % in parents (Gerber index) and 7.7 points in children (Kidmed test). At 8 months, Mediterranean diet adherence had improved in the IG by 5.8 points in the Gerber index (P=0.01) and 0.6 points in the Kidmed test (P=0.02) compared with the CG. CONCLUSIONS: This educational intervention performed in parents at the key period of incorporation of a 1-2-year-old child to the family table showed significant increases in adherence of the parents to the Mediterranean diet, suggesting future improvement in different indicators of health and an expected influence on the diet of their children. PMID- 26258463 TI - Management of respiratory symptoms in paediatric palliative care. AB - PURPOSE OF REVIEW: Respiratory symptoms in children with life-limiting and life threatening conditions are common, distressing and have a lasting impact, yet there is a paucity of evidence to guide clinicians in their management. This article makes a series of recommendations for the management of the most frequent and distressing respiratory symptoms encountered in paediatrics (dyspnoea, cough, haemoptysis and retained secretions) with attention to the evidence from research. RECENT FINDINGS: There are very few paediatric studies exploring any aspect of respiratory symptoms in paediatric palliative care, so much of the evidence base has been drawn from adult studies, few of which have been published in the past 12-18 months. SUMMARY: In the absence of well designed paediatric studies we need to judiciously apply what we can extrapolate from adult studies to each child we are treating; selecting interventions and approaches carefully, adjusting them when there is no evidence of individual benefit. PMID- 26258464 TI - Progress in bladder cancer: is there light at the end of the tunnel? PMID- 26258466 TI - "Doing the Best We Can": Providing Care in a Malawian Antiretroviral Clinic. AB - Following a national policy shift toward universal access to antiretroviral therapy (ART) in Malawi, hospitals and clinics around the country made major changes to enable the provision of ART. In this already resource-limited environment, the provision of ART brought new health care delivery challenges to bear on both patients and health care professionals. The substance and form of these local interventions are affected by a multilayered global context. Drawing on fieldwork in an antiretroviral clinic in rural Malawi, this article discusses the daily implications of providing and receiving care in the context of a massive global shift in health policy, and argues that in order to fully understand the process of service rollout in all its complexity, care should be explored not only from the patients' perspective but also from that of local and international health care professionals and policymakers. PMID- 26258467 TI - The Human Dental Pulp Proteome and N-Terminome: Levering the Unexplored Potential of Semitryptic Peptides Enriched by TAILS to Identify Missing Proteins in the Human Proteome Project in Underexplored Tissues. AB - An underexplored yet widespread feature of the human proteome is the proteolytic proteoforms of proteins. We used terminal amine isotopic labeling of substrates (TAILS), a high-content N-terminal positional proteomics technique, for in-depth characterization of the human dental pulp proteome from its N-terminome and to provide data for the Chromosome-centric Human Proteome Project (C-HPP). Dental pulp is a unique connective tissue maintaining tooth sensation and structure by supporting a single cell layer of odontoblasts that synthesize mineralization competent dentine extracellular matrix. Therefore, we posited pulp to be a rich source of unique tissue-specific proteins and hence an abundant source of "missing" proteins as defined by neXtProt. From the identified 4332 proteins (false discovery rate (FDR) <= 0.7%), 21 528 unique peptides (FDR <= 1.0%) and 9079 unique N-termini, we analyzed N-terminal methionine excision, co- and posttranslational Nalpha-acetylation, protein maturation, and proteolytic processing. Apart from 227 candidate alternative translation initiation sites, most identified N-termini (78%) represented proteolytic processing and mechanism informative internal neo-N-termini, confirming a pervasive amount of proteolytic processing generated proteoforms in vivo. Furthermore, we identified 17 missing protein candidates for the C-HPP, highlighting the importance of using (i) less studied human specimens and (ii) orthogonal proteomic approaches such as TAILS to map the human proteome. The mass spectrometry raw data and metadata have been deposited to ProteomeXchange with the PXD identifier . PMID- 26258468 TI - Molecular Origin of DNA Kinking by Transcription Factors. AB - Binding of transcription factor (TF) proteins with DNA may cause severe kinks in the latter. Here, we investigate the molecular origin of the DNA kinks observed in the TF-DNA complexes using small molecule intercalation pathway, crystallographic analysis, and free energy calculations involving four different transcription factor (TF) protein-DNA complexes. We find that although protein binding may bend the DNA, bending alone is not sufficient to kink the DNA. We show that partial, not complete, intercalation is required to form the kink at a particular place in the DNA. It turns out that while amino acid alone can induce the desired kink through partial intercalation, protein provides thermodynamic stabilization of the kinked state in TF-DNA complexes. PMID- 26258469 TI - Ambient Temperature and Cerebrovascular Hemodynamics in the Elderly. AB - BACKGROUND AND PURPOSE: Some prior studies have linked ambient temperature with risk of cerebrovascular events. If causal, the pathophysiologic mechanisms underlying this putative association remain unknown. Temperature-related changes in cerebral vascular function may play a role, but this hypothesis has not been previously evaluated. METHODS: We evaluated the association between ambient temperature and cerebral vascular function among 432 participants >=65 years old from the MOBILIZE Boston Study with data on cerebrovascular blood flow, cerebrovascular resistance, and cerebrovascular reactivity in the middle cerebral artery. We used linear regression models to assess the association of mean ambient temperature in the previous 1 to 28 days with cerebrovascular hemodynamics adjusting for potential confounding factors. RESULTS: A 10 degrees C increase in the 21-day moving average of ambient temperature was associated with a 10.1% (95% confidence interval [CI], 2.2%, 17.3%) lower blood flow velocity, a 9.0% (95% CI, 0.7%, 18.0%) higher cerebrovascular resistance, and a 15.3% (95%CI, 2.7%, 26.4%) lower cerebral vasoreactivity. Further adjustment for ozone and fine particulate matter (PM2.5) did not materially alter the results. However, we found statistically significant interactions between ambient temperature and PM2.5 such that the association between temperature and blood flow velocity was attenuated at higher levels of PM2.5. CONCLUSIONS: In this elderly population, we found that ambient temperature was negatively associated with cerebral blood flow velocity and cerebrovascular vasoreactivity and positively associated with cerebrovascular resistance. Changes in vascular function may partly underlie the observed associations between ambient temperature and risk of cerebrovascular events. PMID- 26258470 TI - Biosynthesis of SUMOylated Proteins in Bacteria Using the Trypanosoma brucei Enzymatic System. AB - Post-translational modification with the Small Ubiquitin-like Modifier (SUMO) is conserved in eukaryotic organisms and plays important regulatory roles in proteins affecting diverse cellular processes. In Trypanosoma brucei, member of one of the earliest branches in eukaryotic evolution, SUMO is essential for normal cell cycle progression and is likely to be involved in the epigenetic control of genes crucial for parasite survival, such as those encoding the variant surface glycoproteins. Molecular pathways modulated by SUMO have started to be discovered by proteomic studies; however, characterization of functional consequences is limited to a reduced number of targets. Here we present a bacterial strain engineered to produce SUMOylated proteins, by transferring SUMO from T. brucei together with the enzymes essential for its activation and conjugation. Due to the lack of background in E. coli, this system is useful to express and identify SUMOylated proteins directly in cell lysates by immunoblotting, and SUMOylated targets can be eventually purified for biochemical or structural studies. We applied this strategy to describe the ability of TbSUMO to form chains in vitro and to detect SUMOylation of a model substrate, PCNA both from Saccharomyces cerevisiae and from T. brucei. To further validate targets, we applied an in vitro deconjugation assay using the T. brucei SUMO-specific protease capable to revert the pattern of modification. This system represents a valuable tool for target validation, mutant generation and functional studies of SUMOylated proteins in trypanosomatids. PMID- 26258471 TI - Distribution and Prevalence of Locoregional Recurrence after Video-Assisted Thoracoscopic Surgery for Primary Lung Cancer. AB - Background The aim of this study is to evaluate cases with locoregional recurrence after video-assisted thoracoscopic surgery (VATS) for primary lung cancer. Methods We reviewed 248 patients with primary lung cancer who underwent lobectomy or segmentectomy with mediastinal lymph node dissection by VATS between January 2005 and December 2011. Locoregional recurrence is defined as per its occurrence in (1) bronchial stump or lung parenchymal cut end, (2) ipsilateral pleura, and (3) ipsilateral hilar and mediastinal lymph nodes, and we analyzed recurrence rate and significant associated factors for locoregional recurrence by logistic regression analysis. Results There were 47 cases of postoperative recurrence, which consisted of 26 distant, 6 locoregional and distant, and 15 locoregional recurrences. The locoregional recurrence rate was 6.0%. Of the 15 locoregional recurrence cases, there were two cases of bronchial stump and lung parenchyma cut end (0.4%), five cases of ipsilateral pleura (2.0%), and eight cases of ipsilateral hilar and mediastinal lymph nodes (3.2%). Pleural and lymphovascular invasion and advanced stages were significant associated factors in univariate analysis. Multivariate analysis revealed that advanced stages were only a significant associated factor for locoregional recurrence (p < 0.01, odds ratio: 3.3). Conclusion Although locoregional recurrence rates of our surgical treatments for primary lung cancer by VATS might be acceptable, we should explore more effective modalities against pathologically proven local advanced lung cancer for preventing not only distant but also locoregional recurrences. PMID- 26258472 TI - Underlying Problems in Surgical Treatment of cT1-2N1 Non-Small Cell Lung Cancer. AB - Background Obtaining an accurate preoperative diagnosis of N1 in non-small cell lung cancer (NSCLC) is a major difficulty. The aim of this retrospective study was to evaluate the pathological and long-term outcomes of NSCLC patients clinically staged with N1 disease, to aid in the search for better treatment strategies. Materials and Methods We retrospectively reviewed the clinical records of 1,180 consecutive patients with NSCLC who underwent surgery for curative intent from 1991 to 2011 in our department. Data on 96 (8.1%) patients who had cT1-2N1 disease and underwent lobectomy or more extensive surgery were available. Results Only 32% of patients (n = 31) were confirmed to have pathological N1 disease, and 34 and 33% of patients were proven to have pN0 and pN2 disease, respectively. Female gender, <= 30 pack-year tobacco smoking history, adenocarcinoma, and left-sided disease were significantly associated with pathological upstaging (chi2 test). Multivariate analysis using logistic regression revealed left-sided disease to be independently associated with upstaging (relative risk 4.00, p = 0.015). Left-sided disease was more likely to be underestimated by clinical N staging than right-sided disease (chi2 test, p = 0.0001). Univariate and multivariate survival analyses demonstrated that left sided disease was an independent prognostic factor associated with poor outcomes (Cox proportional hazards regression: hazard ratio 2.27, p = 0.037). Conclusion The diagnostic accuracy of clinical N1 status was poor. Left-sided disease appeared to be understaged by the preoperative assessment of N status, and therefore, patients who might benefit from preoperative induction treatment would not receive it. PMID- 26258473 TI - Levels of daily light doses under changed day-night cycles regulate temporal segregation of photosynthesis and N2 Fixation in the cyanobacterium Trichodesmium erythraeum IMS101. AB - While the diazotrophic cyanobacterium Trichodesmium is known to display inverse diurnal performances of photosynthesis and N2 fixation, such a phenomenon has not been well documented under different day-night (L-D) cycles and different levels of light dose exposed to the cells. Here, we show differences in growth, N2 fixation and photosynthetic carbon fixation as well as photochemical performances of Trichodesmium IMS101 grown under 12L:12D, 8L:16D and 16L:8D L-D cycles at 70 MUmol photons m-2 s-1 PAR (LL) and 350 MUmol photons m-2 s-1 PAR (HL). The specific growth rate was the highest under LL and the lowest under HL under 16L:8D, and it increased under LL and decreased under HL with increased levels of daytime light doses exposed under the different light regimes, respectively. N2 fixation and photosynthetic carbon fixation were affected differentially by changes in the day-night regimes, with the former increasing directly under LL with increased daytime light doses and decreased under HL over growth-saturating light levels. Temporal segregation of N2 fixation from photosynthetic carbon fixation was evidenced under all day-night regimes, showing a time lag between the peak in N2 fixation and dip in carbon fixation. Elongation of light period led to higher N2 fixation rate under LL than under HL, while shortening the light exposure to 8 h delayed the N2 fixation peaking time (at the end of light period) and extended it to night period. Photosynthetic carbon fixation rates and transfer of light photons were always higher under HL than LL, regardless of the day-night cycles. Conclusively, diel performance of N2 fixation possesses functional plasticity, which was regulated by levels of light energy supplies either via changing light levels or length of light exposure. PMID- 26258475 TI - pGenN, a gene normalization tool for plant genes and proteins in scientific literature. AB - BACKGROUND: Automatically detecting gene/protein names in the literature and connecting them to databases records, also known as gene normalization, provides a means to structure the information buried in free-text literature. Gene normalization is critical for improving the coverage of annotation in the databases, and is an essential component of many text mining systems and database curation pipelines. METHODS: In this manuscript, we describe a gene normalization system specifically tailored for plant species, called pGenN (pivot-based Gene Normalization). The system consists of three steps: dictionary-based gene mention detection, species assignment, and intra species normalization. We have developed new heuristics to improve each of these phases. RESULTS: We evaluated the performance of pGenN on an in-house expertly annotated corpus consisting of 104 plant relevant abstracts. Our system achieved an F-value of 88.9% (Precision 90.9% and Recall 87.2%) on this corpus, outperforming state-of-art systems presented in BioCreative III. We have processed over 440,000 plant-related Medline abstracts using pGenN. The gene normalization results are stored in a local database for direct query from the pGenN web interface (proteininformationresource.org/pgenn/). The annotated literature corpus is also publicly available through the PIR text mining portal (proteininformationresource.org/iprolink/). PMID- 26258474 TI - A Non-Inferiority, Individually Randomized Trial of Intermittent Screening and Treatment versus Intermittent Preventive Treatment in the Control of Malaria in Pregnancy. AB - BACKGROUND: The efficacy of intermittent preventive treatment for malaria with sulfadoxine-pyrimethamine (IPTp-SP) in pregnancy is threatened in parts of Africa by the emergence and spread of resistance to SP. Intermittent screening with a rapid diagnostic test (RDT) and treatment of positive women (ISTp) is an alternative approach. METHODS AND FINDINGS: An open, individually randomized, non inferiority trial of IPTp-SP versus ISTp was conducted in 5,354 primi- or secundigravidae in four West African countries with a low prevalence of resistance to SP (The Gambia, Mali, Burkina Faso and Ghana). Women in the IPTp-SP group received SP on two or three occasions whilst women in the ISTp group were screened two or three times with a RDT and treated if positive for malaria with artemether-lumefantrine (AL). ISTp-AL was non-inferior to IPTp-SP in preventing low birth weight (LBW), anemia and placental malaria, the primary trial endpoints. The prevalence of LBW was 15.1% and 15.6% in the IPTp-SP and ISTp-AL groups respectively (OR = 1.03 [95% CI: 0.88, 1.22]). The mean hemoglobin concentration at the last clinic attendance before delivery was 10.97g/dL and 10.94g/dL in the IPTp-SP and ISTp-AL groups respectively (mean difference: -0.03 g/dL [95% CI: -0.13, +0.06]). Active malaria infection of the placenta was found in 24.5% and in 24.2% of women in the IPTp-SP and ISTp-AL groups respectively (OR = 0.95 [95% CI 0.81, 1.12]). More women in the ISTp-AL than in the IPTp-SP group presented with malaria parasitemia between routine antenatal clinics (310 vs 182 episodes, rate difference: 49.4 per 1,000 pregnancies [95% CI 30.5, 68.3], but the number of hospital admissions for malaria was similar in the two groups. CONCLUSIONS: Despite low levels of resistance to SP in the study areas, ISTp-AL performed as well as IPTp-SP. In the absence of an effective alternative medication to SP for IPTp, ISTp-AL is a potential alternative to IPTp in areas where SP resistance is high. It may also have a role in areas where malaria transmission is low and for the prevention of malaria in HIV positive women receiving cotrimoxazole prophylaxis in whom SP is contraindicated. TRIAL REGISTRATION: ClinicalTrials.gov NCT01084213 Pan African Clinical trials Registry PACT201202000272122. PMID- 26258477 TI - Antioxidant Properties of 2-Hydroxyethyl Methacrylate-Based Copolymers with Incorporated Sterically Hindered Amine. AB - A series of model linear copolymers of 2-hydroxyethyl methacrylate (HEMA) and a sterically hindered amine derivative [N-(2,2,6,6-tetramethyl-piperidin-4 yl)methacrylamide (HAS)] were synthesized and characterized. Scavenging activities of the copolymers against reactive oxygen species (peroxyl and hydroxyl radicals) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals were determined. It was found that copolymers with medium HAS content (3.5-4.0 mol %) were better scavengers than copolymers with lower and higher HAS content and also than polyHEMA and polyHAS homopolymers and the HAS monomer. Importantly, these copolymers compared favorably even to established low-molecular weight antioxidant standards (BHA and dexpanthenol). Monomer reactivity ratios were determined, and the microstructure of the copolymers was assessed. Subsequently, cross-linked copolymers in the powder and film forms with optimal HAS content were synthesized. Their scavenging activities against the three types of radicals were determined, revealing that these hydrogels are potent scavengers of reactive oxygen species. PMID- 26258476 TI - Correlations of salivary biomarkers with clinical assessments in patients with cystic fibrosis. AB - RATIONALE: Monitoring clinical disease status in cystic fibrosis frequently requires invasive collection of clinical samples. Due to its noninvasive collection process and direct anatomic relationship with the lower airway, saliva shows great potential as a biological fluid for cystic fibrosis monitoring. OBJECTIVES: To measure the levels of multiple protein markers in human saliva supernatants and investigate the possibility of utilizing them to provide a more quantitative measure of disease state for use in research and monitoring of patients with cystic fibrosis clinically. METHODS: Whole saliva samples were collected and processed from cystic fibrosis patients at two distinct time points (2010 and 2013) and measured by two separate platforms. In this cross sectional study, a convenience sample of 71 participants were recruited with samples measured by multiplexed fluorescence microarray (fiber microarray) and another 117 participant samples were measured by an automated, point-of-care, analyzer (SDReader) using a microsphere-based array via fluorescence sandwich immunoassay. For comparison, saliva from 56 and 50 healthy subjects were collected, respectively. The levels of six target proteins were quantified. Various demographic and clinical data, including spirometry, medical history, and clinicians' assessments were also collected from patients with cystic fibrosis on the day of saliva collection. MEASUREMENTS AND MAIN RESULTS: Similar trends were observed with both platforms and compared with healthy subjects, cystic fibrosis patients had significantly elevated levels of VEGF, IP-10, IL-8, and EGF as well as lower levels of MMP-9 (P <= 0.005) using fiber microarray and significantly elevated levels of IP-10, IL-8 with lower levels of MMP-9 and IL-1beta (P <= 0.02) using the SDReader. The levels of the six proteins correlated with each other significantly, and in some cases, biomarker levels could be used to differentiate between subgroups of patients with different clinical presentations. For example, IP-10 levels significantly correlated with FEV1 and disease severity (as evaluated by clinicians) with both platforms (P < 0.05). CONCLUSIONS: Significant variations of the levels of six proteins in saliva supernatants, and the correlations of these levels with clinical assessments, demonstrated the potential of saliva for cystic fibrosis research and monitoring. PMID- 26258478 TI - Water Splitting Processes on Mn4O4 and CaMn3O4 Model Cubane Systems. AB - Catalytic conversion of solar energy into chemical energy has been frequently investigated to develop clean energy sources in the last few decades. Metal oxide complexes show high potential for the catalytic conversion process, but the biochemical process in green plants has better efficiency than artificial photocatalysts consisting of metal oxides. In this work, the water splitting process is theoretically investigated using two synthetic model complexes whose structures are similar to the manganese-based oxygen evolving complex in photosystem II. Model A consists of four Mn atoms, and model B consists of three Mn atoms and a Ca atom in the core. Model A shows a better ability for water splitting than model B when comparing the highest reaction energy. The highest reaction energies are 2.56 and 2.99 eV for models A and B, respectively. In model B, the first oxidation in the water splitting process is exothermic, which is different from model A. In both models, the molecular oxygen generation step is endothermic by about 1.0-2.5 eV. PMID- 26258479 TI - Sequential substitution of K(+) bound to Na(+),K(+)-ATPase visualized by X-ray crystallography. AB - Na(+),K(+)-ATPase transfers three Na(+) from the cytoplasm into the extracellular medium and two K(+) in the opposite direction per ATP hydrolysed. The binding and release of Na(+) and K(+) are all thought to occur sequentially. Here we demonstrate by X-ray crystallography of the ATPase in E2.MgF4(2-).2K(+), a state analogous to E2.Pi.2K(+), combined with isotopic measurements, that the substitution of the two K(+) with congeners in the extracellular medium indeed occurs at different rates, substantially faster at site II. An analysis of thermal movements of protein atoms in the crystal shows that the M3-M4E helix pair opens and closes the ion pathway leading to the extracellular medium, allowing K(+) at site II to be substituted first. Taken together, these results indicate that site I K(+) is the first cation to bind to the empty cation-binding sites after releasing three Na(+). PMID- 26258480 TI - Elucidation of the structure of retroviral proteases: a reminiscence. AB - Determinations of only a very few protein structures had consequences comparable to the impact exerted by the structure of the protease encoded by HIV-1, published just over 25 years ago. The structure of this relatively small protein and its cousins from other retroviruses provided a clear target for a spectacularly successful structure-assisted drug design effort that offered new hope for controlling the then-escalating AIDS epidemic. This reminiscence is limited primarily to work conducted at the National Cancer Institute, and is not meant to be a comprehensive history of the field, but is rather an attempt to provide a very personal account of how the structures of this most thoroughly studied crystallographic target were determined. PMID- 26258481 TI - Targeted intracellular delivery of resveratrol to glioblastoma cells using apolipoprotein E-containing reconstituted HDL as a nanovehicle. AB - The objective of this study is to transport and deliver resveratrol to intracellular sites using apolipoprotein E3 (apoE3). Reconstituted high-density lipoprotein (rHDL) bearing resveratrol (rHDL/res) was prepared using phospholipids and the low-density lipoprotein receptor (LDLr)-binding domain of apoE3. Biophysical characterization revealed that resveratrol was partitioned into the phospholipid bilayer of discoidal rHDL/res particles (~19 nm diameter). Co-immunoprecipitation studies indicated that the LDLr-binding ability of apoE3 was retained. Cellular uptake of resveratrol to intracellular sites was evaluated in glioblastoma A-172 cells by direct fluorescence using chemically synthesized NBD-labeled resveratrol (res/NBD) embedded in rHDL/res. Competition and inhibition studies indicate that the uptake is by receptor mediated endocytosis via the LDLr, with co-localization of apoE3 and res/NBD in late endosomes/lysosomes. We propose that rHDL provides an ideal hydrophobic milieu to sequester resveratrol and that rHDL containing apoE3 serves as an effective "nanovehicle" to transport and deliver resveratrol to targeted intracellular sites. PMID- 26258482 TI - Resequencing Reveals Different Domestication Rate for BADH1 and BADH2 in Rice (Oryza sativa). AB - BADH1 and BADH2 are two homologous genes, encoding betaine aldehyde dehydrogenase in rice. In the present study, we scanned BADHs sequences of 295 rice cultivars, and 10 wild rice accessions to determine the polymorphisms, gene functions and domestication of these two genes. A total of 16 alleles for BADH1 and 10 alleles for BADH2 were detected in transcribed region of cultivars and wild species. Association study showed that BADH1 has significant correlation with salt tolerance in rice during germination stage, the SNP (T/A) in exon 4 is highly correlated with salt tolerance index (STI) (P<10(-4)). While, BADH2 was only responsible for rice fragrance, of which two BADH2 alleles (8 bp deletion in exon 7 and C/T SNP in exon 13) explain 97% of aroma variation in our germplasm. Theses indicate that there are no overlapping functions between the two homologous genes. In addition, a large LD block was detected in BADH2 region, however, there was no large LD blocks in a 4-Mb region of BADH1. We found that BADH2 region only showed significant bias in Tajima's D value from the balance. Extended haplotype homozygosity study revealed fragrant accessions had a large LD block that extended around the mutation site (8 bp deletion in exon 7) of BADH2, while both of the BADH1 alleles (T/A in exon 4) did not show large extended LD block. All these results suggested that BADH2 was domesticated during rice evolution, while BADH1 was not selected by human beings. PMID- 26258483 TI - New hosts for the mite Ornithonyssus bursa in Argentina. AB - The mite Ornithonyssus bursa (Berlese) (Mesostigmata: Macronyssidae) is considered a poultry pest causing important infestations in chickens and it is considered a potential vector of arbovirus. Despite being considered a common parasite in wild birds, there is scarce published information about its potential hosts and effects on them. Here we present new bird hosts for O. bursa, assess the presence of Alphavirus, Flavivirus and Bunyavirus in mites from three host species, and discuss its potential impact on wild bird populations. We found O. bursa infecting five raptor and six passerine wild bird species. For nine of these species, this is the first record of infection by O. bursa. Although all analysed mites were negative for the examined arboviruses, the small sample size of mites does not allow further conclusions at the present moment. Because of the general nature of this ectoparasite, its presence in migratory long dispersal and endangered bird species, and the seropositivity for arboviruses in some of the species studied here, we consider it critical to assess the role of O. bursa and other ectoparasites as vectors and reservoirs of pathogens and as potential deleterious agents in wild bird populations. PMID- 26258484 TI - The Gut Microbiota of Wild Mice. AB - The gut microbiota profoundly affects the biology of its host. The composition of the microbiota is dynamic and is affected by both host genetic and many environmental effects. The gut microbiota of laboratory mice has been studied extensively, which has uncovered many of the effects that the microbiota can have. This work has also shown that the environments of different research institutions can affect the mouse microbiota. There has been relatively limited study of the microbiota of wild mice, but this has shown that it typically differs from that of laboratory mice (and that maintaining wild caught mice in the laboratory can quite quickly alter the microbiota). There is also inter individual variation in the microbiota of wild mice, with this principally explained by geographical location. In this study we have characterised the gut (both the caecum and rectum) microbiota of wild caught Mus musculus domesticus at three UK sites and have investigated how the microbiota varies depending on host location and host characteristics. We find that the microbiota of these mice are generally consistent with those described from other wild mice. The rectal and caecal microbiotas of individual mice are generally more similar to each other, than they are to the microbiota of other individuals. We found significant differences in the diversity of the microbiotas among mice from different sample sites. There were significant correlations of microbiota diversity and body weight, a measure of age, body-mass index, serum concentration of leptin, and virus, nematode and mite infection. PMID- 26258485 TI - HIV-1 Dual Infected LTNP-EC Patients Developed an Unexpected Antibody Cross Neutralizing Activity. AB - This study evaluated the neutralization breadth in dually infected (DI) HIV-1 long-term non-progressor elite controller patients (LTNP-EC) using a representative minipanel of 6 viruses from 5 different subtypes. Our results showed an improved neutralization breadth in DI LTNP-EC patients when compared with matched LTNP single-infected patients. The role of viral diversity in neutralization was estimated with the Shannon Entropy and the p-distance in viral quasispecies. We found a positive correlation between neutralization breadth and diversity within the viral quasispecies. This correlation could explain why a group of LTNP-EC patients developed a broad neutralizing response despite having undetectable levels of viremia. PMID- 26258486 TI - Phencyclidine Disrupts the Auditory Steady State Response in Rats. AB - The Auditory Steady-State Response (ASSR) in the electroencephalogram (EEG) is usually reduced in schizophrenia (SZ), particularly to 40 Hz stimulation. The gamma frequency ASSR deficit has been attributed to N-methyl-D-aspartate receptor (NMDAR) hypofunction. We tested whether the NMDAR antagonist, phencyclidine (PCP), produced similar ASSR deficits in rats. EEG was recorded from awake rats via intracranial electrodes overlaying the auditory cortex and at the vertex of the skull. ASSRs to click trains were recorded at 10, 20, 30, 40, 50, and 55 Hz and measured by ASSR Mean Power (MP) and Phase Locking Factor (PLF). In Experiment 1, the effect of different subcutaneous doses of PCP (1.0, 2.5 and 4.0 mg/kg) on the ASSR in 12 rats was assessed. In Experiment 2, ASSRs were compared in PCP treated rats and control rats at baseline, after acute injection (5 mg/kg), following two weeks of subchronic, continuous administration (5 mg/kg/day), and one week after drug cessation. Acute administration of PCP increased PLF and MP at frequencies of stimulation below 50 Hz, and decreased responses at higher frequencies at the auditory cortex site. Acute administration had a less pronounced effect at the vertex site, with a reduction of either PLF or MP observed at frequencies above 20 Hz. Acute effects increased in magnitude with higher doses of PCP. Consistent effects were not observed after subchronic PCP administration. These data indicate that acute administration of PCP, a NMDAR antagonist, produces an increase in ASSR synchrony and power at low frequencies of stimulation and a reduction of high frequency (> 40 Hz) ASSR activity in rats. Subchronic, continuous administration of PCP, on the other hand, has little impact on ASSRs. Thus, while ASSRs are highly sensitive to NMDAR antagonists, their translational utility as a cross-species biomarker for NMDAR hypofunction in SZ and other disorders may be dependent on dose and schedule. PMID- 26258487 TI - Area-specific information processing in prefrontal cortex during a probabilistic inference task: a multivariate fMRI BOLD time series analysis. AB - INTRODUCTION: Discriminating spatiotemporal stages of information processing involved in complex cognitive processes remains a challenge for neuroscience. This is especially so in prefrontal cortex whose subregions, such as the dorsolateral prefrontal (DLPFC), anterior cingulate (ACC) and orbitofrontal (OFC) cortices are known to have differentiable roles in cognition. Yet it is much less clear how these subregions contribute to different cognitive processes required by a given task. To investigate this, we use functional MRI data recorded from a group of healthy adults during a "Jumping to Conclusions" probabilistic reasoning task. METHODS: We used a novel approach combining multivariate test statistics with bootstrap-based procedures to discriminate between different task stages reflected in the fMRI blood oxygenation level dependent signal pattern and to unravel differences in task-related information encoded by these regions. Furthermore, we implemented a new feature extraction algorithm that selects voxels from any set of brain regions that are jointly maximally predictive about specific task stages. RESULTS: Using both the multivariate statistics approach and the algorithm that searches for maximally informative voxels we show that during the Jumping to Conclusions task, the DLPFC and ACC contribute more to the decision making phase comprising the accumulation of evidence and probabilistic reasoning, while the OFC is more involved in choice evaluation and uncertainty feedback. Moreover, we show that in presumably non-task-related regions (temporal cortices) all information there was about task processing could be extracted from just one voxel (indicating the unspecific nature of that information), while for prefrontal areas a wider multivariate pattern of activity was maximally informative. CONCLUSIONS/SIGNIFICANCE: We present a new approach to reveal the different roles of brain regions during the processing of one task from multivariate activity patterns measured by fMRI. This method can be a valuable tool to assess how area-specific processing is altered in psychiatric disorders such as schizophrenia, and in healthy subjects carrying different genetic polymorphisms. PMID- 26258488 TI - Investigating Zigzag Film Growth Behaviors in Layer-by-Layer Self-Assembly of Small Molecules through a High-Gravity Technique. AB - The zigzag film growth behavior in the layer-by-layer (LbL) assembly method is a ubiquitous phenomenon for which the growth mechanism was rarely investigated, especially for small molecules. To interpret the zigzag increasing manner, we hypothesized that the desorption kinetics of small molecules was dominant for the film growth behavior and demonstrated this hypotheis by introducing the high gravity technique into the LbL assembly of a typical polyelectrolyte/small molecule system of polyethylenimine (PEI) and meso-tetra(4-carboxyphenyl)porphine (Por). The results showed that the high-gravity technique remarkably accelerated the desorption process of Por; the high-gravity LbL assembly provides a good platform to reveal the desorption kinetics of Por, which is tedious to study in conventional situation. We found that as much as 50 min is required for Por molecules to reach desorption equilibrium from the substrate to the bulk PEI solution for the conventional dipping method; however, the process could be accelerated and require only 100 s if a high-gravity field is used. Nonequilibrated desorption at 10 min for normal dipping and at 30 s for high gravity-field-assisted assembly both exhibited a zigzag film growth, but after reaching desorption equilibrium at 100 s under a high-gravity field, film growth began to cycle between assembly and complete disassembly instead of LbL assembly. For the first time we have proven that the high-gravity technique can also accelerate the desorption process and demonstrated the desorption-dependent mechanism of small molecules for zigzag film growth behaviors. PMID- 26258489 TI - Multigenerational Positive Family History of Psychiatric Disorders Is Associated With a Poor Prognosis in Bipolar Disorder. AB - The authors assessed how family history loading affected the course of illness in patients from the United States. A total of 676 outpatients with bipolar disorder from the United States rated their illness and provided a parental and grandparental history of mood disorder, substance abuse, and other clinical conditions. A positive family history for each illness was associated with almost all of the seven poor prognosis factors established in the study (abuse in childhood, early onset, anxiety and substance abuse comorbidity, rapid cycling, multiple episodes, and worsening of severity or frequency of episodes). Family history for psychiatric difficulties in parents and grandparents was associated with a more complex and difficult course of bipolar illness. PMID- 26258490 TI - Preinjury Emotional-Behavioral Functioning of Children With Lingering Problems After Mild Traumatic Brain Injury. AB - This study aimed to characterize preinjury emotional-behavioral functioning in pediatric patients with lingering problems after mild traumatic brain injury (TBI). The clinical case series design included 278 patients 8-17 years old. Parents retrospectively rated children's preinjury emotional-behavioral functioning on a broadband questionnaire. The rate of clinically significant preinjury anxiety was elevated compared with national norms. The number of previous TBIs was associated with clinically significant preinjury externalizing problems, suggesting a link between externalizing disorders and mild TBI exposure. Premorbid emotional-behavioral difficulties may play an important role in the establishment or maintenance of lingering symptoms after pediatric mild TBI. PMID- 26258491 TI - Research Trends in the Neuropsychiatry Literature Since the New Millennium. AB - The authors examined current research trends in neuropsychiatry by analyzing original research studies published since the new millennium. A total of 14,587 articles published between 2000 and 2013 were systematically screened from 10 neuropsychiatry journals, which were selected based on impact factor ranking. Clinical studies accounted for the highest proportion of neuropsychiatry research articles published since the new millennium (N=5,097; 68.9%), followed by laboratory studies (N=1,824; 24.7%) and service evaluation, classification, and historical studies (N=474; 6.4%). This study confirms that neuropsychiatry is a quintessentially clinical discipline with a continuing focus on phenomenological aspects, possibly reflecting the centrality of clinical observations to the diagnostic process. PMID- 26258492 TI - Pathological Laughter and Crying and Psychiatric Comorbidity After Traumatic Brain Injury. AB - There are limited data regarding the incidence of pathological laughter and crying (PLC) after traumatic brain injury (TBI). This study aimed to identify the occurrence of PLC in the first year after TBI and to determine whether there is a relationship between PLC and other clinical features or demographics. Subjects who sustained a first-time TBI were recruited from acute trauma units and were assessed at 3, 6, and 12 months after TBI. Rates of PLC at 3, 6, and 12 months after TBI were 21.4%, 17.5%, and 15.5%, respectively. Patients with PLC had higher percentages of psychiatric diagnoses, including personality changes, depressive disorders, and mood disorders secondary to a general medical condition, as well as higher rates of posttraumatic stress disorder. Univariate logistic and linear regression analyses indicated a significant association between PLC and scores on the Clinical Anxiety Scale 3 months after TBI and on the Hamilton Depression Rating Scale 12 months after TBI. Individuals who have PLC during the first year after TBI are more likely to have any psychiatric diagnosis as well as higher rates of mood and anxiety symptoms. In addition, PLC in the early TBI period may serve as a predictor of depression and anxiety symptoms at 12 months after TBI. PMID- 26258493 TI - Downregulation of GLS2 in glioblastoma cells is related to DNA hypermethylation but not to the p53 status. AB - Human phosphate-activated glutaminase (GA) is encoded by two genes: GLS and GLS2. Glioblastomas (GB) usually lack GLS2 transcripts, and their reintroduction inhibits GB growth. The GLS2 gene in peripheral tumors may be i) methylation- controlled and ii) a target of tumor suppressor p53 often mutated in gliomas. Here we assessed the relation of GLS2 downregulation in GB to its methylation and TP53 status. DNA demethylation with 5-aza-2'-deoxycytidine restored GLS2 mRNA and protein content in human GB cell lines with both mutated (T98G) and wild-type (U87MG) p53 and reduced the methylation of CpG1 (promoter region island), and CpG2 (first intron island) in both cell lines. In cell lines and clinical GB samples alike, methylated CpG islands were detected both in the GLS2 promoter (as reported earlier) and in the first intron of this gene. CpG methylation of either island was absent in GLS2-expressing non-tumoros brain tissues. Screening for mutation in the exons 5-8 of TP53 revealed a point mutation in only one out of seven GB examined. In conclusion, aberrant methylation of CpG islands, appear to contribute to silencing of GLS2 in GB by a mechanism bypassing TP53 mutations. (c) 2015 Wiley Periodicals, Inc. PMID- 26258494 TI - Shading Beats Binocular Disparity in Depth from Luminance Gradients: Evidence against a Maximum Likelihood Principle for Cue Combination. AB - Perceived depth is conveyed by multiple cues, including binocular disparity and luminance shading. Depth perception from luminance shading information depends on the perceptual assumption for the incident light, which has been shown to default to a diffuse illumination assumption. We focus on the case of sinusoidally corrugated surfaces to ask how shading and disparity cues combine defined by the joint luminance gradients and intrinsic disparity modulation that would occur in viewing the physical corrugation of a uniform surface under diffuse illumination. Such surfaces were simulated with a sinusoidal luminance modulation (0.26 or 1.8 cy/deg, contrast 20%-80%) modulated either in-phase or in opposite phase with a sinusoidal disparity of the same corrugation frequency, with disparity amplitudes ranging from 0'-20'. The observers' task was to adjust the binocular disparity of a comparison random-dot stereogram surface to match the perceived depth of the joint luminance/disparity-modulated corrugation target. Regardless of target spatial frequency, the perceived target depth increased with the luminance contrast and depended on luminance phase but was largely unaffected by the luminance disparity modulation. These results validate the idea that human observers can use the diffuse illumination assumption to perceive depth from luminance gradients alone without making an assumption of light direction. For depth judgments with combined cues, the observers gave much greater weighting to the luminance shading than to the disparity modulation of the targets. The results were not well-fit by a Bayesian cue-combination model weighted in proportion to the variance of the measurements for each cue in isolation. Instead, they suggest that the visual system uses disjunctive mechanisms to process these two types of information rather than combining them according to their likelihood ratios. PMID- 26258495 TI - The Darwinian tension: Romantic science and the causal laws of nature. AB - There have been attempts to subsume Charles Darwin's theory of evolution under either one of two distinct intellectual traditions: early Victorian natural science and its descendants in political economy (as exemplified by Herschel, Lyell, or Malthus) and the romantic approach to art and science emanating from Germany (as exemplified by Humboldt and Goethe). In this paper, it will be shown how these traditions may have jointly contributed to the design of Darwin's theory. The hypothesis is that their encounter created a particular tension in the conception of his theory which first opened up its characteristic field and mode of explanation. On the one hand, the domain of the explanandum was conceived of under a holistic and aesthetic view of nature that, in its combination with refined techniques of observation, was deeply indebted to Humboldt in particular. On the other hand, Darwin fashioned explanations for natural phenomena, so conceived, in order to identify their proper causes in a Herschelian spirit. The particular interaction between these two traditions in Darwin, it is concluded, paved the way for a transfer of the idea of causal laws to animate nature while salvaging the romantic idea of a complex, teleological and harmonious order of nature. PMID- 26258496 TI - Photodynamic Therapy for Actinic Keratoses: A Randomized Prospective Non sponsored Cost-effectiveness Study of Daylight-mediated Treatment Compared with Light-emitting Diode Treatment. AB - Daylight-mediated photodynamic therapy (DL-PDT) is considered as effective as conventional PDT using artificial light (light-emitting diode (LED)-PDT) for treatment of actinic keratoses (AK). This randomized prospective non-sponsored study assessed the cost-effectiveness of DL-PDT compared with LED-PDT. Seventy patients with 210 AKs were randomized to DL-PDT or LED-PDT groups. Effectiveness was assessed at 6 months. The costs included societal costs and private costs, including the time patients spent in treatment. Results are presented as incremental cost-effectiveness ratio (ICER). The total costs per patient were significantly lower for DL-PDT (?132) compared with LED-PDT (?170), giving a cost saving of ?38 (p = 0.022). The estimated probabilities for patients' complete response were 0.429 for DL-PDT and 0.686 for LED-PDT; a difference in probability of being healed of 0.257. ICER showed a monetary gain of ?147 per unit of effectiveness lost. DL-PDT is less costly and less effective than LED-PDT. In terms of cost-effectiveness analysis, DL-PDT provides lower value for money compared with LED-PDT. PMID- 26258497 TI - The influence of diabetic peripheral neuropathy on local postural muscle and central sensory feedback balance control. AB - Poor balance control and increased fall risk have been reported in people with diabetic peripheral neuropathy (DPN). Traditional body sway measures are unable to describe underlying postural control mechanism. In the current study, we used stabilogram diffusion analysis to examine the mechanism under which balance is altered in DPN patients under local-control (postural muscle control) and central control (postural control using sensory cueing). DPN patients and healthy age matched adults over 55 years performed two 15-second Romberg balance trials. Center of gravity sway was measured using a motion tracker system based on wearable inertial sensors, and used to derive body sway and local/central control balance parameters. Eighteen DPN patients (age = 65.4+/-7.6 years; BMI = 29.3+/ 5.3 kg/m2) and 18 age-matched healthy controls (age = 69.8+/-2.9; BMI = 27.0+/ 4.1 kg/m2) with no major mobility disorder were recruited. The rate of sway within local-control was significantly higher in the DPN group by 49% (healthy local-controlslope = 1.23+/-1.06*10-2 cm2/sec, P<0.01), which suggests a compromised local-control balance behavior in DPN patients. Unlike local-control, the rate of sway within central-control was 60% smaller in the DPN group (healthy central-controlslope-Log = 0.39+/-0.23, P<0.02), which suggests an adaptation mechanism to reduce the overall body sway in DPN patients. Interestingly, significant negative correlations were observed between central-control rate of sway with neuropathy severity (rPearson = 0.65-085, P<0.05) and the history of diabetes (rPearson = 0.58-071, P<0.05). Results suggest that in the lack of sensory feedback cueing, DPN participants were highly unstable compared to controls. However, as soon as they perceived the magnitude of sway using sensory feedback, they chose a high rigid postural control strategy, probably due to high concerns for fall, which may increase the energy cost during extended period of standing; the adaptation mechanism using sensory feedback depends on the level of neuropathy and the history of diabetes. PMID- 26258498 TI - Collective attention and stock prices: evidence from Google Trends data on Standard and Poor's 100. AB - Today's connected world allows people to gather information in shorter intervals than ever before, widely monitored by massive online data sources. As a dramatic economic event, recent financial crisis increased public interest for large companies considerably. In this paper, we exploit this change in information gathering behavior by utilizing Google query volumes as a "bad news" indicator for each corporation listed in the Standard and Poor's 100 index. Our results provide not only an investment strategy that gains particularly in times of financial turmoil and extensive losses by other market participants, but reveal new sectoral patterns between mass online behavior and (bearish) stock market movements. Based on collective attention shifts in search queries for individual companies, hence, these findings can help to identify early warning signs of financial systemic risk. However, our disaggregated data also illustrate the need for further efforts to understand the influence of collective attention shifts on financial behavior in times of regular market activities with less tremendous changes in search volumes. PMID- 26258499 TI - Progressive Ataxia and Palatal Tremor. PMID- 26258500 TI - Supramolecular Detoxification of Neurotoxic Nanofibrils of Small Molecules via Morphological Switch. AB - Insoluble amyloid plagues are likely cytoprotective, but the cellular mechanism remains less known. To model beta-amyloid we use a small peptide derivative to generate cytotoxic nanofibrils that cause the death of model neuron cells (i.e., PC12). The use of supramolecular interaction effectively converts the nanofibrils to nanoparticles that are innocuous to cells. This approach also removes the cytotoxicity of the fibrils to other mammalian cells (e.g., HeLa). Preliminary mechanistic study reveals that, in contrast to the fibrils, the particles promote the expression of TNFR2, a cell survival signal, and decrease the expression of TNFR1 and DR5, two extrinsic cell death receptors. As the first use of ligand receptor interaction to abrogate the cytotoxicity of nanoscale assemblies of small molecules, this work illustrates an effective way to use supramolecular interaction to control the morphology of supramolecular assemblies for modulating their biological activity. PMID- 26258501 TI - Characterization of the complete mitochondrial genome of the red crayfish, Procambarus clarkii (Decapoda: Cambaridae). AB - Here we present the complete mitochondrial (mt) genome of Procambarus clarkii (Decapoda: Cambaridae) and provide its annotation. The complete mt genome was determined to be 15 929 bp and contains 22 tRNA genes, 13 protein-coding genes (PCGs), two rRNA genes, and a D-loop region. The nucleotide composition was biased toward A + T nucleotides (72.91%) and the AT skew of this mt genome was slightly negative. All the 22 tRNA genes displayed a typical clover-leaf structure, with the exception of trnS1 (AGN). About 13 PCGs were initiated by ATN codons, except for cox1 and nad2 genes which were initiated by ACG and GTG, respectively. Six of the 13 PCGs harbor the incomplete termination codon by T or TA. The D-loop region of the mt genome was 1188 bp in length and the A + T content was 81.08%. Phylogenetic analysis showed that the placement of P. clarkii was within the Cambaridae. This mt genome sequence will provide a better understanding for crayfish evolution in the future. PMID- 26258502 TI - The sequence divergence in cytochrome C oxidase I gene of Culex quinquefasciatus mosquito and its comparison with four other Culex species. AB - The genetic diversity of Culex quinquefasciatus mosquito based on the standard barcode region of cytochrome C oxidase I (COI) gene fragment was studied in the present study. The COI gene sequences of Cx. quinquefasciatus were also compared with four other species of Genus Culex (i.e. Cx. tritaeniorhynchus, Cx. fuscocephala, Cx. pipiens, and Cx. theileri). Our data set included sequences of Culex mosquitoes from 16 different countries of world. The average intraspecific and interspecific divergences recorded were 0.67% and 8.27%, respectively. The clades for five species were clearly separated except Cx. quinquefasciatus and Cx. pipiens. It is concluded that the DNA barcoding is effective and reliable tool for the identification of selected Culex species but create little problem in case of sister species. PMID- 26258503 TI - The complete mitochondrial genome of the red-banded lobster Metanephrops thomsoni (Crustacea, Astacidea, Nephropidae): a novel gene order. AB - The complete mitochondrial genome (mitogenome) of the red-banded lobster, Metanephrops thomsoni (Decapoda, Astacidea, Nephropidae), is 19,835 bp in length and contains 13 protein-coding genes (PCGs), 2 ribosomal RNAs, 24 transfer RNAs (including additional copies of trnW and trnL1), and 2 control regions (CR). The mitogenome of M. thomsoni has 10 long intergenic sequences (71-237 bp) with a high AT content (70.0%). The two CRs show 59.6% similarity and have an identical sequence region with a length of 295 bp. The mitogenome of M. thomsoni shows a novel gene arrangement compared with the pancrustacean ground pattern and is identical to that of M. sibogae, except for the two additional tRNAs (trnW and trnL1). Phylogenetic tree from maximum likelihood analysis using the concatenated sequences of 13 PCGs depicted M. thomsoni as one of the members of the superfamily Nephropoidea within Astacidea. PMID- 26258504 TI - Characterization of the complete mitochondrial genome of Sickle pomfret Taractichthys steindachneri (Perciformes: Bramidae). AB - The complete mitogenome sequence of Taractichthys steindachneri was sequenced and analyzed in this study. The complete mitogenome of T. steindachneri is 16 723 bp in length, which contains 22 transfer RNAs, 2 ribosomal RNAs, 13 protein-coding genes and 2 non-coding region, a rep region and a control region (D-loop). This study will be useful for studying on the molecular systematic, taxonomic status and conservation genetics. PMID- 26258505 TI - The complete mitogenome of Jankowskia athleta (Lepidoptera: Geometridae). AB - We have sequenced the entire mitochondrial genome of Jankowskia athleta, that is 15 534 bp in length with a 79.53% A + T content (GenBank accession no. KR822683). The mt genome of J. athleta encodes 37 genes that are typically found in metazoan mt genomes, consists of 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes. Within the mt genome of J. athleta, there are six gene reading frame overlaps. The gene order is consistent with other yet sequenced mt genome in Geometridae. The mt genome of J. athleta has a 475 bp A + T-rich region with an A + T content of 93.47%. The result of phylogenetic analysis infers that J. athleta is more closely related to species of Geometridae than other moths. PMID- 26258506 TI - Complete mitochondrial genome and the phylogenetic position of the Blotchy swell shark Cephaloscyllium umbratile. AB - In this study, the complete mitochondrial genome of the Blotchy swell shark Cephaloscyllium umbratile was determined. It was a circle molecular (16 698 bp), contained 37 genes with typical order to that of most other vertebrates. The nucleotide composition was 31.0% A, 24.0% C, 14.0% G, and 31.3% T. There were 26 bp short intergenic spaces located in 11 gene junctions and 28 bp overlaps located in 7 gene junctions in the whole mitogenome. Two start codons (GTG and ATG) and two stop codons (TAG and TAA/T) were used in the protein-coding genes. The phylogenetic result showed that C. umbratile was clustered with Scyliorhinus canicula and formed the Scyliorhinidae clade, which was the most basal clade within Carcharhiniformes, and Carcharhinidae is not monophyletic. PMID- 26258507 TI - The complete mitochondrial genome of the Ephippus orbis (Perciformes: Ephippidae). AB - The complete mitochondrial genome of the Ephippus orbis has been sequenced. The mitochondrial genome is 16 670 bp in length, containing 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and one control region. The gene order and the composition of E. orbis mitochondrial genome were similar to that of most other vertebrates. The overall nucleotides base composition of the heavy strand is A (27.17%), G (16.41%), C (31.46%), and T (24.96%). With the exception of the NADH dehydrogenase subunit 6 (ND6) and eight tRNA genes, all other mitochondrial genes are encoded on the heavy strand. Seen from the phylogenetic tree ( Figure 1 ), E. orbis, Platax teira, and Platax orbicularis from the same family (Ephippidae) clustered into one branch and were significantly divergent from the other families of closely related fish species. PMID- 26258508 TI - Complete mitochondrial genome of a red calcified alga Calliarthron tuberculosum (Corallinales). AB - 454 GS FLX Titanium sequencing data were used to obtain the complete mitochondrial genome of Calliarthron tuberculosum (26,469 bp). The mitogenome contains 44 genes, including 2 ribosomal RNA, 19 transfer RNA, 5 ribosomal proteins, 1 ymf, 2 open reading frames (ORFs) and 16 genes involved in cellular respiration. The secY and rps12 are overlapped by 69 bp. rps3 and rpl16 also have a 45 bp overlapped region. Except for open reading frames near stem-loop region, the results show Calliarthron tuberculosum mtDNA has a high similarity with other Florideophyceae algae mitogenomes in gene synteny, structure and gene content. Phylogeny analysis indicates a close genetic relationship of Calliarthron tuberculosum with Sporolithon durum. PMID- 26258509 TI - Complete mitochondrial genome of the Taractes rubescens (Perciformes: Bramidae). AB - Taractes rubescens is a high vulnerable species which widely distributes in tropical and subtropical water in Pacific and Atlantic Ocean. The complete mitogenome sequence of T. rubescens was determined in this study. The complete mitogenome of T. rubescensis 16 720 bp in length, which contains 13 protein coding genes, 22 transfer RNAs, 2 ribosomal RNAs and a control region (D-loop). Furthermore, base composition of A, C, G and T is estimated to be 27.6%, 30.9%, 15.8% and 25.7%, respectively. The complete mtDNA sequence of T. rubescens provides a useful data for studying on the molecular systematic, stock assessment and conservation genetics. PMID- 26258510 TI - The complete mitochondrial genome of Sika deer Cervus nippon hortulorum (Artiodactyla: Cervidae) and phylogenetic studies. AB - Sika deer (Cervus nippon Temminck 1836) are classified in the order Artiodactyla, family Cervidae, subfamily Cervinae. At present, the phylogenetic studies of C. nippon are problematic. In this study, we first determined and described the complete mitochondrial sequence of the wild C. nippon hortulorum. The complete mitogenome sequence is 16 566 bp in length, including 13 protein-coding genes, two rRNA genes, 22 tRNA genes, a putative control region (CR) and a light-strand replication origin (OL). The overall base composition was 33.4% A, 28.6% T, 24.5% C, 13.5% G, with a 62.0% AT bias. The 13 protein-coding genes encode 3782 amino acids in total. To further validate the new determined sequences and phylogeny of Sika deer, phylogenetic trees involving 15 most closely related species available in GenBank database were constructed. These results are expected to provide useful molecular data for deer species identification and further phylogenetic studies of Artiodactyla. PMID- 26258511 TI - Complete mitochondrial genome of Lasiopodomys mandarinus mandarinus (Arvicolinae, Rodentia). AB - Mandarin voles (Lasiopodomys mandarinus) is a subterranean rodent species that are often used as a model for studying subterranean hypoxic stress in mammals. Its subspecies L. m. mandarinus span in cropland in most area of north China and is regarded as an agricultural pest. In this paper, the complete mitochondrial genome of L. m. mandarinus has been determined. Our results showed that the mitochondrial genome of L. m. mandarinus is a circular molecule of 16,367 bp, which contents 13 protein-coding, 22 tRNAs and 2 rRNAs genes. The overall base composition of the heavy strand is 32.47% A, 27.04% T, 27.01% C, and 13.47% G. with an AT content of 59.51%. PMID- 26258512 TI - Whole mitochondrial genome analysis in two families with dilated mitochondrial cardiomyopathy: detection of mutations in MT-ND2 and MT-TL1 genes. AB - Pathogenic mitochondrial DNA (mtDNA) mutations leading to mitochondrial dysfunction can cause cardiomyopathy and heart failure. These mutations were described in the mt-tRNA genes and in the mitochondrial protein-coding genes. The aim of this study was to identify the genetic defect in two patients belonging to two families with cardiac dysfunction associated to a wide spectrum of clinical phenotypes. The sequencing analysis of the whole mitochondrial DNA in the two patients and their parents revealed the presence of known polymorphisms associated to cardiomyopathy and two pathogenic mutations in DNA extracted from blood leucocytes: the heteroplasmic m.3243A > G mutation in the MT-TL1 gene in patient A; and the homoplasmic m.5182C > T mutation in the ND2 gene in patient B. Secondary structure analysis of the ND2 protein further supported the deleterious role of the m.5182C > T mutation, as it was found to be involved an extended imbalance in its hydrophobicity and affect its function. In addition, the mitochondrial variants identified in patients A and B classify both of them in the same haplogroup H2a2a1. PMID- 26258513 TI - Characteristics and phylogenetic studies of complete mitochondrial DNA based on the ricefield eel (Monopterus albus) from four different areas. AB - In this study, we cloned and sequenced the complete mitochondrial DNA of ricefield eel populations from four different areas (Guizhou province, Guangxi province, Hunan province, and Guangdong province) in China. The mitochondrial genome was 16,622 bp in length and deposited in the GenBank with accession numbers KP779622-KP779625. The organizations of the complete mitogenomes of the four ricefield eel were similar to those of other teleost species which contained 13 protein-coding genes, two rRNA genes, and 22 tRNA genes, as well as a putative control region (CR). Most of these genes were encoded on the H-strand, except for the ND6 and eight tRNA genes, all other genes were encoded on the H-strand. Phylogenetic analyses using N-J computational algorithms showed that the ricefield eel was clustered with Mastacembelus armatus (KJ184553) and they belong to Synbranchiformes. The four ricefield eel populations could be divided into two groups: Guangxi province and the other population cluster together. PMID- 26258514 TI - The complete chloroplast genome sequence of Alocasia macrorrhizos. AB - The complete chloroplast sequence of Alocasia macrorrhizos is 154 995 bp in length, containing a pair of inverted repeats of 25 944 bp separated by a large single-copy (LSC) region and a small single-copy (SSC) region of 87 366 bp and 15 741 bp, respectively. The chloroplast genome encodes 132 predicted functional genes, including 87 protein-coding genes, four ribosomal RNA genes, and 37 transfer RNA genes, 18 of which are duplicated in the inverted repeat regions. In these genes, 16 genes contained single intron and two genes comprising double introns. A maximum-likelihood phylogenetic analysis using complete chloroplast genome revealed that A. macrorrhizos does not belong to Araceae family, which infers that the A. macrorrhizos is distant from the species in Araceae family. PMID- 26258515 TI - Complete mitochondrial genome of Manchurian Zokor (Myospalax psilurus). AB - Manchurian Zokor (Myospalax psilurus) is a common subterranean rodents which have a wide distribution in Transbaikalia, east Mongolia, east and central China, and Far East of Russian. The complete mitochondrial (MT) genome of M. psilurus has been determined in this study. It is a 16,360 bp circular molecule containing 13 protein-coding, 22 tRNAs and 2 rRNAs genes. Except for the seven tRNA and Nd6 genes, all other mitogenes are encoded on the heavy strand. The overall nucleotide composition of the H-strand is 33.68% A, 28.77% T, 25.35% C, and 12.17% G. Total A + T content is 54.12%. PMID- 26258516 TI - Complete mitochondrial genome of Rhodeus ocellatus (Cypriniformes: Cyprinidae). AB - The complete mitogenome sequence of Rhodeus ocellatus (Kner) was determined using the next-generation sequencing (NGS). The genome was 16 761 bp in length and contained 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes and a control region. The overall nucleotide composition was 30.43% A, 27.50% T, 25.94% C, and 16.13% G, with an A + T bias of 57.93%. The gene composition and the arrangement of the R. ocellatus mitochondrial genome were similar to that of most other vertebrates. The complete mitochondrial genome sequence will help to study the evolutionary relationships and population genetics of Rhodeus fish. PMID- 26258517 TI - The complete mitochondrial genome of stretch spider Tetragnatha maxillosa (Araneae: Tetragnathidae). AB - The stretch spider Tetragnatha maxillosa (Araneae: Tetragnathidae) is found all over the world. In the present study, we investigated the complete mitochondrial genome of T. maxillosa and the mitogenome is a circular molecule of 14 414 bp in length, consists of 13 protein-coding genes, two ribosomal RNAs, 22 transfer RNAs, and a control region. The A + T content of the overall base composition of H-strand is 74.5% (T: 40.4%; C: 9.6%; A: 34.1%; G: 15.9%). COI gene begins with TTT as start codon, COII and COIII genes begin with TTG as start codon, ATP8, Cyt b, ND2, and ND4L genes begin with ATT as start codon, and other six protein coding genes start with ATA. ATP6, ATP8, COI, COIII, ND1, ND3, and ND6 genes are terminated with TAA as stop codon, Cyt b, ND2, ND4, ND4L, and ND5 end with T, and COII ends with TAG. In addition, the phylogenetic relationships from neighbor joining analyses based on the 13 concatenated PCGs indicated (Tetragnatha (Nephila (Argiope (Araneus, Neoscona)))). PMID- 26258518 TI - Complete mitochondrial genome of the Nemipterus virgatus (Perciformes: Nemipteridae). AB - The complete mitochondrial genome of the Nemipterus virgatus has been sequenced. The mitochondrial genome is 16 992 bp in length, containing 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and one control region. The gene order and composition of N. virgatus mitochondrial genome was similar to that of most other vertebrates. The overall nucleotides base composition of the light strand is A (27.89%), G (26.61%), C (16.45%), T (29.05%). With the exception of the NADH dehydrogenase subunit 6 (ND6) and eight tRNA genes, all other mitochondrial genes are encoded on the heavy strand. The tRNA-Ser2 gene lacked DHC arm and could not fold into a typical clover-leaf secondary structure. Seen from the phylogenetic tree, N. virgatus, Nemipterus japonicus, and Nemipterus bathybius from the same genus clustered into one branch. PMID- 26258519 TI - The complete mitochondrial genome of Sinibotia robusta (Cypriniformes: Cobitidae). AB - The Sinibotia robusta mitochondrial genome (GenBank accession no. KP979711) was a circular molecule of 16 575 bp in length, with two rRNA genes, 13 protein-coding genes, 22 tRNA genes, an l-strand replication origin (OL), and a control region (D-loop). The nucleotide acid composition of the entire mitogenome was 31.91% for A, 26.90% for C, 15.56% for G, and 25.63% for T, with an A + T content of 57.54%. And the A + T content of 12S rRNA, 16S rRNA, and D-loop was 51.26%, 56.17%, and 67.73%, respectively. PMID- 26258520 TI - Genetic basis of human left-right asymmetry disorders. AB - Humans and other vertebrates exhibit left-right (LR) asymmetric arrangement of the internal organs, and failure to establish normal LR asymmetry leads to internal laterality disorders, including situs inversus and heterotaxy. Situs inversus is complete mirror-imaged arrangement of the internal organs along LR axis, whereas heterotaxy is abnormal arrangement of the internal thoraco abdominal organs across LR axis of the body, most of which are associated with complex cardiovascular malformations. Both disorders are genetically heterogeneous with reduced penetrance, presumably because of monogenic, polygenic or multifactorial causes. Research in genetics of LR asymmetry disorders has been extremely prolific over the past 17 years, and a series of loci and disease genes involved in situs inversus and heterotaxy have been described. The review highlights the classification, chromosomal abnormalities, pathogenic genes and the possible mechanism of human LR asymmetry disorders. PMID- 26258522 TI - A novel utility function for energy-efficient power control game in cognitive radio networks. AB - Spectrum scarcity is a major challenge in wireless communications systems requiring efficient usage and utilization. Cognitive radio network (CRN) is found as a promising technique to solve this problem of spectrum scarcity. It allows licensed and unlicensed users to share the same licensed spectrum band. Interference resulting from cognitive radios (CRs) has undesirable effects on quality of service (QoS) of both licensed and unlicensed systems where it causes degradation in received signal-to-noise ratio (SIR) of users. Power control is one of the most important techniques that can be used to mitigate interference and guarantee QoS in both systems. In this paper, we develop a new approach of a distributed power control for CRN based on utility and pricing. QoS of CR user is presented as a utility function via pricing and a distributed power control as a non-cooperative game in which users maximize their net utility (utility-price). We define the price as a real function of transmit power to increase pricing charge of the farthest CR users. We prove that the power control game proposed in this study has Nash Equilibrium as well as it is unique. The obtained results show that the proposed power control algorithm based on a new utility function has a significant reduction in transmit power consumption and high improvement in speed of convergence. PMID- 26258521 TI - Development of Selective Covalent Janus Kinase 3 Inhibitors. AB - The Janus kinases (JAKs) and their downstream effectors, signal transducer and activator of transcription proteins (STATs), form a critical immune cell signaling circuit, which is of fundamental importance in innate immunity, inflammation, and hematopoiesis, and dysregulation is frequently observed in immune disease and cancer. The high degree of structural conservation of the JAK ATP binding pockets has posed a considerable challenge to medicinal chemists seeking to develop highly selective inhibitors as pharmacological probes and as clinical drugs. Here we report the discovery and optimization of 2,4-substituted pyrimidines as covalent JAK3 inhibitors that exploit a unique cysteine (Cys909) residue in JAK3. Investigation of structure-activity relationship (SAR) utilizing biochemical and transformed Ba/F3 cellular assays resulted in identification of potent and selective inhibitors such as compounds 9 and 45. A 2.9 A cocrystal structure of JAK3 in complex with 9 confirms the covalent interaction. Compound 9 exhibited decent pharmacokinetic properties and is suitable for use in vivo. These inhibitors provide a set of useful tools to pharmacologically interrogate JAK3-dependent biology. PMID- 26258523 TI - NMR and MD Studies Reveal That the Isolated Dengue NS3 Protease Is an Intrinsically Disordered Chymotrypsin Fold Which Absolutely Requests NS2B for Correct Folding and Functional Dynamics. AB - Dengue genome encodes a two component protease complex (NS2B-NS3pro) essential for the viral maturation/infectivity, thus representing a key drug target. Previously, due to its "complete insolubility", the isolated NS3pro could not be experimentally studied and it remains elusive what structure it adopts without NS2B and why NS2B is indispensable. Here as facilitated by our previous discovery, the isolated NS3pro has been surprisingly deciphered by NMR to be the first intrinsically-disordered chymotrypsin-like fold, which exists in a loosely packed state with non-native long-range interactions as revealed by paramagnetic relaxation enhancement (PRE). The disordered NS3pro appears to be needed for binding a human host factor to trigger the membrane remodeling. Moreover, we have in vitro refolded the NS3pro in complex with either NS2B (48-100) or the full length NS2B (1-130) anchored into the LMPC micelle, and the two complexes have similar activities but different dynamics. We also performed molecular dynamics (MD) simulations and the results revealed that NS2B shows the highest structural fluctuations in the complex, thus providing the dynamic basis for the observation on its conformational exchange between open and closed states. Remarkably, the NS2B cofactor plays a central role in maintaining the correlated motion network required for the catalysis as we previously decoded for the SARS 3CL protease. Indeed, a truncated NS2B (48-100;Delta77-84) with the flexible loop deleted is able to trap the NS2B-NS3pro complex in a highly dynamic and catalytically impotent state. Taken together, our study implies potential strategies to perturb the NS2B-NS3pro interface for design of inhibitors for treating dengue infection. PMID- 26258524 TI - Dose-responsive gene expression in suberoylanilide hydroxamic acid-treated resting CD4+ T cells. AB - DESIGN: Persistent latently infected CD4 T cells represent a major obstacle to HIV eradication. Histone deacetylase inhibitors (HDACis) are a proposed activation therapy. However, off-target effects on gene expression in host immune cells are poorly understood. We hypothesized that HDACi-modulated genes would be best identified with a dose-response analysis. METHODS: Resting primary CD4 T cells were treated with 0.34, 1, 3, or 10 MUmol/l of the HDACi, suberoylanilide hydroxamic acid (SAHA), for 24 h and subjected to microarray gene expression analysis. Genes with dose-correlated expression were filtered to identify a subset with consistent up or downregulation at each SAHA dose. Histone modifications were characterized in six SAHA dose-responsive genes by chromatin immunoprecipitation (ChIP-RT-qPCR). RESULTS: A large number of genes were shown to be upregulated (N = 657) or downregulated (N = 725) by SAHA in a dose responsive manner (FDR-corrected P-value <= 0.5, fold change >=|2|). Several genes (e.g. CINNAL1, DPEP2, H1F0, IRGM, PHF15, and SELL) are potential in-vivo biomarkers of SAHA activity. SAHA dose-responsive genes included transcription factors, HIV restriction factors, histone methyltransferases, and host proteins that interact with HIV. Pathway analysis suggested net downregulation of T-cell activation with increasing SAHA dose. Histone acetylation was not correlated with host gene expression, but plausible alternative mechanisms for SAHA-modulated gene expression were identified. CONCLUSION: Numerous genes in CD4 T cells are modulated by SAHA in a dose-responsive manner, including genes that may negatively influence HIV activation from latency. Our study suggests that SAHA influences gene expression through a confluence of several mechanisms, including histone modification, and altered expression and activity of transcription factors. PMID- 26258526 TI - Re-engagement in HIV care among mothers living with HIV in South Africa over 36 months post-birth. AB - Prevention of mother-to-child transmission services are integrated into antenatal care in South Africa, but post-birth care is at HIV clinics. Almost all Mothers Living with HIV (MLH) in 24 township neighborhoods (N = 324) reported engagement in HIV care from pregnancy to 36 months post-birth. Less than half re-engaged in HIV care at 6 months (45%), 52.5% at 18 months, and 62.5% at 36 months. Most were prescribed antiretroviral drugs if re-engaged in care, yet only about half (53%) are on antiretroviral drugs at 36 months post-birth. Implementation of Option B+ will require substantially better engagement in care. PMID- 26258525 TI - Incidence of sexually transmitted hepatitis C virus infection in HIV-positive men who have sex with men. AB - OBJECTIVE: The epidemiology of the incidence of sexually transmitted hepatitis C virus (HCV) infection in HIV-positive men who have sex with men (MSM) is only partially understood. In the presence of HIV, HCV infection is more likely to become chronic and liver fibrosis progression is accelerated. DESIGN: A systematic review and meta-analysis was used to synthesize data characterizing sexually transmitted HCV in HIV-positive MSM. METHODS: Electronic and other searches of medical literature (including unpublished reports) were conducted. Eligible studies reported on HCV seroconversion or on reinfection postsuccessful HCV treatment in HIV-positive MSM who were not injecting drugs. Pooled incidence rates were calculated using random-effects meta-analysis, and meta-regression was used to assess study-level moderators. Attributable risk measures were calculated from statistically significant associations between exposures and HCV seroconversion. RESULTS: More than 13 000 HIV-positive MSM in 17 studies were followed for more than 91 000 person-years between 1984 and 2012; the pooled seroconversion rate was 0.53/100 person-years. Calendar time was a significant moderator of HCV seroconversion, increasing from an estimated rate of 0.42/100 person-years in 1991 to 1.09/100 person-years in 2010, and 1.34/100 person-years in 2012. Reinfection postsuccessful HCV treatment (n = 2 studies) was 20 times higher than initial seroconversion rates. Among the seroconverters, a large proportion of infections were attributable to high-risk behaviours including mucosally traumatic sex and sex while high on methamphetamine. CONCLUSION: The high reinfection rates and the attributable risk analysis suggest the existence of a subset of HIV-positive MSM with recurring sexual exposure to HCV. Approaches to HCV control in this population will need to consider the changing epidemiology of HCV infection in MSM. PMID- 26258527 TI - Genetic characterization of multiple hepatitis C virus infections following acute infection in HIV-infected men who have sex with men. AB - OBJECTIVE: High rates of hepatitis C virus (HCV) reinfections among HIV-infected men who have sex with men (MSM) following clearance of a primary infection suggest absence of protective immunity. Here, we investigated the incidence of HCV super and reinfections in 85 HIV-infected MSM with incident HCV infection. DESIGN AND METHODS: Serial sequencing of a fragment of NS5B and the HCV envelope was used to longitudinally characterize the virus. If the primary genotype was still present at the most recent viremic time point, as indicated by the NS5B sequence analysis, serial envelope 2/hypervariable region 1 (E2/HRV1) sequence analysis was performed to distinguish a new infection with the same genotype (clade switch) from intrahost evolution. Incidence rate and cumulative incidence of secondary infections were estimated, and the effect of the primary genotype (1a versus non1) on the risk of acquiring a second infection with the same genotype was determined using Cox proportional-hazards analysis. RESULTS: Among 85 patients with a median follow-up of 4.8 years, incidence rate of secondary infections was 5.39 cases/100 person-years (95% confidence interval 3.34-8.26). Cumulative incidence of genotype switches was markedly higher than the cumulative incidence of clade switches (26.7 versus 4.8% at 5 years, respectively). In patients with HCV-1a as primary infection, the risk for acquiring another HCV-1a infection was reduced compared to those with a primary non-HCV-1a subsequently acquiring HCV-1a (hazard ratio 0.25, 95% confidence interval 0.07-0.93). CONCLUSION: Risk of acquiring a secondary infection with the primary genotype was strikingly reduced compared with the risk of acquiring a secondary infection with a different genotype. PMID- 26258528 TI - Systematic review of the efficacy and safety of intradermal versus intramuscular hepatitis B vaccination in end-stage renal disease population unresponsive to primary vaccination series. AB - INTRODUCTION: The response to hepatitis B vaccine in the dialysis population is reduced compared to the general population. The intradermal (ID) hepatitis B vaccine has been studied as a potential alternative to intramuscular (IM) administration. This alternative route of administration may illicit a response via a distinct immunologic pathway that may help achieve higher seroconversion rates and thus, protection against hepatitis B infection in this vulnerable patient population. METHODS: A literature search was performed in January 2015 using Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials with keywords including, hepatitis B vaccines, intradermal, dermal, intracutaneous, dialysis, hemodialysis, continuous ambulatory peritoneal dialysis, CAPD, peritoneal dialysis, renal failure, chronic renal failure, chronic kidney disease, chronic renal insufficiency, End Stage Renal Disease, ESRD, and CKD. Our search strategy was restricted to human studies published in the English language, and additional literature was retrieved by hand-searching bibliographies of relevant articles. Two reviewers (F.Y. and S.G.) independently reviewed abstracts and/or full texts of articles retrieved from the electronic database using the above-mentioned search strategy. Inclusion criteria were as follows: (1) Published, English-language studies performed in the human population, (2) adult patient population (>=18 years of age), (3) randomized trials, (4) patient population must have been unresponsive to a primary IM hepatitis B vaccination protocol, (5) patients must be chronic dialysis patients, either on maintenance hemodialysis or continuous ambulatory peritoneal dialysis (CAPD), (6) studies that compare IM and ID hepatitis B vaccination-associated seroconversion rates, (7) results must be reported as seroconversion rates at 1 3, 6-9, 12, or 20 months post-vaccination, and (8) seroconversion (protective antibody levels) defined as >10 or >=10 IU/L. RESULTS: Our initial literature review yielded 113 results, of which four were included in our final review. These four prospective trials studied a combined total of 204 dialysis patients. Of these patients, 120 (59%) had received the hepatitis B vaccine intradermally, while 84 (41%) received it intramuscularly. Hepatitis B vaccination type, dose, route, and seroconversion rates were tabulated for each study. Each of the studies used different protocols for patient inclusion, schedule of vaccine administration, and time-points for measuring seroconversion. Seroconversion rates at either 1, 2, 3, 6-9, 12 and/or 20 months were reported. The combined seroconversion rates were 91%, 83%, 86%, 81%, 76%, and 32% at 1, 2, 3, 6-9, 12, and 20 months in the ID group, respectively, and 55%, 72%, 58%, 44%, 24%, and 0% in the IM group, respectively. Chi-square analysis revealed a significantly higher proportion of patients achieving seroconversion in the ID group versus the IM group (p < 0.05). CONCLUSIONS: Our review demonstrates that ID hepatitis B vaccination in primary non-responders undergoing dialysis provides an effective alternative to IM vaccination as a means of protection against hepatitis B infection in this highly susceptible population. Additional well-designed, double blinded, randomized trials are warranted to establish clear guidelines on ID Hepatitis B vaccine dose and duration of vaccination schedule. PMID- 26258529 TI - Current evidence on whether perinatal risk factors influence coeliac disease is circumstantial. AB - Coeliac disease is triggered by an interplay of environmental and genetic factors and is one of the most prevalent autoimmune diseases in children, occurring in about 1% of Europeans. Over the last few decades, there has been a growing interest in the role of the perinatal environment in coeliac disease and this review discusses the growing body of literature on coeliac disease and perinatal risk factors. CONCLUSION: There is still only circumstantial evidence that the perinatal environment influences coeliac disease development. Large-scale cohort studies and emerging scientific concepts, such as epigenetics, may help us establish the role of these environmental factors. PMID- 26258530 TI - Kidney Dysfunction in Adult Offspring Exposed In Utero to Type 1 Diabetes Is Associated with Alterations in Genome-Wide DNA Methylation. AB - BACKGROUND: Fetal exposure to hyperglycemia impacts negatively kidney development and function. OBJECTIVE: Our objective was to determine whether fetal exposure to moderate hyperglycemia is associated with epigenetic alterations in DNA methylation in peripheral blood cells and whether those alterations are related to impaired kidney function in adult offspring. DESIGN: Twenty nine adult, non diabetic offspring of mothers with type 1 diabetes (T1D) (case group) were matched with 28 offspring of T1D fathers (control group) for the study of their leukocyte genome-wide DNA methylation profile (27,578 CpG sites, Human Methylation 27 BeadChip, Illumina Infinium). In a subset of 19 cases and 18 controls, we assessed renal vascular development by measuring Glomerular Filtration Rate (GFR) and Effective Renal Plasma Flow (ERPF) at baseline and during vasodilatation produced by amino acid infusion. RESULTS: Globally, DNA was under-methylated in cases vs. controls. Among the 87 CpG sites differently methylated, 74 sites were less methylated and 13 sites more methylated in cases vs. controls. None of these CpG sites were located on a gene known to be directly involved in kidney development and/or function. However, the gene encoding DNA methyltransferase 1 (DNMT1)--a key enzyme involved in gene expression during early development--was under-methylated in cases. The average methylation of the 74 under-methylated sites differently correlated with GFR in cases and controls. CONCLUSION: Alterations in methylation profile imprinted by the hyperglycemic milieu of T1D mothers during fetal development may impact kidney function in adult offspring. The involved pathways seem to be a nonspecific imprinting process rather than specific to kidney development or function. PMID- 26258532 TI - On the Agreement between Manual and Automated Methods for Single-Trial Detection and Estimation of Features from Event-Related Potentials. AB - The agreement between humans and algorithms on whether an event-related potential (ERP) is present or not and the level of variation in the estimated values of its relevant features are largely unknown. Thus, the aim of this study was to determine the categorical and quantitative agreement between manual and automated methods for single-trial detection and estimation of ERP features. To this end, ERPs were elicited in sixteen healthy volunteers using electrical stimulation at graded intensities below and above the nociceptive withdrawal reflex threshold. Presence/absence of an ERP peak (categorical outcome) and its amplitude and latency (quantitative outcome) in each single-trial were evaluated independently by two human observers and two automated algorithms taken from existing literature. Categorical agreement was assessed using percentage positive and negative agreement and Cohen's kappa, whereas quantitative agreement was evaluated using Bland-Altman analysis and the coefficient of variation. Typical values for the categorical agreement between manual and automated methods were derived, as well as reference values for the average and maximum differences that can be expected if one method is used instead of the others. Results showed that the human observers presented the highest categorical and quantitative agreement, and there were significantly large differences between detection and estimation of quantitative features among methods. In conclusion, substantial care should be taken in the selection of the detection/estimation approach, since factors like stimulation intensity and expected number of trials with/without response can play a significant role in the outcome of a study. PMID- 26258533 TI - Macro-particle charcoal C content following prescribed burning in a mixed-conifer forest, Sierra Nevada, California. AB - Fire suppression and changing climate have resulted in increased large wildfire frequency and severity in the western United States, causing carbon cycle impacts. Forest thinning and prescribed burning reduce high-severity fire risk, but require removal of biomass and emissions of carbon from burning. During each fire a fraction of the burning vegetation and soil organic matter is converted into charcoal, a relatively stable carbon form. We sought to quantify the effects of pre-fire fuel load and type on charcoal carbon produced by biomass combusted in a prescribed burn under different thinning treatments and to identify more easily measured predictors of charcoal carbon mass in a historically frequent fire mixed-conifer forest. We hypothesized that charcoal carbon produced from coarse woody debris (CWD) during prescribed burning would be greater than that produced from fine woody debris (FWD). We visually quantified post-treatment charcoal carbon content in the O-horizon and the A-horizon beneath CWD (> 30 cm diameter) and up to 60 cm from CWD that was present prior to treatment. We found no difference in the size of charcoal carbon pools from CWD (treatment means ranged from 0.3-2.0 g m-2 of A-horizon and 0.0-1.7 g m-2 of O-horizon charcoal) and FWD (treatment means ranged from 0.2-1.7 g m-2 of A-horizon and 0.0-1.5 g m-2 of O-horizon charcoal). We also compared treatments and found that the burn-only, understory-thin and burn, and overstory-thin and burn treatments had significantly more charcoal carbon than the control. Charcoal carbon represented 0.29% of total ecosystem carbon. We found that char mass on CWD was an important predictor of charcoal carbon mass, but only explained 18-35% of the variation. Our results help improve our understanding of the effects forest restoration treatments have on ecosystem carbon by providing additional information about charcoal carbon content. PMID- 26258534 TI - A Study of the First Year of the End-of-Life Clinic for Physician-Assisted Dying in the Netherlands. AB - IMPORTANCE: Right to Die NL, an organization in the Netherlands that advocates for the option of euthanasia, founded the End-of-Life Clinic in 2012 to provide euthanasia or physician-assisted suicide for patients who meet all legal requirements but whose regular physicians rejected their request. Many patients whose requests are rejected have less common situations, such as a psychiatric or psychological condition, dementia, or being tired of living. OBJECTIVE: To study outcomes of requests for euthanasia or physician-assisted suicide received by the clinic and factors associated with granting or rejecting requests. DESIGN: Analysis of application forms and registration files from March 1, 2012, to March 1, 2013, the clinic's first year of operation, for 645 patients who applied to the clinic with a request for euthanasia or physician-assisted suicide and whose cases were concluded during the study period. MAIN OUTCOMES AND MEASURES: A request could be granted, rejected, or withdrawn or the patient could have died before a final decision was reached. We analyzed bivariate and multivariate associations with medical conditions, type of suffering, and sociodemographic variables. RESULTS: Of the 645 requests made by patients, 162 requests (25.1%) were granted, 300 requests (46.5%) were refused, 124 patients (19.2%) died before the request could be assessed, and 59 patients (9.1%) withdrew their requests. Patients with a somatic condition (113 of 344 [32.8%]) or with cognitive decline (21 of 56 [37.5%]) had the highest percentage of granted requests. Patients with a psychological condition had the smallest percentage of granted requests. Six (5.0%) of 121 requests from patients with a psychological condition were granted, as were 11 (27.5%) of 40 requests from patients who were tired of living. CONCLUSIONS AND RELEVANCE: Physicians in the Netherlands have more reservations about less common reasons that patients request euthanasia and physician-assisted suicide, such as psychological conditions and being tired of living, than the medical staff working for the End-of-Life Clinic. The physicians and nurses employed by the clinic, however, often confirmed the assessment of the physician who previously cared for the patient; they rejected nearly half of the requests for euthanasia and physician-assisted suicide, possibly because the legal due care criteria had not been met. PMID- 26258535 TI - Electronic Structure of Ru2(II,II) Oxypyridinates: Synthetic, Structural, and Theoretical Insights into Axial Ligand Binding. AB - Reduction of (4,0)-Ru2(chp)4Cl (1) (chp = 6-chloro-2-oxypyridinate) with Zn or FeCl2 yields a series of axial ligand adducts of the Ru2(II,II) species Ru2(chp)4(L), with L = tetrahydrofuran (2), dimethyl sulfoxide (DMSO; 3), PPh3 (4), pyridine (5), or MeCN (6). Zn reduction in noncoordinating solvents such as toluene or CH2Cl2 leads to the dimeric species [Ru2(chp)4]2 (7) or [Ru2(chp)4]2(ZnCl2) (8), whereas addition of strongly sigma-donating ligands such as CO causes cleavage of the Ru-Ru bond. Density functional theory (DFT) models of these complexes, the axially free species, and the axial adducts of several other potential ligands (H2O, NH3, CH2Cl2, S-bound DMSO, N2, and CO) indicate that these compounds can be divided into three distinct categories, based on their Ru-Ru bond length and electronic structure. Compounds 2, 3, 5, 6, 7, and 8, the hypothetical axially free species, and adducts of H2O and NH3 fit in Category 1 with a (delta*)(2)(pi*)(2) ground state, as indicated by their electronic spectra, magnetic properties, and Ru-Ru bond distances. However, compound 4 and the CH2Cl2 adduct (Category 2) show a pseudo-Jahn-Teller distortion and spectroscopic signs of delta*/pi* orbital mixing suggestive of a new electronic ground state intermediate between the (delta*)(2)(pi*)(2) and (delta*)(1)(pi*)(3) configurations. Category 3 consists of the hypothetical adducts of N2, S-bound DMSO, and CO, all of which are predicted to have a (delta*)(1)(pi*)(3) configuration. Electronic spectra were recorded and assigned using time-dependent DFT, allowing assignment of a band in the 10,000-13,000 cm(-1) range as the delta -> pi* transition. The axial ligand's pi-acid character heavily influences the delta*-pi* gap, and thereby the ground-state electronic configuration, but not the axial ligand binding strength, which is dictated more by the sigma-donor character of the ligands. Thus, this work greatly expands the number of axial ligand adducts known for Ru2(II,II) complexes supported by N,O-donor ligands and provides a predictive theoretical framework for their stability and electronic structures. PMID- 26258536 TI - A meta-analytic approach to examining the correlation between religion/spirituality and mental health in cancer. AB - Religion and spirituality (R/S) are patient-centered factors and often are resources for managing the emotional sequelae of the cancer experience. Studies investigating the correlation between R/S (eg, beliefs, experiences, coping) and mental health (eg, depression, anxiety, well being) in cancer have used very heterogeneous measures and have produced correspondingly inconsistent results. A meaningful synthesis of these findings has been lacking; thus, the objective of this review was to conduct a meta-analysis of the research on R/S and mental health. Four electronic databases were systematically reviewed, and 2073 abstracts met initial selection criteria. Reviewer pairs applied standardized coding schemes to extract indices of the correlation between R/S and mental health. In total, 617 effect sizes from 148 eligible studies were synthesized using meta-analytic generalized estimating equations, and subgroup analyses were performed to examine moderators of effects. The estimated mean correlation (Fisher z) was 0.19 (95% confidence interval [CI], 0.16-0.23), which varied as a function of R/S dimensions: affective R/S (z = 0.38; 95% CI, 0.33-0.43), behavioral R/S (z = 0.03; 95% CI, -0.02-0.08), cognitive R/S (z = 0.10; 95% CI, 0.06-0.14), and 'other' R/S (z = 0.08; 95% CI, 0.03-0.13). Aggregate, study-level demographic and clinical factors were not predictive of the relation between R/S and mental health. There was little indication of publication or reporting biases. The correlation between R/S and mental health generally was positive. The strength of that correlation was modest and varied as a function of the R/S dimensions and mental health domains assessed. The identification of optimal R/S measures and more sophisticated methodological approaches are needed to advance research. PMID- 26258537 TI - MicroRNA and transcription factor mediated regulatory network analysis reveals critical regulators and regulatory modules in myocardial infarction. AB - Myocardial infarction (MI) is a severe coronary artery disease and a leading cause of mortality and morbidity worldwide. However, the molecular mechanisms of MI have yet to be fully elucidated. In this study, we compiled MI-related genes, MI-related microRNAs (miRNAs) and known human transcription factors (TFs), and we then identified 1,232 feed-forward loops (FFLs) among these miRNAs, TFs and their co-regulated target genes through integrating target prediction. By merging these FFLs, the first miRNA and TF mediated regulatory network for MI was constructed, from which four regulators (SP1, ESR1, miR-21-5p and miR-155-5p) and three regulatory modules that might play crucial roles in MI were then identified. Furthermore, based on the miRNA and TF mediated regulatory network and literature survey, we proposed a pathway model for miR-21-5p, the miR-29 family and SP1 to demonstrate their potential co-regulatory mechanisms in cardiac fibrosis, apoptosis and angiogenesis. The majority of the regulatory relations in the model were confirmed by previous studies, which demonstrated the reliability and validity of this miRNA and TF mediated regulatory network. Our study will aid in deciphering the complex regulatory mechanisms involved in MI and provide putative therapeutic targets for MI. PMID- 26258539 TI - Genetic variants in GAPDH confer susceptibility to sporadic Parkinson's disease in a Chinese Han population. AB - BACKGROUND: Accumulating evidence has demonstrated that the glyceraldehyde-3 phosphate dehydrogenase (GAPDH) is a part of Lewy body inclusions and involves the pathogenesis of Parkinson's disease (PD). However, it remains unknown whether or not genetic variation at the GAPDH locus contributes to the risk for PD. METHODS: A total of 302 sporadic PD patients and 377 control subjects were recruited in our study for assessing two single nucleotide polymorphisms (rs3741918 and rs1060619) in the GAPDH gene. Both allelic association and additive models were used to analyze association between GAPDH variants and risk for PD. RESULTS: Both polymorphisms were significantly associated with risk for PD after correction by Bonferroni multiple testing. The minor allele of rs3741918 was associated with decreased risk of sporadic PD (allelic contrast, OR = 0.74, 95% CI: 0.59-0.93, corrected P = 0.028; additive model, OR = 0.73, 95% CI: 0.58 0.92, corrected P = 0.018). While for the rs1060619 locus, the minor allele conferred increased risk for PD (allelic contrast, OR = 1.41, 95% CI: 1.14-1.75, corrected P = 0.007; additive model, OR = 1.43, 95% CI: 1.15-1.79, corrected P = 0.002). CONCLUSION: Our study indicates that GAPDH variants confer susceptibility to sporadic PD in a Chinese Han population, which is consistent with the role of GAPDH protein in neuronal apoptosis. To our knowledge, this is the first study of genetic association between GAPDH locus and risk for PD in the Chinese population. PMID- 26258541 TI - A scalable and operationally simple radical trifluoromethylation. AB - The large number of reagents that have been developed for the synthesis of trifluoromethylated compounds is a testament to the importance of the CF3 group as well as the associated synthetic challenge. Current state-of-the-art reagents for appending the CF3 functionality directly are highly effective; however, their use on preparative scale has minimal precedent because they require multistep synthesis for their preparation, and/or are prohibitively expensive for large scale application. For a scalable trifluoromethylation methodology, trifluoroacetic acid and its anhydride represent an attractive solution in terms of cost and availability; however, because of the exceedingly high oxidation potential of trifluoroacetate, previous endeavours to use this material as a CF3 source have required the use of highly forcing conditions. Here we report a strategy for the use of trifluoroacetic anhydride for a scalable and operationally simple trifluoromethylation reaction using pyridine N-oxide and photoredox catalysis to affect a facile decarboxylation to the CF3 radical. PMID- 26258542 TI - Anti-transcription intermediary factor-1gamma/alpha/beta antibody-positive dermatomyositis associated with multiple panniculitis lesions. PMID- 26258543 TI - Response Assessment of Thermal Papers from Four Continents to Fingerprint Development by Heat. AB - Latent fingerprint deposits on thermal paper sourced from the U.S., China, the U.K., and Australia have been visualized by heating. U.S. and Chinese sourced paper produced two distinct types of fingerprint development. In one type (type 1), the paper dye colors where the deposit is present (as previously reported) and in the other type (type 2) the 'inverse' of this gives paper coloring only in areas not coincident with the deposit. Both development types gave identifiable fingerprints, the majority fading within 24 h of heating. Fingerprint development from U.K. and Australian sourced paper was exclusively type 1 and resistant to fading. Temperatures for fingerprint visualization were higher for U.S. paper (64 71 degrees C) and Chinese paper (75-95 degrees C) than for U.K. and Australian sourced paper (43-50 degrees C). Particularly for Chinese sourced paper, these temperatures were within a few degrees of the normal paper color temperature. A mechanism for type 2 fingerprint development is proposed. PMID- 26258538 TI - Prediction of human population responses to toxic compounds by a collaborative competition. AB - The ability to computationally predict the effects of toxic compounds on humans could help address the deficiencies of current chemical safety testing. Here, we report the results from a community-based DREAM challenge to predict toxicities of environmental compounds with potential adverse health effects for human populations. We measured the cytotoxicity of 156 compounds in 884 lymphoblastoid cell lines for which genotype and transcriptional data are available as part of the Tox21 1000 Genomes Project. The challenge participants developed algorithms to predict interindividual variability of toxic response from genomic profiles and population-level cytotoxicity data from structural attributes of the compounds. 179 submitted predictions were evaluated against an experimental data set to which participants were blinded. Individual cytotoxicity predictions were better than random, with modest correlations (Pearson's r < 0.28), consistent with complex trait genomic prediction. In contrast, predictions of population level response to different compounds were higher (r < 0.66). The results highlight the possibility of predicting health risks associated with unknown compounds, although risk estimation accuracy remains suboptimal. PMID- 26258540 TI - Joint MiRNA/mRNA expression profiling reveals changes consistent with development of dysfunctional corpus luteum after weight gain. AB - Obese women exhibit decreased fertility, high miscarriage rates and dysfunctional corpus luteum (CL), but molecular mechanisms are poorly defined. We hypothesized that weight gain induces alterations in CL gene expression. RNA sequencing was used to identify changes in the CL transcriptome in the vervet monkey (Chlorocebus aethiops) during weight gain. 10 months of high-fat, high-fructose diet (HFHF) resulted in a 20% weight gain for HFHF animals vs. 2% for controls (p = 0.03) and a 66% increase in percent fat mass for HFHF group. Ovulation was confirmed at baseline and after intervention in all animals. CL were collected on luteal day 7-9 based on follicular phase estradiol peak. 432 mRNAs and 9 miRNAs were differentially expressed in response to HFHF diet. Specifically, miR-28, miR 26, and let-7b previously shown to inhibit sex steroid production in human granulosa cells, were up-regulated. Using integrated miRNA and gene expression analysis, we demonstrated changes in 52 coordinately regulated mRNA targets corresponding to opposite changes in miRNA. Specifically, 2 targets of miR-28 and 10 targets of miR-26 were down-regulated, including genes linked to follicular development, steroidogenesis, granulosa cell proliferation and survival. To the best of our knowledge, this is the first report of dietary-induced responses of the ovulating ovary to developing adiposity. The observed HFHF diet-induced changes were consistent with development of a dysfunctional CL and provide new mechanistic insights for decreased sex steroid production characteristic of obese women. MiRNAs may represent novel biomarkers of obesity-related subfertility and potential new avenues for therapeutic intervention. PMID- 26258544 TI - Neuronal Gonadotrophin-Releasing Hormone (GnRH) and Astrocytic Gonadotrophin Inhibitory Hormone (GnIH) Immunoreactivity in the Adult Rat Hippocampus. AB - Gonadotrophin-releasing hormone (GnRH) and gonadotrophin inhibitory hormone (GnIH) are neuropeptides secreted by the hypothalamus that regulate reproduction. GnRH receptors are not only present in the anterior pituitary, but also are abundantly expressed in the hippocampus of rats, suggesting that GnRH regulates hippocampal function. GnIH inhibits pituitary gonadotrophin secretion and is also expressed in the hippocampus of a songbird; its role outside of the reproductive axis is not well established. In the present study, we employed immunohistochemistry to examine three forms of GnRH [mammalian GnRH-I (mGnRH-I), chicken GnRH-II (cGnRH-II) and lamprey GnRH-III (lGnRH-III)] and GnIH in the adult rat hippocampus. No mGnRH-I and cGnRH-II+ cell bodies were present in the hippocampus. Sparse mGnRH-I and cGnRH-II+ fibres were present within the CA1 and CA3 fields of the hippocampus, along the hippocampal fissure, and within the hilus of the dentate gyrus. No lGnRH-III was present in the rodent hippocampus. GnIH-immunoreactivity was present in the hippocampus in cell bodies that resembled astrocytes. Males had more GnIH+ cells in the hilus of the dentate gyrus than females. To confirm the GnIH+ cell body phenotype, we performed double label immunofluorescence against GnIH, glial fibrillary acidic protein (GFAP) and NeuN. Immunofluorescence revealed that all GnIH+ cell bodies in the hippocampus also contained GFAP, a marker of astrocytes. Taken together, these data suggest that GnRH does not reach GnRH receptors in the rat hippocampus primarily via synaptic release. By contrast, GnIH might be synthesised locally in the rat hippocampus by astrocytes. These data shed light on the sites of action and possible functions of GnRH and GnIH outside of the hypothalamic-pituitary-gonadal axis. PMID- 26258545 TI - Inattentional Blindness and Individual Differences in Cognitive Abilities. AB - People sometimes fail to notice salient unexpected objects when their attention is otherwise occupied, a phenomenon known as inattentional blindness. To explore individual differences in inattentional blindness, we employed both static and dynamic tasks that either presented the unexpected object away from the focus of attention (spatial) or near the focus of attention (central). We hypothesized that noticing in central tasks might be driven by the availability of cognitive resources like working memory, and that noticing in spatial tasks might be driven by the limits on spatial attention like attention breadth. However, none of the cognitive measures predicted noticing in the dynamic central task or in either the static or dynamic spatial task. Only in the central static task did working memory capacity predict noticing, and that relationship was fairly weak. Furthermore, whether or not participants noticed an unexpected object in a static task was only weakly associated with their odds of noticing an unexpected object in a dynamic task. Taken together, our results are largely consistent with the notion that noticing unexpected objects is driven more by stochastic processes common to all people than by stable individual differences in cognitive abilities. PMID- 26258546 TI - Protein kinase A activity is necessary for fission and fusion of Golgi to endoplasmic reticulum retrograde tubules. AB - It is becoming increasingly accepted that together with vesicles, tubules play a major role in the transfer of cargo between different cellular compartments. In contrast to our understanding of the molecular mechanisms of vesicular transport, little is known about tubular transport. How signal transduction molecules regulate these two modes of membrane transport processes is also poorly understood. In this study we investigated whether protein kinase A (PKA) activity regulates the retrograde, tubular transport of Golgi matrix proteins from the Golgi to the endoplasmic reticulum (ER). We found that Golgi-to-ER retrograde transport of the Golgi matrix proteins giantin, GM130, GRASP55, GRASP65, and p115 was impaired in the presence of PKA inhibitors. In addition, we unexpectedly found accumulation of tubules containing both Golgi matrix proteins and resident Golgi transmembrane proteins. These tubules were still attached to the Golgi and were highly dynamic. Our data suggest that both fission and fusion of retrograde tubules are mechanisms regulated by PKA activity. PMID- 26258547 TI - Retinal Nerve Fiber and Optic Disc Morphology in Patients with Human Immunodeficiency Virus Using the Heidelberg Retina Tomography 3. AB - PURPOSE: To use novel confocal scanning ophthalmoscopy technology to test hypothesis that HIV-seropositive patients without history of retinitis with a history of a low CD4 count are more likely to have damage to their retinal nerve fiber layer (RNFL) when compared to patients with high CD4 count. In addition, we compared optic disc morphologic changes with glaucoma. DESIGN: Cross-sectional study. PARTICIPANTS AND CONTROLS: 171 patients were divided into four groups. The control group consisted of 40 eyes of 20 HIV-seronegative patients. The second group consisted of 80 eyes of 41 HIV-positive patients whose CD4 cell count never dropped below 100 (1.0 x 10(9)/L). The third group consisted of 44 eyes of 26 HIV positive patients with a history of low CD4 counts <100. Fourth group consisted of 79 eyes of 79 patients with confirmed glaucoma who served as positive controls. TESTING: Confocal scanning laser ophthalmoscopy was performed with the Heidelberg Retina Tomograph (HRT3) and data were analyzed with HRT3, software (Heyex version 1.5.10.0). MAIN OUTCOME MEASURES: Disc area, cup area, cup volume, rim volume, mean cup depth, maximum cup depth, cup-to-disc ration, mean RNFL thickness, and RNFL cross-sectional area. RESULTS: Analysis of the global optic nerve and cup parameters showed no difference in disk area among the four groups. There was also no difference in cup, rim volume, mean cup depth, or maximum cup depth among the first three groups but they were all different from glaucoma group. The RNFL was thinner in glaucoma and both HIV-positive groups compared to HIV-seronegative subjects. The cross sectional RNFL area was thinner in both high and low CD4 HIV-positive groups compared to HIV-seronegative group in the nasal and temporal/inferior sectors, respectively. Glaucoma group showed thinning in all sectors. CONCLUSIONS: HIV retinopathy results in retinal nerve fiber layer loss without structural optic nerve supportive tissue change. RNFL damage may occur early in HIV disease by mechanism different than in glaucoma. PMID- 26258548 TI - Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa. AB - Around 2.5 million HIV-infected individuals failing first-line therapy qualify for boosted protease inhibitor (bPI)-based second-line therapy globally. Major resistance mutations are rarely present at treatment failure in patients receiving bPI and the determinants of failure in these patients remain unknown. There is evidence that Gag can impact PI susceptibility. Here, we have sequenced Gag-Protease before and following failure in 23 patients in the SARA trial infected with subtypes A, C, and D viruses. Before bPI, significant variation in Protease and Gag was observed at positions previously associated with PI exposure and resistance including Gag mutations L449P, S451N, and L453P and Protease K20I and L63P. Following PI failure, previously described mutations in Protease and Gag were observed, including those at the cleavage sites such as R361K and P453L. However, the emergence of clear genetic determinants of therapy failure across patients was not observed. Larger Gag sequence datasets will be required to comprehensively identify mutational correlates of bPI failure across subtypes. PMID- 26258549 TI - Fourier magnetic imaging with nanoscale resolution and compressed sensing speed up using electronic spins in diamond. AB - Optically detected magnetic resonance using nitrogen-vacancy (NV) colour centres in diamond is a leading modality for nanoscale magnetic field imaging, as it provides single electron spin sensitivity, three-dimensional resolution better than 1 nm (ref. 5) and applicability to a wide range of physical and biological samples under ambient conditions. To date, however, NV-diamond magnetic imaging has been performed using 'real-space' techniques, which are either limited by optical diffraction to ~250 nm resolution or require slow, point-by-point scanning for nanoscale resolution, for example, using an atomic force microscope, magnetic tip, or super-resolution optical imaging. Here, we introduce an alternative technique of Fourier magnetic imaging using NV-diamond. In analogy with conventional magnetic resonance imaging (MRI), we employ pulsed magnetic field gradients to phase-encode spatial information on NV electronic spins in wavenumber or 'k-space' followed by a fast Fourier transform to yield real-space images with nanoscale resolution, wide field of view and compressed sensing speed up. PMID- 26258550 TI - Opto-nanomechanical spectroscopic material characterization. AB - The non-destructive, simultaneous chemical and physical characterization of materials at the nanoscale is an essential and highly sought-after capability. However, a combination of limitations imposed by Abbe diffraction, diffuse scattering, unknown subsurface, electromagnetic fluctuations and Brownian noise, for example, have made achieving this goal challenging. Here, we report a hybrid approach for nanoscale material characterization based on generalized nanomechanical force microscopy in conjunction with infrared photoacoustic spectroscopy. As an application, we tackle the outstanding problem of spatially and spectrally resolving plant cell walls. Nanoscale characterization of plant cell walls and the effect of complex phenotype treatments on biomass are challenging but necessary in the search for sustainable and renewable bioenergy. We present results that reveal both the morphological and compositional substructures of the cell walls. The measured biomolecular traits are in agreement with the lower-resolution chemical maps obtained with infrared and confocal Raman micro-spectroscopies of the same samples. These results should prove relevant in other fields such as cancer research, nanotoxicity, and energy storage and production, where morphological, chemical and subsurface studies of nanocomposites, nanoparticle uptake by cells and nanoscale quality control are in demand. PMID- 26258552 TI - "Stirred, Not Shaken": Vibrational Coherence Can Speed Up Electronic Absorption. AB - We have recently proposed a laser control scheme for ultrafast absorption in multilevel systems by parallel transfer (J. Phys. Chem. Lett. 2015, 6, 1724). In this work we develop an analytical model that better takes into account the main features of electronic absorption in molecules. We show that the initial vibrational coherence in the ground electronic state can be used to greatly enhance the rate and yield of absorption when ultrashort pulses are used, provided that the phases of the coherences are taken into account. On the contrary, the initial coherence plays no role in the opposite limit, when a single long pulse drives the optical transition. The theory is tested by numerical simulations in the first absorption band of Na2. PMID- 26258551 TI - Initial Reaction Mechanism of Platinum Nanoparticle in Methanol-Water System and the Anomalous Catalytic Effect of Water. AB - Understanding the detailed reaction mechanism in the early stage of noble metal nanoparticles is very critical for controlling the final crystal's size, morphology, and properties. Here, we report a systematic study on the initial reaction mechanism of Pt nanoparticles in methanol-water system and demonstrate an anomalous catalytic effect of H2O on the reduction of H2PtCl6 to Pt nanoparticles using a combination of UV-vis, X-ray absorption spectroscopy (XAS), liquid chromatography mass spectrometry (LCMS), and first-principles calculation methods. The observations reveal the transformation route [PtCl6](2-) -> [PtCl5(CH3O)](2-) -> [PtCl4](2-) -> [PtCl3(CH3O)](2-) -> [PtCl2](2-) and finally to form Pt nanoparticles in a pure CH3OH solution. With 10 vol % water adding in the CH3OH solution, a new and distinct chemical reduction pathway is found in which the precursors change from [PtCl6](2-) to [PtCl5(CH3O)(H2O)](2-) to [PtCl4](2-) to [PtCl3(CH3O)(H2O)](2-) to [PtCl2](2-) and to Pt nanoparticles. Notably, the supernumerary water molecular can significantly accelerate the rate of chemical reduction and greatly shorten the reaction time. This work not only elucidates the initial reaction mechanism of Pt nanoparticles but also highlights the pronounced influence of H2O on the reaction pathway, which will provide useful insights for understanding the formation mechanism of noble metal nanoparticles and open up a high efficient way to synthesize new functional nanomaterial. PMID- 26258553 TI - Role of Telokin in Regulating Murine Gastric Fundus Smooth Muscle Tension. AB - Telokin phosphorylation by cyclic GMP-dependent protein kinase facilitates smooth muscle relaxation. In this study we examined the relaxation of gastric fundus smooth muscles from basal tone, or pre-contracted with KCl or carbachol (CCh), and the phosphorylation of telokin S13, myosin light chain (MLC) S19, MYPT1 T853, T696, and CPI-17 T38 in response to 8-Bromo-cGMP, the NO donor sodium nitroprusside (SNP), or nitrergic neurotransmission. We compared MLC phosphorylation and the contraction and relaxation responses of gastric fundus smooth muscles from telokin-/- mice and their wild-type littermates to KCl or CCh, and 8-Bromo-cGMP, SNP, or nitrergic neurotransmission, respectively. We compared the relaxation responses and telokin phosphorylation of gastric fundus smooth muscles from wild-type mice and W/WV mice which lack ICC-IM, to 8-Bromo cGMP, SNP, or nitrergic neurotransmission. We found that telokin S13 is basally phosphorylated and that 8-Bromo-cGMP and SNP increased basal telokin phosphorylation. In muscles pre-contracted with KCl or CCh, 8-Bromo-cGMP and SNP had no effect on CPI-17 or MYPT1 phosphorylation, but increased telokin phosphorylation and reduced MLC phosphorylation. In telokin-/- gastric fundus smooth muscles, basal tone and constitutive MLC S19 phosphorylation were increased. Pre-contracted telokin-/- gastric fundus smooth muscles have increased contractile responses to KCl, CCh, or cholinergic neurotransmission and reduced relaxation to 8-Bromo-cGMP, SNP, and nitrergic neurotransmission. However, basal telokin phosphorylation was not increased when muscles were stimulated with lower concentrations of SNP or when the muscles were stimulated by nitrergic neurotransmission. SNP, but not nitrergic neurotransmission, increased telokin Ser13 phosphorylation in both wild-type and W/WV gastric fundus smooth muscles. Our findings indicate that telokin may play a role in attenuating constitutive MLC phosphorylation and provide an additional mechanism to augment gastric fundus mechanical responses to inhibitory neurotransmission. PMID- 26258554 TI - Gender Determination of Adult Individuals by Three-Dimensional Modeling of Canines. AB - Gender determination is a fundamental issue in forensic anthropology. Many techniques based on bone and dental remains have been proposed. It is not always possible to implement the techniques using bones, but teeth are often perfectly preserved. It has been demonstrated that the canine has the greatest sexual dimorphism, and the aim of this work was to provide an easy and accurate dental technique for determining the gender in the absence of other skeletal elements. The sample was composed of 210 CT scans with four healthy canines. The 840 canines were modeled using MIMICS(r) 10.01 software. The total volume of each tooth was determined. Seven mathematical models were determined by binary logistic regressions and ranked in order of relative performance. The seven proposed predictive models thus performed (0.910<=AUC<=0.938), with overall rates of correct predictions between 82.38 and 85.24%. The 4-canine model is the most powerful for predicting the gender. PMID- 26258555 TI - Corticosteroid Therapy for Patients Hospitalized With Community-Acquired Pneumonia: A Systematic Review and Meta-analysis. AB - BACKGROUND: Community-acquired pneumonia (CAP) is common and often severe. PURPOSE: To examine the effect of adjunctive corticosteroid therapy on mortality, morbidity, and duration of hospitalization in patients with CAP. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through 24 May 2015. STUDY SELECTION: Randomized trials of systemic corticosteroids in hospitalized adults with CAP. DATA EXTRACTION: Two reviewers independently extracted study data and assessed risk of bias. Quality of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation system by consensus among the authors. DATA SYNTHESIS: The median age was typically in the 60s, and approximately 60% of patients were male. Adjunctive corticosteroids were associated with possible reductions in all-cause mortality (12 trials; 1974 patients; risk ratio [RR], 0.67 [95% CI, 0.45 to 1.01]; risk difference [RD], 2.8%; moderate certainty), need for mechanical ventilation (5 trials; 1060 patients; RR, 0.45 [CI, 0.26 to 0.79]; RD, 5.0%; moderate certainty), and the acute respiratory distress syndrome (4 trials; 945 patients; RR, 0.24 [CI, 0.10 to 0.56]; RD, 6.2%; moderate certainty). They also decreased time to clinical stability (5 trials; 1180 patients; mean difference, -1.22 days [CI, -2.08 to -0.35 days]; high certainty) and duration of hospitalization (6 trials; 1499 patients; mean difference, -1.00 day [CI, -1.79 to -0.21 days]; high certainty). Adjunctive corticosteroids increased frequency of hyperglycemia requiring treatment (6 trials; 1534 patients; RR, 1.49 [CI, 1.01 to 2.19]; RD, 3.5%; high certainty) but did not increase frequency of gastrointestinal hemorrhage. LIMITATIONS: There were few events and trials for many outcomes. Trials often excluded patients at high risk for adverse events. CONCLUSION: For hospitalized adults with CAP, systemic corticosteroid therapy may reduce mortality by approximately 3%, need for mechanical ventilation by approximately 5%, and hospital stay by approximately 1 day. PRIMARY FUNDING SOURCE: None. PMID- 26258556 TI - Characterization of particulate-bound PAHs in rural households using different types of domestic energy in Henan Province, China. AB - The concentrations and composition of sixteen PAHs adsorbed to respirable particulate matter (PM10<=10 MUm) and inhalable particulate matter (PM2.5<=2.5 MUm) were determined during autumn and winter in rural households of Henan Province, China, which used four types of domestic energy [crop residues, coal, liquid petroleum gas (LPG) and electricity] for cooking and heating. The present results show that there were significantly (p<0.05) seasonal variations of particulate-bound PAHs in the rural households. The daily mean concentrations of particulate-bound PAHs in the kitchens, sitting rooms and outdoors were apparently higher in winter than those in autumn, except those in the kitchens using coal. The present study also shows that there were obvious variations of particulate-bound PAHs among the four types of domestic energy used in the rural households. The households using LPG for cooking can, at least in some circumstances, have higher concentrations of PAHs in the kitchens than using crop residues or electricity. In addition, using coal in the sitting rooms seemed to result in apparently higher concentrations of particulate-bound PAHs than using the other three types of domestic energy during winter. The most severe contamination occurred in the kitchens using LPG in winter, where the daily mean concentrations of PM2.5-bound PAHs were up to 762.5+/-931.2 ng m(-3), indicating that there was serious health risk of inhalation exposure to PAHs in the rural households of Henan Province. Rural residents' exposure to PM2.5-bound PAHs in kitchens would be roughly reduced by 69.8% and 85.5% via replacing coal or crop residues with electricity in autumn. The pilot research would provide important supplementary information to the indoor air pollution studies in rural area. PMID- 26258557 TI - Increasing pressure on freshwater resources due to terrestrial feed ingredients for aquaculture production. AB - As aquaculture becomes more important for feeding the growing world population, so too do the required natural resources needed to produce aquaculture feed. While there is potential to replace fish meal and fish oil with terrestrial feed ingredients, it is important to understand both the positive and negative implications of such a development. The use of feed with a large proportion of terrestrial feed may reduce the pressure on fisheries to provide feed for fish, but at the same time it may significantly increase the pressure on freshwater resources, due to water consumption and pollution in crop production for aquafeed. Here the green, blue and gray water footprint of cultured fish and crustaceans related to the production of commercial feed for the year 2008 has been determined for the major farmed species, representing 88% of total fed production. The green, blue and gray production-weighted average feed water footprints of fish and crustaceans fed commercial aquafeed are estimated at 1629 m3/t, 179 m3/t and 166 m3/t, respectively. The estimated global total water footprint of commercial aquafeed was 31-35 km3 in 2008. The top five contributors to the total water footprint of commercial feed are Nile tilapia, Grass carp, Whiteleg shrimp, Common carp and Atlantic salmon, which together have a water footprint of 18.2 km3. An analysis of alternative diets revealed that the replacement of fish meal and fish oil with terrestrial feed ingredients may further increase pressure on freshwater resources. At the same time economic consumptive water productivity may be reduced, especially for carnivorous species. The results of the present study show that, for the aquaculture sector to grow sustainably, freshwater consumption and pollution due to aquafeed need to be taken into account. PMID- 26258558 TI - The Combined Impact of Surgical Team Education and Chlorhexidine 2% Alcohol on the Reduction of Surgical Site Infection following Cardiac Surgery. AB - BACKGROUND: The use of 2% chlorhexidine in 70% alcohol (CHG) has been associated with reduction in catheter-related bloodstream infections and surgical site infection (SSI) in general surgery. Also, improved awareness of best practice from the perspective of the operative team is likely to result in reductions in SSI rates. METHODS: This is an ambispective cohort study of patients undergoing elective cardiac surgery. Between January 2010 and December 2010, patients underwent surgical preparation using Alcohol Povidone Iodine (API). Between January 2011 and December 2011, the surgical team received education and switched to CHG for surgical preparation. Univariate analysis was performed to identify the impact of known risk factors for SSI. A logistic regression model was then fit to estimate the effect of education and CHG in the reduction of SSI in 2011, controlling for known SSI risk factors. RESULTS: There was a substantial reduction in overall SSI rate in 2011 following staff education and the introduction of CHG. The overall unadjusted SSI rate was 4.67% versus 2.08% (p<0.05) for 2010 and 2011 respectively. Using a logistic regression model, the combined effect of education and CHG in 2011 was a 63% reduction in SSI in cardiothoracic surgery (OR 0.37, 95% CI: 0.17-0.83, p=0.016), controlling for age, major co-morbidities, and SSI risk factors. CONCLUSIONS: Using CHG as pre operative antiseptic in cardiothoracic surgery in a risk-adjusted cohort with education of the surgical team is associated with significantly lower SSI infection rates when compared with API. Emphasis must be placed on the multifactorial approach required to prevent postoperative wound infections. PMID- 26258559 TI - Combined oral administration of bovine collagen peptides with calcium citrate inhibits bone loss in ovariectomized rats. AB - PURPOSE: Collagen peptides (CPs) and calcium citrate are commonly used as bone health supplements for treating osteoporosis. However, it remains unknown whether the combination of oral bovine CPs with calcium citrate is more effective than administration of either agent alone. METHODS: Forty 12-week-old Sprague-Dawley rats were randomly divided into five groups (n = 8) for once-daily intragastric administration of different treatments for 3 months at 3 months after ovariectomy (OVX) as follows: sham + vehicle; OVX + vehicle; OVX + 750 mg/kg CP; OVX + CP calcium citrate (75 mg/kg); OVX + calcium citrate (75 mg/kg). After euthanasia, the femurs were removed and analyzed by dual energy X-ray absorptiometry and micro-computed tomography, and serum samples were analyzed for bone metabolic markers. RESULTS: OVX rats supplemented with CPs or CP-calcium citrate showed osteoprotective effects, with reductions in the OVX-induced decreases in their femoral bone mineral density. Moreover, CP-calcium citrate prevented trabecular bone loss, improved the microarchitecture of the distal femur, and significantly inhibited bone loss with increased bone volume, connectivity density, and trabecular number compared with OVX control rats. CP or CP-calcium citrate administration significantly increased serum procollagen type I N-terminal propeptide levels and reduced serum bone-specific alkaline phosphatase, osteocalcin, and C-telopeptide of type I collagen levels. CONCLUSIONS: Our data indicate that combined oral administration of bovine CPs with calcium citrate inhibits bone loss in OVX rats. The present findings suggest that combined oral administration of bovine CPs with calcium citrate is a promising alternative for reducing bone loss in osteopenic postmenopausal women. PMID- 26258560 TI - Sugar-Sweetened Beverages and Obesity among Children and Adolescents: A Review of Systematic Literature Reviews. AB - BACKGROUND: The prevalence of overweight and obesity among children and adolescents has increased worldwide and has reached alarming proportions. Currently, sugar-sweetened beverages (SSBs) are the primary source of added sugar in the diet of children and adolescents. Contradictive findings from studies and reviews have fueled an endless debate on the role of SSBs in the development of childhood obesity. OBJECTIVES: The primary aim of the present review of reviews was to assess how review- and study-level methodological factors explain conflicting results across reviews and meta-analyses by providing an up-to-date synthesis of recent evidence regarding the association between SSB consumption and weight gain, overweight, and obesity in a population of 6-month-old to 19 year-old children and adolescents. The secondary aim was to assess the quality of included reviews using the Assessment of Multiple SysTemAtic Reviews (AMSTAR) measurement tool. METHODS: Systematic literature reviews and meta-analyses were included. The literature search was performed through the platforms Pubmed/Medline, Cinahl, and Web of Knowledge. RESULTS: Thirteen reviews and meta analyses were included. Nine reviews concluded that there was a direct association between SSBs and obesity in children and adolescents and four others did not. The quality of the included reviews was low to moderate, and the two reviews with the highest quality scores showed discrepant results. CONCLUSIONS: The majority of reviews concluded that there was a direct association between SSB consumption and weight gain, overweight, and obesity in children and adolescents. However, recent evidence from well-conducted meta-analyses shows discrepant results regarding the association between SSB and weight gain, overweight, and obesity among children and adolescents. Improving methodological quality of studies and reviews as well as ensuring responsible conduct of research and scientific integrity is essential for the provision of objective results. PMID- 26258561 TI - The Role of Parenting Practices in the Home Environment among Underserved Youth. AB - BACKGROUND: The home environment, which includes parenting practices, is an important setting in which children develop their health behaviors. We examined the role of parenting practices in the home environment among underserved youth. METHODS: We examined baseline data of a family-focused pediatric obesity intervention. Parenting practices (monitoring, discipline, limit setting of soda/snacks [SS] and screen media [SM], pressure to eat, and reinforcement) and availability of fruits/vegetables (FV) and sugar-sweetened beverages (SSBs), family meals, television (TV) watching during meals, TVs in the home, owning active video games/sports equipment, and household food security were assessed in 301 parent/caregivers of overweight/obese children (ages 7-12 years; BMI>=85th percentile). Associations were evaluated using Spearman's rank correlation coefficients and logistic regression models adjusted for potential confounders. RESULTS: Parents/caregivers (ages 22-67 years) were largely Hispanic/Latino (74.1%), female (92.4%), and reported high levels of limit setting SS and low levels of pressure to eat. Parent age, gender, country of birth, and years living in the United States accounted for differences among several parenting practices. Adjusted logistic regression models identified several statistically significant associations, including: Monitoring was positively associated with availability FV (odds ratio [OR]=2.19; 95% confidence interval [CI], 1.25, 3.82); limit setting SS was inversely associated with availability of SSBs (OR=0.40; 95% CI, 0.21, 0.75); and limit setting SM was inversely associated with TV viewing during family meals (OR=0.51; 95% CI, 0.31, 0.85). Nearly 40% of our population was food insecure, and food insecurity was positively associated with pressure to eat (OR=1.77; 95% CI, 1.01, 3.15). CONCLUSIONS: Parenting practices play an important role in the home environment, and longitudinal studies are needed to examine these associations in the context of family-focused pediatric obesity interventions. PMID- 26258562 TI - The Relationship between Obesity and Cognitive Performance in Children: A Longitudinal Study. AB - BACKGROUND: The relationship between obesity and academic outcomes remains unclear. We evaluated the association between obesity and cognitive performance in US children. METHODS: We analyzed two nationally representative prospective cohorts of children in the 1979 National Longitudinal Survey of Youth, ages 2 through 8 at baseline and followed for 6 years, from 1988 to 1994 (cohort 1, n=2672) and 1994 to 2000 (cohort 2, n=1991). The main exposure variable was obesity (defined as never obese, became obese, always obese, and became nonobese). The main outcomes were standardized scores on four cognitive assessments. Univariate regression analyses of test scores on obesity were performed. Fixed-effects regression models, controlling for measured and unmeasured time-invariant confounders, were additionally adjusted for time variant confounders to analyze the impact of change in obesity status on change in test scores. RESULTS: Unadjusted analyses revealed a significant association between obesity and Peabody Individual Achievement Test (PIAT) scores. In cohort 1, always obese children had lower PIAT math scores than never obese children (beta=-7.48; p<0.05). Always obese boys had lower PIAT math scores than those who were never obese (beta=-16.45; p<0.01). In cohort 2, PIAT math scores were lower in the became obese category than the never obese category (beta=-4.10; p<0.05). Always obese girls had lower PIAT reading scores than those who were never obese (beta=-11.28; p<0.01). Fixed-effects models additionally adjusted for Home Observation Measurement of the Environment, Short Form score and height percentile showed no significant relationship between obesity and test scores in either cohort. CONCLUSION: Childhood obesity is unlikely to be causally related to cognitive performance. PMID- 26258563 TI - Observing Nucleation Transition in Stretched Natural Rubber through Self-Seeding. AB - Potential competition between fringed-micelle nucleation (N1) and folded-chain nucleation (N2) widely exists in strain-induced crystallization (SIC). However, during uniaxial deformation, no in situ observational evidence of nucleation transition from N2 to N1 in SIC of natural rubber (NR) has been reported yet. In this work, self-seeding provides an effective way for this observation. By the introduction of residual TIC (temperature-induced crystallization)-melting crystallites into pure NR system, in situ synchronic WAXD revealed the formation of low-oriented crystal in the initial deformation stage, which gradually evolves into highly oriented crystal at last. The low-oriented crystal is related to secondary folded-chain nucleation (N2) on the surface of residual TIC-melting crystallites (self-seeding), while newly formed highly oriented crystal is associated with N1. For the first time, the concept of "self-seeding" is innovatively applied to SIC process so that NR exhibits clear nucleation transition phenomenon. Further, theoretical computation of nucleation barrier in the special NR system well reflects that self-seeding has the role of both increasing critical strain of nucleation transition and decreasing onset strain of SIC, thus providing conditions for the observation. PMID- 26258564 TI - Implementation and Operational Research: Cost-Effectiveness of Antiretroviral Therapy and Isoniazid Prophylaxis to Reduce Tuberculosis and Death in People Living With HIV in Botswana. AB - OBJECTIVE: In Botswana, a 36-month course of isoniazid treatment of latent tuberculosis (TB) infection [isoniazid preventive therapy (IPT)] was superior to 6-month IPT in reducing TB and death in persons living with HIV (PLHIV), having positive tuberculin skin tests (TSTs) but not in those with negative TST. We examined the cost-effectiveness of IPT in Botswana, where antiretroviral therapy (ART) is widely available. DESIGN: Using a decision-analytic model, we determined the incremental cost-effectiveness of strategies for reducing TB and death in 10,000 PLHIV over 36 months. METHODS: IPT for 6 months and provision of ART if CD4 lymphocyte count <250 cells per microliter (2011 Botswana policy) was compared with 6 alternative strategies that varied the use of IPT, TST, and ART for CD4 count thresholds, including CD4 <350 and <500 cells per microliter. RESULTS: Botswana policy, 2011 was dominated by most other strategies. IPT of 36 months for TST-positive PLHIV with ART for CD4 <250 cells per microliter resulted in 120 fewer TB cases for an additional cost of $1612 per case averted and resulted in 80 fewer deaths for an additional $2418 per death averted compared with provision of 6-month IPT to TST-positive PLHIV who received ART for CD4 <250 cells per microliter, the next most effective strategy. Alternative strategies offered lower incremental effectiveness at higher cost. These findings remained consistent in sensitivity analyses. CONCLUSIONS: A strategy of treating PLHIV who have positive TST with 36-month IPT is more cost effective for reducing both TB and death compared with providing IPT without a TST, providing only 6-month IPT, or expanding ART eligibility without IPT. PMID- 26258566 TI - Association of Hippocampal Magnetic Resonance Imaging With Learning and Memory Deficits in HIV-1-Seropositive Patients. AB - OBJECTIVE: To investigate the relationship between cognitive impairment and hippocampal morphological and functional changes in HIV-seropositive patients. METHODS: Thirty HIV+ patients who complain of memory decrease and 15 healthy volunteers were recruited. Performances of learning and memory were assessed using Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R). Bilateral hippocampal volume, apparent diffusion coefficient (ADC) value, fractional anisotropy value, and magnetic resonance spectroscopy variables of bilateral hippocampus and parahippocampal gyrus were detected by 3.0 T magnetic resonance scanner. RESULTS: We found significant differences in all cognitive outcomes but one between HIV+ and HIV- patients. There was a difference in the ADC value of left parahippocampal gyrus between mild-impairment group and severe-impairment group (P = 0.018). We found differences in the choline (Cho), Cho/creatinine (Cr), and N-acetylaspartate/Cr of left hippocampus (P = 0.002, P = 0.008, P = 0.002) and the Cho/Cr of right parahippocampal gyrus (P = 0.023) between HIV+ and HIV- patients and in the myoinositol of left hippocampus (P = 0.003) and the glutamate and glutamine of right hippocampus (P < 0.001) between mild-impairment group and severe-impairment group. We found significant positive correlations between N-acetylaspartate/Cr of left hippocampus and outcomes of HVLT-R and BVMT-R. There were significant negative correlations between ADC values of hippocampus and parahippocampal gyrus and outcomes of HVLT-R and BVMT-R and between Cho and Cho/Cr of hippocampus and parahippocampal gyrus and outcomes of HVLT-R and BVMT-R. CONCLUSIONS: The performance of verbal learning and visual memory was significantly decreased in HIV-1-seropositive patients. The cognitive impairment of HIV infection was associated with conductive function and metabolic changes of hippocampus and parahippocampal gyrus in this study. PMID- 26258565 TI - Neuronal-Glia Markers by Magnetic Resonance Spectroscopy in HIV Before and After Combination Antiretroviral Therapy. AB - OBJECTIVE: Combination antiretroviral therapy (cART) can suppress plasma HIV RNA to undetectable levels; yet reports indicate persistent HIV-associated neurocognitive disorders (HAND) among treated individuals. We sought to investigate imaging correlates of incomplete cognitive recovery among individuals with chronic HIV. METHODS: We used single voxel proton magnetic resonance spectroscopy in 4 regions of the brain to measure changes in neuronal and glia biomarkers in cART-naive subjects before (n = 59, 27 with HAND) and after 12 months of cART. RESULTS: At baseline, we observed elevated total choline (CHO) in the basal ganglia (BG, P = 0.002) and in the posterior cingulate gyrus (PCG, P = 0.022) associated with HIV infection. Myo-inositol (MI) was elevated in the frontal white matter (FWM, P = 0.040). N-acetylaspartate was elevated in the BG (P = 0.047). Using a mixed model approach among all HIV-infected individuals, at 6 months, we observed decreased n- acetylaspartate in FWM (P = 0.031), decreased creatine in PCG (P = 0.026) and increased MI in frontal gray matter (FGM, P = 0.023). At 12 months, we observed an increase in BG MI (P = 0.038) and in FGM (P = 0.021). Compared to those with normal cognition, HAND cases had higher FGM MI (P = 0.014) at baseline. At 12 months, individuals that remained cognitively impaired compared with those without HAND exhibited elevated CHO in the PCG (P = 0.018) and decreased glutamate in both FWM (P = 0.027) and BG (P = 0.013). CONCLUSIONS: cART started during chronic HIV is associated with reduced neuronal glia and inflammatory markers. Alterations in CHO are noted among individuals who remain impaired after 12 months of cART. PMID- 26258568 TI - Phylogenetic Analysis of HIV-1 CRF65_CPX Reveals Yunnan Province Is Still a Source Contributing to the Spread of HIV-1 in China. PMID- 26258567 TI - Implementation and Operational Research: Strengthening HIV Test Access and Treatment Uptake Study (Project STATUS): A Randomized Trial of HIV Testing and Counseling Interventions. AB - OBJECTIVE: To determine which of 3 HIV testing and counseling (HTC) models in outpatient departments (OPDs) increases HIV testing and entry of newly identified HIV-infected patients into care. DESIGN: Randomized trial of HTC interventions. METHODS: Thirty-six OPDs in South Africa, Tanzania, and Uganda were randomly assigned to 3 different HTC models: (A) health care providers referred eligible patients (aged 18-49, not tested in the past year, not known HIV positive) to on site voluntary counseling and testing for HTC offered and provided by voluntary counseling and testing counselors after clinical consultation; (B) health care providers offered and provided HTC to eligible patients during clinical consultation; and (C) nurse or lay counselors offered and provided HTC to eligible patients before clinical consultation. Data were collected from October 2011 to September 2012. We describe testing eligibility and acceptance, HIV prevalence, and referral and entry into care. Chi-square analyses were conducted to examine differences by model. RESULTS: Of 79,910 patients, 45% were age eligible and 16,099 (45%) age eligibles were tested. Ten percent tested HIV positive. Significant differences were found in percent tested by model. The proportion of age eligible patients tested by Project STATUS was highest for model C (54.1%, 95% confidence interval [CI]: 42.4 to 65.9), followed by model A (41.7%, 95% CI: 30.7 to 52.8), and then model B (33.9%, 95% CI: 25.7 to 42.1). Of the 1596 newly identified HIV positive patients, 94% were referred to care (96.1% in model A, 94.7% in model B, and 94.9% in model C), and 58% entered on-site care (74.4% in model A, 54.8% in model B, and 55.6% in model C) with no significant differences in referrals or care entry by model. CONCLUSIONS: Model C resulted in the highest proportion of all age-eligible patients receiving a test. Although 94% of STATUS patients with a positive test result were referred to care, only 58% entered care. We found no differences in patients entering care by HTC model. Routine HTC in OPDs is acceptable to patients and effective for identifying HIV infected persons, but additional efforts are needed to increase entry to care. PMID- 26258569 TI - Phylogenetic Investigation of a Statewide HIV-1 Epidemic Reveals Ongoing and Active Transmission Networks Among Men Who Have Sex With Men. AB - BACKGROUND: Molecular epidemiological evaluation of HIV-1 transmission networks can elucidate behavioral components of transmission that can be targets for intervention. METHODS: We combined phylogenetic and statistical approaches using pol sequences from patients diagnosed between 2004 and 2011 at a large HIV center in Rhode Island, following 75% of the state's HIV population. Phylogenetic trees were constructed using maximum likelihood, and putative transmission clusters were evaluated using latent class analyses to determine association of cluster size with underlying demographic/behavioral characteristics. A logistic growth model was used to assess intracluster dynamics over time and predict "active" clusters that were more likely to harbor undiagnosed infections. RESULTS: Of the 1166 HIV-1 subtype B sequences, 31% were distributed among 114 statistically supported, monophyletic clusters (range: 2-15 sequences/cluster). Sequences from men who have sex with men (MSM) formed 52% of clusters. Latent class analyses demonstrated that sequences from recently diagnosed (2008-2011) MSM with primary HIV infection (PHI) and other sexually transmitted infections (STIs) were more likely to form larger clusters (odds ratio: 1.62-11.25, P < 0.01). MSM in clusters were more likely to have anonymous partners and meet partners at sex clubs and pornographic stores. Four large clusters with 38 sequences (100% male, 89% MSM) had a high probability of harboring undiagnosed infections and included younger MSM with PHI and STIs. CONCLUSIONS: In this first large-scale molecular epidemiological investigation of HIV-1 transmission in New England, sexual networks among recently diagnosed MSM with PHI and concomitant STIs contributed to the ongoing transmission. Characterization of transmission dynamics revealed actively growing clusters, which may be targets for intervention. PMID- 26258570 TI - Measuring the HIV Care Continuum Using Public Health Surveillance Data in the United States. AB - The HIV care continuum is a critical framework for situational awareness of the HIV epidemic; yet challenges to accurate enumeration of continuum components hamper continuum estimation in practice. We describe local surveillance-based estimation of the HIV continuum in the United States, reviewing common practices as recommended by the Centers for Disease Control and Prevention. Furthermore, we review some challenges and biases likely to threaten existing continuum estimates. Current estimates rely heavily on the use of CD4 cell count and HIV viral load laboratory results reported to surveillance programs as a proxy for receipt of HIV-related outpatient care. As such, continuum estimates are susceptible to bias because of incomplete laboratory reporting and imperfect sensitivity and specificity of laboratory tests as a proxy for routine HIV care. Migration of HIV-infected persons between jurisdictions also threatens the validity of continuum estimates. Data triangulation may improve but not fully alleviate biases. PMID- 26258571 TI - Reduced Levels of D-dimer and Changes in Gut Microbiota Composition After Probiotic Intervention in HIV-Infected Individuals on Stable ART. AB - BACKGROUND: Microbial translocation and chronic inflammation may contribute to non-AIDS morbidity in patients with HIV. This study assessed the impact of probiotic intervention on microbial translocation and inflammation in patients on antiretroviral therapy with viral suppression and subnormal CD4 count. METHODS: Thirty-two patients receiving antiretroviral therapy (CD4 <500 cells/MUL) were randomized in a double-blind fashion to multistrain daily probiotics (n = 15), placebo (n = 9), or controls (n = 8) for 8 weeks. Soluble inflammation markers, D dimer, lipopolysaccharide (LPS), sCD14, T-cell activation, tryptophan metabolites, and gut microbiota composition were analyzed at baseline and end of study. Nonparametric statistics were applied. RESULTS: Twenty-four participants completed the study and were included in as-treated analyses. In patients receiving probiotics, there was a significant reduction in D-dimer levels (median change 33%, P = 0.03) and a tendency to reduced levels of C-reactive protein (CRP) (P = 0.05) and interleukin (IL)-6 (P = 0.06). The changes in CRP and IL-6 were highly correlated (r = 0.95, P < 0.01), whereas changes in D-dimer did not correlate with changes in CRP or IL-6. Increases in Bifidobacteria (P = 0.04) and Lactobacilli (P = 0.06) were observed in the probiotic group, whereas the relative abundance of Bacteroides decreased (P <= 0.01). No significant changes were seen in markers of microbial translocation or T-cell activation. However, the expansion of Bifidobacteria correlated negatively with differences in LPS (r = -0.77, P = 0.01), whereas the reduction in Bacteroides correlated positively with changes in LPS during the study period (r = 0.72, P = 0.02). CONCLUSIONS: Probiotic intervention seemed to reduce markers of coagulation and inflammation without overt changes in microbial translocation. These findings warrant further studies in larger cohorts with long-term follow-up. PMID- 26258572 TI - Brief Report: HIV Prevention by Australian Gay and Bisexual Men With Casual Partners: The Emergence of Undetectable Viral Load as One of a Range of Risk Reduction Strategies. AB - We analyzed the HIV risk reduction strategies (RRS) used by Australian gay and bisexual men with casual partners. Among 1346 men who reported any condomless anal intercourse with casual partners, 75% frequently practiced at least one RRS. The most common RRS was serosorting, frequently practiced by 55% of HIV-positive and 47% of HIV-negative participants. Condoms were frequently (but inconsistently) used by 17% of HIV-positive, 41% of HIV-negative, and 30% of untested participants. Relying on an undetectable viral load was frequently practiced by 58% of HIV-positive participants. Strategic positioning, withdrawal, and non-HIV-positive men taking antiretroviral medication were less common strategies. PMID- 26258573 TI - Genome-Wide Analysis of Oleosin Gene Family in 22 Tree Species: An Accelerator for Metabolic Engineering of BioFuel Crops and Agrigenomics Industrial Applications? AB - Trees contribute to enormous plant oil reserves because many trees contain 50% 80% of oil (triacylglycerols, TAGs) in the fruits and kernels. TAGs accumulate in subcellular structures called oil bodies/droplets, in which TAGs are covered by low-molecular-mass hydrophobic proteins called oleosins (OLEs). The OLEs/TAGs ratio determines the size and shape of intracellular oil bodies. There is a lack of comprehensive sequence analysis and structural information of OLEs among diverse trees. The objectives of this study were to identify OLEs from 22 tree species (e.g., tung tree, tea-oil tree, castor bean), perform genome-wide analysis of OLEs, classify OLEs, identify conserved sequence motifs and amino acid residues, and predict secondary and three-dimensional structures in tree OLEs and OLE subfamilies. Data mining identified 65 OLEs with perfect conservation of the "proline knot" motif (PX5SPX3P) from 19 trees. These OLEs contained >40% hydrophobic amino acid residues. They displayed similar properties and amino acid composition. Genome-wide phylogenetic analysis and multiple sequence alignment demonstrated that these proteins could be classified into five OLE subfamilies. There were distinct patterns of sequence conservation among the OLE subfamilies and within individual tree species. Computational modeling indicated that OLEs were composed of at least three alpha-helixes connected with short coils without any beta-strand and that they exhibited distinct 3D structures and ligand binding sites. These analyses provide fundamental information in the similarity and specificity of diverse OLE isoforms within the same subfamily and among the different species, which should facilitate studying the structure-function relationship and identify critical amino acid residues in OLEs for metabolic engineering of tree TAGs. PMID- 26258574 TI - Phase Tuning of Nanostructured Gallium Oxide via Hybridization with Reduced Graphene Oxide for Superior Anode Performance in Li-Ion Battery: An Experimental and Theoretical Study. AB - The crystal phase of nanostructured metal oxide can be effectively controlled by the hybridization of gallium oxide with reduced graphene oxide (rGO) at variable concentrations. The change of the ratio of Ga2O3/rGO is quite effective in tailoring the crystal structure and morphology of nanostructured gallium oxide hybridized with rGO. This is the first example of the phase control of metal oxide through a change of the content of rGO hybridized. The calculations based on density functional theory (DFT) clearly demonstrate that the different surface formation energy and Ga local symmetry of Ga2O3 phases are responsible for the phase transition induced by the change of rGO content. The resulting Ga2O3-rGO nanocomposites show promising electrode performance for lithium ion batteries. The intermediate Li-Ga alloy phases formed during the electrochemical cycling are identified with the DFT calculations. Among the present Ga2O3-rGO nanocomposites, the material with mixed alpha-Ga2O3/beta-Ga2O3/gamma-Ga2O3 phase can deliver the largest discharge capacity with the best cyclability and rate characteristics, highlighting the importance of the control of Ga2O3/rGO ratio in optimizing the electrode activity of the composite materials. The present study underscores the usefulness of the phase-control of nanostructured metal oxides achieved by the change of rGO content in exploring novel functional nanocomposite materials. PMID- 26258575 TI - Fast, Continuous Audiogram Estimation Using Machine Learning. AB - OBJECTIVES: Pure-tone audiometry has been a staple of hearing assessments for decades. Many different procedures have been proposed for measuring thresholds with pure tones by systematically manipulating intensity one frequency at a time until a discrete threshold function is determined. The authors have developed a novel nonparametric approach for estimating a continuous threshold audiogram using Bayesian estimation and machine learning classification. The objective of this study was to assess the accuracy and reliability of this new method relative to a commonly used threshold measurement technique. DESIGN: The authors performed air conduction pure-tone audiometry on 21 participants between the ages of 18 and 90 years with varying degrees of hearing ability. Two repetitions of automated machine learning audiogram estimation and one repetition of conventional modified Hughson-Westlake ascending-descending audiogram estimation were acquired by an audiologist. The estimated hearing thresholds of these two techniques were compared at standard audiogram frequencies (i.e., 0.25, 0.5, 1, 2, 4, 8 kHz). RESULTS: The two threshold estimate methods delivered very similar estimates at standard audiogram frequencies. Specifically, the mean absolute difference between estimates was 4.16 +/- 3.76 dB HL. The mean absolute difference between repeated measurements of the new machine learning procedure was 4.51 +/- 4.45 dB HL. These values compare favorably with those of other threshold audiogram estimation procedures. Furthermore, the machine learning method generated threshold estimates from significantly fewer samples than the modified Hughson Westlake procedure while returning a continuous threshold estimate as a function of frequency. CONCLUSIONS: The new machine learning audiogram estimation technique produces continuous threshold audiogram estimates accurately, reliably, and efficiently, making it a strong candidate for widespread application in clinical and research audiometry. PMID- 26258577 TI - First-Principles Study of Ion Diffusion in Perovskite Solar Cell Sensitizers. AB - Hysteresis in current-voltage curves has been an important issue for conversion efficiency evaluation and development of perovskite solar cells (PSCs). In this study, we explored the ion diffusion effects in tetragonal CH3NH3PbI3 (MAPbI3) and trigonal (NH2)2CHPbI3 (FAPbI3) by first-principles calculations. The calculated activation energies of the anionic and cationic vacancy migrations clearly show that I(-) anions in both MAPbI3 and FAPbI3 can easily diffuse with low barriers of ca. 0.45 eV, comparable to that observed in ion-conducting materials. More interestingly, typical MA(+) cations and larger FA(+) cations both have rather low barriers as well, indicating that the cation molecules can migrate in the perovskite sensitizers when a bias voltage is applied. These results can explain the ion displacement scenario recently proposed by experiments. With the dilute diffusion theory, we discuss that smaller vacancy concentrations (higher crystallinity) and replacement of MA(+) with larger cation molecules will be essential for suppressing hysteresis as well as preventing aging behavior of PSC photosensitizers. PMID- 26258576 TI - Transcriptomics Analysis of Crassostrea hongkongensis for the Discovery of Reproduction-Related Genes. AB - BACKGROUND: The reproductive mechanisms of mollusk species have been interesting targets in biological research because of the diverse reproductive strategies observed in this phylum. These species have also been studied for the development of fishery technologies in molluscan aquaculture. Although the molecular mechanisms underlying the reproductive process have been well studied in animal models, the relevant information from mollusks remains limited, particularly in species of great commercial interest. Crassostrea hongkongensis is the dominant oyster species that is distributed along the coast of the South China Sea and little genomic information on this species is available. Currently, high throughput sequencing techniques have been widely used for investigating the basis of physiological processes and facilitating the establishment of adequate genetic selection programs. RESULTS: The C.hongkongensis transcriptome included a total of 1,595,855 reads, which were generated by 454 sequencing and were assembled into 41,472 contigs using de novo methods. Contigs were clustered into 33,920 isotigs and further grouped into 22,829 isogroups. Approximately 77.6% of the isogroups were successfully annotated by the Nr database. More than 1,910 genes were identified as being related to reproduction. Some key genes involved in germline development, sex determination and differentiation were identified for the first time in C.hongkongensis (nanos, piwi, ATRX, FoxL2, beta-catenin, etc.). Gene expression analysis indicated that vasa, nanos, piwi, ATRX, FoxL2, beta-catenin and SRD5A1 were highly or specifically expressed in C.hongkongensis gonads. Additionally, 94,056 single nucleotide polymorphisms (SNPs) and 1,699 simple sequence repeats (SSRs) were compiled. CONCLUSIONS: Our study significantly increased C.hongkongensis genomic information based on transcriptomics analysis. The group of reproduction-related genes identified in the present study constitutes a new tool for research on bivalve reproduction processes. The large group of molecular markers discovered in this study will be useful for population screening and marker assisted selection programs in C.hongkongensis aquaculture. PMID- 26258578 TI - State variations in women's socioeconomic status and use of modern contraceptives in Nigeria. AB - BACKGROUND: According to the 2014 World Population Data Sheet, Nigeria has one of the highest fertility and lowest contraceptive prevalence rates around the world. However, research suggests that national contraceptive prevalence rate overshadows enormous spatial variations in reproductive behavior in the country. OBJECTIVE: I examined the variations in women's socioeconomic status and modern contraceptive use across states in Nigeria. METHODS: Using the 2013 Nigeria Demographic and Health Survey data (n = 18,910), I estimated the odds of modern contraceptive use among sexually active married and cohabiting women in a series of multilevel logistic regression models. RESULTS: The share of sexually active, married and cohabiting women using modern contraceptives widely varied, from less than one percent in Kano, Yobe, and Jigawa states, to 40 percent in Osun state. Most of the states with low contraceptive prevalence rates also ranked low on women's socioeconomic attributes. Results of multilevel logistic regression analyses showed that women residing in states with greater shares of women with secondary or higher education, higher female labor force participation rates, and more women with health care decision-making power, had significantly higher odds of using modern contraceptives. Differences in women's participation in health care decisions across states remained significantly associated with modern contraceptive use, net of individual-level socioeconomic status and other covariates of modern contraceptive use. CONCLUSION: Understanding of state variations in contraceptive use is crucial to the design and implementation of family planning programs. The findings reinforce the need for state-specific family planning programs in Nigeria. PMID- 26258579 TI - Stretch-Triggered Drug Delivery from Wearable Elastomer Films Containing Therapeutic Depots. AB - Mechanical force-based stimulus provides a simple and easily accessible manner for spatiotemporally controlled drug delivery. Here we describe a wearable, tensile strain-triggered drug delivery device consisting of a stretchable elastomer and microgel depots containing drug loaded nanoparticles. By applying a tensile strain to the elastomer film, the release of drug from the microdepot is promoted due to the enlarged surface area for diffusion and Poisson's ratio induced compression on the microdepot. Correspondingly, both sustained drug release by daily body motions and pulsatile release by intentional administration can be conveniently achieved. Our work demonstrated that the tensile strain, applied to the stretchable device, facilitated release of therapeutics from microdepots for anticancer and antibacterial treatments. Moreover, polymeric microneedles were further integrated with the stretch-responsive device for transcutaneous delivery of insulin and regulation of blood glucose levels of chemically induced type 1 diabetic mice. PMID- 26258580 TI - Production and characterization of novel self-assembling biosurfactants from Aspergillus flavus. AB - AIM: This work was conducted to produce, purify and characterize biosurfactants from Aspergillus flavus AF612 isolated from citrus fruit. METHODS AND RESULTS: Biosurfactant named 'Uzmaq' was isolated from A. flavus AF612. The chemical characterization of the biosurfactant was conducted. Biosurfactant Uzmaq produced by A. flavus, was composed of methoxy phenyl oxime glycosides. Two molecular forms of the biosurfactant, Uzmaq-A and Uzmaq-B were isolated. Biological properties (antifungal activity) were evaluated. The fractions of the biosurfactant were isolated and their surface properties were analysed. Uzmaq-A and Uzmaq-B had critical micelle concentration (CMC) around 170 and 80 mg l(-1) , and lowered surface tension of water up to 20 and 25 m Nm(-1) respectively. The biosurfactants were stable at pH 3-12 and temperature up to 80 degrees C. Growth and biosurfactant production kinetics were also analysed. CONCLUSION: Novel biosurfactant Uzmaq was produced from A. flavus, which was composed of methoxy phenyl oxime glycosides. The surface activity of Uzmaq was better than the maximum values of synthetic chemical surfactants. The biosurfactant showed antifungal activity and self-assembling properties. SIGNIFICANCE AND IMPACT OF THE STUDY: Aspergillus flavus AF612 can be used for commercial production of Uzmaq that may be employed for controlled drug release applications and bioremediation. PMID- 26258582 TI - In brief. Abdominal adhesions. PMID- 26258583 TI - Intra-abdominal adhesions: Anatomy, physiology, pathophysiology, and treatment. PMID- 26258584 TI - Two Reviews on Immune Dysfunction. PMID- 26258586 TI - Treatment of Skin Calcifications with Intra-lesional Injection of Sodium Thiosulphate: A Case Series. PMID- 26258587 TI - Procedures for the quantification of whole-tissue immunofluorescence images obtained at single-cell resolution during murine tubular organ development. AB - Whole-tissue quantification at single-cell resolution has become an inevitable approach for further quantitative understanding of morphogenesis in organ development. The feasibility of the approach has been dramatically increased by recent technological improvements in optical tissue clearing and microscopy. However, the series of procedures required for this approach to lead to successful whole-tissue quantification is far from developed. To provide the appropriate procedure, we here show tips for each critical step of the entire process, including fixation for immunofluorescence, optical clearing, and digital image processing, using developing murine internal organs such as epididymis, kidney, and lung as an example. Through comparison of fixative solutions and of clearing methods, we found optimal conditions to achieve clearer deep-tissue imaging of specific immunolabeled targets and explain what methods result in vivid volume imaging. In addition, we demonstrated that three-dimensional digital image processing after optical clearing produces objective quantitative data for the whole-tissue analysis, focusing on the spatial distribution of mitotic cells in the epididymal tubule. The procedure for the whole-tissue quantification shown in this article should contribute to systematic measurements of cellular processes in developing organs, accelerating the further understanding of morphogenesis at the single cell level. PMID- 26258588 TI - Detection of hepatitis B virus DNA with a paper electrochemical sensor. AB - Here we show that a simple paper-based electrochemical sensor, fabricated by paper folding, is able to detect a 30-base nucleotide sequence characteristic of DNA from the hepatitis B virus (HBV) with a detection limit of 85 pM. This device is based on design principles we have reported previously for detecting proteins via a metalloimmunoassay. It has four desirable attributes. First, its design combines simple origami (paper folding) assembly, the open structure of a hollow channel paper analytical device to accommodate micrometer-scale particles, and a convenient slip layer for timing incubation steps. Second, two stages of amplification are achieved: silver nanoparticle labels provide a maximum amplification factor of 250 000 and magnetic microbeads, which are mobile solid phase supports for the capture probes, are concentrated at a detection electrode and provide an additional ~25-fold amplification. Third, there are no enzymes or antibodies used in the assay, thereby increasing its speed, stability, and robustness. Fourth, only a single sample incubation step is required before detection is initiated. PMID- 26258589 TI - Mice undergoing neuropathic pain induce anxiogenic-like effects and hypernociception in cagemates. AB - Rodents can recognize pain-related responses in conspecifics. Therefore, cohabitation with a conspecific animal with chronic pain can potentially promote a stressful situation, which can trigger behavioral changes such as anxiety and depression and alter nociceptive responses. In this study we investigated the effect of cohabitation with a mouse undergoing sciatic nerve constriction (neuropathic pain model). The cagemates were evaluated for nociception (writhing test), anxiety (elevated plus-maze and open field tests), depression (forced swim, tail suspension, and sucrose preference tests), and corticosterone levels. Male Swiss mice were housed in pairs for 14 days, and then divided into three groups: cagemate nerve constriction, in which one animal of each pair was subjected to constriction of the sciatic nerve; cagemate sham, in which one animal from each pair was subjected to the same surgery but without constriction; and control, in which animals were not subjected to any surgical procedure. After 14 days, the cagemates were evaluated using behavioral tests. Social interaction with a conspecific undergoing constriction of the sciatic nerve induced hypernociception and increased anxiety-related responses, whereas in depression tests inconclusive responses and no changes in corticosterone levels were found. In conclusion, cohabitation with suffering conspecifics induces changes in nociceptive responses, as well as in affective responses including anxiety. PMID- 26258590 TI - Wetland suitability and connectivity for trans-Saharan migratory waterbirds. AB - To complete their life cycle waterbirds rely on patchily distributed and often ephemeral wetlands along their migration route in a vast unsuitable matrix. However, further loss and degradation of remaining wetland habitats might lead to a configuration and size of stopovers that is no longer sufficient to ensure long term survival of waterbird populations. By identifying optimal conservation targets to maintain overall habitat availability en route, we can accommodate an as yet absent functional connectivity component in larger management frameworks for migratory waterbirds, such as the Ramsar Convention and the EU Natura 2000 Network. Using a graph-based habitat availability metric (Equivalent Connected Area) we determine the functional connectivity of wetland networks for seven migratory waterbirds with divergent habitat requirements. Analyses are performed at two spatial extents both spanning the Mediterranean Sea and centered around Greece (Balkan-Cyrenaica and Greece-Cyrenaica). We create species-specific suitable habitat maps and account for human disturbance by species-specific disturbance buffers, based on expert estimates of Flight Initiation Distances. At both spatial extents we quantitatively determine the habitat networks' overall functional connectivity and identify wetland sites that are crucial for maintaining a well-connected network. We show that the wetland networks for both spatial extents are relatively well connected and identify several wetland sites in Greece and Libya as important for maintaining connectivity. The application of disturbance buffers results in wetland site-specific reduction of suitable habitat area (0.90-7.36%) and an overall decrease of the network's connectivity (0.65-6.82%). In addition, we show that the habitat networks of a limited set of species can be combined into a single network which accounts for their autoecological requirements. We conclude that targeted management in few but specific wetland complexes could benefit migratory waterbird populations. Deterioration of these vital wetland sites in Greece and Libya will have disproportionate consequences to the waterbird populations they support. PMID- 26258591 TI - miR-512-5p suppresses tumor growth by targeting hTERT in telomerase positive head and neck squamous cell carcinoma in vitro and in vivo. AB - Telomerase activation has very important implications for head and neck squamous cell carcinoma (HNSCC), but the regulatory mechanisms of telomerase in HNSCC remain unclear. In our present study, we found that miR-512-5P was markedly downregulated in telomerase-positive HNSCC cell lines. Both in vitro and in vivo assays revealed that miR-512-5P mimic attenuated HNSCC cell proliferation, and tumor growth in nude mice, which exerts its tumor suppressor function through elevated apoptosis, inhibition of the telomerase activity, decrease of telomere binding proteins and shortening of telomere length by human telomerase reverse transcriptase (hTERT) downregulation. Furthermore, the dual-luciferase reporter gene assay results demonstrated that hTERT was a direct target of miR-512-5P. We conclude that the frequently miR-512-5P overexpression can regulate hTERT and function as a tumor suppressor in HNSCC. Therefore, miR-512-5P may serve as a potential therapeutic agent for miR-based HNSCC therapy. PMID- 26258592 TI - Death from Nitrous Oxide. AB - Nitrous oxide is an inflammable gas that gives no smell or taste. It has a history of abuse as long as its clinical use, and deaths, although rare, have been reported. We describe two cases of accidental deaths related to voluntary inhalation of nitrous oxide, both found dead with a gas mask covering the face. In an attempt to find an explanation to why the victims did not react properly to oncoming hypoxia, we performed experiments where a test person was allowed to breath in a closed system, with or without nitrous oxide added. Vital signs and gas concentrations as well as subjective symptoms were recorded. The experiments indicated that the explanation to the fact that neither of the descendents had reacted to oncoming hypoxia and hypercapnia was due to the inhalation of nitrous oxide. This study raises the question whether nitrous oxide really should be easily, commercially available. PMID- 26258593 TI - Hysteretic Spin Crossover in Two-Dimensional (2D) Hofmann-Type Coordination Polymers. AB - Three new two-dimensional (2D) Hofmann-type coordination polymers with general formula [Fe(3-NH2py)2M(CN)4] (3-NH2py = 3-aminopyridine, M = Ni (1), Pd (2), Pt (3)) have been synthesized. Magnetic susceptibility measurements show that they exhibited cooperative spin crossover (SCO) with remarkable hysteretic behaviors. Their hysteresis widths are 25, 37, and 30 K for 1-3, respectively. The single crystal structure of 1 suggest that the pseudo-octahedral Fe sites are equatorially bridged by [M(CN)4](2-) to form 2D grids and axially coordinated by 3-NH2py ligands. The intermolecular interactions between layers (the offset face to-face pi...pi interactions, hydrogen bonds, and weak N(amino)...Ni(II) contacts) together with the covalent bonds bridged by [M(CN)4](2-) units are responsible to the significant cooperativity. PMID- 26258594 TI - Direct oriented growth of armchair graphene nanoribbons on germanium. AB - Graphene can be transformed from a semimetal into a semiconductor if it is confined into nanoribbons narrower than 10 nm with controlled crystallographic orientation and well-defined armchair edges. However, the scalable synthesis of nanoribbons with this precision directly on insulating or semiconducting substrates has not been possible. Here we demonstrate the synthesis of graphene nanoribbons on Ge(001) via chemical vapour deposition. The nanoribbons are self aligning 3 degrees from the Ge<110> directions, are self-defining with predominantly smooth armchair edges, and have tunable width to <10 nm and aspect ratio to >70. In order to realize highly anisotropic ribbons, it is critical to operate in a regime in which the growth rate in the width direction is especially slow, <5 nm h(-1). This directional and anisotropic growth enables nanoribbon fabrication directly on conventional semiconductor wafer platforms and, therefore, promises to allow the integration of nanoribbons into future hybrid integrated circuits. PMID- 26258595 TI - Insights into the molecular mechanisms of action of bioportides: a strategy to target protein-protein interactions. AB - Cell-penetrating peptides (CPPs) are reliable vehicles for the target-selective intracellular delivery of therapeutic agents. The identification and application of numerous intrinsically bioactive CPPs, now designated as bioportides, is further endorsement of the tremendous clinical potential of CPP technologies. The refinement of proteomimetic bioportides, particularly sequences that mimic cationic alpha-helical domains involved in protein-protein interactions (PPIs), provides tremendous opportunities to modulate this emergent drug modality in a clinical setting. Thus, a number of CPP-based constructs are currently undergoing clinical trials as human therapeutics, with a particular focus upon anti-cancer agents. A well-characterised array of synthetic modifications, compatible with modern solid-phase synthesis, can be utilised to improve the biophysical and pharmacological properties of bioportides and so achieve cell-and tissue selective targeting in vivo. Moreover, considering the recent successful development of stapled alpha-helical peptides as anti-cancer agents, we hypothesise that similar structural modifications are applicable to the design of bioportides that more effectively modulate the many interactomes known to underlie human diseases. Thus, we propose that stapled-helical bioportides could satisfy all of the clinical requirements for metabolically stable, intrinsically cell-permeable agents capable of regulating discrete PPIs by a dominant negative mode of action with minimal toxicity. PMID- 26258596 TI - One-Pot Domino Aldol Reaction of Indium Enolates Affording 6-Deoxy-alpha-D,L altropyranose Derivatives: Synthesis, Mechanism, and Computational Results. AB - The domino-aldol-aldol-hemiacetal-reaction cascade of indium and other group 13 metal enolates furnished 6-deoxy-alpha-D,L-altropyranose derivatives in up to 99% yield under thermodynamic control. At lower temperature and thus under kinetic control, the reaction proceeded in a much less diastereoselective manner. The changeover from kinetic to thermodynamic control operating in this multistep domino-aldol-aldol-hemiacetal protocol was used for probing the efficiency of DFT computations. Calculations at the B3LYP/6-31G(d)/LANL2DZ level provided a mechanistic picture in full agreement with the experimental outcome. PMID- 26258598 TI - The Pseudocavitation Sign of Lung Adenocarcinoma: A Distinguishing Feature and Imaging Biomarker of Lepidic Growth. AB - PURPOSE: Our purpose was to evaluate whether pseudocavitation, characterized by round or oval areas of low attenuation in a lesion on computed tomography (CT), can help distinguish adenocarcinoma from other types of non-small cell lung cancer (NSCLC). We also sought to determine whether pseudocavitation is associated with lepidic growth on histopathology. MATERIALS AND METHODS: This retrospective HIPAA-compliant study was approved by our institutional review board. The need for informed consent was waived. CT scans and pathology records from 158 NSCLCs in 149 patients were retrospectively reviewed. The frequency of pseudocavitation was compared among types of NSCLC, specifically adenocarcinoma versus other types of NSCLC. Subgroup analysis of adenocarcinomas was performed to identify any difference in the frequency of pseudocavitation between adenocarcinomas with reported lepidic growth and those without lepidic growth. RESULTS: There was a significantly greater frequency of pseudocavitation in adenocarcinomas versus other types of NSCLC [19/86 (22.1%) vs. 4/72 (5.6%), P=0.007]. The sensitivity and specificity of the pseudocavitation sign for adenocarcinoma were 0.22 and 0.94, respectively. Among adenocarcinomas, the pseudocavitation sign was more frequent in tumors with lepidic growth versus those without lepidic growth [10/24 (41.7%) vs. 9/62 (14.5%), P=0.015]. CONCLUSIONS: Pseudocavitation at CT is more common in primary lung adenocarcinoma than in other types of NSCLC. It is also more common in adenocarcinomas with lepidic growth, suggesting a correlation between the imaging finding of pseudocavitation and the pathologic finding of lepidic growth. As the subtype of NSCLC guides treatment, predicting tumor pathology by imaging may improve diagnostic workup for patients with NSCLC. PMID- 26258597 TI - High Intensity Interval Training Improves Glycaemic Control and Pancreatic beta Cell Function of Type 2 Diabetes Patients. AB - Physical activity improves the regulation of glucose homeostasis in both type 2 diabetes (T2D) patients and healthy individuals, but the effect on pancreatic beta cell function is unknown. We investigated glycaemic control, pancreatic function and total fat mass before and after 8 weeks of low volume high intensity interval training (HIIT) on cycle ergometer in T2D patients and matched healthy control individuals. Study design/method: Elderly (56 yrs+/-2), non-active T2D patients (n = 10) and matched (52 yrs+/-2) healthy controls (CON) (n = 13) exercised 3 times (10*60 sec. HIIT) a week over an 8 week period on a cycle ergometer. Participants underwent a 2-hour oral glucose tolerance test (OGTT). On a separate day, resting blood pressure measurement was conducted followed by an incremental maximal oxygen uptake (VO2max) cycle ergometer test. Finally, a whole body dual X-ray absorptiometry (DXA) was performed. After 8 weeks of training, the same measurements were performed. Results: in the T2D-group, glycaemic control as determined by average fasting venous glucose concentration (p = 0.01), end point 2-hour OGTT (p = 0.04) and glycosylated haemoglobin (p = 0.04) were significantly reduced. Pancreatic homeostasis as determined by homeostatic model assessment of insulin resistance (HOMA-IR) and HOMA beta cell function (HOMA %beta) were both significantly ameliorated (p = 0.03 and p = 0.03, respectively). Whole body insulin sensitivity as determined by the disposition index (DI) was significantly increased (p = 0.03). During OGTT, the glucose continuum was significantly reduced at -15 (p = 0.03), 30 (p = 0.03) and 120 min (p = 0.03) and at -10 (p = 0.003) and 0 min (p = 0.003) with an additional improvement (p = 0.03) of its 1st phase (30 min) area under curve (AUC). Significant abdominal fat mass losses were seen in both groups (T2D: p = 0.004 and CON: p = 0.02) corresponding to a percentage change of -17.84%+/-5.02 and -9.66%+/-3.07, respectively. Conclusion: these results demonstrate that HIIT improves overall glycaemic control and pancreatic beta cell function in T2D patients. Additionally, both groups experienced abdominal fat mass losses. These findings demonstrate that HIIT is a health beneficial exercise strategy in T2D patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02333734 http://clinicaltrials.gov/ct2/show/NCT02333734. PMID- 26258599 TI - Optimization of Radiology Reports for Intensive Care Unit Portable Chest Radiographs: Perceptions and Preferences of Radiologists and ICU Practitioners. AB - PURPOSE: The aim of the study was to evaluate opinions and perceptions of radiologists and referring practitioners regarding reports of portable chest radiography (pCXR) obtained in the intensive care unit (ICU). MATERIALS AND METHODS: A total of 1265 referring practitioners and 76 radiologists were invited to participate in 2 internet-based surveys, containing 15 and 17 multiple choice questions, respectively, similarly presented to both groups, utilizing a Likert scale or multiple choices. Results were compared using the Fisher exact test or chi test. RESULTS: One hundred ninety-two referring practitioners and 63 radiologists answered the surveys, resulting in response rates of 15% and 83%. The majority of radiologists and referring practitioners are satisfied with the quality of the reports; however, radiologists and referring practitioners disagree about the reports' clinical value and impact, the referring practitioners having a more positive view. Both groups overwhelmingly agree that pertinent clinical information is crucial for optimal image interpretation. The 2 groups differ in their preferences regarding report style and information content, with radiologists strongly supporting concise reports emphasizing temporal changes and major findings, whereas referring practitioners prefer more complete, itemized structured reports describing support devices in detail. CONCLUSIONS: The results substantiate the perceived clinical value of radiologist reports for pCXR, from the perspective of referring practitioners. Nonetheless, there is disagreement regarding report structure and content. Several issues were raised, offering opportunities for improvement, which may increase referring practitioners' satisfaction and positively impact patient outcomes. Any strategy to implement standardized structured reports for pCXR will have to satisfy referring practitioners' needs while optimizing radiologists' efficiency, will have to be widely accepted, and will have to fulfill the overarching goal of maximizing the value of pCXR reports. PMID- 26258600 TI - Imaging in Minimally Invasive Mitral Valve Repair. AB - Minimally invasive mitral valve (MV) repair and replacement techniques have evolved as increasingly used alternatives to open heart surgery especially in patients unsuitable for surgery or at high perioperative risk. The vast majority of these techniques are still under development, and only a limited number of devices are approved for clinical use; however, they do show promising results in terms of minimizing complications and improving clinical outcome. The complex anatomy of the MV and the annulus complicates not only the development of devices for minimally invasive MV repair or replacement but also complicates preprocedural planning, which is mandatory for minimization of postprocedural complications. Although echocardiography still plays a crucial clinical role, cross-sectional imaging modalities such as coronary computed tomography (CCT) and cardiac magnetic resonance imaging (CMR) are increasingly gaining importance for preprocedural planning. Specifically, CCT seems to be more practicable for preinterventional planning and device sizing, whereas CMR has been shown useful in detecting increased risk for adverse clinical outcomes through delayed gadolinium enhancement and the monitoring of cardiac morphology and function in the framework of follow-up examinations. This article describes recent techniques currently available or under development for minimally invasive repair or replacement of the MV and reviews the current state of CCT and CMR imaging for preinterventional and postinterventional diagnostic workup. PMID- 26258601 TI - Preprocedural Computed Tomography Evaluation for Minimally Invasive Mitral Valve Surgery: What the Surgeon Needs to Know. AB - The proven success of endoscopic and videoscopic surgery combined with recent advancements in telemanipulation has made the performance of minimally invasive cardiac surgery a clinical reality during the past decade. A complete understanding of the basic concepts of minimally invasive surgery and the recent advancements in peripheral cardiopulmonary bypass techniques help the cardiac imager to provide a clinically meaningful interpretation for the surgical team. In this article we present an overview of minimally invasive mitral valve surgery and the fundamentals of preprocedural computed tomography angiography imaging and highlight the usefulness of cardiac computed tomography as a supplementary tool to echocardiography. PMID- 26258602 TI - Discovery of Selective Small Molecule Inhibitors of Monoacylglycerol Acyltransferase 3. AB - Inhibition of triacylglycerol (TAG) biosynthetic enzymes has been suggested as a promising strategy to treat insulin resistance, diabetes, dyslipidemia, and hepatic steatosis. Monoacylglycerol acyltransferase 3 (MGAT3) is an integral membrane enzyme that catalyzes the acylation of both monoacylglycerol (MAG) and diacylglycerol (DAG) to generate DAG and TAG, respectively. Herein, we report the discovery and characterization of the first selective small molecule inhibitors of MGAT3. Isoindoline-5-sulfonamide (6f, PF-06471553) selectively inhibits MGAT3 with high in vitro potency and cell efficacy. Because the gene encoding MGAT3 (MOGAT3) is found only in higher mammals and humans, but not in rodents, a transgenic mouse model expressing the complete human MOGAT3 was used to characterize the effects of 6f in vivo. In the presence of a combination of diacylglycerol acyltransferases 1 and 2 (DGAT1 and DGAT2) inhibitors, an oral administration of 6f exhibited inhibition of the incorporation of deuterium labeled glycerol into TAG in this mouse model. The availability of a potent and selective chemical tool and a humanized mouse model described in this report should facilitate further dissection of the physiological function of MGAT3 and its role in lipid homeostasis. PMID- 26258603 TI - Strongyloides stercoralis infection in patients with systemic lupus erythematosus: diagnosis and prevention of severe strongyloidiasis. AB - AIM: Strongyloides stercoralis infection is usually chronic and asymptomatic and may persist undiagnosed for decades. However, in immunocompromised individuals, the infection can cause hyperinfection and dissemination. Therefore, early diagnosis is essential to prevent severe forms of strongyloidiasis. The aims of this study were: (i) to evaluate the frequency of S. stercoralis infection in patients with systemic lupus erythematous (SLE) and (ii) to estimate specific immunoglobulins G (IgG) and E (IgE) production using an enzyme-linked immunosorbent assay (ELISA) method. METHODS: Seventy-five SLE patients treated with prophylactic anthelmintic therapy were evaluated using the spontaneous sedimentation (SS), Baermann-Moraes (BM) and agar plate culture (APC) methods. Serum anti-S. stercoralis IgG and IgE antibodies were measured by ELISA. RESULTS: Using parasitological methods, the frequency of intestinal parasites was 10.7%, whereas the frequency of S. stercoralis infection was 1.3%. The sensitivity of the ELISA to detect anti-S. stercoralis IgG and IgE was 80% and 76.9%, respectively. Both assays presented the same specificity of 96.7%. The frequency of anti-S. stercoralis IgG and IgE was 16% and 28%, respectively. Six patients were positive for both antibodies. CONCLUSIONS: Diagnostic approaches using high sensitivity parasitological methods and the detection of specific antibodies are essential for the diagnosis of strongyloidiasis in immunocompromised patients. Early detection of infection can alter the course of the disease via appropriate treatment, preventing the occurrence of severe strongyloidiasis. PMID- 26258604 TI - Clinical Utility of Acetylcholine Receptor Antibody Testing in Ocular Myasthenia Gravis. AB - IMPORTANCE: The sensitivity of acetylcholine receptor (AChR) antibody testing is thought to be lower in ocular myasthenia gravis (OMG) compared with generalized disease, although estimates in small-scale studies vary. There is little information in the literature about the implications of AChR antibody levels and progression from OMG to generalized myasthenia gravis. OBJECTIVES: To test the hypothesis that serum AChR antibody testing is more sensitive in OMG than previously reported and to examine the association between AChR antibody levels and progression from OMG to generalized myasthenia gravis. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, observational cohort study was conducted of 223 patients (mean [SD] age, 59.2 [16.4] years; 139 [62.3%] male) diagnosed with OMG between July 1, 1986, and May 31, 2013, at 2 large, academic medical centers. MAIN OUTCOMES AND MEASURES: Baseline characteristics, OMG symptoms, results of AChR antibody testing, and progression time to generalized myasthenia gravis (if this occurred) were recorded for each patient. Multiple logistic regression was used to measure the association between all clinical variables and antibody result. Kaplan-Meier survival analysis was performed to examine time to generalization. RESULTS: Among the 223 participants, AChR antibody testing results were positive in 158 participants (70.9%). In an adjusted model, increased age at diagnosis (odds ratio [OR], 1.03; 95% CI, 1.01-1.04; P = .007) and progression to generalized myasthenia gravis (OR, 2.92; 95% CI, 1.18-7.26; P = .02) were significantly associated with positive antibody test results. Women were less likely to have a positive antibody test result (OR, 0.36; 95% CI, 0.19 0.68; P = .002). Patients who developed symptoms of generalized myasthenia gravis had a significantly higher mean (SD) antibody level than those who did not develop symptoms of generalized myasthenia gravis (12.7 [16.5] nmol/L vs 4.2 [7.9] nmol/L; P = .002). CONCLUSIONS AND RELEVANCE: We demonstrate a higher sensitivity of AChR antibody testing than previously reported in the largest cohort of patients with OMG available to date. Older age, male sex, and progression to generalized myasthenia gravis were significantly associated with a positive antibody test result. In addition, to our knowledge, this is the first report of an association between high AChR antibody levels and progression from OMG to generalized disease. PMID- 26258605 TI - The Moral Economy of Lying: Subjectcraft, Narrative Capital, and Uncertainty in the Politics of Asylum. AB - Based on narratives of asylum-seekers from sub-Saharan Africa in northern Italy, in this article I analyze the narrative strategies used by immigrants to meet the eligibility criteria established by asylum law. For many of them, this means "arranging" biographical details within what I call "a moral economy of lying." The first question I discuss is what types of experience and 'subject positions' these narrative strategies reveal or generate. I then examine the arbitrariness and the bureaucratic violence of the asylum evaluation process, and the role of these procedures in the making of nation-language and current technologies of citizenship. Finally, I consider the politics of testification, recognition, and memory these discourses and practices combine to shape. I analyze these issues from an historical point of view of the politics of identity, truth, and falsehood as imposed in a recent past by colonizers onto the colonized. PMID- 26258606 TI - A Teach-Discover-Treat Application of ZincPharmer: An Online Interactive Pharmacophore Modeling and Virtual Screening Tool. AB - The 2012 Teach-Discover-Treat (TDT) community-wide experiment provided a unique opportunity to test prospective virtual screening protocols targeting the anti malarial target dihydroorotate dehydrogenase (DHODH). Facilitated by ZincPharmer, an open access online interactive pharmacophore search of the ZINC database, the experience resulted in the development of a novel classification scheme that successfully predicted the bound structure of a non-triazolopyrimidine inhibitor, as well as an overall hit rate of 27% of tested active compounds from multiple novel chemical scaffolds. The general approach entailed exhaustively building and screening sparse pharmacophore models comprising of a minimum of three features for each bound ligand in all available DHODH co-crystals and iteratively adding features that increased the number of known binders returned by the query. Collectively, the TDT experiment provided a unique opportunity to teach computational methods of drug discovery, develop innovative methodologies and prospectively discover new compounds active against DHODH. PMID- 26258607 TI - Asialoglycoprotein Receptor-Mediated Gene Delivery to Hepatocytes Using Galactosylated Polymers. AB - Highly efficient, specific, and nontoxic gene delivery vector is required for gene therapy to the liver. Hepatocytes exclusively express asialoglycoprotein receptor (ASGPR), which can recognize and bind to galactose or N acetylgalactosamine. Galactosylated polymers are therefore explored for targeted gene delivery to the liver. A library of safe and stable galactose-based glycopolymers that can specifically deliver genes to hepatocytes were synthesized having different architectures, compositions, and molecular weights via the reversible addition-fragmentation chain transfer process. The physical and chemical properties of these polymers have a great impact on gene delivery efficacy into hepatocytes, as such block copolymers are found to form more stable complexes with plasmid and have high gene delivery efficiency into ASGPR expressing hepatocytes. Transfection efficiency and uptake of polyplexes with these polymers decreased significantly by preincubation of hepatocytes with free asialofetuin or by adding free asialofetuin together with polyplexes into hepatocytes. The results confirmed that polyplexes with these polymers were taken up specifically by hepatocytes via ASGPR-mediated endocytosis. The results from transfection efficiency and uptake of these polymers in cells without ASGPR, such as SK Hep1 and HeLa cells, further support this mechanism. Since in vitro cytotoxicity assays prove these glycopolymers to be nontoxic, they may be useful for delivery of clinically important genes specifically to the liver. PMID- 26258608 TI - Religion/spirituality and health in the context of cancer: Cross-domain integration, unresolved issues, and future directions. PMID- 26258609 TI - Evaluating Common Humoral Responses against Fungal Infections with Yeast Protein Microarrays. AB - We profiled the global immunoglobulin response against fungal infection by using yeast protein microarrays. Groups of CD-1 mice were infected systemically with human fungal pathogens (Coccidioides posadasii, Candida albicans, or Paracoccidioides brasiliensis) or inoculated with PBS as a control. Another group was inoculated with heat-killed yeast (HKY) of Saccharomyces cerevisiae. After 30 days, serum from mice in the groups were collected and used to probe S. cerevisiae protein microarrays containing 4800 full-length glutathione S transferase (GST)-fusion proteins. Antimouse IgG conjugated with Alexafluor 555 and anti-GST antibody conjugated with Alexafluor 647 were used to detect antibody antigen interactions and the presence of GST-fusion proteins, respectively. Serum after infection with C. albicans reacted with 121 proteins: C. posadasii, 81; P. brasiliensis, 67; and after HKY, 63 proteins on the yeast protein microarray, respectively. We identified a set of 16 antigenic proteins that were shared across the three fungal pathogens. These include retrotransposon capsid proteins, heat shock proteins, and mitochondrial proteins. Five of these proteins were identified in our previous study of fungal cell wall by mass spectrometry (Ann. N. Y. Acad. Sci. 2012, 1273, 44-51). The results obtained give a comprehensive view of the immunological responses to fungal infections at the proteomic level. They also offer insight into immunoreactive protein commonality among several fungal pathogens and provide a basis for a panfungal vaccine. PMID- 26258610 TI - The Relationship Between Helicobacter pylori Infection and Open-Angle Glaucoma: A Meta-Analysis. AB - PURPOSE: Previous studies assessed the associations between Helicobacter pylori infection and open-angle glaucoma (OAG) and produced inconsistent results. Therefore, we performed a meta-analysis to evaluate the effects of H. pylori infection on OAG risk. METHODS: Relevant studies that reported the associations between H. pylori infection and OAG were identified through an extensive search of the Exerpta Medica Database (EMBASE), Web of Science, and PubMed databases in English and Chinese National Knowledge Infrastructure, VIP, and Wan Fang databases in Chinese, and by reviewing the reference lists of the key articles. The summary odds ratio (OR) and 95% confidence interval (CI) were calculated using the random-effects model. RESULTS: This meta-analysis involved 695 glaucoma patients and 1580 control individuals. The overall combined ORs showed a significant correlation between H. pylori infection and OAG (OR = 2.08, 95% CI = 1.42-3.04). The subgroup analysis showed the association of H. pylori infection with primary open-angle glaucoma (POAG; OR = 3.06, 95% CI = 1.27-2.46) and normal tension glaucoma (NTG; OR = 1.77, 95% CI = 1.76-5.34), but not with pseudoexfoliation glaucoma (PXFG; OR = 1.46, 95% CI = 0.40-5.30). CONCLUSIONS: The result of this meta-analysis suggested a statistically significant association between H. pylori infection and OAG. Further analysis showed that this positive relation is observed only in POAG and NTG patients, but not in the PXFG patients. PMID- 26258611 TI - Relationship Between Nocturnal Intraocular Pressure Elevation and Diurnal Intraocular Pressure Level in Normal-Tension Glaucoma Patients. AB - PURPOSE: We studied the relationship between nocturnal habitual position IOP elevation and diurnal IOP level in normal-tension glaucoma (NTG) patients. METHODS: A total of 70 young NTG patients with a low diurnal IOP level (mean diurnal seated IOP < 15.0 mm Hg; low IOP group) and 79 age-, axial length-, and disease severity-matched NTG patients with a high diurnal IOP level (mean diurnal seated IOP >= 15.0 mm Hg; high IOP group) were recruited prospectively. Intraocular pressure was recorded 11 times over a 24-hour period by a single, well-trained ophthalmology resident using a hand-held tonometer. RESULTS: The mean habitual position IOP during nighttime (14.2 mm Hg) was significantly higher than that of daytime (12.8 mm Hg) in the low IOP group (P < 0.001), whereas no such difference was found in the high IOP group (16.4 vs. 16.3 mm Hg, P = 0.706). The low IOP group showed an overall nocturnal acrophase in habitual-position IOP, with 11 patients (15.7%) having a diurnal, 30 (42.8%) a nocturnal, and 29 (41.4%) no evident acrophase. By contrast, the high IOP group showed no evident peak in habitual-position IOP, with 28 patients (35.4%) having a diurnal, 12 (15.2%) a nocturnal, and 39 (49.4%) no evident acrophase. CONCLUSIONS: In NTG eyes with a low diurnal IOP, there are significant IOP increases at nighttime in the habitual position, whereas there is no significant nocturnal IOP elevation in NTG eyes with a high diurnal IOP. PMID- 26258612 TI - The Role of LOX and LOXL2 in the Pathogenesis of an Experimental Model of Choroidal Neovascularization. AB - PURPOSE: We investigated whether lysyl oxidase (LOX) and lysyl oxidase-like 2 (LOXL2) play a role in an experimental model of choroidal neovascularization (CNV). The therapeutic potential of antibodies against LOX (M64) and LOXL2 (AB0023) was evaluated in a murine laser-induced CNV model. METHODS: Expression of LOX and LOXL2 in the posterior eye cups (including retina, retinal pigment epithelium, choroid, and sclera) was studied by qRT-PCR and immunohistochemistry. In the murine model of CNV, both antibodies were administered intraperitoneally every other day until the day killed. On different time points after laser, treatment outcome was studied by immunohistochemical analysis of inflammation, angiogenesis and fibrosis, and by transcript analysis of different cytokines. RESULTS: Levels of LOX and LOXL2 in the posterior eye cups were increased after CNV-induction at different time points after laser. At day 35, their protein expression patterns appeared to correlate with retinal glial cells and endothelial cells, respectively. Both antibodies significantly inhibited fibrosis, whereas AB0023 also significantly reduced angiogenesis and inflammation. Transcript levels of alpha-1 type I collagen (COL1A1) in the posterior eye cups were significantly decreased in lasered mice treated with either M64 or AB0023. Vascular endothelial growth factor expression was also reduced only after AB0023 treatment, whereas activated fibroblast marker alpha smooth muscle actin (alphaSMA) levels were not significantly changed. CONCLUSIONS: This study suggests that LOX and LOXL2 may play an important role in the pathogenesis of AMD. Targeting LOXL2 could have a broader efficacy than targeting LOX, by reducing angiogenesis and inflammation, as well as fibrosis. PMID- 26258613 TI - Multivariate Model of the Intersubject Variability of the Retinal Nerve Fiber Layer Thickness in Healthy Subjects. AB - PURPOSE: We present and validate a multivariate model that partially compensates for retinal nerve fiber layer (RNFL) intersubject variability. METHODS: A total of 202 healthy volunteers randomly attributed to a training (TS) and a validation (VS) sample underwent complete ophthalmic examination, including Fourier-domain optical coherence tomography (FD-OCT). We acquired FD-OCT data centered at the optic disc (OD) and the macula. Two-dimensional (2D) projection images were computed and registered, to determine the distance between fovea and OD centers (FD) and their respective angle (FA). Retinal vessels were automatically segmented in the projection images and used to calculate the circumpapillary retinal vessel density (RVD) profile. Using the TS, a multivariate model was calculated for each of 256 sectors of the RNFL, including OD ratio, orientation and area, RVD, FD, FA, age, and refractive error. Model selection was based on Akaike Information Criteria. The compensation effect was determined for 12 clock hour sectors, comparing the coefficients of variation (CoV) of measured and model compensated RNFL thicknesses. The model then was applied to the VS, and CoV was calculated. RESULTS: The R value for the multivariate model was, on average 0.57 (max = 0.68). Compensation reduced the CoV on average by 18%, both for the TS and VS (up to 23% and 29%), respectively. CONCLUSIONS: We have developed and validated a comprehensive multivariate model that may be used to create a narrower range of normative RNFL data, which could improve diagnostic separation between early glaucoma and healthy subjects. This, however, remains to be demonstrated in future studies. PMID- 26258614 TI - Characterization of an Early-Onset, Autosomal Recessive, Progressive Retinal Degeneration in Bengal Cats. AB - PURPOSE: A form of retinal degeneration suspected to be hereditary was discovered in a family of Bengal cats. A breeding colony was established to characterize disease progression clinically, electrophysiologically, and morphologically, and to investigate the mode of inheritance. METHODS: Affected and related cats were donated by owners for breeding trials and pedigree analysis. Kittens from test and complementation breedings underwent ophthalmic and neuro-ophthalmic examinations and ERG, and globes were evaluated using light microscopy. RESULTS: Pedigree analysis, along with test and complementation breedings, indicated autosomal recessive inheritance and suggested that this disease is nonallelic to a retinal degeneration found in Persian cats. Mutation analysis confirmed the disease is not caused by CEP290 or CRX variants found predominantly in Abyssinian and Siamese cats. Ophthalmoscopic signs of retinal degeneration were noted at 9 weeks of age and became more noticeable over the next 4 months. Visual deficits were behaviorally evident by 1 year of age. Electroretinogram demonstrated reduced rod and cone function at 7 and 9 weeks of age, respectively. Rod responses were mostly extinguished at 14 weeks of age; cone responses were minimal by 26 weeks. Histologic degeneration was first observed at 8 weeks, evidenced by reduced photoreceptor numbers, then rapid deterioration of the photoreceptor layer and, subsequently, severe outer retinal degeneration. CONCLUSIONS: A recessively inherited primary photoreceptor degeneration was characterized in the Bengal cat. The disease is characterized by early onset, with histologic, ophthalmoscopic, and electrophysiological signs evident by 2 months of age, and rapid progression to blindness. PMID- 26258615 TI - Lens Position and Age: The Central India Eye and Medical Study. AB - PURPOSE: We assessed changes in the position of the lens with aging in a general population. METHODS: The population-based Central India Eye and Medical Study included 4711 subjects. As part of an ophthalmic examination, anterior segment length (ASL) was measured sonographically and calculated as anterior chamber depth plus lens thickness. Subjects with nuclear cataract grades 5 or more (43.9% of the sample) were excluded. RESULTS: The study included 2468 subjects (1176 [47.6%] men) with a mean age of 41.2 +/- 8.5 years (range, 30-78 years) and mean axial length of 22.68 +/- 0.81 mm (range, 19.89-31.02 mm). In multivariate analysis, longer ASL was associated with older age (P = 0.04; correlation coefficient B, 0.002; 95% confidence interval [CI], 0.000, 0.005) after adjusting for male sex (P < 0.001), longer axial length (P < 0.001), higher degree of nuclear cataract (P = 0.001), and higher body mass index (P = 0.02). Greater lens thickness was associated with older age (P < 0.001; B, 0.009; 95% CI, 0.007, 0.0011) after adjusting for male sex (P < 0.001), shallower anterior chamber depth (P < 0.001), and higher degree of nuclear cataract (P < 0.001). Deeper anterior chamber depth was associated with younger age (P < 0.001; B, -0.007; 95% CI, -0.008, -0.005) after adjusting for male sex (P < 0.001), thinner lens thickness (P < 0.001), and longer axial length (P < 0.001). Combining both analyses revealed that for each year increase in age, lens thickness increased by 0.009 mm, anterior chamber depth decreased by 0.007 mm, the posterior lens pole moved backward by 0.002 mm, and the lens center moved forward by 0.0025 mm. CONCLUSIONS: Increasing age before the development of cataract is associated with a slight forward movement of the lens center, adding to the lens paradox. PMID- 26258617 TI - Alteration of N-Glycan Profiles in Diabetic Retinopathy. AB - PURPOSE: To investigate the alteration of vitreal N-glycans in patients with proliferative diabetic retinopathy (PDR). METHODS: Plasma and vitreous samples were collected from 17 patients (10 females and 7 males) with PDR (PDR group) and 17 nondiabetic patients (8 females and 9 males) with epiretinal membrane (ERM) and idiopathic macular hole (MH) (non-diabetes mellitus [DM] group). Profiles of N-glycans were analyzed by a glycoblotting-based high-throughput protocol that we recently developed. Human retinal microvascular endothelial cells (HRMECs) were cultivated with culture media containing either low glucose (5 mM) or high glucose (25 mM), and expression levels of sialyltransferases were analyzed by real-time PCR and ELISA. RESULTS: Amount of N-glycans in the vitreous fluid of the PDR group was significantly higher than that of the non-DM group (495.5 +/- 37.4 vs. 142.7 +/- 30.8 pmol/100 MUg protein, P < 0.005), whereas there was no significant difference in the plasma samples between the PDR and the non-DM group. In addition, profile analysis showed that N-glycans with sialic acids increased in the vitreous of the PDR group (328.4 +/- 25.8 pmol/100 MUg protein) compared to the non-DM group (92.1 +/- 21.2 pmol/100 MUg protein, P < 0.0005). Expression levels of sialyltransferases ST3GAL1 and ST3GAL4 were upregulated in the HRMECs after high-glucose stimulation. Consistent with the real-time PCR data, high-glucose stimulation elevated the protein levels of ST3GAL1 (117.4 +/- 14.9 pg/mg, P < 0.01) and ST3GAL4 (6.1 +/- 0.9 pg/mg, P < 0.05) in the HRMECs compared with the cells cultured with low-glucose culture media (ST3GAL1, 64.4 +/ 5.8 pg/mg; ST3GAL4, 3.8 +/- 0.3 pg/mg). CONCLUSIONS: Our data demonstrate distinct changes in the N-glycan profile and an increase in sialylated N-glycans in eyes with PDR. PMID- 26258618 TI - Switchable Pickering Emulsions Stabilized by Awakened TiO2 Nanoparticle Emulsifiers Using UV/Dark Actuation. AB - In this work, switchable Pickering emulsions that utilize UV/dark manipulation employ a type of smart TiO2 nanoparticle as emulsifiers. The emulsifiers can be awakened when needed via UV-induced degradation of grafted silanes on TiO2 nanoparticles. By tuning the surface wettability of TiO2 nanoparticles in situ via UV/dark actuation, emulsions stabilized by the nanoparticles can be reversibly switched between the water-in-oil (W/O) type and oil-in-water (O/W) type for several cycles. Due to the convertible wettability, the smart nanoparticle emulsifiers can be settled in either the oil phase or the water phase as desired during phase separation, making it convenient for recycling. The present work provides a facile and noninvasive method to freely manipulate the formation, breakage, and switching of the emulsion; this method has promising potential as a powerful technique for use in energy-efficient and environmentally friendly industries. PMID- 26258619 TI - [Complications after Percutaneous Endoscopic Gastrostomy Tube Placement - A Retrospective Analysis]. AB - BACKGROUND: Enteral nutrition is vital for patients with inadequate or absent oral food intake, as it can help to avoid catabolic metabolism. Enteral feeding can be secured by placing a percutaneous endoscopic gastrostomy tube (PEG-tube) which is an approved method. Several clinical studies could verify the superiority of this procedure compared to other options. Even though PEG-tube placement is regarded as less invasive surgery, a considerable rate of complications is reported in literature. MATERIAL/METHODS: Here, we report a retrospective analysis of PEG-tube placements in the Bonn University Hospital from January 2005 to December 2012. RESULTS: Overall, 641 PEG-tubes were placed with a complication rate of 9.4 %, which can be further divided in 5.5 % minor complications (mic) and 3.9 % major complications (mac). Two cases of death occurred in the context of PEG-tube placement. Endoscopically inserted PEG-tubes showed a complication rate of 8.6 % (4.8 % mic, 3.8 % mac). 63.2 % of mac consisted of perforations, 15.8 % of intra-abdominal abscesses and 15.8 % of buried bumper syndromes. The complication rate of CT-guided placement of PEG tubes was 38.9 % (27.8 % mic, 11.1 % mac). In this group, all mac were perforations. Surgical PEG-tube placement was accompanied by no mac and 7.7 % mic. CONCLUSION: The amount of complications during PEG-tube placement is remarkable, therefore the indication of this procedure must be contemplated critically and careful follow-up is crucial. PMID- 26258620 TI - [Computed Tomography-Based Planimetry of the Pancreatic Transection Line in Risk Evaluation for Postoperative Pancreatic Fistula after Pancreatic Head Resection]. AB - BACKGROUND: Postoperative pancreatic fistula is a relevant complication after pancreatoduodenectomy. Therefore, preoperative detection of high risk patients may be important. We evaluated preoperative CT-imaging by planimetry at the expected resection plane along the superior mesenteric vein and correlated the results with the incidence of postoperative pancreatic fistula. PATIENTS AND METHODS: From 2009 to 2013, 123 patients with pancreatoduodenectomy underwent homogenous preoperative imaging and reconstruction of the pancreatojejunostomy. Planimetry was performed at a multiplanar reconstruction of the pancreatic transection plane (diameter, range, duct width, area) as well as the calculation of ratios (duct width/pancreatic diameter; D/P-ratio). The measured values were correlated with the incidence of postoperative pancreatic fistula. RESULTS: Planimetry showed a significant difference of the pancreatic transection plane in relation to the incidence of postoperative pancreatic fistula. A thick parenchyma and a tiny duct are significant risk factors. In 84 % or, respectively, 94 % of the patients with postoperative pancreatic fistula, a duct width of less than 20 % of the pancreatic diameter was observed (D/P ratio < 0.2; p < 0.01). The D/P ratio was the only independent risk factor in multivariate analysis. DISCUSSION: The incidence of postoperative pancreatic fistula correlates significantly with the morphology of the pancreatic transection plane. The risk increases significantly with a D/P ratio of < 0.2. PMID- 26258621 TI - [Young Women - Problematic Patients in Vascular Surgery]. AB - The treatment of peripheral arterial disease (PAD) in young women between 40 and 60 years of age represents a difficult challenge for the vascular surgeon. Excessive smoking, an early menopause and the unfavourable anatomic proportions of thinner arterial vessels or vein grafts during peripheral bypass-surgery lead to a higher rate of complications or re-occlusion following invasive therapy in comparison to male patients. A special anatomic manifestation appearing nearly only in women around the 6th decade is the so-called aortoiliac hypoplastic syndrome with a high rate of re-occlusion after balloon-dilatation or local thrombendarteriectomy and bypass grafting, respectively. Variabilities in coagulation and the undertreatment of classical risk factors of PAD by medical drugs lead to poorer results in the treatment of PAD in young women. Therefore a conservative therapy - whenever feasible - should be the first choice for treating PAD in young women. PMID- 26258622 TI - Androgen Receptor Coactivator ARID4B Is Required for the Function of Sertoli Cells in Spermatogenesis. AB - Defects in spermatogenesis, a process that produces spermatozoa inside seminiferous tubules of the testis, result in male infertility. Spermatogenic progression is highly dependent on a microenvironment provided by Sertoli cells, the only somatic cells and epithelium of seminiferous tubules. However, genes that regulate such an important activity of Sertoli cells are poorly understood. Here, we found that AT-rich interactive domain 4B (ARID4B), is essential for the function of Sertoli cells to regulate spermatogenesis. Specifically, we generated Sertoli cell-specific Arid4b knockout (Arid4bSCKO) mice, and showed that the Arid4bSCKO male mice were completely infertile with impaired testis development and significantly reduced testis size. Importantly, severe structural defects accompanied by loss of germ cells and Sertoli cell-only phenotype were found in many seminiferous tubules of the Arid4bSCKO testes. In addition, maturation of Sertoli cells was significantly delayed in the Arid4bSCKO mice, associated with delayed onset of spermatogenesis. Spermatogenic progression was also defective, showing an arrest at the round spermatid stage in the Arid4bSCKO testes. Interestingly, we showed that ARID4B functions as a "coactivator" of androgen receptor and is required for optimal transcriptional activation of reproductive homeobox 5, an androgen receptor target gene specifically expressed in Sertoli cells and critical for spermatogenesis. Together, our study identified ARID4B to be a key regulator of Sertoli cell function important for male germ cell development. PMID- 26258624 TI - Lower mitochondrial DNA copy number in peripheral blood leukocytes increases the risk of endometrial cancer. AB - Mitochondria are the primary source of energy generation in human cells. Low mitochondrial DNA (mtDNA) copy number in peripheral blood leukocytes (PBLs) has been associated with obesity and increased risks of several cancers. Since obesity is a significant risk factor for endometrial cancer, we hypothesize that low mtDNA copy number in PBLs is associated with an increased susceptibility to endometrial cancer. Using a Caucasian case-control study, we measured mtDNA copy number in PBLs from 139 endometrial cancer patients and 139 age-matched controls and determined the association of mtDNA copy number with the risk of endometrial cancer using multivariate logistic regression analysis. The normalized mtDNA copy number was significantly lower in endometrial cancer cases (median, 0.84; range, 0.24-2.00) than in controls (median, 1.06; range, 0.64-1.96) (P < 0.001). Dichotomized into high and low groups based on the median mtDNA copy number value in the controls, individuals with low mtDNA copy number had a significantly increased risk of endometrial cancer (adjusted OR, 5.59; 95%CI, 3.05-10.25; P < 0.001) compared to those with high mtDNA copy number. There was a significant dose-response association in tertile analysis. In addition, there was a significant joint effect between lower mtDNA copy number and never smoking, hypertension, diabetes, and obesity in elevating the risk of endometrial cancer. Low mtDNA copy number in PBLs is significantly associated with an increased risk of endometrial cancer in Caucasians. (c) 2015 Wiley Periodicals, Inc. PMID- 26258623 TI - Limitations to oxygen transport and utilization during sprint exercise in humans: evidence for a functional reserve in muscle O2 diffusing capacity. AB - To determine the contribution of convective and diffusive limitations to V(O2peak) during exercise in humans, oxygen transport and haemodynamics were measured in 11 men (22 +/- 2 years) during incremental (IE) and 30 s all-out cycling sprints (Wingate test, WgT), in normoxia (Nx, P(IO2): 143 mmHg) and hypoxia (Hyp, P(IO2): 73 mmHg). Carboxyhaemoglobin (COHb) was increased to 6-7% before both WgTs to left-shift the oxyhaemoglobin dissociation curve. Leg V(O2) was measured by the Fick method and leg blood flow (BF) with thermodilution, and muscle O2 diffusing capacity (D(MO2)) was calculated. In the WgT mean power output, leg BF, leg O2 delivery and leg V(O2) were 7, 5, 28 and 23% lower in Hyp than Nx (P < 0.05); however, peak WgT D(MO2) was higher in Hyp (51.5 +/- 9.7) than Nx (20.5 +/- 3.0 ml min(-1) mmHg(-1), P < 0.05). Despite a similar P(aO2) (33.3 +/- 2.4 and 34.1 +/- 3.3 mmHg), mean capillary P(O2) (16.7 +/- 1.2 and 17.1 +/- 1.6 mmHg), and peak perfusion during IE and WgT in Hyp, D(MO2) and leg V(O2) were 12 and 14% higher, respectively, during WgT than IE in Hyp (both P < 0.05). D(MO2) was insensitive to COHb (COHb: 0.7 vs. 7%, in IE Hyp and WgT Hyp). At exhaustion, the Y equilibration index was well above 1.0 in both conditions, reflecting greater convective than diffusive limitation to the O2 transfer in both Nx and Hyp. In conclusion, muscle V(O2) during sprint exercise is not limited by O2 delivery, O2 offloading from haemoglobin or structure-dependent diffusion constraints in the skeletal muscle. These findings reveal a remarkable functional reserve in muscle O2 diffusing capacity. PMID- 26258625 TI - Intravascular ultrasonic-photoacoustic (IVUP) endoscope with 2.2-mm diameter catheter for medical imaging. AB - Intravascular ultrasound (IVUS) imaging is extremely important for detection and characterization of high-risk atherosclerotic plaques as well as gastrointestinal diseases. Recently, intravascular photoacoustic (IVPA) imaging has been used to differentiate the composition of biological tissues with high optical contrast and ultrasonic resolution. The combination of these imaging techniques could provide morphological information and molecular screening to characterize abnormal tissues, which would help physicians to ensure vital therapeutic value and prognostic significance for patients before commencing therapy. In this study, integration of a high-frequency IVUS imaging catheter (45MHz, single element, unfocused, 0.7mm in diameter) with a multi-mode optical fiber (0.6mm in core diameter, 0.22 NA), an integrated intravascular ultrasonic-photoacoustic (IVUP) imaging catheter, was developed to provide spatial and functional information on light distribution in a turbid sample. Simultaneously, IVUS imaging was co-registered to IVPA imaging to construct 3D volumetric sample images. In a phantom study, a polyvinyl alcohol (PVA) tissue-mimicking arterial vessel phantom with indocyanine green (ICG) and methylene blue (MB) inclusion was used to demonstrate the feasibility of mapping the biological dyes, which are used in cardiovascular and cancer diagnostics. For the ex vivo study, an excised sample of pig intestine with ICG was utilized to target the biomarkers present in the gastrointestinal tumors or the atherosclerotic plaques with the proposed hybrid technique. The results indicated that IVUP endoscope with the 2.2-mm diameter catheter could be a useful tool for medical imaging. PMID- 26258626 TI - Cigarette smoke extract induces apoptosis of rat alveolar Type II cells via the PLTP/TGF-beta1/Smad2 pathway. AB - Apoptosis of alveolar epithelial cells has been implicated in the pathogenesis of acute lung injury. Phospholipid transfer protein (PLTP) may play a role in apoptosis. In the present study, the effect of the novel function of PLTP in cigarette smoke extract (CSE)-induced apoptosis of alveolar epithelial cells and the possible mechanism were examined. Male Wistar rats were exposed to air and cigarette smoke (n=10/exposure) for 6h/day on 3 consecutive days, then the lungs were sectioned and examined. To investigate effects on alveolar epithelial cells, rat alveolar epithelial cells (RLE-6TN) were treated with different concentrations of CSE for various times. siRNA for PLTP was transfected into cells and an inhibitor of the transforming growth factor-beta1 (TGF-beta1) type I receptor was administered prior to CSE exposure. Apoptosis was measured, and mRNA expression of PLTP and TGF-beta1 and protein levels of PLTP, TGF-beta1, p-Smad2 and cleaved caspase-3 were analyzed. The results showed that apoptosis, as well as expression of PLTP, TGF-beta1, p-Smad2 and cleaved caspase-3 were all significantly increased after CSE stimulation (P<0.05). Furthermore, the expression of TGF-beta1, p-Smad2 and cleaved caspase-3 induced by CSE could be partly abrogated by knockdown of PLTP. The expression of PLTP showed no significant change as a result of TGF-beta1 receptor inhibition, while cleaved caspase-3 showed a remarkable reduction. PLTP may act as an upstream signal molecule of the TGF-beta1/Smad2 pathway and is likely to be involved in CSE induced apoptosis of alveolar epithelial cells. PMID- 26258627 TI - Primary Posttransplant Plasmablastic Lymphoma of the Tongue: Report of a Case With Immunohistochemical and Molecular Studies. AB - Plasmablastic lymphoma is a rare, highly aggressive lymphoma characterized by large lymphoid cells with immunoblastic or plasmablastic features, absent expression of CD45 and CD20, positivity for CD138, and monoclonal rearrangement of the immunoglobulin heavy chain gene. It was originally reported in oral cavity in the setting of underlying human immunodeficiency viral infection but may occur also in lymph nodes or extranodal sites after transplantation and, more rarely, immunocompetent patients. Herein, we report a case of PBL presenting as an ulcerated lesion of the tongue in an HIV-negative patient, 6 years after renal transplantation. To date, only rare cases of plasmablastic lymphoma presenting after solid organ transplantation have been reported. Although a reduction of immunosuppression and an aggressive chemotherapy were performed, the patient died after a few months because of septic and cardiovascular complications. PMID- 26258628 TI - Nitrogen-Doping Induced Self-Assembly of Graphene Nanoribbon-Based Two Dimensional and Three-Dimensional Metamaterials. AB - Narrow graphene nanoribbons (GNRs) constructed by atomically precise bottom-up synthesis from molecular precursors have attracted significant interest as promising materials for nanoelectronics. But there has been little awareness of the potential of GNRs to serve as nanoscale building blocks of novel materials. Here we show that the substitutional doping with nitrogen atoms can trigger the hierarchical self-assembly of GNRs into ordered metamaterials. We use GNRs doped with eight N atoms per unit cell and their undoped analogues, synthesized using both surface-assisted and solution approaches, to study this self-assembly on a support and in an unrestricted three-dimensional (3D) solution environment. On a surface, N-doping mediates the formation of hydrogen-bonded GNR sheets. In solution, sheets of side-by-side coordinated GNRs can in turn assemble via van der Waals and pi-stacking interactions into 3D stacks, a process that ultimately produces macroscopic crystalline structures. The optoelectronic properties of these semiconducting GNR crystals are determined entirely by those of the individual nanoscale constituents, which are tunable by varying their width, edge orientation, termination, and so forth. The atomically precise bottom-up synthesis of bulk quantities of basic nanoribbon units and their subsequent self assembly into crystalline structures suggests that the rapidly developing toolset of organic and polymer chemistry can be harnessed to realize families of novel carbon-based materials with engineered properties. PMID- 26258629 TI - Biological evaluation of two Keggin-type polyoxometalates containing glycine as mushroom tyrosinase inhibitors. AB - Two Keggin-type polyoxometalates (POMs) containing glycine, (HGly)3 PW12 O40 and (HGly)4 SiW12 O40 , were synthesized and evaluated as mushroom tyrosinase inhibitors. The spectrophotometric method results showed that both (HGly)3 PW12 O40 and (HGly)4 SiW12 O40 could strongly inhibit the diphenolase activity of the tyrosinase and that their inhibition mechanisms were reversible. Their half inhibition concentration values were estimated to be 1.55 and 1.39 mmol/L, respectively. The inhibition kinetics analysis by Lineweaver-Burk plots indicated that (HGly)3 PW12 O40 was an uncompetitive inhibitor with KIS = 0.046 mmol/L, whereas (HGly)4 SiW12 O40 was a noncompetitive inhibitor with KI = KIS = 2.17 mmol/L. This study may help to extend the application of POMs in the fields of medicine and food preservation. PMID- 26258630 TI - In Situ Method for Measuring the Mechanical Properties of Nafion Thin Films during Hydration Cycles. AB - Perfluorinated ionomers, in particular Nafion, are an essential component in hydrogen fuel cells, as both the proton exchange membrane and the binder within the catalyst layer. During normal operation of a hydrogen fuel cell, the ionomer will progressively swell and deswell in response to the changes in hydration, resulting in mechanical fatigue and ultimately failure over time. In this study, we have developed and implemented a cantilever bending technique in order to investigate the swelling-induced stresses in biaxially constrained Nafion thin films. When the deflection of a cantilever beam coated with a polymer film is monitored as it is exposed to varying humidity environments, the swelling induced stress-thickness product of the polymer film is measured. By combining the stress thickness results with a measurement of the swelling strain as a function of humidity, as measured by quartz crystal microbalance (QCM) and X-ray reflectivity (XR), the swelling stress can be determined. An estimate of the Young's modulus of thin Nafion films as a function of relative humidity is obtained. The Young's modulus values indicate orientation of the ionic domains within the polymer films, which were confirmed by grazing incidence small-angle X-ray scattering (GISAXS). This study represents a measurement platform that can be expanded to incorporate novel ionomer systems and fuel cell components to mimic the stress state of a working hydrogen fuel cell. PMID- 26258631 TI - Adaptive changes in the kinetochore architecture facilitate proper spindle assembly. AB - Mitotic spindle formation relies on the stochastic capture of microtubules at kinetochores. Kinetochore architecture affects the efficiency and fidelity of this process with large kinetochores expected to accelerate assembly at the expense of accuracy, and smaller kinetochores to suppress errors at the expense of efficiency. We demonstrate that on mitotic entry, kinetochores in cultured human cells form large crescents that subsequently compact into discrete structures on opposite sides of the centromere. This compaction occurs only after the formation of end-on microtubule attachments. Live-cell microscopy reveals that centromere rotation mediated by lateral kinetochore-microtubule interactions precedes the formation of end-on attachments and kinetochore compaction. Computational analyses of kinetochore expansion-compaction in the context of lateral interactions correctly predict experimentally observed spindle assembly times with reasonable error rates. The computational model suggests that larger kinetochores reduce both errors and assembly times, which can explain the robustness of spindle assembly and the functional significance of enlarged kinetochores. PMID- 26258632 TI - Mad1 promotes chromosome congression by anchoring a kinesin motor to the kinetochore. AB - For proper partitioning of genomes in mitosis, all chromosomes must be aligned at the spindle equator before the onset of anaphase. The spindle assembly checkpoint (SAC) monitors this process, generating a 'wait anaphase' signal at unattached kinetochores of misaligned chromosomes. However, the link between SAC activation and chromosome alignment is poorly understood. Here we show that Mad1, a core SAC component, plays a hitherto concealed role in chromosome alignment. Protein protein interaction screening revealed that fission yeast Mad1 binds the plus-end directed kinesin-5 motor protein Cut7 (Eg5 homologue), which is generally thought to promote spindle bipolarity. We demonstrate that Mad1 recruits Cut7 to kinetochores of misaligned chromosomes and promotes chromosome gliding towards the spindle equator. Similarly, human Mad1 recruits another kinetochore motor CENP-E, revealing that Mad1 is the conserved dual-function protein acting in SAC activation and chromosome gliding. Our results suggest that the mitotic checkpoint has co-evolved with a mechanism to drive chromosome congression. PMID- 26258634 TI - Guardianship and End-of-Life Decision Making. AB - As the population ages, more adults will develop impaired decision-making capacity and have no family members or friends available to make medical decisions on their behalf. In such situations, a professional guardian is often appointed by the court. This official has no preexisting relationship with the impaired individual but is paid to serve as a surrogate decision maker. When a professional guardian is faced with decisions concerning life-sustaining treatment, substituted judgment may be impossible, and reports have repeatedly suggested that guardians are reluctant to make the decision to limit care. Physicians are well positioned to assist guardians with these decisions and safeguard the rights of the vulnerable persons they represent. Doing so effectively requires knowledge of the laws governing end-of-life decisions by guardians. However, physicians are often uncertain about whether guardians are empowered to withhold treatment and when their decisions require judicial review. To address this issue, we analyzed state guardianship statutes and reviewed recent legal cases to characterize the authority of a guardian over choices about end-of-life treatment. We found that most state guardianship statutes have no language about end-of-life decisions. We identified 5 legal cases during the past decade that addressed a guardian's authority over these decisions, and only 1 case provided a broad framework applicable to clinical practice. Work to improve end-of-life decision making by guardians may benefit from a multidisciplinary effort to develop comprehensive standards to guide clinicians and guardians when treatment decisions need to be made. PMID- 26258633 TI - Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth. AB - YAP/TAZ are nuclear effectors of the Hippo pathway regulating organ growth and tumorigenesis. Yet, their function as transcriptional regulators remains underinvestigated. By ChIP-seq analyses in breast cancer cells, we discovered that the YAP/TAZ transcriptional response is pervasively mediated by a dual element: TEAD factors, through which YAP/TAZ bind to DNA, co-occupying chromatin with activator protein-1 (AP-1, dimer of JUN and FOS proteins) at composite cis regulatory elements harbouring both TEAD and AP-1 motifs. YAP/TAZ/TEAD and AP-1 form a complex that synergistically activates target genes directly involved in the control of S-phase entry and mitosis. This control occurs almost exclusively from distal enhancers that contact target promoters through chromatin looping. YAP/TAZ-induced oncogenic growth is strongly enhanced by gain of AP-1 and severely blunted by its loss. Conversely, AP-1-promoted skin tumorigenesis is prevented in YAP/TAZ conditional knockout mice. This work highlights a new layer of signalling integration, feeding on YAP/TAZ function at the chromatin level. PMID- 26258635 TI - BT-benzo-29 inhibits bacterial cell proliferation by perturbing FtsZ assembly. AB - We have identified a potent antibacterial agent N-(4-sec-butylphenyl)-2-(thiophen 2-yl)-1H-benzo[d]imidazole-4-carboxamide (BT-benzo-29) from a library of benzimidazole derivatives that stalled bacterial division by inhibiting FtsZ assembly. A short (5 min) exposure of BT-benzo-29 disassembled the cytokinetic Z ring in Bacillus subtilis cells without affecting the cell length and nucleoids. BT-benzo-29 also perturbed the localization of early and late division proteins such as FtsA, ZapA and SepF at the mid-cell. Further, BT-benzo-29 bound to FtsZ with a dissociation constant of 24 +/- 3 MUm and inhibited the assembly and GTPase activity of purified FtsZ. A docking analysis suggested that BT-benzo-29 may bind to FtsZ at the C-terminal domain near the T7 loop. BT-benzo-29 displayed significantly weaker inhibitory effects on the assembly and GTPase activity of two mutants (L272A and V275A) of FtsZ supporting the prediction of the docking analysis. Further, BT-benzo-29 did not appear to inhibit DNA duplication and nucleoid segregation and it did not perturb the membrane potential of B. subtilis cells. The results suggested that BT-benzo-29 exerts its potent antibacterial activity by inhibiting FtsZ assembly. Interestingly, BT-benzo-29 did not affect the membrane integrity of mammalian red blood cells. BT-benzo-29 bound to tubulin with a much weaker affinity than FtsZ and exerted significantly weaker effects on mammalian cells than on the bacterial cells indicating that the compound may have a strong antibacterial potential. PMID- 26258636 TI - Crystal structures of the PsbS protein essential for photoprotection in plants. AB - The photosystem II protein PsbS has an essential role in qE-type nonphotochemical quenching, which protects plants from photodamage under excess light conditions. qE is initiated by activation of PsbS by low pH, but the mechanism of PsbS action remains elusive. Here we report the low-pH crystal structures of PsbS from spinach in its free form and in complex with the qE inhibitor N,N' dicyclohexylcarbodiimide (DCCD), revealing that PsbS adopts a unique folding pattern, and, unlike other members of the light-harvesting-complex superfamily, it is a noncanonical pigment-binding protein. Structural and biochemical evidence shows that both active and inactive PsbS form homodimers in the thylakoid membranes, and DCCD binding disrupts the lumenal intermolecular hydrogen bonds of the active PsbS dimer. Activation of PsbS by low pH during qE may involve a conformational change associated with altered lumenal intermolecular interactions of the PsbS dimer. PMID- 26258637 TI - Structure of Rab11-FIP3-Rabin8 reveals simultaneous binding of FIP3 and Rabin8 effectors to Rab11. AB - The small GTPase Rab11 and its effectors FIP3 and Rabin8 are essential to membrane-trafficking pathways required for cytokinesis and ciliogenesis. Although effector binding is generally assumed to be sequential and mutually exclusive, we show that Rab11 can simultaneously bind FIP3 and Rabin8. We determined crystal structures of human Rab11-GMPPNP-Rabin8 and Rab11-GMPPNP-FIP3-Rabin8. The structures reveal that the C-terminal domain of Rabin8 adopts a previously undescribed fold that interacts with Rab11 at an unusual effector-binding site neighboring the canonical FIP3-binding site. We show that Rab11-GMPPNP-FIP3 Rabin8 is more stable than Rab11-GMPPNP-Rabin8, owing to direct interaction between Rabin8 and FIP3 within the dual effector-bound complex. The data allow us to propose a model for how membrane-targeting complexes assemble at the trans Golgi network and recycling endosomes, through multiple weak interactions that create high-avidity complexes. PMID- 26258638 TI - Probing Galphai1 protein activation at single-amino acid resolution. AB - We present comprehensive maps at single-amino acid resolution of the residues stabilizing the human Galphai1 subunit in nucleotide- and receptor-bound states. We generated these maps by measuring the effects of alanine mutations on the stability of Galphai1 and the rhodopsin-Galphai1 complex. We identified stabilization clusters in the GTPase and helical domains responsible for structural integrity and the conformational changes associated with activation. In activation cluster I, helices alpha1 and alpha5 pack against strands beta1 beta3 to stabilize the nucleotide-bound states. In the receptor-bound state, these interactions are replaced by interactions between alpha5 and strands beta4 beta6. Key residues in this cluster are Y320, which is crucial for the stabilization of the receptor-bound state, and F336, which stabilizes nucleotide bound states. Destabilization of helix alpha1, caused by rearrangement of this activation cluster, leads to the weakening of the interdomain interface and release of GDP. PMID- 26258639 TI - A software tool for tomographic axial superresolution in STED microscopy. AB - A method for generating three-dimensional tomograms from multiple three dimensional axial projections in STimulated Emission Depletion (STED) superresolution microscopy is introduced. Our STED< method, based on the use of a micromirror placed on top of a standard microscopic sample, is used to record a three-dimensional projection at an oblique angle in relation to the main optical axis. Combining the STED< projection with the regular STED image into a single view by tomographic reconstruction, is shown to result in a tomogram with three to-four-fold improved apparent axial resolution. Registration of the different projections is based on the use of a mutual-information histogram similarity metric. Fusion of the projections into a single view is based on Richardson-Lucy iterative deconvolution algorithm, modified to work with multiple projections. Our tomographic reconstruction method is demonstrated to work with real biological STED superresolution images, including a data set with a limited signal-to-noise ratio (SNR); the reconstruction software (SuperTomo) and its source code will be released under BSD open-source license. PMID- 26258640 TI - Deficient angiogenesis in redox-dead Cys17Ser PKARIalpha knock-in mice. AB - Angiogenesis is essential for tissue development, wound healing and tissue perfusion, with its dysregulation linked to tumorigenesis, rheumatoid arthritis and heart disease. Here we show that pro-angiogenic stimuli couple to NADPH oxidase-dependent generation of oxidants that catalyse an activating intermolecular-disulphide between regulatory-RIalpha subunits of protein kinase A (PKA), which stimulates PKA-dependent ERK signalling. This is crucial to blood vessel growth as 'redox-dead' Cys17Ser RIalpha knock-in mice fully resistant to PKA disulphide-activation have deficient angiogenesis in models of hind limb ischaemia and tumour-implant growth. Disulphide-activation of PKA represents a new therapeutic target in diseases with aberrant angiogenesis. PMID- 26258641 TI - Palate Shape and Depth: A Shape-Matching and Machine Learning Method for Estimating Ancestry from Human Skeletal Remains. AB - In the past, assessing ancestry relied on the naked eye and observer experience; however, replicability has become an important aspect of such analysis through the application of metric techniques. This study examines palate shape and assesses ancestry quantitatively using a 3D digitizer and shape-matching and machine learning methods. Palate curves and depths were recorded, processed, and tested for 376 individuals. Palate shape was an accurate indicator of ancestry in 58% of cases. Cluster analysis revealed that the parabolic, hyperbolic, and elliptical shapes are discrete from one another. Preliminary results indicate that palate depth in Hispanic individuals is greatest. Palate shape appears to be a useful indicator of ancestry, particularly when assessed by a computer. However, these data suggest that palate shape is not useful for assessing ancestry in Hispanic individuals. Although ancestry may be determined from palate shape, the use of multiple features is recommended and more reliable. PMID- 26258642 TI - Formin-like2 regulates Rho/ROCK pathway to promote actin assembly and cell invasion of colorectal cancer. AB - Formin-like2 (FMNL2) is a member of the diaphanous-related formins family, which act as effectors and upstream modulators of Rho GTPases signaling and control the actin-dependent processes, such as cell motility or invasion. FMNL2 has been identified as promoting the motility and metastasis in colorectal carcinoma (CRC). However, whether FMNL2 regulates Rho signaling to promote cancer cell invasion remains unclear. In this study, we demonstrated an essential role for FMNL2 in the activations of Rho/ROCK pathway, SRF transcription or actin assembly, and subsequent CRC cell invasion. FMNL2 could activate Rho/ROCK pathway, and required ROCK to promote CRC cell invasion. Moreover, FMNL2 promoted the formation of filopodia and stress fiber, and activated the SRF transcription in a Rho-dependent manner. We also demonstrated that FMNL2 was necessary for LPA induced invasion, RhoA/ROCK activation, actin assembly and SRF activation. FMNL2 was an essential component of LPA signal transduction toward RhoA by directly interacting with LARG. LARG silence inhibited RhoA/ROCK pathway and CRC cell invasion. Collectively, these data indicate that FMNL2, acting as upstream of RhoA by interacting with LARG, can promote actin assembly and CRC cell invasion through a Rho/ROCK-dependent mechanism. PMID- 26258644 TI - A Comprehensive and Harmonized Digital Forensic Investigation Process Model. AB - Performing a digital forensic investigation (DFI) requires a standardized and formalized process. There is currently neither an international standard nor does a global, harmonized DFI process (DFIP) exist. The authors studied existing state of-the-art DFIP models and concluded that there are significant disparities pertaining to the number of processes, the scope, the hierarchical levels, and concepts applied. This paper proposes a comprehensive model that harmonizes existing models. An effort was made to incorporate all types of processes proposed by the existing models, including those aimed at achieving digital forensic readiness. The authors introduce a novel class of processes called concurrent processes. This is a novel contribution that should, together with the rest of the model, enable more efficient and effective DFI, while ensuring admissibility of digital evidence. Ultimately, the proposed model is intended to be used for different types of DFI and should lead to standardization. PMID- 26258643 TI - Endotoxin Exposure: Predictors and Prevalence of Associated Asthma Outcomes in the United States. AB - RATIONALE: Inhaled endotoxin induces airway inflammation and is an established risk factor for asthma. The 2005-2006 National Health and Nutrition Examination Survey included measures of endotoxin and allergens in homes as well as specific IgE to inhalant allergens. OBJECTIVES: To understand the relationships between endotoxin exposure, asthma outcomes, and sensitization status for 15 aeroallergens in a nationally representative sample. METHODS: Participants were administered questionnaires in their homes. Reservoir dust was vacuum sampled to generate composite bedding and bedroom floor samples. We analyzed 7,450 National Health and Nutrition Examination Survey dust and quality assurance samples for their endotoxin content using extreme quality assurance measures. Data for 6,963 subjects were available, making this the largest study of endotoxin exposure to date. Log-transformed endotoxin concentrations were analyzed using logistic models and forward stepwise linear regression. Analyses were weighted to provide national prevalence estimates and unbiased variances. MEASUREMENTS AND MAIN RESULTS: Endotoxin exposure was significantly associated with wheeze in the past 12 months, wheeze during exercise, doctor and/or emergency room visits for wheeze, and use of prescription medications for wheeze. Models adjusted for age, sex, race and/or ethnicity, and poverty-to-income ratio and stratified by allergy status showed that these relationships were not dependent upon sensitization status but were worsened among those living in poverty. Significant predictors of higher endotoxin exposures were lower family income; Hispanic ethnicity; participant age; dog(s), cat(s), cockroaches, and/or smoker(s) in the home; and carpeted floors. CONCLUSIONS: In this U.S. nationwide representative sample, higher endotoxin exposure was significantly associated with measures of wheeze, with no observed protective effect regardless of sensitization status. PMID- 26258645 TI - The Prediction Predicament: Rethinking Necrotizing Soft Tissue Infections Mortality. AB - BACKGROUND: Our study sought to identify independent risk factors predisposing patients with necrotizing soft tissue infections (NSTIs) to mortality from among laboratory values, demographic data, and microbiologic findings in a small population. To this end, a retrospective review was conducted of the medical records of all patients with NSTI who had been treated at our institution from 2003 to 2012 (n=134). METHODS: Baseline demographics and comorbidities, clinical and laboratory values, hospital course, and the microbiologic characteristics of surgical incision cultures were recorded. Each variable was tested for association with survival status and all associated variables with p<0.15 were included in a logistic regression model to seek factors associated independently with mortality. RESULTS: Surprisingly, no demographic or pre-existing condition proved to be a predictor of mortality. Two laboratory values had an inverse correlation to mortality: High C-reactive protein (CRP) and highest recorded CRP. Of surgical incisions that grew bacteria in culture, 33.6% were polymicrobial. Mortality rates were highest with Enterococcus-containing polymicrobial infections (50%), followed by those containing Pseudomonas (40%), and Streptococcus spp. (27%). Understanding why so many studies across the literature, now including our own, find such disparate results for correlation of NSTI mortality with patient data may lie in the fundamentally dynamic nature of the organisms involved. CONCLUSIONS: This study suggests that no single factor present on admission is a robust predictor of outcome; it is likely that survival in NSTI is predicated upon a complex interaction of multiple host and microbial factors that do not lend themselves to reduction into a simple formula. It is also abundantly clear that the well-established principles of NSTI surgery should continue to be followed in all cases, with an emphasis on early debridement, irrespective of apparent severity of initial presentation. PMID- 26258646 TI - Corticosteroids for Severe Community-Acquired Pneumonia: Time to Change Clinical Practice. PMID- 26258647 TI - Modeling and Understanding Combination pMDI Formulations with Both Dissolved and Suspended Drugs. AB - A simulation model has been established to predict the residual aerodynamic particle size distribution (APSD) of dual-component pressurized metered dose inhalers (pMDIs). More specifically, this model estimates the APSD of pMDI formulations containing dissolved and suspended compounds for various formulations, and has been verified experimentally. Simulated and experimental data illustrate that APSDs of the dissolved and suspended components of the pMDI are influenced by concentrations of the dissolved and micronized suspended drugs, along with suspended drug size. Atomized droplets from such combination formulations may contain varying number of suspended drug particles and a representative concentration of dissolved drug. These sub-populations of atomized droplets may explain the residual APSDs. The suspended drug follows a monomodal, lognormal distribution and is more greatly impacted by the size and concentration of the suspended drug in comparison to the concentration of dissolved drug. On the other hand, dissolved drug illustrates a bimodal, lognormal residual particle size distribution both theoretically and experimentally. The smaller mode consists of residual particles made of dissolved drug only, while the larger mode consists of residual particles that contain both dissolved and suspended drugs. The model effectively predicted the size distributions of both the dissolved and suspended components of combination formulations (r(2) value of 0.914 for the comparison of simulated versus experimental MMAD values for the formulations examined). The results demonstrate that this model is a useful tool that may be able to expedite the development of combination pMDI formulation. PMID- 26258648 TI - Decoy Database Improvement for Protein Folding. AB - Predicting protein structures and simulating protein folding are two of the most important problems in computational biology today. Simulation methods rely on a scoring function to distinguish the native structure (the most energetically stable) from non-native structures. Decoy databases are collections of non-native structures used to test and verify these functions. We present a method to evaluate and improve the quality of decoy databases by adding novel structures and removing redundant structures. We test our approach on 20 different decoy databases of varying size and type and show significant improvement across a variety of metrics. We also test our improved databases on two popular modern scoring functions and show that for most cases they contain a greater or equal number of native-like structures than the original databases, thereby producing a more rigorous database for testing scoring functions. PMID- 26258649 TI - Formation of Novel Aqueous Two-Phase Systems with Piperazinium-Based Ionic Liquids and Anionic Surfactants: Phase Behavior and Microstructure. AB - Two novel aqueous two-phase systems (ATPSs) involving protic piperazinium-based ionic liquids (ILs) and anionic surfactants were found in the 1-ethylpiperazinium tetrafluoroborate ([C2pi][BF4]) + sodium dodecyl sulfate (SDS) + H2O system and the 1-phenylpiperazinium tetrafluoroborate ([Phpi][BF4]) + sodium dodecyl benzenesulfonate (SDBS) + H2O system. The ATPS regions in the ternary phase diagrams were determined, and the compositions and the microstructures of the conjugated phases were analyzed by UV-vis, (1)H NMR, DLS, and cryogenic TEM measurements. The results demonstrate size-enhanced micelles for both ATPSs. The strong electrostatic interactions between the cationic moiety of IL and the anionic surfactant play a very important role in the assembly of the large aggregates, and the cation-pi interactions are involved in the [Phpi][BF4] + SDBS + H2O ATPS. In addition, the small cationic moiety of [C2pi][BF4] can be packed in the micelles, while the larger hydrophilic cationic moiety of [Phpi][BF4] makes it difficult to get into the micelles, leading to the different size enhancement effects. The driving force of phase separation is the formation and distribution of the large aggregates in the aqueous solutions. This work presents a novel nonaromatic ATPS formed by a piperazinium-based IL and an anionic surfactant, in which considerable size enhancement of aggregates takes place without the assistance of aromaticity in contrast to the other aromatic ATPSs. PMID- 26258650 TI - Dysregulation of the Transforming Growth Factor beta Pathway in Induced Pluripotent Stem Cells Generated from Patients with Diamond Blackfan Anemia. AB - Diamond Blackfan Anemia (DBA) is an inherited bone marrow failure syndrome with clinical features of red cell aplasia and variable developmental abnormalities. Most affected patients have heterozygous loss of function mutations in ribosomal protein genes but the pathogenic mechanism is still unknown. We generated induced pluripotent stem cells from DBA patients carrying RPS19 or RPL5 mutations. Transcriptome analysis revealed the striking dysregulation of the transforming growth factor beta (TGFbeta) signaling pathway in DBA lines. Expression of TGFbeta target genes, such as TGFBI, BAMBI, COL3A1 and SERPINE1 was significantly increased in the DBA iPSCs. We quantified intermediates in canonical and non canonical TGFbeta pathways and observed a significant increase in the levels of the non-canonical pathway mediator p-JNK in the DBA iPSCs. Moreover, when the mutant cells were corrected by ectopic expression of WT RPS19 or RPL5, levels of p-JNK returned to normal. Surprisingly, nuclear levels of SMAD4, a mediator of canonical TGFbeta signaling, were decreased in DBA cells due to increased proteolytic turnover. We also observed the up-regulation of TGFbeta1R, TGFbeta2, CDKN1A and SERPINE1 mRNA, and the significant decrease of GATA1 mRNA in the primitive multilineage progenitors. In summary our observations identify for the first time a dysregulation of the TGFbeta pathway in the pathobiology of DBA. PMID- 26258651 TI - An electro-conductive fluid as a responsive implant for the controlled stimuli release of diclofenac sodium. AB - The purpose of this study was to develop an electro-responsive co-polymeric (ERP) implantable gel from polyethylene glycol (PEG), sodium polystyrene sulphonate (NaPss), polyvinyl alcohol (PVA), and diethyl acetomidomalonate (DAA) for electro liberation of the model drug diclofenac sodium. Various physicochemical and physicomechanical characterization tests were undertaken on the synthesized drug free gel (ERP G1) and drug-loaded gel (ERP G2). The ability of the gel to release diclofenac sodium following electrical stimulation was evaluated using a galvanostat while Molecular Mechanics (MM) simulations were performed to elucidate the experimental mechanisms. A stable electro-active gel exhibiting superior cycling stability was produced with desirable rheological properties, rigidity (BHN = 35.4 N +/- 0.33 N/mm2; resilience = 10.91 +/- 0.11%), thermal properties (Tg ~ 70 degrees C; Tc ~ 200 degrees C) and homogeneous morphology. "ON-OFF" pursatile gradual drug release (37-94% from t30 min-t180 min) kinetics was observed upon applying electric stimulation intermittently, indicating that drug release from the gel was electrically controlled. Overall, the galvanometric and MM evaluation ascertained the suitability of the PEG/NaPss/PVA ERP-Gel for application as a subcutaneously injectable drug delivery implant. PMID- 26258652 TI - Tlx3 promotes glutamatergic neuronal subtype specification through direct interactions with the chromatin modifier CBP. AB - Nervous system development relies on the generation of precise numbers of excitatory and inhibitory neurons. The homeodomain transcription factor, T-cell leukemia 3 (Tlx3), functions as the master neuronal fate regulator by instructively promoting the specification of glutamatergic excitatory neurons and suppressing the specification of gamma-aminobutyric acid (GABAergic) neurons. However, how Tlx3 promotes glutamatergic neuronal subtype specification is poorly understood. In this study, we found that Tlx3 directly interacts with the epigenetic co-activator cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB)-binding protein (CBP) and that the Tlx3 homeodomain is essential for this interaction. The interaction between Tlx3 and CBP was enhanced by the three amino acid loop extension (TALE)-class homeodomain transcription factor, pre-B-cell leukemia transcription factor 3 (Pbx3). Using mouse embryonic stem (ES) cells stably expressing Tlx3, we found that the interaction between Tlx3 and CBP became detectable only after these Tlx3-expressing ES cells were committed to a neural lineage, which coincided with increased Pbx3 expression during neural differentiation from ES cells. Forced expression of mutated Tlx3 lacking the homeodomain in ES cells undergoing neural differentiation resulted in significantly reduced expression of glutamatergic neuronal subtype markers, but had little effect on the expression on pan neural markers. Collectively, our results strongly suggest that functional interplay between Tlx3 and CBP plays a critical role in neuronal subtype specification, providing novel insights into the epigenetic regulatory mechanism that modulates the transcriptional efficacy of a selective set of neuronal subtype-specific genes during differentiation. PMID- 26258654 TI - Multicolor Depth-Resolved Cathodoluminescence from Eu-Doped SiOC Thin Films. AB - A very bright room-temperature cathodoluminescence (CL) signal, tunable in the visible range by changing the Eu(2+) concentration, has been observed in Eu-doped SiOC films. Depth-resolved CL measurements demonstrate that a bilayer consisting of two SiOC films containing different Eu concentrations allows the continuous tuning of the Eu(2+) emission from blue to green by changing the energy of the exciting electrons. Furthermore, the proper control at the nanoscale of the electron penetration depth allows to obtain a high-quality white light emission. The compatibility of SiOC films with Si technology opens the way to promising applications of Eu-based materials in lighting and display technologies. PMID- 26258653 TI - Corpus Callosum Diffusion and Language Lateralization in Patients with Brain Tumors: A DTI and fMRI Study. AB - BACKGROUND AND PURPOSE: Examining how left-hemisphere brain tumors might impact both the microstructure of the corpus callosum (CC) as measured by fractional anisotropy (FA) values in diffusion tensor imaging (DTI) as well as cortical language lateralization measured with functional MRI (fMRI). METHODS: fMRI tasks (phonemic fluency and verb generation) were performed in order to detect activation in Broca's and Wernicke's area. Twenty patients with left-hemisphere brain tumors were investigated. fMRI results were divided into left dominant (LD), right dominant (RD), or codominant (CD) for language function. DTI was performed to generate FA maps in the anterior and posterior CC. FA values were correlated with the degree of language dominance. RESULTS: Patients who were LD or RD for language in Broca's area had lower FA in the anterior CC than those who were CD for language (median for CD = .72, LD = .66, RD = .65, P < .09). Lateralized versus CD group level analysis also showed that CD patients had higher FA in the anterior CC than patients who displayed strong lateralization in either hemisphere (median for CD = .72, lateralized = .65, P < .05). CONCLUSION: Our preliminary observations indicate that the greater FA in CD patients may reflect a more directional microstructure for the CC in this region, suggesting a greater need for interhemispheric transfer of information. Because brain tumors can cause compensatory codominance, our findings may suggest a mechanism by which interhemispheric transfer is facilitated during plasticity in the presence of a tumor. PMID- 26258655 TI - Dexmedetomidine added to an opioid-based analgesic regimen for the prevention of postoperative nausea and vomiting in highly susceptible patients: A randomised controlled trial. AB - BACKGROUND: Dexmedetomidine, an alpha2 adrenergic receptor agonist, has analgesic, sedative and sympatholytic properties, with a lack of respiratory depression. It is licensed only for intensive care sedation. OBJECTIVE: The objective of this study is to investigate whether intravenous (i.v.) patient controlled analgesia (PCA) with dexmedetomidine added to a fentanyl-based drug mixture could reduce postoperative nausea and vomiting (PONV) in highly susceptible patients undergoing lumbar spinal surgery. DESIGN: A randomised, double-blinded study. SETTING: At a tertiary university hospital between September 2012 and September 2013. PATIENTS: One hundred and eight patients undergoing level 1 or 2 posterior lumbar spinal fusion who had at least three risk factors for PONV (female, nonsmoker, use of postoperative opioids) were randomised into two groups. Three patients were excluded from analysis and 105 patients completed the study. METHODS: Patients received either dexmedetomidine 0.5 MUg kg-1 i.v. (dexmedetomidine group) or 0.9% normal saline (control group) 30 min before the completion of surgery followed by fentanyl 0.5 MUg kg-1 and 4 mg ondansetron. Postoperatively, the PCA (fentanyl 10 MUg kg-1 with 120 mg ketorolac, with or without dexmedetomidine 10 MUg kg-1 made up to a total volume of 100 ml) was programmed to deliver 1 ml bolus (lockout 15 min) with a continuous background infusion of 2 ml h-1. The PCA was used for the first 48 h postoperatively. MAIN OUTCOME MEASURES: The incidence and severity of PONV, cumulative dose of PCA fentanyl consumed and pain scores were assessed for 48 h. RESULTS: The dexmedetomidine group experienced less nausea during the time interval 1 to 3 h postoperatively compared with the control group [odds ratio (OR) 0.32; 95% confidence interval (CI) 0.13 to 0.77; P = 0.019]. The intensity of nausea between the groups during the first 48 h was comparable, but the dexmedetomidine group had a lower incidence of moderate to severe nausea (OR 0.28; 95% CI 0.12 to 0.67; P < 0.003). Pain scores were not significantly different between the groups, but patients in the dexmedetomidine group required less fentanyl and less rescue analgesia in the first 12 h. Compared with the control group, patients in the dexmedetomidine group experienced almost twice as many episodes of hypotension and bradycardia, but this failed to reach statistical significance. CONCLUSION: Adding dexmedetomidine to a fentanyl-based PCA drug mixture reduces the frequency and severity of acute postoperative nausea in highly susceptible patients. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01840254. PMID- 26258656 TI - Persistent posthysterectomy pain: A prospective, observational study. AB - BACKGROUND: There is a large variation in the prevalence of persistent postsurgical pain depending on the type of surgery. It is unclear how common persistent postsurgical pain is after vaginal or laparoscopic hysterectomy. OBJECTIVES: The objective of this study was to define the prevalence of persistent postsurgical pain 6 months after laparoscopic or vaginal hysterectomy for benign causes and to ascertain the intensity of the pain and its possible predictors. DESING: A prospective, observational study. SETTING: Pirkanmaa Hospital District between October 2008 and September 2013. PATIENTS: Two hundred and forty-two women who underwent laparoscopic (150) or vaginal (92) hysterectomy for benign causes and who also participated in our earlier studies concerning acute pain. INTERVENTIONS: A pain questionnaire and a prestamped return envelope were mailed to all women 6 months after surgery. If the questionnaire had not been returned within 4 weeks, a reminder was sent. Data regarding preoperative pain and acute postoperative pain were collected from the records of our earlier studies concerning acute pain. The patient characteristics and surgical outcomes were collected from the patients' medical records. MAIN OUTCOME MEASURE: The prevalence of persistent postsurgical pain 6 months after hysterectomy. RESULTS: The response rate was 94% (227 respondents). Twenty-seven (18.9%) of 143 patients who had no pain preoperatively had persistent pain after surgery. Overall, 26.0% of patients had persistent pelvic pain 6 months after surgery. On an 11-point numeric rating scale (NRS), most of the patients rated their average pain as mild (NRS 0 to 3) and only 6.9% rated their worst pain as severe (NRS 7 to 10). Smoking, acute postoperative pain at 4 h after surgery and a laparoscopic approach were significantly associated with persistent pain in a multivariable analysis. CONCLUSION: Persistent posthysterectomy pain is common, but pain is mild and does not interfere with daily activities for most of the patients 6 months after surgery. Smoking is the strongest predictor for persistent pain. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT 01537731. PMID- 26258657 TI - Assessment of haemostasis in patients with cirrhosis: Relevance of the ROTEM tests?: A prospective, cross-sectional study. AB - BACKGROUND: In patients with cirrhosis, decreased rotational thromboelastometry (ROTEM) parameters suggest hypocoagulability secondary to liver dysfunction. However, observed normal or increased thrombin generation suggests preserved haemostasis and/or a procoagulant state. The correlated levels of both coagulation factors and inhibitors also support preserved haemostasis. OBJECTIVE: The objective of this study is to investigate the correlation between three specific approaches of haemostasis (ROTEM, thrombin generation and coagulation factors/inhibitors) on the same plasma sample from patients with cirrhosis. DESIGN: A prospective, observational study. SETTING: Single university hospital. PARTICIPANTS: Forty patients with cirrhosis. INTERVENTION: Measurement of the following factors: model for end-stage liver disease (MELD) scores; ROTEM maximum clot firmness (ROTEM-MCF) in EXTEM, INTEM, FIBTEM assays; fibrinogen; factors V and VIII; von Willebrand factor; protein C; protein S; antithrombin; and the thrombin generation test (TGT) enabling the calculation of endogenous thrombin potential without and with thrombomodulin, and the ratio of endogenous thrombin potential with-to-without thrombomodulin (regarded as an index of hypercoagulability). RESULTS: ROTEM-MCF values were distributed within the normal and hypocoagulation ranges; were correlated to variations in factor V, fibrinogen, protein C and S and antithrombin; and were inversely correlated to MELD scores (rho > 0.5; P < 0.05). Levels of von Willebrand factor were above normal and were not correlated with any other factor levels. After addition of thrombomodulin, endogenous thrombin potential values were distributed within or above normal values. Factor V variation was correlated to the ratio of endogenous thrombin potential with-to-without thrombomodulin. CONCLUSION: ROTEM indicated hypocoagulability correlated to liver dysfunction. In contrast, the TGT indicated a preserved or even increased coagulation profile (which was supported by the correlation between coagulant factors and inhibitors) and a potential for hypercoagulability inversely correlated to the degree of liver dysfunction. ROTEM may not be appropriate for haemostasis assessment in patients with liver cirrhosis and could lead to the unnecessary transfusion of fresh frozen plasma. TRIAL REGISTRATION: S.C. 3024 - ID RCB: 2012-A01728-35. PMID- 26258659 TI - The minimum clinically important difference is fundamental to all clinical trials. PMID- 26258658 TI - Effective tranexamic acid concentration for 95% inhibition of tissue-type plasminogen activator induced hyperfibrinolysis in children with congenital heart disease: A prospective, controlled, in-vitro study. AB - BACKGROUND: Although recent studies have assessed tranexamic acid (TXA) pharmacokinetics in different subgroups, the effective concentration of TXA required to completely inhibit fibrinolysis remains to be determined. OBJECTIVE: An in-vitro determination of the effective TXA concentration needed for 95% inhibition (EC95) of tissue-type plasminogen activator (t-PA) activated fibrinolysis, using an experimental model designed for thromboelastometry (ROTEM). DESIGN: A prospective interventional study. SETTING: Department of Anaesthesiology, Queen Fabiola Children's University Hospital and Laboratory of Haematology and Haemostasis, Brugmann University Hospital. Patients were enrolled between June 2013 and October 2014. PATIENTS AND VOLUNTEERS: Twenty children, aged between 1 and 10 years, undergoing elective cardiac catheterisation were included (10 with cyanotic and 10 with noncyanotic diseases). Exclusion criteria were child requiring a procedure in a moribund state. Ten adult volunteers were also included as controls. INTERVENTION: Citrated whole blood samples were obtained from children and volunteers. MAIN OUTCOMES MEASURES: The extrinsic coagulation pathway was activated by tissue factor using the EXTEM test on ROTEM. The degree of lysis measured 30 min (LI30) after the clotting time (CT), and clot amplitudes measured at different times were recorded at baseline, after addition of 1535 units t-PA ml(-1), and following the addition of increasing TXA concentrations in t-PA activated samples. RESULTS: The concentration-effect analysis performed with lysis index after 30 min (LI30) allowed the determination of TXA efficacy concentration 50% (EC50), and calculation of the EC95, which was significantly lower in cardiac surgery children than in adults [8.6 MUg ml(-1); 95% confidence interval (95% CI) 6.9 to 14.9 versus 11.3 MUg ml(-1); 95% CI 10.6 to 12.9, P < 0.001]. CONCLUSION: In this in-vitro study, we observed that the EC95 TXA concentration that completely inhibited t-PA induced hyperfibrinolysis in children with congenital heart was significantly lower than the concentration required in healthy adult volunteers. Further studies are needed to confirm that this plasma concentration can effectively inhibit fibrinolysis activation in children undergoing cardiac surgery. PMID- 26258660 TI - Dendron-Mediated Engineering of Interparticle Separation and Self-Assembly in Dendronized Gold Nanoparticles Superlattices. AB - Self-assembly of nanoparticles into designed structures with controlled interparticle separations is of crucial importance for the engineering of new materials with tunable functions and for the subsequent bottom-up fabrication of functional devices. In this study, a series of lipophilic, highly flexible, disulfide dendritic wedges (generations 0-4), based on 2,2 bis(hydroxymethyl)propionic acid, was designed to bind Au nanoparticles with a thiolate bond. By controlling the solvent evaporation rate, the corresponding dendron-capped Au hybrids were found to self-organize into hexagonal close-packed (hcp) superlattices. The interparticular spacing was progressively varied from 2.2 to 6.3 nm with increasing dendritic generation, covering a range that is intermediate between commercial ligands and DNA-based ligand shells. Dual mixtures made from some of these dendronized hybrids (i.e., same inner core size but different dendritic covering) yielded binary superlattice structures of unprecedented single inorganic components, which are isostructural with NaZn13 and CaCu5 crystals. PMID- 26258661 TI - Pressure-Modulated Conductivity, Carrier Density, and Mobility of Multilayered Tungsten Disulfide. AB - Tungsten disulfide (WS2) is a layered transition metal dichalcogenide (TMD) that differs from other two-dimensional (2D) compounds such as graphene due to its unique semiconducting, tunable-band-gap nature. Multilayered WS2 exhibits an indirect band gap Eg of ~1.3 eV, along with a higher load-bearing ability that is promising for strain-tuning device applications, but the electronic properties of multilayered WS2 at higher strain conditions (i.e., static strain >12%) remain an open question. Here we have studied the structural, electronic, electrical, and vibrational properties of multilayered WS2 at hydrostatic pressures up to ~35 GPa experimentally in a diamond anvil cell and theoretically using first-principles ab initio calculations. Our results show that WS2 undergoes an isostructural semiconductor-to-metallic (S-M) transition at approximately 22 GPa at 280 K, which arises from the overlap of the highest valence and lowest conduction bands. The S-M transition is caused by increased sulfur-sulfur interactions as the interlayer spacing decreases with applied hydrostatic pressure. The metalization in WS2 can be alternatively interpreted as a 2D to 3D (three-dimensional) phase transition that is associated with a substantial modulation of the charge carrier characteristics including a 6-order decrease in resistivity, a 2-order decrease in mobility, and a 4-order increase in carrier concentration. These distinct pressure-tunable characteristics of the dimensionalized WS2 differentiate it from other TMD compounds such as MoS2 and promise future developments in strain modulated advanced devices. PMID- 26258662 TI - Prospective diagnostic test accuracy comparison of computed tomography during arterial portography and Primovist magnetic resonance imaging in the pre operative assessment of colorectal cancer liver metastases. AB - OBJECTIVES: To assess and compare the accuracy and inter-observer agreement for the detection of liver lesions using Primovist magnetic resonance imaging (pMRI) and computed tomography during arterial portography (CTAP). METHODS: Patients evaluated at St George Hospital Liver Unit for colorectal liver metastases (CRCLM) underwent CTAP as part of standard staging. pMRI was added to the pre operative assessment. Two radiologists reported CTAP and two reported pMRI. The sensitivity and specificity of CTAP and pMRI were calculated using histopathology as the gold standard. RESULTS: Complete data were available for 62 patients corresponding to 219 lesions confirmed on histopathology. Agreement on the detection of lesions between the two radiologists that reported pMRI was higher than for CTAP (Kappa = 0.80 versus 0.74). Specificity of lesion detection for pMRI was 0.88 and 0.83 for CTAP (P = 0.112). Sensitivity for pMRI was 0.83 and 0.81 for CTAP. For patients who had chemotherapy before evaluation, pMRI had a significantly higher specificity than CTAP (0.79 versus 0.63, P = 0.011). CONCLUSIONS: pMRI is less invasive, has a good inter-observer agreement, has comparable sensitivity and specificity to CTAP in the pre-chemotherapy population and demonstrates better specificity in patients assessed post-chemotherapy. pMRI is a valid alternative to CTAP in the assessment of CRCLM. PMID- 26258663 TI - Measuring the cost-effectiveness of midwife-led versus physician-led intrapartum teams in developing countries. AB - International agencies have advocated scaling-up of midwifery resources as an important method for improving maternal health and reducing maternal mortality rates (MMR). The cost-effectiveness of midwife-led versus physician-led intrapartum care is an important consideration in the human resource planning required to reduce MMR. Studies suggest that midwife-led teams can achieve comparable effectiveness and outcomes using less medically intensive care compared with physician-led teams. In the absence of adequate medical cost data, decision makers should consider the substantially lower average costs for three main drivers: salaries, benefits and incentives (>=two-times lower); preservice training (three-times lower) and attrition (two-times lower) necessary to deliver intrapartum care at the level of midwife competencies. This suggests that scale up of midwifery resources is a less expensive and more cost-effective way to reduce MMRs and could potentially increase access to skilled intrapartum care. PMID- 26258664 TI - Memantine Augmentation in a Down's Syndrome Adolescent with Treatment- Resistant Obsessive-Compulsive Disorder. PMID- 26258665 TI - Dyskeratosis of the Face: A Quiz. PMID- 26258666 TI - Resistance to Inhibitors of Cholinesterase 3 (Ric-3) Expression Promotes Selective Protein Associations with the Human alpha7-Nicotinic Acetylcholine Receptor Interactome. AB - The alpha7-nicotinic acetylcholine receptor (alpha7-nAChR) is a ligand-gated ion channel widely expressed in vertebrates and is associated with numerous physiological functions. As transmembrane ion channels, alpha7-nAChRs need to be expressed on the surface of the plasma membrane to function. The receptor has been reported to associate with proteins involved with receptor biogenesis, modulation of receptor properties, as well as intracellular signaling cascades and some of these associated proteins may affect surface expression of alpha7 nAChRs. The putative chaperone resistance to inhibitors of cholinesterase 3 (Ric 3) has been reported to interact with, and enhance the surface expression of, alpha7-nAChRs. In this study, we identified proteins that associate with alpha7 nAChRs when Ric-3 is expressed. Using alpha-bungarotoxin (alpha-bgtx), we isolated and compared alpha7-nAChR-associated proteins from two stably transfected, human tumor-derived cell lines: SH-EP1-halpha7 expressing human alpha7-nAChRs and the same cell line further transfected to express Ric-3, SH-EP1 halpha7-Ric-3. Mass spectrometric analysis of peptides identified thirty-nine proteins that are associated with alpha7-nAChRs only when Ric-3 was expressed. Significantly, and consistent with reports of Ric-3 function in the literature, several of the identified proteins are involved in biological processes that may affect nAChR surface expression such as post-translational processing of proteins, protein trafficking, and protein transport. Additionally, proteins affecting the cell cycle, the cytoskeleton, stress responses, as well as cyclic AMP- and inositol triphosphate-dependent signaling cascades were identified. These results illuminate how alpha-bgtx may be used to isolate and identify alpha7-nAChRs as well as how the expression of chaperones such as Ric-3 can influence proteins associating with alpha7-nAChRs. These associating proteins may alter activities of alpha7-nAChRs to expand their functionally-relevant repertoire as well as to affect biogenesis and membrane trafficking of alpha7 nAChRs. PMID- 26258667 TI - MADS-box transcription factor OsMADS25 regulates root development through affection of nitrate accumulation in rice. AB - MADS-box transcription factors are vital regulators participating in plant growth and development process and the functions of most of them are still unknown. ANR1 was reported to play a key role in controlling lateral root development through nitrate signal in Arabidopsis. OsMADS25 is one of five ANR1-like genes in Oryza Sativa and belongs to the ANR1 clade. Here we have investigated the role of OsMADS25 in the plant's responses to external nitrate in Oryza Sativa. Our results showed that OsMADS25 protein was found in the nucleus as well as in the cytoplasm. Over-expression of OsMADS25 significantly promoted lateral and primary root growth as well as shoot growth in a nitrate-dependent manner in Arabidopsis. OsMADS25 overexpression in transgenic rice resulted in significantly increased primary root length, lateral root number, lateral root length and shoot fresh weight in the presence of nitrate. Down-regulation of OsMADS25 in transgenic rice exhibited significantly reduced shoot and root growth in the presence of nitrate. Furthermore, over-expression of OsMADS25 in transgenic rice promoted nitrate accumulation and significantly increased the expressions of nitrate transporter genes at high rates of nitrate supply while down-regulation of OsMADS25 produced the opposite effect. Taken together, our findings suggest that OsMADS25 is a positive regulator control lateral and primary root development in rice. PMID- 26258668 TI - Efficacy and safety of eltrombopag in treatment-refractory primary immune thrombocytopenia: a retrospective study. AB - Eltrombopag was used in patients with chronic primary immune thrombocytopenia (ITP) who did not tolerate or were refractory to two or more previous treatments. The primary aims of the study were to determine the efficacy and safety of long term eltrombopag treatment. Data were extracted from medical chart records retrospectively. Platelet count of at least 50 000/MUl at any time point during the treatment was defined as the 'response'. Median duration of eltrombopag treatment was 29 weeks (11-74). The number of patients who had a platelet count of at least 50 000/MUl at any time point was 26 (83.9%). The response was achieved by the second week in most of the patients. Concomitant ITP medications were withdrawn in nine out of the 11 patients. Eltrombopag was discontinued in one patient due to sustained response despite discontinuation of the treatment. Age, sex, concomitant ITP treatments, and previous ITP treatment failures had no impact on the treatment response. The treatment was discontinued due to thrombosis in only four patients. Four patients experienced a minor bleeding event. Hepatotoxicity and all other adverse events were mild and manageable. Eltrombopag is effective, safe, and well tolerated in the long-term treatment of chronic ITP patients. PMID- 26258669 TI - Two consecutive pregnancies in a patient with paroxysmal nocturnal haemoglobinuria treated with anticoagulant therapy at different doses. AB - Paroxysmal nocturnal haemoglobinuria (PNH) is a rare acquired disorder of haematopoietic stem cells characterized by intravascular haemolysis, cytopenias and thrombophilia. Thrombophilia is the leading cause of mortality in patients with PNH. As the risk of thrombogenesis further increases during pregnancy and the postpartum period, an anticoagulant therapy is generally recommended for pregnant women with PNH. However, there are no standardized criteria for determining the appropriate dose of anticoagulant therapy. We describe the case of a PNH patient with who was managed with anticoagulant therapy at different doses during two consecutive pregnancies. A prophylactic dose of heparin was administered during her first pregnancy and a therapeutic dose, during her second pregnancy. Both pregnancies resulted in uncomplicated vaginal deliveries without thrombosis. Interestingly, not only D-dimer (as a thrombotic marker) but also lactate dehydrogenase (as a haemolytic marker) levels were lower during her second pregnancy when a therapeutic dose of heparin was used. PMID- 26258670 TI - Measuring dabigatran with the dilute Russell viper venom confirm assay in an anticoagulation clinic population. AB - The dabigatran dose-response is predictable; however, it is necessary to measure plasma levels in a variety of clinical conditions. We evaluated a novel dabigatran measure - the 'dilute Russell viper venom confirm (DRVVC) assay' - against current developmental assays and a reference method. We measured plasma dabigatran and compared results from the Stago Sta-Clot DRVVC assay, Stago Ecarin Chromogenic Assay, Biophen Hemoclot Thrombin Inhibitor, and liquid chromatography tandem mass spectrometry. We obtained dabigatran calibrators and controls from Biophen, and performed the coagulation assays using a Stago STA-R Evolution coagulometer. Liquid chromatography tandem mass spectrometry method specimens were performed on an AB Sciex instrument at LabCorp. We enrolled 97 anticoagulation clinic patients (mean age 76 years) who were taking 150 mg dabigatran twice daily. All had creatinine clearances above 30 ml/min; patients were not excluded for concurrent medications or health issues. Citrated blood specimens were processed immediately, and stored at -70 degrees C. We did not correlate collection time with medication time. We employed descriptive statistics, analysis of variance, and the Bland-Altman difference plot to assess the data. The range for all assays was 11.6-917 ng/ml. Analysis of variance generated a P value of 0.1 and Bland-Altman differences were all below 4.0% compared with DRVVC. The DRVVC measures dabigatran with validity comparable to other methods. PMID- 26258671 TI - Changes in thrombin generation in children after cardiac surgery and ex-vivo response to blood products and haemostatic agents. AB - Impaired haemostasis has been reported in children with congenital heart disease undergoing cardiopulmonary bypass. As thrombin generation encompasses all phases of the coagulation process, this analysis might provide the best assessment of global haemostasis. A prospective study was undertaken to test the hypothesis that thrombin generation reveals an impaired haemostasis after paediatric cardiac surgery and that ex-vivo addition of platelet concentrate and haemostatic agents improves thrombin generation. The study comprised 29 children with congenital heart disease, who underwent corrective surgery including cardiopulmonary bypass. Thrombin generation was analysed both in platelet-poor plasma and platelet-rich plasma. Analysis of the thrombin generation showed a significantly prolonged lag time (Pplatelet-poorandplatelet-richplasma < 0.001), decreased peak thrombin generation (Pplatelet-poorplasma = 0.013; Pplatelet-richplasma < 0.001) as well as a decreased endogenous thrombin generation potential (Pplatelet poorandplatelet-richplasma < 0.001) after cardiopulmonary bypass compared to baseline. Ex-vivo addition of platelet concentrate, fibrinogen concentrate and recombinant factor VIIa improved thrombin generation significantly (all P < 0.001). Changes were most pronounced after addition of platelet concentrate. The present study showed that thrombin generation was significantly reduced after cardiopulmonary bypass in children, both when analysed in platelet-poor and platelet-rich plasma. The impaired haemostasis was not only restored after ex vivo addition of platelet concentrate but also rVIIa improved the haemostatic capacity. PMID- 26258672 TI - Novel hematologic inflammatory parameters to predict acute mesenteric ischemia. AB - Acute mesenteric ischaemia (AMI) is an emergency condition that requires urgent diagnosis. Neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) have been studied as inflammatory biomarkers in atherosclerosis, but data regarding AMI are lacking. The study population included patients with AMI (n = 46) versus age and sex-matched healthy controls (n = 46). Computed multidetector tomographic angiography was performed to diagnose AMI. NLR and PLR were calculated using complete blood count. C-reactive protein (CRP) levels were also analyzed. Neutrophil levels and lymphocytes were significantly higher in patients with AMI than in the control individuals (P < 0.001 and P = 0.43, respectively). NLR levels were significantly higher in patients with AMI compared with that in the control individuals (P < 0.001). Platelet levels did not reach statistical significance between the groups (P = 0.709). However, patients with AMI had significantly higher PLR levels than the control group (P = 0.039). CRP levels on admission were higher in patients with AMI in comparison with control individuals. There was also a positive correlation between NLR and CRP (r = 0.548, P < 0.001), and between PLR and CRP (r = 0.528, P < 0.001). NLR level greater than 4.5, measured on admission, yielded an area under the curve value of 0.790 (95% confidence interval 0.681-0.799, sensitivity 77%, specificity 72%), and PLR level of greater than 157 yielded an area under the curve value of 0.604 (95% confidence interval 0.486-0.722, sensitivity 59%, specificity 65%). Patients with AMI had increased NLR, PLR, and CRP levels compared with controls. Increased NLR and PLR was an independent predictor of AMI. PMID- 26258673 TI - Rivaroxaban and apixaban in orthopaedics: is there a difference in their plasma concentrations and anticoagulant effects? AB - The aim of this study was to improve knowledge of what happens in the coagulation of orthopaedic patients under rivaroxaban and apixaban, in order to finalize and cross-validate effective measurement methods and to provide arguments for helping to reference one or the other drug in our central pharmacy. One hundred and two patients undergoing total hip or knee replacement were included. Half of them received rivaroxaban and the other half received apixaban. Blood samples (n = 244 with each drug) were taken at Cmax preoperatively and twice a week, apart from the day of the patient's discharge, when Ctrough concentration was targeted. Routine coagulation parameters, and functional and liquid chromatography tandem mass spectrometry assays for measurement of circulating concentrations were studied. The LC-MS/MS assay and the functional assays carried out in patients under routine conditions were highly correlated, apart from low concentrations (<30 ng/ml), which were affected by the variable individual potential to inhibit the exogenous bovine Xa used in the functional assays. After 1 week of treatment, the drugs differed: Cmax and Ctrough were closer when apixaban was taken twice daily (83 +/- 39 and 58 +/- 17 ng/ml) than with rivaroxaban taken once a day (113 +/- 67 and 13 +/- 20 ng/ml). Rivaroxaban had a greater influence on routine coagulation tests and reduced the maximum thrombin concentration more efficiently, as assessed by the thrombin generation test. Although rivaroxaban and apixaban present apparently similar constant rates, they exhibit significant differences in their concentrations and anticoagulant effects when studied ex vivo in orthopedic patients. PMID- 26258674 TI - Meta-analysis on efficacy and safety of new oral anticoagulants for venous thromboembolism prophylaxis in elderly elective postarthroplasty patients. AB - The risk of venous thromboembolism (VTE) increases with age. New oral anticoagulants (NOACs) have been increasingly studied for VTE prophylaxis in patients with elective postarthroplasty. Although the elderly population accounts for a significant proportion of patients requiring VTE prophylaxis, safety and efficacy of NOACs in this subgroup for VTE prophylaxis has not been well studied. Relevant studies were identified through electronic literature searches of MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov (from inception to 12 August 2014). Phase III randomized controlled trials that compared NOACs against low-molecular-weight heparin (LMWH) in the prevention of VTE prophylaxis in patients with elective postarthroplasty were included. We defined our elderly population as adults of at least 75 years and assessed the reported safety and efficacy outcomes with NOACs in this population. Study-specific odds ratios (ORs) were calculated and between-study heterogeneity was assessed using the I statistic. In nine trials involving 29 403 patients, the risk of VTE or VTE related deaths in elderly patients with elective postarthroplasty was similar with NOACs compared with LMWH (OR 0.62, 95% confidence interval 0.30-1.26; P = 0.18; I = 44%) but bleeding risk was significantly lower (OR 0.71, 95% confidence interval 0.53-0.94; P = 0.02; I = 0%). Analysis of individual NOACs showed superior efficacy but similar safety for apixaban when compared with LMWH. Efficacy and safety profiles of rivaroxaban and dabigatran were similar to LMWH. In elderly patients with elective postarthroplasty, NOACs have similar efficacy but superior safety when compared with enoxaparin for VTE prophylaxis. PMID- 26258675 TI - Association of mean platelet volume with impaired myocardial reperfusion and short-term mortality in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. AB - Impaired myocardial reperfusion, defined angiographically by myocardial blush grade (MBG) 0 or 1, is associated with adverse clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to investigate the impact of admission mean platelet volume (MPV) on the myocardial reperfusion and 30-day all-cause mortality in patients with STEMI with successful epicardial reperfusion after primary percutaneous coronary intervention (PCI). A total of 453 patients with STEMI who underwent primary PCI within 12 h of symptoms onset and achieved thrombolysis in myocardial infarction (TIMI) 3 flow at infarct-related artery after PCI were enrolled and divided into two groups based on postinterventional MBG: those with MBG 2/3 and those with MBG 0/1. Admission MPV was measured before coronary angiography. The primary endpoint was all-cause mortality at 30 days. MPV was significantly higher in patients with MBG 0/1 than in patients with MBG 2/3 (10.38 +/- 0.98 vs. 9.59 +/- 0.73, P < 0.001). The cumulative 30-day all-cause mortality rate was significantly higher in the groups with high MPV and MBG 0/1 (6.8 vs. 1.5%, P = 0.005, 7.6 vs. 1.9%, P = 0.006, respectively). Multivariate logistic regression analysis demonstrated MPV was independently associated with postinterventional impaired myocardial reperfusion (odds ratio 2.684, 95% confidence interval 2.010-3.585, P < 0.001) and 30-day all-cause mortality (hazard ratio 1.763, 95% confidence interval 1.009 3.079, P = 0.046). Increased MPV on admission is an independent predictor of impaired myocardial reperfusion and short-term mortality in patients with STEMI with successful epicardial reperfusion after primary PCI. Admission MPV may be additive to conventional risk factors in patients with STEMI undergoing PCI. PMID- 26258676 TI - Neonates born to mothers with immune thrombocytopenic purpura: a single-center experience of 20 years. AB - Neonates born to mothers with immune thrombocytopenic purpura (ITP) have an increased risk of having thrombocytopenia and bleeding. The aim of our study was to determine maternal and fetal factors that can predict bleeding risk in neonates born to mothers with ITP, and effective treatment strategies by retrospective analysis of our single-center data. We performed a retrospective data review of neonates that were recorded as 'neonates born to mothers with ITP' in the Neonatal ICU of Hacettepe University, Ihsan Dogramaci Children's Hospital, Ankara, Turkey. Medical records of 36 neonates born from 35 mothers were analyzed. Among the 36 neonates born to mothers with ITP, thrombocytopenia (platelet count of less than 150 * 10/l) was detected in 20 (56.0%) neonates on the first day of life. Twelve of the 20 neonates with thrombocytopenia (60.0%) required treatment to increase the platelet counts. Clinical findings related to thrombocytopenia occurred in three (15.0%) neonates, but none of them presented with severe bleeding. There was no statistically significant association between neonatal lowest platelet count and maternal lowest platelet count, maternal platelet count at the time of delivery, and duration of thrombocytopenia, respectively. Neonates born to mothers with ITP have an increased tendency to develop thrombocytopenia, but severe bleeding is very rare in these neonates. Clinicians should pay special attention to follow these neonates. According to our results, both intravenous immunoglobulin and methyl prednisolone were found to be in equivalent efficacy for the treatment of neonatal thrombocytopenia due to maternal ITP. PMID- 26258677 TI - Low-dose tertiary prophylactic therapy reduces total number of bleeds and improves the ability to perform activities of daily living in adults with severe haemophilia A: a single-centre experience from Beijing. AB - Full-dose prophylaxis treatment for persons with haemophilia is not affordable in China due to its economic constraints, particularly in adults requiring higher clotting factor (CFC) doses. Low-dose tertiary prophylaxis for adults with severe haemophilia A (SHA) in Beijing became feasible and implemented when government insurance covering 85% CFC cost in Beijing began in December 2009. The aim of this study was to evaluate the benefits of low-dose tertiary prophylaxis in SHA adults. Analysis of data on 33 patients on low-dose tertiary prophylaxis (5-10 IU/kg, two to three times per week) at the Haemophilia Treatment Center, Peking Union Medical College Hospital between December 2009 and December 2013. The 33 patients (age 18-60 years, mean 33.4) were on prophylaxis for 20.8 +/- 9.9 months (compared with prior on-demand therapy for 20.0 +/- 11.7 months). Prophylaxis resulted in significant decrease in annual bleeding rate (ABR, 11.8 +/- 7.6 vs. 41.5 +/- 20.7, 71.1% reduction, P < 0.0001), and significant improvement in Functional Independence Score in Haemophilia (FISH) measurement reflecting improvement in self-care and mobility. Radiologic (Pettersson) joint score was neither improved nor deteriorated. Ten of the 33 patients originally wheel chair and bed-bound began to walk and function independently in their daily lives. Low dose tertiary prophylaxis for adults with SHA in China is feasible and beneficial. Although the average ABR remained high, a significant improvement in self-care and mobility measured by FISH was observed. These promising clinical experiences form the basis for further formal studies with more defined therapeutic protocol and outcome measures for affordable prophylaxis regimens in haemophilia adults in China. PMID- 26258678 TI - The effect of the amiodarone-warfarin interaction on anticoagulation quality in a single, high-quality anticoagulation center. AB - Clinical trials have reported a low time in therapeutic range (TTR) in patients with atrial fibrillation treated with both warfarin andamiodarone. These trials included centers and countries with both high and low TTRs. What is the impact of amiodarone on the TTR in a single, high-quality anticoagulation clinic? TTR was assessed in amiodarone and nonamiodarone-treated patients from a University anticoagulation clinic. Baseline characteristics between patients ever-taking or never-taking amiodarone were similar, except more amiodarone patients were smokers (19.5 vs. 6.1%, P = 0.0031). The TTR calculated from 8901international normalized ratios (INRs) in 249 nonamiodarone patients with a mean follow-up of 34 +/- 20 months (mean INR 36 +/- 18) was 66 +/- 16.6% compared with 61.3 +/- 16.2% (P = 0.111) from 1455 INRs in 41 amiodarone-treated patients with a mean follow-up of 28 +/- 20 months (mean INR 35 +/- 22). Factors associated with a low TTR were male sex (P = 0.0013), smoker (P = 0.0048), and amiodarone use (P = 0.0374). A second on-treatment analysis, in which the TTR was calculated only during amiodarone therapy, resulted in similar findings; however, amiodarone did not emerge as a predictor of a low TTR. In 11 patients, the TTR prior to amiodarone (54.5 +/- 22.2%) was not significantly different in the first 3 months (54.6 +/- 33.4%) or after 3 months (67.2 +/- 33.7%) of amiodarone. In a single high-quality anticoagulation center, anticoagulation quality, as measured by the TTR, can be comparable in amiodarone and nonamiodarone-treated patients. PMID- 26258679 TI - What is the most reliable marker in the differential diagnosis of pulmonary embolism and community-acquired pneumonia? AB - Because of similar clinical manifestations and laboratory findings, differential diagnosis of pulmonary embolism and community-acquired pneumonia (CAP) is generally difficult. Therefore, this study was conducted to find good markers for the easy, cheap, and fast differential diagnosis of pulmonary embolism and CAP. Thirty-four patients diagnosed with pulmonary embolism and 38 patients with CAP who were admitted to either emergency department or chest diseases outpatient clinic were included in this study. On admission and third day, complete blood count, C-reactive protein (CRP), erythrocyte sedimentation rate, procalcitonin (PCT), and D-dimer levels of each patient were measured. Neutrophil-to-lymphocyte ratio (NLR) was calculated using the formula NLR = neutrophil count/lymphocyte count. NLR/D-dimer and PCT/D-dimer ratios were also calculated. First day neutrophil count (P = 0.005), NLR (P = 0.002), CRP (P < 0.001), erythrocyte sedimentation rate (P < 0.001), PCT (P < 0.001), NLR/D-dimer (P < 0.001), and PCT/D-dimer (P < 0.001) levels were higher in patients with CAP compared with patients with pulmonary embolism. In stepwise logistic regression analysis done with all the parameters used for the differential diagnosis of pulmonary embolism and CAP, CRP, PCT/D-dimer, and NLR/D-dimer were found to be independent predictive factors for the presence of CAP. Among these factors, NLR/D-dimer ratio was found to be the most sensitive (97.4%) to have the highest negative predictive value 96.7% and to be the most accurate (area under curve = 0.921) (91.7%) parameter for the differential diagnosis of pulmonary embolism and CAP. In this study, NLR/D-dimer ratio was found to be more sensitive and more selective with negative predictive value and area under curve for the differential diagnosis of pulmonary embolism and CAP compared with other laboratory tests. PMID- 26258680 TI - Elemental Characterization and Discrimination of Nontoxic Ammunition Using Scanning Electron Microscopy with Energy Dispersive X-Ray Analysis and Principal Components Analysis. AB - Concerns over the toxic by-products produced by traditional ammunition have led to an increase in popularity of nontoxic ammunition. In this work, the chemical composition of six brands of nontoxic ammunition was investigated and compared to that of a road flare, which served as an environmental source with similar composition. Five rounds of each brand were fired while a further five were disassembled and the primer alone was fired. Particles collected from all samples, including the road flare, were analyzed by scanning electron microscopy with energy dispersive X-ray analysis. Common elements among the different ammunition brands included aluminum, potassium, silicon, calcium, and strontium. Spectra were then subjected to principal components analysis in which association of the primer to the intact ammunition sample was generally possible, with distinction among brands and from the road flare sample. Further, PCA loadings plots indicated the elements responsible for the association and discrimination observed. PMID- 26258681 TI - An IL-13 promoter polymorphism associated with liver fibrosis in patients with Schistosoma japonicum. AB - The aim of this study was to determine whether two polymorphisms in the gene encoding IL13 previously associated with Schistosoma hematobium (S. hematobium) and S. mansoni infection are associated with S. japonicum infection. Single nucleotide polymorphisms (SNPs) rs1800925 (IL13/-1112C>T) and rs20541 (IL13R130Q) were genotyped in 947 unrelated individuals (307 chronically infected, 339 late stage with liver fibrosis, 301 uninfected controls) from a schistosomiasis endemic area of Hubei province in China. Regression models were used to evaluate allelic and haplotypic associations with chronic and late-stage schistosomiasis adjusted for non-genetic covariates. Expression of IL-13 was measured in S. japonicun-infected liver fibrosis tissue and normal liver tissue from uninfected controls by immunohistochemistry (IHC). The role of rs1800925 in IL-13 transcription was further determined by Luciferase report assay using the recombinant PGL4.17-rs180092 plasmid. We found SNP rs1800925T was associated with late-stage schistosomiasis caused by S. japonicum but not chronic schistosomiasis (OR = 1.39, 95%CI = 1.02-1.91, p = 0.03) and uninfected controls (OR = 1.49, 95%CI = 1.03-2.13, p = 0.03). Moreover, the haplotype rs1800925T-rs20541C increased the risk of disease progression to late-stage schistosomiasis (OR = 1.46, p = 0.035), whereas haplotype rs1800925C-rs20541A showed a protective role against development of late-stage schistosomiasis (F = 0.188, OR = 0.61, p = 0.002). Furthermore, S. japonicum-induced fibrotic liver tissue had higher IL13 expression than normal liver tissue. Plasmid PGL4.17-rs1800925T showed a stronger relative luciferase activity than Plasmid PGL4.17-rs1800925C in 293FT, QSG-7701 and HL-7702 cell lines. In conclusion, the functional IL13 polymorphism, rs1800925T, previously associated with risk of schistosomiasis, also contributes to risk of late-stage schistosomiasis caused by S. japonicum. PMID- 26258682 TI - Cell type-specific manipulation with GFP-dependent Cre recombinase. AB - There are many transgenic GFP reporter lines that allow the visualization of specific populations of cells. Using such lines for functional studies requires a method that transforms GFP into a molecule that enables genetic manipulation. We developed a method that exploits GFP for gene manipulation, Cre recombinase dependent on GFP (CRE-DOG), a split component system that uses GFP and its derivatives to directly induce Cre/loxP recombination. Using plasmid electroporation and AAV viral vectors, we delivered CRE-DOG to multiple GFP mouse lines, which led to effective recombination selectively in GFP-labeled cells. Furthermore, CRE-DOG enabled optogenetic control of these neurons. Beyond providing a new set of tools for manipulation of gene expression selectively in GFP(+) cells, we found that GFP can be used to reconstitute the activity of a protein not known to have a modular structure, suggesting that this strategy might be applicable to a wide range of proteins. PMID- 26258683 TI - EAG2 potassium channel with evolutionarily conserved function as a brain tumor target. AB - Over 20% of the drugs for treating human diseases target ion channels, but no cancer drug approved by the US Food and Drug Administration (FDA) is intended to target an ion channel. We found that the EAG2 (Ether-a-go-go 2) potassium channel has an evolutionarily conserved function for promoting brain tumor growth and metastasis, delineate downstream pathways, and uncover a mechanism for different potassium channels to functionally cooperate and regulate mitotic cell volume and tumor progression. EAG2 potassium channel was enriched at the trailing edge of migrating medulloblastoma (MB) cells to regulate local cell volume dynamics, thereby facilitating cell motility. We identified the FDA-approved antipsychotic drug thioridazine as an EAG2 channel blocker that reduces xenografted MB growth and metastasis, and present a case report of repurposing thioridazine for treating a human patient. Our findings illustrate the potential of targeting ion channels in cancer treatment. PMID- 26258684 TI - Parity and longevity of Aedes aegypti according to temperatures in controlled conditions and consequences on dengue transmission risks. AB - BACKGROUND: In Guadeloupe, Aedes aegypti mosquitoes are the only vectors of dengue and chikungunya viruses. For both diseases, vector control is the only tool for preventing epidemics since no vaccine or specific treatment is available. However, to efficiently implement control of mosquitoes vectors, a reliable estimation of the transmission risks is necessary. To become infective an Ae. aegypti female must ingest the virus during a blood meal and will not be able to transmit the virus during another blood-meal until the extrinsic incubation period is completed. Consequently the aged females will carry more infectious risks. The objectives of the present study were to estimate under controlled conditions the expectation of infective life for females and thus the transmission risks in relation with their reproductive cycle and parity status. METHODOLOGY/PRINCIPAL FINDINGS: Larvae of Ae. aegypti were collected in central Guadeloupe and breed under laboratory conditions until adult emergence. The experiments were performed at constant temperatures (+/- 1.5 degrees C) of 24 degrees C, 27 degrees C and 30 degrees C on adults females from first generation (F1). Females were kept and fed individually and records of blood-feeding, egg laying and survival were done daily. Some females were dissected at different physiological stages to observe the ovaries development. The data were analyzed to follow the evolution of parity rates, the number of gonotrophic cycles, the fecundity and to study the mean expectation of life and the mean expectation of infective life for Ae. aegypti females according to temperatures. The expectation of life varies with the parity rates and according to the temperatures, with durations from about 10 days at low parity rates at the higher temperature to an optimal duration of about 35 days when 70% of females are parous at 27 degrees C. Infective life expectancy was found highly variable in the lower parous rates and again the optimal durations were found when more than 50% of females are parous for the mean temperatures of 27 degrees C and 30 degrees C. CONCLUSION: Parity rates can be determined for field collected females and could be a good proxy of the expectation of infective life according to temperatures. However, for the same parity rates, the estimation of infective life expectation is very different between Ae. aegypti and Anopheles gambiae mosquitoes. Correlation of field parity rates with transmission risks requires absolutely to be based on Ae. aegypti models, since available Anopheles sp. models underestimate greatly the females longevity. PMID- 26258685 TI - In Vitro Enzymatic Activities of Bacteriochlorophyll a Synthase Derived from the Green Sulfur Photosynthetic Bacterium Chlorobaculum tepidum. AB - The activity of an enzyme encoded by the CT1610 gene in the green sulfur photosynthetic bacterium Chlorobaculum tepidum, which was annotated as bacteriochlorophyll (BChl) a synthase, BchG (denoted as tepBchG), was examined in vitro using the lysates of Escherichia coli containing the heterologously expressed enzyme. BChl a possessing a geranylgeranyl group at the 17-propionate residue (BChl aGG) was produced from bacteriochlorophyllide (BChlide) a and geranylgeranyl pyrophosphate in the presence of tepBchG. Surprisingly, tepBchG catalyzed the formation of BChl a bearing a farnesyl group (BChl aF) as in the enzymatic production of BChl aGG, indicating loose recognition of isoprenoid pyrophosphates in tepBchG. In contrast to such loose recognition of isoprenoid substrates, BChlide c and chlorophyllide a gave no esterifying product upon being incubated with geranylgeranyl or farnesyl pyrophosphate in the presence of tepBchG. These results confirm that tepBchG undoubtedly acts as the BChl a synthase in Cba. tepidum. The enzymatic activity of tepBchG was higher than that of BchG of Rhodobacter sphaeroides at 45 degrees C, although the former activity was lower than the latter below 35 degrees C. PMID- 26258687 TI - Oestrogens as apoptosis regulators in mammalian testis: angels or devils? AB - In the mammalian testis, spermatogenesis is a highly coordinated process of germ cell development, which ends with the release of 'mature' spermatozoa. The fine regulation of spermatogenesis is strictly dependent on sex steroid hormones, which orchestrate the cellular and molecular events underlying normal development of germ cells. Sex steroids actions also rely on the control of germ cell survival, and the programmed cell death by apoptosis has been indicated as a critical process in regulating the size and quality of the germ line. Recently, oestrogens have emerged as important regulators of germ cell fate. However, the beneficial or detrimental effects of oestrogens in spermatogenesis are controversial, with independent reports arguing for their role as cell survival factors or as apoptosis-inducers. The dual behaviour of oestrogens, shifting from 'angels to devils' is supported by the clinical findings of increased oestrogens levels in serum and intratesticular milieu of idiopathic infertile men. This review aims to discuss the available information concerning the role of oestrogens in the control of germ cell death and summarises the signalling mechanisms driven oestrogen-induced apoptosis. The present data represent a valuable basis for the clinical management of hyperoestrogenism-related infertility and provide a rationale for the use of oestrogen-target therapies in male infertility. PMID- 26258689 TI - Blood-Compatible Polymer for Hepatocyte Culture with High Hepatocyte-Specific Functions toward Bioartificial Liver Development. AB - The development of bioartificial liver (BAL) is expected because of the shortage of donor liver for transplantation. The substrates for BAL require the following criteria: (a) blood compatibility, (b) hepatocyte adhesiveness, and (c) the ability to maintain hepatocyte-specific functions. Here, we examined blood compatible poly(2-methoxyethyl acrylate) (PMEA) and poly(tetrahydrofurfuryl acrylate) (PTHFA) (PTHFA) as the substrates for BAL. HepG2, a human hepatocyte model, could adhere on PMEA and PTHFA substrates. The spreading of HepG2 cells was suppressed on PMEA substrates because integrin contribution to cell adhesion on PMEA substrate was low and integrin signaling was not sufficiently activated. Hepatocyte-specific gene expression in HepG2 cells increased on PMEA substrate, whereas the expression decreased on PTHFA substrates due to the nuclear localization of Yes-associated protein (YAP). These results indicate that blood compatible PMEA is suitable for BAL substrate. Also, PMEA is expected to be used to regulate cell functions for blood-contacting tissue engineering. PMID- 26258686 TI - Correlation of lung collapse and gas exchange - a computer tomographic study in sheep and pigs with atelectasis in otherwise normal lungs. AB - BACKGROUND: Atelectasis can provoke pulmonary and non-pulmonary complications after general anaesthesia. Unfortunately, there is no instrument to estimate atelectasis and prompt changes of mechanical ventilation during general anaesthesia. Although arterial partial pressure of oxygen (PaO2) and intrapulmonary shunt have both been suggested to correlate with atelectasis, studies yielded inconsistent results. Therefore, we investigated these correlations. METHODS: Shunt, PaO2 and atelectasis were measured in 11 sheep and 23 pigs with otherwise normal lungs. In pigs, contrasting measurements were available 12 hours after induction of acute respiratory distress syndrome (ARDS). Atelectasis was calculated by computed tomography relative to total lung mass (Mtotal). We logarithmically transformed PaO2 (lnPaO2) to linearize its relationships with shunt and atelectasis. Data are given as median (interquartile range). RESULTS: Mtotal was 768 (715-884) g in sheep and 543 (503-583) g in pigs. Atelectasis was 26 (16-47) % in sheep and 18 (13-23) % in pigs. PaO2 (FiO2 = 1.0) was 242 (106-414) mmHg in sheep and 480 (437-514) mmHg in pigs. Shunt was 39 (29 51) % in sheep and 15 (11-20) % in pigs. Atelectasis correlated closely with lnPaO2 (R2 = 0.78) and shunt (R2 = 0.79) in sheep (P-values<0.0001). The correlation of atelectasis with lnPaO2 (R2 = 0.63) and shunt (R2 = 0.34) was weaker in pigs, but R2 increased to 0.71 for lnPaO2 and 0.72 for shunt 12 hours after induction of ARDS. In both, sheep and pigs, changes in atelectasis correlated strongly with corresponding changes in lnPaO2 and shunt. DISCUSSION AND CONCLUSION: In lung-healthy sheep, atelectasis correlates closely with lnPaO2 and shunt, when blood gases are measured during ventilation with pure oxygen. In lung-healthy pigs, these correlations were significantly weaker, likely because pigs have stronger hypoxic pulmonary vasoconstriction (HPV) than sheep and humans. Nevertheless, correlations improved also in pigs after blunting of HPV during ARDS. In humans, the observed relationships may aid in assessing anaesthesia-related atelectasis. PMID- 26258690 TI - Discovery of a Novel Class of Negative Allosteric Modulator of the Dopamine D2 Receptor Through Fragmentation of a Bitopic Ligand. AB - Recently, we have demonstrated that N-((trans)-4-(2-(7-cyano-3,4 dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide (SB269652) (1) adopts a bitopic pose at one protomer of a dopamine D2 receptor (D2R) dimer to negatively modulate the binding of dopamine at the other protomer. The 1H indole-2-carboxamide moiety of 1 extends into a secondary pocket between the extracellular ends of TM2 and TM7 within the D2R protomer. To target this putative allosteric site, we generated and characterized fragments that include and extend from the 1H-indole-2-carboxamide moiety of 1. N-Isopropyl-1H-indole-2 carboxamide (3) displayed allosteric pharmacology and sensitivity to mutations of the same residues at the top of TM2 as was observed for 1. Using 3 as an "allosteric lead", we designed and synthesized an extensive fragment library to generate novel SAR and identify N-butyl-1H-indole-2-carboxamide (11d), which displayed both increased negative cooperativity and affinity for the D2R. These data illustrate that fragmentation of extended compounds can expose fragments with purely allosteric pharmacology. PMID- 26258691 TI - Adult Behcet's disease in Iran: analysis of 6075 patients. AB - INTRODUCTION: This is an analysis of adult Behcet's disease (BD) in Iran, from the Iran Registry of 7187 BD patients, gathered from 1975 to 2014, among which 6075 were adults (84.5%). PATIENTS: Patients were seen by a multidisciplinary team of experts. The diagnosis was by expert opinion, not by any specific classification/diagnosis criteria. However, 96.8% of them were classified by the International Criteria for Behcet's Disease (ICBD). Adult BDs were patients who had their first manifestation at the age of 16 or later. RESULTS: Males constituted 56% (male/female ratio 1.3/1). The mean age at onset was 28.3 +/- 8.7, mean duration 10.8 +/- 8.2, and mean follow-up 5.0 +/- 6.3. Oral aphthosis was seen in 97.5%, genital aphthosis 65.7%, skin manifestations 64.6% (pseudofolliculitis 53.2%, erythema nodosum 23.9%), ocular manifestations 58.1% (anterior uveitis 41.1%, posterior uveitis 45%, retinal vasculitis 33.6%, cataract 24.4%), joint manifestations 39.4% (arthralgia 18.9%, monoarthritis 9.1%, oligoarthritis 17.8%, ankyloing spondylitis 2%), gastrointestinal manifestations 7% (gastroduodenitis 2.3%, peptic ulcer 1.2%, diarrhea 2.1%, rectorrhagia 1.0%, abdominal pain-nausea 1.8%), neurological manifestations 10.6% (central 3.7%, peripheral 0.3%, headache 7.6%), vessel involvement (large vessel 1.7% with large vein thrombosis 1.1% and arterial involvement 0.7%, phlebitis 6.6%, superficial phlebitis 2.3%), epididymitis 4.6%, pulmonary manifestations 1% and cardiac manifestations 0.6%. Positive pathergy test was seen in 52.3%, human leukocyte antigen (HLA)-B5 in 54%, HLA-B51 in 48.9%, and high erythrocyte sedimentation rate in 52.8% of patients. By International Study Group (ISG) criteria 77.9% were classified, compared to ICBD revised criteria with 96.9%. The specificity of ISG was 99.2% and ICBD 97.2%. CONCLUSION: Results are near the nationwide surveys from Japan, China, Korea and Germany. PMID- 26258693 TI - Importance of chemistry, nutrition and technology in rice processing. PMID- 26258692 TI - Cerebrospinal Fluid Patterns and the Risk of Future Dementia in Early, Incident Parkinson Disease. AB - IMPORTANCE: Alterations in cerebrospinal fluid (CSF) have been found in Parkinson disease (PD) and in PD dementia (PDD), but the prognostic importance of such changes is not well known. In vivo biomarkers for disease processes in PD are important for future development of disease-modifying therapies. OBJECTIVE: To assess the diagnostic and prognostic value of a panel of CSF biomarkers in patients with early PD and related disorders. DESIGN, SETTING, AND PARTICIPANTS: Regional population-based, prospective cohort study of idiopathic parkinsonism that included patients diagnosed between January 1, 2004, and April 30, 2009, by a movement disorder team at a university hospital that represented the only neurology clinic in the region. Participants were 128 nondemented patients with new-onset parkinsonism (104 with PD, 11 with multiple system atrophy, and 13 with progressive supranuclear palsy) who were followed up for 5 to 9 years. At baseline, CSF from 30 healthy control participants was obtained for comparison. MAIN OUTCOMES AND MEASURES: Cerebrospinal fluid concentrations of neurofilament light chain protein, Abeta1-42, total tau, phosphorylated tau, alpha-synuclein, and heart fatty acid-binding protein were quantified by 2 blinded measurements (at baseline and after 1 year). Follow-up included an extensive neuropsychological assessment. As PD outcome variables, mild cognitive impairment and incident PDD were diagnosed based on published criteria. RESULTS: Among the 128 study participants, the 104 patients with early PD had a different CSF pattern compared with the 13 patients with progressive supranuclear palsy (baseline area under the receiver operating characteristic curve, 0.87; P < .0001) and the 30 control participants (baseline area under the receiver operating characteristic curve, 0.69; P = .0021). A CSF biomarker pattern associated with the development of PDD was observed. In PD, high neurofilament light chain protein, low Abeta1-42, and high heart fatty acid-binding protein at baseline were related to future PDD as analyzed by Cox proportional hazards regression models. Combined, these early biomarkers predicted PDD with high accuracy (hazard ratio, 11.8; 95% CI, 3.3-42.1; P = .0001) after adjusting for possible confounders. CONCLUSIONS AND RELEVANCE: The analyzed CSF biomarkers have potential usefulness as a diagnostic tool in patients with parkinsonism. In PD, high neurofilament light chain protein, low Abeta1-42, and high heart fatty acid binding protein were related to future PDD, providing new insights into the etiology of PDD. PMID- 26258694 TI - Determination of some minerals and beta-carotene contents in aromatic indica rice (Oryza sativa L.) germplasm. AB - 39 aromatic indica rice (Oryza sativa L.) cultivars were characterized for Iron, Zinc, Calcium, Magnesium, Copper and beta-carotene contents. The beta-carotene contents were ranging from 1.23 to 9.9MUg/g in brown and 0.08 to 1.99MUg/g in milled rice. Among the mineral contents, Magnesium was found ranging from 855MUg/g (Gham) to maximum of 1636MUg/g (Badshahbhog) followed by Iron in 32MUg/g (Jirga) to 218MUg/g (Kalsal), Copper content from 2MUg/g (Girga) to 1004MUg/g (Gham), Zinc content from 25 (Gham) to 165MUg/g (Ambemohar-157) and Calcium ranged from 14MUg/g (Ambemohar pandhara) to 67MUg/g (Kate chinoor). The study showed that the germplasm assessed is a good source of micronutrients and can be further exploited in breeding programme. PMID- 26258695 TI - Simple and rapid determination of free fatty acids in brown rice by FTIR spectroscopy in conjunction with a second-derivative treatment. AB - A simple and rapid method for the determination of free fatty acid (FFA) content in brown rice using Fourier transform infrared spectroscopy (FTIR) in conjunction with second-derivative treatment was proposed. Ground brown rice (10g) was soaked in toluene (20mL) for 30min, and the filtrate of the extract was placed in a 1mm CaF2 liquid cell. The transmittance spectrum of the filtrate was recorded using toluene for the background spectrum. The absorption band due to the CO stretching mode of FFAs was detected at 1710cm(-1), and the Savitzky-Golay second-derivative treatment was performed for band separation. A single linear regression model for FFA was developed using the 1710cm(-1) band in the second-derivative spectra of oleic acid in toluene (0.25-2.50gL(-1)), and the model displayed high prediction accuracy with a determination coefficient of 0.998 and a root mean square error of 0.03gL(-1). PMID- 26258696 TI - Extraction of anthocyanins and polyphenols from black rice (Oryza sativa L.) by modeling and assessing their reversibility and stability. AB - This study was aimed the extraction of total flavonoids, anthocyanins and phenolics, as well as the antioxidant activity of black rice (Oryza sativa) and to study the stability in relation to pH, light and copigmentation. Variations in temperature (10-50 degrees C), time (20-80min), and solid-solvent ratio (1:15 1:45) were studied using a Box-Behnken design. The regression models were significant (P<0.001) and determination coefficients ?0.900. Extraction at 34.7 degrees C for 80min using a solid:solvent ratio of 1:30 rendered an extract with 51.26mg 100g(-1) of flavonoids, 116.58mg 100g(-1) of anthocyanins, 520.17mg 100g( 1) of phenolics and 46.50% inhibition of the DPPH radical. A decrease in the color intensity was observed when pH values were changed while anthocyanins were reversible in the process of protonation/deprotonation. The addition of glucose, phytic and gallic acids in the optimized extract exposed to light displayed an intermolecular copigmentation. The main anthocyanin identified in black rice was cyanidin-3-glucoside. PMID- 26258698 TI - Effects of aleurone layer on rice cooking: A histological investigation. AB - Understanding how aleurone layer (AL) affects rice cooking behaviour is important for rice processing. Individual effects of AL on rice cooking behaviour were evaluated and histological characters of AL before and after cooking were investigated. AL slightly affected rice cooking quality (optimum cooking time, water absorption, volume expansion ratio and total solids loss) while remarkably affected rice texture (hardness and adhesiveness) and peak viscosity. Histological investigation showed that channels were formed in AL during cooking. The channels facilitated the penetration of water, which could explain why AL exhibited slight effects on rice cooking quality. In addition, thick cell walls and thermally stable aleurone grains were widely distributed in AL. Leached components accumulated on them and formed a reinforced coated film on rice surface during cooking, which may be a possible mechanism accounting for the remarkable effect of AL on rice texture. Histological characters of AL are closely related with rice cooking behaviour. PMID- 26258697 TI - Development of NIRS models to predict protein and amylose content of brown rice and proximate compositions of rice bran. AB - With the escalating persuasion of economic and nutritional importance of rice grain protein and nutritional components of rice bran (RB), NIRS can be an effective tool for high throughput screening in rice breeding programme. Optimization of NIRS is prerequisite for accurate prediction of grain quality parameters. In the present study, 173 brown rice (BR) and 86 RB samples with a wide range of values were used to compare the calibration models generated by different chemometrics for grain protein (GPC) and amylose content (AC) of BR and proximate compositions (protein, crude oil, moisture, ash and fiber content) of RB. Various modified partial least square (mPLSs) models corresponding with the best mathematical treatments were identified for all components. Another set of 29 genotypes derived from the breeding programme were employed for the external validation of these calibration models. High accuracy of all these calibration and prediction models was ensured through pair t-test and correlation regression analysis between reference and predicted values. PMID- 26258699 TI - Characterization of rice starch and protein obtained by a fast alkaline extraction method. AB - This study evaluated the characteristics of rice starch and protein obtained by a fast alkaline extraction method on rice flour (RF) derived from broken rice. The extraction was conducted using 0.18% NaOH at 30 degrees C for 30min followed by centrifugation to separate the starch rich and the protein rich fractions. This fast extraction method allowed to obtain an isoelectric precipitation protein concentrate (IPPC) with 79% protein and a starchy product with low protein content. The amino acid content of IPPC was practically unchanged compared to the protein in RF. The proteins of the IPPC underwent denaturation during extraction and some of the starch suffered the cold gelatinization phenomenon, due to the alkaline treatment. With some modifications, the fast method can be interesting in a technological point of view as it enables process cost reduction and useful ingredients obtention to the food and chemical industries. PMID- 26258700 TI - Relationships of damaged starch granules and particle size distribution with pasting and thermal profiles of milled MR263 rice flour. AB - This research was conducted to investigate the effects of different grinding techniques (dry, semi-wet and wet) of milled rice grains on the damaged starch and particle size distribution of flour produced from a new variety, MR263, specifically related to the pasting and thermal profiles. The results indicated that grinding techniques significantly (p<0.05) affected starch damage content and particle size distribution of rice flour. Wet grinding process yields flour with lowest percentage of starch damage (7.37%) and finest average particle size (8.52MUm). Pasting and gelatinization temperature was found in the range of 84.45 89.63 degrees C and 59.86-75.31 degrees C, respectively. Dry ground flour attained the lowest pasting and gelatinization temperature as shown by the thermal and pasting profiles. Correlation analysis revealed that percentage of damaged starch granules had a significant, negative relationship with pasting temperature while average particle size distribution had a significant, strong negative relationship with gelatinization temperature. PMID- 26258701 TI - Effect of succinylation on functional and morphological properties of starches from broken kernels of Pakistani Basmati and Irri rice cultivars. AB - Starch extracted from broken kernels of Basmati and Irri rice varieties of Pakistani rice were subjected to modification by addition of succinic anhydride at levels of 2%, 4% and 5% based on dried weight of starch. The succinyl content of Irri rice starch increased with the concentration of succinic anhydride. Scanning electron micrographs revealed presence of dents and fusion of rice starch granules. Swelling power and water retention capacity (WRC) significantly improved after succinylation while on refrigerated storage percent decline in paste clarity of modified rice starches was stable as compared to native Basmati (BC) and Irri (IC) rice starches. Succinylation also reduced solubility, pasting temperature (PT) and gel hardness of starch gels. Improvement was observed in cold storage stability of rice starch succinates as evident from textural profile analysis. PMID- 26258702 TI - Physicochemical and structural characteristics of rice starch modified by irradiation. AB - This work evaluated the physicochemical and structural properties of rice starch of the cultivars IAC 202 and IRGA 417 modified by irradiation. Starch samples were irradiated by (60)Co in doses 1, 2 and 5kGy, on a rate of 0.4kGy/h. A control not irradiated was used for comparison. The granule morphology and A-type X-ray diffraction pattern were not altered by irradiation. There was an increase in amylose content, carboxyl content and acidity with irradiation. Gamma radiation did not affect the thermal properties of IAC202, but increased gelatinization temperature of IRGA417, in the higher dose (5kGy). The number of long chains of amylopectin was reduced and short chains were increased for IAC202, whereas for IRGA 417, the opposite was observed, probably due to cross linking of starch chains. Starches had their physicochemical and structural properties modified by irradiation differently. PMID- 26258703 TI - Resistant starch improvement of rice starches under a combination of acid and heat-moisture treatments. AB - The effects of a combination of acid and heat-moisture treatment on formation of resistant starch (RS) and characteristics of high-amylose, normal and waxy rice starches were investigated in this study. The degrees of polymerization of the rice starches treated with citric acid, lactic acid or acetic acid were significantly reduced as compared to the native starches. The RS contents of acid and heat-moisture treated rice starches were in a range of 30.1-39.0%, significantly higher than those of native rice starches (6.3-10.2%) and those of heat-moisture treated rice starches (18.5-23.9%). The acid and heat-moisture treatments reduced swelling power and viscosity, but increased solubility of the starches, while the crystalline structure did not change. Among the organic acids used, citric acid had the most impact on starch characteristics and RS formation, followed by lactic acid and acetic acid. The results are useful in production of RS for functional food application. PMID- 26258704 TI - In vitro digestibility and in vivo glucose response of native and physically modified rice starches varying amylose contents. AB - The native and physically modified rice starches with varying amylose contents were subjected to investigate the in vitro digestibility and the in vivo glucose tolerance in mice. The amylose and resistant starch (RS) contents of five native rice starches ranged in 4.7-30.6% and 6.3-11.8%, respectively. The RS contents of rice starches increased to 18.5-23.9% after heat-moisture treatment (HMT) and to 19.5-26.9% after annealing treatment (ANN). The heat-moisture and annealing treatments significantly reduced glycemic index (GI) values of the rice starches. GI values of the native, heat-moisture treated and annealed rice starches ranged in 68.9-100, 61.2-88.9 and 21.2-43.9, respectively. There was no correlation between amylose contents and the RS contents or GI values, while a strong negative correlation between RS contents and GI values was found (R(2)=-0.747, P<0.01). PMID- 26258705 TI - From rice bag to table: Fate of phenolic chemical compositions and antioxidant activities in waxy and non-waxy black rice during home cooking. AB - The objectives of this study were to systematically analyze degradation rate of functional substances, such as total phenolic content (TPC), total flavonoid content (TFC), condensed tannin content (CTC), monomeric anthocyanin content (MAC), cyanidin-3-glucoside (Cy3glc), and peonidin-3-glucoside (Pn3glc), as well as antioxidant activities in cooked waxy and non-waxy black rice through different home cooking manners. Results showed that greater phenolics and antioxidant capacities were detected in non-waxy rice rather than waxy one. All processed black rice exhibited significantly (p<0.05) lower TPC, TFC, CTC, MAC, Cy3glc, Pn3glc, and antioxidants as compared to the raw rice. Different processing methods significantly degraded the content and activities of antioxidants of both waxy and non-waxy black rice. Under the same cooking time, black rice porridge retained more active substances than that of cooked rice by rice cooker. Therefore, to maintain bioavailability of active components, black rice porridge may gain more health promoting effects. PMID- 26258706 TI - Impact of structural characteristics on starch digestibility of cooked rice. AB - To examine the impact of structural characteristics of cooked rice grains on their starch digestibility, a simulated in vitro gastro-small intestinal digestion technique was applied to intact and homogenised cooked rice samples. The starch hydrolysis percentage increased during simulated small intestinal digestion, in which approximately 65% and 24% of the starch was hydrolysed within the first 5min, for homogenised and intact cooked rice, respectively. The kinetic constant of homogenised cooked rice, which was regarded as an estimated digestion rate, was ~8 times higher than the intact cooked rice. The homogenised and intact samples were also examined for any microstructural changes occurring during the in vitro digestion process using fluorescent and scanning electron microscopy. In the intact samples, the aleurone layers of the endosperm remained as thin-film like layers during in vitro digestion and thus may be regarded as less digestible materials that influence cooked rice digestibility. PMID- 26258707 TI - Impact of the degree of cooking on starch digestibility of rice - An in vitro study. AB - The impact of cooking degree on the starch digestibility of a non-waxy, cooked rice was examined through a simulated gastro-small intestinal in vitro digestion model. The starch hydrolysis of both non-homogenised and homogenised cooked rice samples during simulated digestion was also compared in order to examine the impact of grain structure on starch digestibility. Polished rice grains were cooked in boiling water for 10min (partially cooked) and 20min (fully cooked) to obtain samples of different cooking degree. No significant differences in the equilibrium starch hydrolysis (%) were observed among the partially and fully cooked grains, although significant differences were observed among the uncooked and cooked samples. The equilibrium starch hydrolysis (%) of homogenised rice was higher than its non-homogenised counterpart. These results showed that rice starch digestibility should not be affected by the cooking degrees related to starch gelatinisation, but was influenced by the modification/destruction of the grain structure during mechanical processing. PMID- 26258708 TI - Polishing and parboiling effect on the nutritional and technological properties of pigmented rice. AB - This study aims to evaluate the effects of polishing and parboiling on proximate composition, structure, phenolic compounds, antioxidant activity, cooking time and hardness of IAC-600 black rice cultivar and MPB-10 red rice lineage. Proximate analysis and light micrographs revealed higher migration of red rice proteins than black rice proteins to the endosperm as a result of parboiling. Parboiling reduced the ash content of red rice while no difference was determined in black rice. Gelatinized starch granules from both genotypes showed similar appearance. There was a decrease in relative crystallinity on both black and red rice subjected to parboiling, which was an indicative of crystallites disruption. Polishing removed more than 90% of free phenolics for both genotypes, while parboiling allowed the partial preservation of free phenolics content in polished rice. Parboiling induced an increase in the cooking time of red rice, but a decrease in the cooking time of black rice. PMID- 26258709 TI - Conventional steaming retains tocols and gamma-oryzanol better than boiling and frying in the jasmine rice variety Khao dok mali 105. AB - The aim of this study was to determine the effect of various cooking methods on the white rice (WR), brown rice (BR) and parboiled geminated brown rice (PGBR) of the same variety, focusing on gamma-oryzanol and tocols. The methods used for analysis of gamma-oryzanol and tocols included solvent extraction and HPLC. The results indicated that PGBR had a higher content of gamma-oryzanol and tocols compared to BR and WR, when different cooking methods (raw, steamed, boiled and fried) were used. Steaming method retained the higher gamma-oryzanol content (53.6-62.2mg/100g) in both PGBR and BR, in comparison with boiling (53.0 60.6mg/100g) and frying (23.4-31.5mg/100g) methods. Frying reduced the gamma oryzanol content significantly regardless of the rice type. Regarding tocols, a similar trend was noticed in all the methods studied. Tocotrienol was the most abundant tocol found in PGBR and BR. Therefore, steaming is the best cooking method to preserved most of the bioactive compounds; however, a slight increase in total tocols was observed after frying. PMID- 26258710 TI - An improved process for high nutrition of germinated brown rice production: Low pressure plasma. AB - Brown rice was exposed to low-pressure plasma ranging from 1 to 3kV for 10min. Treatment of brown rice in low-pressure plasma increases the germination percentage, seedling length, and water uptake in laboratory germination tests. Of the various treatments, 3-kV plasma exposure for 10min yielded the best results. In germinating brown rice, alpha-amylase activity was significantly higher in treated groups than in controls. The higher enzyme activity in plasma-treated brown rice likely triggers the rapid germination and earlier vigor of the seedlings. Low-pressure plasma also increased gamma-aminobutyric acid (GABA) levels from ~19 to ~28mg/100g. In addition, a marked increase in the antioxidant activity of brown rice was observed with plasma treatments compared to controls. The main finding of this study indicates that low-pressure plasma is effective at enhancing the growth and GABA accumulation of germinated brown rice, which can supply high nutrition to consumer. PMID- 26258711 TI - Inorganic arsenic in rice-based products for infants and young children. AB - Inorganic arsenic (Asi) is a chronic, non-threshold carcinogen. Rice and rice based products can be the major source of Asi for many subpopulations. Baby rice, rice cereals and rice crackers are widely used to feed infants and young children. The Asi concentration in rice-based products may pose a health risk for infants and young children. Asi concentration was determined in rice-based products produced in the European Union and risk assessment associated with the consumption of these products by infants and young children, and compared to an identical US FDA survey. There are currently no European Union or United States of America regulations applicable to Asi in food. However, this study suggests that the samples evaluated may introduce significant concentration of Asi into infants' and young children's diets. Thus, there is an urgent need for regulatory limits on Asi in food, especially for baby rice-based products. PMID- 26258712 TI - Towards rice bran protein utilization: In silico insight on the role of oryzacystatins in biologically-active peptide production. AB - Rice bran proteins (RBP) have been demonstrated to harbour biologically active peptides, which can be released by proteases and applied in human health promotion. In this study, the roles of rice bran cysteine protease inhibitors, oryzacystatins, were considered for efficient production of bioactive peptides from RBP. In silico evidence demonstrates that aspartate protease (pepsin at pH>2) and metalloproteinase (thermolysin) have strong prospects for use in simultaneously cleaving the QXVXGX motif of oryzacystatins, which can lead to their inactivation, and in releasing bioactive sequences from the protease inhibitors. The cleaved bioactive peptides are known to possess activities that can be applied in the management of hypertension, oxidative stress, type 2 diabetes mellitus and other aberrant cellular processes. Moreover, several potentially bioactive di- and tripeptides were identified in oryzacystatin peptide pools. This study provides an important consideration and a direction that can lead to efficient release of bioactive peptides from rice bran proteins for functional food applications. PMID- 26258713 TI - Effect of puffing on physical and antioxidant properties of brown rice. AB - The objective of this study was to investigate the effect of puffing process on the physical, antioxidant properties and mineral composition of brown rice. Bulk density significantly varied (P<0.05) among the puffing stages and was lowest in expanded rice. From Hunter colour analysis, the lowest L(*) value and highest a(*) and b(*) values were observed for parboiled rice (P<0.05). A-type of diffraction pattern, observed in raw rice was altered by puffing process and led to the formation of B- and V-type patterns. Raman spectrum showed the intense peaks in raw rice and the intensity of those peaks was decreased during the puffing process. Scanning electron microscopy revealed a highly porous structure of expanded rice kernel. Significant decrease in the antioxidant properties was observed upon puffing process as compared to raw rice samples. Hence the present study demonstrates that the puffing process leads to the significant changes in the properties of brown rice. PMID- 26258714 TI - Utilization of sorghum, rice, corn flours with potato starch for the preparation of gluten-free pasta. AB - The aim of this study was to evaluate the use of mixture of sorghum-rice-corn flour and potato starch in the development of gluten-free pasta for celiac disease patients. The experiment was designed according to simplex-lattice method and different types of gluten-free flours were used, such as sorghum, rice, corn, and potato starch. The fifteen formulations were subjected to sensory analysis (Mixed Structured Scale - MSS) and seven formulations were selected in respect to taste and grittiness. These formulations were subjected to Quantitative Descriptive Analysis (QDA), which evaluated the attributes: appearance, color, odor, hardness, elasticity, stickiness, grittiness, taste, residual bitterness and overall quality. Results showed significant difference in appearance, color and hardness. The formulations that showed the best sensory results were submitted to chemical analysis and cooking quality of pasta. It was observed that the best results for mixing is sorghum flour, rice flour and potato starch. PMID- 26258715 TI - Physical, physicochemical and nutritional characteristics of Bhoja chaul, a traditional ready-to-eat dry heat parboiled rice product processed by an improvised soaking technique. AB - Bhoja chaul is a traditional whole rice product processed by the dry heat parboiling technique of low amylose/waxy paddy that is eaten after soaking in water and requires no cooking. The essential steps in Bhoja chaul making are soaking paddy in water, roasting with sand, drying and milling. In this study, the product was prepared from a low amylose variety and a waxy rice variety by an improvised laboratory scale technique. Bhoja chaul prepared in the laboratory by this technique was studied for physical, physicochemical, and textural properties. Improvised method shortened the processing time and gave a product with good textural characteristics. Shape of the rice kernels became bolder on processing. RVA studies and DSC endotherms suggested molecular damage and amylose lipid complex formation by the linear B-chains of amylopectin, respectively. X ray diffractography indicated formation of partial B-type pattern. Shifting of the crystalline region of the XRD curve towards lower values of Bragg's angle was attributed to the overall increase in inter-planar spacing of the crystalline lamellae. Resistant starch was negligible. Bhoja chaul may be useful for children and people with poor state of digestibility. PMID- 26258716 TI - Increased Peripheral Blood Pro-Inflammatory/Cytotoxic Lymphocytes in Children with Bronchiectasis. AB - OBJECTIVE: Bronchiectasis (BE) in children is common in some communities including Indigenous children in Australia. Relatively little is known about the nature of systemic inflammation in these children, especially the contribution of specific pro-inflammatory and cytotoxic lymphocyte subsets: T-cells, natural killer (NK) cells and NKT-like cells. We have shown that these cells produce increased cytotoxic (granzyme b and perforin) and inflammatory (IFNgamma and TNFalpha) mediators in several adult chronic lung diseases and hypothesised that similar changes would be evident in children with BE. METHODS: Intracellular cytotoxic mediators perforin and granzyme b and pro-inflammatory cytokines were measured in T cell subsets, NKT-like and NK cells from blood and bronchoalveolar samples from 12 children with BE and 10 aged-matched control children using flow cytometry. RESULTS: There was a significant increase in the percentage of CD8+ T cells and T and NKT-like subsets expressing perforin/granzyme and IFNgamma and TNFalpha in blood in BE compared with controls. There was a further increase in the percentage of pro-inflammatory cytotoxic T cells in Indigenous compared with non-Indigenous children. There was no change in any of these mediators in BAL. CONCLUSIONS: Childhood bronchiectasis is associated with increased systemic pro inflammatory/cytotoxic lymphocytes in the peripheral blood. Future studies need to examine the extent to which elevated levels of pro-inflammatory cytotoxic cells predict future co-morbidities. PMID- 26258717 TI - Early results of MitraClip system implantation by real-time three-dimensional speckle-tracking left ventricle analysis. AB - AIMS: To appraise the early effect of percutaneous mitral valve repair with the MitraClip system on myocardial function using real-time three-dimensional speckle tracking echocardiography (3D-STE). METHODS: Consecutive patients with moderate to-severe or severe mitral regurgitation, undergoing mitral valve repair with the MitraClip system, were prospectively evaluated during the peri-procedural workout and follow-up. Left ventricular deformation was evaluated by a two-dimensional and 3D speckle-tracking analysis. 3D-STE acquisitions were elaborated obtaining real-time 3D global longitudinal strain evaluation, and by appraising both volumetric and hemodynamic parameters (i.e. left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular ejection fraction, cardiac output, and stroke volume). RESULTS: In all, 30 patients were included. At 1-month follow-up, 3D-STE analysis revealed no changes in left ventricular end diastolic volume (162.6 +/- 73.7 ml at baseline vs. 159.8 +/- 64.5 ml at 1-month follow-up; P = 0.63) and a downward trend in left ventricular end-systolic volume (104.7 +/- 52.0 vs. 100.1 +/- 50.4 ml, respectively; P = 0.06). Left ventricular ejection fraction did not significantly increase (38.1 +/- 11.3% at baseline vs. 39.4 +/- 11.0% at 1-month follow-up; P = 0.20). No significant changes were reported in cardiac output (4.3 +/- 2.0 l/min at baseline vs. 4.0 +/- 1.5 l/min at follow-up; P = 0.377) and in stroke volume (59.5 +/- 25.5 ml at baseline vs. 59.9 +/- 20.7 ml at follow-up; P = 0.867). On the contrary, left ventricular deformation capability significantly improved, with the real-time 3D global longitudinal strain value changing from -9.8 +/- 4.1% at baseline to -11.0 +/- 4.4% at follow-up (P = 0.018). CONCLUSIONS: Accurately assessing myocardial function by the use of 3D-STE, this study reported irrelevant early changes in left ventricular size, but a positive effect on left ventricular deformation capability following mitral valve repair with the MitraClip system. These preliminary results need to be confirmed in larger series and extended to long term follow-up. PMID- 26258718 TI - A retrospective multicenter study on long-term prevalence of chronic pain after cardiac surgery. AB - BACKGROUND: There are limited data on sternotomy as a cause of chronic postsurgical pain, mainly restricted to 1 year after surgery. AIMS: To assess the prevalence of chronic post-sternotomy pain and its interference on daily living. METHODS: In three groups of patients, a standardized telephone interview was obtained at 3 months (n = 313), 1 year (n = 313), and 3 years (n = 319) following the rehabilitation program after cardiac surgery, in 11 rehabilitation centers. Presence, site, and the severity and interference of pain on selected daily living items were assessed. RESULTS: The prevalence of pain after cardiac surgery was 35.3% in the 3-month group, 26.8% in the 1-year group, and 19.8% in the 3 year group (P < 0.0001). Pain in the 3-year group was rated as moderate to severe in one-third of the patients. In patients aged above 75 years, the prevalence of pain in the 3-month and the 3-year group was nonsignificantly different [34.2 and 29.3%, respectively (NS)]. In the 3-month group, pain was more frequent in the female (51.4%) than in the male patients (31.3%; P < 0.01); in the remaining groups, a comparable prevalence was documented. CONCLUSION: Results form this large, retrospective, multicenter survey indicated that one out of five patients still complain pain at 3 years after cardiac surgery; persistence of pain was more common in the older patients. The approach to management of chronic pain by cardiologists and cardiac surgeons should be improved. PMID- 26258719 TI - Comparison between intermediate and severe coronary stenoses and clinical outcomes of an OCT-guided PCI strategy. AB - AIMS: We compared optical coherence tomography (OCT) features of intermediate and severe coronary stenoses in patients with stable angina and acute coronary syndrome (ACS), and tested the clinical impact of an OCT-based strategy for treating intermediate stenoses. METHODS: The study enrolled 135 consecutive patients with either ACS or stable angina and a single de-novo coronary stenosis. Patients were divided into two groups: intermediate stenosis defined as quantitative coronary angiography percentage narrowing less than 70%, or presence of angiographic vessel haziness and severe stenosis with percentage narrowing more than 70%. OCT was performed to assess features of plaque vulnerability and to measure the minimal lumen area. We also appraised the 12-month rate of major adverse event (MACE) of an OCT-guided strategy of percutaneous coronary intervention (PCI) based on the presence of thrombus and/or minimal lumen area less than 3.0 mm. RESULTS: Fifty-six patients had intermediate stenoses, whilst 79 had severe stenoses. In the 'intermediate stenosis group', patients with stable angina had a lower asymmetric index (P = 0.02) and a greater calcific arc (P = 0.0001). In the 'severe stenosis group', intermediate lesions of patients with ACS exhibited a greater lipid arc as compared with patients with stable angina (P = 0.03). A higher prevalence of thin cap fibroatheroma was seen in patients with ACS of both groups. The incidence of MACE was not significantly different between patients with an intermediate stenosis who received PCI vs. optimal medical therapy on the basis of OCT findings (P = 0.26). CONCLUSIONS: Intermediate coronary stenoses showed distinctive OCT-based features according to the initial clinical presentation. The adoption of an OCT-guided PCI strategy, based on the presence of coronary thrombus and significant vessel narrowing, led to encouraging results. PMID- 26258720 TI - Aortic valve decalcification for severe aortic valve stenosis in the elderly: medium-term results. AB - AIMS: To present the results of a novel technique of aortic valve decalcification (AVD) in a consecutive population of elderly patients with severe aortic valve stenosis (AVS) and small aortic annulus. METHODS: Between January 2008 and December 2012, a consecutive series of 34 patients (mean age 80 +/- 13 years) with severe AVS were operated on using AVD. They were compared with a matched population of 68 patients (mean age 82 +/- 7 years) submitted to aortic valve replacement (AVR) with bioprosthesis. The two groups were comparable for cardiac risk factors and admission symptoms. Preoperatively, all patients presented with severe AVS, small aortic annulus (19 mm) and preserved left ventricular function. RESULTS: Thirty-day mortality was 8.8 vs. 7.5% in the AVD and AVR groups, respectively (P = 0.88). Actuarial 2 and 5-year survival rates were 80 vs. 82% and 64 vs. 78% in the AVD and AVR groups, respectively (P = 0.27). Long-term valve-related events incidence was significantly higher in the AVD group (12%) compared with that in the AVR group (4%; P = 0.01). However, in the AVD group, patients with no or mild residual AR experienced 2 and 5 years of freedom from valve-related events, which is not significantly different from the patients submitted to the AVR group (P = 0.76). After AVD, a significant increase in the aortic valve area (from 0.8 to 1.9 cm) and a parallel reduction in the mean gradient (from 40 to 12 mmHg) was observed in all patients (P = 0.01). Postoperative aortic valve area (1.9 vs. 1.26 cm), as well as mean gradient (12 vs. 21 mmHg), were significantly better in the AVD group compared with that in the AVR group (P = 0.01). CONCLUSION: In this preliminary experience, AVD seems a good therapeutic option for elderly patients with severe AVS. Further studies with longer follow-up are needed in order to confirm these preliminary results and to ascertain the valve durability over time. PMID- 26258721 TI - The prognostic value of autoantibodies against beta1-adrenoceptor and cardiac troponin-I for clinical outcomes in STEMI. AB - AIMS: The prevalence and potential role of autoantibodies against the beta1 adrenoceptor autoantibody (beta1-aab) and cardiac troponin-I (anti-cTnI) in patients with ST-elevation myocardial infarction (STEMI) are unknown. The aim of this study is to test whether beta1-aab and anti-cTnI are prevalent in STEMI patients and to investigate their prognostic value for left ventricular remodeling and clinical outcomes in STEMI patients. METHODS: This study included 491 patients with first STEMI at two centers. Serum samples were obtained. beta1 aab and anti-cTnI were detected by enzyme-linked immunoabsorbent assay. Echocardiographic assessments were performed at admission and following 1 year. The major adverse cardiovascular events (MACEs) were evaluated during a median follow-up period of 37 months. RESULTS: The positive rates of beta1-aab and anti cTnI in STEMI patients were 39.1 and 19.1%, respectively. The extent of left ventricular remodeling correlated with the presence of beta1-aab and/or anti-cTnI (double positive > single positive > double negative). Logistic regression revealed that both beta1-aab [odds ratio (OR) 2.298, 95% confidence interval (CI) 1.561-3.384, P < 0.001] and anti-cTnI (OR 2.389, 95% CI 1.460-3.909, P = 0.001) were predictive of left ventricular remodeling. Cox proportional-hazard regression revealed that beta1-aab, but not anti-cTnI, was strongly predictive of MACEs (hazard ratio 1.802, 95% CI 1.301-2.496, P < 0.001). CONCLUSION: beta1-aab and anti-cTnI were prevalent in STEMI patients. Both beta1-aab and anti-cTnI were independent predictors of left ventricular remodeling, whereas only beta1-aab was an independent predictor of MACEs. Our findings suggest that beta1-aab and anti cTnI may actively participate in the process of left ventricular remodeling after STEMI. PMID- 26258722 TI - Care quality monitoring of a ST-segment elevation myocardial infarction programme over a 5-year period. AB - AIMS: The aim of this study is to investigate the long-term impact of a prehospital ECG programme on treatment times for patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). METHODS: From January 2008 to December 2012, 213 STEMI patients transported by the Emergency Medical System (EMS) underwent primary PCI in our Hospital. The protocol included ECG tele-transmission, early activation of the cath lab and direct routing of the patient for primary PCI. Fifty-four patients referred by EMS in 2007, when ECG tele-transmission was unavailable, were used as controls. First diagnostic ECG-to-balloon time, door-to-balloon time and total ischemic time were collected for all patients. RESULTS: First diagnostic ECG-to-balloon time decreased from 125.5 min in 2007 to 104 min in the first year after implementation of the STEMI programme (2008). Successively, it declined to 81 min by the end of the study period (2012) (P < 0.0001). Door-to balloon time decreased notably from 92.5 min in 2007 to 40.5 min by the end of the study period (p < 0.0001). Total ischemic time fell from 200 min in 2007 to 170 min in 2008 and it further declined to 163.5 min in 2012 (p < 0.042). CONCLUSIONS: We report progressive improvements in times to treatment over a 5 year period in a STEMI program for patients referred by the EMS. The importance of data collection and monitoring is highlighted by our results. PMID- 26258723 TI - Effects of drug-eluting stents after rotational atherectomy: evidence from a multicenter experience. AB - AIMS: Rotational atherectomy is used as an adjuvant tool for percutaneous coronary interventions, especially in case of highly calcific atherosclerotic plaques. Subsequent drug-eluting stent (DES) implantation is common; however, there is a paucity of clinical evidence to support this practice. METHODS: From the databases of four high-volume Italian centers, we analyzed the angiographic outcome of patients who underwent rotational atherectomy in native coronary vessels followed by DES or bare metal stent (BMS) implantation. Primary study endpoint was late lumen loss at the longest available follow-up. Other analyses consisted of the evaluation of in-stent percentage diameter stenosis, binary restenosis, major adverse cardiovascular events, and stent thrombosis at angiographic control. RESULTS: Between 2006 and 2011, 672 patients with 734 lesions treated had complete angiographic follow-up and were enrolled into this study; 385 lesions were treated with DES and 349 with BMS. The average follow-up length was 9 +/- 5 months. Only a few significant differences regarding baseline clinical and angiographic characteristics were observed. Late lumen loss result significantly improved after DES implantation in comparison with BMS (0.54 +/- 0.79 vs. 1.01 +/- 1.13; P = 0.001), as well as in-stent percentage diameter stenosis (P = 0.01) and binary restenosis (P = 0.007). Major adverse cardiovascular events did not differ significantly, but showed an improved trend in the DES group, driven by a significantly lower target lesion revascularization (6.9 vs. 11.6%; P = 0.04). CONCLUSION: In a cohort of patients treated with rotational atherectomy and with complete angiographic follow-up, DES implantation is associated with improved late lumen loss over BMS. However, the DES effect in terms of angiographic endpoints seems mitigated if compared to previous studies. PMID- 26258724 TI - Utilization of stress echocardiography in patients with multivessel coronary artery disease. AB - OBJECTIVE: The purpose of this study was to evaluate the role of stress echocardiography in the risk stratification and prognosis of patients with multivessel coronary artery disease (CAD). BACKGROUND: Stress echocardiography is an established technique for diagnosis, risk stratification, and prognosis of patients with known or suspected CAD. METHODS: We evaluated 409 patients (65 +/- 10 years; 63% men) referred for stress echocardiography (45% treadmill, 55% dobutamine), who underwent stress echocardiography and coronary angiography within 3 months. All patients had multivessel CAD as defined by coronary stenosis (>=50% left main or >=70% in two or more major epicardial vessels or branches). The left ventricle was divided into 16 segments and was scored on a five-point scale of wall motion. Patients with abnormal results on stress echocardiography were defined as those with stress-induced ischemia (increase in wall motion score of >=1 grade). RESULTS: Follow-up (3.1 +/- 1.3 years) for nonfatal myocardial infarction (n = 35) and cardiac death (n = 25) was obtained. In patients with multivessel CAD, stress echocardiography effectively risk-stratified normal (no ischemia, n = 83) vs. abnormal (ischemia, n = 326) groups for cardiac events (event rate 1.9 vs. 5.4%/year; P < 0.01). Multivariable Cox proportional-hazards regression model identified stress-induced ischemia (hazard ratio 5.5, 95% confidence interval 1.9-15.9, P = 0.002) as the most significant predictor of adverse cardiac events. A stepwise Cox proportional-hazards model demonstrated significant incremental prognostic value of stress echocardiography over clinical variables, stress electrocardiography and resting left ventricular function (P < 0.0001), with the highest global chi-square value. CONCLUSIONS: In patients with angiographically significant multivessel CAD, despite normal-stress echocardiography, there was an intermediate cardiac event rate (1.9%/year); abnormal-stress echocardiography identified a high-risk group (5.4%/year); and stress echocardiography provided incremental prognostic value for risk stratification and prediction of cardiac events. PMID- 26258725 TI - Prevalence of true left bundle branch block in current practice of cardiac resynchronization therapy implantation. AB - AIMS: Accurate selection of patients with left bundle branch block (LBBB) may help increasing response to cardiac resynchronization therapy (CRT). There is no agreement on LBBB definition. The aim of the study was to investigate the prevalence of 'true-LBBB' according to Strauss in patients undergoing CRT. METHODS AND RESULTS: The study population included 414 consecutive patients (71.9% men; mean age 69.7 +/- 9.6 years), who underwent CRT according to 2010 European Society of Cardiology (ESC) guidelines. Patients were classified into three groups: traditional LBBB according to American Heart Association, LBBB according to Strauss and intraventricular conduction delay (IVCD). Subsequently, they were re-classified into classes of recommendations, according to the current 2013 ESC Guidelines. Traditional LBBB was recorded in 229 patients (55%), an LBBB according to Strauss in 153 (37%) and an IVCD in 32 (8%). Patients with an LBBB according to Strauss showed a significantly more prolonged QRS duration (P < 0.001), greater baseline end-systolic and end-diastolic volumes (P = 0.011 and P = 0.013, respectively) compared with those with IVCD. The prevalence of mid-QRS notching in at least two contiguous leads was 100% in LBBB according to Strauss; 24% in traditional LBBB and 21.9% in IVCD (P < 0.001). At multivariate analysis, PR interval less than 200 ms and QRS of at least 150 ms were independent predictors of mid-QRS notching [odds ratio (OR) 1.78; 95% confidence interval (95% CI) 1.10-2.88; P = 0.02 and OR 2.88; 95% CI 1.80-4.62;P < 0.0001]. Applying stricter criteria for LBBB according to Strauss, a significant reduction in Class I recommendation and an increase in Class II was observed (90.1 vs. 37%; P < 0.0001 and 9.9 vs. 63%; P < 0.0001). CONCLUSIONS: Applying stricter criteria, only 37% of patients undergoing CRT showed a true-LBBB according to Strauss. Accurate identification of true-LBBB may have a potential additional value in better selecting patients. PMID- 26258726 TI - Effects of functional tricuspid regurgitation on renal function and long-term prognosis in patients with heart failure. AB - AIMS: Renal dysfunction is common in heart failure. Recent evidence suggests a pivotal role for systemic venous congestion and functional tricuspid regurgitation (FTR) in the pathophysiology of renal dysfunction. We investigated the role of FTR as a determinant of renal dysfunction and a predictor of long term prognosis in chronic systolic heart failure patients. METHODS AND RESULTS: Four hundred and thirteen consecutive patients (mean age 74.2 +/- 11 years) with chronic heart failure and left ventricular ejection fraction below 50% were enrolled. The FTR severity was quantified by transthoracic echocardiography. Renal function was evaluated with the estimated glomerular filtration rate measured by the simplified Modification of Diet in Renal Disease formula. The association between moderate/severe FTR and renal dysfunction, and its impact on heart failure episodes and overall mortality were also assessed. The median follow-up was 36 months (range 1-144 months). Through multivariate analysis, the interaction between moderate/severe FTR with tricuspid annular plane systolic excursion less than 16 mm was found to be an independent determinant of renal dysfunction [odds ratio 1.2, 95% confidence interval (CI) 1.1-1.5, P = 0.04]. Moderate/severe FTR (hazard ratio 1.3, 95% CI 1.2-2.7, P = 0.02) and tricuspid annular plane systolic excursion below 16 mm (hazard ratio 1.2, 95% CI 1.0-3.7, P = 0.01) were significantly related to the heart failure episodes. Moreover, the Kaplan-Meier analysis showed a worse outcome in patients with moderate/severe FTR (log-rank test 8.6, P = 0.003). CONCLUSIONS: The combination of significant FTR and right ventricular dysfunction, but not FTR and right ventricular dysfunction alone, is independently associated with renal dysfunction. The presence of significant FTR is related to an excess event rate of heart failure and has significant impact on outcome. PMID- 26258727 TI - How do I get my article published? Insight from an EACTS luncheon. PMID- 26258728 TI - Secular Redemptions: Biopolitics by Example. AB - In this article, I analyze the practices of a group of Catholic nuns who run shelters for 'victims of human trafficking' in Italy, and are thus involved in state-funded rehabilitation programs for former foreign prostitutes. This case shows how the state and the Church are deeply implicated in each other's projects of redemption and the creation of new forms of life. In Italy, the legal model for rehabilitating foreign prostitutes is avowedly secular yet also deeply shaped by a Catholic impetus to purify sinners. At the same time, however, the nuns themselves develop an understanding of redemption as a secular life-saving project in line with the state's project of recognition, and thus inscribe their practices within the biopolitical effort to transform lives. Ultimately, I argue, leading by example becomes a specific Catholic instantiation of biopolitics that characterizes both the state's and the Church's approach to foreigners. PMID- 26258729 TI - Probing the Biomimetic Ice Nucleation Inhibition Activity of Poly(vinyl alcohol) and Comparison to Synthetic and Biological Polymers. AB - Nature has evolved many elegant solutions to enable life to flourish at low temperatures by either allowing (tolerance) or preventing (avoidance) ice formation. These processes are typically controlled by ice nucleating proteins or antifreeze proteins, which act to either promote nucleation, prevent nucleation or inhibit ice growth depending on the specific need, respectively. These proteins can be expensive and their mechanisms of action are not understood, limiting their translation, especially into biomedical cryopreservation applications. Here well-defined poly(vinyl alcohol), synthesized by RAFT/MADIX polymerization, is investigated for its ice nucleation inhibition (INI) activity, in contrast to its established ice growth inhibitory properties and compared to other synthetic polymers. It is shown that ice nucleation inhibition activity of PVA has a strong molecular weight dependence; polymers with a degree of polymerization below 200 being an effective inhibitor at just 1 mg.mL(-1). Other synthetic and natural polymers, both with and without hydroxyl-functional side chains, showed negligible activity, highlighting the unique ice/water interacting properties of PVA. These findings both aid our understanding of ice nucleation but demonstrate the potential of engineering synthetic polymers as new biomimetics to control ice formation/growth processes. PMID- 26258731 TI - Review of Fluid Therapy in Small Animal Practice (2nd edition). AB - Stephen P. DiBartola, ed.,Fluid Therapy in Small Animal Practice (2nd edition), 611 pages, (WB Saunders), ISBN: 0-7216-7739-8, reviewed by Janet Aldrich, DVM. PMID- 26258732 TI - A General Method for Solvent Exchange of Plasmonic Nanoparticles and Self Assembly into SERS-Active Monolayers. AB - We present a general route for the transfer of Au and Ag nanoparticles of different shapes and sizes, from water into various organic solvents. The experimental conditions for each type of nanoparticles were optimized by using a combination of thiolated poly(ethylene glycol) and a hydrophobic capping agent, such as dodecanethiol. The functionalized nanoparticles were readily transferred into organic dispersions with long-term stability (months). Such organic dispersions efficiently spread out on water, leading to self-assembly at the air/liquid interface into extended nanoparticle arrays which could in turn be transferred onto solid substrates. The dense close packing in the obtained nanoparticle monolayers results in extensive plasmon coupling, rendering them efficient substrates for surface-enhanced Raman scattering spectroscopy. PMID- 26258735 TI - A New ELOVL4 Mutation in a Case of Spinocerebellar Ataxia With Erythrokeratodermia. PMID- 26258730 TI - A meta-analytic review of religious or spiritual involvement and social health among cancer patients. AB - Religion and spirituality (R/S) play an important role in the daily lives of many cancer patients. There has been great interest in determining whether R/S factors are related to clinically relevant health outcomes. In this meta-analytic review, the authors examined associations between dimensions of R/S and social health (eg, social roles and relationships). A systematic search of the PubMed, PsycINFO, Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature databases was conducted, and data were extracted by 4 pairs of investigators. Bivariate associations between specific R/S dimensions and social health outcomes were examined in a meta-analysis using a generalized estimating equation approach. In total, 78 independent samples encompassing 14,277 patients were included in the meta-analysis. Social health was significantly associated with overall R/S (Fisher z effect size = .20; P < .001) and with each of the R/S dimensions (affective R/S effect size = 0.31 [P < .001]; cognitive R/S effect size = .10 [P < .01]; behavioral R/S effect size = .08 [P < .05]; and 'other' R/S effect size = .13 [P < .001]). Within these dimensions, specific variables tied to social health included spiritual well being, spiritual struggle, images of God, R/S beliefs, and composite R/S measures (all P values < .05). None of the demographic or clinical moderating variables examined were significant. Results suggest that several R/S dimensions are modestly associated with patients' capacity to maintain satisfying social roles and relationships in the context of cancer. Further research is needed to examine the temporal nature of these associations and the mechanisms that underlie them. PMID- 26258736 TI - Successful Antiviral Treatment of Giant Cell Arteritis and Takayasu Arteritis. PMID- 26258737 TI - Fragile X Tremor Ataxia Syndrome With Rapidly Progressive Myopathy. PMID- 26258738 TI - Subthalamic Nucleus Deep Brain Stimulation in Parkinson Disease. PMID- 26258739 TI - Subthalamic Nucleus Deep Brain Stimulation in Parkinson Disease--Reply. PMID- 26258740 TI - Diabetes Mellitus and Cognitive Resilience. PMID- 26258742 TI - Error in Byline. Neuroinflammation in Temporal Lobe Epilepsy Measured Using Positron Emission Tomographic Imaging of Translocator Protein. PMID- 26258741 TI - Diabetes Mellitus and Cognitive Resilience--Reply. PMID- 26258743 TI - Error in Figure. Comparison of Switch to Fingolimod or Interferon Beta/Glatiramer Acetate in Active Multiple Sclerosis. PMID- 26258744 TI - Redundant Information in Text and Incorrect Reference. Association of a Novel ACTA1 Mutation With a Dominant Progressive Scapuloperoneal Myopathy in an Extended Family. PMID- 26258746 TI - Chimeric Nanoparticle: A Platform for Simultaneous Targeting of Phosphatidylinositol-3-Kinase Signaling and Damaging DNA in Cancer Cells. AB - Phosphatidylinositol-3-kinase (PI3K) signaling has been hijacked in different types of cancers. Hence, PI3K inhibitors have emerged as novel targeted therapeutics in cancer treatment as mono and combination therapy along with other DNA damaging drugs. However, targeting PI3K signaling with small molecules leads to the emergence of drug resistance and severe side effects to the cancer patients. To address these, we have developed a biocompatible, biodegradable cholesterol-based chimeric nanoparticle (CNP), which can simultaneously load PI103, doxorubicin, and cisplatin in a controlled ratiometric manner. Size, shape, and morphology of these CNPs were characterized by dynamic light scattering (DLS), field-emission scanning electron microscopy (FESEM), atomic force microscopy (AFM), and transmission electron microscopy (TEM). Increased amounts of PI103, doxorubicin, and cisplatin were released from CNPs through controlled and continuous manner over 120 h at pH = 5.5 compared to neutral pH. The CNPs showed much enhanced in vitro cytotoxicity in HeLa, HL60, MCF7, and MDA MB-231 cancer cells compared to a free drug cocktail at 24 and 48 h by inducing apoptosis. Confocal laser scanning microscopy (CLSM) imaging revealed that indeed these CNPs were internalized into subcellular lysosomes through endocytosis in a time dependent mode over 6 h and retained inside for 48 h in HeLa, MDA-MB-231, and MCF7 cells. These CNPs showed their efficacy by damaging DNA and inhibiting Akt as a downstream modulator of PI3K signaling in HeLa cervical cancer cells. These CNPs have the potential to open up new directions in next-generation nanomedicine by simultaneous targeting of multiple oncogenic signaling pathways and inducing DNA damage for augmented therapeutic outcome by reducing toxic side effects and overcoming drug resistance. PMID- 26258748 TI - Oral fumaric acid esters for psoriasis. AB - BACKGROUND: Psoriasis is a chronic inflammatory skin condition that can markedly reduce life quality. Several systemic therapies exist for moderate to severe psoriasis, including oral fumaric acid esters (FAE). These contain dimethyl fumarate (DMF), the main active ingredient, and monoethyl fumarate. FAE are licensed for psoriasis in Germany but used off-licence in many countries. OBJECTIVES: To assess the effects and safety of oral fumaric acid esters for psoriasis. SEARCH METHODS: We searched the following databases up to 7 May 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (Issue 4, 2015), MEDLINE (from 1946), EMBASE (from 1974), and LILACS (from 1982). We searched five trials registers and checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials. We handsearched six conference proceedings that were not already included in the Cochrane Skin Group Specialised Register. SELECTION CRITERIA: Randomised controlled trials (RCTs) of FAE, including DMF monotherapy, in individuals of any age and sex with a clinical diagnosis of psoriasis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Primary outcomes were improvement in Psoriasis Area and Severity Index (PASI) score and the proportion of participants discontinuing treatment due to adverse effects. MAIN RESULTS: We included 6 studies (2 full reports, 2 abstracts, 1 brief communication, and 1 letter), with a total of 544 participants. Risk of bias was unclear in several studies because of insufficient reporting. Five studies compared FAE with placebo, and one study compared FAE with methotrexate. All studies reported data at 12 to 16 weeks, and we identified no longer-term studies. When FAE were compared with placebo, we could not perform meta-analysis for the primary outcome of PASI score because the three studies that assessed this outcome reported the data differently, although all studies reported a significant reduction in PASI scores with FAE. Only 1 small study designed for psoriatic arthritis reported on the other primary outcome of participants discontinuing treatment due to adverse effects (2 of 13 participants on FAE compared with none of the 14 participants on placebo; risk ratio (RR) 5.36, 95% confidence interval (CI) 0.28 to 102.1; 27 participants; very low-quality evidence). However, these findings are uncertain due to indirectness and a very wide confidence interval. Two studies, containing 247 participants and both only reported as abstracts, allowed meta-analysis for PASI 50, which showed superiority of FAE over placebo (RR 4.55, 95% CI 2.80 to 7.40; low-quality evidence), with a combined PASI 50 of 64% in those given FAE compared with a PASI 50 of 14% for those on placebo, representing a number needed to treat to benefit of 2. The same studies reported more participants achieving PASI 75 with FAE, but we did not pool the data because of significant heterogeneity; none of the studies measured PASI 90. One study reported significant improvement in participants' quality of life (QoL) with FAE, measured with Skindex-29. However, we could not compute the mean difference because of insufficient reporting in the abstract. More participants experienced adverse effects, mainly gastrointestinal disturbance and flushing, on FAE (RR 4.72, 95% CI 2.45 to 9.08; 1 study, 99 participants; moderate-quality evidence), affecting 76% of participants given FAE and 16% of the placebo group (representing a number needed to treat to harm of 2). The other studies reported similar findings or did not report adverse effects fully.One study of 54 participants compared methotrexate (MTX) with FAE. PASI score at follow-up showed superiority of MTX (mean Difference (MD) 3.80, 95% CI 0.68 to 6.92; 51 participants; very low-quality evidence), but the difference was not significant after adjustment for baseline disease severity. The difference between groups for the proportion of participants who discontinued treatment due to adverse effects was uncertain because of imprecision (RR 0.19, 95% CI 0.02 to 1.53; 1 study, 51 participants; very low-quality evidence). Overall, the number of participants experiencing common nuisance adverse effects was not significantly different between the 2 groups, with 89% of the FAE group affected compared with 100% of the MTX group (RR 0.89, 95% CI 0.77 to 1.03; 54 participants; very low-quality evidence). Flushing was more frequent in those on FAE, with 13 out of 27 participants affected compared with 2 out of 27 given MTX. There was no significant difference in the number of participants who attained PASI 50, 75, and 90 in the 2 groups (very low-quality evidence) whereas this study did not measure the effect of treatments on QoL. The included studies reported no serious adverse effects of FAE and were too small and of limited duration to provide evidence about rare or delayed effects. AUTHORS' CONCLUSIONS: Evidence suggests that FAE are superior to placebo and possibly similar in efficacy to MTX for psoriasis; however, the evidence provided in this review was limited, and it must be noted that four out of six included studies were abstracts or brief reports, restricting study reporting. FAE are associated with nuisance adverse effects, including flushing and gastrointestinal disturbance, but short-term studies reported no serious adverse effects. PMID- 26258747 TI - Cytoprotective effects of grape seed extract on human gingival fibroblasts in relation to its antioxidant potential. AB - Cytoprotective effects of short-term treatment with grape seed extract (GSE) upon human gingival fibroblasts (hGFs) were evaluated in relation to its antioxidant properties and compared with those of a water-soluble analog of vitamin E: trolox (Tx). GSE and Tx showed comparable antioxidant potential in vitro against di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (DPPH; a stable radical), hydroxyl radical (*OH), singlet oxygen (1O2), and hydrogen peroxide (H2O2). Pretreatment or concomitant treatment with GSE for 1 min protected hGFs from oxidative stressors, including H2O2, acid-electrolyzed water (AEW), and 1O2, and attenuated the intracellular formation of reactive oxygen species induced by H2O2 and AEW. Tx also reduced the H2O2- and AEW-induced intracellular formation of reactive oxygen species, but showed no cytoprotective effects on hGFs exposed to H2O2, AEW, or 1O2. These results suggest that the cytoprotective effects of GSE are likely exerted independently of its antioxidant potential. PMID- 26258749 TI - A head to head comparison of nine tools predicting non-sentinel lymph node status in sentinel node positive breast cancer women. AB - BACKGROUND AND OBJECTIVES: This study was conducted to evaluate the performance of available tools predicting non-sentinel lymph node (non-SLN) status in women with SLN positive breast cancer and to see if they can be safely used in everyday clinical practice. METHODS: Data of 220 women with breast cancer who underwent a SLN biopsy at the Maxima Medical Centre between 2000-2008 were analysed. Tools evaluated were: the models from Memorial Sloan Kettering Cancer Centre, Stanford, Mayo, Cambridge, Gur, and MOU, and the scores from Saidi, Tenon, and MDA. Model performance was assessed using calibration, discrimination and Nagelkerke's explained variation. RESULTS: The MSKCC nomogram showed best overall performance with best discrimination (AUC 0.69), second best calibration, and highest explained variation (31%). The 10% low risk threshold led to defining only 22% (38/176) of the women as being low risk while in fact 66% (116/176) were non-SLN negative. The false negative rate was 13% (5/38). CONCLUSIONS: Current models for predicting non-SLN metastases in SLN positive breast cancer are not yet ready for implementation in general practice. Further research efforts should improve model performance in selecting patients or perhaps find a role in support in the paradigm shift to a "treat none unless" approach. PMID- 26258750 TI - Fabrication of aligned, porous and conductive fibers and their effects on cell adhesion and guidance. AB - The potential applications of aligned, conductive electrospun fibers have been widely studied in anisotropic tissue regeneration. In this study, aligned porous poly L-lactic acid fibers were obtained with electrospinning, then polypyrrole nanoparticles (PPy NPs) were coated onto the porous fibers with oxidation polymerization to prepare electrically conductive fibers with about 1.24 MUm of diameter, and their surface conductivity was about 50 mS. The results of L929 cell test showed that more than 55% of cells grew along the aligned porous fiber axis, confirming that the cell guidance of aligned porous fibers was better than that of non-porous fibers. The results of differentiated PC12 cells on porous fibers showed that the alignment degree of neurite outgrowth and average neurite length of the cells were 84% and 111 MUm, respectively, which were larger than those on the non-porous fibers. A primary mechanism was proposed to explain effect of these pores on cell/neurite adhesion and orientation along the aligned porous fibers. PMID- 26258751 TI - Imprinted nanospheres based on precipitation polymerization for the simultaneous extraction of six urinary benzene metabolites from urine followed by injector port silylation and gas chromatography-tandem mass spectrometric analysis. AB - In the present communication, uniformly sized molecularly imprinted polymer (MIP) as nanospheres were synthesized based on precipitation polymerization using dual template imprinting approach and used it as sorbent for solid phase extraction of six urinary benzene metabolites (UBMs). This approach in combination with injector port silylation (IPS) has been used for the quantitative determination of these UBMs by gas chromatography-tandem mass spectrometry. The MIP was synthesized by using t,t-muconic acid (t,t-MA) and 1,2,4-trihydroxybenzene (THB) as templates, methacrylic acid (MAA) as a monomer, ethyleneglycoldimethacrylate (EGDMA) as crosslinker, acetonitrile and dimethylsulphoxide as a porogen and azobisisobutyronitrile (AIBN) as an initiator. The factors affecting the performance of polymer and IPS were investigated and optimized for the simultaneous determination of UBMs in urine. Binding study of imprinted and non imprinted polymer (NIP) shows that, MIP possesses higher affinity in comparison to NIP for these analytes. Under the optimum conditions, the method developed was found to be linear with regression coefficients falls in the range of 0.9721 0.9988 for all the analyzed metabolites. The percent recovery of the metabolites analyzed in urine was found to be in the range of 76-89%, while the limit of detection and limit of quantification were found to be in the range of 0.9 9.1ngmL(-1) and 2.8-27ngmL(-1) respectively. The validated method was successfully applied to the real urine samples collected from different groups (kitchen workers, smokers and petroleum workers) and found that the developed method has been promising applications in the routine analysis of urine samples of benzene exposed population. PMID- 26258752 TI - Ki-67 Membranous Staining: Biologically Relevant or an Artifact of Multiplexed Immunofluorescent Staining. AB - In the process of developing a multiplex of 8 common breast cancer biomarkers (Her2/neu, estrogen receptor, progesterone receptor, Ki-67, aldehyde dehydrogenase-1, NaK-ATPase, cytokeratin 8/18, and myosin smooth muscle) on a single formalin-fixed paraffin-embedded slide using a sequential staining, imaging, and dye bleaching technology developed by General Electric Company, membranous Ki-67 staining was observed and colocalized with Her2/neu staining. Using immunohistochemistry as gold standards, we discovered that membranous Ki-67 was an artifact caused by the binding of cyanine 5-conjugated rabbit polyclonal Ki-67 antibody to a secondary cyanine 3-conjugated donkey anti-rabbit antibody which was previously applied and bound to rabbit Her2/neu antibody in our multiplexing experiment. After blocking with rabbit serum, a successful protocol for 8 biomarker multiplexing without cross-reactivity of antibodies from the same species was developed. PMID- 26258753 TI - Immunohistochemical Evaluation of Leptin Expression in Wound Healing: A Clue to Exuberant Scar Formation. AB - Leptin has been recognized as an important factor for promoting normal cutaneous wound healing. The aim of this work was to explore leptin expression in keloid and hypertrophic scars (HS) compared with surgical scars and normal skin. The relationship of this expression with clinicopathologic parameters of studied cases was also evaluated. Using immunohistochemical techniques, leptin was analyzed in skin biopsies of 60 nonobese subjects without metabolic syndrome who presented with keloids (20), HS (20), and surgical scars (20). Twenty normal skin samples, from age-matched, sex-matched, and body mass index-matched subjects, were enrolled as a control group. Leptin showed positive immunoreactivity in epidermis in all cases of surgical scars and keloids and in 75% of HS cases. Dermal expression in fibroblasts, inflammatory cells, and endothelial cells was positive in all cases of surgical scars and keloids and in 70% of HS cases. Leptin was overexpressed in keloids and HS compared with normal skin in epidermis (P<0.001 for both) and dermis (P<0.001 for both) and to surgical scars both in epidermis (P=0.0006, P=0.01, respectively) and dermis (P=0.0001, P=0.001, respectively). Higher leptin H score was significantly associated with older age (P=0.02) and positive family history (P=0.002) in keloid cases and with axial site in keloid and HS cases (P=0.001, P=0.02, respectively). Significant positive correlation was noted between epidermal and dermal leptin H scores in keloids (r=+0.37, P=0.04) and HS (r=+0.39, P=0.02). This may be due to epithelial mesenchymal interactions in scar pathogenesis. In conclusion, in situ leptin overexpression may increase the possibility of keloid and HS occurrence through altered cytokine production and prolonged healing phases with excessive deposition and delayed collagen degradation. This may open an avenue for research for new therapeutic modalities based on its inhibition. PMID- 26258754 TI - Primary Intestinal Diffuse Large B-cell Lymphoma in Taiwan Showed a Relative Higher Rate of Perforation and EBV Association. AB - We retrospectively investigated 59 surgically resected primary intestinal diffuse large B-cell lymphomas (PI-DLBCL) including 31 males and 28 females with a median age of 66. Eleven (19%) tumors were perforated at presentation; 8 (14%) were multicentric. Ileum (n=24; 43%) and ileocecum (n=17; 30%) were most frequently involved. Twenty-one (36%) patients did not receive chemotherapy or radiotherapy including 6 with perforation and died in 0.2 to 7 months. The 1-, 2-, and 5-year overall survival rates were 68.4%, 56.5%, and 50.0%, respectively. Seven (12%) of 59 cases were positive for Epstein-Barr virus (EBV) by in situ hybridization. IGH, BCL2, BCL6, and MYC foci were rearranged in 22%, 3%, 17%, and 7% cases, respectively, with 14% exhibiting gain/amplification at the MYC locus. Perforation (P=0.009), high ECOG PS (>=2) (P=0.018), and no adjuvant chemotherapy (P<0.001) were poor prognostic factors but not immunophenotype including co expression of bcl-2 and myc, EBV status, or chromosomal aberrations. Perforation and chemotherapy remained significant by multivariate analysis. PI-DLBCL in Taiwan carried a relatively higher rate of perforation, lower frequency of germinal center B-cell phenotype, and higher EBV association as compared with studies from other geographic areas. Furthermore, perforation was a poor prognostic factor. PMID- 26258755 TI - Rheb/mTOR/p70s6k Cascade and TFE3 Expression in Conventional and Sclerosing PEComas of the Urinary Tract. AB - Perivascular epithelioid cell tumors (PEComas) are rarely found in the urinary tract. The clinicopathologic characteristics of 10 cases, retrospectively collected from 5 medical institutions in 3 different European countries, are presented in this study. Male/female ratio was 3:7 and the average age at diagnosis was 62.7 years. Nine cases were sporadic and 1 showed germline mutation of the TSC2 gene. Eight cases were located in the kidney, 1 in the left adrenal and 1 in the right ureter. All of the patients were alive and free of disease at the time of last contact (mean follow-up, 14.1 mo). Four cases displayed a conventional morphology and 6 showed a prominent sclerotic stroma. By immunohistochemistry, melanocytic markers were consistently expressed, especially HMB-45 (10 cases), MiTF (9 cases), and Melan-A (6 cases). Desmin was expressed in 6 cases; 2 cases were positive for CD117; a single case showed TFE3 expression. pMAPK, mTOR, and pAKT demonstrated variable immunostaining with focal positivity in 7, 4, and 2 cases, respectively. Cytokeratins were repeatedly negative in all cases. PEComas in the urinary tract, especially in the renal region, may show a relatively high frequency of the sclerosing histologic subtype. Knowledge of the distinct histology and immunohistochemical profile is vital to correctly diagnose this rare entity. PMID- 26258756 TI - Reduced miR-512 and the Elevated Expression of Its Targets cFLIP and MCL1 Localize to Neurons With Hyperphosphorylated Tau Protein in Alzheimer Disease. AB - The cause for the neurofibrillary tangles and plaques in Alzheimer disease likely relates to an abnormal accumulation of their key components, which include beta amyloid and hyperphosphorylated tau protein. We segregated Alzheimer brain sections from people with end-stage disease into those with abundant hyperphosphorylated tau protein and those without and compared each to normal brains for global microRNA patterns. A significant reduced expression of several microRNAs, including miR-512, was evident in the Alzheimer brain sections with abundant hyperphosphorylated tau. Immunohistochemistry documented that 2 known targets of microRNA-512, cFLIP and MCL1, were significantly over expressed and each colocalized to neurons with the abnormal tau protein. Analysis for apoptosis including activated caspase-3, increased caspase-4 and caspase-8, apoptosis initiating factor, APAF-1 activity, and the TUNEL assay was negative in the areas where neurons showed hyperphosphorylated tau. MCM2 expression, a marker of neuroprogenitor cells, was significantly reduced in the Alzheimer sections that contained the hyperphosphorylated tau. These results suggest that a basic defect in Alzheimer disease may be the reduced microRNA-driven increased expression of proteins that may alter the apoptotic/antiapoptotic balance of neurons. This, in turn, could lead to the accumulation of key Alzheimer proteins such as hyperphosphorylated tau that ultimately prevent normal neuronal function and lead to disease symptomatology. PMID- 26258757 TI - Insulin-like Growth Factor II Messenger RNA-binding Protein 3 in Salivary Gland Tumors. AB - Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is strongly expressed in malignant tumors and has been associated with their aggressive behavior. The aim of this study was to evaluate the presence of IMP3 in a series of salivary gland tumors. The sample consisted of 9 pleomorphic adenomas (PA), 14 adenoid cystic carcinomas (ACC), and 13 mucoepidermoid carcinomas (MEC) that were investigated by immunohistochemical technique. All cases of PA and MEC were positive for IMP3 particularly in the cytoplasm. PA showed 4 cases as high expression and 6 as low expression. MEC showed 10 cases as low expression and 3 as high expression. For ACC, 4 cases were high expression, whereas 6 cases were low expression. No significant difference was observed between tumors (P>0.05, Fisher's test) when both scores of IMP3 were compared. This study showed that MEC seems to be more sensitive to IMP3 than ACC and provided an insight into this protein in salivary gland tumors. Furthermore, although IMP3 is not a specific diagnostic marker to distinguish the tumors studied, it seems to mediate cell adhesion and migration in these tumors. Further studies should be performed to better understand the IMP3 biology in salivary gland tumors. PMID- 26258758 TI - Novel Method Probe-based Real-Time PCR to Detect 2 Single-Nucleotide Polymorphisms Close to Each Other: HFE Hemochromatosis Gene Model. AB - Hereditary hemochromatosis is known as the most common genetic disorder among individuals of European genetic background. It is possible to find 2 mutations closely placed in the HFE gene (H63D and S65C) and this proximity can cause errors when genotyped by real-time polymerase chain reaction (PCR) genotyping assay. The aim of this study was to develop a hydrolysis probe-based PCR assay for detection of the H63D and S65C mutations without interference from on each other. Herein the study involved the standardization of an improvement of the real-time PCR 5' nuclease assay to detect the desired mutations close placed using a same probe system. The assay analytical properties performances were tested, including the primers selectivity and detection limits. Also, the interexaminer reproducibility and repeatability of assay were estimated in 30 blood samples. Others 153 results of samples were compared with reference method (PCR_RFLP) and the accordance of the results evaluated by Fleiss' kappa method. The results of variation of interexaminer reproducibility and repeatability of assay were not statistically relevant (P<0.001). The comparison between the 2 methods by Fleiss' kappa analysis showed that 5' nuclease assay identified the H63D and S65C haplotype as well as the reference method in all 153 tested samples. Our results showed that novel method probe-based real-time PCR were capable to detect 2 adjacent polymorphisms without errors in genotyping. PMID- 26258760 TI - Quantum Transport Detected by Strong Proximity Interaction at a Graphene-WS2 van der Waals Interface. AB - Magnetotransport measurements demonstrate that graphene in a van der Waals heterostructure is a sensitive probe of quantum transport in an adjacent WS2 layer via strong Coulomb interactions. We observe a large low-field magnetoresistance (? e(2)/h) and a -ln T temperature dependence of the resistance. In-plane magnetic field resistance indicates the origin is orbital and nonclassical. We demonstrate a strong electron-hole asymmetry in the mobility and coherence length of graphene demonstrating the presence of localized Coulomb interactions with ionized donors in the WS2 substrate, which ultimately leads to screening as the Fermi level of graphene is tuned toward the conduction band of WS2. This leads us to conclude that graphene couples to quantum localization processes in WS2 via the Coulomb interaction and results in the observed signatures of quantum transport. Our results show that theoretical descriptions of the van der Waals interface should not ignore localized strong correlations. PMID- 26258761 TI - Attitudes to Alzheimer's disease testing of Australian general practice patients: a cross-sectional questionnaire-based study. AB - OBJECTIVE: In view of proposed screening for presymptomatic Alzheimer's disease (AD) with advanced imaging, and blood and cerebral spinal fluid analysis, we aimed to establish levels, and associations, of acceptance of AD testing modalities by general practice patients. METHODS: A cross-sectional questionnaire based study of consecutive patients (aged 50 years and over) of general practices of an Australian practice-based research network was used. The questionnaire elicited demographic data and attitudes to screening for other diseases and included the screening acceptance domain of the Perceptions Regarding Investigational Screening for Memory in Primary Care (PRISM-PC) instrument. This assesses receptivity to modalities of testing for AD: short questionnaire, blood test, cerebral imaging, and annual physician examination. Reflecting speculation of possible future AD diagnostic methods, an item regarding testing cerebral spinal fluid was also included. Associations of PRISM-PC scores were analyzed with multiple linear regression. RESULTS: Of 489 participants (response rate 87%), 66.2% would like to know if they had AD. Participants were more accepting of testing modalities that were noninvasive or familiar (questionnaire, physician's examination, and blood test) as opposed to cerebral imaging or lumbar puncture. Attitudes to AD testing are influenced by a positive attitude to disease screening in general. Patients with a self-perceived higher risk of AD were less accepting of testing, as were participants with an educational level of junior high school (10 school years) or less. CONCLUSIONS: This study demonstrates that a majority of patients would like to know if they have AD. Acceptability of testing modalities, however, varies. Noninvasive, familiar methods are more acceptable. PMID- 26258762 TI - A fungal monooxygenase-derived jasmonate attenuates host innate immunity. AB - Distinct modifications fine-tune the activity of jasmonic acid (JA) in regulating plant growth and immunity. Hydroxylated JA (12OH-JA) promotes flower and tuber development but prevents induction of JA signaling, plant defense or both. However, biosynthesis of 12OH-JA has remained elusive. We report here an antibiotic biosynthesis monooxygenase (Abm) that converts endogenous free JA into 12OH-JA in the model rice blast fungus Magnaporthe oryzae. Such fungal 12OH-JA is secreted during host penetration and helps evade the defense response. Loss of Abm in M. oryzae led to accumulation of methyl JA (MeJA), which induces host defense and blocks invasive growth. Exogenously added 12OH-JA markedly attenuated abmDelta-induced immunity in rice. Notably, Abm itself is secreted after invasion and most likely converts plant JA into 12OH-JA to facilitate host colonization. This study sheds light on the chemical arms race during plant-pathogen interaction, reveals Abm as an antifungal target and outlines a synthetic strategy for transformation of a versatile small-molecule phytohormone. PMID- 26258763 TI - An excess of catalytically required motions inhibits the scavenger decapping enzyme. AB - The scavenger decapping enzyme hydrolyzes the protective 5' cap structure on short mRNA fragments that are generated from the exosomal degradation of mRNAs. From static crystal structures and NMR data, it is apparent that the dimeric enzyme has to undergo large structural changes to bind its substrate in a catalytically competent conformation. Here we studied the yeast enzyme and showed that the associated opening and closing motions can be orders of magnitude faster than the catalytic turnover rate. This excess of motion is induced by the binding of a second ligand to the enzyme, which occurs at high substrate concentrations. We designed a mutant that disrupted the allosteric pathway that links the second binding event to the dynamics and showed that this mutant enzyme is hyperactive. Our data reveal a unique mechanism of substrate inhibition in which motions that are required for catalytic activity also inhibit efficient turnover when they are present in excess. PMID- 26258764 TI - SH3 domain of c-Src governs its dynamics at focal adhesions and the cell membrane. AB - We studied the role of the Src SH3 domain in its dynamics at the cell membrane using site-directed mutagenesis and live cell imaging. Physiologically, cell proliferation and migration require the expression of Src family kinases. Hyperactivation of Src molecules has been detected in various cancer cells. Although the activation mechanism of Src has been intensively studied, the dynamics of Src at the cell membrane are still unclear. Although Src molecules also exist at various cellular locations, we found that activated Src molecules are mainly localized at peripheral cell adhesion sites. Src phosphorylation status and subdomain conformations are thought to regulate Src activation and translocation. In this study, we analyzed the single-molecule dynamics of wild type Src and SH2- and SH3-mutated Src at the cell membrane. Introducing mutations in the SH3 domain resulted in reduced Src motility at the cell membrane, both inside and outside of focal adhesions. Disruption of the actin cytoskeleton resulted in less diffusive Src movement at the cell membrane. We demonstrate that, inside focal adhesions, the SH3 domain enhanced dissociation of Src from the adhesion site and disruption of the SH3 domain altered the distribution of Src at the cell membrane. Inside focal adhesions, kinase activity of Src was essential for the Src mobility reduction by SH3 domain mutation, suggesting that rapid mobility of Src at focal adhesions mediated by the SH3 domain is catalytic activity-dependent. These findings show that the SH3 domain of Src governs the dynamics of Src at the cell membrane and may be involved in rapid signal transduction in cells. PMID- 26258765 TI - New Therapies in the Treatment of High Cholesterol: An Argument to Return to Goal Based Lipid Guidelines. PMID- 26258766 TI - Omental adipose tissue fibrosis and insulin resistance in severe obesity. AB - BACKGROUND/OBJECTIVES: The unresolved chronic inflammation of white adipose tissue (WAT) in obesity leads to interstitial deposition of fibrogenic proteins as reparative process. The contribution of omental adipose tissue (oWAT) fibrosis to obesity-related complications remains controversial. The aim of our study was to investigate whether oWAT fibrosis may be related to insulin resistance in severely obese population. SUBJECTS/METHODS: Forty obese subjects were studied by glucose clamp before undergoing bariatric surgery and thus stratified according to insulin resistance severity (M-value). From the first (Group B: n=13; M=1.9+/ 0.7 mg kg(-1) min(-1)) and the highest (Group A: n=14; M=4.5+/-1.4 mg kg(-1) min( 1)) M-value tertiles, which were age-, waist- and body mass index-matched, oWAT samples were then obtained.Gene expression of collagen type I, III and VI, interleukin-6, profibrotic mediators (transforming growth factor (TGF)-beta1, activin A, connective tissue growth factor), hypoxia inducible factor-1alpha (HIF 1alpha) and macrophage (CD68, monocyte chemotactic protein (MCP)-1, CD86, CD206, CD150) markers were analyzed by quantitative reverse transcription PCR. Adipocyte size and total fibrosis were assessed by histomorphometry techniques. RESULTS: Fibrosis at morphological level resulted significantly greater in Group B compared with Group A, although collagens gene expression did not differ. Notably, collagen VI messenger RNA significantly correlated with collagen I, collagen III, HIF-1alpha, TGF-beta1, CD68, MCP-1 and CD86 transcription levels, supporting their relation with fibrosis development. CONCLUSIONS: In conclusion, we show for the first time that human oWAT fibrosis in severe obesity is consistent with a higher degree of insulin resistance measured by glucose clamp. Therefore, collagen deposition could represent a maladaptive mechanism contributing to obesity-related metabolic complications. PMID- 26258768 TI - Self-consistent method for quantifying indium content from X-ray spectra of thick compound semiconductor specimens in a transmission electron microscope. AB - Based on Monte Carlo simulations of X-ray generation by fast electrons we calculate curves of effective sensitivity factors for analytical transmission electron microscopy based energy-dispersive X-ray spectroscopy including absorption and fluorescence effects, as a function of Ga K/L ratio for different indium and gallium containing compound semiconductors. For the case of InGaN alloy thin films we show that experimental spectra can thus be quantified without the need to measure specimen thickness or density, yielding self-consistent values for quantification with Ga K and Ga L lines. The effect of uncertainties in the detector efficiency are also shown to be reduced. PMID- 26258767 TI - Relation of intelligence quotient and body mass index in preschool children: a community-based cross-sectional study. AB - OBJECTIVE: Overweight and obesity in children is a global problem. Besides physical effects, obesity has harmful psychological effects on children. METHODS: We carried out cross-sectional community-based study to investigate the relation between body mass index (BMI) and cognitive functioning in preschool children. Thirteen socioeconomical elements of 1151 children were measured and analyzed based on their intelligence quotient (IQ) test results. Thirteen out of 33 provinces were selected randomly, and schools were selected as clusters in rural and urban areas. Descriptive statistics, t-test, analysis of variance and regression were used when appropriate. RESULTS: Our analysis showed that IQ was associated with household income, place of residence, delivery type, type of infant feeding and father's and mother's education level (P<0.001 for all). Using penalized linear regression for eliminating the impact of confounding factor, our study shows that, living in metropolitan (beta=2.411) and urban areas (beta=2.761), the level of participants' father's education (beta=5.251) was positively and BMI (beta=-0.594) was negatively related with IQ test results.ConclusionsThe findings of the present study showed that a lower IQ score is associated with higher BMI. However, this relation appears to be largely mediated when the socioeconomic status was considered. PMID- 26258770 TI - Fatal Injury Caused by a Ram (Ovis Aries) Attack. AB - Animal-inflicted injuries to humans are a major public health problem around the world resulting in great morbidity, money loss, and mortality. They are related to wild and domestic animals alike. Animals can cause injuries by various mechanisms--biting, stinging, crushing, goring, stomping, butting, kicking, pecking, etc. We present a case of a ram's attack with fatal consequences. A 4 year-old, 120 kg jezersko-solcava breed ram with prior history of aggressive behavior inflicted multiple injuries to his 83-year-old owner, who died in the hospital a few hours later due to severe blunt force injuries sustained in the attack. The autopsy revealed the cause of death to be multiple injuries of the thorax and the head. Sheep, even though they are not considered aggressive or large farm animals such as cattle and horses, can inflict serious injuries with devastating results. PMID- 26258769 TI - Adiabatic far-field sub-diffraction imaging. AB - The limited resolution of a conventional optical imaging system stems from the fact that the fine feature information of an object is carried by evanescent waves, which exponentially decays in space and thus cannot reach the imaging plane. We introduce here an adiabatic lens, which utilizes a geometrically conformal surface to mediate the interference of slowly decompressed electromagnetic waves at far field to form images. The decompression is satisfying an adiabatic condition, and by bridging the gap between far field and near field, it allows far-field optical systems to project an image of the near field features directly. Using these designs, we demonstrated the magnification can be up to 20 times and it is possible to achieve sub-50 nm imaging resolution in visible. Our approach provides a means to extend the domain of geometrical optics to a deep sub-wavelength scale. PMID- 26258771 TI - Eutrophication effects on greenhouse gas fluxes from shallow-lake mesocosms override those of climate warming. AB - Fresh waters make a disproportionately large contribution to greenhouse gas (GHG) emissions, with shallow lakes being particular hot spots. Given their global prevalence, how GHG fluxes from shallow lakes are altered by climate change may have profound implications for the global carbon cycle. Empirical evidence for the temperature dependence of the processes controlling GHG production in natural systems is largely based on the correlation between seasonal temperature variation and seasonal change in GHG fluxes. However, ecosystem-level GHG fluxes could be influenced by factors, which while varying seasonally with temperature are actually either indirectly related (e.g. primary producer biomass) or largely unrelated to temperature, for instance nutrient loading. Here, we present results from the longest running shallow-lake mesocosm experiment which demonstrate that nutrient concentrations override temperature as a control of both the total and individual GHG flux. Furthermore, testing for temperature treatment effects at low and high nutrient levels separately showed only one, rather weak, positive effect of temperature (CH4 flux at high nutrients). In contrast, at low nutrients, the CO2 efflux was lower in the elevated temperature treatments, with no significant effect on CH4 or N2 O fluxes. Further analysis identified possible indirect effects of temperature treatment. For example, at low nutrient levels, increased macrophyte abundance was associated with significantly reduced fluxes of both CH4 and CO2 for both total annual flux and monthly observation data. As macrophyte abundance was positively related to temperature treatment, this suggests the possibility of indirect temperature effects, via macrophyte abundance, on CH4 and CO2 flux. These findings indicate that fluxes of GHGs from shallow lakes may be controlled more by factors indirectly related to temperature, in this case nutrient concentration and the abundance of primary producers. Thus, at ecosystem scale, response to climate change may not follow predictions based on the temperature dependence of metabolic processes. PMID- 26258772 TI - Stable Hemiaminals: 2-Aminopyrimidine Derivatives. AB - Stable hemiaminals can be obtained in the one-pot reaction between 2 aminopyrimidine and nitrobenzaldehyde derivatives. Ten new hemiaminals have been obtained, six of them in crystal state. The molecular stability of these intermediates results from the presence of both electron-withdrawing nitro groups as substituents on the phenyl ring and pyrimidine ring, so no further stabilisation by intramolecular interaction is required. Hemiaminal molecules possess a tetrahedral carbon atom constituting a stereogenic centre. As the result of crystallisation in centrosymmetric space groups both enantiomers are present in the crystal structure. PMID- 26258773 TI - Pheonolic Compounds from the Fruits of Viburnum sargentii Koehne. AB - Seven phenolic compounds were isolated from the fruits of Viburnum sargentii Koehne by silica gel column chromatography and preparative HPLC. On the grounds of chemical and spectroscopic methods, their structures were identified as (-) Epicatechin (1), 5,7,4'-trihydroxy-flavonoid-8-C-beta-D-glucopyranoside (2), 1-(4 hydroxy-3-methoxyphenyl)-2-[4-(3-alpha-L-rhamnopyranoxypropyl)-2-methoxyphenoxy] 1,3-propane-diol (erythro) (3), 1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-alpha-L rhamnopyranoxypropyl)-2-methoxyphenoxy]-1,3-propanediol (threo) (4), (R)-4 hydroxylphenol O-(6-O-oleuropeoyl)-beta-D-glucopyranoside (5), (R)-3-methoxy-4 hydroxylphenol O-(6-O-oleuropeoyl)-beta-D-glucopyranoside (6), quercetin-3-O rutinoside (7). Compounds 5 and 6 are new monoterpene phenolic glycosides, compounds 1, 3 and 4 were isolated from the Viburnum genus for the first time, and compounds 2 and 7 from the Viburnum sargentii Koehne for the first time. Compounds 1-7 were also assayed for their antioxidant activities with DPPH free radicals. PMID- 26258774 TI - Mitochondria Retrograde Signaling and the UPR mt: Where Are We in Mammals? AB - Mitochondrial unfolded protein response is a form of retrograde signaling that contributes to ensuring the maintenance of quality control of mitochondria, allowing functional integrity of the mitochondrial proteome. When misfolded proteins or unassembled complexes accumulate beyond the folding capacity, it leads to alteration of proteostasis, damages, and organelle/cell dysfunction. Extensively studied for the ER, it was recently reported that this kind of signaling for mitochondrion would also be able to communicate with the nucleus in response to impaired proteostasis. The mitochondrial unfolded protein response (UPR(mt)) is activated in response to different types and levels of stress, especially in conditions where unfolded or misfolded mitochondrial proteins accumulate and aggregate. A specific UPR(mt) could thus be initiated to boost folding and degradation capacity in response to unfolded and aggregated protein accumulation. Although first described in mammals, the UPR(mt) was mainly studied in Caenorhabditis elegans, and accumulating evidence suggests that mechanisms triggered in response to a UPR(mt) might be different in C. elegans and mammals. In this review, we discuss and integrate recent data from the literature to address whether the UPR(mt) is relevant to mitochondrial homeostasis in mammals and to analyze the putative role of integrated stress response (ISR) activation in response to the inhibition of mtDNA expression and/or accumulation of mitochondrial mis/unfolded proteins. PMID- 26258775 TI - Potential Effects of Phytoestrogen Genistein in Modulating Acute Methotrexate Chemotherapy-Induced Osteoclastogenesis and Bone Damage in Rats. AB - Chemotherapy-induced bone damage is a frequent side effect which causes diminished bone mineral density and fracture in childhood cancer sufferers and survivors. The intensified use of anti-metabolite methotrexate (MTX) and other cytotoxic drugs has led to the need for a mechanistic understanding of chemotherapy-induced bone loss and for the development of protective treatments. Using a young rat MTX-induced bone loss model, we investigated potential bone protective effects of phytoestrogen genistein. Oral gavages of genistein (20 mg/kg) were administered daily, for seven days before, five days during, and three days after five once-daily injections (sc) of MTX (0.75 mg/kg). MTX treatment reduced body weight gain and tibial metaphyseal trabecular bone volume (p < 0.001), increased osteoclast density on the trabecular bone surface (p < 0.05), and increased the bone marrow adipocyte number in lower metaphyseal bone (p < 0.001). Genistein supplementation preserved body weight gain (p < 0.05) and inhibited ex vivo osteoclast formation of bone marrow cells from MTX-treated rats (p < 0.001). However, MTX-induced changes in bone volume, trabecular architecture, metaphyseal mRNA expression of pro-osteoclastogenic cytokines, and marrow adiposity were not significantly affected by the co-administration of genistein. This study suggests that genistein may suppress MTX-induced osteoclastogenesis; however, further studies are required to examine its potential in protecting against MTX chemotherapy-induced bone damage. PMID- 26258777 TI - Suppression of Systematic Errors of Electronic Distance Meters for Measurement of Short Distances. AB - In modern industrial geodesy, high demands are placed on the final accuracy, with expectations currently falling below 1 mm. The measurement methodology and surveying instruments used have to be adjusted to meet these stringent requirements, especially the total stations as the most often used instruments. A standard deviation of the measured distance is the accuracy parameter, commonly between 1 and 2 mm. This parameter is often discussed in conjunction with the determination of the real accuracy of measurements at very short distances (5-50 m) because it is generally known that this accuracy cannot be increased by simply repeating the measurement because a considerable part of the error is systematic. This article describes the detailed testing of electronic distance meters to determine the absolute size of their systematic errors, their stability over time, their repeatability and the real accuracy of their distance measurement. Twenty instruments (total stations) have been tested, and more than 60,000 distances in total were measured to determine the accuracy and precision parameters of the distance meters. Based on the experiments' results, calibration procedures were designed, including a special correction function for each instrument, whose usage reduces the standard deviation of the measurement of distance by at least 50%. PMID- 26258776 TI - A Perturbed MicroRNA Expression Pattern Characterizes Embryonic Neural Stem Cells Derived from a Severe Mouse Model of Spinal Muscular Atrophy (SMA). AB - Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder and the leading genetic cause of death in infants. Despite the disease-causing gene, survival motor neuron (SMN1), encodes a ubiquitous protein, SMN1 deficiency preferentially affects spinal motor neurons (MNs), leaving the basis of this selective cell damage still unexplained. As neural stem cells (NSCs) are multipotent self-renewing cells that can differentiate into neurons, they represent an in vitro model for elucidating the pathogenetic mechanism of neurodegenerative diseases such as SMA. Here we characterize for the first time neural stem cells (NSCs) derived from embryonic spinal cords of a severe SMNDelta7 SMA mouse model. SMNDelta7 NSCs behave as their wild type (WT) counterparts, when we consider neurosphere formation ability and the expression levels of specific regional and self-renewal markers. However, they show a perturbed cell cycle phase distribution and an increased proliferation rate compared to wild type cells. Moreover, SMNDelta7 NSCs are characterized by the differential expression of a limited number of miRNAs, among which miR-335-5p and miR-100-5p, reduced in SMNDelta7 NSCs compared to WT cells. We suggest that such miRNAs may be related to the proliferation differences characterizing SMNDelta7 NSCs, and may be potentially involved in the molecular mechanisms of SMA. PMID- 26258778 TI - Keeping a Good Attitude: A Quaternion-Based Orientation Filter for IMUs and MARGs. AB - Orientation estimation using low cost sensors is an important task for Micro Aerial Vehicles (MAVs) in order to obtain a good feedback for the attitude controller. The challenges come from the low accuracy and noisy data of the MicroElectroMechanical System (MEMS) technology, which is the basis of modern, miniaturized inertial sensors. In this article, we describe a novel approach to obtain an estimation of the orientation in quaternion form from the observations of gravity and magnetic field. Our approach provides a quaternion estimation as the algebraic solution of a system from inertial/magnetic observations. We separate the problems of finding the "tilt" quaternion and the heading quaternion in two sub-parts of our system. This procedure is the key for avoiding the impact of the magnetic disturbances on the roll and pitch components of the orientation when the sensor is surrounded by unwanted magnetic flux. We demonstrate the validity of our method first analytically and then empirically using simulated data. We propose a novel complementary filter for MAVs that fuses together gyroscope data with accelerometer and magnetic field readings. The correction part of the filter is based on the method described above and works for both IMU (Inertial Measurement Unit) and MARG (Magnetic, Angular Rate, and Gravity) sensors. We evaluate the effectiveness of the filter and show that it significantly outperforms other common methods, using publicly available datasets with ground-truth data recorded during a real flight experiment of a micro quadrotor helicopter. PMID- 26258779 TI - Automated Tracking of Drosophila Specimens. AB - The fruit fly Drosophila Melanogaster has become a model organism in the study of neurobiology and behavior patterns. The analysis of the way the fly moves and its behavior is of great scientific interest for research on aspects such as drug tolerance, aggression or ageing in humans. In this article, a procedure for detecting, identifying and tracking numerous specimens of Drosophila by means of computer vision-based sensing systems is presented. This procedure allows dynamic information about each specimen to be collected at each moment, and then for its behavior to be quantitatively characterized. The proposed algorithm operates in three main steps: a pre-processing step, a detection and segmentation step, and tracking shape. The pre-processing and segmentation steps allow some limits of the image acquisition system and some visual artifacts (such as shadows and reflections) to be dealt with. The improvements introduced in the tracking step allow the problems corresponding to identity loss and swaps, caused by the interaction between individual flies, to be solved efficiently. Thus, a robust method that compares favorably to other existing methods is obtained. PMID- 26258780 TI - The Marine-Derived Fungus Clonostachys rosea, Source of a Rare Conjugated 4-Me 6E,8E-hexadecadienoic Acid Reducing Viability of MCF-7 Breast Cancer Cells and Gene Expression of Lipogenic Enzymes. AB - A marine-derived strain of Clonostachys rosea isolated from sediments of the river Loire estuary (France) was investigated for its high lipid production. The fungal strain was grown on six different culture media to explore lipid production changes. An original branched conjugated fatty acid, mainly present in triglycerides and mostly produced when grown on DCA (23% of total fatty acid composition). It was identified as 4-Me-6E,8E-hexadecadienoic on the basis of spectroscopic analyses. This fatty acid reduced viability of MCF-7 breast cancer cells in a dose dependent manner (up to 63%) at physiological free fatty acid human plasma concentration (100 MUM). Reduction of gene expression of two lipogenic enzymes, the acetyl CoA carboxylase (ACC) and the fatty acid synthase (FAS) was evaluated to explore the mechanisms of action of 4-Me-6E,8E-16:2 acid. At 50 MUM, 50% and 35% of mRNA gene expression inhibition were observed for ACC and FAS, respectively. PMID- 26258781 TI - Epipolythiodiketopiperazines from the Marine Derived Fungus Dichotomomyces cejpii with NF-kappaB Inhibitory Potential. AB - The Ascomycota Dichotomomyces cejpii was isolated from the marine sponge Callyspongia cf. C. flammea. A new gliotoxin derivative, 6 acetylmonodethiogliotoxin (1) was obtained from fungal extracts. Compounds 2 and 3, methylthio-gliotoxin derivatives were formerly only known as semi-synthetic compounds and are here described as natural products. Additionally the polyketide heveadride (4) was isolated. Compounds 1, 2 and 4 dose-dependently down-regulated TNFalpha-induced NF-kappaB activity in human chronic myeloid leukemia cells with IC50s of 38.5 +/- 1.2 uM, 65.7 +/- 2.0 uM and 82.7 +/- 11.3 uM, respectively. The molecular mechanism was studied with the most potent compound 1 and results indicate downstream inhibitory effects targeting binding of NF-kappaB to DNA. Compound 1 thus demonstrates potential of epimonothiodiketopiperazine-derived compounds for the development of NF-kappaB inhibitors. PMID- 26258782 TI - Brand Cigarillos: Low Price but High Particulate Matter Levels-Is Their Favorable Taxation in the European Union Justified? AB - BACKGROUND: Second hand smoke (ETS)-associated particulate matter (PM) contributes considerably to indoor air contamination and constitutes a health risk for passive smokers. Easy to measure, PM is a useful parameter to estimate the dosage of ETS that passive smokers are exposed to. Apart from its suitability as a surrogate parameter for ETS-exposure, PM itself affects human morbidity and mortality in a dose-dependent manner. We think that ETS-associated PM should be considered an independent hazard factor, separately from the many other known harmful compounds of ETS. We believe that brand-specific and tobacco-product specific differences in the release of PM matter and that these differences are of public interest. METHODS: To generate ETS of cigarettes and cigarillos as standardized and reproducible as possible, an automatic second hand smoke emitter (AETSE) was developed and placed in a glass chamber. L&M cigarettes ("without additives", "red label", "blue label"), L&M filtered cigarillos ("red") and 3R4F standard research cigarettes (as reference) were smoked automatically according to a self-developed, standardized protocol until the tobacco product was smoked down to 8 mm distance from the tipping paper of the filter. RESULTS: Mean concentration (Cmean) and area under the curve (AUC) in a plot of PM2.5 against time were measured, and compared. CmeanPM2.5 were found to be 518 MUg/m(3) for 3R4F cigarettes, 576 MUg/m(3) for L&M "without additives" ("red"), 448 MUg/m(3) for L&M "blue label", 547 MUg/m(3) for L&M "red label", and 755 MUg/m(3) for L&M filtered cigarillos ("red"). AUCPM2.5-values were 208,214 MUg/m(3).s for 3R4F reference cigarettes, 204,629 MUg/m(3).s for L&M "without additives" ("red"), 152,718 MUg/m(3).s for L&M "blue label", 238,098 MUg/m(3).s for L&M "red label" and 796,909 MUg/m(3).s for L&M filtered cigarillos ("red"). CONCLUSION: Considering the large and significant differences in particulate matter emissions between cigarettes and cigarillos, we think that a favorable taxation of cigarillos is not justifiable. PMID- 26258783 TI - Association between the Hygiene Index Values of Live Fresh Aquatic Products and Food-Borne Diarrhea in the Population of the Ningbo Area in China. AB - To investigate the association of the hygiene index values of live fresh aquatic products and food-borne diarrhea in the population of the Ningbo area in China. Volatile basic nitrogen (VBN), histamine (HIS), indole, tetrodotoxin (TTX), and paralytic, neurotoxic, amnesic and diarrhetic shellfish poisons (PSP, NSP, ASP, and DSP, respectively) in the samples of live fresh aquatic products and food borne diarrhea cases in six studied districts were analyzed. Results indicate that the incidence rate of food-borne diarrhea is related to the hygiene index values. Aside from VBN, the main risk factors related to food-borne diarrhea in edible aquatic products include DSP (in marine fish, shrimp, and other shellfishes), NSP, and ASP (in marine shrimp and crab). Hygiene index values among different species were significantly different. No significant difference in the monitoring index values was found among the six different studied districts. The reported cases of food-borne diarrhea were positively associated with VBN and DSP in aquatic products in Haishu, Jiangbei, Zhenhai, and Beilun, as well as VBN and NSP in aquatic products in Jiangdong and Yinzhou. In conclusion, VBN, DSP, NSP, and ASP are important risk factors for the occurring of food-borne diarrhea in the population of the Ningbo area in China. PMID- 26258784 TI - The Relationship of Policymaking and Networking Characteristics among Leaders of Large Urban Health Departments. AB - BACKGROUND: The relationship between policy networks and policy development among local health departments (LHDs) is a growing area of interest to public health practitioners and researchers alike. In this study, we examine policy activity and ties between public health leadership across large urban health departments. METHODS: This study uses data from a national profile of local health departments as well as responses from a survey sent to three staff members (local health official, chief of policy, chief science officer) in each of 16 urban health departments in the United States. Network questions related to frequency of contact with health department personnel in other cities. Using exponential random graph models, network density and centrality were examined, as were patterns of communication among those working on several policy areas using exponential random graph models. RESULTS: All 16 LHDs were active in communicating about chronic disease as well as about use of alcohol, tobacco, and other drugs (ATOD). Connectedness was highest among local health officials (density = .55), and slightly lower for chief science officers (d = .33) and chiefs of policy (d = .29). After accounting for organizational characteristics, policy homophily (i.e., when two network members match on a single characteristic) and tenure were the most significant predictors of formation of network ties. CONCLUSION: Networking across health departments has the potential for accelerating the adoption of public health policies. This study suggests similar policy interests and formation of connections among senior leadership can potentially drive greater connectedness among other staff. PMID- 26258785 TI - Analysis on Two Typical Landslide Hazard Phenomena in The Wenchuan Earthquake by Field Investigations and Shaking Table Tests. AB - Based on our field investigations of landslide hazards in the Wenchuan earthquake, some findings can be reported: (1) the multi-aspect terrain facing empty isolated mountains and thin ridges reacted intensely to the earthquake and was seriously damaged; (2) the slope angles of most landslides was larger than 45 degrees . Considering the above disaster phenomena, the reasons are analyzed based on shaking table tests of one-sided, two-sided and four-sided slopes. The analysis results show that: (1) the amplifications of the peak accelerations of four-sided slopes is stronger than that of the two-sided slopes, while that of the one-sided slope is the weakest, which can indirectly explain the phenomena that the damage is most serious; (2) the amplifications of the peak accelerations gradually increase as the slope angles increase, and there are two inflection points which are the point where the slope angle is 45 degrees and where the slope angle is 50 degrees , respectively, which can explain the seismic phenomenon whereby landslide hazards mainly occur on the slopes whose slope angle is bigger than 45 degrees . The amplification along the slope strike direction is basically consistent, and the step is smooth. PMID- 26258786 TI - Characterization of the HCMV-Specific CD4 T Cell Responses that Are Associated with Protective Immunity. AB - Most humans become infected with human cytomegalovirus (HCMV). Typically, the immune system controls the infection, but the virus persists and can reactivate in states of immunodeficiency. While substantial information is available on the contribution of CD8 T cells and antibodies to anti-HCMV immunity, studies of the TH1, TH2, and TH17 subsets have been limited by the low frequency of HCMV specific CD4 T cells in peripheral blood mononuclear cell (PBMC). Using the enzyme-linked Immunospotr assay (ELISPOT) that excels in low frequency measurements, we have established these in a sizable cohort of healthy HCMV controllers. Cytokine recall responses were seen in all seropositive donors. Specifically, interferon (IFN)- and/or interleukin (IL)-17 were seen in isolation or with IL-4 in all test subjects. IL-4 recall did not occur in isolation. While the ratios of TH1, TH2, and TH17 cells exhibited substantial variations between different individuals these ratios and the frequencies were relatively stable when tested in samples drawn up to five years apart. IFN- and IL-2 co-expressing polyfunctional cells were seen in most subjects. Around half of the HCMV-specific CD4 cells were in a reversible state of exhaustion. The data provided here established the TH1, TH2, and TH17 characteristic of the CD4 cells that convey immune protection for successful immune surveillance against which reactivity can be compared when the immune surveillance of HCMV fails. PMID- 26258787 TI - RNA-Dependent RNA Polymerases of Picornaviruses: From the Structure to Regulatory Mechanisms. AB - RNA viruses typically encode their own RNA-dependent RNA polymerase (RdRP) to ensure genome replication within the infected cells. RdRP function is critical not only for the virus life cycle but also for its adaptive potential. The combination of low fidelity of replication and the absence of proofreading and excision activities within the RdRPs result in high mutation frequencies that allow these viruses a rapid adaptation to changing environments. In this review, we summarize the current knowledge about structural and functional aspects on RdRP catalytic complexes, focused mainly in the Picornaviridae family. The structural data currently available from these viruses provided high-resolution snapshots for a range of conformational states associated to RNA template-primer binding, rNTP recognition, catalysis and chain translocation. As these enzymes are major targets for the development of antiviral compounds, such structural information is essential for the design of new therapies. PMID- 26258788 TI - Structural and Functional Properties of the Hepatitis C Virus p7 Viroporin. AB - The high prevalence of hepatitis C virus (HCV) infection in the human population has triggered intensive research efforts that have led to the development of curative antiviral therapy. Moreover, HCV has become a role model to study fundamental principles that govern the replication cycle of a positive strand RNA virus. In fact, for most HCV proteins high-resolution X-ray and NMR (Nuclear Magnetic Resonance)-based structures have been established and profound insights into their biochemical and biological properties have been gained. One example is p7, a small hydrophobic protein that is dispensable for RNA replication, but crucial for the production and release of infectious HCV particles from infected cells. Owing to its ability to insert into membranes and assemble into homo oligomeric complexes that function as minimalistic ion channels, HCV p7 is a member of the viroporin family. This review compiles the most recent findings related to the structure and dual pore/ion channel activity of p7 of different HCV genotypes. The alternative conformations and topologies proposed for HCV p7 in its monomeric and oligomeric state are described and discussed in detail. We also summarize the different roles p7 might play in the HCV replication cycle and highlight both the ion channel/pore-like function and the additional roles of p7 unrelated to its channel activity. Finally, we discuss possibilities to utilize viroporin inhibitors for antagonizing p7 ion channel/pore-like activity. PMID- 26258790 TI - Correlates of University Students' Soft and Energy Drink Consumption According to Gender and Residency. AB - This study assessed personal and environmental correlates of Belgian university students' soft and energy drink consumption and investigated whether these associations were moderated by gender or residency. Four hundred twenty-five university students completed a self-reported on-line questionnaire assessing socio-demographics, health status, soft and energy drink consumption, as well as personal and environmental factors related to soft and energy drink consumption. Multiple linear regression analyses were conducted. Students believing soft drink intake should be minimized (individual subjective norm), finding it less difficult to avoid soft drinks (perceived behavioral control), being convinced they could avoid soft drinks in different situations (self-efficacy), having family and friends who rarely consume soft drinks (modelling), and having stricter family rules about soft drink intake were less likely to consume soft drinks. Students showing stronger behavioral control, having stricter family rules about energy drink intake, and reporting lower energy drink availability were less likely to consume energy drinks. Gender and residency moderated several associations between psychosocial constructs and consumption. Future research should investigate whether interventions focusing on the above personal and environmental correlates can indeed improve university students' beverage choices. PMID- 26258791 TI - OTA-Grapes: A Mechanistic Model to Predict Ochratoxin A Risk in Grapes, a Step beyond the Systems Approach. AB - Ochratoxin A (OTA) is a fungal metabolite dangerous for human and animal health due to its nephrotoxic, immunotoxic, mutagenic, teratogenic and carcinogenic effects, classified by the International Agency for Research on Cancer in group 2B, possible human carcinogen. This toxin has been stated as a wine contaminant since 1996. The aim of this study was to develop a conceptual model for the dynamic simulation of the A. carbonarius life cycle in grapes along the growing season, including OTA production in berries. Functions describing the role of weather parameters in each step of the infection cycle were developed and organized in a prototype model called OTA-grapes. Modelling the influence of temperature on OTA production, it emerged that fungal strains can be shared in two different clusters, based on the dynamic of OTA production and according to the optimal temperature. Therefore, two functions were developed, and based on statistical data analysis, it was assumed that the two types of strains contribute equally to the population. Model validation was not possible because of poor OTA contamination data, but relevant differences in OTA-I, the output index of the model, were noticed between low and high risk areas. To our knowledge, this is the first attempt to assess/model A. carbonarius in order to predict the risk of OTA contamination in grapes. PMID- 26258789 TI - Dietary Selenium Levels Affect Selenoprotein Expression and Support the Interferon-gamma and IL-6 Immune Response Pathways in Mice. AB - Selenium is an essential element that is required to support a number of cellular functions and biochemical pathways. The objective of this study was to examine the effects of reduced dietary selenium levels on gene expression to assess changes in expression of non-selenoprotein genes that may contribute to the physiological consequences of selenium deficiency. Mice were fed diets that were either deficient in selenium or supplemented with selenium in the form of sodium selenite for six weeks. Differences in liver mRNA expression and translation were measured using a combination of ribosome profiling, RNA-Seq, microarrays, and qPCR. Expression levels and translation of mRNAs encoding stress-related selenoproteins were shown to be up-regulated by increased selenium status, as were genes involved in inflammation and response to interferon-gamma. Changes in serum cytokine levels were measured which confirmed that interferon-gamma, as well as IL-6, were increased in selenium adequate mice. Finally, microarray and qPCR analysis of lung tissue demonstrated that the selenium effects on immune function are not limited to liver. These data are consistent with previous reports indicating that adequate selenium levels can support beneficial immune responses, and further identify the IL-6 and interferon-gamma pathways as being responsive to dietary selenium intake. PMID- 26258792 TI - Citreoviridin Induces Autophagy-Dependent Apoptosis through Lysosomal Mitochondrial Axis in Human Liver HepG2 Cells. AB - Citreoviridin (CIT) is a mycotoxin derived from fungal species in moldy cereals. In our previous study, we reported that CIT stimulated autophagosome formation in human liver HepG2 cells. Here, we aimed to explore the relationship of autophagy with lysosomal membrane permeabilization and apoptosis in CIT-treated cells. Our data showed that CIT increased the expression of LC3-II, an autophagosome biomarker, from the early stage of treatment (6 h). After treatment with CIT for 12 h, lysosomal membrane permeabilization occurred, followed by the release of cathepsin D in HepG2 cells. Inhibition of autophagosome formation with siRNA against Atg5 attenuated CIT-induced lysosomal membrane permeabilization. In addition, CIT induced collapse of mitochondrial transmembrane potential as assessed by JC-1 staining. Furthermore, caspase-3 activity assay showed that CIT induced apoptosis in HepG2 cells. Inhibition of autophagosome formation attenuated CIT-induced apoptosis, indicating that CIT-induced apoptosis was autophagy-dependent. Cathepsin D inhibitor, pepstatin A, relieved CIT-induced apoptosis as well, suggesting the involvement of the lysosomal-mitochondrial axis in CIT-induced apoptosis. Taken together, our data demonstrated that CIT induced autophagy-dependent apoptosis through the lysosomal-mitochondrial axis in HepG2 cells. The study thus provides essential mechanistic insight, and suggests clues for the effective management and treatment of CIT-related diseases. PMID- 26258793 TI - Not so Fast: Co-Requirements for Sonic Hedgehog Induced Brain Tumorigenesis. AB - The Sonic hedgehog (Shh) pathway plays an integral role in cellular proliferation during normal brain development and also drives growth in a variety of cancers including brain cancer. Clinical trials of Shh pathway inhibitors for brain tumors have yielded disappointing results, indicating a more nuanced role for Shh signaling. We postulate that Shh signaling does not work alone but requires co activation of other signaling pathways for tumorigenesis and stem cell maintenance. This review will focus on the interplay between the Shh pathway and these pathways to promote tumor growth in brain tumors, presenting opportunities for the study of combinatorial therapies. PMID- 26258794 TI - Breast Cancer Survivorship Care: Targeting a Colorectal Cancer Education Intervention. AB - Breast cancer survivors are at risk of developing a second primary cancer. Colorectal cancer (CRC) is one of the leading second primary cancers, and it is often preventable. We developed a multi-component educational tool to inform and encourage women breast cancer survivors to engage in CRC screening. To assess the strengths and weakness of the tool and to improve the relevancy to the target audience, we convened four focus groups of women breast cancer survivors in Missouri. We also assessed the potential impact of the tool on the knowledge, attitudes, and beliefs regarding CRC and collected information on the barriers to CRC screening through pre- and post-focus groups' questionnaires. A total of 43 women breast cancer survivors participated and provided very valuable suggestions on design and content to update the tool. Through the process and comparing pre- and post-focus group assessments, a significantly higher proportion of breast cancer survivors strongly agreed or agreed that CRC is preventable (78.6% vs. 96.9%, p = 0.02) and became aware that they were at a slightly increased risk for CRC (18.6% vs. 51.7%, p = 0.003). The most cited barrier was the complexity of preparation for colonoscopy. PMID- 26258795 TI - Role of MicroRNAs-221/222 in Digestive Systems. AB - MiR-221 and miR-222 (miR-221/222) are well-studied oncogenic microRNAs that are frequently upregulated in several types of human tumors, such as esophageal adenocarcinoma, gastric adenocarcinoma, colorectal adenocarcinoma, hepatocellular carcinoma, and pancreatic ductal adenocarcinoma. In these cancers, silencing miR 221/222 could represent a novel anti-tumor approach to inhibit tumor growth and metastasis. On the other hand, miR-221/222 also play onco-suppressive roles in cholangiocarcinoma and gastrointestinal stromal tumors (GISTs). Here we will review the roles of miR-221/222 in digestive systems and their possibility as prognostic and therapeutic tools. PMID- 26258796 TI - Peptide Amphiphiles in Corneal Tissue Engineering. AB - The increasing interest in effort towards creating alternative therapies have led to exciting breakthroughs in the attempt to bio-fabricate and engineer live tissues. This has been particularly evident in the development of new approaches applied to reconstruct corneal tissue. The need for tissue-engineered corneas is largely a response to the shortage of donor tissue and the lack of suitable alternative biological scaffolds preventing the treatment of millions of blind people worldwide. This review is focused on recent developments in corneal tissue engineering, specifically on the use of self-assembling peptide amphiphiles for this purpose. Recently, peptide amphiphiles have generated great interest as therapeutic molecules, both in vitro and in vivo. Here we introduce this rapidly developing field, and examine innovative applications of peptide amphiphiles to create natural bio-prosthetic corneal tissue in vitro. The advantages of peptide amphiphiles over other biomaterials, namely their wide range of functions and applications, versatility, and transferability are also discussed to better understand how these fascinating molecules can help solve current challenges in corneal regeneration. PMID- 26258798 TI - Suspect Height Estimation Using the Faro Focus(3D) Laser Scanner. AB - At present, very little research has been devoted to investigating the ability of laser scanning technology to accurately measure height from surveillance video. The goal of this study was to test the accuracy of one particular laser scanner to estimate suspect height from video footage. The known heights of 10 individuals were measured using an anthropometer. The individuals were then recorded on video walking along a predetermined path in a simulated crime scene environment both with and without headwear. The difference between the known heights and the estimated heights obtained from the laser scanner software were compared using a one-way t-test. The height estimates obtained from the software were not significantly different from the known heights whether individuals were wearing headwear (p = 0.186) or not (p = 0.707). Thus, laser scanning is one technique that could potentially be used by investigators to determine suspect height from video footage. PMID- 26258799 TI - Identification of novel peptides for horse meat speciation in highly processed foodstuffs. AB - There is a need for robust analytical methods to support enforcement of food labelling legislation. Proteomics is emerging as a complementary methodology to existing tools such as DNA and antibody-based techniques. Here we describe the development of a proteomics strategy for the determination of meat species in highly processed foods. A database of specific peptides for nine relevant animal species was used to enable semi-targeted species determination. This principle was tested for horse meat speciation, and a range of horse-specific peptides were identified as heat stable marker peptides for the detection of low levels of horse meat in mixtures with other species. PMID- 26258800 TI - Evolving the Palliative Care Workforce to Provide Responsive, Serious Illness Care. PMID- 26258797 TI - Frailty Phenotypes, Disability, and Outcomes in Adult Candidates for Lung Transplantation. AB - RATIONALE: Frailty is associated with morbidity and mortality in abdominal organ transplantation but has not been examined in lung transplantation. OBJECTIVES: To examine the construct and predictive validity of frailty phenotypes in lung transplant candidates. METHODS: In a multicenter prospective cohort, we measured frailty with the Fried Frailty Phenotype (FFP) and Short Physical Performance Battery (SPPB). We evaluated construct validity through comparisons with conceptually related factors. In a nested case-control study of frail and nonfrail subjects, we measured serum IL-6, tumor necrosis factor receptor 1, insulin-like growth factor I, and leptin. We estimated the association between frailty and disability using the Lung Transplant Valued Life Activities disability scale. We estimated the association between frailty and risk of delisting or death before transplant using multivariate logistic and Cox models, respectively. MEASUREMENTS AND MAIN RESULTS: Of 395 subjects, 354 completed FFP assessments and 262 completed SPPB assessments; 28% were frail by FFP (95% confidence interval [CI], 24-33%) and 10% based on the SPPB (95% CI, 7-14%). By either measure, frailty correlated more strongly with exercise capacity and grip strength than with lung function. Frail subjects tended to have higher plasma IL 6 and tumor necrosis factor receptor 1 and lower insulin-like growth factor I and leptin. Frailty by either measure was associated with greater disability. After adjusting for age, sex, diagnosis, and transplant center, both FFP and SPPB were associated with increased risk of delisting or death before lung transplant. For every 1-point worsening in score, hazard ratios were 1.30 (95% CI, 1.01-1.67) for FFP and 1.53 (95% CI, 1.19-1.59) for SPPB. CONCLUSIONS: Frailty is prevalent among lung transplant candidates and is independently associated with greater disability and an increased risk of delisting or death. PMID- 26258801 TI - Characterization and evaluation of metformin-loaded solid lipid nanoparticles for celluar and mitochondrial uptake. AB - Considered a popular drug for diabetes in recent years, metformin was determined to have a moderate anti-tumor effect, particularly in breast cancer. In this study, the anticancer mechanism of metformin was verified by preparing solid lipid nanoparticles (SLNs) and chitosan-modified solid lipid nanoparticles (CSLNs) containing metformin and then estimating the potential of these SLNs for uptake in cells and mitochondria. Metformin-SLNs were prepared using an emulsification and low-temperature solidification method. The mean particle size, zeta potential, entrapment efficiency, and loading efficiency of metformin-SLNs and metformin chitosan-modified SLNs were 102.3 +/- 4.16 and 200.1 +/- 17.69 nm, 21.25 +/- 4.89 and 50.6 +/- 4.09 mv, 26.25 +/- 2.59% and 33.6 +/- 2.21%, and 1.74 +/- 0.16% and 1.46 +/- 0.10%, respectively. TEM images showed that both the nanoparticles had spherical morphologies with no aggregation. Results of cellular and mitochondrial uptake showed that the metformin-SLNs were easier to uptake in cells and mitochondria than the pure drug group (that was the control group without SLN structure modification). The findings of this research provide a basis for conducting further studies on the anticancer mechanism of metformin. PMID- 26258802 TI - P-glycoprotein inhibitors: synthesis and in vitro evaluation of a preactivated thiomer. AB - The aim of this study was to synthesize the preactivated thiomer poly(acrylic acid)-cyteine-2-mercaptonicotinic acid (PAA-Cys-2MNA) and to evaluate its P glycoprotein (P-gp) inhibitory properties. The thiomer (PAA-Cys) was synthesized by covalent immobilization of thiol groups on poly(acrylic acid) (PAA) with a molecular mass of 250 kDa followed by immobilization of 2-mercaptonicotinic acid (2MNA) to thiol groups via disulfide bond formation resulting in PAA-Cys-2MNA. P gp inhibitory effect of this preactivated thiomer was evaluated on Caco-2 cells. Transports of rhodamine 123 at 37 degrees C with and without verapamil and at 4 degrees C were performed to evaluate P-gp function of cells. In total, 1571.81 +/ 156.18 umol thiol groups were immobilized per gram of polymer that were in the next step by 99.88% preactivated. The enhancement ratios of Papp calculated from the ratio between Papp of rhodamine 123 in the presence of P-gp inhibitors and Papp of rhodamine 123 alone were 2.36, 2.09, and 1.84-fold in the presence of PAA Cys-2MNA, PAA-Cys, and PAA, respectively. Because of its pronounced P-gp inhibitory effect, PAA-Cys-2MNA could be considered as promising macromolecular P gp inhibitor for various drug delivery systems. PMID- 26258803 TI - Estimation of Coast-Wide Population Trends of Marbled Murrelets in Canada Using a Bayesian Hierarchical Model. AB - Species at risk with secretive breeding behaviours, low densities, and wide geographic range pose a significant challenge to conservation actions because population trends are difficult to detect. Such is the case with the Marbled Murrelet (Brachyramphus marmoratus), a seabird listed as 'Threatened' by the Species at Risk Act in Canada largely due to the loss of its old growth forest nesting habitat. We report the first estimates of population trend of Marbled Murrelets in Canada derived from a monitoring program that uses marine radar to detect birds as they enter forest watersheds during 923 dawn surveys at 58 radar monitoring stations within the six Marbled Murrelet Conservation Regions on coastal British Columbia, Canada, 1996-2013. Temporal trends in radar counts were analyzed with a hierarchical Bayesian multivariate modeling approach that controlled for variation in tilt of the radar unit and day of year, included year specific deviations from the overall trend ('year effects'), and allowed for trends to be estimated at three spatial scales. A negative overall trend of 1.6%/yr (95% credibility interval: -3.2%, 0.01%) indicated moderate evidence for a coast-wide decline, although trends varied strongly among the six conservation regions. Negative annual trends were detected in East Vancouver Island (-9%/yr) and South Mainland Coast (-3%/yr) Conservation Regions. Over a quarter of the year effects were significantly different from zero, and the estimated standard deviation in common-shared year effects between sites within each region was about 50% per year. This large common-shared interannual variation in counts may have been caused by regional movements of birds related to changes in marine conditions that affect the availability of prey. PMID- 26258804 TI - Cost-effectiveness of physical activity among women with menopause symptoms: findings from a randomised controlled trial. AB - Menopause is a period that may predispose one to a decrease in muscle strength, cardiorespiratory fitness, and quality of life. A study was carried out to evaluate the cost-effectiveness of physical activity among women displaying symptoms of menopause. The cost-effectiveness analysis was based on data from a six-month randomised controlled trial (n = 151). The women in the intervention group engaged in an unsupervised session of at least 50 minutes of physical activity four times a week. The control group continued their physical activity as before. An incremental cost-effectiveness ratio (ICER) was calculated in terms of maximal oxygen consumption, lean muscle mass, and quality-adjusted life years (QALYs) gained. A bootstrap technique was utilised to estimate uncertainty around the point estimate for ICER associated with the intervention. The mean total cost in the intervention group was ?1,307 (SEM: ?311) and in the control group was ?1,253 (SEM: ?279, p = 0.10) per person. The mean intervention cost was ?208 per person. After six months of the behaviour-change intervention, the ICER was ?63 for a 1 ml/kg/min improvement in cardiorespiratory fitness, the additional cost per one-gram increase in lean muscle mass was ?126, and the cost per QALY gained was ?46. According to the findings, physical activity among menopausal women was cost-effective for cardiorespiratory fitness, for lean muscle mass, and for QALYs gained, since the intervention was more effective than the actions within the control group and the additional effects of physical activity were gained at a very low price. From the societal perspective, the intervention used may promote ability to work and thereby save on further costs associated with early retirement or disability pension if the physical-activity level remains at least the same as during the intervention. PMID- 26258805 TI - MicroRNA regulation of viral immunity, latency, and carcinogenesis of selected tumor viruses and HIV. AB - MicroRNAs (miRNAs) function as key regulators in immune responses and cancer development. In the contexts of infection with oncogenic viruses, miRNAs are engaged in viral persistence, latency establishment and maintenance, and oncogenesis. In this review, we summarize the potential roles and mechanisms of viral and cellular miRNAs in the host-pathogen interactions during infection with selected tumor viruses and HIV, which include (i) repressing viral replication and facilitating latency establishment by targeting viral transcripts, (ii) evading innate and adaptive immune responses via toll-like receptors, RIG-I-like receptors, T-cell receptor, and B-cell receptor pathways by targeting signaling molecules such as TRAF6, IRAK1, IKKepsilon, and MyD88, as well as downstream targets including regulatory cytokines such as tumor necrosis factor alpha, interferon gamma, interleukin 10, and transforming growth factor beta, (iii) antagonizing intrinsic and extrinsic apoptosis pathways by targeting pro apoptotic or anti-apoptotic gene transcripts such as the Bcl-2 family and caspase 3, (iv) modulating cell proliferation and survival through regulation of the Wnt, PI3K/Akt, Erk/MAPK, and Jak/STAT signaling pathways, as well as the signaling pathways triggered by viral oncoproteins such as Epstein-Barr Virus LMP1, by targeting Wnt-inhibiting factor 1, SHIP, pTEN, and SOCSs, and (v) regulating cell cycle progression by targeting cell cycle inhibitors such as p21/WAF1 and p27/KIP1. Further elucidation of the interaction between miRNAs and these key biological events will facilitate our understanding of the pathogenesis of viral latency and oncogenesis and may lead to the identification of miRNAs as novel targets for developing new therapeutic or preventive interventions. PMID- 26258807 TI - Dual Gold Catalysis: Stepwise Catalyst Transfer via Dinuclear Clusters. AB - The interest in and use of dual gold catalysts is forever increasing, but little is known of the mechanism for the catalyst transfer and its effect on the continued high turnover frequency. Herein, we present a computational investigation of the mechanism for the final intermolecular catalyst transfer in the synthesis of dibenzopentalene from 1-ethynyl-2-(phenylethynyl)benzene. Three different scenarios have been explored: a single catalyst transfer from the monoaurated product complex, the analogous water mediated single transfer, and a dual catalyst transfer from the diaurated product complex. Transition structures have been found for each step of the three possible pathways, and a stepwise dual catalyst transfer has proven to be the lowest energy pathway. We here describe a three-step transfer of two gold moieties from one dibenzopentalene to one diyne. This process directly gives the sigma,pi-gold coordinated diyne for the further intramolecular cyclization reaction. PMID- 26258806 TI - Initiated Chemical Vapor Deposition (iCVD) of Highly Cross-Linked Polymer Films for Advanced Lithium-Ion Battery Separators. AB - We report an initiated chemical vapor deposition (iCVD) process to coat polyethylene (PE) separators in Li-ion batteries with a highly cross-linked, mechanically strong polymer, namely, polyhexavinyldisiloxane (pHVDS). The highly cross-linked but ultrathin pHVDS films can only be obtained by a vapor-phase process, because the pHVDS is insoluble in most solvents and thus infeasible with conventional solution-based methods. Moreover, even after the pHVDS coating, the initial porous structure of the separator is well preserved owing to the conformal vapor-phase deposition. The coating thickness is delicately controlled by deposition time to the level that the pore size decreases to below 7% compared to the original dimension. The pHVDS-coated PE shows substantially improved thermal stability and electrolyte wettability. After incubation at 140 degrees C for 30 min, the pHVDS-coated PE causes only a 12% areal shrinkage (versus 90% of the pristine separator). The superior wettability results in increased electrolyte uptake and ionic conductivity, leading to significantly improved rate performance. The current approach is applicable to a wide range of porous polymeric separators that suffer from thermal shrinkage and poor electrolyte wetting. PMID- 26258808 TI - Association between breastfeeding and risk of endometrial cancer: a meta-analysis of epidemiological studies. AB - Epidemiological studies have yielded inconsistent findings on the relationship between breastfeeding and the risk of endometrial cancer. Pertinent studies were identified by searching PubMed, Embase, and Web of Knowledge through February 2015 and by reviewing the reference lists of retrieved articles. Study-specific estimates were pooled using a random-effects model. Dose-response analysis was carried out for every 6-month increase in the duration of breastfeeding in relation to the risk of endometrial cancer. Three prospective and 11 case-control studies were included in this meta-analysis. The pooled estimates for ever compared with never breastfeeding and the longest duration of breastfeeding compared with the shortest were 0.91 [95% confidence interval (CI): 0.75-1.09] and 0.76 (95% CI: 0.59-0.98). The risk of endometrial cancer decreased by 7% for every 6-month increase in the duration of breastfeeding (relative risk: 0.93; 95% CI: 0.88-0.97). This study provides evidence that ever breastfeeding, particularly a longer duration of breastfeeding, is associated with a lower risk of endometrial cancer. PMID- 26258809 TI - The variation trends of SFRP2 methylation of tissue, feces, and blood detection in colorectal cancer development. AB - The susceptibility of secreted frizzled-related protein 2 (SFRP2) methylation in colorectal cancer (CRC) has been studied previously. The aim of this study was to determine the risk sizes and variation trends of SFRP2 methylation in CRC development in Chinese populations. Subgroup meta-analysis and the least-squares curve-fitting method were carried out to analyze the risk of SFRP2 methylation in tissue, feces, and blood detection from 2221 samples, including a total of 1103 cases of CRC, 459 cases of adenoma, 257 cases of polyps, and 402 controls. The data showed that odds ratios (95% confidence intervals) between CRC and controls for tissue, feces, and blood detection were 334.01 (104.42-1068.39), 63.76 (20.62 197.63), and 133.75 (18.32-976.32), respectively. There were also significant differences between tissue and feces or blood as well as between feces and blood methylation frequency. These results showed that the risk size in tissue was much greater than that in feces and that in blood. The results pointed out that three curves in tissue, feces, and blood detection described the variation trends of methylation incidence from the control to polyp, to adenoma and to CRC, and that the variation trend of the risk size of SFRP2 methylation was synchronized with the histological evolution process of CRC. The variation trend of the risk size of SFRP2 methylation incidence is consistent with the histological evolution process of CRC. The susceptibility to SFRP2 methylation is an important biomarker in the study of early diagnosis of CRC and high-risk patients. PMID- 26258810 TI - Pentoxifylline prevents nonalcoholic steatohepatitis-related liver pre-neoplasms by inhibiting hepatic inflammation and lipogenesis. AB - Nonalcoholic steatohepatitis (NASH) has gained attention as a hepatic manifestation associated with metabolic syndrome and one of the causes for chronic liver damage leading to hepatocellular carcinoma. Although no standard medicinal treatment for NASH has been established, pentoxifylline (PTX), a medicine used to improve circulation, has recently been reported to ameliorate the histopathological appearance of NASH. In the present study, we investigated the effects of PTX on the development of NASH and diethylnitrosamine-induced liver tumorigenesis in C57BLKS/J- +Lepr/+Lepr obese and diabetic mice, which are considered a rodent model for NASH-related hepatocarcinogenesis. Mice were administered diethylnitrosamine, and then they received water with or without PTX. At the time of sacrifice, the development of hepatic pre-neoplastic lesions was significantly suppressed in the PTX groups. Hepatic triglyceride contents were decreased by PTX administration. The serum levels of triglyceride, free fatty acid, and alanine aminotransferase were all decreased by PTX treatment, as was the mRNA expression of proinflammatory cytokines, macrophage-inducing chemokines, and several lipogenic genes in the liver. In-vitro studies also showed that PTX treatment decreased the expression of several lipogenic genes and chemokines in cell lines. These findings suggest that PTX prevents NASH-related liver tumorigenesis by attenuating chronic hepatic inflammation and decreasing lipogenic gene expression in the liver. PMID- 26258811 TI - Ingenol mebutate: an unconventional treatment proposal. PMID- 26258812 TI - Detecting and Number Counting of Single Engineered Nanoparticles by Digital Particle Polymerase Chain Reaction. AB - The concentrations of nanoparticles present in colloidal dispersions are usually measured and given in mass concentration (e.g. mg/mL), and number concentrations can only be obtained by making assumptions about nanoparticle size and morphology. Additionally traditional nanoparticle concentration measures are not very sensitive, and only the presence/absence of millions/billions of particles occurring together can be obtained. Here, we describe a method, which not only intrinsically results in number concentrations, but is also sensitive enough to count individual nanoparticles, one by one. To make this possible, the sensitivity of the polymerase chain reaction (PCR) was combined with a binary (=0/1, yes/no) measurement arrangement, binomial statistics and DNA comprising monodisperse silica nanoparticles. With this method, individual tagged particles in the range of 60-250 nm could be detected and counted in drinking water in absolute number, utilizing a standard qPCR device within 1.5 h of measurement time. For comparison, the method was validated with single particle inductively coupled plasma mass spectrometry (sp-ICPMS). PMID- 26258813 TI - Health after pregnancy in the mother with diabetes. AB - Progression of retinopathy and nephropathy in women with diabetes occurs, at least temporarily, during pregnancy and postpartum. However, normotensive pregnancy seems to have no detrimental effects regarding the long-term progression of any microvascular complication. Increased risk from pregnancy induced hypertension without proteinuria and with proteinuria (pre-eclampsia) relates mainly to the association with kidney disease in diabetes, and poor glycemic control. A history of pre-eclampsia or pregnancy induced hypertension is an important prognostic factor for micro- and macro-vascular complications later in life. Data regarding the long-term effects of hypertensive pregnancies on late complications of diabetes suggest that women with diabetes should be monitored regularly and nephroprotective treatment initiated early. PMID- 26258814 TI - The parasitic plant Cuscuta australis is highly insensitive to abscisic acid induced suppression of hypocotyl elongation and seed germination. AB - Around 1% of angiosperms are parasitic plants. Their growth and development solely or partly depend on host plants from which they extract water, nutrients, and other molecules using a parasitic plant-specific organ, the haustorium. Strong depletion of nutrients can result in serious growth retardation and in some cases, death of the hosts. The genus Cuscuta (dodder) comprises about 200 holoparasitic species occurring on all continents. Their seedlings have no roots and cotyledons but are only string-like hypocotyls. When they contact suitable host plants, haustoria are formed and thereafter seedlings rapidly develop into vigorously growing branches without roots and leaves. This highly specialized lifestyle suggests that Cuscuta plants likely have unique physiology in development and stress responses. Using germination and seedling growth assays, we show that C. australis seeds and seedlings are highly insensitive to abscisic acid (ABA). Transcriptome analysis and protein sequence alignment with Arabidopsis, tomato, and rice homologs revealed that C. australis most likely consists of only four functional ABA receptors. Given that Cuscuta plants are no longer severely challenged by drought stress, we hypothesize that the ABA mediated drought resistance pathway in Cuscuta spp. might have had degenerated over time during evolution. PMID- 26258816 TI - Mining for Murder-Suicide: An Approach to Identifying Cases of Murder-Suicide in the National Violent Death Reporting System Restricted Access Database. AB - The National Violent Death Reporting System (NVDRS) is a United States Centers for Disease Control and Prevention (CDC) database of violent deaths from 2003 to the present. The NVDRS collects information from 32 states on several types of violent deaths, including suicides, homicides, homicides followed by suicides, and deaths resulting from child maltreatment or intimate partner violence, as well as legal intervention and accidental firearm deaths. Despite the availability of data from police narratives, medical examiner reports, and other sources, reliably finding the cases of murder-suicide in the NVDRS has proven problematic due to the lack of a unique code for murder-suicide incidents and outdated descriptions of case-finding procedures from previous researchers. By providing a description of the methods used to access to the NVDRS and coding procedures used to decipher these data, the authors seek to assist future researchers in correctly identifying cases of murder-suicide deaths while avoiding false positives. PMID- 26258817 TI - Anthropometric Injury Risk Factors in Elite-standard Youth Soccer. AB - The aim of the study was to investigate whether an increased risk of injury occurrence can be determined through frequent anthropometric measurements in elite-standard youth soccer players. Over the course of one season, we followed 101 male elite-standard youth soccer players between 11 and 19 years of age. Height and body mass were monitored at monthly measurement intervals and fat percentage was assessed every 3 months by use of the sum of skinfold method. Growth in height (cm), alternations in body mass index (kg/m(2)), fat percentage and fat-free mass index (kg/m(2)) were calculated. Injuries were recorded in accordance with the recommendations of the FIFA Consensus Model for Injury Registration. Odds ratio scores and 95% confidence intervals were calculated using binary logistic regression analyses. The following anthropometric injury risk factors were identified: >= 0.6 centimeter growth per month (p=0.03; OR=1.63; 95% CI: 1.06-2.52), >= 0.3 kg/m(2) increase of body mass index value per month (p=0.03; OR=1.61; 95% CI: 1.04-2.49) and low fat percentage; i. e., < 7% for players aged 11-16 and < 5% for players over 16 years (p=0.01; OR=1.81; 95% CI: 1.18-2.76). Individual monitoring of anthropometrics provides useful information to determine increased risk of injury occurrence in elite-standard youth soccer. PMID- 26258815 TI - Islet Oxygen Consumption Rate (OCR) Dose Predicts Insulin Independence in Clinical Islet Autotransplantation. AB - BACKGROUND: Reliable in vitro islet quality assessment assays that can be performed routinely, prospectively, and are able to predict clinical transplant outcomes are needed. In this paper we present data on the utility of an assay based on cellular oxygen consumption rate (OCR) in predicting clinical islet autotransplant (IAT) insulin independence (II). IAT is an attractive model for evaluating characterization assays regarding their utility in predicting II due to an absence of confounding factors such as immune rejection and immunosuppressant toxicity. METHODS: Membrane integrity staining (FDA/PI), OCR normalized to DNA (OCR/DNA), islet equivalent (IE) and OCR (viable IE) normalized to recipient body weight (IE dose and OCR dose), and OCR/DNA normalized to islet size index (ISI) were used to characterize autoislet preparations (n = 35). Correlation between pre-IAT islet product characteristics and II was determined using receiver operating characteristic analysis. RESULTS: Preparations that resulted in II had significantly higher OCR dose and IE dose (p<0.001). These islet characterization methods were highly correlated with II at 6-12 months post IAT (area-under-the-curve (AUC) = 0.94 for IE dose and 0.96 for OCR dose). FDA/PI (AUC = 0.49) and OCR/DNA (AUC = 0.58) did not correlate with II. OCR/DNA/ISI may have some utility in predicting outcome (AUC = 0.72). CONCLUSIONS: Commonly used assays to determine whether a clinical islet preparation is of high quality prior to transplantation are greatly lacking in sensitivity and specificity. While IE dose is highly predictive, it does not take into account islet cell quality. OCR dose, which takes into consideration both islet cell quality and quantity, may enable a more accurate and prospective evaluation of clinical islet preparations. PMID- 26258818 TI - Remnant Repair-enhanced Polyethylene Terepthalate Artificial Ligament Graft Ligamentization. AB - The aim of this study was to investigate whether augmented remnant repair could enhance polyethylene terepthalate (PET) artificial ligament graft ligamentization. 12 female goats underwent ACL reconstruction with PET artificial ligament graft in the right knees. Right knees in 6 goats were reconstructed with augmented remnant repair (Remnant group), whereas the other 6 goats had no augmented remnant repair comprised the Control group. 3 goats in each group were randomly sacrificed at 6 months and 12 months respectively after surgery. The intra-articular parts of the reconstructed grafts were harvested for histological evaluation. Well-vascularized tissue ingrowth within the artificial ligament was observed in the remnant group at 12 months postoperatively. Collagen-I content of graft was significantly higher in the Remnant group than in the Control group at each time point (p<0.05). The relative expression of collagen-III positive area of the remnant-preserved group was significantly higher than that of the Control group at 12 months (p=0.005). The vascular endothelial growth factor (VEGF) positive or CD31-positive area in the graft appeared higher in the Remnant group compared with the Control group at 6 months. Remnant repair enhanced the revascularization and remodeling of the PET artificial ligament in ACL reconstruction. PMID- 26258819 TI - Habitual Physical Activity, Sedentary Behaviour and Bone Health in Rheumatoid Arthritis. AB - Associations between habitual physical activity levels and bone health in rheumatoid arthritis (RA) were assessed. Twenty nine female patients with RA were assessed for bone mineral density (BMD), and classified as having low or normal hip BMD. Habitual physical activity levels were assessed using accelerometry, and disease activity was assessed using the Clinical Disease Activity Index (CDAI). Twenty one patients had normal bone mass, while 8 had low bone mass. There was no difference in age in the normal bone mass group (51(8)) compared to the low bone mass group (57(12)), p=0.19. Patients with normal bone mass spent on average 2 h less per day in sedentary activity (65(4)% vs. 73(2)%, p<0.01), over 70 min more time in light activity (23(1)% vs. 18(2)%, p<0.01), and over 50 min more in moderate activity per day (12(3)% vs. 8(2)%, p<0.01) than did patients with low bone mass, independently of disease activity or duration. Patients with normal bone mass broke up their sedentary time more frequently per day (72(21) vs. 53(18) times per day, p=0.03). The results of this study indicate that higher habitual activity levels may be protective of bone health in patients with RA, and should be encouraged. PMID- 26258820 TI - The Acute Effect of Fast and Slow Stepping Cadence on Regional Vascular Function. AB - The aim of this study was to determine if stepping cadence when controlling for total steps has a differential impact on regional vascular function. 16 young adults (21+/-2 years) performed fast (125 steps per min) and slow (80 steps per min) walking for a total of 3 000 steps on separate days. Doppler ultrasound was used to measure compliance, blood flow and shear rate of the common carotid artery and superficial femoral artery before walking and at 30 and 60 min after walking. Carotid compliance was significantly (p<0.05) elevated 60 min after fast (17.1+/-25.9%) and slow (24.1+/-27.3%) walking with no difference between cadences. Both fast and slow walking failed to increase femoral compliance, despite significant (p<0.05) dilation in the femoral artery that was observed at 30 (4.2+/-3.9%) and 60 min (3.9+/-5.4%) after fast walking. Consistent with this latter finding, femoral blood flow and shear rate were significantly (p<0.05) increased at 30 min after fast walking. These results indicate that a single bout of walking at a fast or slow stepping cadence increases compliance of large elastic arteries but has no acute effect on compliance of peripheral (leg) arteries. PMID- 26258821 TI - Antioxidants may Attenuate Plasma Erythropoietin Decline after Hyperbaric Oxygen Diving. AB - According to previous studies, plasma erythropoietin (EPO) may decrease after hyperbaric oxygen exposure due to oxidative stress. It is hypothesized that the decrease of EPO can be attenuated by oxygen free radical scavengers.The aim of the present study was to evaluate whether EPO plasma levels can be influenced by oral application of vitamin C and E before repeated hyperbaric oxygen exposure during diving. 16 healthy male police task force divers performed 3 morning dives on oxygen within a regular diving schedule on 3 consecutive days. They were randomized into either the placebo group or the vitamin group, receiving 1 g ascorbic acid and 600 IU D-alpha-tocopherol orally 60 min before the dive. Blood samples for EPO measurement were taken on days 1, 2, and 3 at T1, T3 and T5 60 min before and at T2, T4 and T6 60 min after each dive, respectively. A moderate decrease of EPO was observed beginning at T3 until T6 in the placebo group. The EPO concentrations in the vitamin group did not show relevant variations compared to baseline. Radical scavenging vitamins C and D may counteract hyperbaric oxygen related mechanisms reducing EPO production in hyperbaric oxygen exposure during diving. PMID- 26258822 TI - Changes in Kidney Functions during Middle-distance Triathlon in Male Athletes. AB - Strenuous exercise induces proteinuria which is related to the intensity of exercise. However, renal responses to each type of exercise during a middle distance triathlon have not been reported. The present study, carried out on 7 healthy athletes, investigated renal function at rest and after each exercise of a half-triathlon race. Blood and urine samples were collected at rest and after each specific event. Protein excretion and renal clearances were determined on each sample. Compared with resting values, albuminuria was increased by a factor of 30 (p<0.05) after swimming but did not differ from the resting value after cycling and running (p>0.05). Rates of beta2-microglobulin and retinol-binding protein excretion did not change throughout the triathlon (p>0.05). Glomerular filtration rate (expressed as creatinine clearance) remained stable after each exercise event, whereas tubular reabsorption rate (expressed as urea clearance) was reduced by 50, 40 and 65% after swimming, cycling and running, respectively, compared to pre-exercise values (p<0.05). Glomerular membrane permeability (expressed as albumin clearance) was significantly increased by the swimming event (13 times, p<0.05). These results suggest that middle-distance triathlon has a noticeable impact on the glomerular membrane permeability (albumin clearance) and elimination of protein waste (urea clearance) depending on exercise type. PMID- 26258823 TI - Reliability of the Heart Rate Variability Threshold using Visual Inspection and Dmax Methods. AB - The purpose of this study was to compare heart rate variability threshold (HRVT) in 6 incremental tests and test its reproducibility using visual inspection and Dmax methods for root mean square of successive differences between the adjacent normal R-R intervals (RMSSD), standard deviation of the normal RR interval (SDNN) and standard deviation of instantaneous beat-to-beat variability (SD1). 12 adult males performed an incremental test to volitional fatigue on a cycle simulator during 6 visits to the laboratory. The initial test load was 25 W, and the intensity was increased by 25 W every 3 min until volitional fatigue set in. The HRV during the incremental test was analyzed using the RMSSD, SDNN and SD1 indices and the determination of HRVT was performed using 2 methods: visual inspection and Dmax. The results demonstrated that the SD1 and RMSSD indices, determined by the visual inspection method, presented the highest reproducibility of HRVT when compared with the other indices and methods. We concluded that the best method for determining HRVT was the technique using the point of stabilization by visual inspection in the SD1 and RMSSD indices during the incremental test, due to its high reproducibility, lower coefficient of variation and increment size. PMID- 26258824 TI - Imposed Cold-water Ingestion during Open Water Swimming in Internationally Ranked Swimmers. AB - The authors explored the effects of open water swimming in a tropical environment on both core temperature (T c) and thermal perceptions of high-level swimmers during an official international 10-km race and two 5-km swimming tests. The swimmers drank neutral water (i. e., 28.0+/-3.0 degrees C) ad libitum every 2,000 m during Competition, whereas the ingested volume was imposed in the 5-km tests: every 1,000 m, they drank 190 mL of cold water (CW, 1.1+/-0.7 degrees C) or neutral water (NW, 28.0+/-3.0 degrees C). They also self-rated their thermal comfort and sensation (TC and TS), and their T c was recorded. The study demonstrated that adequate fluid intake significantly decreased T c in swimmers swimming at race pace in hot water (i. e., 37.5+/-0.3 degrees C vs. 38.3+/-0.4 degrees C, in NW vs. Competition, respectively). This effect was more pronounced with cold water (i. e., 36.7+/-1.1 degrees C, in CW). No significant changes were noted in mean heart rate (i. e., 145+/-5, 143+/-4 and 141+/-5 bpm for NW, CW and Competition, respectively). Further studies are needed to explore the effect of this cooling method on the performances of international swimmers during tropical swimming events. PMID- 26258825 TI - Skeletal Maturation and Aerobic Performance in Young Soccer Players from Professional Academies. AB - The contribution of chronological age, skeletal age (Fels method) and body size to variance in peak velocity derived from the Carminatti Test was examined in 3 competitive age groups of Brazilian male soccer players: 10-11 years (U-12, n=15), 12-13 years (U-14, n=54) and 14-15 years (U-16, n=23). Body size and soccer-specific aerobic fitness were measured. Body composition was predicted from skinfolds. Analysis of variance and covariance (controlling for chronological age) were used to compare soccer players by age group and by skeletal maturity status within of each age group, respectively. Relative skeletal age (skeletal age minus chronological age), body size, estimated fat free mass and performance on the Carminatti Test increased significantly with age. Carminatti Test performance did not differ among players of contrasting skeletal maturity status in the 3 age groups. Results of multiple linear regressions indicated fat mass (negative) and chronological age (positive) were significant predictors of peak velocity derived from the Carminatti Test, whereas skeletal age was not a significant predictor. In conclusion, the Carminatti Test appears to be a potentially interesting field protocol to assess intermittent endurance running capacity in youth soccer programs since it is independent of biological maturity status. PMID- 26258826 TI - Critical Power in Laboratory and Field Conditions Using Single-visit Maximal Effort Trials. AB - To compare critical power (CP) and the maximum work performed above CP (W') obtained from a single-visit laboratory test with a single-visit field test, 10 trained cyclists (VO(2max) 63.2+/-5.5 mL.min(-1).kg(-1)) performed a laboratory and a field test. The laboratory test consisted of 3 trials to exhaustion between 2-15 min and the field test comprised 3 maximal efforts of 2, 6 and 12 min, where power output was measured using a mobile power meter. CP and W' were estimated using 3 mathematical models (hyperbolic, linear work-time, linear power -1/time). The agreement between laboratory and field conditions was assessed with the 95% limits of agreement (LoA). CP was not significantly different between laboratory (280+/-33 W) and field conditions (281+/-28 W) (P=0.950). W' was significantly higher in laboratory (21.6+/-7.1 kJ) compared to field conditions (16.3+/-7.4 kJ) (P=0.013). The bias was -2.8+/-27 W (95% LoA: -55 to 50 W) and 6.4+/-5.1 kJ (95% LoA: -3.5 to 16.4 kJ) for CP and W', respectively. No differences between the mathematical models were found for CP and W' (P=0.054-1.000). Although CP was not significantly different between conditions, a high random variation does not support its interchangeable use. The mathematical model used has no influence on estimates of CP and W'. PMID- 26258828 TI - Clinical Practicums: More Than Finding a Preceptor. PMID- 26258829 TI - Alarm Safety. PMID- 26258830 TI - A New Era of Nursing in Indonesia and a Vision for Developing the Role of the Clinical Nurse Specialist. PMID- 26258831 TI - Psychometric Properties of the Multidimensional Scale of Perceived Social Support. PMID- 26258832 TI - Waiting for the Antidote: The Journey of Idarucizumab as a Potential Specific Reversal Agent for Dabigatran (Pradaxa). PMID- 26258833 TI - Mini-Mental State Examination for the Detection of Alzheimer Disease and Other Dementias in People With Mild Cognitive Impairment. PMID- 26258834 TI - Presenting With Power. PMID- 26258835 TI - Implementation of a Nursing Peer-Review Program in the Hospital Setting. AB - PURPOSE/OBJECTIVES: Nursing peer review (NPR), a formal process by which nurses are referred for peer evaluation when patient care problems are identified, has gained acceptance as a method to improve nursing quality and safety. This article describes the development of a formal NPR program for acute care nurses, intended to validate and improve nursing practice. BACKGROUND: Nursing peer review is a systematic process of assessing and evaluating nursing care by peers against professional practice standards. The purpose of an NPR program is to provide a pathway whereby peers hold one another accountable for practice. RATIONALE: Accountability is an important demonstrator of professionalism. Because nursing is a trusted profession, it is imperative that it demonstrate accountability. DESCRIPTION: The NPR program was developed and implemented by a clinical nurse specialist. A literature review was conducted to assist program development including the processes of building an NPR committee and nurses for review. To trigger referrals to the NPR system, nursing indicators were identified. To diminish fear among nurses, education for staff members focused on the purpose and importance of the NPR process and the intent to strengthen practice. Nursing peer review committee members were also educated in the use of NPR principles including just culture, appreciative inquiry, and confidentiality. OUTCOME: Upon implementation, nearly 200 referrals were received within the first 14 months; 85% met criteria for review. Nursing practice was identified as appropriate (ie, nursing actions were consistent with good practice) in 66% of the reviews. Trends in individual and system processes were identified for improvement. CONCLUSION/IMPLICATIONS: The clinical nurse specialist's role as NPR program coordinator provided an innovative way to impact nursing and organizational spheres of influence through program development and implementation. Future goals include sustaining/improving nursing awareness of the NPR process and identification of additional indicators to trigger review. PMID- 26258836 TI - Clinical Nurse Specialist Collaboration to Recognize, Prevent, and Treat Pediatric Pressure Ulcers. AB - PURPOSE/OBJECTIVES: The purpose of this quality improvement project was to reduce the incidence of pressure ulcers in a 232-bed, freestanding children's hospital in Western United States. BACKGROUND: Pressure ulcers have been an underappreciated hospital-acquired condition in children. Children have distinct anatomic, physiologic, and developmental factors that alter how pressure ulcers occur, but nurses may not recognize the pediatric patient as at risk because of lack of knowledge and tools to assess skin, identify risk factors, and recognize or stage pressure ulcers. Our initial efforts to develop organizational tools to reduce pediatric pressure ulcers were not sufficient, despite improvements in care. Interprofessional and intraprofessional collaboration, led by clinical nurse specialists, focused on documentation, tracheostomies, respiratory devices, and hemodynamically unstable or extracorporeal life support patients. RATIONALE: Stage 3 and 4 and unstageable pressure ulcers are also "never events" in children. The unique factors involved with infant and pediatric pressure ulcers demand unique solutions. OUTCOME: Our collaborative efforts led to a significant and sustained reduction in pressure ulcer incidence, from 3.3 per 1000 patient days in the first quarter of 2010 to 1.7 per 1000 patient days in the second quarter of 2014. Reportable pressure ulcers were reduced by 60%. Improved awareness and prevention strategies also led to significant reductions in extracorporeal life support patient pressure ulcers and respiratory device related pressure ulcers. CONCLUSION: Through intraprofessional and interprofessional collaboration, the clinical nurse specialists were able to implement sustained organizational change and improve care for infants and children. IMPLICATIONS: Reduction in pressure ulcers is achievable but requires collaboration and creative solutions that involve multiple disciplines. PMID- 26258837 TI - Improving Outcomes for High-Risk Patients: Creating Timely Reports From the Electronic Health Record. AB - PURPOSE/OBJECTIVES: This article describes a stepwise model to develop timely reports from the electronic health record (EHR), which can be used to improve outcomes for high-risk patients. BACKGROUND: The literature is beginning to describe the use of reports and decisional support tools to identify high-risk populations to affect outcomes. The clinical nurse specialist is in a unique position to optimize use of the EHR to create reports and decisional supports to improve individual nursing practice, standardize clinical workflows, and enhance patient outcomes. RATIONALE: These reports identify patients at high risk for complications and can be utilized by the clinical nurse specialist to implement targeted interventions early in the patient's hospital stay, resulting in improved outcomes for selected patient populations. DESCRIPTION: A stepwise process used to develop these clinical informational reports is described as a model that is clinically relevant to a wide range of clinical nurse specialist roles, populations, and settings who use EHR. OUTCOMES: This model was utilized to create reports to target the highest-risk patients in the organization including patients with high fall risk, alcohol withdrawal syndrome, and the need for sitters. CONCLUSIONS: The basic idea of reports described by this model can significantly alter healthcare outcomes by making it possible for clinicians to adjust the way patient data are viewed at the bedside. These reports assist the clinical nurse specialist in reducing patient safety events, transfers to higher levels of care, sitter usage, or readmissions IMPLICATIONS: : Clinical nurse specialists can create reports targeting highest-risk patients in the organization and address reportable outcomes resulting in improvement in both financial and patient outcomes. This model can also bring relevance, value, and visibility to the clinical nurse specialist within the system by placing the clinical experts at the bedside of greatest need. PMID- 26258838 TI - Radiation via Intracavitary-Interstitial Pelvic Implants for Gynecological Cancers: Clinical Nurse Specialists Affecting Change. AB - PURPOSE/OBJECTIVES: This article describes the value of a clinical nurse specialist (CNS) team in partnering with interdisciplinary stakeholders to improve care for women with gynecological cancers receiving radiation via intracavitary-interstitial pelvic implants (IPI). BACKGROUND: Intracavitary interstitial pelvic implants can prolong survival but is associated with significant impacts on quality of life. Intracavitary-interstitial pelvic implants is a complex and invasive intervention that requires patients to be immobile for 3 days and creates challenges related to dignity, hygiene, nutrition, pain management, emotional health, skin care, and overall patient satisfaction. The nursing staff shared concerns with their respective CNSs regarding patients' quality of care. Lack of standardized practice/orders and gaps in knowledge created challenges. RATIONALE: Clinical nurse specialist practice requires collaborative efforts within the 3 spheres of influence to improve the care of patients receiving IPI therapy. DESCRIPTION: The CNSs recognized and addressed needs of patients/families, staff, and the organization across the continuum. The team's efforts relied on reflection of nurses' concerns, collaboration, and a unified vision for exceptional care. OUTCOMES: This CNS-led initiative was successful in establishing processes to ensure quality care. Improvement in patient care was achieved through creation of standardized order sets, a focused plan of care, and patient/family/staff education. Nurse satisfaction, confidence, and empowerment to provide patient care with dignity and sensitivity have been verbalized. CONCLUSION: The CNS team's broad scope of practice, across inpatient, outpatient, and evidence-based practice, is a strength. Key to the team's success was the recognition of challenges and a unified vision to bring together stakeholders to facilitate improvement of care. Future direction includes evaluating nutritional choices and examining psychosocial aspects of the patient's experience. An interdisciplinary nursing grand rounds is planned to highlight the outcomes of this team. IMPLICATIONS: The leadership of CNS teams with varied scopes is critical to affecting change within the spheres of influence and improving patient care across the continuum. PMID- 26258839 TI - A Healing, Restorative, Life-Enhancing Environment in 1900: The Free Hospital for Women in Brookline, Massachusetts. PMID- 26258840 TI - Complexities of Medication Management Across Care Transitions: A Case Report. AB - PURPOSE: The purpose of this article is to identify medication-related considerations for clinical nurse specialist practice by presenting a case report detailing the complexities of medication management, unresolved medication discrepancies, and reconciliation across care transitions. BACKGROUND: Care transitions are a vulnerable time for medication-related problems to occur. Unresolved medication discrepancies can lead to adverse drug events and other poor health outcomes, including hospital readmissions and increased healthcare costs. Reconciling medication discrepancies during care transitions has been identified as a national patient safety goal to prevent medication-related problems. Clinical nurse specialists are uniquely qualified to lead and manage efforts to mitigate these problems during care transitions. CASE PRESENTATION: A 72-year-old male patient diagnosed with oral cancer underwent 8 weeks of chemotherapy and radiation treatments. Throughout these 8 weeks, the patient was seen by 4 providers and admitted to the hospital for neutropenia. As a result, a total of 19 new medications were prescribed and 5 medications were discontinued. Medication reconciliation was completed at each visit and at admission and discharge at the hospital. At discharge, the patient's medication regimen was complex, with 38 separate doses of 17 different medications per 24-hour period. Understanding and organizing the daily medication regimen were a consistent challenge for the patient during his illness. DISCUSSION: This case highlights the complexities of medication regimens and opportunities to improve medication management and reconciliation across care transitions. This case underscores the need for and importance of quality patient-provider communication, assessing and managing medication regimen complexity, evaluating medications against the American Geriatrics Society Beers Criteria, evaluating potential drug-drug or drug-food interactions, and recognizing at-risk behaviors that may lead to medication discrepancies and errors at care transitions. Potential opportunities where clinical nurse specialists could intervene to promote safe and effective medication management across care transitions are presented. CONCLUSION/IMPLICATIONS: Clinical nurse specialists have the unique ability to make key contributions and influence medication management and reconciliation across care transitions to promote medication effectiveness and safety. PMID- 26258842 TI - A Pilot Study on the Combination of Applied Behavior Analysis and Bumetanide Treatment for Children with Autism. AB - OBJECTIVE: The purpose of this study was to investigate the therapeutic effects of combined bumetanide and applied behavior analysis (ABA) treatment in children with autism. METHODS: Sixty children diagnosed with autism according to the International Classification of Diseases, Tenth Revision (ICD-10) criteria (mean age of 4.5 years) were randomly divided into two groups: A single treatment group (n=28) and a combined treatment group (n=32). The combined treatment group received ABA training combined with oral bumetanide (0.5 mg twice a day). The single treatment group received ABA training only. Autism symptoms were evaluated with the Autism Behavior Checklist (ABC) and the Childhood Autism Rating Scale (CARS), whereas severity of disease (SI) and global improvement (GI) were measured with the Clinical Global Impressions (CGI). Assessment of ABC, CARS, and CGI was performed immediately before and 3 months after initiation of the treatment(s). RESULTS: Prior to intervention(s) no statistically significant differences in scores on the ABC, CARS, SI, or GI were found between the two groups. Total scores of the ABC, CARS, and SI were decreased in both groups after 3 months (p<0.05) compared with the scores prior to treatment. The total scores of the ABC and the CGI were significantly (p<0.05) lower in the combined treatment group than in the single treatment group. Although the total and item scores of the CARS in the combined treatment group were lower than in the single treatment group after a 3 month intervention, they did not reach statistical significance. No adverse effects of bumetanide were observed. CONCLUSIONS: Treatment with bumetanide combined with ABA training may result in a better outcome in children with autism than ABA training alone. PMID- 26258843 TI - Heparin versus DNA: Chiral Preferences in Polyanion Binding to Self-Assembled Multivalent (SAMul) Nanostructures. AB - This communication presents simple cationic self-assembling multivalent (SAMul) first generation dendrons based on L or D lysine, which form identical nanoscale assemblies in terms of dimensions and charge densities but toward which DNA and heparin exhibit different chiral binding preferences. However, higher generation dendrons with larger hydrophilic head groups are bound identically by these polyanions, irrespective of chirality. We propose that well-organized chiral ligands on the surface of self-assembled nanostructures can exhibit enantioselective polyanion binding. This demonstrates that small structural changes can be amplified by self-assembly and impact on nanoscale binding. PMID- 26258844 TI - Rise of the Helix from a Collapsed Globule during the Folding of Monellin. AB - Early kinetic intermediates observed during the folding of many proteins are invariably compact and appear to possess some secondary structure. Consequently, it has been difficult to understand whether compaction drives secondary structure formation or secondary structure formation facilitates compaction during folding. In this study of the folding of single-chain monellin, it is shown that a kinetic molten globule (MG) is populated at 2 ms of folding. Far-UV circular dichroism (CD) measurements show that the kinetic MG is devoid of any helical structure even under the most stabilizing folding conditions. Multisite fluorescence resonance energy transfer (FRET) measurements show that the kinetic MG is compact with different segments having contracted to different extents. It is shown that the sequence segment that goes on to form the sole helix in the native protein is fully collapsed in the kinetic MG. This segment expands to accommodate the helix as the kinetic MG folds further to the native state, while other segments of the protein contract. Helix formation starting from the kinetic MG is shown to occur in multiple kinetic steps, whether measured by far-UV CD or by FRET. PMID- 26258845 TI - Widespread non-additive and interaction effects within HLA loci modulate the risk of autoimmune diseases. AB - Human leukocyte antigen (HLA) genes confer substantial risk for autoimmune diseases on a log-additive scale. Here we speculated that differences in autoantigen-binding repertoires between a heterozygote's two expressed HLA variants might result in additional non-additive risk effects. We tested the non additive disease contributions of classical HLA alleles in patients and matched controls for five common autoimmune diseases: rheumatoid arthritis (ncases = 5,337), type 1 diabetes (T1D; ncases = 5,567), psoriasis vulgaris (ncases = 3,089), idiopathic achalasia (ncases = 727) and celiac disease (ncases = 11,115). In four of the five diseases, we observed highly significant, non-additive dominance effects (rheumatoid arthritis, P = 2.5 * 10(-12); T1D, P = 2.4 * 10( 10); psoriasis, P = 5.9 * 10(-6); celiac disease, P = 1.2 * 10(-87)). In three of these diseases, the non-additive dominance effects were explained by interactions between specific classical HLA alleles (rheumatoid arthritis, P = 1.8 * 10(-3); T1D, P = 8.6 * 10(-27); celiac disease, P = 6.0 * 10(-100)). These interactions generally increased disease risk and explained moderate but significant fractions of phenotypic variance (rheumatoid arthritis, 1.4%; T1D, 4.0%; celiac disease, 4.1%) beyond a simple additive model. PMID- 26258846 TI - Genomic spectra of biliary tract cancer. AB - The incidence of biliary tract cancer (BTC), including intrahepatic (ICC) and extrahepatic (ECC) cholangiocarcinoma and gallbladder cancer, has increased globally; however, no effective targeted molecular therapies have been approved at the present time. Here we molecularly characterized 260 BTCs and uncovered spectra of genomic alterations that included new potential therapeutic targets. Gradient spectra of mutational signatures with a higher burden of the APOBEC associated mutation signature were observed in gallbladder cancer and ECC. Thirty two significantly altered genes, including ELF3, were identified, and nearly 40% of cases harbored targetable genetic alterations. Gene fusions involving FGFR2 and PRKACA or PRKACB preferentially occurred in ICC and ECC, respectively, and the subtype-associated prevalence of actionable growth factor-mediated signals was noteworthy. The subgroup with the poorest prognosis had significant enrichment of hypermutated tumors and a characteristic elevation in the expression of immune checkpoint molecules. Accordingly, immune-modulating therapies might also be potentially promising options for these patients. PMID- 26258847 TI - Genomic analysis of mycosis fungoides and Sezary syndrome identifies recurrent alterations in TNFR2. AB - Mycosis fungoides and Sezary syndrome comprise the majority of cutaneous T cell lymphomas (CTCLs), disorders notable for their clinical heterogeneity that can present in skin or peripheral blood. Effective treatment options for CTCL are limited, and the genetic basis of these T cell lymphomas remains incompletely characterized. Here we report recurrent point mutations and genomic gains of TNFRSF1B, encoding the tumor necrosis factor receptor TNFR2, in 18% of patients with mycosis fungoides and Sezary syndrome. Expression of the recurrent TNFR2 Thr377Ile mutant in T cells leads to enhanced non-canonical NF-kappaB signaling that is sensitive to the proteasome inhibitor bortezomib. Using an integrative genomic approach, we additionally discovered a recurrent CTLA4-CD28 fusion, as well as mutations in downstream signaling mediators of these receptors. PMID- 26258848 TI - A gene-based association method for mapping traits using reference transcriptome data. AB - Genome-wide association studies (GWAS) have identified thousands of variants robustly associated with complex traits. However, the biological mechanisms underlying these associations are, in general, not well understood. We propose a gene-based association method called PrediXcan that directly tests the molecular mechanisms through which genetic variation affects phenotype. The approach estimates the component of gene expression determined by an individual's genetic profile and correlates 'imputed' gene expression with the phenotype under investigation to identify genes involved in the etiology of the phenotype. Genetically regulated gene expression is estimated using whole-genome tissue dependent prediction models trained with reference transcriptome data sets. PrediXcan enjoys the benefits of gene-based approaches such as reduced multiple testing burden and a principled approach to the design of follow-up experiments. Our results demonstrate that PrediXcan can detect known and new genes associated with disease traits and provide insights into the mechanism of these associations. PMID- 26258850 TI - Photoinduced Electron-Transfer-Based Hybridization Probes for Detection of DNA and RNA. AB - Here, we report the synthesis of a hybridization probe for detection of RNA and DNA based on photoinduced electron transfer (PeT). We designed and synthesized an oligonucleotide containing an adenosine analogue with a 9-(N,N dimethylaminomethyl)anthracenyl moiety at its 6-position via an ethynylene linker as the hybridization probe. When the probe was hybridized with a complementary RNA or DNA, the fluorescence intensity increased 3-fold or 4.5-fold, respectively, compared to the single-stranded state. PMID- 26258849 TI - An APOBEC3A hypermutation signature is distinguishable from the signature of background mutagenesis by APOBEC3B in human cancers. AB - Elucidation of mutagenic processes shaping cancer genomes is a fundamental problem whose solution promises insights into new treatment, diagnostic and prevention strategies. Single-strand DNA-specific APOBEC cytidine deaminase(s) are major source(s) of mutation in several cancer types. Previous indirect evidence implicated APOBEC3B as the more likely major mutator deaminase, whereas the role of APOBEC3A is not established. Using yeast models enabling the controlled generation of long single-strand genomic DNA substrates, we show that the mutation signatures of APOBEC3A and APOBEC3B are statistically distinguishable. We then apply three complementary approaches to identify cancer samples with mutation signatures resembling either APOBEC. Strikingly, APOBEC3A like samples have over tenfold more APOBEC-signature mutations than APOBEC3B-like samples. We propose that APOBEC3A-mediated mutagenesis is much more frequent because APOBEC3A itself is highly proficient at generating DNA breaks, whose repair can trigger the formation of single-strand hypermutation substrates. PMID- 26258851 TI - Ectopic osteogenesis and scaffold biodegradation of nano-hydroxyapatite-chitosan in a rat model. AB - The bone-formation and scaffold-biodegradation processes have not been fully characterized. This study aimed to determine the osteogenic ability of nHA-CS osteo-induced bone marrow mesenchymal stem cell (BMSC) composites and to explore the relationship between bone formation and scaffold biodegradation. The nHA-CS osteo-induced BMSC composites (nHA-CS+cells group) and the nHA-CS scaffolds (nHA CS group) were implanted into the femoral spatium intermusculare of SD rats. At 2, 4, 6, 8, and 12 weeks post-implantation, the rat femurs were scanned using computerized tomography (CT), and the CT values of the implants were measured and comparatively analyzed. The implants were then harvested and subjected to hematoxylin and eosin (HE) and Masson's trichrome staining, and the percentages of bone area, scaffold area and collagen area were compared between the two groups. The CT values of the implants were higher in the nHA-CS+cells group than the nHA-CS group at the same time points (P < 0.05). Histological analysis revealed that de novo bone and collagen formation in the pores of the scaffolds gradually increased from 2 weeks post-implantation in both groups and that the scaffold gradually degraded as bone formation proceeded. However, more de novo bone and collagen formation and scaffold degradation occurred in the nHA-CS+cells group than in the nHA-CS group at the same time points (P < 0.05). In conclusion, nHA-CS osteo-induced BMSC composites are promising bone tissue engineering substitutes, and osteo-induced BMSCs can significantly enhance the osteogenic ability and play an active role in the degradation of nHA-CS scaffolds on par with bone formation. PMID- 26258853 TI - The Relationships between Age and Running Biomechanics. AB - Running has high injury rates, especially among older runners. Most aging literature compares young with old runners without accounting for the progression of biomechanics throughout the lifespan. We used age as a continuous variable to investigate the continuum of age-related gait adaptations in running along with determining the chronology and rate of these adaptations. PURPOSE: This study aimed to identify the relations among age and selected running biomechanics throughout the range of 18-60 yr. METHODS: Experienced (n = 110) healthy runners (male, 54%) provided informed consent and ran at their training pace while motion and force data were captured. Kinematics, ground reaction forces (GRF), and lower limb joint torques and powers were correlated with age using Pearson product moment correlations and linear regression. RESULTS: Running velocity was inversely related to age (r = -0.27, P = 0.005) because of decreased stride length (r = -0.25, P = 0.008) but not rate. Peak vertical GRF (r = -0.23, P = 0.016) and peak horizontal propulsive GRF decreased with age (r = -0.38, P < 0.0001). Peak ankle torque (r = -0.32, P = 0.0007) and peak negative (r = 0.34, P = 0.0003) and positive (r = -0.37, P < 0.0001) ankle power decreased with age. Age-based regression equations and per-year reductions in all variables significantly related to age are reported. CONCLUSIONS: Data support previous work showing lower GRF, stride length, and velocity in old runners. Results are novel in showing the rate of decline in running biomechanics on a per-year basis and that mechanical reductions at the ankle but not at the hip or knee were correlated with age, confirming a previous observation of biomechanical plasticity with age showing reduced ankle but not hip function in gait. PMID- 26258854 TI - High Cardiorespiratory Fitness Levels Slow the Decline in Peak Heart Rate with Age. AB - INTRODUCTION: Although it is well accepted that peak HR (HRpeak) decreases with age, there is no clear consensus on the rate of this decline and the influence of cardiorespiratory fitness (CRF) on the rate of decline. METHODS: Treadmill cardiopulmonary exercise test (CPET) results with RER >= 1.0 from participants (1849 men and 1469 women; 18-80 yr) of a university-based health assessment/fitness program were retrospectively examined using cross-sectional and longitudinal study designs. All subjects were free of overt cardiovascular disease and were not taking HR-altering medications. Only subjects having completed >= 2 cardiopulmonary exercise tests with >= 1 yr between test dates were included in the longitudinal analysis (418 men and 225 women). Subjects were categorized into CRF categories (high, moderate, and low) relative to age and gender normative classifications. A general linear-model univariate analysis was performed to test the effect of CRF on the decline in HRpeak with age. RESULTS: In both cross-sectional and longitudinal analyses, HRpeak declined at a significantly faster rate across the CRF categories (cross-sectional: -0.60, 0.78, and -0.87 bpm . yr(-1), respectively; longitudinal: -0.61, -0.82, and -1.02 bpm . yr(-1), respectively). CONCLUSIONS: This study provides evidence that the maintenance of a high or moderate CRF may slow the age-related decline in HRpeak in both men and women. The application of CRF-specific HRpeak prediction equations should be used to improve interpretation of HRpeak from exercise tests. PMID- 26258852 TI - Recent Advances in the Discovery of Norovirus Therapeutics. AB - Noroviruses are members of the family Caliciviridae. Norovirus infections are a global health burden that impacts >20 million individuals annually in the U.S. alone. Noroviruses are associated with high morbidity among vulnerable populations, particularly immunocompromised patients. This perspective highlights recent developments related to the discovery and development of norovirus specific small-molecule therapeutics as well as recent advances in our understanding of norovirus biology and pathogenesis. Most of the work in this area is at the early discovery stage and has been primarily focused on inhibitors of norovirus 3C-like protease and RNA dependent RNA polymerase. However, recent discoveries emanating from basic studies in norovirus research have resulted in the identification of new host-related drug targets that can be exploited. A repurposed compound has been advanced to human clinical studies. PMID- 26258855 TI - Acute Strength Training Increases Responses to Stimulation of Corticospinal Axons. AB - PURPOSE: Acute strength training of forearm muscles increases resting twitch forces from motor cortex stimulation. It is unclear if such effects are spinal in origin and if they also occur with training of larger muscles. With the use of subcortical stimulation of corticospinal axons, the current study examined if one session of strength training of the elbow flexor muscles leads to spinal cord changes and if the type of training is important. METHODS: In experiment 1, 10 subjects completed ballistic isometric training, ballistic concentric training, and no training (control) on separate days. In experiment 2, 13 subjects completed ballistic isometric training and slow-ramp isometric training. Before and after training, transcranial magnetic stimulation over the contralateral motor cortex elicited motor-evoked potentials (MEPs) in the resting biceps brachii, and electrical stimulation of corticospinal tract axons at the cervicomedullary junction elicited cervicomedullary motor-evoked potentials (CMEPs). Motor-evoked potential and CMEP twitch forces were also measured. RESULTS: In experiment 1, CMEPs and CMEP twitch forces were significantly facilitated after ballistic isometric training compared to control. In experiment 2, MEPs, MEP twitch forces, CMEPs, and CMEP twitch forces increased for 15 to 25 min after ballistic and slow-ramp isometric training. CONCLUSION: Via processes within the spinal cord, one session of strength training of the elbow flexors increases net output from motoneurons projecting to the trained muscles. Likely mechanisms include increased efficacy of corticospinal-motoneuronal synapses or increased motoneuron excitability. However, the rate of force generation during training is not important for inducing these changes. A concomitant increase in motor cortical excitability is likely. These short-term changes may represent initial neural adaptations to strength training. PMID- 26258856 TI - Effect of Plyometrics on the Energy Cost of Running and MHC and Titin Isoforms. AB - Several training strategies such as plyometrics have been shown to improve running economy; however, its physiological basis remains elusive. PURPOSE: To examine the effect of plyometric training on the energy cost of running (ECR, J . kg(-1) . min(-1)), titin, and myosin heavy chain (MHC) isoforms. METHODS: Subjects were randomly assigned to a 6-wk plyometric treatment (P; n = 11) or control group (C; n = 11). Preintervention and postintervention outcomes included body composition, vertical jump, sit-and-reach, maximal oxygen consumption (VO2max), speed at onset of blood lactate, 3-km time trial performance, ECR, and a vastus lateralis muscle biopsy for protein analysis. RESULTS: Plyometric intervention resulted in improved time trial (P, 2.6% faster, P = 0.04; C, 1.6%, P = 0.17). VO2max improved in the P group (5.2%, P = 0.03), whereas the C group increased by 3.1% (P = 0.20). The ECR decreased in the P group as the result of 6 wk of plyometric training (P = 0.02 for stage 3), whereas it increased in the C group (P = 0.02 for stage 3). The ECR correlated strongly with performance at stages 2, 3, and 4 (r > 0.8, P < 0.001) independent of group. There was no significant main effect of group, time, or interaction on any of the protein isoforms analyzed. A negative correlation was found between the ECR at stage 7 and MHC IIa (r = -0.96, P < 0.001), and the ECR at stage 6 with titin isoform 1 (T1)/T2 ratio (r = -0.69, P = 0.007) independent of group. CONCLUSION: Six weeks of plyometric training improved running performance and the ECR despite no measurable changes in MHC and titin isoforms. However, higher MHC IIa and lower T1/T2 isoform ratios correlated to lower ECR. PMID- 26258857 TI - Ice Slurry Ingestion Leads to a Lower Net Heat Loss during Exercise in the Heat. AB - PURPOSE: To compare the reductions in evaporative heat loss from the skin (Esk) to internal heat loss (Hfluid) induced by ice slurry (ICE) ingestion relative to 37 degrees C fluid and the accompanying body temperature and local thermoeffector responses during exercise in warm, dry conditions (33.5 degrees C +/- 1.4 degrees C; 23.7% +/- 2.6% relative humidity [RH]). METHODS: Nine men cycled at approximately 55% VO2peak for 75 min and ingested 3.2 mL . kg(-1) aliquots of 37 degrees C fluid or ICE after 15, 30, and 45 min of exercise. Metabolic heat production (M-W), rectal temperature (Tre), mean skin temperature (Tsk), whole-body sweat loss (WBSL), local sweat rate (LSR), and skin blood flow (SkBF) were measured throughout. Net heat loss (HLnet) and heat storage (S) were estimated using partitional calorimetry. RESULTS: Relative to the 37 degrees C trial, M-W was similar (P = 0.81) with ICE ingestion; however, the 200 +/- 20 kJ greater Hfluid (P < 0.001) with ICE ingestion was overcompensated by a 381 +/- 199-kJ lower Esk (P < 0.001). Net heat loss (HLnet) was consequently 131 +/- 120 kJ lower (P = 0.01) and S was greater (P = 0.05) with ICE ingestion compared with 37 degrees C fluid ingestion. Concurrently, LSR and WBSL were lower by 0.16 +/- 0.14 mg . min(-1) . cm(-2) (P < 0.01) and 191 +/- 122 g (P < 0.001), respectively, and SkBF tended to be lower (P = 0.06) by 5.4%maxAU +/- 13.4%maxAU in the ICE trial. Changes in Tre and Tsk were similar throughout exercise with ICE compared to 37 degrees C fluid ingestion. CONCLUSIONS: Relative to 37 degrees C, ICE ingestion caused disproportionately greater reductions in Esk relative to Hfluid, resulting in a lower HLnet and greater S. Mechanistically, LSR and possibly SkBF were suppressed independently of Tre or Tsk, reaffirming the concept of human abdominal thermoreception. From a heat balance perspective, recommendations for ICE ingestion during exercise in warm, dry conditions should be reconsidered. PMID- 26258858 TI - Biomechanical Deficit Profiles Associated with ACL Injury Risk in Female Athletes. AB - PURPOSE: This study aimed to quantify the prevalence of biomechanical deficit patterns associated with anterior cruciate ligament injury risk and their interconnections in a large cohort of female athletes during an unanticipated cutting task. METHODS: High school female athletes (n = 721) performed an unanticipated cutting task in the biomechanics laboratory. Trunk and lower extremity three-dimensional kinetics and kinematics were measured and entered into a latent profile analysis model. RESULTS: Approximately 40% of female athletes demonstrated no biomechanical deficits and were categorized into the low risk group. The second most prevalent profile (24%) demonstrated a combination of high quadriceps and leg dominance deficits and was labeled as quadriceps-leg. The third most prevalent profile (22%) demonstrated a combination of trunk and leg dominance deficits and to lesser extent ligament dominance deficits and was labeled as trunk-leg-ligament. Finally, the fourth profile (14%) demonstrated very high ligament dominance deficits only and it was labeled as ligament dominance profile. CONCLUSIONS: This is the first study to identify the most common biomechanical profiles associated with anterior cruciate ligament injury during a cutting task in a large cohort of female athletes. Approximately 60% of female athletes belong to one of the high-risk profiles. With the exception of the ligament dominance profile, the current analysis indicates that risk profiles consist of a combination of biomechanical deficits. The findings provide important insight into the prevalence of biomechanical deficits and future directions for the development of injury prevention programs. The findings can be used to guide the development of quick and easy tests that accurately categorize athletes into one of the profiles and subsequently prescribe tailored injury prevention programs that will be more effective and efficient than the current generic ones. PMID- 26258859 TI - Neurovascular Control and Cardiac Structure in Amateur Runners with Hypertension. AB - PURPOSE: The neurovascular mechanisms underlying hypertension are minimized by exercise training. However, it is not known whether previously trained individuals with hypertension would have deleterious repercussion of this disease. Our aim was to investigate the neurovascular control and the cardiac structure of athletes with hypertension. METHODS: Muscle sympathetic nerve activity (MSNA) (microneurography), baroreflex sensitivity (intravenous infusion of phenylephrine and nitroprusside), arterial stiffness (pulse wave velocity and echotracking), and cardiac structure (echocardiography) were evaluated in 17 runners with hypertension (42 +/- 1 yr) and 20 normotensive (43 +/- 1 yr) amateur runners. RESULTS: Runners with hypertension had higher MSNA (+24% burst frequency, P = 0.02; +24%, burst incidence, P < 0.01), left ventricular mass (+22%, P < 0.01), septum wall thickness (+9%, P = 0.04), posterior wall thickness (+11%, P = 0.04), and left atrium (+11%, P < 0.001) compared with normotensive runners. Baroreflex control of heart rate was lower in runners with hypertension during increase (P = 0.05) but not during decrease (P = 0.11) of systolic blood pressure when compared with normotensive runners. There was no difference between groups in baroreflex control of MSNA during increase (P = 0.38) and decrease (P = 0.36) of diastolic blood pressure. Pulse wave velocity (P = 0.71) and carotid variables: intima media thickness (P = 0.18), diameter (P = 0.09), and distension (P = 0.79) were similar between groups. CONCLUSIONS: Sympathetic overactivity seems to be involved in the underlying mechanisms of hypertension in amateur runners. Alterations in cardiac structure and decreased baroreflex control of heart rate suggest limited protection from exercise training. However, baroreflex control of MSNA and elastic properties of artery are preserved in this population. PMID- 26258860 TI - Adverse Cardiovascular Response to Aerobic Exercise Training: Is This a Concern? AB - PURPOSE: Aerobic exercise training in sedentary individuals improves physical fitness and various cardiovascular (CV) biomarkers. Nevertheless, there has been controversy as to whether exercise training may adversely affect some biomarkers in a small segment of the population. The purpose of this study was to investigate whether clinically significant worsening of CV biomarkers was more prevalent among individuals randomized to a supervised endurance training program as compared with those randomized to a control condition. METHODS: Baseline and end of study measurements of fasting insulin (FI), triglycerides (TG), resting systolic blood pressure (SBP), and HDL cholesterol (HDL-C) were obtained on 1188 healthy sedentary subjects from 4 clinical studies. Each study randomized subjects to 4- to 6-month supervised aerobic exercise programs or to a control group of no supervised exercise training. For each of the 4 CV biomarkers, we calculated the respective proportions of control and exercise group subjects whose baseline-to-follow-up changes were greater than or equal to previously reported adverse change (AC) thresholds. Those thresholds were increases of 24 pmol . L(-1) or greater for FI, 0.42 mmol . L(-1) or greater for TG, 10 mm Hg or greater for SBP, and a decrease of 0.12 mmol . L(-1) or greater for HDL-C. RESULTS: The respective proportions of subjects meeting the AC threshold in the control and exercise groups were 15.2% versus 9.6% (P = 0.02) for FI, 14.9% versus 13.1% (P = 0.37) for TG, 16.9% versus 15.8% (P = 0.52) for SBP, and 28.6% versus 22.5% (P = 0.03) for HDL-C. All were nonsignificant at the 0.0125 Bonferroni threshold adjusting for multiple comparisons. CONCLUSIONS: These findings do not support the concept that aerobic exercise training increases the risk of adverse changes in the CV biomarkers we studied. PMID- 26258861 TI - Intravenous Fibrinolytic Therapy in Central Retinal Artery Occlusion: A Patient Level Meta-analysis. AB - IMPORTANCE: Central retinal artery occlusion (CRAO) is an ophthalmologic emergency that can result in blindness. At present, no proven therapy for CRAO exists. Treatment with fibrinolytic agents has shown promise but remains of unproven benefit. OBJECTIVES: To assess the efficacy of systemic fibrinolytic therapy for patients with CRAO and to define a time window of efficacy. DATA SOURCES: We systematically queried PubMed, Web of Science, and Scopus using the following index terms: "retinal artery occlusion" OR "retinal ischemia" AND "thrombolysis" OR "fibrinolysis" OR "tissue plasminogen activator" OR "streptokinase" OR "urokinase." Search was not limited by year of publication or language and was conducted in August 2014. In addition, we evaluated the references from relevant review articles. STUDY SELECTION: We assembled observational studies reporting on visual acuity outcomes after CRAO. Inclusion criteria were complete reporting of visual outcomes after CRAO (with or without fibrinolytic therapy) and a series of more than 5 patients for fibrinolysis treatment or more than 20 cases when untreated or treated with conservative modalities. DATA EXTRACTION AND SYNTHESIS: Patient-level data were sought for studies reporting outcomes of treatment with fibrinolysis. Summary statistics were obtained for conservative treatment and natural history studies. The studies were weighted by the inverse of variance and merged in a random-effects model. MAIN OUTCOMES AND MEASURES: Rate of visual recovery (defined as improvement of visual acuity from 20/200 or worse at presentation to 20/100 or better) was calculated for patients treated with fibrinolytic and conservative therapies and those who received no treatment. RESULTS: We obtained summary statistics from 7 studies that included 396 patients who received no treatment after CRAO and from 8 studies that included 419 patients treated with ocular massage, anterior chamber paracentesis, and/or hemodilution (conservative treatment). Patient-level data were obtained for 147 patients treated with systemic fibrinolysis. We found that fibrinolysis was beneficial at 4.5 hours or earlier after symptom onset compared with the natural history group (17 of 34 [50.0%] vs 70 of 396 [17.7%]; odds ratio, 4.7 [95% CI, 2.3-9.6]; P < .001). Absolute risk reduction was 32.3%, with a number needed to treat of 4.0 (95% CI, 2.6-6.6). We also found that conservative treatment significantly worsened visual acuity outcomes and recovery rates after CRAO compared with the natural history group (31 of 419 [7.4%; 95% CI, 3.7%-11.1%] vs 70 of 396 [17.7%; 95% CI, 13.9%-21.4%]; P < .001; number needed to harm, 10.0 [95% CI, 6.8-17.4]). CONCLUSIONS AND RELEVANCE: Our analysis suggests that a clinical trial of early systemic fibrinolytic therapy for CRAO is warranted and that conservative treatments are futile and may be harmful. PMID- 26258862 TI - Changing incidence of cystic fibrosis in Wisconsin, USA. AB - RATIONALE: Previous investigations of cystic fibrosis (CF) incidence in Massachusetts, Colorado, and Minnesota (USA) yielded contradictory results, particularly regarding allele p.Phe508del; the racial compositions of the cohorts were not reported. OBJECTIVES: To clarify discrepancies in reported incidence with the ultimate goal of improving screening and quality of care, we assessed CF incidence, stratified by race and mutations in cystic fibrosis transmembrane conductance regulator (CFTR), in Wisconsin (USA) from 1994 to 2011. METHODS: Data on patients diagnosed with CF (N = 283), CFTR genotypes, CF carriers, and birth rate were collected. All data were categorized by racial background of the birth mother and the incidence of CF births was accordingly adjusted. Spearman's nonparametric rank correlation and Fisher's exact test were performed for continuous and categorical variables, respectively. Trends over time were fitted with a cubic spline. RESULTS: We detected a trending increase in CF cases (range within all data 1.67-2.98 per 10,000 births per year), homozygous p.Phe508del cases (0.57-1.79 per 10,000), heterozygous p.Phe508del cases (0.29-1.55 per 10,000), and cases lacking p.Phe508del (0-0.45 per 10,000). Both the number of cases lacking the p.Phe508del mutation per year and the number of cases lacking p.Phe508del per 10,000 births significantly increased (P = 0.05) from 1994 to 2011; the increase in overall incidence was not significant. The number of carriers identified through newborn screening significantly increased within the non-Hispanic Black (P = 0.0.021) and Hispanic (P = 0.003) populations. CONCLUSION: The racial composition of the CF cohort is changing in Wisconsin, possibly influencing disease detection, care, and outcome. PMID- 26258863 TI - Is there a link between exertional heat stroke and susceptibility to malignant hyperthermia? AB - OBJECTIVE: The identification of a predisposition toward malignant hyperthermia (MH) as a risk factor for exertional heat stroke (EHS) remains a matter of debate. Such a predisposition indicates a causal role for MH susceptibility (MHS) after EHS in certain national recommendations and has led to the use of an in vitro contracture test (IVCT) to identify the MHS trait in selected or unselected EHS patients. The aim of this study was to determine whether the MHS trait is associated with EHS. METHODS: EHS subjects in the French Armed Forces were routinely examined for MHS after experiencing an EHS episode. This retrospective study compared the features of IVCT-diagnosed MHS (iMHS) EHS subjects with those of MH-normal EHS patients and MH patients during the 2004-2010 period. MHS status was assessed using the European protocol. RESULTS: During the study period, 466 subjects (median age 25 years; 31 women) underwent MHS status investigation following an EHS episode. None of the subjects reported previous MH events. An IVCT was performed in 454 cases and was diagnostic of MHS in 45.6% of the study population, of MH susceptibility to halothane in 18.5%, of MH susceptibility to caffeine in 9.9%, and of MH susceptibility to halothane and caffeine in 17.2%. There were no differences in the clinical features, biological features or outcomes of iMHS EHS subjects compared with those of MH-normal or caffeine or halothane MHS subjects without known prior EHS episode. The recurrence rate was 12.7% and was not associated with MH status or any clinical or biological features. iMHS EHS patients exhibited a significantly less informative IVCT response than MH patients. CONCLUSIONS: The unexpected high prevalence of the MHS trait after EHS suggested a latent disturbance of calcium homeostasis that accounted for the positive IVCT results. This study did not determine whether EHS patients have an increased risk of MH, and it could not determine whether MH susceptibility is a risk factor for EHS. PMID- 26258864 TI - Association of the I264T variant in the sulfide quinone reductase-like (SQRDL) gene with osteoporosis in Korean postmenopausal women. AB - To identify novel susceptibility variants for osteoporosis in Korean postmenopausal women, we performed a genome-wide association analysis of 1180 nonsynonymous single nucleotide polymorphisms (nsSNPs) in 405 individuals with osteoporosis and 722 normal controls of the Korean Association Resource cohort. A logistic regression analysis revealed 72 nsSNPs that showed a significant association with osteoporosis (p<0.05). The top 10 nsSNPs showing the lowest p values (p = 5.2*10-4-8.5*10-3) were further studied to investigate their effects at the protein level. Based on the results of an in silico prediction of the protein's functional effect based on amino acid alterations and a sequence conservation evaluation of the amino acid residues at the positions of the nsSNPs among orthologues, we selected one nsSNP in the SQRDL gene (rs1044032, SQRDL I264T) as a meaningful genetic variant associated with postmenopausal osteoporosis. To assess whether the SQRDL I264T variant played a functional role in the pathogenesis of osteoporosis, we examined the in vitro effect of the nsSNP on bone remodeling. Overexpression of the SQRDL I264T variant in the preosteoblast MC3T3-E1 cells significantly increased alkaline phosphatase activity, mineralization, and the mRNA expression of osteoblastogenesis markers, Runx2, Sp7, and Bglap genes, whereas the SQRDL wild type had no effect or a negative effect on osteoblast differentiation. Overexpression of the SQRDL I264T variant did not affect osteoclast differentiation of the primary-cultured monocytes. The known effects of hydrogen sulfide (H2S) on bone remodeling may explain the findings of the current study, which demonstrated the functional role of the H2S-catalyzing enzyme SQRDL I264T variant in osteoblast differentiation. In conclusion, the results of the statistical and experimental analyses indicate that the SQRDL I264T nsSNP may be a significant susceptibility variant for osteoporosis in Korean postmenopausal women that is involved in osteoblast differentiation. PMID- 26258866 TI - Does High Alveolar Fluid Reabsorption Prevent HAPE in Individuals with Exaggerated Pulmonary Hypertension in Hypoxia? AB - An exaggerated increase in pulmonary arterial systolic pressure (PAsP) is a highlight of high altitude pulmonary edema (HAPE). However, the incidence of HAPE at 4559 m was much lower in altitude-naive individuals with exaggerated pulmonary vasoconstriction (HPV) in normobaric hypoxia than in known HAPE-susceptibles, indicating that elevated PAsP alone is insufficient to induce HAPE. A decreased nasal potential difference (NPD) has been found in HAPE-susceptibles, where, based on animal models, NPD serves as surrogate of alveolar epithelial ion transport. We hypothesize that those HAPE-resistant individuals with high HPV may be protected by elevated alveolar Na and fluid reabsorption, which might be detected as increased NPD. To test this hypothesis, we measured NPD in normoxia of subjects who were phenotyped in previous studies as high altitude tolerant (controls), known HAPE-susceptibles with high HPV (HP+HAPE), as well as individuals with high HPV but without HAPE (HP-no-HAPE) at 4559 m. NPD and amiloride-sensitive NPD were lower in HP+HAPE than in controls, whereas HP-no HAPE were not different from either group. There were no differences in Cl transport between groups. Our results show low nasal ion transport in HAPE but higher transport in those individuals with the highest HPV but without HAPE. This indicates that in some individuals with high PAsP at high altitude high alveolar fluid reabsorption might protect them from HAPE. PMID- 26258868 TI - Religion, spirituality, and physical health in cancer patients: A meta-analysis. AB - Although religion/spirituality (R/S) is important in its own right for many cancer patients, a large body of research has examined whether R/S is also associated with better physical health outcomes. This literature has been characterized by heterogeneity in sample composition, measures of R/S, and measures of physical health. In an effort to synthesize previous findings, a meta analysis of the relation between R/S and patient-reported physical health in cancer patients was performed. A search of PubMed, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library yielded 2073 abstracts, which were independently evaluated by pairs of raters. The meta analysis was conducted for 497 effect sizes from 101 unique samples encompassing more than 32,000 adult cancer patients. R/S measures were categorized into affective, behavioral, cognitive, and 'other' dimensions. Physical health measures were categorized into physical well-being, functional well-being, and physical symptoms. Average estimated correlations (Fisher z scores) were calculated with generalized estimating equations with robust variance estimation. Overall R/S was associated with overall physical health (z = 0.153, P < .001); this relation was not moderated by sociodemographic or clinical variables. Affective R/S was associated with physical well-being (z = 0.167, P < .001), functional well-being (z = 0.343, P < .001), and physical symptoms (z = 0.282, P < .001). Cognitive R/S was associated with physical well-being (z = 0.079, P < .05) and functional well-being (z = 0.090, P < .01). 'Other' R/S was associated with functional well-being (z = 0.100, P < .05). In conclusion, the results of the current meta-analysis suggest that greater R/S is associated with better patient-reported physical health. These results underscore the importance of attending to patients' religious and spiritual needs as part of comprehensive cancer care. PMID- 26258871 TI - Polyfuran-Derived Microporous Carbons for Enhanced Adsorption of CO2 and CH4. AB - Oxygen-doped microporous carbons were synthesized by chemical activation of polyfuran with KOH or ZnCl2 at 600 and 800 degrees C. It was found that KOH preserves and ZnCl2 eliminates the O-C functional groups in the activation process. The O-doped carbon activated with KOH at 800 degrees C exhibited a high CO2 capacity (4.96 mmol g(-1), 273 K, 1 bar) and CH4 adsorption capacity (2.27 mmol g(-1), 273 K, 1 bar). At 298 K and 1 bar, a very high selectivity for separating CO2/N2 (41.7) and CO2/CH4 (6.8) gas mixture pairs was obtained on the O-doped carbon activated with KOH at 600 degrees C. The excellent separation ability of the O-doped carbons was demonstrated in transient breakthrough simulations of CO2/CH4/N2 mixtures in a fixed bed adsorber. The isosteric adsorption heats of the O-doped carbons were also significantly lower than those of MOF-74 and NaX zeolite. The O-doped microporous carbon adsorbents appear to be a very promising adsorbent for CO2 capture from flue gas, biogas upgrading, and CH4 storage. PMID- 26258870 TI - Depression and Posttraumatic Stress Symptoms After Perinatal Loss in a Population Based Sample. AB - INTRODUCTION: Perinatal loss is often a traumatic outcome for families. While there are limited data about depressive outcomes in small populations, information about depression and posttraumatic stress disorder among large racially and economically diverse populations is sparse. METHODS: We collaborated with the Michigan Department of Community Health to conduct a longitudinal survey of bereaved mothers with stillbirth or infant death under 28 days of life and live-birth (control) mothers in Michigan. The study assessed 9-month mental health outcomes including self-reported symptoms of depression and posttraumatic stress disorder along with information about demographics, pregnancy and loss experience, social support, and past and present mental health and treatment. RESULTS: Of 1400 women contacted by the State of Michigan, 609 completed surveys and were eligible to participate for a 44% response rate (377 bereaved mothers and 232 control mothers with live births). In multivariable analysis, bereaved women had nearly 4-fold higher odds of having a positive screen for depression and 7-fold higher odds of a positive screen for post-traumatic stress disorder after controlling for demographic and personal risk variables. A minority of screen-positive women were receiving any type of psychiatric treatment. CONCLUSION: This is the largest epidemiologically based study to date to measure the psychological impact of perinatal loss. Nine months after a loss, bereaved women showed high levels of distress with limited rates of treatment. Symptoms need to be monitored over time for persisting disorder and further research should identify women at highest risk for poor outcomes. PMID- 26258869 TI - Metagenomic Analysis of Antibiotic Resistance Genes in Dairy Cow Feces following Therapeutic Administration of Third Generation Cephalosporin. AB - Although dairy manure is widely applied to land, it is relatively understudied compared to other livestock as a potential source of antibiotic resistance genes (ARGs) to the environment and ultimately to human pathogens. Ceftiofur, the most widely used antibiotic used in U.S. dairy cows, is a 3rd generation cephalosporin, a critically important class of antibiotics to human health. The objective of this study was to evaluate the effect of typical ceftiofur antibiotic treatment on the prevalence of ARGs in the fecal microbiome of dairy cows using a metagenomics approach. beta-lactam ARGs were found to be elevated in feces from Holstein cows administered ceftiofur (n = 3) relative to control cows (n = 3). However, total numbers of ARGs across all classes were not measurably affected by ceftiofur treatment, likely because of dominance of unaffected tetracycline ARGs in the metagenomics libraries. Functional analysis via MG-RAST further revealed that ceftiofur treatment resulted in increases in gene sequences associated with "phages, prophages, transposable elements, and plasmids", suggesting that this treatment also enriched the ability to horizontally transfer ARGs. Additional functional shifts were noted with ceftiofur treatment (e.g., increase in genes associated with stress, chemotaxis, and resistance to toxic compounds; decrease in genes associated with metabolism of aromatic compounds and cell division and cell cycle), along with measureable taxonomic shifts (increase in Bacterioidia and decrease in Actinobacteria). This study demonstrates that ceftiofur has a broad, measureable and immediate effect on the cow fecal metagenome. Given the importance of 3rd generation cephalospirins to human medicine, their continued use in dairy cattle should be carefully considered and waste treatment strategies to slow ARG dissemination from dairy cattle manure should be explored. PMID- 26258872 TI - Electrospun Nanofibrous P(DLLA-CL) Balloons as Calcium Phosphate Cement Filled Containers for Bone Repair: in Vitro and in Vivo Studies. AB - The spinal surgeon community has expressed significant interest in applying calcium phosphate cement (CPC) for the treatment of vertebral compression fractures (VCFs) and minimizing its disadvantages, such as its water-induced collapsibility and poor mechanical properties, limiting its clinical use. In this work, novel biodegradable electrospun nanofibrous poly(d,l-lactic acid-epsilon caprolactone) balloons (ENPBs) were prepared, and the separation, pressure, degradation, and new bone formation behaviors of the ENPBs when used as CPC filled containers in vitro and in vivo were systematically analyzed and compared. CPC could be separated from surrounding bone tissues by ENPBs in vitro and in vivo. ENPB-CPCs (ENPBs serving as CPC-filled containers) exerted pressure on the surrounding bone microenvironment, which was enough to crush trabecular bone. Compared with the CPC implantation, ENPB-CPCs delayed the degradation of CPC (i.e., its water-induced collapsilibity). Finally, possible mechanisms behind the in vivo effects caused by ENPB-CPCs implanted into rabbit thighbones and pig vertebrae were proposed. This work suggests that ENPBs can be potentially applied as CPC-filled containers in vivo and provides an experimental basis for the clinical application of ENPBs for the treatment of VCFs. In addition, this work will be of benefit to the development of polymer-based medical implants in the future. PMID- 26258867 TI - Recent Developments in Magnetic Diagnostic Systems. PMID- 26258873 TI - Exceptional Association of Syringotropic Mycosis Fungoides with Chronic Lymphocytic Leukaemia. PMID- 26258874 TI - Interventions for preventing and treating kidney disease in Henoch-Schonlein Purpura (HSP). AB - BACKGROUND: Henoch-Schonlein purpura (HSP) is the most common vasculitis of childhood but may occur in adults. This small vessel vasculitis is characterised by palpable purpura, abdominal pain, arthritis or arthralgia and kidney involvement. This is an update of a review first published in 2009. OBJECTIVES: To evaluate the benefits and harms of different agents (used singularly or in combination) compared with placebo, no treatment or any other agent for: (1) the prevention of severe kidney disease in patients with HSP without kidney disease at presentation; (2) the prevention of severe kidney disease in patients with HSP and minor kidney disease (microscopic haematuria, mild proteinuria) at presentation; (3) the treatment of established severe kidney disease (macroscopic haematuria, proteinuria, nephritic syndrome, nephrotic syndrome with or without acute kidney failure) in HSP; and (4) the prevention of recurrent episodes of HSP associated kidney disease. SEARCH METHODS: We searched the Cochrane Kidney and Transplant's Specialised Register to 13 July 2015 through contact with the Trials Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing interventions used to prevent or treat kidney disease in HSP compared with placebo, no treatment or other agents were included. DATA COLLECTION AND ANALYSIS: Two authors independently determined study eligibility, assessed risk of bias and extracted data from each study. Statistical analyses were performed using the random effects model and the results were expressed as risk ratio (RR) or risk difference (RD) for dichotomous outcomes and mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). MAIN RESULTS: Thirteen studies (1403 enrolled patients) were identified. Risks of bias attributes were frequently poorly performed. Low risk of bias was reported in six studies (50%) for sequence generation (selection bias) and in seven (58%) for allocation concealment (selection bias). Blinding of participants and personnel (performance bias) and of outcome assessment (detection bias) was at low risk of bias in three studies. Five studies reported complete outcome data (attrition bias) while eight studies reported expected outcomes so were at low risk of reporting bias.Eight studies evaluated therapy to prevent persistent kidney disease in HSP. There was no significant difference in the risk of persistent kidney disease any time after treatment (5 studies, 746 children: RR 0.74, 95% CI 0.42 to 1.32), or at one, three, six and 12 months in children given prednisone for 14 to 28 days at presentation of HSP compared with placebo or supportive treatment. There were no significant differences in the risk of persistent kidney disease with antiplatelet therapy in children with or without kidney disease at entry. Heparin significantly reduced the risk of persistent kidney disease by three months compared with placebo (1 study, 228 children: RR 0.27, 95% CI 0.14 to 0.55); no significant bleeding occurred. Four studies examined the treatment of severe HSP associated kidney disease. Two studies (one involving 56 children and the other involving 54 adults) compared cyclophosphamide with placebo or supportive treatment and found no significant benefit of cyclophosphamide. There were no significant differences in adverse effects. In one study comparing cyclosporin with methylprednisolone (15 children) there was no significant difference in remission at final follow-up at a mean of 6.3 years (RR 1.37, 95% CI 0.74 to 2.54). In one study (17 children) comparing mycophenolate mofetil with azathioprine, there was no significant difference in the remission of proteinuria at one year (RR 1.32, 95% CI 0.86 to 2.03). No studies were identified which evaluated the efficacy of therapy on kidney disease in participants with recurrent episodes of HSP. AUTHORS' CONCLUSIONS: There are no substantial changes in conclusions from this update compared with the initial review. From generally low quality evidence, we found no evidence of benefit from RCTs for the use of prednisone or antiplatelet agents to prevent persistent kidney disease in children with HSP. Though heparin appeared effective, this potentially dangerous therapy is not justified to prevent serious kidney disease when fewer than 2% of children with HSP develop severe kidney disease. No evidence of benefit has been found for cyclophosphamide treatment in children or adults with HSP and severe kidney disease. Because of small patient numbers and events leading to imprecision in results, it remains unclear whether cyclosporin and mycophenolate mofetil have any roles in the treatment of children with HSP and severe kidney disease. PMID- 26258875 TI - FV-429 induces apoptosis and inhibits glycolysis by inhibiting Akt-mediated phosphorylation of hexokinase II in MDA-MB-231 cells. AB - In this study, the anticancer effect of a newly synthesized flavonoid FV-429, against human breast cancer MDA-MB-231 cells, and the underlying mechanisms were investigated. FV-429 triggered the apoptosis and simultaneously inhibited the glycolysis of MDA-MB-231 cells. Both the HK II activity and its level in mitochondria were significantly down regulated by FV-429. Moreover, FV-429 weakened the interaction between HKII and VDAC, stimulated the detachment of HK II from the mitochondria, and resulted in the opening of the mitochondrial permeability transition pores. Thus FV-429 induced the mitochondrial-mediated apoptosis, showing increased Bax/Bcl-2 ratio, loss of mitochondrial membrane potential (MMP) and activation of caspase-3 and -9, cytochrome c (Cyt c) release, and apoptosis inducing factor (AIF) transposition. Further research revealed that the phosphorylation of mitochondrial HKII via Akt was responsible for the dissociation of HKII and the decreased HKII activity induced by FV-429. Taken together, FV-429 inhibited the phosphorylation of HKII, down-regulated its activity, and stimulated the release of HKII from the mitochondria, resulting the inhibited glycolysis and mitochondrial-mediated apoptosis. The studies provide a molecular basis for the development of flavonoid compounds as novel anticancer agents for breast cancer. (c) 2015 Wiley Periodicals, Inc. PMID- 26258876 TI - Selective electrochemical sensing of human serum albumin by semi-covalent molecular imprinting. AB - We devised and prepared a conducting molecularly imprinted polymer (MIP) for human serum albumin (HSA) determination using semi-covalent imprinting. The bis(2,2'-bithien-5-yl)methane units constituted the MIP backbone. This MIP was deposited as a thin film on an Au electrode by oxidative potentiodynamic electropolymerization to fabricate an electrochemical chemosensor. The HSA template imprinting, and then its releasing from the MIP was confirmed by the differential pulse voltammetry (DPV), electrochemical impedance spectroscopy (EIS), XPS, and PM-IRRAS measurements as well as by AFM imaging. Semi-covalent imprinting provided a very well defined locations of recognition sites in the MIP molecular cavities. These sites populated the imprinted cavities or the MIP surface only. The DPV and EIS response of the MIP film coated electrode to the HSA analyte was linear in the range of 0.8 to 20 and 4 to 80 ug/mL HSA, respectively, with the limit of detection of 16.6 and 800 ng/mL, respectively. The impressively high imprinting factor reached, exceeding 20, strongly confirmed that semi-covalent imprinting resulted in formation of a large number of very well defined molecular cavities with high affinity to the HSA molecules. The MIP selectivity against low-(molecular weight) interferences, common for physiological fluids, such as blood and urea, was very high. There was no response to the presence of these interferences at concentrations encountered in the samples analyzed. Moreover, the chemosensor selectivity to the myoglobin and cytochrome c interferences was excellent while that to lysozyme was slightly lower but still high. The chemosensor was useful for determination of abnormal HSA concentration in a control blood serum. PMID- 26258877 TI - Constructing heterostructure on highly roughened caterpillar-like gold nanotubes with cuprous oxide grains for ultrasensitive and stable nonenzymatic glucose sensor. AB - In this study, a metal-metal oxide heterostructure was designed and constructed by growing cuprous oxide (Cu2O) grains on highly surface roughened caterpillar like Au nanotubes (CLGNs) for ultrasensitive, selective and stable nonenzymatic glucose biosensors. The Cu2O grains are tightly anchored to the surface of CLGNs by the spines, resulting in a large increase in the contact area between Cu2O grains and the CLGNs, which facilitates the electron transport between metal and metal oxide and improves the sensitivity and stability of the sensors. The electron transfer coefficient (alpha) and electron transfer rate constant (ks) for redox reaction of Cu2O-CLGNs/GCE are found to be 0.50114 and 3.24+/-0.1 s( 1), respectively. The biosensor shows a linear response to glucose over a concentration range of 0.1-5mM and a high sensitivity of 1215.7 uA mM(-1) cm(-2) with a detection limit of 1.83 MUM. Furthermore, the Cu2O-CLGNs biosensor exhibited strong anti-interference capability against uric acid (UA), ascorbic acid (AA), potassium chloride (KCl) and sodium ascorbate (SA), as well as a high stability and repeatability. Our current research indicates that the Cu2O-CLGNs hybrid electrode is a promising choice for constructing nonenzyme based electrochemical biosensors. PMID- 26258878 TI - Primary Cutaneous T-cell Lymphoma With Coexpression of T-Cell Receptors alphabeta and gammadelta. AB - T lymphocytes belong to 2 distinct sublineages that express either alphabeta or gammadelta T-cell receptor (TCR) complex. Although malignancy is a great instigator of lineage infidelity, as exemplified by aberrant expression of numerous lineage markers in lymphoma cells, malignant T cells rarely coexpress alphabeta and gammadelta TCR complexes. Similarly, only rare cases of CD4/CD8 double-positive primary cutaneous T-cell lymphoma have been reported. In this report, we describe a remarkable case of primary cutaneous T-cell lymphoma coexpressing alphabeta and gammadelta TCR complexes, strong diffuse CD8, and a very restricted coexpression of CD4 and CD8. A 66-year-old man was referred to our center for treatment of a persistent eczematoid eruption of 6 years of duration. An initial biopsy demonstrated not only marked spongiosis, but also an epidermotropic population of CD4 small mature T cells with partial expression of CD8. The process remained indolent for another year, followed by an abrupt progression with development of plaques and tumors. Repeat biopsies of these lesions demonstrated a superimposed population of large anaplastic T cells extensively involving the dermis and epidermis. The large cells showed a strong uniform expression of CD3, CD8, CD45RA, CD5, granzyme, TIA1, perforin, TCR-beta, and TCR-gamma and a weaker but unambiguous expression of CD4, CD25, CD2, and CD56. TCR gene rearrangement studies showed clonal rearrangements for TCR-beta and TCR-gamma with identical peaks to those seen in the biopsy from a year earlier. The patient developed lymphadenopathy, with a biopsy showing nodal involvement by a morphologically and phenotypically identical neoplastic T-cell population. The disease showed partial response to systemic chemotherapy with development of new plaques, but these new lesions have regressed with radiation therapy. PMID- 26258879 TI - Antigen presentation kinetics control T cell/dendritic cell interactions and follicular helper T cell generation in vivo. AB - The production of high affinity, class switched antibodies produced by B cells hinges on the effective differentiation of T follicular helper (Tfh) cells. Here we define conditions specifically enhancing Tfh differentiation and providing protection in a model of influenza infection. Tfh responses were associated with prolonged antigen presentation by dendritic cells (DCs), which maintained T cell/DC interactions into stage 3 (>72 hr) of activation. Blocking stage 3 interactions ablated Tfh generation, demonstrating a causal link between T cell DC behaviour and functional outcomes. The current data therefore explain how duration of antigen presentation affects the dynamics of T cell-DC interactions and consequently determine Tfh cell differentiation in the developing immune response. PMID- 26258880 TI - Structural basis for recognition and remodeling of the TBP:DNA:NC2 complex by Mot1. AB - Swi2/Snf2 ATPases remodel substrates such as nucleosomes and transcription complexes to control a wide range of DNA-associated processes, but detailed structural information on the ATP-dependent remodeling reactions is largely absent. The single subunit remodeler Mot1 (modifier of transcription 1) dissociates TATA box-binding protein (TBP):DNA complexes, offering a useful system to address the structural mechanisms of Swi2/Snf2 ATPases. Here, we report the crystal structure of the N-terminal domain of Mot1 in complex with TBP, DNA, and the transcription regulator negative cofactor 2 (NC2). Our data show that Mot1 reduces DNA:NC2 interactions and unbends DNA as compared to the TBP:DNA:NC2 state, suggesting that Mot1 primes TBP:NC2 displacement in an ATP-independent manner. Electron microscopy and cross-linking data suggest that the Swi2/Snf2 domain of Mot1 associates with the upstream DNA and the histone fold of NC2, thereby revealing parallels to some nucleosome remodelers. This study provides a structural framework for how a Swi2/Snf2 ATPase interacts with its substrate DNA:protein complex. PMID- 26258881 TI - The HIV-1 envelope protein gp120 is captured and displayed for B cell recognition by SIGN-R1(+) lymph node macrophages. AB - The HIV-1 envelope protein gp120 is both the target of neutralizing antibodies and a major focus of vaccine efforts; however how it is delivered to B cells to elicit an antibody response is unknown. Here, we show that following local gp120 injection lymph node (LN) SIGN-R1(+) sinus macrophages located in interfollicular pockets and underlying SIGN-R1(+) macrophages form a cellular network that rapidly captures gp120 from the afferent lymph. In contrast, two other antigens, phycoerythrin and hen egg lysozyme, were not captured by these cells. Intravital imaging of mouse LNs revealed persistent, but transient interactions between gp120 bearing interfollicular network cells and both trafficking and LN follicle resident gp120 specific B cells. The gp120 specific, but not the control B cells repetitively extracted gp120 from the network cells. Our findings reveal a specialized LN antigen delivery system poised to deliver gp120 and likely other pathogen derived glycoproteins to B cells. PMID- 26258882 TI - The activation of IgM- or isotype-switched IgG- and IgE-BCR exhibits distinct mechanical force sensitivity and threshold. AB - B lymphocytes use B cell receptors (BCRs) to sense the physical features of the antigens. However, the sensitivity and threshold for the activation of BCRs resulting from the stimulation by mechanical forces are unknown. Here, we addressed this question using a double-stranded DNA-based tension gauge tether system serving as a predefined mechanical force gauge ranging from 12 to 56 pN. We observed that IgM-BCR activation is dependent on mechanical forces and exhibits a multi-threshold effect. In contrast, the activation of isotype switched IgG- or IgE-BCR only requires a low threshold of less than 12 pN, providing an explanation for their rapid activation in response to antigen stimulation. Mechanistically, we found that the cytoplasmic tail of the IgG-BCR heavy chain is both required and sufficient to account for the low mechanical force threshold. These results defined the mechanical force sensitivity and threshold that are required to activate different isotyped BCRs. PMID- 26258883 TI - CD73 Activity is Dispensable for the Polarization of M2 Macrophages. AB - The ectoenzyme CD73 catalyzes the hydrolysis of AMP, and is one of the most important producers of extracellular adenosine. On regulatory T cells, CD73 is necessary for immunosuppressive functions, and on Th17 cells CD73-generated adenosine exerts anti-inflammatory effects. However, the expression and function of CD73 in pro-inflammatory M1 and in immunosuppressive M2 macrophages is largely unknown. Here we show that CD73 expression and enzyme activity were induced in in vitro polarized pro-inflammatory human M(LPS+TNF) monocytes/macrophages, while CD73 was absent from immunosuppressive M(IL-4+M-CSF)-polarized macrophages. Inhibition of CD73 activity with the inhibitor AMPCP did not affect the polarization of human monocytes. In mice, CD73 was present on resident peritoneal macrophages. In striking contrast, elicited peritoneal macrophages remained CD73 negative regardless of their polarization towards either a pro-inflammatory M(LPS) or anti-inflammatory M(IL-4c) direction. Finally, the ability of peritoneal macrophages to polarize to pro- and anti-inflammatory cells was perfectly normal in CD73-deficient mice in vivo. These data indicate that, in contrast to other major leukocyte subpopulations, CD73 activity on macrophages does not play a major role in their polarization and that in mice host CD73 on any cell type is not required in vivo for peritoneal macrophage polarization towards either a pro- or an anti-inflammatory direction. PMID- 26258884 TI - Enantioselective Synthesis of (-)-Dysiherbaine. AB - Dysiherbaine, a natural product isolated from the Marine sponge Dysidea herbacea, has been shown to be a selective agonist of non-NMDA type glutamate receptors, kainate receptors. An enantioselective synthesis of dysiherbaine is reported. Metathesis of the diene followed by conversion of the resulting alkene to the amino alcohol and addition of the amino acid provides the natural product. This synthesis differs from previous approaches to the molecule in that the functionality on the tetrahydropyran ring is installed late in the route. PMID- 26258885 TI - Near-IR Two-Photon Fluorescent Sensor for K(+) Imaging in Live Cells. AB - A new two-photon excited fluorescent K(+) sensor is reported. The sensor comprises three moieties, a highly selective K(+) chelator as the K(+) recognition unit, a boron-dipyrromethene (BODIPY) derivative modified with phenylethynyl groups as the fluorophore, and two polyethylene glycol chains to afford water solubility. The sensor displays very high selectivity (>52-fold) in detecting K(+) over other physiological metal cations. Upon binding K(+), the sensor switches from nonfluorescent to highly fluorescent, emitting red to near IR (NIR) fluorescence. The sensor exhibited a good two-photon absorption cross section, 500 GM at 940 nm. Moreover, it is not sensitive to pH in the physiological pH range. Time-dependent cell imaging studies via both one- and two photon fluorescence microscopy demonstrate that the sensor is suitable for dynamic K(+) sensing in living cells. PMID- 26258886 TI - Theory and X-ray Absorption Spectroscopy for Aluminum Coordination Complexes - Al K-Edge Studies of Charge and Bonding in (BDI)Al, (BDI)AlR2, and (BDI)AlX2 Complexes. AB - Polarized aluminum K-edge X-ray absorption near edge structure (XANES) spectroscopy and first-principles calculations were used to probe electronic structure in a series of (BDI)Al, (BDI)AlX2, and (BDI)AlR2 coordination compounds (X = F, Cl, I; R = H, Me; BDI = 2,6-diisopropylphenyl-beta-diketiminate). Spectral interpretations were guided by examination of the calculated transition energies and polarization-dependent oscillator strengths, which agreed well with the XANES spectroscopy measurements. Pre-edge features were assigned to transitions associated with the Al 3p orbitals involved in metal-ligand bonding. Qualitative trends in Al 1s core energy and valence orbital occupation were established through a systematic comparison of excited states derived from Al 3p orbitals with similar symmetries in a molecular orbital framework. These trends suggested that the higher transition energies observed for (BDI)AlX2 systems with more electronegative X(1-) ligands could be ascribed to a decrease in electron density around the aluminum atom, which causes an increase in the attractive potential of the Al nucleus and concomitant increase in the binding energy of the Al 1s core orbitals. For (BDI)Al and (BDI)AlH2 the experimental Al K-edge XANES spectra and spectra calculated using the eXcited electron and Core-Hole (XCH) approach had nearly identical energies for transitions to final state orbitals of similar composition and symmetry. These results implied that the charge distributions about the aluminum atoms in (BDI)Al and (BDI)AlH2 are similar relative to the (BDI)AlX2 and (BDI)AlMe2 compounds, despite having different formal oxidation states of +1 and +3, respectively. However, (BDI)Al was unique in that it exhibited a low-energy feature that was attributed to transitions into a low-lying p-orbital of b1 symmetry that is localized on Al and orthogonal to the (BDI)Al plane. The presence of this low-energy unoccupied molecular orbital on electron-rich (BDI)Al distinguishes its valence electronic structure from that of the formally trivalent compounds (BDI)AlX2 and (BDI)AlR2. The work shows that Al K-edge XANES spectroscopy can be used to provide valuable insight into electronic structure and reactivity relationships for main-group coordination compounds. PMID- 26258888 TI - The manufacturing process should remain the focus for severe febrile reactions in children administered an Australian inactivated influenza vaccine during 2010. AB - Influenza vaccine safety is an ongoing issue. In 2010, inactivated trivalent influenza vaccines (TIVs), Fluvax((r)) and Fluvax Junior((r)) manufactured by CSL Biotherapies ('CSL'), Parkville, Australia, were associated with a marked increase in febrile seizures (FS) in children <5 years old. Extensive investigations initially failed to identify a root cause. The company's researchers recently published two papers outlining their latest findings. Cytokine responses to TIV were measured in paediatric whole blood assays (WBA); NF-kappaB activation was assessed using a HEK293 cell line reporter assay. CSL suggest that the combination of new influenza strains (H1N1 A/California/7/2009 and B/Brisbane/60/2008), increased complexes of viral RNA and lipid in the vaccine, and inherent sensitivities of some children <5 years old caused elevated inflammatory responses resulting in FS. Whilst the papers provide insight into pathogenesis, much remains unclear. The WBA were from only 10 'healthy' children, potentially affecting generalisability of the results and reliability of these in vitro tests in assessing future influenza vaccine safety. Increased fever rates (without FS) found in CSL TIV studies between 2005 and 2010 suggest a long standing contribution to reactogenicity from the manufacturing process. More detailed comparisons with non-CSL vaccines would have helped elucidate the relative contribution of patient/strain factors and the manufacturing process. The focus remains on manufacturing process differences as the key causative factor of elevated febrile responses. Studies underway, of modified vaccines in young children, will determine whether reactogenicity issues have been successfully addressed and whether CSL TIV can be relicensed in children <5 years of age. PMID- 26258887 TI - PARP14 promotes the Warburg effect in hepatocellular carcinoma by inhibiting JNK1 dependent PKM2 phosphorylation and activation. AB - Most tumour cells use aerobic glycolysis (the Warburg effect) to support anabolic growth and evade apoptosis. Intriguingly, the molecular mechanisms that link the Warburg effect with the suppression of apoptosis are not well understood. In this study, using loss-of-function studies in vitro and in vivo, we show that the anti apoptotic protein poly(ADP-ribose) polymerase (PARP)14 promotes aerobic glycolysis in human hepatocellular carcinoma (HCC) by maintaining low activity of the pyruvate kinase M2 isoform (PKM2), a key regulator of the Warburg effect. Notably, PARP14 is highly expressed in HCC primary tumours and associated with poor patient prognosis. Mechanistically, PARP14 inhibits the pro-apoptotic kinase JNK1, which results in the activation of PKM2 through phosphorylation of Thr365. Moreover, targeting PARP14 enhances the sensitization of HCC cells to anti-HCC agents. Our findings indicate that the PARP14-JNK1-PKM2 regulatory axis is an important determinant for the Warburg effect in tumour cells and provide a mechanistic link between apoptosis and metabolism. PMID- 26258890 TI - A paradigm shift in the treatment of central sleep apnea in heart failure. PMID- 26258892 TI - Microwave and Quantum Chemical Study of the Hydrazino Group as Proton Donor in Intramolecular Hydrogen Bonding of (2-Fluoroethyl)hydrazine (FCH2CH2NHNH2). AB - The microwave spectrum of (2-fluoroethyl)hydrazine (FCH2CH2NHNH2) was studied in the 11-123 GHz spectral region to investigate the ability of the hydrazino group to form intramolecular hydrogen bonds acting as a proton donor. This group can participate both in five-member and in six-member internal hydrogen bonds with the fluorine atom. The spectra of four conformers were assigned, and the rotational and centrifugal distortion constants of these rotameric forms were determined. Two of these conformers have five-member intramolecular hydrogen bonds, while the two other forms are without this interaction. The internal hydrogen bonds in the two hydrogen-bonded forms are assumed to be mainly electrostatic in origin because the N-H and C-F bonds are nearly parallel and the associated bond moments are antiparallel. This is the first example of a gas phase study of a hydrazine where the hydrazino functional group acts as a proton donor in weak intramolecular hydrogen bonds. Extensive quantum chemical calculations at the B3LYP/cc-pVTZ, MP2/cc-pVTZ, and CCSD/cc-pVQZ levels of theory accompanied and guided the experimental work. These calculations predict the existence of no less than 18 conformers, spanning a CCSD internal energy range of 15.4 kJ/mol. Intramolecular hydrogen bonds are predicted to be present in seven of these conformers. Three of these forms have six-member hydrogen bonds, while four have five-member hydrogen bonds. The three lowest-energy conformers have five-member internal hydrogen bonds. The spectrum of the conformer with the lowest energy was not assigned because it has a very small dipole moment. The CCSD relative energies of the two hydrogen-bonded rotamers whose spectra were assigned are 1.04 and 1.62 kJ/mol, respectively, whereas the relative energies of the two conformers with assigned spectra and no hydrogen bonds have relative energies of 6.46 and 4.89 kJ/mol. PMID- 26258891 TI - SPINK1 promotes colorectal cancer progression by downregulating Metallothioneins expression. AB - Colorectal cancer (CRC) is the third most common cancer in the world, and second leading cause of cancer deaths in the US. Although, anti-EGFR therapy is commonly prescribed for CRC, patients harboring mutations in KRAS or BRAF show poor treatment response, indicating an ardent demand for new therapeutic targets discovery. SPINK1 (serine peptidase inhibitor, Kazal type 1) overexpression has been identified in many cancers including the colon, lung, breast and prostate. Our study demonstrates the functional significance of SPINK1 in CRC progression and metastases. Stable knockdown of SPINK1 significantly decreases cell proliferation, invasion and soft agar colony formation in the colon adenocarcinoma WiDr cells. Conversely, an increase in these oncogenic phenotypes was observed on stimulation with SPINK1-enriched conditioned media (CM) in multiple benign models such as murine colonic epithelial cell lines, MSIE and YAMC (SPINK3-negative). Mechanistically, SPINK1 promotes tumorigenic phenotype by activating phosphatidylinositol 3-kinase (PI3K/AKT) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathways, and the SPINK1-positive WiDr cells are sensitive to AKT and MEK inhibitors. Importantly, SPINK1 silencing mediated upregulation of various Metallothionein isoforms, considered as tumor suppressors in CRC, confer sensitivity to doxorubicin, which strengthens the rationale for using the combinatorial treatment approach for the SPINK1-positive CRC patients. Furthermore, in vivo studies using chicken chorioallantoic membrane assay, murine xenograft studies and metastasis models further suggest a pivotal role of SPINK1 in CRC progression and metastasis. Taken together, our study demonstrates an important role for the overexpressed SPINK1 in CRC disease progression, a phenomenon that needs careful evaluation towards effective therapeutic target development. PMID- 26258893 TI - HisTOOLogy: an open-source tool for quantitative analysis of histological sections. AB - HisTOOLogy is an open-source software for the quantification of digital colour images of histological sections. The simple graphical user interface enables both expert and non-expert users to rapidly extract useful information from stained tissue sections. The software's main feature is a generalizable colour separation algorithm based on k-means clustering which accurately and reproducibly returns the amount of colour per unit area for any stain, thus allowing the quantification of tissue components. Here we describe HisTOOLogy's algorithms and graphical user interface structure, showing how it can be used to separate different dye colours in several classical stains. In addition, to demonstrate how the tool can be employed to obtain quantitative information on biological tissues, the effect of different hepatic tissue decellularization protocols on cell removal and matrix preservation was assessed through image analysis using HisTOOLogy and compared with conventional DNA and total protein content assays. HisTOOLogy's performance was also compared with ImageJ's colour deconvolution plug-in, demonstrating its advantages in terms of ease of use and speed of colour separation. PMID- 26258895 TI - Analytical Challenge in Postmortem Toxicology Applied to a Human Body Found into a Lake after Three Years Immersion. AB - The body of a 30-year-old woman was found in Como lake at a depth of about 120 meters in her own car after 3 years of immersion. The aim of this study was to evaluate psychoactive drugs as well as alcohol biomarkers in biological matrices. The following analyses were initially performed: GC-MS systematic toxicological analysis on biological fluids and tissues; GC-MS analysis of drugs of abuse on pubic hair; direct ethanol metabolite determination in pubic hair by LC-MS/MS. After 7 years, the samples, that had been stored at -20 degrees C, were re analyzed and submitted to an LC-MS/MS targeted screening method, using multiple reaction monitoring mode. These analyses detected citalopram (150-3000 ng/mL), desmethylcitalopram (50-2300 ng/mL), clotiapine (20-65 ng/mL), and ethyl glucuronide (97 pg/mg). The methods showed an acceptable reproducibility, and the concentrations of citalopram and desmethylcitalopram calculated through the two analytical techniques did not significantly differ in biological fluids. PMID- 26258894 TI - DNA/RNA heteroduplex oligonucleotide for highly efficient gene silencing. AB - Antisense oligonucleotides (ASOs) are recognized therapeutic agents for the modulation of specific genes at the post-transcriptional level. Similar to any medical drugs, there are opportunities to improve their efficacy and safety. Here we develop a short DNA/RNA heteroduplex oligonucleotide (HDO) with a structure different from double-stranded RNA used for short interfering RNA and single stranded DNA used for ASO. A DNA/locked nucleotide acid gapmer duplex with an alpha-tocopherol-conjugated complementary RNA (Toc-HDO) is significantly more potent at reducing the expression of the targeted mRNA in liver compared with the parent single-stranded gapmer ASO. Toc-HDO also improves the phenotype in disease models more effectively. In addition, the high potency of Toc-HDO results in a reduction of liver dysfunction observed in the parent ASO at a similar silencing effect. HDO technology offers a novel concept of therapeutic oligonucleotides, and the development of this molecular design opens a new therapeutic field. PMID- 26258896 TI - Effect of Aggregatibacter actinomycetemcomitans from Aggressive Periodontitis patients on Streptococcus mutans. AB - OBJECTIVES: To determine in vivo association between Aggregatibacter actinomycetemcomitans (Aa) and Streptococcus mutans (Sm) in aggressive periodontitis patients (AgP) and the in vitro influence on Sm of saliva and of Aa strains isolated from individual Aa-positive patients. MATERIALS AND METHODS: Clinical indices and saliva samples were taken from 30 AgP patients. Aa and mutans streptococci levels were determined. Antibacterial effect of saliva from 12 Aa-positive patients, and their individual Aa strain, was checked turbidimetrically in vitro on Sm. RESULTS: Aa salivary level was inversely correlated with levels of mutans streptococci and directly correlated with pockets of >=7 mm. During exponential growth phase: (i) All Aa-positive and Aa negative saliva samples showed no significant influence on Sm growth. (ii) Each individually isolated Aa strain presented significant inhibitory effect on Sm growth. During stationary growth phase, all the above demonstrated an inhibitory effect on Sm growth, with significantly greater influence of Aa individual strains. CONCLUSION: Saliva of each AgP Aa-positive subject had an inhibitory effect on Sm growth, which is most likely derived from Aa bacterial physiology. This research raises the possibility that suppression of Aa due to periodontal treatment may increase Sm levels and hence caries incidence. PMID- 26258897 TI - A new flash-free orthodontic adhesive system: A first clinical and stereomicroscopic study. AB - OBJECTIVE: To analyze the clinical and laboratory properties of the recently introduced APC flash-free orthodontic adhesive. MATERIAL AND METHODS: After bonding of 80 brackets on human teeth (group A: APC flash-free adhesive n = 40, group B: APC Plus adhesive n = 40), the following measurements were recorded: time for bonding, stereomicroscopic evaluation of excess adhesive, color penetration (methylene blue, 0.5%/24 h), and Adhesive Remnant Index (ARI) score after debonding. RESULTS: The time needed for bonding differed significantly between the two groups (A: 19.5 s/tooth vs B: 33.8 s/tooth). The adhesive excess, which was metrically measured from the bracket edge, ranged from 166.27 um to 81.66 um (group A) and 988.53 um to 690.81 um (group B). After methylene coloration in group A, 52 of 80 measurements showed discoloration on the bracket adhesive and/or adhesive-enamel interface, while for group B, 78 of 80 were coloration positive. The ARI scores did not differ, with an average ARI score of 2.0 for group A and 2.8 for group B. CONCLUSION: The flash-free adhesive significantly reduced the time needed for the bonding process. The excess resin expanded 0.16 to 0.08 mm over the bracket margin. The new technology seems to facilitate a smooth and sufficient marginal surface of the adhesive, which clinically might improve reduction of plaque accumulation. PMID- 26258898 TI - Anchorage condition during canine retraction using transpalatal arch with continuous and segmented arch mechanics. AB - OBJECTIVE: To compare anchorage condition in cases in which transpalatal arch was used to enhance anchorage in both continuous and segmented arch techniques. MATERIALS AND METHODS: Twenty cases that required first premolar extraction for orthodontic treatment and transpalatal arch to enhance anchorage were included in this study. Ten cases were treated using the continuous arch technique, while the other 10 cases were treated using 0.019 * 0.025-inch TMA T-loops with posterior anchorage bend according to the Burstone and Marcotte description. Lateral cephalometric analysis of before and after canine retraction was performed using Ricketts analysis to measure the anteroposterior position of the upper first molar to the vertical line from the Pt point. Data were analyzed using an independent sample t-test. RESULTS: There was a statistically significant forward movement of the upper first molar in cases treated by continuous arch mechanics (4.5 +/- 3.0 mm) compared with segmented arch mechanics (-0.7 +/- 1.4 mm; P = .01). CONCLUSIONS: The posterior anchorage bend to T-loop used to retract the maxillary canine can enhance anchorage during maxillary canine retraction. PMID- 26258899 TI - Treatment effects of skeletally anchored Forsus FRD EZ and Herbst appliances: A retrospective clinical study. AB - OBJECTIVE: To evaluate the skeletal, dentoalveolar, and soft tissue effects of the Forsus FRD appliance with miniplate anchorage inserted in the mandibular symphyses and to compare the findings with a well-matched control group treated with a Herbst appliance for the correction of a skeletal Class II malocclusion due to mandibular retrusion. MATERIALS AND METHODS: The sample consisted of 32 Class II subjects divided into two groups. Group I consisted of 16 patients (10 females and 6 males; mean age, 13.20 +/- 1.33 years) treated using the Forsus FRD EZ appliance with miniplate anchorage inserted in the mandibular symphyses. Group II consisted of 16 patients (9 females and 7 males; mean age, 13.56 +/- 1.27 years) treated using the Herbst appliance. Seventeen linear and 10 angular measurements were performed to evaluate and compare the skeletal, dentoalveolar, and soft tissue effects of the appliances using paired and Student's t-tests. RESULTS: Both appliances were effective in correcting skeletal class II malocclusion and showed similar skeletal and soft tissue changes. The maxillary incisor was statistically significantly more retruded in the skeletally anchored Forsus FRD group (P < .01). The mandibular incisor was retruded in the skeletally anchored Forsus FRD group (-4.09 degrees +/- 5.12 degrees ), while it was protruded in the Herbst group (7.50 degrees +/- 3.98 degrees ) (P < .001). CONCLUSION: Although both appliances were successful in correcting the skeletal Class II malocclusion, the skeletally anchored Forsus FRD EZ appliance did so without protruding the mandibular incisors. PMID- 26258900 TI - Durable Response of Leptomeningeal Metastasis of Breast Cancer to Salvage Intrathecal Etoposide After Methotrexate: A Case Report and Literature Review. AB - BACKGROUND: Leptomeningeal metastasis (LM) is recently on the rise as one of important clinical issues in the management of metastatic breast cancer (MBC). Clinical research on salvage intrathecal chemotherapy after failure of first-line treatment for MBC patients with LM has rarely been reported. CASE REPORT: We report the case of a breast cancer patient with LM who showed durable response to salvage intrathecal etoposide subsequent to failure of methotrexate. Etoposide 1 mg was injected through an Ommaya reservoir every week. Corticosteroid was used for a prophylaxis of chemical arachnoiditis. The treatment was successful palliation of LM for 33 weeks without significant adverse effects. Time to neurologic progression was estimated to be about 230 days for the treatment and overall survival was 301 days from the diagnosis of LM. CONCLUSIONS: Intrathecal etoposide can be considered as an additional treatment option for LM in breast cancer. Further large clinical studies are necessary to investigate the effectiveness and safety of the treatment. PMID- 26258901 TI - Globus Pallidus Necrosis Unrelated to Carbon Monoxide Poisoning: Retrospective Analysis of 27 Cases of Basal Ganglia Necrosis. AB - Bilateral globus pallidus necrosis is said to be characteristic of carbon monoxide (CO) poisoning. However, there has been no scientific test of this hypothesis. To examine the assertion that globus pallidus necrosis is typical of CO poisoning, this study examined autopsy cases from the King County Medical Examiner's Office (KCMEO) between 1994 and 2013. Twenty-seven cases with bilateral basal ganglia lesions were identified and examined for associated or causative disease or injury with the following results: 10 cases of drug overdose, seven heart disease, three asphyxia, two chronic ethanolism, two Huntington-like disorder, and one case each of remote trauma, rheumatic heart disease, and cerebral artery gas embolism. Additionally, review of all known cases at KCMEO of CO poisoning found no evidence of globus pallidus or basal ganglia necrosis. Thus, this study provides no support for the assertion that globus pallidus necrosis is characteristic of CO poisoning. PMID- 26258902 TI - Development of an LC-MS/MS method for studying migration characteristics of acetaldehyde in polyethylene terephthalate (PET)-packed mineral water. AB - During storage, acetaldehyde migration from polyethylene terephthalate (PET) bottles can affect the quality of mineral water even in the low ug l(-1) range negatively, as it features a fruity or plastic-like off-flavour. For a sensitive and fast analysis of acetaldehyde in mineral water, a new analysis method of 2,4 dinitrophenylhydrazine (DNPH) derivatisation followed by HPLC-electrospray tandem mass spectrometry (ESI-MS/MS) was developed. Acetaldehyde was directly derivatised in the mineral water sample avoiding extraction and/or pre concentration steps and then analysed by reversed-phase HPLC-ESI-MS/MS using multiple reaction monitoring mode (MRM). Along with method development, the optimum molar excess of DNPH in contrast to acetaldehyde was studied for the mineral water matrix, because no specific and robust data were yet available for this critical parameter. Best results were obtained by using a calibration via the derivatisation reaction. Without any analyte enrichment or extraction, an LOD of 0.5 ug l(-1) and an LOQ of 1.9 ug l(-1) were achieved. Using the developed method, mineral water samples packed in PET bottles from Germany were analysed and the correlation between the acetaldehyde concentration and other characteristics of the samples was evaluated illustrating the applicability of the method. Besides a relationship between bottle size and CO2 content of the mineral water and acetaldehyde migration, a correlation with acetaldehyde migration and the material composition of the bottle, e.g. recycled PET, was noted. Investigating the light influence on the acetaldehyde migration with a newly developed, reproducible light exposure setup, a significant increase of the acetaldehyde concentration in carbonated mineral water samples was observed. PMID- 26258904 TI - Artificial Loading of ASC Specks with Cytosolic Antigens. AB - Inflammasome complexes form upon interaction of Nod Like Receptor (NLR) proteins with pathogen associated molecular patterns (PAPMS) inside the cytosol. Stimulation of a subset of inflammasome receptors including NLRP3, NLRC4 and AIM2 triggers formation of the micrometer-sized spherical supramolecular complex called the ASC speck. The ASC speck is thought to be the platform of inflammasome activity, but the reason why a supramolecular complex is preferred against oligomeric platforms remains elusive. We observed that a set of cytosolic proteins, including the model antigen ovalbumin, tend to co-aggregate on the ASC speck. We suggest that co-aggregation of antigenic proteins on the ASC speck during intracellular infection might be instrumental in antigen presentation. PMID- 26258906 TI - Foldable Transparent Substrates with Embedded Electrodes for Flexible Electronics. AB - We present highly flexible transparent electrodes composed of silver nanowire (AgNW) networks and silica aerogels embedded into UV-curable adhesive photopolymers (APPs). Because the aerogels have an extremely high surface-to volume ratio, the enhanced van der Waals forces of the aerogel surfaces result in more AgNWs being uniformly coated onto a release substrate and embedded into the APP when mixed with an AgNW solution at a fixed concentration. The uniform distribution of the embedded composite electrodes of AgNWs and aerogels was verified by the Joule heating test. The APP with the composite electrodes has a lower sheet resistance (Rs) and a better mechanical stability compared with APP without aerogels. The APP with the embedded electrodes is a freestanding flexible substrate and can be used as an electrode coating on a polymer substrate, such as polydimethylsiloxane and polyethylene terephthalate. On the basis of the bending test results, the APPs with composite electrodes were sufficiently flexible to withstand a 1 mm bending radius (rb) and could be foldable with a slight change in Rs. Organic light emitting diodes were successfully fabricated on the APP with the composite electrodes, indicating the strong potential of the proposed flexible TEs for application as highly flexible transparent conductive substrates. PMID- 26258903 TI - Cleaning Hospital Room Surfaces to Prevent Health Care-Associated Infections: A Technical Brief. AB - The cleaning of hard surfaces in hospital rooms is critical for reducing health care-associated infections. This review describes the evidence examining current methods of cleaning, disinfecting, and monitoring cleanliness of patient rooms, as well as contextual factors that may affect implementation and effectiveness. Key informants were interviewed, and a systematic search for publications since 1990 was done with the use of several bibliographic and gray literature resources. Studies examining surface contamination, colonization, or infection with Clostridium difficile, methicillin-resistant Staphylococcus aureus, or vancomycin-resistant enterococci were included. Eighty studies were identified-76 primary studies and 4 systematic reviews. Forty-nine studies examined cleaning methods, 14 evaluated monitoring strategies, and 17 addressed challenges or facilitators to implementation. Only 5 studies were randomized, controlled trials, and surface contamination was the most commonly assessed outcome. Comparative effectiveness studies of disinfecting methods and monitoring strategies were uncommon. Future research should evaluate and compare newly emerging strategies, such as self-disinfecting coatings for disinfecting and adenosine triphosphate and ultraviolet/fluorescent surface markers for monitoring. Studies should also assess patient-centered outcomes, such as infection, when possible. Other challenges include identifying high-touch surfaces that confer the greatest risk for pathogen transmission; developing standard thresholds for defining cleanliness; and using methods to adjust for confounders, such as hand hygiene, when examining the effect of disinfecting methods. PMID- 26258905 TI - TE = 32 ms vs TE = 100 ms echo-time (1)H-magnetic resonance spectroscopy in prostate cancer: Tumor metabolite depiction and absolute concentrations in tumors and adjacent tissues. AB - PURPOSE: To compare the depiction of metabolite signals in short and long echo time (TE) prostate cancer spectra at 3T, and to quantify their concentrations in tumors of different stage and grade, and tissues adjacent to tumor. MATERIALS AND METHODS: First, single-voxel magnetic resonance imaging (MRI) spectra were acquired from voxels consisting entirely of tumor, as defined on T2-weighted and diffusion-weighted (DW)-MRI and from a biopsy-positive octant, at TEs of 32 msec and 100 msec in 26 prostate cancer patients. Then, in a separate cohort of 26 patients, single-voxel TE = 32 msec MR spectroscopy (MRS) was performed over a partial-tumor region and a matching, contralateral normal-appearing region, defined similarly. Metabolite depiction was compared between TEs using Cramer-Rao lower bounds (CRLB), and absolute metabolite concentrations were calculated from TE = 32 msec spectra referenced to unsuppressed water spectra. RESULTS: Citrate and spermine resonances in tumor were better depicted (had significantly lower CRLB) at TE = 32 msec, while the choline resonance was better depicted at TE = 100 msec. Citrate and spermine concentrations were significantly lower in patients of more advanced stage, significantly lower in Gleason grade 3+4 than 3+3 tumors, and significantly lower than expected from the tumor fraction in partial-tumor voxels (by 14 mM and 4 mM, respectively, P < 0.05). CONCLUSION: Citrate and spermine resonances are better depicted at short TE than long TE in tumors. Reduction in these concentrations is related to increasing tumor stage and grade in vivo, while reductions in the normal-appearing tissues immediately adjacent to tumor likely reflect tumor field effects. PMID- 26258907 TI - Protein Activity Regulation: Inhibition by Closed-Loop Aptamer-Based Structures and Restoration by Near-IR Stimulation. AB - Regulation of protein activity is vital for understanding the molecular mechanism of biological activities. In this work, protein activity is suppressed by proximity-dependent surface hybridization and subsequently restored by near infrared (NIR) light stimulation. Specifically, by constructing closed-loop structures with two aptamer-based affinity ligands, significantly enhanced inhibition of thrombin activity is achieved compared to traditional single affinity ligand based inhibitors. Furthermore, the activity of inhibited thrombin is efficiently recovered under NIR light stimulation by using gold nanorods (AuNRs) as photothermal agents to disrupt the closed-loop structures. Real-time and in situ monitoring of the conversion of fibrinogen into fibrin catalyzed by both inhibited and recovered thrombin was performed with light scattering spectroscopy and laser scanning confocal microscopy (LSCM). Thrombin trapped in the closed-loop structures shows slow reaction kinetics, while the photothermally liberated thrombin displays largely recovered catalytic activity. Human plasma was further employed to demonstrate that both the inhibited and restored thrombin can be applied to clotting reaction in reality. This strategy provides protein activity regulation for studying the molecular basis of biological activities and can be further applied to potential areas such as metabolic pathway regulation and the development of protein-inhibitor pharmaceuticals. PMID- 26258908 TI - Estimating the Size of Hidden Populations Using Respondent-driven Sampling Data: Case Examples from Morocco. AB - BACKGROUND: Respondent-driven sampling is used worldwide to estimate the population prevalence of characteristics, such as HIV/AIDS and associated risk factors in hard-to-reach populations. Estimating the total size of these populations is of great interest to national and international organizations; however, reliable measures of population size often do not exist. METHODS: Successive sampling-population size estimation (SS-PSE) along with network size imputation allows population size estimates to be made without relying on separate studies or additional data (as in network scale-up, multiplier, and capture-recapture methods), which may be biased. RESULTS: Ten population size estimates were calculated for people who inject drugs, female sex workers, men who have sex with other men, and migrants from sub-Saharan Africa in six different cities in Morocco. SS-PSE estimates fell within or very close to the likely values provided by experts and the estimates from previous studies using other methods. CONCLUSIONS: SS-PSE is an effective method for estimating the size of hard-to-reach populations that leverages important information within respondent-driven sampling studies. The addition of a network size imputation method helps to smooth network sizes allowing for more accurate results. However, caution should be used particularly when there is reason to believe that clustered subgroups may exist within the population of interest or when the sample size is small in relation to the population. PMID- 26258909 TI - In Situ Activation of Nitrogen-Doped Graphene Anchored on Graphite Foam for a High-Capacity Anode. AB - We report the fabrication of a three-dimensional free-standing nitrogen-doped porous graphene/graphite foam by in situ activation of nitrogen-doped graphene on highly conductive graphite foam (GF). After in situ activation, intimate "sheet contact" was observed between the graphene sheets and the GF. The sheet contact produced by in situ activation is found to be superior to the "point contact" obtained by the traditional drop-casting method and facilitates electron transfer. Due to the intimate contact as well as the use of an ultralight GF current collector, the composite electrode delivers a gravimetric capacity of 642 mAh g(-1) and a volumetric capacity of 602 mAh cm(-3) with respect to the whole electrode mass and volume (including the active materials and the GF current collector). When normalized based on the mass of the active material, the composite electrode delivers a high specific capacity of up to 1687 mAh g(-1), which is superior to that of most graphene-based electrodes. Also, after ~90 s charging, the anode delivers a capacity of about 100 mAh g(-1) (with respect to the total mass of the electrode), indicating its potential use in high-rate lithium-ion batteries. PMID- 26258911 TI - The length and content of general practice consultation in two urban districts of Beijing: a preliminary observation study. AB - BACKGROUND: Community health service center (CHSC) and community health service station (CHSS) are the main institutions where general practitioners (GPs) deliver primary care in the urban area of China. Motivated by incentive policies, visits to community health service institutions (CHSIs) increased gradually in recent years, but concerns had been raised on the quality of general practice consultation. This is a preliminary study aimed to investigate the existing problems of general practice consultation in Beijing and provide practical evidence for developing relevant policies. METHODS: Six GPs from 2 CHSCs and 3 CHSSs were selected by purposive sampling. The GPs were observed for 4 or 5 consecutive days during January 2013 to March 2013. The length and content of consultations were recorded in structured observation forms. Quantitative description was applied to describe the median, percentage and frequency of variables. RESULTS: A total of 1135 consultations were observed. The most frequent reason for consultations was specific prescription (61.6%), followed by presenting symptoms (20.7%), check-up (9.1%), counseling (5.4%), transfusion & injection (3.0%) and sickness certificate (0.2%). The median consultation length of all consultations was 2.0 minutes. The GPs prescribed in 81.0% of the consultations, on the other hand, history taking, physical examination, explanation of illness and health education only took place in 27.0%, 28.0%, 21.9% and 17.7% of the consultations respectively. CONCLUSIONS: The adequacy of consultation length in CHSIs is in doubt. Most patients visited the CHSIs for prescription renewal. Health promotion e.g. health education are not adequately provided in consultations. The quality of general practice consultations was jeopardized by the large amount of patient flow for medicine renewal. Policies should be adjusted to reduce unnecessary consultations. Further studies are in need to evaluate the outcome and influencing factors of general practice consultation in China. PMID- 26258910 TI - An evolution in switching therapy for psoriasis patients who fail to meet treatment goals. AB - Switching psoriasis treatment is a common, accepted practice that is used to improve disease management and improve patient outcomes (e.g., when patients are experiencing suboptimal efficacy and/or tolerability with a given therapy). Historically, switching treatment was often performed to limit patients' cumulative exposure to conventional systemic agents (e.g., methotrexate, cyclosporine) with the goal of reducing end-organ toxicity. However, the practice of switching treatments has evolved in recent years with the availability of highly effective and tolerable biologic agents. In current practice, near complete skin clearance with minimal side effects should be a realistic treatment goal for most patients with moderate-to-severe psoriasis, and consideration for switching therapies has shifted to become more focused on achieving maximum possible skin clearance, enhanced quality of life, and improved patient satisfaction. This review provides a discussion of recent guidance on switching psoriasis therapies, including initial considerations for when switching therapy may be advisable and challenges associated with switching therapy, along with an overview of published clinical studies evaluating outcomes associated with switching therapy. The goal of this review is to empower dermatologists to optimally manage their patients' psoriasis by providing the tools needed to develop rational strategies for switching treatments based on the pharmacologic characteristics of available treatments and each patient's clinical needs and treatment preferences. PMID- 26258912 TI - Weight gain after oophorectomy among women with a BRCA1 or BRCA2 mutation. AB - AIM: To measure weight gain among unaffected women with a BRCA1 or BRCA2 mutation after undergoing an oophorectomy. PATIENTS & METHODS: We compared the bodyweight of women with (n = 405) and without an oophorectomy (n = 741) at baseline as well as the rate of weight change prior to and following surgery among 1454 BRCA mutation carriers who had an oophorectomy. RESULTS: There was a small and non significant difference in bodyweight between BRCA mutation carriers who had an oophorectomy compared with those women who did not (151.5 vs 149.1 pounds; p = 0.26). There was an increase in bodyweight with increasing age, but this relationship did not differ prior to and following surgery (p comparing the slope parameters = 0.78). CONCLUSION: Oophorectomy is not associated with significant weight gain in high-risk women. PMID- 26258913 TI - A Longitudinal Study on Human Outdoor Decomposition in Central Texas. AB - The development of a methodology that estimates the postmortem interval (PMI) from stages of decomposition is a goal for which forensic practitioners strive. A proposed equation (Megyesi et al. 2005) that utilizes total body score (TBS) and accumulated degree days (ADD) was tested using longitudinal data collected from human remains donated to the Forensic Anthropology Research Facility (FARF) at Texas State University-San Marcos. Exact binomial tests examined the rate of the equation to successfully predict ADD. Statistically significant differences were found between ADD estimated by the equation and the observed value for decomposition stage. Differences remained significant after carnivore scavenged donations were removed from analysis. Low success rates for the equation to predict ADD from TBS and the wide standard errors demonstrate the need to re evaluate the use of this equation and methodology for PMI estimation in different environments; rather, multivariate methods and equations should be derived that are environmentally specific. PMID- 26258914 TI - Lymphadiposal Flaps and Lymphaticovenular Anastomoses for Severe Leg Edema: Functional Reconstruction for Lymph Drainage System. AB - BACKGROUND: Collecting lymphatics have lymph-drainage function with contraction of smooth muscle cells. Patients with edema have lost this drainage function due to degeneration of smooth muscle cells. Lymphaticovenular (LV) anastomosis salvages smooth muscle cells from reversible degeneration (mild edema), but muscle cells cannot be recovered from irreversible degeneration (severe edema). Therefore, in severe edema, LV anastomoses cannot reestablish the drainage function of the lymphatic system.To overcome this weakness of LV bypass methods for severe edema, new methods were instituted for repair of this missing drainage function using a lymphadiposal flap from the contralateral foot for hemilateral edema, or transfer of lateral thoracic lymph nodes for bilateral edema. METHODS: A total of 13 cases were repaired with lymphadiposal flaps and additional LV anastomoses. These cases have frequent phlegmon or cellulitis or resisted to previous LV anastomoses and/or compression therapy. The ages ranged from 15 to 75 years. There were four cases of primary edema and nine cases of secondary edema. RESULTS: Regarding the lymphadiposal flap (n = 8), three cases showed an excellent response (37.5%; no need for compression therapy), four cases had a good response (50%; improvement with compression), one case showed no change (12.5%; no improvement), and there were no cases of deterioration. Regarding the lateral thoracic lymph nodes transfer (n = 5), two cases had a good response (40%), three showed no improvement (60%), and there were no cases of deterioration. CONCLUSION: It is concluded that lymphadiposal flap or lymph nodes transfer is suitable for severe edema having frequent cellulitis in unilateral or bilateral lower extremities resisting previous LV anastomoses and/or compression therapy. PMID- 26258915 TI - Usefulness of a Reconstructive Method for Oropharyngeal Defect Including the Larger Soft Palate with the Bent Anterolateral Thigh Flap. PMID- 26258916 TI - Combined Anterolateral Thigh and Anteromedial Thigh Flap for Extensive Extremity Reconstruction: Vascular Anatomy and Clinical Application. AB - BACKGROUND: The combined anterolateral thigh (ALT) and anteromedial thigh (AMT) flap has been previously reported for use in complicated head and neck reconstruction. However, it has not gained popularity due to the vascular variation. Here, we explore the vascular basis of this combined flap, and report its application in extremity reconstruction. METHODS: This study was divided into two parts: vascular anatomy and clinical application. In the anatomical study, 52 sides of adult thighs were dissected to identity vascular perforators supplying the combined ALT and AMT flap, with focus on sizeable perforators (larger than 0.5 mm) arising from the descending branch of the lateral circumflex femoral artery.Clinically, five male patients were treated by combined ALT and AMT flaps for extensive extremity reconstruction from January 2006 to December 2010. The mean age was 32 years (range, 23-45 years). The combined flap was used for covering large soft-tissue defects in forearm (n = 3) and calf (n = 2). For each patient, esthetic and functional results were recorded. RESULTS: The anatomical study showed that sizeable perforators supplying the ALT flap were present in 50 thighs (96.2%), and the perforators supplying the AMT flap were present in 32 thighs (61.5%). The combined ALT and AMT flaps were available in 30 thighs (57.7%).All five combined flaps survived completely. Skin grafts covering the donor sites healed uneventful. The mean follow-up was 9.6 months (range, 6-12 months). No complications were recorded during the follow-up. CONCLUSION: The combined ALT and AMT flap may be used for extensive extremity reconstruction in selected patients for its great maneuverability and acceptable donor-site morbidity. PMID- 26258917 TI - Striving for Normalcy after Lower Extremity Reconstruction with Free Tissue: The Role of Secondary Esthetic Refinements. AB - BACKGROUND: Many patients with successful lower extremity salvage have postoperative functional and esthetic concerns. Such concerns range from contour irregularity preventing proper shoe-fitting to esthetic concerns involving color, contour, and texture match. The purpose of this study is to determine the overall incidence as well as factors associated with an increased likelihood of undergoing secondary, esthetic refinements of lower extremity free flaps and to review current revision techniques. METHODS: All patients undergoing lower extremity soft tissue coverage for limb salvage procedures between January 2007 and June 2013 at a single institution were included in the analysis. Patients who underwent secondary refinements for lower extremity free flaps were compared with patients not undergoing secondary procedures. RESULTS: During the study period, 152 patients underwent reconstruction and were eligible for inclusion. Of these, 32 (21.1%) patients underwent secondary, esthetic revisions. Few differences in patient or case characteristics were noted, although revision patients trended toward being younger, having lower body mass index, with defects secondary to acute trauma located below the ankle. The most common revision was complex soft tissue rearrangement or surgical flap debulking/direct excision (87.5% of patients), followed by scar revision (12.5%), suction-assisted lipectomy (3.1%), laser scar revision (3.1%), and tissue expansion with local tissue rearrangement (3.1%). CONCLUSION: A significant portion of patients desire secondary revisions following the initial procedure. This is especially true of younger patients with below ankle reconstruction. In many patients, an esthetic consideration should not be of secondary concern, but should be part of the ultimate reconstructive algorithm for lower extremity limb salvage. PMID- 26258918 TI - To Resect or Not to Resect: The Effects of Rib-Sparing Harvest of the Internal Mammary Vessels in Microsurgical Breast Reconstruction. AB - BACKGROUND: The internal mammary vessels are the most commonly used recipients for microsurgical breast reconstructions. Often, the costal cartilage is sacrificed to obtain improved vessel exposure. In an effort to reduce adverse effects associated with traditional rib sacrifice, recent studies have described less-invasive, rib-sparing strategies. METHODS: After obtaining institutional review board's approval, a retrospective review of all patients undergoing microsurgical breast reconstruction at a single institution between November 2007 and December 2013 was conducted. Patients were divided into two cohorts for comparison: rib-sacrificing and rib-sparing internal mammary vessel harvests. RESULTS: A total of 547 reconstructions (344 patients) met inclusion criteria for this study. A total of 64.9% (n = 355) underwent rib-sacrificing internal mammary vessel harvest. Cohorts were similar in baseline patient characteristics, indications for surgery, and cancer therapies. However, patients undergoing rib sparing reconstructions had significantly shorter operative times (440 vs. 476 minutes; p < 0.01), and significantly less postoperative pain on postoperative day (POD) 1 (2.8/10 vs. 3.4/10; p = 0.033) and POD2 (2.4/10 vs. 3.0/10; p = 0.037). Furthermore, patients undergoing rib-sparing techniques had greater incidence of fat necrosis requiring excision (12.5 vs. 2.8%; p < 0.01) and a trend toward higher incidence of hematoma, venous thrombosis, and arterial thrombosis when compared with rib-sacrificing patients. CONCLUSIONS: Rib-sparing harvest of internal mammary vessels is a feasible technique in microsurgical breast reconstruction. However, given the significant increase in fat necrosis requiring surgical excision, the trend toward increased postoperative complications, and no significant difference in postoperative revision rates, the purported benefits of this technique may fail to outweigh the possible risks. PMID- 26258920 TI - Epidemiology of allergic conjunctivitis: clinical appearance and treatment patterns in a population-based study. AB - PURPOSE OF REVIEW: To analyse the most recently published studies on the prevalence of allergic conjunctivitis alone or in association with allergic rhinitis, and the clinical and demographic aspects of the disease. RECENT FINDINGS: Allergic conjunctivitis or conjunctival symptoms are present in 30-71% of patients with allergic rhinitis. Allergic conjunctivitis alone has been estimated in 6-30% of the general population and in up to 30% in children alone or in association with allergic rhinitis. Seasonal allergic conjunctivitis is the most frequent form; however, studies from tertiary, ophthalmology referral centers report that the chronic forms, such as vernal and atopic keratoconjunctivitis, are the most frequently seen by ophthalmologists. A recent large survey performed at a national level involving 304 ophthalmologists showed that the majority of patients with allergic conjunctivitis suffer annually of few episodes of mild ,intermittent conjunctivitis. However, 30% of patients are affected by frequent episodes with intense and persistent symptoms. Treatment is frequently not appropriate. SUMMARY: Even though allergic conjunctivitis is often associated to allergic rhinitis, epidemiology studies frequently do not include specific ophthalmological evaluations. An understanding of allergic conjunctivitis disease, its prevalence, demographics and treatment paradigms will provide important information towards understanding its pharmacoeconomics and burden on the national health systems. PMID- 26258921 TI - Epidemiology of food allergy and food-induced anaphylaxis: is there really a Western world epidemic? AB - PURPOSE OF REVIEW: Food-induced anaphylaxis continues to be an important cause of hospital admissions, particularly in children. This review outlines recent advances in understanding the epidemiology of IgE-mediated food allergy and potential mechanisms for its rise in prevalence. RECENT FINDINGS: The rise in food allergy prevalence in Western countries has happened more quickly than changes to the genome can occur; thus, environmental changes are likely to be important. Recent studies, however, suggest that genetic risk determines responses to environmental risk factors. Environmental peanut exposure has been associated with increased peanut allergy risk in individuals with filaggrin null mutations, consistently with sensitization occurring through a damaged skin barrier. Reduced microbial and vitamin D exposure is also leading candidates for risk factors for food allergy in the context of genetic susceptibility. In addition, HLA-DR and HLA-DQ gene region variants appear to play a role in peanut allergy, although no studies have yet assessed their susceptibility to environmental cues. Finally, findings from observational cohorts and the first large-scale intervention trials for food allergy prevention support early oral allergen exposure to reduce the prevalence of specific food allergies, which is informing changes in public health guidelines at the population level. Further research will be required to assess the impact of these guideline changes on the population prevalence of food allergy. SUMMARY: New studies are providing important insights into the prevalence, causes, and mechanisms of food allergy. Recent findings are informing changes to population health guidelines in developed countries, which have the potential to halt or reverse the increase in food allergy prevalence. By contrast, food allergy in the developing world remains understudied. PMID- 26258919 TI - From genetics to treatment of eosinophilic esophagitis. AB - PURPOSE OF REVIEW: Eosinophilic Esophagitis (EoE) is an emerging chronic atopic disease. Recent advances in understanding its genetic and molecular biology pathogenesis may lead to a better management of the disease RECENT FINDINGS: EoE is an atopic disease. Most of the patients affected by EoE have other atopic diseases such as allergic rhinitis, asthma, IgE-mediated food allergies and/or atopic dermatitis. The local inflammation is a T helper type 2 (Th2) flogosis, which most likely is driven by a mixed IgE and n-IgE-mediated reaction to food and/or environmental allergens. Epidemiological studies show that EoE is an atopic disease with a strong genetic component. Genetic studies have shown that EoE is associated with single nucleotide polymorphism on genes, which are released by the epithelium and important in atopic inflammation such as thymic stromal lymphopoietin located (TSLP) close to the Th2 cytokine cluster [interleukin (IL)-4, IL-5, IL-13] on chromosome 5q22, Calpain 14, EMSY, and Eotaxin3. When the EoE diagnosis is made, it is imperative to control the local eosinophilic inflammation not only to give symptomatic relief to the patient, but also to prevent complications such as esophageal stricture and food impaction. SUMMARY: EoE is treated like many other atopic diseases with a combination of topical steroids and/or food antigen avoidance. The new understanding of EoE may lead to more specific and definitive treatments of EoE. PMID- 26258923 TI - Early predictors of asthma and allergy in children: the role of epigenetics. AB - PURPOSE OF REVIEW: Asthma and allergic diseases are among the most prevalent chronic noncommunicable diseases of childhood. Although epidemiologic studies suggest that asthma begins in the preschool years, the lack of firm diagnostic criteria to distinguish children who will wheeze only transiently during early life lower respiratory illnesses from children who will wheeze persistently and develop asthma prevents pinpointing the time at which disease truly begins. Epigenetic mechanisms link gene regulation to environmental cues and developmental trajectories. This article reviews, the search for epigenetic predictors of asthma and/or allergy that can be identified already at birth and/or in early life. RECENT FINDINGS: DNA methylation signatures associated with asthma and/or allergy at birth, and time-dependent DNA methylation signatures associated with allergic disease phenotypes in early life have been identified. SUMMARY: The identification of early epigenetic predictors of allergic diseases points to a potential role of epigenetic mechanisms in regulating the inception of and the susceptibility to these diseases. Predictive signatures to more accurately estimate a child's risk for asthma and allergy may improve childhood asthma diagnosis. Moreover, understanding the biological implications of these signatures may help elucidate novel disease pathways and endotypes. PMID- 26258922 TI - Linking immune responses with fibrosis in allergic eye disease. AB - PURPOSE OF REVIEW: Here, we explore an emerging theme in the literature, which is the role of dendritic cells in the causation of fibrosis. To fully appreciate this pathway to disease, we also review the most recent literature regarding dendritic cell biology as it pertains to ocular surface tissues. On the basis of this information, we propose a unifying hypothesis for how dendritic cells may cause conjunctival fibrosis in the allergy setting. RECENT FINDINGS: Work in models of airway remodeling and liver fibrosis has pointed to a potentially central role for dendritic cells in the pathobiology of fibrosis. Indeed, these cells are recognized as the most potent antigen-presenting cells, and as such activate T lymphocytes that are profibrotic under certain conditions. However, recent findings suggest a more direct role for dendritic cells, which opens up the possibility that a similar pathway may be relevant in the causation of conjunctival fibrosis, particularly in allergic eye disease. SUMMARY: Conjunctival fibrosis is a serious clinical concern and is associated with chronic inflammation of the ocular surface tissue, such as in allergic eye disease. Dendritic cells are required in mediating allergic disease by activating pathologic T lymphocytes. Recent findings pointing to a central role for dendritic cell in fibrosis may, however, mean that these cells could also be contributing directly to conjunctival fibrosis. If so, furthering our understanding of dendritic cells could lead to the identification of novel and more effective therapeutic strategies to treat this disease. PMID- 26258924 TI - Understanding probiotics' role in allergic children: the clue of gut microbiota profiling. AB - PURPOSE OF REVIEW: To investigate the functional role of gut microbiota in diet modulated diseases, evaluating probiotic administration effects by systems biology-driven approaches. Understanding the role of host-gut microbial and gut microbe-microbe interactions in either allergic and healthy children may assist in selecting effective and targeted probiotics for personalized therapies. RECENT FINDINGS: Food allergy shows a significant increase, especially in Western countries where growing epidemiological data indicate prevalence of small family groups, limited rate of infections in childhood compared with low-income countries, high consumption of sterile foods, hence stimulating a poor trigger of the gut immune system. Therefore, new therapeutic strategies to treat food allergy consist of probiotic administration since early life, thus modulating gut microbiota through immune system stimulation at the mucosal level. SUMMARY: Currently, new insights for probiotic selection should take into consideration both phenotyping and genotyping bacterial features and host-microbial cross-talk at gut level, by employing multicomponent systems biology approaches to unveil gut ecosystem dynamics in terms of bacteria phylotypes and their metabolic activities. Moreover, new food processes need to be considered to assess the actual performance of probiotic strains administered to allergic patients. The advent of high-performance platforms employing genomic- and mass spectrometry based techniques has opened new perspectives on the gut microbiota field, and may now serve as advanced tool to dynamically investigate the interplay between probiotics and gut microbiota ecology under allergic conditions. PMID- 26258925 TI - Environmental aeroallergens and allergic rhino-conjunctivitis. AB - PURPOSE OF REVIEW: The rising prevalence of allergy and of allergic rhino conjunctivitis is associated with changes in modern lifestyle. The current period of rapid development and consequent urbanization and migration, coupled with changes in climate, is facilitating a growth in rates of allergy. RECENT FINDINGS: Alterations to indoor and outdoor environments resulting from urbanization, industrialization, and climate change have significant implications for the prevalence and management of allergic rhino-conjunctivitis. Rising temperatures, precipitation and more extreme weather enable longer pollen seasons and greater viability of indoor and outdoor moulds and result in increased exposure to (and allergenic potential of) these aeroallergens. Outdoor air pollution is a major risk factor for rhino-conjunctivitis; key contributors are fuel combustion and dust storms because of changes in land-use and development. Further studies are needed to recognize and understand sources of indoor pollution including phthalates. SUMMARY: A better understanding of the role of environmental aeroallergens in allergic rhino-conjunctivitis is important to aid future management of allergic conjunctivitis. Strategies such as region-specific modelling of aeroallergens (pollens, air pollution) are required to predict and thus prevent exposure and to better inform appropriate childhood exposure and minimize lifelong effects. PMID- 26258926 TI - Corneal complications of vernal keratoconjunctivitis. AB - PURPOSE OF REVIEW: Vernal keratoconjunctivitis (VKC) is a severe bilateral chronic allergic inflammatory disease of the ocular surface. In most of the cases, the disease is limited to the tarsal conjunctiva and to the limbus. However, in the more severe cases, the cornea may be involved, leading to potentially sight threatening complications. Prompt recognition of these complications is crucial in the management of VKC, which is one of the most severe ocular allergic diseases. RECENT FINDINGS: A vicious cycle of inflammation occurs as a result of a set of reciprocal interactions between the conjunctiva and the cornea, which results in damage to the corneal epithelium and corneal stoma, and to the formation of shield ulcers and plaques, infectious keratitis, keratoconus, scarring, and limbal stem cell deficiency. These corneal complications can cause permanent decrease or loss of vision in children suffering from VKC. SUMMARY: Corneal complications in VKC are the result of an on going process of uncontrolled inflammation. Proper recognition of the corneal complications in VKC is crucial, as most of these can be managed or prevented by a combination of medical and surgical measures. PMID- 26258928 TI - Comparative Analysis of Different Methods of Modeling the Thermal Effect of Circulating Blood Flow During RF Cardiac Ablation. AB - Our aim was to compare the different methods of modeling the effect of circulating blood flow on the thermal lesion dimensions created by radio frequency (RF) cardiac ablation and on the maximum blood temperature. Computational models were built to study the temperature distributions and lesion dimensions created by a nonirrigated electrode by two RF energy delivery protocols (constant voltage and constant temperature) under high and low blood flow conditions. Four methods of modeling the effect of circulating blood flow on lesion dimensions and temperature distribution were compared. Three of them considered convective coefficients at the electrode-blood and tissue-blood interfaces to model blood flow: 1) without including blood as a part of the domain; 2) constant electrical conductivity of blood; and 3) temperature dependent electrical conductivity of blood (+2%/ degrees C). Method 4) included blood motion and was considered to be a reference method for comparison purposes. Only Method 4 provided a realistic blood temperature distribution. The other three methods predicted lesion depth values similar to those of the reference method (differences smaller than 1 mm), regardless of ablation mode and blood flow conditions. Considering the aspects of lesion size and maximum temperature reached in blood and tissue, Method 2 seems to be the most suitable alternative to Method 4 in order to reduce the computational complexity. Our findings could have an important implication in future studies of RF cardiac ablation, in particular, in choosing the most suitable method to model the thermal effect of circulating blood. PMID- 26258927 TI - Telepsychiatrists' Medication Treatment Strategies in the Children's Attention Deficit/Hyperactivity Disorder Telemental Health Treatment Study. AB - OBJECTIVE: The purpose of this study was to examine the prescribing strategies that telepsychiatrists used to provide pharmacologic treatment in the Children's Attention-Deficit/Hyperactivity Disorder (ADHD) Telemental Health Treatment Study (CATTS). METHODS: CATTS was a randomized controlled trial that demonstrated the superiority of a telehealth service delivery model for the treatment of ADHD with combined pharmacotherapy and behavior training (n=111), compared with management in primary care augmented with a telepsychiatry consultation (n=112). A diagnosis of ADHD was established with the Computerized Diagnostic Interview Schedule for Children (CDISC), and comorbidity for oppositional defiant disorder (ODD) and anxiety disorders (AD) was established using the CDISC and the Child Behavior Checklist. Telepsychiatrists used the Texas Children's Medication Algorithm Project (TCMAP) for ADHD to guide pharmacotherapy and the treat-to-target model to encourage their assertive medication management to a predetermined goal of 50% reduction in ADHD-related symptoms. We assessed whether telepsychiatrists' decision making about making medication changes was associated with baseline ADHD symptom severity, comorbidity, and attainment of the treat-to-target goal. RESULTS: Telepsychiatrists showed high fidelity (91%) to their chosen algorithms in medication management. At the end of the trial, the CATTS intervention showed 46.0% attainment of the treat-to-target goal compared with 13.6% for the augmented primary care condition, and significantly greater attainment of the goal by comorbidity status for the ADHD with one and ADHD with two comorbidities groups. Telepsychiatrists' were more likely to decide to make medication adjustments for youth with higher baseline ADHD severity and the presence of disorders comorbid with ADHD. Multiple mixed methods regression analyses controlling for baseline ADHD severity and comorbidity status indicated that the telepsychiatrists also based their decision making session to session on attainment of the treat-to-target goal. CONCLUSIONS: Telepsychiatry is an effective service delivery model for providing pharmacotherapy for ADHD, and the CATTS telepsychiatrists showed high fidelity to evidence-based protocols. PMID- 26258929 TI - Dynamic 3-D MR Visualization and Detection of Upper Airway Obstruction During Sleep Using Region-Growing Segmentation. AB - GOAL: We demonstrate a novel and robust approach for visualization of upper airway dynamics and detection of obstructive events from dynamic 3-D magnetic resonance imaging (MRI) scans of the pharyngeal airway. METHODS: This approach uses 3-D region growing, where the operator selects a region of interest that includes the pharyngeal airway, places two seeds in the patent airway, and determines a threshold for the first frame. RESULTS: This approach required 5 s/frame of CPU time compared to 10 min/frame of operator time for manual segmentation. It compared well with manual segmentation, resulting in Dice Coefficients of 0.84 to 0.94, whereas the Dice Coefficients for two manual segmentations by the same observer were 0.89 to 0.97. It was also able to automatically detect 83% of collapse events. CONCLUSION: Use of this simple semiautomated segmentation approach improves the workflow of novel dynamic MRI studies of the pharyngeal airway and enables visualization and detection of obstructive events. SIGNIFICANCE: Obstructive sleep apnea (OSA) is a significant public health issue affecting 4-9% of adults and 2% of children. Recently, 3-D dynamic MRI of the upper airway has been demonstrated during natural sleep, with sufficient spatiotemporal resolution to noninvasively study patterns of airway obstruction in young adults with OSA. This study makes it practical to analyze these long scans and visualize important factors in an MRI sleep study, such as the time, site, and extent of airway collapse. PMID- 26258931 TI - Early Warning of Acute Decompensation in Heart Failure Patients Using a Noncontact Measure of Stability Index. AB - OBJECTIVE: Hospitalization due to heart failure (HF) continues to be a major clinical and economic challenge. To reduce hospitalization, this paper proposes a novel home telemonitoring system for an early warning of acute decompensation in patients with chronic stable New York Heart Association class II-IV HF. METHODS: It is based on deriving nocturnal respiratory related time series using a noncontact radio-wave bio-motion sensor. The system generates an alert when there is a change in the underlying probability distribution of the time series which can be regarded as a surrogate marker of patient stability. RESULTS: The system's performance is evaluated using dual-site longitudinal data collected from 104 HF patients over 12-24 months. The system reported an average sensitivity of 0.62 to detect a change during an episode of acute decompensation and an average specificity of 0.67 on the blind validation set, when the frequency of alert was four weeks. The system also performed well to predict acute decompensation with an average sensitivity of 0.55 and specificity of 0.73 on the validation set, where an event window was defined as three weeks preceding an event. CONCLUSION: These results demonstrate that the design and implementation of such a system is a positive step toward developing noncontact systems capable of preventing acute decompensation, reducing readmissions to hospital and ensuring better quality of life for HF patients. PMID- 26258930 TI - Simulation-Based Design for Wearable Robotic Systems: An Optimization Framework for Enhancing a Standing Long Jump. AB - GOAL: Technologies that augment human performance are the focus of intensive research and development, driven by advances in wearable robotic systems. Success has been limited by the challenge of understanding human-robot interaction. To address this challenge, we developed an optimization framework to synthesize a realistic human standing long jump and used the framework to explore how simulated wearable robotic devices might enhance jump performance. METHODS: A planar, five-segment, seven-degree-of-freedom model with physiological torque actuators, which have variable torque capacity depending on joint position and velocity, was used to represent human musculoskeletal dynamics. An active augmentation device was modeled as a torque actuator that could apply a single pulse of up to 100 Nm of extension torque. A passive design was modeled as rotational springs about each lower limb joint. Dynamic optimization searched for physiological and device actuation patterns to maximize jump distance. RESULTS: Optimization of the nominal case yielded a 2.27 m jump that captured salient kinematic and kinetic features of human jumps. When the active device was added to the ankle, knee, or hip, jump distance increased to between 2.49 and 2.52 m. Active augmentation of all three joints increased the jump distance to 3.10 m. The passive design increased jump distance to 3.32 m by adding torques of 135, 365, and 297 Nm to the ankle, knee, and hip, respectively. CONCLUSION: Dynamic optimization can be used to simulate a standing long jump and investigate human robot interaction. SIGNIFICANCE: Simulation can aid in the design of performance enhancing technologies. PMID- 26258932 TI - Toward Quantitative Assessment of Rheumatoid Arthritis Using Volumetric Ultrasound. AB - GOAL: Rheumatoid arthritis (RA) is characterized by inflammation within the joint space as well as erosion or destruction of the bone surface. We believe that volumetric (3-D) ultrasound imaging of the joints in conjunction with automated image-analysis tools for segmenting and quantifying the regions of interest can lead to improved RA assessment. METHODS: In this paper, we describe our proposed algorithms for segmenting 1) the 3 -D bone surface and 2) the 3-D joint capsule region. We improve and extend previous 2-D bone extraction methods to 3-D and make our algorithm more robust to the intensity loss due to surface normals facing away from incident acoustic beams. The extracted bone surfaces coupled with a joint-specific anatomical model are used to initialize a coarse localization of the joint capsule region. The joint capsule segmentation is refined iteratively utilizing a probabilistic speckle model. RESULTS: We apply our methods on 51 volumes from 8 subjects, and validate segmentation results with expert annotations. We also provide the quantitative comparison of our bone detection with magnetic resonance imaging. These automated methods have achieved average sensitivity/precision rates of 94%/93% for bone surface detection, and 87%/83% for joint capsule segmentation. Segmentations of normal and inflamed joints are compared to demonstrate the potential of using proposed tools to assess RA pathology at the joint level. CONCLUSION: The proposed image-analysis methods showed encouraging results as compared to expert annotations. SIGNIFICANCE: These computer-assisted tools can be used to help visualize 3-D anatomy in joints and help develop quantitative measurements toward RA assessment. PMID- 26258933 TI - Novel Optical Position Sensing for Miniaturized Applications and Validation in a Total Artificial Heart. AB - GOAL: This paper describes the development and testing of various position sensing systems (PSSs) for miniaturized long-term applications with a focus on their validation in a total artificial heart (TAH). After a short description of the TAH's functioning principle, the special requirements for the PSS resulting from the application in a TAH are investigated. METHODS: Three PSS's were designed according to these requirements. A specially designed test method was used to first validate each PSS for general use in a miniaturized application. This test method validated the speed, resolution, and accuracy requirements for the PSS. In a second step, the PSS's were integrated in a TAH to measure its stroke position for the drive control. In this application, further requirements apart from miniaturization were considered. Each PSS's functionality in the TAH was validated in a mock circulation loop, which simulates the human circulatory system. RESULTS: Two of the three designed PSS's showed satisfactory results for all tested requirements inside the pump, whereas the third PSS did not operate properly at full-pump capacity. The best performing PSS was chosen for further use in the TAH. It performed up to a beat rate of 220 b/m. CONCLUSION: The extensive validation resulted in an accurate, miniature PSS for a TAH. SIGNIFICANCE: Besides the use in a TAH, the presented PSS's can be employed in a wide use of miniaturized applications. The introduced testing method allows the validation for general miniaturized applications, e.g., linear motor drives. PMID- 26258934 TI - Real-Time Respiratory Motion Analysis Using 4-D Shape Priors. AB - Respiratory motion analysis based on range imaging (RI) has emerged as a popular means of generating respiration surrogates to guide motion management strategies in computer-assisted interventions. However, existing approaches employ heuristics, require substantial manual interaction, or yield highly redundant information. In this paper, we propose a framework that uses preprocedurally obtained 4-D shape priors from patient-specific breathing patterns to drive intraprocedural RI-based real-time respiratory motion analysis. As the first contribution, we present a shape motion model enabling an unsupervised decomposition of respiration induced high-dimensional body surface displacement fields into a low-dimensional representation encoding thoracic and abdominal breathing. Second, we propose a method designed for GPU architectures to quickly and robustly align our models to high-coverage multiview RI body surface data. With our fully automatic method, we obtain respiration surrogates yielding a Pearson correlation coefficient (PCC) of 0.98 with conventional surrogates based on manually selected regions on RI body surface data. Compared to impedance pneumography as a respiration signal that measures the change of lung volume, we obtain a PCC of 0.96. Using off-the-shelf hardware, our framework enables high temporal resolution respiration analysis at 50 Hz. PMID- 26258936 TI - New Methods to Monitor Stair Ascents Using a Wearable Pendant Device Reveal How Behavior, Fear, and Frailty Influence Falls in Octogenarians. AB - GOALS: To investigate if the stair negotiation by older people during activities of daily life (ADL) can be accurately identified using a freely worn pendant device. To investigate how usual stair-ascent performances during ADL relate to clinical assessments and prospective falls. METHODS: ADL were recorded for 30 min by 52 community-dwelling older people (83 +/- 4 years) using a small pendant device. Classification accuracy was assessed using annotated video and four-fold cross validation. Correlations between sensor-derived stair-ascent features (comprising intensity, variability, and stability) and a battery of clinical tests (comprising physiological, psychological, health, and follow-up falls) were investigated. RESULTS: Accurate identification of stair events (99.8%, Kappa 0.92) was possible in both "frail" and "athletic" participants by scaling the barometer threshold to stair cadences. Cautious double-stepping strategy could be identified remotely. Stair-ascent performance was correlated with ascent strategy ( r = -0.67), age ( r = -0.44), concern about falling ( r = -0.43 ), fall-risk scores ( r = -0.41), processing speed ( r = -0.38), and contrast sensitivity ( r = 0.32). Follow-up falls were correlated with ascent stability ( r = -0.35). CONCLUSION: Remote analysis of stair ascents is feasible. In our healthy older people, outcomes appeared more related to mental rather than physiological factors. The ascent strategies we observed in some older people may have reflected an appropriate behavioral response to increased concerns about falling. SIGNIFICANCE: Given acceptance of wearable devices is increasing; reduced functional performance and altered strategies for undertaking ADL could soon be routinely tracked to augment health care. PMID- 26258935 TI - A Sparse Model Based Detection of Copy Number Variations From Exome Sequencing Data. AB - GOAL: Whole-exome sequencing provides a more cost-effective way than whole-genome sequencing for detecting genetic variants, such as copy number variations (CNVs). Although a number of approaches have been proposed to detect CNVs from whole genome sequencing, a direct adoption of these approaches to whole-exome sequencing will often fail because exons are separately located along a genome. Therefore, an appropriate method is needed to target the specific features of exome sequencing data. METHODS: In this paper, a novel sparse model based method is proposed to discover CNVs from multiple exome sequencing data. First, exome sequencing data are represented with a penalized matrix approximation, and technical variability and random sequencing errors are assumed to follow a generalized Gaussian distribution. Second, an iteratively reweighted least squares algorithm is used to estimate the solution. RESULTS: The method is tested and validated on both synthetic and real data, and compared with other approaches including CoNIFER, XHMM, and cn.MOPS. The test demonstrates that the proposed method outperform other approaches. CONCLUSION: The proposed sparse model can detect CNVs from exome sequencing data with high power and precision. Significance: Sparse model can target the specific features of exome sequencing data. The software codes are freely available at http://www.tulane.edu/ wyp/software/Exon_CNV.m. PMID- 26258937 TI - A Feedback Control Approach to Organic Drug Infusions Using Electrochemical Measurement. AB - GOAL: Target-controlled infusion of anesthesia is a closed-loop automated drug delivery method with a computer-aided control. Our goal is to design and test an automated drug infusion platform for propofol delivery in total intravenous anesthesia (TIVA) administration. METHODS: In the proposed method, a dilution chamber with first-order exponential decay characteristics was used to model the pharmacodynamics decay of a drug. The dilution chamber was connected to a flow system through an electrochemical cell containing an organic film-coated glassy carbon electrode as working electrode. To set up the feedback-controlled delivery platform and optimize its parameters, ferrocene methanol was used as a proxy of the propofol. The output signal of the sensor was connected to a PI controller, which prompted a syringe pump for feedback-controlled drug infusion. RESULTS: The result is a bench-top drug infusion platform to automate the delivery of a propofol based on the measurement of concentration with an organic film-coated voltammetric sensor. CONCLUSION: To evaluate the performance characteristics of the infusion platform, the propofol concentration in the dilution chamber was monitored with the organic film-coated glassy carbon electrode and the difference between the set and measured concentrations was assessed. The feasibility of measurement-based feedback-controlled propofol delivery is demonstrated and confirmed. SIGNIFICANCE: This platform will contribute to high-performance TIVA application of intravenous propofol anesthesia. PMID- 26258938 TI - Ultrasound-Based Detection of Fasciculations in Healthy and Diseased Muscles. AB - Involuntary muscle activations are diagnostic indicators of neurodegenerative pathologies. Currently detected by invasive intramuscular electromyography, these muscle twitches are found to be visible in ultrasound images. We present an automated computational approach for the detection of muscle twitches, and apply this to two muscles in healthy and motor neuron disease-affected populations. The technique relies on motion tracking within ultrasound sequences, extracting local movement information from muscle. A statistical analysis is applied to classify the movement, either as noise or as more coherent movement indicative of a muscle twitch. The technique is compared to operator identified twitches, which are also assessed to ensure operator agreement. We find that, when two independent operators manually identified twitches, higher interoperator agreement (Cohen's kappa) occurs when more twitches are present (kappa = 0.94), compared to a lower number (kappa = 0.49). Finally, we demonstrate, via analysis of receiver operating characteristics, that our computational technique detects muscle twitches across the entire dataset with a high degree of accuracy (0.83 < accuracy < 0.96). PMID- 26258939 TI - Semi-parametric spatial joint modeling of HIV and HSV-2 among women in Kenya. AB - Several diseases have common risk factors. The joint modeling of disease outcomes within a spatial statistical context may provide more insight on the interaction of diseases both at individual and at regional level. Spatial joint modeling allows for studying of the relationship between diseases and also between regions under study. One major approach for joint spatial modeling is the multivariate conditional autoregressive approach. In this approach, it is assumed that all the covariates in the study have linear effects on the multiple response variables. In this study, we relax this linearity assumption and allow some covariates to have nonlinear effects using the penalized regression splines. This model was used to jointly model the spatial variation of human immunodeficiency virus (HIV) and herpes simplex virus-type 2 (HSV-2) among women in Kenya. The model was applied to HIV and HSV-2 prevalence data among women aged 15-49 years in Kenya, derived from the 2007 Kenya AIDS indicator survey. A full Bayesian approach was used and the models were implemented in WinBUGS software. Both diseases showed significant spatial variation with highest disease burdens occurring around the Lake Victoria region. There was a nonlinear association between age of an individual and HIV and HSV-2 infection. The peak age for HIV was around 30 years while that of HSV-2 was about 40 years. A positive significant spatial correlation between HIV and HSV-2 was observed with a correlation of 0.6831(95% CI: 0.3859, 0.871). PMID- 26258940 TI - DNA tetrominoes: the construction of DNA nanostructures using self-organised heterogeneous deoxyribonucleic acids shapes. AB - The unique programmability of nucleic acids offers alternative in constructing excitable and functional nanostructures. This work introduces an autonomous protocol to construct DNA Tetris shapes (L-Shape, B-Shape, T-Shape and I-Shape) using modular DNA blocks. The protocol exploits the rich number of sequence combinations available from the nucleic acid alphabets, thus allowing for diversity to be applied in designing various DNA nanostructures. Instead of a deterministic set of sequences corresponding to a particular design, the protocol promotes a large pool of DNA shapes that can assemble to conform to any desired structures. By utilising evolutionary programming in the design stage, DNA blocks are subjected to processes such as sequence insertion, deletion and base shifting in order to enrich the diversity of the resulting shapes based on a set of cascading filters. The optimisation algorithm allows mutation to be exerted indefinitely on the candidate sequences until these sequences complied with all the four fitness criteria. Generated candidates from the protocol are in agreement with the filter cascades and thermodynamic simulation. Further validation using gel electrophoresis indicated the formation of the designed shapes. Thus, supporting the plausibility of constructing DNA nanostructures in a more hierarchical, modular, and interchangeable manner. PMID- 26258941 TI - Pif97, a von Willebrand and Peritrophin Biomineralization Protein, Organizes Mineral Nanoparticles and Creates Intracrystalline Nanochambers. AB - The formation of the mollusk nacre layer involves the assembly and organization of mineral nanoparticles into fracture-toughened mesoscale-sized aragonite tablets that possess intracrystalline nanoporosities. At least one nacre protein family, known as the framework proteome, is strategically located as part of a macromolecular coating around each nacre tablet and is believed to participate in tablet formation. Here, we report new studies of a recombinant form (rPif97) of a unique Japanese pearl oyster (Pinctada fucata) nacre framework biomineralization protein, Pif97. This unique protein possesses both a von Willlebrand factor type A domain (vWA, F23-Y161) and a Peritrophin A chitin-binding domain (PAC, E234 D298). rPif97 self-associates or aggregates to form amorphous protein phases that organize both amorphous and single-crystal calcium carbonate nanoparticles in vitro. Further, in the presence of nucleating calcite crystals, rPif97 protein phases deposit onto these crystals and become occluded over time, forming nanochambers within the crystal interior. The formation of these mineral modifying amorphous protein phases is linked to the presence of intrinsic disorder and amyloid-like cross-beta-strand aggregation-prone regions, and three dimensional modeling indicates that both the vWA and PAC domains are accessible for intermolecular interactions. Thus, the vWA- and PAC-containing Pif97 protein exhibits key functionalities that would allow its participation in mollusk nacre layer tablet assembly and porosity formation. PMID- 26258942 TI - A discrete chromatin loop in the mouse Tcra-Tcrd locus shapes the TCRdelta and TCRalpha repertoires. AB - The locus encoding the T cell antigen receptor (TCR) alpha-chain and delta-chain (Tcra-Tcrd) undergoes recombination of its variable-diversity-joining (V(D)J) segments in CD4(-)CD8(-) double-negative thymocytes and CD4(+)CD8(+) double positive thymocytes to generate diverse TCRdelta repertoires and TCRalpha repertoires, respectively. Here we identified a chromatin-interaction network in the Tcra-Tcrd locus in double-negative thymocytes that was formed by interactions between binding elements for the transcription factor CTCF. Disruption of a discrete chromatin loop encompassing the D, J and constant (C) segments of Tcrd allowed a single V segment to frequently contact and rearrange to D and J segments and dominate the adult TCRdelta repertoire. Disruption of this loop also narrowed the TCRalpha repertoire, which, we believe, followed as a consequence of the restricted TCRdelta repertoire. Hence, a single CTCF-mediated chromatin loop directly regulated TCRdelta diversity and indirectly regulated TCRalpha diversity. PMID- 26258943 TI - Selective Recognition of Phosphatidylcholine Lipids by a Biomimetic Calix[6]tube Receptor. AB - Phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs) are usually the most abundant phospholipids in membranes. Only a few examples of artificial macrocyclic receptors capable of binding these zwitterionic lipids were reported, and in most cases, their mode of action differs from that of natural receptors. NMR studies show that calix[6]arenes 4-6 behave as heteroditopic receptors that can efficiently bind 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) in nonpolar solvents. Similarly to natural systems, the recognition proceeds through the establishment of specific interactions with the zwitterionic head of the lipid. In a protic environment, calix[6]tube 4 binds DOPC much more strongly than 5 and 6, thanks to the higher acidity of its H-bonding thiourea groups and the better preorganization of its binding site. Moreover, 4 is reluctant to the corresponding PE, highlighting a unique selectivity for PCs over PEs. A high selectivity for DOPC over dodecylphosphocholine (DPC) was also observed, and computer modeling studies showed that it may likely originate from the curved shape of the tubular recognition system of 4, which is well-adapted to the native conformation of DOPC. From a biomimetic point of view, the complex 4?DOPC shows remarkable similarities with a natural complex formed between a PC and the human phosphatidylcholine transfer protein. PMID- 26258944 TI - In Reply: Chiari Severity Index: A Novel Grading System Intended for Preoperative Counseling. PMID- 26258945 TI - Guiding the Guardians and Other Participants in Shared Decision Making. PMID- 26258946 TI - Influence of Temperature, Relative Humidity, and Soil Properties on the Soil-Air Partitioning of Semivolatile Pesticides: Laboratory Measurements and Predictive Models. AB - Soil-air partition coefficient (Ksoil-air) values are often employed to investigate the fate of organic contaminants in soils; however, these values have not been measured for many compounds of interest, including semivolatile current use pesticides. Moreover, predictive equations for estimating Ksoil-air values for pesticides (other than the organochlorine pesticides) have not been robustly developed, due to a lack of measured data. In this work, a solid-phase fugacity meter was used to measure the Ksoil-air values of 22 semivolatile current- and historic-use pesticides and their degradation products. Ksoil-air values were determined for two soils (semiarid and volcanic) under a range of environmentally relevant temperature (10-30 degrees C) and relative humidity (30-100%) conditions, such that 943 Ksoil-air measurements were made. Measured values were used to derive a predictive equation for pesticide Ksoil-air values based on temperature, relative humidity, soil organic carbon content, and pesticide specific octanol-air partition coefficients. Pesticide volatilization losses from soil, calculated with the newly derived Ksoil-air predictive equation and a previously described pesticide volatilization model, were compared to previous results and showed that the choice of Ksoil-air predictive equation mainly affected the more-volatile pesticides and that the way in which relative humidity was accounted for was the most critical difference. PMID- 26258947 TI - Fruit and vegetable consumption and cardiovascular risk factors in older Chinese: the Guangzhou biobank cohort study. AB - OBJECTIVE: To examine the adjusted associations of fruit consumption and vegetable consumption with the Framingham score and its components in the non Western setting of Southern China, considering health status. METHOD: Linear regression was used to assess the cross-sectional associations of fruit and vegetable consumption with the Framingham score and its components, among 19,518 older Chinese (>=50 years) from the Guangzhou Biobank Cohort Study in Southern China (2003-2006), and whether these differed by health status. RESULTS: The association of fruit consumption with the Framingham score varied by health status (P-value<0.001), but not vegetable consumption (P-value 0.51). Fruit consumption was associated with a lower Framingham score (-0.04 per portions/day, 95% confidence interval (CI) -0.08 to -0.004) among participants in poor health, adjusted for age, sex, recruitment phase, socio-economic position and lifestyle. However, similarly adjusted, fruit consumption was associated with a higher Framingham score (0.05, 95% CI 0.02 to 0.09) among participants in good health, perhaps due to a positive association of fruit consumption with fasting glucose. Similarly adjusted, vegetable consumption was associated with a higher Framingham score (0.03, 95% CI 0.01 to 0.05) among all participants, with no difference by health status. CONCLUSION: This large study from a non-western setting found that fruit and vegetable consumption was barely associated with the Framingham score, or major CVD risk factors. PMID- 26258948 TI - Correction: factors associated with the perception of speed among recreational skiers. PMID- 26258949 TI - Application of beta-lactamase reporter fusions as an indicator of effector protein secretion during infections with the obligate intracellular pathogen Chlamydia trachomatis. AB - Chlamydia spp. utilize multiple secretion systems, including the type III secretion system (T3SS), to deploy host-interactive effector proteins into infected host cells. Elucidation of secreted proteins has traditionally required ectopic expression in a surrogate T3SS followed by immunolocalization of endogenous candidate effectors to confirm secretion by chlamydiae. The ability to transform Chlamydia and achieve stable expression of recombinant gene products has enabled a more direct assessment of secretion. We adapted TEM-1 beta lactamase as a reporter system for assessment of chlamydial protein secretion. We provide evidence that this system facilitates visualization of secretion in the context of infection. Specifically, our findings provide definitive evidence that C. trachomatis CT695 is secreted during infection. Follow-up indirect immunofluorescence studies confirmed CT695 secretion and indicate that this effector can be secreted at multiple points during the chlamydial developmental cycle. Our results indicate that the BlaM-fusion reporter assay will allow efficacious identification of novel secreted proteins. Moreover, this approach can easily be adapted to enable more sophisticated studies of the secretion process in Chlamydia. PMID- 26258951 TI - Influence of Secondary Interactions on the Structure, Sublimation Thermodynamics, and Solubility of Salicylate:4-Hydroxybenzamide Cocrystals. Combined Experimental and Theoretical Study. AB - Cocrystal screening of 4-hydroxybenzamide with a number of salicylates (salicylic acid, SA; 4-aminosalicylic acid, PASA; acetylsalicylic acid, ASA; and salicylsalicylic acid, SSA) was conducted to confirm the formation of two cocrystals, [SA+4-OHBZA] (1:1) and [PASA+4-OHBZA] (1:1). Their structures were determined using single-crystal X-ray diffraction, and the hydrogen-bond network topology was studied. Thermodynamic characteristics of salicylic acid cocrystal sublimation were obtained experimentally. It was proved that PASA cocrystallization with 4-OHBZA makes the drug more stable and prevents the irreversible process of decarboxylation of PASA resulting in formation of toxic 3 aminophenol. The pattern of non-covalent interactions in the cocrystals is described quantitatively using solid-state density functional theory followed by Bader analysis of the periodic electron density. It has been found that the total energy of secondary interactions between synthon atoms and the side hydroxyl group of the acid molecule in [SA+4-OHBZA] (1:1) and [PASA+4-OHBZA] (1:1) cocrystals is comparable to the energy of the primary acid-amide heterosynthon. The theoretical value of the sublimation enthalpy of [SA+4-OHBZA], 231 kJ/mol, agrees fairly well with the experimental one, 272 kJ/mol. The dissolution experiments with [SA+4-OHBZA] have proved that the relatively large cocrystal stability in relation to the stability of its components has a negative effect on the dissolution rate and equilibrium solubility. The [PASA+4-OHBZA] (1:1) cocrystal showed an enhancement of apparent solubility compared to that of the corresponding pure active pharmaceutical ingredient, while their intrinsic dissolution rates are comparable. PMID- 26258950 TI - Increased extra-pair paternity in broods of aging males and enhanced recruitment of extra-pair young in a migratory bird. AB - Despite keen interest in extra-pair mating in birds, its adaptive significance remains unresolved. Here, we use a multi-year dataset to test whether traits of a female's social mate influence her propensity to produce extra-pair offspring in a population of house wrens, and whether producing extra-pair young has consequences for a female's fitness through effects on offspring survival. Females were most likely to produce extra-pair offspring when paired with old males and when paired with males on poor-quality territories, although this latter effect was marginally nonsignificant. Among offspring, the cutaneous immunity of within-pair young decreased as the age of their sires increased, but cutaneous immunity of extra-pair young was not affected by the age of their extra pair sires or by the age of the males rearing them. Extra-pair offspring were more likely than within-pair offspring to return as breeding adults to the local population, with extra-pair sons being more likely to return as a breeder for multiple years. Our findings support the hypothesis that females produce extra pair offspring to enhance their inclusive fitness beyond what they are capable of given the male with which they are socially paired. PMID- 26258954 TI - Utility of Preoperative Upper Gastrointestinal Series in Laparoscopic Gastrostomy Tube Placement. AB - INTRODUCTION: An upper gastrointestinal (UGI) series is a standard preoperative test for patients being evaluated for gastrostomy tube placement. We have recently begun to question the value of the radiation-exposing series in patients who tolerate gastric feeds. MATERIALS AND METHODS: A retrospective review was conducted in patients who underwent laparoscopic gastrostomy tube placement between 2000 and 2012. Demographics, indication for gastrostomy tube, comorbidities, preoperative imaging, and nutrition were analyzed. Patients with foregut pathology and those who underwent prior gastrointestinal surgery were excluded. RESULTS: Among 695 patients who underwent laparoscopic gastrostomy tube placement, the most common indications were failure to thrive (53%), neurologic disorder (25%), and dysphagia (12%). A UGI series was obtained for 420 patients (60%). Of these, 96 were found to have abnormalities (reflux, aspiration, anatomic). However, only 2 of these patients (0.3%) had a change in management, with 1 patient undergoing the Ladd procedure and 1 having negative diagnostic laparoscopy for suspected malrotation. In the subset analysis of 256 patients tolerating goal gastric feeds, 161 (63%) had a preoperative UGI series with only 2 patients (1.2%) having a resultant change in operative management: 1 undergoing the Ladd procedure and 1 having negative diagnostic laparoscopy. Of the 275 patients who did not have a preoperative UGI series, 1 patient (0.4%) was found to have malrotation postoperatively after two coins became lodged in the duodenum. This patient subsequently underwent an elective Ladd procedure. CONCLUSIONS: We found minimal impact of an UGI series during evaluation for gastrostomy alone. These studies may be able to be reserved for those with clear clinical indications. PMID- 26258955 TI - Are Common Skin Diseases among Norwegian Dermatological Outpatients Associated with Psychological Problems Compared with Controls? An Observational Study. AB - Dermatological disease has been shown to be associated with psychological comorbidity. The aim of this observational study is to describe the distribution of skin disease and the prevalence of depression, anxiety and stress among Norwegian dermatological outpatients. Thirteen percent of outpatients had clinical anxiety compared with 3.7% of healthy controls, and 5.8% had clinical depression compared with 0.9% of controls. Adjusted odds ratio for clinical anxiety was 4.53 in patients compared with controls, and for clinical depression 6.25, which is much higher than previously described in a larger European study. Patients with tumours had less depression. Chronic inflammatory skin conditions had an especially high impact on patient's psychological wellbeing and should not be undervalued relative to, for instance, skin cancer in health strategies. These results argue strongly for including skin disease prevention and treatment in future health strategies. PMID- 26258952 TI - Concentration ranges of antibacterial cations for showing the highest antibacterial efficacy but the least cytotoxicity against mammalian cells: implications for a new antibacterial mechanism. AB - Antibacterial metal ions, such as Ag(+), Zn(2+) and Cu(2+), have been extensively used in medical implants and devices due to their strong broad spectrum of antibacterial activity. However, it is still a controversial issue as to whether they can show the desired antibacterial activity while being toxic to mammalian cells. It is very important to balance their antibacterial effectiveness with minimal damage to mammalian cells. Toward this end, this study is to identify the suitable concentrations of these three ions at which they can effectively kill two types of clinically relevant bacteria (Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli)) but show no obvious cytotoxicity on fibroblasts. Such concentration ranges are found to be 2.5 * 10(-7) M-10(-6) M, 10(-5) M-10(-4) M, and 10(-5) M-10(-4) M for Ag(+), Zn(2+), and Cu(2+), respectively. Investigation of their antibacterial mechanism shows that these three metal ions all show antibacterial property through a mechanism of damaging bacterial cell membranes by the generation of reactive oxygen species but surprisingly preserving the integrity of bacterial genomic DNA. The encouraging results indicate that antibacterial metal ions with controlled concentrations can bring considerable benefits to biomedical applications. PMID- 26258953 TI - Heavy metal transport by the CusCFBA efflux system. AB - It is widely accepted that the increased use of antibiotics has resulted in bacteria with developed resistance to such treatments. These organisms are capable of forming multi-protein structures that bridge both the inner and outer membrane to expel diverse toxic compounds directly from the cell. Proteins of the resistance nodulation cell division (RND) superfamily typically assemble as tripartite efflux pumps, composed of an inner membrane transporter, a periplasmic membrane fusion protein, and an outer membrane factor channel protein. These machines are the most powerful antimicrobial efflux machinery available to bacteria. In Escherichia coli, the CusCFBA complex is the only known RND transporter with a specificity for heavy metals, detoxifying both Cu(+) and Ag(+) ions. In this review, we discuss the known structural information for the CusCFBA proteins, with an emphasis on their assembly, interaction, and the relationship between structure and function. PMID- 26258956 TI - Xylanase Immobilized on Novel Multifunctional Hyperbranched Polyglycerol-Grafted Magnetic Nanoparticles: An Efficient and Robust Biocatalyst. AB - Although several strategies are now available for immobilization of enzymes to magnetic nanoparticles for bioapplications, little progresses have been reported on the use of dendritic or hyperbranched polymers for the same purpose. Herein, we demonstrated synthesis of magnetic nanoparticles supported hyperbranched polyglycerol (MNP/HPG) and a derivative conjugated with citric acid (MNP/HPG-CA) as unique and convenient nanoplatforms for immobilization of enzymes. Then, an important industrial enzyme, xylanase, was immobilized on the nanocarriers to produce robust biocatalysts. A variety of analytical tools were used to study the morphological, structural, and chemical properties of the biocatalysts. Additionally, the results of biocatalyst systems exhibited the substantial improvement of reactivity, reusability, and stability of xylanase due to this strategy, which might confer them a wider range of applications. PMID- 26258957 TI - Passivation Dynamics in the Anisotropic Deposition and Stripping of Bulk Magnesium Electrodes During Electrochemical Cycling. AB - Although rechargeable magnesium (Mg) batteries show promise for use as a next generation technology for high-density energy storage, little is known about the Mg anode solid electrolyte interphase and its implications for the performance and durability of a Mg-based battery. We explore in this report passivation effects engendered during the electrochemical cycling of a bulk Mg anode, characterizing their influences during metal deposition and dissolution in a simple, nonaqueous, Grignard electrolyte solution (ethylmagnesium bromide, EtMgBr, in tetrahydrofuran). Scanning electron microscopy images of Mg foil working electrodes after electrochemical polarization to dissolution potentials show the formation of corrosion pits. The pit densities so evidenced are markedly potential-dependent. When the Mg working electrode is cycled both potentiostatically and galvanostatically in EtMgBr these pits, formed due to passive layer breakdown, act as the foci for subsequent electrochemical activity. Detailed microscopy, diffraction, and spectroscopic data show that further passivation and corrosion results in the anisotropic stripping of the Mg {0001} plane, leaving thin oxide-comprising passivated side wall structures that demark the {0001} fiber texture of the etched Mg grains. Upon long-term cycling, oxide side walls formed due to the pronounced crystallographic anisotropy of the anodic stripping processes, leading to complex overlay anisotropic, columnar structures, exceeding 50 MUm in height. The passive responses mediating the growth of these structures appear to be an intrinsic feature of the electrochemical growth and dissolution of Mg using this electrolyte. PMID- 26258958 TI - Progesterone Exacerbates Short-Term Effects of Traumatic Brain Injury on Supragranular Responses in Sensory Cortex and Over-Excites Infragranular Responses in the Long Term. AB - Progesterone (P4) has been suggested as a neuroprotective agent for traumatic brain injury (TBI) because it ameliorates many post-TBI sequelae. We examined the effects of P4 treatment on the short-term (4 days post-TBI) and long-term (8 weeks post-TBI) aftermath on neuronal processing in the rodent sensory cortex of impact acceleration-induced diffuse TBI. We have previously reported that in sensory cortex, diffuse TBI induces a short-term hypoexcitation that is greatest in the supragranular layers and decreases with depth, but a long-term hyperexcitation that is exclusive to the supragranular layers. Now, adult male TBI-treated rats administered P4 showed, in the short term, even greater suppression in neural responses in supragranular layers but a reversal of the TBI induced suppression in granular and infragranular layers. In long-term TBI there were only inconsistent effects of P4 on the TBI-induced hyperexcitation in supragranular responses but infragranular responses, which were not affected by TBI alone, were elevated by P4 treatment. Intriguingly, the effects in the injured brain were almost identical to P4 effects in the normal brain, as seen in sham control animals treated with P4: in the short term, P4 effects in the normal brain were identical to those exercised in the injured brain and in the long term, P4 effects in the normal brain were rather similar to what was seen in the TBI brain. Overall, these results provide no support for any protective effects of P4 treatment on neuronal encoding in diffuse TBI, and this was reflected in sensorimotor and other behavior tasks also tested here. Additionally, the effects suggest that mechanisms used for P4 effects in the normal brain are also intact in the injured brain. PMID- 26258959 TI - Early versus late removal of the laryngeal mask airway (LMA) for general anaesthesia. AB - BACKGROUND: The laryngeal mask airway (LMA) is a safe and effective modality to maintain the airway for general anaesthesia during surgical procedures. The LMA is removed at the end of surgery and anaesthesia, when the patient maintains an adequate respiratory rate and depth. This removal of the LMA can be done either when the patient is deep under anaesthesia (early removal) or only after the patient has regained consciousness (late removal). It is not clear which of these techniques is superior. OBJECTIVES: The objective of this review was to compare the safety of LMA removal in the deep plane of anaesthesia (early removal) versus removal in the awake state (late removal) for participants undergoing general anaesthesia. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 8); MEDLINE (1966 to August 2014); EMBASE (1980 to August 2014); LILACS (1982 to August 2014); CINAHL (WebSPIRS; 1984 to August 2014); and ISI Web of Science (1984 to August 2014). We searched for ongoing trials through various trial registration websites. In addition, we searched conference proceedings and reference lists of relevant articles. SELECTION CRITERIA: We included randomized controlled trials (RCTs) on adults and children undergoing elective general anaesthesia using the LMA, that compared early removal of the LMA (defined as removal of the LMA in the deep plane of anaesthesia) versus late removal of the LMA (defined as removal of the LMA after the patient is awake). DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We used a random-effects model to generate forest plots from the data. MAIN RESULTS: We identified a total of 9188 citations and included 15 RCTs conducted on 2242 participants in this review. All trials used the LMA Classic in American Society of Anesthesiologists (ASA) physical status I or II for patients undergoing elective general anaesthesia. Children were enrolled in 11 trials and adults in five trials. None of the trials were of high methodological quality. Eight of the 15 studies had adequate generation of random sequence, whereas only one trial had adequate concealment of random sequence. Three trials had blinded the outcome assessor. Thus, the majority of the studies appeared to have a high risk of bias in the study design.Using the GRADE approach, we found low quality evidence that the risk of laryngospasm was similar with early removal of the LMA (3.3%) versus late removal (2.7%): risk ratio (RR) 1.23, 95% confidence interval (CI) 0.74 to 2.03; 11 trials, 1615 participants. The quality of evidence was very low that the risk of coughing was less after early removal (13.9%) than late removal (19.4%): RR 0.52, 95% CI 0.29 to 0.94; 11 trials, 1430 participants. The quality of evidence for the risk of desaturation was also very low; there was no difference between early removal (7.9%) and late removal (10.1%): RR 0.68, 95% CI 0.4 to 1.16; 13 trials, 2037 participants. We found low quality evidence that the risk of airway obstruction was higher with early removal (15.6%) compared to late removal of the LMA (4.6%): RR 2.69, 95% CI 1.32 to 5.5; eight trials, 1313 participants. AUTHORS' CONCLUSIONS: This systematic review suggests that current best evidence comparing early versus late removal of the LMA in participants undergoing general anaesthesia does not demonstrate superiority of either intervention. However, the quality of evidence available is either low or very low. There is a paucity of well designed RCTs and a need for large scale RCTs to demonstrate whether early removal or late removal of the LMA is better after general anaesthesia. PMID- 26258960 TI - 3D profilometric characterization of the aged skin surface using a skin replica and alicona Mex software. AB - The skin's surface is characterized by a network of furrows and wrinkles showing different height and depth. Different studies showed that processes such as aging, photo aging and cancer may alter dermal ultrastructure surface. The quantitative analysis of skin topography is a key point for understanding health condition of the skin. Here, for the first time, the skin fine structure was studied via a new approach where replica method was combined with Mex Alicona software and scanning electron microscopy (SEM). The skin texture of cheek and forearm were studied in 120 healthy sardinian volunteers. Patients were divided into three different aged groups. The skin areas of interest were reproduced by the silicone replica method, each replica was explored by SEM and digital images were taken. By using Mex Alicona software were created 3D imagine and a list of 24 surface texture parameters were obtained, of these the most representative were chosen in order to assess eventual changes between groups. The skin's texture of forearm and cheek showed a gradually loss of its typical polyhedric mesh with increasing age group. In particular, the photoexposition increased loss of dermal texture. At today, Alicona mex technology was exclusively used on palaeontology studies, our results showed that a deep analyze of skin texture was performed and support Mex alicona software as a new promising tool on dermatological research. This new analytical approach provided an easy and fast process to appreciate skin texture and its changes, by using high quality 3D dimension images. SCANNING 38:213-220, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26258963 TI - [Diagnostics and therapy of gout - editorial]. PMID- 26258964 TI - [Alveolar echinococcosis - rare cystic disease of the liver - editorial]. PMID- 26258962 TI - Transcription dynamically patterns the meiotic chromosome-axis interface. AB - Meiotic chromosomes are highly compacted yet remain transcriptionally active. To understand how chromosome folding accommodates transcription, we investigated the assembly of the axial element, the proteinaceous structure that compacts meiotic chromosomes and promotes recombination and fertility. We found that the axial element proteins of budding yeast are flexibly anchored to chromatin by the ring like cohesin complex. The ubiquitous presence of cohesin at sites of convergent transcription provides well-dispersed points for axis attachment and thus chromosome compaction. Axis protein enrichment at these sites directly correlates with the propensity for recombination initiation nearby. A separate modulating mechanism that requires the conserved axial-element component Hop1 biases axis protein binding towards small chromosomes. Importantly, axis anchoring by cohesin is adjustable and readily displaced in the direction of transcription by the transcriptional machinery. We propose that such robust but flexible tethering allows the axial element to promote recombination while easily adapting to changes in chromosome activity. PMID- 26258965 TI - [PEGASUS - Ticagrelor in secondary prevention on patients after a myocardial infarction]. AB - BACKGROUND: Ticagrelor is a P2Y12 receptor antagonist that has been shown to reduce ischemic events for up to a year after an acute coronary syndrome. The efficacy and safety of long-term ticagrelor therapy beyond 1 year after a myocardial infarction is unknown. METHODS: We randomized 21,162 patients with a history of myocardial infarction within the prior 1-3 years in a double-blind 1 : 1 : 1 fashion to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or placebo, all with low-dose aspirin, and followed them for a median of 33 months. The primary efficacy endpoint was the composite of cardiovascular death, myocardial infarction, or stroke. The primary safety endpoint was TIMI major bleeding. RESULTS: Both doses of ticagrelor significantly reduced the primary combined efficacy endpoint compared to placebo with Kaplan-Meier rates at 3 years of 7.85 % with ticagrelor 90 mg, 7.77 % with ticagrelor 60 mg, and 9.04 % with placebo (HR for ticagrelor 90 mg vs placebo 0.85, 95% CI 0.75-0.96, p = 0.0080; HR for ticagrelor 60 mg vs placebo 0.84, 95% CI 0.74-0.95, p = 0.0043). Rates of TIMI major bleeding were higher with ticagrelor (2.60 % for 90 mg, 2.30 % for 60 mg and 1.06 % for placebo, p < 0.001 for each dose against placebo); the rates of intracranial hemorrhage or fatal bleeding were 0.63 %, 0.71 % and 0.60 % in the 3 arms, respectively. CONCLUSIONS: Treatment of patients more than 1 year after a myocardial infarction with ticagrelor reduces the risk of cardi-ovascular death, myocardial infarction, or stroke, and increases the risk of major bleeding.Key words: myocardial infarction - secondary prevention - ticagrelor. PMID- 26258966 TI - [Diagnosing and therapy of gout]. AB - Gout is an inflammatory, metabolically conditioned crystal-induced disease. Prevalence of gout is on the increase. In clinical practice it is frequently wrongly diagnosed and the therapy of acute attacks in particular is not adequate. The first part of the publication discusses diagnostic possibilities of gouty arthritis. First of all the advantage of the analysis of synovial exudate and of direct evidence of crystals in the polarization microscope is emphasized. If the material for crystallographic analysis is not available, it is necessary to use a combination of clinical criteria as specified e.g. in the recommendations of the European League Against Rheumatism (EULAR). The second part focuses on the therapy of gout which is divided into the periods of asymptomatic hyperuricemia, acute gouty attack, intercritical and chronic tophaceous gout. Asymptomatic hyperuricemia is only treated when uricemia greater than 540 umol/l occur repeatedly, or when other risk factors and comorbidities are present. In the treatment of acute gouty attack its early start is more important than the choice of a preparation. Alternatives are NSA, colchicine or glucocorticoids. A newly regist-ered medicine for the treatment of refractory acute inflammation is the IL 1 inhibitor canakinumab. The treatment of hyperuricemia involves regimen and diet measures, abstinence and hypouricemic therapy. Available are the xanthine oxidase inhibitors, allopurinol and febuxostat; the latter is better suited for patients with moderate renal insufficiency. A new medicine for the treatment of severe refractory tophaceous gout is pegloticase.Key words: gouty arthritis - colchicine - nonsteroidal antirheumatic drugs. PMID- 26258961 TI - Transglutaminase is a tumor cell and cancer stem cell survival factor. AB - Recent studies indicate that cancer cells express elevated levels of type II transglutaminase (TG2), and that expression is further highly enriched in cancer stem cells derived from these cancers. Moreover, elevated TG2 expression is associated with enhanced cancer stem cell marker expression, survival signaling, proliferation, migration, invasion, integrin-mediated adhesion, epithelial mesenchymal transition, and drug resistance. TG2 expression is also associated with formation of aggressive and metastatic tumors that are resistant to conventional therapeutic intervention. This review summarizes the role of TG2 as a cancer cell survival factor in a range of tumor types, and as a target for preventive and therapeutic intervention. The literature supports the idea that TG2, in the closed/GTP-binding/signaling conformation, drives cancer cell and cancer stem cell survival, and that TG2, in the open/crosslinking conformation, is associated with cell death. PMID- 26258967 TI - [Rare case of cystic disease of the liver - alveolar echinococcosis of the liver]. AB - Alveolar echinococcosis is a rare parasitic disease, especially of liver, caused by larval stage of tapeworm Echinococcus multilocularis. At the end of the last century France, Germany, Austria and Switzerland were the most often regions with this disease, these days is this infection diagnosed also in our territory. We describe the case of the disease of the twenty-five years old male with nonspecific signs and hepatomegaly, who was diagnosed on the basis of imaging and laboratory sampling. Due to inoperability the patient is now in infectologist follow-up on a long-term treatment with albendazole. He is clinically stable, included in waiting list for liver transplantation.Key words: alveolar echinococcosis - benzimidazols - Echinococcus multilocularis - parasitic disease of liver. PMID- 26258968 TI - ["Stressful holiday" - takotsubo cardiomyopathy]. AB - Takotsubo cardiomyopathy (TTC) is an acute syndrome characterized by rapid onset of transient systolic dysfunction of the left ventricle. Symptoms, ECG and laboratory findings resemble acute coronary syndrome, from which TTC differs by the absence of coronary artery disease. In typical cases, TTC is triggered by exposure to unexpected stress and the clinical course and prognosis are very good. We present a case of a 63-year-old woman, in whom the onset of the disease was complicated by ventricular fibrillation. The patient recovered without sequelae thanks to immediate cardiopulmonary resuscitation and following care in a specialized cardiocenter, which involved also implantation of implantable cardioverter defibrillator to prevent sudden cardiac death. Takotsubo cardiomyopathy is an important entity in the differential diagnosis of acute coronary syndrome. Despite very good prognosis in most cases it should not be underestimated and it deserves careful attention and treatment which can prevent harmful complications.Key words: myocardial infarction - sudden cardiac death - takotsubo cardiomyopathy - ventricular fibrillation. PMID- 26258969 TI - [Guidelines of Czech Association for Thrombosis and Haemostasis of the Czech Medical Association of J. E. Purkyne for safety treatment with new oral anticoagulants (NOAC) - dabigatran etexilate, apixaban and rivaroxaban]. AB - There are presently new oral anticoagulants (NOAC) for prevention and the treatment of thromboembolic diseases and they are registered in CZ. It concerns of orally direct inhibitors of thrombin (dabigatran etexilate), inhibitors of factor Xa (apixaban, rivaroxaban), respectively, with advantage of some properties not being seen in "classical" anticoagulants. In the use of new anticoagulants, however, are some problems - such as laboratory monitoring in urgent situations of effective treatment and the absence of specific antidote - resolved. The text below brings indications, dosage of the drugs, their elimination, follow-up of efficacy of the treatment or risk of the bleeding as well as the therapy of bleeding complications.Key words: apixaban - dabigatran etexilate - NOAC - rivaroxaban. PMID- 26258970 TI - [The imaging of musculoskeletal manifestations and complications in diabetes mellitus]. AB - The musculoskeletal system is one of the major regions, where changes caused by diabetes mellitus (DM) are often encountered causing severe impairment of the quality of patients' lives. These changes have therefore become an important focus of diagnostic and therapeutic procedures, with imaging methods - both plain radiography, computed tomography (CT), magnetic resonance imaging (MRI) and to a lesser extent ultrasound (US), being their cornerstones. In the article the images of musculoskeletal (MSK) manifestations of diabetes mellitus are presented, structured into changes directly caused by DM, metabolic consequences of DM, syndromes with increased coincidence with DM and septic complications. The CT, MRI and radiographic images of both initial and extensive changes are being displayed as well as evolution of the changes in a radiographic series. The concerning pathophysiologic remarks are only basic, as they are not the primary focus of radiodiagnostics. In conclusion it is stated, that imaging of the MSK system in diabetic patients is a large issue in radiologic units serving internal medicine departments, that the imaging methods should be applied specifically and that the radiologic findings influence further management of the patients in many respects, but also, that in some diagnostic questions, namely concerning septic complications of the diabetic foot, a fully reliable and unequivocal interpretation is not always possible.Key words: diabetes mellitus - imaging - musculoskeletal system. PMID- 26258971 TI - [Continuing peripheral nerve blocks - benefit for orthopedic patients with diabetes mellitus?]. AB - There is increasing incidence of diabetes mellitus in population of developed countries. And there is also, together with this fact, an increasing frequency of surgical not only orthopedic procedures for diabetic complications or for other reasons. However, thanks to modern sophisticated perioperative approaches, diabetes itself is no longer main risk factor for worsening of perioperative morbidity and mortality. The organ complications of diabetes still remain the crucial for patients outcome. The individual approach to each patient is important when we are plann-ing anesthesiological perioperative strategy. Assessment of long term diabetes compensation before elective surgical procedures, assessment and optimization of organ functions with searching for possible secondary complications of diabetes is also crucial. Generally, it is necessary to maintain compensation of diabetes through the whole perioperative period, avoid episodes of hypotension and tissue hypoperfusion and all anesthesiological interventions have to be targeted to rapid recovery (chronic medication, oral feeding and early rehabilitation). Technics of regional anesthesia and peripheral nerve blocks particularly, may be very useful for the objective especially for ortho-pedic patients.Key words: anesthesia - diabetes mellitus - perioperative period - peripheral nerve blocks. PMID- 26258972 TI - [Perioperative care and diabetes]. AB - The perioperative care of diabetic patients is specific due to the necessity of adequate glycaemic correction, as well as owing to the occurrence of complications not taking place in nondiabetic patients. The present antidiabetic treatment therefore mostly needs to be adjusted to the perioperative period, but this is largely not necessary in the case of small and short surgeries. The perioperative care of diabetic patients must be carefully organized and scheduled. The main rules include adequate monitoring of blood glucose and insulin therapy, provision of nutrition and surgery performance in the morning.Key words: antidiabetic treatment - perioperative care of the diabetic patient. PMID- 26258973 TI - [Complications associated with joint replacements in diabetic patients]. AB - While a joint implant is the method of choice for numerous locomotor disorders and it is indicated for diabetic patients based on the same rules as for patients without diabetes mellitus, a joint implant in diabetic patients is associated with a high risk of perioperative complications. Considering a very difficult and demanding treatment of a deep infection of a joint replacement, the prevention of complications plays the key role. A precondition for adequate perioperative preparation and correctly managed perioperative and postoperative care of patients with diabetes mellitus is the close cooperation of the orthopedist, diabetologist and anesthesiologist, who in their practice have to respect the specificities of their diabetic patients presented in submitted reports.Key words: arthroplasty - complication - diabetes mellitus. PMID- 26258974 TI - [Obesity and orthopedic surgery, or else do mechanical complications of obesity exist?]. AB - Arthroses of weight-bearing joints and vertebrogenic problems are characteristic diseases of the obese. However the extreme risk is associated in particular with the combination with metabolic syndrome. Arthroses of bearing joints thus do not only present a mechanical complication of obesity, but also a metabolic complication. Similarly, the risk of venous thromboembolism which involves all orthopedic surgeries, is associated with both a rising BMI and hormonal condition (use of hormones and the like.). A joint replacement surgery can be typically performed on patients with a weight of up to 90 kg or BMI below 30. A preparation aimed at decreasing BMI to reach these values significantly reduces the risk of postoperative complications. However it is also necessary for the patient to maintain the reduced weight.Key words: diabetes mellitus - knee joint replacement - hip joint replacement - mechanical complications of obesity - metabolic complications of obesity - metabolic syndrome - obesity - surgery related risk - venous tromboembolizmus. PMID- 26258976 TI - [Diabetic neuropathy]. AB - The paper deals with one of microvascular complications of diabetes - diabetic polyneuropathy. It is discussed comprehensively from its causes, incidence, its classification and diagnostic possibilities to the risks it entails for patients and therapeutic possibilities.Key words: autonomic neuropathy - diabetes mellitus - diabetic neuropathy - motor neuropathy - sensitive neuropathy - diabetic foot syndrome. PMID- 26258975 TI - [Acute and chronic anticoagulation therapy in relation to joint replacements]. AB - Thromboembolic disease (TED) is a considerable social and health problem. The solution evidently consists in the prevention of TED in clinical fields, not in the treatment itself. We can assume that effective prevention consequently reduces the cost of the following treatment. A lethal pulmonary embolism (PE) can be the first and the final clinical manifestation in patients with an asymptomatic deep venous thrombosis. This makes the systematic prevention of venous thromboembolism in higher risk patients necessary. Unfortunately, pharmacological prevention has been used less than would be needed. Inseparable from the TED prevention are physical methods. Pharmacological possibilities of the thromboembolic disease prevention were significantly extended within the past decade. To ensure the TED prevention after the total replacement (TEP) of hip and knee joints the following rules need to be observed: the TED prevention should be effected with LMWH, fondaparinux, dabigatran, rivaroxaban or apixaban for a period of 28-35 days after the hip joint replacement surgery and for 14 days after the knee joint replacement. The use of ASA, dextran and UFH as a thromboprophylaxis after the hip and knee joint TEP is not justified within the Czech Republic. Physical means (graduated compression stockings or IPC) can be used to support the recommended pharmacological treatment, they should not be used individually except in cases where pharmacological thromboprophylaxis is contraindicated.Key words: apixaban - dabigatran - LMWH - rivaroxaban - total hip and knee joint replacement - thromboembolic disease. PMID- 26258977 TI - [Diabetic foot infections]. AB - Diabetic foot infections (DFIs) are serious problems in persons with diabetes, about 10 to 25 % of patients with dia-betes develop a foot ulcer and 60 % of them are infected. DFIs cause morbidity, limit mobility, worsen patients quality of life. Infections are classified as mild, moderate, or severe. Most DFIs are polymicrobial, with Gram-positive cocci (especially staphylococci), Gram-negative bacilli and obligate anaerobes. Successful therapy of DFI requires proper topical care and often includes surgical interventions but appropriate antibiotic treatment plays a key role. Initial antimicrobial therapy of these infections is usually empirical, the antibiotic regimen should be based on the severity of the infection. Definitive therapy should then be tailored according to the results of culture and susceptibility tests from a reliably obtained specimen. PMID- 26258978 TI - [Selected skin involvement of necrobiosis lipoidica type and skin and mucous membrane fungal infections in diabetes mellitus]. AB - Article reviews some skin and mucosal lesions associated with diabetes mellitus with focus on skin fungal infections and necrobiosis lipoidica.Key words: diabetes mellitus - necrobiosis lipoidica - skin and mucous membrane fungal infections in diabetes mellitus - skin involvement. PMID- 26258979 TI - [Application of stem cells in orthopedics]. AB - Regeneration of articular cartilage remains a major challenge in orthopaedics. Cell-based therapies (with chondrocyte and MSCs - mesenchymal stem cells) to augment cartilage repair have received considerable interest during recent years. Adipose MSCs have been used in the Czech Republic for osteoarthritis therapy, despite not being re-commended by the Czech Orthopaedic Association. This lecture reviews the studies and their level of evidence for orthopaedic routine therapy of osteoarthritis.Key words: mesenchymal stem cells - osteoarthritis. PMID- 26258980 TI - [Orthopedic surgical management of the diabetic foot]. AB - The basic prerequisite for the successful treatment of the diabetic foot is a multidisciplinary approach. Ideally, the diagnosis and treatment is managed by a podiatrist, who is also responsible for a cost-effective and well-managed setting. General concern of diabetics is the fear of losing a limb. On the basis of multidisciplinary approach is pos-sible to prevent major amputations in many cases, or in case of them to ensure the prosthetic and rehabilitation care. New possibilities of revascularization and cooperation with antibiotic centers increase the success of surgical treatment of diabetic foot syndrome. Surgical procedures could be divided into four classes: elective, prophylactic, curative, emergent. The aim of elective operations is the correction of painful deformities that are at risk for the formation of ulcers. Surgical procedures are the same as in non-diabetics. Prophylactic procedures comprises reconstruction of Charcot foot. Special surgical procedures described the concept of "superconstruct". Curative procedures help to heal ulcers when conservative treatment fails. Type of procedure is planned with regard of the extent of osteomyelitis and of the intervention in architectonics of the foot to prevent a recurrence of the ulcer. Emergent procedures are performed in case of acute infection. Radical revision of all affected compartments with evacuation of the abscesses, adequate antibiotic therapy and revascularization are essential.Key words: amputation - diabetic foot - Charcot neuroarthropathy - osteomyelitis. PMID- 26258981 TI - [Basic principles and difficulties relating to rehabilitation in diabetic patients following amputation]. AB - Vascular diseases as a result of diabetes mellitus are the most frequent indication for amputation in the Czech republic. Diabetic patients following amputation, unlike the other amputees, very frequently suffer multiple complications. These are both of general and local nature and pose a limitation to rehabilitation care as well as a prosthesis use. The main goal of therapeutic rehabilitation is the practice of locomotion with a prosthesis (artificial limb) and the patients full return to normal life. A team of closely cooperating specialists is involved. The rehabilitation care of amputees is divided into acute and aftercare. Within preoperative care we try to improve the patients physical and psychological condition. Following surgery we verticalize the patient as soon as possible depending on his/her possibilities and condition, we carry out breathing and vascular gymnastics and prevention of thromboembolic disease and we start the care of the stump. When the stump has been healed and shaped, the patient is provided with an artificial limb. The patients equipped with an artificial limb take a walking course where they learn how to handle the limb as well as walk indoors and outdoors and cope with common terrain unevenness.Key words: amputation - diabetes mellitus - walking with an artificial limb - prosthesis - lower limb prosthetics. PMID- 26258984 TI - Precision Screening for Colorectal Cancer: Promise and Challenges. PMID- 26258983 TI - Piezotransistive transduction of femtoscale displacement for photoacoustic spectroscopy. AB - Measurement of femtoscale displacements in the ultrasonic frequency range is attractive for advanced material characterization and sensing, yet major challenges remain in their reliable transduction using non-optical modalities, which can dramatically reduce the size and complexity of the transducer assembly. Here we demonstrate femtoscale displacement transduction using an AlGaN/GaN heterojunction field effect transistor-integrated GaN microcantilever that utilizes piezoelectric polarization-induced changes in two-dimensional electron gas to transduce displacement with very high sensitivity. The piezotransistor demonstrated an ultra-high gauge factor of 8,700 while consuming an extremely low power of 1.36 nW, and transduced external excitation with a superior noise limited resolution of 12.43 fm Hz(-1/2) and an outstanding responsivity of 170 nV fm(-1), which is comparable to the optical transduction limits. These extraordinary characteristics, which enabled unique detection of nanogram quantity of analytes using photoacoustic spectroscopy, can be readily exploited in realizing a multitude of novel sensing paradigms. PMID- 26258982 TI - ATP Binding Cassette Transporter Mediates Both Heme and Pesticide Detoxification in Tick Midgut Cells. AB - In ticks, the digestion of blood occurs intracellularly and proteolytic digestion of hemoglobin takes place in a dedicated type of lysosome, the digest vesicle, followed by transfer of the heme moiety of hemoglobin to a specialized organelle that accumulates large heme aggregates, called hemosomes. In the present work, we studied the uptake of fluorescent metalloporphyrins, used as heme analogs, and amitraz, one of the most regularly used acaricides to control cattle tick infestations, by Rhipicephalus (Boophilus) microplus midgut cells. Both compounds were taken up by midgut cells in vitro and accumulated inside the hemosomes. Transport of both molecules was sensitive to cyclosporine A (CsA), a well-known inhibitor of ATP binding cassette (ABC) transporters. Rhodamine 123, a fluorescent probe that is also a recognized ABC substrate, was similarly directed to the hemosome in a CsA-sensitive manner. Using an antibody against conserved domain of PgP-1-type ABC transporter, we were able to immunolocalize PgP-1 in the digest vesicle membranes. Comparison between two R. microplus strains that were resistant and susceptible to amitraz revealed that the resistant strain detoxified both amitraz and Sn-Pp IX more efficiently than the susceptible strain, a process that was also sensitive to CsA. A transcript containing an ABC transporter signature exhibited 2.5-fold increased expression in the amitraz resistant strain when compared with the susceptible strain. RNAi-induced down regulation of this ABC transporter led to the accumulation of metalloporphyrin in the digestive vacuole, interrupting heme traffic to the hemosome. This evidence further confirms that this transcript codes for a heme transporter. This is the first report of heme transport in a blood-feeding organism. While the primary physiological function of the hemosome is to detoxify heme and attenuate its toxicity, we suggest that the use of this acaricide detoxification pathway by ticks may represent a new molecular mechanism of resistance to pesticides. PMID- 26258985 TI - Pulp tissue response to Portland cement associated with different radio pacifying agents on pulpotomy of human primary molars. AB - The objective of this research was to evaluate the response of Portland cement associated with different radio pacifying agents on pulp treatment of human primary teeth by clinical and radiographic exams and microscopic analysis. Thirty mandibular primary molars were randomly divided into the following groups: Group I - Portland cement; Group II - Portland cement with iodoform (Portland cement + CHI3 ); Group III - Portland cement with zirconium oxide (Portland cement + ZrO2 ); and treated by pulpotomy technique (removal of a portion of the pulp aiming to maintain the vitally of the remaining radicular pulp tissue using a therapeutic dressing). Clinical and radiographic evaluations were recorded at 6, 12 and 24 months follow-up. The teeth at the regular exfoliation period were extracted and processed for histological analysis. Data were tested using statistical analysis with a significance level of 5%. The microscopic findings were descriptively analysed. All treated teeth were clinically and radiographically successful at follow-up appointments. The microscopic analysis revealed positive response to pulp repair with hard tissue barrier formation and pulp calcification in the remaining roots of all available teeth. The findings of this study suggest that primary teeth pulp tissue exhibited satisfactory biological response to Portland cement associated with radio pacifying agents. However, further studies with long term follow-up are needed to determine the safe clinical indication of this alternative material for pulp therapy of primary teeth. PMID- 26258986 TI - Knockdown of EHF inhibited the proliferation, invasion and tumorigenesis of ovarian cancer cells. AB - Ovarian cancer is the most lethal gynecologic malignancy worldwide. ETS homologous factor (EHF), a member of E26 transformation specific (ETS) transcription factors, has been reported overexpressed in ovarian cancer. However, the molecular mechanism underlying the biological function of EHF in ovarian cancer is still unclear. Here, we found that EHF was elevated in ovarian cancer tissues compared with non-tumorous tissues. Moreover, high EHF expression level was correlated with short survival time of patients with ovarian cancer. Knockdown of EHF in ovarian cancer cells, SKOV3 and OVCAR3, significantly inhibited cell proliferation and increased cells population in G1 phase. The proteins promoting cell cycles (Cyclin B1, Cyclin D1, and PCNA) were down regulated and the protein negatively regulating cell cycle progression (P21) was up-regulated after EHF knockdown. Moreover, inhibition of EHF in ovarian cancer cells dramatically induced cell apoptosis, but impaired cell adhesion and cell invasion. Furthermore, phosphorylation levels of ERK and AKT were notably reduced in EHF knockdown cells. Finally, in vivo data showed that knockdown of EHF inhibited tumor growth in nude mice. Our data indicates that EHF could be a potential prognosis marker for ovarian cancer and work as an oncogene by targeting ERK and AKT signaling, which can serve as a new target for ovarian cancer treatment. (c) 2015 Wiley Periodicals, Inc. PMID- 26258988 TI - Performance of a Non-Local van der Waals Density Functional on the Dissociation of H2 on Metal Surfaces. AB - van der Waals functionals have recently been applied to obtain a potential energy surface to describe the dissociation of H2 on Ru(0001), where an improvement was found for computed reaction probabilities compared to experiment, which could not be achieved with the use of other exchange-correlation functionals. It is, however, not yet clear to what extent van der Waals functionals give a better description of other molecule-metal surface systems. In this study, the optPBE vdW-DF functional is compared to the SRP48 functional, which was originally fitted to describe the dissociation of H2 on Cu(111), in terms of the resulting potential energy surfaces and results of quasi-classical dynamics calculations and their agreement with experiment for different H2-metal surface systems. It is found that overall the optPBE-vdW-DF functional yields potential energy surfaces that are very similar to potential energy surfaces computed with the SRP48 functional. In dynamics calculations the optPBE-vdW-DF functional gives a slightly better description of molecular beam experiments. Also a different dependence of reaction on the rotational quantum number J is found, which is in better agreement with experimental data for H2 dissociation on Cu(111). The vibrational efficacy is found to be relatively insensitive to which of the two functionals is chosen. PMID- 26258987 TI - Decoding genome-wide GadEWX-transcriptional regulatory networks reveals multifaceted cellular responses to acid stress in Escherichia coli. AB - The regulators GadE, GadW and GadX (which we refer to as GadEWX) play a critical role in the transcriptional regulation of the glutamate-dependent acid resistance (GDAR) system in Escherichia coli K-12 MG1655. However, the genome-wide regulatory role of GadEWX is still unknown. Here we comprehensively reconstruct the genome-wide GadEWX transcriptional regulatory network and RpoS involvement in E. coli K-12 MG1655 under acidic stress. Integrative data analysis reveals that GadEWX regulons consist of 45 genes in 31 transcription units and 28 of these genes were associated with RpoS-binding sites. We demonstrate that GadEWX directly and coherently regulate several proton-generating/consuming enzymes with pairs of negative-feedback loops for pH homeostasis. In addition, GadEWX regulate genes with assorted functions, including molecular chaperones, acid resistance, stress response and other regulatory activities. These results show how GadEWX simultaneously coordinate many cellular processes to produce the overall response of E. coli to acid stress. PMID- 26258989 TI - Complement activation product C4d in oral and oropharyngeal squamous cell carcinoma. AB - OBJECTIVE: Complement C4d-containing fragments have been proposed as diagnostic markers for lung cancer. The purpose of this study was to evaluate the presence of C4d in oropharyngeal (OPSCC) and oral (OSCC) squamous cell carcinomas. SUBJECTS AND METHODS: C4d staining was analyzed by immunohistochemistry in 244 OPSCC surgical specimens. C4d levels were quantified by ELISA in resting saliva samples from 48 patients with oral leukoplakia and 62 with OSCC. Plasma samples from 21 patients with leukoplakia and 30 with oral carcinoma were also studied. RESULTS: C4d staining in OPSCC specimens was associated with nodal invasion (P = 0.001), histopathologic grade (P = 0.014), disease stage (P = 0.040), and focal adhesion kinase expression (P < 0.001). No association was found between C4d and prognosis. Saliva C4d levels were higher in patients with oral cancer than in subjects with leukoplakia (0.07 +/- 0.07 vs 0.04 +/- 0.03 MUg ml(-1) , P = 0.003). The area under the ROC curve was 0.63 (95%CI: 0.55-0.71). Salivary C4d levels in stage IV patients were higher than in patients with earlier stages (P = 0.028) and correlated with tumor size (P = 0.045). Plasma C4d levels also correlated with salivary C4d levels (P = 0.041), but differences between patients with oral cancer and subjects with leukoplakia were not significant (1.26 +/- 0.59 vs 1.09 +/- 0.39 MUg ml(-1) , P = 0.232). CONCLUSION: C4d-containing fragments are detected in oral primary tumors and are increased in saliva from patients with OSCC. PMID- 26258990 TI - A Test of the DSP Sexing Method on CT Images from a Modern French Sample. AB - The hip bone is considered to be one of the most reliable indicators in sex determination. The aim of this study was to test the reliability of the DSP method for the hip bone proposed by Murail et al. (Bull Mem Soc Anthropol Paris, 17, 2005, 167) on a sample from a present-day population in France (52 males and 54 females). Ten linear measurements were collected from three-dimensional models derived from computed tomography images (CTI). To quantify the proportions of correct sex determinations, a more rigorous posterior probability threshold of 0.95 was applied. Using all 10 measurements, 92.3% of males and 97.2% of females were sexed correctly. The percentage of undetermined specimens varied depending on the used combination of measurements; however, all sexes were assigned with a 100% accuracy. This study proves that DSP is an appropriate and reliable tool for sex determination, based on dimensions obtained from CTI. PMID- 26258992 TI - Neuroretinal Degeneration in HIV Patients Without Opportunistic Ocular Infections in the cART Era. AB - Subtle structural and functional retinal abnormalities, termed 'HIV-associated Neuroretinal Disorder (HIV-NRD)', have been reported in HIV patients receiving combination antiretroviral therapy (cART), without infectious retinitis or any apparent fundus abnormalities otherwise. In this review, we provide an overview of studies investigating HIV-NRD in HIV patients without opportunistic ocular infections in the cART era, and try to elucidate underlying mechanisms and associated risk factors. Most studies focused on patients with severe immune deficiency and demonstrated that patients with nadir CD4 counts<100 cells/MUL are most at risk for neuroretinal damage, with a thinner retinal nerve fiber layer, subtle loss of color vision and/or contrast sensitivity, visual field deficits, and subnormal electrophysiological responses. In contrast, alterations in retinal vascular calibers and retinal blood flow were not associated with nadir CD4 counts, but instead with detectable viremia, suggesting a role for (chronic) inflammation in microvascular damage. Although the alterations in visual function are subtle, they can lead to difficulties in activities, such as reading or driving, thereby affecting quality of life. Since HIV has become a chronic disease, its long-term effects with respect to visual function loss become more important, as is recently emphasized by a longitudinal study, reporting that AIDS patients with HIV-NRD have higher risks of developing bilateral visual impairment and even blindness than patients without HIV-NRD. The question remains whether patients with high (>350 cells/MUL) nadir CD4 counts and well-suppressed HIV infection on cART remain at risk for HIV-NRD, as this group constitutes a growing part of the aging HIV-infected population. PMID- 26258991 TI - Fenofibrate Attenuates Neutrophilic Inflammation in Airway Epithelia: Potential Drug Repurposing for Cystic Fibrosis. AB - A hallmark of cystic fibrosis (CF) lung disease is neutrophilic airway inflammation. Elevated neutrophil counts have been associated with decreased forced expiratory volume in 1 second and poor clinical measures in patients with CF. Interleukin 8 (IL-8), epithelial neutrophil activating protein 78 (ENA-78), tumor necrosis factor alpha (TNF-alpha), granulocyte macrophage colony stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF) contribute to neutrophil activation and disease pathogenesis in the airways of patients with CF. Drugs that modify the production of these chemokines in the airways could potentially benefit CF patients. Thus, we determined the effects of fenofibrate on their production in cell populations obtained from the airways. Human small airway epithelial cells and CF bronchial epithelial cells were treated with IL-1beta to induce inflammation. We cotreated the cells with fenofibrate at concentrations ranging from 10 to 50 MUM to determine if this drug could attenuate the inflammation. IL-8, ENA-78, TNF-alpha, GM-CSF, and G-CSF production were measured from the cell culture supernates by ELISA. ANOVA statistical testing was conducted using SPSS 17.0. IL-1beta increased the production of each of the chemokines by several fold. Fenofibrate reduced IL 1beta induced production of each of these neutrophilic chemokines at the concentrations used. IL-1beta increases the production of neutrophilic chemokines in airway epithelial cells. Cotreatment with fenofibrate blunts these processes. Fenofibrate should be explored as a therapeutic option to modulate the abundant neutrophilic inflammation observed in CF. PMID- 26258993 TI - Giant Diaphragmatic Lipoma: Two Autopsy Case Reports and Review of the Literature. AB - Lipomas are common benign tumors most frequently found within the subcutaneous areas of the body. Deep-seated lipomas are rare and tend to be larger than cutaneous ones. Lipomas are rarely seen in the thoracic cavity, and they are usually located in the mediastinum, bronchiole, and lungs. Diaphragmatic lipomas have been occasionally reported in the literature, the first being described by Clark et al. in 1886. The authors report two rare cases of giant diaphragmatic lipoma incidentally found during forensic autopsies. In the first case, a Caucasian 85-year-old woman burned to death with another passenger, after her methane-fueled car collided with another car on a highway near Terni, Umbria, Italy. In the second case, a Caucasian 45-year-old man collapsed while walking through the countryside of Perugia. In either case, a large mass in the thorax was observed. The definitive pathologic diagnosis was giant intrathoracic diaphragmatic lipoma without evidence of malignancy. The authors also review the relevant literature and discuss differential diagnoses. These case reports contribute to the establishment of the actual incidence of diaphragmatic lipomas. PMID- 26258994 TI - Engaging Teens with Asthma in Designing a Patient-Centered Mobile App to Aid Disease Self-Management. AB - BACKGROUND: Despite the growing market of e-health disease self-management tools, few studies have reported the presence of teen patients in all phases of product design. While rates of American teens using mobile Internet grow, an opportunity to deliver disease self-management targeted for teen patients exists. Building on findings from previous investigations with teens with asthma, we explored teens' insights on the development of a patient-centered asthma management application (app). MATERIALS AND METHODS: Two existing asthma apps were used by 16 teen asthmatics for 7-10 days. At the end of the trial period, in-depth interviews were conducted with each participant to gather insights about the user experience. RESULTS: Participants requested more asthma-related content that educates them about their condition. Suggested improvements to currently available apps included a longer list of selectable symptoms to track, medication tracking, and more compelling interface features. CONCLUSIONS: Participants showed interest in using apps for managing their asthma, yet recommended improvements on current design. Whereas national figures point to a more ubiquitous mobile device environment, implementation efforts must respond to participants' recommendations while minding lingering digital divides. Currently available apps lack appealing components that teens seek or desire. Subsequent development should include teens' participation in component design insights. PMID- 26258995 TI - Inhibitory Effects of PEI-RGD/125I-(alphav) ASODN on Growth and Invasion of HepG2 Cells. AB - BACKGROUND: To investigate the in vitro inhibitory effects of PEI-RGD/125I (alphav)ASODN (PEI, polyethylenimine; RGD, Arg-Gly-Asp; ASODN, antisense oligodeoxynucleotide) on the growth and invasion of HepG2 cells. MATERIAL AND METHODS: ASODN of the integrin alphav-subunit was marked with 125I and underwent complexation with PEI-RGD, a PEI derivative. Next, PEI-RGD/125I-(alphav) ASODN was introduced into HepG2 cells via receptor-mediated transfection, and its inhibition rate on HepG2 cell growth was tested using the methyl thiazolyl tetrazolium (MTT) method. The effects of PEI-RGD/125I-(alphav) ASODN on HepG2 cell invasion ability were evaluated using the Boyden chamber assay. RESULTS: 1) The 125I marking rate of (alphav) ASODN was 73.78+/-4.09%, and the radiochemical purity was 96.68+/-1.38% (greater than 90% even after a 48-h incubation period at 37 degrees C), indicating high stability. 2) The cytotoxicity assays showed that the cell inhibition rates did not differ significantly between the PEI-RGD/125I (alphav)ASODN group and the PEI-RGD/(alphav) ASODN group, but they were both significantly higher than in the other groups and were positively correlated (r=0.879) with the dosage within a certain range. 3) The invasion assays showed that the inhibition rate was significantly greater in the PEI-RGD/125I-(alphav) ASODN group compared to the other groups. CONCLUSIONS: PEI-RGD/125I-(alphav) ASODN can efficiently inhibit the growth and proliferation of HepG2 cells and can also weaken their invasive ability. PMID- 26258996 TI - Background for Real-Time Monitoring and Intervention Related to Alcohol Use. AB - Real-time assessment, known as ecological momentary assessment (EMA), and real time intervention (ecological momentary intervention [EMI]) can significantly extend the reach and impact of interventions to help individuals reduce their drinking behavior. For EMA, the user provides information on the variable of interest (e.g., drinking or craving) via a mobile device.This data reporting can occur either at pre-specified times or in certain high-risk situations.The primary benefits of EMA include external validity, minimized recall bias, and the ability to capture dynamic patterns in human behavior. EMI refers to interventions that are delivered via mobile devices at the time when the user needs it (i.e., in a high-risk situation). Key constructs of EMI are what interventions are delivered and when they are delivered.The timing of the EMI often is determined by the user's EMA reports. Both EMA and EMI have been studied in people with alcohol use disorders. EMA and EMI often are used in conjunction with each other because EMA can help inform the optimal timing of EMI and help tailor its content. Further development of high-impact, algorithm-driven, technology-mediated real-time intervention may help reduce drinking and promote positive health behavior change. PMID- 26258997 TI - Using Ecological Momentary Assessment (EMA) to Assess Situation-Level Predictors of Alcohol Use and Alcohol-Related Consequences. AB - Ecological momentary assessment (EMA) has afforded several important advances in the field of alcohol research, including testing prominent models of alcohol abuse etiology in "high resolution." Using high-tech methods for signaling and/or assessment, such as mobile electronic diaries, personal data assistants, and smartphones, EMA approaches potentially can improve understanding of precipitants of drinking, drinking patterns, and consequences. For example, EMA has been used to study complex drinking patterns and dynamic predictors of drinking in near real time. Compared with other methods, EMA can better sample and capture changes in these phenomena that occur in relatively short time frames. EMA also has several potential applications in studying the consequences of alcohol use, including physical, interpersonal, behavioral, and legal problems. However, even with all these potential capabilities, EMA research in the alcohol field still is associated with some limitations, including the potential for measurement reactivity and problems with acceptability and compliance. Despite these limitations, electronically based EMA methods are versatile and are capable of capturing data relevant to a variety of momentary influences on both alcohol use and consequences. Therefore, it will be exciting to fully realize the potential of future applications of EMA technologies, particularly if the associated costs can be reduced. PMID- 26258998 TI - Tracking the When, Where, and With Whom of Alcohol Use: Integrating Ecological Momentary Assessment and Geospatial Data to Examine Risk for Alcohol-Related Problems. AB - Prevention researchers have found that drinking in different contexts is related to different alcohol problems. Where and with whom people drink affects the types of alcohol-related problems they experience. Consequently, identifying those contexts that result in the greatest number of problems provides a novel opportunity to target new prevention efforts aimed at those contexts. However, identifying these contexts poses methodological challenges to prevention research. To overcome these challenges, researchers need tools that allow them to gather detailed information about when and where people choose to drink and how contextual factors influence drinking risks. New data collection and analysis techniques, such as activity-space analysis, which examines movement through different contexts, and ecological momentary assessment, which captures microlevel contextual changes as individuals move through their days, can advance the field of alcohol studies by providing detailed information on the use of drinking contexts, particularly when combined. Data acquired through these methods allow researchers to better identify those con-texts where and conditions under which drinking and problems related to drinking occur. Use of these methods will allow prevention practitioners to target prevention efforts to those contexts that place most drinkers at risk and tailor prevention efforts to each context for specific outcomes. PMID- 26258999 TI - Biomonitoring for Improving Alcohol Consumption Surveys: The New Gold Standard? AB - To assess alcohol consumption levels in large populations, researchers often rely on self-report measures. However, these approaches are associated with several limitations, particularly underreporting. Use of noninvasive biomonitoring approaches may help validate self-report alcohol consumption measurements and thus improve their accuracy. Two such devices currently are available, the WrisTASTM and SCRAMTM devices, both of which measure alcohol vapors emitted through the skin after alcohol consumption. Several studies assessing the utility of the WrisTASTM bracelet in determining alcohol consumption levels noted that it was associated with relatively high failure rates. The SCRAMTM is an ankle bracelet intended for court-ordered alcohol monitoring. In studies, its sensitivity exceeded that of the WrisTASTM and increased with increasing blood alcohol concentrations. Although early studies also identified some equipment concerns with the SCRAMTM, studies of its ability to detect moderate and heavy drinking recently have yielded good results. Biomonitoring devices already are valuable tools and with further improvements may become even more useful in both research and practical applications. PMID- 26259000 TI - Electronic Feedback in College Student Drinking Prevention and Intervention. AB - Alcohol consumption is prevalent among college students and can be associated with serious negative consequences. Several efficacious programs using one-on-one brief intervention techniques have been developed to target high-risk drinking by individual students, such as the Brief Alcohol Screening and Intervention for College Students (BASICS) (Dimeff et al. 1999). To reach a larger population (e.g., the incoming freshman class), researchers have adapted these interventions so that students can access them via the Internet or in some other electronic format.The purpose of this review is to discuss specific alcohol intervention programs that were (1) designed to be delivered remotely (e.g., via the Web or on an electronic device) without interaction with a provider and (2) were tested among college students using a randomized controlled trial design. Specific studies were drawn from earlier reviews as well as a comprehensive literature search. Although many programs have limited research support, and some findings are mixed, components that were directly translated from in-person BASICS to remote-delivery mediums (i.e., personalized feedback interventions [PFIs], personalized normative feedback [PNF] interventions), and broader programs that incorporate PFI/ PNF, show promise in reducing alcohol use and/or negative consequences. However, more research is needed and suggestions for how the field can move these interventions forward are discussed. PMID- 26259001 TI - Putting the Screen in Screening: Technology-Based Alcohol Screening and Brief Interventions in Medical Settings. AB - Alcohol is strongly linked to the leading causes of adolescent and adult mortality and health problems, making medical settings such as primary care and emergency departments important venues for addressing alcohol use. Extensive research evidence supports the effectiveness of alcohol screening and brief interventions (SBIs) in medical settings, but this valuable strategy remains underused, with medical staff citing lack of time and training as major implementation barriers. Technology-based tools may offer a way to improve efficiency and quality of SBI delivery in such settings. This review describes the latest research examining the feasibility and efficacy of computer- or other technology-based alcohol SBI tools in medical settings, as they relate to the following three patient populations: adults (18 years or older); pregnant women; and adolescents (17 years or younger).The small but growing evidence base generally shows strong feasibility and acceptability of technology-based SBI in medical settings. However, evidence for effectiveness in changing alcohol use is limited in this young field. PMID- 26259002 TI - Enhancing the Use of Vehicle Alcohol Interlocks With Emerging Technology. AB - Among the earliest applications of health technologies to a safety program was the development of blood alcohol content (BAC) tests for use in impaired-driving enforcement. This led to the development of miniature, highly accurate devices that officers could carry in their pockets. A natural extension of this technology was the vehicle alcohol interlock, which is used to reduce recidivism among drivers convicted of driving under the influence (DUI) by requiring them to install the devices (which will not allow someone with a positive BAC to drive) on their vehicles. While on the vehicle, interlocks have been shown to reduce recidivism by two-thirds. Use of these devices has been growing at the rate of 10 to 15 percent a year, and there currently are more than 300,000 units in use. This expansion in the application of interlocks has benefited from the integration of other emerging technologies into interlock systems. Such technologies include data systems that record both driver actions and vehicle responses, miniature cameras and face recognition to identify the user, Wi-Fi systems to provide rapid reporting on offender performance and any attempt to circumvent the device, GPS tracking of the vehicle, and more rapid means for monitoring the integrity of the interlock system. This article describes how these health technologies are being applied in interlock programs and the outlook for new technologies and new court sanctioning programs that may influence the growth in the use of interlocks in the future. PMID- 26259003 TI - Influence of Social Media on Alcohol Use in Adolescents and Young Adults. AB - Participation in online social media Web sites (e.g., Facebook and Twitter) has skyrocketed in recent years and created a new environment in which adolescents and young adults may be exposed to and influenced by alcohol-related content. Thus, young people are exposed to and display pro-alcohol messages and images through online portrayals of drinking on personal pages as well as unregulated alcohol marketing on social media sites that may reach underage people. Such online displays of alcohol behavior have been correlated with offline alcohol behavior and risky drinking. Health behavior theories have been used to describe the influence of social media sites, including Social Learning Theory, the Media Practice Model, and a more recent conceptual approach called the Facebook Influence Model. Researchers are beginning to assess the potential of social media sites in identifying high-risk drinkers through online display patterns as well as delivering prevention messages and interventions. Future studies need to further expand existing observational work to better understand the role of social media in shaping alcohol-related behaviors and fully exploit the potential of these media for alcohol-related interventions. PMID- 26259004 TI - Ecological Momentary Assessment and Alcohol Use Disorder Treatment. AB - The ability to capture real-time data on human behavior inexpensively, efficiently, and accurately holds promise to transform and broaden our understanding of many areas of health science. One approach to acquiring this type of real-time data is ecological momentary assessment (EMA).This method has been used to collect data in many domains of addiction research, including research on the treatment of alcohol use disorders (AUDs). Empirical evidence supports the hypothesis that use of EMA can improve the quality of AUD treatment research when compared with standard assessment methods because it provides more accurate reporting, allows investigators to examine the dynamic unfolding of the behavior change process at an individual level, and can be used to augment and improve clinical assessment and treatment. Overall, the existing literature provides strong support for the advantages of EMA when combined with standard assessment of addictive behaviors in general. Nevertheless, use of EMA in AUD treatment research thus far has been limited, especially in the area of research on mechanisms of behavior change. Existing research indicates, however, that EMA can be used to deliver tailored feed- back as a novel and potentially transformative approach to improving AUD treatment. This research area clearly warrants additional future efforts. PMID- 26259005 TI - Mobile Delivery of Treatment for Alcohol Use Disorders: A Review of the Literature. AB - Several systems for treating alcohol-use disorders (AUDs) exist that operate on mobile phones. These systems are categorized into four groups: text-messaging monitoring and reminder systems, text-messaging intervention systems, comprehensive recovery management systems, and game-based systems. Text-messaging monitoring and reminder systems deliver reminders and prompt reporting of alcohol consumption, enabling continuous monitoring of alcohol use. Text-messaging intervention systems additionally deliver text messages designed to promote abstinence and recovery. Comprehensive recovery management systems use the capabilities of smart-phones to provide a variety of tools and services that can be tailored to individuals, including in-the-moment assessments and access to peer discussion groups. Game-based systems engage the user using video games. Although many commercial applications for treatment of AUDs exist, few (if any) have empirical evidence of effectiveness. The available evidence suggests that although texting-based applications may have beneficial effects, they are probably insufficient as interventions for AUDs. Comprehensive recovery management systems have the strongest theoretical base and have yielded the strongest and longest-lasting effects, but challenges remain, including cost, understanding which features account for effects, and keeping up with technological advances. PMID- 26259006 TI - Computerized Working-Memory Training as a Candidate Adjunctive Treatment for Addiction. AB - Alcohol and other drug dependencies are, in part, characterized by deficits in executive functioning, including working memory. Working-memory training is a candidate computerized adjunctive intervention for the treatment of alcoholism and other drug dependencies. This article reviews emerging evidence for computerized working memory training as an efficacious adjunctive treatment for drug dependence and highlights future challenges and opportunities in the field of working-memory training, including duration of training needed, persistence of improvements and utility of booster sessions, and selection of patients based on degree of deficits. PMID- 26259007 TI - Computerized Cognitive-Behavioral Therapy. PMID- 26259009 TI - Privacy and Security in Mobile Health (mHealth) Research. AB - Research on the use of mobile technologies for alcohol use problems is a developing field. Rapid technological advances in mobile health (or mHealth) research generate both opportunities and challenges, including how to create scalable systems capable of collecting unprecedented amounts of data and conducting interventions-some in real time-while at the same time protecting the privacy and safety of research participants. Although the research literature in this area is sparse, lessons can be borrowed from other communities, such as cybersecurity or Internet security, which offer many techniques to reduce the potential risk of data breaches or tampering in mHealth. More research into measures to minimize risk to privacy and security effectively in mHealth is needed. Even so, progress in mHealth research should not stop while the field waits for perfect solutions. PMID- 26259008 TI - The Promises and Pitfalls of Digital Technology in Its Application to Alcohol Treatment. AB - Individuals seeking to change their alcohol use form a heterogeneous group with varied treatment goals-including moderation and abstinence-that therefore requires flexible treatment options. The availability of alcohol in the United States, and the pervasive social pressure to drink, warrant treatments that support individuals outside the treatment environment and that foster coping and self-regulation in the face of these demands. Emerging digital technologies show promise for helping both to hone therapies to clients' individual needs and to support clients in settings beyond the clinic. In the broader health care arena, digital health technologies (DHTs) are transforming how health professionals assess, prevent, and treat both physical and mental health problems. DHTs include assessments and interventions delivered via computer, Internet, mobile phone, and wireless or wearable device technologies. The emerging literature examining within-treatment and mobile DHTs highlights an opportunity to create personalized alcohol treatments for every person seeking care. Despite the promises DHTs may hold, however, there still are many potential risks to using them and a number of challenges regarding how to integrate them into treatment successfully. This article will review the current and potential advantages of DHTs in alcohol treatment and the technological, personal, organizational, and systemic limitations of integrating various technology-based assessment and intervention programs into care. PMID- 26259010 TI - Intensifying the Focus on the Contribution of the Inanimate Environment to Health Care-Associated Infections. PMID- 26259011 TI - Associations of life course socioeconomic position and job stress with carotid intima-media thickness. The Brazilian Longitudinal Study of Adult Health (ELSA Brasil). AB - RATIONALE: The association between life course socioeconomic position (SEP) and subclinical atherosclerosis is not consistent across studies. Socioeconomic adversities early in life are related to an increased probability of a low occupational grade and more stressful jobs in adulthood. However, the role of job stress in explaining the life course social gradient in subclinical atherosclerosis is unknown. OBJECTIVES: To examine whether life course SEP is associated with carotid intima-media thickness (IMT) and to investigate whether this association is partially mediated by job stress. METHODS: This study used baseline data (2008-2010) for 8806 current workers from ELSA-Brasil. Maternal education, social class of first occupation and social class of current occupation were used to evaluate childhood, youth and adulthood SEP, respectively. Accumulation of risk across the life course was also evaluated. Job stress was assessed by the Swedish Demand-Control-Support Questionnaire. Directed acyclic graph and linear regression models were used. RESULTS: Low childhood SEP was associated with increased IMT only in women, but low youth and adulthood SEP were associated with higher IMT in both genders. The simultaneous adjustment for all SEP indicators showed that only adulthood SEP continued to be associated with IMT. However, higher IMT values were observed among men and women sequentially exposed to low SEP in more than one period of life. High-strain jobs and low job control were not associated with IMT independent of SEP. CONCLUSION: Our results support a model of the cumulative effects of exposures to SEP across the life span because the highest IMT values were observed in individuals sequentially exposed to low SEP in more than one period of life. We did not find that job stress explained the association between life course SEP and IMT, suggesting that strategies to address socioeconomic inequalities in CVD should target additional steps beyond reducing job stress. PMID- 26259012 TI - Research on health inequalities: A bibliometric analysis (1966-2014). AB - The objective of this study is to report on research production and publications on health inequalities through a bibliometric analysis covering publications from 1966 to 2014 and a content analysis of the 25 most-cited papers. A database of 49,294 references was compiled from the search engine Web of Science. The first article appears in 1966 and deals with equality and civil rights in the United States and the elimination of racial discrimination in access to medical care. By 2003, the term disparity has gained in prominence relative to the term inequality which was initially elected by the researchers. Marmot's 1991 article is one of the five papers with the largest number of citations and contributes to the central perspective of social determinants of health and the British influence on the international status of research on social inequalities of health. PMID- 26259013 TI - Gas Separation Membranes Derived from High-Performance Immiscible Polymer Blends Compatibilized with Small Molecules. AB - An immiscible polymer blend comprised of high-performance copolyimide 6FDA DAM:DABA(3:2) (6FDD) and polybenzimidazole (PBI) was compatibilized using 2 methylimidazole (2-MI), a commercially available small molecule. Membranes were fabricated from blends of 6FDD:PBI (50:50) with and without 2-MI for H2/CO2 separations. The membranes demonstrated a matrix-droplet type microstructure as evident with scanning electron microscopy (SEM) imaging where 6FDD is the dispersed phase and PBI is the continuous phase. In addition, membranes with 2-MI demonstrated a uniform microstructure as observed by smaller and more uniformly dispersed 6FDD domains in contrast to 6FDD:PBI (50:50) blend membranes without 2 MI. This compatibilization effect of 2-MI was attributed to interfacial localization of 2-MI that lowers the interfacial energy similar to a surfactant. Upon the incorporation of 2-MI, the H2/CO2 selectivity improved remarkably, compared to the pure blend, and surpassed the Robeson's upper bound. To our knowledge, this is the first report of the use of a small molecule to compatibilize a high-performance immiscible polymer blend. This approach could afford a novel class of membranes in which immiscible polymer blends can be compatibilized in an economical and convenient fashion. PMID- 26259015 TI - Joint Reconstruction of Multiple Images and Motion in MRI: Application to Free Breathing Myocardial T2Quantification. AB - Exploiting redundancies between multiple images of an MRI examination can be formalized as the joint reconstruction of these images. The anatomy is preserved indeed so that specific constraints can be implemented (e.g. most of the features or spatial gradients should be in the same place in all these images) and only the contrast changes from one image to another need to be encoded. The application of this concept is particularly challenging in cardiovascular and body imaging due to the complex organ deformations, especially with the patient breathing. In this study a joint optimization framework is proposed for reconstructing multiple MR images together with a nonrigid motion model. The motion model takes into account both intra-image and inter-image motion and therefore can correct for most ghosting/blurring artifacts and misregistration between images. The framework was validated with free-breathing myocardial T2 mapping experiments from nine heart transplant patients at 1.5 T. Results showed improved image quality and excellent image alignment with the multi-image reconstruction compared to the independent reconstruction of each image. Segment wise myocardial T2 values were in good agreement with the reference values obtained from multiple breath-holds (62.5 +/- 11.1 ms against 62.2 +/- 11.2 ms which was not significant with p=0.49). PMID- 26259014 TI - Single session imaging of cerebellum at 7 Tesla: obtaining structure and function of multiple motor subsystems in individual subjects. AB - The recent increase in the use of high field MR systems is accompanied by a demand for acquisition techniques and coil systems that can take advantage of increased power and accuracy without being susceptible to increased noise. Physical location and anatomical complexity of targeted regions must be considered when attempting to image deeper structures with small nuclei and/or complex cytoarchitechtonics (i.e. small microvasculature and deep nuclei), such as the brainstem and the cerebellum (Cb). Once these obstacles are overcome, the concomitant increase in signal strength at higher field strength should allow for faster acquisition of MR images. Here we show that it is technically feasible to quickly and accurately detect blood oxygen level dependent (BOLD) signal changes and obtain anatomical images of Cb at high spatial resolutions in individual subjects at 7 Tesla in a single one-hour session. Images were obtained using two high-density multi-element surface coils (32 channels in total) placed beneath the head at the level of Cb, two channel transmission, and three-dimensional sensitivity encoded (3D, SENSE) acquisitions to investigate sensorimotor activations in Cb. Two classic sensorimotor tasks were used to detect Cb activations. BOLD signal changes during motor activity resulted in concentrated clusters of activity within the Cb lobules associated with each task, observed consistently and independently in each subject: Oculomotor vermis (VI/VII) and CrusI/II for pro- and anti-saccades; ipsilateral hemispheres IV-VI for finger tapping; and topographical separation of eye- and hand- activations in hemispheres VI and VIIb/VIII. Though fast temporal resolution was not attempted here, these functional patches of highly specific BOLD signal changes may reflect small-scale shunting of blood in the microvasculature of Cb. The observed improvements in acquisition time and signal detection are ideal for individualized investigations such as differentiation of functional zones prior to surgery. PMID- 26259016 TI - Transport on Riemannian Manifold for Connectivity-Based Brain Decoding. AB - There is a recent interest in using functional magnetic resonance imaging (fMRI) for decoding more naturalistic, cognitive states, in which subjects perform various tasks in a continuous, self-directed manner. In this setting, the set of brain volumes over the entire task duration is usually taken as a single sample with connectivity estimates, such as Pearson's correlation, employed as features. Since covariance matrices live on the positive semidefinite cone, their elements are inherently inter-related. The assumption of uncorrelated features implicit in most classifier learning algorithms is thus violated. Coupled with the usual small sample sizes, the generalizability of the learned classifiers is limited, and the identification of significant brain connections from the classifier weights is nontrivial. In this paper, we present a Riemannian approach for connectivity-based brain decoding. The core idea is to project the covariance estimates onto a common tangent space to reduce the statistical dependencies between their elements. For this, we propose a matrix whitening transport, and compare it against parallel transport implemented via the Schild's ladder algorithm. To validate our classification approach, we apply it to fMRI data acquired from twenty four subjects during four continuous, self-driven tasks. We show that our approach provides significantly higher classification accuracy than directly using Pearson's correlation and its regularized variants as features. To facilitate result interpretation, we further propose a non-parametric scheme that combines bootstrapping and permutation testing for identifying significantly discriminative brain connections from the classifier weights. Using this scheme, a number of neuro-anatomically meaningful connections are detected, whereas no significant connections are found with pure permutation testing. PMID- 26259017 TI - Maximum-Likelihood Joint Image Reconstruction/Motion Estimation in Attenuation Corrected Respiratory Gated PET/CT Using a Single Attenuation Map. AB - This work provides an insight into positron emission tomography (PET) joint image reconstruction/motion estimation (JRM) by maximization of the likelihood, where the probabilistic model accounts for warped attenuation. Our analysis shows that maximum-likelihood (ML) JRM returns the same reconstructed gates for any attenuation map (MU-map) that is a deformation of a given MU-map, regardless of its alignment with the PET gates. We derived a joint optimization algorithm accordingly, and applied it to simulated and patient gated PET data. We first evaluated the proposed algorithm on simulations of respiratory gated PET/CT data based on the XCAT phantom. Our results show that independently of which MU-map is used as input to JRM: (i) the warped MU-maps correspond to the gated MU-maps, (ii) JRM outperforms the traditional post-registration reconstruction and consolidation (PRRC) for hot lesion quantification and (iii) reconstructed gated PET images are similar to those obtained with gated MU-maps. This suggests that a breath-held MU-map can be used. We then applied JRM on patient data with a MU-map derived from a breath-held high resolution CT (HRCT), and compared the results with PRRC, where each reconstructed PET image was obtained with a corresponding cine-CT gated MU-map. Results show that JRM with breath-held HRCT achieves similar reconstruction to that using PRRC with cine-CT. This suggests a practical low-dose solution for implementation of motion-corrected respiratory gated PET/CT. PMID- 26259019 TI - The Influence of Selected Fingerprint Enhancement Techniques on Forensic DNA Typing of Epithelial Cells Deposited on Porous Surfaces. AB - Fingerprints deposited at crime scene can be a source of DNA. Previous reports on the effects of fingerprint enhancement methods have focused mainly on fingermarks deposited in blood or saliva. Here, we evaluate the effects of fingerprint enhancement methods on fingerprints deposited on porous surfaces. We performed real-time quantification and STR typing, the results of which indicated that two methods (iodine fuming and 1,2-indanedione in ethyl acetate enhancement) had no effect on the quantity of DNA isolated and resultant STR alleles when compared to control samples. DNA quantities and allele numbers were lower for samples enhanced with silver nitrate and 1,2-indanedione in acetic acid when compared to control samples. Based on DNA quantity, quality, and observable stochastic effects, our data indicated that iodine fuming and 1,2-indanedione in ethyl acetate were the preferred options for the enhancement of fingerprints on porous surfaces. PMID- 26259018 TI - Examining the Impact of Prior Models in Transmural Electrophysiological Imaging: A Hierarchical Multiple-Model Bayesian Approach. AB - Noninvasive cardiac electrophysiological (EP) imaging aims to mathematically reconstruct the spatiotemporal dynamics of cardiac sources from body-surface electrocardiographic (ECG) data. This ill-posed problem is often regularized by a fixed constraining model. However, a fixed-model approach enforces the source distribution to follow a pre-assumed structure that does not always match the varying spatiotemporal distribution of actual sources. To understand the model data relation and examine the impact of prior models, we present a multiple-model approach for volumetric cardiac EP imaging where multiple prior models are included and automatically picked by the available ECG data. Multiple models are incorporated as an Lp-norm prior for sources, where p is an unknown hyperparameter with a prior uniform distribution. To examine how different combinations of models may be favored by different measurement data, the posterior distribution of cardiac sources and hyperparameter p is calculated using a Markov Chain Monte Carlo (MCMC) technique. The importance of multiple model prior was assessed in two sets of synthetic and real-data experiments, compared to fixed-model priors (using Laplace and Gaussian priors). The results showed that the posterior combination of models (the posterior distribution of p) as determined by the ECG data differed substantially when reconstructing sources with different sizes and structures. While the use of fixed models is best suited in situations where the prior assumption fits the actual source structures, the use of an automatically adaptive set of models may have the ability to better address model-data mismatch and to provide consistent performance in reconstructing sources with different properties. PMID- 26259020 TI - Coordination within medical neighborhoods: Insights from the early experiences of Colorado patient-centered medical homes. AB - BACKGROUND: The term "medical neighborhood" refers to relationships that patient centered medical homes (PCMHs) seek to establish with other providers to facilitate coordinated patient care. Yet, how PCMHs can accomplish this coordination is not well understood. PURPOSE: Drawing upon organizational theory (; ; ), we explored how PCMHs use coordination mechanisms to build and optimize their medical neighborhoods. METHODOLOGY: We used mixed methods, blending data collected via interviews and surveys with practice leaders and care coordinators at 30 months after a PCMH collaborative intervention in Colorado as well as surveys from all providers from 13 PCMHs before and 30 months after the intervention. We used thematic analysis to understand the role and use of coordination mechanisms by PCMHs and changes in the ability to coordinate and deliver care continuity. FINDINGS: PCMHs drew on four coordination mechanisms to build relationships with their medical neighbors: interorganizational routines to improve reliability of information flow; information connectivity to facilitate continuity and safe care; boundary spanners to integrate care across silos; and communication, negotiation, and decision mechanisms to introduce shared accountability. When providers were fairly confident of the patient's diagnosis and management required sequential interactions (such as tests or procedures), PCMHs tended to coordinate care through interorganizational routines and information connectivity. When a diagnosis was less certain and required reciprocal interaction (i.e., consultation), PCMHs employed boundary spanners and communication, negotiation, and decision mechanisms. PRACTICE IMPLICATIONS: Use of coordination mechanisms by PCMHs can help to improve care coordination in medical neighborhoods. All four mechanisms appear to be useful. The optimal mix of coordination mechanisms requires attention to patient context. Successfully building medical neighborhoods also requires meta-leaders, collaboration competencies, and high-quality relationships between providers in primary care, specialty care, and hospitals. PMID- 26259021 TI - Nursing home director of nursing leadership style and director of nursing sensitive survey deficiencies. AB - BACKGROUND: Nursing homes are becoming increasingly complex clinical environments because of rising resident acuity and expansion of postacute services within a context of historically poor quality performance. Discrete quality markers have been linked to director of nursing (DON) leadership behaviors. However, the impact of DON leadership across all measured areas of DON jurisdiction has not been tested using comprehensive domains of quality deficiencies. PURPOSE: The aim of this study was to examine the effects of DON leadership style including behaviors that facilitate the exchange of information between diverse people on care quality domains through the lens of complexity science. METHODOLOGY: Three thousand six hundred nine DONs completed leadership and intent-to-quit surveys. Quality markers that were deemed DON sensitive included all facility survey deficiencies in the domains of resident behaviors/facility practices, quality of life, nursing services, and quality of care. Logistic regression procedures estimated associations between variables. FINDINGS: The odds of deficiencies for all DON sensitive survey domains were lower in facilities where DONs practiced complexity leadership including more staff input and shared decisional authority. DON quit intentions were aligned with higher odds of facility deficiencies across all domains. PRACTICE IMPLICATIONS: Results supported the hypotheses that DONs using complexity leadership approaches by interacting more freely with staff, discussing resident issues, and sharing decision making produced better care outcomes from every DON sensitive metric assessed by Centers for Medicare and Medicaid Services. The mechanism linking poor quality with high DON quit intentions is an area for future research. Encouraging DON use of complexity leadership approaches has the potential to improve a broad swath of quality outcomes. PMID- 26259022 TI - Two sides of the safety coin?: How patient engagement and safety climate jointly affect error occurrence in hospital units. AB - BACKGROUND: Safety climate (SC) and more recently patient engagement (PE) have been identified as potential determinants of patient safety, but conceptual and empirical studies combining both are lacking. PURPOSES: On the basis of extant theories and concepts in safety research, this study investigates the effect of PE in conjunction with SC on perceived error occurrence (pEO) in hospitals, controlling for various staff-, patient-, and hospital-related variables as well as the amount of stress and (lack of) organizational support experienced by staff. Besides the main effects of PE and SC on error occurrence, their interaction is examined, too. METHODOLOGY/APPROACH: In 66 hospital units, 4,345 patients assessed the degree of PE, and 811 staff assessed SC and pEO. PE was measured with a new instrument, capturing its core elements according to a recent literature review: Information Provision (both active and passive) and Activation and Collaboration. SC and pEO were measured with validated German-language questionnaires. Besides standard regression and correlational analyses, partial least squares analysis was employed to model the main and interaction effects of PE and SC on pEO, also controlling for stress and (lack of) support perceived by staff, various staff and patient attributes, and potential single-source bias. FINDINGS: Both PE and SC are associated with lower pEO, to a similar extent. The joint effect of these predictors suggests a substitution rather than mutually reinforcing interaction. Accounting for control variables and/or potential single source bias slightly attenuates some effects without altering the results. PRACTICE IMPLICATIONS: Ignoring PE potentially amounts to forgoing a potential source of additional safety. On the other hand, despite the abovementioned substitution effect and conjectures of SC being inert, PE should not be considered as a replacement for SC. PMID- 26259023 TI - Highly Symmetric Gold Nanostars: Crystallographic Control and Surface-Enhanced Raman Scattering Property. AB - Gold nanostars have attracted widespread interest due to their remarkable properties and broad applications in plasmonics, spectroscopy, biomedicine, and energy conversion. However, current synthetic methods of Au nanostars have limited control over their symmetry; most existing nanostars are characterized by having uncertain number of arms with different lengths and random spatial arrangement. This morphological arbitrariness not only hampers the fundamental understanding of the properties of Au nanostars, but also lead to poor reproducibility in their applications. Here we demonstrate that, by using a robust solution-phase method, Au nanostars with unpreceded degree of symmetry control can be obtained in high yield and with remarkable monodispersity. Icosahedral seeds are used to dictate the growth of 3D evenly distributed arms in an Ih symmetric manner. Alkylamines serve as shape-control agent to regulate the growth of the hexagonal pyramidal arms enclosed by high-index facets. Benefiting from their high symmetry, the Au nanostars exhibit superior single-particle SERS performance compared to asymmetric Au nanostars, in terms of both intensity and reproducibility. PMID- 26259024 TI - Structural elucidation of in vitro metabolites of bavachinin in rat liver microsomes by LC-ESI-MSn and chemical synthesis. AB - 1. Bavachinin isolated from Psoralea corylifolia has various activities, such as antimicrobial, antiallergic, antitumor and so on. Our previous study showed that natural bavachinin exhibits peroxisome proliferator-activated receptor gamma agonist activity. 2. In vitro studies on bavachinin metabolism were conducted using rat liver microsomes incubated at 37 degrees C for 60 min. 3. Structures of eight metabolites of the incubation mixtures were cautiously characterized using electrospray tandem mass spectra and three synthetic compounds. The results indicated that eight metabolites of bavachinin were biotransformed mainly through oxidation. 4. The metabolic pathways of bavachinin were elucidated in vitro. These results contribute to the understanding of bavachinin's in vivo metabolism. PMID- 26259025 TI - The impact of the concentration of drug binding plasma proteins on drug distribution according to Oie-Tozer's model. AB - 1. New equations have been developed from an updated version of Oie-Tozer's model expressing how the free concentration and volume of distribution change in relation to changes in the concentration of drug binding plasma proteins. This updated model accommodates more than one drug binding plasma protein to contribute to the plasma protein binding. 2. Demonstrations of the model show that variability in the concentration of one plasma protein has considerably less impact on the free drug concentration and volume of distribution if other plasma proteins contribute to binding, than if they don't. PMID- 26259026 TI - TM6SF2 rs58542926 is not associated with steatosis and fibrosis in large cohort of patients with genotype 1 chronic hepatitis C. AB - BACKGROUND & AIMS: We tested the putative association of the rs58542926 variant of TM6SF2, a recently described genetic determinant of nonalcoholic fatty liver disease, with steatosis and fibrosis in genotype 1(G1) chronic hepatitis C(CHC) patients. METHODS: A total of 694 consecutively biopsied Caucasian G1 CHC patients were genotyped for TM6SF2 rs58542926, IL28B rs12979860 and PNPLA3 rs738409. Steatosis was classified as absent (<5%), mild-moderate(5-29%) and severe(>=30%), Fibrosis was considered severe if=F3-F4. RESULTS: Carriers of TM6SF2 rs58542926 (6.3% of patients) exhibited lower serum levels of cholesterol (P = 0.04) and triglycerides (P = 0.01), but a similar distribution of steatosis severity (P = 0.63), compared to noncarriers. Prevalence and severity of steatosis were reduced in IL28B C allele carriers (P = 0.005) and elevated in PNPLA3 G allele carriers (P < 0.001). After adjustment for age, gender, body mass index and homoeostasis model assessment score, steatosis severity was independently associated with IL28B rs12979860 (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.55-0.86, P = 0.001) and PNPLA3 rs738409 (OR 1.84, 95% CI 1.46-2.83, P < 0.001), but not TM6SF2 rs58542926 (OR 1.48, 95% CI 0.82-2.69, P = 0.19). Variants of TM6SF2 (30.9% vs. 25%, P = 0.40), IL28B and PNPLA3 were not directly associated with fibrosis severity, although variants of IL28B and PNPLA3 promoted steatosis (OR 1.36, 95% CI 1.06-1.75, P = 0.01) that in turn is associated with severe fibrosis. CONCLUSIONS: In G1 CHC patients, TM6SF2 rs58542926 does not affect the histological severity of liver damage. However, IL28B rs12979860 and PNPLA3 rs738409 modify steatosis. PMID- 26259027 TI - Telemental Health for Children and Adolescents: An Overview of Legal, Regulatory, and Risk Management Issues. AB - OBJECTIVE: The use of technology to provide telemental healthcare continues to increase; however, little has been written about the legal and regulatory issues involved in providing this form of care to children and adolescents. METHODS: This article reviews existing laws and regulations to summarize the risk management issues relevant to providing telemental healthcare to children and adolescents. RESULTS: There are several legal and regulatory areas in which telemental health clinicians need to have awareness. These areas include: 1) Licensure, 2) malpractice liability, 3) credentialing and privileging, 4) informed consent, 5) security and privacy, and 6) emergency management. CONCLUSIONS: Although legal and regulatory challenges remain in providing telemental healthcare to children and adolescents, it is possible to overcome these challenges with knowledge of the issues and appropriate risk management strategies. We provide general knowledge of these key legal and regulatory issues, along with some risk management recommendations. PMID- 26259028 TI - Avocado Proanthocyanidins as a Source of Tyrosinase Inhibitors: Structure Characterization, Inhibitory Activity, and Mechanism. AB - Proanthocyanidins were purified from avocado (Persea americana) fruit, and their structures were analyzed by matrix-assisted laser desorption/ionization-time-of flight mass spectrometry (MALDI-TOF MS) and high-performance liquid chromatography-electrospray ionization-QTRAP mass spectrometry (HPLC-ESI-QTRAP MS) techniques. The results obtained from mass spectrometry (MS) analysis demonstrated that the proanthocyanidins were homo- and heteropolymers of procyanidins, prodelphinidins, propelargonidins, and procyanidin gallate. From the enzyme analysis, the results showed that they could inhibit the monophenolase and diphenolase activities of tyrosinase. The inhibition mechanism of the proanthocyanidins on the enzyme was further studied, and the results indicated that they were reversible and competitive inhibitors. Finally, the results acquired from molecular docking, fluorescence quenching, and copper ion interacting tests revealed that adjacent hydroxyl groups on the B ring of proanthocyanidins could chelate the dicopper catalytic center of the enzyme. In addtion, proanthocyanidins were proven to be an efficient quencher of substrates. This study would lay a scientific foundation for their use in agriculture, food, and nutrition industries. PMID- 26259029 TI - Detection of the optic disc in fundus images by combining probability models. AB - In this paper, we propose a combination method for the automatic detection of the optic disc (OD) in fundus images based on ensembles of individual algorithms. We have studied and adapted some of the state-of-the-art OD detectors and finally organized them into a complex framework in order to maximize the accuracy of the localization of the OD. The detection of the OD can be considered as a single object detection problem. This object can be localized with high accuracy by several algorithms extracting single candidates for the center of the OD and the final location can be defined using a single majority voting rule. To include more information to support the final decision, we can use member algorithms providing more candidates which can be ranked based on the confidence ordered by the algorithms. In this case, a spatial weighted graph is defined where the candidates are considered as its nodes, and the final OD position is determined in terms of finding a maximum-weighted clique. Now, we examine how to apply in our ensemble-based framework all the accessible information supplied by the member algorithms by making them return confidence values for each image pixel. These confidence values inform us about the probability that a given pixel is the center point of the object. We apply axiomatic and Bayesian approaches, as in the case of aggregation of judgments of experts in decision and risk analysis, to combine these confidence values. According to our experimental study, the accuracy of the localization of OD increases further. Besides single localization, this approach can be adapted for the precise detection of the boundary of the OD. Comparative experimental results are also given for several publicly available datasets. PMID- 26259030 TI - Gyrate Atrophy in 2 Siblings - Ophthalmological Findings and A New Mutation. PMID- 26259031 TI - Label-Free real-time quantification of enzyme levels by interferometric spectroscopy combined with gelatin-modified nanoporous anodic alumina photonic films. AB - Herein, we present an interferometric sensor based on the combination of chemically functionalized nanoporous anodic alumina photonic films (NAA-PFs) and reflectometric interference spectroscopy (RIfS) aimed to detect trace levels of enzymes by selective digestion of gelatin. The fabrication and sensing performance of the proposed sensor were characterized in real-time by estimating the changes in effective optical thickness (i.e., sensing principle) of gelatin modified NAA-PFs (i.e., sensing element) during enzymatic digestion. The working range (WR), sensitivity (S), low limit of detection (LLoD), and linearity (R(2)) of this enzymatic sensor were established by a series of experiments with different concentrations of gelatin (i.e., specific chemical sensing element) and trypsin (i.e., analyte), a model protease enzyme with relevant implications as a biomarker in the diagnosis of several diseases. The chemical selectivity of the sensor was demonstrated by comparison of gelatin digestion by other nonspecific enzyme models such as chymotrypsin and horseradish peroxidase. Furthermore, the role of the chemical sensing element (i.e., gelatin) was assessed by using hemoglobin instead of gelatin. Finally, we demonstrated that this sensor can be readily used to establish the kinetic parameters of enzymatic reactions. The obtained results revealed that the presented sensor has a promising potential to be used as a point-of-care system for fast detection of gastrointestinal diseases at early stages. PMID- 26259034 TI - Synthesis of Highly Substituted Quinolines via a Tandem Ynamide Benzannulation/Iodocyclization Strategy. AB - A two-stage "tandem strategy" for the regiocontrolled synthesis of very highly substituted quinolines is described. Benzannulation based on the reaction of cyclobutenones or diazo ketones with N-propargyl-substituted ynamides proceeds via a cascade of several pericyclic reactions to generate multiply substituted aniline derivatives. In the second stage of the tandem strategy, triflate derivatives of the phenolic benzannulation products undergo Larock cyclization upon exposure to iodine to form products that are further elaborated by methods such as palladium-catalyzed coupling to generate quinolines that can be substituted at every position of the bicyclic system. PMID- 26259033 TI - Retrotransposon insertions in the clonal evolution of pancreatic ductal adenocarcinoma. AB - Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed after the disease has metastasized; it is among the most lethal forms of cancer. We recently described aberrant expression of an open reading frame 1 protein, ORF1p, encoded by long interspersed element-1 (LINE-1; L1) retrotransposon, in PDAC. To test whether LINE-1 expression leads to somatic insertions of this mobile DNA, we used a targeted method to sequence LINE-1 insertion sites in matched PDAC and normal samples. We found evidence of 465 somatic LINE-1 insertions in 20 PDAC genomes, which were absent from corresponding normal samples. In cases in which matched normal tissue, primary PDAC and metastatic disease sites were available, insertions were found in primary and metastatic tissues in differing proportions. Two adenocarcinomas secondarily involving the pancreas, but originating in the stomach and duodenum, acquired insertions with a similar discordance between primary and metastatic sites. Together, our findings show that LINE-1 contributes to the genetic evolution of PDAC and suggest that somatic insertions are acquired discontinuously in gastrointestinal neoplasms. PMID- 26259035 TI - Anxiogenic and Stressor Effects of the Hypothalamic Neuropeptide RFRP-3 Are Overcome by the NPFFR Antagonist GJ14. AB - RFamide-related peptide-3 (RFRP-3) is a recently discovered neuropeptide that has been proposed to play a role in the stress response. We aimed to elucidate the role of RFRP-3 and its receptor, neuropeptide FF (NPFF1R), in modulation of stress and anxiety responses. To achieve this, we characterized a new NPFF1R antagonist because our results showed that the only commercially available putative antagonist, RF9, is in fact an agonist at both NPFF1R and the kisspeptin receptor (KISS1R). We report here the identification and pharmacological characterization of GJ14, a true NPFFR antagonist. In in vivo tests of hypothalamic-pituitary-adrenal (HPA) axis function, GJ14 completely blocked RFRP 3-induced corticosterone release and neuronal activation in CRH neurons. Furthermore, chronic infusion of GJ14 led to anxiolytic-like behavior, whereas RFRP-3 infusion had anxiogenic effects. Mice receiving chronic RFRP-3 infusion also had higher basal circulating corticosterone levels. These results indicate a stimulatory action of RFRP-3 on the HPA axis, consistent with the dense expression of NPFF1R in the vicinity of CRH neurons. Importantly, coinfusion of RFRP-3 and GJ14 completely reversed the anxiogenic and HPA axis-stimulatory effects of RFRP-3. Here we have established the role of RFRP-3 as a regulator of stress and anxiety. We also show that GJ14 can reverse the effects of RFRP-3 both in vitro and in vivo. Infusion of GJ14 causes anxiolysis, revealing a novel potential target for treating anxiety disorders. PMID- 26259032 TI - PCSK6-mediated corin activation is essential for normal blood pressure. AB - Hypertension is the most common cardiovascular disease, afflicting >30% of adults. The cause of hypertension in most individuals remains unknown, suggesting that additional contributing factors have yet to be discovered. Corin is a serine protease that activates the natriuretic peptides, thereby regulating blood pressure. It is synthesized as a zymogen that is activated by proteolytic cleavage. CORIN variants and mutations impairing corin activation have been identified in people with hypertension and pre-eclampsia. To date, however, the identity of the protease that activates corin remains elusive. Here we show that proprotein convertase subtilisin/kexin-6 (PCSK6, also named PACE4; ref. 10) cleaves and activates corin. In cultured cells, we found that corin activation was inhibited by inhibitors of PCSK family proteases and by small interfering RNAs blocking PCSK6 expression. Conversely, PCSK6 overexpression enhanced corin activation. In addition, purified PCSK6 cleaved wild-type corin but not the R801A variant that lacks the conserved activation site. Pcsk6-knockout mice developed salt-sensitive hypertension, and corin activation and pro-atrial natriuretic peptide processing activity were undetectable in these mice. Moreover, we found that CORIN variants in individuals with hypertension and pre-eclampsia were defective in PCSK6-mediated activation. We also identified a PCSK6 mutation that impaired corin activation activity in a hypertensive patient. Our results indicate that PCSK6 is the long-sought corin activator and is important for sodium homeostasis and normal blood pressure. PMID- 26259036 TI - General Strategy for Fabricating Sandwich-like Graphene-Based Hybrid Films for Highly Reversible Lithium Storage. AB - We report a general strategy for the fabrication of freestanding sandwich-like graphene-based hybrid films by electrostatic adsorption and following reduction reaction. We demonstrate that by rational control of pH value in precursors, graphene oxide (GO) sheets can form three-dimensional (3D) sandwich frameworks with nanoparticles decorated between the layers of graphene. In our proof-of concept study, we prepared the graphene/Si/graphene (G@Si@G) sandwich-like films. When used as negative electrode materials for lithium-ion batteries, it exhibits superior lithium-ion storage performance (~1800 mA h g(-1) after 40 cycles at 100 mA g(-1)). Importantly, with this simple and general method, we also successfully synthesized graphene/Fe2O3/graphene and graphene/TiO2/graphene hybrid films, showing improved electrochemical performance. The good electrochemical property results from the enhanced electron transport rate, and the 3D flexible matrix to buffer volume changes during cycling. In addition, the porous sandwich structure consisting of plate-like graphene with high surface area provides effective electrolyte infiltration and promotes diffusion rate of Li(+), leading to an improved rate capability. PMID- 26259037 TI - Managing type 2 diabetes in Black patients. AB - Despite many novel treatments available for managing type 2 diabetes mellitus, Black patients continue to disproportionately suffer complications associated with poor glycemic control. This article describes a comprehensive approach to managing diabetes mellitus in these patients while addressing cultural nuances that may be barriers to positive outcomes. PMID- 26259038 TI - Euthanasia in Belgium and the Netherlands: On a Slippery Slope? PMID- 26259039 TI - Barbecue Fumes: An Overlooked Source of Health Hazards in Outdoor Settings? AB - Barbecuing or charcoal-grilling has become part of popular outdoor recreational activities nowadays; however, potential human health hazards through outdoor exposure to barbecue fumes have yet to be adequately quantified. To fill this knowledge gap, atmospheric size-fractioned particle and gaseous samples were collected near an outdoor barbecuing vendor stall (along with charcoal-grilled food items) in Xinjiang of Northwest China with a 10-stage micro-orifice uniform deposit impactor and a polyurethane foam (PUF) sampler and were analyzed for particulate matter and polycyclic aromatic hydrocarbons (PAHs). Exposure to PAHs through inhalation and dermal contact by adult consumers who spent 1 h per day near a charcoal-grilling vendor for a normal meal (lunch or dinner) amounted to a BaP equivalent (BaPeq) dosage of 3.0-77 ng day(-1) (inhalation: 2.8-27 ng day(-1) of BaPeq; dermal contact: 0.2-50 ng day(-1) of BaPeq), comparable to those (22 220 ng day(-1) of BaPeq) from consumer exposure through the consumption of charcoal-grilled meat, assumed to be at the upper limit of 50-150 g. In addition, the potential health risk was in the range of 3.1 * 10(-10) to 1.4 * 10(-4) for people of different age groups with inhalation and dermal contact exposure to PAHs once a day, with a 95% confidence interval (7.2 * 10(-9) to 1.2 * 10(-5)) comparable to the lower limit of the potential cancer risk range (1 * 10(-6) to 1 * 10(-4)). Sensitivity analyses indicated that the area of dermal contact with gaseous contaminants is a critical parameter for risk assessment. These results indicated that outdoor exposure to barbecue fumes (particularly dermal contact) may have become a significant but largely neglected source of health hazards to the general population and should be well-recognized. PMID- 26259040 TI - Not Again: Benzodiazepines Once More Under Attack. PMID- 26259041 TI - Silybin and 2,3-Dehydrosilybin Flavonolignans as Free Radical Scavengers. AB - The electronic properties of six derivatives of silybin (characterized by the absence of the 2,3 double bond) and six derivatives of 2,3-dehydrosilybin (characterized by the presence of the 2,3 double bond) have been studied by applying density functional theory to fully understand the free radical scavenger's mechanism for action and the relationship between reactivity and chemical structure. Optimized geometries, Raman spectra, and lambdamax values are reported, enabling us to characterize the systems. These spectra may be useful for monitoring the oxidation between silybin and 2,3-dehydrosilybin, thus providing important experimental information. The relative abundance of deprotonated species under physiological conditions is also reported. Under physiological conditions (pH 7.4), ~70% of silybin is protonated, but 60% of 2,3 dehydrosilybin is deprotonated. The free radical scavenger capacity is analyzed in terms of two mechanisms: electron transfer and adduct formation. Deprotonated molecules are better electron donors and worse electron acceptors than non deprotonated species. The conclusions derived from this investigation completely concur with previous experimental results. The free radical scavenging activity of 2,3-dehydrosilybin derivatives is higher than that for silybin derivatives. What was not previously considered was the importance of the deprotonated species, which is remarkable and may be important for future experiments. PMID- 26259042 TI - Sport participation, screen time, and personality trait development during childhood. AB - This investigation explored the contribution of extracurricular sport and screen time viewing (television viewing and electronic gaming) to personality trait stability and change during childhood. Two independent samples of 3,956 young children (age 6) and 3,862 older children (age 10) were taken from the Longitudinal Study of Australian Children. Parent-reported child sport participation, screen time, and personality traits were measured at baseline and again 24 months later. Young children who were more active recorded more of a decrease in introversion, less of a decrease in persistence, and less of an increase in reactivity, than those who were less active. Older children who were more active recorded less of an increase in introversion and more of an increase in persistence than those who were less active. In addition, young children who continued participation in extracurricular sport had greater intra-individual stability of personality for introversion. These finding suggest that an active lifestyle might help to facilitate desirable personality trait stability and change during childhood. PMID- 26259043 TI - Syndecan-1 up-regulates microRNA-331-3p and mediates epithelial-to-mesenchymal transition in prostate cancer. AB - MicroRNAs (miRNAs) are small noncoding RNAs with a length of approximately 19-24 nucleotides that regulate gene expression through translational inhibition and contribute to the progression of various tumors including prostate cancer. Aberrant expression of miRNAs has been implicated in the progression and metastasis of prostate cancer. The present study aimed to investigate whether miR 331-3p controlled by syndecan-1 positively affects the epithelial-to-mesenchymal transition (EMT). Overexpression of miR-331-3p upregulated mesenchymal markers such as vimentin, N-cadherin, and snail and downregulated epithelial markers such as E-cadherin and desmoplakin in the prostate cancer cell line PC3. We identified Neuropilin 2 and nucleus accumbens-associated protein 1 as putative target molecules in silico, as they were closely associated with the expression of miR 331-3p and TGF-beta/Smad 4 signals. In situ hybridization and immunohistochemistry of radical prostatectomy samples revealed miR-331-3p in cancer cells with high Gleason patterns, in which EMT was demonstrated by decreased E-cadherin, and increased vimentin staining. Syndecan-1 gene silencing decreased levels of Dicer, which is involved in miRNA maturation. MiR-331-3p mediated miRNA maturation and enhanced EMT via effects on TGF-beta/Smad 4 and Dicer are essential for the development of prostate cancer mediated by syndecan 1. (c) 2015 Wiley Periodicals, Inc. PMID- 26259044 TI - Sensitive Detection of a Modified Base in Single-Stranded DNA by a Single-Walled Carbon Nanotube. AB - In this work, we use molecular dynamics simulations to study the responses of the configuration of single-strand DNA (ssDNA) within a carbon nanotube (CNT) and the concomitant ion flow to a single modified base, i.e., benzoimidazole (Bzim) modified 5-hydroxymethyl cytosine (5hmC). Our simulation results show the Bzim modified 5hmC can considerably increase the ion flow through a single-walled carbon nanotube (SWCNT), despite its larger size, which is consistent with prior experimental results. This phenomenon is attributed to enhanced adsorption of DNA to the interior wall of the CNT driven by the Bzim-modified 5hmC, leading to a reduced steric effect on ion transport through the CNT. As revealed in this work, the distribution of ssDNA can be affected by limited change in the interactions with the CNT surface. Such behavior of ssDNA within small-sized CNTs can be exploited to further improve the sensitivity of nanopore detection. PMID- 26259045 TI - "Stainless" Gold Nanorods: Preserving Shape, Optical Properties, and SERS Activity in Oxidative Environment. AB - One of the main limitations to the application of gold nanorods (Au NRs) as surface-enhanced Raman scattering (SERS) probes for in situ monitoring of chemical processes is their instability in oxidative environments. Oxidation induces progressive anisotropic shortening of the NRs, which are eventually dissolved once this process has been completed. This paper compares two types of Au NRs, obtained through different routes and characterized by similar aspect ratios but different sizes. The key factors influencing the resistance of Au NRs to oxidation were systematically investigated, showing that the reduction of free bromide species and the increase of the particle size allowed the NRs to maintain their stability under harsh environments for several weeks. The most stable Au NRs were also demonstrated to be highly efficient SERS substrates in a series of Raman experiments involving molecular probes, treated under either oxidizing or nonoxidizing conditions, which simulate the oxidation of organic pollutants in water. These hallmarks make these "stainless" Au NRs attractive tools for ultrasensitive diagnostic under real working conditions. PMID- 26259046 TI - Imaging of the Sclera in Patients with Scleritis and Episcleritis using Anterior Segment Optical Coherence Tomography. AB - PURPOSE: To evaluate the sclera and episclera in patients with scleritis and episcleritis using anterior segment optical coherence tomography (AS-OCT). METHODS: Cross-sectional prospective case series of 11 consecutive patients with episcleral or scleral inflammatory disease located anterior to the equator. The thickness of the ocular wall (sclera and the episclera) was measured using AS-OCT and compared to the contralateral healthy eye. RESULTS: Eleven patients with a mean age of 49.5 years presented with symptomatic scleritis or episcleritis. The mean thickness of the ocular wall in the affected eye was 982 +/- 56 MUm compared to 790 +/- 23 MUm (p < 0.05) in the fellow eye. Enhanced-depth AS-OCT showed that the thickening occurred mainly in the episcleral layer in both scleritis and episcleritis. CONCLUSION: Enhanced-depth AS-OCT may be a useful tool for imaging scleritis or episcleritis and may serve to monitor therapeutic success in these patients. PMID- 26259047 TI - Postoperative Leukocytosis After Robotic-Assisted Radical Prostatectomy Is Not Associated with Perioperative Outcome and Histopathological Findings. AB - INTRODUCTION: Recently a retrospective study has been published describing a significant correlation of immediate postoperative leukocytosis (IPLC) and a favorable pathological Gleason score (pGS) in patients undergoing robotic assisted radical prostatectomy (RARP). The aim of the present study was to prospectively validate these results on an external dataset. MATERIALS AND METHODS: In total, 346 patients undergoing RARP as first-line therapy for localized prostate cancer were included. Clinical and histopathological parameters, criteria of IPLC, and pGS were recorded prospectively. Potential association between IPLC and pGS was evaluated by univariate and multivariate analyses. RESULTS: IPLC was found in 77.2% (n = 267) of all patients with a median leukocyte blood count (LBC) of 12.5 * 10(9)/L (interquartile range, 10.2 15 * 10(9)/L). Of these, in 255 patients IPLC was found within the range of 10-20 * 10(9)/L, whereas an IPLC of >20 * 10(9)/L was found in only 12 patients. Of the patients, 49.1%, 40.5%, and 10.4% presented with a pGS6, pGS7, and pGS8-10 tumor, respectively. There was neither a univariate nor a multivariate correlation between IPLC and pGS. Furthermore, no significant correlation could be detected between IPLC and other clinical, intraoperative, or histopathological criteria. In 175 (66%) patients with IPLC normal LBC levels were measured on postoperative Day 4. CONCLUSIONS: IPLC was not associated with more favorable tumor biology (lower pGS, better tumor stage) and not influenced by patient conditions (age, body mass index, American Society of Anesthesiologists score, smoking) or intraoperative parameters (blood loss, operating time, surgeon). In addition, there was no significant correlation with serious complications (Clavien-Dindo Grade 3a/b) within a period of 90 days. PMID- 26259049 TI - Ambient air pollution, blood mitochondrial DNA copy number and telomere length in a panel of diabetes patients. AB - CONTEXT: Several previous studies proposed a link between particulate matter (PM) pollution and mitochondrial DNA copy number (MtDNAcn) and telomere length (TL). However, this evidence is quite limited and inconsistent, especially on how the particle size affects the associations and on whether there exists such an association with gaseous pollutants. OBJECTIVE: We aimed to investigate the short term associations of size-fractionated PM and gaseous pollutants with blood MtDNAcn and TL. METHODS: We conducted a longitudinal panel study involving 6 repeated measurements among 35 Type 2 diabetes patients in Shanghai, China from April to June 2013. We measured the real-time concentrations of size-fractionated PM (0.25-10 MUm) and criteria gaseous pollutants. Blood MtDNAcn and TL were tested by a quantitative real-time PCR-based assay. Linear mixed-effect models were used to explore their short-term associations using multiple lag periods, after controlling for individual characteristics, time trends and weather conditions. RESULTS: In general, there were inverse but statistically non significant associations between all pollutants and MtDNAcn. Coarse PM appeared to be more closely linked with MtDNAcn than smaller PM. The associations between various air pollutants and TL were generally positive but very weak. There were no clear lag patterns for these associations. The associations between air pollutants and MtDNAcn and TL were strengthened but still not significant among those who did not take statins regularly. CONCLUSIONS: This study did not support short-term associations of PM or gaseous pollutants with blood MtDNAcn and TL in type 2 diabetes patients. PMID- 26259048 TI - Pharmacological treatments for preventing epilepsy following traumatic head injury. AB - BACKGROUND: Head injury is a common event and can cause a spectrum of motor and cognition disabilities. A frequent complication is seizures. Antiepileptic drugs (AED) such as phenytoin are often used in clinical practice with the hopes of preventing post-traumatic epilepsy. Whether immediate medical intervention following head trauma with either AEDs or neuroprotective drugs can alter the process of epileptogenesis and lead to a more favorable outcome is currently unknown. This review attempted to address the effectiveness of these treatment interventions. This review updates and expands on the earlier Cochrane review. OBJECTIVES: To compare the efficacy of antiepileptic drugs and neuroprotective agents with placebo, usual care or other pharmacologic agents for the prevention of post-traumatic epilepsy in people diagnosed with any severity of traumatic brain injury. SEARCH METHODS: We searched The Cochrane Epilepsy Group's specialized register, CENTRAL, MEDLINE, ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform (ICTRP) in January 2015. We searched EMBASE, Biological Abstracts and National Research Register in September 2014 and SCOPUS in December 2013. The Cochrane Epilepsy Group performed handsearches of relevant journals. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that include AEDs or neuroprotective agents compared with placebo, another pharmacologic agent or a usual care group. The outcomes measured included a seizure occurring within one week of trauma (early seizure), seizure occurring later than one week post-trauma (late seizure), mortality and any adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study quality and extracted the data. We calculated risk ratios (RR) and 95% confidence intervals (CI) for each outcome. We used random effects models in the meta-analyses and performed pre-defined subgroup and sensitivity analyses. MAIN RESULTS: This review included 10 RCTs (reported in 12 articles) consisting of 2326 participants The methodological quality of the studies varied. The type of intervention was separated into three categories; AED versus placebo or standard care, alternative neuroprotective agent versus placebo or standard care and AED versus other AED. Treatment with an AED (phenytoin or carbamazepine) decreased the risk of early seizure compared with placebo or standard care (RR 0.42, 95% CI 0.23 to 0.73; very low quality evidence). There was no evidence of a difference in the risk of late seizure occurrence between AEDs and placebo or standard care (RR 0.91, 95% CI 0.57 to 1.46; very low quality evidence). There was no evidence of a significant difference in all-cause mortality between AEDs and placebo or standard care (RR 1.08 95% CI 0.79 to 1.46,very low quality of evidence). Only one study looked at other potentially neuroprotective agents (magnesium sulfate) compared with placebo. The risk ratios were: late seizure 1.07 (95% CI 0.53 to 2.17) and all-cause mortality 1.20 (95% CI 0.80 to 1.81). The risk ratio for occurrence of early seizure was not estimable.Two studies looked at comparison of two AEDs (levetiracetam, valproate) with phenytoin used as the main comparator in each study. The risk ratio for all cause mortality was 0.53 (95% CI 0.30 to 0.94). There was no evidence of treatment benefit of phenytoin compared with another AED for early seizures (RR 0.66, 95% 0.20 to 2.12) or late seizures(RR 0.77, 95% CI 0.46 to 1.30).Only two studies reported adverse events. The RR of any adverse event with AED compared with placebo was 1.65 (95% CI 0.73 to 3.66; low quality evidence). There were insufficient data on adverse events in the other treatment comparisons. AUTHORS' CONCLUSIONS: This review found low-quality evidence that early treatment with an AED compared with placebo or standard care reduced the risk of early post traumatic seizures. There was no evidence to support a reduction in the risk of late seizures or mortality. There was insufficient evidence to make any conclusions regarding the effectiveness or safety of other neuroprotective agents compared with placebo or for the comparison of phenytoin, a traditional AED, with another AED. PMID- 26259050 TI - Disseminated Favus Caused by Microsporum gypseum in a Patient with Systemic Lupus Erythematosus. PMID- 26259051 TI - Performance-Based Versus Self-Reported Outcomes Using the Hip Disability and Osteoarthritis Outcome Score After Total Hip Arthroplasty. AB - OBJECTIVE: The purpose of this study was to explore the relationship between patients' self-reported and performance-based function after total hip arthroplasty (THA). DESIGN: Twenty-three patients (age, 61.4 +/- 8.3 yrs) undergoing primary THA for hip osteoarthritis participated. Self-reported function and recovery was measured using the Hip Disability and Osteoarthritis Outcome Score activities of daily living and pain subscales. Performance-based functional measures included the timed up and go test, the stair climbing test, and the 6-minute walk test. Outcome measures were assessed preoperatively and postoperatively at 1 and 6 mos. RESULTS: One month after THA, performance-based function declined compared with baseline as follows: timed up and go test, -22.1% +/- 25.4%; stair climbing test, -58.5% +/- 63.6%; and 6-minute walk test, -22.6% +/- 31.7%. In contrast, self-reported function on the Hip Disability and Osteoarthritis Outcome Score Activities of Daily Living significantly improved 1 mo after THA compared with baseline: 40.8% +/- 33.3%. One to 6 mos after THA, there were significant improvements in timed up and go test, stair climbing test, and 6-minute walk test, which paralleled improvements on the Hip Disability and Osteoarthritis Outcome Score subscales, although changes were not significantly correlated. CONCLUSION: The disparity between changes in Hip Disability and Osteoarthritis Outcome Scores and functional performance postoperatively suggests that patients may overestimate their functional capacity early after THA, likely in response to pain improvements over the same time period. Therefore, outcomes assessment after THA should include both self-report and performance-based functional measures. PMID- 26259052 TI - Active-Arm Passive-Leg Exercise Improves Cardiovascular Function in Spinal Cord Injury. AB - In a 43-yr-old male subject with a chronic T3 AIS A spinal cord injury, the acute cardiorespiratory responses to active upper-extremity exercise alone and combined active-arm passive-leg exercise (AAPLE) were investigated, along with the cardiorespiratory, cardiac, vascular, and body composition responses to a 6-wk AAPLE interval training intervention. AAPLE elicited superior acute maximal cardiorespiratory responses compared with upper-extremity exercise alone. In response to a 6-wk interval training regimen, AAPLE caused a 25% increase in peak oxygen uptake, a 10% increase in resting stroke volume, and a 4-fold increase in brachial artery blood flow. Conversely, there were no changes in femoral arterial function, body composition, or bone mineral density in response to training. As a potential clinical intervention, AAPLE may be advantageous over other forms of currently available exercise, owing to the minimal setup time and cost involved and the nonreliance on specialized equipment that is required for other exercise modalities. PMID- 26259053 TI - Effects of Transcutaneous Electrical Nerve Stimulation at Two Frequencies on Urinary Incontinence in Poststroke Patients: A Randomized Controlled Trial. AB - OBJECTIVE: The objective of this study was to compare the effects of two frequencies of transcutaneous electrical nerve stimulation (TENS) on urinary incontinence caused by stroke. METHODS: Eighty-one patients with poststroke urinary incontinence were recruited and randomized into the following three groups with a 1:1 ratio: a 20-Hz TENS group, a 75-Hz TENS group, and a no treatment control group (n = 27 per group). TENS currents were biphasic square waves with pulse durations of 150 MUsecs and pulse frequencies of 20 Hz or 75 Hz and were applied for 30 mins once per day for 90 days. The positive electrodes were placed in the region of the second sacral level on opposite sides of the vertebral column; the negative electrodes were placed on the inside of the middle and lower third of the junction between the posterior superior iliac spine and the ischial node. Overactive Bladder Symptom Scores, Barthel Index, urodynamic values, and voiding diary parameters were assessed before and after 90 days. RESULTS: The patients treated with 20 Hz had superior Overactive Bladder Symptom Scores, Barthel Index totals, urodynamic values, and voiding diary parameters (P < 0.05). In the 75-Hz group, values were statistically improved compared with the no-treatment group (P < 0.05), but the results were significantly inferior to those of the 20-Hz group (P < 0.05). CONCLUSIONS: Twenty-hertz TENS improved incontinence symptoms and promoted activities of daily living better than 75-Hz TENS. These results will aid future research regarding TENS parameters. PMID- 26259054 TI - Residency and Beyond: Subspecialization Trends Among Graduating Physiatry Residents and the Musculoskeletal Curriculum. AB - Previous studies and informal surveys have demonstrated a trend among graduating physiatry residents who desired to practice in an outpatient musculoskeletal (MSK)- or spine-type setting. However, there has been no updated information on the current trend among graduating residents as well as sparse information on gauging if current trainees feel prepared on graduation to treat patients with such disorders. This article describes a prospective survey of graduating chief residents during the 2013-2014 academic year in which 72% of chief residents planned to pursue a fellowship. A total of 54% of those chief residents planned to pursue a pain, sports, or spine fellowship. Seventy-five percent of the responding chief residents reported that most of the residents in their program felt that the current amount of required rotations in MSK, sports, spine, or pain medicine was adequate and 85% felt comfortable practicing in a noninterventional spine or MSK position after graduation without a fellowship. The results of this survey provide an updated perspective on the current trends among graduating residents as well as how residents perceive their MSK curriculum. These results may prove useful when evaluating MSK curriculums and shaping resident education to maximize career goals. PMID- 26259055 TI - Availability of Outpatient Rehabilitation Services for Children After Traumatic Brain Injury: Differences by Language and Insurance Status. AB - OBJECTIVE: The objective of this study was to explore associations between English proficiency, insurance status, outpatient rehabilitation service availability, and travel time for children with traumatic brain injury. DESIGN: The authors used an ecologic cross-sectional design. Data were analyzed from a cohort of 82 children with moderate to severe traumatic brain injury and rehabilitation providers in Washington State. Main measures included availability and travel time to services. RESULTS: Less than 20% of providers accepted children with Medicaid and provided language interpretation. Mental health services were most limited. Adjusted for median household income, multilingual service availability was lowest in counties with greater language diversity; for every 10% increase in persons older than 5 yrs speaking a language other than English at home, there was a 34% decrease in availability of multilingual services (prevalence ratio, 0.66; 95% confidence interval, 0.48-0.90). Adjusted for education and Medicaid status, children from Spanish-speaking families had significantly longer travel times to services (mean, 16 additional minutes to mental health; 9 to other therapies). CONCLUSIONS: Children in households with limited English proficiency and Medicaid faced significant barriers in availability and proximity of outpatient rehabilitation services. Innovative service strategies are needed to equitably improve availability of rehabilitation for children with traumatic brain injury. Similar studies in other regions will inform one's understanding of the scope of these disparities. PMID- 26259056 TI - From Wheelchair to Cane: Elective Transtibial Amputations in a Patient with Spina Bifida. AB - Spina bifida is associated with foot deformities, which may lead to foot ulcers, osteomyelitis, and limb amputation. Calcanectomy and Symes amputations have been reported successful in spina bifida. There is lack of evidence for transtibial amputations. This case describes a 27-yr-old woman with L4 level spina bifida who underwent bilateral transtibial amputations. She ambulated with bilateral ankle foot orthoses and canes until age 22. At age 22, she had bilateral foot reconstructive surgeries complicated by nonunion, ulcerations, and osteomyelitis. She was using a wheelchair by age 25. She had elective bilateral transtibial amputations at age 27 for progressive osteomyelitis. Four weeks after amputations, she was fit with bilateral prostheses. On completion of 2 mos of rehabilitation, she ambulated with a cane. This case demonstrates good functional outcomes after transtibial amputations in a young spina bifida patient. Prosthetic fitting should be considered for similar, previously high functioning spina bifida patients with transtibial amputation(s). PMID- 26259057 TI - Comment on: Evaluation of Stress and Pain in Young Children with Cerebral Palsy During Early Developmental Intervention Programs. PMID- 26259058 TI - Ultrasound-Guided Glenohumeral Joint Injection Using the Posterior Approach. PMID- 26259059 TI - Ultrasound-Guided Injection for the Treatment of Carpal Tunnel Syndrome. PMID- 26259060 TI - Syringomyelia: From the Cervicomedullary Junction to the Conus. PMID- 26259061 TI - Asymmetrical Lower Extremity Loading Early After Anterior Cruciate Ligament Reconstruction Is a Significant Predictor of Asymmetrical Loading at the Time of Return to Sport. AB - OBJECTIVES: The aim of this study was to examine whether asymmetrical lower limb loading early after anterior cruciate ligament reconstruction (1 mo) can predict asymmetrical lower limb loading at the time of return to sport (6 mos) and whether other early predictors as knee joint range of motion or maximal isometric strength affect this relationship. DESIGN: Ground reaction forces were measured during a sit-to-stand task 1 mo after anterior cruciate ligament reconstruction and a vertical countermovement jump 6 mos after anterior cruciate ligament reconstruction in 58 athletes. Other early postoperative measurements were knee joint range of motion (2 wks, 1 mo, and 2 mos after surgery) and maximal isometric strength of the knee extensor and flexor muscles (2 mos after surgery). Linear regression models were developed using side-to-side limb symmetry index (LSI) of countermovement jump as the dependent variable. RESULTS: LSI of sit-to stand task 1 mo after surgery was a significant independent predictor of LSI of countermovement jump 6 mos after surgery. After accounting for deficits in knee joint range of motion and LSI of maximal isometric strength (DeltaR2 = 0.35, P < 0.01), LSI of sit-to-stand task predicted LSI of countermovement jump (DeltaR2 = 0.14 P < 0.01). CONCLUSIONS: Asymmetrical lower extremity loading 1 mo after anterior cruciate ligament reconstruction is an early predictor of asymmetrical lower extremity loading 6 mos after surgery. PMID- 26259062 TI - Origins of female genital diversity: Predation risk and lock-and-key explain rapid divergence during an adaptive radiation. AB - The study of male genital diversity has long overshadowed evolutionary inquiry of female genitalia, despite its nontrivial diversity. Here, we identify four nonmutually exclusive mechanisms that could lead to genital divergence in females, and potentially generate patterns of correlated male-female genital evolution: (1) ecological variation alters the context of sexual selection ("ecology hypothesis"), (2) sexually antagonistic selection ("sexual-conflict hypothesis"), (3) female preferences for male genitalia mediated by female genital traits ("female-choice hypothesis"), and (4) selection against inter population mating ("lock-and-key hypothesis"). We performed an empirical investigation of all four hypotheses using the model system of Bahamas mosquitofish inhabiting blue holes that vary in predation risk. We found unequivocal support for the ecology hypothesis, with females exhibiting a smaller genital opening in blue holes containing piscivorous fish. This is consistent with stronger postmating female choice/conflict when predators are present, but greater premating female choice in their absence. Our results additionally supported the lock-and-key hypothesis, uncovering a pattern of reproductive character displacement for genital shape. We found no support for the sexual conflict or female choice hypotheses. Our results demonstrate a strong role for ecology in generating female genital diversity, and suggest that lock-and-key may provide a viable cause of female genital diversification. PMID- 26259063 TI - The Effectiveness of Integrated Care on Pediatric Behavioral Health: Outcomes and Opportunities. PMID- 26259064 TI - Satisfaction and Preference for Traditional Chinese Medicine Drugs Among Guardians of Children with Acute Bronchiolitis. AB - OBJECTIVES: To evaluate the satisfaction, concerns, and preference for Traditional Chinese Medicine (TCM) drugs among guardians of children with acute bronchiolitis, assess the agreement between satisfaction and preference, and explore the factors associated with satisfaction. DESIGN: A cross-sectional study was conducted in three main tertiary hospitals in Kunming, China, from September 2012 to July 2013 by structured questionnaire interviews. The characteristics of children and their guardians and guardians' satisfaction with and preference for TCM drugs were collected and analyzed by using chi-square or Fisher exact test. The agreement of satisfaction and preference was assessed by kappa and prevalence adjusted kappa coefficients. Multiple logistic regression was used to identify factors associated with satisfaction. RESULTS: A total of 286 guardians were enrolled in the study. Most children (97.6%) were younger than age 2 years. In total, the rates of satisfaction and preference for TCM drugs were 75.5% and 73.1%, respectively, and preference and satisfaction levels did not significantly differ between TCM and non-TCM hospitals. Guardians with higher socioeconomic status were more satisfied with TCM drugs, and the most common reason for preference for TCM drugs was that they had less toxicity or fewer adverse effects. Guardians were concerned most about safety and least concerned about cost. The agreement between satisfaction and preference was moderate in general (prevalence-adjusted kappa=0.42). CONCLUSIONS: Three fourths of the Chinese guardians of children with acute bronchiolitis were satisfied with and preferred the TCM drugs. Moderate agreement between satisfaction and preference was shown. PMID- 26259065 TI - Nexrutine inhibits azoxymethane-induced colonic aberrant crypt formation in rat colon and induced apoptotic cell death in colon adenocarcinoma cells. AB - Colon cancer is the third most common cause of death in the United States. Therefore, new preventive strategies are warranted for preventing colon cancer. Nexrutine (NX), an herbal extract from Phellodendron amurense, has been shown to have anti-inflammatory, anti-microbial and anti-cancer activity for various tissue specific cancers, but its chemopreventive efficacy has not been evaluated against colon cancer. Here, we explored the mechanism of chemopreventive/chemotherapeutic efficacy of NX against colon cancer. We found that dietary exposure of NX significantly reduced the number of azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rats. In addition, significant inhibition in AOM-induced cell proliferation and reduced expression of the inflammatory markers COX-2, iNOS as well as the proliferative markers PCNA and cyclin D1 were also seen. Moreover, NX exposure significantly enhanced apoptosis in the colon of AOM treated rats. Furthermore, in in vitro studies, NX (2.5, 5, 10 MUg/ml, 48 h) decreased cell survival and colony formation while inducing G0/G1 cell cycle arrest and apoptosis in colon adenocarcinoma cells COLO205 and HCT-15. However, NX had minimal cytotoxic effect on IEC-6 normal rat intestinal cells, suggesting its high therapeutic index. NX treatment also modulates the level of Bax and Bcl-2 proteins along with cytochrome c release, cleavage and enhanced expression of poly (adenosine diphosphate-ribose) polymerase as well as the catalytic activity of caspase 3 and caspase 9 in both COLO205 and HCT-15 cells. Based on these in vivo and in vitro findings, we suggest that NX could be useful candidate agent for colon cancer chemoprevention and treatment. (c) 2015 Wiley Periodicals, Inc. PMID- 26259068 TI - Rotational Mode Specificity in the F(-) + CH3Y [Y = F and Cl] SN2 Reactions. AB - More than 12 million quasiclassical trajectories are computed for the F(-) + CH3Y(v = 0, JK) [Y = F and Cl] SN2 reactions using full-dimensional ab initio analytical potential energy surfaces. The initial (J, K = 0) and (J, K = J) [J = 0, 2, 4, 6, 8] rotational state specific cross sections are obtained at different collision energies (Ecoll) in the 1-20 kcal mol(-1) range, and the scattering angle and initial attack angle distributions as well as the mechanism-specific opacity functions are reported at Ecoll = 10 kcal mol(-1). The tumbling rotation (K = 0) inhibits the F(-) + CH3F reaction by a factor of 3 for J = 8 at Ecoll = 10 kcal mol(-1). This tumbling rotational effect becomes smaller at low and high Ecoll, and the tumbling motion affects the cross sections of F(-) + CH3Cl by only a few percent. The spinning rotation (K = J) hinders both reactions by factors in the 1.3-1.7 range for J = 8 at low Ecoll, whereas slight promotion is found as the Ecoll increases. The tumbling rotation may counteract the attractive ion dipole forces, and the spinning motion hinders the complex formation, thereby decreasing the reactivity. PMID- 26259066 TI - Hydride bridge in [NiFe]-hydrogenase observed by nuclear resonance vibrational spectroscopy. AB - The metabolism of many anaerobes relies on [NiFe]-hydrogenases, whose characterization when bound to substrates has proven non-trivial. Presented here is direct evidence for a hydride bridge in the active site of the (57)Fe-labelled fully reduced Ni-R form of Desulfovibrio vulgaris Miyazaki F [NiFe]-hydrogenase. A unique 'wagging' mode involving H(-) motion perpendicular to the Ni(MU-H)(57)Fe plane was studied using (57)Fe-specific nuclear resonance vibrational spectroscopy and density functional theory (DFT) calculations. On Ni(MU-D)(57)Fe deuteride substitution, this wagging causes a characteristic perturbation of Fe CO/CN bands. Spectra have been interpreted by comparison with Ni(MU-H/D)(57)Fe enzyme mimics [(dppe)Ni(MU-pdt)(MU-H/D)(57)Fe(CO)3](+) and DFT calculations, which collectively indicate a low-spin Ni(II)(MU-H)Fe(II) core for Ni-R, with H( ) binding Ni more tightly than Fe. The present methodology is also relevant to characterizing Fe-H moieties in other important natural and synthetic catalysts. PMID- 26259067 TI - Good Publication Practice for Communicating Company-Sponsored Medical Research: GPP3. AB - This updated Good Publication Practice (GPP) guideline, known as GPP3, builds on earlier versions and provides recommendations for individuals and organizations that contribute to the publication of research results sponsored or supported by pharmaceutical, medical device, diagnostics, and biotechnology companies. The recommendations are designed to help individuals and organizations maintain ethical and transparent publication practices and comply with legal and regulatory requirements. These recommendations cover publications in peer reviewed journals and presentations (oral or poster) at scientific congresses. The International Society for Medical Publication Professionals invited more than 3000 professionals worldwide to apply for a position on the steering committee, or as a reviewer, for this guideline. The GPP2 authors reviewed all applications (n = 241) and assembled an 18-member steering committee that represented 7 countries and a diversity of publication professions and institutions. From the 174 selected reviewers, 94 sent comments on the second draft, which steering committee members incorporated after discussion and consensus. The resulting guideline includes new sections (Principles of Good Publication Practice for Company-Sponsored Medical Research, Data Sharing, Studies That Should Be Published, and Plagiarism), expands guidance on the International Committee of Medical Journal Editors' authorship criteria and common authorship issues, improves clarity on appropriate author payment and reimbursement, and expands information on the role of medical writers. By following good publication practices (including GPP3), individuals and organizations will show integrity; accountability; and responsibility for accurate, complete, and transparent reporting in their publications and presentations. PMID- 26259069 TI - IgG4-related disease. AB - Immunoglobulin G4-related disease (IgG4-RD) is a regional or systemic fibro inflammatory disease of unknown etiology. It presents a distinctive histopathological appearance of dense lymphoplasmacytic infiltrates with abundant IgG4-positive plasma cells, storiform fibrosis and obliterative phlebitis with the appearance of inflammatory swelling or tumefactive lesions. This new disease entity includes a wide variety of diseases such as Mikulicz disease, autoimmune pancreatitis, Riedel thyroiditis, interstitial nephritis and retroperitoneal fibrosis. Glucocorticoid therapy can resolve the clinical and pathological abnormalities and impaired organ function. IgG4-RD was recognized internationally in 2011, and new evidence has accumulated regarding its pathogenesis, clinical features and treatment. In this review, we outline our present understanding of IgG4-RD. PMID- 26259070 TI - Oral bacteria in placental tissues: increased molecular detection in pregnant periodontitis patients. AB - OBJECTIVES: The objective of this study was to identify the DNA of oral bacteria in placental samples from women with and without periodontitis who had or had not had preterm births and/or low birthweight (PB/LBW) neonates. METHODS: Data were gathered from 57 puerperal women in relation to socio-demographic, gynaecological, and periodontal variables and to placental histomorphology. Fifty seven biopsies, 28 from mothers with periodontitis, were taken aseptically from preterm placentas (n = 36) and from full-term placentas (n = 21). Total DNA was extracted, and the presence of 15 oral bacteria was assessed using Nested-PCR. RESULTS: The placentas from women with periodontitis showed a higher prevalence of periodontopathogens compared to those from women without periodontitis (P = 0.009). Samples showed low prevalences of Actinomyces israelii, Parvimonas micra and Tannerella forsythia. An association was found between Eikenella corrodens in placenta and periodontitis (P = 0.002). The most ubiquitous bacterium, Fusobacterium nucleatum, was more prevalent in mothers with periodontitis and PB/LBW (P = 0.033). Porphyromonas gingivalis, Treponema denticola, Prevotella intermedia and Aggregatibacter actinomycetemcomitans were not detected. CONCLUSIONS: These results, along with previous findings, show that oral bacteria may be normally present in the placenta, however, the levels of certain oral pathogens in the placenta would highly depend on the mother's periodontal state. PMID- 26259072 TI - Microscopic Pattern of Bone Fractures as an Indicator of Blast Trauma: A Pilot Study. AB - The assessment of fractures is a key issue in forensic anthropology; however, very few studies deal with the features of fractures due to explosion in comparison with other traumatic injuries. This study focuses on fractures resulting from blast trauma and two types of blunt force trauma (manual compression and running over), applied to corpses of pigs; 163 osteons were examined within forty fractures by the transmission light microscopy. Blast lesions showed a higher percentage of fracture lines through the Haversian canal, whereas in other types of trauma, the fractures went across the inner lamellae. Significant differences between samples hit by blast energy and those runover or manually compressed were observed (p<0.05). The frequency of pattern A is significantly higher in exploded bones than in runover and compressed. Microscopic analysis of the fracture line may provide information about the type of trauma, especially for what concerns blast trauma. PMID- 26259071 TI - Genome-wide analysis of the genetic regulation of gene expression in human neutrophils. AB - Neutrophils are an abundant immune cell type involved in both antimicrobial defence and autoimmunity. The regulation of their gene expression, however, is still largely unknown. Here we report an eQTL study on isolated neutrophils from 114 healthy individuals of Chinese ethnicity, identifying 21,210 eQTLs on 832 unique genes. Unsupervised clustering analysis of these eQTLs confirms their role in inflammatory responses and immunological diseases but also indicates strong involvement in dermatological pathologies. One of the strongest eQTL identified (rs2058660) is also the tagSNP of a linkage block reported to affect leprosy and Crohn's disease in opposite directions. In a functional study, we can link the C allele with low expression of the beta-chain of IL18-receptor (IL18RAP). In neutrophils, this results in a reduced responsiveness to IL-18, detected both on the RNA and protein level. Thus, the polymorphic regulation of human neutrophils can impact beneficial as well as pathological inflammatory responses. PMID- 26259073 TI - Metric Sex Determination of the Human Coxal Bone on a Virtual Sample using Decision Trees. AB - Decision trees provide an alternative to multivariate discriminant analysis, which is still the most commonly used in anthropometric studies. Our study analyzed the metric characterization of a recent virtual sample of 113 coxal bones using decision trees for sex determination. From 17 osteometric type I landmarks, a dataset was built with five classic distances traditionally reported in the literature and six new distances selected using the two-step ratio method. A ten-fold cross-validation was performed, and a decision tree was established on two subsamples (training and test sets). The decision tree established on the training set included three nodes and its application to the test set correctly classified 92% of individuals. This percentage was similar to the data of the literature. The usefulness of decision trees has been demonstrated in numerous fields. They have been already used in sex determination, body mass prediction, and ancestry estimation. This study shows another use of decision trees enabling simple and accurate sex determination. PMID- 26259074 TI - A Telemedicine-Based Intervention Reduces the Frequency and Severity of COPD Exacerbation Symptoms: A Randomized, Controlled Trial. AB - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) may not recognize worsening symptoms that require intensification of therapy. They may also be reluctant to contact a healthcare provider for minor worsening of symptoms. A telemedicine application for daily symptom reporting may reduce these barriers and improve patient outcomes. MATERIALS AND METHODS: Patients hospitalized for a COPD exacerbation within the past year or using supplemental O2 were approached for participation. Patients received optimal COPD care and were given a telecommunication device for symptom reporting. Initial symptom scores were obtained while patients were in their usual state of health. Patients were randomly assigned to an intervention group or a control group (usual medical care). The control group patients were instructed to seek medical care if their condition worsened. The intervention group symptom scores were assessed by a computer algorithm and compared with initial values. Scores 1 or more points above the initial score generated an "alert," and patients were reviewed by a nurse and referred to a physician who prescribed treatment. RESULTS: Eighty-six patients were screened; 79 met entry criteria and were randomized (intervention group, n=39; control group, n=40). Twelve patients submitted five or fewer symptom reports (5 intervention; 7 control) and were excluded from the analysis. Daily peak flow and dyspnea scores improved only in the intervention group. There were no differences in hospitalization and mortality rates between groups. No serious adverse events were reported. CONCLUSIONS: A telemedicine-based symptom reporting program facilitated early treatment of symptoms and improved lung function and functional status. PMID- 26259075 TI - The 8 basic payment methods in health care. AB - Eight basic payment methods are applicable across all types of health care. Each method is defined by the unit of payment (per time period, beneficiary, recipient, episode, day, service, dollar of cost, or dollar of charges). These methods are more specific than common terms, such as capitation, fee for service, global payment, and cost reimbursement. They also correspond to the division of financial risk between payer and provider, with each method reflecting a risk factor within the health care spending identity. Financial risk gradually shifts from being primarily on providers when payment is per time period to being primarily on payers when payment is per dollar of charges. Method 4 (per episode) marks the line between epidemiologic and treatment risk. The 8 methods are typically combined to balance risk and thus balance incentives between payers and providers. This taxonomy makes it easier to understand trends in payment reform especially the shifting division of financial risk and the movement toward value based purchasing-and types of payment reform, such as bundling, accountable care organizations, medical homes, and cost sharing. The taxonomy also enables prediction of conflicts between payers and providers. For each unit of payment, providers are rewarded for increasing units while decreasing their own cost per unit. No payment method is neutral on quality because each encourages and discourages the provision of care overall and in particular situations. Many professional norms and business practices have been established to mitigate undesirable incentives. Health care differs from many other industries in that the unit of payment remains variable and unsettled. PMID- 26259077 TI - Learning Super-Resolution Jointly From External and Internal Examples. AB - Single image super-resolution (SR) aims to estimate a high-resolution (HR) image from a low-resolution (LR) input. Image priors are commonly learned to regularize the, otherwise, seriously ill-posed SR problem, either using external LR-HR pairs or internal similar patterns. We propose joint SR to adaptively combine the advantages of both external and internal SR methods. We define two loss functions using sparse coding-based external examples, and epitomic matching based on internal examples, as well as a corresponding adaptive weight to automatically balance their contributions according to their reconstruction errors. Extensive SR results demonstrate the effectiveness of the proposed method over the existing state-of-the-art methods, and is also verified by our subjective evaluation study. PMID- 26259076 TI - Treosulfan-based conditioning regimens for allogeneic haematopoietic stem cell transplantation in children with non-malignant diseases. AB - An increasing number of children with non-malignant diseases can be cured by allogeneic haematopoietic stem cell transplantation (HSCT). Treosulfan (L-treitol 1,4-bis-methanesulfonate) is being used more frequently for conditioning, owing to its' lower toxicity profile compared with conventional myeloablative regimens. A retrospective analysis was performed of children registered in the EBMT database, who received treosulfan before HSCT between January 2005 and 2010, to identify possible dose-related toxicity and determine the incidence of engraftment, treatment-related mortality and overall survival (OS). Results from 316 transplants from 11 different countries are presented. Ninety-five (30%) were under 1 year of age at the time of transplant. OS was 83% and event-free survival was 76%; 3-year OS and event-free survival of infants below 1 year were 79% and 73%, respectively. No association was found with age at transplant, dose of treosulfan given, other agents used in combination with treosulfan, donor type, stem cell source, or second or subsequent transplant. In this report of the largest number of children to date receiving treosulfan for non-malignant diseases, treosulfan is shown to be a safe and effective agent even for those under 1 year of age at the time of transplant. Further prospective studies are needed using precisely defined protocols with pharmacokinetic monitoring and detailed chimerism analysis. In addition, long-term studies will be vital to determine long-term effects, for example, on fertility in comparison with other regimens. PMID- 26259078 TI - Perceptual Quality Assessment of Screen Content Images. AB - Research on screen content images (SCIs) becomes important as they are increasingly used in multi-device communication applications. In this paper, we present a study on perceptual quality assessment of distorted SCIs subjectively and objectively. We construct a large-scale screen image quality assessment database (SIQAD) consisting of 20 source and 980 distorted SCIs. In order to get the subjective quality scores and investigate, which part (text or picture) contributes more to the overall visual quality, the single stimulus methodology with 11 point numerical scale is employed to obtain three kinds of subjective scores corresponding to the entire, textual, and pictorial regions, respectively. According to the analysis of subjective data, we propose a weighting strategy to account for the correlation among these three kinds of subjective scores. Furthermore, we design an objective metric to measure the visual quality of distorted SCIs by considering the visual difference of textual and pictorial regions. The experimental results demonstrate that the proposed SCI perceptual quality assessment scheme, consisting of the objective metric and the weighting strategy, can achieve better performance than 11 state-of-the-art IQA methods. To the best of our knowledge, the SIQAD is the first large-scale database published for quality evaluation of SCIs, and this research is the first attempt to explore the perceptual quality assessment of distorted SCIs. PMID- 26259079 TI - Recognizing Actions Through Action-Specific Person Detection. AB - Action recognition in still images is a challenging problem in computer vision. To facilitate comparative evaluation independently of person detection, the standard evaluation protocol for action recognition uses an oracle person detector to obtain perfect bounding box information at both training and test time. The assumption is that, in practice, a general person detector will provide candidate bounding boxes for action recognition. In this paper, we argue that this paradigm is suboptimal and that action class labels should already be considered during the detection stage. Motivated by the observation that body pose is strongly conditioned on action class, we show that: 1) the existing state of-the-art generic person detectors are not adequate for proposing candidate bounding boxes for action classification; 2) due to limited training examples, the direct training of action-specific person detectors is also inadequate; and 3) using only a small number of labeled action examples, the transfer learning is able to adapt an existing detector to propose higher quality bounding boxes for subsequent action classification. To the best of our knowledge, we are the first to investigate transfer learning for the task of action-specific person detection in still images. We perform extensive experiments on two benchmark data sets: 1) Stanford-40 and 2) PASCAL VOC 2012. For the action detection task (i.e., both person localization and classification of the action performed), our approach outperforms methods based on general person detection by 5.7% mean average precision (MAP) on Stanford-40 and 2.1% MAP on PASCAL VOC 2012. Our approach also significantly outperforms the state of the art with a MAP of 45.4% on Stanford-40 and 31.4% on PASCAL VOC 2012. We also evaluate our action detection approach for the task of action classification (i.e., recognizing actions without localizing them). For this task, our approach, without using any ground-truth person localization at test time, outperforms on both data sets state-of-the-art methods, which do use person locations. PMID- 26259080 TI - Robust and Non-Negative Collective Matrix Factorization for Text-to-Image Transfer Learning. AB - Heterogeneous transfer learning has recently gained much attention as a new machine learning paradigm in which the knowledge can be transferred from source domains to target domains in different feature spaces. Existing works usually assume that source domains can provide accurate and useful knowledge to be transferred to target domains for learning. In practice, there may be noise appearing in given source (text) and target (image) domains data, and thus, the performance of transfer learning can be seriously degraded. In this paper, we propose a robust and non-negative collective matrix factorization model to handle noise in text-to-image transfer learning, and make a reliable bridge to transfer accurate and useful knowledge from the text domain to the image domain. The proposed matrix factorization model can be solved by an efficient iterative method, and the convergence of the iterative method can be shown. Extensive experiments on real data sets suggest that the proposed model is able to effectively perform transfer learning in noisy text and image domains, and it is superior to the popular existing methods for text-to-image transfer learning. PMID- 26259081 TI - Shadow Remover: Image Shadow Removal Based on Illumination Recovering Optimization. AB - In this paper, we present a novel shadow removal system for single natural images as well as color aerial images using an illumination recovering optimization method. We first adaptively decompose the input image into overlapped patches according to the shadow distribution. Then, by building the correspondence between the shadow patch and the lit patch based on texture similarity, we construct an optimized illumination recovering operator, which effectively removes the shadows and recovers the texture detail under the shadow patches. Based on coherent optimization processing among the neighboring patches, we finally produce high-quality shadow-free results with consistent illumination. Our shadow removal system is simple and effective, and can process shadow images with rich texture types and nonuniform shadows. The illumination of shadow-free results is consistent with that of surrounding environment. We further present several shadow editing applications to illustrate the versatility of the proposed method. PMID- 26259082 TI - Multispectral Image Out-of-Focus Deblurring Using Interchannel Correlation. AB - Out-of-focus blur occurs frequently in multispectral imaging systems when the camera is well focused at a specific (reference) imaging channel. As the effective focal lengths of the lens are wavelength dependent, the blurriness levels of the images at individual channels are different. This paper proposes a multispectral image deblurring framework to restore out-of-focus spectral images based on the characteristic of interchannel correlation (ICC). The ICC is investigated based on the fact that a high-dimensional color spectrum can be linearly approximated using rather a few number of intrinsic spectra. In the method, the spectral images are classified into an out-of-focus set and a well focused set via blurriness computation. For each out-of-focus image, a guiding image is derived from the well-focused spectral images and is used as the image prior in the deblurring framework. The out-of-focus blur is modeled as a Gaussian point spread function, which is further employed as the blur kernel prior. The regularization parameters in the image deblurring framework are determined using generalized cross validation, and thus the proposed method does not need any parameter tuning. The experimental results validate that the method performs well on multispectral image deblurring and outperforms the state of the arts. PMID- 26259083 TI - Multi-Spectral Fusion Based Approach for Arbitrarily Oriented Scene Text Detection in Video Images. AB - Scene text detection from video as well as natural scene images is challenging due to the variations in background, contrast, text type, font type, font size, and so on. Besides, arbitrary orientations of texts with multi-scripts add more complexity to the problem. The proposed approach introduces a new idea of convolving Laplacian with wavelet sub-bands at different levels in the frequency domain for enhancing low resolution text pixels. Then, the results obtained from different sub-bands (spectral) are fused for detecting candidate text pixels. We explore maxima stable extreme regions along with stroke width transform for detecting candidate text regions. Text alignment is done based on the distance between the nearest neighbor clusters of candidate text regions. In addition, the approach presents a new symmetry driven nearest neighbor for restoring full text lines. We conduct experiments on our collected video data as well as several benchmark data sets, such as ICDAR 2011, ICDAR 2013, and MSRA-TD500 to evaluate the proposed method. The proposed approach is compared with the state-of-the-art methods to show its superiority to the existing methods. PMID- 26259084 TI - From Local Similarities to Global Coding: A Framework for Coding Applications. AB - Feature coding has received great attention in recent years as a building block of many image processing algorithms. In particular, the importance of the locality assumption in coding approaches has been studied in many previous works. We review this assumption and claim that using the similarity of data points to a more global set of anchor points does not necessarily weaken the coding method, as long as the underlying structure of the anchor points is considered. We propose to capture the underlying structure by assuming a random walker over the anchor points. We also show that our method is a fast approximation to the diffusion map kernel. Experiments on various data sets show that with a knowledge of the underlying structure of anchor points, different state-of-the-art coding algorithms may boost their performance in different learning tasks by utilizing the proposed method. PMID- 26259085 TI - Translating Alcohol Research: Opportunities and Challenges. AB - Alcohol use disorder (AUD) and its sequelae impose a major burden on the public health of the United States, and adequate long-term control of this disorder has not been achieved. Molecular and behavioral basic science research findings are providing the groundwork for understanding the mechanisms underlying AUD and have identified multiple candidate targets for ongoing clinical trials. However, the translation of basic research or clinical findings into improved therapeutic approaches for AUD must become more efficient. Translational research is a multistage process of stream-lining the movement of basic biomedical research findings into clinical research and then to the clinical target populations. This process demands efficient bidirectional communication across basic, applied, and clinical science as well as with clinical practitioners. Ongoing work suggests rapid progress is being made with an evolving translational framework within the alcohol research field. This is helped by multiple interdisciplinary collaborative research structures that have been developed to advance translational work on AUD. Moreover, the integration of systems biology approaches with collaborative clinical studies may yield novel insights for future translational success. Finally, appreciation of genetic variation in pharmacological or behavioral treatment responses and optimal communication from bench to bedside and back may strengthen the success of translational research applications to AUD. PMID- 26259087 TI - Cognitive Neuroscience Approaches to Understanding Behavior Change in Alcohol Use Disorder Treatments. AB - Researchers have begun to apply cognitive neuroscience concepts and methods to study behavior change mechanisms in alcohol use disorder (AUD) treatments. This review begins with an examination of the current state of treatment mechanisms research using clinical and social psychological approaches. It then summarizes what is currently understood about the pathophysiology of addiction from a cognitive neuroscience perspective. Finally, it reviews recent efforts to use cognitive neuroscience approaches to understand the neural mechanisms of behavior change in AUD, including studies that use neural functioning to predict relapse and abstinence; studies examining neural mechanisms that operate in current evidence-based behavioral interventions for AUD; as well as research on novel behavioral interventions that are being derived from our emerging understanding of the neural and cognitive mechanisms of behavior change in AUD. The article highlights how the regulation of subcortical regions involved in alcohol incentive motivation by prefrontal cortical regions involved in cognitive control may be a core mechanism that plays a role in these varied forms of behavior change in AUD. We also lay out a multilevel framework for integrating cognitive neuroscience approaches with more traditional methods for examining AUD treatment mechanisms. PMID- 26259086 TI - Advances in Medications and Tailoring Treatment for Alcohol Use Disorder. AB - Alcohol use disorder (AUD) is a chronic heritable brain disorder with a variable clinical presentation. This variability, or heterogeneity, in clinical presentation suggests complex interactions between environmental and biological factors, resulting in several underlying pathophysiological mechanisms in the development and progression of AUD. Classifying AUD into subgroups of common clinical or pathological characteristics would ease the complexity of teasing apart underlying molecular mechanisms. Genetic association analyses have revealed several polymorphisms-small differences in DNA-that increase a person's vulnerability to develop AUD and other alcohol-related intermediate characteristics, such as severity of drinking, age of AUD onset, or measures of craving. They also have identified polymorphisms associated with reduced drinking. Researchers have begun utilizing these genetic polymorphisms to identify alcoholics who might respond best to various treatments, thereby enhancing the effectiveness of currently tested medications for treating AUD. This review compares the efficacy of medications tested for treatment of AUD with and without incorporating genetics. It then discusses advances in pre-clinical genetic and genomic studies that potentially could be adapted to clinical trials to improve treatment efficacy. Although a pharmacogenetic approach is promising, it is relatively new and will need to overcome many challenges, including inadequate scientific knowledge and social and logistic constraints, to be utilized in clinical practice. PMID- 26259088 TI - Utilization of Magnetic Resonance Imaging in Research Involving Animal Models of Fetal Alcohol Spectrum Disorders. AB - It is well recognized that fetal alcohol exposure can profoundly damage the developing brain. The term fetal alcohol spectrum disorder (FASD) describes the range of deficits that result from prenatal alcohol exposure. Over the past two decades, researchers have used magnetic resonance imaging (MRI) as a noninvasive technique to characterize anatomical, physiological, and metabolic changes in the human brain that are part of FASD. As using animal models can circumvent many of the complications inherent to human studies, researchers have established and explored a number of models involving a range of species. Using MRI-based modalities, the FASD animal models have demonstrated decreased brain volume and abnormal brain shape, disrupted cellular morphology differentiation, altered neurochemistry, and blood perfusion. These animal studies have facilitated characterization of the direct effects of ethanol; in many cases identifying specific sequelae related to the timing and dose of exposure. Further, as a result of the ability to perform traditional (such as histological) analyses on animal brains following neuroimaging experiments, this work leads to improvements in the accuracy of our interpretations of neuroimaging findings in human studies. PMID- 26259090 TI - Advances in Human Neuroconnectivity Research: Applications for Understanding Familial History Risk for Alcoholism. AB - Recent advances in brain imaging have allowed researchers to further study the networks connecting brain regions. Specifically, research examining the functioning of these networks in groups with a genetic predisposition for alcoholism has found atypical circuitry in the brains of such individuals. Further research with larger sample sizes and multimodal method integration are necessary to confirm these intriguing findings. PMID- 26259091 TI - Advances in Diagnosis and Treatment of Fetal Alcohol Spectrum Disorders: From Animal Models to Human Studies. AB - Prenatal alcohol exposure can cause a number of physical, behavioral, cognitive, and neural impairments, collectively known as fetal alcohol spectrum disorders (FASD). This article examines basic research that has been or could be translated into practical applications for the diagnosis or treatment of FASD. Diagnosing FASD continues to be a challenge, but advances are being made at both basic science and clinical levels. These include identification of biomarkers, recognition of subtle facial characteristics of exposure, and examination of the relation between face, brain, and behavior. Basic research also is pointing toward potential new interventions for FASD involving pharmacotherapies, nutritional therapies, and exercise interventions. Although researchers have assessed the majority of these treatments in animal models of FASD, a limited number of recent clinical studies exist. An assessment of this literature suggests that targeted interventions can improve some impairments resulting from developmental alcohol exposure. However, combining interventions may prove more efficacious. Ultimately, advances in basic and clinical sciences may translate to clinical care, improving both diagnosis and treatment. PMID- 26259092 TI - Mechanisms of Neuroplasticity and Ethanol's Effects on Plasticity in the Striatum and Bed Nucleus of the Stria Terminalis. AB - Long-lasting changes in synaptic function (i.e., synaptic plasticity) have long been thought to contribute to information storage in the nervous system. Although synaptic plasticity mainly has adaptive functions that allow the organism to function in complex environments, it is now clear that certain events or exposure to various substances can produce plasticity that has negative consequences for organisms. Exposure to drugs of abuse, in particular ethanol, is a life experience that can activate or alter synaptic plasticity, often resulting in increased drug seeking and taking and in many cases addiction.Two brain regions subject to alcohol's effects on synaptic plasticity are the striatum and bed nucleus of the stria terminalis (BNST), both of which have key roles in alcohol's actions and control of intake. The specific effects depend on both the brain region analyzed (e.g., specific subregions of the striatum and BNST) and the duration of ethanol exposure (i.e., acute vs. chronic). Plastic changes in synaptic transmission in these two brain regions following prolonged ethanol exposure are thought to contribute to excessive alcohol drinking and relapse to drinking. Understanding the mechanisms underlying this plasticity may lead to new therapies for treatment of these and other aspects of alcohol use disorder. PMID- 26259093 TI - Neuroplasticity in Human Alcoholism: Studies of Extended Abstinence with Potential Treatment Implications. AB - Alcoholism is characterized by a lack of control over excessive alcohol consumption despite significant negative consequences. This impulsive and compulsive behavior may be related to functional abnormalities within networks of brain regions responsible for how we make decisions. The abnormalities may result in strengthened networks related to appetitive drive-or the need to fulfill desires-and simultaneously weakened networks that exercise control over behaviors. Studies using functional magnetic resonance imaging (fMRI) in abstinent alcoholics suggest that abstinence is associated with changes in the tone of such networks, decreasing resting tone in appetitive drive networks, and increasing resting tone in inhibitory control networks to support continued abstinence. Identifying electroencephalographic (EEG) measures of resting tone in these networks initially identified using fMRI, and establishing in longitudinal studies that these abstinence-related changes in network tone are progressive would motivate treatment initiatives to facilitate these changes in network tone, thereby supporting successful ongoing abstinence. PMID- 26259095 TI - Impact of salinity and dispersed oil on adsorption of dissolved aromatic hydrocarbons by activated carbon and organoclay. AB - Adsorption capacity of phenol and naphthalene by powdered activated carbon (PAC), a commercial organoclay (OC) and a lab synthesized organoclay (BTMA) was studied using batch adsorption experiments under variable feed water quality conditions including single- and multi- solute conditions, fresh water, saline water and oily-and-saline water. Increasing salinity levels was found to reduce adsorption capacity of OC, likely due to destabilization, aggregation and subsequent removal of organoclay from the water column, but did not negatively impact adsorption capacity of PAC or BTMA. Increased dispersed oil concentrations were found to reduce the surface area of all adsorbents. This decreased the adsorption capacity of PAC for both phenol and naphthalene, and reduced BTMA adsorption of phenol, but did not negatively affect naphthalene removals by either organoclay. The presence of naphthalene as a co-solute significantly reduced phenol adsorption by PAC, but had no impact on organoclay adsorption. These results indicated that adsorption by PAC occurred via a surface adsorption mechanism, while organoclay adsorption occurred by hydrophobic or pi electron interactions. In general, PAC was more sensitive to changes in water quality than either of the organoclays evaluated in this study. However, PAC exhibited a higher adsorption capacity for phenol and naphthalene compared to both organoclays even in adverse water quality conditions. PMID- 26259094 TI - Neuroplasticity and Predictors of Alcohol Recovery. AB - Chronic alcohol-related neuroadaptations in key neural circuits of emotional and cognitive control play a critical role in the development of, and recovery from, alcoholism. Converging evidence in the neurobiological literature indicates that neuroplastic changes in the prefrontal-striatal-limbic circuit, which governs emotion regulation and decisionmaking and controls physiological responses in the autonomic nervous system and hypothalamic-pituitary-adrenal axis system, contribute to chronic alcoholism and also are significant predictors of relapse and recovery. This paper reviews recent evidence on the neuroplasticity associated with alcoholism in humans, including acute and chronic effects, and how these neurobiological adaptations contribute to alcohol recovery, along with the discussion of relevant clinical implications and future research directions. PMID- 26259096 TI - Super-high photocatalytic activity, stability and improved photocatalytic mechanism of monodisperse AgBr doped with In. AB - Monodisperse In(3+) doped AgBr (In-AgBr) nanoparticles were synthesized by a hydrothermal route. The pure AgBr and In-AgBr samples were investigated by X-ray powder diffraction, transmission electron microscopy, ultraviolet-visible absorption spectroscopy, X-ray photoelectron spectroscopy, measurement of total organic carbon, and electron paramagnetic resonance spectrometry. In-AgBr was more photocatalytically active than pure AgBr in photodegradation of 20 mg/L methyl orange under visible light irradiation (lambda>420 nm). The 0.05 mol/L In AgBr sample showed the highest photodegradation efficiency and high stability. The doped In(3+) expanded the light absorption range, reduced the band gap of AgBr and improved the utilization of photons. The additional In(3+) can inhibit the formation of Ag particles on the surface of AgBr, which can further stabilize AgBr. The doped In(3+) in AgBr served as a temporary site for trapping of photoinduced electrons, and thereby obviously restrained the recombination of photoinduced electron-hole pairs on the surface of AgBr. The enhanced photocatalytic ability of In-AgBr may be mainly attributed to the improved separation efficiency of photogenerated charges. PMID- 26259089 TI - Advances in Electrophysiological Research. AB - Electrophysiological measures of brain function are effective tools to understand neurocognitive phenomena and sensitive indicators of pathophysiological processes associated with various clinical conditions, including alcoholism. Individuals with alcohol use disorder (AUD) and their high-risk offspring have consistently shown dysfunction in several electrophysiological measures in resting state (i.e., electroencephalogram) and during cognitive tasks (i.e., event-related potentials and event-related oscillations). Researchers have recently developed sophisticated signal-processing techniques to characterize different aspects of brain dynamics, which can aid in identifying the neural mechanisms underlying alcoholism and other related complex disorders.These quantitative measures of brain function also have been successfully used as endophenotypes to identify and help understand genes associated with AUD and related disorders. Translational research also is examining how brain electrophysiological measures potentially can be applied to diagnosis, prevention, and treatment. PMID- 26259097 TI - Fluctuation of dissolved heavy metal concentrations in the leachate from anaerobic digestion of municipal solid waste in commercial scale landfill bioreactors: The effect of pH and associated mechanisms. AB - Heavy metals present in landfill leachate have infrequently been related to complete anaerobic degradation municipal solid waste (MSW) due to discrete ages of deposited MSW layers and leachate channelling in landfills. In this study, anaerobic digestion of MSW was performed in two enclosed 1000 tonne bioreactors using a unique flood and drain process. Leachates were characterised in terms of pH, soluble chemical oxygen demand, volatile fatty acids (VFAs), ammonium nitrogen and heavy metals over the entire course of digestion. All parameters, including pH, fluctuated during acidogenesis, acetogenesis and methanogenesis, which strongly impacted on the dynamics of dissolved heavy metal concentrations. The simulation of dissolution and precipitation processes indicated that metal sulphide precipitation was not a factor as metal concentrations exceeded solubility limits. The correlation of pH and dissolved heavy metal concentrations indicated that other, mechanisms were involved in the homogenised conditions within the bioreactors. Beside dissolution and precipitation, the main processes most likely involved in metal distributions were adsorption (Zn, Cu, Ni, Pb and Cd), complexation (Cr) or combinations of both process (As and Co). PMID- 26259098 TI - Music evokes vivid autobiographical memories. AB - Music is strongly intertwined with memories-for example, hearing a song from the past can transport you back in time, triggering the sights, sounds, and feelings of a specific event. This association between music and vivid autobiographical memory is intuitively apparent, but the idea that music is intimately tied with memories, seemingly more so than other potent memory cues (e.g., familiar faces), has not been empirically tested. Here, we compared memories evoked by music to those evoked by famous faces, predicting that music-evoked autobiographical memories (MEAMs) would be more vivid. Participants listened to 30 songs, viewed 30 faces, and reported on memories that were evoked. Memories were transcribed and coded for vividness as in Levine, B., Svoboda, E., Hay, J. F., Winocur, G., & Moscovitch, M. [2002. Aging and autobiographical memory: Dissociating episodic from semantic retrieval. Psychology and Aging, 17, 677-689]. In support of our hypothesis, MEAMs were more vivid than autobiographical memories evoked by faces. MEAMs contained a greater proportion of internal details and a greater number of perceptual details, while face-evoked memories contained a greater number of external details. Additionally, we identified sex differences in memory vividness: for both stimulus categories, women retrieved more vivid memories than men. The results show that music not only effectively evokes autobiographical memories, but that these memories are more vivid than those evoked by famous faces. PMID- 26259099 TI - Nationwide survey of Streptococcus pneumoniae drug resistance in the pediatric field in Japan. AB - BACKGROUND: Streptococcus pneumoniae is a major causative pathogen of pneumonia in children. The Drug-Resistant Pathogen Surveillance Group in Pediatric Infectious Disease conducted a nationwide surveillance of S. pneumoniae in 2000 2001, 2004, 2007, 2010 and 2012, and investigated changes in drug resistance of S. pneumoniae. METHODS: All strains of S. pneumoniae were isolated from clinical specimens collected from pediatric patients. The minimun inhibitory concentration was measured and the strains were classified according to the Clinical Laboratory Standards Institute criteria. The isolation rates of penicillin-intermediate resistant S. pneumoniae (PISP) and penicillin-resistant S. pneumoniae (PRSP) were compared based on seven patient factors. Logistic regression analysis was also performed. RESULTS: The sum of the isolation rates for PISP and PRSP for each period was 64.6%, 67.0%, 56.2%, 76.9% and 49.5%, respectively. Among the patient factors, age category 1 (<3 years, >=3 years), age category 2 (infant, toddler and preschooler, schoolchild), siblings (absence, presence), and pre-treatment with antimicrobial agents (absence, presence) were associated with significant differences in the isolation rate of PISP + PRSP. An interaction was observed between pre-treatment with antimicrobial agents and schoolchild, and the isolation rate of PISP + PRSP was higher in patients with both pre-treatment with antimicrobial agents and schoolchild. CONCLUSION: Although some changes were observed in the rate of resistance of S. pneumoniae, an increasing trend was not observed. Both pre-treatment with antimicrobial agents and age were associated with resistance, and an interaction was observed between pre-treatment with antimicrobial agents and schoolchild. PMID- 26259100 TI - Tuning of Magnetic Optical Response in a Dielectric Nanoparticle by Ultrafast Photoexcitation of Dense Electron-Hole Plasma. AB - We propose a novel approach for efficient tuning of optical properties of a high refractive index subwavelength nanoparticle with a magnetic Mie-type resonance by means of femtosecond laser irradiation. This concept is based on ultrafast photoinjection of dense (>10(20) cm(-3)) electron-hole plasma within such nanoparticle, drastically changing its transient dielectric permittivity. This allows manipulation by both electric and magnetic nanoparticle responses, resulting in dramatic changes of its scattering diagram and scattering cross section. We experimentally demonstrate 20% tuning of reflectance of a single silicon nanoparticle by femtosecond laser pulses with wavelength in the vicinity of the magnetic dipole resonance. Such a single-particle nanodevice enables designing of fast and ultracompact optical switchers and modulators. PMID- 26259102 TI - Stability of Grafted Polymer Nanoscale Films toward Gamma Irradiation. AB - The present article focuses on the influence of gamma irradiation on nanoscale polymer grafted films and explores avenues for improvements in their stability toward the ionizing radiation. In terms of applications, we concentrate on enrichment polymer layers (EPLs), which are polymer thin films employed in sensor devices for the detection of chemical and biological substances. Specifically, we have studied the influence of gamma irradiation on nanoscale poly(glycidyl methacrylate) (PGMA) grafted EPL films. First, it was determined that a significant level of cross-linking was caused by irradiation in pure PGMA films. The cross-linking is accompanied by the formation of conjugated ester, carbon double bonds, hydroxyl groups, ketone carbonyls, and the elimination of epoxy groups as determined by FTIR. Polystyrene, 4-amino-2,2,6,6-tetramethylpiperidine 1-oxyl, dimethylphenylsilanol, BaF2, and gold nanoparticles were incorporated into the films and were found to mitigate different aspects of the radiation damage. PMID- 26259101 TI - Global SUMOylation on active chromatin is an acute heat stress response restricting transcription. AB - BACKGROUND: Cells have developed many ways to cope with external stress. One distinctive feature in acute proteotoxic stresses, such as heat shock (HS), is rapid post-translational modification of proteins by SUMOs (small ubiquitin-like modifier proteins; SUMOylation). While many of the SUMO targets are chromatin proteins, there is scarce information on chromatin binding of SUMOylated proteins in HS and the role of chromatin SUMOylation in the regulation of transcription. RESULTS: We mapped HS-induced genome-wide changes in chromatin occupancy of SUMO 2/3-modified proteins in K562 and VCaP cells using ChIP-seq. Chromatin SUMOylation was further correlated with HS-induced global changes in transcription using GRO-seq and RNA polymerase II (Pol2) ChIP-seq along with ENCODE data for K562 cells. HS induced a rapid and massive rearrangement of chromatin SUMOylation pattern: SUMOylation was gained at active promoters and enhancers associated with multiple transcription factors, including heat shock factor 1. Concomitant loss of SUMOylation occurred at inactive intergenic chromatin regions that were associated with CTCF-cohesin complex and SETDB1 methyltransferase complex. In addition, HS triggered a dynamic chromatin binding of SUMO ligase PIAS1, especially onto promoters. The HS-induced SUMOylation on chromatin was most notable at promoters of transcribed genes where it positively correlated with active transcription and Pol2 promoter-proximal pausing. Furthermore, silencing of SUMOylation machinery either by depletion of UBC9 or PIAS1 enhanced expression of HS-induced genes. CONCLUSIONS: HS-triggered SUMOylation targets promoters and enhancers of actively transcribed genes where it restricts the transcriptional activity of the HS-induced genes. PIAS1-mediated promoter SUMOylation is likely to regulate Pol2-associated factors in HS. PMID- 26259103 TI - Negative-pressure-induced enhancement in a freestanding ferroelectric. AB - Ferroelectrics are widespread in technology, being used in electronics and communications, medical diagnostics and industrial automation. However, extension of their operational temperature range and useful properties is desired. Recent developments have exploited ultrathin epitaxial films on lattice-mismatched substrates, imposing tensile or compressive biaxial strain, to enhance ferroelectric properties. Much larger hydrostatic compression can be achieved by diamond anvil cells, but hydrostatic tensile stress is regarded as unachievable. Theory and ab initio treatments predict enhanced properties for perovskite ferroelectrics under hydrostatic tensile stress. Here we report negative-pressure driven enhancement of the tetragonality, Curie temperature and spontaneous polarization in freestanding PbTiO3 nanowires, driven by stress that develops during transformation of the material from a lower-density crystal structure to the perovskite phase. This study suggests a simple route to obtain negative pressure in other materials, potentially extending their exploitable properties beyond their present levels. PMID- 26259104 TI - Eliminating degradation and uncovering ion-trapping dynamics in electrochromic WO3 thin films. AB - There is keen interest in the use of amorphous WO3 thin films as cathodic electrodes in transmittance-modulating electrochromic devices. However, these films suffer from ion-trapping-induced degradation of optical modulation and reversibility on extended Li(+)-ion exchange. Here, we demonstrate that ion trapping-induced degradation, which is commonly believed to be irreversible, can be successfully eliminated by constant-current-driven de-trapping; that is, WO3 films can be rejuvenated and regain their initial highly reversible electrochromic performance. Pronounced ion trapping occurs when x exceeds ~0.65 in LixWO3 during ion insertion. We find two main kinds of Li(+)-ion-trapping site (intermediate and deep) in WO3, where the intermediate ones are most prevalent. Li(+) ions can be completely removed from intermediate traps but are irreversibly bound in deep traps. Our results provide a general framework for developing and designing superior electrochromic materials and devices. PMID- 26259105 TI - Ferroelectrics: The positives of going negative. PMID- 26259106 TI - Identification of catalytic sites for oxygen reduction in iron- and nitrogen doped graphene materials. AB - While platinum has hitherto been the element of choice for catalysing oxygen electroreduction in acidic polymer fuel cells, tremendous progress has been reported for pyrolysed Fe-N-C materials. However, the structure of their active sites has remained elusive, delaying further advance. Here, we synthesized Fe-N-C materials quasi-free of crystallographic iron structures after argon or ammonia pyrolysis. These materials exhibit nearly identical Mossbauer spectra and identical X-ray absorption near-edge spectroscopy (XANES) spectra, revealing the same Fe-centred moieties. However, the much higher activity and basicity of NH3 pyrolysed Fe-N-C materials demonstrates that the turnover frequency of Fe-centred moieties depends on the physico-chemical properties of the support. Following a thorough XANES analysis, the detailed structures of two FeN4 porphyrinic architectures with different O2 adsorption modes were then identified. These porphyrinic moieties are not easily integrated in graphene sheets, in contrast with Fe-centred moieties assumed hitherto for pyrolysed Fe-N-C materials. These new insights open the path to bottom-up synthesis approaches and studies on site support interactions. PMID- 26259107 TI - Thermoresponsive actuation enabled by permittivity switching in an electrostatically anisotropic hydrogel. AB - Electrostatic repulsion, long used for attenuating surface friction, is not typically employed for the design of bulk structural materials. We recently developed a hydrogel with a layered structure consisting of cofacially oriented electrolyte nanosheets. Because this unusual geometry imparts a large anisotropic electrostatic repulsion to the hydrogel interior, the hydrogel resisted compression orthogonal to the sheets but readily deformed along parallel shear. Building on this concept, here we show a hydrogel actuator that operates by modulating its anisotropic electrostatics in response to changes of electrostatic permittivity associated with a lower critical solution temperature transition. In the absence of substantial water uptake and release, the distance between the nanosheets rapidly expands and contracts on heating and cooling, respectively, so that the hydrogel lengthens and shortens significantly, even in air. An L-shaped hydrogel with an oblique nanosheet configuration can thus act as a unidirectionally proceeding actuator that operates without the need for external physical biases. PMID- 26259108 TI - Novel Ordered Mesoporous Carbon Based Sulfonic Acid as an Efficient Catalyst in the Selective Dehydration of Fructose into 5-HMF: the Role of Solvent and Surface Chemistry. AB - Novel ionic liquid derived ordered mesoporous carbons functionalized with sulfonic acid groups IOMC-ArSO3H and GIOMC-ArSO3H were prepared, characterized, and examined in the dehydration reaction of fructose into 5-hydroxymethylfurfural (5-HMF) both in aqueous and nonaqueous systems. To study and correlate the surface properties of these carbocatalysts and some other SBA-15 typed solid acids with 5-HMF yield, hydrophilicity index (H-index) were employed in the fructose dehydration. Our study systematically declared that almost a criterion may be expected for application of solid acids in which by increasing H-index value up to 0.8 the HMF yield enhances accordingly. More increase in H-index up to 1.3 did not change the HMF yield profoundly. Although, it has been shown that the catalyst with larger H-index (~1.3) resulted in higher activity both in aqueous and 2-propanol systems, during the recycling process deactivation occurs because of more water uptake and the catalysts with optimum amount of H-index (~0.8) is more robust in the dehydration of fructose. PMID- 26259109 TI - Copolymerization of Propylene and Polar Monomers Using Pd/IzQO Catalysts. AB - Palladium catalysts bearing imidazo[1,5-a]quinolin-9-olate-1-ylidene (IzQO) ligands polymerize alpha-olefins while incorporating polar monomers. The steric environment provided by N-heterocyclic-carbene (NHC) enables regioselective insertion of alpha-olefins and polar monomers, yielding polypropylene, propylene/allyl carboxylate copolymers, and propylene/methyl acrylate copolymer. Known polymerization catalysts bearing NHC-based ligands decompose rapidly, whereas the present catalyst is durable because of structural confinement, wherein the NHC-plane is coplanar to the metal square plane. The present catalyst system enables facile access to a new class of functionalized polyolefins and helps conceive a new fundamental principle for designing NHC-based ligands. PMID- 26259113 TI - Comparison of the Expression and Granting of Requests for Euthanasia in Belgium in 2007 vs 2013. PMID- 26259114 TI - Quantification of Maxillary Dental Arcade Curvature and the Estimation of Biological Ancestry in Forensic Anthropology. AB - Previous studies suggest that palate shape is a useful indicator of biological ancestry in human remains. This study evaluates interobserver error in ancestry estimation using palate shape and explores palate shape variation in Gullah (descendants of West Africans) and Seminole (Indigenous American) population samples using geometric morphometric analysis. Ten participants were asked to ascribe biological ancestry and shape to 28 dental casts based on a classification scheme employed in previous studies. The mean correct classification was 42.0%, indicating that the likelihood of assigning the correct ancestry is very poor and not significantly different from random assignment (p = 0.12). The accuracy analysis based on categorical classification of the casts was complemented by geometric morphometric analysis of nine 3D landmarks reflecting palate shape of 158 casts. Principal component analysis results show no difference between populations regarding palate shape, and cross-validated discriminant function analysis correctly classified only 62.0% of the specimens. Combined, these results show that previous methods to estimate ancestry are inaccurate and that this inaccuracy is probably due to a lack of palate shape differences between groups, rather than limitation of the analytical method per se. Therefore, we recommend caution should be used when choosing to apply the analysis of palate shape in forensically relevant contexts. PMID- 26259115 TI - Preclinical evaluation of 2-amino-2-[11C]methyl-butanoic acid as a potential tumor-imaging agent in a mouse model. AB - OBJECTIVE: C-labeled 2-amino-2-methyl-butanoic acid (Iva) was previously reported to provide high tumor uptake; however, the pharmacokinetic properties of C labeled Iva have not been characterized. In the present study, we evaluated the potential of [C]Iva as a PET probe for tumor imaging. METHODS: [C]Iva was incubated in mouse serum for 60 min at 37 degrees C and then analyzed by high performance liquid chromatography and thin-layer chromatography. In-vitro cellular uptake of [C]Iva was determined in PBS and sodium-free buffer at 37 degrees C using SY human small-cell lung cancer cells. The effects of inhibitors of amino acid transporters on [C]Iva uptake were also determined in PBS. In-vivo distribution and dynamic PET studies were conducted in SY tumor-bearing mice. RESULTS: [C]Iva was stable in mouse serum in vitro for 60 min. The cellular uptake of [C]Iva was linearly increased for 20 min in both PBS and sodium-free buffer and almost completely inhibited by an inhibitor of system L amino acid transporters and another of LAT1, a transporter of system L. In-vivo distribution and dynamic PET studies showed that [C]Iva was highly accumulated in tumor, but not in normal tissues, except for the pancreas and kidneys. The [C]Iva uptake ratio of tumor to several normal tissues, such as the lung, muscle, and brain, was high. CONCLUSION: [C]Iva was stable in mouse serum and transported through system L amino acid transporters including LAT1, which is highly expressed in several tumors. [C]Iva is a promising PET probe for noninvasive tumor imaging. PMID- 26259116 TI - Facile Synthesis of Novel Heterostructure Based on SnO2 Nanorods Grown on Submicron Ni Walnut with Tunable Electromagnetic Wave Absorption Capabilities. AB - In this work, the magnetic-dielectric core-shell heterostructure composites with the core of Ni submicron spheres and the shell of SnO2 nanorods were prepared by a facile two-step route. The crystal structure and morphology were investigated by X-ray diffraction analysis, transmission electron microscopy (TEM), and field emission scanning electron microscopy (FESEM). FESEM and TEM measurements present that SnO2 nanorods were perpendicularly grown on the surfaces of Ni spheres and the density of the SnO2 nanorods could be tuned by simply varying the addition amount of Sn(2+) in this process. The morphology of Ni/SnO2 composites were also determined by the concentration of hydrochloric acid and a plausible formation mechanism of SnO2 nanorods-coated Ni spheres was proposed based on hydrochloric acid concentration dependent experiments. Ni/SnO2 composites exhibit better thermal stability than pristine Ni spheres based on thermalgravimetric analysis (TGA). The measurement on the electromagnetic (EM) parameters indicates that SnO2 nanorods can improve the impedance matching condition, which is beneficial for the improvement of electromagnetic wave absorption. When the coverage density of SnO2 nanorod is in an optimum state (diameter of 10 nm and length of about 40-50 nm), the optimal reflection loss (RL) of electromagnetic wave is -45.0 dB at 13.9 GHz and the effective bandwidth (RL below -10 dB) could reach to 3.8 GHz (12.3 16.1 GHz) with the absorber thickness of only 1.8 mm. By changing the loading density of SnO2 nanorods, the best microwave absorption state could be tuned at 1 18 GHz band. These results pave an efficient way for designing new types of high performance electromagnetic wave absorbing materials. PMID- 26259117 TI - Carbohydrate-Conjugated Amino Acid-Based Fluorescent Block Copolymers: Their Self Assembly, pH Responsiveness, and/or Lectin Recognition. AB - An effective strategy has been documented to combine both carbohydrate and amino acid biomolecules in a single synthetic polymeric system via a reversible addition-fragmentation chain transfer (RAFT) polymerization technique. The resultant unique block copolymer was engineered to form uniform micelles with the desired projection of either selective or both amino acid/sugar residues on the outer surface with multivalency, providing pH-based stimuli-responsiveness and/or lectin recognition. The self-assembly process was studied in detail by field emission scanning electron microscopy (FE-SEM), dynamic light scattering (DLS), and UV-visible spectroscopy. The enhanced lectin binding behavior was observed for glyconanoparticles with both amino acid/sugar entities on the shell as compared to the only glycopolymer nanoparticle because of the higher steric hindrance factor in the case of only the glycopolymer nanoparticle. Fluorophore conjugation by postpolymerization functionalization was further exploited by fluorescence spectroscopy for evidencing the lectin recognition process. PMID- 26259118 TI - Influence of the hospital environment and presence of the physician on the white coat effect. AB - OBJECTIVE: To determine the separate contribution of the physician and the hospital environment to differences between home (HBP) and office BP (OBP). METHODS: For 3 consecutive days, 65 hypertensive patients measured their HBP. OBP was determined with the same device by the physician. A higher OBP than HBP was regarded as white-coat effect (WCE), whereas lower OBP than HBP was regarded masked effect. OBP was measured automatically before, during and after the presence of the physician. The physician effect was the BP rise caused by the entrance of physician. The WCE minus the physician effect was regarded the hospital's contribution to the BP differences (hospital effect). We assessed the magnitudes of the hospital effect and the physician effect in determining the WCE. Furthermore, we assessed the correlation of these BP phenomena with each other, and with clinical variables. RESULTS: The WCE consisted of 4.6/-1.7 +/- 9.9/10.9 mmHg hospital effect and of 4.4/3.4 +/- 6.6/3.3 mmHg PE. The masked effect consisted of a substantially larger hospital effect (19.6/9.4 +/- 12.7/9.5 mmHg) than physician effect (4.6/3.0 +/- 6.4/3.9 mmHg). Physician effect did not correlate with systolic or diastolic WCE or masked effect (r = -0.05 to 0.08, P > 0.39). In regression analysis, age, baseline mean arterial pressure and BMI were not significantly associated with WCE (all P values >0.4). CONCLUSION: BP differences between home and office can largely be attributed to the hospital environment rather than to the entrance of the physician. The physician-related BP effect is not related to differences of HBP and OBP. PMID- 26259119 TI - Refined phenotyping identifies links between preeclampsia and related diseases in a Norwegian preeclampsia family cohort. AB - OBJECTIVE: Preeclampsia is a complex genetic disease of pregnancy with a heterogenous presentation, unknown cause and potential severe outcomes for both mother and child. Preeclamptic women have increased risk for atherothrombotic cardiovascular disease. We aimed to identify heritabilities and phenotypic correlations of preeclampsia and related conditions in the Norwegian Preeclampsia Family Biobank. METHODS: By applying a variance components model, a total of 493 individuals (from 138 families with increased occurrence of preeclampsia) were classified according to 30 disease-related phenotypes. RESULTS: Of parous women, 75.7% (263/338) had experienced preeclampsia and 35.7% of women with and 22.4% without preeclampsia delivered children small for gestational age (SGA). We identified 11 phenotypes as heritable. The increased occurrence of preeclampsia was reflected by the presence [heritability (H2r) = 0.60)] and severity (H2r = 0.15) of preeclampsia and being born in a preeclamptic pregnancy (H2r = 0.25). Other heritable phenotypes identified included SGA (H2r = 0.40), chronic hypertension (H2r = 0.57), severity of atherothrombotic cardiovascular disease (H2r = 0.31), BMI (H2r = 0.60) and pulmonary disease (H2r = 0.91). The heritable phenotype preeclampsia overlapped with SGA (P = 0.03), whereas pulmonary disease was phenotypically correlated with atherothrombotic cardiovascular disease (P < 0.01), SGA (P = 0.02) and BMI (P = 0.02). CONCLUSION: This is the first study identifying the H2r of a range of health-related conditions in preeclamptic families. Our study demonstrates how refinement of phenotypes leads to better H2r estimation and the identification of a biological relationship between preeclampsia and related traits. PMID- 26259120 TI - Health-related quality of life and blood pressure 12 months after renal denervation. AB - AIM: To examine the effect of renal denervation (RDN) on blood pressure (BP) and health-related quality of life (QoL) in patients with resistant hypertension, pseudoresistant hypertension due to a white-coat effect and in patients with uncontrolled masked hypertension. METHODS: Using the Medical Outcomes Study 36 Item Short-Form Health Survey (SF-36), Beck Depression Inventory (BDI) and Spielberger's state and trait anxiety questionnaires, we examined QoL, symptoms of depression and anxiety prior to and 12 months following RDN. BP was assessed from clinic and ambulatory blood pressure monitoring (ABPM) recordings. RESULTS: Patients with uncontrolled masked hypertension had the highest BDI and anxiety scores among all groups at baseline. Twelve months following RDN clinic and ambulatory BP were reduced only in those patients with resistant hypertension (delta SBP: clinic -16 +/- 3 mmHg, ABPMday -8 +/- 2 mmHg, ABPMnight -8 +/- 2 mmHg, all P < 0.01). Clinic BP was reduced in the pseudoresistant group (-17 +/- 6 mmHg, P < 0.01) but was elevated in the uncontrolled masked group (+13 +/- 6 mmHg, P = 0.02). In all patients, trait anxiety (P < 0.05), BDI scores (P < 0.05) and the SF-36 mental component summary (MCS) score (P < 0.001) were improved. The improvement in the SF-36 MCS was confined to those patients with resistant hypertension (+4.0 +/- 1.1, P < 0.01). The change in clinic BP after RDN was related to the baseline clinic BP (systolic: r = 0.54, P < 0.001; diastolic r = 0.43, P < 0.001), the number of ablations delivered (both clinic and mean day ABPM systolic r = 0.24, P < 0.05) and to the change in SF-36 MCS score (systolic: r = 0.25, P = 0.01; diastolic r = 0.24, P = 0.02). CONCLUSION: These results indicate that in patients with confirmed resistant hypertension, RDN is associated with a reduction in BP and a sustained improvement in mental health related aspects of QoL. PMID- 26259121 TI - Association of anxiety and depression with hypertension control: a US multidisciplinary group practice observational study. AB - OBJECTIVE: The presence of a mental health disorder with hypertension is associated with higher cardiovascular disease mortality than hypertension alone. Although earlier detection of hypertension has been demonstrated in patients with anxiety and depression, the relationship of mental health disorders to hypertension control is unknown. Our objective was to evaluate rates and predictors of incident hypertension control among patients with anxiety and/or depression compared with patients without either mental health diagnosis. METHODS: A 4-year retrospective analysis included 4362 patients, at least 18 years old, who received primary care in a large academic group practice from 2008 to 2011. Patients met The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure criteria and had a hypertension diagnosis. Kaplan-Meier analysis estimated the probability of achieving control for patients with and without anxiety and/or depression. Cox proportional hazard models were fit to identify predictors of time to control. RESULTS: Overall, 13% (n = 573) had a baseline diagnosis of anxiety and/or depression. Those with anxiety and/or depression demonstrated more primary care and specialty visits than those without either condition. After adjustment, patients with anxiety and/or depression had faster rates of hypertension control (hazard ratio [HR] 1.22; 1.07-1.39] than patients without either diagnosis. Other associations of faster hypertension control included female gender (HR 1.32; 1.20 1.44), absence of tobacco use (HR 1.17; 1.03-1.33), Medicaid use (HR 1.27; 1.09 1.49), and a higher Adjusted Clinical Group Risk Score (HR 1.13; 1.10-1.17), a measure of healthcare utilization. CONCLUSION: Greater healthcare utilization among patients with anxiety and/or depression may contribute to faster hypertension control. PMID- 26259122 TI - Concordance with DASH diet and blood pressure change: results from the Framingham Offspring Study (1991-2008). AB - BACKGROUND: Concordance with the Dietary Approaches to Stop Hypertension (DASH) diet has been shown to reduce blood pressure (BP) in short-term intervention studies, but long-term effects are unclear. We evaluated the association of DASH diet concordance with BP trajectories and incidence of hypertension, in 2187 men and women (mean age 52.5 years at baseline) participating in the Framingham Offspring cohort. METHOD: Diet and BP were assessed from 1991 to 2008, with a median follow-up time of 13.4 years. DASH scores (ranging from 0 for worst to 10 for best concordance with DASH diet) were calculated by summing 10 food components that comprise the DASH diet pattern, including fruits and vegetables, low-fat dairy products, lean meat, and plant-based protein. Mixed-effect and Cox regression models were applied, to assess the association of DASH diet concordance with BP longitudinal change and with incidence of hypertension, respectively. All analyses were adjusted for age, sex, smoking status, history of diabetes, BMI, and physical activity. RESULT: Overall, SBP increased by 0.34 mmHg and DBP by 0.10 mmHg annually, in the Framingham Offspring cohort. Every unit increase in the DASH score resulted in a modest increase in SBP of 0.054 mmHg/year (P = 0.028). No associations were observed between DASH diet concordance and DBP or incidence of hypertension. CONCLUSION: Long-term concordance with the DASH diet was not associated with a decreasing BP trajectory over time, or with decreased incidence of hypertension, in this population of middle-aged adults. PMID- 26259123 TI - Effects of passive smoking on hypertension in rural Chinese nonsmoking women. AB - BACKGROUND: Increasing evidence suggest that active smoking is a risk factor for hypertension, but little is known about the effects of passive smoking on this condition. In China, female passive smoking is widespread and severe due to the high proportion of men who smoke, particularly in rural areas. This study assessed whether passive smoking is associated with increased risk of hypertension among nonsmoking women in rural China. METHODS: A total of 392 nonsmoking women from a rural area of Shanxi Province (northern China) participated in this cross-sectional study. Data on female passive smoking, and other factors known to influence hypertension, were collected during face-to-face interviews. Logistic regression was used to evaluate the association analyses after adjusting for potential confounders. RESULTS: In total, 162 of the 392 participants were hypertensive (41.3%); 118 participants (30.1%) reported exposure to passive smoking, of whom 88.4% were exposed to smoke in the home. After adjusting for age, BMI, education, occupation, drinking status, physical activity, and menopause status, passive smoking conferred an approximately two fold risk increase of hypertension (adjusted odds ratio = 1.99, 95% confidence interval 1.16, 3.39). The adjusted odds ratios for passive smoking exposure levels of one to three, four to six, and more than six occasions per week were 1.01 (0.39-2.62), 2.57 (1.05-6.30), and 2.59 (1.18-5.69), respectively. CONCLUSION: In rural areas of northern China, female passive smoking in the home is prevalent. Frequent exposure to secondhand smoke is a risk factor for hypertension among nonsmoking women, which suggests that measures should be taken to prevent passive smoking among this population. PMID- 26259124 TI - Pulsatile and steady components of blood pressure and subclinical cerebrovascular disease: the Northern Manhattan Study. AB - OBJECTIVES: To assess whether pulse pressure (PP) is associated, independently of mean arterial pressure (MAP), with perivascular spaces (PVS), lacunar lesions presumably ischemic (LPI), and white matter hyperintensity volume (WMHV) seen on brain MRI. METHODS: Participants in the Northern Manhattan Study had their blood pressure (BP) taken during their baseline enrollment visit and again during a visit for a brain MRI a mean of 7 years later. We assessed small and large PVS, lacunar LPI, and WMHV on MRI. We examined the association of SBP, DBP, MAP, and PP at baseline with subclinical markers of cerebrovascular disease using generalized linear models and adjusting for vascular risk factors. RESULTS: Imaging and BP data were available for 1009 participants (mean age 68 +/- 8 years, 60% women, 60% Hispanic). DBP was associated with lacunar LPI and WMHV, whereas SBP was associated with small and large PVS. Using MAP and PP together disclosed that the effect size for PP was greater for large PVS, whereas the effect of MAP was greater for lacunar LPI and WMHV. The effects of DBP were flat or negative at any degree of SBP higher than 120 mmHg for small and large PVS, whereas a positive association was noted for lacunar LPI and WMHV with any DBP increase over any degree of SBP. CONCLUSION: We report here a segregated association between the pulsatile and steady components of the BP with subclinical markers of cerebrovascular disease. These differential associations may reflect the underlying disease of these biomarkers. PMID- 26259125 TI - Contribution of serotonin to cardiac remodeling associated with hypertensive diastolic ventricular dysfunction in rats. AB - OBJECTIVE: Left-ventricular hypertrophy and interstitial fibrosis are the main pathophysiological factors of heart failure with preserved ejection fraction. Blockade of the serotonin 5-HT2B receptor (5-HT2BR) has been shown to reduce cardiac hypertrophy, oxidative stress, and extracellular cell matrix activation. In this study, we evaluated the effects of the 5-HT2BR blockade, on hemodynamic and cardiac remodeling, in spontaneously hypertensive rats (SHRs) that display a diastolic dysfunction with preserved ejection fraction. METHOD: Thirty-seven-week old SHRs were randomized in four groups receiving either saline, the selective 5 HT2BR antagonist RS-127445 (1 mg/kg per day), a calcium channel blocker nicardipine (6 mg/kg per day), or RS-127445 + nicardipine. During the 14 weeks of treatment period, cardiac function and blood pressure were monitored by echocardiography and tail-cuff. Finally, electrocardiograms and invasive hemodynamics were obtained before blood collection. Heart was analyzed for morphology and mRNA expression. A complementary study evaluated the cardiac and vascular effects of serotonin on wild-type and mice knockout for the 5-HT2BR (Htr2B) and/or the 5-HT2AR (Htr2A). RESULTS: Despite the left ventricular 5-HT2BR overexpression, 5-HT2BR blockade by RS-127445 did not affect left ventricular hypertrophy and fibrosis in SHRs. This antagonist did not improve diastolic dysfunction, neither alone nor in combination with nicardipine, although it induced plasma brain natriuretic peptide decrease. Moreover, RS-127445 amplified subendocardial fibrosis and favored left ventricular dilatation. Finally, a subendocardial left ventricular fibrosis was induced by chronic serotonin in wild type mice, which was increased in Htr2B animals, but prevented in Htr2A and Htr2A/2B mice, and could be explained by a contribution of the endothelial 5 HT2BRs to coronary vasodilatation. CONCLUSION: This work is the first to identify a cardioprotective function of the 5-HT2BR in an integrated model of diastolic dysfunction with preserved ejection fraction. PMID- 26259126 TI - Magnetic zirconium hexacyanoferrate(II) nanoparticle as tracing tag for electrochemical DNA assay. AB - Novel multifunctional magnetic zirconium hexacyanoferrate nanoparticles (ZrHCF MNPs) were prepared, which consisted of magnetic beads (MBs) inner core and zirconium hexacyanoferrate(II) (ZrHCF) outer shell. As an artificial peroxidase, the ZrHCF MNPs exhibited remarkable electrocatalytic properties in the reduction of H2O2 at 0.2 V vs saturated calomel electrode (SCE). On the basis of the bonding interaction between Zr (IV) of the shell ZrHCF framework and phosphonate groups, the 5'-phosphorylated ssDNA probes with a consecutive stretch of guanines as a spacer could be incorporated in ZrHCF MNPs easily. Thus, DNA-grafted ZrHCF MNPs could be simply obtained by magnetic separation. The prepared nanoelectrocatalyst was further used as signal nanoprobe for the ultrasensitive electrochemical DNA assay. Under optimal conditions, the proposed biosensor presents high sensitivity for detecting target DNA with a linear range from 1.0 fM to 1.0 nM and a low detection limit of 0.43 fM. Moreover, it exhibits good performance with excellent selectivity, high stability, and acceptable fabrication reproducibility. PMID- 26259127 TI - Cell-Mediated Dexamethasone Release from Semi-IPNs Stimulates Osteogenic Differentiation of Encapsulated Mesenchymal Stem Cells. AB - Scaffold-based delivery of bioactive molecules capable of directing stem cell differentiation is critical to the development of point-of-care cell therapy for orthopedic repair. Dexamethasone-conjugated hyaluronic acid (HA-DXM) was synthesized and combined with hydrolytically degradable, photo-cross-linkable PEG bis(2-acryloyloxy propanoate) (PEG-bis-AP) to form semi-IPNs. Dexamethasone (DX) release was limited in physiological buffer and substantially increased in the presence of encapsulated human mesenchymal stem cells (hMSCs) or exogenous hyaluronidase, confirming that release occurred primarily by a cell-mediated enzymatic mechanism. hMSCs encapsulated in PEG-bis-AP/HA-DXM semi-IPNs increased osteoblast-specific gene expression, alkaline phosphatase activity, and matrix mineralization, attaining levels that were not significantly different from positive controls consisting of hMSCs in PEG-bis-AP/native HA cultured with DX supplementation in the culture medium. These studies demonstrate that PEG-bis AP/HA-DXM semi-IPNs can provide cell-mediated release of bioactive free DX that induces hMSC osteogenic differentiation. This approach offers an efficient system for local delivery of osteogenic molecules empowering point of care applications. PMID- 26259129 TI - Origins and development of mirroring mechanisms: A neuroconstructivist framework. AB - The current review examines models developed to answer questions about the origins and early developmental processes determining the emergence of mirroring mechanisms and considers the debate about the role of the motor system in action understanding. Strengths and points of criticism deriving from existing alternative positions are illustrated. Particular emphasis is put on the neuroconstructivist framework with the aim of evaluating whether the hypotheses driven by this approach are in line with the available evidence. Within the neuroconstructivist framework, a novel model is proposed in which the direct matching and action reconstruction viewpoints on action understanding processes can be integrated by assuming a developmental perspective. It is suggested that mirroring mechanisms are shaped by a domain-relevant narrowing process driven by sensorimotor experience and that action understanding can take advantage of both top-down and bottom-up processes, in a multilevel and dynamic fashion. PMID- 26259128 TI - Estimates of foodborne illness-related hospitalizations and deaths in Canada for 30 specified pathogens and unspecified agents. AB - Foodborne illness estimates help to set food safety priorities and create public health policies. The Public Health Agency of Canada estimates that 4 million episodes of foodborne illness occur each year in Canada due to 30 known pathogens and unspecified agents. The main objective of this study was to estimate the number of domestically acquired foodborne illness-related hospitalizations and deaths. Using the estimates of foodborne illness for Canada along with data from the Canadian Hospitalization Morbidity Database (for years 2000-2010) and relevant international literature, the number of hospitalizations and deaths for 30 pathogens and unspecified agents were calculated. Analysis accounted for under reporting and underdiagnosis. Estimates of the proportion foodborne and the proportion travel-related were incorporated for each pathogen. Monte Carlo simulations were performed to account for uncertainty generating mean estimates and 90% probability intervals. It is estimated that each year there are 4000 hospitalizations (range 3200-4800) and 105 (range 75-139) deaths associated with domestically acquired foodborne illness related to 30 known pathogens and 7600 (range 5900-9650) hospitalizations and 133 (range 77-192) deaths associated with unspecified agents, for a total estimate of 11,600 (range 9250-14,150) hospitalizations and 238 (range 155-323) deaths associated with domestically acquired foodborne illness in Canada. Key pathogens associated with these hospitalizations or deaths include norovirus, nontyphoidal Salmonella spp., Campylobacter spp., VTEC O157 and Listeria monocytogenes. This is the first time Canada has established pathogen-specific estimates of domestically acquired foodborne illness-related hospitalizations and deaths. This information illustrates the substantial burden of foodborne illness in Canada. PMID- 26259130 TI - Efficacy of sugammadex in rocuronium-induced or antibiotic-induced anaphylaxis. A case-control study. AB - We report 13 cases of presumed rocuronium-induced anaphylaxis in which sugammadex was administered with the intention of reversing the immunological reaction. Of these 13 cases, eight (62%) were later confirmed to be type-1 hypersensitivity reactions to rocuronium, three (23%) were triggered by an antibiotic and two (15%) were non-immunologically mediated. Response to treatment was scored by the treating anaesthetist, and compared with haemodynamic and inotrope measurements from the resuscitation and anaesthetic records. Haemodynamic improvement was seen in only six (46%) cases, three of which were associated with a non-rocuronium trigger. Of the three cases in which the treating anaesthetist thought that sugammadex had been beneficial, one was not caused by rocuronium, one had no improvement in blood pressure and one required 8.5 times as much adrenaline in boluses after, compared with the period before, sugammadex administration. These data suggest that sugammadex does not modify the clinical course of a suspected hypersensitivity reaction. PMID- 26259131 TI - Expanding the Clinical Spectrum Associated With GLIS3 Mutations. AB - CONTEXT: GLIS3 (GLI-similar 3) is a member of the GLI-similar zinc finger protein family encoding for a nuclear protein with 5 C2H2-type zinc finger domains. The protein is expressed early in embryogenesis and plays a critical role as both a repressor and activator of transcription. Human GLIS3 mutations are extremely rare. OBJECTIVE: The purpose of this article was determine the phenotypic presentation of 12 patients with a variety of GLIS3 mutations. METHODS: GLIS3 gene mutations were sought by PCR amplification and sequence analysis of exons 1 to 11. Clinical information was provided by the referring clinicians and subsequently using a questionnaire circulated to gain further information. RESULTS: We report the first case of a patient with a compound heterozygous mutation in GLIS3 who did not present with congenital hypothyroidism. All patients presented with neonatal diabetes with a range of insulin sensitivities. Thyroid disease varied among patients. Hepatic and renal disease was common with liver dysfunction ranging from hepatitis to cirrhosis; cystic dysplasia was the most common renal manifestation. We describe new presenting features in patients with GLIS3 mutations, including craniosynostosis, hiatus hernia, atrial septal defect, splenic cyst, and choanal atresia and confirm further cases with sensorineural deafness and exocrine pancreatic insufficiency. CONCLUSION: We report new findings within the GLIS3 phenotype, further extending the spectrum of abnormalities associated with GLIS3 mutations and providing novel insights into the role of GLIS3 in human physiological development. All but 2 of the patients within our cohort are still alive, and we describe the first patient to live to adulthood with a GLIS3 mutation, suggesting that even patients with a severe GLIS3 phenotype may have a longer life expectancy than originally described. PMID- 26259132 TI - Plasma DPP4 Activities Are Associated With Osteoporosis in Postmenopausal Women With Normal Glucose Tolerance. AB - CONTEXT: Inflammation, insulin resistance, dyslipidemia, and glucagon-like peptide-1 (GLP-1) are risk factors for osteoporosis. Dipeptidyl peptidase-4 (DPP4) is a newly identified adipokine related to these risk factors. OBJECTIVE: To investigate the association between plasma DPP4 activities and osteoporosis. DESIGN, SETTING, AND PATIENTS: This was a cross-sectional study conducted in Guilin, China. A total of 744 postmenopausal women with normal glucose tolerance were studied. MAIN OUTCOME MEASURES: Plasma DPP4 activity, inflammatory markers, blood lipids, homeostatic model assessment of insulin resistance (HOMA-IR), active GLP-1, bone turnover markers, and bone mineral density (BMD) were measured in all participants. RESULTS: Participants in the highest quartile of DPP4 activity had higher triglyceride, total cholesterol, HOMA-IR, IL-6, high sensitivity C-reactive protein (hs-CRP), C-terminal telopeptide of type I collagen, and osteocalcin and lower BMD (lumbar spine and femoral neck) and active GLP-1 compared with participants in the lowest quartile (P < .05). DPP4 activities were associated positively with triglyceride, total cholesterol, HOMA IR, IL-6, hs-CRP, C-terminal telopeptide of type I collagen, and osteocalcin and negatively with active GLP-1 and BMD (P < .05). In the highest DPP4 quartile, osteoporosis risk was significantly higher (odds ratio, 3.01; 95% confidence interval, 1.66-5.43) than in the lowest quartile after adjustment for potential confounders. The risk for osteoporosis increased more with higher levels of DPP4 activity, HOMA-IR, IL-6, and hs-CRP (P < .05), but not with higher levels of triglyceride and total cholesterol or lower levels of active GLP-1. CONCLUSIONS: This study shows that increased DPP4 activities are independently associated with osteoporosis. The mechanisms may be partly explained by the effect of DPP4 on inflammation and insulin resistance. PMID- 26259133 TI - Macronutrient Regulation of Ghrelin and Peptide YY in Pediatric Obesity and Prader-Willi Syndrome. AB - BACKGROUND: The roles of macronutrients and GH in the regulation of food intake in pediatric obesity and Prader-Willi Syndrome (PWS) are poorly understood. OBJECTIVE: We compared effects of high-carbohydrate (HC) and high-fat (HF) meals and GH therapy on ghrelin, insulin, peptide YY (PYY), and insulin sensitivity in children with PWS and body mass index (BMI) -matched obese controls (OCs). METHODS: In a randomized, crossover study, 14 PWS (median, 11.35 y; BMI z score [BMI-z], 2.15) and 14 OCs (median, 11.97 y; BMI-z, 2.35) received isocaloric breakfast meals (HC or HF) on separate days. Blood samples were drawn at baseline and every 30 minutes for 4 hours. Mixed linear models were adjusted for age, sex, and BMI-z. RESULTS: Relative to OCs, children with PWS had lower fasting insulin and higher fasting ghrelin and ghrelin/PYY. Ghrelin levels were higher in PWS across all postprandial time points (P < .0001). Carbohydrate was more potent than fat in suppressing ghrelin levels in PWS (P = .028); HC and HF were equipotent in OCs but less potent than in PWS (P = .011). The increase in PYY following HF was attenuated in PWS (P = .037); thus, postprandial ghrelin/PYY remained higher throughout. A lesser increase in insulin and lesser decrease in ghrelin were observed in GH-treated PWS patients than in untreated patients; PYY responses were comparable. CONCLUSION: Children with PWS have fasting and postprandial hyperghrelinemia and an attenuated PYY response to fat, yielding a high ghrelin/PYY ratio. GH therapy in PWS is associated with increased insulin sensitivity and lesser postprandial suppression of ghrelin. The ratio Ghrelin/PYY may be a novel marker of orexigenic drive. PMID- 26259134 TI - Metabolic Health in Short Children Born Small for Gestational Age Treated With Growth Hormone and Gonadotropin-Releasing Hormone Analog: Results of a Randomized, Dose-Response Trial. AB - CONTEXT: Previously we showed that pubertal children born small for gestational age (SGA) with a poor adult height (AH) expectation can benefit from treatment with GH 1 mg/m(2) per day (~ 0.033 mg/kg/d) in combination with 2 years of GnRH analog (GnRHa) and even more so with a double GH dose. GnRHa treatment is thought to have negative effects on body composition and blood pressure. Long-term effects and GH-dose effects on metabolic health in children treated with combined GH/GnRHa are unknown. OBJECTIVE: This study aimed to investigate body composition, blood pressure, and lipid profile during GH treatment, either with or without 2 years of additional GnRHa. To assess whether GH 2 mg/m(2) per day (~ 0.067 mg/kg/d) results in a similar or even more favorable metabolic health at AH than GH 1 mg/m(2) per day. METHODS: This was a longitudinal, randomized, dose response GH trial involving 107 short SGA children (58 girls) treated with GH until AH (GH randomized 1 or 2 mg/m(2)/d during puberty). Sixty-four children received additional GnRHa. At AH, metabolic parameters were compared between children treated with combined GH/GnRHa and those with only GH. The GH dose effect on metabolic health was evaluated in a subgroup of 47 children who started GH treatment in early puberty (randomized 1 or 2 mg/m(2)/d) with 2 years of GnRHa. RESULTS: At AH, fat mass percentage (FM%) SD score (SDS), lean body mass (LBM) SDS, blood pressure SDS, and lipid profile were similar between children treated with combined GH/GnRHa and those with only GH. In the pubertal subgroup, FM% SDS was lower during treatment with GH 2 mg/m(2) per day. There was no GH dose-dependent effect on LBM SDS, blood pressure, and lipid profile. CONCLUSIONS: Combined GH/GnRHa treatment has no long-term negative effects on metabolic health compared with only GH. Started in early puberty, a GH dose of 2 mg/m(2) per day results in a similar metabolic health at AH and a more favorable FM% than GH 1 mg/m(2) per day. PMID- 26259135 TI - Succinate Dehydrogenase (SDH)-Deficient Pancreatic Neuroendocrine Tumor Expands the SDH-Related Tumor Spectrum. AB - CONTEXT: Mutations in genes encoding the subunits of succinate dehydrogenase (SDH) can lead to pheochromocytoma/paraganglioma formation. However, SDH mutations have also been linked to nonparaganglionic tumors. OBJECTIVE: The objective was to investigate which nonparaganglionic tumors belong to the SDH associated tumor spectrum. DESIGN: This was a retrospective cohort study. SETTING: The setting was a tertiary referral center. PATIENTS: Patients included all consecutive SDHA/SDHB/SDHC and SDHD mutation carriers followed at the Department of Endocrinology of the Leiden University Medical Center who were affected by non-pheochromocytoma/paraganglioma solid tumors. MAIN OUTCOME MEASURES: Main outcome measures were SDHA/SDHB immunohistochemistry, mutation analysis, and loss of heterozygosity analysis of the involved SDH-encoding genes. RESULTS: Twenty-five of 35 tumors (from 26 patients) showed positive staining on SDHB and SDHA immunohistochemistry. Eight tumors showed negative staining for SDHB and positive staining for SDHA: a pancreatic neuroendocrine tumor, a macroprolactinoma, two gastric gastrointestinal stromal tumors, an abdominal ganglioneuroma, and three renal cell carcinomas. With the exception of the abdominal ganglioneuroma, loss of heterozygosity was detected in all tumors. A prolactinoma in a patient with a germline SDHA mutation was the only tumor immunonegative for both SDHA and SDHB. Sanger sequencing of this tumor revealed a somatic mutation (p.D38V) as a likely second hit leading to biallelic inactivation of SDHA. One tumor (breast cancer) showed heterogeneous SDHB staining, positive SDHA staining, and retention of heterozygosity. CONCLUSIONS: This study strengthens the etiological association of SDH genes with pituitary neoplasia, renal tumorigenesis, and gastric gastrointestinal stromal tumors. Furthermore, our results indicate that pancreatic neuroendocrine tumor also falls within the SDH-related tumor spectrum. PMID- 26259136 TI - Contact Allergy in Danish Healthcare Workers: A Retrospective Matched Case control Study. AB - Contact dermatitis in healthcare workers is a world wide problem. We conducted a retrospective observational study of the patch-test results of 1402 healthcare workers and 1402 matched controls with contact dermatitis who were treated at 3 hospitals departments in Denmark between 2007 and 2014. The primary objective was to determine whether healthcare work was associated with contact allergy to thiuram mix. Unadjusted univariate analyses revealed that healthcare work was significantly associated with occupational contact dermatitis and hand dermatitis. Contact allergy to thiuram mix was more common in healthcare workers was significantly associated with having occupational contact dermatitis, hand dermatitis and older age. In conclusion, we report here a potential problem of contact allergy to thiurams in healthcare workers with contact dermatitis. Legislative authorities may in the future focus on the use of rubber accelerators in, for example, protective gloves, which are widely used by healthcare professionals. PMID- 26259137 TI - Influence of Tracheal Obstruction on the Efficacy of Superimposed High-frequency Jet Ventilation and Single-frequency Jet Ventilation. AB - BACKGROUND: Both superimposed high-frequency jet ventilation (SHFJV) and single frequency (high-frequency) jet ventilation (HFJV) have been used with success for airway surgery, but SHFJV has been found to provide higher lung volumes and better gas exchange than HFJV in unobstructed airways. The authors systematically compared the ventilation efficacy of SHFJV and HFJV at different ventilation frequencies in a model of tracheal obstruction and describe the frequency and obstruction dependence of SHFJV efficacy. METHODS: Ten anesthetized animals (weight 25 to 31.5 kg) were alternately ventilated with SHFJV and HFJV at a set of different fHF from 50 to 600 min. Obstruction was created by insertion of interchangeable stents with ID 2 to 8 mm into the trachea. Chest wall volume was measured using optoelectronic plethysmography, airway pressures were recorded, and blood gases were analyzed repeatedly. RESULTS: SHFJV provided greater than 1.6 times higher end-expiratory chest wall volume than HFJV, and tidal volume (VT) was always greater than 200 ml with SHFJV. Increase of fHF from 50 to 600 min during HFJV resulted in a more than 30-fold VT decrease from 112 ml (97 to 130 ml) to negligible values and resulted in severe hypoxia and hypercapnia. During SHFJV, stent ID reduction from 8 to 2 mm increased end-expiratory chest wall volume by up to 3 times from approximately 100 to 300 ml and decreased VT by up to 4.2 times from approximately 470 to 110 ml. Oxygenation and ventilation were acceptable for 4 mm ID or more, but hypercapnia occurred with the 2 mm stent. CONCLUSION: In this in vivo porcine model of variable severe tracheal stenosis, SHFJV effectively increased lung volumes and maintained gas exchange and may be advantageous in severe airway obstruction. PMID- 26259138 TI - Efficacy of Superimposed High-frequency Jet Ventilation Applied to Variable Degrees of Tracheal Stenosis: One Step Forward to Optimized Patient Care. PMID- 26259140 TI - Diagnostic Accuracy of Respiratory Distress Observation Scales as Surrogates of Dyspnea Self-report in Intensive Care Unit Patients. AB - BACKGROUND: Dyspnea, like pain, can cause major suffering in intensive care unit (ICU) patients. Its evaluation relies on self-report; hence, the risk of being overlooked when verbal communication is impaired. Observation scales incorporating respiratory and behavioral signs (respiratory distress observation scales [RDOS]) can provide surrogates of dyspnea self-report in similar clinical contexts (palliative care). METHODS: The authors prospectively studied (single center, 16-bed ICU, large university hospital) 220 communicating ICU patients (derivation cohort, 120 patients; separate validation cohort, 100 patients). Dyspnea was assessed by dyspnea visual analog scale (D-VAS) and RDOS calculated from its eight components (heart rate, respiratory rate, nonpurposeful movements, neck muscle use during inspiration, abdominal paradox, end-expiratory grunting, nasal flaring, and facial expression of fear). An iterative principal component analysis and partial least square regression process aimed at identifying an optimized D-VAS correlate (intensive care RDOS [IC-RDOS]). RESULTS: In the derivation cohort, RDOS significantly correlated with D-VAS (r = 0.43; 95% CI, 0.29 to 0.58). A five-item IC-RDOS (heart rate, neck muscle use during inspiration, abdominal paradox, facial expression of fear, and supplemental oxygen) significantly better correlated with D-VAS (r = 0.61; 95% CI, 0.50 to 0.72). The median area under the receiver operating curve of IC-RDOS to predict D VAS was 0.83 (interquartile range, 0.81 to 0.84). An IC-RDOS of 2.4 predicted D VAS of 4 or greater with equal sensitivity and specificity (72%); an IC-RDOS of 6.3 predicted D-VAS of 4 or greater with 100% specificity. Similar results were found in the validation cohort. CONCLUSIONS: Combinations of observable signs correlate with dyspnea in communicating ICU patients. Future studies in noncommunicating patients will be needed to determine the responsiveness to therapeutic interventions and clinical usefulness. PMID- 26259139 TI - MicroRNA-21 Mediates Isoflurane-induced Cardioprotection against Ischemia Reperfusion Injury via Akt/Nitric Oxide Synthase/Mitochondrial Permeability Transition Pore Pathway. AB - BACKGROUND: The role of microRNA-21 in isoflurane-induced cardioprotection is unknown. The authors addressed this issue by using microRNA-21 knockout mice and explored the underlying mechanisms. METHODS: C57BL/6 and microRNA-21 knockout mice were echocardiographically examined. Mouse hearts underwent 30 min of ischemia followed by 2 h of reperfusion in vivo or ex vivo in the presence or absence of 1.0 minimum alveolar concentration of isoflurane administered before ischemia. Cardiac Akt, endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) proteins were determined by Western blot analysis. Opening of the mitochondrial permeability transition pore (mPTP) in cardiomyocytes was induced by photoexcitation-generated oxidative stress and detected by rapid dissipation of tetramethylrhodamine ethyl ester fluorescence using a confocal microscope. RESULTS: Genetic disruption of miR-21 gene did not alter phenotype of the left ventricle, baseline cardiac function, area at risk, and the ratios of phosphorylated-Akt/Akt, phosphorylated-eNOS/eNOS, and phosphorylated-nNOS/nNOS. Isoflurane decreased infarct size from 54 +/- 10% in control to 36 +/- 10% (P < 0.05, n = 8 mice per group), improved cardiac function after reperfusion, and increased the ratios of phosphorylated-Akt/AKT, phosphorylated-eNOS/eNOS, and phosphorylated-nNOS/nNOS in C57BL/6 mice subjected to ischemia-reperfusion injury. These beneficial effects of isoflurane were lost in microRNA-21 knockout mice. There were no significant differences in time of the mPTP opening induced by photoexcitation-generated oxidative stress in cardiomyocytes isolated between C57BL/6 and microRNA-21 knockout mice. Isoflurane significantly delayed mPTP opening in cardiomyocytes from C57BL/6 but not from microRNA-21 knockout mice. CONCLUSIONS: Isoflurane protects mouse hearts from ischemia-reperfusion injury by a microRNA-21-dependent mechanism. The Akt/NOS/mPTP pathway is involved in the microRNA-21-mediated protective effect of isoflurane. PMID- 26259141 TI - Epigenetics: The Epicenter for Future Anesthesia Research? PMID- 26259142 TI - Preschool irritability predicts child psychopathology, functional impairment, and service use at age nine. AB - BACKGROUND: Little is known about the predictive validity and clinical significance of chronic irritability during early childhood. This prospective, longitudinal study examined associations of preschool chronic irritability with psychiatric disorders, functional impairment, and service use at age nine in a large community sample. METHODS: Four hundred and forty-six children were assessed at age three and again at age nine. Child psychopathology and functional impairment were assessed at age three with the Preschool Age Psychiatric Assessment (PAPA) with parents and at age nine with the Kiddie-Schedule of Affective Disorders and Schizophrenia (K-SADS) with parents and children. Items from the PAPA were used to create a dimensional measure of chronic irritability at age three. At age nine, mothers, fathers, and youth completed the Child Depression Inventory (CDI) and the Screen for Anxiety Related Disorders (SCARED). RESULTS: Chronic irritability at age three predicted any current and lifetime anxiety disorders at age nine, current and lifetime generalized anxiety disorder, and current separation anxiety, after controlling for baseline anxiety disorders. In addition, preschool irritability predicted increases in anxiety and disruptive behavior disorder symptoms on the K-SADS, and maternal and paternal reports of depressive and anxiety symptoms on the CDI and SCARED. Lastly, preschool irritability predicted greater functional impairment and outpatient treatment use, even after controlling for all psychiatric disorders at baseline. CONCLUSIONS: Findings underscore the central role of irritability in developmental psychopathology and support the importance of early detection and interventions targeting preschool irritability. PMID- 26259143 TI - Integrated Medical-Behavioral Care Compared With Usual Primary Care for Child and Adolescent Behavioral Health: A Meta-analysis. AB - IMPORTANCE: Recent health care legislation and shifting health care financing strategies are transforming health and behavioral health care in the United States and incentivizing integrated medical-behavioral health care as a strategy for improving access to high-quality care for behavioral health conditions, enhancing patient outcomes, and containing costs. OBJECTIVE: To conduct a systematic meta-analysis of randomized clinical trials to evaluate whether integrated medical-behavioral health care for children and adolescents leads to improved behavioral health outcomes compared with usual primary care. DATA SOURCES: Search of the PubMed, MEDLINE, PsycINFO, and Cochrane Library databases from January 1, 1960, through December 31, 2014, yielded 6792 studies, of which 31 studies with 35 intervention-control comparisons and 13,129 participants met the study eligibility criteria. STUDY SELECTION: We included randomized clinical trials that evaluated integrated behavioral health and primary medical care in children and adolescents compared with usual care in primary care settings that met prespecified methodologic quality criteria. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened citations and extracted data, with raw data used when possible. Magnitude and direction of effect sizes were calculated. MAIN OUTCOMES AND MEASURES: Meta-analysis with a random effects model were conducted to examine an overall effect across all trials, and within intervention and prevention trials. Subsequent moderator analyses for intervention trials explored the relative effects of integrated care type on behavioral health outcomes. RESULTS: Meta-analysis with a random-effects model indicated a significant advantage for integrated care interventions relative to usual care on behavioral health outcomes (d = 0.32; 95% CI, 0.21-0.44; P < .001). Moderator analyses indicated larger effects for treatment trials that targeted diagnoses and/or elevated symptoms (d = 0.42; 95% CI, 0.29-0.55; P < .001) relative to prevention trials (d = 0.07; 95% CI, -0.13 to 0.28; P = .49). The probability was 66% that a randomly selected youth would have a better outcome after receiving integrated medical-behavioral treatment than a randomly selected youth after receiving usual care. The strongest effects were seen for treatment interventions that targeted mental health problems and those that used collaborative care models. CONCLUSIONS AND RELEVANCE: Our results, demonstrating the benefits of integrated medical behavioral primary care for improving youth behavioral health outcomes, enhance confidence that the increased incentives for integrated health and behavioral health care in the US health care system will yield improvements in the health of children and adolescents. PMID- 26259144 TI - A novel multitarget tracking algorithm for Myosin VI protein molecules on actin filaments in TIRFM sequences. AB - We propose a novel multitarget tracking framework for Myosin VI protein molecules in total internal reflection fluorescence microscopy sequences which integrates an extended Hungarian algorithm with an interacting multiple model filter. The extended Hungarian algorithm, which is a linear assignment problem based method, helps to solve measurement assignment and spot association problems commonly encountered when dealing with multiple targets, although a two-motion model interacting multiple model filter increases the tracking accuracy by modelling the nonlinear dynamics of Myosin VI protein molecules on actin filaments. The evaluation of our tracking framework is conducted on both real and synthetic total internal reflection fluorescence microscopy sequences. The results show that the framework achieves higher tracking accuracies compared to the state-of the-art tracking methods, especially for sequences with high spot density. PMID- 26259145 TI - Oroxylin A regulates glucose metabolism in response to hypoxic stress with the involvement of Hypoxia-inducible factor-1 in human hepatoma HepG2 cells. AB - Metabolic alteration in cancer cells is one of the most conspicuous characteristics that distinguish cancer cells from normal cells. In this study, we investigated the influence and signaling ways of oroxylin A affecting cancer cell energy metabolism under hypoxia. The data showed that oroxylin A remarkably reduced the generation of lactate and glucose uptake under hypoxia in HepG2 cells. Moreover, oroxylin A inhibited HIF-1alpha expression and its stability. The downstream targets (PDK1, LDHA, and HK II), as well as their mRNA levels were also suppressed by oroxylin A under hypoxia. The silencing or the overexpression of HIF-1alpha assays suggested that HIF-1alpha is required for metabolic effect of oroxylin A in HepG2 cells during hypoxia. Furthermore, oroxylin A could reduce the expression of complex III in mitochondrial respiratory chain, and then decrease the accumulation of ROS at moderate concentrations (0-50 uM) under hypoxia, which was benefit for its inhibition on glycolytic activity by decreasing ROS-mediated HIF-1 expression. Besides, oroxylin A didn't cause the loss of MMP under hypoxia and had no obvious effects on the expression of OXPHOS complexes, suggesting that oroxylin A did not affect mitochondrial mass at the moderate stress of oroxylin A. The suppressive effect of oroxylin A on glycolysis led to a significantly repress of ATP generation, for ATP generation mostly depends on glycolysis in HepG2 cells. This study revealed a new aspect of glucose metabolism regulation of oroxylin A under hypoxia, which may contribute to its new anticancer mechanism. (c) 2015 Wiley Periodicals, Inc. PMID- 26259147 TI - Summaries for patients. Cardiovascular and Cerebrovascular Mortality Are Increased in Ankylosing Spondylitis. PMID- 26259146 TI - The chromatin remodeller RSF1 is essential for PLK1 deposition and function at mitotic kinetochores. AB - Accumulation of PLK1 at kinetochores is essential for chromosome alignment and segregation; however, the mechanism underlying PLK1 recruitment to kinetochores remains unresolved. The chromatin remodeller RSF1 tightly associates with centromere proteins, but its mitotic function is unknown. Here we show that RSF1 localizes at mitotic kinetochores and directly binds PLK1. RSF1 depletion disrupts localization of PLK1 at kinetochores; the C-terminal fragment of RSF1, which can bind PLK1, is sufficient to restore PLK1 localization. Moreover, CDK1 phosphorylates RSF1 at Ser1375, and this phosphorylation is necessary for PLK1 recruitment. Subsequently, PLK1 phosphorylates RSF1 at Ser1359, stabilizing PLK1 deposition. Importantly, RSF1 depletion mimicks the chromosome misalignment phenotype resulting from PLK1 knockdown; these defects are rescued by RSF1 S1375D or RSF1 S1359D but not RSF1 S1375A, showing a functional link between phosphorylation of RSF1 and chromosome alignment. Together, these data show that RSF1 is an essential centromeric component that recruits PLK1 to kinetochores and plays a crucial role in faithful cell division. PMID- 26259149 TI - Electrophysiological evidence of phonetic normalization across coarticulation in infants. AB - The auditory neural representations of infants can easily be studied with electroencephalography using mismatch experimental designs. We recorded high density event-related potentials while 3-month-old infants were listening to trials consisting of CV syllables produced with different vowels (/bX/ or /gX/). The consonant remained the same for the first three syllables, followed (or not) by a change in the fourth position. A consonant change evoked a significant difference around the second auditory peak (400-600 ms) relative to control trials. This mismatch response demonstrates that the infants robustly categorized the consonant despite coarticulation that blurs the phonetic cues, and at an age at which they do not produce these consonants themselves. This response was obtained even when infants had no visual articulatory information to help them to track the consonant repetition. In combination with previous studies establishing categorical perception and normalization across speakers, this result demonstrates that preverbal infants already have abstract phonetic representation integrating over acoustical features in the first months of life. PMID- 26259148 TI - Musculoskeletal disorders of the hand in type 2 diabetes mellitus: prevalence and its associated factors. AB - AIM: To assess the prevalence of musculoskeletal disorders of the hand among adult patients with type 2 diabetes mellitus (T2DM) and their relation to disease duration, glycemic control and microvascular complications. METHODS: A cross sectional study was conducted at the National Center for Diabetes, Endocrinology and Genetics in Amman, Jordan. RESULTS: One thousand patients with T2DM were included in this study (mean age 57.8 +/- 9.5 years, 52.2% females and 47.8% males). Hand disorders were seen in 69.5% of patients, limited joint mobility (LJM) was the most prevalent (63.1%) condition followed by Dupuytren's contracture (DC) (18.6%). Trigger finger, thick skin and carpal tunnel syndrome (CTS) were found in 7.2%, 6.2% and 5.5% of patients, respectively. One disorder was seen in 45.4% of patients, two in18.2%, three in 4.9%, four in 0.9%, while only 0.1% of patients had all disorders. Female gender, age over 60 years and long duration of diabetes were associated with hand abnormalities. Hypertension was significantly associated with DC while retinopathy was associated with increased odds of thick skin, DC and CTS with P-values 0.037, < 0.005 and 0.002, respectively. CONCLUSION: Hand disorders are very common in T2DM. Female gender, old age, duration of diabetes, retinopathy and hypertension were significantly associated with hand disorders in T2DM. PMID- 26259150 TI - Near-Optimal Controller for Nonlinear Continuous-Time Systems With Unknown Dynamics Using Policy Iteration. AB - This paper presents a single-network adaptive critic-based controller for continuous-time systems with unknown dynamics in a policy iteration (PI) framework. It is assumed that the unknown dynamics can be estimated using the Takagi-Sugeno-Kang fuzzy model with arbitrary precision. The successful implementation of a PI scheme depends on the effective learning of critic network parameters. Network parameters must stabilize the system in each iteration in addition to approximating the critic and the cost. It is found that the critic updates according to the Hamilton-Jacobi-Bellman formulation sometimes lead to the instability of the closed-loop systems. In the proposed work, a novel critic network parameter update scheme is adopted, which not only approximates the critic at current iteration but also provides feasible solutions that keep the policy stable in the next step of training by combining a Lyapunov-based linear matrix inequalities approach with PI. The critic modeling technique presented here is the first of its kind to address this issue. Though multiple literature exists discussing the convergence of PI, however, to the best of our knowledge, there exists no literature, which focuses on the effect of critic network parameters on the convergence. Computational complexity in the proposed algorithm is reduced to the order of (Fz)(n-1) , where n is the fuzzy state dimensionality and Fz is the number of fuzzy zones in the states space. A genetic algorithm toolbox of MATLAB is used for searching stable parameters while minimizing the training error. The proposed algorithm also provides a way to solve for the initial stable control policy in the PI scheme. The algorithm is validated through real-time experiment on a commercial robotic manipulator. Results show that the algorithm successfully finds stable critic network parameters in real time for a highly nonlinear system. PMID- 26259152 TI - The Homicide-Suicide Phenomenon: Findings of Psychological Autopsies. AB - Homicide-suicide represents a single episode of violence which may decimate an entire family. This study aimed to further describe motives and context of these tragedies. Psychological autopsies were completed for 18 homicide-suicide cases in Dallas, Texas. This included postevent interviews with surviving family members and review of police and coroner records. Two-thirds of perpetrators had made either verbal or written threats prior to the homicide-suicide. A simplified typology describing victim-perpetrator relationship and motive type is suggested for future studies and clinical ease. Two-thirds of perpetrators fell into the category of Intimate-Possessive, most of whom were depressed men who were abusing substances and undergoing separation. Additional categories included Intimate Ailing, Filial-Revenge, Familial-Psychotic, and Friend-Psychotic. Further, implications from this psychological autopsy study regarding risk assessment include use of collateral interviews regarding threats and past violence. PMID- 26259151 TI - Oestrogen sulfotransferase ablation sensitizes mice to sepsis. AB - Sepsis is the host's deleterious systemic inflammatory response to microbial infections. Here we report an essential role for the oestrogen sulfotransferase (EST or SULT1E1), a conjugating enzyme that sulfonates and deactivates estrogens, in sepsis response. Both the caecal ligation and puncture (CLP) and lipopolysaccharide models of sepsis induce the expression of EST and compromise the activity of oestrogen, an anti-inflammatory hormone. Surprisingly, EST ablation sensitizes mice to sepsis-induced death. Mechanistically, EST ablation attenuates sepsis-induced inflammatory responses due to compromised oestrogen deactivation, leading to increased sepsis lethality. In contrast, transgenic overexpression of EST promotes oestrogen deactivation and sensitizes mice to CLP induced inflammatory response. The induction of EST by sepsis is NF-kappaB dependent and EST is a NF-kappaB-target gene. The reciprocal regulation of inflammation and EST may represent a yet-to-be-explored mechanism of endocrine regulation of inflammation, which has an impact on the clinical outcome of sepsis. PMID- 26259153 TI - Attempted Serial Neonaticides: Case Report and a Brief Review of the Literature. AB - Neonaticide is an infant murder occurring on the day of birth. The case reports found in the literature are often focused on the mother as the agent in the context of pregnancy denial, dissociative symptoms, or psychosis. However, this report describes a rare case of attempted serial neonaticides, in which the acts were committed by a nurse at the nursery of a referral hospital in Brazil. The authors describe a forensic psychiatric evaluation for criminal responsibility and correlate the information from this particular case with relevant forensic themes, namely neonaticide, Munchausen by proxy syndrome, and serial healthcare killers. PMID- 26259155 TI - Role of Risk-Based Approach in the Prevention of Vertical Transmission of Neonatal Sepsis. AB - AIMS AND OBJECTIVES: Vertical transmission of infections remains a common cause of neonatal morbidity and mortality worldwide. We studied the risk-based approach in preventing the vertical transmission of neonatal sepsis. PATIENTS AND METHODS: A prospective case control study of 154 pregnant women with risk factors for vertical transmission of infections (subjects) and 154 pregnant women without the risk factors (control) at University of Ilorin Teaching Hospital, Ilorin from 1st July to 31st December, 2010. After counseling and consent taking, all participants had active management of labour and all subjects had parenteral intrapartum antibiotic prophylaxis with Ampicillin. There was postnatal evaluation of all babies for signs of neonatal sepsis followed by blood culture and treatment of culture positive babies. The outcome measures were signs and symptoms of neonatal sepsis, neonatal positive blood culture and maternal postpartum morbidity. RESULTS: Neonatal sepsis occurred in 16 babies (subjects=11, control=5); three babies had Early Onset Group B Streptococcal Disease (EOGBSD) (subjects=2, control=1; P=0.501) while 13 had non Group B Streptococcal (GBS) infections (subjects=9, control=4; P=0.113); onset of signs and symptoms was < 24hrs in all cases, incidence of EOGBSD were 12.9/1000 (subjects) and 6.5/1000 (controls). Subjects whose babies had sepsis had multiple risk factors; one dose of antibiotics and antibiotics to delivery interval < 2hours. There was no sepsis in babies of mothers who had adequate antibiotic prophylaxis. There was no maternal or neonatal death but 17.5% of subjects had maternal postpartum morbidities. CONCLUSION: The risk-based approach is a practicable alternative in preventing vertical transmission of neonatal sepsis if antibiotic prophylaxis is adequate before delivery. PMID- 26259156 TI - A Four-Year Retrospective Review of Very Low Birth Weight Babies Seen at the University of Abuja Teaching Hospital, Abuja, Nigeria. AB - AIMS AND OBJECTIVES: To review the outcome of very low birthweight infants admitted into the Special Care Baby Unit (SCBU) of University of Abuja Teaching Hospital (UATH), Gwagwalada, Abuja, Nigeria. METHODS: A retrospective review of medical records of very low birthweight (VLBW) babies seen at the SCBU of UATH over a 4-year period from April 2006 to March 2010, was undertaken. Data were obtained from patients' folders and analyzed. RESULTS: Overall survival was 60.8%. Survival of infants with birth weight below 1000 grams was 26.8% compared to 66.4% for those between 1000 and 1499 grams. The main determinants of survival were birth weight (p< 0.0001) and gestational age (p = 0.0106). Other predictors of outcome were development of features of respiratory distress syndrome within hours of delivery, recurrent apnoea, drainage of liquor of more than 18 hours before delivery, hyperkalaemia, lack of antenatal care and being born-before arrival (outborn). CONCLUSIONS: Survival rate is low compared to values from other communities in developing countries but better than values from many centres in Nigeria. Timely and effective management of apnoea, respiratory distress syndrome and prevention of extremely low birthweight (ELBW) deliveries through adequate antenatal care are required to improve on the current survival rate. PMID- 26259154 TI - Derivation and Validation of a Scoring System to Stratify Risk for Advanced Colorectal Neoplasia in Asymptomatic Adults: A Cross-sectional Study. AB - BACKGROUND: Several methods are recommended equally strongly for colorectal cancer screening in average-risk persons. Risk stratification would enable tailoring of screening within this group, with less invasive tests (sigmoidoscopy or occult blood tests) for lower-risk persons and colonoscopy for higher-risk persons. OBJECTIVE: To create a risk index for advanced neoplasia (colorectal cancer and adenomas or serrated polyps >=1.0 cm, villous histology, or high-grade dysplasia) anywhere in the colorectum, using the most common risk factors for colorectal neoplasia. DESIGN: Cross-sectional study. SETTING: Multiple endoscopy units, primarily in the Midwest. PATIENTS: Persons aged 50 to 80 years undergoing initial screening colonoscopy (December 2004 to September 2011). MEASUREMENTS: Derivation and validation of a risk index based on points from regression coefficients for age, sex, waist circumference, cigarette smoking, and family history of colorectal cancer. RESULTS: Among 2993 persons in the derivation set, prevalence of advanced neoplasia was 9.4%. Risks for advanced neoplasia in persons at very low, low, intermediate, and high risk were 1.92% (95% CI, 0.63% to 4.43%), 4.88% (CI, 3.79% to 6.18%), 9.93% (CI, 8.09% to 12.0%), and 24.9% (CI, 21.1% to 29.1%), respectively (P < 0.001). Sigmoidoscopy to the descending colon in the low-risk groups would have detected 51 of 70 (73% [CI, 61% to 83%]) advanced neoplasms. Among 1467 persons in the validation set, corresponding risks for advanced neoplasia were 1.65% (CI, 0.20% to 5.84%), 3.31% (CI, 2.08% to 4.97%), 10.9% (CI, 8.26% to 14.1%), and 22.3% (CI, 16.9% to 28.5%), respectively (P < 0.001). Sigmoidoscopy would have detected 21 of 24 (87.5% [CI, 68% to 97%]) advanced neoplasms. LIMITATIONS: Split-sample validation; results apply to first time screening. CONCLUSION: This index stratifies risk for advanced neoplasia among average-risk persons by identifying lower-risk groups for which noncolonoscopy strategies may be effective and efficient and a higher-risk group for which colonoscopy may be preferred. PRIMARY FUNDING SOURCE: National Cancer Institute, Walther Cancer Institute, Indiana University Simon Cancer Center, and Indiana Clinical and Translational Sciences Institute. PMID- 26259157 TI - Computed Tomography in the Evaluation of Recurrent Unprovoked Seizure Disorders at the University of Port Harcourt Teaching Hospital (UPTH), Nigeria. AB - AIMS AND OBJECTIVES: To evaluate the efficacy of cranial Computed Tomography (CT) Scan in detecting intracranial structural diseases related to recurrent unprovoked seizure disorder. PATIENTS AND METHODS: This was a retrospective analysis of the findings in 120 patients who had cranial CT scan for recurrent unprovoked seizure disorders in the Department of Radiology of University of Port Harcourt Teaching Hospital from August 2010 to September 2012. RESULTS: Of the 1,240 cranial CT scans performed during the period under review, only 120 (9.7%) cases had recurrent unprovoked seizure as indication for the procedure and were therefore included in the study. The patients were 71 (59.2%) males and 49 (40.8%) females. The ages of patients ranged from 1 month to 90 years. The mean age was 29.7+21.8 years. The highest prevalence of seizure disorder (25.8%) occurred in the less than ten year age group. The commonest lesions found were cerebral tumours 11 (9.2%), cerebral infarction 11 (9.2%) and cerebral atrophy 7 (5.8%). Cranial CT Scans were normal in 76 (63.3%) patients with recurrent unprovoked seizure disorders. The most frequent seizure type was generalized tonic clonic (76.7%). CONCLUSION: The use of Cranial CT Scan as a diagnostic tool led to the detection of intracranial lesions in 36.7% of patients with recurrent unprovoked seizure disorders. The detection of intracranial lesions in these patients would facilitate early and appropriate intervention. PMID- 26259158 TI - Risk Factors for Apical Periodontitis Sub-Urban Adult Population. AB - AIMS AND OBJECTIVES: To assess the risk factors of apical periodontitis (AP) in a Nigerian sub-urban adult population and to compare the findings with those previously reported for various population groups. MATERIALS AND METHODS: The study was based on a full mouth radiographic survey of 285 patients. Patients' age ranged from 18-60 years. All teeth were assessed individually and data recorded for caries, fractured / cracked teeth, root fillings, and tooth restorations. The gender, smoking habit, and frequency of dental visit were also recorded. Multiple logistic regression analyses were performed to identify predictors of AP in the individual. RESULTS: The prevalence of AP was 74.4%. The average number of teeth with AP per patient was 2.8 (range 1-5). AP was found to be more prevalent among people 40- 49 years old (87.2%). Primary carious lesions, fractured / cracked teeth, root fillings and coronal fillings were associated with the incidence of AP in the individual. Fractured teeth had a higher risk of developing AP than carious teeth. The presence of root fillings and coronal restorations were also associated with the development of AP. Smoking (OR=3.82; CI=2.17-6.75) and irregular dental visit (OR=6.73; CI=3.75-12.06) were statistically significant risk factors for developing AP. Gender was not a risk factor for AP (OR=0.86; CI=0.50-1.46). CONCLUSION: The prevalence of AP among adult Nigerians is slightly higher than reported figures for many Western societies. Fractured/cracked teeth had a higher risk of developing AP than carious teeth; hence patients with fractured / cracked teeth should seek treatment early to prevent the development of AP. PMID- 26259159 TI - Smokers and Non Smokers: A Comparison of Oral Health Practices and Effect of Non Surgical Periodontal Therapy on their Periodontium. AB - AIMS AND OBJECTIVES: To assess the oral hygiene measures and self report oral symptoms of smokers and non smokers, as well as evaluate and compare the effect of non-surgical periodontal therapy on their periodontium. MATERIALS AND METHODS: This was a quasi experimental study conducted on smokers and non smokers. Adult patient smokers were recruited into the study group and matched with age and sex controls (non-smokers). Data was collected on oral hygiene measures and self reported oral symptoms. The patients were examined and evaluated using oral indices. Each patient had scaling and root planing done and was re-examined after six weeks. Data was analysed using SPSS. RESULTS: Seventy-two patients completed the study with age ranging from 20 to 65 years and a mean age of 43.7 (+/- 17.8) years. Twenty-one percent (21%) of smokers and 42% of the non smokers reported experiencing gum bleeding, p = 0.041. Sixty percent of the smokers reported stains on their teeth compared to 29.7% of non smokers, p = 0.028. The baseline gingival and calculus indices were lower in smokers compared to non smokers while the plaque index was higher among the smokers. The response to scaling and root planing was worse among smokers comparing their gingival and calculus indices but better in terms of the plaque indices, however, these were not statistically significant. CONCLUSION: There were no significant differences between the response of smokers and non smokers to non surgical periodontal therapy although smokers experienced gingival bleeding less often and have lower gingival index. PMID- 26259160 TI - Hypertension and Diabetes Self-care Activities: A Hospital Based Pilot Survey in Benin City, Nigeria. AB - AIMS AND OBJECTIVES: The burden of hypertension and diabetes is on the increase globally with its attendant complications. Although self-care activities are critical to the successful management of both conditions, there are only a few reports on such activities, especially in this part of the world. This pilot study was therefore undertaken to assess the self-care activities among hypertensive and diabetic patients in Benin City. PATIENTS AND METHODS: Hypertensive and diabetic patients were consecutively recruited from the out- patient department of the University of Benin Teaching Hospital. The questionnaires were developed based on past assessment scales such as the Hypertension Self-Care Activity Level Effects (H-SCALE) and the Summary of Diabetes Self-Care Assessment (SDSCA) for hypertensive and diabetic participants respectively. RESULTS: A total of 85(32 hypertensive, 24 diabetic and 29 co morbid hypertensive diabetic) participants completed the study. Only 14 (16.5%) subjects had good self-care practice, 39 (45.9%) had fair practice while poor self-care practice was found in 32 (37.6%) subjects. Adherence to medications, clinic adherence, use of self-monitoring devices, regular exercising and dietician contact were generally low. However, only a relatively few subjects smoked tobacco or took significant alcohol. CONCLUSION: The health-related self care practice among the patients was generally not good. There was no significant difference in the overall level of self-care among hypertensive, diabetic patients or those with co-morbid conditions. There is need for more aggressive health education aimed at improving the current health-related self-care habits among these patients. PMID- 26259161 TI - IVF Pregnancy and Delivery following Ultrasound Scan Guided Aspiration of a Left Hydrosalpinx- A Case Report. AB - The presence of hydrosalpinges is known to significantly reduce the pregnancy and implantation rates following in vitro fertilization (IVF). Salpingectomy or laparoscopic tubal occlusion before IVF have been shown to significantly improve pregnancy rates. Aspiration of the hydrosalpinges at the time of oocyte retrieval for IVF had been proposed as a viable alternative. We present a 36- year old nullipara with unilateral hydrosalpinx who declined salpingectomy prior to IVF treatment and subsequently had two failed IVF cycles. She however became pregnant with the third IVF attempt, following transvaginal ultrasound scan guided aspiration of the hydrosalpinx fluid at the time of oocyte retrieval. Large randomized trials are needed to clearly identify the place of ultrasound scan guided aspiration of hydrosalpinges on IVF outcome. PMID- 26259162 TI - Mandibular Premolars with Multiple Roots:A Case Report. AB - Although the human mandibular premolars are known to exhibit variations in their root and canal configurations, multiple roots in mandibular premolars are rare though some cases have been reported. Prevalence of two rooted mandibular first and second premolars have been reported to be 1.8% - 2.1% and 0.4% respectively. Variations in root anatomy have been seen to differ with racial groups, gender and genetics. This case documents anatomical variation of mandibular premolars roots with a view to enhance successful endodontic treatments in Nigerians. A radiological investigation of the right and left mandibular jaw of a 20 year old man revealed that the mandibular right first and second premolars had two roots each. The left second premolar also presented with two roots. The occurrence of anatomical variations in the roots and canals of the human mandibular premolars cannot be overemphasised and should be considered diligently before performing endodontic treatment. PMID- 26259163 TI - Enantioselective sorption of the chiral fungicide metalaxyl on soil from non racemic aqueous solutions: Environmental implications. AB - Mechanisms governing the enantioselectivity of the processes that determine the behavior of chiral pollutants in the environment need to be better understood. Understanding these mechanisms should help improve predictions of the hazards and risks chiral compounds can pose to people and the environment. We report the results of batch sorption experiments indicating that the sorption of the chiral fungicide metalaxyl on soil from non-racemic initial solutions was enantioselective. While from a racemic initial solution the two enantiomers of metalaxyl were sorbed on the soil to the same extent, increasing the fraction of R-enantiomer in the initial solution led to enhanced sorption of this enantiomer and to reduced sorption of the S-enantiomer. Considering the shape of the sorption isotherms (S-type) and the sorption behavior of model sorbents, we attributed this effect to molecular interactions between metalaxyl enantiomer species at the sorbed state, where R-R metalaxyl interactions appeared to be more favorable than R-S metalaxyl interactions. We discuss important environmental implications of the proposed mechanism, such as those related to the fact that the biological degradation of metalaxyl is known to be an enantioselective process that can yield non-racemic residues in soils shortly after application of the fungicide as a racemic mixture. PMID- 26259164 TI - Intrinsic catalytic properties of extruded clay honeycomb monolith toward complete oxidation of air pollutants. AB - The present work highlights the intrinsic catalytic properties of extruded clay honeycomb monolith toward complete oxidation of various air pollutants namely CO, methane, propane, acetylene, propene, n-butene, methanol, ethanol, n-propanol, n butanol, acetone, dimethyl ether, benzene, toluene, o-xylene, monochlorobenzene and 1,2-dichlorobenzene. Total catalytic conversion was achieved for all tested compounds with different behaviors depending on pollutants' structural and chemical nature. The comparison of T50 values obtained from light-off curves allowed the establishment of the following reactivity sequence: ketone>alcohol>ether>CO>alkyne>aromatic>alkene>chlorinated aromatic>alkane. The intrinsic catalytic performances of the natural clay was ascribed to the implication of a quite complex mixture constituted by OH groups (Bronsted acids) and coordinately-unsaturated cations, such as Al(3+), Fe(3+) and Fe(2+) (Lewis acids). Hence, the combination of the clay's intrinsic catalytic performances and easier extrudability suggests a promissory potential for application in air pollution control. PMID- 26259165 TI - Efficient visible-light photocatalytic oxidation of gaseous NO with graphitic carbon nitride (g-C3N4) activated by the alkaline hydrothermal treatment and mechanism analysis. AB - In this paper, an enhanced visible-light photocatalytic oxidation (PCO) of NO (~ 400 ppm) in the presence of the graphitic carbon nitride (g-C3N4) treated by the alkaline hydrothermal treatment is evaluated. Various g-C3N4 samples were treated in different concentrations of NaOH solutions and the sample treated in 0.12 mol L(-1) of NaOH solution possesses the largest BET specific surface area as well as the optimal ability of the PCO of NO. UV-vis diffuse reflection spectra (DRS) and photoluminescence (PL) spectra were also conducted, and the highly improved photocatalytic performance is ascribed to the large specific surface area and high pore volume, which provides more adsorption and active sites, the wide visible-light adsorption edge and the narrow band gap, which is favorable for visible-light activation, as well as the decreased recombination rate of photo generated electrons and holes, which could contribute to the production of active species. Fluorescence spectra and a trapping experiment were conducted to further the mechanism analysis of the PCO of NO, illustrating that superoxide radicals (O2(-)) play the dominant role among active species in the PCO of NO. PMID- 26259166 TI - Motion Analysis-Based Skills Training and Assessment in Pediatric Laparoscopy: Construct, Concurrent, and Content Validity for the eoSim Simulator. AB - PURPOSE: To validate the eoSim((r)) (eoSurgical Ltd., Edinburgh, Scotland, United Kingdom) simulator for pediatric laparoscopy. MATERIALS AND METHODS: Participants were stratified according to their pediatric laparoscopy expertise. Three tasks were tested on the Pediatric Laparoscopic Surgery (PLS) and adapted eoSim simulators. Skill assessment was undertaken using motion analysis software for eoSim tasks and an existing validated scoring system for PLS tasks. Content validity was determined using Likert scale graded feedback responses. Construct validity was evaluated by investigating the respective abilities of the eoSim and PLS assessment tools to differentiate levels of experience. Concurrent validity was investigated by assessing the relationship between PLS and eoSim task completion times. RESULTS: In total, 28 participants (8 experts, 7 intermediates, and 13 novices) were recruited. Content validity results were comparable or more favorable for the eoSim. Construct validity for motion analysis parameters was established for instrument path length (objects transfer, P = .025; suturing, P = .012), speed (suturing, P = .034), acceleration (suturing, P = .048), and smoothness (suturing, P < .001). For all tasks, there were significant differences between level of experience groups for eoSim task completion times and PLS scores (P = .038 to < .001). Significant relationships were found between eoSim and PLS task completion times for the precision cutting and suturing tasks (rho = 0.298 and rho = 0.435, respectively). CONCLUSIONS: This study demonstrates validity of the adapted eoSim simulator for training in pediatric laparoscopy. Future work should focus on implementing and evaluating the proficiency-based training curriculum that is proposed using construct validity-derived metrics. PMID- 26259167 TI - Flexible Nitrogen Doped SiC Nanoarray for Ultrafast Capacitive Energy Storage. AB - The current trend with integrated energy-storage units in portable electronics lies in continuous advancements in nanostructured materials, thin-film manufacture technologies, and device architectures with enhanced functionality and reliability of existing components. Despite this, it is still challenging to provide cost-efficient solution to further improve the energy and power densities and cyclability of supercapacitors (SCs), especially at ultrafast rates while maintaining their environmentally friendly and even well-run at arbitrary harsh environments character. In this contribution, we report the fabrication of quasi aligned single crystalline 3C-SiC nanowire (3C-SiCNW) array with tailored shapes and nitrogen-doping (N-doping). The resultant large-scale SiCNWs were directly grown on the surface of a flexible carbon fabric via a simple chemical vapor deposition method. We found that the SC performance of SiCNW arrays can be substantially enhanced by nitrogen doping, which could favor a more localized impurity state near the conduction band edge that greatly improves the quantum capacitance and hence increases the bulk capacitance and the high-power capability. The measured areal capacitances are higher with values of 4.8 and 4.7 mF cm(-2), in aqueous and gel electrolytes, respectively. The all-solid-state flexible textile-based SCs (TSCs) made with these electrodes are mechanically robust under bent and twisted states. Further, they show a power density of 72.3 mW cm(-2) that is higher than that of electrolytic capacitors, and an energy density of 1.2 * 10(-4) mW.h cm(-2), in association with superior rate ability, cyclability, and being environmentally friendly. Such SiCNW-TSC devices allow for operations at ultrahigh rate up to 30 V s(-1), 2 orders of magnitude higher than that of conventional supercapacitors. All these data are comparable to the reported results for 1D nanostructure-based carbon nanotubes (CNTs) or graphenes, thus showing the promising application as large-area flexible textile electronics. PMID- 26259168 TI - Starch Biocatalyst Based on alpha-Amylase-Mg/Al-Layered Double Hydroxide Nanohybrids. AB - The design of new biocatalysts through the immobilization of enzymes, improving their stability and reuse, plays a major role in the development of sustainable methodologies toward the so-called green chemistry. In this work, alpha-amylase (AAM) biocatalyst based on Mg3Al-layered double-hydroxide (LDH) matrix was successfully developed with the adsorption method. The adsorption process was studied and optimized as a function of time and enzyme concentration. The biocatalyst was characterized, and the mechanism of interaction between AAM and LDH, as well as the immobilization effects on the catalytic activity, was elucidated. The adsorption process was fast and irreversible, thus yielding a stable biohybrid material. The immobilized AAM partially retained its enzymatic activity, and the biocatalyst rapidly hydrolyzed starch in an aqueous solution with enhanced efficiency at intermediate loading values of ca. 50 mg/g of AAM/LDH. Multiple attachments through electrostatic interactions affected the conformation of the immobilized enzyme on the LDH surface. The biocatalyst was successfully stored in its dry form, retaining 100% of its catalytic activity. The results reveal the potential usefulness of a LDH compound as a support of alpha-amylase for the hydrolysis of starch that may be applied in industrial and pharmaceutical processes as a simple, environmentally friendly, and low-cost biocatalyst. PMID- 26259169 TI - Cold tolerance in rice germinating seeds revealed by deep RNAseq analysis of contrasting indica genotypes. AB - Rice productivity is largely affected by low temperature, which can be harmful throughout plant development, from germination to grain filling. Germination of indica rice cultivars under cold is slow and not uniform, resulting in irregular emergence and small plant population. To identify and characterize novel genes involved in cold tolerance during the germination stage, two indica rice genotypes (sister lines previously identified as cold-tolerant and cold sensitive) were used in parallel transcriptomic analysis (RNAseq) under cold treatment (seeds germinating at 13 degrees C for 7 days). We detected 1,361 differentially expressed transcripts. Differences in gene expression found by RNAseq were confirmed for 11 selected genes using RT-qPCR. Biological processes enhanced in the cold-tolerant seedlings include: cell division and expansion (confirmed by anatomical sections of germinating seeds), cell wall integrity and extensibility, water uptake and membrane transport capacity, sucrose synthesis, generation of simple sugars, unsaturation of membrane fatty acids, wax biosynthesis, antioxidant capacity (confirmed by histochemical staining of H2O2), and hormone and Ca(2+)-signaling. The cold-sensitive seedlings respond to low temperature stress increasing synthesis of HSPs and dehydrins, along with enhanced ubiquitin/proteasome protein degradation pathway and polyamine biosynthesis. Our findings can be useful in future biotechnological approaches aiming to cold tolerance in indica rice. PMID- 26259170 TI - Ups and downs in alfalfa: Proteomic and metabolic changes occurring in the growing stem. AB - The expanding interest for using lignocellulosic biomass in industry spurred the study of the mechanisms underlying plant cell-wall synthesis. Efforts using genetic approaches allowed the disentanglement of major steps governing stem fibre synthesis. Nonetheless, little is known about the relations between the stem maturation and the evolution of its proteome. During Medicago sativa L. maturation, the different internodes grow asynchronously allowing the discrimination of various developmental stages on a same stem. In this study, the proteome of three selected regions of the stem of alfalfa (apical, intermediate and basal) was analyzed and combined with a compositional analysis of the different stem parts. Interestingly, the apical and the median regions share many similarities: high abundance of chloroplast- and mitochondrial-related proteins together with the accumulation of proteins acting in the early steps of fibre production. In the mature basal region, forisomes and stress-related proteins accumulate. The RT-qPCR assessment of the expression of genes coding for members of the cellulose synthase family likewise indicates that fibres and the machinery responsible for the deposition of secondary cell walls are predominantly formed in the apical section. Altogether, this study reflects the metabolic change from the fibre production in the upper stem regions to the acquisition of defence related functions in the fibrous basal part. PMID- 26259171 TI - Improving potato drought tolerance through the induction of long-term water stress memory. AB - Knowledge of drought tolerance in potato is limited and very little is known about stress memory in this crop. In the present study, long-term stress memory was tested on tuber yield and drought tolerance related traits in three potato varieties (Unica, Desiree and Sarnav) with contrasted yields under water restriction. Seed tubers produced by plants grown under non-restricted (non primed tubers) and restricted (primed tubers) water conditions were sown and exposed to similar watering treatments. Tuber yield and leaf greenness of plants from primed and non-primed seeds as well as tuber carbon isotope discrimination (Delta(13)C) and antioxidant activity (AA) responses to watering treatments were compared. Higher tuber yield, both under non-restricted and restricted water regimes, was produced by primed Sarnav plants. The decrease of tuber yield and Delta(13)C with water restriction was lower in primed Unica plants. Long-term stress memory consequently appears to be highly genotype-dependent in potato. Its expression in plants originated from primed tubers and facing water restriction seems to be positively associated to the degree of inherent capability of the cultivar to yield under water restriction. However, other effects of priming appear to be genotype-independent as priming enhanced the tuber AA in response to water restriction in the three varieties. PMID- 26259172 TI - Transcriptome analysis reveals that distinct metabolic pathways operate in salt tolerant and salt-sensitive upland cotton varieties subjected to salinity stress. AB - Salinity stress is one of the most devastating abiotic stresses in crop plants. As a moderately salt-tolerant crop, upland cotton (Gossypium hirsutum L.) is a major cash crop in saline areas and a suitable model for salt stress tolerance research. In this study, we compared the transcriptome changes between the salt tolerant upland cotton cultivar Zhong 07 and salt-sensitive cultivar Zhong G5 in response to NaCl treatments. Transcriptional regulation, signal transduction and secondary metabolism in two varieties showed significant differences, all of which might be related to mechanisms underlying salt stress tolerance. The transcriptional profiles presented here provide a foundation for deciphering the mechanism underlying salt tolerance. Based on our findings, we proposed several candidate genes that might be used to improve salt tolerance in upland cotton. PMID- 26259173 TI - miRNAs and lncRNAs in reproductive development. AB - Non-coding RNAs (ncRNAs) regulate gene expression at the transcriptional and post transcriptional levels. Many ncRNAs have been identified in the past decade, including small ncRNAs, such as microRNAs (miRNAs), and long ncRNAs (lncRNAs). These novel molecules have important roles in a wide range of biological processes such as the regulation of reproduction and sex determination. Due to their ability to regulate specific genes or entire gene families, these molecules have the potential for uses in the development of breeding strategies as well as in the genetic modification of agronomic traits. In this review, we summarize recent progress on the understanding of plant miRNAs and lncRNAs in male and female development. We also discuss future challenges of using these molecules in agricultural applications, including transgenic plants in hybrid breeding, for novel genetic trait selection, for rapid character screening, and genetic modification for crop improvement. PMID- 26259174 TI - Instability of the Arabidopsis mutant csn5a-2 caused by epigenetic modification of intronic T-DNA. AB - T-DNA insertion mutants play a crucial role in elucidating Arabidopsis gene function. In some cases, two or more T-DNA mutants are combined to study genetic interactions between homologous genes or genes hypothesized to act in the same pathway. We studied the significance of protein-protein interactions between CSN5A and ROP11 by crossing three independent rop11 T-DNA insertion mutants with csn5a-2, a partial loss-of-function intronic T-DNA insertion mutant. The csn5a-2 single mutant is severely stunted, but double rop11 csn5a-2mutants were rescued and exhibited increased CSN5A transcript and protein levels. The rescued phenotype was maintained in non-Mendelian fashion when the csn5a-2 single mutant was re-isolated from the rop11-1 csn5a-2 double mutant, and was sensitive to two inhibitors of DNA methylation. Loss of kanamycin resistance was also observed in re-isolated csn5a-2. These findings indicate that the rescue of csn5a-2 resulted from a trans T-DNA-mediated epigenetic effect on the csn5a-2 intronic T-DNA, similar to recent reports involving the intronic T-DNA mutants ag-TD, ben1-1, and cob-6. Thus the work reported here provides further support for the recommendation that mutants created through novel combinations of T-DNA alleles should be carefully evaluated for evidence of epigenetic modification of T-DNA before final conclusions are drawn. PMID- 26259175 TI - Phytochrome-interacting factors PIF4 and PIF5 negatively regulate anthocyanin biosynthesis under red light in Arabidopsis seedlings. AB - Light is an important environmental factor inducing anthocyanin accumulation in plants. Phytochrome-interacting factors (PIFs) have been shown to be a family of bHLH transcription factors involved in light signaling in Arabidopsis. Red light effectively increased anthocyanin accumulation in wild-type Col-0, whereas the effects were enhanced in pif4 and pif5 mutants but impaired in overexpression lines PIF4OX and PIF5OX, indicating that PIF4 and PIF5 are both negative regulators for red light-induced anthocyanin accumulation. Consistently, transcript levels of several genes involved in anthocyanin biosynthesis and regulatory pathway, including CHS, F3'H, DFR, LDOX, PAP1 and TT8, were significantly enhanced in mutants pif4 and pif5 but decreased in PIF4OX and PIF5OX compared to in Col-0, indicating that PIF4 and PIF5 are transcriptional repressor of these gene. Transient expression assays revealed that PIF4 and PIF5 could repress red light-induced promoter activities of F3'H and DFR in Arabidopsis protoplasts. Furthermore, chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) test and electrophoretic mobility shift assay (EMSA) showed that PIF5 could directly bind to G-box motifs present in the promoter of DFR. Taken together, these results suggest that PIF4 and PIF5 negatively regulate red light induced anthocyanin accumulation through transcriptional repression of the anthocyanin biosynthetic genes in Arabidopsis. PMID- 26259176 TI - Inheritance and molecular mapping of Rf6 locus with pollen fertility restoration ability on A1 and A2 cytoplasms in sorghum. AB - Of the several male sterility cytoplasms available as an alternative to the widely exploited A1 (milo) cytoplasm in sorghum, A2 is more suitable for commercial exploitation. Diversification of genetic and cytoplasmic base of hybrids involving A2 cytoplasm necessitates mapping of fertility restorer (Rf) genes for use in marker-assisted restorer development. We mapped a major male fertility restoration locus on sorghum chromosome 4 tightly linked with SSR markers, SB2387 and SB2388. This new fertility locus, Rf6, was able to restore male fertility on both A1 and A2 cytoplasms. Analysis of the genomic region around the Rf6 locus identified six genes including a pentatricopeptide repeat (PPR) gene, Sobic.004G004100. With its similar restoration ability to Rf1, Rf2 and Rf5 loci in sorghum, it is most likely that the Rf6 is a member of the PPR gene family, and the PPR gene Sobic.004G004100 could be a candidate for fertility restoration on A1 and A2 cytoplasms. PMID- 26259177 TI - Dissecting the role of two cytokinin analogues (INCYDE and PI-55) on in vitro organogenesis, phytohormone accumulation, phytochemical content and antioxidant activity. AB - There is a continuous search for new chemical entities to expand the collection of suitable compounds to increase the efficiency of micropropagation protocols. Two cytokinin (CK) analogues, 2-chloro-6-(3-methoxyphenyl)aminopurine (INCYDE) and CK antagonist 6-(2-hydroxy-3-methylbenzylamino)purine (PI-55) were used as a tool to elucidate the auxin-CK crosstalk under in vitro conditions in the medicinally important plant, Eucomis autumnalis subspecies autumnalis. These compounds were tested at 0.01, 0.1 and 10 MUM alone as well as in combination with benzyladenine (BA) and naphthaleneacetic acid (NAA). The organogenesis, phytohormone content, phytochemical and antioxidant response in 10 week-old-in vitro regenerated E. autumnalis subspecies autumnalis was evaluated. INCYDE generally favoured shoot regeneration while the effect of PI-55 was more evident in root proliferation. Overall, INCYDE promoted the accumulation of higher concentrations and varieties of endogenous CK relative to the PI-55 treatments. In contrast, higher concentration of indole-3-acetic acid and 2-oxindole-3-acetic acid were generally observed in PI-55-supplemented cultures when compared to plantlets derived from INCYDE. Both CK analogues (individually and in-conjunction with exogenously applied PGRs) significantly influenced the phytochemicals and consequently the antioxidant potential of the in vitro regenerants. These results provided insight on how to alleviate root inhibition, a problem which causes considerable loss of several elite species during micropropagation. PMID- 26259178 TI - The control of tomato fruit elongation orchestrated by sun, ovate and fs8.1 in a wild relative of tomato. AB - Within the cultivated tomato germplasm, sun, ovate and fs8.1 are the three predominant QTLs controlling fruit elongation. Although SUN and OVATE have been cloned, their role in plant growth and development are not well understood. To compare and contrast the effects of the three QTLs in a homogeneous background, we developed near isogenic lines (NILs) in the wild species Solanum pimpinellifolium LA1589 background. We carried out detailed morphological characterization of reproductive and vegetative organs in the single, double and triple NILs and determined the epistatic interactions of the three loci affecting fruit shape. The phenotypic evaluations demonstrated that the three loci regulate unique aspects of ovary and fruit elongation and in different temporal manners. The strongest effect on organ shape was caused by sun. In addition to fruit shape, sun also affected leaf and sepal elongation and stem thickness. The synergistic interaction between sun and ovate or fs8.1 suggested that the pathways involving SUN, OVATE and the gene(s) underlying fs8.1 may converge at a common node. The results of an extensive profiling analysis suggested that the degree of fruit elongation was not related to the accumulation of any of the classical hormones. PMID- 26259179 TI - Genome-wide analysis of phylogeny, expression profile and sub-cellular localization of SKP1-Like genes in wild tomato. AB - SKP1 is a core component of SCF complex, a major type of E3 ubiquitin ligase catalyzing the last step in ubiquitin-mediated protein degradation pathway. In present study, SKP1 gene family in Solanum pimpinellifolium (SSK), a wild species of tomato, was investigated. A total of 19 SSK genes were identified through homologous search. Their chromosomal locations, gene structures, phylogeny, expression profiles, sub-cellular localizations and protein-protein interaction patterns with putative F-box proteins were analyzed in detail. The high homology and similar expression patterns among clustered SSK genes in chromosome suggested that they may have evolved from duplication events and are functionally redundant. Sub-cellular localization indicated that most of the SSK proteins are distributed in both cytosol and nucleus, except for SSK8, which is detected in cytosol only. Tissue-specific expression patterns suggested that many SSK genes may be involved in tomato fruit development. Furthermore, several SSK genes were found to be responsive to heat stress and salicylic acid treatment. Based on phylogenetic analysis, expression profiles and protein interaction property, we proposed that tomato SSK1 and SSK2 might have similar function to ASK1 and ASK2 in Arabidopsis. PMID- 26259180 TI - Identification of nuclear target proteins for S-nitrosylation in pathogen-treated Arabidopsis thaliana cell cultures. AB - Nitric oxide (NO) is a significant signalling molecule involved in the regulation of many different physiological processes in plants. One of the most imperative regulatory modes of action of NO is protein S-nitrosylation--the covalent attachment of an NO group to the sulfur atom of cysteine residues. In this study, we focus on S-nitrosylation of Arabidopsis nuclear proteins after pathogen infection. After treatment of Arabidopsis suspension cell cultures with pathogens, nuclear proteins were extracted and treated with the S-nitrosylating agent S-nitrosoglutathione (GSNO). A biotin switch assay was performed and biotin labelled proteins were purified by neutravidin affinity chromatography and identified by mass spectrometry. A total of 135 proteins were identified, whereas nuclear localization has been described for 122 proteins of them. 117 of these proteins contain at least one cysteine residue. Most of the S-nitrosylated candidates were involved in protein and RNA metabolism, stress response, and cell organization and division. Interestingly, two plant-specific histone deacetylases were identified suggesting that nitric oxide regulated epigenetic processes in plants. In sum, this work provides a new collection of targets for protein S nitrosylation in Arabidopsis and gives insight into the regulatory function of NO in the nucleus during plant defense response. Moreover, our data extend the knowledge on the regulatory function of NO in events located in the nucleus. PMID- 26259181 TI - Mutation of FdC2 gene encoding a ferredoxin-like protein with C-terminal extension causes yellow-green leaf phenotype in rice. AB - Ferredoxins (Fds) are small iron-sulfur proteins that mediate electron transfer in a wide range of metabolic reactions. Besides Fds, there is a type of Fd-like proteins designated as FdC, which have conserved elements of Fds, but contain a significant C-terminal extension. So far, only two FdC genes of Arabidopsis (Arabidopsis thaliana) have been identified in higher plants and thus the functions of FdC proteins remain largely unknown. In this study, we isolated a yellow-green leaf mutant, 501ys, in rice (Oryza sativa). The mutant exhibited yellow-green leaf phenotype and reduced chlorophyll level. The phenotype of 501ys was caused by mutation of a gene on rice chromosome 3. Map-based cloning of this mutant resulted in identification of OsFdC2 gene (LOC_Os03g48040) showing high identity with Arabidopsis FdC2 gene (AT1G32550). OsFdC2 was expressed most abundantly in leaves and its encoded protein was targeted to the chloroplast. In 501ys mutant, a missense mutation was detected in DNA sequence of the gene, resulting in an amino acid change in the encoded protein. The mutant phenotype was rescued by introduction of the wild-type gene. Therefore, we successfully identified FdC2 gene via map-based cloning approach, and demonstrated that mutation of this gene caused yellow-green leaf phenotype in rice. PMID- 26259182 TI - Characterization of multiple SPS knockout mutants reveals redundant functions of the four Arabidopsis sucrose phosphate synthase isoforms in plant viability, and strongly indicates that enhanced respiration and accelerated starch turnover can alleviate the blockage of sucrose biosynthesis. AB - We characterized multiple knock-out mutants of the four Arabidopsis sucrose phosphate synthase (SPSA1, SPSA2, SPSB and SPSC) isoforms. Despite their reduced SPS activity, spsa1/spsa2, spsa1/spsb, spsa2/spsb, spsa2/spsc, spsb/spsc, spsa1/spsa2/spsb and spsa2/spsb/spsc mutants displayed wild type (WT) vegetative and reproductive morphology, and showed WT photosynthetic capacity and respiration. In contrast, growth of rosettes, flowers and siliques of the spsa1/spsc and spsa1/spsa2/spsc mutants was reduced compared with WT plants. Furthermore, these plants displayed a high dark respiration phenotype. spsa1/spsb/spsc and spsa1/spsa2/spsb/spsc seeds poorly germinated and produced aberrant and sterile plants. Leaves of all viable sps mutants, except spsa1/spsc and spsa1/spsa2/spsc, accumulated WT levels of nonstructural carbohydrates. spsa1/spsc leaves possessed high levels of metabolic intermediates and activities of enzymes of the glycolytic and tricarboxylic acid cycle pathways, and accumulated high levels of metabolic intermediates of the nocturnal starch-to sucrose conversion process, even under continuous light conditions. Results presented in this work show that SPS is essential for plant viability, reveal redundant functions of the four SPS isoforms in processes that are important for plant growth and nonstructural carbohydrate metabolism, and strongly indicate that accelerated starch turnover and enhanced respiration can alleviate the blockage of sucrose biosynthesis in spsa1/spsc leaves. PMID- 26259183 TI - Early events induced by the toxin deoxynivalenol lead to programmed cell death in Nicotiana tabacum cells. AB - Deoxynivalenol (DON) is a mycotoxin affecting animals and plants. This toxin synthesized by Fusarium culmorum and Fusarium graminearum is currently believed to play a decisive role in the fungal phytopathogenesis as a virulence factor. Using cultured cells of Nicotiana tabacum BY2, we showed that DON-induced programmed cell death (PCD) could require transcription and translation processes, in contrast to what was observed in animal cells. DON could induce different cross-linked pathways involving (i) reactive oxygen species (ROS) generation linked, at least partly, to a mitochondrial dysfunction and a transcriptional down-regulation of the alternative oxidase (Aox1) gene and (ii) regulation of ion channel activities participating in cell shrinkage, to achieve PCD. PMID- 26259184 TI - Occurrence, genetic control and evolution of non-target-site based resistance to herbicides inhibiting acetolactate synthase (ALS) in the dicot weed Papaver rhoeas. AB - Non-target-site resistance (NTSR) to herbicides is a major issue for the chemical control of weeds. Whilst predominant in grass weeds, NTSR remains largely uninvestigated in dicot weeds. We investigated the occurrence, inheritance and genetic control of NTSR to acetolactate synthase (ALS) inhibitors in Papaver rhoeas (corn poppy) using progenies from plants with potential NTSR to the imidazolinone herbicide imazamox. NTSR to imazamox was inherited from parents over two successive generations. NTSR to tritosulfuron (a sulfonylurea) was observed in F1 generations and inherited in F2 generations. NTSR to florasulam (a triazolopyrimidine) emerged in F2 generations. Our findings suggest NTSR was polygenic and gradually built-up by accumulation over generations of loci with moderate individual effects in single plants. We also demonstrated that ALS alleles conferring herbicide resistance can co-exist with NTSR loci in P. rhoeas plants. Previous research focussed on TSR in P. rhoeas, which most likely caused underestimation of NTSR significance in this species. This may also apply to other dicot species. From our data, resistance to ALS inhibitors in P. rhoeas appears complex, and involves well-known mutant ALS alleles and a set of unknown NTSR loci that confer resistance to ALS inhibitors from different chemical families. PMID- 26259185 TI - A decrease in phytic acid content substantially affects the distribution of mineral elements within rice seeds. AB - Phytic acid (myo-inositol hexakisphosphate; InsP6) is the storage compound of phosphorus and many mineral elements in seeds. To determine the role of InsP6 in the accumulation and distribution of mineral elements in seeds, we performed fine mappings of mineral elements through synchrotron-based X-ray microfluorescence analysis using developing seeds from two independent low phytic acid (lpa) mutants of rice (Oryza sativa L.). The reduced InsP6 in lpa seeds did not affect the translocation of mineral elements from vegetative organs into seeds, because the total amounts of phosphorus and the other mineral elements in lpa seeds were identical to those in the wild type (WT). However, the reduced InsP6 caused large changes in mineral localization within lpa seeds. Phosphorus and potassium in the aleurone layer of lpa greatly decreased and diffused into the endosperm. Zinc and copper, which were broadly distributed from the aleurone layer to the inner endosperm in the WT, were localized in the narrower space around the aleurone layer in lpa mutants. We also confirmed that similar distribution changes occurred in transgenic rice with the lpa phenotype. Using these results, we discussed the role of InsP6 in the dynamic accumulation and distribution patterns of mineral elements during seed development. PMID- 26259186 TI - Cellular and molecular aspects of quinoa leaf senescence. AB - During leaf senescence, degradation of chloroplasts precede to changes in nuclei and other cytoplasmic organelles, RuBisCO stability is progressively lost, grana lose their structure, plastidial DNA becomes distorted and degraded, the number of plastoglobuli increases and abundant senescence-associated vesicles containing electronically dense particles emerge from chloroplasts pouring their content into the central vacuole. This study examines quinoa leaf tissues during development and senescence using a range of well-established markers of programmed cell death (PCD), including: morphological changes in nuclei and chloroplasts, degradation of RuBisCO, changes in chlorophyll content, DNA degradation, variations in ploidy levels, and changes in nuclease profiles. TUNEL reaction and DNA electrophoresis demonstrated that DNA fragmentation in nuclei occurs at early senescence, which correlates with induction of specific nucleases. During senescence, metabolic activity is high and nuclei endoreduplicate, peaking at 4C. At this time, TEM images showed some healthy nuclei with condensed chromatin and nucleoli. We have found that DNA fragmentation, induction of senescence-associated nucleases and endoreduplication take place during leaf senescence. This provides a starting point for further research aiming to identify key genes involved in the senescence of quinoa leaves. PMID- 26259187 TI - Loss of function of OsMADS3 via the insertion of a novel retrotransposon leads to recessive male sterility in rice (Oryza sativa). AB - Natural mutation is the source of natural variation, which is the fundamental basis for the genetic improvement of crops. During the process of developing a recombinant inbred line (RI), a spontaneous mutagenesis in RI127 led to the production of the recessive male-sterile line RI127S. Via a map-based cloning approach, the gene controlling the male sterility was identified as OsMADS3, which was previously reported to be associated with floral organ development and male sterility. Thermal asymmetric interlaced PCR isolated one 1633-bp insertion in OsMADS3 in RI127S, which damaged its function due to failed transcription. The 1633-bp insertion was derived from a fragment flanked by retrotransposon genes on chromosome 5. Seven haplotypes of OsMADS3 were observed among 529 cultivars and 107 wild rice accessions, and 98% of the investigated genotypes carried the same H2 haplotype, indicating that OsMADS3 is highly conserved. RI127S has the combined genome constitution of its parents, indica rice Teqing and japonica 02428, and carries the widely compatible S5 gene donated by 02428. RI127 exhibits good performance in regard to its agronomic traits and has a wide compatibility. Therefore, RI127S would be an elite mediator for recurrent breeding in cases requiring a tedious hand-crossing-based inter-crossing phase. RI127S can be crossed not only with indica rice but also with japonica rice, thus providing breeders with flexible arrangements in recurrent breeding programs. PMID- 26259189 TI - Metalloido-porins: Essentiality of Nodulin 26-like intrinsic proteins in metalloid transport. AB - Metalloids are a group of physiologically important elements ranging from the essential to the highly toxic. Arsenic, antimony, germanium, and tellurium are highly toxic to plants themselves and to consumers of metalloid-contaminated plants. Boron, silicon, and selenium fulfill essential or beneficial functions in plants. However, when present at high concentrations, boron and selenium cause toxicity symptoms that are detrimental to plant fitness and yield. Consequently, all plants require efficient membrane transport systems to control the uptake and extrusion of metalloids into or out of the plant and their distribution within the plant body. Several Nodulin 26-like intrinsic proteins (NIPs) that belong to the aquaporin plant water channel protein family facilitate the diffusion of uncharged metalloid species. Genetic, physiological, and molecular evidence is that NIPs from primitive to higher plants not only transport all environmentally important metalloids, but that these proteins have a major role in the uptake, translocation, and extrusion of metalloids in plants. As most of the metalloid permeable NIP aquaporins are impermeable or are poorly permeable to water, these NIP channel proteins should be considered as physiologically essential metalloido porins. PMID- 26259188 TI - Functional characterization of FaNIP1;1 gene, a ripening-related and receptacle specific aquaporin in strawberry fruit. AB - Strawberry fruit (Fragaria * ananassa) is a soft fruit with high water content at ripe stage (more than 90% of its fresh weight). Aquaporins play an important role in plant water homeostasis, through the facilitation of water transport and solutes. We report the role played by FaNIP1;1 in the receptacle ripening process. The analysis by qRT-PCR of FaNIP1;1 showed that this gene is mainly expressed in fruit receptacle and has a ripening-related expression pattern that was accompanied by an increase in both the abscisic acid and water content of the receptacle throughout fruit ripening. Moreover, FaNIP1;1 was induced in situations of water deficit. Additionally, we show that FaNIP1;1 expression was positively regulated by abscisic acid and negatively regulated by auxins. The water transport capacity of FaNIP1;1 was determined by a stopped-flow spectroscopy in yeast over-expressing FaNIP1;1. Glycerol, H2O2 and boron transport were also demonstrated in yeast. On the other hand, GFP-FaNIP1;1 fusion protein was located in plasma membrane. In conclusion, FaNIP1;1 seems to play an important role increasing the plasma membrane permeability, that allows the water accumulation in the strawberry fruit receptacle throughout the ripening process. PMID- 26259190 TI - Calcineurin B-like 3 calcium sensor associates with and inhibits 5' methylthioadenosine nucleosidase 2 in Arabidopsis. AB - Calcineurin B-like (CBL) proteins constitute a unique family of calcium sensor relays in plants. It is well known that CBLs detect the calcium signals elicited by a variety of abiotic stresses and relay the information to a group of serine/threonine protein kinases called CBL-interacting protein kinases (CIPKs). In this study, we found that a few CBL members can also target another group of enzymes 5'-methylthioadenosine nucleosidases (MTANs), which are encoded by two genes in Arabidopsis, AtMTAN1 and AtMTAN2. In the yeast two-hybrid system, AtMTAN1 interacted with multiple CBL members such as CBL2, CBL3 and CBL6, whereas AtMTAN2 associated exclusively with CBL3. We further demonstrated that the CBL3 AtMTAN2 association occurs in a calcium-dependent manner, which results in a significant decrease in the enzyme activity of the AtMTAN2 protein. Taken together, these results clearly indicate that the CBL family can target at least two distinct groups of enzymes (CIPKs and MTANs), conferring an additional level of complexity on the CBL-mediated signaling networks. In addition, our finding also provides a novel molecular mechanism by which calcium signals are transduced to alter metabolite profiles in plants. PMID- 26259191 TI - The mechanism underlying fast germination of tomato cultivar LA2711. AB - Seed germination is important for early plant morphogenesis as well as abiotic stress tolerance, and is mainly controlled by the phytohormones abscisic acid (ABA) and gibberellic acid (GA). Our previous studies identified a salt-tolerant tomato cultivar, LA2711, which is also a fast-germinating genotype, compared to its salt-sensitive counterpart, ZS-5. In an effort to further clarify the mechanism underlying this phenomenon, we compared the dynamic levels of ABA and GA4, the transcript abundance of genes involved in their biosynthesis and catabolism as well as signal transduction between the two cultivars. In addition, we tested seed germination sensitivity to ABA and GAs. Our results revealed that insensitivity of seed germination to exogenous ABA and low ABA content in seeds are the physiological mechanisms conferring faster germination rates of LA2711 seeds. SlCYP707A2, which encodes an ABA catabolic enzyme, may play a decisive role in the fast germination rate of LA2711, as it showed a significantly higher level of expression in LA2711 than ZS-5 at most time points tested during germination. The current results will enable us to gain insight into the mechanism(s) regarding seed germination of tomato and the role of fast germination in stress tolerance. PMID- 26259192 TI - Competency for shoot regeneration from Arabidopsis root explants is regulated by DNA methylation. AB - Plants exhibit high capacity to regenerate in three alternative pathways: tissue repair, somatic embryogenesis and de novo organogenesis. For most plants, de novo organ initiation can be easily achieved in tissue culture by exposing explants to auxin and/or cytokinin, yet the competence to regenerate varies among species and within tissues from the same plant. In Arabidopsis, root explants incubated directly on cytokinin-rich shoot inducing medium (SIM-direct), are incapable of regenerating shoots, and a pre-incubation step on auxin-rich callus inducing medium (CIM) is required to acquire competency to regenerate on the SIM. However the mechanism underlying competency acquisition still remains elusive. Here we show that the chromomethylase 3 (cmt3) mutant which exhibits significant reduction in CHG methylation, shows high capacity to regenerate on SIM-direct and that regeneration occurs via direct organogenesis. In WT, WUSCHEL (WUS) promoter, an essential gene for shoot formation, is highly methylated, and its expression on SIM requires pre-incubation on CIM. However, in cmt3, WUS expression induced by SIM-direct. We propose that pre-incubation on CIM is required for the re activation of cell division. Following the transfer of roots to SIM, the intensive cell division activity continues, and in the presence of cytokinin leads to a dilution in DNA methylation that allows certain genes required for shoot regeneration to respond to SIM, thereby advancing shoot formation. PMID- 26259193 TI - Expression of peach sucrose transporters in heterologous systems points out their different physiological role. AB - Sucrose is the major phloem-translocated component in a number of economically important plant species. The comprehension of the mechanisms involved in sucrose transport in peach fruit appears particularly relevant, since the accumulation of this sugar, during ripening, is crucial for the growth and quality of the fruit. Here, we report the functional characterisation and subcellular localisation of three sucrose transporters (PpSUT1, PpSUT2, PpSUT4) in peach, and we formulate novel hypotheses about their role in accumulation of sugar. We provide evidence, about the capability of both PpSUT1 and PpSUT4, expressed in mutant yeast strains to transport sucrose. The functionality of PpSUT1 at the plasma membrane, and of PpSUT4 at the tonoplast, has been demonstrated. On the other hand, the functionality of PpSUT2 was not confirmed: this protein is unable to complement two sucrose uptake-deficient mutant yeast strains. Our results corroborate the hypotheses that PpSUT1 partakes in phloem loading in leaves, and PpSUT4 sustains cell metabolism by regulating sucrose efflux from the vacuole. PMID- 26259194 TI - miRNA778 and SUVH6 are involved in phosphate homeostasis in Arabidopsis. AB - microRNAs (miRNAs) play an important role in plant adaptation to phosphate (Pi) starvation. Histone methylation can remodel chromatin structure and mediate gene expression. This study identified Arabidopsis miR778, a Pi-responsive miRNA, and its target gene Su(var) 3-9 homologs 6 (SUVH6) encoding a histone H3 lysine 9 (H3K9) methyltransferase. Overexpression of miR778 moderately enhanced primary and lateral root growth, free phosphate accumulation in shoots, and accumulation of anthocyanin under Pi deficient conditions. miR778 overexpression relieved the arrest of columella cell development under Pi starvation. Conversely, transgenic plants overexpressing a miR778-target mimic (35S::MIM778), that act as a sponge and sequesters miR778, showed opposite phenotypes of 35S::miR778 plants under Pi deficiency. Expression of several Pi deficiency-responsive genes such as miR399, Phosphate Transporter (PHT1;4), Low Phosphate-Resistant1 (LPR1) and Production of Anthocyanin Pigment 1 (PAP1) were elevated in the miR778 overexpressing plants, suggesting that both miR778 and SUVH6 are involved in phosphate homeostasis in plants. This study has provided a basis for further investigation on how SUVH6 regulates its downstream genes through chromatin remodeling and DNA methylation in plants stressed by Pi deficiency. PMID- 26259195 TI - K(+) accumulation in the cytoplasm and nucleus of the salt gland cells of Limonium bicolor accompanies increased rates of salt secretion under NaCl treatment using NanoSIMS. AB - Recretohalophytes with specialized salt-secreting structures (salt glands) can secrete excess salts from plant, while discriminating between Na(+) and K(+). K(+)/Na(+) ratio plays an important role in plant salt tolerance, but the distribution and role of K(+) in the salt gland cells is poorly understood. In this article, the in situ subcellular localization of K and Na in the salt gland of the recretohalophyte Limonium bicolor Kuntze is described. Samples were prepared by high-pressure freezing (HPF), freeze substitution (FS) and analyzed using NanoSIMS. The salt gland of L. bicolor consists of sixteen cells. Higher signal strength of Na(+) was located in the apoplast of salt gland cells. Compared with control, 200 mM NaCl treatment led to higher signal strength of K(+) and Na(+) in both cytoplasm and nucleus of salt gland cells although K(+)/Na(+) ratio in both cytoplasm and nucleus were slightly reduced by NaCl. Moreover, the rate of Na(+) secretion per salt gland of L. bicolor treated with 200 mM NaCl was five times that of controls. These results suggest that K(+) accumulation both in the cytoplasm and nucleus of salt gland cells under salinity may play an important role in salt secretion, although the exact mechanism is unknown. PMID- 26259196 TI - Modelling the relationship between CO2 assimilation and leaf anatomical properties in tomato leaves. AB - The CO2 concentration near Rubisco and, therefore, the rate of CO2 assimilation, is influenced by both leaf anatomical factors and biochemical processes. Leaf anatomical structures act as physical barriers for CO2 transport. Biochemical processes add or remove CO2 along its diffusion pathway through mesophyll. We combined a model that quantifies the diffusive resistance for CO2 using anatomical properties, a model that partitions this resistance and an extended version of the Farquhar-von Caemmerer-Berry model. We parametrized the model by gas exchange, chlorophyll fluorescence and leaf anatomical measurements from three tomato cultivars. There was generally a good agreement between the predicted and measured light and CO2 response curves. We did a sensitivity analysis to assess how the rate of CO2 assimilation responds to changes in various leaf anatomical properties. Next, we conducted a similar analysis for assumed diffusive properties and curvature factors. Some variables (diffusion pathway length in stroma, diffusion coefficient of the stroma, curvature factors) substantially affected the predicted CO2 assimilation. We recommend more research on the measurements of these variables and on the development of 2-D and 3-D gas diffusion models, since these do not require the diffusion pathway length in the stroma as predefined parameter. PMID- 26259197 TI - The Arabidopsis lectin EULS3 is involved in stomatal closure. AB - Plants synthesize carbohydrate binding proteins in response to adverse environmental conditions such as drought, heat, pathogen attack, etc. The Arabidopsis EULS3 lectin (referred to as ArathEULS3, encoded by At2g39050) has recently been linked to the drought stress response. In this study, endogenous binding partners for this protein have been investigated. Tandem affinity purifications and mass spectrometry analyses allowed the identification of two putative interacting proteins, Embryo-specific protein 3A (ATS3A, At2g41475) and Embryo-specific protein 3B (ATS3B, At5g62200). Bimolecular fluorescence complementation experiments confirmed the interaction between ArathEULS3 and ATS3B in closed stomata of Nicotiana benthamiana plants. Transgenic lines with reduced ArathEULS3 expression exhibited an aberrant ABA-induced stomatal closure compared to plants overexpressing ArathEULS3 and control plants suggesting a role for ArathEULS3 in ABA-induced stomatal closure. Stomata are known as the major route for Pseudomonas syringae entry into the plant tissues. Bacterial infection of wild type Arabidopsis thaliana plants was accompanied by a 6-fold increase of transcript levels for ArathEULS3. Furthermore, infection experiments with ArathEULS3 overexpression lines resulted in a clear reduction of P. syringae disease symptoms whereas plants with reduced ArathEULS3 expression showed the highest levels of leaf damage at 3 days post infection. These data point towards the physiological importance of ArathEULS3 for stomatal movement. PMID- 26259198 TI - Novel proline-hydroxyproline glycopeptides from the dandelion (Taraxacum officinale Wigg.) flowers: de novo sequencing and biological activity. AB - Two novel homologous peptides named ToHyp1 and ToHyp2 that show no similarity to any known proteins were isolated from Taraxacum officinale Wigg. flowers by multidimensional liquid chromatography. Amino acid and mass spectrometry analyses demonstrated that the peptides have unusual structure: they are cysteine-free, proline-hydroxyproline-rich and post-translationally glycosylated by pentoses, with 5 carbohydrates in ToHyp2 and 10 in ToHyp1. The ToHyp2 peptide with a monoisotopic molecular mass of 4350.3Da was completely sequenced by a combination of Edman degradation and de novo sequencing via top down multistage collision induced dissociation (CID) and higher energy dissociation (HCD) tandem mass spectrometry (MS(n)). ToHyp2 consists of 35 amino acids, contains eighteen proline residues, of which 8 prolines are hydroxylated. The peptide displays antifungal activity and inhibits growth of Gram-positive and Gram-negative bacteria. We further showed that carbohydrate moieties have no significant impact on the peptide structure, but are important for antifungal activity although not absolutely necessary. The deglycosylated ToHyp2 peptide was less active against the susceptible fungus Bipolaris sorokiniana than the native peptide. Unique structural features of the ToHyp2 peptide place it into a new family of plant defense peptides. The discovery of ToHyp peptides in T. officinale flowers expands the repertoire of molecules of plant origin with practical applications. PMID- 26259200 TI - Recovery Rates of Human Fetal Skeletal Remains Using Varying Mesh Sizes. AB - Human fetal skeletal elements of different gestational ages were screened with multiple mesh sizes (6.4 mm [1/4 inch], 3.2 mm [1/8 inch], 2.0 mm, and 1.0 mm) to determine their recovery rates. All remains were previously macerated, and no significantly damaged elements were used. The 6.4 mm mesh allowed a large loss of elements (63.2% overall), including diagnostic elements, while no diagnostic elements were lost when the 1 mm mesh (0.2%) was used. When using the 3.2 mm mesh, 16.2% of the bones were lost, including some diagnostic elements (primarily tooth crowns), while 7.5% were lost using the 2.0 mm mesh. The authors recommend that the potential loss of information incurred when utilizing larger mesh sizes be taken into consideration when planning recovery methods where fetal remains may be encountered and that a minimum of 1.0 mm mesh be utilized in recovery contexts known to include fetal remains. PMID- 26259199 TI - HY5 regulates nitrite reductase 1 (NIR1) and ammonium transporter1;2 (AMT1;2) in Arabidopsis seedlings. AB - HY5 (Long Hypocotyles 5) is a key transcription factor in Arabidopsis thaliana that has a pivotal role in seedling development. Soil nitrogen is an essential macronutrient, and its uptake, assimilation and metabolism are influenced by nutrient availability and by lights. To understand the role of HY5 in nitrogen assimilation pathways, we examined the phenotype as well as the expression of selected nitrogen assimilation-related genes in hy5 mutant grown under various nitrogen limiting and nitrogen sufficient conditions, or different light conditions. We report that HY5 positively regulates nitrite reductase gene NIR1 and negatively regulates the ammonium transporter gene AMT1;2 under all nitrogen and light conditions tested, while it affects several other genes in a nitrogen supply-dependent manner. HY5 is not required for light induction of NIR1, AMT1;2 and NIA genes, but it is necessary for high level expression of NIR1 and NIA under optimal nutrient and light conditions. In addition, nitrogen deficiency exacerbates the abnormal root system of hy5. Together, our results suggest that HY5 exhibits the growth-promoting activity only when sufficient nutrients, including lights, are provided, and that HY5 has a complex involvement in nitrogen acquisition and metabolism in Arabidopsis seedlings. PMID- 26259201 TI - Impact of an innovative inpatient patient navigator program on length of stay and 30-day readmission. AB - BACKGROUND: The current climate of increasing patient complexity coupled with rising costs have prompted the need for adaptive innovation. There are limited data describing inpatient interventions targeting improvements in both communication and transitional care. OBJECTIVE: Evaluate the patient navigator (PN) program, an innovative inpatient intervention intended to enhance navigation through the complexity of hospital admissions for patients and providers. INTERVENTION: PNs were dedicated patient-care facilitators without clinical responsibilities integrated as full members of the inpatient care team responsible for enhancing communication between and among patients and providers. DESIGN: Observational retrospective cohort study. PATIENTS: All patients admitted to the general medical service between July 2010 and March 2014. SETTING: Academic medical center. MEASUREMENTS: Primary outcomes were hospital length of stay (LOS) and 30-day readmission rate matched by case mix group, age category, and resource intensity weight. RESULTS: Our matched cohort included 5628 admissions (4592 patients) exposed and 2213 admissions (1920 patients) not exposed to PNs. Admissions with PNs were 1.3 days (21%) shorter than admission without PNs (6.2 vs 7.5 days, P < 0.001). Thirty-day readmission rate was not different between the 2 groups (13.1 vs 13.8%, P = 0.48). CONCLUSION: Implementation of this intervention was associated with a reduction in LOS without an increase in 30-day readmission. PMID- 26259202 TI - An Advanced Bolus Calculator for Type 1 Diabetes: System Architecture and Usability Results. AB - This paper presents the architecture and initial usability results of an advanced insulin bolus calculator for diabetes (ABC4D), which provides personalized insulin recommendations for people with diabetes by differentiating between various diabetes scenarios and automatically adjusting its parameters over time. The proposed platform comprises two main components: a smartphone-based patient platform allowing manual input of glucose and variables affecting blood glucose levels (e.g., meal carbohydrate content and exercise) and providing real-time insulin bolus recommendations; and a clinical revision platform to supervise the automatic adaptations of the bolus calculator parameters. The system implements a previously in silico validated bolus calculator algorithm based on case-based reasoning, which uses information from similar past events (i.e., cases) to suggest improved personalized insulin bolus recommendations and automatically learns from new events. Usability of ABC4D was assessed by analyzing the system usage at the end of a six-week pilot study (n = 10). Further feedback on the use of ABC4D has been obtained from each participant at the end of the study from a usability questionnaire. On average, each participant requested 115 +/- 21 insulin recommendations, of which 103 +/- 28 (90%) were accepted. The clinical revision software proposed a total of 754 case revisions, where 723 (96%) adaptations were approved by a clinical expert and updated in the patient platform. PMID- 26259203 TI - Dynamic Threshold Analysis of Daily Oxygen Saturation for Improved Management of COPD Patients. AB - This study presents a novel dynamic threshold algorithm that is applied to daily self-measured SpO2 data for management of chronic obstructive pulmonary disease (COPD) patients in remote patient monitoring to improve accuracy of detection of exacerbation. Conventional approaches based on a fixed threshold applied to a single SpO 2 reading to detect deterioration in patient condition are known to have poor accuracy and result in high false alarm rates. This study develops and evaluates use of a dynamic threshold algorithm to reduce false alarm rates. Daily data from four COPD patients with a record of clinical interventions during the period were selected for analysis. We model the SpO2 time-series data as a combination of a trend and a stochastic component (residual). We estimate the long-term trend using a locally weighed least-squares (low-pass) filter over a long-term processing window. Results show that the time evolution of the long term trend indicated exacerbation with improved accuracy compared to a fixed threshold in our study population. Deterioration in the condition of a patient also resulted in an increase in the standard deviation of the residual (sigmares ), from 2% or less when the patient is in a healthy condition to 4% or more when condition deteriorates. Statistical analysis of the residuals showed they had a normal distribution when the condition of the patient was stable but had a long tail on the lower side during deterioration. PMID- 26259204 TI - eClims: An Extensible and Dynamic Integration Framework for Biomedical Information Systems. AB - Biomedical information systems (BIS) require consideration of three types of variability: data variability induced by new high throughput technologies, schema or model variability induced by large scale studies or new fields of research, and knowledge variability resulting from new discoveries. Beyond data heterogeneity, managing variabilities in the context of BIS requires extensible and dynamic integration process. In this paper, we focus on data and schema variabilities and we propose an integration framework based on ontologies, master data, and semantic annotations. The framework addresses issues related to: 1) collaborative work through a dynamic integration process; 2) variability among studies using an annotation mechanism; and 3) quality control over data and semantic annotations. Our approach relies on two levels of knowledge: BIS-related knowledge is modeled using an application ontology coupled with UML models that allow controlling data completeness and consistency, and domain knowledge is described by a domain ontology, which ensures data coherence. A system build with the eClims framework has been implemented and evaluated in the context of a proteomic platform. PMID- 26259205 TI - What Engineering Technology Could Do for Quality of Life in Parkinson's Disease: A Review of Current Needs and Opportunities. AB - Parkinson's disease (PD) involves well-known motor symptoms such as tremor, rigidity, bradykinesia, and altered gait, but there are also nonlocomotory motor symptoms (e.g., changes in handwriting and speech) and even nonmotor symptoms (e.g., disrupted sleep, depression) that can be measured, monitored, and possibly better managed through activity-based monitoring technologies. This will enhance quality of life (QoL) in PD through improved self-monitoring and also provide information that could be shared with a healthcare provider to help better manage treatment. Until recently, nonmotor symptoms ("soft signs") had been generally overlooked in clinical management, yet these are of primary importance to patients and their QoL. Day-to-day variability of the condition, the high variability in symptoms between patients, and the isolated snapshots of a patient in periodic clinic visits make better monitoring essential to the proper management of PD. Continuously monitored patterns of activity, social interactions, and daily activities could provide a rich source of information on status changes, guiding self-correction and clinical management. The same tools can be useful in earlier detection of PD and will improve clinical studies. Remote medical communications in the form of telemedicine, sophisticated tracking of medication use, and assistive technologies that directly compensate for disease-related challenges are examples of other near-term technology solutions to PD problems. Ultimately, a sensor technology is not good if it is not used. The Parkinson's community is a sophisticated early adopter of useful technologies and a group for which engineers can provide near-term gratifying benefits. PMID- 26259206 TI - Prediction of Freezing of Gait in Parkinson's From Physiological Wearables: An Exploratory Study. AB - Freezing of gait (FoG) is a common gait impairment among patients with advanced Parkinson's disease. FoG is associated with falls and negatively impacts the patient's quality of life. Wearable systems that detect FoG in real time have been developed to help patients resume walking by means of rhythmic cueing. Current methods focus on detection, which require FoG events to happen first, while their prediction opens the road to preemptive cueing, which might help subjects to avoid freeze altogether. We analyzed electrocardiography (ECG) and skin-conductance (SC) data from 11 subjects who experience FoG in daily life, and found statistically significant changes in ECG and SC data just before the FoG episodes, compared to normal walking. Based on these findings, we developed an anomaly-based algorithm for predicting gait freeze from relevant SC features. We were able to predict 71.3% from 184 FoG with an average of 4.2 s before a freeze episode happened. Our findings enable the possibility of wearable systems, which predict with few seconds before an upcoming FoG from SC, and start external cues to help the user avoid the gait freeze. PMID- 26259207 TI - A Computational Method to Determine Glucose Infusion Rates for Isoglycemic Intravenous Glucose Infusion Study. AB - The results of the isoglycemic intravenous glucose infusion (IIGI) study need to mimic the dynamic glucose profiles during the oral glucose tolerance test (OGTT) to accurately calculate the incretin effect. The glucose infusion rates during IIGI studies have historically been determined by experienced research personnel using the manual ad-hoc method. In this study, a computational method was developed to automatically determine the infusion rates for IIGI study based on a glucose-dynamics model. To evaluate the computational method, 18 subjects with normal glucose tolerance underwent a 75 g OGTT. One-week later, Group 1 (n = 9) and Group 2 (n = 9) underwent IIGI studies using the ad-hoc method and the computational method, respectively. Both methods were evaluated using correlation coefficient, mean absolute relative difference (MARD), and root mean square error (RMSE) between the glucose profiles from the OGTT and the IIGI study. The computational method exhibited significantly higher correlation (0.95 +/- 0.03 versus 0.86 +/- 0.10, P = 0.019), lower MARD (8.72 +/- 1.83% versus 13.11 +/- 3.66%, P = 0.002), and lower RMSE (10.33 +/- 1.99 mg/dL versus 16.84 +/- 4.43 mg/dL, P = 0.002) than the ad-hoc method. The computational method can facilitate IIGI study, and enhance its accuracy and stability. Using this computational method, a high-quality IIGI study can be accomplished without the need for experienced personnel. PMID- 26259208 TI - Information Space Receding Horizon Control for Multisensor Tasking Problems. AB - In this paper, we present a receding horizon solution to the problem of optimal scheduling for multiple sensors monitoring a group of dynamical targets. The term target is used here in the classic sense of being the object that is being sensed or observed by the sensors. This problem is motivated by the space situational awareness (SSA) problem. The multisensor optimal scheduling problem can be posed as a multiagent Markov decision process on the information space which has a dynamic programming (DP) solution. We present a simulation-based stochastic optimization technique that exploits the structure inherent in the problem to obtain variance reduction along with a distributed solution. This stochastic optimization technique is combined with a receding horizon approach which uses online solution of the control problems to obviate the need to solve the computationally intractable multiagent information space DP problem and hence, makes the technique computationally tractable. The technique is tested on a moderate scale SSA example which is nonetheless computationally intractable for existing solution techniques. PMID- 26259209 TI - View Transformation Model Incorporating Quality Measures for Cross-View Gait Recognition. AB - Cross-view gait recognition authenticates a person using a pair of gait image sequences with different observation views. View difference causes degradation of gait recognition accuracy, and so several solutions have been proposed to suppress this degradation. One useful solution is to apply a view transformation model (VTM) that encodes a joint subspace of multiview gait features trained with auxiliary data from multiple training subjects, who are different from test subjects (recognition targets). In the VTM framework, a gait feature with a destination view is generated from that with a source view by estimating a vector on the trained joint subspace, and gait features with the same destination view are compared for recognition. Although this framework improves recognition accuracy as a whole, the fit of the VTM depends on a given gait feature pair, and causes an inhomogeneously biased dissimilarity score. Because it is well known that normalization of such inhomogeneously biased scores improves recognition accuracy in general, we therefore propose a VTM incorporating a score normalization framework with quality measures that encode the degree of the bias. From a pair of gait features, we calculate two quality measures, and use them to calculate the posterior probability that both gait features originate from the same subjects together with the biased dissimilarity score. The proposed method was evaluated against two gait datasets, a large population gait dataset of over ground walking (course dataset) and a treadmill gait dataset. The experimental results show that incorporating the quality measures contributes to accuracy improvement in many cross-view settings. PMID- 26259210 TI - Robust Semi-Supervised Subspace Clustering via Non-Negative Low-Rank Representation. AB - Low-rank representation (LRR) has been successfully applied in exploring the subspace structures of data. However, in previous LRR-based semi-supervised subspace clustering methods, the label information is not used to guide the affinity matrix construction so that the affinity matrix cannot deliver strong discriminant information. Moreover, these methods cannot guarantee an overall optimum since the affinity matrix construction and subspace clustering are often independent steps. In this paper, we propose a robust semi-supervised subspace clustering method based on non-negative LRR (NNLRR) to address these problems. By combining the LRR framework and the Gaussian fields and harmonic functions method in a single optimization problem, the supervision information is explicitly incorporated to guide the affinity matrix construction and the affinity matrix construction and subspace clustering are accomplished in one step to guarantee the overall optimum. The affinity matrix is obtained by seeking a non-negative low-rank matrix that represents each sample as a linear combination of others. We also explicitly impose the sparse constraint on the affinity matrix such that the affinity matrix obtained by NNLRR is non-negative low-rank and sparse. We introduce an efficient linearized alternating direction method with adaptive penalty to solve the corresponding optimization problem. Extensive experimental results demonstrate that NNLRR is effective in semi-supervised subspace clustering and robust to different types of noise than other state-of-the-art methods. PMID- 26259211 TI - Regularity Model for Noisy Multiobjective Optimization. AB - Regularity models have been used in dealing with noise-free multiobjective optimization problems. This paper studies the behavior of a regularity model in noisy environments and argues that it is very suitable for noisy multiobjective optimization. We propose to embed the regularity model in an existing multiobjective evolutionary algorithm for tackling noises. The proposed algorithm works well in terms of both convergence and diversity. In our experimental studies, we have compared several state-of-the-art of algorithms with our proposed algorithm on benchmark problems with different levels of noises. The experimental results showed the effectiveness of the regularity model on noisy problems, but a degenerated performance on some noisy-free problems. PMID- 26259212 TI - Fast Rotation-Free Feature-Based Image Registration Using Improved N-SIFT and GMM Based Parallel Optimization. AB - Image registration is a key problem in a variety of applications, such as computer vision, medical image processing, pattern recognition, etc., while the application of registration is limited by time consumption and the accuracy in the case of large pose differences. Aimed at these two kinds of problems, we propose a fast rotation-free feature-based rigid registration method based on our proposed accelerated-NSIFT and GMM registration-based parallel optimization (PO GMMREG). Our method is accelerated by using the GPU/CUDA programming and preserving only the location information without constructing the descriptor of each interest point, while its robustness to missing correspondences and outliers is improved by converting the interest point matching to Gaussian mixture model alignment. The accuracy in the case of large pose differences is settled by our proposed PO-GMMREG algorithm by constructing a set of initial transformations. Experimental results demonstrate that our proposed algorithm can fast rigidly register 3-D medical images and is reliable for aligning 3-D scans even when they exhibit a poor initialization. PMID- 26259213 TI - Single Versus Multiple Events Error Potential Detection in a BCI-Controlled Car Game With Continuous and Discrete Feedback. AB - OBJECTIVE: This work aimed to find and evaluate a new method for detecting errors in continuous brain-computer interface (BCI) applications. Instead of classifying errors on a single-trial basis, the new method was based on multiple events (MEs) analysis to increase the accuracy of error detection. METHODS: In a BCI-driven car game, based on motor imagery (MI), discrete events were triggered whenever subjects collided with coins and/or barriers. Coins counted as correct events, whereas barriers were errors. This new method, termed ME method, combined and averaged the classification results of single events (SEs) and determined the correctness of MI trials, which consisted of event sequences instead of SEs. The benefit of this method was evaluated in an offline simulation. In an online experiment, the new method was used to detect erroneous MI trials. Such MI trials were discarded and could be repeated by the users. RESULTS: We found that, even with low SE error potential (ErrP) detection rates, feasible accuracies can be achieved when combining MEs to distinguish erroneous from correct MI trials. Online, all subjects reached higher scores with error detection than without, at the cost of longer times needed for completing the game. CONCLUSION: Findings suggest that ErrP detection may become a reliable tool for monitoring continuous states in BCI applications when combining MEs. SIGNIFICANCE: This paper demonstrates a novel technique for detecting errors in online continuous BCI applications, which yields promising results even with low single-trial detection rates. PMID- 26259214 TI - An Early Clinical Study of Time-Domain Microwave Radar for Breast Health Monitoring. AB - This study reports on monthly scans of healthy patient volunteers with the clinical prototype of a microwave imaging system. The system uses time-domain measurements, and incorporates a multistatic radar approach to imaging. It operates in the 2-4 GHz range and contains 16 wideband sensors embedded in a hemispherical dielectric radome. The system has been previously tested on tissue phantoms in controlled experiments. With this system prototype, we scanned 13 patients (26 breasts) over an eight-month period, collecting a total of 342 breast scans. The goal of the study described in this paper was to investigate how the system measurements are impacted by multiple factors that are unavoidable in monthly monitoring of human subjects. These factors include both biological variability (e.g., tissue variations due to hormonal changes or weight gain) and measurement variability (e.g., inconsistencies in patient positioning, system noise). For each patient breast, we process the results of the monthly scans to assess the variability in both the raw measured signals and in the generated images. The significance of this study is that it quantifies how much variability should be anticipated when conducting microwave breast imaging of a healthy patient over a longer period. This is an important step toward establishing the feasibility of the microwave radar imaging system for frequent monitoring of breast health. PMID- 26259215 TI - Fully Textile, PEDOT:PSS Based Electrodes for Wearable ECG Monitoring Systems. AB - GOAL: To evaluate a novel kind of textile electrodes based on woven fabrics treated with PEDOT: PSS, through an easy fabrication process, testing these electrodes for biopotential recordings. METHODS: Fabrication is based on raw fabric soaking in PEDOT: PSS using a second dopant, squeezing and annealing. The electrodes have been tested on human volunteers, in terms of both skin contact impedance and quality of the ECG signals recorded at rest and during physical activity (power spectral density, baseline wandering, QRS detectability, and broadband noise). RESULTS: The electrodes are able to operate in both wet and dry conditions. Dry electrodes are more prone to noise artifacts, especially during physical exercise and mainly due to the unstable contact between the electrode and the skin. Wet (saline) electrodes present a stable and reproducible behavior, which is comparable or better than that of traditional disposable gelled Ag/AgCl electrodes. CONCLUSION: The achieved results reveal the capability of this kind of electrodes to work without the electrolyte, providing a valuable interface with the skin, due to mixed electronic and ionic conductivity of PEDOT: PSS. These electrodes can be effectively used for acquiring ECG signals. SIGNIFICANCE: Textile electrodes based on PEDOT: PSS represent an important milestone in wearable monitoring, as they present an easy and reproducible fabrication process, very good performance in wet and dry (at rest) conditions and a superior level of comfort with respect to textile electrodes proposed so far. This paves the way to their integration into smart garments. PMID- 26259216 TI - Automatic Dissection Position Selection for Cleavage-Stage Embryo Biopsy. AB - Embryo biopsies are routinely performed for preimplantation genetic diagnosis (PGD). In order to avoid blastomere membrane rupture and cell lysis, correct selection of a suitable dissection position on the zona pellucida (ZP) is necessary. Although, the technology for automated cell manipulation has advanced greatly over the past decade, fully automated embryo biopsy in PGD has not been realized yet. Automated PGD may ultimately set a new clinical standard that improves the consistency of outcomes, increases cell survival rates, flattens the learning curve of the manual procedure, and reduces the effects of human fatigue. In this paper, we present the first approach to automatically select a suitable ZP dissection position prior to embryo biopsy from a single focused embryo image based on edge detection. The proposed method consists of a technique that estimates the elliptical ZP boundaries and another two techniques that select the suitable position for ZP dissection. These techniques achieved success rates of 96%, 94%, and 94% respectively. In addition, the proposed ZP boundary estimation technique has the potential to perform ZP thickness variation (ZPTV) test and other ZP morphology measurements with further improvement in the future. Our methods provide a starting point for fast position selection prior to automatic embryo biopsy. PMID- 26259217 TI - Spline Driven: High Accuracy Projectors for Tomographic Reconstruction From Few Projections. AB - Tomographic iterative reconstruction methods need a very thorough modeling of data. This point becomes critical when the number of available projections is limited. At the core of this issue is the projector design, i.e., the numerical model relating the representation of the object of interest to the projections on the detector. Voxel driven and ray driven projection models are widely used for their short execution time in spite of their coarse approximations. Distance driven model has an improved accuracy but makes strong approximations to project voxel basis functions. Cubic voxel basis functions are anisotropic, accurately modeling their projection is, therefore, computationally expensive. Both smoother and more isotropic basis functions better represent the continuous functions and provide simpler projectors. These considerations have led to the development of spherically symmetric volume elements, called blobs. Set apart their isotropy, blobs are often considered too computationally expensive in practice. In this paper, we consider using separable B-splines as basis functions to represent the object, and we propose to approximate the projection of these basis functions by a 2D separable model. When the degree of the B-splines increases, their isotropy improves and projections can be computed regardless of their orientation. The degree and the sampling of the B-splines can be chosen according to a tradeoff between approximation quality and computational complexity. We quantitatively measure the good accuracy of our model and compare it with other projectors, such as the distance-driven and the model proposed by Long et al. From the numerical experiments, we demonstrate that our projector with an improved accuracy better preserves the quality of the reconstruction as the number of projections decreases. Our projector with cubic B-splines requires about twice as many operations as a model based on voxel basis functions. Higher accuracy projectors can be used to improve the resolution of the existing systems, or to reduce the number of projections required to reach a given resolution, potentially reducing the dose absorbed by the patient. PMID- 26259218 TI - Cross-Modal Subspace Learning via Pairwise Constraints. AB - In multimedia applications, the text and image components in a web document form a pairwise constraint that potentially indicates the same semantic concept. This paper studies cross-modal learning via the pairwise constraint and aims to find the common structure hidden in different modalities. We first propose a compound regularization framework to address the pairwise constraint, which can be used as a general platform for developing cross-modal algorithms. For unsupervised learning, we propose a multi-modal subspace clustering method to learn a common structure for different modalities. For supervised learning, to reduce the semantic gap and the outliers in pairwise constraints, we propose a cross-modal matching method based on compound l21 regularization. Extensive experiments demonstrate the benefits of joint text and image modeling with semantically induced pairwise constraints, and they show that the proposed cross-modal methods can further reduce the semantic gap between different modalities and improve the clustering/matching accuracy. PMID- 26259219 TI - An Iterative CT Reconstruction Algorithm for Fast Fluid Flow Imaging. AB - The study of fluid flow through solid matter by computed tomography (CT) imaging has many applications, ranging from petroleum and aquifer engineering to biomedical, manufacturing, and environmental research. To avoid motion artifacts, current experiments are often limited to slow fluid flow dynamics. This severely limits the applicability of the technique. In this paper, a new iterative CT reconstruction algorithm for improved a temporal/spatial resolution in the imaging of fluid flow through solid matter is introduced. The proposed algorithm exploits prior knowledge in two ways. First, the time-varying object is assumed to consist of stationary (the solid matter) and dynamic regions (the fluid flow). Second, the attenuation curve of a particular voxel in the dynamic region is modeled by a piecewise constant function over time, which is in accordance with the actual advancing fluid/air boundary. Quantitative and qualitative results on different simulation experiments and a real neutron tomography data set show that, in comparison with the state-of-the-art algorithms, the proposed algorithm allows reconstruction from substantially fewer projections per rotation without image quality loss. Therefore, the temporal resolution can be substantially increased, and thus fluid flow experiments with faster dynamics can be performed. PMID- 26259220 TI - Modeling, Prediction, and Reduction of 3D Crosstalk in Circular Polarized Stereoscopic LCDs. AB - Crosstalk, which is the incomplete separation between the left and right views in 3D displays, induces ghosting and causes difficulty of the eyes to fuse the stereo image for depth perception. Circularly polarized (CP) liquid crystal display (LCD) is one of the main-stream consumer 3D displays with the prospering of 3D movies and gamings. The polarizing system including the patterned retarder is one of the major causes of crosstalk in CP LCD. The contributions of this paper are the modeling of the polarizing system of CP LCD, and a crosstalk reduction method that efficiently cancels crosstalk and preserves image contrast. For the modeling, the practical orientation of the polarized glasses (PG) is considered. In addition, this paper calculates the rotation of the light propagation coordinate for the Stokes vector as light propagates from LCD to PG, and this calculation is missing in the previous works when applying Mueller calculus. The proposed crosstalk reduction method is formulated as a linear programming problem, which can be easily solved. In addition, we propose excluding the highly textured areas in the input images to further preserve image contrast in crosstalk reduction. PMID- 26259221 TI - Relevance Metric Learning for Person Re-Identification by Exploiting Listwise Similarities. AB - Person re-identification aims to match people across non-overlapping camera views, which is an important but challenging task in video surveillance. In order to obtain a robust metric for matching, metric learning has been introduced recently. Most existing works focus on seeking a Mahalanobis distance by employing sparse pairwise constraints, which utilize image pairs with the same person identity as positive samples, and select a small portion of those with different identities as negative samples. However, this training strategy has abandoned a large amount of discriminative information, and ignored the relative similarities. In this paper, we propose a novel relevance metric learning method with listwise constraints (RMLLCs) by adopting listwise similarities, which consist of the similarity list of each image with respect to all remaining images. By virtue of listwise similarities, RMLLC could capture all pairwise similarities, and consequently learn a more discriminative metric by enforcing the metric to conserve predefined similarity lists in a low-dimensional projection subspace. Despite the performance enhancement, RMLLC using predefined similarity lists fails to capture the relative relevance information, which is often unavailable in practice. To address this problem, we further introduce a rectification term to automatically exploit the relative similarities, and develop an efficient alternating iterative algorithm to jointly learn the optimal metric and the rectification term. Extensive experiments on four publicly available benchmarking data sets are carried out and demonstrate that the proposed method is significantly superior to the state-of-the-art approaches. The results also show that the introduction of the rectification term could further boost the performance of RMLLC. PMID- 26259222 TI - Global neural dynamic surface tracking control of strict-feedback systems with application to hypersonic flight vehicle. AB - This paper studies both indirect and direct global neural control of strict feedback systems in the presence of unknown dynamics, using the dynamic surface control (DSC) technique in a novel manner. A new switching mechanism is designed to combine an adaptive neural controller in the neural approximation domain, together with the robust controller that pulls the transient states back into the neural approximation domain from the outside. In comparison with the conventional control techniques, which could only achieve semiglobally uniformly ultimately bounded stability, the proposed control scheme guarantees all the signals in the closed-loop system are globally uniformly ultimately bounded, such that the conventional constraints on initial conditions of the neural control system can be relaxed. The simulation studies of hypersonic flight vehicle (HFV) are performed to demonstrate the effectiveness of the proposed global neural DSC design. PMID- 26259223 TI - CPG Network Optimization for a Biomimetic Robotic Fish via PSO. AB - In this brief, we investigate the parameter optimization issue of a central pattern generator (CPG) network governed forward and backward swimming for a fully untethered, multijoint biomimetic robotic fish. Considering that the CPG parameters are tightly linked to the propulsive performance of the robotic fish, we propose a method for determination of relatively optimized control parameters. Within the framework of evolutionary computation, we use a combination of dynamic model and particle swarm optimization (PSO) algorithm to seek the CPG characteristic parameters for an enhanced performance. The PSO-based optimization scheme is validated with extensive experiments conducted on the actual robotic fish. Noticeably, the optimized results are shown to be superior to previously reported forward and backward swimming speeds. PMID- 26259224 TI - Dynamical Behavior of Delayed Reaction-Diffusion Hopfield Neural Networks Driven by Infinite Dimensional Wiener Processes. AB - In this paper, we focus on the long time behavior of the mild solution to delayed reaction-diffusion Hopfield neural networks (DRDHNNs) driven by infinite dimensional Wiener processes. We analyze the existence, uniqueness, and stability of this system under the local Lipschitz function by constructing an appropriate Lyapunov-Krasovskii function and utilizing the semigroup theory. Some easy-to test criteria affecting the well-posedness and stability of the networks, such as infinite dimensional noise and diffusion effect, are obtained. The criteria can be used as theoretic guidance to stabilize DRDHNNs in practical applications when infinite dimensional noise is taken into consideration. Meanwhile, considering the fact that the standard Brownian motion is a special case of infinite dimensional Wiener process, we undertake an analysis of the local Lipschitz condition, which has a wider range than the global Lipschitz condition. Two samples are given to examine the availability of the results in this paper. Simulations are also given using the MATLAB. PMID- 26259225 TI - Analyzing Activity Behavior and Movement in a Naturalistic Environment Using Smart Home Techniques. AB - One of the many services that intelligent systems can provide is the ability to analyze the impact of different medical conditions on daily behavior. In this study, we use smart home and wearable sensors to collect data, while ( n = 84) older adults perform complex activities of daily living. We analyze the data using machine learning techniques and reveal that differences between healthy older adults and adults with Parkinson disease not only exist in their activity patterns, but that these differences can be automatically recognized. Our machine learning classifiers reach an accuracy of 0.97 with an area under the ROC curve value of 0.97 in distinguishing these groups. Our permutation-based testing confirms that the sensor-based differences between these groups are statistically significant. PMID- 26259226 TI - A Temperature-Based Bioimpedance Correction for Water Loss Estimation During Sports. AB - The amount of total body water (TBW) can be estimated based on bioimpedance measurements of the human body. In sports, TBW estimations are of importance because mild water losses can impair muscular strength and aerobic endurance. Severe water losses can even be life threatening. TBW estimations based on bioimpedance, however, fail during sports because the increased body temperature corrupts bioimpedance measurements. Therefore, this paper proposes a machine learning method that eliminates the effects of increased temperature on bioimpedance and, consequently, reveals the changes in bioimpedance that are due to TBW loss. This is facilitated by utilizing changes in skin and core temperature. The method was evaluated in a study in which bioimpedance, temperature, and TBW loss were recorded every 15 min during a 2-h running workout. The evaluation demonstrated that the proposed method is able to reduce the error of TBW loss estimation by up to 71%, compared to the state of art. In the future, the proposed method in combination with portable bioimpedance devices might facilitate the development of wearable systems for continuous and noninvasive TBW loss monitoring during sports. PMID- 26259227 TI - Synchronous Hybrid Event- and Time-Driven Consensus in Multiagent Networks With Time Delays. AB - This paper studies the delay robustness of a class of synchronous hybrid event- and time-driven consensus protocols in undirected networks. These protocols can ensure the system performance at reduced data-sampling rates. We consider three types of time delays in feedbacks, including one common time delay, multiple time invariant delays, and multiple time-varying delays; and by sampled-data control techniques, we characterize the maximum allowable time delay and the event detecting period for solving the average consensus problem in terms of the algebraic structure of interaction topologies. Simulations are given to show the effectiveness of theoretical results. PMID- 26259228 TI - Learning Stationary Correlated Equilibria in Constrained General-Sum Stochastic Games. AB - We study constrained general-sum stochastic games with unknown Markovian dynamics. A distributed constrained no-regret Q -learning scheme (CNR Q ) is presented to guarantee convergence to the set of stationary correlated equilibria of the game. Prior art addresses the unconstrained case only, is structured with nested control loops, and has no convergence result. CNR Q is cast as a single loop three-timescale asynchronous stochastic approximation algorithm with set valued update increments. A rigorous convergence analysis with differential inclusion arguments is given which draws on recent extensions of the theory of stochastic approximation to the case of asynchronous recursive inclusions with set-valued mean fields. Numerical results are given for the exemplary application of CNR Q to decentralized resource control in heterogeneous wireless networks. PMID- 26259229 TI - Discriminative Hash Tracking With Group Sparsity. AB - In this paper, we propose a novel tracking framework based on discriminative supervised hashing algorithm. Different from previous methods, we treat tracking as a problem of object matching in a binary space. Using the hash functions, all target templates and candidates are mapped into compact binary codes, with which the target matching is conducted effectively. To be specific, we make full use of the label information to assign a compact and discriminative binary code for each sample. And to deal with out-of-sample case, multiple hash functions are trained to describe the learned binary codes, and group sparsity is introduced to the hash projection matrix to select the representative and discriminative features dynamically, which is crucial for the tracker to adapt to target appearance variations. The whole training problem is formulated as an optimization function where the hash codes and hash function are learned jointly. Extensive experiments on various challenging image sequences demonstrate the effectiveness and robustness of the proposed tracker. PMID- 26259230 TI - Excitatory and inhibitory conversive experiences: neurobiological features involving positive and negative conversion symptoms. AB - Previous reviews have focused on neurobiological and physiological mechanisms underlying conversion disorder, but they do not usually distinguish between negative and positive conversion symptoms. Some authors have proposed that different phenomena should underlie both situations and that diverse emotion regulation strategies (under- vs. overregulation of affect) should be related to different internal experiences (excitatory experiences with hyperarousal manifestations vs. inhibitory experiences coexisting with hypoarousal states, respectively). After a careful review of the literature, we conclude that there is not a unique theory comprising all findings. Nevertheless, we have also collected some replicated findings that should be salient. Patients manifesting positive conversion symptoms tended to present with limbic hyperfunction, not sufficiently counteracted by prefrontal control. This leads to underregulation of affect mechanisms, increased emotional reactivity and autonomic hyperarousal. The opposite pattern (with a prefrontal overfunction working as a cognitive brake over the limbic system) has been described during negative conversion manifestations. We also highlight the influence of fronto-limbic circuits over cortico-striato-thalamo-cortical circuits' regulation, whose horizontal and vertical synchronization has been at the spotlight of the genesis of conversion and dissociative disorders. PMID- 26259231 TI - Possible anti-diarrhoeal potential of ethanol leaf extract of Chromolaena odorata in castor oil-induced rats. AB - BACKGROUND: Chromolaena odorata is a plant commonly used traditionally to treat ailments including diarrhoea in Nigeria. METHODS: The ethanol leaf extract of C. odorata was studied for its anti-diarrhoeal activity using electrolyte test and castor oil-induced diarrhoea rats' models. Acute toxicity effect of the extract was also evaluated. RESULTS: The extract showed a dose-dependent protection against castor oil-induced diarrhoea at the tested doses (200 and 400 mg/kg body weights). The protection offered by pretreatment with 400 mg/kg body weight of the ethanol leaf extract of C. odorata with regards to reductions in the incidences of faecal wetness and rate of defaecations were statistically comparable to that achieved with Lomotil, a known anti-diarrhoeic drug. The result of the electrolyte test showed that the extract pretreated groups had significantly (p<0.05) lower potassium and sodium ions in their intestinal fluid when compared with the diarrhoeic untreated controls. This is well tolerated. CONCLUSIONS: The results indicate that the ethanol leaf extract of C. odorata is safe and possesses anti-diarrhoeal activity with electrolyte reabsorption proposed as the possible mechanism of action. PMID- 26259232 TI - Dietary supplementation with green tea extract promotes enhanced human leukocyte activity. AB - BACKGROUND: Leukocytes play a vital role in the host defence and inflammatory systems, the latter being responsible for the pathogenesis of a wide spectrum of acute and chronic diseases. Green tea is a popular beverage, which is consumed worldwide and its active ingredients are epicatechin derivatives, which possess distinct anti-inflammatory properties. The purpose of this study was to investigate if a green tea extract could enhance leukocyte function in humans. METHODS: Volunteers were asked to take 300 mg of the green tea extract daily for 14 days and the capacity of circulating leukocytes to release both myeloperoxidase and lactoferrin was assessed. Whole blood from volunteers was stimulated with the bacterial peptide Formyl-Methionine-Leucine-Phenylalanine (fMet-Leu-Phe). Myeloperoxidase an enzyme that converts hydrogen peroxide to hypochlorous acid and is stored and secreted from the granules of neutrophils and monocytes and was measured as well as lactoferrin which is an iron-binding protein stored and secreted from the neutrophils. In conjunction the antioxidant capacity of the blood of the volunteers was also determined using a chemiluminescence method that measures the capacity of plasma to scavenge superoxide. RESULTS: After 14 days of treatment there was a significant increase in the release of myeloperoxidase and lactoferrin when whole blood was stimulated with fMet-Leu-Phe (p<0.05), which activates a number of leukocytes including mature neutrophils and monocytes. This was mirrored by a significant increase in the total antioxidant status after 14 days of green tea ingestion (p0.05). After the "wash-out" period of 4 weeks, all parameters were consistent with those observed at the start of the trial (day 0). Treatment with the green tea extract also caused a slight but non-significant decrease in the number of circulating leukocytes, but the counts remained within published "normal" ranges for healthy human adults. CONCLUSIONS: This study indicates that a green tea extract when taken as a dietary supplement for 14 days can increase the leukocyte activity and the total plasma antioxidant status and may have role to play in the prevention of inflammatory disease. PMID- 26259233 TI - From the conventional to the alternative: exploring patients' pathways of cancer treatment and care. AB - BACKGROUND: Complementary and alternative medicine (CAM) use is widespread and on the increase among cancer patients. Most research to date has involved a cross sectional snapshot of CAM use rather than an exploration into the longitudinal, nonlinear treatment trajectories that cancer patients develop. Our aim is to explore and describe different treatment and decision-making pathways that individuals develop after receipt of a diagnosis of either breast, colorectal, or prostate cancer. METHODS: The study was part of a larger mixed-methods pilot project to explore the feasibility of conducting a five-year international study to assess cancer patients' treatment pathways, including health care use and the perceived impact of different patterns of use on health outcomes over the course of one year. The results presented in this paper are based on the analysis of personal interviews that were conducted over the course of 12 months with 30 participants. RESULTS: Five pathways emerged from the data: passive conventional, self-directed conventional, cautious integrative, aggressive integrative, and aggressive alternative. Factors that shaped each pathway included health beliefs, decision-making role, illness characteristics, and the patient-practitioner relationship. CONCLUSIONS: The results of this examination of the longitudinal treatment and decision-making trajectory provide important information to support health care professionals in their quest for individualized, targeted support at each stage of the patient pathway. PMID- 26259234 TI - Mouse models of liver cancer: Progress and recommendations. AB - To clarify the pathogenesis of hepatocellular carcinoma (HCC) and investigate the effects of potential therapies, a number of mouse models have been developed. Subcutaneous xenograft models are widely used in the past decades. Yet, with the advent of in vivo imaging technology, investigators are more and more concerned with the orthotopic models nowadays. Genetically engineered mouse models (GEM) have greatly facilitated studies of gene function in HCC development. Recently, GEM of miR-122 and miR-221 provided new approaches for better understanding of the in vivo functions of microRNA in hepatocarcinogenesis. Chemically induced liver tumors in animals share many of the morphological, histogenic, and biochemical features of human HCC. Yet, the complicated and obscure genomic alternation restricts their applications. In this review, we highlight both the frequently used mouse models and some emerging ones with emphasis on their merits or defects, and give advises for investigators to chose a "best-fit" animal model in HCC research. PMID- 26259235 TI - PERK/CHOP contributes to the CGK733-induced vesicular calcium sequestration which is accompanied by non-apoptotic cell death. AB - Calcium ions (Ca(2+)) are indispensable for the physiology of organisms and the molecular regulation of cells. We observed that CGK733, a synthetic chemical substance, induced non-apoptotic cell death and stimulated reversible calcium sequestration by vesicles in pancreatic cancer cells. The endoplasmic reticulum (ER) stress eukaryotic translation initiation factor 2-alpha kinase 3/C/EBP homologous protein (PERK/CHOP) signaling pathway was shown to be activated by treatment with CGK733. Ionomycin, an ER stress drug and calcium ionophore, can activate PERK/CHOP signaling and accelerate CGK733-induced calcium sequestration. Knockdown of CHOP diminished CGK733-induced vesicular calcium sequestration, but had no effects on the cell death. Proteomic analysis demonstrated that the ER located calcium-binding proteins, calumenin and protein S100-A11, were altered in CGK733-treated cells compared to non-treated controls. Our study reveals that CGK733-induced intracellular calcium sequestration is correlated with the PERK/CHOP signaling pathway and may also be involved in the dysregulations of calcium-binding proteins. PMID- 26259236 TI - Tumorigenesis by Meis1 overexpression is accompanied by a change of DNA target sequence specificity which allows binding to the AP-1 element. AB - Meis1 overexpression induces tumorigenicity but its activity is inhibited by Prep1 tumor suppressor. Why does overexpression of Meis1 cause cancer and how does Prep1 inhibit? Tumor profiling and ChIP-sequencing data in a genetically defined set of cell lines show that: 1) The number of Meis1 and Prep1 DNA binding sites increases linearly with their concentration resulting in a strong increase of "extra" target genes. 2) At high concentration, Meis1 DNA target specificity changes such that the most enriched consensus becomes that of the AP-1 regulatory element, whereas the specific OCTA consensus is not enriched because diluted within the many extra binding sites. 3) Prep1 inhibits Meis1 tumorigenesis preventing the binding to many of the "extra" genes containing AP-1 sites. 4) The overexpression of Prep1, but not of Meis1, changes the functional genomic distribution of the binding sites, increasing seven fold the number of its "enhancer" and decreasing its "promoter" targets. 5) A specific Meis1 "oncogenic" and Prep1 "tumor suppressing" signature has been identified selecting from the pool of genes bound by each protein those whose expression was modified uniquely by the "tumor-inducing" Meis1 or tumor-inhibiting Prep1 overexpression. In both signatures, the enriched gene categories are the same and are involved in signal transduction. However, Meis1 targets stimulatory genes while Prep1 targets genes that inhibit the tumorigenic signaling pathways. PMID- 26259237 TI - Inverse expression of somatostatin and CXCR4 chemokine receptors in gastroenteropancreatic neuroendocrine neoplasms of different malignancy. AB - INTRODUCTION: Somatostatin receptors (SSTR) are widely distributed in well differentiated neuroendocrine neoplasms (NEN) and serve as primary targets for diagnostics and treatment. An overexpression of the chemokine receptor CXCR4, in contrast, is considered to be present mainly in highly proliferative and advanced tumors. Comparative data are still lacking, however, for neuroendocrine carcinomas (NEC). METHODS: SSTR subtype (1, 2A, 3, 5) and CXCR4 expression was evaluated in G1 (n = 31), G2 (n = 47), and low (G3a; Ki-67: 21-49%; n = 21) and highly proliferative (G3b; Ki-67: >50%, n = 22) G3 (total n = 43) gastroenteropancreatic NEN samples by performing immunohistochemistry with monoclonal rabbit anti-human anti-SSTR and anti-CXCR4 antibodies, respectively, and was correlated with clinical data. RESULTS: Both CXCR4 and SSTR were widely expressed in all tumors investigated. CXCR4 expression differed significantly between the G1 and G3 specimens and within the G3 group (G3a to G3b), and was positively correlated with Ki-67 expression. SSTR2A, in contrast, exhibited an inverse association with Ki-67. SSTR2A was highly expressed in G1 and G2 tumors, but was significantly less abundant in G3 carcinomas. Additionally, SSTR1 expression was higher in G3a than in G3b tumors. CONCLUSION: We observed an elevation in CXCR4 and a decrease in SSTR2A expression with increasing malignancy. Interestingly, 23% of the G3 specimens had strong SSTR2A expression. Because CXCR4 was strongly expressed in highly proliferative G3 carcinomas, it is an interesting new target and needs to be validated in larger studies. PMID- 26259238 TI - MicroRNA in pancreatic adenocarcinoma: predictive/prognostic biomarkers or therapeutic targets? AB - Pancreatic ductal adenocarcinoma (PDAC) is a tumor with a poor prognosis, short overall survival and few chemotherapeutic choices. MicroRNAs (miRNAs) are non coding, single-stranded RNAs of around 22 nucleotides involved in the pathogenic mechanisms of carcinogenesis and metastasis. They have been studied in many tumors in order to identify potential diagnostic, prognostic or therapeutic targets. In the current literature, many studies have analyzed the role of miRNAs in PDAC. In fact, the absence of appropriate biomarkers, the difficultly of early detection of this tumor, and the lack of effective chemotherapy in patients with unresectable disease have focused attention on miRNAs as new, interesting advance in this malignancy. In this review we analyzed the role of miRNAs in PDAC in order to understand the mechanisms of action and the difference between the onco miRNA and the tumor suppressor miRNA. We also reviewed all the data related to the use of these molecules as predictive as well as prognostic biomarkers in the course of the disease. Finally, the possible therapeutic use of miRNAs or anti miRNAs in PDAC is also discussed. In conclusion, although there is still no clinical application for these molecules in PDAC, it is our opinion that the preclinical evidence of the role of specific miRNAs in carcinogenesis, the possibility of using miRNAs as diagnostic or prognostic biomarkers, and their potential therapeutic role, warrant future studies in PDAC. PMID- 26259241 TI - DALSA: Domain Adaptation for Supervised Learning From Sparsely Annotated MR Images. AB - We propose a new method that employs transfer learning techniques to effectively correct sampling selection errors introduced by sparse annotations during supervised learning for automated tumor segmentation. The practicality of current learning-based automated tissue classification approaches is severely impeded by their dependency on manually segmented training databases that need to be recreated for each scenario of application, site, or acquisition setup. The comprehensive annotation of reference datasets can be highly labor-intensive, complex, and error-prone. The proposed method derives high-quality classifiers for the different tissue classes from sparse and unambiguous annotations and employs domain adaptation techniques for effectively correcting sampling selection errors introduced by the sparse sampling. The new approach is validated on labeled, multi-modal MR images of 19 patients with malignant gliomas and by comparative analysis on the BraTS 2013 challenge data sets. Compared to training on fully labeled data, we reduced the time for labeling and training by a factor greater than 70 and 180 respectively without sacrificing accuracy. This dramatically eases the establishment and constant extension of large annotated databases in various scenarios and imaging setups and thus represents an important step towards practical applicability of learning-based approaches in tissue classification. PMID- 26259242 TI - Robust Visual Tracking via Sparsity-Induced Subspace Learning. AB - Target representation is a necessary component for a robust tracker. However, during tracking, many complicated factors may make the accumulated errors in the representation significantly large, leading to tracking drift. This paper aims to improve the robustness of target representation to avoid the influence of the accumulated errors, such that the tracker only acquires the information that facilitates tracking and ignores the distractions. We observe that the locally mutual relations between the feature observations of temporally obtained targets are beneficial to the subspace representation in visual tracking. Thus, we propose a novel subspace learning algorithm for visual tracking, which imposes joint row-wise sparsity structure on the target subspace to adaptively exclude distractive information. The sparsity is induced by exploiting the locally mutual relations between the feature observations during learning. To this end, we formulate tracking as a subspace sparsity inducing problem. A large number of experiments on various challenging video sequences demonstrate that our tracker outperforms many other state-of-the-art trackers. PMID- 26259243 TI - Resampling Images to a Regular Grid From a Non-Regular Subset of Pixel Positions Using Frequency Selective Reconstruction. AB - Even though image signals are typically defined on a regular 2D grid, there also exist many scenarios where this is not the case and the amplitude of the image signal only is available for a non-regular subset of pixel positions. In such a case, a resampling of the image to a regular grid has to be carried out. This is necessary since almost all algorithms and technologies for processing, transmitting or displaying image signals rely on the samples being available on a regular grid. Thus, it is of great importance to reconstruct the image on this regular grid, so that the reconstruction comes closest to the case that the signal has been originally acquired on the regular grid. In this paper, Frequency Selective Reconstruction is introduced for solving this challenging task. This algorithm reconstructs image signals by exploiting the property that small areas of images can be represented sparsely in the Fourier domain. By further considering the basic properties of the optical transfer function of imaging systems, a sparse model of the signal is iteratively generated. In doing so, the proposed algorithm is able to achieve a very high reconstruction quality, in terms of peak signal-to-noise ratio (PSNR) and structural similarity measure as well as in terms of visual quality. The simulation results show that the proposed algorithm is able to outperform state-of-the-art reconstruction algorithms and gains of more than 1 dB PSNR are possible. PMID- 26259240 TI - A comparative analysis of inhibitors of the glycolysis pathway in breast and ovarian cancer cell line models. AB - Many cancer cells rely on aerobic glycolysis for energy production and targeting of this pathway is a potential strategy to inhibit cancer cell growth. In this study, inhibition of five glycolysis pathway molecules (GLUT1, HKII, PFKFB3, PDHK1 and LDH) using 9 inhibitors (Phloretin, Quercetin, STF31, WZB117, 3PO, 3 bromopyruvate, Dichloroacetate, Oxamic acid, NHI-1) was investigated in panels of breast and ovarian cancer cell line models. All compounds tested blocked glycolysis as indicated by increased extracellular glucose and decreased lactate production and also increased apoptosis. Sensitivity to several inhibitors correlated with the proliferation rate of the cell lines. Seven compounds had IC50 values that were associated with each other consistent with a shared mechanism of action. A synergistic interaction was revealed between STF31 and Oxamic acid when combined with the antidiabetic drug metformin. Sensitivity to glycolysis inhibition was also examined under a range of O2 levels (21% O2, 7% O2, 2% O2 and 0.5% O2) and greater resistance to the inhibitors was found at low oxygen conditions (7% O2, 2% O2 and 0.5% O2) relative to 21% O2 conditions. These results indicate growth of breast and ovarian cancer cell lines is dependent on all the targets examined in the glycolytic pathway with increased sensitivity to the inhibitors under normoxic conditions. PMID- 26259239 TI - Evaluation of carbonic anhydrase IX as a therapeutic target for inhibition of breast cancer invasion and metastasis using a series of in vitro breast cancer models. AB - Triple negative, resistant or metastatic disease are major factors in breast cancer mortality, warranting novel approaches. Carbonic anhydrase IX (CAIX) is implicated in survival, migration and invasion of breast cancer cells and inhibition provides an innovative therapeutic strategy. The efficacy of 5 novel ureido-substituted sulfamate CAIX inhibitors were assessed in increasingly complex breast cancer models, including cell lines in normoxia and hypoxia, 3D spheroids and an ex-vivo explant model utilizing fresh biopsy tissue from different breast cancer subtypes. CAIX expression was evaluated in a tissue microarray (TMA) of 92 paired lymph node and primary breast cancers and 2 inhibitors were appraised in vivo using MDA-MB-231 xenografts. FC11409B, FC9398A, FC9403, FC9396A and S4 decreased cell proliferation and migration and inhibited 3D spheroid invasion. S4, FC9398A and FC9403A inhibited or prevented invasion into collagen. FC9403A significantly reversed established invasion whilst FC9398A and DTP348 reduced xenograft growth. TMA analysis showed increased CAIX expression in triple negative cancers. These data establish CAIX inhibition as a relevant therapeutic goal in breast cancer, targeting the migratory, invasive, and metastatic potential of this disease. The use of biopsy tissue suggests efficacy against breast cancer subtypes, and should provide a useful tool in drug testing against invasive cancers. PMID- 26259244 TI - Bayesian Inference for Neighborhood Filters With Application in Denoising. AB - Range-weighted neighborhood filters are useful and popular for their edge preserving property and simplicity, but they are originally proposed as intuitive tools. Previous works needed to connect them to other tools or models for indirect property reasoning or parameter estimation. In this paper, we introduce a unified empirical Bayesian framework to do both directly. A neighborhood noise model is proposed to reason and infer the Yaroslavsky, bilateral, and modified non-local means filters by joint maximum a posteriori and maximum likelihood estimation. Then, the essential parameter, range variance, can be estimated via model fitting to the empirical distribution of an observable chi scale mixture variable. An algorithm based on expectation-maximization and quasi-Newton optimization is devised to perform the model fitting efficiently. Finally, we apply this framework to the problem of color-image denoising. A recursive fitting and filtering scheme is proposed to improve the image quality. Extensive experiments are performed for a variety of configurations, including different kernel functions, filter types and support sizes, color channel numbers, and noise types. The results show that the proposed framework can fit noisy images well and the range variance can be estimated successfully and efficiently. PMID- 26259245 TI - Constrained Multi-View Video Face Clustering. AB - In this paper, we focus on face clustering in videos. To promote the performance of video clustering by multiple intrinsic cues, i.e., pairwise constraints and multiple views, we propose a constrained multi-view video face clustering method under a unified graph-based model. First, unlike most existing video face clustering methods which only employ these constraints in the clustering step, we strengthen the pairwise constraints through the whole video face clustering framework, both in sparse subspace representation and spectral clustering. In the constrained sparse subspace representation, the sparse representation is forced to explore unknown relationships. In the constrained spectral clustering, the constraints are used to guide for learning more reasonable new representations. Second, our method considers both the video face pairwise constraints as well as the multi-view consistence simultaneously. In particular, the graph regularization enforces the pairwise constraints to be respected and the co regularization penalizes the disagreement among different graphs of multiple views. Experiments on three real-world video benchmark data sets demonstrate the significant improvements of our method over the state-of-the-art methods. PMID- 26259246 TI - A Mobile Kalman-Filter Based Solution for the Real-Time Estimation of Spatio Temporal Gait Parameters. AB - Gait impairments are among the most disabling symptoms in several musculoskeletal and neurological conditions, severely limiting personal autonomy. Wearable gait sensors have been attracting attention as diagnostic tool for gait and are emerging as promising tool for tutoring and guiding gait execution. If their popularity is continuously growing, still there is room for improvement, especially towards more accurate solutions for spatio-temporal gait parameters estimation. We present an implementation of a zero-velocity-update gait analysis system based on a Kalman filter and off-the-shelf shoe-worn inertial sensors. The algorithms for gait events and step length estimation were specifically designed to comply with pathological gait patterns. More so, an Android app was deployed to support fully wearable and stand-alone real-time gait analysis. Twelve healthy subjects were enrolled to preliminarily tune the algorithms; afterwards sixteen persons with Parkinson's disease were enrolled for a validation study. Over the 1314 strides collected on patients at three different speeds, the total root mean square difference on step length estimation between this system and a gold standard was 2.9%. This shows that the proposed method allows for an accurate gait analysis and paves the way to a new generation of mobile devices usable anywhere for monitoring and intervention. PMID- 26259247 TI - Prior-to- and Post-Impact Fall Detection Using Inertial and Barometric Altimeter Measurements. AB - This paper investigates a fall detection system based on the integration of an inertial measurement unit with a barometric altimeter (BIMU). The vertical motion of the body part the BIMU was attached to was monitored on-line using a method that delivered drift-free estimates of the vertical velocity and estimates of the height change from the floor. The experimental study included activities of daily living of seven types and falls of five types, simulated by a cohort of 25 young healthy adults. The downward vertical velocity was thresholded at 1.38 m/s, yielding 80% sensitivity (SE), 100% specificity (SP) and a mean prior-to-impact time of 157 ms (range 40-300 ms). The soft falls, i.e., those with downward vertical velocity above 0.55 m/s and below 1.38 m/s were analyzed post-impact. Six fall detection methods, tuned to achieve 100% SE, were considered to include features of impact, change of posture and height, singularly or in association with one another. No single feature allowed for 100% SP. The detection accuracy marginally improved when the height change was considered in association with either the impact or the change of posture; the post-impact fall detection method that analyzed the impact and the change of posture together achieved 100% SP. PMID- 26259248 TI - Spatial Memory for Patterns of Taps on the Fingers. AB - Ongoing development of haptic technology has the potential to provide significant improvement in safety and performance in demanding environments where vision and hearing are compromised. Research regarding the cognitive psychology of touch is lacking and could be beneficial in the development of expectations about human performance for the refinement and implementation of haptic technology. This study examines haptic-spatial memory using a novel assessment method based on finger anatomy. In addition, evidence is presented for a serial-position effect for haptic-spatial memory that is analogous to the classic serial-position effect demonstrated in the verbal recall of word lists. Finally, haptic-spatial memory is compared with short- and long-term memory for visual-spatial tasks. PMID- 26259249 TI - Control of Large-Scale Boolean Networks via Network Aggregation. AB - A major challenge to solve problems in control of Boolean networks is that the computational cost increases exponentially when the number of nodes in the network increases. We consider the problem of controllability and stabilizability of Boolean control networks, address the increasing cost problem by partitioning the network graph into several subnetworks, and analyze the subnetworks separately. Easily verifiable necessary conditions for controllability and stabilizability are proposed for a general aggregation structure. For acyclic aggregation, we develop a sufficient condition for stabilizability. It dramatically reduces the computational complexity if the number of nodes in each block of the acyclic aggregation is small enough compared with the number of nodes in the entire Boolean network. PMID- 26259250 TI - Tivantinib (ARQ 197) affects the apoptotic and proliferative machinery downstream of c-MET: role of Mcl-1, Bcl-xl and Cyclin B1. AB - Tivantinib, a c-MET inhibitor, is investigated as a second-line treatment of HCC. It was shown that c-MET overexpression predicts its efficacy. Therefore, a phase 3 trial of tivantinib has been initiated to recruit "c-MET-high" patients only. However, recent evidence indicates that the anticancer activity of tivantinib is not due to c-MET inhibition, suggesting that c-MET is a predictor of response to this compound rather than its actual target. By assessing the mechanisms underlying the anticancer properties of tivantinib we showed that this agent causes apoptosis and cell cycle arrest by inhibiting the anti-apoptotic molecules Mcl-1 and Bcl-xl, and by increasing Cyclin B1 expression regardless of c-MET status. However, we found that tivantinib might antagonize the antiapoptotic effects of c-MET activation since HGF enhanced the expression of Mcl-1 and Bcl xl. In summary, we show that the activity of tivantinib is independent of c-MET and describe Mcl-1, Bcl-xl and Cyclin B1 as effectors of its antineoplastic effects in HCC cells. We suggest that the predictive effect of c-MET expression in part reflects the c-MET-driven overexpression of Mcl-1 and Bcl-xl in c-MET high patients and that these molecules are considered as possible response predictors. PMID- 26259251 TI - beta-catenin stabilization enhances SS18-SSX2-driven synovial sarcomagenesis and blocks the mesenchymal to epithelial transition. AB - beta-catenin is a master regulator in the cellular biology of development and neoplasia. Its dysregulation is implicated as a driver of colorectal carcinogenesis and the epithelial-mesenchymal transition in other cancers. Nuclear beta-catenin staining is a poor prognostic sign in synovial sarcoma, the most common soft-tissue sarcoma in adolescents and young adults. We show through genetic experiments in a mouse model that expression of a stabilized form of beta catenin greatly enhances synovial sarcomagenesis. Stabilization of beta-catenin enables a stem-cell phenotype in synovial sarcoma cells, specifically blocking epithelial differentiation and driving invasion. beta-catenin achieves its reprogramming in part by upregulating transcription of TCF/LEF target genes. Even though synovial sarcoma is primarily a mesenchymal neoplasm, its progression towards a more aggressive and invasive phenotype parallels the epithelial mesenchymal transition observed in epithelial cancers, where beta-catenin's transcriptional contribution includes blocking epithelial differentiation. PMID- 26259253 TI - Fuzzy Petri nets Using Intuitionistic Fuzzy Sets and Ordered Weighted Averaging Operators. AB - Fuzzy Petri nets (FPNs) are an important modeling tool for knowledge representation and reasoning, which have been extensively used in a lot of fields. However, the conventional FPN models have been criticized as having many shortcomings in the literature. Many different models have been suggested to enhance the performance of FPNs, but deficiencies still exist in these models. First, various types of uncertain knowledge information provided by domain experts are very hard to be modeled by the existing FPN models. Second, the traditional FPNs determine the results of knowledge reasoning using the min, max, and product operators, which may not work well in many practical applications. In this paper, we propose a new type of FPN model based on intuitionistic fuzzy sets and ordered weighted averaging operators to deal with the problems and improve the effectiveness of the conventional FPNs. Moreover, a max-algebra-based reasoning algorithm is developed in order to implement the intuitionistic fuzzy reasoning formally and automatically. Finally, a case study concerning fault diagnosis of aircraft generator is presented to demonstrate the proposed intuitionistic FPN model. Numerical experiments show that the new FPN model is feasible and quite effective for knowledge representation and reasoning of intuitionistic fuzzy expert systems. PMID- 26259254 TI - An Efficient Leave-One-Out Cross-Validation-Based Extreme Learning Machine (ELOO ELM) With Minimal User Intervention. AB - It is well known that the architecture of the extreme learning machine (ELM) significantly affects its performance and how to determine a suitable set of hidden neurons is recognized as a key issue to some extent. The leave-one-out cross-validation (LOO-CV) is usually used to select a model with good generalization performance among potential candidates. The primary reason for using the LOO-CV is that it is unbiased and reliable as long as similar distribution exists in the training and testing data. However, the LOO-CV has rarely been implemented in practice because of its notorious slow execution speed. In this paper, an efficient LOO-CV formula and an efficient LOO-CV-based ELM (ELOO-ELM) algorithm are proposed. The proposed ELOO-ELM algorithm can achieve fast learning speed similar to the original ELM without compromising the reliability feature of the LOO-CV. Furthermore, minimal user intervention is required for the ELOO-ELM, thus it can be easily adopted by nonexperts and implemented in automation processes. Experimentation studies on benchmark datasets demonstrate that the proposed ELOO-ELM algorithm can achieve good generalization with limited user intervention while retaining the efficiency feature. PMID- 26259252 TI - miRNA-99b-5p suppresses liver metastasis of colorectal cancer by down-regulating mTOR. AB - Liver metastasis is common in patients diagnosed with colorectal cancer (CRC), and is also correlated with poor outcome. In this study we screened the different expression profiles of microRNAs (miRNAs) on the development of liver metastasis in CRC patients. miR-99b-5p was found to be more than 6-fold higher in primary tumors than in matched liver metastases (P = 0.007). Expression of miR-99b-5p in primary tumors of patients with stage III CRC without liver metastases was higher than in CRC patients with liver metastases (P = 0.028). Up-regulated miR-99b-5p was associated with longer overall survival (P = 0.01). Besides, miR-99b-5p silencing in miR-99b-5p-positive CRC cell lines promoted cell migration and up regulated mTOR, and vice versa. In addition, luciferase assays demonstrated that miR-99b-5p functioned as a tumor suppressor by targeting mTOR. Taken together, our results demonstrate thatmiR-99b-5p is differently expressed in primary CRC and liver metastasis and functions as a tumor-suppressive microRNA in metastatic CRC. The miR-99b-5p-mTOR axis may serve as a prognostic factor and therapeutic target for anti-metastatic therapy in CRC patients. PMID- 26259255 TI - [Effect of lumbar (perirenal) procaine blockade on microcirculation and exchange proteoglycans with experimental gonarthrosis]. AB - Experimental studies on guinea pigs of both sexes (n = 30). Experimental animals are awicea into equal groups oJ 10 animals: 1--the control group (intact animals), 2--the comparison group (modelling of gonarthrosis by crossing his own patellar ligament has been made, exposure 6 months), 3--the main group (animals with gonarthrosis treatment was carried out by performing lumbar procaine blockade (LPB) with an interval of 3-5 days three times). We establish that after a course of LPB in gonarthrosis marked increase in the density of the injected channel in the articular and periarticular structures, which reflects a growth in the microcirculation, and more intense accumulation in the basic substance of epiphyseal cartilage PAS (+) indicates the material to increase the level of proteoglycan in articular cartilage. PMID- 26259256 TI - Jure Piskur (1960 - 2014). PMID- 26259257 TI - Implementing the Affordable Care Act: Revisiting the ACA's Essential Health Benefits Requirements. AB - The Affordable Care Act broadens and strengthens the health insurance benefits available to consumers by requiring insurers to provide coverage of a minimum set of medical services known as "essential health benefits." Federal officials implemented this reform using transitional policies that left many important decisions to the states, while pledging to reassess that approach in time for the 2016 coverage year. This issue brief examines how states have exercised their options under the initial federal essential health benefits framework. We find significant variation in how states have developed their essential health benefits packages, including their approaches to benefit substitution and coverage of habilitative services. Federal regulators should use insurance company data describing enrollees' experiences with their coverage--information called for under the law's delayed transparency requirements--to determine whether states' differing strategies are producing the coverage improvements promised by reform. PMID- 26259258 TI - Implementing the Affordable Care Act: State Action to Establish SHOP Marketplaces. AB - The Affordable Care Act seeks to help small employers offer coverage by reforming the small-group market and establishing Small Business Health Options Program (SHOP) marketplaces. Seventeen states and the District of Columbia chose to operate their own SHOP marketplaces in 2014, with the federal government operating the SHOP marketplace in 33 states. This brief examines state decisions to enhance the value of SHOP marketplaces for small employers and finds that most have set predictable participation and eligibility requirements and will offer a competitive choice of insurers and plans. States also are seeking to facilitate small employers' shopping experience through online tools and access to personalized assistance. While not all SHOP marketplaces are yet functioning as intended, their establishment offers an opportunity to identify successful strategies for improving the affordability and accessibility of coverage for small employers. PMID- 26259259 TI - Managing Skin Tears With MEDIHONEY(r). PMID- 26259260 TI - Proactive, Not Reactive. PMID- 26259261 TI - Patient communication: ensuring compliance with governments regulations. PMID- 26259262 TI - Why ergonomics should be emphasized in dental school curricula. PMID- 26259263 TI - [ISOLATION OF ANTIBIOTICS RESISTANCE GENES IN VIBRIO CHOLERAE O1 AND O139 SEROGROUP STRAINS]. AB - AIM: Determination of sensitivity of V. cholerae O1 serogroup El Tor biovar and O139 serogroup strains to antibiotics and determination of the presence of antibiotics resistance genes in their genome. MATERIALS AND METHODS: The studies were carried out in 75 V. cholerae O1 and O139 serogroup strains. Sensitivity of cultures to antibiotics was determined by disc-diffusion method. DNA isolation was carried out in the presence of 6M guanidine thiocyanate. PCR was carried out in multi-channel amplificator Tercyc. RESULTS: A multiplex PCR was constructed, that includes 5 primer pairs for the detection of O1 and O139 serogroup resistance genes of vibrios to sulfame- thoxazolum, streptomycin B, trimethoprim, the presence of SXT element, an amplification program was developed. Using the developed PCR, V. cholerae O1 serogroup El Tor biovar strains with multiple drug resistance were established to be imported into Russia in 1993. The presence of SXT elements with genes of resistance to 4 antibiotics simultaneously was detected precisely in these strains, that belong to toxigenic genovariants of V. cholerae El Tor biovar. All the El Tor vibrio strains imported in the subsequent years were shown to stably preserve SXT element, this indicates its important role in biology of cholera vibrios. O139 serogroup strains with intact SXT element and having a deletion of the gene coding trimethoprim resistance were isolated. CONCLUSION: The data obtained may be used to establish molecular genetic mechanisms of emergence of antibiotics resistant strains of cholera vibrio, construction of novel gene diagnostic test-systems and carrying out passportization of strains that are stored in the State collection of pathogenic bacteria. PMID- 26259264 TI - [EVALUATION OF FUNCTIONAL FEATURES AND STRESS RESISTANCE OF ISOGENIC TOXIGENIC AND NON-TOXIGENIC BIOVAR EL TOR VIBRIO CHOLERAE STRAINS]. AB - AIM: Comparative evaluation of functional features of toxigenic biovar El Tor Vibrio cholerae strains and their spontaneous non-toxigenic mutants and study of their resistance to saline and oxidative stress. MATERIALS AND METHODS: 8 biovar El Tor V. cholerae strains were studied: 4 clinical strains isolated in 1970 from patients in Astrakhan and 4 spontaneous non-toxigenic mutants of these strains that have lost cholera toxin genes as a result of residence in river water at the temperature of 25 degrees C. Protein composition was determined in polyacrylamide gel electrophoresis by Laemmli U.K. Stress resistance of the strains was studied by adding H2O2 to 20 mM concentration and NaCl to 3 mM concentration to the cultural suspension. RESULTS: Loss of cholera toxin genes was shown to be accompanied by changes in the level of expression of 17 proteins including those that take part in energy metabolism, glucose transport, chemotaxis and purine bases. Moreover, non-toxigenic strains were established to be 5-15 times more resistant to saline and oxidative stress compared with toxigenic strains. CONCLUSION: Non-toxigenic V. cholerae mutants adopt better to stress factors, therefore the loss of cholera toxin gene in water environment could be one of the methods of adaptation of pathogenic bacteria to changes in the environment. PMID- 26259265 TI - [EXPERIENCE OF USING IMMUNE CHROMATOGRAPHY TEST FOR DIAGNOSTICS OF PNEUMOCOCCAL PNEUMONIA]. AB - AIM: Justification of the use of immune chromatographic analysis for diagnostic of pneumococcal pneumonia. MATERIALS AND METHODS: Sensitivity and specificity of an immune chromatographic method (Binax Now test system) was studied for verification of pneumococcal pneumonia. Approbation of this method for etiologic deciphering of pneumonia in 260 patients hospitalized in infectious hospital was carried out. RESULTS: A high sensitivity (84.8%) and specificity (90.5%) of the chromatography test was established. Streptococcus pneumoniae antigen in urine of patients with community acquired pneumonia was determined 3.6 times more frequently when immune chromatographic test was used compared with bacteriological study of nasopharyngeal swab and 1.8 times more frequently compared with sputum bacteriological study. CONCLUSION: Application of immune chromatographic express test Binax Now could be recommended for timely verification of pneumococcal pneumonia along with bacteriological methods of study. PMID- 26259266 TI - [POSSIBILITY OF USING NESTED POLYMERASE CHAIN REACTION FOR DIAGNOS- TICS OF DISEASES CAUSED BY VARICELLA ZOSTER VIRUS]. AB - AIM: Demonstrate the possibility of using nested PCR method for determination of Varicella Zoster virus (VZV) in clinical samples of peripheral blood of patients. MATERIALS AND METHODS: Material from 35 patients with clinical manifestations of herpes zoster and control group of 20 healthy donors was used in the study. Monocyte fraction of venous blood cells, pretreated with heparin, was isolated by centrifugation in ficoll-verografin density gradient, total DNA was then isolated from cells by phenol-chloroform extraction with subsequent precipitation with alcohol. Polymerase chain reaction was carried out in thermocyclers Tercyc and TProfessional Gradient (Biometra), amplified DNA was analyzed by electrophoresis on 1.6% agarose gel in the presence of ethidium bromide. RESULTS: Data on detection of viral DNA in blood monocytes in 17 (49%) of ill patients, as well as in 1 (out of 20 in control group) practically healthy donor were obtained. A possibility of a subclinical reactivation of the virus is discussed in the latter case. CONCLUSION: A possibility of viral DNA determination in monocytes of patient blood without using expensive equipment is shown, that could find application in clinical practice, especially for diagnostics of patients with non characteristic clinical manifestations, as well as patients with subclinical forms of the disease. PMID- 26259267 TI - [EFFECTIVENESS OF POLYCATIONIC NANOPARTICLES OF POLYETHYLENEIMINE-POLYHYDROZIDE CHITOSAN (PEI-PG-OCHG) AS A VECTOR FOR SMALL INTER- FERING RNA, DIRECTED TO SUPPRESS HERPES SIMPLEX TYPE 2 VIRUS REPLICATION]. AB - AIM: Evaluation of an antiviral effect of miRNA in the nanoparticles of a polycationic compound against mRNA of vp16 protein (UL48 gene) of herpes simplex virus type 2 (HSV-2) in vitro. MATERIALS AND METHODS. 50% aqueous solution of polyethyleneimine (BDH, Great Britain), chitosan, containing approximately 15% of N-acetylated glucosamine chains (Sonat, Russia), hydrazine-hydrate and other chemical reagents (Chimmed, Russia); Vero continuous cell line, MS HSV-2 virus were used. Vero cells were cultivated in DMEM medium supplemented by 10% fetal bovine serum at 37 degrees C in the atmosphere of 5% CO2. Cell viability was evaluated by using Neutral Red vital stain and MTT-test. Primers and probes for RT-PCR were modeled in Vector NTI 8.0 computer program according to the mRNA sequences of the studied genes (the sequences were obtained from GenBank) and synthesized in Sintol (Russia). RT-PCR tests were set using a standard procedure. Synthesis of PEI-PG-chitosan was carried out by Krivtsov G.G. et al. (2010). RESULTS: A design and synthesis of nucleotide sequences, that have interfering activity against this virus, was carried out to study the effect of siRNA on HSV 2 virus replication. During simultaneous addition of HSV-2 and specific siRNA to Vero cells in cell culture, a significant (by 4 lg) reduction of virus yield was observed. A level of UL48 mRNA expression level was determined after the influence of various siRNA variants. A S2 siRNA variant was shown to cause the most pronounced virus-inhibiting effect, aiming for the center of RNA-target (the level of expression of the studied gene decreased by 0.5 lg). CONCLUSION: siRNA in the PEI-PG-chitosan complexes were established to possess in vitro pronounced suppressive HSV-2 replication activity. The results obtained could be used in creation of new therapeutic preparation against herpes viruses. PMID- 26259268 TI - [COMPARATIVE STUDY OF IMMUNOGENICITY AND PROTECTIVE EFFECT OF LIVE COLD-ADAPTED AND INACTIVATED VACCINES AGAINST TYPE A INFLUENZA]. AB - AIM: Direct comparative studies of immunogenicity and protective effect of live cold-adapted (ca) and inactivated vaccines against type A influenza. MATERIALS AND METHODS: Groups of mice were immunized intramuscularly (i/m) or intranasally (i/n) twice with inactivated or live ca vaccines based on wild-type parent strain A/Krasnodar/101/59 (H2N2) and the corresponding ca donor strain A/Krasnodar/101/59/30CE/5MDCK/l/7/4 (H2N2), respectively. Immunogenicity was determined by HAI antibodies in sera and lungs (extracts) against both vaccine strains. Protective effect--by the level of wild-type strain in lungs of immunized mice after the infection. RESULTS: Live ca and inactivated vaccines based on similar strains increase immunogenicity and protective effect when administered via different routes in varying patterns. A significant increase of immunogenicity was only observed for i/m (sera antibodies) and i/n (lung antibodies) administration of the live ca vaccine, and could be determined by antigenic features of the vaccine strains. At the same time, all the vaccine variants and administration routes induced at least partial protection from infection compared with unimmunized control. However, complete protection from infection was only noted for the i/m administered live ca vaccine. CONCLUSION: A combination of immunization variant and vaccine type determines immunogenicity and protective effect, and their interconnection requires further studies using all the possible combinations of preparations and administration routes as well as determination of induction of various components of the immune system. PMID- 26259269 TI - [EPITOPIC SPECIFICITY OF A SYNTHETIC DISACCHARIDE, RECURRING LINK OF CAPSULE POLYSACCHARIDE CHAIN OF SEROTYPE 3 STREPTOCCUS PNEUMONIAE]. AB - AIM: Study epitopic specificity of synthetic disaccharide, recurring link of serotype 3 S. pneumoniae, conjugated with bovine serum albumin (BSA). MATERIALS AND METHODS: Conjugate of the synthetic disaccharide with BSA was obtained by squarate method. Antigenic activity of the conjugate was studied in competitive EIA. Titers of IgG against capsule polysaccharide of serotype 3 S. pneumoniae were determined in EIA by using sera of mice immunized twice with disaccharide conjugate sorbed onto aluminum hydroxide. RESULTS: Disaccharide conjugate used as a well-covering antigen (4 ug/well) in EIA was characterized by a high degree of specificity and interacted only with IgG against serotype 3 S. pneumoniae in antimicrobial sera of animals without reacting with antibodies (ABs) against other pneumococcus serotypes (6B, 10A, 19A, 19F, 23F). Disaccharide conjugated with BSA was determined in competitive EIA to inhibit bonding of ABs to disaccharide by 78.8%, bacterial capsule polysaccharide by 56.9%, BSA did not inhibit the sera activity. The study of sera of mice immunized by serotype 3 S. pneumoniae disaccharide conjugate in EIA, where capsule polysaccharide was used as a plate-sorbed antigen, has established the presence of IgG against capsule polysaccharide at a titer of 1:1600. CONCLUSION: The disaccharide that is a single recurring link of serotype 3 S. pneumoniae contains a key epitope of capsule polysaccharide. The synthetic disaccharide could be used as a component of multivalent conjugated pneumococcal vaccines and for development of diagnostic test-systems. PMID- 26259270 TI - [INTESTINE MICROBIOTA IN CHILDREN WITH OBESITY AND ALLERGIC DISEASES]. AB - AIM: Study intestine microflora in children with obesity and evaluate its association with allergic diseases. MATERIALS AND METHODS. 66 children with various body weight aged 3 to 17 years were included into the study. Intestine microflora study in children was carried out according to the order of the Ministry of Health of Russian Federation No. 231 of 09.06.2003 "Regarding approval of sectoral standard "Patient management protocol. Intestine dysbacteriosis" (SST 91500.11.0004-2003). RESULTS: In healthy children depending on body weight an increase of the number of Firmicutes type microorganisms and a decrease of the number of microbes, belonging to Bacteroidetes type, was detected. The presence of allergic pathology was accompanied by a decrease of the number of Bacteroidetes and the presence of Bacillus and Staphylococcus aureus regardless of the body weight. At the same time, in all the children an increase of the content of Clostridium with the increase of body mass was noted. CONCLUSION. The data obtained have revealed an association of changes in intestine microbiota with the development of obesity and allergopathology. PMID- 26259271 TI - [REAL TIME POLYMERASE CHAIN REACTION IN TULAREMIA LABORATORY DIAGNOSTICS]. AB - AIM: Enhancement of tularemia laboratory diagnostics by F. tularensis DNA determination in blood sera of patients using real time polymerase chain reaction (RT-PCR). MATERIALS AND METHODS: 39 blood sera of patients obtained during transmissive epidemic outbreak of tularemia in Khanty-Mansiysk in 2013 were studied in agglutination reaction, passive hemagglutination, RT-PCR. Specific primers and fluorescent probes were used: ISFTu2F/R+ISFTu2P, Tu14GF/R+tul4-PR2. RESULTS: Advantages of using RT-PCR for early diagnostics of tularemia, when specific antibodies are not detected using traditional immunologic methods, were established. Use of a combination of primers and ISFTu2F/R+ISFTu2P probe allowed to detect F. tularensis DNA in 100% of sera, whereas Tul4G F/R+tul4-PR2 combination--92% of sera. The data were obtained when DNA was isolated from sera using "Proba Rapid" express method. Clinical-epidemiologic diagnosis oftularemia was confirmed by both immune-serologic and RT-PCR methods when sera were studied 3-4 weeks after the onset of the disease. CONCLUSION: RT-PCR with ISFTu2F/R primers and fluorescent probe ISFTu2P, having high sensitivity and specificity, allows to determine F. tularensis DNA in blood sera of patients at both the early stage and 3-4 weeks after the onset of the disease. PMID- 26259272 TI - [DETERMINATION OF CRITICAL CONCENTRATION OF CHEMOTHERAPY DRUGS FOR MYCOBACTERIUM TUBERCULOSIS SENSITIVITY EVALUATION USING Sensititre MyCoTB TEST SYSTEM]. AB - AIM: Determination of critical concentration for chemotherapy drugs, widely used for tuberculosis treatment, for use in Mycobacterium tuberculosis drug sensitivity results evaluation by Sensititre MycoTB test-system. MATERIALS AND METHODS: Minimal inhibiting concentration (MIC) of isoniazid, rifampicin, streptomycin, ethambutol, amikacin, kanamycin, ofloxacin and moxifloxacin against conditionally sensitive and conditionally resistant strains of tuberculosis mycobacteria (TBM), isolated from various diagnostic material, obtained from patients with various forms of lung tuberculosis being treated in MCSPCTC hospital and dispensaries for tuberculosis control of Moscow, were studied in Sensititre MycoTB test system. RESULTS: Critical concentration of chemotherapy drugs for MycoTB test system was determined as a result of the obtained MIC values analysis as the minimal concentration that suppressed growth of 95% of sensitive strains and does not obstruct growth of 95% of resistant. The following MIC values were established: streptomycin--1.0, isoniazid--0.25, rifampicin--1.0, ethambutol--4.0, ofloxacin--2.0, moxifloxacin--0.25, kanamycin--2.5 and amikacin- 1.0 ug/ml. CONCLUSION: The developed critical concentration of the mentioned preparations is currently used for evaluation of sensitivity/ resistance of TBM clinical isolates from MCSPCTC. PMID- 26259273 TI - [CRITERIA OF DIFFERENCE EVALUATION FOR VARIOUS TYPES OF HEMORRHAGIC FEVER WITH RENAL SYNDROME FOCI. HFRS FOCI IN VARIOUS BIOTOPES OF TYPICAL BARRENS]. AB - AIM: Examine features of natural, natural-anthropourgic and anthropourgic foci of hemorrhagic fever with renal syndrome (HFRS) in various, mostly forest, biotopes of typical barrens due to differences of non-specific HFRS prophylaxis in foci of various types. MATERIALS AND METHODS: Epizootological and epidemiologic data from 1998 to 2012 were analyzed, gathered in HFRS foci of all types in Saratov area of Saratov Region (typical barrens). 14,606 trap-nights were worked off and 2669 small mammals were procured. The most significant population-ecologic and ecologic-epizootological methods and criteria were used for comparative analysis of differences for 3 types of foci. RESULTS: Based on analysis of multi-year data seasonal differences for HFRS foci of various types were shown by 10 population ecologic and ecologic-epizootologic criteria. CONCLUSION: The results obtained allow to state that modern means and methods of non-specific prophylaxis of HFRS and other zoonoses in foci of various types different significantly. This allows the most rational use of material and financial resources. PMID- 26259274 TI - [CHARACTERISTICS OF FORMATION, INHIBITION AND DESTRUCTION OF YERSINIA PSEUDOTUBERCULOSIS BIOFILMS FORMING ON ABIOTIC SURFACES]. AB - AIM: Detection of conditions of Yersinia pseudotuberculosis biofilm formation, their quantitative testing. MATERIALS AND METHODS: Y. pseudotuberculosis strains, nutrient media, standard 96-well polystyrene plates, crystal violet dye as well as bacteriologic, spectrophotometric, statistical methods were used. RESULTS: All the studied Y pseudotuberculosis strains formed a well expressed biofilm on abiotic surface during cultivation of bacteria in 200 ul of a plate well at a temperature of 20-22 degrees C for 4-7 days. Bacteria CFU number in biofilm reduced by day 10 of incubation. DNAse I was found to inhibit biofilm formation, and also partially destroyed mature Y. pseudotuberculosis biofilm. The presence of DNA in extra-cellular matrix of biofilm was shown. CONCLUSION: An ability of Y. pseudotuberculosis to form biofilm on abiotic surface was established. The conditions of biofilm formation were determined. Inhibiting effect of DNAse I on Y. pseudotuberculosis was shown. PMID- 26259275 TI - [EFFECTIVENESS OF PREVENTIVE VACCINE PROPHYLAXIS OF CHICKEN POX IN MILITARY COLLECTIVES]. AB - AIM: Study the effectiveness of preventive vaccine prophylaxis of chicken pox in military collectives. MATERIALS AND METHODS: In the focus of chicken pox, 200 servicemen of the new addition by conscription were immunized once against chicken pox; 97 servicemen by conscription of the new addition (comparison group) were not vaccinated. Epidemiologic and immunologic effectiveness of conduction of preventive vaccine prophylaxis in chicken pox focus were studied. RESULTS: In the group of 200 soldiers, that were present in the focus of infection and were immunized once against chicken pox, only 2 cases of this disease were registered (10 per thousand). In the comparison group, that consisted of 97 unvaccinated servicemen, chicken pox disease was registered in 7 individuals (72 per thousand). Epidemiologic effectiveness of preventive vaccine prophylaxis of chicken pox amounted to 86%. Immunologic effectiveness of vaccination 2-3 weeks after the immunization was 42%, and 2 months after--44%. Local reactions in the form of hyperemia (up to 1.5 cm) and edema were noted in 10% of the vaccinated at the location of preparation administration; in 1.7%--general reaction in the form of temperature increase to 37.8 degrees C was observed. Post-vaccinal complications in the immunized group were not detected. CONCLUSION: Preventive vaccination of servicemen allows to minimize the spread of chicken pox, however can not serve as means of complete elimination of the infection from military collectives. PMID- 26259276 TI - [PROTEOMIC MASS-SPECTROMETRIC ANALYSIS OF FRESHLY ISOLATED ESCHERICHIA COLI STRAINS]. AB - AIM: Time-of-flight mass-spectrometric analysis of colon bacilli populations freshly isolated from humans for identification of proteome markers, that are characteristic for hemolytic and non-hemolytic strains, E.coli--associants of opportunistic bacteria. MATERIALS AND METHODS: 20 strains of monopopulation of hemolytic E.coli; 100 strains of monopopulation of non-hemolytic E. coli; 15 non hemolytic strain, isolated from association with opportunistic bacteria. Protein profiling on MALDI-TOF MS Autoflex "Bruker Daltonik" mass-spectrometer. RESULTS: Value within species for mass-charge peak with 100% intensity of 9000 Da could be a differential sign for isolation of hemolytic E.coli during mass-spectrometric biotyping. CONCLUSION: Proteomic characteristics of strains from various populations within E.coli are given. Taxon-specific markers for proteomic differentiation of E.coli populations are established. PMID- 26259278 TI - [ORNITHOSIS OUTBREAKS AMONG POPULATION OF ORENBURG AND KURGAN RE- GIONS IN 2008 2009]. AB - There have been presented analysis of ornithosis outbreaks among population of Orenburg and Kurgan regions in 2008-2009. Find out factors and conditions that promote conducive of epidemic foci. Have been presented a list of the main preventive measures. PMID- 26259277 TI - [ANTIMICROBIAL ACTIVITY OF POLYAZOLIDINAMMONIUM, MODIFIED WITH HYDRATE-IONS OF IODINE]. AB - AIM: Study of antimicrobial activity of a polymer compound--polyazolidinammonium, modified with hydrate-ions of iodine. MATERIALS AND METHODS: Antimicrobial activity of polyazolidinammonium, modified with hydrate-ions of iodine, against reference strains and clinical isolates of Gram positive and negative bacteria, microscopical fungi, as well as RNA viruses was studied. RESULTS: High antibacterial activity of the studied compound was established, especially against Gram positive bacteria. A higher concentration of the preparation (125 250 ug/ml) was characterized by anti-fungal effect. A high sensitivity to polymer of swine transmissible gastroenteritis virus was noted. CONCLUSION: The polymer compound, based on the results of the studies, is a perspective antiseptic and etiotropic means for control of infectious disease causative agents. PMID- 26259279 TI - [CONTEMPORARY CONCEPTION OF IMMUNE RESPONSE ACTIVATION MECHA- NISM BY CONJUGATED POLYSACCHARIDE VACCINES]. AB - Vaccination remains the most effective method of control of spread of a whole range of infections of both viral and bacterial nature. Many bacterial pathogens (Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae) carry polysaccharide capsule on the surface, that is one of the elements of protection from host organism immune system. At the same time, vaccination with bacteria exopolysaccharides (EPS) ensures infection neutralization. Effectiveness of such vaccine prophylaxis is limited by age of the vaccinated, intensity and duration of the immunity, development of secondary immune response. EPS conjugation with protein antigens was known for a long time to ensure activation of T-cell immunity against EPS and formation of secondary immune response. However, detailed studies of mechanism of immunity modulation by a protein partner as part of a glycoconjugate has not been carried out. T-lymphocyte activation was traditionally thought to occur exclusively due to peptide presentation, that are products of processing of protein component of the conjugate. Recently, information, accumulated in the field of natural carbohydrate, glycolipid and glycoprotein antigen presentation to T-cells, has generated interest in studying mechanisms of cell immunity activation by conjugated vaccines. Progress in this field, as well as development of novel chemical and biochemical, including combinative technologies of synthesis and study of these molecules, opens new opportunities for detailed understanding of mechanism of action for conjugated vaccines and creation of glycoconjugates with increased effectiveness of protective action. PMID- 26259280 TI - [VARICELLA ZOSTER VIRUS AND DISEASES OF CENTRAL NERVOUS SYSTEM VESSELS]. AB - Systemized data on epidemiology, pathogenesis, clinical manifestation, diagnostics and therapy of VZV-vasculopathy--a disease, occurring due to damage of arteries of the central nervous system by Varicella Zoster virus, are presented in the review. A special attention in the paper is given to the effect of vaccine prophylaxis of chicken pox and herpes zoster on the frequency of development and course of VZV-vasculopathy. PMID- 26259281 TI - [CONTEMPORARY TENDENCIES IN CONSTRUCTING RECOMBINANT VACCINES FOR SPECIFIC PROPHYLAXIS OF PLAGUE]. AB - An importance place in the system of prophylaxis measures against plague is allotted to vaccination of population contingents, that belong to risk groups for infection. The whole arsenal of accumulated knowledge on structure, properties, molecular nature, genetic determination, synthesis pathways, regulation and mechanisms of interaction with macroorganism of pathogenicity factors and immunogenicity of the infectious disease causative agent is used in the creation of new generation of vaccines. Contemporary technologies--genomics, proteomics, reverse vaccinology facilitate detection of protective antigens and help determine rational design of the vaccines. Main tendencies in development of recombinant live and chemical vaccines for specific prophylaxis of plague are presented in the review. Constructive approaches, that allow to produce highly effective and safe preparations are isolated. PMID- 26259282 TI - [Orientation of the immune response of the epithelium: epithelial cells, dendritic cells and lymphocytes]. PMID- 26259283 TI - [Psoriasis: how the epithelium influences the immune response: keratinocytes, dendritic cells and T lymphocytes]. AB - Psoriasis is an autoinflammatory skin disease mediated by interactions between keratinocytes, dendritic cells and T lymphocytes, which create a vicious circle of cell activation and lead to the development and persistence of skin lesions. Inflammatory cytokines produced by these three cell types, especially TNFalpha, IL-23 and IL-17, are central to the disease and are the targets of new, highly effective immunobiological therapies. Advances in the pathophysiology and treatment of psoriasis have applications far beyond the skin disease itself Indeed, psoriasis serves as a model for studies of the mechanisms of chronic inflammation such as rheumatoid arthritis, Crohn's disease, atherosclerosis and type 2 diabetes, and for developing new targeted therapies for autoinflammatory diseases. PMID- 26259284 TI - [Cross-talk between differentiated cells in different tissues: the example of asthma]. AB - Asthma is a chronic inflammatory airway disorder that leads to symptoms such as coughing, wheezing and chest tightness. Typical features of asthma are chronic airway inflammation and remodeling, leading to airway obstruction. The airway epithelium is considered as an essential controller of inflammatory, immunological and regenerative responses to allergens. Abnormal molecular crosstalk between bronchial epithelial and immune cells plays an important role in driving chronic inflammation and airway remodeling. Drugs that selectively inhibit crucial aspects of epithelial-immune or epithelial-mesenchymal interactions could potentially prevent these processes. PMID- 26259285 TI - [Biopersistence and systemic distribution of intramuscularly injected particles: what impact on long-term tolerability of alum adjuvants?]. AB - Aluminium oxyhydroxide (alum), a nanocrystalline compound that forms agglomerates, has been widely used as a vaccine adjuvant since 1927, but the mechanisms by which it stimulates immune responses remain poorly understood. Although generally well tolerated, alum may occasionally cause chronic health problems in presumably susceptible individuals. Some individuals may rarely develop delayed-onset diffuse myalgia, chronic exhaustion and cognitive dysfunction, associated with long-term persistence (up to 12 years) of alum loaded macrophages at site of i.m. immunization, defining so-called macrophagic myofasciitis (MMF). Symptoms are consistent with the chronic fatigue/myalgic encephalomyelitis (CFS/ME) syndrome, and have been used as a paradigm of the "autoimmune/inflammatory syndrome induced by adjuvants" (ASIA). Cognitive dysfunction is reminiscent of that described in workers exposed to inhaled Al particles. Individual susceptibility may influence both alum biopersistence and difusion away from injection sites. Biopersistent particles such as fluorescent alum-coated nanohybrids, when injected into mouse muscle, are captured by monocyte-lineage cells and then carried to distant organs, draining lymph nodes and blood, probably via the thoracic duct, with delayed and accumulative translocation to the brain (microglial cells). Brain penetration occurs at extremely low levels in normal conditions, possibly explaining the good tolerance of alum despite its high neurotoxic potential. However, systemic diffusion is considerably enhanced by the potentiating effect of MCP-1, the main monocyte chemoattractant factor, the production of which is subject to marked variations linked to age and to genetic and environmental factors. Selective MCP-1 elevation is the only known circulating biomarker of MMF. PMID- 26259286 TI - [Masked hypertension]. AB - "Masked hypertension" is defined as high blood pressure outside the medical setting (ambulatory or self-measurement at home) and normal BP in the medical setting Masked hypertension is frequent, particularly in patients receiving antihypertensive treatment. It is often associated with other cardiovascular risk factors. The cardiovascular prognosis in terms of target organ damage and complications is poorer than that of subjects considered normotensive by all measurement methods, and similar to that of subjects considered hypertensive by all measurement methods. Its pathophysiological mechanism is unknown. No controlled trials have yet been conducted to determine the possible benefits of treatment. PMID- 26259287 TI - [Obesity and the prognosis of heart failure: the obesity paradox, myth or reality?]. AB - Obesity has now reached epidemic proportions worldwide. Obesity is associated with numerous comorbidities, including hypertension, lipid disorders and type II diabetes, and is also a major cause of cardiovascular disease, coronary disease, heart failure, atrial fibrillation, and sudden death. Obesity is the main cause of heart failure in respectively 11% and 14% of cases in men and women. The Framingham study showed that, after correction for other risk factors, each point increase in the body mass index raises the risk of heart failure by 5% in men and 7% in women. Obesity increases the heart workload, causes left ventricular hypertrophy, and impairs both diastolic and systolic function. The most common form of heart failure is diastolic dysfunction, and heart failure in obese individuals is associated with preserved systolic function. Despite these comorbidities and the severity of heart failure, numerous studies have revealed an "obesity paradox" in which overweight and obese individuals with heart failure appear to have a better prognosis than non overweight subjects. This review summarizes the adverse cardiac effects of this nutritional disease, the results of some studies supporting the obesity paradox, the better survival rate of obese patients with heart failure. Potential explanations for these surprising data include the possibility that a number of obese patients may simply not have heart failure, as well as methodological bias, and protective effects of adipose tissue. Further studies of large populations are needed to determine how obesity may improve the prognosis of heart failure. PMID- 26259288 TI - [Stem cell therapy and heart failure: hopes and disappointments]. AB - Despite therapeutic advances, heart failure remains a common and serious event characterized by initial and progressive loss of cardiac myocytes, a loss that is currently untreatable. Cell therapy has emerged as a promising new approach to the treatment of heart failure, with very encouraging experimental results. Since 2000, when human stem cell therapy was first attempted in France, clinical trials with adult stem cells (myoblasts, bone-marrow derived cells, mesenchymal stem cells) have given variable results. The inconsistent and modest therapeutic benefit observed in these studies is due more to paracrine effects than to the hoped-for cell replacement, as adult stem cells do not turn into cardiomyocytes and their survival rate after transplantation is very low. In order to be effective, cell therapy should use heart muscle cells derived from pluri- or multipotent cells (human embryonic stem cells, induced pluripotent stem cells, resident cardiac cells), which are likely to have a higher survival rate in a hostile biological environment and deteriorated tissue scaffold. Cardiac tissue engineering assisted by nanotechnologies may eventually help to meet this challenge. PMID- 26259289 TI - [Acute myocardial infarction in metropolitan France from 1995 to 2010: evolution of patient characteristics, management and outcomes]. AB - Cardiovascular disease is still one of the main causes of death in France, and acute myocardial infarction is one of its most severe complications. Data from four nationwide surveys conducted from 1995 to 2010 show that ST-elevation myocardial infarction (STEMI) has tended to affect younger subjects in recent years, while age of onset of non-ST-elevation myocardial infarction (NSTEMI) has remained relatively stable. Both the organization and the modalities of patient management have undergone profound modifications, with an increase in the use of invasive strategies and secondary medical prevention. Early mortality has fallen from 13.7% to 4.4% in STEMI patients, and from 10.9% to 3.0% in NSTEMI patients. PMID- 26259291 TI - [Ethical and legal aspects of telemedicine]. AB - The recent development of telemedicine, i.e. the use of communication technologies to transfer medical information, raises special ethical and legal issues. The HPST law regulates the delivery of remote healthcare in France. The ethical aspects of telemedicine are similar in many respects to those of conventional medicine, but the involvement of non clinical personnel and the use of technologies raise special issues such as confidentiality. Patients must be informed of these issues and their consent must be sought before employing telemedicine procedures. Finally, in case of malpractice complaints, the respective liabilities of the different disciplines involved in telemedicine must be determined PMID- 26259290 TI - [Genome sequencing and personalized medicine: perspectives and limitations]. AB - DNA sequencing technologies have advanced at an exponential rate in recent years: the first human genome was sequenced in 2001 after many years of effort by dozens of international laboratories at a cost of tens of millions of dollars, while in 2013 a genome can be sequenced within 24 hours for a few hundred dollars (exome sequencing takes only a few hours). More and more hospital laboratories are acquiring new high-throughput sequencing devices ("next-generation sequencers", NGS), allowing them to analyze tens or hundreds of genes, or even the entire exome. This is having a major impact on medical concepts and practices, especially with respect to genetics and oncology. This ability to search for mutations simultaneously in a large number of genes is finding applications in the diagnosis of Mendelian diseases (including at birth), routine screening for heterozygotes, and pre-conception diagnosis. NGS is now sufficiently sensitive to analyze circulating fetal DNA in maternal blood (cell-free fetal DNA, cffDNA), enabling applications such as non invasive diagnosis of fetal sex (and X-linked diseases), fetal rhesus among rhesus-negative women, trisomy and, in the near future, Mendelian mutations. Data on multifactorial diseases are still preliminary, but it should soon be possible to identify "strong" factors of genetic predisposition that have so far been beyond the scope of genome-wide association studies (GWAS). In the field of constitutional oncogenetics, NGS can also be used for simultaneous analysis of genes involved in " hereditary " cancers (21 breast cancer genes, 6 colon cancer genes, etc.). More generally, NGS can identify all genomic abnormalities (deletions, translocations, mutations) in a given malignant tissue (hemopathy or solid tumor), and has the potential to distinguish between important mutations (those that drive tumor progression) from " bystander " or accessory mutations, and also to identify "druggable" mutations amenable to targeted therapies (e.g. imatinib and Bcr/Abl rearrangement; verumafemib and the BRAF V600E mutation). Systematic sequencing of all the genes involved in drug metabolism and responsiveness will lead to individualized pharmacogenetics. Finally, sequencing of the tumoral and constitutional genomes, identfication of somatic mutations, and detection of pharmacogenetic variants will open up the era of personalized medicine. The first results of these targeted therapeutic indications show a gain in the duration of remission and survival, although the cost-effectiveness of these approaches remains to be determined. Finally, this huge capacity for genome sequencing raises a number of regulatory and ethical issues. PMID- 26259292 TI - [Informatics and health, from digitization to information and communication technologies (TIC)]. AB - Integrating the progress that has been made on a daily basis since it was jointly commissioned in 2013 by the French National Academy of Medicine (Biotechnology Committee XX, Prof Emmanuel-Alain Cabanis) and the Technologies Academy (Pr Jean de Kervasdoue), this report, covering such a vast subject, can only represent one step in a long process. Summarized here in a volume compatible with the Bulletin, it makes reference to the full report (52 pages ; 22 pages of text, 4 pages of references, a 20-page glossary for physicians, plus 522 figures spanning 6 pages), which is available on the Academy's website. The six chapters first define "health" (WHO) and "informatics" and provide a brief history. The first chapter, on technologies, is divided into "bad" news (cybercrime, ecological risks) and advances relevant to health. The next four chapters describe the contribution of digitization to patient management, ranging from "fragile" individuals (from the gamete to old age and dependency) to healthy subjects trained to work in hostile situations (scuba diving to space exploration), and finally research. The last chapter proposes 7 areas for progress: expansion of the national imaging and communications platforms, stimulation of the medical robotics industry, extension of telemedicine to all medical and surgical specialties, support for drug dispensing and therapeutic education, and foundation of a European portal for m-health certification, research prioritization according to multiyear health plans, and reinforcement of mathematic education, starting in primary school (see: "La main a la pate" ("Going hands-on"). PMID- 26259293 TI - [The National Academy of Medicine calls for postmortem brain donation for neurodegenerative research]. PMID- 26259294 TI - [Exposure to electromagnetic waves. Public health should not be a political issue]. PMID- 26259295 TI - Prevalence and Pattern of Autoimmune Conditions in Patients with Marginal Zone Lymphoma: A Single Institution Experience. AB - BACKGROUND: Increased risk of B-cell non-Hodgkin lymphoma (NHL) in patients with autoimmune diseases is a known fact. An association may exist between marginal zone lymphoma (MZL) and certain autoimmune conditions and vice-versa. METHODS: Herein, we present the analysis of a series of consecutive patients (n = 24) diagnosed with MZL at our institution between 2008-2014. Our series, analyzed both retrospectively and prospectively, consisted of a blend of nodal, extranodal and splenic MZL. The median age was 71.8 years; M/F ratio was 2:1. The presence of autoimmune conditions was compared to their documented prevalence in the general population and tested for statistical significance using both chi-square test (chi2) and Fisher test for small number of observations (95% confidence). A P-value < 0.05 was considered significant. FINDINGS: A total of 50% of MZL patients had documented autoimmune conditions. In addition, 3 of 24 patients presented with more than one autoimmune disease. Statistically significant differences in our MZL patients were recorded for immune thrombocytopenia [ITP] (P < 0.01), autoimmune hemolytic anemia [AIHA] (P < 0.01), Hashimoto thyroiditis (P = 0.037) and rheumatoid arthritis [RA] (P = 0.021). The difference did not reach statistical significance for systemic lupus erythematosus (SLE) and psoriasis. ITP and AIHA in our cohort were synchronous with MZL diagnosis in all patients, while all non-hematologic autoimmune conditions were metachronous and diagnosed prior to MZL. CONCLUSIONS: In the course of caring for patients with MZL, a number of associated autoimmune disorders are recognized. Knowing these entities is important not only for making a correct diagnosis, but also for being able to recognize certain clinical events occurring during the course of the disease. A catalogue of autoimmune disorders associated with this type of NHL is important as they can pose formidable clinical problems for the MZL patients and their physicians. PMID- 26259296 TI - An Unusual Cause of Acute-Onset Chest Pain: Spontaneous Pneumomediastinum. AB - Spontaneous pneumomediastinum (SPM) is the presence of air in the mediastinum without any precipitating factor or predisposing disease. It is an uncommon, usually benign condition predominantly seen in young males. It typically presents with chest pain or dyspnea. It occurs after intrathoracic pressure changes leads to alveolar rupture and dissection of air along the tracheobronchial tree. It is reported to occur in 1/30,000 to 1/40,000 hospital admissions. Despite its low incidence, SPM should be considered in the differential diagnosis of acute chest pain or dyspnea in young patients. Diagnosis requires a high index of suspicion, as evidence of its occurrence may not be present on examination or chest X-ray. Patients with SPM respond well to medical treatment, with no recurrence in the majority of cases. We report a case of a young healthy male who developed a spontaneous pneumomediastinum and pneumopericardium while playing volleyball and did well with conservative management. PMID- 26259297 TI - Genetic Anticipation in Familial Neuromyelitis Optica: Case and Literature Review. AB - OBJECTIVES: To describe genetic anticipation in a mother and daughter with antiaquaporin 4 (AQP4) antibody-positive neuromyelitisoptica (NMO). METHODS: Retrospective case review. RESULTS: A woman with onset of transverse myelitis at age 38 was found to have a positive AQP4 antibody during work-up of recurrent symptoms. Subsequently, she developed intermittent episodes of monocular vision loss with optic nerve involvement that were treated with intravenous methylprednisolone and chronic rituximab. Eighteen years after initial presentation, her 78-year-old mother, with a history of recurrent urinary tract infections, also developed monocular vision loss and her anti-AQP4 antibody was positive. Previous reports of genetic anticipation in familial NMO are identified and discussed. CONCLUSIONS: These cases highlight genetic anticipation in familial NMO. Disease onset can occur with a chronological age difference of as much as 40 years between parent and child. Patients with NMO should be counseled regarding the possibility of subsequent disease onset in family members, particularly parents, with significant differences in calendar or chronological year of onset. PMID- 26259298 TI - A Large-Sized Left Main Coronary Artery with Quadfurcation: A Rare Anatomy. AB - A 63-year-old woman presented to the emergency department with chest pain. She subsequently underwent an evaluation with a diagnostic coronary angiogram that demonstrated a rare coronary anatomy. Instead of its usual bifurcation into two main branches--a left anterior descending and a left circumflex artery--her left main coronary artery quadfurcated into four branches: a left anterior descending artery, a left circumflex artery, and two ramus intermedii arteries. Possible implications of this unusual finding are discussed. PMID- 26259299 TI - Azithromycin-Induced Cholestatic Hepatitis. PMID- 26259300 TI - Solitary Neurofibroma with Malignant Transformation: Case Report and Review Of Literature. AB - Solitary neurofibromas are rare tumors associated mainly with neurofibromatosis and widely described in the literature as benign. We report a case of a 55-year old female with no history of neurofibromatosis who presented with a slow growing, painless lump on her torso. Pathologic evaluation of the lesion after excisional biopsy revealed high mitotic activity and increased cellularity within the lesion as well as positive S-100 stain. She was diagnosed with solitary subcutaneous neurofibroma with features of malignant peripheral nerve sheath tumor transformation. To our knowledge, no other case of a solitary neurofibroma that transformed into a malignant tumor in this location was described in the literature. PMID- 26259301 TI - Perinephric Abscess with Fistula Formation to Descending Colon: A Case Report and a Review of the Literature. AB - A perinephric abscess (PA) is an uncommon clinical entity. We present a case of a patient with aknown chronic perinephric hematoma, complicated by infection, subsequently developing a fistula to the adjacent descending colon. To the knowledge of these authors, there are no reported cases of perinephric abscess fistula formation with the descending colon. CASE REPORT: A 50-year old woman with multiple medical comorbidities presented with gram negative sepsis and was subsequently found to have a cyst on her left kidney. Following CT-guided biopsy, an iatrogenic hematoma was formed and subsequently became infected. Radiographic evaluation revealed fistula formation between the abscess and the adjacent descending colon. Conservative management resulted in closure of the fistula without the need for further surgical management. DISCUSSION/CONCLUSION: Perinephric abscess (PA) formation can result in significant morbidity and mortalitywith complications including sepsis, renal failure and fistula formation. We present a first case report in which a PA fistualized with the descending colon following percutaneous drainage. PMID- 26259302 TI - Tackling Racial and Ethnic Health Disparities in Hospital Readmissions. PMID- 26259303 TI - Updates on Clostridium Difficile Infection. PMID- 26259304 TI - 50 Years Ago. From Connecticut Medicine. April 1965. Surgical Treatment Of Coronary Arterial Occlusive Disease. 1965. PMID- 26259306 TI - You, Your Health, and HAVEN. PMID- 26259307 TI - Uncomfortable Knowledge: Healthcare Disparities in Connecticut. PMID- 26259308 TI - CSMS: Tackling Healthcare Disparities With You. PMID- 26259309 TI - Accountability: Physicians Must Lead the Way. PMID- 26259311 TI - Rheumatic Musculoskeletal Complaints in Diabetes--Adding Another Dimension to a Multidimensional Disease! PMID- 26259312 TI - Ebola Virus Disease: Are We Prepared? PMID- 26259313 TI - Prevalence of Rheumatological Manifestations in Diabetic Population from North West India. AB - INTRODUCTION: An increased prevalence of rheumatological manifestations is recognised in diabetes and is a common source of disability. The relationship with other risk factors and glycaemic control is uncertain. We designed this study to find out the prevalence of rheumatological manifestations, association with various risk factors and to assess differences between type 1 and type 2 diabetes. MATERIAL AND METHODS: The study was conducted from Jan 2010 to Dec 2011 at tertiary care hospital. We recorded type of diabetes, various risk factors viz age, duration of diabetes, glycaemic control (HbA1C) and BMI and noted prevalence of various rheumatological manifestations by clinical examination, X-ray and if needed CT scan/MRI. We explored correlation between rheumatological manifestations and these variables using logistic regression. RESULTS: The prevalence of rheumatological manifestations was estimated at 570 per 1000 population. The manifestations were more common in type 1 diabetes (62.7%). The various complications observed in the present study were DISH (13%), Frozen Shoulder (20%), Dupuytren's Contracture (7.2%), Osteoarthritis (36.1%), Neuroarthropathy (2.9%), Chieroarthropathy (22.6%) and Flexor Tenosynovitis (8.1%). Among various risk factors, duration of diabetes (odd ratio: 5.127), BMI (odd ratio: 7.429) and age (odd ratio: 4.731) were common risk factors. Poor glycaemic control was also associated with increased prevalence of rheumatological manifestations. CONCLUSION: Rheumatologic manifestations are very common in diabetics and are associated with poor glycaemic control, BMI, duration of diabetes and age of the patients. PMID- 26259314 TI - Incidental Gall Bladder Carcinoma in Patients Undergoing Cholecystectomy: A Report of 7 Cases. AB - BACKGROUND: Carcinoma gall bladder accounts for 98% of all the gall bladder malignancies and is the sixth most common malignancy of the gastrointestinal tract worldwide. Incidental gall bladder carcinoma (IGBC) is an incidental finding of carcinoma diagnosed during a laparoscopic cholecystectomy or on histopathological examination of gall bladder specimen removed for benign gall bladder diseases. The incidence of IGBC is around 0.19 - 3.3% in the literature. OBJECTIVES: The aim of the present study was to report our experience with gall bladder cancers which were incidentally diagnosed during histopathological examination of cholecystectomy specimens done for benign gall bladder disease and follow up of the cases. MATERIAL AND METHODS: This study includes 270 cholecystectomy specimens which were removed, during June 2010 to July 2011 in a tertiary care hospital. The clinicopathological findings of cases with incidentally detected gall bladder cancers were recorded; age, sex, presenting symptoms, presence of gall stones and histologic grade and staging of tumours were included. Exclusion criteria included preoperative suspicion of malignancy before cholecystectomy. American joint committee on cancer (AJCC) staging system was used for staging incidental gall bladder carcinoma. RESULTS: In our study laparoscopy or open cholecystectomy was attempted in 270 cases during the one year period. Incidental gall bladder carcinomas were diagnosed in 7 cases (2.59%), with mean age of 50 years. Pain, vomiting, and dysphagia were the presenting complaints. USG revealed thickened gall bladder in 6 cases, and polyp in one case. Gall stones were seen in 6 cases. Histopathology showed moderately differentiated adenocarcinoma in all the cases. AJCC staging of gall bladder carcinoma revealed 6 cases in pT2 stage and pT1 a stage in one case. On follow up at 22 months, 6 cases were alive while one expired due to tumour metastasis. CONCLUSION: Prognosis of incidental gall bladder carcinoma is better, if diagnosed in early stages. PMID- 26259315 TI - Interpreting the Laboratory Reports for Vit D. AB - Importance for Vit D estimation has increased in the recent years due to its link to various diseases. Measurements of Vit D by different diagnostic laboratories is however not uniform. There is variation pertaining to assay methodology and also variation in the measurement of different metabolites of Vit D. There are also various confounders which influence Vit D assays and which in most instances are overlooked. Also a matter of concern regarding Vit D assays is the lack of assay standardisation. These factors contribute to the variation in the reports generated by the diagnostic laboratories. Therefore interpretation of Vit D reports needs proper understanding of these interfering factors and further reports need to be correlated substantially with the clinical findings. PMID- 26259316 TI - Tc 99m Sestamibi Scanning in Multiple Myeloma--a New look with SPECT-CT. AB - A variety of diagnostic tools including biochemistry, radiological imaging bone marrow studies and recently metabolic imaging with FDG PET are used for assessment of disease extent in myeloma. AIM: To evaluate the role of metabolic imaging with Tc99m Sestamibi (Mibi) SPECT-CT in Multiple myeloma. MATERIALS AND METHODS: Patients in various stages of Myeloma were scanned after 20mCi Tc99m Sestamibi was injected i/v. Whole body planar scans were obtained with a dual head gamma camera and SPECT-CT imaging was done. Images were analyzed for degree and extent of abnormal Mibi uptake, extent of lesions seen on low-dose CT and fusion of these images. RESULTS: 112 Whole body Sestamibi Scans were performed in 84 patients (46 Males; 38 Females). Out of these 24 (28.5%) were recently diagnosed cases (Pre-therapy); 35 (41.7 %) were follow-up cases who had received Chemotherapy in the past (Post-therapy), there were 2 cases (2.3%) of Smouldering Myeloma, 4 cases (4.7%) of Plasmacytoma, 13 cases (15.5%) of MGUS (Monoclonal gammopathy of Unknown Significance) and 3 cases (3.6%) of suspected Myeloma (not biopsy confirmed). Myeloma lesions showed good concentration of Mibi. Additionally, the CT scan component of SP.ECT-CT allowed visualization of osteolytic lesions of myeloma. Mibi uptake becomes positive on scan earlier than radiological changes and in follow-up cases, the presence or absence of Mibi uptake could differentiate active from old burnt-out lesions. Whole body scan could detect additional lesions in Plasmacytoma patients. Patients of MGUS showed poor concentration of Sestamibi. CONCLUSION: Whole body Sestamibi Imaging (WBSI) is very useful for evaluating the extent of disease in multiple myeloma. Being a metabolic imaging modality it is superior to radiological (X-ray or CT) assessment alone, and where FDG PET scan is not available, it is a valuable tool for myeloma assessment at a much lower cost. PMID- 26259317 TI - A Case of Chronic Back Pain. PMID- 26259318 TI - Ebola Virus: Another Challenge from the Deadly Viral Brigade. AB - Ebola viruses are the causative agents of a severe form of viral haemorrhagic fever in man, designated Ebola haemorrhagic fever, and are endemic in regions of central Africa. The recent west African outbreak of Ebolavirus has brought this filoviral infection again in limelight, Indian government has issued guidelines to various airports to screen travelers coming from Africa and middle east Haj pilgrims to keep a check on this highly virulent infection. This viral hemorrhagic disease has remained confined majorly to Africa but its high outbreak potential makes it essential for all infectious disease clinicians and people dealing with travel medicine to be cautious. Management of these patients with symptomatic therapy is the current strategy which is followed. There is absence of any effective vaccine so further research is warranted in this direction. PMID- 26259319 TI - Depressive Disorders in Indian Context : A Review and Clinical Update for Physicians. AB - Depression is a common, treatable disorder which continues to remain under detected in the primary care settings. With an average national deficit of 77% for psychiatrists in India, there is a need to mobilise more resources to deal with depressive disorders. Therefore, it is pertinent that the physicians are sensitised and trained for recognition and treatment of depressive disorders. Patients with mild to moderate depression, non-psychotic or somatised depression can be managed in primary care settings by general physicians. Unless specifically screened, depression may remain under-recognised and untreated in primary care/medical settings. The article reviews the available Indian research on depression and provide a clinical update to screen, diagnose and manage depression, especially aimed at physicians. PMID- 26259320 TI - Isolated Sixth Cranial Nerve Palsy--An Uncommon Presenting Feature of Multiple Sclerosis. PMID- 26259321 TI - An Unusual Site of Renal Artery Stenosis. PMID- 26259322 TI - Roth Spots in Chronic Myeloid Leukaemia. PMID- 26259323 TI - Pulmonary Infiltrates with Eosinophilia-Allergic Granulomatosis of Churg and Strauss. PMID- 26259324 TI - A Tale of Deviation. AB - Unilateral isolated Hypoglossal nerve palsy may result due to neoplasia, trauma, infections, autoimmune or vascular causes. We report a 52 year old male who presented with right hypoglossal nerve palsy and on evaluation was diagnosed to have prostatic malignancy with metastasis to the base of skull. Unilateral hypoglossal nerve palsy as the presenting feature of carcinoma prostate is rarely described.To the best of our knowledge, this is the third case report of unilateral hypoglossal palsy as a manifestation of prostatic carcinoma. PMID- 26259325 TI - Gastric Antral Vascular Ectasia. AB - Iron deficiency anaemia secondary to gastrointestinal bleeding is very common in the elderly. Gastric antral vascular ectasia (GAVE) syndrome, also known as watermelon stomach is an uncommon but significant cause of acute or chronic gastrointestinal blood loss in the elderly. It is characterised endoscopically by "watermelon stripes." It is more common in females than males, and manifests mostly as iron deficiency anaemia due to the gradual blood loss. Pathogenesis is unknown though several humoral factors have been proposed. Diagnosis is based on the clinical history and endoscopic appearance and histological changes. We describe elderly patient who presented with haematemesis and iron deficiency anaemia and was diagnosed to have GAVE and was treated successfully with endoscopic band ligation. PMID- 26259326 TI - Apert Syndrome. AB - Apert syndrome is one of the craniosynostosis syndromes which, due to its association with other skeletal anomalies, is also known as acrocephalosyndactyly. It is a rare congenital anomaly which stands out from other craniosynostosis due to its characteristic skeletal presentations. PMID- 26259328 TI - Prof. Sir Ravindra N Maini. PMID- 26259327 TI - Diagnostic Tests in Neoplastic Meningitis: Lessons Learnt from Three Patients. AB - Neoplastic meningitis (NM) poses diagnostic challenges and investigations need to be chosen carefully. We present three cases of NM with distinct learning points. In case 1, MRI was diagnostic of melanosis; in case 2, ventricular CSF showed malignant cells when lumbar CSF repeatedly failed to show them; and in the third, whole body PET scan diagnosed the tumour when other tests were negative. A comparative evaluation of various diagnostic modalities used in suspected NM is provided. PMID- 26259329 TI - Hakaru Hashimoto. PMID- 26259330 TI - Rabies--"Milwaukie Protocol". PMID- 26259331 TI - A Case of Complicated Falciparum Malaria with Treatment Failure to Artemisinin Combination Therapy. PMID- 26259332 TI - A Girl with Recurrent Pleural Effusion: Immunological Rebound or Isoniazid Induced Lupus? PMID- 26259333 TI - Rhabdomyolysis Induced Acute Renal Failure: A Rare Complication of Falciparum Malaria. PMID- 26259334 TI - Guillain Barre Syndrome and Malaria. PMID- 26259335 TI - Ethics, Evidence-Based Practice, and Economics: The Metrics of Quality. PMID- 26259336 TI - An Incentive Pay Plan for Advanced Practice Registered Nurses: Impact On Provider and Organizational Outcomes. AB - Advanced practice registered nurses (APRNs) are integral to the provision of quality, cost-effective health care throughout the continuum of care. To promote job satisfaction and ultimately decrease turnover, an APRN incentive plan based on productivity and quality was formulated. Clinical productivity in the incentive plan was measured by national benchmarks for work relative value units for nonphysician providers. After the first year of implementation, APRNs were paid more for additional productivity and quality and the institution had an increase in patient visits and charges. The incentive plan is a win-win for hospitals that employ APRNs. PMID- 26259337 TI - A Self-Efficacy Scale for Clinical Nurse Leaders: Results of a Pilot Study. AB - Introduced in 2003, the Clinical Nurse Leader (CNL) role is the first new nursing role introduced in more than 30 years. The hallmark of CNL practice is the management of client-centered care and clinical excellence at the point of care. As part of multifaceted efforts to implement the CNL role, understanding how an individual's self-efficacy with the identified role competencies changes over time has important implications for individuals, educational programs preparing CNLs, and health care organizations employing CNLs. In this study, preliminary psychometric analyses assessing the construct validity, reliability, and discriminant validity for a new state-specific scale (CNL Self-Efficacy Scale) that assesses nurses' perceptions of their ability to function effectively as a CNL are reported. Because self-confidence is a key predictor of successful role transition, job satisfaction, and job performance, measuring individuals' self confidence with the core competencies associated with the CNL role over time will be important to gain the full benefit of this innovative, unit-based advanced generalist role. PMID- 26259338 TI - A Descriptive Analysis of Implicit Rationing of Nursing Care: Frequency and Patterns in Texas. AB - The frequency and patterns of implicit rationing of nursing care in the United States are not known. The purpose of this study was to examine the phenomenon of implicit rationing among nurses in Texas. Implicit rationing was measured using a 31-item survey instrument adapted from the parent instrument originating in Switzerland. Some degree of rationing on at least one of the nursing care activities was reported by almost all of the respondents and most rationed multiple activities. Rationing preference patterns favor completion of activities directed to meet immediate physiological needs over other activities. If the relationships documented in other countries between implicit rationing and adverse patient outcomes are also present in the United States, then implicit rationing may serve as an important quality indicator. PMID- 26259339 TI - Understanding Health and Payment Reform--Essential for the New World of Nursing: An Interview with Betty Rambur. PMID- 26259340 TI - Meeting The Future of Nursing Report Recommendations: A Successful Practice Academic Partnership. AB - In collaboration with the University of Texas at El Paso, nurse leadership at Del Sol Medical Center implemented an internship program for nursing students in the final semester of a bachelor of science in nursing (BSN) program. The medical center experienced an increase in the proportion of BSN-prepared nurses, decreased orientation full-time equivalents (FTE), and lowered operating costs. The university experienced highly satisfied and competent new graduate nurses. The nurse interns averaged a 91.9% in-hospital registered nurse (RN) competency completion rate during the internship. All interns accepted a RN position at the medical center. Total savings for salaries, benefits, and recruitment fees at the medical center were $599,040 with a total FTE savings of 23.4 FTEs per week, over 10 weeks. PMID- 26259341 TI - Health Care in the Community: Developing Academic/Practice Partnerships for Care Coordination and Managing Transitions. AB - The delivery of health care is quickly changing from an acute care to a community based setting. Faculty development and mastery in the use of new technologies, such as high-definition simulation and virtual communities are crucial for effective student learning outcomes. Students' benefits include opportunities for hands-on experience in various patient care scenarios, realtime faculty feedback regarding their critical reasoning and clinical performance, interdisciplinary collaboration, and access to a nonthreatening learning environment. The results of this study provide some evidence of the benefits of developing faculty and nursing curricula that addresses the shift from an ilness-based, acute hospital model, to a community and population health-based preventive model. PMID- 26259342 TI - Too Many, Too Few, or Just Right? Making Sense Of Conflicting RN Supply and Demand Forecasts. AB - Forecasts of future supply and demand of health professionals are tools to guide policy, not a final statement about how the world will be in the future. Recent forecasts of RN supply and demand vary widely and are incredibly confusing for nurse leaders, nurse educators, and policymakers. To effectively incorporate forecasts into policy and planning, one must understand the structure of the forecasts and underlying assumptions. One should treat all forecasts cautiously, and use them as guides to policy rather than definitive future outcomes. PMID- 26259343 TI - Reframing Political Differences: One Conversation at a Time. AB - The profession of nursing, by it's very nature, is wrought with significantly complex moral and political disagreements. These issues cannot simply be avoided by being relegated to private discussions because their resolution is crucial to the common good. It is important for nurses to develop skills in public discourse if we are to bridge the political divide and influence local, state, and national policy. Failure to do so will leave us with ineffective and dismissed voices. PMID- 26259344 TI - Improving Pneumococcal Immunization Rates Among Hospitalized Adults. AB - The morbidity and mortality associated with pneumococcal pneumonia can be prevented with access to vaccines and treatment. The purpose of this quality improvement project was to examine how the utilization of the discharge computer entry order set with an electronic pneumococcal vaccine screening tool, pharmacy notifications, and nursing tasks increased the vaccination rates among discharged patient population sufficiently. Changing the process of when the patient is screened for the pneumococcal vaccine and utilizing functions of the electronic medical record greatly improved the immunization rate of discharged patients. Due to the success of this process improvement project, other immunizations given during hospitalization are being screened and administered at discharge. PMID- 26259345 TI - Why Nurse Staffing Matters: A Moral Imperative. AB - Safe nurse staffing is undeniably linked to patient safety and satisfaction, workforce satisfaction and safety, and cost savings. A nationwide mandate must be driven toward the use of electronic staffing and scheduling systems that take into consideration the patient's real-time specific needs This system must be matched to the most appropriate nurse with the ability to provide care safely for all the patients in his or her total assignments. These patient care assignments should be designed in partnership with managers and staff RNs. Only then will we reverse the trend of staffing-related patient deaths and injury in U.S. hospitals. PMID- 26259351 TI - Legislative Update. PMID- 26259358 TI - I received a copy of my employee handbook ... now what? PMID- 26259360 TI - Bullying in Healthcare. A call to action to stop lateral violence. PMID- 26259361 TI - Residency Programs Aren't Just for New Graduates. PMID- 26259362 TI - ARNP Full Practice Authority: What's it all About? PMID- 26259363 TI - Tallahassee 2015: A Call to Action for Nursing. PMID- 26259364 TI - A Tribute and a Call to Action to our New Graduates. PMID- 26259367 TI - Considering Mindfulness Practice as a Primary Intervention for Bullying and Burnout of Nurses. PMID- 26259377 TI - Dealing with Mean Girls in Your Office? You're Not Alone. PMID- 26259379 TI - Ethics and Nursing. PMID- 26259378 TI - Statewide Task Force on Prescription Drug Abuse and Newborns Update: Neonatal Abstinence Syndrome Data Summary. PMID- 26259380 TI - Where are the Florida Clinical Nurse Specialists? PMID- 26259381 TI - Another One of Our Own is Gone Too Soon. PMID- 26259382 TI - Penetrance and phenotypic effects of C/T polymorphism at 1595 position in exon 5 of the TRAIL gene among prostate cancer patients in Pakistani population. AB - It is becoming progressively more understandable that variations within the sequence of tumor suppressor genes and oncogenes may contribute to cancer progression. Increasingly it is being realized that cancer cells get resistant to pro-apoptotic signals and evidence has started to shed light on the fact that nucleotide polymorphisms may lead to suboptimal apoptotic capacity and therefore increased cancer risk. It has previously been shown that there is a relationship between C/T polymorphism at 1595 position in exon 5 of the TRAIL gene and cancer however rapidly accumulating data cannot be extrapolated to other populations due to intra- and inter-ethnic variability. The study is focused on the C/T polymorphism at 1595 position in exon 5 of the TRAIL gene in prostate cancer patients diagnosed in local population in Pakistan. 126 prostate cancer patients and 91 control subjects participated in this study. 5ml venous blood was taken from participants with informed consent. DNA was extracted using standard organic methods. PCR-RFLP analysis was done for C/T polymorphism at 1595 position in exon 5 of the TRAIL gene using site specific primers and restriction enzyme. The results were statistically evaluated in SPSS14. In this particular study it was found that there was no significant difference in major allele C genotype between patients and controls, p value > 0.05. Similar statistically non-significant difference was observed for T allele genotype in the patient and control groups. However the heterozygous genotype CT was significantly higher, p value 0.053 ( 0.05), in prostate cancer patients as compared to controls. This is the first study providing a clue of relationship of C/T polymorphism role in prostate cancer development and progression in our population. PMID- 26259383 TI - Primary yolk sac tumor of endometrium: report of two cases and review of literature. AB - Primary YST of the endometrium is very rare, therefore there is no guideline for treatment. We report two cases of endometrial YSTs presenting different symptoms and showing different prognoses and discuss the clinical management of these tumors. The present report shows first time that bone and lung metastasis in primary YSTs of endometrium. As the number of reported cases with endometrial YSTs, more information about the prognosis of the disease may be obtained. PMID- 26259384 TI - Malignant transformation of mature cystic teratoma of the ovary: a case series. AB - The aim of this study was to analyze the patients with malignant transformation (MT) arising in mature cystic teratoma of the ovary (MCTO) and evaluate the clinicopathologic features, managements, and prognosis of these cases. The records of the patients with MT arising in MCTO who were treated at our hospital were reviewed retrospectively. The demographic features, presenting symptoms, preoperative ultrasonographic evaluations, surgical treatments, pathological findings, adjuvant therapies, follow-up outcomes, and survival time were examined. Eighteen patients with MT arising in MCTO were detected during the study period. The incidence rate of MT was 0.404% of all MCTO and squamous cell carcinoma was the most common histologic type (66.7%). The median age of the patients was 48 (range, 28-79) and the mean tumor size was 12 cm. Eleven patients (61.1%) were classified as stage IA, 1 (5.6%) as stage IC, 1 (5.6%) as stage IIC, 4 (22.2%) as stage IIIC, and the remaining 1 (5.6%) as stage IV. The overall 5 year survival rate was 66.7%. MT of MCTO is a rare occurrence entity and early detection and complete surgical staging are cardinal for survival. Additionally, this malignancy usually occurs in postmenopausal women and the high tumor diameter may be associated with MT. PMID- 26259385 TI - Peripheral odontogenic fibroma: a rare gingival neoplasm with clinico pathological differential diagnosis. AB - The peripheral odontogenic fibroma (POdF) is a rare gingival neoplasm, characterised by relatively mature collagenous fibrous tissue and varying amounts of odontogenic epithelium. It can be described as a slow growing, firmly attached, solid and smooth gingival mass which may be present asymptomatically for years, which may cause displacement of adjacent teeth. The purpose of this article is to discuss a case of POdF, occurring in the maxillary anterior region, with detailed clinico-pathological differential diagnosis to clarify characteristic features of various gingival overgrowths to enhance easy identification. PMID- 26259386 TI - Krukenberg carcinoma metastasized from stomach resembling mucinous cystadenocarcinoma of the ovary. AB - The ovaries are common site of metastasis in a variety of primary neoplasms. Multiple tumors such as breast, lung, and pancreas have been reported to metastasize to the ovary, however; the colon and stomach are the most common primary cancer sites that of ovarian metastasis. An ovarian mass mostly originates from its self-tissue, but sometimes it can be a metastasis of a gastrointestinal system tumor. Such cases are often misdiagnosed as primary ovarian cancers. A 42-year-old woman was admitted to our hospital with pelvic pain. She had a history of her complaints for two months. Bilateral large ovarian mass was detected in transvaginal ultrasound. Laparotomy was performed, the pathologist suggested inspection of the stomach after the frozen section analysis; therefore, an irregular mass on the stomach was detected. The general surgeon was attended to the operation, and an inoperative stomach tumor was reported by the general surgeon. After that due to the partial obstruction of jejunum, a gastrojejunostomy was performed. It is in fact difficult to distinguish between metastatic mucinous carcinomas and primary mucinous carcinomas of the ovary, due to the similar appearance of as cystic tumors on gross examination. The clinicians should be aware of the likely concomitant gastrointestinal system tumor when a large and bilaterally mass was detected on physical examination. This case also reminds that a systemic examination is necessary even if the large ovarian tumors suspicious of primary malignancy were noticed. PMID- 26259387 TI - Tumor molecular profiling in the treatment of refractory cancers. AB - INTRODUCTION: Molecular profiling (MP) has been used as a technique to identify treatment regimens for individual patient's cancer. The results of MP has been used to guide targeted therapy specific to each patient's tumor that resulted in a longer progression free survival (PFS) compared to the last conventional treatment. This study aims to provide further data to delineate the PFS of patients who get treated with targeted therapy based on MP. METHODS: A retrospective chart review was performed. The patients were greater than 18 years of age refractory to at least one standard treatment and enrolled in the study: "A Clinical Data Registry Study of Patients with Advanced Refractory Cancers Electing OncInsights as a Method to Support Physician Choice of Drug Therapy". The location is a West Michigan Hematology-Oncology private practice during the period of 07/2010-02/2013. We considered the molecular profiled treatment regimen a success if the PFS ratio was >= 1.3. RESULTS: 18 patients were included in the study. 55% were male and 45% were female with median age of 57.67 +/- 12.02 at the time of diagnosis. 4/18 (22%) patients achieved a PFS ratio >1.3. The patients with a PFS ratio >= 1.3 included GIST (imatinib- > sunitinib); angiosarcoma (docetaxel- > sorafenib, pravastatin); thymoma (paclitaxel- > desatinib); and angiosarcoma (gemcitabine- > sunitinib). CONCLUSION: This study demonstrates the potential value of molecular profiling in patients refractory to prior chemotherapeutic agents in a community setting. Continued work on rapid implementation of molecular profiling earlier in the care of oncology patients continues to be a future goal. PMID- 26259388 TI - Strategies used in the clinical trials of gene therapy for cancer. AB - Advances in understanding and manipulating genes have set the stage for scientists to alter a person's genetic material to prevent or treat diseases. Over the past decade, somatic gene therapy has been increasingly applied in clinical trials where the genetic material (DNA and RNA) introduced into a person's cell. Mutation and inactivation of the tumor suppressor genes are the unified concept of the development of tumor in humans. Therefore, researchers have discovered potential of gene therapies in the treatment of cancer. Among the clinical trials of gene therapy conducted so far, approximately 66% were for the treatment of cancer which includes cancer of prostate, head and neck, kidneys, lungs, breast and skin. Introducing a wild type p53 gene, enhancing the immune system to protect against the cancer cells, enhancing the apoptosis of cancer cells and inhibiting the process of angiogenesis in the tumor are some of the clinical trials that are achieved through the gene therapy. Broad spectrum of delivery constructs, including viral vectors, liposomes, cationic polymers and dendrimers, cell-penetrating peptides, semiconductor quantum dots, and gold and magnetic nanoparticles have been investigated. A well designed vector is the most forward approach to increase the safety of gene therapy. Though, Gendicine and Oncorine have been marketed, gene therapy is still in its infancy stages in cancer research. More experimental and clinical trials using well-designed and effective doses of vectors are needed to ensure the therapeutic efficacy of gene therapy for its clinical use against a wide variety of cancers. This review article discuses about the various strategies used in clinical trials of gene therapy for cancer. PMID- 26259389 TI - Role of telomerase in anticancer activity of pristimerin in prostate cancer cells. AB - Pristimerin (PM) is a quinonemethide triterpenoid present in various plant species with strong antiprolifertive and proapoptotic activities in cancer cells. The effect of PM on telomerase which is reactivated in most cancers including carcinoma of the prostate (CaP) has not been studied. We investigated the effect of PM on the expression of human telomerase reverse transcriptase (hTERT) gene that codes for the catalytic subunit of the telomerase holoenzyme complex in prostate cancer cell lines LNCaP and PC-3 cells. The inhibition of cell proliferation and induction of apoptosis by PM in both cell lines was associated with the inhibition of hTERT mRNA expression, suppression of native and phosphorylated hTERT protein and hTERT telomerase activity. The ablation of hTERT expression increased the sensitivity of cancer cells to PM. In addition, results also revealed that the inhibition of hTERT expression is attributed to the inhibition of transcription factors SP1, c-Myc and STAT3 and protein kinase B/Akt which regulate hTERT transcriptionally and post-translationally, respectively. These data provide evidence that telomerase is a potential target of PM in prostate cancer. PMID- 26259390 TI - Immunostimulant and chemoprotective effect of vivartana, a polyherbal formulation against cyclophosphamide induced toxicity in Swiss albino mice. AB - The aim of the study is to develop a technology for cost effective immunomodulator from natural products to combat adverse effects during cancer chemotherapy. In the present study, the immunomodulatory efficacy of Vivartana, a poly herbal formulation in immunosuppressed animal model induced by cyclophosphamide (CTX) and its comparison with standard herbal immunostimulators Chyawanprash and Brahma Rasayana was investigated. The effect of Vivartana (500 mg/kg x bw) (p.o.), Chyawanprash (20 mg/kg.bw) (p.o.) and Brahma Rasayana (20 mg/kg x bw) (p.o.) on hematological parameters, relative organ weight, Bone marrow cellularity and alpha-esterase activity were determined in Swiss albino mice by using the standard methods. Among the herbal formulations Vivartana showed the maximum number of leukocytes (13150 cells/mm3) on the 15th day. The leukocyte count in Vivartana treated CTX induced group shows significant increase (5375 cells/mm3) when compared with CTX alone induced group (3358 cells/mm3) on the same day. The Vivartana treated CTX induced group shows increase in the hemoglobin level compared with the CTX induced group. Moreover, Vivartana treatment prevented the loss of organ weight in the CTX induced group by the enhancement of spleenocytes on the 7th day and thymocytes on the 11th day. Similarly the lowered bone marrow cellularity and number of alpha-esterase positive cells in CTX induced group were restored in the Vivartana treatment. Treatment with vivartana also exhibits hepatoprotective activity by regulating the SGOT and SGPT levels in CTX induced group. The study indicates that Vivartana has the considerable potential as an immunostimulant and chemoprotectant against CTX induced immunosuppression in Swiss albino mice. PMID- 26259391 TI - Prevalence of quid-induced lichenoid reactions among western Indian population. AB - OBJECTIVE: Betel quid and areca nut chewing is widely prevalent in many parts of Asia and Asian migrant communities in the world. Due to the carcinogenicity associated with quid and areca nut we developed an interest to study the prevalence of quid induced oral lichenoid reactions in the population of western India. METHODS: A total population of 4981 males and females was screened for tobacco use and the prevalence of lesion in 86 quid users was seen. The lesions which met the selection criteria of oral lichenoid reaction were identified. RESULTS: Prevalence of 10.4% oral lichenoid reaction was seen in all quid users and 28.12% in subjects who used tobacco with quid. Statistical analysis yielded a high degree of correlation between occurrence of lesion and quid habit. CONCLUSIONS: The clinician should be aware of the occurrence of such lesions and their associated clinical behaviour and malignant potential, if any. A close monitoring/ follow-up should be done. PMID- 26259392 TI - In human alleles specific variation of MTHFR C677T and A1298C associated "risk factor" for the development of ovarian cancer. AB - Etiopathology of tumor biology is highly complex and ovarian cancer is one of the important gynaecological neoplasia associated with high risk of mortality rate. Methlenetetrahydrofolate reductase (MTHFR) mutation are commonly linked to folate metabolism with increased risk factor for the development of neural tube defects, recurrent pregnancy loss and development of several type of cancer but genetic interaction between two alleles of MTHFR has been poorly defined in ovarian cancer in India. Hence, present study becomes imperative with the aim to assess the alleles frequency of MTHFR (C677T & A1298C) gene polymorphism using PCR based RFLP analysis. The O.R at 95% confidence interval (C.I.) was computed between cases and their respective controls to determine "risk factor". Interestingly, our findings reveals highly significant (p < 0.001) difference in heterozygous (CT) condition of C677T allele by computing odd ratio (0.12 at 95% C.I, 0.021 0.0428; P for trend = 0.001) in controls and (0.34 at 95% C.I, 0.074-1.530; P for trend = 0.198) cases, suggesting that three time increase the "risk factor" for genetic susceptibility of MTHFR "T" allele for the development of ovarian carcinoma. PMID- 26259393 TI - Unilateral angiokeratoma of vulva: a rare clinic entity. AB - The aim of this study is to present a very rare dermatologic condition of the vulva. Angiokeratoma is a benign dilation of ectatic thin-walled blood vessels and congested capillaries in the superficial dermal layer of skin. It occurs predominantly in men and extremely rare in women. Angiokeratoma presents as single or multiple papular lesions on the vulva with smooth or verrucous surface. These lesions are easily confused with infectious disease, inflammatory lesions, and epithelial tumors. In this report, we presented a 42 year old unmarried woman who was admitted to our clinic with complaints of two papuler lesions of the right labium majus with vaginal discharge, vulvar pruritis, and vulvar edema. She had been previously treated with different local or systemic antiinfectious agents and her screening tests for sexually transmitted disease were negative. The genital examination showed a very thinned, hyperemic and edematous vulvar skin with two lesions measured 0,5-1 cm in diameter on the right labium majus. The surface of the lesions was partly uneven and partly veined. A local excision was performed. Histological examination showed hyperkeratosis, papillomatosis and acanthosis with dilated vascular areas in the dermis and the specimen revealed angiokeratoma. In conclusion, we should be aware of this clinical entity to make the differential diagnosis of a lesion on the vulva. PMID- 26259394 TI - Dr. Samokhotskiy's method of healing inflammation by the analysis and regulation of blood electrolyte balance. AB - An overview of a little-known method, which was discovered by Dr. Alexander S. Samokhotskiy, for treatment of gangrenous, traumatic, and postoperative inflammation, sepsis and some other diseases, was represented. Dr. A. S. Samokhotskiy carried out numerous animal experiments and clinical trials and found that application of wet bandages and/or intravenous injection of solution containing trivalent chromium ions (Cr3+), alum, resorcinol, sodium salicylate, lactate buffer, colloidal sulphur, thioglycolic acid and glutathione with adding KCl, MgCI2, CaCl2 or NaCl solutions can heal inflammation of various etiology. Intravenous injections of particular therapeutic solution containing Na+, K+, Ca2+ or Mg2+ ions were administered in dependence on concentration of these ions in patient's blood plasma. Thousands of patients, many of them with fatal afflictions, where other methods were helpless, were healed by Dr. A. S. Samokhotskiy with the help of his method. Purpose of this publication is to inform the international medical community with the Dr. A. S. Samokhotskiy's discovery and initiate further research in this area. PMID- 26259395 TI - Versatility of Radial Forearm Free Flap for Intraoral Reconstruction. AB - INTRODUCTION: The radial forearm free flap has an important role in reconstruction of the oncologic defects in the region of head and neck. OBJECTIVE: The aim was to present and evaluate clinical experience and results in the radial forearm free transfer for intraoral reconstructions after resections due to malignancies. METHODS: This article illustrates the versatility and reliability of forearm single donor site in 21 patients with a variety of intraoral oncologic defects who underwent immediate (19 patients, 90.5%) or delayed (2 patients, 9.5%) reconstruction using free flaps from the radial forearm. Fascio-cutaneous flaps were used in patients with floor of the mouth (6 cases), buccal mucosa (5 cases), lip (1 case) and a retromolar triangle (2 cases) defects, or after hemiglossectomy (7 cases). In addition, the palmaris longus tendon was included with the flap in 2 patients that required oral sphincter reconstruction. RESULTS: An overall success rate was 90.5%. Flap failures were detected in two (9.5%) patients, in one patient due to late ischemic necrosis, which appeared one week after the surgery, and in another patient due to venous congestion, which could not be salvaged after immediate re-exploration. Two patients required re-exploration due to vein thrombosis.The donor site healed uneventfully in all patients, except one, who had partial loss of skin graft. CONCLUSION: The radial forearm free flap is, due to multiple advantages, an acceptable method for reconstructions after resection of intraoral malignancies. PMID- 26259396 TI - The Influence of Liners on the Pulp Inflammation. AB - INTRODUCTION: The study included application of liners and dental composites in to cavities of six experimental animals-rabbits (Oryctolagus cuniculus). OBJECTIVE The aim of the study was to investigate rabbit dental pulp response to different liners. Methods Cavity preparation for class V were made on the maxillary central incisors and one lower incisor, while the second lower incisor served as a control tooth. These teeth were restored with the use of one of the following liners--Calcimol LC, ANA Liner and Fuji II LC Improved, and Ceram-X mono dental composite. After an observation period of five days animals were sacrificed and prepared for histological analysis.The existence and degree of the pulp inflammation was determined by using a light microscope. RESULTS: Results showed that the used liners do not cause distortion of the structure and continuity of the odontoblastic layer. Inflammation was not registered in the control group, while in each group of tested materials one tooth with mild signs of hyperemia was registered. Results showed that all three tested liners demonstrated favorable effects on the pulp of the tooth and did not lead to inflammatory reactions. CONCLUSION: Histological analysis of the dental pulp of experimental animals suggests that the liners used in this study do not compromise the integrity of the odontoblastic layer, if it is applied over a thin layer of dentin. In each group of tested materials one tooth with mild signs of hyperemia and vasodilation was registered. PMID- 26259397 TI - Pharyngeal Airway Changes after Bimaxillary Orthognathic Surgery--Preliminary Results. AB - INTRODUCTION: Dentofacial deformity, a deviation from normal facial proportions and dental relationships, is corrected by jaw repositioning in all three spatial planes, which changes the position and tension of the surrounding tissues, bones and muscles. These changes may also affect the dimensions of the pharyngeal airways (PA). OBJECTIVE: The aim of this study was to evaluate and compare three dimensional PA changes in patients treated by a combination mandibular set back/maxillary advancement versus patients that had bimaxillary advancement with genioplasty. METHODS: The sample consisted of 7 patients treated by combined mandibular set-back/maxillary advancement and 7 patients treated with bimaxillary advancement surgery. Nasopharyngeal (NP) volume, oropharyngeal (OP) volume and the area of maximum constriction (AMC) in the OP were measured on CBCT scans (2 mA/120 kV/12" FOV) taken before (T1) and 3 months after surgery (T2). Paired samples t-test was used for analyzing statistical significance of changes (p <= 0.05). RESULTS: OP volume and AMC increase after bimaxillary advancement was statistically significant, while for the mandibular set-back group the increase was non-significant. NP volume was not reduced in any of the two groups. No significant differences in PA dimensions were found between groups at neither T1 nor T2 time points. CONCLUSION: Results suggest that the combination of mandibular set-back/maxillary advancement did not reduce airway dimensions, while bimaxillary advancement surgery led to a statistically significant increase in the OP dimensions. PMID- 26259398 TI - Legionella pneumophila in Bronchoalveolar Lavage Samples of Patients Suffering from Severe Respiratory Infections: Role of Age, Sex and History of Smoking in the Prevalence of Bacterium. AB - INTRODUCTION: Legionellapneumophila is the most commonly detected cause of legionellosis, which is an acute respiratory tract infection with high morbidity and mortality rates. OBJECTIVE: The aim of this study was to investigate the prevalence rate of L. pneumophila in bronchoalveolar lavages and study the role of sex, age and history of smoking as risk factors or susceptibility to the bacterium. METHODS: One hundred bronchoalveolar lavage samples were collected from the Iranian health centers and immediately transferred to laboratory. The samples were cultured and those that were L. pneumophila positive were subjected to PCR method with respect to the 16S rRNA gene. RESULTS: Twelve out of 100 samples were positive for L. pneumophila (12%). Patients older than 70 years had the highest incidence of L. pneumophila (17.77%). Prevalence of L. pneumophila in male and female patients was 14.81% and 8.69%, respectively. Total incidence of L pneumophila in patients with and without history of smoking was 18% and 6%, respectively. There were significant differences in the incidence of bacterium between groups of our study. CONCLUSION: Sex, age and history of smoking are predominant risk factors for the occurrence of L. pneumophila. However, more studies should be undertaken to confirm these results. PMID- 26259399 TI - Splenomegaly in Sarcoidosis: Frequency, Treatment, Prognosis and Long-term Follow up. AB - INTRODUCTION: The splenic involvement is common in sarcoidosis, but its real frequency is still obscure depending doubtless on the method of splenomegaly detection. Splenomegaly may be accompanied with pain or anemia, leucopenia and thrombocytopenia. OBJECTIVE: The aim of this study was to investigate the frequency of splenomegaly related to clinical characteristics of sarcoidosis and to solve the dilemma--whether to introduce medicaments, and when to perform splenectomy. METHODS: The method of the study is a retrospective and prospective analysis of the patients'material. RESULTS: The study included 540 patients with sarcoidosis in a 20-year period. Of them, 26% had splenomegaly detected by computerized tomography screening. Splenomegaly was more frequently registered in the patients with a longer history of sarcoidosis (38%), as compared to those with a shorter history of the disease (23%) (p < 0.05). Splenomegaly was more frequently registered in the patients with other extrapulmonary lesions detected (33%) than in those who had no extrapulmonary manifestations of sarcoidosis (17%) (p < 0.01). Indications, possible benefits and complications of splenectomy were analysed in 11 sarcoidosis patients undergoing this intervention for various reasons, of which the follow-up period ranged from one to 20 years. CONCLUSION: Splenomegaly was more frequent in chronic cases or in the patients with established sarcoid lesions of other extrapulmonary organs.The primary treatment of uncomplicated symptomatic splenic sarcoidosis includes medicamentous therapy. Occasionally, splenectomy is required. Prognostically, splenomegaly indicates an unfavorable course of the disease. PMID- 26259400 TI - Adverse Effects of Pharmacological Therapy of Benign Prostatic Hyperplasia on Sexual Function in Men. AB - INTRODUCTION: The development of effective medications makes pharmacological therapy of BPH the dominant mode of treatment today. It improves urinary symptoms and prevents disease progression while producing side effects on male sexual function. OBJECTIVE: The aim of the study is to present the effects of BPH pharmacological treatment on the occurrence of sexually adverse effects in men: changes in sexual desire, erectile, ejaculatory and the orgasmic function. METHODS: A prospective study involving 156 BPH patients.The average age was 61.16 +/- 2.97. Four groups of 39 patients each were formed.The 4 groups were administered tamsulosin (alpha-blocker), finasteride (5-alpha reductase inhibitor), combination therapy (tamsulosin and finasteride) respectively, while the control group received no treatment. PSS-QoL, IIEF and MSHQ-EjD questionnaires were used to evaluate the symptoms of voiding and sexual function. Follow-up examinations were performed 3 and 6 months into treatment. RESULTS: Voiding symptoms improved in all groups receiving therapy. The side effects on the sexual function in all these groups include significant disorders of ejaculation and the orgasmic function. Ejaculation disorders: tamsulosin (-4.38 +/- 2.55; p < 0.001), combined therapy (-3.89+/- 2.84) and finasteride (-1.49 +/- 2.52). Orgasmic function disorders: tamsulosin (-1.03 +/- 1.94), combined therapy (-0.76 +/- 2.07) and finasteride (-0.54 +/- 1.68). Complete absence of ejaculation was experienced by 23% of patients on combined therapy, 15% on tamsulosin and 5% on finasteride. CONCLUSION: Pharmacological therapy of BPH improved voiding symptoms producing different effects on male sexual function. The main adverse effect on sexual function in men is the deterioration in ejaculation or the absence thereof. Clinical consideration of BPH should include the elements of male sexual function, patients' age, the characteristics and effects of each group of drugs. PMID- 26259401 TI - Nonmelanoma Skin Cancer in the Population of the City of Belgrade in the Period 1999-2011. AB - INTRODUCTION: Nonmelanoma skin cancers in the literature are mainly related to basal cell and squamous cell skin carcinoma. OBJECTIVE: The aim of the study was to determine the trend in the incidence of histological types of nonmelanoma skin cancers in the population of the city of Belgrade from 1999 to 2011. METHODS: From the Serbian National Cancer Registry we extracted all recorded cases of skin cancer in Belgrade from January 1st 1999 to December 31st 2011. Incidence rates were standardized by the method of direct standardization with the world population as the standard population. Trends and annual percentage change (APC) of incidence rate were calculated by performing joinpoint regression analyses. RESULTS: Incidence rate of nonmelanoma skin cancer showed significantly increasing trend between 1999 and 2006 with APC of 8.6% (95% Cl: 5.6-11.7), basal cell carcinoma increased with APC of 8.4% (95% Cl: 5.2-11.6) and squamous cell skin carcinoma with APC of 9.33% (95% Cl: 5.7-13.1). The incidence increased with age for both men and women, especially after the age of 60. CONCLUSION: Our results showed a continuously increasing incidence trend of both basal cell and squamous cell skin carcinomas in the population of the city of Belgrade between 1999 and 2011. Adequate primary and secondary prevention would certainly be successful in reducing this type of cancer in the future. PMID- 26259402 TI - The Presence of Some Humoral Immunologic Indicators and Clinical Manifestations in Cryoglobulin Positive Heroin Addicts without Evidence of Hepatitis Virus Infection. AB - INTRODUCTION: Cryoglobulins are single or mixed immunoglobulins that are subject to reversible precipitation at low temperatures. OBJECTIVE: The aims of this paper were: 1. Comparison of cryoglobulin positive (CP), cryoglobulin negative (CN) heroin addicts and the control group (CG) in terms of serum immunoglobulins IgG, IgA and IgM and complement components C3 and C4; 2. Comparison of CP and CN heroin addicts in terms of rheumatoid factor (RF) and circulating immune complexes (CIC); 3. Assessment of clinical manifestations in CP heroin addicts. METHODS: This is a comparative study of cases (outpatients) treated at the University Clinic of Toxicology in Skopje over 3.5 years, from January 2009 to June 2012. In this study 140 heroin addicts without HbsAg were examined, seronegative for HCV and HIV infections.They were divided into 2 groups: 70 CP and 70 CN heroin addicts. A previously designed self-administered questionnaire was used as a data source on participants. All heroin addicts underwent the following analyses: urea and creatinine in serum; creatinine in urine; proteinuria; 24-hour proteinuria; IgM, IgG, IgA, C3, C4; RF; CIC; creatinine clearance; ECG; toxicological analyses for opioids in a urine sample; cryoglobulins. In addition to these 2 groups, IgG, IgA, IgM, C3 and C4 were also examined in 70 healthy subjects (CG). RESULTS: The study showed that there was no statistically significant difference between CP, CN heroin addicts and CG regarding the concentration of IgA, IgG, IgM, C3 and C4, and between CP and CN regarding the concentration of CIC. There was significant difference between CP and CN regarding the concentration of RF. The following conditions were significantly more frequently manifested in CP than in CN heroin addicts: arthralgia, Raynaud's phenomenon, respiratory difficulties, neurological disorders, manifested skin changes, hematuria, 24-hour proteinuria levels, and decreased renal clearance. CONCLUSION: There were no differences in concentrations of IgG, IgA, IgM, C3, C4 and CIC, while there was a difference in concentration of RF between CP and CN heroin addicts. Clinical manifestations (arthralgias, Raynaud's phenomenon, respiratory, neurologic, renal disorders and skin changes) were more common in CP heroin addicts. PMID- 26259403 TI - Alcohol Consumption among Students--A Cross-Sectional Study at Three Largest Universities in Serbia. AB - INTRODUCTION: The prevalence of unhealthy alcohol use among university students is increasing in many countries. OBJECTIVE: The aim of the study was to investigate alcohol consumption and alcohol-related knowledge, attitudes and risky behaviors among Serbian university students. METHODS: The cross-sectional study was carried out at the three state universities from January to June in the academic year 2009/2010 and included 2,285 students of both genders. The students filled out a questionnaire consisting of 70 questions with respect to demographic and socioeconomic characteristics, their lifestyle habits, styles and attitudes, health assessment, as well as exposure to different risk factors. RESULTS: It was found that 77.7% of students drank alcohol occasionally, 4.6% of them consumed it on a daily basis. Friedman's test (p < 0.001) showed that students prefer drinking beer to all other alcoholic beverages. Students in Belgrade and students of Technical faculties are undisputed champions when it comes to how often they drink six or more drinks on a single occasion. Older students in Serbia drink more and get drunk more frequently. CONCLUSION: A high percentage of Serbian students consume alcohol, and even though they have their first drink at an early age, they generally drink less than students in many other countries. PMID- 26259404 TI - Primary Merkel Cell Carcinoma of the Eyelid-- Clinical, Histopathological, Immunohistochemical and Electron Microscopical Features: A Case Report. AB - INTRODUCTION: Merkel cell carcinoma (MCC) is a rare eyelid neoplasm which can cause significant diag- nostic and especially therapeutic challenges. CASE OUTLINE: This is the first documented report of the case of primary MCC of the eyelid in Serbia. CONCLUSION: The optimal therapy must be individualized in any given patient and, early diagnosis and meticulous follow-up are mandatory to achieve a long-term cure. PMID- 26259405 TI - Colorectal Adenocarcinoma Metastasizing to the Oral Mucosa of the Upper Jaw. AB - INTRODUCTION: Metastases to the oral cavity are uncommon, accounting for only 1% of all oral malignant tumors. When they occur they mostly originate from primary tumors of the lungs, kidney, breast and prostate. Oral metastases from the primary colorectal carcinoma are much more infrequent. CASE OUTLINE: We present an unusual case of a 78-year-old man with a soft tissue oral metastasis originating from the primary colorectal carcinoma.The patient was referred to the Department of Otorhinolaryngology, Head and Neck Surgery with an intraoral mass on the right side of the maxilla. The diagnosis was confirmed by histopathologic examination and immunohistochemical analysis. CONCLUSION: Oral metastases occur rarely and often can mimic much more common benign lesions, therefore they should be considered as a possibility in a differential diagnosis. PMID- 26259406 TI - Congenital Cervical Bronchogenic Cyst: A Case Report. AB - INTRODUCTION: Bronchogenic cysts are rare congenital anomalies of the embryonic foregut. They are caused by abnormal budding of diverticulum of the embryonic foregut between the 26th and 40th day of gestation. Bronchogenic cysts can appear in the mediastinum and pulmonary parenchyma, or at ectopic sites (neck, subcutaneous tissue or abdomen). So far, 70 cases of cervical localization of bronchogenic cysts have been reported. Majority of bronchogenic cysts have been diagnosed in the pediatric population. Bronchogenic cysts of the cervical area are generally asymptomatic and symptoms may occur if cysts become large or in case of infection of the cyst. The diagnosis is made based on clinical findings, radiological examination, but histopathologic findings are essential for establishing the final diagnosis. Treatment of cervical bronchogenic cyst involves surgical excision. CASE OUTLINE: Authors present a case of a 6-year-old female patient sent by a pediatrician to a maxillofacial surgeon due to asymptomatic lump on the left side of the neck. The patient had frequent respiratory infections and respiratory obstructions. Magnetic resonance imaging (MRI) of the neck was performed and a well-circumscribed cystic formation on the left side of the neck was observed, with paratracheal location. The complete excision of the cyst was made transcervically. Histopathological findings pointed to bronchogenic cyst. CONCLUSION: Cervical bronchogenic cysts are rare congenital malformations. Considering the location, clinical findings and the radiological features, these cysts resemble other cervical lesions. Surgical treatment is important because it is both therapeutic and diagnostic. Reliable diagnosis of bronchogenic cysts is based on histopathological examination. PMID- 26259407 TI - Hand-held Echo is Not So Handy in Everyone's Hands: Misdiagnosing Congenital Septal Defects in Patients with Heart Murmurs. AB - INTRODUCTION: Echocardiography is a highly operator-dependant technique which requires adequate training and skills that are frequently not present, considering the widespread use of cardiovascular ultrasound. This could particularly be true for hand-held echo devices which made echocardiography more accessible but are frequently used by non-cardiologists and non-experts. OUTLINE OF CASES: We present a 45-year-old female and a 37-year-old male with heart murmurs due to atrial and ventricular septal defect, respectively. Congenital septal defects were undiagnosed in both patients during several outpatient examinations due to challenging image acquisition. C reful re-evaluation revealed that, depending on the scanning technique, it was possible to detect or overlook the real cause of the murmur using either hand-held or high-end echo device. CONCLUSION: Our report underlines the need of adequate knowledge and training of medical professionals performing pocket-size hand-held echocardiography, since potential misdiagnoses may not be related to limited imaging capabilities of pocket-sized echo devices only, but also to inability of insufficiently trained users to obtain good quality images and interpret them adequately. PMID- 26259408 TI - Splenic Artery Aneurysms: Two Cases of Varied Etiology, Clinical Presentation and Treatment Outcome. AB - INTRODUCTION: Splenic artery aneurysms are potentially lethal lesions. We report two illustrative cases and discuss etiology, diagnosis and treatment of these aneurysms. OUTLINE OF CASES: Both patients, age 31 and 80 years, were biparous women.The younger woman, otherwise healthy, was referred from a local hospital 3 weeks after she underwent a left subcostal laparotomy and exploration for symptomatic abdominal mass diagnosed by CT. Angiography established the diagnosis of a large, non-ruptured splenic artery aneurysm. Elective aneurysmectomy with splenectomy was performed using the approach through the upper median laparotomy and bursa omentalis. Postoperative course was uneventful. Histopathology demonstrated cystic medial necrosis with chronic dissection. The other patient, elderly woman, presented urgently with acute abdominal pain and syncope and was diagnosed by computed tomography with a huge, ruptured splenic artery aneurysm. She underwent immediate aneurysmectomy with splenectomy using the same, above mentioned approach. External pancreatic fistula and pancreatic pseudocyst complicated the postoperative course, requiring open pseudocyst drainage and cystojejunostomy. After a protracted hospitalization patient eventually recovered. The pathological diagnosis was atherosclerotic aneurysm. CONCLUSION: Splenic artery aneurysms are infrequent lesions, with varied etiology and clinical presentation. Timely diagnosis and adequate treatment prevent life threatening rupture and lessen the risk of operative morbidity and mortality. PMID- 26259409 TI - [The Laparoscopic Enucleation for Branch Duct Type Intraductal Papillary Mucinous Neoplasms Located at the Body of Pancreas: A Case Report]. AB - INTRODUCTION: Intraductal papillary mucinous neoplasms (IPMN) are among the most common cystic neoplasms of the pancreas, but they represent only 1-3% of all exocrine pancreas tumors. With the development of diagnostic possibilities the number of patients with IPMN is constantly increasing and represents approximately 20% of all surgically treated pancreatic tumors.The development of laparoscopic surgery has led to advances in the treatment of cystic tumors of the pancreas with the emergence of new surgical dilemma in the choice of surgical techniques in patients with IPMN. CASE OUTLINE: A 23-year-old patient was admitted to the hospital with non-specific symptoms of upper abdomen. Performed diagnostics indicated the existence of a tumor formation at the periphery of the pancreas, in the region of the proximal corpus, 8x5 cm in diameter. The cystic formation, wall thickness 3 mm, was filled with dense contents and injected into the tissue of the pancreas, but did not lead to an extension of the pancreatic duct. After adequate preoperative preparation the patient was operated on, when a laparoscopic enucleation of cystic tumor with coagulation and cutting off communication between the peripheral pancreatic duct and pancreatic tumors was performed by using ultrasound scissors. Histopathological analysis of the specimen indicated an IPMN of the branch duct type (BD-IPMN) with a low grade dysplasia. The line of resection was without cellular atypia. Immunohistochemical analysis showed positivity on tumor mucins (MUC-5 and MUC-2), which is typical for gastric type of BD-IPMN. Six months postoperatively the patient showed no signs of recurrence of the disease. CONCLUSION: Surgical treatment is the dominant choice for the treatment for IPMN. Although minimally invasive, laparoscopic enucleation of BD-IPMN is able to achieve an adequate level of radicality without the accompanying complications and with short postoperative recovery period. PMID- 26259410 TI - A Case of Autoimmune Cholangitis Misdiagnosed for Cholangiocarcinoma: How to Avoid Unnecessary Surgical Intervention? AB - INTRODUCTION: Autoimmune cholangitis or immunoglobulin G4-associated cholangitis (IAC) has been recently regarded as a new clinical and histopathological entity and is a part of a complex autoimmune disorder--IgG4-related systemic disease (ISD). ISD is an autoimmune disease with multi-organic involvement, characterized with IgG4-positive plasmocytic infiltration of various tissues and organs with a consequent sclerosis, which responds well to steroid therapy. Most commonly affected organs are the pancreas (autoimmune pancreatitis, [AIP]) and the common bile duct (IAC). IAC and cholangiocarcinoma (CCA) share many clinical, laboratory and imaging findings. CASE OUTLINE: We present a case of a 60-year-old male with a biliary stricture of a common bile duct, which was clinically considered as a bile duct carcinoma and treated surgically. Definite histopathological findings and immunohistochemistry revealed profound chronic inflammation, showing lymphoplasmacytic IgG-positive infiltration of a resected part of a common bile duct, highly suggestive for the diagnosis of IAC. In addition, postoperative IgG4 serum levels were also increased. CONCLUSION: It is of primary clinical importance to make a difference between IAC and CCA, in order to avoid unnecessary surgical intervention. Therefore, IAC should be considered in differential diagnosis in similar cases. PMID- 26259411 TI - [Favorable Outcome of Hepatosplenic Candidiasis in a Patient with Acute Leukemia]. AB - INTRODUCTION: Acute leukemias treatment requires strong chemotherapy. Patients that develop bone marrow aplasia become immunocompromised, thus becoming liable to bacterial and fungal infections. Fungal infections caused by Candida are frequent. Hepatosplenic candidiasis (HSC) is a frequent consequence of invasive candidiasis which is clinically presented with prolonged febrility unresponsive to antibiotics. CASE OUTLINE: A 53-year-old patient with acute myeloid leukemia was submitted to standard chemotherapy "3+7" regimen (daunoblastine 80 mg i.v. on days 1 to 3, cytarabine 2 x 170 mg i.v. during 7 days) and achieved complete remission. However, during remission he developed febrility unresponsive to antibiotics. Computerised tomography (CT) of the abdomen showed multiple hypodense lesions within the liver and spleen. Haemocultures on fungi were negative. However, seroconversion of biomarkers for invasive fungal infection (FI) (Candida and Aspergillus antigen/Ag and antibody/Ab) indicated possible HSC. Only high positivity of anti-Candida IgG antibodies, positivity of mannan and CT finding we regarded sufficient for the diagnosis and antimycotic therapy.Three months of treatment with different antimycotics were necessary for complete disappearance of both clinical symptoms and CT findings. CONCLUSION: In patients with prolonged febrile neutropenia IFI has to be strongly suspected. If imaging techniques show multiple hypodense lesions within liver and spleen, HSC has to be taken seriously into consideration. We believe that, along with CT finding, positive laboratory Candida biomarkers (mannan and IgG antibodies) should be considered sufficient for"probable HSC" and commencement of antifungal therapy, which must be long enough, i.e. until complete disappearance of clinical symptoms and CT findings are achieved. PMID- 26259412 TI - [Cardiac Manifestations in Antiphospholipid Syndrome--A Brief Review of the Literature]. AB - Antiphospholipid syndrome (APS) or Hughes syndrome represents a systemic autoimmune disorder characterized by arterial and/or venous thrombosis, multiple and recurrent fetal losses, accompanied by persistently elevated levels of antiphospholipid antibodies (aPL). This syndrome is considered primary if unassociated with any other connective tissue disease, or secondary if it appears in association with other autoimmune disorders, mainly systemic lupus erythematosus. Cardiac manifestations in APS are integral part of the syndrome. aPL are involved in the pathogenesis of pseudoinfective endocarditis (Libman Sacks) and other valvular manifestations presented as their thickening and dysfunction. Intracardiac thrombi and myxomas, pulmonary hypertension and left ventricular dysfunction are also distinguishing features of APS. On the other hand, accelerated atherosclerosis, proven in APS and also aPL mediated, is accountable for the development of coronary and peripheral artery disease. This leads to higher cardiovascular mortality rate in the population of patients with low incidence of the traditional atherosclerosis risk factors. Furthermore, recent studies implied that presence of certain aPL could be a risk factor for a specific cardiac manifestation. Bearing all this in mind, early diagnosis of cardiac manifestations, control and abolition of traditional risk factors, as well as close cardiac follow-up of APS patients, are crucial in reducing their cardiovascular mortality. PMID- 26259413 TI - [Poor Ovarian Response to Stimulation for In Vitro Fertilization]. AB - The term "poor respond (POR) patients" is used for the group of women who respond badly to usual doses of gonadotropins in in vitro fertilization (IVF) treatments; the consequence is low pregnancy rate. A consensus was reached on the minimal criteria needed to define POR. At least two of the following three features must be present: 1. advanced maternal age (40 years or more) 2. previous POR (3 or less oocytes with a conventional stimulation protocol) 3. abnormal ovarian reserve (AMH 0.5-1.1 ng/ml or AFC 5-7).The aim is to find better therapeutic options for these patients. Increased levels of day 3 follicle stimulating hormone (FSH) and estradiol (E2), as well as decreased levels of anti-Mullerian hormone (AMH) and antral follicle count (AFC), can be used to assess ovarian reserve, as indirect predictive tests. A larger number of well designed, large scale, randomized, controlled trials are needed to assess the efficacy of different management strategies for poor responders: flare up gonadotropin releasing hormone (GnRH) agonist protocols, modified long GnRH agonist mini-dose protocols, luteal initiation GnRH agonist stop protocol, pretreatment with estradiol--GnRH antagonist in luteal phase, natural cycle aspiration or natural cycle aspiration GnRH antagonist controlled, adjuvant therapy with growth hormone or dehydroepiandrosterone (DHEA). The results of up to now used protocols are unsatisfactory and stimulation of the ovulation in poor responders remains a challenge, especially when bearing in mind that in the majority of cases the patients will be menopausal in relatively short period of time. PMID- 26259414 TI - Salt Content in Ready-to-Eat Food and Bottled Spring and Mineral Water Retailed in Novi Sad. AB - INTRODUCTION: Salt intake above 5 g/person/day is a strong independent risk factor for hypertension, stroke and cardiovascular diseases. Published studies indicate that the main source of salt in human diet is processed ready-to-eat food, contributing with 65-85% to daily salt intake. OBJECTIVE: The aim of this paper was to present data on salt content of ready-to-eat food retailed in Novi Sad, Serbia, and contribution of the salt contained in 100 g of food to the recommended daily intake of salt for healthy and persons with cardiovascular disease (CVD) risk. METHODS: In 1,069 samples of ready-to-eat food, salt (sodium chloride) content was calculated based on chloride ion determined by titrimetric method, while in 54 samples of bottled water sodium content was determined using flame-photometry. Food items in each food group were categorized as low, medium or high salt. Average salt content of each food group was expressed as a percentage of recommended daily intake for healthy and for persons with CVD risk. RESULTS: Average salt content (g/100 g) ranged from 0.36 +/- 0.48 (breakfast cereals) to 2.32 +/- 1.02 (grilled meat). The vast majority of the samples of sandwiches (91.7%), pizza (80.7%), salami (73.9%), sausages (72.9%), grilled meat (70.0%) and hard cheese (69.6%) had a high salt profile. Average amount of salt contained in 100 g of food participated with levels ranging from 7.2% (breakfast cereals) to 46.4% (grilled meat) and from 9.6% to 61.8% in the recommended daily intake for healthy adult and person with CVD risk, respectively. Average sodium content in 100 ml of bottled spring and mineral water was 0.33 +/- 0.30 mg and 33 +/- 44 mg, respectively. CONCLUSION: Ready-to-eat food retailed in Novi Sad has high hidden salt content, which could be considered as an important contributor to relatively high salt consumption of its inhabitants. PMID- 26259415 TI - Changes Needed in the Classification of Anxiety Disorders in Childhood: Options for ICD-11. AB - Considering the intensive preparation of the 11th revision of the International Classification of Diseases (ICD-11), we discussed the justification of the existing classification of emotional disorders with onset specific to childhood. This paper presents the citations from the ICD-10 (F93 block) and the authors' comments as a critical review of the justification of further existence of emotional disorders with onset specific to childhood as a separate block in ICD 11 classification. We concluded that the block F93 is insufficiently defined and should be completely changed or removed from the ICD-11 classification. Additionally, the specificities of the clinical picture of anxiety disorders in children should be adequately described within the future category of anxiety and phobic disorders by giving an explicit set of instructions for identifying clinical manifestations which vary by age. PMID- 26259416 TI - Rickettsial Diseases in India: Not as Uncommon as Believed. PMID- 26259417 TI - Stroke-Transient Cerebral Ischaemic Attacks (TIAs) A Medical Emergency Preventable and Treatable. AB - TIA is a serious condition and a medical emergency requiring immediate evaluation and treatment to prevent a stroke. Confirmation of diagnosis is vital. Medical conditions like hypoglycaemia, migraine etc which mimic TIA should be identified. TIA syndrome in carotid territory needs special evaluation by Duplex sonography to detect significant stenosis (>70%) near bifurcation. Recurrent TIA in the same territory leaves neuro deficit and this needs prevention by appropriate therapy (platelet antiaggregants, anticoagulants, surgical intervention). An algorithm listing initial workup for TIA is shown in Figure 1. Associated risk factors (e.g. high blood pressure, tobacco use, uncontrolled diabetes mellitus, high cholesterol level and obesity etc) need special emphasis. Lifestyle modification and lack of physical exercise cannot be ignored. In high risk group where TIA lasts longer than 10 minutes with significant neuro deficit in elderly subjects having diabetes or hypertension will need special attention and treatment. Diagnostic tests should include cardiovascular evaluation and ultrasound scanning of carotid arteries. Special neuroimaging tests like CT/MRI and CTA/MRA to visualize cerebral vasculature and detect asymptomatic lesions are helpful in planning long term management and prevention of stroke. PMID- 26259418 TI - Clinical Manifestations and Complications of Scrub Typhus : A Hospital Based Study from North Eastern India. AB - OBJECTIVES: To study the different clinical manifestations and complications associated with scrub typhus. METHODS: A hospital based prospective observational study of patients of acute febrile illness above 18 years age. Diagnosis was based on clinical and serological data. RESULTS: A total of 61 patients were diagnosed with scrub typhus, with males more than females. Most (42.37%) belonged to 18 to 30 years age group. Fever with headache was the commonest presentation (94.91%). Multiorgan dysfunction syndrome was the most common complication (16.94%). The mortality rate was 8.47%. CONCLUSION: The study reveals the clinical manifestations and complications of a well known mite borne disease in the state of Meghalaya. The varied presentations and high mortality requires a high index of suspicion. The study highlights the clustering of cases during the months of September to November. PMID- 26259419 TI - Analysis of Two Outbreaks of Scrub Typhus in Rajasthan: A Clinico-epidemiological Study. AB - AIMS AND OBJECTIVES: To describe the diversity of clinical manifestations, laboratory findings and outcome of scrub typhus in hospitalised patients of SMS Hospital, Jaipur during 2012 and 2013. MATERIAL AND METHODS: All the cases of febrile illness with thrombocytopenia diagnosed as scrub typhus were analysed. Diagnosis was made by ELISA based IgM serology. OBSERVATIONS AND RESULTS: A total of 125 patients were studied. All of them presented with fever; the other major symptoms were headache, cough, dyspnoea and myalgias. On examination, patients had hepatosplenomegaly, lymphadenopathy and eschar. On investigation elevated SGOT, SGPT with normal or elevated bilirubin levels were the most common findings. Other laboratory findings were thrombocytopenia and deranged renal function tests. Most common X-ray finding observed in these patients was bilateral lung infiltrates. Other complications were MODS, ARDS, hypotension and meningoencephalitis. Majority responded to doxycycline. CONCLUSION: Scrub typhus though prevalent is under-reported in our country. It should be considered as an important differential diagnosis in a febrile patient with thrombocytopenia, deranged liver or renal functions, and B/L chest opacities. Early diagnosis and appropriate treatment is rewarding and prevents morbidity and mortality. PMID- 26259420 TI - Therapeutic Effects of Oral Nutritional Supplements during Haemodialysis: Physician's Experience. AB - OBJECTIVES: To evaluate the effects of predialytic oral nutritional supplementation in chronic kidney disease (CKD) patients on maintenance haemodialysis (MHD). METHODS: NEPRO HP was provided to 77 CKD patients on maintenance haemodialysis (MHD) over 3 months. Efficacy parameters were improvement in albumin levels, weight and haemoglobin levels; safety parameters were serum potassium and phosphorus values; other parameters were SGA and MIS scores. RESULTS: Mean serum albumin values showed a statistically significant increase. There was a statistically significant improvement in the mean body weight and haemoglobin of the patients in the second and third months of treatment. Serum phosphorus and potassium levels did not change in a statistically significant manner. There was improvement in nourishment status as detected by MIS and SGA scores. Two patients expired during the course of the study. CONCLUSION: Predialytic oral supplementation with NEPRO HP improves nutritional status of CKD patients on MHD. PMID- 26259421 TI - Sudden Cardiac Death in India: A Growing Concern. AB - The incidence of sudden cardiac death (SCD) is based on studies from North America and Western Europe with very few countries in Asia having conducted robust studies evaluating the occurrence of SCD. This paper reviewed published data on SCD, with a focus on India. In recent years, varying methods of assessment such as verbal autopsies, questionnaires, and quantification of surrogate endpoints such as cardiovascular disease profiles have been used to estimate the incidence of SCD. These studies have shown that the incidence of SCD is on the rise, especially in the urban regions, which may be largely attributed to the increase in prevalence of coronary artery disease, diabetes and hypertension in India. These studies have shown that the risk stratification and management approach for SCD are conspicuously varied and there is a need for establishing a systematic approach for estimating the incidence and risk factors of SCD in India. PMID- 26259422 TI - A Case of Achalasia Cardia. PMID- 26259423 TI - Hereditary HaemorrhagicTelangiectasia--A Rare Cause of Severe Anaemia. AB - Hereditary Haemorrhagic Telangiectasia also known as Osler-Rendu-Weber disease is a rare autosomal dominant disorder affecting small vessels of skin and mucosa, usually misdiagnosed because of its non specific symptomatology. This disease usually presents as epistaxis, gastrointestinal bleeding and visceral arteriovenous malformations. Although the epistaxis and gastrointestinal blood loss can result in anaemia, patients with hereditary haemorrhagic telangiectasia rarely presents as severe anaemia. Herein, we report a case of a 60 year-old man with severe anaemia resulting in congestive cardiac failure who ultimately was diagnosed as hereditary haemorrhagic telangiectasia with recurrent epistaxis as a cause of his severe anaemia. PMID- 26259424 TI - A Rare Case of Vanishing Lung Syndrome. AB - Vanishing lung syndrome (VLS) is a rare radiological syndrome in which the lungs appear to be disappearing on X-ray. It is a chronic, progressive condition usually affecting young male smokers and is characterised by giant emphysematous bullae, which commonly develop in the upper lobes. We describe here a rare case of 60-year-old male patient who had a history of chronic smoking for 30 years. He had been admitted in the hospital multiple times due to spontaneous pneumothorax, type 2 respiratory failure and infective exacerbations. He was earlier diagnosed having chronic obstructive pulmonary disease (COPD) with predominant emphysema on the basis of his history and chest X-ray findings. Eventually, his CT chest revealed the diagnosis of giant bullous disease/vanishing lung syndrome. He had been surviving with his little lung tissue for about 10 years. No such case has been reported in the literature so far. He was attended last on 12th October, 2009 in medical outdoor of Christian Medical College and Hospital, Ludhiana by the first three authors. Thereafter, the patient was not traceable. PMID- 26259425 TI - Systemic Sclerosis Sine Scleroderma. AB - Systemic sclerosis sine scleroderma is a rare form of limited systemic sclerosis. These patients are without skin involvement, but do not differ in its clinical or laboratory features and prognosis from classical systemic sclerosis. In the absence of cutaneous signs/symptoms, its diagnosis is delayed leading to significant morbidity and mortality. We report a case of sixty year old female who presented to us with dyspnoea on exertion and Raynaud's phenomenon. She was investigated and was found to have this disorder with pulmonary artery hypertension. PMID- 26259426 TI - Hepatopulmonary Syndrome, Severe Cyanosis and Marfanoid Habitus. AB - We report the case of a 17-year-old male with Marfanoid habitus who presented with deep cyanosis, haematemesis, dyspnoea and platypnoea. He had oesophageal varices, indicating portal hypertension, with mildly deranged liver function. His arterial blood gas (ABG) revealed hypoxia and orthodeoxia. Contrast-enhanced echocardiography with agitated saline and a 99m Technetium macro-aggregated albumin perfusion lung scan confirmed intrapulmonary shunting. Pulmonary angiogram showed multiple, small diffuse pulmonary arteriovenous fistulae scattered all over the lungs and predominantly in the bases of the lungs. Based on these results and the clinical background a diagnosis of hepatopulmonary syndrome with Marfanoid habitus was made. Patient was treated conservatively as he was not prepared for liver transplantation. PMID- 26259427 TI - A Case Report of Tuberous Sclerosis in Two Generations. AB - Tuberous sclerosis complex [TSC] is a genetic multisystem disorder characterised by the growth of numerous hamartomas in several organs including the brain, heart, skin, eyes, kidney, lung and liver. The affected genes are TSC1 and TSC2 encoding hamartin and tuberin respectively. TSC has a wide range of severity and some people with this condition will only be mildly affected. At present it is impossible to accurately predict who will remain only mildly affected and who will be more severely affected by TSC. Even members of the same family can be affected differently. Many family members show signs of being carriers of the genes for the disease when carefully examined. This article reports a family with documented Tuberous sclerosis in two generations involving three members which is a rare entity. PMID- 26259428 TI - Friedrich Wegener. PMID- 26259429 TI - Dr. N Kochupillai. PMID- 26259430 TI - Shibasaburo Kitasato--Samurai Bacteriologist. PMID- 26259431 TI - Science of Exercise: Ancient Indian Origin. PMID- 26259432 TI - Reply from Author. PMID- 26259433 TI - The Patient's Alarm Clock in STEMI. PMID- 26259434 TI - Scrub Typhus--A Re-Emerging Infection. PMID- 26259435 TI - [Profile distribution and storage of soil organic carbon in a black soil as affected by land use types]. AB - Taking soils in a long-term experimental field over 29 years with different land uses types, including arable land, bare land, grassland and larch forest land as test materials, the distribution and storage of soil organic carbon (SOC) in the profile (0-200 cm) in typical black soil (Mollisol) region of China were investigated. The results showed that the most significant differences in SOC content occurred in the 0-10 cm surface soil layer among all soils with the order of grassland > arable land > larch forest land > bare land. SOC contents at 10 120 cm depth were lower in arable land as compared with the other land use types. Compared with arable land, grassland could improve SOC content obviously. SOC content down to a depth of 60 cm in grassland was significantly higher than that in arable land. The content of SOC at 0-10 cm in bare land was significantly lower than that in arable land. Although there were no significant differences in SOC content at 0-20 cm depth between larch forestland and arable land, the SOC contents at 20-140 cm depth were generally higher in larch forestland than that in arable land. In general, SOC content showed a significantly negative relationship with soil pH, bulk density, silt and clay content and an even stronger significantly positive relationship with soil total N content and sand content. The SOC storage in arable land at 0-200 cm depth was significantly lower than that in the other three land use types, which was 13.6%, 11.4% and 10.9% lower than in grassland, bare land and larch forest land, respectively. Therefore, the arable land of black soil has a great potential for sequestering C in soil and improving environmental quality. PMID- 26259436 TI - [Spatiotemporal pattern of carbon sources and sinks in Yangtze River Delta region, China]. AB - Yangtze River Delta region is the world's sixth and China's largest urban agglomeration. Its rapid and massive urbanization has also caused a series of ecological and environmental impacts. This paper accounted the inventory of carbon sources and sinks in Yangtze River Delta region during 1995-2010 and analyzed their spatiotemporal patterns. It was found that the carbon sinks increased by 9.43 million tons from 1995 to 2010, in which forest ecosystem net production in Zhejiang Province was the largest contributor. The "grain for green" policy implemented since 2003 in China played a significant role in increasing the forest area and the carbon sinks. The carbon sources increased by 327 million tons, and energy consumption and industrial processes based emissions accounted for 96% of total carbon sources in 2010. Due to the large share of manufacturing and heavy industries in economy and their dependence on the high carbon intensity energy, either the amount or the growth speed of carbon emissions in Jiangsu Province was the top one in the whole region. Moreover, because the growth speed of net carbon emissions that occurred upon the built-up land was much faster than the sprawl speed of urban built-up land, the net carbon emission intensity kept increasing in the whole region, in which Jiangsu Province demonstrated the fastest increase. PMID- 26259437 TI - [Effects of different land-use types on soil organic carbon and its prediction in the mountainous areas in the middle reaches of Lancang River]. AB - Based on the analysis of 210 surface soil samples (0-20 cm) according to field investigation in 2011, soil organic carbon (SOC) content and its distribution under four different land-use types in the middle reaches of Lancang River were studied. Combining with the correlation analysis, relationships among SOC content, land-use type, topographical factors and NDVI were revealed. Furthermore, multiple linear regression and Kriging method were used to predict the SOC contents distribution in the mountainous areas in the middle reaches of Lancang River. The results exhibited that the rank order of SOC content under the four land-use types was forestland > scrubland > grassland > farmland. The important factors influencing the SOC content were land-use type, aspect, slope and curvature. Comparing the accuracy of these two models, we found that the multiple regression model performed better than geo-statistics in prediction of the SOC content in the mountainous region. PMID- 26259438 TI - [Impact of changes in land use and climate on the runoff in Liuxihe Watershed based on SWAT model]. AB - SWAT model, an extensively used distributed hydrological model, was used to quantitatively analyze the influences of changes in land use and climate on the runoff at watershed scale. Liuxihe Watershed' s SWAT model was established and three scenarios were set. The calibration and validation at three hydrological stations of Wenquan, Taipingchang and Nangang showed that the three factors of Wenquan station just only reached the standard in validated period, and the other two stations had relative error (RE) < 15%, correlation coefficient (R2) > 0.8 and Nash-Sutcliffe efficiency valve (Ens) > 0.75, suggesting that SWAT model was appropriate for simulating runoff response to land use change and climate variability in Liuxihe watershed. According to the integrated scenario simulation, the annual runoff increased by 11.23 m3 x s(-1) from 2001 to 2010 compared with the baseline period from 1991 to 2000, among which, the land use change caused an annual runoff reduction of 0.62 m3 x s(-1), whereas climate variability caused an annual runoff increase of 11.85 m3 x s(-1). Apparently, the impact of climate variability was stronger than that of land use change. On the other hand, the scenario simulation of extreme land use showed that compared with the land use in 2000, the annual runoff of the farmland scenario and the grassland scenario increased by 2.7% and 0.5% respectively, while that of the forest land scenario were reduced by 0.7%, which suggested that forest land had an ability of diversion closure. Furthermore, the scenario simulation of climatic variability indicated that the change of river runoff correlated positively with precipitation change (increase of 11.6% in annual runoff with increase of 10% in annual precipitation) , but negatively with air temperature change (reduction of 0.8% in annual runoff with increase of 1 degrees C in annual mean air temperature), which showed that the impact of precipitation variability was stronger than that of air temperature change. Therefore, in face of climate variability, we need to pay attention to strong rainfall forecasts, optimization of land use structure and spatial distribution, which could reduce the negative hydrological effects (such as floods) induced by climate change. PMID- 26259439 TI - [Comparison on the methods for spatial interpolation of the annual average precipitation in the Loess Plateau region]. AB - Based on 57 years (1957-2013) daily precipitation datasets of the 85 meteorological stations in the Loess Plateau region, different spatial interpolation methods, including ordinary kriging (OK), inverse distance weighting (IDW) and radial-based function (RBF), were conducted to analyze the spatial variation of annual average precipitation regionally. Meanwhile, the mean absolute error (MAE), the root mean square error (RMSE), the accuracy (AC) and the Pearson correlation coefficient (R) were compared among the interpolation results in order to quantify the effects of different interpolation methods on spatial variation of the annual average precipitation. The results showed that the Moran's I index was 0.67 for the 57 years annual average precipitation in the Loess Plateau region. Meteorological stations exhibited strong spatial correlation. The validation results of the 63 training stations and 22 test stations indicated that there were significant correlations between the training and test values among different interpolation methods. However, the RMSE (IDW = 51.49, RBF = 43.79) and MAE (IDW = 38.98, RBF = 34.61) of the IDW and the RBF showed higher values than the OK. In addition, the comparison of the four semi variagram models (Circular, Spherical, Exponential and Gaussian) for the OK indicated that the circular model had the lowest MAE (32.34) and the highest accuracy (0.976), while the MAE of the exponential model was the highest (33.24). In conclusion, comparing the validation between the training data and test results of the different spatial interpolation methods, the circular model of the OK method was the best one for obtaining accurate spatial interpolation of annual average precipitation in the Loess Plateau region. PMID- 26259440 TI - [Soil infiltration of snowmelt water in the southern Gurbantunggut Desert, Xinjiang, China]. AB - Soil infiltration of snow-melt water is an important income item of water balance in arid desert. The soil water content in west slope, east slope and interdune of sand dune in the southern Gurbantunggut Desert was monitored before snowfall and after snow melting during the winters of 2012-2013 and 2013-2014. According to the principle of water balance, soil infiltration of snow-melt in the west slope, east slope, interdune and landscape scale was calculated, and compared with the results measured by cylinder method. The results showed that the soil moisture recharge from unfrozen layer of unsaturated soil to surface frozen soil was negligible because the soil moisture content before snowfall was lower, soil infiltration of snow-melt water was the main source of soil water of shallow soil, phreatic water did not evaporate during freezing period, and did not get recharge after the snow melting. Snowmelt water in the west slope, east slope, interdune and landscape scale were 20-43, 27-43, 32-45, 26-45 mm, respectively. PMID- 26259441 TI - [Using a modified remote sensing imagery for interpreting changes in cultivated saline-alkali land]. AB - This paper developed a new interpretation symbol system for grading and classifying saline-alkali land, using Huanghua, a cosatal city in Hebei Province as a case. The system was developed by inverting remote sensing images from 1992 to 2011 based on site investigation, plant cover characteristics and features of remote sensing images. Combining this interpretation symbol system with supervising classification method, the information on arable land was obtained for the coastal saline-alkali ecosystem of Huanghua City, and the saline-alkali land area, changes in intensity of salinity-alkalinity and spatial distribution from 1992 to 2011 were analyzed. The results showed that salinization of arable land in Huanghua City alleviated from 1992 to 2011. The severely and moderately saline-alkali land area decreased in 2011 compared with 1992, while the non/slightly saline land area increased. The moderately saline-alkali land in southeast transformed to non/slightly saline-alkaline, while the severely saline alkali land in west of the city far from the coastal zone became moderately saline-alkaline. The center of gravity (CG) of severely and non/slightly saline alkali land moved closer the coastline, while that of the moderately saline alkali land moved from southwest coastal line to northwest. Factors influencing changes in arable land within the saline-alkali ecosystem of Huanghua City were climate, hydrology and human activities. PMID- 26259442 TI - [Urban ecosystem services: A review]. AB - Maintaining and improving ecosystem services in urban areas and human well-being are essential for sustainable development and therefore constitute an important topic in urban ecology. Here we reviewed studies on ecosystem services in urban areas. Based on the concept and classification of urban ecosystem services, we summarized characteristics of urban ecosystem services, including the human domination, high demand of ecosystem services in urban areas, spatial heterogeneity and temporal dynamics of ecosystem services supply and demand in urban areas, multi-services of urban green infrastructures, the socio-economic dimension of ecosystem services supply and ecosystem disservices in urban areas. Among different urban ecosystem services, the regulating service and cultural service are particularly indispensable to benefit human health. We pointed out that tradeoffs among different types of ecosystem services mostly occur between supportive service and cultural service, as well as regulating service and cultural service. In particular, we emphasized the relationship between landscape design (i.e. green infrastructure) and ecosystem services supply. Finally, we discussed current gaps to link urban ecosystem services studies to landscape design and management and pointed out several directions for future research in urban ecosystem services. PMID- 26259443 TI - [Vegetation landscape health assessment in Changshan Archipelago, North Yellow Sea]. AB - Island vegetation is an important component of island ecosystem. Multi-targets of island ecosystem health integrated with landscape ecology theory were employed to construct the index system for island vegetation health assessment in terms of landscape vigor, landscape stressing intensity and landscape stability. The Changshan Archipelago in the North Yellow Sea was chosen as a case to apply the island vegetation health assessment index system. The results showed that the overall vegetation health status in Changshan Archipelago was good and had a big island variation. The vegetation health index for Haiyang Island and Zhangzi Island was above 0.80, belonging to first eco-health level area, whereas that for Dachangshan Island, Xiaochangshan Island and Dawangjia Island ranged from 0.70 to 0.80, which could be categorized as the second eco-health level area. Guanglu Island and Shichen Island could be termed as the third eco-health level area with the vegetation health index below 0.70. The distance of island to mainland, area of island together with industrial structure were the main driving forces for the variation of vegetation landscape heath between different islands. PMID- 26259444 TI - [Measuring water ecological carrying capacity with the ecosystem-service-based ecological footprint (ESEF) method: Theory, models and application]. AB - Integrated watershed management based on aquatic ecosystems has been increasingly acknowledged. Such a change in the philosophy of water environment management requires recognizing the carrying capacity of aquatic ecosystems for human society from a more general perspective. The concept of the water ecological carrying capacity is therefore put forward, which considers both water resources and water environment, connects socio-economic development to aquatic ecosystems and provides strong support for integrated watershed management. In this paper, the authors proposed an ESEF-based measure of water ecological carrying capacity and constructed ESEF-based models of water ecological footprint and capacity, aiming to evaluate water ecological carrying capacity with footprint methods. A regional model of Taihu Lake Basin was constructed and applied to evaluate the water ecological carrying capacity in Changzhou City which located in the upper reaches of the basin. Results showed that human demand for water ecosystem services in this city had exceeded the supply capacity of local aquatic ecosystems and the significant gap between demand and supply had jeopardized the sustainability of local aquatic ecosystems. Considering aqua-product provision, water supply and pollutant absorption in an integrated way, the scale of population and economy aquatic ecosystems in Changzhou could bear only 54% of the current status. PMID- 26259445 TI - [Ecological footprint of farmers and herdsmen in Tibet Autonomous Region, China]. AB - Based on relevant statistical yearbook and with an integrated method, the ecological footprint and ecological carrying capacity of farmers and herdsmen during the period from 2000 to 2012 in Tibet Autonomous Region, China were studied. The results showed that the ecological status of farmers and herdsmen were in a surplus state during the study period, but the surplus amount exhibited a decreasing tendency. The ecological capacity decreased from 7.49 hm2 in 2000 to 6.35 hm2 in 2012, with a decrease of 15.3%, while the ecological footprint increased gradually from 1.03 hm2 in 2000 to 1.26 hm2 in 2012. PMID- 26259446 TI - [Socio-hydrology: A review]. AB - Socio-hydrology is an interdiscipline of hydrology, nature, society and humanity. It mainly explores the two-way feedbacks of coupled human-water system and its dynamic mechanism of co-evolution, and makes efforts to solve the issues that human faces today such as sustainable utilization of water resources. Starting from the background, formation process, and fundamental concept of socio hydrology, this paper summarized the features of socio-hydrology. The main research content of socio-hydrology was reduced to three aspects: The tradeoff in coupled human-water system, interests in water resources management and virtual water research in coupled human-water system. And its differences as well as relations with traditional hydrology, eco-hydrology and hydro-sociology were dwelled on. Finally, with hope to promote the development of socio-hydrology researches in China, the paper made prospects for the development of the subject from following aspects: Completing academic content and deepening quantitative research, focusing on scale studies of socio-hydrology, fusing socio-hydrology and eco-hydrology. PMID- 26259447 TI - [Influence of mulching management on the relationships between foliar non structural carbohydrates and N, P concentrations in Phyllostachys violascens stand]. AB - To understand the physiological adaptive mechanism of Phyllostachys violascens to intensive mulching management, the effect of mulching management (CK, 1, 3 and 6 years) on the concentrations and ratios of non-structural carbohydrates (NSC), nitrogen (N) and phosphorus (P) in bamboo foliage, and their stoichiometry was investigated. The results showed the concentrations of NSC and soluble sugar increased, while the starch content and N/P decreased markedly in bamboo stand with 1-year mulching, compared to CK stand, which suggested the N limitation to bamboo growth was strengthened. Foliar soluble sugar content decreased significantly, while the starch content increased dramatically, and the NSC content by per unit mass of N and P reached the maximum in the bamboo stand with 3-year mulching, compared to all other treatments. Foliar NSC and soluble sugar contents decreased significantly, while foliar starch content and N/P increased dramatically in the stand with 6-year mulching, which suggested the P limitation to bamboo growth was strengthened. Foliar NSC content was positively correlated with N and P concentrations in a short-term mulching management stand (<= 3 years), while showed negative relationship with N/P. The foliar starch content in the stand with 6-year mulching was negatively correlated with N and P contents, while was positively correlated with N/P. The results indicated that short-term mulching management accelerated the accumulation of soluble sugar and decomposition of starch in foliage, thus the growth and activity of Ph. violascens was enhanced greatly. Long-term mulching management promoted the starch accumulation, which led to the transition from N limitation to P limitation for bamboo growth. In summary, long-term (6 years) mulching management caused the decrease of growth and activity of Ph. violascens dramatically, thus enhancing the bamboo stand degradation. The utilization efficiency of N and P reached the highest in the stand with 3-year mulching, which implied 3-year was the best suitable period for intensive mulching management for maintaining bamboo stand quality. PMID- 26259448 TI - [Relationships between understory vegetation coverage and environmental factors in Pinus massoniana plantations from aerial seeding]. AB - The relationships between understory vegetation coverage and environmental factors in Pinus massoniana plantations from aerial seeding were studied by using principal component analysis, redundancy analysis and variation partitioning. The selected environmental factors in total explained 74.2% variation of the understory vegetation coverage. At low altitude, stand characteristics were the key factor to influence the understory vegetation coverage. Stand characteristics, soil property and topographic factor were respectively explained 55.0% (including 29.1% for separateness and 25.9% for interaction with other factors), 38. 9% (including 12.1% for separateness and 26.8% for interaction with other factors) and 9.0% (including 5.6% for separateness and 3.4% for interaction with other factors) of the total variation. Average diameter at breast height and canopy density affected mostly and positively correlated with the coverage of bryophyta, graminoid and shurb groups at significant level. Noncapillary porosity and soil water content showed a highly significant positive correlation to dicranopteris coverage, whereas average diameter at breast height, canopy density, soil nutrients and enzyme activity significantly negatively correlated with it. The coverage of graminoid, bryophyta and shurb groups showed the positive correlations, which indicated the three groups could promote each other, while the dicranopteris coverage had significant negative correlation with the three groups mentioned above. PMID- 26259450 TI - [Light response characteristics of photosynthesis and model comparison of Distylium chinense in different flooding durations]. AB - The light responses of photosynthesis of two-year-old Distytum chinense seedlings subjected to a simulated reservoir flooding environment in autumn and winter seasons were measured by using a Li-6400 XT portable photosynthesis system, and the light response curves were fitted and analyzed by three models of the rectangular hyperbola, non-rectangular hyperbola and modified rectangular hyperbola to investigate the applicability of different light response models for the D. chinense in different flooding durations and the adaption regulation of light response parameters to flooding stress. The results showed that the fitting effect of the non-rectangular hyperbola model for light response process of D. chinense under normal growth condition and under short-term flooding (15 days of flooding) was better than that of the other two models, while the fitting effect of the modified rectangular hyperbola model for light response process of D. chinense under longer-term flooding (30, 45 and 60 days of flooding) was better than that of the other two models. The modified rectangular hyperbola model gave the best fitted results of light compensation point (LCP) , maximum net photosynthetic rate (P(n max)) and light saturation point (LSP), and the non rectangular hyperbola model gave the best fitted result of dark respiration rate (R(d)). The apparent quantum yield (Phi), P(n max) and LSP of D. chinense gradually decreased, and the LCP and R(d) of D. chinense gradually increased in early flooding (30 days), but D. chinense gradually produced adaptability for flooding as the flooding duration continued to increase, and various physiological indexes were gradually stabilized. Thus, this species has adaptability to some degree to the flooding environment. PMID- 26259449 TI - [Decomposition dynamics of leaf litter in logging residue of a secondary Castanopsis carlesii plantation and its chemical composition changes]. AB - A field experiment was conducted to understand the decomposition rates and chemical composition changes of leaf litter in logging residues of a 35-year-old secondary Castanopsis carlesii plantation over a period of one year. Mass loss rate of leaf litter showed an exponential decrease with time from May 2012 to April 2013, with a total 80% loss of initial dry mass. Net potassium (K) release was observed during this period, with only 5% of initial K remained. Nitrogen ( N) featured a pattern of accumulation at the early stage and release later, while phosphorus (P) exhibited a sequence of release, accumulation, and release. The remaining of N and P were 19% and 16% of their initial mass, respectively. The release rate was highest for K and the lowest for N. Decomposition of lignin indicated a trend of release-accumulation-release from May 2012 to October 2012, with no further significant change from November 2012 to the end of the experiment. The concentration of cellulose nearly unchanged during the experiment. The N/P rate increased with decomposition, ranging from 18.6 to 21.1. The lignin/N rate fluctuated greatly at the early stage and then almost stabilized thereafter. PMID- 26259451 TI - [Demography and spectrum analysis of Juglans cathayensis populations at different altitudes in the west Tianshan valley in Xinjiang, China]. AB - Juglans cathayensis is an endangered plant species and listed as a class II protected species of the national government of China. In order to grasp the current state of J. cathayensis populations and predict the population dynamics in the future, a large-sample investigation was conducted in the sample plots along different altitude gradients in four valleys in J. cathayensis conservation area. According to the diameter at breast height (DBH) class of the trees, the age class structures of the populations were analyzed, and static life tables for J. cathayensis populations in different habitats along the altitude gradient was constructed by smoothing out technique, and comparative fluctuations cycles of the populations in different habitats were carried out by spectral analysis. The results showed that DBH decreased gradually with the increasing altitude. The population was composed of 19 age classes in the low-altitude habitat (1241 - 1380 m) with the maximum DBH of 91.7 cm, 18 age classes in the middle-altitude habitat (1381 - 1490 m) with the maximum DBH of 82.8 cm, and 13 age classes in the high-altitude habitat (1491 - 1670 m) with the maximum DBH of 58.9 cm. Life expectancies of J. cathayensis populations were fluctuant for the same age class at different altitudes and for different age classes at the same altitude. In the three altitude-different habitats, the survival curves of the populations trended toward Deevey- II type and the age structures of the populations were expanding. The curves of mortality showed three peaks, and the mortality rates of 9 age classes at 1241 - 1380 m and 1491 - 1670 m above sea levels were the highest, being 55.9% and 89.8%, respectively, and the mortality rate of 12 age classes at 1381 - 1490 m above sea level was the highest (79.4%). The population dynamics was significantly affected by the fundamental wave of biological characteristic throughout the life cycle of J. cathayensis population, and small cycles of multi harmonic superposition with large cycles were presented. J. cathayensis is a long lifespan tree and a major dominant species in this conservation area. The natural regeneration of its current populations is good. If not strong anthropogenic disturbances or severe natural disasters, J. cathayensis would maintain the dominant position in the community. PMID- 26259452 TI - [Dynamics of carbon and nitrogen storage of Cupressus chengiana plantations in the arid valley of Minjiang River, Southwest China]. AB - The carbon and nitrogen storage and distribution patterns of Cupressus chengiana plantation ecosystems with different stand ages in the arid valley of Minjiang River were studied. The results showed that carbon contents in different organs of C. chengiana were relatively stable, while nitrogen contents were closely related to different organs, and soil organic carbon and nitrogen contents increased with the stand age. Carbon and nitrogen storage in vegetation layer, soil layer, and the whole ecosystem of the plantation increased with the stand age. The values of total carbon storage in the 13-, 11-, 8-, 6- and 4-year-old C. chengiana plantation ecosystems were 190.90, 165.91, 144.57, 119.44, and 113.49 t x hm(-2), and the values of total nitrogen storage were 19.09, 17.97, 13.82, 13.42, and 12.26 t x hm(-2), respectively. Most of carbon and nitrogen were stored in the 0-60 cm soil layer in the plantation ecosystems and occupied 92.8% and 98.8%, respectively, and the amounts of carbon and nitrogen stored in the top 0-20 cm soil layer, accounted for 54.4% and 48.9% of those in the 0-60 cm soil layer, respectively. Difference in distribution of carbon and nitrogen storage was observed in the vegetation layer. The percentage of carbon storage in tree layer (3.7%) were higher than that in understory vegetation (3.5%), while the percentage of nitrogen storage in tree layer (0.5%) was lower than that in understory (0.7%). The carbon and nitrogen storage and distribution patterns in the plantations varied obviously with the stand age, and the plantation ecosystems at these age stages could accumulate organic carbon and nitrogen continuously. PMID- 26259453 TI - [Seasonal dynamics of soil net nitrogen mineralization under moss crust in Shapotou region, northern China]. AB - Seasonal variations of soil inorganic nitrogen (N) pool and net N transformation rate in moss-covered soil and in the bare soil were comparatively observed by incubating intact soil columns with parafilm capping in the field in a natural vegetation area of Shapotou, southeastern fringe of the Tengger Desert. We found pronounced seasonal variations in soil available N content and net N transformation rate in both moss-covered soil and bare soil, with significant differences among different months. In non-growing season, soil available N content and net N transformation rate were significantly higher in March and October than in other months. Furthermore, immobilization was the dominant form of N mineralization, and no significant difference in net soil N mineralization rate was found between the two sampling soils. In growing season, soil available N content and net N transformation rate markedly increased and reached their peak values during June to August (17.18 mg x kg(-1) and 0.11 mg x kg(-1) x d(-1), respectively). Both soil net nitrification and N mineralization rates in moss covered soil were significantly higher than in bare soil. Soil ammonium and nitrate N content in April and May were higher in moss-covered soil (2.66 and 3.16 mg x kg(-1), respectively) than in bare soil (1.02 and 2.37 mg x kg(-1), respectively); while the tendency was the converse in June and September, with 7.01 mg x kg(-1) for soil ammonium content and 7.40 mg x kg(-1) for nitrate N content in bare soil, and they were 6.39 and 6.36 mg x kg(-1) in moss-covered soil, respectively. Therefore, the existence and succession of moss crusts could be considered as one of the important biological factors affecting soil N cycling through regulating soil available N content and promoting soil N mineralization process. PMID- 26259454 TI - [Phylogenetic diversity of airborne microbes in Qingdao downtown in autumn]. AB - To determine the community structure of airborne microbes in Qingdao downtown in autumn, the airborne bacteria and fungi were collected by the KC-6120 air sampler and analyzed using the 16S/18S rDNA gene clone library method. Phylogenetic analysis of airborne bacteria showed that they belonged to six major phylogenetic groups: Proteobacteria (78. 8%), Firmicutes (14.6%), Actinobacteria (4.0%), Planctomycetes (1.3%), Cyanobacteria (0.7%), and Deinococcus-Thermus (0.7%). The dominant genera of airborne bacteria included Acinetobacter (39.7%), Staphylococcus (11.3%), Sphingomonas (8.6%), Paracoccus (6.0%) and Massilia (5.3%). The main types of airborne fungi were Ascomycota (97.5%) and Basidiomycota (2.5%). Dominant genera of airborne fungi included Pyrenophora (76.5%), Xylaria (13.6%) and Exophiala (2.5%). The pathogens or conditioned pathogens, such as Acinetobacter, Staphylococcus, or Sphingomonas were detected in the airborne bacteria, whereas certain kinds of fungi, such as P. graminea, X. hypoxylon and Zasmidium angulare that could cause a variety of crop diseases were also detected. PMID- 26259455 TI - [Influence of different types of surface on the diversity of soil fauna in Beijing Olympic Park]. AB - Soil fauna are impacted by urbanization. In order to explore the stress of different surface covers on diversity and community structure of soil fauna, we conducted this experiment in Beijing Olympic Park. In autumn of 2013, we used Baermann and Tullgren methods to study the diversity of soil fauna in the depth of 0-5 cm, 5-10 cm, 10-15 cm under four different land covers i.e. bared field (BF), totally impervious surface (TIS), partly impervious surface (PIS) and grassland (GL). The results showed that the total number of soil fauna in 100 cm3 was in order of GL (210) > PIS (193) > TIS (183) > BF (90), and the number of nematodes accounted for 72.0%-92.8% of the total number. On the vertical level, except for the TIS, the other three types of surface soil fauna had the surface gathered phenomenon. The Shannon diversity index and the Pielou evenness index of BF were lower, but the Simpson dominance index was higher than in the other land covers. The Shannon index and Margalef richness indes of GL were higher than those of the other land covers. The Shannon indexes of TIS and PIS were between the BF and GL. Except for the TIS and GL, the similarity indexes were between 0.4 0.5, indicating moderate non-similar characteristics. The diversity of soil fauna was significantly correlated with temperature, pH and available potassium. PMID- 26259456 TI - [Impacts of landscape patterns on heavy metal contamination of agricultural top soils in the Pearl River Delta, South China]. AB - Landscape patterns are known to influence many ecological processes, but the relationship between landscape patterns and soil pollution processes is not well understood. Based on 300 top soil samples, land use and cover map for the Pearl River Delta (PRD) of 2005, this study explored the characteristics and spatial pattern of heavy metal contamination of agricultural top soils and examined the impacts of landscape patterns on the heavy metal contamination in the buffers of soil samples. Research methods included geostatistical analysis, landscape pattern analysis, single-factor pollution indices, and Pearson correlation analysis. We found that: 1) out of the 235 agricultural soil samples, 3.8%, 0.4%, 17.0% and 9.4% samples exceeded the Grade II national standard for As, Pb, Cd and Ni concentrations respectively. High pollution levels were found in three cities, Guangzhou, Foshan and Zhongshan; 2) soils in the farmland were more polluted than those in the forest and orchard land, and there were no differences among different agricultural land use types in contamination level of each heavy metal (except Cd); and 3) the proportion, mean patch area as well as the degree of landscape fragmentation, landscape-level structural complexity and aggregation/connectivity of water at the buffer zone were significantly positively correlated with the contamination level of each of the four heavy metals in agricultural top soils. Part of the landscape pattern of urban land in the buffer zone also positively correlated with Pb and Cd levels (P < 0.05). On the contrary, the proportion, mean patch area and aggregation degree of forest land negatively correlated with soil Pb and Ni levels (P < 0.05); and 4) the closer to the industry land were the soil samples, the more polluted the soils were for Pb, Cd and Ni. Only landscape diversity was found to be positively correlated with soil Cd contamination. The study results provide new information and scientific basis for heavy metal pollution control and remediation, especially for agricultural soils in the PRD. PMID- 26259457 TI - [Effects of methyl jasmonate treatments and endophyte infection on growth of Achnatherum sibiricum]. AB - We used Achnatherum sibiricum, a native grass as test material and application of methyl jasmonate (MJ) to simulate herbivory, and compared the growth and physiological characters of endophyte-infected (EI) and endophyte-free (EF) plants. The results showed that MJ treatment significantly decreased the shoot growth, but significantly increased the concentrations of defensive substances such as total phenolic and lignin, and decreased the size of aphid population. Endophyte infection significantly increased the tiller number, total phenolic and lignin contents in the shoot. As for shoot biomass and total phenolic in the root, they were affected by MJ treatment. Without MJ treatment, no significant differences were found in shoot biomass or root phenolic content whether the plants were infected by endophyte or not. With MJ treatment, the shoot biomass was significantly lower and the shoot phenolic content was significantly higher in EI plants than in EF plants. Endophyte infection significantly increased resistance of the host plant to aphids, and the beneficial effect was enhanced by MJ treatments, after three applications with MJ, there were no aphids on EI plants. Overall, endophyte infection could alter the allocation pattern of the host plant between growth and defense, and MJ treatments further strengthened the defensive ability of the host plant at the cost of growth. PMID- 26259458 TI - [Evaluating the response of yield and evapotranspiration of winter wheat and the adaptation by adjusting crop variety to climate change in Huang-Huai-Hai Plain]. AB - Based on the multi-model datasets of three representative concentration pathway (RCP) emission scenarios from IPCC5, the response of yield and accumulative evapotranspiration (ET) of winter wheat to climate change in the future were assessed by VIP model. The results showed that if effects of CO2 enrichment were excluded, temperature rise would lead to a reduction in the length of the growing period for wheat under the three climate change scenarios, and the wheat yield and ET presented a decrease tendency. The positive effect of atmospheric CO2 enrichment could offset most negative effect introduced by temperature rising, indicating that atmospheric CO2 enrichment would be the prime reason of the wheat yield rising in future. In 2050s, wheat yield would increase 14.8% (decrease 2.5% without CO2 fertilization) , and ET would decrease 2.1% under RCP4.5. By adoption of new crop variety with enhanced requirement on accumulative temperature, the wheat yield would increase more significantly with CO2 fertilization, but the water consumption would also increase. Therefore, cultivar breeding new irrigation techniques and agronomical management should be explored under the challenges of climate change in the future. PMID- 26259459 TI - [Effect of waterlogging on physical traits and yield of wheat in Sichuan, China]. AB - Following a two-factor split plot design, two popular varieties ( Neimai836 and Chuanmail04) were used to study the effects of waterlogging at four growth stages (seedling, jointing, booting and anthesis) on wheat growth and yield formation during two growing seasons (2011-2012 and 2012-2013). The resulted showed that the greatest yield penalty occurred when waterlogging happened at the seedling stage (10% - 15% decrease), and it was alleviated when waterlogging happened at the other stages. Waterlogging during the seedling stage significantly reduced SPAD of 2nd-6th leaves, tillers and spike number per plant, productive ears, dry matter accumulation after flowering and dry matter at maturity. Waterlogging during the jointing stage decreased SPAD of 4th-7th leaves, and waterlogging during the booting stage reduced the SPAD of top 2nd, 3rd, 4th leaves. Waterlogging during the jointing and booting stages reduced the SPAD of flag leaf, the rate of grain filling during the gradual increase stage, the average filling rate and the 1000-grain mass. Waterlogging during the flowering stage produced limited change in yield. Therefore, waterlogging during the seedling stage was identified to have the most critical influence on wheat production under wheat/rice cropping rotations in Sichuan Province. PMID- 26259460 TI - [Physiological responses of different cucumber cultivars seedlings to iso-osmotic Mg (NO3) 2 and NaCl stress]. AB - In this study, the effects of iso-osmotic solution of Mg (NO3) 2 and NaCl on seedling growth, leaf lipid peroxidation, antioxidant enzyme activities, and osmotic adjustment substance accumulation were investigated using three cucumber cultivars with different ecotypes. Then salt tolerance was evaluated by membership function method. The results revealed that under the stress of 60 and 80 mmol x L(-1) Mg(NO3) 2 solution and its isotonic 90 and 120 mmol x L(-1) NaCl solution, the seedling traits such as height, stem diameter, leaf area, fresh and dry mass of aerial part and underground parts, and antioxidant enzymes activity were obviously decreased with the increasing concentration of Mg( NO3)2 and its isotonic NaCl in the three cucumber cultivars. Moreover, the inhibitory effects became more obvious with the increasing concentration of either Mg(NO3)2 or NaCl solution. MDA content and membrane lipid peroxidation were enhanced in cucumber seedlings. Among the three cultivars, SJ31-1 changed less than the other two cultivars regarding the reduced amplitudes of biomass, and activity of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT), and the increased amplitude of MDA. In addition, Mg (NO3)2 solution inhibited seedling growth more strongly than isotonic NaCl solution did, such difference was relatively significant with increasing the concentration of solution. The contents of proline, soluble amino acids, and soluble sugars varied depending on the cucumber genotype and salt type. The increased amplitude of proline content was the largest in SJ31-1, and that of soluble sugars was the largest in Lubai 19 when growing under salt treatment. The change of these parameters in Xintaimici was in between. Soluble sugars and soluble proteins were predominant osmolytes unde NaCl stress, whereas proline and soluble proteins were main osmolytes under Mg (NO3) 2 stress. Comprehensive evaluation showed that salt tolerance of the three cucumber cultivars was in order of SJ31-1 > Xintaimici > Lubai 19. PMID- 26259461 TI - [Effects of different potassium fertilizer application periods on the yield and quality of Fuji apple]. AB - In order to ascertain the effects of potassium fertilizer application periods on apple production, we conducted a field experiment and analyzed the differences in apple yield, fruit quality, potassium fertilizer use efficiency, and nutrient concentrations in leaves and fruits among treatments with differences in timing of potassium application. The results indicated that, compared with no potassium applied treatment (CK), all potassium fertilizer application treatments significantly increased the apple yield by 4.3%-33.2%, meanwhile, it also obviously improved the fruit quality. In comparison with the application of 100% potassium fertilizer as a base, the application of 50% or 100% of potassium fertilizer at the fruit enlargement stage (the remaining 50% applied as a base or after flowering) significantly increased the apple yield by 20.5% - 27.7% and improved the fruit quality. Compared with the application 100% potassium fertilizer at the stage of fruit enlargement, the evenly split application as base flowering stage and at the fruit enlargement: stage not only contributed to a higher yield, better quality and higher potassium use efficiency, but also maintained a relatively stable potassium concentration level in leaves. However, the split potassium fertilizer application at the flowering and fruit enlargement stages resulted in the significant decrease in concentration of calcium in fruit, which would be negative to fruit quality. In conclusion, our research suggested that evenly split application of potassium fertilizer as a base and at the fruit enlargement stage was the suitable period for apple production in Fuji apple orchards in this region. PMID- 26259462 TI - [Influences of arbuscular mycorrhizal fungus and phosphorus level on the lateral root formation of tomato seedlings]. AB - To explore the influences of arbuscular mycorrhizal fungi (AMF) and P level on plant root system architecture, tomato seedlings were inoculated with AMF strain Rhizophagus irregularis BGC JX04B under two P levels, and the influences of AMF and P level on lateral root (LR) formation of tomato seedlings were studied. Results indicated that the promoting effect of AMF on plant biomass was not evident, but significantly decreased the root to shoot ratio of plants. AMF significantly increased the primary root length but decreased the 1st order LR length and interacted with the mycorrhizal colonization period. AMF significantly lowered the 2nd-3rd order LR number and the ratio of 2nd order LR number to 1st order LR number, but did not significantly affect the 1st-2nd order LR density. High P level (50 mg x kg(-1) P) significantly promoted the plant growth and decreased the root to shoot ratio of plants. It had no significant effect on the primary root length and the 1st order root length, but significantly enhanced the 1st-3rd order LR number and the ratio of 2nd order LR number to P order LR number, increased the 1st-2nd order LR density. It suggested that AMF and P level did not share a common mechanism to influence the LR formation of tomato plants. The influence of high P level may depend on its promoting effects on nutrient uptake and plant growth, while the influence of AMF is more complex. Furthermore, the interaction between AMF and mycorrhizal colonization period implies the possible involvement of carbohydrate distribution (sugar signaling) in the regulation of root system architecture by AMF. PMID- 26259463 TI - [Effect of cadmium stress on physiological characteristics of garlic seedlings and the alleviation effects of exogenous calcium]. AB - In the experiment, the effects of exogenous cadmium (Cd2+) and calcium (Ca2+) in nutrient solution on growth, photosynthetic characteristics, enzymes activities, main mineral elements absorption of garlic seedlings were studied. The results showed that cadmium could obviously inhibit the growth of garlic seedlings, decrease the pigment contents and photosynthetic parameters (P(n), E, g(s)) of leaves, reduced the enzymes (SOD, POD, CAT) activities and increase the MDA content of leaves, and also could reduce the N, P, K, Ca, Mg contents and increase the Cd content of roots. The growth was promoted after adding exogenous calcium to garlic seedlings under cadmium stress, which reflected that the morphological indexes were increased at first and then decreased with the increase of exogenous calcium concentrations, and were maximized when the exogenous calcium was 2 or 3 mmol x L(-1). At the same time, the pigment contents and photosynthetic parameters (P(n), E, g(s)) of leaves showed a similar tendency with the morphological indexes, and they were the highest when the exogenous calcium was 2 or 3 mmol x L(-1). In addition, adding exogenous calcium to garlic seedlings under cadmium stress enhanced the enzymes (SOD, POD, CAT) activities and decreased the MDA content of leaves, also added the N, P, K, Ca, Mg contents and reduced the Cd content of roots, and the effect was best when the exogenous calcium concentration was 2 or 3 mmol x L(-1). PMID- 26259464 TI - [Soil moisture dynamics of apple orchard in Loess Plateau dryland]. AB - The soil moisture of 0-500 cm soil layer in a dryland orchard at its full fruit period was measured from 2009 to 2013 to explore the soil moisture dynamics. Results indicated that soil water consumption mainly occurred in the soil layer of 0-300 cm in normal rainfall year and below the 300 cm soil layer when the annual rainfall was less than 400 mm. The soil moisture in the 200-300 cm soil layer fluctuated most and was affected by rainfall and apple consumption. Seasonal drought usually happened between April and late June, while the accumulation of soil moisture mainly occurred in the rainy season from July to mid-October to alleviate the drought effectively in next spring. PMID- 26259465 TI - [Control of continuous potato monoculture barrier via biological soil disinfestation method in Yellow River irrigation areas of central Gansu Province, Northwest China]. AB - The potential of biological soil disinfestation (BSD) in control of continuous potato monoculture barrier was investigated in present study. BSD involves the induction of soil reduction conditions through incorporation of easily decomposed organic materials into soil, flooding the soil by irrigation, and covering the soil surface with plastic film. Control (CK) was left without cover and organic amendment as well as flooding. Field experiment was conducted for testing the effect of BSD approach on the control of continuous potato monoculture barrier, especially on tube yield, plant growth and development, suppression of soil-borne pathogen, and soil microbial community and enzyme activities. Compared with CK, BSD treatment significantly increased tuber yield by 16.1% and plant biomass by 30.8%, respectively. Meanwhile, the incidence of diseased plant and the ratio of diseased tuber in BSD treatment also significantly decreased by 68.0% and 46.7% as compared to those in CK, respectively. BSD treatment significantly increased the content of chlorophyll and branch numbers per main stem of potato plants, improved the morphological characteristics of potato root system. In the course of BSD before potato sowing, soil pH value and bacteria/fungi significantly increased, but populations of fungi and Fusarium sp. significantly decreased compared with CK. There were no significant changes in populations of bacteria and actinomycetes between CK and BSD treatments. During potato growing stage, the populations of both soil fungi and Fusarium sp. were lower in BSD treatment than those of CK. With the advance of potato growth, the population of Fusarium sp. in BSD treatment gradually increased compared with CK. There were no significant changes in soil enzyme activities in the course of BSD before potato sowing and the whole of potato growing stage. It was concluded that BSD has the potential to control continuous potato monoculture barrier and may be an important element in a sustainable and effective management strategy for potato soil-borne diseases. PMID- 26259466 TI - [Effects of different straw-returning regimes on soil organic carbon and carbon pool management index in Guanzhong Plain, Northwest China]. AB - A four-year (2008-2012) field experiment was conducted to investigate the effects of different straw-returning regimes on soil total organic carbon (TOC), labile organic carbon (LOC) and the ratio of LOC to TOC (LOC/TOC) as well as TOC stock (SCS) and soil carbon pool management index (CPMI) in a farmland with maize-wheat double cropping system in Guanzhong Plain area, Shaanxi Province, China. The results indicated that soil TOC and LOC contents and SCS were significantly increased when wheat or maize straw was returned to field, and the increasing extent showed the rising order as follows: double straw-returning > single straw returning > no straw-returning. Compared to no straw returning, a significant increase of TOC and LOC contents and SCS was found in the treatment of wheat straw chopping retention combined with maize straw chopping subsoiling retention (WC-MM), and CPMI of WC-MM was significantly higher than in the other treatments in 0-20 cm soil layer. Compared to no wheat straw returning, soil CPMIs in 0-10 cm and 10-20 cm soil layer increased by 19.1% and 67.9% for the wheat straw chopping returning treatment, and by 22.6% and 32.4% for the maize straw chopping subsoiling treatment, respectively. Correlation analysis showed that soil CPMI was a more effective index reflecting the sequestration of soil organic carbon in 0-30 cm soil layer than the ratio of LOC to TOC. This study thus suggested that WC-MM regime is the best straw-returning regime for soil organic carbon sequestration. PMID- 26259467 TI - [Effect of conservation tillage on weeds in a rotation system on the Loess Plateau of eastern Gansu, Northwest China]. AB - A field study was conducted to investigate the influences of no-tillage, stubble retention and crop type on weed density, species composition and community feature in a rotation system (winter wheat-common vetch-maize) established 12 years ago on the Loess Plateau of eastern Gansu. This study showed that the weed species composition, density and community feature varied with the change of crop phases. No-tillage practice increased the weed density at maize phase, while rotation with common vetch decreased the density in the no-tillage field. Stubble retention reduced the weed density under maize phase and the lowest density was observed in the no-tillage plus stubble retention field. No-tillage practice significantly increased the weed species diversity under winter wheat phase and decreased the diversity under common vetch phase. At maize phase, a greater species diversity index was observed in the no-tillage field. These results suggested that no-tillage practice and stubble retention possibly suppress specific weeds with the presence of some crops and crop rotation is a vital way to controlling weeds in a farming system. PMID- 26259468 TI - [Effects of bio-organic fertilizer and fungicide application on continuous cropping obstacles of cut chrysanthemum]. AB - Abstract: Fusarium wilt is a soil borne disease caused by plant continuous cropping in monoculture Chrysanthemum morifolium 'Youxiang' monoculture not only declines plant quality and yield but also decreases soil enzymes and soil microbial diversity over successive cultivation. In this article, the effects of fungicide (Carbendazim MBC), antifungal enhanced bio-organic fertilizer (BOF), and their combined application on the quality and soil enzymes activities of Chrysanthemum morifolium 'Youxiang' in continuous cropping systems were investigated. The results showed that both bioorganic fertilizer (BOF) and fungicide (MBC) single application could effectively prevent the occurrence of Fusarium wilt disease of cut chrysanthemum. Bio-organic fertilizer application was more effective on root activity, soil enzymes activities and quality (shoot height, stem diameter, leaf SPAD value, ray floret number, shoot fresh mass) improvement of cut chrysanthemum, while fungicide single application was responsible for soil enzymatic activities suppression to some extent. The combined application treatment (MBC+BOF) showed the best effects on quality improvement and soil enzyme activities promotion. PMID- 26259469 TI - [Adaptability of APSIM model in Southwestern China: A case study of winter wheat in Chongqing City]. AB - Field experimental data of winter wheat and parallel daily meteorological data at four typical stations in Chongqing City were used to calibrate and validate APSIM wheat model and determine the genetic parameters for 12 varieties of winter wheat. The results showed that there was a good agreement between the simulated and observed growth periods from sowing to emergence, flowering and maturity of wheat. Root mean squared errors (RMSEs) between simulated and observed emergence, flowering and maturity were 0-3, 1-8, and 0-8 d, respectively. Normalized root mean squared errors (NRMSEs) between simulated and observed above-ground biomass for 12 study varieties were less than 30%. NRMSE between simulated and observed yields for 10 varieties out of 12 study varieties were less than 30%. APSIM-wheat model performed well in simulating phenology, aboveground biomass and yield of winter wheat in Chongqing City, which could provide a foundational support for assessing the impact of climate change on wheat production in the study area based on the model. PMID- 26259470 TI - [Carbon, nitrogen, and phosphorus budgets of bottom-cultured clam Ruditapes philippinarum]. AB - In order to elucidate the role of bottom-cultured clams in the coastal nutrient cycle, the seasonal filtration, ingestion and biodeposition rates were in situ measured and carbon (C), nitrogen (N) and phosphorus (P) budgets of Ruditapes philippinarum among four seasons were modeled. The results showed that the scope for growth of R. philippinarum in carbon (SFG(C)), nitrogen (SFG(N)), and phosphorus (SFG(P)) all varied significantly among seasons, with the highest values in spring. Meanwhile, SFG(C) was negative in summer, SFG(N) and SFG(P) were always positive throughout the year. The seasonal variations of SFG(C), SFG(N) and SFG(P) were -3.94-49.82 mg C x ind(-1) x d(-1), 0.72-9.49 mg N x ind( 1) x d(-1), and 0.15-3.06 mg P x ind(-1) x d(-1), respectively. The net growth efficiencies in carbon (K(C2)), nitrogen (K(N2)), and phosphorus (K(P2)) also showed a distinct seasonal pattern among seasons, and ranked as K(P2) > K(N2) > K(C2). The C, N, and P budgets illustrated that the R. philippinarum population relatively used more N and P than C for growth and efficiently transferred the pelagic primary production to a higher trophic level. The current study suggested that R. philippinarum bottom-cultured at large scale might play a dominant role in the nutrient cycle of the coastal ecosystem and should be considered as an important ecological component in coastal areas. PMID- 26259471 TI - [Ecosystem service and economic valuation in the upper reaches of Xin' an River, Anhui, China for mitigating phosphorus nonpoint source pollution]. AB - A model of phosphorus purification in a watershed was established based on the export coefficient and purification index of phosphorus in different types of land cover. The model was employed to simulate the economic value of the ecosystem service with the expected water quality standard and marginal cost of pollutant purification of the upper reaches of Xin' an River of Anhui, China. The results revealed that from 2000 to 2010, some farmland outside the Tunxi, Jixi, Shexian, Yixian and Xiuning was converted to built-up land. The total amount of phosphorus exported to the upper Xin' an River decreased a little, and the main source of phosphorus pollution was farmland and built-up land. More than half of the exported phosphorus was efficiently purified by different types of land cover via flow accumulation. The pattern of purification and export of highly concentrated phosphorus showed the same trend which occurred in the northern part of the watershed including the Yangzhi River, Fengle River and Hengjiang River. Forestland and grassland did not efficiently purify phosphorus in the watershed owing to the irrational distribution of existing land cover. The total service value was 3.80 and 3.31 million Yuan in 2000 and 2010, respectively. PMID- 26259472 TI - [Research advances in iron and zinc transfer from soil to plant in intercropping systems]. AB - Intercropping facilitates the efficient utilization of land, light, water and nutrients. It is, therefore, important to increase the biodiversity of farmland and to develop sustainable ecological agriculture in both theory and practice. Intercropping helps improve the mobilization and uptake of soil iron (Fe) and zinc (Zn) and corresponding nutritional status in the plants, thus achieving grain micronutrient biofortification. In this review, phenomena of the improvement of Fe and Zn nutrition in dicotyledonous plants as affected by intercropping with gramineous plants (e.g. maize/peanut intercropping) were summarized. Moreover, the possible mechanisms in relation to interspecific rhizosphere molecular and physiological processes, as well as the changes in interspecific root morphology and distribution and microorganisms in the rhizosphere were elucidated. The accumulation, transfer and distribution of Fe and Zn in the plants in intercropping systems were also reviewed. The possible affecting factors on nutrients of Fe and Zn were analyzed. Based on the present advances in the mobilization and acquisition of soil Fe and Zn, and their accumulation and distribution in plants as well as the related management and environment influence factors, some new research questions were pointed out. Quantitative analysis, dynamic and systemic researches and field studies on Fe and Zn transfer from soil to plant in intercropping systems should be strengthened in the future. PMID- 26259473 TI - [Factors affecting activation and transference of soil colloidal phosphorus and related analysis technologies]. AB - Colloids play a key role in the transference process of phosphorus (P) in soil. Activation and transference of soil colloidal phosphorus have great effect on soil P pool and the surrounding water quality. This paper summarized the current studies on soil colloidal P, discussing the effects of the various factors (e. g., soil physical and chemical properties, fertilization, rainfall and soil amendments) on the transference of soil colloidal P. Some advanced analysis technologies (e.g., flow field-flow fractionation, transmission electron microscope-energy dispersive X-ray spectrometer, X-ray absorption near-edge structure and nuclear magnetic resonance) and methods of reducing soil colloidal P were also involved. This review would provide important information on the mechanism of soil colloidal P transference. PMID- 26259474 TI - [Tobacco cadmium health risk assessment and reduction techniques: A review]. AB - Tobacco is one of the cadmium accumulation and tolerance plants. Decreasing cadmium content of tobacco contributes to environmental safety and human health. Three aspects on tobacco cadmium research were reviewed in this paper, i.e. uptake and distribution of cadmium in tobacco, and health risk assessment of cadmium in tobacco and reduction measures. The current situations and existing challenges in the research field were discussed. The cadmium tolerance mechanisms of tobacco were reviewed, the factors on cadmium uptake were analyzed, and the general distribution of cadmium in tobacco was summarized. From the point of health risk assessment, the lack of cadmium limits in tobacco was identified, the recommended formula to calculate cadmium limits of tobacco based on atmosphere cadmium limits and digestion cadmium limits was provided and the cadmium limits of tobacco were estimated using each formula, and suggestions on cadmium limits in tobacco were presented. At last, we put forward several effective reduction measures to lower cadmium level in tobacco leaves. PMID- 26259475 TI - [Proteolysis in bacteria--a review]. AB - To adapt quickly to the environmental change, bacteria have evolved a protein quality control (PQC) network to remove unwanted proteins. AAA + ( ATPases associated with diverse cellular activities) proteases form a major part of this PQC network, and the discovery of Pup ( prokaryotic ubiquitin-like protein ) proteasome system revealed a novel mechanism of prokaryotic protein degradation. Proteolytic machines only degrade substrates bearing a degradation tag or degron to insure the proteolysis specificity. In addition, bacteria adopt different strategies to regulate the protein degradation. With the discovery of Ubiquitin mediated protein degradation in eukaryotes, it has become evident that regulated protein degradation plays a crucial role in the cell response to environment change among eukaryotes and prokaryotes. Regulation by proteolysis has been shown to be involved in diverse bacterial cellular processes including growth, division, differentiation, pathogenesis and stress response. This review will focus on the structure, degradation process, and the function of AAA + proteolytic machines in bacteria. PMID- 26259476 TI - [Structural features and functional mechanism of TonB in some Gram-negative bacteria-A review]. AB - TonB systems of gram-negative bacteria play an important role in transportation of nutriment from outside environments. TonB systems consist of plasma membrane proteins ExbB-ExbD and periplasmic protein TonB, which provide the energy to TonB dependent receptors to transport substrates. These substrates include iron, hemin, vitamin B12, carbohydrate and some transition metal elements. The energy supporting function of TonB relies on its special structure which contains N terminal domain for fixation, flexible periplasmic linker Pro-rich domain and C terminal domain for contacting receptors. The precise mechanism of TonB system is not fully understood though its structural was studied a lot. To provide insights into direction for further research of TonB, we reviewed the TonB-dependent substrates uptake, structural features, functional mechanism and expression regulation of TonB. PMID- 26259477 TI - [Research progress on baculovirus encoded inner nuclear membrane sorting motif--a review]. AB - Baculoviruses are a family of arthropod-specific viruses that mainly affect insects of the orders Lepidoptera, Hymenoptera, and Diptera. During baculovirus infection, an amplified pulse of integral membrane proteins was synthesized. The proteins use continuous membranes of the endoplasmic reticulum, outer nuclear membrane and inner nuclear membrane during their transport to the viral envelope of the occlusion-derived virus. The baculovirus encoded inner nuclear membrane sorting motif (INM-SM) functions as a sorting signal and plays pivotal roles in these processes. This review focuses on recent advances in understanding of baculovirus encoded INM-SM, including the molecular mechanisms underlining protein sorting and trafficking by INM-SM, the possible model of INM-SM involvement in integral membrane proteins trafficking and the role of INM-SM in baculovirus per os infection. These achievements and advances should help to expand the molecular understanding of protein trafficking, baculovirus molecular biology and its application in the future. PMID- 26259478 TI - [Advances in immunomodulation of microbial unmethylated CpG DNA on animal intestinal tract--a review]. AB - Unmethylated cytosine-guanine (CpG) dinucleotides motifs in bacterial DNA can be recognized by specific Toll-like receptor 9 (TLR9) in intestinal cells. As one of the intestinal immunostimulatory factors, unmethylated CpG DNA can modulate intestinal innate immune responses directly and adaptive immune responses indirectly. There is a great prospect for unmethylated CpG DNA as an immunomodulator in the rapy of intestinal diseases. This article illustrated the basic concepts of unmethylated CpG DNA, the characteristics of TLR9. We also reviewed specific applications of unmethylated CpG DNA as adjuvants in modulating intestinal immune responses. At last, we elaborated the research and application prospects of CpG DNA in the future. PMID- 26259479 TI - [Diversity of Bacillus species inhabiting on the surface and endophyte of lichens collected from Wuyi Mountain]. AB - OBJECTIVE: The present work reported the isolation, identification and diversity of Bacillus species colonizing on the surface and endophyte in lichens collected from Wuyi Mountain. METHODS: Nine lichen samples of Evernia, Stereocaulon, Menegazzia and other 6 genera belonging to 7 families were collected from Wuyi mountain nature reserve. The bacillus-like species colonizing on the surface and endophyte in these lichens were isolated and identified by 16S rRNA gene sequence analysis. RESULTS: There was no bacillus-like species isolated from Evernia, Ramalina and Lecarona. A total of 34 bacillus-like bacteria were isolated from another 6 lichen samples. These bacteria were identified as 24 species and were classified into Bacillus, Paenibacillus, Brevibacillus, Lysinibacillus and Viridiibacillus. Paenibacillus and Bacillus are the dominant genera, and accounting for 41. 2% and 35. 3% of all isolated bacteria respectively. Brevibacillus, Lysinibacillus and Viridiibacillu were first reported being isolated from lichens. There were different species and quantity of bacillus colonizing on the surface and endophyte in different lichens. The quantity of bacillus colonizing on the surface of Physcia was more than 3.85 x 10(6) cfu/g and was the largest in the isolated bacteria, while the species of bacillus colonizing on the surface and endophyte in Stereocaulon was the most abundant. Most of the isolated bacteria were colonizing on (in) one lichen genera, but Paenibacillus taichungensis, Paenibacillus odorifer, Brevibacillus agri, Lysinibacillus xylanilyticus was respectively colonizing on (in) 2-3 lichen genera and Bacillus mycoides was colonizing on (in) Menegazzia, Cladonia Physcia, and Stereocaulon. CONCLUSION: There are species and quantity diversity of bacillus colonizing on (in) lichens. PMID- 26259480 TI - [Interfering effect of an intergenic-derived sRNA of Cryptococcus neoformans]. AB - OBJECTIVE: We demonstrated the interfering effect of a new intergenic-derived sRNA of Cryptococcus neoformans. METHODS: We constructed a library of sRNAs from 20 to 25 nt, and used a reporter gene CLC1 that was fused to the testing sRNAs to show the interference effect, i. e. the degradation of the CLC1 would gene rate an albino phenotype of the transformants. RESULTS: Through the CLC-sRNA reporter system, we acquired one sRNA, sRNA-1, located to an intergenic region of the genome of C. neoformans, that displayed interfering effect on CLCl. CONCLUSIONS: In C. neoformans, the origination of sRNA may be diverse. The endogenous sRNA should play interfering function via the canonical RNAi pathway. PMID- 26259481 TI - [Effects of transporter Agp1p ubiquitination on nitrogen utilization in Saccharomyces cerevisiae]. AB - OBJECTIVE: The purpose of this work is to studythe effects of ubiquitination of key nitrogen transporter Agp1p on nitrogen utilization in Saccharomyces cerevisiae. METHODS: The ubiquitination detection vector to examine the ubiquitination process of Agp1p was constructed based on the bimolecular fluorescence complementation technology. The site-directed mutagenesis on the potential ubiquitination sites were performed to verify the effect on its ubiquitination regulation and nitrogen utilization. RESULTS: Agp1p can be ubiquitinated on the medium with glutamine, arginine, proline or ammonium. The fluorescence levels of mutant strains were down-regulated compared to the wild type strain. The quadruple mutant Agp1pK11-14-98-112R achieved the lowest level among all strains. The ubiuitination process could be significantly repressed by removing the potential ubiquitination residues. Furthermore, flask-shaking experiments with nineamino acids or urea as sole nitrogen source showed that the effect of nitrogen utilization efficiencyinthe quadruple mutant was the highest. CONCLUSION: Ubiquitination was involved in the regulation of Agp1p. Site-directed mutagenesis of potential ubiquitination sites of the transporter could significantly affect the nitrogen utilization process by altering the ubiquitination process. PMID- 26259482 TI - [Regulation of cell growth and filamentation in Candida albicans by high-affinity iron permeases Ftr1 and Ftr2]. AB - OBJECTIVE: To determine the function of high-affinity iron permeases, Ftr1 and Ftr2, we studied cell growth and filamentation ability of the ftr1/ftr1, ftr2/ftr2, and ftr1/ftr1 ftr2/ftr2 mutants under different culture conditions. METHODS: Cells of the wild type and mutants were cultured on different solid media at different temperatures. Cell growth and filamentation were observed. RESULTS: Deletion of either one of the FTR genes had no effect on the growth under all conditions tested. Deletion of both FTR1 and FTR2 led to obvious growth defect on Spider media, although addition of FeCl3 restored their growth. The double mutant also grew much more slowly on nutrients-limited synthetic media such as Lee's glucose and Lee's GlcNAc (N-acetylglucosamine). Moreover, deletion of FTR1 enhanced filamentation, whereas deletion of FTR2 weakened this ability. Deletion of both FTR1 and FTR2 recovered the ability of filamentation. CONCLUSION: Ftr1 and Ftr2 are very important for C. albicans growth under iron limited condition and may participate in the utilization of some carbon sources including GlcNAc, ethnol, and glycerol. Ftr1 plays a negative, whereas Ftr2 plays a positive role in the regulation of filamentation in C. albicans. PMID- 26259483 TI - [Effects of selective methanogenic inhibitors on methanogenesis and methanogenic communities in acetate degrading cultures]. AB - OBJECTIVE: We evaluated the role of syntrophic acetate oxidation coupled with hydrogenotrophic methanogens in three different methanogenic consortia. METHODS: Three methanogenic hexadecane degrading consortia named Y15, M82 and SK were taken from the same oily sludge of Shengli oil-field and enriched. They were incubated at 15, 35 and 55 degrees C, respectively. The consortia amended with acetate and inhibitors of NH4Cl or CH3F were further transferred and incubated at corresponding temperatures. The cultures atlate logarithmic phase were collected for terminal restriction fragment length polymorphism (T-RFLP) combined with cloning and phylogenetic analysis of 16S rRNA gene fragments. RESULTS: Gas chromatograph analysis showed that all of the consortia could grow and produce methane, but the lag phase was delayed and the growth rate was retarded in the cultures amended with inhibitor. Combination analysis of T-RFLP and clone library revealed the predominance of obligate aceticlastic Methanosaeta in the acetate cultures of Y15, M82 and SK. Under the mesophilic and thermophilic conditions, after add inginhibitor the relative abundance of aceticlastic methanogen decreased but hydrogenotrophic methanogen increased. CONCLUSION: Syntrophic acetate oxidation during methanogenic degradation of petroleum hydrocarbons occurs under mesophilic and thermophilic conditions, although the situation at low temperature seems uncertain. PMID- 26259484 TI - [High-throughput analysis of bacterial community of transition zone in littoral wetland of Wuliangsuhai eutrophic lake]. AB - OBJECTIVE: We studied soil bacterial community composition, abundance and diversity of transition zone along eutrophic lakeside wetland sediments and soils. METHODS: The total DNA was extracted according to the sediment DNA extraction. Then high-throughput pyrosequencing was used to detect soil bacterial community composition,abundance and diversity based-on 16S rRNA gene. Soil physicochemical properties were tested to analyze its effects on bacterial community according to standard methods. RESULTS: The soil bacterial community composition and relative abundance were very different across transition zone in littoral wetland. Bacteria groups mainly include Proteobacteria, Bacteroidetes, Chloroflexi, Actinobacteria, Planctomycetes and Gemmatimonadetes at phylum level. The diversity index of bacterial communities gradually increased according the land distribution, especially the phylum Proteobacteria and the genus Sulfurimonas. Correlation analysis indicated that the combination of total phosphorus, total water soluble salt and ammonium has the most significant effects on the whole bacterial community structure, and Mantel Test results indicated that the correlation was statistically significant (R = 0.8857, P = 0.037). CONCLUSION: The bacterial community structure of transition zone is quite different in littoral wetland of Wuliangsuhai eutrophic lake, where Sulfurimonas play potential important roles in biogeochemical cycles of sediments in Wuliangsuhai Lake. PMID- 26259485 TI - [Formation of huntite by Lysinibacillus sp. GW-2 strain]. AB - OBJECTIVE: We studied the formation of carbonate minerals induced by microorganism to explore the possibility of mineral capture. METHODS: Culture experiments of carbonate precipitation were done using B4 medium with 6:1 molar ration of Mg/Ca for 50 days. The same medium without inoculation was used as the control. During the cultivation, bacterial density, precipitate quantities, pH and conductivity of the medium, calciumand magnesium concentration were determined. The morphologies of precipitated carbonates were observed using scanning electron microscopy, and mineral species of carbonate were determined by X-ray diffraction. RESULTS: The main results were: (1) In the inoculation process of the Lysinibacillus sp. (GW-2 strain), we found that precipitate quantities were gradually increased with time, while precipitate was not collected in the aseptic experiments; (2) There were significant positive correlations between bacterial density and average precipitation rate (r = 0. 67, P < 0.05), precipitate quantities and pH value (r = 0.79, P < 0.05); (3) Precipitate quantities negatively correlated with conductivity, Ca2+ and Mg2+ concentration with correlation coefficients r of 0.89, 0.93, 0.98 (P < 0.001), respectively; (4) The three carbonate minerals by Lysinibacillus sp. formed according to following trend: amorphous calcium carbonate --> Huntite --> High-Mg calcite. CONCLUSIONS: The main conclusions were: (1) Lysinibacillus sp. (GW-2 strain) might induce the formation of carbonate minerals precipitation; (2) The bacterial density directly affected the precipitation of carbonate minerals, whereas pH value indirectly controlled the precipitation of carbonate minerals; (3) Decreased of conductivity, calcium and magnesium concentration of the medium could indirectly indicate the occurrence of carbonate precipitate; (4) Huntite might be formed through ageing of amorphous calcium carbonate, whereas high-Mg calcite might be formed through demagnesium of the huntite. PMID- 26259486 TI - [Actinobacterial diversity in Xinghu Wetland]. AB - OBJECTIVE: The purpose of this study was to examine the relationship between the microbial community structure of soil actinomycetes and geochemical characteristics in Xinghu wetland sediments. METHODS: The diversity and composition of the actiniobacterial community in sediments collected from 10 locations were studied using PCR-denaturing gradient gel electrophoresis. Canonical correspondence analysis was carried out to examine the relationship between environmental variables and actinobacterial community composition. RESULT: There were significant differences among the Shannon-wiener index, Richness and Evenness. Similarity analysis of actinobacteria communities in different station showed certain trends in similarity coefficients, and actinobacteria community structure similarity of the same transect was much higher than others. According to the results of sequence analysis of DGGE dominant bands belonged to the orders Nocardioidaceae, Streptomycetaceae, Micromonosporaceae, Micrococaceae, Cellulomonadaceae and Promicromonosporaceae. Canonical correspondence analysis showed that sediment water-soluble organic carbon and available phosphorus were identified as the key factor in regulating the variations of actinobacterial community composition. CONCLUSION: Xinghu Wetland is the potential place for actinobacteria diversity. This study provides fundamental data for further studies of the underline mechanisms of structure microbial groups and the isolation of actinobacteria strains of interest. PMID- 26259487 TI - [Environmental fitness of metalaxyl-resistant isolate of Phytophthora capsici]. AB - OBJECTIVE: The environmental fitness of metalaxyl-resistant isolate of Phytophthora capsici was studied for assessing the risk of metalaxyl-resistant P. capsici. METHODS: We studied the main biological characteristics, competitive ability on plate, pathogenicity on pepper plant and adaptability in soil of the laboratory-induced metalaxyl-resistant isolate of P. capsici (Pc2-3 strain), with the metalaxyl-sensitive isolate (Pc2 strain, the wild-type) as the control. RESULTS: The zoosporangia production, releasing rate of zoosporangia and germination rate of zoospores of Pc2-3 were less than that of Pc2. The temperature range, optimum temperature range and initial pH range for mycelia growth of Pc2-3 were consistent with that of Pc2, but mycelia growth rate of Pc2 3 was lower than that of Pc2. Pc2-3 exhibited significantly weak competitive ability compared with Pc2 on carrots plate. Disease incidence of pepper inoculated with Pc2-3 (14.3%) was significantly lower than that of Pc2 (88. 6% ). When pepper plant was inoculated by mixtures of zoospore suspension of Pc2-3 and Pc2 at same ratio, the disease incidence, closing to that by Pc2 strain, was 75.7% . And all the strains isolated from diseased plants in the treatment were metalaxyl-sensitive. The density of P. capsis Pc2-3 was 0.28 times of Pc2 after the soil inoculated with Pc2-3 and Pc2 respectively at same zoospores density was incubated for 20 days. Otherwise, the ratio of Pc2-3 to Pc2 was 0.42 if the metalaxyl concentration in the soil was 300 mg/kg dry soil. No matter the soil temperature and humidity were beneficial to survival of P. capsici or not, Pc2-3 showed lower soil adaptability than Pc2. CONCLUSION: The environmental fitness of metalaxyl-resistant P. capsis Pc2-3 was weaker than the metalaxyl- sensitive strain Pc2 (the wild-type). PMID- 26259488 TI - [Isolation, screening and identification of yeast for aquaculture water purification]. AB - OBJECTIVE: In order to get excellent yeast strains for aquiculture water purification, we isolated, screened and identified yeasts from the aquacultural environment and intestinal tract of shrimp. METHODS: The potential water purification ability of yeasts, isolated from the activated sludge of aquacultural environment and intestinal tract of white shrimp and mantis shrimp under normal and low temperature, was evaluated in the simulated wastewater. Morphological physio-biochemical characteristics, 5.8S rDNA ITS gene sequence analysis were used to identify the strains. RESULTS: Thirty-seven yeast strains were isolated from 3 samples, among them 16 strains were isolated under normal temperature (25 degrees C) while 21 strains were isolated under low temperature (15 degrees C). Water purification test suggested 5 strains isolated under 25 degrees C and 6 strains isolated under 15 degrees C had higher removal ability of nitrite and ammonia from water. After 48 hours treatment with DN9 and CN6, 10.64 mg/L nitrite in the water was completely removed. After 96 hours treatment, CODcr degradation rates of the 2 strains were 52% and 67%, respectively. According to morphological, physio-biochemical characteristics and 5.8S rDNA ITS gene sequence analysis, the strain DN9 was identified as Rhodotorula mucilaginosa and CN6 as Rhodosporidium paludigenum. CONCLUSION: Strains DN9 and CN6 would be promising for water purification in aquiculture. PMID- 26259489 TI - [Correlation between Type IV secretion system component VirD4 and virulence for Streptococcus suis 2]. AB - OBJECTIVE: In order to study the role of SS2 Type IV Secretion System VirD4 in evasion of the host innate immune killing, we constructed a knockout mutant AVirD4. Then we studied its biological activity and virulence. METHODS: The two VirD4 flanking DNA sequences were amplified using genome of 05ZYH33 as template. We also amplified the Cm sequence of shuttle vector pSET1, and through overlap extension PCR we connected the three fragments together. Using suicide vector pSET4s, we constructed the recombinant gene knockout vector pSET4s::VirD4. The mutant AVirD4 was successfully constructed by allelic replacement. Virulence of mutant strain was compared with wild type strain 05ZYH33 through in vitro bactericidal assays, competitive infection and challenge experiment of CD1 mice. RESULTS: Mutant strain AVirD4 was constructed successfully, its virulence attenuated compared to the wild type strain. CONCLUSION: These findings indicated that Type IV Secretion System component VirD4 contributed to the virulence of S. suis with important functions in evading innate immunocyte killing. PMID- 26259490 TI - [TLR-4 involvement in pyroptosis of mice with pulmonary inflammation infected by Actinobacillus pleuropneumoniae]. AB - OBJECTIVE: Pyroptosis is a caspase-1 dependent programmed cell death and involves pathogenesis of infectious diseases by releasing many pro-inflammatory cytokines to induced inflammation. TLR-4 plays an important role in mediating pathogenesis of some infectious diseases. In this study, we detected the expression of TLR-4 and some molecules (e. g caspase-1, TNF-alpha, IL-1beta, IL-6, IL-18 ) related with pyroptosis to determine its involvement and mechanisms of pulmonary inflammation in mice infected by A. pleuropneumoniae. METHODS: Mice were intranasally infected by A. pleuropneumoniae and killed 48 hours post infection. Pulmonary gross lesion and histological pathology by H-E were observed. Expression levels of caspase-1 , caspase-3, TNF-alpha, IL-1beta, IL-6, IL-18, and TLR-4 in lung of mice were detected by RT-PCR and qPCR. RESULTS: Serious pulmonary hemorrhage and inflammation in infected mice were observed. Expression levels of caspase-1, caspase-3, TNF-alpha, IL-1beta, IL-6, IL-18 and TLR-4 increased, and expression levels of caspase-3 were not changed in lung of infected mice. CONCLUSION: TLR-4 might be involved in pulmonary inflammation of mice infected by A. pleuropneumoniae. After induced by activated TLR-4 some cells in this lesion expressed pro-inflammatory cytokines. These cytokines would induce pulmonary inflammation. This lesion might involve pyroptosis with caspase-1 expression. PMID- 26259492 TI - Comparison of cap lamp and laser illumination for detecting visual escape cues in smoke. AB - The Illuminating Engineering Society of North America reports that an underground mine is the most difficult environment to illuminate (Rea, 2000). Researchers at the U.S. National Institute for Occupational Safety and Health (NIOSH) Office of Mine Safety and Health Research (OMSHR) are conducting ongoing studies designed to explore different lighting technologies for improving mine safety. Underground miners use different visual cues to escape from a smoke-filled environment. Primary and secondary escapeways are marked with reflective ceiling tags of various colors. Miners also look for mine rail tracks. The main objective of this paper is to compare different lighting types and ceiling tag colors to differentiate what works best in a smoke-filled environment. Various cap lamps (LED and incandescent) and lasers (red, blue, green) were compared to see which options resulted in the longest detection distances for red, green and blue reflective markers and a section of mine rail track. All targets advanced toward the human subject inside of a smoke-filled room to simulate the subject walking in a mine environment. Detection distances were recorded and analyzed to find the best cap lamp, laser color and target color in a smoke environment. Results show that cap lamp, laser color and target color do make a difference in detection distances and are perceived differently based on subject age. Cap lamps were superior to lasers in all circumstances of ceiling tag detection, with the exception of the green laser. The incandescent cap lamp worked best in the simulated smoke compared to the LED cap lamps. The green laser was the best color for detecting the tags and track compared to the red and blue lasers. The green tags were the easiest color to detect on the ceiling. On average, the track was easier for the subjects to detect than the ceiling tags. PMID- 26259493 TI - The role of censoring on progression free survival: oncologist discretion advised. AB - Censoring is increasingly appreciated as a potential bias affecting estimates of progression free survival (PFS) in randomised trials. In this commentary, we explore the central assumption of censoring. Censored patients are considered no more or less likely to undergo the event of interest than those who remain in the analysis. Instead however, if one makes alternate assumptions, that censored patients are different than those who remain on the trial, estimates of PFS change. Using the example of the recent BOLERO-2 trial of exemestane and everolimus, we show that by altering the assumptions for censoring, the major conclusions of clinical trials may change. As such, the number of censored patients at each time interval should be routinely reported in randomised trials to better understand the implications of censoring. PMID- 26259494 TI - Thymoma and thymic carcinoma in children and adolescents: a report from the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT). AB - BACKGROUND: Thymomas and thymic carcinomas belong to a group of thymic epithelial tumours arising from the anterior mediastinum and, are extremely rare in children in which no therapeutic guidelines have been established. The aim is to describe paediatric characteristics of these tumours and give some therapeutic indications. METHODS: Retrospective analysis of clinical data and therapeutic characteristics of paediatric patients less than 18years with thymic tumours treated between 2000 and 2012 registered in the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) database of the cooperating national rare paediatric tumour working groups from France, Italy, Germany and Poland. RESULTS: Sixteen children with thymoma, median age 11years and 20 patients with thymic carcinoma, median age 14years were enrolled into study. At diagnosis complete primary resection was possible in 11 patients with thymoma and one with thymic carcinoma; resection with microscopic residue was performed in three cases and incomplete resection with macroscopic residue in four patients. Chemotherapy with various regimens was administered to 22 children; 17 of them as neoadjuvant chemotherapy. Eight patients with thymic carcinoma received additional radiotherapy. Seventeen children died (15 thymic carcinoma, two thymoma). Five year overall survival for patients with thymic carcinoma is 21.0+/-10.0%. CONCLUSIONS: This study confirms the possibility to perform European retrospective analysis even in very rare paediatric tumours. Thymic carcinoma is associated with paediatric patients to give a very poor prognosis independently despite multimodal management. Multidisciplinary, multicenter approach and collaboration with adults' physician are necessary in order to propose homogenous guidelines. PMID- 26259495 TI - Investigation of Oxytocin Secretion in Anorexia Nervosa and Bulimia Nervosa: Relationships to Temperament Personality Dimensions. AB - Published studies suggested an implication of oxytocin in some temperament characteristics of personality. Therefore, we measured oxytocin secretion in 23 women with anorexia nervosa (AN), 27 with bulimia nervosa (BN) and 19 healthy controls and explored the relationships between circulating oxytocin and patients' personality traits. Plasma oxytocin levels were significantly reduced in AN women but not in BN ones. In healthy women, the attachment subscale scores of the reward dependence temperament and the harm avoidance (HA) scores explained 82% of the variability in circulating oxytocin. In BN patients, plasma oxytocin resulted to be negatively correlated with HA, whereas no significant correlations emerged in AN patients. These findings confirm a dysregulation of oxytocin production in AN but not in BN and show, for the first time, a disruption of the associations between hormone levels and patients' temperament traits, which may have a role in certain deranged behaviours of eating disorder patients. PMID- 26259496 TI - Early second-trimester plasma protein profiling using multiplexed isobaric tandem mass tag (TMT) labeling predicts gestational diabetes mellitus. AB - AIMS: Gestational diabetes mellitus (GDM) is associated with an increased risk of serious complications for mother and child during pregnancy. The main option for diagnosis of GDM is 75 g oral glucose tolerance test (OGTT) at 24-28 gestation weeks, when harms to both mother and child have already potentially occurred. The aim of this study was to investigate new biomarkers for earlier detection and assessment of GDM at early second trimester (16-18 gestation weeks). METHODS: We systematically used multiplexed isobaric tandem mass tag labeling combined with liquid chromatography mass spectrometry (LC-MS/MS) to screen differentially expressed proteins in plasma collected at 16-18 gestational weeks between pregnant women with and without GDM outcome. RESULTS: A total of 828 proteins were identified, of which 36 proteins implicated in immune response, inflammation, transport, platelet aggregation, catalyze and defense response were identified as differentially regulated proteins in GDM. To assess the validity of the results, four selected proteins including C-reactive protein, sex hormone binding globulin, Ficolin 3 and pregnancy-specific beta-1-glycoprotein 4 were selected for subsequent Western blot analysis. CONCLUSIONS: This is the first comprehensive study that integrates multiple state-of-the-art proteomic technologies to discover the earlier potential plasma biomarkers for GDM. PMID- 26259497 TI - The author's reply: Pancreatic fat and hepato-metabolic features in obese children with nonalcoholic fatty liver disease. PMID- 26259498 TI - Levels and limits in artificial selection of communities. AB - Artificial selection of individuals has been determinant in the elaboration of the Darwinian theory of natural selection. Nowadays, artificial selection of ecosystems has proven its efficiency and could contribute to a theory of natural selection at several organisation levels. Here, we were not interested in identifying mechanisms of adaptation to selection, but in establishing the proof of principle that a specific structure of interaction network emerges under ecosystem artificial selection. We also investigated the limits in ecosystem artificial selection to evaluate its potential in terms of managing ecosystem function. By artificially selecting microbial communities for low CO2 emissions over 21 generations (n = 7560), we found a very high heritability of community phenotype (52%). Artificial selection was responsible for simpler interaction networks with lower interaction richness. Phenotype variance and heritability both decreased across generations, suggesting that selection was more likely limited by sampling effects than by stochastic ecosystem dynamics. PMID- 26259499 TI - National decline in invasive prenatal diagnostic procedures in association with uptake of combined first trimester and cell-free DNA aneuploidy screening. AB - In late 2012, a new screening test for fetal aneuploidy based on circulating cell free DNA (cfDNA) became available to Australian women. The introduction of this technology in the United States has led to a reduction in invasive diagnostic procedures. Analysis of the number of amniocentesis and chorionic villus sampling (CVS) procedures performed in Australia from 1994 to 2014 shows that the introduction of cfDNA testing has been associated with the most rapid decline in invasive procedures in the last 20 years. This change has important implications for training in, and maintenance of, the procedural skills of amniocentesis and CVS. PMID- 26259500 TI - Biomechanical evaluation of a new treatment method for distal tibia fractures. PMID- 26259501 TI - Birth outcomes of patients with isolated anorectal malformations: A population based case-control study. AB - In most patients affected by isolated anorectal malformation (IARM) the etiology is largely unknown. Thus, the aim of our project was to analyze possible risk factors for IARM. In the first step, birth outcomes of cases with IARM were analyzed on the basis of maternal socio-demographic variables, and these data are presented in this paper. Gestational age at delivery, birthweight, preterm birth, low birthweight and small for gestational age of cases with IARM were evaluated in the function of maternal age, birth/pregnancy order, marital and employment status of mothers in the population-based large dataset of the Hungarian Case Control Surveillance of Congenital Abnormalities, 1980-1996. The study samples included 231 live-born cases with IARM, 361 matched and 38 151 population controls without any defect. IARMs are more frequent in males, twins and newborn infants with low birthweight and small-for-gestational-age, the latter being the consequence of intrauterine growth restriction. In addition, mothers of cases were younger but with higher birth order, and had lower socio-economic status. These maternal variables are characteristic for the gypsy population in Hungary. The higher proportion of gypsy women among the mothers of cases with IARM was confirmed during the home visits of the study. Male sex and intrauterine growth restriction of cases, in addition to low socioeconomic status and gypsy origin of mothers may have a role in the risk of IARMs. PMID- 26259502 TI - Nonmyeloablative allogeneic stem cell transplantation for chronic lymphocytic leukaemia offers the possibility of disease control with minimal morbidity and mortality--a single institution experience. AB - Allogeneic stem cell transplantation is a treatment option for patients with poor risk CLL. We conducted a retrospective analysis of all CLL patients allografted at our institution, the University Hospital of Cologne, Germany. Data was collected on 40 patients from 2004 to 2012. The mean age was 54, and the majority were male (75 %). On average, the patients were diagnosed 6 years (range 2-12) prior to transplant with an average of 4 years (range 1-8) from time of first line therapy to transplant. The remission states at the time of transplant were complete remission (CR) (n = 4), stable disease (n = 10), partial remission (n = 20) and progressive disease (n = 6). Only reduced intensity conditioning regimens were employed. The average CD34(+) cell dose was 4.16 * 10(6)/kg. Neutrophil engraftment was seen by day +17 (range 10-23) post-transplant, and 88 % achieved 95-100 % donor chimerism by day 100. Overall survival, progression-free survival and non-relapse mortality at 2 years post-transplant were 65, 52.5 and 27.5 %, respectively. A total of 51 % of patients were found to be minimal residual disease (MRD)-negative at 1 year post-transplant. Our single-centre experience confirms the valuable role of allogeneic stem cell transplantation (allo-SCT) in the treatment of poor risk CLL patients with promising long-term survival and acceptable transplant-related mortality. The advent of newer therapeutic agents should not hinder the consideration of allo-SCT for this patient cohort as it remains the only curative option for these patients. PMID- 26259504 TI - Detection of red blood cell antibodies in mitogen-stimulated cultures from patients with hereditary spherocytosis. AB - BACKGROUND: Hereditary spherocytosis (HS) is a congenital hemolytic anemia caused by defects in red blood cell (RBC) membrane proteins leading to premature RBC clearance in the spleen. The presence of RBC autoantibodies has never been extensively investigated in HS. STUDY DESIGN AND METHODS: RBC antibody-bound immunoglobulin (Ig)G was investigated in 91 consecutive HS patients by mitogen stimulated direct antiglobulin test (MS-DAT), a sensitive method able to magnify latent RBC antibody autoimmunity and related with hemolytic variables, previous splenectomy, and type of membrane defect. RESULTS: A total of 61% of HS cases had RBC antibodies by MS-DAT (29 Band 3, 17 spectrin deficiency, and nine no defined defect). The amount of RBC-bound IgG was greater in HS compared with controls (236 +/- 192 ng/mL vs. 52 +/- 29 ng/mL, p < 0.0001), although lower than that observed in autoimmune hemolytic anemia (AIHA; 634 +/- 371 ng/mL vs. 236 +/- 192 ng/mL, p < 0.0001). Western blot experiments showed that purified IgG fraction from MS-DAT-positive patients bind to alpha- and beta-spectrin, Band 3, and Band 4.9. Positive cases displayed increased reticulocytosis and slightly reduced hemoglobin (Hb) values compared to negative ones. Patients displaying RBC-bound IgG of more than 250 ng/mL (the positive threshold of AIHA) showed increased number of spherocytes and mainly had spectrin deficiency. RBC-bound IgG and free Hb increased over time after storage at 4 degrees C, a surrogate of ex vivo aging, more evidently in HS than controls, and particularly in Band 3 deficiency. CONCLUSION: RBC autoantibodies were detected by MS-DAT in more than a half of HS patients. Positive cases showed a more evident hemolytic pattern suggesting a pathogenic role of these autoantibodies in RBC opsonization and splenic removal. PMID- 26259505 TI - The Role of Eating Habits on the Iron Status of Pregnant Women. AB - OBJECTIVE: This study highlights the relationship between some eating habits and iron status during pregnancy. SUBJECTS: The study included 219 healthy pregnant women aged 27.6 +/- 5.7 years from southern Bulgaria. METHODS: Subjects' iron status was assessed on the basis of the following iron indicators: hemoglobin (Hb), serum ferritin (SF), serum transferrin receptor (sTfR), and body iron index (mg/kg). RESULTS: Severe anemia among the women from southern Bulgaria was not observed. Advanced pregnancy and some eating habits are factors that deteriorate iron status. Women who had consumed fish at least 3 times a week had lower levels of sTfR (r = 0.008), higher levels of SF (r = 0.05), and lower levels of body iron (r = 0.018). Frequent legume consumption was related to increased levels of sTfR (r = 0.036). Pregnant women with a high frequency of coffee consumption had lower values of body iron (r < 0.0001). Women who had consumed cow's milk at least 3 times a week had lower levels of SF (r = 0.026) and body iron (r = 0.042). CONCLUSIONS: Regular consumption of fish and legumes, rarely drinking coffee, and milk consumption during the intervals between food intake are conditions for optimization of iron status during pregnancy. PMID- 26259506 TI - Dietary intake of calcium and magnesium and the metabolic syndrome in the National Health and Nutrition Examination (NHANES) 2001-2010 data. AB - Higher dietary intakes of Mg and Ca, individually, have been associated with a decreased risk for the metabolic syndrome (MetSyn). Experimental studies suggest that a higher intra-cellular ratio of Ca:Mg, which may be induced by a diet high in Ca and low in Mg, may lead to hypertension and insulin resistance. However, no previous epidemiological studies have examined the effects of the combined intake of Mg and Ca on MetSyn. Thus, we evaluated the association between dietary intakes of Ca and Mg (using 24-h recalls), independently and in combination, and MetSyn in the National Health and Nutrition Examination Study 2001-2010 data, which included 9148 adults (4549 men and 4599 women), with complete information on relevant nutrient, demographic, anthropometric and biomarker variables. We found an inverse association between the highest (>355 mg/d) v. the lowest (<197 mg/d) quartile of Mg and MetSyn (OR 0.70; 95% CI 0.57, 0.86). Women who met the RDA for both Mg (310-320 mg/d) and Ca (1000-1200 mg/d) had the greatest reduced odds of MetSyn (OR 0.59; 95% CI 0.45, 0.76). In men, meeting the RDA for Mg (400 420 mg/d) and Ca (1000-1200 mg/d), individually or in combination, was not associated with MetSyn; however, men with intakes in the highest quartile for Mg (>= 386 mg/d) and Ca (>= 1224 mg/d) had a lower odds of MetSyn (OR 0.74; 95% CI 0.59, 0.93). Our results suggest that women who meet the RDA for Mg and Ca have a reduced odds of MetSyn but men may require Ca levels higher than the RDA to be protected against MetSyn. PMID- 26259507 TI - Reconstituted AIM2 inflammasome in cell-free system. AB - Absent in melanoma 2 (AIM2) is an intracellular pattern-recognition receptor, which is a member of the PYHIN protein family, consisting of a PYD domain and an IFN-inducible nuclear localization (HIN) domain. AIM2 is reported to oligomerize with adaptor protein ASC upon sensing bacterial and viral cytosolic DNA in order to form the AIM2 inflammasome, which activates caspase-1 leading to IL-1beta secretion. Dysregulation of AIM2 inflammasome is supposed to result in autoinflammatory and autoimmune diseases. Thus, the development of new targeted drugs against AIM2 inflammasome would be important for the treatment of these diseases. However, since AIM2 inflammasome is an intracellular receptor, enforced internalization of both ligands and candidate molecules is necessary for the screening of AIM2-inflammasome-targeted molecules. We developed a reconstituted AIM2 inflammasome in a cell-free system with amplified luminescent proximity homogeneous assay (Alpha). Strong Alpha signal was detected upon incubation with poly-deoxyadenylic-deoxythymidylic acid, poly(dA:dT), whereas no Alpha signal was detected upon incubation with muramyl dipeptide, one of the NLR ligands of Nod2 ligand. The interaction between AIM2 and ASC was disrupted by an anti-human ASC monoclonal antibody, CRID3, a class of diarylsulfonylurea-containing compounds, and glycyrrhizin, a substance found in liquorice root. Thus, the reconstituted AIM2 inflammasome in a cell-free system is useful for screening AIM2-inflammasome targeted therapeutic molecules. PMID- 26259508 TI - Temporal and spatial influences incur reconfiguration of Arctic heathland soil bacterial community structure. AB - Microbial responses to Arctic climate change could radically alter the stability of major stores of soil carbon. However, the sensitivity of plot-scale experiments simulating climate change effects on Arctic heathland soils to potential confounding effects of spatial and temporal changes in soil microbial communities is unknown. Here, the variation in heathland soil bacterial communities at two survey sites in Sweden between spring and summer 2013 and at scales between 0-1 m and, 1-100 m and between sites (> 100 m) were investigated in parallel using 16S rRNA gene T-RFLP and amplicon sequencing. T-RFLP did not reveal spatial structuring of communities at scales < 100 m in any site or season. However, temporal changes were striking. Amplicon sequencing corroborated shifts from r- to K-selected taxon-dominated communities, influencing in silico predictions of functional potential. Network analyses reveal temporal keystone taxa, with a spring betaproteobacterial sub-network centred upon a Burkholderia operational taxonomic unit (OTU) and a reconfiguration to a summer sub-network centred upon an alphaproteobacterial OTU. Although spatial structuring effects may not confound comparison between plot-scale treatments, temporal change is a significant influence. Moreover, the prominence of two temporally exclusive keystone taxa suggests that the stability of Arctic heathland soil bacterial communities could be disproportionally influenced by seasonal perturbations affecting individual taxa. PMID- 26259509 TI - Water impacting on superhydrophobic macrotextures. AB - It has been recently shown that the presence of macrotextures on superhydrophobic materials can markedly modify the dynamics of water impacting them, and in particular significantly reduce the contact time of bouncing drops, compared with what is observed on a flat surface. This finding constitutes a significant step in the maximization of water repellency, since it enables to minimize even further the contact between solid and liquid. It also opens a new axis of research on the design of super-structures to induce specific functions such as anti-freezing, liquid fragmentation and/or recomposition, guiding, trapping and so on. Here we show that the contact time of drops bouncing on a repellent macrotexture takes discrete values when varying the impact speed. This allows us to propose a quantitative analysis of the reduction of contact time and thus to understand how and why macrotextures can control the dynamical properties of bouncing drops. PMID- 26259510 TI - The Association of Fibrinous Pleural Effusion with Survival and Complications in Horses with Pleuropneumonia (2002-2012): 74 Cases. AB - BACKGROUND: Fibrinous parapneumonic pleural effusions are associated with decreased efficacy of pleural fluid drainage and increased risk of medical treatment failure in people, but similar associations have not been established in horses. HYPOTHESIS/OBJECTIVES: We hypothesized that fibrin deposition in the pleural cavity of horses with parapneumonic effusions increases the risk of poor outcome. ANIMALS: Seventy four horses with bacterial pleuropneumonia diagnosed by culture and cytology of tracheal aspirates, pleural fluid, or both, and pleural effusion diagnosed by ultrasonographic examination. METHODS: Retrospective study of cases was from 2002 to 2012. Information obtained from the medical records included signalment, history, sonographic findings, treatments, and outcome. The primary outcome investigated was survival and secondary outcomes were development of complications and surgical intervention. Fisher's exact test and logistic regression were applied for categorical variables. A t-test was used to find differences in continuous variables between groups. RESULTS: Seventy four horses met study criteria and 50 (68%) survived. Fibrinous pleural effusion was associated with higher respiratory rate and pleural fluid height at admission, necrotizing pneumonia, increased number of indwelling thoracic drains required for treatment, and decreased survival. CONCLUSIONS AND CLINICAL IMPORTANCE: Fibrin accumulation in parapneumonic effusions is associated with increased mortality. Direct fibrinolytic treatment might be indicated in affected horses. PMID- 26259511 TI - Three-dimensional refractive index tomograms and deformability of individual human red blood cells from cord blood of newborn infants and maternal blood. AB - Red blood cells (RBCs) from the cord blood of newborn infants have distinctive functions in fetal and infant development. To systematically investigate the biophysical characteristics of individual cord RBCs in newborn infants, a comparative study was performed on RBCs from the cord blood of newborn infants and from adult mothers or nonpregnant women using optical holographic microtomography. Optical measurements of the distributions of the three dimensional refractive indices and the dynamic membrane fluctuations of individual RBCs were used to investigate the morphological, biochemical, and mechanical properties of cord, maternal, and adult RBCs at the individual cell level. The volume and surface area of the cord RBCs were significantly larger than those of the RBCs from nonpregnant women, and the cord RBCs had more flattened shapes than that of the RBCs in adults. In addition, the hemoglobin (Hb) content in the cord RBCs from newborns was significantly higher. The Hb concentration in the cord RBCs was higher than that in the nonpregnant women or maternal RBCs, but they were within the physiological range of adults. Interestingly, the amplitudes of the dynamic membrane fluctuations in cord RBCs were comparable to those in nonpregnant women and maternal RBCs, suggesting that the deformability of cord RBCs is similar to that of healthy RBCs in adults. PMID- 26259512 TI - Matrine derivative WM130 inhibits hepatocellular carcinoma by suppressing EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways. AB - Matrine, a sophora alkaloid, has been demonstrated to exert antitumor effects on many types of cancer. However, its bioactivity is weak and its potential druggability is low. We modified the structure of matrine and obtained a new matrine derivative, WM130 (C30N4H40SO5F), which exhibited better pharmacological activities than matrine. In this study, we investigated the antitumor activity and the underlying mechanisms of WM130 on hepatocellular carcinoma (HCC) cells in vitro and in vivo, and found that WM130 inhibited the proliferation, invasion, migration and induced apoptosis of HCC cells in a dose-dependent manner. Furthermore, after treatment with WM130, the expressions of p-EGFR, p-ERK, p-AKT, MMP-2 and the ratio of Bcl-2/Bax were significantly down-regulated, whereas the expression of PTEN was increased in HCC cells. Moreover, WM130 inhibited Huh-7 xenograft tumor growth in a dose-dependent manner after intravenous administration. Immunohistochemistry results demonstrated that WM130 treatment resulted in down-regulation of p-EGFR, MMP-2, and Ki67 and up-regulation of PTEN. The findings indicated that WM130 could inhibit cell proliferation, invasion, migration and induced apoptosis in HCC cells by suppressing EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways and may be a novel effective candidate for HCC treatment. PMID- 26259513 TI - IFITM1 promotes the metastasis of human colorectal cancer via CAV-1. AB - Interferon-induced transmembrane protein 1 (IFITM1) is one of the interferon induced transmembrane protein family members. In this study, we reported that the elevated IFITM1 expression in human colorectal cancer (CRC) significantly correlated with CRC lymph node and distance metastasis as well as a more advanced clinical stage. Importantly, elevated IFITM1 expression is an independent prognostic factor for poor survival. To investigate the molecular mechanisms, we showed that over-expression of IFITM1 in CRC cells promoted, whereas knockdown of IFITM1 expression inhibited, cell migration/invasion and tumorigenicity in vitro. Furthermore, we identified Caveolin-1 (CAV1) as a downstream target of IFITM1 induced cell invasion, as knockdown of CAV1 abrogated siIFITM1 mediated inhibition of cell invasion in CRC cells. In addition, in a CRC cohort of 229 patients, the expression of IFITM1 inversely correlated with the expression of CAV1. These results suggested that IFITM1 promotes the aggressiveness of CRC cells, and it is a potential prognostic marker and therapeutic target for CRC. PMID- 26259515 TI - Multifunctional luminescent nanomaterials from NaLa(MoO4)2:Eu(3+)/Tb(3+) with tunable decay lifetimes, emission colors, and enhanced cell viability. AB - A facile, but effective, method has been developed for large-scale preparation of NaLa(MoO4)2 nanorods and microflowers co-doped with Eu(3+) and Tb(3+) ions (abbreviated as: NLM:Ln(3+)). The as-synthesized nanomaterials possess a pure tetragonal phase with variable morphologies from shuttle-like nanorods to microflowers by controlling the reaction temperature and the amount of ethylene glycol used. Consequently, the resulting nanomaterials exhibit superb luminescent emissions over the visible region from red through yellow to green by simply changing the relative doping ratios of Eu(3+) to Tb(3+) ions. Biocompatibility study indicates that the addition of NLM:Ln(3+) nanomaterials can stimulate the growth of normal human retinal pigment epithelium (ARPE-19) cells. Therefore, the newly-developed NaLa(MoO4)2 nanomaterials hold potentials for a wide range of multifunctional applications, including bioimaging, security protection, optical display, optoelectronics for information storage, and cell stimulation. PMID- 26259517 TI - Effectiveness of a brief theory-based health promotion intervention among adults at high risk of type 2 diabetes: One-year results from a randomised trial in a community setting. AB - AIM: To examine the effect of a brief theory-based health promotion intervention delivered in the community on health behaviour and diabetes-related risk factors among Danish adults at high risk of diabetes. METHODS: A randomised trial was conducted among 127 individuals aged 28 to 70 with fasting plasma glucose: 6.1 6.9 mmol/l and/or HbA1c: 6.0-<6.5% (42-<48 mmol/mol) recruited from general practice in Holstebro, Denmark. Participants were randomised to a control group or to receive the intervention delivered over four 2h group sessions during five weeks, and two further sessions after one and six months. Questionnaire data and clinical measures were collected at baseline, three months and one year after intervention. Primary outcomes; total-fat intake <30% of energy intake; saturated fat intake <10% of energy intake; fibre-intake >=15 g/1000 kcal; weight reduction >5%; changes in physical activity. RESULTS: 85% attended one-year follow-up. After adjusting for gender, age and education, Odds ratio (OR) (95% CI) intervention vs control: total-fat intake <30% energy intake: 0.52 (0.22;1.20), saturated-fat intake <10% energy intake: 1.22 (0.52;2.87), fibre intake >= 15 g/1000 kcal: 1.18 (0.48;2.92), weight reduction >5%: 2.47 (0.95; 6.39). beta (95% CI) between intervention vs control in changes from baseline: IPAQ, MET min/week: -236 (-2760; 2288), waist circumference,cm: -2.5 (-4.5; -0.5); systolic blood pressure, mmHg: -4.6 (-8.8; -0.3). CONCLUSION: A brief theory-based health promotion intervention delivered in the community indicated effect on weight, waist circumference and systolic blood pressure at one year among Danish adults at high risk of diabetes. No effect was shown on diets or physical activity. PMID- 26259516 TI - Neural crest specification by Prohibitin1 depends on transcriptional regulation of prl3 and vangl1. AB - A complex network of transcription factors regulates specification of neural crest cells at early neurula stage by stabilizing neural crest identity and activating neural crest effector genes so that distinct subpopulations evolve. In this network, c-myc acts on top of the gene hierarchy controlling snail2, AP2 and prohibitin1 (phb1) expression. While snail2 and AP2 are well studied neural crest specifier genes little is known about the role of phb1 in this process. To identify phb1 regulated genes we analyzed the transcriptome of neural crest explants of phb1 morphant Xenopus embryos. Among 147 phb1 regulated genes we identified the membrane-associated protein-tyrosine phosphatase PRP4A3 (prl3) and the atypical cadherin and Wnt-PCP component van gogh like1 (vangl1). Gain of function, loss of function and epistasis experiments allowed us to allocate both genes in the neural crest specification network between phb1 and twist. Interestingly, both, vangl1 and prl3 regulate only a small subset of neural crest marker genes. The identification of two membrane-associated proteins as novel neural crest specifiers indicates that in addition to gene regulation by combinatory effects of transcription factors also post-translational modifications (prl3) and cell-cell adhesion and/or regulation of cell-polarity (vangl1) specify the identity of neural crest cell populations. genesis 53:627 639, 2015. (c) 2015 Wiley Periodicals, Inc. PMID- 26259514 TI - Initiation of mRNA translation in bacteria: structural and dynamic aspects. AB - Initiation of mRNA translation is a major checkpoint for regulating level and fidelity of protein synthesis. Being rate limiting in protein synthesis, translation initiation also represents the target of many post-transcriptional mechanisms regulating gene expression. The process begins with the formation of an unstable 30S pre-initiation complex (30S pre-IC) containing initiation factors (IFs) IF1, IF2 and IF3, the translation initiation region of an mRNA and initiator fMet-tRNA whose codon and anticodon pair in the P-site following a first-order rearrangement of the 30S pre-IC produces a locked 30S initiation complex (30SIC); this is docked by the 50S subunit to form a 70S complex that, following several conformational changes, positional readjustments of its ligands and ejection of the IFs, becomes a 70S initiation complex productive in initiation dipeptide formation. The first EF-G-dependent translocation marks the beginning of the elongation phase of translation. Here, we review structural, mechanistic and dynamical aspects of this process. PMID- 26259518 TI - Impairment of autophagosome-lysosome fusion in the buff mutant mice with the VPS33A(D251E) mutation. AB - The HOPS (homotypic fusion and protein sorting) complex functions in endocytic and autophagic pathways in both lower eukaryotes and mammalian cells through its involvement in fusion events between endosomes and lysosomes or autophagosomes and lysosomes. However, the differential molecular mechanisms underlying these fusion processes are largely unknown. Buff (bf) is a mouse mutant that carries an Asp251-to-Glu point mutation (D251E) in the VPS33A protein, a tethering protein and a core subunit of the HOPS complex. Bf mice showed impaired spontaneous locomotor activity, motor learning, and autophagic activity. Although the gross anatomy of the brain was apparently normal, the number of Purkinje cells was significantly reduced. Furthermore, we found that fusion between autophagosomes and lysosomes was defective in bf cells without compromising the endocytic pathway. The direct association of mutant VPS33A(D251E) with the autophagic SNARE complex, STX17 (syntaxin 17)-VAMP8-SNAP29, was enhanced. In addition, the VPS33A(D251E) mutation enhanced interactions with other HOPS subunits, namely VPS41, VPS39, VPS18, and VPS11, except for VPS16. Reduction of the interactions between VPS33A(Y440D) and several other HOPS subunits led to decreased association with STX17. These results suggest that the VPS33A(D251E) mutation plays dual roles by increasing the HOPS complex assembly and its association with the autophagic SNARE complex, which selectively affects the autophagosome lysosome fusion that impairs basal autophagic activity and induces Purkinje cell loss. PMID- 26259519 TI - A Quantitative Framework to Evaluate Proarrhythmic Risk in a First-in-Human Study to Support Waiver of a Thorough QT Study. AB - The effects of GS-4997 (apoptosis signal-regulating kinase 1 inhibitor) on cardiac repolarization were evaluated using a systematic modeling approach in a first-in-human (FIH) study. High quality, intensive, time-matched 12-lead electrocardiograms (ECGs) were obtained in this placebo-controlled, single and multiple-ascending dose study in healthy subjects. Model development entailed linearity and hysteresis assessments; GS-4997/metabolite concentration vs. baseline-adjusted QTcF (DeltaQTcF) relationships were determined using linear mixed effects models. Bootstrapping was used to obtain 90% confidence intervals (CIs) of predicted placebo-corrected DeltaQTcF (DeltaDeltaQTcF). The upper bound of 90% CI for predicted DeltaDeltaQTcF was <10 msec at therapeutic and supratherapeutic GS-4997/metabolite levels, indicating the absence of a QT prolongation effect. Model performance/suitability was assessed using sensitivity/specificity analyses and diagnostic evaluations. This comprehensive methodology, supported by clinical pharmacology characteristics, was deemed adequate to assess the proarrhythmic risk of GS-4997/metabolite by the US Food and Drug Administration and European Medicines Agency resulting in a successful waiver from a dedicated thorough QT (TQT) study. PMID- 26259520 TI - Endowing a Content-Based Medical Image Retrieval System with Perceptual Similarity Using Ensemble Strategy. AB - Content-based medical image retrieval (CBMIR) is a powerful resource to improve differential computer-aided diagnosis. The major problem with CBMIR applications is the semantic gap, a situation in which the system does not follow the users' sense of similarity. This gap can be bridged by the adequate modeling of similarity queries, which ultimately depends on the combination of feature extractor methods and distance functions. In this study, such combinations are referred to as perceptual parameters, as they impact on how images are compared. In a CBMIR, the perceptual parameters must be manually set by the users, which imposes a heavy burden on the specialists; otherwise, the system will follow a predefined sense of similarity. This paper presents a novel approach to endow a CBMIR with a proper sense of similarity, in which the system defines the perceptual parameter depending on the query element. The method employs ensemble strategy, where an extreme learning machine acts as a meta-learner and identifies the most suitable perceptual parameter according to a given query image. This parameter defines the search space for the similarity query that retrieves the most similar images. An instance-based learning classifier labels the query image following the query result set. As the concept implementation, we integrated the approach into a mammogram CBMIR. For each query image, the resulting tool provided a complete second opinion, including lesion class, system certainty degree, and set of most similar images. Extensive experiments on a large mammogram dataset showed that our proposal achieved a hit ratio up to 10% higher than the traditional CBMIR approach without requiring external parameters from the users. Our database-driven solution was also up to 25% faster than content retrieval traditional approaches. PMID- 26259521 TI - Robust Automatic Pectoral Muscle Segmentation from Mammograms Using Texture Gradient and Euclidean Distance Regression. AB - In computer-aided diagnosis (CAD) of mediolateral oblique (MLO) view of mammogram, the accuracy of tissue segmentation highly depends on the exclusion of pectoral muscle. Robust methods for such exclusions are essential as the normal presence of pectoral muscle can bias the decision of CAD. In this paper, a novel texture gradient-based approach for automatic segmentation of pectoral muscle is proposed. The pectoral edge is initially approximated to a straight line by applying Hough transform on Probable Texture Gradient (PTG) map of the mammogram followed by block averaging with the aid of approximated line. Furthermore, a smooth pectoral muscle curve is achieved with proposed Euclidean Distance Regression (EDR) technique and polynomial modeling. The algorithm is robust to texture and overlapping fibro glandular tissues. The method is validated with 340 MLO views from three databases-including 200 randomly selected scanned film images from miniMIAS, 100 computed radiography images and 40 full-field digital mammogram images. Qualitatively, 96.75 % of the pectoral muscles are segmented with an acceptable pectoral score index. The proposed method not only outperforms state-of-the-art approaches but also accurately quantifies the pectoral edge. Thus, its high accuracy and relatively quick processing time clearly justify its suitability for CAD. PMID- 26259522 TI - An Investigation into the Consistency in Mammographic Density Identification by Radiologists: Effect of Radiologist Expertise and Mammographic Appearance. AB - The aim of this work is to investigate how radiologist expertise and image appearance may have an impact on inter-reader variability of mammographic density (MD) identification. Seventeen radiologists, divided into three expertise groups, were asked to manually segment the areas they consider to be MD in 40 clinical images. The variation in identification of MD for each image was quantified by finding the range of segmentation areas. The impact of radiologist expertise and image appearance on this variation was explored. The range of areas chosen by participating radiologists varied from 7 to 73% across the 40 images, with a mean range of 35 +/- 13%. Participants with high expertise were more likely to choose similar areas to one another, compared to participants with medium and low expertise levels (mean range were 19 +/- 10%, 29 +/- 13% and 25 +/- 14 %, respectively, p < 0.0001). There was a significantly higher average grey level for the area segmented by all radiologists as MD compared to the area of variation, with mean grey level value for 8-bit images being 146 +/- 19 vs. 99 +/ 14, respectively. MD segmentation borders were consistent in areas where there was a sharp intensity change within a short distance. In conclusion, radiologists with high expertise tend to have a higher agreement when identifying MD. Tissues which have a lower contrast and a less visually sharp gradient change at the interface between high density tissue and adipose background lead to inter-reader variation in choosing mammographic density. PMID- 26259523 TI - A multimodal disease modifying approach to treat neuropathic pain--inhibition of soluble epoxide hydrolase (sEH). AB - Both neuronal and non-neuronal mechanisms have been proposed to contribute to neuropathic pain (NP). All currently approved treatments for NP modulate neuronal targets and provide only symptomatic relief. Here we review evidence that inhibition of soluble epoxide hydrolase (sEH), the enzyme that degrades epoxyeicosatrienoic acids (EETs), has potential to be a multimodal, disease modifying approach to treat NP: (1) EET actions involve both endogenous opioid system and the GABAergic systems thus provide superior pain relief compared to morphine or gabapentin, (2) EETs are directly anti-inflammatory and inhibit expression of inflammatory cytokines and adhesion molecules thus can prevent continued nerve damage; and (3) EETs promote nerve regeneration in cultured neurons. Thus, an sEH inhibitor will not only provide effective pain relief, but would also block further nerve damage and promote healing. PMID- 26259524 TI - Birth order and risk of childhood cancer in the Danish birth cohort of 1973-2010. AB - PURPOSE: Many studies have investigated the possible association between birth order and risk of childhood cancer, although the evidence to date has been inconsistent. Birth order has been used as a marker for various in utero or childhood exposures and is relatively straightforward to assess. METHODS: Data were obtained on all children born in Denmark between 1973 and 2010, involving almost 2.5 million births and about 5,700 newly diagnosed childhood cancers before the age of 20 years. Data were analyzed using Poisson regression models. RESULTS: We failed to observe associations between birth order and risk of any childhood cancer subtype, including acute lymphoblastic leukemia; all rate ratios were close to one. Further analyses stratified by birth cohort (those born between 1973 and 1990, and those born between 1991 and 2010) also failed to show any associations. Considering stillbirths and/or controlling for birth weight and parental age in the analyses had no effect on the results. Analyses by years of birth (those born between 1973 and 1990, and those born between 1991 and 2010) did not show any changes in the overall pattern of no association. CONCLUSIONS: In this large cohort of all children born in Denmark over an almost 40-year period, we did not observe an association between birth order and the risk of childhood cancer. PMID- 26259528 TI - Relationships between immunoglobulin M and immunoglobulin G or A in colostrum of Japanese black multiparous cows. AB - This study was conducted to clarify the relationships among immunoglobulin (Ig)M, IgG, IgA, beta-carotene, vitamin A and alpha-tocopherol contents in colostrum of 24 Japanese Black multiparous cows in order to evaluate the role of IgM on colostral IgG and IgA production. Compared with colostral IgG, colostral IgM and IgA were very low but varied widely. There was positive correlation between colostral IgM and IgG, but colostral IgM was not related with colostral IgA. There was no relationship between colostral IgM and age of cows, although colostral IgG was increased with aging. There were positive correlations among colostral beta-carotene, vitamin A and alpha-tocopherol and these vitamins were positively correlated with colostral IgM and IgG. These results indicate that fat soluble vitamins may affect colostral IgG and IgM in cows and colostral IgG increases with the increase of colostral IgM. PMID- 26259529 TI - Acceptability of, and Information Needs Regarding, Next-Generation Sequencing in People Tested for Hereditary Cancer: A Qualitative Study. AB - Next generation sequencing (NGS) for patients at risk of hereditary cancer syndromes can also identify non-cancer related mutations, as well as variants of unknown significance. This study aimed to determine what benefits and shortcomings patients perceive in relation to NGS, as well as their interest and information preferences in regards to such testing. Eligible patients had previously received inconclusive results from clinical mutation testing for cancer susceptibility. Semi-structured telephone interviews were subjected to qualitative analysis guided by the approach developed by Miles and Huberman. The majority of the 19 participants reported they would be interested in panel/genomic testing. Advantages identified included that it would enable better preparation and allow implementation of individualized preventative strategies, with few disadvantages mentioned. Almost all participants said they would want all results, not just those related to their previous diagnosis. Participants felt that a face-to-face discussion supplemented by an information booklet would be the best way to convey information and achieve informed consent. All participants wanted their information stored and reviewed in accordance with new developments. Although the findings indicate strong interest among these individuals, it seems that the consent process, and the interpretation and communication of results will be areas that will require revision to meet the needs of patients. PMID- 26259530 TI - Parents' Experience with Pediatric Microarray: Transferrable Lessons in the Era of Genomic Counseling. AB - Advances in genome-based microarray and sequencing technologies hold tremendous promise for understanding, better-managing and/or preventing disease and disease related risk. Chromosome microarray technology (array based comparative genomic hybridization [aCGH]) is widely utilized in pediatric care to inform diagnostic etiology and medical management. Less clear is how parents experience and perceive the value of this technology. This study explored parents' experiences with aCGH in the pediatric setting, focusing on how they make meaning of various types of test results. We conducted in-person or telephone-based semi-structured interviews with parents of 21 children who underwent aCGH testing in 2010. Transcripts were coded and analyzed thematically according to the principles of interpretive description. We learned that parents expect genomic tests to be of personal use; their experiences with aCGH results characterize this use as intrinsic in the test's ability to provide a much sought-after answer for their child's condition, and instrumental in its ability to guide care, access to services, and family planning. In addition, parents experience uncertainty regardless of whether aCGH results are of pathogenic, uncertain, or benign significance; this triggers frustration, fear, and hope. Findings reported herein better characterize the notion of personal utility and highlight the pervasive nature of uncertainty in the context of genomic testing. Empiric research that links pre-test counseling content and psychosocial outcomes is warranted to optimize patient care. PMID- 26259531 TI - Leukemia Relapse-Associated Mutation of NT5C2 Gene is Rare in de Novo Acute Leukemias and Solid Tumors. PMID- 26259532 TI - Genetic Alterations in Hungarian Patients with Papillary Thyroid Cancer. AB - The incidence of thyroid cancers is increasing worldwide. Some somatic oncogene mutations (BRAF, NRAS, HRAS, KRAS) as well as gene translocations (RET/PTC, PAX8/PPAR-gamma) have been associated with the development of thyroid cancer. In our study, we analyzed these genetic alterations in 394 thyroid tissue samples (197 papillary carcinomas and 197 healthy). The somatic mutations and translocations were detected by Light Cycler melting method and Real-Time Polymerase Chain Reaction techniques, respectively. In tumorous samples, 86 BRAF (44.2%), 5 NRAS (3.1%), 2 HRAS (1.0%) and 1 KRAS (0.5%) mutations were found, as well as 9 RET/PTC1 (4.6%) and 1 RET/PTC3 (0.5%) translocations. No genetic alteration was seen in the non tumorous control thyroid tissues. No correlation was detected between the genetic variants and the pathological subtypes of papillary cancer as well as the severity of the disease. Our results are only partly concordant with the data found in the literature. PMID- 26259533 TI - SINEUPs: A new class of natural and synthetic antisense long non-coding RNAs that activate translation. AB - Over the past 10 years, it has emerged that pervasive transcription in mammalian genomes has a tremendous impact on several biological functions. Most of transcribed RNAs are lncRNAs and repetitive elements. In this review, we will detail the discovery of a new functional class of natural and synthetic antisense lncRNAs that stimulate translation of sense mRNAs. These molecules have been named SINEUPs since their function requires the activity of an embedded inverted SINEB2 sequence to UP-regulate translation. Natural SINEUPs suggest that embedded Transposable Elements may represent functional domains in long non-coding RNAs. Synthetic SINEUPs may be designed by targeting the antisense sequence to the mRNA of choice representing the first scalable tool to increase protein synthesis of potentially any gene of interest. We will discuss potential applications of SINEUP technology in the field of molecular biology experiments, in protein manufacturing as well as in therapy of haploinsufficiencies. PMID- 26259534 TI - Premature termination of GAT1 transcription explains paradoxical negative correlation between nitrogen-responsive mRNA, but constitutive low-level protein production. AB - The first step in executing the genetic program of a cell is production of mRNA. In yeast, almost every gene is transcribed as multiple distinct isoforms, differing at their 5' and/or 3' termini. However, the implications and functional significance of the transcriptome-wide diversity of mRNA termini remains largely unexplored. In this paper, we show that the GAT1 gene, encoding a transcriptional activator of nitrogen-responsive catabolic genes, produces a variety of mRNAs differing in their 5' and 3' termini. Alternative transcription initiation leads to the constitutive, low level production of 2 full length proteins differing in their N-termini, whereas premature transcriptional termination generates a short, highly nitrogen catabolite repression- (NCR-) sensitive transcript that, as far as we can determine, is not translated under the growth conditions we used, but rather likely protects the cell from excess Gat1. PMID- 26259535 TI - Altering histone acetylation status in donor cells with suberoylanilide hydroxamic acid does not affect dog cloning efficiency. AB - Although dog cloning technology has been applied to conservation of endangered canids, propagation of elite dogs, and production of transgenic dogs, the efficiency of cloning is still very low. To help overcome this problem, we evaluated the effect of treating donor cells with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, on dog cloning efficiency. Relative messenger RNA expressions of the bax1/bcl2 ratio and Dnmt1 in fibroblasts treated with different concentrations (0, 1, 10, 50 MUM) of SAHA and durations (0, 20, 44 hours) were compared. Treatment with 1 MUM for 20 hours showed significantly lower bax1/bcl2 and Dnmt1 transcript abundance. Acetylation of H3K9 was significantly increased after SAHA treatment, but H4K5, H4K8 and H4K16 were not changed. After SCNT using control or donor cells treated with SAHA, a total of 76 and 64 cloned embryos were transferred to seven and five recipients, respectively. Three fetuses were diagnosed in both control and SAHA-treated groups by ultrasonography 29 days after the embryo transfer, but there was no significant difference in the pregnancy rate (4.2% vs. 4.3%). In conclusion, although SAHA treatment as used in this study significantly decreased bax1/bcl2 and Dnmt1 transcripts of donor nuclei, as well as increased H3 acetylation, it was not enough to increase in vivo developmental competence of cloned dog embryos. PMID- 26259536 TI - The role of diet and housing-temperature in the production of genetically modified mouse embryos and their developmental capacity after cryopreservation. AB - Mutant mouse lines are unique models with an enormous scientific potential. Cryopreservation of preimplantation embryos or of spermatozoa is a common approach to save those lines. The breeding of a line can be discontinued if sufficient specimens have been cryopreserved. Prerequisites to economically cryopreserve embryos are high yields of embryos prepared from donors and a high recovery rate after revitalization. Diets for laboratory animals are often produced from phytoestrogen-containing soy; the present study shows that feeding the donor animals with a phytoestrogen-poor diet is more efficient compared to a phytoestrogen-containing, soy-based diet. Additionally, a uterotrophic bioassay indicating the estrogenic role of compounds showed a significant increase of the relative uterus size of females fed with a phytoestrogen-rich diet. The role of the housing-temperature was investigated, too, showing that a housing-temperature of 24 degrees C results in the best embryo yields. The production of two-cell embryos is more economic than the production of eight-cell embryos. Investigating the recovery rate of frozen/thawed embryos, a very high recovery rate was determined when both, two- and eight-cell embryos were thawed. However, the capacity to develop to the next embryonic stage in vitro was dramatically reduced when two-cell embryos were compared to eight-cell embryos. After embryo transfer, the sex ratio became uneven and more males were delivered. This effect might be due to the procedures to which animals and embryos were subjected. These data show that many parameters can influence the production of animals when using (frozen/thawed) embryos. These parameters need continuous surveillance. PMID- 26259537 TI - Is miR-34a a Well-equipped Swordsman to Conquer Temple of Molecular Oncology? AB - Overwhelmingly increasing advancements in miRNA biology have opened new avenues for pharmaceutical companies to initiate studies on designing effective, safe, and therapeutically active candidates using miRNA mimetics and miRNA inhibitors. In accordance with this approach, development of miravirsen and SPC3649, an LNA based (locked nucleic acid) antisense molecule against miR-122, to treat hepatitis C has sparked interest in identifying most efficient microRNAs for journey from bench-top toward pharmaceutical industry and breakthroughs in delivery technology will pave the way to 'final frontier'. MRX34, a liposome formulated mimic of miR-34 for treatment of metastatic cancer with liver involvement and unresectable primary liver cancer, has also entered in clinical trial. There is a successive increase in the research work related to miR-34 biology and miRNA regulation of modulators of intracellular signaling cascades. We partition this review into how miR-34a is regulated by different proteins and how Wnt- and TGF-induced intracellular signaling cascades are modulated by miR 34a. In this review, we bring to limelight how miR-34a regulates its target genes to induce apoptosis and inhibit cell proliferation as evidenced by in vitro and in vivo analysis. We also discuss miR-34 regulation of PDGFR and c-MET and recent advancements in nanotechnologically delivered miR-34a. Spotlight is also set on modulation of chemotherapeutic sensitivity by miR-34a in cancer cells using reconstruction studies. Clinical trial of miR-34 is indicative of its tremendous potential, and continuous cutting research will prove to be effective in efficiently translating laboratory findings into clinically effective therapeutics. PMID- 26259538 TI - Puberty onset is delayed following uteroplacental insufficiency and occurs earlier with improved lactation and growth for pups born small. AB - Being born small programs adult diseases later in life, with the early postnatal growth rate in growth-restricted offspring playing a role in the reduction of the risk of disease in adulthood. In addition, early postnatal growth is critical for puberty onset (PO). Using cross-fostering, we determined the effects of growth restriction and prenatal and postnatal environments on PO and sex steroids. Bilateral uterine vessel ligation (Restricted) or sham surgery (Control), performed on Gestational Day 18 in Wistar-Kyoto rats induced fetal growth restriction. Control, Reduced (Control litter size reduced to five pups) and Restricted pups were cross-fostered onto different Control (normal lactation) or Restricted (impaired lactation) mothers on Day 1. The day of vaginal opening (females) and balanopreputial separation (males) characterised PO. Blood was sampled for sex steroid and leptin analysis. Restricted pups were born lighter than Controls (P<0.05). PO was delayed by 3.4-4 days in Restricted-on-Restricted males and females (P<0.05). Plasma leptin concentrations at PO were lower in both sexes in all groups compared with Restricted-on-Control and Control-on-Control (P<0.05). PO occurred earlier in Restricted-on-Control (~2 days) with normal leptin concentrations and accelerated growth compared with Restricted-on Restricted (P<0.05). Testosterone concentrations were lower in male Restricted-on Restricted than Control-on-Control at 6 months (P<0.05). Restricted-on-Restricted females had lower progesterone at PO compared with Control-on-Control (P<0.05). Female Restricted-on-Restricted had lower oestradiol, with Restricted-on-Control having higher testosterone concentrations at 6 months than Control-on-Control (P<0.05). Growth restriction reduced postnatal growth and leptin concentrations, delaying PO in both sexes and programming altered sex steroids. This highlights the importance of the interaction between prenatal and postnatal growth in the programming of adult reproductive status. PMID- 26259539 TI - Mesoscale Characterization of Nanoparticles Distribution Using X-ray Scattering. AB - The properties of many functional materials depend critically on the spatial distribution of an active phase within a support. In the case of solid catalysts, controlling the spatial distribution of metal (oxide) nanoparticles at the mesoscopic scale offers new strategies to tune their performance and enhance their lifetimes. However, such advanced control requires suitable characterization methods, which are currently scarce. Here, we show how the background in small-angle X-ray scattering patterns can be analyzed to quantitatively access the mesoscale distribution of nanoparticles within supports displaying hierarchical porosity. This is illustrated for copper catalysts supported on meso- and microporous silica displaying distinctly different metal distributions. Results derived from X-ray scattering are in excellent agreement with electron tomography. Our strategy opens unprecedented prospects for understanding the properties and to guide the synthesis of a wide array of functional nanomaterials. PMID- 26259540 TI - Heart mitochondria and calpain 1: Location, function, and targets. AB - Calpain 1 is an ubiquitous Ca(2+)-dependent cysteine protease. Although calpain 1 has been found in cardiac mitochondria, the exact location within mitochondrial compartments and its function remain unclear. The aim of the current review is to discuss the localization of calpain 1 in different mitochondrial compartments in relationship to its function, especially in pathophysiological conditions. Briefly, mitochondrial calpain 1 (mit-CPN1) is located within the intermembrane space and mitochondrial matrix. Activation of the mit-CPN1 within intermembrane space cleaves apoptosis inducing factor (AIF), whereas the activated mit-CPN1 within matrix cleaves complex I subunits and metabolic enzymes. Inhibition of the mit-CPN1 could be a potential strategy to decrease cardiac injury during ischemia reperfusion. PMID- 26259541 TI - Initiation & completion rates of hepatitis A vaccination among US pediatric populations born between 2005 and 2009. AB - OBJECTIVES: To estimate hepatitis A vaccine series initiation and completion rates, assess time to vaccination, identify missed opportunities for the hepatitis A vaccine series, and examine factors associated with hepatitis A vaccine series initiation and completion. METHODS: We conducted a retrospective, observational study using three healthcare claims databases separately. The study population was comprised of children born between years 2005 and 2009 that were continuously enrolled for at least three and a half years from the date of birth. Every child was followed from date of birth for three and a half years for hepatitis A vaccination. RESULTS: There were 93,735 eligible children from Clinformatics Data Mart, 202,513 from MarketScan Commercial, and 207,545 from MarketScan Medicaid. The overall hepatitis A vaccine series initiation rate was 63.8-79.4% and completion rate was 45.1-66.8% across the three databases. About 62.8-90.1% of the children who never initiated hepatitis A vaccine had at least one well visit from 1 year to three and a half years old. Children were more likely to initiate and complete the hepatitis A vaccine series if they were from more recent birth cohorts, from states with a hepatitis A vaccination recommendation prior to the ACIP universal recommendation, from states with daycare/school entry requirements, were enrolled in an HMO health plan, had pediatricians as primary providers, had more doctor's office/well visits and received MMR/Varicella vaccines. CONCLUSION: In this study, approximately one in every three to five children remained unvaccinated against hepatitis A. Although the hepatitis A vaccine series initiation and completion improved from 2005 to 2009, vaccine coverage has stabilized in recent years. It is important for providers to identify every opportunity for hepatitis A vaccination and to assure that children get protection from this vaccine-preventable disease. PMID- 26259542 TI - Delayed BCG vaccination results in minimal alterations in T cell immunogenicity of acellular pertussis and tetanus immunizations in HIV-exposed infants. AB - BACKGROUND: Bacille Calmette-Guerin (BCG) is effective in preventing disseminated tuberculosis (TB) in children but may also have non-specific benefits, and is thought to improve immunity to unrelated antigens through trained innate immunity. In HIV-infected infants, there is a risk of BCG-associated adverse events. We aimed to explore whether delaying BCG vaccination by 8 weeks, in utero or perinatal HIV infection is excluded, affected T-cell responses to B. pertussis (BP) and tetanus toxoid (TT), in HIV-exposed, uninfected infants. METHODS: Infants were randomized to receive BCG vaccination at birth or 8 weeks of age. At 8 and 14 weeks, T cell proliferation and intracellular cytokine (IL-2, IL-13, IL 17, and IFN-gamma) expression was analyzed in response to BP, TT and Staphylococcal enterotoxin B (SEB) antigens. RESULTS: Delaying BCG vaccination did not alter T-cell proliferation to BP or TT antigens. Infants immunized with BCG at birth had higher CD4+ T cell proliferation to SEB at 14 weeks of age (p=0.018). Birth-vaccinated infants had increased CD8+ IL-2 expression in response to BP, but not TT or SEB, at 8 weeks. Infants vaccinated with BCG at 8 weeks had significantly lower IL-13 expression by BP-specific CD4+ and CD8+ T cells at 14 weeks (p=0.032 and p=0.0035, respectively). There were no observed differences in multifunctional cytokine response to TT, BP or SEB between infants vaccinated with BCG at birth versus 8 weeks of age. CONCLUSION: Delaying BCG vaccination until 8 weeks of age results in robust T-cellular responses to BP and TT in HIV-exposed infants. CLINICAL TRIAL REGISTRY: NCT02062580. PMID- 26259543 TI - Expression of enhancing-activity-free neutralizing antibody against dengue type 1 virus in plasmid-inoculated mice. AB - BACKGROUND: Most candidate dengue vaccines currently under development induce neutralizing antibodies, which are considered important for immunoprotection. However, the concomitant induction of infection-enhancing antibodies is an unavoidable concern. In contrast, a neutralizing antibody developed for passive immunotherapy has been engineered to eliminate its enhancing activity. Therefore, a strategy for the long-term expression of enhancing-activity-free neutralizing antibodies may resolve this concern. METHODS: A mouse monoclonal antibody, 7F4, of the IgG3 subclass and with no detectable enhancing activity, was selected as the model neutralizing antibody to evaluate the potential of this strategy. Equal amounts of commercial vector (pFUSE)-based plasmids containing 7F4 heavy (H)- or light (L)-chain variable region genes were mixed and used for the cotransfection of 293T cells and co-delivery into ICR and BALB/c mice. The recombinant plasmids were designed to express IgG2b or IgG3 subclass antibodies (p7F4G2b or p7F4G3, respectively). RESULTS: 293T cells transfected with 2 MUg of p7F4G2b or p7F4G3 produced approximately 15,000 or 800 ng/ml IgG in the culture fluids, respectively. The dose is expressed as the total amount of H- and L-chain plasmids. Neutralizing antibody was detected dose-dependently in ICR mice inoculated with 50-200 MUg of p7F4G2b. A 1:2 dilution of sera from ICR and BALB/c mice inoculated with 100 MUg of p7F4G3 showed average plaque reduction levels of >70% on day 3 and >90% on days 5-9. BALB/c mice maintained detectable neutralizing antibody for at least 3 months. The neutralizing antibody expressed by p7F4G3 in mice showed no enhancing activity. DISCUSSION: Although the expression of neutralizing antibodies from immunoglobulin genes is a type of passive immunization, its durability can be utilized as a dengue vaccine strategy. This "proof-of-concept" study using a mouse model demonstrates that the enhancing-activity-free characteristic of this strategy augurs well for dengue vaccine development, although further improvement is required. PMID- 26259544 TI - Mapping Mechanical Force Propagation through Biomolecular Complexes. AB - Here we employ single-molecule force spectroscopy with an atomic force microscope (AFM) and steered molecular dynamics (SMD) simulations to reveal force propagation pathways through a mechanically ultrastable multidomain cellulosome protein complex. We demonstrate a new combination of network-based correlation analysis supported by AFM directional pulling experiments, which allowed us to visualize stiff paths through the protein complex along which force is transmitted. The results implicate specific force-propagation routes nonparallel to the pulling axis that are advantageous for achieving high dissociation forces. PMID- 26259545 TI - Description of Dichelacera (Dichelacera) walteri n. sp. (Diptera: Tabanidae) with a Key to Related Species in the Subgenus Dichelacera Macquart. AB - Dichelacera (Dichelacera) walteri Guimaraes, Gorayeb & Rodrigues-Guimaraes n. sp. is described from female specimens collected in Marambaia Island, located in Mangaratiba County, state of Rio de Janeiro, Brazil. The characterization of the species was based in the following characters: a medium-sized species, more sclerotized than others in the subgenus Dichelacera Macquart, the second segment of palp with dark setae and longer than the third antennal segment, a brown scutum with pruinescence on the anterior half and posterior edges with white tonality, yellow dorsum of abdomen with the last three segments brown, white yellowish venter with yellow setae, narrow frons with dark brown callus, extending just beyond a ridge in the middle of the frons, vertex with ocelli, hyaline wings with three large black bands, and tricolored legs. PMID- 26259546 TI - Muscle Metabolic Responses During Dynamic In-Magnet Exercise Testing: A Pilot Study in Children with an Idiopathic Inflammatory Myopathy. AB - RATIONALE AND OBJECTIVES: The clinical utility of supine in-magnet bicycling in combination with phosphorus magnetic resonance spectroscopy ((31)P MRS) to evaluate quadriceps muscle metabolism was examined in four children with juvenile dermatomyositis (JDM) in remission and healthy age- and gender-matched controls. MATERIALS AND METHODS: Two identical maximal supine bicycling tests were performed using a magnetic resonance-compatible ergometer. During the first test, cardiopulmonary performance was established in the exercise laboratory. During the second test, quadriceps energy balance and acid/base balance during incremental exercise and phosphocreatine recovery were determined using (31)P MRS. RESULTS: During the first test, no significant differences were found between patients with JDM and their healthy peers regarding cardiopulmonary performance. The outcomes of the first test indicate that both groups attained maximal performance. During the second test, quadriceps phosphocreatine and pH time courses were similar in all but one patient experiencing idiopathic postexercise pain. This patient demonstrated faster phosphocreatine depletion and acidification during exercise, yet postexercise mitochondrial adenosine triphosphate synthesis rate measured by phosphocreatine recovery kinetics was approximately twofold faster than control (time constant 23 seconds vs 43 +/- 7 seconds, respectively). CONCLUSIONS: These results highlight the utility of in magnet cycle ergometry in combination with (31)P MRS to assess and monitor muscle energetic patterns in pediatric patients with inflammatory myopathies. PMID- 26259547 TI - Capricorn-A Web-Based Automatic Case Log and Volume Analytics for Diagnostic Radiology Residents. AB - RATIONALE AND OBJECTIVES: On-service clinical learning is a mainstay of radiology education. However, an accurate and timely case log is difficult to keep, especially in the absence of software tools tailored to resident education. Furthermore, volume-related feedback from the residency program sometimes occurs months after a rotation ends, limiting the opportunity for meaningful intervention. MATERIALS AND METHODS: We surveyed the residents of a single academic institution to evaluate the current state of and the existing need for tracking interpretation volume. Using the results of the survey, we created an open-source automated case log software. Finally, we evaluated the effect of the software tool on the residency in a 1-month, postimplementation survey. RESULTS: Before implementation of the system, 89% of respondents stated that volume is an important component of training, but 71% stated that volume data was inconvenient to obtain. Although the residency program provides semiannual reviews, 90% preferred reviewing interpretation volumes at least once monthly. After implementation, 95% of the respondents stated that the software is convenient to access, 75% found it useful, and 88% stated they would use the software at least once a month. The included analytics module, which benchmarks the user using historical aggregate average volumes, is the most often used feature of the software. Server log demonstrates that, on average, residents use the system approximately twice a week. CONCLUSIONS: An automated case log software system may fulfill a previously unmet need in diagnostic radiology training, making accurate and timely review of volume-related performance analytics a convenient process. PMID- 26259548 TI - Needs Assessment for Standardized Medical Student Imaging Education: Review of the Literature and a Survey of Deans and Chairs. AB - RATIONALE AND OBJECTIVES: Medical imaging education often has limited representation in formal medical student curricula. Although the need for greater inclusion of radiology material is generally agreed on, the exact skillset that should be taught is less clear. The purpose of our study was to perform a needs assessment for a national radiology curriculum for medical students. MATERIALS AND METHODS: We analyzed data from previous unpublished portions of the American College of Radiology/Alliance of Medical Student Educators in Radiology survey of Deans and Radiology Chairs regarding prevalence of radiology curricular revisions, assessment tools, use of the American College of Radiology Appropriateness Criteria, and resources used in curriculum revision. We also performed a literature search through both PubMED and a general search engine (Google) to identify available resources for designing and implementing imaging curricula and curricular revisions. RESULTS: Medical school deans and chairs reported a need for more overall radiology content; one of every six programs (15%) reported they had no recognized imaging curriculum. Of schools currently with imaging curricula, 82% have undergone revision in the last 10 years using a variety of different resources, but there is no universally agreed on guide or standard curriculum. The PubMED and Google searches identified only 23 and eight resources, respectively, suggesting a sizable deficit in available guidance; however, a single published medical student radiology curriculum is available through the Alliance of Medical Student Educators in Radiology. CONCLUSIONS: There is a need, but few available resources, to guide educators in adding imaging content to medical school curricula. We postulate that a standardized national curriculum directed by a focused skillset may be useful to educators and could result in greater uniformity of imaging skills among graduating US medical students. A proposed skillset to guide a national curriculum in radiology is described. PMID- 26259549 TI - Twelve-Hour Hypothermic Machine Perfusion for Donor Heart Preservation Leads to Improved Ultrastructural Characteristics Compared to Conventional Cold Storage. AB - BACKGROUND Hypothermic machine perfusion of donor hearts has the theoretical advantage of continuous aerobic metabolism and washes out toxic metabolic byproducts. Here, we studied the effect of hypothermic machine perfusion on cardiac myocyte integrity when hearts are preserved for longer ischemic times (12 hours). MATERIAL AND METHODS Pig hearts were harvested and stored in Celsior(r) solution for 12 hours using either conventional cold storage on ice (12 h CS, n=3) or pulsatile perfusion with the Paragonix Sherpa PerfusionTM Cardiac Transport System at different flow rates (12 h PP, n=3 or 12 h PP low flow, n=2). After cold preservation, hearts were reperfused using an LV isovolumic Langendorff system. Controls (n=3) were reperfused immediately after organ harvest. Biopsies were taken from the apex of the left ventricle before storage, after storage and after reperfusion to measure ATP and endothelin-1 content in the tissue. TUNEL staining for signs of apoptosis and electron microscopy of the donor hearts were performed. RESULTS 12 h PP hearts showed significantly more weight gain than 12 h CS and controls after preservation. Pulsatile perfused hearts showed less ATP depletion, lower endothelin-1 levels and less apoptosis after preservation compared to CS. Electron microscopy showed damaged muscle fibers, endothelial cell rupture, and injury of mitochondria in the 12 h CS group, while machine perfusion could preserve the cell structures. CONCLUSIONS Hypothermic machine perfusion of donor hearts can preserve the cell structures better than conventional cold storage in prolonged ischemic times. Hypothermic pulsatile perfusion may therefore enable longer preservation times of donor hearts. Whether this method is able to avoid primary graft failure after orthotopic heart transplantation remains to be evaluated in further studies. PMID- 26259550 TI - Environmental attributable fractions in remote Australia: the potential of a new approach for local public health action. AB - OBJECTIVES: To determine local values for environmental attributable fractions and explore their applicability and potential for public health advocacy. METHODS: Using World Health Organization (WHO) values for environmental attributable fractions, responses from a practitioner survey (73% response rate) were considered by a smaller skills-based panel to determine consensus values for Kimberley environmental attributable fractions (KEAFs). Applied to de-identified data from 17 remote primary healthcare facilities over two years, numbers and proportions of reasons for attendance directly attributable to the environment were calculated for all ages and children aged 0-4 years, including those for Aboriginal patients. RESULTS: Of 150,357 reasons for attendance for patients of all ages, 31,775 (21.1%) were directly attributable to the environment. The proportion of these directly due to the environment was significantly higher for Aboriginal patients than others (23.1% v 14.6%; p<0.001). Of 29,706 reasons for attendance by Aboriginal children aged 0-4 years, 7,599 (25.6%) were directly attributable to the environment, significantly higher than for non-Aboriginal children aged 0-4 years (25.6% v 18.6%; p<0.001). CONCLUSIONS: By addressing environmental factors, 20% of total primary healthcare demand could be prevented and, importantly, some 25% of presentations by Aboriginal children. IMPLICATIONS: KEAFs have potential to monitor impact of local environmental investments. PMID- 26259551 TI - Motor learning strategies in basketball players and its implications for ACL injury prevention: a randomized controlled trial. AB - PURPOSE: Adding external focus of attention (EF, focus on the movement effect) may optimize current anterior cruciate ligament (ACL) injury prevention programmes. The purpose of the current study was to investigate the effects of an EF, by a visual stimulus and an internal focus, by a verbal stimulus during unexpected sidestep cutting in female and male athletes and how these effects remained over time. METHODS: Ninety experienced basketball athletes performed sidestep cutting manoeuvres in three sessions (S1, S2 and S3). In this randomized controlled trial, athletes were allocated to three groups: visual (VIS), verbal (VER) and control (CTRL). Kinematics and kinetics were collected at the time of peak knee frontal plane moment. RESULTS: Males in the VIS group showed a larger vertical ground reaction force (S1: 25.4 +/- 3.1 N/kg, S2: 25.8 +/- 2.9 N/kg, S3: 25.2 +/- 3.2 N/kg) and knee flexion moments (S1: -3.8 +/- 0.9 Nm/kg, S2: -4.0 +/- 1.2 Nm/kg, S3: -3.9 +/- 1.3 Nm/kg) compared to the males in the VER and CTRL groups and to the females in the VIS group (p < 0.05). Additionally, the males in the VIS group reduced knee valgus moment and the females in the VER group reduced knee varus moment over time (n.s.). CONCLUSION: Male subjects clearly benefit from visual feedback. Females may need different feedback modes to learn a correct movement pattern. Sex-specific learning preferences may have to be acknowledged in day by day practice. Adding video instruction or feedback to regular training regimens when teaching athletes safe movement patterns and providing individual feedback might target suboptimal long-term results and optimize ACL injury prevention programmes. LEVEL OF EVIDENCE: I. PMID- 26259552 TI - Reliability of Assessing Hand Osteoarthritis on Digital Photographs and Associations With Radiographic and Clinical Findings. AB - OBJECTIVE: To investigate the reliability and construct validity of an atlas for grading hand osteoarthritis (OA) on photographs in a separate younger community dwelling population than the development cohort. METHODS: Participants were community-dwelling adults (ages >=50 years) in North Staffordshire, UK with hand pain or hand problems in the last year who attended a research clinic. High quality photographs were taken in a standardized position. A photographic atlas was used to score hand joints (second and third distal interphalangeal [DIP], second and third proximal interphalangeal [PIP], and first carpometacarpal [CMC] joints) and joint groups (DIP, PIP, and CMC joints) for OA on a 0-3 scale. Hand radiographs were graded for OA using the Kellgren/Lawrence (K/L) grading system. Clinical features (nodes, bony enlargement, and deformity) were determined by physical examination. Associations of photographic hand OA grades with radiographic OA and clinical features were determined to assess construct validity. RESULTS: In total, 558 participants (mean age 64 years, 62% women) were included in the analyses. Reliability for scoring OA on the photographs was good (mean intrarater intraclass correlation coefficient [ICC] 0.77 and mean interrater ICC 0.71). At the joint level, photographic hand OA grade was positively associated with radiographic OA grade (Spearman's rho = 0.19-0.57, P < 0.001) and the number of clinical features (Spearman's rho = 0.36-0.59, P < 0.001). At the person level, individuals with higher global photographic OA scores had higher summed K/L scores and higher percentages meeting the American College of Rheumatology clinical hand OA criteria. CONCLUSION: This photographic scoring system was reliable and a good indicator of hand OA in a separate younger community-dwelling population than the development cohort. This method of data collection offers researchers a feasible alternative to physical examination and radiography. PMID- 26259553 TI - Chemical chaperone treatment for galactosialidosis: Effect of NOEV on beta galactosidase activities in fibroblasts. AB - INTRODUCTION: Galactosialidosis is a rare lysosomal storage disease caused by a combined deficiency of GM1 beta-galactosidase (beta-gal) and neuraminidase secondary to a defect of a lysosomal enzyme protective protein/cathepsin A (PPCA) and mutation in CTSA gene. Three subtypes are recognized: early infantile, late infantile, and juvenile/adult. There is no specific therapy for patients with galactosialidosis at this time. OBJECTIVES: The aim of this study was to determine the chaperone effect of N-octyl-4-epi-beta-valienamine (NOEV) on beta gal proteins in skin fibroblasts of PPCA-deficit patients. METHODS: beta-Gal and neuraminidase activities were measured for the diagnosis of the patients with galactosialidosis. Western blotting for PPCA protein and direct sequencing for CTSA gene were performed. Cultured skin fibroblast were treated with NOEV. RESULTS: We report four novel patients with galactosialidosis: one had the early infantile form and the other three had the juvenile/adult form. We found that NOEV stabilized beta-gal activity in lysate from cultured skin fibroblasts from these patients. Treatment with NOEV significantly enhanced beta-gal activity in cultured skin fibroblasts in the absence of PPCA. CONCLUSIONS: Our results indicate the possibility that NOEV chaperone therapy might have a beneficial effect, at least in part, for patients with galactosialidosis. PMID- 26259555 TI - Scale-dependency of the global mean surface temperature trend and its implication for the recent hiatus of global warming. AB - Studies of the global mean surface temperature trend are typically conducted at a single (usually annual or decadal) time scale. The used scale does not necessarily correspond to the intrinsic scales of the natural temperature variability. This scale mismatch complicates the separation of externally forced temperature trends from natural temperature fluctuations. The hiatus of global warming since 1999 has been claimed to show that human activities play only a minor role in global warming. Most likely this claim is wrong due to the inadequate consideration of the scale-dependency in the global surface temperature (GST) evolution. Here we show that the variability and trend of the global mean surface temperature anomalies (GSTA) from January 1850 to December 2013, which incorporate both land and sea surface data, is scale-dependent and that the recent hiatus of global warming is mainly related to natural long-term oscillations. These results provide a possible explanation of the recent hiatus of global warming and suggest that the hiatus is only temporary. PMID- 26259554 TI - A fluoroscopy-based planning and guidance software tool for minimally invasive hip refixation by cement injection. AB - PURPOSE: In orthopaedics, minimally invasive injection of bone cement is an established technique. We present HipRFX, a software tool for planning and guiding a cement injection procedure for stabilizing a loosening hip prosthesis. HipRFX works by analysing a pre-operative CT and intraoperative C-arm fluoroscopic images. METHODS: HipRFX simulates the intraoperative fluoroscopic views that a surgeon would see on a display panel. Structures are rendered by modelling their X-ray attenuation. These are then compared to actual fluoroscopic images which allow cement volumes to be estimated. Five human cadaver legs were used to validate the software in conjunction with real percutaneous cement injection into artificially created periprothetic lesions. RESULTS: Based on intraoperatively obtained fluoroscopic images, our software was able to estimate the cement volume that reached the pre-operatively planned targets. The actual median target lesion volume was 3.58 ml (range 3.17-4.64 ml). The median error in computed cement filling, as a percentage of target volume, was 5.3% (range 2.2 14.8%). Cement filling was between 17.6 and 55.4% (median 51.8%). CONCLUSIONS: As a proof of concept, HipRFX was capable of simulating intraoperative fluoroscopic C-arm images. Furthermore, it provided estimates of the fraction of injected cement deposited at its intended target location, as opposed to cement that leaked away. This level of knowledge is usually unavailable to the surgeon viewing a fluoroscopic image and may aid in evaluating the success of a percutaneous cement injection intervention. PMID- 26259556 TI - Long-term outcomes of operative versus nonoperative treatment for uncomplicated appendicitis. AB - PURPOSE: Although nonoperative treatment for uncomplicated appendicitis is now an accepted approach, there are few reports in children. The aim of this study was to compare long-term outcomes between operative and nonoperative treatment in children. METHODS: Between April 2007 and December 2013, all uncomplicated appendicitis patients were asked to select either operative (laparoscopic surgery) or nonoperative treatment on admission. For nonoperative treatment, intravenous injection of antibiotics was continued until serum C-reactive protein concentration decreased to below 0.5mg/dL. A questionnaire survey on satisfaction with treatment was added afterwards and performed more than 1year after treatment. RESULTS: Eighty-six patients chose operative treatment, and 78 chose nonoperative treatment. The success rate of nonoperative treatment was 98.7%. There was no difference in the length of hospital stay between the two groups. Ileus occurred in two operatively-treated patients, while recurrence of appendicitis occurred in 22 nonoperatively-treated patients (28.6 %) after an average of 4.3years of follow-up. The overall nonoperative treatment failure including both early failure and recurrence occurred more frequently among those with appendicoliths than without appendicoliths. Satisfaction levels were higher for operative treatment. CONCLUSIONS: Although the success rate of nonoperative treatment was very high, a considerable number of patients experienced recurrence. PMID- 26259557 TI - Carcinoid tumours of the appendix in children having appendicectomies at Princess Margaret Hospital since 1995. AB - AIM: The diagnosis of carcinoid tumour is a relatively rare one. Our surgical approach has changed over the last two decades from predominantly open to predominately laparoscopic with a tendency to leave the mesoappendix in situ. The aim of this audit was to identify how many cases we had at PMH and to see whether the shift in surgical approach allowed us to make prognostic decisions in keeping with current best practice and whether this made any difference in further surgery requirements or outcome for patients. METHODS: A retrospective review of all cases of carcinoid identified in our search of all appendicectomy histopathology results was conducted. Results were compared to those found in other studies. Duration of follow up and further investigations was reviewed, as was whether or not there was any recurrence. RESULTS: Our incidence of carcinoid tumours in patients undergoing appendicectomy since 1995 was 0.35%, similar to that in other centres. None of our patients had surgery beyond an appendicectomy and our active follow up varied from none to 6 months. There were no recurrences in this time. CONCLUSIONS: The literature review carried out suggests further meta-analysis is needed including data on long term follow up before definitive guidelines regarding extent of surgical treatment and follow up based on histopathology are created. The condition is rare and the studies small, resulting in no clear consensus on the best practice for tumours measuring between 1 and 1.5 cm in diameter. Our surgical approach to appendicectomies has changed; it is unclear whether this has resulted in a change in outcome. PMID- 26259558 TI - Malformations associated with congenital diaphragmatic hernia: Impact on survival. AB - BACKGROUND/PURPOSE: Congenital diaphragmatic hernia (CDH) is associated with high mortality. Survival is influenced by the extent of pulmonary hypoplasia and additional congenital defects. The purpose of this study was to assess the association of congenital anomalies and admission capillary carbon dioxide levels (PcCO2), as a measure of extent of pulmonary hypoplasia, on survival in neonates with CDH. METHODS: This is a retrospective review of neonates with CDH admitted to a tertiary neonatal intensive care unit between 1990 and 2014. Logistic regression was used to assess whether hospital survival was associated with admission PcCO2 or associated anomalies (isolated CDH, CDH with cardiovascular anomalies, and CDH with noncardiac anomalies). The probabilities of survival (POS) score, based on birth weight and 5-min Apgar as defined by the Congenital Diaphragmatic Hernia Study Group were included as a covariate. RESULTS: Of 97 patients, 55 had additional malformations (cardiovascular n=12, noncardiac anomalies n=43). POS was lower in CDH with other anomalies compared to isolated CDH. Survival rate was 61.9%, 53.5% and 41.7% in isolated CDH, CDH with noncardiac anomalies and CDH with cardiovascular anomalies, respectively. After adjusting for POS score the likelihood of survival in CDH groups with additional anomalies was similar to isolated CDH (OR 0.95, 95% CI 0.22-4.15, and 1.10, 0.39 3.08, for CDH with and without cardiovascular anomalies, respectively). After adjusting for POS score, lower PcCO2 levels (OR=1.25 per 5mmHg decrease, P=0.003) were associated with better survival. CONCLUSIONS: Neonates with CDH have a high prevalence of congenital malformations. However, after adjusting for POS score the presence of additional anomalies was not associated with survival. The POS score and admission PcCO2 were important prognosticating factors for survival. PMID- 26259559 TI - Bloodstream infections during the onset of necrotizing enterocolitis and their relation with the pro-inflammatory response, gut wall integrity and severity of disease in NEC. AB - INTRODUCTION: Bacterial involvement is believed to play a pivotal role in the development and disease outcome of NEC. However, whether a bloodstream infection (BSI) predisposes to NEC (e.g. by activating the pro-inflammatory response) or result from the loss of gut wall integrity during NEC development is a longstanding question. OBJECTIVE: We hypothesize that the occurrence of a BSI plays a complementary role in the pathogenesis of NEC. The first aim of the study was to correlate the occurrence of a BSI during the early phase of NEC with intestinal fatty acid-binding protein (I-FABP) levels, as a marker for loss of gut wall integrity owing to mucosal damage, and Interleukin (IL)-8 levels, as a biomarker for the pro-inflammatory cascade in NEC. The second aim of the study was to investigate the relation between the occurrence of a BSI and disease outcome. MATERIAL AND METHODS: We combined data from prospective trials from two large academic pediatric surgical centers. Thirty-eight neonates with NEC, 5 neonates with bacterial sepsis, and 14 controls were included. RESULTS: BSIs occurred in 10/38 (26%) neonates at NEC onset. No association between the occurrence of BSIs and I-FABP levels in plasma (cohort 1: median 11ng/mL (range 0.8-298), cohort 2: median 6.8ng/mL (range 1.3-15)) was found in NEC patients (cohort 1: p=0.41; cohort 2: p=0.90). In addition, the occurrence of BSIs did not correlate with IL-8 (median 1562pg/mL (range 150-7,500); p=0.99). While the occurrence of a BSI was not correlated with Bell's stage (p=0.85), mortality was higher in patients with a BSI (p=0.005). CONCLUSION: The low incidence of BSIs and the absent association of both the markers for loss of gut wall integrity and the pro-inflammatory response during the early phase of NEC, support the hypothesis that the presence of a BSI does not precede NEC. PMID- 26259561 TI - And Pavlov still rings a bell: summarising the evidence for the use of a bell in Pavlov's iconic experiments on classical conditioning. PMID- 26259560 TI - Is the tide turning again for cephalosporin resistance in Neisseria gonorrhoeae in Europe? Results from the 2013 European surveillance. AB - BACKGROUND: The emerging resistance to the extended-spectrum cephalosporins (ESCs) in Neisseria gonorrhoeae together with increasing incidence of gonorrhoea cases in many countries have been global public health concerns. However, in recent years the levels of ESC resistance have decreased in several regions worldwide. We describe the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) data from 2013, and compare them to corresponding data from 2009-2012. METHODS: During 2013, N. gonorrhoeae isolates from 21 participating countries were examined. Antimicrobial susceptibility testing (Etest or agar dilution) was performed for cefixime, ceftriaxone, ciprofloxacin, azithromycin, spectinomycin and gentamicin. Statistical analyses were performed to identify significant changes in resistance between years and to investigate associations between patients with resistant gonococcal isolates and collected epidemiological variables. RESULTS: In total, 93 (4.7 %) of 1994 isolates displayed resistance to cefixime, representing an increase compared to the 3.9 % detected in 2012 (p = 0.23). Cefixime resistance was detected in 13 (61.9 %) of the 21 countries. Cefixime resistance among men who have sex with men was only 1.2 %, compared to 5.6 % and 6.1 % in females and male heterosexuals, respectively. The univariate analysis confirmed that isolates resistant to cefixime were more likely to be from females (OR 4.87, p < 0.01) or male heterosexuals (OR 5.32, p < 0.01). Seven (0.4 %) isolates displayed ceftriaxone resistance (in addition to cefixime resistance) compared to three and 10 isolates in 2012 and 2011, respectively. All 93 isolates with cefixime resistance were additionally resistant to ciprofloxacin and 16 (17.2 %) were also resistant to azithromycin. Among all tested isolates (n = 1994), the ciprofloxacin resistance level (52.9 %) was higher than in 2012 (50.1 %; p = 0.08), and azithromycin resistance (5.4 %) increased since 2012 (4.5 %; p = 0.16). CONCLUSIONS: In 2013, the ESC resistance was again slightly increasing in Europe. This emphasises the importance of implementing the actions outlined in the European and additional response plans, particularly activities strengthening the surveillance of antimicrobial resistance. Ceftriaxone combined with azithromycin remains a satisfactory option for the first-line treatment of gonorrhoea. However novel antimicrobials (new derivatives of previously developed antimicrobials or newly developed antimicrobials) for effective monotherapy or at least inclusion in new dual antimicrobial therapy regimens (combined with previously developed antimicrobials or novel antimicrobials) will likely be required. PMID- 26259562 TI - Late-life memory trajectories in relation to incident dementia and regional brain atrophy. AB - The trajectory, or slope, of cognitive decline may provide differentiation of older adults with and without incipient neurodegenerative disease. Cognitive aging phenotypes based on memory trajectories could be used as outcome measures for clinical trials or observational studies of risk and protective factors for dementia. This study used growth mixture modeling (GMM) to identify trajectory groups based on age- and education-corrected composite memory scores derived from immediate, delayed and recognition trials of the Selective Reminding Test. Participants included 2593 participants initially without dementia (mean age at entry = 76) in a community-based study of aging and dementia in northern Manhattan. Trajectory groups were compared on consensus diagnoses of dementia and structural MRI measures of hippocampal volume and entorhinal cortical thickness. Heterogeneity in memory trajectories allowed us to identify four groups: Stable High (43.5 %), Stable-Low (17.1 %), Decliner (26.8 %), and Rapid Decliner (12.5 %). Decliners had more brain atrophy and higher rates of conversion to dementia. This study highlights the heterogeneity in cognitive aging and provides evidence that most elderly maintain memory function as they age. Associations with dementia and imaging measures validate subgroups of older adults identified with GMM based on their memory trajectories. Future research should use these memory trajectory phenotypes to determine whether dementia risk and protective factors differ for individuals following different memory trajectories. PMID- 26259563 TI - Color vision impairment in multiple sclerosis points to retinal ganglion cell damage. AB - Multiple Sclerosis (MS) results in color vision impairment regardless of optic neuritis (ON). The exact location of injury remains undefined. The objective of this study is to identify the region leading to dyschromatopsia in MS patients' NON-eyes. We evaluated Spearman correlations between color vision and measures of different regions in the afferent visual pathway in 106 MS patients. Regions with significant correlations were included in logistic regression models to assess their independent role in dyschromatopsia. We evaluated color vision with Hardy Rand-Rittler plates and retinal damage using Optical Coherence Tomography. We ran SIENAX to measure Normalized Brain Parenchymal Volume (NBPV), FIRST for thalamus volume and Freesurfer for visual cortex areas. We found moderate, significant correlations between color vision and macular retinal nerve fiber layer (rho = 0.289, p = 0.003), ganglion cell complex (GCC = GCIP) (rho = 0.353, p < 0.001), thalamus (rho = 0.361, p < 0.001), and lesion volume within the optic radiations (rho = -0.230, p = 0.030). Only GCC thickness remained significant (p = 0.023) in the logistic regression model. In the final model including lesion load and NBPV as markers of diffuse neuroaxonal damage, GCC remained associated with dyschromatopsia [OR = 0.88 95 % CI (0.80-0.97) p = 0.016]. This association remained significant when we also added sex, age, and disease duration as covariates in the regression model. Dyschromatopsia in NON-eyes is due to damage of retinal ganglion cells (RGC) in MS. Color vision can serve as a marker of RGC damage in MS. PMID- 26259565 TI - Broadband excitation pulses with variable RF amplitude-dependent flip angle (RADFA). AB - Pulse sequences in NMR spectroscopy sometimes require the adjustment of effective flip angles with respect to experiment-specific or sample-specific parameters. Here, we present a quality factor for efficient optimization of offset compensated broadband excitation pulses with RF amplitude-dependent effective flip angles (RADFA). After proof of principle, physical limits of RF amplitude restricted and RF power-restricted broadband RADFA pulses are explored and corresponding pulse shapes and performances characterized in detail. PMID- 26259564 TI - Essential oil of Artemisia vestita exhibits potent in vitro and in vivo antibacterial activity: Investigation of the effect of oil on biofilm formation, leakage of potassium ions and survival curve measurement. AB - The aim of the present study was to investigate the chemical composition of the essential oil of Artemisia vestita and to determine the antibacterial activity of the essential oil and its two major components, grandisol and 1,8-cineole, against certain respiratory infection-causing bacterial strains, in vitro and in vivo. The chemical composition of the essential oil was analyzed using gas chromatography-mass spectrometry. A micro-well dilution method was used to determine the minimum inhibition concentration (MIC) values of the essential oil and its major constituents. A model of Streptococcus pyogenes infection in mice was used to determine its in vivo activities. Lung and blood samples were obtained to assess bacterial cell counts. Toxicity evaluation of the essential oil and its components was completed by performing biochemical analysis of the serum, particularly monitoring aspartate transaminase, alanine transaminase, urea and creatinine. The essential oil exhibited potent antibacterial activity, whereas the two major constituents were less potent. The essential oil exhibited MIC values between 20 and 80 ug/ml, while the values of the two constituents were between 130 and 200 ug/ml. Scanning electron microscopy results demonstrated that the essential oil inhibited biofilm formation and altered its architecture. Survival curves indicated that the essential oil led to a reduction in the viability of different bacteria. The essential oil also induced significant leakage of potassium ions from S. pyogenes. The essential oil (100 ug/mouse) and grandisol (135 ug/mouse) significantly reduced the number of viable bacterial cells in the lungs (P<0.01). However, intake of 100 ug/mouse of essential oil or grandisol 135 ug/mouse once or twice each day for 9 days did not produce any toxic effects in the mice. In conclusion, the in vitro and in vivo results suggested that the essential oil of A. vestita and one of its major constituents, grandisol, can significantly inhibit the growth of different bacterial strains. PMID- 26259566 TI - A transferable plasticity region in Campylobacter coli allows isolates of an otherwise non-glycolytic food-borne pathogen to catabolize glucose. AB - Thermophilic Campylobacter species colonize the intestine of agricultural and domestic animals commensally but cause severe gastroenteritis in humans. In contrast to other enteropathogenic bacteria, Campylobacter has been considered to be non-glycolytic, a metabolic property originally used for their taxonomic classification. Contrary to this dogma, we demonstrate that several Campylobacter coli strains are able to utilize glucose as a growth substrate. Isotopologue profiling experiments with (13) C-labeled glucose suggested that these strains catabolize glucose via the pentose phosphate and Entner-Doudoroff (ED) pathways and use glucose efficiently for de novo synthesis of amino acids and cell surface carbohydrates. Whole genome sequencing of glycolytic C. coli isolates identified a genomic island located within a ribosomal RNA gene cluster that encodes for all ED pathway enzymes and a glucose permease. We could show in vitro that a non glycolytic C. coli strain could acquire glycolytic activity through natural transformation with chromosomal DNA of C. coli and C. jejuni subsp. doylei strains possessing the ED pathway encoding plasticity region. These results reveal for the first time the ability of a Campylobacter species to catabolize glucose and provide new insights into how genetic macrodiversity through intra- and interspecies gene transfer expand the metabolic capacity of this food-borne pathogen. PMID- 26259567 TI - Stochastic simulation of Boolean rxncon models: towards quantitative analysis of large signaling networks. AB - BACKGROUND: Cellular decision-making is governed by molecular networks that are highly complex. An integrative understanding of these networks on a genome wide level is essential to understand cellular health and disease. In most cases however, such an understanding is beyond human comprehension and requires computational modeling. Mathematical modeling of biological networks at the level of biochemical details has hitherto relied on state transition models. These are typically based on enumeration of all relevant model states, and hence become very complex unless severely--and often arbitrarily--reduced. Furthermore, the parameters required for genome wide networks will remain underdetermined for the conceivable future. Alternatively, networks can be simulated by Boolean models, although these typically sacrifice molecular detail as well as distinction between different levels or modes of activity. However, the modeling community still lacks methods that can simulate genome scale networks on the level of biochemical reaction detail in a quantitative or semi quantitative manner. RESULTS: Here, we present a probabilistic bipartite Boolean modeling method that addresses these issues. The method is based on the reaction-contingency formalism, and enables fast simulation of large networks. We demonstrate its scalability by applying it to the yeast mitogen-activated protein kinase (MAPK) network consisting of 140 proteins and 608 nodes. CONCLUSION: The probabilistic Boolean model can be generated and parameterized automatically from a rxncon network description, using only two global parameters, and its qualitative behavior is robust against order of magnitude variation in these parameters. Our method can hence be used to simulate the outcome of large signal transduction network reconstruction, with little or no overhead in model creation or parameterization. PMID- 26259568 TI - First outline and baseline data of a randomized, controlled multicenter trial to evaluate the health economic impact of home telemonitoring in chronic heart failure - CardioBBEAT. AB - BACKGROUND: Evidence that home telemonitoring for patients with chronic heart failure (CHF) offers clinical benefit over usual care is controversial as is evidence of a health economic advantage. METHODS: Between January 2010 and June 2013, patients with a confirmed diagnosis of CHF were enrolled and randomly assigned to 2 study groups comprising usual care with and without an interactive bi-directional remote monitoring system (Motiva(r)). The primary endpoint in CardioBBEAT is the Incremental Cost-Effectiveness Ratio (ICER) established by the groups' difference in total cost and in the combined clinical endpoint "days alive and not in hospital nor inpatient care per potential days in study" within the follow-up of 12 months. RESULTS: A total of 621 predominantly male patients were enrolled, whereof 302 patients were assigned to the intervention group and 319 to the control group. Ischemic cardiomyopathy was the leading cause of heart failure. Despite randomization, subjects of the control group were more often in NYHA functional class III-IV, and exhibited peripheral edema and renal dysfunction more often. Additionally, the control and intervention groups differed in heart rhythm disorders. No differences existed regarding risk factor profile, comorbidities, echocardiographic parameters, especially left ventricular and diastolic diameter and ejection fraction, as well as functional test results, medication and quality of life. While the observed baseline differences may well be a play of chance, they are of clinical relevance. Therefore, the statistical analysis plan was extended to include adjusted analyses with respect to the baseline imbalances. CONCLUSIONS: CardioBBEAT provides prospective outcome data on both, clinical and health economic impact of home telemonitoring in CHF. The study differs by the use of a high evidence level randomized controlled trial (RCT) design along with actual cost data obtained from health insurance companies. Its results are conducive to informed political and economic decision making with regard to home telemonitoring solutions as an option for health care. Overall, it contributes to developing advanced health economic evaluation instruments to be deployed within the specific context of the German Health Care System. TRIAL REGISTRATION: ClinicalTrials.gov NCT02293252 ; date of registration: 10 November 2014. PMID- 26259569 TI - Implementation of clinical guidelines on diabetes and hypertension in urban Mongolia: a qualitative study of primary care providers' perspectives and experiences. AB - BACKGROUND: Hypertension and diabetes, key risk factors for cardiovascular disease, are significant health problems globally. As cardiovascular disease is one of the leading causes of mortality in Mongolia since 2000, clinical guidelines on arterial hypertension and diabetes were developed and implemented in 2011. This paper explores the barriers and enablers influencing the implementation of these guidelines in the primary care setting. METHODS: A phenomenological qualitative study with semi-structured interviews was conducted to explore the implementation of the diabetes and hypertension guidelines at the primary care level, as well as to gain insight into how practitioners view the usability and practicality of the guidelines. Ten family health centres were randomly chosen from a list of all the family health centres (n = 136) located in Ulaanbaatar City. In each centre, a focus group discussion with nurses (n = 20) and individual interviews with practice doctors (n = 10) and practice managers (n = 10) were conducted. Data was analysed using a thematic approach utilising the Theoretical Domains Framework. RESULTS: The majority of the study participants reported being aware of the guidelines and that they had incorporated them into their daily practice. They also reported having attended guideline training sessions which were focused on practice skill development. The majority of participants expressed satisfaction with the wide range of resources that had been supplied to them by the Mongolian Government to assist with the implementation of the guidelines. The resources, supplied from 2011 onwards, included screening devices, equipment for blood tests, medications and educational materials. Other enablers were the participants' commitment and passion for guideline implementation and their belief in the simplicity and practicality of the guidelines. Primary care providers reported a number of challenges in implementing the guidelines, including frustration caused by increased workload and long waiting times, time constraints, difficulties with conflicting tasks and low patient health literacy. CONCLUSIONS: This study provides evidence that comprehensive and rigorous dissemination and implementation strategies increase the likelihood of successful implementation of new guidelines in low resource primary care settings. It also offers some key lessons that might be carefully considered when other evidence-based clinical guidelines are to be put into effect in low resource settings and elsewhere. PMID- 26259570 TI - Integrated analysis of miRNA, gene, and pathway regulatory networks in hepatic cancer stem cells. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. HCC has a poor prognosis associated with tumor recurrence and drug resistance, which has been attributed to the existence of hepatic cancer stem cells (HCSCs). However, the characteristics and regulatory mechanisms of HCSCs remain unclear. We therefore established a novel system to enrich HCSCs and we demonstrate that these HCSCs exhibit cancer stem cell properties. METHODS: We used miRNA and mRNA high-throughput sequencing data sets to determine molecular signatures and regulatory mechanisms in HCSCs. Paired miRNA and gene deep sequencing data in HCSCs versus HCC cells were used to identify candidate biomarkers of HCSCs. Using network analysis, we studied the relationship between miRNA and gene biomarkers, and KEGG pathway enrichment analysis was performed to study the function of candidate biomarkers. RESULTS: We identified 9 up- and 9 down-regulated miRNAs and 115 up- and 402 down-regulated genes in HCSCs compared with HCC cells. A miRNA-gene network was constructed using 651 miRNA-gene interactions (between 7 up-regulated miRNAs and 274 down-regulated genes), and 103 miRNA-gene interactions (between 9 down-regulated miRNAs and 62 up-regulated genes). Pathway enrichment analysis identified five tumor invasion- and metastasis-related pathways and MAPK signaling associated with HCSCs. We further discovered two novel pathways that likely play a role in the regulation of HCSCs. CONCLUSIONS: We identified a molecular expression signature and pathway regulatory mechanisms in HCSCs with potential diagnostic and therapeutic value. PMID- 26259571 TI - Developing treatment for adrenocortical carcinoma. AB - Cancer of the adrenal cortex (ACC) is a rare endocrine malignancy with limited treatment options. Patients typically present with autonomous hormonal overproduction and/or a large abdominal mass. Hormonal assays and medical imaging can be diagnostic, but urinary steroid profiling might be a more sensitive technique to assess malignancy in adrenal tumours. The stage of the disease at diagnosis is the most important prognostic factor. The current staging system needs refinement, especially to separate aggressive from indolent disease in stage IV patients and to select patients who need adjuvant treatment after complete surgical resection. Regarding the latter, assessing the proliferation index Ki-67 seems the best tool currently available. Genomic profiling is expected to become of clinical relevance in the future. Medical therapy is centred on the adrenolytic drug mitotane, which carries considerable toxicity and is not easy to manage. Its tolerability and long plasma level build-up phase may be improved by therapeutic drug monitoring based on pharmacokinetic modelling and intensive counselling of patients. Current chemotherapy regimens can offer disease stabilization in about 50% of patients, but an objective response should be expected in <25%. Research on targeted therapy and immunotherapy is difficult in this rare disease with often heavily pre-treated patients and has not yet been successful. Quality of care should be ensured by treating patients in centres with established experience in multidisciplinary oncologic care, who adhere to prevailing guidelines and state-of-the-art in diagnostic and treatment concepts. International collaboration in fundamental research and clinical trials is the key to further elucidate the pathogenesis and to improve patient care. PMID- 26259573 TI - Correction. PMID- 26259572 TI - Primary giant cell carcinomas of the lung: a clinicopathological and immunohistochemical analysis of seven cases. AB - AIMS: Seven cases of primary giant cell carcinomas of the lung are presented. METHODS AND RESULTS: The patients were five women and two men between the ages of 48 and 72 years (average: 63 years). Clinically, the patients presented with symptoms of cough, chest pain, dyspnoea and general malaise. Diagnostic imaging revealed the presence of intrapulmonary masses; five tumours were located in the right lung and two in the left, with a general predilection for the upper lobes. All patients underwent surgical resection and staging of their tumours. Five patients were staged as T2 and T3 with nodal metastasis, while two patients in stages T1 and T3, respectively, had no nodal disease. Histologically, the giant cells were typed as syncytiotrophoblast-like or 'null type', according to the expression of beta-human chorionic gonadotrophin or expression of cytokeratin alone. Follow-up information revealed that five patients died within a period of 1-3 years, while two patients remain alive between 1 and 3 years. CONCLUSIONS: The cases presented herein highlight the importance of separating these tumours from the group of sarcomatoid carcinomas and analysing them carefully by immumohistochemical means, as we believe that these neoplasms represent a specific tumour entity. PMID- 26259574 TI - Biomek Cell Workstation: A Variable System for Automated Cell Cultivation. AB - Automated cell cultivation is an important tool for simplifying routine laboratory work. Automated methods are independent of skill levels and daily constitution of laboratory staff in combination with a constant quality and performance of the methods. The Biomek Cell Workstation was configured as a flexible and compatible system. The modified Biomek Cell Workstation enables the cultivation of adherent and suspension cells. Until now, no commercially available systems enabled the automated handling of both types of cells in one system. In particular, the automated cultivation of suspension cells in this form has not been published. The cell counts and viabilities were nonsignificantly decreased for cells cultivated in AutoFlasks in automated handling. The proliferation of manual and automated bioscreening by the WST-1 assay showed a nonsignificant lower proliferation of automatically disseminated cells associated with a mostly lower standard error. The disseminated suspension cell lines showed different pronounced proliferations in descending order, starting with Jurkat cells followed by SEM, Molt4, and RS4 cells having the lowest proliferation. In this respect, we successfully disseminated and screened suspension cells in an automated way. The automated cultivation and dissemination of a variety of suspension cells can replace the manual method. PMID- 26259575 TI - A qualitative study exploring perceived barriers to infant feeding and caregiving among adolescent girls and young women in rural Bangladesh. AB - BACKGROUND: Infant feeding and caregiving by adolescent girls and young women in rural Bangladesh remains relatively understudied despite high potential vulnerability of younger mothers and their children due to poverty and high rates of early marriage and childbearing. This key knowledge gap may hamper the effectiveness of maternal, infant and child health interventions not specifically tailored to teenage mothers. This study aimed to narrow this gap by documenting key barriers to optimal infant and young child feeding and caregiving perceived by adolescent girls and young women in rural Bangladesh. METHODS: Focus group discussions and in-depth semi-structured interviews were conducted with 70 adolescent girls and young women participating in a community-based adolescent empowerment program in two rural regions of northwestern Bangladesh. Participants were stratified into three groups: unmarried, married without child, and married with child(ren). Thematic analysis was performed to elucidate dominant ideas regarding challenges with child feeding and caregiving across participant strata. RESULTS: Participants in all three strata and in both geographical regions attributed actual and anticipated caregiving difficulties to five major contextual factors: early marriage, maternal time allocation conflicts, rural life, short birth intervals, and poverty. Indications are that many girls and young women anticipate difficulties in feeding and caring for their future children from an early age, and often prior to motherhood. Participants articulated both perceived need and unmet demand for additional education in infant and young child feeding, childcare, and family planning techniques. CONCLUSIONS: Provision during adolescence of appropriate education, services and financial aid to support best practices for infant feeding and childcare could significantly improve maternal self-efficacy, mental health, nutrition security and young childcare, nutrition and health in rural Bangladesh. Lessons learned can be applied in future programs aimed at supporting adolescent women along a continuum of care. PMID- 26259576 TI - Erotomania and psychotic depression. PMID- 26259577 TI - Nidotherapy: The expansion of environmental treatment. PMID- 26259578 TI - Commentary on Autism Spectrum Disorder: Presentation and prevalence in a nationally representative Australian sample--service implications. PMID- 26259579 TI - 18F-Florbetapir Binds Specifically to Myocardial Light Chain and Transthyretin Amyloid Deposits: Autoradiography Study. AB - BACKGROUND: (18)F-florbetapir is a promising imaging biomarker for cardiac light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR). Our aim, using human autopsy myocardial specimens, was to test the hypothesis that (18)F-florbetapir binds specifically to myocardial AL and ATTR amyloid deposits. METHODS AND RESULTS: We studied myocardial sections from 30 subjects with autopsy-documented AL (n=10), ATTR (n=10), and nonamyloid controls (n=10) using (18)F-florbetapir and cold florbetapir compound and digital autoradiography. Total and nonspecific binding of (18)F-florbetapir was determined using the maximum signal intensity values. Specific binding of (18)F-florbetapir was calculated by subtracting nonspecific from total binding measurements (in decays per minute/mm(2), DPM mm(2)) and was compared with cardiac structure and function on echocardiography and the histological extent of amyloid deposits. Diffuse or focally increased (18)F-florbetapir uptake was noted in all AL and ATTR samples and in none of the control samples. Compared with control samples, mean (18)F-florbetapir-specific uptake was significantly higher in the amyloid samples (0.94+/-0.43 versus 2.00+/ 0.58 DPM/mm(2); P<0.001), and in the AL compared with the ATTR samples (2.48+/ 0.40 versus 1.52+/-0.22 DPM/mm(2); P<0.001). The samples from subjects with atypical echocardiographic features of amyloidosis showed quantitatively more intense (18)F-florbetapir-specific uptake compared with control samples (1.50+/ 0.17 versus 0.94+/-0.43 DPM/mm(2); P=0.004), despite smaller amyloid extent than in subjects with typical echocardiograms. CONCLUSIONS: (18)F-florbetapir specifically binds to myocardial AL and ATTR deposits in humans and offers the potential to screen for the 2 most common types of myocardial amyloid. PMID- 26259580 TI - Left Ventricular Myocardial Function in Children With Pulmonary Hypertension: Relation to Right Ventricular Performance and Hemodynamics. AB - BACKGROUND: Through ventricular interdependence, pulmonary hypertension (PH) induces left ventricular (LV) dysfunction. We hypothesized that LV strain/strain rate, surrogate measures of myocardial contractility, are reduced in pediatric PH and relate to invasive hemodynamics, right ventricular strain, and functional measures of PH. METHODS AND RESULTS: At 2 institutions, echocardiography was prospectively performed in 54 pediatric PH patients during cardiac catheterization, and in 54 matched controls. Patients with PH had reduced LV global longitudinal strain (LS; -18.8 [-17.3 to -20.4]% versus -20.2 [-19.0 to 20.9]%; P=0.0046) predominantly because of reduced basal (-12.9 [-10.8 to -16.3]% versus -17.9 [-14.5 to -20.7]%; P<0.0001) and mid (-17.5 [-15.5 to -19.0]% versus -21.1 [-19.1 to -23.0]%; P<0.0001) septal strain. Basal global circumferential strain was reduced (-18.7 [-15.7 to -22.1]% versus -20.6 [-19.0 to -22.5]%; P=0.0098), as were septal and free-wall segments. Mid circumferential strain was reduced within the free-wall. Strain rates were reduced in similar patterns. Basal septum LS, the combined average LS of basal and mid interventricular septal segments, correlated strongly with degree of PH (r=0.66; P<0.0001), pulmonary vascular resistance (r=0.60; P<0.0001), and right ventricular free-wall LS (r=0.64; P<0.0001). Brain natriuretic peptide levels correlated moderately with septal LS (r=0.48; P=0.0038). PH functional class correlated moderately with LV free-wall LS (r=-0.48; P=0.0051). The septum, shared between ventricles and affected by septal shift, was the most affected LV region in PH. CONCLUSIONS: Pediatric PH patients demonstrate reduced LV strain/strain rate, predominantly within the septum, with relationships to invasive hemodynamics, right ventricular strain, and functional PH measures. PMID- 26259581 TI - Iron-Sensitive Cardiac Magnetic Resonance Imaging for Prediction of Ventricular Arrhythmia Risk in Patients With Chronic Myocardial Infarction: Early Evidence. AB - BACKGROUND: Recent canines studies have shown that iron deposition within chronic myocardial infarction (CMI) influences the electric behavior of the heart. To date, the link between the iron deposition and malignant ventricular arrhythmias in humans with CMI is unknown. METHODS AND RESULTS: Patients with CMI (n=94) who underwent late-gadolinium-enhanced cardiac magnetic resonance imaging before implantable cardioverter-defibrillator implantation for primary and secondary preventions were retrospectively analyzed. The predictive values of hypointense cores (HIC) in balanced steady-state free precession images and conventional cardiac magnetic resonance imaging and ECG malignant ventricular arrhythmia parameters for the prediction of primary combined outcome (appropriate implantable cardioverter-defibrillator therapy, survived cardiac arrest, or sudden cardiac death) were studied. The use of HIC within CMI on balanced steady state free precession as a marker of iron deposition was validated in a canine MI model (n=18). Nineteen patients met the study criteria with events occurring at a median of 249 (interquartile range of 540) days after implantable cardioverter defibrillator placement. Of the 19 patients meeting the primary end point, 18 were classified as HIC+, whereas only 1 was HIC-. Among the cohort in whom the primary end point was not met, there were 28 HIC+ and 47 HIC- patients. Receiver operating characteristic curve analysis demonstrated an additive predictive value of HIC for malignant ventricular arrhythmias with an increased area under the curve of 0.87 when added to left ventricular ejection fraction (left ventricular ejection fraction alone, 0.68). Both cardiac magnetic resonance imaging and histological validation studies performed in canines demonstrated that HIC regions in balanced steady-state free precession images within CMI likely result from iron depositions. CONCLUSIONS: Hypointense cores within CMI on balanced steady-state free precession cardiac magnetic resonance imaging can be used as a marker of iron deposition and yields incremental information toward improved prediction of malignant ventricular arrhythmias. PMID- 26259582 TI - Myocardial Iron and Arrhythmia Risk: Magnetic "Shades of Gray"? PMID- 26259583 TI - Crystal Structure of Insulin-Regulated Aminopeptidase with Bound Substrate Analogue Provides Insight on Antigenic Epitope Precursor Recognition and Processing. AB - Aminopeptidases that generate antigenic peptides influence immunodominance and adaptive cytotoxic immune responses. The mechanisms that allow these enzymes to efficiently process a vast number of different long peptide substrates are poorly understood. In this work, we report the structure of insulin-regulated aminopeptidase, an enzyme that prepares antigenic epitopes for cross-presentation in dendritic cells, in complex with an antigenic peptide precursor analog. Insulin-regulated aminopeptidase is found in a semiclosed conformation with an extended internal cavity with limited access to the solvent. The N-terminal moiety of the peptide is located at the active site, positioned optimally for catalysis, whereas the C-terminal moiety of the peptide is stabilized along the extended internal cavity lodged between domains II and IV. Hydrophobic interactions and shape complementarity enhance peptide affinity beyond the catalytic site and support a limited selectivity model for antigenic peptide selection that may underlie the generation of complex immunopeptidomes. PMID- 26259584 TI - Endothelial Cell Sensitization by Death Receptor Fractions of an Anti-Dengue Nonstructural Protein 1 Antibody Induced Plasma Leakage, Coagulopathy, and Mortality in Mice. AB - The mechanisms leading to the life-threatening dengue hemorrhagic fever (DHF) remain elusive. DHF preferentially occurs during secondary dengue infections, suggesting that aberrant immune responses are involved in its development. We previously demonstrated that the autoantibodies elicited by dengue virus (DENV) nonstructural protein 1 (NS1; anti-NS1 Igs) induce plasma leakage and mortality in mice with warfarinized anticoagulant suppression. However, the involved pathogenic Ig fractions of anti-NS1 Igs remain unclear. In this study, the autoreactive Igs in patients with DHF and in NS1-immunized rabbits crossreacted with TNF-related apoptosis-inducing ligand receptor 1 (death receptor [DR]4). Challenges with the DENV in a subcytotoxic dose sensitized endothelial cells to apoptosis. Treatments with the autoantibodies induced proapoptotic activities and suppressed the surface expression of endothelial anticoagulant thrombomodulin. Combined treatments comprising the DENV and DR4 affinity-purified fractions of anti-NS1 IgGs (anti-NS1-DR4 Ig), but not preimmune control IgGs, in subcytotoxic doses led to apoptosis in endothelial cells. Treatments with the anti-NS1-DR4 Ig led to plasma leakage, coagulopathy, and morality in mice with warfarinized anticoagulant suppression. These results suggest that DR4-induced endothelial cell sensitization through NS1-elicited autoantibodies exacerbates anticoagulant suppression, vascular injury, and plasma leakage. Detecting and blocking anti-DR Igs in patients may be novel strategies for managing severe DENV infection. PMID- 26259585 TI - IL-17A Contributes to the Pathogenesis of Endometriosis by Triggering Proinflammatory Cytokines and Angiogenic Growth Factors. AB - Endometriosis is a chronic, inflammatory disease characterized by the growth of endometrial tissue in aberrant locations outside the uterus. Neoangiogenesis or establishment of new blood supply is one of the fundamental requirements of endometriotic lesion survival in the peritoneal cavity. IL-17A is emerging as a potent angiogenic and proinflammatory cytokine involved in the pathophysiology of several chronic inflammatory diseases such as rheumatoid arthritis and psoriasis. However, sparse information is available in the context of endometriosis. In this study, we demonstrate the potential importance of IL-17A in the pathogenesis and pathophysiology of endometriosis. The data show a differential expression of IL 17A in human ectopic endometriotic lesions and matched eutopic endometrium from women with endometriosis. Importantly, surgical removal of lesions resulted in significantly reduced plasma IL-17A concentrations. Immunohistochemistry revealed localization of IL-17A primarily in the stroma of matched ectopic and eutopic tissue samples. In vitro stimulation of endometrial epithelial carcinoma cells, Ishikawa cells, and HUVECs with IL-17A revealed significant increase in angiogenic (vascular endothelial growth factor and IL-8), proinflammatory (IL-6 and IL-1beta), and chemotactic cytokines (G-CSF, CXCL12, CXCL1, and CX3CL1). Furthermore, IL-17A promoted tubulogenesis of HUVECs plated on Matrigel in a dose dependent manner. Thus, we provide the first evidence, to our knowledge, that endometriotic lesions produce IL-17A and that the removal of the lesion via laparoscopic surgery leads to the significant reduction in the systemic levels of IL-17A. Taken together, our data show a likely important role of IL-17A in promoting angiogenesis and proinflammatory environment in the peritoneal cavity for the establishment and maintenance of endometriosis lesions. PMID- 26259586 TI - MyD88 Signaling Regulates Steady-State Migration of Intestinal CD103+ Dendritic Cells Independently of TNF-alpha and the Gut Microbiota. AB - Intestinal homeostasis and induction of systemic tolerance to fed Ags (i.e., oral tolerance) rely on the steady-state migration of small intestinal lamina propria dendritic cells (DCs) into draining mesenteric lymph nodes (MLN). The majority of these migratory DCs express the alpha integrin chain CD103, and in this study we demonstrate that the steady-state mobilization of CD103(+) DCs into the MLN is in part governed by the IL-1R family/TLR signaling adaptor molecule MyD88. Similar to mice with complete MyD88 deficiency, specific deletion of MyD88 in DCs resulted in a 50-60% reduction in short-term accumulation of both CD103(+)CD11b(+) and CD103(+)CD11b(-) DCs in the MLN. DC migration was independent of caspase-1, which is responsible for the inflammasome-dependent proteolytic activation of IL-1 cytokine family members, and was not affected by treatment with broad-spectrum antibiotics. Consistent with the latter finding, the proportion and phenotypic composition of DCs were similar in mesenteric lymph from germ-free and conventionally housed mice. Although TNF-alpha was required for CD103(+) DC migration to the MLN after oral administration of the TLR7 agonist R848, it was not required for the steady-state migration of these cells. Similarly, TLR signaling through the adaptor molecule Toll/IL-1R domain containing adapter inducing IFN-beta and downstream production of type I IFN were not required for steady-state CD103(+) DC migration. Taken together, our results demonstrate that MyD88 signaling in DCs, independently of the microbiota and TNF alpha, is required for optimal steady-state migration of small intestinal lamina propria CD103(+) DCs into the MLN. PMID- 26259588 TI - Shiga toxin-producing escherichia coli infections in Norway, 1992-2012: characterization of isolates and identification of risk factors for haemolytic uremic syndrome. AB - BACKGROUND: Shiga toxin-producing E. coli (STEC) infection is associated with haemolytic uremic syndrome (HUS). Therefore Norway has implemented strict guidelines for prevention and control of STEC infection. However, only a subgroup of STEC leads to HUS. Thus, identification of determinants differentiating high risk STEC (HUS STEC) from low risk STEC (non-HUS STEC) is needed to enable implementation of graded infectious disease response. METHODS: A national study of 333 STEC infections in Norway, including one STEC from each patient or outbreak over two decades (1992-2012), was conducted. Serotype, virulence profile, and genotype of each STEC were determined by phenotypic or PCR based methods. The association between microbiological properties and demographic and clinical data was assessed by univariable analyses and multiple logistic regression models. RESULTS: From 1992 through 2012, an increased number of STEC cases including more domestically acquired infections were notified in Norway. O157 was the most frequent serogroup (33.6 %), although a decrease of this serogroup was seen over the last decade. All 25 HUS patients yielded STEC with stx2, eae, and ehxA. In a multiple logistic regression model, age <=5 years (OR = 16.7) and stx2a (OR = 30.1) were independently related to increased risk of HUS. eae and hospitalization could not be modelled since all HUS patients showed these traits. The combination of low age (<=5 years) and the presence of stx2a, and eae gave a positive predictive value (PPV) for HUS of 67.5 % and a negative predictive value (NPV) of 99.0 %. SF O157:[H7] and O145:H?, although associated with HUS in the univariable analyses, were not independent risk factors. stx1 (OR = 0.1) was the sole factor independently associated with a reduced risk of HUS (NPV: 79.7 %); stx2c was not so. CONCLUSIONS: Our results indicate that virulence gene profile and patients' age are the major determinants of HUS development. PMID- 26259589 TI - Engaging scientists: An online survey exploring the experience of innovative biotechnological approaches to controlling vector-borne diseases. AB - BACKGROUND: Pioneering technologies (e.g., nanotechnology, synthetic biology or climate engineering) are often associated with potential new risks and uncertainties that can become sources of controversy. The communication of information during their development and open exchanges between stakeholders is generally considered a key issue in their acceptance. While the attitudes of the public to novel technologies have been widely considered there has been relatively little investigation of the perceptions and awareness of scientists working on human or animal diseases transmitted by arthropods. METHODS: Consequently, we conducted a global survey on 1889 scientists working on aspects of vector-borne diseases, exploring, under the light of a variety of demographic and professional factors, their knowledge and awareness of an emerging biotechnology that has the potential to revolutionize the control of pest insect populations. RESULTS: Despite extensive media coverage of key developments (including releases of manipulated mosquitoes into human communities) this has in only one instance resulted in scientist awareness exceeding 50% on a national or regional scale. We document that awareness of pioneering releases significantly relied on private communication sources that were not equally accessible to scientists from countries with endemic vector-borne diseases (dengue and malaria). In addition, we provide quantitative analysis of the perceptions and knowledge of specific biotechnological approaches to controlling vector-borne disease, which are likely to impact the way in which scientists around the world engage in the debate about their value. CONCLUSIONS: Our results indicate that there is scope to strengthen already effective methods of communication, in addition to a strong demand by scientists (expressed by 79.9% of respondents) to develop new, creative modes of public engagement. PMID- 26259590 TI - AT2R autoantibodies block angiotensin II and AT1R autoantibody-induced vasoconstriction. AB - Activating autoantibodies to the angiotensin type 1 receptor (AT1R) are associated with hypertensive disorders. The angiotensin type 2 receptor (AT2R) is known to counter-regulate the actions of AT1R. We investigated whether AT2R autoantibodies produced in immunized rabbits will activate AT2R and suppress the vasopressor responses to angiotensin II and AT1R-activating autoantibodies. Five rabbits immunized with a peptide corresponding to the second extracellular loop of AT2R developed high AT2R antibody titers. Rabbit anti-AT2R sera failed to directly dilate isolated rat cremaster arterioles; however, when co-perfused with angiotensin II or AT1R-activating autoantibodies, the anti-AT2R sera significantly inhibited their contractile effects. Rabbit anti-AT2R sera recognized a predominant sequence near the N-terminus of the AT2R second extracellular loop. A decoy peptide based on this sequence effectively reversed the opposing effect of the anti-AT2R sera on angiotensin II-induced contraction of rat cremaster arterioles. A similar blockade of the anti-AT2R sera effect was observed with the AT2R antagonist PD 123319 and the guanylyl cyclase inhibitor 1H [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. Rabbit anti-AT2R sera reacted specifically with AT2R. No cross-reactivity with AT1R was observed. Blood pressure did not change in immunized animals. However, the pressor responses to incremental angiotensin II infusions were blunted in immunized animals. Thirteen subjects with primary aldosteronism demonstrated increased AT2R autoantibody levels compared with normal controls. In conclusion, AT2R autoantibodies produced in immunized rabbits have the ability to activate AT2R and counteract the AT1R mediated vasoconstriction. These autoantibodies provide useful and selective tools for the study of their roles in blood pressure regulation and possible therapeutic intervention. PMID- 26259591 TI - Let-7i: lethal weapon against angiotensin ii-induced cardiac injury. PMID- 26259592 TI - Decreased arterial elasticity in children with nondialysis chronic kidney disease is related to blood pressure and not to glomerular filtration rate. AB - We compared large artery mechanical properties in children with nondialysis stages of chronic kidney disease with those in children with normal renal function, examining the potential effect of blood pressure (BP) components and level of renal dysfunction. Common carotid artery mechanical properties, carotid femoral pulse wave velocity, and carotid and peripheral BP were measured in children (n=226) with nondialysis chronic kidney disease (n=188; 11.9+/-3.7 years; 26%, 25%, 30%, 16%, and 3% in stages 1, 2, 3, 4 and 5, respectively) and healthy controls (n=38; 11.5+/-3.3 years). In children with nondialysis chronic kidney disease when compared with healthy controls, at similar levels of peripheral and carotid BP, carotid artery diastolic diameter and wall thickness were similar. In those with suboptimal BP (>=75th percentile), indices of arterial elasticity indicated greater stiffness than in healthy normotensive controls (distensibility: 92+/-31 versus 114+/-33 kPa(-1)*10(-3), P=0.03; compliance: 2.1+/-0.7 versus 2.6+/-0.7 m(2) kPa(-1)*10(-6), P=0.02; Young elastic modulus: 0.151+/-0.068 versus 0.109+/-0.049 kPa*10(3), P=0.02; and wall stress: 83.6+/-23.5 versus 68.7+/-14.9 kPa, P=0.02). In all children, mechanical properties were independently related to carotid and peripheral BP components but not to estimated glomerular filtration rate. In children with nondialysis chronic kidney disease, changes in elastic properties of the carotid artery are primarily related to BP and not to glomerular renal function. PMID- 26259593 TI - Regulation of sympathetic nerve activity during the cold pressor test in normotensive pregnant and nonpregnant women. AB - Baseline neurovascular transduction is reduced in normotensive pregnancy; however, little is known about changes to neurovascular transduction during periods of heightened sympathetic activation. We tested the hypothesis that, despite an exacerbated muscle sympathetic nerve activity (microneurography) response to cold pressor stimulation, the blunting of neurovascular transduction in normotensive pregnant women would result in similar changes in vascular resistance and mean arterial pressure (Finometer) relative to nonpregnant controls. Baseline neurovascular transduction was reduced in pregnant women relative to controls when expressed as the quotient of both total resistance and mean arterial pressure and sympathetic burst frequency (0.32+/-0.07 versus 0.58+/ 0.16 mm Hg/L/min/bursts/min, P<0.001 and 2.4+/-0.7 versus 3.6+/-0.8 mm Hg/bursts/min, P=0.001). Sympathetic activation was greater across all 3 minutes of cold pressor stimulation in the pregnant women relative to the nonpregnant controls. Peak sympathoexcitation was also greater in pregnant than in nonpregnant women, whether expressed as sympathetic burst frequency (+17+/-13 versus +7+/-8 bursts/min, P=0.049), burst incidence (+17+/-9 versus +6+/-11 bursts/100 hb, P=0.03), or total activity (+950+/-660 versus +363+/-414 arbitrary units, P=0.04). However, neurovascular transduction during peak cold pressor induced sympathoexcitation remained blunted in pregnant women (0.25+/-0.11 versus 0.45+/-0.08 mm Hg/L/min/bursts/min, P<0.001 and 1.9+/-1.0 versus 3.2+/-0.9 mm Hg/bursts/min, P=0.006). Therefore, mean arterial pressure (93+/-21 versus 99+/-6 mm Hg, P=0.4) and total peripheral resistance (12+/-3 versus 14+/-3 mm Hg/L/min) were not different between pregnant and nonpregnant women during peak sympathoexcitation. These data indicate that the third trimester of normotensive pregnancy is associated with reductions in neurovascular transduction, which result in the dissociation of sympathetic outflow from hemodynamic outcomes, even during cold pressor-induced sympathoexcitation. PMID- 26259594 TI - Pathological effects of obstructive apneas during the sleep cycle in an animal model of cerebral small vessel disease. AB - We tested the hypothesis that apneas during the sleep cycle exacerbate hypertension and accelerate changes that occur with cerebral small vessel disease. Obstructive sleep apnea was modeled by intermittent inflations of a chronically implanted tracheal balloon to occlude the airway during the sleep cycle (termed OSA) in spontaneously hypertensive stroke-prone (SHRSP) rats, a model of cerebral small vessel disease. SHRSP rats and their parent strain, Wistar Kyoto (WKY) rats, were exposed to OSA for 2 weeks (from 9 to 11 or from 18 to 20 weeks). At 9 weeks, hypertension was developing in the SHRSP rats and was firmly established by 18 weeks. OSA exposure increased systolic blood pressure in SHRSP rats by ~30 mm Hg in both age groups compared with shams that were surgically prepared but not exposed to OSA (P<0.05). OSA exposure also increased systolic blood pressure in WKY rats by 20 and 37 mm Hg at 11 and 20 weeks, respectively (P<0.05). OSA exposure in SHRSP rats compromised blood-brain barrier integrity in white matter at both 11 and 20 weeks of age when compared with SHRSP sham rats (P<0.05). Microglia were activated in SHRSP rats exposed to OSA but not in sham rats at 11 weeks (P<0.05). At 20 weeks, microglia were activated in sham SHRSP rats (P<0.05) compared with WKY sham rats and were not further activated by OSA. Neither was blood-brain barrier integrity altered nor microglia activated in any of the WKY groups. We conclude that OSA accelerates the onset of the cerebral pathologies associated with cerebral small vessel disease in SHRSP, but not WKY, rats. PMID- 26259595 TI - MicroRNA Let-7i negatively regulates cardiac inflammation and fibrosis. AB - Angiotensin II stimulates fibroblast proliferation and substantially alters gene expression patterns leading to cardiac remodeling, but the mechanisms for such differences are unknown. MicroRNAs are a novel mechanism for gene expression regulation. Herein, we tested the miRNA and mRNA expression patterns in mouse heart using microarray assay and investigated their role in angiotensin II induced cardiac remodeling. We found that let-7i was dynamically downregulated in angiotensin II-infused heart at day 3 and 7 and had the most targets that were mainly associated with cardiac inflammation and fibrosis. Overexpression or knockdown of let-7i in cultured cardiac fibroblasts demonstrated that let-7i played an inhibitory effect on the expression of its targets interleukin-6 and collagens. Furthermore, delivery of let-7i to mouse significantly inhibited angiotensin II-induced cardiac inflammation and fibrosis in a dose-dependent manner. Conversely, knockdown of let-7i aggravated this effect. Together, our results clearly demonstrate that let-7i acts as a novel negative regulator of angiotensin II-induced cardiac inflammation and fibrosis by suppressing the expression of interleukin-6 and multiple collagens in the heart and may represent a new potential therapeutic target for treating hypertensive cardiac fibrosis. PMID- 26259596 TI - Agreement between 24-hour salt ingestion and sodium excretion in a controlled environment. AB - Accurately collected 24-hour urine collections are presumed to be valid for estimating salt intake in individuals. We performed 2 independent ultralong-term salt balance studies lasting 105 (4 men) and 205 (6 men) days in 10 men simulating a flight to Mars. We controlled dietary intake of all constituents for months at salt intakes of 12, 9, and 6 g/d and collected all urine. The subjects' daily menus consisted of 27 279 individual servings, of which 83.0% were completely consumed, 16.5% completely rejected, and 0.5% incompletely consumed. Urinary recovery of dietary salt was 92% of recorded intake, indicating long-term steady-state sodium balance in both studies. Even at fixed salt intake, 24-hour urine collection for sodium excretion (UNaV) showed infradian rhythmicity. We defined a +/-25 mmol deviation from the average difference between recorded sodium intake and UNaV as the prediction interval to accurately classify a 3-g difference in salt intake. Because of the biological variability in UNaV, only every other daily urine sample correctly classified a 3-g difference in salt intake (49%). By increasing the observations to 3 consecutive 24-hour collections and sodium intakes, classification accuracy improved to 75%. Collecting seven 24 hour urines and sodium intake samples improved classification accuracy to 92%. We conclude that single 24-hour urine collections at intakes ranging from 6 to 12 g salt per day were not suitable to detect a 3-g difference in individual salt intake. Repeated measurements of 24-hour UNaV improve precision. This knowledge could be relevant to patient care and the conduct of intervention trials. PMID- 26259597 TI - Influence of hypoxia and irradiation on osteopontin expression in head and neck cancer and glioblastoma cell lines. AB - BACKGROUND: Tumor hypoxia is a known risk factor for reduced response to radiotherapy. The evaluation of noninvasive methods for the detection of hypoxia is therefore of interest. Osteopontin (OPN) has been discussed as an endogenous hypoxia biomarker. It is overexpressed in many cancers and is involved in tumor progression and metastasis. METHODS: To examine the influence of hypoxia and irradiation on osteopontin expression we used different cell lines (head and neck cancer (Cal27 and FaDu) and glioblastoma multiforme (U251 and U87)). Cells were treated with hypoxia for 24 h and were then irradiated with doses of 2 and 8 Gy. Osteopontin expression was analyzed on mRNA level by quantitative real-time RT PCR (qPCR) and on protein level by western blot. Cell culture supernatants were evaluated for secreted OPN by ELISA. RESULTS: Hypoxia caused an increase in osteopontin protein expression in all cell lines. In Cal27 a corresponding increase in OPN mRNA expression was observed. In contrast the other cell lines showed a reduced mRNA expression under hypoxic conditions. After irradiation OPN mRNA expression raised slightly in FaDu and U87 cells while it was reduced in U251 and stable in Cal27 cells under normoxia. The combined treatment (hypoxia and irradiation) led to a slight increase of OPN mRNA after 2 Gy in U251 (24 h) and in U87 (24 and 48 h) cell lines falling back to base line after 8 Gy. This effect was not seen in Cal27 or in FaDu cells. Secreted OPN was detected only in the two glioblastoma cell lines with reduced protein levels under hypoxic conditions. Again the combined treatment resulted in a minor increase in OPN secretion 48 hours after irradiation with 8 Gy. CONCLUSION: Osteopontin expression is strongly modulated by hypoxia and only to a minor extent by irradiation. Intracellular OPN homeostasis seems to vary considerably between cell lines. This may explain the partly conflicting results concerning response prediction and prognosis in the clinical setting. PMID- 26259599 TI - Completeness and Reliability of the Republic of South Africa National Tuberculosis (TB) Surveillance System. AB - BACKGROUND: Accurate surveillance data are paramount to effective TB control. The Republic of South Africa's National TB Control Program (NTP) has conducted TB surveillance since 1995 and adopted the Electronic TB Register (ETR) in 2005. This evaluation aimed to determine the completeness and reliability of data in the Republic of South Africa's TB Surveillance System. METHODS: Three of nine provinces, three subdistricts per province, and 54 health facilities were selected by stratified random sampling. At each facility, 30 (or all if <30) patients diagnosed in Quarter 1 2009 were randomly selected for review. Patient information was evaluated across two paper and four electronic sources. Completeness of program indicators between paper and electronic sources was compared with chi-square tests. The kappa statistic was used to evaluate agreement of values. RESULTS: Over one-third (33.7 %) of all persons with presumptive TB recorded as smear positive in the TB Suspect Register did not have any records documenting notification, treatment, or management for TB disease. Of 1339 persons with a record as a TB patient at the facility, 1077 (80 %) were recorded in all data sources. Over 98 % of records contained complete age and sex data. Completeness varied for HIV status (53-86 %; p < 0.001) and DOT during the intensive phase of treatment (17-54 %; p < 0.001). Agreement for sex was excellent across sources (kappa 0.94); moderate for patient type (0.78), treatment regimen (0.79), treatment outcome (0.71); and poor for HIV status (0.33). CONCLUSIONS: The current evaluation revealed that one-third of persons diagnosed with TB disease may not have been notified of their disease or initiated on treatment ('initial defaulters'). The ETR is not capturing all TB patients. Further, among patients with a TB record, completeness and reliability of information in the TB Surveillance System is inconsistent across data sources. Actions are urgently needed to ensure that all diagnosed patients are treated and managed and improve the integrity of surveillance information. PMID- 26259598 TI - eNOS polymorphisms as predictors of efficacy of bevacizumab-based chemotherapy in metastatic colorectal cancer: data from a randomized clinical trial. AB - BACKGROUND: Bevacizumab plus chemotherapy is a widely used therapeutic option for first-line treatment of metastatic colorectal cancer (mCRC). However, molecular predictors of bevacizumab efficacy have not yet been identified. We analyzed vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) polymorphisms in relation to response to bevacizumab. METHODS: Two hundred and thirty-seven patients with mCRC enrolled onto the phase III prospective multicentre randomized "Italian Trial in Advanced Colorectal Cancer (ITACa)" trial were evaluated. One hundred fourteen patients received chemotherapy plus bevacizumab (CT + B) and 123 received chemotherapy (CT) alone. Five single nucleotide polymorphisms (SNPs) (-2578, -1498, -1154, -634 and +936) for VEGF and 2 SNPs (-786, +894) and one variable number tandem repeat in intron 4 for eNOS were analyzed for each patient. The polymorphisms were assessed in relation to progression-free survival (PFS), objective response rate (ORR) and overall survival (OS). RESULTS: VEGF 936C/T, eNOS +894 G/T and VNTR were significantly correlated with outcome in CT + B patients, but not in CT-only patients. In particular, patients with a specific haplotype combination of the 2 eNOS polymorphisms (defined eNOS Haplo1/Haplo1 and eNOS Haplo 2/Haplo2) showed significantly longer PFS (15.0 vs 9.1 months, P = 0.001) and OS (34.5 vs 20.5 months P = 0.002), and a higher ORR (71 vs 45.9%, P = 0.013) than those with the other genotypes, respectively. CONCLUSIONS: Specific eNOS polymorphisms may be capable of identifying a subset of mCRC patients who are more responsive to bevacizumab-based chemotherapy. If confirmed, these results would permit individually tailored treatment with bevacizumab. PMID- 26259600 TI - The intracellular domain of cell adhesion molecule 1 is present in emphysematous lungs and induces lung epithelial cell apoptosis. AB - BACKGROUND: Pulmonary emphysema is characterized histologically by destruction of alveolar walls and enlargement of air spaces due to lung epithelial cell apoptosis. Cell adhesion molecule 1 (CADM1) is an immunoglobulin superfamily member expressed in lung epithelial cells. CADM1 generates a membrane-associated C-terminal fragment, alphaCTF, through A disintegrin- and metalloprotease-10 mediated ectodomain shedding, subsequently releasing the intracellular domain (ICD) through gamma-secretase-mediated intramembrane shedding of alphaCTF. alphaCTF localizes to mitochondria and induces apoptosis in lung epithelial cells. alphaCTF contributes to the development and progression of emphysema as a consequence of increased CADM1 ectodomain shedding. The purpose of this study was to examine whether the ICD makes a similar contribution. RESULTS: The ICD was synthesized as a 51-amino acid peptide, and its mutant was synthesized by substituting seven amino acids and deleting two amino acids. These peptides were labeled with fluorescein isothiocyanate and were introduced into various cell lines. ICD peptide-derived fluorescence was well visualized in lung epithelial cells at the site of Mitotracker mitochondrial labeling, but was detected in locations other than mitochondria in other cell types. Mutant peptide-derived fluorescence was detected in locations other than mitochondria, even in lung epithelial cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays revealed that transduction of the ICD peptide increased the proportion of apoptotic cells 2- to 5-fold in the lung epithelial cell lines, whereas the mutant peptide did not. Abundance of the ICD was below the Western blot detection limit in emphysematous (n = 4) and control (n = 4) human lungs. However, the ICD was detected only in emphysematous lungs when it was immunoprecipitated with anti-CADM1 antibody (4/4 vs. 0/4, P = 0.029). CONCLUSIONS: As the abundance of ICD molecules was sparse but present, increased CADM1 shedding appeared to contribute to the development of emphysema by generating alphaCTF and the ICD in lung epithelial cells. PMID- 26259602 TI - 'Multiple-test' approach to the laboratory diagnosis of tuberculosis -perception of medical doctors from Ujjain, India. AB - BACKGROUND: Delay in diagnosis is one of the most important factors for the control of tuberculosis (TB) in endemic countries like India. As laboratory diagnosis is the mainstay for identification of active disease, we aim to explore and understand the opinions of medical doctors about the laboratory diagnosis of TB in Ujjain, India. METHODS: Sixteen qualified specialist medical doctors from Ujjain were purposefully selected for the study. Individual interviews with the doctors (13 men and 3 women), were conducted. As one interview could not be completed, data from 15 interviews were analyzed using manifest and latent content analysis. RESULTS: Based on perception of the doctors, the theme; 'challenges and need for the laboratory diagnosis of TB' emerged from the following subthemes: (i) Relationship between basic element of the TB diseases process such as 'Symptoms prior to diagnoses' and 'Clinical characteristics of TB', which were not specific enough to diagnose TB (ii) The prevailing conditions such as lack of explicit diagnostic tools, lead to the doctors using the 'multiple tests' or 'empiric treatment' approach (iii) The doctors proposed that there is a need for access to a rapid, single and simple diagnostic test, and a need for awareness and knowledge of the practitioners regarding specific TB investigations, and early referral to improve the situation at resource-limited settings. CONCLUSION: The medical specialists use a 'multiple test' or 'empiric treatment' approach to diagnose TB. According to the participants, there is a low dependence and uptake of the available laboratory TB investigations by medical practitioners. There is an urgent need to have a specific, simple and reliable test, and a protocol, to improve diagnosis of TB and to prevent development of resistant TB. PMID- 26259604 TI - Aniline Is Rapidly Converted Into Paracetamol Impairing Male Reproductive Development. AB - Industrial use of aniline is increasing worldwide with production estimated to surpass 5.6 million metric tons in 2016. Exposure to aniline occurs via air, diet, and water augmenting the risk of exposing a large number of individuals. Early observations suggest that aniline is metabolized to paracetamol/acetaminophen, likely explaining the omnipresence of low concentrations of paracetamol in European populations. This is of concern as recent studies implicate paracetamol as a disrupter of reproduction. Here, we show through steroidogenic profiling that exposure to aniline led to increased levels of the Delta4 steroids, suggesting that the activity of CYP21 was decreased. By contrast, paracetamol decreased levels of androgens likely through inhibition of CYP17A1 activity. We confirm that aniline in vivo is rapidly converted to paracetamol by the liver. Intrauterine exposure to aniline and paracetamol in environmental and pharmaceutical relevant doses resulted in shortening of the anogenital distance in mice, a sensitive marker of fetal androgen levels that in humans is associated with reproductive malformations and later life reproductive disorders. In conclusion, our results provide evidence for a scenario where aniline, through its conversion into antiandrogenic paracetamol, impairs male reproductive development. PMID- 26259605 TI - Aryl Hydrocarbon Receptor Activation Synergistically Induces Lipopolysaccharide Mediated Expression of Proinflammatory Chemokine (c-c motif) Ligand 20. AB - The Ah receptor (AHR) is directly involved in the regulation of both innate and adaptive immunity. However, these activities are poorly understood at the level of gene regulation. The chemokine (c-c motif) ligand 20 (CCL20) plays a nonredundant role in the chemoattraction of C-C motif receptor 6 expressing cells (eg, T cells and others). A survey of promoter regions of chemokine genes revealed that there are several putative dioxin responsive elements in the mouse Ccl20 promoter. The addition of an AHR agonist along with lipopolysaccharide (LPS) to cultured primary peritoneal macrophages results in synergistic induction of both Ccl20 mRNA and protein, compared with each compound alone. Through the use of macrophage cultures derived from Ahr(-) (/) (-) and Ahr(nls/nls) mice, it was established that expression of the AHR and its ability to translocate into the nucleus are necessary for AHR ligand-mediated synergistic induction of Ccl20. Gel shift analysis determined that a potent tandem AHR binding site ~3.1 kb upstream from the transcriptional start site can efficiently bind the AHR/ARNT (aryl hydrocarbon receptor/AHR nuclear translocator) heterodimer upon activation with a number of AHR agonists. Furthermore, studies reveal that LPS increases AHR levels on the Ccl20 promoter while decreasing HDAC1 occupancy. The level of Ccl20 constitutive expression in the colon is greatly attenuated in Ahr(-) (/) (-) mice. These studies suggest that the presence of AHR ligands during localized inflammation may augment chemokine expression, thus participating in the overall response to pathogens. PMID- 26259606 TI - Analysis of Glycogen Synthase Kinase Inhibitors That Regulate Cytochrome P450 Expression in Primary Human Hepatocytes by Activation of beta-Catenin, Aryl Hydrocarbon Receptor and Pregnane X Receptor Signaling. AB - Cytochrome P450 (CYP) expression and activity are not homogeneous in the liver lobules. Indeed, CYPs are mainly expressed and induced in centrilobular hepatocytes. The wingless-type MMTV integration site family (WNT)/beta-catenin pathway was identified as a major regulator of this zonal organization. We have recently demonstrated that in primary human hepatocytes (PHHs), the expression of CYP2E1, CYP1A2, and aryl hydrocarbon receptor (AhR), but not of CYP3A4, is regulated by the WNT/beta-catenin pathway in response to WNT3a, its canonical activator. Here, we investigated whether glycogen synthase kinase 3beta (GSK3beta) inhibitors, which mimic the action of WNT molecules, could be used in PHHs to activate the beta-catenin pathway to study CYP expression. We assessed the activity of 6BIO (6-bromoindirubin-3'-oxime), CHIR99021 (6-((2-((4-(2,4 dichlorophenyl)-5-(4methyl-1H-imidazol-2-yl)pyrimidin-2-yl)amino)ethyl)amino) nicotinonitrile), and GSK3iXV (Pyridocarbazolo-cyclopentadienyl Ruthenium complex GSK3 inhibitor XV) that belong to structurally different families of GSK3beta inhibitors. Using small interfering RNAs, reporter gene assays, and molecular docking predictions, we demonstrated that GSK3beta inhibitors can activate the WNT/beta-catenin pathway in PHHs to regulate CYP2E1 expression. We also found that 6BIO and GSK3iXV are AhR full agonists that participate, through AhR signaling, to CYP1A2 induction. Conversely, CHIR99021 is an AhR partial agonist, and a pregnane X receptor ligand and partial agonist, thus regulating CYP1A2 and CYP3A4 gene expression in a beta-catenin-independent manner. In conclusion, GSK3beta inhibitors can activate the WNT/beta-catenin pathway in PHHs. Nevertheless, their role in CYP regulation should be analyzed with caution as these molecules can interact with xenosensors. PMID- 26259607 TI - Noninvasive Biomarker Candidates for Cadmium-Induced Nephrotoxicity by 2DE/MALDI TOF-MS and SILAC/LC-MS Proteomic Analyses. AB - Cadmium (Cd(2+)) is a major environmental pollutant that induces cytotoxicity by heavy-metal accumulation. Prolonged Cd(2+) exposure leads to cell damage by oxidative stress mainly in the kidneys, a critical organ for detoxification. To identify reliable on invasive protein biomarkers for Cd(2+)-induced nephrotoxicity, we performed 2-dimensional gel electrophoresis/matrix-assisted laser desorption/ionization time of flight mass spectra and stable isotope labeling by amino acids in cell culture/liquid chromatography-mass spectrometry analyses using conditioned media (CM) of HK-2 human kidney epithelial cells treated with CdCl2. Here, we identified heat shock cognate 71 kDa protein isoform1 (HSPA8) and alpha-enolase (ENO1) as potential biomarker candidates for the evaluation of Cd(2+)-induced nephrotoxicity. Treatment with CdCl2 increased the protein level of HSPA8 in CM and lysates of HK-2 cells. The mRNA level of HSPA8 was also increased by CdCl2 treatment, indicating transcriptional regulation. The level of ENO1 was increased in CM, but not in lysates of CdCl2 treated HK-2 cells. CdCl2 did not affect the mRNA level of ENO1. We provide evidence that the increases of HSPA8 and ENO1 in CM were due to Cd(2+)-induced cell death through oxidative stress. The increases of HSPA8 and ENO1 levels were also detected in CM of HK-2 cells treated with other nephrotoxic agents, such as HgCl2, NaAsO2, cisplatin, amphotericin B, and cyclosporine A. Urine and kidney tissues of CdCl2-treated rats showed increased levels of HSPA8. Taken together, this study identified HSPA8 and ENO1 as noninvasive biomarker candidates by 2 comparative proteomic analyses. These new biomarker candidates may have potential as alternatives to traditional biomarkers for the efficient and sensitive assessment of nephrotoxicity. PMID- 26259608 TI - Bridging Functional and Structural Cardiotoxicity Assays Using Human Embryonic Stem Cell-Derived Cardiomyocytes for a More Comprehensive Risk Assessment. AB - More relevant and reliable preclinical cardiotoxicity tests are required to improve drug safety and reduce the cost of drug development. Current in vitro testing strategies predominantly take the form of functional assays to predict the potential for drug-induced ECG abnormalities in vivo. Cardiotoxicity can also be structural in nature, so a full and efficient assessment of cardiac liabilities for new chemical entities should account for both these phenomena. As well as providing a more appropriate nonclinical model for in vitro cardiotoxicity testing, human stem cell-derived cardiomyocytes offer an integrated system to study drug impact on cardiomyocyte structure as well as function. Employing human embryonic stem cell-derived cardiacmyocytes (hESC-CMs) on 3 assay platforms with complementary insights into cardiac biology (multielectrode array assay, electrophysiology; impedance assay, cell movement/beating; and high content analysis assay, subcellular structure) we profiled a panel of 13 drugs with well characterized cardiac liabilities (Amiodarone, Aspirin, Astemizole, Axitinib, AZT, Bepridil, Doxorubicin, E-4031, Mexiletine, Rosiglitazone, Sunitinib, Sibutramine, and Verapamil). Our data show good correlations with previous studies and reported clinical observations. Using multiparameter phenotypic profiling techniques we demonstrate the dynamic relationship that exists between functional and structural toxicity, and the benefits of this more holistic approach to risk assessment. We conclude by showing for the first time how the advent of transparent MEA plate technology enables functional and structural cardiotoxic responses to be recorded from the same cell population. This approach more directly links changes in morphology of the hESC-CMs with recorded electrophysiology signatures, offering even greater insight into the wide range of potential drug impacts on cardiac physiology, with a throughput that is more amenable to early drug discovery. PMID- 26259609 TI - Etoposide Induces Necrosis Through p53-Mediated Antiapoptosis in Human Kidney Proximal Tubule Cells. AB - The p53 protein is an important transcription factor that modulates signaling pathways for both cell death and survival. Its antiapoptotic mechanisms that correlate with necrotic and apoptotic cell death are not well understood. Here, we report that etoposide promotes progression of the DNA damage response as well as necrotic morphological changes including plasma membrane rupture using carbon nanotube-tipped/atomic force microscopy (CNT/AFM) probes in human kidney proximal tubule (HK-2) cells. Inhibition of p53 abrogated cell cycle arrest and led to a decrease in the expression levels of repair proteins that were induced by DNA damage. Mitochondrial biogenesis and cytosolic production of reactive oxygen species were also reduced after p53 inhibition; the latter change induced mitochondrial superoxide accumulation and mitochondrial damage, which triggered the activation of caspase 3. Inhibition of p53 also led to a loss of cell adhesion and converted necrotic cell death to apoptotic cell death, with appreciable cell shrinkage and appearance of apoptotic bodies that were observed using CNT/AFM probes. Thus, our study demonstrated that p53 protects against apoptosis, and leads to etoposide-induced necrosis. These results are expected to aid in the understanding of mechanism of antiapoptosis and its relationship to cell death. PMID- 26259610 TI - Rapamycin and its analogues (rapalogs) for Tuberous Sclerosis Complex-associated tumors: a systematic review on non-randomized studies using meta-analysis. AB - BACKGROUND: Rapamycin has gained significant attention for its potential activity in reducing the size of TSC-associated tumors, thus providing alternative to surgery. This study aimed at determining the efficacy of rapamycin and rapalogs for reducing the size of TSC-associated solid tumors in patients with Tuberous Sclerosis Complex (TSC). METHODS: Our data sources included electronic searches of the PubMed. We included into our meta-analysis any type of non-randomized study that reported the use of rapamycin and rapalogs for reducing the size of TSC-associated solid tumors in patients with TSC. Data was entered into Cochrane Review Manager Version 5.3 and analyzed. RESULTS: Four case reports and 4 clinical trials were included. Five patients from the case reports (all with SEGA) and 91 patients from the clinical trials (41 with SEGA, 63 with kidney angiomyolipoma and 5 with liver angiomyolipoma) were included into the analysis. Volume and diameter of SEGAs were significantly reduced by mean difference of 1.23 cc (95 % CI -2.32 to -0.13; p = 0.03) and 7.91 mm (95 % CI -11.82 to -4.01; p < 0.0001), respectively. Volume and mean of sum of longest diameter of kidney angiomyolipomas were significantly reduced by mean difference of 39.5 cc (95 % CI -48.85 to -30.15; p <0.00001) and 69.03 mm (95 % CI -158.05 to 12.65; p = 0.008), respectively. In liver angiomyolipomas, however, reduction in tumor size was not evident. Sum of longest diameter of liver angiomyolipomas in 4 patients were enlarged by 2.7 mm (95 % CI 28.42 to -23.02) by the end of treatment, though not significant (p = 0.84). CONCLUSIONS: Rapamycin and rapalogs showed efficacy towards reducing the size of SEGA and kidney angiomyolipoma but not liver angiomyolipomas. This finding is strengthening the conclusion of our Cochrane systematic review on the randomized trials. PMID- 26259612 TI - Using prediction markets of market scoring rule to forecast infectious diseases: a case study in Taiwan. AB - BACKGROUND: The Taiwan CDC relied on the historical average number of disease cases or rate (AVG) to depict the trend of epidemic diseases in Taiwan. By comparing the historical average data with prediction markets, we show that the latter have a better prediction capability than the former. Given the volatility of the infectious diseases in Taiwan, historical average is unlikely to be an effective prediction mechanism. METHODS: We designed and built the Epidemic Prediction Markets (EPM) system based upon the trading mechanism of market scoring rule. By using this system, we aggregated dispersed information from various medical professionals to predict influenza, enterovirus, and dengue fever in Taiwan. RESULTS: EPM was more accurate in 701 out of 1,085 prediction events than the traditional baseline of historical average and the winning ratio of EPM versus AVG was 64.6 % for the target week. For the absolute prediction error of five diseases indicators of three infectious diseases, EPM was more accurate for the target week than AVG except for dengue fever confirmed cases. The winning ratios of EPM versus AVG for the confirmed cases of severe complicated influenza case, the rate of enterovirus infection, and the rate of influenza-like illness in the target week were 69.6 %, 83.9 and 76.0 %, respectively; instead, for the prediction of the confirmed cases of dengue fever and the confirmed cases of severe complicated enterovirus infection, the winning ratios of EPM were all below 50 %. CONCLUSIONS: Except confirmed cases of dengue fever, EPM provided accurate, continuous and real-time predictions of four indicators of three infectious diseases for the target week in Taiwan and outperformed the historical average data of infectious diseases. PMID- 26259611 TI - CD300f immunoreceptor contributes to peripheral nerve regeneration by the modulation of macrophage inflammatory phenotype. AB - BACKGROUND: It has recently become evident that activating/inhibitory cell surface immune receptors play a critical role in regulating immune and inflammatory processes in the central nervous system (CNS). The immunoreceptor CD300f expressed on monocytes, neutrophils, and mast cells modulates inflammation, phagocytosis, and outcome in models of autoimmune demyelination, allergy, and systemic lupus erythematosus. On the other hand, a finely regulated inflammatory response is essential to induce regeneration after injury to peripheral nerves since hematogenous macrophages, together with resident macrophages and de-differentiated Schwann cells, phagocyte distal axonal and myelin debris in a well-orchestrated inflammatory response. The possible roles and expression of CD300f and its ligands have not been reported under these conditions. METHODS: By using quantitative PCR (QPCR) and CD300f-IgG2a fusion protein, we show the expression of CD300f and its ligands in the normal and crush injured sciatic nerve. The putative role of CD300f in peripheral nerve regeneration was analyzed by blocking receptor-ligand interaction with the same CD300f-IgG2a soluble receptor fusion protein in sciatic nerves of Thy1-YFP-H mice injected at the time of injury. Macrophage M1/M2 polarization phenotype was also analyzed by CD206 and iNOS expression. RESULTS: We found an upregulation of CD300f mRNA and protein expression after injury. Moreover, the ligands are present in restricted membrane patches of Schwann cells, which remain stable after the lesion. The lesioned sciatic nerves of Thy1-YFP-H mice injected with a single dose of CD300f-IgG2a show long lasting effects on nerve regeneration characterized by a lower number of YFP-positive fibres growing into the tibial nerve after 10 days post lesion (dpl) and a delayed functional recovery when compared to PBS- or IgG2a-administered control groups. Animals treated with CD300f-IgG2a show at 10 dpl higher numbers of macrophages and CD206-positive cells and lower levels of iNOS expression than both control groups. At later time points (28 dpl), increased numbers of macrophages and iNOS expression occur. CONCLUSIONS: Taken together, these results show that the pair CD300f ligand is implicated in Wallerian degeneration and nerve regeneration by modulating both the influx and phenotype of macrophages. PMID- 26259613 TI - Traumatic intracranial hypotension due to a Tarlov cyst tear. PMID- 26259614 TI - A research update on the potential roles of aquaporin 4 in neuroinflammation. AB - The presence of aquaporins (AQPs) in the brain has led to intense research on the underlying roles of this family of proteins under both normal and pathological conditions. Aquaporin 4 (AQP4) is the major water-channel membrane protein expressed in the central nervous system (CNS), primarily in astrocytes. Emerging evidence suggests that AQP4 could play an important role in water and ion homeostasis in the brain, and it has been studied in various brain pathological conditions. However, far less is known about the potential for AQP4 to influence neuroinflammation and, furthermore, its potential role in neurodegenerative disorders such as Alzheimer's disease (AD). It has been suggested that the pathogenesis of many clinical diseases, such as neuromyelitis optica (NMO), multiple sclerosis (MS) and brain injuries, is related to the regulation of AQP4 expression. Investigating the effects of AQP4 on microglia and astrocytes could be important to understand its role in the pathogenesis of neuroinflammation. Although the exact roles of non-steroidal anti-inflammatory drugs (NSAIDs) in protection against the detrimental effects of neuroinflammation remain unclear, research into the possible neuroprotective effects of AQP4 against neuroinflammation regulation seems to be important for future investigations. PMID- 26259615 TI - Hydrogenative Kinetic Resolution of Vinyl Sulfoxides. AB - Enantiopure sulfoxides are valuable precursors of organosulfur compounds with broad application in organic and pharmaceutical chemistry. An unprecedented strategy for obtaining highly enantioenriched sulfoxides based on a hydrogenative kinetic resolution using Rh-complexes of phosphine-phosphite ligands as catalysts is reported. After optimization, highly efficient conditions for the kinetic resolution of racemic sulfoxides have been identified. This methodology has been applied to a set of racemic aralkyl or aryl vinyl sulfoxides and allowed the isolation of both recovered and reduced products in excellent yields and enantioselectivities (up to 99% and 97% ee, respectively; 16 examples). PMID- 26259616 TI - Parasitological, serological and molecular survey of Trypanosoma evansi infection in dromedary camels from Cholistan Desert, Pakistan. AB - BACKGROUND: Surra, a vector borne disease caused by Trypanosoma (T.) evansi, affects the health, productivity and working capacity of camels. Since clinical signs are not pathognomonic, diagnosis must be confirmed by laboratory methods. This is a first study on the prevalence of surra in Cholistan Desert, Pakistan using a broad variety of diagnostic tests thereby emphasizing it as a risk for the dromedaries of Pakistan. METHODS: In a cross sectional study, 1005 dromedary camels from three districts in the Cholistan Desert were sampled to assess the prevalence of trypanosomosis due to T. evansi by means of parasitological (Giemsa stained thin smear), serological (formol gel test, CATT/T. evansi, ELISA/VSG RoTat 1.2, immune trypanolysis) and molecular tests (TBR1/2 PCR and RoTat 1.2 PCR). Kappa was calculated to assess the degree of agreement between different tests whereas chi-square test along with odds ratios and their 95% confidence intervals were used to study influence of breed, gender, age and locality on disease prevalence. RESULTS: Overall prevalence was 0.7% with Giemsa stained thin smears (GST), 40.1% with formol gel test (FGT), 47.7% with CATT/T. evansi, 44.2% with ELISA/VSG RoTat 1.2, 39.9 % with immune trypanolysis (TL), 31.9 % with TBR1/2 PCR and 30.5% with RoTat1.2 PCR. Based on these results, the Cholistan Desert appears to be a high risk area for surra. According to TL and TBR1/2 PCR, camels at Bahawalpur are approximately two times more likely to be infected than those in Bahawalnagar (OR = 1.8; 95% CI: 1.38-2.42) and Rahim Yar Khan (OR = 1.9; 95% CI: 1.30-2.75). Test agreement of TL was moderate with CATT/T. evansi (k = 0.43; 95% CI: 0.378-0.489) and ELISA/VSG RoTat 1.2 (k = 0.54; 95% CI: 0.489 0.594) and poor with the other tests. Test agreement between TBR1/2 PCR and RoTat1.2 PCR was almost perfect (k = 0.96; 95% CI: 0.950-0.984). We didn't find evidence for the presence of T. evansi type B in the studied population. CONCLUSION: Our study supports using antibody detection tests, rather than parasitological and molecular examination, to assess surra prevalence in camels. It also calls for implementation of measures to control surra in the Cholistan Desert. PMID- 26259618 TI - Evaluating the use of key performance indicators to evidence the patient experience. AB - AIMS AND OBJECTIVES: To test eight person-centred key performance indicators and the feasibility of an appropriate measurement framework as an approach to evidencing the patient experience. BACKGROUND: The value of measuring the quality of patient care is undisputed in the international literature, however, the type of measures that can be used to generate data that is meaningful for practice continues to be debated. This paper offers a different perspective to the 'measurement' of the nursing and midwifery contribution to the patient experience. DESIGN: Fourth generation evaluation was the methodological approach used to evaluate the implementation of the key performance indicators and measurement framework across three participating organisations involving nine practice settings. METHODS: Data were collected by repeated use of claims, concerns and issues with staff working across nine participating sites (n = 18) and the senior executives from the three partner organisations (n = 12). Data were collected during the facilitated sessions with stakeholders and analysed in conjunction with the data generated from the measurement framework. RESULTS: The data reveal the inherent value placed on the evidence generated from the implementation of the key performance indicators as reflected in the following themes: measuring what matters; evidencing the patient experience; engaging staff; a focus for improving practice; and articulating and demonstrating the positive contribution of nursing and midwifery. CONCLUSIONS: The implementation of the key performance indicators and the measurement framework has been effective in generating evidence that demonstrates the patient experience. The nature of the data generated not only privileges the patient voice but also offers feedback to nurses and midwives that can inform the development of person centred cultures. RELEVANCE TO CLINICAL PRACTICE: The use of these indicators will produce evidence of patient experience that can be used by nurse and midwives to celebrate and further inform person-centred practice. PMID- 26259617 TI - Efficacy and safety results from a Phase 3, randomized, placebo-controlled trial of subcutaneous golimumab in Chinese patients with active rheumatoid arthritis despite methotrexate therapy. AB - AIM: The efficacy and safety of golimumab + methotrexate (MTX) were evaluated in Chinese patients with active rheumatoid arthritis (RA) despite MTX therapy. METHODS: Chinese patients (n = 264) were randomly assigned (1 : 1) to receive subcutaneous injections of placebo + MTX with crossover to golimumab 50 mg + MTX at week 24 (Group 1) or to golimumab 50 mg + MTX (Group 2) every 4 weeks. Group 1 patients with inadequate response entered blinded early escape to golimumab 50 mg + MTX at week 16. At least a 20% improvement in the American College of Rheumatology (ACR20) criteria at week 14 was the primary endpoint. Other assessments included the 28-joint count Disease Activity Score using C-reactive protein (DAS28-CRP) and Health Assessment Questionnaire-Disability Index (HAQ-DI) through week 52. Adverse events (AEs) were monitored through week 56. RESULTS: ACR20 response at week 14 was significantly higher in Group 2 (40.9% [54/132]) compared with Group 1 (15.9% [21/132]; P < 0.001). Greater proportions of patients in Group 2 compared with Group 1 had a DAS28-CRP response at week 14 (65.2% vs. 30.3%, P < 0.001) or ACR20 response at week 24 (42.4% vs. 15.9%, P < 0.001), and Group 2 had a significantly greater change in HAQ-DI at week 24 ( 0.26 vs. 0.15, P < 0.001). After week 24, the proportion of patients achieving ACR20 in Group 1 approached that in Group 2. Through week 16, 23.5% of Group 1 and 26.7% of Group 2 patients reported AEs. Among golimumab + MTX-treated patients, 50.2% and 4.2% had >= 1 AE or serious AE, respectively, through week 56. No unexpected safety signals were observed. CONCLUSION: Among MTX-experienced Chinese patients with active RA, a significantly greater proportion of patients receiving golimumab + MTX had improvements in the signs and symptoms of RA compared with MTX monotherapy. Safety findings were consistent with previous studies of golimumab in patients with RA. PMID- 26259619 TI - Analysis of Enoyl-Acyl Carrier Protein Reductase Structure and Interactions Yields an Efficient Virtual Screening Approach and Suggests a Potential Allosteric Site. AB - Enoyl-acyl carrier protein reductases have an important role in fatty acid biosynthesis and are considered essential for bacterial and protozoal survival. Here, we perform a computational assessment of enoyl-acyl carrier protein reductase structures, providing insights for inhibitor design that we incorporate into a virtual screening approach. Firstly, we analyse 80 crystal structures of 16 different enoyl-acyl carrier protein reductases for their active site characteristics and druggability, finding these sites contain a readily druggable pocket, of varying size and shape. Interestingly, a high affinity, potentially allosteric site was identified for pfFabl. Analysis of the ligand-protein interactions of four enoyl-acyl carrier protein reductases from different micro organisms (InhA, pfFabl, saFabl and ecFabl), involving 59 available crystal structures, found three commonly shared interactions; constraining these interactions in docking improved enrichment of enoyl-acyl carrier protein reductase virtual screens, by up to 60% in the top 3% of the ranked library. This docking protocol also improved pose prediction, decreasing the root-mean-square deviation to crystallographic pose by up to 75% on average. The binding site analysis and knowledge-based docking protocol presented here can potentially assist in the structure-based design of new enoyl-acyl carrier protein reductase inhibitors. PMID- 26259620 TI - Nutritional properties of dried salmon silage for broiler feeding. AB - The aim of this study was to evaluate the chemical composition, energy and amino acid profile of dried salmon silage (DSS) for broilers. The DSS was obtained by acid digestion of salmon mortalities and subsequently co-dried with wheat bran in a 70:30 ratio (70 parts silage and 30 parts wheat bran). Samples of DSS were evaluated for chemical composition, gross energy, nitrogen-corrected true metabolizable energy (TMEn ), mineral content, total and digestible amino acids for broilers, and amino acid score. The chemical composition of DSS was (mean +/- SD): moisture (12.3 +/- 0.8%), crude protein (44.0 +/- 1.1%), ether extract (5.0 +/- 2.4%), crude fiber (3.3 +/- 0.4%) and ash (9.4 +/- 0.6%). The gross energy and TMEn for broilers were 4 069 kcal/kg and 2 613 kcal/kg, respectively. The DSS mineral composition showed a high content of calcium (1.01%) and phosphorus (1.08%). The DSS had high levels of digestible methionine (0.74%), lysine (2.27%), and threonine (1.16%), and did not present limiting amino acids for broilers. Nutritional composition of DSS showed high protein content with an amino acid profile considered to be suitable as a protein source for broiler feeding. PMID- 26259621 TI - Treatment strategies for dissecting aneurysms of the posterior cerebral artery. AB - BACKGROUND: Dissecting aneurysms of the posterior cerebral artery (PCA) are rare and difficult to treat because of their deep and unfamiliar locations and unusual shapes. Although several treatment modalities have been proposed, none have generated satisfying results. Our experiences with PCA-dissecting aneurysms are reviewed and the treatment strategies discussed. METHODS: All consecutive patients with PCA-dissecting aneurysm who were treated in a tertiary referral hospital between January 1998 and March 2014 were identified by retrospective review. Their clinical characteristics, radiological findings, treatment modalities and outcomes were documented. RESULTS: Of the 21 patients with 21 PCA dissecting aneurysms, 9 had subarachnoid hemorrhage and 3 had acute infarction of the thalamus at presentation. The aneurysms involved P1 (n = 4), the P1-2 junction (n = 3), mid-P2 (n = 6), P2A (n = 3), P2P (n = 1) and the P2-3 junction (n = 4). The aneurysm shapes were as follows: fusiform (n = 12), partially thrombosed (n = 8) and blood blister-like aneurysms (n = 1). The mean size was 16.6 +/- 9.7 mm. Parent artery occlusion (PAO) without bypass (n = 15), PAO with bypass (n = 2), stent-assisted endosaccular coiling (n = 3) and stent placement only (n = 1) were performed. All three patients who underwent stent-assisted endosaccular coiling and the single patient who underwent PAO without bypass developed aneurysm recurrence. Six of the ten patients who received a PAO without a balloon test occlusion (BTO) experienced PCA territory infarction, whereas only one of the five patients who received a PAO after passing the BTO experienced an infarction. CONCLUSIONS: PAO for PCA-dissecting aneurysm was effective in preventing recurrence. In addition, BTO before PAO was helpful in identifying candidates who truly needed surgical revascularization. PMID- 26259622 TI - Molecular characterisation of plasma membrane-derived vesicles. AB - Plasma membrane-derived vesicles (PMVs) are released into circulation in response to normal and stress/pathogenic conditions. They are of tremendous significance for the prediction, diagnosis, and observation of the therapeutic success of many diseases. Knowledge of their molecular characteristics and therefore functional properties would contribute to a better understanding of the pathological mechanisms leading to various diseases in which their levels are raised. The review aims at outlining and discussing the molecular characteristics of PMVs in order to bring to the fore some aspects/characteristics of PMVs that will assist the scientific community to properly understand the role of PMVs in various physiological and pathological processes. The review covers PMVs characterisation and discusses how distinct they are from exosomes and endosomes. Also, methods of PMVs analysis, importance of proper PMV level estimation/characterisation, PMVs and their constituents as well as their therapeutic significance are discussed. The review concludes by drawing attention to the importance of further study into the functions of the characteristics discussed which will lead to understanding the general role of PMVs both in health and in disease states. PMID- 26259623 TI - Determinants of Change in Air-Bone Gap and Bone Conduction in Patients Operated on for Chronic Otitis Media. AB - BACKGROUND: Middle ear surgery aims to eliminate pathology from the middle ear, improve drainage and ventilation of the postoperative cavity, and reconstruct the tympanic membrane and ossicles. The aim of this work is to define the factors that affect ABG (air-bone gap) and bone conduction in the patients operated on due to chronic otitis media. MATERIAL AND METHODS: A prospective analysis of patients operated on due to diseases of the middle ear during 2009-2012 was carried out. The cases of patients operated on for the first time due to chronic otitis media were analyzed. The analysis encompassed patients who had undergone middle ear surgery. The patients were divided into several groups taking into account the abnormalities of the middle ear mucous and damage of the ossicular chain observed during otosurgery. RESULTS: A significant hearing improvement was observed in patients with type 2 tympanoplasty in the course of chronic cholesteatoma otitis media and in patients with simple chronic inflammatory process in whom a PORP was used in the reconstruction. Granulation tissue was an unfavorable factor of hearing improvement following tympanoplasty. A significant improvement of bone conduction was observed in the patients with dry perforation without other lesions in the middle ear. The elimination of granulation lesions was a positive factor for the future improvement of the function of the inner ear. CONCLUSIONS: The presence of granuloma-related lesions in the middle ear spaces is likely to impede hearing improvement. Damage to the ossicular chain rules out the possibility of bone conduction improvement after surgery. The prognosis on tube-related simple chronic otitis media after myringoplasty, with the preserved continuity of the ossicular chain, consists of closing the ABG and leads to significant improvement of bone conduction. PMID- 26259624 TI - Activation Effect of Fullerene C60 on the Carbon Dioxide Absorption Performance of Amine-Rich Polypropylenimine Dendrimers. AB - Invited for this month's cover are Dr. Enrico Andreoli and Prof. Andrew R. Barron from the Energy Safety Research Institute (ESRI) of Swansea University. The image shows how fullerene C60 can activate amine-rich polymers toward CO2 capture for clean energy production. The Full Paper itself is available at 10.1002/cssc.201500605. PMID- 26259625 TI - Asymmetric AB3 Miktoarm Star Polymers: Synthesis, Self-Assembly, and Study of Micelle Stability Using AF4 for Efficient Drug Delivery. AB - A simple and versatile methodology, which employs a combination of ring-opening polymerization and alkyne-azide click chemistry to synthesize amphiphilic AB3 miktoarm stars, is reported. Their aqueous self-assembly behavior was studied using dynamic light scattering, fluorescence, and asymmetrical flow field-flow fractionation (AF4). AB3 miktoarm stars form micelles which incorporate curcumin with high efficiency, and significantly reduce the viability of glioblastoma cells in spheroids. We demonstrate that AF4 is an effective technique to determine the size distribution of self-assembled structures exposed to a biological medium. The ease, with which asymmetric AB3 miktoarm polymers are constructed, provides a platform that can be widely employed to deliver a variety of lipophilic drugs. PMID- 26259626 TI - Characteristics of neonates with culture-proven bloodstream infection who have low levels of C-reactive protein (?10 mg/L). AB - BACKGROUND: Elevated C-reactive protein (CRP) level is widely used in clinical practice as a marker to distinguish between neonates with or without sepsis. However, some neonates with bacteremia have a CRP level within the normal range and they are not well characterized. METHODS: All episodes of neonatal culture proven bloodstream infections (BSIs) between July 2004 and June 2012 were enrolled. Patients characteristics were compared for three CRP groups (low, <= 10 mg/L; intermediate, 11-100 mg/L; and high, > 100 mg/L) using the Chi-square test and one-way ANOVA. The sepsis-attributable mortality rates were compared using logistic regression analyses. RESULTS: Of 986 episodes of neonatal BSI, 247 (25.1 %) had CRP <=10 mg/L at the onset of clinical sepsis. In the low CRP group, patients had lower gestational age and birth weight, and an earlier occurrence of BSI. Patients with underlying gastrointestinal pathology, renal disorders, cholestasis, and pulmonary hypertension had a non-significant elevated CRP level at the onset of sepsis. In the blood culture of the low CRP group, coagulase negative staphylococci (CoNS) were relatively more common (55.9 %, p < 0.001) than the other two groups, although one-fourth were infected with gram-negative bacilli (19.0 %), fungi (2.8 %), or polymicrobial pathogens (3.6 %). Of the BSIs with initial low CRP, 29.1 % were treated with inadequate antibiotics, 13.0 % progressed to septic shock, and 5.3 % had infectious complications. The sepsis attributable mortality rate was lower in the low CRP group (4.9 %) than in the high CRP group (13.6 %). CONCLUSIONS: A considerable proportion of neonatal BSIs had a normal or low initial CRP level (<=10 mg/L), which was more likely to occur in low birth weight or extremely preterm infants, those with earlier onset of sepsis, and those infected with CoNS. Plasma CRP level should not be used to rule out severe culture-proven sepsis or guide the empirical choice of antibiotics. PMID- 26259627 TI - Late sodium current block for drug-induced long QT syndrome: Results from a prospective clinical trial. AB - Drug-induced long QT syndrome has resulted in many drugs being withdrawn from the market. At the same time, the current regulatory paradigm for screening new drugs causing long QT syndrome is preventing drugs from reaching the market, sometimes inappropriately. In this study, we report the results of a first-of-a-kind clinical trial studying late sodium (mexiletine and lidocaine) and calcium (diltiazem) current blocking drugs to counteract the effects of hERG potassium channel blocking drugs (dofetilide and moxifloxacin). We demonstrate that both mexiletine and lidocaine substantially reduce heart-rate corrected QT (QTc) prolongation from dofetilide by 20 ms. Furthermore, all QTc shortening occurs in the heart-rate corrected J-Tpeak (J-Tpeak c) interval, the biomarker we identified as a sign of late sodium current block. This clinical trial demonstrates that late sodium blocking drugs can substantially reduce QTc prolongation from hERG potassium channel block and assessment of J-Tpeak c may add value beyond only assessing QTc. PMID- 26259628 TI - Coronary CT angiography findings based on smoking status: Do ex-smokers and never smokers share a low probability of developing coronary atherosclerosis? AB - The relationship of coronary artery disease (CAD) in ex-smokers has not been elucidated, although smoking is considered to be one of the major risk factors of CAD. We investigate subclinical coronary atherosclerosis (SCA) in asymptomatic subjects with coronary computed tomography angiography (CCTA), according to smoking status, and determine whether ex-smokers share a low probability of developing CAD with never-smokers. We retrospectively enrolled 6930 self-referred asymptomatic adults who underwent both coronary artery calcium score (CACS) and CCTA. The prevalence and characteristics of SCA were assessed according to smoking status (never-, ex- and current smokers). After adjusting for variable risk factors, we used multivariate logistic regression for adjusted odds ratios (AOR) of high CACS (>100), SCA (any plaque), significant stenosis (>50 % in luminal stenosis) and each plaque type (non-calcified, mixed and calcified plaque) among the three groups. The prevalence of SCA was highest in the ex smokers (35.4 %) and the prevalence of significant stenosis in ex-smokers (6.9 %) was as high as in current smokers (6.4 %). However, after adjusting for variable risk factors, SCA was significantly correlated with both ex-smokers (AOR; 1.21) and current smokers (AOR; 1.25), whereas significant stenosis was correlated only with current smokers (AOR; 1.91). The association between SCA and ex-smokers is as strong as with current smokers, although significant stenosis is only correlated with current smokers; thus, not only quitting smoking but also never initiating smoking would be helpful to reduce the progression of the SCA. PMID- 26259629 TI - Integrated in-line coagulation-aerated ultrafiltration for drinking-water production: A case study from laboratory to pilot plant. AB - A pilot-scale study was made for drinking-water production from low-quality influents with in-line coagulation as pre-treatment of aerated ultrafiltration. Optimum flocculation parameters were previously determined in the laboratory, searching for large and strong flocs that could resist aeration without increasing the membrane fouling. Nevertheless, the comparison of the jar tests and the pilot-scale results showed that the former could help pre-dimensioning the flocculation facilities but could not precisely reproduce the behavior of the flocs in the membrane tank. The optimum coagulant dosage enabled the highest dissolved organic carbon (DOC) removal without affecting membrane fouling. Additionally, as opposed to the jar-test results, long retention times led to the lowest fouling rates while the velocity gradient affected neither the effluent quality nor the membrane fouling. These findings suggested that the influence of the flocculation parameters was masked by aeration inside the membrane tank but, even so, 43% and 82% DOC and UVA254 removals, respectively, were reached. Furthermore, the growth of the total membrane resistance with time was logarithmic instead of linear, confirming the suitability of the pre-treatment for low-quality influents. PMID- 26259631 TI - Three cadinane derivatives from the marine brown alga Dictyopteris divaricata. PMID- 26259632 TI - Increased gut hormones and insulin sensitivity index following a 3-d intervention with a barley kernel-based product: a randomised cross-over study in healthy middle-aged subjects. AB - Certain purified indigestible carbohydrates such as inulin have been shown to stimulate gut-derived hormones involved in glycaemic regulation and appetite regulation, and to counteract systemic inflammation through a gut microbiota mediated mechanism. Less is known about the properties of indigestible carbohydrates intrinsic to food. The aim of this study was to investigate the possibility to affect release of endogenous gut hormones and ameliorate appetite control and glycaemic control by ingestion of a whole-grain cereal food product rich in NSP and resistant starch in healthy humans. In all, twenty middle-aged subjects were provided with a barley kernel-based bread (BB) or a reference white wheat bread during 3 consecutive days, respectively, in a randomised cross-over design study. At a standardised breakfast the following day (day 4), blood was collected for the analysis of blood (b) glucose regulation, gastrointestinal hormones, markers of inflammation and markers of colonic fermentation; 3 d of intervention with BB increased gut hormones in plasma (p) the next morning at fasting (p-glucagon-like peptide-1; 56%) and postprandially (p-glucagon-like peptide-2; 13% and p-peptide YY; 18%). Breath H2 excretion and fasting serum (s) SCFA concentrations were increased (363 and 18%, respectively), and b-glucose (22%) and s-insulin responses (17%) were decreased after BB intervention. Insulin sensitivity index (ISI(composite)) was also improved (25%) after BB. In conclusion, 3 d of intervention with BB increased systemic levels of gut hormones involved in appetite regulation, metabolic control and maintenance of gut barrier function, as well as improved markers of glucose homoeostasis in middle-aged subjects, altogether relevant for the prevention of obesity and the metabolic syndrome. PMID- 26259630 TI - Next-generation antimicrobials: from chemical biology to first-in-class drugs. AB - The global emergence of multi-drug resistant bacteria invokes an urgent and imperative necessity for the identification of novel antimicrobials. The general lack of success in progressing novel chemical entities from target-based drug screens have prompted calls for radical and innovative approaches for drug discovery. Recent developments in chemical biology and target deconvolution strategies have revived interests in the utilization of whole-cell phenotypic screens and resulted in several success stories for the discovery and development novel drug candidates and target pathways. In this review, we present and discuss recent chemical biology approaches focusing on the discovery of novel targets and new lead molecules for the treatment of human bacterial and protozoan infections. PMID- 26259633 TI - An Optimal Mobile Service for Telecare Data Synchronization using a Role-based Access Control Model and Mobile Peer-to-Peer Technology. AB - The progress of information and communication technologies (ICT) has promoted the development of healthcare which has enabled the exchange of resources and services between organizations. Organizations want to integrate mobile devices into their hospital information systems (HIS) due to the convenience to employees who are then able to perform specific healthcare processes from any location. The collection and merage of healthcare data from discrete mobile devices are worth exploring possible ways for further use, especially in remote districts without public data network (PDN) to connect the HIS. In this study, we propose an optimal mobile service which automatically synchronizes the telecare file resources among discrete mobile devices. The proposed service enforces some technical methods. The role-based access control model defines the telecare file resources accessing mechanism; the symmetric data encryption method protects telecare file resources transmitted over a mobile peer-to-peer network. The multi criteria decision analysis method, ELECTRE (Elimination Et Choice Translating Reality), evaluates multiple criteria of the candidates' mobile devices to determine a ranking order. This optimizes the synchronization of telecare file resources among discrete mobile devices. A prototype system is implemented to examine the proposed mobile service. The results of the experiment show that the proposed mobile service can automatically and effectively synchronize telecare file resources among discrete mobile devices. The contribution of this experiment is to provide an optimal mobile service that enhances the security of telecare file resource synchronization and strengthens an organization's mobility. PMID- 26259634 TI - Temperature Measurement Inside Protective Headgear: Comparison With Core Temperatures and Indicators of Physiological Strain During Exercise in a Hot Environment. AB - Non-invasive temperature monitoring with a sensor inside protective headgear may be effective in detecting temperatures that are associated with heat illness. The purpose was to establish the relationship between in-hardhat temperatures (Tih) and core temperature (Tc) as measured by rectal (Tre) and esophageal (Tes) probes. Thirty males (age 24.57 +/- 4.32 yrs.) completed two trials: continuous submaximal exercise (CSE) and a series of high intensity 30-s sprints (HIE) with a one-minute rest between each. Exercise in both conditions was in a 36( degrees )C environment (40% RH) while wearing a standard hardhat with sensors mounted on the forehead that were monitored remotely. Exercise continued until voluntary termination or until Tc reached 39.5( degrees )C. Temperatures, heart rate, cardiorespiratory, and perceptual responses were monitored throughout. A physiological strain index (PSI) was calculated from Tc and HR. The final temperatures in the CSE condition were 38.77 +/- 0.41, 38.90 +/- 0.49 and 39.29 +/- 0.58( degrees )C and in the HIE condition, final temperatures were 38.76 +/- 0.37, 38.91 +/- 0.47, and 39.19 +/- 0.57 f (o)C for Tih, Tre, and Tes, respectively. The PSI in CSE was 9.62 +/- 062, 9.18 +/- 1.11, and 10.04 +/- 1.05, and in the HIE condition 9.67 +/- 068, 9.29 +/- 0.99. and 9.86 +/- 1.02 based on Tih, Tre and Tes, respectively. The general agreement between the Tih and other temperature measures along with the consistency as indicated by a low coefficient of variation (approx. 1%) in the recordings of the Tih sensors at the point of termination suggest that this device, or similar devices, may have application as a warning system for impending heat-related problems. PMID- 26259636 TI - Shell Cleavable Dendritic Polyglycerol Sulfates Show High Anti-Inflammatory Properties by Inhibiting L-Selectin Binding and Complement Activation. AB - A new class of fully synthetic shell cleavable multivalent polysulfates is prepared by introducing degradable linkers into a stable biocompatible dendritic polyglycerol scaffold and subsequent sulfation. The sulfated polymers show different degradation profiles, low anticoagulant and high anti-inflammatory properties, are able to efficiently bind to L-selectin and inhibit the complement activation at very low concentrations in vitro. PMID- 26259637 TI - Lesion Evaluation, Screening and Identification of Oral Neoplasia Study: an assessment of high-risk Australian populations. AB - OBJECTIVES: Population-based screening programmes which promote early detection are effective in reducing the burden of disease associated with chronic illness. The efficacy of screening for oral cancer and its preceding lesions appears promising in high-risk groups. The objective of this study is to report on the recruitment experiences and outcomes of the 'Lesion Evaluation, Screening and Identification of Oral Neoplasia Study' programme, a multicentre oral mucosal screening programme developed in South East Queensland, Australia. METHODS: Ten screening sites were established within public and private dental clinics, indigenous health clinics and a community pharmacy. Risk assessment was undertaken through a semi-structured interview and self-directed questionnaires. Oral mucosal examination was completed by one of 11 trained and calibrated dentists or oral health therapists, under conventional operatory parameters. RESULTS: The study ran for 24 months from April 2012 to April 2014. A total of 1498 participants consented to oral mucosal screening, with complete data available for 1252 (83.6%). Almost half (n = 561; 44.8%) were from an area of high disadvantage, and 59.9% reported annual household incomes below $40K (n = 750). Participants from backgrounds experiencing the highest level of disadvantage were more likely to have a history of tobacco use (P = 0.04). Those participants with low income had significantly higher prevalence ratios (PRs) of having suspicious oral mucosal lesions (PR: 3.13 and 5.85, respectively) than the most advantageous. Examiners reported difficulties in recruitment, which stemmed mainly from patient refusal due to time constraints, disinterest or embarrassment relating to their oral condition. Clinician outreach also proved inefficient in participant recruitment. CONCLUSIONS: Population-based screening for oral cancer in the Australian context was effective in identifying people at risk of developing oral lesions, but participant recruitment appears to be a significant barrier to implementation. Further strategies are required to improve the success of such a programme, as we advocate for screening in high-risk populations. PMID- 26259635 TI - Structural and functional changes in corneal innervation after laser in situ keratomileusis and their relationship with dry eye. AB - PURPOSE: The most likely etiology of post-LASIK dry eye is corneal nerve damage; however, no direct relationship between post-LASIK dry eye symptoms and nerve damage has been established, and limited information is available about the relationship between dry eye signs and corneal reinnervation after LASIK. Tear neuropeptides (SP and CGRP) are important in the maintenance of corneal nerve health, but the impact of LASIK has not yet been studied. This study evaluated changes in nerve morphology, tear neuropeptide, and dry eye, so as to establish the relationship between reinnervation and dry eye and to assess the role of tear neuropeptides in reinnervation post-LASIK. METHODS: Twenty non-dry eye volunteers who had undergone bilateral myopic-LASIK completed this study. Corneal nerve morphology (density, width, interconnections, and tortuosity), SP and CGRP concentration, and dry eye were monitored over time prior to, 1 day, 1 week, 1, 3, and 6 months post-LASIK. RESULTS: Dry eye symptoms and tear function, except for osmolarity (P = 0.003), remained unchanged post-LASIK. Corneal nerve morphology decreased immediately, and did not return to preoperative levels by 6 months post-LASIK (P < 0.001). Increased tear SP concentration was observed 3 months post-LASIK (P < 0.001). Associations between reinnervation as measured by increased density and lower tear SP (P = 0.03), and between increased density and decreased dry eye symptoms (P = 0.01) were found post-LASIK. CONCLUSION: An inverse relationship between reinnervation post-LASIK and dry eye symptoms was found, confirming that post-LASIK dry eye is a neuropathic disease. This study is the first to demonstrate an association between tear SP and post-LASIK reinnervation, suggesting that strategies for manipulating neuropeptide concentration to improve reinnervation may improve ocular comfort post-LASIK. PMID- 26259638 TI - A prospective study of the use of the Myosure resectoscope to manage endometrial polyps in an outpatient setting. AB - BACKGROUND: The Myosure resectoscope has been in use since 2009. Our unit is the first in Australia to describe the use of the Myosure device in the outpatient setting to resect endometrial polyps. AIM: To compare patient satisfaction and pain scores of pre- and postmenopausal women undergoing outpatient removal of endometrial polyps using the Myosure device. MATERIAL AND METHODS: Public hospital based prospective study. Patients (n=42) who opted to have resection of endometrial polyps under local anaethesia were recruited. Procedures were performed using a 6.25-mm hysteroscope with a MyoSure Lite device. Patient experiences were collected using a questionnaire immediately postprocedure. Pain level was assessed using 100-mm visual analogue score (VAS). Resection times and untoward events were recorded. RESULTS: Mean endometrial polyp size was 13 mm and the mean resection time was 39.4s. Complete resection was achieved in 95.2% of cases. The median VAS was 2.7 (range 0.7-7.5). The pain scores did not differ significantly between nulliparous or parous women who only had a caesarean section delivery and those who have delivered vaginally. However, VAS was statistically less in postmenopausal women in comparison with premenopausal women (2.5 vs 3.2, respectively; (P = 0.047)). Overall, women were very satisfied; 97.6% would recommend the procedure to a friend and 95.2% happy to consider a repeat procedure in the future if required. The complication rate was 4.8%, and all were minor in nature. CONCLUSION: Operative hysteroscopic procedures can be performed successfully in the outpatient setting using the Myosure Lite device with a high level of patient satisfaction. PMID- 26259640 TI - Homogeneous and heterogeneous finite element models to predict radius bone strength in forward fall configuration. PMID- 26259639 TI - Pharmacological inhibition of lysosomes activates the MTORC1 signaling pathway in chondrocytes in an autophagy-independent manner. AB - Mechanistic target of rapamycin (serine/threonine kinase) complex 1 (MTORC1) is a protein-signaling complex at the fulcrum of anabolic and catabolic processes, which acts depending on wide-ranging environmental cues. It is generally accepted that lysosomes facilitate MTORC1 activation by generating an internal pool of amino acids. Amino acids activate MTORC1 by stimulating its translocation to the lysosomal membrane where it forms a super-complex involving the lysosomal membrane-bound vacuolar-type H(+)-ATPase (v-ATPase) proton pump. This translocation and MTORC1 activation require functional lysosomes. Here we found that, in contrast to this well-accepted concept, in epiphyseal chondrocytes inhibition of lysosomal activity by v-ATPase inhibitors bafilomycin A1 or concanamycin A potently activated MTORC1 signaling. The activity of MTORC1 was visualized by phosphorylated forms of RPS6 (ribosomal protein S6) and EIF4EBP1, 2 well-known downstream targets of MTORC1. Maximal RPS6 phosphorylation was observed at 48-h treatment and reached as high as a 12-fold increase (p < 0.018). This activation of MTORC1 was further confirmed in bone organ culture and promoted potent stimulation of longitudinal growth (p < 0.001). Importantly, the same effect was observed in ATG5 (autophagy-related 5)-deficient bones suggesting a macroautophagy-independent mechanism of MTORC1 inhibition by lysosomes. Thus, our data show that in epiphyseal chondrocytes lysosomes inhibit MTORC1 in a macroautophagy-independent manner and this inhibition likely depends on v-ATPase activity. PMID- 26259641 TI - Prognostic factors in non-small cell lung cancer patients who are recommended to receive single-agent chemotherapy (docetaxel or pemetrexed) as a second- or third line chemotherapy: in the era of oncogenic drivers and molecular-targeted agents. AB - PURPOSE: Docetaxel or pemetrexed monotherapy is recommended either as a second line treatment for non-small cell lung cancer (NSCLC) patients without EGFR mutation or ALK fusion genes or as a third-line treatment for patients with EGFR mutation or ALK fusion. However, efficacy and survival for these two settings have not been compared, leaving it unclear whether these two populations can be included in the same clinical trials. Moreover, prognostic factors for patients who are recommended to receive docetaxel/pemetrexed monotherapy are largely unknown. METHODS: Docetaxel or pemetrexed was administered to 67 EGFR wild-type patients as a second-line treatment following one platinum-based combination chemotherapy and to 17 EGFR mutant patients as a third-line treatment following EGFR tyrosine kinase inhibitors and one platinum-based combination chemotherapy. Docetaxel and pemetrexed were administered at 60 and 500 mg/m(2), respectively, every 3 weeks until disease progression, intolerable toxicity, or patient refusal. Overall survivals (OSs) between the two groups were compared using the log-rank test, and prognostic factors were evaluated via Cox's proportional hazards models. RESULTS: The median OS was 345.5 days in the EGFR wild-type second-line group and 616 days in the EGFR mutant third-line group. Multivariate analyses revealed that the stage before first-line treatment, performance status, and EGFR status were significant prognostic factors. CONCLUSIONS: When planning clinical studies of NSCLC patients recommended to receive docetaxel or pemetrexed as single-agent chemotherapy, the EGFR status and stage before first-line treatment should be considered as stratification factors of randomized clinical studies. PMID- 26259642 TI - Time within reproductive season, but not age or inbreeding coefficient, affects seminal and sperm quality in the whooping crane (Grus americana). AB - All living whooping cranes (Grus americana) are descended from 16 or fewer birds that remained alive in the early 1940s, a bottleneck that puts the species at potential risk for inbreeding depression. Although AI is commonly used in the management of the captive population of this species, little is known about seminal traits or factors affecting sperm quality in the whooping crane. In the present study, semen samples were collected from 29 adult males (age 3-27 years) during the early (March), mid (April) and late (May) breeding season over 2 consecutive years. The effects of donor age, time within reproductive season and level of inbreeding on seminal characteristics were analysed using regression and information-theoretic model selection. Only time within reproductive season significantly affected seminal traits, with total numbers of spermatozoa and proportions of pleiomorphisms increasing across the season. We conclude that, even with a highly restricted number of founders, there is no discernible influence of inbreeding (at the levels described) on sperm output or quality. Furthermore, although there is variance in seminal quality, the whooping crane produces significant numbers of motile spermatozoa throughout the breeding season, similar to values reported for the greater sandhill crane (Grus canadensis tabida). PMID- 26259643 TI - Influence of echinocandin administration on hemodynamic parameters in medical intensive care unit patients: a single center prospective study. AB - PURPOSE: Fungal infections present a constant risk to critically ill and immunocompromised patients. Therefore, treatment guidelines recommend echinocandins as first-line antifungals in critically ill patients to improve patient outcomes. Echinocandins are usually well tolerated; nevertheless, rare adverse events can occur. There are reports of temporary deterioration of hemodynamic parameters during loading doses, especially in critically ill patients. The objective of this study is to analyze the hemodynamic changes during administration of the echinocandin antifungals, caspofungin and anidulafungin, in medical intensive care unit patients. METHODS: A prospective study in medical ICU patients receiving echinocandins was monitored using single indicator transpulmonary thermodilution (TPTD). TPTD measurements were performed immediately before, directly after, and 4 h after echinocandins on two following days. RESULTS: Mean arterial pressure and also diastolic blood pressure showed significant changes (p < 0.042 and p < 0.007) after echinocandin application in the measurement immediately after application, but not after 4 h. Basic hemodynamic parameters as well as the TPTD-derived cardiac function parameters did not significantly change after echinocandin application at all. In patients with the need for norepinephrine therapy, the vasopressor dose was not statistically significantly altered. CONCLUSION: To conclude, administration of echinocandins in this observed study population is safe, even in severely critically ill patients if application rules of these agents are followed. However, adverse effects could be observed and practitioners should be cognizant of these effects. These observations can be optimized by high-level assessments, such as the pulse contour cardiac output monitoring, and clinicians should continue to be vigilant with cardiac monitoring of patients receiving echinocandin antifungals. PMID- 26259645 TI - Low birthweight increases risk for cardiovascular disease hospitalisations in a remote Indigenous Australian community--a prospective cohort study. AB - OBJECTIVES: To investigate the association between low birthweight (LBW; <2,500 grams) and cardiovascular disease (CVD) hospitalisations in adult life in a remote Indigenous Australian community. METHODS: This was a prospective cohort of 852 participants with recorded birthweight using community-wide health screening examinations conducted between 1992 and 1999 and hospitalisation records up to 2012. Cox proportional hazard models assessed the association between LBW and hypertension, major CVD (heart failure, myocardial infarction and stroke) and any CVD hospitalisations. RESULTS: There were 236 participants (28%) who had a low birthweight. The LBW group had a higher risk of developing any CVD (HR = 1.43, 95%CI 1.01-2.03), major CVD (HR = 1.51, 95%CI 0.93-2.47) and hypertension (HR = 1.83, 95%CI 1.09-2.96) than the normal birthweight (NBW) group (>=2,500 g). Women with LBW had more than 2.6 times the risk of a hospitalisation associated with hypertension compared to their NBW counterparts (HR = 2.61, 95%CI 1.38-4.93), but this relationship was not seen in men. CONCLUSIONS AND IMPLICATIONS: LBW increased the risk of cardiovascular disease hospitalisations in adult life in this group. Further CVD prevention initiatives should continue to include LBW as a key predictor of CVD in this community. The mechanisms of gender influence on the hypertension relationship are unknown and require further investigation in indigenous populations worldwide. PMID- 26259646 TI - Histologic Outcomes of Uninfected Human Immature Teeth Treated with Regenerative Endodontics: 2 Case Reports. AB - A growing body of evidence exists showing the possibility of growing vital tissues in the root canal spaces of teeth with necrotic pulps and open apices. However, there is very limited histologic information regarding characteristics of tissues formed in the root canal space of human teeth after regenerative endodontics. The aim of this study was to examine clinically and histologically the outcomes of human immature teeth treated with regenerative endodontics. Two healthy birooted human maxillary first premolar teeth scheduled for extraction were included. Preoperative radiographs confirmed that these teeth had immature apices. Vitality tests showed the presence of vital pulps in these teeth. After receiving consent forms, the teeth were isolated with a rubber dam, and the pulps were completely removed. After the formation of blood clots in the canals, the teeth were covered with mineral trioxide aggregate. Four months later, the teeth were clinically and radiographically evaluated, extracted, and examined histologically. Both patients remained asymptomatic after treatment. Radiographic examination of the teeth showed signs of root development after treatment. Histologic examination of tissues growing into the root canal space of these teeth shows the presence of connective tissue, bone and cementum formation, and thickening of roots. Based on our findings, it appears that when canals of teeth with open apices are treated with regenerative endodontics, tissues of the periodontium grow into the root canals of these teeth. PMID- 26259647 TI - Bond Strength between Fiber Posts and Root Dentin Treated with Natural Cross linkers. AB - INTRODUCTION: The aim of this study was to investigate the effects of a proanthocyanidin-rich extract (grape seed extract [GSE]) on the bond strength and stability of the adhesion of fiber posts to the root dentine using 2 adhesive systems: a total-etch and a self-etch adhesive system. METHODS: Single-rooted human teeth were randomly divided into 6 groups: G1 (control), untreated + total etch adhesive Adper Scotchbond Multi-Purpose (3M ESPE, St Paul, MN); G2, 6.5% GSE for 5 minutes + SB; G3, 10% GSE for 5 minutes + SB; and G4 to G6 groups were similar to previous ones; however, the self-etch adhesive system Clearfil SE Bond (Kuraray, Kurashiki, Japan) was used. Fiber posts were cemented with RelyX ARC (3M ESPE), and the specimens were immediately tested for push out or stored for 12 months. The bond strength means were analyzed by analysis of variance and Games-Howell post hoc tests (alpha = 0.05). Additionally, matrix metalloproteinase inhibition by 0.65%, 0.065%, and 0.0065% GSE was examined with gelatin zymography. RESULTS: The use of GSE did not affect immediate bond strength to dentin and contributed to preserve the bond strength after 12 months (P < .05) for both adhesives. The bond strength of SB was significantly higher than Clearfil SE Bond (P < .05). Gelatin zymography showed reduced matrix metalloproteinase activity when recombinant enzymes were incubated with both 0.65% and 0.065% GSE, with complete inhibition at the highest concentration. CONCLUSIONS: The pretreatment with GSE can be used as a natural alternative to improve bond strength stability of dentin-adhesive interfaces in root canals. PMID- 26259648 TI - Hepatothorax caused by a late post-traumatic diaphragmatic rupture. PMID- 26259649 TI - The effects of muscle contraction and recombinant osteocalcin on insulin sensitivity ex vivo. AB - We tested whether GPRC6A, the putative receptor of undercarboxylated osteocalcin (ucOC), is present in mouse muscle and whether ucOC increases insulin sensitivity following ex vivo muscle contraction. GPPRC6A is expressed in mouse muscle and in the mouse myotubes from a cell line. ucOC potentiated the effect of ex vivo contraction on insulin sensitivity. INTRODUCTION: Acute exercise increases skeletal muscle insulin sensitivity. In humans, exercise increases circulating ucOC, a hormone that increases insulin sensitivity in rodents. We tested whether GPRC6A, the putative receptor of ucOC, is present in mouse muscle and whether recombinant ucOC increases insulin sensitivity in both C2C12 myotubes and whole mouse muscle following ex vivo muscle contraction. METHODS: Glucose uptake was examined in C2C12 myotubes that express GPRC6A following treatment with insulin alone or with insulin and increasing ucOC concentrations (0.3, 3, 10 and 30 ng/ml). In addition, glucose uptake, phosphorylated (p-)AKT and p-AS160 were examined ex vivo in extensor digitorum longus (EDL) dissected from C57BL/6J wild type mice, at rest, following insulin alone, after muscle contraction followed by insulin and after muscle contraction followed by recombinant ucOC then insulin exposure. RESULTS: We observed protein expression of the likely receptor for ucOC, GPRC6A, in whole muscle sections and differentiated mouse myotubes. We observed reduced GPRC6A expression following siRNA transfection. ucOC significantly increased insulin-stimulated glucose uptake dose-dependently up to 10 ng/ml, in differentiated mouse C2C12 myotubes. Insulin increased EDL glucose uptake (~30 %, p < 0.05) and p-AKT and p-AKT/AKT compared with rest (all p < 0.05). Contraction prior to insulin increased muscle glucose uptake (~25 %, p < 0.05), p-AKT, p-AKT/AKT, p-AS160 and p-AS160/AS160 compared with contraction alone (all p < 0.05). ucOC after contraction increased insulin-stimulated muscle glucose uptake (~12 % p < 0.05) and p-AS160 (<0.05) more than contraction plus insulin alone but without effect on p-AKT. In the absence of insulin and/or of contraction, ucOC had no significant effect on muscle glucose uptake. CONCLUSIONS: GPRC6A, the likely receptor of osteocalcin (OC), is expressed in mouse muscle. ucOC treatment augments insulin-stimulated skeletal muscle glucose uptake in C2C12 myotubes and following ex vivo muscle contraction. ucOC may partly account for the insulin sensitizing effect of exercise. PMID- 26259650 TI - Tracking down the path of memory: eye scanpaths facilitate retrieval of visuospatial information. AB - Recent research points to a crucial role of eye fixations on the same spatial locations where an item appeared when learned, for the successful retrieval of stored information (e.g., Laeng et al. in Cognition 131:263-283, 2014. doi: 10.1016/j.cognition.2014.01.003 ). However, evidence about whether the specific temporal sequence (i.e., scanpath) of these eye fixations is also relevant for the accuracy of memory remains unclear. In the current study, eye fixations were recorded while looking at a checkerboard-like pattern. In a recognition session (48 h later), animations were shown where each square that formed the pattern was presented one by one, either according to the same, idiosyncratic, temporal sequence in which they were originally viewed by each participant or in a shuffled sequence although the squares were, in both conditions, always in their correct positions. Afterward, participants judged whether they had seen the same pattern before or not. Showing the elements serially according to the original scanpath's sequence yielded a significantly better recognition performance than the shuffled condition. In a forced fixation condition, where the gaze was maintained on the center of the screen, the advantage of memory accuracy for same versus shuffled scanpaths disappeared. Concluding, gaze scanpaths (i.e., the order of fixations and not simply their positions) are functional to visual memory and physical reenacting of the original, embodied, perception can facilitate retrieval. PMID- 26259652 TI - How to construct a linguistic landmark: language cues in the formation of hierarchical representations of space. AB - The formation of a hierarchical representation of space can be induced by the spatial adjacency of places marked by landmark objects from the same semantic category, as was demonstrated by a route-planning experiment (Wiener and Mallot in Spat Cogn Comput 3(4):331-358, 2003). Using the same paradigm, we tested the efficiency of linguistic cues with various hierarchical categorization principles in regional structuring. In five different conditions, places of the experimental environment were characterized (1) by landmark objects, (2) by arbitrary proper names on region level, (3) by prototypical names on region level, (4) by nouns from different semantic categories, and (5) by groups of nouns with intrinsic whole-part relation. A region effect comparable to the landmark object condition was found only for the whole-part relations, which combine spatial proximity with a shared context. A linguistic analysis revealed a correspondence to the intended regional subdivision only for the cues of this condition. PMID- 26259651 TI - Numbers in the eye of the beholder: What do eye movements reveal about numerical cognition? AB - The eyes, often called the window to our minds, reveal the focus of spatial attention and are therefore a powerful research tool for the study of spatial processing and spatially related higher cognitive functions. The aim of this paper is to highlight the potential of eye movement analysis in the domain of numerical cognition, to review several relevant findings, and to provide an outlook for future research. PMID- 26259653 TI - MicroRNA-124 suppresses the migration and invasion of osteosarcoma cells via targeting ROR2-mediated non-canonical Wnt signaling. AB - MicroRNAs (miRs) have been implicated in tumorigenesis through inhibition of the expression of their target genes at post-transcriptional levels. miR-124 has been found to be downregulated in many malignant tumors including osteosarcoma (OS). However, the detailed mechanism of miR-124 in the regulation of OS malignant phenotypes remains largely unclear. Here we aimed to explore the role of miR-124 in mediating OS cell migration and invasion, as well as the underlying regulatory mechanisms. Real-time RT-PCR data showed that miR-124 was frequently downregulated in OS cell lines compared to normal human osteoblast cells. We further conducted bioinformatic analysis and a luciferase reporter assay, and identified receptor tyrosine kinase-like orphan receptor 2 (ROR2) as a novel target of miR-124. Furthermore, we found that ROR2 was significantly upregulated in OS cell lines compared to normal human osteoblast cells, and miR-124 negatively mediated the protein level of ROR2 in U-2OS and Saos-2 cells. Moreover, transfection with miR-124 mimics significantly suppressed migration and invasion in the U-2OS and Saos-2 cells, while overexpression of ROR2 in the miR 124-transfected OS cells reversed the inhibitory effect of miR-124 upregulation on OS cell migration and invasion. In addition, we found that overexpression of miR-124 significantly suppressed the activity of non-canonical Wnt signaling, downstream of ROR2. Based on these findings, we suggest that miR-124 may inhibit OS metastasis, partly at least, via targeting ROR2 and thus suppressing the activity of ROR2-mediated non-canonical Wnt signaling. PMID- 26259655 TI - HPLC-ESI-MS/MS of brain neurotransmitter modulator lobeline and related piperidine alkaloids in Lobelia inflata L. AB - There is a renewed interest in lobelia alkaloids because of their activity on the central nervous system. Lobeline, the most active of them, a nicotinic receptor ligand and neurotransmitter transporter inhibitor, is a candidate pharmacotherapy for metamphetamine abuse. In the present work, high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry in positive ion mode was used for investigating the alkaloid profile in Lobelia inflata L. Chromatographic separations were achieved on a Gemini C6-phenyl reversed-phase column providing good peak shape and improved selectivity. Being mostly 2,6-disubstituted piperidines, lobelia alkaloids presented abundant [M + H](+) ions with typical fragmentation. Identification was possible from a few specific ions, especially those resulting from excision of one of the substituents. Based on fragmentation pattern of lobeline as reference compound, 52 alkaloids were identified in the aqueous methanolic extract of L. inflata in contrast to the previously known some 20. Structural variability of these alkaloids identified arises basically from their substituents which can be phenyl 2-ketoethyl- or phenyl-2-hydroxyethyl units as well as their methyl-, ethyl- or propyl- homologues attached in different combinations. Several propyl homologue lobelia alkaloids and five hydroxypiperidine derivatives were found in the plant at the first time. In addition to 8-O-esters of 2-monosubstituted piperidine alkaloids previously reported by us in L. inflata, a 3-hydroxy-3-phenylpropanoic acid ester of hydroxyallosedamine ring-substituted was also identified as a new natural product. High-performance liquid chromatography-electrospray ionization tandem mass spectrometry can be successfully applied to Lobeliacae plant samples in the routine screening for new and known bioactive constituents, quality control of the crude drug, lobelia herba, alkaloid production studies, breeding and chemotaxonomy. PMID- 26259654 TI - Linking molecular models with ion mobility experiments. Illustration with a rigid nucleic acid structure. AB - Ion mobility spectrometry experiments allow the mass spectrometrist to determine an ion's rotationally averaged collision cross section Omega(EXP). Molecular modelling is used to visualize what ion three-dimensional structure(s) is(are) compatible with the experiment. The collision cross sections of candidate molecular models have to be calculated, and the resulting Omega(CALC) are compared with the experimental data. Researchers who want to apply this strategy to a new type of molecule face many questions: (1) What experimental error is associated with Omega(EXP) determination, and how to estimate it (in particular when using a calibration for traveling wave ion guides)? (2) How to generate plausible 3D models in the gas phase? (3) Different collision cross section calculation models exist, which have been developed for other analytes than mine. Which one(s) can I apply to my systems? To apply ion mobility spectrometry to nucleic acid structural characterization, we explored each of these questions using a rigid structure which we know is preserved in the gas phase: the tetramolecular G-quadruplex [dTGGGGT]4, and we will present these detailed investigation in this tutorial. PMID- 26259656 TI - Laser desorption/ionization mass spectrometry of dye-sensitized solar cells: identification of the dye-electrolyte interaction. AB - Dye-sensitized solar cells (DSCs) have great potential to provide sustainable electricity from sunlight. The photoanode in DSCs consists of a dye-sensitized metal oxide film deposited on a conductive substrate. This configuration makes the photoanode a perfect sample for laser desorption/ionization mass spectrometry (LDI-MS). We applied LDI-MS for the study of molecular interactions between a dye and electrolyte on the surface of a TiO2 photoanode. We found that a dye containing polyoxyethylene groups forms complexes with alkali metal cations from the electrolyte, while a dye substituted with alkoxy groups does not. Guanidinium ion forms adducts with neither of the two dyes. PMID- 26259657 TI - Comparison of sulfo-conjugated and gluco-conjugated urinary metabolites for detection of methenolone misuse in doping control by LC-HRMS, GC-MS and GC-HRMS. AB - Methenolone (17beta-hydroxy-1-methyl-5alpha-androst-1-en-3-one) misuse in doping control is commonly detected by monitoring the parent molecule and its metabolite (1-methylene-5alpha-androstan-3alpha-ol-17-one) excreted conjugated with glucuronic acid using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography mass spectrometry (LC-MS) for the parent molecule, after hydrolysis with beta-glucuronidase. The aim of the present study was the evaluation of the sulfate fraction of methenolone metabolism by LC-high resolution (HR)MS and the estimation of the long-term detectability of its sulfate metabolites analyzed by liquid chromatography tandem mass spectrometry (LC-HRMSMS) compared with the current practice for the detection of methenolone misuse used by the anti-doping laboratories. Methenolone was administered to two healthy male volunteers, and urine samples were collected up to 12 and 26 days, respectively. Ethyl acetate extraction at weak alkaline pH was performed and then the sulfate conjugates were analyzed by LC-HRMS using electrospray ionization in negative mode searching for [M-H](-) ions corresponding to potential sulfate structures (comprising structure alterations such as hydroxylations, oxidations, reductions and combinations of them). Eight sulfate metabolites were finally detected, but four of them were considered important as the most abundant and long term detectable. LC clean up followed by solvolysis and GC/MS analysis of trimethylsilylated (TMS) derivatives reveal that the sulfate analogs of methenolone as well as of 1-methylene-5alpha-androstan-3alpha-ol-17-one, 3z hydroxy-1beta-methyl-5alpha-androstan-17-one and 16beta-hydroxy-1-methyl-5alpha androst-1-ene-3,17-dione were the major metabolites in the sulfate fraction. The results of the present study also document for the first time the methenolone sulfate as well as the 3z-hydroxy-1beta-methyl-5alpha-androstan-17-one sulfate as metabolites of methenolone in human urine. The time window for the detectability of methenolone sulfate metabolites by LC-HRMS is comparable with that of their hydrolyzed glucuronide analogs analyzed by GC-MS. The results of the study demonstrate the importance of sulfation as a phase II metabolic pathway for methenolone metabolism, proposing four metabolites as significant components of the sulfate fraction. PMID- 26259658 TI - Analysis of sexual assault evidence: statistical classification of condoms by ambient mass spectrometry. AB - Desorption electrospray ionization mass spectrometry (DESI-MS) and easy ambient sonic-spray ionization mass spectrometry (EASI-MS) are employed here in the forensic analysis of chemical compounds found in condoms and relative traces, and their analytical performances are compared. Statistical analysis of data obtained from mass spectra only was applied in order to obtain classification rules for distinguishing ten types of condoms. In particular, two supervised chemometric techniques [linear discriminant analysis (LDA) and soft independent modeling of class analogy (SIMCA)] were carried out on absolute and relative intensity values to test the performances of statistical models in terms of predictive capacity. The achieved classification of samples was excellent because of the high prediction percentages of the method used both for DESI and EASI mass spectrometry analyses, confirming these two as potential ambient ionization techniques for forensic analyses in case of sexual assault crimes. EASI-MS showed 99% prediction ability for LDA using relative data and 100% prediction ability for SIMCA using both absolute and relative ones, while DESI showed 94% prediction ability for both LDA and SIMCA. The absence of any sample preparation technique gives advantages in terms of sample preservation and reduced contamination, allowing successive analyses to be performed on the same sample by other techniques. PMID- 26259659 TI - Identification of two arginine kinase forms of endoparasitoid Leptomastix dactylopii venom by bottom up-sequence tag approach. AB - Leptomastix dactylopii (Howard) is an endoparasitoid wasp, natural enemy of mealybug Planococcus citri (Risso). Despite the acquired knowledge regarding this host-parasitoid interaction, only little information is available on the factors of parasitoid origin able to modulate the mealybug physiology. The major alteration observed in P. citri is a strong reduction in fecundity, which is evident soon after parasitization by L. dactylopii or venom injection in unparasitized hosts indicating that this proteinaceus secretion injected at the oviposition plays a key-role in host regulation. Protein identification of L. dactilopii venom has been limited by the lack of literature sources and public protein databases. Here, we identified two venom proteins by an integrated trascriptomic and proteomic approach. A custom-made transcriptomic database from the L. dactylopii venom glands was created by applying the high-throughput RNA sequencing approach. Two-dimensional gel electrophoresis (2DE) trypsinized protein spots were analyzed by high-resolution mass spectrometry (FTICRMS-12 T). The most abundant peptide ions were fragmented by collision induced dissociation and the obtained sequence tags were subjected to custom-made protein database searching. Two putative arginine kinases (full-length and truncated form) were identified. This is the first case in which both, truncated and full length arginine kinases, are identified in an endoparasitoid non-paralyzing venom. PMID- 26259660 TI - A sample preparation method for recovering suppressed analyte ions in MALDI TOF MS. AB - In matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS), analyte signals can be substantially suppressed by other compounds in the sample. In this technical note, we describe a modified thin layer sample preparation method that significantly reduces the analyte suppression effect (ASE). In our method, analytes are deposited on top of the surface of matrix preloaded on the MALDI plate. To prevent embedding of analyte into the matrix crystals, the sample solution were prepared without matrix and efforts were taken not to re-dissolve the preloaded matrix. The results with model mixtures of peptides, synthetic polymers and lipids show that detection of analyte ions, which were completely suppressed using the conventional dried droplet method, could be effectively recovered by using our method. Our findings suggest that the incorporation of analytes in the matrix crystals has an important contributory effect on ASE. By reducing ASE, our method should be useful for the direct MALDI MS analysis of multicomponent mixtures. PMID- 26259661 TI - Characterization of N,N-dimethyl amino acids by electrospray ionization-tandem mass spectrometry. AB - Methylation is an essential metabolic process for a number of critical reactions in the body. Methyl groups are involved in the healthy function of the body life processes, by conducting methylation process involving specific enzymes. In these processes, various amino acids are methylated, and the occurrence of methylated amino acids in nature is diverse. Nowadays, mass-spectrometric-based identification of small molecules as biomarkers for diseases is a growing research. Although all dimethyl amino acids are metabolically important molecules, mass spectral data are available only for a few of them in the literature. In this study, we report synthesis and characterization of all dimethyl amino acids, by electrospray ionization-tandem mass spectrometry (MS/MS) experiments on protonated molecules. The MS/MS spectra of all the studied dimethyl amino acids showed preliminary loss of H2O + CO to form corresponding immonium ions. The other product ions in the spectra are highly characteristic of the methyl groups on the nitrogen and side chain of the amino acids. The amino acids, which are isomeric and isobaric with the studied dimethyl amino acids, gave distinctive MS/MS spectra. The study also included MS/MS analysis of immonium ions of dimethyl amino acids that provide information on side chain structure, and it is further tested to determine the N-terminal amino acid of the peptides. PMID- 26259664 TI - Prognostic Factors and Clinical Characteristics for Hepatocellular Carcinoma Patients with Benign Enlarged Perihepatic Lymph Nodes: a Single-Center Experience from China. AB - BACKGROUND: The clinical and prognostic significance of benign perihepatic lymph nodes enlargement (PLNE) from patients with hepatocellular carcinoma (HCC) remains unclear. The objective of this study is to evaluate the relative frequency, incidence and locations of benign PLNE, and the impact on long-term survival of the patients. METHODS: A total of 219 consecutive patients who underwent curative resection of HCC between July 2006 and March 2012 in our single institution were divided into two groups according to the presence of PLNE: PLNE group (n = 76), and control group (n = 143). The long-term outcomes were evaluated and compared between the two groups. RESULTS: The 1-, 3-, and 5 year recurrence-free survival rates were 77.2, 60.0, and 38.1 % in the PLNE group and 71.3, 42.5, and 25.0 % in the control group (p = 0.080). Corresponding overall survival rates were 96.0, 84.8, 67.1 % and 93.5, 72.4, 46.9 % respectively (p = 0.041). Patients with benign PLNE were associated with a higher rate of centrally located HCCs or tumors adjacent to the major branch of vascular vessels. Multivariate analysis revealed that benign PLNE was an independent positive prognostic factor affecting the overall survival. CONCLUSIONS: According to our analysis, patients of HCC with benign PLNE after curative resection can be expected to have better long-term survival. It is also associated with a lower risk of tumor recurrence, but not significant. This finding may provide new insights into daily clinical practice and the pathophysiological characteristics of HCC development. PMID- 26259665 TI - Close surgical margins after radical prostatectomy mimic biochemical recurrence rates of positive margins. AB - INTRODUCTION: The significance of a "close" but negative surgical margin after radical prostatectomy (RP) is controversial. We evaluated the effect of a close surgical margin (CSM) on biochemical recurrence (BCR) compared to a negative margin after RP. MATERIALS AND METHODS: Pathologic records of men who underwent RP from 2005-2011 were retrospectively reviewed. Margin status was classified as "positive" (PSM), "negative" (NSM), or "close" (<1mm from margin). BCR was defined as 2 consecutive postoperative prostate specific antigen measurements >0.2ng/ml. Probability of BCR was estimated using the Kaplan-Meier method and stratified by margin status. Univariable and multivariable Cox proportional hazards models were used to determine whether close margin status was associated with an increased rate of BCR. RESULTS: A total of 609 consecutive patients underwent RP (93% robotic) and had complete pathologic data. A total of 126 (20.7%) had PSM, 453 (74.4%) had NSM, and 30 (4.9%) had CSM (mean<0.44mm). The 3 year BCR-free survival for patients with CSM was similar to those with PSM (70.4% vs. 74.5%, log rank P = 0.66) and significantly worse than those with NSM (90%, log rank P<0.001). On multivariable regression, positive margin status (HR = 3.26, P<0.001) was significantly associated with a higher risk of BCR, along with close margins (HR = 2.7, P = 0.04). CONCLUSIONS: BCR for patients with CSM at RP is tantamount to PSM patients. CSM <1mm should be explicitly noted on pathology reports. Patients with this finding should be followed up closely and offered adjuvant therapy. PMID- 26259666 TI - Multiparametric magnetic resonance imaging-transrectal ultrasound fusion-assisted biopsy for the diagnosis of local recurrence after radical prostatectomy. AB - OBJECTIVE: Approximately 15% of patients who undergo radical prostatectomy (RP) for prostate cancer develop local recurrence, which is heralded by a rise in serum prostate-specific antigen (PSA) levels. Early detection and treatment of recurrence improves the outcome of salvage treatment. We investigated the ability of multiparametric magnetic resonance imaging (mpMRI)-transrectal ultrasound (TRUS) fusion-guided biopsy (FGB) combined with "cognitive biopsy" to confirm local recurrence of prostate cancer after RP. MATERIALS AND METHODS: In this retrospective study conducted between January 2010 and December 2014, patients with rising PSA levels after RP who had no known evidence of distant metastases underwent mpMRI including T2-weighted (T2W) imaging, diffusion-weighted imaging, dynamic contrast-enhanced (DCE) MRI at 3 Tesla, and subsequent MRI-ultrasound fusion biopsy with cognitive assistance. The detection rate of locally recurrent disease was determined. RESULTS: A total of 10 patients (mean age = 67y, mean PSA level = 3.44ng/ml) met the inclusion criteria. Of the 10 patients, all had positive findings suspicious for local recurrence on mpMRI per entrance criterion. The most important features on mpMRI were early enhancement on DCE MR images and hypointensity on T2W images. The average lesion diameter on mpMRI was 1.12cm (range: 0.40-2.20cm). All suspicious lesions (16/16, 100%) were positive on T2W MR images, 14 (89%) showed positive features on apparent diffusion coefficient maps of diffusion-weighted images, and 16 (100%) were positive on DCE MR images. MRI-TRUS FGBs were positive in 10/16 lesions (62.5%) and 8/10 (80%) patients. CONCLUSION: MRI-TRUS FGB with cognitive assistance is able to detect and diagnose locally recurrent lesions after RP, even at low PSA levels. This may facilitate early detection of recurrent disease and improve salvage treatment outcomes. PMID- 26259667 TI - Expression of the Helicobacter pylori virulence factor vacuolating cytotoxin A (vacA) is influenced by a potential stem-loop structure in the 5' untranslated region of the transcript. AB - The vacuolating cytotoxin, VacA, is an important virulence factor secreted by the gastric pathogen Helicobacter pylori. Certain vacA genotypes are strongly associated with disease risk, but the association is not absolute. The factors determining vacA gene expression are not fully understood, and the mechanisms of its regulation are elusive. We have identified a potential mRNA stem-loop forming structure in the 5' untranslated region (UTR) of the vacA transcript. Using site directed mutagenesis, we found that disruption of the stem-loop structure reduced steady-state mRNA levels between two- and sixfold (P = 0.0005) and decreased mRNA half-life compared with wild type (P = 0.03). This led to a marked reduction in VacA protein levels and overall toxin activity. Additionally, during stressful environmental conditions of acid pH or high environmental salt concentrations, when general transcription of vacA was decreased or increased respectively, the stabilising effects of the stem-loop were even more pronounced. Our results suggest that the stem-loop structure in the vacA 5' UTR is an important determinant of vacA expression through stabilisation of the vacA mRNA transcript and that the stabilising effect is of particular importance during conditions of environmental stress. PMID- 26259668 TI - Chronic low back pain and disability in Brazilian jiu-jitsu athletes. AB - OBJECTIVES: To identify the prevalence of chronic low back pain (CLBP) and functional disability in Brazilian jiu-jitsu athletes. STUDY DESIGN: Cross sectional, observational. SETTINGS: The study was conducted at jiu-jitsu training sites in the State of Rio de Janeiro. MAIN OUTCOME MEASURES: Presence of Chronic low back pain and Quebec Back Pain Disability Scale. RESULTS: The sample was composed of 72 athletes (mean age of 26.7), being 36 recreational and 36 professional. Chronic low back pain was present in 80.6% of athletes. Pain was present in 88.9% of professional and 72.2% of recreational athletes. In the professional jiu-jitsu group, the median of the Quebec Back Pain Disability Scale (QBPDS) was 10 (IQR = 16), and in the recreational group the QBPDS result was 6.0 (IQR = 12) (p = .001). Professional athletes had a marginally significant increased risk of developing CLBP [OR = 3.0; CI(95%) 0.8-10.9)]. CONCLUSION: The prevalence of low back pain in jiu-jitsu practice was high and professional athletes seem to have a high risk of developing CLBP. PMID- 26259669 TI - The genomics of organismal diversification illuminated by adaptive radiations. AB - Adaptive radiation is the rapid and extensive ecological diversification of an organismal lineage to generate both phenotypic disparity (divergence) and similarity (convergence). Demonstrating particularly clear evidence of the power of natural selection, adaptive radiations serve as outstanding systems for studying the mechanisms of evolution. We review how the first wave of genomic investigation across major archetypal adaptive radiations has started to shed light on the molecular basis of adaptive diversification. Notably, these efforts have not yet identified consistent features of genomic architecture that promote diversification. However, access to a pool of ancient adaptive variation via genetic exchange emerges as an important driver of adaptive radiation. We conclude by highlighting avenues for future research on adaptive radiations, including the discovery of 'adaptation genes' based on genome scans using replicate convergent populations. PMID- 26259670 TI - Why the activity of a gene depends on its neighbors. AB - Sixty years ago, the position of a gene on a chromosome was seen to be a major determinant of gene activity; however, position effects are rarely central to current discussions of gene expression. We describe a comprehensive and simplifying view of how position in 1D sequence and 3D nuclear space underlies expression. We suggest that apparently-different regulatory motifs including enhancers, silencers, insulators, barriers, and boundaries act similarly - they are active promoters that tether target genes close to, or distant from, appropriate transcription sites or 'factories'. We also suggest that any active transcription unit regulates the firing of its neighbors - and thus can be categorized as one or other type of motif; this is consistent with expression quantitative trait loci (eQTLs) being widely dispersed. PMID- 26259671 TI - Blocking of the PD-1/PD-L1 Interaction by a D-Peptide Antagonist for Cancer Immunotherapy. AB - Blockade of the protein-protein interaction between the transmembrane protein programmed cell death protein 1 (PD-1) and its ligand PD-L1 has emerged as a promising immunotherapy for treating cancers. Using the technology of mirror image phage display, we developed the first hydrolysis-resistant D-peptide antagonists to target the PD-1/PD-L1 pathway. The optimized compound (D) PPA-1 could bind PD-L1 at an affinity of 0.51 MUM in vitro. A blockade assay at the cellular level and tumor-bearing mice experiments indicated that (D) PPA-1 could also effectively disrupt the PD-1/PD-L1 interaction in vivo. Thus D-peptide antagonists may provide novel low-molecular-weight drug candidates for cancer immunotherapy. PMID- 26259672 TI - Thermodynamic constraints on the utility of ecological stoichiometry for explaining global biogeochemical patterns. AB - Carbon and nitrogen cycles are coupled through both stoichiometric requirements for microbial biomass and dissimilatory metabolic processes in which microbes catalyse reduction-oxidation reactions. Here, we integrate stoichiometric theory and thermodynamic principles to explain the commonly observed trade-off between high nitrate and high organic carbon concentrations, and the even stronger trade off between high nitrate and high ammonium concentrations, across a wide range of aquatic ecosystems. Our results suggest these relationships are the emergent properties of both microbial biomass stoichiometry and the availability of terminal electron acceptors. Because elements with multiple oxidation states (i.e. nitrogen, manganese, iron and sulphur) serve as both nutrients and sources of chemical energy in reduced environments, both assimilative demand and dissimilatory uses determine their concentrations across broad spatial gradients. Conceptual and quantitative models that integrate rather than independently examine thermodynamic, stoichiometric and evolutionary controls on biogeochemical cycling are essential for understanding local to global biogeochemical patterns. PMID- 26259673 TI - Natalizumab treatment reduces L-selectin (CD62L) in CD4+ T cells. AB - BACKGROUND: The purpose of this research was to validate the low expression of L selectin (CD62L) in natalizumab (NTZ)-treated patients. CD62L is involved in rolling and transmigration of leukocyte cells. A correlation between CD62LCD4+ T cells low expression and progressive multifocal leukoencephalopathy (PML) development has been suggested in multiple sclerosis (MS) patients treated with NTZ. METHODS: We performed a flow cytometric analysis on peripheral blood mononuclear cells (PBMC); we collected from 23 healthy donors and 225 MS patients: untreated (n = 19) or treated with NTZ (n = 113), interferon-beta (n = 26), glatiramer acetate (n = 26), fingolimod (n = 23) and rituximab (n = 18). We have also analysed two PML/IRIS (immune reconstitution inflammatory syndrome) patients and four longitudinal samples of a NTZ-treated patients before and during the development of a clinical asymptomatic magnetic resonance imaging (MRI) lesion confirmed as PML by cerebrospinal fluid (CSF) examination. Thirty five NTZ-treated patients were studied longitudinally with three samples taken 4 months apart. RESULTS: The NTZ-treated patients showed a lower percentage of CD62L (33.68%, n = 113) than first-line treated patients (44.24%, n = 52, p = 0.0004). NTZ effect was already clear during the first year of treatment (34.68 ; p = 0.0184); it persisted in the following years and disappeared after drug withdrawal (44.08%). Three percent of longitudinally analysed patients showed a percentage of CD62LCD4+ T cells under a hypothetical threshold and one patient with asymptomatic PML belongs to a group which expressed low percentage of CD62LCD4+ T cells. CONCLUSIONS: Our research confirms that NTZ has a specific effect on CD62LCD4+ T cells consisting in decreasing of the number of positive cells. The low level of CD62L found in a clinically asymptomatic PML patient strengthens its potential usefulness as a biomarker of high PML risk in NTZ treated patients. A larger study is required to better confirm the data. PMID- 26259674 TI - Electrocardiograms during Preparticipation Athletic Evaluations: Is the Selective Use a Compromise to Mass Screening? PMID- 26259675 TI - Acceptability of Uncoated Mini-Tablets in Neonates--A Randomized Controlled Trial. AB - OBJECTIVE: To evaluate the suitability of drug-free solid dosage forms (2 mm mini tablets) as an alternative administration modality in neonates in comparison with syrup. STUDY DESIGN: A total of 151 neonates (inpatients; aged 2-28 days; median 4 days) were recruited. An open, randomized, prospective cross-over study was conducted to compare the acceptability and swallowability of 2 mm uncoated mini tablets compared with .5 mL syrup. RESULTS: All neonates (N = 151) accepted the uncoated mini-tablet as well as the syrup (both formulations 100%; 95% CI 97.6% 100.0%; primary objective). The level of swallowability of uncoated mini-tablets was not inferior (P < .0001), in fact even higher (difference in proportions 10.0%; 95% CI 1.37%-19.34%; P = .0315) compared with syrup. Both pharmaceutical formulations were well tolerated, and in none of the 151 neonates, serious adverse events occurred; particularly none of the neonates inhaled or coughed in either of the formulations. CONCLUSIONS: The administration of uncoated mini tablets proved to be a valuable alternative to syrup for term neonates. Our data on neonates close the age gap of prior findings in toddlers and infants: uncoated mini-tablets offer the potential of a single formulation for all age groups. These findings further shift the paradigm from liquid toward small-sized solid drug formulations for children of all age groups, as the World Health Organization proposes. TRIAL REGISTRATION: German Clinical Trials Register (Deutsches Register Klinischer Studien [DRKS; germanctr.de]): DRKS00005609. PMID- 26259676 TI - Effect of ultraviolet-A radiation on the production of Leptolegnia chapmanii (Saprolegniales: Saprolegniaceae) zoospores on dead Aedes aegypti (Diptera: Culicidae) larvae and their larvicidal activity. AB - Impact of UV-radiation in entomopathogens in aquatic environments remains little investigated. The present study reports on the effect of UV-A on the larvicidal activity of Leptolegnia chapmanii zoospores in Aedes aegypti; on the production of zoospores in larvae killed by the pathogen and then exposed to UV-A; and on the activity of these zoospores against healthy larvae. Whereas the virulence of free zoospores in A. aegypti larvae was affected by a UV-A exposure time longer than 10min, production of zoospores in larvae and their virulence were not hampered at a maximal 8h exposure of dead larvae to UV-A. Findings suggest that dead larvae and zoosporangia provide a certain protection to zoospores against UV A and emphasize the susceptibility of free encysted zoospores to such radiation. PMID- 26259677 TI - FGFR1 and FGFR2 in fibrolamellar carcinoma. AB - AIMS: Fibrolamellar carcinoma is characterized by a recurrent DNAJB1-PRKACA chimeric transcript. The functional properties of the fusion are unknown, but are believed to include PRKACA up-regulation. PRKCA is a subunit of protein kinase A. The downstream targets of protein kinase A are unknown, but may include interactions with fibroblast growth factor receptor (FGFR) pathways. In addition, inhibitors for FGFR proteins have been developed recently. METHODS AND RESULTS: Nineteen histologically confirmed fibrolamellar carcinomas were studied. All showed the characteristic DNAJB1-PRKACA transcript by reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemistry for FGFR1 was negative in 19 of 19 cases using a monoclonal antibody, while a polyclonal antibody showed no expression (n = 11) or weak and focal expression (n = 8). RNAin-situ hybridization was 2+ in two cases, 1+ in four cases and negative in four cases. FGFR1 fluorescence in-situ hybridization (FISH) revealed polysomy of chromosome 8 in 17 of 19 cases. Break-apart FISH for FGFR2 was negative for rearrangements in 12 of 12 informative cases. CONCLUSIONS: Fibrolamellar carcinomas show polysomy of chromosome 8 and the FGFR1 locus, and only modest mRNA expression and weak or absent expression at the protein level. FGFR2 rearrangement was not detected. These data reduce the likelihood that FGFR inhibitors will be effective in the treatment of most fibrolamellar carcinomas. PMID- 26259678 TI - Comparative thorax morphology of death-feigning flightless cryptorhynchine weevils (Coleoptera: Curculionidae) based on 3D reconstructions. AB - The thorax morphology, especially the muscles and the tracheal system of three flightless species of Cryptorhynchinae is examined by digital 3D reconstructions based on synchrotron X-ray microtomography and compared to other Curculionidae. Wings, metanepisternites, and muscles functional in flight are fully reduced in the species examined: Kyklioacalles roboris (Curtis), Trigonopterus scharfi Riedel and Trigonopterus vandekampi Riedel. All three share the same set of thoracic muscles, but differences exist in the shape and size of muscles. Both Trigonopterus species examined have a conspicuous fan-shaped branch of Musculus mesosterni primus contracting pro- and mesothorax, interpreted as an adaption to their thanatosis defense strategy. Trigonopterus vandekampi furthermore shows a marked increase in the size of two metacoxal muscles, which may be functional in this species' thanatosis blocking mechanisms. The metathoracic spiracle of all Trigonopterus species is located at the side of the metaventrite externally and not in the subelytral space as in other beetles. It is hypothesized that this translocation was triggered by the need to improve oxygen supply during thanatosis, when both the mesothoracic spiracle and the subelytral cavity are tightly sealed from the outside. PMID- 26259679 TI - The elimination of an adult segment by the Hox gene Abdominal-B. AB - Hox gene activity leads to morphological diversity of organs or structures in different species. One special case of Hox function is the elimination of a particular structure. The Abdominal-B Hox gene of Drosophila melanogaster provides an example of such activity, as this gene suppresses the formation of the seventh abdominal segment in the adult. This elimination occurs only in males, and is characteristic of more advanced Diptera. The elimination requires the differential expression or activity of genes that are downstream Abdominal-B, or that work together with it, and which regulate cell proliferation or cell extrusion. Here, we review the mechanisms responsible for such elimination and provide some new data on processes taking place within this segment. PMID- 26259680 TI - Expansion of the polycomb system and evolution of complexity. AB - Polycomb group (PcG) proteins regulate and maintain expression pattern of genes set early during development. Although originally isolated as regulators of homeotic genes, PcG members play a key role in epigenetic mechanisms that maintain the expression state of a large number of genes. All members of the two polycomb repressive complexes (PRC1 and PRC2) are conserved during evolution and while invertebrates generally have one gene for each of these, vertebrates have multiple homologues of them. It remains unclear, however, if different vertebrate PcG homologues have distinct or overlapping functions. We have identified and compared the sequence of PcG homologues in various organisms to analyze similarities and differences that shaped the evolutionary history of these proteins. Comparative analysis of the sequences led to the identification of several novel and signature motifs in the vertebrate homologues of these proteins, which can be directly used to pick respective homologues. Our analysis shows that PcG is an ancient gene group dating back to pre-bilaterian origin that has not only been conserved but also expanded during the evolution of complexity. The presence of unique motifs in each paralogue and its conservation for more than 500 Ma indicates their functional relevance and probable unique role. Although this does not rule out completely any overlapping function, our finding that these homologues only minimally overlap in their nuclear localization suggests that each PcG homologue has distinct function. We further propose distinct complex formation by the PcG members. Taken together, our studies suggest non-redundant and specific role of multiple homologues of PcG proteins in vertebrates and indicate major expansion event preceded by emergence of vertebrates that contributed as enhanced epigenetic resource to the evolution of complexity. PMID- 26259681 TI - Antimicrobial resistance genes in marine bacteria and human uropathogenic Escherichia coli from a region of intensive aquaculture. AB - Antimicrobials are heavily used in Chilean salmon aquaculture. We previously found significant differences in antimicrobial-resistant bacteria between sediments from an aquaculture and a non-aquaculture site. We now show that levels of antimicrobial resistance genes (ARG) are significantly higher in antimicrobial selected marine bacteria than in unselected bacteria from these sites. While ARG in tetracycline- and florfenicol-selected bacteria from aquaculture and non aquaculture sites were equally frequent, there were significantly more plasmid mediated quinolone resistance genes per bacterium and significantly higher numbers of qnrB genes in quinolone-selected bacteria from the aquaculture site. Quinolone-resistant urinary Escherichia coli from patients in the Chilean aquacultural region were significantly enriched for qnrB (including a novel qnrB gene), qnrS, qnrA and aac(6')-1b, compared with isolates from New York City. Sequences of qnrA1, qnrB1 and qnrS1 in quinolone-resistant Chilean E. coli and Chilean marine bacteria were identical, suggesting horizontal gene transfer between antimicrobial-resistant marine bacteria and human pathogens. PMID- 26259683 TI - Two Pairs of Enantiomeric Alkaloid Dimers from Macleaya cordata. AB - Two pairs of enantiomeric alkaloid dimers, (+/-)-macleayins A (1) and B (2), representing a novel dimerization pattern of two different types of alkaloids via a C-C sigma-bond, were isolated from the aerial parts of Macleaya cordata. The enantiomeric separation was achieved by chiral chromatography. Their structures and stereochemistry were determined by the analysis of extensive spectroscopic data, electronic circular dichroism calculation, and single-crystal X-ray diffraction data. (-)-Macleayin A exhibits modest cytotoxic activity against HL 60 cell line with the IC50 value of 3.51 MUM. PMID- 26259684 TI - Integration of public health and primary care: A systematic review of the current literature in primary care physician mediated childhood obesity interventions. AB - INTRODUCTION: Childhood obesity, with its growing prevalence, detrimental effects on population health and economic burden, is an important public health issue in the United States and worldwide. There is need for expansion of the role of primary care physicians in obesity interventions. The primary aim of this review is to explore primary care physician (PCP) mediated interventions targeting childhood obesity and assess the roles played by physicians in the interventions. METHODS: A systematic review of the literature published between January 2007 and October 2014 was conducted using a combination of keywords like "childhood obesity", "paediatric obesity", "childhood overweight", "paediatric overweight", "primary care physician", "primary care settings", "healthcare teams", and "community resources" from MEDLINE and CINAHL during November 2014. Author name(s), publication year, sample size, patient's age, study and follow-up duration, intervention components, role of PCP, members of the healthcare team, and outcomes were extracted for this review. RESULTS: Nine studies were included in the review. PCP-mediated interventions were composed of behavioural, education and technological interventions or a combination of these. Most interventions led to positive changes in Body Mass Index (BMI), healthier lifestyles and increased satisfaction among parents. PCPs participated in screening and diagnosing, making referrals for intervention, providing nutrition counselling, and promoting physical activity. PCPs, Dietitians and nurses were often part of the healthcare team. CONCLUSION: PCP-mediated interventions have the potential to effectively curb childhood obesity. However, there is a further need for training of PCPs, and explain new types of interventions such as the use of technology. PMID- 26259685 TI - Fat may affect magnetic resonance signal intensity and brain tissue volumes. AB - Obesity/overweight is reported to affect MR-measured brain tissue volume and white matter (WM) signal intensity. This study investigated possible effects of fat on these measures, using pig fat on three participants at a 4T magnet. Grey matter volumes in the presence of fat were lower than baseline measures. Total WM volumes in the presence of fat were higher than baseline measures. WM hypo intensities on T1-weighted images were higher in the presence of fat than baseline measures. Therefore physical effects of head fat of obese/overweight individual may at least, partly contribute to the association of obesity/overweight with MR structural measures. PMID- 26259686 TI - Bioflocculant from pre-treated sludge and its applications in sludge dewatering and swine wastewater pretreatment. AB - Potentials of alkaline-thermal (ALT) pre-treated sludge as a bioflocculant were studied in sludge dewatering and swine wastewater pretreatment. When incubated with this ALT pre-treated sludge, dry solids (DS) and specific resistance to filtration (SRF) of typical wastewater activated sludge reached 22.5% and 3.4*10(12)m/kg, respectively, which were much better than that obtained with conventional chemical flocculants. Sludge dewatering was further improved when both the bioflocculant and conventional polyaluminum chloride (PAC) were used simultaneously. Charge neutralization and inter-particle bridging were proposed as the reasons for the enhanced performance in the case of the combined use. With swine wastewater, the bioflocculant could remove COD, ammonium and turbidity by 45.2%, 41.8% and 74.6% when incubated with 20mg/L at pH 8.0. This study suggested that the ALT pre-treated sludge has a great potential as an alternative bioflocculant to conventional flocculants in sludge dewatering and swine wastewater pretreatment. PMID- 26259687 TI - Cu(II)-Mediated C(sp(2))-H Hydroxylation. AB - A Cu(II)-mediated ortho-C-H hydroxylation using a removable directing group has been developed. The reaction exhibits considerable functional group tolerance. The use of O2 as an oxidant is crucial for the reactivity. Water is also found to significantly improve this reaction. PMID- 26259688 TI - MicroRNA-9 induces defective trafficking of Nav1.1 and Nav1.2 by targeting Navbeta2 protein coding region in rat with chronic brain hypoperfusion. AB - BACKGROUND: Previous studies have demonstrated that the trafficking defects of Nav1.1/Nav1.2 are involved in the dementia pathophysiology. However, the detailed mechanisms are not fully understood. Moreover, whether the impaired miRNAs regulation linked to dementia is a key player in sodium channel trafficking disturbance remains unclear. The cognitive impairment induced by chronic cerebral ischemia through chronic brain hypoperfusion (CBH) is likely reason to precede dementia. Therefore, our goal in the present study was to examine the role of microRNA-9 (miR-9) in regulating Nav1.1/Nav1.2 trafficking under CBH generated by bilateral common carotid artery occlusion (2VO). RESULTS: The impairment of Nav1.1/Nav1.2 trafficking and decreased expression of Navbeta2 were found in the hippocampi and cortices of rats following CBH generated by bilateral 2VO. MiR-9 was increased in both the hippocampi and cortices of rats following CBH by qRT PCR. Intriguingly, miR-9 suppressed, while AMO-miR-9 enhanced, the trafficking of Nav1.1/Nav1.2 from cytoplasm to cell membrane. Further study showed that overexpression of miR-9 inhibited the Navbeta2 expression by targeting on its coding sequence (CDS) domain by dual luciferase assay. However, binding-site mutation or miR-masks failed to influence Navbeta2 expression as well as Nav1.1/Nav1.2 trafficking process, indicating that Navbeta2 is a potential target for miR-9. Lentivirus-mediated miR-9 overexpression also inhibited Navbeta2 expression and elicited translocation deficits to cell membrane of Nav1.1/Nav1.2 in rats, whereas injection of lentivirus-mediated miR-9 knockdown could reverse the impaired trafficking of Nav1.1/Nav1.2 triggered by 2VO. CONCLUSIONS: We conclude that miR-9 may play a key role in regulating the process of Nav1.1/Nav1.2 trafficking via targeting on Navbeta2 protein in 2VO rats at post transcriptional level, and inhibition of miR-9 may be a potentially valuable approach to prevent Nav1.1/Nav1.2 trafficking disturbance induced by CBH. PMID- 26259690 TI - Simultaneous detection of eight swine reproductive and respiratory pathogens using a novel GeXP analyser-based multiplex PCR assay. AB - A new high-throughput GenomeLab Gene Expression Profiler (GeXP) analyser-based multiplex PCR assay was developed for the detection of eight reproductive and respiratory pathogens in swine. The reproductive and respiratory pathogens include North American porcine reproductive and respiratory syndrome virus (PRRSV NA), classical swine fever virus (CSFV), porcine circovirus 2 (PCV-2), swine influenza virus (SIV) (including H1 and H3 subtypes), porcine parvovirus (PPV), pseudorabies virus (PRV) and Japanese encephalitis virus (JEV). Nine pairs of specific chimeric primers were designed and used to initiate PCRs, and one pair of universal primers was used for subsequent PCR cycles. The specificity of the GeXP assay was examined using positive controls for each virus. The sensitivity was evaluated using serial ten-fold dilutions of in vitro-transcribed RNA from all of the RNA viruses and plasmids from DNA viruses. The GeXP assay was further evaluated using 114 clinical specimens and was compared with real-time PCR/single RT-PCR methods. The specificity of the GeXP assay for each pathogen was examined using single cDNA/DNA template. Specific amplification peaks of the reproductive and respiratory pathogens were observed on the GeXP analyser. The minimum copies per reaction detected for each virus by the GeXP assay were as follows: 1000 copies/MUl for PRV; 100 copies/MUl for CSFV, JEV, PCV-2 and PPV; and 10 copies/MUl for SIV-H1, SIV-H3 and PRRSV-NA. Analysis of 114 clinical samples using the GeXP assay demonstrated that the GeXP assay had comparable detection to real-time PCR/single RT-PCR. This study demonstrated that the GeXP assay is a new method with high sensitivity and specificity for the identification of these swine reproductive and respiratory pathogens. The GeXP assay may be adopted for molecular epidemiological surveys of these reproductive and respiratory pathogens in swine populations. PMID- 26259691 TI - Stability of Pre-Orthodontic Orthognathic Surgery Using Intraoral Vertical Ramus Osteotomy Versus Conventional Treatment. AB - PURPOSE: Postoperative skeletal and dental changes were evaluated in patients with mandibular prognathism who underwent mandibular setback surgery using an intraoral vertical ramus osteotomy (IVRO) with and without presurgical orthodontic treatment. MATERIAL AND METHODS: This retrospective cohort study included consecutive patients with skeletal Class III malocclusions who underwent IVRO. Patients treated with pre-orthodontic orthognathic surgery (POGS) were compared with patients treated with conventional surgery (CS) with presurgical orthodontics (control) using lateral cephalograms (taken preoperatively, 7 days postoperatively, and 12 months postoperatively). Predictor (group and timing), outcome (cephalometric measurements over time), and other (ie, baseline characteristics) variables were evaluated to determine the differences in postoperative horizontal and vertical positional changes of the mandible, such as point B. Baseline demographics were similar between the groups (N = 37; CS group, n = 17; POGS group, n = 20). The data were analyzed with an independent t test, the Mann-Whitney U test, the Fisher exact t test, Pearson correlation analysis, and simple linear regression analysis. RESULTS: The mean setback of the mandible at point B was similar, but the mandible of the POGS group, particularly the distal segment, moved superiorly during the postoperative period in conjunction with the removal of premature occlusal contacts (P < .001). In the CS group, the mandible had significantly more backward movement 12 months after surgery compared with the POGS group (P < .01). In the POGS group, horizontal and vertical postsurgical changes were linearly correlated with the amount of setback and vertical movement of the mandible. CONCLUSIONS: Mandibular setback surgery using IVRO without presurgical orthodontics leads to considerably different postoperative skeletal and dental changes compared with conventional treatment, with more superior movement being observed at point B during the 1-year postoperative period. PMID- 26259689 TI - A global reference for caesarean section rates (C-Model): a multicountry cross sectional study. AB - OBJECTIVE: To generate a global reference for caesarean section (CS) rates at health facilities. DESIGN: Cross-sectional study. SETTING: Health facilities from 43 countries. POPULATION/SAMPLE: Thirty eight thousand three hundred and twenty four women giving birth from 22 countries for model building and 10,045,875 women giving birth from 43 countries for model testing. METHODS: We hypothesised that mathematical models could determine the relationship between clinical-obstetric characteristics and CS. These models generated probabilities of CS that could be compared with the observed CS rates. We devised a three-step approach to generate the global benchmark of CS rates at health facilities: creation of a multi country reference population, building mathematical models, and testing these models. MAIN OUTCOME MEASURES: Area under the ROC curves, diagnostic odds ratio, expected CS rate, observed CS rate. RESULTS: According to the different versions of the model, areas under the ROC curves suggested a good discriminatory capacity of C-Model, with summary estimates ranging from 0.832 to 0.844. The C-Model was able to generate expected CS rates adjusted for the case-mix of the obstetric population. We have also prepared an e-calculator to facilitate use of C-Model (www.who.int/reproductivehealth/publications/maternal_perinatal_health/c model/en/). CONCLUSIONS: This article describes the development of a global reference for CS rates. Based on maternal characteristics, this tool was able to generate an individualised expected CS rate for health facilities or groups of health facilities. With C-Model, obstetric teams, health system managers, health facilities, health insurance companies, and governments can produce a customised reference CS rate for assessing use (and overuse) of CS. TWEETABLE ABSTRACT: The C-Model provides a customized benchmark for caesarean section rates in health facilities and systems. PMID- 26259692 TI - Are There Clinical or Pathological Parameters of Maxillary Oral Squamous Cell Carcinoma With an Influence on the Occurrence of Neck Node Metastasis? An Appraisal of 92 Patients. AB - PURPOSE: To determine the proportion of patients with cervical metastases caused by maxillary oral squamous cell carcinoma (OSCC) and to identify any clinical or pathologic parameters that might be associated with the occurrence of metastatic neck disease. MATERIALS AND METHODS: A retrospective cohort study of all patients managed with primary surgical resection of maxillary OSCC at the authors' institution from 2006 through 2013 was performed. Cervical lymph node dissection and adjuvant therapy were performed as warranted by preoperative staging examinations or histopathologic evaluation or as recommended after multidisciplinary consultation, and regular follow-up protocols were followed. In this analysis, each maxillary OSCC was assigned to an anterior or a posterior anatomic group based on the location of the primary lesion, with the anatomic tumor location serving as the predictor variable and the occurrence of cervical lymph node metastases as the outcome variable. Descriptive and inferential statistics were calculated with a significance level set at a P value less than .05 and post hoc power analyses were performed. RESULTS: The study sample was composed of 92 patients (38 women, 54 men; average age, 60.9 yr). Overall, 27 patients developed cervical metastases (29.3%). Neck disease was present in 15 patients (16.3%) at initial presentation. Delayed cervical metastases were diagnosed in 12 patients (13%) and manifested after an average period of 11.17 months. The anatomic location of the OSCC within the maxillary structures (anterior vs posterior) and the histologic grade greatly influenced the occurrence of metastatic neck disease. No associations were found for the variables tumor size and resection status. CONCLUSION: In this series, cervical lymph node metastases were frequent and to some degree predictable based on anatomic location and tumor grade. PMID- 26259693 TI - Hand to Hand and Word of Mouth. PMID- 26259694 TI - Acute nicotine treatment attenuates lipopolysaccharide-induced cognitive dysfunction by increasing BDNF expression and inhibiting neuroinflammation in the rat hippocampus. AB - Although nicotine has been shown to improve cognitive function in various studies, the mechanisms underlying acute nicotine treatment-induced neuroprotection remain incompletely understood. In this study, we evaluated the effect of acute nicotine treatment on the cognitive impairment induced by lipopolysaccharide (LPS) and explored the underlying mechanism. We found that acute nicotine injection markedly attenuated LPS-elicited cognitive deficits and suppressed the strong LPS-induced release of IL-1beta, IL-6, and TNF-alpha into serum and the dorsal hippocampus at 4 and 24h after LPS injection. Western blot analysis indicated a clear increase in the levels of cleaved caspase-3 in LPS treated animals but not in nicotine- or saline-treated animals. Furthermore, nicotine administration led to a significant increase in BDNF mRNA expression at 4 and 24h and in BDNF protein expression at 24h after LPS injection in the dorsal hippocampus. Taken together, acute nicotine administration attenuated LPS-induced cognitive dysfunction, and this neuroprotective effect may be related to the up regulation of BDNF and the inhibition of neuroinflammation and apoptosis-related proteins in the dorsal hippocampus. PMID- 26259695 TI - Expression regulation and targeting of the peroxisome proliferator-activated receptor gamma following electrically-induced status epilepticus. AB - The neuroprotective and anti-inflammatory effects of the peroxisome proliferator activated receptor gamma (PPARgamma) agonist rosiglitazone are of particular interest for disease-modifying and antiepileptogenic approaches. We studied the expression of PPARgamma and the impact of rosiglitazone on the consequences of status epilepticus (SE) in a rat post-SE model. Immunohistochemical analysis revealed a selective overexpression of PPARgamma in the piriform cortex of rats with spontaneous seizures. Rosiglitazone administration initiated following SE failed to exert relevant effects on the development of spontaneous seizures and neuronal cell loss. Whereas spatial learning in the Morris water maze was delayed in SE animals with vehicle administration, the learning curve of rosiglitazone treated SE rats showed no significant difference to that of controls. The study provides first evidence arguing against a robust antiepileptogenic effect. However, the findings in the spatial learning paradigm indicate disease-modifying effects. PMID- 26259696 TI - A population management system for improving colorectal cancer screening in a primary care setting. AB - RATIONALE: Provision of colorectal cancer (CRC) screening in primary care is suboptimal; failure to observe screening guidelines poses unnecessary risks to patients and doctors. AIMS AND OBJECTIVES: Implement a population management system for CRC screening; evaluate impact on compliance with evidence-based guidelines. METHODS: DESIGN: A quasi-experimental, prospective quality improvement study design using pre-post-analyses with concurrent controls. SETTING: Six suites within an academic primary care practice. PARTICIPANTS: 5320 adults eligible for CRC screening treated by 70 doctors. INTERVENTION: In three intervention suites, doctors reviewed real-time rosters of patients due for CRC screening and chose practice delegate outreach or default reminder letter. Delegates tracked overdue patients, made outreach calls, facilitated test ordering, obtained records and documented patient deferral, exclusion or decline. In three control suites, doctors followed usual preventive care practices. MAIN OUTCOME MEASURES: CRC screening compliance (including documented decline, deferral or exclusion) and CRC screening completion rates over 5 months. RESULTS: At baseline, there was no significant difference in CRC screening compliance (I: 80.4% and C: 79.6%, P = 0.439) and CRC screening completion rates (I: 78.3% and C: 77.3%, P = 0.398) between intervention and control groups. Post-intervention, compliance rates (I: 88.1% and C: 80.5%, P < 0.01) and completion rates (I: 81.0% and C: 78.1%, P < 0.05) were significantly higher in the intervention group. CONCLUSIONS: A population management system using closed-loop communication may improve CRC screening compliance and completion rates within academic primary care practices. Team-based care using well-designed IT systems can enable sharing of patient care responsibilities and improve patient outcomes. PMID- 26259697 TI - HU-446 and HU-465, Derivatives of the Non-psychoactive Cannabinoid Cannabidiol, Decrease the Activation of Encephalitogenic T Cells. AB - Cannabidiol (CBD), the non-psychoactive cannabinoid, has been previously shown by us to decrease peripheral inflammation and neuroinflammation in mouse experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). Here we have studied the anti-inflammatory effects of newly synthesized derivatives of natural (-)-CBD ((-)-8,9-dihydro-7-hydroxy-CBD; HU-446) and of synthetic (+)-CBD ((+)-8,9-dihydro-7-hydroxy-CBD; HU-465) on activated myelin oligodendrocyte glycoprotein (MOG)35-55-specific mouse encephalitogenic T cells (T(MOG) ) driving EAE/MS-like pathologies. Binding assays followed by molecular modeling revealed that HU-446 has negligible affinity toward the cannabinoid CB1 and CB2 receptors while HU-465 binds to both CB1 and CB2 receptors at the high nanomolar concentrations (Ki = 76.7 +/- 5.8 nm and 12.1 +/- 2.3 nm, respectively). Both, HU-446 and HU-465, at 5 and 10 MUm (but not at 0.1 and 1 MUm), inhibited the MOG35-55-induced proliferation of autoreactive T(MOG) cells via CB1/CB2 receptor independent mechanisms. Moreover, both HU-446 and HU-465, at 5 and 10 MUm, inhibited the release of IL-17, a key autoimmune cytokine, from MOG35-55-stimulated T(MOG) cells. These results suggest that HU-446 and HU-465 have anti-inflammatory potential in inflammatory and autoimmune diseases. PMID- 26259699 TI - Zipf's law holds for phrases, not words. AB - With Zipf's law being originally and most famously observed for word frequency, it is surprisingly limited in its applicability to human language, holding over no more than three to four orders of magnitude before hitting a clear break in scaling. Here, building on the simple observation that phrases of one or more words comprise the most coherent units of meaning in language, we show empirically that Zipf's law for phrases extends over as many as nine orders of rank magnitude. In doing so, we develop a principled and scalable statistical mechanical method of random text partitioning, which opens up a rich frontier of rigorous text analysis via a rank ordering of mixed length phrases. PMID- 26259698 TI - Next-generation analysis of gene expression regulation--comparing the roles of synthesis and degradation. AB - Technological advances now enable routine measurement of mRNA and protein abundances, and estimates of their rates of synthesis and degradation that inform on their values and the degree of change in response to stimuli. Importantly, more and more data on time-series experiments are emerging, e.g. of cells responding to stress, enabling first insights into a new dimension of gene expression regulation - its dynamics and how it allows for very different response signals across genes. This review discusses recently published methods and datasets, their impact on what we now know about the relationships between concentrations and synthesis rates of mRNAs and proteins in yeast and mammalian cells, their evolution, and new hypotheses on translation regulatory mechanisms generated by approaches that involve ribosome footprinting. PMID- 26259700 TI - The relation between CT findings and sputum microbiology studies in active pulmonary tuberculosis. AB - PURPOSE: To evaluate whether CT findings suggesting active pulmonary tuberculosis correlate with sputum microbiological studies, and to determine whether CT could predict infectivity. MATERIALS AND METHODS: Total 108 patients with active pulmonary tuberculosis were enrolled. We reviewed CT findings and sputum microbiological studies. Then, we analyzed the statistical difference in CT findings between the positive and negative groups of each sputum microbiological study (AFB smear, PCR, and culture). Also, we divided the patients into five groups according to sputum AFB smear grade and analyzed linear trends of CT findings between the five groups. RESULTS: Both frequencies and extents of centrilobular micronodules (63% vs 38%, p=0.011 for frequency; 1.6 +/- 1.6 vs 0.6 +/- 1.1, p=0.001 for extent), tree-in-bud opacities (63% vs 33%, p=0.002; 1.6 +/- 1.6 vs 0.5 +/- 0.9, p<0.001, respectively), consolidation (98% vs 81%, p=0.003; 2.7 +/- 1.5 vs 1.3 +/- 1.1, p<0.001, respectively), and cavitation (86% vs 33%, p<0.001; 1.5 +/- 1.2 vs 0.4 +/- 0.7, p<0.001, respectively), were significantly increased in the sputum AFB-positive group than in the negative group. These four CT findings were increase in frequency and extent in the sputum PCR-positive group with or without statistical significance. They did not show significant differences between the sputum culture-positive and negative groups. As the AFB smear grade increased, frequencies and extents of centrilobular micronodules, tree-in-bud, consolidation, and cavitation also increased. CONCLUSION: CT features representing active tuberculosis-centrilobular nodules, tree-in-bud, consolidation, and, cavitation-strongly correlate with the positivity and grading of AFB smear. PMID- 26259701 TI - Acoustic radiation force impulse imaging (ARFI) for differentiation of benign and malignant thyroid nodules--A meta-analysis. AB - OBJECTIVES: Work-up of thyroid nodules remains challenging. Acoustic radiation force impulse imaging (ARFI)-generated shear wave elastography, which can measure quantitatively tissue stiffness (virtual touch tissue quantification) is used as a complement to conventional sonography for improving the diagnosis of thyroid nodules. This meta-analysis was performed to expand on a previous meta-analysis to assess the diagnostic power of ARFI in differentiating benign and malignant thyroid nodules. METHODS: The MEDLINE, PubMed, SpringerLink databases up to December 31, 2014, were searched. The pooled sensitivity, specificity, and summary receiver operating characteristic curve were obtained from individual studies with a random effects model. RESULTS: Sixteen studies that included a total of 2436 nodules in 2147 patients for ARFI studies were analyzed. The overall mean sensitivity and specificity of ARFI for differentiation of thyroid nodules were 0.80 (95% confidence interval [CI], 0.73-0.87) and 0.85 (95% CI, 0.80-0.90), respectively. A significant heterogeneity was found for both sensitivity and specificity of the different studies (P<0.001). The area under the curve for the ARFI was 0.91. CONCLUSIONS: ARFI has high sensitivity and specificity for identification of thyroid. This technique might be useful to select patients with thyroid nodules for surgery. PMID- 26259702 TI - Mitotic redistribution of the mitochondrial network by Miro and Cenp-F. AB - Although chromosome partitioning during mitosis is well studied, the molecular mechanisms that allow proper segregation of cytoplasmic organelles in human cells are poorly understood. Here we show that mitochondria interact with growing microtubule tips and are transported towards the daughter cell periphery at the end of mitosis. This phenomenon is promoted by the direct and cell cycle dependent interaction of the mitochondrial protein Miro and the cytoskeletal associated protein Cenp-F. Cenp-F is recruited to mitochondria by Miro at the time of cytokinesis and associates with microtubule growing tips. Cells devoid of Cenp-F or Miro show decreased spreading of the mitochondrial network as well as cytokinesis-specific defects in mitochondrial transport towards the cell periphery. Thus, Miro and Cenp-F promote anterograde mitochondrial movement and proper mitochondrial distribution in daughter cells. PMID- 26259703 TI - Caught in suffering bodies: a qualitative study of immigrant women on long-term sick leave in Norway. AB - AIMS AND OBJECTIVES: This article explores the issues faced by immigrant women on long-term sick leave due to chronic pain, focusing on their personal perspectives on their daily lives, their bodies and their pain. BACKGROUND: An increasing number of immigrants in Norway present a challenge to the public health service, above all in relation to the health needs of immigrant women, many of whom risk having to take long-term sick leave due to chronic pain. DESIGN: This study has a qualitative design, with participant observation and in-depth interviews. METHODS: Participant observations were carried out from a sample of fourteen immigrant women in an outpatient clinic at a rehabilitation hospital. In addition, qualitative interviews were conducted after the rehabilitation period. A hermeneutic approach was used to understand the meaning of the narrated text. RESULTS: The analysis revealed one main theme, 'Bodies marked by onerous experiences', as well as two subthemes: 'It is in my body' and 'Invisible pain'. The immigrant women struggled with invisible, chronic pain, which they blamed on physically tiring workdays and stressful life situations. Furthermore, they felt that their experiences of discriminative attitudes at the workplace worsened their suffering. CONCLUSIONS: The chronic pain made the immigrant women suffer, because they experienced it as a threatening, incomprehensible and unreal force, without meaning or the ability to be controlled. Their own psychological distress exacerbated their pain. RELEVANCE TO CLINICAL PRACTICE: Immigrant women on long term sick leave are likely to need special approaches that are closely adapted to their different backgrounds and their unique personal experiences. We recommend culturally appropriate family counselling and collaboration with employers at the women's workplaces. PMID- 26259705 TI - Ripened Semihard Cheese Covered with Lard and Dehydrated Rosemary (Rosmarinus officinalis L.) Leaves: Processing, Characterization, and Quality Traits. AB - This study aimed to establish a manufacturing protocol and to characterize semihard cheese covered with lard and rosemary during ripening. After the manufacturing protocol was defined, the cheeses were produced with pasteurized and raw milk from Holstein cows, with and without (control) coating, and then ripened for 60 d. During this period the physicochemical properties, color, proteolysis, texture profile, and sensory acceptance were performed. The early ripening cheeses differed from the others in terms of color and moisture content. Multivariate statistical analysis separated chesses in groups differentiated by the effects of heat treatment of milk and ripening period. The ripened cheeses obtained from raw milk were sensorially more preferred. The coating gave the final products higher moisture content and favored color and texture characteristics. Consumer testing showed that the cheese obtained from raw milk and coated with lard and rosemary was the most preferred (acceptance of 82%) due to the specific coating of rosemary (aroma and flavor). This product has potential to add value and to diversify the production of semihard cheeses. PMID- 26259704 TI - Highly Pathogenic Avian Influenza A(H5N1) Virus Struck Migratory Birds in China in 2015. AB - Approximately 100 migratory birds, including whooper swans and pochards, were found dead in the Sanmenxia Reservoir Area of China during January 2015. The causative agent behind this outbreak was identified as H5N1 highly pathogenic avian influenza virus (HPAIV). Genetic and phylogenetic analyses revealed that this Sanmenxia H5N1 virus was a novel reassortant, possessing a Clade 2.3.2.1c HA gene and a H9N2-derived PB2 gene. Sanmenxia Clade 2.3.2.1c-like H5N1 viruses possess the closest genetic identity to A/Alberta/01/2014 (H5N1), which recently caused a fatal respiratory infection in Canada with signs of meningoencephalitis, a highly unusual symptom with influenza infections in humans. Furthermore, this virus was shown to be highly pathogenic to both birds and mammals, and demonstrate tropism for the nervous system. Due to the geographical location of Sanmenxia, these novel H5N1 viruses also have the potential to be imported to other regions through the migration of wild birds, similar to the H5N1 outbreak amongst migratory birds in Qinghai Lake during 2005. Therefore, further investigation and monitoring is required to prevent this novel reassortant virus from becoming a new threat to public health. PMID- 26259706 TI - Noncontact diffuse correlation tomography of human breast tumor. AB - Our first step to adapt our recently developed noncontact diffuse correlation tomography (ncDCT) system for three-dimensional (3-D) imaging of blood flow distribution in human breast tumors is reported. A commercial 3-D camera was used to obtain breast surface geometry, which was then converted to a solid volume mesh. An ncDCT probe scanned over a region of interest on the mesh surface and the measured boundary data were combined with a finite element framework for 3-D image reconstruction of blood flow distribution. This technique was tested in computer simulations and in vivo human breasts with low-grade carcinoma. Results from computer simulations suggest that relatively high accuracy can be achieved when the entire tumor is within the sensitive region of diffuse light. Image reconstruction with a priori knowledge of the tumor volume and location can significantly improve the accuracy in recovery of tumor blood flow contrasts. In vivo imaging results from two breast carcinomas show higher average blood flow contrasts (5.9- and 10.9-fold) in the tumor regions compared to the surrounding tissues, which are comparable with previous findings using diffuse correlation spectroscopy. The ncDCT system has the potential to image blood flow distributions in soft and vulnerable tissues without distorting tissue hemodynamics PMID- 26259707 TI - Concurrent photoacoustic-ultrasound imaging using single-laser pulses. AB - Conventional ultrasound (US) and photoacoustic (PA) multimodality imaging require the use of a US pulse for US data acquisition and a laser pulse for PA data acquisition. We propose a method for concurrent US and PA data acquisition with a single-laser pulse. A light-absorbing multilayer film that can generate a US pulse based on the thermoelastic effect is used. The selection of appropriate layer thickness, interlayer spacing, and absorption coefficient allows the spectral characteristics of the generated US signal to be adjusted so that it does not overlap with the spectrum of the PA signal generated by the light transmitting through the layer. Thus, the US signal and the PA signal can be generated, received, and separated by using a single-laser pulse combined with spectral filtering. This method is demonstrated using a multilayer film that generates US signals with a center frequency of 24.2 MHz and fractional bandwidth of 26.8%. The synthetic-aperture focusing technique is applied to improve the lateral resolution and the signal-to-noise ratio. A cyst-like phantom and a film phantom were used to demonstrate the feasibility of this method of concurrent PA US imaging using single-laser pulses. PMID- 26259708 TI - The decline in mortality due to acute complications of diabetes mellitus in Brazil, 1991-2010. AB - BACKGROUND: Mortality from acute complications of diabetes, a predominantly preventable condition, although controlled in high income countries, remains a major challenge for low/middle income countries. The aim of this study is to describe trends in mortality from acute complications of diabetes between 1991 and 2010 in Brazil, a period during which a national health system was implemented offering broad access to diabetes treatment. METHODS: We obtained the number of deaths listed in the Brazilian Mortality Information System between 1991 and 2010 as due to acute complications of diabetes (ICD-9 250.1, .2, or .3 and ICD-10 E10-14.0 or 1), corrected this number for ill-defined causes of death and incompleteness in mortality reporting, and calculated mortality rates standardized to the world's population. We describe mortality trends with Joinpoint regressions. RESULTS: Over this 20 year period, mortality due to the acute complications of diabetes fell 70.9 % (95 % CI 67.2 to 74.5 %), from 8.42 (95 % CI 8.27 to 8.57) deaths per 100000 inhabitants in 1991 to 2.45 (95 % CI 2.38 to 2.52) per 100000 in 2010. The reduction occurred in men and women, in all age groups, and in all regions of Brazil. CONCLUSIONS: Mortality from acute complications of diabetes in Brazil has declined markedly in parallel with the implementation of a national health system providing access to insulin and organization of health care. Further decline is possible and necessary. PMID- 26259709 TI - Erratum to: Association study of H2AFZ with schizophrenia in a Japanese case control sample. AB - Table 1 contains several errors as originally published. Table 1 should read as follows; the corrected values are shown in italics. PMID- 26259710 TI - Gluten Introduction, Breastfeeding, and Celiac Disease: Back to the Drawing Board. AB - This commentary by the leadership of the North American Society for the Study of Celiac Disease (NASSCD) concerns recent research findings regarding infant feeding practices. Celiac disease has increased markedly in recent decades, and seroprevalence studies indicate that this is a true rise, rather than one due to increased awareness and testing. Prior studies have suggested that infant feeding practices and timing of initial gluten exposure are central to the development of celiac disease. Two recent multicenter randomized trials tested strategies of early or delayed gluten introduction in infants, and neither strategy appeared to influence celiac disease risk. These studies also found that breastfeeding did not protect against the development of celiac disease. While disappointing, these results should spur the study of wider environmental risk factors beyond infant feeding, such as intrauterine and perinatal exposures as well as environmental influences later in life, including drug exposure, microbial infections, and the microbiome. Given that celiac disease can develop at any age, it is imperative to study these proposed triggers so as to elucidate the loss of tolerance to gluten and to develop future intervention strategies. PMID- 26259712 TI - Biodegradable Polymer Nanogels for Drug/Nucleic Acid Delivery. PMID- 26259711 TI - Long-Term Controlled Protein Release from Poly(Ethylene Glycol) Hydrogels by Modulating Mesh Size and Degradation. AB - Poly(ethylene glycol) (PEG)-based hydrogels are popular biomaterials for protein delivery to guide desirable cellular fates and tissue repair. However, long-term protein release from PEG-based hydrogels remains challenging. Here, we report a PEG-based hydrogel platform for long term protein release, which allows efficient loading of proteins via physical entrapment. Tuning hydrogel degradation led to increase in hydrogel mesh size and gradual release of protein over 60 days of with retained bioactivity. Importantly, this platform does not require the chemical modification of loaded proteins, and may serve as a versatile tool for long-term delivery of a wide range of proteins for drug-delivery and tissue engineering applications. PMID- 26259713 TI - Efficacy assessment of biocides or repellents for the control of Sarcoptes scabiei in the environment. AB - BACKGROUND: Sarcoptes scabiei infection is a contagious disease affecting both humans and animals. The transmission occurs either by direct contact or from the environment where mites could survive several days remaining infective. The number of products available for environmental control of S. scabiei is very limited. The objective of the present study was to assess the efficacy of biocides or repellents against S. scabiei var suis. METHODS: Tested products included pyrethroids: permethrin, esdepallethrin and bioresmethrin, bifenthrin, cypermethrin and imiprothrin, cyfluthrin, tetramethrin and sumithrin. We also tested repellents: DEET, icaridin and IR3535. Sarcoptes scabiei var suis mites were collected from experimentally-infected pigs. For each test, 20 live mites of all motile stages were placed in a plastic Petri dish and sprayed uniformly by each product. Control mites were sprayed by distilled water. The study was performed in triplicate under room conditions and the mites were inspected under a stereomicroscope at intervals (5, 10, 15, 20, 25, 30, 40, 50, 60 min, 2, 3, 4, 5 and 24 h) after exposure to the products. RESULTS: All the products, except the combination of tetramethrin and sumithrin (A-PAR), were able to kill all mites within 24 h. The median survival time was 50 +/- 30.4 min, 120 +/- 309 min, 10 +/ 5.9 min, 40 +/- 36.8 min, 15 +/- 7.3 min, 180 +/- 417 min and 1440 +/- 600 min when mites were exposed to permethrin 4 %, permethrin 0.6%, esdepallethrin and bioresmethrin, bifenthrin, cypermethrin and imiprothrin, cyfluthrin, tetramethrin and sumithrin, respectively. The median survival time was 20 +/- 6.5 min, 15 +/- 4.3 min, 30 +/- 42.1 min and 15 +/- 4.9 min for DEET 25, DEET 50, icaridin 20 and IR3535 20%, respectively. CONCLUSIONS: The results of the present study could support evidence-based use of biocides and repellents in households, hospitals and farms. PMID- 26259715 TI - Polybrominated diphenyl ethers (PBDEs) in herbaceous Centaurium erythraea affected by various sources of environmental pollution. AB - Polybrominated diphenyl ethers (PBDEs) are persistent xenobiotics with harmful effects on humans and wildlife. Their levels in the environment and accumulation in biota must be carefully controlled especially in species harvested from wild populations and commonly used as medicines. Our objective has been to determine PBDE concentrations (BDEs 28, 47, 66, 85, 99, 100, 153, 154, 183 and 209) in Centaurium erythraea collected at sites with various levels of environmental pollution. PBDE congener profiles in C. erythraea were dominated by BDE209, which accounted for 47-89% of the total PBDE burden in the plants. Principal Component and Classification Analysis, which classifies the concentration of PBDEs in C. erythraea, allowed us to distinguish the pattern of these compounds characteristic for the origin of pollution: BDEs 28, 47, 66, 85, 99, 100 for lignite and general chemical industry and the vicinity of an expressway and BDEs 183 and 209 for a thermal power plant and ferrochrome smelting industry. Careful selection of sites with C. erythraea for medicinal purposes is necessary as this herb can accumulate PBDEs while growing at polluted sites. PMID- 26259714 TI - Inhibition of DPP-4 reduces acute mortality after myocardial infarction with restoration of autophagic response in type 2 diabetic rats. AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) worsens the outcome after myocardial infarction (MI). Here, we hypothesized that inhibition of dipeptidyl peptidase-4 (DPP-4) improves survival after MI in T2DM by modifying autophagy in the non infarcted region of the heart. METHODS AND RESULTS: Under baseline conditions, there was no significant difference between levels of myocardial autophagy marker proteins in OLETF, a rat model of T2DM, and in LETO, a non-diabetic control. However, in contrast to the response in LETO, LC3-II protein and LC3-positive autophagosomes in the non-infarcted region of the myocardium were not increased after MI in OLETF. The altered autophagic response in OLETF was associated with lack of AMPK/ULK-1 activation, attenuated response of Akt/mTOR/S6 signaling and increased Beclin-1-Bcl-2 interaction after MI. Treatment with vildagliptin (10 mg/kg/day s.c.), a DPP-4 inhibitor, suppressed Beclin-1-Bcl-2 interaction and increased both LC3-II protein level and autophagosomes in the non-infarcted region in OLETF, though it did not normalize AMPK/ULK-1 or mTOR/S6 signaling. Plasma insulin level, but not glucose level, was significantly reduced by vildagliptin at the dose used in this study. Survival rate at 48 h after MI was significantly lower in OLETF than in LETO (32 vs. 82%), despite similar infarct sizes. Vildagliptin improved the survival rate in OLETF to 80%, the benefit of which was abrogated by chloroquine, an autophagy inhibitor. CONCLUSIONS: The results indicate that vildagliptin reduces T2DM-induced increase in post-MI acute mortality possibly by restoring the autophagic response through attenuation of Bcl-2-Beclin-1 interaction. PMID- 26259716 TI - Mechanistic understanding of the nonlinear pharmacokinetics and intersubject variability of simeprevir: A PBPK-guided drug development approach. AB - Simeprevir, a hepatitis C virus (HCV) NS3/4A protease inhibitor, displays nonlinear pharmacokinetics (PK) at therapeutic doses. Using physiologically based PK modeling, various drug-drug interactions were simulated with simeprevir as victim drug to identify whether saturation of the predominant metabolic enzyme (CYP3A4) or the active hepatic transporters (organic anion-transporting polypeptide (OATP)1B1/3) could account for the nonlinear PK. Interactions with ritonavir, a strong CYP3A4 inhibitor that does not affect OATP (at 100 mg dose), erythromycin, a moderate CYP3A4 inhibitor, and efavirenz, a moderate CYP3A inducer that does not affect OATP, demonstrated the involvement of CYP3A4. Interaction studies with low-dose cyclosporine confirmed the role of OATP. The interplay between hepatic uptake and CYP3A4 metabolism was verified by simulations with rifampicin, a potent CYP3A4 inducer and OATP1B1/3 inhibitor, and maintenance doses of cyclosporine. Saturation of gut and liver metabolism by CYP3A4, and saturation of hepatic uptake by OATP1B1/3, seem to account for the observed nonlinear PK of simeprevir. PMID- 26259717 TI - Separation of Mycobacterium abscessus into subspecies or genotype level by direct application of peptide nucleic acid multi-probe- real-time PCR method into sputa samples. AB - BACKGROUND: Recently, we introduced a novel peptide nucleic acid (PNA) multi probe real time PCR method targeting the hsp65 gene (hsp65 PNA RT-PCR) to distinguish Mycobacterium abscessus groups. METHODS: Here, we evaluated the usefulness of the hsp65 PNA RT-PCR for the direct identification of the M. abscessus group at the subspecies and genotype levels from sputa samples. The method was applied to total sputa DNA from 60 different patients who were identified as having mycobacterial infections via rpoB PCR restriction analysis of the same cultures. RESULTS: The hsp65 PNA RT-PCR method had higher sensitivity than the multi-probe real-time PCR assay targeting hsp65 (HMPRT-PCR) for the detection of M. abscessus from sputum [96.7 % (29/30 samples) vs. 70 % (21/30 samples); 100 % specificity]. CONCLUSIONS: These results suggest that the PNA based method is feasible for the detection of M. abscessus members not only from cultures but also directly from sputa. PMID- 26259718 TI - The Edible Red Alga Porphyra yezoensis Promotes Neuronal Survival and Cytoarchitecture in Primary Hippocampal Neurons. AB - The edible red alga Porphyra yezoensis is among the most popular marine algae and is of economic and medicinal importance. In the present study, the neurotrophic and neuroprotective activities of the ethanol extract of P. yezoensis (PYE) were investigated in primary cultures of hippocampal neurons. Results revealed that PYE significantly increased neurite outgrowth at an optimal concentration of 15 ug/mL. PYE dose-dependently increased viable cells, significantly accelerated the rate of neuronal differentiation in cultures, promoted axodendritic arborization, and eventually induced synaptogenesis. In addition to morphological development, PYE also promoted functional maturation as indicated by the staining of live cultures with FM 1-43. Moreover, PYE increased neuronal survivability, which was attributed to reduced apoptosis and its ROS scavenging activity. Taurine, a major organic acid in PYE (2.584/100 mg of dry PYE) promoted neurite outgrowth in a dose-dependent manner, and this promotion was suppressed by the taurine antagonist isethionic acid. The study indicates that PYE and its active component, taurine, facilitate neuronal development and maturation and have a neuroprotective effect. PMID- 26259719 TI - Betaine alleviates hepatic lipid accumulation via enhancing hepatic lipid export and fatty acid oxidation in rats fed with a high-fat diet--CORRIGENDUM. AB - In the abstract, these sentences (page 1, line 5) should be: 'Additionally, hepatic betaine-homocysteine methyltransferase concentration as well as its mRNA abundance and lecithin level were found increased (P < 0. 05) by betaine supplementation in both basal diet-fed rats and high-fat diet-fed rats. Betaine administration in high-fat diet-fed rats exhibited a higher (P < 0.05) concentration of hepatic carnitine palmitoyltransferase 1 (CPT1) compared with high-fat diet-fed rats.' PMID- 26259720 TI - Bioengineering for Organ Transplantation: Progress and Challenges. AB - Organ transplantation can offer a curative option for patients with end stage organ failure. Unfortunately the treatment is severely limited by the availability of donor organs. Organ bioengineering could provide a solution to the worldwide critical organ shortage. The majority of protocols to date have employed the use of decellularization-recellularization technology of naturally occurring tissues and organs with promising results in heart, lung, liver, pancreas, intestine and kidney engineering. Successful decellularization has provided researchers with suitable scaffolds to attempt cell reseeding. Future work will need to focus on the optimization of organ specific recellularization techniques before organ bioengineering can become clinically translatable. This review will examine the current progress in organ bioengineering and highlight future challenges in the field. PMID- 26259722 TI - Application of Foam-gel Technique to Control CO Exposure Generated During Spontaneous Combustion of Coal in Coal Mines. AB - In China, 47.3% of state-owned coal mines are located in coal seams that are prone to spontaneous combustion. The spontaneous combustion of coal is the main cause of the generation of a large amount of carbon monoxide, which can cause serious health issues to miners. A new technique using foam-gel formation was developed to effectively control the spontaneous combustion of coal. The gel can capture more than 90% of the water in the grout and at the same time the foam can cover dangerous areas in the goaf by stacking and cooling of foam in all directions. In this study, a mechanism of foam-gel formation was introduced and the optimal proportions of additives were defined based on experiments of different foaming properties, gelling time and water loss rate as the main index parameters. The results of a field application in a coal mine promise that this new technique would effectively prevent coal oxidation in the goaf and reduce the generation of carbon monoxide. PMID- 26259721 TI - Modelling of drug-induced QT-interval prolongation: estimation approaches and translational opportunities. AB - Safety pharmacology studies are performed to assess whether compounds may provoke severe arrhythmias (e.g. Torsades de Pointes, TdP) and sudden death in man. Although there is strong evidence that drugs inducing TdP in man prolong the QT interval in vivo and block the human ether-a-go-go-related gene (hERG) ion channel in vitro, not all drugs affecting the QT interval or the hERG will induce TdP. Nevertheless, QT-interval prolongation and hERG blockade currently represent the most accepted early risk biomarkers to deselect drugs. An extensive pharmacokinetic/pharmacodynamic (PK/PD) analysis is developed to understand moxifloxacin's-induced effects on the QT interval by comparing the relationship between results of an in vitro patch-clamp model to in vivo models. The frequentist and the fully Bayesian estimation procedures were compared and provided similar performances when the best model selected in NONMEM is subsequently implemented in WinBUGS, which guarantees a straightforward calculation of the probability of QT-interval prolongation greater than 2.5 % (10 ms). The use of the percent threshold to account for the intrinsic differences between species and a new calculation of the probability curve are introduced. The concentration providing the 50 % probability indicates that dogs are more sensitive than humans to QT-interval prolongation. However, based on the drug effect, a clear distinction between species cannot be made. An operational PK/PD model of agonism was used to investigate the relationship between effects on the hERG and QT-interval prolongation in dogs. The proposed analysis contributes to establish a translational relationship that could potentially reduce the need for thorough QT studies. PMID- 26259724 TI - Anakoinosis: Communicative Reprogramming of Tumor Systems - for Rescuing from Chemorefractory Neoplasia. AB - Disruptive technologies, such as communicative reprogramming (anakoinosis) with cellular therapies in situ for treating refractory metastatic cancer allow patient care to accelerate along a totally new trajectory and highlight what may well become the next sea change in the care of patients with many types of advanced neoplasia. Cellular therapy in situ consisted of repurposed drugs, pioglitazone plus all-trans retinoic acid or dexamethasone or interferon-alpha (dual transcriptional modulation) combined with metronomic low-dose chemotherapy or low-dose 5-azacytidine, plus/minus classic targeted therapy. The novel therapeutic tools for specifically designing communication processes within tumor diseases focus on redirecting (1) rationalizations of cancer hallmarks (constitution of single cancer hallmarks), (2) modular events, (3) the 'metabolism' of evolutionary processes (the sum of therapeutically and intrinsically inducible evolutionary processes) and (4) the holistic communicative context, which determines validity and denotation of tumor promoting communication lines. Published data on cellular therapies in situ (6 histologic tumor types, 144 patients, age 0.9-83 years) in castration-resistant prostate cancer, pretreated renal clear cell carcinoma, chemorefractory acute myelocytic leukemia, multiple myeloma > second-line, chemorefractory Hodgkin lymphoma or multivisceral Langerhans cell histiocytosis, outline the possibility for treating refractory metastatic cancer with the hope that this type of reprogrammed communication will be scalable with minimal toxicity. Accessibility to anakoinosis is a tumor inherent feature, and cellular therapy in situ addresses extrinsic and intrinsic drug resistance, by redirecting convergent organized communication tools, while been supported by quite different pattern of (molecular-)genetic aberrations. PMID- 26259725 TI - Effect of levofloxacin treatment on semen hyperviscosity in chronic bacterial prostatitis patients. AB - Changes in seminal fluid viscosity (SFV), reactive oxygen species (ROS) production, cytokines and seminal leucocyte concentration related to microbiological outcome in patients with chronic bacterial prostatitis (CBP) were studied. One hundred and ten infertile patients with CBP (positive sperm culture >=10(5) colony-forming units [CFU] ml(-1), pathogens or Chlamydia in expressed prostatic secretions) were treated with levofloxacin 500 mg daily for 14 consecutive days per month for 3 months. In case of bacterial prostatitis, two conditions were examined: responders, eradication of 0 to <10(3) CFU ml(-1) (n = 78) and poor responders, >10(3) to <10(5) CFU ml(-1) (n = 32). Compared with poor responders, responders showed a significant increase of sperm progressive motility and a significant decrease in seminal leucocyte count, SFV, liquefaction time, ROS production (in all fractions and conditions), seminal tumour necrosis factor-alpha and interleukin 6. None of these variables showed significant differences compared with a control group of 37 fertile men. On the other hand, the poor responders showed significant changes in these variables compared with matched pretreatment values. In patients with CBP, antibiotic therapy alone leads to eradication in ~71%, with improvement of sperm progressive motility, SFV and the framework of prooxidative factors. However, in the remaining ~29% with poor antibiotic responsiveness, a deterioration of all variables is observed. PMID- 26259726 TI - Influence of healing time on the mechanical properties of an implanted mesh. PMID- 26259727 TI - The effects of acoustical refurbishment of classrooms on teachers' perceived noise exposure and noise-related health symptoms. AB - OBJECTIVES: To investigate whether acoustical refurbishment of classrooms for elementary and lower secondary grade pupils affected teachers' perceived noise exposure during teaching and noise-related health symptoms. METHODS: Two schools (A and B) with a total of 102 teachers were subjected to an acoustical intervention. Accordingly, 36 classrooms (20 and 16 in school A and school B, respectively) were acoustically refurbished and 31 classrooms (16 and 15 in school A and school B, respectively) were not changed. Thirteen classrooms in school A were interim "sham" refurbished. Control measurements of RT and activity sound levels were measured before and after refurbishment. Data on perceived noise exposure, disturbance attributed to different noise sources, voice symptoms, and fatigue after work were collected over a year in a total of six consecutive questionnaires. RESULTS: Refurbished classrooms were associated with lower perceived noise exposure and lower ratings of disturbance attributed to noise from equipment in the class compared with unrefurbished classrooms. No associations between the classroom refurbishment and health symptoms were observed. Before acoustical refurbishment, the mean classroom reverberation time was 0.68 (school A) and 0.57 (school B) and 0.55 s in sham refurbished classrooms. After refurbishment, the RT was approximately 0.4 s in both schools. Activity sound level measurements confirmed that the intervention had reduced the equivalent sound levels during lessons with circa 2 dB(A) in both schools. CONCLUSION: The acoustical refurbishment was associated with a reduction in classroom reverberation time and activity sound levels in both schools. The acoustical refurbishment was associated with a reduction in the teachers' perceived noise exposure, and reports of disturbance from equipment in the classroom decreased. There was no significant effect of the refurbishment on the teachers' voice symptoms or fatigue after work. PMID- 26259728 TI - General practitioners' and occupational health physicians' views on their cooperation: a cross-sectional postal survey. AB - PURPOSE: Prevention, rehabilitation and reintegration into the workplace are examples of overlapping work fields of general practitioners (GPs) and occupational health physicians (OPs). In Germany, however, cooperation between GPs and OPs is often lacking or suboptimal. In this article, we present GPs' and OPs' views on a variety of aspects of their cooperation and differences between them. METHODS: Survey questionnaire was developed on the basis of literature research and results of focus group interviews. Cross-sectional postal survey among GPs (n = 1000) and OPs (n = 383) was performed in the federal state of Baden-Wurttemberg, Germany. Explorative descriptive and logistic regression analyses were carried out (controlling for potential confounders). RESULTS: Response rates were 31 and 48 %, respectively. Mutual telephone calls were the most frequent contact medium (49 and 91 %, respectively). Both groups considered themselves to have clearly separate areas of responsibility (median = 4, rating scale from 1 "agree not at all" to 5 "agree definitely"). Necessity to cooperate and need to improve cooperation were both rated as 4 (by GPs) and 5 (by OPs), respectively (p < 0.001, Wilcoxon test). Several variables were found to be different by logistic regression analysis of answers from the two groups (e.g. in regard to importance of rehabilitation, primary prevention services, caring for chronically ill workers or changing of workplace conditions). Sensitive topics (e.g. concerning mutual rivalry, remuneration or adherence to medical confidentiality) were also found to be rated differently. CONCLUSION: The data show potential interest of both physicians groups to develop cooperation. As the ratings often differed significantly, particularly in regard to statements presented, answers influenced by social desirability are generally unlikely. PMID- 26259730 TI - Effect of M-phase kinase phosphorylations on type 1 inositol 1,4,5-trisphosphate receptor-mediated Ca2+ responses in mouse eggs. AB - The type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) mediates increases in the intracellular concentration of Ca(2+) ([Ca(2+)]i) during fertilization in mammalian eggs. The activity of IP3R1 is enhanced during oocyte maturation, and phosphorylations by M-phase kinases are thought to positively regulate the activity of IP3R1. Accordingly, we and others have found that IP3R1 is phosphorylated at S(421), T(799) (by Cdk1) and at S(436) (by ERK). Nevertheless, the effects of these phosphorylations on the function of the receptor and their impact on [Ca(2+)]i oscillations in eggs have not been clearly examined. To address this, we expressed in mouse oocytes an IP3R1 variant with the three indicated phosphorylation sites replaced by acidic residues, IIIE-IP3R1, such that it would act like a constitutively phosphorylated IP3R1, and examined [Ca(2+)]i parameters in response to stimuli. We found that overexpression of wild type (wt-IP3R1) or IIIE-IP3R1 in oocytes containing endogenous receptors caused dominant negative-like effects on Ca(2+) release and oscillations. Therefore, we first selectively removed the endogenous IP3R1, and subsequently expressed the exogenous receptors. We found that in response to injection of PLCzeta cRNA, eggs without endogenous IP3R1 failed to mount persistent Ca(2+) oscillations, although expression of wt-IP3R1 restored their [Ca(2+)]i oscillatory activity. We also observed that the Ca(2+) oscillatory ability and the sensitivity to IP3 in eggs expressing IIIE-IP3R1 were greater than in those expressing wt-IP3R1. Lastly, we found that exogenous IP3R1s are resistant to downregulation and support longer oscillations and of higher amplitude. Altogether, our results show that phosphorylations by Cdk1 and MAPK enhance the activity of IP3R1, which is consistent with its maximal activity observed at the time of fertilization and the role of Ca(2+) release in egg activation. PMID- 26259731 TI - Progression of coronary artery calcification by cardiac computed tomography. AB - The presence and extent of coronary artery calcification (CAC) is established in primary prevention since the CAC score is the single best predictor of future cardiovascular events. While CAC progresses with increasing age, individual CAC progression can be estimated based on the subject's age, gender, and CAC percentile at first examination. To date, several algorithms and methods for the definition of CAC progression are available in the literature. Increased CAC progression is associated with traditional cardiovascular risk factors including hypertension, diabetes, and smoking status. Also, lipid-lowering therapy may influence the progression of CAC. Epicardial adipose tissue is a further cardiovascular risk marker that may lead to intensified CAC progression if its volume increases. In terms of clinical implications, initial data suggest that extensive CAC progression is linked to worse outcome; however, further studies are needed to establish this relationship and to define appropriate time intervals between repetitive examinations. This review article gives an overview of the existing literature with an emphasis on various definitions of CAC progression, predictors of increased CAC progression, as well as clinical implications. PMID- 26259732 TI - OCT demonstrating neoatherosclerosis as part of the continuous process of coronary artery disease. AB - Although the advent of drug-eluting stents has reduced the rates of target vessel revascularization, there are observations of ongoing stent failure occurring very late after stent implantation and presenting as very late restenosis or as very late stent thrombosis. The de novo development of atherosclerosis within the neointimal region, called neoatherosclerosis, has been identified as one of the pathomechanisms of these observed late stent failures. The mechanisms of neoatherosclerosis development and its association with stent failure are currently the subject of intensive research. Optical coherence tomography (OCT) is an invasive imaging modality that allows us to visualize the micromorphology of coronary arteries with near-histological resolution, thus providing detailed assessment of the morphological characteristics of the neointima after stent implantation, including neoatherosclerosis. Several OCT studies have tried to provide in vivo insights in the mechanisms of neoatherosclerosis development and its association with late stent failure. This review summarizes the current insights into neoatherosclerosis obtained with OCT and discusses the association of neoatherosclerosis with late stent failure. PMID- 26259733 TI - Progression of coronary artery disease. Experience with computed tomography. AB - Coronary artery disease (CAD) begins with asymptomatic atherosclerotic changes in the vessel wall. Gradual or abrupt progression of some of these early lesions eventually leads to symptomatic luminal narrowing. Coronary computed tomography angiography (CTA) allows for a minimally invasive assessment of these wall changes and of the severity of luminal narrowing, and is thus an attractive method for assessing progression/regression. However, because of the associated radiation exposure and concern about false-positive findings, CTA is not recommended as a clinical screening test. Owing to the significantly lower spatial resolution compared with invasive modalities, its application as a tool for clinical progression/regression trials is limited. Therefore, while there are extensive data from both CT coronary artery calcium scoring and CTA studies demonstrating the prognostic value of luminal stenosis as well as the extent and characteristics of plaque, data describing progression/regression are limited. PMID- 26259735 TI - Methods of a national survey of young Aboriginal and Torres Strait Islander people regarding sexually transmissible infections and bloodborne viruses. AB - OBJECTIVE: To describe the methods and basic demographics of participants in a national survey of Aboriginal and Torres Strait Islander (Aboriginal) people specific to sexually transmissible infections and bloodborne viruses. METHODS: A national cross-sectional survey of Aboriginal people aged 16-29 years in all Australian jurisdictions between 2011 and 2013 conducted at Aboriginal community events. Questions comprised demographic information, knowledge, risk behaviours and health service utilisation. Questionnaires were completed on personal digital assistants (PDAs). RESULTS: A total of 2,877 people at 21 unique community events completed the questionnaire. A total of 59% of participants were female, median age was 21 years and more than 60% were single at the time of the survey. Just over half the participants were resident in an urban area (53%) and 38% were from a regional area. Aboriginal health organisations played an important role in implementing the research. PDAs were found to be an acceptable method for collecting health information. CONCLUSION: This survey has recruited a large representative sample of Aboriginal people aged 16-29 years using a methodology that is feasible, acceptable and repeatable. IMPLICATIONS: The methodology provides a model for ongoing monitoring of this population as programs and policies are implemented to address young Aboriginal people's STI and BBV risks. PMID- 26259736 TI - Exploring vaginal ring acceptability for contraception and sexually transmissible infection protection in India: a qualitative research study. AB - Background New vaginal rings are being developed as single and multipurpose prevention technologies to protect women from pregnancy and/or sexually transmissible infections, such as HIV. Data on ring acceptability in low-resource settings is critical for new technologies to meet user needs. METHODS: Women from slum and lower-income areas around Delhi, India, participated in focus group discussions on vaginal ring product perceptions and preferences. Participants were recruited based on following eligibility categories: age, marital status, contraceptive use, and number of children. The translated transcriptions of the qualitative data were analysed using a coding scheme generated from the areas of inquiry and relevant literature. RESULTS: A total of 103 women from lower-middle class or slum areas in Delhi participated in 13 focus group discussions between December 2012 and January 2013. Participants shared perceptions of vaginal ring product attributes, including size, colour, intended use (single indication or dual purpose), duration of use, side effects, biodegradability, and various preferences regarding product use, including access, use during sex, wear patterns, cleaning, and disposal. Participants also reflected on willingness to pay and male partner acceptability. CONCLUSIONS: The results of this hypothetical acceptability study indicate that these low-income women in Delhi are: willing to try vaginal rings; unconcerned about wearing them during sex; very interested in protection from infections and unintended pregnancy; indifferent about colour of new rings; emphatic about being told that rings may change colour from menstrual blood staining; comfortable with thinner rings; willing to try thicker rings once familiar with thinner rings; in favour of starting with 1-month rings and then transitioning to longer-term rings; and in favour of first accessing rings at a facility and then managing resupply independently. PMID- 26259734 TI - Regulation of human glia by multiple sclerosis disease modifying therapies. AB - This review focuses on the effects of the agents currently approved (or in late clinical trials) as therapies for multiple sclerosis (MS) on the glial cell populations of the central nervous system (CNS). These are comprised of astrocytes, microglia, and oligodendrocytes (OLs), and their progenitors (OPCs). Although the efficacy of these agents is to date established only for the relapsing component of the disease and linked to effects on the systemic immune system, each has been examined with regard to effects on the CNS compartment. The impact of therapies on glia would include modulating these cells immune reactivity, which is considered to underlie the tissue injury process in MS and to any subsequent repair process. As reviewed, these agents can exert their effects either indirectly by modulating the constituents of the systemic immune system or directly depending on their capacity to traverse the blood brain barrier (BBB). Most available data has been derived from administration of these agents in animal models or application to glial cells in vitro. The challenge remains of translating these observations into effective means to impact on the progressive course of disease and reverse existent disabilities. PMID- 26259737 TI - [Routine hormonal therapy in the heart transplant donor]. AB - BACKGROUND: Successful heart transplantation depends largely on donor heart function. During brain death many hormonal changes occur. These events lead to the deterioration of the donor hearts. The 2002 Crystal Consensus advises the use of a triple hormonal scheme to rescue marginal cardiac organs. MATERIAL AND METHODS: A prospective, longitudinal study was conducted on potential donor hearts during the period 1 July 2011 to 31 May 2013. All donor hearts received a dual hormonal rescue scheme, with methylprednisolone 15mg/kg IV and 200mcg levothyroxine by the enteral route. There was at least a 4 hour wait prior to the harvesting. The preload and afterload was optimised. The variables measured were: left ventricular ejection fraction cardiac graft recipient; immediate and delayed mortality. RESULTS: A total of 30 orthotopic heart transplants were performed, 11 female and 19 male patients, with age range between 19 and 63 years-old (Mean: 44.3, SD 12.92 years). The donor hearts were 7 female and 23 male, with age range between 15 and 45 years-old (mean 22.5, SD 7.3 years). Immediate mortality was 3.3%, 3.3% intermediate, and delayed 3.3%, with total 30 day-mortality of 10%. Month survival was 90%. The immediate graft left ventricular ejection fraction was 45%, 60% intermediate, and 68% delayed. The causes of death were: 1 primary graft dysfunction, one massive pulmonary embolism, and one due to nosocomial pneumonia. CONCLUSION: It was concluded that the use of double rescue scheme hormonal therapy is useful for the recovery and preservation of the donor hearts. This scheme improves survival within the first 30 days after transplantation. PMID- 26259738 TI - [Marjolin's ulcer. A 10 year experience in a diabetic foot unit]. AB - BACKGROUND: Marjolin's ulcer is defined as the appearance of a neoplasm within a chronic wound. The most common histological type is squamous. A total of 2 cases treated in our hospital are presented. CLINICAL CASE: Case 1. A 71 year old man who presented with redness and suppuration from the wounds he had in his right foot after an electric shock 40 years earlier. The radiology showed involvement of the 4 degrees and 5 degrees metatarsal. Supracondylar amputation was performed, showing a well-differentiated invasive squamous cell carcinoma. CASE 2: A 56 year old male, paraplegic for 20 years. He was treated due to an infected right heel ulcer, with partial improvement, but the ulcers persisted. Biopsy was performed, reporting as epidermoid carcinoma. Infracondylar amputation was performed. The diagnosis was a well-differentiated squamous cell carcinoma infiltrating the dermis. CONCLUSION: The prevalence of Marjolin's ulcer is 1.3 2.2% of all ulcers. Diagnosis is difficult, so biopsy is recommended on any suspicious lesion or ulcer that has received conservative treatment for one month without improvement, although this time limit is not clear. The treatment is the surgery. Local excision with a margin of an inch is enough. If the ulcer is extensive, amputation is required. Survival is estimated between 66 and 80% at 2 years, with recurrence rates of 23%. Unfavourable factors are poor tumour differentiation and metastasis, appearing in 20% of cases. PMID- 26259739 TI - [Skills comparison using a 2D vs. 3D laparoscopic simulator]. AB - BACKGROUND: The development and application of 3D images in laparoscopic surgery has brought the benefit of in-depth perception that traditional laparoscopic surgery lacked. Previous studies in surgical populations have demonstrated the advantages of 3D technology. To limit bias of the previous experiences of participants, this study was performed in a population without any experience in this area. MATERIAL AND METHODS: An experimental, open, cross-sectional, comparative study between surgical skills achievements using 2D and a 3D laparoscopy equipment, using each subject as their own control. Six skills were evaluated in 2D and 3D modalities. RESULTS: Of the 40 participants included, 20 began the skills in the 2D modality and then performed them in 3D, and the other 20 began in 3D. Of the 118 skills evaluated there was a time improvement in 72% in the 3D group compared to 37% in the 2D modality (P=.000). The accomplishment percentage using the 3D laparoscopy was greater for both groups. There was a statistically significant difference in the better time for the 3D performed tasks. Just over half (52.5%) of participants preferred 3D laparoscopy, 15% preferred 2D, and 32.5% had no preferences. DISCUSSION: As other studies have demonstrated, there was improvement in the overall performance using the 3D laparoscope. Bias was limited by using a population without surgical experience. CONCLUSIONS: 3D laparoscopic surgical skills showed superior to 2D, with higher percentages of tasks completion, less time in performing them, and a shorter learning curve. PMID- 26259740 TI - [Ventriculo-gallbladder shunt: An alternative for the treatment of hydrocephalus]. AB - BACKGROUND: In the management of hydrocephalus, the ventriculo-gallbladder shunt is justified in situations where the ventriculo-peritoneal shunt is not useful due to peritoneal involvement and/or when the ventriculo-auricular and ventriculo pleural shunts are contraindicated. CLINICAL CASE: A 27 year-old female with hydrocephalus at birth, managed with ventricle-peritoneal shunt, modified 3 times throughout her life due to repeated infections and other different reasons. She was admitted due to colitis caused by Clostridium difficile, presenting concomitant signs of intracranial hypertension and neurological impairment. This led to a review and change of the ventriculo-peritoneal shunt system, with distal dysfunction due to peritoneal thickening. Atrial and pleural shunts were not indicated because the risk of infection. As an alternative, it was decided to place the distal end of the catheter in the gallbladder. The patient recovered her neurological functions after the surgery. CONCLUSIONS: Drainage alternatives may be needed in 5% of patients with valvular shunt dysfunction. The ventriculo gallbladder is a good and viable option because it has an absorptive capacity of 1500cc liquid daily, besides being an excellent drainage through the bile duct. The abdominal surgery is easy to perform, and it is an alternative option in the failure of the ventriculo-peritoneal shunt. PMID- 26259741 TI - [Skin and tissue bank: Operational model for the recovery and preservation of tissues and skin allografts]. AB - Tissue storage is a medical process that is in the regulation and homogenisation phase in the scientific world. The international standards require the need to ensure safety and efficacy of human allografts such as skin and other tissues. The activities of skin and tissues banks currently involve their recovery, processing, storage and distribution, which are positively correlated with technological and scientific advances present in current biomedical sciences. A description is presented of the operational model of Skin and Tissue Bank at INR as successful case for procurement, recovery and preservation of skin and tissues for therapeutic uses, with high safety and biological quality. The essential and standard guidelines are presented as keystones for a tissue recovery program based on scientific evidence, and within an ethical and legal framework, as well as to propose a model for complete overview of the donation of tissues and organ programs in Mexico. Finally, it concludes with essential proposals for improving the efficacy of transplantation of organs and tissue programs. PMID- 26259742 TI - [Risk factors for nosocomial pneumonia in patients with abdominal surgery]. AB - BACKGROUND: The risk of post-operative pneumonia is a latent complication. A study was conducted to determine its risk factors in abdominal surgery. MATERIAL AND METHODS: A cross-sectional study was performed that included analysing the variables of age and gender, chronic obstructive pulmonary disease and smoking, serum albumin, type of surgery and anaesthesia, emergency or elective surgery, incision site, duration of surgery, length of hospital stay, length of stay in the intensive care unit, and time on mechanical ventilation. The adjusted odds ratio for risk factors was obtained using multivariate logistic regression. RESULTS: The study included 91 (9.6%) patients with pneumonia and 851 (90.4%) without pneumonia. Age 60 years or over (OR=2.34), smoking (OR=9.48), chronic obstructive pulmonary disease (OR=3.52), emergency surgery (OR=2.48), general anaesthesia (OR=3.18), surgical time 120 minutes or over (OR=5.79), time in intensive care unit 7 days or over (OR=1.23), time on mechanical ventilation greater than or equal to 4 days (OR=5.93) and length of post-operative hospital stay of 15 days or over (OR=1.20), were observed as independent predictors for the development of postoperative pneumonia. CONCLUSIONS: Identifying risk factors for post-operative pneumonia may prevent their occurrence. The length in the intensive care unit of greater than or equal to 7 days (OR=1.23; 95% CI 1.07 - 1.42) and a length postoperative hospital stay of 15 days or more (OR=1.20; 95% CI 1.07 - 1.34) were the predictive factors most strongly associated with lung infection in this study. PMID- 26259743 TI - [Cervical lymphangioma in the adult. A report of 2 cases]. AB - BACKGROUND: Cervical lymphangiomas are uncommon benign congenital malformations usually present in children, and are rare in adults. Currently, complete resection is still the standard care. Two cases are presented of a cervical lymphangioma in an adult. The diagnosis and surgical approach is also discussed. CLINICAL CASE: Case 1. The first case is a 23 year old male with chief complaint of a tumour in the posterior triangle of the neck, which showed a substantial increase in size in the last 9 months. No associated signs or symptoms, or any trauma history was reported. CT scan of the neck showed images suggestive of a posterior cervical lymphangioma. Exploratory cervical surgery was performed, with complete resection of a cystic tumour located in the posterior triangle of the neck. Surgery was performed without complications and postoperative care was unremarkable. CASE 2: The second case is a 28 woman with a cystic tumour in submandibular space. She had history of a previous incomplete operation in another institution 2 years ago, with recurrence of the tumour. A second surgery was performed with complete resection without complications, and with a good outcome. CONCLUSIONS: Cervical lymphangioma is a very rare benign disease, surgical treatment is preferred, but sclerotherapy can be used as alternative treatment. PMID- 26259744 TI - [Clinical features of strabismus in psychomotor retardation]. AB - BACKGROUND: In psychomotor retardation there is an abnormal development of mental, sensory and motor skills associated with ocular manifestations. There are biological and psychosocial risk factors that predispose an individual to neurological damage. From 50% to 80% of patients with strabismus retardation have special features that differentiate it from the rest of strabismus in healthy patients. OBJECTIVE: To determine the most common type of strabismus in patients with psychomotor retardation and their clinical features. MATERIAL AND METHODS: Patients with psychomotor retardation and strabismus were included. An ophthalmological examination was performed, as well as an evaluation of the characteristics of strabismus, including perinatal and post-natal history. RESULTS: Esotropia was the most frequent squint with 65.3%, followed by exotropia with 32.7%. The variability in the squint magnitude was 60% in both types, and 6 patients had dissociated vertical deviation. Most of the patients started to present strabismus since they were born. The most frequent perinatal risk factors were threatened miscarriage, pre-eclampsia, foetal distress, and hypoxia. CONCLUSIONS: Esotropia is the most common type of strabismus in psychomotor retardation. The variability of squint magnitude is a characteristic in these patients. The moderate variability is the most frequent in both esotropia and exotropia. The most common refractive error is hyperopic astigmatism in esotropia and the myopic kind in exotropia. PMID- 26259745 TI - [High frequency of ancestral allele of the TJP1 polymorphism rs2291166 in Mexican population, conformational effect and applications in surgery and medicine]. AB - BACKGROUND: TJP1 gene encodes a ZO-1 protein that is required for the recruitment of occludins and claudins in tight junction, and is involved in cell polarisation. It has different variations, the frequency of which has been studied in different populations. In Mexico there are no studies of this gene. These are required because their polymorphisms can be used in studies associated with medicine and surgery. Therefore, the aim of this study was to estimate the frequency of alleles and genotypes of rs2291166 gene polymorphism TJP1 in Mexico Mestizos population, and to estimate the conformational effect of an amino acid change. MATERIAL AND METHODS: A total of 473 individuals were included. The rs2291166 polymorphism was identified PASA PCR-7% PAGE, and stained with silver nitrate. The conformational effect of amino acid change was performed in silico, and was carried out with servers ProtPraram Tool and Search Database with Fasta. RESULTS: The most frequent allele in the two populations is the ancestral allele (T). A genotype distribution similar to other populations was found. The polymorphism is in Hardy-Weinberg, p>0.05. Changing aspartate to alanine produced a conformational change. CONCLUSIONS: The study reveals a high frequency of the ancestral allele at rs2291166 polymorphism in the Mexican population. PMID- 26259746 TI - [Axillary hidrosadenitis due to Leishmania: Case report and literature review]. AB - BACKGROUND: Hidradenitis is a disorder where abscesses appear after the infection of the apocrine sweat glands. It is located normally in the axillae, groin, perineal region, and the scalp. CLINICAL CASE: A 37 year old male was referred by his GP to the General Surgery Department with axillary hidradenitis which had evolved over the years. The physical examination shows signs of hidradenitis in both axillae, with a noticeable suppurative hidradenitis in the right armpit. En bloc extirpation was performed to remove the whole affected area. The pathological examination revealed a cutaneous leishmaniasis. Subsequently, fucidin was administered topically, as well as local infiltrations of one millilitre of GlucantimeTM. DISCUSSION: Hidradenitis normally appears in intertriginous areas and its manifestation is accompanied by recurrent subcutaneous nodules. The incidence rate in females is three times higher than in males. The isolated Hidradenitis caused by Leishmania is a rare condition presented only in endemic areas or in immunocompromised patients, such as HIV infected patients. Clinical manifestations can be different and the diagnosis can be confirmed through haematoxylin-eosin. The main pattern displays a disorganised granuloma without necrosis. Systemic or topical treatment can be applied. Immunotherapy treatment is the most common. CONCLUSIONS: Hidradenitis caused by Leishmania in HIV-negative patients is a rare condition. Therefore it is important to perform a good histological diagnosis and to administer the right treatment. PMID- 26259747 TI - Spatial interactions between consecutive manual responses. AB - We have shown that the latency to initiate a reaching movement is increased if its direction is the same as a previous movement compared to movements that differ by 90 degrees or 180 degrees (Cowper-Smith and Westwood in Atten Percept Psychophys 75:1914-1922, 2013). An influential study (Taylor and Klein in J Exp Psychol Hum Percept Perform 26:1639-1656, 2000), however, reported the opposite spatial pattern for manual keypress responses: repeated responses on the same side had reduced reaction time compared to responses on opposite sides. In order to determine whether there are fundamental differences in the patterns of spatial interactions between button-pressing responses and reaching movements, we compared both types of manual responses using common methods. Reaching movements and manual keypress responses were performed in separate blocks of trials using consecutive central arrow stimuli that directed participants to respond to left or right targets. Reaction times were greater for manual responses made to the same target as a previous response (M = 390 ms) as compared to the opposite target (M = 365 ms; similarity main effect: p < 0.001) regardless of whether the response was a reaching movement or a keypress response. This finding is broadly consistent with an inhibitory mechanism operating at the level of motor output that discourages movements that achieve the same spatial goal as a recent action. PMID- 26259748 TI - Trigeminal nerve stimulation modulates brainstem more than cortical excitability in healthy humans. AB - Multiple sites in the central nervous system (CNS) have been hypothesized to explain the beneficial effects of transcutaneous trigeminal nerve stimulation (TNS) on several disorders. This work investigated the acute effects of TNS on the excitability of brainstem and intracortical circuits, as well as on sensorimotor integration processes at cortical level in physiological conditions. Brainstem excitability was evaluated in seventeen healthy subjects measuring the R1 and R2 areas of the blink reflex (BR) and its recovery cycle, with cortical excitability and sensorimotor integration assessed by probing short-interval (SICI) and long-interval (LICI) intracortical inhibition, with short-interval (SICF), intracortical facilitation (ICF), short-latency (SAI) and long-latency (LAI) inhibition measuring motor potentials evoked in the first dorsal interosseous muscle by TMS of the contralateral motor cortex. Neurophysiological parameters were assessed, in seventeen healthy subjects, before and after cyclic 20-min TNS delivered bilaterally to the infraorbital nerve. After TNS, the area of the R2 was significantly reduced (p = 0.018). By contrast, R1 area and R2 recovery cycle were unaffected. Similarly, SICI, ICF, LICI, SICF, SAI and LAI appeared unaltered after TNS. These data suggest that, in normal subjects, TNS mainly acts on brainstem polysynaptic circuits mediating the R2 component of the BR and plays a minor role in modifying the activity of higher-level structures involved in the R2 recovery cycle and in modulation of cortical excitability. A further investigation of a chronic TNS-induced effect may disclose a higher potential for TNS in producing measurable after effects on its CNS targets. PMID- 26259749 TI - Quick foot placement adjustments during gait: direction matters. AB - To prevent falls, adjustment of foot placement is a frequently used strategy to regulate and restore gait stability. While foot trajectory adjustments have been studied during discrete stepping, online corrections during walking are more common in daily life. Here, we studied quick foot placement adjustments during gait, using an instrumented treadmill equipped with a projector, which allowed us to project virtual stepping stones. This allowed us to shift some of the approaching stepping stones in a chosen direction at a given moment, such that participants were forced to adapt their step in that specific direction and had varying time available to do so. Thirteen healthy participants performed six experimental trials all consisting of 580 stepping stones, and 96 of those stones were shifted anterior, posterior or lateral at one out of four distances from the participant. Overall, long-step gait adjustments were performed more successfully than short-step and side-step gait adjustments. We showed that the ability to execute movement adjustments depends on the direction of the trajectory adjustment. Our findings suggest that choosing different leg movement adjustments for obstacle avoidance comes with different risks and that strategy choice does not depend exclusively on environmental constraints. The used obstacle avoidance strategy choice might be a trade-off between the environmental factors (i.e., the cost of a specific adjustment) and individuals' ability to execute a specific adjustment with success (i.e., the associated execution risk). PMID- 26259750 TI - Never in mitosis gene A-related kinase 6 and aurora kinase A: New gene biomarkers in the conversion from ulcerative colitis to colorectal cancer. AB - Ulcerative colitis (UC) is an important risk factor for colorectal cancer (CRC). Histone modifications are one of the epigenetic mechanisms that may have key roles in the carcinogenesis of CRC. At present, there are no studies comparing histone modification patterns of UC and CRC in the literature. Therefore the aim of the present study was to investigate whether genes, particularly those involved in histone modification, have value in patient monitoring with regards to CRC development in UC. Key gene expressions of the histone modification enzyme were assessed and compared in CRC, UC and control groups using the RT-PCR array technique. Patients were divided into subgroups based on the extent and duration of the disease and inflammatory burden, which are considered risk factors for CRC development in UC patients. In UC and CRC groups, a significantly higher overexpression of the NEK6 and AURKA genes compared to the control group was identified. In addition, there was a significantly higher overexpression of HDAC1 and PAK1 genes in the UC group, and of HDAC1, HDAC7, PAK1 and AURKB genes in the CRC group. NEK6, AURKA, HDAC1 and PAK1 were significantly overexpressed in patients with a longer UC duration. Overexpression of AURKA and NEK6 genes was significantly more pronounced in UC patients with more extensive colon involvement. HDAC1, HDAC7, PAK1, NEK6, AURKA and AURKB are important diagnostic and prognostic markers involved in the carcinogenesis of CRC. HDAC1, PAK1, NEK6 and AURKA may be considered as diagnostic markers to be used in CRC screening for UC patients. PMID- 26259751 TI - Treatment and Prognosis of Rare Breast Cancers. AB - Management algorithms for invasive and non-invasive ductal and lobular breast carcinomas are well-established. Because of their very nature, rare histologic types of primary breast cancers are not represented in practice guidelines and thus present a challenge to the practicing clinician who must make recommendations for surgical treatment, axillary staging, and adjuvant therapy, as well as counsel patients as to their expected disease course and prognosis. Herein, case reports and published series of rare types of primary breast cancer including adenoid cystic, mucoepidermoid, metaplastic, squamous, neuroendocrine, encysted papillary, and micropapillary types will be reviewed to provide a basis for treatment planning for patients presenting with these rare primary breast malignancies. PMID- 26259752 TI - Contralateral Prophylactic Mastectomy: Challenging Considerations for the Surgeon. AB - The use of both bilateral prophylactic mastectomy and contralateral prophylactic mastectomy (CPM) has increased significantly during the last decade. Various risk models have been developed to identify patients at increased risk for breast cancer. The indications for bilateral prophylactic mastectomy for patients without a diagnosis of breast cancer include high risk from mutation in BRCA or other breast cancer predisposition gene, very strong family history with no identifiable mutation, and high risk based on breast histology. Additionally, the use of CPM has more than doubled in the last decade, and this increase is noted among all stages of breast cancer, even in patients with ductal carcinoma in situ (stage 0). The risk of contralateral breast cancer often is overestimated by both patients and physicians. Nevertheless, specific risk factors are associated with an increased risk of contralateral breast cancer, including BRCA or other genetic mutation, young age at diagnosis, lobular histology, family history, and prior chest wall irradiation. Although CPM reduces the incidence of contralateral breast cancer, the effect on disease-free survival and, more importantly, overall survival is questionable and underscored by the fact that the reason most patients choose CPM is to achieve "peace of mind." Newer and effective reconstructive options have made the procedure more attractive. This panel addresses the indications and rationale for bilateral prophylactic mastectomy and CPM, the decision-making process by patients, and ethical considerations. Changes in the physician-patient relationship during the past few decades have altered the approach, and ethical considerations are paramount in addressing these issues. PMID- 26259754 TI - Improving the Success Rate of Repeat Sentinel Node Biopsy in Recurrent Breast Cancer. AB - PURPOSE: Repeat sentinel node biopsy (SNB) is an alternative to axillary lymph node dissection (ALND) for axillary staging in recurrent breast cancer. This study was conducted to determine factors associated with technical success of repeat SNB. METHODS: A total of 536 patients with locally recurrent nonmetastatic breast cancer underwent lymphatic mapping (LM) and repeat SNB in 29 Dutch hospitals. RESULTS: A total of 179 patients previously underwent breast conserving surgery (BCS) with SNB, 262 patients BCS with ALND and 61 patients mastectomy, 35 with SNB and 26 with ALND. Another 34 patients underwent breast surgery without axillary interventions. A repeat sentinel node (SN) was identified in 333 patients (62.1 %) and was successfully removed in 235 (53.5 %). The overall repeat SN identification rate was 62.1 %, varying from 35 to 100 % in the participating hospitals. Previous radiotherapy of the breast [odds ratio (OR) 0.16; 95 % confidence interval (CI) 0.03-0.84], subareolar tracer injection (OR 0.34; 95 % CI 0.16-0.73), and a 2-day LM protocol (OR 0.57; 95 % CI 0.33-0.97) after previous BCS were independently associated with failure of SN identification. Injection of a larger amount of tracer (>180 MBq) led to a higher identification rate (OR 4.40; 95 % CI 1.45-13.32). CONCLUSIONS: Repeat SNB is a technically feasible procedure for axillary staging in recurrent breast cancer patients. Previous radiotherapy appears to be associated with failure of SN identification. Injection with a larger amount of tracer (>180 MBq) leads to a higher identification rate; subareolar injection and a 2-day LM protocol after previous BCS appear to be less adequate. PMID- 26259753 TI - Repeat Hepatectomy for Breast Cancer Liver Metastases. AB - BACKGROUND: Resection of breast cancer liver metastases (BCLM) combined with systemic treatment is increasingly accepted as a therapeutic option; however, the potential benefit of repeat hepatectomy for recurrent BCLM is unknown. METHODS: All consecutive female patients who underwent liver resection for BCLM at our center between January 1985 and December 2012 were included. Patients who had a single hepatectomy (N = 120) were compared with those who also underwent repeat hepatectomy (N = 19). Patients were selected for repeat hepatectomy based on operability and disease control. Prognostic factors of survival after repeat hepatectomy were determined. RESULTS: Median overall survival since first hepatectomy was 35 months, with a 3- and 5-year survival rate of 50 and 38 %, respectively. Overall survival following repeat hepatectomy was 64 and 46 % at 3 and 5 years, respectively. From the time of first hepatectomy, patients who underwent repeat hepatectomy had a better survival than those who had only one hepatectomy (95 and 84 vs. 50 and 38 % at 3 and 5 years, respectively) (p = 0.002). Median survival was 35 and 100 months, respectively, and median survival since the diagnosis of BCLM was 51 and 112 months in the single and repeat hepatectomy groups, respectively. Since the time of diagnosis, overall 3-, 5-, and 7-year survival rates were 75, 57, and 44 %, respectively, for all 139 patients. Improved overall survival after repeat hepatectomy was related to a time interval between breast cancer diagnosis and first hepatectomy of >2 years, a limited hepatectomy, solitary liver metastasis, positive progesterone receptor status, and chemotherapy following repeat hepatectomy. Patients with single BCLM at first hepatectomy had a 3- and 5-year overall survival rate of 76 and 76 % compared with 51 and 17 % in patients with multiple metastases (p = 0.023). CONCLUSION: In selected patients with BCLM, repeat hepatectomy for liver recurrence combined with systemic treatment provided survival rates comparable to those after first hepatectomy. PMID- 26259755 TI - Serum VEGF-A and Tumor Vessel VEGFR-2 Levels Predict Survival in Caucasian but Not Asian Patients Undergoing Resection for Gastric Adenocarcinoma. AB - BACKGROUND: Clinical trials of agents targeting the vascular endothelial growth factor A (VEGF-A) pathway in gastric adenocarcinoma (GA) suggest that these therapies may have varying efficacy in different races. METHODS: VEGF-A in serum and/or VEGF receptor 2 (VEGFR-2) in CD31-positive tumor vessels (VEGFR-2/CD31) were measured in 118 Caucasians and 263 Asians who underwent gastric resection at two institutions and correlated with overall survival (OS). Blood was drawn before any treatment. Patients receiving neoadjuvant treatment were excluded from VEGFR-2 analysis. RESULTS: Compared with Asians, Caucasians were older (mean age 66-73 vs 59-62 years), had more proximal tumors, and had more advanced TNM stage. In the VEGF-A cohort, Caucasians had a median VEGF-A level that was 95 % higher than that of Asians and a much higher standard deviation (88 +/- 6.206 vs 45 +/- 76 pg/ml, p < 0.001). The 5-year OS for patients with low versus high VEGF-A levels was 72 versus 43 % in Caucasians (p = 0.001) and 86 versus 77 % in Asians (p = 0.236). In the VEGFR-2 cohort, OS was worse in Caucasians with high VEGFR 2/CD31 levels (49 vs 73 %, p = 0.038), while there was no significant difference in OS in Asians (80 vs 90 %, p = 0.119). On multivariate analyses of significant prognostic factors (excluding treatment factors and margin status), serum VEGF-A and tumor VEGFR-2/CD31 levels were independent predictors of OS only in Caucasians. CONCLUSIONS: In patients with resectable GA, VEGF-A and VEGFR-2/CD31 levels are independent predictors of OS in Caucasians but not in Asians, suggesting varying importance of this pathway in GA progression among different races. PMID- 26259756 TI - A Study Comparing Free-Flap Reconstruction via the Retroauricular Approach and the Traditional Transcervical Approach for Head and Neck Cancer: A Matched Case Control Study. AB - BACKGROUND: Free-flap reconstruction via a retroauricular approach (RRA) after robot-assisted neck dissection (RAND) could have cosmetic benefits. This study aimed to compare the surgical outcomes of free-flap reconstruction via a RRA and via a transcervical approach in head and neck cancer. METHODS: For this matched case-control study, 50 patients with head and neck cancer requiring free-flap reconstruction were divided into two groups: those reconstructed via a RRA group and those reconstructed via a transcervical approach (RTA group). The total operation time for free-flap reconstruction, the flap survival rate, the length of the hospital stay, the complications, and the scar satisfaction scores were compared between the two groups. RESULTS: The RRA group comprised 25 patients, and the RTA group had 25 patients. The mean operation time for reconstruction was 288 +/- 77 min in the RRA group and 250 +/- 98 min in the RTA group (p = 0.132). Flap failure occurred for two patients in the RRA group (8 %) and for one patient in the RTA group (4 %) (p = 1.000). The mean hospital stay was 21 +/- 18 days in the RRA group and 23 +/- 14 days in the RTA group (p = 0.669). The complications were comparable between the two groups. However, the overall scar satisfaction was significantly higher in the RRA group (p = 0.000). CONCLUSIONS: For patients with head and neck cancer, RRA has better cosmetic outcomes than RTA. The RRA approach could be used for select patients who undergo RAND and prefer to avoid a visible anterior neck scar. PMID- 26259757 TI - Factors Predictive of Emergency Department Visits and Hospitalization Following Thyroidectomy and Parathyroidectomy. AB - BACKGROUND: This study aimed to determine the incidence and risk factors for emergency department (ED) visits and unplanned hospitalization after thyroid and parathyroid surgery. METHODS: A retrospective study of all patients who underwent thyroidectomy or parathyroidectomy from 2007 to 2014 was conducted to assess for ED visits or unplanned hospitalization within 30 days after surgery. Uni- and multivariate analyses were used to identify risk factors for ED visits and hospitalization. RESULTS: Of 864 patients who underwent thyroidectomy (n = 673) or parathyroidectomy (n = 191), 96 (11.1 %) had an ED visit and 41 (4.7 %) were hospitalized within 30 days after surgery. Univariate analysis showed hypocalcemia (p = 0.001), younger age (p = 0.02), total thyroidectomy (p = 0.01), and lack of private health insurance (p = 0.005) to be predictive of an ED visit and hypocalcemia (p = 0.0001), Hashimoto's thyroiditis (p = 0.049), total thyroidectomy (p = 0.005), and African American race (p = 0.03) were predictive of hospitalization after thyroidectomy. Multivariate analysis showed younger age (odds ratio [OR] 1.5 per 10-year decrease in age; p = 0.002; 95 % confidence interval [CI] 1.1-1.8) and Medicare insurance (OR 2.7; p = 0.01; 95 % CI 1.3-5.7) to be independently associated with an ED visit, and hypocalcemia (OR 4.7; p < 0.001; 95 % CI 2.2-11.0) was the only independent factor associated with hospitalization after thyroidectomy. Univariate analysis showed hypocalcemia, renal hyperparathyroidism, and multiglandular disease to be predictive of an ED visit and hospitalization after parathyroidectomy. The sample size for parathyroidectomy was too small for multivariate analysis. CONCLUSIONS: Targeted strategies for transitions of care for patients with postoperative hypocalcemia may help to reduce ED visits and hospitalization after thyroidectomy and parathyroidectomy. PMID- 26259758 TI - Indocyanine Green Fluorescence for Sentinel Lymph Node Detection in Early Breast Cancer. PMID- 26259759 TI - Tackling social factors is key in reducing cardiovascular disease, say US heart doctors. PMID- 26259760 TI - Therapy-related B-lymphoblastic leukemia associated with Philadelphia chromosome and MLL rearrangement: Single institution experience and the review of the literature. AB - Therapy related acute lymphoblastic leukemia (t-ALL) of B cell origin is rare and constitutes approximately 2% of all ALL. Previously compiled data on the complete cytogenetic analysis of 48 t-B-ALL cases suggested that MLL rearrangement at 11q23 gene locus is the most common abnormality. Philadelphia chromosome (Ph) and a normal karyotype were reported as the second and third most common karyotypes, respectively. We investigated cytogenetic karyotypes of six t-B-ALL cases with a pre-B cell immunophenotype. Ph + t-B-ALL was noted in four of six patients previously treated with radiation and/or chemotherapy. In addition, one case demonstrated MLL rearrangement at 11q23 locus while one case demonstrated normal cytogenetic karyotype. Five of the six t-B-ALL patients had persistent leukemia following initiation of chemotherapy for secondary leukemia with survival ranging from 10 to 21 months. To our knowledge, only fourteen patients with Ph + t-B-ALL have been described in the literature. In the current study, three of four cases with Ph + t-B-ALL were associated with treated breast carcinoma while one patient was treated for Hodgkin lymphoma. All four patients had undergone radiation therapy. The results may indicate a plausible association between Ph+t-B-ALL and prior radiation exposure. PMID- 26259761 TI - The Complexity of Complex Patients. PMID- 26259763 TI - Capsule Commentary on Haas et al., Provider Attitudes and Screening Practices Following Changes in Breast and Cervical Cancer Screening Guidelines. PMID- 26259764 TI - Farming, Ranching, Research: Patient Engagement on the High Plains. PMID- 26259762 TI - Effect of Patient Navigation on Breast Cancer Screening Among African American Medicare Beneficiaries: A Randomized Controlled Trial. AB - BACKGROUND: There is growing evidence that patient navigation improves breast cancer screening rates; however, there are limited efficacy studies of its effect among African American older adult women. OBJECTIVE: To evaluate the effect of patient navigation on screening mammography among African American female Medicare beneficiaries in Baltimore, MD. DESIGN: The Cancer Prevention and Treatment Demonstration (CPTD), a multi-site study, was a randomized controlled trial conducted from April 2006 through December 2010. SETTING: Community-based and clinical setting. PARTICIPANTS: The CPTD Screening Trial enrolled 1905 community-dwelling African American female Medicare beneficiaries who were >=65 years of age and resided in Baltimore, MD. Participants were recruited from health clinics, community centers, health fairs, mailings using Medicare rosters, and phone calls. INTERVENTIONS: Participants were randomized to either: printed educational materials on cancer screening (control group) or printed educational materials + patient navigation services designed to help participants overcome barriers to cancer screening (intervention group). MAIN MEASURE: Self-reported receipt of mammography screening within 2 years of the end of the study. KEY RESULTS: The median follow-up period for participants in this analysis was 17.8 months. In weighted multivariable logistic regression analyses, women in the intervention group had significantly higher odds of being up to date on mammography screening at the end of the follow-up period compared to women in the control group (odds ratio [OR] 2.26, 95 % confidence interval [CI]1.59-3.22). The effect of the intervention was stronger among women who were not up to date with mammography screening at enrollment (OR 3.63, 95 % CI 2.09-6.38). CONCLUSION: Patient navigation among urban African American Medicare beneficiaries increased self-reported mammography utilization. The results suggest that patient navigation for mammography screening should focus on women who are not up to date on their screening. PMID- 26259765 TI - Effect of dietary vanadium and vitamin C on egg quality and antioxidant status in laying hens. AB - This study assessed the effect of dietary vanadium (V) and vitamin C (VC) on production performance, egg quality and antioxidant status in laying hens. A total of 360 laying hens (31-week-old) were randomly allotted into a 3 * 3 factorial arrangement treatments (four replicates and 10 chicks per replicate) with three levels of dietary V (0, 5 and 10 mg/kg) and three levels of vitamin C (0, 50 and 100 mg/kg) for 12 weeks. The effect of V and VC did not alter egg production, egg weight, average daily feed intake and feed conversion ratio during 1-12 week. Albumen height and Haugh unit value were linearly decreased (p < 0.001) by addition of V, whereas the effect of 100 mg/kg VC was observed to counteract (p < 0.05) this effect in V-containing treatments during 1-12 week. Hens fed V-containing diet laid lighter (linear effect, p < 0.05) coloured eggs (higher lightness value, lower redness and yellowness value), and the VC exerted no influence on it during 1-12 week. The serum superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities, ability to inhibit hydroxyl radical, were significantly decreased, and the malondialdehyde (MDA) and V contents were increased (p < 0.05) by effect of V during 4, 8 and 12 week. The effect of VC alone and the interactive effect between VC and V were shown to increase serum (p < 0.05) SOD activity in 4 week and decrease MAD levels in 12 week. The result indicate that V decreased the egg quality and caused the oxidative stress at level of 5 mg/kg and 10 mg/kg, and the addition of 100 mg/kg vitamin C can alleviate its egg quality reduction effect and can mitigate the oxidative stress to some extent. PMID- 26259766 TI - Early Results of Physician Modified Fenestrated Stent Grafts for the Treatment of Thoraco-abdominal Aortic Aneurysms. AB - OBJECTIVES: The aim was to determine whether physician modified stent grafts (PMSGs) are safe and effective for the treatment of high risk patients with thoraco-abdominal aortic aneurysms (TAAAs). DESIGN: This was a retrospective single institution study. MATERIAL: Consecutive patients with TAAA undergoing endovascular repair using a PMSG between January 2012 and June 2014 were evaluated. METHODS: Fenestrations to preserve branch vessels were created in TX2 thoracic (Cook Medical) stent grafts. Pre- intra- and post-operative data were recorded by means of a prospectively maintained database. RESULTS: Eleven high risk patients with TAAA (type I, n = 4; type III, n = 3; type IV, n = 3; type V, n = 1) underwent fenestrated endovascular repair using PMSGs. Indications were painful aneurysm (n = 5), >70 mm rapidly enlarging aneurysm (n = 4), saccular aneurysm (n = 1), and visceral patch false aneurysm after open repair of a type IV TAAA (n = 1). In four asymptomatic patients, an additional fenestration was created for temporary selective sac perfusion and occluded 2-4 weeks later. Median duration for stent graft modifications was 2 hours (range 1-3 hours). The median number of fenestrations was three (range 2-4). One patient died during the post-operative period from colonic ischemia, giving a 9% in hospital mortality rate. Four (36%) patients presented with moderate to severe complications. One (9%) patient presented with a paraparesis that resolved completely after spinal fluid drainage. Among surviving patients, four required early endovascular re intervention for type III endoleak (n = 2), type Ia endoleak (n = 1), or target vessel cannulation failure (n = 1). The median follow up time was 6 months (range 3-20 months). During follow up, no other complications occurred and all target vessels remained patent. One patient presented with a persistent type II endoleak. CONCLUSION: PMSGs provided acceptable short-term results and may be a management option for the treatment of TAAA in selected high risk patients. Durability concerns need to be assessed in additional studies with long-term follow up. PMID- 26259767 TI - Renal Outcome After Open Surgery and Fenestrated Endovascular Aneurysm Repair of Juxta-renal Aneurysms. PMID- 26259768 TI - Are campylobacters now capable of carbo-loading? AB - Campylobacters are a leading cause of gastrointestinal morbidity worldwide and the majority of human infections are triggered by eating foods contaminated with Campylobacter jejuni or Campylobacter coli. Campylobacters are equally notorious for their ability to mimic human glycoconjugate structures and for their capacity to synthesize both N- and O-linked glycoproteins. These species were once considered to be asaccharolytic, but it was recently shown that several strains possess a pathway for fucose uptake and metabolism, providing those isolates with a competitive advantage in vivo. Vorwerk et al. have now demonstrated through isotopologue profiling that certain strains of C. coli and C. jejuni are capable of glucose catabolism through the Entner-Doudoroff and pentose phosphate pathways. However, unlike the fate of fucose that has only been shown to be used for nutrition, glucose can be metabolized or incorporated into select amino acids and glycoconjugates. This discovery now provides researchers with the opportunity to introduce metabolically labeled sugars into campylobacters to study glycoconjugate biosynthesis within the cell. In addition, Vorwerk et al. add to the metabolic arsenal of campylobacters further highlighting the nutritional diversity among strains, even within the same species. PMID- 26259769 TI - RNA rewriting, recoding, and rewiring in human disease. AB - ADAR (adenosine deAminase acting on RNA) editases catalyze the deamination of adenosine to inosine (A-to-I), a post-transcriptional modification that alters coding and non-coding RNA stability and function. ADAR editases such as ADAR1 have recently been shown to play a key role in normal stem cell maintenance. While ADAR mutations are associated with hereditary autoimmune diseases such as Aicardi-Goutieres syndrome, ADAR copy-number alterations and editase activation have been associated with progression of a broad array of malignancies. In this review we discuss evidence linking aberrant A-to-I editing to cancer and other degenerative diseases, and the mechanisms that may be targeted by novel therapeutic strategies. PMID- 26259770 TI - Repeated Intramyocardial Bone Marrow Cell Injection in Previously Responding Patients With Refractory Angina Again Improves Myocardial Perfusion, Anginal Complaints, and Quality of Life. AB - BACKGROUND: Intramyocardial bone marrow cell injection is associated with improvements in myocardial perfusion and anginal symptoms in patients with refractory angina pectoris. This study evaluates the effect of repeated intramyocardial bone marrow cell injection in patients with residual or recurrent myocardial ischemia. METHODS AND RESULTS: Twenty-three patients (17 men; 69+/-9 years) who had improved myocardial perfusion after the first injection but had residual or recurrent angina and ischemia on single-photon emission computed tomographic myocardial perfusion imaging were included. Patients again received intramyocardial injection of 100*10(6) autologous bone marrow mononuclear cells, 4.6+/-2.5 years after their first injection. No periprocedural complications occurred. Myocardial perfusion assessed using single-photon emission computed tomographic myocardial perfusion imaging improved from a summed stress score of 27.3+/-5.8 at baseline to 24.5+/-4.4 at 3 months (P=0.002) and 25.4+/-4.9 at 12 months of follow-up (P=0.002). Perfusion improvement after 3 months was comparable with the effect of the first injection (P=0.379). Anginal complaints improved <=12 months after cell injection in Canadian Cardiovascular Society score (mean change at 3, 6, and 12 months: 0.6+/-0.9%, 0.5+/-0.9%, and 0.6+/ 0.9%, respectively; Pslope=0.007, first versus repeated; P=0.188) and in quality of life score as measured by Seattle Angina Questionnaire (mean change at 3, 6, and 12 months: 7+/-14%, 8+/-14%, and 7+/-15%, respectively; Pslope=0.020, first versus repeated; P=0.126). CONCLUSIONS: Repeated bone marrow cell injection in previously responding patients with refractory angina is associated with improvements in myocardial perfusion, anginal complaints, and quality of life score <=12 months of follow-up. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR2664. PMID- 26259771 TI - Repeat Cell Therapy for Refractory Angina: Deja vu All Over Again? PMID- 26259772 TI - Efficacy and safety of pregabalin in generalised anxiety disorder: A critical review of the literature. AB - The aim of this review is to summarise the literature on the efficacy and safety of pregabalin for the treatment of generalised anxiety disorder (GAD). Of 241 literature citations, 13 clinical trials were identified that were specifically designed to evaluate the efficacy and safety of pregabalin in GAD, including 11 randomised double-blind trials and two open-label studies. Pregabalin efficacy has been consistently demonstrated across the licensed dose range of 150-600 mg/day. Efficacy has been reported for pregabalin monotherapy in elderly patients with GAD, patients with severe anxiety, and for adjunctive therapy when added to a selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor in patients who have failed to respond to an initial course of antidepressant therapy. The two most common adverse events with pregabalin are somnolence and dizziness, both of which appear to be dose-related. Pregabalin appears to have a low potential for causing withdrawal symptoms when long-term therapy is discontinued; however, tapering over the course of at least one week is recommended. A review of available evidence indicates that pregabalin is a well-tolerated and consistently effective treatment for GAD, with a unique mechanism of action that makes it a useful addition to the therapeutic armamentarium. PMID- 26259773 TI - The effects of galantamine and buspirone on sleep structure: Implications for understanding sleep abnormalities in major depression. AB - RATIONALE: The serotonergic and cholinergic systems are jointly involved in regulating sleep, but this balance is theorized to be disturbed in depressed individuals. OBJECTIVE: The goal of this study was to use biological probes in healthy participants, to model the serotonergic/cholinergic imbalance of depression and its associated abnormalities in sleep structure. METHODS: We tested 20 healthy female participants 18-30 years of age on four non-consecutive nights. Participants were given galantamine (a cholinergic agent), buspirone (a serotonergic agonist), both drugs together, or placebo before sleeping. RESULTS: Buspirone suppressed tonic rapid eye movement (REM): There was a significant increase in REM latency (p < 0.001). Galantamine increased tonic REM sleep, leading to more time spent in REM (p < 0.001) and shorter REM latency (p < 0.01). Galantamine and buspirone given together were not significantly different from the placebo night by REM sleep measures, but disrupted sleep more than either drug alone. CONCLUSIONS: These findings are partially consistent with the cholinergic literature about sleep in depression, notably short REM latency, higher percentage of total sleep time spent in REM and increased sleep fragmentation. The prolonged REM latency and reduced percentage of REM with buspirone resembled the effect of selective serotonin reuptake inhibitor antidepressants on REM sleep. PMID- 26259774 TI - Impact of a Multidisciplinary Heart Failure Post-hospitalization Program on Heart Failure Readmission Rates. AB - BACKGROUND: Specialized chronic heart failure (HF) clinics have demonstrated significant reductions in readmissions. Limited evidence is available regarding HF clinics in the immediate post-discharge period. OBJECTIVE: To evaluate the effect of a multidisciplinary HF clinic on 90-day readmission rates and all-cause mortality in those recently discharged from a HF hospitalization. METHODS: In this retrospective cohort study, patients discharged with a primary HF diagnosis who attended the HF postdischarge clinic in 2010-2012 were compared with controls from 2009. During 6 clinic visits, patients were seen by a physician assistant, clinical pharmacist specialist, and case manager, with care overseen by a cardiologist. The program focused on optimizing therapy, identifying HF etiology/precipitating factors, medication titration, education, and medication adherence. The primary outcome was 90-day HF readmission. A multivariate Cox proportional hazards model was used to compare outcomes. RESULTS: Among the 277 patients (144 clinic, 133 control) in the study, 7.6% of patients in the clinic and 23.3% of patients in the control group were readmitted for HF within 90 days (aHR (adjusted hazard ratio) = 0.17; 95% CI = 0.07-0.41; P < 0.001; ARR (absolute risk reduction) = 15.7%; NNT (number needed to treat) = 7). Clinic patients had lower 90-day time-to-first HF readmission or all-cause mortality (9.0% vs 28.6%; aHR = 0.28; 95% CI = 0.06-0.31; P < 0.001; ARR = 19.6%; NNT = 6). CONCLUSIONS: The multidisciplinary HF posthospitalization outpatient program was associated with a significant reduction in 90-day HF readmissions in patients who were recently discharged from a HF hospitalization. PMID- 26259775 TI - Reply: Pulmonary Embolism After Early Change From Rivaroxaban to Aspirin Following Total Knee Replacement in an Obese Patient. PMID- 26259776 TI - A fluorescent sensor with a detection level of pM for Cd(2+) and nM for Cu(2+) based on different mechanisms. AB - A fluorescent sensor L, which showed turn-on response towards Cd(2+) with a detection limit of 1.9 * 10(-12) mol L(-1) in acetonitrile-H2O buffer solution based on the PET process and turn-off response toward Cu(2+) with a detection limit of 4.9 * 10(-9) mol L(-1) in pure water at pH 3.5 based on electrostatic effects, was developed. PMID- 26259777 TI - Application of data screening to drug exposure in large risk factor studies of birth defects. AB - BACKGROUND: Birth defects are the leading cause of infant death. While causes of most are unknown, those that might be due to medication use are among the most preventable. This study describes an approach to identifying those medications that most warrant attention by using a "screen" program that calculates odds ratios for pairs of exposures and specific birth defects. METHODS: We discuss the development of this tool and illustrate its application to two large risk factor studies, the Slone Epidemiology Center's Birth Defects Study and the Centers for Disease Control and Prevention's National Birth Defects Prevention Study, ideal settings for the systematic study of risks and relative safety of drugs in relation to birth defects while recognizing the inherent limitations of such an approach. RESULTS: Suggestions for establishing criteria for exposures and outcomes that balance the need for specific details with the practical considerations of sample size and volume of output are presented. Selection of appropriate exposure reference categories and control groups is also discussed, as well as the need to address potential confounding. An example that motivated a detailed investigation of possible associations between a medication (butalbital) and selected specific birth defects is provided. CONCLUSION: While screening programs such as the one described can be a valuable tool for exploring potential associations in large data bases, they must be applied with caution. The issue of multiple testing and chance findings is a major concern. While statistics are a necessary component, human judgment must be an integral part of the process. PMID- 26259778 TI - Microvascular invasion patterns affect survival in hepatocellular carcinoma patients after second hepatectomy. AB - BACKGROUND: Microvascular invasion (MVI) is an important risk factor for survival of patients with hepatocellular carcinoma (HCC) after hepatectomy. However, its impact on patients with recurrent HCC who receive a second hepatectomy is unknown. METHODS: We enrolled 167 patients with HCC who underwent a second hepatectomy because of intrahepatic recurrences. We compared the patients' demographic, tumor, and pathologic characteristics with 766 cases of original hepatectomy. We analyzed the possible risk factors for survival after the first and second hepatectomies and the influence of different MVI patterns on patients' survival after the second hepatectomy. RESULTS: The median overall survival was comparable between the first and second hepatectomy groups, 34 (3-84) mo versus 27 (3-57) mo, P = 0.09. For patients who underwent a first hepatectomy, the presence of macro-VI or MVI, an early recurrence pattern, and a total tumor diameter >5 cm were independent risk factors. For survival after the second hepatectomy, MVI patterns that were positive-positive or negative-positive and a total recurrent tumor diameter >5 cm were significant risk factors for survival. CONCLUSIONS: A second hepatectomy provides satisfying survival for patients with intrahepatic recurrence of HCC after the initial operation. Different MVI patterns affect survival after the second hepatectomy. Because MVI represents the biological behavior of HCC, we place a high premium on the clinical value of MVI after each hepatectomy. PMID- 26259779 TI - Uniaxial cyclic stretch stimulates TRPV4 to induce realignment of human embryonic stem cell-derived cardiomyocytes. AB - Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) in culture are randomly organized and do not typically show directional alignment. In the present study, we used uniaxial cyclic stretch to facilitate the alignment of cultured human embryonic stem cell-derived cardiomyocytes (hESC-CMs), so that these cells can be more adult-like for potential future application in drug screening and in vitro studies of cardiac function. We then explored the functional role of mechanosensitive TRPV4 channels in cyclic stretch-induced realignment of hESC-CMs. RT-PCR, immunoblots and immunostaining detected TRPV4 expression in these cells. 4alpha-phorbol 12,13-didecanoate (4alpha-PDD), a TRPV4 agonist, elicited a cytosolic Ca(2+) ([Ca(2+)]i) rise, the effect of which was abolished by TRPV4 inhibitors RN1734 and HC067047, and a TRPV4 dominant negative construct. These results confirmed the functional presence of TRPV4 in these cells. Importantly, longitudinal stretch was found to induce a [Ca(2+)]i rise, the effect of which was inhibited by TRPV4 antagonists. Furthermore, uniaxial cyclic stretch for 2h induced realignment of hESC-CMs in the direction transverse to the direction of stretch, the effect of which was also abolished by TRPV4 antagonists. Akt phosphorylation was found to be a downstream signal of TRPV4. Taken together, these data strongly suggest endogenous TRPV4 channels as a mechanosensor, mediating cyclic stretch-induced realignment of hESC-CMs. PMID- 26259780 TI - Increased ID4 expression, accompanied by mutant p53 accumulation and loss of BRCA1/2 proteins in triple-negative breast cancer, adversely affects survival. AB - AIMS: Breast cancer 1 (BRCA1) expression is down-regulated in a significant proportion of non-hereditary breast cancers, in the absence of any mutation. This phenomenon is more pronounced in oestrogen (ER)-negative tumours. Recent studies have suggested that inhibitor of DNA binding 4 (ID4), as well as p53, participate in the transcriptional regulation of BRCA1. METHODS: Immunohistochemical expression of ID4, BRCA1, BRCA2 and p53 in 699 women with triple-negative breast cancer was investigated using tissue microarrays. The prognostic role of these biomarkers was also evaluated. Survival outcomes were estimated with the Kaplan Meier method and compared between groups with log-rank statistics. RESULTS: Loss of BRCA1 and BRCA2 expression and overexpression of ID4 and p53 was observed in 75%, 90%, 95% and 66% of tumours, respectively. ID4 expression was increased in higher tumour grade (P < 0.001) and was associated significantly with basal-like subtype (P < 0.001), BRCA2 down-regulation (P = 0.037) and p53 accumulation (P < 0.001). Patients with strong ID4 expression displayed worse disease-free survival in both triple-negative breast cancers (P = 0.041) and basal-like triple-negative breast cancers (P = 0.026). CONCLUSION: There is frequent ID4 expression and concomitant loss of BRCA proteins in triple-negative breast cancer. We hypothesize that strong ID4 expression could be useful as a prognostic marker in triple-negative breast cancer, predicting early tumour recurrence. PMID- 26259781 TI - Distinguishing Feigned From Sincere Performance in Psychophysical Pain Testing. AB - Self-report, the most widely used, gold standard measurement of pain, is crucial for pain research, diagnosis, and management. However, there are no accurate, reliable methods for detecting dishonesty in self-reports when there is incentive for pain deception. We introduce a novel approach to detecting pain deception by analyzing performance patterns of honest and dishonest psychophysical pain testing. Warmth sensation threshold (WST) and heat pain threshold (HPT) were measured in healthy individuals (N = 37) under 2 conditions: standard instruction (ie, provide sincere reports) and instructions to simulate intense pain (i.e., provide feigned reports) with the intention of deceiving. In the feigned compared with sincere condition, participants had significantly increased WST and decreased HPT. Repeatability and variability indices were indistinguishable between conditions. In a second, separate cohort (N = 24), measurements were repeated with the addition of a sensory interference to influence task performance. When sensory interference during HPT measurement was introduced, feigned pain reports had significantly higher variability and poorer repeatability compared with sincere reports and were distinguishable from sincere reports, with high sensitivity (83%) and specificity (84%). The statistical properties of psychophysical performance under sensory interference provide a method for identifying feigned performance and could be applied to evaluations of pain malingering. PERSPECTIVE: This article introduces a method to detect whether individuals are being dishonest in psychophysical pain testing. The method could help clinicians to detect chronic pain malingering in contexts in which there is incentive to deceive. PMID- 26259783 TI - Biological barriers--Advanced drug delivery, in vitro modelling, and their implications for infection research. PMID- 26259782 TI - The second virial coefficient as a predictor of protein aggregation propensity: A self-interaction chromatography study. AB - The second osmotic virial coefficients (b2) of four proteins - lysozyme, recombinant human lactoferrin, concanavalin A and catalase were measured by self interaction chromatography (SIC) in solutions of varying salt type, concentration and pH. Protein aggregate sizes based on the initial hydrodynamic radius of the protein solution species present were measured using dynamic light scattering, and the relationship between b2 and protein aggregate size was studied. A linear correlation was established between b2 values and protein aggregate hydrodynamic size for all proteins, and for almost all solution conditions. Aggregate sizes of <~10nm, indicative of non-aggregated protein systems, were consistently observed to have b2 values >0. The observed b2 trends as a function of solution conditions were very much protein dependent, with notable trends including the existence of attractive interactions (negative b2 values) at low ionic strengths for catalase and concanavalin A, and the highly positive b2 values observed for lactoferrin over a wide range of solution conditions, reflecting lactoferrin's innately high stability. It is concluded that the quantification of protein-protein interactions using SIC based b2 data is a potentially valuable screening tool for predicting protein aggregation propensity. PMID- 26259784 TI - The biophysics of piezo1 and piezo2 mechanosensitive channels. AB - The ability to sense mechanical stimuli and elaborate a response to them is a fundamental process in all organisms, driving crucial mechanisms ranging from cell volume regulation up to organ development or regeneration. Nevertheless, only in few cases the underlying molecular players are known. In particular, mammals possess a large variety of mechanoreceptors, providing highly specialized functions in sensory cells, but also several housekeeping molecular systems are involved in the complex mechanism of mechanotransduction. Recently, a new class of almost ubiquitous membrane channels has been identified in mammalians, namely piezo1 and piezo2, that is thought to play a crucial role in the mechanobiology of mammals. This review focuses on recent findings on these novel channels, and highlights open biophysical questions that largely remain to be addressed. PMID- 26259785 TI - Amyloid beta-peptide insertion in liposomes containing GM1-cholesterol domains. AB - Neuronal membrane damage is related to the early impairments appearing in Alzheimer's disease due to the interaction of the amyloid beta-peptide (Abeta) with the phospholipid bilayer. In particular, the ganglioside GM1, present with cholesterol in lipid rafts, seems to be able to initiate Abeta aggregation on membrane. We studied the thermodynamic and structural effects of the presence of GM1 on the interaction between Abeta and liposomes, a good membrane model system. Isothermal Titration Calorimetry highlighted the importance of the presence of GM1 in recruiting monomeric Abeta toward the lipid bilayer. Light and Small Angle X-ray Scattering revealed a different pattern for GM1 containing liposomes, both before and after interaction with Abeta. The results suggest that the interaction with GM1 brings to insertion of Abeta in the bilayer, producing a structural perturbation down to the internal layers of the liposome, as demonstrated by the obtained electron density profiles. PMID- 26259786 TI - Stability and disassembly properties of human naive Hsp60 and bacterial GroEL chaperonins. AB - Human Hsp60 chaperonin and its bacterial homolog GroEL, in association with the corresponding co-chaperonins Hsp10 and GroES, constitute important chaperone systems promoting the proper folding of several mitochondrial proteins. Hsp60 is also currently described as a ubiquitous molecule with multiple roles both in health conditions and in several diseases. Naive Hsp60 bearing the mitochondrial import signal has been recently demonstrated to present different oligomeric organizations with respect to GroEL, suggesting new possible physiological functions. Here we present a combined investigation with circular dichroism and small-angle X-ray scattering of structure, self-organization, and stability of naive Hsp60 in solution in comparison with bacterial GroEL. Experiments have been performed in different concentrations of guanidine hydrochloride, monitoring the dissociation of tetradecamers into heptamers and monomers, until unfolding. GroEL is proved to be more stable with respect to Hsp60, and the unfolding free energy as well as its dependence on denaturant concentration is obtained. PMID- 26259787 TI - 1,25-Dihydroxyvitamin D3 attenuates endotoxin-induced production of inflammatory mediators by inhibiting MAPK activation in primary cortical neuron-glia cultures. AB - BACKGROUND: Neuroinflammation occurs in insulted regions of the brain and may be due to reactive oxygen species (ROS), nitric oxide (NO), cytokines, and chemokines produced by activated glia. Excessive production of neurotoxic molecules causes further neuronal damage. Low levels of vitamin D3 are a risk factor for various brain diseases. METHODS: Using the bacterial endotoxin, lipopolysaccharide (LPS), to induce neuroinflammation in primary cortical neuron glia cultures, we investigated how 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) affected neuroinflammation. RESULTS: LPS (100 ng/ml) induced the accumulation of nitrite and the production of ROS, interleukin (IL)-6, and macrophage inflammatory protein (MIP)-2 in time-dependent manners. Inhibition of p38 and extracellular signal-regulated kinase (ERK) but not c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) by 20 MUM of SB203580, PD98059, and SP600125, significantly reduced LPS-induced ROS production, NO accumulation, and inducible NO synthase (iNOS) expression, respectively. LPS-induced IL-6 and MIP-2 were significantly attenuated by inhibition of p38, ERK, and JNK MAPK. Cotreatment with 1,25(OH)2D3 attenuated LPS-induced ROS production, NO accumulation, and iNOS expression in concentration-dependent manners. 1,25(OH)2D3 also reduced LPS-induced production of IL-6 and MIP-2. Similarly, iNOS, IL-6, and MIP-2 mRNA expression in cells treated with LPS significantly increased, whereas this effect was attenuated by 1,25(OH)2D3. Moreover, LPS-induced phosphorylation of p38, ERK, and JNK MAPK was significantly inhibited by 1,25(OH)2D3. CONCLUSIONS: Our findings indicate that 1,25(OH)2D3 reduced the LPS-stimulated production of inflammatory molecules in neuron-glia cultures by inhibiting MAPK pathways and the production of downstream inflammatory molecules. We suggest that 1,25(OH)2D3 can be used to alleviate neuroinflammation in various brain injuries. PMID- 26259788 TI - The Human Gut Microbiome as a Transporter of Antibiotic Resistance Genes between Continents. AB - Previous studies of antibiotic resistance dissemination by travel have, by targeting only a select number of cultivable bacterial species, omitted most of the human microbiome. Here, we used explorative shotgun metagenomic sequencing to address the abundance of >300 antibiotic resistance genes in fecal specimens from 35 Swedish students taken before and after exchange programs on the Indian peninsula or in Central Africa. All specimens were additionally cultured for extended-spectrum beta-lactamase (ESBL)-producing enterobacteria, and the isolates obtained were genome sequenced. The overall taxonomic diversity and composition of the gut microbiome remained stable before and after travel, but there was an increasing abundance of Proteobacteria in 25/35 students. The relative abundance of antibiotic resistance genes increased, most prominently for genes encoding resistance to sulfonamide (2.6-fold increase), trimethoprim (7.7 fold), and beta-lactams (2.6-fold). Importantly, the increase observed occurred without any antibiotic intake. Of 18 students visiting the Indian peninsula, 12 acquired ESBL-producing Escherichia coli, while none returning from Africa were positive. Despite deep sequencing efforts, the sensitivity of metagenomics was not sufficient to detect acquisition of the low-abundant genes responsible for the observed ESBL phenotype. In conclusion, metagenomic sequencing of the intestinal microbiome of Swedish students returning from exchange programs in Central Africa or the Indian peninsula showed increased abundance of genes encoding resistance to widely used antibiotics. PMID- 26259789 TI - In Vivo Pharmacodynamic Evaluation of an FtsZ Inhibitor, TXA-709, and Its Active Metabolite, TXA-707, in a Murine Neutropenic Thigh Infection Model. AB - Antibiotics with novel mechanisms of action are urgently needed. Processes of cellular division are attractive targets for new drug development. FtsZ, an integral protein involved in cell cytokinesis, is a representative example. In the present study, the pharmacodynamic (PD) activity of an FtsZ inhibitor, TXA 709, and its active metabolite, TXA-707, was evaluated in the neutropenic murine thigh infection model against 5 Staphylococcus aureus isolates, including both methicillin-susceptible and methicillin-resistant isolates. The pharmacokinetics (PK) of the TXA-707 active metabolite were examined after oral administration of the TXA-709 prodrug at 10, 40, and 160 mg/kg of body weight. The half-life ranged from 3.2 to 4.4 h, and the area under the concentration-time curve (AUC) and maximum concentration of drug in serum (Cmax) were relatively linear over the doses studied. All organisms exhibited an MIC of 1 mg/liter. Dose fractionation demonstrated the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC ratio) to be the PD index most closely linked to efficacy (R(2) = 0.72). Dose-dependent activity was demonstrated against all 5 isolates, and the methicillin-resistance phenotype did not alter the pharmacokinetic/pharmacodynamic (PK/PD) targets. Net stasis was achieved against all isolates and a 1-log10 kill level against 4 isolates. PD targets included total drug 24-h AUC/MIC values of 122 for net stasis and 243 for 1-log10 killing. TXA-709 and TXA-707 are a promising novel antibacterial class and compound for S. aureus infections. These results should prove useful for design of clinical dosing regimen trials. PMID- 26259790 TI - Evaluation of Sulfobutylether-beta-Cyclodextrin Exposure in a Critically Ill Patient Receiving Intravenous Posaconazole While Undergoing Continuous Venovenous Hemofiltration. AB - We present a 31-year-old female who had undergone an allogeneic bone marrow transplantation and who was started on intravenous posaconazole for pulmonary mycosis while undergoing continuous venovenous hemofiltration (CVVH). We performed steady-state pharmacokinetic evaluations for both posaconazole and sulfobutylether-beta-cyclodextrin (SBECD). SBECD was effectively removed by CVVH, with observed exposure similar to that for patients with moderate renal impairment. Intravenous posaconazole at standard doses may be utilized in critically ill patients undergoing CVVH without significant risk of SBECD accumulation. PMID- 26259791 TI - Rapid In Vitro Evolution of Human Cytomegalovirus UL56 Mutations That Confer Letermovir Resistance. AB - Letermovir (LMV) is an experimental cytomegalovirus terminase inhibitor undergoing phase 3 clinical trials. Viral mutations have been described at UL56 codons 231 to 369 that confer widely variable levels of LMV resistance. In this study, 15 independent experiments propagating an exonuclease mutant viral strain in escalating LMV concentrations replicated 6 of the 7 published UL56 mutations and commonly elicited additional resistance-conferring mutations at UL56 codons 231, 236, 237, 244, 257, 261, 325, and 329. Mutations were first detected earlier in LMV (median, 3 passages) than in 8 parallel experiments with foscarnet (median, 15 passages). As LMV concentrations increased, the typical initial UL56 change F261L, which confers low-grade resistance, combined or was replaced with mutations conferring higher-grade resistance, eventually enabling normal viral growth in 30 MUM LMV (>5,000-fold the 50% effective concentration [EC50] for the wild type). At high LMV concentrations, the UL56 changes C325F/R were commonly detected, as well as a combination of changes at codons 236, 257, 329, and/or 369. Recombinant viruses containing individual UL56 mutations and combinations were constructed to confirm their resistance phenotypes and normal growth in cell culture. Several double and triple mutants showed much higher LMV resistance than the respective single mutants, particularly those including changes at both codons 236 and 257. The multiplicity of pathways to high-grade LMV resistance with minimal viral growth impact suggests a low viral genetic barrier and the need for close monitoring during treatment of active infection. PMID- 26259792 TI - Carbapenems and Rifampin Exhibit Synergy against Mycobacterium tuberculosis and Mycobacterium abscessus. AB - An effective regimen for treatment of tuberculosis (TB) is comprised of multiple drugs that inhibit a range of essential cellular activities in Mycobacterium tuberculosis. The effectiveness of a regimen is further enhanced if constituent drugs act with synergy. Here, we report that faropenem (a penem) or biapenem, doripenem, or meropenem (carbapenems), which belong to the beta-lactam class of antibiotics, and rifampin, one of the drugs that forms the backbone of TB treatment, act with synergy when combined. One of the reasons (carba)penems are seldom used for treatment of TB is the high dosage levels required, often at the therapeutic limits. The synergistic combination of rifampin and these (carba)penems indicates that (carba)penems can be administered at dosages that are therapeutically relevant. The combination of faropenem and rifampin also limits the frequency of resistant mutants, as we were unable to obtain spontaneous mutants in the presence of these two drugs. The combinations of rifampin and (carba)penems were effective not only against drug-sensitive Mycobacterium tuberculosis but also against drug-resistant clinical isolates that are otherwise resistant to rifampin. A combination of doripenem or biapenem and rifampin also exhibited synergistic activity against Mycobacterium abscessus. Although the MICs of these three drugs alone against M. abscessus are too high to be of clinical relevance, their concentrations in combinations are therapeutically relevant; therefore, they warrant further evaluation for clinical utility to treat Mycobacterium abscessus infection, especially in cystic fibrosis patients. PMID- 26259793 TI - Systematic review and meta-analysis of randomized controlled trials of antibiotics and antiseptics for preventing infection in people receiving primary total hip and knee prostheses. AB - Infection rates in primary (first-time) major joint arthroplasty continue to be a significant issue. The effect of antibiotic and antiseptic prophylaxis on outcomes for this type of surgery has not been adequately reviewed. A systematic search of the main databases for randomized controlled trials (RCTs) evaluating antibiotics and antiseptics was conducted to evaluate the predetermined endpoints of infection, adverse events, costs, quality of life, and concentration levels of antibiotics. A meta-analysis using pooled effect estimates and fixed-effect and random-effect models of risk ratios (RR), calculated with 95% confidence intervals (CI), was utilized. Thirty (30) RCTs examined the effects of antibiotic and antiseptic prophylaxis on infections after primary total hip arthroplasty (THA) (total of 11,597 participants) and total knee arthroplasty (TKA) (total of 6,141 participants). For THA, preoperative systemic intravenous (i.v.) antibiotic prophylaxis may be effective in reducing the incidence of infection after THA from 6 months to >=5 years. For TKA, there is no RCT evidence that antibiotics and/or antiseptics have any effect on infection rate. Preoperative systemic antibiotic prophylaxis in primary THA may be effective at reducing infection rate. There is no evidence that timing, route of administration, or concentration levels have an effect on reducing infections, adverse events, or costs in THA or TKA. Many of the trials included in this study were published in the 1980s and 1990s. Thus, it would be important to replicate a number of them based on current patient demographics and incidence of bacterial resistance. PMID- 26259795 TI - Candida parapsilosis Resistance to Fluconazole: Molecular Mechanisms and In Vivo Impact in Infected Galleria mellonella Larvae. AB - Candida parapsilosis is the main non-albicans Candida species isolated from patients in Latin America. Mutations in the ERG11 gene and overexpression of membrane transporter proteins have been linked to fluconazole resistance. The aim of this study was to evaluate the molecular mechanisms in fluconazole-resistant strains of C. parapsilosis isolated from critically ill patients. The identities of the nine collected C. parapsilosis isolates at the species level were confirmed through molecular identification with a TaqMan qPCR assay. The clonal origin of the strains was checked by microsatellite typing. The Galleria mellonella infection model was used to confirm in vitro resistance. We assessed the presence of ERG11 mutations, as well as the expression of ERG11 and two additional genes that contribute to antifungal resistance (CDR1 and MDR1), by using real-time quantitative PCR. All of the C. parapsilosis (sensu stricto) isolates tested exhibited fluconazole MICs between 8 and 16 MUg/ml. The in vitro data were confirmed by the failure of fluconazole in the treatment of G. mellonella infected with fluconazole-resistant strains of C. parapsilosis. Sequencing of the ERG11 gene revealed a common mutation leading to a Y132F amino acid substitution in all of the isolates, a finding consistent with their clonal origin. After fluconazole exposure, overexpression was noted for ERG11, CDR1, and MDR1 in 9/9, 9/9, and 2/9 strains, respectively. We demonstrated that a combination of molecular mechanisms, including the presence of point mutations in the ERG11 gene, overexpression of ERG11, and genes encoding efflux pumps, are involved in fluconazole resistance in C. parapsilosis. PMID- 26259796 TI - Identification of NDM-1 in a Putatively Novel Acinetobacter Species ("NB14") Closely Related to Acinetobacter pittii. AB - In this study, we describe the molecular characterization of a plasmid-located blaNDM-1 harbored by an Acinetobacter clinical isolate recovered from a patient in Turkey that putatively constitutes a novel Acinetobacter species, as shown by its distinct ARDRA (amplified 16S ribosomal DNA restriction analysis) profile and molecular sequencing techniques. blaNDM-1 was carried by a conjugative plasmid widespread among non-baumannii Acinetobacter isolates, suggesting its potential for dissemination before reaching more clinically relevant Acinetobacter species. PMID- 26259797 TI - Naegleria fowleri: pathogenesis, diagnosis, and treatment options. AB - Naegleria fowleri has generated tremendous media attention over the last 5 years due to several high-profile cases. Several of these cases were followed very closely by the general public. N. fowleri is a eukaryotic, free-living amoeba belonging to the phylum Percolozoa. Naegleria amoebae are ubiquitous in the environment, being found in soil and bodies of freshwater, and feed on bacteria found in those locations. While N. fowleri infection appears to be quite rare compared to other diseases, the clinical manifestations of primary amoebic meningoencephalitis are devastating and nearly always fatal. Due to the rarity of N. fowleri infections in humans, there are no clinical trials to date that assess the efficacy of one treatment regimen over another. Most of the information regarding medication efficacy is based on either case reports or in vitro studies. This review will discuss the pathogenesis, diagnosis, pharmacotherapy, and prevention of N. fowleri infections in humans, including a brief review of all survivor cases in North America. PMID- 26259798 TI - Preclinical Characterization and In Vivo Efficacy of GSK8853, a Small-Molecule Inhibitor of the Hepatitis C Virus NS4B Protein. AB - The hepatitis C virus (HCV) NS4B protein is an antiviral therapeutic target for which small-molecule inhibitors have not been shown to exhibit in vivo efficacy. We describe here the in vitro and in vivo antiviral activity of GSK8853, an imidazo[1,2-a]pyrimidine inhibitor that binds NS4B protein. GSK8853 was active against multiple HCV genotypes and developed in vitro resistance mutations in both genotype 1a and genotype 1b replicons localized to the region of NS4B encoding amino acids 94 to 105. A 20-day in vitro treatment of replicons with GSK8853 resulted in a 2-log drop in replicon RNA levels, with no resistance mutation breakthrough. Chimeric replicons containing NS4B sequences matching known virus isolates showed similar responses to a compound with genotype 1a sequences but altered efficacy with genotype 1b sequences, likely corresponding to the presence of known resistance polymorphs in those isolates. In vivo efficacy was tested in a humanized-mouse model of HCV infection, and the results showed a 3-log drop in viral RNA loads over a 7-day period. Analysis of the virus remaining at the end of in vivo treatment revealed resistance mutations encoding amino acid changes that had not been identified by in vitro studies, including NS4B N56I and N99H. Our findings provide an in vivo proof of concept for HCV inhibitors targeting NS4B and demonstrate both the promise and potential pitfalls of developing NS4B inhibitors. PMID- 26259799 TI - Polymyxin B in Combination with Antimicrobials Lacking In Vitro Activity versus Polymyxin B in Monotherapy in Critically Ill Patients with Acinetobacter baumannii or Pseudomonas aeruginosa Infections. AB - There is no clinical evidence supporting the use of polymyxin B in combination with another antimicrobial for infections caused by extensively drug-resistant Acinetobacter baumannii or Pseudomonas aeruginosa isolates. We developed a cohort study of patients in two intensive care units from teaching hospitals to evaluate treatment with intravenous polymyxin B for >=48 h for severe A. baumannii or P. aeruginosa infections. Covariates potentially associated with 30-day mortality were evaluated in a Cox proportional hazards model. A total of 101 patients were included; 33 (32.7%) were treated with polymyxin B in combination with an antimicrobial lacking in vitro activity and 68 (67.3%) with polymyxin B in monotherapy. The overall 30-day mortality was 59.4% (60 patients), comprising 42.4% (14 of 33) and 67.6% (46 of 68) in combination and monotherapy groups, respectively (P = 0.03). The mortality rates were 18.5/1,000 patient days and 36.4/1,000 patient days in the combination and monotherapy groups, respectively (P = 0.02). Combination therapy was independently associated with lower 30-day mortality (hazard ratio, 0.33; 95% confidence interval, 0.17 to 0.64; P = 0.001). Creatinine clearance of >=60 ml/min was also a protective factor, while a higher acute physiology and chronic health evaluation (APACHE II) score and polymicrobial infection were associated with increased mortality. The results did not change after adding a propensity score for prescribing combination therapy into the model. The protective effect remained when only combination with beta lactam or carbapenem was considered and in both subgroups of patients: those with A. baumannii infection and those with lower respiratory tract infections. To our knowledge, this is the first clinical study to show a benefit of combination over monotherapy with polymyxin B for severe extensively drug-resistant A. baumannii or P. aeruginosa infections. PMID- 26259800 TI - Constitutive and Inducible Expression of the rRNA Methylase Gene erm(B) in Campylobacter. AB - Macrolides are the antimicrobials of choice for treating human campylobacteriosis. The recent emergence of erm(B) in Campylobacter bacteria threatens the utility of this class of antibiotics. Here we report the constitutive and inducible expression of erm(B) in Campylobacter isolates derived from diarrheal patients and food-producing animals. Constitutive expression of erm(B) was associated with insertion and deletion in the regulatory region of the gene, providing the first documentation of the differential expression of erm(B) in Campylobacter bacteria. PMID- 26259802 TI - Cytotoxic triterpenoid glycosides (saikosaponins) from the roots of Bupleurum chinense. AB - As a part of our ongoing studies on cytotoxic triterpenoid saponins from herbal medicines, phytochemical investigation of the roots of Bupleurum chinense DC. afforded four new saikosaponins (1-4), along with 16 known ones (5-20). Their structures were established by direct interpretation of their spectral data, mainly HR-ESI-MS, 1D NMR and 2D NMR, and by comparison with literature data. Among them, compound 20 was isolated from the natural product for the first time. The cytotoxicities of all compounds against five selected human cancer cell lines (A549, HepG2, Hep3B, Bcap-37 and MCF-7) were assayed. In general, a number of the isolated compounds exhibited potent cytotoxic activities against the five selected human cancer cell lines. In particular, compounds 3, 8-9, 11-13, 16 and 20 showed more potent cytotoxic activities against the HepG2 and A549 cell lines than the positive control 5-fluorouracil. Based on the primary screening results, the preliminary structure-activity relationship (SAR) studies were also discussed. The SAR results suggest that the 13,28-epoxy bridge, the orientation of the hydroxyl group and the type of the sugar units are important requirements for cytotoxicity and selectivity. PMID- 26259804 TI - Tetrahydropyrrolo-diazepenones as inhibitors of ERK2 kinase. AB - A series of structure based drug design hypotheses and focused screening efforts led to the identification of tetrahydropyrrolo-diazepenones with striking potency against ERK2 kinase. The role of fluorination in mitigating microsomal clearance was systematically explored. Ultimately, it was found that fluorination of a cyclopentanol substructure provided significant improvement in both potency and human metabolic stability. PMID- 26259803 TI - Synthesis of oxygenated oleanolic and ursolic acid derivatives with anti inflammatory properties. AB - The scalable syntheses of four oxygenated triterpenes have been implemented to access substantial quantities of maslinic acid, 3-epi-maslinic acid, corosolic acid, and 3-epi-corosolic acid. Semi-syntheses proceed starting from the natural products oleanolic acid and ursolic acid. Proceeding over five steps, each of the four compounds can be synthesized on the gram scale. Divergent diastereoselective reductions of alpha-hydroxy ketones provided access to the four targeted diol containing compounds from two precursors of the oleanane or ursane lineage. These compounds were subsequently evaluated for their ability to inhibit inflammatory gene expression in a mouse model of chemically induced skin inflammation. All compounds possessed the ability to inhibit the expression of one or more inflammatory genes induced by 12-O-tetradecanoylphorbol-13 acetate in mouse skin, however, three of the compounds, corosolic acid, 3-epi-corosolic acid and maslinic acid were more effective than the others. The availability of gram quantities will allow further testing of these compounds for potential anti inflammatory activities as well as cancer chemopreventive activity. PMID- 26259805 TI - Multivalent LKgamma-PNA oligomers bind to a human telomere DNA G-rich sequence to form quadruplexes. AB - We report G-quadruplex formation between peptide nucleic acids (PNAs) composed of (L)Kgamma-PNA-G monomers and a known portion of human telomeric DNA that adopts three G3 tracts via intramolecular hydrogen bonding. The resulting complex is a bimolecular PNA-DNA heteroquadruplex. In this Letter, we show that introduction of a gamma-modification and addition of a peptide ligand does not disrupt the heteroquadruplex. Although the unmodified PNA1 forms a quadruplex with itself, the gamma-substituted PNAs (PNA2-PNA6) do not form G-quadruplexes on their own, at even high concentrations. The selectivity of these PNAs could influence the design of new quadruplex-targeting molecules or allow the quadruplex structure to be used as a scaffold for multivalent display of protein binding ligands. PMID- 26259806 TI - 2,4-Diarylamino-pyrimidines as kinase inhibitors co-targeting IGF1R and EGFR(L858R/T790M). AB - IGF1R amplification was recently implied to be related to the secondary acquired resistance against the 2nd or 3rd generation EGFR inhibitor therapies. We have successfully identified a series of 2,4-diarylamino-pyrimidines as new IGF1R/EGFR(L858R/T790M) co-targeting agents. One of the most promising compounds 8g potently inhibits both kinases with low nanomolar IC50 values, but is significantly less potent in inhibiting the wild type EGFR. The compound also displays a good kinase selectivity profile against a panel of 468 kinases. Moreover, 8g strongly suppresses the proliferation of CO-1686-resistant H1975 IGF1R cancer cells, suggesting its promising potential as a new lead compound for future anticancer drug discovery. PMID- 26259807 TI - Structure-based de novo design and synthesis of aminothiazole-based p38 MAP kinase inhibitors. AB - p38 mitogen-activated protein kinase (MAPK) is a promising target for the development of therapeutics for various immunological diseases. We designed and synthesized aminothiazole-based p38 MAPK inhibitors of with IC50 values ranging from 0.1 to 2 MUM by means of the structure-based de novo design of phenyl-(2 phenylamino-thiazol-5-yl)-methanone scaffold. Because these newly identified inhibitors were also screened for having desirable physicochemical properties as a drug candidate, they deserve consideration for further investigation as anti inflammatory drugs. Structural features relevant to the stabilization of the newly identified inhibitors in the ATP-binding site of p38 MAPK are discussed in detail. PMID- 26259808 TI - Control of Hypertension In Pregnancy Study randomised controlled trial-are the results dependent on the choice of labetalol or methyldopa? AB - OBJECTIVE: To determine whether the difference in outcomes between 'less tight' (target diastolic blood pressure [dBP] of 100 mmHg) versus 'tight' control (target dBP of 85 mmHg) in the CHIPS Trial (ISRCTN 71416914, http://pre empt.cfri.ca/;CHIPS) depended on the choice of labetalol or methyldopa, the two most commonly used antihypertensive agents in CHIPS. DESIGN: Secondary analysis of CHIPS Trial data. SETTING: International multicentre randomised controlled trial (94 sites, 15 countries). POPULATION OR SAMPLE: A total of 987 women with non-severe non-proteinuric pregnancy hypertension. METHODS: Logistic regression was used for comparisons of 'less tight' versus 'tight' control among women treated with labetalol (but not methydopa) versus methyldopa (but not labetalol). Analyses were adjusted for the influence of baseline factors, including use of any antihypertensive therapy at randomisation. MAIN OUTCOME MEASURES: Main CHIPS Trial outcomes: primary (perinatal loss or high-level neonatal care for > 48 hours), secondary (serious maternal complications), birthweight < 10th centile, severe maternal hypertension, pre-eclampsia, and delivery at < 34 or < 37 weeks. RESULTS: Of 987 women in CHIPS, antihypertensive therapy was taken by 566 women at randomisation (labetalol 111 ['less tight'] versus 127 ['tight'] or methyldopa 126 ['less tight'] versus 117 ['tight']) and 815 women after randomisation (labetalol 186 ['less tight'] versus 247 ['tight'] and methyldopa by 98 ['less tight'] versus 126 ['tight']). Following adjustment, odds ratios for outcomes in 'less tight' versus 'tight' control were similar between antihypertensive groups according to 'at randomisation' and 'after randomisation' therapy. CONCLUSION: Outcomes for 'less tight' versus 'tight' control were not dependent on use of methyldopa or labetalol. TWEETABLE ABSTRACT: In the CHIPS Trial, maternal and infant outcomes were not dependent on use of labetalol or methyldopa. PMID- 26259809 TI - A Randomized, Blinded, Controlled, Dose-Ranging Study of a Respiratory Syncytial Virus Recombinant Fusion (F) Nanoparticle Vaccine in Healthy Women of Childbearing Age. AB - BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of infant morbidity and mortality. A recombinant RSV fusion protein nanoparticle vaccine (RSV F vaccine) candidate for maternal immunization was tested for safety and immunogenicity in women of childbearing age. METHODS: Three hundred thirty women (18-35 years) were randomized to receive 1 or 2 doses of RSV F vaccine (60 or 90 ug) with or without aluminum phosphate adjuvant, or placebo at days 0 and 28. Safety was evaluated over 180 days; immunogenicity and RSV infection rates were evaluated over 112 days. RESULTS: All vaccine formulations were well tolerated, without vaccine-related serious adverse events. Anti-F immunoglobulin G antibodies rose 6.5-15.6-fold, with significantly higher levels in 2-dose, adjuvanted regimens at day 56. Palivizumab-competitive antibody levels were undetectable at day 0 but increased up to 325 ug/mL at day 56. A 2.7- and 3.5 fold rise in RSV/A and RSV/B microneutralization antibodies were noted at day 56. Between days 56 and 112, 21% (12/56) of placebo recipients and 11% of vaccinees (26/244) showed evidence of a recent RSV infection (P = .04). CONCLUSIONS: The vaccine appeared safe, immunogenic, and reduced RSV infections. Further development as a vaccine for use in maternal immunization is warranted. CLINICAL TRIALS REGISTRATION: NCT01704365. PMID- 26259810 TI - In silico structure-based design and synthesis of novel anti-RSV compounds. AB - Respiratory syncytial virus (RSV) is the major cause for respiratory tract disease in infants and young children. Currently, no licensed vaccine or a selective antiviral drug against RSV infections are available. Here, we describe a structure-based drug design approach that led to the synthesis of a novel series of zinc-ejecting compounds active against RSV replication. 30 compounds, sharing a common dithiocarbamate moiety, were designed and prepared to target the zinc finger motif of the M2-1 protein. A library of ~ 12,000 small fragments was docked to explore the area surrounding the zinc ion. Among these, seven ligands were selected and used for the preparation of the new derivatives. The results reported here may help the development of a lead compound for the treatment of RSV infections. PMID- 26259811 TI - Molecular insights into the inhibition of HIV-1 infection using a CD4 domain-1 specific monoclonal antibody. AB - An HIV-1 infection in a host cell occurs through an ordered process that involves HIV-1 attachment to the host's cellular CD4 receptor, co-receptor binding to CCR5 or CXCR4, and the subsequent fusion with the cellular membrane. The natural viral entry pathway into a host cell provides an opportunity to develop agents for the treatment of HIV-1 infections. Several engineered monoclonal antibodies specifically targeting CD4 have shown antiviral activities in clinical trials. Here, we report on an anti-CD4 mAb (15A7) that displays a unique binding specificity for domain 1 of CD4, whose epitope partially overlaps with the gp120 binding region. Moreover, 15A7 displays a much stronger binding affinity to CD4(+) cell lines after HIV infection. 15A7 is able to block and neutralize a broad range of primary HIV-1 isolates and T cell-line passage strains. Notably, the bivalent F(ab')2 form of 15A7 is more effective than the Fab form in blocking HIV-1 infection, which is further supported by molecular docking analyses. Together, these results suggest that this novel antibody may exert its antiviral activity by blocking gp120 targeting to the CD4 receptor or competing with gp120 for CD4 receptor binding and might present post-attachment neutralization activity. This antibody could provide a new candidate to efficiently block HIV-1 infection or provide new starting materials for HIV treatment, especially when HIV-1-resistant strains against the current CD4 mAb treatments have already been identified. PMID- 26259812 TI - Synthetic pregnenolone derivatives as antiviral agents against acyclovir resistant isolates of Herpes Simplex Virus Type 1. AB - The conventional therapy for the management of Herpes Simplex Virus Type 1 (HSV 1) infections mainly comprises acyclovir (ACV) and other nucleoside analogues. A common outcome of this treatment is the emergence of resistant viral strains, principally when immunosuppressed patients are involved. Thus, the development of new antiherpetic compounds remains as a central challenge. In this work we describe the synthesis and the in vitro antiherpetic activity of a new family of steroidal compounds derived from the endogenous hormone pregnenolone. Some of these derivatives showed a remarkable inhibitory effect on HSV-1 spread both on wild type and ACV-resistant strains. The results also show that these compounds seem to interfere with the late steps of the viral cycle. PMID- 26259813 TI - Comparative Genomic Analysis of Meningitis- and Bacteremia-Causing Pneumococci Identifies a Common Core Genome. AB - Streptococcus pneumoniae is a nasopharyngeal commensal that occasionally invades normally sterile sites to cause bloodstream infection and meningitis. Although the pneumococcal population structure and evolutionary genetics are well defined, it is not clear whether pneumococci that cause meningitis are genetically distinct from those that do not. Here, we used whole-genome sequencing of 140 isolates of S. pneumoniae recovered from bloodstream infection (n = 70) and meningitis (n = 70) to compare their genetic contents. By fitting a double exponential decaying-function model, we show that these isolates share a core of 1,427 genes (95% confidence interval [CI], 1,425 to 1,435 genes) and that there is no difference in the core genome or accessory gene content from these disease manifestations. Gene presence/absence alone therefore does not explain the virulence behavior of pneumococci that reach the meninges. Our analysis, however, supports the requirement of a range of previously described virulence factors and vaccine candidates for both meningitis- and bacteremia-causing pneumococci. This high-resolution view suggests that, despite considerable competency for genetic exchange, all pneumococci are under considerable pressure to retain key components advantageous for colonization and transmission and that these components are essential for access to and survival in sterile sites. PMID- 26259814 TI - Primary Structural Variation in Anaplasma marginale Msp2 Efficiently Generates Immune Escape Variants. AB - Antigenic variation allows microbial pathogens to evade immune clearance and establish persistent infection. Anaplasma marginale utilizes gene conversion of a repertoire of silent msp2 alleles into a single active expression site to encode unique Msp2 variants. As the genomic complement of msp2 alleles alone is insufficient to generate the number of variants required for persistence, A. marginale uses segmental gene conversion, in which oligonucleotide segments from multiple alleles are recombined into the expression site to generate a novel msp2 mosaic not represented elsewhere in the genome. Whether these segmental changes are sufficient to evade a broad antibody response is unknown. We addressed this question by identifying Msp2 variants that differed in primary structure within the immunogenic hypervariable region microdomains and tested whether they represented true antigenic variants. The minimal primary structural difference between variants was a single amino acid resulting from a codon insertion, and overall, the amino acid identity among paired microdomains ranged from 18 to 92%. Collectively, 89% of the expressed structural variants were also antigenic variants across all biological replicates, independent of a specific host major histocompatibility complex haplotype. Biological relevance is supported by the following: (i) all structural variants were expressed during infection of a natural host, (ii) the structural variation observed in the microdomains corresponded to the mean length of variants generated by segmental gene conversion, and (iii) antigenic variants were identified using a broad antibody response that developed during infection of a natural host. The findings demonstrate that segmental gene conversion efficiently generates Msp2 antigenic variants. PMID- 26259816 TI - Effects of fish cues on mosquito larvae development. AB - We investigated the effects of predator-released kairomones on life history traits of larval Culex pipiens (Linnaeus). We compared the development time and survival of sibling larvae, reared in either water conditioned by the presence of Gambusia affinis (Baird and Girard) or fishless control-water. Our results indicate that larvae developing in fish-conditioned water (FCW) pupated faster than larvae in fishless-control water. The effect of FCW on larval survival was evident only in females. Surprisingly, FCW increased female survival. In both development-time and survival, boiling the water eliminated the FCW effect, supporting our hypothesis that fish conditioning is based on kairomones. Accelerated metamorphosis in response to predator released kairomones, evident in our results, is a rarely described phenomenon. Intuitively, when exposed to predator associated signals, aquatic larvae should metamorphose earlier to escape the higher risk of predation. However, theoretical models predict this outcome only under specific conditions. Indeed, longer - rather than shorter - time to metamorphosis is usually observed in response to predation risk. We argue that the response of larval mosquitoes to predation risk is context-dependent. Shortening larval development time may not be an exceptional response, but rather represents a part of a response spectrum that depends on the level of predation risk and resource abundance. PMID- 26259815 TI - Coculture of Escherichia coli O157:H7 with a Nonpathogenic E. coli Strain Increases Toxin Production and Virulence in a Germfree Mouse Model. AB - Escherichia coli O157:H7 is a notorious foodborne pathogen due to its low infectious dose and the disease symptoms it causes, which include bloody diarrhea and severe abdominal cramps. In some cases, the disease progresses to hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS), due to the expression of one or more Shiga toxins (Stx). Isoforms of Stx, including Stx2a, are encoded within temperate prophages. In the presence of certain antibiotics, phage induction occurs, which also increases the expression of toxin genes. Additionally, increased Stx2 accumulation has been reported when O157:H7 was cocultured with phage-susceptible nonpathogenic E. coli. This study characterized an E. coli O157:H7 strain, designated PA2, that belongs to the hypervirulent clade 8 cluster. Stx2a levels after ciprofloxacin induction were lower for PA2 than for the prototypical outbreak strains Sakai and EDL933. However, during coculture with the nonpathogenic strain E. coli C600, PA2 produced Stx2a levels that were 2 to 12-fold higher than those observed during coculture with EDL933 and Sakai, respectively. Germfree mice cocolonized by PA2 and C600 showed greater kidney damage, increased Stx2a accumulation in feces, and more visible signs of disease than mice given PA2 or C600 alone. These data suggest one mechanism by which microorganisms associated with the colonic microbiota could enhance the virulence of E. coli O157:H7, particularly a subset of clade 8 strains. PMID- 26259817 TI - Diversity and abundance of mosquitoes (Diptera:Culicidae) in an urban park: larval habitats and temporal variation. AB - Urban parks are areas designated for human recreation but also serve as shelter and refuge for populations of several species of native fauna, both migratory and introduced. In Brazil, the effect of annual climate variations on Aedes aegypti and dengue epidemics in large cities like Sao Paulo is well known, but little is known about how such variations can affect the diversity of mosquito vectors in urban parks and the risk of disease transmission by these vectors. This study investigates the influence of larval habitats and seasonal factors on the diversity and abundance of Culicidae fauna in Anhanguera Park, one of the largest remaining green areas in the city of Sao Paulo. Species composition and richness and larval habitats were identified. Seasonality (cold-dry and hot-rainy periods) and year were considered as explanatory variables and the models selection approach was developed to investigate the relationship of these variables with mosquito diversity and abundance. A total of 11,036 specimens from 57 taxa distributed in 13 genera were collected. Culex nigripalpus, Cx. quinquefasciatus and Aedes albopictus were the most abundant species. Bamboo internodes and artificial breeding sites showed higher abundance, while ponds and puddles showed greater richness. Significant relationships were observed between abundance and seasonality, with a notable increase in the mosquitos abundance in the warm-rainy periods. The Shannon and Berger-Parker indices were related with interaction between seasonality and year, however separately these predictors showed no relationship with ones. The increased abundance of mosquitoes in warm-rainy months and the fact that some of the species are epidemiologically important increase not only the risk of pathogen transmission to people who frequent urban parks but also the nuisance represented by insect bites. The findings of this study highlight the importance of knowledge of culicid ecology in green areas in urban environments. PMID- 26259818 TI - Caregivers' treatment-seeking behaviors and practices in Uganda-A systematic review (Part II). AB - Prompt treatment with artemisinin combination therapies (ACTs) remains the cornerstone for managing uncomplicated malaria caused by Plasmodium falciparum. In accordance with global initiatives to curb malaria, the Ugandan government pledged to increase the proportion of children under five to receive the first line antimalarial treatment to 85% by 2010. To achieve this, Uganda has implemented several initiatives to improve prompt access to ACTs. While several studies have evaluated various aspects of caregivers' treatment-seeking and its impact on malaria management in children since the advent of ACT, this is the first systematic review to synthesize the Uganda literature since 2004. A comprehensive search employed key web search engines databases. A total of 19 studies met the inclusion criteria. This review found that although most Ugandans associate mosquitoes with malaria, misconceptions about the cause of malaria is common. Home management continues to be a common first response, with most caregivers seeking subsequent treatment if the child does not improve. A major concern arising from this review was that an increase in ACT knowledge does not always translate into a child receiving an ACT. While 84% of caregivers in a recent national study spontaneously named ACT as the antimalarial of choice, only half of the children were reported to have received an antimalarial and only 44% received an ACT. As with ACT usage, prompt use of ACT fell significantly short of the 2010 target. Given the on-going popularity of home management, future research is needed to examine the diversity and adequacy of home management for malaria and the sequence of care provided from the moment of recognition of initial symptoms. Considering the pervasive use of polypharmacy to manage malaria, further research is needed to quantify the proportion of children who receive an appropriate antimalarial - defined as receiving only the first-line treatment. Finally, given children's reliance on caregivers to seek out appropriate care on their behalf, future studies need to examine specific assets and challenges influencing caregivers' treatment-seeking behaviors in order to positively influence decision-making at the household level. PMID- 26259821 TI - Comparison of bacterial community structure and dynamics during the thermophilic composting of different types of solid wastes: anaerobic digestion residue, pig manure and chicken manure. PMID- 26259819 TI - Fluorescent ratiometric pH indicator SypHer2: Applications in neuroscience and regenerative biology. AB - BACKGROUND: SypHer is a genetically encoded fluorescent pH-indicator with a ratiometric readout, suitable for measuring fast intracellular pH shifts. However, the relatively low brightness of the indicator limits its use. METHODS: Here we designed a new version of pH-sensor called SypHer-2, which has up to three times brighter fluorescence in cultured mammalian cells compared to the SypHer. RESULTS: Using the new indicator we registered activity-associated pH oscillations in neuronal cell culture. We observed prominent transient neuronal cytoplasm acidification that occurs in parallel with calcium entry. Furthermore, we monitored pH in presynaptic and postsynaptic termini by targeting SypHer-2 directly to these compartments and revealed marked differences in pH dynamics between synaptic boutons and dendritic spines. Finally, we were able to reveal for the first time the intracellular pH drop that occurs within an extended region of the amputated tail of the Xenopus laevis tadpole before it begins to regenerate. CONCLUSIONS: SypHer2 is suitable for quantitative monitoring of pH in biological systems of different scales, from small cellular subcompartments to animal tissues in vivo. GENERAL SIGNIFICANCE: The new pH-sensor will help to investigate pH-dependent processes in both in vitro and in vivo studies. PMID- 26259820 TI - Identification of an RNA element for specific coordination of A-to-I RNA editing on HTR2C pre-mRNA. AB - Adenosine-to-Inosine (A-to-I) RNA editing is an intracellular mechanism in which inosine is specifically substituted against adenosine by the action of adenosine deaminases acting on RNA (ADARs). Serotonin 2C receptor (HTR2C) is encoded through combinatorial A-to-I RNA editing at recoding sites (A - E site) on its pre-mRNA. Although the efficiency of RNA editing at particular sites is known to be critical for modulating the serotonin signaling, the mechanistic details of site-specific editing on HTR2C pre-mRNA are not fully understood. Toward complete understanding of this mechanism, we discovered an RNA element, which coordinates site-specific RNA editing on HTR2C pre-mRNA by an in vitro editing assay and secondary structural analysis of mutant HTR2C RNA fragments. Our results showed that HTR2C pre-mRNA forms a characteristic structure, which was restricted by the internal loop and Watson-Crick base-pair interaction on site E, for intrinsic editing. We suggest that the internal loop would contribute toward adjusting the relative distance and/or geometry between the editing sites and the scaffold for ADAR. PMID- 26259822 TI - Controlled intracellular generation of reactive oxygen species in human mesenchymal stem cells using porphyrin conjugated nanoparticles. AB - Nanoparticles capable of generating controlled amounts of intracellular reactive oxygen species (ROS), that advance the study of oxidative stress and cellular communication, were synthesized by functionalizing polyacrylamide nanoparticles with zinc(II) porphyrin photosensitisers. Controlled ROS production was demonstrated in human mesenchymal stem cells (hMSCs) through (1) production of nanoparticles functionalized with varying percentages of Zn(II) porphyrin and (2) modulating the number of doses of excitation light to internalized nanoparticles. hMSCs challenged with nanoparticles functionalized with increasing percentages of Zn(II) porphyrin and high numbers of irradiations of excitation light were found to generate greater amounts of ROS. A novel dye, which is transformed into fluorescent 7-hydroxy-4-trifluoromethyl-coumarin in the presence of hydrogen peroxide, provided an indirect indicator for cumulative ROS production. The mitochondrial membrane potential was monitored to investigate the destructive effect of increased intracellular ROS production. Flow cytometric analysis of nanoparticle treated hMSCs suggested irradiation with excitation light signalled controlled apoptotic cell death, rather than uncontrolled necrotic cell death. Increased intracellular ROS production did not induce phenotypic changes in hMSC subcultures. PMID- 26259823 TI - Whole-genome analysis of Azoarcus sp. strain CIB provides genetic insights to its different lifestyles and predicts novel metabolic features. AB - The genomic features of Azoarcus sp. CIB reflect its most distinguishing phenotypes as a diazotroph, facultative anaerobe, capable of degrading either aerobically and/or anaerobically a wide range of aromatic compounds, including some toxic hydrocarbons such as toluene and m-xylene, as well as its endophytic lifestyle. The analyses of its genome have expanded the catabolic potential of strain CIB toward common natural compounds, such as certain diterpenes, that were not anticipated as carbon sources. The high number of predicted solvent efflux pumps and heavy metal resistance gene clusters has provided the first evidence for two environmentally relevant features of this bacterium that remained unknown. Genome mining has revealed several gene clusters likely involved in the endophytic lifestyle of strain CIB, opening the door to the molecular characterization of some plant growth promoting traits. Horizontal gene transfer and mobile genetic elements appear to have played a major role as a mechanism of adaptation of this bacterium to different lifestyles. This work paves the way for a systems biology-based understanding of the abilities of Azoarcus sp. CIB to integrate aerobic and anaerobic metabolism of aromatic compounds, tolerate stress conditions, and interact with plants as an endophyte of great potential for phytostimulation and phytoremediation strategies. Comparative genomics provides an Azoarcus pan genome that confirms the global metabolic flexibility of this genus, and suggests that its phylogeny should be revisited. PMID- 26259824 TI - Allogeneic mesenchymal stem cells inhibited T follicular helper cell generation in rheumatoid arthritis. AB - T follicular helper (Tfh) cells provide help for antigen-specific B cells. We have previously shown that Tfh cell frequency was increased and associated with auto-antibodies in patients with rheumatoid arthritis (RA), suggesting a possible involvement of Tfh cells in its pathogenesis. Mesenchymal stem cells (MSCs) represent a promising alternative cell therapy for RA by modulating T and B cell activation and proliferation. However, it remains unknown whether MSCs have immunoregulation on Tfh cells. In this paper, we have demonstrated that allogeneic MSCs could suppress Tfh cell differentiation in RA patients partly via the production of indoleamine 2,3-dioxygenase (IDO). IFNgamma generated from Tfh cell differentiation system induced IDO expression on MSCs. MSCs transplantation (MSCT) into collagen-induced arthritis (CIA) mice prevented arthritis progression by inhibiting both the number and function of Tfh cells in vivo. These findings reveal a novel suppressive function of MSCs in Tfh cells, which has implication in understanding the underlying mechanisms of the immunotherapeutic effects of MSCs on RA patients. PMID- 26259825 TI - Refining the pathway of carbide insertion into the nitrogenase M-cluster. AB - Carbide insertion plays a pivotal role in the biosynthesis of M-cluster, the cofactor of nitrogenase. Previously, we proposed a carbide insertion pathway involving methyltransfer from SAM to a FeS precursor and hydrogen abstraction from this methyl group that initiates the radical-based precursor maturation. Here we demonstrate that the methyl group is transferred to a precursor associated sulfur before hydrogen abstraction, thereby refining the initial steps of the carbide insertion pathway. PMID- 26259826 TI - The reliability, validity, sensitivity, specificity and predictive values of the Chinese version of the Rowland Universal Dementia Assessment Scale. AB - AIMS AND OBJECTIVES: The purpose of this study was to translate the Rowland Universal Dementia Assessment Scale into Chinese and to evaluate the psychometric properties (reliability and validity) and the diagnostic properties (sensitivity, specificity and predictive values) of the Chinese version of the Rowland Universal Dementia Assessment Scale. BACKGROUND: The accurate detection of early dementia requires screening tools with favourable cross-cultural linguistic and appropriate sensitivity, specificity, and predictive values, particularly for Chinese-speaking populations. DESIGN: This was a cross-sectional, descriptive study. METHODS: Overall, 130 participants suspected to have cognitive impairment were enrolled in the study. A test-retest for determining reliability was scheduled four weeks after the initial test. Content validity was determined by five experts, whereas construct validity was established by using contrasted group technique. The participants' clinical diagnoses were used as the standard in calculating the sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: The study revealed that the Chinese version of the Rowland Universal Dementia Assessment Scale exhibited a test-retest reliability of 0.90, an internal consistency reliability of 0.71, an inter-rater reliability (kappa value) of 0.88 and a content validity index of 0.97. Both the patients and healthy contrast group exhibited significant differences in their cognitive ability. The optimal cut-off points for the Chinese version of the Rowland Universal Dementia Assessment Scale in the test for mild cognitive impairment and dementia were 24 and 22, respectively; moreover, for these two conditions, the sensitivities of the scale were 0.79 and 0.76, the specificities were 0.91 and 0.81, the areas under the curve were 0.85 and 0.78, the positive predictive values were 0.99 and 0.83 and the negative predictive values were 0.96 and 0.91 respectively. CONCLUSION: The Chinese version of the Rowland Universal Dementia Assessment Scale exhibited sound reliability, validity, sensitivity, specificity and predictive values. RELEVANCE TO CLINICAL PRACTICE: This scale can help clinical staff members to quickly and accurately diagnose cognitive impairment and provide appropriate treatment as early as possible. PMID- 26259827 TI - Tph2 gene deletion enhances amphetamine-induced hypermotility: effect of 5-HT restoration and role of striatal noradrenaline release. AB - Variants of tryptophan hydroxylase-2 (Tph2), the gene encoding enzyme responsible for the synthesis of brain serotonin (5-HT), have been associated with neuropsychiatric disorders, substance abuse and addiction. This study assessed the effect of Tph2 gene deletion on motor behavior and found that motor activity induced by 2.5 and 5 mg/kg amphetamine was enhanced in Tph2(-/-) mice. Using the in vivo microdialysis technique we found that the ability of amphetamine to stimulate noradrenaline (NA) release in the striatum was reduced by about 50% in Tph2(-/-) mice while the release of dopamine (DA) was not affected. Tph2 deletion did not affect the release of NA and DA in the prefrontal cortex. The role of endogenous 5-HT in enhancing the effect of amphetamine was confirmed showing that treatment with the 5-HT precursor 5-hydroxytryptophan (10 mg/kg) restored tissue and extracellular levels of brain 5-HT and the effects of amphetamine on striatal NA release and motor activity in Tph2(-/-) mice. Treatment with the NA precursor dihydroxyphenylserine (400 mg/kg) was sufficient to restore the effect of amphetamine on striatal NA release and motor activity in Tph2(-/-) mice. These findings indicate that amphetamine-induced hyperactivity is attenuated by endogenous 5-HT through the inhibition of striatal NA release. Tph2(-/-) mice may be a useful preclinical model to assess the role of 5-HT-dependent mechanisms in the action of psychostimulants. Acute sensitivity to the motor effects of amphetamine has been associated to increased risk of psychostimulant abuse. Here, we show that deletion of Tph2, the gene responsible for brain 5-HT synthesis, enhances the motor effect of amphetamine in mice through the inhibition of striatal NA release. This suggests that Tph2(-/-) mice is a useful preclinical model to assess the role of 5-HT-dependent mechanisms in psychostimulants action. Tph2, tryptophan hydroxylase-2. PMID- 26259829 TI - Detection of Traces of Ovalbumin and Casein in White and Red Wines by Quantitative Western Blotting. AB - Fining of wine with agents containing cow's milk or hen's egg white is a common and traditional procedure. In light of increasing food allergies all over the world, the presence of fining residues has been subject of intense debate. Switzerland does not make exception, and since 2009 the Federal Department of Home Affairs has modified its food regulations stating that the labels must show if traces of fining agents are present. Nevertheless, the application of this regulation is not based on an official analytical method. In this study we show that immunoblotting is an efficient technique to detect and quantify ovalbumin and casein residues in bottled wine. We showed that final filtration is an essential step to remove finings in red wine, and that overfining of white wine may result in fining residues in finished products. Finally, for the first time in Switzerland, 22 samples were taken by food safety inspectors and officially analyzed for the regional food control authority of the Canton of Vaud. These samples were allergen free, but a larger study is currently planned in collaboration with other regional authorities of Switzerland to complete these results and make a complete picture of the Swiss wine production. PMID- 26259828 TI - miR-744 enhances type I interferon signaling pathway by targeting PTP1B in primary human renal mesangial cells. AB - Renal mesangial cells (RMCs) constitute a population of cells in glomerular mesangium. Inflammatory cytokines produced by RMCs play a vital role in renal inflammation. miRNAs are key regulators of inflammatory cytokine expression. The abnormal expression of renal miRNAs and the consequent changes in inflammatory signal transduction are closely associated with renal inflammation. However, our knowledge of the functions of renal miRNAs is still limited. In this study, we investigated the role of miR-744 in type I interferon (IFN) signaling pathway in primary human RMCs. We show that overexpression of miR-744 enhances IFN-induced CCL2, CCL5, CXCL10, and IL6 expression specifically in RMCs. We found that the activation of TYK2, STAT1 and STAT3 was significantly enhanced by miR-744. miR 744 also enhanced the activation of non-classical signal components, such as ERK and p38. We then identified PTP1B, a ubiquitously expressed phosphatase, as the target of miR-744 that is responsible for enhancing type I IFN response. Finally, miR-744 expression was induced by type I IFN in RMCs. Collectively, our data indicate that by targeting PTP1B, miR-744 plays a feed-forward role in regulating type I IFN signaling pathway. These findings give us new insights into the functions of renal miRNAs in regulating important signaling pathways. PMID- 26259830 TI - Monosialoteterahexosyl ganglioside induces the differentiation of human umbilical cord-derived mesenchymal stem cells into neuron-like cells. AB - In the present study, human umbilical cord-derived mesenchymal stem cells (hUMSCs) were investigated for their potential to be induced to differentiate in vitro into neuron-like cells by monosialoteterahexosyl ganglioside (GM1). Mononuclear cells obtained from umbilical cords from women with full-term pregnancies whose babies were delivered by cesarean section were cultivated in vitro and their surface antigen expression profiles were monitored. Following amplification, the cells were divided into 5 groups, of which 4 (groups A-D) were treated with GM1 at doses of 50, 100, 150 and 200 ug/ml, respectively. The control (group E) was treated with the vehicle only. The ability of GM1 to induce the differentiation of the hUMSCs into neuron-like cells was monitored for 6 h. The expression levels of microtubule-associated protein-2 (MAP-2), neurofilament protein (NF-H) and glial fibrillary acidic protein (GFAP) were measured by immunohistochemistry. Following exposure to GM1, the hUMSCs first appeared to have a diamond or polygonal shape and gradually grew into long spindle-shaped cells, finally exhibiting a radiating or swirling pattern. The cells maintained a strong proliferative capacity after continuous passage. Flow cytometry revealed that the hUMSCs expressed CD73, CD90 and CD105 up to passage 10, but not CD11b, CD19, CD34, CD45 or HLA-DR. Treatment with GM1 for 6 h led to the appearance of neuron-like cells with oval-shaped cell bodies and protruding neurites. These neuron-like cells were positive for MAP-2 and NF-H, but negative for GFAP expression. No changes in the expression of these markers were observed in the control group. Thus, the findings of the present study demonstrate that GM1 effectively induces hUMSCs to differentiate into neuron-like cells. PMID- 26259831 TI - The complete nucleotide sequence and genome organization of lychnis mottle virus. AB - The complete genomic sequence of lychnis mottle virus (LycMoV) from a Lychnis cognata plant was determined. LycMoV has a bipartite genome consisting of RNA1 (7,428 nt) and RNA2 (3,734 nt). Species in the family Secoviridae are demarcated based on their amino acid similarities in the protease-polymerase and coat protein. In LycMoV, these proteins share 90% and 63% sequence similarity, respectively, with the most closely related virus, strawberry latent ringspot virus, which is a member of the family Secoviridae but has not been assigned to a genus. Therefore, LycMoV is a tentative new virus of the family Secoviridae. PMID- 26259832 TI - How phosphoubiquitin activates Parkin. AB - A recent report, solving the structure of a Parkin-phosphoubiquitin complex, greatly advances the understanding of the Parkin activation mechanism. PMID- 26259833 TI - Factors associated with breast milk intake among 9-10-month-old Malawian infants. AB - Exclusive breastfeeding is recommended during the first 6 months of life; thereafter, continued breastfeeding along with nutritious complementary foods is recommended. Continued breastfeeding contributes a substantial proportion of nutrient needs and promotes healthy growth and development, but the quantity of breast milk consumed may be highly variable and little is known about the factors associated with breast milk intake after 6 months of age. The present study was conducted to assess factors associated with breast milk intake of Malawian infants at 9-10 months of age. Breast milk intake was measured using the dose-to mother deuterium oxide dilution method in a subsample of 358 Malawian infants who were participating in a randomized controlled trial of lipid-based nutrient supplements. Regression analysis was used to assess associations between breast milk intake and several maternal and infant variables. Mean (standard deviation) breast milk intake was 752 (244) g day(-1) . In multiple regression, breast milk intake was positively associated with infant weight (+62 g per kg body weight, P < 0.01) and maternal height (P < 0.01) and negatively associated with maternal education and age (P < 0.01). There was a non-significant (P = 0.063) inverse association between energy from non-breast milk sources and breast milk intake. In this rural Malawian population, infant weight is the main predictor of breast milk intake, even after the first 6 months of life. PMID- 26259834 TI - Determination of iron in drinking water after its flotation concentration by two new dithiocarbamate collectors. AB - Two new methods for the determination of iron by atomic absorption spectrometry (AAS) are proposed for drinking water. The determination was made after flotation concentration of Fe by using of two new flotation collectors: lead(II) heptyldithiocarbamate, Pb(HpDTC)2 and cobalt(III) heptyldithiocarbamate Co(HpDTC)3. All important parameters for the two proposed procedures were optimised (pH, mass of Pb, mass of Co, amount of HpDTC(-), type of surfactant, induction time, etc.). Flotation recovery (R) of Fe was very high (from 94.4 to 104.4%) for the two proposed procedures. The detection limit of the methods was 2.17 MUg L(-1) for Pb(HpDTC)2 and 2.39 MUg L(-1) for Co(HpDTC)3, respectively. The proposed methods have been applied for the analysis of five samples of drinking water. The acquired AAS results for Fe by both new methods were compared with those obtained by inductively coupled plasma-atomic emission spectrometry (AES-ICP). It is shown that they are in good agreement. The results are also confirmed by the method of standard additions. PMID- 26259835 TI - Classifying communication ability in cerebral palsy. PMID- 26259836 TI - An in-depth assessment of India's Mother and Child Tracking System (MCTS) in Rajasthan and Uttar Pradesh. AB - BACKGROUND: India's Mother and Child Tracking System (MCTS)(1) is an information system for tracking maternal and child health beneficiaries in India's public health system, and improving service delivery planning and outcomes. This ambitious project was launched in 2009 and currently covers all states in India, but no in-depth assessment of the system has been conducted. This study by the Public Health Foundation of India (PHFI) evaluated the performance of MCTS and identified implementation challenges in areas in Rajasthan and Uttar Pradesh (UP) in December 2012. METHODS: Two assessment methods were employed: a Data Quality Assessment (DQA) to evaluate data quality and an assessment survey to identify implementation challenges. The survey comprised semi-structured questionnaires for health staff in the sampled districts, observation checklists and survey investigator notes. Purposive sampling was used for selecting two districts in each state and two blocks in each district. For the DQA, 45 mothers who became pregnant and 84 children born within the stipulated timeframes were randomly sampled. RESULTS: DQA overall performance numbers were 34% for pregnant women and 33% for children in the Rajasthan study areas, while UP's performance numbers were 18% for pregnant women and 25% for children. Weaknesses in the MCTS' data completeness accounted for much of this performance shortfall. The beneficiary profiles for Rajasthan were largely incomplete, and the MCTS in UP struggled to register beneficiaries. Shared challenges in both states were the absence of clear processes and guidelines governing data processes, and the lack of systematic monitoring and supervision frameworks for MCTS implementation. As a result, Front Line Health Workers (FHWs) were overburdened with data documentation work, and there were long delays in data capturing. FHWs and block level health officials were not adequately trained in using the MCTS. UP staff reported unreliable internet and electricity availability, lack of dedicated data entry personnel, and a shortage of consumables such as MCTS registers. CONCLUSIONS: There is an urgent need to create data processes and supervision guidelines that complement existing workflows and service delivery priorities. Health staff should be trained to implement these guidelines. MCTS outputs, such as service delivery planning tools, should replace existing tools once data quality improves. PMID- 26259837 TI - Monomeric and dimeric 9-O anthraquinone and phenanthryl derivatives of cinchona alkaloids as chiral solvating agents for the NMR enantiodiscrimination of chiral hemiesters. AB - Mono- and bis-alkaloid chiral auxiliaries with anthraquinone or phenanthryl cores were probed as chiral solvating agents (CSAs) for the enantiodiscrimination of chiral cyclic hemiesters. The dimeric anthraquinone derivative and the monomeric phenanthryl one showed remarkable efficiency in the nuclear magnetic resonance (NMR) differentiation of enantiomeric mixtures of hemiesters. An anthraquinone analogous with a single alkaloid unit was remarkably less effective. The conformational prevalence of the chiral auxiliaries were ascertained by NMR. PMID- 26259838 TI - Physical function continues to improve when clinical remission is sustained in rheumatoid arthritis patients. AB - INTRODUCTION: To investigate the course of functional status assessed by health assessment questionnaire (HAQ) in rheumatoid arthritis (RA) patients with sustained clinical remission (REM). METHODS: In recent RA clinical trials, we identified patients with subsequent visits of >=24 weeks in clinical REM according to the disease activity score using 28-joint counts including C reactive protein (DAS28) (<=2.6), or simplified disease activity index (SDAI) (<=3.3). Area under the curve (AUC) and mean HAQ scores throughout the time in sustained REM were compared using t test, analyses of variance (ANOVA) and adjusted general linear modeling (GLM) with repeated measures. In Cox regression analyses, the time to regain full physical function was modeled. Sensitivity analyses were performed in patients of sustained SDAI low disease activity (LDA; SDAI <=11). RESULTS: A total of 610 out of 4364 patients achieved sustained DAS28 REM (14%) and 252 SDAI REM (5.8%). ANOVA testing for linear trend showed significant decrease of mean HAQ from week 0 (start of REM) to week 24, regardless of REM criteria used. AUC of HAQ throughout 24 weeks of REM was higher in DAS28 compared to SDAI REM (p <=0.01). GLM adjusting for covariates showed significant decrease of monthly HAQ scores from week 0 to 24 (DAS28: 0.276, 0.243, 0.229, 0.222, 0.219, 0.209 to 0.199; p = 0.0001; SDAI: 0.147, 0.142, 0.149, 0.129, 0.123, 0.117 to 0.114; p = 0.029). Similarly, a decrease of HAQ over time was found in patients of sustained SDAI LDA. In DAS28 REM, the chance of regaining full physical function was higher for female (hazard ratio HR [95% confidence interval]: 1.41 [1.13-1.76]) and early RA patients (disease duration <=2 years: HR 1.29 [1.01-1.65]); in SDAI REM no significant differences were found. CONCLUSIONS: Physical function continues to improve if the target of REM or LDA is sustained. The stringency of the remission criteria determines achievement of the best possible functional improvement. PMID- 26259839 TI - Therapeutic assessment of chloroquine-primaquine combined regimen in adult cohort of Plasmodium vivax malaria from a tertiary care hospital in southwestern India. AB - BACKGROUND: Of late there have been accounts of therapeutic failure and chloroquine resistance in Plasmodium vivax malaria especially from Southeast Asian regions. The present study was conducted to assess the therapeutic efficacy of chloroquine-primaquine (CQ-PQ) combined regimen in a cohort of uncomplicated P. vivax mono-infection. METHODS: A tertiary care hospital-based prospective study was conducted among adult cohort with mono-infection P. vivax malaria as per the World Health Organization's protocol of in vivo assessment of anti malarial therapeutic efficacy. Participants were treated with CQ 25 mg/kg body weight divided over 3 days and PQ 0.25 mg/kg body weight daily for 2 weeks. RESULTS: Of a total of 125 participants recruited, 122 (97.6%) completed day 28 follow up, three (2.4%) participants were lost to follow-up. Eight patients (6.4%) were ascertained to have mixed P. vivax and Plasmodium falciparum infection by nested polymerase chain reaction test. The majority of subjects (56.8%, 71/125) became aparasitaemic on day 2 followed by 35.2% (44/125) on day 3, and 8% (10/125) on day 7, and remained so thereafter. Overall only one therapeutic failure (0.8%, 1/125) occurred on day 3 due to persistence of fever and parasitaemia. CONCLUSIONS: CQ-PQ combined regimen remains outstandingly effective for uncomplicated P. vivax malaria and should be retained as treatment of choice in the study region. One case of treatment failure indicates possible resistance which warrants constant vigilance and periodic surveillance. PMID- 26259840 TI - Multicentre prospective clinical application of the T14 paediatric outcome tool. AB - OBJECTIVE: This study aimed to measure changes in disease-specific quality of life in children following tonsillectomy or adenotonsillectomy. METHODS: A multicentre prospective cohort study was performed involving seven ENT departments in England. A total of 276 children entered the study over a 2-month period: 107 underwent tonsillectomy and 128 adenotonsillectomy. Forty-one children referred with throat problems initially managed by watchful waiting were also recruited. The follow-up period was 12 months. Outcome measures were the T14, parental impressions of their child's quality of life and the number of days absent from school. RESULTS: One-year follow-up data were obtained from 150 patients (52 per cent). The mean baseline T14 score in the non-surgical group was significantly lower (T14 = 23) than in the tonsillectomy group (T14 = 31) or the adenotonsillectomy group (T14 = 35; p < 0.001). There was a significant improvement in the T14 scores of responders in all groups at follow up. The effect size was 1.3 standard deviations (SD) for the non-surgical group, 2.1 SD for the tonsillectomy group and 1.9 SD for the adenotonsillectomy group. Between group differences did not reach statistical significance. A third of children in the non-surgical group underwent surgery during the follow-up period. CONCLUSION: Children who underwent surgical intervention achieved a significant improvement in disease-specific quality of life. Less severely affected children were managed conservatively and also improved over 12 months, but 1 in 3 crossed over to surgical intervention. PMID- 26259841 TI - rApi m 3 and rApi m 10 improve detection of honey bee sensitization in Hymenoptera venom-allergic patients with double sensitization to honey bee and yellow jacket venom. AB - Recombinant allergens improve the diagnostic precision in Hymenoptera venom allergy (HVA), in particular in patients with double sensitization to both honey bee (HBV) and yellow jacket venom (YJV). While currently available vespid allergens allow the detection of >95% of YJV-allergic patients, the sensitization frequency to the only available HBV marker allergen rApi m 1 in HBV-allergic patients is lower. Here, we demonstrate that sIgE to additional HBV marker allergens rApi m 3 and rApi m 10 allows the detection of genuine HBV sensitization in 46-65% of Api m 1 negative sera. This is of particular relevance in patients with double sensitization to HBV and YJV that did not identify the culprit insect. Addition of sIgE to rApi m 3 and rApi m 10 provides evidence of HBV sensitization in a large proportion of rApi m 1-negative patients and thus provides a diagnostic marker and rationale for VIT treatment with HBV, which otherwise would have been missing. PMID- 26259842 TI - New Highly Active Antiretroviral drugs and generic drugs for the treatment of HIV infection: a budget impact analysis on the Italian National Health Service (Lombardy Region, Northern Italy). AB - BACKGROUND: In the healthcare sector, it is crucial to identify sustainable strategies in order to allow the introduction and use of innovative technologies. Now, and over the next few years, the expiry of patents for different antiretroviral drugs offers an opportunity to increase the efficiency of resources allocation. The aim of the present study was to assess the impact, on the budget of the Italian National Healthcare Service, of generic antiretroviral drugs and of new antiretroviral drugs entering the market from 2015 to 2019. METHODS: A budget impact model was developed in order to forecast the rate of use of ARTs, based on trends observed within the Lombardy Region (Italy), on clinical experts' opinion, and the consequent impact on the Italian NHS budget in a five year time horizon. Different scenarios were developed, considering the sole introduction of generic drugs, of new drugs, and their cumulative effects. A multivariate sensitivity analysis was also performed. RESULTS: The cumulative use of generic drugs and new drugs would lead to annual savings of 4.6 million ? ( 0.6 %) in 2015; 16.9 million ? (-2.1 %) in 2016; 19.4 million ? (-2.4 %) in 2017; 51.1 million ? (-6.1 %) in 2018 and -110.3 million ? (-12.8 %) in 2019. The impact of new drugs in percentage terms is +2.0 % in 2015, +3.4 % in 2016, +3.9 % in 2017, +5.7 % in 2018 and +7.7 % in 2019. The impact of generic drugs would lead to savings of 4.9 million ? in 2015, 18.6 million ? in 2016, 22.8 million ? in 2017, 76.5 million ? in 2018 and 187.4 million ? in 2019. The sensitivity analysis showed annual mean savings for the Italian NHS ranging from 12.6 million ?, -1.5 % compared to the base case scenario (decreasing all the rates of transition used in the simulation, and increasing the cost of generic drugs) to 76.0 million ?, -9.1 % (increasing all the rates of transition used in the simulation, and decreasing the cost of generic and new drugs). CONCLUSIONS: The use of antiretroviral generic drugs may lead to savings that would compensate the expenditure increase due to new, innovative drugs available on the market. PMID- 26259844 TI - A Review of Supportive Interventions Targeting Individuals or Couples Undergoing Infertility Treatment: Directions for the Development of Interventions. AB - The purpose of this systematic review is to explore the types, content, and outcomes of different psychosocial approaches used in existing interventions for infertile individuals or couples. Relevant intervention studies published in English between 2000 and 2014 were searched using the electronic databases MEDLINE, PsycINFO, and CINHAL Plus. A total of 23 articles were identified and included in this review. Cognitive behavioral therapy (CBT), acceptance and commitment therapy (ACT), and counseling were the most commonly adopted psychosocial interventions for infertile individuals or couples. After reviewing the various approaches, directions are given on the development of interventions for couples suffering from infertility. PMID- 26259843 TI - Promoting Educational Resiliency in Youth with Incarcerated Parents: The Impact of Parental Incarceration, School Characteristics, and Connectedness on School Outcomes. AB - The United States has the highest incarceration rate in the world, and as a result, one of the largest populations of incarcerated parents. Growing evidence suggests that the incarceration of a parent may be associated with a number of risk factors in adolescence, including school drop out. Taking a developmental ecological approach, this study used multilevel modeling to examine the association of parental incarceration on truancy, academic achievement, and lifetime educational attainment using the National Longitudinal Survey of Adolescent Health (48.3 % female; 46 % minority status). Individual characteristics, such as school and family connectedness, and school characteristics, such as school size and mental health services, were examined to determine whether they significantly reduced the risk associated with parental incarceration. Our results revealed small but significant risks associated with parental incarceration for all outcomes, above and beyond individual and school level characteristics. Family and school connectedness were identified as potential compensatory factors, regardless of parental incarceration history, for academic achievement and truancy. School connectedness did not reduce the risk associated with parental incarceration when examining highest level of education. This study describes the school related risks associated with parental incarceration, while revealing potential areas for school-based prevention and intervention for adolescents. PMID- 26259845 TI - Pathway analysis for RNA-Seq data using a score-based approach. AB - A variety of pathway/gene-set approaches have been proposed to provide evidence of higher-level biological phenomena in the association of expression with experimental condition or clinical outcome. Among these approaches, it has been repeatedly shown that resampling methods are far preferable to approaches that implicitly assume independence of genes. However, few approaches have been optimized for the specific characteristics of RNA-Seq transcription data, in which mapped tags produce discrete counts with varying library sizes, and with potential outliers or skewness patterns that violate parametric assumptions. We describe transformations to RNA-Seq data to improve power for linear associations with outcome and flexibly handle normalization factors. Using these transformations or alternate transformations, we apply recently developed null approximations to quadratic form statistics for both self-contained and competitive pathway testing. The approach provides a convenient integrated platform for RNA-Seq pathway testing. We demonstrate that the approach provides appropriate type I error control without actual permutation and is powerful under many settings in comparison to competing approaches. Pathway analysis of data from a study of F344 vs. HIV1Tg rats, and of sex differences in lymphoblastoid cell lines from humans, strongly supports the biological interpretability of the findings. PMID- 26259846 TI - Selecting polymers for two-phase partitioning bioreactors (TPPBs): Consideration of thermodynamic affinity, crystallinity, and glass transition temperature. AB - Two-phase partitioning bioreactor technology involves the use of a secondary immiscible phase to lower the concentration of cytotoxic solutes in the fermentation broth to subinhibitory levels. Although polymeric absorbents have attracted recent interest due to their low cost and biocompatibility, material selection requires the consideration of properties beyond those of small molecule absorbents (i.e., immiscible organic solvents). These include a polymer's (1) thermodynamic affinity for the target compound, (2) degree of crystallinity (wc ), and (3) glass transition temperature (Tg ). We have examined the capability of three thermodynamic models to predict the partition coefficient (PC) for n butyric acid, a fermentation product, in 15 polymers. Whereas PC predictions for amorphous materials had an average absolute deviation (AAD) of >=16%, predictions for semicrystalline polymers were less accurate (AAD >= 30%). Prediction errors were associated with uncertainties in determining the degree of crystallinity within a polymer and the effect of absorbed water on n-butyric acid partitioning. Further complications were found to arise for semicrystalline polymers, wherein strongly interacting solutes increased the polymer's absorptive capacity by actually dissolving the crystalline fraction. Finally, we determined that diffusion limitations may occur for polymers operating near their Tg , and that the Tg can be reduced by plasticization by water and/or solute. This study has demonstrated the impact of basic material properties that affects the performance of polymers as sequestering phases in TPPBs, and reflects the additional complexity of polymers that must be taken into account in material selection. PMID- 26259847 TI - Action induction by visual perception of rotational motion. AB - A basic process in the planning of everyday actions involves the integration of visually perceived movement characteristics. Such processes of information integration often occur automatically. The aim of the present study was to examine whether the visual perception of spatial characteristics of a rotational motion (rotation direction) can induce a spatially compatible action. Four reaction time experiments were conducted to analyze the effect of perceiving task irrelevant rotational motions of simple geometric figures as well as of gymnasts on a horizontal bar while responding to color changes in these objects. The results show that the participants react faster when the directional information of a rotational motion is compatible with the spatial characteristics of an intended action. The degree of complexity of the perceived event does not play a role in this effect. The spatial features of the used biological motion were salient enough to elicit a motion based Simon effect. However, in the cognitive processing of the visual stimulus, the critical criterion is not the direction of rotation, but rather the relative direction of motion (direction of motion above or below the center of rotation). Nevertheless, this conclusion is tainted with reservations since it is only fully supported by the response behavior of female participants. PMID- 26259848 TI - Pharmacological and psychosomatic treatments for an elderly patient with severe nausea and vomiting in reaction to postoperative stress. AB - Here we present a case of successful treatment employing a mixed approach including pharmacological and psychosomatic treatments for a 72-year-old woman who experienced severe nausea and vomiting in reaction to postoperative stress from gastric cancer surgery. This case demonstrates that appropriate provision of psychosomatic treatments, including a psychotherapeutic session and autogenic training, enhances the efficacy of pharmacotherapy. PMID- 26259849 TI - Patient Preferences for Injectable Treatments for Multiple Sclerosis in the United States: A Discrete-Choice Experiment. AB - BACKGROUND AND OBJECTIVE: Patients' perceptions and experiences of medication efficacy, medication adverse events, dosing frequency, and dosing complexity have been found to influence adherence to injectable disease-modifying treatments (DMTs) in patients with multiple sclerosis (MS). The aim of this study was to quantify patient preferences for features of injectable DMTs for MS. METHODS: Adult patients in the United States (US) with a self-reported diagnosis of MS completed an online discrete-choice experiment survey to assess preference for a number of features of a hypothetical injectable DMT. Patients chose hypothetical treatments in paired comparisons, where each treatment was described by features or attributes, including the number of years until disability progression, the number of relapses in the next 4 years, injection time, the frequency of injections, the occurrence of flu-like symptoms (FLS), and severity of injection site reactions. Random-parameters logit regression parameters were used to calculate preference weights of attribute levels and the relative importance of changes in treatment features. RESULTS: Of the 205 patients who completed the survey, 192 provided sufficient data for analysis. The results indicated a broad range of tradeoffs that patients would be willing to make. With regard to this, the relative importance of an improvement in the number of years until disability progression from 1 to 2 (i.e., vertical distance between preference weights for these attribute levels) was 0.9 [95% confidence interval (CI) 0.5-1.2], the relative importance of this change was approximately equivalent to that of an improvement from 12 injections per month to two (mean 0.8, 95% CI 0.4-1.2), or approximately equivalent to a decrease from four to one relapses in the next 4 years (mean 0.8, 95% CI 0.5-1.2), or FLS 3 days after every injection to 3 days after some injections (mean 1.0, 95% CI 0.6-1.4). CONCLUSIONS: These results suggest that an improvement in treatment efficacy may be as important as a reduction in injection frequency or a reduction in some adverse events for patients who self-administer injectable DMTs for MS. Understanding the preferences of patients who use injectable treatments will inform the development of such treatments, which may in turn improve patient medication adherence and well-being. PMID- 26259850 TI - Behavioural characteristics of the Prader-Willi syndrome related biallelic Snord116 mouse model. AB - Prader-Willi syndrome (PWS) is the predominant genetic cause of obesity in humans and is associated with several behavioural phenotypes such as altered motoric function, reduced activity, and learning disabilities. It can include mood instability and, in some cases, psychotic episodes. Recently, the Snord116 gene has been associated with the development of PWS, however, it's contribution to the behavioural aspects of the disease are unknown. Here we show that male and female mice lacking Snord116 on both alleles exhibit normal motor behaviours and exploration but do display task-dependent alterations to locomotion and anxiety related behaviours. Sociability is well developed in Snord116 deficient mice as are social recognition memory, spatial working memory, and fear-associated behaviours. No sex-specific effects were found. In conclusion, the biallelic Snord116 deficiency mouse model exhibits particular endophenotypes with some relevance to PWS, suggesting partial face validity for the syndrome. PMID- 26259851 TI - Role of cerebellar adrenomedullin in blood pressure regulation. AB - Adrenomedullin (AM) and their receptor components, calcitonin-receptor-like receptor (CRLR) and receptor activity-modifying protein (RAMP1, RMP2 and RAMP3) are widely expressed in the central nervous system, including cerebellum. We have shown that AM binding sites are altered in cerebellum during hypertension, suggesting a role for cerebellar adrenomedullinergic system in blood pressure regulation. To further evaluate the role of AM in cerebellum, we assessed the expression of AM, RAMP1, RAMP2, RAMP3 and CRLR in the cerebellar vermis of 8 and 16week old spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. In addition, the effect of microinjection of AM into rat cerebellar vermis on arterial blood pressure (BP) was determined. Animals were sacrificed by decapitation and cerebellar vermis was dissected for quantification of AM, CRLR, RAMP1, RAMP2 and RAMP3 expression using western blot analysis. Another group of male, 16week old SHR and WKY rats was anesthetized, and a cannula was implanted in the cerebellar vermis. Following recovery AM (0.02 to 200pmol/5MUL) or vehicle was injected into cerebellar vermis. BP was determined, before and after treatments, by non-invasive plethysmography. In addition, to establish the receptor subtype involved in AM action in vivo, animals received microinjections of AM22-52 (200pmol/5MUL), an AM1 receptor antagonist, or the CGRP1 receptor antagonist, CGRP8-37 (200pmol/5MUL) into the cerebellar vermis, administered simultaneously with AM or vehicle microinjection. Cannulation was verified post mortem with the in situ injection of a dye solution. Our findings demonstrated that the expression of CRLR, RAMP1 and RAMP3 was higher in cerebellum of SHR rats, while AM and RAMP2 expression was lower than those of WKY rats, both in 8 and 16week old rats. In vivo microinjection of AM into the cerebellar vermis caused a profound, dose dependent, hypotensive effect in SHR but not in normotensive WKY rats. Coinjections of a putative AM receptor antagonist, AM22-52 abolished the decreases in mean arterial pressure (MAP) evoked by AM, showing that AM acts through its AM1 receptor in the vermis to reduce MAP. These findings demonstrate a dysregulation of cerebellar AM-system during hypertension, and suggest that cerebellar AM plays an important role in the regulation of BP. Likewise; they constitute a novel mechanism of BP control which has not been described so far. PMID- 26259852 TI - Effects of amlodipine on ischaemia/reperfusion injury in the rat testis. AB - The aim of this study was to examine the effects of amlodipine (AML) in rat testicular torsion/detorsion damage. In this study, rats were divided into eight groups: (i) sham; (ii) testicular ischaemia, 2 h of ischaemia; (iii) testicular ischaemia/reperfusion (I/R), 2 h of ischaemia followed by 2 h of reperfusion; (iv) ischaemia + AML (5 mg kg(-1)) administered 30 min before ischaemia; (v) ischaemia + AML (10 mg kg(-1)) administered 30 min before ischaemia; (vi) and (vii) I/R + AML (5 mg kg(-1)) and I/R + AML (10 mg kg(-1)) administered 1.5 h after the induction of ischaemia, respectively, and at the end of a 2-h ischaemia period and a 2-h reperfusion period applied; and (viii) sham + AML (10 mg kg( 1)). Significant decreases in levels of superoxide dismutase and glutathione were observed in ischaemia and reperfusion groups when compared with healthy controls. These antioxidant levels increased in AML groups while malondialdehyde levels significantly decreased. While increases in tumour necrosis factor-alpha and transforming growth factor-beta levels were found in the torsion and detorsion groups, significant decreases in the levels of these inflammatory cytokines were observed in the treatment groups. These results demonstrate that AML significantly produced protective effects on testis tissue damage that occurs in the torsion/detorsion model via biochemical, histopathological and molecular pathways. PMID- 26259853 TI - A mechanical model to investigate the role of the nucleus during confined cell migration. PMID- 26259854 TI - Intraoperative MR Imaging in Neurosurgery. AB - Intraoperative magnetic resonance imaging (iMRI) has dramatically expanded and nowadays presents state-of-the-art technique for image-guided neurosurgery, facilitating critical precision and effective surgical treatment of various brain pathologies. Imaging hardware providing basic imaging sequences as well as advanced MRI can be seamlessly integrated into routine surgical environments, which continuously leads to emerging indications for iMRI-assisted surgery. Besides the obvious intraoperative diagnostic yield, the initial clinical benefits have to be confirmed by future-controlled long-term studies. PMID- 26259855 TI - The availability and accessibility of nutrition information in fast food outlets in five states post-menu labelling legislation in New South Wales. AB - OBJECTIVES: 1) Explore the availability and accessibility of fast food energy and nutrient information post-NSW menu labelling legislation in states with and without menu labelling legislation. 2) Determine whether availability and accessibility differed compared with pre-menu labelling legislation in NSW. METHODS: We visited 210 outlets of the five largest fast food chains in five Australian states to observe the availability and accessibility of energy and nutrient information. Results were compared with 197 outlets surveyed pre-menu labelling. RESULTS: Most outlets (95%) provided energy values, half provided nutrient values and 3% provided information for all menu items. The total amount of information available increased post-NSW menu labelling implementation (473 versus 178 pre-implementation, p<0.001); however, fewer outlets provided nutrient values (26% versus 97% pre-implementation, p<0.001). CONCLUSIONS: Fast food chains surveyed had voluntarily introduced menu labelling nationally. However, more nutrient information was available in-store in 2010, showing that fast food chains are able to provide comprehensive nutrition information, yet they have stopped doing so. IMPLICATIONS: Menu labelling legislation should compel fast food chains to provide accessible nutrition information including nutrient values in addition to energy for all menu items in-store. Additionally, public education campaigns are needed to ensure customers can use menu labelling. PMID- 26259856 TI - Cerebellar meningeal melanocytoma associated with nevus of Ota: An extremely rare case. PMID- 26259857 TI - Low-frequency stimulation of STN-DBS reduces aspiration and freezing of gait in patients with PD. PMID- 26259858 TI - Optimal achieved blood pressure in acute intracerebral hemorrhage: INTERACT2. PMID- 26259859 TI - Teaching NeuroImages: NMDA encephalomyelitis with MRI abnormalities isolated to ventral spinal cord gray matter. PMID- 26259861 TI - Acquirement of DNA copy number variations in non-small cell lung cancer metastasis to the brain. AB - Brain metastasis is a major complication of non-small cell lung cancer (NSCLC) and leads to most of the mortality of this disease. However, the biological mechanisms and molecular features in brain metastasis of NSCLC are poorly understood. In the present study, we compared whole-genome copy number variations (CNVs) between a primary lung adenocarcinoma and secondary metastatic brain lesion from the same patient using array comparative genomic hybridization (aCGH). The number of CNV regions was markedly higher in the secondary metastatic tumor than the primary tumor in the lung. In detail, the common CNVs in both tumors included gains of 7p22, 7p12-p11, 7q11, 7q22, 21q22, and 19q13; gains of 1p33-p34, 1q22, 5p13 and 14q11 whereas losses of 3p, 4q31, 5q, 11p15, Xp21-p22 and Xq21 were identified only in the secondary lesion. Gene Ontology enrichment analysis revealed that the genes with amplified copy numbers in both tumors were related to such processes as DNA replication and mismatch repair. Genes only amplified in the metastatic tumor were enriched in processes that include leukocyte migration and organ development, and genes with a lower copy number in the secondary tumor included the processes of proteolysis regulation, negative regulation of cell proliferation and cell adhesion. These findings provided new insight into the genomic mechanism of the spread of lung adenocarcinoma to the brain, and the candidate genes identified serve as novel indicators or putative targets in NSCLC brain metastasis. PMID- 26259862 TI - US psychologists banned from participating in national security interrogations. PMID- 26259863 TI - Calcified central venous catheter fibrin sheath: case report and review of the literature. AB - We present a 6-year-old girl with acute lymphoblastic leukemia who demonstrated on chest X-ray a radiopacity in the superior vena cava after removal of an implanted venous access device. This radiopacity was initially thought to be a retained catheter fragment. On review of previous imaging, we were able to document the temporal development of a calcified catheter cast as distinct from the catheter. This case represents a rare consequence of central venous catheterization in children. Knowledge of this finding as a possible complication may help avoid performance of unnecessary follow-up imaging or invasive procedures. PMID- 26259864 TI - The use of 18F-FDG PET ratios in the differential diagnosis of common malignant brain tumors. AB - OBJECTIVE: This study examined the use of positron emission tomography (PET) ratios to improve the diagnostic ability of 18F-FDG PET/computed tomography (CT) in the differentiation of enhancing brain metastases, central nervous system lymphomas, and gliomas. MATERIALS AND METHODS: Seventy-six patients with malignant brain tumors and available magnetic resonance imaging and PET/CT examinations were included. RESULTS: Among standardized uptake value (SUV) related parameters tested, tumor maximum SUV to ipsilateral cortex maximum SUV ratio (Tmax:WMimax) and maximum SUV (SUVmax) proved to be the two most valuable parameters for differential diagnosis. CONCLUSION: In addition to SUVmax, Tmax:WMimax also seems to provide helpful information for the differential diagnosis of lymphomas from other malignant brain tumors. PMID- 26259865 TI - Correlation of clot distribution with morphometric measurements and pleuroparenchymal findings in acute pulmonary embolism: experience with 692 cases. AB - PURPOSE: The aim of the study is to determine if clot distribution in acute pulmonary embolism (PE) correlates with morphometric measurements of right heart function, reflux in inferior vena cava (IVC), and pleuroparenchymal findings. MATERIALS AND METHODS: A total of 692 computed tomography pulmonary angiographies with PE were enrolled, and patients were grouped according to clot localization. Parenchymal findings, morphometric measurements of right heart function, and contrast reflux in IVC were noted. RESULTS: Differences were found between groups for most measurements, and central PE was associated with significantly higher right ventricle (RV) and pulmonary artery diameters, ratio of RV diameter to left ventricle (LV) diameter (RV/LV) >= 1, and IVC reflux. CONCLUSIONS: Significant association was present among clot distribution in PE, morphometrics, IVC reflux, and pleuroparenchymal findings. PMID- 26259866 TI - Screening mammography-detected ductal carcinoma in situ: mammographic features based on breast cancer subtypes. AB - We evaluated the mammographic and histopathologic features of screening mammography-detected ductal carcinoma in situ (DCIS) based on the breast cancer subtypes determined by immunohistochemistry. A total of 94 patients with 94 screening mammography-detected DCIS were included in this study. Mammographically, human epidermal growth factor receptor 2 (HER2)-positive DCIS was more commonly associated with calcifications than estrogen receptor (ER) positive and triple-negative DCIS (P=.003). Histopathologically, HER2-positive DCIS and triple-negative DCIS were associated with high nuclear grade (P <= .001) and comedo necrosis (P <= .001) than ER-positive DCIS. PMID- 26259867 TI - Swedish osteoporosis care. AB - The objective of this study was to review and describe the current state of Swedish osteoporosis care and to highlight ongoing challenges. This report encompasses quantitative health outcomes based on Swedish registry data as well as organizational and management aspects. Swedish osteoporosis care is characterized by a significant burden of disease, difficulties in identifying high-risk patients, and fragmented pathways for patients in need of secondary fracture prevention. This report aimed to describe the current state, gaps, and challenges in Swedish osteoporosis care, using Swedish national databases, questionnaires, and interviews with healthcare representatives. A secondary aim was to develop quality and process measures to compare differences between counties and to use those measures to describe the interaction between quantitative health outcomes and aspects of care organization and management. In conjunction with fractures, a considerably smaller proportion of men are treated than women, and a smaller proportion of older women are treated compared to younger groups. Between 3 and 16 % of patients receive treatment after a fracture, and the treatment rate in this patient group can likely increase. In addition to an unsatisfactory treatment rate, a limited number of those treated continue treatment throughout the recommended treatment durations, leading to increased risk of fracture. With a substantial variation between counties, there is a clear difficulty to identify non-persistent patients and switch to an alternative treatment. Collaboration around the patient across specialties has been lacking, and systems for secondary prevention have been concentrated to a few counties. However, when this study was conducted, there was a general trend towards implementing regional care programs. This report suggests possible strategies for improving quality of care and, hopefully, it can provide a basis for future evaluations and regional improvement of osteoporosis care in Sweden and other countries. PMID- 26259868 TI - Community water fluoridation: attitudes and opinions from the New Zealand Oral Health Survey. AB - OBJECTIVE: To report the responses of adult participants in the 2009 New Zealand Oral Health Survey (NZOHS) to questions about community water fluoridation (CWF). METHODS: The study used quantitative data from the NZOHS. All adult participants aged 18 years and over in the nationally representative NZOHS sample were included in the study (n=3475). Univariate analysis and multinominal logistic regression models were used to examine the associations between variables. RESULTS: Overall, 57.7% of respondents thought that there were dental benefits to adding fluoride to drinking water and 31.7% responded that they did not know. More than 45% of respondents did not know whether there were health risks from adding fluoride to drinking water. Overall, 42.0% of respondents were strongly or somewhat in favour of CWF. CONCLUSION AND IMPLICATIONS: People in the Maori, Pacific and Asian ethnic groups, from the two most deprived quintiles, with no education after high school and who brushed their teeth less than twice a day expressed significantly greater uncertainty about CWF than other population groups. This study suggests further research is required to gain a greater understanding of health literacy about CWF and the cultural appropriateness of CWF in NZ. PMID- 26259869 TI - Parathyroid Hormone-Related Protein Analogs as Osteoporosis Therapies. AB - The only bone anabolic agent currently available for osteoporosis treatment is parathyroid hormone (PTH)-either its N-terminal 1-34 fragment or the whole molecule of 1-84 aminoacids-whose intermittent administration stimulates new bone formation by targeting osteoblastogenesis and osteoblast survival. PTH-related protein (PTHrP) is an abundant factor in bone which shows N-terminal homology with PTH and thus exhibits high affinity for the same PTH type 1 receptor in osteoblasts. Therefore, it is not surprising that intermittently administered N terminal PTHrP peptides induce bone anabolism in animals and humans. Furthermore, the C-terminal region of PTHrP also elicits osteogenic features in vitro in osteoblastic cells and in various animal models of osteoporosis. In this review, we discuss the current concepts about the cellular and molecular mechanisms whereby PTHrP may induce anabolic actions in bone. Pre-clinical studies and clinical data using N-terminal PTHrP analogs are also summarized, pointing to PTHrP as a promising alternative to current bone anabolic therapies. PMID- 26259871 TI - How to get the best deal. AB - Floral scents and nectar attract both pollinators and other animals that may reduce the plant's fitness, and therefore put flowering plants in a challenging situation. PMID- 26259870 TI - Physiological roles of bacillithiol in intracellular metal processing. AB - Glutathione (GSH) is an abundantly produced low-molecular-weight (LMW) thiol in many organisms. However, a number of Gram-positive bacteria do not produce GSH, but instead produce bacillithiol (BSH) as one of the major LMW thiols. Similar to GSH, studies have found that BSH has various roles in the cell, including protection against hydrogen peroxide, hypochlorite and disulfide stress. BSH also participates in the detoxification of thiol-reactive antibiotics and the electrophilic metabolite methylglyoxal. Recently, a number of studies have highlighted additional roles for BSH in the processing of intracellular metals. Herein, we examine the potential functions of BSH in the biogenesis of Fe-S clusters, cytosolic metal buffering and the prevention of metal intoxication. PMID- 26259872 TI - ISG15 counteracts Listeria monocytogenes infection. AB - ISG15 is an interferon-stimulated, linear di-ubiquitin-like protein, with anti viral activity. The role of ISG15 during bacterial infection remains elusive. We show that ISG15 expression in nonphagocytic cells is dramatically induced upon Listeria infection. Surprisingly this induction can be type I interferon independent and depends on the cytosolic surveillance pathway, which senses bacterial DNA and signals through STING, TBK1, IRF3 and IRF7. Most importantly, we observed that ISG15 expression restricts Listeria infection in vitro and in vivo. We made use of stable isotope labeling in tissue culture (SILAC) to identify ISGylated proteins that could be responsible for the protective effect. Strikingly, infection or overexpression of ISG15 leads to ISGylation of ER and Golgi proteins, which correlates with increased secretion of cytokines known to counteract infection. Together, our data reveal a previously uncharacterized ISG15-dependent restriction of Listeria infection, reinforcing the view that ISG15 is a key component of the innate immune response. PMID- 26259873 TI - Ultrastructural analysis of adult mouse neocortex comparing aldehyde perfusion with cryo fixation. AB - Analysis of brain ultrastructure using electron microscopy typically relies on chemical fixation. However, this is known to cause significant tissue distortion including a reduction in the extracellular space. Cryo fixation is thought to give a truer representation of biological structures, and here we use rapid, high pressure freezing on adult mouse neocortex to quantify the extent to which these two fixation methods differ in terms of their preservation of the different cellular compartments, and the arrangement of membranes at the synapse and around blood vessels. As well as preserving a physiological extracellular space, cryo fixation reveals larger numbers of docked synaptic vesicles, a smaller glial volume, and a less intimate glial coverage of synapses and blood vessels compared to chemical fixation. The ultrastructure of mouse neocortex therefore differs significantly comparing cryo and chemical fixation conditions. PMID- 26259874 TI - Integrating between-host transmission and within-host immunity to analyze the impact of varicella vaccination on zoster. AB - Varicella-zoster virus (VZV) causes chickenpox and reactivation of latent VZV causes herpes zoster (HZ). VZV reactivation is subject to the opposing mechanisms of declining and boosted VZV-specific cellular mediated immunity (CMI). A reduction in exogenous re-exposure 'opportunities' through universal chickenpox vaccination could therefore lead to an increase in HZ incidence. We present the first individual-based model that integrates within-host data on VZV-CMI and between-host transmission data to simulate HZ incidence. This model allows estimating currently unknown pivotal biomedical parameters, including the duration of exogenous boosting at 2 years, with a peak threefold to fourfold increase of VZV-CMI; the VZV weekly reactivation probability at 5% and VZV subclinical reactivation having no effect on VZV-CMI. A 100% effective chickenpox vaccine given to 1 year olds would cause a 1.75 times peak increase in HZ 31 years after implementation. This increase is predicted to occur mainly in younger age groups than is currently assumed. PMID- 26259875 TI - Association between high-resolution computed tomography findings and the IASLC/ATS/ERS classification of small lung adenocarcinomas in Japanese patients. AB - OBJECTIVES: The detection rate of small pulmonary nodules has recently increased and new techniques have been developed to improve diagnostic yield. The IASLC/ATS/ERS classification demonstrated a difference in prognosis depending on the histological subtypes of lung adenocarcinoma. We evaluated the association between high-resolution computed tomography (HRCT) findings and the classification of these tumors. METHODS: We reviewed the data of 220 lung adenocarcinoma (<=3 cm) patients who received complete resection with lymph node dissection in our hospital. From the HRCT findings, the tumors were classified into the following 3 categories: pure-solid nodules, part-solid nodules, or pure ground-glass opacity (GGO) nodules. Pathological invasion factor (PIF) was evaluated by the degree of blood vessel invasion, lymphatic permeation, and visceral pleural invasion. RESULTS: The tumors were classified as pure GGO nodules in 16 patients, part-solid nodules in 91, and pure-solid nodules in 113 from the HRCT findings. Tumors were diagnosed as noninvasive or minimally invasive adenocarcinomas (NMIADs) in 44 patients, and invasive adenocarcinomas (IADs) in 176. Lymph node metastasis was present in 31 patients (14.1%) and PIF in 101 (45.9%). All pure-solid nodules were IADs with a high PIF frequency (75.2%) or with lymph node metastasis (26.5%). All pure GGO nodules were NMIADs or lepidic-predominant adenocarcinomas. Among the part-solid nodules, IAD was detected in 67.0% of the patients and PIF in 16.5%. The consolidation/tumor (C/T) ratio and consolidation size were associated with IAD (optimal cut-off values: 0.4 and 8mm, respectively) and PIF (0.8 and 15 mm, respectively). CONCLUSIONS: The HRCT findings correlated with the IASLC/ATS/ERS classification and were useful for evaluating the histological nature of the tumors. Most pure-solid tumors had the potential for high-grade malignancy, including PIF and lymph node metastasis. For part-solid tumors, the C/T ratio and consolidation size were important for predicting PIF and for diagnosing IAD according to this classification. PMID- 26259876 TI - Cost-effectiveness analysis of EGFR mutation testing and gefitinib as first-line therapy for non-small cell lung cancer. AB - OBJECTIVES: The combination use of gefitinib and epidermal growth factor receptor (EGFR) testing is a standard first-line therapy for patients with non-small cell lung cancer (NSCLC). Here, we examined the cost-effectiveness of this approach in Japan. MATERIALS AND METHODS: Our analysis compared the 'EGFR testing strategy', in which EGFR mutation testing was performed before treatment and patients with EGFR mutations received gefitinib while those without mutations received standard chemotherapy, to the 'no-testing strategy,' in which genetic testing was not conducted and all patients were treated with standard chemotherapy. A three-state Markov model was constructed to predict expected costs and outcomes for each strategy. We included only direct medical costs from the healthcare payer's perspective. Outcomes in the model were based on those reported in the Iressa Pan Asia Study (IPASS). The incremental cost-effectiveness ratio (ICER) was calculated using quality-adjusted life-years (QALYs) gained. Sensitivity and scenario analyses were conducted. RESULTS: The incremental cost and effectiveness per patient of the 'EGFR testing strategy' compared to the 'no-testing strategy' was estimated to be approximately JPY122,000 (US$1180; US$1=JPY104 as of February 2014) and 0.036 QALYs. The ICER was then calculated to be around JPY3.38 million (US$32,500) per QALY gained. These results suggest that the 'EGFR testing strategy' is cost-effective compared with the 'no-testing strategy' when JPY5.0 million to 6.0 million per QALY gained is considered an acceptable threshold. These results were supported by the sensitivity and scenario analyses. CONCLUSION: The combination use of gefitinib and EGFR testing can be considered a cost-effective first-line therapy compared to chemotherapy such as carboplatin paclitaxel for the treatment for NSCLC in Japan. PMID- 26259877 TI - Prognostic significance of the lymphocyte-to-monocyte ratio in patients with malignant pleural mesothelioma. AB - OBJECTIVES: Chronic inflammation plays a key role in the pathogenesis of malignant pleural mesothelioma (MPM) as a result of asbestos exposure. Several inflammation-based prognostic scores including the lymphocyte-to-monocyte ratio (LMR), Glasgow Prognostic Score (GPS), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) reportedly predict survival in many malignancies, while the role of LMR in MPM remains unclear. The aim of this study was to evaluate the clinical value of LMR and to compare the prognostic value of these inflammation-based scores in predicting overall survival (OS) in MPM. MATERIALS AND METHODS: One hundred and fifty patients with histologically proven MPM were included in this retrospective study. Kaplan-Meier curves and multivariate Cox-regression analyses were calculated for OS. The area under the receiver operating characteristics curve (AUC) was calculated to compare the discriminatory ability of each scoring system. RESULTS: An elevated LMR was significantly associated with prolonged OS. Patients with LMR <2.74 had significantly poor survival compared with LMR >=2.74 (median, 5.0 versus 14.0 months; p=0.000). The LMR consistently had a higher AUC value at 6 months (0.722), 12 months (0.712), and 24 months (0.670), compared with other scores. Multivariate analysis showed that the LMR was independently associated with OS. CONCLUSIONS: The LMR is an independent prognostic marker for OS in patients with MPM and is superior to other inflammation-based prognostic scores with respect to prognostic ability. PMID- 26259878 TI - Characterization of hypoxia in malignant pleural mesothelioma with FMISO PET-CT. AB - OBJECTIVES: Malignant pleural mesothelioma (MPM) is a chemotherapy resistant tumor with a poor prognosis. Hypoxia is increasingly recognized as an important factor in tumor aggressiveness and cellular resistance to chemotherapy and radiation treatment. This prospective pilot study was performed with [F-18] fluoromisonidazole (FMISO) PET-CT to characterize hypoxia in patients with MPM. MATERIALS AND METHODS: Twenty prospectively recruited patients with histologically or cytologically confirmed MPM not currently receiving systemic or local treatment underwent both FMISO and fluorodeoxyglucose (FDG) PET-CT scans within 2 weeks. FMISO and FDG PET-CT scans were independently analyzed visually and semi-quantitatively using SUVmax and tumor to background ratio (TBR) in order to assess tumor hypoxia and metabolic activity. Lesion by lesion analysis was performed in sites of measurable pleural masses. RESULTS: Visual analysis demonstrated tumor FMISO activity in 17 of 20 patients, and tumor FDG activity in 19 of 20 patients. Focal areas of bulky tumor were most likely to demonstrate hypoxia. In 19 patients suitable for semi-quantitative analysis the median FDG SUVmax was 6.4 (range 1.9-19.1), median FMISO SUVmax was 2.5 (range 1.4-3.7) and median FMISO TBR was 1.8 (1.1-2.5). There was a positive correlation between intensity of metabolic activity and hypoxia (r=0.72, p=0.001). Lesion by lesion analysis demonstrated a positive correlation between tumor thickness and FMISO activity (r=0.77, p<0.001). CONCLUSION: This pilot study confirms that MPM is a tumor with significant areas of hypoxia, particularly in dominant tumor masses. The relationship of tumor hypoxia to effectiveness of chemotherapy and/or radiation therapy warrants prospective assessment. PMID- 26259879 TI - Decision framework for platform decommissioning in California. AB - This article describes the overall decision framework for eventual decisions about decommissioning the 27 operating oil and gas platforms offshore southern California. These platforms will eventually reach the end of their useful lifetimes (estimated between 2015 and 2030, although specific dates have not been determined). Current law and regulations allow for alternative uses in lieu of the complete removal required in existing leases. To prepare for eventual decommissioning, the California Natural Resources Agency initiated an in-depth process to identify and investigate issues surrounding possible decommissioning alternatives. The detailed evaluation of alternatives focused on 2-complete removal and artificial reefing that included partial removal to 85 feet below the waterline. These were selected after a comparison of the technical and economic feasibility of several potential alternatives, availability of a legal framework for implementation, degree of interest from proponents, and relative acceptance by state and federal decision makers. Despite California's history of offshore oil and gas production, only 7 decommissioning projects have been completed and these were all relatively small and close to shore. In contrast, nearly 30% of the California platforms are in water depths (as much as 1200 feet) that exceed any decommissioning project anywhere in the world. Most earlier projects considered an artificial reefing alternative but none were implemented and all platforms were completely removed. Future decisions about decommissioning must grapple with a more complex decision context involving greater technological and logistical challenges and cost, a wider range of viable options, tradeoffs among environmental impacts and benefits, and an intricate maze of laws, regulations, and authorities. The specific engineering differences between complete and partial removal provide an explicit basis for a thorough evaluation of their respective impacts. PMID- 26259880 TI - The LcrG Tip Chaperone Protein of the Yersinia pestis Type III Secretion System Is Partially Folded. AB - The type III secretion system (T3SS) is essential in the pathogenesis of Yersinia pestis, the causative agent of plague. A small protein, LcrG, functions as a chaperone to the tip protein LcrV, and the LcrG-LcrV interaction is important in regulating protein secretion through the T3SS. The atomic structure of the LcrG family is currently unknown. However, because of its predicted helical propensity, many have suggested that the LcrG family forms a coiled-coil structure. Here, we show by NMR and CD spectroscopy that LcrG lacks a tertiary structure and it consists of three partially folded alpha-helices spanning residues 7-38, 41-46, and 58-73. NMR titrations of LcrG with LcrV show that the entire length of a truncated LcrG (residues 7-73) is involved in binding to LcrV. However, there is regional variation in how LcrG binds to LcrV. The C-terminal region of a truncated LcrG (residues 52-73) shows tight binding interaction with LcrV while the N-terminal region (residues 7-51) shows weaker interaction with LcrV. This suggests that there are at least two binding events when LcrG binds to LcrV. Biological assays and mutagenesis indicate that the C-terminal region of LcrG (residues 52-73) is important in blocking protein secretion through the T3SS. Our results reveal structural and mechanistic insights into the atomic conformation of LcrG and how it binds to LcrV. PMID- 26259881 TI - S-Nitrosylation of Calcium-Handling Proteins in Cardiac Adrenergic Signaling and Hypertrophy. AB - RATIONALE: The regulation of calcium (Ca(2+)) homeostasis by beta-adrenergic receptor (betaAR) activation provides the essential underpinnings of sympathetic regulation of myocardial function, as well as a basis for understanding molecular events that result in hypertrophic signaling and heart failure. Sympathetic stimulation of the betaAR not only induces protein phosphorylation but also activates nitric oxide-dependent signaling, which modulates cardiac contractility. Nonetheless, the role of nitric oxide in betaAR-dependent regulation of Ca(2+) handling has not yet been explicated fully. OBJECTIVE: To elucidate the role of protein S-nitrosylation, a major transducer of nitric oxide bioactivity, on betaAR-dependent alterations in cardiomyocyte Ca(2+) handling and hypertrophy. METHODS AND RESULTS: Using transgenic mice to titrate the levels of protein S-nitrosylation, we uncovered major roles for protein S-nitrosylation, in general, and for phospholamban and cardiac troponin C S-nitrosylation, in particular, in betaAR-dependent regulation of Ca(2+) homeostasis. Notably, S nitrosylation of phospholamban consequent upon betaAR stimulation is necessary for the inhibitory pentamerization of phospholamban, which activates sarcoplasmic reticulum Ca(2+)-ATPase and increases cytosolic Ca(2+) transients. Coincident S nitrosylation of cardiac troponin C decreases myocardial sensitivity to Ca(2+). During chronic adrenergic stimulation, global reductions in cellular S nitrosylation mitigate hypertrophic signaling resulting from Ca(2+) overload. CONCLUSIONS: S-Nitrosylation operates in concert with phosphorylation to regulate many cardiac Ca(2+)-handling proteins, including phospholamban and cardiac troponin C, thereby playing an essential and previously unrecognized role in cardiac Ca(2+) homeostasis. Manipulation of the S-nitrosylation level may prove therapeutic in heart failure. PMID- 26259882 TI - Specific Physician Orders Improve Pain Detection and Pain Reports in Nursing Home Residents: Preliminary Data. AB - Despite evidence that many nursing home residents' pain is poorly managed, reasons for this poor management remain unanswered. The aim of this study was to determine if specific order sets related to pain assessment would improve pain management in nursing home (NH) residents. Outcomes included observed nurse pain assessment queries and resident reports of pain. The pretest/post-test study was performed in a 240-bed for-profit nursing home in the mid-southern region of the United States and participants were 43 nursing home residents capable of self consent. Medical chart abstraction was performed during a 2-week (14-day) period before the implementation of specific order sets for pain assessment (intervention) and a 2-week (14-day) period after the intervention. Trained research assistants observed medication administration passes and performed participant interviews after each medication pass. One month after intervention implementation, 1 additional day of observations was conducted to determine data reliability. Nurses were observed to ask residents about pain more frequently, and nurses continued to ask about pain at higher rates 1 month after the intervention was discontinued. The proportion of residents who reported pain also significantly increased in response to increased nurse queries (e.g., "Do you have any pain right now?"), which underscores the importance of nurses directly asking residents about pain. Notably 70% of this long-stay NH population only told the nurses about their pain symptoms when asked directly. Findings uncover that using specific pain order sets seems to improve the detection of pain, which should be a routine part of nursing assessment. PMID- 26259883 TI - Pelvic Floor and Urinary Distress in Women with Fibromyalgia. AB - Fibromyalgia (FM) patients were recently found to have more symptom burden from bothersome pelvic pain syndromes that women seeking care for pelvic floor disease at a urogynecology clinic. We sought to further characterize pelvic floor symptoms in a larger sample of FM patients using of validated questionnaires. Female listserv members of the Fibromyalgia Information Foundation completed an online survey of three validated questionnaires: the Pelvic Floor Distress Inventory 20 (PFDI-20), the Pelvic Pain, Urgency and Frequency Questionnaire (PUF), and the Revised Fibromyalgia Impact Questionnaire (FIQR). Scores were characterized using descriptive statistics. Patients (n = 204 with complete data on 177) were on average 52.3 +/- 11.4 years with a mean parity of 2.5 +/- 1.9. FM severity based on FIQR score (57.2 +/- 14.9) positively correlated with PFDI-20 total 159.08 +/- 55.2 (r = .34, p < .001) and PUF total 16.54 +/- 7 (r = .36, p < .001). Women with FM report significantly bothersome pelvic floor and urinary symptoms. Fibromyalgia management should include evaluation and treatment of pelvic floor disorders recognizing that pelvic distress and urinary symptoms are associated with more severe FM symptoms. Validated questionnaires, like the ones used in this study, are easily incorporated into clinical practice. PMID- 26259884 TI - Recurrent, alternating orbital inflammation. PMID- 26259885 TI - Neuroactive steroids and stress axis regulation: Pregnancy and beyond. AB - The hypothalamo-pituitary-adrenal (HPA) axis plays a critical role in regulating responses to stress and long term dysregulation of the HPA axis is associated with higher rates of mood disorders. There are circumstances where the HPA axis is more or less responsive to stress. For example, during late pregnancy ACTH and corticosterone responses to stress are markedly suppressed, whereas in offspring born to mothers that experienced repeated stress during pregnancy, the HPA axis is hyper-responsive to stress. Neuroactive steroids such as allopregnanolone, tetrahydrodeoxycorticosterone (THDOC) and androstanediol can modulate HPA axis activity and concentrations of some neuroactive steroids in the brain are altered during pregnancy and following stress. Thus, here altered neurosteroidogenesis is proposed as a mechanism that could underpin the dynamic changes in HPA axis regulation typically observed in late pregnant and in prenatally stressed individuals. In support of this hypothesis, evidence in rats demonstrates that elevated levels of allopregnanolone in pregnancy induce a central inhibitory opioid mechanism that serves to minimize stress-induced HPA axis activity. Conversely, in prenatally stressed rodents, where HPA axis stress responses are enhanced, evidence indicates the capacity of the brain for neurosteroidogenesis is reduced. Understanding the mechanisms involved in adaptations in HPA axis regulation may provide insights for manipulating stress sensitivity and for developing therapies for stress-related disorders in humans. PMID- 26259886 TI - A rare case of Klippel-Feil syndrome associated with atlantoaxial rotatory subluxation, atlanto-occipital fusion, and spina bifida. PMID- 26259887 TI - Beyond Cervical Length: A Pilot Study of Ultrasonic Attenuation for Early Detection of Preterm Birth Risk. AB - The purpose of this study was to determine whether cervical ultrasonic attenuation could identify women at risk of spontaneous preterm birth. During pregnancy, women (n = 67) underwent from one to five transvaginal ultrasonic examinations to estimate cervical ultrasonic attenuation and cervical length. Ultrasonic data were obtained with a Zonare ultrasound system with a 5- to 9-MHz endovaginal transducer and processed offline. Cervical ultrasonic attenuation was lower at 17-21 wk of gestation in the SPTB group (1.02 dB/cm-MHz) than in the full-term birth groups (1.34 dB/cm-MHz) (p = 0.04). Cervical length was shorter (3.16 cm) at 22-26 wk in the SPTB group than in the women delivering full term (3.68 cm) (p = 0.004); cervical attenuation was not significantly different at this time point. These findings suggest that low attenuation may be an additional early cervical marker to identify women at risk for SPTB. PMID- 26259888 TI - Preliminary Results on the Feasibility of Using ARFI/SWEI to Assess Cutaneous Sclerotic Diseases. AB - In this study, acoustic radiation force impulse (ARFI) and shear wave elasticity imaging (SWEI) were applied to the skin to investigate the feasibility of their use in assessing sclerotic skin diseases. Our motivation was to develop a non invasive imaging technology with real-time feedback of sclerotic skin disease diagnosis. This paper shows representative results from an ongoing study, recruiting patients with and without sclerosis. The stiffness of the imaged site was evaluated using two metrics: mean ARFI displacement magnitude and bulk shear wave speed inside the region of interest (ROI). In a subject with localized graft versus host disease (GVHD), the mean ARFI displacement inside sclerotic skin was 61% lower (p < 0.01) and shear wave speed 128% higher (p < 0.005) compared to those in normal skin-indicating stiffer mechanical properties in the sclerotic skin. This trend persisted through disease types. We conclude ARFI and SWEI can successfully differentiate sclerotic lesions from normal dermis. PMID- 26259889 TI - Pre-operative Ultrasonographic Evaluation of Axillary Lymph Nodes in Breast Cancer Patients: For Which Group Still of Additional Value and in Which Group Cause for Special Attention? AB - A non-invasive and widely available method for pre-operative evaluation of the axilla is axillary ultrasonography (US). The purpose of this study was to evaluate the diagnostic accuracy of axillary US and fine-needle aspiration cytology in a large cohort of breast cancer patients. The sensitivity and specificity of US and fine-needle aspiration cytology in our cohort of 1124 patients were 42.2% and 97.1%, respectively. As the number of axillary nodes increased, sensitivity increased. The percentage of false-negative US results was 18.9%; patients in this subgroup were significantly younger, had larger tumors, more often had lymph vascular invasion and were more likely to have estrogen receptor-positive tumors. Ultrasonography in combination with fine-needle aspiration cytology is useful in the pre-operative workup of breast cancer patients, especially patients with three or more nodal metastases. Special attention should be paid to younger women with larger tumors in whom a larger percentage of false-negative results are obtained. PMID- 26259890 TI - The serotonin receptor mediates changes in autonomic neurotransmission and gastrointestinal transit induced by heat-killed Lactobacillus brevis SBC8803. AB - Lactobacilli exhibit several health benefits in mammals, including humans. Our previous reports established that heat-killed Lactobacillus brevis SBC8803 (SBC8803) increased both efferent gastric vagal nerve activity and afferent intestinal vagal nerve activity in rats. We speculated that this strain could be useful for the treatment of gastrointestinal (GI) disorders. In this study, we examined the effects of SBC8803 on peristalsis and the activity of the efferent celiac vagal nerve innervating the intestine in rats. First, we examined the effects of intraduodenal (ID) administration of SBC8803 on efferent celiac vagal nerve activity (efferent CVNA) in urethane-anesthetised rats using electrophysiological studies. The effects of intravenous injection of the serotonin 5-HT3 receptor antagonist granisetron on changes in efferent CVNA due to ID administration of SBC8803 were also investigated. Finally, the effects of oral gavage of SBC8803 on GI transit were analysed using the charcoal propulsion method in conscious rats treated with or without granisetron. ID administration of SBC8803 increased efferent CVNA. Pretreatment with granisetron eliminated SBC8803-dependent changes in efferent CVNA. Furthermore, oral gavage of SBC8803 significantly accelerated GI transit, while pretreatment with granisetron inhibited GI transit. Our findings suggested that SBC8803 increased efferent CVNA and GI transit of charcoal meal via 5-HT3 receptors. Moreover, SBC8803 enhanced the activity of efferent vagal nerve innervating the intestine and promoted peristalsis via 5-HT3 receptors. PMID- 26259891 TI - Mixed culture models for predicting intestinal microbial interactions between Escherichia coli and Lactobacillus in the presence of probiotic Bacillus subtilis. AB - Bacillus has been proposed as a probiotic due to its in vivo effectiveness in the gastrointestinal tract through antimicrobial activities. The present study investigates the effects of Lactobacillus alone or in the presence of Bacillus subtilis MA139 on the inhibition of pathogenic Escherichia coli K88. Mixed cultures were used to predict the possible interactions among these bacteria within the intestinal tract of animals. B. subtilis MA139 was first assayed for its inhibition against E. coli K88 both under shaking and static culture conditions. A co-culture assay was employed under static conditions to test the inhibitory effects of Lactobacillus reuteri on E. coli K88, with or without addition of B. subtilis MA139. The results showed that B. subtilis MA139 had marked inhibition against E. coli K88 under shaking conditions and weak inhibition under static conditions. Lactobacillus alone as well as in combination with B. subtilis MA139 spores exerted strong inhibition against E. coli K88 under static conditions. However, the inhibition by Lactobacillus in combination with B. subilis spores was much higher than that by Lactobacillus alone (P<0.01). B. subtilis MA139 significantly decreased the pH and oxidation-reduction potential values of the co-culture broth compared to that of Lactobacillus alone (P<0.05). The viability of Lactobacillus increased when co-cultured with B. subtilis MA139 because of significantly higher Lactobacillus counts and lower pH values in the broth (P<0.05). The role of Bacillus in the mixed culture models suggests that Bacillus may produce beneficial effects by increasing the viability of lactobacilli and subsequently inhibiting the growth of pathogenic E. coli. Therefore, the combination of Bacillus and Lactobacillus species as a probiotic is recommended. PMID- 26259892 TI - Effects of synbiotic on anthropometry, lipid profile and oxidative stress in obese children. AB - Recent studies have suggested some beneficial effects of probiotics and/or prebiotics on obesity in adults; such experience is limited in children and adolescents. This study was an open-label, randomised, controlled study including children with primary obesity. The first group was treated with a standard method with a reduced calorie intake and increased physical activity. The second group received add-on daily synbiotic supplementation during one month. The aim of this study was to evaluate potential effects of a synbiotic on anthropometric measurements, lipid profile and oxidative stress parameters. One month of supplementation of the synbiotic resulted in a significant reduction of weight (P<0.001) and body mass index (P<0.01). Changes (% reduction comparing to baseline) in anthropometric measurements, were significantly higher in the children receiving the additional synbiotic supplement (P<0.05). The percentage of children with weight loss was higher in the synbiotic group, but not statistically significant (71.4 vs 64.2%, P>0.05). At the 30(th) day of synbiotic intervention, serum total cholesterol, low density lipoprotein cholesterol and total oxidative stress levels significantly declined (P<0.05). Changes in serum lipid levels were significantly higher in the synbiotic group (P<0.05). Changes in serum total oxidative stress levels before and after the intervention period, were significant in synbiotic group (P<0.01). In our study, changes in weight, body mass index, and triceps skinfold thickness were higher in the group receiving the one month synbiotic supplement thin in the standard method group. The supplement tested also had a beneficial effect on lipid profile and total oxidative stress. To the best of our knowledge, this is the first study showing the effects of synbiotics on oxidative stress in obese patients with an additional effect on weight loss regarding to previous studies. PMID- 26259893 TI - Prevalence of depression and its associated factors in patients with type 2 diabetes: A cross-sectional study in Dhaka, Bangladesh. AB - Depression is a common feature in patients with type 2 diabetes and often remains undetected and untreated, causing increased morbidity and mortality. We explored the prevalence of co-morbid depression and its associated factors, including major life-events among patients with type 2 diabetes in Bangladesh. We conducted a cross-sectional study among 515 patients with type 2 diabetes between September 2013 and July 2014 in a tertiary hospital in Dhaka city. We assessed depression using Patient Health Questionnaire-9 (PHQ-9) with predefined cut-off scores of 5, 10, 15 and 20 to indicate minimal, mild, moderate, moderately-severe, and severe depression. Associations between depression and its associated factors were explored using univariate and multivariate regression. Overall, 61.9% participants had depressive symptoms, and the prevalence was higher among females (70.9%) compared to males (50.6%). One-third (35.7%) of participants had mild depression and 36.2% had moderate to severe depression. In the multivariate analysis, factors significantly associated with depression were: age<=60 years (OR: 2.1, 95% CI=1.2-3.6; p<=0.006), female gender (OR=1.9, 95% CI=1.3-3.0; p<=0.002), those having 1-3 complications (OR=2.3, 95% CI=1.2-4.3; p=0.010), experienced loss of business or crop failure (OR=2.1, 95% CI=1.2-3.6; p=0.006), major family conflicts (OR=2.2, 95% CI=1.4-3.5; p<=0.001), separation or deaths of family members or divorce (OR=2.2, 95% CI=1.4-3.5; p<=0.001), and those who experienced unavailability of food or medicines (OR=2.2, 95% CI=1.0-4.5; p=0.038). Patients with diabetes, especially females, those having other complications, and major life-events should routinely be screened for symptoms of depression with adequate management of these conditions. PMID- 26259894 TI - Comorbidity, knowledge and attitude towards sex among patients with Dhat syndrome: A retrospective study. AB - This study aimed to assess the knowledge about sex, attitude towards sex, prevalence of psychiatric comorbidity and relationship of the comorbidity with onset of symptoms of Dhat syndrome. Treatment records of 264 patients diagnosed with Dhat syndrome were reviewed for clinical profile including psychiatric comorbidity and sexual dysfunction and information on sexual knowledge and attitude using Sex Knowledge and Attitude Questionnaire (SKAQ-II). None of the patients gave all the correct responses on the SKAQ-II. Poor knowledge about sexual matters was not limited to the semen formation only, but also involved other aspects of sexuality, like masturbation, relationship of pregnancy with orgasm in women, breast feeding and pregnancy, relationship of sexual desire with addictive drugs and sexually transmitted diseases can be cured by having sex with a virgin girl. Higher level of education showed significant association with better sexual knowledge and liberal attitude. There was significant positive correlation between sexual knowledge and attitude. About half (51.9%) of patients had at least one comorbid psychiatric disorder and/or sexual dysfunction. Among the psychiatric disorders, depressive disorders were the most common and premature ejaculation was the most common comorbid sexual dysfunction. Among those with comorbidity, symptoms of Dhat syndrome preceded the onset of other disorders. Patients with Dhat syndrome have high rates of comorbidity and poor sexual knowledge and less liberal attitude, which was not only limited to loss of semen but also involves other spheres of sexuality. Accordingly psychoeducation in patients of Dhat syndrome should not be limited to addressing the myths and lack of knowledge about semen formation, but also should address poor sexual knowledge on all the aspects related to sexuality and the negative attitude towards sex. PMID- 26259895 TI - Contraception use and impact on pregnancy prevention in women participating in an HIV prevention trial in South Africa. AB - BACKGROUND: Unplanned pregnancy rates in South Africa are high. Effective use of contraception is therefore an essential public health intervention to prevent unplanned pregnancies. This study describes contraception use and its impact on pregnancy in women participating in HIV prevention research and its implications for public health practice. METHOD: A secondary analysis of sociodemographic, behavioural, contraception use, and pregnancy incidence data was conducted amongst women participating in the Microbicides Development Programme (MDP) 301 trial conducted in Durban, South Africa. Log-rank tests were carried out to compare the pregnancy incidence between women who reported use of injectable contraceptive methods compared to women using oral contraceptive pills, using condoms and other methods (intrauterine device, traditional methods and natural methods). The effect of types of contraceptives on pregnancy incidence was assessed using Cox proportional hazards regression models. RESULTS: Of the 2018 women enrolled, injectable contraception was the most commonly used method (52%) compared to pills, condoms for pregnancy prevention and other methods. Injectable contraception use was associated with lower crude pregnancy incidence of 4.4 per 100 woman-years [95% confidence interval (95% CI 3.3-5.9)] compared to women using pills [19.3 per 100 woman-years (95% CI 13.3-28.0)], condoms [19.7 per 100 woman-years (95% CI 16.3-23.6)] and other methods [11.5 per 100 woman-years (95% CI 7.5-17.6)]. This effect remained significant when adjusted for age, level of education, condom use at last sex act [hazard ratio 0.27, (95% CI 0.16-0.47, p<0.001)]. CONCLUSION: Injectable contraception offered a high level of protection against pregnancies among women in Durban. TRIAL REGISTRATION NUMBER: ISRCTN64716212. PMID- 26259896 TI - Assessing feasibility and acceptability of a brief intervention for risky alcohol consumption in sexual health clinic attendees: a randomised controlled trial. AB - OBJECTIVES: To assess the feasibility and acceptability of screening attendees at a sexual health clinic (SHC) for alcohol misuse, and delivering a brief intervention (BI). To explore the effect of this BI on drinking and sexual behaviour. METHODS: A consecutive sample of consenting SHC attendees aged >=16 years were screened using Alcohol Use Disorders Identification Test Consumption (AUDIT-C). Men scoring >=5 and women scoring >=4 were invited to complete the full AUDIT, alcohol diary and baseline questionnaire. INTERVENTIONS: Participants were randomised to receive BI by a trained sexual health professional or a standard alcohol leaflet (usual care, UC). All were followed up for changes in alcohol and sexual behaviour at 6 weeks and 6 months. A fidelity check and staff focus group were undertaken. RESULTS: Of 664 participants screened, 215 (32%) were eligible for randomisation and 207 were included in the final analysis: 103 (BI) and 104 (UC). Follow-up rates were 54% and 47% at 6 weeks and 6 months, respectively. Both groups reduced alcohol consumption though the degree of change did not differ between them. There was some evidence of positive changes in sexual health risk in both groups. BI was delivered as intended, adding 5 minutes to the consultation, and staff feedback was positive. CONCLUSIONS: Alcohol misuse was common in SHC attendees. Systematic assessment and BI for alcohol misuse was feasible and acceptable to staff and patients. Identification and provision of standard information alone appeared to influence drinking and sexual behaviour. TRIAL REGISTRATION NUMBER: ISRCTN19452424. PMID- 26259898 TI - Band Propagation, Scaling Laws, and Phase Transition in a Precipitate System. 2. Computational Study. AB - In this second paper, we introduce a chemical kinetic model that investigates the dynamics of the experimental Ni(2+)/NH3-OH(-) Liesegang system characterized by a pattern of beta-nickel hydroxide bands led by a growing pulse of alpha-nickel hydroxide. The model is based on a system of reaction-diffusion equations describing the precipitation reaction and dissolution of the nickel hydroxide polymorphs by ammonia. The hydroxide ions are assumed to be static whereas ammonia serves as a diffusing "vehicle" that supplies the hydroxide ions along the precipitation zone, and these ions in turn react with the static Ni(2+) ions. The precipitation-diffusion equations are coupled to nucleation, polymorphic transition, and growth rate equations, each of which is characterized by a critical constant specific to the solid phase dynamics. In the proposed model, priority is given to polymorphic transition rather than nucleation. This implies that the critical constants must be subject to a constraint different than that derived for the Lifshitz-Slyozov instability encountered in classical Liesegang patterns. Numerical simulations confirm the validity of our model and the derived constraint. The pulse position and width are found to scale in time as t(alpha) with alpha ? 0.5, in agreement with the experimental results. Finally, the mass of the bands is shown to oscillate in time, suggesting competition between growth and polymorphic transition on one side and dissolution on the other. PMID- 26259899 TI - dUTPase: the frequently overlooked enzyme encoded by many retroviruses. AB - Retroviruses are among the best studied viruses in last decades due to their pivotal involvement in cellular processes and, most importantly, in causing human diseases, most notably-acquired immunodeficiency syndrome (AIDS) that is triggered by human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2, respectively). Numerous studied were conducted to understand the involvement of the three cardinal retroviral enzymes, reverse transcriptase, integrase and protease, in the life cycle of the viruses. These studies have led to the development of many inhibitors of these enzymes as anti-retroviral specific drugs that are used for routine treatments of HIV/AIDS patients. Interestingly, a fourth virus-encoded enzyme, the deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) is also found in several major retroviral groups. The presence and the importance of this enzyme to the life cycle of retroviruses were usually overlooked by most retrovirologists, although the occurrence of dUTPases, particularly in beta-retroviruses and in non-primate retroviruses, is known for more than 20 years. Only more recently, retroviral dUTPases were brought into the limelight and were shown in several cases to be essential for viral replication. Therefore, it is likely that future studies on this enzyme will advance our knowledge to a level that will allow designing novel, specific and potent anti dUTPase drugs that are effective in combating retroviral diseases. The aim of this review is to give concise background information on dUTPases in general and to summarize the most relevant data on retroviral dUTPases and their involvement in the replication processes and pathogenicity of the viruses, as well as in possibly-associated human diseases. PMID- 26259900 TI - Functional role of lysine 12 in Leishmania major AQP1. AB - Leishmania major aquaglyceroporin (AQP1) is an adventitious metalloid channel that allows the bidirectional movement of arsenite and antimonite. Here we demonstrate that AQP1 is subjected to proteasome-dependent degradation. Treatment of Leishmania promastigotes with the proteasome inhibitor MG132 resulted in increased AQP1 accumulation. Site-directed mutagenesis in AQP1 revealed that alteration of lysine 12 to either alanine or arginine improves protein stability. AQP1 expression is stabilized by mitogen-activated protein kinase 2 (MPK2). Cells expressing a dominant-negative MPK2 mutant exhibited severely reduced AQP1 expression, which could be reversed upon addition of MG132. Interestingly, the dominant-negative MPK2 mutant could not destabilize either AQP1K12A or AQP1K12R. While stabilization of AQP1 by MPK2 leads to its relocalization from flagellum to the entire surface of the parasite, altered AQP1K12A or AQP1K12R was restricted to flagellum only. Our data demonstrate that lysine 12 is targeted for proteasomal degradation of AQP1 and plays an integral role in subcellular localization of AQP1 as well as its interaction with MPK2. This work also raises the possibility that a strategy combining antimonial with a proteasome inhibitor may be an effective combination regimen against diverse forms of leishmaniasis. PMID- 26259901 TI - Motor cortex excitability is not differentially modulated following skill and strength training. AB - AIM: A single session of skill or strength training can modulate the primary motor cortex (M1), which manifests as increased corticospinal excitability (CSE) and decreased short-latency intra-cortical inhibition (SICI). We tested the hypothesis that both skill and strength training can propagate the neural mechanisms mediating cross-transfer and modulate the ipsilateral M1 (iM1). METHODS: Transcranial magnetic stimulation (TMS) measured baseline CSE and SICI in the contralateral motor cortex (cM1) and iM1. Participants completed 4 sets of unilateral training with their dominant arm, either visuomotor tracking, metronome-paced strength training (MPST), self-paced strength training (SPST) or control. Immediately post training, TMS was repeated in both M1s. RESULTS: Motor evoked potentials (MEPs) increased and inhibition was reduced for skill and MPST training from baseline in both M1s. Self-paced strength training and control did not produce changes in CSE and SICI when compared to baseline in both M1s. After training, skill and MPST increased CSE and decreased SICI in cM1 compared to SPST and control. Skill and MPST training decreased SICI in iM1 compared to SPST and control post intervention; however, CSE in iM1 was not different across groups post training. CONCLUSION: Both skill training and MPST facilitated an increase in CSE and released SICI in iM1 and cM1 compared to baseline. Our results suggest that synchronizing to an auditory or a visual cue promotes neural adaptations within the iM1, which is thought to mediate cross transfer. PMID- 26259902 TI - Hyperthermia aggravates status epilepticus-induced epileptogenesis and neuronal loss in immature rats. AB - This study tightly controlled seizure duration and severity during status epilepticus (SE) in postnatal day 10 (P10) rats, in order to isolate hyperthermia as the main variable and to study its consequences. Body temperature was maintained at 39 +/- 1 degrees C in hyperthermic SE rats (HT+SE) or at 35 +/- 1 degrees C in normothermic SE animals (NT+SE) during 30 min of SE, which was induced by lithium-pilocarpine (3 mEq/kg, 60 mg/kg) and terminated by diazepam and cooling to NT. All video/EEG measures of SE severity were similar between HT+SE and NT+SE pups. At 24h, neuronal injury was present in the amygdala in the HT+SE group only, and was far more severe in the hippocampus in HT+SE than NT+SE pups. Separate groups of animals were monitored four months later for spontaneous recurrent seizures (SRS). Only HT+SE animals developed convulsive SRS. Both HT+SE and NT+SE animals developed electrographic SRS (83% vs. 55%), but SRS frequency and severity were higher in hyperthermic animals (12.5 +/- 3.5 vs. 4.2 +/- 2.0 SRS/day). The density of hilar neurons was lower, thickness of the amygdala and perirhinal cortex was reduced, and lateral ventricles were enlarged in HT+SE over NT+SE littermates and HT/NT controls. In this model, hyperthermia greatly increased the epileptogenicity of SE and its neuropathological sequelae. PMID- 26259903 TI - Orexin-A potentiates L-type calcium/barium currents in rat retinal ganglion cells. AB - Two neuropeptides, orexin-A and orexin-B (also called hypocretin-1 and -2), have been implicated in sleep/wake regulation, feeding behaviors via the activation of two subtypes of G-protein-coupled receptors: orexin 1 and orexin 2 receptors (OX1R and OX2R). While the expression of orexins and orexin receptors is immunohistochemically revealed in retinal neurons, the function of these peptides in the retina is largely unknown. Using whole-cell patch-clamp recordings in rat retinal slices, we demonstrated that orexin-A increased L-type-like barium currents (IBa,L) in ganglion cells (GCs), and the effect was blocked by the selective OX1R antagonist SB334867, but not by the OX2R antagonist TCS OX2 29. The orexin-A effect was abolished by intracellular dialysis of GDP-beta-S/GPAnt 2A, a Gq protein inhibitor, suggesting the mediation of Gq. Additionally, during internal dialysis of the phosphatidylinositol (PI)-phospholipase C (PLC) inhibitor U73122, orexin-A did not change the IBa,L of GCs, whereas the orexin-A effect persisted in the presence of the phosphatidylcholine (PC)-PLC inhibitor D609. The orexin-A-induced potentiation was not seen with internal infusion of Ca(2+)-free solution or when inositol 1,4,5-trisphosphate (IP3)-sensitive Ca(2+) release from intracellular stores was blocked by heparin/xestospongins-C. Moreover, the orexin-A effect was mimicked by the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate, but was eliminated when PKC was inhibited by bisindolylmaleimide IV (Bis-IV)/Go6976. Neither adenosine 3',5' cyclic monophosphate (cAMP)-protein kinase A (PKA) nor guanosine 3',5'-cyclic monophosphate (cGMP)-protein kinase G (PKG) signaling pathway was likely involved, as orexin-A persisted to potentiate the IBa,L of GCs no matter these two pathways were activated or inhibited. These results suggest that, by activating OX1R, orexin-A potentiates the IBa,L of rat GCs through a distinct Gq/PI-PLC/IP3/Ca(2+)/PKC signaling pathway. PMID- 26259904 TI - Placenta accreta: we can do better! PMID- 26259905 TI - Three-year continuation of reversible contraception. AB - OBJECTIVE: The objective of this analysis was to estimate the 3-year continuation rates of long-acting reversible contraceptive (LARC) methods and to compare these rates to non-LARC methods. STUDY DESIGN: The Contraceptive CHOICE Project (CHOICE) was a prospective cohort study that followed 9256 participants with telephone surveys at 3 and 6 months, then every 6 months for 2-3 years. We estimated 3-year continuation rates of baseline methods that were chosen at enrollment. The LARC methods include the 52-mg levonorgestrel intrauterine device; the copper intrauterine device, and the subdermal implant). These were then compared to rates to non-LARC hormonal methods (depot medroxyprogesterone acetate, oral contraceptive pills, contraceptive patch, and vaginal ring). Eligibility criteria for this analysis included participants who started their baseline chosen method by the 3-month survey. Participants who discontinued their method to attempt conception were censored. We used a Cox proportional hazard model to adjust for confounding and to estimate the hazard ratio for risk of discontinuation. RESULTS: Our analytic sample consisted of 4708 CHOICE participants who met inclusion criteria. Three-year continuation rates were 69.8% for users of the levonorgestrel intrauterine device, 69.7% for copper intrauterine device users, and 56.2% for implant users. At 3 years, continuation was 67.2% among LARC users and 31.0% among non-LARC users (P < .001). After adjustment for age, race, education, socioeconomic status, parity, and history of sexually transmitted infection, the hazard ratio for risk of discontinuation was 3-fold higher among non-LARC method users than LARC users (adjusted hazard ratio, 3.08; 95% confidence interval, 2.80-3.39). CONCLUSION: Three-year continuation of the 2 intrauterine devices approached 70%. Continuation of LARC methods was significantly higher than non-LARC methods. PMID- 26259906 TI - Characterization of the host inflammatory response following implantation of prolapse mesh in rhesus macaque. AB - OBJECTIVE: We sought to determine the predominant cell type (macrophage, T lymphocyte, B lymphocyte, mast cell) within the area of implantation of the prototypical polypropylene mesh, Gynemesh PS (Ethicon, Somerville, NJ); and to determine the phenotypic profile (M1 proinflammatory, M2 antiinflammatory) of the macrophage response to 3 different polypropylene meshes: Gynemesh PS (Ethicon), and 2 lower-weight, higher-porosity meshes, UltraPro (Ethicon) and Restorelle (Coloplast, Humblebaek, Denmark). STUDY DESIGN: Sacrocolpopexy was performed following hysterectomy in rhesus macaques. Sham-operated animals served as controls. At 12 weeks postsurgery, the vagina-mesh complex was excised and the host inflammatory response was evaluated. Hematoxylin and eosin was used to perform routine histomorphologic evaluation. Identification of leukocyte (CD45(+)) subsets was performed by immunolabeling for CD68 (macrophage), CD3 (T lymphocyte), CD20 (B lymphocyte), and CD117 (mast cell). M1 and M2 macrophage subsets were identified using immunolabeling (CD86(+) and CD206(+), respectively), and further evaluation was performed using enzyme-linked immunosorbent assay for 2 M1 (tumor necrosis factor-alpha and interleukin [IL] 12) and 2 M2 (IL-4 and IL-10) cytokines. RESULTS: Histomorphologic evaluation showed a dense cellular response surrounding each mesh fiber. CD45(+) leukocytes accounted for 21.4 +/- 5.4% of total cells within the perimesh area captured in a *20 field, with macrophages as the predominant leukocyte subset (10.5 +/- 3.9% of total cells) followed by T lymphocytes (7.3 +/- 1.7%), B lymphocytes (3.0 +/- 1.2%), and mast cells (0.2 +/- 0.2%). The response was observed to be more diffuse with increasing distance from the fiber surface. Few leukocytes of any type were observed in sham-operated animals. Immunolabeling revealed polarization of the macrophage response toward the M1 phenotype in all mesh groups. However, the ratio of M2:M1 macrophages was increased in the fiber area in UltraPro (P = .033) and Restorelle (P = .016) compared to Gynemesh PS. In addition, a shift toward increased expression of the antiinflammatory cytokine IL-10 was observed in Restorelle as compared to Gynemesh PS (P = .011). CONCLUSION: The host response to mesh consists predominantly of activated, proinflammatory M1 macrophages at 12 weeks postsurgery. However, this response is attenuated with implantation of lighter-weight, higher-porosity mesh. While additional work is required to establish causal relationships, these results suggest a link among the host inflammatory response, mesh textile properties, and clinical outcomes in the repair of pelvic organ prolapse. PMID- 26259907 TI - Reply: To PMID 25499262. PMID- 26259908 TI - Minimal stimulation IVF vs conventional IVF: a randomized controlled trial. AB - BACKGROUND: Minimal stimulation in vitro fertilization (mini-in vitro fertilization) is an alternative in vitro fertilization treatment protocol that may reduce ovarian hyperstimulation syndrome, multiple pregnancy rates, and cost while retaining high live birth rates. OBJECTIVE: We performed a randomized noninferiority controlled trial with a prespecified border of 10% that compared 1 cycle of mini-in vitro fertilization with single embryo transfer with 1 cycle of conventional in vitro fertilization with double embryo transfer. STUDY DESIGN: Five hundred sixty-four infertile women (<39 years old) who were undergoing their first in vitro fertilization cycle were allocated randomly to either mini-in vitro fertilization or conventional in vitro fertilization. The primary outcome was cumulative live birth rate per woman over a 6-month period. Secondary outcomes included ovarian hyperstimulation syndrome, multiple pregnancy rates, and gonadotropin use. The primary outcome was cumulative live birth per randomized woman within a time horizon of 6 months. RESULTS: Five hundred sixty four couples were assigned randomly between February 2009 and August 2013 with 285 couples allocated to mini-in vitro fertilization and 279 couples allocated to conventional in vitro fertilization. The cumulative live birth rate was 49% (140/285) for mini-in vitro fertilization and 63% (176/279) for conventional in vitro fertilization (relative risk, 0.76; 95% confidence interval, 0.64-0.89). There were no cases of ovarian hyperstimulation syndrome after mini-in vitro fertilization compared with 16 moderate/severe ovarian hyperstimulation syndrome cases (5.7%) after conventional in vitro fertilization. The multiple pregnancy rates were 6.4% in mini-in vitro fertilization compared with 32% in conventional in vitro fertilization (relative risk, 0.25; 95% confidence interval, 0.14-0.46). Gonadotropin consumption was significantly lower with mini-in vitro fertilization compared with conventional in vitro fertilization (459 +/- 131 vs 2079 +/- 389 IU; P < .0001). CONCLUSION: Compared with conventional in vitro fertilization with double embryo transfer, mini-in vitro fertilization with single embryo transfer lowers live birth rates, completely eliminates ovarian hyperstimulation syndrome, reduces multiple pregnancy rates, and reduces gonadotropin consumption. PMID- 26259909 TI - Dichorionic twin ultrasound surveillance: sonography every 4 weeks significantly underperforms sonography every 2 weeks: results of the Prospective Multicenter ESPRiT Study. AB - OBJECTIVE: A 2-week ultrasound scanning schedule for monochorionic twins is endorsed widely. There is a lack of robust data to inform a schedule for the surveillance of dichorionic gestations. We aimed to determine how ultrasound scanning that is performed at 2- or 4-week intervals (or every 4 weeks before 32 weeks' gestation and every 2 weeks thereafter) may impact the prenatal detection of fetal growth restriction (FGR) and ultimately influence timing of delivery. STUDY DESIGN: In a consecutive cohort of 789 dichorionic twin pregnancies that were recruited prospectively for the multicenter Evaluation of Sonographic Predictors of Restricted Growth in Twins study, ultrasound determination of fetal growth and interrogation of umbilical and middle cerebral artery Doppler scans were performed every 2 weeks from 24 weeks' gestation until delivery. Complete delivery and perinatal outcome data were recorded for all pregnancies. Where delivery was prompted by FGR, abnormal umbilical artery Doppler examination or poor biophysical profile and in the absence of ruptured membranes, onset of labor, preeclampsia, or antepartum hemorrhage, the delivery was considered "ultrasound-indicated." For ultrasound-indicated deliveries, detection probabilities for FGR/abnormal umbilical artery Doppler scans/poor biophysical were determined according to the interval between examinations, by the suppression if alternate examination data. RESULTS: Among 789 dichorionic twin pregnancies, 66 pairs (8%) had an "ultrasound indicated" delivery. Detection of FGR was reduced from 88-69%, and detection of abnormal umbilical artery Doppler was reduced from 82-62% when a 4-week ultrasound schedule was simulated. Both of these reductions reached statistical significance. There was a nonsignificant trend toward a reduction in the recording of oligohydramnios with a 4-week interval between examinations. CONCLUSION: This study suggests that the ultrasound surveillance program of every 2 weeks that is recommended currently for monochorionic twins should be extended to dichorionic gestations. PMID- 26259910 TI - Laparoscopic sacrocolpopexy: demonstration of a nerve-sparing technique. PMID- 26259911 TI - Increased Activation Amplitude Levels of Gluteus Medius in Women During Isometric and Dynamic Conditions Following a 4-week Protocol of Low-load Eccentric Exercises. AB - BACKGROUND: The dysfunction of gluteus medius (GMed) has been implicated in other musculoskeletal disorders including low back pain and lower limb injuries. The purpose of this study was to use a protocol involving low-load eccentric exercises to observe the effects on the three subdivisions of GMed activation through surface electromyography (sEMG) and digital dynamometry. METHODS: Eleven female subjects having femoral instability participated in a 4-week protocol (three sessions per week/non-consecutive days). At each session, two low-load eccentric exercises (12% of maximal isometric voluntary contraction [MVIC]) in abduction, extension and external rotation were applied to the hip joint. The sEMG of the GMed subdivisions (anterior, mid and posterior) during a squat and MVIC were assessed. The digital dynamometry was also assessed during MVIC. Parametric paired t-test was used to compare the results before and after treatment with alpha = 0.05. RESULTS: The results showed an increased sEMG activity of GMed (middle and posterior portions) during isometric voluntary contraction and squat after the protocol. No difference was noted to the anterior subdivision of GMed. Another finding was the significant difference to the dynamometry results, showing improvements to generate strength to the GMed as a whole muscle in abduction. CONCLUSION: The 4-week exercise protocol was effective to increase the activation of the GMed middle and posterior subdivisions, improving also the capacity to generate strength as a whole muscle during the proposed tasks. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26259912 TI - Eculizumab in Transplant-Associated Thrombotic Microangiopathy. AB - INTRODUCTION: Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare entity with no standard of care and high mortality, despite the use of plasma exchange. METHODS: Using specific search terms, all cases having TA-TMA treated with eculizumab and indexed in MEDLINE (English language only) by November 2014 were reviewed. RESULTS: A total of 26 cases, 53% men, had a median age of 33 years (range 2-61). Transplant-associated thrombotic microangiopathy occurred after stem-cell transplant (35%) or solid-organ transplant (65%), frequently associated with the use of cyclosporine or tacrolimus (96%). A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS 13) level was always >10%. After TA-TMA diagnosis, the following drug adjustments were made: discontinuation of cyclosporine or tacrolimus in 45%, dose reduction in another 27%, continuation of the drugs in 23%, and switch from cyclosporine to tacrolimus in remaining 5%. Plasma exchange was performed in ~43%. The median interval between transplant and initiation of eculizumab was 63 days (range 11 512). A median of 5.5 doses (range 2-21) of eculizumab was utilized with 92% response occurring after a median of 2 doses (range 1-18). At a median follow-up of 52 weeks (range 3-113), the survivors (92%) were doing well. CONCLUSION: Within the limits of this retrospective analysis, our study demonstrates that eculizumab use may result in high response rate and 1-year survival in patients with TA-TMA refractory to discontinuation of calcineurin inhibitor and plasma exchange. PMID- 26259913 TI - Thrombin Generation Assay in Hospitalized Nonsurgical Patients: A New Tool to Assess Venous Thromboembolism Risk? AB - BACKGROUND: Assessment of venous thromboembolism (VTE) risk is important to determine optimal primary prophylaxis in hospitalized patients. The Padua score helps to recognize patients with high VTE risk, but quantifying a VTE risk is often challenging in medical patients. Thrombin generation assay (TGA) reflects the pro-/anticoagulant balance and thus could help to better quantify VTE risk in medical hospitalized patients. AIM: To analyze the relation between TGA and VTE risk according to Padua score in medical hospitalized patients. METHODS: Between May and October 2013, 105 patients were included in an unselected cohort group of patients admitted to an internal medicine department in a large, university hospital. Within the 36 hours after admission and before any anticoagulant therapy, Padua score was calculated and sample for TGA was collected for each patient. Thrombin generation assay (velocity, peak, and endogenous thrombin potential [ETP]) was performed with 1 and 5 picomol/l (pM) tissue factor (TF) reagent. RESULTS: In patients with high Padua score (n = 29), velocity, peak, and ETP differed from patients with low Padua score. This difference was present at 1 and 5 pM TF, in ETP (P < .0001 and P = .003 respectively), in peak (P < .0001 in both conditions), and in velocity (P < .0001). According to multivariate analysis, myeloid disorders, older age, higher body mass index, myocardial infarction, C-reactive protein >5 mg/L, reduced mobility with bed rest significantly increased velocity 1 pM TF value. CONCLUSION: Single thrombin generation measurement could help to identify patients at risk of VTE in medical hospitalized patients. PMID- 26259914 TI - NFI-A disrupts myeloid cell differentiation and maturation in septic mice. AB - Mounting evidence supports that sepsis-associated immunosuppression increases mortality. As potential contributors to poor sepsis outcomes, myeloid-derived suppressor cells, which are Gr1(+) CD11b(+) innate-immune cell progenitors unable to differentiate and possess suppressive activities, expand dramatically in septic mice by a process requiring increased microRNA-21 and microRNA-181b expression. The inhibition of these microRNAs in vivo in septic mice restores Gr1(+) CD11b(+) cell differentiation and maturation and improves survival. Here, we show that during sepsis-induced generation of myeloid-derived suppressor cells, transcription factor nuclear factor 1 A type represses cyclin-dependent kinase inhibitor p21 to arrest differentiation of Gr1(+) CD11b(+) cells. Our findings include the following: 1) Gr1(+) CD11b(+) myeloid cells from late septic mice genetically lacking nuclear factor 1 A type cannot suppress CD4(+) T cell proliferation and activation; 2) the reconstitution of nuclear factor 1 A type in microRNA-21 and microRNA-181b-depleted Gr1(+) CD11b(+) myeloid-derived suppressor cells inhibits cyclin-dependent kinase inhibitor p21 and restores the immune suppressor phenotype; 3) ex vivo nuclear factor 1 A type knockdown in Gr1(+) CD11b(+) myeloid-derived suppressor cells from late septic mice restores cyclin dependent kinase inhibitor p21 expression and promotes monocyte and dendritic cell differentiation; and 4) ectopic nuclear factor 1 A type expression in normal Gr1(+) CD11b(+) cells generates an immunosuppressive phenotype. We suggest that therapeutically targeting nuclear factor 1 A type during late sepsis might improve survival. PMID- 26259916 TI - Erratum to: Regulation of density of functional presynaptic terminals by local energy supply. PMID- 26259915 TI - Use of endobronchial valve insertion to treat relapsing pneumothorax: a case report and literature review. AB - : Backgorund and Aims: Unidirectional endobronchial valves have recently been shown to be beneficial as treatment for persistent air leaks. This report presents a first case of endobronchial valve implantation to treat relapsing pneumothorax in a Chinese patient, and also presents a review of the literature on the use of one-way valve insertion for the treatment of persistent air leaks. METHODS: The patient did undergo a recent but failed chest tube intervention. By bronchoscopy and using Chartis(r) system measurements, the upper left lobe (including the left apical bronchus) was closed using a catheter. RESULTS: After the expected decrease in airflow following bronchial occlusion, increased air pressure and decreased spilled air were noted; it was concluded that the pneumothorax was located in the left upper lobe. A Zephyr(r) endobronchial valve was placed in the left upper apical bronchus. The health benefits of the procedure were noticed in the following days. CONCLUSION: Our review suggests that the use of endobronchial valves could be used as an effective, minimally invasive, low-risk intervention for patients with pneumothorax that cannot be treated surgically. PMID- 26259917 TI - In situ synthesis of porous array films on a filament induced micro-gap electrode pair and their use as resistance-type gas sensors with enhanced performances. AB - Resistance-type metal-oxide semiconductor gas sensors with high sensitivity and low detection limit have been explored for practical applications. They require both sensing films with high sensitivity to target gases and an appropriate structure of the electrode-equipped substrate to support the sensing films, which is still challenging. In this paper, a new gas sensor of metal-oxide porous array films on a micro-gap electrode pair is designed and implemented by taking ZnO as a model material. First, a micro-gap electrode pair was constructed by sputtering deposition on a filament template, which was used as the sensor's supporting substrate. Then, the sensing film, made up of ZnO porous periodic arrays, was in situ synthesized onto the supporting substrate by a solution-dipping colloidal lithography strategy. The results demonstrated the validity of the strategy, and the as-designed sensor shows a small device-resistance, an enhanced sensing performance with high resolution and an ultralow detection limit. This work provides an alternative method to promote the practical application of resistance type gas sensors. PMID- 26259918 TI - High ROR2 expression in tumor cells and stroma is correlated with poor prognosis in pancreatic ductal adenocarcinoma. AB - RTK-like orphan receptor 2 (ROR2) is overexpressed in several cancers and has tumorigenic activity. However, the expression of ROR2 and its functional and prognostic significance have yet to be evaluated in pancreatic ductal adenocarcinoma (PDAC). Quantitative real-time polymerase chain reaction was used to characterize the expression of ROR2 mRNA in PDAC, corresponding peritumoral tissues, and PDAC cell lines. Immunohistochemical analysis with tissue microarrays was used to evaluate ROR2 expression in PDAC and to investigate the relationship of this expression to clinicopathological factors and prognosis. The expression of ROR2 mRNA and protein was significantly higher in PDAC than in normal pancreatic tissues. High cytoplasmic ROR2 expression in cancer cells was significantly associated with a primary tumor, distant metastasis, and TNM stage, and high stromal ROR2 expression was significantly associated with regional lymph node metastasis and TNM stage. The Kaplan-Meier method and Cox regression analyses showed that high ROR2 expression in tumor cytoplasm or stromal cells was significantly associated with malignant attributes and reduced survival in PDAC. We present strong evidence that ROR2 could be used as an indicator of poor prognosis and could represent a novel therapeutic target for PDAC. PMID- 26259920 TI - A case of severe rhabdomyolysis with minor trauma: Is sickle cell trait to blame? PMID- 26259919 TI - Fluid role boundaries: exploring the contribution of the advanced nurse practitioner to multi-professional palliative care. AB - AIMS AND OBJECTIVES: To evaluate the introduction of Advanced Nurse Practitioners in a specialist, multi-professional palliative care context. The objective is to explore the core domains and competencies of the advanced nurse practitioner role in a multi-professional palliative care context. BACKGROUND: New models of health care and service delivery are emerging alongside expanded levels of autonomy, skills and decision-making for nurses and midwives. This has resulted in some confusion in the health service community internationally about the professional role and scope of the advanced nurse practitioner. DESIGN: A qualitative evaluation study (n = 21). METHODS: Three phases of data collection were conducted over 10 months. Twenty-one participants took part from a specialist palliative care unit in one health board in a U.K. region spanning ANPs (n = 2) multi-professional staff (n = 14) and patients/carers (n = 5). Data collection methods included individual and focus group interviews with key stakeholders and observation of the advanced nurse practitioners at work and their reflexive diaries. RESULTS: The findings of this evaluation demonstrate that if the advanced nurse practitioner role can flourish it has the potential to shape 'new identities', re-construct the boundaries of nursing roles and emphasise the relationship based elements of excellent nursing work. CONCLUSIONS: The advanced nurse practitioner has the potential to enhance specialist palliative care service delivery through fluid role boundaries. The context in which advanced nurse practitioner roles are developed is important as acceptance of the role is linked to the co-construction of a different nursing identity. Our findings support the need to define, defend and name the work of advanced nursing roles. RELEVANCE TO CLINICAL PRACTICE: The advanced nurse practitioner roles were regarded as providing a unique contribution to service delivery and were characterised by fluid role boundaries which crossed the traditional disciplinary boundaries between nursing and medicine. PMID- 26259921 TI - Streptococcus gallolyticus (bovis): a rare presentation of meningitis in the ED. AB - Bacterial meningitis is a fairly common and often deadly manifestation of altered mental status in the elderly, carrying a mortality rate of greater than 20% despite antibiotic therapy. Most commonly caused by Streptococcus pneumoniae, Listeria monocytogenes, Escherichia coli, and Klebsiella pneumoniae. We present a case of meningitis caused by Streptococcus gallolyticus in an elderly, otherwise healthy woman. There have been no reports in the emergency medicine literature and only a few reports in the literature of S gallolyticus as a cause of altered mental status and meningitis, specifically of immunocompetent patients. PMID- 26259922 TI - Reduction in mRNA and protein expression of a nicotinic acetylcholine receptor alpha8 subunit is associated with resistance to imidacloprid in the brown planthopper, Nilaparvata lugens. AB - Target-site resistance is commonly caused by qualitative changes in insecticide target-receptors and few studies have implicated quantitative changes in insecticide targets in resistance. Here we show that resistance to imidacloprid in a selected strain of Nilaparvata lugens is associated with a reduction in expression levels of the nicotinic acetylcholine receptor (nAChR) subunit Nlalpha8. Synergism bioassays of the selected strain suggested resistance was conferred, in part, by a target-site mechanism. Sequencing of N. lugens nAChR subunit genes identified no mutations associated with resistance, however, a decrease in mRNA and protein levels of Nlalpha8 was observed during selection. RNA interference knockdown of Nlalpha8 decreased the sensitivity of N. lugens to imidacloprid, demonstrating that a decrease in Nlalpha8 expression is sufficient to confer resistance in vivo. Radioligand binding assays revealed that the affinity of the high-affinity imidacloprid-binding site of native nAChRs was reduced by selection, and reducing the amount of Nlalpha8 cRNA injected into Xenopus oocytes significantly decreased imidacloprid potency on recombinant receptors. Taken together, these results provide strong evidence that a decrease in Nlalpha8 levels confers resistance to imidacloprid in N. lugens, and thus provides a rare example of target-site resistance associated with a quantitative rather than qualitative change. In insects, target-site mutations often cause high resistance to insecticides, such as neonicotinoids acting on nicotinic acetylcholine receptors (nAChRs). Here we found that a quantitative change in target-protein level, decrease in mRNA and protein levels of Nlalpha8, contributed importantly to imidacloprid resistance in Nilaparvata lugens. This finding provides a new target-site mechanism of insecticide resistance. PMID- 26259923 TI - Physical Properties, Volatiles Compositions and Sensory Descriptions of the Aromatized Hazelnut Oil-Wax Organogels. AB - The purpose of this study was to determine the physicochemical, thermal and sensorial features of vitamin enriched and aromatized hazelnut oil-beeswax and sunflower wax organogels. Another objective was to monitor the influence of storage on textural and oxidative stability and volatile composition of the organogels. The results show that organogels with beeswax had lower levels of solid fat content, melting point and firmness than sunflower wax counterparts. The microphotographs revealed that beeswax organogels had spherical crystals while sunflower wax organogels continued need-like crystals, but both organogels continued crystallized beta' polymorph. All organogels maintained their oxidative stability during storage. Quantitative descriptive analysis results were consistent with these findings that the organogel structure and properties were similar to breakfast margarine. The main volatile components of the organogels with added strawberry aroma were ethyl acetate, ethyl butanoate, ethyl-2-methyl butanoate, D-limonene, ethyl caproate; banana-aroma were isoamyl acetate, isoamyl valerianate, ethyl acetate; and butter-aroma were 2,3-butanedione, 3-hydroxy-2 butanone. These volatile components were not only detected in the fresh samples but also at the end of the storage period. Sensory definition terms were matched with the sensory descriptors of the detected volatiles. In conclusion, the new organogels were shown to be suitable for food product applications. PMID- 26259924 TI - An advanced draft genome assembly of a desi type chickpea (Cicer arietinum L.). AB - Chickpea (Cicer arietinum L.) is an important pulse legume crop. We previously reported a draft genome assembly of the desi chickpea cultivar ICC 4958. Here we report an advanced version of the ICC 4958 genome assembly (version 2.0) generated using additional sequence data and an improved genetic map. This resulted in 2.7-fold increase in the length of the pseudomolecules and substantial reduction of sequence gaps. The genome assembly covered more than 94% of the estimated gene space and predicted the presence of 30,257 protein-coding genes including 2230 and 133 genes encoding potential transcription factors (TF) and resistance gene homologs, respectively. Gene expression analysis identified several TF and chickpea-specific genes with tissue-specific expression and displayed functional diversification of the paralogous genes. Pairwise comparison of pseudomolecules in the desi (ICC 4958) and the earlier reported kabuli (CDC Frontier) chickpea assemblies showed an extensive local collinearity with incongruity in the placement of large sequence blocks along the linkage groups, apparently due to use of different genetic maps. Single nucleotide polymorphism (SNP)-based mining of intra-specific polymorphism identified more than four thousand SNPs differentiating a desi group and a kabuli group of chickpea genotypes. PMID- 26259926 TI - Relationship between vapor intrusion and human exposure to trichloroethylene. AB - Trichloroethylene (TCE) in groundwater has the potential to volatilize through soil into indoor air where it can be inhaled. The purpose of this study was to determine whether individuals living above TCE-contaminated groundwater are exposed to TCE through vapor intrusion. We examined associations between TCE concentrations in various environmental media and TCE concentrations in residents. For this assessment, indoor air, outdoor air, soil gas, and tap water samples were collected in and around 36 randomly selected homes; blood samples were collected from 63 residents of these homes. Additionally, a completed exposure survey was collected from each participant. Environmental and blood samples were analyzed for TCE. Mixed model multiple linear regression analyses were performed to determine associations between TCE in residents' blood and TCE in indoor air, outdoor air, and soil gas. Blood TCE concentrations were above the limit of quantitation (LOQ; >= 0.012 ug L(-1)) in 17.5% of the blood samples. Of the 36 homes, 54.3%, 47.2%, and >84% had detectable concentrations of TCE in indoor air, outdoor air, and soil gas, respectively. Both indoor air and soil gas concentrations were statistically significantly positively associated with participants' blood concentrations (P = 0.0002 and P = 0.04, respectively). Geometric mean blood concentrations of residents from homes with indoor air concentrations of >1.6 ug m(-3) were approximately 50 times higher than geometric mean blood TCE concentrations in participants from homes with no detectable TCE in indoor air (P < .0001; 95% CI 10.4-236.4). This study confirms the occurrence of vapor intrusion and demonstrates the magnitude of exposure from vapor intrusion of TCE in a residential setting. PMID- 26259925 TI - The DTI Challenge: Toward Standardized Evaluation of Diffusion Tensor Imaging Tractography for Neurosurgery. AB - BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) tractography reconstruction of white matter pathways can help guide brain tumor resection. However, DTI tracts are complex mathematical objects and the validity of tractography-derived information in clinical settings has yet to be fully established. To address this issue, we initiated the DTI Challenge, an international working group of clinicians and scientists whose goal was to provide standardized evaluation of tractography methods for neurosurgery. The purpose of this empirical study was to evaluate different tractography techniques in the first DTI Challenge workshop. METHODS: Eight international teams from leading institutions reconstructed the pyramidal tract in four neurosurgical cases presenting with a glioma near the motor cortex. Tractography methods included deterministic, probabilistic, filtered, and global approaches. Standardized evaluation of the tracts consisted in the qualitative review of the pyramidal pathways by a panel of neurosurgeons and DTI experts and the quantitative evaluation of the degree of agreement among methods. RESULTS: The evaluation of tractography reconstructions showed a great interalgorithm variability. Although most methods found projections of the pyramidal tract from the medial portion of the motor strip, only a few algorithms could trace the lateral projections from the hand, face, and tongue area. In addition, the structure of disagreement among methods was similar across hemispheres despite the anatomical distortions caused by pathological tissues. CONCLUSIONS: The DTI Challenge provides a benchmark for the standardized evaluation of tractography methods on neurosurgical data. This study suggests that there are still limitations to the clinical use of tractography for neurosurgical decision making. PMID- 26259927 TI - Impact of adherence to WHO infant feeding recommendations on later risk of obesity and non-communicable diseases: systematic review. AB - Adherence to WHO infant feeding recommendations has short-term benefits and may also help in the prevention of non-communicable diseases (NCDs). This study reviewed the evidence on whether adherence to all elements of the WHO infant feeding recommendations (comparison group those exclusively breastfed to 6 months, introduced to appropriate complementary feeding from 6 months, with continued breastfeeding to at least 24 months; exposure group characterised by non-adherence to any of the three recommendations) is associated with reduced risk of later obesity or cardiometabolic disease. The population of interest was children not classified as very low weight (weight-for-age z-score >-3.0). MEDLINE, EMBASE, Global Health, CINAHL plus, ProQuest Dissertations and Thesis were systematically searched from 2001 to July 2014, manual reference searching of a birth cohort register (http://www.birthcohorts.net/) as well as papers identified in the search and selected journals was carried out. The database search yielded 9050 records, 275 English-language full-text articles were screened, but no studies were eligible, failing to meet the following criteria: comparison (213); exposure (14); population (3); relevant outcome (5); outcome before 24 months (9); insufficient information provided (30); plus one study was qualitative. Eight studies met the inclusion criterion of exclusive breastfeeding to 6 months, but did not meet the other inclusion criteria. The present study has revealed an important gap in the evidence on NCD prevention, and suggestions for addressing this evidence gap are provided. PMID- 26259928 TI - Activin suppresses LPS-induced Toll-like receptor, cytokine and inducible nitric oxide synthase expression in normal human melanocytes by inhibiting NF-kappaB and MAPK pathway activation. AB - Activins are dimeric growth and differentiation factors that belong to the transforming growth factor (TGF)-beta superfamily of structurally related signaling proteins. In the present study, we examined the mechanisms through which activin regulates the lipopolysaccharide (LPS)-induced transcription of Toll-like receptors (TLRs), cytokines and inducible nitric oxide synthase (iNOS) in human melanocytes, as well as the involvement of nuclear factor (NF)-kappaB and mitogen-activated protein kinase (MAPK) signaling. Cell proliferation was analyzed by cell viability assay, mRNA expression was detected by RT-qPCR, and protein expression was measured by western blot analysis. LPS increased the mRNA expression of TLRs (TLR1-10) and cytokines [interleukin (IL)-1beta, IL-6, IL-8 and TNF-alpha], as well as the mRNA and protein expression of iNOS. Activin decreased the LPS-induced TLR and cytokine mRNA expression, as well as the LPS induced iNOS mRNA and protein expression. In addition, activin suppressed NF kappaB p65 activation and blocked inhibitor of NF-kappaB (IkappaBalpha) degradation in LPS-stimulated melanocytes, and reduced LPS-induced p38 MAPK and MEK/ERK activation. On the whole, our results demonstrated that activin inhibited TLR and cytokine expression in LPS-activated normal human melanocytes and suppressed LPS-induced iNOS gene expression. Moreover, the anti-inflammatory effects of activin were shown to be mediated through the suppression of NF-kappaB and MAPK signaling, resulting in reduced TLR and iNOS expression, and in the inhibition of inflammatory cytokine expression. PMID- 26259929 TI - Battling the spread: Herpes simplex virus and encephalitis. PMID- 26259930 TI - omega-Amidase: an underappreciated, but important enzyme in L-glutamine and L asparagine metabolism; relevance to sulfur and nitrogen metabolism, tumor biology and hyperammonemic diseases. AB - In mammals, two major routes exist for the metabolic conversion of L-glutamine to alpha-ketoglutarate. The most widely studied pathway involves the hydrolysis of L glutamine to L-glutamate catalyzed by glutaminases, followed by the conversion of L-glutamate to alpha-ketoglutarate by the action of an L-glutamate-linked aminotransferase or via the glutamate dehydrogenase reaction. However, another major pathway exists in mammals for the conversion of L-glutamine to alpha ketoglutarate (the glutaminase II pathway) in which L-glutamine is first transaminated to alpha-ketoglutaramate (KGM) followed by hydrolysis of KGM to alpha-ketoglutarate and ammonia catalyzed by an amidase known as omega-amidase. In mammals, the glutaminase II pathway is present in both cytosolic and mitochondrial compartments and is most prominent in liver and kidney. Similarly, two routes exist for the conversion of L-asparagine to oxaloacetate. In the most extensively studied pathway, L-asparagine is hydrolyzed to L-aspartate by the action of asparaginase, followed by transamination of L-aspartate to oxaloacetate. However, another pathway also exists for the conversion of L asparagine to oxaloacetate (the asparaginase II pathway). In this pathway, L asparagine is first transaminated to alpha-ketosuccinamate (KSM), followed by hydrolysis of KSM to oxaloacetate by the action of omega-amidase. One advantage of both the glutaminase II and the asparaginase II pathways is that they are irreversible, and thus are important in anaplerosis by shuttling 5-C (alpha ketoglutarate) and 4-C (oxaloacetate) units into the TCA cycle. In this review, we briefly mention the importance of the glutaminase II and asparaginase II pathways in microorganisms and plants. However, the major emphasis of the review is related to the importance of these pathways (especially the common enzyme component of both pathways--omega-amidase) in nitrogen and sulfur metabolism in mammals and as a source of anaplerotic carbon moieties in rapidly dividing cells. The review also discusses a potential dichotomous function of omega-amidase as having a role in tumor progression. Finally, the possible role of KGM as a biomarker for hyperammonemic diseases is discussed. PMID- 26259931 TI - Detection and Genetic Characterization of Lineage IV Peste Des Petits Ruminant Virus in Kazakhstan. AB - Peste des petits ruminant (PPR) is endemic in many Asian countries with expansion of the range in recent years including across China during 2013-2014 (OIE, 2014). Till the end of 2014, no cases of PPR virus (PPRV) were officially reported to the Office Internationale des Epizooties (OIE) from Kazakhstan. This study describes for the first time clinicopathological, epidemiological and genetic characterization of PPRV in 3 farm level outbreaks reported for the first time in Zhambyl region (oblast), southern Kazakhstan. Phylogenetic analysis based on partial N gene sequence data confirms the lineage IV PPRV circulation, similar to the virus that recently circulated in China. The isolated viruses are 99.5-99.7% identical to the PPRV isolated in 2014 from Heilongjiang Province in China and therefore providing evidence of transboundary spread of PPRV. There is a risk of further maintenance of virus in young stock despite vaccination of adult sheep and goats, along livestock trade and pastoral routes, threatening both small livestock and endangered susceptible wildlife populations throughout Kazakhstan. PMID- 26259932 TI - How we define hyponatraemia? PMID- 26259933 TI - Atrial fibrillation. Adenosine testing during catheter ablation of AF reduces recurrent atrial tachyarrhythmia. PMID- 26259934 TI - Recurrent pericarditis: new and emerging therapeutic options. AB - Recurrent pericarditis is one of the most common and troublesome complications after an episode of pericarditis, and affects 20-50% of patients treated for pericarditis. In most of these patients, the pericarditis remains idiopathic, although an immune-mediated (either autoimmune or autoinflammatory) pathogenesis is often presumed. The mainstay of therapy for recurrences is aspirin or NSAIDs, with the adjunct of colchicine. Corticosteroids are a second-line option to be considered for specific indications, such as connective tissue disease or pregnancy; contraindications or intolerance to aspirin, NSAIDs, and/or colchicine; or insufficient response to these medications. Furthermore, corticosteroids can be added to NSAIDs and colchicine in patients with persistent symptoms. In patients who do not respond adequately to any of these conventional therapies, alternative treatment options include azathioprine, intravenous human immunoglobulins, and anakinra. An improved understanding of how recurrent pericarditis develops after an initiating event is critical to prevent this complication, and further research is needed into the pathogenesis of recurrences. We discuss the aetiology and diagnosis of recurrent pericarditis, and extensively review the treatment options for this condition. PMID- 26259936 TI - Aortic disease: Endovascular vs. open AAA repair. PMID- 26259935 TI - Mast cells in human and experimental cardiometabolic diseases. AB - Mast cells, like many other types of inflammatory cell, perform pleiotropic roles in cardiometabolic diseases such as atherosclerosis, abdominal aortic aneurysms, obesity, and diabetes mellitus, as well as complications associated with these diseases. Low numbers of mast cells are present in the heart, aorta, and adipose tissue of healthy humans, but patients with cardiometabolic diseases and animals with experimentally-induced cardiometabolic pathologies have high numbers of mast cells with increased activity in the affected tissues. Mediators released by the activated mast cells, such as chemokines, cytokines, growth factors, heparin, histamine, and proteases, not only function as biomarkers of cardiometabolic diseases, but might also directly contribute to the pathogenesis of such diseases. Mast-cell mediators impede the functions of vascular cells, the integrity of the extracellular matrix, and the activity of other inflammatory cells, thereby contributing to the pathobiology of the conditions at multiple levels. In mouse models, mast-cell activation aggravates the progression of various cardiometabolic pathologies, whereas a genetic deficiency or pharmacological stabilization of mast cells, or depletion or inhibition of specific mast-cell mediators, tends to delay the progression of such conditions. Pharmacological inhibition of mast-cell activation or their targeted effector functions offers potential novel therapeutic strategies for patients with cardiometabolic disorders. PMID- 26259937 TI - Malaria Diagnosis Across the International Centers of Excellence for Malaria Research: Platforms, Performance, and Standardization. AB - Diagnosis is "the act of identifying a disease, illness, or problem by examining someone or something." When an individual with acute fever presents for clinical attention, accurate diagnosis leading to specific, prompt treatment often saves lives. As applied to malaria, not only individual patient diagnosis is important but also assessing population-level malaria prevalence using appropriate diagnostic methods is essential for public health purposes. Similarly, identifying (diagnosing) fake antimalarial medications prevents the use of counterfeit drugs that can have disastrous effects. Therefore, accurate diagnosis in broad areas related to malaria is fundamental to improving health-care delivery, informing funding agencies of current malaria situations, and aiding in the prioritization of regional and national control efforts. The International Centers of Excellence for Malaria Research (ICEMR), supported by the U.S. National Institute of Allergy and Infectious Diseases, has collaborated on global efforts to improve malaria diagnostics by working to harmonize and systematize procedures across different regions where endemicity and financial resources vary. In this article, the different diagnostic methods used across each ICEMR are reviewed and challenges are discussed. PMID- 26259938 TI - Biosignatures of Exposure/Transmission and Immunity. AB - A blood test that captures cumulative exposure over time and assesses levels of naturally acquired immunity (NAI) would provide a critical tool to monitor the impact of interventions to reduce malaria transmission and broaden our understanding of how NAI develops around the world as a function of age and exposure. This article describes a collaborative effort in multiple International Centers of Excellence in Malaria Research (ICEMRs) to develop such tests using malaria-specific antibody responses as biosignatures of transmission and immunity. The focus is on the use of Plasmodium falciparum and Plasmodium vivax protein microarrays to identify a panel of the most informative antibody responses in diverse malaria-endemic settings representing an unparalleled spectrum of malaria transmission and malaria species mixes before and after interventions to reduce malaria transmission. PMID- 26259939 TI - Investigating the Pathogenesis of Severe Malaria: A Multidisciplinary and Cross Geographical Approach. AB - More than a century after the discovery of Plasmodium spp. parasites, the pathogenesis of severe malaria is still not well understood. The majority of malaria cases are caused by Plasmodium falciparum and Plasmodium vivax, which differ in virulence, red blood cell tropism, cytoadhesion of infected erythrocytes, and dormant liver hypnozoite stages. Cerebral malaria coma is one of the most severe manifestations of P. falciparum infection. Insights into its complex pathophysiology are emerging through a combination of autopsy, neuroimaging, parasite binding, and endothelial characterizations. Nevertheless, important questions remain regarding why some patients develop life-threatening conditions while the majority of P. falciparum-infected individuals do not, and why clinical presentations differ between children and adults. For P. vivax, there is renewed recognition of severe malaria, but an understanding of the factors influencing disease severity is limited and remains an important research topic. Shedding light on the underlying disease mechanisms will be necessary to implement effective diagnostic tools for identifying and classifying severe malaria syndromes and developing new therapeutic approaches for severe disease. This review highlights progress and outstanding questions in severe malaria pathophysiology and summarizes key areas of pathogenesis research within the International Centers of Excellence for Malaria Research program. PMID- 26259940 TI - Population Genetics, Evolutionary Genomics, and Genome-Wide Studies of Malaria: A View Across the International Centers of Excellence for Malaria Research. AB - The study of the three protagonists in malaria-the Plasmodium parasite, the Anopheles mosquito, and the human host-is key to developing methods to control and eventually eliminate the disease. Genomic technologies, including the recent development of next-generation sequencing, enable interrogation of this triangle to an unprecedented level of scrutiny, and promise exciting progress toward real time epidemiology studies and the study of evolutionary adaptation. We discuss the use of genomics by the International Centers of Excellence for Malaria Research, a network of field sites and laboratories in malaria-endemic countries that undertake cutting-edge research, training, and technology transfer in malarious countries of the world. PMID- 26259941 TI - Urban Malaria: Understanding its Epidemiology, Ecology, and Transmission Across Seven Diverse ICEMR Network Sites. AB - A major public health question is whether urbanization will transform malaria from a rural to an urban disease. However, differences about definitions of urban settings, urban malaria, and whether malaria control should differ between rural and urban areas complicate both the analysis of available data and the development of intervention strategies. This report examines the approach of the International Centers of Excellence for Malaria Research (ICEMR) to urban malaria in Brazil, Colombia, India (Chennai and Goa), Malawi, Senegal, and Uganda. Its major theme is the need to determine whether cases diagnosed in urban areas were imported from surrounding rural areas or resulted from transmission within the urban area. If infections are being acquired within urban areas, malaria control measures must be targeted within those urban areas to be effective. Conversely, if malaria cases are being imported from rural areas, control measures must be directed at vectors, breeding sites, and infected humans in those rural areas. Similar interventions must be directed differently if infections were acquired within urban areas. The hypothesis underlying the ICEMR approach to urban malaria is that optimal control of urban malaria depends on accurate epidemiologic and entomologic information about transmission. PMID- 26259942 TI - Entomological Monitoring and Evaluation: Diverse Transmission Settings of ICEMR Projects Will Require Local and Regional Malaria Elimination Strategies. AB - The unprecedented global efforts for malaria elimination in the past decade have resulted in altered vectorial systems, vector behaviors, and bionomics. These changes combined with increasingly evident heterogeneities in malaria transmission require innovative vector control strategies in addition to the established practices of long-lasting insecticidal nets and indoor residual spraying. Integrated vector management will require focal and tailored vector control to achieve malaria elimination. This switch of emphasis from universal coverage to universal coverage plus additional interventions will be reliant on improved entomological monitoring and evaluation. In 2010, the National Institutes for Allergies and Infectious Diseases (NIAID) established a network of malaria research centers termed ICEMRs (International Centers for Excellence in Malaria Research) expressly to develop this evidence base in diverse malaria endemic settings. In this article, we contrast the differing ecology and transmission settings across the ICEMR study locations. In South America, Africa, and Asia, vector biologists are already dealing with many of the issues of pushing to elimination such as highly focal transmission, proportionate increase in the importance of outdoor and crepuscular biting, vector species complexity, and "sub patent" vector transmission. PMID- 26259944 TI - A Framework for Global Collaborative Data Management for Malaria Research. AB - Data generated during the course of research activities carried out by the International Centers of Excellence for Malaria Research (ICEMR) is heterogeneous, large, and multi-scaled. The complexity of federated and global data operations and the diverse uses planned for the data pose tremendous challenges and opportunities for collaborative research. In this article, we present the foundational principles for data management across the ICEMR Program, the logistics associated with multiple aspects of the data life cycle, and describe a pilot centralized web information system created in PlasmoDB to query a subset of this data. The paradigm proposed as a solution for the data operations in the ICEMR Program is widely applicable to large, multifaceted research projects, and could be reproduced in other contexts that require sophisticated data management. PMID- 26259945 TI - Malaria Molecular Epidemiology: Lessons from the International Centers of Excellence for Malaria Research Network. AB - Molecular epidemiology leverages genetic information to study the risk factors that affect the frequency and distribution of malaria cases. This article describes molecular epidemiologic investigations currently being carried out by the International Centers of Excellence for Malaria Research (ICEMR) network in a variety of malaria-endemic settings. First, we discuss various novel approaches to understand malaria incidence and gametocytemia, focusing on Plasmodium falciparum and Plasmodium vivax. Second, we describe and compare different parasite genotyping methods commonly used in malaria epidemiology and population genetics. Finally, we discuss potential applications of molecular epidemiological tools and methods toward malaria control and elimination efforts. PMID- 26259943 TI - Antimalarial Drug Resistance: Literature Review and Activities and Findings of the ICEMR Network. AB - Antimalarial drugs are key tools for the control and elimination of malaria. Recent decreases in the global malaria burden are likely due, in part, to the deployment of artemisinin-based combination therapies. Therefore, the emergence and potential spread of artemisinin-resistant parasites in southeast Asia and changes in sensitivities to artemisinin partner drugs have raised concerns. In recognition of this urgent threat, the International Centers of Excellence for Malaria Research (ICEMRs) are closely monitoring antimalarial drug efficacy and studying the mechanisms underlying drug resistance. At multiple sentinel sites of the global ICEMR network, research activities include clinical studies to track the efficacies of antimalarial drugs, ex vivo/in vitro assays to measure drug susceptibilities of parasite isolates, and characterization of resistance mediating parasite polymorphisms. Taken together, these efforts offer an increasingly comprehensive assessment of the efficacies of antimalarial therapies, and enable us to predict the emergence of drug resistance and to guide local antimalarial drug policies. Here we briefly review worldwide antimalarial drug resistance concerns, summarize research activities of the ICEMRs related to drug resistance, and assess the global impacts of the ICEMR programs. PMID- 26259946 TI - Malaria Epidemiology and Control Within the International Centers of Excellence for Malaria Research. AB - Understanding the epidemiological features and metrics of malaria in endemic populations is a key component to monitoring and quantifying the impact of current and past control efforts to inform future ones. The International Centers of Excellence for Malaria Research (ICEMR) has the opportunity to evaluate the impact of malaria control interventions across endemic regions that differ in the dominant Plasmodium species, mosquito vector species, resistance to antimalarial drugs and human genetic variants thought to confer protection from infection and clinical manifestations of plasmodia infection. ICEMR programs are conducting field studies at multiple sites with the aim of generating standardized surveillance data to improve the understanding of malaria transmission and to monitor and evaluate the impact of interventions to inform malaria control and elimination programs. In addition, these epidemiological studies provide a vast source of biological samples linked to clinical and environmental "meta-data" to support translational studies of interactions between the parasite, human host, and mosquito vector. Importantly, epidemiological studies at the ICEMR field sites are integrated with entomological studies, including the measurement of the entomological inoculation rate, human biting index, and insecticide resistance, as well as studies of parasite genetic diversity and antimalarial drug resistance. PMID- 26259948 TI - The hour-to-hour influence of weather conditions on walking and cycling among Dutch older adults. AB - BACKGROUND: physical activity (PA) is an important factor to promote healthy ageing. However, older adults are not physically active enough. Socio-ecological models suggest that weather conditions are determinants of PA and may bias relations between other environmental factors and PA. This may especially be the case for the most vulnerable and inactive older persons. Understanding the role of weather conditions is based on daily or seasonal variation in weather, but it can be improved by using hour-to-hour measured weather conditions. PURPOSE: to study the hour-to-hour relationships between weather factors and objectively measured walking and cycling in a sample of Dutch older adults. METHODS: baseline data (2013) of a sub-sample of older adults (3,248 observations clustered in 43 adults) participating in The Neighborhood Walking in Rotterdam Older ADultS (NEW.ROADS) trial were used. Participants wore a GPS logger for 7 consecutive days. Hour-to-hour weather data (temperature, wind speed, rain and sun time) for the city of Rotterdam were retrieved from the Royal Netherlands Meteorological Institute. Multilevel linear regression models were fitted with minutes walked and minutes cycled as dependent variables and the weather variables as independent variables. RESULTS: the time older adults walked increased with higher temperature, higher wind speed and the absence of rain. The time cycled increased with higher temperature. CONCLUSIONS: this study improves the evidence of weather factors as a determinant for walking and cycling in older adults. Studies on the relation between environmental factors and PA should consider adjustment for weather factors. PMID- 26259947 TI - Insecticide Resistance in Areas Under Investigation by the International Centers of Excellence for Malaria Research: A Challenge for Malaria Control and Elimination. AB - Scale-up of the main vector control interventions, residual insecticides sprayed on walls or structures and/or impregnated in bed nets, together with prompt diagnosis and effective treatment, have led to a global reduction in malaria transmission. However, resistance in vectors to almost all classes of insecticides, particularly to the synthetic pyrethroids, is posing a challenge to the recent trend of declining malaria. Ten International Centers of Excellence for Malaria Research (ICEMR) located in the most malaria-endemic regions of the world are currently addressing insecticide resistance in the main vector populations, which not only threaten hope for elimination in malaria-endemic countries but also may lead to reversal where notable reductions in malaria have been documented. This communication illustrates the current status of insecticide resistance with a focus on the countries where activities are ongoing for 9 out of the 10 ICEMRs. Most of the primary malaria vectors in the ICEMR countries exhibit insecticide resistance, albeit of varying magnitude, and spanning all mechanisms of resistance. New alternatives to the insecticides currently available are still to be fully developed for deployment. Integrated vector management principles need to be better understood and encouraged, and viable insecticide resistance management strategies need to be developed and implemented. PMID- 26259949 TI - Depression: to screen or not to screen? PMID- 26259950 TI - Epidural abscess after dental extraction. PMID- 26259951 TI - Can metabotyping help deliver the promise of personalised nutrition? AB - Over a decade since the completion of the human genome sequence, the promise of personalised nutrition available to all has yet to become a reality. While the definition was originally very gene-focused, in recent years, a model of personalised nutrition has emerged with the incorporation of dietary, phenotypic and genotypic information at various levels. Developing on from the idea of personalised nutrition, the concept of targeted nutrition has evolved which refers to the delivery of tailored dietary advice at a group level rather than at an individual level. Central to this concept is metabotyping or metabolic phenotyping, which is the ability to group similar individuals together based on their metabolic or phenotypic profiles. Applications of the metabotyping concept extend from the nutrition to the medical literature. While there are many examples of the metabotype approach, there is a dearth in the literature with regard to the development of tailored interventions for groups of individuals. This review will first explore the effectiveness of personalised nutrition in motivating behaviour change and secondly, examine potential novel ways for the delivery of personalised advice at a population level through a metabotyping approach. Based on recent findings from our work, we will demonstrate a novel strategy for the delivery of tailored dietary advice at a group level using this concept. In general, there is a strong emerging evidence to support the effectiveness of personalised nutrition; future work should ascertain if targeted nutrition can motivate behaviour change in a similar manner. PMID- 26259953 TI - Outcome of a reproductive health advocacy mentoring intervention for staff of selected non-governmental organisations in Nigeria. AB - BACKGROUND: Non-governmental organisations (NGOs) are expected to be in the vanguard, repositioning reproductive health as a central issue in population and development in Nigeria. However, most of them have insufficient knowledge or access to policy and planning processes necessary at engaging effectively with the government. This article highlights the processes and outcome of an intervention aimed at strengthening the capacity of 12 non-governmental organisations on advocacy and policy related activities with emphasis on reproductive health issues. METHODS: The study employed a one group, pre and post test study design. Thirty six (36) staff from 12 NGOs was purposively selected and interviewed using a semi-structured questionnaire at baseline to assess their knowledge and level of involvement in reproductive health, advocacy and policy issues. In-depth interviews were conducted with 6 officials of the ministries of health and women affairs to document previous reproductive health and policy related collaborative efforts with the NGOs. Baseline findings were used in developing and implementing a capacity building intervention. A post intervention evaluation was conducted to assess the outcomes. RESULTS: All respondents (100%) had tertiary level education and were from a multidisciplinary background such as nursing (41.7%) medicine (25%) and administration (13.9%). The mean knowledge score on advocacy and policy issues at pre-test and post test was 39.1 +/- 17.6 and 76.2 +/- 14.2 respectively (p = 0.00). Participants reported making use of advocacy methods and the three most utilized were Phone calls (28.1%), Face to Face meetings (26%) and networking with other organisations for stronger impact (17.1%). The outcome of their advocacy efforts include the provision of free air time by a television station to educate the populace on maternal health issues, donation of landed property to build a youth friendly centre, donation of a blog site for disseminating information on Reproductive health issues and training of other staff of their organisations on advocacy activities. The major challenges experienced by staff of the NGOs were financial (89%) and time constraints (11%). CONCLUSION: Empowered non-governmental organisations can effectively advocate for the implementation of reproductive health policies and programmes. PMID- 26259952 TI - The suitability of laboratory-bred Anopheles cracens for the production of Plasmodium vivax sporozoites. AB - BACKGROUND: A stenogamous colony of Anopheles cracens (A. dirus B) established 20 years ago in a Thai insectary proved susceptible to Plasmodium vivax. However, routine sporozoite production by feeding on field-collected blood samples has not been described. The setting-up of an A. cracens colony in an insectary on the Thai-Myanmar border and the process of using P. vivax field samples for the production of infectious sporozoites are described. METHODS: The colony was started in 2012 from egg batches that were sent from the Department of Parasitology, Faculty of Medicine, University of Chiang Mai, to the Shoklo Malaria Research Unit (SMRU), on wet filter paper in sealed Petri dishes. From May 2013 to December 2014, P. vivax-infected blood samples collected from patients seeking care at SMRU clinics were used for membrane feeding assays and sporozoite production. RESULTS: Mosquitoes were fed on blood samples from 55 patients, and for 38 (69 %) this led to the production sporozoites. The average number of sporozoites obtained per mosquito was 26,112 (range 328-79,310). Gametocytaemia was not correlated with mosquito infectiousness (p = 0.82), or with the number of the sporozoites produced (Spearman's rho = -0.016, p = 0.905). Infectiousness did not vary with the date of collection or the age of the patient. Mosquito survival was not correlated with sporozoite load (Spearman's rho = 0.179, p = 0.282). CONCLUSION: Consistent and routine P. vivax sporozoites production confirms that A. cracens is highly susceptible to P. vivax infection. Laboratory-bred colonies of this vector are suitable for experimental transmission protocols and thus constitute a valuable resource. PMID- 26259954 TI - Diagnostic TCD for intracranial stenosis in acute stroke patients: experience from a tertiary care stroke center in Karachi, Pakistan. AB - BACKGROUND: Stroke is a common cause of morbidity and mortality around the world. Intracranial large artery atherosclerosis (ICAD) is a frequent etiology of stroke in the South Asian population. There is a need for widely available screening tools to identify patients that are at high risk of stroke due to ICAD for aggressive risk management. This study describes the experience of using the transcranial Doppler (TCD) as a screening tool for this purpose at a tertiary care hospital in a developing country. METHODS: 86 Patients admitted with stroke due to ICAD underwent TCD for six arteries (Right and left middle cerebral arteries, right and left anterior cerebral arteries, right and left posterior cerebral arteries) in addition to the magnetic resonance angiography (MRA) that is done routinely at the stroke center. Arteries were labeled with either <50 or >50% stenosis by TCD using two separate criteria. These findings were compared with those from the MRA which was used as the gold standard. The proportion of patients that had complete exams (all six arteries insonated by TCD) was reported. The success rate of each TCD criteria in detecting arteries with >50% stenosis was also calculated. RESULTS: There was an attempt to visualize 516 arteries (86 patients with 6 arteries each) of which 375 (72.7%) were successfully insonated. 38 of the 86 (55.8%) patients had complete examinations. MRA reported 43 (8.3%) arteries as stenosed >50%. The TCD did not categorize any artery as stenosed using either criterion and hence failed to classify any stenosed artery correctly. The positive predictive and sensitivity was 0 for this study and the negative predictive value was 93.3%. CONCLUSIONS: This study indicates the poor sensitivity of TCD to be a reliable screening tool for the presence of ICAD in the South Asian population in a real life clinical setting. PMID- 26259956 TI - Impact of Alternative Maternal Demand-Side Financial Support Programs in India on the Caesarean Section Rates: Indications of Supplier-Induced Demand. AB - BACKGROUND: This paper examines two state-led public-private demand-side financial support programs aiming to raise hospital delivery rates in two neighbouring Indian states-Gujarat and Madhya Pradesh. The national Janani Suraksha Yojana (JSY) was complemented with a public-private partnership program Janani Sahayogi Yojana (JSaY) in Madhya Pradesh in which private obstetricians were paid to deliver poor women. A higher amount was paid for caesarean sections (CS) than for vaginal deliveries (VD). In Gujarat state, the state program Chiranjeevi Yojana (CY) paid private obstetricians a fixed amount for a block 100 deliveries irrespective of delivery mode. The two systems thus offered an opportunity to observe the influence of supplier-induced demand (SID) from opposite incentives related to delivery mode. METHODS: The data from the two programs was sourced from the Departments of Health and Family Welfare, Governments of Gujarat and Madhya Pradesh, India. RESULTS: In JSaY program the CS rate increased from 26.6% (2007-2008) to 40.7% (2010-2011), against the background rate for CS in Madhya Pradesh, of only 4.9% (2004-2006). Meanwhile in CY program in Gujarat, the CS rate decreased to 4.3% (2010-2011) against a background CS rate of 8.1% (2004-2006). CONCLUSIONS: The findings from India are unique in that they not only point to a significant impact from the introduction of the financial incentives but also how disincentives have an inverse impact on the choice of delivery method. PMID- 26259955 TI - A phase I/Ib study of trametinib (GSK1120212) alone and in combination with gemcitabine in Japanese patients with advanced solid tumors. AB - BACKGROUND: Trametinib is an inhibitor of MEK1/MEK2 activation and kinase activity. In order to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of single-agent trametinib (part 1) and trametinib in combination with gemcitabine (part 2), we undertook the first clinical study of this combination in Japanese patients with cancer and herein report our results. METHODS: In part 1, 13 patients with advanced solid tumors were enrolled into 3 dose cohorts, receiving trametinib once daily at a dose of 1.0, 2.0, or 3.0 mg. In part 2, 5 patients with pancreatic cancer received trametinib (2.0 mg once daily) in combination with gemcitabine (1000 mg/m(2)). RESULTS: In part 1, a dose limiting toxicity was observed in a patient in the 2.0-mg dose cohort, but the maximum tolerated dose was not reached at doses up to 3.0 mg daily. The best overall response was a PR in 1 patient, and 6 patients had SD. In part 2, the combination of trametinib and gemcitabine was tolerated for a short period of time. However, serious interstitial lung disease (ILD) was observed in 3 of 5 patients 4 weeks or more after the start of the treatment, including 1 fatal case. Three patients achieved a PR, and 2 patients had SD. The most common adverse event was rash (85 % in part 1 and 100 % in part 2). CONCLUSIONS: Trametinib monotherapy was tolerable in Japanese patients with cancer. However, the combination of trametinib plus gemcitabine carried a higher risk as compared with monotherapy, during which no ILD was observed. (ClinicalTrials.gov number, NCT01324258.). PMID- 26259957 TI - Evaluation of two immunodiagnostic tests for early rapid diagnosis of leptospirosis in Sri Lanka: a preliminary study. AB - BACKGROUND: Leptospirosis is often treated based on clinical diagnosis. There is a need for rapid laboratory diagnosis for this condition. The aim of this study was to compare the diagnostic accuracy of two rapid IgM based immunodiagnostic assays with the microscopic agglutination test (MAT), in acute leptospirosis infection. METHODS: MAT, IgM based immunochromatographic test (Leptocheck-WB) and IgM ELISA were performed using acute sera of patients clinically suspected to have leptospirosis (n = 83). Bayesian latent class modeling was used to compare the accuracy of these tests. RESULTS: Percentage positivity for MAT, Leptocheck WB, and IgM ELISA were 48.1, 55.3, and 45.7 % respectively. Bayesian latent class modeling showed a combined positivity rate of leptospirosis of 44.7 %. The sensitivity of MAT, Leptocheck-WB and IgM ELISA were 91.4, 95 and 81.1 %, and specificity were 86.7, 76.4 and 83.1 %, respectively. CONCLUSIONS: Leptocheck-WB has high sensitivity, and, because it is quick and easy to perform, would be a good screening test for acute leptospirosis infection. IgM ELISA has good specificity, and is comparable with MAT; given that it is easier to perform and more widely available than MAT, it would be a more appropriate confirmatory test for use in hospitals with limited access to a specialized laboratory. PMID- 26259958 TI - Guidelines for the Reporting of Treatment Trials for Alcohol Use Disorders. AB - BACKGROUND: The primary goals in conducting clinical trials of treatments for alcohol use disorders (AUDs) are to identify efficacious treatments and determine which treatments are most efficacious for which patients. Accurate reporting of study design features and results is imperative to enable readers of research reports to evaluate to what extent a study has achieved these goals. Guidance on quality of clinical trial reporting has evolved substantially over the past 2 decades, primarily through the publication and widespread adoption of the Consolidated Standards of Reporting Trials statement. However, there is room to improve the adoption of those standards in reporting the design and findings of treatment trials for AUD. METHODS: This paper provides a narrative review of guidance on reporting quality in AUD treatment trials. RESULTS: Despite improvements in the reporting of results of treatment trials for AUD over the past 2 decades, many published reports provide insufficient information on design or methods. CONCLUSIONS: The reporting of alcohol treatment trial design, analysis, and results requires improvement in 4 primary areas: (i) trial registration, (ii) procedures for recruitment and retention, (iii) procedures for randomization and intervention design considerations, and (iv) statistical methods used to assess treatment efficacy. Improvements in these areas and the adoption of reporting standards by authors, reviewers, and editors are critical to an accurate assessment of the reliability and validity of treatment effects. Continued developments in this area are needed to move AUD treatment research forward via systematic reviews and meta-analyses that maximize the utility of completed studies. PMID- 26259960 TI - Magnetoencephalographic Correlates of Emotional Processing in Major Depression Before and After Pharmacological Treatment. AB - BACKGROUND: In major depressive disorder (MDD), electrophysiological and imaging studies suggest reduced neural activity in the parietal and dorsolateral prefrontal cortex regions. In the present study, neural correlates of emotional processing in MDD were analyzed for the first time in a pre-/post-treatment design by means of magnetoencephalography (MEG), allowing for detecting temporal dynamics of brain activation. METHODS: Twenty-five medication-free Caucasian in patients with MDD and 25 matched controls underwent a baseline MEG session with passive viewing of pleasant, unpleasant, and neutral pictures. Fifteen patients were followed-up with a second MEG session after 4 weeks of antidepressant monopharmacotherapy with mirtazapine. The corresponding controls received no intervention between the measurements. The clinical course of depression was assessed using the Hamilton Depression scale. RESULTS: Prior to treatment, an overall neocortical hypoactivation during emotional processing, particularly at the parietal regions and areas at the right temporoparietal junction, as well as abnormal valence-specific reactions at the right parietal and bilateral dorsolateral prefrontal cortex (dlPFC) regions were observed in patients compared to controls. These effects occurred <150 ms, suggesting dysfunctional processing of emotional stimuli at a preconscious level. Successful antidepressant treatment resulted in a normalization of the hypoactivation at the right parietal and right temporoparietal regions. Accordingly, both dlPFC regions revealed an increase of activity after therapy. CONCLUSIONS: The present study provides neurophysiological evidence for dysfunctional emotional processing in a fronto parieto-temporal network, possibly contributing to the pathogenesis of MDD. These activation patterns might have the potential to serve as biomarkers of treatment success. PMID- 26259961 TI - Trace levels of the CHO host cell protease cathepsin D caused particle formation in a monoclonal antibody product. AB - Chinese hamster ovary (CHO) cells are often used to produce therapeutic monoclonal antibodies (mAbs). CHO cells express many host cell proteins (HCPs) required for their growth. Interactions of HCPs with mAbs can sometimes result in co-purification of trace levels of 'hitchhiker' HCPs during the manufacturing process. Purified mAb-1 product produced in early stages of process optimization had high HCP levels. In addition, these lots formed delayed-onset particles containing mAb-1 and its heavy chain C-terminal fragments. Studies were performed to determine the cause of the observed particle formation and to optimize the purification for improved HCP clearance. Protease activity and inhibitor stability studies confirmed that an aspartyl protease was responsible for fragmentation of mAb-1 resulting in particle formation. An affinity resin was used to selectively capture aspartyl proteases from the mAb-1 product. Mass spectrometry identified the captured aspartyl protease as CHO cathepsin D. A wash step at high pH with salt and caprylate was implemented during the protein A affinity step to disrupt the HCP-mAb interactions and improve HCP clearance. The product at the end of purification using the optimized process had very low HCP levels, did not contain detectable protease activity, and did not form particles. Spiking of CHO cathepsin D back into mAb-1 product from the optimized process confirmed that it was the cause of the particle formation. This work demonstrated that process optimization focused on removal of HCPs was successful in eliminating particle formation in the final mAb-1 product. PMID- 26259962 TI - Cancer-associated fibroblasts as target and tool in cancer therapeutics and diagnostics. AB - Cancer-associated fibroblasts (CAFs) are drivers of tumour progression and are considered as a target and a tool in cancer diagnostic and therapeutic applications. An increased abundance of CAFs or CAF signatures are recognized as a bad prognostic marker in several cancer types. Tumour-environment biomimetics strongly improve our understanding of the communication between CAFs, cancer cells and other host cells. Several experimental drugs targeting CAFs are in clinical trials for multiple tumour entities; alternatively, CAFs can be exploited as a tool to characterize the functionality of circulating tumour cells or to capture them as a tool to prevent metastasis. The continuous interaction between tissue engineers, biomaterial experts and cancer researchers creates the possibility to biomimic the tumour-environment and provides new opportunities in cancer diagnostics and management. PMID- 26259963 TI - In recurrent primary biliary cirrhosis after liver transplantation, biliary epithelial cells show increased expression of mitochondrial proteins. AB - In biliary epithelial lesions in primary biliary cirrhosis (PBC), mitochondrial proteins associated with deregulated autophagy are abnormally expressed. We examined whether this could be used as a diagnostic marker for end-stage PBC and recurrent PBC after liver transplantation. We examined the expression of the mitochondrial protein pyruvate dehydrogenase complex-E2 component and cytochrome c oxidase, subunit I (CCO), the autophagy-related marker microtubule-associated protein-light chain 3 (LC3), and p62/sequestosome-1 and the senescence markers p16(Ink4a) and p21(WAF1/Cip1) in small bile ducts and bile ductules in explanted livers from patients with PBC (n = 20) in comparison with liver tissue from control patients (n = 21) and post-transplant samples including recurrent PBC and cellular rejection (n = 28). Intense granular expression of mitochondrial proteins was significantly more frequent in small bile ducts in explanted livers with PBC than in control livers (p < 0.05). Post-transplant samples comprised of three groups: group A (positive for mitochondrial proteins, n = 7), group B (positive for either autophagy-related or senescence markers but negative for mitochondrial proteins, n = 7), and group C (all negative, n = 14). All but one case of group A were clinically and histologically diagnosed as recurrent PBC. In contrast, all cases of group B were diagnosed as cellular rejection. This study suggests that the expression of mitochondrial proteins in small bile ducts may be a useful diagnostic marker for end-stage PBC and recurrent PBC after liver transplantation. PMID- 26259964 TI - Target of rapamycin activation predicts lifespan in fruit flies. AB - Aging and age-related diseases are one of the most important health issues that the world will confront during the 21(st) century. Only by understanding the proximal causes will we be able to find treatments to reduce or delay the onset of degenerative diseases associated with aging. Currently, the prevalent paradigm in the field is the accumulation of damage. However, a new theory that proposes an alternative explanation is gaining momentum. The hyperfunction theory proposes that aging is not a consequence of a wear and tear process, but a result of the continuation of developmental programs during adulthood. Here we use Drosophila melanogaster, where evidence supporting both paradigms has been reported, to identify which parameters that have been previously related with lifespan best predict the rate of aging in wild type flies cultured at different temperatures. We find that mitochondrial function and mitochondrial reactive oxygen species (mtROS) generation correlates with metabolic rate, but not with the rate of aging. Importantly, we find that activation of nutrient sensing pathways (i.e. insulin-PI3K/Target of rapamycin (Tor) pathway) correlates with lifespan, but not with metabolic rate. Our results, dissociate metabolic rate and lifespan in wild type flies and instead link nutrient sensing signaling with longevity as predicted by the hyperfunction theory. PMID- 26259965 TI - Management of Functional Constipation in Children: Therapy in Practice. AB - Functional constipation is a common healthcare problem among children worldwide and accounts for high healthcare usage and costs. Functional constipation is a clinical diagnosis; the evaluation primarily consists of a thorough medical history and a complete physical examination. Additional investigations are not necessary in most cases. Treatment consists of non-pharmacological and pharmacological interventions. Non-pharmacological interventions involve education and demystification, toilet training (with a reward system), and a defecation diary. Pharmacological treatment comprises three steps: disimpaction, maintenance treatment, and weaning. The treatment of first choice is oral laxatives, preferably polyethylene glycol. When this is insufficient, other therapeutic agents are available. This review discusses the evaluation and management of functional constipation in the pediatric population and provides a summary of drug treatment options. PMID- 26259967 TI - Long-term ischaemic and bleeding outcomes after primary percutaneous coronary intervention for ST-elevation myocardial infarction in the elderly. AB - BACKGROUND: The population is ageing rapidly and the proportion of patients aged >= 80 years undergoing primary percutaneous coronary intervention (PCI) is rising, but clinical trials have primarily been performed in younger patients. METHODS: Patients undergoing primary PCI between 2003 and 2008 were subdivided into 3 groups: < 60, 60-79, and >= 80 years. Endpoints at 3-year follow-up included all-cause mortality, recurrent myocardial infarction (reMI), stent thrombosis, target lesion revascularisation (TLR), bleeding (BARC bleeding >= 3), stroke, and major adverse cardiovascular events (MACE, a composite of cardiac mortality, reMI, stroke and TLR). RESULTS: 2002 patients with ST-segment elevation myocardial infarction (STEMI) were included, 885 (44.2 %) aged < 60, 921 (46.0 %) 60-79, and 196 (9.7 %) >= 80 years. Comorbidities such as diabetes mellitus, prior stroke, malignant disease, anaemia, and chronic kidney disease were more prevalent in patients >= 80 years. The incidence of both ischaemic and bleeding events strongly increased with age. Age >= 80 years was an independent predictor of mortality (HR 2.56, 95 % CI1.69-3.87, p < 0.001), a borderline non significant predictor of overall bleeding (HR 1.38, 95 %CI 0.95-2.00, p = 0.088), and a significant predictor of non-access site bleeding (HR 2.26, 95 %CI 1.46 3.51, p < 0.001). CONCLUSION: Patients >= 80 years experienced high rates of ischaemic and bleeding complications; especially in this high-risk patient group individualised therapy is needed to optimise clinical outcomes. PMID- 26259968 TI - Cadmium inhibits motility, activities of plasma membrane Ca(2+)-ATPase and axonemal dynein-ATPase of human spermatozoa. AB - Cd(2+) has been associated with decreased sperm motility in individuals exposed to this element, such as smokers. Among other factors, this lowered motility could be the result of inhibition exerted by Cd(2+) on the activity of the sperm ATPases associated with sperm motility. In this study, we evaluated the plasma membrane Ca(2+)-ATPase and the axonemal dynein-ATPase activities as well as sperm motility, in the presence of different free Cd(2+) concentrations in the assay media. It was found that spermatozoa incubated for 5 h in a medium containing 25 nm free Cd(2+) showed a significant inhibition of progressive motility, reaching values even lower at higher Cd(2+) concentrations. In addition, it was found that the activity of the plasma membrane Ca(2+)-ATPase reached maximal inhibition at 50 nm free Cd(2+), with a K50% inhibition of 18.3 nm free Cd(2+). The dynein ATPase activity was maximally inhibited by 25 nm free Cd(2+) in the assay medium, with a K50% inhibition of 11.3 nm Cd(2+). Our results indicate that the decreased activity of the sperm ATPases might have a critical importance in the biochemical mechanisms underlying the decreased sperm motility of individuals exposed to Cd(2+). PMID- 26259966 TI - Impact of Attention-Deficit Hyperactivity Disorder on School Performance: What are the Effects of Medication? AB - Attention-deficit hyperactivity disorder (ADHD) affects an estimated 5-7 % of schoolchildren worldwide. School functioning and academic achievement are frequently impaired by ADHD and represent one of the main reasons children start ADHD medication. Multiple potential causal pathways exist between ADHD and impaired school performance. In this review, we decompose school performance into three components and assess the impact of ADHD and its treatments on academic performance (assessed by grade point average [GPA], time on-task, percentage of work completed as well as percent completed correctly), academic skills (as measured by achievement tests and cognitive measures), and academic enablers (such as study skills, motivation, engagement, classroom behavior and interpersonal skills). Most studies examined only the short-term effects of medication on school performance. In these, ADHD medications have been observed to improve some aspects of school performance, with the largest impact on measures of academic performance such as seatwork productivity and on-task performance. In a subset of children, these benefits may translate into detectable improvements in GPA and achievement testing. However, limited data exists to support whether these changes are sustained over years. Optimizing medication effects requires periodic reassessment of school performance, necessitating a collaborative effort involving patients, parents, school staff and prescribers. Even with systematic reassessment, behavioral-based treatments and additional school-based services may be needed to maximize academic performance for the many youth with ADHD and prominent impairments in school performance. PMID- 26259969 TI - [Erratum to: Mild therapeutic hypothermia]. PMID- 26259970 TI - Effect of strain rate on the toughness of human tibial cortical bone. PMID- 26259971 TI - A revised inventory of Adverse Childhood Experiences. AB - This study examines whether the items from the original Adverse Childhood Experiences (ACE) scale can be improved in their prediction of health outcomes by adding some additional widely recognized childhood adversities. The analyses come from the National Survey of Children's Exposure to Violence 2014, a telephone survey conducted from August 2013 through April 2014 with a nationally representative sample of 1,949 children and adolescents aged 10-17 and their caregivers who were asked about adversities, physical health conditions and mental health symptoms. The addition of measures of peer victimization, peer isolation/rejection, and community violence exposure added significantly to the prediction of mental health symptoms, and the addition of a measure of low socioeconomic status (SES) added significantly to the prediction of physical health problems. A revised version of the ACES scale is proposed. PMID- 26259972 TI - Corporate Social Responsibility programs of Big Food in Australia: a content analysis of industry documents. AB - OBJECTIVE: To examine Corporate Social Responsibility (CSR) tactics by identifying the key characteristics of CSR strategies as described in the corporate documents of selected 'Big Food' companies. METHODS: A mixed methods content analysis was used to analyse the information contained on Australian Big Food company websites. Data sources included company CSR reports and web-based content that related to CSR initiatives employed in Australia. RESULTS: A total of 256 CSR activities were identified across six organisations. Of these, the majority related to the categories of environment (30.5%), responsibility to consumers (25.0%) or community (19.5%). CONCLUSIONS: Big Food companies appear to be using CSR activities to: 1) build brand image through initiatives associated with the environment and responsibility to consumers; 2) target parents and children through community activities; and 3) align themselves with respected organisations and events in an effort to transfer their positive image attributes to their own brands. IMPLICATIONS: Results highlight the type of CSR strategies Big Food companies are employing. These findings serve as a guide to mapping and monitoring CSR as a specific form of marketing. PMID- 26259973 TI - The role of synergic interaction in transition state formation for the aldol reaction on a metal oxide catalyst: a DFT investigation. AB - This contribution highlights an eight-membered ring transition state for the aldol reaction of propanal on O-terminated ZrO2(111) and CeO2(111) surfaces. The relative heights of activation barriers for alpha-H abstraction and nucleophilic addition are controlled by surface acid-base pair strength. We report the first theoretical evidence of an alternative to the Zimmerman-Traxler model. PMID- 26259974 TI - Role of Animal Models in Coronary Stenting. AB - Coronary angioplasty initially employed balloon dilatation only. This technique revolutionized the treatment of coronary artery disease, although outcomes were compromised by acute vessel closure, late constrictive remodeling, and restenosis due to neointimal proliferation. These processes were studied in animal models, which contributed to understanding the biology of endovascular arterial injury. Coronary stents overcome acute recoil, with improvements in the design and metallurgy since then, leading to the development of drug-eluting stents and bioresorbable scaffolds. These devices now undergo computer modeling and benchtop and animal testing before evaluation in clinical trials. Animal models, including rabbit, sheep, dog and pig are available, all with individual benefits and limitations. In smaller mammals, such as mouse and rabbit, the target for stenting is generally the aorta; whereas in larger animals, such as the pig, it is generally the coronary artery. The pig coronary stenting model is a gold standard for evaluating safety; but insights into biomechanical properties, the biology of stenting, and efficacy in controlling neointimal proliferation can also be gained. Intra-coronary imaging modalities such as intravascular ultrasound and optical coherence tomography allow precise serial evaluation in vivo, and recent developments in genetically modified animal models of atherosclerosis provide realistic test beds for future stents and scaffolds. PMID- 26259975 TI - Soft Poly(dimethylsiloxane) Elastomers from Architecture-Driven Entanglement Free Design. AB - Soft, solvent-free poly(dimethylsiloxane) elastomers are fabricated by a one-step process via crosslinking bottlebrush polymers. The bottlebrush architecture prevents the formation of entanglements, resulting in elastomers with precisely controllable low moduli from 1 to 100 kPa, below the lower limit of traditional elastomers; moreover, the solvent-free nature enables their negligible adhesiveness compared to commercially available silicone products of similar stiffness. PMID- 26259976 TI - Comparison of transarterial chemoembolization with radiofrequency ablation for unresectable Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma: a propensity score matching. AB - BACKGROUND AND AIM: Radiofrequency ablation (RFA) is recommended as one of the standard treatments for early hepatocellular carcinoma (HCC). Because of high risk tumor locations unfit for RFA, transarterial chemoembolization (TACE) is served as an alternative option in these settings. To define the role of TACE on early HCC, we retrospectively compared the efficacies of TACE with RFA in patients with unresectable Barcelona Clinic Liver Cancer (BCLC) stage 0/A HCC. MATERIALS AND METHODS: Treatment-naive patients with unresectable BCLC stage 0/A HCC who underwent TACE or RFA were recruited from 2007 to 2011. In all, 208 patients who underwent TACE and 235 patients who underwent RFA were included in the final analysis. Using the propensity model to correct selection bias, 103 patients were selected from each treatment arm. Cumulative overall survival (OS) as the primary end point was compared after adjustment with propensity score matching. RESULTS: In all patients, the OS rate was significantly higher in patients treated with RFA than that in those who received TACE (1-, 3-, and 5 year OS rates, 93.7%, 72.6%, and 58.1% vs 88.1%, 50.3%, and 30.4%, respectively; P < 0.001). However, adjustment with propensity score matching yielded comparable OS between the two groups (P = 0.207). Subgroup analysis showed that RFA provided better OS than TACE in patients with serum gamma-glutamyltranspeptidase < 75 IU/L (P = 0.035). Univariate and subsequent multivariate analyses revealed that Child Pugh class B (hazard ratio = 1.805; 95% confidence interval, 1.805-3.003; P = 0.023) and hepatitis C virus positivity (hazard ratio = 2.478; 95% confidence interval, 1.136-5.404; P = 0.023) were independent predictors of poor prognosis. CONCLUSION: Transarterial chemoembolization is an effective alternative treatment for unresectable BCLC stage 0/A HCC when RFA is not feasible. PMID- 26259977 TI - HGF mediated upregulation of lipocalin 2 regulates MMP9 through nuclear factor kappaB activation. AB - Lipocalin 2 (LCN2) is a member of lipocalin family that binds and transports a small lipophilic ligand, sharing a highly conserved tertiary structure and can be found as a monomer, homodimer, heterodimer with matrix metalloproteinase 9 (MMP9). The high molecule LCN2/MMP9 complex was found in several cancer types. Yet, the mechanisms of regulation between LCN2 with MMP9 in tumorigenesis is unclear. The aims of the present study were to identify the function of LCN2 associated with MMP9 in gastric cancer growth and metastasis. First, we confirmed that the expression level of LCN2 and MMP9 was upregulated by hepatocyte growth factor (HGF). To identify the association pathway of HGF-induced LCN2, the cells were treated with PI3-kinase inhibitor (LY294002), or MEK inhibitor (PD098059), or p38 inhibitor (SB203580) and then analyzed using western blotting. The HGF mediated LCN2 protein level was decreased with LY294002. Also, the HGF-mediated MMP9 was decreased with LY294002. The role for LCN2 with HGF mediated MMP9 was determined by knockdown of LCN2. LCN2-sh RNA cells showed a decreased level of HGF-mediated MMP9. The HGF-mediated LCN2 protein level was decreased with treatment of the NFkappaB inhibitor. We confirmed the role of HGF-mediated LCN2. HGF-mediated cell proliferation and in vitro invasion was decreased in LCN2 knockdown cell. In conclusion, the present study showed that LCN2 upregulated MMP9 through PI3K/AKT/NFkappaB pathway in gastric cancer. LCN2 has a role in cell proliferation and cell invasion in gastric cancer, which may be a possible target for developing gastric cancer therapy. PMID- 26259978 TI - Insulin administered by needle-free jet injection corrects marked hyperglycaemia faster in overweight or obese patients with diabetes. AB - AIMS: To test whether jet injection of insulin resulted in faster correction of marked hyperglycaemia than when insulin is injected by a conventional pen in patients with diabetes. METHODS: Adult, overweight or obese (BMI >=25 and <=40 kg/m(2)) patients with type 1 diabetes (n = 10) or insulin-treated type 2 diabetes (n = 10) were enrolled in a randomized, controlled, crossover study. On two separate occasions, patients were instructed to reduce insulin dose(s) to achieve marked hyperglycaemia (18-23 mmol/l). Subsequently, insulin aspart was administered either by jet injection or by conventional pen, in a dose based on estimated individual insulin sensitivity. Pharmacodynamic and pharmacokinetic profiles were derived from plasma glucose and insulin levels, measured for 6 h after injection. RESULTS: After conventional injection, plasma glucose concentration dropped by >=10 mmol/l after 192.5 +/- 13.6 min. The jet injector advanced this time to 147.9 +/- 14.4 min [difference 44.6 (95% confidence interval 4.3, 84.8); P = 0.03], except in 3 patients who failed to reach this endpoint. The time advantage exceeded 1.5 h in patients with a BMI above the median. Jet injection also reduced the hyperglycaemic burden during the first 2 h (2042 +/- 37.2 vs 2168 +/- 26.1 mmol/min; P = 0.01) and the time to peak insulin levels (40.5 +/- 3.2 vs 76.8 +/- 7.7 min; P < 0.001), but did not increase the risk for hypoglycaemia. CONCLUSIONS: Administration of rapid-acting insulin by jet injection results in faster correction of marked hyperglycaemia in overweight or obese patients with insulin-requiring diabetes. PMID- 26259979 TI - Despite higher body fat content, Ecuadorian subjects with Laron syndrome have less insulin resistance and lower incidence of diabetes than their relatives. AB - In the present pandemics of obesity and insulin resistant diabetes mellitus (DM), the specific contribution of etiological factors such as shifts in nutritional and exercise patterns, genetic and hormonal, is subject of ongoing research. Among the hormonal factors implicated, we selected obesity-driven insulin resistance for further evaluation. It is known that growth hormone (GH) has profound effects on carbohydrate metabolism. In consequence, we compared the effects of the lack of the counter-regulatory effects of GH, in a group of subjects with GH receptor deficiency (GHRD) due to a mutated GH receptor vs. that of their normal relatives. It was found that, despite their obesity, subjects with GHRD, have diminished incidence of diabetes, lower glucose and insulin concentrations, and lower values of indexes indicative of insulin resistance such as HOMA-IR. The GHRD subjects were also capable of appropriately handling glucose or mixed meal loads despite diminished insulin secretion. These observations allow us to suggest that the association of obesity with increased risk for diabetes appears to be dependent on intact growth hormone signaling. PMID- 26259980 TI - Immediate versus conventional loaded single implants in the posterior mandible: a meta-analysis of randomized controlled trials. AB - The purpose of this meta-analysis was to compare implant survival, marginal bone loss, and complications between immediate and conventional loading of single implants installed in the posterior mandible. An extensive electronic search was performed of PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials to identify relevant articles published up to January 2015. After the selection process, five studies met the eligibility criteria and were included. The results of the meta-analysis were expressed in terms of the odds ratio (OR) or standardized mean difference (SMD), with a confidence interval (CI) of 95%. Results were pooled according to heterogeneity using the fixed- or random effects model. There was no statistically significant difference between the two techniques (immediate loading vs. conventional loading) with regard to implant survival (OR 1.71, 95% CI 0.40 to 7.36; P=0.47). There was no statistically significant difference in marginal bone loss (SMD -0.58, 95% CI -1.55 to 0.38; P=0.24). The reported mechanical and biological complications were common to both types of intervention, with the exception of probing depth, which was greater following the immediate loading technique (SMD 0.13, 95% CI -0.19 to 0.44), although this was not statistically significant (P=0.43). PMID- 26259982 TI - Effects of Age, Colony, and Sex on Mercury Concentrations in California Sea Lions. AB - We measured total mercury (THg) concentrations in California sea lions (Zalophus californianus) and examined how concentrations varied with age class, colony, and sex. Because Hg exposure is primarily via diet, we used nitrogen (delta (15)N) and carbon (delta (13)C) stable isotopes to determine if intraspecific differences in THg concentrations could be explained by feeding ecology. Blood and hair were collected from 21 adult females and 57 juveniles from three colonies in central and southern California (San Nicolas, San Miguel, and Ano Nuevo Islands). Total Hg concentrations ranged from 0.01 to 0.31 MUg g(-1) wet weight (ww) in blood and 0.74 to 21.00 MUg g(-1) dry weight (dw) in hair. Adult females had greater mean THg concentrations than juveniles in blood (0.15 vs. 0.03 MUg(-1) ww) and hair (10.10 vs. 3.25 MUg(-1) dw). Age class differences in THg concentrations did not appear to be driven by trophic level or habitat type because there were no differences in delta (15)N or delta (13)C values between adults and juveniles. Total Hg concentrations in adult females were 54 % (blood) and 24 % (hair) greater in females from San Miguel than females from San Nicolas Island, which may have been because sea lions from the two islands foraged in different areas. For juveniles, we detected some differences in THg concentrations with colony and sex, although these were likely due to sampling effects and not ecological differences. Overall, THg concentrations in California sea lions were within the range documented for other marine mammals and were generally below toxicity benchmarks for fish-eating wildlife. PMID- 26259981 TI - FGF 19 and Bile Acids Increase Following Roux-en-Y Gastric Bypass but Not After Medical Management in Patients with Type 2 Diabetes. AB - BACKGROUND: This study aims to quantify changes in fibroblast growth factor 19 (FGF19) and bile acids (BAs) in patients with uncontrolled type 2 diabetes randomized to Roux-en-Y gastric bypass (RYGB) vs intensive medical management (IMM) and matched for similar reduction in HbA1c after 1 year of treatment. METHODS: Blood samples were drawn from patients who underwent a test meal challenge before and 1 year after IMM (n = 15) or RYGB (n = 15). RESULTS: Mean HbA1c decreased from 9.7 to 6.4% after RYGB and from 9.1 to 6.1% in the IMM group. At 12 months, the number of diabetes medications used per subject in the RYGB group (2.5 +/- 0.5) was less than in the IMM group (4.6 +/- 0.3). After RYGB, FGF19 increased in the fasted (93 +/- 15 to 152 +/- 19 pg/ml; P = 0.008) and postprandial states (area under the curve (AUC), 10.8 +/- 1.9 to 23.4 +/- 4.1 pg * h/ml * 10(3); P = 0.006) but remained unchanged following IMM. BAs increased after RYGB (AUC *10(3), 6.63 +/- 1.3 to 15.16 +/- 2.56 MUM * h; P = 0.003) and decreased after IMM (AUC *10(3), 8.22 +/- 1.24 to 5.70 +/- 0.70; P = 0.01). No changes were observed in the ratio of 12alpha-hydroxylated/non-12alpha hyroxylated BAs. Following RYGB, FGF19 AUC correlated with BAs (r = 0.54, P = 0.04) and trended negatively with HbA1c (r = -0.44; P = 0.09); these associations were not observed after IMM. CONCLUSIONS: BA and FGF19 levels increased after RYGB but not after IMM in subjects who achieved similar improvement in glycemic control. Further studies are necessary to determine whether these hormonal changes facilitate improved glucose homeostasis. PMID- 26259983 TI - Vitamin D testing patterns among general practitioners in a major Victorian primary health care service. AB - OBJECTIVE: To examine 25(OH)D testing patterns and frequency among general practitioners in a major community health service. METHOD: A clinical audit of patient records at a community health centre in Melbourne was undertaken. Patients aged 18 years and above were included. Univariate and multivariate logistic regression was used to examine the association between vitamin D testing and socio-demographic characteristics while Poisson regression was used for the frequency of testing. RESULTS: There were 1,217 patients tested for serum 25(OH)D. The community health centre was served by 12 general practitioners and an infectious disease specialist. The odds of vitamin D testing showed a positive, albeit weak, association with age (OR 1.01, 95%CI 1.00-1.02, p<0.05), were higher among females than males (OR 1.42, 95%CI 1.18-1.70, p<0.05) and higher among migrants compared to non-migrants (OR 2.57, 95%CI 2.14-3.09, p<0.05). The frequency of testing was also higher among females than males (IRR 1.17, 95%CI 1.07-1.28, p<0.05) and higher among migrants than non-migrants (IRR 1.19, 95%CI 1.08-1.31, p<0.05). CONCLUSION: Advancing age, being female and being a migrant were associated with an increased likelihood of vitamin D testing. IMPLICATIONS: Development of evidence-based policies and guidelines are needed to manage over-testing of vitamin D in Australia. Studies that include health services from different areas are required to understand vitamin D testing patterns among the general practitioners. PMID- 26259984 TI - Thousands of Ebola survivors experience serious medical complications. PMID- 26259985 TI - Epidemiology of musculoskeletal pain in a pediatric emergency department. AB - The objectives of this study were (1) to determine the percentage of emergency department (ED) visits due to musculoskeletal pain (MSP) by children 3-14 years of age during a period of 1 year; (2) to determine the most frequent presenting complaints; and (3) to characterize their etiology. A cross-sectional study was performed on children aged 3-14(11/12) years attended at the ED of a tertiary hospital due to MSP. The demographic and clinical characteristics of the patients were reviewed 5 days each month for 12 consecutive months. Study days were selected by computer-generated simple random sampling. Out of 4,531 visits to the ED, 826 were due to MSP (18.2 %; 95 % CI 17.1-19.4 %). When compared with children with no skeletal complaints, children with MSP had a similar sex distribution but were older (mean +/- SD 7 +/- 3.5 years vs 9.9 +/- 3.1 years; p < 0.0001). The most common complaints were pain at the wrist (19 %), ankle (19 %) and finger (15 %). The most common etiology was trauma (88.4 %), including contusions (38 %), fractures (21 %) and sprains (18 %). Children with hip (6.7 +/ 3 years; p < 0.0001) and elbow (7.8 +/- 3.5 years; p < 0.0001) complaints were younger than children with pain in other locations, whereas children with wrist pain (10.5 +/- 2.6 years; p < 0.002) and joint sprains (10.7 +/- 2.7 years; p < 0.0001) were older. Fractures were more frequent in boys (64 vs 36 %, p = 0.008; OR 1.6; CI 1.1-2.2). Visits to the ED due to MSP increased with age. Pain at three locations represented 50 % of the presenting complaints. Trauma was the principal etiology, but fractures only represented one-fifth of the total. PMID- 26259987 TI - The Impact of Asking About Interest in Free Nicotine Patches on Smoker's Stated Intent to Change: Real Effect or Artefact of Question Ordering? AB - INTRODUCTION: Stage of change questions are often included on general population surveys to assess the proportion of current smokers intending to quit. The current study reported on a methodological experiment to establish whether participant's self-reported stage of change can be influenced by asking about interest in free nicotine patches immediately prior to asking about intent to change. METHODS: As part of an ongoing random digit dialing survey, a randomized half of participants were asked if they would be interested in receiving nicotine patches to help them quit smoking prior to being asked whether they intended to quit smoking in the next 6 months and 30 days. RESULTS: Participants who were first asked about interest in free nicotine patches were more likely to rate themselves as in preparation for change (asked first = 33%; not asked first = 19%), and less likely to rate themselves as in the precontemplation stage of change (asked first = 34%; not asked first = 47%), compared with participants who were not asked about their interest in free nicotine patches prior to being asked about their stage of change (P < .001). CONCLUSIONS: There are several possible explanations of the results. It is possible that offers of free nicotine patches increases smokers intentions to quit, at least temporarily. Alternatively, smokers being asked about interest in free nicotine patches may expect that the researchers would like to hear about people intending to quit, and respond accordingly. PMID- 26259986 TI - Hookah Tobacco Smoking During the Transition to College: Prevalence of Other Substance Use and Predictors of Initiation. AB - INTRODUCTION: The prevalence of hookah tobacco smoking is increasing, and the transition to college is a vulnerable time for initiation. Hookah use is associated with other forms of substance use, but most research has been cross sectional, thus limiting our understanding of temporal patterns of use. The goals of this longitudinal study were to assess the prevalence of hookah use and initiation, as well as other forms of substance use among hookah users, and identify which forms of substance use predicted hookah initiation during the first 30 days of college. METHODS: Incoming students (N = 936, 50% female) reported on past 30-day substance use prior to the start of the Fall 2011 semester and again 30 days later (n = 817). Substances included hookah, cigarettes, other forms of tobacco, alcohol, marijuana, and other illegal drugs. RESULTS: Current prevalence of hookah use increased from 9.0% before college to 13.1% during the first month of college. At baseline and follow-up, current hookah users were more likely than nonusers to report current use of cigarettes, cigars/little cigars/clove cigarettes, smokeless tobacco, marijuana, and alcohol. Among pre-college hookah never users, 13.8% initiated hookah use in the first month of college. Alcohol (adjusted odds ratio [AOR] 1.11, 95% confidence interval [CI] 1.05, 1.17) and marijuana (AOR 1.30, 95% CI 1.03, 1.65) were the only substances predictive of hookah initiation. CONCLUSIONS: Findings indicate that hookah prevention and intervention is needed during the transition to college, and interventions may need to address comorbid alcohol, marijuana, and hookah use. IMPLICATIONS: To our knowledge this is the first longitudinal study examining predictors of hookah initiation among male and female incoming first year college students. While hookah users were more likely than nonusers to use all other substances before and during the first month of college, pre-college marijuana and alcohol use were the only two predictors of hookah initiation during the first 30 days of college. Collectively, these findings provide additional support for the need for efficacious hookah prevention and intervention programs. The transition to college appears to be an ideal time to deliver prevention programs given the increased prevalence of hookah use during the first 30 days of college. In addition to prevention, former users may benefit from targeted relapse prevention as one-fifth of former hookah smokers resumed use during the first 30 days of college. PMID- 26259988 TI - Menthol Content in US Marketed Cigarettes. AB - INTRODUCTION: In 2011 menthol cigarettes accounted for 32 percent of the market in the United States, but there are few literature reports that provide measured menthol data for commercial cigarettes. To assess current menthol application levels in the US cigarette market, menthol levels in cigarettes labeled or not labeled to contain menthol was determined for a variety of contemporary domestic cigarette products. METHOD: We measured the menthol content of 45 whole cigarettes using a validated gas chromatography/mass spectrometry method. RESULTS: In 23 cigarette brands labeled as menthol products, the menthol levels of the whole cigarette ranged from 2.9 to 19.6mg/cigarette, with three products having higher levels of menthol relative to the other menthol products. The menthol levels for 22 cigarette products not labeled to contain menthol ranged from 0.002 to 0.07mg/cigarette. The type of packaging (soft vs. hard pack) for a given cigarette product does not appear to affect menthol levels based on the current limited data. CONCLUSIONS: Menthol levels in cigarette products labeled as containing menthol are approximately 50- to 5000-fold higher than those in cigarette products not labeled as containing menthol. In general, menthol content appears to occur within discrete ranges for both mentholated and nonmentholated cigarettes. IMPLICATIONS: This study shows that menthol may be present in non mentholated cigarettes and adds to the understanding of how menthol may be used in cigarette products. It is the first systematic study from the same laboratory which will readily enable comparison among menthol and non-menthol cigarettes. PMID- 26259989 TI - Ustekinumab in adolescent patients age 12 to 17 years with moderate-to-severe plaque psoriasis: results of the randomized phase 3 CADMUS study. AB - BACKGROUND: Safe and effective therapies are needed for pediatric patients with psoriasis. OBJECTIVE: The purpose of this study was to evaluate ustekinumab in patients age 12 to 17 years who had moderate-to-severe psoriasis. METHODS: Patients (n = 110) were randomly assigned to ustekinumab standard dosing (SD; 0.75 mg/kg [<=60 kg], 45 mg [>60-<=100 kg], and 90 mg [>100 kg]) or half-standard dosing (HSD; 0.375 mg/kg [<=60 kg], 22.5 mg [>60-<=100 kg], and 45 mg [>100 kg]) at weeks 0 and 4 and every 12 weeks or placebo at weeks 0 and 4 with crossover to ustekinumab SD or HSD at week 12. Clinical assessments included the proportion of patients achieving a Physician's Global Assessment of cleared/minimal (PGA 0/1), at least 75% improvement in Psoriasis Area and Severity Index (PASI 75), and at least 90% in PASI (PASI 90). Adverse events (AEs) were monitored through week 60. RESULTS: At week 12, 67.6% and 69.4% of patients receiving ustekinumab HSD and SD, respectively, achieved PGA 0/1 versus 5.4% for placebo (P < .001). Significantly greater proportions receiving ustekinumab achieved PASI 75 (HSD, 78.4%; SD, 80.6%; placebo, 10.8%) or PASI 90 (HSD, 54.1%; SD, 61.1%; placebo, 5.4%) at week 12 (P < .001). Through week 12, 56.8% of placebo patients, 51.4% of HSD patients, and 44.4% of SD patients reported at least one AE; through week 60, 81.8% reported AEs. LIMITATIONS: The study was small relative to adult trials. CONCLUSIONS: In this patient population (12-17 years), the standard ustekinumab dose provided response comparable to that in adults with no unexpected AEs through 1 year. PMID- 26259991 TI - Bladder Neck Muscle Degeneration in Patients with Prostatic Hyperplasia. AB - PURPOSE: To improve understanding of the variations of bladder neck musculature we investigated histological changes of the bladder neck associated with prostatic hyperplasia in adult male cadavers. MATERIALS AND METHODS: We examined histological sections from 24 donated male cadavers with a mean age of 74 years. Sections were subjected to Azan and immunohistochemical staining using desmin and S-100 antibodies. The collagen content per cross-sectional area was calculated and statistically compared. RESULTS: The existence of 3 muscle layers (submucosal longitudinal muscles, circular bladder neck muscles and external longitudinal muscles) was confirmed at the anterior and posterior regions of the bladder neck. Increased prostate volume significantly correlated with an increase in collagen fibers and thinning of muscle bundles in the anterior bladder neck. An increase in prostate volume and increasing age significantly correlated with degeneration of the posterior bladder neck muscles. As prostatic hyperplasia advanced the bladder neck muscles were progressively affected by fibrosis with the circular muscle fibers becoming thin and fragmented. In addition the severity of fibrosis associated with prostatic hyperplasia showed interindividual variation. We also devised a schematic classification of bladder neck morphology in men. CONCLUSIONS: Degeneration of muscle bundles in the bladder neck of men with prostatic hyperplasia was confirmed. It was found that the bundles became thinner along with an increase in collagenous tissue. Our schematic classification of bladder neck morphology in men may be useful for further investigations. PMID- 26259990 TI - 100% Complete response rate in patients with cutaneous metastatic melanoma treated with intralesional interleukin (IL)-2, imiquimod, and topical retinoid combination therapy: results of a case series. AB - BACKGROUND: Patients with cutaneous melanoma metastases have experienced excellent responses to intralesional interleukin (IL)-2. This has led to its recent inclusion into the US National Comprehensive Cancer Network guidelines for management of cutaneous melanoma metastases. Despite this, intralesional IL-2 has not been highlighted in the US literature nor have US physicians adopted it. OBJECTIVE: We sought to evaluate the effectiveness of intralesional IL-2 combined with topical imiquimod and retinoid for treatment of cutaneous metastatic melanoma. METHODS: A retrospective case series of 11 patients with cutaneous metastatic melanoma were treated with intralesional IL-2 combined with topical imiquimod and retinoid. RESULTS: A 100% complete local response rate with long term follow-up (average of 24 months) was seen in all 11 patients treated with this proposed regimen. Biopsy specimens of treated sites confirmed absence of malignant cells. The most common treatment-related adverse event was rigors. LIMITATIONS: Small number of patients, retrospective review of charts, and lack of a comparison group were limitations. CONCLUSION: Intralesional IL-2 administered concomitantly with topical imiquimod and a retinoid cream is a promising therapeutic option for managing cutaneous melanoma metastases. The regimen was well tolerated and should be considered as a reasonable alternative to surgical excision. PMID- 26259992 TI - One Question, Multiple Answers: Biochemical and Biophysical Screening Methods Retrieve Deviating Fragment Hit Lists. AB - Fragment-based lead discovery is gaining momentum in drug development. Typically, a hierarchical cascade of several screening techniques is consulted to identify fragment hits which are then analyzed by crystallography. Because crystal structures with bound fragments are essential for the subsequent hit-to-lead-to drug optimization, the screening process should distinguish reliably between binders and non-binders. We therefore investigated whether different screening methods would reveal similar collections of putative binders. First we used a biochemical assay to identify fragments that bind to endothiapepsin, a surrogate for disease-relevant aspartic proteases. In a comprehensive screening approach, we then evaluated our 361-entry library by using a reporter-displacement assay, saturation-transfer difference NMR, native mass spectrometry, thermophoresis, and a thermal shift assay. While the combined results of these screening methods retrieve 10 of the 11 crystal structures originally predicted by the biochemical assay, the mutual overlap of individual hit lists is surprisingly low, highlighting that each technique operates on different biophysical principles and conditions. PMID- 26259993 TI - Lobectomy versus stereotactic body radiotherapy for stage I non-small cell lung cancer: Post hoc analysis dressed up as level-1 evidence? PMID- 26259994 TI - Adding radiation to induction chemotherapy does not improve survival of patients with operable clinical N2 non-small cell lung cancer. AB - OBJECTIVE: Radiotherapy is commonly used in induction regimens for patients with non-small cell lung cancer with operable mediastinal nodal disease, although evidence has not shown a benefit over induction chemotherapy alone. We compared outcomes between induction chemotherapy and induction chemoradiation using the National Cancer Data Base. METHODS: Induction radiation use and survival of patients who underwent lobectomy or pneumonectomy after induction chemotherapy for clinical T1-3N2M0 non-small cell lung cancer in the National Cancer Data Base from 2003 to 2006 were assessed using logistic regression, general linear regression, Kaplan-Meier, and Cox proportional hazard analysis. RESULTS: Of 1362 patients who met study criteria, 834 (61%) underwent induction chemoradiation and 528 (39%) underwent induction chemotherapy. Lobectomy was performed in 82% of patients (n = 1111), and pneumonectomy was performed in 18% of patients (n = 251). Pneumonectomy was performed more often after induction chemoradiation than after induction chemotherapy (20% vs 16%, P = .04). Downstaging from N2 to N0/N1 was more common with induction chemoradiation compared with induction chemotherapy (58% vs 46%, P < .01), but 5-year survival of patients receiving induction chemoradiation and patients receiving induction chemotherapy was similar in unadjusted analysis (41% vs 41%, P = .41). In multivariable analysis, the addition of radiation to induction chemotherapy also was not associated with a survival benefit (hazard ratio, 1.03; 95% confidence interval, 0.89-1.18; P = .73). CONCLUSIONS: Induction chemoradiation is used in the majority of patients with non-small cell lung cancer with N2 disease who undergo induction therapy before surgical resection, but it is not associated with improved survival compared with induction chemotherapy. PMID- 26259996 TI - Predictive Bayesian inference and dynamic treatment regimes. AB - While optimal dynamic treatment regimes (DTRs) can be estimated without specification of a predictive model, a model-based approach, combined with dynamic programming and Monte Carlo integration, enables direct probabilistic comparisons between the outcomes under the optimal DTR and alternative (dynamic or static) treatment regimes. The Bayesian predictive approach also circumvents problems related to frequentist estimators under the nonregular estimation problem. However, the model-based approach is susceptible to misspecification, in particular of the "null-paradox" type, which is due to the model parameters not having a direct causal interpretation in the presence of latent individual-level characteristics. Because it is reasonable to insist on correct inferences under the null of no difference between the alternative treatment regimes, we discuss how to achieve this through a "null-robust" reparametrization of the problem in a longitudinal setting. Since we argue that causal inference can be entirely understood as posterior predictive inference in a hypothetical population without covariate imbalances, we also discuss how controlling for confounding through inverse probability of treatment weighting can be justified and incorporated in the Bayesian setting. PMID- 26259997 TI - Re: Guido Barbagli, Massimo Lazzeri. Clinical Experience with Urethral Reconstruction Using Tissue-engineered Oral Mucosa: A Quiet Revolution. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2015.05.043. PMID- 26259998 TI - Prevalence of Female Urinary Incontinence in the General Population According to Different Definitions and Study Designs. AB - BACKGROUND: Estimates of the prevalence of female urinary incontinence (UI) vary widely. OBJECTIVE: To estimate UI prevalence among women in France using data from five national surveys and analyse prevalence differences among the surveys according to their design (representative sample or not, survey focused on UI or not) and UI definition (based on symptoms or disease perception). DESIGN, SETTING, AND PARTICIPANTS: Data came from two representative telephone surveys, Fecond (5017 women aged 15-49 yr) and Barometer (3089 women aged 40-85 yr), general and urinary postal surveys of the GAZEL cohort (3098 women aged 54-69 yr), and the web-based NutriNet survey (85,037 women aged 18-87 yr). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Definitions of UI based on the International Conference on Incontinence Questionnaire UI short form (ICIQ-UI-SF) and on a list of health problems were considered. We compared age-adjusted prevalence rates among studies via logistic regression and generalised linear models. RESULTS AND LIMITATIONS: Overall, 13% of the women in Fecond, 24% in Barometer, 15% in the GAZEL general survey, 39% in the GAZEL urinary survey, and 1.5% in the NutriNet survey reported any UI. Prevalence rates in representative samples with the same UI definition (ICIQ-UI-SF) were concordant. UI prevalence in the representative samples was 17%. The estimated number of women in France with UI was 5.35 million (95% confidence interval [CI] 5.34-5.36 million) for any UI and 1.54 million (95% CI 1.53-1.55 million) for daily UI. For the GAZEL sample, UI prevalence was lower but UI severity was greater for responses to a questionnaire with the list-based UI definition rather than to a questionnaire with the ICIQ-UI-SF-based definition. In all surveys, information about UI was self-reported and was not validated by objective measurements. CONCLUSIONS: UI definitions and sampling strategies influence estimates of UI prevalence among women. Precise estimates of UI prevalence should be based on non-UI-focused surveys among representative samples and using a validated standardised symptom based questionnaire. PATIENT SUMMARY: We looked at estimates of urinary incontinence (UI) prevalence in studies with different designs and different UI definitions in a large population of French women. We found that estimates varied with the definition and the design. We conclude that the most precise estimates of UI prevalence are obtained in studies of representative populations that are not focused on UI and use a validated international standard questionnaire with sufficient details to allow grading of UI severity. Most women reported rare urine leakages involving small amounts of urine with little impact on their quality of life. PMID- 26259999 TI - Application and Integration of Live Streaming from Leading Robotic Centres Can Enhance Surgical Education. AB - Internet-based video-streaming enables us to share surgical knowledge and to study leading surgeons while they operate in their home institutions, and is widely accessible to trainees. Planned developments include enriched learning experiences with improved user friendliness, interactivity, and real-time feedback. PMID- 26260000 TI - Finding Minimal Extraprostatic Disease: Who Cares? PMID- 26260001 TI - Reply from Authors re: Tahlita C.M. Zuiverloon, Ellen C. Zwarthoff. Predicting Response to Intravesical Bacillus Calmette-Guerin Immunotherapy: Are We Moving Forward? Eur Urol 2016;69:201-2: The Goal: Individualized Bacillus Calmette Guerin Therapy. PMID- 26260002 TI - Reply to Nadir I. Osman, Christopher R. Chapple, Sheila MacNeil's Letter to the Editor re: Guido Barbagli, Massimo Lazzeri. Clinical Experience with Urethral Reconstruction Using Tissue-engineered Oral Mucosa: A Quiet Revolution. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2015.05.043. PMID- 26260003 TI - Structural measures to track the evolution of SNOMED CT hierarchies. AB - The Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) is an extensive reference terminology with an attendant amount of complexity. It has been updated continuously and revisions have been released semi-annually to meet users' needs and to reflect the results of quality assurance (QA) activities. Two measures based on structural features are proposed to track the effects of both natural terminology growth and QA activities based on aspects of the complexity of SNOMED CT. These two measures, called the structural density measure and accumulated structural measure, are derived based on two abstraction networks, the area taxonomy and the partial-area taxonomy. The measures derive from attribute relationship distributions and various concept groupings that are associated with the abstraction networks. They are used to track the trends in the complexity of structures as SNOMED CT changes over time. The measures were calculated for consecutive releases of five SNOMED CT hierarchies, including the Specimen hierarchy. The structural density measure shows that natural growth tends to move a hierarchy's structure toward a more complex state, whereas the accumulated structural measure shows that QA processes tend to move a hierarchy's structure toward a less complex state. It is also observed that both the structural density and accumulated structural measures are useful tools to track the evolution of an entire SNOMED CT hierarchy and reveal internal concept migration within it. PMID- 26260004 TI - A broad-spectrum integrative design for cancer prevention and therapy: The challenge ahead. AB - Despite exciting advances in targeted therapies, high drug costs, marginal therapeutic benefits and notable toxicities are concerning aspects of today's cancer treatments. This special issue of Seminars in Cancer Biology proposes a broad-spectrum, integrative therapeutic model to complement targeted therapies. Based on extensive reviews of the cancer hallmarks, this model selects multiple high-priority targets for each hallmark, to be approached with combinations of low-toxicity, low-cost therapeutics, including phytochemicals, adapted to the well-known complexity and heterogeneity of malignancy. A global consortium of researchers has been assembled to advance this concept, which is especially relevant in an era of rapidly expanding capacity for genomic tumor analyses, alongside alarming growth in cancer morbidity and mortality in low- and middle income nations. PMID- 26260005 TI - Microbial production of lactic acid: the latest development. AB - Lactic acid is an important platform chemical for producing polylactic acid (PLA) and other value-added products. It is naturally produced by a wide spectrum of microbes including bacteria, yeast and filamentous fungi. In general, bacteria ferment C5 and C6 sugars to lactic acid by either homo- or hetero-fermentative mode. Xylose isomerase, phosphoketolase, transaldolase, l- and d-lactate dehydrogenases are the key enzymes that affect the ways of lactic acid production. Metabolic engineering of microbial strains are usually needed to produce lactic acid from unconventional carbon sources. Production of d-LA has attracted much attention due to the demand for producing thermostable PLA, but large scale production of d-LA has not yet been commercialized. Thermophilic Bacillus coagulans strains are able to produce l-lactic acid from lignocellulose sugars homo-fermentatively under non-sterilized conditions, but the lack of genetic tools for metabolically engineering them severely affects their development for industrial applications. Pre-treatment of agriculture biomass to obtain fermentable sugars is a pre-requisite for utilization of the huge amounts of agricultural biomass to produce lactic acid. The major challenge is to obtain quality sugars of high concentrations in a cost effective-way. To avoid or minimize the use of neutralizing agents during fermentation, genetically engineering the strains to make them resist acidic environment and produce lactic acid at low pH would be very helpful for reducing the production cost of lactic acid. PMID- 26260006 TI - Respiratory neuromodulation in patients with neurological pathologies: for whom and how? AB - Implanted phrenic nerve stimulation is a technique restoring spontaneous breathing in patients with respiratory control failure, leading to being dependent on mechanical ventilation. This is the case for quadriplegic patients with a high spinal cord injury level and for patients with congenital central hypoventilation syndrome. The electrophysiological diaphragm explorations permits better patient selection, confirming on the one hand a definite issue with central respiratory command and on the other hand the integrity of diaphragmatic phrenic nerves. Today there are two different phrenic stimulation techniques: the quadripolar intrathoracic stimulation and the bipolar intradiaphragmatic stimulation. Both techniques allow patients to be weaned off their mechanical ventilator, improving dramatically their quality of life. In fact, one of the systems (phrenic intradiaphragmatic stimulation) was granted social security reimbursement in 2009, and now both are reimbursed. In the future, phrenic intradiaphragmatic stimulation may find its place in the intensive care unit, for patients needing it temporarily, for example, after certain surgeries with respiratory complications as well as diaphragmatic atrophies induced by prolonged mechanical ventilation. PMID- 26260007 TI - Balance characteristics in patients with major depression after a two-month walking exercise program: A pilot study. AB - Recent studies have demonstrated impaired balance performance in patients with major depressive disorder (MDD) in comparison to healthy controls (HC), which is likely to be related to deficits in integration of visual and proprioceptive inputs necessary for efficient postural control. In parallel, considerable literature supports the positive effects of a walking program on depressive symptoms. Thus this study aimed to determine the effects of a two-month walking program on implicit postural control strategies in MDD. Compared with twelve age- and body mass index-matched non-psychiatric HC (mean age 50.41 +/- 6.93 years; five women), nine MDD (mean age 51.88 +/- 10.01 years; five women) performed two sessions of standing postural control assessment, separated by eight weeks of the walking program, while the HC were only assessed at t0. The walking program included one-hour supervised walking sessions, three times a week over a two month period. Postural performance was assessed by various center of pressure (COP) parameters, in particular those that bound the COP velocity of postural sway. The primary findings were that MDD patients exhibited positive physical activity-related changes in postural performance, with a decrease in body sway in the most difficult condition (with a foam surface). The real impact of the walking program on COP velocity-based variables suggests that MDD patients improved their ability to make more efficient postural corrections, which is useful for daily activities and autonomy. A balance assessment in the clinical screening routine might be used as a new index of the effectiveness of walking programs recommended for people with depression. TRIAL REGISTRATION: This study is registered at http://clinicaltrials.gov/: NCT01995422. PMID- 26260008 TI - Differences in trunk control between early and late pregnancy during gait. AB - The aim of this study was to compare gait characteristics, including the functional ability of the trunk, between women before and during the third trimester of pregnancy. Gait measurements were performed on 27 pregnant women, who were divided into two groups using the threshold of 28 gestational weeks. The subjects were instructed to walk at their preferred speed. In addition to stride time coefficient of variation, root mean square (RMS) and autocorrelation coefficient, coefficient of attenuation (CoA) of acceleration was computed as an index to assess the functional ability of the trunk. Differences of gait characteristics between the groups were determined by the Mann-Whitney U test. Gait characteristics that showed a significant difference between the groups were further analyzed with adjustment by age, height, weight and gait velocity by using multiple regression analysis. Women during the third trimester of pregnancy showed significantly smaller RMS in the anteroposterior direction at the lower trunk than those before the third trimester of pregnancy, even after adjusting for age, height, weight and gait velocity [beta=0.47; 95% confidence interval (CI) 0.07-0.25]. CoA in the anteroposterior direction was also significantly lower in women during the third trimester of pregnancy than in those before the third trimester of pregnancy after adjustment by age, height, weight and gait velocity (beta=0.44; 95% CI 0.39-18.52). The present cross-sectional study suggests the possibility that the functional ability of the trunk during gait declines in late pregnancy. PMID- 26260009 TI - Long-term outcomes after multilevel surgery including rectus femoris, hamstring and gastrocnemius procedures in children with cerebral palsy. AB - BACKGROUND/AIMS: Multilevel surgical intervention is a common approach for the correction of gait abnormalities in children with cerebral palsy (CP). The short term outcomes for the combination of rectus femoris transfer, hamstring lengthening and gastrocnemius lengthening have been well documented using three dimensional motion analysis. However, the impact of time, growth, and puberty on these short-term outcomes of this combination of procedures is not well understood. The purpose of this study was to evaluate the long-term outcomes of these procedures on gait in patients with CP. METHODS: Twenty-two patients underwent rectus femoris transfers, medial hamstring lengthenings and gastrocnemius lengthenings in combination with a selection of other soft tissue and/or bony procedures of the lower limb. All patients had a pre-operative motion analysis and post-operative analysis one and 11 years following surgery. RESULTS: Significant changes in both clinical and gait variables from pre to 1 year post surgery confirmed the short-term gait benefits of this combination of surgical procedures. Long-term follow-up data indicated that the passive range of motion gains noted 1 year after surgery were lost at the knee and ankle. However, the improvements in ankle dorsiflexion and knee extension at initial contact were maintained over 11 years. As well, peak ankle dorsiflexion in stance was maintained and peak ankle plantar flexor moments and powers did not show declines long-term. Peak knee flexion showed a decline over the long-term, however, the timing of peak knee flexion in swing was maintained. CONCLUSION: When compared to declines in gait kinematics in persons with CP without surgery, these results demonstrate the possible long-term benefits of surgical intervention. PMID- 26260010 TI - Obese older adults suffer foot pain and foot-related functional limitation. AB - There is evidence to suggest being overweight or obese places adults at greater risk of developing foot complications such as osteoarthritis, tendonitis and plantar fasciitis. However, no research has comprehensively examined the effects of overweight or obesity on the feet of individuals older than 60 years of age. Therefore we investigated whether foot pain, foot structure, and/or foot function is affected by obesity in older adults. Three hundred and twelve Australian men and women, aged over 60 years, completed validated questionnaires to establish the presence of foot pain and health related quality of life. Foot structure (anthropometrics and soft tissue thickness) and foot function (ankle dorsiflexion strength and flexibility, toe flexor strength, plantar pressures and spatiotemporal gait parameters) were also measured. Obese participants (BMI >30) were compared to those who were overweight (BMI=25-30) and not overweight (BMI <25). Obese participants were found to have a significantly higher prevalence of foot pain and scored significantly lower on the SF-36. Obesity was also associated with foot-related functional limitation whereby ankle dorsiflexion strength, hallux and lesser toe strength, stride/step length and walking speed were significantly reduced in obese participants compared to their leaner counterparts. Therefore, disabling foot pain and altered foot structure and foot function are consequences of obesity for older adults, and impact upon their quality of life. Interventions designed to reduce excess fat mass may relieve loading of the foot structures and, in turn, improve foot pain and quality of life for older obese individuals. PMID- 26260011 TI - Interaction of Virus-Like Particles with Vesicles Containing Glycolipids: Kinetics of Detachment. AB - Many viruses interact with their host cells via glycosphingolipids (GSLs) and/or glycoproteins present on the outer cell membrane. This highly specific interaction includes virion attachment and detachment. The residence time determined by the detachment is particularly interesting, since it is directly related to internalization and infection as well as to virion egress and spreading. In an attempt to deepen the understanding of virion detachment kinetics, we have used total internal reflection fluorescence (TIRF) microscopy to probe the interaction between individual fluorescently labeled GSL-containing lipid vesicles and surface-bound virus-like particles (VLPs) of a norovirus genotype II.4 strain. The distribution of the VLP-vesicle residence time was investigated for seven naturally occurring GSLs, all of which are candidates for the not yet identified receptor(s) mediating norovirus entry into host cells. As expected for interactions involving multiple GSL binding sites at a viral capsid, the detachment kinetics displayed features typical for a broad activation-energy distribution for all GSLs. Detailed inspection of these distributions revealed significant differences among the different GSLs. The results are discussed in terms of strength of the interaction, vesicle size, as well as spatial distribution and clustering of GSLs in the vesicle membrane. PMID- 26260013 TI - Pitfalls of the MTT assay: Direct and off-target effects of inhibitors can result in over/underestimation of cell viability. AB - The MTT assay (to a less degree MTS, XTT or WST) is a widely exploited approach for measuring cell viability/drug cytotoxicity. MTT reduction occurs throughout a cell and can be significantly affected by a number of factors, including metabolic and energy perturbations, changes in the activity of oxidoreductases, endo-/exocytosis and intracellular trafficking. Over/underestimation of cell viability by the MTT assay may be due to both adaptive metabolic and mitochondrial reprogramming of cells subjected to drug treatment-mediated stress and inhibitor off-target effects. Previously, imatinib, rottlerin, ursolic acid, verapamil, resveratrol, genistein nanoparticles and some polypeptides were shown to interfere with MTT reduction rate resulting in inconsistent results between the MTT assay and alternative assays. Here, to test the under/overestimation of viability by the MTT assay, we compared results derived from the MTT assay with the trypan blue exclusion assay after treatment of glioblastoma U251, T98G and C6 cells with three widely used inhibitors with the known direct and side effects on energy and metabolic homeostasis - temozolomide (TMZ), a DNA-methylating agent, temsirolimus (TEM), an inhibitor of mTOR kinase, and U0126, an inhibitor of MEK1/2 kinases. Inhibitors were applied shortly as in IC50 evaluating studies or long as in studies focusing on drug resistance acquisition. We showed that over/underestimation of cell viability by the MTT assay and its significance depends on a cell line, a time point of viability measurement and other experimental parameters. Furthermore, we provided a comprehensive survey of factors that should be accounted in the MTT assay. To avoid result misinterpretation, supplementation of the tetrazolium salt-based assays with other non-metabolic assays is recommended. PMID- 26260012 TI - Dominant negative Ras attenuates pathological ventricular remodeling in pressure overload cardiac hypertrophy. AB - The importance of the oncogene Ras in cardiac hypertrophy is well appreciated. The hypertrophic effects of the constitutively active mutant Ras-Val12 are revealed by clinical syndromes due to the Ras mutations and experimental studies. We examined the possible anti-hypertrophic effect of Ras inhibition in vitro using rat neonatal cardiomyocytes (NRCM) and in vivo in the setting of pressure overload left ventricular (LV) hypertrophy (POH) in rats. Ras functions were modulated via adenovirus directed gene transfer of active mutant Ras-Val12 or dominant negative mutant N17-DN-Ras (DN-Ras). Ras-Val12 expression in vitro activates NFAT resulting in pro-hypertrophic and cardio-toxic effects on NRCM beating and Z-line organization. In contrast, the DN-Ras was antihypertrophic on NRCM, inhibited NFAT and exerted cardio-protective effects attested by preserved NRCM beating and Z line structure. Additional experiments with silencing H-Ras gene strategy corroborated the antihypertrophic effects of siRNA-H-Ras on NRCM. In vivo, with the POH model, both Ras mutants were associated with similar hypertrophy two weeks after simultaneous induction of POH and Ras-mutant gene transfer. However, LV diameters were higher and LV fractional shortening lower in the Ras-Val12 group compared to control and DN-Ras. Moreover, DN-Ras reduced the cross-sectional area of cardiomyocytes in vivo, and decreased the expression of markers of pathologic cardiac hypertrophy. In isolated adult cardiomyocytes after 2 weeks of POH and Ras-mutant gene transfer, DN-Ras improved sarcomere shortening and calcium transients compared to Ras-Val12. Overall, DN-Ras promotes a more physiological form of hypertrophy, suggesting an interesting therapeutic target for pathological cardiac hypertrophy. PMID- 26260014 TI - Identification of genes associated with male sterility in a mutant of white birch (Betula platyphylla Suk.). AB - White birch (Betula platyphylla Suk.) is a monoecious tree species with unisexual flowers. In this study, we used a spontaneous mutant genotype that produced normal-like male (NLM) inflorescences and mutant male (MM) inflorescences at different locations within the tree to investigate the genes necessary for pollen development. A cDNA-amplified fragment length polymorphism (cDNA-AFLP) analysis was used to identify genes differentially expressed between the two types of inflorescences. Of approximately 5000 transcript-derived fragments (TDFs) obtained, 323 were significantly differentially expressed, of which 141 were successfully sequenced. BLAST analyses revealed 51.8% of the sequenced TDFs showed significant homology with proteins of known or predicted functions, 10.6% showed significant homology with putative proteins without any known or predicted function, and the remaining 37.6% had no hits in the NCBI database. Further, in a functional categorization based on the BLAST analyses, the protein fate, metabolism, energy categories had in order the highest percentages of the proteins. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the known TDFs were mainly involved in metabolic (28.4%), signal transduction (23.5%) and folding, sorting and degradation (13.6%) pathways. Ten genes from the NLM and MM development stages in the mutant were analyzed by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR). The information generated in this study can provide some useful clues to help understand male sterility in B. platyphylla. PMID- 26260015 TI - Identification of hub glycogenes and their nsSNP analysis from mouse RNA-Seq data. AB - Glycogenes regulate a large number of biological processes such as cancer and development. In this work, we created an interaction network of 923 glycogenes to detect potential hubs from different mouse tissues using RNA-Seq data. DAVID functional cluster analysis revealed enrichment of immune response, glycoprotein and cholesterol metabolic processes. We also explored nsSNPs that may modify the expression and function of identified hubs using computational methods. We observe that the number of nsSNPs predicted by any two methods to affect protein function is 4, 7 and 2 for FLT1, NID2 and TNFRSF1B. Residues in the native and mutant proteins were analyzed for solvent accessibility and secondary structure change. Analysis of hubs can help in determining their degree of conservation and understanding their functions in biological processes. The nsSNPs proposed in this work may be further targeted through experimental methods for understanding structural and functional relationships of hub mutants. PMID- 26260016 TI - First proteome study of sporadic flowering in bamboo species (Bambusa vulgaris and Dendrocalamus manipureanus) reveal the boom is associated with stress and mobile genetic elements. AB - Bamboo species are the fastest-growing plants having a long vegetative cycle. Abrupt switching from the vegetative phase to the reproductive phase via sporadic flowering boom, occasionally leads to death of bamboo clumps, and threatens the existence of many bamboo species. To apprehend the molecular mechanism driving sporadic flowering, proteome changes in the initial and advanced floral buds of two edible bamboo species (Bambusa vulgaris and Dendrocalamus manipureanus) was dissected by two-dimensional gel electrophoresis (2-DE). A total of 39 differentially expressed peptide spots were identified by matrix-assisted laser desorption ionization time-of-flight/time-of-flight mass spectrometry (MALDI-TOF TOF/MS). In both B. vulgaris and D. manipureanus, identified proteins were categorized as transposon-related, defence and stress-related, cell cycle related, metabolism related, signal transduction related, and some lacked known putative domains. Proteins such as SEPALLATA3, ubiquitin, histone 3, thaumatin like protein, putative tethering factor, SF-assemblin, polyubiquitin, mitochondrial carrier-like protein and RPT2-like protein were significantly expressed. Differences in D. manipureanus and B. vulgaris suggested that bamboo species have diverse 'drivers' or 'passengers' genes that govern natural sporadic flowering boom. This first floral proteomics analysis of bamboos revealed that sporadic boom is a highly energetic process, associated with stress elements, mobile genetic elements and signal transduction cross-talk elements. PMID- 26260017 TI - Identification, molecular characterization and gene expression analysis of sox1a and sox1b genes in Japanese flounder, Paralichthys olivaceus. AB - The transcription factor, Sox1 has been implicated in neural determination and differentiation as well as in the maintenance of neural progenitor cell status in mammals. However, the molecular cloning and expression of sox1 gene in marine fish have not been reported yet. In this study, we first cloned and characterized the full-length cDNAs and the partial 5'-flanking regions of Paralichthys olivaceus sox1a (Posox1a) and sox1b (Posox1b). Phylogenetic, gene structure, and chromosome synteny analyses revealed that Posox1a and Posox1b were co-orthologs and homologous to mammalian Sox1. The promoter regions of Posox1a and Posox1b were also analyzed and several potential transcription factor (TF) binding sites were identified which might modulate gene expression. Quantitative real-time RT PCR (qRT-PCR) results showed that Posox1a and Posox1b were consistently expressed during embryogenesis, with the highest level at the neurula stage. Tissue distribution analyses revealed that Posox1a and Posox1b were abundant in the adult brain. Moreover, Posox1a had a faster evolution rate and much higher expression levels than Posox1b. These results provide a foundation for further surveying the function of PoSox1 genes during Japanese flounder development and neurogenesis. PMID- 26260018 TI - Ablative CO2 fractional resurfacing in treatment of thermal burn scars: an open label controlled clinical and histopathological study. AB - INTRODUCTION: Burn scars can cause permanent disfiguring problems with limited treatments available. OBJECTIVES: To assess and correlate the clinical and histopathological effects of fractional CO2 laser on thermal burns in a controlled study. METHODS: Fifteen patients 11 with hypertrophic and four with keloidal scars received three CO2 fractional laser sessions every 4-6 weeks. Half of the scar was untreated as a control. Clinical evaluation by Vancouver, PSOAS scores, and photography before, monthly, and 3 months after the last laser session was performed. Ten patients were evaluated histopathologically by standard H&E, Masson trichrome, and Elastica von Gieson special stains. RESULTS: Hypertrophic scars (HTSs) showed textural improvement and a significant decrease of Vancouver, POSAS observer, and patient scores by the end of follow-up period in the laser-treated area (P = 0.011, 0.017 and 0.018, respectively) unlike keloidal scars. Histopathology revealed significant decrease in scar thickness in HTSs only (P < 0.001) as well as a significant decrease in collagen bundle thickness and density in the upper dermis in both types of scars. CONCLUSIONS: Fractional CO2 laser is a possible safe and effective modality for the treatment of hypertrophic burn scars with improvement achieved both clinically and histopathologically. PMID- 26260019 TI - Proximal Fugl-Meyer Assessment Scores Predict Clinically Important Upper Limb Improvement After 3 Stroke Rehabilitative Interventions. AB - OBJECTIVE: To identify the baseline motor characteristics of the patients who responded to 3 prominent intervention programs. DESIGN: Observational cohort study. SETTING: Outpatient rehabilitation clinics. PARTICIPANTS: Individuals with chronic stroke (N=174). INTERVENTIONS: Participants received 30 hours of constraint-induced movement therapy (CIMT), robot-assisted therapy, or mirror therapy (MT). MAIN OUTCOME MEASURES: The primary outcome measure was the change score of the Upper Extremity Fugl-Meyer Assessment (UE-FMA). The potential predicting variables were baseline proximal, distal, and total UE-FMA and Action Research Arm Test scores. We combined polynomial regression analyses and the minimal clinically important difference to stratify the patients as responders and nonresponders for each intervention approach. RESULTS: Baseline proximal UE FMA scores significantly predicted clinically important improvement on the primary outcome measure after all 3 interventions. Participants with baseline proximal UE-FMA scores of approximately <30 benefited significantly from CIMT and robot-assisted therapy, whereas participants with scores between 21 and 35 demonstrated significant improvement after MT. Baseline distal and total UE-FMA and Action Research Arm Test scores could also predict upper limb improvement after CIMT and MT, but not after robot-assisted therapy. CONCLUSIONS: This study could inform clinicians about the selection of suitable rehabilitation approaches to help patients achieve clinically meaningful improvement in upper extremity function. PMID- 26260020 TI - The Way Forward: Key Areas for Physiotherapy Research International. PMID- 26260021 TI - Fertility desire and associated factors among clients on highly active antiretroviral treatment at finoteselam hospital Northwest Ethiopia: a cross sectional study. AB - BACKGROUND: The accessibility of antiretroviral treatment changed the lives of persons living with HIV from hopelessness to hopefulness. Thus, many of them decided to have children. In Ethiopia, where there is high prevalence of HIV, level of fertility desire among persons living with HIV could have significant part in safe motherhood and child health. The aim of this study was to assess the level of fertility desire and identify factors associated with it among clients on highly active antiretroviral treatment at Finoteselam Hospital, Northwest Ethiopia. METHODS: A cross-sectional study design supplemented by in-depth interview was conducted on 422 clients on Highly Active Antiretroviral Treatment from July 1 to August 12, 2013. Structured questionnaire was used to collect the data. Data were entered in to EPi Info version 3.5.1 and exported to SPSS software version 16 for further analysis. Descriptive and summary statistics were computed. Proportions were calculated to estimate fertility desire level. Binary logistic regression model was fitted to identify factors associated with fertility desire. RESULTS: A total of 422 clients were included in the study of which 217 (51.4%) were males. The median age was 33 (IQR = 12) years. A total of 141(33.4%) of clients had desire for having children. Male clients desire children than their female counterparts [AOR = 3.19, 95 % CI: (1.56, 6.51)]. Clients who had no child had more desire for having children than those who had three or more children [AOR = 6.78, 95 % CI: (2.38, 19.27)] and those who had <=2 years duration on ART had more desire than those with >2 years duration on ART [AOR = 3.64, 95 % CI: (1.74, 7.64)]. Clients who had discussion with ART service provider about sexuality, Fertility desire and family planning had more child desire [AOR = 3.12, 95 % CI: (1.54, 6.32)]. CONCLUSIONS: One third of clients have desire to have a child/children in the future. Male clients and clients who have less than or equal to 2 years ART follow up, with no child and having discussion with ART service provider were associated with increased fertility desire. Guidelines formulated and counseling protocols developed shall consider this desire to achieve their reproductive goals in the healthiest and safest possible manner. PMID- 26260022 TI - Multinodule abnormalities of the tracheobronchus: bronchoscopy findings and clinical diagnosis. AB - BACKGROUND AND AIMS: Bronchoscopy is an important method for diagnosing respiratory disease. Multiple tracheobronchial nodules are rarely reported and their causes remain unclear. OBJECTIVES: The aim of this study was to describe the clinical characteristics of multiple nodule tracheobronchial abnormalities found under bronchoscopy caused by different diseases. METHODS: Eighty-seven patients with multiple tracheobronchial nodules were enrolled in this study. The characteristics of the multinodule lesions and the patient were diagnosed based on the pathology findings in our hospital. Chest computed tomography images were retrospectively reviewed by pulmonologists and radiologist. RESULTS: In 55 patients with definite pathological diagnosis, 16 (29%) patients were diagnosed as tuberculosis (TB) granuloma; 23 (41.8%) cases were diagnosed as malignant disease; 12 (21.8%) cases were diagnosed as tracheobronchopathia osteochondroplastica; 2 (3.6%) cases were diagnosed as sarcoidosis; and one case (1.8%) was diagnosed as lymphoma and one case (1.8%) as fungal infection. There were 32 cases of chronic inflammation. There was no relationship between nodule distribution and the pathological diagnosis. Malignant nodules usually smaller with a pale outlook, while nodules with larger size and smooth and intact mucosa usually turn out to be granuloma of unknown reason. CONCLUSION: The major causes of mutinodule lesions observed using bronchoscopy are tumor and TB. The presence of multiple endotracheobronchial nodules suggest that pulmonary lesion is present, and biopsy should be performed. Malignant nodules can be diagnosed by appearance and biopsy. Pathology results of TB, sarcoidosis and fungal infection can turn out to be granuloma of unknown reason. Further diagnosis needs other clinical materials. PMID- 26260023 TI - Improvement of Stability for Small Molecule Organic Solar Cells by Suppressing the Trap Mediated Recombination. AB - To understand the degradation mechanism of organic solar cells (OSCs), the charge dynamics of conventional and inverted planar heterojunction OSCs based on boron subthalocyanine chloride (SubPc) and fullerene (C60) with identical buffers during the air exposure were investigated. The results of light intensity dependent open circuit voltage show that the bimolecular recombination is dominated in the fresh devices, regardless of the device structure. The appearance of transient peak in photocurrent after turn-on and the light intensity independent turn-off traces in transient photocurrent suggest that the rapid degradation of conventional device is due to the energy loss originated from the aggravated trap mediated recombination. In contrast, the half-lifetime of inverted device is ~25 times longer than the conventional one. The improvement of stability is ascribed to the decrease of the trap generation possibility and the suppression of trap mediated recombination in the case of inverted structure, where the penetration of oxygen and water through buffer layer is avoided. PMID- 26260025 TI - Depletion force induced collective motion of microtubules driven by kinesin. AB - Collective motion is a fascinating example of coordinated behavior of self propelled objects, which is often associated with the formation of large scale patterns. Nowadays, the in vitro gliding assay is being considered a model system to experimentally investigate various aspects of group behavior and pattern formation by self-propelled objects. In the in vitro gliding assay, cytoskeletal filaments F-actin or microtubules are driven by the surface immobilized associated biomolecular motors myosin or dynein respectively. Although the F actin/myosin or microtubule/dynein system was found to be promising in understanding the collective motion and pattern formation by self-propelled objects, the most widely used biomolecular motor system microtubule/kinesin could not be successfully employed so far in this regard. Failure in exhibiting collective motion by kinesin driven microtubules is attributed to the intrinsic properties of kinesin, which was speculated to affect the behavior of individual gliding microtubules and mutual interactions among them. In this work, for the first time, we have demonstrated the collective motion of kinesin driven microtubules by regulating the mutual interaction among the gliding microtubules, by employing a depletion force among them. Proper regulation of the mutual interaction among the gliding microtubules through the employment of the depletion force was found to allow the exhibition of collective motion and stream pattern formation by the microtubules. This work offers a universal means for demonstrating the collective motion using the in vitro gliding assay of biomolecular motor systems and will help obtain a meticulous understanding of the fascinating coordinated behavior and pattern formation by self-propelled objects. PMID- 26260024 TI - The antioxidant compound tert-butylhydroquinone activates Akt in myocardium, suppresses apoptosis and ameliorates pressure overload-induced cardiac dysfunction. AB - Tert-butylhydroquinone (TBHQ) is an antioxidant compound which shows multiple cytoprotective actions. We evaluated the effects of TBHQ on pathological cardiac remodeling and dysfunction induced by chronic overload. Pressure overload was created by transverse aortic constriction (TAC) in male C57BL/6 mice. TBHQ was incorporated in the diet and administered for 4 weeks. TBHQ treatment prevented left ventricular dilatation and cardiac dysfunction induced by TAC, and decreased the prevalence of myocardial apoptosis. The beneficial effects of TBHQ were associated with an increase in Akt activation, but not related to activations of Nrf2 or AMP-activated protein kinase. TBHQ-induced Akt activation was accompanied by increased phosphorylation of Bad, glycogen synthase kinase-3beta (GSK-3beta) and mammalian target of rapamycin (mTOR). Mechanistically, we showed that in cultured H9c2 cells and primary cardiac myocytes, TBHQ stimulated Akt phosphorylation and suppressed oxidant-induced apoptosis; this effect was abolished by wortmannin or an Akt inhibitor. Blockade of the Akt pathway in vivo accelerated cardiac dysfunction, and abrogated the protective effects of TBHQ. TBHQ also reduced the reactive aldehyde production and protein carbonylation in stressed myocardium. We suggest that TBHQ treatment may represent a novel strategy for timely activation of the cytoprotective Akt pathway in stressed myocardium. PMID- 26260026 TI - Perceived discrimination and youths' adjustment: sleep as a moderator. AB - Adolescents' sleep duration was examined as a moderator of the association between perceived discrimination and internalizing (anxiety, depression) and externalizing symptoms. Participants were 252 adolescents (mean: 15.79 years; 66% European American, 34% African American) who reported on their perceived discrimination (racial and general) and adjustment. Sleep duration was measured using actigraphy. Moderation effects were evident. The lowest levels of internalizing symptoms were observed for adolescents with longer sleep duration in conjunction with lower levels of perceived racial discrimination. Further, general perceived discrimination was associated more strongly with externalizing behaviours for youth with shorter versus longer sleep. Findings highlight the importance of sleep as a bioregulatory system that can ameliorate or exacerbate the effects of discrimination on youths' adjustment. PMID- 26260028 TI - Ancestry and BMI Influences on Facial Soft Tissue Depths for A Cohort of Chinese and Caucasoid Women in Dunedin, New Zealand. AB - This study measured and assessed facial soft tissue depths (FSTDs) in adult female Chinese and New Zealand (NZ) Europeans (Caucasoids). Ultrasound was used to obtain depths at nine landmarks on 108 healthy subjects (51 Chinese, 57 NZ European), erect positioned, of same age group (18-29 years). Height and weight were also recorded. Statistical analysis focused on comparison of tissue depth between the two ancestry groups and the influence of Body Mass Index (BMI) (kg/m2). Results showed mean depth differences at Supra M2 and Infra M2 landmarks significantly greater for Chinese than Caucasoid women for all three BMI Classes (BMI<20, 20<=BMI<25, 25<=BMI<30), even BMI<20. For both groups BMI positively correlated with FSTD values at all landmarks except Labrale superius. This study enabled ancestry and BMI influence on FSTDs to be observed and compared for two distinct groups. Results add to knowledge about facial tissue depth variation. PMID- 26260027 TI - Palmitoylethanolamide reduces pain-related behaviors and restores glutamatergic synapses homeostasis in the medial prefrontal cortex of neuropathic mice. AB - BACKGROUND: Enhanced supraspinal glutamate levels following nerve injury are associated with pathophysiological mechanisms responsible for neuropathic pain. Chronic pain can interfere with specific brain areas involved in glutamate dependent neuropsychological processes, such as cognition, memory, and decision making. The medial prefrontal cortex (mPFC) is thought to play a critical role in pain-related depression and anxiety, which are frequent co-morbidities of chronic pain. Using an animal model of spared nerve injury (SNI) of the sciatic nerve, we assess bio-molecular modifications in glutamatergic synapses in the mPFC that underlie neuropathic pain-induced plastic changes at 30 days post-surgery. Moreover, we examine the effects of palmitoylethanolamide (PEA) administration on pain-related behaviours, as well as the cortical biochemical and morphological changes that occur in SNI animals. RESULTS: At 1 month, SNI was associated with mechanical and thermal hypersensitivity, as well as depression-like behaviour, cognitive impairments, and obsessive-compulsive activities. Moreover, we observed an overall glutamate synapse modification in the mPFC, characterized by changes in synaptic density proteins and amino acid levels. Finally, with regard to the resolution of pain and depressive-like syndrome in SNI mice, PEA restored the glutamatergic synapse proteins and changes in amino acid release. CONCLUSIONS: Given the potential role of the mPFC in pain mechanisms, our findings may provide novel insights into neuropathic pain forebrain processes and indicate PEA as a new pharmacological tool to treat neuropathic pain and the related negative affective states. Graphical Abstract Palmitoylethanolamide: a new pharmacological tool to treat neuropathic pain and the related negative affective states. PMID- 26260029 TI - Nucleoporin 35 regulates cardiomyocyte pH homeostasis by controlling Na+-H+ exchanger-1 expression. AB - The mammalian nuclear pore complex is comprised of ~ 30 different nucleoporins (Nups). It governs the nuclear import of gene expression modulators and the export of mRNAs. In cardiomyocytes, Na(+)-H(+) exchanger-1 (NHE1) is an integral membrane protein that exclusively regulates intracellular pH (pHi) by exchanging one intracellular H(+) for one extracellular Na(+). However, the role of Nups in cardiac NHE1 expression remains unknown. We herein report that Nup35 regulates cardiomyocyte NHE1 expression by controlling the nucleo-cytoplasmic trafficking of nhe1 mRNA. The N-terminal domain of Nup35 determines nhe1 mRNA nuclear export by targeting the 5'-UTR (-412 to -213 nt) of nhe1 mRNA. Nup35 ablation weakens the resistance of cardiomyocytes to an acid challenge by depressing NHE1 expression. Moreover, we identify that Nup35 and NHE1 are simultaneously downregulated in ischemic cardiomyocytes both in vivo and in vitro. Enforced expression of Nup35 effectively counteracts the anoxia-induced intracellular acidification. We conclude that Nup35 selectively regulates cardiomyocyte pHi homeostasis by posttranscriptionally controlling NHE1 expression. This finding reveals a novel regulatory mechanism of cardiomyocyte pHi, and may provide insight into the therapeutic strategy for ischemic cardiac diseases. PMID- 26260030 TI - Dynamic markers based on blood perfusion fluctuations for selecting skin melanocytic lesions for biopsy. AB - Skin malignant melanoma is a highly angiogenic cancer, necessitating early diagnosis for positive prognosis. The current diagnostic standard of biopsy and histological examination inevitably leads to many unnecessary invasive excisions. Here, we propose a non-invasive method of identification of melanoma based on blood flow dynamics. We consider a wide frequency range from 0.005-2 Hz associated with both local vascular regulation and effects of cardiac pulsation. Combining uniquely the power of oscillations associated with individual physiological processes we obtain a marker which distinguishes between melanoma and atypical nevi with sensitivity of 100% and specificity of 90.9%. The method reveals valuable functional information about the melanoma microenvironment. It also provides the means for simple, accurate, in vivo distinction between malignant melanoma and atypical nevi, and may lead to a substantial reduction in the number of biopsies currently undertaken. PMID- 26260031 TI - Siblings' experiences of their brother's or sister's cancer death: a nationwide follow-up 2-9 years later. AB - OBJECTIVE: The aim of this study was to examine siblings' experiences of their brother's or sister's cancer death and if these experiences influenced levels of anxiety 2-9 years later. METHODS: This nationwide survey was conducted in Sweden in 2009. All siblings who had a brother/sister who was diagnosed with cancer before the age of 17 years and who died before the age of 25 years during 2000 2007 were invited. Of those, 174 siblings participated (participation rate: 73%). Mixed data from the survey about the siblings' experiences of death were included as well as data from the Hospital Anxiety and Depression Scale. To examine the experiences, descriptive statistics and content analysis were used. Mann-Whitney U-test was conducted to investigate if the experiences influenced anxiety 2-9 years later. RESULTS: The siblings reported poor knowledge and experienced a lack of communication about their brother's/sister's death, for example, about the time frame, bodily changes near death, and about their own experiences. Siblings who reported that no one talked with them about what to expect when their brother/sister was going to die reported higher levels of anxiety 2-9 years after the loss. Seventy percent reported that they witnessed their brother/sister suffering in the last hours in life. Many of those who were not present during the illness period and at the time of death expressed regret. CONCLUSION: It is important to prepare siblings for their brother's/sister's illness and death as it may decrease anxiety and regrets later on. PMID- 26260032 TI - Genetically engineered fusion of MAP-1 and factor H domains 1-5 generates a potent dual upstream inhibitor of both the lectin and alternative complement pathways. AB - Inhibition of the complement cascade has emerged as an option for treatment of a range of diseases. Mannose-binding lectin/ficolin/collectin-associated protein (MAP-1) is a pattern recognition molecule (PRM)-associated inhibitor of the lectin pathway. The central regulator of the alternative pathway (AP) is complement factor H (FH). Our aim was to design a dual upstream inhibitor of both human lectin and APs by fusing MAP-1 with a part of FH. There were 2 different recombinant chimeric proteins comprising full-length human MAP-1 and the first 5 N-terminal domains of human FH designed. The FH domains were orientated either in the N- or C-terminal part of MAP-1. The complement inhibition potential in human serum was assessed. Both chimeric constructs displayed the characteristics of the native molecules and bound to the PRMs with an EC50 of ~ 2 nM. However, when added to serum diluted 1:4 in a solid-phase functional assay, only the first 5 N terminal domains of complement FH fused to the C-terminal part of full-length MAP 1 chimeric construct were able to combine inhibition of lectin and AP activation with an half maximal inhibitory concentration of ~ 100 and 20 nM, respectively. No effect was seen on the classical pathway. Fusion of MAP-1 with FH domains represents a novel therapeutic approach for selective targeting upstream and central complement activation at sites of inflammation. PMID- 26260033 TI - Circadian desynchronization triggers premature cellular aging in a diurnal rodent. AB - Chronic jet lag or shift work is deleterious to human metabolic health, in that such circadian desynchronization is associated with being overweight and the prevalence of altered glucose metabolism. Similar metabolic changes are observed with age, suggesting that chronic jet lag and accelerated cell aging are intimately related, but the association remains to be determined. We addressed whether jet lag induces metabolic and cell aging impairments in young grass rats (2-3 mo old), using control old grass rats (12-18 mo old) as an aging reference. Desynchronized young and control old subjects had impaired glucose tolerance (+60 and +280%) when compared with control young animals. Despite no significant variation in liver DNA damage, shorter telomeres were characterized, not only in old animal liver cells (-18%), but also at an intermediate level in desynchronized young rats (-9%). The same pattern was found for deacetylase sirtuin (SIRT)-1 (-57 and -29%), confirming that jet-lagged young rats have an intermediate aging profile. Our data indicate that an experimental circadian desynchronization in young animals is associated with a precocious aging profile based on 3 well-known markers, as well as a prediabetic phenotype. Such chronic jet lag-induced alterations observed in a diurnal species constitute proof of principle of the need to develop preventive treatments in jet-lagged persons and shift workers. PMID- 26260034 TI - HSF2 autoregulates its own transcription. AB - Heat shock factor 2 (HSF2) is one of the most important regulators affecting stress mechanisms, and is frequently amplified in the ubiquitin proteasome pathway. Despite its significance, the mechanisms which regulate HSF2 expression remain unclear. In the present study, we describe the existence of a negative autoregulatory mechanism of HSF2. Transfection assays demonstrated that HSF2 decreased endogenous HSF2 mRNA expression in human K562 erythroleukemia cells. Luciferase reporter assays revealed that HSF2 inhibited the activity of its own promoter in a dose-dependent manner and that the downstream region (-1.5 kb) relative to the transcription start site was responsible for this inhibitory effect. Furthermore, chromatin immunoprecipitation (ChIP) assat indicated that HSF2 is directly recruited onto its own promoter, which contains a putative heat shock element (HSE). Collectively, the findings of our studys suggest that HSF2 contributes to its own expression by forming a negative autoregulatory loop. PMID- 26260035 TI - Relationships between paranoid thinking, self-esteem and the menstrual cycle. AB - This study aimed to investigate whether paranoid experiences and levels of self esteem fluctuate over the menstrual cycle and whether levels of self-esteem are lower when perceived persecution is felt to be deserved. Measures of anxiety, depression, persecution, deservedness and self-esteem were completed on-line by 278 women over their menstrual cycle. Responses were compared at the paramenstrual (3 days before and after menses onset) and mid-cycle phase. At the paramenstrual phase persecution, negative self-esteem, anxiety and depression were higher and positive self-esteem was lower than at mid-cycle. A greater proportion of women experienced persecution as deserved at the paramenstrual phase. This was associated with higher depression and negative self-esteem scores. Increased levels of deservedness significantly strengthened the relationship between persecution and negative, but not positive, self-esteem. These findings suggest that the paramenstrual phase is a time of vulnerability to increased paranoid experiences, an increased likelihood that feelings of persecution will feel deserved and lowered self-esteem. The findings support the view that interpersonal sensitivities may be key to menstrual cycle symptoms and have an impact on relationships. Further, the study illustrated that ideas developed for psychosis could make a valuable contribution to understanding and managing this aspect of menstruation-related distress. PMID- 26260036 TI - Perinatal psychosis in mothers with a history of major depressive disorder. AB - While women with a history of major depressive disorder (MDD) have higher chances for postpartum depressive and manic episodes, little is known about their chance for postpartum psychosis (PPP). We prospectively assessed the frequency of perinatal psychotic symptoms among primiparous women with a history of MDD only (structured clinical interview was used to exclude women with pre-existing histories of mania or psychosis) and explored whether sex of the baby influenced these symptoms.The presence of symptoms of psychosis was defined using previously established cutoff scores on five key items from the Positive and Negative Syndrome Scale (PANSS), which was administered during pregnancy, at 1 week, 1 month, and 3 months postpartum.Fourteen of 60 women (23%) scored above threshold for psychosis at one or more time points, with 6 experiencing postpartum onset. There was a non-significant trend (p = 0.073) towards higher frequency of these symptoms among mothers of girls.If controlled studies using diagnostic interviews confirm that psychotic symptoms are relatively common among women with MDD, monitoring for psychosis during the perinatal period may be indicated in this population. The potential effect of sex of the baby on mothers' chance for PPP requires further study. PMID- 26260037 TI - The comparative effects of group prenatal care on psychosocial outcomes. AB - To compare the psychosocial outcomes of the CenteringPregnancy (CP) model of group prenatal care to individual prenatal care, we conducted a prospective cohort study of women who chose CP group (N = 124) or individual prenatal care (N = 124). Study participants completed the first survey at study recruitment (mean gestational age 12.5 weeks), with 89% completing the second survey (mean gestational age 32.7 weeks) and 84% completing the third survey (6 weeks' postpartum). Multiple linear regression models compared changes by prenatal care model in pregnancy-specific distress, prenatal planning-preparation and avoidance coping, perceived stress, affect and depressive symptoms, pregnancy-related empowerment, and postpartum maternal-infant attachment and maternal functioning. Using intention-to-treat models, group prenatal care participants demonstrated a 3.2 point greater increase (p < 0.05) in their use of prenatal planning preparation coping strategies. While group participants did not demonstrate significantly greater positive outcomes in other measures, women who were at greater psychosocial risk benefitted from participation in group prenatal care. Among women reporting inadequate social support in early pregnancy, group participants demonstrated a 2.9 point greater decrease (p = 0.03) in pregnancy specific distress in late pregnancy and 5.6 point higher mean maternal functioning scores postpartum (p = 0.03). Among women with high pregnancy specific distress in early pregnancy, group participants had an 8.3 point greater increase (p < 0.01) in prenatal planning-preparation coping strategies in late pregnancy and a 4.9 point greater decrease (p = 0.02) in postpartum depressive symptom scores. This study provides further evidence that group prenatal care positively impacts the psychosocial well-being of women with greater stress or lower personal coping resources. Large randomized studies are needed to establish conclusively the biological and psychosocial benefits of group prenatal care for all women. PMID- 26260038 TI - Changing mothers' perception of infant emotion: a pilot study. AB - Cognitive bias modification (CBM) techniques, which experimentally retrain abnormal processing of affective stimuli, are becoming established for various psychiatric disorders. Such techniques have not yet been applied to maternal processing of infant emotion, which is affected by various psychiatric disorders. In a pilot study, mothers of children under 3 years old (n = 2) were recruited and randomly allocated to one of three training exercises, aiming either to increase or decrease their threshold of perceiving distress in a morphed continuum of 15 infant facial images. Differences between pre- and post-training threshold were analysed between and within subjects. Compared to baseline thresholds, the threshold for perceiving infant distress decreased in the lowered threshold group (mean difference -1.7 frames, 95 % confidence intervals (CI) -3.1 to -0.3, p = 0.02), increased in the raised threshold group (1.3 frames, 95 % CI 0.6 to 2.1, p < 0.01) and was unchanged in the control group (0.1 frames, 95 % CI -0.8 to 1.1, p = 0.80). Between-group differences were similarly robust in regression models and were not attenuated by potential confounders. The findings suggest that it is possible to change the threshold at which mothers perceive ambiguous infant faces as distressed, either to increase or decrease sensitivity to distress. This small study was intended to provide proof of concept (i.e. that it is possible to alter a mother's perception of infant distress). Questions remain as to whether the effects persist beyond the immediate experimental session, have an impact on maternal behaviour and could be used in clinical samples to improve maternal sensitivity and child outcomes. PMID- 26260039 TI - Does surgery have a role in managing incurable gastric cancer? AB - Although the incidence of gastric cancer is decreasing, the outcomes of this disease are among the poorest of all solid-organ tumours, predominantly due to the frequent presence of stage IV metastatic disease at primary presentation. Stage IV gastric cancer is incurable and carries a very poor prognosis (5-year survival rate of ~4%); palliative chemotherapy remains the standard of care, but increasing evidence indicates that palliative surgery can provide a prognostic and symptomatic benefit, particularly in combination with chemotherapy and/or radiotherapy. Ongoing prospective trials should further clarify the efficacy of palliative surgery in comparison with other treatment modalities. Until such data are available, surgery should not be offered as a standard first-line treatment, but can be considered in selected cases after thorough multidisciplinary discussions involving the patient. Patient selection for both gastrectomy and nonresectional surgery must include consideration of various factors that predict quality of life after surgery. This Perspectives summarizes the available evidence and discusses the utility of palliative surgery in relation to other therapeutic modalities in the management of incurable gastric cancer. PMID- 26260040 TI - Breast cancer: weekly paclitaxel--still preferred first-line taxane for mBC. PMID- 26260041 TI - Imaging: improving detection of bone metastases in renal cell carcinoma. PMID- 26260042 TI - Haematological cancer: promising results of BCL2 inhibition. PMID- 26260043 TI - Improving diabetes outcomes through lifestyle change--A randomized controlled trial. AB - OBJECTIVE: To compare a diabetes group lifestyle intervention (GLI) with dietitian referral for medical nutrition therapy (RD) for weight loss in the usual care setting. METHODS: Randomized clinical trial was conducted with 57 primary care patients with type 2 diabetes and body mass index (BMI) >25 kg/m(2) who received either a dietitian-led 19-week GLI adapted from the Look AHEAD study or RD. Outcome measures include 6-month and 1-year weight loss, changes in medications, glycemic control, cardiac risk factors, and cost analysis. RESULTS: Patients were mean age 61, 59% male, and 32% non-white, and they weighed 97 kg with mean HbA1c 8.2%. At 6 months, 46% of GLI vs. 21% of RD lost >=5% body weight (P = 0.04), with mean weight loss 6.6 (SD 7.0) kg with GLI and 2.1 (3.5) kg in RD (P = 0.004). HbA1c improved by 0.70 (1.13) vs. 0.39 (1.51) in GLI vs. RD (P = 0.4), respectively, and 82% vs. 38% stopped or reduced diabetes medications (P < 0.001). Weight loss remained significantly greater in GLI compared to RD at 1 year. GLI program cost was $578 per participant. CONCLUSIONS: An affordable GLI achieved significantly more weight loss and medication reduction than RD in primary care patients with type 2 diabetes. PMID- 26260044 TI - IL-Y, a synthetic member of the IL-12 cytokine family, suppresses the development of type 1 diabetes in NOD mice. AB - The IL-12 family of heterodimeric cytokines, consisting of IL-12, IL-23, IL-27, and IL-35, has important roles in regulating the immune response. IL-12 family members are comprised of a heterodimer consisting of alpha and beta chains: IL-12 (p40 and p35), IL-23 (p40 and p19), IL-27 (Ebi3 and p28), and IL-35 (Ebi3 and p35). Given the combinatorial nature of the IL-12 family, we generated adenoviral vectors expressing two putative IL-12 family members not yet found naturally, termed IL-X (Ebi3 and p19) and IL-Y (p40 and p28), as single-chain molecules. Single chain IL-Y (scIL-Y), but not scIL-X, was able to stimulate significantly a unique cytokine/chemokine expression profile as well as activate STAT3 in mice, in part, through a pathway involving IL-27Ralpha in splenocytes. Adenoviral mediated, intratumoral delivery of scIL-Y increased tumor growth in contrast to the anti-tumor effects of scIL-12 and scIL-23. Similarly, treatment of prediabetic NOD mice by intravenous injection of Ad.scIL-Y prevented the onset of hyperglycemia. Analysis of cells from Ad.scIL-Y-treated NOD mice demonstrated that scIL-Y reduced expression of inflammatory mediators such as IFN-gamma. Our data demonstrate that a novel, synthetic member of the IL-12 family, termed IL-Y, confers unique immunosuppressive effects in two different disease models and thus could have therapeutic applications. PMID- 26260046 TI - The Evaluation of Curative Effect of Acupuncture: A Review of Systematic and Meta Analysis Studies. AB - The present study attempts to critically evaluate previously published research articles on the efficiency of acupuncture in the treatment of diseases. First, 35 systematic reviews or meta-analysis were found in the Cochrane database. Second, 54 related articles were selected by searching important scientific databases. Based on the results obtained regarding the efficacy of acupuncture for the treatment of various diseases, the articles were divided into 3 groups. The first group of articles confirmed the efficacy of treatment by acupuncture. In the second group of articles, the therapeutic effect of acupuncture was shown; however, further research is required to verify the results. In the third group of articles there is no evidence regarding the therapeutic effect of acupuncture till now. There is an urgent need to design and conduct double-blinded randomized clinical trials with high-quality methodologies. This provides a more careful evaluation of acupuncture efficiency in relation to the treatment of a vast array of diseases, based on scientific evidence. PMID- 26260045 TI - Treatment of Atopic Dermatitis From the Perspective of Traditional Persian Medicine: Presentation of a Novel Therapeutic Approach. AB - There is a strong current trend for using complementary and alternative medications to treat atopic dermatitis. Atopic dermatitis is a common, chronic, pruritic, and inflammatory skin disease. It can have a profound, negative effect on patients' quality of life. Mild cases of atopic dermatitis can be controlled by the application of moisturizers and topical corticosteroids. However, in severe cases, application of immunosuppressive medication is unavoidable but it can have adverse effects. In traditional Persian medicine, diseases similar to resistant atopic dermatitis are treated with whey in combination with decoction of field dodder. Both whey and field dodder have anti-inflammatory properties. Consumption of whey can also aid skin repair, mitigate pruritus, and help combat the high level of stress experienced by patients. Therefore, it is hypothesized that consumption of traditional medicinal treatment of whey with decoction of field dodder can be applied as a complementary treatment for atopic dermatitis. PMID- 26260047 TI - Influence of Coprecipitated Organic Matter on Fe2+(aq)-Catalyzed Transformation of Ferrihydrite: Implications for Carbon Dynamics. AB - Aqueous Fe(II) is known to catalyze the abiotic transformation of ferrihydrite to more stable Fe minerals. However, little is known about the impacts of coprecipitated OM on Fe(II)-catalyzed ferrihydrite transformation and its consequences for C dynamics. Accordingly, we investigated the extent and pathway of Fe(II)-induced transformation of OM-ferrihydrite coprecipitates as a function of C/Fe ratios and aqueous Fe(II) concentrations, and its implications for subsequent C dynamics. The coprecipitated OM resulted in a linear decrease in ferrihydrite transformation with increasing C/Fe ratios. The secondary mineral profiles upon Fe(II) reaction with OM-ferrihydrite coprecipitates depend on Fe(II) concentrations At 0.2 mM Fe(II), OM completely inhibited goethite formation and stimulated lepidocrocite formation. At 2 mM Fe(II), whereas goethite was formed in the presence of OM, OM reduced the amount of goethite and magnetite formation and increased the formation of lepidocrocite. The solid-phase C content remained unchanged after reaction, suggesting that OM remains associated with Fe minerals following ferrihydrite transformation to more stable Fe minerals. However, C desorbability by H2PO4(-) from the resulting Fe minerals following reaction was enhanced. The study indicates a "lepidocrocite favoring effect" by OM and suggests that Fe(II)-catalyzed transformation of ferrihydrite may decrease OM stability in natural environments under moderately reducing conditions. PMID- 26260048 TI - Applying the food multimix concept for sustainable and nutritious diets. AB - Despite a rich and diverse ecosystem, and biodiversity, worldwide, more than 2 billion people suffer from micronutrient malnutrition or hidden hunger. Of major concern are a degradation of our ecosystems and agricultural systems which are thought to be unsustainable thereby posing a challenge for the future food and nutrition security. Despite these challenges, nutrition security and ensuring well balanced diets depend on sound knowledge and appropriate food choices in a complex world of plenty and want. We have previously reported on how the food multimix (FMM) concept, a food-based and dietary diversification approach can be applied to meet energy and micronutrient needs of vulnerable groups through an empirical process. Our objective in this paper is to examine how the concept can be applied to improve nutrition in a sustainable way in otherwise poor and hard to-reach communities. We have reviewed over 100 FMM food recipes formulated from combinations of commonly consumed traditional candidate food ingredients; on average five per recipe, and packaged as per 100 g powders from different countries including Ghana, Kenya, Botswana, Zimbabawe and Southern Africa, India, Mexico, Malaysia and the UK; and for different age groups and conditions such as older infants and young children, pregnant women, HIV patients, diabetes and for nutrition rehabilitation. Candidate foods were examined for their nutrient strengths and nutrient content and nutrient density of recipes per 100 g were compared with reference nutrient intakes for the different population groups. We report on the nutrient profiles from our analysis of the pooled and age-matched data as well as sensory analysis and conclude that locally produced FMM foods can complement local diets and contribute significantly to meet nutrient needs among vulnerable groups in food-insecure environments. PMID- 26260049 TI - Pollution distribution and health risk assessment of heavy metals in indoor dust in Anhui rural, China. AB - Zn, Pb, Cu, Cr, V, Ni, Co, and As concentrations of indoor dust in Anhui rural were determined by inductively coupled plasma-optical emission spectroscopy (ICP OES). The degrees of metal pollution in indoor dust ranked as follows: Zn > Pb > Cr > Cu > V > Ni > Co > As, on average. The arithmetic means of Zn, Pb, Cu, Cr, V, Ni, Co, and As were 427.17, 348.73, 107.05, 113.68, 52.64, 38.93, 10.29, and 4.46 mg/kg, respectively. These were higher than background values of Anhui soil for Zn, Pb, Cu, Cr, and Ni, especially for Pb with the mean value of 13.21 times the background value. Heavy metal concentrations of indoor dust were different from different rural areas. House type (bungalows or storied house), sweeping frequency, and external environment around the house (such as the road grade) affected heavy metal concentrations in indoor dust. The results of factor analysis and correlation analysis indicated that Cu, Cr, Ni, Zn, and Co concentrations were mainly due to interior paint, metal objects, and building materials. Pb and As concentrations were due to vehicle emissions. V concentration was mainly of natural source. Average daily doses for the exposure pathway of the studied heavy metals decreased in children in the following order: hand-to-mouth ingestion > dermal contact > inhalation. The non-carcinogenic risks of heavy metals ranked as Pb > V > Cr > Cu > Zn > As > Co > Ni, and the carcinogenic risks of metals decreased in the order of Cr > Co > As > Ni. The non carcinogenic hazard indexes and carcinogenic risks of metals in indoor dust were both lower than the safe values. PMID- 26260050 TI - Direct localisation of molecules in tissue sections of growing antler tips using MALDI imaging. AB - The astonishing growth rate of deer antlers offers a valuable model for the discovery of novel factors and regulatory systems controlling rapid tissue growth. Numerous molecules have been identified in growing antlers using a variety of techniques. However, little is known about the spatial distribution of these molecules in situ. A technique that has the potential to help in this regard is direct proteomic analysis of tissue sections by matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS). The present study applied this technique to spatially map molecules in antler tissue sections. Two protonated molecular ions were selected: m/z 6679 and m/z 6200 corresponding to VEGF and thymosin beta-10, respectively. Superimposition of the respective ion images on to histologically stained samples showed distinct spatial distribution across the antler tissue sections which were consistent with the previous reports using in situ hybridization. Two other molecular ions specifically m/z 8100 and m/z 11,800 were also selected, corresponding to reported masses of urocortin precursor and thioredoxin, respectively. As the spatial distribution of these proteins is not specifically known, MALDI-IMS was used as a potential technique to obtain information on their distribution on antler tips. The presence of all these molecules in deer antlers were further confirmed using LC-MS/MS data. The present study also demonstrated that MALDI-IMS could be further used to image antler sections with an extended ion mass range of up to m/z 45,000, thus potentially increasing the ability to discover the distribution of a larger set of molecules that may play an important role in antler growth. We have thus demonstrated that MALDI-IMS is a promising technique for generating molecular maps with high spatial resolution which can aid in evaluating the function of novel molecules during antler growth. PMID- 26260051 TI - Leukocyte integrin alpha4beta7 associates with heat shock protein 70. AB - The leukocyte integrin cell adhesion molecules alpha4beta7 and alphaEbeta7 mediate the homing and retention of lymphocytes to the gut, and sites of inflammation. Here we have identified heat shock protein 70 (HSP70) as a major protein that associates with the cytoplasmic domain of the integrin beta7 subunit. HSPs are molecular chaperones that protect cells from stress but more recently have been reported to also regulate cell adhesion and invasion via modulation of beta1, beta2, and beta3 integrins and integrin-associated signalling molecules. Several HSP70 isoforms including HSP70-3, HSP70-1L, HSP70 8, and HSP70-9 were specifically precipitated from T cells by a bead-conjugated beta7 subunit cytoplasmic domain peptide and subsequently identified by high resolution liquid chromatography-tandem mass spectrometry. In confirmation, the beta7 subunit was co-immunoprecipitated from a T cell lysate by an anti-HSP70 antibody. Further, recombinant human HSP70-1a was precipitated by beta7 cytoplasmic domain-coupled beads. The HSP70 inhibitor KNK437 decreased the expression of HSP70 without affecting the expression of the beta7 integrin. It significantly inhibited alpha4beta7-mediated adhesion of T cells to mucosal addressin cell adhesion molecule 1 (MAdCAM-1), suggesting HSP70 is critical for maintaining beta7 integrin signalling function. The functional implications of the association of beta7 integrins with the different isoforms of HSP70 warrants further investigation. PMID- 26260052 TI - Overexpression of SYF2 correlates with enhanced cell growth and poor prognosis in human hepatocellular carcinoma. AB - SYF2, also known as p29/NTC31/CBPIN, encodes a nuclear protein that interacts with Cyclin D-type binding-protein 1. SYF2 has been reported to be involved in pre-mRNA splicing and cell cycle regulation. In the present study, we observed that SYF2 was obviously upregulated in HCC tumor tissues and cell lines, and its level was positively correlated with the tumor grade and Ki-67 expression, as well as poor prognosis of HCC. In vitro, using serum starvation-refeeding experiment, our results suggested that SYF2 was upregulated in proliferating HCC cells, and was positive correlated with the expression of PCNA and Cyclin D1. In addition, depletion of SYF2 decreased PCNA and Cyclin D1 levels. Accordingly, interference of SYF2 resulted in cells cycle arrest at G1/S phase in Huh7 HCC cells. Furthermore, we found that SYF2 might interact with Cyclin D1 and could confer doxorubicin resistance in HCC cells. These findings revealed that SYF2 might play a regulatory role in the proliferation of HCC cells. In summary, SYF2 may be a novel prognostic marker and serve as a potential therapeutic target in HCC. PMID- 26260053 TI - Sulfuretin induces osteoblast differentiation through activation of TGF-beta signaling. AB - The identification and examination of potential determinants controlling the progression of cell fate toward osteoblasts can be intriguing subjects. In this study, the effects of sulfuretin, a major compound isolated from Rhus verniciflua Stokes, on osteoblast differentiation were investigated. Treatments of sulfuretin induced alkaline phosphatase (ALP) activity in mesenchymal C3H10T1/2 cells and mineralization in preosteoblast MC3T3-E1 cells. Pro-osteogenic effects of sulfuretin were consistently observed in freshly isolated primary bone marrow cells. In mechanical studies, sulfuretin specifically induced expression of TGF beta target genes, such as SMAD7 and PAI-1, but not other signaling pathway related genes. Similar to the results of gene expression analysis, reporter assays further demonstrated TGF-beta-specific induction by sulfuretin. Furthermore, disruption of TGF-beta signaling using treatment with TGF-beta specific inhibitor, SB-431542, and introduction of SMAD2/3 small interfering RNA impaired the effects of sulfuretin in inducing ALP activity and expression of ALP mRNA. Together, these data indicate that the pro-osteogenic effects of sulfuretin are mediated through activation of TGF-beta signaling, further supporting the potential of sulfuretin in the prevention of bone-related diseases such as bone fracture and osteoporosis. PMID- 26260054 TI - Impaired Myocardial Oxygenation Response to Stress in Patients With Chronic Kidney Disease. AB - BACKGROUND: Coronary artery disease and left ventricular hypertrophy are prevalent in the chronic kidney disease (CKD) and renal transplant (RT) population. Advances in cardiovascular magnetic resonance (CMR) with blood oxygen level-dependent (BOLD) technique provides capability to assess myocardial oxygenation as a measure of ischemia. We hypothesized that the myocardial oxygenation response to stress would be impaired in CKD and RT patients. METHODS AND RESULTS: Fifty-three subjects (23 subjects with CKD, 10 RT recipients, 10 hypertensive (HT) controls, and 10 normal controls without known coronary artery disease) underwent CMR scanning. All groups had cine and BOLD CMR at 3 T. The RT and HT groups also had late gadolinium CMR to assess infarction/replacement fibrosis. The CKD group underwent 2-dimensional echocardiography strain to assess fibrosis. Myocardial oxygenation was measured at rest and under stress with adenosine (140 MUg/kg per minute) using BOLD signal intensity. A total of 2898 myocardial segments (1200 segments in CKD patients, 552 segments in RT, 480 segments in HT, and 666 segments in normal controls) were compared using linear mixed modeling. Diabetes mellitus (P=0.47) and hypertension (P=0.57) were similar between CKD, RT, and HT groups. The mean BOLD signal intensity change was significantly lower in the CKD and RT groups compared to HT controls and normal controls (-0.89+/-10.63% in CKD versus 5.66+/-7.87% in RT versus 15.54+/-9.58% in HT controls versus 16.19+/-11.11% in normal controls, P<0.0001). BOLD signal intensity change was associated with estimated glomerular filtration rate (beta=0.16, 95% CI=0.10 to 0.22, P<0.0001). Left ventricular mass index and left ventricular septal wall diameter were similar between the CKD predialysis, RT, and HT groups. None of the CKD patients had impaired global longitudinal strain and none of the RT group had late gadolinium hyperenhancement. CONCLUSIONS: Myocardial oxygenation response to stress is impaired in CKD patients and RT recipients without known coronary artery disease, and unlikely to be solely accounted for by the presence of diabetes mellitus, left ventricular hypertrophy, or myocardial scarring. The impaired myocardial oxygenation in CKD patients may be associated with declining renal function. Noncontrast BOLD CMR is a promising tool for detecting myocardial ischemia in the CKD population. PMID- 26260056 TI - Erratum to: Benefits of applying a proxy eligibility period when using electronic health records for outcomes research: a simulation study. PMID- 26260055 TI - Effect of mushroom Agaricus blazei on immune response and development of experimental cerebral malaria. AB - BACKGROUND: Cerebral malaria (CM) is debilitating and sometimes fatal. Disease severity has been associated with poor treatment access, therapeutic complexity and drug resistance and, thus, alternative therapies are increasingly necessary. In this study, the effect of the administration of Agaricus blazei, a mushroom of Brazilian origin in a model of CM caused by Plasmodium berghei, strain ANKA, was investigated in mice. METHODS: C57BL/6 mice were pre-treated with aqueous extract or fractions of A. blazei, or chloroquine, infected with P. berghei ANKA and then followed by daily administration of A. blazei or chloroquine. Parasitaemia, body weight, survival and clinical signs of the disease were evaluated periodically. The concentration of pro-and anti-inflammatory cytokines, histopathology and in vitro analyses were performed. RESULTS: Mice treated with A. blazei aqueous extract or fraction C, that shows antioxidant activity, displayed lower parasitaemia, increased survival, reduced weight loss and protection against the development of CM. The administration of A. blazei resulted in reduced levels of TNF, IL-1beta and IL-6 production when compared to untreated P. berghei-infected mice. Agaricus blazei (aqueous extract or fraction C) treated infected mice displayed reduction of brain lesions. Although chloroquine treatment reduced parasitaemia, there was increased production of proinflammatory cytokines and damage in the CNS not observed with A. blazei treatment. Moreover, the in vitro pretreatment of infected erythrocytes followed by in vivo infection resulted in lower parasitaemia, increased survival, and little evidence of clinical signs of disease. CONCLUSIONS: This study strongly suggests that the administration of A. blazei (aqueous extract or fraction C) was effective in improving the consequences of CM in mice and may provide novel therapeutic strategies. PMID- 26260057 TI - A mixed methods study of collaboration between perinatal and infant mental health clinicians and other service providers: Do they sit in silos? AB - BACKGROUND: Women at risk of poor perinatal mental health benefit from coordinated approaches to care. Perinatal and infant mental health (PIMH) services have been established to support women with social and emotional needs. This paper examines the nature and extent of collaboration within two PIMH services in Australia. METHODS: A convergent, embedded, mixed methods design was used. Two hundred and forty four medical records were reviewed, 13 professionals (six PIMH clinicians, two PIMH service managers, and five key stakeholders) and 11 women service-users participated in semi-structured interviews. RESULTS: Three broad themes were drawn from the data, Theme 1: We don't sit in silos ... but they do, Theme 2: We need to enhance communication, and Theme 3: Collaboration is hard work. Perinatal and infant mental health clinicians believe they work collaboratively with other service providers. Key stakeholders and documentation in the medical records reveal that collaboration is nominal. CONCLUSIONS: Professionals believe that collaboration is essential for women with complex needs. Perinatal and infant mental health clinicians are skilled at building relationships with women, however further support is needed to build trusting relationships with other service providers. Women service-users also need to be involved in the collaborative process to become equal partners in their care. PMID- 26260058 TI - Two novel genetic variants in the mineralocorticoid receptor gene associated with spontaneous preterm birth. AB - BACKGROUND: Preterm birth is the leading cause of mortality and morbidity in newborn infants. Its etiology is multifactorial with genes and environmental factors, including chronic maternal stress, contributing to its risk. Our objective was to investigate whether single nucleotide polymorphisms (SNPs) in genes involved in the stress response are associated with spontaneous preterm birth using a candidate gene approach. METHODS: A total of 210 cases (singleton spontaneous preterm birth at <37 weeks) and 412 controls (singleton term birth at 38-42 weeks without a history of preterm birth) were studied. High quality maternal DNA was available from saliva samples of 190 cases and 369 controls and compared. Sociodemographic and medical data were collected. Sixteen SNPs, either tag SNPs located in key genes involved in the stress response identified in the Preterm Birth Genome Project database or SNPs found to be associated with adverse mental health outcomes in the published literature, were selected for genotyping and sequencing. SNPs were genotyped using Taqman SNP genotyping assays. Univariate and multivariate logistic regression were performed. RESULTS: Multivariate analysis showed that two SNPs located in the mineralocorticoid receptor gene were significantly associated with spontaneous preterm birth: rs17484063 (OR 0.50, p = 0.038) and rs2883929 (OR 0.49, p = 0.017), regardless of maternal age, smoking, alcohol use, educational status, and history of spontaneous miscarriage. CONCLUSION: This report demonstrates an association between mineralocorticoid receptor gene polymorphisms, rs17484063 and rs2883929, and preterm birth, supporting a role for genetics in the association between chronic maternal stress and preterm birth. Potentially, this information may be used to predicting the risk of having a preterm delivery. PMID- 26260059 TI - Nuclear organization of the rock hyrax (Procavia capensis) amygdaloid complex. AB - The current study details the nuclear organization of the rock hyrax amygdaloid complex using both Nissl and myelin stains, along with a range of immunohistochemical stains. The rock hyrax appears to be the least derived of the Afrotherians, a group with a huge range of body phenotypes, life histories and specialized behaviours, brain sizes, and ecological niches. In this sense, the rock hyrax represents a species where the organization of the amygdaloid complex may be reflective of that in stem Eutherian mammals. Our analysis indicates that the nuclear organization of the rock hyrax amygdaloid complex is indeed very similar to that in other mammals studied, with four major nuclear groupings (the deep or basolateral group; the superficial or cortical-like or corticomedial group; the centromedial group; and the other amygdaloid nuclei) being observed, which is typical of Eutherian mammals. Moreover, each of these groupings is composed of several nuclei, the vast majority of which were readily identified in the rock hyrax. Small nuclei identified in rodents and primates were absent in the superficial and centromedial groups, seemingly involved with olfaction. A novel shell-like nucleus of the accessory basal nuclear cluster was observed in the rock hyrax, again, likely to be involved in olfaction. The current study underlines the conserved nature of nuclear parcellation in the Eutherian mammal amygdaloid complex and indicates that across most species, the flow of information processing related to species-specific affective-laden stimuli and the resultant physiological and behavioural outcomes are likely to be similar across species. PMID- 26260060 TI - Comparison of bacterial diversity in full scale anammox bioreactors operated under different conditions. AB - Bacterial community structure of full-scale anammox bioreactor is still mainly unknown. It has never been analyzed whether different anammox bioreactor configurations might result in the development of different bacterial community structures among these systems. In this work, the bacterial community structure of six full-scale autotrophic nitrogen removal bioreactors located in The Netherlands and China operating under three different technologies and with different influent wastewater characteristics was studied by the means of pyrotag sequencing evaluation of the bacterial assemblage yielded a great diversity in all systems. The most represented phyla were the Bacteroidetes and the Proteobacteria, followed by the Planctomycetes. 14 OTUs were shared by all bioreactors, but none of them belonged to the Brocadiales order. Statistical analysis at OTU level showed that differences in the microbial communities were high, and that the main driver of the bacterial assemblage composition was different for the distinct phyla identified in the six bioreactors, depending on bioreactor technology or influent wastewater characteristics. PMID- 26260062 TI - Bub1/BubR1: swiss army knives at kinetochores. PMID- 26260061 TI - Prazosin + Naltrexone Decreases Alcohol Drinking More Effectively Than Does Either Drug Alone in P Rats with a Protracted History of Extensive Voluntary Alcohol Drinking, Dependence, and Multiple Withdrawals. AB - BACKGROUND: Prazosin (PRZ; an alpha1 -adrenergic receptor antagonist) and naltrexone (NTX; a nonspecific opioid receptor antagonist) each decrease alcohol drinking when administered to rats selectively bred for high voluntary alcohol drinking (alcohol-preferring or "P"), and the combination of PRZ + NTX decreases alcohol drinking more effectively than does either drug alone. As drug responsiveness can depend on history of alcohol drinking and dependence, we investigated whether various schedules of PRZ and NTX administration, alone or in combination, are effective in decreasing alcohol drinking in male P rats with a history of protracted voluntary alcohol drinking, dependence, and repeated withdrawals closely resembling human alcoholism. METHODS: Male P rats became alcohol-dependent during 1 year of ad libitum 24 h/d access to food, water, and 20% alcohol with repetitive temporary alcohol withdrawals. Four sequential studies then addressed effects of oral PRZ (2 mg/kg) and NTX (10 mg/kg), alone or together, on alcohol drinking during: (i) daily alcohol access with daily drug treatment, (ii) intermittent alcohol access with daily drug treatment, (iii) intermittent alcohol access with occasional drug treatment, and (iv) postdeprivation reinstatement of alcohol access. RESULTS: The combination of PRZ + NTX consistently suppressed alcohol drinking during daily or intermittent alcohol access conditions and when drug treatment was either daily or occasional. PRZ + NTX was consistently more effective than either drug alone. The reduction in alcohol drinking was not due to sedation, motor effects, or malaise. CONCLUSIONS: Both daily and "as-needed" treatment with PRZ + NTX are highly effective in suppressing daily, intermittent, and postdeprivation alcohol drinking in male P rats with a protracted history of alcohol dependence and repeated withdrawals. This drug combination may be especially effective for treating individuals with long histories of heavy alcohol abuse, dependence, and repeated relapse, as commonly encountered in clinical practice. PMID- 26260063 TI - Immunohistochemical localisation and effect of matrix metalloproteinases and their inhibitors on canine spontaneous periodontitis. AB - Periodontitis is commonly observed in dogs. In human medicine, it is well documented that matrix metalloproteinases (MMPs) are involved in the destruction of the periodontium. Therefore, the aim of this prospective study was to investigate the impact of MMPs and their inhibitors, the TIMPs (tissue inhibitors of metalloproteinases), on canine periodontitis. The oral cavities of 57 dogs were examined clinically and radiologically. Gingival biopsies were obtained from the examined dogs and histologically analysed via haematoxylin and eosin stained sections. Immunohistological detection of MMP-2, MMP-3, MMP-8 and MMP-9 as well as TIMP-1 and TIMP-2 was performed by the avidin-biotin peroxidase complex technique. All sections were evaluated by light microscopy. Statistically significant positive correlations were detected between the histologically verified degree of inflammation and the expression of MMP-2, MMP-3, MMP-8 and MMP 9 as well as between changes in collagen fibre content and the occurrence of MMP 2, MMP-8 and MMP-9. Concerning TIMP-1 and TIMP-2, non-significant, generally negative correlations were observed. In summary, in canine periodontitis, an increased expression of the above mentioned MMPs and a tendentially decreased expression of TIMPs are present. In conclusion, in canine periodontitis, a MMP TIMP imbalance is suggestive of contributing to the destruction of the periodontium. PMID- 26260064 TI - Prevalence of equine coronavirus in nasal secretions from horses with fever and upper respiratory tract infection. PMID- 26260065 TI - Reflections on different governance styles in regulating science: a contribution to 'Responsible Research and Innovation'. AB - In European science and technology policy, various styles have been developed and institutionalised to govern the ethical challenges of science and technology innovations. In this paper, we give an account of the most dominant styles of the past 30 years, particularly in Europe, seeking to show their specific merits and problems. We focus on three styles of governance: a technocratic style, an applied ethics style, and a public participation style. We discuss their merits and deficits, and use this analysis to assess the potential of the recently established governance approach of 'Responsible Research and Innovation' (RRI). Based on this analysis, we reflect on the current shaping of RRI in terms of 'doing governance'. PMID- 26260066 TI - ConnectViz: Accelerated Approach for Brain Structural Connectivity Using Delaunay Triangulation. AB - Stroke is a cardiovascular disease with high mortality and long-term disability in the world. Normal functioning of the brain is dependent on the adequate supply of oxygen and nutrients to the brain complex network through the blood vessels. Stroke, occasionally a hemorrhagic stroke, ischemia or other blood vessel dysfunctions can affect patients during a cerebrovascular incident. Structurally, the left and the right carotid arteries, and the right and the left vertebral arteries are responsible for supplying blood to the brain, scalp and the face. However, a number of impairment in the function of the frontal lobes may occur as a result of any decrease in the flow of the blood through one of the internal carotid arteries. Such impairment commonly results in numbness, weakness or paralysis. Recently, the concepts of brain's wiring representation, the connectome, was introduced. However, construction and visualization of such brain network requires tremendous computation. Consequently, previously proposed approaches have been identified with common problems of high memory consumption and slow execution. Furthermore, interactivity in the previously proposed frameworks for brain network is also an outstanding issue. This study proposes an accelerated approach for brain connectomic visualization based on graph theory paradigm using compute unified device architecture, extending the previously proposed SurLens Visualization and computer aided hepatocellular carcinoma frameworks. The accelerated brain structural connectivity framework was evaluated with stripped brain datasets from the Department of Surgery, University of North Carolina, Chapel Hill, USA. Significantly, our proposed framework is able to generate and extract points and edges of datasets, displays nodes and edges in the datasets in form of a network and clearly maps data volume to the corresponding brain surface. Moreover, with the framework, surfaces of the dataset were simultaneously displayed with the nodes and the edges. The framework is very efficient in providing greater interactivity as a way of representing the nodes and the edges intuitively, all achieved at a considerably interactive speed for instantaneous mapping of the datasets' features. Uniquely, the connectomic algorithm performed remarkably fast with normal hardware requirement specifications. PMID- 26260067 TI - A Quantitative Measure of Conformational Changes in Apo, Holo and Ligand-Bound Forms of Enzymes. AB - Determination of the native geometry of the enzymes and ligand complexes is a key step in the process of structure-based drug designing. Enzymes and ligands show flexibility in structural behavior as they come in contact with each other. When ligand binds with active site of the enzyme, in the presence of cofactor some structural changes are expected to occur in the active site. Motivation behind this study is to determine the nature of conformational changes as well as regions where such changes are more pronounced. To measure the structural changes due to cofactor and ligand complex, enzyme in apo, holo and ligand-bound forms is selected. Enzyme data set was retrieved from protein data bank. Fifteen triplet groups were selected for the analysis of structural changes based on selection criteria. Structural features for selected enzymes were compared at the global as well as local region. Accessible surface area for the enzymes in entire triplet set was calculated, which describes the change in accessible surface area upon binding of cofactor and ligand with the enzyme. It was observed that some structural changes take place during binding of ligand in the presence of cofactor. This study will helps in understanding the level of flexibility in protein-ligand interaction for computer-aided drug designing. PMID- 26260068 TI - Predictors for 1-year mortality following hip fracture: a retrospective review of 465 consecutive patients. AB - INTRODUCTION: In Europe, trauma admissions and in particular hip fractures are on the rise. In recent years, health care systems have placed particular emphasis, including financial incentives, on delivering patients quickly and safely to surgery. At our unit, we have observed that hip fracture patients appear to be at significant risk of mortality even up to a year following injury. This study reviews a consecutive population of hip fracture patients to identify predictors of excess risk. MATERIALS AND METHODS: Four hundred and sixty-five consecutive patients were treated over a 2-year period at our district general hospital with no ward-based orthogeriatricians. Follow-up was for 1 year following hip fracture admission. Statistical analysis of variables and their influence on 1-year mortality were performed by calculating odd's ratio (OR) using a logistic regression model and a p value <0.05 was considered statistically significant. RESULTS: Four patients were lost to follow-up, 18 patients (4.1 %) were managed conservatively, 16 were too unwell for surgery and their mortality rate at 1 year was 50 %. Following hip fracture, we found an overall 1-year mortality rate of 15.1 %. Patients with a time to surgery >=36 h were at significantly increased risk of mortality even up to 1 year. We did not identify a further reduction in mortality in those operated on within 24 h. Raised ORs (p > 0.05) were found with increasing comorbidity, surgery type, independence on discharge, alcohol ingestion, history of smoking, readmission and several biochemical markers. CONCLUSION: Minimising mortality risk, even over the longer term, should begin on admission with prompt optimisation of any acute medical or biochemical abnormalities, followed by early surgery and intensive rehabilitation to maintain patients' functional independence. PMID- 26260069 TI - Health status and return to work in trauma patients at 3 and 6 months post discharge: an Australian major trauma centre study. AB - INTRODUCTION: The aim of this study was to describe post-discharge outcomes, and determine predictors of 3 and 6 months health status outcomes in a population of trauma patients at an inner city major trauma centre. METHODS: This was a prospective cohort study of adult trauma patients admitted to this hospital with 3 and 6 months post-discharge outcomes assessment. Outcome measures were the Physical Component Scores (PCS) and Mental Component Scores (MCS) of the Short Form 12, EQ-5D, and return to work (in any capacity) if working prior to injury. Repeated measures mixed models and generalised estimating equation models were used to determine predictors of outcomes at 3 and 6 months. RESULTS: One hundred and seventy-nine patients were followed up. Patients with lower limb injuries reported lower mean PCS scores between 3 and 6 months (coefficient -4.21, 95 % CI -7.58, -0.85) than those without lower limb injuries. Patients involved in pedestrian incidents or assaults and those with pre-existing mental health diagnoses reported lower mean MCS scores. In adjusted models upper limb injuries were associated with reduced odds of return to work at 3 and 6 months (OR 0.20, 95 % CI 0.07, 0.57) compared to those without upper limb injuries. DISCUSSION: Predictors of poorer physical health status were lower limb injuries and predictors of mental health were related to the mechanism of injury and past mental health. Increasing injury severity score and upper limb injuries were the only predictors of reduced return to work. The results provide insights into the feasibility of routine post-discharge follow-up at a trauma service level. PMID- 26260070 TI - Enhancement of electroactive beta phase crystallization and dielectric constant of PVDF by incorporating GeO2 and SiO2 nanoparticles. AB - Poly(vinylidene fluoride) (PVDF) nanocomposites are recently gaining importance due to their unique dielectric and electroactive responses. In this study, GeO2 nanoparticles/PVDF and SiO2 nanoparticles/PVDF nanocomposite films were prepared by a simple solution casting technique. The surface morphology and structural properties of the as-prepared films were studied by X-ray diffraction, scanning electron microscopy, and FT-IR spectroscopy techniques. The studies reveal that the incorporation of GeO2 or SiO2 nanoparticles leads to an enhancement in the electroactive beta phase fraction of PVDF due to the strong interactions between the negatively charged nanoparticle surface and polymer. Analysis of the thermal properties of the as-prepared samples also supports the increment of the beta phase fraction in PVDF. Variation of dielectric constant, dielectric loss, and ac conductivity with frequency and loading fraction of the nanoparticles were also studied for all the as-prepared films. Dielectric constant of the nanocomposite films increases with increasing nanofiller concentration in PVDF. 15 mass% SiO2 loaded PVDF film shows the highest dielectric constant, which can be attributed to the smaller size of SiO2 nanoparticles and the homogeneous and discrete dispersion of SiO2 nanoparticles in PVDF matrix. PMID- 26260071 TI - Might your respiratory patient have alpha-1 antitrypsin deficiency? PMID- 26260072 TI - Thymoquinone ameliorates testicular tissue inflammation induced by chronic administration of oral sodium nitrite. AB - Although sodium nitrite has been widely used as food preservative, building bases of scientific evidence about nitrite continues to oppose the general safety in human health. Moreover, thymoquinone (TQ) has therapeutic potential as antioxidant, anti-inflammatory, antibacterial and anticancer. Therefore, we investigated the effects of both sodium nitrite and TQ on testicular tissues of rats. Forty adult male Sprague Dawley rats were used. They received either 80 mg kg(-1) sodium nitrite or 50 mg kg(-1) TQ daily for twelve weeks. Serum testosterone was measured. Testis were weighed and the testicular tissue homogenates were used for measurements of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-4, IL-6, IL10, caspase-3, caspase-8 and caspase-9. Sodium nitrite resulted in significant reduction in serum testosterone concentration and elevation in testis weight and Gonado-Somatic Index. We found significant reduction in testicular tissues levels of IL-4 and IL-10 associated with elevated levels of TNF-alpha, IL-1beta, IL-6, caspase-3, caspase-8 and caspase-9. In conclusion, chronic oral sodium nitrite induced changes in the weight of rat testis accompanied by elevation in the testicular tissue level of oxidative stress markers and inflammatory cytokines. TQ attenuated sodium nitrite induced testicular tissue damage through blocking oxidative stress, restoration of normal inflammatory cytokines balance and blocking of apoptosis. PMID- 26260073 TI - Energy-dense fast food products cost less: an observational study of the energy density and energy cost of Australian fast foods. AB - OBJECTIVE: To examine the association between energy cost and energy density of fast food products. METHODS: Twenty Sydney outlets of the five largest fast food chains were surveyed four times. Price and kilojoule data were collected for all limited-time-only menu items (n=54) and a sample of standard items (n=67). Energy cost ($/kilojoule) and energy density (kilojoules/gram) of menu items were calculated. RESULTS: There was a significant inverse relationship between menu item energy density and energy cost (p<0.001). Salads had the highest energy cost, while value items, meals that included a dessert and family meals had the lowest. CONCLUSIONS: Fast food chains could provide a wider range of affordable, lower-energy foods, use proportional pricing of larger serve sizes, or change defaults in meals to healthier options. More research is required to determine the most effective strategy to reduce the negative impact of fast food on the population's diet. IMPLICATIONS: Current pricing in the fast food environment may encourage unhealthier purchases. PMID- 26260074 TI - Regulation of the Ca(2+)-ATPase by cholesterol: a specific or non-specific effect? AB - Like other integral membrane proteins, the activity of the Sarco/Endoplasmic Reticulum Ca(2+)-ATPase (SERCA) is regulated by the membrane environment. Cholesterol is present in the endoplasmic reticulum membrane at low levels, and it has the potential to affect SERCA activity both through direct, specific interaction with the protein or through indirect interaction through changes of the overall membrane properties. There are experimental data arguing for both modes of action for a cholesterol-mediated regulation of SERCA. In the current study, coarse-grained molecular dynamics simulations are used to address how a mixed lipid-cholesterol membrane interacts with SERCA. Candidates for direct regulatory sites with specific cholesterol binding modes are extracted from the simulations. The binding pocket for thapsigargin, a nanomolar inhibitor of SERCA, has been suggested as a cholesterol binding site. However, the thapsigargin binding pocket displayed very little cholesterol occupation in the simulations. Neither did atomistic simulations of cholesterol in the thapsigargin binding pocket support any specific interaction. The current study points to a non specific effect of cholesterol on SERCA activity, and offers an alternative interpretation of the experimental results used to argue for a specific effect. PMID- 26260075 TI - On the influence of marrow on the mechanical behavior of porcine trabecular bone under dynamic loading: a numerical investigation. PMID- 26260076 TI - Key features and clinical variability of COG6-CDG. AB - The conserved oligomeric Golgi (COG) complex consists of eight subunits and plays a crucial role in Golgi trafficking and positioning of glycosylation enzymes. Mutations in all COG subunits, except subunit 3, have been detected in patients with congenital disorders of glycosylation (CDG) of variable severity. So far, 3 families with a total of 10 individuals with biallelic COG6 mutations have been described, showing a broad clinical spectrum. Here we present 7 additional patients with 4 novel COG6 mutations. In spite of clinical variability, we delineate the core features of COG6-CDG i.e. liver involvement (9/10), microcephaly (8/10), developmental disability (8/10), recurrent infections (7/10), early lethality (6/10), and hypohidrosis predisposing for hyperthermia (6/10) and hyperkeratosis (4/10) as ectodermal signs. Regarding all COG6-related disorders a genotype-phenotype correlation can be discerned ranging from deep intronic mutations found in Shaheen syndrome as the mildest form to loss-of function mutations leading to early lethal CDG phenotypes. A comparison with other COG deficiencies suggests ectodermal changes to be a hallmark of COG6 related disorders. Our findings aid clinical differentiation of this complex group of disorders and imply subtle functional differences between the COG complex subunits. PMID- 26260077 TI - Safety of laronidase delivered into the spinal canal for treatment of cervical stenosis in mucopolysaccharidosis I. AB - Enzyme replacement therapy with laronidase (recombinant human alpha-l iduronidase) is successfully used to treat patients with mucopolysaccharidosis type I (MPS I). However, the intravenously-administered enzyme is not expected to treat or prevent neurological deterioration. As MPS I patients suffer from spinal cord compression due in part to thickened spinal meninges, we undertook a phase I clinical trial of lumbar intrathecal laronidase in MPS I subjects age 8 years and older with symptomatic (primarily cervical) spinal cord compression. The study faced significant challenges, including a heterogeneous patient population, difficulty recruiting subjects despite an international collaborative effort, and an inability to include a placebo-controlled design due to ethical concerns. Nine serious adverse events occurred in the subjects. All subjects reported improvement in symptomatology and showed improved neurological examinations, but objective outcome measures did not demonstrate change. Despite limitations, we demonstrated the safety of this approach to treating neurological disease due to MPS I. PMID- 26260079 TI - Breakdown of the striatal-default mode network loop in schizophrenia. AB - The striatum has been shown to be a core region in schizophrenia with functional and structural deficits. Previous studies have confirmed the schizophrenia related functional connectivity between the striatal and cortical regions. However, among these, few studies have attempted to determine the directional flow of the influence. In the present study, we used resting-state fMRI to explore the directed connectivity between the striatum and the cortical regions in schizophrenia. Employing a Granger causality analysis, we observed a significant failure of the directed inhibitory influence of the striatum on the default mode network (DMN) in schizophrenia. Furthermore, the reciprocal influence of the DMN on the striatum was also significantly reduced. These findings provide compelling evidence for a breakdown of the striatum-DMN loop in schizophrenia. This abnormal connectivity could be related to clinical variables. In conclusion, our study suggests that abnormally directed influences between the striatum and the DMN might be a biomarker of schizophrenia and also reveals a potential target for treatment. PMID- 26260078 TI - Molecular evidence for decreased synaptic efficacy in the postmortem olfactory bulb of individuals with schizophrenia. AB - Multiple lines of evidence suggest altered synaptic plasticity/connectivity as a pathophysiologic mechanism for various symptom domains of schizophrenia. Olfactory dysfunction, an endophenotype of schizophrenia, reflects altered activity of the olfactory circuitry, which conveys signals from olfactory receptor neurons to the olfactory cortex via synaptic connections in the glomeruli of the olfactory bulb. The olfactory system begins with intranasal olfactory receptor neuron axons synapsing with mitral and tufted cells in the glomeruli of the olfactory bulb, which then convey signals directly to the olfactory cortex. We hypothesized that olfactory dysfunction in schizophrenia is associated with dysregulation of synaptic efficacy in the glomeruli of the olfactory bulb. To test this, we employed semi-quantitative immunohistochemistry to examine the olfactory bulbs of 13 postmortem samples from schizophrenia and their matched control pairs for glomerular expression of 5 pre- and postsynaptic proteins that are involved in the integrity and function of synapses. In the glomeruli of schizophrenia cases compared to their matched controls, we found significant decreases in three presynaptic proteins which play crucial roles in vesicular glutamate transport - synapsin IIa (-18.05%, p=0.019), synaptophysin ( 24.08% p=0.0016) and SNAP-25 (-23.9%, p=0.046). Two postsynaptic proteins important for spine formation and glutamatergic signaling were also decreased spinophilin (-17.40%, p=0.042) and PSD-95 (-34.06%, p=0.015). These findings provide molecular evidence for decreased efficacy of synapses within the olfactory bulb, which may represent a synaptic mechanism underlying olfactory dysfunction in schizophrenia. PMID- 26260080 TI - The factor structure and clinical utility of formal thought disorder in first episode psychosis. AB - BACKGROUND: Formal thought disorder (FTD) is a core feature of psychosis, however there are gaps in our knowledge about its prevalence and factor structure. We had two aims: first, to establish the factor structure of FTD; second, to explore the clinical utility of dimensions of FTD in order to further the understanding of its nosology. METHODS: A cross-validation study was undertaken to establish the factor structure of FTD in first episode psychosis (FEP). The relative utility of FTD categories vs. dimensions across diagnostic categories was investigated. RESULTS: The prevalence of clinically significant FTD in this FEP sample was 21%, although 41% showed evidence of disorganised speech, 20% displayed verbosity and 24% displayed impoverished speech. A 3-factor model was identified as the best fit for FTD, with disorganisation, poverty and verbosity dimensions (GFI=0.99, RMR=0.07). These dimensions of FTD accurately distinguished affective from non affective diagnostic categories. A categorical approach to FTD assessment was useful in identifying markers of clinical acuteness, as identified by short duration of untreated psychosis (OR=2.94, P<0.01) and inpatient treatment status (OR=3.98, P<0.01). CONCLUSION: FTD is moderately prevalent and multi-dimensional in FEP. Employing both a dimensional and categorical assessment of FTD gives valuable clinical information, however there may be a need to revise our conceptualisation of the nosology of FTD. The prognostic value of FTD, as well as its neural basis, requires elucidation. PMID- 26260081 TI - Neurocognitive and social cognitive predictors of cannabis use in first-episode psychosis. AB - BACKGROUND: Findings are unclear as to whether cannabis use is associated with better cognitive functioning in individuals with psychosis. OBJECTIVES: To elucidate the association between cannabis use, neurocognition and social cognition in first-episode psychosis (FEP). METHODS: Secondary data analysis was conducted on data from 133 FEP participants who had enrolled in a randomized controlled trial of a vocational intervention. Participants completed a neurocognitive and social cognitive battery and characteristics of cannabis use were documented (disorder, recency, frequency and dose). Principal axis factor analysis was used to determine the underlying structure of the cognitive batteries. Regression techniques were used to examine cognitive predictors of current cannabis use disorder (CUD), and recency and frequency of cannabis use. Bivariate correlations were used to examine associations between cognition and dose of cannabis consumption. RESULTS: Male gender (p=.037) was the only significant predictor of having a current CUD. Better processing speed (p=.022) and social cognition (p=.039), male gender (p<.001), and fewer negative symptoms (p=.036) predicted recency of cannabis use. Faster processing speed (p=.007) and male gender (p=.006) also predicted frequency of cannabis use. No variables were significantly associated with dose of cannabis consumption. CONCLUSIONS: Better social cognition and processing speed abilities predicting recency and frequency of cannabis use are consistent with cannabis users having higher cognitive abilities. A positive relationship between cannabis use and cognition may be the result of more drug taking opportunities in less cognitively impaired individuals with psychosis. PMID- 26260083 TI - SUPPORTING MORE RELIABLE RESULTS. AB - Studies are finding that many groundbreaking published results with implications for human health and disease cannot be replicated. Sarah Webb explores how reproducibility issues in basic science are creating bumps on the road to the clinic. PMID- 26260082 TI - Bioavailability of insulin detemir and human insulin at the level of peripheral interstitial fluid in humans, assessed by open-flow microperfusion. AB - AIMS: To find an explanation for the lower potency of insulin detemir observed in humans compared with unmodified human insulin by investigating insulin detemir and human insulin concentrations directly at the level of peripheral insulin sensitive tissues in humans in vivo. METHODS: Euglycaemic-hyperinsulinaemic clamp experiments were performed in healthy volunteers. Human insulin was administered i.v. at 6 pmol/kg/min and insulin detemir at 60 pmol/kg/min, achieving a comparable steady-state pharmacodynamic action. In addition, insulin detemir was doubled to 120 pmol/kg/min. Minimally invasive open-flow microperfusion (OFM) sampling methodology was combined with inulin calibration to quantify human insulin and insulin detemir in the interstitial fluid (ISF) of subcutaneous adipose and skeletal muscle tissue. RESULTS: The human insulin concentration in the ISF was ~115 pmol/l or ~30% of the serum concentration, whereas the insulin detemir concentration in the ISF was ~680 pmol/l or ~2% of the serum concentration. The molar insulin detemir interstitial concentration was five to six times higher than the human insulin interstitial concentration and metabolic clearance of insulin detemir from serum was substantially reduced compared with human insulin. CONCLUSIONS: OFM proved useful for target tissue measurements of human insulin and the analogue insulin detemir. Our tissue data confirm a highly effective retention of insulin detemir in the vascular compartment. The higher insulin detemir relative to human insulin tissue concentrations at comparable pharmacodynamics, however, indicate that the lower potency of insulin detemir in humans is attributable to a reduced effect in peripheral insulin-sensitive tissues and is consistent with the reduced in vitro receptor affinity. PMID- 26260084 TI - Improved split-ubiquitin screening technique to identify surface membrane protein protein interactions. AB - Yeast-based methods are still the workhorse for the detection of protein-protein interactions (PPIs) in vivo. Yeast two-hybrid (Y2H) systems, however, are limited to screening for a specific group of molecules that interact in a particular cell compartment. For this reason, the split-ubiquitin system (SUS) was developed to allow screening of cDNA libraries of full-length membrane proteins for protein protein interactions in Saccharomyces cerevisiae. Here we demonstrate that a modification of the widely used membrane SUS involving the transmembrane (TM) domain of the yeast receptor Wsc1 increases the stringency of screening and improves the selectivity for proteins localized in the plasma membrane (PM). PMID- 26260085 TI - A novel tool for stable genomic reporter gene integration to analyze heterogeneity in Photorhabdus luminescens at the single-cell level. AB - Determination of reporter gene activity at the single-cell level is a prerequisite for analyzing heterogeneous gene expression in bacteria. The insect pathogenic enteric bacterium Photorhabdus luminescens is an excellent organism in which to study heterogeneity since it exists in two phenotypically different forms, called the primary and secondary variant. A tool for generating stable genomic integrations of reporter genes has been lacking for these bacteria, and this has hampered the acquisition of reliable data sets for promoter activities at the single-cell level. We therefore generated a plasmid tool named pPINT mCherry for the easy and stable introduction of gene fragments upstream of an mCherry reporter gene followed by stable integration of the plasmid into the P. luminescens genome at the rpmE/glmS intergenic region. We demonstrate that the genomic integration of reporter genes for single-cell analysis is necessary in P. luminescens since plasmid-borne reporter genes mimic heterogeneity and are therefore not applicable in these bacteria, in contrast to their use in single cell analysis in other bacteria like Escherichia coli. PMID- 26260086 TI - Traxtile: Interactive editing of cell tracks in time-lapse images. AB - Time-lapse imaging can be used to quantify how cells move, divide, and die over time and under defined culture conditions. Open source software packages such as CellProfiler, Icy, and Fiji provide robust and convenient interfaces for performing such analyses. However, object tracking algorithms are imperfect, and validation of significant events is often required. This is challenging, as CellProfiler produces only tabular data for object tracking, and the graphical tools in Icy and Fiji are not optimal for manual review of these events. Here we describe Traxtile, a program that allows interactive graphical review and revision of object tracking assignments. Traxtile imports initial assignments and automatically identifies events needing review (i.e., apparent creation of new objects, splits, merges, and losses). For each such event, the object track is displayed on a montage of images centered on the event and spanning the preceding and subsequent frames. Links between cells in successive frames can be reviewed and edited, yielding validated tracks for the image series. Reports summarize events from the validated tracks. Traxtile is implemented in Python version 2.7 using standard distribution libraries (available at www.python.org) and is freely available at https://github.com/braunb/traxtile-public. PMID- 26260087 TI - Reducing microbial and human contamination in DNA extractions from ancient bones and teeth. AB - Although great progress has been made in improving methods for generating DNA sequences from ancient biological samples, many, if not most, samples are still not amenable for analyses due to overwhelming contamination with microbial or modern human DNA. Here we explore different DNA decontamination procedures for ancient bones and teeth for use prior to DNA library preparation and high throughput sequencing. Two procedures showed promising results: (i) the release of surface-bound DNA by phosphate buffer and (ii) the removal of DNA contamination by sodium hypochlorite treatment. Exposure to phosphate removes on average 64% of the microbial DNA from bone powder but only 37% of the endogenous DNA (from the organism under study), increasing the percentage of informative sequences by a factor of two on average. An average 4.6-fold increase, in one case reaching 24-fold, is achieved by sodium hypochlorite treatment, albeit at the expense of destroying 63% of the endogenous DNA preserved in the bone. While both pretreatment methods described here greatly reduce the cost of genome sequencing from ancient material due to efficient depletion of microbial DNA, we find that the removal of human DNA contamination remains a challenging problem. PMID- 26260088 TI - Isolation of segmented filamentous bacteria from complex gut microbiota. AB - Segmented filamentous bacteria (SFB) modulate the ontogeny of the immune system, and their presence can significantly affect mouse models of disease. Until recently, the inability to successfully culture SFB has made controlled studies on the mechanisms by which these bacteria exert their influence problematic. Here, we report a new method for selecting SFB from complex microbial mixtures, providing researchers a simple and cost-effective means to prepare pure infective inocula for prospective studies and also to compare individual SFB isolates. PMID- 26260089 TI - Automated measurement of ommatidia in the compound eyes of beetles. AB - The size of the ommatidia that compose the insect compound eye is linked to visual capacity, physiological performance, and cell size. Therefore, rapid and reliable methods for measuring ommatidia can advance research on insect ecology and evolution. We developed an automated method to measure ommatidia in nail polish imprints of the eyes of three Carabidae beetle species using the widely available, free software ImageJ. Our automated method was equivalent to a traditional manual method in terms of accuracy but had the advantage of being 70 times faster. We provide access to our algorithm, which can be used to investigate biological phenomena ranging from the functional architecture of the compound eye to the cellular basis of the evolution of body size and metabolic rates. PMID- 26260090 TI - Gentian violet inhibits MDA-MB-231 human breast cancer cell proliferation, and reverses the stimulation of osteoclastogenesis and suppression of osteoblast activity induced by cancer cells. AB - Gentian violet (GV) is a cationic triphenylmethane dye, with potent antifungal and antibacterial activity. We recently reported that in vitro GV suppresses the differentiation of bone resorbing osteoclasts while stimulating the differentiation and activity of bone forming osteoblasts. Breast cancer is highly metastatic to bone and drives bone turnover that further promotes cancer engraftment and expansion, the so-called vicious cycle. In humans, breast cancer metastases cause osteolytic lesions and skeletal damage that leads to bone fractures, an additional source of patient morbidity. The MDA-MB-231 human breast cancer cell line is a commonly used model of human breast cancer that when injected into mice metastasizes to bone causing osteolytic lesions by promoting osteoclastic bone resorption and/or suppressing osteoblastic bone formation. In the present study, we investigated the direct action of GV on MDA-MB-231 proliferation, and the capacity of GV to reverse the negative impact of MDA-MB 231 cells on osteoclast and osteoblast differentiation. Our data reveal for the first time that GV suppresses proliferation, and induces apoptosis, of MDA-MB-231 cells. We further demonstrated the capacity of GV to reverse the pro osteoclastogenic and anti-osteoblastic activities of MDA-MB-231 cells in vitro. These data suggest that GV has important applications in the treatment of breast cancer through multiple actions including direct suppression of cancer cell proliferation, breaking the vicious cycle between cancer and bone, and alleviating the skeletal defects induced by bone metastasis. PMID- 26260091 TI - Characterization of acute-on-chronic liver failure and prediction of mortality in Asian patients with active alcoholism. AB - BACKGROUND AND AIMS: Alcoholic liver diseases often evolve to acute-on-chronic liver failure (ACLF), which increases the risk of (multi-)organ failure and death. We investigated the development and characteristics of alcohol-related ACLF and evaluated prognostic scores for prediction of mortality in Asian patients with active alcoholism. METHODS: A total of 205 patients who were hospitalized with severe alcoholic liver disease were included in this retrospective cohort study, after excluding those with serious cardiovascular diseases, malignancy, or co-existing viral hepatitis. The Chronic Liver Failure (CLIF) Consortium Organ Failure score was used in the diagnosis and grading of ACLF, and the CLIF Consortium ACLF score (CLIF-C ACLFs) was used to predict mortality. RESULTS: Patients with ACLF had higher Maddrey discriminant function, model for end-stage liver disease (MELD), and MELD-sodium scores than those without ACLF. Infections were more frequently documented in patients with ACLF (33.3% vs 53.0%; P = 0.004). Predictive factors for ACLF development were systemic inflammatory response syndrome (odds ratio [OR], 2.239; P < 0.001), serum sodium level (OR, 0.939; P = 0.029), and neutrophil count (OR, 1.000; P = 0.021). For prediction of mortality at predefined time points (28-day and 90-day) in patients with ACLF, areas under the receiver-operating characteristic were significantly greater for the CLIF-C ACLFs than for Child-Pugh, MELD, and MELD sodium scores. CONCLUSIONS: Infection and systemic inflammatory response syndrome play an important role in the development of alcohol-related ACLF in Asian patients with active alcoholism. The CLIF-C ACLFs may be more useful for predicting mortality in ACLF cases than liver-specific scoring systems. PMID- 26260092 TI - Safety of Magnetic Resonance Imaging After Implantation of Stainless Steel Embolization Coils. AB - Stainless steel embolization coils (SSEC) have been used for over four decades for vascular occlusion. Recently, the safety of these coils in a magnetic resonance environment has been called into question, with important ramifications for thousands of patients with existing coils in place. We performed a retrospective chart review at five tertiary care pediatric centers evaluating all children and young adults with implanted SSEC who underwent magnetic resonance imaging (MRI). Data reviewed included demographics, coil implantation, MRI studies, and follow-up evaluations. Complications such as heating, discomfort, or device migration were specifically sought. Two hundred and ninety-seven patients with implanted SSEC underwent 539 MRI examinations. The median age at SSEC implantation was 2.3 years (1 week-23.2 years). The MRI studies were performed a median of 7.4 years (4 days-23.1 years) after implantation. No patients experienced any reported complications associated with their MRI examinations during the study or at median follow-up post-MRI of 4.8 years (1 day-23 years). In this large, retrospective review of patients with implanted SSEC undergoing MRI, there were no reported adverse events. These findings support the recent change by Cook Medical Inc. of their standard embolization coils from a designation of magnetic resonance unsafe to conditional. PMID- 26260093 TI - Risk Factors for Interstage Mortality Following the Norwood Procedure: Impact of Sociodemographic Factors. AB - Interstage mortality remains significant for patients undergoing staged palliation for hypoplastic left heart syndrome and other related single right ventricle malformations (HLV). The purpose of this study was to identify factors related to demographics, socioeconomic position, and perioperative course associated with post-Norwood hospital discharge, pre-stage 2, interstage mortality (ISM). Medical record review was conducted for patients with HLV, born from 1/2000 to 7/2009 and discharged alive following the Norwood procedure. Sociodemographic and perioperative factors were reviewed. Patients were determined to have ISM if they died between Norwood procedure hospital discharge and stage 2 palliation. Univariable and multivariable logistic regressions were performed to identify risk factors associated with ISM. A total of 273 patients were included in the analysis; ISM occurred in 32 patients (12%). Multivariable analysis demonstrated that independent risk factors for interstage mortality included teen mothers [adjusted odds ratio (AOR) 6.6, 95% confidence interval (CI) 1.9-22.5], single adult caregivers (AOR 4.1, 95% CI 1.2-14.4), postoperative dysrhythmia (AOR 2.7, 95% CI 1.1-6.4), and longer ICU stay (AOR 2.7, 95% CI 1.2 6.1). Anatomic and surgical course variables were not associated with ISM in multivariable analysis. Patients with HLV are at increased risk of ISM if born to a teen mother, if they lived in a home with only one adult caregiver, suffered a postoperative dysrhythmia, or experienced a prolonged ICU stay. These risk factors are identifiable, and thus these infants may be targeted for interventions to reduce ISM. PMID- 26260094 TI - Left Ventricular Mechanical Property Changes During Acute AV Synchronous Right Ventricular Pacing in Children. AB - Prolonged RV pacing is recognized as a cause of LV dysfunction due to dyssynchronous activation. There are no specific longitudinal parameters known to help predict RV pacing-induced LV dysfunction. The aim of the study was to assess the acute effects of AV synchronous RV pacing on LV mechanics using echocardiographic speckle tracking. Nineteen children, aged 6-23 years, underwent echocardiographic evaluation prior to and following elective electrophysiology and ablation studies. The subjects were evaluated in sinus rhythm and later with AV synchronous RV pacing at a cycle length of 550 ms with a short AV delay of 80 ms. The echocardiographic clips were analyzed using speckle tracking methods to calculate LV circumferential and longitudinal strain, rotation and twist in all conditions. Acute RV apical pacing decreased LV longitudinal strain from 16.1 +/- 3.7% in sinus rhythm to 14.4 +/- 3.3% (p = 0.03) and LV base rotation from -8.4 degrees +/- 3.6 degrees to -6.4 degrees +/- 4.0 degrees (p = 0.04). The circumferential strain, apical rotation and LV twist were not affected. Separate analysis of subjects with no prior preexcitation showed that acute RV pacing caused significant twist reduction, from 15.9 degrees +/- 7.6 degrees to 12.1 degrees +/- 7.0 degrees (p = 0.02), and decreased longitudinal strain and base rotation. Patients with preexcitation had abnormalities that persisted acutely after ablation. Acute RV apical pacing causes reductions in LV base rotation, longitudinal strain and twist. The recognition of abnormal LV activation patterns may provide longitudinal clues to LV dysfunction in chronically paced patients and potential novel indices of effective CRT interventions to reverse these abnormalities. PMID- 26260095 TI - Long-Term Prostaglandin E1 Infusion for Newborns with Critical Congenital Heart Disease. AB - Prostaglandin E1 is crucial for keeping the patent ductus arteriosus in critical congenital heart disease for the survival and palliation of particularly prematurely born babies until a cardiosurgical intervention is available. In this study, the side effects of prostaglandin E1 in newborns with critical congenital heart disease and clinical outcomes were evaluated. Thirty-five newborns diagnosed with critical congenital heart disease were treated with prostaglandin E1 between January 2012 and September 2014 at our hospital. Patient charts were examined for prostaglandin E1 side effects (metabolic, gastric outlet obstruction, apnea), clinical status, and prognosis. Acquired data were analyzed in the SPSS 20.0 program. Patients with birth weight under 2500 g needed more days of prostaglandin E1 infusion than ones with birthweight over 2500 g (P = 0.016). The ratio of patients with birth weight under 2500 g who received prostaglandin E1 longer than 7 days was higher than the patients with birth weight over 2500 g (P = 0.02). Eighteen side effects were encountered in 11 of 35 patients (31%). Of these side effects, 1 patient had 4, 4 patients had 2, and 6 patients had only 1 side effect. Discontinuation of the therapy was never needed. Prostaglandin E1 is an accepted therapy modality for survival and outcome in critical congenital heart disease in particularly low-birth-weight babies until a surgical intervention is available. Side effects are not less encountered but are almost always manageable, and discontinuation is not needed. PMID- 26260096 TI - Metamorphosis of human lumbar vertebrae induced by VEPTR growth modulation and stress shielding. AB - INTRODUCTION: Distraction-based spinal growth modulation by growing rods or vertical expandable prosthetic titanium ribs (VEPTRs) is the mainstay of instrumented operative strategies to correct early onset spinal deformities. In order to objectify the benefits, it has become common sense to measure the gain in spine height by assessing T1-S1 distance on anteroposterior (AP) radiographs. However, by ignoring growth changes on vertebral levels and by limiting measurement to one plane, valuable data is missed regarding the three-dimensional (3D) effects of growth modulation. This information might be interesting when it comes to final fusion or, even more so, when the protective growing implants are removed and the spine re-exposed to physiologic forces at the end of growth. METHODS: The goal of this retrospective radiographic study was to assess the growth modulating impact of year-long, distraction-based VEPTR treatment on the morphology of single vertebral bodies. We digitally measured lumbar vertebral body height (VBH) and upper endplate depth (VBD) at the time of the index procedure and at follow-up in nine patients with rib-to-ileum constructs (G1) spanning an anatomically normal lumbar spine. Nine patients with congenital thoracic scoliosis and VEPTR rib-to-rib constructs, but uninstrumented lumbar spines, served as controls (G2). All had undergone more than eight half-yearly VEPTR expansions. A Wilcoxon signed-rank test was used for statistical comparison of initial and follow-up VBH, VBD and height/depth (H/D) ratio (significance level 0.05). RESULTS: The average age was 7.1 years (G1) and 5.2 year (G2, p > 0.05) at initial surgery; the average overall follow-up time was 5.5 years (p = 1). In both groups, VBH increased significantly without a significant intergroup difference. Group 1 did not show significant growth in depth, whereas VBD increased significantly in the control group. As a consequence, the H/D ratio increased significantly in group 1 whereas it remained unchanged in group 2. The growth rate for height in mm/year was 1.4 (group 1) and 1.1 (group 2, p = 0.45), and for depth, it was -0.3 and 1.1 (p < 0.05), respectively. CONCLUSIONS: VEPTR growth modulating treatment alters the geometry of vertebral bodies by increasing the H/D ratio. We hypothesize that the implant-related deprivation from axial loads (stress-shielding) impairs anteroposterior growth. The biomechanical consequence of such slender vertebrae when exposed to unprotected loads in case of definitive VEPTR removal at the end of growth is uncertain. PMID- 26260098 TI - Gambling advocacy: lessons from tobacco, alcohol and junk food. AB - OBJECTIVE: To explore the attitudes and opinions of public health experts in gambling and related unhealthy commodity industries towards the tactics used by the gambling industry to prevent reform and the advocacy responses to these tactics. METHODS: In-depth interviews (30-60 minutes) with a convenience sample of 15 public health experts and stakeholders with a public health approach to gambling (n=10), or other unhealthy commodity industries (food, alcohol, tobacco, n=5). RESULTS: Participants described the influences of political lobbying and donations on public policy, and industry framing of problem gambling as an issue of personal responsibility. Industry funding of, and influence over, academic research was considered to be one of the most effective industry tactics to resist reform. Participants felt there was a need to build stronger coalitions and collaborations between independent academics, and to improve the utilisation of media to more effectively shift perceptions of gambling harm away from the individual and towards the product. CONCLUSIONS AND IMPLICATIONS: Gambling industry tactics are similar to the tactics of other unhealthy commodity industries. However, advocacy initiatives to counter these tactics in gambling are less developed than in other areas. The formation of national public health coalitions, as well as a strong evidence base regarding industry tactics, will help to strengthen advocacy initiatives. PMID- 26260097 TI - From genotypes to phenotypes: expression levels of genes encompassing adaptive SNPs in black spruce. AB - KEY MESSAGE: Measuring transcript levels for adaptive genes revealed polymorphisms having cis -effect upon gene expression levels related to phenotype variation in a black spruce natural population. Trees growing in temperate and boreal regions must acclimate to changes in climatic factors such as low winter temperatures to survive to seasonal variations. Common garden studies have shown that genetic variation in quantitative traits helps species to survive and adapt to environmental changes and local conditions. Twenty-four genes carrying SNPs were previously associated with genetic adaptation in black spruce (Picea mariana [Mill.] BSP). The objectives of this study were to investigate the potential role of these genes in regulation of winter acclimation and adaptation by studying their patterns of expression as a function of the physiological stage during the annual growth cycle, tissue type, and their SNP genotypic class. Considerable variability in gene expression was observed between different vegetative tissues or organs, and between physiological stages. The genes were expressed predominantly in tissues that could be linked more directly to winter acclimation and adaptation. The expression levels of several of the genes were significantly related to variation in tree height growth or budset timing and expression level variation related to SNP genotypic classes was observed in four of the genes. An interaction between genotypic classes and physiological stages was also observed for some genes, indicating genotypes with different reaction norms in terms of gene expression. PMID- 26260099 TI - Role of the Chemical Environment beyond the Coordination Site: Structural Insight into Fe(III) Protoporphyrin Binding to Cysteine-Based Heme-Regulatory Protein Motifs. AB - The importance of heme as a transient regulatory molecule has become a major focus in biochemical research. However, detailed information about the molecular basis of transient heme-protein interactions is still missing. We report an in depth structural analysis of Fe(III) heme-peptide complexes by a combination of UV/Vis, resonance Raman, and 2D-NMR spectroscopic methods. The experiments reveal insights both into the coordination to the central iron ion and into the spatial arrangement of the amino acid sequences interacting with protoporphyrin IX. Cysteine-based peptides display different heme-binding behavior as a result of the existence of ordered, partially ordered, and disordered conformations in the heme-unbound state. Thus, the heme-binding mode is clearly the consequence of the nature and flexibility of the residues surrounding the iron ion coordinating cysteine. Our analysis reveals scenarios for transient binding of heme to heme regulatory motifs in proteins and demonstrates that a thorough structural analysis is required to unravel how heme alters the structure and function of a particular protein. PMID- 26260100 TI - Identifying Patients Suitable for Discharge After a Single-Presentation High Sensitivity Troponin Result: A Comparison of Five Established Risk Scores and Two High-Sensitivity Assays. AB - STUDY OBJECTIVE: We compare the ability of 5 established risk scores to identify patients with suspected acute coronary syndromes who are suitable for discharge after a modified single-presentation high-sensitivity troponin result. METHODS: This was a prospective observational study conducted in a UK district general hospital emergency department. Consecutive adults recruited with suspected acute coronary syndrome for whom attending physicians determined evaluation with serial troponin testing was required. Index tests were definitions of low risk applied to modified Goldman, Thrombolysis in Myocardial Infarction (TIMI), Global Registry of Acute Cardiac Events (GRACE), History, ECG, Age, Risk Factors, Troponin (HEART), and Vancouver Chest Pain Rule risk scores, incorporating either high-sensitivity troponin T or I results. The endpoint was acute myocardial infarction within 30 days. A test sensitivity threshold for acute myocardial infarction of 98% was chosen. Clinical utility was defined as a negative predictive value greater than or equal to 99.5% and identification of greater than 30% suitable for discharge. RESULTS: Nine hundred fifty-nine patients underwent high-sensitivity troponin T analysis and 867 underwent high-sensitivity troponin I analysis. In the high-sensitivity troponin T group, 79 of 959 (8.2%) had an acute myocardial infarction and 66 of 867 (7.6%) in the high-sensitivity troponin I group. Two risk scores (GRACE <80 and HEART <=3) did not have the potential to achieve a sensitivity of 98% with high-sensitivity troponin T, and 3 scores (Goldman <=1, TIMI <=1, and GRACE <80) with high-sensitivity troponin I. A TIMI score of 0 or less than or equal to 1 and modified Goldman score less than or equal to 1 with high-sensitivity troponin T, and TIMI score of 0 and HEART score of less than or equal to 3 with high-sensitivity troponin I had the potential to achieve a negative predictive value greater than or equal to 99.5% while identifying greater than 30% of patients as suitable for immediate discharge. CONCLUSION: With established risk scores, it may be possible to identify greater than 30% of patients suitable for discharge, with a negative predictive value greater than or equal to 99.5% for the diagnosis of acute myocardial infarction, using a single high-sensitivity troponin test result at presentation. There is variation in high-sensitivity troponin assays, which may have implications in introducing rapid rule-out protocols. PMID- 26260102 TI - Limits for density dependent time inhomogeneous Markov processes. AB - A new functional law of large numbers to approximate a time inhomogeneous Markov process that is only density dependent in the limit as an index parameter goes to infinity is developed. This extends previous results by other authors to a broader class of Markov processes while relaxing some of the conditions required for those results to hold. This result is applied to a stochastic metapopulation model that accounts for spatial structure as well as within patch dynamics with the novel addition of time dependent dynamics. The resulting nonautonomous differential equation is analysed to provide conditions for extinction and persistence for a number of examples. This condition shows that the migration of a species will positively impact the reproduction in less populated areas while negatively impacting densely populated areas. PMID- 26260101 TI - Multicenter Analysis of Immune Biomarkers and Heart Transplant Outcomes: Results of the Clinical Trials in Organ Transplantation-05 Study. AB - Identification of biomarkers that assess posttransplant risk is needed to improve long-term outcomes following heart transplantation. The Clinical Trials in Organ Transplantation (CTOT)-05 protocol was an observational, multicenter, cohort study of 200 heart transplant recipients followed for the first posttransplant year. The primary endpoint was a composite of death, graft loss/retransplantation, biopsy-proven acute rejection (BPAR), and cardiac allograft vasculopathy (CAV) as defined by intravascular ultrasound (IVUS). We serially measured anti-HLA- and auto-antibodies, angiogenic proteins, peripheral blood allo-reactivity, and peripheral blood gene expression patterns. We correlated assay results and clinical characteristics with the composite endpoint and its components. The composite endpoint was associated with older donor allografts (p < 0.03) and with recipient anti-HLA antibody (p < 0.04). Recipient CMV-negativity (regardless of donor status) was associated with BPAR (p < 0.001), and increases in plasma vascular endothelial growth factor-C (OR 20; 95%CI:1.9 218) combined with decreases in endothelin-1 (OR 0.14; 95%CI:0.02-0.97) associated with CAV. The remaining biomarkers showed no relationships with the study endpoints. While suboptimal endpoint definitions and lower than anticipated event rates were identified as potential study limitations, the results of this multicenter study do not yet support routine use of the selected assays as noninvasive approaches to detect BPAR and/or CAV following heart transplantation. PMID- 26260104 TI - Application of a new integrated sediment quality assessment method to Huelva estuary and its littoral of influence (Southwestern Spain). AB - A new integrated sediment quality assessment method composed of several assays (particle size profile, total metal content, protease K extraction, total organic carbon, toxicity bioassay with Photobacterium phosphoreum and macrobenthic community alteration) that provides a single result, the environmental degradation index (EDI), has been developed. The new method was tested on the Huelva estuary (southwest of Spain), a highly polluted area where metals dissolved in the water of the Tinto and Odiel rivers precipitate after flowing through the Iberian Pyrite Belt, one of the largest metallogenic areas of massive sulphide deposits in the world. The proposed method satisfactorily was able to reflect different degrees of pollution on the environmental degradation index. Thus, EDI categorized littoral samples as slightly degraded and all the Tinto and some of the Odiel as very highly degraded, emphasizing the lower zone of the Tinto estuary as the most deeply degraded of the entire study area. PMID- 26260103 TI - Functional and homeostatic defects of regulatory T cells in patients with coronary artery disease. AB - OBJECTIVE: Regulatory T cells (Tregs) are considered atheroprotective, and low levels have been associated with the acute coronary syndrome (ACS), particularly non-ST elevation (NSTE)-ACS. However, the functional properties as well as homeostasis of Tregs are mainly unknown in coronary artery disease (CAD). Here, we investigated the composition and functional properties of naive (n) and memory (m)Tregs in patients with NSTE-ACS and in patients 6-12 months post-ACS. METHODS: Based on the expression of CD25, FOXP3, CD127, CD45RA, CD39 and CTLA-4, Treg subsets were defined by flow cytometry in whole blood or isolated CD4(+) T cells. The functional properties of nTregs and mTregs were examined in terms of proliferative capacity and modulation of cytokine secretion. To understand the potential consequences of Treg defects, we also investigated correlations with lipopolysaccharide (LPS)-induced cytokine secretion and ultrasound-defined carotid atherosclerosis. RESULTS: Both NSTE-ACS and post-ACS patients exhibited reduced levels of nTregs (P < 0.001) compared with healthy control subjects, but without compensatory increases in mTregs. Both nTregs and mTregs from patients showed significantly lower replicative rates and impaired capacity to modulate T cell proliferation and secretion of interferon-gamma and IL-10. The Treg defect was also associated with LPS-induced cytokine secretion and increased burden of carotid atherosclerosis. CONCLUSION: Our results demonstrate a functional and homeostatic Treg defect in patients with NSTE-ACS and also in stabilized patients 6-12 months after ACS. Moreover, this defect was associated with a subclinical proinflammatory and atherogenic state. We believe that the failure to preserve Treg function and homeostasis reflects a need for immune-restoring strategies in CAD. PMID- 26260106 TI - Blindness to institutional betrayal by the APA. PMID- 26260105 TI - Prospective study of circulating factor XI and incident venous thromboembolism: The Longitudinal Investigation of Thromboembolism Etiology (LITE). AB - Elevated plasma concentrations of coagulation factor XI may increase risk of venous thromboembolism (VTE), but prospective data are limited. We studied prospectively the associations of plasma factor XI and a key F11 genetic variant with incident VTE in whites and African-Americans. We measured factor XI in 16,299 participants, initially free of VTE, in two prospective population cohorts. We also measured the F11 single nucleotide polymorphism rs4241824, which a genome-wide association study had linked to factor XI concentration. During follow-up, we identified 606 VTEs. The age, race, sex, and study-adjusted hazard ratio of VTE increased across factor XI quintiles (P < 0.001 for trend), and the hazard ratio was 1.51 (95% CI 1.16, 1.97) for the highest versus lowest quintile overall, and was 1.42 (95% CI 1.03, 1.95) in whites and 1.72 (95% CI 1.08, 2.73) in African-Americans. In whites, the F11 variant was associated with both factor XI concentration and VTE incidence (1.15-fold greater incidence of VTE per risk allele). In African-Americans, these associations were absent. In conclusion, this cohort study documented that an elevated plasma factor XI concentration is a risk factor for VTE over extended follow-up, not only in whites but also in African-Americans. In whites, the association of the F11 genetic variant with VTE suggests a causal relation, but we did not observe this genetic relation in African-Americans. PMID- 26260108 TI - A Rare Cause of Chronic Diarrhea Diagnosed by Endoscopic Ultrasound-Guided Fine Needle Aspiration. PMID- 26260107 TI - Prevalence of Barrett's Esophagus in Asian Countries: A Systematic Review and Meta-analysis. AB - BACKGROUND & AIMS: The prevalence and risk factors of Barrett's esophagus (BE) in Asian countries are unclear. Studies report a wide range of BE prevalence in Asian countries. We conducted a systematic review and meta-analysis to examine the prevalence of BE and its temporal changes and risk factors in Asian countries. METHODS: Two investigators performed independent literature searches by using PubMed and EMBASE databases, and subsequent data abstraction for studies had to meet several set inclusion and exclusion criteria. Pooled BE prevalence was calculated by using a random-effect model. Estimates of relative risk for possible risk or protective factors were also calculated. RESULTS: A total of 51 studies (N = 453,147), mainly from Eastern Asia, were included. The pooled prevalence of endoscopic BE was 7.8% (95% confidence interval, 5.0-12.1; 23 studies) and of histologically confirmed BE was 1.3% (95% confidence interval, 0.7-2.2; 28 studies). Most of histologic BE (82.1%) was short-segment BE (<3 cm). There was a trend toward an increase in prevalence of BE over time from 1991 to 2014, especially in Eastern Asian countries. Within BE cohorts, pooled prevalence of low-grade dysplasia, high-grade dysplasia, and esophageal adenocarcinoma was 6.9%, 3.0%, and 2.0%, respectively. Reflux symptoms, male sex, hiatus hernia, and smoking were associated with a significantly increased risk of histologic BE in patients with BE compared with patients without BE. However, half of the patients with histologic BE did not have reflux symptoms. CONCLUSIONS: BE is not uncommon in Asian countries and seems to share similar risk factors and potential for neoplastic progression to those seen in Western countries. PMID- 26260109 TI - Improved Detection of Hepatocellular Carcinoma by Using a Longitudinal Alpha Fetoprotein Screening Algorithm. AB - BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) has limited treatment options when diagnosed at advanced stages; therefore, early detection is critical to reduce mortality. There is disagreement about the value of alpha-fetoprotein (AFP) in HCC surveillance. We aim to improve the sensitivity of AFP in HCC surveillance by using an algorithm that incorporates screening history to define patient-specific thresholds for positive a screen. METHODS: De-identified data from the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial, which enrolled 1050 patients with hepatitis C and advanced fibrosis or cirrhosis who were prospectively followed every 3-6 months, were analyzed. AFP was assayed at each visit, and ultrasonography was performed every 6-12 months. A panel adjudicated the diagnosis of HCC. A parametric empirical Bayes (PEB) screening algorithm, which incorporates screening history, was compared with a single threshold approach for interpreting AFP results. RESULTS: During a median follow-up of 80 months, 88 patients (48 of 427 with cirrhosis and 40 of 621 with advanced fibrosis) were diagnosed with HCC. PEB improved the sensitivity of AFP for detecting all HCC from 60.4% to 77.1% (P < .0005) in patients with cirrhosis and from 72.5% to 87.5% (P = .0015) in patients with advanced fibrosis, when the false-positive rate among all screenings was set at 10%. PEB algorithm detected HCC 1.7-1.9 years earlier in the cirrhosis group and 1.4-1.7 years earlier in the advanced fibrosis group, compared with single threshold approach. CONCLUSIONS: PEB increases the sensitivity of AFP testing and detects HCC earlier among hepatitis C patients with advanced fibrosis or cirrhosis. These data should prompt a reevaluation of how AFP is used in combination with ultrasound in HCC surveillance. PMID- 26260110 TI - Eye drop delivery of pigment epithelium-derived factor-34 promotes retinal ganglion cell neuroprotection and axon regeneration. AB - Axotomised retinal ganglion cells (RGCs) die rapidly by apoptosis and fail to regenerate because of the limited availability of neurotrophic factors and a lack of axogenic stimuli. However, we have recently showed that pigment epithelium derived factor (PEDF) promotes RGC survival and axon regeneration after optic nerve crush injury. PEDF has multiple fragments of the native peptide that are neuroprotective, anti-angiogenic and anti-inflammatory. Here we investigated the neuroprotective and axogenic properties of a fragment of PEDF, PEDF-34, in retinal neurons in vitro and when delivered by intravitreal injection and eye drops in vivo. We found that PEDF-34 was 43% more neuroprotective and 52% more neuritogenic than PEDF-44 in vitro. Moreover, in vivo, intravitreal delivery of 1.88nM PEDF-34 was 71% RGC neuroprotective at 21days after optic nerve crush compared to intact controls, whilst daily eye drops containing 1.88nM PEDF-34 promoted 87% RGC survival. After topical eye drop delivery, PEDF-34 was detected in the vitreous body within 30min and attained physiologically relevant concentrations in the retina by 4h peaking at 1.4+/-0.05nM by 14days. In eye drop compared to intravitreal-treated PEDF-34 animals, 55% more RGC axons regenerated 250MUm beyond the optic nerve lesion. We conclude that daily topical eye drop application of PEDF-34 is superior to weekly intravitreal injections in promoting RGC survival and axon regeneration through both direct effects on retinal neurons and indirect effects on other retinal cells. PMID- 26260111 TI - Amyloid-beta induced astrocytosis and astrocyte death: Implication of FoxO3a-Bim caspase3 death signaling. AB - Astrocytes, the main element of the homeostatic system in the brain, are affected in various neurological conditions including Alzheimer's disease (AD). A common astrocytic reaction in pathological state is known as astrocytosis which is characterized by a specific change in astrocyte shape due to cytoskeletal remodeling, cytokine secretion and cellular proliferation. Astrocytes also undergo apoptosis in various neurological conditions or in response to toxic insults. AD is pathologically characterized by progressive deposition of amyloid beta (Abeta) in senile plaques, intraneuronal neurofibrillary tangles, synaptic dysfunction and neuron death. Astrocytosis and astrocyte death have been reported in AD brain as well as in response to Abeta in vitro. However, how astrocytes undergo both proliferation and death in response to Abeta remains elusive. In this study, we used primary cultures of cortical astrocytes and exposed them to various doses of oligomeric Abeta. We found that cultured astrocytes proliferate and manifest all signs of astrocytosis at a low dose of Abeta. However, at high dose of Abeta the activated astrocytes undergo apoptosis. Astrocytosis was also noticed in vivo in response to Abeta in the rat brain. Next, we investigated the mechanism of astrocyte apoptosis in response to a high dose of Abeta. We found that death of astrocyte induced by Abeta requires a set of molecules that are instrumental for neuron death in response to Abeta. It involves activation of Forkhead transcription factor Foxo3a, induction of its pro-apoptotic target Bim and activation of its downstream molecule, caspase3. Hence, this study demonstrates that the concentration of Abeta decides whether astrocytes do proliferate or undergo apoptosis via a mechanism that is required for neuron death. PMID- 26260112 TI - Prepared to care: adult attachment and filial obligation. AB - OBJECTIVES: Past work found that close adult attachment dimension scores predict caregiver preparedness. Theory and past research suggests filial obligation (FO) may mediate the relationship between attachment and caregiver preparedness. The goal of this study was to test that hypothesis. METHOD: The sample, collected using Mechanical Turk, included 165 women between the ages of 45 and 65 years who were not providing care to an aging parent. Participants were reimbursed $0.75 for completing an online survey assessing response validity, dimensions of adult attachment, depressive symptomatology, FO, and caregiver preparedness, among other variables. The mean participant age was 52.2 years (SD = 5.5). RESULTS: The sample was predominantly White/Caucasian (82.6%), and Black/African American (7.3%). With respect to education, 14.5% completed high school or general education development (GED), 32.7% completed some college, 36.4% completed a Bachelor's degree, and 15.7% completed graduate degrees. The three attachment dimensions (close, dependent, and anxious) and FO were all significantly inner correlated. Stepwise multiple regression analyses found that FO fully mediates the relationship between close attachment and caregiver preparedness, even after controlling for age, education, income, depression, and birth order. CONCLUSION: The primary finding is that FO mediates the relationship between close attachment style and caregiver preparedness among prospective caregivers. This suggests that individual differences in attachment style among prospective caregivers indirectly predict preparedness for future caregiving through FO, suggesting a mechanism relating attachment style and preparation for future care. PMID- 26260113 TI - The timed up and go test for lumbar degenerative disc disease. AB - We report on the use and performance of an objective measure of functional impairment, the timed up and go (TUG) test, in clinical practice for patients with lumbar degenerative disc disease (DDD). We illustrate nine representative patients with lumbar DDD, who were selected from an ongoing prospective study, to report our clinical experience with the TUG test. In addition, a preliminary sample of 30 non-selected consecutive patients is presented. The following parameters were assessed preoperatively, and 3 days and 6 weeks postoperatively: back and leg pain using the visual analogue scale (VAS); functional impairment using the Oswestry disability index (ODI) and Roland-Morris disability index (RMDI); health-related quality of life using the EuroQol 5D (EQ5D) and Short-Form 12 (SF-12). The TUG test results improved by 2.6 and 5.4s after 3 days and 6 weeks compared to the baseline assessment. The mean VAS for back and leg pain decreased by 2.3 and 5.3, respectively, after 3 days, and by 2.7 and 4.6 after 6 weeks. The mean RMDI and ODI decreased by 3.4 and 23.3, respectively, after 3 days, and by 7.0 and 28.0 after 6 weeks. The mean EQ5D increased by 0.38 after 3 days and 0.358 after 6 weeks. The mean SF-12 mental component scale decreased by 0.2 after 3 days and increased by 5.6 after 6 weeks, whereas the mean SF-12 physical component scale increased by 6.4 after 3 days and by 9.8 after 6 weeks. The TUG test proved to be a useful, easy to use tool that could add a new, objective dimension to the armamentarium of clinical tests for the diagnosis and management of DDD. From our preliminary experience, we conclude that the TUG test accurately reflects a patient's objective functional impairment before and after surgery. PMID- 26260114 TI - Predictors of functional outcomes and recurrence of chronic subdural hematomas. AB - We aimed to evaluate the functional outcome and risk factors of recurrence in patients operated on for a chronic subdural hematoma (CSH), and discuss systematic early postoperative CT scans. CSH is a very common disease in neurosurgical practice, especially in elderly patients who are treated with anticoagulation. The challenge is to rapidly restore the independence of these patients. We retrospectively analyzed data from 164 consecutive surgical procedures performed on 140 CSH patients, including recurrent surgery, at our institution from June 2011 to June 2012. Pre- and postoperative CT scans, and medical records, were systematically reviewed using the institutional computing database. A poor functional outcome was defined by a modified Rankin scale (mRS) score>2 at 3 months. Among the 140 patients (mean age 76 years; 64% men), a single burr hole craniostomy was performed in 122 patients, and a craniotomy in 18. A poor functional outcome was recorded in 39 patients (28%; 95% confidence interval [CI] 20-35%). In multivariate analyses, an increased risk of poor functional outcome was associated with age >75 years (odds ratio [OR] 5.88; 95% CI 1.96-17.63), residual hematoma thickness >14 mm (OR 3.79; 95% CI 1.47-9.77), and GCS<15 (OR, 2.96; 95% CI, 1.18-7.40). Recurrences occurred in 24 patients (17%; 95% CI 11-23%), with a median delay to reintervention of 13 days. The independent predictors of CSH recurrence were preoperative anticoagulant therapy (OR 3.68; 95% CI 1.13-12.00), and persistence of mass effect on the postoperative CT scan (OR 5.61; 95% CI 1.52-20.66). Three months after surgical treatment, more than one quarter of the CSH patients had a mRS?3. The loss of independence was associated with older age, initial GCS<15, and residual hematoma thickness postoperatively. Anticoagulant therapy and persistence of postoperative mass effect heightened the risk of recurrence. PMID- 26260115 TI - SLC44A1-PRKCA fusion in papillary and rosette-forming glioneuronal tumors. AB - We investigated the fused protein of solute carrier family 44 choline transporter member 1 (SLC44A1) and protein kinase C alpha (PRKCA) in three patients with papillary glioneuronal tumors (PGNT). PGNT and rosette-forming glioneuronal tumors (RGNT) are recently identified, unusual glioneuronal tumor variants which were categorized as novel tumor entities in the 2007 World Health Organization classification system. The molecular background of these tumors remains poorly understood due to the paucity of studies. The SLC44A1-PRKCA fusion was recently detected in three cases of PGNT. We invesitgated for the SLC44A1-PRKCA fusion protein in the three PGNT patients and a further two with RGNT using fluorescence in situ hybridization. Two out of the three PGNT patients had a fused signal (paired red-green signal) representing a rearrangement on chromosomes 9 and 17. A normal signal pattern was observed in the third PGNT patient. Neither of the two RGNT patients demonstrated a fused signal. This suggests that the SLC44A1-PRKCA fusion is a characteristic alteration in PGNT but not RGNT. Therefore, it is a potential biomarker of PGNT. The paired red-green signal that was observed in the PGNT patients implies the presence of a different breakpoint than that previously reported in the 9q31 and 17q24 genes. PMID- 26260116 TI - Intramedullary spinal metastasis of a carcinoid tumor. AB - We report an intramedullary spinal cord metastasis from a bronchial carcinoid, and discuss its mechanisms and management. Intramedullary spinal cord metastases from any cancer are rare, and bronchial carcinoids account for only a small fraction of lung cancers. To our knowledge, an intramedullary spinal cord metastasis from a bronchial carcinoid has been described only once previously. PMID- 26260117 TI - Can the KG1 cell line be used as a model of dendritic cells and discriminate the sensitising potential of chemicals? AB - The KG1 myeloid leukaemia was used as source of dendritic cells (DC) to discriminate between respiratory and contact sensitising chemicals. A cocktail of cytokines was used to differentiate KG1 to dendritic like cells (termed dKG1) and the effects of nine chemicals (respiratory and contact sensitisers) and an irritant control on surface marker expression, 'antigen presenting' function and cytokine expression investigated. The stability of these chemicals when dissolved was characterised using MALDI ToF MS. A Hill plot model was used with the cellular viability data to quantify the lethal dose 50% (LD50) and a maximum sub toxic concentration of each chemical defined. Cytokine expression by the treated dKG1 was quantified using multiplex immunobead analysis. Whilst dKG1 cells were morphologically similar to DCs, expression of specific surface markers was not typical for DCs derived from healthy precursor cells. When the chemicals were applied at defined sub toxic doses no effects on dKG1 phenotype, function, or cytokine expression, attributable to the sensitisation properties were discriminated. However, dKG1 cells were much more sensitive to the toxic effects of these chemicals compared to the parent KG1 cells. Only 4 of the 9 chemicals tested were stable when dissolved indicating that the effect of sensitising chemicals on antigen presenting cells may be related to species other than the parent compound. PMID- 26260118 TI - Botulinum toxin B increases intrinsic muscle activity in organotypic spinal cord skeletal muscle co-cultures. AB - In organotypic spinal cord-skeletal muscle co-cultures, motoneurons are driven by locomotor commands and induce contractions in surrounding muscle fibres. Using these co-cultures, it has been shown that effects of organophosphorus compounds on neuromuscular synapses can be determined in vitro. In the present study we aimed to extend this in vitro tool for pharmacologic testing of botulinum toxin B. This neurotoxin is widely used for the treatment of dystonia. Besides its effects on the neuromuscular junction, botulinum toxins may also act at centrally located synapses. Incubation with botulinum toxin B (Neurobloc((r))) induced a significant increase in muscular activity after 24, 48 and 72h. Application of the NMDA- and AMPA-receptor antagonists AP5 (20MUM) and CNQX (15MUM) induced a similar augmentation of muscle activity after 48 and 72h, respectively. Administration of the glycine- and GABA(A)-receptor antagonists strychnine (1MUM) and bicuculline (100MUM) did not alter intrinsic muscle activity. In contrast, application of a non-depolarizing muscle relaxant rocuronium bromide reduced the muscle activity in a dose-dependent manner. Our findings suggest that glutamatergic synapses in the spinal cord are more sensitive to botulinum toxin B than synaptic contacts between spinal motoneurons and muscle fibres. PMID- 26260119 TI - A new dry-surface biofilm model: An essential tool for efficacy testing of hospital surface decontamination procedures. AB - The environment has been shown to be a source of pathogens causing infections in hospitalised patients. Incorporation of pathogens into biofilms, contaminating dry hospital surfaces, prolongs their survival and renders them tolerant to normal hospital cleaning and disinfection procedures. Currently there is no standard method for testing efficacy of detergents and disinfectants against biofilm formed on dry surfaces. AIM: The aim of this study was to develop a reproducible method of producing Staphylococcus aureus biofilm with properties similar to those of biofilm obtained from dry hospital clinical surfaces, for use in efficacy testing of decontamination products. The properties (composition, architecture) of model biofilm and biofilm obtained from clinical dry surfaces within an intensive care unit were compared. METHODS: The CDC Biofilm Reactor was adapted to create a dry surface biofilm model. S. aureus ATCC 25923 was grown on polycarbonate coupons. Alternating cycles of dehydration and hydration in tryptone soy broth (TSB) were performed over 12 days. Number of biofilm bacteria attached to individual coupons was determined by plate culture and the coefficient of variation (CV%) calculated. The DNA, glycoconjugates and protein content of the biofilm were determined by analysing biofilm stained with SYTO 60, Alexa-488-labelled Aleuria aurantia lectin and SyproOrange respectively using Image J and Imaris software. Biofilm architecture was analysed using live/dead staining and confocal microscopy (CM) and scanning electron microscopy (SEM). Model biofilm was compared to naturally formed biofilm containing S. aureus on dry clinical surfaces. RESULTS: The CDC Biofilm reactor reproducibly formed a multi-layered, biofilm containing about 10(7) CFU/coupon embedded in thick extracellular polymeric substances. Within run CV was 9.5% and the between run CV was 10.1%. Protein was the principal component of both the in vitro model biofilm and the biofilms found on clinical surfaces. Continued dehydration and ageing of the model biofilm for 30 days increased the % of protein, marginally decreased gylcoconjugate % but reduced extracellular DNA by 2/3. The surface of both model and clinical biofilms was rough reflecting the heterogeneous nature of biofilm formation. The average maximum thickness was 30.74+/-2.1 MUm for the in vitro biofilm model and between 24 and 47 MUm for the clinical biofilms examined. CONCLUSION: The laboratory developed biofilm was similar to clinical biofilms in architecture and composition. We propose that this method is suitable for evaluating the efficacy of surface cleaners and disinfectants in removing biofilm formed on dry clinical surfaces as both within run and between run variation was low, and the required equipment is easy to use, cheap and readily available. PMID- 26260120 TI - Sunscreen remanence on the skin: a noninvasive real time in vivo spectral analysis assessing the quenching of specular ultraviolet A light reflectance. AB - BACKGROUND: Under specific light illumination, particularly ultraviolet radiation (UVR), the skin produces both specular light reflectance and, possibly, specific fluorescent emission. A quenching effect of fluorescence is observed following the application of sunscreens active against UVA radiations. AIMS: To assess noninvasively in a real-time process, the potential sunscreen remanence/substantivity after application on the skin. METHODS: The Visiopor(r) device was used in a real-time procedure after application of sunscreens to the skin. A quenching effect of follicular fluorescence due to bacterial porphyrins was evaluated at 30-min intervals. The Visioscan((r)) device was used as a distinct UVA emitter in a control procedure of spectral analysis of specular UVR emission and reflectance by dermal fibers. RESULTS: Under UVA-1 irradiations, facial skin produced different patterns of specular UVR reflectance and fluorescent emission as well. The porphyrin-related follicular fluorescence was instantly abated by UVA blockers present in suncare products. The potential sunscreen remanence/substantivity was assessed by the follicular and interfollicular fluorescence recurrence all along the next hours. CONCLUSIONS: All UVA blocker-containing suncare products exhibited a similar overall quenching effect on porphyrin-enriched facial hair follicles and dermal fibers. This effect lasted for a few hours. Differences in the fluorescence recovery were likely related to the amount in suncare application and the nature of the formulation components. PMID- 26260121 TI - A new group of eubacterial light-driven retinal-binding proton pumps with an unusual cytoplasmic proton donor. AB - One of the main functions of microbial rhodopsins is outward-directed light driven proton transport across the plasma membrane, which can provide sources of energy alternative to respiration and chlorophyll photosynthesis. Proton-pumping rhodopsins are found in Archaea (Halobacteria), multiple groups of Bacteria, numerous fungi, and some microscopic algae. An overwhelming majority of these proton pumps share the common transport mechanism, in which a proton from the retinal Schiff base is first transferred to the primary proton acceptor (normally an Asp) on the extracellular side of retinal. Next, reprotonation of the Schiff base from the cytoplasmic side is mediated by a carboxylic proton donor (Asp or Glu), which is located on helix C and is usually hydrogen-bonded to Thr or Ser on helix B. The only notable exception from this trend was recently found in Exiguobacterium, where the carboxylic proton donor is replaced by Lys. Here we describe a new group of efficient proteobacterial retinal-binding light-driven proton pumps which lack the carboxylic proton donor on helix C (most often replaced by Gly) but possess a unique His residue on helix B. We characterize the group spectroscopically and propose that this histidine forms a proton-donating complex compensating for the loss of the carboxylic proton donor. PMID- 26260122 TI - Risks and benefits in treatment of mediastinal abscess by endobronchial ultrasound-guided transbronchial needle aspiration. AB - INTRODUCTION: Mediastinal abscess is a fatal condition, treatment of mediastinal abscess is with antibiotics and sometimes surgery for debridement and drainage. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a safe assessment and candidate treatment method of mediastinal lesions. OBJECTIVES: This study aimed to HYPERLINK "javascript:void(0);" discuss risks and benefits in treatment of mediastinal abscess by EBUS-TBNA. METHODS: We noticed a 56-year-old man with developed bilateral pneumonia and sepsis after puncture of mediastinal abscess by EBUS-TBNA. The patient was successfully treated with a combination of systemic anti-infection treatment and intracavitary administration of antibiotics, antifungal and repeated drainage and lavage via EBUS-TBNA, in 1 year follow-up without recurrence. RESULTS: This study indicated infection spread risk of mediastinal abscess after EBUS-TBNA, and mediastinal abscess was successfully cured by combination of systemic anti-infection and local intervention through EBUS-TBNA. CONCLUSION: EBUS-TBNA is a potential effective minimally invasive treatment for mediastinal abscess, and it is necessary to be aware of clinical complications after puncture of mediastinal infectious lesions by EBUS-TBNA. PMID- 26260123 TI - Modeling nanoparticle wrapping or translocation in bilayer membranes. AB - The spontaneous wrapping of nanoparticles by membranes is of increasing interest as nanoparticles become more prevalent in consumer products and hence more likely to enter the human body. We introduce a simulations-based tool that can be used to visualize the molecular level interaction between nanoparticles and bilayer membranes. By combining LIME, an intermediate resolution, implicit solvent model for phospholipids, with discontinuous molecular dynamics (DMD), we are able to simulate the wrapping or embedding of nanoparticles by 1,2-dipalmitoyl-sn-glycero 3-phosphocholine (DPPC) bilayer membranes. Simulations of hydrophilic nanoparticles with diameters from 10 A to 250 A show that hydrophilic nanoparticles with diameters greater than 20 A become wrapped while the nanoparticle with a diameter of 10 A does not. Instead this smaller particle became embedded in the bilayer surface where it can interact with the hydrophilic head groups of the lipid molecules. We also investigate the interaction between a DPPC bilayer and hydrophobic nanoparticles with diameters 10 A to 40 A. These nanoparticles do not undergo the wrapping process; instead they directly penetrate the membrane and embed themselves within the inner hydrophobic core of the bilayers. PMID- 26260124 TI - The Association between Pre-existing Diabetes Mellitus and Pressure Ulcers in Patients Following Surgery: A Meta-analysis. AB - Uncertainty exists about the role of diabetes in the development of surgery related pressure ulcers. Therefore, we conducted a meta-analysis to explore the association between pre-existing diabetes mellitus and pressure ulcers among patients after surgery. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random effects models. Thirteen eligible studies of 2367 patients in total and 12,053 controls were included in the final analysis. Compared with patients without diabetes, the pooled odds ratio (OR) of the incidence of pressure ulcers in diabetic patients was 1.74 [95% confidence interval (CI) = 1.40-2.15, I(2 )= 51.1%]. Estimates by type of surgery suggested similar results in cardiac surgery [OR = 2.00, 95% CI = 1.42-2.82, I(2 )= 0%], in general surgery [OR = 1.75, 95% CI = 1.42-2.15, I(2 )= 0%], and in major lower limb amputations [OR = 1.65, 95% CI = 1.01-2.68, I(2 )= 0%] for diabetic patients versus non-diabetic controls. We did not find an increased incidence of pressure ulcers in diabetic patients undergoing hip surgery compared with non-diabetic controls [OR = 1.46, 95% CI = 0.62-3.47, I(2 )= 93.1%]. The excess risk of pressure ulcers associated with pre-existing diabetes was significantly higher in patients undergoing surgery, specifically in patients receiving cardiac surgery. Further studies should be conducted to examine these associations in other types of surgery. PMID- 26260125 TI - Factors that affect the job satisfaction of Saudi Arabian nurses. AB - AIM: To determine factors that influence the job satisfaction of Saudi nurses. BACKGROUND: Saudi Arabia has a chronic shortage of Saudi national nurses. This research contributes to a greater understanding of how job satisfaction influences the recruitment and retention of Saudi nationals within the nursing profession. METHODS: Qualitative data were gathered from Saudi nurses and content analysis was used to identify themes in the written responses. RESULTS: Four main themes emerged from the data: lack of educational opportunities and support and the poor image of the nursing profession, perceptions of favouritism, high workloads and stressful work environment and the effect of religion on job satisfaction. CONCLUSIONS: Saudi nurses would be more satisfied with their jobs if they had greater access to educational opportunities and if there was a reduction in workload and the perceived favouritism in the workplace was addressed. Religion was also found to play a significant role in supporting job satisfaction. IMPLICATIONS FOR NURSING MANAGEMENT: These findings suggest the development of educational scholarships, as well as policies that better support equity in the workplace, to address Saudi nurses' level of job satisfaction. The generally positive impact of cultural and religious beliefs is also highlighted in this study. PMID- 26260126 TI - Membrane potential governs calcium influx into microvascular endothelium: integral role for muscarinic receptor activation. AB - In resistance arteries, coupling a rise of intracellular calcium concentration ([Ca(2+)]i) to endothelial cell hyperpolarization underlies smooth muscle cell relaxation and vasodilatation, thereby increasing tissue blood flow and oxygen delivery. A controversy persists as to whether changes in membrane potential (V(m)) alter endothelial cell [Ca(2+)]i. We tested the hypothesis that V(m) governs [Ca(2+)]i in endothelium of resistance arteries by performing Fura-2 photometry while recording and controlling V(m) of intact endothelial tubes freshly isolated from superior epigastric arteries of C57BL/6 mice. Under resting conditions, [Ca(2+)]i did not change when V(m) shifted from baseline (~-40 mV) via exposure to 10 MUM NS309 (hyperpolarization to ~-80 mV), via equilibration with 145 mm [K(+)]o (depolarization to ~-5 mV), or during intracellular current injection (+/-0.5 to 5 nA, 20 s pulses) while V(m) changed linearly between ~-80 mV and +10 mV. In contrast, during the plateau (i.e. Ca(2+) influx) phase of the [Ca(2+)]i response to approximately half-maximal stimulation with 100 nm ACh (~EC50), [Ca(2+)]i increased as V(m) hyperpolarized below -40 mV and decreased as V(m) depolarized above -40 mV. The magnitude of [Ca(2+)]i reduction during depolarizing current injections correlated with the amplitude of the plateau [Ca(2+)]i response to ACh. The effect of hyperpolarization on [Ca(2+)]i was abolished following removal of extracellular Ca(2+), was enhanced subtly by raising extracellular [Ca(2+)] from 2 mm to 10 mm and was reduced by half in endothelium of TRPV4(-/-) mice. Thus, during submaximal activation of muscarinic receptors, V(m) can modulate Ca(2+) entry through the plasma membrane in accord with the electrochemical driving force. PMID- 26260127 TI - Phylogenetic analysis of eight sudanese camel contagious ecthyma viruses based on B2L gene sequence. AB - BACKGROUND: Camel contagious ecthyma (CCE) is an important viral disease of camelids caused by a poxvirus of the genus parapoxvirus (PPV) of the family Poxviridae. The disease has been reported in west and east of the Sudan causing economical losses. However, the PPVs that cause the disease in camels of the Sudan have not yet subjected to genetic characterization. At present, the PPV that cause CCE cannot be properly classified because only few isolates that have been genetically analyzed. METHODS AND RESULTS: PCR was used to amplify the B2L gene of the PPV directly from clinical specimens collected from dromedary camels affected with contagious ecthyma in the Sudan between 1993 and 2013. PCR products were sequenced and subjected to genetic analysis. The results provided evidence for close relationships and genetic variation of the camel PPV (CPPV) represented by the circulation of both Pseudocowpox virus (PCPV) and Orf virus (ORFV) strains among dromedary camels in the Sudan. Based on the B2L gene sequence the available CPPV isolates can be divided into two genetic clades or lineages; the Asian lineage represented by isolates from Saudi Arabia, Bahrain and India and the African lineage comprising isolates from the Sudan. CONCLUSION: The camel parapoxvirus is genetically diverse involving predominantly viruses close to PCPV in addition to ORFVs, and can be divided into two genetically distant lineages. Based on sequences of the B2L gene it is not possible to suggest that the viruses that cause CCE form a monophylogenetic group or species within the PPV phylogeny. PMID- 26260128 TI - Living conditions are associated with increased antibiotic resistance in community isolates of Escherichia coli. AB - OBJECTIVES: The objective of this study was to measure the associations between domains of deprivation and antibiotic resistance of Escherichia coli. METHODS: Routine surveillance data for antibiotic susceptibility of E. coli isolates were obtained from urine specimens taken from patients presenting with suspected urinary tract infection in 2010-12 to healthcare practitioners based in the community in Leeds and Bradford. Eight antibiotics were included in the analyses. Postcodes were linked to lower super output areas (average populations of 1500). The 2010 Indices of Deprivation were used as neighbourhood characteristics for each lower super output area. Multilevel logistic regression models were used to estimate the independent effect of structural components on the odds of resistance to each antibiotic. RESULTS: With respect to living conditions, residence in the most-deprived areas compared with the least-deprived areas was associated with increased odds of antibiotic resistance for all eight antibiotics analysed. The magnitude of these associations included an OR of 2.04 (95% CI 1.03 3.07) for cefalexin, 2.16 (95% CI 1.16-4.05) for ciprofloxacin, 2.47 (95% CI 1.08 5.66) for nitrofurantoin and 1.33 (95% CI 1.07-1.75) for trimethoprim. CONCLUSIONS: Social deprivation in the form of living conditions is associated with increased antibiotic resistance for E. coli. This evidence suggests there is a need for further individual-level studies to explore the potential mechanism for these associations. PMID- 26260129 TI - Coexistence of a novel KPC-2-encoding MDR plasmid and an NDM-1-encoding pNDM HN380-like plasmid in a clinical isolate of Citrobacter freundii. AB - OBJECTIVES: The objective of this study was to characterize the molecular mechanism of coproduction of KPC-2 and NDM-1 in Citrobacter freundii. METHODS: C. freundii strain 112298 was isolated from a human case of septic shock in a Chinese teaching hospital. The major carbapenemase and ESBL genes were detected by PCR. The MIC values were determined by using VITEK 2 and antimicrobial susceptibility was judged by CLSI standards. The resistance plasmid was transferred into Escherichia coli by electroporation, followed by plasmid DNA isolation from the electroporant, and then fully sequenced and compared with closely related plasmids. RESULTS: Strain 112298 produces KPC-2 and NDM-1, encoded by the novel non-typeable plasmid p112298-KPC and an IncX3-type plasmid p112298-NDM, respectively. In p112298-KPC, a Tn1722-based blaKPC-2-carrying transposon is associated with several additional resistance modules, constituting a single MDR region. Assembly of these resistance modules is likely mediated by homologous recombination between five copies of IS26 elements at different sites within the MDR region. p112298-NDM is a very close relation of pNDM-HN380. blaNDM 1 in p112298-NDM is carried by a Tn125 variant, which differs from the prototype Tn125 as observed in pNDM-BJ01 by disruption of an upstream copy of ISAba125 by IS5 and absence of a downstream copy of ISAba125. CONCLUSIONS: Production of KPC 2 and NDM-1 by p112298-KPC and p112298-NDM, respectively, makes C. freundii 112298 highly resistant to carbapenems and, moreover, these two plasmids still harbour genes for resistance to cephalosporins, chloramphenicol, chromate, fosfomycin, quaternary ammonium, rifampicin and sulphonamides. PMID- 26260130 TI - In vivo evolution of resistance of Pseudomonas aeruginosa strains isolated from patients admitted to an intensive care unit: mechanisms of resistance and antimicrobial exposure. AB - OBJECTIVES: The main objective of this study was to investigate the relationship among the in vivo acquisition of antimicrobial resistance in Pseudomonas aeruginosa clinical isolates, the underlying molecular mechanisms and previous exposure to antipseudomonal agents. METHODS: PFGE was used to study the molecular relatedness of the strains. The MICs of ceftazidime, cefepime, piperacillin/tazobactam, imipenem, meropenem, ciprofloxacin and amikacin were determined. Outer membrane protein profiles were assessed to study OprD expression. RT-PCR was performed to analyse ampC, mexB, mexD, mexF and mexY expression. The presence of mutations was analysed through DNA sequencing. RESULTS: We collected 17 clonally related paired isolates [including first positive samples (A) and those with MICs increased >=4-fold (B)]. Most B isolates with increased MICs of imipenem, meropenem and ceftazidime became resistant to these drugs. The most prevalent resistance mechanisms detected were OprD loss (65%), mexB overexpression (53%), ampC derepression (29%), quinolone target gene mutations (24%) and increased mexY expression (24%). Five (29%) B isolates developed multidrug resistance. Meropenem was the most frequently (71%) received treatment, explaining the high prevalence of oprD mutations and likely mexB overexpression. Previous exposure to ceftazidime showed a higher impact on selection of increased MICs than previous exposure to piperacillin/tazobactam. CONCLUSIONS: Stepwise acquisition of resistance has a critical impact on the resistance phenotypes of P. aeruginosa, leading to a complex scenario for finding effective antimicrobial regimens. In the clinical setting, meropenem seems to be the most frequent driver of multidrug resistance development, while piperacillin/tazobactam, in contrast to ceftazidime, seems to be the beta-lactam least associated with the selection of resistance mechanisms. PMID- 26260131 TI - Evaluation of the RAPIDEC(r) CARBA NP, the Rapid CARB Screen(r) and the Carba NP test for biochemical detection of carbapenemase-producing Enterobacteriaceae. AB - OBJECTIVES: The objective of this study was the evaluation of the performance of two commercially available biochemical tests for the rapid detection of carbapenemase-producing Enterobacteriaceae compared with a home-made technique. METHODS: A collection of 150 enterobacterial isolates, including 132 isolates with decreased susceptibility to at least one carbapenem molecule, were tested for carbapenemase activity using the RAPIDEC((r)) CARBA NP (bioMerieux), the Rapid CARB Screen((r)) (Rosco Diagnostica) and the home-made Carba NP test. This strain collection included 55 non-carbapenemase producers, 21 KPC producers, 21 NDM producers, 17 VIM producers, 11 IMP producers, 16 OXA-48 producers and 9 OXA 48-like producers (OXA-162, OXA-181, OXA-204, OXA-232 and OXA-244). RESULTS: The RAPIDEC((r)) CARBA NP detected all carbapenemase producers except a single OXA 244 producer. Using the Rapid CARB Screen((r)), one KPC-2, two NDM-1, one OXA-48 and five OXA-48 variant producers gave equivocal results and one OXA-244 producer was not detected. Using the Carba NP test, the same OXA-244 producer was not detected and one OXA-181 producer and one OXA-244 producer gave equivocal results. Sensitivity and specificity were 99% (95% CI 94.3%-99.8%) and 100% (95% CI 93.5%-100%), respectively, for the RAPIDEC((r)) CARBA NP test, 89.5% (95% CI 81.7%-94.2%) and 70.9% (95% CI 57.9%-81.2%) for the Rapid CARB Screen((r)) and 96.8% (95% CI 91.1%-98.9%) and 100% (95% CI 93.5%-100%) for the Carba NP test. The impact of the use of an adequate bacterial inoculum for obtaining the optimal performance with the RAPIDEC((r)) CARBA NP was noted. CONCLUSIONS: The RAPIDEC((r)) CARBA NP possesses the best performance for rapid and efficient detection of carbapenemase-producing Enterobacteriaceae. PMID- 26260132 TI - Use of fluoroquinolones for the treatment of TB: 8 years of experience. PMID- 26260134 TI - Variations in Cannabis Use Level and Correlates in Opiate-Users on Methadone Maintenance Treatment: A French Prospective Study. AB - INTRODUCTION: Concurrent cannabis use is very frequent among opioid users on methadone maintenance treatment (MMT), which could reflect a coping strategy during MMT. The aims of this study were to describe variations in cannabis use and to explore whether MMT could modify the patterns of cannabis use correlates. METHODS: The sample included 188 opioid-dependent individuals who initiated MMT and were prospectively followed for 12 months. Cannabis use was monitored at enrollment and at months 3, 6 and 12. The relationships between cannabis use level (non-daily use and daily use vs. no use in the previous month) and its determinants (socioeconomic factors, substance use characteristics and mental health) were explored using mixed multinomial logistic regressions. RESULTS: No significant variation trend in cannabis use levels was observed during the follow up period among the 188 subjects analyzed (p=0.85). After adjustment for socio demographic factors, opioid use was associated with both non-daily (OR=3.11, p=0.01) and daily cannabis use (OR=2.58, p=0.04). Moreover the number of health problems reported was associated with daily cannabis use (OR=1.12 per 1-problem increase, p=0.004). The factors associated with cannabis use appeared similar before and after starting treatment (no significant interaction observed between MMT and any factor). CONCLUSIONS: Cannabis use during MMT more likely reflects pre-existing common liability to substance use or self-medication practices towards health problems than a behavior aimed at managing problems with MMT. With recent research suggesting an interaction between cannabinoid and opioid systems, the benefit of cannabis-based pharmacotherapies during MMT should be further explored in addiction research. PMID- 26260133 TI - Persistent pain alters AMPA receptor subunit levels in the nucleus accumbens. AB - BACKGROUND: A variety of pain conditions have been found to be associated with depressed mood in clinical studies. Depression-like behaviors have also been described in animal models of persistent or chronic pain. In rodent chronic neuropathic pain models, elevated levels of GluA1 subunits of alpha-amino-3 hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the nucleus accumbens (NAc) have been found to inhibit depressive symptoms. However, the effect of reversible post-surgical pain or inflammatory pain on affective behaviors such as depression has not been well characterized in animal models. Neither is it known what time frame is required to elicit AMPA receptor subunit changes in the NAc in various pain conditions. RESULTS: In this study, we compared behavioral and biochemical changes in three pain models: the paw incision (PI) model for post-incisional pain, the Complete Freund's Adjuvant (CFA) model for persistent but reversible inflammatory pain, and the spared nerve injury (SNI) model for chronic postoperative neuropathic pain. In all three models, rats developed depressive symptoms that were concurrent with the presentation of sensory allodynia. GluA1 levels at the synapses of the NAc, however, differed in these three models. The level of GluA1 subunits of AMPA-type receptors at NAc synapses was not altered in the PI model. GluA1 levels were elevated in the CFA model after a period (7 d) of persistent pain, leading to the formation of GluA2-lacking AMPA receptors. As pain symptoms began to resolve, however, GluA1 levels returned to baseline. Meanwhile, in the SNI model, in which pain persisted beyond 14 days, GluA1 levels began to rise after pain became persistent and remained elevated. In addition, we found that blocking GluA2 lacking AMPA receptors in the NAc further decreased the depressive symptoms only in persistent pain models. CONCLUSION: Our study shows that while both short-term and persistent pain can trigger depression-like behaviors, GluA1 upregulation in the NAc likely represents a unique adaptive response to minimize depressive symptoms in persistent pain states. PMID- 26260135 TI - Examining the Preliminary Efficacy of a Dating Violence Prevention Program for Hispanic Adolescents. AB - The purpose of this study is to evaluate the preliminary efficacy of a dating violence (DV) prevention program for Cuban American adolescents (JOVEN/YOUTH: Juntos Opuestos a la Violence Entre Novios/Together Against Dating Violence). A randomized-controlled experimental design with a delayed condition was used to evaluate the effects on DV victimization and perpetration (N = 82). Self administrated assessments were completed at baseline, 1 week, 3 months, and 12 months after the intervention to assess for psychological victimization and perpetration and physical and sexual victimization and perpetration. Effect sizes were estimated, and generalized estimating equations were generated to test intervention effects over time and potential gender interactions. The intervention had medium to strong effects on DV victimization and perpetration for male participants but not for females. However, intervention effects were not statistically significant over time. More research is needed to enhance intervention effects of JOVEN on DV outcomes and to evaluate these effects among a larger and more diverse sample. PMID- 26260136 TI - Off-Label Prescribing by Psychiatrists: What is the Practitioner's Liability? AB - In psychiatry, the molecules available and the dosages recommended when a drug receives marketing authorization are not always adequate to treat patients with major behavioral disturbances. Off-label prescribing is frequent in this context, with regard to the indications and the dosages given as well as to the drug combinations used. However, if complications or death occur, the practitioner's liability may be engaged. The authors report three deaths attributed to off-label prescribing in psychiatry and which led to charges against the physicians. They review the precautions to be taken when prescribing in such conditions (no other possible treatment, existence of sound scientific evidence, consent obtained from the patient, or their legal representatives except in cases of force majeure) and the physician's liability if adverse events occur that could be attributed to off label prescribing. PMID- 26260137 TI - Identification of immediate early response protein 2 as a regulator of angiogenesis through the modulation of endothelial cell motility and adhesion. AB - Human immediate early response 2 (IER2) has been characterized as a putative nuclear protein that functions as a transcription factor or transcriptional co activator in the regulation of cellular responses, and may be involved in the regulation of tumor progression and metastasis. Data from our previous gene expression profile of the human microvascular endothelial cells during capillary morphogenesis showed a significant alteration of IER2 expression, suggesting that IER2 may participate in the regulation of the endothelial cell morphogenesis and angiogenesis. The aim of the present study was to investigate the role of IER2 in cell motility, cell-matrix adhesion and in vitro capillary-like structures formation of the human umbilical vein endothelium cells (HUVECs). IER2 was constitutively expressed in HUVECs, and lentiviral-mediated depletion of IER2 significantly reduced the cell motility, cell-matrix adhesion and capillary-like structures formation of HUVECs. Results also showed that depletion and overexpression of IER2 altered the actin cytoskeleton rearrangement in HUVECs. Furthermore, results from western blot analysis showed that the activity of the focal adhesion kinase (FAK) can be regulated by IER2. These results indicated that IER2 regulates endothelial cell motility, adhesion on collagen type I matrix and the capillary tube formation, as the result of the regulation of the actin cytoskeleton rearrangement presumably via a FAK-dependent mechanism. PMID- 26260138 TI - Real-time histological imaging of kidneys stained with food dyes using multiphoton microscopy. AB - We have developed a real-time imaging technique for diagnosis of kidney diseases which is composed of two steps, staining renal cells safely with food dyes and optical sectioning of living renal tissue to obtain histological images by multiphoton microscopy (MPM). Here, we demonstrated that the MPM imaging with food dyes, including erythrosine and indigo carmine, could be used as fluorescent agents to visualize renal functions and structures such as glomerular bloodstreams, glomerular filtration, and morphology of glomeruli and renal tubules. We also showed that the kidneys of IgA nephropathy model-mice stained with the food dyes presented histopathological characteristics different from those observed in normal kidneys. The use of the food dyes enhances the quality of tissue images obtained by MPM and offers the potential to contribute to a clinical real-time diagnosis of kidney diseases. PMID- 26260139 TI - Food insecurity reported by children, but not by mothers, is associated with lower quality of diet and shifts in foods consumed. AB - Household food security shows little indication of nutrient inadequacy among children, according to reports made by parents. We examined the associations of food insecurity as reported by children and mothers with children's consumption of energy, macronutrients such as vitamin A, calcium, iron and zinc, and selected foods, and whether these associations differed by child's gender. This cross sectional study had non-probabilistic 128 Venezuelan mother-child pairs. We assessed food insecurity and management strategies in children using 10- and nine item instruments, respectively. Mothers' report of food insecurity came from a previously validated 12-item instrument. Nutrient intake of children was assessed with a 67-item food frequency questionnaire. Comparisons were made using chi square test for contingency tables and t-tests for trends (P < 0.05). Linear regression models were used for intakes of nutrients and selected foods. We tested for interactions with gender. Prevalence of child- and mother-reported food insecurity was 83.6 and 61.7%, respectively (P < 0.01). Greater food insecurity or management strategies reported by boys was associated with lower calcium, iron and zinc intake (P < 0.05), but reported intakes were low in girls who are even food secure. Rice and corn flour consumption was higher with higher food insecurity in children. Papaya and banana were less consumed by food insecure children. We found shifts in 13 of 67 foods consumed, with less quality in those food insecure, as reported by children. Mother-reported food insecurity was associated only with rice intake of children. In contrast to mothers' reports, food insecurity reported by children was associated with children's lower quality of diet and shifts in foods consumed. PMID- 26260140 TI - High rate of hematological responses to sorafenib in FLT3-ITD acute myeloid leukemia relapsed after allogeneic hematopoietic stem cell transplantation. AB - Relapse represents the most significant cause of failure of allogeneic hematopoietic stem cell transplantation (HSCT) for FLT3-ITD-positive acute myeloid leukemia (AML), and available therapies are largely unsatisfactory. In this study, we retrospectively collected data on the off-label use of the tyrosine kinase inhibitor sorafenib, either alone or in association with hypomethylating agents and adoptive immunotherapy, in 13 patients with post transplantation FLT3-ITD-positive AML relapses. Hematological response was documented in 12 of 13 patients (92%), and five of 13 (38%) achieved complete bone marrow remission. Treatment was overall manageable in the outpatient setting, although all patients experienced significant adverse events, especially severe cytopenias (requiring a donor stem cell boost in five patients) and typical hand-foot syndrome. None of the patients developed graft-vs.-host disease following sorafenib alone, whereas this was frequently observed when this was given in association with donor T-cell infusions. Six patients are alive and in remission at the last follow-up, and four could be bridged to a second allogeneic HSCT, configuring a 65 +/- 14% overall survival at 100 d from relapse. Taken together, our data suggest that sorafenib might represent a valid treatment option for patients with FLT3-ITD-positive post-transplantation relapses, manageable also in combination with other therapeutic strategies. PMID- 26260142 TI - Obesity: Liraglutide--another weapon in the war against obesity? PMID- 26260143 TI - Pancreas: Fatty pancreas linked to increased BMI and insulin resistance in children. PMID- 26260141 TI - Short-chain fatty acids in control of body weight and insulin sensitivity. AB - The connection between the gut microbiota and the aetiology of obesity and cardiometabolic disorders is increasingly being recognized by clinicians. Our gut microbiota might affect the cardiometabolic phenotype by fermenting indigestible dietary components and thereby producing short-chain fatty acids (SCFA). These SCFA are not only of importance in gut health and as signalling molecules, but might also enter the systemic circulation and directly affect metabolism or the function of peripheral tissues. In this Review, we discuss the effects of three SCFA (acetate, propionate and butyrate) on energy homeostasis and metabolism, as well as how these SCFA can beneficially modulate adipose tissue, skeletal muscle and liver tissue function. As a result, these SCFA contribute to improved glucose homeostasis and insulin sensitivity. Furthermore, we also summarize the increasing evidence for a potential role of SCFA as metabolic targets to prevent and counteract obesity and its associated disorders in glucose metabolism and insulin resistance. However, most data are derived from animal and in vitro studies, and consequently the importance of SCFA and differential SCFA availability in human energy and substrate metabolism remains to be fully established. Well-controlled human intervention studies investigating the role of SCFA on cardiometabolic health are, therefore, eagerly awaited. PMID- 26260144 TI - Bone: Sequential osteoporosis treatment--the order of things. PMID- 26260147 TI - Food and nutrition security: challenges of post-harvest handling in Kenya. AB - Presently, close to 1 billion people suffer from hunger and food insecurity. Statistics in Kenya indicates that over 10 million people suffer from chronic food insecurity and poor nutrition, 2-4 million people require emergency food assistance at any given time with nearly 30 % of Kenya's children being undernourished, 35 % stunted while micro-nutrient deficiency is wide spread. Key among the challenges contributing to inadequate foods include lack of certified seeds, seasonal production (rain-fed), high post-harvest losses and wastages, poor transportation, low value additions which reduce their market competitiveness. The present paper examines some of the underlying causes for high food wastage experience in Kenya and the associated challenges in addressing these problems. The paper also provides an overview of some of the basic solutions that have been recommended by various stakeholders. However, in spite of the recent efforts made to mitigate food wastage, there is still an urgent need to address these gaps through participatory, innovative community based interventions that will create resilience to climate change and enhance livelihoods of smallholder farmers in diverse ecosystems. PMID- 26260148 TI - Photoinduced Reactivity of the Soft Hydrotris(6-tert-butyl-3 thiopyridazinyl)borate Scorpionate Ligand in Sodium, Potassium, and Thallium Salts. AB - The soft scorpionate ligand hydrotris(6-tert-butyl-3-thiopyridazinyl)borate (Tn) was found to exhibit pronounced photoreactivity. Full elucidation of this process revealed the formation of 6-tert-butylpyridazine-3-thione (PnH) and 4,5-dihydro-6 tert-butylpyridazine-3-thione (H2PnH). Under exclusion of light, no solvolytic reactions occur, allowing the development of high-yield preparation protocols for the sodium, potassium, and thallium salts and improving the yield for their derived copper boratrane complex. The photoreactivity is relevant for all future studies with electron-deficient scorpionate ligands. PMID- 26260146 TI - From Childhood Maltreatment to Allostatic Load in Adulthood: The Role of Social Support. AB - Although previous research has documented that social support acts as a protective factor for individuals exposed to trauma, most research relies on assessments of social support at one point in time. The present study used data from a prospective cohort design study to examine the stability of social support from childhood through middle adulthood in individuals with documented histories of childhood abuse and neglect and matched controls (aged 0-11) and assessed the impact of social support on allostatic load, a composite measure of physiological stress response assessed through blood tests and physical measurements, in middle adulthood. Maltreated children are more likely to have unstable social support across the life span, compared to matched controls. Social support across the life span partially mediated the relationship between child maltreatment and allostatic load in adulthood, although there were differences by race and sex. These findings have implications for interventions to prevent the negative consequences of child maltreatment. PMID- 26260145 TI - Metabolic functions of FABPs--mechanisms and therapeutic implications. AB - Intracellular and extracellular interactions with proteins enables the functional and mechanistic diversity of lipids. Fatty acid-binding proteins (FABPs) were originally described as intracellular proteins that can affect lipid fluxes, metabolism and signalling within cells. As the functions of this protein family have been further elucidated, it has become evident that they are critical mediators of metabolism and inflammatory processes, both locally and systemically, and therefore are potential therapeutic targets for immunometabolic diseases. In particular, genetic deficiency and small molecule-mediated inhibition of FABP4 (also known as aP2) and FABP5 can potently improve glucose homeostasis and reduce atherosclerosis in mouse models. Further research has shown that in addition to their intracellular roles, some FABPs are found outside the cells, and FABP4 undergoes regulated, vesicular secretion. The circulating form of FABP4 has crucial hormonal functions in systemic metabolism. In this Review we discuss the roles and regulation of both intracellular and extracellular FABP actions, highlighting new insights that might direct drug discovery efforts and opportunities for management of chronic metabolic diseases. PMID- 26260149 TI - Adult Binge Drinking: Childhood Sexual Abuse, Gender and the Role of Adolescent Alcohol-Related Experiences. AB - AIMS: This study examines gender differences in the pathway from childhood sexual abuse (CSA) to adult binge drinking. METHODS: Using longitudinal data on 313 males and females (31-41 years old, mean = 36.21) in the Lehigh Longitudinal Study, we test for gender differences in the pathway from CSA to adolescent drinking, norms and pro-alcohol peers, to adult binge drinking. RESULTS: Controlling for family history of alcohol problems, socioeconomic status (SES) and ethnicity, we found that for females there was a significant direct effect of CSA on adult binge drinking. For males there was no significant direct or indirect effect. Significant effects of family alcohol problems and SES were also moderated by gender. CONCLUSION: There are gender differences in the impact of CSA on adult binge drinking. Service providers and program developers should pay special attention to the possibility that their female clients may have a history of sexual abuse which could have implications for the course of prevention and treatment services related to binge drinking. Early intervention could prevent alcohol-related risk in adolescence which in turn could reduce, but not eliminate, the binge drinking consequences of CSA for females. PMID- 26260150 TI - Comparing measures of overall and central obesity in relation to cardiometabolic risk factors among US Hispanic/Latino adults. AB - OBJECTIVE: US Hispanics/Latinos have high prevalence of obesity and related comorbidities. We compared overall and central obesity measures in associations with cardiometabolic outcomes among US Hispanics/Latinos. METHODS: Multivariable regression assessed cross-sectional relationships of six obesity measures with cardiometabolic outcomes among 16,415 Hispanics/Latinos aged 18-74 years. RESULTS: BMI was moderately correlated with waist-to-hip ratio (WHR; women, r = 0.37; men, r = 0.58) and highly correlated with other obesity measures (r >= 0.87) (P < 0.0001). All measures of obesity were correlated with unfavorable levels of glycemic traits, blood pressure, and lipids, with similar r-estimates for each obesity measure (P < 0.05). Multivariable-adjusted prevalence ratios (PRs) for diabetes (women, 6.7 [3.9, 11.5]; men, 3.9 [2.2, 6.9]), hypertension (women, 2.4 [1.9, 3.1]; men, 2.5 [1.9, 3.4]), and dyslipidemia (women, 2.1 [1.8, 2.4]; men, 2.2 [1.9, 2.6]) were highest for individuals characterized as overweight/obese (BMI >= 25 kg/m(2)) and with abnormal WHR (women >=0.85; men, >=0.90), compared with those with normal BMI and WHR (P < 0.0001). Among normal weight individuals, abnormal WHR was associated with increased cardiometabolic condition prevalence (P < 0.05), particularly diabetes (women, PR = 4.0 [2.2, 7.1]; men, PR = 3.0 [1.6, 5.7]). CONCLUSIONS: Obesity measures were associated with cardiometabolic risk factors to a similar degree in US Hispanics/Latinos. WHR is useful to identify individuals with normal BMI at increased cardiometabolic risk. PMID- 26260151 TI - Association between vitamin D status and serum parathyroid hormone concentration and calcaneal stiffness in Japanese adolescents: sex differences in susceptibility to vitamin D deficiency. AB - There is currently insufficient information on serum 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) concentrations, and bone mineral status in healthy adolescents to allow reference values to be set. This study aimed to provide comparable data on vitamin D status in Japanese adolescents and to assess sex differences in susceptibility to vitamin D insufficiency. Serum 25OHD and PTH concentrations were measured in 1,380 healthy adolescents (aged 12-18 years). Subjects completed a questionnaire on exercise history, diet, and lifestyle factors. Calcaneal stiffness was evaluated by quantitative ultrasound. Serum 25OHD concentrations in boys and girls were 60.8 +/- 18.3 and 52.8 +/- 17.0 nmol/L, respectively. Approximately 30 % of boys and 47 % of girls had suboptimal 25OHD concentrations (<50 nmol/L). Serum PTH concentration was negatively correlated with serum 25OHD concentration in boys, but negatively correlated with calcium intake rather than serum 25OHD in girls. In contrast, the increment in calcaneal stiffness as a result of elevation of serum 25OHD was higher in girls than in boys. As vitamin D deficiency is common in Japanese adolescents, it was estimated that intakes of >=12 and >=14 MUg/day vitamin D would be required to reach 25OHD concentrations of 50 nmol/L in boys and girls, respectively. Moreover, the results of the present study indicate that vitamin D deficiency has a greater association with calcaneal stiffness in girls than in boys. PMID- 26260152 TI - Lattice Distortion in In3SbTe2 Phase Change Material with Substitutional Bi. AB - Sb atoms in In3SbTe2 (IST) are partially substituted by 3.2-5.5 at.% of Bi atoms. As a result, the NaCl crystal structure of IST is slightly distorted. The distorted inter-planar angles observed with fast Fourier transformation of the lattice images are within the maximum range of interplanar angles calculated by density functional theory. When the Bi content is increased, the crystallization temperature becomes relatively lower than that of IST, the activation energy decreases from 5.29 to 2.61 eV, and the specific heat and melting point are obviously reduced. Consequently, phase change random access memory (PRAM) fabricated with Bi-doped IST (Bi-IST) can operate with lower power consumption than pure IST PRAM. The set and reset speeds of PRAM cells fabricated with Bi-IST are both 100 ns with 5.5 at.% Bi, which are obviously faster than the switching speeds of PRAM cells fabricated with IST and Ge2Sb2Te5 (GST). These experimental results reveal that the switching speed is closely related with the thermal properties of the distorted lattice structure. PMID- 26260154 TI - Screening of young competitive athletes for the prevention of sudden cardiac death with a wireless electrocardiographic transmission device: a pilot study. AB - BACKGROUND: The 12-lead electrocardiographic screening for the prevention of sudden cardiac death in young competitive athletes is not cost-effective and thus not routinely recommended. We investigate whether a less expensive wireless electrocardiographic transmission device can be used to screen for the prevention of sudden cardiac death in this population. METHODS: During pre-participation screening, twenty college football players underwent two electrocardiograms: a conventional 12-lead electrocardiogram and a wireless 9-lead electrocardiogram. We compared several electrocardiographic parameters (QRS duration, left ventricular hypertrophy using the Cornell voltage criteria and the Sokolow-Lyon criteria, ST deviation and corrected QT interval) to determine the correlation. RESULTS: The QRS duration, left ventricular hypertrophy using the Cornell voltage criteria and the Sokolow-Lyon criteria and corrected QT interval exhibited significant correlation between the two types of electrocardiograms (correlation coefficient 0.878, 0.630, 0.770 and 0.847, respectively with P values of 0.01, 0.003, 0.01 and 0.01, respectively). ST deviation in V1 was weakly correlated between the two types of electrocardiograms without statistical significance (correlation coefficient 0.360 with a P value of 0.119). CONCLUSIONS: Our newly developed wireless 9-lead electrocardiogram demonstrated significant correlations with a conventional 12-lead electrocardiogram in terms of QRS duration, left ventricular hypertrophy and corrected QT interval. PMID- 26260153 TI - The relationship between socioeconomic indicators during pregnancy and gynecological appointment at any time after childbirth. AB - BACKGROUND: The rates of receipt of postnatal care vary widely between high and low-middle income countries. This study aimed to examine the association between indicators of socioeconomic status during pregnancy and gynecological appointment at any time after childbirth (GA). METHODS: a prospective cohort study with pregnant women recruited from 10 primary care clinics of the public sector in the city of Sao Paulo, Brazil. Socioeconomic characteristics and obstetric information were obtained through a questionnaire administered during pregnancy and in the postpartum period. Adjusted risk ratios (RR) with 95% confidence intervals (CI) were calculated using Poisson regression. RESULTS: Eight hundred and thirty one pregnant women were included in the study during the antenatal period and 701 were re-assessed during the postnatal period. Among them, 283 (59.6) attended a gynecological consultation. After adjusting for covariates, higher socioeconomic status during pregnancy was associated with greater risk of having a GA (RR:1.23, CI 95%:1.05:1.45 for family per capita monthly income; RR:1.19, CI 95 % 1.01:1.40 for asset score). CONCLUSION: In this sample, the attendance for GA was above average and women with higher socio-economic status were more likely to have receipt of such care. Special efforts should be made to improve the attendance and frequency of gynecological consultations after childbirth among poorer women. PMID- 26260155 TI - Considering the changing face of social media in higher education. AB - There is currently much ongoing consideration as to how educators can make use of new technologies to engage students. The prevalence of social media use within both private and professional circles has made these technologies increasingly important for educators. This commentary briefly outlines some of the ways social media has been used in higher education and also some of the primary concerns. Current and future trends are also addressed. PMID- 26260156 TI - Promoting microbiology education through the iGEM synthetic biology competition. AB - Synthetic biology has developed rapidly in the 21st century. It covers a range of scientific disciplines that incorporate principles from engineering to take advantage of and improve biological systems, often applied to specific problems. Methods important in this subject area include the systematic design and testing of biological systems and, here, we describe how synthetic biology projects frequently develop microbiology skills and education. Synthetic biology research has huge potential in biotechnology and medicine, which brings important ethical and moral issues to address, offering learning opportunities about the wider impact of microbiological research. Synthetic biology projects have developed into wide-ranging training and educational experiences through iGEM, the International Genetically Engineered Machines competition. Elements of the competition are judged against specific criteria and teams can win medals and prizes across several categories. Collaboration is an important element of iGEM, and all DNA constructs synthesized by iGEM teams are made available to all researchers through the Registry for Standard Biological Parts. An overview of microbiological developments in the iGEM competition is provided. This review is targeted at educators that focus on microbiology and synthetic biology, but will also be of value to undergraduate and postgraduate students with an interest in this exciting subject area. PMID- 26260157 TI - Clinical, biochemical, neuroimaging and molecular findings of X-linked Adrenoleukodystrophy patients in South China. AB - X-linked adrenoleukodystrophy is a common X-linked recessive peroxisomal disorder caused by the mutations in the ABCD1 gene. In this study, we analyzed 19 male patients and 9 female carriers with X-linked adrenoleukodystrophy in South China. By sequencing the ABCD1 gene, 13 different mutations were identified, including 7 novel mutations, and 6 known mutations, and 1 reported polymorphism. Mutation c.1180delG was demonstrated to be de novo mutation. 26.3 % (5/19) patients carried the deletion c.1415_16delAG, which may be the mutational hot spot in South China population. In addition, 73.7 % (14/19) patients were type of childhood cerebral adrenoleukodystrophy, 26.3 %(5/19) were in Addison only. Half of the childhood cerebral adrenoleukodystrophy patients had the adrenocortical insufficiency preceded the onset of neurological symptoms. Furthermore, 5 of 19 cases underwent hematopoietic stem cell transplantation. Our data showed that hematopoietic stem cell transplantation performed at an advanced stage of the cerebral X- linked adrenoleukodystrophy would accelerate the progression of the disease. Good clinical outcome achieved when hematopoietic stem cell transplantation performed at the very early stage of the disease. PMID- 26260158 TI - A qualitative study on barriers to evidence-based practice in patient counseling and advocacy in Germany. AB - BACKGROUND: Despite the attempt to integrate evidence-based practice (EBP) in patient counseling and advocacy, there is limited knowledge on the status quo of this process in the German health care system. Our objective was to identify important determinants influencing the application of EBP in the counseling and advocacy setting in Germany. METHODS: We carried out a qualitative study performing semi-structured expert interviews and one group discussion among n = 9 patient counselors (PCs) and patient advocates (PAs) identified via expert recommendations and by contacting relevant institutions. The interview manual was developed on the basis of a literature review on barriers/facilitators of EBP in health care delivery and a preamble oriented pyramid discussion with a multidisciplinary team. Interviews were analyzed using the Grounded Theory method. A paradigm was developed to present the interrelations between hindering and facilitating factors for EBP and the attitude towards the utilization of EBP among PAs and PCs. RESULTS: Findings from nine face-to-face interviews and one group discussion demonstrate that by now PCs and PAs do not recognize EBP as a tool to facilitate the professionalization of patient counselors and advocates. This result is due to individual and institutional barriers such as cognitive behavioral, professional, attitude related as well as resource and system barriers. PCs and PAs have predominantly critical attitudes towards EBP caused by a lack of trust in its reliability and by concerns regarding unfavorable effects EBP may have on the relationship with the patient and on the cooperation with physicians. A missing infrastructure of needs-based EBP training programs also discourages PCs and PAs from engaging in EBP. Despite the numerous hindering factors, there is also a growing awareness that EBP could help to improve patient counseling and advocacy. To facilitate EBP in future, needs-based training programs and health policy interventions that support interdisciplinary collaboration are required. CONCLUSION: Although EBP among PCs and PAs is gaining importance, it is still less likely to be recognized as helpful and its application faces various barriers. More needs-based EBP training programs and health policy interventions to decrease barriers and foster interdisciplinary collaboration are necessary. PMID- 26260159 TI - Moxifloxacin and ciprofloxacin induces S-phase arrest and augments apoptotic effects of cisplatin in human pancreatic cancer cells via ERK activation. AB - BACKGROUND: Pancreatic cancer, one of the most dreadful gastrointestinal tract malignancies, with the current chemotherapeutic drugs has posed a major impediment owing to poor prognosis and chemo-resistance thereby suggesting critical need for additional drugs as therapeutics in combating the situation. Fluoroquinolones have shown promising and significant anti-tumor effects on several carcinoma cell lines. METHODS: Previously, we reported growth inhibitory effects of fourth generation fluoroquinolone Gatifloxacin, while in the current study we have investigated the anti-proliferative and apoptosis-inducing mechanism of older generation fluoroquinolones Moxifloxacin and Ciprofloxacin on the pancreatic cancer cell-lines MIA PaCa-2 and Panc-1. Cytotoxicity was measured by MTT assay. Apoptosis induction was evaluated using annexin assay, cell cycle assay and activation of caspase-3, 8, 9 were measured by western blotting and enzyme activity assay. RESULTS: Herein, we found that both the fluoroquinolones suppressed the proliferation of pancreatic cancer cells by causing S-phase arrest and apoptosis. Blockade in S-phase of cell cycle was associated with decrease in the levels of p27, p21, CDK2, cyclin-A and cyclin-E. Herein we also observed triggering of extrinsic as well as intrinsic mitochondrial apoptotic pathway as suggested by the activation of caspase-8, 9, 3, and Bid respectively. All this was accompanied by downregulation of antiapoptotic protein Bcl-xL and upregulation of proapoptotic protein Bak. Our results strongly suggest the role of extracellular-signal-regulated kinases (ERK1/2), but not p53, p38 and c-JUN N terminal kinase (JNK) in fluoroquinolone induced growth inhibitory effects in both the cell lines. Additionally, we also found both the fluoroquinolones to augment the apoptotic effects of broad spectrum anticancer drug Cisplatin via ERK. CONCLUSION: The fact that these fluoroquinolones synergize the effect of cisplatin opens new insight into therapeutic index in treatment of pancreatic cancer. PMID- 26260160 TI - The Prognostic Value of Early Repolarization with ST-Segment Elevation by Age and Gender in the Hispanic Population. AB - BACKGROUND: Early repolarization (ER), once thought to be a benign finding on electrocardiograph (ECG), has recently been associated with an increased risk of sudden cardiac death. As there are limited data in the Hispanic population, we investigated possible associations between automated ECG ER readings and overall mortality, using the classic definition involving J-point elevation with ST segment elevation. METHODS: An ECG and electronic medical record (EMR) database from a regional medical center was interrogated. Inclusion criteria included Hispanic ethnicity and age over 18 from 2000 to 2011. A Cox model assessed the outcome of death. Varying morphological characteristics of ER were analyzed for high-risk features. RESULTS: There were n = 33,944 Hispanics of who n = 532 (1.6%) had ER with a mean follow-up period of 5.29 years. After adjustment for demographic, clinical, lifestyle, and laboratory variables, ER was not significantly related to all-cause mortality (hazard ratio [HR]: 1.18, 95% confidence interval [CI]: 0.90-1.54, P = 0.23). However, mortality risk of ER varied by gender and age (P interaction = 0.007). The risk of ER for mortality was highest for females (HR: 2.01, CI: 1.39-3.10, P = 0.001), with the highest overall risk for women over the age of 75 (HR: 2.09, CI: 1.12-3.92, P = 0.021) compared to women under age 75 (HR: 1.72, CI: 0.95-3.11, P = 0.075). CONCLUSIONS: ER is not associated with an increased risk of death in the overall Hispanic population. However, our analysis suggests a higher risk of overall mortality in the elderly Hispanic female population with ER. PMID- 26260161 TI - Two novel mutations in the NR5A1 gene as a cause of disorders of sex development in a Pakistani cohort of 46,XY patients. AB - NR5A1 plays a central role in gonadal development and regulation by transcriptional regulation of key modulators involved in steroidogenesis. Mutations in human NR5A1 are frequently associated with 46,XY disorders of sex development (DSD). We analysed a Pakistani cohort of patients with 46,XY DSD, presenting with variable degrees of gonadal dysgenesis, for NR5A1 mutations. The study identified three mutations (p.Tyr03X, p.Glu07X and p.Gln299HisfsX386), of which two are novel, in these patients with 46,XY DSD. The mutations, p.Tyr03X and novel p.Glu07X, are located in the coding region of the gene, corresponding to DNA-binding domain of the predicted protein. In silico analysis for the novel homozygous p.Gln299HisfsX386 mutation in ligand-binding domain of NR5A1 revealed subtle changes in overall tertiary conformation which is predicted to affect the normal physiology of this mutant protein. This study reveals two novel mutations with altered NR5A1 protein in twenty patients with 46,XY DSD, highlighting the critical role of NR5A1 protein in gonadal development and differentiation. In conclusion, the current and previous studies suggest that the NR5A1 mutations are present in around 8-15% of patients with 46,XY DSD presenting with gonadal dysgenesis. For the clinical utility of NR5A1 gene mutations, more comprehensive studies with large 46,XY DSD patient series in different populations are suggested. PMID- 26260162 TI - Breaking the computational barriers of pairwise genome comparison. AB - BACKGROUND: Conventional pairwise sequence comparison software algorithms are being used to process much larger datasets than they were originally designed for. This can result in processing bottlenecks that limit software capabilities or prevent full use of the available hardware resources. Overcoming the barriers that limit the efficient computational analysis of large biological sequence datasets by retrofitting existing algorithms or by creating new applications represents a major challenge for the bioinformatics community. RESULTS: We have developed C libraries for pairwise sequence comparison within diverse architectures, ranging from commodity systems to high performance and cloud computing environments. Exhaustive tests were performed using different datasets of closely- and distantly-related sequences that span from small viral genomes to large mammalian chromosomes. The tests demonstrated that our solution is capable of generating high quality results with a linear-time response and controlled memory consumption, being comparable or faster than the current state-of-the-art methods. CONCLUSIONS: We have addressed the problem of pairwise and all-versus all comparison of large sequences in general, greatly increasing the limits on input data size. The approach described here is based on a modular out-of-core strategy that uses secondary storage to avoid reaching memory limits during the identification of High-scoring Segment Pairs (HSPs) between the sequences under comparison. Software engineering concepts were applied to avoid intermediate result re-calculation, to minimise the performance impact of input/output (I/O) operations and to modularise the process, thus enhancing application flexibility and extendibility. Our computationally-efficient approach allows tasks such as the massive comparison of complete genomes, evolutionary event detection, the identification of conserved synteny blocks and inter-genome distance calculations to be performed more effectively. PMID- 26260163 TI - HANAC Syndrome Col4a1 Mutation Causes Neonate Glomerular Hyperpermeability and Adult Glomerulocystic Kidney Disease. AB - Hereditary angiopathy, nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is an autosomal dominant syndrome caused by mutations in COL4A1 that encodes the alpha1 chain of collagen IV, a major component of basement membranes. Patients present with cerebral small vessel disease, retinal tortuosity, muscle cramps, and kidney disease consisting of multiple renal cysts, chronic kidney failure, and sometimes hematuria. Mutations producing HANAC syndrome localize within the integrin binding site containing CB3[IV] fragment of the COL4A1 protein. To investigate the pathophysiology of HANAC syndrome, we generated mice harboring the Col4a1 p.Gly498Val mutation identified in a family with the syndrome. Col4a1 G498V mutation resulted in delayed glomerulogenesis and podocyte differentiation without reduction of nephron number, causing albuminuria and hematuria in newborns. The glomerular defects resolved within the first month, but glomerular cysts developed in 3-month-old mutant mice. Abnormal structure of Bowman's capsule was associated with metalloproteinase induction and activation of the glomerular parietal epithelial cells that abnormally expressed CD44,alpha-SMA, ILK, and DDR1. Inflammatory infiltrates were observed around glomeruli and arterioles. Homozygous Col4a1 G498V mutant mice additionally showed dysmorphic papillae and urinary concentration defects. These results reveal a developmental role for the alpha1alpha1alpha2 collagen IV molecule in the embryonic glomerular basement membrane, affecting podocyte differentiation. The observed association between molecular alteration of the collagenous network in Bowman's capsule of the mature kidney and activation of parietal epithelial cells, matrix remodeling, and inflammation may account for glomerular cyst development and CKD in patients with COL4A1-related disorders. PMID- 26260164 TI - A Quantitative Approach to Screen for Nephrotoxic Compounds In Vitro. AB - Nephrotoxicity due to drugs and environmental chemicals accounts for significant patient mortality and morbidity, but there is no high throughput in vitro method for predictive nephrotoxicity assessment. We show that primary human proximal tubular epithelial cells (HPTECs) possess characteristics of differentiated epithelial cells rendering them desirable to use in such in vitro systems. To identify a reliable biomarker of nephrotoxicity, we conducted multiplexed gene expression profiling of HPTECs after exposure to six different concentrations of nine human nephrotoxicants. Only overexpression of the gene encoding heme oxygenase-1 (HO-1) significantly correlated with increasing dose for six of the compounds, and significant HO-1 protein deregulation was confirmed with each of the nine nephrotoxicants. Translatability of HO-1 increase across species and platforms was demonstrated by computationally mining two large rat toxicogenomic databases for kidney tubular toxicity and by observing a significant increase in HO-1 after toxicity using an ex vivo three-dimensional microphysiologic system (kidney-on-a-chip). The predictive potential of HO-1 was tested using an additional panel of 39 mechanistically distinct nephrotoxic compounds. Although HO-1 performed better (area under the curve receiver-operator characteristic curve [AUC-ROC]=0.89) than traditional endpoints of cell viability (AUC-ROC for ATP=0.78; AUC-ROC for cell count=0.88), the combination of HO-1 and cell count further improved the predictive ability (AUC-ROC=0.92). We also developed and optimized a homogenous time-resolved fluorescence assay to allow high throughput quantitative screening of nephrotoxic compounds using HO-1 as a sensitive biomarker. This cell-based approach may facilitate rapid assessment of potential nephrotoxic therapeutics and environmental chemicals. PMID- 26260166 TI - Socio-ecological features other than sex affect habitat selection in the socially obligate monogamous Eurasian beaver. AB - Habitat selection is a context-dependent mechanism, in which both the internal state as well as external factors affect the behavior and decisions of an individual. This is well known for polygamous mammals, which are typically sexually dimorphic, and often express great variability in behavior and habitat selection between individuals as well between the sexes. Among monogamous mammals, however, variability in habitat selection should be explained by group characteristics and the presence of offspring rather than by sex. We evaluated this hypothesis in a socially monogamous rodent, the Eurasian beaver (Castor fiber), in a saturated Norwegian population. For the first time in this species we applied GPS tracking devices (N = 22 adult beavers, in 15 territories, 2009 2013), and used resource selection functions (i) to document population-wide habitat selection and the importance of 'territory' therein, and (ii) to evaluate which socio-ecological factors explained potential individual differences in habitat selection. We found that variation in habitat selection was stronger between territories than between years or individuals nested by territory. We identified that family size and the presence of kits, but not sex, explained individual variation in habitat selection. Adults with kits and/or larger families tended to exhibit low risk-taking behavior (avoiding human-related variables such as roads, buildings, and agricultural land), and stayed close to their main lodge (parental care). Our results show that habitat selection is a context-dependent mechanism even in a species which expresses very little behavioral and morphological dimorphism. PMID- 26260167 TI - A quantitative analysis of phenotypic variations of Metrosideros polymorpha within and across populations along environmental gradients on Mauna Loa, Hawaii. AB - Metrosideros polymorpha, a dominant tree species in the Hawaiian Islands, shows an extreme phenotypic polymorphism both across gradients of climatic/edaphic conditions and within populations, making it a potentially useful model species for evolutionary study. In order to understand how the phenotypic diversity is maintained within populations as well as across populations, we examined the diversities of several leaf and stem functional traits across five elevations and two soil substrates on the volcanic mountain of Mauna Loa, on the island of Hawaii. Leaf dry mass per area (LMA), a key leaf functional trait, was particularly focused on and analyzed in relation to its underlying components namely, tissue LMA and trichome LMA (LMA = tissue LMA + trichome LMA). Across populations, tissue LMA increased linearly with elevation while trichome LMA showed unimodal patterns with elevation, which were better correlated with temperature and rainfall, respectively. Substantial phenotypic variations were also found within populations. Interestingly, the variations of tissue LMA were often negatively correlated to trichome LMA within populations, which contrasts with the cross-populations pattern, where a strong positive correlation between tissue LMA and trichome LMA was found. This suggests that phenotypic variations within populations were substantially influenced by local ecological processes. Soil depth (an indicator of local water availability) and tree size (an indicator of colonized timing) modestly explained the within-population variations, implying other local environmental factors and/or random processes are also important in local phenotypic diversity. This study provides an insight about how phenotypic diversity of plant species is maintained from local to landscape levels. PMID- 26260168 TI - Clinical and genetic features of human metapneumovirus infection in children. AB - BACKGROUND: Human metapneumovirus (hMPV) is one of the main pathogens responsible for respiratory tract infection in children. METHODS: From 2011 to 2013, nasopharyngeal aspirates were obtained from Korean children and tested for hMPV on reverse transcription-polymerase chain reaction (RT-PCR). The genotype of hMPV in each sample was identified on PCR-restriction length polymorphism analysis of the fusion gene. We divided patients into three groups according to degree of fever. Patients with fever peaking at >39.5 degrees C or lasting >7 days were classified as the high fever (HF) group; those with fevers peaking at <38.5 degrees C and lasting <72 h were classified as the low fever (LF) group; and the other subjects were classified as the moderate fever group. RESULTS: Among 457 samples positive for hMPV, hMPV genotype was able to be identified in 399 (87.3%); of these, A2a was found in 97 (24.3%), B1 in 186 (46.6%), and B2 in 116 (29.1%). Clinical features of hMPV infection were compared between the HF and LF groups. We classified 80 subjects into the HF group and 84 subjects into the LF group. Mean absolute neutrophil count (5625 +/- 4418 vs 4072 +/- 3076/MUL, P = 0.010) and C-reactive protein (2.39 +/- 3.39 vs 0.96 +/- 1.77 mg/dL, P = 0.001) were higher in the HF group. Wheezing (5.0% vs 32.1%, P < 0.001) and dyspnea (2.5% vs 15.5%, P = 0.010) were more frequently seen in the LF group. Genotype distribution was similar in the two groups. CONCLUSION: Two distinct clinical presentations of hMPV infection were identified in this study. PMID- 26260169 TI - Basal autophagy is negatively regulated by RIP1. PMID- 26260165 TI - Spectrum and Prognosis of Noninfectious Renal Mixed Cryoglobulinemic GN. AB - Noninfectious mixed cryoglobulinemic GN (MCGN) has been poorly investigated. We analyzed presentation and outcome of 80 patients with biopsy-proven MCGN, which were identified in the retrospective French CryoVas survey. MCGN was related to primary Sjogren's syndrome in 22.5% of patients and to lymphoproliferative disorders in 28.7% of patients, and was defined as essential in 48.8% of patients. At presentation, hematuria, proteinuria >=1 g/d, hypertension, and renal failure were observed in 97.4%, 84.8%, 85.3%, and 82.3% of cases, respectively. Mean+/-eGFR was 39.5+/-20.4 ml/min per 1.73 m(2) Membranoproliferative GN was the predominant histologic pattern, observed in 89.6% of cases. Renal interstitium inflammatory infiltrates were observed in 50% of cases. First-line treatment consisted of steroids alone (27.6%) or in association with rituximab (21.1%), alkylating agents (36.8%) or a combination of cyclophosphamide and rituximab (10.5%). After a mean follow-up of 49.9+/-45.5 months, 42.7% of patients relapsed with a renal flare in 75% of cases. At last follow-up, mean eGFR was 50.2+/-26.1 ml/min per 1.73 m(2)with 9% of patients having reached ESRD; 59% and 50% of patients achieved complete clinical and renal remission, respectively. A rituximab+steroids regimen prevented relapses more effectively than steroids alone or a cyclophosphamide+steroids combination did, but was associated with a higher rate of early death when used as first-line therapy. Severe infections and new-onset B-cell lymphoma occurred in 29.1% and 8.9% of cases, respectively; 24% of patients died. In conclusion, noninfectious MCGN has a poor long-term outcome with severe infections as the main cause of death. PMID- 26260170 TI - Complete mitochondrial genome of the American flamingo, Phoenicopterus ruber (Phoenicopteriformes, Phoenicopteridae). AB - The American flamingo, Phoenicopterus ruber (P. ruber), is a large species of flamingo closely related to the greater flamingo and Chilean flamingo. In this paper, the complete mitochondrial genome sequence of P. ruber has been assembled for the first time. It was 17 476 bp in length and consisted of 13 typical vertebrate protein-coding genes, 22 tRNA genes, 2 rRNA genes and 2 control regions. COI and ND3 genes used GTG and ATC as start codons respectively, but the remaining protein-coding genes were encoded beginning with orthodox ATG codon. Two triplet codons (TAA, AGG) and one single T base were employed as stop codons. The arrangement of the overall genes and noncoding regions was identical to the same genus flamingo Phoenicopterus roseus. The AT content (54.27%) was higher than the GC content. Phylogenetic analysis was performed using 12 protein-coding genes, combined with other 11 species from the same Neognathae, which validated the responsibility and utility of this new mitochondrial genome. PMID- 26260171 TI - The phylogenetic position of the giant devil ray Mobula mobular (Bonnaterre, 1788) (Myliobatiformes, Myliobatidae) inferred from the mitochondrial genome. AB - The giant devil ray, Mobula mobular, is a member of one of the most distinct groups of cartilaginous fishes, the Mobulidae (manta and devil rays), and is the only mobulid assessed as Endangered due its restricted distribution, high bycatch mortality and suspected population decline. The complete mitochondrial genome is 18 913 base pairs in length and comprises 2 rRNAs, 13 protein-coding genes, 22 tRNAs and 2 non-coding regions. Comparison with the partial mitogenome of M. japanica suggests a sister-cryptic species complex and two different taxonomic units. However, the limited divergence within the species (>99.9% genetic identity) may be the result of a geographically and numerically restricted population of M. mobular within the Mediterranean Sea. PMID- 26260172 TI - Complete mitochondrial genome of the Korean endemic species Microphysogobio yaluensis (Teleostei, Cypriniformes, Cyprinidae). AB - In this study, we sequenced the complete mitochondrial genome of the Korean endemic species Microphysogobio yaluensis (Teleostei, Cypriniformes, Cyprinidae). The mitogenome, consisted of 16 601 base pairs (bp), encoding 13 protein-coding genes (PCGs), 2 ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs) and 2 non-coding regions. The overall base composition of M. yaluensis was G + C: 43.8%, A + T: 56.2%, apparently with a slight AT bias. Phylogenetic analysis showed that M. yaluensis was close to Hemibarbus mylodon. PMID- 26260173 TI - The complete mitochondrial genome of Chinese land snail Aegista aubryana (Gastropoda: Pulmonata: Bradybaenidae). AB - Aegista aubryana is an endemic land snail in China. The complete mitochondrial genome of A. aubryana was first determined using long PCR reactions and primer walking method (accession number KT192071). The genome has a length of 14 238 bp, containing 37 typical mitochondrial genes (13 protein-coding genes, 22 tRNA genes and 2 rRNA genes). The base composition of the whole heavy strand is A 31.32%, T 37.86%, C 14.46% and G 16.36%. The results of phylogenetic analyses showed that the A. aubryana is most closely related to Mastigeulota kiangsinensis. This new complete mitochondrial genome can be the basic data for further studies on mitogenome comparison, molecular taxonomy and phylogenetic analyses in bradybaenid snails and Molluscs at large. PMID- 26260174 TI - Intraspecific mitochondrial variations between Rhinogobio typus from the Yellow River and Yangtze River. AB - The complete mitochondrial genome of the first individual Rhinogobio typus collected from the Yellow River were sequenced and compared with the previously reported complete mitochondrial sequence of Rhinogobio typus from the Yangtze River. The length of their circular mitochondrial genome was determined to be 16 599 and 16 608 bp respectively. The comparison of two mitochondrial genomes revealed 237 base pair substitutions and 17 insertions or deletions (indels), including 182 base pair substitutions and 2 indels in protein-coding region. Phylogenetic tree was constructed based on complete mitogenomes of the two populations and closely related 13 teleost species to assess their phylogenic relationship and evolution. PMID- 26260175 TI - Complete mitochondrial genome of the soft-shell clam Mya arenaria. AB - We have sequenced and characterized the complete mitochondrial genome of the soft shell clam, Mya arenaria, an important organism for environmental toxicology and aquaculture. Mya arenaria is located in the taxonomic order Myoida, which lacks any member with a completely annotated mitogenome. The M. arenaria mitochondrial genome is 17 947 bp in length. Like most marine bivalves, the circular mitogenome codes entirely on the heavy strand, with no introns. As with other bivalves, the gene order of the mitochondrion is highly rearranged. The mitogenome contains 12 protein-coding genes but ATP8 is missing, consistent with about half of all bivalve genera. Twenty-three tRNAs were identified. Phylogenetic analysis shows that M. arenaria is related most closely with the bivalves Sinonovacula constricta, and Moerella iridescens, of the infraclass Euheterodonta (unassigned). This, along with the close grouping of the phylogenetic trees, confirms a close tie between Myoida and Euheterodonta (unassigned). PMID- 26260176 TI - Complete mitochondrial genome of Parastichopus californicus (Aspidochirotida: Stichopodidae). AB - In this study, we first determined and described the complete mitogenome sequence of Parastichopus californicus, which was 16 727 bp in length. The mitochondrial genome had the canonical mitochondrial gene content, including 13 protein-coding genes, 2 rRNA genes and 22 tRNA genes. The overall base composition of the heavy strand was 31.5% A, 18 % G, 20.6% C and 29.9% T, with a high A + T content of 61.4%. ML phylogenetic tree indicated that P. californicus and P. nigripunctatus were clustered in one branch belonging to the genus Parastichopus. This conclusion was identical to the former result by the methods of morphological taxonomy. PMID- 26260177 TI - The complete mitochondrial genome and phylogenic analysis of Pseudobagrus vachelli. AB - The complete mitochondrial genome of Pseudobagrus vachelli has been sequenced. The mitochondrial genome is 16 529 bp in length, with the base composition of 31.61% A, 26.88% T, 26.55% C, and 14.96% G, containing 2 ribosomal RNA genes, 13 protein-coding genes, 22 transfer RNA genes and a major non-coding control region (D-loop region). The gene order and orientation are similar with some typical fish species. The data will provide useful molecular information for phylogenetic studies concerning P. vachelli and its related species. PMID- 26260178 TI - The complete mitochondrial genome of the Pundamilia nyererei (Perciformes, Cichlidae). AB - Pundamilia nyererei (Perciformes, Cichlidae) is a member of Cichlid fishes that lives in the Great Lakes of East Africa. Fishes of the Cichlidae family can adapt spectacular trophic radiations and provide good potential examples of vertebrate adaptive radiations. Here, we firstly assembled the complete mitochondrial genome (mitogenome) of Pundamilia nyererei. The mitgenome was 16 761 bp in length, including 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and 1 putative control region. Most of these protein-coding genes started with a traditional ATG codon except for COX1, which initiated with an infrequent start codon GTG instead, and terminated with the mitochondrial stop codon (TAA/AGG/AGA) or a single T base. The mitogenome structural organization is identical to other Cichlid fish. The overall GC content is 45.25%, which is lower than the AT content. According to these new determined mitogenome sequences and 10 other species under the same family or order, we have constructed the species phylogenetic tree to verify the accuracy of newly assembled mitogenome sequences. We accept that by taking the advantage of full mitogenome, we can address taxonomic issue and study the related evolutionary events. Our current data are going to provide important resources for the research of Cichlid fishes mitochondrial evolution and energy metabolism. PMID- 26260179 TI - Complete mitochondrial genome sequence of Chestnut-flanked white-eye (Zosterops erythropleurus). AB - The Chestnut-flanked white-eye (Zosterops erythropleurus) is a species of family Zosteropidae, which is distributed widely in the world. In the present study, the complete mitochondrial genome sequence of Chestnut-flanked white-eye was determined. It has a total length of 17 811 bp, and contains 13 protein-coding genes, 22 tRNA genes, 2 ribosome RNA genes and 2 control regions. The total base composition was 30.2% for A, 31.0% for C, 14.2% for G and 24.6% for T. The phylogenetic tree of Chestnut-flanked white-eye and 13 other species belonging to the order Passeriformes was built. The molecular data presented here will be useful to study the evolutionary relationships and genetic diversity of Chestnut flanked white-eye. PMID- 26260180 TI - The complete plastid genome of Piper kadsura (Piperaceae), an East Asian woody vine. AB - We sequenced the complete plastid genome (plastome) for Piper kadsura, a woody vine endemic to East Asia. This species is part of the largest genus within Piperaceae and its genome is almost identical to its congener P. cenocladum. The plastome for P. kadsura comprises 131 genes, including four unique rRNAs, 30 tRNAs, and 79 protein-coding genes. It retains ycf1 as an intact open reading frame. Our phylogenetic analysis demonstrated the monophyly of the Piper genus. The additional plastome sequence found in this evolutionarily and economically important genus will be a valuable, fundamental tool for future studies of phylogenetic relationships among basal angiosperms, and will provide a useful resource for molecular breeding programs. PMID- 26260181 TI - The complete chloroplast genome of Schrenkiella parvula (Brassicaceae). AB - Schrenkiella parvula is an Arabidopsis-related model species used here for studying plant stress tolerance. In this study, the complete chloroplast genome sequence of S. parvula has been reported for the first time. The total length of the chloroplast genome was 153 979 bp, which had a typical quadripartite structure. The annotated plastid genome includes 87 protein-coding genes, 39 tRNA genes and 8 ribosomal RNA genes. The evolutionary relationships revealed by our phylogenetic analysis indicated that S. parvula is closer to the Brassiceae species when compared with Eutrema salsugineum. PMID- 26260182 TI - Genetic diversity and relationship of Mauremys mutica and M. annamensis assessed by DNA barcoding sequences. AB - The mitochondrial DNA cytochrome c oxidase subunit I gene (COI) has been used as an efficient barcoding tool for species identification of animals. In this study, the barcoding sequences were used to assess the genetic diversity and relationship of Mauremy mutica and M. annamensis. Four currently recognized groups of M. mutica were classified into two groups in this study, with 6% intergroup distances, the S group and the N group, consistent to the calling of "southern turtle" and "northern turtle" in folk of China. The north population and Taiwan population formed the N group, and further, the Taiwan population was differentiated as a monophyly originated from the north population, consistent to the calling of "big green head" for the Taiwan population and "small green head" for the north population. The Vietnam, Hainan population, and M. annamensis formed the S group, and the barcoding sequences could not distinguish them from each other. Based on the molecular data and phenotypes of existing hybrids, hybrid origin of M. annamensis may be another possibility. PMID- 26260183 TI - The complete chloroplast genome sequence of Zanthoxylum piperitum. AB - The complete chloroplast genome sequence of Zanthoxylum piperitum, a plant species with useful aromatic oils in family Rutaceae, was generated in this study by de novo assembly with whole-genome sequence data. The chloroplast genome was 158 154 bp in length with a typical quadripartite structure containing a pair of inverted repeats of 27 644 bp, separated by large single copy and small single copy of 85 340 bp and 17 526 bp, respectively. The chloroplast genome harbored 112 genes consisting of 78 protein-coding genes 30 tRNA genes and 4 rRNA genes. Phylogenetic analysis of the complete chloroplast genome sequences with those of known relatives revealed that Z. piperitum is most closely related to the Citrus species. PMID- 26260184 TI - Low-depth shotgun sequencing resolves complete mitochondrial genome sequence of Labeo rohita. AB - Labeo rohita, popularly known as rohu, is a widely cultured species in whole Indian subcontinent. In the present study, we used in-silico approach to resolve complete mitochondrial genome of rohu. Low-depth shotgun sequencing using Roche 454 GS FLX (Branford, Connecticut, USA) followed by de novo assembly in CLC Genomics Workbench version 7.0.4 (Aarhus, Denmark) revealed the complete mitogenome of L. rohita to be 16 606 bp long (accession No. KR185963). It comprised of 13 protein-coding genes, 22 tRNAs, 2 rRNAs and 1 putative control region. The gene order and organization are similar to most vertebrates. The mitogenome in the present investigation has 99% similarity with that of previously reported mitogenomes of rohu and this is also evident from the phylogenetic study using maximum-likelihood (ML) tree method. This study was done to determine the feasibility, accuracy and reliability of low-depth sequence data obtained from NGS platform as compared to the Sanger sequencing. Thus, NGS technology has proven to be competent and a rapid in-silico alternative to resolve the complete mitochondrial genome sequence, thereby reducing labors and time. PMID- 26260185 TI - The complete mitochondrial genome of the Poecilia formosa (Amazon molly). AB - The Amazon molly, Poecilia formosa, a member of the Poeciliidae family, is a freshwater fish reproducing through gynogenesis. The complete mitochondrial genome of the P. formosa is determined for the first time in this study. It is a circular molecule of 16 542 bp in length, including 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and 1 putative control region. The overall base composition of the genome is A (29.59%), T (27.57%), C (28.27%), and G (14.57%) with 42.84% GC content, which is lower than the content of AT. Most protein-coding genes started with a traditional ATG codon except for COX2, ND5 and ND6, which initiated with ATA, GTG and TTA, respectively. The stop codon was a single T- - base in most of the protein-coding genes, but COX2 and ATP8 both employed TAA and ND2 terminated with AGG codon. Phylogenetic tree was constructed based on the complete mitogenome of P. formosa and closely related 11 chondrichthian species to assess their phylogenic relationship and evolution. The complete mitochondrial genome of the amazon molly would help to study the evolution of Poeciliidae family. PMID- 26260187 TI - Intramolecular Cyclization of Carbonate and Thiocarbonate Derivatives of myo Inositol in the Solid State: Implications for Acyl Group Transfer Reactions in Molecular Crystals. AB - Racemic 4-O-phenoxycarbonyl and 4-O-phenoxythiocarbonyl derivatives of myo inositol orthoformate undergo thermal intramolecular cyclization in the solid state to yield the corresponding 4,6-bridged carbonates and thiocarbonates, respectively. The thermal cyclization also occurs in the solution and molten states, but less efficiently, suggesting that these cyclization reactions are aided by molecular pre-organization, although not strictly topochemically controlled. Crystal structures of two carbonates and a thiocarbonate clearly revealed that the relative orientation of the electrophile and the nucleophile in the crystal lattice facilitates the intramolecular cyclization reaction and forbids the intermolecular reaction. The correlation observed between the chemical reactivity and the non-covalent interactions in the crystal of the reactants provides a way to estimate the chemical stability of analogous molecules in the solid state. PMID- 26260186 TI - Complete mitochondrial genome of Schizothorax nukiangensis Tsao (Cyprinidae: Schizothorax). AB - In this work, we reported the complete mitochondrial genome sequence of the Schizothorax nukiangensis Tsao for the first time. The complete mtDNA genome sequence of S. nukiangensis Tsao was 16 585 bp in length, which contains 22 transfer RNA genes, 2 rRNA genes, 13 protein-coding genes, an origin of light strand replication (OL) and a control region (D-Loop). The overall base composition of the mitogenome was calculated to be 29.6% for A, 27.0% for C, 17.9% for G and 25.5% for T. The complete mitogenome of the S. nukiangensis Tsao can provide an important data set for further studies on population history, molecular systematics, phylogeography and stock assessment. PMID- 26260188 TI - Assessment of personal occupational radiation exposures received by nuclear medicine and oncology staff in Punjab (2003-2012). AB - The impact of occupational radiation exposures on oncology staff working in the disciplines of Nuclear Medicine (NM), Radiotherapy (RT), and Diagnostic Radiology (DR) is of significance to ensure a health risk free environment. In this study, occupationally received radiation doses amongst Pakistani oncology staff in NM, RT and DR during the period (2003-2012) were assessed. The Film Badge Dosimetry (FBD) technique has been utilized to process over 81,000 films (13,237 workers) concerning the occupationally exposed workers data (2003-2012) at a national scale. The annual effective doses were found to range between 0.30-0.97 mSv for NM, 0.44-1.02 mSv for RT and 0.31-1.09 mSv for DR. The annual effective doses averaged over a period of 10 years were assessed to be 0.63, 0.70 and 0.68 mSv for NM, RT and DR respectively. The exposure data were categorized into three exposure levels (<=0.99, 1-4.99 and 5-9.99 mSv) to establish the staff distribution in these categories. It was found that 89.8-96% in NM, 82-94.5% in RT and 76-96.8% staff workers in DR have received doses within the range from the Minimum Detectable Limit (MDL)--0.99 mSv. The annual effective doses, in all categories, were measured to be less than the recommended annual limit of 20 mSv. PMID- 26260189 TI - Decline of lymphatic vessel density and function in murine skin during aging. AB - Lymphatic vessels play important roles in the pathogenesis of many conditions that have an increased prevalence in the elderly population. However, the effects of the aging process on the lymphatic system are still relatively unknown. We have applied non-invasive imaging and whole-mount staining techniques to assess the lymphatic vessel function and morphology in three different age groups of mice: 2 months (young), 7 months (middle-aged), and 18 months (aged). We first developed and validated a new method to quantify lymphatic clearance from mouse ear skin, using a lymphatic-specific near-infrared tracer. Using this method, we found that there is a prominent decrease in lymphatic vessel function during aging since the lymphatic clearance was significantly delayed in aged mice. This loss of function correlated with a decreased lymphatic vessel density and a reduced lymphatic network complexity in the skin of aged mice as compared to younger controls. The blood vascular leakage in the skin was slightly increased in the aged mice, indicating that the decreased lymphatic function was not caused by a reduced capillary filtration in aged skin. The decreased function of lymphatic vessels with aging might have implications for the pathogenesis of a number of aging-related diseases. PMID- 26260190 TI - An intravascular coronary plaque elasticity reconstruction method using limited depth penetration ultrasound signals. PMID- 26260191 TI - Biofilm formation ability of Salmonella enterica serovar Typhimurium acrAB mutants. AB - Recent studies offer contradictory findings about the role of multidrug efflux pumps in bacterial biofilm development. Thus, the aim of this study was to investigate the involvement of the AcrAB efflux pump in biofilm formation by investigating the ability of AcrB and AcrAB null mutants of Salmonella enterica serovar Typhimurium to produce biofilms. Three models were used to compare the ability of S. Typhimurium wild-type and its mutants to form biofilms: formation of biofilm on polystyrene surfaces; production of biofilm (mat model) on the air/liquid interface; and expression of curli and cellulose on Congo red supplemented agar plates. All three investigated genotypes formed biofilms with similar characteristics. However, upon exposure to chloramphenicol, formation of biofilms on solid surfaces as well as the production of curli were either reduced or were delayed more significantly in both mutants, whilst there was no visible effect on pellicle formation. It can be concluded that when no selective pressure is applied, S. Typhimurium is able to produce biofilms even when the AcrAB efflux pumps are inactivated, implying that the use of efflux pump inhibitors to prevent biofilm formation is not a general solution and that combined treatments might be more efficient. Other factors that affect the ability to produce biofilms depending on efflux pump activity are yet to be identified. PMID- 26260192 TI - Single-dose pharmacokinetics of vancomycin in porcine cancellous and cortical bone determined by microdialysis. AB - High treatment failure rates and the need for prolonged antimicrobial therapy for osteomyelitis and implant-associated infections suggest that antimicrobial bone penetration may be incomplete. Assessment of the bone pharmacokinetics of antimicrobials is challenged by a lack of validated methods. In this study, 1000 mg of vancomycin was administered as a single dose over 100 min to eight female pigs. Plasma, subcutaneous adipose tissue (SCAT) and bone pharmacokinetics were investigated over 12 h. Microdialysis was applied for collection of samples in bone and SCAT. The vancomycin concentration in microdialysates was determined using ultra-high performance liquid chromatography, whilst the free plasma concentration was determined using Cobas c501. The mean (95% CI) area under the concentration-time curve (AUC(0-last); minMUg/mL) was 9375 (7445-11304), 9304 (7374-11233), 5998 (3955-8040) and 3451 (1522-5381) for plasma, SCAT, and cancellous and cortical bone, respectively (ANOVA P-value < 0.001). Both cortical and cancellous bone AUC0-last were lower than that of free plasma (P < 0.01). Peak drug concentrations (C(max)) in cortical and cancellous bone were also significantly lower than that of free plasma (P < 0.001). Moreover, both AUC(0 last) and C(max) were significantly lower in cortical bone than in cancellous bone (P < 0.025). Bone penetration of vancomycin was found to be incomplete and delayed. Significant differences in pharmacokinetics between cancellous and cortical bone suggest that bone may not be considered as one compartment. Future studies should focus on validating the applicability of microdialysis for assessment of antimicrobial bone pharmacokinetics. PMID- 26260193 TI - Prognostic value of computed tomography before radical cystectomy in patients with invasive bladder cancer: imaging predicts survival. AB - PURPOSE: Computed tomography (CT) is current standard-of-care for preoperative staging in patients with invasive bladder cancer before radical cystectomy (RC). There are only sparse data on the association between preoperative CT findings and postoperative survival of patients. METHODS: We retrospectively evaluated preoperative CTs of 206 patients with invasive bladder cancer undergoing RC in an academic tertiary referral center. CTs were analyzed retrospectively for relative bladder wall thickness (BWT) and size of lymph nodes (LN). Associations between CT findings and risk of death from any cause (AC) as well as risk of death from bladder cancer (BC) were assessed by Kaplan-Meier estimates, cumulative incidence curves and multivariable Cox regression analysis. RESULTS: The median follow-up was 40 months. Increased BWT was significantly correlated with higher risk of death (AC: HR 1.68; p = 0.043; BC: HR 2.00; p = 0.027), as well as LN with a size of 6-10 mm (AC: HR 2.13; p = 0.002; BC: HR 2.77; p = 0.002) and >10 mm (AC: HR 2.47; p = 0.018; BC: HR 3.66; p = 0.007) when compared to LN <= 5 mm. CONCLUSION: Our data showed a significant correlation of bladder wall thickness and LN size with the risk of death. Also lymph nodes >5 mm but <= 10 mm (resp. <= 8 mm) usually considered non-pathologic-were associated with a significantly worse prognosis. This information can be used to counsel patients preoperatively. It might also be useful for a risk-adapted approach in regard to neoadjuvant chemotherapy. PMID- 26260194 TI - High-risk human papillomavirus and cervical lesions among women living with HIV/AIDS in Brazilian Amazon, Brazil. AB - OBJECTIVE: The goal of this study was to determine the prevalence of human papillomavirus infection infection and cervical lesions and its associated factors among HIV infected women attending an AIDS clinic in Amazonas state, Brazil. METHODS: Cross-sectional study. Women attending an AIDS clinic in the city of Manaus between March and December 2011 for gynecological examination were invited to participate. Enrolled patients answered a standardized interview including demographical, behavioral, and clinical data. Additionally, patients underwent a gynecological evaluation with collection of cervical samples for cytological analysis and high-risk human papillomavirus infection hybrid capture. A blood sample was also obtained to determine CD4 and viral load levels. RESULTS: A total of 310 (82.9%) women participated in the study. High-risk human papillomavirus infection was detected in 191 (61.6%) cases; 24 (13.5%) had low grade squamous intraepithelial lesion (SIL) and 4 (2.2%) high-grade SIL. No invasive cervical cancer was diagnosed. Median age was 32 (interquartile range (IQR): 27-38) years and median of education was 8.5 (IQR 4-11) years of schooling and 56.1% had a monthly income up to US$180. In multivariate analysis, being less than 30 years old [OR=1.7 (95% CI: 1.2-2.4, p=0.005)], high-grade SIL [OR=6.5 (95% CI: 1.6-23.0, p=0.009)], and CD4 counts <200cells/mm(3) [OR=1.6 (95% CI: 1.2 2.0, p<0.001)] were associated with high risk human papillomavirus infection infection. CONCLUSIONS: In the present study high-risk human papillomavirus infection was frequent and it was associated to high-SIL. These results show the importance of gynecologic examinations in routine care and follow-up required by those who present with cervical lesions. PMID- 26260195 TI - Enhanced plasmid DNA utilization in transiently transfected CHO-DG44 cells in the presence of polar solvents. AB - Although the protein yields from transient gene expression (TGE) with Chinese hamster ovary (CHO) cells have recently improved, the amount of plasmid DNA (pDNA) needed for transfection remains relatively high. We describe a strategy to reduce the pDNA amount by transfecting CHO-DG44 cells with 0.06 MUg pDNA/10(6) cells (10% of the optimal amount) in the presence of nonspecific (filler) DNA and various polar solvents including dimethylsufoxide, dimethyl formamide, acetonitrile, dimethyl acetamide (DMA), and hexamethyl phosphoramide (HMP). All of the polar solvents with the exception of HMP increased the production of a recombinant antibody in comparison to the untreated control transfection. In the presence of 0.25% DMA, the antibody yield in a 7-day batch culture was 500 mg/L. This was fourfold higher than the yield from the untreated control transfection. Mechanistic studies revealed that the polar solvents did not affect polyethylenimine-mediated pDNA delivery into cells or nuclei. The steady-state transgene mRNA level was elevated in the presence of each of the polar solvents tested, while the transgene mRNA half-life remained the same. These results indicated that the polar solvents enhanced transgene transcription. When screening a panel of recombinant antibodies and Fc-fusion proteins for production in the presence of the polar solvents, the highest increase in yield was observed following DMA addition for 11 of the 12 proteins. These results are expected to enhance the applicability of high-yielding TGE processes with CHO-DG44 cells by decreasing the amount of pDNA required for transfection. PMID- 26260196 TI - [Short version S2e guidelines: "Positioning therapy and early mobilization for prophylaxis or therapy of pulmonary function disorders"]. AB - The German Society of Anesthesiology and Intensive Care Medicine (DGAI) commissioned a revision of the S2 guidelines on "positioning therapy for prophylaxis or therapy of pulmonary function disorders" from 2008. Because of the increasing clinical and scientific relevance the guidelines were extended to include the issue of "early mobilization" and the following main topics are therefore included: use of positioning therapy and early mobilization for prophylaxis and therapy of pulmonary function disorders, undesired effects and complications of positioning therapy and early mobilization as well as practical aspects of the use of positioning therapy and early mobilization. These guidelines are the result of a systematic literature search and the subsequent critical evaluation of the evidence with scientific methods. The methodological approach for the process of development of the guidelines followed the requirements of evidence-based medicine, as defined as the standard by the Association of the Scientific Medical Societies in Germany. Recently published articles after 2005 were examined with respect to positioning therapy and the recently accepted aspect of early mobilization incorporates all literature published up to June 2014. PMID- 26260197 TI - [Perioperative treatment of patients with long QT syndrome]. AB - Long QT syndrome (LQTS) is caused by a change in cardiac repolarization due to functional ion channel dysfunction which is associated with an elongation of the QT interval (hence the name) in the electrocardiogram and a predisposition to cardiac rhythm disorders (e.g. torsade de pointes, TdP) as well as cardiac events up to sudden cardiac death. There is a congenital (cLQTS) and an acquired (aLQTS) form of the disease. The prevalence of cLQTS is 1 in 2000 but aLQTS is much more common and includes a grey area due to many asymptomatic patients. The LQTS is, therefore, more common than malignant hyperthermia which is much discussed in anesthesiology and has a reported prevalence in the population of 1:3000. Considering the prevalence of both aLQTS as well as cLQTS the importance of the LQTS seems to be underestimated in current perioperative care. Potential perioperative risks of such patients can be significantly reduced by appropriate patient management. This includes adequate preoperative preparation, the correct choice of anesthetic medication as well as adequate perioperative monitoring and preparedness for immediate pharmaceutical and electrical intervention in case of typical cardiac rhythm disturbances, such as TdP arrhythmia. PMID- 26260198 TI - Pluripotent Stem Cells and Skeletal Regeneration--Promise and Potential. AB - The bone is a regenerative tissue, capable of healing itself after fractures. However, some circumstances such as critical-size defects, malformations, and tumor destruction may exceed the skeleton's capacity for self-repair. In addition, bone mass and strength decline with age, leading to an increase in fragility fractures. Therefore, the ability to generate large numbers of patient specific osteoblasts would have enormous clinical implications for the treatment of skeletal defects and diseases. This review will highlight recent advances in the derivation of pluripotent stem cells, and in their directed differentiation towards bone-forming osteoblasts. PMID- 26260199 TI - Cryopreservation of testicular tissue before long-term testicular cell culture does not alter in vitro cell dynamics. AB - OBJECTIVE: To assess whether testicular cell dynamics are altered during long term culture after testicular tissue cryopreservation. DESIGN: Experimental basic science study. SETTING: Reproductive biology laboratory. PATIENT(S): Testicular tissue with normal spermatogenesis was obtained from six donors. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Detection and comparison of testicular cells from fresh and frozen tissues during long-term culture. RESULT(S): Human testicular cells derived from fresh (n = 3) and cryopreserved (n = 3) tissues were cultured for 2 months and analyzed with quantitative reverse-transcription polymerase chain reaction and immunofluorescence. Spermatogonia including spermatogonial stem cells (SSCs) were reliably detected by combining VASA, a germ cell marker, with UCHL1, a marker expressed by spermatogonia. The established markers STAR, ACTA2, and SOX9 were used to analyze the presence of Leydig cells, peritubular myoid cells, and Sertoli cells, respectively. No obvious differences were found between the cultures initiated from fresh or cryopreserved tissues. Single or small groups of SSCs (VASA(+)/UCHL1(+)) were detected in considerable amounts up to 1 month of culture, but infrequently after 2 months. SSCs were found attached to the feeder monolayer, which expressed markers for Sertoli cells, Leydig cells, and peritubular myoid cells. In addition, VASA(-)/UCHL1(+) cells, most likely originating from the interstitium, also contributed to this monolayer. Apart from Sertoli cells, all somatic cell types could be detected throughout the culture period. CONCLUSION(S): Testicular tissue can be cryopreserved before long-term culture without modifying its outcome, which encourages implementation of testicular tissue banking for fertility preservation. However, because of the limited numbers of SSCs available after 2 months, further exploration and optimization of the culture system is needed. PMID- 26260200 TI - Laparoscopic anatomy of the autonomic nerves of the pelvis and the concept of nerve-sparing surgery by direct visualization of autonomic nerve bundles. AB - OBJECTIVE: To demonstrate the laparoscopic neuroanatomy of the autonomic nerves of the pelvis using the laparoscopic neuronavigation technique, as well as the technique for a nerve-sparing radical endometriosis surgery. DESIGN: Step-by-step explanation of the technique using videos and pictures (educational video) to demonstrate the anatomy of the intrapelvic bundles of the autonomic nerve system innervating the bladder, rectum, and pelvic floor. SETTING: Tertiary referral center. PATIENT(S): One 37-year-old woman with an infiltrative endometriotic nodule on the anterior third of the left uterosacral ligament and one 34-year-old woman with rectovaginal endometriosis. INTERVENTION(S): Exposure and preservation by direct visualization of the hypogastric nerve and the inferior hypogastric plexus. MAIN OUTCOME MEASURE(S): Visual control and identification of the autonomic nerve branches of the posterior pelvis. RESULT(S): Exposure and preservation of the hypogastric nerve and the superficial part of the left hypogastric nerve were achieved on the first patient. Nerve roots S2, S3, and S4 were identified on the second patient, allowing for the exposure and preservation of the pelvic splanchnic nerves and the deep portion inferior hypogastric plexus. DISCUSSION(S): Radical surgery for endometriosis can induce urinary dysfunction in 2.4%-17.5% of patients owing to lesion of the autonomic nerves. The surgeon's knowledge of the anatomy of these nerves is the main factor for preserving postoperative urinary function. The following nerves are the intrapelvic part of the autonomic nervous system: the hypogastric nerves, which derive from the superior hypogastric plexus and carry the sympathetic signals to the internal urethral and anal sphincters as well as to the pelvic visceral proprioception; and the pelvic splanchnic nerves, which arise from S2 to S4 and carry nociceptive and parasympathetic signals to the bladder, rectum, and the sigmoid and left colons. The hypogastric and pelvic splanchnic nerves merge into the pararectal fossae to form the inferior hypogastric plexus. Most of the nerve-sparing techniques involve the dissection and exposure of the pelvic splanchnic nerves and the inferior hypogastric plexus. However, knowledge of the topographic anatomy and awareness of the landmarks for avoiding intraoperative nerve injuries seem to be the most important factors in avoiding postoperative bladder and bowel dysfunction, although this latter nerve-sparing technique seems to be associated with reduced radicality and symptom persistence. CONCLUSION(S): This video demonstrates a technique to expose the sympathetic and parasympathetic nerves of the pelvis to preserve them in radical pelvic surgery, by means of direct visualization, in a similar fashion to the technique used to preserve the ureters. An alternative to this technique is to use landmarks for limiting dissection and avoiding intraoperative nerve injury. Despite being safe and more easily reproducible, this latter technique is associated with a higher rate of symptom persistence. PMID- 26260201 TI - Successful treatment algorithm for evaluation of early pregnancy after in vitro fertilization. AB - OBJECTIVE: To evaluate a prospectively implemented clinical algorithm for early identification of ectopic pregnancy (EP) and heterotopic pregnancy (HP) after assisted reproductive technology (ART). DESIGN: Analysis of prospectively collected data. SETTING: Academic medical center. PATIENT(S): All ART-conceived pregnancies between January 1995 and June 2013. INTERVENTION(S): Early pregnancy monitoring via clinical algorithm with all pregnancies screened using human chorionic gonadotropin (hCG) levels and reported symptoms, with subsequent early ultrasound evaluation if hCG levels were abnormal or if the patient reported pain or vaginal bleeding. MAIN OUTCOME MEASURE(S): Algorithmic efficiency for diagnosis of EP and HP and their subsequent clinical outcomes using a binary forward stepwise logistic regression model built to determine predictors of early pregnancy failure. RESULT(S): Of the 3,904 pregnancies included, the incidence of EP and HP was 0.77% and 0.46%, respectively. The algorithm selected 96.7% and 83.3% of pregnancies diagnosed with EP and HP, respectively, for early ultrasound evaluation, leading to earlier treatment and resolution. Logistic regression revealed that first hCG, second hCG, hCG slope, age, pain, and vaginal bleeding were all independent predictors of early pregnancy failure after ART. CONCLUSION(S): Our clinical algorithm for early pregnancy evaluation after ART is effective for identification and prompt intervention of EP and HP without significant over- or misdiagnosis, and avoids the potential catastrophic morbidity associated with delayed diagnosis. PMID- 26260202 TI - Useful signs for the assessment of vascular rings on cross-sectional imaging. AB - Vascular rings can be challenging to diagnose because they can contain atretic portions not detectable with current imaging modalities. In these cases, where the compressed airway and esophagus are not encircled by patent, opacified vessels, there are useful secondary signs that should be considered and should raise suspicion for the presence of a vascular ring. These signs include a double aortic arch, the four-vessel sign, the distorted subclavian artery sign, a diverticulum of Kommerell, a ductal diverticulum contralateral to the aortic arch, and a descending aorta contralateral to the arch or circumflex aorta. If none of these findings is present, a ring can be excluded with confidence. PMID- 26260203 TI - Prenatal evaluation of atelencephaly. AB - Atelencephaly is a rare lethal congenital brain malformation characterized by underdevelopment of the prosencephalon and is often accompanied by the facial features seen in some cases of holoprosencephaly, such as cyclopia. We report a case of atelencephaly in the fetus with characteristic ultrasound findings. In addition, we report the findings on fetal MRI, which have not been previously described in the literature. PMID- 26260204 TI - [Re-bleeding predictors in patients with aneurysmal subarachnoid haemorrhage and delayed neurosurgical treatment]. AB - OBJECTIVE: To evaluate the re-bleeding predictors in patients with delayed treatment of aneurysmal subarachnoid hemorrhage. PATIENTS AND METHODS: A prospective cohort study enrolled 261 patients with aneurysmal subarachnoid hemorrhage, attending in Hermanos Ameijeiras Hospital from October 2005, and June 2014. RESULTS: An increased re-bleeding risk in the multivariate analysis was associated with grade III (OR 2.01; 95% CI; 1.06-3.84) and grade IV (OR 3.84; 95% CI; 2.06-7.31) on World Federation Neurological Surgeon (WFNS) scale; grade III (OR 2.04; 95% CI; 1.01-4.13) and grade IV (OR 2.12, 95% CI; 1.05-4.28) on the Fischer scale, aneurism location in posterior circulation (OR 2.45, 95% CI; 1.33 4.44), and anterior communicant artery (OR 1.57, 95% CI;1.00-2.46). Hypertension history was present in 60.9% (159 patients) and was also associated with risk of re-bleeding (OR 2.70, 95% CI; 1.00-7.30). Blood pressure, haematocrit, glycemic, aneurysm size, multiple aneurysms, and location in the middle cerebral artery, do not show any relationship. CONCLUSION: Hypertension history, poor grade (III and IV) on WFNS and Fisher scale and aneurysm location were independent risks factors of re-bleeding in patients with delayed aneurysmal treatment. PMID- 26260205 TI - [Incidence and causes of early end in awake surgery for language mapping not directly related to eloquence]. AB - The incidence and causes that may lead to an early end (unfinished cortical/subcortical mapping) of awake surgery for language mapping are little known. A study was conducted on 41 patients with brain glioma located in the language area that had awake surgery under conscious sedation. Surgery was ended early in 6 patients. The causes were: tonic-clonic seizure (1), lack of cooperation due to fatigue/sleep (4), whether or not word articulation was involved, a decreased level of consciousness for ammonia encephalopathy that required endotracheal intubation (1). There are causes that could be expected and in some cases avoided. Tumour size, preoperative aphasia, valproate treatment, and type of anaesthesia used are variables to consider to avoid failure in awake surgery for language mapping. With these results, the following measures are proposed: l) If the tumour is large, perform surgery in two times to avoid fatigue, 2) if patient has a preoperative aphasia, do not use sedation during surgery to ensure that sleepiness does not cause worse word articulation, 3) if the patient is on valproate treatment, it is necessary to rule out the pre operative symptoms that are not due to ammonia encephalopathy. PMID- 26260206 TI - [Neuronavigation in the surgical planning of callosotomy]. AB - OBJECTIVE: To describe the usefulness of 3D computer-assisted preoperative neuronavigation for stereoscopic location of the venous sinuses, arterial branches, and corpus callosum, to extrapolate anatomical landmarks on the surgical field and make decisions before the intervention. METHODS: A prospective analysis was performed on patients with refractory epilepsy who underwent neuronavigation-assisted callosotomy (BRAIN LAB Dual). RESULTS: A total of 10 neuronavigation-assisted callosotomies were performed in the year 2014. The ages of the patients (4 males and 6 females) were between 4 and 13 years (mean 7; SD 3.02). The most common indication for callosotomy in our sample was Lennox Gastoux (5 patients). A right parasagittal craniotomy was performed in 8 patients. An anterior two-thirds callosotomy was performed in 8 patients and anterior three-quarters in 2 patients. The mean accuracy of the neuronavigation procedure was less than 2mm. In no cases were there significant intraoperative surgical complications. CONCLUSION: Callosotomy using frameless guided neuronavigation is an accurate and safe technique in patients with epilepsy refractory to surgical resection. PMID- 26260207 TI - [Comment on the study "Re-bleeding predictors in patients with aneurysmal subarachnoid haemorrhage and delayed neurosurgical treatment", by Rivero Rodriguez et al]. PMID- 26260208 TI - Clinical encounters of Australian general practice registrars with Aboriginal and Torres Strait Islander patients. AB - OBJECTIVE: General practice is central to Aboriginal and Torres Strait Islander health care, and this area is a core element of Australian general practice (GP) training. We aimed to describe the prevalence, nature and associations of GP registrar encounters with Aboriginal and Torres Strait Islander patients. METHODS: A cross-sectional analysis from a cohort study of GP registrars' clinical consultations 2010-2013. Registrars record demographic, clinical and educational details of consecutive patient encounters. Multivariable associations were tested with logistic regression. RESULTS: A total of 592 registrars contributed data from 69,188 consultations. Encounters with Aboriginal and Torres Strait Islander patients comprised 1.0% of consultations. Significant positive associations included younger patient age; new patient to the registrar; lower socioeconomic status of practice location; non-urban practice setting; more problems managed; and follow-up arranged. A greater proportion of Aboriginal and Torres Strait Islander patients' problems were psychological/social and a lesser proportion were cardiovascular. Consultation duration did not differ between the two groups Conclusions: GP registrars encounter Aboriginal and Torres Strait Islander patients less than do established GPs. Our results suggest possible variability in registrar experience of Aboriginal and Torres Strait Islander health. IMPLICATIONS: Our findings will inform training of a culturally and clinically competent workforce in this area. PMID- 26260209 TI - Role of complement receptor 1 (CR1; CD35) on epithelial cells: A model for understanding complement-mediated damage in the kidney. AB - The regulators of complement activation gene cluster encodes a group of proteins that have evolved to control the amplification of complement at the critical step of C3 activation. Complement receptor 1 (CR1) is the most versatile of these inhibitors with both receptor and regulatory functions. While expressed on most peripheral blood cells, the only epithelial site of expression in the kidney is by the podocyte. Its expression by this cell population has aroused considerable speculation as to its biologic function in view of many complement-mediated renal diseases. The goal of this investigation was to assess the role of CR1 on epithelial cells. To this end, we utilized a Chinese hamster ovary cell model system. Among our findings, CR1 reduced C3b deposition by ~ 80% during classical pathway activation; however, it was an even more potent regulator (>95% reduction in C3b deposition) of the alternative pathway. This inhibition was primarily mediated by decay accelerating activity. The deposited C4b and C3b were progressively cleaved with a t1/2 of ~ 30 min to C4d and C3d, respectively, by CR1-dependent cofactor activity. CR1 functioned intrinsically (i.e, worked only on the cell on which it was expressed). Moreover, CR1 efficiently and stably bound but didn't internalize C4b/C3b opsonized immune complexes. Our studies underscore the potential importance of CR1 on an epithelial cell population as both an intrinsic complement regulator and an immune adherence receptor. These results provide a framework for understanding how loss of CR1 expression on podocytes may contribute to complement-mediated damage in the kidney. PMID- 26260211 TI - Glucose, glycolysis and lymphocyte responses. AB - Activated lymphocytes engage in robust growth and rapid proliferation. To achieve this, they tend to adopt a form of glucose metabolism termed aerobic glycolysis. This type of metabolism allows for the use of large amounts of glucose to generate energy, but also to support biosynthetic processes. This review article will discuss how aerobic glycolysis supports the biosynthetic demands of activated T cells, B cells and Natural Killer cells, and the emerging concept that glycolysis is integrally linked to the differentiation and function of these lymphocyte populations. PMID- 26260212 TI - The role of dendritic cell alterations in susceptibility to hospital-acquired infections during critical-illness related immunosuppression. AB - Systemic inflammatory response syndrome (SIRS) is a common condition in critically ill patients. SIRS is characterized by alteration of both innate and adaptive immunity and causes protracted immunosupression, exposing the patients to severe secondary infections. Dendritic cells (DCs), which play a pivotal role bridging innate and T cell-dependent immunity, exhibit prolonged alterations after SIRS. In an early phase, SIRS causes depletion or systemic activation of immature DCs in parenchymal tissues and lymphoid organs, leading to impaired pathogen detection and presentation. Later on, newly formed DCs acquire a poorly immunogenic phenotype, with poor capacity to capture, process and/or present antigens and to stimulate T cells. Here, we review the studies that describe alterations in DC function post-SIRS. Knowledge about the molecular mechanisms involved are still scarce but their understanding might open new therapeutic avenues to prevent or reduce protracted immunosuppression in critically-ill patients. PMID- 26260213 TI - Assessing pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a systematic review. AB - AIM: Pathological complete response to neoadjuvant chemoradiotherapy is found in 20% of patients with rectal cancer undergoing long-course chemoradiotherapy. Some authors have suggested that these patients do not need to undergo surgery and can be managed with careful follow-up, with surgery only used in the event of clinical failure. Widespread adoption of this regimen is limited by the accuracy of methods to confirm a pathological complete response (pCR). METHOD: A systematic search of PubMed, Medline and Cochrane databases was conducted to identify clinical, histological and radiological features in those patients with rectal cancer who achieved a pCR following chemoradiotherapy. Searches were conducted with the following keywords and MeSH search terms: 'rectal neoplasm', 'response', 'neoadjuvant', 'preoperative chemoradiation' and 'tumour response'. After review of title and abstracts, 89 articles addressing the assessment of pCR were identified. RESULTS: Histology and clinical assessment are the most effective methods of assessment of pCR, with histology considered the gold standard. Clinical assessment is limited to low rectal tumours and is open to significant inter-rater variability, while histological examination requires a surgical specimen. Diffusion-weighted MRI and (18) F-fluorodeoxyglucose positron emission tomography/CT demonstrate the greatest potential for the assessment of pCR, but both modalities have limited accuracy. CONCLUSION: Determination of a pCR is crucial if a nonoperative approach is to be undertaken proactively. Various methods are available, but currently they lack sufficient sensitivity and specificity to define management. This is likely to be an area of further research in the future. PMID- 26260210 TI - TCR signaling to NF-kappaB and mTORC1: Expanding roles of the CARMA1 complex. AB - Naive T-cell activation requires signals from both the T-cell receptor (TCR) and the costimulatory molecule CD28. A central mediator of the TCR and CD28 signals is the scaffold protein CARMA1, which functions by forming a complex with partner proteins, Bcl10 and MALT1. A well-known function of the CARMA1 signaling complex is to mediate activation of IkappaB kinase (IKK) and its target transcription factor NF-kappaB, thereby promoting T-cell activation and survival. Recent evidence suggests that CARMA1 also mediates TCR/CD28-stimulated activation of the IKK-related kinase TBK1, which plays a role in regulating the homeostasis and migration of T cells. Moreover, the CARMA1 complex connects the TCR/CD28 signals to the activation of mTORC1, a metabolic kinase regulating various aspects of T cell functions. This review will discuss the mechanism underlying the activation of the CARMA1-dependent signaling pathways and their roles in regulating T-cell functions. PMID- 26260214 TI - Variation in PARK10 is not associated with risk and age at onset of Parkinson's disease in large clinical cohorts. AB - A recent study in autopsy-confirmed Parkinson's disease (PD) patients and controls revived the debate about the role of PARK10 in this disorder. In an attempt to replicate these results and further understand the role of this locus in the risk and age at onset of PD, we decided to explore NeuroX genotyping and whole exome sequencing data from 2 large independent cohorts of clinical patients and controls from the International Parkinson's Disease Genomic Consortium. A series of single-variant and gene-based aggregation (sequence kernel association test and combined multivariate and collapsing test) statistical tests suggested that common and rare genetic variation in this locus do not influence the risk or age at onset of clinical PD. PMID- 26260215 TI - Adoptive Transfer of Renal Allograft Tolerance in a Large Animal Model. AB - Our recent studies in an inbred swine model demonstrated that both peripheral and intra-graft regulatory cells were required for the adoptive transfer of tolerance to a second, naive donor-matched kidney. Here, we have asked whether both peripheral and intra-graft regulatory elements are required for adoptive transfer of tolerance when only a long-term tolerant (LTT) kidney is transplanted. Nine highly-inbred swine underwent a tolerance-inducing regimen to prepare LTT kidney grafts which were then transplanted to histocompatible recipients, with or without the peripheral cell populations required for adoptive transfer of tolerance to a naive kidney. In contrast to our previous studies, tolerance of the LTT kidney transplants alone was achieved without transfer of additional peripheral cells and without strategies to increase the number/potency of regulatory T cells in the donor. This tolerance was systemic, since most subsequent, donor-matched challenge kidney grafts were accepted. These results confirm the presence of a potent tolerance-inducing and/or tolerance-maintaining cell population within LTT renal allografts. They suggest further that additional peripheral tolerance mechanisms, required for adoptive transfer of tolerance to a naive donor-matched kidney, depend on peripheral cells that, if not transferred with the LTT kidney, require time to develop in the adoptive host. PMID- 26260216 TI - Effects of a Specialist-Led, School Physical Education Program on Bone Mass, Structure, and Strength in Primary School Children: A 4-Year Cluster Randomized Controlled Trial. AB - This 4-year cluster randomized controlled trial of 365 boys and 362 girls (mean age 8.1 +/- 0.3 years) from grade 2 in 29 primary schools investigated the effects of a specialist-taught physical education (PE) program on bone strength and body composition. All children received 150 min/week of common practice (CP) PE from general classroom teachers but in 13 schools 100 min/week of CP PE was replaced by specialized-led PE (SPE) by teachers who emphasized more vigorous exercise/games combined with static and dynamic postural activities involving muscle strength. Outcome measures assessed in grades 2, 4, and 6 included: total body bone mineral content (BMC), lean mass (LM), and fat mass (FM) by DXA, and radius and tibia (4% and 66% sites) bone structure, volumetric density and strength, and muscle cross-sectional area (CSA) by pQCT. After 4-years, gains in total body BMC, FM, and muscle CSA were similar between the groups in both sexes, but girls in the SPE group experienced a greater gain in total body LM (mean 1.0 kg; 95% CI, 0.2 to 1.9 kg). Compared to CP, girls in the SPE group also had greater gains in cortical area (CoA) and cortical thickness (CoTh) at the mid tibia (CoA, 5.0% [95% CI, 0.2% to 1.9%]; CoTh, 7.5% [95% CI, 2.4% to 12.6%]) and mid-radius (CoA, 9.3% [95% CI, 3.5% to 15.1%]; CoTh, 14.4% [95% CI, 6.1% to 22.7%]), whereas SPE boys had a 5.2% (95% CI, 0.4% to 10.0%) greater gain in mid tibia CoTh. These benefits were due to reduced endocortical expansion. There were no significant benefits of SPE on total bone area, cortical density or bone strength at the mid-shaft sites, nor any appreciable effects at the distal skeletal sites. This study indicates that a specialist-led school-based PE program improves cortical bone structure, due to reduced endocortical expansion. This finding challenges the notion that periosteal apposition is the predominant response of bone to loading during the prepubertal and early-pubertal period. PMID- 26260217 TI - Antonello da Messina: Virgin Annunciate. PMID- 26260218 TI - A novel SLC12A3 gene homozygous mutation of Gitelman syndrome in an Asian pedigree and literature review. AB - OBJECTIVES: Gitelman syndrome (GS) is an autosomal recessive disease characterized by hypokalemic metabolic alkalosis in combination with significant hypomagnesemia and hypocalciuria which is caused by mutations in the SLC12A3 gene. In this study, we reported a case of GS pedigree and reviewed pertinent literature so as to explore the relationship between clinical characteristics and genotype meanwhile provide recommendations for the diagnosis and treatment of GS. DESIGN AND METHODS: This is a pedigree-based genetic study of GS and 11 members from one family were included. We summarized their clinical features, analyzed laboratory parameters related to GS and SLC12A3 gene. RESULTS: The proband experienced intermittent severe symptoms of weakness accompanied by significant hypokalemia, hypomagnesemia and hypocalciuria in laboratory test with poor treatments. His mother had more slight symptoms of weakness than him with mild hypokalemia and hypocalciuria. Mild hypomagnesemia was also observed in his sister with occasional weakness. All other pedigree members had normal laboratory test with no GS-related symptoms. A homozygous mutation of SLC12A3 gene (c.488C > T) was detected by genetic testing in three members, and six were carriers of this mutation. CONCLUSIONS: Genotype and phenotype vary significantly among GS patients. Male patients tend to experience more severe symptoms and poor treatment effect. Further large-scale population, animal, and molecular biology experiments are required to investigate the complexity of GS and to find a better treatment regimen for this disease. PMID- 26260219 TI - Clinicopathological significance of N-cadherin and VEGF in advanced gastric cancer brain metastasis and the effects of metformin in preclinical models. AB - Gastric cancer is the second most common cause of cancer-related death worldwide. Although brain metastasis is a rare complication of gastric cancer, no standard therapy for gastric cancer brain metastasis has been established. We attempted to identify biological markers that predict brain metastasis, and investigated how to modulate such markers. A case-control study of patients newly diagnosed with gastric cancer who had developed brain metastasis during follow-up, was conducted. These patients were compared with patients who had advanced gastric cancer but no evidence of brain metastasis. Immunohistochemistry was used to analyze the expression of E-cadherin, N-cadherin, MSS1, claudin-3, claudin-4, Glut1, clusterin, ITGB4, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) and p53. The expression of VEGF tended to be higher in the case group (33.3 vs. 0%, p=0.055). Median survival was significantly correlated with vascular invasion (12 vs. 33 months, p=0.008) and N-cadherin expression (36 vs. 12 months, p=0.027). We also investigated the effects of metformin in tumor-bearing mouse models. VEGF expression was decreased and E cadherin increased in the metformin-treated group when compared with the control group. The expression of the mesenchymal marker MMP9 was decreased in the metformin-treated group. Brain metastasis of advanced gastric cancer was associated with the expression of VEGF. Metformin treatment may be useful for modulating the metastatic capacity by reducing VEGF expression and blocking epithelial-to-mesenchymal transition. PMID- 26260221 TI - Reply to the Editor--A novel method to predict the proportional risk from sudden cardiac death in heart failure: Derivation of the Seattle Proportional Risk Model. PMID- 26260220 TI - Uric Acid: A Missing Link Between Hypertensive Pregnancy Disorders and Future Cardiovascular Disease? AB - OBJECTIVE: To determine whether women who had a hypertensive pregnancy disorder (HPD) have elevated uric acid concentrations decades after pregnancy as compared with women who had normotensive pregnancies. PATIENTS AND METHODS: The Genetic Epidemiology Network of Arteriopathy study measured uric acid concentrations in Hispanic (30%), non-Hispanic white (28%), and non-Hispanic black (42%) women (mean age, 60 +/- 10 years). This cross-sectional study was conducted between July 1, 2000, and December 31, 2004. Hispanic participants were recruited from families with high rates of diabetes, whereas non-Hispanic participants were recruited from families with high rates of hypertension. This analysis compared uric acid concentrations in women with a history of normotensive (n = 1846) or hypertensive (n = 408) pregnancies by logistic regression. RESULTS: Women who had an HPD had higher uric acid concentrations (median, 5.7 mg/dL vs 5.3 mg/dL; P < .001) and were more likely to have uric acid concentrations above 5.5 mg/dL (54.4% vs 42.4%; P = .001) than were women who had normotensive pregnancies. These differences persisted after adjusting for traditional cardiovascular risk factors, comorbidities, and other factors that affect uric acid concentrations. A family-based subgroup analysis comparing uric acid concentrations in women who had an HPD (n = 308) and their parous sisters who had normotensive pregnancies (n = 250) gave similar results (median uric acid concentrations, 5.7 mg/dL vs 5.2 mg/dL, P = 0.02; proportion of women with uric acid concentrations > 5.5 mg/dL, 54.0% vs 40.3%, P < .001). CONCLUSION: Decades after pregnancy, women who had an HPD have higher uric acid concentrations. This effect does not appear to be explained by a familial predisposition to elevated uric acid concentrations. PMID- 26260222 TI - Pyrazolopyrimidines: Potent Inhibitors Targeting the Capsid of Rhino- and Enteroviruses. AB - There are currently no drugs available for the treatment of enterovirus (EV) induced acute and chronic diseases such as the common cold, meningitis, encephalitis, pneumonia, and myocarditis with or without consecutive dilated cardiomyopathy. Here, we report the discovery and characterization of pyrazolopyrimidines, a well-tolerated and potent class of novel EV inhibitors. The compounds inhibit the replication of a broad spectrum of EV in vitro with IC50 values between 0.04 and 0.64 MUM for viruses resistant to pleconaril, a known capsid-binding inhibitor, without affecting cytochrome P450 enzyme activity. Using virological and genetics methods, the viral capsid was identified as the target of the most promising, orally bioavailable compound 3-(4 trifluoromethylphenyl)amino-6-phenylpyrazolo[3,4-d]pyrimidine-4-amine (OBR-5 340). Its prophylactic as well as therapeutic application was proved for coxsackievirus B3-induced chronic myocarditis in mice. The favorable pharmacokinetic, toxicological, and pharmacodynamics profile in mice renders OBR 5-340 a highly promising drug candidate, and the regulatory nonclinical program is ongoing. PMID- 26260223 TI - Circular Dichroism of Amino Acids: Following the Structural Formation of Phenylalanine. AB - Circular dichroism (CD) is frequently used to assess the secondary structure of peptides and proteins, whereas less attention has been given to their building blocks, that is, single amino acids, as they do not possess a secondary structure. Here, we follow the CD signal of amino acids and reveal that several acids exhibit a unique CD pattern as a function of their concentration. Accordingly, we propose an eight-level classification of the CD signal of the various amino acids. Special focus is given to the CD pattern of phenylalanine (Phe), for which we observe the formation of an ultra-narrow CD peak (full width at high maximum of only 5 nm). This CD peak can be attributed to the formation of Phe-based chiral structural features. Further support for the formation of an ordered structure is given by using NMR, and the additional self-assembly process of Phe to tubular structures. PMID- 26260224 TI - Outcome prediction by extranodal involvement, IPI, R-IPI, and NCCN-IPI in the PET/CT and rituximab era: A Danish-Canadian study of 443 patients with diffuse large B-cell lymphoma. AB - 18F-fluorodeoxyglucose PET/CT (PET/CT) is the current state-of-the-art in the staging of diffuse large B-cell lymphoma (DLBCL) and has a high sensitivity for extranodal involvement. Therefore, reassessment of extranodal involvement and the current prognostic indices in the PET/CT era is warranted. We screened patients with newly diagnosed DLBCL seen at the academic centers of Aalborg, Copenhagen, and British Columbia for eligibility. Patients that had been staged with PET/CT and treated with R-CHOP(-like) 1(st) line treatment were retrospectively included. In total 443 patients met the inclusion criteria. With a median follow up of 2.4 years, the 3-year overall (OS) and progression-free survival (PFS) were 73% and 69%, respectively. The Ann Arbor classification had no prognostic impact in itself with the exception of stage IV disease (HR 2.14 for PFS, P<0.01). Extranodal involvement was associated with a worse outcome in general, and in particular for patients with involvement of >2 extranodal sites, including HR 7.81 (P < 0.001) for PFS for >3 sites. Bone/bone marrow involvement was the most commonly involved extranodal site identified by PET/CT (29%) and was associated with an inferior PFS and OS. The IPI, R-IPI, and NCCN-IPI were predictive of PFS and OS, and the two latter could identify a very good prognostic subgroup with 3 year PFS and OS of 100%. PET/CT-ascertained extranodal involvement in DLBCL is common and involvement of >2 extranodal sites is associated with a dismal outcome. The IPI, R-IPI, and NCCN-IPI predict outcome with high accuracy. PMID- 26260225 TI - Statins and new-onset diabetes mellitus - a risk lacking in familial hypercholesterolaemia. PMID- 26260227 TI - Editorial overview: Oncolytic viruses--replicating virus therapeutics for the treatment of cancer. PMID- 26260226 TI - 2D and 3D crystallization of the wild-type IIC domain of the glucose PTS transporter from Escherichia coli. AB - The bacterial phosphoenolpyruvate: sugar phosphotransferase system serves the combined uptake and phosphorylation of carbohydrates. This structurally and functionally complex system is composed of several conserved functional units that, through a cascade of phosphorylated intermediates, catalyze the transfer of the phosphate moiety from phosphoenolpyruvate to the substrate, which is bound to the integral membrane domain IIC. The wild-type glucose-specific IIC domain (wt IIC(glc)) of Escherichia coli was cloned, overexpressed and purified for biochemical and functional characterization. Size-exclusion chromatography and scintillation-proximity binding assays showed that purified wt-IIC(glc) was homogenous and able to bind glucose. Crystallization was pursued following two different approaches: (i) reconstitution of wt-IIC(glc) into a lipid bilayer by detergent removal through dialysis, which yielded tubular 2D crystals, and (ii) vapor-diffusion crystallization of detergent-solubilized wt-IIC(glc), which yielded rhombohedral 3D crystals. Analysis of the 2D crystals by cryo-electron microscopy and the 3D crystals by X-ray diffraction indicated resolutions of better than 6A and 4A, respectively. Furthermore, a complete X-ray diffraction data set could be collected and processed to 3.93A resolution. These 2D and 3D crystals of wt-IIC(glc) lay the foundation for the determination of the first structure of a bacterial glucose-specific IIC domain. PMID- 26260228 TI - "Micro to macro (M2M)"--A novel approach for intravenous delivery of propofol. AB - PURPOSE: Propofol emulsions have limited shelf life and safety concerns for injection. Microemulsions of propofol are thermodynamically stable and simpler to manufacture, but cause additional pain on injection. We propose a novel micro to macro (M2M) approach of destabilizing a microemulsion immediately prior to injection. METHODS: Microemulsions of propofol were prepared at two to three times the drug loadings of commercial formulations. We determined suitable microemulsion compositions which destabilize into macroemulsions after two or three fold dilutions with water. Droplet growth after dilution was measured with dynamic light scattering. Increasing solution turbidity after dilution was also measured optically with millisecond resolution. Experimental data was analyzed in the context of a coalescence model. RESULTS: Microemulsions rapidly coalesce into larger droplet size macroemulsions after dilution according to the phase diagram shift. The resulting macroemulsions are metastable retaining their droplet size for several hours. Droplet growth occurs on the order of seconds and a metastable size of about 1 micron is reached in minutes. Rates of droplet growth and metastable droplet sizes depend on the surfactant composition. The coalescence model predicts droplet growth with good agreement but only after accounting for the finite probability of coalescence from each collision. CONCLUSIONS: The M2M concept has been demonstrated for the anesthetic drug propofol which may improve stability and manufacturability in addition to reducing pain on injection. This approach could be adapted to other hydrophobic vesicant drugs as well. PMID- 26260229 TI - Markedly lowering the viscosity of aqueous solutions of DNA by additives. AB - Aqueous solutions of DNAs, while relevant in drug delivery and as a target of therapies, are often very viscous making them difficult to use. Since less viscous solutions could enable targeted drug delivery and/or therapies, the purpose of the present work was to explore compounds capable of "thinning" such DNA solutions under pharmaceutically relevant conditions. To this end, viscosities of aqueous solutions of DNAs and model polyanions were examined at 25 degrees C in the absence and presence of a number of bulky organic salts (and related compounds) previously found to substantially lower the viscosities of concentrated protein solutions. Out of two dozen compounds tested, only three were found to be effective; the FDA-approved local anesthetics lidocaine, mepivacaine, and prilocaine at near-isotonic concentrations and pH 6.4 lowered solution viscosity of three different DNAs up to about 20 fold. The observed multi-fold viscosity reductions appear to be due to these bulky organic salts' structure-specific non-covalent binding to nucleotide bases resulting in denaturation (unwinding) to, and stabilization of, single-stranded DNA. PMID- 26260230 TI - Recent advances in local drug delivery to the inner ear. AB - Inner ear diseases are not adequately treated by systemic drug administration mainly because of the blood-perilymph barrier that reduces exchanges between plasma and inner ear fluids. Local drug delivery methods including intratympanic and intracochlear administrations are currently developed to treat inner ear disorders more efficiently. Intratympanic administration is minimally invasive but relies on diffusion through middle ear barriers for drug entry into the cochlea, whereas intracochlear administration offers direct access to the colchlea but is rather invasive. A wide range of drug delivery systems or devices were evaluated in research and clinic over the last decade for inner ear applications. In this review, different strategies including medical devices, hydrogels and nanoparticulate systems for intratympanic administration, and cochlear implant coating or advanced medical devices for intracoclear administration were explored with special attention to in vivo studies. This review highlights the promising systems for future clinical applications as well as the current hurdles that remain to be overcome for efficient inner ear therapy. PMID- 26260231 TI - An optimized gastroretentive nanosystem for the delivery of levodopa. AB - Characterization of the physicochemical and physicomechanical properties as well as biopharmaceutical suitability of a drug delivery system is needful in optimization of the formulation and manufacturing processes in order to achieve the desired responses. Interpolymeric blend (IPB) nano-enabled gastroretentive levodopa-loaded drug delivery systems were formulated, optimized and characterized using techniques such as spectroscopy, calorimetry, density, textural analysis, morphological analysis, porosity analysis and magnetic resonance imaging. The in vitro drug release of the delivery systems was compared to those of the conventional dosage forms and in vivo absorption was predicted. The average densities were 1.41 mg/mm(3) and 1.56 mg/mm(3) for the two formulations; rigidities were 75.05 N/mm and 84.93 N/mm; and 92% of the pores of the IPB drug delivery system were mesoporous. MR imaging displayed the swollen front at pH 1.5 and the eroded front at pH 4.5. In comparisons to the conventional dosage forms, the IPB nano-enabled gastroretentive levodopa-loaded drug delivery systems exhibited drug release over a prolonged period of time and levodopa-loaded IPB matrices were the best fit for zero-order release. Indeed the analyses of IPB nano-enabled gastroretentive levodopa-loaded drug delivery systems indicate that they hold promise as sustained delivery system for management of Parkinson's disease. PMID- 26260232 TI - Calcium-permeable AMPA receptors trigger vesicular glutamate release from Bergmann gliosomes. AB - The Bergmann glia is equipped with Ca2+-permeable AMPA receptors for glutamate, indispensable for structural and functional relations between the Bergmann glia and parallel/climbing fibers-Purkinje cell synapses. To better understand roles for the Bergmann AMPA receptors, herein we investigate on gliotransmitter release and Ca2+ signals in isolated Bergmann glia processes obtained from adult rat cerebellum. We found that: 1) the rat cerebellar purified astrocyte processes (gliosomes) expressed astrocytic and Bergmann markers and exhibited negligible contamination by nerve terminals, microglia, or oligodendrocytes; 2) activation of Ca2+-permeable AMPA receptors caused Ca2+ signals in the processes, and the release of glutamate from the processes; 3) effectiveness of rose bengal, trypan blue or bafilomycin A1, indicated that activation of the AMPA receptors evoked vesicular glutamate release. Cerebellar purified nerve terminals appeared devoid of glutamate-releasing Ca2+-permeable AMPA receptors, indicating that neuronal contamination may not be the source of the signals detected. Ultrastructural analysis indicated the presence of vesicles in the cytoplasm of the processes; confocal imaging confirmed the presence of vesicular glutamate transporters in Bergmann glia processes. We conclude that: a vesicular mechanism for release of the gliotransmitter glutamate is present in mature Bergmann processes; entry of Ca2+ through the AMPA receptors located on Bergmann processes is coupled with vesicular glutamate release. The findings would add a new role for a well-known Bergmann target for glutamate (the Ca2+-permeable AMPA receptors) and a new actor (the gliotransmitter glutamate) at the cerebellar excitatory synapses onto Purkinje cells. PMID- 26260233 TI - Diagnosis of dementia by medical practitioners: a national study among older adults in Singapore. AB - OBJECTIVES: Dementia is inevitably associated with an ageing population which has tremendous public health, social and economic implications. Yet the extant evidence suggests that the diagnosis of dementia in general is neither timely nor accurate. The aim of this present study was to establish the prevalence of dementia as diagnosed by medical practitioners in Singapore and its associated factors. METHOD: The analysis is based on a national epidemiological study of older adults in Singapore which had established the prevalence of dementia using the 10/66 protocol. It was a community based survey, and face-to-face interviews were conducted with 2565 respondents (a response rate of 66%) and 2421 informants. RESULTS: In all, 3% of the respondents were diagnosed by a medical practitioner to have dementia of which 11.5% were diagnosed by general practitioners. Only 30.3% were prescribed medications specifically for dementia. Those with comorbid depression were more likely to be diagnosed to have dementia. CONCLUSION: The apparent low rate of diagnosis by medical practitioners is in line with studies done in the West. There is a need to elucidate the reasons underlying this under-diagnosis in order to better address this gap. PMID- 26260234 TI - Analysis of TTSuV1b antibody in porcine serum and its correlation with four antibodies against common viral infectious diseases. AB - BACKGROUND: The purpose of the present study was to evaluate the correlation between Torque teno sus virus 1b (TTSuV1b) infection and other viral infections or vaccine immunization in conventional pigs. METHODS: With overexpressed and purified viral protein TTSuV1b as antigen, an indirect enzyme-linked immunosorbent assay (ELISA) method for detecting TTSuV1b antibody was established, which demonstrated great specificity and reproducibility. Porcine serum samples (n = 212) were tested using ELISA. Meanwhile, the antibodies against Classical Swine Fever Virus (CSFV), Pseudorabies Virus (PRV), Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), and Porcine Circovirus 2 (PCV2) were also examined using the commercial kits. RESULTS: Statistical analysis indicated that the level of anti-TTSuV1b antibody was positively correlated with the level of anti-PCV2 antibody in a lesser extent; the level of antibodies against TTSuV1b or PCV2 were significantly lower in porcine serum with low level of TTSuV1b virus, implicating the potential consistency and synchronization in the mechanism of TTSuV1b and PCV2 infection. Whereas, antibodies against PRRSV or CSFV showed no statistical significance on comparison with anti-TTSuV1b antibody, implicating that in conventional pigs, the antibody level for PRRSV and CSFV were not significantly influenced by TTSuV1b infection. CONCLUSION: In conclusion, examination of anti-TTSuV1b antibody in porcine serum with the presently established ELISA method would serve as a supplementary approach for etiological investigation, and the combined statistical analysis of the antibodies against four other viruses might help to further understand the TTSuV1b infection as well as its pathogenicity. PMID- 26260235 TI - Integrative Leadership: An Embodied Practice. PMID- 26260236 TI - Dancing Mindfulness: A Phenomenological Investigation of the Emerging Practice. AB - An extensive review of both quantitative and qualitative literature reveals numerous connections between mindfulness practice and psychological well-being. Dancing Mindfulness, as a holistic wellness practice, is a creative approach to mindfulness meditation that draws on dance as the vehicle for engaging in the ancient practice characterized by non-judgment, loving kindness, and present centered awareness. Of the first participants who learned the Dancing Mindfulness practice in a community-based setting, 10 shared their lived experience with the practice, and these experiences were analyzed using A.P. Giorgi's descriptive phenomenological psychological method. As a collective sample, the women described positive experiences with the Dancing Mindfulness practice. Specific themes indicated improvements in emotional and spiritual well-being, increased acceptance, positive changes to the self, and increased application of mindfulness techniques and strategies to real-world living. Another thematic area suggested that dancing and music are the two major components of action within Dancing Mindfulness leading to these benefits. PMID- 26260238 TI - Binding interaction of SGLT with sugar and thiosugar by the molecular dynamics simulation. AB - The human sodium-glucose co-transporter 2 (hSGLT2) is a transporter responsible for reabsorption of glucose in the proximal convoluted tubule of the kidney. hSGLT2 inhibitors, including luseogliflozin, have been developed as drugs for type 2 diabetes mellitus. Only luseogliflozin contains a thiosugar ring in its chemical structure, while other hSGLT2 inhibitors contain glucose rings. Consequently, we focused on the binding interactions of hSGLT2 with sugars and thiosugars. We first revealed that the binding affinities of thiosugars are stronger than those of sugars through molecular dynamics simulations of Vibrio parahaemolyticus, sodium-galactose co-transporter, and human hSGLT2. We then demonstrated that Na(+) dissociates from the protein to the cytoplasmic solution more slowly in the thiosugar system than in the sugar system. These differences between sugars and thiosugars are discussed on the basis of the different binding modes due to the atom at the 5-position of the sugar and thiosugar rings. Finally, as a result of Na(+) dissociation, we suggest that the dissociation of thiosugars is slower than that of sugars. PMID- 26260237 TI - A fresh look at zebrafish from the perspective of cancer research. AB - Zebrafish represent a vertebrate model organism that has been widely, and increasingly, employed over the last decade in the study of developmental processes, wound healing, microbe-host interactions, and drug screening. With the increase in the laboratory use of zebrafish, several advantages, such as a high genetic homology to humans and transparent embryos, which allow clear disease evaluation, have greatly widened its use as a model for studying tumor development in vivo. The use of zebrafish has been applied in several areas of cancer research, mainly in the following domains: (1) establishing cancer models by carcinogenic chemical, genetic technology, and xenotransplantation; (2) evaluating tumor angiogenesis; (3) studying tumor metastasis; and (4) anti-tumor drug screening and drug toxicity evaluation. In this study, we provide a comprehensive overview of the role of zebrafish in order to underline the advantages of using them as a model organism in cancer research. Several related successful events are also reviewed. PMID- 26260239 TI - Monocyte nadir is a possible indicator for neutrophil nadir during lung cancer chemotherapy. AB - INTRODUCTION: No previous study clearly demonstrated the association between the absolute neutrophil count (ANC) nadir and the absolute monocyte count (AMC) nadir among patients undergoing chemotherapy. METHODS: We retrospectively reviewed patients with an incurable lung cancer in two university hospital who were treated with platinum doublet or triplet. In this study, the nadir was defined as the lowest value during days 1-22. RESULTS: We observed 75 patients: 61 men (81%) and 14 women (19%), median age of 69 years. The number of days that elapsed between the first day of chemotherapy and the median ANC nadir of 12 days was longer than that for AMC nadir of 6 (Wilcoxon signed rank test: P < 0.001). The number of days that elapsed between the first day of chemotherapy and the AMC nadir was the only factor that had a significant correlation with that for ANC nadir (Spearman's rank correlation: r = 0.34, P = 0.003). Among 75 patients, 23 (31%) had an ANC at nadir <1000/MUL. AMC at nadir of 100/MUL predicted an ANC at nadir <1000/MUL with a sensitivity of 83% and a specificity of 56%. CONCLUSION: Both neutrophils and monocytes are differentiated from a common progenitor, a granulocyte macrophage colony forming cell, which can provide good explanation for the association between ANC and AMC nadirs. We would like to recommend physicians to observe the AMC nadir to predict the timing and severity of the ANC nadir. PMID- 26260240 TI - The Effects of Combined Treatment with Naringin and Treadmill Exercise on Osteoporosis in Ovariectomized Rats. AB - Osteoporosis is a disease characterized by low bone mass and progressive destruction of bone microstructure, resulting in increased the risk of fracture. Previous studies have demonstrated the effect of naringin (NG) or treadmill exercise (EX) on osteoporosis, however, reports about effects of NG plus EX on osteoporosis are limited. This study was designed to investigate the impact of combined treatment with naringin and treadmill exercise on osteoporosis in ovariectomized (OVX) rats. Three months after bilateral ovariectomy, Seventy-five rats were randomly assigned to the following treatment groups: OVX, sham-operated (SHAM), NG, EX, or NG plus EX treatment. Treatments were administered for 60 days. Bone metabolism, bone mineral density, trabecular bone parameters, immunohistochemistry, and the bone strength were evaluated. Compared to the OVX groups, all treatments increased bone volume (BV/TV), trabecula number (Tb.N), trabecula thickness (Tb.Th), bone mineral density (BMD), and mechanical strength. NG + EX showed the strongest effects on BV/TV, Tb.Th, and biomechanical strength. Additionally, decreased C-terminal telopeptides of type I collagen (CTX-1) and enhanced osteocalcin (OCN) expression were observed in the NG + EX group. The present study demonstrates that the NG + EX may have a therapeutic advantage over each monotherapy for the treatment of osteoporosis. PMID- 26260241 TI - Proteome Analysis Unravels Mechanism Underling the Embryogenesis of the Honeybee Drone and Its Divergence with the Worker (Apis mellifera lingustica). AB - The worker and drone bees each contain a separate diploid and haploid genetic makeup, respectively. Mechanisms regulating the embryogenesis of the drone and its mechanistic difference with the worker are still poorly understood. The proteomes of the two embryos at three time-points throughout development were analyzed by applying mass spectrometry-based proteomics. We identified 2788 and 2840 proteins in the worker and drone embryos, respectively. The age-dependent proteome driving the drone embryogenesis generally follows the worker's. The two embryos however evolve a distinct proteome setting to prime their respective embryogenesis. The strongly expressed proteins and pathways related to transcriptional-translational machinery and morphogenesis at 24 h drone embryo relative to the worker, illustrating the earlier occurrence of morphogenesis in the drone than worker. These morphogenesis differences remain through to the middle-late stage in the two embryos. The two embryos employ distinct antioxidant mechanisms coinciding with the temporal-difference organogenesis. The drone embryo's strongly expressed cytoskeletal proteins signify key roles to match its large body size. The RNAi induced knockdown of the ribosomal protein offers evidence for the functional investigation of gene regulating of honeybee embryogenesis. The data significantly expand novel regulatory mechanisms governing the embryogenesis, which is potentially important for honeybee and other insects. PMID- 26260242 TI - Technique of anatomical single bundle ACL reconstruction with rounded rectangle femoral dilator. AB - BACKGROUND: This study aimed to present a new technique for anatomical single bundle anterior cruciate ligament (ACL) reconstruction. We developed an original rounded rectangular dilator set to create rounded rectangular femoral tunnels. This technique can increase the femoral tunnel size without roof impingement, and has the potential to reduce the graft failure rate. We investigated the tunnel position and the incidence of intraoperative complications. METHOD: The presented technique is anatomical single bundle ACL reconstruction using a semitendinosus graft (with or without the gracilis tendon). The tunnel was drilled via an additional medial portal. Rounded rectangular tunnels were created using a special dilator. Tibial tunnels were created using conventional rounded tunnels. Fixation was achieved using a suspensory device on the femoral side and a plate and screw on the tibial side. PATIENTS: Fifty patients underwent this surgery, and intraoperative complications were investigated. The femoral tunnel positions were documented postoperatively from computed tomography scans using the quadrant method. The tibial tunnel positions (anterior-to-posterior, medial-to-lateral) were documented using intraoperative X-ray scans. RESULTS: Only one patient had a partial posterior tunnel wall blowout. The femoral tunnel length varied between 30 and 40mm (mean, 34.9+/-3.3mm). All femoral and tibial tunnels were located within the area of the anatomical ACL insertions. CONCLUSION: We did not experience any serious intraoperative complications during anatomical single bundle ACL reconstruction using a rounded rectangle dilator, and the resulting locations of the femoral and tibial tunnels were within the anatomical ACL footprint. LEVEL OF EVIDENCE: Level IV. PMID- 26260243 TI - Factors associated with a more rapid recovery after anterior cruciate ligament reconstruction using multivariate analysis. AB - BACKGROUND: In the past, several studies investigated factors that are prognostic or associated with outcome after anterior cruciate ligament (ACL) reconstruction. A recent review showed that only limited evidence is available for most studied factors, and that insufficient analysis methods were used commonly. Therefore, the aim of this study was to add more weight to the existing evidence, about factors that are associated with a more rapid outcome after ACL reconstruction. The second aim was to use multivariate analysis to study the possible factors independently. METHODS: A cohort study was conducted with a follow-up of six months. Before surgery, patient variables were scored. Surgical variables were scored during arthroscopic ACL reconstructions with a single-bundle technique and hamstring autograft. The Lysholm score and subscales of the Knee Injury Osteoarthritis Outcome Score (KOOS) were assessed six months post surgery. A multiple analysis of variance (ANOVA) model was used to identify prognostic factors for outcome. RESULTS: In total, 118 patients were included. Patients, aged <=30years, with a subjective knee score >= six, with normal flexion range of motion (ROM) of the knee, with flexion and extension strength deficit of <=20%, and those with no previous knee surgery in the same knee at baseline scored significantly higher on outcome after multivariate analysis. No significant effect of surgical factors could be found. CONCLUSION: Younger age, higher subjective knee score, normal knee flexion, normal knee flexion and extension strength, and no previous knee surgery in the patients' history at baseline are associated with a more rapid recovery after ACL reconstruction. LEVEL OF EVIDENCE: Level III, prognostic study. PMID- 26260245 TI - Smart multifunctional drug delivery towards anticancer therapy harmonized in mesoporous nanoparticles. AB - Nanomedicine seeks to apply nanoscale materials for the therapy and diagnosis of diseased and damaged tissues. Recent advances in nanotechnology have made a major contribution to the development of multifunctional nanomaterials, which represents a paradigm shift from single purpose to multipurpose materials. Multifunctional nanomaterials have been proposed to enable simultaneous target imaging and on-demand delivery of therapeutic agents only to the specific site. Most advanced systems are also responsive to internal or external stimuli. This approach is particularly important for highly potent drugs (e.g. chemotherapeutics), which should be delivered in a discreet manner and interact with cells/tissues only locally. Both advances in imaging and precisely controlled and localized delivery are critically important in cancer treatment, and the use of such systems - theranostics - holds great promise to minimise side effects and boost therapeutic effectiveness of the treatment. Among others, mesoporous silica nanoparticles (MSNPs) are considered one of the most promising nanomaterials for drug delivery. Due to their unique intrinsic features, including tunable porosity and size, large surface area, structural diversity, easily modifiable chemistry and suitability for functionalization, and biocompatibility, MSNPs have been extensively utilized as multifunctional nanocarrier systems. The combination or hybridization with biomolecules, drugs, and other nanoparticles potentiated the ability of MSNPs towards multifunctionality, and even smart actions stimulated by specified signals, including pH, optical signal, redox reaction, electricity and magnetism. This paper provides a comprehensive review of the state-of-the-art of multifunctional, smart drug delivery systems centered on advanced MSNPs, with special emphasis on cancer related applications. PMID- 26260244 TI - Enhanced conversion of induced neuronal cells (iN cells) from human fibroblasts: Utility in uncovering cellular deficits in mental illness-associated chromosomal abnormalities. AB - The novel technology of induced neuronal cells (iN cells) is promising for translational neuroscience, as it allows the conversion of human fibroblasts into cells with postmitotic neuronal traits. However, a major technical barrier is the low conversion rate. To overcome this problem, we optimized the conversion media. Using our improved formulation, we studied how major mental illness-associated chromosomal abnormalities may impact the characteristics of iN cells. We demonstrated that our new iN cell culture protocol enabled us to obtain more precise measurement of neuronal cellular phenotypes than previous iN cell methods. Thus, this iN cell culture provides a platform to efficiently obtain possible cellular phenotypes caused by genetic differences, which can be more thoroughly studied in research using other human cell models such as induced pluripotent stem cells. PMID- 26260246 TI - Assessing the impact of a primary care electronic medical record system in three Kenyan rural health centers. AB - OBJECTIVE: Efficient, effective health care requires rapid availability of patient information. We designed, implemented, and assessed the impact of a primary care electronic medical record (EMR) in three rural Kenyan health centers. METHOD: Local clinicians identified data required for primary care and public health reporting. We designed paper encounter forms to capture these data in adult medicine, pediatric, and antenatal clinics. Encounter form data were hand-entered into a new primary care module in an existing EMR serving onsite clinics serving patients infected with the human immunodeficiency virus (HIV). Before subsequent visits, Summary Reports were printed containing selected patient data with reminders for needed HIV care. We assessed effects on patient flow and provider work with time-motion studies before implementation and two years later, and we surveyed providers' satisfaction with the EMR. RESULTS: Between September 2008 and December 2011, 72 635 primary care patients were registered and 114 480 encounter forms were completed. During 2011, 32 193 unique patients visited primary care clinics, and encounter forms were completed for all visits. Of 1031 (3.2%) who were HIV-infected, 85% received HIV care. Patient clinic time increased from 37 to 81 min/visit after EMR implementation in one health center and 56 to 106 min/visit in the other. However, outpatient visits to both health centers increased by 85%. Three-quarters of increased time was spent waiting. Despite nearly doubling visits, there was no change in clinical officers' work patterns, but the nurses' and the clerks' patient care time decreased after EMR implementation. Providers were generally satisfied with the EMR but desired additional training. CONCLUSIONS: We successfully implemented a primary care EMR in three rural Kenyan health centers. Patient waiting time was dramatically lengthened while the nurses' and the clerks' patient care time decreased. Long-term use of EMRs in such settings will require changes in culture and workflow. PMID- 26260247 TI - Design and feasibility of integrating personalized PRO dashboards into prostate cancer care. AB - OBJECTIVE: Patient-reported outcomes (PROs) are a valued source of health information, but prior work focuses largely on data capture without guidance on visual displays that promote effective PRO use in patient-centered care. We engaged patients, providers, and design experts in human-centered design of "PRO dashboards" that illustrate trends in health-related quality of life (HRQOL) reported by patients following prostate cancer treatment. MATERIALS AND METHODS: We designed and assessed the feasibility of integrating dashboards into care in 3 steps: (1) capture PRO needs of patients and providers through focus groups and interviews; (2) iteratively build and refine a prototype dashboard; and (3) pilot test dashboards with patients and their provider during follow-up care. RESULTS: Focus groups (n = 60 patients) prioritized needs for dashboards that compared longitudinal trends in patients' HRQOL with "men like me." Of the candidate dashboard designs, 50 patients and 50 providers rated pictographs less helpful than bar charts, line graphs, or tables (P < .001) and preferred bar charts and line graphs most. Given these needs and the design recommendations from our Patient Advisory Board (n = 7) and design experts (n = 7), we built and refined a prototype that charts patients' HRQOL compared with age- and treatment-matched patients in personalized dashboards. Pilot testing dashboard use (n = 12 patients) improved compliance with quality indicators for prostate cancer care (P < .01). CONCLUSION: PRO dashboards are a promising approach for integrating patient-generated data into prostate cancer care. Informed by human-centered design principles, this work establishes guidance on dashboard content, tailoring, and clinical use that patients and providers find meaningful. PMID- 26260248 TI - A three-dimensional large deformation model for soft tissue using meshless method. AB - BACKGROUND: Recently, a great number of studies have been carried out to model soft tissue deformation in contact with surgical instruments to aid the development of surgical simulators. Precise methods to model the soft tissue such as the Finite Element Method (FEM) lack accuracy in large deformations. METHODS: An innovative meshless method is used, which has high precision and is applicable to large deformations. The meshless simulation method is implemented for a 2D beam and a 3D cube. Experiments are conducted for two silicone-gel samples to verify the correctness of the method. RESULTS: The meshless results in 2D and 3D show better accuracy for large deformations in comparison with the FEM. This method is used to model human organs such as liver and gallbladder. CONCLUSION: It is concluded that the proposed model exhibits good accuracy as well as speed. Thus, it seems promising to be employed in surgical simulators. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26260250 TI - The development of implicit gender attitudes. AB - The development course of implicit and explicit gender attitudes between the ages of 5 and adulthood is investigated. Findings demonstrate that implicit and explicit own-gender preferences emerge early in both boys and girls, but implicit own-gender preferences are stronger in young girls than boys. In addition, female participants' attitudes remain largely stable over development, whereas male participants' implicit and explicit attitudes show an age-related shift towards increasing female positivity. Gender attitudes are an anomaly in that social evaluations dissociate from social status, with both male and female participants tending to evaluate female more positively than male. PMID- 26260249 TI - Caveolae regulate vasoconstriction of conduit arteries to angiotensin II in hindlimb unweighted rats. AB - Weightlessness induces the functional remodelling of arteries, but the changes to angiotensin II (Ang II)-elicited vasoconstriction and the underlying mechanism have never been reported. Caveolae are invaginations of the cell membrane crucial for the contraction of vascular smooth muscle cells, so we investigated the adaptation of Ang II-elicited vasoconstriction to simulated weightlessness and the role of caveolae in it. The 4 week hindlimb unweighted (HU) rat was used to simulate the effects of weightlessness. Ang II-elicited vasoconstriction was measured by isometric force recording. The morphology of caveolae was examined by transmission electron microscope. The binding of the angiotensin II type 1 receptor (AT1 ) and caveolin-1 (cav-1) was examined by coimmunoprecipitation and Western blot. We found that the maximal developing force (E(max)) of Ang II elicited vasoconstriction was decreased in abdominal aorta by 30.6%, unchanged in thoracic aorta and increased in carotid artery by 17.9% after HU, while EC50 of the response was increased in all three arteries (P < 0.05). AT1 desensitization upon activation was significantly reduced by HU in all three arteries, as was the number of caveolae (P < 0.05). Furthermore, Ang II promoted the binding of AT1 and cav-1 significantly in control but not HU arteries. Both the number of caveolae and the binding of AT1 and cav-1 in HU arteries were restored by cholesterol pretreatment which also reinstated the change in EC50 as well as the level of AT1 desensitization. These results indicate that modified caveolae in vascular smooth muscle cells could interfere with the binding of AT1 and cav-1 mediating the adaptation of Ang II-elicited vasoconstriction to HU. PMID- 26260251 TI - [Bi12Ni7(CO)4](4-): Aggregation of Intermetalloid Clusters by Their Thermal Deligation and Oxidation. AB - Reported are the synthesis and structure of the anionic intermetalloid cluster [Bi12Ni7(CO)4](4-). It was synthesized from the known smaller clusters Bi3Ni4(CO)6(3-), Bi3Ni6(CO)9(3-), and Ni@Bi6Ni6(CO)8(4-) by their aggregation as a result of thermal deligation and oxidation. The new cluster is structurally characterized by single-crystal X-ray diffraction in the compound (K[crypt])4[Bi12Ni7(CO)4] (1), and its presence in solution is confirmed by electrospray mass spectrometry. It can be viewed as composed of a Ni-centered icosahedral core of Bi6Ni6(CO)4 where two diametrically opposed Ni atoms are capped by Bi3 triangles. However, its electron count is rationalized based on a structure made of fused tetrahedra. PMID- 26260253 TI - Estimation of Age Using Alveolar Bone Loss: Forensic and Anthropological Applications. AB - The objective of this study was to utilize a new odontological methodological approach based on radiographic for age estimation. The study was comprised of 397 participants aged between 9 and 87 years. A clinical examination and a radiographic assessment of alveolar bone loss were performed. Direct measures of alveolar bone level were recorded using CT scans. A medical examination report was attached to the investigation file. Because of the link between alveolar bone loss and age, a model was proposed to enable simple, reliable, and quick age estimation. This work added new arguments for age estimation. This study aimed to develop a simple, standardized, and reproducible technique for age estimation of adults of actual populations in forensic medicine and ancient populations in funeral anthropology. PMID- 26260252 TI - Ethylglucuronide in maternal hair as a biomarker of prenatal alcohol exposure. AB - While direct ethanol metabolites, including ethylglucuronide (EtG), play an important role for the confirmation of prenatal alcohol exposure (PAE), their utility is often limited by their short half-lives in blood and urine. Maternal hair allows for a retrospective measure of PAE for up to several months. This study examined the validity of hair EtG (hEtG) relative to self-reporting and five other biomarkers in 85 pregnant women. Patients were recruited from a UNM prenatal clinic, which provides care to women with substance abuse and addiction disorders. The composite index, which was based on self-reported measures of alcohol use and allowed us to classify subjects into PAE (n = 42) and control (n = 43) groups, was the criterion measure used to estimate the sensitivity and specificity of hEtG. Proximal segments of hair were collected at enrollment (average 22.0 gestational weeks) and analyzed by LC-MS/MS. At the same visit, maternal blood and urine specimens were collected for analysis of GGT, %dCDT, PEth, uEtG, and uEtS. The study population included mostly opioid-dependent (80%) patients, a large proportion of ethnic minorities (75.3% Hispanic/Latina, 8.2% American Indian, 4.7% African-American), and patients with low education (48.2% < high school). The mean maternal age at enrollment was 26.7 +/- 4.8 years. Hair EtG demonstrated 19% sensitivity and 86% specificity. The sensitivities of other biomarkers were comparable (5-20%) to hEtG but specificities were higher (98 100%). Hair EtG sensitivity improved when combined with other biomarkers, especially with GGT (32.5%) and PEth (27.5%). In addition, validity of hEtG improved in patients with less frequent shampooing and those who did not use hair dyes/chemical treatments. These data suggest that hEtG alone is not a sufficiently sensitive or specific biomarker to be used separately for the identification of PAE, but might be useful in a battery along with other maternal biomarkers. PMID- 26260254 TI - Myotonia congenita: novel mutations in CLCN1 gene. AB - Myotonia congenita belongs to the group of non-dystrophic myotonia caused by mutations of CLCN1gene, which encodes human skeletal muscle chloride channel 1. It can be inherited either in autosomal dominant (Thomsen disease) or recessive (Becker disease) forms. Here we have sequenced all 23 exons and exon-intron boundaries of the CLCN1 gene, in a panel of 5 unrelated Chinese patients with myotonia congenita (2 with dominant and 3 with recessive form). In addition, detailed clinical analysis was performed in these patients to summarize their clinical characteristics in relation to their genotypes. Mutational analyses revealed 7 different point mutations. Of these, we have found 3 novel mutations including 2 missense (R47W, V229M), one splicing (IVS19+2T>C), and 4 known mutations (Y261C,G523D, M560T, G859D). Our data expand the spectrum of CLCN1 mutations and provide insights for genotype-phenotype correlations of myotonia congenita in the Chinese population. PMID- 26260255 TI - Sustained Reduction of Ventilator-Associated Pneumonia Rates Using Real-Time Course Correction With a Ventilator Bundle Compliance Dashboard. AB - BACKGROUND: The effectiveness of practice bundles on reducing ventilator associated pneumonia (VAP) has been questioned. OBJECTIVE: To implement a comprehensive program that included a real-time bundle compliance dashboard to improve compliance and reduce ventilator-associated complications. DESIGN Before and-after quasi-experimental study with interrupted time-series analysis. SETTING Academic medical center. METHODS: In 2007 a comprehensive institutional ventilator bundle program was developed. To assess bundle compliance and stimulate instant course correction of noncompliant parameters, a real-time computerized dashboard was developed. Program impact in 6 adult intensive care units (ICUs) was assessed. Bundle compliance was noted as an overall cumulative bundle adherence assessment, reflecting the percentage of time all elements were concurrently in compliance for all patients. RESULTS: The VAP rate in all ICUs combined decreased from 19.5 to 9.2 VAPs per 1,000 ventilator-days following program implementation (P<.001). Bundle compliance significantly increased (Z100 score of 23% in August 2007 to 83% in June 2011 [P<.001]). The implementation resulted in a significant monthly decrease in the overall ICU VAP rate of 3.28/1,000 ventilator-days (95% CI, 2.64-3.92/1,000 ventilator-days). Following the intervention, the VAP rate decreased significantly at a rate of 0.20/1,000 ventilator-days per month (95% CI, 0.14-0.30/1,000 ventilator-days per month). Among all adult ICUs combined, improved bundle compliance was moderately correlated with monthly VAP rate reductions (Pearson correlation coefficient, 0.32). CONCLUSION: A prevention program using a real-time bundle adherence dashboard was associated with significant sustained decreases in VAP rates and an increase in bundle compliance among adult ICU patients. PMID- 26260256 TI - Burdensome problems of chronic musculoskeletal pain and future prospects. AB - According to a recent survey, about 15 % of the Japanese population suffers from moderate-severe chronic musculoskeletal pain persisting for at least 6 months. Social factors and related psychological factors (including depression) thus appear to greatly affect chronic musculoskeletal pain. This suggests the need for measures that take these factors into account. Treatment for musculoskeletal pain at present is generally based on a biomedical model that has been used for many years in this field, and modern medical imaging technologies have been a high priority to support this model and treatment strategy. Under the concept of the biomedical model, nonsteroidal antiinflammatory drugs, channel blockers and opioid analgesics are generally used as pharmacotherapy to alleviate chronic pain. However, these drugs are commonly associated with problems such as adverse effects, drug dependency and drug abuse, and they must be used with care. Surgery may also be effective in treating certain diseases, but studies have shown that many patients suffer residual chronic pain even after such treatment. Besides, exercise therapy has been found to be effective in treating many different types of chronic pain. Lately, various countries have been launching interdisciplinary pain centers that use a multidisciplinary approach to treat chronic musculoskeletal pain. Treatment in these centers is provided by a team of specialists in anesthesiology, psychiatry and orthopedics as well as the relevant paramedical professionals. The therapeutic strategy is based on a cognitive behavioral approach, and patients are taught about methods for restoring physical function and coping with pain, mostly with drugs and exercise therapy, so that any pain present does not impair function and the patient can reintegrate into society. PMID- 26260257 TI - Effect of simultaneous stretching of the wrist and finger extensors for lateral epicondylitis: a gross anatomical study of the tendinous origins of the extensor carpi radialis brevis and extensor digitorum communis. AB - BACKGROUND: Pulling the wrist into flexion with the elbow in extension and forearm in pronation has been used as the stretching technique of wrist extensors for lateral epicondylitis. Simultaneous stretching of the fingers in addition to the wrist flexion has also been applied. However, the mechanism of this simultaneous stretching has not been clarified. This study is designed to clarify the mechanism underlying this simultaneous stretching technique based on the anatomical features of the origins of the extensor carpi radialis brevis (ECRB) and extensor digitorum communis (EDC). METHODS: Thirty-nine arms from formalin embalmed Japanese human specimens were dissected. The features of the origins of the ECRB and EDC were macroscopically observed, and the locations of each origin on the lateral epicondyle were measured. RESULTS: The ECRB had a long and wide, purely tendinous origin which originated from the anterior slope of the lateral epicondyle. The tendinous origin of the index finger of the EDC (EDC-IF) arose from the posterior aspect of the ECRB tendinous origin, with a coexisting muscular portion observed at the level of the proximal forearm. The middle finger of the EDC (EDC-MF) had a short tendinous origin with an associated muscular portion and originated proximo-laterally to the origin of the ECRB on the lateral epicondyle. In addition, the muscular origin of the EDC-MF arose on the superficial and posterior aspect of the ECRB tendinous origin. In contrast, the ring and little fingers of the EDC originated from the tendinous septum of the extensor digiti minimi and extensor carpi ulnaris, and had no connection with the ECRB tendinous origin. CONCLUSIONS: On the basis of our anatomical findings, simultaneous stretching of the wrist extensors by wrist, index and middle fingers flexion could provide stretching force to both the tendinous origins of the ECRB and EDC through the EDC-IF and EDC-MF. PMID- 26260258 TI - Guggulsterone Attenuated Lipopolysaccharide-Induced Inflammatory Responses in Mouse Inner Medullary Collecting Duct-3 Cells. AB - Guggulsterone (GS) is a phytosterol that has been used to treat inflammatory diseases such as colitis, obesity, and thrombosis. Although many previous studies have examined activities of GS, the effect of GS on lipopolysaccharide (LPS) induced inflammatory responses in mouse inner medullary collecting duct-3 (mIMCD 3) cells have not been examined. Therefore, here, we investigated the anti inflammatory action of GS on mIMCD-3 cells exposed to LPS. LPS treatment on mIMCD 3 cells produced pro-inflammatory molecules such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) significantly; however, GS treatment significantly inhibited the production of pro-inflammatory molecules. In addition, GS inhibited the degradation of Ikappa-Balpha and translocation of NF kappaB on mIMCD-3 cells. These results suggest that GS could inhibit inflammatory responses in collecting duct cells which could contribute to kidney injury during systemic infection. PMID- 26260260 TI - Synthetic biology: UBER - a portable system for cross-species genetic engineering. PMID- 26260259 TI - Differential antitumor effects of vitamin D analogues on colorectal carcinoma in culture. AB - Colorectal cancer (CRC) is an emerging global problem with the rapid increase in its incidence being associated with an unhealthy lifestyle. Epidemiological studies have shown that decreased levels of vitamin D3 significantly increases the risk of CRC. Furthermore, negative effects of vitamin D3 deficiency can be compensated by appropriate supplementation. Vitamin D3 was shown to inhibit growth and induce differentiation of cancer cells, however, excessive vitamin D3 intake leads to hypercalcemia. Thus, development of efficient vitamin D3 analogues with limited impact on calcium homeostasis is an important scientific and clinically relevant task. The aims of the present study were to compare the antiproliferative potential of classic vitamin D3 metabolites (1alpha,25(OH)2D3 and 25(OH)D3) with selected low calcemic analogues (calcipotriol and 20(OH)D3) on CRC cell lines and to investigate the expression of vitamin D-related genes in CRC cell lines and clinical samples. Vitamin D3 analogues exerted anti proliferative effects on all CRC cell lines tested. Calcipotriol proved to be as potent as 1alpha,25(OH)2D3 and had more efficacy than 20-hydroxyvitamin D3. In addition, the analogs tested effectively inhibited the formation of colonies in Matrigel. The expression of genes involved in 1alpha,25(OH)2D3 signaling and metabolism varied in cell lines analysed, which explains in part their different sensitivities to the various analogues. In CRC biopsies, there was decreased VDR expression in tumor samples in comparison to the surgical margin and healthy colon samples (p<0.01). The present study indicates that vitamin D3 analogues which have low calcemic activity, such as calcipotriol or 20(OH)D3, are very promising candidates for CRC therapy. Moreover, expression profiling of vitamin D related genes is likely to be a powerful tool in the planning of anticancer therapy. Decreased levels of VDR and increased CYP24A1 expression in clinical samples underline the importance of deregulation of vitamin D pathways in the development of CRC. PMID- 26260263 TI - Adaptive quantum computation in changing environments using projective simulation. AB - Quantum information processing devices need to be robust and stable against external noise and internal imperfections to ensure correct operation. In a setting of measurement-based quantum computation, we explore how an intelligent agent endowed with a projective simulator can act as controller to adapt measurement directions to an external stray field of unknown magnitude in a fixed direction. We assess the agent's learning behavior in static and time-varying fields and explore composition strategies in the projective simulator to improve the agent's performance. We demonstrate the applicability by correcting for stray fields in a measurement-based algorithm for Grover's search. Thereby, we lay out a path for adaptive controllers based on intelligent agents for quantum information tasks. PMID- 26260261 TI - Augmented genetic decoding: global, local and temporal alterations of decoding processes and codon meaning. AB - The non-universality of the genetic code is now widely appreciated. Codes differ between organisms, and certain genes are known to alter the decoding rules in a site-specific manner. Recently discovered examples of decoding plasticity are particularly spectacular. These examples include organisms and organelles with disruptions of triplet continuity during the translation of many genes, viruses that alter the entire genetic code of their hosts and organisms that adjust their genetic code in response to changing environments. In this Review, we outline various modes of alternative genetic decoding and expand existing terminology to accommodate recently discovered manifestations of this seemingly sophisticated phenomenon. PMID- 26260262 TI - Genomes by design. AB - Next-generation DNA sequencing has revealed the complete genome sequences of numerous organisms, establishing a fundamental and growing understanding of genetic variation and phenotypic diversity. Engineering at the gene, network and whole-genome scale aims to introduce targeted genetic changes both to explore emergent phenotypes and to introduce new functionalities. Expansion of these approaches into massively parallel platforms establishes the ability to generate targeted genome modifications, elucidating causal links between genotype and phenotype, as well as the ability to design and reprogramme organisms. In this Review, we explore techniques and applications in genome engineering, outlining key advances and defining challenges. PMID- 26260264 TI - Non-suicidal self-injury among Dutch and Belgian adolescents: Personality, stress and coping. AB - BACKGROUND: This study examines: (1) the prevalence of Non-Suicidal Self-Injury (NSSI) among Dutch and Belgian adolescents, (2) the associations between Big Five personality traits and NSSI engagement/versatility (i.e., number of NSSI methods), and (3) whether these associations are mediated by perceived stress and coping. METHODS: A total of 946 Flemish (46%) and Dutch (54%) non institutionalized adolescents (Mean age=15.52; SD=1.34, 44% females) were surveyed. Measures included the NSSI subscale of the Self-Harm-Inventory, the Dutch Quick Big Five Personality questionnaire, the Perceived Stress Scale and the Utrecht Coping List for Adolescents. Examination of zero-order correlations was used to reveal associations, and hierarchical regression analysis was used to reveal potential mediators which were further examined within parallel mediation models by using a bootstrapping-corrected procedure. RESULTS: Lifetime prevalence of NSSI was 24.31%. Neuroticism; perceived stress; and distractive, avoidant, depressive, and emotional coping were positively associated with NSSI engagement, whereas Agreeableness, Conscientiousness; and active, social, and optimistic coping were negatively associated with NSSI engagement. Observed relationships between personality traits and NSSI engagement were consistently explained by perceived stress and depressive coping. A higher versatility of NSSI was not associated with any Big Five personality trait, but was associated with higher scores on perceived stress and depressive coping and with lower scores on active and optimistic coping. CONCLUSION: Our study suggests that a specific personality constellation is associated with NSSI engagement via high stress levels and a typical depressive reaction pattern to handle stressful life events. PMID- 26260265 TI - [Consensus on competencies for advanced nursing practice in Spain]. AB - INTRODUCTION: There is a lack of international consensus on the exact definition and core competencies of advanced practice nursing (APN) roles, a problem particularly acute in our national context due to the lack of APN role development, which has a significantly short history in our country. The main objective of this paper was the delineation of the competence framework for Advanced Practice Nurses in our national context based on expert consensus through the Delphi method METHOD: Based on a preliminary literature review process, a conglomerate of 17 domains of competence (clusters of related competencies) were identified. This initial set was revised, refined and validated by a group of expert panellists on the subject (clinicians, researchers, managers, and teachers) through successive rounds in search of a suitable consensus on each of the various proposed items RESULTS: The results helped to establish a solid foundation in the form of a skills map that could identify those sets of more specific competencies for advanced practice roles, regardless of regulatory and professional practice context, identifying domains such as Research and Evidence Based Practice, Clinical and Professional Leadership, or Care Management DISCUSSION: This set of skills related to advanced practice roles in our environment can delineate competency standards common to this level of nursing practice, and serve as a reference for policy development, a review of roles, or the establishment of academic profiles. PMID- 26260266 TI - General synthesis of 2,1-benzisoxazoles (anthranils) from nitroarenes and benzylic C-H acids in aprotic media promoted by combination of strong bases and silylating agents. AB - Carbanions of phenylacetonitriles, benzyl sulfones, and dialkyl benzylphosphonates add nitroarenes at the ortho-position to the nitro group to form [Formula: see text]-adducts that, upon treatment with trialkylchlorosilane and additional base (t-BuOK or DBU), transform into 3-aryl-2,1-benzisoxazoles in moderate-to-good yields. PMID- 26260268 TI - Finite element modelling approaches for well-ordered porous metallic materials for orthopaedic applications: cost effectiveness and geometrical considerations. AB - The mechanical properties of well-ordered porous materials are related to their geometrical parameters at the mesoscale. Finite element (FE) analysis is a powerful tool to design well-ordered porous materials by analysing the mechanical behaviour. However, FE models are often computationally expensive. This article aims to develop a cost-effective FE model to simulate well-ordered porous metallic materials for orthopaedic applications. Solid and beam FE modelling approaches are compared, using finite size and infinite media models considering cubic unit cell geometry. The model is then applied to compare two unit cell geometries: cubic and diamond. Models having finite size provide similar results than the infinite media model approach for large sample sizes. In addition, these finite size models also capture the influence of the boundary conditions on the mechanical response for small sample sizes. The beam FE modelling approach showed little computational cost and similar results to the solid FE modelling approach. Diamond unit cell geometry appeared to be more suitable for orthopaedic applications than the cubic unit cell geometry. PMID- 26260267 TI - Re2O7-catalyzed formal [3 + 2] cycloaddition for diverse naphtho[1,2-b]furan-3 carboxamides and their biological evaluation. AB - Diverse naphtho[1,2-b]furan-3-carboxamide derivatives 12a-12q were synthesized in high yield via the novel Re2O7-catalyzed formal [3 + 2] cycloaddition of 1,4 naphthoquinones with beta-ketoamides as the key step. This methodology offers several advantages, such as environmentally benign character, the use of a mild catalyst, high yields, and ease of handling. The synthesized compounds were screened for their tyrosinase inhibitory, antioxidant, and antibacterial activities. The results showed that compound 12c exhibited excellent tyrosinase inhibitory activity with an IC50 of 13.48 MUg/mL, which is comparable to that of kojic acid (IC50 = 19.45 MUg/mL). Compounds 12a, 12b, and 12i displayed moderate antioxidant activities in a DPPH assay. Compound 12m showed good activity against S. aureus (MIC = 16 MUg/mL), and compound 12p was found to be active against E. coli (MIC = 16 MUg/mL). PMID- 26260269 TI - Comparative study of multi-enzyme production from typical agro-industrial residues and ultrasound-assisted extraction of crude enzyme in fermentation with Aspergillus japonicus PJ01. AB - Submerged fermentation (SmF) and solid-state fermentation (SSF) of Aspergillus japonicus PJ01 for multi-enzyme complexes (MEC) production were comparatively studied. The results showed that orange peel and wheat bran were the best substrates for MEC production in SmF and SSF, respectively. After 72 h of cultivation under SmF, the maximal pectinase, CMCase, and xylanase activities reached 2610, 85, and 335 U/gds (units/gram dry substrate), respectively; while after 72 h of cultivation under SSF, these three enzymes' activities reached 966, 58, and 1004 U/gds, respectively. Effects of ultrasound on extraction of crude enzymes from SSF medium were determined, the maximal activities of pectinase, CMCase, and xylanase increased to 1.20, 1.48, and 1.30-fold, respectively. Apparent different mycelia growths of SSF and SmF were observed by scanning electron microscopy; and different isoforms of the crude enzyme extracts from SSF and SmF were presented by zymogram analysis. PMID- 26260270 TI - Chimpanzee susceptibility to hepatitis C virus infection correlates with presence of Pt-KIR3DS2 and Pt-KIR2DL9: paired activating and inhibitory natural killer cell receptors. AB - Infection of humans and chimpanzees with Hepatitis C virus (HCV) results in either the resolution of the acute infection or its progression to a persistent infection associated with chronic liver disease. In cohorts of human patients, resolution of HCV infection has been associated with homozygosity for both C1(+)HLA-C and its cognate inhibitory receptor, KIR2DL3. Compared here are the killer cell immunoglobulin-like receptors (KIR) and major histocompatibility complex (MHC) class I factors of chimpanzees who resolve, or resist, HCV infection with those chimpanzees who progress to chronic infection. Analysis of Pt-KIR gene content diversity associated two of the 12 Pt-KIR with clinical outcome. Activating Pt-KIR3DS2 and inhibitory Pt-KIR2DL9 are strong receptors specific for the C2 epitope. They are encoded by neighboring genes within the Pt KIR locus that are in strong linkage disequilibrium. HCV-infected chimpanzees with KIR genotypes containing Pt-KIR3DS2 and KIR2DL9 are significantly more likely to progress to chronic infection than infected chimpanzees lacking the genes (p = 0.0123 and p = 0.0045, respectively), whereas human HLA-B allotypes having the C1 epitope are unusual, such allotypes comprise about one quarter of the chimpanzee Patr-B allotypes. Homozygous C1 (+) Patr-B are enriched in chimpanzees with chronic HCV infection, and the compound genotype of homozygous C1 (+) Patr-B combined with either Pt-KIR3DS2 or Pt-KIR2DL9 is more strongly associated with disease progression than either factor alone (p = 0.0031 and p = 0.0013, respectively). Thus, despite similarities suggesting a common basis in disease resistance, there are substantial differences in the KIR and MHC class I correlations observed for HCV-infected humans and chimpanzees, consistent with the divergence of their KIR and MHC class I systems. PMID- 26260271 TI - Phenylbutyrate-a pan-HDAC inhibitor-suppresses proliferation of glioblastoma LN 229 cell line. AB - Phenylbutyrate (PBA) is a histone deacetylase inhibitor known for inducing differentiation, cell cycle arrest, and apoptosis in various cancer cells. However, the effects of PBA seem to be very cell-type-specific and sometimes limited exclusively to a particular cell line. Here, we provided novel information concerning cellular effects of PBA in LN-229 and LN-18 glioblastoma cell lines which have not been previously evaluated in context of PBA exposure. We found that LN-18 cells were PBA-insensitive even at high concentrations of PBA. In contrary, in LN-229 cells, 5 and 15 mmol/L PBA inhibited cell growth and proliferation mainly by causing prominent changes in cell morphology and promoting S- and G2/M-dependent cell cycle arrest. Moreover, we observed nearly a 3-fold increase in apoptosis of LN-229 cells treated with 15 mmol/L PBA, in comparison to control. Furthermore, PBA was found to up-regulate the expression of p21 whereas p53 expression level remained unchanged. We also showed that PBA down-regulated the expression of the anti-apoptotic genes Bcl-2/Bcl-X L , however without affecting the expression of pro-apoptotic Bax and Bim. Taken together, our results suggest that PBA might potentially be considered as an agent slowing down the progress of glioblastoma; however, further analyses are still needed to comprehensively resolve the nature of its activity in this type of cancer. PMID- 26260272 TI - Glutathione S-transferase P1 gene rs4147581 polymorphism predicts overall survival of patients with hepatocellular carcinoma: evidence from an enlarged study. AB - As the most important detoxifying enzymes in liver, glutathione S-transferases (GSTs) can protect hepatocytes against carcinogens. We conducted a large cohort study to investigate the prognostic value of single nucleotide polymorphisms (SNPs) in seven encoding genes of GSTs for hepatocellular carcinoma (HCC). Twelve SNPs were genotyped and correlated with overall survival in 469 HCC patients. The median follow-up time of all patients was 21 (range 3-60) months, and the median survival time was 22 months. By the end of the study, 135 (28.8 %) patients were alive. Only rs4147581 in GSTP1 gene exhibited a significant association with survival of HCC patients (P = 0.006), with its mutant allele bearing a significantly lower risk of death (hazard ratio, 0.71; 95 % confidence interval 0.53-0.90), compared with the homozygous wide-type. A longer median survival time in patients with rs4147581 mutant allele was noticed than those homozygous wide type (P = 0.03), and there was a marked adverse effect on survival conferred by smoking exposure in these patients. Conclusively, our findings provide supporting evidence for a contributory role of GSTP1 rs4147581 polymorphism in predicting the prognosis of HCC. PMID- 26260273 TI - The critical role of quercetin in autophagy and apoptosis in HeLa cells. AB - In recent years, the effects of quercetin on autophagy and apoptosis of cancer cells have been widely reported, while effects on HeLa cells are still unclear. Here, HeLa cells were subjected to quercetin treatment, and then proliferation, apoptosis, and autophagy were evaluated using MTT, flow cytometry, and MDC staining, respectively. The LC3-I/II, Beclin 1, active caspase-3, and S6K1 phosphorylation were detected using Western blot assay. The ultrastructure of HeLa was observed via transmission electron microscope (TEM). Our findings showed that quercetin can dose-dependently inhibit the growth of HeLa cells. The MDC fluorescence was enhanced with increased concentration of quercetin and hit a plateau at 50 MUmol/l. Western blot assay revealed that LC3-I/II ratio, Beclin 1, and active caspase-3 protein were enforced in a dose-dependent method. However, the phosphorylation of S6K1 gradually decreased, concomitant with an increase of autophagy. In addition, TEM revealed that the number of autophagic vacuoles was peaked at 50 MUmol/l of quercetin. Besides, interference of autophagy with 3-MA led to proliferation inhibition and increased apoptosis in HeLa cells, accompanied by the decreased LC3-I/II conversion and the increased active caspase 3. In conclusion, quercetin can inhibit HeLa cell proliferation and induce protective autophagy at low concentrations; thus, 3-MA plus quercetin would suppress autophagy and effectively increased apoptosis. PMID- 26260274 TI - Probe current determination in analytical TEM/STEM and its application to the characterization of large area EDS detectors. AB - A simple procedure, which enables accurate measurement of transmission electron microscopy (TEM)/STEM probe currents using an energy loss spectrometer drift tube is described. The currents obtained are compared with those measured on the fluorescent screen to enable the losses due to secondary and backscattered electrons to be determined. The current values obtained from the drift tube allow the correction of fluorescent screen current densities to yield true current. They also enable CCD conversion efficiencies to be obtained, which in turn allows images to be calibrated in terms of electron fluence. Using probes of known current in conjunction with a NiO reference specimen enables the X-ray detector solid angle to be determined. The NiO specimen also allows a wide range of other EDS detector parameters to be obtained, including the presence of ice and carbon contamination. A range of performance characteristics are reported for two large area EDS detector systems. Many of the measurements reported herein have been automated via the use of freely available scripts for DigitalMicrograph. PMID- 26260275 TI - [Not Available]. PMID- 26260276 TI - Polymeric stabilizers for protection of soil and ground against wind and water erosion. AB - The article is devoted to the design, development and application of a new generation of binders for various dispersed systems, including soil, ground, sand, waste rock and others. The binders are formed by interaction of oppositely charged polyelectrolytes, both chemically stable and (bio)degradable. The fundamental aspects of interpolyelectrolyte reactions are discussed; the IPC structure and properties of the resulting interpolyelectrolyte complexes (IPCs) allow considering them as unique and universal binders. Numerous results of laboratory experiments and field trials of the IPC formulations are presented. In particular, large-scale tests have been done in the Chernobyl accident zone where the IPC binders were shown to be effective means to suppress water and wind erosion thereby preventing a spread of radioactive particles (radionuclides) from contaminated sites. Ecologically friendly IPC compositions are described, including those based on commercially available polymers; prospects for improving their efficiency and extending the range of their possible use are discussed. PMID- 26260277 TI - Concussion in Chronic Traumatic Encephalopathy. AB - Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that occurs in association with repetitive mild traumatic brain injury. It is associated with a variety of clinical symptoms in multiple domains, and there is a distinct pattern of pathological changes. The abnormal tau pathology in CTE occurs uniquely in those regions of the brain that are likely most susceptible to stress concentration during trauma. CTE has been associated with a variety of types of repetitive head trauma, most frequently contact sports. In cases published to date, the mean length of exposure to repetitive head trauma was 15.4 years. The clinical symptoms of the disease began after a mean latency of 14.5 years with a mean age of death of 59.3 years. Most subjects had a reported history of concussions with a mean of 20.3. However, 16 % of published CTE subjects did not have a history of concussion suggesting that subconcussive hits are sufficient to lead to the development of CTE. Overall, the number of years of exposure, not the number of concussions, was significantly associated with worse tau pathology in CTE. This suggests that it is the chronic and repetitive nature of head trauma, irrespective of concussive symptoms, that is the most important driver of disease. CTE and exposure to repetitive head trauma is also associated with a variety of other neurodegenerations, including Alzheimer disease. In fact, amyloid beta peptide deposition is altered and accelerated in CTE and is associated with worse disease. Here, we review the current exposure, clinical, and pathological associations of CTE. PMID- 26260278 TI - Risk-Benefit Profile of Gastric vs Transpyloric Feeding in Mechanically Ventilated Patients: A Meta-Analysis. AB - BACKGROUND: The risk-benefit profile of transpyloric vs gastric feeding in mechanically ventilated (MV) patients has not been definitively established. OBJECTIVE: To evaluate the risks and benefits of transpyloric feeding compared with gastric feeding in mechanically ventilated patients. DESIGN: We systematically searched MEDLINE, Google Scholar, EMBASE, and the Cochrane Central Register of Controlled Trials databases for eligible articles through June 21, 2013. Randomized controlled trials (RCTs) that reported a comparison between gastric and transpyloric feeding in MV patients were selected. Two reviewers independently extracted data on populations, methods, outcomes, and risk of bias. Ventilator-associated pneumonia (VAP) was considered the primary outcome. RESULTS: A total of 8 RCTs, including 835 MV patients, were identified and analyzed. Our pooled findings indicated that there was a significant reduction in VAP through transpyloric feeding compared with gastric feeding (relative risk [RR], 0.67; 95% confidence interval [CI], 0.53 to 0.85; P = .001) but not in mortality (RR, 1.08; 95% CI, 0.86 to 1.36; P = .49), length of mechanical ventilation (mean difference [MD], -0.16; 95% CI, -0.75 to 0.43; P = .59), length of stay in the intensive care unit (MD, -0.91; 95% CI, -2.75 to 0.94; P = .34), incidence of diarrhea (RR, 0.9; 95% CI, 0.66 to 1.23; P = .50), and incidence of vomiting (RR, 0.82; 95% CI, 0.25 to 2.72; P = .75). CONCLUSIONS: Transpyloric feeding in MV adults was associated with significantly less incidence of VAP compared with gastric feeding. No differences were observed in other outcomes, suggesting that the difference observed in the incidence of VAP may be spurious and needs confirmation. PMID- 26260279 TI - Correlates of weight stigma in adults with overweight and obesity: A systematic literature review. AB - OBJECTIVE: While evidence regarding associations between weight stigma and biopsychosocial outcomes is accumulating, outcomes are considered in isolation. Thus, little is known about their complex relationships. This article extends existing work by systematically reviewing the biopsychosocial consequences of stigma in adults with overweight/obesity. METHODS: Articles were identified through Medline, CINAHL, PsycINFO, Embase, Web of Science, and Cochrane databases. Independent extraction of articles was conducted using predefined data fields, including data on biopsychosocial correlates in each study. RESULTS: Twenty-three studies published from 2001 and addressing correlates of stigma in adults with overweight/obesity (body mass index >=25 kg m(-2); 18-65 years) were identified. Numerous biopsychosocial correlates of weight stigma were studied, particularly in treatment-seeking individuals. Available research shows that weight stigma is consistently associated with medication non-adherence, mental health, anxiety, perceived stress, antisocial behavior, substance use, coping strategies, and social support. Biopsychosocial correlates were not considered in combination in research. Psychological correlates were well documented in comparison to biological and social correlates for each weight stigma type. There were some indications that associations are stronger once stigma is internalized. CONCLUSIONS: While there is evidence for biopsychosocial correlates of weight stigma, these are not considered in combination in research; thus their inter relationships are unknown. Conclusions from the review are limited by this and the small number of studies, types of designs, and variables considered. PMID- 26260280 TI - Ability of Bottle Cap Color to Facilitate Accurate Patient-Physician Communication Regarding Medication Identity in Patients with Glaucoma. AB - PURPOSE: To determine the accuracy of patient-physician communication regarding topical ophthalmic medication use based on bottle cap color, particularly among individuals who may have acquired color vision deficiency from glaucoma. DESIGN: Cross-sectional, clinical study. PARTICIPANTS: Patients aged >=18 years with primary open-angle, primary angle-closure, pseudoexfoliation, or pigment dispersion glaucoma, bilateral visual acuity of >=20/400, and no concurrent conditions that may affect color vision. METHODS: A total of 100 patients provided color descriptions of 11 distinct medication bottle caps. Color descriptors were then presented to 3 physicians. Physicians matched each color descriptor to the medication they thought the descriptor was describing. MAIN OUTCOME MEASURES: Frequency of patient-physician agreement, occurring when all 3 physicians accurately matched the color descriptor to the correct medication. Multivariate regression models evaluated whether patient-physician agreement decreased with degree of better-eye visual field (VF) damage, color descriptor heterogeneity, or color vision deficiency, as determined by the Hardy-Rand Rittler (HRR) score and Lanthony D15 color confusion index (D15 CCI). RESULTS: Subjects had a mean age of 69 (+/-11) years, with VF mean deviation of -4.7 (+/ 6.0) and -10.9 (+/-8.4) decibels (dB) in the better- and worse-seeing eyes, respectively. Patients produced 102 unique color descriptors to describe the colors of the 11 bottle caps. Among individual patients, the mean number of medications demonstrating agreement was 6.1/11 (55.5%). Agreement was less than 15% for 4 medications (prednisolone acetate [generic], betaxolol HCl [Betoptic; Alcon Laboratories Inc., Fort Worth, TX], brinzolamide/brimonidine [Simbrinza; Alcon Laboratories Inc.], and latanoprost [Xalatan; Pfizer, Inc., New York, NY]). Lower HRR scores and higher D15 CCI (both indicating worse color vision) were associated with greater VF damage (P < 0.001). Extent of color vision deficiency and color descriptor heterogeneity significantly predicted agreement in multivariate models (odds of agreement = 0.90 per 1 point decrement in HRR score, P < 0.001; odds of agreement = 0.30 for medications exhibiting high heterogeneity [>=11 descriptors], P = 0.007). CONCLUSIONS: Physician understanding of patient medication use based solely on bottle cap color is frequently incorrect, particularly in patients with glaucoma who may have color vision deficiency. Errors based on communication using bottle cap color alone may be common and could lead to confusion and harm. PMID- 26260281 TI - The Association of Refractive Error with Glaucoma in a Multiethnic Population. AB - PURPOSE: To evaluate the association between refractive error and the prevalence of glaucoma by race or ethnicity. DESIGN: Cross-sectional study. PARTICIPANTS: Kaiser Permanente Northern California Health Plan members with refractive error measured at 35 years of age or older between 2008 and 2014 and with no history of cataract surgery, refractive surgery, or a corneal disorder. METHODS: We identified 34 040 members with glaucoma or ocular hypertension (OHTN; cases) and 403 398 members without glaucoma (controls). Glaucoma cases were classified as primary angle-closure glaucoma (PACG); 1 of the 4 forms of open-angle glaucoma: primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), pigmentary glaucoma (PIGM), and pseudoexfoliation glaucoma (PEX); or OHTN. Refractive error, expressed as spherical equivalent (SE), was coded as a continuous trait and also as categories. Logistic regression analyses were used to estimate the association between refractive error and the prevalence of glaucoma overall and in specific racial or ethnic groups. MAIN OUTCOME MEASURES: The association between refractive error and glaucoma subtypes evaluated as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: In controls, the mean SE was -0.59 diopters (D) (standard deviation, 2.62 D). Each 1-D reduction in SE was associated with a 22% decrease in the odds of PACG (OR, 0.78; 95% CI, 0.77-0.80) and with increases in the odds of open-angle glaucoma ranging from 1.23 (95% CI, 1.20-1.26) for PIGM, to 1.07 (95% CI, 1.03-1.11) for PEX, and to 1.05 (95% CI, 1.04-1.06) for OHTN. In addition, we observed a stronger association between myopia and POAG among non-Hispanic whites (OR, 1.12; 95% CI, 1.11-1.13) and NTG among Asians (OR, 1.17; 95% CI, 1.15-1.20) and non-Hispanic whites (OR, 1.19; 95% CI, 1.15-1.22). CONCLUSIONS: Myopia was associated with an increased prevalence of all forms of open-angle glaucoma and OHTN, whereas hyperopia was associated with a substantially increased prevalence of PACG. Although high myopia is a strong risk factor for glaucoma subtypes, low and moderate myopia also have a significant effect on glaucoma risk. Additionally, there were moderate racial differences in the association of myopia with the risk of POAG and NTG. PMID- 26260282 TI - Tumor-related markers in histologically normal margins correlate with locally recurrent oral squamous cell carcinoma: a retrospective study. AB - BACKGROUND: Oral squamous cell carcinoma (OSCC) is characterized by a high rate of local recurrence (LR) even when the surgical margins are considered histopathologically 'normal'. The aim of our study was to determine the relationship between early tumor-related markers detected in histologically normal margins (HNM) and LR as well as disease-free survival in OSCC. METHODS: The loss of heterozygosity (LOH) of markers on 9p21 (D9s1747, RPS6, D9s162) and 17p13 (TP53) and the immunostaining results of the corresponding mutant P53, P14, P15, and P16 proteins were assessed and correlated with LR and disease-free survival in 71 OSCC patients who had HNM. RESULTS: Fifteen of 71 patients with HNM developed LR. The presence of the following molecular markers in surgical margins was significantly correlated with the development of LR: LOH on chromosome 9p21 (D9s1747 + RPS6 + D9s162), any LOH, P16, and P53 (chi-square test, P < 0.05). The presence of TP53 LOH, 9p21 LOH, any LOH, P15, P16, P53, P16 + D9s1747, and P53 + TP53 had a significant effect on LR (Kaplan-Meier analysis, P < 0.05). P16 + D9s1747 was the most predictive factor using multivariate Cox analyses. CONCLUSIONS: Detection of tumor-related markers in histologically 'normal' resection margins may be a useful method for assessing LR in OSCC patients. PMID- 26260284 TI - [Not Available]. PMID- 26260283 TI - [Not Available]. PMID- 26260285 TI - [Not Available]. PMID- 26260286 TI - Bioprosthetic mesh reinforcement during temporary stoma closure decreases the rate of incisional hernia: A blinded, case-matched study in 94 patients with rectal cancer. AB - BACKGROUND: This case-matched study aimed to assess the feasibility and the potential benefits of placement of a prophylactic bioprosthetic collagen porcine mesh during closure of the temporary ileostomy after total mesorectal excision (TME) for rectal cancer. METHODS: From September 2012 to March 2013, 30 consecutive patients underwent placement of a retromuscular bioprosthetic mesh in the abdominal wall during closure of a diverting ileostomy after sphincter-saving laparoscopic TME for rectal cancer (mesh group). These 30 patients were matched individually to all identical patients who underwent a closure of the ileostomy without mesh after laparoscopic TME extracted from our prospective database (control group). The matching process was performed according to sex, age, body mass index, medically treated diabetes mellitus, neoadjuvant radiotherapy, and the delay between TME and closure of the ileostomy. The primary endpoint was stoma site incisional hernia, assessed in a blinded fashion by CT 1 year later. RESULTS: Mesh placement was feasible in all mesh group patients. There was no postoperative mortality. Overall postoperative morbidity rates were similar between mesh and control groups (n = 5 [17%] vs n = 7 [11%], respectively; P = .512). On the 1-year CT, incisional hernia at the site of stomal closure was less in the mesh group (n = 1) compared with the control group (n = 12; P = .043). Reoperation for incisional hernia at the site of stomal closure was performed in 8 patients (13%) in the control group, whereas no patient from the mesh group required repair of the hernia (P = .052). CONCLUSION: Placement of a bioprosthetic collagen porcine mesh during closure of the temporary ileostomy after laparoscopic TME for rectal cancer seems to decrease the chance of hernia formation at the stoma site, at least at the 1-year follow-up. PMID- 26260287 TI - Father's involvement and its effect on early breastfeeding practices in Viet Nam. AB - Fathers have an important but often neglected role in the promotion of healthy breastfeeding practices in developing countries. A community-based education intervention was designed to mobilize fathers' support for early breastfeeding. This study aimed to evaluate an education intervention targeting fathers to increase the proportion of early breastfeeding initiation and to reduce prelacteal feeding. Quasi-experimental study design was used to compare intervention and control areas located in two non-adjacent rural districts that shared similar demographic and health service characteristics in northern Viet Nam. Fathers and expectant fathers with pregnant wives from 7 to 30 weeks gestational age were recruited. Fathers in the intervention area received breastfeeding education materials, counselling services at a commune health centre and household visits. They were also invited to participate in a breastfeeding promotion social event. After intervention, early breastfeeding initiation rate was 81.2% in the intervention area and 39.6% in the control area (P < 0.001). Babies in the intervention area were more likely to be breastfed within the first hour after birth [odds ratio (OR) 7.64, 95% confidence interval (CI) 4.81-12.12] and not to receive any prelacteal feeding (OR 4.43, 95% CI 2.88 6.82) compared with those in the control area. Fathers may positively influence the breastfeeding practices of mothers, and as a resource for early childcare, they can be mobilized in programmes aimed at improving the early initiation of breastfeeding. PMID- 26260288 TI - STAT3 promotes CD1d-mediated lipid antigen presentation by regulating a critical gene in glycosphingolipid biosynthesis. AB - Cytokines that regulate the immune response signal through the Janus kinase / signal transducer and activation of transcription (JAK/STAT) pathway, but whether this pathway can regulate CD1d-mediated lipid antigen presentation to natural killer T (NKT) cells is unknown. Here, we found that STAT3 promotes antigen presentation by CD1d. Antigen-presenting cells (APCs) in which STAT3 expression was inhibited exhibited markedly reduced endogenous lipid antigen presentation to NKT cells without an impact on exogenous lipid antigen presentation by CD1d. Consistent with this observation, in APCs where STAT3 was knocked down, dramatically decreased levels of UDP glucose ceramide glucosyltransferase (UGCG), an enzyme involved in the first step of glycosphingolipid biosynthesis, were observed. Impaired lipid antigen presentation was reversed by ectopic expression of UGCG in STAT3-silenced CD1d(+) APCs. Hence, by controlling a fundamental step in CD1d-mediated lipid antigen presentation, STAT3 signalling promotes innate immune responses driven by CD1d. PMID- 26260290 TI - Simvastatin protects Sertoli cells against cisplatin cytotoxicity through enhanced gap junction intercellular communication. AB - Cisplatin, an important chemotherapeutic agent against testicular germ cell cancer, induces testicular toxicity on Leydig and Sertoli cells, leading to serious side-effects such as azoospermia and infertility. In a previous study, it was found that simvastatin enhanced the sensitivity of Leydig tumor cells to chemotherapeutic toxicity through the enhancement of gap junction functions. In the present study, the effect of simvastatin on the sensitivity of normal Sertoli cells to cisplatin and the role of gap junctions in such effects was investigated. The results showed that, simvastatin attenuated cisplatin toxicity only when cells exhibited high-density culture where gap junctional formation was possible. When gap junction function was decreased by the gap junction inhibitor or by siRNA targeting connexin 43, the protective effect of simvastatin to cisplatin toxicity was substantially attenuated. Simvastatin also enhanced gap junction functions between Sertoli cells. This effect was mediated by the reduction of PKC-mediated connexin phosphorylation, thereby increasing connexin 43 membrane localization. Thus, simvastatin-induced enhancement of gap junction mediated intercellular communication attenuated cisplatin toxicity on Sertoli cells. This result indicated that enhancement of gap junction function by simvastatin may have bilateral beneficial effects on cisplatin-based chemotherapy, enhancing cisplatin killing on cancer while ameliorating the reproduction toxicity. PMID- 26260289 TI - A critical role of Oct4A in mediating metastasis and disease-free survival in a mouse model of ovarian cancer. AB - BACKGROUND: High grade epithelial ovarian cancer (EOC) is commonly characterised by widespread peritoneal dissemination and ascites. Metastatic EOC tumour cells can attach directly to neighbouring organs or alternatively, maintain long term tumourigenicity and chemoresistance by forming cellular aggregates (spheroids). Cancer stem-like cells are proposed to facilitate this mechanism. This study aimed to investigate the role of Oct4A, an embryonic stem cell factor and known master regulator of pluripotency in EOC progression, metastasis and chemoresistance. METHODS: To investigate the expression of Oct4A in primary EOC tumours, IHC and qRT-PCR analyses were used. The expression of Oct4A in chemonaive and recurrent EOC patient ascites-derived tumour cells samples was investigated by qRT-PCR. The functional role of Oct4A in EOC was evaluated by generating stable knockdown Oct4A clones in the established EOC cell line HEY using shRNA-mediated silencing technology. Cellular proliferation, spheroid forming ability, migration and chemosensitivty following loss of Oct4A in HEY cells was measured by in vitro functional assays. These observations were further validated in an in vivo mouse model using intraperitoneal (IP) injection of established Oct4A KD clones into Balb/c nu/nu mice. RESULTS: We demonstrate that, compared to normal ovaries Oct4A expression significantly increases with tumour dedifferentiation. Oct4A expression was also significantly high in the ascites derived tumour cells of recurrent EOC patients compared to chemonaive patients. Silencing of Oct4A in HEY cells resulted in decreased cellular proliferation, migration, spheroid formation and increased chemosensitivity to cisplatin in vitro. IP injection of Oct4A knockdown cells in vivo produced significantly reduced tumour burden, tumour size and invasiveness in mice, which overall resulted in significantly increased mouse survival rates compared to mice injected with control cells. CONCLUSIONS: This data highlights a crucial role for Oct4A in the progression and metastasis of EOC. Targeting Oct4A may prove to be an effective strategy in the treatment and management of epithelial ovarian tumours. PMID- 26260292 TI - Spatial and temporal variation in the association between temperature and salmonellosis in NZ. AB - OBJECTIVE: Modelling the relationship between weather, climate and infectious diseases can help identify high-risk periods and provide understanding of the determinants of longer-term trends. We provide a detailed examination of the non linear and delayed association between temperature and salmonellosis in three New Zealand cities (Auckland, Wellington and Christchurch). METHODS: Salmonella notifications were geocoded to the city of residence for the reported case. City specific associations between weekly maximum temperature and the onset date for reported salmonella infections (1997-2007) were modelled using non-linear distributed lag models, while controlling for season and long-term trends. RESULTS: Relatively high temperatures were positively associated with infection risk in Auckland (n=3,073) and Christchurch (n=880), although the former showed evidence of a more immediate relationship with exposure to high temperatures. There was no significant association between temperature and salmonellosis risk in Wellington. CONCLUSIONS: Projected increases in temperature with climate change may have localised health impacts, suggesting that preventative measures will need to be region-specific. This evidence contributes to the increasing concern over the public health impacts of climate change. PMID- 26260291 TI - Inhibitory effects and actions of pentacyclic triterpenes upon glycation. AB - Pentacyclic triterpenic compounds including asiatic, betulinic, maslinic, oleanolic and ursolic acid occur naturally in many herbs and plant foods. It is well known that these triterpenoids possess anti-oxidative and anti-inflammatory activities. Furthermore, recent in vitro and in vivo researches indicated that these compounds could inhibit the production of advanced glycation end-products (AGEs). The impact of these triterpenes upon the activity and protein expression of enzymes involved in polyol pathway including aldose reductase and sorbitol dehydrogenase has been examined, and positive results are reported. These studies suggest that certain triterpenes are potent anti-glycative agents, and may benefit the prevention and/or therapy of glycation-related diseases such as diabetes mellitus and Alzheimer's disease. In this review article, the anti glycative activity and action mode of certain triterpenes are highlighted. These information may promote the anti-glycative application of these natural compounds. PMID- 26260293 TI - Twenty-year follow-up of newborn screening for patients with muscular dystrophy. AB - INTRODUCTION: An opt-out newborn screening (NBS) program for Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) was implemented at 2 hospitals in Pittsburgh, Pennsylvania, between 1987 and 1995. METHODS: For patients and their parents in families who received a diagnosis of DMD or BMD, either by NBS or by traditional diagnostics after symptom onset, attitudes toward NBS for DMD and BMD were assessed. RESULTS: All patients and most parents supported NBS for DMD and BMD. In contrast to the NBS parent cohort, the non-NBS cohort felt that diagnosis by NBS would cause anxiety. CONCLUSIONS: There was strong support of NBS for DMD and BMD in both patients and their parents in families who received a diagnosis through NBS or through traditional diagnostics. No negative psychosocial impacts of NBS were identified among those families who received a diagnosis through NBS. PMID- 26260294 TI - An EBV-based plasmid can replicate and maintain in stem cells. AB - Viral vectors have a wide range of applications in biology, particularly in gene therapy. Based on their integration capacity, viral vectors are classified as either integrating or non-integrating vectors. Although integrating vectors, such as lentivectors, have the ability to direct prolonged expression of exogenous genes, manipulation of the host genome is an inappropriate feature of these gene delivery tools. Non-integrating vectors, such as episomal replicating plasmids, can replicate and persist in host cells for long periods without any chromosomal interruption. These advantages made them good tools for gene induction purposes in gene therapy and basic studies. Due to the necessity of gene induction in stem cells for study of mammalian development and targeted differentiation, the use of integrating vectors for prolonged expression of genes of interest has been developed. Application of replicating plasmids can overcome some drawbacks associated with integrating vectors, although replication and maintenance of these plasmids can differ between cell types. Previously, it has been shown that such plasmids can be maintained in human embryonic stem cells for more than one month, but the rate of the plasmid replication during the host cell cycle has not been elucidated. In the present study, we showed that an EBV-based plasmid can replicate simultaneously with host in pluripotent and multipotent human and mouse stem cells and can be sustained for long time periods in dividing cells. PMID- 26260296 TI - Intravenous tryptophan administration attenuates cortisol secretion induced by intracerebroventricular injection of noradrenaline. AB - This study was conducted to investigate the possibility of suppression of stress induced cortisol (CORT) secretion by tryptophan (TRP) administration and to better understand its regulatory mechanisms by using a noradrenaline (NA) injection into the third ventricle (3V) as a stress model in cattle. A total of 25 Holstein steers with a cannula in the 3V were used. First, the increase in CORT secretion was observed following a NA injection into the 3V in a dose dependent manner, verifying the appropriateness of this treatment as a stress model of CORT secretion (Experiment 1). The effect of prior-administration of TRP into peripheral blood with a dose that has been demonstrated to increase brain 5 hydroxytryptamine levels on the elevation of plasma CORT induced by NA or corticotropin-releasing hormone (CRH) was then examined (Experiment 2). The prior administration of TRP suppressed NA-induced, but not CRH-induced, CORT elevation. These results suggest that an increase in TRP absorption into peripheral blood could suppress the stress-induced CORT secretion in cattle via the attenuation of the stimulatory effect of NA on the hypothalamic CRH release. PMID- 26260297 TI - Symptomatic Lymphocele Formation After Sentinel Lymph Node Biopsy for Early Stage Cervical Cancer. AB - In early stage cervical cancer, nodal status is the most important prognostic factor, and execution of retroperitoneal lymphadenectomy is currently an integral part of surgical therapy. Sentinel lymph node biopsy has been progressively incorporated with surgical therapy and could reduce morbidity. However, the current incidence of complications exclusively related to the procedure is unknown. We report on a 29-year-old woman affected by cervical cancer (Federation Internationale de Gynecologie et d'Obstetrique Stage 1b1), who underwent sentinel lymph node biopsy in combination with radical vaginal trachelectomy, and who later developed a symptomatic pelvic lymphocele that required surgical therapy. Conservative procedures in the pelvic lymph nodes are not free of complications, especially with regard to the formation of symptomatic lymphoceles. This report brings to light an important discussion about the exact magnitude of the complications associated with the procedure. PMID- 26260298 TI - Robotic Single-Site Endometriosis Resection Using Firefly Technology. AB - STUDY OBJECTIVE: To demonstrate the feasibility of robotic single-site resection of advanced endometriosis using new technology. DESIGN: We show a video that demonstrates our technique for accomplishing single-site laparoscopic resection of advanced endometriosis. The video is a step-by-step explanation of robotic single-site resection of endometriosis nodules overlying the ureter and rectum. BACKGROUND: Laparoscopic surgery has been shown to effectively improve pain and fertility in women with endometriosis [1]. Compared with traditional multiport laparoscopy, single-incision laparoscopy is associated with similar incidence rates of blood loss, conversion to open laparotomy, and wound complications, but it has superior cosmetic outcomes and high patient satisfaction [2-5]. Furthermore, robotic single-incision laparoscopy combined with robotic Firefly technology potentially increases the removal of invisible endometriosis. Without complete resection of endometriosis, patients are less likely to achieve full pain relief postoperatively. SETTING: University hospital. PATIENT: A 36 year old G1P1 female was referred for chronic pelvic pain. She described her pain as hip pain, pain with walking, dyspareunia, dyschezia and right anterior abdominal wall pain. INTERVENTION: To improve detection of endometriosis, we injected the patient with indocyanine green (ICG), a fluorescent dye with widespread medical applications in identifying increased vascularity of tissues. We then visualized the tissues with robotic Firefly technology, a fluorescence-detection tool built into the da Vinci SI Surgical Systems (Intuitive Surgical, Inc, Sunnyvale, CA). MAIN RESULTS: Because endometriosis lesions are associated with a high degree of neovascularization, the ICG turned the endometriosis tissues dark green, thereby enabling us to detect endometriosis that would not have been seen as readily with conventional single-site laparoscopy. This video demonstrates our technique for successfully accomplishing a single-site laparoscopic resection of advanced endometriosis, including ureterolysis, adhesiolysis, peritoneal stripping, and a rectal nodule excision. CONCLUSIONS: We found that Firefly technology and ICG facilitated identification of endometriosis in single-site robotic surgery. We were able to successfully perform single-site laparoscopic resection of advanced endometriosis nodules overlying the ureter and rectum with complete resolution of pelvic pain symptoms and excellent cosmetic results. PMID- 26260299 TI - Hysteroscopic Endometrial Resection Versus Laparoscopic Supracervical Hysterectomy for Abnormal Uterine Bleeding: Long-Term Follow-Up of a Randomized Trial. PMID- 26260300 TI - Providing Re-Essure-ance to the Nickel-Allergic Patient Considering Hysteroscopic Sterilization. AB - Essure is a popular method of permanent sterilization that offers a minimally invasive approach that avoids the risks of traditional sterilization procedures in the operating room. Despite the rarity of complications, there has been concern in the popular media over the safety of Essure. We describe the third reported case of systemic contact dermatitis due to the nickel component of the device, with a resolution of symptoms following surgical removal of the inserts. Despite these cases, we believe that extremely rare complications such as this should not dissuade patients from choosing this safe, effective method of sterilization. PMID- 26260301 TI - Hysteroscopic Essure Inserts for Permanent Contraception: Extended Follow-Up Results of a Phase III Multicenter International Study. PMID- 26260302 TI - Contained Morcellation for Laparoscopic Myomectomy Within a Specially Designed Bag. AB - A technique of contained morcellation of uterine myomas within a bag specially designed for 2-port morcellation during laparoscopic myomectomy is described. Ten patients underwent in-bag morcellation of myomas with a tissue isolation bag (MorSafe) between November 2014 and January 2015. The MorSafe tissue isolation bag is a retort-shaped bag made of medical-grade flexible plastic material with the wider opening of 134 mm in diameter and the tail end measuring 4 mm in diameter, allowing easy accomodation of specimens up to 12 cm in diameter. This technique involves placing the myomas into the isolation bag within the abdomen, exteriorizing the tail end of the bag, insufflating the bag within the peritoneal cavity, and morcellating the myomas under vision. Demographic and perioperative characteristics were studied. The mean operative time was 117 minutes (range, 75 195 minutes), the mean time for specimen introduction into the bag was 12.5 minutes (range, 7-22 minutes), and the mean time for morcellation and bag removal was 24.8 minutes (range, 10-50 minutes). There were no complications related to the in-bag morcellation technique, and there was no visual evidence of damage to the isolation bag. In-bag morcellation using this new bag is a feasible technique for morcellating uterine myomas in a contained manner and may provide an option to minimize the risks of open power morcellation while preserving the benefits of minimally invasive surgery. PMID- 26260303 TI - Hysteroscopic Myomectomy of FIGO Type 2 Leiomyomas Under Local Anesthesia: Bipolar Radiofrequency Needle-Based Release Followed By Electromechanical Morcellation. AB - OBJECTIVE: To demonstrate a technique designed to expand the capabilities of hysteroscopic intrauterine morcellators to deep type 1 and type 2 lesions. The technique comprises "release" of the tumor using a bipolar radiofrequency needle, followed by dissection and extraction with an electromechanical morcellator, all under local anesthesia. DESIGN: Description of technique using images and video (Canadian Task Force classification Class III). SETTING: Office uterine procedure and imaging center; academic medical center. INTERVENTION: Following the administration of local anesthesia and access to the endometrial cavity with a 5.5-mm-o.d. hysteroscopic sheath with a 5 Fr operative channel, a 5 Fr bipolar needle electrode system is used to circumscribe the leiomyoma and enter the pseudocapsule, thereby "releasing" the lesion. Blunt dissection is performed as appropriate and then the system is switched to a hysteroscopic morcellating system (MyoSure; Hologic, Bedford, MA), which is then used to further dissect and remove the target lesion with electromechanical morcellation. CONCLUSION: The development of intrauterine morcellators has facilitated the performance of hysteroscopic myomectomy, especially under local anesthesia, but the side aperture-based design of the systems limits their use in International Federation of Gynecology and Obstetrics (FIGO) type 1 and 2 tumors, particularly those located at the uterine fundus. This technique, based in part on a previously published technique of leiomyoma release, improves access of the electromechanical morcellator to leiomyomas that previously were inaccessible, and minimizes myometrial trauma by dissecting the tumor via the relatively avascular pseudocapsule. PMID- 26260304 TI - Laparoscopic and open right-sided colonic resection in daily routine practice. A prospective multicentre study within an Enhanced Recovery After Surgery (ERAS) protocol. AB - AIM: The study compared the outcome of laparoscopic and open surgery in daily practice when performed in a strict Enhanced Recovery After Surgery (ERAS) environment. METHOD: Two-hundred and ninety-two consecutive patients who received elective surgery, in three Swedish ERAS centres, for cancer or adenoma in the right colon in the period 1 January 2011 to 31 December 2012, were prospectively registered in a Web-based ERAS database. Peri-operative data were collected from the database and patient charts. The primary end-points included postoperative recovery and morbidity. The secondary objective was to identify preoperative variables that influenced the selection of patients for laparoscopic or open surgery. RESULTS: One-hundred and twenty-three (42%) patients were selected for laparoscopic surgery. The overall preoperative ERAS-compliance rate was 87% and no significant difference was seen between the surgical techniques. In multivariate analysis, patients treated with laparoscopy had significantly earlier pain control (2.4 +/- 3.2 days vs 4.2 +/- 5.9 days; P = 0.016) and a shorter length of hospital stay (LOS) (4 days vs 6 days; P = 0.002) compared with open surgery. There was no significant difference in the complication rate [18.7% vs 21.3%; OR = 1.0 (95% CI: 0.5-2.0)], the number of lymph nodes removed or the rate of R0 resection between laparoscopic and open surgery. Tumours selected for laparoscopy were generally smaller, had a lower T-stage and were predominantly situated in the caecum and the ascending colon compared with those of patients selected for open surgery. CONCLUSION: The use of laparoscopy in routine right sided colectomy in an ERAS environment, with data on outcome corrected for selection bias, may result in faster recovery compared with open surgery. PMID- 26260305 TI - Detecting patterns of species diversification in the presence of both rate shifts and mass extinctions. AB - BACKGROUND: Recent methodological advances allow better examination of speciation and extinction processes and patterns. A major open question is the origin of large discrepancies in species number between groups of the same age. Existing frameworks to model this diversity either focus on changes between lineages, neglecting global effects such as mass extinctions, or focus on changes over time which would affect all lineages. Yet it seems probable that both lineages differences and mass extinctions affect the same groups. RESULTS: Here we used simulations to test the performance of two widely used methods under complex scenarios of diversification. We report good performances, although with a tendency to over-predict events with increasing complexity of the scenario. CONCLUSION: Overall, we find that lineage shifts are better detected than mass extinctions. This work has significance to assess the methods currently used to estimate changes in diversification using phylogenetic trees. Our results also point toward the need to develop new models of diversification to expand our capabilities to analyse realistic and complex evolutionary scenarios. PMID- 26260306 TI - Phase II study of HCVIDD/MA in patients with newly diagnosed peripheral T-cell lymphoma. AB - A phase II study was performed to evaluate the efficacy of hyper-fractionated cyclophosphamide, vincristine, pegylated liposomal doxorubicin and dexamethasone alternating with methotrexate/cytarabine (HCVIDD/MA) in patients with newly diagnosed peripheral T-cell lymphoma (PTCL), excluding ALK-positive anaplastic large cell lymphoma. Fifty-three patients were enrolled. Treatment was planned for up to 8 cycles but only 9% of patients received more than 6 cycles due primarily to disease progression (n = 13) or prolonged thrombocytopenia (n = 12). The overall response rate was 66% with a complete response rate of 57%. Median progression-free survival (PFS) was 7.5 months. With a median follow-up of 7.6 years, 5-year PFS and overall survival (OS) were 21% and 48%, respectively. The patients with extranodal Natural Killer-cell lymphoma had a shorter PFS (median, 2.4 months) than other subtypes. Grade 3/4 anaemia, neutropenia and thrombocytopenia were observed in 66%, 74% and 79% of patients, respectively. Of note, 23% of patients discontinued therapy due to prolonged thrombocytopenia. In conclusion, HCVIDD/MA for the first-line treatment of PTCL patients is associated with significant myelosuppression leading to poor treatment adherence, and the response and survival outcomes with this regimen are similar to standard CHOP. This study was registered at www.clinicaltrials.gov as #NCT00290433. PMID- 26260308 TI - Use of Antihypertensive Drugs in Spain: National Trends From 2000 to 2012. PMID- 26260309 TI - Brief bursts of infrasound may improve cognitive function--an fMRI study. AB - At present, infrasound (sound frequency < 20 Hz; IS) is being controversially discussed as a potential mediator of several adverse bodily as well as psychological effects. However, it remains unclear, if and in what way IS influences cognition. Here, we conducted an fMRI experiment, in which 13 healthy participants were exposed to IS, while cognitive performance was assessed in an n back working memory paradigm. During the task, short sinusoidal tone bursts of 12 Hz were administered monaurally with sound pressure levels that had been determined individually in a categorical loudness scaling session prior to the fMRI experiment. We found that task execution was associated with a significant activation of the prefrontal and the parietal cortex, as well as the striatum and the cerebellum, indicating the recruitment of a cognitive control network. Reverse contrast analysis (n-back with tone vs. n-back without tone) revealed a significant activation of the bilateral primary auditory cortex (Brodmann areas 41, 42). Surprisingly, we also found a strong, yet non-significant trend for an improvement of task performance during IS exposure. There was no correlation between performance and brain activity measures in tone and no-tone condition with sum scores of depression-, anxiety-, and personality factor assessment scales (BDI, STAIX1/X2, BFI-S). Although exerting a pronounced effect on cortical brain activity, we obtained no evidence for an impairment of cognition due to brief bursts of IS. On the contrary, potential improvement of working memory function introduces an entirely new aspect to the debate on IS-related effects. PMID- 26260307 TI - Inflammation and plaque vulnerability. AB - Atherosclerosis is a maladaptive, nonresolving chronic inflammatory disease that occurs at sites of blood flow disturbance. The disease usually remains silent until a breakdown of integrity at the arterial surface triggers the formation of a thrombus. By occluding the lumen, the thrombus or emboli detaching from it elicits ischaemic symptoms that may be life-threatening. Two types of surface damage can cause atherothrombosis: plaque rupture and endothelial erosion. Plaque rupture is thought to be caused by loss of mechanical stability, often due to reduced tensile strength of the collagen cap surrounding the plaque. Therefore, plaques with reduced collagen content are thought to be more vulnerable than those with a thick collagen cap. Endothelial erosion, on the other hand, may occur after injurious insults to the endothelium instigated by metabolic disturbance or immune insults. This review discusses the molecular mechanisms involved in plaque vulnerability and the development of atherothrombosis. PMID- 26260310 TI - Medical liability, defensive medicine and professional insurance in otolaryngology. AB - BACKGROUND: This study aims at verifying relationships between the perception of medico-legal risks involved in the professional activity of Italian otolaryngologists, defensive medical behaviour and their understanding of professional liability insurance in matters of civil liability. One hundred specialists replied to a questionnaire pertaining to the psychological impact of medico-legal issues and to specific queries regarding insurance coverage, either privately stipulated or provided by the employer. Statistic analysis was carried out by chi(2) test and ANOVA multiple variance regression test, assuming P = 0.05 as the value of minimum statistical significance. RESULTS: It was found that in 50% of cases the behaviour of the doctor towards the patient had been decidedly influenced by concerns over medico-legal implications. In 29% of the sample these concerns had "often to always" influenced the choice of diagnostic procedures or treatment options, in order to safeguard themselves in case of legal dispute. The data obtained showed a statistically significant correlation between the level of concern (regarding potential medico-legal disputes) experienced by specialists on the one hand and variations in the doctor/patient relationship (P < 0.05) and the choice of defensive medical procedures (P < 0.05) on the other. Furthermore, the perception of the medico-legal problem was statistically related to the absence or poor knowledge of some insurance clauses, regarding posthumous coverage (72%), informed written consent (89%), and the coverage provided by the healthcare centre where the specialist is employed (32%) (P < 0.05). CONCLUSIONS: The results of this study indicate the necessity for a greater awareness of the actual guarantees provided by the insurance policy stipulated by specialists, to avoid inadequate coverage in the case of medico-legal disputes. PMID- 26260311 TI - Sensations of skin infestation linked to abnormal frontolimbic brain reactivity and differences in self-representation. AB - Some patients experience skin sensations of infestation and contamination that are elusive to proximate dermatological explanation. We undertook a functional magnetic resonance imaging study of the brain to demonstrate, for the first time, that central processing of infestation-relevant stimuli is altered in patients with such abnormal skin sensations. We show differences in neural activity within amygdala, insula, middle temporal lobe and frontal cortices. Patients also demonstrated altered measures of self-representation, with poorer sensitivity to internal bodily (interoceptive) signals and greater susceptibility to take on an illusion of body ownership: the rubber hand illusion. Together, these findings highlight a potential model for the maintenance of abnormal skin sensations, encompassing heightened threat processing within amygdala, increased salience of skin representations within insula and compromised prefrontal capacity for self regulation and appraisal. PMID- 26260313 TI - Assessment of the immune-modulatory and antimicrobial effects of dietary chitosan on Nile tilapia (Oreochrmis niloticus) with special emphasis to its bio remediating impacts. AB - Fish, pathogen and environment are three counterparts who are sharing the same circle of life. To keep fish up to their optimal health, environment should be competently improved and pathogen count/virulence should be seized. Using of bioactive immunostimulants to achieve these objectives is the hypothesis under assessment. Thus, the present study was performed to evaluate the use of shrimp shells derived chitosan as an immunostimulant as well as preventive regime against Aeromonas hydrophila infection of Nile tilapia and to assess its antibacterial/aquatic bio-remediating effects. Results achieved by feeding 1% chitosan as preventive/therapeutic regimes have revealed a remarkably enhanced several innate immunological parameters (e.g., Phagocytic activity/index, NBT, Lysozyme activity and ACH50), increased resistance against A. hydrophila and strikingly improved water quality compared to the 0.5 and 2% chitosan containing diets. Conclusively, experimental results suggest the commercial usage of chitosan as an efficient immunostimulant and bio-remediating agent in aquaculture. PMID- 26260312 TI - IGF-1 Regulates Vertebral Bone Aging Through Sex-Specific and Time-Dependent Mechanisms. AB - Advanced aging is associated with increased risk of bone fracture, especially within the vertebrae, which exhibit significant reductions in trabecular bone structure. Aging is also associated with a reduction in circulating levels of insulin-like growth factor (IGF-1). Studies have suggested that the reduction in IGF-1 compromises healthspan, whereas others report that loss of IGF-1 is beneficial because it increases healthspan and lifespan. To date, the effect of decreases in circulating IGF-1 on vertebral bone aging has not been thoroughly investigated. Here, we delineate the consequences of a loss of circulating IGF-1 on vertebral bone aging in male and female Igf(f/f) mice. IGF-1 was reduced at multiple specific time points during the mouse lifespan: early in postnatal development (crossing albumin-cyclic recombinase [Cre] mice with Igf(f/f) mice); and in early adulthood and in late adulthood using hepatic-specific viral vectors (AAV8-TBG-Cre). Vertebrae bone structure was analyzed at 27 months of age using micro-computed tomography (MUCT) and quantitative bone histomorphometry. Consistent with previous studies, both male and female mice exhibited age-related reductions in vertebral bone structure. In male mice, reduction of circulating IGF-1 induced at any age did not diminish vertebral bone loss. Interestingly, early-life loss of IGF-1 in females resulted in a 67% increase in vertebral bone volume fraction, as well as increased connectivity density and increased trabecular number. The maintenance of bone structure in the early-life IGF-1 deficient females was associated with increased osteoblast surface and an increased ratio of osteoprotegerin/receptor-activator of NF-kappaB-ligand (RANKL) levels in circulation. Within 3 months of a loss of IGF-1, there was a 2.2-fold increase in insulin receptor expression within the vertebral bones of our female mice, suggesting that local signaling may compensate for the loss of circulating IGF-1. Together, these data suggest the age-related loss of vertebral bone density in females can be reduced by modifying circulating IGF-1 levels early in life. PMID- 26260314 TI - Interferon regulatory factor 10 (IRF10): Cloning in orange spotted grouper, Epinephelus coioides, and evolutionary analysis in vertebrates. AB - IRF10 gene was cloned in orange spotted grouper, Epinephelus coioides, and its expression was examined following poly(I:C) stimulation and bacterial infection. The cDNA sequence of grouper IRF10 contains an open reading frame of 1197 bp, flanked by 99 bp 5'-untranslated region and 480 bp 3'- untranslated region. Multiple alignments showed that the grouper IRF10 has a highly conserved DNA binding domain in the N terminus with characteristic motif containing five tryptophan residues. Quantitative real-time PCR analysis revealed that the expression of IRF10 was responsive to both poly(I:C) stimulation and Vibrio parahemolyticus infection, with a higher increase to poly(I:C), indicating an important role of IRF10 in host immune response during infection. A phyletic distribution of IRF members was also examined in vertebrates, and IRF10 was found in most lineages of vertebrates, not in modern primates and rodents. It is suggested that the first divergence of IRF members might have occurred before the evolutionary split of vertebrate and cephalochordates, producing ancestors of IRF (1/2/11) and IRF (4/8/9/10)[(3/7) (5/6)], and that the second and/or third divergence of IRF members occurred following the split, thus leading to the subsets of the IRF family in vertebrates. PMID- 26260315 TI - Functions of MDA5 and its domains in response to GCRV or bacterial PAMPs. AB - Melanoma differentiation-associated gene 5 (MDA5) is a member of retinoic acid inducible gene I (RIG-I)-like receptor (RLR) family which can initiate type I IFN expression in response to RNA virus infection. In this study, we constructed six mutants of Ctenopharyngodon idella MDA5 (CiMAD5) overexpression plasmids and generated stable transfected C. idella kidney (CIK) cell lines to study the function of different domains of CiMAD5. After ploy(I:C) stimulation, the downstream genes of CiMDA5 in transfected cells was repressed. Overexpression of CiMDA5 or its variant repressed the replication of grass carp reovirus (GCRV) in CIK cells and decreased the viral titer of GCRV more or less compared to that in control cells. After GCRV or bacterial pathogen-associated molecular patterns (PAMPs) stimulation, overexpression of CiMDA5 or CARD domain significantly induced the expression of CiIFN-I, CiIL-1beta and CiMx1. The deletion of Helicase or RD domain reduced the inductive effect of CiMDA5 on CiIFN-I, CiIL-1beta and CiMx1 expression. RD overexpression resulted in an enhanced expression of CiIFN I, CiIL-1beta and CiMx1. These observations collectively demonstrate that, in CIK cells, after GCRV or bacterial PAMPs stimulation, CARD domain alone can mediate signaling; Helicase or RD domain alone negatively regulates CARD function by intramolecular interaction with CARD. However, RD domain acts as an enhancer by intermolecular interaction. These results enlarge the response spectrum of MDA5 and contribute to a further understanding of the functions of MDA5 and its domains in evolution. PMID- 26260316 TI - CgIkappaB3, the third novel inhibitor of NF-kappa B (IkappaB) protein, is involved in the immune defense of the Pacific oyster, Crassostrea gigas. AB - Inhibitor of NF-kappaB (IkappaB), the important regulator of NF-kappaB/Rel signaling pathway, plays the crucial role in immune response of both vertebrates and invertebrates. Here, a novel homologue of IkappaB was cloned from Crassostrea gigas, and designated as CgIkappaB3. The complete CgIkappaB3 cDNA was 1282 bp in length, including a 942 bp open reading frame (ORF), a 51 bp 5' UTR and a 289 bp 3' UTR. The ORF encodes a putative protein of 313 amino acids with a predicted molecular weight of approximately 34.7 kDa. Sequence analysis reveals that CgIkappaB3 contains a conserved degradation motif but with only five ankyrin repeats. Neither a PEST domain nor a C-terminal casein kinase II phosphorylation site was identified through either alignment or bioinformatic prediction. Phylogenetic analysis suggested that CgIkappaB3 shares common ancestor with CgIkappaB1 rather CgIkappaB2, and theoretically it may originate from one duplication event prior to divergence of CgIkappaB1 and CgIkappaB2. Tissue expression analyses demonstrated that CgIkappaB3 mRNA is the most abundant in gills and heart. The expression following PAMP infection showed that CgIkappaB3 was significantly up-regulated in a similar pattern when challenged with LPS, HKLM or HKVA, respectively. Moreover, similar to CgIkappaB1 and CgIkappaB2, CgIkappaB3 can also inhibit Rel dependent NF-kappaB activation in HEK293 cells in a dose-dependent manner. In summary, these findings suggest that CgIkappaB3 can be as the functional inhibitor of NF-kappaB/Rel and involved in the host defense of C. gigas. The discovery of the third IkappaB emphasizes the complexity and importance of the regulation on NF-kappaB activation. PMID- 26260317 TI - Does social desirability influence psychological well-being: perceived physical health and religiosity of Italian elders? A developmental approach. AB - OBJECTIVE: This study was mainly aimed at exploring the relationship between psychological well-being and lifestyle, religion, perceived physical health and social desirability of Italian elders. METHODS: Four hundred and six cognitively healthy 65-99 years old participants were recruited from the Italian isle of Sardinia, where a high prevalence of centenarians is registered. Participants were presented with several tools assessing psychological well-being, lifestyle, social desirability, religiosity and subjective physical health. RESULTS: A hierarchical regression analysis revealed that the social desirability measure is the best predictor of general subjective well-being, whereas further predictors are age, perceived physical health and gardening. A significant but moderate relationship was also found between psychological well-being, subjective physical health and religiosity, while controlling for social desirability. CONCLUSIONS: Social desirability seems to contaminate the self-rating of psychological well being in late adulthood. Moreover, from a developmental perspective, age-related factors, life style and perceived physical health are strictly related to and therefore influence the perception of life quality in the third and fourth age. PMID- 26260318 TI - The Kanker Nazorg Wijzer (Cancer Aftercare Guide) protocol: the systematic development of a web-based computer tailored intervention providing psychosocial and lifestyle support for cancer survivors. AB - BACKGROUND: After primary treatment, many cancer survivors experience psychosocial, physical, and lifestyle problems. To address these issues, we developed a web-based computer tailored intervention, the Kanker Nazorg Wijzer (Cancer Aftercare Guide), aimed at providing psychosocial and lifestyle support for cancer survivors. The purpose of this article is to describe the systematic development and the study design for evaluation of this theory and empirical based intervention. METHODS/DESIGN: For the development of the intervention, the steps of the Intervention Mapping protocol were followed. A needs assessment was performed consisting of a literature study, focus group interviews, and a survey study to get more insight into cancer survivors' health issues. This resulted in seven problem areas that were addressed in the intervention: cancer-related fatigue, return to work, anxiety and depression, social relationships and intimacy, physical activity, diet, and smoking. To address these problem areas, the principles of problem-solving therapy and cognitive behavioral therapy are used. At the start of the intervention, participants have to fill in a screening questionnaire. Based on their answers, participants receive tailored advice about which problem areas deserve their attention. Participants were recruited from November 2013 through June 2014 by hospital staff from 21 hospitals in the Netherlands. Patients were selected either during follow-up visits to the hospital or from reviews of the patients' files. The effectiveness of the intervention is being tested in a randomized controlled trial consisting of an intervention group (n = 231) and waiting list control group (n = 231) with a baseline measurement and follow-up measurements at 3, 6, and 12 months. DISCUSSION: Using the Intervention Mapping protocol resulted in a theory and evidence-based intervention providing tailored advice to cancer survivors on how to cope with psychosocial and lifestyle issues after primary treatment. TRIAL REGISTRATION: Dutch Trial Register NTR3375. PMID- 26260320 TI - Transgene integration into the human AAVS1 locus enhances myosin II-dependent contractile force by reducing expression of myosin binding subunit 85. AB - The adeno-associated virus site 1 (AAVS1) locus in the human genome is a strong candidate for gene therapy by insertion of an exogenous gene into the locus. The AAVS1 locus includes the coding region for myosin binding subunit 85 (MBS85). Although the function of MBS85 is not well understood, myosin II-dependent contractile force may be affected by altered expression of MBS85. The effect of altered expression of MBS85 on cellular contractile force should be examined prior to the application of gene therapy. In this study, we show that transgene integration into AAVS1 and consequent reduction of MBS85 expression changes myosin II-dependent cellular contractile force. We established a human fibroblast cell line with exogenous DNA knocked-in to AAVS1 (KI cells) using the CRISPR/Cas9 genome editing system. Western blotting analysis showed that KI cells had significantly reduced MBS85 expression. KI cells also showed greater cellular contractile force than control cells. The increased contractile force was associated with phosphorylation of the myosin II regulatory light chain (MRLC). Transfection of KI cells with an MBS85 expression plasmid restored cellular contractile force and phosphorylation of MRLC to the levels in control cells. These data suggest that transgene integration into the human AAVS1 locus induces an increase in cellular contractile force and thus should be considered as a gene therapy to effect changes in cellular contractile force. PMID- 26260319 TI - Identification of novel regulatory NFAT and TFII-I binding elements in the calbindin-D28k promoter in response to serum deprivation. AB - Calbindin-D28k, a key regulator of calcium homeostasis plays a cytoprotective role in various tissues. We used serum free (SFM) and charcoal stripped serum (csFBS) culture media as models of cellular stress to modulate calbindin D28k expression and identify regulatory cis-elements and trans-acting factors in kidney and beta cells. The murine calbindin-D28k promoter activity was significantly upregulated under SFM or csFBS condition. Promoter analysis revealed evolutionary conserved regulatory cis-elements and deletion of 23 nt from +117/+139 as critical for basal transcription. Bioinformatics analysis of the promoter revealed conserved NFAT and TFII regulators elements. Forced expression of NFAT stimulated promoter activity. Inhibition of NFAT transcriptional activity by FK506 attenuated calbindin-D28k expression. TFII-I was shown to be necessary for basal promoter activity and to act cooperatively with NFAT. Using chromatin immunoprecipitation (ChIP) assays, NFAT was shown to bind to both proximal and distal promoter regions. ChIP assays also revealed recruitment of TFII to the -36/+139 region. Knockdown of TFII-I decreased promoter activity. In summary, calbindin-D28k expression during serum deprivation is partly regulated by NFAT and TF-II. This regulation may be important in vivo during ischemia and growth factor withdrawal to regulate cellular function and maintenance. PMID- 26260321 TI - XEDAR activates the non-canonical NF-kappaB pathway. AB - Members of the tumor necrosis factor receptor (TNFR) superfamily are involved in a number of physiological and pathological responses by activating a wide variety of intracellular signaling pathways. The X-linked ectodermal dysplasia receptor (XEDAR; also known as EDA2R or TNFRSF27) is a member of the TNFR superfamily that is highly expressed in ectodermal derivatives during embryonic development and binds to ectodysplasin-A2 (EDA-A2), a member of the TNF family that is encoded by the anhidrotic ectodermal dysplasia (EDA) gene. Although XEDAR was first described in the year 2000, its function and molecular mechanism of action is still largely unclear. XEDAR has been reported to activate canonical nuclear factor kappaB (NF-kappaB) signaling and mitogen-activated protein (MAP) kinases. Here we report that XEDAR is also able to trigger the non-canonical NF-kappaB pathway, characterized by the processing of p100 (NF-kappaB2) into p52, followed by nuclear translocation of p52 and RelB. We provide evidence that XEDAR-induced p100 processing relies on the binding of XEDAR to TRAF3 and TRAF6, and requires the kinase activity of NIK and IKKalpha. We also show that XEDAR stimulation results in NIK accumulation and that p100 processing is negatively regulated by TRAF3, cIAP1 and A20. PMID- 26260322 TI - Mechano-regulation of gap junction communications between tendon cells is dependent on the magnitude of tensile strain. AB - Large magnitudes of mechanical strain applied to tendon cells induce catabolic and inflammatory responses, whereas a moderate level of strain promotes anabolism. Gap junction intercellular communication (GJIC) plays an essential role in these responses, however direct regulation of GJIC by mechanical loading has not been characterised in detail. Here, we show that the GJIC between tenocytes are enhanced or inhibited depending on the magnitude of the tensile strain. The GJIC was analysed using fluorescence loss in photobleaching (FLIP), combined with a molecular diffusion model. Intercellular and intracellular transport of fluorescence tracer molecules, calcein, across multiple cells through the gap junctions was evaluated by determining the intercellular and intracellular diffusion coefficients of calcein. It was demonstrated that the intercellular diffusion coefficient was significantly higher when the cells were subjected to a physiological static tensile strain (4%) for 1 h, but significantly lower when subjected to a strain with non-physiological amplitude (8%). The intracellular diffusion coefficient was not altered by the application of static strain at any level. Connexin 43 proteins were localised within cytoplasm and at cell-cell boundaries in no strained state and were also localised near cell nuclei by the 4% strain, but the localisation was reduced by the 8% strain. The findings suggest that the increase in GJIC in response to 4% strain involves opening of gap junction pores via mechanotransduction events of tenocytes, whereas the inhibition in response to 8% strain involves mechanical disruption of the junctions. PMID- 26260323 TI - Regulatory aspects on nanomedicines. AB - Nanomedicines have been in the forefront of pharmaceutical research in the last decades, creating new challenges for research community, industry, and regulators. There is a strong demand for the fast development of scientific and technological tools to address unmet medical needs, thus improving human health care and life quality. Tremendous advances in the biomaterials and nanotechnology fields have prompted their use as promising tools to overcome important drawbacks, mostly associated to the non-specific effects of conventional therapeutic approaches. However, the wide range of application of nanomedicines demands a profound knowledge and characterization of these complex products. Their properties need to be extensively understood to avoid unpredicted effects on patients, such as potential immune reactivity. Research policy and alliances have been bringing together scientists, regulators, industry, and, more frequently in recent years, patient representatives and patient advocacy institutions. In order to successfully enhance the development of new technologies, improved strategies for research-based corporate organizations, more integrated research tools dealing with appropriate translational requirements aiming at clinical development, and proactive regulatory policies are essential in the near future. This review focuses on the most important aspects currently recognized as key factors for the regulation of nanomedicines, discussing the efforts under development by industry and regulatory agencies to promote their translation into the market. Regulatory Science aspects driving a faster and safer development of nanomedicines will be a central issue for the next years. PMID- 26260324 TI - Barriers to universal health coverage in Republic of Moldova: a policy analysis of formal and informal out-of-pocket payments. AB - BACKGROUND: Universal Health Coverage seeks to assure that everyone can obtain the health services they need without financial hardship. Countries which rely heavily on out-of-pocket (OOP) payments, including informal payments (IP), to finance total health expenditures are not likely to achieve universal coverage. The Republic of Moldova is committed to promoting universal coverage, reducing inequities, and expanding financial protection. To achieve these goals, the country must reduce the proportion of total health expenditures paid by households. This study documents the extent of OOP payments and IP in Moldova, analyses trends over time, and identifies factors which may be driving these payments. METHODS: The study includes analysis of household budget survey data and previous research and policy documents. The team also conducted a review of administrative law intended to control OOP payments and IPs. Focus groups, interviews, and a policy dialogue with key stakeholders were held to validate and discuss findings. RESULTS: OOP payments account for 45% of total health expenditures. Sixteen percent of outpatients and 30% of inpatients reporting that they made OOP payments when seeking care at a health facility in 2012, more than two-thirds of whom also reported paying for medicines at a pharmacy. Among those who paid anything, 36% of outpatients and 82% of inpatients reported paying informally, with the proportion increasing over time for inpatient care. Although many patients consider these payments to be gifts, around one-third of IPs appear to be forced, posing a threat to health care access. Patients perceive that payments are driven by the limited list of reimbursable medicines, a desire to receive better treatment, and fear or extortion. Providers suggested irrational prescribing and ordering of tests as drivers. Providers may believe that IPs are gifts and do not cause harm for patients and the health system in general. CONCLUSIONS: Efforts to expand financial protection should focus on reducing household spending on medicines and hospital-based IPs. Reforms should consider ways to reduce medicine prices and promote rational use, strengthen administrative controls, and increase incentives for quality health care provision. PMID- 26260325 TI - A RCT of telehealth for COPD patient's quality of life: the whole system demonstrator evaluation. AB - INTRODUCTION/OBJECTIVES: Despite some concerns that the introduction of telehealth (TH) may lead to reductions in quality of life (QoL), lower mood and increased anxiety in response to using assistive technologies to reduce health care utilisation and manage long term conditions, this research focuses on the extent to which providing people with tools to monitor their condition can improve QoL. METHODS: The Chronic Obstructive Pulmonary Disease (COPD) cohort of the Whole Systems Demonstrator Trial is a pragmatic General Practitioner (GP) clustered randomised controlled trial (RCT) evaluating TH in the UK from three regions in England. All patients at a participating GP practice were deemed eligible for inclusion in the study if they were diagnosed with COPD. RESULTS: 447 participants completed baseline and either a short (4 months) or long term (12 months) follow-up. There was a trend of improved QoL and mood in the TH group at longer-term follow-up, but not short term follow-up. Emotional functioning (g = 0.280 95%CI, 0.051-0.510) and mastery reached (g = 2.979 95%CI, 0-0.46) significance at P < 0.05 (all Hedges g <0.3). CONCLUSIONS: TH showed minimal benefit to QoL in COPD patients who were not preselected to be at increased risk of acute exacerbations. Benefits were more likely in disease specific measures at longer term follow-up. TH is a complex intervention and should be embedded in a service that is evidenced based. Outcome measures must be sensitive enough to detect changes in the target population for the specific intervention. PMID- 26260326 TI - Cleaning of Oil Fouling with Water Enabled by Zwitterionic Polyelectrolyte Coatings: Overcoming the Imperative Challenge of Oil-Water Separation Membranes. AB - Herein we report a self-cleaning coating derived from zwitterionic poly(2 methacryloyloxylethyl phosphorylcholine) (PMPC) brushes grafted on a solid substrate. The PMPC surface not only exhibits complete oil repellency in a water wetted state (i.e., underwater superoleophobicity), but also allows effective cleaning of oil fouled on dry surfaces by water alone. The PMPC surface was compared with typical underwater superoleophobic surfaces realized with the aid of surface roughening by applying hydrophilic nanostructures and those realized by applying smooth hydrophilic polyelectrolyte multilayers. We show that underwater superoleophobicity of a surface is not sufficient to enable water to clean up oil fouling on a dry surface, because the latter circumstance demands the surface to be able to strongly bond water not only in its pristine state but also in an oil-wetted state. The PMPC surface is unique with its described self cleaning performance because the zwitterionic phosphorylcholine groups exhibit exceptional binding affinity to water even when they are already wetted by oil. Further, we show that applying this PMPC coating onto steel meshes produces oil water separation membranes that are resilient to oil contamination with simply water rinsing. Consequently, we provide an effective solution to the oil contamination issue on the oil-water separation membranes, which is an imperative challenge in this field. Thanks to the self-cleaning effect of the PMPC surface, PMPC-coated steel meshes can not only separate oil from oil-water mixtures in a water-wetted state, but also can lift oil out from oil-water mixtures even in a dry state, which is a very promising technology for practical oil-spill remediation. In contrast, we show that oil contamination on conventional hydrophilic oil-water separation membranes would permanently induce the loss of oil-water separation function, and thus they have to be always used in a completely water-wetted state, which significantly restricts their application in practice. PMID- 26260327 TI - Higher Prevalence of TDP-43 Proteinopathy in Cognitively Normal Asians: A Clinicopathological Study on a Multiethnic Sample. AB - Transactive response DNA binding protein 43 (TDP-43) proteinopathy is the major hallmark of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. It is also present in a subset of Alzheimer's disease cases. Recently, few reports showed TDP-43 changes in cognitively normal elderly. In Caucasians, TDP 43 proteinopathy independently correlate with cognitive decline. However, it is challenging to establish direct links between cognitive and/or neuropsychiatric symptoms and protein inclusions in neurodegenerative diseases because individual cognitive reserves modify the threshold for clinical disease expression. Cognitive reserve is influenced by demographic, environmental and genetic factors. We investigated the relationships between demographic, clinical and neuropathological variables and TDP-43 proteinopathy in a large multiethnic sample of cognitively normal elderly. TDP-43 proteinopathy was identified in 10.5%, independently associated with older age (P = 0.03) and Asian ethnicity (P = 0.002). Asians showed a higher prevalence of TDP-43 proteinopathy than Caucasians, even after adjustment for sex, age, Braak stage and schooling (odds ratio = 3.50, confidence interval 1.41-8.69, P = 0.007). These findings suggested that Asian older adults may be protected from the clinical manifestation of brain TDP-43 proteinopathy. Future studies are needed to identify possible race-related protective factors against clinical expression of TDP-43 proteinopathies. PMID- 26260328 TI - Strategies and new developments to control pertussis, an actual health problem. AB - The aim of this article is to describe the current epidemiological situation of pertussis, as well as different short-term strategies that have been implemented to alleviate this threat. The state of the art of the development of new vaccines that are expected to provide long-lasting immunity against pertussis was also included. PMID- 26260329 TI - A time-course study of long term over-expression of ARR19 in mice. AB - A leucine-rich protein, ARR19 (androgen receptor corepressor-19 kDa), is highly expressed in male reproductive organs and moderately in others. Previously, we have reported that ARR19 is differentially expressed in adult Leydig cells during the testis development and inhibits steroidogenesis by reducing the expression of steroidogenic enzymes. Whereas in prostate, ARR19 represses the transcriptional activity of AR (androgen receptor), it is important for male sexual differentiation and maturation in prostate and epididymis, through the recruitment of HDAC4. In this study we show that long term adenovirus mediated overexpression of ARR19 in mice testis has the potential of inhibiting the differentiation of testicular and prostatic cells by reducing the size of testis and prostate but has no effect on the growth of seminal vesicles. Further, it reduces the level of progesterone and testosterone by reducing the steroidogenic enzymes such as 3HSD, P450c17 and StAR. This is the first study reporting a time course analysis of the implications of long term overexpression of ARR19 in mice testis and its effect on other organs such as prostate and seminal vesicles. Taken together, these results suggest that ARR19 may play an important role in the differentiation of male reproductive organs such as testis and prostate. PMID- 26260330 TI - Global Metabonomic and Proteomic Analysis of Human Conjunctival Epithelial Cells (IOBA-NHC) in Response to Hyperosmotic Stress. AB - "Dry eye" is a multifactorial inflammatory disease affecting the ocular surface. Tear hyperosmolarity in dry eye contributes to inflammation and cell damage. Recent research efforts on dry eye have been directed toward biomarker discovery for diagnosis, response to treatment, and disease mechanisms. This study employed a spontaneously immortalized normal human conjunctival cell line, IOBA-NHC, as a model to investigate hyperosmotic stress-induced changes of metabolites and proteins. Global and targeted metabonomic analyses as well as proteomic analysis were performed on IOBA-NHC cells incubated in serum-free media at 280 (control), 380, and 480 mOsm for 24 h. Twenty-one metabolites and seventy-six iTRAQ identified proteins showed significant changes under at least one hyperosmotic stress treatment as compared with controls. SWATH-based proteomic analysis further confirmed the involvement of inflammatory pathways such as prostaglandin 2 synthesis in IOBA-NHC cells under hyperosmotic stress. This study is the first to identify glycerophosphocholine synthesis and O-linked beta-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. These findings extend the current knowledge in metabolite markers of dry eye and provide potential therapeutic targets for its treatment. PMID- 26260331 TI - HBsAg sT123N mutation induces stronger antibody responses to HBsAg and HBcAg and accelerates in vivo HBsAg clearance. AB - Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. Some mutants harboring substitutions to Asn in HBsAg MHR may have an additional potential N-glycosylation site. We have previously showed that sT123N substitution could generate additional N-glycosylated forms of HBsAg. In the present study, 1.3-fold-overlength HBV genomes containing the sT123N substitution were digested from the pHBV1.3-sT123N construct and subcloned into the pAAV vector to generate pAAV1.3-sT123N for hydrodynamic injection (HI) in mice. Viral expression and replication were phenotypically characterized by transient transfection. The results demonstrated that sT123N substitution impaired virion secretion, resulting in intracellular retention of HBcAg. Using the HBV HI mouse model, we found that mice mounted significantly stronger antibody responses to HBsAg and HBcAg, which accelerated HBsAg clearance. Thus, additional N glycosylation generated by amino acid substitutions in HBsAg MHR may significantly modulate specific host immune responses and influence HBV infection in vivo. Our results help further the understanding of the role of immune escape mutants with N-linked glycosylation in the biology of HBV infection. PMID- 26260332 TI - Enterovirus strain and type-specific differences in growth kinetics and virus induced cell destruction in human pancreatic duct epithelial HPDE cells. AB - Enterovirus infections have been suspected to be involved in the development of type 1 diabetes. However, the pathogenetic mechanism of enterovirus-induced type 1 diabetes is not known. Pancreatic ductal cells are closely associated with pancreatic islets. Therefore, enterovirus infections in ductal cells may also affect beta-cells and be involved in the induction of type 1 diabetes. The aim of this study was to assess the ability of different enterovirus strains to infect, replicate and produce cytopathic effect in human pancreatic ductal cells. Furthermore, the viral factors that affect these capabilities were studied. The pancreatic ductal cells were highly susceptible to enterovirus infections. Both viral growth and cytolysis were detected for several enterovirus serotypes. However, the viral growth and capability to induce cytopathic effect (cpe) did not correlate completely. Some of the virus strains replicated in ductal cells without apparent cpe. Furthermore, there were strain-specific differences in the growth kinetics and the ability to cause cpe within some serotypes. Viral adaptation experiments were carried out to study the potential genetic determinants behind these phenotypic differences. The blind-passage of non-lytic CV-B6-Schmitt strain in HPDE-cells resulted in lytic phenotype and increased progeny production. This was associated with the substitution of a single amino acid (K257E) in the virus capsid protein VP1 and the viral ability to use decay accelerating factor (DAF) as a receptor. This study demonstrates considerable plasticity in the cell tropism, receptor usage and cytolytic properties of enteroviruses and underlines the strong effect of single or few amino acid substitutions in cell tropism and lytic capabilities of a given enterovirus. Since ductal cells are anatomically close to pancreatic islets, the capability of enteroviruses to infect and destroy pancreatic ductal cells may also implicate in respect to enterovirus induced type 1 diabetes. In addition, the capability for rapid adaptation to different cell types suggests that, on occasion, enterovirus strains with different pathogenetic properties may arise from less pathogenic ancestors. PMID- 26260333 TI - Identification and complete genome analysis of a novel bovine picornavirus in Japan. AB - We identified novel viruses in feces from cattle with diarrhea collected in 2009 in Hokkaido Prefecture, Japan, by using a metagenomics approach and determined the (near) complete sequences of the virus. Sequence analyses revealed that they had a standard picornavirus genome organization, i.e. 5' untranslated region (UTR) - L- P1 (VP4- VP3- VP2- VP1) - P2 (2A- 2B- 2C) - P3 (3A- 3B- 3C-3D) - 3'UTR poly(A). They are closely related to other unclassified Chinese picornaviruses; bat picornaviruses group 1-3, feline picornavirus, and canine picornavirus, sharing 45.4-51.4% (P1), 38.0-44.9% (P2), and 49.6-53.3% (P3) amino acid identities, respectively. The phylogenetic analyses and detailed genome characterization showed that they, together with the unclassified Chinese picornaviruses, grouped as a cluster for the P1, 2C, 3CD and VP1 coding regions. These viruses had conserved features (e.g. predicted protein cleavage sites, presence of a leader protein, 2A, 2C, 3C, and 3D functional domains), suggesting they have a common ancestor. Reverse-transcription-PCR assays, using specific primers designed from the 5'UTR sequence of these viruses, showed that 23.0% (20/87) of fecal samples from cattle with diarrhea were positive, indicating the prevalence of these picornavirus in the Japanese cattle population in Hokkaido Prefecture. However, further studies are needed to investigate the pathogenic potential and etiological role of these viruses in cattle. PMID- 26260334 TI - Galantamine derivatives with indole moiety: Docking, design, synthesis and acetylcholinesterase inhibitory activity. AB - The inhibitors of acetylcholinesterase are the main therapy against Alzheimer's disease. Among them, galantamine is the best tolerated and the most prescribed drug. In the present study, 41 galantamine derivatives with known acetylcholinesterase inhibitory activities expressed as IC50 were selected from the literature and docked into a recombinant human acetylcholinesterase by GOLD. A linear relationship between GoldScores and pIC50 values was found and used to design and predict novel galantamine derivatives with indole moiety in the side chain. The four best predicted compounds were synthesized and tested for inhibitory activity. All of them were between 11 and 95 times more active than galantamine. The novel galantamine derivatives with indole moiety have dual site binding to the enzyme--the galantamine moiety binds to the catalytic anionic site and the indole moiety binds to peripheral anionic site. Additionally, the indole moiety of one of the novel inhibitors binds in a region, close to the peripheral anionic site of the enzyme, where the Omega-loop of amyloid beta peptide adheres to acetylcholinesterase. This compound emerges as a promising lead compound for multi-target anti-Alzheimer therapy not only because of the strong inhibitory activity, but also because it is able to block the amyloid beta deposition on acetylcholinesterase. PMID- 26260336 TI - 2- and 3-Fluoro-3-deazaneplanocins, 2-fluoro-3-deazaaristeromycins, and 3-methyl 3-deazaneplanocin: Synthesis and antiviral properties. AB - The 3-deaza analogs of the naturally occurring adenine-based carbocyclic nucleosides aristeromycin and neplanocin possess biological properties that have not been optimized. In that direction, this paper reports the strategic placement of a fluorine atom at the C-2 and C-3 positions and a methyl at the C-3 site of the 3-deazaadenine ring of the aforementioned compounds. The synthesis and S adenosylhomocysteine hydrolase inhibitory and antiviral properties of these targets are described. Some, but not all, compounds in this series showed significant activity toward herpes, arena, bunya, flavi, and orthomyxoviruses. PMID- 26260335 TI - Tight binding enantiomers of pre-clinical drug candidates. AB - MTDIA is a picomolar transition state analogue inhibitor of human methylthioadenosine phosphorylase and a femtomolar inhibitor of Escherichia coli methylthioadenosine nucleosidase. MTDIA has proven to be a non-toxic, orally available pre-clinical drug candidate with remarkable anti-tumour activity against a variety of human cancers in mouse xenografts. The structurally similar compound MTDIH is a potent inhibitor of human and malarial purine nucleoside phosphorylase (PNP) as well as the newly discovered enzyme, methylthioinosine phosphorylase, isolated from Pseudomonas aeruginosa. Since the enantiomers of some pharmaceuticals have revealed surprising biological activities, the enantiomers of MTDIH and MTDIA, compounds 1 and 2, respectively, were prepared and their enzyme binding properties studied. Despite binding less tightly to their target enzymes than their enantiomers compounds 1 and 2 are nanomolar inhibitors. PMID- 26260337 TI - Sulfation modulates the cell uptake, antiradical activity and biological effects of flavonoids in vitro: An examination of quercetin, isoquercitrin and taxifolin. AB - Quercetin 3'-O-sulfate is one of the main metabolites of the natural flavonoid quercetin in humans. This study was designed to prepare quercetin 3'-O-sulfate (1), isoquercitrin 4'-O-sulfate (2) and taxifolin 4'-O-sulfate (3) by the sulfation of quercetin, isoquercitrin (quercetin 3-O-glucoside) and taxifolin (2,3-dihydroquercetin) using the arylsulfate sulfotransferase from Desulfitobacterium hafniense, and to examine the effect of sulfation on selected biological properties of the flavonoids tested. We found that flavonoid sulfates 1-3 were weaker DPPH radical scavengers than the corresponding nonsulfated flavonoids, and that 1-3, unlike quercetin, did not induce the expression of either heme oxygenase-1 in RAW264.7 cells or cytochrome P450 1A1 in HepG2 cells. In both cell types, the cell uptake of compounds 1-3 was much lower than that of quercetin, but comparable to that of the glycoside isoquercitrin. Moreover, HPLC/MS metabolic profiling in HepG2 cells showed that flavonoid sulfates 1-3 were metabolized to a limited extent compared to the nonsulfated compounds. We conclude that sulfation of the tested flavonoids reduces their antiradical activity, and affects their cell uptake and biological activity in vitro. PMID- 26260338 TI - Novel metal chelating molecules with anticancer activity. Striking effect of the imidazole substitution of the histidine-pyridine-histidine system. AB - Previously we have reported a metal chelating histidine-pyridine-histidine system possessing a trityl group on the histidine imidazole, namely HPH-2Trt, which induces apoptosis in human pancreatic adenocarcinoma AsPC-1 cells. Herein the influence of the imidazole substitution of HPH-2Trt was examined. Five related compounds, HPH-1Trt, HPH-2Bzl, HPH-1Bzl, HPH-2Me, and HPH-1Me were newly synthesized and screened for their activity against AsPC-1 and brain tumor cells U87 and U251. HPH-1Trt and HPH-2Trt were highly active among the tested HPH compounds. In vitro DNA cleavage assay showed both HPH-1Trt and HPH-2Trt completely disintegrate pUC19 DNA. The introduction of trityl group decisively potentiated the activity. PMID- 26260339 TI - Highly potent artemisinin-derived dimers and trimers: Synthesis and evaluation of their antimalarial, antileukemia and antiviral activities. AB - New pharmaceutically active compounds can be obtained by modification of existing drugs to access more effective agents in the wake of drug resistance amongst others. To achieve this goal the concept of hybridization was established during the last decade. We employed this concept by coupling two artemisinin-derived precursors to obtain dimers or trimers with increased in vitro activity against Plasmodiumfalciparum 3D7 strain, leukemia cells (CCRF-CEM and multidrug-resistant subline CEM/ADR5000) and human cytomegalovirus (HCMV). Dimer 4 (IC50 of 2.6 nM) possess superior antimalarial activity compared with its parent compound artesunic acid(3) (IC50 of 9.0 nM). Dimer5 and trimers6 and 7 display superior potency against both leukemia cell lines (IC50 up to 0.002 MUM for CCRF-CEM and IC50 up to 0.20 MUM for CEM/ADR5000) and are even more active than clinically used doxorubicin (IC50 1.61 MUM for CEM/ADR5000). With respect to anti-HCMV activity, trimer6 is the most efficient hybrid (IC50 0.04 MUM) outperforming ganciclovir (IC50 2.6 MUM), dihydroartemisinin(IC50 >10 MUM) and artesunic acid (IC50 3.8 MUM). PMID- 26260340 TI - Synthesis, binding, nuclease resistance and cellular uptake properties of 2'-O acetalester-modified oligonucleotides containing cationic groups. AB - We report on the synthesis and properties of oligonucleotides (ONs) with 2'-O acetalester modifications containing cationic side chains in a prodrug-like approach. In the aim to improve cell penetration and nuclease resistance, various different amino- or guanidino-acetalester were grafted to 2'-OH of uridine and the corresponding phosphoramidites were incorporated into ONs. Introduction of 2' O-(2-aminomethyl-2-ethyl)butyryloxymethyl (AMEBuOM) modification into 2'-OMe ONs leads to high resistance towards enzymatic degradation and to destabilization of duplexes with complementary RNA strand. Spontaneous uptake experiments of a twelve-mer containing ten 2'-O-AMEBuOM-U units into A673 cells showed moderate internalization of ON within the cells whereas substantial internalization of the corresponding lipophilic 2'-O-pivaloyloxymethyl ON was observed for the first time. PMID- 26260341 TI - Carbon nanotubes supported tyrosinase in the synthesis of lipophilic hydroxytyrosol and dihydrocaffeoyl catechols with antiviral activity against DNA and RNA viruses. AB - Hydroxytyrosol and dihydrocaffeoyl catechols with lipophilic properties have been synthesized in high yield using tyrosinase immobilized on multi-walled carbon nanotubes by the Layer-by-Layer technique. All synthesized catechols were evaluated against a large panel of DNA and RNA viruses, including Poliovirus type 1, Echovirus type 9, Herpes simplex virus type 1 (HSV-1), Herpes simplex virus type 2 (HSV-2), Coxsackievirus type B3 (Cox B3), Adenovirus type 2 and type 5 and Cytomegalovirus (CMV). A significant antiviral activity was observed in the inhibition of HSV-1, HSV-2, Cox B3 and CMV. The mechanism of action of the most active dihydrocaffeoyl derivative was investigated against a model of HSV-1 infection. PMID- 26260342 TI - The gold/ampicillin interface at the atomic scale. AB - In the fight against antibiotic resistance, gold nanoparticles (AuNP) with antibiotics grafted on their surfaces have been found to be potent agents. Ampicillin-conjugated AuNPs have been thus reported to overcome highly ampicillin resistant bacteria. However, the structure at the atomic scale of these hybrid systems remains misunderstood. In this paper, the structure of the interface between an ampicillin molecule AMP and three flat gold facets Au(111), Au(110) and Au(100) has been investigated with numerical simulations (dispersion corrected DFT). Adsorption energies, bond distances and electron densities indicate that the adsorption of AMP on these facets goes through multiple partially covalent bonding. The stability of the AuNP/AMP nanoconjugates is explained by large adsorption energies and their potential antibacterial activity is discussed on the basis of the constrained spatial orientation of the grafted antibiotic. PMID- 26260343 TI - Function and diversity of P0 proteins among cotton leafroll dwarf virus isolates. AB - BACKGROUND: The RNA silencing pathway is an important anti-viral defense mechanism in plants. As a counter defense, some members of the viral family Luteoviridae are able to evade host immunity by encoding the P0 RNA silencing suppressor protein. Here we explored the functional diversity of P0 proteins among eight cotton leafroll dwarf virus (CLRDV) isolates, a virus associated with a worldwide cotton disease known as cotton blue disease (CBD). METHODS: CLRDV infected cotton plants of different varieties were collected from five growing fields in Brazil and their P0 sequences compared to three previously obtained isolates. P0's silencing suppression activities were scored based on transient expression experiments in Nicotiana benthamiana leaves. RESULTS: High sequence diversity was observed among CLRDV P0 proteins, indicating that some isolates found in cotton varieties formerly resistant to CLRDV should be regarded as new genotypes within the species. All tested proteins were able to suppress local and systemic silencing, but with significantly variable degrees. All P0 proteins were able to mediate the decay of ARGONAUTE proteins, a key component of the RNA silencing machinery. CONCLUSIONS: The sequence diversity observed in CLRDV P0s is also reflected in their silencing suppression capabilities. However, the strength of local and systemic silencing suppression was not correlated for some proteins. PMID- 26260344 TI - Therapeutic potential of antiviral drugs targeting chemorefractory colorectal adenocarcinoma cells overexpressing endogenous retroviral elements. AB - BACKGROUND: Endoretroviruses account for circa 8 % of all transposable elements found in the genome of humans and other animals. They represent a genetic footprint of ancestral germ-cell infections of exoviruses that is transmittable to the progeny by Mendelian segregation. Traces of human endogenous retroviruses are physiologically expressed in ovarial, testicular and placental tissues as well as in stem cells. In addition, a number of these fossil viral elements have also been related to carcinogenesis. However, a relation between endoretroviruses expression and chemoresistance has not been reported yet. METHODS: Twenty colorectal carcinoma patient samples were scrutinized for HERV-WE1 and HERV-FRD1 endoretroviruses using immunohistochemical approaches. In order to search for differential expression of these elements in chemotherapy refractory cells, a resistant HCT8 colon carcinoma subline was developed by serial etoposide exposure. Endoretroviral elements were detected by immunocytochemical staining, qPCR and ELISA. IC50-values of antiviral and cytostatic drugs in HCT8 cells were determined by MTT proliferation assay. The antivirals-cytostatics interaction was evaluated by the isobologram method. RESULTS: In this work, we show for the first time that HERV-WE1, HERV-FRD1, HERV-31, and HERV-V1 are a) simultaneously expressed in treatment-naive colon carcinoma cells and b) upregulated after cytostatic exposure, suggesting that these retroviral elements are intimately related to chemotherapy resistance. We found a number of antiviral drugs to have cytotoxic activity and the ability to force the downregulation of HERV proteins in vitro. We also demonstrate that the use of different antiviral compounds alone or in combination with anticancer agents results in a synergistic antiproliferative effect and downregulation of different endoretroviral elements in highly chemotherapy-resistant colorectal tumor cells. CONCLUSIONS: Enhanced HERV-expression is associated with chemoresistance in colon carcinomas which can be overcome by antiviral drugs alone or in combination with anticancer drugs. Therefore, the introduction of antiviral compounds to the current chemotherapy regimens potentially improves patient outcomes. PMID- 26260345 TI - Current pain education within undergraduate medical studies across Europe: Advancing the Provision of Pain Education and Learning (APPEAL) study. AB - OBJECTIVES: Unrelieved pain is a substantial public health concern necessitating improvements in medical education. The Advancing the Provision of Pain Education and Learning (APPEAL) study aimed to determine current levels and methods of undergraduate pain medicine education in Europe. DESIGN AND METHODS: Using a cross-sectional design, publicly available curriculum information was sought from all medical schools in 15 representative European countries in 2012-2013. Descriptive analyses were performed on: the provision of pain teaching in dedicated pain modules, other modules or within the broader curriculum; whether pain teaching was compulsory or elective; the number of hours/credits spent teaching pain; pain topics; and teaching and assessment methods. RESULTS: Curriculum elements were publicly available from 242 of 249 identified schools (97%). In 55% (133/242) of schools, pain was taught only within compulsory non pain-specific modules. The next most common approaches were for pain teaching to be provided wholly or in part via a dedicated pain module (74/242; 31%) or via a vertical or integrated approach to teaching through the broader curriculum, rather than within any specific module (17/242; 7%). The curricula of 17/242 schools (7%) showed no evidence of any pain teaching. Dedicated pain modules were most common in France (27/31 schools; 87%). Excluding France, only 22% (47/211 schools) provided a dedicated pain module and in only 9% (18/211) was this compulsory. Overall, the median number of hours spent teaching pain was 12.0 (range 4-56.0 h; IQR: 12.0) for compulsory dedicated pain modules and 9.0 (range 1.0-60.0 h; IQR: 10.5) for other compulsory (non-pain specific) modules. Pain medicine was principally taught in classrooms and assessed by conventional examinations. There was substantial international variation throughout. CONCLUSIONS: Documented pain teaching in many European medical schools falls far short of what might be expected given the prevalence and public health burden of pain. PMID- 26260346 TI - Temporal trends in cardiovascular disease risk factors among white, South Asian, Chinese and black groups in Ontario, Canada, 2001 to 2012: a population-based study. AB - OBJECTIVES: To determine ethnic-specific temporal trends in cardiovascular risk factors in Ontario between 2001 and 2012. DESIGN: A population-based repeated cross-sectional study. SETTING: Ontario, Canada. PARTICIPANTS: 219,276 participants of the Canadian Community Health Survey (205,326 white, 5620 South Asian, 4368 Chinese and 3962 black) during the period 2001 to 2012. MAIN OUTCOME MEASURES: Age-standardised ethnic-sex-specific prevalence of cardiovascular risk factors for three time periods: 2001-2004, 2005-2008 and 2009-2012 among Canada's four major ethnic groups: white, South Asian, Chinese and black. RESULTS: During the study period, the prevalence of diabetes increased 2.3-fold (p = 0.0001) among South Asian males and 1.9-fold (p = 0.02) among black females. The prevalence of obesity (body mass index >= 30 kg/m(2)) increased over time across all ethnic groups, with the largest relative increases observed among males of Chinese (2.1-fold increase, p = 0.04) and black (1.7-fold increase, p = 0.06) descent. The prevalence of hypertension increased the most among black females. Smoking prevalence decreased by more than 20% among South Asian, Chinese and white females. Overall, South Asian males and black males and females showed the greatest declines in cardiovascular health over the study period. CONCLUSIONS: We observed important ethnic differences in the temporal trends in cardiovascular risk factor profiles in Ontario. Awareness of the direction and magnitude of these risk factor trends may be useful in informing targeted strategies for preventing cardiovascular diseases in multiethnic populations. PMID- 26260347 TI - Identification and prevalence of adverse drug events caused by potentially inappropriate medication in homebound elderly patients: a retrospective study using a nationwide survey in Japan. AB - OBJECTIVES: A nationwide large-scale survey was conducted to identify the prevalence and causal medications of adverse drug events (ADEs) that are caused by potentially inappropriate medications (PIMs) given to homebound elderly patients, factors associated with ADEs, and measures taken by pharmacists to manage ADEs and their effects on ADEs. SETTINGS: A questionnaire was mailed to 3321 pharmacies nationwide. It asked about the details of PIMs and ADEs of up to 5 patients for whom home visits were provided by a pharmacist. Questionnaire forms were filled in by pharmacists who visited the patients. DESIGN AND PARTICIPANTS: Between 23 January and 13 February 2013, comprehensive assessment forms were sent to 3321 pharmacies. Data collected from 1890 pharmacies including data of 4815 patients were analysed and 28 patients of unknown sex were excluded. Their average age was 82.7 years. PIMs were identified based on the 2003 Beers Criteria Japan. RESULTS: There were 600 patients who did not provide valid answers regarding the medications. In the remaining 4243 patients, one or more medications that were considered to be PIMs had been prescribed to 48.4% of patients. PIM-induced ADEs were found in 8% of these patients by pharmacists during home visits. The top ADE-inducing medications were strong anticholinergic antihistamines, benzodiazepines, sulpiride and digoxin. The most common ADEs associated with benzodiazepines were frequent lightheadedness, somnolence and sleepiness, which increase the risk of falls and subsequent fractures in elderly patients. The following factors associated with ADEs were identified: sex, pharmacist awareness of prescription issues, frequency of visits and time spent at patients' homes, and the frequency of detailed checks for patient adverse reactions by pharmacists. CONCLUSIONS: The PIM prevalence associated with home healthcare in Japan was relatively high, as reported in previous studies. The present study suggests that pharmacists could reduce the incidence of PIMs and consequent ADEs. PMID- 26260348 TI - Behavioural physical activity interventions in participants with lower-limb osteoarthritis: a systematic review with meta-analysis. AB - OBJECTIVE: To assess effectiveness of osteoarthritis interventions to promote long-term physical activity behaviour change. DESIGN: A systematic review and meta-analysis. Protocol registration PROSPERO CRD4201300444 5 (http://www.crd.york.ac.uk/prospero/). STUDY SELECTION: Randomised controlled trials (RCTs) comparing physical activity interventions with placebo, no/or minimal intervention in community-dwelling adults with symptomatic knee or hip osteoarthritis. Primary outcomes were change in physical activity or cardiopulmonary fitness after a minimum follow-up of 6 months. DATA EXTRACTION: Outcomes were measures of physical activity (self-reported and objectively measured) and cardiovascular fitness. Standard mean differences between postintervention values were used to describe the effect sizes. RESULTS: 27,984 titles were screened and 180 papers reviewed in full. Eleven RCTs satisfied inclusion criteria, total study population of 2741 participants, mean age 62.2. The commonest reasons for study exclusion were follow-up less than 6 months and no physical activity measures. The majority of included interventions implement an arthritis self-management programme targeting coping skills and self-efficacy. Seven studies used self-report measures, the pooled effect of these studies was small with significant heterogeneity between studies (SMD 0.22 with 95% CI -0.11 to 0.56, z=1.30 (p=0.19) I(2) statistic of 85%). Subgroup analysis of 6-12 month outcome reduced heterogeneity and increased intervention effect compared to control (SMD 0.53, 95% CI 0.41 to 0.65, z=8.84 (p<0.00001) I(2) of 66%). CONCLUSIONS: Arthritis self-management programmes achieve a small but significant improvement in physical activity in the short term. Effectiveness of intervention declines with extended follow-up beyond 12 months with no significant benefit compared to control. The small number of studies (11 RCTs) limited ability to define effective delivery methods. Investigation of behavioural lifestyle interventions for lower limb osteoarthritis populations would benefit from consensus on methodology and outcome reporting. This includes use of validated physical activity reporting tools and planning for long-term follow-up. PMID- 26260349 TI - A journey into a Mediterranean diet and type 2 diabetes: a systematic review with meta-analyses. AB - OBJECTIVES: To summarise the evidence about the efficacy of a Mediterranean diet on the management of type 2 diabetes and prediabetic states. DESIGN: A systematic review of all meta-analyses and randomised controlled trials (RCTs) that compared the Mediterranean diet with a control diet on the treatment of type 2 diabetes and prediabetic states was conducted. Electronic searches were carried out up to January 2015. Trials were included for meta-analyses if they had a control group treated with another diet, if they were of sufficient duration (at least 6 months), and if they had at least 30 participants in each arm. A random-effect model was used to pool data. PARTICIPANTS: Adults with or at risk for type 2 diabetes. INTERVENTIONS: Dietary patterns that described themselves as using a 'Mediterranean' dietary pattern. OUTCOME MEASURES: The outcomes were glycaemic control, cardiovascular risk factors and remission from the metabolic syndrome. RESULTS: From 2824 studies, 8 meta-analyses and 5 RCTs were eligible. A 'de novo' meta-analysis of 3 long-term (>6 months) RCTs of the Mediterranean diet and glycaemic control of diabetes favoured the Mediterranean diet as compared with lower fat diets. Another 'de novo' meta-analysis of two long-term RCTs showed a 49% increased probability of remission from the metabolic syndrome. 5 meta analyses showed a favourable effect of the Mediterranean diet, as compared with other diets, on body weight, total cholesterol and high-density lipoprotein cholesterol. 2 meta-analyses demonstrated that higher adherence to the Mediterranean diet reduced the risk of future diabetes by 19-23%. CONCLUSIONS: The Mediterranean diet was associated with better glycaemic control and cardiovascular risk factors than control diets, including a lower fat diet, suggesting that it is suitable for the overall management of type 2 diabetes. PMID- 26260352 TI - Cerebrovascular injury as a risk factor for amyotrophic lateral sclerosis. AB - OBJECTIVE: To use an unbiased method to test a previously reported association between cerebral arteriovenous malformation (AVM) embolisation and the subsequent development of amyotrophic lateral sclerosis (ALS). METHODS: A hospital record linkage database was used to create cohorts of individuals coded as having cerebral and peripheral vessel AVMs, stroke (separately for haemorrhagic and ischaemic), transient ischaemic attack (TIA) and subarachnoid haemorrhage (SAH). The rate ratio for subsequent ALS was compared to a reference cohort. RESULTS: An increased rate ratio for ALS was found in relation to prior AVM (2.69; p=0.005), all strokes (1.38; p<0.001), and TIA (1.47; p<0.001). CONCLUSIONS: Cerebrovascular injury from a variety of causes, rather than the presence of AVM or the associated embolisation procedure per se, may be a risk factor for ALS within the context of a more complex multiple-hit model of pathogenesis. PMID- 26260350 TI - A police education programme to integrate occupational safety and HIV prevention: protocol for a modified stepped-wedge study design with parallel prospective cohorts to assess behavioural outcomes. AB - INTRODUCTION: Policing practices are key drivers of HIV among people who inject drugs (PWID). This paper describes the protocol for the first study to prospectively examine the impact of a police education programme (PEP) to align law enforcement and HIV prevention. PEPs incorporating HIV prevention (including harm reduction programmes like syringe exchange) have been successfully piloted in several countries but were limited to brief pre-post assessments; the impact of PEPs on policing behaviours and occupational safety is unknown. OBJECTIVES: Proyecto ESCUDO (SHIELD) aims to evaluate the efficacy of the PEP on uptake of occupational safety procedures, as assessed through the incidence of needle stick injuries (NSIs) (primary outcome) and changes in knowledge of transmission, prevention and treatment of HIV and viral hepatitis; attitudes towards PWID, adverse behaviours that interfere with HIV prevention and protective behaviours (secondary outcomes). METHODS/ANALYSIS: ESCUDO is a hybrid type I design that simultaneously tests an intervention and an implementation strategy. Using a modified stepped-wedge design involving all active duty street-level police officers in Tijuana (N = ~ 1200), we will administer one 3 h PEP course to groups of 20-50 officers until the entire force is trained. NSI incidence and geocoded arrest data will be assessed from department-wide de-identified data. Of the consenting police officers, a subcohort (N=500) will be randomly sampled from each class to undergo pre-PEP and post-PEP surveys with a semiannual follow-up for 2 years to assess self-reported NSIs, attitudes and behaviour changes. The impact on PWIDs will be externally validated through a parallel cohort of Tijuana PWIDs. ETHICS/DISSEMINATION: Research ethics approval was obtained from the USA and Mexico. Findings will be disseminated through open access to protocol materials through the Law Enforcement and HIV Network. TRIAL REGISTRATION NUMBER: NCT02444403. PMID- 26260353 TI - Unpacking the associations between heterogeneous externalising symptom development and academic attainment in middle childhood. AB - This study explores children's externalising symptom development pathways between 8 and 11 years of age (three time points across 2 years) and examines their sociodemographic correlates and associations with change in academic attainment. Externalising symptoms were assessed for 5485 children across three consecutive years (M age = 8.7 years, SD = 0.30 at time 1). National standardised test scores served as an index of academic attainment. Using latent class growth analysis, six distinct trajectories of externalising symptom development were identified. Children who showed increasing externalising symptomatology across the three time points were more likely to be male or have special educational needs. These derived trajectories differentially predicted children's subsequent academic attainment (controlling for earlier attainment). Children with increasing externalising symptomatology were significantly more likely to demonstrate negative change in academic achievement compared with children with consistently low externalising problems. The study helps to clarify the longitudinal association between externalising symptom development and academic attainment, and highlights the importance of early intervention for children with increasing externalising symptoms across middle childhood. PMID- 26260354 TI - Saccharomyces boulardii and bismuth subsalicylate as low-cost interventions to reduce the duration and severity of cholera. AB - We conducted a randomised single-blinded clinical trial of 100 cholera patients in Port-au-Prince, Haiti to determine if the probiotic Saccharomyces cerevisiae var. boulardii and the anti-diarrhoeal drug bismuth subsalicylate (BS) were able to reduce the duration and severity of cholera. Subjects received either: S. boulardii 250 mg, S. boulardii 250 mg capsule plus BS 524 mg tablet, BS 524 mg, or two placebo capsules every 6 hours alongside standard treatment for cholera. The length of hospitalisation plus the number and volume of emesis, stool and urine were recorded every 6 hours until the study subject was discharged (n = 83), left against medical advice (n = 11), or requested removal from the study (n = 6). There were no reported deaths or adverse study-related events. There were no statistically significant differences between the study arms and the outcomes of interest. PMID- 26260355 TI - Epidemiology and risk factors for faecal extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) carriage derived from residents of seven nursing homes in western Shanghai, China. AB - Nursing homes (NHs) have been implicated as significant reservoirs of antibiotic resistant organisms causing severe infectious disease. We investigated the prevalence and molecular epidemiology of, and risk factors for, faecal carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E). A multicentre cross-sectional study was conducted in seven NHs in Shanghai between March 2014 and May 2014. Antimicrobial susceptibility testing and polymerase chain reaction were used to detect genes coding for ESBLs and carbapenemases. NH records at individual-resident level and facility level were examined for potential risk factors. Four hundred and fifty-seven Enterobacteriaceae isolates were collected of which 183 (46.92%) were colonized by ESBL-E. CTX-M enzymes (198/200, 99%) predominated, with CTX-M-14 (84/200, 42%) the most common types. Two carbapenemase producers harboured blaKPC-2. Resistance rates to carbapenems, TZP, AK, FOS, CL and TGC were low. History of invasive procedures [odds ratio (OR) 2.384, 95% confidence interval (CI) 1.318-4.310, P = 0.004], narrow-spectrum cephalosporins (OR 1.635, 95% CI 1.045-2.558, P = 0.031) and broad-spectrum cephalosporins (OR 3.276, 95% CI 1.278-8.398, P = 0.014) were independently associated with ESBL-E carriage. In conclusion, NH residents have a very high prevalence of faecal carriage of ESBL-E. Continuous and active surveillance is important, as are prudent infection control measures and antibiotic use to prevent and control the spread of these antibiotic-resistant strains. PMID- 26260356 TI - Retrospective evaluation of the effect of antivenom administration on hospitalization duration and treatment cost for dogs envenomated by Crotalus viridis: 113 dogs (2004-2012). AB - OBJECTIVE: To compare the effect of antivenom administration on mortality, hospitalization duration, and cost of hospitalization for dogs envenomated by Crotalus viridis. DESIGN: Retrospective study (January 2004-December 2012). SETTING: Private veterinary emergency and referral center. ANIMALS: One hundred thirteen dogs with confirmed C. viridis envenomation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Dogs were divided into groups treated with either supportive care only (group 1) or supportive care plus antivenin crotalidae polyvalent (group 2). A modified snakebite severity score was used to compare patients from group 1 and group 2. Patients in group 2 received one 10 mL vial of antivenin crotalidae polyvalent over 4-6 hours. The mortality rate was 1.8% (2/113). Group 1 had a median duration of hospitalization of 20 hours (range, 8 50 hours), while group 2 had a median duration of hospitalization of 24 hours (range, 1.5-74 hours). Group 1 had a median cost of hospitalization of 1050.00 USD (range, 423.52-2266.09 USD) while group 2 had a median cost of hospitalization of 2002.19 USD (range, 1139.91-6908.01 USD). Both the duration of hospitalization (P < 0.01) and the cost of hospitalization (P < 0.01) were significantly greater in the group of dogs receiving antivenom. CONCLUSIONS: Both the cost and the duration of hospitalization were significantly greater in the group of dogs that received antivenom. The difference in cost between the groups was approximately the cost of the antivenom vial and administration. Amongst the parameters evaluated, no significant benefit was associated with antivenom administered to dogs envenomated by C. viridis. PMID- 26260357 TI - Combined pars plana vitrectomy-scleral buckle versus pars plana vitrectomy for proliferative vitreoretinopathy. AB - The purpose of the study is to evaluate the surgical outcomes of combined pars plana vitrectomy-scleral buckle (PPV-SB) versus pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment complicated with proliferative vitreoretinopathy (PVR). One thousand one hundred and seventy four patients with rhegmatogenous retinal detachment surgery between January 2002 and December 2013 were retrospectively reviewed. Patients with grade C PVR treated with either combined PPV-SB or PPV alone were included in the study. Study outcomes included single surgery anatomic success rate and postoperative visual outcome at 12 months postoperatively. Seventy-seven patients with grade C PVR were identified for analysis. At the end of 12-month follow-up, 80.5 % eyes (33/41) in the PPV-SB group and 58.3 % eyes (21/36) in the PPV group achieved single surgery anatomical success. In a multiple logistic regression model, none of the baseline variables (age, gender, macula status, grade of PVR, extent of detachment, presence of vitreous hemorrhage, lens status, status of high myopia) nor types of retinal detachment surgery (use of scleral buckle, barrier endolaser, 360 degree endolaser, cryopexy, retinectomy, tamponade agent, phacoemulsification) had significant effect on single surgery anatomical success. The post-treatment mean logMAR visual acuity of the PPV-SB group was 1.58 +/- 0.58 and the PPV group was 1.57 +/- 0.61. There was no significant difference in the postoperative visual acuity between the two groups (P = 0.849). For patients with grade C PVR, PPV-SB did not demonstrate a superiority over PPV alone in achieving single surgery anatomical success. PMID- 26260358 TI - In vitro study of cyclosporine A 0.05 % on primary and recurrent pterygium fibroblasts. AB - To compare the cyclosporine 0.05 % exposure effect on fibroblasts from primary and recurrent pterygium. Primary culture of fibroblasts from primary and recurrent pterygium was performed until the third passage, which was exposed to cyclosporine 0.05 % in a group and the other remaining unexposed (control group), in triplicates. After 3, 6, 12, and 17 days of exposure the viable cell counting was performed by hemocytometer. The results were statistically analyzed using the technique of analysis of non-parametric variance model for repeated measures with three factors. There was a significant reduction in both fibroblast proliferation, in primary as in the recurrent pterygium cultures exposed to cyclosporine when compared not exposed cultures, with statistical significance (P < 0.05). Comparing primary and recurrent pterygium that received the drug, there was no significant difference in cell proliferation in relation to primary or recurrent pterygium. Cyclosporine 0.05 % is effective in inhibiting fibroblast proliferation in culture, both in primary and as in recurrent pterygium. PMID- 26260359 TI - Nanoemulsion-templated polylelectrolyte multifunctional nanocapsules for DNA entrapment and bioimaging. AB - The emerging field of bionanotechnology aims at advancing colloidal and biomedical research via introduction of multifunctional nanoparticle-based containers intended for both gene therapy and bioimaging. In the present contribution we entrapped the model genetic material (herring testes DNA) in the newly-designed non-viral vectors, i.e., multifunctional nanocapsules obtained by layer-by-layer (LbL) adsorption of DNA and oppositely charged polysaccharide based chitosan (CHIT) on the nanoemulsion core, loaded by IR-780 indocyanine (used as the fluorescent marker) and stabilized by gemini-type ammonium salts: N,N,N',N'-tetramethyl-N,N'-di(dodecyl)-ethylenediammonium bromide, d(DDA)PBr and N,N,N',N'-tetramethyl-N,N'-di(dodecyl)-butylenediammonium d(DDA)BBr. Ternary phase diagrams of the surfactant-oil-water systems were determined by titration method. Then, the stability of the nanoemulsions obtained with IR-780 solubilized in the oleic acid (OA) or isopropyl myristate (IPM) phase was evaluated by backscattering (BS) profiles and zeta-potential measurements. In the next step, CHIT and DNA layers were subsequently deposited on the kinetically stable nanoemulsion cores. The IR-780-loaded nanocarriers covered by (DNA/CHIT)4 bilayers shown the high zeta-potential value (about +43mV provided by Doppler electrophoresis), the size <120nm and the spherical shape as analyzed by dynamic light scattering (DLS), atomic force microscopy (AFM) and scanning electron microscopy (SEM). Finally, the long-lasting nanosystems were subjected to in vitro biological studies on human cancer cell lines - doxorubicin-sensitive breast (MCF-7/WT), epithelial lung adenocarcinoma (A549) and skin melanoma (MEWO). Biological response of the cell culture was expressed as cytotoxic activity evaluated by MTT-based proliferation assay as well as bioimaging of intracellular localization of IR-780 molecules loaded in the multilayer DNA deposited nanocontainers - provided by confocal laser scanning microscopy (CLSM) and total internal reflection fluorescence microscopy (TIRFM). Our results demonstrate that the fabricated oil-core CHIT-coated nanocapsules stabilized by both d(DDA)PBr and d(DDA)BBr surfactants are promising as multifunctional nanocarriers for DNA delivery and cancer diagnostics. PMID- 26260360 TI - Human GPR42 is a transcribed multisite variant that exhibits copy number polymorphism and is functional when heterologously expressed. AB - FFAR3 (GPR41) is a G-protein coupled receptor for which short-chain fatty acids serve as endogenous ligands. The receptor is found on gut enteroendocrine L cells, pancreatic beta-cells, and sympathetic neurons, and is implicated in obesity, diabetes, allergic airway disease, and altered immune function. In primates, FFAR3 is segmentally duplicated resulting in GPR42, a gene currently classified as a suspected pseudogene. In this study, we sequenced FFAR3 and GPR42 open reading frames from 56 individuals and found an unexpectedly high frequency of polymorphisms contributing to several complex haplotypes. We also identified a frequent (18.8%) structural variation that results in GPR42 copy number polymorphism. Finally, sequencing revealed that 50.6% of GPR42 haplotypes differed from FFAR3 by only a single non-synonymous substitution and that the GPR42 reference sequence matched only 4.4% of the alleles. Sequencing of cDNA from human sympathetic ganglia and colon revealed processed transcripts matching the GPR42 genotype. Expression of several GPR42 haplotypes in rat sympathetic neurons revealed diverse pharmacological phenotypes that differed in potency and efficacy. Our data suggest that GPR42 be reclassified as a functioning gene and that recognition of sequence and copy number polymorphism of the FFAR3/GPR42 complex be considered during genetic and pharmacological investigation of these receptors. PMID- 26260361 TI - Shared decision making for psychiatric medication management: beyond the micro social. AB - BACKGROUND: Mental health care has lagged behind other health-care domains in developing and applying shared decision making (SDM) for treatment decisions. This is despite compatibilities with ideals of modern mental health care such as self-management and recovery-oriented practice, and growing policy-level interest. Psychiatric medication is a mainstay of mental health treatment, but there are known problems with prescribing practices, and service users report feeling uninvolved in medication decisions and concerned about adverse effects. SDM has potential to produce better tailoring of psychiatric medication to individuals' needs. OBJECTIVES: This conceptual review argues that several aspects of mental health care that differ from other health-care contexts (e.g. forms of coercion, questions about service users' insight and disempowerment) may impact on processes and possibilities for SDM. It is therefore problematic to uncritically import models of SDM developed in other health-care contexts. We argue that decision making for psychiatric medication is better understood in a broader way that moves beyond the micro-social focus of a medical consultation. Contextualizing specific medication-related consultations within longer term relationships, and broader service systems enables recognition of the multiple processes, actors and agendas that shape how psychiatric medication is prescribed, managed and used, and which may facilitate or impede SDM. CONCLUSION: A broad conceptualization of decision making for psychiatric medication that moves beyond the micro-social can account for why SDM in this domain remains a rarity. It has both conceptual and practical utility for evaluating research evidence, identifying future research priorities and highlighting fruitful ways of developing and implementing SDM in mental health care. PMID- 26260362 TI - Formation and elimination of pyrraline in the Maillard reaction in a saccharide lysine model system. AB - BACKGROUND: Pyrraline, a causative factor for various kinds of disease, is also used as a food contaminant to evaluate the formation of advanced glycation end products (AGEs) in diet foods. In this study, model systems consisting of lysine and different saccharides were heated at different times, temperatures and initial molar ratios of saccharide to lysine under microwave heating conditions in order to investigate the formation of pyrraline. RESULTS: Increase in initial molar ratio of saccharide to lysine could significantly promote the formation of pyrraline. Specifically, the pyrraline formation rate was influenced by the structure of saccharides involved in the reaction, and decreased in the following order: lactose > fructose > glucose > sucrose; the highest pyrraline was generated in lactose-lysine models. The maximum pyrraline was formed at 140 degrees C. Moreover, saccharides and lysine had different effects on the stability of pyrraline. Among the reactants, lysine was the major factor for the instability of pyrraline; a dipyrraline and a crosslink by pyrraline reacting with lysine could be formed. CONCLUSION: Pyrraline formation by the saccharide lysine model system was a dynamic reaction, consisting not only of the pyrraline formation, but also pyrraline elimination with some formation of crosslinks. (c) 2015 Society of Chemical Industry. PMID- 26260363 TI - A duplication upstream of SOX9 was not positively correlated with the SRY negative 46,XX testicular disorder of sex development: A case report and literature review. AB - The 46,XX male disorder of sex development (DSD) is rarely observed in humans. Patients with DSD are all male with testicular tissue differentiation. The mechanism of sex determination and differentiation remains to be elucidated. In the present case report, an 46,XX inv (9) infertile male negative for the sex determining region of the Y chromosome (SRY) gene was examined. This infertile male was systemically assessed by semen analysis, serum hormone testing and gonadal biopsy. Formalin-fixed and paraffin-embedded gonad tissues were assessed histochemically. The SRY gene was analyzed by fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR). The other 23 specific loci, including the azoospermia factor region on the Y chromosome and the sequence-targeted sites of the SRY-box 9 (SOX9) gene were analyzed by PCR. The genes RSPO1, DAX1, SOX3, ROCK, DMRT1, SPRY2 and FGF9 were also assessed using sequencing analysis. Affymetrix Cytogenetics Whole Genome 2.7 M Arrays were used for detecting the genomic DNA from the patient and the parents. The patient with the 46,XX inv (9) (p11q13) karyotype exhibited male primary, however, not secondary sexual characteristics. However, the patient's mother with the 46, XX inv (9) karyotype was unaffected. The testicular tissue dysplasia of the patient was confirmed by tissue biopsy and absence of the SRY gene, and the other 23 loci on the Y chromosome were confirmed by FISH and/or PCR. The RSPO1, DAX1, SOX3, ROCK, DMRT1, SPRY2 and FGF9 genes were sequenced and no mutations were detected. A duplication on the 3 M site in the upstream region of SOX9 was identified in the patient as well as in the mother. The patient with the 46,XX testicular DSD and SRY-negative status was found to be infertile. The duplication on the 3 M site in the upstream region of SOX9 was a polymorphism, which indicated that the change was not a cause of 46,XX male SDS. These clinical, molecular and cytogenetic findings suggested that other unidentified genetic or environmental factors are significant in the regulation of SDS. PMID- 26260364 TI - Facial Soft Tissue Thickness Among Three Skeletal Classes in Adult Pakistani Subjects. AB - Different facial reconstruction methods rely on the average facial soft tissue thickness values provided in previous studies. Facial soft tissue thickness is influenced by the age, sex, and ethnicity of the individual. The aim of the present study was to determine facial soft tissue thickness of adult Pakistani subjects with different facial morphology. A total of 166 subjects were categorized into three skeletal classes (based on convex, straight, or concave facial profile) employing the classification system used in orthodontics. Facial soft tissue thickness was determined at ten midline points on lateral cephalograms. Significant differences in facial soft tissue thickness were present at glabella, labrale superius, stomion, and labiomentale in males and at labrale superius, labrale inferius, labiomentale, and pogonion in females among different skeletal classes. The current study suggests that the skull morphology related variations in facial soft tissue thickness should be considered during facial reconstruction to achieve accurate results. PMID- 26260365 TI - Enhanced astroglial GABA uptake in heart failure. PMID- 26260368 TI - Pancreas: Fatty pancreas linked to increased BMI and insulin resistance in children. PMID- 26260366 TI - Extraintestinal manifestations of coeliac disease. AB - Coeliac disease is a common disorder that can arise at any age and typically presents with a broad spectrum of symptoms. The disease is thought to be underdiagnosed, in part owing to the fact that coeliac disease is often characterized by associated conditions and extraintestinal manifestations that can misdirect and impede diagnosis. Some of these manifestations are direct consequences of autoimmunity, such as dermatitis herpetiformis or gluten ataxia, whereas others are indirectly related to inflammation and/or malabsorption including anaemia, osteoporosis, short stature and delayed puberty. Any organ from the central nervous system to joints, liver or teeth can be affected. In some cases, extraintestinal symptoms are the only clinical manifestations of coeliac disease or occur in conjunction with diarrhoea and malabsorptive symptoms. An increased awareness among medical practitioners of the variety of extraintestinal manifestations of coeliac disease is essential to improve diagnosis and treatment. PMID- 26260371 TI - Barrett oesophagus: Tracing the genetic pathway to oesophageal cancer. PMID- 26260369 TI - Optimizing early upper gastrointestinal cancer detection at endoscopy. AB - Survival rates for upper gastrointestinal cancers are poor and oesophageal cancer incidence is increasing. Upper gastrointestinal cancer is also often missed during examinations; a predicament that has not yet been sufficiently addressed. Improvements in the detection of premalignant lesions, early oesophageal and gastric cancers will enable organ-preserving endoscopic therapy, potentially reducing the number of advanced upper gastrointestinal cancers and resulting in improved prognosis. Japan is a world leader in high-quality diagnostic upper gastrointestinal endoscopy and the clinical routine in this country differs substantially from Western practice. In this Perspectives article, we review lessons learnt from Japanese gastroscopy technique, training and screening for risk stratification. We suggest a key performance indicator for upper gastrointestinal endoscopy with a minimum total procedure time of 8 min, and examine how quality assurance concepts in bowel cancer screening in the UK could be applied to upper gastrointestinal endoscopy and improve clinical practice. PMID- 26260373 TI - Liver: A new copper cut-off value for diagnosis of Wilson disease? PMID- 26260375 TI - The influence of simultaneous integrated boost, hypofractionation and oncoplastic surgery on cosmetic outcome and PROMs after breast conserving therapy. AB - INTRODUCTION: We retrospectively investigated the possible influence of a simultaneous integrated boost (SIB), hypofractionation and oncoplastic surgery on cosmetic outcome in 125 patients with stage I-II breast cancer treated with breast conserving therapy (BCT). PATIENTS AND METHODS: The boost was given sequentially (55%) or by SIB (45%); fractionation was conventional (83%) or hypofractionated (17%); the surgical technique was a conventional lumpectomy (74%) or an oncoplastic technique (26%). We compared cosmetic results subjectively using a questionnaire independently completed by the patient and by the physician and objectively with the BCCT.core software. Independent-samples T tests were used to compare outcome in different groups. Patients also completed the EORTC QLQ C30 and BR23. RESULTS: Univariate analyses indicated no significant differences of the cosmetic results (P <= 0.05) for the type of boost or fractionation. However, the conventional lumpectomy group scored significantly better than the oncoplastic group in the BCCT.core evaluation, without a significant difference in the subjective cosmetic evaluation. Quality of life outcome was in favour of SIB, hypofractionation and conventional surgery. CONCLUSION: Our study indicates that the current RT techniques seem to be safe for cosmetic outcome and quality of life. Further investigation is needed to verify the possible negative influence of oncoplastic surgery on the cosmetic outcome and the quality of life as this technique is especially indicated for patients with an unfavourable tumour/breast volume ratio. PMID- 26260376 TI - Numerical simulations of a bypass repair of an iliac artery obliteration. PMID- 26260377 TI - Tert-butylhydroquinone Ameliorates Early Brain Injury After Experimental Subarachnoid Hemorrhage in Mice by Enhancing Nrf2-Independent Autophagy. AB - Evidence has shown that the activation of the autophagy pathway after experimental subarachnoid hemorrhage (SAH) protects against neuronal damage. Tert butylhydroquinone (tBHQ), a commonly used nuclear factor erythroid 2-related factor 2 (Nrf2) activator, was found to significantly enhance autophagy activation. The aim of this study was to explore the effect of tBHQ treatment on early stage brain injury at 24 h after SAH. The results showed that tBHQ treatment failed to stimulate an effective anti-oxidative effect at 24 h after the SAH operation, but succeeded in ameliorating early brain injury, including alleviated brain edema, BBB disruption, neuronal degeneration and neurological deficits. Further exploration found that tBHQ treatment significantly increased the expression of Beclin-1 and the ratio of microtubule-associated protein 1 light chain 3 (LC3)-II to LC3-I, suggesting that autophagy was enhanced after tBHQ treatment. Moreover, tBHQ treatment restored Bcl-2 and Bax expression and reduced caspase-3 cleavage, suggesting the protective effect of tBHQ treatment in ameliorating brain injury after SAH. Furthermore, tBHQ enhanced autophagy activation, decreased neuronal degeneration and improved the neurological score after SAH in Nrf2-deficient mice. Taken together, these findings suggest that tBHQ treatment exerts neuro-protective effects against EBI following SAH by enhancing Nrf2-independent autophagy. Therefore, tBHQ is a promising therapeutic agent against EBI following SAH. PMID- 26260378 TI - [Factors determining patient satisfaction with the pre-anaesthesia consultation]. AB - OBJECTIVE: To analyse patient satisfaction with care provided in the pre anaesthetic consultation and its determining factors. MATERIAL AND METHOD: An anonymous questionnaire was randomly distributed to patients attending a pre anaesthesia clinic, which included 4 questions with 5 possible answers on a (very dissatisfied, dissatisfied, fairly satisfied, satisfied and very satisfied) categorical graduated scale related to punctuality, understanding of the information received, respectful treatment, and overall satisfaction. The fifth question was about the knowledge or the name of the anaesthesiologist who attended them. A binary logistic regression model was used, which identified the predictors of satisfaction, calculated the odds ratios, and their respective 95% confidence intervals. RESULTS: A total of 4006 questionnaires were analysed, in which 99.2% (3966) of users rated as satisfied/very satisfied the question about the respectful treatment, 98.4% (3937) of the information received and understanding, 77.4% (3096) punctuality in attending, and 97, 6% (3909) overall satisfaction. Almost three-quarters (71%, 2844) did not know the name of the anaesthesiologist. Regression analysis associated the more satisfied with their treatment (OR 17.44; P<.0005) and the information received (OR 14.94, P<.0005), while punctuality (OR 5 40; P<.0005) was the factor that contributed less to the result. CONCLUSION: In our population satisfaction in pre-anaesthesia consultation is due mainly to the communication skills of the anaesthesiologist. PMID- 26260379 TI - Drugs as risk factors of acute kidney injury in critically ill children. AB - BACKGROUND: Acute kidney injury (AKI) is a serious condition in critically ill children. Nephrotoxic medication exposure is a common contributing factor to AKI, but little literature is available in pediatrics. The aim of the present study was to assess potential associations between drugs and the risk of developing AKI. METHODS: We performed a retrospective case-control study in a pediatric intensive care unit (PICU). Cases were patients who developed AKI during PICU stay. Patients without AKI served as controls and were matched to cases by age and gender in a one-to-one ratio. RESULTS: One hundred case-control pairs were included. Cases were not statistically different from controls with regard to median weight and main diagnoses, but differed with regard to the need for mechanical ventilation, severity of illness, and median length of PICU stay. Multivariate models revealed a statistically significant higher risk of developing AKI for patients treated with metamizole, morphine, paracetamol, and tropisetron. A similar risk could be shown for medication groups, namely glucocorticoids, betalactam antibiotics, opioids, and non-steroidal anti inflammatory drugs. CONCLUSIONS: The results suggest that drugs are associated with acute renal dysfunction in critically ill children, but the multifactorial causes of AKI should be kept in mind. PMID- 26260380 TI - Refractory arterial hypertension and renal failure combined with cerebral seizures and pancytopenia in a 5-year-old girl with bilateral nephromegaly: Questions. PMID- 26260381 TI - Refractory arterial hypertension and renal failure combined with cerebral seizures and pancytopenia in a 5-year-old girl with bilateral nephromegaly: Answers. PMID- 26260383 TI - Commonality of rituximab pharmacokinetic disposition in nephrotic syndrome and autoimmune cytopenias in chronic lymphocytic leukemia patients. PMID- 26260382 TI - Hepatorenal fibrocystic diseases in children. AB - BACKGROUND: Hepatorenal fibrocystic diseases (HRFCDs) are a group of monogenic disorders characterized by developmental abnormalities involving the liver and kidney. In this study, we performed genotype and phenotype analyses of children with HRFCDs to determine the distribution of underlying diseases. METHODS: A total of 36 children with HRFCDs were recruited, with genetic tests being performed in 22 patients and 14 patients diagnosed clinically as having autosomal recessive polycystic kidney disease (ARPKD). RESULTS: In children with HRFCDs, ARPKD was the most common disease, found in 16/36 (44.4 %), followed by nephronophthisis 13 (NPHP13) in 11/36 (30.6 %) and Meckel-Gruber syndrome type 3 (MKS3) in 4/36 (11.1 %). Renal function deteriorated faster in children with NPHP13. The main hepatic pathology was Caroli disease in the NPHP13 patients, while most other patients had Caroli syndrome or congenital hepatic fibrosis. Of note, three of four MKS3 patients had an accompanying choledochal cyst. No ARPKD patient had other organ involvement, while several NPHP13 patients had ocular and/or neurodevelopmental involvement. In contrast, all MKS3 patients had severe ocular and neurodevelopmental involvement. CONCLUSIONS: NPHP13 is a major disease in the HRFCD category, and thorough evaluation of its clinical features, including kidney, liver and other organ involvement, may aid in the differential diagnosis of HRFCD. PMID- 26260384 TI - Race and ethnicity considerations in GI endoscopy. PMID- 26260385 TI - The role of endoscopy in ampullary and duodenal adenomas. PMID- 26260386 TI - Illness and artistic creativity (on the 70th anniversary of the death of Bela Bartok, composer, ethnomusicologist and leukemia patient). PMID- 26260387 TI - The novel function of CD82 and its impact on BCL2L12 via AKT/STAT5 signal pathway in acute myelogenous leukemia cells. AB - The aim of this study was to explore the biological functions of a tetraspanin family protein CD82 expressed aberrantly in chemotherapy-resistant CD34(+)/CD38( ) acute myelogenous leukemia (AML) cells. Microarray analysis of patient-isolated CD34(+)/CD38(-) AML cells revealed that the levels of anti-apoptotic protein BCL2L12 were downregulated after CD82 depletion by specific short hairpin RNA (shRNA). Western blot analysis indicated that BCL2L12 was aberrantly expressed in patient-isolated AML cells and AML cell lines. Furthermore, CD82 blockade by a specific antibody downregulated BCL2L12 in parallel with dephosphorylation of signal transducer and activator of transcription 5 (STAT5) and AKT, whereas pharmacological inhibition of STAT5 and AKT activation decreased BCL2L12 expression in leukemia cells. In addition, shRNA-mediated downregulation of BCL2L12 increased the levels of cleaved caspase-3 and suppressed proliferation of leukemia cells, impairing their engraftment in immunodeficient mice. Taken together, our results indicate that CD82 regulated BCL2L12 expression via STAT5A and AKT signaling and stimulated proliferation and engrafting of leukemia cells, suggesting that CD82 and BCL2L12 may be promising therapeutic targets in AML. PMID- 26260388 TI - Characterization of the chromosomal integration of Saccharopolyspora plasmid pCM32 and its application to improve production of spinosyn in Saccharopolyspora spinosa. AB - Saccharopolyspora spinosa produces tetra-cyclic macrolide spinosyns, a group of highly efficient pesticidal agents. However, this species lacks efficient vectors for genetic manipulation. In this study, the circular plasmid pCM32 was newly isolated from Saccharopolyspora endophytica YIM 61095. The complete nucleotide sequence of pCM32 consists of 14,611 bp and is predicted to encode 17 open reading frames (ORFs). Interestingly, a putative int gene in pCM32 was predicted by homologous alignment to encode an integrase belonging to the tyrosine family of integrases/recombinases. Plasmid pCM238 containing this int locus derived from pCM32 could be transferred by conjugation from Escherichia coli into Sa. spinosa at a high frequency. Integration of pCM238 in the host chromosome was demonstrated as site-specific recombination (at the tRNA (Ser) gene) via a 56-bp core sequence within the attP/attB sites. Plasmid pCM265, a shuttle vector containing the int and attP sequences of pCM32, was constructed to introduce foreign genes into Sa. spinosa. The production of spinosad approximately doubled in Sa. spinosa NRRL18395 after introducing pCM265-derived plasmids carrying the genes for phosphofructokinase (PFK) or anthranilate synthase. These results indicate that plasmid pCM32 is an actinomycete integrative and conjugative element (AICE) and that its derived integrative vectors are useful for efficiently introducing foreign DNA into Sa. spinosa. PMID- 26260389 TI - Enduring Elevations of Hippocampal Amyloid Precursor Protein and Iron Are Features of beta-Amyloid Toxicity and Are Mediated by Tau. AB - The amyloid cascade hypothesis of Alzheimer's disease (AD) positions tau protein as a downstream mediator of beta-amyloid (Abeta) toxicity This is largely based on genetic cross breeding, which showed that tau ablation in young (3-7-month old) transgenic mice overexpressing mutant amyloid precursor protein (APP) abolished the phenotype of the APP AD model. This evidence is complicated by the uncertain impact of overexpressing mutant APP, rather than Abeta alone, and for potential interactions between tau and overexpressed APP. Cortical iron elevation is also implicated in AD, and tau promotes iron export by trafficking APP to the neuronal surface. Here, we utilized an alternative model of Abeta toxicity by directly injecting Abeta oligomers into the hippocampus of young and old wild type and tau knockout mice. We found that ablation of tau protected against Abeta induced cognitive impairment, hippocampal neuron loss, and iron accumulation. Despite injected human Abeta being eliminated after 5 weeks, enduring changes, including increased APP levels, tau reduction, tau phosphorylation, and iron accumulation, were observed. While the results from our study support the amyloid cascade hypothesis, they also suggest that downstream effectors of Abeta, which propagate toxicity after Abeta has been cleared, may be tractable therapeutic targets. PMID- 26260391 TI - Dentures are a Reservoir for Respiratory Pathogens. AB - PURPOSE: Recent studies have established a relationship between dental plaque and pulmonary infection, particularly in elderly individuals. Given that approximately one in five adults in the UK currently wears a denture, there remains a gap in our understanding of the direct implications of denture plaque on systemic health. The aim of this study was to undertake a comprehensive evaluation of putative respiratory pathogens residing upon dentures using a targeted quantitative molecular approach. MATERIALS AND METHODS: One hundred and thirty patients' dentures were sonicated to remove denture plaque biofilm from the surface. DNA was extracted from the samples and was assessed for the presence of respiratory pathogens by quantitative polymerase chain reaction (qPCR). Ct values were then used to approximate the number of corresponding colony forming equivalents (CFEs) based on standard curves. RESULTS: Of the dentures, 64.6% were colonized by known respiratory pathogens. Six species were identified: Streptococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Haemophilus influenzae B, Streptococcus pyogenes, and Moraxella catarrhalis. P. aeruginosa was the most abundant species followed by S. pneumoniae and S. aureus in terms of average CFE and overall proportion of denture plaque. Of the participants, 37% suffered from denture stomatitis; however, there were no significant differences in the prevalence of respiratory pathogens on dentures between healthy and inflamed mouths. CONCLUSIONS: Our findings indicate that dentures can act as a reservoir for potential respiratory pathogens in the oral cavity, thus increasing the theoretical risk of developing aspiration pneumonia. Implementation of routine denture hygiene practices could help to reduce the risk of respiratory infection among the elderly population. PMID- 26260392 TI - Little effect of natural noise on high-frequency hearing in frogs, Odorrana tormota. AB - Ambient noise influences acoustic communication in animals. The concave-eared frogs (Odorrana tormota) produce high-frequency sound signals to avoid potential masking from noise. However, whether environmental noise has effect on the high frequency hearing of frogs is largely unclear. By measuring the auditory evoked near-field potentials (AENFPs) from the torus semicircularis of the midbrain at frequencies 1-23 kHz in the presence of three noise levels, we found no significant difference in the peak-to-peak amplitude, threshold and latency of AENFP between low-level (35 dB SPL) background noise and mid-level (65 dB SPL) broadcast natural noise. For a natural noise level of 85 dB SPL, AENFP amplitude decreased and threshold and latency increased at frequencies 3-13 kHz. Spike counts evoked by stimuli at the best excitatory frequency under 85 dB SPL natural noise exposure were lower in 7-kHz CF neurons than in exposures to 35 and 65 dB SPL noise. However spike counts were similar for 14- and 20-kHz CF neurons at the three exposure levels. These findings indicate that environmental noise does not mask the responses of high-frequency tuned auditory neurons, and suggest that the acoustic communication system of O. tormota is efficiently adapted to noisy habitats. PMID- 26260390 TI - Cannabinoids in Neurodegenerative Disorders and Stroke/Brain Trauma: From Preclinical Models to Clinical Applications. AB - Cannabinoids form a singular family of plant-derived compounds (phytocannabinoids), endogenous signaling lipids (endocannabinoids), and synthetic derivatives with multiple biological effects and therapeutic applications in the central and peripheral nervous systems. One of these properties is the regulation of neuronal homeostasis and survival, which is the result of the combination of a myriad of effects addressed to preserve, rescue, repair, and/or replace neurons, and also glial cells against multiple insults that may potentially damage these cells. These effects are facilitated by the location of specific targets for the action of these compounds (e.g., cannabinoid type 1 and 2 receptors, endocannabinoid inactivating enzymes, and nonendocannabinoid targets) in key cellular substrates (e.g., neurons, glial cells, and neural progenitor cells). This potential is promising for acute and chronic neurodegenerative pathological conditions. In this review, we will collect all experimental evidence, mainly obtained at the preclinical level, supporting that different cannabinoid compounds may be neuroprotective in adult and neonatal ischemia, brain trauma, Alzheimer's disease, Parkinson's disease, Huntington's chorea, and amyotrophic lateral sclerosis. This increasing experimental evidence demands a prompt clinical validation of cannabinoid-based medicines for the treatment of all these disorders, which, at present, lack efficacious treatments for delaying/arresting disease progression, despite the fact that the few clinical trials conducted so far with these medicines have failed to demonstrate beneficial effects. PMID- 26260393 TI - Dedicated Perioperative Hip Fracture Comanagement Programs are Cost-effective in High-volume Centers: An Economic Analysis. AB - BACKGROUND: Osteoporotic hip fractures are common injuries typically occurring in patients who are older and medically frail. Studies have suggested that creation of a multidisciplinary team including orthopaedic surgeons, internal medicine physicians, social workers, and specialized physical therapists, to comanage these patients can decrease complication rates, improve time to surgery, and reduce hospital length of stay; however, they have yet to achieve widespread implementation, partly owing to concerns regarding resource requirements necessary for a comanagement program. QUESTIONS/PURPOSES: We performed an economic analysis to determine whether implementation of a comanagement model of care for geriatric patients with osteoporotic hip fractures would be a cost effective intervention at hospitals with moderate volume. We also calculated what annual volume of cases would be needed for a comanagement program to "break even", and finally we evaluated whether universal or risk-stratified comanagement was more cost effective. METHODS: Decision analysis techniques were used to model the effect of implementing a systems-based strategy to improve inpatient perioperative care. Costs were obtained from best-available literature and included salary to support personnel and resources to expedite time to the operating room. The major economic benefit was decreased initial hospital length of stay, which was determined via literature review and meta-analysis, and a health benefit was improvement in perioperative mortality owing to expedited preoperative evaluation based on previously conducted meta-analyses. A break-even analysis was conducted to determine the annual case volume necessary for comanagement to be either (1) cost effective (improve health-related quality of life enough to be worth additional expenses) or (2) result in cost savings (actually result in decreased total expenses). This calculation assumed the scenario in which a hospital could hire only one hospitalist (and therapist and social worker) on a full-time basis. Additionally, we evaluated the scenario where the necessary staff was already employed at the hospital and could be dedicated to a comanagement service on a part-time basis, and explored the effect of triaging only patients considered high risk to a comanagement service versus comanaging all geriatric patients. Finally, probabilistic sensitivity analysis was conducted on all critical variables, with broad ranges used for values around which there was higher uncertainty. RESULTS: For the base case, universal comanagement was more cost effective than traditional care and risk-stratified comanagement (incremental cost effectiveness ratios of USD 41,100 per quality adjusted life-year and USD 81,900 per quality-adjusted life-year, respectively). Comanagement was more cost effective than traditional management as long as the case volume was more than 54 patients annually (range, 41-68 patients based on sensitivity analysis) and resulted in cost savings when there were more than 318 patients annually (range, 238-397 patients). In a scenario where staff could be partially dedicated to a comanagement service, universal comanagement was more cost effective than risk-stratified comanagement (incremental cost effectiveness of USD 2300 per quality-adjusted life-year), and both comanagement programs had lower costs and better outcomes compared with traditional management. Sensitivity analysis was conducted and showed that the level of uncertainty in key variables was not high enough to change the core conclusions of the model. CONCLUSIONS: Implementation of a systems-based comanagement strategy using a dedicated team to improve perioperative medical care and expedite preoperative evaluation is cost effective in hospitals with moderate volume and can result in cost savings at higher-volume centers. The optimum patient population for a comanagement strategy is still being defined. LEVEL OF EVIDENCE: Level 1, Economic and Decision Analysis. PMID- 26260394 TI - A Porcine Knee Model Is Valid for Use in the Evaluation of Arthroscopic Skills: A Pilot Study. AB - BACKGROUND: Previously validated knee arthroscopy evaluation tools have used human cadaveric knees. This is unsustainable because of the cost and scarcity of these specimens. Porcine (pig) knees are anatomically similar, affordable, and easily obtainable; however, whether porcine knees represent a suitable alternative to human specimens has not been evaluated. QUESTIONS/PURPOSES: The purpose of this study was to determine whether porcine knees are similar to human cadaveric knees for the assessment of knee arthroscopy skills by evaluating (1) the validity of the porcine model (whether trainees of the same level of ability scored similarly when using the two models) and (2) the reliability of the porcine model (whether surgeons with experience achieved higher scores than surgeons with less experience in the porcine model). METHODS: Eleven orthopaedic surgery residents (five junior residents and six senior residents), one orthopaedic sports medicine fellow, and three attending orthopaedic surgeons were enrolled. Participants were provided instructions for a proper arthroscopic examination of the knee and asked to identify, and then probe, the listed anatomic structures on both the human and porcine knee specimens. Each participant was asked to demonstrate the following skills: joint manipulation, instrument control and triangulation, fluid management, maintenance of field of view, economy of movement, and efficiency. The Objective Assessment of Arthroscopic Skills (OAAS) and checklist for diagnostic arthroscopy of the knee were used for skills assessment by one observer. Internal consistency, a measure of how well the assessment tool measures the skills being studied, was determined by Cronbach's alpha and group differences investigated by paired t-test and Wilcoxon signed-rank tests where appropriate. Based on a sample size calculation, a total of 37 subjects would be required for the full-scale research study to achieve a power of 0.80, with alpha set at 0.05, to detect a difference in OAAS score of 4.73 (25%). This value is outside of the 95% confidence intervals for the human knee. RESULTS: We found the porcine model to have a high level of face validity. There was no difference with the numbers available in total OAAS scores (mean +/- SD; 95% confidence interval [CI]) within subjects between the human (18.93 +/- 7.54; 14.76-23.11) and porcine (17.87 +/- 6.36; 14.34-21.39) knees (p = 0.433). There was also no difference (p = 0.234) with the numbers available in overall OAAS score among participants working on either human (2.60 +/- 1.35; 1.85-3.35) or porcine (2.33 +/- 0.90; 1.84-2.83) specimens. Internal consistency of the simulation for both the human and porcine knees was high and did not differ between groups (Cronbach's alpha was 0.919 in the human knee and 0.954 in the porcine knee), suggesting the OAAS outcome score specifically assesses arthroscopic skill of participants in both the human and porcine models. More experienced arthroscopists scored higher than did less experienced trainees; there was high correlation (Pearson's correlation coefficient r, 95% CI) between years of experience and total OAAS scores in human (0.78; 0.46-0.92) and porcine (0.80; 0.49-0.93) diagnostic arthroscopy models. CONCLUSIONS: The porcine cadaveric knee model was a valid surrogate for the human knee in arthroscopic skills assessment. CLINICAL RELEVANCE: Trainees can be objectively evaluated using an affordable model that allows summative and formative feedback in the laboratory at a fraction of the cost of previously validated methods. PMID- 26260395 TI - CORR Insights((r)): Backside Wear Is Not Dependent on the Acetabular Socket Design in Crosslinked Polyethylene Liners. PMID- 26260396 TI - Development and Validation of a Distal Embolization Risk Score During Primary Angioplasty in ST-Elevation Myocardial Infarction. AB - This study aims to develop and validate a new angiographic risk score to predict the risk of distal embolization (DE) during primary percutaneous coronary intervention (p-PCI) for ST-elevation myocardial infarction. Study included data from 1,200 patients who underwent p-PCI. The cohort was randomly split into a derivation cohort (n = 814) and a validation cohort (n = 386). Logistic regression was used to examine the relation between risk factors and the occurrence of DE. To each covariate in the model was assigned an integer score based on the regression coefficients. Variables included in the risk score, according to multivariable analysis, were occlusion pattern of infarct-related artery, Thrombolysis In Myocardial Infarction Thrombus Score 2 to 4, reference vessel diameter >=3.5 mm, and lesion length >20 mm. To each variable was assigned a 0- to +2-point score according to the strength of the statistical association. Rates of DE in low-, intermediate-, and high-risk groups were 5.6%, 15.8%, and 40% in the derivation cohort (p for trend <0.0001; C-statistic 0.70) and 7.5%, 12.1%, and 37.9% in the validation cohort (p for trend <0.0001; C-statistic 0.62), respectively. In conclusion, the individual risk of DE in patients who underwent p-PCI can be predicted using a simple 4-variables model based on angiographic features. PMID- 26260397 TI - Six-Year Prognostic Value of Microvascular Obstruction After Reperfused ST Elevation Myocardial Infarction as Assessed by Contrast-Enhanced Cardiovascular Magnetic Resonance. AB - Although recent studies showed the prognostic value of cardiac magnetic resonance (CMR) parameters especially microvascular obstruction (MO) after reperfused ST elevation myocardial infarction (STEMI), a study assessing their prognostic significance for long-term follow-up is missing so far. The objective of this study was to determine the prognostic impact of MO on long-term prognosis after reperfused first STEMI in a setting allocating CMR-assessed parameters to hard clinical events only. In 249 patients, CMR was performed after reperfused STEMI, and hereby, left ventricular ejection fraction (LVEF), infarct size (IS), and the amount of MO were quantified. Follow-up (median 6.0 years) was obtained regarding occurrence of major adverse cardiac events (MACE). MACE occurred more often in patients showing presence of MO (MO vs no MO: n = 61 [54%] vs n = 12 [9%], p <0.0001). By multivariate analysis, the extent of MO remained the strongest predictor (p <0.001) for occurrence of MACE and provided incremental prognostic value over clinical variables and LVEF (p = 0.028, c-index increase from 0.723 to 0.817). In conclusion, CMR-assessed MO proves predictive for assessment of 6-year prognosis in patients after reperfused first STEMI and provides incremental prognostic information over clinical variables and LVEF in a setting based on hard end points. PMID- 26260399 TI - Promoting Fruit and Vegetables in Young Children: What Advice Can Pediatricians Give to Parents? PMID- 26260398 TI - Association of Chronic Kidney Disease With Chronotropic Incompetence in Heart Failure With Preserved Ejection Fraction. AB - Chronotropic incompetence (CI) is common in heart failure with preserved ejection fraction (HFpEF) and may be a key reason underlying exercise intolerance in these patients. However, the determinants of CI in HFpEF are unknown. We prospectively studied 157 patients with consecutive HFpEF who underwent cardiopulmonary exercise testing and defined CI according to specific thresholds of the percent heart rate reserve (%HRR). CI was diagnosed as present if %HRR <80 if not taking a beta blocker and <62 if taking beta blockers. Participants who achieved inadequate exercise effort (respiratory exchange ratio <=1.05) on cardiopulmonary exercise testing were excluded. Multivariable-adjusted logistic regression was used to determine the factors associated with CI. Of the 157 participants, 108 (69%) achieved a respiratory exchange ratio >1.05 and were included in the final analysis. Of these 108 participants, 70% were women, 62% were taking beta blockers, and 38% had chronic kidney disease. Most patients with HFpEF met criteria for CI (81 of 108; 75%). Lower estimated glomerular filtration rate (GFR), higher B-type natriuretic peptide, and higher pulmonary artery systolic pressure were each associated with CI. A 1-SD decrease in GFR was independently associated with CI after multivariable adjustment (adjusted odds ratio 2.2, 95% confidence interval 1.1 to 4.4, p = 0.02). The association between reduced GFR and CI persisted when considering a variety of measures of chronotropic response. In conclusion, reduced GFR is the major clinical correlate of CI in patients with HFpEF, and further study of the relation between chronic kidney disease and CI may provide insight into the pathophysiology of CI in HFpEF. PMID- 26260400 TI - Major Themes in the Personal Statements of Pediatric Resident Applicants. PMID- 26260401 TI - Facial Pain in a Child With Attention Deficit Hyperactivity Disorder. PMID- 26260402 TI - The Risk of Musculoskeletal Adverse Events With Fluoroquinolones in Children: What Is the Verdict Now? PMID- 26260403 TI - TLR9 regulates adipose tissue inflammation and obesity-related metabolic disorders. AB - OBJECTIVE: Recent studies have revealed a link between Toll-like receptor (TLR) signaling and the adipose tissue inflammation associated with obesity. Although TLR9 is known to play an important role in inflammation and innate immunity, its role in mediating adipose tissue inflammation has not yet been investigated. Thus, the objective of this study was to determine the role of TLR9 in regulating immune cells in visceral adipose tissue and maintaining the metabolic homeostasis. METHODS: Wild-type and TLR9-deficient mice were fed with a high-fat diet, and the body weight gain, glucose tolerance, insulin sensitivity, and adipose tissue inflammation were examined. RESULTS: TLR9-deficient mice gained significantly more weight and body fat under a high-fat diet than wild-type mice and exhibited more severe glucose intolerance and insulin resistance. We also found a dramatic increase of M1 macrophages as well as TH 1 cells in the adipose tissue of TLR9-deficient mice compared to wild-type mice. Furthermore, the levels of various proinflammatory cytokines and chemokines were higher in TLR9-deficient mice. CONCLUSIONS: TLR9 signaling is involved in regulating adipose tissue inflammation and controlling obesity and the metabolic syndrome. PMID- 26260404 TI - Improving mental and physical health outcomes in general healthcare settings: a Gedenkschrift in honor of Wayne Katon, MD (1950-2015). AB - This special article pays tribute to Wayne Katon, MD (1950-2015) with a Gedenkschrift, or review, of his prolific academic career. Abstracts of all of Dr. Katon's Medline citations were reviewed to develop a narrative of his seminal epidemiological and interventional research findings. Specifically, we describe: (a) how Dr. Katon's clinical work and observational epidemiology and health services research informed and guided interventional studies; (b) the evolution of multidisciplinary interventional trials from primary care-based psychiatric consultation to primary care-based collaborative care for depression to multicondition collaborative care; and (c) how Dr. Katon's research has informed the work of other leading researchers in the field of psychosomatic medicine and helped develop a new generation of researchers at the interface of psychiatry and primary care. For more than three decades, Dr. Katon led a multidisciplinary research team that conducted seminal epidemiological studies and randomized trials and that influenced the thinking and research in the field of psychiatry in a number of areas: (a) the importance and impact of mental disorders presenting in primary care settings and (b) the organization of effective multidisciplinary care for primary care patients with common mental disorders and comorbid medical conditions. Dr. Katon's work revolutionized the care of psychiatric illnesses in primary care and other medical care settings to the benefit of countless patients worldwide. PMID- 26260405 TI - Continuous flow synthesis of a carbon-based molecular cage macrocycle via a three fold homocoupling reaction. AB - The facile synthesis of the cage molecule (C110H56Br2) via a remarkable three fold homo-coupling macrocyclization reaction using continuous flow methodology is reported. Synthesis via continuous flow chemistry improves the residence time, safety, and environmental profile of this synthetically challenging reaction. Further, the new cage possesses halogen atoms at its apex that serve to expand the potential reaction space of these intrinsically porous, all carbon-carbon bonded molecular cage molecules. PMID- 26260406 TI - Periconceptional folic acid fortification for the risk of gestational hypertension and pre-eclampsia: a meta-analysis of prospective studies. AB - Published literatures report controversial results about the association of folic acid-containing multivitamins with gestational hypertension and pre-eclampsia. A comprehensive search was performed to identify related prospective studies to assess the effect of folic acid fortification on gestational hypertension and pre eclampsia. The Q test and I(2) statistic were used to examine between-study heterogeneity. Fixed or random effects models were selected based on study heterogeneity. A funnel plot and modified Egger linear regression test were used to estimate publication bias. Eleven studies conformed to the criteria. Pooled results indicated that folic acid fortification alone was not associated with the occurrence of gestational hypertension [relative risk (RR) = 1.03, 95% confidence interval (CI): 0.98-1.09, P = 0.267] and pre-eclampsia (RR = 0.99, 95% CI: 0.90 1.08, P = 0.738). However, supplementation of multivitamins containing folic acid could prevent gestational hypertension (RR = 0.57, 95% CI: 0.43-0.76, P < 0.001) and pre-eclampsia (RR = 0.64, 95% CI: 0.48-0.84, P = 0.001). The difference between folic acid fortification alone and multivitamins containing folic acid was significant. This meta-analysis suggests that periconceptional multivitamin supplementation with appropriate dose, not folic acid alone, is an appropriate recommendation for pregnant women. The effect should be further confirmed by conducting large-scale randomised controlled trials. PMID- 26260407 TI - Susceptibility versus resistance in alveolar echinococcosis (larval infection with Echinococcus multilocularis). AB - Epidemiological studies have demonstrated that the majority of human individuals exposed to infection with Echinococcus spp. eggs exhibit resistance to disease as shown by either seroconversion to parasite--specific antigens, and/or the presence of 'dying out' or 'aborted' metacestodes, not including hereby those individuals who putatively got infected but did not seroconvert and who subsequently allowed no development of the pathogen. For those individuals where infection leads to disease, the developing parasite is partially controlled by host immunity. In infected humans, the type of immune response developed by the host accounts for the subsequent trichotomy concerning the parasite development: (i) seroconversion proving infection, but lack of any hepatic lesion indicating the failure of the parasite to establish and further develop within the liver; or resistance as shown by the presence of fully calcified lesions; (ii) controlled susceptibility as found in the "conventional" alveolar echinococcosis (AE) patients who experience clinical signs and symptoms approximately 5-15 years after infection, and (iii) uncontrolled hyperproliferation of the metacestode due to an impaired immune response (AIDS or other immunodeficiencies). Immunomodulation of host immunity toward anergy seems to be triggered by parasite metabolites. Beside immunomodulating IL-10, TGFbeta-driven regulatory T cells have been shown to play a crucial role in the parasite-modulated progressive course of AE. A novel CD4+CD25+ Treg effector molecule FGL2 recently yielded new insight into the tolerance process in Echinococcus multilocularis infection. PMID- 26260408 TI - Taxonomy, phylogeny and molecular epidemiology of Echinococcus multilocularis: From fundamental knowledge to health ecology. AB - Alveolar echinococcosis, caused by the tapeworm Echinococcus multilocularis, is one of the most severe parasitic diseases in humans and represents one of the 17 neglected diseases prioritised by the World Health Organisation (WHO) in 2012. Considering the major medical and veterinary importance of this parasite, the phylogeny of the genus Echinococcus is of considerable importance; yet, despite numerous efforts with both mitochondrial and nuclear data, it has remained unresolved. The genus is clearly complex, and this is one of the reasons for the incomplete understanding of its taxonomy. Although taxonomic studies have recognised E. multilocularis as a separate entity from the Echinococcus granulosus complex and other members of the genus, it would be premature to draw firm conclusions about the taxonomy of the genus before the phylogeny of the whole genus is fully resolved. The recent sequencing of E. multilocularis and E. granulosus genomes opens new possibilities for performing in-depth phylogenetic analyses. In addition, whole genome data provide the possibility of inferring phylogenies based on a large number of functional genes, i.e. genes that trace the evolutionary history of adaptation in E. multilocularis and other members of the genus. Moreover, genomic data open new avenues for studying the molecular epidemiology of E. multilocularis: genotyping studies with larger panels of genetic markers allow the genetic diversity and spatial dynamics of parasites to be evaluated with greater precision. There is an urgent need for international coordination of genotyping of E. multilocularis isolates from animals and human patients. This could be fundamental for a better understanding of the transmission of alveolar echinococcosis and for designing efficient healthcare strategies. PMID- 26260409 TI - A large-scale study of the Trichinella genus in the golden jackal (Canis aureus) population in Serbia. AB - Over the last decades the golden jackal (Canis aureus) has significantly expanded its range throughout Southeast and Central Europe, and the Balkan Peninsula is considered to be a core area of the species distribution in this part of the range. Due to its increasing number, ability of long distance movement through a wide range of landscapes and opportunistic feeding habits, the golden jackal may represent an important reservoir and transmitter of a variety of zoonotic agents, including parasites. The Balkans, Serbia included, remain an endemic area for various zoonotic parasites including Trichinella spp. Trichinella has recently been recorded in jackals in Serbia, which prompted us to carry out a large-scale survey of its prevalence, distribution and species identification in this host. In cooperation with local hunters, carcasses of a total of 738 legally hunted golden jackals were collected at 24 localities over an 11-year period (2003 2013). Analysis of tongue base tissue revealed Trichinella larvae in 122, indicating a prevalence of infection of 16.5%. No difference in the prevalence of infection was found between genders [16.2% in males and 16.9% in females (chi(2)=0.05, p=0.821)], or among the study years (G=7.22, p=0.705). Trichinella larvae were found in 13 out of the 24 examined localities. Molecular identification was performed for 90 isolates, and 64 (71.1%) larvae were identified as Trichinella spiralis and 25 (27.9%) as Trichinella britovi. Mixed infection (T. spiralis and T. britovi) was recorded in a single case. Although T. spiralis was more prevalent, T. britovi had a wider distribution, and was the only recorded species in jackal populations from the mountainous region of eastern Serbia. On the other hand, T. spiralis was dominant in jackals in the lowlands of central and northern Serbia, where domestic pigs are mostly reared. These results show that the golden jackal is involved in both the domestic and sylvatic cycle, and that it has emerged as a major host species in the sylvatic cycle of the Trichinella genus. Therefore, continued monitoring of Trichinella infection in golden jackals in Serbia and the whole of the Balkans is recommended in order to control transmission of this parasite to humans and domestic animals. PMID- 26260410 TI - The reviewers of Actas Urologicas Espanolas. A privilege for our Urology. PMID- 26260411 TI - Alcohol- and drug-related absenteeism: a costly problem. AB - OBJECTIVE: Absenteeism related to alcohol and other drug (AOD) use can place a substantial burden on businesses and society. This study estimated the cost of AOD-related absenteeism in Australia using a nationally representative dataset. METHODS: A secondary analysis of the 2013 National Drug Strategy Household Survey (n=12,196) was undertaken. Two measures of AOD-related absenteeism were used: participants' self-reported absence due to AOD use (M1); and the mean difference in absence due to any illness/injury for AOD users compared to abstainers (M2). Both figures were multiplied by $267.70 (average day's wage in 2013 plus 20% on costs) to estimate associated costs. RESULTS: M1 resulted in an estimation of 2.5 million days lost annually due to AOD use, at a cost of more than $680 million. M2 resulted in an estimation of almost 11.5 million days lost, at a cost of $3 billion. CONCLUSIONS: AOD-related absenteeism represents a significant and preventable impost upon Australian businesses. IMPLICATIONS: Workplaces should implement evidence-based interventions to promote healthy employee behaviour and reduce AOD-related absenteeism. PMID- 26260412 TI - Mechanisms and in vitro effects of cepharanthine hydrochloride: Classification analysis of the drug-induced differentially-expressed genes of human nasopharyngeal carcinoma cells. AB - Nasopharyngeal carcinoma (NPC) is the most commonly diagnosed head and neck malignancy and is prevalent worldwide. Previous studies have demonstrated the antitumor properties of cepharanthine hydrochloride (CH) in several human cancer cells. However, the action of CH in NPC cells has yet to be determined. In the present study, we investigated the effects of CH in human NPC cell lines including CNE-1 and CNE-2 on cell growth and apoptosis in vitro. Using MTT and ATP-tumor chemosensitivity assays it was found that CH inhibited cell viability. Additionally, flow cytometric and analysis electron microscopy revealed the inhibition of cell cycle progression and reduction of apoptosis, respectively, in human NPC cell lines including CNE-1 and CNE-2 in vitro. To identify the potential action mechanisms of CH, the cDNA microarray analysis results were confirmed by quantitative PCR analysis using a number of genes, including CDKN1A/P21, NR4A1/TR3 and DAXX. In total, 138 upregulated and 63 downregulated genes in CNE-2 cells were treated with CH. According to their biological function, the genes were classified as: i) cell cycle-related genes; ii) DNA repair-related genes; iii) apoptosis-related genes and iv) nuclear factor-kappaB (NF-kappaB) transcription factors signal pathways. The results of the present study showed that CH is a potential therapeutic agent against human NPC, and provide rational explanations and a scientific basis for the study of the development of CH in the treatment of NPC. PMID- 26260413 TI - Fish oil and krill oil differentially modify the liver and brain lipidome when fed to mice. AB - BACKGROUND: Marine food is an important source of omega-3 fatty acids with beneficial health effects. Oils from marine organisms have different fatty acid composition and differ in their molecular composition. Fish oil (FO) has a high content of eicosapentaenoic and docosahexaenoic acids mainly esterified to triacylglycerols, while in krill oil (KO) these fatty acids are mainly esterified to phospholipids. The aim was to study the effects of these oils on the lipid content and fatty acid distribution in the various lipid classes in liver and brain of mice. METHODS: Mice were fed either a high-fat diet (HF), a HF diet supplemented with FO or with KO (n = 6). After six weeks of feeding, liver and brain lipid extracts were analysed using a shotgun and TAG lipidomics approach. Student t-test was performed after log-transformation to compare differences between study groups. RESULTS: Six weeks of feeding resulted in significant changes in the relative abundance of many lipid classes compared to control mice. In both FO and KO fed mice, the triacylglycerol content in the liver was more than doubled. The fatty acid distribution was affected by the oils in both liver and brain with a decrease in the abundance of 18:2 and 20:4, and an increase in 20:5 and 22:6 in both study groups. 18:2 decreased in all lipid classes in the FO group but with only minor changes in the KO group. Differences between the feeding groups were particularly evident in some of the minor lipid classes that are associated with inflammation and insulin resistance. Ceramides and diacylglycerols were decreased and cholesteryl esters increased in the liver of the KO group, while plasmalogens were decreased in the FO group. In the brain, diacylglycerols were decreased, more by KO than FO, while ceramides and lactosylceramides were increased, more by FO than KO. CONCLUSION: The changes in the hepatic sphingolipids and 20:4 fatty acid levels were greater in the KO compared to the FO fed mice, and are consistent with a hypothesis that krill oil will have a stronger anti-inflammatory action and enhances insulin sensitivity more potently than fish oil. PMID- 26260414 TI - Synthesis, Biological, and Computational Evaluation of Novel 1,3,5-Substituted Indolin-2-one Derivatives as Inhibitors of Src Tyrosine Kinase. AB - Several substituted indolin-2-one derivatives were synthesized and evaluated for their activities against Src kinase. Several compounds showed activity against Src, with IC50 values in the low micromolar range. Among them, compound 2f showed the most significant activity with an IC50 value of 1.02 MUM. Molecular docking studies have been performed for evaluation of the binding modes of compound 2f into the Src active site. The docking structure of compound 2f disclosed that the indole NH forms a hydrogen bond with the carbonyl of Met341. These results suggest that our novel compound 2f is a promising compound for the further development of indole-based drugs targeting Src kinase. PMID- 26260415 TI - Copper-catalyzed aerobic autoxidation of N-hydroxycarbamates probed by mass spectrometry. AB - We present herein a mechanistic investigation by nanoelectrospray ionization mass spectrometry of copper-catalyzed aerobic oxidative processes involved in the N nitrosocarbonyl aldol reaction of N-hydroxycarbamates. Protonated amine and copper as charge-tags aided the detection of reaction intermediates, which verified the enamine mechanism together with a competing enol process. Our experimental results reveal that the copper-catalyzed aerobic oxidation of N hydroxycarbamates may proceed through an autoxidation catalytic mechanism in which a CbzNHO(.) radical abstracts a hydrogen from the bound N-hydroxycarbamate to release the nitroso intermediate through a bimolecular hydrogen-atom transfer. In this process, the chiral diamine also works as a ligand for copper to facilitate the aerobic oxidative step. The dual role of the chiral vicinal diamine as both an aminocatalyst and a bidentate ligand was finally uncovered. PMID- 26260416 TI - Genetic structure and relationships of 16 Asian and European cattle populations using DigiTag2 assay. AB - In this study, we genotyped 117 autosomal single nucleotide polymorphisms using a DigiTag2 assay to assess the genetic diversity, structure and relationships of 16 Eurasian cattle populations, including nine cattle breeds and seven native cattle. Phylogenetic and principal component analyses showed that Bos taurus and Bos indicus populations were clearly distinguished, whereas Japanese Shorthorn and Japanese Polled clustered with European populations. Furthermore, STRUCTURE analysis demonstrated the distinct separation between Bos taurus and Bos indicus (K=2), and between European and Asian populations (K=3). In addition, Japanese Holstein exhibited an admixture pattern with Asian and European cattle (K=3-5). Mongolian (K=13-16) and Japanese Black (K=14-16) populations exhibited admixture patterns with different ancestries. Bos indicus populations exhibited a uniform genetic structure at K=2-11, thereby suggesting that there are close genetic relationships among Bos indicus populations. However, the Bhutan and Bangladesh populations formed a cluster distinct from the other Bos indicus populations at K=12-16. In conclusion, our study could sufficiently explain the genetic construction of Asian cattle populations, including: (i) the close genetic relationships among Bos indicus populations; (ii) the genetic influences of European breeds on Japanese breeds; (iii) the genetic admixture in Japanese Holstein, Mongolian and Japanese Black cattle; and (iv) the genetic subpopulations in Southeast Asia. PMID- 26260418 TI - Clever surgeons and challenging study endpoints. PMID- 26260417 TI - Electrospun PLA/MWCNTs composite nanofibers for combined chemo- and photothermal therapy. AB - Carbon nanotubes are effective thermal generators by absorbing near-infrared radiation (NIR). In this study, multiwalled carbon nanotubes (MWCNTs) and doxorubicin (DOX) were successfully electrospun into the poly-l-lactic acid (PLLA) nanofibers. It is confirmed that NIR radiation could not only initiate burst release of DOX from the fibers due to the relatively low glass transition temperature (Tg) of PLLA, but also significantly increase the temperature of fibers-covering tumor site. The multifunctional fibers showed increased cytotoxicity both in vitro and in vivo by the combination of photothermal induced hyperthermia and chemotherapy with DOX. This drug delivery system could be very useful and convenient in future clinical applications for localized cancer therapy. STATEMENT OF SIGNIFICANCE: Combination of chemo- and photothermal therapy has been widely researched owing to its enhanced cancer treatment efficacy. In this study, chemotherapy and photothermal therapy were integrated into one single system using electrospun DOX/MWCNTs loaded PLLA nanofiber mats and the anti-cancer efficacy of the fibers was studied in vivo for the first time. The effective NIR irradiation control showed a typical switch on/off effect on the release behavior of drug. As local delivery system, the fibers maximize the drug concentration in tumor and keep the MWCNTs in the surroundings of tumor, thus allowing a repeated localized heating. The high porosity of nanofibers is easy for cell binding, which may present an attractive alternative for local hyperthermia treatment of easily metastasizing tumors. PMID- 26260419 TI - Hot topic of cancer survivorship and the 'seven deadly sins'. PMID- 26260420 TI - Robotic partial nephrectomy: the treatment of choice for minimally invasive nephron-sparing surgery. PMID- 26260421 TI - Do 'whale noises' help in the diagnosis of Fowler's syndrome? PMID- 26260422 TI - Changes in temporomandibular joint morphology in class II patients treated with fixed mandibular repositioning and evaluated through 3D imaging: a systematic review. AB - To estimate the effects of skeletal class II malocclusion treatment using fixed mandibular repositioning appliances on the position and morphology of the temporomandibular joint (TMJ). Two independent reviewers performed comprehensive electronic searches of MEDLINE, EMBASE, EBM reviews and Scopus (until May 5, 2015). The references of the identified articles were also manually searched. All studies investigating morphological changes of the TMJ articular disc, condyle and glenoid fossa with 3D imaging following non-surgical fixed mandibular repositioning appliances in growing individuals with class II malocclusions were included in the analysis. Of the 269 articles initially reviewed, only 12 articles used magnetic resonance imaging and two articles used computed tomography (CT) or cone-beam CT images. Treatment effect on condyle and glenoid fossa was discussed in eight articles. Treatment effect on TMJ articular disc position and morphology was discussed in seven articles. All articles showed a high risk of bias due to deficient methodology: inadequate consideration of confounding variables, blinding of image assessment, selection or absence of control group and outcome measurement. Reported changes in osseous remodelling, condylar and disc position were contradictory. The selected articles failed to establish conclusive evidence of the exact nature of TMJ tissue response to fixed mandibular repositioning appliances. PMID- 26260423 TI - Antecedent blood pressure as a predictor of cardiovascular disease. AB - Elevated blood pressure (BP) is associated with greater risk of cardiovascular disease (CVD), and evidence suggests that prior BP levels may be at least as important as current BP in prediction models. We analyzed the determinants of CVD risk in Offspring Framingham Heart Study participants (n = 3344). The baseline Cox model included the traditional risk factors and current systolic BP to predict 20-year risk of CVD (643 events). Current systolic BP was significant, and the associated hazard ratio was 1.09 for 10 mm Hg (confidence interval [CI] 95%: 1.04-1.15). A second model used the traditional risk factors plus antecedent BP (hazard ratio [HR] = 1.19; CI 95%: 1.10-1.24). In a third model that included traditional risk factors and both current and antecedent BP, the antecedent BP was significant (HR = 1.18; CI 95%: 1.08-1.23), but the current BP was not statistically significant (HR = 1.01; CI 95%: 0.97-1.09). Antecedent BP showed a significantly stronger effect on risk of CVD than current BP. PMID- 26260424 TI - Ambulatory Arterial Stiffness Index and circadian blood pressure variability. AB - The manner in which the circulation accommodates each heartbeat may underlie blood pressure (BP) variability. We used the Ambulatory Arterial Stiffness Index (AASI), which reflects this ventricular-vascular interaction, in untreated individuals with prehypertension and Stage 1 hypertension to evaluate two different measures of BP variability using the brachial pulse pressure (PP) obtained over 24 hours. We enrolled 64 untreated adults with systolic BP between 130-159 mm Hg and diastolic values of <100 mm Hg who underwent 24-hour ambulatory BP monitoring with calculation of 24-hour AASIs. Variability in brachial PP was determined using the standard deviation of the measurements over 24 hours and the average real variability. The 24-hour AASI correlated with both measures of 24 hour PP variability (P < .001 for both). Subdividing the 24-hour stiffness index into daytime and nighttime components showed modest differences in their relationship to PP variability, with the daytime being significantly different from 24-hour AASI and the standard deviation of the brachial PP consistently having a higher correlation to the AASI when compared with the average real variability. These observations may be useful to understand differences in variability measures of BP measurements, such as PP, to measures like the AASI as reported in longitudinal studies. PMID- 26260425 TI - Is there a bend in the upward trend of high blood pressure in childhood?: A commentary on prevalence of and trends in dyslipidemia and blood pressure among US children and adolescents, 1999-2012. PMID- 26260428 TI - High resolution whole brain diffusion imaging at 7T for the Human Connectome Project. AB - Mapping structural connectivity in healthy adults for the Human Connectome Project (HCP) benefits from high quality, high resolution, multiband (MB) accelerated whole brain diffusion MRI (dMRI). Acquiring such data at ultrahigh fields (7T and above) can improve intrinsic signal-to-noise ratio (SNR), but suffers from shorter T2 and T2(*) relaxation times, increased B1(+) inhomogeneity (resulting in signal loss in cerebellar and temporal lobe regions), and increased power deposition (i.e. specific absorption rate (SAR)), thereby limiting our ability to reduce the repetition time (TR). Here, we present recent developments and optimizations in 7T image acquisitions for the HCP that allow us to efficiently obtain high quality, high resolution whole brain in-vivo dMRI data at 7T. These data show spatial details typically seen only in ex-vivo studies and complement already very high quality 3T HCP data in the same subjects. The advances are the result of intensive pilot studies aimed at mitigating the limitations of dMRI at 7T. The data quality and methods described here are representative of the datasets that will be made freely available to the community in 2015. PMID- 26260430 TI - Neuroplasticity and MRI: A perfect match. AB - Numerous studies have illustrated the benefits of physical workout and cognitive exercise on brain function and structure and, more importantly, on decelerating cognitive decline in old age and promoting functional rehabilitation following injury. Despite these behavioral observations, the exact mechanisms underlying these neuroplastic phenomena remain obscure. This gap illustrates the need for carefully designed in-depth studies using valid models and translational tools which allow to uncover the observed events up to the molecular level. We promote the use of in vivo magnetic resonance imaging (MRI) because it is a powerful translational imaging technique able to extract functional, structural, and biochemical information from the entire brain. Advanced processing techniques allow performing voxel-based analyses which are capable of detecting novel loci implicated in specific neuroplastic events beyond traditional regions-of-interest analyses. In addition, its non-invasive character sets it as currently the best global imaging tool for performing dynamic longitudinal studies on the same living subject, allowing thus exploring the effects of experience, training, treatment etc. in parallel to additional measures such as age, cognitive performance scores, hormone levels, and many others. The aim of this review is (i) to introduce how different animal models contributed to extend the knowledge on neuroplasticity in both health and disease, over different life stages and upon various experiences, and (ii) to illustrate how specific MRI techniques can be applied successfully to inform on the fundamental mechanisms underlying experience-dependent or activity-induced neuroplasticity including cognitive processes. PMID- 26260429 TI - Brain extraction in pediatric ADC maps, toward characterizing neuro-development in multi-platform and multi-institution clinical images. AB - Apparent Diffusion Coefficient (ADC) maps can be used to characterize myelination and to detect abnormalities in the developing brain. However, given the normal variation in regional ADC with myelination, detection of abnormalities is difficult when based on visual assessment. Quantitative and automated analysis of pediatric ADC maps is thus desired but requires accurate brain extraction as the first step. Currently, most existing brain extraction methods are optimized for structural T1-weighted MR images of fully myelinated brains. Due to differences in age and image contrast, these approaches do not translate well to pediatric ADC maps. To address this problem, we present a multi-atlas brain extraction framework that has 1) specificity: designed and optimized specifically for pediatric ADC maps; 2) generality: applicable to multi-platform and multi institution data, and to subjects at various neuro-developmental stages across the first 6 years of life; 3) accuracy: highly accurate compared to expert annotations; and 4) consistency: consistently accurate regardless of sources of data and ages of subjects. We show how we achieve these goals, via optimizing major components in a multi-atlas brain extraction framework, and via developing and evaluating new criteria for its atlas ranking component. Moreover, we demonstrate that these goals can be achieved with a fixed set of atlases and a fixed set of parameters, which opens doors for our optimized framework to be used in large-scale and multi-institution neuro-developmental and clinical studies. In a pilot study, we use this framework in a dataset containing scanner-generated ADC maps from 308 pediatric patients collected during the course of routine clinical care. Our framework leads to successful quantifications of the changes in whole-brain volumes and mean ADC values across the first 6 years of life. PMID- 26260431 TI - Aberrant mesolimbic dopamine-opiate interaction in obesity. AB - Dopamine and opioid neurotransmitter systems share many functions such as regulation of reward and pleasure. MU-Opioid receptors (MOR) modulate the mesolimbic dopamine system in ventral tegmental area and striatum, key areas implicated in reward. We hypothesized that dopamine and opioid receptor availabilities correlate in vivo and that this correlation is altered in obesity, a disease with altered reward processing. Twenty lean females (mean BMI 22) and 25 non-binge eating morbidly obese females (mean BMI 41) underwent two positron emission tomography scans with [(11)C]carfentanil and [(11)C]raclopride to measure the MOR and dopamine D2 receptor (DRD2) availability, respectively. In lean subjects, the MOR and DRD2 availabilities were positively associated in the ventral striatum (r=0.62, p=0.003) and dorsal caudate nucleus (r=0.62, p=0.004). Moreover, DRD2 availability in the ventral striatum was associated with MOR availability in other regions of the reward circuitry, particularly in the ventral tegmental area. In morbidly obese subjects, this receptor interaction was significantly weaker in ventral striatum but unaltered in the caudate nucleus. Finally, the association between DRD2 availability in the ventral striatum and MOR availability in the ventral tegmental area was abolished in the morbidly obese. The study demonstrates a link between DRD2 and MOR availabilities in living human brain. This interaction is selectively disrupted in mesolimbic dopamine system in morbid obesity. We propose that interaction between the dopamine and opioid systems is a prerequisite for normal reward processing and that disrupted cross-talk may underlie altered reward processing in obesity. PMID- 26260432 TI - Changes to food intake and nutrition of female red-tailed phascogales (Phascogale calura) during late lactation. AB - Reproduction and especially lactation are nutritionally costly for mammals. Maternal access to adequate and optimal nutrients is essential for fecundity, survival of offspring, and offspring growth rates. In eutherian species energy requirements during lactation can be heavily dependent on litter size and the body mass of the female. In marsupials litter size does not appear to affect nutritional requirements during lactation; however, studies of marsupial nutritional requirements during lactation are rare. Marsupials are distinct from eutherians as they give birth to young at a much more underdeveloped state and the majority of their investment into the growth of their offspring occurs postnatally. Nutritional requirements of adult female red-tailed phascogales (Phascogale calura) were measured to determine the differences between those lactating and not lactating. On average females that were lactating had maintenance energy requirements of 1728 +/- 195 kJ kg(-0.75) d(-1), double that of non-lactating animals. There was no significant correlation between energy requirements and litter size among lactating female phascogales. Apparent absorption of macronutrients did not differ between lactating and non-lactating individuals. The study has shown that food needs to be increased by at least double during late lactation. Litter size appears to have no influence on maternal nutrient requirements when food is available ad libitum and offspring in smaller litters grow faster than those in larger litters. PMID- 26260433 TI - Climbing experience in glass eels: A cognitive task or a matter of physical capacities? AB - The European eel is a panmictic species, whose decline has been recorded since the last 30 years. Among human-induced environmental factors of decline, the impact of water dams during species migration is questioned. Indeed, water impoundments can be a severe obstacle for young eels trying to reach the upstream freshwater zones, even if they are equipped with fish-friendly passes. The passage by such devices could be an important event shaping the outcome of the future life and life history traits of eels. We studied what phenotypic traits were associated with the event of experience of passage by water obstacles. We analyzed specific enzyme activities and/or gene transcription levels in the muscle and brain to test whether the obstacle passage is rather a physical or cognitive task. We found that after a long period of maintenance under homogenous conditions, transcription levels of several genes linked to synaptic plasticity, neurogenesis and thyroid activity differed among the field-experience groups. In contrast, muscle gene transcription levels or enzymatic activities did not show any differences among fish groups. We suggest that cognitive processes such as learning and memory acquisition rather than swimming-related metabolic capacities are involved in passage of water obstacles by young eels. PMID- 26260434 TI - Sex differences in body fluid homeostasis: Sex chromosome complement influences on bradycardic baroreflex response and sodium depletion induced neural activity. AB - Clinical and basic findings indicate that angiotensin II (ANG II) differentially modulates hydroelectrolyte and cardiovascular responses in male and female. But are only the activational and organizational hormonal effects to blame for such differences? Males and females not only differ in their sex (males are born with testes and females with ovaries) but also carry different sex chromosome complements and are thus influenced throughout life by different genomes. In this review, we discuss our recent studies in order to evaluate whether sex chromosome complement is in part responsible for gender differences previously observed in ANG II bradycardic-baroreflex response and sodium depletion-induced sodium appetite and neural activity. To test the hypothesis that XX or XY contributes to the dimorphic ANG II bradycardic-baroreflex response, we used the four core genotype mouse model, in which the effects of gonadal sex (testes or ovaries) and sex chromosome complement (XX or XY) are dissociated. The results indicate that ANG II bradycardic-baroreflex sexual dimorphic response may be ascribed to differences in sex chromosomes, indicating an XX-sex chromosome complement facilitatory bradycardic-baroreflex control of heart rate. Furthermore, we evaluated whether genetic differences within the sex chromosome complement may differentially modulate the known sexually dimorphic sodium appetite as well as basal or induced brain activity due to physiological stimulation of the renin angiotensin system by furosemide and low-sodium treatment. Our studies demonstrate an organizational hormonal effect on sexually dimorphic induced sodium intake in mice, while at the brain level (subfornical organ and area postrema) we showed a sex chromosome complement effect in sodium-depleted mice, suggesting a sex chromosome gene participation in the modulation of neural pathways underlying regulatory response to renin-angiotensin stimulation. PMID- 26260435 TI - Impact of obesity on autonomic modulation, heart rate and blood pressure in obese young people. AB - INTRODUCTION: Obesity can be understood as a comorbidity of increasing systemic impact, including a deficit in the autonomic nervous system. OBJECTIVE: To analyze cardiac autonomic behavior and hemodynamic parameters in obese young people. METHODS: 92 individuals (20.58+/-1.48 years) were evaluated, divided into two groups: obese and eutrophic. Heart rate (HR) was captured for 30 min in the supine position whilst breathing spontaneously. Blood pressure (BP) values were obtained prior to performance of the protocol. For the autonomic analysis, 1000 beats were used for the calculation of heart rate variability indices in the time (Mean RR, SDNN and RMSSD) and frequency (LF, HF and LF/HF) domains, in addition to the Poincare plot (SD1, SD2, SD1/SD2 and qualitative visual analysis). RESULTS: The obese group presented higher baseline BP and HR values compared to the eutrophic. Regarding autonomic modulation a significant decrease was observed in the RMSSD; SD1, HFms and HFnu indices in the obese group, indicating a decrease in vagal activity and reduced SDNN and SD2 rates, with statistical significance for the former, suggesting a reduction in overall variability. The high value of the LFnu index and decrease in Mean RR in the obese group pointed to relative sympathetic predominance in these individuals. The visual analysis of the Poincare plot showed less dispersion of the points in the obese group. CONCLUSION: The obese group presented higher BP and HR values at rest and autonomic impairment, characterized by a reduction in parasympathetic activity and relative predominance of sympathetic activity. PMID- 26260436 TI - In vitro opioid receptor affinity and in vivo behavioral studies of Nelumbo nucifera flower. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Nelumbo nucifera Geartn., known as sacred lotus, has been used traditionally in South East Asia as a traditional medicine for various CNS disorders including stress, fever, depression, insomnia, and cognitive conditions. AIM OF THE STUDY: To investigate the in vitro cannabinoid and opioid receptor binding affinities, and in vivo behavioral actions of Nelumbo flower extracts and to isolate the potential compounds to treat CNS associated disorders. MATERIALS AND METHODS: The white and pink flowers of N. nucifera were extracted with 95% EtOH, followed by acid-base partitioning using CHCl3 to give acidic and basic partitions. These partitions were subjected to Centrifugal Preparative TLC (CPTLC) to yield benzyltetrahydroisoquinoline (BTIQ) alkaloids and long chain fatty acids, identified by physical and spectroscopic methods. In addition, EtOH extracts and partitions were analyzed for chemical markers by UHPLC/MS and GC/MS. In vitro neuropharmacological effects were evaluated by cannabinoid (CB1 and CB2) and opioid [delta (delta), kappa (K), and mu (u)] competitive radioligand binding and GTPgammaS functional assays. The in vivo behavioral effect was studied through the use of the mouse tetrad assay at 10, 30, 75 and 100mg/kg/ip doses that revealed the effect on locomotion, catalepsy, body temperature, and nociception of acidic and basic CHCl3 partitions, fractions, and compounds. RESULTS: Three aporphines, nuciferine (1), N-nor nuciferine (2), asimilobine (3), and five BTIQs, armepavine (4), O methylcoclaurine (5), N-methylcoclaurine (6), coclaurine (7), neferine (10), and a mixture of linoleic and palmitic acids (LA and PA), were identified and evaluated for cannabinoid and opioid receptor displacement activities. Compounds 5-7 showed binding affinities for the K opioid receptor with equilibrium dissociation constant (Ki) values of 3.5 +/- 0.3, 0.9 +/- 0.1, 2.2 +/- 0.2 MUM, respectively. Compound 10 displayed affinities for delta-and u- opioid receptors with Ki values of 0.7 +/- 0.1 and 1.8 +/- 0.2 MUM, respectively, and was determined to be a weak delta agonist by GTPgammaS functional assay. The mixture of LA and PA (1:1) showed an affinity for delta opioid receptor with a Ki value of 9.2 +/- 1.1 MUM. The acidic and basic CHCl3 partitions, compounds 1 and 7, and 5-7 mixture were subjected to the tetrad assay, of which the acidic partition displayed decreased locomotion and increased catalepsy, antinociception, and hypothermia in animal at doses of 75-100 mg/kg/ip, and also showed clonic-tonic seizures upon touch at 100mg/kg. CONCLUSION: Bioassay-guided isolation revealed compounds 5-7, 10, and the mixture of LA and PA displayed various degrees of opioid receptor radioligand displacement affinities. The in vivo tetrad assay of acidic CHCl3 partition, enriched with aporphines 1 and 2, displayed actions on all four points of behavioral parameters. It can be concluded that the in vivo mild canabimimetic-type effect observed for the CHCl3 partition is likely mediated through other CNS mechanisms since the extracts, partitions, and isolated compounds had no affinity for the in vitro CB1 and CB2 receptors. This work, along with traditional use and the reported bioactivities of the BTIQ alkaloids, suggested further studies on N. nucifera are needed to understand the roles that the extracts and/or individual compounds might contribute to the behavioral effects. PMID- 26260437 TI - Diffusion imaging of nigral alterations in early Parkinson's disease with dopaminergic deficits. AB - BACKGROUND: This study reports the baseline characteristics of diffusion tensor imaging data in Parkinson's disease (PD) patients and healthy control subjects from the Parkinson's Progression Markers Initiative. The main goals were to replicate previous findings of abnormal diffusion imaging values from the substantia nigra. in a large multicenter cohort and determine whether nigral diffusion alterations are associated with dopamine deficits. METHODS: Two hundred twenty subjects (PD = 153; control = 67) from 10 imaging sites were included. All subjects had a full neurological exam, a ((123) I)ioflupane dopamine transporter (DAT) single-photon emission computer tomography scan, and diffusion tensor imaging. Fractional anisotropy as well as radial and axial diffusivity was computed within multiple regions across the substantia nigra. RESULTS: A repeated measures analysis of variance found a marginally nonsignificant interaction between regional fractional anisotropy of the substantia nigra and disease status (P = 0.08), conflicting with an earlier study. However, a linear mixed model that included control regions in addition to the nigral regions revealed a significant interaction between regions and disease status (P = 0.002), implying a characteristic distribution of reduced fractional anisotropy across the substantia nigra in PD. Reduced fractional anisotropy in PD was also associated with diminished DAT binding ratios. Both axial and radial diffusivity were also abnormal in PD. CONCLUSIONS: Although routine nigral measurements of fractional anisotropy are clinically not helpful, the findings in this study suggest that more-sophisticated diffusion imaging protocols should be used when exploring the clinical utility of this imaging modality. PMID- 26260438 TI - GluN2B-containing NMDA receptors are upregulated in plasma membranes by the sphingosine-1-phosphate analog FTY720P. AB - Sphingosine-1-phosphate (S1P) is a ceramide derivative serving not only as a regulator of immune properties but also as a modulator of brain functions. To better understand the mechanism underlying the effects of S1P on brain functions, we investigated the potential impact of S1P receptor (S1PR) activation on NMDA receptor subunits. We used acute rat hippocampal slices as a model system, and determined the effects of the active phosphorylated S1P analog, fingolimod (FTY720P) on various NMDA receptors. Treatment with FTY720P significantly increased phosphorylation of GluN2B-containing NMDA receptors at Tyr1472. This effect appears rather specific, as treatment with FTY720P did not modify GluN2B Tyr1336, GluN2B-Ser1480, GluN2A-Tyr1325 or GluN1-Ser897 phosphorylation. Pre treatment of hippocampal slices with the compounds W146 and PP1 indicated that FTY720P-induced GluN2B phosphorylation at Tyr1472 epitopes was dependent on activation of S1PR subunit 1 (S1PR1) and Src/Fyn kinase, respectively. Cell surface biotinylation experiments indicated that FTY720P-induced GluN2B phosphorylation at Tyr1472 was also associated with increased levels of GluN1 and GluN2B subunits on membrane surface, whereas no change was observed for GluN2A subunits. We finally demonstrate that FTY720P is inclined to favor Tau and Fyn accumulation on plasma membranes. These results suggest that activation of S1PR1 by FTY720P enhances GluN2B receptor phosphorylation in rat hippocampal slices, resulting in increased levels of GluN1 and GluN2B receptor subunits in neuronal membranes through a mechanism probably involving Fyn and Tau. PMID- 26260440 TI - Relationship between ethical work climate and nurses' perception of organizational support, commitment, job satisfaction and turnover intent. AB - BACKGROUND: Healthcare organizations are now challenged to retain nurses' generation and understand why they are leaving their nursing career prematurely. Acquiring knowledge about the effect of ethical work climate and level of perceived organizational support can help organizational leaders to deal effectively with dysfunctional behaviors and make a difference in enhancing nurses' dedication, commitment, satisfaction, and loyalty to their organization. PURPOSE: This study aims to determine the relationship between ethical work climate, and perceived organizational support and nurses' organizational commitment, job satisfaction, and turnover intention. METHODS: A descriptive correlational research design was conducted in all inpatient care units at three major hospitals affiliated to different health sectors at Alexandria governorate. All nurses working in these previous hospitals were included in the study (N = 500). Ethical Climate Questionnaire, Survey of Perceived Organizational Support, Organizational Commitment Questionnaire, Index of Job Satisfaction, and Intention to Turnover scale were used to measure study variables. Ethical considerations: Approval was obtained from Ethics Committee at Faculty of Nursing, Alexandria University. Privacy and confidentiality of data were maintained and assured by obtaining subjects' informed consent to participate in the research before data collection. FINDINGS: The result revealed positive significant correlations between nurses' perception of overall ethical work climate and each of perceived organizational support, commitment, as well as their job satisfaction. However, negative significant correlations were found between nurses' turnover intention and each of these variables. Also, approximately 33% of the explained variance of turnover intention is accounted by ethical work climate, organizational support, organizational commitment, and job satisfaction, and these variables independently contributed significantly in the prediction of turnover intention. RECOMMENDATION: Strategies to foster and enhance ethical and supportive work climates as well as job-related benefits are considered significant factors in increasing nurses' commitment and satisfaction and decreasing their turnover intention. PMID- 26260439 TI - Evolution, ecology and systematics of Soldanella (Primulaceae) in the southern Apennines (Italy). AB - BACKGROUND: The populations of Soldanella (Primulaceae) of the southern Apennines (Italy) are unique within the genus for their distribution and ecology. Their highly fragmented distribution range, with three main metapopulations on some of the highest mountains (Gelbison, Sila and Aspromonte massifs) of the area, poses intriguing questions about their evolutionary history and biogeography, and about the possibility of local endemisms. AIMS AND METHODS: In order to clarify the phylogeny and biogeography of the three metapopulations of Soldanella in the southern Apennines, attributed to S. calabrella to date, and to identify possible local endemisms, a comparative approach based on the study of molecular, morphological and ecological characteristics of the populations was employed. Specifically, one nuclear (total ITS) and two plastid (rbcL and trnL) markers were used for the phylogenetic analyses, performed through both maximum likelihood and Bayesian techniques. Among the morphological features, the glandular hair and leaf biometric traits were analysed, and the environment in which the populations grew was characterised for altitude, forest canopy composition and soil pH, C, N and organic matter. RESULTS AND CONCLUSIONS: Our findings demonstrate that the lineage of Soldanella of southern Italy diverged from the Carpathians lineage during the Middle Pleistocene, and underwent an evolutionary radiation during the Late Pleistocene. The populations of the Sila and Aspromonte massifs diverged from the populations of the Gelbison massif around 380000 years ago and are probably undergoing a progressive differentiation due to their isolation. The populations on the Gelbison massif, moreover, have different morphological features from those of the Sila and Aspromonte massifs and a different ecological niche. The molecular, morphological and ecological data clearly demonstrate that the metapopulation of Soldanella on the Gelbison massif belongs to a new taxonomic unit at the species level, which we name Soldanella sacra A. & L. Bellino from the name of the massif on which it was discovered, the "Holy Mountain". PMID- 26260441 TI - What is dignity in prehospital emergency care? AB - BACKGROUND: Ethics and dignity in prehospital emergency care are important due to vulnerability and suffering. Patients can lose control of their body and encounter unfamiliar faces in an emergency situation. OBJECTIVE: To describe what specialist ambulance nurse students experienced as preserved and humiliated dignity in prehospital emergency care. RESEARCH DESIGN: The study had a qualitative approach. METHOD: Data were collected by Flanagan's critical incident technique. The participants were 26 specialist ambulance nurse students who described two critical incidents of preserved and humiliated dignity, from prehospital emergency care. Data consist of 52 critical incidents and were analyzed with interpretive content analysis. Ethical considerations: The study followed the ethical principles in accordance with the Declaration of Helsinki. FINDINGS: The result showed how human dignity in prehospital emergency care can be preserved by the ambulance nurse being there for the patient. The ambulance nurses meet the patient in the patient's world and make professional decisions. The ambulance nurse respects the patient's will and protects the patient's body from the gaze of others. Humiliated dignity was described through the ambulance nurse abandoning the patient and by healthcare professionals failing, disrespecting, and ignoring the patient. DISCUSSION: It is a unique situation when a nurse meets a patient face to face in a critical life or death moment. The discussion describes courage and the ethical vision to see another human. CONCLUSION: Dignity was preserved when the ambulance nurse showed respect and protected the patient in prehospital emergency care. The ambulance nurse students' ethical obligation results in the courage to see when a patient's dignity is in jeopardy of being humiliated. Humiliated dignity occurs when patients are ignored and left unprotected. This ethical dilemma affects the ambulance nurse students badly due to the fact that the morals and attitudes of ambulance nurses are reflected in their actions toward the patient. PMID- 26260442 TI - Attributes of a good nurse. AB - BACKGROUND: The opinions of students regarding the attributes of a good nurse can make a major contribution to the planning and the conducting of professional education. There are few studies which aim at identifying the qualifications of a good nurse from the perspectives of nursing students. OBJECTIVES: To determine the opinions of first- and fourth-year nursing students concerning the 'attributes of a good nurse', and whether and how their views change depending on their year of study. RESEARCH DESIGN: Descriptive research. Participants and research context: This study was conducted in the nursing department of a vocational school of health in the 2010/2011 academic year. The study participants consisted of first-year and intern students. A survey form was used to identify characteristics of participants, and students were asked the following open-ended question about their opinions related to the attributes of a good nurse. Ethical considerations: The permission was taken from the school administration. Informed consent was obtained, and anonymity was ensured for participating students. FINDINGS: A total of 120 students participated in this study. Most frequently expressed attributes were 'professional competence' in first-year and 'responsibility' in fourth-year students. While first-year students placed a greater emphasis on the attributes of 'geniality', 'patience', 'calmness', 'love of nursing', 'loyalty to nursing' and 'not attaching importance to material values', fourth-year students emphasized the attributes of 'empathy', 'honesty', 'responsibility' and 'scientific curiosity' significantly more. DISCUSSION AND CONCLUSION: Fourth-year students placed a greater emphasis on the attributes which the students are expected to acquire through a nursing program and clinical experience. However, they mentioned the attributes related to a good nurse-patient relationship and communication significantly less. Appropriate ethical training methods and good role models can help students acquire attributes that are important for the nursing profession and combine them with the attributes they already have. PMID- 26260443 TI - Coagulation of beta-conglycinin, glycinin and isoflavones induced by calcium chloride in soymilk. AB - The coagulation of beta-conglycinin (7S), glycinin (11S) and isoflavones induced by calcium chloride was investigated. Approximately 92.6% of the soymilk proteins were coagulated into the soymilk pellet fraction (SPF) after the addition of 5 mM calcium chloride. SDS-PAGE and two-dimensional electrophoresis analysis indicated that most of the 7S (alpha', alpha and beta), 11S acidic (A1a, A1b, A2, A3 and A4) and 11S basic (B1a) proteins in the SSF were coagulated into the SPF after treatment with 5 mM calcium chloride. Isoflavones, including daidzein and genistein, were also coagulated into the SPF after the addition of 5 mM calcium chloride. The amounts of daidzein and genistein in the SSF decreased to 39.4 +/- 1.6 and 11.8 +/- 7.0%, respectively. HPLC analysis suggested that daidzein and genistein were bound with 7S and 11S proteins and then were coprecipitated into the SPF by 5 mM calcium chloride. PMID- 26260444 TI - Urinothorax: a rare finding after urinary intervention. AB - INTRODUCTION: We report a case in our center of unilateral urinothorax that occurred post percutaneous nephrolithotomy as a rare cause of pleural effusion and acute dyspnea. METHODS: Report of a case. RESULTS: Initial chest CT showed massive left sided pleural effusion from which biochemical investigations revealed exudative effusion and urinothorax. The effusion was drained by central venous pressure catheter and urologic problem was resolved. CONCLUSIONS: urinothorax should be suspected as a cause of pleural effusion in obstructive uropathy and post renal and ureteric maneuvers. PMID- 26260445 TI - Knowledge of and preferences for health insurance among formal sector employees in Addis Ababa: a qualitative study. AB - BACKGROUND: The Ethiopian health system has been undergoing through reforms. One of the reforms stipulated in policy documents is the introduction of health insurance at national level. Having the majority of the population without any experience of health insurance, investigating preferences and knowledge of the essence of health insurance among potential enrolees will provide vital information for policy makers. This formative study seeks to explore the knowledge and the preference for health insurance among formal sector employees in Addis Ababa. METHODS: Six focus group discussions with formal sector employees and five key informant interviews were conducted in Addis Ababa. A thematic analysis is used to analyse the results. RESULTS: The findings suggest that there is little knowledge about the concept and elements of health insurance. Some concepts such as, risk pooling and sharing are not well understood. The participants of the study considered health insurance as only a prepayment mechanism without risk sharing among members of the scheme. Regarding preference for health insurance, they have revealed quality of care as the most important factor. Comprehensiveness of benefit packages and the amount of premium level are also found to be concerns related to health insurance. However, a trade-off is also observed among premium level, comprehensive benefit packages, and healthcare facilities. CONCLUSIONS: Improvements on availability and quality of services need to precede the introduction of social health insurance. There is also a need to work on awareness creation regarding concepts of health insurance. Further studies may explore if the knowledge gap is real or appeared due to reservations of the participants on the introduction of health insurance. PMID- 26260446 TI - Amelioration of the reduced antinociceptive effect of morphine in the unpredictable chronic mild stress model mice by noradrenalin but not serotonin reuptake inhibitors. AB - BACKGROUND: Although alterations in not only the pain sensitivity but also the analgesic effects of opioids have been reported under conditions of stress, the influence of unpredictable chronic mild stress (UCMS) on the antinociceptive effects of opioid analgesics remains to be fully investigated. The present study examined the influence of UCMS on the thermal pain sensitivity and antinociceptive effects of two opioid analgesics, morphine (an agonist of opioid receptors) and tramadol (an agonist of MU-opioid receptor and an inhibitor of both noradrenaline and serotonin transporters). We also examined the effects of pretreatment with maprotiline (a noradrenaline reuptake inhibitor) and escitalopram (a serotonin reuptake inhibitor) on the antinociceptive action of morphine in mice under an UCMS condition. RESULTS: Unpredictable chronic mild stress did not affect the basal thermal pain sensitivity in a mouse hot-plate test. Although morphine dose-dependently induced thermal antinociceptive effects under both the UCMS and non-stress conditions, the thermal antinociceptive effect of 3 mg/kg morphine under the UCMS condition was significantly lower than under the non-stressed condition. Unlike the case with morphine, we observed no significant difference in the thermal antinociceptive effect of tramadol between the UCMS and non-stress conditions. Furthermore, the reduced thermal antinociceptive effect of 3 mg/kg morphine under the UCMS condition was significantly ameliorated by pretreatment with 10 mg/kg maprotiline but not 3 mg/kg escitalopram. Pretreatment with neither maprotiline nor escitalopram alone was associated with an antinociceptive effect under either condition. CONCLUSIONS: We demonstrated that the antinociceptive effect of morphine but not tramadol was reduced in mice that had experienced UCMS. The reduced antinociceptive effect of morphine under the UCMS condition was ameliorated by pretreatment with maprotiline but not escitalopram. These results suggest that the reduced antinociceptive effects of morphine under conditions of chronic stress may be ameliorated by activation of the noradrenergic but not the serotonergic system. PMID- 26260447 TI - Antitumor efficacy of extracellular complexes with gadolinium in Binary Radiotherapy. AB - In this report the efficacy of extracellular pharmaceutical Gd-DTPA in Binary Radiotherapy was studied. The study was carried out in mice bearing transplantable adenocarcinoma Ca755 using X-ray based contrast enhanced radiotherapy as a practical implementation of Binary Radiotherapy. It was shown that intravenous administration of 0.3 ml of 0.5 M water solution of Gd-DTPA followed by X-irradiation at a dose of 10 Gy provides T/C%=10+/-3% and leads to complete tumor regression in 25% of mice. PMID- 26260448 TI - Development of beryllium-based neutron target system with three-layer structure for accelerator-based neutron source for boron neutron capture therapy. AB - The iBNCT project team with University of Tsukuba is developing an accelerator based neutron source. Regarding neutron target material, our project has applied beryllium. To deal with large heat load and blistering of the target system, we developed a three-layer structure for the target system that includes a blistering mitigation material between the beryllium used as the neutron generator and the copper heat sink. The three materials were bonded through diffusion bonding using a hot isostatic pressing method. Based on several verifications, our project chose palladium as the intermediate layer. A prototype of the neutron target system was produced. We will verify that sufficient neutrons for BNCT treatment are generated by the device in the near future. PMID- 26260449 TI - Localized radiation necrosis model in mouse brain using proton ion beams. AB - Brain radiation necrosis is the most serious late adverse event that occurs after 6 months following radiation therapy. Effective treatment for this irreversible brain necrosis has not been established yet. This study tries to establish brain radiation necrosis mouse model using proton or helium beam. The right cerebral hemispheres of C57BL/6J mouse brains were irradiated at doses of 40, 50, 60 Gy with charged particles. In 60 Gy group, brain necrosis that recapitulates human disease was detected after 8 months. PMID- 26260450 TI - Alteration of Upstream Autophagy-Related Proteins (ULK1, ULK2, Beclin1, VPS34 and AMBRA1) in Lewy Body Disease. AB - Autophagy is associated with the pathogenesis of Lewy body disease, including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). It is known that several downstream autophagosomal proteins are incorporated into Lewy bodies (LBs). We performed immunostaining and Western blot analysis using a cellular model of PD and human brain samples to investigate the involvement of upstream autophagosomal proteins (ULK1, ULK2, Beclin1, VPS34 and AMBRA1), which initiate autophagy and form autophagosomes. Time course analysis of cultured cells transfected with flag-alpha-synuclein and synphilin-1 revealed upregulation of these upstream proteins with accumulation of LB-like inclusions. In human specimens, only mature LBs were positive for upstream autophagosomal proteins. Western blotting of fractionated brain lysates showed that upstream autophagosomal proteins were detected in the soluble and insoluble fraction in DLB, corresponding to the bands of phosphorylated alpha-synuclein. However, Western blot analysis of total brain lysates in PD and DLB showed that the increase of upstream autophagosomal proteins was only partial. The quantitative, qualitative and locational alteration of upstream autophagosomal proteins in the present study indicates their involvement in the pathogenesis of LB disease. Our data also suggest that misinduction or impairment of upstream autophagy might occur in the disease process of LB disease. PMID- 26260451 TI - Immunoglobulin Fc-fused, neuropilin-1-specific peptide shows efficient tumor tissue penetration and inhibits tumor growth via anti-angiogenesis. AB - Neuropilin-1 (NRP1) receptor, involved in vascular endothelial growth factor (VEGF)-mediated vascular permeability and tumor angiogenesis, is targeted by peptides that bind to its VEGF-binding site. However, these peptides also cross react with the structurally related receptor, NRP2. Here, we describe an immunoglobulin Fc-fused peptide, Fc-TPP11, which specifically binds to the VEGF binding site of NRP1 with approximately 2nM affinity, but negligibly to that of NRP2. Fc-TPP11 triggered NRP1-dependent signaling, enhanced vascular permeability via vascular endothelial (VE)-cadherin downregulation, and increased paracellular permeability via E-cadherin downregulation in tumor tissues. Fc-TPP11 also significantly enhanced the tumor penetration of co-injected anti-cancer drug, doxorubicin, leading to the improved in vivo anti-tumor efficacy. Fc-TPP11 was easily adapted to the full-length anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) cetuximab (Erbitux), cetuximab-TPP11, exhibiting more than 2-fold improved tumor penetration than the parent cetuximab. Fc-TPP11 exhibited a similar whole-body half-life to that of intact Fc in tumor bearing mice. In addition to the tumor-penetrating activity, Fc-TPP11 suppressed VEGF dependent angiogenesis by blocking VEGF binding to NRP1, thereby inhibiting tumor growth without promoting metastasis in the mouse model. Our results show that NRP1-specific, high-affinity binding of Fc-TPP11, is useful to validate NRP1 signaling, independent of NRP2. Thus, Fc-TPP11 can be used as a tumor penetration promoting agent with anti-angiogenic activity or directly adapted to mAb-TPP11 format for more potent anti-cancer antibody therapy. PMID- 26260452 TI - Hyaluronidase-incorporated hyaluronic acid-tyramine hydrogels for the sustained release of trastuzumab. AB - We developed an injectable hydrogel system for the sustained release of protein drugs that incorporated both protein drugs and hyaluronidase. Trastuzumab and hyaluronidase were incorporated in hydrogels composed of hyaluronic acid-tyramine (HA-Tyr) conjugates through the enzymatic crosslinking utilizing hydrogen peroxide (H2O2) and horseradish peroxidase (HRP). Through electrostatic interactions with the HA, trastuzumab was retained in the hydrogel to minimize its burst release. Hyaluronidase was incorporated in the hydrogel to release trastuzumab from the hydrogels. The hydrogels were degraded and showed sustained release of trastuzumab in phosphate buffer over four weeks in vitro. Both the rates of drug release and gel degradation were controlled by the concentration of hyaluronidase. Trastuzumab released from the hydrogels inhibited the proliferation of BT-474 cells in vitro. In an animal model, the single subcutaneous injection of a mixture solution of HA-Tyr conjugates, H2O2, HRP, trastuzumab and hyaluronidase inhibited tumor growth significantly, whereas injection of trastuzumab alone at the same dose failed to do so. Compared to trastuzumab alone, the hyaluronidase-incorporated HA-Tyr hydrogels improved the pharmacokinetic profile of trastuzumab in the plasma of mice. Furthermore, they were fully degraded over two weeks, and the formation of fibrous capsules was not observed in mice. PMID- 26260453 TI - Divergent responses of inflammatory mediators within the amygdala and medial prefrontal cortex to acute psychological stress. AB - There is now a growing body of literature that indicates that stress can initiate inflammatory processes, both in the periphery and brain; however, the spatiotemporal nature of this response is not well characterized. The aim of this study was to examine the effects of an acute psychological stress on changes in mRNA and protein levels of a wide range of inflammatory mediators across a broad temporal range, in key corticolimbic brain regions involved in the regulation of the stress response (amygdala, hippocampus, hypothalamus, medial prefrontal cortex). mRNA levels of inflammatory mediators were analyzed immediately following 30min or 120min of acute restraint stress and protein levels were examined 0h through 24h post-termination of 120min of acute restraint stress using both multiplex and ELISA methods. Our data demonstrate, for the first time, that exposure to acute psychological stress results in an increase in the protein level of several inflammatory mediators in the amygdala while concomitantly producing a decrease in the protein level of multiple inflammatory mediators within the medial prefrontal cortex. This pattern of changes seemed largely restricted to the amygdala and medial prefrontal cortex, with stress producing few changes in the mRNA or protein levels of inflammatory mediators within the hippocampus or hypothalamus. Consistent with previous research, stress resulted in a general elevation in multiple inflammatory mediators within the circulation. These data indicate that neuroinflammatory responses to stress do not appear to be generalized across brain structures and exhibit a high degree of spatiotemporal specificity. Given the impact of inflammatory signaling on neural excitability and emotional behavior, these data may provide a platform with which to explore the importance of inflammatory signaling within the prefrontocortical amygdala circuit in the regulation of the neurobehavioral responses to stress. PMID- 26260454 TI - MicroRNA-200c and microRNA-31 regulate proliferation, colony formation, migration and invasion in serous ovarian cancer. AB - BACKGROUND: Serous epithelial ovarian cancer (SEOC) is a highly metastatic disease and its progression has been implicated with microRNAs. This study aimed to identify the differentially expressed microRNAs in Malaysian patients with SEOC and examine the microRNAs functional roles in SEOC cells. METHODS: Twenty two SEOC and twenty-two normal samples were subjected to miRNA expression profiling using the locked nucleic acid (LNA) quantitative real-time PCR (qPCR). The localization of miR-200c was determined via LNA in situ hybridization (ISH). Functional analysis of miR-200c and miR-31 on cell proliferation, migration and invasion and clonogenic cell survival were assessed in vitro. The putative target genes of the two miRNAs were predicted by miRWalk program and expression of the target genes in SEOC cell lines was validated. RESULTS: The miRNA expression profiling revealed thirty-eight significantly dysregulated miRNAs in SEOC compared to normal ovarian tissues. Of these, eighteen were up-regulated whilst twenty miRNAs were down-regulated. We observed chromogenic miR-200c-ISH signal predominantly in the cytoplasmic compartment of both epithelial and inflammatory cancer cells. Re-expression of miR-200c significantly increased the cell proliferation and colony formation but reduced the migration and invasion of SEOC cells. In addition, miR-200c expression was inversely proportionate with the expression of deleted in liver cancer-1 (DLC-1) gene. Over-expression of miR-31 in SEOC cells resulted in decreased cell proliferation, clonogenic potential, cell migration and invasion. Meanwhile, miR-31 gain-of-function led to the down regulation of AF4/FMR2 family member 1 (AFF1) gene. CONCLUSIONS: These data suggested that miR-200c and miR-31 may play roles in the SEOC metastasis biology and could be considered as promising targets for therapeutic purposes. PMID- 26260455 TI - Origin and Impact of Nitric Oxide in Pseudomonas aeruginosa Biofilms. AB - The formation of the organized bacterial community called biofilm is a crucial event in bacterial physiology. Given that biofilms are often refractory to antibiotics and disinfectants to which planktonic bacteria are susceptible, their formation is also an industrially and medically relevant issue. Pseudomonas aeruginosa, a well-known human pathogen causing acute and chronic infections, is considered a model organism to study biofilms. A large number of environmental cues control biofilm dynamics in bacterial cells. In particular, the dispersal of individual cells from the biofilm requires metabolic and morphological reprogramming in which the second messenger bis-(3'-5')-cyclic dimeric GMP (c-di GMP) plays a central role. The diatomic gas nitric oxide (NO), a well-known signaling molecule in both prokaryotes and eukaryotes, is able to induce the dispersal of P. aeruginosa and other bacterial biofilms by lowering c-di-GMP levels. In this review, we summarize the current knowledge on the molecular mechanisms connecting NO sensing to the activation of c-di-GMP-specific phosphodiesterases in P. aeruginosa, ultimately leading to c-di-GMP decrease and biofilm dispersal. PMID- 26260456 TI - Loss of Antibiotic Tolerance in Sod-Deficient Mutants Is Dependent on the Energy Source and Arginine Catabolism in Enterococci. AB - Enterococci are naturally tolerant to typically bactericidal cell wall-active antibiotics, meaning that their growth is inhibited but they are not killed even when exposed to a high concentration of the drug. The molecular reasons for this extraordinary tolerance are still incompletely understood. Previous work showed that resistance to killing collapsed specifically in mutants affected in superoxide dismutase (Sod) activity, arguing that bactericidal antibiotic treatment led to induction of a superoxide burst. In the present work, we show that loss of antibiotic tolerance in DeltasodA mutants of pathogenic enterococci is dependent on the energy source present during antibiotic treatment. Hexoses induce greater killing than the pentose ribose, and no killing was observed with glycerol as the energy source. These results point to glycolytic reactions as crucial for antibiotic-mediated killing of DeltasodA mutants. A transposon mutant library was constructed in Enterococcus faecalis DeltasodA mutants and screened for restored tolerance of vancomycin. Partially restored tolerance was observed in mutants with transposon integrations into intergenic regions upstream of regulators implicated in arginine catabolism. In these mutants, the arginine deiminase operon was highly upregulated. A model for the action of cell wall active antibiotics in tolerant and nontolerant bacteria is proposed. IMPORTANCE: Antibiotic tolerance is a serious clinical concern, since tolerant bacteria have considerably increased abilities to resist killing by bactericidal drugs. Using enterococci as models for highly antibiotic-tolerant pathogens, we showed that tolerance of these bacteria is linked to their superoxide dismutase (Sod), arguing that bactericidal antibiotics induce generation of reactive oxygen species inside cells. Wild-type strains are tolerant because they detoxify these deleterious molecules by the activity of Sod, whereas Sod-deficient strains are killed. This study showed that killing depends on the energy source present during treatment and that an increase in arginine catabolism partially restored tolerance of the Sod mutants. These results are used to propose a mode-of-action model of cell wall-active antibiotics in tolerant and nontolerant bacteria. PMID- 26260457 TI - Cross Talk Inhibition Nullified by a Receiver Domain Missense Substitution. AB - In two-component signal transduction, a sensor protein transmitter module controls cognate receiver domain phosphorylation. Most receiver domain sequences contain a small residue (Gly or Ala) at position T + 1 just distal to the essential Thr or Ser residue that forms part of the active site. However, some members of the NarL receiver subfamily have a large hydrophobic residue at position T + 1. Our laboratory previously isolated a NarL mutant in which the T + 1 residue Val-88 was replaced with an orthodox small Ala. This NarL V88A mutant confers a striking phenotype in which high-level target operon expression is both signal (nitrate) and sensor (NarX and NarQ) independent. This suggests that the NarL V88A protein is phosphorylated by cross talk from noncognate sources. Although cross talk was enhanced in ackA null strains that accumulate acetyl phosphate, it persisted in pta ackA double null strains that cannot synthesize this compound and was observed also in narL(+) strains. This indicates that acetate metabolism has complex roles in mediating NarL cross talk. Contrariwise, cross talk was sharply diminished in an arcB barA double null strain, suggesting that the encoded sensors contribute substantially to NarL V88A cross talk. Separately, the V88A substitution altered the in vitro rates of NarL autodephosphorylation and transmitter-stimulated dephosphorylation and decreased affinity for the cognate sensor, NarX. Together, these experiments show that the residue at position T + 1 can strongly influence two distinct aspects of receiver domain function, the autodephosphorylation rate and cross talk inhibition. IMPORTANCE: Many bacterial species contain a dozen or more discrete sensor response regulator two-component systems that convert a specific input into a distinct output pattern. Cross talk, the unwanted transfer of signals between circuits, occurs when a response regulator is phosphorylated inappropriately from a noncognate source. Cross talk is inhibited in part by the high interaction specificity between cognate sensor-response regulator pairs. This study shows that a relatively subtle missense change from Val to Ala nullifies cross talk inhibition, enabling at least two noncognate sensors to enforce an inappropriate output independently of the relevant input. PMID- 26260458 TI - Regulation of the Expression of De Novo Pyrimidine Biosynthesis Genes in Corynebacterium glutamicum. AB - Expression of pyrimidine de novo biosynthesis is downregulated by an exogenous uracil in many bacteria. In this study, we show that a putative binding motif sequence of PyrR is required for uracil-mediated repression of pyrR-lacZ translational fusion. However, the uracil response was still observed in the strain with the pyrR gene deleted, implying the existence of a uracil response factor other than PyrR which also acts through the PyrR binding loop region. Deletion of rho, encoding the transcription termination factor Rho, resulted in an increase in the expression of pyrR-lacZ. Moreover, the strain with a double deletion of pyrR and rho showed elimination of the uracil-responsive downregulation of the pyrR-lacZ. Therefore, expression of the pyrimidine biosynthetic gene cluster in Corynebacterium glutamicum is controlled by two different mechanisms mediated by PyrR and Rho. IMPORTANCE: The pyr genes of C. glutamicum are downregulated in the presence of uracil in culture medium. The mRNA binding regulator PyrR represses the expression of pyr genes, as reported previously. However, the uracil response was still observed in the pyrR deletion strain. Deletion of rho in addition to pyrR deletion results in the elimination of the uracil response. Therefore, we identified the factors that are involved in the uracil response. Involvement of Rho in the regulation of pyrimidine de novo biosynthesis genes has not been reported. PMID- 26260459 TI - Dps and DpsL Mediate Survival In Vitro and In Vivo during the Prolonged Oxidative Stress Response in Bacteroides fragilis. AB - Bacteroides fragilis is a Gram-negative anaerobe and member of the human intestinal tract microbiome, where it plays many beneficial roles. However, translocation of the organism to the peritoneal cavity can lead to peritonitis, intra-abdominal abscess formation, bacteremia, and sepsis. During translocation, B. fragilis is exposed to increased oxidative stress from the oxygenated tissues of the peritoneal cavity and the immune response. In order to survive, B. fragilis mounts a robust oxidative stress response consisting of an acute and a prolonged oxidative stress (POST) response. This report demonstrates that the ability to induce high levels of resistance to tert-butyl hydroperoxide (tBOOH) after extended exposure to air can be linked to the POST response. Disk diffusion assays comparing the wild type to a Deltadps mutant and a Deltadps Deltabfr mutant showed greater sensitivity of the mutants to tBOOH after exposure to air, suggesting that Dps and DpsL play a role in the resistance phenotype. Complementation studies with dps or bfr (encoding DpsL) restored tBOOH resistance, suggesting a role for both of these ferritin-family proteins in the response. Additionally, cultures treated with the iron chelator dipyridyl were not killed by tBOOH, indicating Dps and DpsL function by sequestering iron to prevent cellular damage. An in vivo animal model showed that the Deltadps Deltabfr mutant was attenuated, indicating that management of iron is important for survival within the abscess. Together, these data demonstrate a role for Dps and DpsL in the POST response which mediates survival in vitro and in vivo. IMPORTANCE: B. fragilis is the anaerobe most frequently isolated from extraintestinal opportunistic infections, but there is a paucity of information about the factors that allow this organism to survive outside its normal intestinal environment. This report demonstrates that the iron storage proteins Dps and DpsL protect against oxidative stress and that they contribute to survival both in vitro and in vivo. Additionally, this work demonstrates an important role for the POST response in B. fragilis survival and provides insight into the complex regulation of this response. PMID- 26260460 TI - NanI Sialidase, CcpA, and CodY Work Together To Regulate Epsilon Toxin Production by Clostridium perfringens Type D Strain CN3718. AB - Clostridium perfringens type D strains are usually associated with diseases of livestock, and their virulence requires the production of epsilon toxin (ETX). We previously showed (J. Li, S. Sayeed, S. Robertson, J. Chen, and B. A. McClane, PLoS Pathog 7:e1002429, 2011, http://dx.doi.org/10.1371/journal.ppat.1002429) that BMC202, a nanI null mutant of type D strain CN3718, produces less ETX than wild-type CN3718 does. The current study proved that the lower ETX production by strain BMC202 is due to nanI gene disruption, since both genetic and physical (NanI or sialic acid) complementation increased ETX production by BMC202. Furthermore, a sialidase inhibitor that interfered with NanI activity also reduced ETX production by wild-type CN3718. The NanI effect on ETX production was shown to involve reductions in codY and ccpA gene transcription levels in BMC202 versus wild-type CN3718. Similar to CodY, CcpA was found to positively control ETX production. A double codY ccpA null mutant produced even less ETX than a codY or ccpA single null mutant. CcpA bound directly to sequences upstream of the etx or codY start codon, and bioinformatics identified putative CcpA-binding cre sites immediately upstream of both the codY and etx start codons, suggesting possible direct CcpA regulatory effects. A ccpA mutation also decreased codY transcription, suggesting that CcpA effects on ETX production can be both direct and indirect, including effects on codY transcription. Collectively, these results suggest that NanI, CcpA, and CodY work together to regulate ETX production, with NanI-generated sialic acid from the intestines possibly signaling type D strains to upregulate their ETX production and induce disease. IMPORTANCE: Clostridium perfringens NanI was previously shown to increase ETX binding to, and cytotoxicity for, MDCK host cells. The current study demonstrates that NanI also regulates ETX production via increased transcription of genes encoding the CodY and CcpA global regulators. Results obtained using single ccpA or codY null mutants and a ccpA codY double null mutant showed that codY and ccpA regulate ETX production independently of one another but that ccpA also affects codY transcription. Electrophoretic mobility shift assays and bioinformatic analyses suggest that both CodY and CcpA may directly regulate etx transcription. Collectively, results of this study suggest that sialic acid generated by NanI from intestinal sources signals ETX-producing C. perfringens strains, via CcpA and CodY, to upregulate ETX production and cause disease. PMID- 26260462 TI - The Impact of Spironolactone on the Severity of Portal-Systemic Collaterals and Hepatic Encephalopathy in Cirrhotic Rats. AB - Liver cirrhosis and portal hypertension are accompanied by portal-systemic collaterals formation and lethal complications. Angiogenesis participates in the development of collaterals. Spironolactone is an aldosterone receptor antagonist used to control fluid overload in cirrhotic patients although recent studies suggest that it also inhibits angiogenesis. This study investigated the effect of spironolactone on abnormal angiogenesis and portal-systemic collaterals in cirrhosis. Liver cirrhosis was induced in Sprague-Dawley rats by common bile duct ligation (BDL), and sham-operated rats were the controls. The BDL and sham rats received spironolactone (20 mg/kg/d, oral gavage) or vehicle from day 15 to 28 after the operations. Spironolactone did not influence the portal and systemic hemodynamic, and the renal and hepatic biochemistry data, but it significantly ameliorated hepatic fibrosis, portal-systemic shunting, and mesenteric angiogenesis. Plasma vascular endothelial growth factor (VEGF) levels and the mesenteric protein expression of VEGF and phosphor-vascular endothelial growth factor receptor 2 (VEGFR-2) decreased in the spironolactone group. Spironolactone did not affect motor activity or plasma ammonia levels. The down-regulation of VEGF pathway participates, albeit partly, in the antiangiogenic effect of spironolactone. Thus, spironolactone treatment in patients with liver cirrhosis may provide additional benefits aside from ascites control. PMID- 26260461 TI - Positive Effect of Carbon Sources on Natural Transformation in Escherichia coli: Role of Low-Level Cyclic AMP (cAMP)-cAMP Receptor Protein in the Derepression of rpoS. AB - Natural plasmid transformation of Escherichia coli is a complex process that occurs strictly on agar plates and requires the global stress response factor sigma(S). Here, we showed that additional carbon sources could significantly enhance the transformability of E. coli. Inactivation of phosphotransferase system genes (ptsH, ptsG, and crr) caused an increase in the transformation frequency, and the addition of cyclic AMP (cAMP) neutralized the promotional effect of carbon sources. This implies a negative role of cAMP in natural transformation. Further study showed that crp and cyaA mutations conferred a higher transformation frequency, suggesting that the cAMP-cAMP receptor protein (CRP) complex has an inhibitory effect on transformation. Moreover, we observed that rpoS is negatively regulated by cAMP-CRP in early log phase and that both crp and cyaA mutants show no transformation superiority when rpoS is knocked out. Therefore, it can be concluded that both the crp and cyaA mutations derepress rpoS expression in early log phase, whereby they aid in the promotion of natural transformation ability. We also showed that the accumulation of RpoS during early log phase can account for the enhanced transformation aroused by additional carbon sources. Our results thus demonstrated that the presence of additional carbon sources promotes competence development and natural transformation by reducing cAMP-CRP and, thus, derepressing rpoS expression during log phase. This finding could contribute to a better understanding of the relationship between nutrition state and competence, as well as the mechanism of natural plasmid transformation in E. coli. IMPORTANCE: Escherichia coli, which is not usually considered to be naturally transformable, was found to spontaneously take up plasmid DNA on agar plates. Researching the mechanism of natural transformation is important for understanding the role of transformation in evolution, as well as in the transfer of pathogenicity and antibiotic resistance genes. In this work, we found that carbon sources significantly improve transformation by decreasing cAMP. Then, the low level of cAMP-CRP derepresses the general stress response regulator RpoS via a biphasic regulatory pattern, thereby contributing to transformation. Thus, we demonstrate the mechanism by which carbon sources affect natural transformation, which is important for revealing information about the interplay between nutrition state and competence development in E. coli. PMID- 26260463 TI - A Systematic Review of the Outcomes of Posterolateral Corner Knee Injuries, Part 2: Surgical Treatment of Chronic Injuries. AB - BACKGROUND: There are a variety of reported surgical techniques outcomes of chronic grade III posterolateral corner (PLC) knee injuries. It is unknown if outcomes differ among the various surgical treatments. PURPOSE: To systematically review the literature and report subjective and objective outcomes for surgical treatment strategies for chronic grade III PLC injuries to determine the optimal surgical technique. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A systematic review of the literature including Cochrane, PubMed, Medline, and Embase was performed. The following search terms were used: posterolateral corner knee, posterolateral knee, posterolateral instability, multiligament knee, and knee dislocation. Inclusion criteria were outcome studies of surgical treatment for chronic PLC knee injuries with a minimum 2-year follow up, subjective outcomes, objective outcomes including varus stability, and subgroup data on PLC injuries. Two investigators independently reviewed all abstracts. Accepted definitions of varus stability on examination or stress radiographs, and the need for revision surgery, were used to categorically define success and failure. RESULTS: Fifteen studies with a total of 456 patients were included in this study. The 15 studies included 5 with level 3 evidence and 10 with level 4 evidence. The mean age of the patients in each study ranged from 25.2 to 40 years, the reported mean time to surgery ranged from 5.5 to 52.8 months, and the mean follow-up duration ranged from 2 to 16.3 years. Mean postoperative Lysholm scores ranged from 65.5 to 91.8; mean postoperative International Knee Documentation Committee (IKDC) scores ranged from 62.6 to 86.0. Based on objective stability, there was an overall success rate of 90% and a 10% failure rate of PLC reconstruction. A variety of surgical techniques were reported. CONCLUSION: Chronic PLC injuries were reconstructed in all studies, and while techniques varied, the surgical management of chronic PLC injuries had a 90% success rate and a 10% failure rate according to the individual investigators' examination or stress radiographic assessment of objective outcomes. More than half of the 456 patients had a combined posterior cruciate ligament-PLC injury. Surgical techniques included variations of fibular slings, capsular shifts, and anatomic-based techniques (fibular tunnel and tibial tunnel). Further research is needed to determine the optimal surgical technique for treating chronic grade III PLC injuries. PMID- 26260464 TI - A Systematic Review of the Outcomes of Posterolateral Corner Knee Injuries, Part 1: Surgical Treatment of Acute Injuries. AB - BACKGROUND: There is a paucity of outcome data to guide the surgical treatment of acute grade III posterolateral corner (PLC) knee injuries. PURPOSE: To systematically review the literature to compare clinical outcomes of the treatment for acute grade III PLC injuries. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A systematic review of the literature including Cochrane, PubMed, Medline, and Embase was performed. The following search terms were used: posterolateral corner knee, posterolateral knee, posterolateral instability, multiligament knee, and knee dislocation. Inclusion criteria were outcome studies of surgically treated acute PLC injuries with a minimum 2-year follow-up, subjective outcomes, objective outcomes including varus stability, and subgroup data on PLC injuries. Two investigators independently reviewed all abstracts. Accepted definitions of varus stability on examination or stress radiographs and the need for revision surgery were used to categorically define success and failure. RESULTS: Eight studies with a total of 134 patients were included. The mean patient age was reported in 7 studies (range, 21-31.5 years). The mean time to surgery was reported in 5 studies (range, 15-24.3 days); surgery was performed within 3 weeks in the other 3 studies. Four studies reported International Knee Documentation Committee scores (range, 78.1-91.3); 5 studies reported Lysholm scores (range, 87.5-90.3). Only 3 studies obtained bilateral varus stress radiographs. Based on an objective evaluation with varus stress examinations or radiographs, there was an overall success rate of 81% and failure rate of 19%. In 2 studies, the fibular collateral ligament and popliteus tendon were repaired and staged cruciate reconstruction performed in most patients; there were 17 failures of 45 patients (38%). In the remainder of the studies, patients were treated with local tissue transfer, hybrid repair for amenable structures or reconstruction for midsubstance tears, or reconstruction of all torn structures; the failure rate was 9%. CONCLUSION: The repair of acute grade III PLC injuries and staged treatment of combined cruciate injuries were associated with a substantially higher postoperative PLC failure rate. Further research is required to identify the reconstruction technique that provides optimal subjective and objective outcomes. PMID- 26260465 TI - Chondroinduction Is the Main Cartilage Repair Response to Microfracture and Microfracture With BST-CarGel: Results as Shown by ICRS-II Histological Scoring and a Novel Zonal Collagen Type Scoring Method of Human Clinical Biopsy Specimens. AB - BACKGROUND: Current cartilage repair histological scoring systems are unable to explain the relationship between collagen type II deposition and overall repair quality. PURPOSE/HYPOTHESIS: The purpose of this study was to develop a novel zonal collagen type (ZCT) 5-point scoring system to measure chondroinduction in human clinical biopsy specimens collected after marrow stimulation. The hypothesis was that the ZCT scores would correlate with the International Cartilage Repair Society-II (ICRS-II) overall histological repair assessment score and glycosaminoglycan (GAG) content. STUDY DESIGN: Descriptive laboratory study. METHODS: After optimizing safranin O staining for GAG and immunostaining for human collagen type II and type I (Col2 and Col1, respectively), serial sections from clinical osteochondral repair biopsy specimens (13 months after microfracture or microfracture with BST-CarGel; n = 39 patients) were stained and 3 blinded readers performed histomorphometry for percentage of staining, ICRS-II histological scoring, polarized light microscopy (PLM) scoring, and 5-point ZCT scoring based on tidemark morphology, zonal distribution of Col2 and Col1, and Col1 percentage stain. Because 1 biopsy specimen was missing bone, 38 biopsy specimens were evaluated for ICRS-II, PLM, and ZCT scores. RESULTS: Chondroinduction was identified in 21 biopsy specimens as a Col2 matrix fused to bone that spanned the deep-middle-superficial zones ("full-thickness hyaline repair"), deep-middle zones, or deep zone ("stalled hyaline") that was covered with a variable-thickness Col1-positive matrix, and was scored, respectively, as ZCT = 1 (n = 4 biopsy specimens), ZCT = 2 (n = 6) and ZCT = 3 (n = 11). Other biopsy specimens (n = 17) were fibrocartilage (n = 9; ZCT = 4), fibrous tissue (n = 4, ZCT = 5), or non-marrow derived (n = 4; ZCT = 0). Non-marrow derived tissue had a mean mature tidemark score of 84 out of 100 versus a regenerating tidemark score of 24 for all other biopsy specimens (P = .005). Both "stalled hyaline" repair and fibrocartilage had the same mean Col2 percentage stain; however, fibrocartilage was distinguished by heavy Col1 deposits in the deep zone, a 2 fold higher mean Col1 percentage stain (P = .001), and lower surface integrity (P = .03). ZCT scores correlated with GAG content and the ICRS-II overall assessment score, especially when combined with the PLM score for collagen organization (R = 0.82). Histological scores of the deep zone strongly predicted the ICRS-II overall assessment score (R = 0.99). CONCLUSION: The ICRS-II overall repair assessment score and GAG content correlated with the extent of Col2 deposition free of fibrosis in the deep/middle zone rather than bulk accumulation of Col2. CLINICAL RELEVANCE: Biopsy tissue from the BST-CarGel randomized clinical trial (microfracture without and with BST-CarGel, as treatment groups were not unblinded) showed regenerated tissue consistent with a chondroinduction mechanism in at least half of the treated lesions. PMID- 26260466 TI - Continuous Loop Double Endobutton Reconstruction for Acromioclavicular Joint Dislocation. AB - BACKGROUND: Current anatomic methods for reconstruction of the dislocated acromioclavicular (AC) joint show improved clinical results but continue to be associated with significant rates of fixation loss and complications, limiting more widespread use. PURPOSE: To determine the long-term clinical and radiologic outcomes of a novel surgical technique using a closed-loop double Endobutton device to reconstruct both acute and chronic dislocations. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Between 2003 and 2012, a total of 35 patients (31 men, 4 women) at a mean age of 42 years (range, 25-70 years) were surgically treated for a Rockwood type III or greater AC joint dislocation with the described technique (26 chronic, 9 acute). Imbrication of the AC joint capsule and deltotrapezial fascia was performed in all patients. Biological bridging across the coracoclavicular (CC) interval was performed in all patients by use of coracoacromial (CA) ligament transfer in 28 patients and primary repair of the CC ligament in 7 patients. Complete follow-up information was obtained for 31 of 35 patients. RESULTS: At a mean follow-up of 5.2 years (range, 27-144 months), the construct remained stable in all but 1 patient. The mean CC interval difference was 1.1 mm (range, -2.5 to 4.0 mm) and was <2 mm in 87% of patients. The mean Constant score was 98; the mean University of California, Los Angeles Shoulder Rating Scale score was 34; and the mean American Shoulder and Elbow Surgeons Shoulder Score was 98. Follow-up MRI evaluation in 10 patients consistently demonstrated a wide band of dense scar tissue between the coracoid and clavicle. No infections, fractures, or perioperative complications occurred. CONCLUSION: Excellent results were obtained and maintained over long-term follow up. The continuous loop device eliminated the possibility of knot slippage or breakage. MRI confirmed a robust healing response. The described technique resulted in outcomes that were significantly superior to historical reports of nonsurgical outcomes, and the technique can be recommended both for acute and chronic dislocations. PMID- 26260468 TI - In situ degradation studies of two-dimensional WSe2-graphene heterostructures. AB - Heterostructures of two-dimensional materials can be vulnerable to thermal degradation due to structural and interfacial defects as well as thermal expansion mismatch, yet a systematic study does not exist in the literature. In this study, we investigate the degradation of freestanding WSe2-graphene heterostructures due to heat and charge flow by performing in situ experiments inside a transmission electron microscope. Experimental results show that purely thermal loading requires higher temperatures (>850 degrees C), about 150 degrees C higher than that under combined electrical and thermal loading. In both cases, selenium is the first element to decompose and migration of silicon atoms from the test structure to the freestanding specimen initiates rapid degradation through the formation of tungsten disilicide and silicon carbide. The role of the current flow is to enhance the migration of silicon from the sample holder and to knock-out the selenium atoms. The findings of this study provide fundamental insights into the degradation of WSe2-graphene heterostructures and inspire their application in electronics for use in harsh environments. PMID- 26260469 TI - Effects of Dangkwisoo-san, a traditional herbal medicine for treating pain and blood stagnation, on the pacemaker activities of cultured interstitial cells of Cajal. AB - The interstitial cells of Cajal (ICCs) are the pacemaker cells in the gastrointestinal (GI) tract. In the present study, the effects of Dangkwisoo-san (DS) on pacemaker potentials in cultured ICCs from the small intestine of the mouse were investigated. The whole-cell patch-clamp configuration was used to record pacemaker potentials from cultured ICCs and the increase in intracellular Ca2+ concentration ([Ca2+i) was analyzed in cultured ICCs using fura-2 acetoxymethyl ester. The generation of pacemaker potentials in the ICCs was observed. DS produced pacemaker depolarizations in a concentration dependent manner in current clamp mode. The 4-diphenylacetoxy-N-methyl-piperidine methiodide muscarinic M3 receptor antagonist inhibited DS-induced pacemaker depolarizations, whereas methoctramine, a muscarinic M2 receptor antagonist, did not. When guanosine 5'-[beta-thio] diphosphate (GDP-beta-S; 1 mM) was in the pipette solution, DS marginally induced pacemaker depolarizations, whereas low Na+ solution externally eliminated the generation of pacemaker potentials and inhibited the DS-induced pacemaker depolarizations. Additionally, the nonselective cation channel blocker, flufenamic acid, inhibited the DS-induced pacemaker depolarizations. Pretreatment with Ca2+-free solution and thapsigargin, a Ca2+-ATPase inhibitor in the endoplasmic reticulum, also eliminated the generation of pacemaker currents and suppressed the DS-induced pacemaker depolarizations. In addition, [Ca2+]i analysis revealed that DS increased [Ca2+]i. These results suggested that DS modulates pacemaker potentials through muscarinic M3 receptor activation in ICCs by G protein-dependent external and internal Ca2+ regulation and external Na+. Therefore, DS were observed to affect intestinal motility through ICCs. PMID- 26260470 TI - UV-responsive nano-sponge for oil absorption and desorption. AB - Controlled surface wettability for oil has been intensively studied to remove industrial oil waste or oil spill pollution from seas or rivers. In particular, external stimuli-induced special wetting materials, such as photo-responsive TiO2, have attracted considerable attention for oil-water separation. In this study, a novel method is reported to fabricate a nano-sponge which is composed of hydrophobic hydrocarbon and hydrophilic TiO2 nanoparticles for oil absorption or desorption that are responsive to UV irradiation. The hydrocarbon in the nano sponge could selectively absorb oil from water, whereas the absorbed oil is released into the water by TiO2 in response to UV irradiation. The nano-sponge functionalized porous polydimethylsiloxane released more than 98% of the absorbed crude oil with UV irradiation and air-bubbling. It could be continuously reused while maintaining a high absorption capacity and desorption efficiency without incurring secondary air or water pollution. This smart oil absorption/desorption methodology with excellent selectivity and recyclability with almost perfect removal of absorbed oil can be applied for oil-water separation, oil spill cleanup and reuse of spilled oil. PMID- 26260471 TI - Methodological approach and tools for systems thinking in health systems research: technical assistants' support of health administration reform in the Democratic Republic of Congo as an application. AB - In the field of development cooperation, interest in systems thinking and complex systems theories as a methodological approach is increasingly recognised. And so it is in health systems research, which informs health development aid interventions. However, practical applications remain scarce to date. The objective of this article is to contribute to the body of knowledge by presenting the tools inspired by systems thinking and complexity theories and methodological lessons learned from their application. These tools were used in a case study. Detailed results of this study are in process for publication in additional articles. Applying a complexity 'lens', the subject of the case study is the role of long-term international technical assistance in supporting health administration reform at the provincial level in the Democratic Republic of Congo. The Methods section presents the guiding principles of systems thinking and complex systems, their relevance and implication for the subject under study, and the existing tools associated with those theories which inspired us in the design of the data collection and analysis process. The tools and their application processes are presented in the results section, and followed in the discussion section by the critical analysis of their innovative potential and emergent challenges. The overall methodology provides a coherent whole, each tool bringing a different and complementary perspective on the system. PMID- 26260472 TI - Cooking, storage, and reheating effect on the formation of cholesterol oxidation products in processed meat products. AB - BACKGROUND: Cholesterol is an important biological compound; however, its oxidation products have been proven to be harmful to human health. Cooking, storage, and reheating methods significantly affect the safety of meat products, as they contribute to the production of cholesterol oxidation products (COPs). METHODS: Three cooking methods were used to cook sausages, loin ham, bacon, luncheon meat, and pressed ham, in order to investigate the effect of cooking, storage, and reheating on total cholesterol and on the formation of COPs. Cooked samples were stored at 4 degrees C and reheated after 3 and 6 storage days by the same cooking method or by microwaving. The samples were assessed for total lipids, cholesterol, and cholesterol oxides. RESULTS: The average cholesterol content in the processed meat varied from 76.0 mg/100 g to 201.70 mg/100 g. Microwaved ham showed the lowest cholesterol content compared to that of other processed meat products. Significant differences were found in cholesterol content and cholesterol oxidation products depending on cooking, storage, and reheating methods. Six cholesterol oxides were found in processed meat, of which 7beta-hydroxycholesterol and alpha-epoxides were detected as the major oxidation products. CONCLUSIONS: Microwaving and oven grilling resulted in higher production of COPs in processed meat as compared with other cooking methods. Refrigerated storage tended to significantly increase the COPs content. PMID- 26260473 TI - A 72-hour high fat diet increases transcript levels of the neuropeptide galanin in the dorsal hippocampus of the rat. AB - BACKGROUND: Recent evidence identifies the hippocampus, a brain structure commonly associated with learning and memory, as key to the regulation of food intake and the development and consequences of obesity. Intake of a high fat diet (HFD) results in altered consumptive behavior, hippocampal damage, and cognitive deficits. While many studies report the effects of HFD after chronic consumption and in the instance of obesity, few examine the events that occur following acute HFD consumption. In this study, male rats were fed either a control diet (10% fat by kcal) or HFD (45% fat by kcal) for 72 h. At the end of the 72-h period, serum and tissues were collected and weighed. Brains were rapidly frozen or formalin fixed in preparation for qRT-PCR or immunohistochemistry, respectively. RESULTS: Acute intake of HFD resulted in higher serum levels of leptin and cholesterol, with no significant changes in final body weight or adipose tissue mass. In the dorsal hippocampus, transcription of the neuroprotective peptide galanin was significantly upregulated along with a trend for an increase in brain-derived neurotrophic factor and histone deacetylase 2 in the rats fed HFD. In the ventral hippocampus, there was a significant increase in histone deacetylase 4 and a decrease in galanin receptor 1 in this group. Results from immunohistochemistry validate strong presence of the galanin peptide in the CA1/CA2 region of the dorsal hippocampus. CONCLUSIONS: These results provide evidence for a distinct response in specific functional regions of the hippocampus following acute HFD intake. PMID- 26260475 TI - Erratum to: Nutritional vitamin D supplementation and health-related outcomes in hemodialysis patients: a protocol for a systematic review and meta-analysis. PMID- 26260474 TI - Associations between neighbourhood walkability and daily steps in adults: a systematic review and meta-analysis. AB - BACKGROUND: Higher street connectivity, land use mix and residential density (collectively referred to as neighbourhood walkability) have been linked to higher levels of walking. The objective of our study was to summarize the current body of knowledge on the association between neighbourhood walkability and biosensor-assessed daily steps in adults. METHODS: We conducted a systematic search of PubMed, SCOPUS, and Embase (Ovid) for articles published prior to May 2014 on the association between walkability (based on Geographic Information Systems-derived street connectivity, land use mix, and/or residential density) and daily steps (pedometer or accelerometer-assessed) in adults. The mean differences in daily steps between adults living in high versus low walkable neighbourhoods were pooled across studies using a Bayesian hierarchical model. RESULTS: The search strategy yielded 8,744 unique abstracts. Thirty of these underwent full article review of which six met the inclusion criteria. Four of these studies were conducted in Europe and two were conducted in Asia. A meta analysis of four of these six studies indicates that participants living in high compared to low walkable neighbourhoods accumulate 766 more steps per day (95 % credible interval 250, 1271). This accounts for approximately 8 % of recommended daily steps. CONCLUSIONS: The results of European and Asian studies support the hypothesis that higher neighbourhood walkability is associated with higher levels of biosensor-assessed walking in adults. More studies on this association are needed in North America. PMID- 26260477 TI - Post-traumatic pancreatic pseudocyst managed by Roux-en-Y drainage. AB - A pancreatic pseudocyst is a collection of serous fluid in relation to the pancreas following acute pancreatitis. If pancreatography is performed, most pseudocysts will be found to have a connection with the pancreatic ductal system. Most will resolve spontaneously but clinically significant pseudocysts (~5%) may require surgical intervention. Surgical (laparoscopic or open) direct drainage of pancreatic pseudocysts into the upper gastrointestinal tract is the mainstay of treatment with the possibility of pancreatic resection if malignancy is suspected. We report a persistent post-traumatic pancreatic pseudocyst of 8-year duration, despite recurrent percutaneous aspiration that was finally managed by a Roux-en-Y drainage. PMID- 26260476 TI - Development and evaluation of a SYBR Green real-time RT-PCR assay for detection of avian hepatitis E virus. AB - BACKGROUND: Avian hepatitis E virus (HEV) is the main causative agent of big liver and spleen disease, as well as hepatitis-splenomegaly syndrome in chickens. To date, conventional reverse transcriptase polymerase chain reaction (RT-PCR) and nested RT-PCR methods have been used for the diagnosis of avian HEV infection in chickens. However, these assays are time consuming, inconvenient, and cannot detect the virus quantitatively. In this study, a rapid and sensitive SYBR Green real-time RT-PCR assay was developed to detect avian HEV RNA quantitatively in serum, liver, spleen, and fecal samples from chickens. RESULTS: Based on the sequence of the most conserved HEV gene, ORF3, the primers for the assay were designed, and the standard plasmid was constructed. The detection limit of the assay was shown to be 10 copies/MUl of standard plasmid/reaction, with a corresponding cycle-threshold value of 29.3. The standard curve exhibited a dynamic linear range across at least 7 log units of DNA copy number. The specificity and reproducibility of this assay was high, showing that the assay detected avian HEV RNA specifically and with little variability. Compared to conventional RT-PCR, the current assay is more sensitive for detecting avian HEV in serum, liver, spleen, and fecal samples from chickens. CONCLUSIONS: A rapid, specific, and reproducible SYBR Green real-time RT-PCR assay was developed for the diagnosis of avian HEV infection in chickens. This assay can accurately detect avian HEV RNA in serum, liver, spleen, and fecal samples with more sensitivity than conventional RT-PCR. PMID- 26260478 TI - Clinical relevance of morphologic MRI criteria for the assessment of lymph nodes in patients with rectal cancer. AB - AIM: The aim of this study is the evaluation of lymph node staging by magnetic resonance imaging (MRI) within clinical routine in patients with rectal cancer. METHOD: Routine MRI reports (3 T) of 65 consecutive patients with rectal cancer were retrospectively categorized in lymph node tumor positive or negative (mriN+; mriN0) and compared to the final histopathological results (pN+; pN0). Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy were calculated. The original MRI readings were then reanalyzed in order to identify the longest short-axis lymph node diameter for each patient. A receiver operating characteristic (ROC) curve was used to calculate a possible cutoff value for the short-axis lymph node diameter. RESULTS: Overall sensitivity was 94 %, specificity 13 %, NPV 86 %, PPV 28 %, and accuracy 34 %. The best accuracy could be calculated for a short-diameter cutoff of <=5 mm (83 %); pN+ and pN0 groups were then significantly different (p < 0.0001). CONCLUSION: In clinical routine, lymph node assessment in patients with rectal cancer through MRI tends to overstage malignant lymphadenopathy. A <=5-mm cutoff value for the short-axis lymph node diameter of benign nodes is able to improve the accuracy and has potential to lower the risk of overstaging. PMID- 26260479 TI - Perianal Paget's disease: three decades experience of a single institution. AB - PURPOSE: Perianal Paget's disease is a rare intraepithelial adenocarcinoma of the perianal skin and the second most common localization of extramammary Paget's disease. This study was designed to evaluate long-term outcomes in patients with perianal Paget's disease. METHODS: We identified patients who were treated for perianal Paget's disease between 1981 and 2013. Patient demographics, family history, associated malignancies, treatments, histopathological features, need for re-operations, and long-term outcomes were documented. RESULTS: Our study cohort consisted of 15 male and 10 female patients with a median age of 67 (40 83) years. Four patients had concurrent anorectal adenocarcinoma (two anal canal, two rectal) when perianal Paget's disease was diagnosed. Index operations performed were wide local excision (14 patients), local excision (five patients), abdominoperineal resection (four patients), and radiotherapy (two patients). Five patients developed invasive carcinoma (three anal canal, one vulvar, one perianal squamous cell carcinoma) during a median follow-up time of 60 (3-299) months. Thirteen patients were re-operated. Fifteen patients had a reconstructive procedure following excision. Overall survival was similar between the patients who were treated with wide local excision and local excision regardless of surgical margin status at index excision (P = 0.75). CONCLUSIONS: Since there is a risk for developing invasive carcinoma in the anal canal and perineum in patients with perianal Paget's disease, close follow-up is needed after R0 or R1 excision. Physicians should be aware of the risk of cancers associated with perianal Paget's disease and should rule out them during management. PMID- 26260480 TI - Influence of gentamicin-coded PVDF suture material on the healing of intestinal anastomosis in a rat model. AB - PURPOSE: Intestinal anastomosis is a fundamental procedure in general surgery and required to restore intestinal continuity following resection. The aim of this study was to evaluate whether a gentamicin-coated polyvinylidene fluoride (PVDF) suture material has beneficial effect on anastomotic healing. METHODS: Ninety Sprague-Dawley rats were divided into three groups: a PVDF-suture group, a gentamicin-coated PVDF (GPVDF)-suture group and a control group using Maxon(r) (polyglycolid-co-trimethylene carbonate). For each animal, a colonic anastomosis was performed. Ten animals from each group were sacrificed on postoperative days 3, 5, and 14. Measurements of anastomotic bursting pressure were performed on days 3 and 5. At each time, collagen type I/III ratio, MMP 2 and MMP-9 expression and the proliferation index (Ki67) were analyzed. RESULTS: In total, 90 animals underwent surgery without postoperative complications. Bursting strength in the GPVDF group was significantly elevated on day 5. Immunohistochemistry showed significant increase of the collagen type I/III ratio for PVDF and GPVDF on days 3 and 5. MMP2 was significantly increased for PVDF on days 3 and 5 and for GPVDF on day 5. The analysis of MMP9 revealed significant increase compared to control on day 3 and 5 (GPVDF) as well as on day 5 (PVDF). Staining for Ki67 revealed a significant elevation on postoperative day 3 for the PVDF and the GPVDF group. CONCLUSIONS: The present data shows the feasibility of PVDF as suture material for colonic anastomosis and confirms the ability of gentamicin to increase the stability of colonic anastomosis when used as coating material. PMID- 26260481 TI - The size of retrieved lymph nodes correlates with the number of retrieved lymph nodes and is an independent prognostic factor in patients with stage II colon cancer. AB - PURPOSE: In stage II colon cancer, patients with many retrieved lymph nodes (LNs) have been reported to have better oncological outcomes. We tested the hypothesis that the greater number of retrieved LNs is related to a larger LN size. METHODS: The subjects comprised 320 patients with stage II colon cancer who underwent curative resection. All operations were elective and were performed by the same surgeons. The maximum long axis and short axis diameters of LNs were measured on hematoxylin-eosin-stained specimens. RESULTS: A total of 4,744 LNs were evaluated. The number of retrieved LNs was 14.8 +/- 10.1 (mean +/- SD). The long axis diameter was 4.8 +/- 2.6 mm, with a median value of 4.3 mm, a maximum value of 20.4 mm, and a minimum value of 0.6 mm. The corresponding short axis diameters were 3.4 +/- 1.7, 3.0, 15.1, and 0.5 mm, respectively. The highest correlation coefficient for the association with the number of LNs was obtained for the maximum value of the long axis diameter (0.59). Multivariate analysis revealed that age, tumor location, pathological T stage, and the maximum long axis diameter were independent prognostic factors. The number of LNs was not a significant factor. Patients with less than 12 LNs and a maximum long axis diameter of less than 10 mm had significantly poorer outcomes (p < 0.001). CONCLUSION: In patients with stage II colon cancer, the maximum long axis diameter of LNs correlated with the number of LNs and was an independent prognostic factor. PMID- 26260482 TI - The types of anastomotic leakage that develop following anterior resection for rectal cancer demonstrate distinct characteristics and oncologic outcomes. AB - PURPOSE: The types of anastomotic leakage that develop following rectal cancer surgery and their impact on long-term outcomes are not well documented. This study aimed to compare the clinical characteristics of various types of anastomotic leakage after anterior resection in rectal cancer patients and evaluate their impact on the long-term oncologic outcomes. METHODS: This study analyzed data obtained from 2510 consecutive patients who underwent anterior resection for rectal cancers. Of these patients, 141 (5.6 %) developed anastomotic leakage. Three types of leakage were categorized according to presentation: generalized peritonitis (type I), localized peritonitis (type II), and fistula or chronic sinus (type III). The clinical characteristics and oncologic outcomes were compared. RESULTS: Type I leakage was the most common (I 44.7 %, n = 63; II 30.5 %, n = 43; III 24.8 %, n = 35). Type III occurred more frequently in women (p = 0.001) and patients with low rectal cancer (p < 0.001). Patients with type II or III leakage more frequently underwent radiation therapy (p < 0.001) and diverting ostomy (p < 0.001). Leakage management differed according to the type of leakage (p < 0.001). The local recurrence-free survival rate was significantly lower in patients with type II and III leakage (p = 0.014). CONCLUSIONS: The clinical characteristics and oncologic results are distinct for each type of anastomotic leakage. Only a type II or III leakage increases the risk of local recurrence. Each type of leakage should thus be considered a different disease entity. PMID- 26260483 TI - Comorbidities and colorectal surgery. PMID- 26260484 TI - p38 phosphorylation in medullary microglia mediates ectopic orofacial inflammatory pain in rats. AB - BACKGROUND: Orofacial inflammatory pain is likely to accompany referred pain in uninflamed orofacial structures. The ectopic pain precludes precise diagnosis and makes treatment problematic, because the underlying mechanism is not well understood. Using the established ectopic orofacial pain model induced by complete Freund's adjuvant (CFA) injection into trapezius muscle, we analyzed the possible role of p38 phosphorylation in activated microglia in ectopic orofacial pain. RESULTS: Mechanical allodynia in the lateral facial skin was induced following trapezius muscle inflammation, which accompanied microglial activation with p38 phosphorylation and hyperexcitability of wide dynamic range (WDR) neurons in the trigeminal spinal subnucleus caudalis (Vc). Intra-cisterna successive administration of a p38 mitogen-activated protein kinase selective inhibitor, SB203580, suppressed microglial activation and its phosphorylation of p38. Moreover, SB203580 administration completely suppressed mechanical allodynia in the lateral facial skin and enhanced WDR neuronal excitability in Vc. Microglial interleukin-1beta over-expression in Vc was induced by trapezius muscle inflammation, which was significantly suppressed by SB203580 administration. CONCLUSIONS: These findings indicate that microglia, activated via p38 phosphorylation, play a pivotal role in WDR neuronal hyperexcitability, which accounts for the mechanical hypersensitivity in the lateral facial skin associated with trapezius muscle inflammation. PMID- 26260485 TI - Identification of Differentially Expressed Genes in Chilling-Induced Potato (Solanum tuberosum L.); a Data Analysis Study. AB - Cold stress, as chilling (<20 degrees C) or freezing (<0 degrees C), is one of the frequently exposed stresses in cultivated plants like potato. Under cold stress, plants differentially modulate their gene expression to develop a cold tolerance/acclimation. In the present study, we aimed to identify the overall gene expression profile of chilling-stressed (+4 degrees C) potato at four time points (4, 8, 12, and 48 h), with a particular emphasis on the genes related with transcription factors (TFs), phytohormones, lipid metabolism, signaling pathway, and photosynthesis. A total of 3504 differentially expressed genes (DEGs) were identified at four time points of chilling-induced potato, of which 1397 were found to be up-regulated while 2107 were down-regulated. Heatmap showed that genes were mainly up-regulated at 4-, 8-, and 12-h time points; however, at 48-h time point, they inclined to down-regulate. Seventy five up-regulated TF genes were identified from 37 different families/groups, including mainly from bHLH, WRKY, CCAAT-binding, HAP3, and bZIP families. Protein kinases and calcium were major signaling molecules in cold-induced signaling pathway. A collaborated regulation of phytohormones was observed in chilling-stressed potato. Lipid metabolisms were regulated in a way, highly probably, to change membrane composition to avoid cold damage and render in signaling. A down-regulated gene expression profile was observed in photosynthesis pathway, probably resulting from chilling-induced reduced enzyme activity or light-triggered ROSs damage. The findings of this study will be a valuable theoretical knowledge in terms of understanding the chilling-induced tolerance mechanisms in cultivated potato plants as well as in other Solanum species. PMID- 26260486 TI - Verbal and nonverbal indicators of quality of communication between care staff and residents in ethnoculturally and linguistically diverse long-term care settings. AB - Linguistic and ethnocultural diversity in long-term residential care is a growing trend in many urban settings. When long-term care staff and residents do not share the same language or ethnocultural background, the quality of their communication and care are jeopardized. There is very little research addressing how staff and residents communicate when they experience a mismatch in their language and ethnocultural backgrounds. Thus, the goals of the present study were to 1) document the verbal and nonverbal behaviours used by staff and residents in diverse interactions, and 2) identify and account for behaviours that either promoted or detracted from positive communication by drawing on principles from 'Communication Accommodation Theory'. Two long-term care facilities in British Columbia Canada were selected due to the diverse linguistic and ethnocultural backgrounds of their staff and residents. Twenty-seven staff and 27 residents consented to being video-recorded during routine activities (e.g., mealtimes, recreational activities). The recorded observations were transcribed, translated, and coded using qualitative descriptive and interpretive analyses. A number of verbal and nonverbal behaviours were identified and interpreted in relation to whether they promoted or detracted from positive communication. The findings point to considering a variety of proactive strategies that staff and administrators could employ to effectively accommodate to language and ethnocultural diversity in long-term care practice. PMID- 26260487 TI - Point of care coagulometry in prehospital emergency care: an observational study. AB - BACKGROUND: Haemostatic impairment can have a crucial impact on the outcome of emergency patients, especially in cases of concomitant antithrombotic drug treatment. In this prospective observational study we used a point of care (POC) coagulometer in a prehospital physician-based emergency medical system in order to test its validity and potential value in the treatment of emergency patients. METHODS: During a study period of 12 months, patients could be included if venous access was mandatory for further treatment. The POC device CoaguChek(r) was used to assess international normalized ratio (INR) after ambulance arrival at the scene. Results were compared with in-hospital central laboratory assessment of INR. The gain of time was analysed as well as the potential value of POC testing through a questionnaire completed by the responsible prehospital emergency physician. RESULTS: A total of 103 patients were included in this study. POC INR results were highly correlated with results of conventional assessment of INR (Bland-Altman-bias: 0.014). Using a cutoff value of INR >1.3, the device's sensitivity to detect coagulopathy was 100 % with a specificity of 98.7 %. The median gain of time was 69 min. Treating emergency physicians considered the value of prehospital POC INR testing 'high' in 9 % and 'medium' in 21 % of all patients. In patients with tracer diagnosis 'neurology', the value of prehospital INR assessment was considered 'high' or 'medium' (63 %) significantly more often than in patients with non-neurological tracer diagnoses (24 %). CONCLUSIONS: Assessment of INR through a POC coagulometer is feasible in prehospital emergency care and provides valuable information on haemostatic parameters in patients. Questionnaire results suggest that POC INR testing may present a valuable technique in selected patients. Whether this information translates into an improved management of respective patients has to be evaluated in further studies. PMID- 26260488 TI - Heart rate variability in horses with acute gastrointestinal disease requiring exploratory laparotomy. AB - OBJECTIVE: To describe heart rate variability (HRV) in horses with acute gastrointestinal disease that undergo exploratory laparotomy. We hypothesized that horses with ischemic gastrointestinal disease will have reduced HRV compared to horses with nonischemic lesions. We further hypothesized that a reduction in HRV will be associated with nonsurvival. DESIGN: Prospective, clinical, observational study. SETTING: University veterinary teaching hospital. ANIMALS: Horses presented for acute colic (n = 57) or elective surgical procedures (n = 10) were enrolled. INTERVENTIONS: Admission heart rate (HR) was recorded and within 2 hours of recovery from general anesthesia continuous telemetry was placed, monitored and recorded for 48-52 hours postoperatively. Stored electrocardiograms were manually inspected and R-to-R intervals were extracted and uploaded into HRV software for analysis. Time domain and frequency spectral analysis were investigated at Times 1 (2-10 h), 2 (16-24 h), 3 (30-38 h), and 4 (44-52 h) postoperatively. A two-way ANOVA for repeated measures was used for group comparisons. Logistic regression analysis was used to detect potential associations between admission HR, time and frequency domain variables, and nonsurvival. MEASUREMENTS AND MAIN RESULTS: Horses diagnosed with an ischemic gastrointestinal lesion (n = 22) at the time of surgery had significantly higher postoperative heart rates and reduced time domain-derived measures of HRV than horses with nonischemic gastrointestinal lesions (n = 35) or control horses (n = 10). Horses that survived to discharge had significantly lower postoperative HRs, higher time domain, and lower low frequency spectral measures of HRV compared to nonsurvivors. The multivariable logistic regression model had a receiver operating characteristic area under the curve (AUC) of 0.95 and was significantly better at predicting nonsurvival than admission HR (P = 0.0124). CONCLUSIONS: Reduced HRV was strongly associated with ischemic gastrointestinal disease and nonsurvival. HRV analysis is a noninvasive technique that may provide diagnostic and prognostic information pertinent to the management of postoperative horses with severe gastrointestinal disease. PMID- 26260489 TI - Surgery for chronic inguinodynia following routine herniorrhaphy: beneficial effects on dysejaculation. AB - PURPOSE: Pain during sexual activities and ejaculation is reported by 3-4% of men after routine inguinal herniorrhaphy. The potential beneficial effects of surgery for chronic groin pain on dysejaculation are unknown. The objective of this study was to determine dysejaculation rates in a series of patients reporting chronic postherniorrhaphy pain and evaluate the effects of tailored neurectomy on dysejaculation. METHODS: We evaluated male patients (>18 years) operated for chronic groin pain after inguinal herniorrhaphy during a 6-year time period (2004 2010). Dysejaculation was defined as a burning or searing sensation associated with ejaculation. Men reporting symptoms possibly associated with dysejaculation were sent a questionnaire investigating pain characteristics (VAS, 0-100), influence on sex life and effects of the tailored neurectomy. A Post Herniorrhaphy Dysejaculation Score (PHDS, 0-12 points) was introduced to quantify the severity of the dysejaculation syndrome. RESULTS: A series of 100 males operated for chronic inguinal pain after standard herniorrhaphy were studied. Thirty-four men reported symptoms of dysejaculation prior to the tailored neurectomy. Sex life was negatively influenced in 20 of these, and 5 completely abstained from any sexual activity. Following surgery including tailored neurectomy, funicular release and/or mesh removal, VAS for dysejaculation pain was significantly reduced [n = 20, 55 (95% CI 47-63) versus 21 (95% CI 13-29), p < 0.001]. PHDS scores were also significantly attenuated [n = 20, 10 (3-12) versus 2 (0-10), p < 0.001]. Sex life normalized in two-thirds of these men (13/20). CONCLUSION: Dysejaculation in men suffering from chronic pain after routine inguinal herniorrhaphy is not uncommon. A tailored neurectomy, funicular release and/or mesh removal offer relief in the majority of these patients. PMID- 26260490 TI - Abdominal wall dysfunction in adult bladder exstrophy: a treatable but under recognized problem. AB - PURPOSE: Bladder exstrophy is defined by urogenital and skeletal abnormalities with cosmetic and functional deformity of the lower anterior abdominal wall. The primary management objectives have historically been establishment of urinary continence with renal function preservation, reconstruction of functional and cosmetically acceptable external genitalia, and abdominal wall closure of some variety. The literature has focused on the challenges of neonatal approaches to abdominal wall closure; however, there has been a paucity of long-term followup to identify the presence and severity of abdominal wall defects in adulthood. Our goal was to characterize the adult disease and determine effective therapy. METHODS: A retrospective review of a consecutive series of six patients was performed. RESULTS: We report and characterize the presence of severe abdominal wall dysfunction in these adult exstrophy patients treated as children. We tailored an abdominal wall and pelvic floor reconstruction with long-term success to highlight a need for awareness of the magnitude of the problem and its solvability. CONCLUSIONS: The natural history of abdominal wall laxity and the long-term consequences of cloacal exstrophy closure have gone unexplored and unreported. Evaluation of our series facilitates understanding in this complex area and may be valuable for patients who are living limited lives thinking that no solution is available. PMID- 26260491 TI - The PROMIS of QALYs. AB - Measuring health and health-related quality of life (HRQoL) is important for tracking the health of individuals and populations over time. Generic HRQoL measures allow for comparison across health conditions. One form of generic HRQoL measures are profile measures, which provide a description of health across several different domains (such as physical functioning, depression, and pain). Recent advances in health profile measurement include the development of measures based on item response theory. The Patient-Reported Outcomes Measurement Information System (PROMIS(r)) has been constructed using this theory. Another form of generic HRQoL measures are utility measures, which assess the value of health states. Multi-attribute utility theory provides a framework for valuing disparate domains of health and aggregating them into a single preference-based score. Such a score provides an overall measure of health outcomes as well as a quality of life weight for use in decision analyses and cost-effectiveness analyses. Developing a utility score for PROMIS(r) would allow simultaneous estimation of both health profile and utility scores using a single measure. The purpose of this paper is to provide a roadmap of the methodological steps necessary to create such a scoring system. PMID- 26260492 TI - Total Worker Health Intervention Increases Activity of Sedentary Workers. AB - INTRODUCTION: Office employees are exposed to hazardous levels of sedentary work. Interventions that integrate health promotion and health protection elements are needed to advance the health of sedentary workers. This study tested an integrated intervention on occupational sedentary/physical activity behaviors, cardiometabolic disease biomarkers, musculoskeletal discomfort, and work productivity. DESIGN: Two-group, RCT. Data were collected between January and August 2014. SETTING/PARTICIPANTS: Overweight/obese adults working in sedentary desk jobs were randomized to: (1) a health protection-only group (HPO, n=27); or (2) an integrated health protection/health promotion group (HP/HP, n=27). INTERVENTION: HPO participants received an ergonomic workstation optimization intervention and three e-mails/week promoting rest breaks and posture variation. HP/HP participants received the HPO intervention plus access to a seated activity permissive workstation. MAIN OUTCOME MEASURES: Occupational sedentary and physical activity behaviors (primary outcomes), cardiometabolic health outcomes, musculoskeletal discomfort, and work productivity (secondary outcomes) were measured at baseline and post-intervention (16 weeks). RESULTS: The HP/HP group increased occupational light intensity physical activity over the HPO group and used the activity permissive workstations 50 minutes/work day. Significant associations were observed between activity permissive workstation adherence and improvements in several cardiometabolic biomarkers (weight, total fat mass, resting heart rate, body fat percentage) and work productivity outcomes (concentration at work, days missed because of health problems). CONCLUSIONS: The HP/HP group increased occupational physical activity and greater activity permissive workstation adherence was associated with improved health and work productivity outcomes. These findings are important for employers interested in advancing the well-being of sedentary office workers. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov NCT02071420. PMID- 26260493 TI - Brain connectomics predict response to treatment in social anxiety disorder. AB - We asked whether brain connectomics can predict response to treatment for a neuropsychiatric disorder better than conventional clinical measures. Pre treatment resting-state brain functional connectivity and diffusion-weighted structural connectivity were measured in 38 patients with social anxiety disorder (SAD) to predict subsequent treatment response to cognitive behavioral therapy (CBT). We used a priori bilateral anatomical amygdala seed-driven resting connectivity and probabilistic tractography of the right inferior longitudinal fasciculus together with a data-driven multivoxel pattern analysis of whole-brain resting-state connectivity before treatment to predict improvement in social anxiety after CBT. Each connectomic measure improved the prediction of individuals' treatment outcomes significantly better than a clinical measure of initial severity, and combining the multimodal connectomics yielded a fivefold improvement in predicting treatment response. Generalization of the findings was supported by leave-one-out cross-validation. After dividing patients into better or worse responders, logistic regression of connectomic predictors and initial severity combined with leave-one-out cross-validation yielded a categorical prediction of clinical improvement with 81% accuracy, 84% sensitivity and 78% specificity. Connectomics of the human brain, measured by widely available imaging methods, may provide brain-based biomarkers (neuromarkers) supporting precision medicine that better guide patients with neuropsychiatric diseases to optimal available treatments, and thus translate basic neuroimaging into medical practice. PMID- 26260494 TI - Disruption of mGluR5 in parvalbumin-positive interneurons induces core features of neurodevelopmental disorders. AB - Alterations in glutamatergic transmission onto developing GABAergic systems, in particular onto parvalbumin-positive (Pv(+)) fast-spiking interneurons, have been proposed as underlying causes of several neurodevelopmental disorders, including schizophrenia and autism. Excitatory glutamatergic transmission, through ionotropic and metabotropic glutamate receptors, is necessary for the correct postnatal development of the Pv(+) GABAergic network. We generated mutant mice in which the metabotropic glutamate receptor 5 (mGluR5) was specifically ablated from Pv(+) interneurons postnatally, and investigated the consequences of such a manipulation at the cellular, network and systems levels. Deletion of mGluR5 from Pv(+) interneurons resulted in reduced numbers of Pv(+) neurons and decreased inhibitory currents, as well as alterations in event-related potentials and brain oscillatory activity. These cellular and sensory changes translated into domain specific memory deficits and increased compulsive-like behaviors, abnormal sensorimotor gating and altered responsiveness to stimulant agents. Our findings suggest a fundamental role for mGluR5 in the development of Pv(+) neurons and show that alterations in this system can produce broad-spectrum alterations in brain network activity and behavior that are relevant to neurodevelopmental disorders. PMID- 26260495 TI - Infant mortality and causes of infant deaths in rural Ethiopia: a population based cohort of 3684 births. AB - BACKGROUND: Ethiopia has made large-scale healthcare investments to improve child health and survival. However, there is insufficient population level data on the current estimates of infant mortality rate (IMR) in the country. The aim of this study was to measure infant mortality rate, investigate risk factors for infant deaths and identify causes of death in a rural population of northern Ethiopia. METHODS: Live births to a cohort of mothers under the Kilite Awlaelo Health and Demographic Surveillance System were followed up to their first birthday or death, between September 11, 2009 and September 10, 2013. Maternal and infant characteristics were collected at baseline and during the regular follow-up visit. Multiple-Cox regression was used to investigate risk factors for infant death. Causes of infant death were identified using physician review verbal autopsy method. RESULTS: Of the total 3684 infants followed, 174 of them died before their first birthday, yielding an IMR of 47 per 1000 live births (95 % CI: 41, 54) over the four years of follow-up. About 96 % of infants survived up to their first birthday, and 56 % of infant deaths occurred during the neonatal period. Infants born to mothers aged 15-19 years old had higher risk of death (HR = 2.68, 95 % CI: 1. 74, 4.87) than those born to 25-29 years old. Infants of mothers who attained a secondary school and above had 56 % lower risk of death (HR = 0.44, 95 % CI: 0.24, 0.81) compared to those whose mothers did not attend formal education. Sepsis, prematurity and asphyxia and acute lower respiratory tract infections were the commonest causes of death. CONCLUSION: The IMR for the four-year period was lower than the national and regional estimates. Our findings suggest the need to improve the newborn care, and empower teenagers to delay teenage pregnancy and attain higher levels of education. PMID- 26260496 TI - The immune response in the CNS in Theiler's virus induced demyelinating disease switches from an early adaptive response to a chronic innate-like response. AB - Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) is an important model of the progressive disability caused by irreversible CNS tissue injury, and provides an example of how a CNS pathogen can cause inflammation, demyelination, and neuronal damage. We were interested in which molecules, especially inflammatory mediators, might be upregulated in the CNS throughout TMEV-IDD. We quantitated by a real-time RT-PCR multi-gene system the expression of a pathway-focused panel of genes at 30 and 165 days post infection, characterizing both the early inflammatory and the late neurodegenerative stages of TMEV-IDD. Also, we measured 32 cytokines/chemokines by multiplex Luminex analysis in CSF specimens from early and late TMEV-IDD as well as sham-treated mice. Results indicate that, in the later stage of TMEV-IDD, activation of the innate immune response is most prominent: TLRs, type I IFN response genes, and innate immunity-associated cytokines were highly expressed in late TMEV-IDD compared to sham (p <= 0.0001) and early TMEV-IDD (p < 0.05). Conversely, several molecular mediators of adaptive immune response were highly expressed in early TMEV-IDD (all p <= 0.001). Protein detection in the CSF was broadly concordant with mRNA abundance of the corresponding gene measured by real-time RT-PCR in the spinal cord, since several cytokines/chemokines were increased in the CSF of TMEV IDD mice. Results show a clear shift from adaptive to innate immunity from early to late TMEV-IDD, indicating that adaptive and innate immune pathways are likely involved in the development and progression of the disease to different extents. CSF provides an optimal source of biomarkers of CNS neuroinflammation. PMID- 26260497 TI - Association of Interstage Home Monitoring With Mortality, Readmissions, and Weight Gain: A Multicenter Study from the National Pediatric Cardiology Quality Improvement Collaborative. AB - BACKGROUND: Daily home monitoring of oxygen saturation and weight has been reported to improve outcomes for patients with single-ventricle heart disease during the period between stage I palliation and stage II palliation. However, these studies have been limited to single institutions and used historical control subjects. Our objective was to determine the association of various interstage home monitoring strategies with outcomes using a multicenter cohort with contemporary control subjects. METHODS AND RESULTS: We performed a retrospective cohort study using prospectively collected data from the National Pediatric Cardiology Quality Improvement Collaborative from 2008 to 2012. We compared interstage mortality, unscheduled readmissions, and change in weight-for age Z score for various home monitoring strategies of oxygen saturation (n=494) or weight (n=472), adjusting for sex, syndrome, tricuspid regurgitation, arch obstruction, and shunt type. Overall interstage mortality was 8.1%, and 47% had >=1 unscheduled readmission. We did not find any associations of home oxygen saturation or weight monitoring with mortality or readmission. Although there was no difference in weight-for-age Z score for daily (0.33+/-0.12) versus weekly (0.34+/-0.18, P=0.98) weight monitoring, daily home weight monitoring was superior to no home weight monitoring (-0.15+/-0.18; P<0.01). CONCLUSIONS: Home weight monitoring is associated with improved weight gain during the interstage period, but we did not find any benefits in other clinical outcomes for either home oxygen saturation monitoring or home weight monitoring. PMID- 26260498 TI - Mechanical Support for the Failing Right Ventricle in Patients With Precapillary Pulmonary Hypertension. PMID- 26260499 TI - Common Cause of Mortality in Trauma but Manageable Nonetheless. PMID- 26260501 TI - A Heart With Quadruple Atria: Does it Exist? PMID- 26260502 TI - Cardiology Patient Page. Obstructive Sleep Apnea. PMID- 26260503 TI - Letter by Frigerio et al Regarding Article, "Long-Term Outcomes of Inoperable Patients With Aortic Stenosis Randomly Assigned to Transcatheter Aortic Valve Replacement or Standard Therapy". PMID- 26260504 TI - Response to Letter Regarding Article, "Long-Term Outcomes of Inoperable Patients With Aortic Stenosis Randomly Assigned to Transcatheter Aortic Valve Replacement or Standard Therapy". PMID- 26260505 TI - Letter by Muskiet et al Regarding Article, "Heart Failure, Saxagliptin, and Diabetes Mellitus: Observations From the SAVOR-TIMI 53 Randomized Trial". PMID- 26260506 TI - Response to Letter Regarding Article, "Heart Failure, Saxagliptin and Diabetes Mellitus: Observations From the SAVOR-TIMI 53 Randomized Trial". PMID- 26260507 TI - Arrhythmogenic Left Ventricular Cardiomyopathy: Suspected by Cardiac Magnetic Resonance Imaging, Confirmed by Identification of a Novel Plakophilin-2 Variant. PMID- 26260509 TI - Current progress in the biology of members of the Sporothrix schenckii complex following the genomic era. AB - Sporotrichosis has been attributed for more than a century to one single etiological agent, Sporothrix schencki. Only eight years ago, it was described that, in fact, the disease is caused by several pathogenic cryptic species. The present review will focus on recent advances to understand the biology and virulence of epidemiologically relevant pathogenic species of the S. schenckii complex. The main subjects covered are the new clinical and epidemiological aspects including diagnostic and therapeutic challenges, the development of molecular tools, the genome database and the perspectives for study of virulence of emerging Sporothrix species. PMID- 26260508 TI - Canine atopic dermatitis: detailed guidelines for diagnosis and allergen identification. AB - BACKGROUND: Canine atopic dermatitis (AD) is a common, genetically predisposed, inflammatory and pruritic skin disease. The variation in clinical presentations, due to genetic factors, extent of the lesions, stage of the disease, secondary infections, as well as resemblance to other non-atopic related skin diseases, can complicate a diagnosis of canine AD. A sub-group of the International Committee for Allergic Diseases in Animals (ICADA) was tasked with the development of a set of practical guidelines that can be used to assist practitioners and researchers in the diagnosis of canine AD. Online citation databases and abstracts from international meetings were searched for publications related to the topic, and combined with expert opinion where necessary. The final set of guidelines was approved by the entire ICADA committee. RESULTS: A total of 81 publications relevant for this review were identified. The guidelines generated focus on three aspects of the diagnostic approach: 1. Ruling out of other skin conditions with clinical signs resembling, or overlapping with canine AD. 2. Detailed interpretation of the historical and clinical features of patients affected by canine AD. 3. Allergy testing by intradermal versus allergen-specific IgE serum testing. CONCLUSIONS: The diagnosis of canine AD is based on meeting clinical criteria and ruling out other possible causes with similar clinical signs. Flea combing, skin scraping and cytology should be performed, where necessary, as part of a thorough work-up. Elimination diet trials are required for patients with perennial pruritus and/or concurrent gastrointestinal signs. Once a clinical diagnosis of canine AD is made, allergy testing can be performed to identify potential causative allergens for allergen-specific immunotherapy. PMID- 26260510 TI - A link between Sas2-mediated H4 K16 acetylation, chromatin assembly in S-phase by CAF-I and Asf1, and nucleosome assembly by Spt6 during transcription. AB - The histone acetyltransferase Sas2 is part of the SAS-I complex and acetylates lysine 16 of histone H4 (H4 K16Ac) in the genome of Saccharomyces cerevisiae. Sas2-mediated H4 K16Ac is strongest over the coding region of genes with low expression. However, it is unclear how Sas2-mediated acetylation is incorporated into chromatin. Our previous work has shown physical interactions of SAS-I with the histone chaperones CAF-I and Asf1, suggesting a link between SAS-I-mediated acetylation and chromatin assembly. Here, we find that Sas2-dependent H4 K16Ac in bulk histones requires passage of the cells through the S-phase of the cell cycle, and the rate of increase in H4 K16Ac depends on both CAF-I and Asf1, whereas steady-state levels and genome-wide distribution of H4 K16Ac show only mild changes in their absence. Furthermore, H4 K16Ac is deposited in chromatin at genes upon repression, and this deposition requires the histone chaperone Spt6, but not CAF-I, Asf1, HIR or Rtt106. Altogether, our data indicate that Spt6 controls H4 K16Ac levels by incorporating K16-unacetylated H4 in strongly transcribed genes. Upon repression, Spt6 association is decreased, resulting in less deposition of K16-unacetylated H4 and therefore in a concomitant increase of H4 K16Ac that is recycled during transcription. PMID- 26260511 TI - An ethnomedicinal study of the Seri people; a group of hunter-gatherers and fishers native to the Sonoran Desert. AB - BACKGROUND: Worldwide, coastal communities' ethnomedicinal knowledge has been sporadically recorded and poorly understood. Based on the ethnomedicinal knowledge of the Seri people; a hunting-gathering and fishing society of Northwestern Mexico, this study assesses a) the biological richness of Seri ethnomedicinal knowledge, b) the fidelity level of Seri remedies, and c) the association between gender, age, years of formal schooling and Seri ethnomedicinal knowledge. METHODS: To assess the degree of ethnomedicinal knowledge proficiency, we conducted 75 open-ended semi-structured interviews collecting information on ethnomedicinal knowledge of marine and terrestrial organisms and the socio-demographic profile of each collaborator. With the support of primary collaborators, we collected the materials to be used as stimuli along our interviews. A correlation analysis was used to determine the relationship between gender, literacy and age with the ethnomedicinal knowledge proficiency. A paired t-test was used to determine differences in the number of remedies known by gender among members of the Seri community. RESULTS: A total of 28 medicinal specimens were presented as stimuli material. Marine remedies (12 species), were represented by 4 algae, 3 mollusks, 3 echinoderms, on reptile, and one annelid. Terrestrial plants (13 species) were distributed in 12 families. About 40 % of marine preparations used the organism in whole. In contrast, 29 % of of the remedies involving plants made use of leafy branches. Stimuli materials are used against 17 ailments mainly, being diarrhea, colds, menstrual problems, and swelling the ailments against most organisms (44 %) are used for. Marine organisms presented higher fidelity level values overall, suggesting that lower fidelity levels in terrestrial plants reflect a process of continuous and ongoing experimentation with easily accessible biological materials. Highest fidelity level values were recorded for Atriplex barclayana (93.87 %) Batis maritima (84.37 %), and Turbo fluctuosus (84.21 %). Age moderately correlates to ethnomedicinal knowledge proficiency (r = 0.41). Conversely, years of formal schooling show a negative correlation with ethnomedicinal knowledge proficiency (r = -0.49). Significant differences (p <0.05) were observed on ethnomedicinal knowledge proficiency when gender groups were compared under a paired t-test. CONCLUSIONS: This research contributes to describing the complex biodiversity present in the ethnomedicinal systems of coastal non-agricultural societies. In addition, our research improves our understanding of the role that gender plays in the intra-cultural distribution of ethnomedicinal knowledge among Seri. Our results broaden our understanding of human adaptations to coastal and xeric environments. This research can potentially benefit the development of proposals to improve coastal and marine resource management and conservation while strengthening ethnomedicinal knowledge systems in populations, such as the Seri, limited by precarious socio-economic conditions and inadequate health services. PMID- 26260512 TI - Interstitial Outburst of Angiogenic Factors During Skeletal Muscle Regeneration After Acute Mechanical Trauma. AB - Angiogenesis is a key event during tissue regeneration, but the intimate mechanisms controlling this process are still largely unclear. Therefore, the cellular and molecular interplay along normal tissue regeneration should be carefully unveiled. To this matter, we investigated by xMAP assay the dynamics of some angiogenic factors known to be involved in tissue repair, such as follistatin (FST), Placental Growth Factor-2 (PLGF-2), epidermal growth factor (EGF), betacellulin (BTC), and amphiregulin (AREG) using an animal model that mimics acute muscle contusion injuries. In situ immunofluorescence was used for the evaluation and tissue distribution of their cellular sources. Tissue levels of explored factors increased significantly during degeneration and inflammatory stage of regeneration, peaking first week postinjury. However, except for PLGF-2 and EGF, their levels remained significantly elevated after the inflammatory process started to fade. Serum levels were significantly increased only after 24 h for AREG and EGF. Though, for all factors except FST, the levels in injured samples did not correlate with serum or contralateral tissue levels, excluding the systemic influence. We found significant correlations between the levels of EGF and AREG, BTC, FST and FST and AREG in injured samples. Interstitial cells expressing these factors were highlighted by in situ immunolabeling and their number correlated with measured levels dynamics. Our study provides evidence of a dynamic level variation along the regeneration process and a potential interplay between selected angiogenic factors. They are synthesized, at least partially, by cell populations residing in skeletal muscle interstitium during regeneration after acute muscle trauma. PMID- 26260513 TI - Critical Roles of the LIM Domains of Lhx3 in Recruiting Coactivators to the Motor Neuron-Specifying Isl1-Lhx3 Complex. AB - During spinal cord development, the LIM domains of the LIM homeodomain factor Lhx3 bind to either the LIM cofactor nuclear LIM interactor (NLI) or another LIM homeodomain factor, Isl1, assembling the tetrameric V2 interneuron-specifying Lhx3 complex (2NLI:2Lhx3) or the hexameric motor neuron-specifying Isl1-Lhx3 complex (2NLI:2Isl1:2Lhx3). However, the detailed molecular basis by which the Lhx3-LIM domains contribute to motor neuron specification still remains poorly understood. Here, we show that the Lhx3-LIM domains are essential for recruiting transcriptional coactivators to the Isl1-Lhx3 complex. Using a yeast genetic screening system, we identify Lhx3 point mutants that bind to NLI but not Isl1. Accordingly, these mutants fail to assemble the Isl1-Lhx3 complex. However, their interaction with coactivators is relatively intact, and they are fully functional in the Lhx3 complex and V2 interneuron specification. Interestingly, when these Lhx3 mutants are directly fused to Isl1, their transcriptional activity in the Isl1-Lhx3 complex is restored. We further show that this restoration reflects an unexpected role of the Lhx3-LIM domains, likely together with Isl1, to form an interaction interface for coactivators. Our results suggest that the Lhx3-LIM domains play critical roles in transactivation of the Isl1-Lhx3 complex by not only directing the assembly of the Isl1-Lhx3 complex but also recruiting coactivators to the complex. PMID- 26260514 TI - Standardized multilevel transition program: Does it affect renal transplant outcome? AB - The transfer of renal transplant patients from pediatric to adult care is a crucial step with a high risk of subsequent graft loss. Therefore, the transition should be a thoroughly planned, well-designed and multidisciplinary process focused on the individual patient. Our pediatric nephrology department introduced a structured step-by-step transition program supported by a multidisciplinary team of health professionals. The purpose of our study was to determine the effects of the transition program on eGFR and number of ARs in comparison to a group without a transition program at one and three yr after transfer. We conducted a single-center retrospective cohort study of renal transplant patients prior to and after the introduction of the transition program. Multiple regression analysis revealed a significantly lower decline of eGFR in the group with transition program (-11.3 +/- 44 mL/min/1.73 m(2) ) compared to the group without transition program (-28.4 +/- 33 mL/min/1.73 m(2) ) at three yr after transfer. The number of AR episodes significantly decreased from 34.6% in the group without transition program to 9.1% in the group with transition program. The standardized multilevel transition program seems to have significant positive effects on eGFR and number of AR episodes in renal transplant patients. PMID- 26260517 TI - In vitro study of valve-in-valve performance with the CoreValve self-expandable prosthesis implanted in different positions and sizes within the Trifecta surgical heart valve. PMID- 26260516 TI - The crystal structure of the thiocyanate-forming protein from Thlaspi arvense, a kelch protein involved in glucosinolate breakdown. AB - Kelch repeat-containing proteins are involved in diverse cellular processes, but only a small subset of plant kelch proteins has been functionally characterized. Thiocyanate-forming protein (TFP) from field-penny cress, Thlaspi arvense (Brassicaceae), is a representative of specifier proteins, a group of kelch proteins involved in plant specialized metabolism. As components of the glucosinolate-myrosinase system of the Brassicaceae, specifier proteins determine the profile of bioactive products formed when plant tissue is disrupted and glucosinolates are hydrolyzed by myrosinases. Here, we describe the crystal structure of TaTFP at a resolution of 1.4 A. TaTFP crystallized as homodimer. Each monomer forms a six-blade beta-propeller with a wide "top" and a narrower "bottom" opening with distinct strand-connecting loops protruding far beyond the lower propeller surface. Molecular modeling and mutational analysis identified residues for glucosinolate aglucone and Fe(2+) cofactor binding within these loops. As the first experimentally determined structure of a plant kelch protein, the crystal structure of TaTFP not only enables more detailed mechanistic studies on glucosinolate breakdown product formation, but also provides a new basis for research on the diverse roles and mechanisms of other kelch proteins in plants. PMID- 26260518 TI - Determining the number of stimuli required to reliably assess corticomotor excitability and primary motor cortical representations using transcranial magnetic stimulation (TMS): a protocol for a systematic review and meta-analysis. AB - BACKGROUND: Transcranial magnetic stimulation (TMS) is a technique that can be used to assess corticospinal plasticity. Current TMS practices involve the administration of multiple stimuli over target areas of the participant's scalp. However, these procedures require 1 to 2 h per assessment. Decreasing the number of stimuli delivered during TMS assessments would improve time efficiency and decrease participant demand. Thus, the aim of this review is to determine the number of TMS stimuli required to reliably measure (1) corticomotor excitability to a target muscle at a single cranial site and (2) the topography of the primary motor cortical representation for a target muscle across multiple cranial sites (termed 'mapping'). METHODS/DESIGN: A systematic review and meta-analysis will be conducted. Electronic databases will be searched using pre-determined search terms to identify relevant studies and evaluate the studies for inclusion and risks of bias. Two independent reviewers will extract the data. Any disagreements will be resolved by a third reviewer. Studies employing single-pulse TMS to measure (1) corticomotor excitability at a single cranial site or (2) the topographic cortical organisation of a target muscle across a number of cranial sites, published before May 2015, will be included if they meet the eligibility criteria. Outcomes will include motor-evoked potential amplitude, map volume, number of active map sites, location of the map centre of gravity, and distance between the centres of gravity of the target muscle and one or more neighbouring muscles. DISCUSSION: To our knowledge, this review will be the first to systematically explore the number of TMS stimuli required to reliably measure both corticomotor excitability and the topography of primary motor cortical representations. This research has the capacity to improve the efficiency of TMS, decrease participant demand, and facilitate the use of TMS as an outcome measurement tool in clinical populations. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015024579. PMID- 26260519 TI - Effect of protein supplementation on ruminal parameters and microbial community fingerprint of Nellore steers fed tropical forages. AB - In tropical regions, protein supplementation is a common practice in dairy and beef farming. However, the effect of highly degradable protein in ruminal fermentation and microbial community composition has not yet been investigated in a systematic manner. In this work, we aimed to investigate the impact of casein supplementation on volatile fatty acids (VFA) production, specific activity of deamination (SAD), ammonia concentration and bacterial and archaeal community composition. The experimental design was a 4*4 Latin square balanced for residual effects, with four animals (average initial weight of 280+/-10 kg) and four experimental periods, each with duration of 29 days. The diet comprised Tifton 85 (Cynodon sp.) hay with an average CP content of 9.8%, on a dry matter basis. Animals received basal forage (control) or infusions of pure casein (230 g) administered direct into the rumen, abomasum or divided (50 : 50 ratio) in the rumen/abomasum. There was no differences (P>0.05) in ruminal pH and microbial protein concentration between supplemented v. non-supplemented animals. However, in steers receiving ruminal infusion of casein the SAD and ruminal ammonia concentration increased 33% and 76%, respectively, compared with the control. The total concentration of VFA increased (P0.05) in species richness and diversity of gamma-proteobacteria, firmicutes and archaea between non-supplemented Nellore steers and steers receiving casein supplementation in the rumen. However, species richness and the Shannon-Wiener index were lower (P<0.05) for the phylum bacteroidetes in steers supplemented with casein in the rumen compared with non supplemented animals. Venn diagrams indicated that the number of unique bands varied considerably among individual animals and was usually higher in number for non-supplemented steers compared with supplemented animals. These results add new knowledge about the effects of ruminal and postruminal protein supplementation on metabolic activities of rumen microbes and the composition of bacterial and archaeal communities in the rumen of steers. PMID- 26260520 TI - Lipid binding protein response to a bile acid library: a combined NMR and statistical approach. AB - Primary bile acids, differing in hydroxylation pattern, are synthesized from cholesterol in the liver and, once formed, can undergo extensive enzyme-catalysed glycine/taurine conjugation, giving rise to a complex mixture, the bile acid pool. Composition and concentration of the bile acid pool may be altered in diseases, posing a general question on the response of the carrier (bile acid binding protein) to the binding of ligands with different hydrophobic and steric profiles. A collection of NMR experiments (H/D exchange, HET-SOFAST, ePHOGSY NOESY/ROESY and (15) N relaxation measurements) was thus performed on apo and five different holo proteins, to monitor the binding pocket accessibility and dynamics. The ensemble of obtained data could be rationalized by a statistical approach, based on chemical shift covariance analysis, in terms of residue specific correlations and collective protein response to ligand binding. The results indicate that the same residues are influenced by diverse chemical stresses: ligand binding always induces silencing of motions at the protein portal with a concomitant conformational rearrangement of a network of residues, located at the protein anti-portal region. This network of amino acids, which do not belong to the binding site, forms a contiguous surface, sensing the presence of the bound lipids, with a signalling role in switching protein-membrane interactions on and off. PMID- 26260521 TI - Contrasting effects of chloride on growth, reproduction, and toxicant sensitivity in two genetically distinct strains of Hyalella azteca. AB - The strain of Hyalella azteca (Saussure: Amphipoda) commonly used for aquatic toxicity testing in the United States has been shown to perform poorly in some standardized reconstituted waters frequently used for other test species. In 10-d and 42-d experiments, the growth and reproduction of the US laboratory strain of H. azteca was shown to vary strongly with chloride concentration in the test water, with declining performance observed below 15 mg/L to 20 mg/L. In contrast to the chloride-dependent performance of the US laboratory strain of H. azteca, growth of a genetically distinct strain of H. azteca obtained from an Environment Canada laboratory in Burlington, Ontario, Canada, was not influenced by chloride concentration. In acute toxicity tests with the US laboratory strain of H. azteca, the acute toxicity of sodium nitrate increased with decreasing chloride in a pattern similar not only to that observed for control growth, but also to previous acute toxicity testing with sodium sulfate. Subsequent testing with the Burlington strain showed no significant relationship between chloride concentration and the acute toxicity of sodium nitrate or sodium sulfate. These findings suggest that the chloride-dependent toxicity shown for the US laboratory strain may be an unusual feature of that strain and perhaps not broadly representative of aquatic organisms as a whole. PMID- 26260522 TI - Perceived benefits and challenges of repeated exposure to high fidelity simulation experiences of first degree accelerated bachelor nursing students. AB - This study explored perceptions of first-degree entry-level accelerated bachelor nursing students regarding benefits and challenges of exposure to multiple high fidelity simulation (HFS) scenarios, which has not been studied to date. These perceptions conformed to some research findings among Associate Degree, traditional non-accelerated, and second-degree accelerated Bachelor of Science in Nursing (BSN) students faced with one to two simulations. However, first-degree accelerated BSN students faced with multiple complex simulations perceived improvements on all outcomes, including critical thinking, confidence, competence, and theory-practice integration. On the negative side, some reported feeling overwhelmed by the multiple HFS scenarios. Evidence from this study supports HFS as an effective teaching and learning method for nursing students, along with valuable implications for many other fields. PMID- 26260523 TI - The influences of nursing education on the socialization and professional working relationships of Canadian practical and degree nursing students: A critical analysis. AB - BACKGROUND: Little evidence exists about how education influences the ways that registered nurses (RN) and registered practical nurses (RPN) negotiate their professional work relationships. DESIGN: This qualitative study used interviews and reflective writing from 250 Bachelor of Science in Nursing (BScN) and Practical Nursing (PN) students to explore how education constructs intraprofessional relations. The data were collected after two joint BScN/PN education events - one held in the first semester and one in the fourth semester. RESULTS: The findings reveal how education conveys and establishes dominant discourses about the tiers in nursing and the boundary work and professional closure strategies used by the two groups. In addition, although the two education programs are largely segregated and education about how to work with each other is rarely discussed, PN and BScN students strive to understand the differences and perceived inequities between the two designations of nurse. The data show how students attempt to reconcile the tensions and disjunctures they experience from the power relations by activating socially constructed and hegemonic positions that have been problematic for nursing. CONCLUSION: Findings will assist nurse educators to understand how education can be used to negotiate professional boundaries and working relationships that foster equity and social inclusion. PMID- 26260524 TI - High fidelity patient simulation as an educational tool in paediatric intensive care: A systematic review. AB - OBJECTIVE: The aim of this study was to examine the use of high fidelity patient simulation (HFPS) in paediatric intensive care nursing education through the use of a systematic literature review. METHOD: A systematic search was undertaken in the electronic databases CINAHL (via EBSCOhost), Medline and Pubmed, ClinicalKey, Science Direct and OVID. Electronic searches were supplemented by hand searches of journals, individual article reference lists and the World Wide Web. Main outcome measures were learner outcomes. The search was limited to papers published in English between 2000 and 2015. RESULTS: Eight papers satisfied the inclusion criteria of the review. Studies included in the review ranged from moderate to low on the quality assessment scale. HFPS training was associated with improved short-term learner outcomes of various measures, however this should be considered with the small number of studies examining this topic and the scarcity of high quality randomised studies. CONCLUSIONS: The evidence of improved learner outcomes following HFPS training in paediatric intensive care (PICU) nursing education should be considered together with the quality and methodological limitations of existing research. There was no evidence of negative effects. The direction of research suggests that HFPS is a useful tool in the education of PICU nurses. PMID- 26260525 TI - Recurrent CD4-/CD8- peripheral T-cell lymphoma with change in cytoarchitectural features and immunophenotype over the course of disease. PMID- 26260526 TI - 151 years Berliner Klinische Wochenschrift and the 20th anniversary of the Journal of Molecular Medicine. PMID- 26260527 TI - Genome-Wide Identification and Characterization of Novel Factors Conferring Resistance to Topoisomerase II Poisons in Cancer. AB - The topoisomerase II poisons doxorubicin and etoposide constitute longstanding cornerstones of chemotherapy. Despite their extensive clinical use, many patients do not respond to these drugs. Using a genome-wide gene knockout approach, we identified Keap1, the SWI/SNF complex, and C9orf82 (CAAP1) as independent factors capable of driving drug resistance through diverse molecular mechanisms, all converging on the DNA double-strand break (DSB) and repair pathway. Loss of Keap1 or the SWI/SNF complex inhibits generation of DSB by attenuating expression and activity of topoisomerase IIalpha, respectively, whereas deletion of C9orf82 augments subsequent DSB repair. Their corresponding genes, frequently mutated or deleted in human tumors, may impact drug sensitivity, as exemplified by triple negative breast cancer patients with diminished SWI/SNF core member expression who exhibit reduced responsiveness to chemotherapy regimens containing doxorubicin. Collectively, our work identifies genes that may predict the response of cancer patients to the broadly used topoisomerase II poisons and defines alternative pathways that could be therapeutically exploited in treatment resistant patients. PMID- 26260528 TI - Inferring the Origin of Metastases from Cancer Phylogenies. AB - Determining the evolutionary history of metastases is a key problem in cancer biology. Several recent studies have presented inferences regarding the origin of metastases based on phylogenies of cancer lineages. Many of these studies have concluded that the observed monophyly of metastatic subclones favored metastasis to-metastasis spread ("a metastatic cascade" rather than parallel metastases from the primary tumor). In this article, we argue that identifying a monophyletic clade of metastatic subclones does not provide sufficient evidence to unequivocally establish a history of metastatic cascades. In the absence of a complete phylogeny of the subclones within the primary tumor, a scenario of parallel metastatic events from the primary tumor is an equally plausible interpretation. Future phylogenetic studies on the origin of metastases should obtain a complete phylogeny of subclones within the primary tumor. This complete phylogeny may be obtainable by ultra-deep sequencing and phasing of large sections or by targeted sequencing of many small, spatially heterogeneous sections, followed by phylogenetic reconstruction using well-established molecular evolutionary models. In addition to resolving the evolutionary history of metastases, a complete phylogeny of subclones within the primary tumor facilitates the identification of driver mutations by application of phylogeny based tests of natural selection. PMID- 26260529 TI - Indication, organization, practical implementation and interpretation guidelines for retrospective CGM recording: A French position statement. AB - AIM: The benefits of retrospective continuous glucose monitoring (retroCGM) recording have been widely explored in clinical studies, and many diabetes physicians routinely use this examination. However, the method of interpretation of CGM recordings has never been precisely described. METHOD: An expert French panel of physicians met for two days to discuss several aspects of retroCGM use and to produce a position statement. RESULTS: The guidelines cover the indications for retroCGM, the general organization and practical implementation of CGM recordings, a description of the different devices available and guidelines for the interpretation of retroCGM recordings. CONCLUSION: This consensus document should help clinicians in the proper use of retroCGM. PMID- 26260530 TI - Dissecting the cannabinergic control of behavior: The where matters. AB - The endocannabinoid system is the target of the main psychoactive component of the plant Cannabis sativa, the Delta(9)-tetrahydrocannabinol (THC). This system is composed by the cannabinoid receptors, the endogenous ligands, and the enzymes involved in their metabolic processes, which works both centrally and peripherally to regulate a plethora of physiological functions. This review aims at explaining how the site-specific actions of the endocannabinoid system impact on memory and feeding behavior through the cannabinoid receptors 1 (CB1 R). Centrally, CB1 R is widely distributed in many brain regions, different cell types (e.g. neuronal or glial cells) and intracellular compartments (e.g. mitochondria). Interestingly, cellular and molecular effects are differentially mediated by CB1 R according to their cell-type localization (e.g. glutamatergic or GABAergic neurons). Thus, understanding the cellular and subcellular function of CB1 R will provide new insights and aid the design of new compounds in cannabinoid-based medicine. Also watch the Video Abstract. PMID- 26260531 TI - Is transperineal prostate biopsy more accurate than transrectal biopsy in determining final Gleason score and clinical risk category? A comparative analysis. AB - OBJECTIVES: To assess the degree of upgrading and increase in clinical risk category of transperineal template biopsy (TTB) compared with transrectal ultrasonography-guided prostate biopsy (TRUSB). Upgrading of TRUSB Gleason grade and sum after radical prostatectomy (RP) is well recognised. TTB may offer a more thorough mapping of the prostate than TRUSB, as well as a more accurate assessment of the tumour. In this retrospective cohort study of prospectively collected data, we compare the initial TRUSB and TTB Gleason grade and sum with the final assessment at RP. PATIENTS AND METHODS: Following Ethics Committee approval, 431 laparoscopic and robotic RP specimens of two urologists, fellowship trained in minimally invasive RP, were examined in the private sector between April 2009 and October 2013. Final RP Gleason grade and sum were compared with the initial prostate biopsy. All pathological assessments were performed by a dedicated uropathology unit, experienced in prostate pathology. Upgrading was defined either as an increase in the primary Gleason grade, or as identification of a higher grade tertiary pattern at final RP analysis. Increase in clinical risk category was defined as an increase from low- (Gleason <=6), to either intermediate- (Gleason 7) or high-risk disease (Gleason 8-10); or as an increase from intermediate- to high-risk disease. The chi-squared test was used to compare categorical variables, while the Wilcoxon rank sum was used for continuous quantitative variables. RESULTS: The 431 RP specimens comprised 283 in which the prostate cancer was diagnosed at TRUSB and 148 diagnosed at TTB. There was no difference between TRUSB and TTB in mean prostate weight (46.4 vs 44.2 g), final RP pathological stage (pT2: 187 vs 102; pT3 97 vs 48; P = 0.65) or mean tumour volume (2.15 vs 2.14 mL). Overall, 33.22% of TRUSB and 30.41% of TTB were upgraded, which was not significantly different (P = 0.55). Similarly there was no difference in whether there was an increase to a higher Gleason sum (TRUSB 23.3% vs TTB 20.9%; P = 0.57). TTB was more reflective of the actual clinical risk category, with TRUSB more likely to show an increase in clinical risk (TRUSB 22.3% vs TTB 14.2%; P = 0.04). CONCLUSIONS: In this series, TTB more accurately predicted clinical risk category than TRUSB. TTB should be considered before active surveillance, to ensure that occult higher risk disease has not been under diagnosed. Upgrading and increase in clinical risk category was relatively common in each group highlighting the need for improved pretreatment staging accuracy. PMID- 26260532 TI - Effects of length dispersity and film fabrication on the sheet resistance of copper nanowire transparent conductors. AB - Development of thin-film transparent conductors (TC) based on percolating networks of metal nanowires has leaped forward in recent years, owing to the improvement of nanowire synthetic methods and modeling efforts by several research groups. While silver nanowires are the first commercially viable iteration of this technology, systems based on copper nanowires are not far behind. Here we present an analysis of TCs composed of copper nanowire networks on sheets of polyethylene terephthalate that have been treated with various oxide removing post treatments to improve conductivity. A pseudo-2D rod network modeling approach has been modified to include lognormal distributions in length that more closely reflect experimental data collected from the nanowire TCs. In our analysis, we find that the copper nanowire TCs are capable of achieving comparable electrical performance to silver nanowire TCs with similar dimensions. Lastly, we present a method for more accurately determining the nanowire area coverage in a TC over a large area using Rutherford Backscattering Spectrometry (RBS) to directly measure the metal content in the TCs. These developments will aid research and industry groups alike in the characterization of nanowire based TCs. PMID- 26260533 TI - Molecular screening of the LPCAT1 gene in patients with retinitis pigmentosa without defined mutations in known retinitis pigmentosa genes. AB - Retinitis pigmentosa (RP) is an inherited retinopathy, which affects the photoreceptors in the retina. Lysophosphatidylcholine acyltransferase (LPCAT) is a critical phospholipid biosynthesis enzyme, which promotes the conversion of lysophosphatidylcholine into phosphatidylcholine in the remodeling pathway of PC biosynthesis. A previous study reported a homozygous insertion in the LPCAT1 gene in mice exhibiting retinal degeneration (rd11). However, whether genetic mutations in LPCAT1 predispose individuals to RP remains to be elucidated. Therefore, the aim of the present study was to investigate whether LPCAT1 mutations exist in patients with RP. A total of 50 unrelated patients diagnosed with either a sporadic or recessive inheritance pattern of RP were recruited in the present study. All of the patients were comprehensively screened for genes associated with the predisposition of RP, and no pathogenic mutations were identified. Reverse transcription-polymerase chain reaction and Sanger sequencing were performed to investigate the coding regions and exon-intron boundaries of the LPCAT1 gene in the recruited patients. In total, three genetic variations in the coding regions, which lead to amino acid changes, were identified. Although two of these mutations were predicted to be pathogenic, co-segregation analysis in the pedigrees excluded these as disease-causing mutations. In addition, the LPCAT1 gene was screen in a panel of RP patients who exhibited no identifiable mutations in any of the known RP-associated genes. No disease-causing mutations in the LPCAT1 gene were identified, indicating that LPCAT1 either does not confer a genetic predisposition to RP, or that the incidence of mutations in LPCAT1 is particularly rare in patients with RP. PMID- 26260534 TI - Lithium-Salt-Containing High-Molecular-Weight Polystyrene-block-Polyethylene Oxide Block Copolymer Films. AB - Ionic conductivity in relation to the morphology of lithium-doped high-molecular weight polystyrene-block-polyethylene oxide (PS-b-PEO) diblock copolymer films was investigated as solid-state membranes for lithium-ion batteries. The tendency of the polyethylene (PEO) block to crystallize was highly suppressed by increasing both the salt-doping level and the temperature. The PEO crystallites completely vanished at a salt-doping ratio of Li/EO>0.08, at which the PEO segments were hindered from entering the crystalline unit of the PEO chain. A kinetically trapped lamella morphology of PS-b-PEO was observed, due to PEO crystallization. The increase in the lamella spacing with increasing salt concentration was attributed to the conformation of the PEO chain rather than the volume contribution of the salt or the previously reported increase in the effective interaction parameter. Upon loading the salt, the PEO chains changed from a compact/highly folded conformation to an amorphous/expanded-like conformation. The ionic conductivity was enhanced by amorphization of PEO and thereby the mobility of the PEO blocks increased upon increasing the salt-doping level. PMID- 26260535 TI - Prevalence and pattern of gluteus medius and minimus tendon pathology and muscle atrophy in older individuals using MRI. AB - PURPOSE: To evaluate gluteus medius and minimus tendon pathology and muscle atrophy in older individuals using MRI. METHODS: A retrospective MRI study of 185 individuals was performed. The inclusion criterion was age >=50. Exclusion criteria were hip surgery, fracture, infection, tumor, or inadequate image quality. Greater trochanteric bursitis was graded none, mild, moderate, or severe. Gluteus medius, gluteus minimus, and iliopsoas tendinopathy was graded normal, tendinosis, low-grade partial tear, high-grade partial tear, or full thickness tear. Gluteus medius, gluteus minimus, tensor fascia lata, and iliopsoas muscle atrophy was scored using a standard scale. Insertion site of tendinopathy and location of muscle atrophy were assessed. Descriptive and statistical analysis was performed. RESULTS: There was increasing greater trochanteric bursitis and gluteus medius and minimus tendinopathy and atrophy with advancing age with moderate to strong positive associations (p < 0.0001) for age and tendinopathy, age and atrophy, bursitis and tendinopathy, and tendinopathy and atrophy for the gluteus medius and minimus. There is a weak positive association (p < 0.0001) for age and tensor fascia lata atrophy, and no statistically significant association between age and tendinopathy or between age and atrophy for the iliopsoas. Fisher's exact tests were statistically significant (p < 0.0001) for insertion site of tendon pathology and location of muscle atrophy for the gluteus medius. CONCLUSIONS: Gluteus medius and minimus tendon pathology and muscle atrophy increase with advancing age with progression of tendinosis to low-grade tendon tears to high-grade tendon tears. There is an associated progression in atrophy of these muscles, which may be important in fall-related hip fractures. PMID- 26260536 TI - Rotator cuff tears noncontrast MRI compared to MR arthrography. AB - OBJECTIVES: To compare the accuracy of indirect magnetic resonance arthrography and noncontrast magnetic resonance imaging for diagnosing rotator cuff tears. MATERIALS AND METHODS: In total, 333 patients who underwent noncontrast magnetic resonance imaging or indirect magnetic resonance arthrography were included retrospectively. Two musculoskeletal radiologists evaluated the images for the presence of supraspinatus-infraspinatus and subscapularis tendon tears. The overall diagnostic performance was calculated using the arthroscopic findings as the reference standard. Statistical differences between the diagnostic performances of the two methods were analyzed. RESULTS: Ninety-six and 237 patients who underwent noncontrast magnetic resonance imaging and indirect magnetic resonance arthrography were assigned into groups A and B, respectively. Sensitivity for diagnosing articular-surface partial-thickness supraspinatus infraspinatus tendon tear was slightly higher in group B than in group A. Statistical significance was confirmed by multivariate analysis using the generalized estimating equation (p = 0.046). The specificity for diagnosing subscapularis tendon tear (85% vs. 68%, p = 0.012) and grading accuracy (57% vs. 40%, p = 0.005) was higher in group B than in group A; the differences were statistically significant for one out of two readers. Univariate analysis using the generalized estimating equation showed that the accuracy for diagnosing subscapularis tendon tear in group B was higher than in group A (p = 0.042). There were no statistically significant differences between the diagnostic performances of both methods for any other parameters. CONCLUSION: Indirect magnetic resonance arthrography may facilitate more accurate diagnosis and grading of subscapularis tendon tears compared with noncontrast magnetic resonance imaging. PMID- 26260537 TI - Assessment of total hip arthroplasty as a predisposing factor for ischiofemoral impingement. AB - OBJECTIVE: To examine the effect of total hip arthroplasty (THA) on ischiofemoral (IF) and quadratus femoris (QF) spaces with the hypothesis that THA does not affect ischiofemoral relationships. MATERIALS AND METHODS: The study was IRB approved and complied with HIPAA guidelines. We identified consecutive MR examinations (pelvis and/or hip) obtained at our institution in adults (>=18 years old) screened for THA-related complications. Native hips from the same individuals served as controls. We collected medical record data including age, gender, surgical history, and THA designs. Two radiologists independently measured the IF-RAD and IF-MRI (IF space on radiographs and MR imaging, respectively) and QF space (on MR imaging). Groups were compared using ANCOVA controlled for gender. RESULTS: The study group comprised 250 hips (132 subjects; 162 post-THA and 88 native hips). Subjects were aged 59 +/- 10 years, with 66 males and 66 females. Comparison of IF-MRI and QF spaces between native and post THA hips showed no differences (P > 0.12) and IF-RAD was higher in post-THA subjects (P = 0.01). No differences in the IF-MRI and QF spaces were present between native hips and different THA designs (P > 0.4). IF-RAD of metal-on-metal THA was higher than that of native hips (P = 0.01) and trended higher than ceramic-on-polyethylene THA (P = 0.08), with the remaining comparisons showing no significant differences (P > 0.4). CONCLUSIONS: Radiographic- and MRI-based measures in patients with standard THA do not show narrowing of IF and QF spaces. PMID- 26260538 TI - Effects of omega-3 PUFA on the vitamin E and glutathione antioxidant defense system in individuals at ultra-high risk of psychosis. AB - BACKGROUND: Oxidative stress and impaired antioxidant defenses are reported in schizophrenia and are associated with disturbed neurodevelopment, brain structural alterations, glutamatergic imbalance, increased negative symptoms, and cognitive impairment. There is evidence that oxidative stress predates the onset of acute psychotic illness. Here, we investigate the effects of omega-3 PUFA on the vitamin E and glutathione antioxidant defense system (AODS). METHOD: In 64 help-seeking UHR-individuals (13-25 years of age), vitamin E levels and glutathione were investigated before and after 12 weeks of treatment with either 1.2g/d omega-3 (PUFA-E) or saturated fatty acids (SFA-E), with each condition also containing 30.4mg/d alpha-tocopherol to ensure absorption without additional oxidative risk. RESULTS: In multivariate tests, the effects on the AODS (alpha tocopherol, total glutathione) were not significantly different (p=0.13, p=0.11, respectively) between treatment conditions. According to univariate findings, only PUFA-E caused a significant alpha-tocopherol increase, while PUFA-E and SFA E caused a significant gamma- and delta-tocopherol decrease. Total glutathione (GSHt) was decreased by PUFA-E supplementation. CONCLUSION: Effects of the PUFA-E condition on the vitamin E and glutathione AODS could be mechanisms underlying its clinical effectiveness. In terms of the vitamin E protection system, PUFA-E seems to directly support the antioxidative defense at membrane level. The effect of PUFA-E on GSHt is not yet fully understood, but could reflect antioxidative effects, resulting in decreased demand for glutathione. It is still necessary to further clarify which type of PUFA/antioxidant combination, and in which dose, is effective at each stage of psychotic illness. PMID- 26260539 TI - High-rate activated sludge system for carbon management--Evaluation of crucial process mechanisms and design parameters. AB - The high-rate activated sludge (HRAS) process is a technology suitable for the removal and redirection of organics from wastewater to energy generating processes in an efficient manner. A HRAS pilot plant was operated under controlled conditions resulting in concentrating the influent particulate, colloidal, and soluble COD to a waste solids stream with minimal energy input by maximizing sludge production, bacterial storage, and bioflocculation. The impact of important process parameters such as solids retention time (SRT), hydraulic residence time (HRT) and dissolved oxygen (DO) levels on the performance of a HRAS system was demonstrated in a pilot study. The results showed that maximum removal efficiencies of soluble COD were reached at a DO > 0.3 mg O2/L, SRT > 0.5 days and HRT > 15 min which indicates that minimizing the oxidation of the soluble COD in the high-rate activated sludge process is difficult. The study of DO, SRT and HRT exhibited high degree of impact on the colloidal and particulate COD removal. Thus, more attention should be focused on controlling the removal of these COD fractions. Colloidal COD removal plateaued at a DO > 0.7 mg O2/L, SRT > 1.5 days and HRT > 30 min, similar to particulate COD removal. Concurrent increase in extracellular polymers (EPS) production in the reactor and the association of particulate and colloidal material into sludge flocs (bioflocculation) indicated carbon capture by biomass. The SRT impacted the overall mass and energy balance of the high-rate process indicating that at low SRT conditions, lower COD mineralization or loss of COD content occurred. In addition, the lower SRT conditions resulted in higher sludge yields and higher COD content in the WAS. PMID- 26260540 TI - CO2-neutral wastewater treatment plants or robust, climate-friendly wastewater management? A systems perspective. AB - CO2-neutral wastewater treatment plants can be obtained by improving the recovery of internal wastewater energy resources (COD, nutrients, energy) and reducing energy demand as well as direct emissions of the greenhouse gases N2O and CH4. Climate-friendly wastewater management also includes the management of the heat resource, which is most efficiently recovered at the household level, and robust wastewater management must be able to cope with a possible resulting temperature decrease. At the treatment plant there is a substantial energy optimization potential, both from improving electromechanical devices and sludge treatment as well as through the implementation of more energy-efficient processes like the mainstream anammox process or nutrient recovery from urine. Whether CO2 neutrality can be achieved depends not only on the actual net electricity production, but also on the type of electricity replaced: the cleaner the marginal electricity the more difficult to compensate for the direct emissions, which can be substantial, depending on the stability of the biological processes. It is possible to combine heat recovery at the household scale and nutrient recovery from urine, which both have a large potential to improve the climate friendliness of wastewater management. PMID- 26260541 TI - Synergistic co-digestion of solid-organic-waste and municipal-sewage-sludge: 1 plus 1 equals more than 2 in terms of biogas production and solids reduction. AB - Making good use of existing water infrastructure by adding organic wastes to anaerobic digesters improves the energy balance of a wastewater treatment plant (WWTP) substantially. This paper explores co-digestion load limits targeting a good trade-off for boosting methane production, and limiting process-drawbacks on nitrogen-return loads, cake-production, solids-viscosity and polymer demand. Bio methane potential tests using whey as a model co-substrate showed diversification and intensification of the anaerobic digestion process resulting in a synergistical enhancement in sewage sludge methanization. Full-scale case-studies demonstrate organic co-substrate addition of up to 94% of the organic sludge load resulted in tripling of the biogas production. At organic co-substrate addition of up to 25% no significant increase in cake production and only a minor increase in ammonia release of ca. 20% have been observed. Similar impacts were measured at a high-solids digester pilot with up-stream thermal hydrolyses where the organic loading rate was increased by 25% using co-substrate. Dynamic simulations were used to validate the synergistic impact of co-substrate addition on sludge methanization, and an increase in hydrolysis rate from 1.5 d(-1) to 2.5 d(-1) was identified for simulating measured gas production rate. This study demonstrates co-digestion for maximizing synergy as a step towards energy efficiency and ultimately towards carbon neutrality. PMID- 26260543 TI - Transplantation: Mild hypothermia improves transplantation outcomes. PMID- 26260542 TI - Vascular complications in autosomal dominant polycystic kidney disease. AB - Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. Relentless cyst growth substantially enlarges both kidneys and culminates in renal failure. Patients with ADPKD also have vascular abnormalities; intracranial aneurysms (IAs) are found in ~10% of asymptomatic patients during screening and in up to 25% of those with a family history of IA or subarachnoid haemorrhage. As the genes responsible for ADPKD-PKD1 and PKD2 have complex integrative roles in mechanotransduction and intracellular calcium signalling, the molecular basis of IA formation might involve focal haemodynamic conditions exacerbated by hypertension and altered flow sensing. IA rupture results in substantial mortality, morbidity and poor long-term outcomes. In this Review, we focus mainly on strategies for screening, diagnosis and treatment of IAs in patients with ADPKD. Other vascular aneurysms and anomalies-including aneurysms of the aorta and coronary arteries, cervicocephalic and thoracic aortic dissections, aortic root dilatation and cerebral dolichoectasia-are less common in this population, and the available data are insufficient to recommend screening strategies. Treatment decisions should be made with expert consultation and be based on a risk-benefit analysis that takes into account aneurysm location and morphology as well as patient age and comorbidities. PMID- 26260544 TI - Clinical trial: Lack of benefit of MMF in IgAN. PMID- 26260545 TI - Evaluation of cerebral blood flow using multi-phase pseudo continuous arterial spin labeling at 3-tesla. AB - PURPOSE: Arterial spin labeling (ASL) methods have been widely used for evaluation of cerebral blood flow (CBF) by magnetic resonance imaging. However, ASL methods require setting of the post labeling delay (PLD) time for obtaining images. As the hemodynamic status cannot be estimated in each patient, the resultant quantitative values of blood flow may not be accurate. The multi-phase pseudo continuous arterial spin labeling (pCASL) method can be used to obtain images at various time-points. The purpose of this study was to create the transit-time maps for correcting the delayed blood flow and evaluate CBF using the transit-time maps obtained by the multi-phase pCASL method. MATERIALS AND METHODS: Twelve patients who underwent both 3.0-tesla magnetic resonance imaging (MRI) and single photon emission computed tomography with iodine-123-N-isopropyl p-iodoamphetamine (123I-IMP) were investigated. This study was approved by the institutional review board of our institution. MRI acquisitions included PLD time fixed (1525ms) and multi-phase pCASL sequences. The transit-time maps were calculated from multi-phase pCASL images by software. The transit-time maps were applied to PLD-fixed pCASL images pixel by pixel, for calculating the CBF value corrected for peak blood transit time. Regions of interest were drawn on the brain. IMP-CBF, ASL-CBF (default and corrected) and transit time were measured for each segment. RESULTS: Twelve patients and 264 segments were investigated. The mean IMP-CBF, ASL-CBF (default, corrected) and transit time were 28.4, 23.0, 29.6, [ml/min/100g] and 1977.5 [ms], respectively. There were no significant differences between IMP-CBF and ASL-CBF (corrected). CONCLUSION: CBF values can be corrected by using the transit-time maps obtained using the multi-phase pCASL method. PMID- 26260546 TI - The mechanisms of action of flavonoids in the brain: Direct versus indirect effects. AB - The projected increase in the incidence of dementia in the population highlights the urgent need for a more comprehensive understanding of how different aspects of lifestyle, in particular exercise and diet, may affect neural function and consequent cognitive performance throughout the life course. In this regard, flavonoids, found in a variety of fruits, vegetables and derived beverages, have been identified as a group of promising bioactive compounds capable of influencing different aspects of brain function, including cerebrovascular blood flow and synaptic plasticity, both resulting in improvements in learning and memory in mammalian species. However, the precise mechanisms by which flavonoids exert these actions are yet to be fully established, although accumulating data indicate an ability to interact with neuronal receptors and kinase signaling pathways which are key to neuronal activation and communication and synaptic strengthening. Alternatively or concurrently, there is also compelling evidence derived from human clinical studies suggesting that flavonoids can positively affect peripheral and cerebrovascular blood flow, which may be an indirect effective mechanism by which dietary flavonoids can impact on brain health and cognition. The current review examines the beneficial effects of flavonoids on both human and animal brain function and attempts to address and link direct and indirect actions of flavonoids and their derivatives within the central nervous system (CNS). PMID- 26260547 TI - Neuroinflammatory processes in cognitive disorders: Is there a role for flavonoids and n-3 polyunsaturated fatty acids in counteracting their detrimental effects? AB - Neuroinflammatory processes are known to contribute to the cascade of events culminating in the neuronal damage that underpins neurodegenerative disorders such as Parkinson's and Alzheimer's disease. With the ageing population and increased cases of neurodegenerative diseases, there is a crucial need for the development of new strategies capable to prevent, delay the onset or treat brain dysfunction and associated cognitive decline. Growing evidence sheds light on the use of dietary polyphenols and n-3 long chain polyunsaturated fatty acids to improve cognitive performance and reduce the neuroinflammatory and oxidative stress responses occurring with age and neurodegenerative pathologies. This review will summarise the most recent information related to the impact and mechanisms underlying the neuroinflammatory processes in neurodegenerative disorders. We will also detail the current evidence indicating that flavonoids and n-3 polyunsaturated fatty acids are strong candidates in preventing neuroinflammation and modulating age-related memory decline, and we will describe the potential mechanisms of action underlying their neuroprotective effects. As such, these dietary bioactives represent important precursor molecules in the quest to develop a new generation of drugs capable of counteracting neuroinflammation and neurodegenerative diseases. PMID- 26260548 TI - New fluorescein precursors for live bacteria detection. AB - Swiftness, reliability, and sensitivity of live bacteria detection in drinking water are key issues for human safety. The most widespread used indicator of live bacteria is a caged form of carboxyfluorescein in which 3' and 6' hydroxyl groups are masked as acetate esters (CFDA). This derivatization altogether abolishes fluorescein fluorescence and renders the molecule prone to passive diffusion through bacterial membranes. Once in the cytoplasm, acetate groups from CFDA are removed by bacterial hydrolases and fluorescence develops, rendering live but not dead cells detectable. Yet the reagent, carboxyfluorescein diacetate, still possesses a free carboxyl group whose ionization constant is such that the majority of the probe is charged at physiological pH. This unfavors probe permeation through membranes. Here, we prepare several chemical modifications of the carboxyl moiety of CFDA, in order to neutralize its charge and improve its passive diffusion through membranes. We show that the ethylamido derivative of the 5-carboxyl group from 5-carboxy-fluorescein diacetate or from Oregon green diacetate or from Oregon green diacetoxymethylester are stable molecules in biological media, penetrate into bacterial cells and are metabolized into fluorescent species. Only live bacteria are revealed since bleached samples are not labeled. Other derivatives with modification of the 5-carboxyl group with an ester group or with a thiourea-based moiety were almost inefficient probes. The most interesting probe, triembarine (5-ethylaminocarboxy-oregon green, 3',6'diacetoxymethyl ester) leads to 6-10 times more sensitive detection of bacteria as compared to CFDA. Addition of contrast agents (trypan blue or brilliant blue R) improve the signal-to-noise ratio by quenching extracellular fluorescence while bromophenol blue quenches both intracellular and extracellular fluorescence, allowing standardization of detections. PMID- 26260549 TI - Aspirin resistance and its importance. PMID- 26260550 TI - Evaluating resistance to acetyl salicylic acid using platelet function test in patients with ischemic stroke at Cipto Mangunkusumo Hospital. AB - AIM: to identify the prevalence of laboratoric ASA resistance using platelet function tests in patients with ischemic stroke at Cipto Mangunkusumo Hospital and its associated factors. METHODS: this study was a cross-sectional study involving 50 patients with ischemic stroke who only received ASA treatment. Evaluation of resistance to ASA was performed using Verifynow(r) platelet function test. ASA resistance was defined as ASA reaction unit (ARU) 550. RESULTS: there were 7 patients with ASA resistance. The mean age of subjects in ASA resistance group was 51.3+/-9.2 years; while in ASA responsive group was 57.8+/-9.7 years. In ASA resistance group, there were 85.7% male patients, 57.1% active smoker and 100% subjects with hypertension. CONCLUSION: the prevalence of laboratoric ASA resistance in patients with ischemic stroke evaluated using platelet function test at Cipto Mangunkusumo Hospital is 14%. The prevalence is more likely to occur in male patients who were active smoker, at younger age and with comorbidity of hypertension. PMID- 26260552 TI - Safety and efficacy in early insulin initiation as comprehensive therapy for patients with type 2 diabetes in primary health care centers. AB - AIM: to analyze the safety and efficacy of early insulin initiation therapy for patients with type 2 diabetes mellitus (T2DM) in primary health care provided by general practitioners (GPs) in Surabaya, East Java, Indonesia. METHODS: pre-post study of ninety nine diabetic patients without previous insulin treatment with HbA1c levels >8% were involved in this study. The study was conducted in 10 primary health care centers in Surabaya between October 2011 to June 2012. Each patient received insulin therapy for 12 weeks. Laboratory examination was performed for each patient including fasting plasma glucose (FPG), 2 hours post prandial plasma glucose (2hPPG) and HbA1c examination before and after the study. Self monitoring blood glucose (SMBG) examination was conducted in order to adjust the insulin dose and prevent the incidence of hypoglycemia. Data was statistically analyzed using paired-T test. RESULTS: FPG level was decreased from baseline data (209 mg/dL) to 152.07 mg/dL at the end of the study (56.93 mg/dl; p=0.0001). The average of 2hPPG level was also decreased from 313.00 mg/dl to 220.72 mg/dL ( 92.28 mg/dL; p=0.0001). HbA1c was reduced from 11.60% at baseline to 8.95% at the end of study ( 2.65%; p=0.0001). Hypoglycemia was found in 6 patients (6.06%) in this study, but all events were mild and did not need to be admitted to hospital. CONCLUSION: the safety of insulin therapy iniatiation might be provided by GPs at primary health centers with significant efficacy and minimal side effects. PMID- 26260551 TI - Indonesian prostate cancer risk calculator (IPCRC): an application for predicting prostate cancer risk (a multicenter study). AB - AIM: to develop a prediction risk model of prostate cancer based on Indonesia population. METHODS: we included all benign prostate hyperthrophy (BPH) and PCa patients who had prostate biopsy and prostatectomy between January 2009 and December 2013 from 5 urology centers in Indonesia. The relationship between the possibility of PCa with the following variables including: age; PSA level, prostate volume (by transabdominal ultrasound or transrectal ultrasound) and digital rectal examination (DRE) finding. We calculated a predictive scoring equation to predict the possibility of PCa using chi-square analysis, Kolmogorov Smirnov test, multiple logistic regression and ROC curve. Then, we designed an application for predicting prostate cancer risk called Indonesian Prostate Cancer Risk Calculator (IPCRC). RESULTS: there were 784 PCa and 1173 BPH patients were used for developing the risk calculator in our study. The mean ages, PSA and prostate volume are 66.9+/-8.1 years old; 72.4+/-248.9 ng/ml and 49.6+/-28.2 ml, respectively. Abnormal DRE was found in 637 PCa and 56 BPH. We included age, PSA level, abnormal DRE finding (all showed significant p<0.05 in univariate model). Additionally, although not significant, we included prostate volume (p=0.157) due to its clinical importance. The corrected ROC analysis showed AUC 0.935, sensitivity of 90.1% and specificity 80% in predicting the prostate cancer in our population. CONCLUSION: we have developed the Indonesian Prostate Cancer Risk Calculator which includes age, PSA, DRE, and prostate volume as its variables. Future prospective study to validate the risk calculator is needed. PMID- 26260553 TI - REM desensitization as a new therapeutic method for post-traumatic stress disorder: a randomized controlled trial. AB - AIM: to evaluate potential efficacy of a new therapeutic approach in posttraumatic stress disorder in comparison with eye movement desensitization and reprocessing (EMDR), a standard treatment approach and controls. METHODS: the study was designed using a randomized controlled trial methodology. Participants were recruited from military servicemen aged between 25 to 50 years who were admitting hospitals of Bushehr, Iran, with the final diagnosis of PTSD. Finally 33 male patients were devided into three subgroups: G1: EMDR; G2: REM Desensitization; and group 3: controls who received no therapy. Mississippi Scale for Posttraumatic Stress Disorder, Pittsburgh Sleep Quality Index (PSQI) and a 37 item death anxiety questionnaire were used for measures. RESULTS: multiple comparisons showed that intrusive thoughts were significantly more likely to improve with REM Desensitization versus EMDR (P=0.03), while depression was more responsive to EMDR (p=0.03). Among the Pittsburgh scale for the quality of sleep items, sleep quality (p=0.02), sleep duration (p=0.001), and total sleep quality score (p=0.002) were significantly more likely to improve in the REM Desensitization group. Change in the absolute death anxiety scores was not different between subgroups excepting EMDR versus control group (p=0.05). CONCLUSION: REM, desensitization, the new therapeutic approach to PTSD is a highly effective strategy, even more than EMDR, the standard treatment, in most of the evaluated subjects, with special emphasis on sleep symptoms, and also in the management of intrusive thoughts. Depression is the only factor in which, REM Desensitization was significantly less likely to represent a superior therapeutic effect than EMDR. PMID- 26260554 TI - Serum TNF-a, IL-8, VEGF levels in Helicobacter pylori infection and their association with degree of gastritis. AB - AIM: to investigate the serum levels of TNF-a, IL-8, VEGF in Helicobacter pylori infection, and their association with the degrees of gastritis histopathology. METHODS: a cross-sectional study was done on 80 consecutive gastritis patients admitted to endoscopy units at Adam Malik General Hospital and Permata Bunda Hospital, Medan, Indonesia from July-December 2014. The Rapid Urease test was used for the diagnosis of H. pylori infection. The severity of chronic inflammation, neutrophil infiltration, atrophy, and intestinal metaplasia were assessed. Serum samples were obtained to determine circulating TNF-a, IL-8, and VEGF. Univariate and bivariate analysis (chi square, fisher's exact, and mann whitney test) were done using SPSS version-22. RESULTS: there were 41.25% of 80 patients infected with Helicobacter pylori. Serum TNF-a and VEGF levels in the infected group were significantly higher compared to H. pylori negative, but there were no significant differences between serum levels of IL-8 in H. pylori positive and negative. There were significant associations between serum level of TNF-a and IL-8 with degree of chronic inflammation, and also between serum level of IL-8 and degree of neutrophil infiltration. There were significant associations between serum level of VEGF and degree of atrophy, and also between serum level of VEGF and degree of intestinal metaplasia. CONCLUSION: High levels of TNF-a were associated with severe degree of chronic inflammation, high levels of IL-8 associated with severe degree of chronic inflammation and neutrophil infiltration, and high levels of VEGF associated with severe degree of premalignant gastric lesion. PMID- 26260555 TI - Model and effectiveness of endurance exercise to increase physical fitness in intellectual disability subjects with obesity: a randomized controlled trial. AB - AIM: to design a model and assess the effectiveness of endurance exercise to increase physical fitness in intelectual disability (ID) patients with obesity. METHODS: a randomized-controlled clinical trial was performed in ID patients with obesity aged 10-30 years old from all Special School in DKI Jakarta, which were randomly allocated into 3 groups and then given 3 different type of exercises: lower extremity muscles endurance exercise for 20 RM followed by cardiorespiratory endurance exercise for 24-25 minutes (type I), lower extremity muscles endurance exercises for 10 RM followed by cardiorespiratory endurance exercises for 26-27 minutes (type II), and threw a tennis ball with 10 m distance for 10 minutes as control (type III). These program was performed 3 times a week for 4 months. Assesment of the exercise effectiveness was done by measuring maximum load that can be lifted and six-minutes walking test on rectangular track which was converted with the VO2 max prediction formula. Analysis was perfomed with Kruskal Wallis test. RESULTS: two hundred and twelve (212) subjects were included in the study, randomly allocated into three types (I, II, and III) of exercises groups. The type II of endurance exercise model was proved to be more effective in increasing lower extremity muscles endurance level compared to type I and III for ID patients with obesity (p<0.05). Meanwhile, type I of endurance exercise model was proved to be more effective in increasing cardiorespiratory endurance level compared to type II and III for ID patients with obesity (p<0.05). CONCLUSION: lower extremity muscles endurance exercise followed by a cardiorespiratory endurance exercise can be used to increase physical fitness in ID patients with obesity. PMID- 26260556 TI - Underutilization of anticoagulant for venous thromboembolism prophylaxis in three hospitals in Jakarta. AB - AIM: to assess the current use of anticoagulants and implementation of International Guidelines in venous thromboembolism (VTE) prophylaxis in hospitalized patients with acute medical illnesses in Jakarta, Indonesia. METHODS: a multicenter, prospective, disease registry, recruiting patients diagnosed as acutely ill medical diseases and other medical conditions at risk of VTE, with in-hospital immobilization for at least 3 days. RESULTS: of 401 patients, 46.9% received anticoagulants which included unfractionated heparin (64.4%), fondaparinux (11.7%), enoxaparin (9.6%), warfarin (3.7%), and combination of anticoagulants (10.6%). VTE prophylaxis using physical and mechanical method was used in 81.3% of patients, either as a single modality or in combination with anticoagulants. During hospitalization, VTE were found in 3.2% patients; 10 patients (2.5%) had lower limb events and 3 patients (0.75%) had a suspected pulmonary embolism. The main reference international guidelines used were AHA/ASA 2007 (47.4%), followed by ACCP 2008 (21.7%). CONCLUSION: the study showed underutilization of prophylaxis anticoagulants in which mechanical thromboprophylaxis either alone or combination with anticoagulants was the most commonly used. Unfractionated heparin was the preferable choice. The most commonly used guideline was AHA/ASA 2007. VTE thromboprophylaxis in medically ill patients needs to be encouraged. PMID- 26260557 TI - A patient with plaque type morphea mimicking systemic lupus erythematosus. AB - Morphea is an uncommon connective tissue disease with the most prominent feature being thickening or fibrosis of the dermal without internal organ involvement. It is also known as a part of localized scleroderma. Based on clinical presentation and depth of tissue involvement, morphea is classified into several forms, and about two thirds of adults with morphea have plaque type. Overproduction of collagen production by fibroblast is the cause of abnormality in morphea, and the hyperactivity mechanism of fibroblast is still unknown, although there are several mechanisms already proposed. Plaque type morphea is actually a benign and self limited. Plaque type morphea that mimicking systemic lupus erythematosus in clinical appearance, such as alopecia and oral mucosal ulcers, is uncommon. A case of plaque type morphea mimicking systemic lupus erythematosus in a 20 year old woman was discussed. The patient was treated with local and systemic immunosuppressant and antioxydant. The patient's condition is improved without any significant side effects. PMID- 26260558 TI - Malignant pleural effusion in acute myeloid leukemia with hepatitis B virus infection. AB - Pleural effusions can be the first presentation of a hematologic malignancy. The most common disorders with pleural effusion are Hodgkin and non-Hodgkin lymphoma with a frequency of 20 to 30%, especially if mediastinal involvement. Acute and chronic leukemia are rarely accompanied by pleural involvement. We describe a 46 year-old female with history of progressive dyspnoea. Physical examination was revealed massive left pleural effusion. Complete blood count revealed anemia, trombositopenia and normal leucocyte count. Viral serology test shown positive of HBsAg and total antiHBc. Chest X-ray revealed left pleural effusion. Pleural fluid cytology was myeloblast consistent with acute myeloid leukemia (AML). Bone marrow aspiration smear, bone marrow biopsy smear, and flow cytometry analysis were consistent with acute myeloid leukemia without maturation (AML M0-FAB classification). PMID- 26260559 TI - Colistin: an antibiotic and its role in multiresistant Gram-negative infections. AB - Increasing number of infection cases caused by multiresistant Gram-negative bacteria or multidrug resistant organism (MDRO) has become a major problem worldwide since there have been a lot of resistance to many classes of antibiotics. Mutant isolates such as fluoroquinolone-resistant and -lactamase resistant bacteria have been commonly found, particularly in intensive care unit (ICU). During the last two decades, there has been no study of developing antibiotics in search of discovering new type of antibiotics; meanwhile, the resistance of Gram-negative bacteria or MDRO to antibiotics is increasing. Colistin or polymyxin E is an old antibiotic, which has been used since 1959 for treating infection caused by Gram-negative MDRO. It was revealed that colistin has side effects of nephrotoxicity and neurotoxicity; therefore, the use of this antibiotic was stopped and it was replaced by other antibiotics which were effective and were considered safer at that time. There is an increasing number of infections with multi-resistant Gram-negative (MDRO) against the available antibiotics and the availability of alternative antibiotics has not been satisfying; therefore, microbiologists are searching back to the old option, which has been proven to be effective against multi-resistant Gram-negative bacteria, the old antibiotic that has been long forgotten, i.e. colistin, as an alternative treatment against Gram-negative MDRO. It is expected that colistin may have essential and reliable role as future antibiotics for treatment of multi resistant Gram-negative infections and as an alternative of antibiotics that have been available so far. PMID- 26260560 TI - The role of per oral cholangiopancreatoscopy (POCPS) in complicated pancreaticobiliary disease. AB - A fifty-five year old female patient presented with jaundice, subfebrile fever and dark yellow urine since one month before admission. She lost weight 10 kilograms during one month. One day before admission to Ciptomangunkusumo General Hospital, she complained of worsened abdominal pain at right upper quadrant urging her to come to the emergency room. An abdominal examination revealed Murphy sign, mild hepatomegaly and deeply icteric sclera. Serum bilirubin was 21.8 mg/dl, alkaline phosphatase and gamma-glutamyltransferase levels were significantly elevated (1090 IU/L and 560 IU/L consecutively) while the transaminases were moderately high (ALT 80 U/L). The C-reactive protein was 555 mg/L. An abdominal ultrasound examination revealed dilatation of right and left intrahepatic bile duct and presence of common hepatic duct stone. Subsequent magnetic resonance imaging/magnetic cholangiopancreatography (MRI/MRCP) revealed intrahepatic bile duct dilatation, multiple CBD stone and benign stricture at common hepatic duct causing right and left intrahepatic bile duct obstruction.We assessed the patient as acute cholangitis and obstructive jaundice suspected to be caused by biliary duct stone then we performed endoscopic retrograde cholangiopancreatography (ERCP), we revealing stenosis at distal CBD, multiple CBD stone, giant stone in CHD and dilatation of bilateral IHBD. We performed CBD stone extraction then inserted biliary stent for drainage. Then we planned to do second ERCP with SpyGlassTM for giant stone extraction. After the first ERCP, the clinical condition of the patient improved and the bilirubin decreased to 10 mg/dL. In the next two weeks we performed a second ERCP to extract the giant stone with SpyGlass TM. However, after we inserted SpyGlassTM into the biliary duct, what we found were not as we expected before. We revealed that there was a mass in biliary duct and there was no CBD stone. We did the biopsy and inserted a new plastic stent (after removed the older one) to the common biliary duct. Surprisingly, the result of histopathology also supports our findings, which was the adenocarcinoma at common bile duct. PMID- 26260561 TI - Tranexamic acid in the management of upper gastrointestinal bleeding: an evidence based case report. AB - AIM: to review the effectiveness of tranexamic acid therapy which has been proposed to reduce bleeding and in turn lower mortality rate. METHODS: following literature searching based on our clinical question on Cochrane Library, PubMed, Clinical Key, EBSCO, Science Direct and Proquest, one systematic review that includes seven randomized controlled trials is obtained. The article meets validity and relevance criteria. RESULTS: the systematic review found that there is no any clear evidence between intervention and control groups in term of mortality. CONCLUSION: the use of tranexamic acid to reduce mortality in patients with upper gastrointestinal bleeding is not recommended. PMID- 26260562 TI - Controversy: hirudotherapy (leech therapy) as an alternative treatment for osteoarthritis. AB - Osteoarthritis (OA) is the most common degenerative joint disease found in the elderly. Drug options that are recommended by the American Academy of Orthopaedic Surgeon (AAOS) are acetaminophen, NSAIDs, tramadol, capscaicin and intraarticular corticosteroids. However, there is concern for the possible side effects resulting from long term use of those medications. Researchers are searching for a safer treatment modality for OA. Leech therapy (hirudotheraphy) is one of the therapies under investigation, given its purported analgesic and antiinflammatory properties. PMID- 26260563 TI - Productive and reproductive performances of dairy cattle herds in Treviso province, Italy (2009-2012): an assessment of the potential impact of Schmallenberg virus epidemic. AB - BACKGROUND: Schmallenberg virus (SBV) has spread across Europe since mid-2011, causing unspecific and transitory symptoms in ruminants and congenital malformations in their offspring. Evidence for the impact of SBV on cattle (re)productive performance is limited. Using a comprehensive data set from a SBV affected province in North-East Italy, this study aimed at assessing the potential impact of SBV emergence on 11 productive and reproductive performance indicators of dairy cattle herds, accounting for weather conditions and other herd-level factors that could also influence these indicators. RESULTS: A total of 127 farms with an average of 71 cows per farm (range 29-496) were monitored monthly from January 2009 to June 2012. Mixed-effects linear models for longitudinal data were used to assess the average variation in herds' performance indicators over semesters (Jan-Jun 2009, Jul-Dec 2009, Jan-Jun 2010, Jul-Dec 2010, Jan-Jun 2011, Jul-Dec 2011, Jan-Jun 2012) and trimesters therein. Taking the second semester of 2011 as reference, significant decreases in the average lactation length (-6 days, on average) and calving-to-conception interval (-4 days, on average) were observed relative to the same semesters of the years 2010 and 2009, respectively. Similarly, during the last trimester of 2011, which is most likely to cover the SBV infection period in the study area, there was an average decrease of -4 days (lactation length) and -7 days (calving-to-conception interval) compared to the same trimesters of the years 2010 and 2009, respectively. However, the observed decreases actually represent a positive outcome that is not as such imputable to SBV emergence, but rather reflects other beneficial changes in farm management. None of the other indicators showed significant variations, confirming the relatively mild expression of SBV infection in cattle. CONCLUSIONS: Although the emergence of SBV might have significantly affected the (re)productive performance of some individual farms, we concluded that overall at the province level there were no significant variations attributable to SBV, at least not in a way that would lead to negative effects on farm profitability. PMID- 26260564 TI - Catatonia in inpatients with psychiatric disorders: A comparison of schizophrenia and mood disorders. AB - This study aimed to evaluate the symptom threshold for making the diagnosis of catatonia. Further the objectives were to (1) to study the factor solution of Bush Francis Catatonia Rating Scale (BFCRS); (2) To compare the prevalence and symptom profile of catatonia in patients with psychotic and mood disorders among patients admitted to the psychiatry inpatient of a general hospital psychiatric unit. 201 patients were screened for presence of catatonia by using BFCRS. By using cluster analysis, discriminant analysis, ROC curve, sensitivity and specificity analysis, data suggested that a threshold of 3 symptoms was able to correctly categorize 89.4% of patients with catatonia and 100% of patients without catatonia. Prevalence of catatonia was 9.45%. There was no difference in the prevalence rate and symptom profile of catatonia between those with schizophrenia and mood disorders (i.e., unipolar depression and bipolar affective disorder). Factor analysis of the data yielded 2 factor solutions, i.e., retarded and excited catatonia. To conclude this study suggests that presence of 3 symptoms for making the diagnosis of catatonia can correctly distinguish patients with and without catatonia. This is compatible with the recommendations of DSM-5. Prevalence of catatonia is almost equal in patients with schizophrenia and mood disorders. PMID- 26260565 TI - The relationship between chronotype and mood fluctuation in the general population. AB - There is a lack of evidence for the relationship between chronotype and subthreshold mood fluctuation. The present study aims to investigate the relationship between chronotypes and mood fluctuation in the general population. Participants (n=302) who have had no experience of major mood episodes were included. The Korean version of the Composite Scale of Morningness (CSM) was used to classify participants according to three chronotypes. Mood fluctuation was measured using the Mood Disorder Questionnaire (MDQ) and the Bipolar Spectrum Diagnostic Scale (BSDS). Mean scores achieved by the three chronotype groups on the MDQ and the BSDS were compared. There were no significant differences in the frequency of positive responses on the MDQ for the three chronotype groups. However, there was a significant group difference in total BSDS scores. The eveningness group had significantly higher BSDS-D scores than did either the morningness or the intermediate group have. In addition, the eveningness group had significantly higher BSDS-M scores than the morningness group. After adjusting for age by the analysis of covariance (ANCOVA), there were still significant group differences in total BSDS scores. The present results suggest that eveningness may be more related to mood fluctuation than morningness. The eveningness may be an important factor related to soft bipolarity or mood fluctuation. PMID- 26260566 TI - The outcomes of psychiatric inpatients by proportion of experienced psychiatrists and nurse staffing in hospital: New findings on improving the quality of mental health care in South Korea. AB - Readmission rates for mental health care are higher in South Korea than other Organization for Economic Development (OECD) countries. Therefore, it is worthwhile to continue investigating how to reduce readmissions. Taking a novel approach, we determined the relationship between psychiatrist experience and mental health care readmission rates. We used National Health Insurance claim data (N=21,315) from 81 hospitals to analyze readmissions within 30 days of discharge for "mood disorders" or "schizophrenia, schizotypal and delusional disorders" during 2010-2013. In this study, multilevel models that included both patient and hospital-level variables were analyzed to examine associations with readmission. Readmissions within 30 days of discharge accounted for 1079 (5.1%) claims. Multilevel analysis demonstrated that the proportion of experienced psychiatrists at a hospital was inversely associated with risk of readmission (OR: 0.79, 95% CI: 0.74-0.84 per 10% increase in experienced psychiatrists). Readmission rates for psychiatric disorders within 30 days of discharge were lower in hospitals with a higher number of nurses (OR: 0.95, 95% CI: 0.94-0.96 per 10 nurses). In conclusion, health policymakers and hospital managers should make an effort to reduce readmissions for psychiatric disorders and other diseases by considering the role that physician experience plays and nurse staffing. PMID- 26260567 TI - Suicidality in clozapine-treated patients with schizophrenia: role of obsessive compulsive symptoms. AB - Patients with schizophrenia have an increased lifetime risk of comorbid obsessive compulsive symptoms. Up to 30% of these patients experience such symptoms and 12% may be diagnosed with obsessive-compulsive disorder. The presence of these symptoms in schizophrenia seems to be associated with poor outcomes including a greater suicidal risk. A subgroup of patients develops this symptomatology after the initiation with Second Generation Antipsychotics (SGA). Also, there is evidence of a causal relationship for this association, particularly for clozapine. The primary aim of this study was to investigate the association of this comorbidity with suicidality in a population of clozapine-medicated schizophrenic and schizoaffective patients (N=65). The prevalence of obsessive compulsive symptoms in our sample was 29.2% (N=19) and the prevalence of obsessive-compulsive disorder was 13.8% (N=9). Significant positive correlations between suicidality and total Y-BOCS score and between Y- BOCS score and depressive symptoms were found. Further analysis indicated that a Y-BOCS score greater or equal than 8 was an independent predictor of suicide attempt during clozapine treatment. Routine screening for this adverse event should be warranted for this population. PMID- 26260568 TI - Erythrocyte fatty acid profiles and plasma homocysteine, folate and vitamin B6 and B12 in recurrent depression: Implications for co-morbidity with cardiovascular disease. AB - Oxidative stress induced interactions between fatty acid (FA) and one-carbon metabolism may be involved in co-occurrence of major depressive disorder (MDD) and cardiovascular disease (CVD), which have been scarcely studied together. In 137 recurrent MDD-patients vs. 73 age- and sex-matched healthy controls, we simultaneously measured key components of one-carbon metabolism in plasma (homocysteine, folate, vitamins B6 and B12), and of FA-metabolism in red blood cell membranes [main polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) and structural FA indices (chain length, unsaturation, peroxidation)]. Results show significant positive associations of folate with EPA, DHA, and the peroxidation index, which were similar in patients and controls. After correction for confounders, these associations were lost except for EPA. Associations between B-vitamins and FA parameters were non-significant, but also similar in patients and controls. Homocysteine and DHA were significantly less negatively associated in patients than in controls. In conclusion, these data indicate similarities but also differences in associations between parameters of one-carbon and FA-metabolism in recurrent MDD patients vs. controls, which may reflect differences in handling of oxidative stress. Further research should test the consequences of these differences, particularly the premature development of CVD in MDD. PMID- 26260569 TI - The roles of social stress and decision-making in non-suicidal self-injury. AB - Research suggests that individuals with a history of non-suicidal self-injury (NSSI) do not have difficulty generating alternatives to social problems but choose more negative solutions, suggesting a deficit in decision-making. However, studies report no significant differences in risky decision-making on a performance-based task among individuals with and without NSSI histories. A limitation of these studies is that decision-making was only assessed at baseline. As individuals with a history of NSSI typically self-injure when experiencing negative emotions, decision-making ability may become impaired specifically in the presence of these emotions. The aim of the current study was to investigate decision-making ability among individuals with and without NSSI histories both at baseline and following a distressing social exclusion task. We compared individuals with (n=48) and without (n=72) NSSI histories on the Iowa Gambling Task, a behavioral measure of risky decision-making, before and after exclusion or inclusion on the Cyberball task. Results indicated no significant group differences in performance regardless of condition. When participants were grouped by racial/ethnic minority status, results indicated that non-Hispanic White individuals with a history of NSSI exhibited deterioration in risky decision-making ability following social exclusion. Potential explanations for these findings and clinical implications are discussed. PMID- 26260570 TI - Bright versus dim ambient light affects subjective well-being but not serotonin related biological factors. AB - Light falling on the retina is converted into an electrical signal which stimulates serotonin synthesis. Previous studies described an increase of plasma and CNS serotonin levels after bright light exposure. Ghrelin and leptin are peptide hormones which are involved in the regulation of hunger/satiety and are related to serotonin. Neopterin and kynurenine are immunological markers which are also linked to serotonin biosynthesis. In this study, 29 healthy male volunteers were exposed to bright (5000lx) and dim (50lx) light conditions for 120min in a cross-over manner. Subjective well-being and hunger as well as various serotonin associated plasma factors were assessed before and after light exposure. Subjective well-being showed a small increase under bright light and a small decrease under dim light, resulting in a significant interaction between light condition and time. Ghrelin concentrations increased significantly under both light conditions, but there was no interaction between light and time. Correspondingly, leptin decreased significantly under both light conditions. Hunger increased significantly with no light-time interaction. We also found a significant decrease of neopterin, tryptophan and tyrosine levels, but no interaction between light and time. In conclusion, ambient light was affecting subjective well-being rather than serotonin associated biological factors. PMID- 26260571 TI - The influence of self-relevant materials on working memory in dysphoric undergraduates. AB - Difficulties in updating working memory (WM) may underlie problems with regulating emotions that contribute to depression. To examine the ability of updating affective materials in WM, 33 dysphoric and 34 non-dysphoric participants were asked to evaluate the self-descriptiveness of emotional adjectives and provide answers to self-relevant questions. Within 3-7 days, they completed a two-back task with a series of self-irrelevant or self-relevant emotional words (they had generated previously) and four conditions (match-set, break-set, perseveration-set, and no-set). After the WM task, an unexpected recall task was administered; controls recalled more positive self-relevant words and intrusions while dysphoric participants recalled more negative self-relevant words and intrusions. In break-set trials of the two-back task, dysphoric individuals showed slower response to self-relevant words regardless of valence. In the match-set and perseveration-set trials, dysphoric participants showed delayed response to self-related negative words. Moreover, longer reaction times for self-relevant negative words were correlated with higher rumination and worse depression. The results suggest that dysphoric undergraduates are interfered more by and have a better memory of self-relevant negative stimuli in WM, which is closely correlated with rumination. This study is among the first to confirm the potential mechanism that could underwrite the involvement of self-schema in effectively regulating negative affect. PMID- 26260572 TI - The Canadian Assessment of Physical Literacy: methods for children in grades 4 to 6 (8 to 12 years). AB - BACKGROUND: Physical literacy is described as the motivation, confidence, physical competence, knowledge and understanding to value and engage in a physically active lifestyle. As such, it is expected that those who have greater physical literacy would be more likely to obtain the health benefits offered by habitual physical activity. A theoretical model and assessment battery, the Canadian Assessment of Physical Literacy (CAPL), for the assessment of childhood physical literacy had been proposed in theory but validity data were lacking. The purpose of this study was to explore validity evidence for the CAPL among children in grades 4 to 6. METHODS: CAPL validity was evaluated through three analyses that utilized cross-sectional data obtained through local schools in Eastern Ontario, Canada. A confirmatory factor analysis compared the data to the theoretical model. Patterns of association between self-reported age and gender and the CAPL total and domain scores were examined using regression models. Teacher ratings of participants' knowledge, attitude and physical activity competence were compared to assessment results. RESULTS: The CAPL was completed by 963 children (55 % female) in grades 4, 5 and 6. Children were 8 to 12 years of age (mean 10.1 years), with 85 % of children approached agreeing to participate. A confirmatory factor analysis using data from 489 children with complete raw scores supported a model with four domains: engagement in physical activity (active and sedentary), physical competence (fitness and motor skill), motivation and confidence, and knowledge and understanding. Raw domain scores followed expected patterns for age and gender, providing evidence for their validity. Interpretive categories, developed from age and gender adjusted normative data, were not associated with age indicating that the CAPL is suitable for use across this age range. Children's gender was associated with the physical competence, motivation and engagement in physical activity domain scores, indicating that further research is required regarding the gender adjustment of the raw CAPL scores. CAPL domain and total scores were statistically significantly associated with teacher ratings of the child's motivation, attitudes, fitness, skill and overall physical activity. CONCLUSIONS: CAPL offers a comprehensive assessment of engagement in physical activity, physical competence, motivation and confidence, and knowledge and understanding as components of childhood (grades 4 to 6, 8 to 12 years) physical literacy. Monitoring of these measures enhances our understanding of children's physical literacy, and assists with the identification of areas where additional supports are required. PMID- 26260573 TI - Near Infrared Spectroscopy Detection and Quantification of Herbal Medicines Adulterated with Sibutramine. AB - There is an increasing demand for herbal medicines in weight loss treatment. Some synthetic chemicals, such as sibutramine (SB), have been detected as adulterants in herbal formulations. In this study, two strategies using near infrared (NIR) spectroscopy have been developed to evaluate potential adulteration of herbal medicines with SB: a qualitative screening approach and a quantitative methodology based on multivariate calibration. Samples were composed by products commercialized as herbal medicines, as well as by laboratory adulterated samples. Spectra were obtained in the range of 14,000-4000 per cm. Using PLS-DA, a correct classification of 100% was achieved for the external validation set. In the quantitative approach, the root mean squares error of prediction (RMSEP), for both PLS and MLR models, was 0.2% w/w. The results prove the potential of NIR spectroscopy and multivariate calibration in quantifying sibutramine in adulterated herbal medicines samples. PMID- 26260574 TI - Supply of benzathine penicillin G: the 20-year experience in Australia. PMID- 26260575 TI - The social context of wild leafy vegetables uses in Shiri, Daghestan. AB - BACKGROUND: Shiri is a small mountainous village in the Republic of Daghestan, in the North Caucasus. Daghestan is Russia's southernmost and most ethnically and linguistically diverse republic, a considerable part of which belongs to the Caucasus Biodiversity Hotspot. Various species of wild leafy vegetables are collected in Shiri and there are still many social and cultural practices connected with plant collection in the village. Yet due to migration processes, local knowledge about wild greens and their uses is being slowly forgotten or not passed on. The Shiri language is highly endangered and so are the local plant terminologies and classifications. The unstable political situation hinders local and international research, therefore we find it highly important to explore both what wild leafy vegetables are collected in this mountainous part of Daghestan and how the relation between plants and people is shaped in this linguistically and culturally diverse context. We answer the following questions: what wild leafy vegetables are collected in Shiri? Why are they important to the local people? What is the social aspect of wild leafy vegetable uses? METHODS: The methods applied were as follows: forest walks and semi-structured interviews with adult inhabitants of Shiri village, participant and non-participant observation. During the walks herbarium specimens were collected, and visual recording of plant collecting process was conducted. This article is based on fieldwork done in Shiri, Daghestan, between 2012 and 2014, over the course of 3 field trips that took place in 3 seasons. RESULTS: We collected and identified twenty-two local (24 botanical) species of wild leafy vegetables. Fourteen local species were used as snacks, eight for cooked dishes and three of them were also dried in order to be transported to kin living in the lowlands. It is significant that 70 % of taxa collected in Shiri are used as snacks. While snacks were collected by both sexes, greens for cooking and drying were part of the women's knowledge. The analysis of people-plant relations showed that care practices constitute an important part of these relations. Through the giving of wild greens, Shiri people express care for co-villagers and migrants and show their respect for elders. In the narratives about wild greens, their nutritional and taste value as well as perceived exceptionality were emphasized. CONCLUSIONS: 1) Wild leafy vegetables are a significant element of everyday social life in Shiri in regard to mutual care, respect for elders and local identity. 2) Gender has a greater influence on practical skills than on declarative plant knowledge. 3) Names of plants are publicly discussed with elders and are not always fixed. 4) The moral value ascribed to giving in the local culture is expressed through wild leafy vegetables. 5) Care expressed through sending wild leafy vegetables helps to sustain social ties between migrants and Shiri inhabitants. 6) Identity, health and naturalness discourses are adding value to the local knowledge about wild leafy vegetables. PMID- 26260576 TI - Thermoresponsive Random Poly(ether urethanes) with Tailorable LCSTs for Anticancer Drug Delivery. AB - A new class of thermoresponsive random polyurethanes is successfully synthesized and characterized. Poly(ethylene glycol) diol (Mn = 1500 Da) and 2,2 dimethylolpropionic acid are reacted with isophorone diisocyanate in the presence of methane sulfonic acid catalyst. It is found that these polyurethanes are thermoresponsive in aqueous media and manifest a lower critical solution temperature (LCST) that can be easily tuned from 30 degrees C to 70 degrees C by increasing the poly(ethylene glycol) content. Their sharp LCST transitions make these random polyurethanes ideal candidates for stimuli-responsive drug delivery applications. To that end, the ability of these systems to efficiently sequester doxorubicin (up to 36 wt%) by means of a sonication/dialysis method is successfully demonstrated. Additionally, it is also demonstrated that accelerated doxorubicin release kinetics from the nanoparticles can be attained above the LCST. PMID- 26260577 TI - The microstructure of coaching practice: behaviours and activities of an elite rugby union head coach during preparation and competition. AB - The activities and behaviours of a female head coach of a national rugby union team were recorded in both training and competition, across a whole rugby season, using the newly developed Rugby Coach Activities and Behaviours Instrument (RCABI). The instrument incorporates 24 categories of behaviour, embedded within three forms of activity (training form (TF), playing form (PF) and competitive match) and seven sub-activity types. In contrast to traditional drill-based coaching, 58.5% of the training time was found to have been spent in PF activities. Moreover, the proportion of PF activities increased to a peak average of 83.8% in proximity to the team's annual international championship. Uniquely, one of the coach's most prolific behaviours was conferring with associates (23.3%), highlighting the importance of interactions with assistant coaches, medical staff and others in shaping the coaching process. Additionally, the frequencies of key behaviours such as questioning and praise were found to vary between the different activity forms and types, raising questions about previous conceptions of effective coaching practice. The findings are discussed in the light of the Game Sense philosophy and the role of the head coach. PMID- 26260578 TI - A label-free electrochemical affisensor for cancer marker detection: The case of HER2. AB - In this paper, we report the development of a sensitive label-free impedimetric biosensor based on the use of affibody as bioreceptor and gold nanostructured screen-printed graphite as a sensor platform for the detection of human epidermal growth factor receptor 2 (HER2). The affisensor is realized by immobilizing a terminal cysteine-modified affibody on gold nanoparticles. The sensor was characterized by electrochemical techniques and scanning electron microscopy (SEM). Furthermore, surface plasmon resonance (SPR) technology was also applied to explore the potential of affibodies as small-molecule discriminating tools. Using optimized experimental conditions, a single-use affisensor showed a good analytical performance for HER2 detection from 0 to 40 MUg/L. The estimated limit of detection was 6.0 MUg/L. Finally, the realized affisensor was applied to human serum samples. PMID- 26260579 TI - Bioelectrical impedance vector analysis in critically ill patients: a prospective, clinician-blinded investigation. AB - INTRODUCTION: Assessment of fluid status in critically ill patients is challenging. We aimed to assess the feasibility and validity of bioelectrical impedance vector analysis (BIVA) as a measure of hydration in critically ill patients. METHODS: We performed twice-daily BIVA measurements and fluid balance calculations and recorded physiological variables in mechanically ventilated patients within 24 h of intensive care unit (ICU) admission for up to 5 days. Treating clinicians were blinded to BIVA results. RESULTS: We performed 344 BIVA measurements in 61 patients. According to BIVA, 14 patients (23%) were dehydrated, 22 (36%) were normally hydrated and 25 (41%) were overhydrated upon ICU admission. Patients with normal BIVA hydration were less sick, had fewer comorbidities and had less deranged physiology than patients found to be dehydrated or overhydrated with BIVA. Cumulative fluid balance increased in patients found to be dehydrated with BIVA by a mean of 3.4+/-2.2 L, whereas in patients found to be overhydrated with BIVA, it decreased by a mean of 4.5+/-6.9 L. In patients found to be normally hydrated with BIVA, fluid balance remained unchanged. BIVA-defined hydration increased with 1 L (median change 1.5%, P =0.09) or 2 L (median change 0.7%, P =0.09) of calculated fluid gains. BIVA defined hydration decreased (median change -0.8%, P =0.02) with a negative cumulative fluid balance of >2 L. BIVA-defined hydration between first and last measurement correlated with the corresponding change in fluid balance (rho =0.25, P =0.05). CONCLUSIONS: BIVA is feasible in critically ill patients. Its validity is supported by the observed characteristics of patients with different degrees of BIVA hydration upon admission and by different fluid management of such patients by blinded clinicians. The sensitivity of repeated BIVA hydration measurements to detect fluid accumulation or fluid balance changes <2 L was low, however. These contradictory findings provide the rational basis for studies of BIVA-assisted fluid management in ICU patients. PMID- 26260581 TI - Defining the Path Between Social and Economic Factors, Clinical and Lifestyle Determinants, and Cardiovascular Disease. AB - BACKGROUND: Low socioeconomic status is associated with poorer cardiovascular health. OBJECTIVES: The aim of the present work was to evaluate how social and economic factors influence modifiable cardiovascular disease risk factors and thus, acute coronary syndrome or ischemic stroke presence. METHODS: One thousand participants were enrolled; 250 consecutive patients with a first acute coronary syndrome (83% were male, 60 +/- 12 years old) and 250 control subjects, as well as 250 consecutive patients with a first ischemic stroke (56% were male, 77 +/- 9 years old) and 250 control subjects. The control subjects were population-based and age-sex matched with the patients. Detailed information regarding their medical records, lifestyle characteristics, education level, financial status satisfaction, and type of occupation were recorded. RESULTS: After controlling for potential confounding factors, significant inverse associations were observed regarding financial status satisfaction and sedentary/mental type occupation with acute coronary syndrome or stroke presence, but not with the educational level. Nevertheless, further evaluation using path analysis, revealed quite different results, indicating that the education level influenced the type of occupation and financial satisfaction, hence affecting indirectly the likelihood of developing a cardiovascular disease event. CONCLUSIONS: Social and economic parameters interact with modifiable cardiovascular disease risk factors through multiple pathways. PMID- 26260580 TI - Adverse childhood experiences and health-related quality of life in adulthood: revelations from a community needs assessment. AB - BACKGROUND: Adverse childhood experiences (ACE) have been previously linked to quality of life, health conditions, and life expectancy in adulthood. Less is known about the potential mechanisms which mediate these associations. This study examined how ACE influences adult health-related quality of life (HRQoL) in a low income community in Florida. METHODS: A community-based participatory needs assessment was conducted from November 2013 to March 2014 with 201 residents of Tampa, Florida, USA. HRQoL was measured by an excessive number of unhealthy days experienced during the previous 30-day window. Mediation analyses for dichotomous outcomes were conducted with logistic regression. Bootstrapped confidence intervals were generated for both total and specific indirect effects. RESULTS: Most participants reported 'good to excellent health' (76%) and about a fourth reported 'fair to poor health' (24%). The mean of total unhealthy days was 9 days per month (SD +/- 10.5). Controlling for demographic and neighborhood covariates, excessive unhealthy days was associated with ACE (AOR = 1.23; 95% CI: 1.06, 1.43), perceived stress (AOR = 1.07; 95% CI: 1.03, 1.10), and sleep disturbance (AOR = 8.86; 3.61, 21.77). Mediated effects were significant for stress (beta = 0.08) and sleep disturbances (beta = 0.11) as they related to the relationship between ACE and excessive unhealthy days. CONCLUSION: ACE is linked to adult HRQoL. Stress and sleep disturbances may represent later consequences of childhood adversity that modulate adult quality of life. PMID- 26260582 TI - Synergistic induction of apoptosis by a polo-like kinase 1 inhibitor and microtubule-interfering drugs in Ewing sarcoma cells. AB - Since polo-like kinase 1 (PLK1) is highly expressed in Ewing sarcoma (ES), we evaluated the therapeutic potential of the PLK1 inhibitor BI 6727. Here, we identify a synergistic induction of apoptosis by BI 6727 and several microtubule interfering drugs in ES cells, including vincristine (VCR), vinblastine (VBL), vinorelbine (VNR) and eribulin. Synergistic drug interaction is confirmed by calculation of combination index (CI). Also, BI 6727 and VCR act in concert to reduce long-term clonogenic survival. Mechanistically, BI 6727/VCR co-treatment cooperates to trigger mitotic arrest, phosphorylation of BCL-2 and BCL-XL and downregulation of MCL-1. This inactivation of anti-apoptotic BCL-2 family proteins in turn promotes activation of BAX and BAK, activation of caspase-9 and 3 and caspase-dependent apoptosis. Overexpression of BCL-2 or simultaneous knockdown of BAX and BAK significantly rescue BI 6727/VCR-induced apoptosis, indicating that engagement of the mitochondrial pathway is critical for BI 6727/VCR-mediated apoptosis. The clinical relevance of PLK1 inhibitor-based combination therapies is underscored by the fact that BI 6727 is currently evaluated in phase I clinical trials in childhood cancer. In conclusion, PLK1 inhibitors such as BI 6727 may provide a new strategy to chemosensitize ES. PMID- 26260583 TI - S1 nerve is the most efficient nerve rootlet innervating the anal canal and rectum in rats. AB - Autonomic and somatic components participate in the defecation process in mammals, combining signals from the brainstem and forebrain. The innervation pattern involved in micturition in rats has been well studied, while defecation has been less studied. The aim of the present study was to identify the most important sensory and motor nerves of the anal canal and rectum involved in defecation. The amplitudes of evoked potential of the anal canal and rectum were higher when L6 and S1 ventral rootlets were stimulated, compared with the other segments (ANOVA and Tukey's post hoc test, all P < 0.05). The S1 segment was more strongly cholera toxin subunit B conjugated to horseradish peroxidase (CB-HRP) positive compared with the other segments (ANOVA and Tukey's post hoc test, P < 0.05). Ventral spinal rootlets of L6 and S1 mainly contributed to the pressure change in the anal canal and rectum when the ventral spinal rootlets from L5 to S3 were stimulated electrically. In conclusion, many afferent and efferent nerves innervate the anal canal and rectum and are involved in defecation, but the S1 nerve rootlet could be the most efficient one. These results could provide a basis for defecation reconstruction, especially for patients with spinal cord injuries. PMID- 26260585 TI - Differential attentional responding in caesarean versus vaginally delivered infants. AB - Little is known about the role that the birth experience plays in brain and cognitive development. Recent research has suggested that birth experience influences the development of the somatosensory cortex, an area involved in spatial attention to sensory information. In this study, we explored whether differences in spatial attention would occur in infants who had different birth experiences, as occurs for caesarean versus vaginal delivery. Three-month-old infants performed either a spatial cueing task or a visual expectation task. We showed that caesarean-delivered infants' stimulus-driven, reflexive attention was slowed relative to vaginally delivered infants', whereas their cognitively driven, voluntary attention was unaffected. Thus, types of birth experience influence at least one form of infants' attention, and possibly any cognitive process that relies on spatial attention. This study also suggests that birth experience influences the initial state of brain functioning and, consequently, should be considered in our understanding of brain development. PMID- 26260584 TI - PLAG1 and NCAPG-LCORL in livestock. AB - A recent progress on stature genetics has revealed simple genetic architecture in livestock animals in contrast to that in humans. PLAG1 and/or NCAPG-LCORL, both of which are known as a locus for adult human height, have been detected for association with body weight/height in cattle and horses, and for selective sweep in dogs and pigs. The findings indicate a significant impact of these loci on mammalian growth or body size and usefulness of the natural variants for selective breeding. However, association with an unfavorable trait, such as late puberty or risk for a neuropathic disease, was also reported for the respective loci, indicating an importance to discriminate between causality and association. Here I review the recent findings on quantitative trait loci (QTL) for stature in livestock animals, mainly focusing on the PLAG1 and NCAPG-LCORL loci. I also describe our recent efforts to identify the causative variation for the third major locus for carcass weight in Japanese Black cattle. PMID- 26260586 TI - Pelvic Inflammatory Disease in Virgin Women With Tubo-ovarian Abscess: A Single Center Experience and Literature Review. AB - STUDY OBJECTIVE: To evaluate the incidence of pelvic inflammatory disease (PID) in virgin women and investigate the clinical characteristics of the patients. DESIGN: Retrospective chart review and literature review. SETTING: Tertiary academic center. PARTICIPANTS: Virgin women who were confirmed to have PID via surgery from 2002 to 2014. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The evaluation of medicosurgical history, clinical progress, surgical record, and pathologic reports. RESULTS: Of 122 patients diagnosed with PID via surgery, 5 women were virgins (4.1%). The median age was 21 years (range, 14-24 years), and all patients presented with abdominal pain. The median diameter of the pelvic abscess pocket on preoperative imaging was 4.5 cm (range, 2.6-15 cm). Only 1 case was preoperatively diagnosed as a tubo-ovarian abscess; the others were expected to be benign ovarian tumors, such as endometrioma and dermoid cysts. No possible source of infection was identified for any patient, except 1 who had a history of an appendectomy because of a ruptured appendix. The results of the histopathological analysis of the excisional biopsy performed during surgery in 4 cases were consistent with acute suppurative inflammation. After postoperative antibiotic use, the conditions of all patients stabilized, and they were discharged from the hospital on median postoperative day 9. CONCLUSION: PID in virgin women is rare, but it should be considered in all women with abdominal pain, regardless of sexual history. PMID- 26260588 TI - Job strain and coping among ageing baby boomers. AB - BACKGROUND: Research indicates that the so-called baby boomer generation (the population born after World War II) exhibits worrying health trends. Taking age cohort effects into account, it is still unclear how the mechanisms concerning stress and health function and how the distribution of stressors, stress mediators and stress effects on health differ between generations. OBJECTIVES: The article approaches stress from a generational perspective asking: which are the stressors the baby boomer generation is facing? Under which conditions and with which resources is exposure to stressors harmful to health? Is there an accumulation of stress in later working life? MATERIAL AND METHODS: In the course of the project "Wellbeing", a quantitative online survey was carried out in selected commercial enterprises and public institutions in four project partner countries. The results for Austrian participants are presented in this article. RESULTS: Employees of the baby boomer generation are exposed to both time-related and social stressors at the workplace and a high percentage of respondents expressed symptoms of physical and psychological stress. Stress mediators, such as agency-based coping strategies and social resources at the workplace could buffer these stressors; however, stressors and stress mediators are significantly correlated creating a "triple whammy" effect (i.e. exposure to stressors, lack of social resources and restricted coping), which particularly affects older male baby boomers. CONCLUSION: Social support buffers the negative effects of a limited health and lower education for female baby boomers, which supports the buffering hypothesis of social convoy theory, whereas male baby boomers lack the resources to effectively cope with work stress. PMID- 26260589 TI - [Burdens and coping strategies of informal caregivers. The perspective of informal caregivers]. AB - BACKGROUND AND AIM: Taking care of a person at the end of life at home is difficult and challenging. In a qualitative study, the burdens experienced by informal caregivers as well as their coping strategies to face these burdens were investigated. MATERIAL AND METHODS: Narrative interviews with 25 informal caregivers were conducted. Interviews were transcribed verbatim and analyzed using a constant comparative approach. RESULTS: Informal caregivers feel tired and overburdened, alone and abandoned, experience grief and fear, feel helpless and experience a feeling of having lost control over their own life. To cope with these stressful emotions, they actively seek help and support, inform themselves and acquire skills and competencies, talk to others, allow themselves time off and emphasize the positive and meaningful aspects of caring for someone at home. CONCLUSION: The burdens experienced by informal caregivers are highly subjective and depend on the coping strategies and the available resources. A main resource is the help and support provided by the informal social network. PMID- 26260590 TI - Purification of Stabilized GPCRs for Structural and Biophysical Analyses. AB - G protein-coupled receptors (GPCRs) are of particular importance for drug discovery, being the targets of many existing drugs, and being linked to many diseases where new therapies are required. However, as integral membrane proteins, they are generally unstable when removed from their membrane environment, precluding them from the wide range of structural and biophysical techniques which can be applied to soluble proteins such as kinases. Through the use of protein engineering methods, mutations can be identified which both increase the thermostability of GPCRs when purified in detergent, as well as biasing the receptor toward a specific physiologically relevant conformational state. The resultant stabilized receptor (known as a StaR) can be purified in multiple-milligram quantities, whilst retaining correct folding, thus enabling the generation of reagents suitable for a broad range of structural and biophysical studies. Example protocols for the purification of StaR proteins for analysis, ligand screening with the thiol-specific fluorochrome N-[4-(7 diethylamino-4-methyl-3-coumarinyl)phenyl]maleimide (CPM), surface plasmon resonance (SPR), and crystallization for structural studies are presented. PMID- 26260587 TI - IL10-driven STAT3 signalling in senescent macrophages promotes pathological eye angiogenesis. AB - Macrophage dysfunction plays a pivotal role during neovascular proliferation in diseases of ageing including cancers, atherosclerosis and blinding eye disease. In the eye, choroidal neovascularization (CNV) causes blindness in patients with age-related macular degeneration (AMD). Here we report that increased IL10, not IL4 or IL13, in senescent eyes activates STAT3 signalling that induces the alternative activation of macrophages and vascular proliferation. Targeted inhibition of both IL10 receptor-mediated signalling and STAT3 activation in macrophages reverses the ageing phenotype. In addition, adoptive transfer of STAT3-deficient macrophages into eyes of old mice significantly reduces the amount of CNV. Systemic and CD163(+) eye macrophages obtained from AMD patients also demonstrate STAT3 activation. Our studies demonstrate that impaired SOCS3 feedback leads to permissive IL10/STAT3 signalling that promotes alternative macrophage activation and pathological neovascularization. These findings have significant implications for our understanding of the pathobiology of age associated diseases and may guide targeted immunotherapy. PMID- 26260591 TI - Purification and Crystallization of a Thermostabilized Agonist-Bound Conformation of the Human Adenosine A(2A) Receptor. AB - Crystallization of G protein-coupled receptors (GPCRs) is successful due to the development of generic protein engineering strategies, which has resulted in the structure determination of more than 25 GPCRs, including representatives from class A, B, C, and F. Most of the X-ray structures available correspond to an inactive conformation of the receptor bound to an antagonist. Only a few high resolution structures of agonist-bound conformations of GPCRs have been determined over the last 6 years. Here, we describe the purification and crystallization protocols of a thermostabilized agonist-bound conformation of the human adenosine A2A receptor. PMID- 26260592 TI - 2D Projection Analysis of GPCR Complexes by Negative Stain Electron Microscopy. AB - While electron cryo-microscopy (cryo-EM) of biological specimens is the preferred single particle EM method for structure determination, its application is very challenging for the typically small (<150 kDa) complexes between GPCRs and their partner proteins. Negative stain EM, whereby the biological samples are embedded in a thin layer of heavy metal solution, is a well-established alternative technique that provides the enhanced contrast needed to visualize small macromolecular complexes. This methodology can offer a simple and powerful tool for the rapid evaluation of sample characteristics, such as homogeneity or oligomeric state. When coupled to single particle classification and averaging, negative stain EM can provide valuable information on the overall architecture and dynamics of protein complexes. Here we provide a concise protocol for negative stain imaging and two-dimensional (2D) projection analysis of GPCR complexes, including notes for the intricacies of the application in these biological systems. PMID- 26260593 TI - Nuts and Bolts of CF3 and CH 3 NMR Toward the Understanding of Conformational Exchange of GPCRs. AB - With the advent of efficient protein expression and functional purification protocols, it is now possible to reconstitute many G protein-coupled receptors (GPCRs) in detergent micelles at concentrations of 25 MUM or more. Such concentrations are sufficient for studies of conformational states and dynamics relating to function and the mechanism of activation of GPCRs, using solution state NMR. In particular, methyl spectroscopy, in the form of one-dimensional (19)F NMR or two-dimensional ((1)H,(13)C) NMR, provides high fidelity spectra which reveal detailed features associated with conformational states and their lifetimes, as a function of ligand. While X-ray crystallography provides exquisitely detailed structures of lowest energy states associated with ligands, G proteins, and other proteins, NMR is able to validate such states, while providing insight into higher energy states that form part of the conformational landscape and are involved in activation. Through relaxation experiments spanning microseconds to seconds, lifetimes of these functional states can often be measured. By determining the effect of ligands on both equilibrium populations and rates of interconversion between states, it becomes possible to understand activation in terms of an ensemble description and in turn relate the ensemble to pharmaceutical phenomena. PMID- 26260594 TI - Single-Molecule Fluorescence Microscopy for the Analysis of Fast Receptor Dynamics. AB - Assessing the dynamics of individual membrane proteins in living cells is a powerful approach to investigate their assembly, mobility, and function. Here, we describe how to image single G protein-coupled receptors (GPCRs), both in the active and inactive state. This is achieved by combining labeling of GPCRs with bright organic fluorophores and fluorescent imaging by total internal reflection fluorescence microscopy. Using this method, individual tracks of single molecules can be analyzed in parallel with high spatial precision and with frame rates up to 50/s. PMID- 26260595 TI - Quantitative Multi-color Detection Strategies for Bioorthogonally Labeled GPCRs. AB - We describe multiple bioorthogonal approaches to label G protein-coupled receptors (GPCRs) heterologously expressed in mammalian cells. The use of genetically encoded unnatural amino acids as bioorthogonal tags results in receptors that are expressed at lower levels than even their low abundance wild type counterparts. Therefore, reproducible and sensitive quantification of the labeled GPCRs is extremely important and conventional methods are simply not sufficiently accurate and precise. Silver stains lack reproducibility, spectroscopic methods using fluorescent ligands are limited to quantifying only functional receptor molecules, and immunoassays using epitope tags derived from rhodopsin are particularly variable for low-abundance GPCRs. To avoid these shortcomings, we employ near infrared (NIR) imaging-based methods that enable simultaneous multi-color detection of two different antigens, thus facilitating the ratiometric analysis of bioorthogonally modified GPCRs. We anticipate that these multi-color detection strategies will provide new tools for quantitatively assessing stoichiometrically labeled GPCRs for studies of signalosomes and for structure-function relationships at a single molecule level. PMID- 26260596 TI - Approaches to Characterize and Quantify Oligomerization of GPCRs. AB - Fluorescence resonance energy transfer (FRET) is an approach widely used to detect protein-protein interactions in live cells. This approach is based on the sensitization of an "acceptor" molecule by the energy transfer from a "donor" when there is an overlap between the emission spectrum of the "donor" and the excitation spectrum of the "acceptor" and close proximity between the two fluorophore species (in the region of 8 nm). Various methods exist to quantify FRET signals: here, we describe the application of homogeneous time-resolved FRET (htrFRET) combined with Tag-liteTM technology and its application to determine not only protein-protein interactions but also the capability of GPCR mutant variants to form homomers compared to the wild type GPCR within the plasma membrane of transfected cells. PMID- 26260597 TI - Monitoring G Protein Activation in Cells with BRET. AB - Live-cell assays based on fluorescence and luminescence are now indispensable tools for the study of G protein signaling. Assays based on fluorescence and bioluminescence resonance energy transfer (FRET and BRET) have been particularly valuable for monitoring changes in second messengers, protein-protein interactions, and protein conformation. Here, we describe a BRET assay that monitors the release of free Gbetagamma dimers after activation of heterotrimers containing Galpha subunits from all four G protein subfamilies. This assay provides useful kinetic and pharmacological information with reasonably high throughput using a standard laboratory equipment. PMID- 26260598 TI - Use of Fluorescence Indicators in Receptor Ligands. AB - Fluorescence techniques can provide insights into the environment of fluorescence indicators incorporated within a ligand as it is bound to its receptor. Fluorescence indicators of different sizes and chemical characteristics can provide insights into the nature of the binding environment, the surrounding structures, and even into conformational changes associated with receptor activation. Methods for determining fluorescence spectral analysis, fluorescence quenching, fluorescence anisotropy, fluorescence lifetimes, and red edge excitation shifts of the ligand probes are described. The applications of these techniques to the CCK1 receptor occupied by alexa(488)-CCK and aladan-CCK, as examples of probes developed (1) by derivatization of an existing peptide and (2) by incorporation during peptide synthesis, are utilized as examples. These methods represent powerful tools to expand our understanding of the structure and molecular basis of ligand activation of G protein-coupled receptors. PMID- 26260599 TI - Detection and Quantification of Intracellular Signaling Using FRET-Based Biosensors and High Content Imaging. AB - Forster resonance energy transfer (FRET) biosensors represent invaluable tools to detect the spatiotemporal context of second messenger production and intracellular signaling that cannot be attained using traditional methods. Here, we describe a detailed protocol for the use of high content imaging in combination with FRET biosensors to assess second messenger production and intracellular signaling in a time-effective manner. We use four different FRET biosensors to measure cAMP levels, kinase (ERK and PKC), and GTPase activity. Importantly, we provide the protocols to express and measure these sensors in a variety of model cell lines and primary dorsal root ganglia neurons. PMID- 26260600 TI - The Measurement of Receptor Signaling Bias. AB - This chapter describes a method to quantify biased signaling effects of agonists; this approach can furnish a scale for medicinal chemists to optimize biased profiles. Biased ligands have different pharmacological properties on a molecular level (stabilization of different receptor active states) and thus can have different pharmacological profiles therapeutically. The calculation of transduction ratios (DeltaDeltalog(tau/K A)) values (where tau is efficacy and K A a measure of affinity) allows the identification of agonists that demonstrate unique signaling either for different signaling pathways linked to the receptor, differences in cellular host, effects of receptor mutation, or receptor selectivity profiles. The procedure includes statistical methods to assess the significance of these effects. PMID- 26260601 TI - Approaches to Assess Functional Selectivity in GPCRs: Evaluating G Protein Signaling in an Endogenous Environment. AB - Ligand-directed signaling, biased agonism, and functional selectivity are terms that describe the propensity of a ligand to drive signaling toward one GPCR pathway over another. Most of the early examples demonstrated to date examine the divergence between GPCR signaling to G protein coupling and betaarrestin2 recruitment. As biased agonists begin to become available based on cell-based screening criteria, a need arises to determine if G protein signaling biases will be maintained in the endogenous setting, wherein receptors are functioning to control relevant biological responses. This report presents our method and offers tips for evaluating G protein signaling in endogenous tissues. Predominately, brain tissues are discussed here; optimization points that can be applied to any tissues are highlighted. PMID- 26260602 TI - Bioluminescence Resonance Energy Transfer Approaches to Discover Bias in GPCR Signaling. AB - Bioluminescence resonance energy transfer (BRET) is a well-established technique for investigating G protein-coupled receptor (GPCR) pharmacology. BRET enables the monitoring of molecular proximity through the use of heterologously expressed proteins of interest and/or fluorophore-labeled ligands. Fusion to a donor luciferase enzyme or an acceptor fluorophore and subsequent detection of resonance energy transfer indicate the close proximity of the molecules of interest. As BRET is readily applied to the study of numerous GPCR signaling and regulatory paths, it is an ideal technique for investigating the pharmacology of biased ligands and receptors. PMID- 26260603 TI - Virus-Mediated Expression of DREADDs for In Vivo Metabolic Studies. AB - During the past few years, CNO-sensitive designer G protein-coupled receptors (GPCRs) known as DREADDs (designer receptors exclusively activated by designer drugs) have emerged as powerful new tools for the study of GPCR physiology. In this chapter, we present protocols employing adeno-associated viruses (AAVs) to express a Gq-coupled DREADD (Dq) in two metabolically important cell types, AgRP neurons of the hypothalamus and hepatocytes of the liver. We also provide examples dealing with the metabolic analysis of the Dq mutant mice after administration of CNO in vivo. The approaches described in this chapter can be applied to other members of the DREADD family and, of course, different cell types. It is likely that the use of DREADD technology will identify physiologically important signaling pathways that can be targeted for therapeutic purposes. PMID- 26260604 TI - High-Throughput Screening for Allosteric Modulators of GPCRs. AB - The continued evolution of our understanding of G protein-coupled receptor (GPCR) signaling has revealed new opportunities for drug discovery. Specifically, biased agonism at GPCRs and allosteric modulation of GPCRs both represent emerging areas of GPCR biology that hold promise for the development of novel GPCR-targeted therapeutics that may provide greater therapeutic efficacy and/or improved side effect profiles. To obtain initial chemical leads, high-throughput screening (HTS) of a large compound library for the desired activity is often deployed during the early stages of a discovery program. The identification of allosteric modulators, in particular, poses significant challenges for HTS. We describe several HTS protocols designed for the identification of GPCR ligands, with a particular focus on the identification of allosteric modulators. PMID- 26260605 TI - Radioligand Binding Assay for an Exon 11-Associated Mu Opioid Receptor Target. AB - Receptor binding provides a valuable approach for characterization of drugs and their receptors. There are three major families of opioid receptors: mu, delta, and kappa. Highly selective radioligands are available for all three classes of traditional receptors. Of the three, the mu receptor undergoes extensive alternative splicing, generating a number of traditional mu receptor subtypes as well as a nontraditional, truncated set of variants associated with exon 11. These exon 11-associated truncated variants are not readily labeled with current radioligands. Here we describe the synthesis of a radioiodinated ligand suitable for carrying out binding studies for this target. PMID- 26260606 TI - Docking and Virtual Screening Strategies for GPCR Drug Discovery. AB - Progress in structure determination of G protein-coupled receptors (GPCRs) has made it possible to apply structure-based drug design (SBDD) methods to this pharmaceutically important target class. The quality of GPCR structures available for SBDD projects fall on a spectrum ranging from high resolution crystal structures (<2 A), where all water molecules in the binding pocket are resolved, to lower resolution (>3 A) where some protein residues are not resolved, and finally to homology models that are built using distantly related templates. Each GPCR project involves a distinct set of opportunities and challenges, and requires different approaches to model the interaction between the receptor and the ligands. In this review we will discuss docking and virtual screening to GPCRs, and highlight several refinement and post-processing steps that can be used to improve the accuracy of these calculations. Several examples are discussed that illustrate specific steps that can be taken to improve upon the docking and virtual screening accuracy. While GPCRs are a unique target class, many of the methods and strategies outlined in this review are general and therefore applicable to other protein families. PMID- 26260607 TI - The Dynamic Process of Drug-GPCR Binding at Either Orthosteric or Allosteric Sites Evaluated by Metadynamics. AB - Major advances in G Protein-Coupled Receptor (GPCR) structural biology over the past few years have yielded a significant number of high-resolution crystal structures for several different receptor subtypes. This dramatic increase in GPCR structural information has underscored the use of automated docking algorithms for the discovery of novel ligands that can eventually be developed into improved therapeutics. However, these algorithms are often unable to discriminate between different, yet energetically similar, poses because of their relatively simple scoring functions. Here, we describe a metadynamics-based approach to study the dynamic process of ligand binding to/unbinding from GPCRs with a higher level of accuracy and yet satisfying efficiency. PMID- 26260608 TI - Experiment-Guided Molecular Modeling of Protein-Protein Complexes Involving GPCRs. AB - Experimental structure determination for G protein-coupled receptors (GPCRs) and especially their complexes with protein and peptide ligands is at its infancy. In the absence of complex structures, molecular modeling and docking play a large role not only by providing a proper 3D context for interpretation of biochemical and biophysical data, but also by prospectively guiding experiments. Experimentally confirmed restraints may help improve the accuracy and information content of the computational models. Here we present a hybrid molecular modeling protocol that integrates heterogeneous experimental data with force field-based calculations in the stochastic global optimization of the conformations and relative orientations of binding partners. Some experimental data, such as pharmacophore-like chemical fields or disulfide-trapping restraints, can be seamlessly incorporated in the protocol, while other types of data are more useful at the stage of solution filtering. The protocol was successfully applied to modeling and design of a stable construct that resulted in crystallization of the first complex between a chemokine and its receptor. Examples from this work are used to illustrate the steps of the protocol. The utility of different types of experimental data for modeling and docking is discussed and caveats associated with data misinterpretation are highlighted. PMID- 26260609 TI - Interaction Fingerprints and Their Applications to Identify Hot Spots. AB - Binding recognition is in the core of how nature controls processes in living cells, how enzyme-substrate binding leads to catalysis and how drugs modulate enzymes and receptors to convey a desirable physiological response. Thus, understanding binding recognition in a systematic manner is paramount, not only to understand biological processes but also to be able to design and discover new bioactive compounds. One such way to analyze binding interactions is through the development of binding interaction fingerprints. Here, we present the methodology to develop interaction fingerprints with three different software platforms along with two representative examples. PMID- 26260610 TI - The Ideal Anticoagulation Strategy in ST-Elevation Myocardial Infarction. AB - Heparin has been the principal anticoagulant in the management of ST-elevation myocardial infarction (STEMI) but has several limitations. Although glycoprotein IIb/IIIa inhibitors have been major adjuncts in previous years, in the era of novel P2Y12 receptor inhibitors they may have a greater role in bailout. Low molecular weight heparins have been extensively studied in fibrinolysis trials but data in primary percutaneous coronary intervention (PCI) are scarce. The direct thrombin inhibitor bivalirudin overcomes several shortcomings of heparins and has demonstrated a significant reduction in bleeding outcomes and net adverse cardiac events at the cost of increased acute stent thrombosis. This review discusses the pharmacology and clinical trial evidence for different anticoagulant treatment options in STEMI with a proposed selection strategy in contemporary primary PCI. PMID- 26260611 TI - Rate control versus rhythm control in atrial fibrillation: lessons learned from clinical trials of atrial fibrillation. AB - Ample evidence supports the statement that in patients with atrial fibrillation in whom treatment is warranted, either rhythm control or rate control are acceptable primary therapeutic options. If a rhythm control strategy is chosen, it is important to consider that recurrence of atrial fibrillation is not treatment failure per se. Occasional recurrence, with cardioversion if necessary, may be quite acceptable. The latter will depend on the frequency, duration and symptoms associated with recurrence, and may require a change in the rhythm control therapy, e.g., change the antiarrhythmic drug, or initiate or redo atrial fibrillation ablation. And a rhythm control strategy should include careful attention to and treatment of comorbidities (hypertension, heart failure, diabetes, etc.). If a rate control strategy is chosen, treatment with a beta blocker or nondihydropyridine calcium channel blocker is almost always required to achieve adequate rate control. Digoxin is often useful to obtain satisfactory rate control in combination with a beta blocker or nondihydropyridine calcium channel blocker. Digoxin may be useful as primary therapy in the presence of hypotension or heart failure. Satisfactory ventricular rate control is usually a resting rate less than 110 beats per minute, although resting rates below 90 beats per minute are probably wiser. Finally, when pursuing a rhythm control strategy, because recurrence of atrial fibrillation is common, rate control therapy should be a part of the treatment regimen. PMID- 26260612 TI - Platelet Reactivity: Is There a Role to Switch? AB - Antiplatelet agents are essential to prevent thrombotic events in patients with coronary artery disease, especially in those with acute coronary syndrome or undergoing percutaneous coronary intervention (PCI). However, the benefits of antiplatelet therapy always come at a price of increased risk for bleeding, and the clinical values of antiplatelet strategies depend on this characteristic benefit/risk ratio. Platelet function testing aiming at determining an individual's response to the administered agent was hoped to help balance bleeding and thrombosis in order to maximize benefit/risk ratio. However, randomized trials failed to demonstrate an improved clinical outcome of a platelet function-based treatment selection and consequently platelet function testing has not become a routine part of the management of antiplatelet therapies. This review aims to discuss results and shortcomings of available trials and registries regarding the potential role of platelet reactivity testing in guiding antiplatelet treatment selection in patients undergoing PCI. PMID- 26260613 TI - HOXD10 acts as a tumor-suppressive factor via inhibition of the RHOC/AKT/MAPK pathway in human cholangiocellular carcinoma. AB - HOXD10, a key regulator of cell-differentiated phenotype maintainence, has been demonstrated to be involved in the tumorigenesis of many human malignacies. However, the status of HOXD10 expression and its biological function in cholangiocellular carcinoma (CCC) remain to be clarified. In the present study, we investigated the clinical significance and biological functions of HOXD10 in CCC and found that the expression of HOXD10 and its downstream effector RHOC was significantly different in well-differentiated CCC tissues compared with poorly differentiated lesions. We also observed a significant correlation between low HOXD10 and high RHOC expression levels and worse prognosis. The stable overexpression of HOXD10 by lentivirus vector significantly inhibited cell invasion partly by downregulating the expression of MMP2 and MMP9, and significantly increased early apoptosis in CCC cell lines and induced G1 phase cell cycle arrest, contributing to the inhibition of cell proliferation in vitro. Additionally, we demonstrated that the inactivation of the RHOC/AKT/MAPK pathway was involved in the tumor-suppressive functions of HOXD10 in CCC. These results suggested that HOXD10 may be a putative suppressor gene and can act as a prognostic marker and potentially a novel therapeutic target for CCC. PMID- 26260614 TI - Integrated miRNA-mRNA analysis in the habenula nuclei of mice intravenously self administering nicotine. AB - A considerable amount of evidence suggests that microRNAs (miRNAs) play crucial roles in the neuroadaptation of drug addiction. Habenula (Hb), one of the critical brain regions involved in reward and addiction, can be divided into two anatomically and transcriptionally distinct regions: medial habenula (MHb) and lateral habenula (LHb) nuclei. However, very few studies have compared the functional roles of these regions. Here, by using mirConnX integrator and KEGG pathway mapping, we simultaneously analysed the differential expression patterns of miRNAs and messenger RNA (mRNA) within MHb and LHb under nicotine addiction. Significantly altered miRNAs and mRNAs were found in the Hb of mice intravenously self-administering nicotine. Interestingly, some miRNAs were oppositely regulated between the MHb and the LHb, and their potential targets included various genes of cell signalling pathways related to the degeneration of fasciculus retroflexus (FR). This study provides an improved insight into the differential regulation of habenular transcripts in nicotine addiction, as well as the potential functions of miRNAs in several biological pathways involved in the nicotine addiction. PMID- 26260616 TI - Probing the importance of lipid diversity in cell membranes via molecular simulation. AB - Lipid membranes in prokaryotes and eukaryotes have a wide array of lipids that are necessary for proper membrane structure and function. In this paper, an introduction to lipid diversity in biology and a mini-review on how molecular simulations have been used to model biological membranes (primarily limited to one to three lipid types in most simulation-based models) is provided, which motivates the use of all-atom molecular dynamics (MD) simulations to study the effect of lipid diversity on properties of realistic membrane models of prokaryotes and eukaryotes. As an example, cytoplasmic membrane models of Escherichia coli were developed at different stages of the colony growth cycle (early-log, mid-log, stationary and overnight). The main difference between lipid compositions at each stage was the concentration of a cyclopropane-containing moiety on the sn-2 lipid acyl chain (cyC17:0). Triplicate MD simulations for each stage were run for 300 ns to study the influence of lipid diversity on the surface area per lipid, area compressibility modulus, deuterium order parameters, and electron density profiles. The overnight stage (also known as the death stage) had the highest average surface area per lipid, highest rigidity, and lowest bilayer thickness compare to other stages of E. coli cytoplasmic membrane. Although bilayer thickness did depend on the growth stage, the changes between these were small suggesting that the hydrophobic core of transmembrane proteins fit well with the membrane in all growth stages. Although it is still common practise in MD simulations of membrane proteins to use simple one- or two component membranes, it can be important to use diverse lipid model membranes when membrane protein structure and function are influenced by changes in lipid membrane composition. PMID- 26260615 TI - Telomerase activity promotes osteoblast differentiation by modulating IGF signaling pathway. AB - The contribution of deficient telomerase activity to age-related decline in osteoblast functions and bone formation is poorly studied. We have previously demonstrated that telomerase over-expression led to enhanced osteoblast differentiation of human bone marrow skeletal (stromal) stem cells (hMSC) in vitro and in vivo. Here, we investigated the signaling pathways underlying the regulatory functions of telomerase in osteoblastic cells. Comparative microarray analysis and Western blot analysis of telomerase-over expressing hMSC (hMSC-TERT) versus primary hMSC revealed significant up-regulation of several components of insulin-like growth factor (IGF) signaling. Specifically, a significant increase in IGF-induced AKT phosphorylation and alkaline phosphatase (ALP) activity were observed in hMSC-TERT. Enhanced ALP activity was reduced in presence of IGF1 receptor inhibitor: picropodophyllin. In addition, telomerase deficiency caused significant reduction in IGF signaling proteins in osteoblastic cells cultured from telomerase deficient mice (Terc(-/-)). The low bone mass exhibited by Terc( /-) mice was associated with significant reduction in serum levels of IGF1 and IGFBP3 as well as reduced skeletal mRNA expression of Igf1, Igf2, Igf2r, Igfbp5 and Igfbp6. IGF1-induced osteoblast differentiation was also impaired in Terc(-/ ) MSC. In conclusion, our data demonstrate that impaired IGF/AKT signaling contributes to the observed decreased bone mass and bone formation exhibited by telomerase deficient osteoblastic cells. PMID- 26260619 TI - Transdermal delivery of tadalafil using a novel formulation. AB - The aim of this work was to investigate the transdermal gel loaded with tadalafil, a practically insoluble selective phosphodiesterase-5 inhibitor (PDE5) in order to improve the solubility and bioavailability. The solubility of tadalafil in mixed solution of hydroxypropyl-beta-cyclodextrin (HPCD), polyethylene glycol (PEG) 400 and tween 80 (T2 solution) was 260.8 +/- 4.3 ug/mL and that of tadalafil in modified T2 (M-T2) solution, which tadalafil was dissolved in 20% (w/v) HPCD at first and then mixture solutions of PEG 400 and tween 80 were added, was increased to 344.9 +/- 30.6 ug/mL. Four gel formulae were prepared, subsequently in vitro and in vivo skin permeation studies were carried out. Interestingly, tadalafil gel in M-T2 and oleic acid (OA) (F3) could promote the percutaneous absorption of tadalafil by 179.4% in vitro and increase AUC by 223% in vivo compared with tadalafil gel in the absence of M-T2 and OA (F1). Also, there was a finding that tadalafil gel in M-T2 and OA did not cause dermal irritations in an experimental animal. PMID- 26260617 TI - Usefulness of a crista catheter for 3-dimensional electroanatomical mapping of complex right atrial tachyarrhythmias. AB - PURPOSE: Right atrial (RA) tachyarrhythmias are not rare in patients with congenital heart disease and a history of cardiac surgery. This study investigated the usefulness of a crista catheter for 3-dimensional electroanatomical mapping of RA tachyarrhythmias. METHODS: We consecutively included 35 patients (age, 43.2 +/- 15.6 years; 15 men) who underwent an electrophysiological study with 3-dimensional electroanatomical mapping for RA tachycardia or flutter. In 13 patients with atrial flutter, we recorded and compared the electrical sequence in the anterior and posterior portions of the RA lateral wall. We used a crista catheter as a mapping catheter for 3-dimensional mapping in 12 patients (crista group), a lasso catheter in 12 patients (lasso group), and an ablation catheter in 11 patients (ablation group). We compared the 3-dimensional mapping points, time, and speed (mapping points per minute) among the groups. RESULTS: Atrial flutter was confirmed as cavotricuspid isthmus dependent in all patients whose two atrial electrical sequences were the same direction and as atypical (including scar-related and dual-loop) in all patients whose sequences were in the opposite direction. Mapping speed in the crista group was significantly faster than in the lasso and ablation groups: median (interquartile range) 44.0 (35.5-69.4) points/min, 23.7 (17.8-29.8) points/min, and 8.2 (4.8-11.0) points/min, respectively (p = 0.001). CONCLUSIONS: A crista catheter is useful for high-density 3-dimensional electroanatomical mapping of complex RA tachyarrhythmias. Comparison of the electrical sequences in the anterior and posterior portions of the RA lateral wall is helpful for differentiating between cavotricuspid isthmus-dependent and atypical atrial flutter. PMID- 26260620 TI - Advances in nanotechnology-based carrier systems for targeted delivery of bioactive drug molecules with special emphasis on immunotherapy in drug resistant tuberculosis - a critical review. AB - From the early sixteenth and seventeenth centuries to the present day of life, tuberculosis (TB) still is a global health threat with some new emergence of resistance. This type of emergence poses a vital challenge to control TB cases across the world. Mortality and morbidity rates are high due to this new face of TB. The newer nanotechnology-based drug-delivery approaches involving micro metric and nano-metric carriers are much needed at this stage. These delivery systems would provide more advantages over conventional systems of treatment by producing enhanced therapeutic efficacy, uniform distribution of drug molecule to the target site, sustained and controlled release of drug molecules and lesser side effects. The main aim to develop these novel drug-delivery systems is to improve the patient compliance and reduce therapy time. This article reviews and elaborates the new concepts and drug-delivery approaches for the treatment of TB involving solid-lipid particulate drug-delivery systems (solid-lipid micro- and nanoparticles, nanostructured lipid carriers), vesicular drug-delivery systems (liposomes, niosomes and liposphere), emulsion-based drug-delivery systems (micro and nanoemulsion) and some other novel drug-delivery systems for the effective treatment of tuberculosis and role of immunomodulators as an adjuvant therapy for management of MDR-TB and XDR-TB. PMID- 26260621 TI - The diagnostic value of tumor markers in bronchoalveolar lavage fluid for the peripheral pulmonary carcinoma. AB - BACKGROUND: To investigate the value of Ubiquitin specific peptidase 8 (USP8), Chitinase 3-like 1 (YKL40), Heat shock protein 90a (HSP90alpha), glutathione S transferase P1 (GSTP1), carcinoembryonic antigen (CEA), neuron specific enolase (NSE) and cytokeratin fragment antiogen 21-1 (CYFRA21-1) in bronchoalveolar lavage fluid (BALF) and serum for diagnosis in patients with peripheral lung cancer. METHODS: The concentration of these markers were measured in 50 patients with peripheral lung cancer and 50 patients with benign lung diseases by using enzyme-linked immuno sorbent assay methods. RESULTS: There were significant differences between the peripheral lung cancer group and the benign lung disease group (P < 0.05) in the BALF of USP8, YKL40, HSP90alpha, CEA, NSE and CYFRA21-1. There were significant differences between the peripheral lung cancer group and the benign lung disease group (P < 0.05) in the serum of HSP90alpha and CEA. There were no differences in others. There were no correlation between the concentration of all markers and age, histological type, TNM stage (I-IV). There was a weak correlation between the primary foci diameters and the concentration of YKL40 in BALF. (Pearson's correlation: 0.203, P = 0.048) The diagnostic efficiencies of USP8, YKL40, HSP90alpha were superior to CYFRA21-1 and NSE, being lower CEA. CONCLUSION: Detection of tumor markers in BALF was superior to serum specimens. The measurement of USP8, HSP90alpha and YKL40 in BALF had more clinical value for the diagnosis of peripheral pulmonary carcinoma. PMID- 26260622 TI - Routine systemic antibiotic prophylaxis for burn injuries in developing countries: A best evidence topic (BET). AB - BACKGROUND: Burns are common in low- and middle-income countries (LMICs) and complicated by unhygienic conditions, malnutrition, use of high-risk homemade dressings and delayed presentation. Resultantly, use of routine systemic antibiotic prophylaxis (SAP) to prevent wound infection is common practice despite this intervention being abandoned in high-income countries due to increased antimicrobial resistance and non-bacterial suprainfection. METHODS: A best evidence topic (BET) was constructed using a structured protocol. The question addressed was: In LMICs, does routine use of SAP reduce burn wound infection, morbidity or mortality? RESULTS: From 704 retrieved records, 48 reports met criteria to be examined. Of those, 3 studies represented the best available evidence. Together, two randomized clinical trials (RCTs) and a retrospective cohort study reported no difference in the proportion of wound infection, any infection or length of hospital stay between SAP groups and controls. One RCT described a greater proportion of wounds infected with P. aeruginosa among SAP arms compared to controls. The studies had few participants and significant methodological weaknesses. CONCLUSION: On the basis of limited, currently available evidence, the use of SAP cannot be recommended for patients in LMICs that present soon after burn injury. PMID- 26260623 TI - Characteristics associated with alcohol consumption among emergency department patients presenting with road traffic injuries in Hyderabad, India. AB - INTRODUCTION: Each year in India, road traffic crashes lead to more than 200,000 deaths and the country has seen an unprecedented rate of roadway fatalities in recent years. At the same time, alcohol consumption per capita among Indians is rising. Despite these increasing trends of road traffic injuries (RTIs) and alcohol use, alcohol is not routinely assessed as a risk factor for RTIs. This study aims to examine the involvement of alcohol among emergency department patients presenting with RTIs in the Indian city of Hyderabad. PATIENTS AND METHODS: As part of a prospective study, data were collected from 3366 patients (88.0% male) presenting with RTIs at an emergency department in Hyderabad, India, from September 2013 to February 2014. Logistic regression models were used to assess individual-level and road traffic crash characteristics associated with suspected or reported alcohol consumption six hours prior to the RTI. RESULTS: Alcohol was suspected or reported among 17.9% of the patients with RTIs. Adjusting for confounders, males experienced 9.8 times greater odds of alcohol related RTIs than females. Compared to 15-24 year-olds, the odds of alcohol consumption was 1.4 times greater among 25-34 year-olds and 1.7 times greater among 35-44 year-olds, adjusting for confounding factors. Patients who were passengers in vehicles other than motorized two-wheelers had 90% reduced odds of an alcohol-related RTI than motorized two-wheeler drivers. Drivers of non-two wheelers, passengers on two-wheelers, and pedestrians did not have significantly different odds of an alcohol-related RTI compared to two-wheeler drivers. Nighttime crashes were associated with nearly a threefold increase in the odds of alcohol consumption. CONCLUSIONS: Given that alcohol was suspected or reported in more than one in six injured ED patients with RTIs, it is clear that alcohol is a serious risk factor for RTIs; this evidence can guide prevention efforts. These findings suggest that evidence-based interventions to reduce drink-driving, such as random breath testing (where law enforcement officials stop drivers on the road to test them for alcohol use), could be more widespread in India. Future studies should assess the effectiveness of greater implementation and enforcement of policies to decrease alcohol's availability to reduce RTIs. PMID- 26260624 TI - Enhancement, ethics and society: towards an empirical research agenda for the medical humanities and social sciences. AB - For some time now, bioethicists have paid close attention to issues associated with 'enhancement'; specifically, the appropriate use and regulation of substances and artefacts understood by some to improve the functioning of human bodies beyond that associated with 'normal' function. Medical humanities scholars (aside from philosophers and lawyers) and social scientists have not been frequent participants in debates around enhancement, but could shine a bright light on the range of dilemmas and opportunities techniques of enhancement are purported to introduce. In this paper, we argue that empirical research into the notion and practice of enhancement is necessary and timely. Such work could fruitfully engage with-and further develop-existing conceptual repertoires within the medical humanities and social sciences in ways that would afford benefit to scholars in those disciplines. We maintain that empirical engagements could also provide important resources to bioethicists seeking to regulate new enhancements in ways that are sensitive to societal context and cultural difference. To this end, we outline an empirical agenda for the medical humanities and social sciences around enhancement, emphasising especially how science and technology studies could bring benefits to-and be benefitted by-research in this area. We also use the example of (pharmaceutical) cognitive enhancement to show how empirical studies of actual and likely enhancement practices can nuance resonant bioethical debates. PMID- 26260625 TI - Preferences for anticoagulation therapy in atrial fibrillation: the patients' view. AB - Since the introduction of new oral anticoagulants (NOACs), besides vitamin-K antagonists, an additional option for stroke prevention of patients with atrial fibrillation (AF) is available. The objective of this study was to assess AF patients' preferences with regard to the attributes of these different treatment options. We conducted a multicenter study among randomly selected physicians. Preferences were assessed by computer-assisted telephone interviews. We used a discrete-choice-experiment (DCE) with four convenience-related treatment dependent attributes (need of bridging: yes/no, interactions with food/nutrition: yes/no, need of INR controls/dose adjustment: yes/no; frequency of intake: once/twice daily) and one comparator attribute (distance to practitioner: <1 km/>15 km). Preferences measured in the interviews were analyzed descriptively and based on a conditional logit regression model. A total of 486 AF patients (age: 73.9 +/- 8.2 years; 43.2 % female; mean CHA2DS2-VASc: 3.7 +/- 1.6; current medication: 48.1 % rivaroxaban, 51.9 % VKA) could be interviewed. Regardless of type of medication, patients significantly preferred the attribute levels (in order of patients' importance) "once daily intake" (Level: once = 1 vs. twice = 0; Coefficient = 0.615; p < 0.001), "bridging necessary" (yes = 1 vs. no = 0; 0.558; p < 0.001), "distance to practitioner of <=1 km (>15 km = 0 vs. <=1 km = 1; 0.494; p < 0.001), "interactions with food/nutrition" (yes = 1 vs. no = 0; 0.332; p < 0.001) and "need of INR controls/dose adjustment" (yes = 1 vs. no = 0; -0.127; p < 0.001). In our analyses, "once daily frequency of intake" was the most important OAC-attribute for patients' choice followed by "no bridging necessary" and "no interactions with food/nutrition". Thus, patients with AF seem to prefer treatment options which are easier to administer. PMID- 26260626 TI - Sexually transmitted infection screening and reproductive health counseling in adolescent renal transplant recipients: Perceptions and practice patterns. A study from the Midwest Pediatric Nephrology Consortium. AB - We wanted to identify practice patterns and perceived barriers among pediatric nephrologists regarding STI screening and reproductive health counseling in adolescent renal transplant recipients. We created an online Likert-scaled survey. Response rate was 54%. The majority (83%) believed STI risk in their patients was similar to or higher than healthy teens. Interestingly, while 67% felt moderately or very confident in asking about sexual activity and counseling about safer sex, only 43% routinely or always inquired about sexual activity, and only 42% routinely or always counseled about safer sex. Fifty-four percent routinely or always discussed contraceptive options and implications of unintentional pregnancy. Fifty-one percent routinely or always referred patients to a gynecologist or adolescent provider for contraception prescription. The most common counseling mechanism was informal discussions in clinic (87%). Ten percent had no mechanism in place. Major barriers included time limitations, adolescents' fear regarding confidentiality, and lack of professional training. This is the first report of perceptions and practice patterns of pediatric nephrologists regarding STI screening and reproductive health counseling. Providers seem to recognize the importance of counseling; however, translation into practice remains low. Professional training in this area and increased encounter time could improve counseling delivery and thereby reduce risk in this population. PMID- 26260627 TI - Region-Specific Alterations of Matrix Metalloproteinase Activity in Multiple System Atrophy. AB - BACKGROUND: MSA is a sporadic progressive neurodegenerative disorder characterized by a variable combination of parkinsonism, cerebellar ataxia, and autonomic dysfunction. The pathological hallmark of MSA is the accumulation of alpha-synuclein aggregates in the cytoplasm of oligodendrocytes along with neuronal loss and neuroinflammation, as well as blood-brain barrier dysfunction and myelin deterioration. Matrix metalloproteinases are zinc-dependent endopeptidases involved in the remodeling of the extracellular matrix, demyelination, and blood-brain barrier permeability. Several lines of evidence indicate a role for these enzymes in various pathological processes, including stroke, multiple sclerosis, Parkinson's, and Alzheimer's disease. METHODS: This study aimed to assess potential alterations of matrix metalloproteinase-1, -2, 3, and -9 expression or activity in MSA postmortem brain tissue. RESULTS: Gelatin zymography revealed increased matrix metalloproteinase-2 activity in the putamen, but not in the frontal cortex, of MSA patients relative to controls. Immunohistochemistry revealed increased number of glial cells positive for matrix metalloproteinase-1, -2, and -3 in the putamen and frontal cortex of MSA patients. Double immunofluorescence revealed that matrix metalloproteinase-2 and 3 were expressed in astrocytes and microglia. Only matrix metalloproteinase-2 colocalized with alpha-synuclein in oligodendroglial cytoplasmic inclusions. CONCLUSION: These results demonstrate widespread alterations of matrix metalloproteinase expression in MSA and a pattern of increased matrix metalloproteinase-2 expression and activity affecting preferentially a brain region severely affected (putamen) over a relatively spared region (frontal cortex). Elevated matrix metalloproteinase expression may thus contribute to the disease process in MSA by promoting blood-brain barrier dysfunction and/or myelin degradation. PMID- 26260628 TI - BAM! Utilizing the frequency of Benign, Atypical and Malignant diagnoses for quality improvement in the histopathologic diagnosis of melanocytic neoplasms. AB - BACKGROUND: Healthcare quality measures are metrics that quantify medical outcomes. There is a need for performance indicators in the diagnosis of melanocytic neoplasms. We sought to determine whether the atypical to malignant diagnosis ratio (AMR) and benign to malignant diagnosis ratio (BMR) could identify differences between practitioners within a group as well as individual diagnostic drift. METHODS: Diagnoses of melanocytic neoplasms from 2013 and 2014 by two dermatopathologists were prospectively subclassified as benign, atypical or malignant and reported on a monthly basis to the pathologists. Case diagnoses of melanocytic neoplasms from 2012 and 2009 were retrospectively subclassified as benign, atypical or malignant for comparison. RESULTS: A total of 33,169 cases were used in this study. Interpathologist AMR and BMR were significantly different. One pathologist demonstrated a significant increase in AMR over time. CONCLUSION: AMR and BMR metrics are potential performance indicators that can measure pathologist uncertainty, identify diagnostic drift and provide a surrogate measure of the relative risk level of laboratory patient populations. If applied to multiple laboratories, AMR and BMR metrics could help inform physicians' choice of dermatopathology laboratory and provide a method for comparative analysis between laboratories. PMID- 26260629 TI - Carers' experiences, needs and preferences during inpatient stroke rehabilitation: a protocol for a systematic review of qualitative studies. AB - BACKGROUND: Large numbers of people provide carer roles for survivors of stroke. Person-centred stroke rehabilitation must consider the perspectives of carers, as stroke affects not only the stroke survivor but also the quality of life and health of the carers. There is little collective knowledge about stroke carers' experiences, needs and preferences during the inpatient stroke rehabilitation process to then inform person-centred service improvements. Our objective is to report and synthesise experiences, needs and preferences of the carers of stroke survivors undergoing rehabilitation in inpatient settings. METHODS/DESIGN: We will conduct a systematic review of qualitative studies using a thematic synthesis methodology. We will follow the Enhancing Transparency in Reporting the Synthesis of Qualitative Research Guidelines (ENTREQ) and search the following databases for relevant articles: MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, Embase, and Web of Science. No language or publication date constraints will be applied. Eligible studies will have to use qualitative methods of data collection and analysis and reported data from the carers of stroke survivors who underwent inpatient stroke rehabilitation. Studies will be eligible for inclusion if they report the experiences, needs and preferences of carers regarding inpatient rehabilitation environments, organisation, care systems, therapeutic interventions, information exchange, carer training, discharge and community service planning and other issues of relevance to their roles as carers. Study selection and assessment of quality will be performed independently by two reviewers. Any disagreement will be resolved by a third reviewer. Data will be extracted by one reviewer, tabled, and checked for accuracy by another reviewer. All text reported in studies' results, discussion and conclusion sections will be entered into the NVivo software for analysis. Extracted texts will be inductively coded independently by two reviewers and analysed in three phases using thematic synthesis. Descriptive and analytical themes will be developed. DISCUSSION: This study is expected to provide new insights into the perspectives of stroke survivors' carers. Increased knowledge about carer perspectives and preferences will inform person-centred improvements in stroke rehabilitation. STUDY REGISTRATION: PROSPERO registration number: CRD42015017315 . PMID- 26260630 TI - Estimating the onset of spring from a complex phenology database: trade-offs across geographic scales. AB - Phenology is an important indicator of ecological response to climate change. Yet, phenological responses are highly variable among species and biogeographic regions. Recent monitoring initiatives have generated large phenological datasets comprised of observations from both professionals and volunteers. Because the observation frequency is often variable, there is uncertainty associated with estimating the timing of phenological activity. "Status monitoring" is an approach that focuses on recording observations throughout the full development of life cycle stages rather than only first dates in order to quantify uncertainty in generating phenological metrics, such as onset dates or duration. However, methods for using status data and calculating phenological metrics are not standardized. To understand how data selection criteria affect onset estimates of springtime leaf-out, we used status-based monitoring data curated by the USA National Phenology Network for 11 deciduous tree species in the eastern USA between 2009 and 2013. We asked, (1) How are estimates of the date of leaf out onset, at the site and regional levels, influenced by different data selection criteria and methods for calculating onset, and (2) at the regional level, how does the timing of leaf-out relate to springtime minimum temperatures across latitudes and species? Results indicate that, to answer research questions at site to landscape levels, data users may need to apply more restrictive data selection criteria to increase confidence in calculating phenological metrics. However, when answering questions at the regional level, such as when investigating spatiotemporal patterns across a latitudinal gradient, there is low risk of acquiring erroneous results by maximizing sample size when using status derived phenological data. PMID- 26260631 TI - dsRNA silencing of an R2R3-MYB transcription factor affects flower cell shape in a Dendrobium hybrid. AB - BACKGROUND: The R2R3-MYB genes regulate pigmentation and morphogenesis of flowers, including flower and cell shape, and therefore have importance in the development of new varieties of orchids. However, new variety development is limited by the long breeding time required in orchids. In this study, we identified a cDNA, DhMYB1, that is expressed during flower development in a hybrid orchid, Dendrobium hybrida (Dendrobium bobby messina X Dendrobium chao phraya) then used the direct application of dsRNA to observe the effect of gene silencing on flower phenotype and floral epidermal cell shape. RESULTS: Flower bud development in the Dendrobium hybrid was characterised into seven stages and the time of meiosis was determined as between stages 3 to 5 when the bud is approximately half of the mature size. Scanning electron microscopy characterisation of adaxial epidermal cells of the flower perianth, showed that the petals and sepals each are divided into two distinct domains based on cell shape and size, while the labellum comprises seven domains. Thirty-two partial cDNA fragments representing R2R3-MYB gene sequences were isolated from D. hybrida. Phylogenetic analysis revealed that nine of the translated sequences were clustered with MYB sequences that are known to be involved in cell shape development and from these, DhMYB1 was selected for full length cDNA cloning and functional study. Direct application of a 430 bp dsRNA from the 3' region of DhMYB1 to emerging orchid flower buds reduced expression of DhMYB1 RNA compared with untreated control. Scanning electron microscopy of adaxial epidermal cells within domain one of the labellum of flowers treated with DhMYB1 dsRNA showed flattened epidermal cells whilst those of control flowers were conical. CONCLUSIONS: DhMYB1 is expressed throughout flower bud development and is involved in the development of the conical cell shape of the epidermal cells of the Dendrobium hybrida flower labellum. The direct application of dsRNA changed the phenotype of floral cells, thus, this technique may have application in floriculture biotechnology. PMID- 26260632 TI - Mechano growth factor E peptide promotes rat bone marrow-derived mesenchymal stem cell migration through CXCR4-ERK1/2. AB - Mechano growth factor (MGF) is a splicing variant of insulin-like growth factor 1 (IGF-1). The unique C-terminal E domain of MGF (MGF-E) makes it distinct from the other variants of IGF-1. Our previous work demonstrated that MGF-25E induces the migration of rat bone marrow-derived mesenchymal stem cells (rMSCs) by altering their mechanical properties, which is accompanied by the activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. However, the relationship between ERK1/2 activation and the change in mechanical properties has not been illustrated. In the present study, we determined that MGF-25E induced the migration of rMSCs by modulating CXCR4 to activate the ERK1/2 pathway. The analysis of the Young's modulus and F-actin remodeling indicated that MGF-25E increased the stiffness and the F-actin polymerization of rMSCs through the activation of the CXCR4-ERK1/2 pathway. For the first time, this study clarified the signaling pathway that regulates the mechanical properties of rMSCs and is responsible for MGF-25E-promoted migration. PMID- 26260633 TI - Author-suggested reviewers - Or the helper's dilemma. PMID- 26260634 TI - Trends in adult exposure to secondhand smoke in vehicles: Findings from the 2009 2012 Canadian Tobacco Use Monitoring Survey. AB - INTRODUCTION: A growing number of jurisdictions have implemented smoke-free vehicles when children are present due to the substantial health effects of secondhand smoke (SHS). Prior studies on the prevalence of SHS exposure in vehicles have mainly focused on adolescents. This study examined the prevalence and socio-demographic correlates of SHS exposure in vehicles among Canadian adults. METHODS: A repeated cross-sectional data on youth and adult data were drawn from the 2009-2012 Canadian Tobacco Use Monitoring Survey (n=58, 195). Multivariable logistic regression analysis was used to examine the socio demographic correlates of exposure to SHS in vehicles. RESULTS: Overall, 19% in 2009 and 18% in 2012 of adults reported SHS exposure in vehicles in the past month. Disparities in the SHS exposure prevalence were observed, with a higher SHS exposure among current smokers, former smokers, males, younger adults, living in a household with smoking-related exposure, and those with less education. The multivariable analyses showed significant associations between socio-demographic characteristics and SHS exposure. Higher odds SHS exposure was found for those younger (aged 20-24, OR=16.27, CI=11.09-23.88; 25-44, OR=6.12, CI=4.14-9.06; 45 64, OR=2.79, CI=1.95-4.02) compared to those aged 65 and over. Likewise, those with less education had greater odds of SHS exposure. CONCLUSIONS: Findings suggest that adults SHS exposure is high, especially for young adults and those with less education. Adult passengers may need protection from SHS given that no level of SHS exposure is safe. PMID- 26260635 TI - Using species sensitivity distribution approach to assess the risks of commonly detected agricultural pesticides to Australia's tropical freshwater ecosystems. AB - To assess the potential impacts of agricultural pesticides on tropical freshwater ecosystems, the present study developed temperature-specific, freshwater species protection concentrations (i.e., ecotoxicity threshold values) for 8 pesticides commonly detected in Australia's tropical freshwaters. Because relevant toxicity data for native tropical freshwater species to assess the ecological risks were mostly absent, scientifically robust toxicity data obtained at >=20 degrees C were used for ecologically relevant taxonomic groups representing primary producers and consumers. Species sensitivity distribution (SSD) curves were subsequently generated for predicted chronic exposure using Burrlioz 2.0 software with mixed chronic and converted acute data relevant to exposure conditions at >=20 degrees C. Ecotoxicity threshold values for tropical freshwater ecosystem protection were generated for ametryn, atrazine, diuron, metolachlor, and imidacloprid (all moderate reliability), as well as simazine, hexazinone, and tebuthiuron (all low reliability). Using these SSD curves, the retrospective risk assessments for recently reported pesticide concentrations highlight that the herbicides ametryn, atrazine, and diuron are of major concern for ecological health in Australia's tropical freshwater ecosystems. The insecticide imidacloprid also appears to pose an emerging threat to the most sensitive species in tropical freshwater ecosystems. The exposed temperature-specific approach may be applied to develop water quality guideline values for other environmental contaminants detected in tropical freshwater ecosystems until reliable and relevant toxicity data are generated using representative native species. PMID- 26260636 TI - Two distinct conformational states of Mycobacterium tuberculosis virulent factor early secreted antigenic target 6 kDa are behind the discrepancy around its biological functions. AB - Early secreted antigenic target 6 kDa (ESAT-6) and culture filtrate protein 10 kDa (CFP-10) are complex proteins secreted by Mycobacterium tuberculosis that play a major role in the pathogenesis of tuberculosis. However, studies focusing on the biological functions of ESAT-6 led to discordant results and the role of ESAT-6 remains controversial. In the present study, we aim to address a potential explanation for this discrepancy and to highlight the physiological impact of two conformational states of ESAT-6. Analysis of a recombinant form of ESAT-6 by native gel electrophoresis, size exclusion chromatography and CD spectroscopy revealed that ESAT-6 forms dimers/multimers with higher molecular weight, which disappeared under the action of the detergent amidosulfobetaine-14 (ASB), giving rise to another conformational state of the protein. NMR has further indicated that ASB-treated versus nontreated ESAT-6 adopted distinct structural forms but with no well defined tertiary structure. However, protein-protein docking analysis favored a dimeric state of ESAT-6. Interestingly, the two preparations presented opposing effects on mycobacterial infectivity, as well as macrophage survival, interferon-gamma secretion and membrane pore formation. Thereafter, we generated a recombinant form of the physiological heterodimer ESAT-6/CFP-10 that ASB was also able to dissociate and which showed functions similar to those of ESAT-6 dimers/multimers. Our data suggest that, in the absence of CFP-10, the hydrophobic regions of the ESAT-6 can form dimers/multimers, mimicking the ESAT 6/CFP-10 heterodimer, whereas their dissociation generates a protein presenting entirely different activities. Overall, the present study clarifies the intriguing divergences between reports that could be attributed to the ESAT-6 oligomeric state and sheds light on its importance for a better comprehension of the physiopathology of tuberculosis. PMID- 26260638 TI - Demanding New Solutions. PMID- 26260637 TI - Physiological and biochemical plasticity of Lepidium latifolium as 'sleeper weed' in Western Himalayas. AB - To understand the spread of native populations of Lepidium latifolium growing in different altitudes in Ladakh region of Western Himalayas, photosynthetic and fluorescence characteristics were evaluated in relation to their micro environment. Three sites representing sparsely populated (SPS), moderately populated (MPS) and densely populated site (DPS) were selected. Results showed that the DPS had higher photosynthetic accumulation than MPS and SPS. The higher transpiration rate at DPS despite lower vapor pressure deficit and higher relative humidity suggest the regulation of its leaf temperature by evaporative cooling. Intrinsic soil parameters such as water holding capacity and nutrient availability also play crucial role in higher biomass here. The quantum efficiency of PSII photochemistry (Fv/Fm, non-photochemical quenching (NPQ), PhiPSII) and light curve at various PPFDs suggests better light harvesting potential and light compensation point at DPS than the other two sites. Concomitantly, plants at SPS had significantly higher lipid peroxidation, suggesting a stressful environment, and higher induction of antioxidative enzymes. Metabolic content of reduced glutathione also suggests an efficient mechanism in DPS and MPS than SPS. High light intensities at MPS are managed by specialized contrive of carotenoid pigments and PsbS gene product. Large pool of violaxanthin and lutein plays an important role in this response. It is suggested that L. latifolium is present as 'sleeper weed' that has inherent biochemical plasticity involving multiple processes in Western Himalayas. Its potential spread is linked to site-specific micro-environment, whereby, it prefers flat valley bottoms with alluvial fills having high water availability, and has little or no altitudinal effect. PMID- 26260639 TI - Niche Markets: Filling Gaps with Expertise, Ingenuity. AB - Niche markets present opportunities for pharmacists to expand their presence and increase the demand for their services. These practitioners have clinical skills that they can use to improve medication management, reduce medication-related problems and hospitalizations, and enhance the quality of life for patients in specialty areas such as menopause management and women's health, hospice and palliative care, and pediatric long-term care. PMID- 26260640 TI - Identification, Treatment, and Prevention of Calcium-Alkali Syndrome in Elderly Patients. AB - OBJECTIVE: To guide pharmacists in identifying geriatric patients at risk, and providing education on the prevention and monitoring of calcium-alkali syndrome. DATA SOURCES: Searches of MEDLINE and Google Scholar (1990-February 2014). Search terms included milk-alkali syndrome, calcium-alkali syndrome, hypercalcemia, calcium carbonate, geriatric patients, and elderly patients. STUDY SELECTION: Published articles and case reports were chosen for inclusion to provide evidence based treatment and management of calcium-alkali syndrome in elderly patients. DATA SYNTHESIS: There are not many observational, prospective, and randomized studies focusing on treating calcium-alkali syndrome in geriatric patients. Information was extrapolated from four case-based studies focusing on geriatric individuals affected by calcium-alkali syndrome. CONCLUSION: Conventional treatments used in the case studies were shown to be effective in treating geriatric patients affected by calcium-alkali syndrome. Use of case studies affects generalization and specific treatment and prevention strategies in the geriatric patient population. While more robust studies are still required to display definite treatments for geriatric patients, the case studies demonstrated resolution in health outcomes with conventional treatments. The use of optimized adult treatments and prevention strategies effectively improves health conditions in geriatric patients affected or susceptible to calcium-alkali syndrome. PMID- 26260641 TI - A Case of an Older Adult Patient and Drugs Associated with Serotonin Syndrome. AB - Older adults have increased risk for depression, and the use of selective serotonin reuptake inhibitors (SSRIs) is common. Serotonin syndrome is a potential adverse event associated with the use of SSRIs, the combination of SSRIs and trazodone, and the combination of SSRIs and linezolid. Pharmacists are ideal for assessing older adult drug regimens and recognizing potential drug interactions associated with proserotonergic drugs and alleviating adverse events for patients. PMID- 26260642 TI - The Impact of Pharmacist Interventions on Herpes Zoster Vaccination Rates. AB - The Centers for Disease Control and Prevention found that in 2010 only 14.4% of people in the United States who are appropriate candidates received the herpes zoster (shingles) vaccine. This manuscript highlights recent studies that investigate how pharmacists can help improve vaccination rates of herpes zoster in the geriatric population. Research has demonstrated that face-to-face interaction, education, and outreach by pharmacists in the community can help improve rates of herpes zoster vaccination. Having pharmacists take time to talk with patients about the vaccine was shown to have a positive impact on vaccine rates. When face-to-face interactions are not feasible, promotional materials such as newspaper advertisements, flyers, and personalized letters were also found to have a beneficial impact. Pharmacists should consider ways to increase awareness of vaccinations and directly encourage their patients to be vaccinated. PMID- 26260643 TI - Changes in Mood in New Enrollees at a Program of All-Inclusive Care for the Elderly. AB - OBJECTIVES: To examine changes in mood after nine months of enrollment in a Program of All-Inclusive Care for the Elderly (PACE). DESIGN: Cohort study. SETTING: Alexian Brothers PACE, St. Louis, Missouri. PARTICIPANTS: Newly enrolled patients 55 years of age and older, living in the PACE service area, eligible for nursing facility care and able to live safely in the community, with continuous care, for at least nine months (N = 182). MAIN OUTCOME MEASURES: Geriatric Depression Scale (GDS)-15 score at the pre-admission evaluation (PAE) and the nine-month evaluation (9ME). RESULTS: Of the 182 patients evaluated, 27% (n = 49) met the definition of depression as defined by the GDS-15 score of >= 6 at the PAE. At the 9ME, only 11% of patients met the depression criteria (P < 0.001). Of the patients who met the criteria for depression at the PAE, 80% of patients (n = 39) no longer met these criteria at the 9ME (P = 0.029). Similar findings were observed by age, gender, and race. Greater improvement was observed among those who were depressed at the PAE; the depressed cohort improved by 5.0 points (P < 0.001) on the GDS-15 scale from the PAE to the 9ME, whereas the nondepressed cohort improved by 0.6 points (P = 0.003). CONCLUSION: The use of PACE as an alternative intervention may be a good option to improve mood in older adults. PMID- 26260644 TI - What Does Provider Status Mean for Pharmacists? PMID- 26260645 TI - Implementation and validation of a risk stratification method at The Ottawa Hospital to guide thromboprophylaxis in ambulatory cancer patients at intermediate-high risk for venous thrombosis. AB - BACKGROUND: Cancer patients have a significantly higher risk of developing a venous thromboembolism (VTE) compared to non-cancer patients and yet studies suggest VTE risk among ambulatory cancer patients varies widely. Recently, predictive models capable of risk-stratifying a broad range of ambulatory cancer outpatients have been developed. Using the Khorana model a score of 2 was intermediate-high risk for VTE as reported by Ay and colleagues. However, validation in a broader population and methods to implement this model seamlessly into clinical practice are lacking. OBJECTIVE: To create and assess the feasibility of an innovative computerized Care Process Management System (CPMS) that would automatically access electronic medical records to calculate in real time the risk of VTE in patients with active cancer using an established VTE risk scoring system. METHODS: A prospective observational study of all newly referred cancer patients at the Ottawa Regional Cancer Center, the sole cancer care provider for 1.2 million inhabitants, was conducted. RESULTS: 699 new referrals were determined to have a cancer diagnosis for the first time as identified by the computer software and qualified for our study and 580 were eligible. In total 25% had intermediate-high risk for VTE and during the 3-month follow up period, 16 of the 143 (11%) developed a VTE which further validates the Khorana model for identifying intermediate-high risk patients. Of the 437 patients in the low risk group 19 (4%) developed a VTE. CONCLUSION: Newly diagnosed cancer patients can be readily stratified into intermediate-high and low risk of VTE using our novel CPMS system. This innovative tool can be used to facilitate customized management decisions regarding VTE prophylaxis for intermediate-high risk patients based their individual risk factors. PMID- 26260646 TI - Factors related to accidental dural puncture in epidural anesthesia patients. AB - OBJECTIVES: Accidental dural puncture (ADP) is known as a complication of epidural anesthesia. Although puncture site and advanced age have been reported to increase the risk of ADP, all related factors have not been fully investigated. We retrospectively investigated factors related to ADP in patients undergoing surgery. METHODS: We reviewed the records of 4107 patients who received epidural anesthesia or combined spinal-epidural anesthesia from April 2010 to March 2013 at our institution. We defined ADP as cases in which cerebrospinal fluid was obviously discharged during puncture and excluded cases in which the epidural catheter was suspected to be inserted into subarachnoid space. We investigated patient background including age, sex, height, body weight, body mass index, vertebral level of puncture site, and presence of ADP, with Student t test, a chi(2) test, and multivariable logistic regression analysis used for statistical tests and significance set at P < .05. RESULTS: Twenty (0.49%) of our patients had ADP. Factors significantly associated were punctures in the 10th-12th thoracic intervertebral (P = .01; odds ratio [OR], 5.19; 95% confidential interval [95% CI], 1.41-19.14) and first to third lumbar intervertebral (P = .03; OR, 5.45; 95% CI, 1.23-24.12) spaces and age (per 1-year increase, P < .01; OR, 1.04; 95% CI, 1.01-1.07). DISCUSSION: Accidental dural puncture occurred in 0.49% of all surgical patients undergoing epidural anesthesia and was significantly related to those who received a puncture in lower thoracic and lumbar intervertebral spaces, whereas age was also an independent factor. PMID- 26260647 TI - Drug-induced immune-mediated thrombocytopenia in the intensive care unit. AB - A 62-year-old woman with prosthetic mitral valve was admitted for explant of an infected prosthetic knee. Perioperatively, she was bridged with heparin and started on empiric vancomycin and piperacillin-tazobactam. Platelet counts dropped precipitously within 2 days reaching a nadir of 6000/MUL, without any bleeding. Decline persisted despite substituting heparin with bivalirudin. Antiplatelet factor 4 and anti-PLA1 antigen were negative. Schistocytes were absent. Antibiotics were substituted with daptomycin for suspected drug-induced thrombocytopenia. Pulse dose of intravenous immunoglobulin was initiated with rapid normalization of platelet count. She tested positive for IgG antiplatelet antibodies to vancomycin and piperacillin-tazobactam thereby confirming the diagnosis. Drug-induced immune-mediated thrombocytopenia is an underrecognized cause of thrombocytopenia in the intensive care units. Clinicians should be cognizant of this entity, and a definitive diagnosis should be sought if feasible. PMID- 26260648 TI - Anesthesia in a patient with dyskeratosis congenita presenting for urgent subtotal gastrectomy. AB - Dyskeratosis congenita is a rare and complex congenital disease that may complicate surgical treatment and impact anesthetic care. We present the perioperative management of a patient with severe pancytopenia, respiratory dysfunction, and oral leukoplakia who presented for urgent surgery for removal of a gastric hemorrhagic malignant tumor. Important issues in the management of this patient include choice of anesthetic technique, correction of pancytopenia (thrombocytopenia in particular), judicious perioperative fluid management to avoid dilutional coagulopathy, antibiotic prophylaxis, and strict aseptic technique. Careful management of a potentially difficult airway and a higher likelihood of respiratory insufficiency further complicate patient care. Knowledge of this rare disease process and its potential impact on anesthetic management is paramount for safe perioperative patient care. PMID- 26260649 TI - Imaging malignant melanoma with (18)F-5-FPN. AB - PURPOSE: Radiolabelled benzamides are attractive candidates for targeting melanoma because they bind to melanin and exhibit high tumour uptake and retention. (18)F-5-Fluoro-N-(2-[diethylamino]ethyl)picolinamide ((18)F-5-FPN), a benzamide analogue, was prepared and its pharmacokinetics and binding affinity evaluated both in vitro and in vivo to assess its clinical potential in the diagnosis and staging of melanoma. METHODS: (18)F-5-FPN was prepared and purified. Its binding specificity was measured in vitro in two different melanoma cell lines, one pigmented (B16F10 cells) and one nonpigmented (A375m cells), and in vivo in mice xenografted with the same cell lines. Dynamic and static PET images using (18)F-5-FPN were obtained in the tumour-bearing mice, and the static images were also compared with those acquired with (18)F-FDG. PET imaging with (18)F-5-FPN was also performed in B16F10 tumour-bearing mice with lung metastases. RESULTS: (18)F-5-FPN was successfully prepared with radiochemical yields of 5 - 10 %. Binding of (18)F-5-FPN to B16F10 cells was much higher than to A375m cells. On dynamic PET imaging B16F10 tumours were visible about 1 min after injection of the tracer, and the uptake gradually increased over time. (18)F-5-FPN was rapidly excreted via the kidneys. B16F10 tumours were clearly visible on static images acquired 1 and 2 h after injection, with high uptake values of 24.34 +/- 6.32 %ID/g and 16.63 +/- 5.41 %ID/g, respectively, in the biodistribution study (five mice). However, there was no visible uptake by A375m tumours. (18)F-5-FPN and (18)F-FDG PET imaging were compared in B16F10 tumour xenografts, and the tumour-to-background ratio of (18)F-5-FPN was ten times higher than that of (18)F-FDG (35.22 +/- 7.02 vs. 3.29 +/- 0.53, five mice). (18)F-5-FPN PET imaging also detected simulated lung metastases measuring 1 - 2 mm. CONCLUSION: (18)F-5-FPN specifically targeted melanin in vitro and in vivo with high retention and affinity and favourable pharmacokinetics. (18)F-5-FPN may be an ideal molecular probe for melanoma diagnosis and staging. PMID- 26260651 TI - Molecular imaging of glutamate-carboxypeptidase II (prostate-specific membrane antigen) in malignant epithelioid hemangioendothelioma. PMID- 26260650 TI - Amyloid imaging in cognitively normal older adults: comparison between (18)F flutemetamol and (11)C-Pittsburgh compound B. AB - PURPOSE: Preclinical, or asymptomatic, Alzheimer's disease (AD) refers to the presence of positive AD biomarkers in the absence of cognitive deficits. This research concept is being applied to define target populations for clinical drug development. In a prospective community-recruited cohort of cognitively intact older adults, we compared two amyloid imaging markers within subjects: (18)F flutemetamol and (11)C-Pittsburgh compound B (PIB). METHODS: In 32 community recruited cognitively intact older adults aged between 65 and 80 years, we determined the concordance between binary classification based on (18)F flutemetamol versus (11)C-PIB according to semiquantitative assessment (standardized uptake value ratio in composite cortical volume, SUVRcomp) and, alternatively, according to visual reads. We also determined the correlation between (18)F-flutemetamol and (11)C-PIB SUVR and evaluated how this was affected by the reference region chosen (cerebellar grey matter versus pons) and the use of partial volume correction (PVC) in this population. RESULTS: Binary classification based on semiquantitative assessment was concordant between (18)F flutemetamol and (11)C-PIB in 94 % of cases. Concordance of blinded binary visual reads between tracers was 84 %. The Spearman correlation between (18)F flutemetamol and (11)C-PIB SUVRcomp with cerebellar grey matter as reference region was 0.84, with a slope of 0.98. Correlations in neocortical regions were significantly lower with the pons as reference region. PVC improved the correlation in striatum and medial temporal cortex. CONCLUSION: For the definition of preclinical AD based on (18)F-flutemetamol, concordance with (11)C PIB was highest using semiquantitative assessment with cerebellar grey matter as reference region. PMID- 26260652 TI - Lineage-Specific Patterns of Genome Deterioration in Obligate Symbionts of Sharpshooter Leafhoppers. AB - Plant sap-feeding insects (Hemiptera) rely on obligate bacterial symbionts that provision nutrients. Some of these symbionts are ancient and have evolved tiny genomes, whereas others are younger and retain larger, dynamic genomes. Baumannia cicadellinicola, an obligate symbiont of sharpshooter leafhoppers, is derived from a relatively recent symbiont replacement. To better understand evolutionary decay of genomes, we compared Baumannia from three host species. A newly sequenced genome for Baumannia from the green sharpshooter (B-GSS) was compared with genomes of Baumannia from the blue-green sharpshooter (B-BGSS, 759 kilobases [kb]) and from the glassy-winged sharpshooter (B-GWSS, 680 kb). B-GSS has the smallest Baumannia genome sequenced to date (633 kb), with only three unique genes, all involved in membrane function. It has lost nearly all pathways involved in vitamin and cofactor synthesis, as well as amino acid biosynthetic pathways that are redundant with pathways of the host or the symbiotic partner, Sulcia muelleri. The entire biosynthetic pathway for methionine is eliminated, suggesting that methionine has become a dietary requirement for hosts. B-GSS and B-BGSS share 33 genes involved in bacterial functions (e.g., cell division, membrane synthesis, metabolite transport, etc.) that are lost from the more distantly related B-GWSS and most other tiny genome symbionts. Finally, pairwise divergence estimates indicate that B-GSS has experienced a lineage-specific increase in substitution rates. This increase correlates with accelerated protein level changes and widespread gene loss. Thus, the mode and tempo of genome reduction vary widely among symbiont lineages and result in wide variation in metabolic capabilities across hosts. PMID- 26260653 TI - Impact of Parental Bos taurus and Bos indicus Origins on Copy Number Variation in Traditional Chinese Cattle Breeds. AB - Copy number variation (CNV) is an important component of genomic structural variation and plays a role not only in evolutionary diversification but also in domestication. Chinese cattle were derived from Bos taurus and Bos indicus, and several breeds presumably are of hybrid origin, but the evolution of CNV regions (CNVRs) has not yet been examined in this context. Here, we of CNVRs, mtDNA D loop sequence variation, and Y-chromosomal single nucleotide polymorphisms to assess the impact of maternal and paternal B. taurus and B. indicus origins on the distribution of CNVRs in 24 Chinese domesticated bulls. We discovered 470 genome-wide CNVRs, only 72 of which were shared by all three Y-lineages (B. taurus: Y1, Y2; B. indicus: Y3), whereas 265 were shared by inferred taurine or indicine paternal lineages, and 228 when considering their maternal taurine or indicine origins. Phylogenetic analysis uncovered eight taurine/indicine hybrids, and principal component analysis on CNVs corroborated genomic exchange during hybridization. The distribution patterns of CNVRs tended to be lineage-specific, and correlation analysis revealed significant positive or negative co-occurrences of CNVRs across lineages. Our study suggests that CNVs in Chinese cattle partly result from selective breeding during domestication, but also from hybridization and introgression. PMID- 26260654 TI - Novel SIL1 mutations cause cerebellar ataxia and atrophy in a French-Canadian family. AB - Two French-Canadian sibs with cerebellar ataxia and dysarthria were seen in our neurogenetics clinic. The older brother had global developmental delay and spastic paraplegia. Brain MRIs from these two affected individuals showed moderate to severe cerebellar atrophy. To identify the genetic basis for their disease, we conducted a whole exome sequencing (WES) investigation using genomic DNA prepared from the affected sibs and their healthy father. We identified two mutations in the SIL1 gene, which is reported to cause Marinesco-Sjogren syndrome. This study emphasizes how the diagnosis of patients with ataxic gait and cerebellar atrophy may benefit from WES to identify the genetic cause of their condition. PMID- 26260655 TI - Levels and potential health risks of mercury in prescription, non-prescription medicines and dietary supplements in Poland. AB - Determination of mercury is important in the case of pharmaceuticals for which the European Union regulations have not defined the maximum permissible concentration of this metal. The aim of the study was to determine the levels of mercury in the following groups of drugs (n = 119): analgesics, diuretics, cardiacs, antihypertensives, anti-influenza, antibiotics, anti-allergics, tranquilizers, antibacterials and in dietary supplements (n = 33) available on the Polish market. Mercury was analyzed using cold vapor atomic fluorescence spectrometry CV-AFS. Its content in the samples varied in the range of 0.9-476.1 ng g(-1). Higher mercury concentrations were reported for prescription drugs (Rx): 0.9-476.1 ng g(-1) (median: 7.4 ng g(-1)), lower--for non-prescription medicines (OTC): 1.2-45.8 ng g(-1) (median: 6.0 ng g(-1)). In the analyzed dietary supplements the concentrations were: 0.9-16.7 ng g(-1) (median: 5.9 ng g( 1)). On the basis of the information contained in the leaflet accompanying the medicine, a daily dose of mercury taken into the body with an analyzed medicament was estimated and the health risk posed by using such medicines was assessed. The study indicates that it is justified to carry out measurements of mercury in pharmaceuticals due to its high, potentially harmful. PMID- 26260656 TI - Health Canada's use of priority review status for drugs for unmet needs. AB - The processes for granting priority review status to new drug submissions in Canada and the United States are not exactly the same, but reasonable concordance should be expected since the selection criteria are similar in the two countries. This study compared new therapeutic drugs approved by both Health Canada and the Food and Drug Administration (FDA) between 2000 and 2014 to evaluate concordance on priority review status. New therapeutic drugs approved in both countries totalled 301; 86 (28.6%) and 136 (45.2%) were given priority review status in Canada and the United States, respectively, with 73 (24.3%) in both. Sensitivity and specificity were 53.7% and 92.1%. Overall concordance on review type was 74.8%. kappa was 0.47 indicating moderate agreement. Agreement on review type was >70% for all drugs, except oncology therapies. Broad agreement exists between Health Canada and the FDA on drugs that should not have priority review status. Concordance on drugs that should have this status was generally satisfactory and, for critical drugs, was high. Agreement would improve if more oncology drugs received priority review status in Canada. Despite a higher number of drugs receiving priority review status in the United States, there is reasonable concordance between the two countries. PMID- 26260657 TI - Neurodegenerative disease: Changes in brain phosphodiesterase 10A levels in neurodegenerative basal ganglia disorders. PMID- 26260658 TI - Alzheimer disease: Insulin resistance could be linked to risk of AD via reduced glucose uptake. PMID- 26260660 TI - Bilateral spontaneous salivary otorrhoea: Case report and a review of the literature. AB - Spontaneous salivary otorrhoea is an extremely rare clinical entity. Most of the times, salivary otorrhoea results from various forms of trauma. It has also been attributed to the patent foramen of Huschke, and fissures of Santorini. Here, we present a rare case of an 8 year old child presenting with salivary discharge from both the ears. The diagnosis was established on the basis of biochemical and radiological investigations. The patient was managed by surgical exploration and ligation of the fistulous tract. PMID- 26260659 TI - Prospects of immune checkpoint modulators in the treatment of glioblastoma. AB - Glioblastoma is the most common primary brain tumour in adults. Prognosis is poor: even with the current gold-standard first-line treatment-maximal safe resection and combination of radiotherapy with temozolomide chemotherapy-the median overall survival time is only approximately 15-17 months, because the tumour recurs in virtually all patients, and no commonly accepted standard treatment for recurrent disease exists. Several targeted agents have failed to improve patient outcomes in glioblastoma. Immunotherapy with immune checkpoint inhibitors such as ipilimumab, nivolumab, and pembrolizumab has provided relevant clinical improvements in other advanced tumours for which conventional therapies have had limited success, making immunotherapy an appealing strategy in glioblastoma. This Review summarizes current knowledge on immune checkpoint modulators and evaluates their potential role in glioblastoma on the basis of preclinical studies and emerging clinical data. Furthermore, we discuss challenges that need to be considered in the clinical development of drugs that target immune checkpoint pathways in glioblastoma, such as specific properties of the immune system in the CNS, issues with radiological response assessment, and potential interactions with established and emerging treatment strategies. PMID- 26260661 TI - A speech reception in noise test for preschool children (the Galker-test): Validity, reliability and acceptance. AB - PURPOSE: This study evaluates initial validity and reliability of the "Galker test of speech reception in noise" developed for Danish preschool children suspected to have problems with hearing or understanding speech against strict psychometric standards and assesses acceptance by the children. METHODS: The Galker test is an audio-visual, computerised, word discrimination test in background noise, originally comprised of 50 word pairs. Three hundred and eighty eight children attending ordinary day care centres and aged 3-5 years were included. With multiple regression and the Rasch item response model it was examined whether the total score of the Galker test validly reflected item responses across subgroups defined by sex, age, bilingualism, tympanometry, audiometry and verbal comprehension. RESULTS: A total of 370 children (95%) accepted testing and 339 (87%) completed all 50 items. The analysis showed that 35 items fitted the Rasch model. Reliability was 0.75 before and after exclusion of the 15 non-fitting items. In the stepwise linear regression model age group of children could explain 20% of the variation in Galker-35-score, sex 1%, second language at home 4%, tympanometry in best ear 2%, and parental education another 2%. Other variable did not reach significance. CONCLUSION: The Galker-35 was well accepted by children down to the age of 3 years and results indicate that the scale represents construct valid and reliable measurement. PMID- 26260663 TI - Challenges to addressing obesity for Maori in Aotearoa/New Zealand. PMID- 26260662 TI - Heteropentanuclear Oxalato-Bridged nd-4f (n=4, 5) Metal Complexes with NO Ligand: Synthesis, Crystal Structures, Aqueous Stability and Antiproliferative Activity. AB - A series of heteropentanuclear oxalate-bridged Ru(NO)-Ln (4d-4f) metal complexes of the general formula (nBu4N)5[Ln{RuCl3(MU-ox)(NO)}4], where Ln=Y (2), Gd (3), Tb (4), Dy (5) and ox=oxalate anion, were obtained by treatment of (nBu4N)2[RuCl3(ox)(NO)] (1) with the respective lanthanide salt in 4:1 molar ratio. The compounds were characterized by elemental analysis, IR spectroscopy, electrospray ionization (ESI) mass spectrometry, while 1, 2, and 5 were in addition analyzed by X-ray crystallography, 1 by Ru K-edge XAS and 1 and 2 by (13)C NMR spectroscopy. X-ray diffraction showed that in 2 and 5 four complex anions [RuCl3(ox)(NO)](2-) are coordinated to Y(III) and Dy(III), respectively, with formation of [Ln{RuCl3(MU-ox)(NO)}4](5-) (Ln=Y, Dy). While Y(III) is eight coordinate in 2, Dy(III) is nine-coordinate in 5, with an additional coordination of an EtOH molecule. The negative charge is counterbalanced by five nBu4N(+) ions present in the crystal structure. The stability of complexes 2 and 5 in aqueous medium was monitored by UV/Vis spectroscopy. The antiproliferative activity of ruthenium-lanthanide complexes 2-5 were assayed in two human cancer cell lines (HeLa and A549) and in a noncancerous cell line (MRC-5) and compared with those obtained for the previously reported Os(NO)-Ln (5d-4f) analogues (nBu4N)5[Ln{OsCl3(ox)(NO)}4] (Ln=Y (6), Gd (7), Tb (8), Dy (9)). Complexes 2-5 were found to be slightly more active than 1 in inhibiting the proliferation of HeLa and A549 cells, and significantly more cytotoxic than 5d-4f metal complexes 6-9 in terms of IC50 values. The highest antiproliferative activity with IC50 values of 20.0 and 22.4 MUM was found for 4 in HeLa and A549 cell lines, respectively. These cytotoxicity results are in accord with the presented ICP-MS data, indicating five- to eightfold greater accumulation of ruthenium versus osmium in human A549 cancer cells. PMID- 26260664 TI - Adaptive emotional memory: the key hippocampal-amygdalar interaction. AB - For centuries philosophical and clinical studies have emphasized a fundamental dichotomy between emotion and cognition, as, for instance, between behavioral/emotional memory and explicit/representative memory. However, the last few decades cognitive neuroscience have highlighted data indicating that emotion and cognition, as well as their underlying neural networks, are in fact in close interaction. First, it turns out that emotion can serve cognition, as exemplified by its critical contribution to decision-making or to the enhancement of episodic memory. Second, it is also observed that reciprocally cognitive processes as reasoning, conscious appraisal or explicit representation of events can modulate emotional responses, like promoting or reducing fear. Third, neurobiological data indicate that reciprocal amygdalar-hippocampal influences underlie such mutual regulation of emotion and cognition. While supporting this view, the present review discusses experimental data, obtained in rodents, indicating that the hippocampal and amygdalar systems not only regulate each other and their functional outcomes, but also qualify specific emotional memory representations through specific activations and interactions. Specifically, we review consistent behavioral, electrophysiological, pharmacological, biochemical and imaging data unveiling a direct contribution of both the amygdala and hippocampal-septal system to the identification of the predictor of a threat in different situations of fear conditioning. Our suggestion is that these two brain systems and their interplay determine the selection of relevant emotional stimuli, thereby contributing to the adaptive value of emotional memory. Hence, beyond the mutual quantitative regulation of these two brain systems described so far, we develop the idea that different activations of the hippocampus and amygdala, leading to specific configurations of neural activity, qualitatively impact the formation of emotional memory representations, thereby producing either adaptive or maladaptive fear memories. PMID- 26260665 TI - Early-life adversity programs emotional functions and the neuroendocrine stress system: the contribution of nutrition, metabolic hormones and epigenetic mechanisms. AB - Clinical and pre-clinical studies have shown that early-life adversities, such as abuse or neglect, can increase the vulnerability to develop psychopathologies and cognitive decline later in life. Remarkably, the lasting consequences of stress during this sensitive period on the hypothalamic-pituitary-adrenal axis and emotional function closely resemble the long-term effects of early malnutrition and suggest a possible common pathway mediating these effects. During early-life, brain development is affected by both exogenous factors, like nutrition and maternal care as well as by endogenous modulators including stress hormones. These elements, while mostly considered for their independent actions, clearly do not act alone but rather in a synergistic manner. In order to better understand how the programming by early-life stress takes place, it is important to gain further insight into the exact interplay of these key elements, the possible common pathways as well as the underlying molecular mechanisms that mediate their effects. We here review evidence that exposure to both early-life stress and early-life under-/malnutrition similarly lead to life-long alterations on the neuroendocrine stress system and modify emotional functions. We further discuss how the different key elements of the early-life environment interact and affect one another and next suggest a possible role for the early-life adversity induced alterations in metabolic hormones and nutrient availability in shaping later stress responses and emotional function throughout life, possibly via epigenetic mechanisms. Such knowledge will help to develop intervention strategies, which gives the advantage of viewing the synergistic action of a more complete set of changes induced by early-life adversity. PMID- 26260666 TI - Magnetic resonance imaging study in a normal Bengal tiger (Panthera tigris) stifle joint. AB - BACKGROUND: The purpose of this study was to describe the normal appearance of the bony and soft tissue structures of the stifle joint of a Bengal tiger (Panthera tigris) by low-field magnetic resonance imaging (MRI), and the use of gross anatomical dissections performed as anatomical reference. A cadaver of a mature female was imaged by MRI using specific sequences as the Spin-echo (SE) T1 weighting and Gradient-echo (GE) STIR T2-weighting sequences in sagittal, dorsal and transverse planes, with a magnet of 0.2 Tesla. The bony and articular structures were identified and labelled on anatomical dissections, as well as on the magnetic resonance (MR) images. RESULTS: MR images showed the bone, articular cartilage, menisci and ligaments of the normal tiger stifle. SE T1-weighted sequence provided excellent resolution of the subchondral bones of the femur, tibia and patella compared with the GE STIR T2-weighted MR images. Articular cartilage and synovial fluid were visualised with high signal intensity in GE STIR T2-weighted sequence, compared with SE T1-weighted sequence where they appeared with intermediate intensity signal. Menisci and ligaments of the stifle joint were visible with low signal intensity in both sequences. The infrapatellar fat pad was hyperintense on SE T1-weighted images and showed low signal intensity on GE STIR T2-weighted images. CONCLUSIONS: MRI provided adequate information of the bony and soft tissues structures of Bengal tiger stifle joints. This information can be used as initial anatomic reference for interpretation of MR stifle images and to assist in the diagnosis of diseases of this region. PMID- 26260667 TI - Bias in estimates of alcohol use among older people: selection effects due to design, health, and cohort replacement. AB - BACKGROUND: There is a growing awareness of the need to include the oldest age groups in the epidemiological monitoring of alcohol consumption. This poses a number of challenges and this study sets out to examine the possible selection effects due to survey design, health status, and cohort replacement on estimates of alcohol use among the oldest old. METHODS: Analyses were based on three repeated cross-sectional interview surveys from 1992, 2002 and 2011, with relatively high response rates (86 %). The samples were nationally representative of the Swedish population aged 77+ (total n = 2022). Current alcohol use was assessed by the question "How often do you drink alcoholic beverages, such as wine, beer or spirits?" Alcohol use was examined in relation to survey design (response rate, use of proxy interviews and telephone interviews), health (institutional living, limitations with Activities of Daily Living and mobility problems) and birth cohort (in relation to age and period). Two outcomes were studied using binary and ordered logistic regression; use of alcohol and frequency of use among alcohol users. RESULTS: Higher estimates of alcohol use, as well as more frequent use, were associated with lower response rates, not using proxy interviews and exclusion of institutionalized respondents. When adjusted for health, none of these factors related to the survey design were significant. Moreover, the increase in alcohol use during the period was fully explained by cohort replacement. This cohort effect was also at least partially confounded by survey design and health effects. Results were similar for both outcomes. CONCLUSIONS: Survey non-participation in old age is likely to be associated with poor health and low alcohol consumption. Failure to include institutionalized respondents or those who are difficult to recruit is likely to lead to an overestimation of alcohol consumption, whereas basing prevalence on older data, at least in Sweden, is likely to underestimate the alcohol use of the oldest old. Trends in alcohol consumption in old age are highly sensitive for cohort effects. When analysing age-period-cohort effects, it is important to be aware of these health and design issues as they may lead to incorrect conclusions. PMID- 26260668 TI - Synthesis of Photodegradable Polystyrene with Trithiocarbonate as Linkages. AB - Multiblock polystyrenes (PS) with trithiocarbonate groups as linkages are prepared via reversible addition-fragmentation chain-transfer polymerization using polytrithiocarbonate as a chain transfer agent. The photodegradability of the multiblock PS in the solid state is investigated under UV irradiation at room temperature in an air atmosphere. The experimental results demonstrate that the trithiocarbonate linkages in the multiblock PS can be broken under UV light irradiation at room temperature and the multiblock PS is degraded into separate PS blocks. Gel permeation chromatography measurement reveals that the molecular weight of multiblock PS is reduced from 27 900 to 7900 g mol(-1) after UV light irradiation for 745 h. Moreover, the thermal stability of the multiblock PS is examined and the results indicate that the incorporation of trithiocarbonate shows little influence on the thermal stability of multiblock PS. PMID- 26260669 TI - HTLV-1-associated adult T cell leukemia is highly susceptible to Navitoclax due to enhanced Bax expression. AB - Over-expression of Bcl-2, Bcl-xL and Bcl-w is frequently associated with cancer resistance to chemotherapy. Navitoclax (ABT-263), an orally bio-available small molecule mimetic of the Bcl-2 homology domain 3, specifically inhibits Bcl-2, Bcl xL and Bcl-w. Despite promising results obtained from the clinical trials, the use of Navitoclax in patients is dose-limited due to induction of death of platelets via inhibition of Bcl-xL and subsequent thrombocytopenia. This side effect limits the use of Navitoclax in low doses and to very sensitive tumors. In this study, we show that HTLV-1-associated adult T-cell leukemia/lymphoma (ATL) cells, which over-express Bcl-2, Bcl-xL and Bcl-w, show a 10- to 20-fold higher sensitivity (EC50 = ~ 25-50 nM) to Navitoclax compared to non-HTLV-1-associated leukemic cells (EC50 = ~ 1 MUM). Investigation of the molecular mechanisms revealed that the HTLV-1 oncogenic protein Tax up-regulates expression of the pro apoptotic protein Bax which enhances the therapeutic efficacy of Navitoclax. In addition, we show that agents that inhibit the transcription elongation or translation initiation such as Wogonin and Roc-A can further decrease the effective dose of Navitoclax. Our study suggests that HTLV-1 ATL may be a good candidate disease for low dose Navitoclax therapy and probably with less risk of thrombocytopenia. PMID- 26260670 TI - Overweight Perception: Associations with Weight Control Goals, Attempts, and Practices among Chinese Female College Students. AB - BACKGROUND: Concurrent with the dramatic cultural and economic shifts occurring as mainland China becomes increasingly "Westernized," the weight perceptions, ideal body weight, and weight management goals and practices of Chinese females have also undergone significant changes. OBJECTIVE: To investigate relationships between overweight status, weight perception patterns, and weight management goals and practices in Chinese female college students. DESIGN/PARTICIPANTS/SETTING: A cross-sectional analysis was conducted with data from 902 female subjects aged 18 to 25 years participating in the China Seven Cities Study, a health promotion and smoking prevention study conducted in mainland China in 2003. MAIN OUTCOME MEASURES/STATISTICAL ANALYSES: Logistic regression models were used to explore associations between overweight status, weight perception, specific weight management goals and practices, and current levels of vigorous-intensity physical activity and food consumption. RESULTS: Based on World Health Organization standards for Asian adults, 16.7% of college females were overweight or obese, although 50.8% considered themselves to be "too heavy." Among participants perceiving themselves as overweight (n=458), 69.2% (n=371) were inaccurate and did not meet criteria for overweight or obese. The percentage of participants attempting weight loss was 48.2%, and 33.1% wanted to maintain their current weight. Attempts to lose or maintain weight were related to actual and perceived weight status, but not to increased vigorous-intensity physical activity or fruit and vegetable intake, nor to decreased consumption of sweets, soda, Western fast foods, and fried foods. Only 21.5% of participants desiring weight loss or maintenance reported using a combination of vigorous intensity physical activity and a reduced-fat and -calorie diet, whereas 20.2% tried extreme methods such as fasting, using diet pills, vomiting, or smoking. CONCLUSIONS: Our findings underscore the need to promote healthy weight management practices among Chinese female college students, with an emphasis on diet and physical activity strategies that encourage balance rather than extremes. PMID- 26260671 TI - "I Don't Want Them to Feel Different": A Mixed Methods Study of Parents' Beliefs and Dietary Management Strategies for Their Young Children with Type 1 Diabetes Mellitus. AB - BACKGROUND: Many young children with type 1 diabetes mellitus (T1DM) do not consume a healthful diet; exactly why this occurs despite T1DM education remains poorly understood. OBJECTIVE: This study describes parents' perceptions of healthful eating for T1DM in young children and identifies factors related to parents' dietary management. DESIGN: A cross-sectional, mixed-methods study was performed. Parents completed a questionnaire, 3-day weighed diet record, and a semi-structured interview regarding their perceptions of healthful eating for T1DM and their dietary management practices. PARTICIPANTS/SETTING: Twenty-three families, recruited from a pediatric diabetes clinic in the midwestern United States between February 2012 and April 2013, participated. Eligible families had a child with T1DM who was 1 to 6 years old, at least 6 months from diagnosis, and was following an intensive insulin regimen. STATISTICAL ANALYSES PERFORMED: Mean scores and percentages were calculated from the diet diaries and parent questionnaires, and parents' interviews were coded to identify common themes. RESULTS: Results showed that while parents may believe they know what constitutes a healthful diet for T1DM, they do not always feed their child a healthful diet. Parent-identified barriers to healthful eating included limited time to prepare homemade meals, perceived higher costs of healthier foods, the influence of peers on children's food preferences, and picky eating. Parents also discussed a desire not to limit their child's diet or make their child "feel different," which many parents said often led them to give into their child's requests for less healthful food options. CONCLUSIONS: Parents of young children with T1DM identified several barriers to healthful eating that are common for all parents, such as time constraints, expense, and child food preferences. However, unique themes emerged, including parents' desire not to limit their child's diet or make their child "feel different." Nutrition components of T1DM education should include psychological and behavioral strategies to help parents manage these unique concerns. PMID- 26260672 TI - Using the Hospital Nutrition Environment Scan to Evaluate Health Initiative in Hospital Cafeterias. AB - BACKGROUND: Health-promoting environments advance health and prevent chronic disease. Hospitals have been charged to promote health and wellness to patients, communities, and 5.3 million adults employed in United States health care environments. METHODS: In this cross-sectional observational study, the Hospital Nutrition Environment Scan (HNES) was used to measure the nutrition environment of hospital cafeterias and evaluate the influence of the LiVe Well Plate health initiative. Twenty-one hospitals in the Intermountain West region were surveyed between October 2013 and May 2014. Six hospitals participated in the LiVe Well Plate health initiative and were compared with 15 hospitals not participating. The LiVe Well Plate health initiative identified and promoted a healthy meal defined as <600 kcal, <700 mg sodium, and <30% fat. Signage with nutrition information and health initiative branding were also posted at point of purchase. Hospital cafeterias were scored on four subcategories: facilitators and barriers, grab-and-go items, menu offerings, and selection options at point of purchase. RESULTS: Overall, hospitals scored 35.3+/-13.7 (range=7 to 63) points of 86 total possible points. Cafeterias in health initiative hospitals had significantly higher mean nutrition composite scores compared with non-health initiative hospitals (49.2 vs 29.7; P<0.001). CONCLUSIONS: Promoting healthy entrees with nutrition information and branding has a positive influence on the nutrition environment of hospital cafeterias. Additional research is needed to quantify and strategize ways to improve nutrition environments within hospital cafeterias and assess the influence on healthy lifestyle behaviors. PMID- 26260673 TI - Enhanced Peptide Stability Against Protease Digestion Induced by Intrinsic Factor Binding of a Vitamin B12 Conjugate of Exendin-4. AB - Peptide digestion from proteases is a significant limitation in peptide therapeutic development. It has been hypothesized that the dietary pathway of vitamin B12 (B12) may be exploited in this area, but an open question is whether B12-peptide conjugates bound to the B12 gastric uptake protein intrinsic factor (IF) can provide any stability against proteases. Herein, we describe a new conjugate of B12 with the incretin peptide exendin 4 that demonstrates picomolar agonism of the glugacon-like peptide-1 receptor (GLP1-R). Stability studies reveal that Ex-4 is digested by pancreatic proteases trypsin and chymotrypsin and by the kidney endopeptidase meprin beta. Prebinding the B12 conjugate to IF, however, resulted in up to a 4-fold greater activity of the B12-Ex-4 conjugate relative to Ex-4, when the IF-B12-Ex-4 complex was exposed to 22 MUg/mL of trypsin, 2.3-fold greater activity when exposed to 1.25 MUg/mL of chymotrypsin, and there was no decrease in function at up to 5 MUg/mL of meprin beta. PMID- 26260674 TI - Nanocontact Disorder in Nanoelectronics for Modulation of Light and Gas Sensitivities. AB - To fabricate reliable nanoelectronics, whether by top-down or bottom-up processes, it is necessary to study the electrical properties of nanocontacts. The effect of nanocontact disorder on device properties has been discussed but not quantitatively studied. Here, by carefully analyzing the temperature dependence of device electrical characteristics and by inspecting them with a microscope, we investigated the Schottky contact and Mott's variable-range hopping resistances connected in parallel in the nanocontact. To interpret these parallel resistances, we proposed a model of Ti/TiOx in the interface between the metal electrodes and nanowires. The hopping resistance as well as the nanocontact disorder dominated the total device resistance for high-resistance devices, especially at low temperatures. Furthermore, we introduced nanocontact disorder to modulate the light and gas responsivities of the device; unexpectedly, it multiplied the sensitivities compared with the intrinsic sensitivity of the nanowires. Our results improve the collective understanding of electrical contacts to low-dimensional semiconductor devices and will aid performance optimization in future nanoelectronics. PMID- 26260675 TI - Secretory pattern and regulatory mechanism of growth hormone in cattle. AB - The ultradian rhythm of growth hormone (GH) secretion has been known in several animal species for years and has recently been observed in cattle. Although the physiological significance of the rhythm is not yet fully understood, it appears essential for normal growth. In this review, previous studies concerning the GH secretory pattern in cattle, including its ultradian rhythm, are introduced and the regulatory mechanism is discussed on the basis of recent findings. PMID- 26260676 TI - Informativity renders a referent more accessible: Evidence from eyetracking. AB - The amount of information attached to a noun phrase (henceforth, NP) has been shown to enhance accessibility and increase pronominal reference in language production. However, both the effect of information quantity on the comprehension of ambiguous pronouns and the time course of any informativity effect have been left unexplored. In two eyetracking experiments, we investigated how additional information on the part of NP referents influenced the resolution of following ambiguous pronouns. The results of the first experiment revealed an informativity effect, with more looks to the informationally richer referent than to the competitor. However, the effect of additional information emerged late in time when the referent was the object of the verb. The second experiment replicated the results of the first and also showed that, consistent with the online results, an ambiguous pronoun is interpreted as referring to the informationally richer NP in an offline, explicit pronoun resolution task. The results lend support to theories of language processing that assume that explicit information increases the accessibility of the associated concept, in contrast to approaches that assume that accessibility is associated with givenness. PMID- 26260677 TI - Whole-genome sequencing provides insight into the genetics of major depressive disorder. PMID- 26260678 TI - Reconstitution of Human Cytomegalovirus-Specific CD4+ T Cells is Critical for Control of Virus Reactivation in Hematopoietic Stem Cell Transplant Recipients but Does Not Prevent Organ Infection. AB - The relative contribution of human cytomegalovirus (HMCV)-specific CD4(+) and CD8(+) T cells to the control of HCMV infection in hematopoietic stem cell transplant (HSCT) recipients is still controversial. HCMV reactivation and HCMV specific CD4(+) and CD8(+) T cell reconstitution were monitored for 1 year in 63 HCMV-seropositive patients receiving HSCT. HCMV reactivation was detected in all but 2 patients. In 20 of 63 (31.7%) patients (group 1) HCMV infection resolved spontaneously, whereas 32 of 63 (50.8%) patients (group 2) controlled the infection after a single short-course of pre-emptive therapy and the remaining 9 (14.3%) patients (group 3) suffered from relapsing episodes of HCMV infection, requiring multiple courses of antiviral therapy. The kinetics and magnitude of HCMV-specific CD8(+) T cell reconstitution were comparable among the 3 groups, but HCMV-specific CD4(+) T cells were lower in number in patients requiring antiviral treatment. HCMV-seronegative donors, as well as unrelated donors (receiving antithymocyte globulin) and acute graft-versus-host disease (GVHD) were associated with both delayed HCMV-specific CD4(+) T cell reconstitution and severity of infection. Conversely, these risk factors had no impact on HCMV specific CD8(+) T cells. Eight patients with previous GVHD suffered from HCMV gastrointestinal disease, although in the presence of HCMV-specific CD4(+) and CD8(+) systemic immunity and undetectable HCMV DNA in blood. Reconstitution of systemic HCMV-specific CD4(+) T cell immunity is required for control of HCMV reactivation in adult HSCT recipients, but it may not be sufficient to prevent late-onset organ localization in patients with GVHD. HCMV-specific CD8(+) T cells contribute to control of HCMV infection, but only after HCMV-specific CD4(+) T cell reconstitution. PMID- 26260679 TI - Phase II Trial of Reduced-Intensity Busulfan/Clofarabine Conditioning with Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Acute Myeloid Leukemia, Myelodysplastic Syndromes, and Acute Lymphoid Leukemia. AB - Clofarabine has potent antileukemia activity and its inclusion in reduced intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (HSCT) for acute leukemia could potentially improve outcomes. We conducted a phase II study of busulfan (.8 mg/kg i.v. twice daily on days -5, -4, -3, and -2) with clofarabine (40 mg/m(2) i.v. daily on days -5, -4, -3, and -2) conditioning before allogeneic 8/8 HLA-matched related or unrelated HSCT. The primary endpoint was donor neutrophil engraftment by day +40. Secondary endpoints included nonrelapse mortality (NRM), acute and chronic graft-versus-host disease (GVHD), progression-free survival (PFS), and overall survival (OS). Thirty-four patients (acute myeloid leukemia [AML], n = 25; myelodysplastic syndromes, n = 5; and acute lymphoid leukemia, n = 4) were enrolled. Day 40+ engraftment with donor chimerism was achieved in 33 of 34 patients with 1 patient dying before count recovery. Day 100 and 1-year NRM were 5.9% (95% confidence interval [CI], 1.0 to 17.4) and 24% (95% CI, 11 to 39), respectively. The 2-year relapse rate was 26% (95% CI, 13 to 42). Cumulative incidences of acute and chronic GVHD were 21% and 44%, respectively. The 2-year PFS was 50% (95% CI, 32 to 65) and OS was 56% (95% CI, 38 to 71). For patients with AML in first complete remission, 2-year PFS and OS were both 82% (95% CI, 55 to 94). RIC with busulfan and clofarabine leads to successful engraftment with acceptable rates of NRM and GVHD. PMID- 26260680 TI - Role of ADAM17 in the non-cell autonomous effects of oncogene-induced senescence. AB - INTRODUCTION: Cellular senescence is a terminal cell proliferation arrest that can be triggered by oncogenes. One of the traits of oncogene-induced senescence (OIS) is the so-called senescence-associated secretory phenotype or senescence secretome. Depending on the context, the non-cell autonomous effects of OIS may vary from tumor suppression to promotion of metastasis. Despite being such a physiological and pathologically relevant effector, the mechanisms of generation of the senescence secretome are largely unknown. METHODS: We analyzed by label free proteomics the secretome of p95HER2-induced senescent cells and compared the levels of the membrane-anchored proteins with their transcript levels. Then, protein and RNA levels of ADAM17 were evaluated by using Western blot and reverse transcription-polymerase chain reaction, its localization by using biotin labeling and immunofluorescence, and its activity by using alkaline phosphatase tagged substrates. The p95HER2-expressing cell lines, senescent MCF7 and proliferating MCF10A, were analyzed to study ADAM17 regulation. Finally, we knocked down ADAM17 to determine its contribution to the senescence-associated secretome. The effect of this secretome was evaluated in migration assays in vitro and in nude mice by assessing the metastatic ability of orthotopically co injected non-senescent cells. RESULTS: Using breast cancer cells expressing p95HER2, a constitutively active fragment of the proto-oncogene HER2 that induces OIS, we show that the extracellular domains of a variety of membrane-bound proteins form part of the senescence secretome. We determine that these proteins are regulated transcriptionally and, in addition, that their shedding is limited by the protease ADAM17. The activity of the sheddase is constrained, at least in part, by the accumulation of cellular cholesterol. The blockade of ADAM17 abrogates several prometastatic effects of the p95HER2-induced senescence secretome, both in vitro and in vivo. CONCLUSIONS: Considering these findings, we conclude that ectodomain shedding is tightly regulated in oncogene-induced senescent cells by integrating transcription of the shedding substrates with limiting ADAM17 activity. The remaining activity of ADAM17 contributes to the non cell autonomous protumorigenic effects of p95HER2-induced senescent cells. Because ADAM17 is druggable, these results represent an approximation to the pharmacological regulation of the senescence secretome. PMID- 26260681 TI - [Surface ECG characteristics of right and left atrial flutter]. AB - INTRODUCTION: Atrial tachycardia in virtually all areas of both atria has become more important in the clinical management of patients with previous complex atrial fibrillation ablation. Accurate interpretation of surface electrocardiogram (ECG) characteristics is of paramount importance to localize the origin of atrial tachycardia, particularly for planning interventional treatment. This article highlights the ECG features of different types of right and left atrial tachycardia. DEFINITION: Typical right atrial flutter through the cavotricuspid isthmus conducts septally in a cranial direction and demonstrates sawtooth-like flutter waves which start negative in II, III and aVF and then show a steep slope upwards to the isoelectric line. The flutter rate typically ranges between 240-250 beats/min. In contrast, right atrial flutter in a clockwise rotation, flutter around the vena cava inferior or superior and around a scar (e.g. after cardiac surgery) show positive or biphasic flutter waves (lower or upper loop reentry). Left atrial flutter waves (e.g. around the mitral valve or around the pulmonary veins) are very heterogeneous and are typically positive in V1 as the left atrium is located in the posterior mediastinum. CONCLUSION: Specific knowledge of flutter wave morphology in surface ECG facilitates planning and performance of the ablation strategy. PMID- 26260682 TI - [The ECG of athletes]. AB - INTRODUCTION: There has been a long standing controversy on the role of a resting electrocardiogram (ECG) in the preparticipation examination of athletes, as well as in children and adolescents, in leisure time and competitive athletes. Besides other arguments, this was due to the limited validity, which led to false positive and false negative findings. METHODS: Recent studies from different research groups yielded a significant improvement in establishing ECG criteria in athletes to discriminate normal from abnormal or pathological findings in athletes. This is additionally supported and improved by a software-based ECG device considering the new Seattle criteria. These new criteria from the Seattle conference reliably discriminate normal from abnormal findings. Frequent ECG findings in athletes, especially in those engaged in endurance sports are sinus bradycardia, atrioventricular (AV) block and signs of left ventricular hypertrophy. RESULTS: Abnormal findings are related to structural left ventricular alterations due to cardiomyopathy, mainly hypertrophic with or without outflow tract obstruction, arrhythmogenic right ventricular cardiomyopathy (ARVC) and dilated cardiomyopathy. The ECG findings suggestive of electrical conductance disorders are observed in channelopathies, Wolff-Parkinson White (WPW) syndrome supraventricular arrhythmias or disturbances of cardiac conduction. The main diseases are long or short QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia. Atrial fibrillation, mostly paroxysmal, is also now more frequently observed especially in middle aged endurance athletes. CONCLUSION: Interpretation of ECG in young and older athletes requires in-depth knowledge in cardiology and sports medicine. The interpretation can only be carried out by considering medical history, clinical examination and ethnicity. Profound and long-term experience of athlete's ECG interpretation is required to protect athletes and to prevent cardiac emergencies. PMID- 26260683 TI - HA14-1 potentiates apoptosis in B-cell cancer cells sensitive to a peptide disrupting IP 3 receptor / Bcl-2 complexes. AB - Anti-apoptotic B-cell lymphoma 2 (Bcl-2) is commonly upregulated in hematological cancers, including B-cell chronic lymphocytic leukemia (B-CLL) and diffuse large B-cell lymphoma (DLBCL), thereby protecting neoplastic cells from oncogenic stress-induced apoptosis. Bcl-2 executes its anti-apoptotic function at two different sites in the cell. At the mitochondria, Bcl-2 via its hydrophobic cleft interacts with pro-apoptotic Bcl-2 family members to inhibit apoptosis. At the endoplasmic reticulum (ER), Bcl-2 via its Bcl-2 homology (BH)4 domain, prevents excessive Ca(2+) signals by interacting with the inositol 1,4,5-trisphosphate receptor (IP3R), an intracellular Ca(2+)-release channel. A peptide tool (BIRD-2) that targets the BH4 domain of Bcl-2 reverses Bcl-2's inhibitory action on IP3Rs and can trigger pro-apoptotic Ca(2+)signals in B-cell cancer cells. Here, we explored whether HA14-1, a Bcl-2 inhibitor that also inhibits sarco/endoplasmic reticulum Ca(2+)-ATPases (SERCA), could potentiate BIRD-2-induced cell death. We measured apoptosis in Annexin V/7-AAD stained cells using flow cytometry and intracellular Ca(2+) signals in Fura2-AM-loaded cells using an automated fluorescent plate reader. HA14-1 potentiated BIRD-2-induced Ca(2+) release from the ER and apoptosis in both BIRD-2-sensitive DLBCL cell lines (SU-DHL-4) and in primary B-CLL cells. BIRD-2-resistant DLBCL cells (OCI-LY-1) were already very sensitive to HA14-1. Yet, although BIRD-2 moderately increased Ca(2+) levels in HA14-1-treated cells, apoptosis was not potentiated by BIRD-2 in these cells. These results further underpin the relevance of IP3R-mediated Ca(2+) signaling as a therapeutic target in the treatment of Bcl-2-dependent B-cell malignancies and the advantage of combination regimens with HA14-1 to enhance BIRD-2-induced cell death. PMID- 26260684 TI - The significance of Hox gene collinearity. AB - Arthropods and vertebrates inherited their Hox clusters from an ancestral cluster of at least six genes already present in their last common ancestor, Urbilateria. Clustering and a common transcriptional direction are both likely features of the way that the gene complex first arose in a process of tandem gene duplication. Spatial collinearity (correspondence between ordering of Hox genes along the chromosome and their expression patterns along the head-tail axis) has been conserved in many animal groups and is likely to have been already present in Urbilateria. It is not known why the Hox cluster evolved with spatial collinearity. Four models are discussed. These vary in the significance they place upon Hox chromatin structure, and also on whether they propose that collinearity is primarily concerned with establishment or maintenance of Hox expression. Published proposals to explain spatial collinearity, which invoke enhancer sharing, chromatin closing or chromatin opening, are either problematic or can offer only partial explanations. In an alternative proposal it is suggested here that spatial collinearity evolved principally to maximise physical segregation, and thereby minimise incidence of boundaries, between active and inactive genes within the Hox cluster. This is to minimise erroneous transfer of transcriptional activity, or inactivity, between adjacent Hox genes. PMID- 26260685 TI - Expression patterns of CREB binding protein (CREBBP) and its methylated species during zebrafish development. AB - Proper embryonic development requires a fine-tuned control of gene expression, which is achieved in part through the activity of transcription coactivators or corepressors. The nuclear coactivator cAMP-response element-binding protein (CREB) binding protein (CREBBP or CBP) interacts with numerous transcription factors and thereby plays a key role in various signaling pathways. Interestingly, in cell-based studies CREBBP activity is modulated by post translational modifications such as methylation on arginine residues which is catalyzed by coactivator-associated arginine methyltransferase 1 (CARM1). However, whether and where CREBBP, and in particular its methylated forms, are expressed during development in vertebrates has not been addressed so far. Here, we analyzed the expression of the two crebbp genes (crebbpa & crebbpb) during zebrafish development using both RT-qPCR and in situ hybridization. We found that while crebbpa expression is higher in posterior, caudal nascent somites during somitogenesis, crebbpb accumulates in anterior, rostral, and more mature somites. In addition, crebbpa mRNA is enriched in the central myotome at 24 hpf indicating that its expression is spatially and temporally controlled. We next characterized the expression of CREBBP protein from blastula to gastrula stages by immunohistochemistry. We found that while CREBBP is clearly cytoplasmic in the early blastula, it becomes both cytoplasmic and nuclear at 30% epiboly before turning mainly nuclear during gastrulation. Of interest, CREBBP methylated species appear to be mainly nuclear from 30% epiboly to 6-somite stage. This suggests that methylation may regulate CREBBP import to the nucleus during zebrafish development and could therefore participate in the control of early developmental processes. PMID- 26260687 TI - Toll free but not judgment free: evaluating postabortion support services in Ontario. AB - INTRODUCTION: Crisis pregnancy centers (CPCs) account for the majority of advertised postabortion support providers in Ontario, Canada's largest and most populous province. Although the deceptive tactics used by CPCs to dissuade women from seeking abortion care are well documented, their provision of postabortion support has not been previously explored. Our study aimed to fill this gap. METHODS: In 2014-2015, we conducted a mystery client study with 17 postabortion support providing organizations in Ontario. We used a predetermined character profile and set of prompts to seek phone-based services. Each interaction began with "I'm looking to talk to someone about my abortion." The interactions developed organically and mimicked the experience of a woman seeking postabortion support. We audio recorded and transcribed all interactions and used both inductive and deductive analytic techniques in our evaluation. RESULTS: We spoke with three secular and three religiously affiliated talklines, one sexual health center and 10 CPCs offering phone-based support. Although all counselors effectively used active listening techniques such as supportive utterances and attentive silences, the interactions with lay counselors from religious talklines and CPCs contained shaming and stigmatizing language and medically inaccurate information. These interactions appear to be premised on the counselors' belief that abortion is traumatic and always requires a grieving process, regardless of the client's expressed feelings and needs. CONCLUSIONS: The expanded provision of postabortion support by CPCs in Ontario represents a new method for these organizations to pathologize abortion. Our findings suggest that their services are judgmental and shaming, thereby contributing to abortion stigma. IMPLICATIONS: Postabortion support services appear to be a new frontier by which CPCs are able to stigmatize and pathologize abortion. Increasing awareness of and access to existing nonjudgmental, nondirective postabortion services appears warranted. PMID- 26260686 TI - Improved binding site assignment by high-resolution mapping of RNA-protein interactions using iCLIP. AB - Individual-nucleotide resolution crosslinking and immunoprecipitation (iCLIP) allows the determination of crosslinking sites of RNA-binding proteins (RBPs) on RNAs. iCLIP is based on ultraviolet light crosslinking of RBPs to RNA, reverse transcription and high-throughput sequencing of fragments terminating at the site of crosslinking. As a result, start sites of iCLIP fragments are expected to cluster with a narrow distribution, typically representing the site of direct interaction between the RBP and the RNA. Here we show that for several RBPs (eIF4A3, PTB, SRSF3, SRSF4 and hnRNP L), the start sites of iCLIP fragments show a fragment length-dependent broader distribution that can be shifted to positions upstream of the known RNA-binding site. We developed an analysis tool that identifies these shifts and can improve the positioning of RBP binding sites. PMID- 26260688 TI - MicroRNA-338 inhibits migration and proliferation by targeting hypoxia-induced factor 1alpha in nasopharyngeal carcinoma. AB - Nasopharyngeal cancer (NPC) is an endemic type of head and neck cancer with a high rate of cervical lymph node metastasis. An increasing number of studies have shown that microRNAs (miRNAs) play a key role in the development and progression of NPC. miR-338-3p has been demonstrated as an anti-oncogene in different solid tumors. The aim of the present study was to investigate the potential role of miR 338-3p in the development and progression of NPC. Compared with normal samples, our data showed that miR-338-3p were downregulated in NPC tissues and cells. The luciferase assay demonstrated that HIF-1alpha was a direct target of miR-338-3p. We also found that miR-338-3p regulated the expression levels of HIF-1alpha, respectively. Overexpression of miR-338-3p in NPC cells significantly inhibited cell proliferation, and migration. Conversely, miR-338-3p knockdown in cells with lower endogenous expression levels significantly reduced antitumor behavior. Furthermore, enforced expression of miR-338-3p led to a decline in ERK phosphorylation as well as inhibited the hypoxia induced epithelial to mesenchymal transition. Cells pre-transfected with miR-338-3p can overcome hypoxia-mediated cisplatin resistance. Taken together, we found that miR-338-3p directly targeted HIF-1alpha, and we provide insight into NPC initiation and progression, possibly representing a novel therapeutic target. PMID- 26260689 TI - Marker vaccine potential of foot-and-mouth disease virus with large deletion in the non-structural proteins 3A and 3B. AB - Foot-and-mouth disease (FMD) is a highly contagious, economically important disease of transboundary importance. Regular vaccination with chemically inactivated FMD vaccine is the major means of controlling the disease in endemic countries like India. However, the traditional inactivated vaccines may sometimes contain traces of FMD viral (FMDV) non-structural protein (NSP), therefore, interfering with the NSP-based serological discrimination between infected and vaccinated animals. The availability of marker vaccine for differentiating FMD infected from vaccinated animals (DIVA) would be crucial for the control and subsequent eradication of FMD in India. In this study, we constructed a negative marker FMDV serotype O virus (vaccine strain O IND R2/1975), containing dual deletions of amino acid residues 93-143 and 10-37 in the non-structural proteins 3A and 3B, respectively through reverse genetics approach. The negative marker virus exhibited similar growth kinetics and plaque morphology in cell culture as compared to the wild type virus. In addition, we also developed and evaluated an indirect ELISA (I-ELISA) targeted to the deleted 3AB NSP region (truncated 3AB) which could be used as a companion differential diagnostic assay. The diagnostic sensitivity and specificity of the truncated 3AB I-ELISA were found to be 95.5% and 96%, respectively. The results from this study suggest that the availability negative marker virus and companion diagnostic assay could open a promising new avenue for the application of DIVA compatible marker vaccine for the control of FMD in India. PMID- 26260691 TI - Clinical differences between botulinum neurotoxin type A and B. AB - In humans, the therapeutic use of botulinum neurotoxin A (BoNT/A) is well recognized and continuously expanding. Four BoNTs are widely available for clinical practice: three are serotype A and one is serotype B: onabotulinumtoxinA (A/Ona), abobotulinumtoxinA (A/Abo) and incobotulinumtoxinA (A/Inco), rimabotulinumtoxinB (B/Rima). A/Abo, A/Inco, A/Ona and B/Rima are all licensed worldwide for cervical dystonia. In addition, the three BoNT/A products are approved for blepharospasm and focal dystonias, spasticity, hemifacial spasm, hyperhidrosis and facial lines, with remarkable regional differences. These toxin brands differ for specific activity, packaging, constituents, excipient, and storage. Comparative literature assessing the relative safety and efficacy of different BoNT products is limited, most data come from reports on small samples, and only a few studies meet criteria of evidence-based medicine. One study compared the effects of BoNT/A and BoNT/B on muscle activity of healthy volunteers, showing similar neurophysiological effects with a dose ratio of 1:100. In cervical dystonia, when comparing the effects of BoNT/A and BoNT/B, results are more variable, some studies reporting roughly similar peak effect and overall duration (at a ratio of 1:66, others reporting substantially shorter duration of BoNT/B than BoNT/A (at a ratio 1/24). Although the results of clinical studies are difficult to compare for methodological differences (dose ratio, study design, outcome measures), it is widely accepted that: BoNT/B is clinically effective using appropriate doses as BoNT/A (1:40-50), injections are generally more painful, in most of the studies on muscular conditions, efficacy is shorter, and immunogenicity higher. Since the earliest clinical trials, it has been reported that autonomic side effects are more frequent after BoNT/B injections, and this observation encouraged the use of BoNT/B for sialorrhea, hyperhidrosis and other non-motor symptoms. In these indications the efficacy of toxins A and B are comparable and dose ratio is 1:25-30. PMID- 26260690 TI - Measuring the effectiveness of gaseous virus disinfectants. AB - The efficacy of gaseous disinfection is critical for prevention and treatment of microbial contamination in biotechnological facilities. For an evaluation of gaseous disinfection efficacy, a down-scaled laboratory model was established, using currently available carrier tests and a custom-made dry fog box. A mixture of peroxyacetic acid and hydrogen peroxide (PAA/HP) was investigated as example, at concentrations between 0.4 and 2.9 mL/m(3) for up to 3 h for inactivation of a panel of lipid-enveloped and non-lipid-enveloped viruses. The influenza viruses were most sensitive to PAA/HP treatment and minute virus of mice was most resistant. Bovine viral diarrhea virus and reovirus III showed intermediate stability and similar inactivation kinetics. Use of the dry fog box circumvents dedicating an entire lab for the investigation, which renders the generation of data more cost-effective and allows for production of highly reproducible kinetic data. PMID- 26260692 TI - Structure of the BoNT/A1--receptor complex. AB - Botulinum neurotoxin A causes botulism but is also used for medical and cosmetic applications. A detailed molecular understanding of BoNT/A--host receptor interactions is therefore fundamental for improving current clinical applications and for developing new medical strategies targeting human disorders. Towards this end, we recently solved an X-ray crystal structure of BoNT/A1 in complex with its neuronal protein receptor SV2C. Based on our findings, we discuss the potential implications for BoNT/A function. PMID- 26260693 TI - Static self-directed sample dispensing into a series of reaction wells on a microfluidic card for parallel genetic detection of microbial pathogens. AB - A microfluidic card is described for simultaneous and rapid genetic detection of multiple microbial pathogens. The hydrophobic surface of native acrylic and a novel microfluidic mechanism termed "airlock" were used to dispense sample into a series of 64 reaction wells without the use of valves, external pumping peripherals, multiple layers, or vacuum assistance. This airlock mechanism was tested with dilutions of whole human blood, saliva, and urine, along with mock samples of varying viscosities and surface tensions. Samples spiked with genomic DNA (gDNA) or crude lysates from clinical bacterial isolates were tested with loop mediated isothermal amplification assays (LAMP) designed to target virulence and antibiotic resistance genes. Reactions were monitored in real time using the Gene-Z, which is a portable smartphone-driven system. Samples loaded correctly into the microfluidic card in 99.3% of instances. Amplification results confirmed no carryover of pre-dispensed primer between wells during sample loading, and no observable diffusion between adjacent wells during the 60 to 90 min isothermal reaction. Sensitivity was comparable between LAMP reactions tested within the microfluidic card and in conventional vials. Tests demonstrate that the airlock card works with various sample types, manufacturing techniques, and can potentially be used in many point-of-care diagnostics applications. PMID- 26260695 TI - Tackling inadequate vitamin D intakes within the population: fortification of dairy products with vitamin D may not be enough. AB - Dietary recommendations for vitamin D are designed by authoritative agencies to prevent vitamin D deficiency in the population, and while individual target intakes around the globe vary, they are generally between 10 and 20 MUg/day [400 800 IU/day], depending on age, assuming little or no sunshine exposure. National dietary surveys report usual intakes of vitamin D that are much lower than these targets, at about 3-7 MUg/day [120-280 IU/day], depending on usual diet, age, sex, and mandatory or voluntary fortification practices, and there is widespread dietary inadequacy around the globe. While acknowledging the valuable contribution fortified milk makes to vitamin D intakes among consumers, particularly in children, and the continued need for fortification of milk and other dairy products, additional strategic approaches to fortification, including biofortification, of a wider range of foods, have the potential to increase vitamin D intakes in the population and minimize the prevalence of low serum 25(OH)D without increasing the risk of excessive dosing. Careful consideration must be given to the range of products used for fortification and the amount of vitamin D used in each; there is a need for well-designed and sustainable fortification, and biofortification strategies for vitamin D, which use a range of foods to accommodate dietary diversity. Clinical patients may require additional consideration in terms of addressing low vitamin D status. PMID- 26260694 TI - PTHrP attenuates osteoblast cell death and apoptosis induced by a novel class of anti-cancer agents. AB - The effectiveness of chemotherapeutic agents often limits their use due to their negative effects on normal cells. Apoptosis regulatory protein (CARP)-1 functional mimetics (CFMs) belong to a novel class of compounds that possess anti cancer properties with potential utility in breast and other cancers. In this study, we investigated the growth inhibitory action of CFM-4 and -5 in bone forming osteoblasts and role of a skeletal regulator, parathyroid hormone (PTH) related peptide (PTHrP), which is frequently associated with oncologic pathologies. MC3T3E1-clone4 (MC-4) or primary osteoblasts were treated with CFMs. Western blots were performed to determine specific protein expressions. MTT, TUNEL assay, ethidium bromide/acridine orange staining, and ApoAlert caspase profiling were used to investigate cell viability and apoptosis of osteoblasts. Immunofluorescence staining was performed to observe intracellular localization of CARP-1. Our studies revealed that CFM-4 and -5 suppressed growths of mature differentiated, but not proliferating, MC-4 cells and PTHrP attenuated this effect. Mechanistically, induction of CARP-1 protein by CFM-4 and -5 was partially decreased by PTHrP. While CARP-1 increased by CFM-4 or -5 correlated with activated caspase-3, PTHrP remarkably blocked caspase-3 activation. PTHrP also influenced translocation of CFM-induced CARP-1 from the nucleus to the cytoplasm. Our data identify a new function of PTHrP in maintaining osteoblast homeostasis in chemotherapy and define a role of CARP-1 in this process. The crosstalk of PTHrP and CFM-4 and -5 signaling highlights the importance of CFMs as potential anti-cancer therapeutics in breast and other cancers which adversely affect bone. PMID- 26260696 TI - Transition from Pediatric to Adult Specialty Care for Adolescents and Young Adults with Refractory Epilepsy: A Quality Improvement Approach. AB - Adolescents and young adults with refractory epilepsy are particularly vulnerable to serious medical and psychosocial challenges during transition from pediatric to adult care. Quality improvement methods were used to address the transition process on an academic medical campus. Outcomes achieved were decreased time from referral to first appointment in the adult clinic, H=8.2, p=0.004, r=0.43; and increased social work referrals using decision support, z=10.0, p=0.0006, OR=6.13. As measured by the 13-item Patient Activation Measure, pre-post change in patient activation as an outcome of self-management education was not statistically significant. PMID- 26260697 TI - Spark anodization of titanium-zirconium alloy: surface characterization and bioactivity assessment. AB - Titanium (Ti) and its alloys have been popularly used as implant biomaterial for decades. Recently, titanium-zirconium (TiZr) alloy has been developed as an alternative implant material with improved strength in load bearing areas. Surface modification is one of the key factors to alter the surface properties to hasten osseointegration. Spark anodic oxidation (anodization) is one such method that is reported to enhance the bone formation around implants. This study aims to anodize TiZr and study its surface characteristics and cytocompatibility by cell culture experiments using osteoblast-like cells. Titanium (Ti) and TiZr discs were anodized in an electrolyte containing DL-alpha-glycerophosphate and calcium acetate (CA) at 300 V. The surface characteristics were analyzed by scanning electron microscopy, electron dispersive spectroscopy, X-ray diffraction (XRD), atomic force microscopy and goniometry. Using osteoblast-like cells viability, proliferation, differentiation and mineralization was assessed. The anodized surfaces demonstrated increased oxygen, entrapped calcium and phosphorous from the electrolyte used. XRD analysis confirmed the presence of anatase in the oxide layer. Average roughness increased and there was a significant decrease in contact angle (P < 0.01) following anodization. The anodized TiZr (aTiZr) surfaces were more nano-porous compared to anodized Ti (aTi). No significant difference was found in the viability of cells, but after 24 h the total number of cells was significantly higher (P < 0.01). Proliferation, alkaline phosphatase activity and calcium deposits were significantly higher on anodized surfaces compared to machined surfaces (P < 0.05, ANOVA). Anodization of TiZr resulted in a more nanoporous and hydrophilic surface than aTi, and osteoblast biocompatibility appeared comparable to aTi. PMID- 26260698 TI - Splenic red pulp macrophages are intrinsically superparamagnetic and contaminate magnetic cell isolates. AB - A main function of splenic red pulp macrophages is the degradation of damaged or aged erythrocytes. Here we show that these macrophages accumulate ferrimagnetic iron oxides that render them intrinsically superparamagnetic. Consequently, these cells routinely contaminate splenic cell isolates obtained with the use of MCS, a technique that has been widely used in immunological research for decades. These contaminations can profoundly alter experimental results. In mice deficient for the transcription factor SpiC, which lack red pulp macrophages, liver Kupffer cells take over the task of erythrocyte degradation and become superparamagnetic. We describe a simple additional magnetic separation step that avoids this problem and substantially improves purity of magnetic cell isolates from the spleen. PMID- 26260700 TI - The rat placental renin-angiotensin system - a gestational gene expression study. AB - BACKGROUND: The placenta is an essential organ that provides nutrients and oxygen to the developing fetus and removes toxic waste products from the fetal circulation. Maintaining placental blood osmotic pressure and blood flow is crucial for viable offspring. The renin-angiotensin system (RAS) in the placenta is a key player in the regulation of maternal-fetal blood flow during pregnancy. Therefore, the aim of this study was to determine if RAS genes are differentially expressed in mid to late gestation in rat placenta. METHODS: Whole placental tissue samples from pregnant Sprague Dawley rats at embryonic (E) days 14.25, 15.25, 17.25 and 20 (n = 6 for each gestational age) were used for genome-wide gene expression by microarray. RAS genes with expression differences of >2 fold were further analyzed. Quantitative Real-Time PCR (qPCR) was performed on independent samples to confirm and validate microarray data. Immunohistochemisty and Western blotting were performed on a differentially expressed novel RAS pathway gene (ANPEP). RESULTS: Six out of 17 genes of the RAS pathway were differentially expressed at different gestational ages. Gene expression of four genes (Angiotensin converting enzyme (Ace), angiotensin converting enzyme 2 (Ace2), membrane metalloendopeptidase (Mme) and angiotensin II receptor 1A (Agtr1a)) were significantly upregulated at E20 whereas two others (Thimet oligopeptidase 1 (Thop1) and Alanyl aminopeptidase (Anpep)) were downregulated at E20 prior to the onset of labour. These changes were confirmed by qPCR. Western blots revealed no overall differences in ANPEP protein expression in the placentae. Immunohistochemical studies, however, indicated that the localization of ANPEP differed at E17.25 and E20 as ANPEP localization in the giant trophoblast cell of the junctional zone was no longer detectable at E20. CONCLUSIONS: The current study investigated the expression of members of the RAS pathway in rat placentae and observed significantly altered expression of 6 RAS genes at 4 gestational ages. These findings present the need for further comprehensive investigation of RAS genes in normal and complicated pregnancies. PMID- 26260701 TI - Brachytherapy: state-of-the-art radiotherapy in prostate cancer. PMID- 26260702 TI - Structural Elucidation and Structure-Anti-inflammatory Activity Relationships of Cembranoids from Cultured Soft Corals Sinularia sandensis and Sinularia flexibilis. AB - New cembranoids 4-carbomethoxyl-10-epigyrosanoldie E (1), 7-acetylsinumaximol B (2), diepoxycembrene B (6), dihydromanaarenolide I (8), and isosinulaflexiolide K (9), along with 11 known related metabolites, were isolated from cultured soft corals Sinularia sandensis and Sinularia flexibilis. The structures were elucidated by means of infrared, mass spectrometry, and nuclear magnetic resonance techniques, and the absolute configurations of 1, 4, 9, and 15 were further confirmed by single-crystal X-ray diffraction analysis. The absolute configurations of these coral metabolites and comparison with known analogues showed that one hypothesis (that cembrane diterpenes possessing an absolute configuration of an isopropyl group at C1 obtained from Alcyonacean soft corals belong to the alpha series, whereas analogues isolated from Gorgonacean corals belong to the beta series) is not applicable for a small number of cembranoids. An in vitro anti-inflammatory study using LPS-stimulated macrophage-like cell line RAW 264.7 revealed that compounds 9-14 significantly suppressed the accumulation of pro-inflammatory proteins, iNOS and COX-2. Structure-activity relationship analysis indicated that cembrane-type compounds with one seven membered lactone moiety at C-1 are potential anti-inflammatory agents. This is the first culture system in the world that has successfully been used to farm S. sandensis. PMID- 26260703 TI - RGD-functionalized ultrasmall iron oxide nanoparticles for targeted T1-weighted MR imaging of gliomas. AB - We report a convenient approach to prepare ultrasmall Fe3O4 nanoparticles (NPs) functionalized with an arginylglycylaspartic acid (RGD) peptide for in vitro and in vivo magnetic resonance (MR) imaging of gliomas. In our work, stable sodium citrate-stabilized Fe3O4 NPs were prepared by a solvothermal route. Then, the carboxylated Fe3O4 NPs stabilized with sodium citrate were conjugated with polyethylene glycol (PEG)-linked RGD. The formed ultrasmall RGD-functionalized nanoprobe (Fe3O4-PEG-RGD) was fully characterized using different techniques. We show that these Fe3O4-PEG-RGD particles with a size of 2.7 nm are water dispersible, stable, cytocompatible and hemocompatible in a given concentration range, and display targeting specificity to glioma cells overexpressing alphavbeta3 integrin in vitro. With the relatively high r1 relaxivity (r1 = 1.4 mM(-1) s(-1)), the Fe3O4-PEG-RGD particles can be used as an efficient nanoprobe for targeted T1-weighted positive MR imaging of glioma cells in vitro and the xenografted tumor model in vivo via an active RGD-mediated targeting pathway. The developed RGD-functionalized Fe3O4 NPs may hold great promise to be used as a nanoprobe for targeted T1-weighted MR imaging of different alphavbeta3 integrin overexpressing cancer cells or biological systems. PMID- 26260704 TI - Expression of protein kinase C isoforms in cultured human Tenon's capsule fibroblast cells. AB - Members of the protein kinase C (PKC) family are involved in physiological and pathophysiological processes, and exert an important role in signal transduction. The aim of the present study was to determine which of the 12 protein kinase C (PKC) isoforms (PKCalpha, PKCbetaI, PKCbetaII, PKCgamma, PKCdelta, PKCepsilon, PKCeta, PKCtheta, PKCu, PKCzeta, PKClambda and PKCiota) were expressed in vitro in cultured human Tenon's capsule fibroblasts (HTFs). HTFs from cell passages three to five were investigated for the presence of the 12 PKC isoforms at the cellular, mRNA and protein levels using laser scanning confocal microscopy (LSCM), reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis, respectively. These analyses yielded similar results for several of the PKC isoforms (PKCalpha, PKCdelta, PKCepsilon, PKCeta, PKCu, PKCzeta, PKClambda and PKCiota); however, PKCbetaI, PKCbetaII, PKCgamma and PKCtheta were not expressed in the cultured HTFs. LSCM revealed that eight PKC isoforms, PKCalpha, PKCdelta, PKCepsilon, PKCeta, PKCu, PKCzeta, PKClambda and PKCiota, appeared almost exclusively in the cytoplasm of the cells. Notably, PKCdelta was expressed particularly well in the cytoskeleton. The present study revealed that all 12 PKC isoforms were expressed and that eight of the isoforms were present in cultured HTFs. These results will be of value when determining specific roles for the PKC isoforms in HTF proliferation, which may provide a novel therapeutic target for bleb scarring in glaucoma filtering surgery. PMID- 26260705 TI - Randomized, dose-finding trial of ghrelin treatment for chronic respiratory failure. AB - OBJECTIVES: Ghrelin, a growth hormone-releasing peptide, has shown efficacy in chronic obstructive pulmonary disease (COPD) patients in previous trials. This study was designed to evaluate the effective dose of ghrelin in chronic respiratory failure patients. METHODS: In this randomized, double-blind, dose finding, single-center study, 18 patients, including 16 with COPD, were randomly assigned to receive pulmonary rehabilitation (PR) with intravenous ghrelin at 1 MUg/kg or 2 MUg/kg, twice daily for 3 weeks. The primary outcome was the change in peak oxygen uptake ( Vo2). Secondary outcomes included changes in plasma vascular endothelial growth factor (VEGF)-A levels, and exertional cardio respiratory functions with blood gas analysis. RESULTS: With incremental exercise, there was no significant differences in the mean difference (high-dose ghrelin minus low-dose ghrelin) of peak Vo2 (1.0 mL/kg/min, 95% CI: -0.6 to 2.6 mL/kg/min, between-group, P = 0.193). However, there were significant differences in the mean difference of (i) O2 -pulse (0.6 mL/beats, 95% CI: 0.0 to 1.1 mL/beats, between-group, P = 0.035) at iso-time; and ii) PaO2 (4.2 mmHg, 95% CI: 0.2 to 8.2 mmHg, between-group, P = 0.041) and PaCO2 (-3.1 mmHg, 95% CI: -6.0 to 0.3 mmHg, between-group, P = 0.034) at peak exercise. The mean difference in the plasma VEGF-A level was significantly inhibited by high dose-ghrelin with PR ( 125.4 pg/mL, 95% CI: -235.2 to -15.5 pg/mL, between-group, P = 0.028). CONCLUSION: Although the primary outcome of the study was not met, high-dose ghrelin with PR improved exertional cardiac function and blood gas values, and inhibited circulating VEGF-A levels. PMID- 26260706 TI - Intranasal vaccination of recombinant H5N1 HA1 proteins fused with foldon and Fc induces strong mucosal immune responses with neutralizing activity: Implication for developing novel mucosal influenza vaccines. AB - The highly pathogenic avian influenza (HPAI) H5N1 virus remains a threat to public health because of its continued spread in poultry in some countries and its ability to infect humans with high mortality rate, calling for the development of effective and safe vaccines against H5N1 infection. Here, we constructed 4 candidate vaccines by fusing H5N1 hemagglutinin 1 (HA1) with foldon (HA1-Fd), human IgG Fc (HA1-Fc), foldon and Fc (HA1-FdFc) or His-tag (HA1-His). We then compared their ability to induce mucosal immune responses and neutralizing antibodies in the presence or absence of Poly(I:C) and CpG adjuvants via the intranasal route. Without an adjuvant, HA1-FdFc could elicit appreciable humoral immune responses and local mucosal IgA antibodies in immunized mice, while other vaccine candidates only induced background immune responses. In the presence of Poly(I:C) and CpG, both HA1-Fd and HA1-Fc elicited much higher levels of serum IgG and local mucosal IgA antibodies than HA1-His. Poly(I:C) and CpG could also augment the neutralizing antibody responses induced by these 4 vaccine candidates in the order of HA1-FdFc > HA1-Fc > HA1-Fd > HA1-His. These results suggest that both Fd and Fc potentiate the immunogenicity of the recombinant HA1 protein and that Poly(I:C) and CpG serve as efficient mucosal adjuvants in promoting efficacy of these vaccine candidates to induce strong systemic and local antibody responses and potent neutralizing antibodies, providing a useful strategy to develop effective and safe mucosal H5N1 vaccines. PMID- 26260707 TI - Identification of a novel homozygous SPG7 mutation by whole exome sequencing in a Greek family with a complicated form of hereditary spastic paraplegia. AB - We report the clinical description and genetic analyses of a Greek family with four individuals affected with a complicated form of hereditary spastic paraplegia (HSP) and a recessive pattern of inheritance. Exome sequencing of all affected individuals led to the identification of a homozygous 25 bp deletion predicted to lead to a frameshift and premature stop codon in the SPG7 gene, encoding paraplegin. This deletion, which is located in the first exon of the SPG7 gene, has not been previously reported and likely lead to the complete absence of the SPG7 protein. Interestingly, this family shows significant phenotypic heterogeneity further highlighting the clinical variability associated with SPG7 mutations. Our findings emphasize the clinical utility of whole exome sequencing for the molecular diagnosis of HSPs. PMID- 26260708 TI - Response to the Letter by Ozturk and Colleagues Entitled: "Inter-Arm Blood Pressure Differences May Be Important in Predicting Mortality". PMID- 26260709 TI - The effects of the Green House nursing home model on ADL function trajectory: A retrospective longitudinal study. AB - BACKGROUND: Growing attention in the past few decades has focused on improving care quality and quality of life for nursing home residents. Many traditional nursing homes have attempted to transform themselves to become more homelike emphasizing individualized care. This trend is referred to as nursing home culture change in the U.S. A promising culture change nursing home model, the Green House nursing home model, has shown positive psychological outcomes. However, little is known about whether the Green House nursing home model has positive effects on physical function compared to traditional nursing homes. OBJECTIVES: To examine the longitudinal effects of the Green House nursing home model by comparing change patterns of activities of daily living function over time between Green House home residents and traditional nursing home residents. DESIGN: A retrospective longitudinal study. SETTINGS: Four Green House organizations (nine Green House units and four traditional units). PARTICIPANTS: A total of 242 residents (93 Green House residents and 149 traditional home residents) who had stayed in the nursing home at least 6 months from admission. METHODS: The outcome was activities of daily living function, and the main independent variable was the facility type in which the resident stayed: a Green House or traditional unit. Age, gender, comorbidity score, cognitive function, and depressive symptoms at baseline were controlled. All of these measures were from a minimum dataset. Growth curve modeling and growth mixture modeling were employed in this study for longitudinal analyses. RESULTS: The mean activities of daily living function showed deterioration over time, and the rates of deterioration between Green House and traditional home residents were not different over time. Four different activities of daily living function trajectories were identified for 18 months, but there was no statistical difference in the likelihood of being in one of the four trajectory classes between the two groups. CONCLUSIONS: Although Green House nursing homes are considered to represent an innovative model changing the nursing home environment into more person-centered, this study did not demonstrate significant differences in activities of daily living function changes for residents in the Green House nursing homes compared to traditional nursing homes. Given that the Green House model continues to evolve as it is being implemented and variations within and across Green House homes are identified, large-scale longitudinal studies are needed to provide further relevant information on the effects of the Green House model. PMID- 26260711 TI - Cardiovascular medication use and cardiovascular disease in children and adolescents with type 1 diabetes: a population-based cohort study. AB - OBJECTIVES: To investigate the 5-yr prevalence and incidence rates of cardiovascular medication and cardiovascular disease before and after onset of type 1 diabetes (T1D) in children and adolescents. METHODS: Children and adolescents (<19 yr) with T1D (n = 925), defined as those who received at least two insulin prescriptions, and a four times larger reference cohort (n = 3591) with the same age and gender in the Dutch PHARMO Record Linkage System (RLS) were studied in a retrospective cohort study between 1999 and 2009. The date of first insulin dispensing was selected as the index date. RESULTS: The overall prevalence rate of cardiovascular medication use was substantially higher in the T1D cohort before (2.2 vs. 1.0%, p < 0.001) and after (9.2 vs. 3.2%, p < 0.001) the index date. After the index date angiotensin-converting enzyme inhibitors (2.0%) and statins (1.5%) were the most prevalent cardiovascular medications in the T1D cohort. The highest incidence rate of cardiovascular medication use was observed in the first year after the index date [28.1 per 1000 person years (PY)]. Furthermore, three type 1 diabetic patients were hospitalized due to cardiomyopathy (n = 2) and heart failure (n = 1) and one child from the reference group was hospitalized due to cardiomyopathy in the 5 yr after the index date. CONCLUSIONS: Children with T1D were more likely to use cardiovascular medications in the years before and after the onset of diabetes. Our study emphasizes the importance of routine screening tests and timely treatment of CVD risk factors in the pediatric population with diabetes. PMID- 26260712 TI - Costs of Venous Thromboembolism, Catheter-Associated Urinary Tract Infection, and Pressure Ulcer. AB - OBJECTIVE: To estimate differences in the length of stay (LOS) and costs for comparable pediatric patients with and without venous thromboembolism (VTE), catheter-associated urinary tract infection (CAUTI), and pressure ulcer (PU). METHODS: We identified at-risk children 1 to 17 years old with inpatient discharges in the Nationwide Inpatient Sample. We used a high dimensional propensity score matching method to adjust for case-mix at the patient level then estimated differences in the LOS and costs for comparable pediatric patients with and without VTE, CAUTI, and PU. RESULTS: Incidence rates were 32 (VTE), 130 (CAUTI), and 3 (PU) per 10 000 at-risk patient discharges. Patients with VTE had an increased 8.1 inpatient days (95% confidence interval [CI]: 3.9 to 12.3) and excess average costs of $27 686 (95% CI: $11 137 to $44 235) compared with matched controls. Patients with CAUTI had an increased 2.4 inpatient days (95% CI: 1.2 to 3.6) and excess average costs of $7200 (95% CI: $2224 to $12 176). No statistical differences were found between patients with and without PU. CONCLUSIONS: The significantly extended LOS highlights the substantial morbidity associated with these potentially preventable events. Hospitals seeking to develop programs targeting VTE and CAUTI should consider the improved turnover of beds made available by each event prevented. PMID- 26260713 TI - Global Health Education in US Pediatric Residency Programs. AB - BACKGROUND AND OBJECTIVE: Despite the growing importance of global health (GH) training for pediatric residents, few mechanisms have cataloged GH educational opportunities offered by US pediatric residency programs. We sought to characterize GH education opportunities across pediatric residency programs and identify program characteristics associated with key GH education elements. METHODS: Data on program and GH training characteristics were sought from program directors or their delegates of all US pediatric residency programs during 2013 to 2014. These data were used to compare programs with and without a GH track as well as across small, medium, and large programs. Program characteristics associated with the presence of key educational elements were identified by using bivariate logistic regression. RESULTS: Data were collected from 198 of 199 active US pediatric residency programs (99.5%). Seven percent of pediatric trainees went abroad during 2013 to 2014. Forty-nine programs (24.7%) reported having a GH track, 66.1% had a faculty lead, 58.1% offered international field experiences, and 48.5% offered domestic field experiences. Forty-two percent of programs reported international partnerships across 153 countries. Larger programs, those with lead faculty, GH tracks, or partnerships had significantly increased odds of having each GH educational element, including pretravel preparation. CONCLUSIONS: The number of pediatric residency programs offering GH training opportunities continues to rise. However, smaller programs and those without tracks, lead faculty, or formal partnerships lag behind with organized GH curricula. As GH becomes an integral component of pediatric training, a heightened commitment is needed to ensure consistency of training experiences that encompass best practices in all programs. PMID- 26260714 TI - Preterm Cognitive Function Into Adulthood. AB - BACKGROUND: Very preterm (VP; gestational age <32 weeks) and very low birth weight (VLBW; <1500 g) births are related to impaired cognitive function across the life span. It is not known how stable cognitive functions are from childhood to adulthood for VP/VLBW compared with term-born individuals and how early adult cognitive function can be predicted. METHODS: The Bavarian Longitudinal Study is a prospective geographically defined cohort study that followed 260 VP/VLBW and 229 term-born individuals from birth to adulthood. Data on cognitive function were assessed with developmental and IQ tests at 5 and 20 months and at 4, 6, 8, and 26 years of age. RESULTS: Across all assessments, VP/VLBW individuals had significantly lower IQ scores than term-born controls, even when individuals with severe cognitive impairment (n = 69) were excluded. IQ scores were found to be more stable over time for VP/VLBW than term-born individuals, yet differences in stability disappeared when individuals with cognitive impairment were excluded. Adult IQ could be predicted with fair certainty (r > 0.50) from age 20 months onward for the whole VP/VLBW sample (n = 260) and from 6 years onward for term born individuals (n = 229). CONCLUSIONS: VP/VLBW individuals more often suffer from cognitive problems across childhood into adulthood and these problems are relatively stable from early childhood onward. VP/VLBW children's risk for cognitive problems can be reliably diagnosed at the age of 20 months. These findings provide strong support for the timing of cognitive follow-up at age 2 years to plan special support services for children with cognitive problems. PMID- 26260715 TI - Presumed Arterial Gas Embolism After Breath-Hold Diving in Shallow Water. AB - Dive-related injuries are relatively common, but almost exclusively occur in recreational or scuba diving. We report 2 children with acute central nervous system complications after breath-hold diving. A 12-year-old boy presented with unilateral leg weakness and paresthesia after diving beneath the water surface for a distance of ~25 m. After ascent, he suddenly felt extreme thoracic pain that resolved spontaneously. Neurologic examination revealed right leg weakness and sensory deficits with a sensory level at T5. Spinal MRI revealed a nonenhancing T2-hyperintense lesion in the central cord at the level of T1/T2 suggesting a spinal cord edema. A few weeks later, a 13-year-old girl was admitted with acute dizziness, personality changes, confusion, and headache. Thirty minutes before, she had practiced diving beneath the water surface for a distance of ~25 m. After stepping out, she felt sudden severe thoracic pain and lost consciousness. Shortly later she reported headache and vertigo, and numbness of the complete left side of her body. Neurologic examination revealed reduced sensibility to all modalities, a positive Romberg test, and vertigo. Cerebral MRI revealed no pathologic findings. Both children experienced a strikingly similar clinical course. The chronology of events strongly suggests that both patients were suffering from arterial gas embolism. This condition has been reported for the first time to occur in children after breath-hold diving beneath the water surface without glossopharyngeal insufflation. PMID- 26260717 TI - Remission From Behavioral Dysregulation in a Child With PTSD After Receiving Procedural Ketamine. AB - Ketamine, an N-methyl-D-aspartate-type glutamate receptor antagonist, has long been used for anesthesia and has recently been investigated for its rapid antidepressant effects in adults with treatment-resistant depression and posttraumatic stress disorder (PTSD). We report a case of a child with PTSD and episodes of severe aggression and emotional dysregulation that were refractory to multiple medical and behavioral interventions. This child demonstrated sustained (8-13 days) remission from these symptoms when exposed to ketamine in the context of 2 procedures. We review the sparse literature on the uses of ketamine for behavioral purposes in children. This case suggests that ketamine should be further explored as a potential treatment option for children with severe refractory behavioral aggression. PMID- 26260716 TI - Home Reading Environment and Brain Activation in Preschool Children Listening to Stories. AB - BACKGROUND AND OBJECTIVES: Parent-child reading is widely advocated to promote cognitive development, including in recommendations from the American Academy of Pediatrics to begin this practice at birth. Although parent-child reading has been shown in behavioral studies to improve oral language and print concepts, quantifiable effects on the brain have not been previously studied. Our study used blood oxygen level-dependent functional magnetic resonance imaging to examine the relationship between home reading environment and brain activity during a story listening task in a sample of preschool-age children. We hypothesized that while listening to stories, children with greater home reading exposure would exhibit higher activation of left-sided brain regions involved with semantic processing (extraction of meaning). METHODS: Nineteen 3- to 5-year old children were selected from a longitudinal study of normal brain development. All completed blood oxygen level-dependent functional magnetic resonance imaging using an age-appropriate story listening task, where narrative alternated with tones. We performed a series of whole-brain regression analyses applying composite, subscale, and individual reading-related items from the validated StimQ-P measure of home cognitive environment as explanatory variables for neural activation. RESULTS: Higher reading exposure (StimQ-P Reading subscale score) was positively correlated (P < .05, corrected) with neural activation in the left sided parietal-temporal-occipital association cortex, a "hub" region supporting semantic language processing, controlling for household income. CONCLUSIONS: In preschool children listening to stories, greater home reading exposure is positively associated with activation of brain areas supporting mental imagery and narrative comprehension, controlling for household income. These neural biomarkers may help inform eco-bio-developmental models of emergent literacy. PMID- 26260710 TI - Blood cells: an historical account of the roles of purinergic signalling. AB - The involvement of purinergic signalling in the physiology of erythrocytes, platelets and leukocytes was recognised early. The release of ATP and the expression of purinoceptors and ectonucleotidases on erythrocytes in health and disease are reviewed. The release of ATP and ADP from platelets and the expression and roles of P1, P2Y(1), P2Y(12) and P2X1 receptors on platelets are described. P2Y(1) and P2X(1) receptors mediate changes in platelet shape, while P2Y(12) receptors mediate platelet aggregation. The changes in the role of purinergic signalling in a variety of disease conditions are considered. The successful use of P2Y(12) receptor antagonists, such as clopidogrel and ticagrelor, for the treatment of thrombosis, myocardial infarction and stroke is discussed. PMID- 26260718 TI - The Impact of Rudeness on Medical Team Performance: A Randomized Trial. AB - BACKGROUND AND OBJECTIVES: Iatrogenesis often results from performance deficiencies among medical team members. Team-targeted rudeness may underlie such performance deficiencies, with individuals exposed to rude behavior being less helpful and cooperative. Our objective was to explore the impact of rudeness on the performance of medical teams. METHODS: Twenty-four NICU teams participated in a training simulation involving a preterm infant whose condition acutely deteriorated due to necrotizing enterocolitis. Participants were informed that a foreign expert on team reflexivity in medicine would observe them. Teams were randomly assigned to either exposure to rudeness (in which the expert's comments included mildly rude statements completely unrelated to the teams' performance) or control (neutral comments). The videotaped simulation sessions were evaluated by 3 independent judges (blinded to team exposure) who used structured questionnaires to assess team performance, information-sharing, and help-seeking. RESULTS: The composite diagnostic and procedural performance scores were lower for members of teams exposed to rudeness than to members of the control teams (2.6 vs 3.2 [P = .005] and 2.8 vs 3.3 [P = .008], respectively). Rudeness alone explained nearly 12% of the variance in diagnostic and procedural performance. A model specifying information-sharing and help-seeking as mediators linking rudeness to team performance explained an even greater portion of the variance in diagnostic and procedural performance (R(2) = 52.3 and 42.7, respectively). CONCLUSIONS: Rudeness had adverse consequences on the diagnostic and procedural performance of the NICU team members. Information-sharing mediated the adverse effect of rudeness on diagnostic performance, and help-seeking mediated the effect of rudeness on procedural performance. PMID- 26260720 TI - The Way Forward for Global Health Training Programs. PMID- 26260719 TI - Inappropriate Use of Ultrasound in Management of Pediatric Cryptorchidism. AB - BACKGROUND AND OBJECTIVES: There is a limited role for ultrasound in the management of an undescended testicle (UDT). We hypothesized that ultrasound remains overused by referring physicians. Our goal was to characterize the trends, patterns, and impact of ultrasound use for UDT and to reaffirm its limited diagnostic value for this indication. METHODS: The records of boys aged 0 to 18 years with UDT in Ontario, Canada, between 2000 and 2011 were reviewed by using health administrative data housed at the Institute for Clinical and Evaluative Sciences (ICES). A second review of boys referred to our institution with UDT between 2007 and 2011 was conducted to complement the health administrative data. Trends in frequency, distribution, and costs of ultrasound use were assessed. Time delays between diagnosis and definitive management were compared between the ultrasound and non-ultrasound groups. Using our institutional data, we analyzed demographic patterns of ultrasound use and compared its diagnostic accuracy by using surgical findings as the gold standard. RESULTS: Ultrasound was used in 33.5% of provincial referrals and 50% of institutional referrals. Children who underwent ultrasound experienced an approximate 3-month delay in definitive surgical management. Ultrasound correctly predicted physical examination findings in only 54% of patients. Physicians in community practice, and those with fewer years in practice, were more likely to order ultrasound. CONCLUSIONS: Ultrasound has limited value for the management of UDT but remains widely overused, with an increasing trend over time. This practice has negative implications for access to care and cost-containment. Widespread educational efforts should be undertaken, targeting current and future referring physicians. PMID- 26260721 TI - Exercise and Vascular Function in Child Obesity: A Meta-Analysis. AB - CONTEXT: Conduit artery flow-mediated dilation (FMD) is a noninvasive index of preclinical atherosclerosis in humans. Exercise interventions can improve FMD in both healthy and clinical populations. OBJECTIVE: This systematic review and meta analysis aimed to summarize the effect of exercise training on FMD in overweight and obese children and adolescents as well as investigate the role of cardiorespiratory fitness (peak oxygen consumption [Vo2peak]) on effects observed. DATA SOURCES: PubMed, Medline, Embase, and Cinahl databases were searched from the earliest available date to February 2015. STUDY SELECTION: Studies of children and/or adolescents who were overweight or obese were included. DATA EXTRACTION: Standardized data extraction forms were used for patient and intervention characteristics, control/comparator groups, and key outcomes. Procedural quality of the studies was assessed using a modified version of the Physiotherapy Evidence Base Database scale. RESULTS: A meta-analysis involving 219 participants compared the mean difference of pre- versus postintervention vascular function (FMD) and Vo2peak between an exercise training intervention and a control condition. There was a significantly greater improvement in FMD (mean difference 1.54%, P < .05) and Vo2peak (mean difference 3.64 mL/kg/min, P < .05) after exercise training compared with controls. LIMITATIONS: Given the diversity of exercise prescriptions, participant characteristics, and FMD measurement protocols, varying FMD effect size was noted between trials. CONCLUSIONS: Exercise training improves vascular function in overweight and obese children, as indicated by enhanced FMD. Further research is required to establish the optimum exercise program for maintenance of healthy vascular function in this at-risk pediatric population. PMID- 26260722 TI - Impact of Physician Scorecards on Emergency Department Resource Use, Quality, and Efficiency. AB - BACKGROUND AND OBJECTIVES: Variability in practice patterns and resource use in the emergency department (ED) can affect costs without affecting outcomes. ED quality measures have not included resource use in relation to ED outcomes and efficiency. Our objectives were to develop a tool for comprehensive physician feedback on practice patterns relative to peers and to study its impact on resource use, quality, and efficiency. METHODS: We evaluated condition-specific resource use (laboratory tests; imaging; antibiotics, intravenous fluids, and ondansetron; admission) by physicians at 2 tertiary pediatric EDs for 4 common conditions (fever, head injury, respiratory illness, gastroenteritis). Resources used, ED length of stay (efficiency measure), and 72-hour return to ED (return rate [RR]) (balancing measure) were reported on scorecards with boxplots showing physicians their practice relative to peers. Quarterly scorecards were distributed for baseline (preintervention, July 2009-August 2010) and postintervention (September 2010-December 2011). Preintervention, postintervention, and trend analyses were performed. RESULTS: In 51 450 patient visits (24 834 preintervention, 26 616 postintervention) seen by 96 physicians, we observed reduced postintervention use of abdominal and pelvic and head computed tomography scans, chest radiographs, intravenous antibiotics, and ondansetron (P < .01 for all). Hospital admissions decreased from 7.4% to 6.7% (P = .002), length of stay from 112 to 108 minutes (P < .001), and RR from 2.2% to 2.0%. Trends for use of laboratory tests and intravenous antibiotics showed significant reduction (P < .001 and P < .05, respectively); admission trends increased, and trends for use of computed tomography scans and plain abdominal radiographs showed no change. CONCLUSIONS: Physician feedback on practice patterns relative to peers results in reduction in resource use for several common ED conditions without adversely affecting ED efficiency or quality of care. PMID- 26260723 TI - Late Preterm Infants and Neurodevelopmental Outcomes at Kindergarten. AB - BACKGROUND AND OBJECTIVE: Late preterm infants (LPIs) (gestation 34 weeks and 0 days to 36 weeks and 6 days) compared with full-term infants (FTIs) are at increased risk for mortality and short- and long-term morbidity. The objective of this study was to assess the neurodevelopmental outcomes in a longitudinal cohort study of LPIs from infancy to school age and determine predictive values of earlier developmental testing compared with school-age testing. METHODS: We used general estimating equations to calculate the odds of school readiness in a nationally representative cohort of 4900 full-term and 950 late preterm infants. We generated positive and negative predictive values of the ability of the 24 month Mental Developmental Index (MDI) scores of the Bayley Short Form, Research Edition, to predict Total School Readiness Score (TSRS) at kindergarten age. RESULTS: In multivariable analysis, late preterm infants had higher odds of worse TSRSs (adjusted odds ratio 1.52 [95% confidence interval 1.06-2.18], P = .0215). The positive predictive value of a child having an MDI of <70 at 24 months and a TSRS <5% at kindergarten was 10.4%. The negative predictive value of having an MDI of >70 at 24 months and a TSRS >5% was 96.8%. Most infants improved score ranking over the study interval. CONCLUSIONS: LPIs continue to be delayed at kindergarten compared with FTIs. The predictive validity of having a TSRS in the bottom 5% given a MDI <70 at 24 months was poor. A child who tested within the normal range (>85) at 24 months had an excellent chance of testing in the normal range at kindergarten. PMID- 26260724 TI - Hot topic: Recessive mutations in the a3(VI) collagen gene COL6A3 cause early onset isolated dystonia. PMID- 26260725 TI - Melanoma arising in a nevus of Ito: novel genetic mutations and a review of the literature on cutaneous malignant transformation of dermal melanocytosis. AB - Dermal melanocytosis refers to a spectrum of benign melanocytic proliferations that includes Mongolian spot, nevus of Ota and nevus of Ito. These lesions most commonly occur in persons of Asian or African descent and are often present at birth or develop during childhood. Very rarely, dermal melanocytoses undergo malignant transformation. There have been only 13 reports in the literature of primary cutaneous melanoma arising in dermal melanocytoses. We report a case of a Chinese woman with melanoma arising in a congenital nevus of Ito. We performed targeted next-generation sequencing of the tumor which revealed mutations of GNAQ and BAP1, suggesting that alterations in these two genes led to malignant transformation of the nevus of Ito. We also provide a summary of reports in the literature regarding primary cutaneous melanoma arising in the context of dermal melanocytosis. PMID- 26260726 TI - The effect of melatonin on sleep and quality of life in patients with advanced breast cancer. AB - BACKGROUND: Fatigue and sleep problems are prevalent in cancer patients and can be associated with disruption of circadian rhythmicity. In this prospective phase II trial, we sought to assess the effect of melatonin on circadian biomarkers, sleep, and quality of life in breast cancer patients. METHODS: Thirty-two patients with metastatic breast cancer, receiving hormonal or trastuzumab therapy, took 5 mg of melatonin at bedtime for 2 months. Before starting and after 2 months on melatonin therapy, sleep and circadian rhythmicity were assessed by actigraphy, diurnal patterns of serum cortisol, and the expression of the core clock genes PER2 and BMAL1 in peripheral blood mononuclear cells. The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire was completed for subjective parameters. RESULTS: Bedtime melatonin was associated with a significant improvement in a marker of objective sleep quality, sleep fragmentation and quantity, subjective sleep, fatigue severity, global quality of life, and social and cognitive functioning scales. Morning clock gene expression was increased following bedtime melatonin intake. Melatonin did not affect actigraphy measure of circadian rhythmicity, or the diurnal cortisol pattern. CONCLUSION: These results invite further investigation of melatonin as a potentially useful therapeutic agent for improving sleep and quality of life in cancer patients. PMID- 26260727 TI - Leveraging iPads to introduce meditation and reduce distress among cancer patients undergoing chemotherapy: a promising approach. AB - PURPOSE: Distress is common among cancer patients. Regular meditation practice has the potential to mitigate this distress and improve quality of life for this population. Introducing meditation to cancer patients can be particularly challenging given the demands on patients' time from treatment and normal life events. This internal process improvement study examined the potential benefit of utilizing iPads during chemotherapy sessions to introduce meditation and reduce distress. METHODS: Patients undergoing chemotherapy infusion were offered iPads with various meditation videos and audio files during the session. Levels of distress were measured using the distress thermometer at the beginning of chemotherapy and at the conclusion of chemotherapy. RESULTS: Seventy-three patients accepted the meditation iPads during the chemotherapy session. Among those who accepted the iPads, average distress dropped 46% by the end of the session (p < 0.0001). CONCLUSIONS: The use of iPads during chemotherapy is a potentially effective way to introduce meditation as a stress management tool for people with cancer. PMID- 26260728 TI - It's all in the timing: the importance of concurrency and short gap length in the control of genital Chlamydia trachomatis infections. PMID- 26260729 TI - Endocarditis due to gram-negative bacilli at a French teaching hospital over a 6 year period: clinical characteristics and outcome. AB - BACKGROUND: Infective endocarditis (IE) due to gram-negative bacilli (GNB) is rare. However, several studies described a change in the epidemiological profile of patients within the past few years. METHODS: We reviewed all cases diagnosed and followed in the infectious diseases ward of a French teaching hospital in Paris between 2009 and 2014, inclusive. RESULTS: Among the 17 patients with definite GNB-IE (11 male, mean age 54 years), 12 (70%) were due to non-HACEK GNB and 5 (30%) to HACEK group GNB. A prosthetic valve was involved in 10 cases (8 in non-HACEK and 2 in HACEK group). Escherichia coli (4/12 patients) and Pseudomonas aeruginosa (3/12 patients) were the most common pathogens in the first group; all the pathogens in the second group were Haemophilus spp. One-third of the patients with non-HACEK GNB had nosocomial IE, whereas injection drug use-related infections were rare (2/12). All patients with HACEK infection had at least one complication (intracardiac abscess, stroke or other systemic embolization). All patients were treated by antibiotic combination therapy during a median time of 42 days (interquartile range (IQR) = 42-42) and 10 (59%) underwent cardiac surgery. One death at 9 months was observed in the non-HACEK group. CONCLUSIONS: Regarding HACEK IE, this report supports the frequent association with vascular complications. Regarding non-HACEK GNB IE, this report supports the increasing proportion of nosocomial infections. We reported a high proportion of surgery in the therapeutic management of both HACEK and non-HACEK groups associated with no in-hospital mortality. PMID- 26260730 TI - Sterically geared tris-thioureas; transmembrane chloride transporters with unusual activity and accessibility. AB - Tris-N-arylthioureas derived in one step from 1,3,5-tris(aminomethyl)-2,4,6 triethylbenzene are remarkably effective anion carriers. With optimised aryl substituents their activities come close to the best currently known, suggesting that they might find use as readily available standards in anion transport research. PMID- 26260731 TI - Management of patient with acrometageria for routine dental treatment: A case report. AB - The population of special needs patients in dental offices is growing. Therefore, the demand for well-trained, educated practitioners must increase to fit the need. Conditions such as intellectual developmental disorder, Down syndrome, and autism spectrum disorder are more readily encountered in dental settings. However, it is equally appropriate to identify management techniques for patients with less common conditions. A case is reported in which a 38-year-old Caucasian male with a history significant for acrometageria and associated signs of Mallampati Class IV, micrognathia, decreased mouth opening, decreased thyromental distance, and decreased cervical range of motion presented for routine dental treatment under intravenous sedation. Providers should recognize appropriate management techniques to safely and effectively care for a wide patient demographic. PMID- 26260732 TI - Southern Dietary Pattern is Associated With Hazard of Acute Coronary Heart Disease in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. AB - BACKGROUND: The association of overall diet, as characterized by dietary patterns, with risk of incident acute coronary heart disease (CHD) has not been studied extensively in samples including sociodemographic and regional diversity. METHODS AND RESULTS: We used data from 17 418 participants in Reasons for Geographic and Racial Differences in Stroke (REGARDS), a national, population based, longitudinal study of white and black adults aged >=45 years, enrolled from 2003 to 2007. We derived dietary patterns with factor analysis and used Cox proportional hazards regression to examine hazard of incident acute CHD events - nonfatal myocardial infarction and acute CHD death - associated with quartiles of consumption of each pattern, adjusted for various levels of covariates. Five primary dietary patterns emerged: Convenience, Plant-based, Sweets, Southern, and Alcohol and Salad. A total of 536 acute CHD events occurred over a median (interquartile range) 5.8 (2.1) years of follow-up. After adjustment for sociodemographics, lifestyle factors, and energy intake, highest consumers of the Southern pattern (characterized by added fats, fried food, eggs, organ and processed meats, and sugar-sweetened beverages) experienced a 56% higher hazard of acute CHD (comparing quartile 4 with quartile 1: hazard ratio, 1.56; 95% confidence interval, 1.17-2.08; P for trend across quartiles=0.003). Adding anthropometric and medical history variables to the model attenuated the association somewhat (hazard ratio, 1.37; 95% confidence interval, 1.01-1.85; P=0.036). CONCLUSIONS: A dietary pattern characteristic of the southern United States was associated with greater hazard of CHD in this sample of white and black adults in diverse regions of the United States. PMID- 26260733 TI - Randomized, Controlled Trial of the Safety and Effectiveness of a Contact Force Sensing Irrigated Catheter for Ablation of Paroxysmal Atrial Fibrillation: Results of the TactiCath Contact Force Ablation Catheter Study for Atrial Fibrillation (TOCCASTAR) Study. AB - BACKGROUND: Contact force (CF) is a major determinant of lesion size and transmurality and has the potential to improve efficacy of atrial fibrillation ablation. This study sought to evaluate the safety and effectiveness of a novel irrigated radiofrequency ablation catheter that measures real-time CF in the treatment of patients with paroxysmal atrial fibrillation. METHODS AND RESULTS: A total of 300 patients with symptomatic, drug-refractory, paroxysmal atrial fibrillation were enrolled in a prospective, multicenter, randomized, controlled trial and randomized to radiofrequency ablation with either a novel CF-sensing catheter or a non-CF catheter (control). The primary effectiveness end point consisted of acute electrical isolation of all pulmonary veins and freedom from recurrent symptomatic atrial arrhythmia off all antiarrhythmic drugs at 12 months. The primary safety end point included device-related serious adverse events. End points were powered to show noninferiority. All pulmonary veins were isolated in both groups. Effectiveness was achieved in 67.8% and 69.4% of subjects in the CF and control arms, respectively (absolute difference, -1.6%; lower limit of 1-sided 95% confidence interval, -10.7%; P=0.0073 for noninferiority). When the CF arm was stratified into optimal CF (>=90% ablations with >=10 g) and nonoptimal CF groups, effectiveness was achieved in 75.9% versus 58.1%, respectively (P=0.018). The primary safety end point occurred in 1.97% and 1.40% of CF patients and control subjects, respectively (absolute difference, 0.57%; upper limit of 1-sided 95% confidence interval, 3.61%; P=0.0004 for noninferiority). CONCLUSIONS: The CF ablation catheter met the primary safety and effectiveness end points. Additionally, optimal CF was associated with improved effectiveness. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01278953. PMID- 26260734 TI - Examining Dietary Patterns in Relation to Chronic Disease: Matching Measures and Methods to Questions of Interest. PMID- 26260735 TI - Demonstrating the Value of Contact Force Sensing: More Difficult Than Meets the Eye. PMID- 26260736 TI - Major Depressive Disorder and Bipolar Disorder Predispose Youth to Accelerated Atherosclerosis and Early Cardiovascular Disease: A Scientific Statement From the American Heart Association. AB - In the 2011 "Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents," several medical conditions among youth were identified that predispose to accelerated atherosclerosis and early cardiovascular disease (CVD), and risk stratification and management strategies for youth with these conditions were elaborated. Major depressive disorder (MDD) and bipolar disorder (BD) among youth satisfy the criteria set for, and therefore merit inclusion among, Expert Panel tier II moderate-risk conditions. The combined prevalence of MDD and BD among adolescents in the United States is ~10%, at least 10 times greater than the prevalence of the existing moderate-risk conditions combined. The high prevalence of MDD and BD underscores the importance of positioning these diseases alongside other pediatric diseases previously identified as moderate risk for CVD. The overall objective of this statement is to increase awareness and recognition of MDD and BD among youth as moderate-risk conditions for early CVD. To achieve this objective, the primary specific aims of this statement are to (1) summarize evidence that MDD and BD are tier II moderate risk conditions associated with accelerated atherosclerosis and early CVD and (2) position MDD and BD as tier II moderate-risk conditions that require the application of risk stratification and management strategies in accordance with Expert Panel recommendations. In this scientific statement, there is an integration of the various factors that putatively underlie the association of MDD and BD with CVD, including pathophysiological mechanisms, traditional CVD risk factors, behavioral and environmental factors, and psychiatric medications. PMID- 26260737 TI - Post-operative monitoring of free muscle transfers by Laser Doppler Imaging: A prospective study. AB - PURPOSE: Despite different existing methods, monitoring of free muscle transfer is still challenging. In the current study we evaluated our clinical setting regarding monitoring of such tissues, using a recent microcirculation-imaging camera (EasyLDI) as an additional tool for detection of perfusion incompetency. PATIENTS AND METHODS: This study was performed on seven patients with soft tissue defect, who underwent reconstruction with free gracilis muscle. Beside standard monitoring protocol (clinical assessment, temperature strips, and surface Doppler), hourly EasyLDI monitoring was performed for 48 hours. Thereby a baseline value (raised flap but connected to its vascular bundle) and an ischaemia perfusion value (completely resected flap) were measured at the same point. RESULTS: The mean age of the patients, mean baseline value, ischaemia value perfusion were 48.00 +/- 13.42 years, 49.31 +/- 17.33 arbitrary perfusion units (APU), 9.87 +/- 4.22 APU, respectively. The LDI measured values in six free muscle transfers were compatible with hourly standard monitoring protocol, and normalized LDI values significantly increased during time (P < 0.001, r = 0.412). One of the flaps required a return to theatre 17 hours after the operation, where an unsalvageable flap loss was detected. All normalized LDI values of this flap were under the ischaemia perfusion level and the trend was significantly descending during time (P < 0.001, r = -0.870). CONCLUSION: Due to the capability of early detection of perfusion incompetency, LDI may be recommended as an additional post-operative monitoring device for free muscle flaps, for early detection of suspected failing flaps and for validation of other methods. PMID- 26260738 TI - Benign orbital angiomatous tumors with intracranial extension. AB - Orbital neoplasms with associated bone erosions and intracranial extension are generally considered suspicious for malignancies. Here, we describe the clinical and radiological findings, as well as the surgical management of two extraordinary cases, in which such bony perforations with subsequent intracranial tumor growth resulted from benign angiomatous orbital neoplasms. Two female patients, 69 years old (case 1) and 51 years old (case 2), had both developed visual symptoms (visual field restrictions and/or visual acuity loss) over several months. Computed tomography revealed an orbital tumor of the anterosuperior orbit with painless swelling of the medial upper eyelid of the right eye in case 1, and a posterior intraconal tumor close to the orbital apex of the left eye in case 2, respectively. In both cases, the tumor was associated with a perforation of the orbital roof connecting the orbit with the anterior cranial fossa. An interdisciplinary ophthalmologic and neurosurgical approach allowed for complete tumor removal, in both patients with no signs for local recurrence during the subsequent follow-up of 15 and 18 months, respectively, as well as for a satisfactory visual rehabilitation. PMID- 26260739 TI - Speeding up the product release: a second-sphere contribution from Tyr191 to the reactivity of L-lactate oxidase revealed in crystallographic and kinetic studies of site-directed variants. AB - Among alpha-hydroxy acid-oxidizing flavoenzymes l-lactate oxidase (LOX) is unique in featuring a second-sphere tyrosine (Tyr191 in Aerococcus viridans LOX; avLOX) at the binding site for the substrate's carboxylate group. Y191F, Y191L and Y191A variants of avLOX were constructed to affect a hydrogen-bond network connecting Tyr191 to the carboxylate of the bound ligand via the conserved Tyr40 and to examine consequent effects on enzymatic reactivity. Kinetic studies at 20 degrees C and pH 6.5 revealed that release of pyruvate product was decreased 4.7 fold (Y191F), 19-fold (Y191L) and 28-fold (Y191A) compared with wild-type enzyme (~ 141 s(-1)) and thus became mainly rate limiting for l-lactate oxidation by the variants at a steady-state under air-saturated conditions. In the Y191L and the Y191A variants, but not in the Y191F variant, l-lactate binding was also affected strongly by the site-directed substitution. Reduction of the flavin cofactor by l lactate and its reoxidation by molecular oxygen were, however, comparatively weakly affected by the replacements of Tyr191. Unlike the related lactate monooxygenase, which prevents the fast dissociation of pyruvate to promote its oxidative decarboxylation by H2 O2 into acetate, CO2 and water as final reaction products, all avLOX variants retained their native oxidase activity where catalytic turnover results in the equivalent formation of H2O2. The 1.9 A crystal structure of the Y191F variant bound with FMN and pyruvate revealed a strictly locally disruptive effect of the site-directed substitution. Product off-rates appear to be dictated by partitioning of residues including Tyr191 from an active site lid loop into bulk solvent and modulation of the hydrogen bond strength that links Tyr40 with the pyruvate's carboxylate group. Overall, this study emphasizes the possibly high importance of contributions from second-sphere substrate binding residues to the fine-tuning of reactivity in alpha-hydroxy acid-oxidizing flavoenzymes, requiring that the catalytic steps of flavin reduction and oxidation are properly timed with the physical step of alpha-keto acid product release. PMID- 26260740 TI - Thrombotic thrombocytopenic purpura during pregnancy versus imitator of preeclampsia. AB - BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a severe disorder affecting the microcirculation of multiple organs due to a systemic endothelial cell injury secondary to a deficiency in ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) activity. TTP is a rare complication of pregnancy with a poor prognosis and high fetal mortality, especially when it occurs during the first trimester. Recent data have supported that effective treatment of TTP is plasma therapy. Unfortunately a major problem remains in the delay in diagnosis due to confounding factors between other "imitators of preeclampsia." Rapid and readily available laboratory testing to quickly diagnose TTP is desperately needed to improve care and to save mother and future child life. CASE REPORT: We describe a rare case of successful pregnancy after TTP manifestations occurring in the first trimester; most importantly, our experience represents the first case of atypical manifestation due to neurologic and kidney manifestations preceding laboratory assay alterations. RESULTS: We treated a patient with plasma replacement of 30 mL/kg/day and daily plasmapheresis in combination with continuous infusion of fresh-frozen plasma 10 mL/kg/day. The response of clinical manifestation immediately improved. At 30 weeks, the patient had multiple episodes of high blood pressure and concomitant decrease of hemoglobin and platelet count, so a cesarean section was immediately performed. She delivered a healthy female baby. CONCLUSION: Early diagnosis by ADAMTS13 activity, occasionally occurring before clinical manifestations, aided us in promptly administering commended and life-saving treatments. PMID- 26260742 TI - Editorial Comment. PMID- 26260741 TI - Differential tissue accumulation of 2,3,7,8-Tetrachlorinated dibenzo-p-dioxin in Arabidopsis thaliana affects plant chronology, lipid metabolism and seed yield. AB - BACKGROUND: Dioxins are one of the most toxic groups of persistent organic pollutants. Their biotransmission through the food chain constitutes a potential risk for human health. Plants as principal actors in the food chain can play a determinant role in removing dioxins from the environment. Due to the lack of data on dioxin/plant research, this study sets out to determine few responsive reactions adopted by Arabidopsis plant towards 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD), the most toxic congener of dioxins. RESULTS: Using a high resolution gas chromatography/mass spectrometry, we demonstrated that Arabidopsis plant uptakes TCDD by the roots and accumulates it in the vegetative parts in a tissue-specific manner. TCDD mainly accumulated in rosette leaves and mature seeds and less in stem, flowers and immature siliques. Moreover, we observed that plants exposed to high doses of TCDD exhibited a delay in flowering and yielded fewer seeds of a reduced oil content with a low vitality. A particular focus on the plant fatty acid metabolism showed that TCDD caused a significant reduction in C18-unsaturated fatty acid level in plant tissues. Simultaneously, TCDD induced the expression of 9-LOX and 13-LOX genes and the formation of their corresponding hydroperoxides, 9- and 13-HPOD as well as 9- or 13-HPOT, derived from linoleic and linolenic acids, respectively. CONCLUSIONS: The current work highlights a side of toxicological effects resulting in the administration of 2,3,7,8-TCDD on the Arabidopsis plant. Similarly to animals, it seems that plants may accumulate TCDD in their lipids by involving few of the FA-metabolizing enzymes for sculpting a specific oxylipins "signature" typified to plant TCDD tolerance. Together, our results uncover novel responses of Arabidopsis to dioxin, possibly emerging to overcome its toxicity. PMID- 26260743 TI - Reply: To PMID 26142714. PMID- 26260744 TI - Thyroid disorders and gastrointestinal and liver dysfunction: A state of the art review. AB - Thyroid disorders commonly impact on the gastrointestinal system and may even present with gastrointestinal symptoms in isolation; for example, metastatic medullary thyroid carcinoma typically presents with diarrhoea. Delays in identifying and treating the underlying thyroid dysfunction may lead to unnecessary investigations and treatment, with ongoing morbidity, and can potentially be life-threatening. Similarly, gastrointestinal diseases can impact on thyroid function tests, and an awareness of the concept and management of non thyroidal illness is necessary to avoid giving unnecessary thyroid therapies that could potentially exacerbate the underlying gastrointestinal disease. Dual thyroid and gastrointestinal pathologies are also common, with presentations occurring concurrently or sequentially, the latter after a variable time lag that can even extend over decades. Such an association aetiologically relates to the autoimmune background of many thyroid disorders (e.g. Graves' disease and Hashimoto's thyroiditis) and gastrointestinal disorders (e.g. coeliac disease and inflammatory bowel disease); such autoimmune conditions can sometimes occur in the context of autoimmune polyglandular syndrome. Emphasis should also be given to the gastrointestinal side effects of some of the medications used for thyroid disease (e.g. anti-thyroid drugs causing hepatotoxicity) and vice versa (e.g. interferon therapy causing autoimmune thyroid dysfunction). In this review, we discuss disorders of the thyroid-gut axis and identify the evidence base behind the management of such disorders. PMID- 26260745 TI - Epidemiological changes in tinea capitis over the sixty years of economic growth in China. AB - BACKGROUND: Tinea capitis is a fungal infection of the scalp occurring commonly in children. Historical data indicate that clinical manifestations and the spectrum of etiologic agents vary greatly with geography, as well as socioeconomic affected populations. OBJECTIVE: To study the possible connection between socioeconomic status, the disease patterns and the variability of etiological agents. METHODS: We reviewed tinea capitis in China through literature since 1956. The disease pattern was correlated with economic and public health management protocols. Historical data on fungal identification were mostly obtained by morphology. The accuracy of these historical results was further confirmed by use of both morphological and ITS identification on a control set of 90 isolates collected recently from local hospital. RESULTS: Full agreement of the two identification methods implies that data from the literature were sufficiently reliable to allow comparison across reported cases. In sum, 88 papers involving 25 administrative provinces and municipalities with 38,962 clinical strains met the inclusion criteria of this review. Zoophilic species Microsporum canis is the most prevalent agent within large, modernized cities in China today accounting for over 80% of infections. In contrast, anthropophilic dermatophytes, particularly Trichophyton violaceum, are geographically endemic only in some southeastern and northwestern regions. CONCLUSION: Economic development and urbanization of cities favor a shift of etiological agents from anthroponoses to zoonoses in contemporary China. Pets are becoming the most likely sources of infection in modern lifestyles, replacing the earlier human-to human transmission mode. However, the latter transmission mode is still prevalent in less developed areas lacking adequate social and public health facilities. PMID- 26260746 TI - In vitro antifungal synergy between amphiphilic aminoglycoside K20 and azoles against Candida species and Cryptococcus neoformans. AB - Several azoles are widely used to treat human fungal infections. Increasing resistance to these azoles has prompted exploration of their synergistic antifungal activities when combined with other agents. The amphiphilic aminoglycoside, K20, was recently shown to inhibit filamentous fungi, yeasts and heterokonts, but not bacteria. In this study, in vitro synergistic growth inhibition by combinations of K20 and azoles (fluconazole, itraconazole, voriconazole, clotrimazole, or posaconazole) were examined against Candida species and Cryptococcus neoformans. Checkerboard microbroth dilution, time-kill curve, and disk diffusion assays revealed that K20 has synergistic inhibitory activities with all five azoles against C. albicans including azole-resistant C. albicans strains ATCC 64124 and ATCC 10231. Four (fluconazole, itraconazole, clotrimazole, posaconazole) and three (fluconazole, itraconazole, voriconazole) azoles were synergistically inhibitory with K20 against C. lusitaniae and C. tropicalis, respectively. Only posaconazole showed synergy with K20 against two Cryptococcus neoformans strains (90-26 and VR-54). Time-kill curves with azole resistant C. albicans 64124 and azole-sensitive C. albicans MYA-2876 confirmed the K20-azole synergistic interactions with a >= 2 log10 decrease in colony forming units (CFU)/ml compared with the corresponding azoles alone. These results suggest that combinations of K20 and azoles offer a possible strategy for developing therapies against candidiasis. PMID- 26260747 TI - 3,4,5-Trimethoxycinnamic acid, one of the constituents of Polygalae Radix exerts anti-seizure effects by modulating GABAAergic systems in mice. AB - Polygalae Radix is an important medicinal plant that is widely used in most of Africa. 3,4,5-Trimethoxycinnamic acid (TMCA) is one of the constituents of Polygalae Radix. Until now, the mechanisms involved in the anti-seizure property of TMCA are still unclear. We examined the anti-seizure effect of TMCA. TMCA administered at doses of 5, 10 and 20 mg/kg and evaluated anti-seizure effects by maximal electroshock (MES) and pentylenetetrazol (PTZ) models in mice. TMCA administered at doses of 10 and 20 mg/kg significantly reduced the incidence of MES-induced tonic hindlimb extension (THE). TMCA significantly delayed the onset of myoclonic jerks (MJ), and decreased the seizure severity and mortality compared with the vehicle-treated animals in PTZ seizure model. TMCA 10 and 20 mg/kg treated groups also did not determined generalized clonic seizures (GCS). Pretreatment with a GABAA/benzodiazepine (BZ) receptor antagonist flumazenil blocked the anti-seizure effects of TMCA. These data support the further investigation of TMCA as a GABAA/BZ receptor agonist for anti-seizure therapy. PMID- 26260748 TI - Genistein reduces the noxious effects of in utero bisphenol A exposure on the rat prostate gland at weaning and in adulthood. AB - Bisphenol A (BPA) is one hormonally active chemical with potential deleterious effects on reproductive organs, including breast and prostate. In contrast, genistein (GEN) is the major phytoestrogen of soy that presents potential protective effects against hormone-dependent cancers, including that of the prostate. Thus, pregnant Sprague-Dawley rats were treated with BPA at 25 or 250 MUg/kg/day by gavage from gestational day (GD) 10-21 with or without dietary GEN at 250 mg/kg/chow (~5.5 mg/kg/day). Then, male offspring from different litters were euthanized on post-natal day (PND) 21 and 180. At PND21, BPA 25 exposure induced early prostatic changes while dietary GEN attenuated some deleterious actions this xenoestrogen on epithelial cell proliferation levels, androgen receptor expression and prostatic architecture in male offspring. At PND180, a significant increase in incidence of prostatic multifocal inflammation/reactive hyperplasia and atypical hyperplasia were observed in male offspring from dams that received BPA 25. On the other hand, maternal GEN feeding attenuated some the adverse effects of BPA 25 on prostate disease at late-in-life. This way, the present findings point to preventive action of dietary GEN on deleterious effects of gestational BPA exposure in both early and late prostate development in offspring F1. PMID- 26260749 TI - Morphological and release characterization of nanoparticles formulated with poly (dl-lactide-co-glycolide) (PLGA) and lupeol: In vitro permeability and modulator effect on NF-kappaB in Caco-2 cell system stimulated with TNF-alpha. AB - Lupeol exhibits anti-inflammatory effects; unfortunately it shows low water solubility. An alternative to overcome this is the development of nanomaterials. Several methods for nanomaterial production are available. One of them is emulsification/solvent-evaporation. The objective of the present work was to evaluate physical properties, transport and in vitro modulator effects on NF kappaB of poly (lactide-co-glycolide) (PLGA) nanoparticles loaded with lupeol. Nanonutraceuticals were prepared with 16% (w/v) of lupeol. Size distribution and morphology were measured by particle size analyzer and TEM. In vitro release of lupeol was studied by three different models: Higuchi, Siepmann & Peppas, and Power law. Transport of nanonutraceutical was studied in a Caco-2 cell model and by GC-MS. Modulator effect on NK-kappaB was studied by western blot analysis. Nanonutraceuticals were 10% larger than the nanoparticles without lupeol (372 vs 337 nm) and presented a broader size distribution (0.28 vs 0.22). TEM results displayed spherical structures with a broader size distribution. Entrapment efficiency of lupeol was 64.54% and it in vitro release data fitted well to the Power law and Higuchi equation (R > 0.84-0.84). Strong regulation of NF-kappaB of nanonutraceutical was observed. It was not observed any transport across the Caco 2 cell model at the different experimental conditions. PMID- 26260750 TI - Acute and subacute pulmonary toxicity and mortality in mice after intratracheal instillation of ZnO nanoparticles in three laboratories. AB - Inhalation is the main pathway of ZnO exposure in the occupational environment but only few studies have addressed toxic effects after pulmonary exposure to ZnO nanoparticles (NP). Here we present results from three studies of pulmonary exposure and toxicity of ZnO NP in mice. The studies were prematurely terminated because interim results unexpectedly showed severe pulmonary toxicity. High bolus doses of ZnO NP (25 up to 100 MUg; >=1.4 mg/kg) were clearly associated with a dose dependent mortality in the mice. Lower doses (>=6 MUg; >=0.3 mg/kg) elicited acute toxicity in terms of reduced weight gain, desquamation of epithelial cells with concomitantly increased barrier permeability of the alveolar/blood as well as DNA damage. Oxidative stress was shown via a strong increase in lipid peroxidation and reduced glutathione in the pulmonary tissue. Two months post exposure revealed no obvious toxicity for 12.5 and 25 MUg on a range of parameters. However, mice that survived a high dose (50 MUg; 2.7 mg/kg) had an increased pulmonary collagen accumulation (fibrosis) at a similar level as a high bolus dose of crystalline silica. The recovery from these toxicological effects appeared dose-dependent. The results indicate that alveolar deposition of ZnO NP may cause significant adverse health effects. PMID- 26260751 TI - Inverse relationship between elemental selenium nanoparticle size and inhibition of cancer cell growth in vitro and in vivo. AB - Elemental selenium nanoparticles (SeNPs) have been demonstrated to be equivalent to selenomethionine and methylselenocysteine in upregulating selenoenzymes; however, the toxicity of SeNPs is markedly lower than these two organic selenium compounds. The objective of this study was to determine the effect of SeNP size on cancer cell growth and ascertain whether production of reactive oxygen species (ROS) is implicated as a candidate mechanism of action. Two types of SeNPs (averaging 35 nm and 91 nm) were investigated. Cell accumulation was inhibited in vitro and in vivo in a manner inversely proportional to particle size. In vitro modeling experiments showed the reduction of SeNPs to be glutathione concentration dependent and to result in ROS formation. Both SeNP biotransformation and ROS production were size dependent, with the smaller SeNPs being more active, thereby suggesting that small-sized SeNPs are more effective in inhibiting cancer cell proliferation through an ROS mediated mechanism. PMID- 26260752 TI - Risk Factors for Hepatitis C Virus (HCV) Infection in Areas with a High Prevalence of HCV in the Republic of Korea in 2013. AB - BACKGROUND/AIMS: The prevalence of hepatitis C virus (HCV) infection in Busan, Gyeongnam, and Jeonnam Provinces in Korea is more than twice the national average. This study aimed to examine whether demographic and lifestyle characteristics are associated with HCV infection in these areas. METHODS: A case control study was performed at three study hospitals. HCV cases were matched with two controls for sex and age. Patient controls were selected from non-HCV patients at the same hospital. Healthy controls were subjects participating in medical checkups. Conditional logistic regression models were used. RESULTS: A total of 234 matched-case and patient- and healthy-control pairs were analyzed. The significant risk factors for both controls were sharing razors (adjusted odds ratio [aOR], 2.39 and 3.29, respectively) and having more than four lifetime sexual partners (aOR, 2.15 and 6.89, respectively). Contact dockworkers (aOR, 1.91) and tattoos (aOR, 2.20) were significant risk factors for the patient controls. Transfusion (aOR, 5.38), a bloody operation (aOR, 5.02), acupuncture (aOR, 2.08), and piercing (aOR, 5.95) were significant risk factors for the healthy controls. Needle stick injuries and intravenous drug abuse were significant in the univariate analysis. CONCLUSIONS: More education concerning the dangers of sharing razors, tattoos and piercings is required to prevent HCV infection. More attention should be paid to needle stick injuries in hospitals and the community. PMID- 26260753 TI - Incidence and Clinical Outcomes of Clostridium difficile Infection after Treatment with Tuberculosis Medication. AB - BACKGROUND/AIMS: To determine the incidence and clinical characteristics of tuberculosis (TB) medication-associated Clostridium difficile infection. METHODS: This multicenter study included patients from eight tertiary hospitals enrolled from 2008 to 2013. A retrospective analysis was conducted to identify the clinical features of C. difficile infection in patients who received TB medication. RESULTS: C. difficile infection developed in 54 of the 19,080 patients prescribed TB medication, representing a total incidence of infection of 2.83 cases per 1,000 adults. Fifty-one of the 54 patients (94.4%) were treated with rifampin. The patients were usually treated with oral metronidazole, which produced improvement in 47 of the 54 patients (87%). Twenty-three patients clinically improved with continuous rifampin therapy for C. difficile infection. There were no significant differences in improvement between patients treated continuously (n=21) and patients in whom treatment was discontinued (n=26). CONCLUSIONS: The incidence of C. difficile infection after TB medication was not low considering the relatively low TB medication dosage compared to other antibiotics. It may not be always necessary to discontinue TB medication. Instead, decisions concerning discontinuation of TB medication should be based on TB status. PMID- 26260754 TI - Does Polyethylene Glycol (PEG) Plus Ascorbic Acid Induce More Mucosal Injuries than Split-Dose 4-L PEG during Bowel Preparation? AB - BACKGROUND/AIMS: The aims of this study were to compare the bowel-cleansing efficacy, patient affinity for the preparation solution, and mucosal injury between a split dose of polyethylene glycol (SD-PEG) and low-volume PEG plus ascorbic acid (LV-PEG+Asc) in outpatient scheduled colonoscopies. METHODS: Of the 319 patients, 160 were enrolled for SDPEG, and 159 for LV-PEG+Asc. The bowel cleansing efficacy was rated according to the Ottawa bowel preparation scale. Patient affinity for the preparation solution was assessed using a questionnaire. All mucosal injuries observed during colonoscopy were biopsied and histopathologically reviewed. RESULTS: There was no significant difference in bowel cleansing between the groups. The LV-PEG+Asc group reported better patient acceptance and preference. There were no significant differences in the incidence or characteristics of the mucosal injuries between the two groups. CONCLUSIONS: Compared with SD-PEG, LV-PEG+Asc exhibited equivalent bowel-cleansing efficacy and resulted in improved patient acceptance and preference. There was no significant difference in mucosal injury between SD-PEG and LV-PEG+Asc. Thus, the LV-PEG+Asc preparation could be used more effectively and easily for routine colonoscopies without risking significant mucosal injury. PMID- 26260755 TI - Prevalence and Factors Associated with Nonalcoholic Fatty Liver Disease in a Nonobese Korean Population. AB - BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is an emerging problem in Asia, but little is known about the disease in the nonobese population. The aims of this study were to investigate the prevalence of NAFLD and the factors associated with it in a nonobese Korean population and to compare the clinical characteristics of nonobese and obese subjects with NAFLD. METHODS: This cross sectional study used data from 2,058 subjects who participated in a medical checkup program. RESULTS: The prevalence of NAFLD was 12.4% (213/1,711) in the nonobese population. A higher body mass index (BMI), higher homeostasis model assessment of insulin resistance (HOMA-IR) values, higher alanine aminotransferase (ALT) levels, triglyceride concentrations >=150 mg/dL, and hyperuricemia were independently associated with the presence of NAFLD in the nonobese subjects. Compared with the obese subjects with NAFLD, the nonobese subjects with NAFLD were composed of a higher proportion of females and had lower BMIs, smaller waist circumferences, lower HOMA-IR values, and fewer metabolic irregularities. CONCLUSIONS: Higher BMIs, HOMA-IR values, ALT levels, hypertriglyceridemia, and hyperuricemia were associated with NAFLD in the nonobese subjects. Clinicians should be particularly aware of the possibility of NAFLD in nonobese Asian people. PMID- 26260756 TI - Visceral Obesity Is Associated with Gallbladder Polyps. AB - BACKGROUND/AIMS: Gallbladder polyps (GBP) are a common clinical finding and may possess malignant potential. We conducted this study to determine whether visceral obesity is a risk factor for GBP. METHODS: We retrospectively reviewed records of subjects who received both ultrasonography and computed tomography with measurements of the areas of visceral adipose tissue and total adipose tissue (TAT) on the same day as health checkups. RESULTS: Ninety-three of 1,615 subjects (5.8%) had GBP and were compared with 186 age- and sex-matched controls. VAT (odds ratio [OR], 2.941; 95% confidence interval [CI], 1.325 to 6.529; p=0.008 for the highest quartile vs. the lowest quartile) and TAT (OR, 3.568; 95% CI, 1.625 to 7.833; p=0.002 for the highest quartile vs. the lowest quartile) were independent risk factors together with hypertension (OR, 2.512; 95% CI, 1.381 to 4.569; p=0.003), diabetes mellitus (OR, 2.942; 95% CI, 1.061 to 8.158; p=0.038), hepatitis B virus positivity (OR, 3.548; 95% CI, 1.295 to 9.716; p=0.014), and a higher level of total cholesterol (OR, 2.232; 95% CI, 1.043 to 4.778; p=0.039 for. CONCLUSIONS: Visceral obesity measured by VAT and TAT was associated with GBP irrespective of body mass index or waist circumference. PMID- 26260757 TI - Endoscopic Findings of Enteropathy-Associated T-Cell Lymphoma Type II: A Case Series. AB - Enteropathy-associated T-cell lymphoma (EATL) is a rare extranodal T-cell lymphoma arising from the intestine. Two types of EATL have been reported. In contrast to the classic EATL type I, EATL type II occurs sporadically, is unrelated to celiac disease, and comprises 10% to 20% of all EATL cases. A total of five cases of EATL type II were diagnosed at our clinic from January 2009 to September 2012. Four of the five patients were diagnosed with the help of endoscopy. Among the four patients, two of the cases involved both the small and large intestines, whereas in the other two patients, EATL was limited to the small intestine. Common endoscopic findings included innumerable fine granularities (also called mosaic mucosal patterns) and diffuse thickening of the mucosa with a semicircular shallow ulceration in the lesions of the small bowel. In contrast, the endoscopic findings of the colon were nonspecific and could not distinguish EATL type II from other diseases. There are only few published reports regarding the representative endoscopic findings of EATL. Here, we present the clinical and endoscopic findings of four cases of EATL type II diagnosed by endoscopy. PMID- 26260758 TI - Hydroxychloroquine neuromyotoxicity: a case with rapid course and complete recovery. PMID- 26260759 TI - Endovascular treatment of cerebellar arteriovenous malformations: management of associated aneurysms first or later. AB - The purpose of this study was to determine the safety and effectiveness of cerebellar arteriovenous malformations (AVMs) embolization and find out the suitable methods to manage associated aneurysms. Medical records of all patients between 1997 and 2014 with a diagnosis of cerebellar AVMs were retrospectively reviewed. Univariable and multivariable logistic analysis were used to assess AVMs characteristics to calculate for the risk of hemorrhage. Endovascular treatment was the main treatment measure to manage the AVMs and associated aneurysms. Of 142 patients, 115 (81.0 %) presented with hemorrhage and 42 (29.6 %) with associated aneurysms. A significant association with cerebellar AVMs hemorrhage was found for small size, prenidal aneurysms, and deep venous drainage in the univariable and multivariable analysis. Associated aneurysms were treated firstly in 41 patients except for 1 patient with 2 prenidal and 2 intranidal aneurysms. The special case was dealt with AVMs and 2 intranidal aneurysms first and angiography showed that the 2 prenidal associated aneurysms disappeared with time. Hemorrhage appeared in 13/142 patients (9.2 %) during the follow-up period, none of which was with associated aneurysms. Endovascular treatment can be a feasible way for treating cerebellar AVMs. Intranidal associated aneurysms should be treated first. Prenidal associated aneurysms can be treated later depending on the angioarchitecture of AVMs. PMID- 26260760 TI - The organization of domains in proteins obeys Menzerath-Altmann's law of language. AB - BACKGROUND: The combination of domains in multidomain proteins enhances their function and structure but lengthens the molecules and increases their cost at cellular level. METHODS: The dependence of domain length on the number of domains a protein holds was surveyed for a set of 60 proteomes representing free-living organisms from all kingdoms of life. Distributions were fitted using non-linear functions and fitted parameters interpreted with a formulation of decreasing returns. RESULTS: We find that domain length decreases with increasing number of domains in proteins, following the Menzerath-Altmann (MA) law of language. Highly significant negative correlations exist for the set of proteomes examined. Mathematically, the MA law expresses as a power law relationship that unfolds when molecular persistence P is a function of domain accretion. P holds two terms, one reflecting the matter-energy cost of adding domains and extending their length, the other reflecting how domain length and number impinges on information and biophysics. The pattern of diminishing returns can therefore be explained as a frustrated interplay between the strategies of economy, flexibility and robustness, matching previously observed trade-offs in the domain makeup of proteomes. Proteomes of Archaea, Fungi and to a lesser degree Plants show the largest push towards molecular economy, each at their own economic stratum. Fungi increase domain size in single domain proteins while reinforcing the pattern of diminishing returns. In contrast, Metazoa, and to lesser degrees Protista and Bacteria, relax economy. Metazoa achieves maximum flexibility and robustness by harboring compact molecules and complex domain organization, offering a new functional vocabulary for molecular biology. CONCLUSIONS: The tendency of parts to decrease their size when systems enlarge is universal for language and music, and now for parts of macromolecules, extending the MA law to natural systems. PMID- 26260761 TI - Nutrition in remote Aboriginal communities: lessons from Mai Wiru and the Anangu Pitjantjatjara Yankunytjatjara Lands. AB - OBJECTIVE: To examine the impact of efforts to improve nutrition on the Anangu Pitjantjatjara Yankunytjatjara (APY) Lands from 1986, especially in Mai Wiru (good food) stores. METHODS: Multiple methods were employed. Literature was searched systematically. In 2012, the store-turnover method quantified dietary intake of the five APY communities that have a Mai Wiru store. The price of a standard market basket of basic foods, implementation of store nutrition policy requirements and healthy food checklists were also assessed in all seven APY community stores at intervals from 2012. Results were compared with available data from 1986. RESULTS: Despite concerted efforts and marked achievements, including decreased intake of sugar, increased availability and affordability of healthy foods (particularly fruit and vegetables) and consequent improvement in some nutrient intakes, the overall effect has been a decrease in total diet quality since 1986. This is characterised by increased supply and intake of discretionary foods high in saturated fat, added sugar and salt, particularly sugar sweetened beverages, convenience meals and take-away foods. CONCLUSIONS: The documented improvements confirm that residing in these communities can help Aboriginal residents exert control over key aspects of their food supply. However, the overall findings reflect broader changes to the general Australian food supply, and reinforce the notion that, in the absence of supportive regulation and market intervention, adequate and sustained resources are required to improve nutrition and prevent diet-related chronic disease on the APY Lands. IMPLICATIONS: This study also provides insights into food supply/security issues affecting other remote communities and wider Australia. PMID- 26260762 TI - Bone: Targeting myostatin could prevent bone destruction in inflammatory arthritis. PMID- 26260763 TI - Therapy. Optimized treatment algorithms for digital vasculopathy in SSc. AB - Early identification of secondary Raynaud phenomenon is essential to treat the underlying disease-most frequently systemic sclerosis (SSc). Integrated therapeutic approaches and monitoring systems that offer improved modalities of care feature in the new best practice recommendations for the treatment of digital vasculopathy in SSc. PMID- 26260764 TI - Calcifying ghost cell odontogenic tumor (CGCOT) with predominance of clear cells: a case report with important diagnostic considerations. AB - An 18-year-old female reported painful swelling in the left maxillary region 4 months after the extraction of tooth #15. Because incisional biopsy suggested ameloblastoma with clear-cell changes, segmental resection was performed. The microscopic examination of the excised tissue revealed histomorphologic diversity, with features of typical calcifying ghost cell odontogenic tumor (CGCOT) and a significant clear-cell component constituting more than 50% of the tumor mass without any features of malignancy. Clear cells were periodic acid Schiff (PAS) positive and mucicarmine negative. CK19 was strongly positive in the solid tumor islands and variably positive in clear cells. A definitive diagnosis of CGCOT with predominance of clear cells was confirmed. Because both squamous metaplasia and clear-cell components were present in the ameloblastic follicles independent of each other, the presence of abundant calcifications favored the diagnosis of CGCOT with a clear-cell component over that of an ameloblastoma with clear-cell changes. The importance of identifying the histomorphologic features of the 2 entities, ameloblastoma and CGCOT, is highlighted. This appears to be the second case reported in the literature, to the best of our knowledge. PMID- 26260765 TI - Mucosal melanoma of the head and neck: recurrence characteristics and survival outcomes. AB - OBJECTIVE: The aim of this study was to review oncologic outcomes and recurrence characteristics of head and neck mucosal melanomas (HNMMs) managed at a tertiary referral center. STUDY DESIGN: Clinical records of 10 patients who were managed for HNMMs between 2001 and 2013 were retrospectively analyzed. RESULTS: The median age was 66 years (range 28-76 years) and male/female (M/F) ratio was 1:5. The 3-year disease-free survival (DFS) rates and overall survival (OS) rates were 11.7% and 35%, respectively; and the 5-year DFS rates and OS rates 11.7% and 23.3%, respectively. The median DFS and OS periods were 12 months (range 2-36 months) and 17 months (range 7-96 months), respectively. The rates of development of local, regional, and systemic recurrences were 20%, 50%, and 80%, respectively. Lungs were involved in all patients who had distant metastasis. CONCLUSIONS: This study shows that HNMMs has a very aggressive course and that distant metastases are common. For this reason, systemic control of the disease is an important aim of treatment. PMID- 26260766 TI - Carotid calcifications on panoramic radiographs: a 5-year follow-up study. AB - OBJECTIVE: The aim of this study was to determine whether people with calcifications in the area of the carotid arteries on panoramic radiographs (CALPANs) have an increased prevalence of vascular risk factors or an increased risk of future vascular events. MATERIALS AND METHODS: We included 113 consecutive patients with CALPANs and 116 gender- and age-matched controls without CALPANs. Vascular risk factors were generally known in the study population, since it was recorded in a population-based community-screening program. RESULTS: Patients with CALPANs had a higher prevalence of vascular risk factors than controls independent of previous vascular events. During the 5.4 year follow-up, patients with CALPANs had a higher risk of a combined endpoint of vascular events (5.6%/yr) compared with the controls (2.4%/yr) (P = .004 by log rank test; unadjusted hazard ratio (HR) 2.4; 95% CI 1.3-4.3). This difference was not significant when previous vascular events and risk factors were taken into account (adjusted HR; 1.2; 95% CI 0.6-2.3; P = .62; Cox regression). CONCLUSIONS: People with CALPANs are very likely to have vascular risk factors, but these factors might be unknown when CALPANs are detected. Accordingly, patients with CALPANs should be advised to have their vascular risk factors regularly checked in order to receive advice on preventive lifestyle modifications and medical treatment when indicated. However, it remains unknown whether CALPANs add information about the independent risk of future vascular events. Therefore, further studies are warranted to investigate whether the detection of CALPANs indicates a need for additional or more intense vascular treatment. PMID- 26260767 TI - A quick eye to anger: An investigation of a differential effect of facial features in detecting angry and happy expressions. AB - Detection of angry and happy faces is generally found to be easier and faster than that of faces expressing emotions other than anger or happiness. This can be explained by the threatening account and the feature account. Few empirical studies have explored the interaction between these two accounts which are seemingly, but not necessarily, mutually exclusive. The present studies hypothesised that prominent facial features are important in facilitating the detection process of both angry and happy expressions; yet the detection of happy faces was more facilitated by the prominent features than angry faces. Results confirmed the hypotheses and indicated that participants reacted faster to the emotional expressions with prominent features (in Study 1) and the detection of happy faces was more facilitated by the prominent feature than angry faces (in Study 2). The findings are compatible with evolutionary speculation which suggests that the angry expression is an alarming signal of potential threats to survival. Compared to the angry faces, the happy faces need more salient physical features to obtain a similar level of processing efficiency. PMID- 26260768 TI - Metabolic engineering of Escherichia coli for the production of 1,3 diaminopropane, a three carbon diamine. AB - Bio-based production of chemicals from renewable resources is becoming increasingly important for sustainable chemical industry. In this study, Escherichia coli was metabolically engineered to produce 1,3-diaminopropane (1,3 DAP), a monomer for engineering plastics. Comparing heterologous C4 and C5 pathways for 1,3-DAP production by genome-scale in silico flux analysis revealed that the C4 pathway employing Acinetobacter baumannii dat and ddc genes, encoding 2-ketoglutarate 4-aminotransferase and L-2,4-diaminobutanoate decarboxylase, respectively, was the more efficient pathway. In a strain that has feedback resistant aspartokinases, the ppc and aspC genes were overexpressed to increase flux towards 1,3-DAP synthesis. Also, studies on 128 synthetic small RNAs applied in gene knock-down revealed that knocking out pfkA increases 1,3-DAP production. Overexpression of ppc and aspC genes in the pfkA deleted strain resulted in production titers of 1.39 and 1.35 g l(-1) of 1,3-DAP, respectively. Fed-batch fermentation of the final engineered E. coli strain allowed production of 13 g l( 1) of 1,3-DAP in a glucose minimal medium. PMID- 26260769 TI - Effects of pre-slaughter showering and ventilation on stress, meat quality and metabolite concentrations of broilers in summer. AB - Effects of pre-slaughter showering and ventilation on stress, meat quality and energy metabolism of broilers in summer were investigated. After transport, 84 Arbor Acres broilers were randomly divided into four treatment groups: (i) control group without ventilation and showering (C); (ii) 10 min ventilation without showering (VWS); (iii) 10 min showering without ventilation (SWV); (iv) 5 min showering and then 5 min ventilation (SV). Compared with the control group, plasma lactate dehydrogenase and creatine kinase activities in the other three treatment groups were (P < 0.05) lower; however, the plasma glucose level did not show any significant changes among all the groups. The breast meat in the SV group had significantly (P < 0.05) higher pHu , glycogen content, lower L*, DeltapH, drip loss, cook loss, R-value and lactate content than the control group; however, there was no significant difference in shear force values among all the groups. In conclusion, this study indicated broilers in the SV group showed a lower stress level and greater meat quality, which suggest that showering and ventilation after transportation may be a good measure to relieve stress caused by transport under high temperature and improve the meat quality of broilers. PMID- 26260770 TI - Genomic study of congenital insensitivity to pain provides new avenues for the development of analgesics. PMID- 26260772 TI - The effect of surgical timing on the outcome of patients with neck of femur fracture. AB - AIMS: To investigate the effect of surgical timing (in hours versus after hours and weekdays versus weekends) on the outcome of patients with neck of femur fracture. METHODS: Patients who were admitted to a single tertiary referral hospital for surgical management of femoral neck fractures over a continuous period from 1/11/2002 to 12/7/2012 were identified from medical records and the operating theatre database. RESULTS: A consecutive series of 2334 patients were included in the study. Of the patients who underwent surgery during the weekday and during usual hours, 18% (207/1135) experienced an adverse event, compared to 16% (193/1199) outside of these times. The difference between the two groups was not significant (p = 0.17). The same conclusion was made for the comparison between those who had surgery during the week with those who had surgery on the weekend (17%, 267/1546 and 17%, 133/788, respectively, p > 0.05). The proportion of patients who underwent surgery during hours that experienced an adverse event was significantly higher than those undergoing surgery out of hours (18%, 327/1789 and 13%, 73/545, respectively, p = 0.0081). When adjusted for age, ASA score and pre-operative stay, there was no statistical difference between those different sub-groups. CONCLUSIONS: There was no difference in the rates of adverse events between patients who had surgery during hours and weekdays with those who had surgery after hours or weekends. The careful selection of patients with appropriate hospital staff, resources and adequate theatre access, surgery during after hours and weekends may be safely considered to prevent a delay in surgical treatment for patient with neck of femur fracture. PMID- 26260773 TI - Resolving bundled microtubules using anti-tubulin nanobodies. AB - Microtubules are hollow biopolymers of 25-nm diameter and are key constituents of the cytoskeleton. In neurons, microtubules are organized differently between axons and dendrites, but their precise organization in different compartments is not completely understood. Super-resolution microscopy techniques can detect specific structures at an increased resolution, but the narrow spacing between neuronal microtubules poses challenges because most existing labelling strategies increase the effective microtubule diameter by 20-40 nm and will thereby blend neighbouring microtubules into one structure. Here we develop single-chain antibody fragments (nanobodies) against tubulin to achieve super-resolution imaging of microtubules with a decreased apparent diameter. To test the resolving power of these novel probes, we generate microtubule bundles with a known spacing of 50-70 nm and successfully resolve individual microtubules. Individual bundled microtubules can also be resolved in different mammalian cells, including hippocampal neurons, allowing novel insights into fundamental mechanisms of microtubule organization in cell- and neurobiology. PMID- 26260774 TI - The effects of laser repetition rate on femtosecond laser ablation of dry bone: a thermal and LIBS study. AB - The aim of this study is to understand the effect of varying laser repetition rate on thermal energy accumulation and dissipation as well as femtosecond Laser Induced Breakdown Spectroscopy (fsLIBS) signals, which may help create the framework for clinical translation of femtosecond lasers for surgical procedures. We study the effect of repetition rates on ablation widths, sample temperature, and LIBS signal of bone. SEM images were acquired to quantify the morphology of the ablated volume and fsLIBS was performed to characterize changes in signal intensity and background. We also report for the first time experimentally measured temperature distributions of bone irradiated with femtosecond lasers at repetition rates below and above carbonization conditions. While high repetition rates would allow for faster cutting, heat accumulation exceeds heat dissipation and results in carbonization of the sample. At repetition rates where carbonization occurs, the sample temperature increases to a level that is well above the threshold for irreversible cellular damage. These results highlight the importance of the need for careful selection of the repetition rate for a femtosecond laser surgery procedure to minimize the extent of thermal damage to surrounding tissues and prevent misclassification of tissue by fsLIBS analysis. PMID- 26260775 TI - The Brakeless co-regulator can directly activate and repress transcription in early Drosophila embryos. AB - The Brakeless protein performs many important functions during Drosophila development, but how it controls gene expression is poorly understood. We previously showed that Brakeless can function as a transcriptional co-repressor. In this work, we perform transcriptional profiling of brakeless mutant embryos. Unexpectedly, the majority of affected genes are down-regulated in brakeless mutants. We demonstrate that genomic regions in close proximity to some of these genes are occupied by Brakeless, that over-expression of Brakeless causes a reciprocal effect on expression of these genes, and that Brakeless remains an activator of the genes upon fusion to an activation domain. Together, our results show that Brakeless can both repress and activate gene expression. A yeast two hybrid screen identified the Mediator complex subunit Med19 as interacting with an evolutionarily conserved part of Brakeless. Both down- and up-regulated Brakeless target genes are also affected in Med19-depleted embryos, but only down regulated targets are influenced in embryos depleted of both Brakeless and Med19. Our data provide support for a Brakeless activator function that regulates transcription by interacting with Med19. We conclude that the transcriptional co regulator Brakeless can either activate or repress transcription depending on context. PMID- 26260776 TI - Prediction of response to preoperative chemoradiotherapy and establishment of individualized therapy in advanced rectal cancer. AB - Preoperative chemoradiotherapy (CRT) has become the standard treatment for patients with locally advanced rectal cancer. However, no specific biomarker has been identified to predict a response to preoperative CRT. The aim of the present study was to assess the gene expression patterns of patients with advanced rectal cancer to predict their responses to preoperative CRT. Fifty-nine rectal cancer patients were subjected to preoperative CRT. Patients were randomly assigned to receive CRT with tegafur/gimeracil/oteracil (S-1 group, n=30) or tegafur-uracil (UFT group, n=29). Gene expression changes were studied with cDNA and miRNA microarray. The association between gene expression and response to CRT was evaluated. cDNA microarray showed that 184 genes were significantly differentially expressed between the responders and the non-responders in the S-1 group. Comparatively, 193 genes were significantly differentially expressed in the responders in the UFT group. TBX18 upregulation was common to both groups whereas BTNL8, LOC375010, ADH1B, HRASLS2, LOC284232, GCNT3 and ALDH1A2 were significantly differentially lower in both groups when compared with the non responders. Using miRNA microarray, we found that 7 and 16 genes were significantly differentially expressed between the responders and non-responders in the S-1 and UFT groups, respectively. miR-223 was significantly higher in the responders in the S-1 group and tended to be higher in the responders in the UFT group. The present study identified several genes likely to be useful for establishing individualized therapies for patients with rectal cancer. PMID- 26260778 TI - Can biosemiotics be a "science" if its purpose is to be a bridge between the natural, social and human sciences? AB - Central to the attempt to develop a biosemiotics has been the discussion of what it means to be scientific. In Marcello Barbieri's latest argument for leaving Peircean biosemiotics and creating an alternative code-biology the definition of what it means to be scientific plays a major role. For Barbieri "scientific knowledge is obtained by building machine-like models of what we observe in nature". Barbieri interestingly claims that - in combination with the empirical and experimental basis - mechanism is virtually equivalent to the scientific method. The consequences of this statement seem to be that the optimal type of knowledge science can produce about living system is to model them as machines. But the explicit goal of a Peircean semiotically based biosemiotics is (also) to model living systems as cognitive and communicative systems working on the basis of meaning and signification. These two concepts are not part of the mechanistic models of natural science today, not even of cognitive science. Barbieri tries to solve this problem by introducing a new concept of biological meaning that is separate from the Peircean biosemiotics and then add Peirce's semiotics on top. This article argues why this view is inconsistent on the grounds that Peirce's semiotic paradigm only gives meaning in its pragmaticist conception of a fallibilist view of science, which again is intrinsic connected to its non mechanistic metaphysics of Tychism, Synechism and Agapism. The core of the biosemiotic enterprise is to establish another type of trans- and interdisciplinary wissenschaft than the received view of "science". PMID- 26260777 TI - A prospective analysis of diet quality and endometrial cancer among 84,415 postmenopausal women in the Women's Health Initiative. AB - PURPOSE: Endometrial cancer is the most commonly diagnosed gynecologic cancer, but no convincing dietary risk factors for this cancer have been identified. Among postmenopausal women, we examined how four key a priori diet quality indices--the Healthy Eating Index-2010, Alternative Healthy Eating Index-2010, alternate Mediterranean Diet, and Dietary Approaches to Stop Hypertension are related to the risk of endometrial cancer in the Women's Health Initiative Clinical Trials and Observational Study. METHODS: Our prospective cohort study included 84,415 postmenopausal women with a uterus who completed a food frequency questionnaire at enrollment. Cox proportional hazards models were used to estimate multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for endometrial cancer associated with increasing quintiles of diet quality index scores. RESULTS: During 13.3 years of follow-up, 1392 endometrial cancer cases occurred. After adjustment for known risk factors, having better diet quality (Q5 vs. Q1) was not associated with the risk of endometrial cancer, as evidenced using Healthy Eating Index-2010 (HR: 1.11, 95% CI: 0.93-1.33), Alternative Healthy Eating Index-2010 (HR: 0.98, 95% CI: 0.82-1.17), alternate Mediterranean Diet (HR: 0.98, 95% CI: 0.82-1.17), or Dietary Approaches to Stop Hypertension (HR: 1.00, 95% CI: 0.84-1.19). CONCLUSIONS: Diet quality was not associated with endometrial cancer risk in this large cohort of postmenopausal women. PMID- 26260779 TI - Semiosis stems from logical incompatibility in organic nature: Why biophysics does not see meaning, while biosemiotics does. AB - We suggest here a model of the origin of the phenomenal world via the naturalization of logical conflict or incompatibility (which is broader than, but includes logical contradiction). Physics rules out the reality of meaning because of the method of formalization, which requires that logical conflicts cannot be part of the model. We argue that (a) meaning-making requires a logical conflict; (b) logical conflict assumes a phenomenal present; (c) phenomenological specious present occurs in living systems as widely as meaning-making; (d) it is possible to provide a physiological description of a system in which the phenomenal present appears and choices are made; (e) logical conflict, or incompatibility itself, is the mechanism of intentionality; (f) meaning-making is assured by scaffolding, which is a product of earlier choices, or decision-making, or interpretation. This model can be seen as a model of semiosis. It also allows putting physiology and phenomenology (or physics and semiotics) into a natural connection. PMID- 26260780 TI - Rumination-focused cognitive behaviour therapy vs. cognitive behaviour therapy for depression: study protocol for a randomised controlled superiority trial. AB - BACKGROUND: Cognitive behavioural therapy is an effective treatment for depression. However, one third of the patients do not respond satisfactorily, and relapse rates of around 30 % within the first post-treatment year were reported in a recent meta-analysis. In total, 30-50 % of remitted patients present with residual symptoms by the end of treatment. A common residual symptom is rumination, a process of recurrent negative thinking and dwelling on negative affect. Rumination has been demonstrated as a major factor in vulnerability to depression, predicting the onset, severity, and duration of future depression. Rumination-focused cognitive behavioural therapy is a psychotherapeutic treatment targeting rumination. Because rumination plays a major role in the initiation and maintenance of depression, targeting rumination with rumination-focused cognitive behavioural therapy may be more effective in treating depression and reducing relapse than standard cognitive behavioural therapy. METHOD/DESIGN: This study is a two-arm pragmatic randomised controlled superiority trial comparing the effectiveness of group-based rumination-focused cognitive behaviour therapy with the effectiveness of group-based cognitive behavioural therapy for treatment of depression. One hundred twenty-eight patients with depression will be recruited from and given treatment in an outpatient service at a psychiatric hospital in Denmark. Our primary outcome will be severity of depressive symptoms (Hamilton Rating Scale for Depression) at completion of treatment. Secondary outcomes will be level of rumination, worry, anxiety, quality of life, behavioural activation, experimental measures of cognitive flexibility, and emotional attentional bias. A 6-month follow-up is planned and will include the primary outcome measure and assessment of relapse. DISCUSSION: The clinical outcome of this trial may guide clinicians to decide on the merits of including rumination-focused cognitive behavioural therapy in the treatment of depression in outpatient services. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02278224 , registered 28 Oct. 2014. PMID- 26260781 TI - Mutations of TSHR and TP53 Genes in an Aggressive Clear Cell Follicular Carcinoma of the Thyroid. AB - Clear cell follicular carcinoma is a rare type of thyroid cancer and some with aggressive biological behavior. The cytoplasmic clearing of the neoplastic cells has been attributed to the accumulation of various substances, such as glycogen, lipid, mucin, and thyroglobulin, or distension of mitochondria or endoplasmic reticulum. However, the molecular mechanisms responsible for the characteristic appearance of the cell cytoplasm and the biological behavior remain unknown. We report here a case of aggressive clear cell follicular carcinoma of the thyroid with molecular profile using targeted next generation sequencing (NGS) that presented as a metastatic tumor in a woman with a history of breast carcinoma. The NGS data revealed the coexisting of a well-characterized loss-of-function TP53 R248Q mutation and a putative gain-of-function mutation of TSHR L272V, which was suggested by the overexpression of thyroglobulin and SLC5A5 (NIS) genes in this tumor. TP53 mutations are usually related with dedifferentiation, progression, and metastasis of thyroid carcinomas. Identification of TP53 R248Q in this tumor correlated with its aggressive clinical behavior. Gain-of-function mutation of TSHR can overstimulate the thyroid follicular cells as the elevated level of TSH does and might have contributed to the development of clear cell morphology in this tumor. This report represents the first case of clear cell follicular carcinoma of the thyroid with NGS analysis and more molecular characterization is needed to elucidate the pathogenesis and provide more prognosis-relevant information for this uncommon variant of thyroid carcinomas. PMID- 26260782 TI - Computational modeling to predict nitrogen balance during acute metabolic decompensation in patients with urea cycle disorders. AB - Nutritional management of acute metabolic decompensation in amino acid inborn errors of metabolism (AA IEM) aims to restore nitrogen balance. While nutritional recommendations have been published, they have never been rigorously evaluated. Furthermore, despite these recommendations, there is a wide variation in the nutritional strategies employed amongst providers, particularly regarding the inclusion of parenteral lipids for protein-free caloric support. Since randomized clinical trials during acute metabolic decompensation are difficult and potentially dangerous, mathematical modeling of metabolism can serve as a surrogate for the preclinical evaluation of nutritional interventions aimed at restoring nitrogen balance during acute decompensation in AA IEM. A validated computational model of human macronutrient metabolism was adapted to predict nitrogen balance in response to various nutritional interventions in a simulated patient with a urea cycle disorder (UCD) during acute metabolic decompensation due to dietary non-adherence or infection. The nutritional interventions were constructed from published recommendations as well as clinical anecdotes. Overall, dextrose alone (DEX) was predicted to be better at restoring nitrogen balance and limiting nitrogen excretion during dietary non-adherence and infection scenarios, suggesting that the published recommended nutritional strategy involving dextrose and parenteral lipids (ISO) may be suboptimal. The implications for patients with AA IEM are that the medical course during acute metabolic decompensation may be influenced by the choice of protein-free caloric support. These results are also applicable to intensive care patients undergoing catabolism (postoperative phase or sepsis), where parenteral nutritional support aimed at restoring nitrogen balance may be more tailored regarding metabolic fuel selection. PMID- 26260783 TI - Stability of Uncemented Cups - Long-Term Effect of Screws, Pegs and HA Coating: A 14-Year RSA Follow-Up of Total Hip Arthroplasty. AB - Screws, pegs and hydroxyapatite-coating are used to enhance the primary stability of uncemented cups. We present a 14-year follow-up of 48 hips randomized to four groups: press-fit only, press-fit plus screws, press-fit plus pegs and hydroxyapatite-coated cups. Radiostereometric migration measurements showed equally good stability regardless cup augmentation. The mean wear rate was high, 0.21 mm/year, with no differences between the groups. Seven hips had radiographical osteolysis but only in hips with augmented cups. Cups without screw-holes compared with cups with screw-holes resulted in better clinical outcome at the 14-year follow-up. Thus, augmentation of uncemented cups with screws, pegs, or hydroxyapatite did not appear to improve the long-term stability compared with press-fit only. PMID- 26260784 TI - Teriparatide Versus Alendronate for the Preservation of Bone Mineral Density After Total Hip Arthroplasty - A randomized Controlled Trial. AB - In this study, the effect of teriparatide for the prevention of bone mineral density (BMD) loss after THA was compared with alendronate in a randomized controlled trial. Forty-eight patients were assigned to three groups, namely, the teriparatide, alendronate, and no medication groups. Dual-energy x-ray absorptiometry (DEXA) was performed at 1 week post-surgery as a baseline reference, followed by subsequent measurements at 12, 24, and 48 weeks postoperatively. For periprosthetic BMD loss, a significant effect of teriparatide was demonstrated, though its effect was similar to alendronate. On the other hand, higher lumbar BMD was observed in the teriparatide group than in the alendronate group at 48 weeks post-surgery. Teriparatide administration may be one reasonable option for osteoporotic patient to preserve the periprosthetic BMD after THA. PMID- 26260786 TI - Illness representations and psychological adjustment of Greek couples dealing with a recently-diagnosed cancer: dyadic, interaction and perception dissimilarity effects. AB - The aim was to examine the impact of the dyadic, interaction and dissimilarity effects of the illness representations on the psychological health of recently diagnosed cancer patients and spouses in Greece. The sample consisted of 298 individuals nested in 149 couples. Effects were examined with the Actor-Partner Interdependence Model. Both actor (i.e., within person) and partner (i.e., between partners) effects were detected for both patients' and spouses' psychological symptoms. The negative association of patients' psychological symptoms with their representations of illness coherence was weak at the higher and medium levels, and stronger at the lower levels of spouse corresponding representations. Patient-partner discrepancy in perceived illness consequences was associated with more psychological symptoms in patients. Adaptation to cancer is a dyadic process within the context of which patient and partner psychological well-being is affected by each other's understanding of illness. Thus, the parallel examination of the illness representations of both partners is needed from the early phases of the illness trajectory. PMID- 26260785 TI - Long-Term Results of Total Hip Arthroplasty with 28-Millimeter Cobalt-Chromium Femoral Heads on Highly Cross-Linked Polyethylene in Patients 50 Years and Less. AB - Highly cross-linked polyethylene (HXLPE) is the most commonly used bearing surface in total hip arthroplasty (THA) because of its superior wear properties, but long-term results in young patients are limited. We report on the clinical outcome, radiographic wear patterns and survivorship of 72 patients <=50 years old who had a 28-millimeter cobalt-chromium femoral head on HXLPE acetabular liner. Mean and median true linear wear rates at average ten-year follow-up were 0.0104 and 0.01 mm per year +/- 0.07 mm. Mean and median two-dimensional volumetric wear rates were 12.79 mm(3) and 5.834 mm(3) per year +/- 26.1mm(3) as determined by Martell analysis. As a result of the minimal wear profile, there was no evidence of radiographic osteolysis and no wear-related revisions. PMID- 26260787 TI - Coq6 is responsible for the C4-deamination reaction in coenzyme Q biosynthesis in Saccharomyces cerevisiae. AB - The yeast Saccharomyces cerevisiae is able to use para-aminobenzoic acid (pABA) in addition to 4-hydroxybenzoic acid as a precursor of coenzyme Q, a redox lipid essential to the function of the mitochondrial respiratory chain. The biosynthesis of coenzyme Q from pABA requires a deamination reaction at position C4 of the benzene ring to substitute the amino group with an hydroxyl group. We show here that the FAD-dependent monooxygenase Coq6, which is known to hydroxylate position C5, also deaminates position C4 in a reaction implicating molecular oxygen, as demonstrated with labeling experiments. We identify mutations in Coq6 that abrogate the C4-deamination activity, whereas preserving the C5-hydroxylation activity. Several results support that the deletion of Coq9 impacts Coq6, thus explaining the C4-deamination defect observed in Deltacoq9 cells. The vast majority of flavin monooxygenases catalyze hydroxylation reactions on a single position of their substrate. Coq6 is thus a rare example of a flavin monooxygenase that is able to act on two different carbon atoms of its C4-aminated substrate, allowing its deamination and ultimately its conversion into coenzyme Q by the other proteins constituting the coenzyme Q biosynthetic pathway. PMID- 26260788 TI - Heterologous expression of moss light-harvesting complex stress-related 1 (LHCSR1), the chlorophyll a-xanthophyll pigment-protein complex catalyzing non photochemical quenching, in Nicotiana sp. AB - Oxygenic photosynthetic organisms evolved mechanisms for thermal dissipation of energy absorbed in excess to prevent formation of reactive oxygen species. The major and fastest component, called non-photochemical quenching, occurs within the photosystem II antenna system by the action of two essential light-harvesting complex (LHC)-like proteins, photosystem II subunit S (PSBS) in plants and light harvesting complex stress-related (LHCSR) in green algae and diatoms. In the evolutionary intermediate Physcomitrella patens, a moss, both gene products are active. These proteins, which are present in low amounts, are difficult to purify, preventing structural and functional analysis. Here, we report on the overexpression of the LHCSR1 protein from P. patens in the heterologous systems Nicotiana benthamiana and Nicotiana tabacum using transient and stable nuclear transformation. We show that the protein accumulated in both heterologous systems is in its mature form, localizes in the chloroplast thylakoid membranes, and is correctly folded with chlorophyll a and xanthophylls but without chlorophyll b, an essential chromophore for plants and algal LHC proteins. Finally, we show that recombinant LHCSR1 is active in quenching in vivo, implying that the recombinant protein obtained is a good material for future structural and functional studies. PMID- 26260789 TI - Impact of Cell-surface Antigen Expression on Target Engagement and Function of an Epidermal Growth Factor Receptor * c-MET Bispecific Antibody. AB - The efficacy of engaging multiple drug targets using bispecific antibodies (BsAbs) is affected by the relative cell-surface protein levels of the respective targets. In this work, the receptor density values were correlated to the in vitro activity of a BsAb (JNJ-61186372) targeting epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (c-MET). Simultaneous binding of the BsAb to both receptors was confirmed in vitro. By using controlled Fab-arm exchange, a set of BsAbs targeting EGFR and c-MET was generated to establish an accurate receptor quantitation of a panel of lung and gastric cancer cell lines expressing heterogeneous levels of EGFR and c-MET. EGFR and c-MET receptor density levels were correlated to the respective gene expression levels as well as to the respective receptor phosphorylation inhibition values. We observed a bias in BsAb binding toward the more highly expressed of the two receptors, EGFR or c-MET, which resulted in the enhanced in vitro potency of JNJ 61186372 against the less highly expressed target. On the basis of these observations, we propose an avidity model of how JNJ-61186372 engages EGFR and c MET with potentially broad implications for bispecific drug efficacy and design. PMID- 26260790 TI - Adipose Tissue Lipolysis Promotes Exercise-induced Cardiac Hypertrophy Involving the Lipokine C16:1n7-Palmitoleate. AB - Endurance exercise training induces substantial adaptive cardiac modifications such as left ventricular hypertrophy (LVH). Simultaneously to the development of LVH, adipose tissue (AT) lipolysis becomes elevated upon endurance training to cope with enhanced energy demands. In this study, we investigated the impact of adipose tissue lipolysis on the development of exercise-induced cardiac hypertrophy. Mice deficient for adipose triglyceride lipase (Atgl) in AT (atATGL KO) were challenged with chronic treadmill running. Exercise-induced AT lipolytic activity was significantly reduced in atATGL-KO mice accompanied by the absence of a plasma fatty acid (FA) increase. These processes were directly associated with a prominent attenuation of myocardial FA uptake in atATGL-KO and a significant reduction of the cardiac hypertrophic response to exercise. FA serum profiling revealed palmitoleic acid (C16:1n7) as a new molecular co-mediator of exercise-induced cardiac hypertrophy by inducing nonproliferative cardiomyocyte growth. In parallel, serum FA analysis and echocardiography were performed in 25 endurance athletes. In consonance, the serum C16:1n7 palmitoleate level exhibited a significantly positive correlation with diastolic interventricular septum thickness in those athletes. No correlation existed between linoleic acid (18:2n6) and diastolic interventricular septum thickness. Collectively, our data provide the first evidence that adipose tissue lipolysis directly promotes the development of exercise-induced cardiac hypertrophy involving the lipokine C16:1n7 palmitoleate as a molecular co-mediator. The identification of a lipokine involved in physiological cardiac growth may help to develop future lipid-based therapies for pathological LVH or heart failure. PMID- 26260791 TI - ATP-binding cassette transporter A7 (ABCA7) loss of function alters Alzheimer amyloid processing. AB - The ATP-binding cassette transporter A7 (ABCA7) has been identified as a susceptibility factor of late onset Alzheimer disease in genome-wide association studies. ABCA7 has been shown to mediate phagocytosis and affect membrane trafficking. The current study examined the impact of ABCA7 loss of function on amyloid precursor protein (APP) processing and generation of amyloid-beta (Abeta). Suppression of endogenous ABCA7 in several different cell lines resulted in increased beta-secretase cleavage and elevated Abeta. ABCA7 knock-out mice displayed an increased production of endogenous murine amyloid Abeta42 species. Crossing ABCA7-deficient animals to an APP transgenic model resulted in significant increases in the soluble Abeta as compared with mice expressing normal levels of ABCA7. Only modest changes in the amount of insoluble Abeta and amyloid plaque densities were observed once the amyloid pathology was well developed, whereas Abeta deposition was enhanced in younger animals. In vitro studies indicated a more rapid endocytosis of APP in ABCA7 knock-out cells that is mechanistically consistent with the increased Abeta production. These in vitro and in vivo findings indicate a direct role of ABCA7 in amyloid processing that may be associated with its primary biological function to regulate endocytic pathways. Several potential loss-of-function ABCA7 mutations and deletions linked to Alzheimer disease that in some instances have a greater impact than apoE allelic variants have recently been identified. A reduction in ABCA7 expression or loss of function would be predicted to increase amyloid production and that may be a contributing factor in the associated Alzheimer disease susceptibility. PMID- 26260792 TI - Characterization of the Catalytic and Nucleotide Binding Properties of the alpha Kinase Domain of Dictyostelium Myosin-II Heavy Chain Kinase A. AB - The alpha-kinases are a widely expressed family of serine/threonine protein kinases that exhibit no sequence identity with conventional eukaryotic protein kinases. In this report, we provide new information on the catalytic properties of the alpha-kinase domain of Dictyostelium myosin-II heavy chain kinase-A (termed A-CAT). Crystallization of A-CAT in the presence of MgATP yielded structures with AMP or adenosine in the catalytic cleft together with a phosphorylated Asp-766 residue. The results show that the beta- and alpha phosphoryl groups are transferred either directly or indirectly to the catalytically essential Asp-766. Biochemical assays confirmed that A-CAT hydrolyzed ATP, ADP, and AMP with kcat values of 1.9, 0.6, and 0.32 min(-1), respectively, and showed that A-CAT can use ADP to phosphorylate peptides and proteins. Binding assays using fluorescent 2'/3'-O-(N-methylanthraniloyl) analogs of ATP and ADP yielded Kd values for ATP, ADP, AMP, and adenosine of 20 +/- 3, 60 +/- 20, 160 +/- 60, and 45 +/- 15 MUM, respectively. Site-directed mutagenesis showed that Glu-713, Leu-716, and Lys-645, all of which interact with the adenine base, were critical for nucleotide binding. Mutation of the highly conserved Gln 758, which chelates a nucleotide-associated Mg(2+) ion, eliminated catalytic activity, whereas loss of the highly conserved Lys-722 and Arg-592 decreased kcat values for kinase and ATPase activities by 3-6-fold. Mutation of Asp-663 impaired kinase activity to a much greater extent than ATPase, indicating a specific role in peptide substrate binding, whereas mutation of Gln-768 doubled ATPase activity, suggesting that it may act to exclude water from the active site. PMID- 26260793 TI - NEDD8 Ultimate Buster 1 Long (NUB1L) Protein Suppresses Atypical Neddylation and Promotes the Proteasomal Degradation of Misfolded Proteins. AB - Neddylation is a posttranslational modification that controls diverse biological processes by covalently conjugating the ubiquitin-like protein NEDD8 to specific targets. Neddylation is commonly mediated by NEDD8-specific enzymes (typical neddylation) and, sometimes, by ubiquitin enzymes (atypical neddylation). Although typical neddylation is known to regulate protein function in many ways, the regulatory mechanisms and biological consequence of atypical neddylation remain largely unexplored. Here we report that NEDD8 conjugates were accumulated in the diseased hearts from mouse models and human patients. Proteotoxic stresses induced typical and atypical neddylation in cardiomyocytes. Loss of NUB1L exaggerated atypical neddylation, whereas NUB1L overexpression repressed atypical neddylation through promoting the degradation of NEDD8. Activation of atypical neddylation accumulated a surrogate misfolded protein, GFPu. In contrast, suppression of atypical neddylation by NUB1L overexpression enhanced GFPu degradation. Moreover, NUB1L depletion accumulated a cardiomyopathy-linked misfolded protein, CryAB(R120G), whereas NUB1L overexpression promoted its degradation through suppressing neddylation of ubiquitinated proteins in cardiomyocytes. Consequently, NUB1L protected cells from proteotoxic stress induced cell injury. In summary, these data indicate that NUB1L suppresses atypical neddylation and promotes the degradation of misfolded proteins by the proteasome. Our findings also suggest that induction of NUB1L could potentially become a novel therapeutic strategy for diseases with increased proteotoxic stress. PMID- 26260794 TI - Site-specific Interaction Mapping of Phosphorylated Ubiquitin to Uncover Parkin Activation. AB - Damaged mitochondria are eliminated through autophagy machinery. A cytosolic E3 ubiquitin ligase Parkin, a gene product mutated in familial Parkinsonism, is essential for this pathway. Recent progress has revealed that phosphorylation of both Parkin and ubiquitin at Ser(65) by PINK1 are crucial for activation and recruitment of Parkin to the damaged mitochondria. However, the mechanism by which phosphorylated ubiquitin associates with and activates phosphorylated Parkin E3 ligase activity remains largely unknown. Here, we analyze interactions between phosphorylated forms of both Parkin and ubiquitin at a spatial resolution of the amino acid residue by site-specific photo-crosslinking. We reveal that the in-between-RING (IBR) domain along with RING1 domain of Parkin preferentially binds to ubiquitin in a phosphorylation-dependent manner. Furthermore, another approach, the Fluoppi (fluorescent-based technology detecting protein-protein interaction) assay, also showed that pathogenic mutations in these domains blocked interactions with phosphomimetic ubiquitin in mammalian cells. Molecular modeling based on the site-specific photo-crosslinking interaction map combined with mass spectrometry strongly suggests that a novel binding mechanism between Parkin and ubiquitin leads to a Parkin conformational change with subsequent activation of Parkin E3 ligase activity. PMID- 26260795 TI - Critical Role of the Neonatal Fc Receptor (FcRn) in the Pathogenic Action of Antimitochondrial Autoantibodies Synergizing with Anti-desmoglein Autoantibodies in Pemphigus Vulgaris. AB - Pemphigus vulgaris (PV) is a life-long, potentially fatal IgG autoantibody mediated blistering disease targeting mucocutaneous keratinocytes (KCs). PV patients develop pathogenic anti-desmoglein (Dsg) 3 +/- 1 and antimitochondrial antibodies (AMA), but it remained unknown whether and how AMA enter KCs and why other cell types are not affected in PV. Therefore, we sought to elucidate mechanisms of cell entry, trafficking, and pathogenic action of AMA in PV. We found that PVIgGs associated with neonatal Fc receptor (FcRn) on the cell membrane, and the PVIgG-FcRn complexes entered KCs and reached mitochondria where they dissociated. The liberated AMA altered mitochondrial membrane potential, respiration, and ATP production and induced cytochrome c release, although the lack or inactivation of FcRn abolished the ability of PVIgG to reach and damage mitochondria and to cause detachment of KCs. The assays of mitochondrial functions and keratinocyte adhesion demonstrated that although the pathobiological effects of AMA on KCs are reversible, they become irreversible, leading to epidermal blistering (acantholysis), when AMA synergize with anti-Dsg antibodies. Thus, it appears that AMA enter a keratinocyte in a complex with FcRn, become liberated from the endosome in the cytosol, and are trafficked to the mitochondria, wherein they trigger pro-apoptotic events leading to shrinkage of basal KCs uniquely expressing FcRn in epidermis. During recovery, KCs extend their cytoplasmic aprons toward neighboring cells, but anti-Dsg antibodies prevent assembly of nascent desmosomes due to steric hindrance, thus rendering acantholysis irreversible. In conclusion, FcRn is a common acceptor protein for internalization of AMA and, perhaps, for PV autoantibodies to other intracellular antigens, and PV is a novel disease paradigm for investigating and elucidating the role of FcRn in this autoimmune disease and possibly other autoimmune diseases. PMID- 26260796 TI - The role of high cholesterol-high fructose diet on coronary arteriosclerosis. AB - The effect of fructose in conjunction with high cholesterol diet in the development of atherosclerotic lesions in coronary arteries is not well established. Microswine were fed high cholesterol (HC) or a high cholesterol-high fructose (HCHF) diet containing 18-20% calories from fructose. All swine had high levels of serum cholesterol and non-HDL, thickened intima and accumulation of collagen in the coronaries. Swine fed with HC diet had less stenosis in coronary arteries, lower serum levels of non-HDL, triglycerides, cholesterol, and blood glucose than HCHF group. Coronary lesions in the HC swine were not as progressed as in HCHF and showed low LDL-expressed lipid-laden foam cells. The M1/M2 macrophage phenotype in the HCHF swine differed with the progression of atherosclerosis, with higher density of M1-phenotype in HCHF swine. There was high expression of CCR7 (M1-phenotype) in more advanced lesions in the fibrous cap-like areas, whereas M2-macrophages were abundant in the foam-cell cores. These findings suggest that the addition of a fructose to high cholesterol diet accelerates atherosclerotic lesions in coronary arteries with an increase in M1 macrophages and the propensity to develop features of metabolic syndrome. PMID- 26260797 TI - Superradiant Quantum Heat Engine. AB - Quantum physics revolutionized classical disciplines of mechanics, statistical physics, and electrodynamics. One branch of scientific knowledge however seems untouched: thermodynamics. Major motivation behind thermodynamics is to develop efficient heat engines. Technology has a trend to miniaturize engines, reaching to quantum regimes. Development of quantum heat engines (QHEs) requires emerging field of quantum thermodynamics. Studies of QHEs debate whether quantum coherence can be used as a resource. We explore an alternative where it can function as an effective catalyst. We propose a QHE which consists of a photon gas inside an optical cavity as the working fluid and quantum coherent atomic clusters as the fuel. Utilizing the superradiance, where a cluster can radiate quadratically faster than a single atom, we show that the work output becomes proportional to the square of the number of the atoms. In addition to practical value of cranking up QHE, our result is a fundamental difference of a quantum fuel from its classical counterpart. PMID- 26260798 TI - Matrix cross-linking lysyl oxidases are induced in response to myocardial infarction and promote cardiac dysfunction. AB - AIMS: After myocardial infarction (MI), extensive remodelling of the extracellular matrix contributes to scar formation. While aiming to preserve tissue integrity, this fibrotic response is also associated with adverse events, including a markedly increased risk of heart failure, ventricular arrhythmias, and sudden cardiac death. Cardiac fibrosis is characterized by extensive deposition of collagen and also by increased stiffness as a consequence of enhanced collagen cross-linking. Members of the lysyl oxidase (LOX) family of enzymes are responsible for the formation of collagen cross-links. This study investigates the contribution of LOX family members to the heart response to MI. METHODS AND RESULTS: Experimental MI was induced in C57BL/6 mice by permanent ligation of the left anterior descending coronary artery. The expression of LOX isoforms (LOX and LOXL1-4) was strongly increased upon MI, and this response was accompanied by a significant accumulation of mature collagen fibres in the infarcted area. LOX expression was observed in areas of extensive remodelling, partially overlapping with alpha-smooth muscle actin-expressing myofibroblasts. Tumour growth factor-beta as well as hypoxia-activated pathways contributed to the induction of LOX expression in cardiac fibroblasts. Finally, in vivo post infarction treatment with the broadband LOX inhibitor beta-aminopropionitrile or, selectively, with a neutralizing antibody against the canonical LOX isoform attenuated collagen accumulation and maturation and also resulted in reduced ventricular dilatation and improved cardiac function. CONCLUSION: LOX family members contribute significantly to the detrimental effects of cardiac remodelling, highlighting LOX inhibition as a potential therapeutic strategy for post-infarction recovery. PMID- 26260799 TI - Cardiac protein kinases: the cardiomyocyte kinome and differential kinase expression in human failing hearts. AB - AIMS: Protein kinases are potential therapeutic targets for heart failure, but most studies of cardiac protein kinases derive from other systems, an approach that fails to account for specific kinases expressed in the heart and the contractile cardiomyocytes. We aimed to define the cardiomyocyte kinome (i.e. the protein kinases expressed in cardiomyocytes) and identify kinases with altered expression in human failing hearts. METHODS AND RESULTS: Expression profiling (Affymetrix microarrays) detected >400 protein kinase mRNAs in rat neonatal ventricular myocytes (NVMs) and/or adult ventricular myocytes (AVMs), 32 and 93 of which were significantly up-regulated or down-regulated (greater than two fold), respectively, in AVMs. Data for AGC family members were validated by qPCR. Proteomics analysis identified >180 cardiomyocyte protein kinases, with high relative expression of mitogen-activated protein kinase cascades and other known cardiomyocyte kinases (e.g. CAMKs, cAMP-dependent protein kinase). Other kinases are poorly investigated (e.g. Slk, Stk24, Oxsr1). Expression of Akt1/2/3, BRaf, ERK1/2, Map2k1, Map3k8, Map4k4, MST1/3, p38-MAPK, PKCdelta, Pkn2, Ripk1/2, Tnni3k, and Zak was confirmed by immunoblotting. Relative to total protein, Map3k8 and Tnni3k were up-regulated in AVMs vs. NVMs. Microarray data for human hearts demonstrated variation in kinome expression that may influence responses to kinase inhibitor therapies. Furthermore, some kinases were up-regulated (e.g. NRK, JAK2, STK38L) or down-regulated (e.g. MAP2K1, IRAK1, STK40) in human failing hearts. CONCLUSION: This characterization of the spectrum of kinases expressed in cardiomyocytes and the heart (cardiomyocyte and cardiac kinomes) identified novel kinases, some of which are differentially expressed in failing human hearts and could serve as potential therapeutic targets. PMID- 26260801 TI - Treating operable patients with gastric cancer: Macdonald's protocol versus adjuvant chemotherapy. PMID- 26260800 TI - Discordant circulating fetal DNA and subsequent cytogenetics reveal false negative, placental mosaic, and fetal mosaic cfDNA genotypes. AB - BACKGROUND: The American College of Obstetrics and Gynecology (ACOG) and Maternal Fetal Medicine (MFM) Societies recommended that abnormal cfDNA fetal results should be confirmed by amniocentesis and karyotyping. Our results demonstrate that normal cfDNA results inconsistent with high-resolution abnormal ultrasounds should be confirmed by karyotyping following a substantial frequency of incorrect cfDNA results. METHODS: Historical review of our ~4,000 signed prenatal karyotypes found ~24% of reported abnormalities would not have been detected by cfDNA. Akron Children's Hospital Cytogenetics Laboratory has completed 28 abnormal cfDNA cases among the 112 amniocenteses karyotyped. RESULTS: Following abnormal cfDNA results our karyotypes confirmed only 60% of the cfDNA results were consistent. Our cases found a normal cfDNA test result followed by a 20 weeks anatomical ultrasound detected a false negative trisomy 18 cfDNA result. One cfDNA result that reported trisomy 21 in the fetus was confirmed by karyotyping which also added an originally undetected balanced reciprocal translocation. Another reported karyotyped case followed by a repeated microarray of pure fetal DNA, together revealed one phenotypically normal newborn with a complex mosaic karyotype substantially decreasing the newborn's eventual reproductive fitness. This second case establishes the importance of karyotyping the placenta and cord or peripheral blood when inconsistent or mosaic results are identified following an abnormal cfDNA result with a normal newborn phenotype without a prenatal karyotype. CONCLUSIONS: These Maternal Fetal Medicine referrals demonstrate that positive NIPT results identify an increased abnormal karyotypic frequency as well as a substantial proportion of discordant fetal results. Our results found: (1) a normal NIPT test result followed by a 20 week anatomical ultrasound detected a false negative trisomy 18 NIPT result, (2) a substantial proportion of abnormal NIPT tests identify chromosomal mosaicism that may or may not be confined to the placenta, (3) follow up karyotyping should be completed on the newborn placenta and peripheral blood when the amniocyte karyotype does not confirm the NIPT reported abnormality in order to identify ongoing risk of developing mosaic symptoms, and (4) karyotyping all high risk fetuses tested by amniocentesis defines the 24% of chromosome abnormalities not currently screened by NIPT. PMID- 26260802 TI - Everolimus-based therapy in patients with hormone receptor-positive, HER2(-) advanced breast cancer: management considerations. PMID- 26260803 TI - Present status and future perspectives of ALPPS (associating liver partition and portal vein ligation for staged hepatectomy). AB - First International Consensus Meeting, Hamburg, Germany, 27-28 February 2015 More than 160 participants took part in the conference for 2 days. A total of 58 world renown experts on ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) were invited from all over the world. The faculty was divided into many different subgroups that were in contact during the 2-3 months before the conference analyzing all the most important aspects of this technique and summarizing it in a common structured work to be presented during the congress, giving final recommendations in the form of bulleted point statements. The aim was to gain a solid basis of preliminary agreement on many controversial aspects of ALPPS. A poster area was also organized with 35 posters reporting mostly mono institutional experiences on single aspects of the technique from all five continents. PMID- 26260804 TI - Can cardio-oncology deliver better care internationally? PMID- 26260805 TI - Sorafenib: the gold standard therapy in advanced hepatocellular carcinoma and beyond. PMID- 26260806 TI - Feasibility, efficacy and safety of tyrosine kinase inhibitor treatment in hemodialyzed patients with renal cell cancer: 10 years of experience. AB - AIMS: Sine efficiency of tyrosine kinase inhibitor (TKI) therapy in dialyzed patients is still unclear we aim to analyze the outcome of treatment in such cohort. PATIENTS & METHODS: We analyzed treatment outcomes of patients with clear cell renal cell carcinoma (ccRCC) with special focus on those who were also treated with hemodialysis and described treatment safety and progression-free survival of eight patients treated with TKIs and hemodialysis. DISCUSSION & CONCLUSION: Our report supports statement that TKI treatment of dialyzed patients is safe and effective. ccRCC increases risk of developing renal insufficiency as well as end-stage renal disease that require dialysis. Introduction of multitargeted receptor kinase inhibitors (TKIs), including sunitinib, sorafenib and pazopanib significantly expanded life time expectancy of metastatic renal clear cell carcinoma. The advance also applies to patients with ccRCC and end stage renal disease who undergo dialyses. PMID- 26260807 TI - Coexpression of androgen receptor and FOXA1 in nonmetastatic triple-negative breast cancer: ancillary study from PACS08 trial. AB - AIM: Microarray studies identified a subgroup of molecular apocrine tumors (estrogen receptor [ER] negative/androgen receptor [AR] positive) that express luminal genes including FOXA1. FOXA1 may direct AR to sites normally occupied by ER in luminal tumors, inducing an estrogen-like gene program that stimulated proliferation. MATERIALS & METHODS: Expression of AR and FOXA1 was evaluated by immunohistochemistry in 592 patients with nonmetastatic triple-negative breast cancer (TNBC). RESULTS: Coexpression of AR and FOXA1 was found in 15.2% of patients. These tumors were more frequently lobular, found in older patients and exhibited a lower nuclear grade and a greater degree of node involvement. They less often exhibited lymphocytic infiltrate, pushing margins, syncytial architecture, central fibrosis or necrosis. CONCLUSION: TNBC with coexpression of AR and FOXA1 seems to behave like luminal tumors with a morphological profile distinct from other TNBC. These biomarkers could be useful to identify a subgroup of TNBC and could have future therapeutic implications. PMID- 26260808 TI - Anti-PD-1 and PD-L1 therapy for bladder cancer: what is on the horizon? AB - Oncologic therapeutics has evolved enormously as we entered the 21st century. Unfortunately, the treatment of advanced urothelial cancer has remained unchanged over the last two decades despite a better understanding of the genetic alterations in bladder cancer. Pathways such as the PI3K/AKT3/mTOR and FGFR have been implicated in urothelial bladder cancer. However, targeted therapies have not shown proven benefit yet and are still considered investigational. Recently, researchers have been successful in manipulating the systemic immune response to mount antitumor effects in melanoma, lung cancer and lymphoma. Historically, intravesical Bacillus Calmette-Guerin immunotherapy has been highly active in nonmuscle invasive bladder cancer. Early data suggest that immune checkpoint inhibitors will soon prove to be another cornerstone in the treatment armamentarium of advanced bladder cancer. PMID- 26260809 TI - Are predictions of cancer response to targeted drugs, based on effects in unrelated tissues, the 'Black Swan' events? AB - Adverse effects of targeted drugs on normal tissues can predict the cancer response. Rash correlates with efficacy of erlotinib, cetuximab and gefitinib and onset of arterial hypertension with response to bevacizumab, sunitinib, axitinib and sorafenib, possible examples of 'Black Swan' events, unexpected scientific observations, as described by Karl Popper in 1935. The proposition is that our patients have individual intrinsic variants of cell growth control, important for tumor response and adverse effects on tumor-unrelated tissue. This means that the lack of predictive side effects in healthy tissue is linked with poor results of tumor therapy when tumor resistance is caused by mechanisms that protect all cells of that patient from the targeted drug effects. PMID- 26260810 TI - The future of targeted therapies for brain metastases. AB - Brain metastases (BM) are an increasing challenge in the management of patients with advanced cancer. Treatment options for BM are limited and mainly focus on the application of local therapies. Systemic therapies including targeted therapies are only poorly investigated, as patients with BM were frequently excluded from clinical trials. Several targeted therapies have shown promising activity in patients with BM. In the present review we discuss existing and emerging targeted therapies for the most frequent BM primary tumor types. We focus on challenges in the conduction of clinical trials on targeted therapies in BM patients such as patient selection, combination with radiotherapy, the obstacles of the blood-brain barrier and the definition of study end points. PMID- 26260811 TI - Radiotherapy of non-small-cell lung cancer in the era of EGFR gene mutations and EGF receptor tyrosine kinase inhibitors. AB - Non-small-cell lung cancer (NSCLC) occurs, approximately, in 80-85% of all cases of lung cancer. The majority of patients present locally advanced or metastatic disease when diagnosed, with poor prognosis. The discovery of activating mutations in the EGFR gene has started a new era of personalized treatment for NSCLC patients. To improve the treatment outcome in patients with unresectable NSCLC and, in particular, EGFR mutated, a combined strategy of radiotherapy and medical treatment can be undertaken. In this review we will discuss preclinical data regarding EGF receptor (EGFR) tyrosine kinase inhibitors (TKIs) and radiotherapy, available clinical trials investigating efficacy and toxicity of combined treatment (thoracic or whole brain radiotherapy and EGFR-TKIs) and, also, the role of local radiation in mutated EGFR patients who developed EGFR-TKI resistance. PMID- 26260812 TI - The utility of molecular markers in pre-operative assessment of thyroid nodules. AB - The pre-operative diagnosis of thyroid tumors is determined by gold standard fine needle aspiration (FNA) biopsy. This has been widely accepted and offers the most cost-effective approach for evaluation of thyroid nodules. However, its diagnostic accuracy can pose a challenging scenario to surgeons. These diagnostic difficulties may subject patients to unnecessary thyroidectomies for benign thyroid nodules. Thus, additional molecular tests are needed to improve the sensitivity and specificity of FNA. The role of molecular markers is being proposed to predict the type and risk of malignancy to abate the need for diagnostic thyroidectomies. This review discusses their utility and validity in pre-operative diagnosis of thyroid nodules and how these markers can enhance the accuracy of FNA cytology. PMID- 26260813 TI - miRNA-15a/16: as tumor suppressors and more. AB - Since their first discovery in chronic lymphocytic leukemia, miR-15a and miR-16 have been reported to act as tumor suppressors or potential oncomiRs in different types of cancer. This review summarizes the history, biological properties and the important functions of these two miRNAs in cancer. It also introduces their roles as regulators of immune responses and angiogenesis, endogenous controls as well as potential targets and hallmarks of cancer. PMID- 26260814 TI - Lung function impairment in the never-smoker: the search for answers continues. PMID- 26260815 TI - Tuberculosis preventive chemotherapy: the times they are a-changin'. PMID- 26260816 TI - Clearing the smoke around the TB-HIV syndemic: smoking as a critical issue for TB and HIV treatment and care. AB - The collision of the tuberculosis (TB) and human immunodeficiency virus (HIV) epidemics has been described as a 'syndemic' due to the synergistic impact on the burden of both diseases. This paper explains the urgent need for practitioners and policy makers to address a third epidemic that exacerbates TB, HIV and TB HIV. Tobacco use is the leading cause of preventable death worldwide. Smoking is more prevalent among persons diagnosed with TB or HIV. Smoking is associated with tuberculous infection, TB disease and poorer anti-tuberculosis treatment outcomes. It is also associated with an increased risk of smoking-related diseases among people living with HIV, and smoking may also inhibit the effectiveness of life-saving ART. In this paper, we propose integrating into TB and HIV programmes evidence-based strategies from the 'MPOWER' package recommended by the World Health Organization's Framework Convention on Tobacco Control. Specific actions that can be readily incorporated into current practice are recommended to improve TB and HIV outcomes and care, and reduce the unnecessary burden of death and disease due to smoking. PMID- 26260817 TI - Population-wide preventive interventions for reducing the burden of chronic respiratory disease. AB - Chronic obstructive pulmonary disease and asthma impose a substantial burden of disease. This narrative review focuses on potential population-wide interventions that are likely to have an impact on these diseases. The developmental origins of adult disease commence in utero, with maternal nutrition being of particular interest. However, to date, trials of maternal allergen avoidance, dietary supplementation or probiotics have not shown consistent protective effects against asthma. Poor indoor air quality, especially from biomass fuels as well as second-hand tobacco smoke, is a well-recognised risk factor for chronic respiratory diseases. This can be modified by cleaner fuels, cooking stoves or heaters, and improved ventilation. Although allergens are a risk factor for childhood asthma, the results of interventions to reduce exposures have been disappointing. Traffic-related air pollution is associated with an increased incidence of asthma in children. Primary prevention of the adverse effects of air pollution has focused on the development of ambient air quality guidelines, but enforcement remains a challenge in many countries. Occupational asthma may be induced by sensitisers or irritants in the workplace. Prevention involves eliminating the agent or reducing exposure as far as possible, which is more effective than respiratory protective equipment. Smoking cessation remains a key proven preventive strategy for chronic respiratory diseases. There is now an international framework for tobacco control, and recent innovations include plain packaging of tobacco. Chronic respiratory diseases can be substantially prevented by the above population-wide interventions. PMID- 26260818 TI - Risk factors for lung function impairment among the general non-smoking Korean population. AB - SETTING: Nationwide general population in South Korea. OBJECTIVE: Except for tobacco smoking, risk factors for the impairment of lung function have not been widely evaluated. We evaluated the risk factors for lung function impairment among the general non-smoking Korean population. DESIGN: A total of 8164 non smokers from the spirometry data set of the Korean National Health and Nutrition Examination Surveys IV and V (2008-2010) were included in the study. After sex stratification, multiple survey logistic regression analyses were performed to estimate the association between potential risk factors and impaired lung function in this nationwide cross-sectional study. RESULTS: The proportion of non smokers among the general Korean population with forced expiratory volume in 1 s (FEV1) < 80% of predicted, forced vital capacity (FVC) < 80% of predicted and FEV1/FVC ratio < 0.7 were respectively 46.2%, 50.3% and 30.2%. In multiple survey logistic regression analyses, lung function impairment was associated with tuberculosis (TB) and asthma in female non-smokers and asthma in male non smokers. CONCLUSIONS: TB and asthma are risk factors for lung function impairment among Korean non-smokers. To prevent further lung function impairment, a careful control system for these factors should be considered when setting health policy priorities. PMID- 26260819 TI - Concomitant tuberculosis and lung cancer diagnosed by bronchoscopy. AB - SETTING: South Granada Health Area (SGHA), Spain. OBJECTIVE: To describe the characteristics of concomitant tuberculosis (TB) and lung cancer cases. DESIGN: A total of 319 TB cases diagnosed between January 2003 and December 2010 were evaluated and identified using a prospective database. During this period, samples of bronchial secretions were obtained from all patients who underwent fibreoptic bronchoscopy (FBS) as part of a TB screening programme. A descriptive study was conducted. RESULTS: Concomitant TB and lung cancer were diagnosed in 15 cases (4.7% of total TB cases). The most common radiographic finding was atelectasis (53.3%), and the most common histological type was epidermoid carcinoma (60%). Lung cancer stage was advanced (III-IV) in 60% of the cases. CONCLUSION: The association between TB and lung cancer found in the SGHA after implementing a TB screening programme was higher than in other studies. This suggests that it would be advisable to perform acid-fast bacilli smear and mycobacterial culture of bronchial aspirates in all patients with presumed lung cancer, particularly in high TB prevalence areas. PMID- 26260820 TI - Spatio-temporal analysis of tuberculous infection risk among clients of a homeless shelter during an outbreak. AB - SETTING: British Columbia (BC) has a low incidence of tuberculosis (TB), with the burden of endogenously acquired disease concentrated among vulnerable populations, including the homeless. In May 2008, a TB outbreak began in a BC homeless shelter, with a single index case seeding multiple secondary cases within the shelter. OBJECTIVE: To use nightly shelter records to quantify the risk of latent tuberculous infection (LTBI) among shelter clients as a function of their sleeping distance from and duration of exposure to the index case. DESIGN: Distance and duration of exposure were visualised and assessed using logistic regression with LTBI status as outcome. We used a novel machine learning approach to establish exposure thresholds that optimally separated infected and non-infected individuals. RESULTS: Of 161 exposed shelter clients, 58 had a recorded outcome of infected (n = 39) or non-infected (n = 19). Only duration of exposure to the index was associated with increased odds of infection (OR 1.26); stays of ? 5 nights put shelter clients at higher odds of infection (OR 4.97). CONCLUSION: The unique data set and analytical approach suggested that, in a shelter environment, long-term clients are at highest risk of LTBI and should be prioritised for screening during an outbreak investigation. PMID- 26260822 TI - Evaluation of the national tuberculosis surveillance program in Haiti. AB - OBJECTIVE: To assess the quality of tuberculosis (TB) surveillance in Haiti, including whether underreporting from facilities to the national level contributes to low national case registration. METHODS: We collected 2010 and 2012 TB case totals, reviewed laboratory registries, and abstracted individual TB case reports from 32 of 263 anti-tuberculosis treatment facilities randomly selected after stratification/weighting toward higher-volume facilities. We compared site results to national databases maintained by a non-governmental organization partner (International Child Care [ICC]) for 2010 and 2012, and the National TB Program (Programme National de Lutte contre la Tuberculose, PNLT) for 2012 only. RESULTS: Case registries were available at 30/32 facilities for 2010 and all 32 for 2012. Totals of 3711 (2010) and 4143 (2012) cases were reported at the facilities. Case totals per site were higher in site registries than in the national databases by 361 (9.7%) (ICC 2010), 28 (0.8%) (ICC 2012), and 31 (0.8%) cases (PNLT 2012). Of abstracted individual cases, respectively 11.8% and 6.8% were not recorded in national databases for 2010 (n = 323) and 2012 (n = 351). CONCLUSIONS: The evaluation demonstrated an improvement in reporting registered TB cases to the PNLT in Haiti between 2010 and 2012. Further improvement in case notification will require enhanced case detection and diagnosis. PMID- 26260823 TI - Correlates of default from anti-tuberculosis treatment: a case study using Kenya's electronic data system. AB - BACKGROUND: In 2012, the World Health Organization estimated that there were 120,000 new cases and 9500 deaths due to tuberculosis (TB) in Kenya. Almost a quarter of the cases were not detected, and the treatment of 4% of notified cases ended in default. OBJECTIVE: To identify the determinants of anti-tuberculosis treatment default. DESIGN: Data from 2012 and 2013 were retrieved from a national case-based electronic data recording system. A comparison was made between new pulmonary TB patients for whom treatment was interrupted vs. those who successfully completed treatment. RESULTS: A total of 106,824 cases were assessed. Human immunodeficiency virus infection was the single most influential risk factor for default (aOR 2.7). More than 94% of patients received family based directly observed treatment (DOT) and were more likely to default than patients who received DOT from health care workers (aOR 2.0). Caloric nutritional support was associated with lower default rates (aOR 0.89). Males were more likely to default than females (aOR 1.6). Patients cared for in the private sector were less likely to default than those in the public sector (aOR 0.86). CONCLUSION: Understanding the factors contributing to default can guide future program improvements and serve as a proxy to understanding the factors that constrain access to care among undetected cases. PMID- 26260825 TI - Investigating the quality of expectorated sputum for tuberculosis diagnosis in Bolivia. AB - A low-power microscope-based cytological system to assess the quality of expectorated sputum provided for tuberculosis (TB) diagnosis was piloted in Bolivia. A total of 3688 samples were subjected to visual and cytological examination in nine laboratories: of these, 591 (16%) were misclassified by visual examination and 294 (8%) were found to be degraded. The degree of discordance varied between locations, and laboratories received a higher number of degraded specimens from isolated health clinics. Cytological assessment of sputum was found to be feasible and identified areas for improvement in the Bolivian diagnostic system for TB. PMID- 26260824 TI - Feasibility of tuberculosis treatment monitoring by video directly observed therapy: a binational pilot study. AB - BACKGROUND: Although directly observed therapy (DOT) is recommended worldwide for monitoring anti-tuberculosis treatment, transportation and personnel requirements limit its use. OBJECTIVE: To evaluate the feasibility and acceptability of 'video DOT' (VDOT), which allows patients to record and transmit medication ingestion via videos watched remotely by health care providers to document adherence. METHODS: We conducted a single-arm trial among tuberculosis (TB) patients in San Diego, California, USA, (n = 43) and Tijuana, Mexico (n = 9) to represent high- and low-resource settings. Pre-/post-treatment interviews assessed participant characteristics and experiences. Adherence was defined as the proportion of observed doses to expected doses. RESULTS: The mean age was 37 years (range 18 86), 50% were male, and 88% were non-Caucasian. The mean duration of VDOT use was 5.5 months (range 1-11). Adherence was similar in San Diego (93%) and Tijuana (96%). Compared to time on in-person DOT, 92% preferred VDOT, 81% thought VDOT was more confidential, 89% never/rarely had problems recording videos, and 100% would recommend VDOT to others. Seven (13%) participants were returned to in person DOT and six (12%) additional participants had their phones lost, broken or stolen. CONCLUSIONS: VDOT was feasible and acceptable, with high adherence in both high- and low-resource settings. Efficacy and cost-effectiveness studies are needed. PMID- 26260826 TI - Evaluation of mobile digital light-emitting diode fluorescence microscopy in Hanoi, Viet Nam. AB - SETTING: Hanoi Lung Hospital, Hanoi, Viet Nam. OBJECTIVE: To compare the accuracy of CellScopeTB, a manually operated mobile digital fluorescence microscope, with conventional microscopy techniques. DESIGN: Patients referred for sputum smear microscopy to the Hanoi Lung Hospital from May to September 2013 were included. Ziehl-Neelsen (ZN) smear microscopy, conventional light-emitting diode (LED) fluorescence microscopy (FM), CellScopeTB-based LED FM and Xpert((r)) MTB/RIF were performed on sputum samples. The sensitivity and specificity of microscopy techniques were determined in reference to Xpert results, and differences were compared using McNemar's paired test of proportions. RESULTS: Of 326 patients enrolled, 93 (28.5%) were Xpert-positive for TB. The sensitivity of ZN microscopy, conventional LED FM, and CellScopeTB-based LED FM was respectively 37.6% (95%CI 27.8-48.3), 41.9% (95%CI 31.8-52.6), and 35.5% (95%CI 25.8-46.1). The sensitivity of CellScopeTB was similar to that of conventional LED FM (difference -6.5%, 95%CI -18.2 to 5.3, P = 0.33) and ZN microscopy (difference 2.2%, 95%CI -9.2 to 4.9, P = 0.73). The specificity was >99% for all three techniques. DISCUSSION: CellScopeTB performed similarly to conventional microscopy techniques in the hands of experienced TB microscopists. However, the sensitivity of all sputum microscopy techniques was low. Options enabled by digital microscopy, such as automated imaging with real-time computerized analysis, should be explored to increase sensitivity. PMID- 26260821 TI - Three months of weekly rifapentine plus isoniazid is less hepatotoxic than nine months of daily isoniazid for LTBI. AB - SETTING: Nine months of daily isoniazid (9H) and 3 months of once-weekly rifapentine plus isoniazid (3HP) are recommended treatments for latent tuberculous infection (LTBI). The risk profile for 3HP and the contribution of hepatitis C virus (HCV) infection to hepatotoxicity are unclear. OBJECTIVES: To evaluate the hepatotoxicity risk associated with 3HP compared to 9H, and factors associated with hepatotoxicity. DESIGN: Hepatotoxicity was defined as aspartate aminotransferase (AST) >3 times the upper limit of normal (ULN) with symptoms (nausea, vomiting, jaundice, or fatigue), or AST >5 x ULN. We analyzed risk factors among adults who took at least 1 dose of their assigned treatment. A nested case-control study assessed the role of HCV. RESULTS: Of 6862 participants, 77 (1.1%) developed hepatotoxicity; 52 (0.8%) were symptomatic; 1.8% (61/3317) were on 9H and 0.4% (15/3545) were on 3HP (P < 0.0001). Risk factors for hepatotoxicity were age, female sex, white race, non-Hispanic ethnicity, decreased body mass index, elevated baseline AST, and 9H. In the case control study, HCV infection was associated with hepatotoxicity when controlling for other factors. CONCLUSION: The risk of hepatotoxicity during LTBI treatment with 3HP was lower than the risk with 9H. HCV and elevated baseline AST were risk factors for hepatotoxicity. For persons with these risk factors, 3HP may be preferred. PMID- 26260827 TI - False-negative BD MGITTM TBc Identification Test results in routine tuberculosis diagnosis: a New Zealand perspective. AB - >We previously reported on a comparison of the AccuProbe((r)) Gen-Probe((r)) MTBC assay (AccuProbe) (BioMerieux, Marcy L'Etoile, France) with the Becton Dickinson (BD) MGITTM TBc Identification (TBc) Test (BD, Franklin Lakes, NJ, USA) in our laboratory. In the period following the shift from the AccuProbe assay to the TBc test, we obtained six false-negative results. On sequencing the mpt64 gene, we found that these false-negative cases had mutations in the mpt64 gene due to deletion, insertion or substitution. Despite the occurrence of false-negative results, we found that the reduced cost and minimal technical expertise, combined with a new testing algorithm, still make this test the preferred option for rapidly identifying Mycobacterium tuberculosis complex in MGIT cultures in a low TB burden country such as New Zealand. PMID- 26260828 TI - Auditing smear microscopy results according to time to detection using the BACTECTM MGITTM TB system. AB - Smear microscopy is a rapid method for the identification of the most infectious patients with mycobacterial infection. Suboptimal smear microscopy may significantly compromise or delay patient isolation and contact tracing. A stringent method for auditing mycobacterial smear results is thus needed. This article proposes an auditing tool based on time to detection (TTD) of culture positive samples using the automated BACTECTM MGITTM 960 TB system. In our study, sputum samples subjected to liquefaction and concentration before staining with a TTD of <= 13 days using the BACTEC system should be positive on smear microscopy. PMID- 26260829 TI - Routine use of Xpert(r) MTB/RIF in areas with different prevalences of HIV and drug-resistant tuberculosis. AB - SETTING: Despite the widespread introduction of Xpert((r)) MTB/RIF in developing countries, reports of its use and value in routine conditions remain limited. OBJECTIVE: To describe Xpert results in relation to microscopy, treatment initiation, cost and workload under routine conditions at four sites in Cambodia, Georgia, Kenya and Swaziland. DESIGN: Laboratory and clinical information on presumed TB patients were obtained from routine registers over a period of at least 6 months between March and November 2012. RESULTS: Among the 6086 presumed TB patients included in the analysis, Xpert testing increased the number of biologically confirmed cases by 15% to 67% compared to microscopy. Up to 12% of the initial Xpert results were inconclusive. Between 56% and 83% of patients were started on treatment based on microscopy and/or Xpert results, with median delays of 1-16 days. Rifampicin resistance was detected in 3-19% of Xpert-positive patients. CONCLUSION: Despite the additional numbers of cases detected by Xpert compared to microscopy, large proportions of patients are still started on treatment empirically in routine practice. Patient and specimen flow should be optimised to reduce delays in treatment initiation. Simple, non-sputum-based point-of-care tests with high sensitivity are needed to improve TB diagnosis and management. PMID- 26260830 TI - Impact of point-of-care implementation of Xpert(r) MTB/RIF: product vs. process innovation. AB - BACKGROUND: Both product innovation (e.g., more sensitive tests) and process innovation (e.g., a point-of-care [POC] testing programme) could improve patient outcomes. OBJECTIVE: To study the respective contributions of product and process innovation in improving patient outcomes. DESIGN: We implemented a POC programme using Xpert((r)) MTB/RIF in an out-patient clinic of a tertiary care hospital in India. We measured the impact of process innovation by comparing time to diagnosis with routine testing vs. POC testing. We measured the impact of product innovation by comparing accuracy and time to diagnosis using smear microscopy vs. POC Xpert. RESULTS: We enrolled 1012 patients over a 15-month period. Xpert had high accuracy, but the incremental value of one Xpert over two smears was only 6% (95%CI 3-12). Implementing Xpert as a routine laboratory test did not reduce the time to diagnosis compared to smear-based diagnosis. In contrast, the POC programme reduced the time to diagnosis by 5.5 days (95%CI 4.3-6.7), but required dedicated staff and substantial adaptation of clinic workflow. CONCLUSION: Process innovation by way of a POC Xpert programme had a greater impact on time to diagnosis than the product per se, and can yield important improvements in patient care that are complementary to those achieved by introducing innovative technologies. PMID- 26260831 TI - Contribution of Xpert(r) MTB/RIF to the diagnosis of pulmonary tuberculosis among TB-exposed children in The Gambia. AB - SETTING: Greater Banjul Area, The Gambia. OBJECTIVE: To conduct a pragmatic evaluation of the Xpert((r)) MTB/RIF assay in the diagnosis of tuberculosis (TB) among child contacts. DESIGN: In this prospective study, one induced sputum sample was obtained from TB contacts aged <15 years and tested using fluorescent microscopy, culture and Xpert. The diagnostic accuracy of the microbiological tests was evaluated against culture and 'all TB diagnosis and treatment' as separate reference standards. RESULTS: Using culture as a reference standard, Xpert was positive for Mycobacterium tuberculosis in 6/14 culture-positive and 6/473 culture-negative children, giving a sensitivity and specificity of respectively 42.9% (95%CI 17.7-71.1) and 98.7% (95%CI 97.2-99.5). With 'all TB diagnosis and treatment' as a composite reference standard, combined Xpert and culture tests were positive for M. tuberculosis in 20/62 children with TB disease (32.3%, 95%CI 20.9-45.3), which was comparable to the yield from microscopy, culture and Xpert combined (33.9%, 95%CI 22.3-47.0), but significantly higher than individual yields from each test. CONCLUSION: The sensitivity of Xpert is low in actively traced child contacts, but a combination of Xpert and mycobacterial culture has incremental benefits for the bacteriological confirmation of TB disease. PMID- 26260832 TI - Tuberculosis is frequently diagnosed within 12 months of diabetes mellitus. AB - BACKGROUND: Evidence regarding the effects of tuberculosis (TB) screening among patients with diabetes mellitus (DM) in intermediate TB burden countries is insufficient, and the most appropriate time point for TB screening is unclear. OBJECTIVE: To investigate trends in TB incidence among newly diagnosed DM patients. DESIGN: A retrospective cohort study of the claims database of the Health Insurance Review and Assessment Service in Korea was performed. Participants were newly diagnosed with type 2 DM in 2009. The study outcome was TB incidence between 2009 and 2011 among participants according to duration of type 2 DM. RESULTS: A cohort of 331,601 patients with newly diagnosed type 2 DM in 2009 was identified. During the 3-year follow-up period, 1533 patients were diagnosed with TB. The estimated incidence of TB among newly diagnosed type 2 DM patients was 18/10,000 patient-years (py) (95%CI 17.5-19.4). TB incidence was 33/10,000 py (95%CI 30.0-35.6) in the first 6 months, and 19/10,000 py (95%CI 16.5-20.6) in the following 6-month period. CONCLUSIONS: The risk of developing TB was increased among DM patients, particularly during the first 12 months after DM diagnosis. PMID- 26260833 TI - Conventional and real-time PCR targeting 16S ribosomal RNA for the detection of Mycobacterium tuberculosis complex. AB - SETTING: Conventional diagnostic methods for tuberculosis (TB) have limited sensitivity and specificity or are time-consuming. OBJECTIVE: 16S rDNA and 16S rRNA of Mycobacterium tuberculosis complex (MTC) were used as targets to develop sensitive and specific polymerase chain reactions (PCRs) to improve the diagnosis of MTC. DESIGN: We developed conventional and real-time PCRs targeting 16S rDNA and rRNA of MTC. RESULTS: PCRs targeting 16S rRNA had a 10-100 times lower limit of detection for M. tuberculosis than PCRs targeting 16S rDNA. The sensitivities of the 16S rDNA PCR, 16S rRNA reverse transcription PCR (RT-PCR), 16S rDNA real time PCR and 16S rRNA real-time RT-PCR for sputum specimens were respectively 92%, 94.6%, 96% and 100%. Real-time PCR showed no cross-reactivity, but conventional PCR had cross-reactivity to M. avium, M. gastri and M. nonchromogenicum. CONCLUSION: PCRs targeting the 16S rRNA of MTC were more sensitive than those targeting 16S rDNA; 16S rRNA real-time RT-PCR showed the highest sensitivity and specificity for MTC. PMID- 26260834 TI - Management and treatment outcomes of MDR-TB: results from a setting with high rates of drug resistance. AB - SETTINGS: Although Pakistan has a high burden of multidrug-resistant tuberculosis (MDR-TB), little is known about the management and treatment outcomes of MDR-TB patients in Pakistan. OBJECTIVE: To evaluate management and predictors of unsuccessful treatment outcomes among MDR-TB patients. METHODS: In this observational cohort study, 196 MDR-TB patients enrolled at the Programmatic Management Unit for drug-resistant TB of Lady Reading Hospital, Peshawar, Pakistan, between 1 January 2012 and 28 February 2013 were included. Patients were followed until an outcome was recorded or 31 January 2015. RESULTS: Extensive concurrent resistance to ofloxacin (OFX) and pyrazinamide (54.6%) was observed. Among 181 patients for whom treatment outcome was available, 135 (74.6%) were cured, 1 (0.6%) completed treatment, 35 (19.3%) died, 8 (4.4%) failed treatment and 2 (1.1%) defaulted. In multivariate analysis, predictors of unsuccessful treatment outcome (death, failure and default) were age >40 years (OR 3.412, P = 0.009), baseline body weight <40 kg (OR 2.966, P = 0.020), concurrent comorbidity (OR 3.785, P = 0.023), resistance to OFX (OR 2.777, P = 0.023), lung cavitations at baseline chest X-ray (OR 5.253, P < 0.001) and regimen modification due to adverse events (OR 3.492, P = 0.037). CONCLUSION: The treatment outcome results were encouraging. Patients with identifiable predictors of poor treatment outcome should receive enhanced clinical management. Early detection and management of mild adverse effects can help prevent regimen modification and may improve treatment outcomes. PMID- 26260835 TI - Cost-effectiveness of improvements in diagnosis and treatment accessibility for tuberculosis control in India. AB - SETTING: Inaccurate diagnosis and inaccessibility of care undercut the effectiveness of high-quality anti-tuberculosis treatment and select for resistance. Rapid diagnostic systems, such as Xpert((r)) MTB/RIF for tuberculosis (TB) diagnosis and drug susceptibility testing (DST), and programs that provide high-quality DOTS anti-tuberculosis treatment to patients in the unregulated private sector (public-private mix [PPM]), may help address these challenges, albeit at increased cost. OBJECTIVE/DESIGN: We extended a microsimulation model of TB in India calibrated to demographic, epidemiologic, and care trends to evaluate 1) replacing DST with Xpert; 2) replacing microscopy and culture with Xpert to diagnose multidrug-resistant TB (MDR-TB) and non-MDR-TB; 3) implementing nationwide PPM; and combinations of (3) with (1) or (2). RESULTS: PPM (assuming costs of $38/person) and Xpert improved health and increase costs relative to the status quo. PPM alone or with Xpert cost <1 gross domestic product/capita per quality-adjusted life-year gained relative to the next best intervention, and dominated Xpert interventions excluding PPM. CONCLUSIONS: While both PPM and Xpert are promising tools for combatting TB in India, PPM should be prioritized over Xpert, as private sector engagement is more cost-effective than Xpert alone and, if sufficient resources are available, would substantially increase the value of Xpert if both interventions are implemented together. PMID- 26260836 TI - Pott's disease in twenty-first century London: spinal tuberculosis as a continuing cause of morbidity and mortality. PMID- 26260837 TI - Notification of multidrug-resistant tuberculosis cases and treatment outcomes in the private sector. PMID- 26260838 TI - Bulk intermixing-type perovskite CH3NH3PbI3/TiO2 nanorod hybrid solar cells. AB - To replace high-temperature sintered scaffold materials in conventional CH3NH3PbI3-based solar cells, this study demonstrates a new device structure of a bulk intermixing (BI)-type CH3NH3PbI3/TiO2 nanorod (NR) hybrid solar cell, where dispersed TiO2 NRs from chemical synthesis are intermixed with the perovskite absorbing layer to form a BI-type perovskite/TiO2 NR hybrid for device fabrication. Through interface engineering between the TiO2 NR surface and the photoactive perovskite material of CH3NH3PbI3 by ligand exchange treatment, a remarkable power conversion efficiency (PCE) of over 12% was achieved based on the simple BI-type CH3NH3PbI3/TiO2 NR hybrid device structure. The proposed hybrids not only provide great flexibility for deposition on various substrates through spin coating at low temperatures but also enable layer-by-layer deposition for the future development of perovskite-based multi-junction solar cells. PMID- 26260839 TI - Isolation of a diphenylamine-degrading bacterium and characterization of its metabolic capacities, bioremediation and bioaugmentation potential. AB - The antioxidant diphenylamine (DPA) is used in fruit-packaging plants for the control of the physiological disorder apple scald. Its use results in the production of DPA-contaminated wastewater which should be treated before finally discharged. Biological treatment systems using tailored-made microbial inocula with specific catabolic activities comprise an appealing and sustainable solution. This study aimed to isolate DPA-degrading bacteria, identify the metabolic pathway of DPA and evaluate their potential for future implementation in bioremediation and biodepuration applications. A Pseudomonas putida strain named DPA1 able to rapidly degrade and utilize DPA as the sole C and N source was enriched from a DPA-contaminated soil. The isolated strain degraded spillage level concentrations of DPA in liquid culture (2000 mg L(-1)) and in contaminated soil (1000 mg kg(-1)) and metabolized DPA via the transient formation of aniline and catechol. Further evidence for the bioremediation and biodepuration potential of the P. putida strain DPA1 was provided by its capacity to degrade the post harvest fungicide ortho-phenylphenol (OPP), concurrently used by the fruit packaging plants, although at slower rates and DPA in a wide range of pH (4.5-9) and temperatures (15-37 degrees C). These findings revealed the high potential of the P. putida strain DPA1 for use in future soil bioremediation strategies and/or as start-up inocula in wastewater biodepuration systems. PMID- 26260840 TI - Do soil Fe transformation and secretion of low-molecular-weight organic acids affect the availability of Cd to rice? AB - The bioavailability of cadmium (Cd) to rice may be complicated by chemical and biological factors in the rhizosphere. The aim of this work is to investigate how soil iron (Fe) redox transformations and low-molecular-weight organic acid (LMWOA) exudation from root affect Cd accumulation in rice. Two soils (a paddy soil and a saline soil) with different physicochemical properties were used in this study. Soil redox conditions were changed by flooding and addition of organic matter (OM). Two days after the soil treatments, rice seedlings were transplanted in a vermiculite-soil system and grown for 10 days. We measured pH and Eh, LMWOA, Fe and Cd contents in rice, and their fractions in the soils and vermiculite. Cadmium accumulation in rice declined in both soils upon the flooding and OM treatment. Iron dissolution in the paddy soil and its deposition in the rhizosphere significantly increased upon the OM addition, but the concentration of Fe plaque on the rice root significantly declined. Conversely, although Fe transformed into less active fractions in the saline soil, Fe accumulation on the surface and in the tissue of root was considerably enhanced. The secretion of LMWOA was remarkably induced when the OM was amended in the saline soil, but the same effect was not observed in the paddy soil. Reduction of Cd uptake by rice could be attributed to different factors in the two soils. For the paddy soil, the lowered Cd bioavailability was likely due to the competition of Fe and Cd for the binding sites on the vermiculite surface. For the saline soil, however, rice responded to the low Fe mobility through more LMWOA exudation and Fe plaque formation, and their increases could explain the decrease of rice Cd. PMID- 26260841 TI - Magnetic nanoparticles with hydrophobicity and hydrophilicity for solid-phase extraction of polycyclic aromatic hydrocarbons from environmental water samples. AB - Magnetic nanoparticles (MNPs) featured with divinylbenzene (DVB) and sulfonate functionalities (Fe3O4-DVB-SO3(-)) were prepared via "thiol-ene" click chemistry. The hydrophobic DVB moieties were dedicated for extraction while the hydrophilic sulfonate groups were designed for dispersing the MNPs in aqueous sample solution. Thus, the specially designed material could ensure operational convenience and improve reproducibility during extraction. The application of the material was demonstrated by the extraction of polycyclic aromatic hydrocarbons (PAHs) from environmental water samples followed by gas chromatography-mass spectrometric analysis. The main factors influencing the extraction, including the type of the desorption solvent, the agitation mode, the amount of MNPs, extraction and desorption time and salt addition in sample solution, were investigated in detail. Under the optimized conditions, the proposed method showed satisfactory reproducibility with intra-day and inter-day relative standard deviations less than 16.5% and 21.2%, and low limits of detection of 1.1pgmL(-1), 0.8pgmL(-1), 1.1pgmL(-1), 1.4pgmL(-1), 0.6pgmL(-1), 2.1pgmL(-1) and 0.7pgmL(-1) for naphthalene, acenaphthene, fluorine, phenanthrene, anthracene, fluoranthene and pyrene, respectively. The developed method was also successfully used for determination of the PAHs in genuine lake and river environmental water samples by standard addition method. All the studied PAHs were detected in these waters with comparable results by the standard liquid-liquid extraction method. The developed MNPs with dual property of hydrophobicity and hydrophilicity were suitable for the treatment of water samples. The magnetic solid phase extraction based on this material was reliable and convenient. It has great potential in the preconcentration of trace analytes in complex matrix. PMID- 26260842 TI - Instrument platforms for thin-layer chromatography. AB - High performance column and thin-layer chromatography are both instrumental techniques but differ in that column chromatography requires a fully integrated instrument platform with high pressure capability while for thin-layer chromatography separate devices are used for each unit operation, usually at or close to atmospheric pressure, and afford higher flexibility supporting on-line or off-line operation. The unit operations of thin-layer chromatography are defined as sample application, development and evaluation with derivatization as an optional step. The diversity of equipment for each operation contributes to the flexibility of analysis by thin-layer chromatography and supports manual, semi-automated or full-automation of the separation process. Instrument platforms are more than a convenience as they affect performance, repeatability, sample detectability, and time management. The current trend in thin-layer chromatography is to make the unit operations independent of the user so that analysts can perform other tasks while each step is performed. In addition, in thin-layer chromatography it is general practice to separate several samples simultaneously, and instrument platforms are required to accommodate this feature. In this article, we review contemporary instrumentation employed in thin layer chromatography for sample application, development, derivatization, photodocumentation, densitometric evaluation, and hyphenation with spectroscopic detectors with an emphasis on the variety and performance of commercially available systems. Some suggestions for best practices and avoidance of common mistakes are included. PMID- 26260843 TI - Multigene synergism increases the isoflavone and proanthocyanidin contents of Medicago truncatula. AB - Isoflavones and proanthocyanidins (PAs), which are flavonoid derivatives, possess many health benefits and play important roles in forage-based livestock production. However, the foliage of Medicago species accumulates limited levels of both isoflavones and PAs. In this study, biosynthesis of isoflavone and PA in Medicago truncatula was enhanced via synergy between soya bean isoflavone synthase (IFS1); two upstream enzymes, chalcone synthase (CHS) and chalcone isomerase (CHI); and the endogenous flavanone 3-hydroxylase (F3H). Constitutive expression of GmIFS1 alone resulted in ectopic accumulation of the isoflavone daidzein and large increases in the levels of the isoflavones formononetin, genistein and biochanin A in the leaves. Furthermore, coexpression of GmIFS1 with GmCHS7 and GmCHI1A generally increased the available flux to flavonoid biosynthesis and resulted in elevated isoflavone, flavone and PA contents. In addition, down-regulation of MtF3H combined with coexpression of GmIFS1, GmCHS7 and GmCHI1A led to the highest isoflavone levels (up to 2 MUmol/g fresh weight in total). Taken together, our results demonstrate that multigene synergism is a powerful means to enhance the biosynthesis of particular flavonoids and can be more broadly applied to the metabolic engineering of forage species. PMID- 26260845 TI - NFkappaB- and AP-1-mediated DNA looping regulates matrix metalloproteinase-9 transcription in TNF-alpha-treated human leukemia U937 cells. AB - The aim of this study is to explore the spatial association of critical genomic elements in the effect of TNF-alpha on matrix metalloproteinase-9 (MMP-9) expression in human leukemia U937 cells. TNF-alpha up-regulated MMP-9 protein expression and mRNA level in U937 cells, and Akt-mediated-NFkappaB/p65 activation and JNK-mediated c-Jun activation were proven to be involved in TNF-alpha-induced MMP-9 up-regulation. Promoter luciferase activity assay revealed that NFkappaB (nt-600) and AP-1 (nt-79) binding sites were crucial for TNF-alpha-induced transcription of MMP-9 gene. The results of a chromatin immunoprecipitation assay indicated that TNF-alpha reduced histone deacetylase-1 (HDAC-1) recruitment but increased p300 (a histone acetyltransferase) recruitment to MMP-9 promoter regions surrounding NFkappaB and AP-1 binding sites. Consistently, TNF-alpha increased enrichment of the acetylated histone H3 mark on MMP-9 promoter regions. DNA affinity purification assay revealed that p300 and HDAC1 could bind oligonucleotides containing AP-1/c-Jun and NFkappaB/p65 binding sites. Chromosome conformation capture assay showed that TNF-alpha stimulated chromosomal loops in the MMP-9 promoter via NFkappaB/p65 and AP-1/c-Jun. The p300-associated acetyltransferase activity was crucial for p65/c-Jun-mediated DNA looping, and inhibition of HDAC activity increased the level of DNA looping. Reduction in the level of DNA looping eliminated all TNF-alpha-stimulated MMP-9 up-regulation. Taken together, our data suggest that p65/c-Jun-mediated DNA looping is involved in TNF-alpha-induced MMP-9 up-regulation and that the recruitment of p300 or HDAC1 to NFkappaB and AP-1 binding sites modifies the level of DNA looping. PMID- 26260844 TI - Dynamic interplay and function of multiple noncoding genes governing X chromosome inactivation. AB - There is increasing evidence for the emergence of long noncoding RNAs (lncRNAs) as important components, especially in the regulation of gene expression. In the event of X chromosome inactivation, robust epigenetic marks are established in a long noncoding Xist RNA-dependent manner, giving rise to a distinct epigenetic landscape on the inactive X chromosome (Xi). The X inactivation center (Xic) is essential for induction of X chromosome inactivation and harbors two topologically associated domains (TADs) to regulate monoallelic Xist expression: one at the noncoding Xist gene and its upstream region, and the other at the antisense Tsix and its upstream region. The monoallelic expression of Xist is tightly regulated by these two functionally distinct TADs as well as their constituting lncRNAs and proteins. In this review, we summarize recent updates in our knowledge of lncRNAs found at the Xic and discuss their overall mechanisms of action. We also discuss our current understanding of the molecular mechanism behind Xist RNA-mediated induction of the repressive epigenetic landscape at the Xi. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa. PMID- 26260846 TI - 14-3-3beta and gamma differentially regulate peroxisome proliferator activated receptor gamma2 transactivation and hepatic lipid metabolism. AB - Peroxisome proliferator activated receptor (PPAR) gamma2 plays important roles in glucose and lipid metabolism in hepatocytes. PPARgamma2 is involved in metabolic disorders, including obesity, diabetes, and fatty liver disease. Although the 14 3-3 proteins participate in a variety of cell signal pathways, the roles of the 14-3-3 proteins in regulating PPARgamma2 transactivation and hepatic lipid metabolism are unknown. We identified 14-3-3beta and gamma as PPARgamma2 transcriptional regulators. We found that 14-3-3beta and gamma competitively interacted with the phosphorylated Ser273 of PPARgamma2, which is important for regulating glucose and lipid metabolism. 14-3-3beta increased the transcriptional activity of PPARgamma2 and enhanced the expression levels of PPARgamma2 target genes involved in lipogenesis and lipid transport. In contrast, 14-3-3gamma decreased PPARgamma2 transactivation and reduced the expression levels of PPARgamma2 target genes. A high concentration of free fatty acids increased PPARgamma2 expression and lipid accumulation. 14-3-3beta enhanced hepatic lipogenesis, which is a major symptom of non-alcoholic fatty liver disease. However, 14-3-3gamma suppressed hepatic lipid accumulation in the presence of high free fatty acids. These findings indicate that 14-3-3beta and gamma are novel PPARgamma2 regulators and are involved in hepatic lipid metabolism. 14-3 3beta and gamma can be therapeutic target molecules to treat non-alcoholic fatty liver disease. PMID- 26260847 TI - Self-Assembled Fluorodendrimers Combine the Features of Lipid and Polymeric Vectors in Gene Delivery. AB - An ideal vector in gene therapy should exhibit high serum stability, excellent biocompatibility, a desired transfection efficacy and permeability into targeted tissues. Here, we describe a class of low-molecular-weight fluorodendrimers for efficient gene delivery. These materials self-assemble into uniform nanospheres and allow for efficient transfection at low charge ratios and very low DNA doses with minimal cytotoxicity. Our results demonstrate that these vectors combine the features of synthetic gene vectors such as liposomes and cationic polymers and present promising potential for clinical gene therapy. PMID- 26260848 TI - The effect of CPAP therapy on insulin-like growth factor and cognitive functions in obstructive sleep apnea patients. AB - OBJECTIVES: Cognitive impairment is common among patients with obstructive sleep apnea syndrome (OSAS). In this study, we aimed to investigate the effect of continuous positive airway pressure (CPAP) therapy on serum insulin-like growth factor-1 (IGF-1) levels and cognitive functions in patients with OSAS. PATIENT/METHODS: Thirty-three patients with newly diagnosed OSAS and 17 healthy control subjects enrolled in the study. All individuals completed the mini-mental state examination (MMSE) to evaluate cognitive function. Blood samples were taken at the end of the polysomnography in the morning and the same procedures were repeated 3 months after starting CPAP treatment. RESULTS: In the OSAS group, the baseline MMSE score was 23.5 +/- 3.6, and serum IGF-1 level was 79.1 +/- 36.1 ng/mL. Both values were significantly lower compared with the control group (mean MMSE score = 28.1 +/- 1.4, P = 0.0001; mean serum IGF-1 level = 147.1 +/- 49.1 ng/mL, P < 0.0001). Three months after CPAP treatment, OSAS patients showed a significant improvement in MMSE scores (26.5 +/- 2.8, P = 0.0001) and serum IGF-1 level (129.1 +/- 58.2, P = 0.0001). In contrast, baseline and third-month measurements for IGF-1 levels and MMSE scores were not significantly different in the control group. CONCLUSIONS: The results indicate that effective CPAP therapy in OSAS patients leads to significant improvement in cognitive functions and IGF 1 even in a short-term follow-up. Cognitive function assessment might be a part of evaluation in OSAS patients. PMID- 26260849 TI - Metformin suppresses intrahepatic coagulation activation in mice with lipopolysaccharide/D-galactosamine-induced fulminant hepatitis. AB - Metformin is a widely-used antidiabetic drug with hypoglycemic activity and previously described anti-inflammatory properties. Previous studies have demonstrated that metformin attenuates endotoxic hepatitis, however the mechanisms remain unclear. Inflammation and coagulation are closely associated pathological processes, therefore the potential effects of metformin on key steps in activation of the coagulation system were further investigated in endotoxic hepatitis induced by lipopolysaccharide/D-galactosamine (LPS/D-Gal). The current study demonstrated that treatment with metformin significantly suppressed the upregulation of tissue factor and plasminogen activator inhibitor-1 in LPS/D-Gal exposed mice. In addition, a reduction in the expression of interleukin 6 and inhibition of nuclear translocation of nuclear factor-kappaB were observed. These data indicate that the LPS/D-Gal-induced elevation of the stable protein level of hypoxia inducible factor 1alpha, the mRNA level of erythropoietin, vascular endothelial growth factor and matrix metalloproteinase-3, and the hepatic level of lactic acid were also suppressed by metformin. The current study indicates that the suppressive effects of metformin on inflammation-induced coagulation may be an additional mechanism underlying the hepatoprotective effects of metformin in mice with LPS/D-Gal-induced fulminant hepatitis. PMID- 26260850 TI - Development of a diagnostic co-dominant marker for stem rust resistance gene Sr47 introgressed from Aegilops speltoides into durum wheat. AB - KEY MESSAGE: A robust and diagnostic STS marker for stem rust resistance gene Sr47 was developed and validated for marker-assisted selection. Stem rust (caused by Puccinia graminis f. sp. tritici, Pgt) resistance gene Sr47, originally transferred from Aegilops speltoides to durum wheat (Triticum turgidum subsp. durum) line DAS15, confers a high level of resistance to Pgt race TTKSK (Ug99). Recently, the durum Rusty 5D(5B) substitution line was used to reduce the Ae. speltoides segment, and the resulting lines had Sr47 on small Ae. speltoides segments on wheat chromosome arm 2BL. The objective of this study was to develop a robust marker for marker-assisted selection of Sr47. A 200-kb segment of the Brachypodium distachyon genome syntenic with the Sr47 region was used to identify wheat expressed sequence tags (ESTs) homologous to the B. distachyon genes. The wheat EST sequences were then used to develop sequence-tagged site (STS) markers. By analyzing the markers for polymorphism between Rusty and DAS15, we identified a co-dominant STS marker, designated as Xrwgs38, which amplified 175 and 187 bp fragments from wheat chromosome 2B and Ae. speltoides chromosome 2S segments, respectively. The marker co-segregated with the Ae. speltoides segments carrying Sr47 in the families from four BC2F1 plants, including the parent plants for durum lines RWG35 and RWG36 with the pedigree of Rusty/3/Rusty 5D(5B)/DAS15//47-1 5D(5B). Analysis of 62 durum and common wheat cultivars/lines lacking the Sr47 segment indicated that they all possessed the 175-bp allele of Xrwgs38, indicating that it was diagnostic for the small Ae. speltoides segment carrying Sr47. This study demonstrated that Xrwgs38 will facilitate the selection of Sr47 in durum and common wheat breeding. PMID- 26260851 TI - Inter-Arm Blood Pressure Differences May Be Important for Predicting Mortality. PMID- 26260852 TI - Fibroelastolytic papulosis: histopathologic confirmation of disease spectrum variants in a single case. AB - Fibroelastolytic papulosis is a rare, acquired fibroelastolytic disorder that presents clinically as white-to-yellow papules and plaques most commonly occurring on the neck of elderly patients. The term fibroelastolytic papulosis encompasses two closely related conditions previously described as pseudoxanthoma elasticum-like papillary dermal elastolysis (PDE) and white fibrous papulosis of the neck (WFPN). Here we present a case of a 78-year-old white female with a several-year history of numerous, asymptomatic 2-3 mm yellowish, non-follicular papules distributed symmetrically over the posterior neck, axillae, arm and antecubital fossae. Histopathologic examination revealed thickened and clumped elastotic fibers admixed with thick, sclerotic appearing collagen bundles in the mid and deep reticular dermis. Rare melanophages, loss of vertically oriented elastic fibers and scattered elastotic globes were noted in the papillary dermis. Based on the shared clinicopathologic features showed in this case, strong consideration should be made for the additional inclusion of papillary dermal elastosis as existing along the disease continuum of fibroelastolytic papulosis. This occurrence of fibroelastolytic papulosis shows unique histopathologic findings of pseudoxanthoma elasticum-like PDE, papillary dermal elastosis and WFPN, further supporting the theory that these entities exist as variants along the fibroelastolytic papulosis spectrum. PMID- 26260853 TI - Active immunization therapies for Parkinson's disease and multiple system atrophy. AB - Vaccination is increasingly being investigated as a potential treatment for synucleinopathies, a group of neurodegenerative diseases including Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies associated with alpha-synuclein pathology. All lack a causal therapy. Development of novel, disease-altering treatment strategies is urgently needed. Vaccination has positioned itself as a prime strategy for addressing these diseases because it is broadly applicable, requires infrequent administration, and maintains low production costs for treating a large population or as a preventive measure. Current evidence points to a causal role of misfolded alpha-synuclein in the development and progression of synucleinopathies. In the past decade, significant progress in active immunization against alpha-synuclein has been shown both in preclinical animal models and in early clinical development. In this review, we describe the state-of-the-art in active immunization approaches to synucleinopathies, with a focus on advances in Parkinson's disease (PD) and multiple-system atrophy (MSA). We first review preclinical animal models, highlighting their progress in translation to the clinical setting. We then discuss current clinical applications, stressing different approaches taken to address alpha-synuclein pathology. Finally, we address challenges, trends, and future perspectives of current vaccination programs. PMID- 26260854 TI - Automating unambiguous NOE data usage in NVR for NMR protein structure-based assignments. AB - Nuclear Magnetic Resonance (NMR) Spectroscopy is an important technique that allows determining protein structure in solution. An important problem in protein structure determination using NMR spectroscopy is the mapping of peaks to corresponding amino acids, also known as the assignment problem. Structure-Based Assignment (SBA) is an approach to solve this problem using a template structure that is homologous to the target. Our previously developed approach Nuclear Vector Replacement-Binary Integer Programming (NVR-BIP) computed the optimal solution for small proteins, but was unable to solve the assignments of large proteins. NVR-Ant Colony Optimization (ACO) extended the applicability of the NVR approach for such proteins. One of the input data utilized in these approaches is the Nuclear Overhauser Effect (NOE) data. NOE is an interaction observed between two protons if the protons are located close in space. These protons could be amide protons, protons attached to the alpha-carbon atom in the backbone of the protein, or side chain protons. NVR only uses backbone protons. In this paper, we reformulate the NVR-BIP model to distinguish the type of proton in NOE data and use the corresponding proton coordinates in the extended formulation. In addition, the threshold value over interproton distances is set in a standard manner for all proteins by extracting the NOE upper bound distance information from the data. We also convert NOE intensities into distance thresholds. Our new approach thus handles the NOE data correctly and without manually determined parameters. We accordingly adapt NVR-ACO solution methodology to these changes. Computational results show that our approaches obtain optimal solutions for small proteins. For the large proteins our ant colony optimization-based approach obtains promising results. PMID- 26260855 TI - A comment on two-locus epistatic interaction models for genome-wide association studies. AB - Detection of epistatic interactions in genome-wide association studies is a computationally hard problem. Many detection algorithms have been proposed and will continue to be. Most of those algorithms measure their predictive power by running on simulated data many times under various disease models. However, we find that there have been subtle differences in interpreting the meaning of existing disease models among the previous studies on detection of epistatic interactions. We elucidate those differences and suggest that future studies on epistatic interactions in GWAS state explicitly which versions/interpretations are employed. We also provide a way to facilitate setting parameters of disease models. PMID- 26260857 TI - Modeling the impact of rubella vaccination in Vietnam. AB - Supported by GAVI Alliance, measles-rubella vaccination was introduced in Vietnam in 2014, involving a mass campaign among 1-14 year olds and routine immunization of children aged 9 months. We explore the impact on the incidence of Congenital Rubella Syndrome (CRS) during 2013-2050 of this strategy and variants involving women aged 15-35 years. We use an age and sex-structured dynamic transmission model, set up using recently-collected seroprevalence data from Central Vietnam, and also consider different levels of transmission and contact patterns. If the serological profile resembles that in Central Vietnam, the planned vaccination strategy could potentially prevent 125,000 CRS cases by 2050 in Vietnam, despite outbreaks predicted in the meantime. Targeting the initial campaign at 15-35 year old women with or without children aged 9 months-14 years led to sustained reductions in incidence, unless levels of ongoing transmission were medium-high before vaccination started. Assumptions about contact greatly influenced predictions if the initial campaign just targeted 15-35 year old women and/or levels of ongoing transmission were medium-high. Given increased interest in rubella vaccination, resulting from GAVI Alliance funding, the findings are relevant for many countries. PMID- 26260856 TI - Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer's disease. AB - Alzheimer's disease (AD) can present with distinct clinical variants. Identifying the earliest neurodegenerative changes associated with each variant has implications for early diagnosis, and for understanding the mechanisms that underlie regional vulnerability and disease progression in AD. We performed voxel based morphometry to detect atrophy patterns in early clinical stages of four AD phenotypes: Posterior cortical atrophy (PCA, "visual variant," n=93), logopenic variant primary progressive aphasia (lvPPA, "language variant," n=74), and memory predominant AD categorized as early age-of-onset (EOAD, <65 years, n=114) and late age-of-onset (LOAD, >65 years, n=114). Patients with each syndrome were stratified based on: (1) degree of functional impairment, as measured by the clinical dementia rating (CDR) scale, and (2) overall extent of brain atrophy, as measured by a neuroimaging approach that sums the number of brain voxels showing significantly lower gray matter volume than cognitively normal controls (n=80). Even at the earliest clinical stage (CDR=0.5 or bottom quartile of overall atrophy), patients with each syndrome showed both common and variant-specific atrophy. Common atrophy across variants was found in temporoparietal regions that comprise the posterior default mode network (DMN). Early syndrome-specific atrophy mirrored functional brain networks underlying functions that are uniquely affected in each variant: Language network in lvPPA, posterior cingulate cortex hippocampal circuit in amnestic EOAD and LOAD, and visual networks in PCA. At more advanced stages, atrophy patterns largely converged across AD variants. These findings support a model in which neurodegeneration selectively targets both the DMN and syndrome-specific vulnerable networks at the earliest clinical stages of AD. PMID- 26260858 TI - Inactivated Salmonella enterica serovar Typhimurium monophasic variant (S. Typhimurium 1,4,[5],12:i-) in sows is effective to control infection in piglets under field condition. AB - The monophasic variant of Salmonella enterica serovar Typhimurium, namely Salmonella 1,4,[5],12:i-, has been increasingly responsible for foodborne human cases of disease and is most frequently detected in pork, since the variant is widely spread in pig farms. The aim of this study was to assess the efficacy of an autologous vaccine in decreasing the prevalence of Salmonella 1,4,[5],12:i-, in pigs. The trial was performed in a multisite pig production system of Northern Italy. The autogenous vaccine was prepared from the Salmonella 1,4,[5],12:i- strain isolated from the clinical case occurring in the Farm. Different immunization protocols were applied, ranging from interventions only in sows or piglets, or both. Microbiological analysis was performed to assess faecal shedding in sows and their offspring from birth till end of the production cycle and organ colonization of slaughtered pigs. Body weight of pigs was recorded at different time-points. Humoral immune response was evaluated in serum samples of sows and piglets. S. Typhimurium 1,4,[5],12:i- determines reduction of animal growth and farm production, furthermore, contamination of carcasses at the slaughterhouse. The load of bacteria entering into the food processing chain is differently influenced by the regimen of administration of inactivated vaccine. In particular, a combined vaccination of sows and their offspring was able to improve the weight gain of growing pigs, to limit Salmonella colonization of organs and to reduce the number of carrier pigs, and hence lowering the risk of introducing Salmonella organisms in the slaughter process. PMID- 26260859 TI - Genetic resistance to infections in sheep. AB - This paper considers genetic resistance to infectious disease in sheep, with appropriate comparison with goats, and explores how such variation may be used to assist in disease control. Many studies have attempted to quantify the extent to which host animals differ genetically in their resistance to infection or in the disease side-effects of infection, using either recorded animal pedigrees or information from genetic markers to quantify the genetic variation. Across all livestock species, whenever studies are sufficiently well powered, then genetic variation in disease resistance is usually seen and such evidence is presented here for three infections or diseases of importance to sheep, namely mastitis, foot rot and scrapie. A further class of diseases of importance in most small ruminant production systems, gastrointestinal nematode infections, is outside the scope of this review. Existence of genetic variation implies the opportunity, at least in principle, to select animals for increased resistance, with such selection ideally used as part of an integrated control strategy. For each of the diseases under consideration, evidence for genetic variation is presented, the role of selection as an aid to disease control is outlined and possible side effects of selection in terms of effects in performance, effects on resistance to other diseases and potential parasite/pathogen coevolution risks are considered. In all cases, the conclusion is drawn that selection should work and it should be beneficial, with the main challenge being to define cost effective selection protocols that are attractive to sheep farmers. PMID- 26260860 TI - Polyketide synthases from poison hemlock (Conium maculatum L.). AB - Coniine is a toxic alkaloid, the biosynthesis of which is not well understood. A possible route, supported by evidence from labelling experiments, involves a polyketide formed by the condensation of one acetyl-CoA and three malonyl-CoAs catalysed by a polyketide synthase (PKS). We isolated PKS genes or their fragments from poison hemlock (Conium maculatum L.) by using random amplification of cDNA ends (RACE) and transcriptome analysis, and characterized three full length enzymes by feeding different starter-CoAs in vitro. On the basis of our in vitro experiments, two of the three characterized PKS genes in poison hemlock encode chalcone synthases (CPKS1 and CPKS2), and one encodes a novel type of PKS (CPKS5). We show that CPKS5 kinetically favours butyryl-CoA as a starter-CoA in vitro. Our results suggest that CPKS5 is responsible for the initiation of coniine biosynthesis by catalysing the synthesis of the carbon backbone from one butyryl-CoA and two malonyl-CoAs. PMID- 26260862 TI - Concordance between nurses' perception of their ability to provide spiritual care and the identified spiritual needs of hospitalized patients: A cross-sectional observational study. AB - Spiritual care is essential to the well-being of patients, and nurses provide spiritual care as a fundamental part of nursing practice. In this study, we investigated the spiritual care needs of hospitalized patients to determine whether the perceived knowledge of nurses corresponded with these spiritual care needs. A cross-sectional study was conducted on 1351 hospitalized patients and 200 registered nurses recruited from a medical center in central Taiwan. A questionnaire, including the 21-item Spiritual Care Needs Inventory (patient and nurse version) and basic demographic information, was distributed to eligible participants. The top three items of the spiritual care needs expressed by the hospitalized patients were respect for privacy and dignity, showing concern, and guidance in gaining a sense of hope in life; the percentages of nurses not knowing how to provide these spiritual care needs were 0%, 1%, and 15%, respectively. The spiritual care needs of patients showed a significant relationship with the knowledge of nurses, suggesting that the perceived knowledge of the nurses generally corresponded with the spiritual care items that the patients required most. PMID- 26260863 TI - Improving dengue viral antigens detection in dengue patient serum specimens using a low pH glycine buffer treatment. AB - BACKGROUND/PURPOSES: Early diagnosis of dengue virus (DENV) infection to monitor the potential progression to hemorrhagic fever can influence the timely management of dengue-associated severe illness. Nonstructural protein 1 (NS1) antigen detection in acute serum specimens has been widely accepted as an early diagnostic assay for dengue infection; however, lower sensitivity of the NS1 antigen-capture enzyme-linked immunosorbent assay (Ag-ELISA) in secondary dengue viral infection has been reported. METHODS: In this study, we developed two forms of Ag-ELISA capable of detecting E-Ag containing virion and virus-like particles, and secreted NS1 (sNS1) antigens, respectively. The temporal kinetics of viral RNA, sNS1, and E-Ag were evaluated based on the in vitro infection experiment. Meanwhile, a panel of 62 DENV-2 infected patients' sera was tested. RESULTS: The sensitivity was 3.042 ng/mL and 3.840 ng/mL for sNS1 and E, respectively. The temporal kinetics of the appearance of viral RNA, E, NS1, and infectious virus in virus-infected tissue culture media suggested that viral RNAs and NS1 antigens could be detected earlier than E-Ag and infectious virus. Furthermore, a panel of 62 sera from patients infected by DENV Serotype 2 was tested. Treating clinical specimens with the dissociation buffer increased the detectable level of E from 13% to 92% and NS1 antigens from 40% to 85%. CONCLUSION: Inclusion of a low-pH glycine buffer treatment step in the commercially available Ag-ELISA is crucial for clinical diagnosis and E-containing viral particles could be a valuable target for acute DENV diagnosis, similar to NS1 detection. PMID- 26260861 TI - 2015 proceedings of the National Heart, Lung, and Blood Institute's State of the Science in Transfusion Medicine symposium. AB - On March 25 and 26, 2015, the National Heart, Lung, and Blood Institute sponsored a meeting on the State of the Science in Transfusion Medicine on the National Institutes of Health (NIH) campus in Bethesda, Maryland, which was attended by a diverse group of 330 registrants. The meeting's goal was to identify important research questions that could be answered in the next 5 to 10 years and which would have the potential to transform the clinical practice of transfusion medicine. These questions could be addressed by basic, translational, and/or clinical research studies and were focused on four areas: the three "classical" transfusion products (i.e., red blood cells, platelets, and plasma) and blood donor issues. Before the meeting, four working groups, one for each area, prepared five major questions for discussion along with a list of five to 10 additional questions for consideration. At the meeting itself, all of these questions, and others, were discussed in keynote lectures, small-group breakout sessions, and large-group sessions with open discourse involving all meeting attendees. In addition to the final lists of questions, provided herein, the meeting attendees identified multiple overarching, cross-cutting themes that addressed issues common to all four areas; the latter are also provided. It is anticipated that addressing these scientific priorities, with careful attention to the overarching themes, will inform funding priorities developed by the NIH and provide a solid research platform for transforming the future practice of transfusion medicine. PMID- 26260865 TI - Taphonomic Patterning of Cemetery Remains Received at the Office of the Chief Medical Examiner, Boston, Massachusetts. AB - A sample of 49 cases of cemetery remains received at the Office of the Chief Medical Examiner, Massachusetts (OCME-MA), in Boston was compared with published taphonomic profiles of cemetery remains. The present sample is composed of a cross section of typical cases in this region that ultimately are derived from modern to historical coffin burials and get turned over to or seized by law enforcement. The present sample was composed of a large portion of isolated remains, and most were completely skeletonized. The most prevalent taphonomic characteristics included uniform staining (77.6%), coffin wear (46.9%), and cortical Exfoliation (49.0%). Other taphonomic changes occurring due to later surface exposure of cemetery remains included subaerial weathering, animal gnawing, algae formation, and excavation marks. A case of one set of skeletal remains associated with coffin artifacts and cemetery offerings that was recovered from transported cemetery fill is also presented. PMID- 26260864 TI - Endoplasmic reticulum stress in diabetic mouse or glycated LDL-treated endothelial cells: protective effect of Saskatoon berry powder and cyanidin glycans. AB - Endoplasmic reticulum (ER) stress is associated with insulin resistance and diabetic cardiovascular complications, and mechanism or remedy for ER stress remains to be determined. The results of the present study demonstrated that the levels of ER stress or unfolded protein response (UPR) markers, the intensity of thioflavin T (ThT) fluorescence and the abundances of GRP78/94, XBP-1 and CHOP proteins were elevated in cardiovascular tissue of diabetic leptin receptor deficient (db/db) mice. Cyanidin-3-glucoside (C3G) and cyanidin-3-galactoside (C3Ga) are major anthocyanins in Saskatoon berry (SB) powder. The administration of 5% SB powder for 4 weeks attenuated ThT fluorescence and the UPR markers in hearts and aortae of wild-type and db/db mice. Treatment with glycated low density lipoprotein (gLDL) increased ThT intensity in human umbilical vein endothelial cells (ECs). Elevated UPR markers were detected in gLDL-treated EC compared to control cultures. The involvement of ER stress in gLDL-treated EC was supported by that the addition of 4-phenyl butyrate acid (a known ER stress antagonist) inhibited gLDL-induced increases in ER stress or UPR markers. C3G at 30 MUM or C3Ga at 100 MUM reached their maximal inhibition on gLDL-induced increases in ThT, GRP78/94, XBP-1 and CHOP in EC. The results demonstrated that ER stress was enhanced in cardiovascular tissue of db/db mice or gLDL-treated EC. SB powder or cyanidin glycans prevented the abnormal increases in ER stress and UPR markers in cardiovascular tissue of diabetic db/db mice or gLDL-treated EC. PMID- 26260866 TI - Tuberculosis (HIV-negative people): improving adherence. AB - INTRODUCTION: About one third of the world's population has immunological evidence of previous exposure to Mycobacterium tuberculosis. In 2013, an estimated 9.0 million people developed tuberculosis (TB) and 1.5 million died from the disease. METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical questions: What are the effects of directly observed treatment (DOT) versus self-administered treatment (SAT) in people with tuberculosis without HIV infection? What are the effects of support mechanisms for DOT in people with tuberculosis without HIV infection? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). RESULTS: At this update, searching of electronic databases retrieved 189 studies. After deduplication and removal of conference abstracts, 104 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 86 studies and the further review of 18 full publications. Of the 18 full articles evaluated, three systematic reviews and one RCT were added at this update. We performed a GRADE evaluation for 12 PICO combinations. CONCLUSIONS: In this systematic overview, we categorised the efficacy for 13 interventions based on information relating to the effectiveness and safety of directly observed treatment and support mechanisms for directly observed treatment. PMID- 26260867 TI - Assessment of pelvic injuries treated with ilio-sacral screws: injury severity and accuracy of screw positioning. AB - PURPOSE: The aim of this study was to analyse possible indicative parameters for percutaneous ilio-sacral stabilisation and to identify parameters associated with screw misplacement. METHODS: Cohort study, level I trauma centre. INCLUSION CRITERIA: (1) unstable pelvic injury, (2) percutaneous ilio-sacral screws placement. EXCLUSION CRITERIA: (1) sacral dysmorphy, (2) failed closed reduction, (3) navigated techniques. Indicative parameters were age, gender, body mass index, number of screws, screw angulation, fracture type and injury severity. End points were ilio-sacral screw position and associated complications. Screw placement accuracy was graded as follows: grade 0, no perforation; grade 1, perforation <2 mm; grade 2, perforation from 2 to 4 mm; grade 3, >=4 mm perforation. RESULTS: Between March 2008 and March 2013, 102 (53 women) patients were included (mean age, 48.5 +/- 21.4 years). The Injury Severity Score (ISS) and New Injury Severity Score (NISS) were 18.9 +/- 9.9 and 22.3 +/- 22.3, respectively. The positions of 137 ilio-sacral screws were analysed. Of all screws, 87.6 % (120) were placed satisfactory (<2 mm perforation). The incidence of screw misplacement was significantly higher in the case of two unilateral S1 screws compared with a single screw (failure rate: two unilateral screws 23.1 % vs single screw 7.0 %; p < 0.05). Screw perforation anterior to the lateral mass (in-out-in) represented the most frequent malposition. Revision was necessary in three cases due to malpositioning. Furthermore, no major complication occurred. CONCLUSIONS: We conclude, that twofold ilio-sacral screw positioning from one side increases the risk for screw misplacement. In this case, alternative techniques like navigation should be considered. Anterior screw perforation represents a common problem with a high incidence and warrants particular attention. PMID- 26260868 TI - Inappropriate interpretations of prenatal drug use data can be worse than the drugs themselves. PMID- 26260869 TI - Association of plasma osteoprotegerin levels with the severity of lower extremity arterial disease in patients with type 2 diabetes. AB - BACKGROUND: Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily and suggested as a marker of atherosclerosis. However, little is known about the association between plasma OPG levels and lower extremity arterial disease. We investigated whether plasma OPG levels were associated with the presence and severity of lower extremity arterial disease in patients with type 2 diabetes. METHODS: This was a study of 712 patients with type 2 diabetes aged 40 years or older. Plasma OPG was measured using ELISA. The lower extremity arterial disease was diagnosed by high-frequency color Doppler ultrasonic. RESULTS: Of 712 patients, 505 (70.9 %) had lower extremity arterial stenosis. OPG levels were significantly increased in patients with lower extremity arterial stenosis [1.89 (1.48-2.41) vs. 2.39 (1.82-3.33) ng/mL, p < 0.001]. Plasma OPG levels increased gradually with increasing severity of lower extremity arterial stenosis (p < 0.001 for trend), after adjustment for traditional cardiovascular risk factors such as age, gender, smoking, total cholesterol, high-density lipoprotein (HDL) cholesterol, C-reactive protein (CRP), body mass index (BMI), systolic blood pressure(SBP). The risk of lower extremity arterial disease was increased (OR = 1.17, 95 % CI 1.09 -1.28, p < 0.001) with each standard deviation (SD) higher level of OPG in patients with type 2 diabetes after adjustment for traditional CVD risk factors. CONCLUSIONS: Plasma OPG levels were significantly associated with the presence and severity of lower extremity arterial disease. Our results suggest that OPG is an important plasma biomarker of lower extremity arterial disease in type 2 diabetes. PMID- 26260870 TI - Developmental exposure of aflatoxin B1 reversibly affects hippocampal neurogenesis targeting late-stage neural progenitor cells through suppression of cholinergic signaling in rats. AB - To elucidate the maternal exposure effects of aflatoxin B1 (AFB1) and its metabolite aflatoxin M1, which is transferred into milk, on postnatal hippocampal neurogenesis, pregnant Sprague-Dawley rats were provided a diet containing AFB1 at 0, 0.1, 0.3, or 1.0 ppm from gestational day 6 to day 21 after delivery on weaning. Offspring were maintained through postnatal day (PND) 77 without AFB1 exposure. Following exposure to 1.0 ppm AFB1, offspring showed no apparent systemic toxicity at weaning, whereas dams showed increased liver weight and DNA repair gene upregulation in the liver. In the hippocampal dentate gyrus of male PND 21 offspring, the number of doublecortin(+) progenitor cells were decreased, which was associated with decreased proliferative cell population in the subgranular zone at >= 0.3 ppm, although T-box brain 2(+) cells, tubulin beta III(+) cells, gamma-H2A histone family, member X(+) cells, and cyclin-dependent kinase inhibitor 1A(+) cells did not fluctuate in number. AFB1 exposure examined at 1.0 ppm also resulted in transcript downregulation of the cholinergic receptor subunit Chrna7 and dopaminergic receptor Drd2 in the dentate gyrus, although there was no change in transcript levels of DNA repair genes. In the hippocampal dentate hilus, interneurons expressing CHRNA7 or phosphorylated tropomyosin receptor kinase B (TRKB) decreased at >= 0.3 ppm. On PND 77, there were no changes in neurogenesis-related parameters. These results suggested that maternal AFB1 exposure reversibly affects hippocampal neurogenesis targeting type-3 progenitor cells. This mechanism likely involves suppression of cholinergic signals on hilar GABAergic interneurons and brain-derived neurotrophic factor TRKB signaling from granule cells. The no-observed-adverse-effect level for offspring neurogenesis was determined to be 0.1 ppm (7.1-13.6 mg/kg body weight/day). PMID- 26260871 TI - 4,5-Dihydro-1,2,3-oxadiazole: A Very Elusive Key Intermediate in Various Important Chemical Transformations. AB - 4,5-Dihydro-1,2,3-oxadiazoles are postulated to be key intermediates in the industrial synthesis of ketones from alkenes, in the alkylation of DNA in vivo, and in the decomposition of N-nitrosoureas; they are also a subject of great interest for theoretical chemists. In the presented report, the formation of 4,5 dihydro-1,2,3-oxadiazole and the subsequent decay into secondary products have been studied by NMR monitoring analysis. The elusive properties evading characterization have now been confirmed by (1) H, (13) C, and (15) N NMR spectroscopy, and relevant 2D experiments at very low temperatures. Our experiments with suitably substituted N-nitrosoureas using thallium(I) alkoxides as bases under apolar conditions answer important questions on the existence and the secondary products of 4,5-dihydro-1,2,3-oxadiazole. PMID- 26260872 TI - Nanostructured Pluronic hydrogels as bioinks for 3D bioprinting. AB - Bioprinting is an emerging technology in the field of tissue engineering as it allows the precise positioning of biologically relevant materials in 3D, which more resembles the native tissue in our body than current homogenous, bulk approaches. There is however a lack of materials to be used with this technology and materials such as the block copolymer Pluronic have good printing properties but do not allow long-term cell culture. Here we present an approach called nanostructuring to increase the biocompatibility of Pluronic gels at printable concentrations. By mixing acrylated with unmodified Pluronic F127 it was possible to maintain the excellent printing properties of Pluronic and to create stable gels via UV crosslinking. By subsequent elution of the unmodified Pluronic from the crosslinked network we were able to increase the cell viability of encapsulated chondrocytes at day 14 from 62% for a pure acrylated Pluronic hydrogel to 86% for a nanostructured hydrogel. The mixed Pluronic gels also showed good printability when cells where included in the bioink. The nanostructured gels were, with a compressive modulus of 1.42 kPa, mechanically weak, but we were able to increase the mechanical properties by the addition of methacrylated hyaluronic acid. Our nanostructuring approach enables Pluronic hydrogels to have the desired set of properties in all stages of the bioprinting process. PMID- 26260873 TI - Chemotherapy is effective for stage I gastric cancer in patients with synchronous esophageal cancer. AB - BACKGROUND: Diagnostic endoscopy occasionally shows synchronous early gastric cancer (EGC) and esophageal cancer (EC) in the same patient. The treatment plan for these comorbid cancers is unclear because, as EGC is commonly treated surgically, information on post-chemotherapy outcomes for EGC are lacking, although chemotherapy and chemoradiotherapy are important in treating EC. Here, we evaluated whether unresected EGC could be safely observed while synchronous EC is treated with chemotherapy in patients with both cancers. METHODS: We enrolled 30 patients with both EGC and EC who were treated with 5-FU plus cisplatin (FP) from January 2006 to September 2013, and who were evaluated with endoscopy before chemotherapy, and approximately every 3 months afterwards. RESULTS: The response rate to FP for EGC was 46.8 %. Notably, five cases (16.7 %) had clinically complete responses with no progressive disease. Progression-free survival was 100 % at 6 months and 96.2 % at 1 year. In univariate analysis, FP was significantly more effective for mixed-type and undifferentiated adenocarcinoma than for differentiated adenocarcinoma. CONCLUSIONS: FP was effective for EGC. EGC was stable without progression for more than 6 months while patients underwent FP treatment for EC. We consider observing EGC with no treatment during chemotherapy for EC to be appropriate disease management. PMID- 26260874 TI - Outcome of gastric cancer in the elderly: a population-based evaluation of the Munich Cancer Registry. AB - BACKGROUND: Gastric cancer accounts for 5 % of cancer deaths. Proportions of older stomach cancer patients are increasing. Despite the still poor prognosis, standardised treatment has achieved improvements; nonetheless it is questionable whether all age groups have benefitted. Age and outcome need to be examined in a population-based setting. METHODS: Analyses included Munich Cancer Registry (MCR) data from 8601 invasive gastric cancer patients, diagnosed between 1998 and 2012. Tumour and therapy characteristics and outcome were analysed by two age groups (<70 vs. >=70 years). Survival was analysed using the Kaplan-Meier method and relative survival was computed as an estimation for cancer-specific survival. Additional landmark analyses were conducted by calculating conditional survival of patients who survived more than 6 months. RESULTS: Fifty-nine per cent of the cohort were >=70 years old. These patients had tumours with a slightly better prognosis and were treated with less radical surgery and adjuvant therapy than younger patients. The 5-year relative survival was 40 % for the youngest (<50 years) and 23 % for the oldest patients (>=80 years). Survival differences were diminished or eliminated after landmark analyses: The 5-year relative survival in age groups 50-59, 60-69 and 70-79 years was comparable (between 48 and 49.6 %) and slightly worse in the youngest and oldest (45 %), which may be explained by more aggressive tumours and effects of cellular senescence, respectively. CONCLUSION: The treatment and care of elderly gastric cancer patients in the MCR catchment area seems appropriate: if a patient's general condition allows oncologic resection and chemotherapy, it is conducted and the result is comparable between age groups. PMID- 26260875 TI - A phase II study of an enhanced recovery after surgery protocol in gastric cancer surgery. AB - BACKGROUND: The enhanced recovery after surgery (ERAS) protocol integrates a number of perioperative interventions and techniques, aiming at decreasing the morbidity rate and the length of postoperative hospital stay after surgery. Although it has become a standard perioperative management for colorectal surgery, the feasibility of the ERAS protocol for gastric surgery remains unclear. METHODS: This single-center, prospective phase II study included patients with gastric cancer undergoing curative gastrectomy. The primary end point was the incidence of Clavien-Dindo grade II or higher postoperative complications. The secondary end points were the incidence of anastomotic leakage, the incidence of pneumonia, the proportion of patients starting oral feeding at postoperative day 2, the completion rate of the ERAS protocol, the length of postoperative hospital stay, the readmission rate within 30 days after discharge, and the mortality rate. RESULTS: From September 2013 to September 2014, 121 eligible patients were enrolled in this study. The incidence of postoperative complications was 10.7 % (90 % confidence interval, 6.47-16.54 %). Anastomotic leakage and pneumonia was observed in one and zero patients, respectively. The median length of postoperative hospital stay was 8 days, and the completion rate of the ERAS protocol was 85.1 %. The readmission rate and the mortality rate were 0 %. CONCLUSIONS: The ERAS protocol can be safely used in patients undergoing gastric cancer surgery. The superiority of the ERAS protocol over non-ERAS perioperative management should be clarified. PMID- 26260877 TI - Responding to heatwave intensity: Excess Heat Factor is a superior predictor of health service utilisation and a trigger for heatwave plans. AB - OBJECTIVE: To determine which measures of heatwave have the greatest predictive power for increases in health service utilisation in Perth, Western Australia. METHODS: Three heatwave formulas were compared, using Poisson or zero-inflated Poisson regression, against the number of presentations to emergency departments from all causes, and the number of inpatient admissions from heat-related causes. The period from July 2006 to June 2013 was included. A series of standardised thresholds were calculated to allow comparison between formulas, in the absence of a gold standard definition of heatwaves. RESULTS: Of the three heatwave formulas, Excess Heat Factor (EHF) produced the most clear dose-response relationship with Emergency Department presentations. The EHF generally predicted periods that resulted in a similar or higher rate of health service utilisation, as compared to the two other formulas, for the thresholds examined. CONCLUSIONS: The EHF formula, which considers a period of acclimatisation as well as the maximum and minimum temperature, best predicted periods of greatest health service demand. The strength of the dose-response relationship reinforces the validity of the measure as a predictor of hazardous heatwave intensity. IMPLICATIONS: The findings suggest that the EHF formula is well suited for use as a means of activating heatwave plans and identifies the required level of response to extreme heatwave events as well as moderate heatwave events that produce excess health service demand. PMID- 26260876 TI - Surgical treatment of liver metastasis of gastric cancer: a retrospective multicenter cohort study (KSCC1302). AB - BACKGROUND: The necessity of surgical treatment of liver metastases of gastric cancer is still controversial. PATIENTS AND METHODS: We conducted a multicenter retrospective cohort study of liver-limited metastasis of gastric cancer treated surgically between 2000 and 2010. In this study, 103 patients were registered, with nine patients excluded from the analysis as they did not meet the eligibility criteria. RESULTS: Of the 94 patients, 69 underwent surgical resection, 11 underwent surgical resection combined with radiofrequency ablation or microwave coagulation therapy for small or deep tumors, and 14 underwent radiofrequency ablation or microwave coagulation therapy only. Synchronous and metachronous metastases were found in 37 and 57 patients, respectively. The 3- and 5-year overall survival rates of all the patients were 51.4 and 42.3 %, respectively. The 3- and 5-year relapse-free survival rates were 29.2 and 27.7 %, respectively. No significant difference in prognosis was observed between the patients who underwent surgical resection and those who underwent ablation therapy. The patients with hepatic solitary lesions and low-grade lymph node metastases of primary gastric cancer had significantly better overall survival and relapse-free survival. CONCLUSIONS: To our knowledge, this study is the largest series and first multicenter cohort study of liver-limited metastasis of gastric cancer. The study indicated that patients with a single liver metastasis with a grade lower than N2 lymph node metastasis of the primary lesion are the best candidates for liver resection. PMID- 26260878 TI - The effects of Bobath-based trunk exercises on trunk control, functional capacity, balance, and gait: a pilot randomized controlled trial. AB - OBJECTIVE: The aim of this study was to investigate the effects of Bobath-based individually designed trunk exercises on trunk control, upper and lower extremity function, and walking and balance in stroke patients. The main aim of treatment was to eliminate individual trunk impairments during various patient functions. METHODS: The study was planned as an assessor-blinded, randomized controlled trial. A total of 22 patients volunteered to participate in the study. Trunk function, functional capacity, and gait were assessed with the Trunk Impairment Scale (TIS), stroke rehabilitation assessment of movement (STREAM), and a 10-m walking test, respectively. The Berg Balance Test (BBT), functional reach (FR), and timed up-and-go (TUG) tests were used to evaluate balance. After the initial assessment, the patients were divided randomly into two groups, the study group (12 patients) and the control group (10 patients). The mean age of the patients in the study group was 55.91 years (duration of stroke 58.66 months) and that of the control group was 54.00 years (duration of stroke 67.20 months). Individual training programs were determined for the patients in the study group, taking into consideration their evaluation results; and strengthening, stretching, range of motion, and mat exercises were determined for the control group according to their functional level. The participants in both groups were taken into the physiotherapy program for 12 weeks, 3 days a week for 1 hour a day. RESULTS: In group analyses, both groups showed improvement in STREAM, TIS, and TUG tests. Only the study group produced significant gains in the BBT, FR, and 10 m walking tests (P < 0.05). According to the pre- and post-treatment results, no significant difference was observed in any of the evaluated parameters between the two groups (P>0.05). CONCLUSION: Individually developed exercise programs in the Bobath concept improve trunk performance, balance, and walking ability in stroke patients more than do conventional exercises. PMID- 26260880 TI - Infectious disease: The natural history of HPV infection in men. PMID- 26260883 TI - Prostate cancer: On the right path--Stat3 signalling controls the ARF-Mdm2-p53 tumour-suppressor pathway. PMID- 26260879 TI - Current and potential urological applications of botulinum toxin A. AB - Botulinum toxin subtype A (BoNT-A) is a potent neurotoxin that can selectively modulate neurotransmitter release from nerve endings, resulting in muscular paralysis. BoNT-A might also act on sensory nerves, and have an anti-inflammatory effect. In the first urological use of BoNT-A, injection into the urethral sphincters of patients with detrusor-sphincter dyssynergia resulted in a reduction of urethral resistance and improved voiding efficiency. Subsequently, intravesical BoNT-A injections have received regulatory approval for treatment of neurogenic detrusor overactivity owing to spinal cord lesions or multiple sclerosis, and idiopathic overactive bladder in adults. BoNT-A has also been widely used to treat patients with the off-label indications of neurogenic or non neurogenic voiding dysfunction and male lower urinary tract symptoms owing to BPH and bladder-neck dysfunction. Other indications for which urologists have applied BoNT-A injections include interstitial cystitis/bladder pain syndrome, bladder oversensitivity and chronic pelvic pain syndrome. BoNT-A is currently delivered as an intravesical injection; however, use of liposome encapsulated formulations is also beginning to show some therapeutic potential. PMID- 26260887 TI - Diagnostic Implementation of Fast and Selective Integrin-Mediated Adhesion of Cancer Cells on Functionalized Zeolite L Monolayers. AB - The rapid and exact identification and quantification of specific biomarkers is a key technology for always achieving more efficient diagnostic methodologies. We present the first application of a nanostructured device constituted of patterned self-assembled monolayers of disk-shaped zeolite L coated with the cyclic integrin ligand c[RGDfK] via isocyanate linker, to the rapid detection of cancer cells. With its high specificity toward HeLa and Glioma cells and fast adhesion ability, this biocompatible monolayer is a promising platform for implementation in diagnostics and personalized therapy formulation devices. PMID- 26260888 TI - Decoupled association between (18)F-FDG and (18)F-FDOPA uptake in a carcinoid of the thymus. PMID- 26260884 TI - Initial prostate cancer diagnosis and disease staging--the role of choline-PET CT. AB - An early and correct diagnosis together with accurate staging of prostate cancer is necessary in order to plan the most appropriate treatment strategy. Morphological imaging modalities such as transrectal ultrasonography (TRUS), CT, and MRI can have some limitations regarding their accuracy for primary diagnosis and staging of prostate cancer; for instance, they have limited specificity in differentiating cancer from benign prostatic conditions and, by using size as the only criterion to characterize lymph node metastases, they might not be accurate enough for tumour characterization. In this scenario, PET-CT with (11)C-labelled or (18)F-labelled choline derivatives provides morphological and functional characterization and could overcome the limitations of the conventional imaging techniques. PET-CT is one of the most investigated molecular imaging modalities for prostate cancer diagnosis and staging. Currently, the main investigations on the role of PET-CT in the diagnosis and staging of prostate cancer have been performed on a retrospective basis and this type of analysis might be one of the main reasons why different results regarding its diagnostic accuracy have been reported. PMID- 26260889 TI - Accuracy of FDG-PET/CT and paraneoplastic antibodies in diagnosing cancer in paraneoplastic neurological syndromes. AB - OBJECTIVE: There is still no consensus about whether to perform PET/CT to detect carcinoma in paraneoplastic neurological syndromes (PNS) in patients with or without antibodies. The aim of this study is to determine the diagnostic accuracy of PET/CT and antibodies in patients with PNS. MATERIAL AND METHODS: A retrospective study was conducted on patients with clinically suspected PNS between 2008 and 2013. The association between histopathological findings, paraneoplastic antibodies, and PET/CT findings were evaluated. Sensitivity and specificity for the detection of underlying malignancy were calculated for PET/CT and paraneoplastic antibodies. RESULTS: A total of 42 patients were analyzed. Of these 42 patients, 32 (75%) had a classical PNS, 6 (14%) had positive PET/CT findings, and 34 were tested for the presence of antibodies (anti-Hu Ab, anti-Yo Ab, and anti-Ri Ab). Twenty one of 34 patients had positive antibodies. Of the 6 patients with positive PET/CT findings, 6 had positive histopathological results. Among 21 patients with positive biomarkers, carcinoma was confirmed only in 5 patients. One patient with negative antibodies, but positive PET/CT findings, was diagnosed with a tumor. Gastric carcinoma was detected in 1 patient with negative PET/CT findings and antibodies during follow-up. Based on the results, PET/CT was found to have 85.71% sensitivity, 100% specificity, 100% positive and 97.22% negative predictive values in the detection of tumors. CONCLUSION: PET/CT has a certain diagnostic accuracy for detecting underlying malignancy in patients with PNS, regardless of the presence of paraneoplastic antibodies. PMID- 26260890 TI - Uncommon isolated distant subcutaneous tissue and skeletal muscle metastasis from oesophageal cancer diagnosed by PET/CT (18)F-FDG. AB - Distant soft-tissue metastases (subcutaneous tissues and skeletal muscle) are extremely rare, particularly in oesophageal carcinoma. The case is described of a patient who was treated for oesophageal adenocarcinoma 2.5 years previously. A PET/CT was performed showing metastatic spread due to a solitary focus of increased tracer uptake corresponding to one subcutaneous node in the upper abdomen. An excisional biopsy showed a metastasis from the carcinoma. Restaging PET/CT (18)F-FDG study was performed 2 year later, demonstrating foci of increased uptake within several muscles as isolated distant haematogenous spread of metastases, histopathologically confirmed. As most of soft-tissue metastases are asymptomatic, the physicians should recommend a histopathological study of focal FDG uptake at subcutaneous tissues and/or skeletal muscles, because they may be the first sign of disease spread, so therapeutic management of these patients could be changed. PMID- 26260891 TI - Exaggerated pulmonary vascular response to acute hypoxia in older men. AB - NEW FINDINGS: What is the central question of this study? Pulmonary arterial pressure is higher in older than younger humans and predicts mortality. It is also increased by acute hypoxia, which causes constriction of the pulmonary vasculature. We asked whether this pulmonary vascular response to hypoxia is greater in older humans. What is the main finding and its importance? Using Doppler echocardiography in 12 younger (~ 20 years old) and nine older men (~ 55 years old) exposed to 20 min of moderate isocapnic hypoxia, we demonstrated that older men showed a significantly greater rise in pulmonary arterial pressure during alveolar hypoxia than younger men. Future studies should examine the pathophysiological importance of increased hypoxic pulmonary vasoconstriction with age. Resting pulmonary arterial pressure increases with age in humans. In the general population, higher values are associated with increased mortality, and in common cardiopulmonary diseases, such as congestive heart failure and chronic obstructive pulmonary disease, the presence of pulmonary arterial hypertension portends a worse outcome. Pulmonary arterial pressure increases during alveolar hypoxia, as a consequence of constriction in the pulmonary vasculature. We hypothesized that older men have more vigorous hypoxic pulmonary vasoconstriction than younger men. Twelve younger (20.5 +/- 0.5 years old) and nine older men (55.8 +/- 2.1 years old) were exposed for 20 min on different days to isocapnic hypoxia (end-tidal PO2 = 50 mmHg) and isocapnic euoxia (end-tidal PO2 = 100 mmHg); each was preceded (baseline) and followed by 5 min of isocapnic euoxia. Systolic pulmonary arterial pressure and cardiac output were measured continuously using Doppler echocardiography. Systolic pulmonary arterial pressure was greater during baseline euoxic measurements in older participants (27.8 +/- 0.8 versus 24.1 +/- 0.7 mmHg, P = 0.001) and also increased more during hypoxia in older participants (15.2 +/- 1.3 versus 9.6 +/- 0.9 mmHg, P = 0.011). Cardiac output did not differ between the two groups during baseline measurements (P = 0.60) or hypoxia (P = 0.49). All data are means +/- SEM. The increased magnitude of hypoxic pulmonary vasoconstriction demonstrated with age has implications for individuals wishing to ascend to high altitude or travel by air, for those suffering from conditions in which global alveolar hypoxia is a feature and for patients requiring general anaesthesia. PMID- 26260892 TI - Glutathione Decrement Drives Thermogenic Program In Adipose Cells. AB - Adipose tissue metabolically adapts to external stimuli. We demonstrate that the induction of the thermogenic program in white adipocytes, through cold exposure in mice or in vitro adrenergic stimulation, is accompanied by a decrease in the intracellular content of glutathione (GSH). Moreover, the treatment with a GSH depleting agent, buthionine sulfoximine (BSO), recapitulates the effect of cold exposure resulting in the induction of thermogenic program. In particular, BSO treatment leads to enhanced uncoupling respiration as demonstrated by increased expression of thermogenic genes (e.g. Ucp1, Ppargc1a), augmented oxygen consumption and decreased mitochondrial transmembrane potential. Buffering GSH decrement by pre-treatment with GSH ester prevents the up-regulation of typical markers of uncoupling respiration. We demonstrate that FoxO1 activation is responsible for the conversion of white adipocytes into a brown phenotype as the "browning" effects of BSO are completely abrogated in cells down-regulating FoxO1. In mice, the BSO-mediated up-regulation of uncoupling genes results in weight loss that is at least in part ascribed to adipose tissue mass reduction. The induction of thermogenic program has been largely proposed to counteract obesity-related diseases. Based on these findings, we propose GSH as a novel therapeutic target to increase energy expenditure in adipocytes. PMID- 26260893 TI - Immunogenic properties of Landrace pigs selected for resistance to mycoplasma pneumonia of swine. AB - Mycoplasma pneumonia of swine (MPS) lung lesions and immunogenic properties were compared between a Landrace line that was genetically selected for reduced incidence of pulmonary MPS lesions, and a non-selected Landrace line. The MPS selected Landrace line showed significantly lower degrees of pulmonary MPS lesions compared with the non-selected Landrace line. When changes in immunity before and after vaccination were compared, the percentage of B cells in the peripheral blood of the MPS-selected Landrace line was significantly lower than that of the non-selected line. Furthermore, the concentration of growth hormone and the mitogen activity of peripheral blood mononuclear cells in the MPS selected Landrace line showed significantly (P < 0.05) lower increases after vaccination than the non-selected line. Conversely, the concentration of peripheral blood interferon (IFN)-gamma and salivary immunoglobulin A (IgA) after Mycoplasma hyopneumoniae vaccination was significantly higher in the MPS-selected Landrace line than in the non-selected line. Gene expression of toll-like receptor (TLR)2 and TLR4 was significantly higher in the MPS-selected Landrace line in immune tissues, with the exception of the hilar lymph nodes. The present results suggest that peripheral blood IFN-gamma, salivary IgA TLR2, and TLR4 are important immunological factors influencing the development of MPS lesions. PMID- 26260894 TI - Evaluation of clinical trial of atopic dermatitis by a topical cream containing the extracts from photosynthetic bacteria, Rhodobacter sphaeroides. AB - The photosynthetic bacteria Rhodobacter sphaeroides has been studied as a functional food source; however, in this clinical study, we report for the first time its use as a treatment for atopic dermatitis. Topical cream containing 10% (v/v) extract was demonstrated to have the ability to reduce skin moisture content loss and pruritus by 27.82% in clinical trials for atopic dermatitis compared with controls. In particular, there were statistically significant differences in the pH and temperature changes of the skin, skin firmness and general skin appearance. Changes in the skin pH were measured as 4.83, and there was a 3.37% change in temperature after 4 weeks of treatment. It was also found that there were great differences in wrinkle states according to the grading scale of patients before and after treatment with topical cream. Therefore, these results strongly suggest that extracts from photosynthetic bacteria can be employed to soothe atopic irritation as a new cosmetic bioresource. PMID- 26260895 TI - A qPCR and multiplex pyrosequencing assay combined with automated data processing for rapid and unambiguous detection of ESBL-producers Enterobacteriaceae. AB - Rapid and specific detection of extended-spectrum beta-lactamase-producing (ESBL) bacteria is crucial both for timely antibiotic therapy when treating infected patients as well as for appropriate infection control measures aimed at curbing the spread of ESBL-producing isolates. Whereas a variety of phenotypic methods are currently available for ESBL detection, they remain time consuming and sometimes difficult to interpret while being also affected by a lack of sensitivity and specificity. Considering the longer turnaround time (TAT) of susceptibility testing and culture results, DNA-based ESBL identification would be a valuable surrogate for phenotypic-based methods. Putative ESBL-positive Enterobacteriaceae isolates (n = 330) from clinical specimen were prospectively collected in Bulgaria, Romania and Democratic Republic of Congo and tested in this study. All isolates were assessed for ESBL-production by the E-test method and those giving undetermined ESBL status were re-tested using the combination disk test. A genotypic assay successively combining qPCR detection of blaCTX-M, blaTEM and blaSHV genes with a multiplex pyrosequencing of blaTEM and blaSHV genes was developed in order to detect the most common ESBL-associated TEM and SHV single nucleotides polymorphisms, irrespective of their plasmid and/or chromosomal location. This assay was applied on all Enterobacteriaceae isolates (n = 330). Phenotypic and genotypic results matched in 324/330 (98.2%). Accordingly, real-time PCR combined with multiplex pyrosequencing appears to be a reliable and easy-to-perform assay with high-throughput identification and fast TAT (~5 h). PMID- 26260896 TI - Schizophrenia and the influence of male gender. AB - Adolescent boys are the demographic group most likely to receive a diagnosis of schizophrenia. Before adulthood, boys accumulate more potential brain hazards than girls, and this may predispose them to disordered neurodevelopment during adolescence. Hormonal and immune gender differences that emerge at this time likely play an additional and significant role. Very recently, gender differences can be examined even before the onset of full-blown illness, in individuals at "clinically high risk." PMID- 26260897 TI - The small heat shock protein, HSP30, is associated with aggresome-like inclusion bodies in proteasomal inhibitor-, arsenite-, and cadmium-treated Xenopus kidney cells. AB - In the present study, treatment of Xenopus laevis A6 kidney epithelial cells with the proteasomal inhibitor, MG132, or the environmental toxicants, sodium arsenite or cadmium chloride, induced the accumulation of the small heat shock protein, HSP30, in total and in both soluble and insoluble protein fractions. Immunocytochemical analysis revealed the presence of relatively large HSP30 structures primarily in the perinuclear region of the cytoplasm. All three of the stressors promoted the formation of aggresome-like inclusion bodies as determined by immunocytochemistry and laser scanning confocal microscopy using a ProteoStat aggresome dye and additional aggresomal markers, namely, anti-gamma-tubulin and anti-vimentin antibodies. Further analysis revealed that HSP30 co-localized with these aggresome-like inclusion bodies. In most cells, HSP30 was found to envelope or occur within these structures. Finally, we show that treatment of cells with withaferin A, a steroidal lactone with anti-inflammatory, anti-tumor, and proteasomal inhibitor properties, also induced HSP30 accumulation that co localized with aggresome-like inclusion bodies. It is possible that proteasomal inhibitor or metal/metalloid-induced formation of aggresome-like inclusion bodies may sequester toxic protein aggregates until they can be degraded. While the role of HSP30 in these aggresome-like structures is not known, it is possible that they may be involved in various aspects of aggresome-like inclusion body formation or transport. PMID- 26260898 TI - Delayed access of low body weight-selected chicks to food at hatch is associated with up-regulated pancreatic glucagon and glucose transporter gene expression. AB - Chickens selected for low (LWS) and high (HWS) juvenile body weight (BW) for 55 generations differ in BW by 10-fold at selection age. High (HWR) and low (LWR) body weight-relaxed lines have been random-bred since the 46th generation. Our objective was to evaluate the developmental and nutritional regulation of pancreatic mRNA abundance of pancreatic and duodenal homeobox 1 (PDX1), preproinsulin (PPI), preproglucagon (PPG), and glucose transporter 2 (GLUT2). At day of hatch (DOH) and days 1, 3, 7, and 15 (D1, 3, 7 and 15, respectively), pancreas was collected and real time PCR was performed in Experiment 1. In Experiment 2, HWS and LWS were fed or delayed access to food for 72 h post-hatch, and pancreas collected at D15. There was an interaction of line and age for GLUT2 (P=0.001), PPI (P<0.0001), PPG (P=0.034), and PDX1 (P<0.0001). Expression was greater in chicks from LWR and LWS than HWR and HWS. There was an interaction of line and nutrition on PPG (P<0.0001) and GLUT2 (P=0.001) mRNA, where expression was similar among chicks that were fed but greater in LWS than HWS when chicks were delayed access to food. Thus, the first two weeks is important for maturation of pancreatic endocrine function. Long-term selection for BW is associated with differences in pancreas development, and delaying access to food at hatch may have persisting effects on glucose regulatory function. PMID- 26260899 TI - Neurocognitive impairment in the deficit subtype of schizophrenia. AB - Schizophrenia is a heterogeneous disorder characterized by numerous diverse signs and symptoms. Individuals with prominent, persistent, and idiopathic negative symptoms are thought to encompass a distinct subtype of schizophrenia. Previous work, including studies involving neuropsychological evaluations, has supported this position. The present study sought to further examine whether deficit patients are cognitively distinct from non-deficit patients with schizophrenia. A comprehensive neurocognitive battery including tests of verbal memory, vigilance, processing speed, reasoning, and working memory was administered to 657 patients with schizophrenia. Of these, 144 (22 %) patients were classified as deficit patients using a proxy identification method based on severity, persistence over time, and possible secondary sources (e.g., depression) of negative symptoms. Deficit patients with schizophrenia performed worse on all tests of cognition relative to non-deficit patients. These patients were characterized by a generalized cognitive impairment on the order of about 0.4 standard deviations below that of non-deficit patients. However, when comparing deficit patients to non-deficit patients who also present with negative symptoms, albeit not enduring or primary, no group differences in cognitive performance were found. Furthermore, a discriminant function analysis classifying patients into deficit/non-deficit groups based on cognitive scores demonstrated only 62.3 % accuracy, meaning over one-third of individuals were misclassified. The deficit subtype of schizophrenia is not markedly distinct from non-deficit schizophrenia in terms of neurocognitive performance. While deficit patients tend to have poorer performance on cognitive tests, the magnitude of this effect is relatively modest, translating to over 70 % overlap in scores between groups. PMID- 26260900 TI - Altered intrinsic organisation of brain networks implicated in attentional processes in adult attention-deficit/hyperactivity disorder: a resting-state study of attention, default mode and salience network connectivity. AB - Deficits in task-related attentional engagement in attention deficit/hyperactivity disorder (ADHD) have been hypothesised to be due to altered interrelationships between attention, default mode and salience networks. We examined the intrinsic connectivity during rest within and between these networks. Six-minute resting-state scans were obtained. Using a network-based approach, connectivity within and between the dorsal and ventral attention, the default mode and the salience networks was compared between the ADHD and control group. The ADHD group displayed hyperconnectivity between the two attention networks and within the default mode and ventral attention network. The salience network was hypoconnected to the dorsal attention network. There were trends towards hyperconnectivity within the dorsal attention network and between the salience and ventral attention network in ADHD. Connectivity within and between other networks was unrelated to ADHD. Our findings highlight the altered connectivity within and between attention networks, and between them and the salience network in ADHD. One hypothesis to be tested in future studies is that individuals with ADHD are affected by an imbalance between ventral and dorsal attention systems with the former playing a dominant role during task engagement, making individuals with ADHD highly susceptible to distraction by salient task irrelevant stimuli. PMID- 26260902 TI - Genome wide DNA copy number analysis in cholangiocarcinoma using high resolution molecular inversion probe single nucleotide polymorphism assay. AB - In order to study molecular similarities and differences of intrahepatic (IH-CCA) and extrahepatic (EH-CCA) cholangiocarcinoma, 24 FFPE tumor samples (13 IH-CCA, 11 EH-CCA) were analyzed for whole genome copy number variations (CNVs) using a new high-density Molecular Inversion Probe Single Nucleotide Polymorphism (MIP SNP) assay. Common in both tumor subtypes the most frequent losses were detected on chromosome 1p, 3p, 6q and 9 while gains were mostly seen in 1q, 8q as well as complete chromosome 17 and 20. Applying the statistical GISTIC (Genomic Identification of Significant Targets in Cancer) tool we identified potential novel candidate tumor suppressor- (DBC1, FHIT, PPP2R2A) and oncogenes (LYN, FGF19, GRB7, PTPN1) within these regions of chromosomal instability. Next to common aberrations in IH-CCA and EH-CCA, we additionally found significant differences in copy number variations on chromosome 3 and 14. Moreover, due to the fact that mutations in the Isocitrate dehydrogenase (IDH-1 and IDH-2) genes are more frequent in our IH-CCA than in our EH-CCA samples, we suggest that the tumor subtypes have a different molecular profile. In conclusion, new possible target genes within regions of high significant copy number aberrations were detected using a high-density Molecular Inversion Probe Single Nucleotide Polymorphism (MIP SNP) assay, which opens a future perspective of fast routine copy number and marker gene identification for gene targeted therapy. PMID- 26260901 TI - Are morphological changes necessary to mediate the therapeutic effects of electroconvulsive therapy? AB - The neurotrophic hypothesis has become the favorite model to explain the antidepressant properties of electroconvulsive therapy (ECT). It is based on the assumption that a restoration of previously defective neural networks drives therapeutic effects. Recent data in rather young patients suggest that neurotrophic effects of ECT might be detectable by diffusion tensor imaging. We here aimed to investigate whether the therapeutic response to ECT necessarily goes along with mesoscopic effects in gray matter (GM) or white matter (WM) in our patients in advanced age. Patients (n = 21, 15 males and 7 females) suffering from major depressive disorder were treated with ECT. Before the start of treatment and after the completion of the index series, they underwent magnetic resonance imaging, including a diffusion-weighed sequence. We used voxel-based morphometry to assess GM changes and tract-based spatial statistics and an SPM based whole-brain analysis to detect WM changes in the course of treatment. Patients significantly improved clinically during the course of ECT. This was, however, not accompanied by GM or WM changes. This result challenges the notion that mesoscopic brain structure changes are an obligatory prerequisite for the antidepressant effects of ECT. PMID- 26260903 TI - Increased DNA methylation in the livers of patients with alcoholic hepatitis. AB - Epigenetic regulation of gene expression has been suggested to play a critical role in the development of alcoholic hepatitis (AH). Although it has been shown that ethanol-induced damage in hepatocytes resulted from a change in methionine metabolism causes global gene expression changes in hepatocytes, the role of the epigenetic machinery in such processes has, however, been barely investigated. 5 Methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are major molecules of epigenetic DNA modification that play an important role in the control of gene expression. Using antibodies against 5mC and 5hmC, the DNA methylation in patients with AH was examined by immunohistochemistry and quantified by morphometric image analysis. The immunoreactivity intensity of 5mC in patients with AH was significantly higher than that seen in normal controls. While there was a trend of decreased 5-hmC in patients with AH, the difference between patients with AH and normal control was not significant. Our study suggests that aberrant DNA-methylation is associated with pathogenesis of AH. PMID- 26260905 TI - Metaproteomic evidence of changes in protein expression following a change in electrode potential in a robust biocathode microbiome. AB - Microorganisms that respire electrodes may be exploited for biotechnology applications if key pathways for extracellular electron transfer can be identified and manipulated through bioengineering. To determine whether expression of proposed Biocathode-MCL extracellular electron transfer proteins are changed by modulating electrode potential without disrupting the relative distribution of microbial constituents, metaproteomic and 16S rRNA gene expression analyses were performed after switching from an optimal to suboptimal potential based on an expected decrease in electrode respiration. Five hundred and seventy-nine unique proteins were identified across both potentials, the majority of which were assigned to three previously defined Biocathode-MCL metagenomic clusters: a Marinobacter sp., a member of the family Chromatiaceae, and a Labrenzia sp (abbreviated as MCL). Statistical analysis of spectral counts using the Fisher's exact test identified 16 proteins associated with the optimal potential, five of which are predicted electron transfer proteins. The majority of proteins associated with the suboptimal potential were involved in protein turnover/synthesis, motility, and membrane transport. Unipept and 16S rRNA gene expression analyses indicated that the taxonomic profile of the microbiome did not change after 52 h at the suboptimal potential. These findings show that protein expression is sensitive to the electrode potential without inducing shifts in community composition, a feature that may be exploited for engineering Biocathode-MCL. All MS data have been deposited in the ProteomeXchange with identifier PXD001590 (http://proteomecentral.proteomexchange.org/dataset/PXD001590). PMID- 26260904 TI - IL-8 signaling is up-regulated in alcoholic hepatitis and DDC fed mice with Mallory Denk Bodies (MDBs) present. AB - Chemokines and their receptors are involved in oncogenesis and in tumor progression, invasion, and metastasis. Various chemokines also promote cell proliferation and resistance to apoptosis of stressed cells. The chemokine CXCL8, also known as interleukin-8 (IL-8), is a proinflammatory molecule that has functions within the tumor microenvironment. Deregulation of IL-8 signaling is shown to play pivotal roles in tumorigenesis and progression. Mallory-Denk Bodies (MDBs) are prevalent in various liver diseases including alcoholic hepatitis (AH) and are formed in mice livers by feeding DDC. By comparing AH livers where MDBs had formed with normal livers, there were significant changes of IL-8 signaling by RNA sequencing (RNA-Seq) analyses. Real-time PCR analysis of CXCR2 further shows a 6-fold up-regulation in AH livers and a 26-fold up-regulation in the livers of DDC re-fed mice. IL-8 mRNA was also significantly up-regulated in AH livers and DDC re-fed mice livers. This indicates that CXCR2 and IL-8 may be crucial for liver MDB formation. MDB containing balloon hepatocytes in AH livers had increased intensity of staining of the cytoplasm for both CXCR2 and IL-8. Overexpression of IL-8 leads to an increase of the mitogen activated protein kinase (MAPK) cascade and exacerbates the inflammatory cycle. These observations constitute a demonstration of the altered regulation of IL-8 signaling in the livers of AH and mice fed DDC where MDBs formed, providing further insight into the mechanism of MDB formation mediated by IL-8 signaling in AH. PMID- 26260906 TI - Galectin-9 suppresses cholangiocarcinoma cell proliferation by inducing apoptosis but not cell cycle arrest. AB - Cholangiocarcinoma is the most common biliary malignancy and the second most common hepatic malignancy after hepatocellular carcinoma (HCC). Galectin-9 (Gal 9) is a tandem-repeat-type galectin that has recently been shown to exert antiproliferative effects on cancer cells. Therefore, the present study evaluated the effects of Gal-9 on the proliferation of human cholangiocarcinoma cells in vitro as well as the microRNAs (miRNAs) associated with the antitumor effects of Gal-9. Gal-9 suppressed the proliferation of cholangiocarcinoma cell lines in vitro and the growth of human cholangiocarcinoma cell xenografts in nude mice. Our data further revealed that Gal-9 increased caspase-cleaved keratin 18 (CCK18) levels, and the expression of cytochrome c increased in Gal-9-treated cholangiocarcinoma cell lines. These data suggested that Gal-9 induced cholangiocarcinoma cell apoptosis via the intrinsic apoptosis pathway mediated by caspase-dependent or -independent pathways. In addition, Gal-9 reduced the phosphorylation of the epidermal growth factor receptor (EGFR), insulin-like growth factor and insulin-like growth factor-1 receptor (IGF-1R), hepatocyte growth factor receptor and fibroblast growth factor receptor 3 (FGFR3). These findings suggest that Gal-9 can be a candidate of therapeutic target in the treatment of cholangiocarcinoma. PMID- 26260907 TI - The Use of Intraoperative Dexmedetomidine Is Not Associated With a Reduction in Acute Kidney Injury After Lung Cancer Surgery. AB - OBJECTIVE: To evaluate whether the use of intraoperative dexmedetomidine (DEX) during lung cancer surgery may reduce the incidence of acute kidney injury (AKI). DESIGN: A retrospective study. SETTING: An academic hospital. PARTICIPANTS: Data were collected from 1,207 adult patients who underwent resection for non-small cell lung cancer between January 2004 and December 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients had a general balanced anesthetic technique, and dexmedetomidine use was at the discretion of the anesthesiologist. Data analysis was done utilizing the Wilcoxon rank sum tests and Chi-square tests to compare continuous variables and categoric variables between the 2 groups, respectively. Multivariate logistic analysis with backward selection was fitted to find out factors for AKI incidence. Overall, 8.1% of the patients developed AKI during their hospital stay. There were no statistically significant differences in demographic, perioperative variables, and the incidence of AKI between patients who did and did not receive DEX. A logistic regression model was fitted to determine factors independently associated with AKI. Factors that were independently associated with AKI included body mass index, American Society of Anesthesiologists 3-4, hypertension, smoking status, and thoracotomy procedure. DISCUSSION: The authors hypothesized that DEX use would be associated with a decreased incidence of AKI in thoracic surgery; however, they were unable to prove this hypothesis. Their results did demonstrate that there are 5 factors independently associated with AKI. PMID- 26260908 TI - Reply to van Oosten et al: "P-Wave Characteristics on Routine Preoperative Electrocardiogram Improve Prediction of New-Onset Postoperative Atrial Fibrillation in Cardiac Surgery". PMID- 26260909 TI - Neratinib shows efficacy in the treatment of HER2 amplified carcinosarcoma in vitro and in vivo. AB - OBJECTIVE: Carcinosarcoma is a deadly gynecologic malignancy with few effective treatment options. The study of new therapies is difficult because of its rarity. The objective of this study was to determine the efficacy of neratinib in the treatment of HER2 amplified carcinosarcoma. METHODS: The efficacy of neratinib in the treatment of HER2 amplified carcinosarcoma was determined in vitro using seven primary carcinosarcoma cell lines with differential expression of HER2/neu. Data regarding IC50, cell cycle distribution, and cell signaling changes were assessed by flow cytometry. The efficacy of neratinib was determined in treating mice harboring HER2 amplified carcinosarcoma xenografts. RESULTS: Two of seven (28.5%) carcinosarcoma cell lines were HER2/neu amplified. HER2/neu amplified cell lines SARARK6 and SARARK9 were significantly more sensitive to neratinib than the five non-HER2/neu amplified carcinosarcoma cell lines (mean+/-SEM IC50:0.014MUM+/-0.004vs.0.164MUM+/-0.019 p=0.0003). Neratinib treatment caused a significant build up in G0/G1 phase of the cell cycle, arrest auto phosphorylation of HER2/neu and activation of S6. Neratinib inhibited tumor growth (p=0.012) and prolonged survival in mice harboring HER2 amplified carcinosarcoma xenografts (p=0.0039). CONCLUSIONS: Neratinib inhibits HER2 amplified carcinosarcoma proliferation, signaling, cell cycle progression and tumor growth in vitro. Neratinib inhibits HER2/neu amplified xenograft growth and improves overall survival. Clinical trials are warranted. PMID- 26260910 TI - Prognostic significance of differential expression of angiogenic genes in women with high-grade serous ovarian carcinoma. AB - OBJECTIVES: To identify angiogenic biomarkers associated with tumor angiogenesis and clinical outcome in high-grade serous ovarian cancer (HGSC). METHODS: 51 HGSC samples were analyzed using Affymetrix HG-U133A microarray. Microvessel density (MVD) counts were determined using CD31 and CD105. Associations between mRNA expression levels and overall survival were assessed using rank score statistic. Effect size was estimated as a hazard ratio (HR) under a proportional hazard model. The Storey q-value method was used to account for multiple testing within the false-discovery rate (FDR) framework. Publicly available databases including TCGA and GSE were used for external confirmation. RESULTS: Thirty-one angiogenic related genes were significantly associated with survival (q<=0.05). Of these 31 genes, 4 were also associated with outcome in the TCGA data: AKT1 (q=0.02; TCGA p=0.01, HR=0.8), CD44 (q=0.003; TCGA p=0.05, HR=0.9), EPHB2 (q=0.01; TCGA p=0.05, HR=1.2), and ERBB2 (q=0.02; TCGA p=0.05, HR=1.2). While 5 were associated with outcome in the GSE database: FLT1 (q=0.03; GSE26712 p=0.01, HR=3.1); PF4 (q=0.02; GSE26712 p=0.01, HR=3.0); NRP1 (q=0.02; GSE26712 p<0.04, HR>1.4); COL4A3 (q=0.04; GSE26712 p=0.03, HR=1.3); and ANGPTL3 (q=0.02; GSE14764 p=0.02, HR=1.5). High AKT1 and CD44 were associated with longer survival. In contrast, high expression of EPHB2, ERBB2, FLT1; PF4, NRP1, COL4A3, and ANGPTL3 were associated with shorter survival. CD105-MVD and CD31-MVD were not significantly associated with angiogenic gene expression. CONCLUSIONS: Thirty-one angiogenic-related genes were associated with survival in advanced HGSC and nine of these genes were confirmed in independent publicly available databases. PMID- 26260911 TI - Metabolic syndrome is an independent prognostic factor for endometrial adenocarcinoma. AB - OBJECTIVE: To study the association between metabolic syndrome (MS) and the prognosis of patients with endometrial adenocarcinoma. METHODS: A total of 385 patients with endometrial adenocarcinoma in the Department of Gynecologic Oncology, at the Zhejiang Cancer Hospital in China, between January 2001 and December 2008 were chosen. The deadline for the completion of follow-up was December 2013. The overall survival (OS) of the patients with MS was analyzed by the Kaplan-Meier method. Various clinical characteristics (e.g., clinical and surgical stage, vascular invasion, histological grade, tumor size, age at start of the first treatment, and lymphatic metastasis) related to the prognosis of endometrial adenocarcinoma were also evaluated. RESULTS: A univariate analysis demonstrated that the OS rate of the patients with endometrial adenocarcinoma with MS was significantly worse than that of the patients without MS for all 385 patients (P = 0.001). Multivariate Cox proportional hazards regression analyses showed that stage (P = 0.001), lymphatic metastasis (P = 0.021), and MS (P = 0.049) were independent prognostic factors for endometrial adenocarcinoma. Furthermore, statistical analyses demonstrated that MS was closely related to stage (P = 0.021), grade (P = 0.022), vascular invasion (P = 0.044), tumor size (P = 0.035), and lymphatic metastasis (P = 0.014) but not with age at start of the first treatment (P = 0.188). Finally, according to the univariate analysis of the OS rate of 129 cases of endometrial adenocarcinoma with MS, stage (P = 0.001), vascular invasion (P = 0.049), tumor size >2 cm (P = 0.028), lymphatic metastasis (P = 0.002), and CA19-9 value >37 U/m (P = 0.002) all showed significantly low P values for OS. CONCLUSION: Metabolic syndrome is an independent prognostic factor for endometrial adenocarcinoma. PMID- 26260912 TI - Colorectal cancer metastatic to the brain: analysis of prognostic factors and impact of KRAS mutations on presentation and outcome. AB - BACKGROUND: Treatment concepts for metastatic colorectal cancer continue to evolve. While the presence of RAS mutations impacts systemic therapy, little is known about the influence of such mutations in patients with brain metastases. PATIENTS AND METHODS: Pooled retrospective analysis was conducted of 57 patients with brain metastases from colorectal cancer treated in two different institutions (2005-2013). RESULTS: The only mutations analyzed in a relatively large subgroup were KRAS mutations (14 wild type, 12 mutated). Mutation status was not associated with baseline characteristics such as number or location of metastases, and did not impact prognosis. Three factors were significantly associated with survival in multivariate analysis: Karnofsky Performance Status (KPS), management strategy, and systemic treatment. Median survival was 0.6 months with best supportive care, 3.0 months with initial whole-brain radiotherapy (WBRT), and 12.7 months if initial treatment included surgery or stereotactic radiosurgery (SRS), p = 0.0001. The survival difference between the WBRT and surgery/SRS groups was largest in patients with KPS 80-100. CONCLUSION: Effective local treatment was a prerequisite for improved survival. The only significant prognostic baseline factor was KPS, which forms the basis of the diagnosis-specific graded prognostic assessment (DS-GPA) score. Thus, our results validate the DS-GPA in this patient population. So far, neither this nor other studies suggest a clinically important impact of KRAS mutations beyond their previously reported association with development of brain metastases. Studies focusing on patients who develop brain metastases early during the course of metastatic disease might be warranted, because the influence of different systemic therapies might be larger in this subgroup. PMID- 26260913 TI - Epstein-Barr virus-encoded small RNA 1 (EBER-1) could predict good prognosis in nasopharyngeal carcinoma. AB - PURPOSE: EBER-1 (a non-coding RNA transcribed by EBV) expression was detected in most of Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) patients. However, the relevance between EBER-1 expression and NPC clinical outcome has not been reported. This study aims to assess the possible correlations of EBER-1 expression and clinical parameters and its potential prognostic predictive ability in NPC patient's outcomes. METHODS: We examined EBER-1 mRNA expression in 301 NPC and 130 non-NPC tissues using in situ hybridization and did statistics. RESULTS: EBER-1 expression was up-regulated in NPC tissues when compared to non-NPC tissues. A receiver operating characteristic analysis revealed that EBER-1 expression could distinguish non-cancerous patients from NPC patients (p < 0.001, sensitivity: 72.5 %, specificity: 83.5 %, AUC = 0.815). A survival analysis revealed that patients with high levels of EBER-1 expression had a significantly good prognosis (Disease-free survival: p = 0.019, overall survival: p = 0.006). CONCLUSION: These results indicated that EBER-1 expression is a potential prognosis factor of NPC and highly negative correlated with the progress of NPC. PMID- 26260914 TI - Methylation of ASC/TMS1 promoter is associated with poor prognosis of patients with gastric cancer. AB - OBJECTIVE: This study was conducted to explore the prognostic value of the methylation status of the ASC/TMS1 (apoptosis-associated speck-like protein containing a CARD/the target of methylation-induced silencing-1) promoter in gastric cancer (GC). METHODS: ASC/TMS1 expression was detected in GC tissues and normal gastric mucosal tissues by real-time quantitative PCR and Western blot analysis. Methylation-specific PCR (MSP) analysis was performed to detect the methylated degrees of the DNA of the ASC/TMS1 promoter of 200 GC patients. Associations between molecular, clinicopathological characteristics and survival data were analyzed. RESULTS: The mRNA and protein expression levels of ASC/TMS1 in GC tissues were lower than those in normal gastric mucosal tissues. With the MSP detection, ASC/TMS1 promoter methylation was found in 68 (34 %) in 200 GC tissues, while none of 40 normal gastric mucosal tissues were found to be methylated. The size of primary tumor and lymph node metastasis were identified as independent relative factors of methylation status of the ASC/TMS1 promoter in GC tissues. Multivariate analysis results demonstrated that the degree of differentiation, serosal invasion, lymph node metastasis and methylated status of ASC/TMS1 promoter were independent prognostic indicators of GC. Lymph node metastasis and methylated status of ASC/TMS1 promoter were optimal prognostic predictors of GC patients, as identified by Cox regression with Akaike information criterion value calculation. CONCLUSIONS: The methylated status of ASC/TMS1 promoter had the potential applicability for clinical evaluation the prognosis of GC. PMID- 26260915 TI - Prognostic value of circulating tumor cells in metastatic breast cancer: a systemic review and meta-analysis. AB - OBJECTIVE: Metastatic breast cancer (MBC) remains the main cause of cancer related death, and the clinical significance and prognostic role of circulating tumor cells (CTCs) in metastatic breast cancer are still controversial. Here, we conducted a meta-analysis to clarify the correlation between CTCs and the clinicopathological features and prognosis of MBC. METHODS: We performed a comprehensive search of Pubmed and the ISI Web of Science through December 2014. Only articles that focused on MBC patients and detected CTCs using the CellSearch system were included. The associations between CTCs and survival rate and clinicopathological parameters, including molecular pattern, metastatic region and treatment response, were evaluated. RESULTS: This meta-analysis included 24 studies (3701 MBC patients), 13 prospective studies and 11 retrospective studies. We found that CTCs were more frequently detected with HER2 + primary tumors (pooled RR = 0.73, 95 % CI = 0.63-0.84). Additionally, higher CTC numbers indicated a worse treatment response (RR = 0.56, 95 % CI = 0.40-0.79), poorer PFS (RR = 0.64, 95 % CI = 0.56-0.73) and poorer OS (RR = 0.69, 95 % CI = 0.64-0.75) in MBC patients. CONCLUSION: Based on these results, we propose that HER2 positivity could be a significant risk factor for the presence of CTCs. Additionally, CTCs have a significant prognostic value for MBC patients. Therefore, CTCs should be continually monitored to guide the treatment of MBC patients, especially those with HER2 + primary tumors. PMID- 26260916 TI - Effect of critical care pharmacist's intervention on medication errors: A systematic review and meta-analysis of observational studies. AB - Pharmacists are integral members of the multidisciplinary team for critically ill patients. Multiple nonrandomized controlled studies have evaluated the outcomes of pharmacist interventions in the intensive care unit (ICU). This systematic review focuses on controlled clinical trials evaluating the effect of pharmacist intervention on medication errors (MEs) in ICU settings. Two independent reviewers searched Medline, Embase, and Cochrane databases. The inclusion criteria were nonrandomized controlled studies that evaluated the effect of pharmacist services vs no intervention on ME rates in ICU settings. Four studies were included in the meta-analysis. Results suggest that pharmacist intervention has no significant contribution to reducing general MEs, although pharmacist intervention may significantly reduce preventable adverse drug events and prescribing errors. This meta-analysis highlights the need for high-quality studies to examine the effect of the critical care pharmacist. PMID- 26260917 TI - Team-Based Biopsychosocial Care in Solid Organ Transplantation. PMID- 26260918 TI - Optical coherence tomography for longitudinal monitoring of vasculature in scars treated with laser fractionation. AB - This study presents the first in vivo longitudinal assessment of scar vasculature in ablative fractional laser treatment using optical coherence tomography (OCT). A method based on OCT speckle decorrelation was developed to visualize and quantify the scar vasculature over the treatment period. Through reliable co location of the imaging field of view across multiple imaging sessions, and compensation for motion artifact, the study was able to track the same scar tissue over a period of several months, and quantify changes in the vasculature area density. The results show incidences of occlusion of individual vessels 3 days after the first treatment. The subsequent responses ~20 weeks after the initial treatment show differences between immature and mature scars. Image analysis showed a distinct decrease (25 +/- 13%, mean +/- standard deviation) and increase (19 +/- 5%) of vasculature area density for the immature and mature scars, respectively. This study establishes the feasibility of OCT imaging for quantitative longitudinal monitoring of vasculature in scar treatment. En face optical coherence tomography vasculature images pre-treatment (top) and ~20 weeks after the first laser treatment (bottom) of a mature burn scar. Arrows mark the same vessel pattern. PMID- 26260919 TI - Erratum: Macholdt, E, Slatkin, M, Pakendorf, B, Stoneking, M. (2015), New insights into the history of the C-14010 lactase persistence variant in Eastern and Southern Africa. Am J Phys Anthropol. 156:661-4. DOI: 10.1002/ajpa.22675. PMID- 26260920 TI - Erratum. PMID- 26260922 TI - Origins of observed reactivity and specificity in the addition of B2Cl4 and analogues to unsaturated compounds. AB - In 1954 Schlesinger and co-workers observed the direct reaction of diboron tetrachloride with simple organic compounds under mild conditions, the 1,2 addition product being formed with either ethylene or acetylene. In the following 25 years a series of addition reactions to simple alkenes, alkynes and dienes was demonstrated. B2F4 was shown to react in similar manner, albeit under more forcing conditions. Crucially, it was demonstrated that the addition to (E)- or (Z)-but-2-ene occurred with cis-stereospecificity. Only sporadic interest was shown in this field thereafter until catalysed addition reactions of diboron reagents were realized. Encouraged by this revival of interest through the discovery of transition-metal and nucleophilic catalysis of diboryl additions, DFT analysis of uncatalysed additions of B2X4 has been carried out and interpreted. This includes the relative reactivity of several B-B reagents with ethene, and that of B2Cl4vs. B2F4 additions, including benzene, naphthalene and C60 as reactants. This allows the analysis of relative reactivity vis-a-vis substitution on boron, and also direct comparison with hydroboration by HBCl2. [4 + 2] Addition of diboron reagents to dienes with B-B cleavage competes with direct [2 + 2] addition, favourably so for B2F4. The computational results demonstrate that the stereospecific addition to isomeric but-2-enes is a rare concerted [2sigmas + 2pis] process. PMID- 26260921 TI - Automated biphasic morphological assessment of hepatitis B-related liver fibrosis using second harmonic generation microscopy. AB - Liver fibrosis assessment by biopsy and conventional staining scores is based on histopathological criteria. Variations in sample preparation and the use of semi quantitative histopathological methods commonly result in discrepancies between medical centers. Thus, minor changes in liver fibrosis might be overlooked in multi-center clinical trials, leading to statistically non-significant data. Here, we developed a computer-assisted, fully automated, staining-free method for hepatitis B-related liver fibrosis assessment. In total, 175 liver biopsies were divided into training (n = 105) and verification (n = 70) cohorts. Collagen was observed using second harmonic generation (SHG) microscopy without prior staining, and hepatocyte morphology was recorded using two-photon excitation fluorescence (TPEF) microscopy. The training cohort was utilized to establish a quantification algorithm. Eleven of 19 computer-recognizable SHG/TPEF microscopic morphological features were significantly correlated with the ISHAK fibrosis stages (P < 0.001). A biphasic scoring method was applied, combining support vector machine and multivariate generalized linear models to assess the early and late stages of fibrosis, respectively, based on these parameters. The verification cohort was used to verify the scoring method, and the area under the receiver operating characteristic curve was >0.82 for liver cirrhosis detection. Since no subjective gradings are needed, interobserver discrepancies could be avoided using this fully automated method. PMID- 26260923 TI - Validation of Flow Cytometry and Magnetic Bead-Based Methods to Enrich CNS Single Cell Suspensions for Quiescent Microglia. AB - Microglia are resident mononuclear phagocytes within the CNS parenchyma that intimately interact with neurons and astrocytes to remodel synapses and extracellular matrix. We briefly review studies elucidating the molecular pathways that underlie microglial surveillance, activation, chemotaxis, and phagocytosis; we additionally place these studies in a clinical context. We describe and validate an inexpensive and simple approach to obtain enriched single cell suspensions of quiescent parenchymal and perivascular microglia from the mouse cerebellum and hypothalamus. Following preparation of regional CNS single cell suspensions, we remove myelin debris, and then perform two serial enrichment steps for cells expressing surface CD11b. Myelin depletion and CD11b enrichment are both accomplished using antigen-specific magnetic beads in an automated cell separation system. Flow cytometry of the resultant suspensions shows a significant enrichment for CD11b(+)/CD45(+) cells (perivascular microglia) and CD11b(+)/CD45(-) cells (parenchymal microglia) compared to starting suspensions. Of note, cells from these enriched suspensions minimally express Aif1 (aka Iba1), suggesting that the enrichment process does not evoke significant microglial activation. However, these cells readily respond to a functional challenge (LPS) with significant changes in the expression of molecules specifically associated with microglia. We conclude that methods employing a combination of magnetic-bead based sorting and flow cytometry produce suspensions highly enriched for microglia that are appropriate for a variety of molecular and cellular assays. PMID- 26260924 TI - Blockade of CD127 Exerts a Dichotomous Clinical Effect in Marmoset Experimental Autoimmune Encephalomyelitis. AB - Non-human primate models of human disease have an important role in the translation of a new scientific finding in lower species into an effective treatment. In this study, we tested a new therapeutic antibody against the IL-7 receptor alpha chain (CD127), which in a C57BL/6 mouse model of experimental autoimmune encephalomyelitis (EAE) ameliorates disease, demonstrating an important pathogenic function of IL-7. We observed that while the treatment was effective in 100 % of the mice, it was only partially effective in the EAE model in common marmosets (Callithrix jacchus), a small-bodied Neotropical primate. EAE was induced in seven female marmoset twins and treatment with the anti-CD127 mAb or PBS as control was started 21 days after immunization followed by weekly intravenous administration. The anti-CD127 mAb caused functional blockade of IL-7 signaling through its receptor as shown by reduced phosphorylation of STAT5 in lymphocytes upon stimulation with IL-7. Group-wise analysis showed no significant effects on the clinical course and neuropathology. However, paired twin analysis revealed a delayed disease onset in three twins, which were high responders to the immunization. In addition, we observed markedly opposite effects of the antibody on pathological changes in the spinal cord in high versus low responder twins. In conclusion, promising clinical effect of CD127 blockade observed in a standard inbred/SPF mouse EAE model could only be partially replicated in an outbred/non-SPF non-human primate EAE model. Only in high responders to the immunization we found a positive response to the treatment. The mechanism underpinning this dichotomous response will be discussed. PMID- 26260926 TI - The effects of ageing on self-reported aggression measures are partly explained by response bias. AB - BACKGROUND: Recent studies have suggested that the age-personality relationship may be partly explained by age-related changes in response bias. In the present study, we analysed how age affected social desirability and acquiescence, and how this effect impacted the age-aggression relationship. METHOD: We used the Indirect-Direct Aggression Questionnaire, which provides response bias and physical, verbal and indirect aggression scores independently of each other. We applied this test to a sample of 616 individuals aged between 18 and 96 (M = 49.24, SD = 24.81) and analysed the relationships between age and aggression measures with and without response bias. RESULTS: We found that social desirability and acquiescence increased by between one and two standard deviations between adulthood and old age. This affected the age-aggression relationship for all aggression scales and, especially for verbal and indirect aggression, whose relationships with age decreased from r = -.192 and r = -.309 to r = .012 and r = -.159, respectively, when response biases were controlled. CONCLUSIONS: When response bias and, in particular social desirability, are not controlled, elderly people tend to show aggression scores that are considerably lower than their true aggression levels. PMID- 26260925 TI - Enhanced molecular mobility of ordinarily structured regions drives polyglutamine disease. AB - Polyglutamine expansion is a hallmark of nine neurodegenerative diseases, with protein aggregation intrinsically linked to disease progression. Although polyglutamine expansion accelerates protein aggregation, the misfolding process is frequently instigated by flanking domains. For example, polyglutamine expansion in ataxin-3 allosterically triggers the aggregation of the catalytic Josephin domain. The molecular mechanism that underpins this allosteric aggregation trigger remains to be determined. Here, we establish that polyglutamine expansion increases the molecular mobility of two juxtaposed helices critical to ataxin-3 deubiquitinase activity. Within one of these helices, we identified a highly amyloidogenic sequence motif that instigates aggregation and forms the core of the growing fibril. Critically, by mutating residues within this key region, we decrease local structural fluctuations to slow ataxin-3 aggregation. This provides significant insight, down to the molecular level, into how polyglutamine expansion drives aggregation and explains the positive correlation between polyglutamine tract length, protein aggregation, and disease severity. PMID- 26260927 TI - Cognitive decline before the age of 50 can be detected with sensitive cognitive measures. AB - BACKGROUND: To define the profile of age-related differences in cognition in healthy middle-aged adults in order to identify the most sensitive measures of early cognitive decline. To study whether these differences precede cognitive decline in the elderly. METHOD: 141 cognitively normal participants (101 middle aged adults with age 40-50±2; and 40 elderly individuals with age 65±2) were assessed with a comprehensive neuropsychological protocol covering processing speed, attention, executive functions, verbal and visual episodic memory, procedural memory, visuoconstructive, visuoperceptive and visuospatial functions, and language. RESULTS: Age-related differences were detected before the age of 50 in cognitive reaction time, executive control, initial learning in verbal episodic memory, complex visuoconstructive and visuospatial functions, and lexical access. These differences preceded more extensive cognitive decline present at the age of 65. CONCLUSIONS: Our findings suggest subtle executive dysfunction before the age of 50, together with slowing in processing speed later on in the transition to old age. This profile could be explained by changes in the frontal lobe and its connections, starting at middle age. These findings, together with future research, may be important for the diagnosis, prognosis, and prevention of pathological aging at a very early level. PMID- 26260928 TI - Prevalence and functions of non-suicidal self-injury in Spanish adolescents. AB - BACKGROUND: This study examined the prevalence, characteristics and functions of Non-suicidal Self-injury (NSSI) among Spanish adolescents. METHOD: The sample consisted of 1,864 adolescents aged between 12 and 19 years (Mean Age = 15.32, SD = 1.97, 51.45% girls). The participants completed a modified version of the self report scale Functional Assessment of Self-Mutilation (FASM; Lloyd, Kelley, & Hope, 1997) to assess rates and methods of NSSI used during the last 12 months. They also indicated the functions of NSSI. RESULTS: NSSI behaviors are common among Spanish adolescents. More than half of the sample showed such behavior in the past year, and 32.2% had carried out severe NSSI behaviors. The functions of NSSI were examined by using confirmatory factor analyses. Results supported a hierarchical model consisting of two second-order factors: automatic reinforcement, which explained both positive and negative automatic reinforcement, and social reinforcement, which explained both positive and negative social reinforcement. CONCLUSIONS: These dimensions are critical to understand the factors that maintain NSSI behavior and have implications for treatments. PMID- 26260929 TI - The influence of cochlear implants on behaviour problems in deaf children. AB - BACKGROUND: This study seeks to analyse the relationship between behaviour problems in deaf children and their auditory and communication development subsequent to cochlear implantation and to examine the incidence of these problems in comparison to their hearing peers. METHOD: This study uses an ex post facto prospective design with a sample of 208 Spanish children, of whom 104 were deaf subjects with cochlear implants. The first objective assesses the relationships between behaviour problems, auditory integration, and social and communication skills in the group of deaf children. The second compares the frequency and intensity of behaviour problems of the group of deaf children with their hearing peers. RESULTS: The correlation analysis showed a significant association between the internal index of behaviour problems and auditory integration and communication skills, such that deaf children with greater auditory and communication development had no behaviour problems. When comparing behaviour problems in deaf children versus their hearing peers, behavioural disturbances are significantly more frequent in the former. CONCLUSIONS: According to these findings, cochlear implants may not guarantee adequate auditory and communicative development that would normalise the behaviour of deaf children. PMID- 26260930 TI - Neurophysiological indicators of emotional processing in youth psychopathy. AB - BACKGROUND: Research with psychopathic samples using the technique of evoked potentials is rather limited and almost exclusively concerned with the study of the P300 component; no studies have been found (to date) that assess shorter wave latencies. This research focuses on the emotional and attentional processes in young people with psychopathic characteristics, using the evoked potential technique in short-wave latency (N100). METHOD: The experimental group consisted of 22 subjects; all of them met the psychopathic criteria of the Antisocial Process Screening Device (APSD) and the Psychopathy Checklist: Youth Version (PCL: YV). The control sample consisted of 25 subjects, all of them scoring less than 15 points in APSD. RESULTS: In the experimental group, the mechanisms responsible for processing the pleasant stimulation responded earlier and with more intensity (on the N100); premium positivity bias on negativity. CONCLUSIONS: This emotional deficit found in the literature on psychopathy in adults is also found in young people. PMID- 26260931 TI - Feelings of ease and attitudes toward healthy foods. AB - BACKGROUND: The successful impact of health campaigns often depends on the extent to which interventions are effective in changing attitudes. The goal of the present research was to examine to what extent the ease adolescents experience in generating thoughts can influence persuasion in the domain of a health-relevant topic. METHOD: Participants were asked to generate either positive or negative thoughts about the Mediterranean diet. The spontaneous feeling of ease with which participants generated those thoughts was assessed for each participant. The impact of these two independent variables on attitudes toward the Mediterranean diet was examined. RESULTS: Participants who reported relatively higher (vs. lower) subjective ease experiences in the thought-listing task showed a greater effect of thought direction on attitudes toward the diet. CONCLUSION: This study demonstrates the importance of considering not only the thoughts people have with regard to health but also the subjective experiences and metacognitive feelings associated with those thoughts. PMID- 26260932 TI - The eudaimonic component of satisfaction with life and psychological well-being in Spanish cultures. AB - BACKGROUND: In the study of well-being there are two partially overlapping traditions that have been developed in parallel. Subjective well-being (SWB) has been associated with the hedonistic approach of well-being, and psychological well-being (PWB) with the eudaimonistic one. However, satisfaction with life, the most common SWB indicator, is not strictly a hedonic concept and contains many eudaimonic components. The objective of this research is to examine whether a Eudaimonic Well-being G-Factor of Satisfaction with Life (SWLS) and Psychological Well-being Scales (PWBS) emerges. METHOD: 400 people from the general population of Colombia (Study 1) and 401 from Spain (Study 2), recruited via advertisement, voluntarily participated and filled in a booklet containing, in order of appearance, the PWBS and the SWLS. RESULTS: According to our hypothesis, parallel analysis, eigenvalues, scree plot graphs and exploratory factor analysis (Study 1) suggested the existence of a one-factor structure. Confirmatory factor analysis (Study 2) indicated that this one-factor model provided excellent data fit. Results of a multi-group confirmatory factor analysis confirmed cross cultural factor invariance. CONCLUSIONS: These results question the view that the satisfaction with life indicator is uniquely hedonic and point to the need for a greater integration between hedonic and eudaimonic traditions. PMID- 26260933 TI - Obsessive-compulsive disorder and its relationship with disgust vulnerability and conscientiousness. AB - BACKGROUND: The aim of this study was to analyze the relationship between Obsessive-Compulsive Disorder (OCD) symptoms, disgust vulnerability, and the Five Factor Model (FFM) of personality. METHOD: The sample consisted of 100 adult patients with OCD as a primary diagnosis and 246 with other anxiety disorders (OADs), who responded to OCD, disgust vulnerability, anxiety, depression and personality questionnaires. To perform parametric statistical calculations, all questionnaire scores were transformed from raw ordinal-scale scores to Rasch measures, with interval properties. RESULTS: OCD patients scored significantly higher than OAD patients on DPSS-R Disgust Sensitivity and DPSS-R Disgust Propensity, with a large effect size observed on Disgust Propensity. Furthermore, strong correlations were observed between DPSS-R Propensity to Disgust model scores and DOCS Contamination model scores. Finally, NEO FFI Conscientiousness trait was significantly higher in OCD patients. PMID- 26260934 TI - Adaptation and validation in Spanish of the Group Environment Questionnaire (GEQ) with professional football players. AB - BACKGROUND: This investigation presents two studies with the goal of adapting and validating a short version of the Group Environment Questionnaire in the Spanish sport context with professional players. METHOD: Study 1 used a sample of 377 male soccer players aged between 18 and 39 years ( M = 24.51, SD = 3.73), in a preliminary study using exploratory factor analysis. Study 2 used a sample of 604 professional male and female athletes, ages between 15 and 38 years ( M = 24.34, SD = 4.03). The data analyzed were collected at three moments of the season. For each measurement, we developed seven first- and second-order structures that were analyzed with confirmatory factor analysis. RESULTS: Study 1 indicated appropriate factorial validity (> .60) and internal consistency (> .70), with only Item 3 presenting a low factor loading (.11), so its drafting was modified in the next study. Study 2 revealed that the Spanish version of the GEQ has high levels of internal consistency (> .70) and acceptable fit index values in its original four first-order factor structure in all three measurements ( chi2/df = 4.39, CFI = .95, IFI = .95, RMSEA = .07, SRMR = .04, AIC = 271.09). Discriminant validity (from r = .45 to r = .72) and concurrent validity (from r = .21 to r = .60) also presented appropriate values. Lastly, we conducted analysis of invariance, confirming that the models established in the different measurements were invariant. CONCLUSIONS: The short 12-item adaptation of the GEQ to Spanish is a valid and reliable instrument to measure team cohesion in professional male and female soccer players. PMID- 26260935 TI - Psychometric properties of the Somatic Complaints Scale in Spanish children and adults. AB - BACKGROUND: The aim of this study was to analyse the psychometric properties of the Somatic Complaints List (SCL) in Spanish child and adult populations. This instrument assesses the frequency with which people experience and feel pain such as stomach ache and headache, among others. It has been validated in different countries and languages (Dutch, English, and Persian), showing adequate psychometric properties. Nevertheless, it has never been validated in a Spanish context. METHOD: For the adaptation and validation, we used two different samples: 1423 children, age ranging from 8 to 12 years old, selected from 12 primary and secondary schools at 7 locations in the Valencian Community, Spain (age = 9.11 years, SD = 1.27; 52.4% female); and 940 adults, age ranging from 18 to 56 years old (age = 32.3 years, SD = 11.62; 64% female). RESULTS: The Spanish adaptation of the SLC showed adequate levels of reliability and validity. CONCLUSIONS: The empirical evidence seems sufficient to justify using this diagnostic tool with Spanish children and adults. PMID- 26260936 TI - Associative learning with and without perceptual awareness. AB - BACKGROUND: The relationship between awareness and associative learning is a key controversial issue that remains to be elucidated. An experiment was designed to assess associative learning with and without perceptual awareness. METHOD: Participants received repeated trials of two compatible stimuli sequences (S1A -> S2A and S1B -> S2B ), where S1 was a masked stimulus, and S2 an imperative stimulus for a reaction time (RT) task. After the acquisition phase, some probe trials of incompatible stimuli sequences (S1A -> S2B and S1B -> S2A ) were inserted among the compatible sequence trials during two testing sessions. Subsequently, subjects were classified as perceptually aware or perceptually unaware by means of a forced-choice identification task that was administered at the beginning and end of the experiment. RESULTS: The results showed perceptually unaware participants responded faster to compatible than to incompatible stimuli sequences. However, no priming effect was observed in aware participants. CONCLUSIONS: These results are discussed in terms of an S-R associative mechanism and provide strong evidence of unconscious associative learning. PMID- 26260937 TI - Guidelines for reporting evaluations based on observational methodology. AB - BACKGROUND: Observational methodology is one of the most suitable research designs for evaluating fidelity of implementation, especially in complex interventions. However, the conduct and reporting of observational studies is hampered by the absence of specific guidelines, such as those that exist for other evaluation designs. This lack of specific guidance poses a threat to the quality and transparency of these studies and also constitutes a considerable publication hurdle. The aim of this study thus was to draw up a set of proposed guidelines for reporting evaluations based on observational methodology. METHOD: The guidelines were developed by triangulating three sources of information: observational studies performed in different fields by experts in observational methodology, reporting guidelines for general studies and studies with similar designs to observational studies, and proposals from experts in observational methodology at scientific meetings. RESULTS: We produced a list of guidelines grouped into three domains: intervention and expected outcomes, methods, and results. CONCLUSIONS: The result is a useful, carefully crafted set of simple guidelines for conducting and reporting observational studies in the field of program evaluation. PMID- 26260938 TI - Interpretation of the p value: A national survey study in academic psychologists from Spain. AB - BACKGROUND: Incorrect interpretations of p values affect professionals’ decisions and jeopardize the quality of psychological interventions and the accumulation of valid scientific knowledge. This study analyzes the errors made by Spanish academic psychologists in interpreting p values. METHOD: We surveyed academic psychologists about their interpretations of p values. The sample is composed of 418 academic psychologists from Spanish public universities. The mean number of years working as a university professor is 14.16 (SD = 9.39). RESULTS: Our findings suggest that many academic psychologists do not know how to correctly interpret p values. The inverse probability fallacy presents the greatest comprehension problems. Methodology instructors also interpret the significance of the p value erroneously. CONCLUSIONS: These results highlight the importance of the statistical re-education of professors. PMID- 26260939 TI - Partial scalar invariance and observed differences across gender in a reasoning test battery. AB - BACKGROUND: The substantive basis of the Reasoning Test Battery (BPR) is the theory of the hierarchical organization of cognitive abilities and therefore, it combines a general cognitive factor and specific factors associated with abstract, numerical, verbal, practical, spatial and mechanical reasoning. The battery has three forms, covering an age range from 9 to 22 years. METHOD: The present study analyzes the internal structure of the Basque version of the battery using exploratory and confirmatory factor analyses. Factorial invariance studies across gender were performed and partial differences observed were analyzed in a sample of 1,923 students. RESULT: The results concluded: (a) the presence of one general reasoning factor in each of the forms, (b) partial scalar invariance across gender affecting mechanical reasoning and numerical reasoning, (c) no differences in the general reasoning factor, and (d) negligible observed differences in partial scales. CONCLUSIONS: Tests for measurement invariance indicate differences in factor intercepts, cautioning that comparisons of observed g scores across gender are not appropriate. PMID- 26260941 TI - Intracranial Aneurysm Pathophysiology: To Bleed, or not To Bleed, That Is the Question. PMID- 26260940 TI - Influence of Hormone Receptor Status on Spinal Metastatic Lesions in Patients with Breast Cancer. AB - OBJECTIVE: Bony metastasis predominantly affects the spinal column and has been commonly associated in patients with breast cancer. There are two types of lesions that can occur with spine cancer-osteolytic or osteoblastic. Some patients may have mixed lesions, which include lytic and blastic in one vertebra or lytic and blastic in different vertebrae. Previous studies have shown that patients with breast cancer have an increased likelihood for development of lytic spinal metastases. METHODS: A retrospective chart review was conducted to more closely examine the association between hormone receptor status and spinal lesion type. A total of 195 patients were initially identified through the City of Hope Cancer Registry. Of the 195, only 153 patients had hormone receptor marker status available. Associations between spinal lesion and hormone receptor status were evaluated using chi(2) tests with alpha = 0.05 significance level. In a secondary analysis, the Oncomine Platform was used, which integrated The Cancer Genome Atlas (TCGA) datasets, to identify osteogenic genes that may be relevant to invasive breast cancers. RESULTS: Contrary to previous studies, our findings revealed progesterone receptor positive (PR+) patients were significantly more likely to present with blastic than lytic or mixed lesions. Furthermore, using TCGA analysis, COL1A1 and COL1A2 were found to be up-regulated, which could provide a molecular explanation for the development of blastic metastases. CONCLUSIONS: By integrating clinical and bioinformatic techniques, this study provides a novel discovery of the relationship between blastic and PR + breast cancers, which may have important implications for diagnostic strategies concerning vertebral metastases. PMID- 26260942 TI - Phospholipase Depsilon enhances Braasca napus growth and seed production in response to nitrogen availability. AB - Phospholipase D (PLD), which hydrolyses phospholipids to produce phosphatidic acid, has been implicated in plant response to macronutrient availability in Arabidopsis. This study investigated the effect of increased PLDepsilon expression on nitrogen utilization in Brassica napus to explore the application of PLDepsilon manipulation to crop improvement. In addition, changes in membrane lipid species in response to nitrogen availability were determined in the oil seed crop. Multiple PLDepsilon over expression (PLDepsilon-OE) lines displayed enhanced biomass accumulation under nitrogen-deficient and nitrogen-replete conditions. PLDepsilon-OE plants in the field produced more seeds than wild-type plants but have no impact on seed oil content. Compared with wild-type plants, PLDepsilon-OE plants were enhanced in nitrate transporter expression, uptake and reduction, whereas the activity of nitrite reductase was higher under nitrogen depleted, but not at nitrogen-replete conditions. The level of nitrogen altered membrane glycerolipid metabolism, with greater impacts on young than mature leaves. The data indicate increased expression of PLDepsilon has the potential to improve crop plant growth and production under nitrogen-depleted and nitrogen replete conditions. PMID- 26260943 TI - Leaves of Persimmon (Diospyros kaki Thunb.) Ameliorate N-Methyl-N-nitrosourea (MNU)-Induced Retinal Degeneration in Mice. AB - The purpose of the study was to investigate the protective effects of the ethanol extract of Diospyros kaki (EEDK) persimmon leaves to study N-methyl-N-nitrosourea (MNU)-induced retinal degeneration in mice. EEDK was orally administered after MNU injection. Retinal layer thicknesses were significantly increased in the EEDK treated group compared with the MNU-treated group. The outer nuclear layer was preserved in the retinas of EEDK-treated mice. Moreover, EEDK treatment reduced the MNU-dependent up-regulation of glial fibrillary acidic protein (GFAP) and nestin expression in Muller and astrocyte cells. EEDK treatment also inhibited MNU-dependent down-regulation of rhodopsin expression. Quercetin exposure significantly attenuated the negative effects of H2O2 in R28 cells, suggesting that quercetin can act in an antioxidative capacity. Thus, EEDK may be considered as an agent for treating or preventing degenerative retinal diseases, such as retinitis pigmentosa and age-related macular degeneration. PMID- 26260945 TI - Phylogenetically diverse AM fungi from Ecuador strongly improve seedling growth of native potential crop trees. AB - In many deforested regions of the tropics, afforestation with native tree species could valorize a growing reservoir of degraded, previously overused and abandoned land. The inoculation of tropical tree seedlings with arbuscular mycorrhizal fungi (AM fungi) can improve tree growth and viability, but efficiency may depend on plant and AM fungal genotype. To study such effects, seven phylogenetically diverse AM fungi, native to Ecuador, from seven genera and a non-native AM fungus (Rhizophagus irregularis DAOM197198) were used to inoculate the tropical potential crop tree (PCT) species Handroanthus chrysanthus (synonym Tabebuia chrysantha), Cedrela montana, and Heliocarpus americanus. Twenty-four plant fungus combinations were studied in five different fertilization and AMF inoculation treatments. Numerous plant growth parameters and mycorrhizal root colonization were assessed. The inoculation with any of the tested AM fungi improved seedling growth significantly and in most cases reduced plant mortality. Plants produced up to threefold higher biomass, when compared to the standard nursery practice. AM fungal inoculation alone or in combination with low fertilization both outperformed full fertilization in terms of plant growth promotion. Interestingly, root colonization levels for individual fungi strongly depended on the host tree species, but surprisingly the colonization strength did not correlate with plant growth promotion. The combination of AM fungal inoculation with a low dosage of slow release fertilizer improved PCT seedling performance strongest, but also AM fungal treatments without any fertilization were highly efficient. The AM fungi tested are promising candidates to improve management practices in tropical tree seedling production. PMID- 26260946 TI - Mean platelet volume evaluation in patients with sarcoidosis: methodological drawbacks. PMID- 26260947 TI - Gua Lou Gui Zhi decoction attenuates post-stroke spasticity via the modulation of GABAB receptors. AB - The aim of the present study was to investigate the mechanisms underlying the neuroprotective and antispastic effects of Gua Lou Gui Zhi decoction (GLGZD) in a rat model of middle cerebral artery occlusion (MCAO). The MCAO rats were treated with GLGZD (14.3 g/kg body weight) once a day for a period of seven days. Neurological deficit scores and screen tests were analyzed every other day. Following treatment with GLGZD for 7 days, the ischemic infarct volume of the rat brains was measured using 2,3,5-triphenyl tetrazolium chloride staining. Reverse transcription-polymerase chain reaction was performed in order to determine the mRNA expression levels of gamma-amino butyric acid B (gamma-GABAB) receptor (R) in the cortical infarct region. Furthermore, the protein expression levels of GABAB R were detected in the cortical infarct region by western blot analysis. Following 7 days, treatment with GLGZD significantly ameliorated the neurological defects and cerebral infarction in the MCAO rats. In addition, treatment with GLGZD ameliorated motor performance in the MCAO rats, as determined by screen tests. Furthermore, GLGZD was able to upregulate the mRNA and protein expression levels of GABAB1 R and GABAB2 R in the ischemic cerebral cortex. The results of the present study suggested that GLGZD may exert neuroprotective and antispastic effects in a cerebral ischemia model, through upregulating the expression of GABAB R. PMID- 26260948 TI - Mental health and alcohol problems among Estonian cleanup workers 24 years after the Chernobyl accident. AB - PURPOSE: To study the long-term mental health consequences of the 1986 Chernobyl nuclear accident among cleanup workers from Estonia. METHODS: In 2010, 614 Estonian Chernobyl cleanup workers and 706 geographically and age-matched population-based controls completed a mail survey that included self-rated health, the Posttraumatic Stress Disorder Checklist (PCL), alcohol symptoms (AUDIT), and scales measuring depressive, anxiety, agoraphobia, fatigue, insomnia, and somatization symptoms. Respondents were dichotomized into high (top quartile) and low symptom groups on each measure. RESULTS: Logistic regression analysis detected significant differences between cleanup workers and controls on all measures even after adjustment for ethnicity, education, marital status, and employment status. The strongest difference was found for somatization, with cleanup workers being three times more likely than controls to score in the top quartile (OR = 3.28, 95% CI 2.39-4.52), whereas for alcohol problems the difference was half as large (OR = 1.52, 95% CI 1.16-1.99). Among cleanup workers, arrival at Chernobyl in 1986 (vs. later) was associated with sleep problems, somatization, and symptoms of agoraphobia. CONCLUSION: The toll of cleanup work was evident 24 years after the Chernobyl accident among Estonian cleanup workers indicating the need for focused mental health interventions. PMID- 26260949 TI - Mediated moderation of the relation between maternal and adolescent depressive symptoms: role of adolescent physical health. AB - BACKGROUND: To examine the mediating effect of family functioning on the relation between maternal and adolescent depressive symptoms and determine whether the magnitude of the mediating effect is different for adolescents with and without chronic physical health conditions. METHODS: Data come from the National Longitudinal Survey of Children and Youth. A representative survey of 11,813 adolescents and their mothers was included. Maternal and adolescent depressive symptoms were measured using the 12-item Center for Epidemiological Studies Depression Scale. Family functioning was measured using the McMaster Family Assessment Device. Multilevel multiple-group path analysis was used to examine potential mediating and moderating effects. RESULTS: Family functioning measured when adolescents were 14-15 years mediated the relation between maternal depressive symptoms (measured at 10-13 years) and adolescent depressive symptoms (measured at 16-19 years) for both adolescents with [alphabeta = 0.02 (0.02, 0.03)] and without chronic health conditions [alphabeta = 0.01 (0.00, 0.01)]. These findings provided evidence to suggest mediated moderation, Deltaalphabeta = 0.02 (0.01, 0.03), that is, the mediating effect of family functioning was significantly larger for adolescents with chronic health conditions. CONCLUSIONS: The mediating effect of family functioning in the relation between maternal and adolescent depressive symptoms is larger for adolescents with chronic health conditions. Within the framework of family-centered care, maternal depressive symptoms and family functioning are suitable targets for preventive intervention for adolescents with chronic health conditions. PMID- 26260950 TI - Prevalence of substance use disorders in psychiatric patients: a nationwide Danish population-based study. AB - PURPOSE: The present study established the national prevalence of substance use disorders (SUDs) among Danish psychiatric patients. Furthermore, patients with SUDs and those without SUDs were compared on a range of socio-demographic, clinical, and treatment characteristics. METHODS: Data were obtained from several Danish population-based registers. The study population was defined as all individuals with incidents of schizophrenia, schizotypal disorder, other psychoses, bipolar disorder, depression, anxiety, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and personality disorders since 1969. The prevalence of SUDs was examined for the following psychoactive substances: alcohol, opioids, cannabis, sedatives, cocaine, psycho-stimulants and hallucinogens. RESULTS: A total of 463,003 patients were included in the analysis. The prevalence of any lifetime SUD was: 37 % for schizophrenia, 35 % for schizotypal disorder, 28 % for other psychoses, 32 % for bipolar disorder, 25 % for depression, 25 % for anxiety, 11 % for OCD, 17% for PTSD, and 46 % for personality disorders. Alcohol use disorder was the most dominating SUD in every psychiatric category (25 % of all included patients). Patients with SUDs were more often men, had fewer years of formal education, more often received disability pension and died due to unnatural causes. CONCLUSIONS: The study was the most comprehensive of its kind so far to estimate the prevalence of SUDs in an unselected population-based cohort, and it revealed remarkably high prevalence among the psychiatric patients. The results should encourage continuous focus on possible comorbidity of psychiatric patients, as well as specialised and integrated treatment along with increased support of patients with comorbid disorders. PMID- 26260952 TI - Perineural growth of benign cutaneous sweat gland tumors: a hitherto unrecognized phenomenon unassociated with malignancy. AB - BACKGROUND: Cutaneous intraneural reactive epithelial proliferations mimicking malignancy include epithelial sheath neuroma, re-excision perineural invasion and reactive neuroepithelial aggregates. Nevertheless, intraneural growth of benign sweat gland tumors has not been reported before. AIMS: To report a predominantly intraneural proliferation of morphologically bland sweat gland tumors, describe their clinicopathological features and correlate them with survival. RESULTS: We analyzed a spiradenoma and a hidradenoma with a prominent intraneural growth, occurring on the back of the 19-year-old woman and on the arm of the 53-year-old woman. Both lesions presented as a painful and slightly raised papule. After complete excision, an uneventful clinical course was observed during the follow up period of 52 and 54 months. Pathologically, the most striking feature was an almost exclusive intraneural growth within the peripheral nerves of the deep dermis and subcutis. CONCLUSION: We report for the first time the predominantly intraneural growth of benign sweat gland tumors. Although their histogenesis is unknown, perineural displacement due to previous surgery or trauma, as well as development from intraneural embryological epithelial remnants remains possibilities. Long-term follow-up of our patients suggests that intraneural growth of otherwise bland sweat gland tumors does not signify malignancy. Complete excision appears to be sufficient treatment procedure. PMID- 26260951 TI - Drug use and service utilization among Hispanics in the United States. AB - PURPOSE: To examine illicit drug use and service utilization patterns of US-born and foreign-born Hispanics in the United States. METHODS: Hispanic respondents 18 years and older in the NESARC were categorized as being of Mexican (n = 3,556), Puerto Rican (n = 785), Cuban (n = 346), Central American (n = 513), or South American (n = 381) origin. We examined lifetime prevalence of drug use and substance abuse treatment utilization patterns for US-born and Hispanic immigrants across subgroups. RESULTS: Lifetime prevalence of drug use was greater among US-born Hispanics than Hispanic immigrants after controlling for age, gender, income, education, urbanicity, parental history of drug use problems and lifetime DSM-IV mood/anxiety disorders. Both US-born and immigrant Hispanic drug users were less likely than non-Hispanic white drug users to have utilized any form of substance abuse treatment (US-born AOR = 0.89, immigrant AOR = 0.64) and more likely to have utilized family or social services (US-born AOR = 1.17, immigrant AOR = 1.19). Compared to US-born Hispanic drug users, Hispanic immigrant drug users were less likely to have used any form of substance abuse treatment (AOR = 0.81) and were more likely to have utilized family or social services (AOR = 1.22). CONCLUSION: Strategies to increase engagement and retention of Hispanic drug users in substance abuse treatment include increasing access to linguistically and culturally competent programs that address unmet family and social needs. Further studies examining differences in drug use and service utilization patterns within Hispanic subgroups are needed. PMID- 26260953 TI - Targeting glucocerebrosidase: Reduced enzymatic activity and Parkinson's disease. PMID- 26260954 TI - Bone repair of critical size defects treated with autogenic, allogenic, or xenogenic bone grafts alone or in combination with rhBMP-2. AB - OBJECTIVE: To evaluate the bone repair of critical size defects treated with autogenic, allogenic, or xenogenic bone grafts alone or in combination with rhBMP 2. MATERIAL AND METHODS: In 112 rats, a critical bone defect of 5 mm bilaterally in the calvaria was made and filled with different bone grafts alone or combined with rhBMP-2: group autograft (AuG); group allograft (AlG); group xenograft (XeG); group AuG/BMP-2 (autograft and 5 MUg rhBMP-2); group AlG/BMP-2 (allograft and 5 MUg rhBMP-2); group XeG/BMP-2 (xenograft and 5 MUg rhBMP-2); group BMP-2 (5 MUg rhBMP-2); and control group, filled only with blood coagulum. After a period of 4 or 6 weeks, the animals were euthanized. Histological and histometric analyses were performed for new bone formation (NB), as well as the immunohistochemical detection of tartrate-resistant acid phosphatase (TRAP), and zymographic analysis (MMP) of type 2 and 9. RESULTS: Histological analysis showed the bone healing process was faster and favorable in AuG and AuG/BMP-2. In both periods, the grafted groups (AuG, XeG and AlG) had a greater volume of NB than the control group, which was even greater when combined with rhBMP-2. The XeG group showed a higher number of TRAP-positive multinucleated osteoclasts, and enzymatic activity revealed different levels of proMMP-2, MMP-2, and MMP-9 (6 weeks). CONCLUSION: The different types of grafts increased bone formation, mainly associated with rhBMP-2, enhancing and accelerating the repair process. These groups had higher enzymatic indices than the control group especially with XeG, which also showed higher TRAP-positive multinucleated cells similar to osteoclasts, suggesting a remodeling process. PMID- 26260955 TI - High spectral purity Kerr frequency comb radio frequency photonic oscillator. AB - Femtosecond laser-based generation of radio frequency signals has produced astonishing improvements in achievable spectral purity, one of the basic features characterizing the performance of an radio frequency oscillator. Kerr frequency combs hold promise for transforming these lab-scale oscillators to chip-scale level. In this work we demonstrate a miniature 10 GHz radio frequency photonic oscillator characterized with phase noise better than -60 dBc Hz(-1) at 10 Hz, 90 dBc Hz(-1) at 100 Hz and -170 dBc Hz(-1) at 10 MHz. The frequency stability of this device, as represented by Allan deviation measurements, is at the level of 10(-10) at 1-100 s integration time-orders of magnitude better than existing radio frequency photonic devices of similar size, weight and power consumption. PMID- 26260956 TI - Proximal femur giant solitary plasmacytoma of bone: lessons learnt. PMID- 26260957 TI - Carcinoma in accessory axillary breast. AB - We present a rare case of carcinoma developing in an accessory breast. The patient presented with a progressive lump in her right axilla for 1 year. On examination, there was a well-developed nipple areola complex in the right axilla overlying a hard, fixed 5 * 3 cm lump. On investigation, core biopsy revealed poorly differentiated carcinoma of the breast. Mammography also revealed features of a malignant lesion with skin and muscle infiltration. Neoadjuvant chemotherapy was administered followed by modified radical mastectomy after three cycles. Immunohistochemistry study showed positive status of oestrogen and progesterone receptors, and negative HER-2 neu. Three more cycles of chemotherapy along with 50 Gy radiotherapy were given in an adjuvant setting followed by hormone therapy. PMID- 26260959 TI - Benign thyroid nodules with RAS mutation grow faster. AB - CONTEXT: The management of a benign thyroid nodule includes follow-up until its size requires a surgical or alternative treatment. To date, it is difficult or impossible to predict the size changes of a benign nodule in a given patient because no specific growth parameters exist. RAS mutations have been described in thyroid adenomas and hyperplastic benign nodules. OBJECTIVE: The aim of this study was to establish whether the volume changes of benign nodules are associated with the presence of RAS mutation. PATIENTS AND METHODS: Genomic DNA obtained by fine-needle aspiration of 78 thyroid nodules with benign cytology was analysed by pyrosequencing for the presence of NRAS(61) and KRAS(13) mutations. Ultrasonographic features were obtained. The volume of nodules at baseline and their changes after a mean follow-up of 25 months were evaluated according to the presence of RAS mutation. RESULTS: A RAS mutation was found in 24 thyroid aspirates (30.8%, 8 NRAS(61) and 16 KRAS(13) ). RAS mutation was not associated with ultrasonographic features, but was significantly associated with a larger size at baseline (P = 0.017). After a 25-month mean follow-up, RAS mutation positive nodules displayed faster growth (RAS mutation-positive vs RAS mutation negative % annual growth 27.6% +/-32.2% vs 1.0% +/-17.0%, P < 0.001). CONCLUSIONS: Benign thyroid nodules bearing RAS mutation grow more rapidly than those with wild-type RAS. Searching for RAS mutations in thyroid nodules with benign cytology might be useful to the clinician in choosing a more appropriate and timely surgical management. PMID- 26260958 TI - Neural Stem Cells Secreting Anti-HER2 Antibody Improve Survival in a Preclinical Model of HER2 Overexpressing Breast Cancer Brain Metastases. AB - The treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer has been revolutionized by trastuzumab. However, longer survival of these patients now predisposes them to forming HER2 positive brain metastases, as the therapeutic antibodies cannot cross the blood brain barrier. The current oncologic repertoire does not offer a rational, nontoxic targeted therapy for brain metastases. In this study, we used an established human neural stem cell line, HB1.F3 NSCs and generated a stable pool of cells secreting a high amount of functional full-length anti-HER2 antibody, equivalent to trastuzumab. Anti-HER2Ab secreted by the NSCs (HER2Ab-NSCs) specifically binds to HER2 overexpressing human breast cancer cells and inhibits PI3K-Akt signaling. This translates to HER2Ab-NSC inhibition of breast cancer cell growth in vitro. Preclinical in vivo experiments using HER2Ab overexpressing NSCs in a breast cancer brain metastases (BCBM) mouse model demonstrate that intracranial injection of HER2Ab-NSCs significantly improves survival. In effect, these NSCs provide tumor localized production of HER2Ab, minimizing any potential off-target side effects. Our results establish HER2Ab-NSCs as a novel, nontoxic, and rational therapeutic approach for the successful treatment of HER2 overexpressing BCBM, which now warrants further preclinical and clinical investigation. PMID- 26260960 TI - Letter from the Editor. PMID- 26260963 TI - Oxidative inactivation of NiFeSe hydrogenase. AB - We propose a resolution to the paradox that spectroscopic studies of NiFeSe hydrogenase have not revealed any major signal attributable to Ni(III) states formed upon reaction with O2, despite the fact that two inactive states are formed upon either aerobic or anaerobic oxidation. PMID- 26260962 TI - Epilepsy and innate immune system: A possible immunogenic predisposition and related therapeutic implications. AB - Recent experimental studies and pathological analyses of patient brain tissue samples with refractory epilepsy suggest that inflammatory processes and neuroinflammation plays a key-role in the etiopathology of epilepsy and convulsive disorders. These inflammatory processes lead to the secretion of pro inflammatory cytokines responsible for blood-brain-barrier disruption and involvement of resident immune cells in the inflammation pathway, occurring within the Central Nervous System (CNS). These elements are produced through activation of Toll-Like Receptors (TLRs) by exogenous and endogenous ligands thereby increasing expression of cytokines and co-stimulatory molecules through the activation of TLRs 2, 3, 4, and 9 as reported in murine studies.It has been demonstrated that IL-1beta intracellular signaling and cascade is able to alter the neuronal excitability without cell loss. The activation of the IL-1beta/ IL 1beta R axis is strictly linked to the secretion of the intracellular protein MyD88, which interacts with other cell surface receptors, such as TLR4 during pathogenic recognition. Furthermore, TLR-signaling pathways are able to recognize molecules released from damaged tissues, such as damage-associated molecular patterns/proteins (DAMPs). Among these molecules, High-mobility group box-1 (HMGB1) is a component of chromatin that is passively released from necrotic cells and actively released by cells that are subject to profound stress. Moreover, recent studies have described models of epilepsy induced by the administration of bicuculline and kainic acid that highlight the nature of HMGB1 TLR4 interactions, their intracellular signaling pathway as well as their role in ictiogenesis and epileptic recurrence.The aim of our review is to focus on different branches of innate immunity and their role in epilepsy, emphasizing the role of immune related molecules in epileptogenesis and highlighting the research implications for novel therapeutic strategies. PMID- 26260964 TI - Effects of metal salt addition on odor and process stability during the anaerobic digestion of municipal waste sludge. AB - Anaerobic digestion (AD) is an effective way to recover energy and nutrients from organic waste; however, several issues including the solubilization of bound nutrients and the production of corrosive, highly odorous and toxic volatile sulfur compounds (VSCs) in AD biogas can limit its wider adoption. This study explored the effects of adding two different doses of ferric chloride, aluminum sulfate and magnesium hydroxide directly to the feed of complete mix semi continuously fed mesophilic ADs on eight of the most odorous VSCs in AD biogas at three different organic loading rates (OLR). Ferric chloride was shown to be extremely effective in reducing VSCs by up to 87%, aluminum sulfate had the opposite effect and increased VSC levels by up to 920%, while magnesium hydroxide was not shown to have any significant impact. Ferric chloride, aluminum sulfate and magnesium hydroxide were effective in reducing the concentration of orthophosphate in AD effluent although both levels of alum addition caused digester failure at elevated OLRs. Extensive foaming was observed within the magnesium hydroxide dosed digesters, particularly at higher doses and high OLRs. Certain metal salt additions may be a valuable tool in overcoming barriers to AD and to meet regulatory targets. PMID- 26260965 TI - Source segregation of food waste in office areas: Factors affecting waste generation rates and quality. AB - Existing legislation mandates that the amount of waste being recycled should be increased. Among others, in its Resource Strategy Plan, the Danish Government decided that at least 60% of food waste generated by the service sector, including in office areas, should be source-sorted and collected separately by 2018. To assess the achievability of these targets, source-sorted food waste and residual waste from office areas was collected and weighed on a daily basis during 133 working days. Waste composition analyses were conducted every week to investigate the efficiency of the source-sorting campaign and the purity of the source-sorted food waste. The moisture content of source-sorted food waste and residual waste fractions, and potential methane production from source-sorted food waste, was also investigated. Food waste generation equated to 23 +/- 5 kg/employee/year, of which 20 +/- 5 kg/employee/year was source-sorted, with a considerably high purity of 99%. Residual waste amounted to 10 +/- 5 kg/employee/year and consisted mainly of paper (29 +/- 13%), plastic (23 +/- 9%) and missorted food waste (24 +/- 16%). The moisture content of source-sorted food waste was significantly higher (8%) than missorted food waste, and the methane potential of source-sorted food waste was 463 +/- 42 mL CH4/g VS. These results show that food waste in office areas offers promising potential for relatively easily collectable and pure source-sorted food waste, suggesting that recycling targets for food waste could be achieved with reasonable logistical ease in office areas. PMID- 26260966 TI - Corrigendum to Van de Waal et al. 2014: stoichiometric regulation of phytoplankton toxins. PMID- 26260967 TI - This meta-analysis does not reflect current practice and overestimates SAEs. PMID- 26260968 TI - [Reply to: BCG vaccination recommendation in children with latent tuberculosis infection]. PMID- 26260969 TI - Polymorphisms affecting vitamin D-binding protein modify the relationship between serum vitamin D (25[OH]D3) and food allergy. AB - BACKGROUND: There is evolving evidence that vitamin D insufficiency may contribute to food allergy, but findings vary between populations. Lower vitamin D-binding protein (DBP) levels increase the biological availability of serum vitamin D. Genetic polymorphisms explain almost 80% of the variation in binding protein levels. OBJECTIVE: We sought to investigate whether polymorphisms that lower the DBP could compensate for adverse effects of low serum vitamin D on food allergy risk. METHODS: From a population-based cohort study (n = 5276) we investigated the association between serum 25-hydroxyvitamin D3 (25[OH]D3) levels and food allergy at age 1 year (338 challenge-proven food-allergic and 269 control participants) and age 2 years (55 participants with persistent and 50 participants with resolved food allergy). 25(OH)D3 levels were measured using liquid chromatography-tandem mass spectrometry and adjusted for season of blood draw. Analyses were stratified by genotype at rs7041 as a proxy marker of DBP levels (low, the GT/TT genotype; high, the GG genotype). RESULTS: Low serum 25(OH)D3 level (<=50 nM/L) at age 1 years was associated with food allergy, particularly among infants with the GG genotype (odds ratio [OR], 6.0; 95% CI, 0.9-38.9) but not in those with GT/TT genotypes (OR, 0.7; 95% CI, 0.2-2.0; P interaction = .014). Maternal antenatal vitamin D supplementation was associated with less food allergy, particularly in infants with the GT/TT genotype (OR, 0.10; 95% CI, 0.03-0.41). Persistent vitamin D insufficiency increased the likelihood of persistent food allergy (OR, 12.6; 95% CI, 1.5-106.6), particularly in those with the GG genotype. CONCLUSIONS: Polymorphisms associated with lower DBP level attenuated the association between low serum 25(OH)D3 level and food allergy, consistent with greater vitamin D bioavailability in those with a lower DBP level. This increases the biological plausibility of a role for vitamin D in the development of food allergy. PMID- 26260970 TI - Widespread somatic L1 retrotransposition occurs early during gastrointestinal cancer evolution. AB - Somatic L1 retrotransposition events have been shown to occur in epithelial cancers. Here, we attempted to determine how early somatic L1 insertions occurred during the development of gastrointestinal (GI) cancers. Using L1-targeted resequencing (L1-seq), we studied different stages of four colorectal cancers arising from colonic polyps, seven pancreatic carcinomas, as well as seven gastric cancers. Surprisingly, we found somatic L1 insertions not only in all cancer types and metastases but also in colonic adenomas, well-known cancer precursors. Some insertions were also present in low quantities in normal GI tissues, occasionally caught in the act of being clonally fixed in the adjacent tumors. Insertions in adenomas and cancers numbered in the hundreds, and many were present in multiple tumor sections, implying clonal distribution. Our results demonstrate that extensive somatic insertional mutagenesis occurs very early during the development of GI tumors, probably before dysplastic growth. PMID- 26260971 TI - Extensive de novo mutation rate variation between individuals and across the genome of Chlamydomonas reinhardtii. AB - Describing the process of spontaneous mutation is fundamental for understanding the genetic basis of disease, the threat posed by declining population size in conservation biology, and much of evolutionary biology. Directly studying spontaneous mutation has been difficult, however, because new mutations are rare. Mutation accumulation (MA) experiments overcome this by allowing mutations to build up over many generations in the near absence of natural selection. Here, we sequenced the genomes of 85 MA lines derived from six genetically diverse strains of the green alga Chlamydomonas reinhardtii. We identified 6843 new mutations, more than any other study of spontaneous mutation. We observed sevenfold variation in the mutation rate among strains and that mutator genotypes arose, increasing the mutation rate approximately eightfold in some replicates. We also found evidence for fine-scale heterogeneity in the mutation rate, with certain sequence motifs mutating at much higher rates, and clusters of multiple mutations occurring at closely linked sites. There was little evidence, however, for mutation rate heterogeneity between chromosomes or over large genomic regions of 200 kbp. We generated a predictive model of the mutability of sites based on their genomic properties, including local GC content, gene expression level, and local sequence context. Our model accurately predicted the average mutation rate and natural levels of genetic diversity of sites across the genome. Notably, trinucleotides vary 17-fold in rate between the most and least mutable sites. Our results uncover a rich heterogeneity in the process of spontaneous mutation both among individuals and across the genome. PMID- 26260972 TI - Genetic and environmental control of host-gut microbiota interactions. AB - Genetics provides a potentially powerful approach to dissect host-gut microbiota interactions. Toward this end, we profiled gut microbiota using 16s rRNA gene sequencing in a panel of 110 diverse inbred strains of mice. This panel has previously been studied for a wide range of metabolic traits and can be used for high-resolution association mapping. Using a SNP-based approach with a linear mixed model, we estimated the heritability of microbiota composition. We conclude that, in a controlled environment, the genetic background accounts for a substantial fraction of abundance of most common microbiota. The mice were previously studied for response to a high-fat, high-sucrose diet, and we hypothesized that the dietary response was determined in part by gut microbiota composition. We tested this using a cross-fostering strategy in which a strain showing a modest response, SWR, was seeded with microbiota from a strain showing a strong response, A*B19. Consistent with a role of microbiota in dietary response, the cross-fostered SWR pups exhibited a significantly increased response in weight gain. To examine specific microbiota contributing to the response, we identified various genera whose abundance correlated with dietary response. Among these, we chose Akkermansia muciniphila, a common anaerobe previously associated with metabolic effects. When administered to strain A*B19 by gavage, the dietary response was significantly blunted for obesity, plasma lipids, and insulin resistance. In an effort to further understand host microbiota interactions, we mapped loci controlling microbiota composition and prioritized candidate genes. Our publicly available data provide a resource for future studies. PMID- 26260973 TI - Validation of the VEINES-QOL quality of life instrument in venous leg ulcers: repeatability and validity study embedded in a randomised clinical trial. AB - BACKGROUND: VEINES-QOL/Sym is a disease-specific quality of life instrument for use in venous diseases of the leg. Its relative scoring system precludes comparisons between studies. There were very few venous leg ulcer patients in the validation samples. We report a validation study for venous leg ulcers and develop a scoring system which enables comparison between studies. METHODS: Four hundred fifty-one participants in the VenUS IV trial of the management of venous leg ulcers were asked to complete a VEINES-QOL questionnaire at recruitment, along with SF-12, pain, and other aspects of quality of life. VEINES-QOL was repeated after two weeks and after 4 months. Healing of ulcers was confirmed by blind assessment of digital photographs. Three scoring systems for VEINES-QOL were compared. RESULTS: No floor or ceiling effects were observed for VEINES-QOL items, item-item correlations were weak to moderate, item-score correlations were moderate. Internal reliability was good. The VEINES-Sym subscale was confirmed by factor analysis. Test-retest reliability was satisfactory for the scale scores; individual items showed moderate to good agreement. Relationships with SF-12, pain, and the quality items confirmed construct validity. Participants whose ulcers had healed showed greater mean increase in scores than did those yet to heal, though they continued to report leg problems. An intrinsic scoring method appeared superior to the original relative method. CONCLUSIONS: VEINES-QOL was suitable for use in the study of venous leg ulcers. The intrinsic scoring method should be adopted, to facilitate comparisons between studies. TRIAL REGISTRATION: VenUS IV is registered with the ISRCTN register, number ISRCTN49373072 . PMID- 26260974 TI - [Hypoglossofacial anastomosis for facial palsy treatment: Indications and results]. AB - Hypoglossofacial anastomosis is a classical surgical procedure for the treatment of facial paralysis when the trunk of the facial nerve cannot be repaired and its peripheral branches are normal. PATIENTS AND METHODS: Between 2004 and 2015, 77 patients were able to benefit from an hypoglossofacial anastomosis. The etiology of the paralysis was mainly the surgery of vestibular schwannoma, tumors of the facial nerve and diseases of the brainstem. A specific and premature speech therapy remediation was realized for all patients in order to preserve the tongue function and to upgrade the facial motricity. RESULTS: Sixty-nine patients could be studied. The House Brackmann grading scale was used to appreciate the result. Thirty-one patients are grade III, 34 grade IV and in only one case the result is a grade V despite the anastomosis works. The main predictive factor for a good result is a small delay between the onset of the paralysis and the surgery for the rehabilitation. The specific physiotherapy upgrades the result with less side effects of the anastomosis. CONCLUSION: Hypoglossofacial anastomosis is a simple and reliable surgical procedure for rehabilitation of paralysed face. The quality of the result is linked with an early surgery and a specific physiotherapy. PMID- 26260975 TI - The deposition and imaging of silica sub-micron particles in dentine. AB - OBJECTIVES: Sub-micron particles may assist in the delivery of compounds into dentine tubules. The surface interactions of the particles with dentine may prevent them from entering the tubules. The aim of this study is to investigate whether silica particles, treated with surfactants improves dentine tubules occlusion using both artificial and human tooth models METHODS: Spherical silica particles (size 130-810nm) bearing an encapsulated ruthenium luminescent complex were coated with the following surfactants: Zonyl((r)) FSA, Triton((r)) X-100 and Tween20((r)). The particles were prepared as 0.004% w/v and 0.04% w/v solutions with deionized water and were applied to the surface of; (1) in vitro model of PET ThinCertTM cell culture inserts; (2) 0.1mm thick sections of human molar teeth. RESULTS: Scanning electron and confocal fluorescence microscopy images show that particles without any coating and with TritonX-100 coating had the highest aggregation. Particles with Tween-20 are less aggregated on the surface and show inclusion in the tubules. Particles coated with fluorosurfactant Zonyl show a preference for aggregation at the tubule. With the ThinCertTM membranes high aggregation within the artificial tubules was increased by particle concentration. CONCLUSIONS: The use of silica sub-micron particles on hard dental tissues is dependent on the modification of the surface chemistry of both the particle and the dentine and the employment of the fluoromicronsurfactant may improve tubule occlusion. The use of ThinCertsTM membrane is useful in vitro model to mimic dentinal tubules and observe the ability of particles to occlude small channels. CLINICAL SIGNIFICANCE: The use of silica sub-micron particles on hard dentine tissues is dependent on the modification of the surface coating of the particles. This may influence how particles are incorporated in potential delivery vehicles applied to the dentine surface with the employment of a fluorosurfactant showing promise. PMID- 26260976 TI - Synergy of brushing mode and antibacterial use on in vivo biofilm formation. AB - OBJECTIVES: Orthodontic, multi-strand retention-wires are used as a generalized model for oral retention sites to investigate whether biofilm left-behind after powered toothbrushing in-vivo enabled better penetration of antibacterials as compared with manual brushing. METHODS: 2-cm multi-strand, stainless-steel retention-wires were placed in brackets bonded bilaterally in the upper arches of 10-volunteers. Volunteers used NaF-sodium-lauryl-sulphate-containing toothpaste and antibacterial, triclosan-containing toothpaste supplemented or not with an essential-oils containing mouthrinse. Opposite sides of the dentition including the retention-wires, were brushed manually or with a powered toothbrush. Health care-regimens were maintained for 1-week, after which wires were removed and oral biofilm was collected. RESULTS: When powered toothbrushing was applied, slightly less bacteria were collected than after manual brushing, regardless whether an antibacterial-regimen was used or not. Powered-toothbrushing combined with antibacterial-regimens yielded lower biofilm viability than manual brushing, indicating better antibacterial penetration into biofilm left-behind after powered brushing. Major shifts in biofilm composition, with a decrease in prevalence of both cariogenic species and periodontopathogens, were induced after powered brushing using an antibacterial-regimen. CONCLUSION: Oral biofilm left behind after powered brushing in-vivo enabled better penetration of antibacterials than after manual brushing. CLINICAL SIGNIFICANCE: Mechanical removal of oral biofilm is important for prevention of dental pathologies, but biofilm is always left-behind, such as in fissures, buccal pits, interproximal areas and gingival margins and around orthodontic appliances. Use of antibacterial toothpastes or mouthrinses can contribute to removal or killing of biofilm bacteria, but biofilm structure hampers antibacterial penetration. A synergy between brushing mode and antibacterial-regimen applied exists with clinically demonstrable effects. PMID- 26260977 TI - Protection of farmed camels (Camelus Dromedarius): Welfare problems and legislative perspective. AB - In the last years animal welfare has assumed an increasing interest in our society, influencing legislation to enact many provisions aimed at the protection of animals. Along with increased consumer awareness of the need to maintain ethically acceptable conditions of raised animals, scientists too have begun to investigate the conditions of animal welfare, the tools for its evaluation and for its improvement. Although there are many advances in knowledge, much remains to be investigated concerning many species considered "minor", that is, camels and dromedaries. Dromedaries, recently, have attracted the interest of some breeders following the results of studies concerning the nutritional and therapeutic properties of their products - milk in particular - that make them ideal for some particular categories of consumers, such as diabetics, obesity sufferers, lactose-intolerant subjects, menopausal women and so on. Considering their use in dairy husbandry, dromedaries are reared under intensive and/or semi intensive systems with the resulting emergence of specific needs, which should be fulfilled in order to have appropriate welfare. This paper's purpose is to give practical elements in order to find out dromedary welfare standards, promoting a comprehensive set of regulations on welfare, care and protection of this animal. PMID- 26260978 TI - Consistent quality control in ECG compression by means of direct metrics. AB - The aim of electrocardiogram (ECG) compression is to reduce the amount of data as much as possible while preserving the significant information for diagnosis. Objective metrics that are derived directly from the signal are suitable for controlling the quality of the compressed ECGs in practical applications. Many approaches have employed figures of merit based on the percentage root mean square difference (PRD) for this purpose. The benefits and drawbacks of the PRD measures, along with other metrics for quality assessment in ECG compression, are analysed in this work. We propose the use of the root mean square error (RMSE) for quality control because it provides a clearer and more stable idea about how much the retrieved ECG waveform, which is the reference signal for establishing diagnosis, separates from the original. For this reason, the RMSE is applied here as the target metric in a thresholding algorithm that relies on the retained energy. A state of the art compressor based on this approach, and its PRD-based counterpart, are implemented to test the actual capabilities of the proposed technique. Both compression schemes are employed in several experiments with the whole MIT-BIH Arrhythmia Database to assess both global and local signal distortion. The results show that, using the RMSE for quality control, the distortion of the reconstructed signal is better controlled without reducing the compression ratio. PMID- 26260979 TI - Exhaled Breath Condensate pH in Lung Cancer, the Impact of Clinical Factors. AB - PURPOSE: Lung cancer may be associated with airway acidification due to enhanced airway inflammation and oxidative stress. Exhaled breath condensate (EBC) pH is a non-invasive indicator of airway acidity; however, it is still unclear how EBC pH changes in lung cancer. The aim of the study was to investigate EBC pH in lung cancer together with clinical variables. METHODS: Thirty-five patients with lung cancer and 37 control subjects (21 patients with stable COPD and 16 non-COPD smokers) were enrolled. EBC was collected for pH, which was determined with the argon-purging method, compared among the groups and correlated with clinical variables of patients with lung cancer. RESULTS: No difference was found in EBC pH between patients with lung cancer and control subjects. However, endobronchial tumour localisation, squamous-cell carcinoma subtype and gastro-oesophageal reflux were associated with low EBC pH values. No relationship was observed between EBC pH and the presence of COPD, lung function variables or smoking history. CONCLUSIONS: Although, EBC pH is unchanged in lung cancer, lower EBC pH values are associated with distinct phenotypes. Our findings could facilitate further research on airway acidity in lung cancer. PMID- 26260980 TI - Structural Basis of Substrate Recognition by Aldehyde Dehydrogenase 7A1. AB - Aldehyde dehydrogenase 7A1 (ALDH7A1) is part of lysine catabolism and catalyzes the NAD(+)-dependent oxidation of alpha-aminoadipate semialdehyde to alpha aminoadipate. Herein, we describe a structural study of human ALDH7A1 focused on substrate recognition. Five crystal structures and small-angle X-ray scattering data are reported, including the first crystal structure of any ALDH7 family member complexed with alpha-aminoadipate. The product binds with the epsilon carboxylate in the oxyanion hole, the aliphatic chain packed into an aromatic box, and the distal end of the product anchored by electrostatic interactions with five conserved residues. This binding mode resembles that of glutamate bound to the proline catabolic enzyme ALDH4A1. Analysis of ALDH7A1 and ALDH4A1 structures suggests key interactions that underlie substrate discrimination. Structures of apo ALDH7A1 reveal dramatic conformational differences from the product complex. Product binding is associated with a 16 A movement of the C terminus into the active site, which stabilizes the active conformation of the aldehyde substrate anchor loop. The fact that the C-terminus is part of the active site was hitherto unknown. Interestingly, the C-terminus and aldehyde anchor loop are disordered in a new tetragonal crystal form of the apoenzyme, implying that these parts of the enzyme are highly flexible. Our results suggest that the active site of ALDH7A1 is disassembled when the aldehyde site is vacant, and the C-terminus is a mobile element that forms quaternary structural interactions that aid aldehyde binding. These results are relevant to the c.1512delG genetic deletion associated with pyridoxine-dependent epilepsy, which alters the C-terminus of ALDH7A1. PMID- 26260981 TI - Purifying Cytokinetic Cells from an Asynchronous Population. AB - Cytokinesis is an intensively studied process by which the cell cytoplasm divides to produce two daughter cells. Like any other aspect of cell cycle research, the study of cytokinesis relies heavily on cell synchronization. However, the synchronization of cells during cytokinesis is challenging due to the rapid nature of this process and the shortage of cell cycle blocking agents specifically targeting this phase. Here, we demonstrate the use of standard flow cytometry for directly isolating cytokinetic cells from an asynchronous population of normally proliferating cells. This approach is based on a cell cycle marker whose temporal proteolysis, in combination with DNA quantification or cell size approximation, distinguishes cells undergoing cytokinesis. Furthermore, by avoiding doublet discrimination, typically used in flow cytometry analyses, we were able to further increase selectivity, specifically purifying cells at late cytokinesis. Our method circumvents checkpoint activation, cell cycle arrest, and any other means of pre-synchronization. These qualities, as demonstrated for both unattached and adherent cells, enable high selectivity for cytokinetic cells despite their overall low abundance in an asynchronous population. The sorted cells can then be readily used for cell biological, biochemical, and genomic applications to facilitate cytokinesis and cell cycle research. PMID- 26260982 TI - "It puts a human face on the researched"--A qualitative evaluation of an Indigenous health research governance model. AB - OBJECTIVE: To describe the Inala Aboriginal and Torres Strait Islander Community Jury for Health Research, and evaluate its usefulness as a model of Indigenous research governance within an urban Indigenous primary health care service from the perspectives of jury members and researchers. METHODS: Informed by a phenomenological approach and using narrative inquiry, a focus group was conducted with jury members and key informant interviews were undertaken with researchers who had presented to the Community Jury in its first year of operation. RESULTS: The jury was a site of identity work for researchers and jury members, providing an opportunity to observe and affirm community cultural protocols. Although researchers and jury members had differing levels of research literacy, the jury processes enabled respectful communication and relationships to form, which positively influenced research practice, community aspirations and clinical care. DISCUSSION: The jury processes facilitated transformative research practice among researchers and resulted in transference of power from researchers to the jury members, to the mutual benefit of both. CONCLUSION: Ethical Indigenous health research practice requires an engagement with Indigenous peoples and knowledge at the research governance level, not simply as subjects or objects of research. PMID- 26260983 TI - Pediatric tuberculous meningitis: Model-based approach to determining optimal doses of the anti-tuberculosis drugs rifampin and levofloxacin for children. AB - Pediatric tuberculous meningitis (TBM) is a highly morbid, often fatal disease. Standard treatment includes isoniazid, rifampin, pyrazinamide, and ethambutol. Current rifampin dosing achieves low cerebrospinal fluid (CSF) concentrations, and CSF penetration of ethambutol is poor. In adult trials, higher-dose rifampin and/or a fluoroquinolone reduced mortality and disability. To estimate optimal dosing of rifampin and levofloxacin for children, we compiled plasma and CSF pharmacokinetic (PK) and outcomes data from adult TBM trials plus plasma PK data from children. A population PK/pharmacodynamic (PD) model using adult data defined rifampin target exposures (plasma area under the curve (AUC)0-24 = 92 mg*h/L). Levofloxacin targets and rifampin pediatric drug disposition information were literature-derived. To attain target rifampin exposures, children require daily doses of at least 30 mg/kg orally or 15 mg/kg intravenously (i.v.). From our pediatric population PK model, oral levofloxacin doses needed to attain exposure targets were 19-33 mg/kg. Our results provide data-driven guidance to maximize pediatric TBM treatment while we await definitive trial results. PMID- 26260984 TI - Sex-Specific Association between Longitudinal Changes in Adiposity, FTO rs9939609 Polymorphism, and Leukocyte Telomere Length. AB - OBJECTIVE: A longitudinal study was conducted to examine sex-specific associations between changes in adiposity over a 10-year period, the FTO rs9939609 polymorphism, and leukocyte telomere length (LTL). METHODS: A population-based cohort including 2128 middle-aged and older Korean men (n = 1087) and women (n = 1041) participated in a prospective study. Anthropometric measurements of weight, height, and waist and hip circumference were taken at baseline (from 2001 to 2003) and at the 10-year follow-up period (from 2011 to 2012). The FTO rs9939609 polymorphism was genotyped using DNA samples collected at baseline and LTL was assessed at the 10-year follow-up period. Multiple linear regression analysis was used with adjustments for age, baseline body mass index, and other potential confounders. RESULTS: Presence of the FTO rs9939609 polymorphism risk allele was inversely associated with LTL (p < 0.01) in all participants, with a significant association seen only in women when the genders were modeled separately. Conversely, a significant inverse association between changes in waist circumference and LTL was found in men (p < 0.001) but not in women. No significant interaction between adiposity measures and the FTO polymorphism in association with LTL was identified for either sex. CONCLUSIONS: These data suggest that biological aging in men may be accelerated by increasing waist circumference, whereas in women, aging may be affected by genetic variations in FTO regardless of adiposity changes over time. PMID- 26260985 TI - The Changing Role of ENGOs in Water Governance: Institutional Entrepreneurs? AB - The changing role of the state in the last quarter century has been an important contemporary concern for policy makers, scholars, and the public. Equally, there is increasing recognition among governance scholars that nongovernment actors are exerting new kinds of influence over governance systems and contributing in novel ways to governance processes. The role of environmental nongovernmental organizations (ENGOs) is particularly pertinent given the continued involvement of ENGOs within collaborative, adaptive, and co-management governance, across several contexts and regions. This paper uses an analytical framework derived from recent studies on institutional entrepreneurs, to examine the skills ENGOs are applying in order to orchestrate change. An empirical case of governance for water in Canada's Lake Simcoe region provides the foundation for the research. Drawing on a mixed methods approach, the research finds that ENGOs in Lake Simcoe have taken on a role as an institutional entrepreneur, and thereby have altered the relationship between governance actors in this setting. A key outcome of their actions is a more dominant, engaged, and influential role for ENGOs in a critical, regional governance system. PMID- 26260987 TI - A recent epidemiological cluster of acute hepatitis B genotype F1b infection in a restricted geographical area of Italy. AB - In this study, by phylogenetic analysis, we identified an epidemiological cluster involving eight individuals diagnosed with acute hepatitis B virus (HBV) infection related to unprotected sexual intercourse in a restricted area of central Italy (time period: 2011-2014). Notably, these patients (six of eight Italians) were infected by subgenotype F1b, which is not commonly found in western countries. Ultra-deep pyrosequencing confirmed a superimposable composition of HBV quasi-species in these patients. Despite the availability of effective vaccination, this study highlights the importance of not underestimating the risk of HBV infection, of continuing to set up surveillance programmes for HBV infection, and of investigating the pathogenetic potential of these atypical genotypes. PMID- 26260986 TI - Differential Gene Expression in Liver, Gill, and Olfactory Rosettes of Coho Salmon (Oncorhynchus kisutch) After Acclimation to Salinity. AB - Most Pacific salmonids undergo smoltification and transition from freshwater to saltwater, making various adjustments in metabolism, catabolism, osmotic, and ion regulation. The molecular mechanisms underlying this transition are largely unknown. In the present study, we acclimated coho salmon (Oncorhynchus kisutch) to four different salinities and assessed gene expression through microarray analysis of gills, liver, and olfactory rosettes. Gills are involved in osmotic regulation, liver plays a role in energetics, and olfactory rosettes are involved in behavior. Between all salinity treatments, liver had the highest number of differentially expressed genes at 1616, gills had 1074, and olfactory rosettes had 924, using a 1.5-fold cutoff and a false discovery rate of 0.5. Higher responsiveness of liver to metabolic changes after salinity acclimation to provide energy for other osmoregulatory tissues such as the gills may explain the differences in number of differentially expressed genes. Differentially expressed genes were tissue- and salinity-dependent. There were no known genes differentially expressed that were common to all salinity treatments and all tissues. Gene ontology term analysis revealed biological processes, molecular functions, and cellular components that were significantly affected by salinity, a majority of which were tissue-dependent. For liver, oxygen binding and transport terms were highlighted. For gills, muscle, and cytoskeleton-related terms predominated and for olfactory rosettes, immune response-related genes were accentuated. Interaction networks were examined in combination with GO terms and determined similarities between tissues for potential osmosensors, signal transduction cascades, and transcription factors. PMID- 26260988 TI - Antigen-Induced Activation of Antibody Measured by Fluorescence Enhancement of FITC Label at Fc. AB - Three anti-carbohydrate antibodies of defined specificity isolated from plasma were used to demonstrate that macromolecular antigen binding caused considerable enhancement of fluorescence of FITC-labeled antibody. Mono and disaccharide antigens which could compete with the large antigens in antibody binding could not however produce any increase in fluorescence. Fluorescence enhancement in a given antibody sample increased with the size of the occupying macromolecular antigen. Conversely in antibody samples of same ligand specificity isolated from plasma of different individuals, fluorescence enhancement produced by the same antigen correlated with specific activity of the antibody sample. Removal of Fc part of antibody, confirmed by electrophoresis and Fc-specific antibody binding, caused abolition of most of the antigen-driven fluorescence increase. Since antigen binding sites of antibodies were protected during FITC labeling, the above results suggest that conformational shift in Fc produced by occupation of binding sites by large antigens resulted in the enhancement of fluorescence of FITC tags on Fc. Data provides a tool for detection and measurement of specific ligands using fluorolabeled whole antibodies. PMID- 26260989 TI - White Light Emission Through Downconversion of Terbium and Europium Doped CeF3 Nanophosphors. AB - CeF3 nanophosphors have been extensively investigated in recent years for lighting and numerous bio-applications. Downconversion emissions in CeF3:Eu(3+)/Tb(3+) phosphors were studied with the objective of attaining a white light emitting composition, by means of a simple co-precipitation method. The material was characterized by X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM), Fourier Transform Infrared Spectroscopy (FT-IR) and Photoluminescence (PL). Uniformly distributed nanoparticles were obtained with an average particle size range of 8-10 nm. Various studies were undertook utilizing different doping concentrations and respective fluorescence studies were carried out to optimize dopant concentrations while achieving maximum luminescence intensity. From PL results, it was observed that the efficient energy transfers from the donor to the acceptor ions. Different concentrations of Tb(3+), Eu(3+) were doped in order to achieve a white light emitting phosphor for UV-based Light Emitting Diodes (LEDs). The nanoparticles showed characteristic emission of respective dopants (Eu(3+), Tb(3+)) when excited at the 4f -> 5d transition of Ce(3+). The chromaticity coordinates for CeF3 doped with Eu(3+) and Tb(3+) were calculated and an emission very close to white light was observed. PMID- 26260990 TI - The chloride-bicarbonate exchanger pendrin is increased in the kidney of the pregnant rat. AB - NEW FINDINGS: What is the central question of this study? Pregnancy requires a robust plasma volume expansion driven by renal sodium retention. In the late pregnant kidney, the aldosterone-responsive epithelial Na(+) channel is increased, whereas the sodium-chloride cotransporter is decreased. Pendrin has been shown to support sodium reabsorption in the distal nephron and compensate for loss of the sodium-chloride cotransporter. We investigated the expression and abundance of pendrin in the pregnant kidney. What is the main finding and its importance? Pendrin protein, apical localization and thiazide sensitivity are increased in pregnancy. This implicates a possible role for pendrin in supporting the renal sodium chloride reabsorption and plasma volume expansion of pregnancy. Pregnancy is characterized by cumulative plasma volume expansion as a result of renal sodium retention, driven by activation of aldosterone. We previously reported that the abundance and activity of the aldosterone-responsive epithelial Na(+) channel is increased, whereas the sodium-chloride cotransporter (NCC) is decreased in the kidney of the late-pregnant rat. The chloride-bicarbonate exchanger pendrin is also aldosterone responsive and has been shown to support activity of the aldosterone-responsive epithelial Na(+) channel and compensate for the loss of NCC. Additionally, pendrin coupled to the sodium-dependent chloride-bicarbonate exchanger (NDCBE) mediates thiazide-sensitive sodium reabsorption in the cortical collecting duct. In this study, we investigated pendrin and NDCBE transcript expression, pendrin protein abundance, pendrin cellular localization and thiazide sensitivity in virgin, mid-pregnant and late pregnant rats to test the hypothesis that increased pendrin activity might occur in pregnancy. By RT-PCR, NDCBE and pendrin mRNA expression was unchanged from virgins, whereas pendrin protein abundance determined by Western blotting was increased in both mid- and late-pregnant rats. The apical localization of pendrin was also increased in late-pregnant rats compared with virgins by immunohistochemistry. Pregnant rats displayed an increased natriuretic response to hydrochlorothiazide compared with virgins. Given that NCC expression is decreased in late pregnancy, an increased thiazide sensitivity may be due to inhibition of upregulated pendrin-NDCBE-coupled sodium reabsorption. Thus, increased pendrin in pregnant rats may compensate for the decreased NCC and aid in the renal sodium chloride reabsorption of pregnancy. PMID- 26260991 TI - Social and Structural Factors Shaping High Rates of Incarceration among Sex Workers in a Canadian Setting. AB - In light of the emphasis on enforcement-based approaches towards sex work, and the well-known negative impacts of these approaches on women's health, safety and well-being, we conducted a study to investigate the prevalence and correlates of recent incarceration among a cohort of women sex workers in Vancouver, Canada. Data were obtained from an open prospective community cohort of female and transgender women sex workers, known as An Evaluation of Sex Workers' Health Access (AESHA). Bivariate and multivariable logistic regression analyses, using generalized estimating equations (GEE), were used to model the effect of social and structural factors on the likelihood of incarceration over the 44-month follow-up period (January 2010-August 2013). Among 720 sex workers, 62.5 % (n = 450) reported being incarcerated in their lifetime and 23.9 % (n = 172) being incarcerated at least once during the study period. Of the 172 participants, about one third (36.6 %) reported multiple episodes of incarceration. In multivariable GEE analyses, younger age (adjusted odds ratio [AOR] = 1.04 per year younger, 95 % confidence interval [CI] 1.02-1.06), being of a sexual/gender minority (AOR = 1.62, 95 % CI 1.13-2.34), heavy drinking (AOR = 1.99, 95 % CI 1.20-3.29), being born in Canada (AOR = 3.28, 95 % CI 1.26-8.53), living in unstable housing conditions (AOR = 4.32, 95 % CI 2.17-8.62), servicing clients in public spaces (versus formal sex work establishments) (AOR = 2.33, 95 % CI 1.05 5.17) and experiencing police harassment without arrest (AOR = 1.82, 95 % CI 1.35 2.45) remain independently correlated with incarceration. This prospective study found a very high prevalence and frequency of incarceration among women sex workers in Vancouver, Canada, with the most vulnerable and marginalized women at increased risk of incarceration. Given the well-known social and health harms associated with incarceration, and associations between police harassment and incarceration in this study, our findings further add to growing calls to move away from criminalized and enforcement-based approaches to sex work in Canada and globally. PMID- 26260992 TI - Differential crosstalk between the AMPK and PI3K/Akt pathways in breast cancer cells of differing genotypes: Leptin inhibits the effectiveness of AMPK activation. AB - AMP-activated protein kinase (AMPK), a sensor of cellular energy, is widely reported as a potential therapeutic target in treatment of breast and other cancers. The activated enzyme has been shown to be a promising anti-proliferative agent in breast cancer cell lines. However, little data exist on crosstalk between AMPK and the cellular survival axis of PI3K/Akt/mTOR pathway and the impact of microenvironment on cellular responses to AMPK activation. We present results which show differential crosstalk between AMPK and Akt, dependent on the cellular genetics of each breast cancer cell type. We also show that leptin blocks activation of AMPK and partially or completely attenuates the anti proliferative effect of AMPK activation depending on the cell type. This suggests that leptin within the local environment might impose limitations on therapeutic usage of AMPK activators in cancer, thereby attenuating their effective use in many obese subjects. PMID- 26260993 TI - Delay in Diagnosis of Spinal Muscular Atrophy: A Systematic Literature Review. AB - BACKGROUND: Spinal muscular atrophy is a rare genetic disease with devastating neurodegenerative consequences. Timing of diagnosis is crucial for spinal muscular atrophy because early diagnosis may lead to early supportive care and reduction in patient and caregiver stress. The purpose of this study was to examine the published literature for diagnostic delay in spinal muscular atrophy. METHODS: A systematic literature search was conducted in the PubMed and Web of Science databases for studies published between 2000 and 2014 that listed any type of spinal muscular atrophy and without molecular, mouse, or pathology in the keywords. Mean and/or median age of onset and diagnosis and delay in diagnosis was extracted or calculated. All estimates were weighted by the number of patients and descriptive statistics are reported. RESULTS: A total of 21 studies were included in the final analysis. The weighted mean (standard deviation) ages of onset were 2.5 (0.6), 8.3 (1.6), and 39.0 (32.6) months for spinal muscular atrophy types I, II, and III, respectively, and the weighted mean (standard deviation) ages of confirmed spinal muscular atrophy genetic diagnosis were 6.3 (2.2), 20.7 (2.6), and 50.3 (12.9) months, respectively, for types I, II, and III. For studies reporting both age of onset and diagnosis, the weighted diagnostic delay was 3.6, 14.3, and 43.6 months for types I, II, and III, respectively. CONCLUSIONS: Diagnostic delay is common in spinal muscular atrophy. The length of delay varied by severity (type) of spinal muscular atrophy. Further studies evaluating this delay and tools such as newborn screening are warranted to end the diagnostic delay in spinal muscular atrophy. PMID- 26260994 TI - Bilateral Paramedian Thalamic Syndrome After Infection. PMID- 26260995 TI - Reply to Huo et al. PMID- 26260996 TI - Paucity of PD-L1 expression in prostate cancer: innate and adaptive immune resistance. AB - BACKGROUND: Primary prostate cancers are infiltrated with programmed death-1 (PD 1) expressing CD8+ T-cells. However, in early clinical trials, men with metastatic castrate-resistant prostate cancer did not respond to PD-1 blockade as a monotherapy. One explanation for this unresponsiveness could be that prostate tumors generally do not express programmed death ligand-1 (PD-L1), the primary ligand for PD-1. However, lack of PD-L1 expression in prostate cancer would be surprising, given that phosphatase and tensin homolog (PTEN) loss is relatively common in prostate cancer and several studies have shown that PTEN loss correlates with PD-L1 upregulation--constituting a mechanism of innate immune resistance. This study tested whether prostate cancer cells were capable of expressing PD-L1, and whether the rare PD-L1 expression that occurs in human specimens correlates with PTEN loss. METHODS: Human prostate cancer cell lines were evaluated for PD-L1 expression and loss of PTEN by flow cytometry and western blotting, respectively. Immunohistochemical (IHC) staining for PTEN was correlated with PD-L1 IHC using a series of resected human prostate cancer samples. RESULTS: In vitro, many prostate cancer cell lines upregulated PD-L1 expression in response to inflammatory cytokines, consistent with adaptive immune resistance. In these cell lines, no association between PTEN loss and PD-L1 expression was apparent. In primary prostate tumors, PD-L1 expression was rare, and was not associated with PTEN loss. CONCLUSIONS: These studies show that some prostate cancer cell lines are capable of expressing PD-L1. However, in human prostate cancer, PTEN loss is not associated with PD-L1 expression, arguing against innate immune resistance as a mechanism that mitigates antitumor immune responses in this disease. PMID- 26260997 TI - Rectal swab testing before prostate biopsy: experience in a VA Medical Center urology practice. AB - BACKGROUND: Infectious complications following transrectal ultrasound prostate biopsy (TRUSBx) have been increasing. Pre-biopsy prophylaxis with fluoroquinolone (FQL) antibiotics is a recommended and accepted practice. Increasing emergence of FQL-resistant bacteria is believed to be related to the increase in infectious complications. We sought to determine the effect of targeted antibiotic prophylaxis (TAP) before TRUSBx on infectious complications in our practice. METHODS: TAP was introduced in our practice in 2012. A retrospective analysis was performed analyzing infectious complications from TRUSBx before and after TAP was introduced. Two hundred forty-four patients underwent TRUSBx with TAP directed by bacterial antibiotic sensitivity identified on rectal swab. A group of two hundred sixty-four consecutive patients who underwent TRUSBx in our practice before introduction of TAP were chosen for comparison. Infectious complications were recorded and compared between groups. Prostate volume, PSA, number of biopsy cores, finding of prostate cancer, presence of diabetes, race and age were also compared. RESULTS: The infectious complication rate after TRUSBx in the pre-TAP group was 7/264 (2.65%), the rate in the TAP group was 1/244 (0.41%), a statistically significant difference (P=<0.05). There were no differences between groups in regards to prostate volume, number of prostate biopsy cores, race and presence of diabetes. The rectal swab group was younger (65.4 +/- 6.0) than the non-swab group (67.9 +/- 6.2), had higher PSA values, and a higher chance of prostate cancer on biopsy. CONCLUSIONS: The use of TAP based on rectal swab testing significantly lowered our infectious complication rate for TRUSBx. TAP is now adopted as standard practice before TRUSBx in our center. The younger age and higher chance of prostate cancer on biopsy in the rectal swab group, we believe, is due to implementation of recent guidelines directing urologists be more selective in recommending prostate biopsy to older men. PMID- 26260998 TI - Shotgun metaproteomic profiling of biomimetic anaerobic digestion processes treating sewage sludge. AB - Two parallel anaerobic digestion lines were designed to match a "bovid-like" digestive structure. Each of the lines consisted of two continuous stirred tank reactors placed in series and separated by an acidic treatment step. The first line was inoculated with industrial inocula whereas the second was seeded with cow digestive tract contents. After 3 months of continuous sewage sludge feeding, samples were recovered for shotgun metaproteomic and DNA-based analysis. Strikingly, protein-inferred and 16S ribosomal DNA tags based taxonomic community profiles were not consistent. PCA however revealed a similar clustering pattern of the samples, suggesting that reproducible methodological and/or biological factors underlie this observation. The performances of the two digestion lines did not differ significantly and the cow-derived inocula did not establish in the reactors. A low throughput metagenomic dataset (3.4 * 10(6) reads, 1.1 Gb) was also generated for one of the samples. It allowed a substantial increase of the analysis depth (11 vs. 4% of spectral identification rate for the combined samples). Surprisingly, a high proportion of proteins from members of the "Candidatus Competibacter" group, a key microbial player usually found in activated sludge plants, was retrieved in our anaerobic digester samples. Data are available via ProteomeXchange with identifier PXD002420 (http://proteomecentral.proteomexchange.org/dataset/PXD002420). PMID- 26260999 TI - Preparation, quality control and biodistribution assessment of 153Sm-BPAMD as a novel agent for bone pain palliation therapy. AB - OBJECTIVE: Various phosphonate ligands labeled with beta(-)-emitting radionuclides have shown good efficacy for bone pain palliation. In this study, a new agent for bone pain palliation has been developed. METHODS: 153Sm-(4 {[(bis(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10 tetraazacyclododec-1-yl) acetic acid (153Sm-BPAMD) complex was prepared using BPAMD ligand and 153SmCl3. The effect of various parameters on the labeling yield of 153Sm-BPAMD including ligand concentration, pH, temperature and reaction time were studied. Radiochemical purity of the radiolabeled complex was checked by instant thin layer chromatography (ITLC). Stability studies of the complex in the final preparation and in the presence of human serum were performed up to 48 h. Partition coefficient and hydroxyapatite (HA) binding of the complex were investigated and biodistribution studies (SPECT imaging and scarification) were performed after injection of the complex to Syrian mice up to 48 h post injection. The biodistribution of the complex was compared with the biodistribution of the 153Sm cation in the same type mice. RESULTS: 153Sm-BPAMD was prepared in high radiochemical purity >98% and specific activity of 267 GBq/mmol at the optimal conditions. The complex demonstrated significant stability at room temperature and in human serum at least for 48 h. HA binding assay demonstrated that at the amount of more than 5 mg, approximately, all radiolabeled complex was bound to HA. At the pH 7.4, LogP o/w was -1.86 +/- 0.02. Both SPECT and scarification showed major accumulation of the labeled compound in the bone tissue. CONCLUSION: The results show that 153Sm-BPAMD has interesting characteristics as an agent for bone pain palliation; however, further biological studies in other mammals are still needed. PMID- 26261000 TI - Detection of local recurrence of prostate cancer after radical prostatectomy: Is there a role for early 18F-FCH PET/CT? AB - AIM: To investigate the diagnostic performance of early acquisition compared to late imaging for the detection of local recurrence of prostate cancer by means of 18F-FCH PET/CT. MATERIALS AND METHODS: 99 patients with radical prostatectomy (mean PSA 3.9 +/- 5.03) were subjected to early dynamic PET/CT acquisition of the pelvis and a whole body PET/CT in the same exam session. None of the patients examined was subjected to radiotherapy for local or distant recurrence. All the subjects were taken off hormonal therapy. RESULTS: 58 subjects did not show local recurrence in both early and late acquisition, 22 were positive in both modalities, 10 showed a positive early and a negative late acquisition while 9 showed a negative early and a positive late acquisition (Cohen's k = 0.558). When the results of imaging modalities were considered separately, sensitivity, specificity, positive predictive value and negative predictive value resulted: 78.9, 96.7, 93.8 and 88.1 % for early acquisition and 73.7, 95.1, 90.3 and 85.3 % for late acquisition, respectively. When the results of early and late acquisition were considered together, results were 97.4, 93.4, 90.2 and 98.3 %, respectively. CONCLUSIONS: The combination of early acquisition with late acquisition lead to an increase of the diagnostic accuracy of 18F-FCH PET/CT for the diagnosis of local recurrence in prostate cancer. PMID- 26261002 TI - Brief screening of patients with distressing fear of recurrence in breast cancer survivors. PMID- 26261003 TI - 3D motion reliability of occipital condylar glide testing: From concept to kinematics evidence. AB - BACKGROUND: To date, segmental data analyzing kinematics of occipital condylar testing or mobilization is lacking. OBJECTIVES: The objective of this study was to assess occipitoatlantal 3D motion components and to analyze inter- and intra rater reliability during in vitro condylar glide test. METHODS: To conduct this study, four fresh cadavers were included. Dissection was carried out to ensure technical clusters placement to skull, C1 and C2. During condylar glide test, bone motion data was computed using an optoelectronic system. The reliability of motion kinematics was assessed for three skilled practitioners performing two sessions of 3 trials on two days interval. FINDINGS: During testing, average absolute motion ROM (+/-SD) were up to 4.1 +/- 2.1 degrees , 0.7 +/- 1.3 degrees and 10.3 +/- 2.5 degrees for occipitoatlantal lateral bending, axial rotation and flexion-extension, respectively. For position variation, magnitudes were 2.3 +/- 1.8 mm, 1.1 +/- 1.3 mm and 2.6 +/- 0.8 mm for anteroposterior, cephalocaudal and mediolateral displacements. Concerning motion reliability, variation ranged from 0.6 degrees to 3.4 degrees and from 0.3 mm to 1.6 mm for angular displacement and condyle position variation, respectively. In general, good to excellent agreement was observed (ICC ranging from 0.728 to 0.978) for the same operator, while consistency was limited to lateral/side bending and lateral condyle displacement between operators, with respective ICCs of 0.800 and 0.955. CONCLUSIONS: This study shows specific motion patterns involving extension and lateral bending of the occipitoatlantal level for anterior condylar glide test. In addition, condyle position variation demonstrated coupled components in forward and heterolateral directions. However, task seems not to be side specific. In general, reliability of 3D motion components showed good intra operator agreement and limited inter-operator agreement. PMID- 26261001 TI - Mechanisms of antimicrobial resistance in Gram-negative bacilli. AB - The burden of multidrug resistance in Gram-negative bacilli (GNB) now represents a daily issue for the management of antimicrobial therapy in intensive care unit (ICU) patients. In Enterobacteriaceae, the dramatic increase in the rates of resistance to third-generation cephalosporins mainly results from the spread of plasmid-borne extended-spectrum beta-lactamase (ESBL), especially those belonging to the CTX-M family. The efficacy of beta-lactam/beta-lactamase inhibitor associations for severe infections due to ESBL-producing Enterobacteriaceae has not been adequately evaluated in critically ill patients, and carbapenems still stands as the first-line choice in this situation. However, carbapenemase producing strains have emerged worldwide over the past decade. VIM- and NDM-type metallo-beta-lactamases, OXA-48 and KPC appear as the most successful enzymes and may threaten the efficacy of carbapenems in the near future. ESBL- and carbapenemase-encoding plasmids frequently bear resistance determinants for other antimicrobial classes, including aminoglycosides (aminoglycoside-modifying enzymes or 16S rRNA methylases) and fluoroquinolones (Qnr, AAC(6')-Ib-cr or efflux pumps), a key feature that fosters the spread of multidrug resistance in Enterobacteriaceae. In non-fermenting GNB such as Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia, multidrug resistance may emerge following the sole occurrence of sequential chromosomal mutations, which may lead to the overproduction of intrinsic beta-lactamases, hyper expression of efflux pumps, target modifications and permeability alterations. P. aeruginosa and A. baumannii also have the ability to acquire mobile genetic elements encoding resistance determinants, including carbapenemases. Available options for the treatment of ICU-acquired infections due to carbapenem-resistant GNB are currently scarce, and recent reports emphasizing the spread of colistin resistance in environments with high volume of polymyxins use elicit major concern. PMID- 26261004 TI - Twelve recommendations for integrating existing systematic reviews into new reviews: EPC guidance. AB - OBJECTIVES: As time and cost constraints in the conduct of systematic reviews increase, the need to consider the use of existing systematic reviews also increases. We developed guidance on the integration of systematic reviews into new reviews. METHODS: A workgroup of methodologists from Evidence-based Practice Centers developed consensus-based recommendations. Discussions were informed by a literature scan and by interviews with organizations that conduct systematic reviews. RESULTS: Twelve recommendations were developed addressing selecting reviews, assessing risk of bias, qualitative and quantitative synthesis, and summarizing and assessing body of evidence. CONCLUSIONS: We provide preliminary guidance for an efficient and unbiased approach to integrating existing systematic reviews with primary studies in a new review. PMID- 26261005 TI - Increased Expression of DUOX2 Is an Epithelial Response to Mucosal Dysbiosis Required for Immune Homeostasis in Mouse Intestine. AB - BACKGROUND & AIMS: Dual oxidase 2 (DUOX2), a hydrogen-peroxide generator at the apical membrane of gastrointestinal epithelia, is up-regulated in patients with inflammatory bowel disease (IBD) before the onset of inflammation, but little is known about its effects. We investigated the role of DUOX2 in maintaining mucosal immune homeostasis in mice. METHODS: We analyzed the regulation of DUOX2 in intestinal tissues of germ-free vs conventional mice, mice given antibiotics or colonized with only segmented filamentous bacteria, mice associated with human microbiota, and mice with deficiencies in interleukin (IL) 23 and IL22 signaling. We performed 16S ribosomal RNA gene quantitative polymerase chain reaction of intestinal mucosa and mesenteric lymph nodes of Duoxa(-/-) mice that lack functional DUOX enzymes. Genes differentially expressed in Duoxa(-/-) mice compared with co-housed wild-type littermates were correlated with gene expression changes in early-stage IBD using gene set enrichment analysis. RESULTS: Colonization of mice with segmented filamentous bacteria up-regulated intestinal expression of DUOX2. DUOX2 regulated redox signaling within mucosa associated microbes and restricted bacterial access to lymphatic tissues of the mice, thereby reducing microbiota-induced immune responses. Induction of Duox2 transcription by microbial colonization did not require the mucosal cytokines IL17 or IL22, although IL22 increased expression of Duox2. Dysbiotic, but not healthy human microbiota, activated a DUOX2 response in recipient germ-free mice that corresponded to abnormal colonization of the mucosa with distinct populations of microbes. In Duoxa(-/-) mice, abnormalities in ileal mucosal gene expression at homeostasis recapitulated those in patients with mucosal dysbiosis. CONCLUSIONS: DUOX2 regulates interactions between the intestinal microbiota and the mucosa to maintain immune homeostasis in mice. Mucosal dysbiosis leads to increased expression of DUOX2, which might be a marker of perturbed mucosal homeostasis in patients with early-stage IBD. PMID- 26261006 TI - Identification of GLI Mutations in Patients With Hirschsprung Disease That Disrupt Enteric Nervous System Development in Mice. AB - BACKGROUND & AIMS: Hirschsprung disease is characterized by a deficit in enteric neurons, which are derived from neural crest cells (NCCs). Aberrant hedgehog signaling disrupts NCC differentiation and might cause Hirschsprung disease. We performed genetic analyses to determine whether hedgehog signaling is involved in pathogenesis. METHODS: We performed deep-target sequencing of DNA from 20 patients with Hirschsprung disease (16 men, 4 women), and 20 individuals without (controls), and searched for mutation(s) in GLI1, GLI2, GLI3, SUFU, and SOX10. Biological effects of GLI mutations were tested in luciferase reporter assays using HeLa or neuroblastoma cell lines. Development of the enteric nervous system was studied in Sufu(f/f), Gli3(Delta699), Wnt1-Cre, and Sox10(NGFP) mice using immunohistochemical and whole-mount staining procedures to quantify enteric neurons and glia and analyze axon fasciculation, respectively. NCC migration was studied using time-lapse imaging. RESULTS: We identified 3 mutations in GLI in 5 patients with Hirschsprung disease but no controls; all lead to increased transcription of SOX10 in cell lines. SUFU, GLI, and SOX10 form a regulatory loop that controls the neuronal vs glial lineages and migration of NCCs. Sufu mutants mice had high Gli activity, due to loss of Sufu, disrupting the regulatory loop and migration of enteric NCCs, leading to defective axonal fasciculation, delayed gut colonization, or intestinal hypoganglionosis. The ratio of enteric neurons to glia correlated inversely with Gli activity. CONCLUSIONS: We identified mutations that increase GLI activity in patients with Hirschsprung disease. Disruption of the SUFU-GLI-SOX10 regulatory loop disrupts migration of NCCs and development of the enteric nervous system in mice. PMID- 26261007 TI - Efficacy of ledipasvir and sofosbuvir, with or without ribavirin, for 12 weeks in patients with HCV genotype 3 or 6 infection. AB - BACKGROUND & AIMS: We performed a phase 2 clinical trial to evaluate the efficacy and safety of ledipasvir and sofosbuvir, with or without ribavirin, in patients infected with hepatitis C virus (HCV) genotype 3 or 6. METHODS: We performed an open-label study of 126 patients with HCV genotype 3 or 6 infections at 2 centers in New Zealand from April 2013 through October 2014. Subjects were assigned 1 of 4 groups that received 12 weeks of treatment. Previously untreated patients with HCV genotype 3 were randomly assigned to groups given fixed-dose combination tablet of ledipasvir and sofosbuvir (n = 25) or ledipasvir and sofosbuvir along with ribavirin (n = 26). Treatment-experienced patients with HCV genotype 3 (n = 50) received ledipasvir and sofosbuvir and ribavirin. Treatment-naive or treatment-experienced patients with HCV genotype 6 (n = 25) received ledipasvir and sofosbuvir. The primary end point was the percentage of patients with HCV RNA <=15 IU/mL 12 weeks after stopping therapy (sustained virologic response at 12 weeks [SVR12]). RESULTS: Among treatment-naive genotype 3 patients, 16 of 25 (64%) receiving ledipasvir and sofosbuvir alone achieved SVR12 compared with all 26 patients (100%) receiving ledipasvir and sofosbuvir and ribavirin. Among treatment-experienced patients with HCV genotype 3, forty-one of fifty achieved an SVR12 (82%). Among patients with HCV genotype 6, the rate of SVR12 was 96% (24 of 25 patients). The most common adverse events were headache, upper respiratory infection, and fatigue. One patient with HCV genotype 3 discontinued ledipasvir and sofosbuvir because of an adverse event (diverticular perforation), which was not considered treatment related. CONCLUSIONS: In an uncontrolled, open-label trial, high rates of SVR12 were achieved by patients with HCV genotype 3 infection who received 12 weeks of ledipasvir and sofosbuvir plus ribavirin, and by patients with HCV genotype 6 infection who received 12 weeks of sofosbuvir and ledipasvir without ribavirin. Current guidelines do not recommend the use of ledipasvir and sofosbuvir, with or without ribavirin, in patients with HCV genotype 3 infection. ClinicalTrials.gov Number: NCT01826981. PMID- 26261010 TI - Designing Photocatalysts for Hydrogen Evolution: Are Complex Preparation Strategies Necessary to Produce Active Catalysts? AB - A facile synthetic route for the preparation of highly active photocatalysts was developed. The protocol involves the preparation of a photocatalyst through the direct injection of metal alkoxide precursors into solutions in a photoreactor. As a proof of concept, a tantalum oxide based photocatalyst was chosen as a model system. Tantalum ethoxide [Ta(OEt)5 ] was injected rapidly into a photoreactor filled with a water/methanol mixture, and a TaOx (OH)y composite formed and was able to produce hydrogen under light illumination. Compared to commercial and mesostructured Ta2 O5 and NaTaO3 materials, TaOx (OH)y produced by direct injection shows superior hydrogen production activity. Notably, the samples prepared by direct injection are amorphous; however, their photocatalytic performance is much higher than those of their crystalline equivalents. If Ta(OEt)5 was dispersed in methanol before injection, an amorphous framework with higher surface area and larger pore volume was formed, and the hydrogen production rate increased further. The addition of a sodium precursor during the injection further boosted the photocatalytic activity. Furthermore, this concept has also been applied to a titanium-based photocatalyst, and a much better hydrogen production rate has been obtained in comparison with that of commercial TiO2 (P25-Degussa); therefore, the direct-injection synthesis is a flexible method that opens the door to the facile preparation of highly active nanostructured photocatalysts for hydrogen production. PMID- 26261011 TI - A molecular dynamics test of the Hertz-Knudsen equation for evaporating liquids. AB - The precise determination of evaporation flux from liquid surfaces gives control over evaporation-driven self-assembly in soft matter systems. The Hertz-Knudsen (HK) equation is commonly used to predict evaporation flux. This equation states that the flux is proportional to the difference between the pressure in the system and the equilibrium pressure for liquid/vapor coexistence. We applied molecular dynamics (MD) simulations of one component Lennard-Jones (LJ) fluid to test the HK equation for a wide range of thermodynamic parameters covering more than one order of magnitude in the values of flux. The flux determined in the simulations was 3.6 times larger than that computed from the HK equation. However, the flux was constant over time while the pressures in the HK equation exhibited strong fluctuations during simulations. This observation suggests that the HK equation may not appropriately grasp the physical mechanism of evaporation. We discuss this issue in the context of momentum flux during evaporation and mechanical equilibrium in this process. Most probably the process of evaporation is driven by a tiny difference between the liquid pressure and the gas pressure. This difference is equal to the momentum flux i.e. momentum carried by the molecules leaving the surface of the liquid during evaporation. The average velocity in the evaporation flux is very small (two to three orders of magnitude smaller than the typical velocity of LJ atoms). Therefore the distribution of velocities of LJ atoms does not deviate from the Maxwell Boltzmann distribution, even in the interfacial region. PMID- 26261008 TI - Prostaglandin E2 Promotes Colorectal Cancer Stem Cell Expansion and Metastasis in Mice. AB - BACKGROUND & AIMS: Inflammation may contribute to the formation, maintenance, and expansion of cancer stem cells (CSCs), which have the capacity for self-renewal, differentiation, and resistance to cytotoxic agents. We investigated the effects of the inflammatory mediator prostaglandin E2 (PGE2) on colorectal CSC development and metastasis in mice and the correlation between levels of PGE2 and CSC markers in human colorectal cancer (CRC) specimens. METHODS: Colorectal carcinoma specimens and matched normal tissues were collected from patients at the Mayo Clinic (Scottsdale, AZ) and analyzed by mass spectrometry and quantitative polymerase chain reaction. Human primary CRC cells and mouse tumor cells were isolated using microbeads or flow cytometry and analyzed for sphere formation and by flow cytometry assays. LS-174T cells were sorted by flow cytometry (for CD133(+)CD44(+) and CD133(-)CD44(-) cells) and also used in these assays. NOD-scidIL-2Rgamma(-/-) (NSG) mice were given cecal or subcutaneous injections of LS-174T or human primary CRC cells. Apc(Min/+) mice and NSG mice with orthotopic cecal tumors were given vehicle (controls), PGE2, celecoxib, and/or Ono-AE3-208. PGE2 downstream signaling pathways were knocked down with small hairpin RNAs, expressed from lentiviral vectors in LS-174T cells, or blocked with inhibitors in human primary CRC cells. RESULTS: Levels of PGE2 correlated with colonic CSC markers (CD133, CD44, LRG5, and SOX2 messenger RNAs) in human colorectal carcinoma samples. Administration of PGE2 to Apc(Min/+) mice increased tumor stem cells and tumor burden, compared with controls. NSG mice given PGE2 had increased numbers of cecal CSCs and liver metastases compared with controls after intracecal injection of LS-174T or human primary CRC cells. Alternatively, celecoxib, an inhibitor of prostaglandin-endoperoxide synthase 2, reduced polyp numbers in Apc(Min/+) mice, liver metastasis in NSG mice with orthotopic tumors, and numbers of CSCs in Apc(Min/+) and NSG mice. Inhibitors or knockdown of PGE2 receptor 4 (EP4), phosphoinositide 3-kinase (PI3K) p85alpha, extracellular signal-regulated kinase 1 (ERK1), or nuclear factor (NF)-kappaB reduced PGE2-induced sphere formation and expansion of LS-174T and/or human primary CRC cells. Knockdown of ERK1 or PI3K p85alpha also attenuated PGE2 induced activation of NF-kappaB in LS-174T cells. An EP4 antagonist reduced the ability of PGE2 to induce CSC expansion in orthotopic tumors and to accelerate the formation of liver metastases. Knockdown experiments showed that NF-kappaB was required for PGE2 induction of CSCs and metastasis in mice. CONCLUSIONS: PGE2 induces CSC expansion by activating NF-kappaB, via EP4-PI3K and EP4-mitogen activated protein kinase signaling, and promotes the formation of liver metastases in mice. The PGE2 signaling pathway therefore might be targeted therapeutically to slow CSC expansion and colorectal cancer progression. PMID- 26261009 TI - Development and Validation of a Scoring System to Predict Outcomes of Patients With Primary Biliary Cirrhosis Receiving Ursodeoxycholic Acid Therapy. AB - BACKGROUND & AIMS: Approaches to risk stratification for patients with primary biliary cirrhosis (PBC) are limited, single-center based, and often dichotomous. We aimed to develop and validate a better model for determining prognoses of patients with PBC. METHODS: We performed an international, multicenter meta analysis of 4119 patients with PBC treated with ursodeoxycholic acid at liver centers in 8 European and North American countries. Patients were randomly assigned to derivation (n = 2488 [60%]) and validation cohorts (n = 1631 [40%]). A risk score (GLOBE score) to predict transplantation-free survival was developed and validated with univariate and multivariable Cox regression analyses using clinical and biochemical variables obtained after 1 year of ursodeoxycholic acid therapy. Risk score outcomes were compared with the survival of age-, sex-, and calendar time-matched members of the general population. The prognostic ability of the GLOBE score was evaluated alongside those of the Barcelona, Paris-1, Rotterdam, Toronto, and Paris-2 criteria. RESULTS: Age (hazard ratio = 1.05; 95% confidence interval [CI]: 1.04-1.06; P < .0001); levels of bilirubin (hazard ratio = 2.56; 95% CI: 2.22-2.95; P < .0001), albumin (hazard ratio = 0.10; 95% CI: 0.05-0.24; P < .0001), and alkaline phosphatase (hazard ratio = 1.40; 95% CI: 1.18-1.67; P = .0002); and platelet count (hazard ratio/10 units decrease = 0.97; 95% CI: 0.96-0.99; P < .0001) were all independently associated with death or liver transplantation (C-statistic derivation, 0.81; 95% CI: 0.79-0.83, and validation cohort, 0.82; 95% CI: 0.79-0.84). Patients with risk scores >0.30 had significantly shorter times of transplant-free survival than matched healthy individuals (P < .0001). The GLOBE score identified patients who would survive for 5 years and 10 years (responders) with positive predictive values of 98% and 88%, respectively. Up to 22% and 21% of events and nonevents, respectively, 10 years after initiation of treatment were correctly reclassified in comparison with earlier proposed criteria. In subgroups of patients aged <45, 45-52, 52-58, 58-66, and >=66 years, age-specific GLOBE-score thresholds beyond which survival significantly deviated from matched healthy individuals were -0.52, 0.01, 0.60, 1.01 and 1.69, respectively. Transplant-free survival could still be accurately calculated by the GLOBE score with laboratory values collected at 2-5 years after treatment. CONCLUSIONS: We developed and validated scoring system (the GLOBE score) to predict transplant-free survival of ursodeoxycholic acid-treated patients with PBC. This score might be used to select strategies for treatment and care. PMID- 26261012 TI - Screw augmentation for spinopelvic fixation in neuromuscular spine deformities: technical note. AB - PURPOSE: The primary goal of curve correction in neuromuscular patients is to restore coronal and sagittal trunk balance, including the pelvis, to maximize sitting balance. For several years, it has been a common practice to inject polymeric cement into osteoporotic bone through specially designed, perforated pedicle screws in an effort to enhance screw stability. Therefore, we started using the association of a spinopelvic fixation with S1 pedicle screw augmentation, using bisphenol-a-glycidyl dimethacrylate composite resin in neuromuscular patients with pelvic obliquity, technique in neuromuscular patients to improve pedicle screw stability of our pelvic construct. METHODS: Ten patients undergoing spinopelvic fixation for a neuromuscular spinal deformity were enrolled in the study. Clinical and radiographic data were analyzed and presented. Minimal follow-up took place at 6 months to assess early complications. RESULTS: Five patients were diagnosed with spastic quadriplegia secondary to cerebral palsy, four had Duchenne's muscular dystrophy, and one had a T5-level traumatic flaccid paraplegia. Preoperative PO ranged from 8 degrees to 34 degrees (mean 19.16 degrees ). Postoperative PO ranged from 0 degrees to 6.3 degrees (mean 1.6 degrees ). After surgery, all patients returned to a full time sitting position between days 5 and 12 without the need for additional bracing. No mechanical failure of the construct was noted during follow-up. CONCLUSIONS: We used sacral pedicle screw augmentation as a reliable tool to strengthen spinopelvic fixation in neuromuscular scoliosis without increasing the intraoperative morbidity. In our practice, sacral screw augmentation can definitely enhance PO correction obtained by a posterior procedure. PMID- 26261014 TI - Letter to the Editor concerning "The validity and reliability of "Spinal Mouse" assessment of spinal curvatures in the frontal plane in pediatric adolescent idiopathic thoraco-lumbar curves" by Livanelioglu A, Kaya F, Nabiyev V, Demirkiran G, Firat T (2015) Eur Spine J Apr 22 [Epub ahead of print]. PMID- 26261013 TI - Interplay between low plasma RANKL and VDR-FokI polymorphism in lumbar disc herniation independently from age, body mass, and environmental factors: a case control study in the Italian population. AB - PURPOSE: Aim of this study was to investigate RANKL and osteoprotegerin plasma concentrations in patients affected by disc herniation, the most common epiphenomenon of disc degenerative diseases, and in a matched cohort of healthy subjects and whether the expression of these markers was associated to a polymorphism of the vitamin D receptor gene. METHODS: For this case-control study, 110 consecutive cases affected by lumbar disc herniation (confirmed by MRI) and 110 healthy age- and sex-matched controls were enrolled. Subjects affected by any other pathology were excluded. RANKL and osteoprotegerin were measured in plasma by immunoassays. The difference in these markers between cases and controls was assessed by t test. The correlation between osteoimmunological markers concentrations, anthropometrical variables, and the expression of the pathology was statistically assessed (Pearson's test) along with the association (Fisher's exact test) with the vitamin D receptor gene genotype, determined elsewhere. RESULTS: Despite comparable osteoprotegerin concentrations, cases, altogether or grouped for gender, express lower RANKL and, consequently, RANKL-to osteoprotegerin ratio. While in cases RANKL and osteoprotegerin concentrations were independent from age and BMI, in controls they increased with age. Disc herniation was strongly associated with RANKL and the presence of the F allele of the VDR gene. CONCLUSIONS: Whether vertebral bone changes precede or follow cartilage deterioration in intervertebral disc degeneration is not known. Our results suggest a reduced bone turnover rate, associated to a specific genetic background, in patients affected by lumbar disc herniation which could be one of the favoring factors for disc degeneration. PMID- 26261015 TI - Clinical findings of conservative cases with a coronally oriented vertical fracture of the posterior region of the C2 vertebral body. AB - PURPOSE: This report describes the characteristics of conservative cases with a coronally oriented vertical fracture of the posterior region of the C2 vertebral body. METHODS: Eight consecutive patients with a coronally oriented vertical fracture of the posterior region of the axis body who received conservative treatment were retrospectively reviewed. All the patients were male. The average patient age at injury was 71.4 years. The medical records of the patients were reviewed, and we identified the fractures associated with the cervical spine, other associated spinal fractures and the details of conservative treatment. RESULTS: Six patients had associated cervical spinal fractures, such as Jefferson fractures in four cases, spinous process fractures of the lower cervical spine in two cases, a teardrop fracture in one case and a unilateral spinous process fracture of C2 in one case. Two patients had associated spinal fractures in the thoracic spine. All the patients acquire solid bony fusion, including fusion of the associated cervical spinal fractures. CONCLUSIONS: The patients with a coronally oriented vertical fracture of the posterior region of the C2 vertebral body consisted were all elderly males in our study. Six of the eight patients demonstrated associated cervical spinal fractures; however, all patients acquired solid bony union, including fusion of the associated cervical spinal fractures. We suggest that a Philadelphia collar may be sufficient for conservatively treating coronally oriented vertical C2 body fractures, including associated cervical spinal fractures. PMID- 26261016 TI - Consumer opinion on social policy approaches to promoting positive body image: Airbrushed media images and disclaimer labels. AB - Disclaimer labels on airbrushed media images have generated political attention and advocacy as a social policy approach to promoting positive body image. Experimental research suggests that labelling is ineffective and consumers' viewpoints have been overlooked. A mixed-method study explored British consumers' ( N = 1555, aged 11-78 years) opinions on body image and social policy approaches. Thematic analysis indicated scepticism about the effectiveness of labelling images. Quantitatively, adults, although not adolescents, reported that labelling was unlikely to improve body image. Appearance diversity in media and reorienting social norms from appearance to function and health were perceived as effective strategies. Social policy and research implications are discussed. PMID- 26261017 TI - Television advertising, not viewing, is associated with negative dietary patterns in children. AB - BACKGROUND: Children's exposure to unhealthy food marketing is a contributor to poor diets and weight gain. Television food advertising, in particular, has been the focus of research and policy discussions. OBJECTIVES: We aimed to quantify the specific impact of television advertising, as distinct from television viewing generally, on children's usual diet. Methods Four hundred seventeen Australian children aged 10-16 participated in an online survey, which assessed television viewing habits and consumption of 12 frequently advertised unhealthy foods/drinks. Consumption of these foods/drinks was dichotomized (less weekly, weekly or more) and summed (1 point for each item consumed weekly or more) to give cumulative consumption scores. RESULTS: After adjusting for age and socioeconomic status, there was strong evidence of an increase in unhealthy food score (P < 0.001), drink score (P = 0.002) and food/drink combined score (P < 0.001), with increasing commercial television viewing. CONCLUSIONS: The link between television viewing and poor diet was strongest for children who watched the most commercial television, and those who were actually exposed to advertisements embedded within programs. This association between advertisement exposure and poor diet emphasizes the need for public policy intervention to reduce children's food advertising exposures. PMID- 26261018 TI - Disruption of glucocorticoid receptors in the noradrenergic system leads to BDNF up-regulation and altered serotonergic transmission associated with a depressive like phenotype in female GR(DBHCre) mice. AB - Recently, we have demonstrated that conditional inactivation of glucocorticoid receptors (GRs) in the noradrenergic system, may evoke depressive-like behavior in female but not male mutant mice (GR(DBHCre) mice). The aim of the current study was to dissect how selective ablation of glucocorticoid signaling in the noradrenergic system influences the previously reported depressive-like phenotype and whether it might be linked to neurotrophic alterations or secondary changes in the serotonergic system. We demonstrated that selective depletion of GRs enhances brain derived neurotrophic factor (BDNF) expression in female but not male GR(DBHCre) mice on both the mRNA and protein levels. The possible impact of the mutation on brain noradrenergic and serotonergic systems was addressed by investigating the tissue neurotransmitter levels under basal conditions and after acute restraint stress. The findings indicated a stress-provoked differential response in tissue noradrenaline content in the GR(DBHCre) female but not male mutant mice. An analogous gender-specific effect was identified in the diminished content of 5-hydroxyindoleacetic acid, the main metabolite of serotonin, in the prefrontal cortex, which suggests down-regulation of this monoamine system in female GR(DBHCre) mice. The lack of GR also resulted in an up-regulation of alpha2-adrenergic receptor (alpha2-AR) density in the female but not male mutants in the locus coeruleus. We have also confirmed the utility of the investigated model in pharmacological studies, which demonstrates that the depressive-like phenotype of GR(DBHCre) female mice can be reversed by antidepressant treatment with desipramine or fluoxetine, with the latter drug evoking more pronounced effects. Overall, our study validates the use of female GR(DBHCre) mice as an interesting and novel genetic tool for the investigation of the cross-connected mechanisms of depression that is not only based on behavioral phenotypes. PMID- 26261019 TI - N-acetylcysteine prevents stress-induced anxiety behavior in zebrafish. AB - Despite the recent advances in understanding the pathophysiology of anxiety disorders, the pharmacological treatments currently available are limited in efficacy and induce serious side effects. A possible strategy to achieve clinical benefits is drug repurposing, i.e., discovery of novel applications for old drugs, bringing new treatment options to the market and to the patients who need them. N-acetylcysteine (NAC), a commonly used mucolytic and paracetamol antidote, has emerged as a promising molecule for the treatment of several neuropsychiatric disorders. The mechanism of action of this drug is complex, and involves modulation of antioxidant, inflammatory, neurotrophic and glutamate pathways. Here we evaluated the effects of NAC on behavioral parameters relevant to anxiety in zebrafish. NAC did not alter behavioral parameters in the novel tank test, prevented the anxiety-like behaviors induced by an acute stressor (net chasing), and increased the time zebrafish spent in the lit side in the light/dark test. These data may indicate that NAC presents an anti-stress effect, with the potential to prevent stress-induced psychiatric disorders such as anxiety and depression. The considerable homology between mammalian and zebrafish genomes invests the current data with translational validity for the further clinical trials needed to substantiate the use of NAC in anxiety disorders. PMID- 26261020 TI - Small nuclear ribonucleoprotein associated polypeptide N accelerates cell proliferation in pancreatic adenocarcinoma. AB - The spliceosome, the large RNA-protein molecular complex, is crucial for pre-mRNA splicing. Several antitumor drugs have been found to tightly bind to the components of the spliceosome and mutations in the spliceosome have been reported in several types of cancer. However, the involvement of the spliceosome in pancreatic adenocarcinoma remains unclear. In the present study, small nuclear ribonucleoprotein associated polypeptide N (SNRPN), a key constituent of spliceosomes, was disrupted in BxPC-3 pancreatic adenocarcinoma cells using lentivirus-mediated RNA interference (RNAi). It was found that knockdown of SNRPN reduced the proliferation ability of BxPC-3 cells, as determined by an MTT assay. Furthermore, cell colony formation was impaired in SNRPN depleted adenocarcinoma cells and cell cycle analysis showed that depletion of SNRPN led to S phase cell cycle arrest and apoptosis. These results suggest that SNRPN is a key player in pancreatic adenocarcinoma cell growth, and targeted loss of SNRPN may be a potential therapeutic method for pancreatic cancer. PMID- 26261022 TI - The Effects of Limb Elevation on Muscle Oxygen Saturation: A Near-Infrared Spectroscopy Study in Humans. AB - BACKGROUND: Orthopaedic and rehabilitation physicians often instruct patients to elevate a traumatized or postoperative lower extremity. Elevation is thought to improve patient comfort, as well as decrease swelling, wound complications, and the risk of compartment syndrome. Elevating a limb with increased compartment pressures, however, has been shown to reduce perfusion pressure and contribute to tissue ischemia. This investigation aims to advance our understanding of the tissue effects of limb elevation using a healthy patient model. OBJECTIVE: To quantify the effects of elevation, experimentally induced ischemia, and immobilization on muscle oxygen saturation in the human leg using near-infrared spectroscopy (NIRS). DESIGN: Experimental crossover study. SETTING: Orthopaedic Surgery research laboratory, Stanford Hospitals & Clinics. PATIENTS FOR PARTICIPATION: Twenty-six healthy volunteers. METHODS: Using transcutaneous sensors, we measured muscle oxygen saturation of the anterior compartment of the left (control) leg at 0, 15, and 30 cm of elevation relative to the heart using NIRS. A standardized short leg splint and a thigh tourniquet inflated to 50 mmHg were then applied to the right (experimental) leg to simulate a traumatized state. NIRS measurements were then repeated, again at 0, 15, and 30 cm of elevation. Muscle oxygen saturation values at various degrees of elevation of the control and experimental limb were then compared and analyzed by the use of a crossover study design and mixed-effects regression. MAIN OUTCOME MEASUREMENTS: Muscle oxygen saturation at varying levels of elevation in both the (1) control leg and (2) experimental leg in a simulated traumatic state. RESULTS: Male (18) males and female (8) patients between 22 and 62 years of age (mean 29.8 years) were enrolled. Mean regional muscle oxygen saturation (rSO2) of the control limbs at 0, 15 and, 30 cm of elevation were 74.2%, 72.5%, and 70.6%, respectively, whereas mean rSO2 of the experimental limbs were 66.3%, 65.0%, and 63.3%. A statistically significant decrease of rSO2 was observed (mean 7.65%) in the experimental limbs compared with the control limbs. As elevation increased, there was a statistically significant decrease in rSO2 of 0.12% per centimeter of elevation. Elevation did not decrease the rSO2 in the experimental limb to a greater degree than in the control limb. CONCLUSION: Increasing levels of elevation in a human limb results in progressively compromised muscle oxygen saturation as measured by NIR. PMID- 26261021 TI - PfeT, a P1B4 -type ATPase, effluxes ferrous iron and protects Bacillus subtilis against iron intoxication. AB - Iron is an essential element for nearly all cells and limited iron availability often restricts growth. However, excess iron can also be deleterious, particularly when cells expressing high affinity iron uptake systems transition to iron rich environments. Bacillus subtilis expresses numerous iron importers, but iron efflux has not been reported. Here, we describe the B. subtilis PfeT protein (formerly YkvW/ZosA) as a P1B4 -type ATPase in the PerR regulon that serves as an Fe(II) efflux pump and protects cells against iron intoxication. Iron and manganese homeostasis in B. subtilis are closely intertwined: a pfeT mutant is iron sensitive, and this sensitivity can be suppressed by low levels of Mn(II). Conversely, a pfeT mutant is more resistant to Mn(II) overload. In vitro, the PfeT ATPase is activated by both Fe(II) and Co(II), although only Fe(II) efflux is physiologically relevant in wild-type cells, and null mutants accumulate elevated levels of intracellular iron. Genetic studies indicate that PfeT together with the ferric uptake repressor (Fur) cooperate to prevent iron intoxication, with iron sequestration by the MrgA mini-ferritin playing a secondary role. Protection against iron toxicity may also be a key role for related P1B4 -type ATPases previously implicated in bacterial pathogenesis. PMID- 26261023 TI - A Clinical Comparative Study of Ultrasound-Normal Versus Ultrasound-Abnormal Congenital Muscular Torticollis. AB - OBJECTIVE: To investigate the clinical features and outcome of outpatient-based physiotherapy (manual stretch) of congenital muscular torticollis (CMT) with passive neck motion limitation (>= 10 degrees ) according to whether the finding on ultrasonography (US) is normal or abnormal. DESIGN: Case-control study. SETTING: Institutional practice. PARTICIPANTS: A total of 149 patients with CMT who met eligibility criteria were included: age at presentation <= 6 months, limitation of passive neck rotation (DeltaROT) or lateral flexion (DeltaLAT) >= 10 degrees , and completion of our outpatient-based physiotherapy program. INTERVENTIONS: Patients were allocated to the US-normal or US-abnormal group. Patients underwent physiotherapy and were followed-up monthly until DeltaROT and DeltaLAT were <= 5 degrees or did not respond to treatment. MAIN OUTCOME MEASUREMENTS: Baseline characteristics, initial DeltaROT and DeltaLAT, age at presentation, treatment durations, and success rates of physiotherapy were compared between 2 groups. Treatment duration was adjusted for initial DeltaROT, DeltaLAT, and age at presentation using analysis of covariance. RESULTS: Mean initial DeltaROT and DeltaLAT in US-abnormal (28.5 degrees ; 17.0 degrees ) were greater than in US-normal (7.9 degrees , P < .001; 12.3 degrees , P = .001, respectively). Mean age at presentation was older in US-normal (3.8 months) than in US-abnormal (1.8 months, P < .001). Treatment duration was shorter in the US normal (5.1 weeks) than US-abnormal (14.9 weeks, P < .001). Adjusted treatment duration was also shorter in US-normal (9.7 weeks) than US-abnormal (13.8 weeks, P < .05). The success rates of physiotherapy were 95% in US-abnormal and 100% in US-normal. Two of 6 treatment failures in the US-abnormal group underwent surgery. CONCLUSIONS: In CMT with passive neck motion limitation (>= 10 degrees ), patients in the US-normal group demonstrated lesser passive neck motion limitation and older age at presentation than US-abnormal. It seems that US normal showed shorter treatment duration irrespective of severity of neck motion limitation and age at presentation. Additionally, manual stretching applied before 6 months of age appears to show generally good outcome regardless of US findings. PMID- 26261024 TI - Sonoelastographic Assessment of the Median Nerve in the Longitudinal Plane for Carpal Tunnel Syndrome. PMID- 26261025 TI - Vertebral Benign Notochordal Cell Tumor (BNCT) as an Incidental Finding in Cervical Radiculitis. PMID- 26261026 TI - An RNA-Seq-based reference transcriptome for Citrus. AB - Previous RNA-Seq studies in citrus have been focused on physiological processes relevant to fruit quality and productivity of the major species, especially sweet orange. Less attention has been paid to vegetative or reproductive tissues, while most Citrus species have never been analysed. In this work, we characterized the transcriptome of vegetative and reproductive tissues from 12 Citrus species from all main phylogenetic groups. Our aims were to acquire a complete view of the citrus transcriptome landscape, to improve previous functional annotations and to obtain genetic markers associated with genes of agronomic interest. 28 samples were used for RNA-Seq analysis, obtained from 12 Citrus species: C. medica, C. aurantifolia, C. limon, C. bergamia, C. clementina, C. deliciosa, C. reshni, C. maxima, C. paradisi, C. aurantium, C. sinensis and Poncirus trifoliata. Four different organs were analysed: root, phloem, leaf and flower. A total of 3421 million Illumina reads were produced and mapped against the reference C. clementina genome sequence. Transcript discovery pipeline revealed 3326 new genes, the number of genes with alternative splicing was increased to 19,739, and a total of 73,797 transcripts were identified. Differential expression studies between the four tissues showed that gene expression is overall related to the physiological function of the specific organs above any other variable. Variants discovery analysis revealed the presence of indels and SNPs in genes associated with fruit quality and productivity. Pivotal pathways in citrus such as those of flavonoids, flavonols, ethylene and auxin were also analysed in detail. PMID- 26261027 TI - Premolar root and canal variation in extant non-human hominoidea. AB - OBJECTIVES: The premolar sub-cervical region in four non-human extant ape genera are examined to: 1) define a classification scheme for the premolar root system in order to rigorously characterize, quantify and document variation in root and canal, form, number and configuration; 2) compare this variation within and between genera; and 3) test the hypotheses that sex and size (i.e., the "size/number continuum," Shields, ) of the premolar are determinants of root/canal form and/or number. MATERIALS AND METHODS: Microtomography and 3D visualization software are utilized to examine a large sample of Hylobates, Pan, Gorilla, and Pongo (n = 951 teeth). Each premolar root system is examined to ascertain the expected level of variability for each taxon. Cervical surface area (mm2 ) serves as a metric proxy for tooth size. A Chi-square test of independence is used to assess for variability differences between and within each taxon, and Mann-Whitney U tests are employed to assess the predicted relationship between tooth size and variation within each taxon. RESULTS: Our findings indicate that root and canal configurations, non-metric root traits and tooth size can distinguish between extant ape genera. Within the four ape taxa, premolar size variation is generally, but not always, correlated with canal/root number. Our results indicate that males and females within genera differ in tooth size but not in canal/root form and number. DISCUSSION: We report previously undocumented variation in the study taxa. Our results are discussed within the context of Miocene Apes as well as the developmental and systematic implications. Am J Phys Anthropol 158:209-226, 2015. (c) 2015 Wiley Periodicals, Inc. PMID- 26261028 TI - Costal cartilage elasticity can be estimated non-destructively using speed of sound. PMID- 26261029 TI - N-Heterocyclic Carbene Catalyzed Synthesis of delta-Sultones via alpha,beta Unsaturated Sulfonyl Azolium Intermediates. AB - A limited array of reactive intermediates have enabled a wealth of discoveries in N-heterocyclic carbene organocatalysis. In this study, the viability of alpha,beta-unsaturated sulfonyl azoliums as double electrophiles in new reactions is examined. Specifically, the (3+3) annulation of such species with the trimethylsilyl enol ethers of various 1,3-dicarbonyl compounds has been developed. This reaction provides access to a range of novel unsaturated delta sultones (18 examples) in good yields (40-88 %) under mild reaction conditions. Mechanistic studies and the development of an enantioselective variant (55 % yield, 73:27 e.r.) support the intermediacy of an alpha,beta-unsaturated sulfonyl azolium species. PMID- 26261030 TI - Left ventricular free wall perforation and left atrial dissection: unusual complication of radiofrequency catheter ablation for Wolf-Parkinson-White syndrome. AB - A 70-year-old woman with Wolf-Parkinson-White syndrome developed cardiac tamponade while undergoing radiofrequency catheter ablation for left posterolateral accessory pathway from the ventricular side below the mitral valve, requiring emergency surgery. During surgery, the patient was found to have perforation of the left posterior free wall as well as left atrial dissection. The patient died despite emergency measures. This case was remarkable because radiofrequency catheter ablation resulted in two very rare complications occurring at the same time in a patient. PMID- 26261031 TI - Analysis of the core genome and pangenome of Pseudomonas putida. AB - Pseudomonas putida are strict aerobes that proliferate in a range of temperate niches and are of interest for environmental applications due to their capacity to degrade pollutants and ability to promote plant growth. Furthermore solvent tolerant strains are useful for biosynthesis of added-value chemicals. We present a comprehensive comparative analysis of nine strains and the first characterization of the Pseudomonas putida pangenome. The core genome of P. putida comprises approximately 3386 genes. The most abundant genes within the core genome are those that encode nutrient transporters. Other conserved genes include those for central carbon metabolism through the Entner-Doudoroff pathway, the pentose phosphate cycle, arginine and proline metabolism, and pathways for degradation of aromatic chemicals. Genes that encode transporters, enzymes and regulators for amino acid metabolism (synthesis and degradation) are all part of the core genome, as well as various electron transporters, which enable aerobic metabolism under different oxygen regimes. Within the core genome are 30 genes for flagella biosynthesis and 12 key genes for biofilm formation. Pseudomonas putida strains share 85% of the coding regions with Pseudomonas aeruginosa; however, in P. putida, virulence factors such as exotoxins and type III secretion systems are absent. PMID- 26261034 TI - Association between thyroid-stimulating hormone and blood pressure in adults: an 11-year longitudinal study. AB - BACKGROUND: The results of longitudinal studies on the association between thyroid function and blood pressure (BP) are divided. This study aimed to investigate this association in cross-sectional and longitudinal settings in a nationwide, random sample representative of the Finnish adult population aged 30 and over. METHODS: The study sample was randomly drawn from the population register. A total of 5655 participants were included in the baseline analyses and 3453 in the 11-year prospective analyses. The associations between baseline TSH and (i) BP and BP change over time; and (ii) prevalent and incident hypertension were assessed using linear and logistic models, adjusted for age, gender, smoking and body mass index. RESULTS: A positive association (beta +/- standard error) was observed between TSH and diastolic (0.36 +/- 0.12, P = 0.003) but not systolic BP (0.16 +/- 0.21, P = 0.45) at baseline. TSH was negatively associated with 11-year BP change in men (systolic: -0.92 +/- 0.41, P = 0.03; diastolic: 0.66 +/- 0.26, P = 0.01) but not in women (P >= 0.09 for systolic and diastolic BP change). Participants in the highest TSH tertile within the TSH reference interval (0.4-3.4 mU/L), as compared with the lowest, had increased odds of prevalent (odds ratio 1.22, 95% confidence interval 1.05-1.43, P = 0.01) but not incident hypertension (odds ratio 0.93, 95% confidence interval 0.73-1.19, P = 0.58). CONCLUSIONS: A modest association was found between increasing TSH and prevalent but not incident hypertension. TSH was inversely associated with BP change in men in our study. These findings contest an independent role of thyroid function at normal to near-normal levels in the pathogenesis of hypertension. PMID- 26261033 TI - Antisense-mediated reduction of proprotein convertase subtilisin/kexin type 9 (PCSK9): a first-in-human randomized, placebo-controlled trial. AB - AIMS: LDL-receptor expression is inhibited by the protease proprotein convertase subtilisin/kexin type 9 (PCSK9), which is considered a pharmacological target to reduce LDL-C concentrations in hypercholesterolaemic patients. We performed a first-in-human trial with SPC5001, a locked nucleic acid antisense inhibitor of PCSK9. METHODS: In this randomized, placebo-controlled trial, 24 healthy volunteers received three weekly subcutaneous administrations of SPC5001 (0.5, 1.5 or 5 mg kg(-1)) or placebo (SPC5001 : placebo ratio 6 : 2). End points were safety/tolerability, pharmacokinetics and efficacy of SPC5001. RESULTS: SPC5001 plasma exposure (AUC(0,24 h)) increased more than dose-proportionally. At 5 mg kg(-1), SPC5001 decreased target protein PCSK9 (day 15 to day 35: -49% vs. placebo, P < 0.0001), resulting in a reduction in LDL-C concentrations (maximal estimated difference at day 28 compared with placebo -0.72 mmol l(-1), 95% confidence interval - 1.24, -0.16 mmol l(-1); P < 0.01). SPC5001 treatment (5 mg kg(-1)) also decreased ApoB (P = 0.04) and increased ApoA1 (P = 0.05). SPC5001 administration dose-dependently induced mild to moderate injection site reactions in 44% of the subjects, and transient increases in serum creatinine of >=20 MUmol l(-1) (15%) over baseline with signs of renal tubular toxicity in four out of six subjects at the highest dose level. One subject developed biopsy-proven acute tubular necrosis. CONCLUSIONS: SPC5001 treatment dose-dependently inhibited PCSK9 and decreased LDL-C concentrations, demonstrating human proof-of-pharmacology. However, SPC5001 caused mild to moderate injection site reactions and renal tubular toxicity, and clinical development of SPC5001 was terminated. Our findings underline the need for better understanding of the molecular mechanisms behind the side effects of compounds such as SPC5001, and for sensitive and relevant renal toxicity monitoring in future oligonucleotide studies. PMID- 26261035 TI - Update on management of genitourinary syndrome of menopause: A practical guide. AB - The term genitourinary syndrome of menopause (GSM) emerged following a consensus conference held in May 2013. GSM is a more descriptive term than vulvovaginal atrophy (VVA) and does not imply pathology. However there are concerns that GSM is all encompassing and includes not only symptoms resulting from estrogen deficiency, but also those arising from the effects of ageing and other processes on the bladder and pelvic floor. Focusing on symptoms related to estrogen deficiency, the update provides a practical guide for health and allied health professionals on the impact of GSM on women and their partners, assessment, management and areas for future research. As GSM is a chronic condition, long term therapy is required. Hormonal, nonhormonal, laser and alternative and complementary therapies are described. PMID- 26261036 TI - From the Women's Health Initiative to the combination of estrogen and selective estrogen receptor modulators to avoid progestin addition. AB - The female life expectancy rose from an average of 48 years to over 80 years in a century. The decline in the endogenous production of estrogen (especially the main circulating physiological hormone, 17beta-estradiol, E2) at menopause (51 years on average) often leads to functional disorders affecting the quality of life. Estrogen deficiency impacts different tissues and results in an increase of various diseases, such as osteoporosis or cardiovascular diseases. Hormone therapy (HT) for menopause is a rather new challenge which experienced vagaries following the women's health initiative (WHI) study conducted in largely post menopausal women. In the first part of this review, we will try to summarize the main conclusions of the WHI trials, in particular the timing effect as well as the deleterious impact of the associated progestin, medroxyprogesterone acetate (MPA). Hormone therapy, particularly the conjugated equine estrogen (CEE) combined with the MPA favor the occurrence of breast cancer, whereas conversely selective estrogen receptor modulators (SERMs, such as tamoxifen or raloxifene) that block the activity of estrogen receptor alpha (ERa) prevent the risk of recurrence of ERa-positive breast cancers. A new strategy of ERa modulation called tissue selective estrogen complex (TSEC), combines (1) CEE to maintain the benefits of estrogen (climacteric symptoms and prevention of osteoporosis) and (2) bazedoxifene, which is not only a SERM, but which also induces a rapid degradation of ERa in the uterus and in the breast, thereby prevents the stimulatory effects of estrogens on epithelial proliferation of these two sex targets. In the second part of this review, we will summarize the recognized benefits of the TSEC approach, and our current knowledge of its potential benefits and risks. PMID- 26261037 TI - Eating disorders in older women. AB - Eating disorders (EDs) are disturbances that seriously endanger the physical health and often the lives of sufferers and affect their psychosocial functioning. EDs are usually thought of as problems afflicting teenagers. However, the incidence in older women has increased in recent decades. These cases may represent either late-onset disease or, more likely, a continuation of a lifelong disorder. The DSM-5 classification differentiates 4 categories of eating disorder: anorexia nervosa, bulimia nervosa, binge-eating disorders and other specified feeding and eating disorders. The weight loss and malnutrition resulting from EDs have widespread negative consequences for physical, mental and social health. The main risk factors for developing long-term consequences are the degree of weight loss and the chronicity of the illness. Most of the cardiac, neurological, pulmonary, gastric, haematological and dermatological complications of EDs are reversible with weight restoration. EDs are serious illnesses and they should never be neglected or treated only as a manifestation of the fashion for dieting or a woman's wish to achieve an imposed standard feminine figure. Additionally, EDs are associated with high risk of morbidity and mortality. The literature concerning EDs in older, postmenopausal women is very limited. The main aim of this paper is to ascertain the epidemiology and prognosis of EDs in older women, and to review their diagnosis and management. PMID- 26261038 TI - Associations between obesity, physical fitness, and urinary incontinence in non institutionalized postmenopausal women: The elderly EXERNET multi-center study. AB - OBJECTIVES: To investigate the associations between body composition, fitness level, and urinary incontinence (UI) in 471 non-institutionalized women >= 65 years of age. STUDY DESIGN: Cross-sectional study. METHOD: UI was assessed using the International Consultation on Incontinence Questionnaire Short-Form and a specific severity UI item. Anthropometric measurements were obtained using standardized techniques and equipment. Body fat percentage (BF%) was measured by bioelectrical impedance. Physical fitness (PF) was evaluated by a set of 8 tests and a fitness index (FI) was calculated. Active and sedentary behaviors were recorded by standardized questionnaires. RESULTS: UI was reported in 28.5% of the participants. Women with UI showed higher values of body mass index (BMI), BF% and waist circumference (WC) (all p<0.05) compared to urinary continent women, whereas there was a lower fitness index (FI) level in women with UI (p=0.08). Among all fitness capacities, upper body flexibility showed the closest relationship with UI. UI risk increased by 87.0% [95% confidence intervals (1.01 3.17)] in obese women compared to the normal group, according to the BF% while no significant results were found when PF, WC and BMI were included in the model. Mean sitting and walking time per day were 4.3+/-1.4 and 1.8+/-0.9 h/d, respectively. CONCLUSION: UI was associated with an excess of fat mass and poor PF, especially upper-body flexibility. PMID- 26261040 TI - Exploring linkage disequilibrium. AB - Linkage disequilibrium (LD, association of allelic states across loci) is poorly understood by many evolutionary biologists, but as technology for multilocus sampling improves, we ignore LD at our peril. If we sample variation at 10 loci in an organism with 20 chromosomes, we can reasonably treat them as 10 'independent witnesses' of the evolutionary process. If instead, we sample variation at 1000 loci, many are bound to be close together on a chromosome. With only one or two crossovers per meiosis, associations between close neighbours decay so slowly that even LD created far in the past will not have dissipated, so we cannot treat the 1000 loci as independent witnesses (Barton ). This means that as marker density on genomes increases classic analyses assuming independent loci become mired in the problem of overconfidence: if 1000 independent witnesses are assumed, and that number should be much lower, any conclusion will be overconfident. This is of special concern because our literature suffers from a strong publication bias towards confident answers, even when they turn out to be wrong (Knowles ). In contrast, analyses that take into account associations across loci both control for overconfidence and can inform us about LD generating events far in the past, for example human/Neanderthal admixture (Fu et al. ). With increased marker density, biologists must increase their awareness of LD and, in this issue of Molecular Ecology Resources, Kemppainen et al. () make software available that can only help in this process: LDna allows patterns of LD in a data set to be explored using tools borrowed from network analysis. This has great potential, but realizing that potential requires understanding LD. PMID- 26261039 TI - Comparison of the gut microbiota composition between obese and non-obese individuals in a Japanese population, as analyzed by terminal restriction fragment length polymorphism and next-generation sequencing. AB - BACKGROUND: Obesity has become one of the most serious social problems in developed countries, including Japan. The relationship between the gut microbiota and obesity has recently attracted the attention of many researchers. Although the gut microbiota was long thought to contribute to obesity, the exact association remains largely unknown. We examined the human gut microbiota composition in a Japanese population in order to determine its relationship to obesity. METHODS: Stool samples from 23 non-obese subjects (body mass index [BMI] <20 kg/m(2)) and 33 obese subjects (BMI >=25 kg/m(2)) were collected and DNA was extracted prior to colonoscopy. After terminal restriction fragment length polymorphism (T-RFLP) analysis, samples from 10 subjects (4 non-obese and 6 obese) were selected and subjected to next-generation sequencing for species level analysis. RESULTS: T-RFLP analysis showed significantly reduced numbers of Bacteroidetes and a higher Firmicutes to Bacteroidetes ratio in obese subjects compared with non-obese subjects. Bacterial diversity was significantly greater in obese subjects compared with non-obese subjects. Next-generation sequencing revealed that obese and non-obese subjects had different gut microbiota compositions and that certain bacterial species were significantly associated with each group (obese: Blautia hydrogenotorophica, Coprococcus catus, Eubacterium ventriosum, Ruminococcus bromii, Ruminococcus obeum; non-obese: Bacteroides faecichinchillae, Bacteroides thetaiotaomicron, Blautia wexlerae, Clostridium bolteae, Flavonifractor plautii). CONCLUSION: Gut microbial properties differ between obese and non-obese subjects in Japan, suggesting that gut microbiota composition is related to obesity. PMID- 26261041 TI - Genomic Resources Notes accepted 1 April 2015 - 31 May 2015. AB - This article documents the public availability of transcriptomic resources for (i) the stellate sturgeon Acipenser stellatus, (ii) the flowering plant Campanula gentilis and (iii) two endemic Iberian fish, Squalius carolitertii and Squalius torgalensis. PMID- 26261042 TI - Analysis of the association between IL-23R rs11209026 polymorphism and incidence of atherosclerosis. AB - Th17/IL-23 axis is an important pro-inflammatory pathway in atherosclerosis. IL 23 receptor (IL-23R) pathway has an important role in T-helper cells 17 (Th17) differentiation and survival. We compared normal subjects and patients with atherosclerosis in terms of the R381Q variant of the IL-23R gene as a functional single-nucleotide polymorphism (SNP). This case-control study recruited 200 patients who presented with cardiovascular symptoms to Afshar Hospital, Yazd, Iran. The participants were allocated to five groups based on angiographic results. The severity of the disease was determined according to the numbers of involved vessels. Patients with normal coronary arteries, minimal coronary artery involvement, one involved vessel, two involved vessels and three-vessel disease were allocated to groups I-V, respectively. DNA was extracted from whole blood samples by the salting-out method. Genotyping was performed by polymerase chain reaction followed by restriction fragment length polymorphism assay and multinomial logistic regression for analyses The presence of SNP A>G rs11209026 of IL-23 receptor gene was significantly associated with disease severity (P = 0.008). The frequencies of the heterozygous (AG) genotype in the control group and subjects with minimal involvement, and patients with one-, two-, and three vessel disease were 22.5%, 12.5%, 10%, 10.24% and 4.8%, respectively. Our results indicated an association between the rs11209026 G>A polymorphism of the IL-23 receptor gene and the risk of atherosclerosis. This genetic variant may in fact cause protection against atherosclerosis progression. However, further studies on gene polymorphism and cell expression are required to clarify the mechanisms involved in the pathogenesis of atherosclerosis. PMID- 26261043 TI - Subcellular and Dynamic Coordination between Src Activity and Cell Protrusion in Microenvironment. AB - Migration of endothelial cells is essential for wound healing and angiogenesis. Src kinase activity plays important roles at the protrusions of migrating endothelial cells. However, the spatiotemporal coordination between Src kinase activity and the protrusion of cell edge remains unclear. Therefore, we investigate these coordinated molecular events at the initiation of cell migration, by integrating microfabrication, fluorescence resonance energy transfer (FRET)-based biosensors, and automated computational image analysis. We demonstrate that the physical release of restrictive micropattern triggered a significant decrease of Src activity at the protrusive edge of endothelial cells. Computational cross-correlation analysis reveals that the decrease of Src activity occurred earlier in time, and was well-coordinated with the protrusion of cell edge in polarized cells, but not in non-polarized cells. These results suggest that the spatiotemporal control of Src kinase activity is well coordinated with cell polarization and protrusion in endothelial cells upon the release of physical constraint, as that experienced by endothelial cells sprouting from stiff tumor micro-environment during angiogenesis. Therefore, our integrative approach enabled the discovery of a new model where Src is de activated in coordination with membrane protrusion, providing important insights into the regulation of endothelial migration and angiogenesis. PMID- 26261044 TI - Assessing Walking Activity in Older Adults: Development and Validation of a Novel Computer-Animated Assessment Tool. AB - BACKGROUND: Assessing volume of physical activity (PA) in older adults is critical to understanding the role that PA has on health outcomes and the effectiveness of treatment interventions to increase PA. The purpose of this study was to investigate the psychometric properties of a novel computer-animated self-report questionnaire designed to assess walking activity of older adults: the Mobility Assessment Tool for Walking--the MAT-W. METHODS: We recruited 249 older adults (66.9+/-4.7 years, 71% female, 32% black) with cardiovascular disease and/or metabolic syndrome as part of the Cooperative Lifestyle Intervention Program-II study. Participants completed the MAT-W at baseline and after 6 months of a walking and weight loss (n = 78) or weight loss only (n = 69) intervention. Test-retest reliability was assessed in 31 participants. Walking speed at usual and fast pace was measured using a GAITRite mat, and 7-day accelerometry data were collected at baseline and 6 months. The mCHAMPS5, a modified version of a widely used self-report PA questionnaire, was completed at baseline. RESULTS: The test-retest reliability of MAT-W was excellent (intraclass correlation coefficient > .85). The MAT-W was correlated with mCHAMPS5 (Spearman r = .66, p < .001) and moderate/vigorous levels of PA as assessed by accelerometry (Spearman r = .65, p < .001) and was responsive to an intervention induced change in PA at 6 months when comparing the Cooperative Lifestyle Intervention Program-II walking and weight loss group with the weight loss only group (p < .001). CONCLUSION: The MAT-W is a brief, reliable, and valid tool to assess PA and has promise for the assessment of walking behavior in older adults under free-living conditions. PMID- 26261045 TI - Twin Cavities: An Unusual Radiological Finding in Pulmonary Tuberculosis. PMID- 26261046 TI - Benefits of Mitral Valve Repair in Moderate Ischemic Mitral Regurgitation. PMID- 26261047 TI - Degradation of Kresoxim-Methyl in Water: Impact of Varying pH, Temperature, Light and Atmospheric CO2 Level. AB - In the present investigation, persistence of kresoxim-methyl (a broad spectrum strobilurin fungicide) was studied in water. Results revealed that kresoxim methyl readily form acid metabolite. Therefore, residues of kresoxim-methyl were quantified on the basis of parent molecule alone and sum total of kresoxim-methyl and its acid metabolite. In water, influence of various abiotic factors like pH, temperature, light and atmospheric carbon dioxide level on dissipation of kresoxim-methyl was studied. The half life value for kresoxim-methyl and total residue varied from 1 to 26.1 and 6.1 to 94.0 days under different conditions. Statistical analysis revealed the significant effect of abiotic factors on the dissipation of kresoxim-methyl from water. PMID- 26261048 TI - The dissipation of fipronil, chlorpyrifos, fosthiazate and ethoprophos in soils from potato monoculture areas: first evidence for the enhanced biodegradation of fosthiazate. AB - BACKGROUND: A limited number of pesticides are available for the control of soil pests in potato. This, together with the monoculture nature of potato cultivation, does not favour chemical rotation, increasing the risk of reduced biological efficacy due to microbial adaptation. The dissipation of three major organophosphates (chlorpyrifos, ethoprophos and fosthiazate) was studied in comparison with fipronil, an insecticide recently introduced in potato cultivation, in 17 soils from potato monoculture areas in Greece to explore the extent of enhanced biodegradation development. RESULTS: The dissipation time of the four pesticides varied in the different soils, with DT50 values of 1.7-30.8 days, 2.7-56 days, 7.0-31.0 days and 24.5-116.5 days for fosthiazate, chlorpyrifos, ethoprophos and fipronil, respectively. A rapid dissipation of ethoprophos and fosthiazate in two soils with previous exposure to these nematicides provided first evidence for the development of enhanced biodegradation. Sterilisation of the given soils inhibited the dissipation of fosthiazate. Additionally, fosthiazate dissipation in the soils increased upon repeated applications. CONCLUSION: The development of enhanced biodegradation of fosthiazate in soils from potato monoculture regions was verified. This is the first report of enhanced biodegradation for this chemical. Further studies will focus on the isolation of microorganisms responsible for the dissipation of fosthiazate. PMID- 26261050 TI - Molecular architectures and functions of radical enzymes and their (re)activating proteins. AB - Certain proteins utilize the high reactivity of radicals for catalysing chemically challenging reactions. These proteins contain or form a radical and therefore named 'radical enzymes'. Radicals are introduced by enzymes themselves or by (re)activating proteins called (re)activases. The X-ray structures of radical enzymes and their (re)activases revealed some structural features of these molecular apparatuses which solved common enigmas of radical enzymes-i.e. how the enzymes form or introduce radicals at the active sites, how they use the high reactivity of radicals for catalysis, how they suppress undesired side reactions of highly reactive radicals and how they are (re)activated when inactivated by extinction of radicals. This review highlights molecular architectures of radical B12 enzymes, radical SAM enzymes, tyrosyl radical enzymes, glycyl radical enzymes and their (re)activating proteins that support their functions. For generalization, comparisons of the recently reported structures of radical enzymes with those of canonical radical enzymes are summarized here. PMID- 26261049 TI - Frontiers in research on biodiversity and disease. AB - Global losses of biodiversity have galvanised efforts to understand how changes to communities affect ecological processes, including transmission of infectious pathogens. Here, we review recent research on diversity-disease relationships and identify future priorities. Growing evidence from experimental, observational and modelling studies indicates that biodiversity changes alter infection for a range of pathogens and through diverse mechanisms. Drawing upon lessons from the community ecology of free-living organisms, we illustrate how recent advances from biodiversity research generally can provide necessary theoretical foundations, inform experimental designs, and guide future research at the interface between infectious disease risk and changing ecological communities. Dilution effects are expected when ecological communities are nested and interactions between the pathogen and the most competent host group(s) persist or increase as biodiversity declines. To move beyond polarising debates about the generality of diversity effects and develop a predictive framework, we emphasise the need to identify how the effects of diversity vary with temporal and spatial scale, to explore how realistic patterns of community assembly affect transmission, and to use experimental studies to consider mechanisms beyond simple changes in host richness, including shifts in trophic structure, functional diversity and symbiont composition. PMID- 26261051 TI - Non-canonical WNT signalling in the lung. AB - The role of WNT signalling in metazoan organogenesis has been a topic of widespread interest. In the lung, while the role of canonical WNT signalling has been examined in some detail by multiple studies, the non-canonical WNT signalling has received limited attention. Reliable evidence shows that this important signalling mechanism constitutes a major regulatory pathway in lung development. In addition, accumulating evidence has also shown that the non canonical WNT pathway is critical for maintaining lung homeostasis and that aberrant activation of this pathway may underlie several debilitating lung diseases. Functional analyses have further revealed that the non-canonical WNT pathway regulates multiple cellular activities in the lung that are dependent on the specific cellular context. In most cell types, non-canonical WNT signalling regulates canonical WNT activity, which is also critical for many aspects of lung biology. This review will summarize what is currently known about the role of non canonical WNT signalling in lung development, homeostasis and pathogenesis of disease. PMID- 26261052 TI - Dental floss as a possible risk for the development of peri-implant disease: an observational study of 10 cases. AB - AIM: To report on a possible relationship between the use of dental floss or superfloss and the development of peri-implantitis. MATERIALS AND METHODS: Ten patients with progressive peri-implantitis with an intensive oral hygiene protocol, which consisted of extensive professional supra- and submucosal cleaning, and not responding to this therapy were scheduled for examination. Plaque and bleeding indices and probing depth measurements were assessed, and radiographic examination was performed every two years. RESULTS: In all ten cases, remnants of dental floss were found around the neck and coronal part of a dental implant. After careful removal of these floss remnants and implant cleansing, a significant improvement in the peri-implant conditions in nine of ten cases was noted. In one case, peri-implant probing depth decreased substantially. However, bleeding on probing was still present. In vitro testing yielded that the application of various types of dental floss on the exposed rough implant surfaces may easily lead to tearing of floss fibers. This may result in the deposition of floss remnants on rough implant surfaces, which, in turn, may lead to the development of plaque-related peri-implant inflammation and, subsequently, bone loss. CONCLUSION: In case of exposed rough surfaces of the dental implant, the peri-implant conditions may be jeopardized by the application of dental floss, and hence, the utilization of interproximal brushes or toothpicks may be preferred for daily home care practices. PMID- 26261053 TI - Geographic range did not confer resilience to extinction in terrestrial vertebrates at the end-Triassic crisis. AB - Rates of extinction vary greatly through geological time, with losses particularly concentrated in mass extinctions. Species duration at other times varies greatly, but the reasons for this are unclear. Geographical range correlates with lineage duration amongst marine invertebrates, but it is less clear how far this generality extends to other groups in other habitats. It is also unclear whether a wide geographical distribution makes groups more likely to survive mass extinctions. Here we test for extinction selectivity amongst terrestrial vertebrates across the end-Triassic event. We demonstrate that terrestrial vertebrate clades with larger geographical ranges were more resilient to extinction than those with smaller ranges throughout the Triassic and Jurassic. However, this relationship weakened with increasing proximity to the end-Triassic mass extinction, breaking down altogether across the event itself. We demonstrate that these findings are not a function of sampling biases; a perennial issue in studies of this kind. PMID- 26261054 TI - Hypothalamic carnitine metabolism integrates nutrient and hormonal feedback to regulate energy homeostasis. AB - The maintenance of energy homeostasis requires the hypothalamic integration of nutrient feedback cues, such as glucose, fatty acids, amino acids, and metabolic hormones such as insulin, leptin and ghrelin. Although hypothalamic neurons are critical to maintain energy homeostasis research efforts have focused on feedback mechanisms in isolation, such as glucose alone, fatty acids alone or single hormones. However this seems rather too simplistic considering the range of nutrient and endocrine changes associated with different metabolic states, such as starvation (negative energy balance) or diet-induced obesity (positive energy balance). In order to understand how neurons integrate multiple nutrient or hormonal signals, we need to identify and examine potential intracellular convergence points or common molecular targets that have the ability to sense glucose, fatty acids, amino acids and hormones. In this review, we focus on the role of carnitine metabolism in neurons regulating energy homeostasis. Hypothalamic carnitine metabolism represents a novel means for neurons to facilitate and control both nutrient and hormonal feedback. In terms of nutrient regulation, carnitine metabolism regulates hypothalamic fatty acid sensing through the actions of CPT1 and has an underappreciated role in glucose sensing since carnitine metabolism also buffers mitochondrial matrix levels of acetyl CoA, an allosteric inhibitor of pyruvate dehydrogenase and hence glucose metabolism. Studies also show that hypothalamic CPT1 activity also controls hormonal feedback. We hypothesis that hypothalamic carnitine metabolism represents a key molecular target that can concurrently integrate nutrient and hormonal information, which is critical to maintain energy homeostasis. We also suggest this is relevant to broader neuroendocrine research as it predicts that hormonal signaling in the brain varies depending on current nutrient status. Indeed, the metabolic action of ghrelin, leptin or insulin at POMC or NPY neurons may depend on appropriate nutrient-sensing in these neurons and we hypothesize carnitine metabolism is critical in the integrative processing. Future research is required to examine the neuron-specific effects of carnitine metabolism on concurrent nutrient- and hormonal-sensing in AgRP and POMC neurons. PMID- 26261055 TI - Animal models of spontaneous pancreatic neuroendocrine tumors. AB - Pancreatic neuroendocrine tumors (PNETs) are usually low-grade neoplasms derived from the endocrine pancreas. PNETs can be functioning and cause well-described hormonal hypersecretion syndromes or non-functioning and cause only tumor mass effect. PNETs appear to be more common recently likely due to incidental detection by imaging. Although the diagnosis and management of PNETs have been evolving rapidly, much remains to be studied in the areas of molecular pathogenesis, molecular markers of tumor behavior, early detection, and targeted drug therapy. Unique challenges facing PNETs studies are long disease course, the deep location of pancreas and difficult access to pancreatic tissue, and the variety of tumors, which make animal models valuable tools for PNETs studies. Existing animal models of PNETs have provided insights into the pathogenesis and natural history of human PNETs. Future studies on animal models of PNETs should address early tumor detection, molecular markers of tumor behavior, and novel targeted therapies. PMID- 26261056 TI - Pioglitazone treatment and cardiovascular event and death in subjects with type 2 diabetes without established cardiovascular disease (JDDM 36). AB - AIMS: The protective association of pioglitazone with cardiovascular events and death was investigated over 6-years in large-scale type 2 diabetic subjects without established cardiovascular disease in a primary care setting. METHODS: A six-year observational cohort study including 2864 subjects with type 2 diabetes without established cardiovascular disease was performed. The primary endpoint was a composite of first occurrence of cardiovascular disease or death. The effect of pioglitazone use at a baseline year with a Cox proportional hazard model and the time-dependent use in each one-year examination interval with a pooled logistic regression model were analyzed. RESULTS: Baseline use of pioglitazone (n=493) did not show a statistically protective effect on the primary endpoint (n=175), although it tended to reduce the risk (adjusted hazard ratio 0.67 [95% CI: 0.43-1.05]). However, pooled logistic regression analysis indicated a significant protective association of pioglitazone with the primary endpoint (0.58 [0.38 to 0.87] and cardiovascular disease (0.54 [0.33-0.88]), independent of concurrent levels of blood glucose, blood pressure, lipids, albuminuria, and renal function. In particular, this protective association was observed in those with diabetic nephropathy regardless of the daily dose of pioglitazone. Among a total of 898 subjects who took pioglitazone during the period, 43% experienced a discontinuation at least once; however, serious adverse effects were rare. CONCLUSIONS: This observational study indicated a protective association of pioglitazone with cardiovascular disease and death in type 2 diabetic subjects without established vascular disease, particularly those with nephropathy. PMID- 26261058 TI - Footwear in rock climbing: Current practice. AB - BACKGROUND: Many rock climbers wear ill-fitting and excessively tight footwear during activity. However, there is insufficient evidence of the extent or harms of this practice. OBJECTIVES: To investigate footwear use in rock climbers with a focus on issues surrounding fit. METHODS: A cross-sectional study with active rock climbers of over one year of experience completing a survey on their activity and footwear. Additionally, the authors quantified foot and shoe lengths and sizes alongside demographic data. RESULTS: Ill-fitting and excessively tight footwear was found in 55 out of 56 rock climbers. Foot pain during activity was also commonplace in 91% of the climbers. A mean size reduction of almost 4 UK shoe sizes was found between the climbers' street shoe size and that of their climbing footwear using a calibrated foot/shoe ruler. There is an unfortunate association of climbers of higher abilities seeking a tighter shoe fit (p<0.001). CONCLUSION: With the elucidation of footwear use amongst rock climbers, further investigation may aim to quantify its impact and seek a solution balancing climbing performance while mitigating foot injury. PMID- 26261057 TI - Characterization of anti-CD20 monoclonal antibody produced by transgenic silkworms (Bombyx mori). AB - In response to the successful use of monoclonal antibodies (mAbs) in the treatment of various diseases, systems for expressing recombinant mAbs using transgenic animals or plants have been widely developed. The silkworm (Bombyx mori) is a highly domesticated insect that has recently been used for the production of recombinant proteins. Because of their cost-effective breeding and relatively easy production scale-up, transgenic silkworms show great promise as a novel production system for mAbs. In this study, we established a transgenic silkworm stably expressing a human-mouse chimeric anti-CD20 mAb having the same amino acid sequence as rituximab, and compared its characteristics with rituximab produced by Chinese hamster ovary (CHO) cells (MabThera(r)). The anti-CD20 mAb produced in the transgenic silkworm showed a similar antigen-binding property, but stronger antibody-dependent cell-mediated cytotoxicity (ADCC) and weaker complement-dependent cytotoxicity (CDC) compared to MabThera. Post-translational modification analysis was performed by peptide mapping using liquid chromatography/mass spectrometry. There was a significant difference in the N glycosylation profile between the CHO- and the silkworm-derived mAbs, but not in other post-translational modifications including oxidation and deamidation. The mass spectra of the N-glycosylated peptide revealed that the observed biological properties were attributable to the characteristic N-glycan structures of the anti-CD20 mAbs produced in the transgenic silkworms, i.e., the lack of the core fucose and galactose at the non-reducing terminal. These results suggest that the transgenic silkworm may be a promising expression system for the tumor-targeting mAbs with higher ADCC activity. PMID- 26261059 TI - Two cases of erythema induratum of Bazin--a rare cutaneous manifestation of tuberculosis. AB - Tuberculosis remains a global disease burden, counting more than 9 million new cases per year. Tuberculosis is caused by infection with Mycobacterium tuberculosis-complex. Though most commonly affecting the lungs, any organ can become a site of tuberculous infection. Cutaneous tuberculosis is rare, representing 1-2% of all cases of tuberculosis. There are numerous different cutaneous manifestations of tuberculosis. We describe two cases of erythema induratum of Bazin, a so-called tuberculid manifestation of cutaneous TB. Both cases are patients from endemic areas. In the cases presented, there were no signs of other organs affected, and cutaneous lesions disappeared during anti tuberculous treatment. PMID- 26261060 TI - An association study of NRAMP1, VDR, MBL and their interaction with the susceptibility to tuberculosis in a Chinese population. AB - OBJECTIVES: To investigate natural-resistance-associated macrophage protein 1 (NRAMP1), mannose-binding lectin (MBL), vitamin D receptor (VDR) gene polymorphisms and their interaction with susceptibility to pulmonary tuberculosis (PTB) in a Chinese population. METHODS: A case-control study was conducted in PTB (n=151), age- and sex- matched healthy controls (HCs) (n=453). Genetic polymorphisms of NRAMP1 (INT4, D543NA and 3'UTR), MBL (HL, PQ, XY and AB) and VDR (FokI and Taq) were analyzed by using PCR-restriction fragment length polymorphism (RFLP) and PCR- single- strand conformation polymorphism (SSCP) techniques. Multifactor dimensionality reduction (MDR) analysis was carried out to assess the effects of the interaction between SNPs. RESULTS: The distribution of NRAMP1- 3'UTR (TGTG/del), MBL- HL (H/L) and FokI (F/f) were significantly different between PTB patients and HCs (p<0.05). HPYA (OR: 1.88; 95% CI: 1.22 2.91), LPXA (OR: 3.17; 95% CI: 1.69- 5.96), LQYA (OR: 3.52; 95%CI: 1.50-8.23) and LPYB (OR: 12.37; 95%CI: 3.75- 40.85) of MBL were risk haplotypes for PTB. The TGTG- H- f (OR: 1.70; 95%CI: 1.10-2.62) and del- H-f (OR: 3.48; 95% CI: 1.45 8.37) of 3'UTR- HL- FokI were also high-risk haplotypes associated with tuberculosis. CONCLUSIONS: Our study suggests that genotypes of many polymorphic genes are associated with TB, it is necessary to further explore the mechanism of genotypes and gene-gene interaction in susceptibility to tuberculosis. PMID- 26261061 TI - AGXT and ERCC2 polymorphisms are associated with clinical outcome in metastatic colorectal cancer patients treated with 5-FU/oxaliplatin. AB - The objective of the study was to investigate whether specific single nucleotide polymorphisms (SNPs) with influence on drug transport, biotransformation and repair mechanisms are associated with treatment outcome and toxicity in metastatic colorectal cancer (mCRC). We genotyped blood samples from 519 mCRC patients treated with first-line 5-fluorouracil and oxaliplatin +/- cetuximab for 17 SNPs in 10 genes involved in membrane transport (ABCC1 and ABCC2), drug biotransformation (GSTP1 and AGXT) and DNA repair (ERCC1, ERCC2, XRCC1, XRCC3, XPG and MSH6). The AGXT-rs34116584 and the ERCC2-rs238406 polymorphisms were significantly associated with progression-free survival (P=0.002 and P=0.001, respectively). Associations between 18 toxicity variables and SNPs were identified, although none were significant after Bonferroni correction for multiple comparisons. The study identified SNPs of potential use as markers of clinical outcome in oxaliplatin-treated mCRC patients. If validated in other studies, they could improve the selection of therapy in mCRC. PMID- 26261063 TI - Design of tri-level excitation signals for broadband bioimpedance spectroscopy. AB - Bioimpedance spectroscopy (BIS) measurement methods have been evolving from the traditional frequency-sweep approach to the multi-frequency simultaneous measurement technique which can drastically reduce measuring time and will be increasingly attractive for time-varying biological applications. Multi-frequency mixed (MFM) signals with sparsely distributed spectra are desirable for broadband BIS measurement. This paper proposes a synthesis method to design a series of tri level MFM signals which contain only three values (+1, 0, -1), and has majority energy distributed on its (2(n))th primary harmonics. Tri-level MFM signals have both high energy efficiency and a low crest factor. An impedance measurement experiment excited by an 8th-order tri-level MFM signal on a RC three-element equivalent model has been performed, and the results on 8 primary harmonic frequencies ranging from 8 to 1024 kHz show a high accuracy with the mean amplitude relative error of 0.41% and mean phase absolute error of 0.18 degrees , which has validated the feasibility of the tri-level MFM signals for broadband BIS measurement. PMID- 26261062 TI - Attitudes of clinicians following large-scale pharmacogenomics implementation. AB - Clinician attitudes toward multiplexed genomic testing may be vital to the success of translational programs. We surveyed clinicians at an academic medical center about their views on a large pharmacogenomics implementation, the PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) program. Participants were asked about test ordering, major factors influencing use of results, expectations of efficacy and responsibility for applying results to patient care. Virtually all respondents (99%) agreed that pharmacogenomics variants influence patients' response to drug therapy. The majority (92%) favored immediate, active notification when a clinically significant drug-genome interaction was present. However, clinicians were divided on which providers were responsible for acting on a result when a prescription change was indicated and whether patients should be directly notified of a significant result. We concluded genotype results were valued for tailoring prescriptions, but clinicians do not agree on how to appropriately assign clinical responsibility for actionable results from a multiplexed panel.The Pharmacogenomics Journal advance online publication, 11 August 2015; doi:10.1038/tpj.2015.57. PMID- 26261064 TI - Structured Frameworks to Increase the Transparency of the Assessment of Benefits and Risks of Medicines: Current Status and Possible Future Directions. AB - Structured frameworks for benefit-risk analysis in drug licensing decisions are being implemented across a number of regulatory agencies worldwide. The aim of these frameworks is to aid the analysis and communication of the benefit-risk assessment throughout the development, evaluation, and supervision of medicines. In this review, authors from regulatory agencies, pharmaceutical companies, and academia share their views on the different frameworks and discuss future directions. PMID- 26261065 TI - Effects of exposure to artificial long days on milk yield, maternal insulin-like growth factor 1 levels and kid growth rate in subtropical goats. AB - This study was designed to determine whether any relationship exists between exposure to artificial long days, milk yield, maternal plasma insulin-like growth factor 1 (IGF-1) levels, and kid growth rate in goats. One group of lactating goats was maintained under naturally decreasing day length (control group; n = 19), while in another one, they were kept under artificial long days (LD group; n = 19). Milk yield was higher in goats from the LD group than that in the control group (P < 0.05). Maternal IGF-1 levels at day 57 of lactation were higher (P < 0.05) in goats from the LD group than the levels in the control group and were positively correlated with the total milk yields per goat at days 43 and 57 of lactation (r = 0.77 and r = 0.84, respectively; P < 0.01). Daily weight gain at week 4 was higher (P < 0.01) in kids from the LD group than that in kids from the control group and was correlated with total and average IGF-1 maternal levels (r = 0.60 and r = 0.60, P < 0.05). It was concluded that submitting lactating goats to artificial long days increases milk yield, plasma IGF-1 maternal levels and the growth rate of the kids. PMID- 26261066 TI - The Use of Entheseal Changes in the Femur and Os Coxa for Age Assessment. AB - This study examined the relationship between age and entheseal modifications in the femur and os coxa for estimating age at death. Five areas on the os coxa and four on the femur were scored in 200 white individuals over 40 years of age. Statistical analyses assessed the relationship between age and entheseal modification using both raw scores and scores adjusted for body size, for each sex, and for sexes combined. Results indicate that significant relationships exist between age and entheseal modification at three sites on the femur and four on the os coxae, but the relationships are not strong enough to generate age predictions. Conversely, the most severe entheseal modifications show promise as an indicator of age in older adults. Although further research is needed using larger samples for robust statistical analyses, current data indicate these modifications can suggest an age >60, or in some cases 70, years. PMID- 26261068 TI - Influenza and pneumococcal vaccination: do older people know if they have been vaccinated? AB - OBJECTIVE: To estimate influenza and pneumococcal immunisation rates by self report and validate this with immunisation providers. METHOD: A random population telephone survey. This was followed by contacting immunisation providers of those reporting having an influenza vaccination (2009 or 2010 only) and/or pneumococcal vaccination to confirm vaccination or not. RESULTS: A total of 680 people aged 65 and older responded to the telephone survey. Seventy-five per cent of respondents self-reported influenza vaccination in 2010 and 26% self-reported having ever had the pneumococcal vaccination. Following up with immunisation providers, we found recall for influenza vaccination was confirmed in 96% of cases. For the pneumococcal vaccination, recall for vaccination was confirmed in 87% of cases. People saying they were not vaccinated for pneumococcal were subsequently confirmed as vaccinated in 77% of cases. CONCLUSIONS: In this study, self reported influenza vaccination was reliable. The term 'pneumococcal vaccination or Pneumovax' was poorly recognised by our telephone survey respondents as evident by the low rate of self-reported pneumococcal vaccination compared to a much higher rate of pneumococcal vaccinations recorded by GPs. IMPLICATIONS: While pneumococcal vaccination is an accurate term, researchers should be aware of the terminology used in general practice and the community when designing their survey. PMID- 26261067 TI - Activation of CYCD7;1 in the central cell and early endosperm overcomes cell cycle arrest in the Arabidopsis female gametophyte, and promotes early endosperm and embryo development. AB - In angiosperms, double fertilization of the egg and central cell of the megagametophyte leads to the development of the embryo and endosperm, respectively. Control of cell cycle progression in the megagametophyte is essential for successful fertilization and development. Central cell-targeted expression of the D-type cyclin CYCD7;1 (end CYCD7;1) using the imprinted FWA promoter overcomes cycle arrest of the central cell in the Arabidopsis female gametophyte in the unfertilized ovule, leading to multinucleate central cells at high frequency. Unlike FERTILIZATION-INDEPENDENT SEED (fis) mutants, but similar to lethal RETINOBLASTOMA-RELATED (rbr) mutants, no seed coat development is triggered. Unlike the case with loss of rbr, post-fertilization end CYCD7;1 in the endosperm enhances the number of nuclei during syncytial endosperm development and induces the partial abortion of developing seeds, associated with the enhanced size of the surviving seeds. The frequency of lethality was less than the frequency of multinucleate central cells, indicating that these aspects are not causally linked. These larger seeds contain larger embryos composed of more cells of wild-type size, surrounded by a seed coat composed of more cells. Seedlings arising from these larger seeds displayed faster seedling establishment and early growth. Similarly, two different embryo-lethal mutants also conferred enlarged seed size in surviving siblings, consistent with seed size increase being a general response to sibling lethality, although the cellular mechanisms were found to be distinct. Our data suggest that tight control of CYCD activity in the central cell and in the developing endosperm is required for optimal seed formation. PMID- 26261069 TI - A Simple Alternative Treatment for Syndactyly of the Toe. AB - Toe syndactyly is a common congenital malformation affecting approximately 1 in 2000 people and can cause significant emotional and psychological distress for the patient. We report a case of a 41-year-old female who was concerned about the aesthetic appearance of her bilateral second and third toe with incomplete, simple syndactyly and had requested surgical correction. A number of operative techniques have been described in the orthopedic and plastic surgery data, with no one technique proving superior. We used medical tattooing to create the appearance of a complete interdigital cleft. This low-risk, and low-cost procedure resulted in a satisfactory outcome for the patient. To the best of our knowledge, this is the first reported case using this technique, which we propose as a simple alternative to surgical correction of toe syndactyly. PMID- 26261070 TI - The kinetic fragility of liquids as manifestation of the elastic softening. AB - We show that the fragility m , the steepness of the viscosity and relaxation time close to the vitrification, increases with the degree of elastic softening, i.e. the decrease of the elastic modulus with increasing temperature, in a universal way. This provides a novel connection between the thermodynamics, via the modulus, and the kinetics. The finding is evidenced by numerical simulations and comparison with the experimental data of glassformers with widely different fragilities (33 <= m <= 115), leading to a fragility-independent elastic master curve extending over eighteen decades in viscosity and relaxation time. The master curve is accounted for by a cavity model pointing out the roles of both the available free volume and the cage softness. A major implication of our findings is that ultraslow relaxations, hardly characterised experimentally, become predictable by linear elasticity. As an example, the viscosity of supercooled silica is derived over about fifteen decades with no adjustable parameters. PMID- 26261071 TI - High-order power series expansion of the elastic interaction between conical membrane inclusions. AB - We revisit the problem of the long-range interaction between two conical proteins inserted into a lipid membrane and interacting via the induced deformation of the membrane, first considered by Goulian et al. (M. Goulian, R. Bruinsma, P. Pincus, Europhys. Lett. 22, 145 (1993); Europhys. Lett. 23, 155 (1993)). By means of a complex variables formulation and an iterative solution, we determine analytically an arbitrary high-order expansion of the interaction energy in powers of the inverse distance between two inclusions of different sizes. At leading order and for inclusions of equal sizes, we recover the result obtained by Goulian et al.. We generalize the development to inclusions of different sizes and give explicit formulas that increase the precision by ten orders in the inverse distance. PMID- 26261072 TI - Oncogenic microRNA-155 and its target PU.1: an integrative gene expression study in six of the most prevalent lymphomas. AB - The transcription factor PU.1 and its inhibitory microRNA-155 (miR-155) are important regulators of B-cell differentiation. PU.1 downregulation coupled with oncogenic miR-155 upregulation has been reported in lymphoid malignancies; however, these data have not been studied across different subtypes in relation to clinical outcomes. We studied expression of miR-155 and PU.1 in the six most prevalent human B-cell lymphomas (n = 131) including aggressive (DLBCL, HL, MCL) and indolent (B-CLL/SLL, MZL, FL) types. Levels of miR-155 and PU.1 inversely correlated in DLBCL, B-CLL/SLL, and FL tumor tissues. In HL tissues, an exceptionally high level of miR-155 was found in patients with unfavorable responses to first-line therapy and those who had shorter survival times. PU.1 downregulation was noted in B-CLL/SLL samples positive for the adverse prognostic markers CD38 and ZAP-70. Upregulation of miR-155 and downregulation of PU.1 expression are integral aspects of lymphoma biology that could mark aggressive behavior of some, but not all, lymphoma types. PMID- 26261073 TI - Characterization of unexpected postural changes during robot-assisted gait training in paraplegic patients. AB - STUDY DESIGN: This is a retrospective study. OBJECTIVES: The objectives of this study were to categorize unexpected postural changes (UPCs) during gait training in paraplegic patients with wearable gait-assist robots, to reveal the incidence of the UPC and its time-dependent changes during initial gait training period and to investigate neurological level-specific differences. SETTING: This study was conducted in Fujita Health University, Aichi, Japan. METHODS: We investigated five patients (46.2+/-14.6 years; lesion level: T6:3, T12:2). All patients had previously achieved gait with wearable robot and walker at supervision level. The UPCs were counted for 2 years and classified according to their type. The time course data were calculated from the incidence of UPCs for 10 days from initial gait training with the walker. The neurological level-specific differences were investigated between T6 and T12 injuries. RESULTS: Eighty-five UPCs were observed and classified into three categories: anterior breakdown, posterior breakdown (PBD) and mal-timing. The average rate over the entire period was 0.96+/-0.62 (incidents/h/subject). PBD, which was defined as hyperflexion of both hip joints, occurred with the highest frequency (0.64+/-0.64 incidents/h/subject). During initial gait training, there was a gradual decrease in the occurrence of UPC. For neurological level-specific differences, UPCs were observed more frequently in T6 injuries (1.36+/-0.35 incidents/h/subject) compared with T12 injuries (0.36+/ 0.31 incidents/h/subject). CONCLUSION: PBDs might be the result of near collisions between the trunk of the user and the walker, which make it difficult for the users to move their trunk over an anterior stance limb. Training that is focused upon well-timed forward movements of the walker might be required to avoid the occurrence of this common UPC. PMID- 26261074 TI - Combined detrusor-trigone BTX-A injections for urinary incontinence secondary to neurogenic detrusor overactivity. AB - OBJECTIVES: The objective of this study was to evaluate the effect and safety of trigonal injection of botulinum toxin A (BTX-A) for patients with neurological detrusor overactivity (NDO) with incontinence. METHODS: A prospective, multicenter, single-blind and randomized controlled trial was conducted between June 2011 and June 2014. Spinal cord injury patients with urinary incontinence secondary to NDO overactivity were recruited. At a 1:1 ratio, patients randomly received 200 U BTX-A intradetrusor injections excluding the trigone (the control group) or 160 U intradetrusor and 40 U intratrigonal injections (the experimental group). Patients were evaluated at baseline and at 4 and 12 weeks after injection. The efficacy and safety outcomes included Incontinence-Specific Quality-of-Life Instrument (I-QoL), voiding volume, urinary incontinence episodes, complete dryness, maximum detrusor pressure (P(detmax)) and volume at first involuntary detrusor contraction (V(FIDC)). Vesicoureteral reflux (VUR) and other adverse events were recorded. RESULTS: Ninety-six patients were recruited and 91 of them completed the trial. Among the 91 patients, 47 were randomized to the experimental group and 44 to the control group. There were no significant differences in baseline evaluation items (gender, age, duration of spinal cord injury, level of neurological injury, AIS (the American Social Injury Association) scores) between the two groups. At 12 weeks, the improvement was significantly better in the experimental group compared with that in the control group for I-QoL (26.01 vs 18.75, P=0.01), mean urinary incontinence episodes ( 5.22 vs -4.68 per day, P=0.01), complete dryness (13 vs 5, P=0.03), mean voiding volume (159.72 vs 139.07 ml, P=0.02), P(detmax) (-33.34 vs -28.02 cmH(2)O, P=0.04) and VFIDC (106.81 vs 97.86 ml, P=0.02), duration of first detrusor contraction (-41.54 vs -18.65 s, P=0.03) and the number of patients with detrusor contraction (-20 vs -9, P=0.02). In both the groups, no patients developed VUR. CONCLUSIONS: BTX-A intradetrusor and intratrigonal injections are more effective compared with those excluding the trigone for patients with NDO with incontinence. Intratrigonal injections do not induce VUR. PMID- 26261075 TI - Concerns about falling in wheelchair users with spinal cord injury--validation of the Swedish version of the spinal cord injury falls concern scale. AB - OBJECTIVE: Translation of the Spinal Cord Injury Falls Concern Scale (SCI-FCS); validation and investigation of psychometric properties. DESIGN: Translation, adaptation and validation study. SUBJECTS/PATIENTS: Eighty-seven wheelchair users with chronic SCI attending follow-up at Rehab Station Stockholm/Spinalis, Sweden. METHODS: The SCI-FCS was translated to Swedish and culturally adapted according to guidelines. Construct validity was examined with the Mann-Whitney U-test, and psychometric properties with factor and Rasch analysis. RESULTS: Participants generally reported low levels of concerns about falling. Participants with higher SCI-FCS scores also reported fear of falling, had been injured for a shorter time, reported symptoms of depression, anxiety and fatigue, and were unable to get up from the ground independently. Falls with or without injury the previous year, age, level of injury, sex and sitting balance did not differentiate the level of SCI-FCS score. The median SCI-FCS score was 21 (range 16-64). Cronbachs alpha (0.95), factor and Rasch analysis showed similar results of the Swedish as of the original version. CONCLUSION: The Swedish SCI-FCS showed high internal consistency and similar measurement properties and structure as the original version. It showed discriminant ability for fear of falling, time since injury, symptoms of depression or anxiety, fatigue and ability to get up from the ground but not for age, gender or falls. Persons with shorter time since injury, psychological concerns, fatigue and decreased mobility were more concerned about falling. In a clinical setting, the SCI-FCS might help identifying issues to address to reduce the concerns about falling. PMID- 26261076 TI - Role of inflammation in the process of clinical Kashin-Beck disease: latest findings and interpretations. AB - Kashin-Beck disease (KBD), a particular type of osteoarthritis (OA), and an endemic disease with articular cartilage damage and chondrocytes apoptosis, can affect many joints, and the most commonly affected joints are the knee, ankle, and hand. KBD has traditionally been classified as a non-inflammatory OA. However, recent studies have shown that inflammation has played an important role in the development of KBD. Nowadays, clinical KBD is not only an endemic disease, but also a combined result of many other non-endemic factors, which contains age, altered biomechanics, joint trauma and secondary OA. The characteristics of the developmental joint failure of advanced KBD, because of the biochemical and mechanical processes, are tightly linked with the interaction of joint damage and its immune response, as well as the subsequent state of chronic inflammation leading to KBD progression. In this review, we focus on the epidemiology, pathology, imaging, cytokines and transduction pathways investigating the association of inflammation with KBD; meanwhile, a wide range of data will be discussed to elicit our current hypotheses considering the role of inflammation and immune activation in KBD development. PMID- 26261077 TI - The impact of donor characteristics on the immune cell composition of mixture allografts of granulocyte-colony-stimulating factor-mobilized marrow harvests and peripheral blood harvests. AB - BACKGROUND: The association of donor characteristics with immune cell composition in allografts remains poorly understood. In this retrospective study, the effects of donor characteristics on immune cell composition in allografts were investigated. STUDY DESIGN AND METHODS: The correlations of donor characteristics with the immune cell composition in mixture allografts of granulocyte-colony stimulating factor-mobilized marrow harvests and peripheral blood harvests of 390 healthy donors (male, 240; female, 150; median age, 40 years old) were analyzed. RESULTS: The median doses of CD3+ T cells, CD4+ T cells, CD8+ T cells, CD3+CD4 CD8- T cells, and monocytes in mixture allografts were 160.57 * 10(6), 89.29 * 10(6), 56.16 * 10(6), 10.87 * 10(6), and 137.94 * 10(6)/kg, respectively. Multivariate analysis showed that younger donor age was associated with a higher dose of CD3+ T cells (p = 0.006), CD3+CD8+ T cells (p < 0.001), CD3+CD4-CD8- T cells (p = 0.004), and monocytes (p = 0.014), as well as a higher ratio of CD3+CD4-CD8- T cells/CD3+ T cells (p < 0.001) in the mixture allografts. A negative association of donor weight with CD3+ T cells (p < 0.001), CD4+ T cells (p = 0.002), CD8+ T cells (p < 0.001), and CD3+CD4-CD8- T cells (p = 0.044) was observed. The count of peripheral blood lymphocyte pre-peripheral blood apheresis was correlated with the yield of CD3+ T cells (p < 0.001) and CD4+ T cells (p = 0.001). The peripheral blood monocyte count before marrow harvest predicted the monocyte dose (p = 0.002). CONCLUSION: The results suggested that older and overweight donors should not be chosen. The monocyte and lymphocyte counts before harvest could predict the yield of immune cells in allografts. PMID- 26261078 TI - STAT3 regulated ATR via microRNA-383 to control DNA damage to affect apoptosis in A431 cells. AB - Skin cancer is a major cause of morbidity and mortality worldwide. Mounting evidence shows that exposure of the skin to solar UV radiation results in inflammation, oxidative stress, DNA damage, dysregulation of cellular signaling pathways and immunosuppression thereby resulting in skin cancer. Signal transducer and activator of transcription 3 (STAT3) is well known to function as an anti-apoptotic factor, especially in numerous malignancies, but the relationship between STAT3 activation and DNA damage response in skin cancer is still not fully understood. We now report that STAT3 inhibited DNA damage induced by UV and STAT3 mediated upregulation of GADD45gamma and MDC-1 and the phosphorylation of H2AX in UV induced DNA damage. Notably, STAT3 can increase the expression of ATR in A431 cells. Luciferase assay shows that STAT3 activates the transcription of ATR promoter. More importantly, microRNA-383 suppressed ATR expression by targeting 3' (untranslated regions)UTR of ATR in A431 cells, and STAT3 down-regulates the transcription of miR-383 promoter. Thus, these results reveal the new insight that ATR is down-regulated by STAT3-regulated microRNA-383 in A431 cells. Moreover, overexpression of STAT3 enhanced expression of antiapoptosis genes BCL-1 and MCL-1, and depletion of STAT3 sensitized A431 cells to apoptotic cell death following UV. Collectively, these studies suggest that STAT3 may be a potential target for both the prevention and treatment of human skin cancer. PMID- 26261079 TI - The yeast cell wall integrity pathway signals from recycling endosomes upon elimination of phosphatidylinositol (4,5)-bisphosphate by mammalian phosphatidylinositol 3-kinase. AB - Phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P(2)] is essential for recognition of the plasma membrane inner leaf by protein complexes. We expressed mammalian class I phosphoinositide 3-kinase (PI3K) in Saccharomyces cerevisiae to eliminate PtdIns(4,5)P(2) by its conversion into PtdIns(3,4,5)P(3), a lipid naturally missing in this yeast. This led to loss of actin function and endocytosis defects, causing a blockage in polarized secretion. Also, the cell wall integrity (CWI) mitogen-activated protein kinase (MAPK) pathway was activated, triggering a typical transcriptional response. In the absence of PtdIns(4,5)P(2) at the plasma membrane, the Pkc1 protein kinase upstream the CWI MAPK module localized to post-Golgi endosomes marked by SNARE Snc1 and Rab GTPases Ypt31 and Ypt32. Other components at the head of the pathway, like the mechanosensor Wsc1, the GTPase Rho1 and its activator the GDP/GTP exchange factor Rom2, co-localized with Pkc1 in these compartments. Chemical inhibition of PI3K proved that both CWI activation and Pkc1 relocation to endosomes are reversible. These results suggest that the CWI pathway is able to respond to loss of plasma membrane identity from recycling endosomes. PMID- 26261080 TI - Influence of tidal cycles on the endocrine control of reproductive activity in common snook (Centropomus undecimalis). AB - The aim of our study was to confirm the role of tidal pattern on the coordination of oocyte maturation and spawning in common snook Centropomus undecimalis. To do so, we studied oocyte maturation during the spawning season in relation to the tidal pattern in both males and females by means of histology and hormonal profiling along the pituitary-gonadal axis. Plasma LH levels, as well as transcript levels of gonadotropin genes (fshbeta and lhbeta) from the pituitaries of sexually mature male and female common snook were analyzed using a heterologous ELISA and quantitative RT-PCR, respectively. The fshbeta and lhbeta cDNAs were isolated and phylogenetic analysis of the deduced amino acid sequences revealed strong identity with other teleosts (75-90%). A strong link was found between tide and follicular development irrespective of the time of the day: female snook sampled on the rising tide were all found to have oocytes in the Secondary Growth Stage whereas females sampled at high tide or on the falling tide had oocytes in the later stages of maturation and ovulation. In addition, LH plasma and mRNA levels of fshbeta and lhbeta increased during the later stages of vitellogenesis peaking at ovulation in females. Plasma estradiol and testosterone significantly increased in late vitellogenesis (Secondary Growth Stage) and oocyte maturation (Eccentric Germinal Vesicle Step) respectively. Among male common snook sampled, no correlation was identified between tide and gonadal development. In addition, lhbeta mRNA expression in males peaked at the mid germinal epithelium stage as for testosterone and 11-KT in the blood while fshbeta expression and plasma LH levels peaked at late germinal epithelium stage. This study confirms the role played by tidal cycle on the entrainment of the later stages of oogenesis of common snook and provides a better understanding of the link between environmental and endocrine control of reproduction in this species. PMID- 26261081 TI - Optimization of selenizing conditions for Seleno-Lentinan and its characteristics. AB - Lentinan was successfully modified with nitric acid-sodium selenite method based on L9(3(4)) orthogonal experiments. The optimum selenizing conditions were obtained according to selenium conversion rate as follows: Lentinan of 1.0g, pH of 4.5, temperature of 70 degrees C and sodium selenite of 1.50g. The antioxidant activity assays in vitro (DPPH, reducing power, superoxide radicals and hydroxyl radicals) proved that Lentinan had stronger antioxidant activity after selenizing. The elevations of serum alanine aminotransferase and aspartate aminotransferase, as well as the abnormal hepatic architecture, verified that oral administration of Seleno-Lentinan (SL2-1) markedly alleviated oxidative damage in the liver of mice induced by D-gal. In addition, SL2-1 significantly increased total antioxidant capacity, activities and protein expressions of catalase and glutathione peroxidase and lowered malondialdehyde levels in serum and liver. Fourier transform infrared spectroscopy analysis indicated that selenium of SL2-1 was mostly existed as the formations of OSeO, SeO and SeOC. Scanning electron microscope coupled with energy dispersive X-ray spectroscopy analysis revealed that the surface structure and elemental components of Lentinan significantly changed after selenizing. The results are instructive for the development of organic selenium-supplement resource. PMID- 26261082 TI - Biochemical characterization of a detergent-stable serine alkaline protease from Caldicoprobacter guelmensis. AB - Caldicoprobacter guelmensis isolated from the hydrothermal hot spring of Guelma (Algeria) produced high amounts of extracellular thermostable serine alkaline protease (called SAPCG) (23,000U/mL). The latter was purified by ammonium sulphate precipitation, UNO Q-6 FPLC and Zorbex PSM 300 HPLC, and submitted to biochemical characterization assays. Matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF/MS) analysis revealed that the purified enzyme was a monomer, with a molecular mass of 55,824.19Da. The 19 N terminal residue sequence of SAPCG showed high homology with those of microbial proteases. The enzyme was completely inhibited by phenylmethanesulfonyl fluoride (PMSF) and diiodopropyl fluorophosphates (DFP), which suggested its belonging to the serine protease family. It showed optimum protease activity at pH 10 and 70 degrees C with casein as a substrate. The thermoactivity and thermostability of SAPCG were enhanced in the presence of 2mM Ca(2+). Its half-life times at 80 and 90 degrees C were 180 and 60min, respectively. Interestingly, the SAPCG protease exhibited significant compatibility with iSiS and Persil, and wash performance analysis revealed that it could remove blood-stains effectively. Overall, SAPCG displayed a number of attractive properties that make it a promising candidate for future applications as an additive in detergent formulations. PMID- 26261083 TI - Expression pattern of aquaporins in patients with primary nephrotic syndrome with edema. AB - The association between the expression of aquaporins (AQPs) in kidney tissues and the occurrence of edema in nephrotic syndrome (NS) remains unclear. The current study aimed to investigate this association. A total of 54 patients with primary glomerular disease, diagnosed by renal biopsy, were divided into three groups: Control, NS without edema and NS with edema. The expression of AQP1, AQP2, AQP3 and AQP4 in kidney tissues from these patients was assessed using immunohistochemistry, and urinary AQP concentrations were quantified by ELISA. Comparison of the three groups was conducted using one way analysis of variance, independent samples t-test or the Chi-square test. AQP1 was strongly expressed in the proximal tubules. The proportion of the AQP1-positive area in kidney tissues from patients with NS with edema was significantly reduced, in comparison with the other two groups. By contrast, the proportion of the AQP2-positive area in the NS with edema group was significantly higher than that of the other two groups; significant differences were also observed between the control and NS without edema groups for this parameter. Urinary AQP2 concentrations in patients with NS (with and without edema) were significantly higher than that of the control group, and exhibited a significant positive correlation with kidney tissue AQP2 concentrations. The present study demonstrated the abnormal expression pattern of AQP1-AQP4 in the kidney tissues of patients with NS, providing a basis for an improved understanding of the role of AQP in the pathogenesis of NS. PMID- 26261084 TI - Use of designer nucleases for targeted gene and genome editing in plants. AB - The ability to efficiently inactivate or replace genes in model organisms allowed a rapid expansion of our understanding of many of the genetic, biochemical, molecular and cellular mechanisms that support life. With the advent of new techniques for manipulating genes and genomes that are applicable not only to single-celled organisms, but also to more complex organisms such as animals and plants, the speed with which scientists and biotechnologists can expand fundamental knowledge and apply that knowledge to improvements in medicine, industry and agriculture is set to expand in an exponential fashion. At the heart of these advancements will be the use of gene editing tools such as zinc finger nucleases, modified meganucleases, hybrid DNA/RNA oligonucleotides, TAL effector nucleases and modified CRISPR/Cas9. Each of these tools has the ability to precisely target one specific DNA sequence within a genome and (except for DNA/RNA oligonucleotides) to create a double-stranded DNA break. DNA repair to such breaks sometimes leads to gene knockouts or gene replacement by homologous recombination if exogenously supplied homologous DNA fragments are made available. Genome rearrangements are also possible to engineer. Creation and use of such genome rearrangements, gene knockouts and gene replacements by the plant science community is gaining significant momentum. To document some of this progress and to explore the technology's longer term potential, this review highlights present and future uses of designer nucleases to greatly expedite research with model plant systems and to engineer genes and genomes in major and minor crop species for enhanced food production. PMID- 26261085 TI - Altered cGMP dynamics at the plasma membrane contribute to diarrhea in ulcerative colitis. AB - Ulcerative colitis (UC) belongs to inflammatory bowel disorders, a group of gastrointestinal disorders that can produce serious recurring diarrhea in affected patients. The mechanism for UC- and inflammatory bowel disorder associated diarrhea is not well understood. The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel plays an important role in fluid and water transport across the intestinal mucosa. CFTR channel function is regulated in a compartmentalized manner through the formation of CFTR-containing macromolecular complexes at the plasma membrane. In this study, we demonstrate the involvement of a novel macromolecular signaling pathway that causes diarrhea in UC. We found that a nitric oxide-producing enzyme, inducible nitric oxide synthase (iNOS), is overexpressed under the plasma membrane and generates compartmentalized cGMP in gut epithelia in UC. The scaffolding protein Na(+)/H(+) exchanger regulatory factor 2 (NHERF2) bridges iNOS with CFTR, forming CFTR NHERF2-iNOS macromolecular complexes that potentiate CFTR channel function via the nitric oxide-cGMP pathway under inflammatory conditions both in vitro and in vivo. Potential disruption of these complexes in Nherf2(-/-) mice may render them more resistant to CFTR-mediated secretory diarrhea than Nherf2(+/+) mice in murine colitis models. Our study provides insight into the mechanism of pathophysiologic occurrence of diarrhea in UC and suggests that targeting CFTR and CFTR-containing macromolecular complexes will ameliorate diarrheal symptoms and improve conditions associated with inflammatory bowel disorders. PMID- 26261086 TI - FIZZ1-induced myofibroblast transdifferentiation from adipocytes and its potential role in dermal fibrosis and lipoatrophy. AB - Subcutaneous lipoatrophy characteristically accompanies dermal fibrosis with de novo emergence of myofibroblasts such as in systemic sclerosis or scleroderma. Recently dermal adipocytes were shown to have the capacity to differentiate to myofibroblasts in an animal model. Transforming growth factor beta can induce this phenomenon in vitro; however its in vivo significance is unclear. Because found in inflammatory zone 1 (FIZZ1) is an inducer of myofibroblast differentiation but an inhibitor of adipocyte differentiation, we investigated its potential role in adipocyte transdifferentiation to myofibroblast in dermal fibrosis. FIZZ1 caused significant and rapid suppression of the expression of fatty acid binding protein 4 and peroxisome proliferator-activated receptor-gamma in adipocytes, consistent with dedifferentiation with loss of lipid and Oil Red O staining. The suppression was accompanied subsequently with stimulation of alpha smooth muscle actin and type I collagen expression, indicative of myofibroblast differentiation. In vivo FIZZ1 expression was significantly elevated in the murine bleomycin-induced dermal fibrosis model, which was associated with significant reduction in adipocyte marker gene expression and subcutaneous lipoatrophy. Finally, FIZZ1 knockout mice exhibited significantly reduced bleomycin-induced dermal fibrosis with greater preservation of the subcutaneous fat than wild-type mice. These findings suggested that the FIZZ1 induction of adipocyte transdifferentiation to myofibroblast might be a key pathogenic mechanism for the accumulation of myofibroblasts in dermal fibrosis. PMID- 26261087 TI - Deep transcriptome profiling of clinical Klebsiella pneumoniae isolates reveals strain and sequence type-specific adaptation. AB - Health-care-associated infections by multi-drug-resistant bacteria constitute one of the greatest challenges to modern medicine. Bacterial pathogens devise various mechanisms to withstand the activity of a wide range of antimicrobial compounds, among which the acquisition of carbapenemases is one of the most concerning. In Klebsiella pneumoniae, the dissemination of the K. pneumoniae carbapenemase is tightly connected to the global spread of certain clonal lineages. Although antibiotic resistance is a key driver for the global distribution of epidemic high-risk clones, there seem to be other adaptive traits that may explain their success. Here, we exploited the power of deep transcriptome profiling (RNA-seq) to shed light on the transcriptomic landscape of 37 clinical K. pneumoniae isolates of diverse phylogenetic origins. We identified a large set of 3346 genes which was expressed in all isolates. While the core-transcriptome profiles varied substantially between groups of different sequence types, they were more homogenous among isolates of the same sequence type. We furthermore linked the detailed information on differentially expressed genes with the clinically relevant phenotypes of biofilm formation and bacterial virulence. This allowed for the identification of a diminished expression of biofilm-specific genes within the low biofilm producing ST258 isolates as a sequence type-specific trait. PMID- 26261088 TI - MMP-9/RECK Imbalance: A Mechanism Associated with High-Grade Cervical Lesions and Genital Infection by Human Papillomavirus and Chlamydia trachomatis. AB - BACKGROUND: Matrix metalloproteinases (MMP) are important enzymes in the tumor microenvironment associated with progression of cervical intraepithelial neoplasia (CIN) toward squamous cell carcinoma (SCC) of the cervix. However, the role of MMPs in the inflammatory process associated with Chlamydia trachomatis infection concomitant with the carcinogenic process driven by HPV has not yet been addressed. In the present study, we analyzed the state of the MMP-9-RECK axis in cervical carcinogenesis. METHODS: The levels of MMP-9 and RECK expression were analyzed by immunocytochemistry in liquid-based cytology samples from 136 women with high-grade cervical lesions (CIN2/CIN3) and cervical SCC diagnosed by LLETZ, and in 196 women without cervical neoplasia or CIN1. Real-time qPCR was performed to analyze expression of MMP-9 and RECK in 15 cervical samples. The presence of HPV-DNA and other genital pathogens was evaluated by PCR. RESULTS: We found a higher expression of MMP-9 [OR, 4.2; 95% confidence interval (CI), 2.2 7.8] and lower expression of RECK (OR, 0.4; 95% CI, 0.2-0.7) in women with CIN2/CIN3/SCC when compared with women from the control group (no neoplasia/CIN1). A statistically significant association was also found between MMP-9/RECK imbalance and infection by alpha-9 HPV and C. trachomatis. The prevalence of C. trachomatis infection was significantly higher in women with high-grade cervical disease (OR, 3.7; 95% CI, 1.3-11.3). CONCLUSIONS: MMP-9/RECK imbalance in cervical smears is significantly associated with high-grade cervical diseases and infection by alpha-9 HPV and C. trachomatis. IMPACT: MMP-9/RECK imbalance during cervical inflammation induced by C. trachomatis might play a role in HPV-mediated cervical carcinogenesis. PMID- 26261089 TI - Enhanced thermal properties of novel shape-stabilized PEG composite phase change materials with radial mesoporous silica sphere for thermal energy storage. AB - Radial mesoporous silica (RMS) sphere was tailor-made for further applications in producing shape-stabilized composite phase change materials (ss-CPCMs) through a facile self-assembly process using CTAB as the main template and TEOS as SiO2 precursor. Novel ss-CPCMs composed of polyethylene glycol (PEG) and RMS were prepared through vacuum impregnating method. Various techniques were employed to characterize the structural and thermal properties of the ss-CPCMs. The DSC results indicated that the PEG/RMS ss-CPCM was a promising candidate for building thermal energy storage applications due to its large latent heat, suitable phase change temperature, good thermal reliability, as well as the excellent chemical compatibility and thermal stability. Importantly, the possible formation mechanisms of both RMS sphere and PEG/RMS composite have also been proposed. The results also indicated that the properties of the PEG/RMS ss-CPCMs are influenced by the adsorption limitation of the PEG molecule from RMS sphere with mesoporous structure and the effect of RMS, as the impurities, on the perfect crystallization of PEG. PMID- 26261091 TI - Painful exostosis of the external occipital protuberance. PMID- 26261090 TI - A glycomic approach reveals a new mycobacterial polysaccharide. AB - Mycobacterium tuberculosis lipoarabinomannan (LAM) and biosynthetically related lipoglycans and glycans play an important role in host-pathogen interactions. Therefore, the elucidation of the complete biosynthetic pathways of these important molecules is expected to afford novel therapeutic targets. The characterization of biosynthetic enzymes and transporters involved in the formation and localization of these complex macromolecules in the bacterial cell envelope largely relies on genetic manipulation of mycobacteria and subsequent analyses of lipoglycan structural alterations. However, lipoglycans are present in relatively low amounts. Their purification to homogeneity remains tedious and time-consuming. To overcome these issues and to reduce the biomass and time required for lipoglycan purification, we report here the development of a methodology to efficiently purify lipoglycans by sodium deoxycholate polyacrylamide gel electrophoresis. This faster purification method can be applied on a small amount of mycobacterial cells biomass (10-50 mg), resulting in tens of micrograms of purified lipoglycans. This amount of purified products was found to be sufficient to undertake structural analyses of lipoglycans and glycans carbohydrate domains by a combination of highly sensitive analytical procedures, involving cryoprobe NMR analysis of intact macromolecules and chemical degradations monitored by gas chromatography and capillary electrophoresis. This glycomic approach was successfully applied to the purification and structural characterization of a newly identified polysaccharide, structurally related to LAM, in the model fast-growing species Mycobacterium smegmatis. PMID- 26261092 TI - Necessity of latency period in craniofacial distraction: Investigations with in vitro microdistractor and clinical outcomes. AB - BACKGROUND: To determine the need for latency period in membranous bone distraction, we performed 1) in vitro comparison of preosteoblasts suspended in a 3D microdistraction model and 2) a clinical study comparing mandibular distraction cases with/without latency. METHODS: In the In Vitro study, Preosteoblasts polymerized in 3D-collagen gel were placed in a microdistractor and separated into three groups: 1) distraction with latency, 2) distraction without latency, and 3) static. After 2, 4, 6, and 8 days, cell proliferation, total protein levels, alkaline phosphatase activity, and osteogenic gene expression were assessed through RT-PCR. In the clinical study, patients underwent mandibular distraction in two groups: 1) latency and 2) no latency (n = 45). The rest of the distraction protocol was identical. Outcome was based on clinical examination, radiographs at six months, and 3D CT scans. RESULTS: In the In Vitro study, The distraction without latency group compared to the latency group had delays in: proliferation, total protein count, alkaline phosphatase activity, osteogenic gene expression in CBFA-1 (fourfold vs. eighteenfold), and in osteocalcin (twofold vs. sixfold). The distraction without latency group had higher apoptotic levels during the first four days compared to the latency group (68% vs. 14%). For the clinical study, similar perioperative complications (5% vs. 6%), X-ray mineralization (93% vs. 94%), bone volume, (8.6 vs. 9.1 cc) and bone density of central distraction zone (78% vs. 81%) were observed with or without latency. CONCLUSIONS: In vitro studies showed poorer results in cell survival, proliferation and osteogenic activity compared to distraction with latency; yet, clinically, there were no differences in distraction with latency versus without. PMID- 26261093 TI - The nomenclature of groin dissection for melanoma - Time to simplify. AB - INTRODUCTION: A wide variety of terms are used to describe different extents of groin dissection for stage 3 melanoma which may result in confusion and reduce effectiveness of research. We aim to evaluate the published terminology. METHODS: A PubMed review was conducted using the terms 'melanoma' plus 'inguinal'; 'groin'; 'pelvic'; 'ilioinguinal' dissection. 63 papers were included from 1956 to March 2015. A review of anatomy and coding was also conducted. RESULTS: Inguinal dissection was described using 8 terms from 56 papers with 7 papers using multiple terms for the same procedure. 'Superficial dissection' was the most common term despite inguinal-nodal tissue being separated into superficial and deep layers anatomically. ICD10PCS and OPSC code for 'inguinal' with no anatomical definition, CPT codes for 'inguinofemoral/superficial'. Combination inguino-pelvic dissection was described using 11 terms from 51 papers with 15 papers using multiple terms for the same procedure. 'Ilioinguinal' and 'Deep' were the most common despite most pelvic dissections including obturator nodes. ICD10PCS and OPSC code for 'pelvic' with no anatomical definition and CPT codes for 'superficial plus pelvic'. CONCLUSION: Many different terms are used to describe the same procedures, often within the same article. The lack of clarity can confuse readers, hinder comparative research and jeopardise patient care. Imprecise documentation of anatomical definition limits surgical outcome reporting and can impede planning for revision surgery. Standardisation is necessary and groin dissection should be defined by anatomical boundaries e.g. 'superficial' and 'deep' inguinal; 'pelvic'; 'inguino-pelvic' with clear documentation of extent. PMID- 26261094 TI - Multiplane hyaluronic acid (EME) in female Chinese rhinoplasty using blunt and sharp needle technique. AB - BACKGROUND: Hyaluronic acid has been widely used for nonsurgical rhinoplasty. Little literature focuses on Chinese women of the Han nationality, who have a characteristic flattened facial contour. Projection of the nose, including the nasal dorsum, nasal tip, and columella, plays an important role in achieving an attractive face. AIM: The aim of this study was to investigate the application of multiplane hyaluronic acid in rhinoplasty using blunt and sharp needle technique. METHOD: From June 2011 to February 2014, 280 cases of nonsurgical rhinoplasty by hyaluronic acid were applied; 1-9 months follow-up showed satisfactory appearance. RESULT: Postoperative results showed no complications, such as infection or flap necrosis. CONCLUSION: For esthetic and safety considerations, we suggest multiple plane injections using blunt combined with sharp needle filling techniques. PMID- 26261095 TI - Performance of a Culturally Tailored Cognitive-Behavioral Intervention Integrated in a Public Health Setting to Reduce Risk of Antepartum Depression: A Randomized Controlled Trial. AB - INTRODUCTION: Cognitive-behavioral group interventions have been shown to improve depressive symptoms in adult populations. This article details the feasibility and efficacy of a 6-week, culturally tailored, cognitive-behavioral intervention offered to rural, minority, low-income women at risk for antepartum depression. METHODS: A total of 146 pregnant women were stratified by high risk for antepartum depression (Edinburgh Postnatal Depression Scale [EPDS] score of 10 or higher) or by low-moderate risk (EPDS score of 4-9) and randomized to a cognitive behavioral intervention or treatment as usual. Differences in mean change of EPDS and Beck Depression Inventory (BDI)-II scores for low-moderate and high-risk women in the cognitive-behavioral intervention and treatment as usual for the full sample were assessed from baseline (T1), posttreatment (T2), and one-month follow-up (T3), and for African American women in the subsample. RESULTS: Both the cognitive-behavioral intervention and treatment-as-usual groups had significant reductions in the EPDS scores from T1 to T2 and T1 to T3. In women at high risk for depression (n = 62), there was no significant treatment effect from T1 to T2 or T3 for the EPDS. However, in low-moderate risk women, there was a significantly greater mean change in the BDI-II scores from significant decrease in the BDI-II scores from T1 to T2 (4.92 vs 0.59, P = .018) and T1 to T3 (5.67 vs 1.51, P = .04). Also, the cognitive-behavioral intervention significantly reduced EPDS scores for African American women at high risk (n = 43) from T1 to T2 (5.59 vs 2.18, P = .02) and from T1 to T3 (6.32 vs 3.14, P = .04). DISCUSSION: A cognitive-behavioral intervention integrated within prenatal clinics is feasible in this sample, although attrition rates were high. Compared to treatment as usual, the cognitive-behavioral intervention reduced depressive symptoms for African American women at high risk for antepartum depression and for the full sample of women at low-moderate risk for antepartum depression. These promising findings need to be replicated in a larger controlled clinical trial that incorporates methods to maintain greater participant engagement. PMID- 26261096 TI - Differential temporal effects of sclerostin antibody and parathyroid hormone on cancellous and cortical bone and quantitative differences in effects on the osteoblast lineage in young intact rats. AB - Sclerostin antibody (Scl-Ab) and parathyroid hormone (PTH) are bone-forming agents that have different modes of action on bone, although a study directly comparing their effects has not been conducted. The present study investigated the comparative quantitative effects of these two bone-forming agents over time on bone at the organ, tissue, and cellular level; specifically, at the level of the osteoblast (Ob) lineage in adolescent male and female rats. Briefly, eight week old male and female Sprague-Dawley rats were administered either vehicle, Scl-Ab (3 or 50mg/kg/week subcutaneously), or human PTH (1-34) (75 MUg/kg/day subcutaneously) for 4 or 26 weeks. The 50mg/kg Scl-Ab and the PTH dose were those used in the respective rat lifetime pharmacology studies. Using robust stereological methods, we compared the effects of these agents specifically at the level of the Ob lineage in vertebrae from female rats. Using RUNX2 or nestin immunostaining, location, and morphology, the total number of osteoprogenitor subpopulations, Ob, and lining cells were estimated using the fractionator or proportionator estimators. Density estimates were also calculated referent to total bone surface, total Ob surface, or total marrow volume. Scl-Ab generally effected greater increases in cancellous and cortical bone mass than PTH, correlating with higher bone formation rates (BFR) at 4 weeks in the spine and mid-femur without corresponding increases in bone resorption indices. The increases in vertebral BFR/BS at 4 weeks attenuated with continued treatment to a greater extent with Scl-Ab than with PTH. At 4 weeks, both Scl-Ab and PTH effected equivalent increases in total Ob number (Ob.N). Ob density on the formative surfaces (Ob.N/Ob.S) remained similar across groups while mineral apposition rate (MAR) was significantly higher with Scl-Ab at week 4, reflecting an increase in individual Ob vigor relative to vehicle and PTH. After 26 weeks, Scl-Ab maintained BFR/BS with fewer Ob and lower Ob.N/Ob.S by increasing the Ob footprint (bone surface area occupied by an Ob) and increasing MAR, compared with PTH. The lower Ob.N and Ob.N/Ob.S with Scl-Ab at 26 weeks were associated with decreased osteoprogenitor numbers compared with both vehicle and PTH, an effect not evident at week 4. Osteoprogenitor numbers were generally positively correlated with Ob.N across groups and timepoints, suggesting dynamic coordination between the progenitor and Ob populations. The time-dependent reductions in subpopulations of the Ob lineage with Scl-Ab may be integral to the greater attenuation or self-regulation of bone formation observed at the vertebra, as PTH required more Ob at the formative site with correlative increased numbers of progenitors compared with Scl-Ab indicating potentially greater stimulus for progenitor pool proliferation or differentiation. PMID- 26261097 TI - Automatic classification of apnea/hypopnea events through sleep/wake states and severity of SDB from a pulse oximeter. AB - This study proposes a method of automatically classifying sleep apnea/hypopnea events based on sleep states and the severity of sleep-disordered breathing (SDB) using photoplethysmogram (PPG) and oxygen saturation (SpO2) signals acquired from a pulse oximeter. The PPG was used to classify sleep state, while the severity of SDB was estimated by detecting events of SpO2 oxygen desaturation. Furthermore, we classified sleep apnea/hypopnea events by applying different categorisations according to the severity of SDB based on a support vector machine. The classification results showed sensitivity performances and positivity predictive values of 74.2% and 87.5% for apnea, 87.5% and 63.4% for hypopnea, and 92.4% and 92.8% for apnea + hypopnea, respectively. These results represent better or comparable outcomes compared to those of previous studies. In addition, our classification method reliably detected sleep apnea/hypopnea events in all patient groups without bias in particular patient groups when our algorithm was applied to a variety of patient groups. Therefore, this method has the potential to diagnose SDB more reliably and conveniently using a pulse oximeter. PMID- 26261099 TI - Does the technique employed for skin temperature assessment alter outcomes? A systematic review. AB - Skin temperature is an important physiological measure that can reflect the presence of illness and injury as well as provide insight into the localised interactions between the body and the environment. The aim of this systematic review was to analyse the agreement between conductive and infrared means of assessing skin temperature which are commonly employed in in clinical, occupational, sports medicine, public health and research settings.Full-text eligibility was determined independently by two reviewers. Studies meeting the following criteria were included in the review: (1) the literature was written in English, (2) participants were human (in vivo), (3) skin surface temperature was assessed at the same site, (4) with at least two commercially available devices employed-one conductive and one infrared-and (5) had skin temperature data reported in the study.A computerised search of four electronic databases, using a combination of 21 keywords, and citation tracking was performed in January 2015. A total of 8,602 were returned.Methodology quality was assessed by two authors independently, using the Cochrane risk of bias tool.A total of 16 articles (n = 245) met the inclusion criteria.Devices are classified to be in agreement if they met the clinically meaningful recommendations of mean differences within +/-0.5 degrees C and limits of agreement of +/-1.0 degrees C.Twelve of the included studies found mean differences greater than +/-0.5 degrees C between conductive and infrared devices. In the presence of external stimulus (e.g. exercise and/or heat) five studies found exacerbated measurement differences between conductive and infrared devices.This is the first review that has attempted to investigate presence of any systemic bias between infrared and conductive measures by collectively evaluating the current evidence base. There was also a consistently high risk of bias across the studies, in terms of sample size, random sequence generation, allocation concealment, blinding and incomplete outcome data.This systematic review questions the suitability of using infrared cameras in stable, resting, laboratory conditions. Furthermore, both infrared cameras and thermometers in the presence of sweat and environmental heat demonstrate poor agreement when compared to conductive devices. These findings have implications for clinical, occupational, public health, sports science and research fields. PMID- 26261098 TI - Fluorogenic Assay for Inhibitors of HIV-1 Protease with Sub-picomolar Affinity. AB - A fluorogenic substrate for HIV-1 protease was designed and used as the basis for a hypersensitive assay. The substrate exhibits a kcat of 7.4 s(-1), KM of 15 MUM, and an increase in fluorescence intensity of 104-fold upon cleavage, thus providing sensitivity that is unmatched in a continuous assay of HIV-1 protease. These properties enabled the enzyme concentration in an activity assay to be reduced to 25 pM, which is close to the Kd value of the protease dimer. By fitting inhibition data to Morrison's equation, Ki values of amprenavir, darunavir, and tipranavir were determined to be 135, 10, and 82 pM, respectively. This assay, which is capable of measuring Ki values as low as 0.25 pM, is well suited for characterizing the next generation of HIV-1 protease inhibitors. PMID- 26261100 TI - Low-Grade, Nonintestinal Nonsalivary Sinonasal Adenocarcinoma Associated With an Exophytic Schneiderian Papilloma: A Case Report. AB - Sinonasal adenocarcinoma is a rare tumor of the head and neck accounting for 10% to 20% of all primary malignancies of the nose and paranasal sinuses. There tumors are classified as salivary, intestinal and nonintestinal, nonsalivary. Low grade nonintestinal nonsalivary are rare tumors whose diagnosis is essentially that of exclusion. Here we present the first case of one such tumor associated with an exophyic Schneiderian papilloma. A 71-year-old retired aerospace engineer presented with a 1-year history of severe nasal obstruction. Endoscopy and compted tomography imaging demonstrated a polypoid lesion occupying his entire right nasal cavity extending into and filling the nasopharynx. Biopsy suggested adenocarcinoma, at least in situ and the patient subsequently underwent complete resection. Pathologic evaluation demonstrated polypoid tumor consistent with a low-grade papillary adenocarcinoma with micropapillary architecture associated with a small amount of residual exophytic Schneiderian papilloma. Immunohistochemistry revealed diffuse expression of CK7, CK 5/6, and S100 protein in tumor cells. Expression of p63 was seen in basal cells only. Tumor cells did not show expression of CK20, CDX2 (intestinal markers), mammaglobin, GATA3 (salivary markers), PAX8, WT1, nor estrogen, progesterone, or androgen receptors confirming its nonintestinal nonsalivary differentiation. PMID- 26261101 TI - Mucosal CD30-Positive T-Cell Lymphoproliferative Disorder Arising in the Oral Cavity Following Dental Implants: Report of the First Case. AB - Mucosal CD30-positive T-cell lymphoproliferative disorder (CD30+ T-cell LPD) is a novel entity with unique clinicopathological features and an indolent behavior. Here we report the first case of mucosal CD30+ T-cell LPD arising in the oral cavity following dental implant. A 70-year-old woman presented with swelling and redness of the oral mucosa of right maxilla and left mandible surrounding dental implants that had been placed 8 years previously. Radiological examination revealed enhancing oral lesions and multiple cervical lymph nodes. Microscopic examination showed diffuse infiltration of large anaplastic cells with characteristic morphology of hallmark cells described in anaplastic large cell lymphoma. These cells were diffusely positive for CD30, CD3, CD4, CD2, CD5, CD7, TIA-1, and TCRbetaF1, but negative for CD20, CD8, CD45, EMA, ALK, and Epstein Barr virus. T-cell monoclonality was detected in a TCRgamma gene rearrangement study. This a unique case of mucosal CD30+ T-cell LPD with unusual presentation following dental implant. PMID- 26261102 TI - Cutaneous Squamous Cell Carcinomas of the Lower Extremities Show Distinct Clinical and Pathologic Features. AB - Cutaneous squamous cell carcinomas mainly affect older, predominantly male patients. Most are due to chronic ultraviolet exposure, and associated with actinic keratoses. On the lower extremities, they occur more commonly in women. However, data on these tumors as a distinct group are scarce. We evaluated 61 squamous cell carcinomas of the lower extremities. Overall, 69% of patients were female. Mean age was 75 years. More than 90% of tumors were well differentiated, 3% showed perineural invasion, and none lymphovascular invasion. In all, 63.9% showed evidence of severe chronic sun damage. Associated actinic keratoses were identified in only 13% of cases. By contrast, 80% were associated with distinctive basal epidermal proliferations with a retiform growth pattern. These proliferations were evaluated immunohistochemically for keratinocyte stem cell markers, p53 and Notch1 in 15 cases. All cases were positive for cytokeratin 14, p53, and Notch1 (with variable intensity in the latter 2), and predominantly negative for cytokeratin 19. Interestingly, basal retiform proliferations were positive for cytokeratin 15 in 66% of cases. Fifteen head and neck squamous cell carcinomas were evaluated in comparison. Those lacked associated basal retiform proliferations except in 1 case. In contrast, 87% were associated with actinic keratoses and 100% with severe chronic sun damage. Actinic keratoses associated with head and neck tumors showed cytokeratin 15 staining only in 7% of cases (P = .003 compared with cytokeratin 15 in basal retiform proliferations associated with leg carcinomas). These findings support the hypothesis that lower extremity squamous cell carcinomas are distinct and may exhibit a pathogenesis less reliant on actinic damage. PMID- 26261104 TI - Efficacy and Biological Activity of Imatinib in Metastatic Dermatofibrosarcoma Protuberans (DFSP). AB - PURPOSE: To report on imatinib mesylate (IM) in patients with metastatic dermatofibrosarcoma protuberans (DFSP)/fibrosarcomatous (FS)-DFSP and on the impact of the treatment on tumor biology. EXPERIMENTAL DESIGN: Ten consecutive patients treated with IM from 2007 to 2015 for a metastatic relapse from DFSP/FS DFSP were identified. FISH analysis for COL1A1-PDGFB was performed. Two IM treated and 4 naive FS-DFSP were transcriptionally profiled by RNAseq on HiScanSQ platform. Differential gene expression was analyzed with edgeR (Bioconductor), followed by hierarchical clustering and Principal Component Analysis. RESULTS: All cases featured fibrosarcomatous in the metastasis and retained the COL1A1 PDGFB. Best RECIST response was: 8 partial response, 1 stable disease, and 1 progressive disease. Median progression-free survival was 11 months. Five patients received surgery after IM and all relapsed. IM was restored in 4 patients with a new response. After IM, the most upregulated genes included those encoding for immunoglobulins and those affecting functions and differentiation of endothelial cells. Pathway enrichment analysis revealed upregulation in genes involved in antigen processing and presentation, natural killer-mediated cytotoxicity, and drug and xenobiotics metabolism. Conversely, a significant down regulation of kinase signaling pathways was detected. CONCLUSIONS: All metastatic cases were fibrosarcomatous. Most patients responded to IM, but PFS was shorter than reported in published series which included both DFSP and FS-DFSP. All patients operated after IM had a relapse, suggesting that IM cannot eradicate metastatic cases and that the role of surgery is limited. Transcriptional profile of naive and posttreatment samples pointed the contribution of immune infiltrates in sustaining the response to IM. PMID- 26261103 TI - ESR1 Mutations in Circulating Plasma Tumor DNA from Metastatic Breast Cancer Patients. AB - PURPOSE: Mutations in the estrogen receptor (ER)alpha gene, ESR1, have been identified in breast cancer metastases after progression on endocrine therapies. Because of limitations of metastatic biopsies, the reported frequency of ESR1 mutations may be underestimated. Here, we show a high frequency of ESR1 mutations using circulating plasma tumor DNA (ptDNA) from patients with metastatic breast cancer. EXPERIMENTAL DESIGN: We retrospectively obtained plasma samples from eight patients with known ESR1 mutations and three patients with wild-type ESR1 identified by next-generation sequencing (NGS) of biopsied metastatic tissues. Three common ESR1 mutations were queried for using droplet digital PCR (ddPCR). In a prospective cohort, metastatic tissue and plasma were collected contemporaneously from eight ER-positive and four ER-negative patients. Tissue biopsies were sequenced by NGS, and ptDNA ESR1 mutations were analyzed by ddPCR. RESULTS: In the retrospective cohort, all corresponding mutations were detected in ptDNA, with two patients harboring additional ESR1 mutations not present in their metastatic tissues. In the prospective cohort, three ER-positive patients did not have adequate tissue for NGS, and no ESR1 mutations were identified in tissue biopsies from the other nine patients. In contrast, ddPCR detected seven ptDNA ESR1 mutations in 6 of 12 patients (50%). CONCLUSIONS: We show that ESR1 mutations can occur at a high frequency and suggest that blood can be used to identify additional mutations not found by sequencing of a single metastatic lesion. PMID- 26261105 TI - User experience with a health insurance coverage and benefit-package access: implications for policy implementation towards expansion in Nigeria. AB - BACKGROUND: Developing countries are devising strategies and mechanisms to expand coverage and benefit-package access for their citizens through national health insurance schemes (NHIS). In Nigeria, the scheme aims to provide affordable healthcare services to insured-persons and their dependants. However, inclusion of dependants is restricted to four biological children and a spouse per user. This study assesses the progress of implementation of the NHIS in Nigeria, relating to coverage and benefit-package access, and examines individual factors associated with the implementation, according to users' perspectives. METHODS: A retrospective, cross-sectional survey was done between October 2010 and March 2011 in Kaduna state and 796 users were randomly interviewed. Questions regarding coverage of immediate-family members and access to benefit-package for treatment were analysed. Indicators of coverage and benefit-package access were each further aggregated and assessed by unit-weighted composite. The additive-ordinary least square regression model was used to identify user factors that may influence coverage and benefit-package access. RESULTS: With respect to coverage, immediate-dependants were included for 62.3% of the users, and 49.6 rated this inclusion 'good' (49.6%). In contrast, 60.2% supported the abolishment of the policy restriction for non-inclusion of enrolees' additional children and spouses. With respect to benefit-package access, 82.7% of users had received full treatments, and 77.6% of them rated this as 'good'. Also, 14.4% of users had been refused treatments because they could not afford them. The coverage of immediate dependants was associated with age, sex, educational status, children and enrolment duration. The benefit-package access was associated with types of providers, marital status and duration of enrolment. CONCLUSION: This study revealed that coverage of family members was relatively poor, while benefit package access was more adequate. Non-inclusion of family members could hinder effective coverage by the scheme. Potential policy implications towards effective coverage and benefit-package access are discussed. PMID- 26261107 TI - Expected surgical competencies of an Indian medical graduate: a gap analysis using a cross-sectional survey. AB - BACKGROUND: In 2010, the Medical Council of India published the Vision 2015 document, which sought to create an 'Indian Medical Graduate' as a 'physician of first contact of the community while being globally relevant'. This vision for undergraduate medical education is proposed to be realised through a competency based curriculum. We conducted a gap analysis using a cross-sectional survey to document surgeons' perceptions regarding competencies identified in surgery. METHODS: Eight competencies specific to surgery are proposed, which formed the basis for the study. We defined sub-competencies for each of these and developed a questionnaire containing ratings of importance and ability for the sub competencies from low to very high on a 4-point Likert scale. The questionnaire was administered to 450 surgeons attending a state-level annual conference in surgery asking them to provide the importance ratings and their own ability on those (sub) competencies when they graduated. The importance and ability ratings were ranked and a gap analysis was done. RESULTS: The study response rate was 69.8%. While most competencies were perceived by the surgeons as being highly important, their self-ratings revealed a statistically significant gap between importance and ability when they graduated. They also rated themselves as being more competent on some than on others. Some competencies were high on importance as well as on ability, while others were high on importance but low on ability, revealing a gap. A low importance-high ability relationship was seen for a few competencies. Competencies related to emergency and trauma care and communication had the largest gaps. DISCUSSION: The gaps identified in surgical competencies for graduating physicians are specific and have implications for the competency based curriculum and implementation in terms of teaching, assessment and faculty development. It also has implications for seamless transition between undergraduate and postgraduate competencies, as all of these are prerequisites at the start of a surgical residency. PMID- 26261108 TI - Research in surgery and anesthesia: challenges for post-graduate trainees in Uganda. AB - BACKGROUND: Research is critical to the training and practice of surgery and anesthesia in all settings, regardless of available resources. Unfortunately, the output of surgical and perioperative research from Africa is low. Makerere University College of Health Sciences' (MakCHS) surgical and anesthesia trainees are required to conduct research, though few publish findings or go on to pursue careers that incorporate research. We believe that early career experiences with research may greatly influence physicians' future conduct and utilization of research. We therefore sought to analyze trainee experiences and perceptions of research to identify interventions that could increase production of high quality, locally led, surgical disease research in our resource-constrained setting. METHODS: Following ethical approval, a descriptive, cross-sectional survey was conducted among anesthesia and surgery trainees using a pretested, self-administered questionnaire. Data were tabulated and frequency tables generated. RESULTS: Of the 43 eligible trainees, 33 (77%) responded. Ninety-four percent identify research as important to career development, and 85% intend to publish their dissertations. The research dissertation is considered a financial burden by 64%. Also, 49% reported that their departments place low value on their research, and few of the findings are utilized. Trainees report that lack of protected research time, difficulty in finding research topics, and inadequate mentorship are the main challenges to conducting research projects. DISCUSSION: Our anesthesia and surgery trainees spend considerable resources on research endeavors. Most have significant interest in incorporating research into their careers, and most intend to publish their work in peer-reviewed journals. Here we identify several challenges facing trainees including research project development, financing and mentorship. We hope to use these results to improve support in these areas for our trainees and those in other resource-limited areas. PMID- 26261109 TI - Small group learning: effect on item analysis and accuracy of self-assessment of medical students. AB - BACKGROUND: Small group sessions are regarded as a more active and student centered approach to learning. Item analysis provides objective evidence of whether such sessions improve comprehension and make the topic easier for students, in addition to assessing the relative benefit of the sessions to good versus poor performers. Self-assessment makes students aware of their deficiencies. Small group sessions can also help students develop the ability to self-assess. This study was carried out to assess the effect of small group sessions on item analysis and students' self-assessment. METHODS: A total of 21 female and 29 male first year medical students participated in a small group session on topics covered by didactic lectures two weeks earlier. It was preceded and followed by two multiple choice question (MCQ) tests, in which students were asked to self-assess their likely score. The MCQs used were item analyzed in a previous group and were chosen of matching difficulty and discriminatory indices for the pre- and post-tests. RESULTS: The small group session improved the marks of both genders equally, but female performance was better. The session made the items easier; increasing the difficulty index significantly but there was no significant alteration in the discriminatory index. There was overestimation in the self-assessment of both genders, but male overestimation was greater. The session improved the self-assessment of students in terms of expected marks and expectation of passing. DISCUSSION: Small group session improved the ability of students to self-assess their knowledge and increased the difficulty index of items reflecting students' better performance. PMID- 26261110 TI - The operating theatre as classroom: a qualitative study of learning and teaching surgical competencies. AB - BACKGROUND: There has been a worldwide movement toward competency-based medical education and training. However, this is the first qualitative study to analyze the perceptions of surgical trainees and surgeons toward competency-based education in the operating theatre. We aim to examine views toward the specific learning and teaching of the nine competencies of the Royal Australasian College of Surgeons (RACS) and to explore perceived ideal conditions and challenges for learning and teaching these competencies in the operating theatre. METHODS: Individual semi-structured interviews with surgical trainees and surgeons in the specialty of General Surgery. Ten surgical trainees and surgeons who worked together were purposively sampled, for maximum variation, from an outer metropolitan public hospital in Melbourne, Australia, to identify emergent themes relating to learning and teaching surgical competencies in the operating theatre. RESULTS: Five themes were identified as: (1) Learning and teaching specific surgical competencies is through relationship based mentoring and experiential learning; (2) Ideal conditions and challenges in the operating theatre are availability of time and personal attitude; (3) Level of pre-operative briefing was variable; (4) Intra-operative teaching is perceived as structured; and, (5) Post-operative debriefing is recognized as ideal but not consistently performed. DISCUSSION: Professional relationships are important to both surgical trainees and surgeons in the process of learning and teaching competencies. Ad hoc apprenticeship style learning is perceived to remain prominent in the operating theatre. Sufficient time for training is valued by both groups. The surgical competencies are inherently different to each other. Some appear more difficult to learn and teach in the operating theatre, with technical expertise most readily identified and health advocacy least so. Elements of guided discovery learning and other educational models are described. Further emphasis on structured competency-based teaching methods may be beneficial for surgical trainees, surgeons and other specialties, both in Australia and worldwide. PMID- 26261111 TI - Comparison of resident performance in interpreting mammography results using a probabilistic or a natural frequency presentation: a multi-institutional randomized experimental study. AB - BACKGROUND: Residents are being increasingly challenged on how best to integrate diagnostic information in making decisions about patient care. The aim of this study is to assess the ability of residents to accurately integrate statistical data from a screening mammography test in order to estimate breast cancer probability and to investigate whether a simple alteration of the representation mode of probabilities into natural frequencies facilitates these computations. METHODS: A multi-institutional randomized controlled study of residents was performed in eight major hospitals in the city of Athens. Residents were asked to estimate the positive predictive value of the screening mammography test given its sensitivity and 1-specificity as well as the prevalence of breast cancer in the relevant population. One version of the scenario was presented in the single event probability format that is commonly used in the medical literature, while the other used the natural frequency representation. The two questionnaire versions were randomly assigned to the participants. RESULTS: Out of 200 residents, 153 completed and returned the questionnaire (response rate 76.5%). Although more than one-third of the residents reported excellent or close to excellent familiarity with sensitivity and positive predictive value, the majority of responses (79.1%) were incorrect. However, a significantly higher proportion of residents in the natural frequency group (n = 88) selected the correct response compared with residents (n = 65) in the single-event probability group (28.4% vs 10.8%; 95% confidence intervals of the difference between the two proportions = 5.6-29.7%; P < 0.01). DISCUSSION: Residents more often correctly understand test performance accuracy when test characteristics are presented to them as natural frequency representations than the more common approach of presenting single event probabilities. Educators and journal editors should be aware of this facilitative effect. PMID- 26261112 TI - Translation and validation of patient-practitioner orientation scale in Sri Lanka. AB - BACKGROUND: Practice of family medicine and patient centeredness does not get the deserved attention in clinical practice and teaching in Sri Lanka. Non availability of tools for assessment of patient centeredness deters the process of curricular development and research. The Patient-Practitioner Orientation Scale (PPOS) is a self-administered tool that assesses patient-centeredness in both health care professionals and patients. This study has translated and validated the PPOS to Sinhala language. METHODS: Translation and cross-cultural adaptation were carried out using forward and backward translation method. The psychometric properties of a pretested new Sinhala version of PPOS (PPOS-Sinhala) was tested in a convenience sample of 1367 patients and health professionals. Temporal stability was tested in a sub-sample of 140 individuals. The comparability of the PPOS scores and association with sex and level of education with those reported for Western populations were examined to establish construct validity. RESULTS: The sample included 543 medical students, 67 doctors, 335 allied health students and 422 patients. Cronbach's alpha for these groups ranged from 0.48 to 0.53 for sharing, 0.42 to 0.53 for caring, and 0.62 to 0.65 for total score. Intraclass correlation coefficients of 0.56, 0.6, and 0.4 were observed for the Total, Sharing, and Caring sub-scales, respectively. PPOS scores did not vary significantly for men and women. Health professionals exhibited higher scores than patients. Age was negatively associated and education level was positively associated with PPOS. DISCUSSION: PPOS-Sinhala is stable, sufficiently valid and reliable to evaluate patient centeredness among Sinhala speaking health care professionals and patients. Lower internal consistency is found for a few items in the instrument which requires further development. PPOS scores and their correlates for this Sri Lankan population were more similar to that found in other populations in this region than for scores and correlates found in the US. PMID- 26261113 TI - Effectiveness of team-based learning in microbiology: a non-randomized control study. AB - BACKGROUND: As per the present curriculum in India, pre- and paraclinical subjects are taught away from the clinical setting. Therefore, students fail to connect the subject taught through didactic lectures to the clinical setting. Team-based learning (TBL) can be used in conjunction with lectures to teach applied microbiology. This study aims to evaluate the effectiveness of TBL sessions in conjunction with lectures to enhance learning of applied microbiology, among Indian students. METHODS: All students enrolled in the study were taught systemic bacteriology through lectures. Of the 88 students, 49 students (study group) attended TBL sessions on the topics of diarrhea, fever of unknown origin, urinary tract infection and 39 students (control group) preferred self-study on the topics without attending the TBL sessions. Students' feedback on their perception on TBL sessions was collected using a questionnaire of 10 items. The performance of both the groups on the pre- and post-test were analyzed using unpaired t-test and analysis of variance (ANOVA). Gender-wise performance within the teams was analyzed by paired t-test using SPSS version 12. RESULTS: The TBL group outperformed the self-study group on the post-test [F 1 = 5.521, P = 0.021]. Female students as a whole performed better than males on the pre-test, scoring higher within both the TBL and self-study groups. Male students in the TBL group performed significantly better on the post-test than female students who participated in TBL sessions (P = 0.013). Students generally enjoyed and appreciated the TBL sessions. DISCUSSION: TBL sessions can be used judiciously in combination with the lectures to enhance learning of applied microbiology in India. In this study, TBL improved the performance of male students over self study, but performance for female students following TBL was no better than when they simply studied by themselves. PMID- 26261114 TI - Development of active learning modules in pharmacology for small group teaching. AB - BACKGROUND: Current teaching in pharmacology in undergraduate medical curriculum in India is primarily drug centered and stresses imparting factual knowledge rather than on pharmacotherapeutic skills. These skills would be better developed through active learning by the students. Hence modules that will encourage active learning were developed and compared with traditional methods within the Seth GS Medical College, Mumbai. METHODS: After Institutional Review Board approval, 90 second year undergraduate medical students who consented were randomized into six sub-groups, each with 15 students. Pre-test was administered. The three sub groups were taught a topic using active learning modules (active learning groups), which included problems on case scenarios, critical appraisal of prescriptions and drug identification. The remaining three sub-groups were taught the same topic in a conventional tutorial mode (tutorial learning groups). There was crossover for the second topic. Performance was assessed using post-test. Questionnaires with Likert-scaled items were used to assess feedback on teaching technique, student interaction and group dynamics. RESULTS: The active and tutorial learning groups differed significantly in their post-test scores (11.3 +/- 1.9 and 15.9 +/- 2.7, respectively, P < 0.05). In students' feedback, 69/90 students had perceived the active learning session as interactive (vs. 37/90 students in tutorial group) and enhanced their understanding vs. 56/90 in tutorial group), aroused intellectual curiosity (47/90 students of active learning group vs. 30/90 in tutorial group) and provoked self-learning (41/90 active learning group vs. 14/90 in tutorial group). Sixty-four students in the active learning group felt that questioning each other helped in understanding the topic, which was the experience of 25/90 students in tutorial group. Nevertheless, students (55/90) preferred tutorial mode of learning to help them score better in their examinations. DISCUSSION: In this study, students preferred an active learning environment, though to pass examinations, they preferred the tutorial mode of teaching. Further efforts are required to explore the effects on learning of introducing similar modules for other topics. PMID- 26261115 TI - Challenges of interprofessional team training: a qualitative analysis of residents' perceptions. AB - BACKGROUND: Simulation-based interprofessional team training is thought to improve patient care. Participating teams often consist of both experienced providers and trainees, which likely impacts team dynamics, particularly when a resident leads the team. Although similar team composition is found in real-life, debriefing after simulations puts a spotlight on team interactions and in particular on residents in the role of team leader. The goal of the current study was to explore residents' perceptions of simulation-based interprofessional team training. METHODS: This was a secondary analysis of a study of residents in the pediatric residency training program at the University of California, San Francisco (United States) leading interprofessional teams in simulated resuscitations, followed by facilitated debriefing. Residents participated in individual, semi-structured, audio-recorded interviews within one month of the simulation. The original study aimed to examine residents' self-assessment of leadership skills, and during analysis we encountered numerous comments regarding the interprofessional nature of the simulation training. We therefore performed a secondary analysis of the interview transcripts. We followed an iterative process to create a coding scheme, and used interprofessional learning and practice as sensitizing concepts to extract relevant themes. RESULTS: 16 residents participated in the study. Residents felt that simulated resuscitations were helpful but anxiety provoking, largely due to interprofessional dynamics. They embraced the interprofessional training opportunity and appreciated hearing other healthcare providers' perspectives, but questioned the value of interprofessional debriefing. They identified the need to maintain positive relationships with colleagues in light of the teams' complex hierarchy as a barrier to candid feedback. DISCUSSION: Pediatric residents in our study appreciated the opportunity to participate in interprofessional team training but were conflicted about the value of feedback and debriefing in this setting. These data indicate that the optimal approach to such interprofessional education activities deserves further study. PMID- 26261116 TI - Building an interfaculty interprofessional education curriculum: what can we learn from the Universite Laval experience? AB - Interprofessional education (IPE) is increasingly recognized as a means to improve practice in health and social care. However, to secure interprofessional learning, it is important to create occasions in prelicensure health and social services curriculum so that students can learn with, from and about each other. This paper presents the process behind the development and implementation of an IPE curriculum in 10 health and social sciences programs by a team of professors from the faculties of medicine, nursing sciences and social sciences at Universite Laval in the province of Quebec, Canada. The pedagogical approach, description of primary objectives and issues related to its implementation in the curriculum programs are also described and discussed. PMID- 26261117 TI - Telemedicine in education: bridging the gap. AB - BACKGROUND: The increasing cost and inequitable access to quality healthcare, coupled with the merger of the information technology and health service sectors, has given rise to the modern field of telemedicine. Telemedicine, meaning medicine at a distance, allows us to transcend geographic and socioeconomic boundaries to deliver high quality care to remote and/or in-need patients. As technology becomes more affordable and a physician shortage looms, telemedicine is gaining attention as a possible solution to healthcare delivery. Simultaneously, telemedicine holds great promise with regard to medical education. Several studies integrating telemedicine in medical education have shown positive outcomes, demonstrating similar or greater efficacy compared with traditional educational methods with high student-reported enthusiasm. Other domestic and international telemedicine projects, largely spearheaded by universities, have also achieved great success. DISCUSSION: In a novel approach, by pairing medical schools with in-need partner communities, utilizing similar faculty resources as traditional learning methods with standardized patients, students can gain valuable experience and skills while serving actual patients. This progressive approach to medical education fosters collaboration, communication, longitudinal care and teaches students needed skills for their future practices as 21 st Century healthcare providers. PMID- 26261118 TI - Instituting a radiology residency scholarly activity program. AB - BACKGROUND: The purpose of this manuscript is to present a newly instituted program for resident scholarly activity that includes a curriculum designed to enhance resident training with regard to research while meeting requirements established by the Accreditation Council for Graduate Medical Education (ACGME), the governing body responsible for regulation of post-graduate medical education and training in the United States. METHODS: A scholarly activity program was designed with the following goals: (i) enhance the academic training environment for our residents; (ii) foster interests in research and academic career paths; (iii) provide basic education on research methodology and presentation skills. To guide program design, an electronic survey was created and distributed to the residents and faculty in the Department of Radiology and Radiological Sciences at the Medical University of South Carolina (MUSC), a 750-bed public teaching hospital in the state of South Carolina in the United States. RESULTS: Survey respondents were in strong support of a required resident scholarly activity project (70% in favor), felt non-traditional projects were valuable (84.1% of respondents), and were proponents of required scholarly activity summary presentations (58%). This program requires that residents engage in a scholarly activity project under the guidance of a mentor. Resident success is maximized through in-house education initiatives focusing on presentation and research skills, protected time to work on the project, and oversight by a radiology research committee. All residents present a summary of their work near the end of their residency training. DISCUSSION: Changes to the radiology resident certification process create an opportunity for incorporating new policies aimed at enhancing resident education. The scholarly activity program outlined in this manuscript is one such initiative designed to meet ACGME requirements, provide an introduction to research, and establish a scholarly activity project requirement. PMID- 26261119 TI - Implementing the patient-centered medical home in residency education. AB - BACKGROUND: In recent years, physician groups, government agencies and third party payers in the United States of America have promoted a Patient-centered Medical Home (PCMH) model that fosters a team-based approach to primary care. Advocates highlight the model's collaborative approach where physicians, mid level providers, nurses and other health care personnel coordinate their efforts with an aim for high-quality, efficient care. Early studies show improvement in quality measures, reduction in emergency room visits and cost savings. However, implementing the PCMH presents particular challenges to physician training programs, including institutional commitment, infrastructure expenditures and faculty training. DISCUSSION: Teaching programs must consider how the objectives of the PCMH model align with recent innovations in resident evaluation now required by the Accreditation Council of Graduate Medical Education (ACGME) in the US. This article addresses these challenges, assesses the preliminary success of a pilot project, and proposes a viable, realistic model for implementation at other institutions. PMID- 26261120 TI - Student participation: to the benefit of both the student and the faculty. AB - Students who actively participate in the evaluation of their undergraduate medical curriculum become important stakeholders in decisions related to the design of the school's curriculum. Research and reports on student participation in curriculum change are scarce, and not much is known about how students personally benefit. We describe the structure and activities of engaging students in designing and improving the curriculum at the Faculty of Medicine and Health Sciences of Ghent University (Belgium). We present an example of a major curriculum change led by students, and we assess the perceptions of the students on how engagement in student curriculum committees strengthened their leadership skills. We encourage students at other schools to become active participants in the curriculum design and improvement processes of their institutions as a way to improve medical education. PMID- 26261121 TI - Let's 'play' with molecular pharmacology. AB - BACKGROUND: Understanding concepts of molecular mechanisms of drug action involves sequential visualization of physiological processes and drug effects, a task that can be difficult at an undergraduate level. Role-play is a teaching learning methodology whereby active participation of students as well as clear visualization of the phenomenon is used to convey complex physiological concepts. However, its use in teaching drug action, a process that demands understanding of a second level of complexity over the physiological process, has not been investigated. We hypothesized that role-play can be an effective and well accepted method for teaching molecular pharmacology. METHODS: In an observational study, students were guided to perform a role-play on a selected topic involving drug activity. Students' gain in knowledge was assessed comparing validated pre- and post-test questionnaires as well as class average normalized gain. The acceptance of role-play among undergraduate medical students was evaluated by Likert scale analysis and thematic analysis of their open-ended written responses. RESULTS: Significant improvement in knowledge (P < 0.001) was noted in the pre- to post-test knowledge scores, while a high gain in class average normalized score was evident. In Likert scale analysis, most students (93%) expressed that role-play was an acceptable way of teaching. In a thematic analysis, themes of both strengths and weaknesses of the session emerged. DISCUSSION: Role-play can be effectively utilized while teaching selected topics of molecular pharmacology in undergraduate medical curricula. PMID- 26261122 TI - Views of practitioners of alternative medicine toward psychiatric illness and psychiatric care: a study from Solapur, India. AB - BACKGROUND: It is common knowledge that patients seek treatment for psychiatric illnesses from various sources including the alternative medicine. Views and attitudes of clinicians often influence the provision of appropriate mental health care for these patients. In this context, it was intended to study the views of the practitioners of alternative medicine toward psychiatric disorders, patients and interventions. METHODS: The study was conducted as a questionnaire based survey among a sample of practitioners of alternative medicine specifically Ayurveda and Homeopathy, who were practicing in Solapur and adjoining areas of Maharashtra and Karnataka states in India. A semi-structured Attitudinal Inventory for Psychiatry questionnaire was used. Demographic and professional data were collected. RESULTS: Out of 62 practitioners approached, 50 responded (80.6%). There were no significant differences in the views of practitioners toward psychiatry and psychiatrists based on respondents' gender, place of residence, location of practice, type of alternative medicine, exposure to psychiatric patients, or if they knew someone with psychiatric illness. Attitudes were generally positive, but variable. Among negative observations were that approximately 60% of respondents felt that a patient can be disadvantaged by being given a psychiatric label and 58% believed that emotions are difficult to handle. A considerable proportion (40%) of the respondents felt doctors other than psychiatrists were unable to identify psychiatric disorders. DISCUSSION: This study's findings suggest that practitioners of alternative medicine have mixed views about mental illness, patients and treatment. Some of their negative views and perceived inability to identify psychiatric disorders may be addressed through further training, information sharing and collaborative work. PMID- 26261123 TI - Factors causing stress among students of a medical college in Kolkata, India. AB - BACKGROUND: Medical students feel a significant amount of stress due to a variety of factors. Few studies have explored the relative size of these various stressors to identify which are most important. This study was undertaken to quantify the magnitude of various sources of stress among students of a medical college at Kolkata, West Bengal, and also to assess the reliability of Medical Students' Stressor Questionnaire (MSSQ-40) in this context. METHODS: We evaluated the degree of stress along various dimensions using the MSSQ-40, a scale to measure stress among medical students that has been validated in other countries. Differences in stress and its causal factors were analyzed across demographic subgroups. The reliability of the MSSQ-40 was evaluated using Cronbach's alpha. RESULTS: The overall prevalence of stress was 91.1% and the vast majority of students (94.9%) were stressed due to academic reasons. Academic related stress was found to be higher among students who are not conversant with the local language, experienced a change in medium of teaching from secondary school to medical school, and resided in a hostel. The MSSQ-40 in general, and its academic related stress domain specifically, were found to be reliable in our setting. DISCUSSION: Early detection and remedying stressors will help to build physical and mental health in medical students. Language training early during the medical course might reduce academic stress among our students. Further studies should relate individuals' stress with their academic performance. PMID- 26261124 TI - Accuracy of body weight perceptions among students in a medical school in Central Delhi, India. AB - BACKGROUND: Body image is an important aspect of the complex creation of one's self-identity. The relationship between nutritional disorders, like obesity, and one's perception of her or his body is well documented. Obesity among medical students and health personnel is on the rise. Identifying and measuring the magnitude of distortion in body image self-perception among medical students is particularly relevant, as they are future healthcare providers. This paper assesses self-perceptions of body mass index (BMI) and physical activity among medical undergraduate students in an Indian medical school. METHODS: A cross sectional study was conducted among 161 sixth semester medical undergraduate students in a school in Delhi, India. A pretested questionnaire was used. Anthropometric measurements were taken. The participation rate was 93.6%. RESULTS: Out of the total 161 students, there were 60.9% males and 39.1% females. Most participants were classified as normal (55.9%) according to BMI. The proportions of actual obese, overweight and underweight students were 4.4%, 30.4% and 9.3%, respectively. However, the proportion of students perceiving themselves as obese or overweight was only 37.3%. A significantly higher proportion of females (57.2%) than males (20.4%) perceived themselves as overweight (P < 0.001). The agreement between actual BMI and perceived weight was poor (kappa statistic: 0.33). Among actual overweight and obese students, only one-third were physically active. CONCLUSIONS: Students who were overweight or obese often failed to perceive themselves as such and, perhaps consequently, were not engaging in weight control practices. There is a need to develop health promotion interventions that help build healthy body habitus perceptions among this group of Indian medical students. PMID- 26261125 TI - Creating a blended learning module in an online master study programme in oncology. AB - BACKGROUND: The medical faculty of Ulm University has launched the postgraduate master online study programme Advanced Oncology (AO) in 2010. We describe the challenges in developing an e-learning module using the example of a medical biometry course, focusing the implementation of the course material and our single-loop learning experience after the first students have finished and evaluated the lecture. METHODS: Programme participants are qualified medical doctors and researchers in biomedical areas related to the field of oncology. The study programme provides the majority of lectures online via didactic videos accompanied by one-week attendance seminars. Supplementary learning materials include review articles, supportive reading material, multiple choice questions, and exercises for each unit. Lecture evaluations based on specific questions concerning learning environment and information learned, each measured on a five point Likert scale. RESULTS: Lecture videos were implemented following the classical triad of the didactic process, using oncological examples from practice to teach. The online tutorial support offered to students was hardly used, thus we enhanced faculty presence during the face-to-face seminars. Lecture evaluations improved after revising the learning material on the basis of the first AO student cohort's comments. DISCUSSION: Developing and implementing an online study programme is challenging with respect of maximizing the information students learn due to limited opportunities for personal contact between lecturers and students. A more direct interaction of lecturers and students in a blended learning setting outperforms a mere web-based contact in terms of learning advantage and students' satisfaction, especially for complex methodological content. PMID- 26261126 TI - Inclusion of basic vitreoretina training in Indian ophthalmology residency programmes - need of the hour! PMID- 26261127 TI - Who is holding us back from providing integrative and holistic health care? PMID- 26261128 TI - An online nutrition in medicine module: an important resource for medical students and physicians. PMID- 26261129 TI - Obstetricians' knowledge, attitudes and practices in oral health and pregnancy. PMID- 26261130 TI - Case-based, team-based learning: a novel method for teaching orofacial syndromology to dental undergraduate students. PMID- 26261131 TI - Peripheral T-cell lymphoma, not otherwise specified with prominent cutaneous involvement. PMID- 26261132 TI - Pemphigus vegetans localized to unusual sites. PMID- 26261133 TI - Unilateral cutaneous vasculitis: An uncommon presentation and a possible explanation. PMID- 26261134 TI - A human case of strangles (equine distemper) with skin lesions. PMID- 26261135 TI - Matchbox sign: Look before you label! PMID- 26261138 TI - Tuberous sclerosis presenting with late onset seizures and scrotal angiofibromas. PMID- 26261139 TI - Failure to detect Mycobacterium lepromatosis as a cause of leprosy in 85 Chinese patients. PMID- 26261140 TI - Recent advances in topical formulation carriers of antifungal agents. AB - Fungal infections are amongst the most commonly encountered diseases affecting the skin. Treatment approaches include both topical and oral antifungal agents. The topical route is generally preferred due to the possible side effects of oral medication. Advances in the field of formulation may soon render outdated conventional products such as creams, ointments and gels. Several carrier systems loaded with antifungal drugs have demonstrated promising results in the treatment of skin fungal infections. Examples of these newer carriers include micelles, lipidic systems such as solid lipid nanoparticles and nanostructured lipid carriers, microemulsions and vesicular systems such as liposomes, niosomes, transfersomes, ethosomes, and penetration enhancer vesicles. PMID- 26261141 TI - Black grain eumycetoma of the breast misdiagnosed as fibroadenoma. PMID- 26261142 TI - Pemphigus foliaceus occurring with adenocarcinoma of prostate. PMID- 26261143 TI - Disseminated cutaneous phaeohyphomycosis due to Cladophialophora bantiana. AB - Cladophialophora bantiana is a neurotropic dematiaceous fungus which only rarely affects the skin. We report a case of disseminated cutaneous phaeohyphomycosis caused by Cladophialophora bantiana in an immunocompromised female who presented with multiple pyogenic granuloma-like nodules, dermatophytosis-like plaque, and subcutaneous cysts on the upper and lower extremities without systemic involvement. Biopsy revealed black yeasts resembling sclerotic bodies and culture yielded irregular, velvety, grey colonies with black reverse. Excision of the nodules and treatment with oral itraconazole 100 mg twice daily resulted in complete clinical resolution within two months, following which itraconazole was administered for another 4 months. PMID- 26261144 TI - Pseudo-lipomatosis cutis: A singular dermal artifact. PMID- 26261145 TI - Fingertip eczema to pooja flowers: Allergic contact dermatitis to Tabernaemontana divaricata and Tecoma stans. PMID- 26261146 TI - Cetirizine-induced urticaria masquerading as multiple drug intolerance syndrome. PMID- 26261147 TI - Papular elastorrhexis. PMID- 26261148 TI - Extrafacial rosacea with predominant scalp involvement. PMID- 26261149 TI - Role of dental restoration materials in oral mucosal lichenoid lesions. AB - BACKGROUND: Dental restorative materials containing silver-mercury compounds have been known to induce oral lichenoid lesions. OBJECTIVES: To determine the frequency of contact allergy to dental restoration materials in patients with oral lichenoid lesions and to study the effect of removal of the materials on the lesions. RESULTS: Forty-five patients were recruited in three groups of 15 each: Group A (lesions in close contact with dental materials), Group B (lesions extending 1 cm beyond the area of contact) and Group C (no topographic relationship). Thirty controls were recruited in two groups of 15 individuals each: Group D (oral lichenoid lesions but no dental material) and Group E (dental material but no oral lichenoid lesions). Patch tests were positive in 20 (44.5%) patients. Mercury was the most common allergen to elicit a positive reaction in eight patients, followed by nickel (7), palladium (5), potassium dichromate (3), balsam of Peru, gold sodium thiosulphate 2 and tinuvin (2) and eugenol (1), cobalt chloride (1) and carvone (1). Seven patients elicited positive response to more than one allergen. In 13 of 20 patients who consented to removal of the dental material, complete healing was observed in 6 (30%), marked improvement in 7 (35%) and no improvement in 7 (35%) patients. Relief of symptoms was usually observed 3 months after removal. LIMITATIONS: Limited number of study subjects and short follow up after removal/replacement of dental restoration materials are the main limitations of this study. CONCLUSION: Contact allergy to amalgam is an important etiologic factor in oral lichenoid lesions and removal of restorative material should be offered to patients who have lesions in close proximity to the dental material. PMID- 26261150 TI - Palatal ecchymosis associated with irrumation. PMID- 26261151 TI - Dermato-neuro syndrome associated with scleromyxedema. PMID- 26261154 TI - Three cases of suspected chloracne in a family from Pune. PMID- 26261155 TI - Considerations when communicating with awake patients undergoing image-guided neuro-interventions. AB - The authors empirically evaluated the context of intra-procedural physician patient communication during imaging-guided procedures in a radiology/neuroradiology interventional clinical framework. Different intra procedural communicative scenarios are reported.They conclude that the quality of intra-procedural physician-patient communication should be considered an important element of individual and team ethical and professional behaviour, able to strongly influence the therapeutic alliance. As for the whole medical communication strategy, an approach which takes into account the psychological and cultural background of the individual patient is preferred. PMID- 26261157 TI - Chronic pacing and adverse outcomes after transcatheter aortic valve implantation. AB - OBJECTIVE: Many patients undergoing transcatheter aortic valve implantation (TAVI) have a pre-existing, permanent pacemaker (PPM) or receive one as a consequence of the procedure. We hypothesised that chronic pacing may have adverse effects on TAVI outcomes. METHODS AND RESULTS: Four groups of patients undergoing TAVI in the Placement of Aortic Transcatheter Valves (PARTNER) trial and registries were compared: prior PPM (n=586), new PPM (n=173), no PPM (n=1612), and left bundle branch block (LBBB)/no PPM (n=160). At 1 year, prior PPM, new PPM and LBBB/no PPM had higher all-cause mortality than no PPM (27.4%, 26.3%, 27.7% and 20.0%, p<0.05), and prior PPM or new PPM had higher rehospitalisation or mortality/rehospitalisation (p<0.04). By Cox regression analysis, new PPM (HR 1.38, 1.00 to 1.89, p=0.05) and prior PPM (HR 1.31, 1.08 to 1.60, p=0.006) were independently associated with 1-year mortality. Surviving prior PPM, new PPM and LBBB/no PPM patients had lower LVEF at 1 year relative to no PPM (50.5%, 55.4%, 48.9% and 57.6%, p<0.01). Prior PPM had worsened recovery of LVEF after TAVI (Delta=10.0 prior vs 19.7% no PPM for baseline LVEF <35%, p<0.0001; Delta=4.1 prior vs 7.4% no PPM for baseline LVEF 35-50%, p=0.006). Paced ECGs displayed a high prevalence of RV pacing (>88%). CONCLUSIONS: In the PARTNER trial, prior PPM, along with new PPM and chronic LBBB patients, had worsened clinical and echocardiographic outcomes relative to no PPM patients, and the presence of a PPM was independently associated with 1-year mortality. Ventricular dyssynchrony due to chronic RV pacing may be mechanistically responsible for these findings. TRIAL REGISTRATION NUMBER: (ClinicalTrials.gov NCT00530894). PMID- 26261159 TI - Child sexual abuse: Issues & concerns. PMID- 26261158 TI - Estimated 10-year cardiovascular mortality seriously underestimates overall cardiovascular risk. AB - OBJECTIVE: The European Society of Cardiology's prevention guideline suggests that the risk of total (fatal plus non-fatal) cardiovascular disease (CVD) may be calculated from the risk of CVD mortality using a fixed multiplier (3*). However, the proposed multiplier has not been validated. We investigated the ratio of total CVD to CVD mortality in a large population-based cohort. METHODS: CVD mortality and total CVD (fatal plus non-fatal CVD requiring hospitalisation) were analysed using Kaplan-Meier estimates among 24 014 men and women aged 39-79 years without baseline CVD or diabetes mellitus in the prospective population-based European Prospective Investigation of Cancer and Nutrition-Norfolk cohort. CVD outcomes included death and hospitalisations for ischaemic heart disease, heart failure, cerebrovascular disease, peripheral artery disease or aortic aneurysm. The main study outcome was the ratio of 10-year total CVD to 10-year CVD mortality stratified by age and sex. RESULTS: Ten year CVD mortality was 3.9% (900 CVD deaths, 95% CI 3.6% to 4.1%); the rate of total CVD outcomes was 21.2% (4978 fatal or non-fatal CVD outcomes, 95% CI 20.7% to 21.8%). The overall ratio of total CVD to CVD mortality was 5.4. However, we found major differences in this ratio when stratified by gender and age. In young women (39-50 years), the ratio of total CVD to CVD mortality was 28.5, in young men (39-50 years) 11.7. In the oldest age group, these ratios were considerably lower (3.2 in women and 2.4 in men aged 75-79 years). CONCLUSIONS: The relationship between 10-year total CVD and CVD mortality is dependent on age and sex, and cannot be estimated using a fixed multiplier. Using CVD mortality to estimate total CVD risk leads to serious underestimation of risk, particularly in younger age groups, and particularly in women. PMID- 26261160 TI - Inventory of a reservoir: friends & foes. PMID- 26261161 TI - Drug induced diseases (DID): Need for more awareness & research. PMID- 26261162 TI - Leptospirosis among the self-supporting convicts of Andaman Island during the 1920s--the first report on pulmonary haemorrhage in leptospirosis? AB - Several researchers had carried out investigations on the possibility of existence of Weil's disease in Andaman Islands during early 20 th century. The first report of a series of confirmed cases of leptospirosis that occurred during 1929 was published in 1931.There were several reports during 1995 to 2009 that described detailed account of leptospirosis including various clinical syndromes. The possibility of pulmonary involvement in leptospirosis being a manifestation historically overlooked rather than newly emerged during the past two decades is examined in this review in the context of Andaman Islands. Two case series of leptospirosis, one occurred in 1929 and the other in 1996-1997 were reviewed with special emphasis on pulmonary involvement and haemorrhagic manifestations. The similarities and differences in the clinical profile of patients of the two case series were analysed. The review shows that respiratory system involvement and pulmonary haemorrhage as evidenced by presence of haemoptysis as a complication of leptospirosis was occurring during 1920s in Andaman Islands. The incidence of pulmonary involvement, however, rose from 9.4 per cent during 1929 to 52 per cent in 1996-1997. The case fatality ratio in patients with pulmonary involvement, which was 50 per cent during 1929 and 42.9 per cent during 1996-1997, was higher than that in cases without pulmonary involvement.Fever, conjunctival congestion, jaundice, vomiting, diarrhoea, hepatomagaly, haemoptysis, haematemesis and subconjunctival haemorrhage were common in both series. The case series in Andaman Islands in 1929 was probably the first report of pulmonary haemorrhage as a manifestation of leptospirosis. The increase in the incidence of pulmonary involvement in leptospirosis in the recent past is probably due to the increase in the density and diversity of its animal vectors,the broadening of the range of circulating serovars and the interactions between the vector and the agent. An increased virulence of Leptospira through gene acquisition and loss on an evolutionary time scale and the resulting change in the gene content, gene order and gene expression cannot be ruled out. PMID- 26261163 TI - Alterations of mucosal microbiota in the colon of patients with inflammatory bowel disease revealed by real time polymerase chain reaction amplification of 16S ribosomal ribonucleic acid. AB - BACKGROUND & OBJECTIVES: Alterations in microbial communities closely associated with the intestinal mucosa are likely to be important in the pathogenesis of inflammatory bowel disease (IBD). We examined the abundance of specific microbial populations in colonic mucosa of patients with ulcerative colitis (UC), Crohn's disease (CD) and controls using reverse transcription quantitative polymerase chain reaction (RT-qPCR) amplification of 16S ribosomal ribonucleic acid (16S rRNA). METHODS: RNA was extracted from colonic mucosal biopsies of patients with UC (32), CD (28) and patients undergoing screening colonoscopy (controls), and subjected to RT-qPCR using primers targeted at 16S rRNA sequences specific to selected microbial populations. RESULTS: Bacteroides-Prevotella-Porphyromonas group and Enterobacteriaceae were the most abundant mucosal microbiota. Bacteroides and Lactobacillus abundance was greater in UC patients compared with controls or CD. Escherichia coli abundance was increased in UC compared with controls. Clostridium coccoides group and C. leptum group abundances were reduced in CD compared with controls. Microbial population did not differ between diseased and adjacent normal mucosa, or between untreated patients and those already on medical treatment. The Firmicutes to Bacteroidetes ratio was significantly decreased in both UC and CD compared with controls, indicative of a dysbiosis in both conditions. INTERPRETATION & CONCLUSIONS: Dysbiosis appears to be a primary feature in both CD and UC. Microbiome-directed interventions are likely to be appropriate in therapy of IBD. PMID- 26261164 TI - Drug-induced diseases (DIDs): An experience of a tertiary care teaching hospital from India. AB - BACKGROUND & OBJECTIVES: Drug-induced diseases (DIDs) are well known but least studied. Data on DIDs from India are not available. Hence, this retrospective cross-sectional study was undertaken using suspected adverse drug reaction (ADR) data collected form Pharmacovigilance Programme of India (PvPI) to evaluate profile of DIDs over two years, in a tertiary care teaching hospital from north India. METHODS: The suspected ADRs in the form of DID were evaluated for drug and disease related variables and were classified in terms of causality. RESULTS: DID rate was 38.80 per cent. Mean duration of developing DIDs was 26.05 +/- 9.6 days; 25.16 per cent had more than one co-morbid condition. Geriatric population (53.99%) accounted for maximum DIDs followed by adult (37.79%) and paediatric (8.21%). Maximum events were probable (93.98%) followed by possible (6.04%). All DIDs required intervention. Gastritis (7.43%), diarrhoea (5.92%), anaemia (4.79%), hypotension (2.77%), hepatic dysfunction (2.69%), hypertension (1.51%), myalgia (1.05%), and renal dysfunction (1.01%) were some of the DIDs. Anti tubercular treatment (ATT), anti retroviral treatment (ART), ceftriaxone injection, steroids, non-steroidal anti-inflammatory drugs, antimicrobials and anticancer drugs were found as commonly offending drugs. INTERPRETATION & CONCLUSIONS: Our findings show that DIDs are a significant health problem in our country, which need more attention. PMID- 26261165 TI - Association of serotonin transporter (SLC6A4) and receptor (5HTR1A, 5HTR2A) polymorphisms with response to treatment with escitalopram in patients with major depressive disorder: A preliminary study. AB - BACKGROUND & OBJECTIVES: Genetic factors have potential of predicting response to antidepressants in patients with major depressive disorder (MDD). In this study, an attempt was made to find an association between response to escitalopram in patients with MDD, and serotonin transporter (SLC6A4) and receptor (5HTR1A, 5HTR2A) polymorphisms. METHODS: Fifty five patients diagnosed as suffering from MDD, were selected for the study. The patients were treated with escitalopram over a period of 6-8 wk. Severity of depression, response to treatment and side effects were assessed using standardised instruments. Genetic variations from HTR1A (rs6295), HTR2A (rs6311 and rs6313) and SLC6A4 (44 base-pair insertion/deletion at 5-HTTLPR) were genotyped. The genetic data of the responders and non-responders were compared to assess the role of genetic variants in therapeutic outcome. RESULTS: Thirty six (65.5%) patients responded to treatment, and 19 (34.5%) had complete remission. No association was observed for genotype and allelic frequencies of single nucleotide polymorphisms (SNPs) among remitter/non-remitter and responder/non-responder groups, and six most common side-effects, except memory loss which was significantly associated with rs6311 ( p0 =0.03). INTERPRETATION & CONCLUSIONS: No significant association was found between the SNPs analysed and response to escitalopram in patients with MDD though a significant association was seen between the side effect of memory loss and rs6311. Studies with larger sample are required to find out genetic basis of antidepressant response in Indian patients. PMID- 26261166 TI - A preliminary study of inherited thrombophilic risk factors in different clinical manifestations of venous thromboembolism in central Iran. AB - BACKGROUND & OBJECTIVES: Inherited thrombophilia is known to be an important risk factor for developing venous thromboembolism. Whether such abnormalities may impact the development of deep vein thrombosis (DVT) and pulmonary embolism (PE) differently is not well defined. This preliminary study was undertaken to compare thrombophilic polymorphism in patients with DVT and PE. METHODS: A total of 35 DVT, 23 DVT/PE, and 37 PE patients admitted to the Hajar Hospital, Shahrekord, Iran, between October 2009 and February 2011 were included in the study and 306 healthy volunteers matched by age and sex from the same geographical area with no history of venous or arterial diseases were included as control group. Factor V Leiden (FV 1691G/A, rs6025), prothrombin (FII 20210G/A), methylene tetrahydrofulate reductase (MTHFR 677C/T, rs1801133), and PLA2 polymorphisms of platelet glycoprotein IIb/IIIa (GpIIIa 1565T/C, rs5918) were investigated by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The number of patients with the investigated polymorphisms and homozygous carriers was significantly different among the groups (P<0.05). No significant difference was observed in the presence of FV 1691G/A and FII 20210G/A between any of the patients groups and the control group. GpIIIa 1565T/C and homozygous MTHFR 677C/T polymorphisms were higher in DVT patients compared with the control group (OR=6.65, 95% CI=3.09-14.30 and OR=4.08, 95% CI=1.35-12.38, respectively). INTERPRETATION & CONCLUSIONS: As none of the investigated polymorphisms were associated with PE, other thrombophilia polymorphisms may have a role in the pathogenesis of PE in these patients and should be investigated. Because of different prognostic risk factors among different types of patients, the treatment approach could be different. PMID- 26261167 TI - Immunological & metabolic responses to a therapeutic course of Basti in obesity. AB - BACKGROUND & OBJECTIVES: Basti (medicated enema) is a popular Ayurvedic intervention recommended for obesity. However, there are no data to show whether any physiological or biochemical changes occur following this treatment. This study was conducted to identify the immunological and metabolic changes in obese individuals after a therapeutic course of Basti. METHODS: Thirty two obese individuals (18 and 60 yr) with a body mass index (BMI) >=30 kg/m [2] who received a therapeutic course of 16 enemas (Basti) followed by a specific diet and lifestyle regimen for a period of 32 days as their treatment for obesity, were enrolled in the study. Clinical examination, measurement of immune and metabolic markers were done before (S1), immediately after (S2) and 90 days after the completion of therapy (S3). RESULTS: A significant reduction ( P<0.001) in weight, BMI, upper arm and abdominal circumference was seen at S3, along with a decrease in serum interferon (IFN)-gamma (P<0.02), interleukin (IL)-6 ( P<0.02) and ferritin (P<0.05) and increase in IgM levels ( P<0.02). Peripheral blood lymphocytes (PBLs) stimulated with anti-CD3 monoclonal antibodies showed significant increase in reactive oxygen species (ROS) generation and calcium flux after Basti. All organ function tests revealed no changes. INTERPRETATION & CONCLUSIONS: Our study documents that a therapeutic course of Basti modulates immune responses by regulating pro-inflammatory cytokines, immunoglobulins and functional properties of T-cells. These changes are associated with a reduction in the body weight which is maintained even after three months of treatment. The study also documents the safety of Basti procedure. PMID- 26261168 TI - Effect of mesenchymal stem cells transplantation on glycaemic profile & their localization in streptozotocin induced diabetic Wistar rats. AB - BACKGROUND & OBJECTIVES: Bone marrow is a rich source of adult stem cells that can differentiate into various cell types. Administration of mesenchymal stem cells (MSCs) in irradiated diabetic rat model has transiently shown to decrease blood glucose level. This study examines the effect of high dose and multiple injections of MSCs on glycemic profile, their localization and regeneration of islet in diabetic Wistar rat. METHODS: The study was carried out in male Wistar rats categorized into three groups (n=6, in each group): Group 1 as control, group 2 streptozotocin (STZ) (50 mg/kg) induced diabetic group and group 3 experimental group; 5-bromo-2-deoxyuridine (BrdU) labelled allogenic MSCs were injected in the non-irradiated diabetic rat of the experimental group through tail vein. The blood glucose profile was subsequently monitored at regular intervals. Rats were sacrificed on day 45 and pancreas was examined for localization of BrdU labelled stem cells by immunofluorescence and islet neogenesis by immunohistochemistry . RESULTS: There was a significant reduction in blood glucose level after administration of MSCs in the experimental group (P<0.001). The presence of BrdU labelled MSCs in islet suggested their localization in the pancreas. Co-expression of anti-BrdU and anti-insulin antibody indicated trans-differentiation / fusion into insulin producing cells evidenced by significant increase in total number of islet (P=0.004) and insulin positive cells ( P<0.0001) in experimental group. INTERPRETATION & CONCLUSIONS: Our results showed that the MSCs administration in non-irradiated diabetic Wistar rat reduced hyperglycaemia and was accompanied by increased islet-neogenesis, possibly through trans-differentiation/fusion. PMID- 26261169 TI - Complete genome sequence of two genotype III Japanese encephalitis virus isolates from West Bengal, India. AB - BACKGROUND & OBJECTIVES: Japanese encephalitis (JE), caused by a mosquito-borne virus JE virus (JEV), is a serious health problem in West Bengal, India. In this study, we report the complete genome sequence of two JEV isolates from West Bengal. The amino acid and nucleotide sequence homology was compared with other Indian strains. METHODS: Two JEV isolates (IND-WB-JE1 and IND-WB-JE2) obtained in 2008 and 2010, respectively, from two districts of the State of West Bengal, respectively were analyzed for genetic variations by sequencing the 10934 bp whole genome of the virus. Of these two districts, one was covered under JE vaccination programme in 2007. RESULTS: Phylogenetic analysis showed that both the isolates belonged to the genotype III. A total of 16 mutations were identified in the two isolates studied with respect to Vellore P20778 strain. One unique mutation A3215S was only found in IND-WB-JE2 isolate, but not in the isolate IND-WB-JE1. These two isolates showed maximum homology with P20778 strain of India. INTERPRETATION & CONCLUSIONS: This study reports on complete gene based phylogenetic analysis of JEV isolates from the State of West Bengal. It was evident from the results that JEV was still under circulation in both vaccine covered and not covered districts of West Bengal. PMID- 26261170 TI - Evaluation of profertility effect of probiotic Lactobacillus plantarum 2621 in a murine model. AB - BACKGROUND & OBJECTIVES: Urogenital infections of bacterial origin have a high incidence among the female population at reproductive age, affecting the fertility. Strains of Escherichia coli can colonize the vagina and replace natural microflora. Lactobacillus the predominant vaginal microorganism in healthy women, maintains the acidic vaginal pH which inhibits pathogenic microorganisms. Studies on Lactobacillus have shown that these can inhibit E. coli growth and vaginal colonization. An alternative therapeutic approach to antimicrobial therapy is to re-establish Lactobacillus in this microbiome through probiotic administration to resurge fertility. Therefore, the aim of the present study was to determine the capability of L. plantarum 2621 strain with probiotic properties, to prevent the vaginal colonization of E. coli causing agglutination of sperms and to evaluate its profertility effect in a murine model. METHODS: Screened mice were divided into five groups i.e. control group, E. coli group, Lactobacillus group, prophylactic and therapeutic groups. The control group was infused with 20 ul PBS, E.coli group was administered with 10 [6] cfu/20 ul E. coli, and probiotic group was administered with Lactobacillus (10 [8] cfu/20 ul) for 10 consecutive days. In prophylactic group, the vagina was colonized with 10 consecutive doses of Lactobacillus (10 [8] cfu/20 ul). After 24 h, it was followed by 10 day intravaginal infection with E. coli (10 [6] cfu/20 ul) whereas for the therapeutic group vagina was colonized with (10 [6] cfu/20 ul) E. coli for 10 consecutive days, followed by 10 day intravaginal administration with Lactobacillus after 24 h. RESULTS: Upon mating and completion of gestation period, control, probiotic and the therapeutic groups had litters in contrast to the prophylactic group and the group administered with E. coli. INTERPRETATION & CONCLUSIONS: Results indicated that Lactobacillus intermitted colonization of pathogenic strains that resulted in reinforcement of natural microflora and resurge fertility. PMID- 26261171 TI - High heterozygosity frequency of three exonic SNPs of factor V gene (F5): implications for genetic diagnosis. PMID- 26261172 TI - Real time PCR reconfirmed three novel clinical associations of parvovirus B19: Non-occlusive bowel gangrene, amegakaryocytic thrombocytopenia & myositis. PMID- 26261173 TI - Selective digestive decontamination saves lives whilst preventing resistance. PMID- 26261174 TI - Authors' response. PMID- 26261175 TI - Confounding in case control studies. PMID- 26261176 TI - Authors' response. PMID- 26261177 TI - An unusual foreign body. PMID- 26261178 TI - Multiple jejunal diverticula causing intestinal obstruction. PMID- 26261179 TI - MicroRNA-7/NF-kappaB signaling regulatory feedback circuit regulates gastric carcinogenesis. AB - MicroRNAs play essential roles in gene expression regulation during carcinogenesis. Here, we investigated the role of miR-7 and the mechanism by which it is dysregulated in gastric cancer (GC). We used genome-wide screenings and identified RELA and FOS as novel targets of miR-7. Overexpression of miR-7 repressed RELA and FOS expression and prevented GC cell proliferation and tumorigenesis. These effects were clinically relevant, as low miR-7 expression was correlated with high RELA and FOS expression and poor survival in GC patients. Intriguingly, we found that miR-7 indirectly regulated RELA activation by targeting the IkappaB kinase IKKepsilon. Furthermore, IKKepsilon and RELA can repress miR-7 transcription, which forms a feedback circuit between miR-7 and nuclear factor kappaB (NF-kappaB) signaling. Additionally, we demonstrate that down-regulation of miR-7 may occur as a result of the aberrant activation of NF kappaB signaling by Helicobacter pylori infection. These findings suggest that miR-7 may serve as an important regulator in GC development and progression. PMID- 26261180 TI - Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD like pathogenesis. AB - The degradation of phagosomes, derived from the ingestion of photoreceptor outer segment (POS) disk membranes, is a major role of the retinal pigment epithelium (RPE). Here, POS phagosomes were observed to associate with myosin-7a, and then kinesin-1, as they moved from the apical region of the RPE. Live-cell imaging showed that the phagosomes moved bidirectionally along microtubules in RPE cells, with kinesin-1 light chain 1 (KLC1) remaining associated in both directions and during pauses. Lack of KLC1 did not inhibit phagosome speed, but run length was decreased, and phagosome localization and degradation were impaired. In old mice, lack of KLC1 resulted in RPE pathogenesis that was strikingly comparable to aspects of age-related macular degeneration (AMD), with an excessive accumulation of RPE and sub-RPE deposits, as well as oxidative and inflammatory stress responses. These results elucidate mechanisms of POS phagosome transport in relation to degradation, and demonstrate that defective microtubule motor transport in the RPE leads to phenotypes associated with AMD. PMID- 26261181 TI - alpha-Catenin-mediated cadherin clustering couples cadherin and actin dynamics. AB - The function of the actin-binding domain of alpha-catenin, alphaABD, including its possible role in the direct anchorage of the cadherin-catenin complex to the actin cytoskeleton, has remained uncertain. We identified two point mutations on the alphaABD surface that interfere with alphaABD binding to actin and used them to probe the role of alpha-catenin-actin interactions in adherens junctions. We found that the junctions directly bound to actin via alphaABD were more dynamic than the junctions bound to actin indirectly through vinculin and that recombinant alphaABD interacted with cortical actin but not with actin bundles. This interaction resulted in the formation of numerous short-lived cortex-bound alphaABD clusters. Our data suggest that alphaABD clustering drives the continuous assembly of transient, actin-associated cadherin-catenin clusters whose disassembly is maintained by actin depolymerization. It appears then that such actin-dependent alphaABD clustering is a unique molecular mechanism mediating both integrity and reassembly of the cell-cell adhesive interface formed through weak cis- and trans-intercadherin interactions. PMID- 26261182 TI - Non-muscle myosin IIB is critical for nuclear translocation during 3D invasion. AB - Non-muscle myosin II (NMII) is reported to play multiple roles during cell migration and invasion. However, the exact biophysical roles of different NMII isoforms during these processes remain poorly understood. We analyzed the contributions of NMIIA and NMIIB in three-dimensional (3D) migration and in generating the forces required for efficient invasion by mammary gland carcinoma cells. Using traction force microscopy and microfluidic invasion devices, we demonstrated that NMIIA is critical for generating force during active protrusion, and NMIIB plays a major role in applying force on the nucleus to facilitate nuclear translocation through tight spaces. We further demonstrate that the nuclear membrane protein nesprin-2 is a possible linker coupling NMIIB based force generation to nuclear translocation. Together, these data reveal a central biophysical role for NMIIB in nuclear translocation during 3D invasive migration, a result with relevance not only to cancer metastasis but for 3D migration in other settings such as embryonic cell migration and wound healing. PMID- 26261184 TI - Endocytosis-dependent coordination of multiple actin regulators is required for wound healing. PMID- 26261183 TI - Shootin1-cortactin interaction mediates signal-force transduction for axon outgrowth. AB - Motile cells transduce environmental chemical signals into mechanical forces to achieve properly controlled migration. This signal-force transduction is thought to require regulated mechanical coupling between actin filaments (F-actins), which undergo retrograde flow at the cellular leading edge, and cell adhesions via linker "clutch" molecules. However, the molecular machinery mediating this regulatory coupling remains unclear. Here we show that the F-actin binding molecule cortactin directly interacts with a clutch molecule, shootin1, in axonal growth cones, thereby mediating the linkage between F-actin retrograde flow and cell adhesions through L1-CAM. Shootin1-cortactin interaction was enhanced by shootin1 phosphorylation by Pak1, which is activated by the axonal chemoattractant netrin-1. We provide evidence that shootin1-cortactin interaction participates in netrin-1-induced F-actin adhesion coupling and in the promotion of traction forces for axon outgrowth. Under cell signaling, this regulatory F actin adhesion coupling in growth cones cooperates with actin polymerization for efficient cellular motility. PMID- 26261185 TI - The Confluence of Sugar, Dental Caries, and Health Policy. PMID- 26261186 TI - Diet and Dental Caries: The Pivotal Role of Free Sugars Reemphasized. AB - The importance of sugars as a cause of caries is underemphasized and not prominent in preventive strategies. This is despite overwhelming evidence of its unique role in causing a worldwide caries epidemic. Why this neglect? One reason is that researchers mistakenly consider caries to be a multifactorial disease; they also concentrate mainly on mitigating factors, particularly fluoride. However, this is to misunderstand that the only cause of caries is dietary sugars. These provide a substrate for cariogenic oral bacteria to flourish and to generate enamel-demineralizing acids. Modifying factors such as fluoride and dental hygiene would not be needed if we tackled the single cause--sugars. In this article, we demonstrate the sensitivity of cariogenesis to even very low sugars intakes. Quantitative analyses show a log-linear dose-response relationship between the sucrose or its monosaccharide intakes and the progressive lifelong development of caries. This results in a substantial dental health burden throughout life. Processed starches have cariogenic potential when accompanying sucrose, but human studies do not provide unequivocal data of their cariogenicity. The long-standing failure to identify the need for drastic national reductions in sugars intakes reflects scientific confusion partly induced by pressure from major industrial sugar interests. PMID- 26261187 TI - Computational analysis of protein interaction networks for infectious diseases. AB - Infectious diseases caused by pathogens, including viruses, bacteria and parasites, pose a serious threat to human health worldwide. Frequent changes in the pattern of infection mechanisms and the emergence of multidrug-resistant strains among pathogens have weakened the current treatment regimen. This necessitates the development of new therapeutic interventions to prevent and control such diseases. To cater to the need, analysis of protein interaction networks (PINs) has gained importance as one of the promising strategies. The present review aims to discuss various computational approaches to analyse the PINs in context to infectious diseases. Topology and modularity analysis of the network with their biological relevance, and the scenario till date about host pathogen and intra-pathogenic protein interaction studies were delineated. This would provide useful insights to the research community, thereby enabling them to design novel biomedicine against such infectious diseases. PMID- 26261188 TI - Anthropometric trends and the risk of cardiovascular disease mortality in a Lithuanian urban population aged 45-64 years. AB - AIMS: To estimate trends in anthropometric indexes from 1992 to 2008 and to evaluate the risk of cardiovascular disease mortality in relation to anthropometric indexes (body mass index, waist circumference, waist:hip ratio, waist:height ratio). METHODS: Data from the three surveys (1992-2008) are presented. A random sample of 5147 subjects aged 45-64 years was selected for statistical analysis. During follow-up there were 141 deaths from cardiovascular disease (excluding those with cardiovascular disease at entry). Cox's regression was used to estimate the associations between anthropometric indexes and cardiovascular disease mortality. RESULTS: During a 17-year period among men, the prevalence of obesity (body mass index ? 30 kg/m(2)) increased from 18.4% to 32.1% (p < 0.001) and a high level of waist:hip ratio (> 0.9) from 59.3% to 72.9% (p < 0.001). The risk profile of obesity did not change in women, but prevalence of a high level of waist:hip ratio (> 0.85) increased from 25.9% to 41.5% (p < 0.001). Multivariable-adjusted Cox's regression models showed that body mass index, waist circumference, waist:hip ratio, waist:height ratio were associated with cardiovascular disease mortality risk only in men (hazard ratios 1.40, 1.45, 1.49, 1.46 respectively (p < 0.01)). CONCLUSIONS: Our data indicate that anthropometric measures such as body mass index, waist circumference, waist:hip ratio and waist:height ratio are good indicators of cardiovascular disease mortality risk only in men aged 45-64 years. PMID- 26261189 TI - Why did life expectancy in Central and Eastern Europe suddenly improve in the 1990s? An analysis by cause of death. AB - BACKGROUND: The upturn of life expectancy in Central and Eastern Europe in the 1990s, after a period of stagnation or even decline, is one of the main events in European population history of the late 20th century, but has not been satisfactorily explained. DATA AND METHODS: Turning points in total and cause specific mortality in the Czech Republic, Bulgaria, Hungary, Poland, Romania and Slovakia were determined using joinpoint regression. Changes in life expectancy in the 10 years following country-specific turning points were decomposed by age and cause of death using Arriaga's method. RESULTS: Among men, the turning points for all-cause mortality coincided with those for ischaemic heart disease in all six countries, and sometimes also with those for liver cirrhosis, road traffic accidents and lung cancer. Among women, the pattern was more diffuse. In the 10 years since the turning point for all-cause mortality, life expectancy increased by around four years for men and three years for women in most countries. Declines in mortality from cardiovascular disease explain between a third and a half of the increase in life expectancy in all countries, but beyond this the contributing causes of death often varied considerably. CONCLUSIONS: Although the upturn of life expectancy in Central and Eastern Europe started at different points in time, improvements in prevention and/or treatment of ischaemic heart disease appear to have played a role in all six countries. Other factors, such as changes in alcohol consumption and road traffic safety, have, however, also made important contributions in some countries. PMID- 26261190 TI - Effect of physical exercise on workplace social capital: Cluster randomized controlled trial. AB - AIMS: While workplace health promotion with group-based physical exercise can improve workers' physical health, less is known about potential carry-over effects to psychosocial factors. This study investigates the effect of physical exercise on social capital at work. METHODS: Altogether, 200 female healthcare workers (nurses and nurse's aides) from 18 departments at three hospitals were randomly allocated at the department level to 10 weeks of (1) group-based physical exercise at work during working hours or (2) physical exercise at home during leisure time. At baseline and follow-up, participants replied to a questionnaire concerning workplace social capital: (1) within teams (bonding); (2) between teams (bridging); (3) between teams and nearest leaders (linking A); (4) between teams and distant leaders (linking B). RESULTS: At baseline, bonding, bridging, linking A and linking B social capital were 74 (SD 17), 61 (SD 19), 72 (SD 22) and 70 (SD 18), respectively, on a scale of 0-100 (where 100 is best). A group by time interaction was found for bonding social capital (P=0.02), where physical exercise at work compared with physical exercise during leisure time increased 5.3 (95% confidence interval 2.3- 8.2)(effect size, Cohen's d = 0.31) from baseline to follow-up. For physical exercise at home during leisure time and exercise at work combined, a time effect (P=0.001) was found for linking A social capital, with a decrease of 4.8 (95% confidence interval 1.9-7.6). CONCLUSIONS: Group-based physical exercise at work contributed to building social capital within teams at the workplace. However, the general decrease of social capital between teams and nearest leaders during the intervention period warrants further research. PMID- 26261191 TI - Variations in life expectancy in Organization for Economic Co-operation and Development countries--1985-2010. AB - AIM: We examined the impact of different behavioral factors of health on the variations in the levels and rate of increase in life expectancy in Organization for Economic Co-operation and Development countries between 1985 and 2010. METHODS: Using the World Health Organization's conceptual framework of socio economic determinants of health, we incorporated Organization for Economic Co operation and Development, World Bank and United Nations data to estimate the impact of these variables on life expectancy for 30 Organization for Economic Co operation and Development countries. We used a random effect model to control the fixed effect of year and each country. RESULTS: Results show that the level of health care spending is the most important factor predicting life expectancy. Other important factors are gross domestic product per capita, labor productivity, years of schooling and percentage of gross domestic product spending allocated for public services. Life expectancy was reduced by smoking and higher daily calorie consumption. Countries that were previously part of the Soviet Union had lower life expectancies. Political factors had only a minor impact on life expectancy. CONCLUSIONS: Life expectancy increased an average of 5.1 years in Organization for Economic Co-operation and Development countries between 1985 and 2010, but there was wide variation. Health spending per capita, economic factors and two behavioral factors - smoking and caloric intake - explained most of the variation and suggest where increased policy attention could have the greatest impact on life expectancy. Policymakers who consider our estimates recognize that they may see greater or less impact depending on the characteristics of their nation. PMID- 26261192 TI - Lemierre syndrome: early recognition and management. PMID- 26261193 TI - Coronary computed tomography angiography. PMID- 26261194 TI - Hidradenitis suppurativa. PMID- 26261195 TI - The cannabis doctor is in. PMID- 26261196 TI - CIHR cutting MD/PhD training program. PMID- 26261197 TI - Central funding for Cochrane Canada must continue. PMID- 26261198 TI - Lessons from Ebola bring WHO reforms. PMID- 26261199 TI - Association between household food insecurity and annual health care costs. AB - BACKGROUND: Household food insecurity, a measure of income-related problems of food access, is growing in Canada and is tightly linked to poorer health status. We examined the association between household food insecurity status and annual health care costs. METHODS: We obtained data for 67 033 people aged 18-64 years in Ontario who participated in the Canadian Community Health Survey in 2005, 2007/08 or 2009/10 to assess their household food insecurity status in the 12 months before the survey interview. We linked these data with administrative health care data to determine individuals' direct health care costs during the same 12-month period. RESULTS: Total health care costs and mean costs for inpatient hospital care, emergency department visits, physician services, same day surgeries, home care services and prescription drugs covered by the Ontario Drug Benefit Program rose systematically with increasing severity of household food insecurity. Compared with total annual health care costs in food-secure households, adjusted annual costs were 16% ($235) higher in households with marginal food insecurity (95% confidence interval [CI] 10%-23% [$141-$334]), 32% ($455) higher in households with moderate food insecurity (95% CI 25%-39% [$361 $553]) and 76% ($1092) higher in households with severe food insecurity (95% CI 65%-88% [$934-$1260]). When costs of prescription drugs covered by the Ontario Drug Benefit Program were included, the adjusted annual costs were 23% higher in households with marginal food insecurity (95% CI 16%-31%), 49% higher in those with moderate food insecurity (95% CI 41%-57%) and 121% higher in those with severe food insecurity (95% CI 107%-136%). INTERPRETATION: Household food insecurity was a robust predictor of health care utilization and costs incurred by working-age adults, independent of other social determinants of health. Policy interventions at the provincial or federal level designed to reduce household food insecurity could offset considerable public expenditures in health care. PMID- 26261200 TI - The Multidisciplinary Team Conference's Decision on M-Staging in Patients with Gastric- and Gastroesophageal Cancer is not Accurate without Staging Laparoscopy. AB - BACKGROUND: The implementation of the multidisciplinary team conference has been shown to improve treatment outcome for patients with gastric- and gastroesophageal cancer. Likewise, the staging laparoscopy has increased the detection of patients with disseminated disease, that is, patients who do not benefit from a surgical resection. The aim of this study was to compare the multidisciplinary team conference's decision in respect of M-staging with the findings of the following staging laparoscopy. METHODS: Patients considered operable and resectable within the multidisciplinary team conference in the period 2010-2012 were retrospectively reviewed. Patient data were retrieved by searching for specific diagnosis and operation codes in the in-house system. The inclusion criteria were as follows: biopsy-verified cancer of the esophagus, gastroesophageal junction or stomach, and no suspicion of peritoneal carcinomatosis or liver metastases on multidisciplinary team conference before staging laparoscopy. Furthermore, an evaluation with staging laparoscopy was required. RESULTS: In total, 222 patients met the inclusion criteria. Most cancers were located in the gastroesophageal junction, n = 171 (77.0%), and most common with adenocarcinoma histology, n = 196 (88.3%). The staging laparoscopy was M1-positive for peritoneal carcinomatosis in eight patients (16.7%) with gastric cancer versus nine patients (5.3%) with gastroesophageal junction cancer. Furthermore, liver metastases were evident in zero patients (0.0%) and four patients (2.3%) with gastric- and gastroesophageal junction cancer, respectively. The staging laparoscopy findings regarding peritoneal carcinomatosis were significantly different between gastric- and gastroesophageal junction cancers, p = 0.01. No significant differences were found regarding T-/N-stage or histological tumor characteristics between the positive- and negative-staging laparoscopy group. CONCLUSION: The M-staging of the multidisciplinary team conference without staging laparoscopy lacks accuracy concerning peritoneal carcinomatosis. Staging laparoscopy remains an essential part of the preoperative detection of disseminated disease in patients with gastric- and gastroesophageal cancer. PMID- 26261201 TI - PTX3-Based Genetic Testing for Risk of Aspergillosis After Lung Transplant. PMID- 26261202 TI - Reply to Messori. PMID- 26261203 TI - Brucellosis in Iran: Why Not Eradicated? PMID- 26261204 TI - Newest Treatments for Hepatitis C: How Can We Manage Sustainability? PMID- 26261205 TI - The Use of Ebola Convalescent Plasma to Treat Ebola Virus Disease in Resource Constrained Settings: A Perspective From the Field. AB - The clinical evaluation of convalescent plasma (CP) for the treatment of Ebola virus disease (EVD) in the current outbreak, predominantly affecting Guinea, Sierra Leone, and Liberia, was prioritized by the World Health Organization in September 2014. In each of these countries, nonrandomized comparative clinical trials were initiated. The Ebola-Tx trial in Conakry, Guinea, enrolled 102 patients by 7 July 2015; no severe adverse reactions were noted. The Ebola-CP trial in Sierra Leone and the EVD001 trial in Liberia have included few patients. Although no efficacy data are available yet, current field experience supports the safety, acceptability, and feasibility of CP as EVD treatment. Longer-term follow-up as well as data from nontrial settings and evidence on the scalability of the intervention are required. CP sourced from within the outbreak is the most readily available source of anti-EVD antibodies. Until the advent of effective antivirals or monoclonal antibodies, CP merits further evaluation. PMID- 26261207 TI - Antifungal Prophylaxis in Liver Transplant Recipients. PMID- 26261206 TI - Reply to Cunha et al. PMID- 26261208 TI - Reply to Winston et al. PMID- 26261209 TI - TDP-43 affects splicing profiles and isoform production of genes involved in the apoptotic and mitotic cellular pathways. AB - In recent times, high-throughput screening analyses have broadly defined the RNA cellular targets of TDP-43, a nuclear factor involved in neurodegeneration. A common outcome of all these studies is that changing the expression levels of this protein can alter the expression of several hundred RNAs within cells. What still remains to be clarified is which changes represent direct cellular targets of TDP-43 or just secondary variations due to the general role played by this protein in RNA metabolism. Using an HTS-based splicing junction analysis we identified at least six bona fide splicing events that are consistent with being controlled by TDP-43. Validation of the data, both in neuronal and non-neuronal cell lines demonstrated that TDP-43 substantially alters the levels of isoform expression in four genes potentially important for neuropathology: MADD/IG20, STAG2, FNIP1 and BRD8. For MADD/IG20 and STAG2, these changes could also be confirmed at the protein level. These alterations were also observed in a cellular model that successfully mimics TDP-43 loss of function effects following its aggregation. Most importantly, our study demonstrates that cell cycle alterations induced by TDP-43 knockdown can be recovered by restoring the STAG2, an important component of the cohesin complex, normal splicing profile. PMID- 26261210 TI - TRAP150 interacts with the RNA-binding domain of PSF and antagonizes splicing of numerous PSF-target genes in T cells. AB - PSF (a.k.a. SFPQ) is a ubiquitously expressed, essential nuclear protein with important roles in DNA damage repair and RNA biogenesis. In stimulated T cells, PSF binds to and suppresses the inclusion of CD45 exon 4 in the final mRNA; however, in resting cells, TRAP150 binds PSF and prevents access to the CD45 RNA, though the mechanism for this inhibition has remained unclear. Here, we show that TRAP150 binds a region encompassing the RNA recognition motifs (RRMs) of PSF using a previously uncharacterized, 70 residue region we have termed the PSF interacting domain (PID). TRAP150's PID directly inhibits the interaction of PSF RRMs with RNA, which is mediated through RRM2. However, interaction of PSF with TRAP150 does not appear to inhibit the dimerization of PSF with other Drosophila Behavior, Human Splicing (DBHS) proteins, which is also dependent on RRM2. Finally, we use RASL-Seq to identify ~40 T cell splicing events sensitive to PSF knockdown, and show that for the majority of these, PSF's effect is antagonized by TRAP150. Together these data suggest a model in which TRAP150 interacts with dimeric PSF to block access of RNA to RRM2, thereby regulating the activity of PSF toward a broad set of splicing events in T cells. PMID- 26261211 TI - Widespread alternative and aberrant splicing revealed by lariat sequencing. AB - Alternative splicing is an important and ancient feature of eukaryotic gene structure, the existence of which has likely facilitated eukaryotic proteome expansions. Here, we have used intron lariat sequencing to generate a comprehensive profile of splicing events in Schizosaccharomyces pombe, amongst the simplest organisms that possess mammalian-like splice site degeneracy. We reveal an unprecedented level of alternative splicing, including alternative splice site selection for over half of all annotated introns, hundreds of novel exon-skipping events, and thousands of novel introns. Moreover, the frequency of these events is far higher than previous estimates, with alternative splice sites on average activated at ~3% the rate of canonical sites. Although a subset of alternative sites are conserved in related species, implying functional potential, the majority are not detectably conserved. Interestingly, the rate of aberrant splicing is inversely related to expression level, with lowly expressed genes more prone to erroneous splicing. Although we validate many events with RNAseq, the proportion of alternative splicing discovered with lariat sequencing is far greater, a difference we attribute to preferential decay of aberrantly spliced transcripts. Together, these data suggest the spliceosome possesses far lower fidelity than previously appreciated, highlighting the potential contributions of alternative splicing in generating novel gene structures. PMID- 26261212 TI - hSSB1 (NABP2/ OBFC2B) is required for the repair of 8-oxo-guanine by the hOGG1 mediated base excision repair pathway. AB - The maintenance of genome stability is essential to prevent loss of genetic information and the development of diseases such as cancer. One of the most common forms of damage to the genetic code is the oxidation of DNA by reactive oxygen species (ROS), of which 8-oxo-7,8-dihydro-guanine (8-oxoG) is the most frequent modification. Previous studies have established that human single stranded DNA-binding protein 1 (hSSB1) is essential for the repair of double stranded DNA breaks by the process of homologous recombination. Here we show that hSSB1 is also required following oxidative damage. Cells lacking hSSB1 are sensitive to oxidizing agents, have deficient ATM and p53 activation and cannot effectively repair 8-oxoGs. Furthermore, we demonstrate that hSSB1 forms a complex with the human oxo-guanine glycosylase 1 (hOGG1) and is important for hOGG1 localization to the damaged chromatin. In vitro, hSSB1 binds directly to DNA containing 8-oxoguanines and enhances hOGG1 activity. These results underpin the crucial role hSSB1 plays as a guardian of the genome. PMID- 26261213 TI - Paradoxical suppression of small RNA activity at high Hfq concentrations due to random-order binding. AB - Small RNAs (sRNAs) are important regulators of gene expression during bacterial stress and pathogenesis. sRNAs act by forming duplexes with mRNAs to alter their translation and degradation. In some bacteria, duplex formation is mediated by the Hfq protein, which can bind the sRNA and mRNA in each pair in a random order. Here we investigate the consequences of this random-order binding and experimentally demonstrate that it can counterintuitively cause high Hfq concentrations to suppress rather than promote sRNA activity in Escherichia coli. As a result, maximum sRNA activity occurs when the Hfq concentration is neither too low nor too high relative to the sRNA and mRNA concentrations ('Hfq set point'). We further show with models and experiments that random-order binding combined with the formation of a dead-end mRNA-Hfq complex causes high concentrations of an mRNA to inhibit its own duplex formation by sequestering Hfq. In such cases, maximum sRNA activity requires an optimal mRNA concentration ('mRNA set-point') as well as an optimal Hfq concentration. The Hfq and mRNA set points generate novel regulatory properties that can be harnessed by native and synthetic gene circuits to provide greater control over sRNA activity, generate non-monotonic responses and enhance the robustness of expression. PMID- 26261214 TI - Molecular basis of ribosome recognition and mRNA hydrolysis by the E. coli YafQ toxin. AB - Bacterial type II toxin-antitoxin modules are protein-protein complexes whose functions are finely tuned by rapidly changing environmental conditions. E. coli toxin YafQ is suppressed under steady state growth conditions by virtue of its interaction with its cognate antitoxin, DinJ. During stress, DinJ is proteolytically degraded and free YafQ halts translation by degrading ribosome bound mRNA to slow growth until the stress has passed. Although structures of the ribosome with toxins RelE and YoeB have been solved, it is unclear what residues among ribosome-dependent toxins are essential for mediating both recognition of the ribosome and the mRNA substrate given their low sequence identities. Here we show that YafQ coordinates binding to the 70S ribosome via three surface-exposed patches of basic residues that we propose directly interact with 16S rRNA. We demonstrate that YafQ residues H50, H63, D67 and H87 participate in acid-base catalysis during mRNA hydrolysis and further show that H50 and H63 functionally complement as general bases to initiate the phosphodiester cleavage reaction. Moreover YafQ residue F91 likely plays an important role in mRNA positioning. In summary, our findings demonstrate the plasticity of ribosome-dependent toxin active site residues and further our understanding of which toxin residues are important for function. PMID- 26261215 TI - Integrated analysis of numerous heterogeneous gene expression profiles for detecting robust disease-specific biomarkers and proposing drug targets. AB - Genome-wide expression profiling has revolutionized biomedical research; vast amounts of expression data from numerous studies of many diseases are now available. Making the best use of this resource in order to better understand disease processes and treatment remains an open challenge. In particular, disease biomarkers detected in case-control studies suffer from low reliability and are only weakly reproducible. Here, we present a systematic integrative analysis methodology to overcome these shortcomings. We assembled and manually curated more than 14,000 expression profiles spanning 48 diseases and 18 expression platforms. We show that when studying a particular disease, judicious utilization of profiles from other diseases and information on disease hierarchy improves classification quality, avoids overoptimistic evaluation of that quality, and enhances disease-specific biomarker discovery. This approach yielded specific biomarkers for 24 of the analyzed diseases. We demonstrate how to combine these biomarkers with large-scale interaction, mutation and drug target data, forming a highly valuable disease summary that suggests novel directions in disease understanding and drug repurposing. Our analysis also estimates the number of samples required to reach a desired level of biomarker stability. This methodology can greatly improve the exploitation of the mountain of expression profiles for better disease analysis. PMID- 26261217 TI - How does joint procurement affect the design, customisation and usability of a hospital ePrescribing system? AB - The aim of this article is to explore the effect of the joint procurement model adopted during the English National Programme for Information Technology (NPfIT) on the customisation, design and usability of a hospital ePrescribing system. Drawing on qualitative data collected at two case study sites deploying an ePrescribing system jointly procured within one of the NPfIT's geographical clusters, we explain how procurement decisions, difficult relationships with the supplier and strict contractual arrangements contributed to usability issues and difficulties in the customisation process. While some limited change requests made by users were taken up by the developers, these were seen by users as insufficient to meet local clinical needs and practices. A joint procurement approach, such as the NPfIT, thus limited the opportunity and scope of the changes to the ePrescribing system, which impinged not only on the perceived success of the implementation but also on the system's usability. PMID- 26261216 TI - Towards a shared service centre for telemedicine: Telemedicine in Denmark, and a possible way forward. AB - : Although evidence of the effectiveness of telemedicine is accumulating, knowledge of how to make best use of telemedicine is limited. This article presents results from a multi-stakeholder project that developed a new concept, a 'shared service centre' for telemedicine that is envisioned as working across different telemedical initiatives to support the implementation and wider adoption of telemedicine. One year of participatory design and analysis of the shared service centre concept involved stakeholders, such as clinicians, patients, technicians, policy makers, lawyers, economists and information technology architects. More than 100 people contributed to the findings. Most of the ideas generated for potential centre support for telemedicine could be categorised under four service categories. The need for such support services was verified in the cases investigated, and by agreement among stakeholders from regional health authorities, municipalities, and general practice. Therefore, it is probable that a shared service centre could help enable the wider deployment of telemedicine. DEFINITIONS: In this article, we use 'telemedicine' as an umbrella term for all the 'tele-' labels that are sometimes used rather indiscriminately to denote the use of information and technology to support healthcare services, including 'telehealth', 'telemonitoring', 'telehomecare', 'e health', and so on. As per our definition, telemedicine may be synchronous and/or asynchronous, and may apply to any information and technology-based means of connecting healthcare actors and the patient, such as video communication, e mail, electronic monitoring equipment, and Internet portals. Furthermore, the term 'telemedical initiative' covers projects in which telemedicine is conducted by a temporary project organisation, as well as self-contained telemedicine services used in daily, clinical practice in existing organisations. PMID- 26261218 TI - Predictors of online health information seeking behavior: Changes between 2002 and 2012. AB - The Internet has become an important and preferred source of health information. Although the literature has highlighted several key predictors that influence an individual's online health information seeking behavior, insufficient attention has been paid to the changes in the predictors' roles and effects over time. This study explores and compares the effects that specific predictors had on online health information seeking behavior over a period of 10 years by integrating and analyzing two Pew datasets collected in 2002 and 2012. Hierarchical regression analyses indicate that socio-demographic factors and overall health condition are significant predictors that had an increasing impact on online health information seeking behavior. However, the impact of Internet usage decreased significantly from 2002 to 2012. A comparison across time contributes to a vertical understanding of the changes in online health information seeking behavior and its predictors and helps health professionals and researchers tailor their informational interventions to meet the up-to-date needs and preferences of users. PMID- 26261219 TI - Ethnic origin and access to electronic health services. AB - E-health holds the promise of changing the delivery of health care by extending and enhancing its reach, and democratizing and improving the access of disadvantaged groups to health care services. This study investigated ethnic inequalities in access to e-health information, communication and electronic services in Israel. Based on the diversification hypothesis, we expected that disadvantaged ethnic groups would be more likely to use e-health services to compensate for their lack of social capital. Data gathered from a representative sample of Internet users in Israel (n=1371) provided partial support for the hypothesis, indicating that in multicultural societies, disadvantaged groups are more motivated than the majority group to use the Internet to access medical information. However, despite expectations, minority groups were less likely to access e-health services. Implications of the findings are discussed. PMID- 26261220 TI - Supporting Active Patient and Health Care Collaboration: A Prototype for Future Health Care Information Systems. AB - This article presents and illustrates the main features of a proposed process oriented approach for patient information distribution in future health care information systems, by using a prototype of a process support system. The development of the prototype was based on the Visuera method, which includes five defined steps. The results indicate that a visualized prototype is a suitable tool for illustrating both the opportunities and constraints of future ideas and solutions in e-Health. The main challenges for developing and implementing a fully functional process support system concern both technical and organizational/management aspects. PMID- 26261222 TI - GMcloser: closing gaps in assemblies accurately with a likelihood-based selection of contig or long-read alignments. AB - MOTIVATION: Genome assemblies generated with next-generation sequencing (NGS) reads usually contain a number of gaps. Several tools have recently been developed to close the gaps in these assemblies with NGS reads. Although these gap-closing tools efficiently close the gaps, they entail a high rate of misassembly at gap-closing sites. RESULTS: We have found that the assembly error rates caused by these tools are 20-500-fold higher than the rate of errors introduced into contigs by de novo assemblers. We here describe GMcloser, a tool that accurately closes these gaps with a preassembled contig set or a long read set (i.e., error-corrected PacBio reads). GMcloser uses likelihood-based classifiers calculated from the alignment statistics between scaffolds, contigs and paired-end reads to correctly assign contigs or long reads to gap regions of scaffolds, thereby achieving accurate and efficient gap closure. We demonstrate with sequencing data from various organisms that the gap-closing accuracy of GMcloser is 3-100-fold higher than those of other available tools, with similar efficiency. AVAILABILITY AND IMPLEMENTATION: GMcloser and an accompanying tool (GMvalue) for evaluating the assembly and correcting misassemblies except SNPs and short indels in the assembly are available at https://sourceforge.net/projects/gmcloser/. CONTACT: shunichi.kosugi@riken.jp. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26261221 TI - Rates and risks for late referral to hospice in patients with primary malignant brain tumors. AB - BACKGROUND: Primary malignant brain tumors (PMBTs) are devastating malignancies with poor prognosis. Optimizing psychosocial and supportive care is critical, especially in the later stages of disease. METHODS: This retrospective cohort study compared early versus late hospice enrollment of PMBT patients admitted to the home hospice program of a large urban, not-for-profit home health care agency between 2009 and 2013. RESULTS: Of 160 patients with PMBT followed to death in hospice care, 32 (22.5%) were enrolled within 7 days of death. When compared with patients referred to hospice more than 7 days before death, a greater proportion of those with late referral were bedbound at admission (97.2% vs 61.3%; OR=21.85; 95% CI, 3.42-919.20; P < .001), aphasic (61.1% vs 20.2%; OR = 6.13; 95% CI, 2.59 15.02; P < .001), unresponsive (38.9% vs 4%; OR = 14.76,;95% CI, 4.47-57.98; P < .001), or dyspneic (27.8% vs 9.7%; OR = 21.85; 95% CI, 3.42-10.12; P = .011). In multivariable analysis, male patients who were receiving Medicaid or charitable care and were without a health care proxy were more likely to enroll in hospice within 1 week of death. CONCLUSIONS: Late hospice referral in PMBT is common. PMBT patients enrolled late in hospice are severely neurologically debilitated at the time hospice is initiated and therefore may not derive optimal benefit from multidisciplinary hospice care. Men, patients with lower socioeconomic status, and those without a health care proxy may be at risk for late hospice care and may benefit from proactive discussion about end-of-life care in PMBT, but prospective studies are needed. PMID- 26261223 TI - Vizardous: interactive analysis of microbial populations with single cell resolution. AB - MOTIVATION: Single cell time-lapse microscopy is a powerful method for investigating heterogeneous cell behavior. Advances in microfluidic lab-on-a-chip technologies and live-cell imaging render the parallel observation of the development of individual cells in hundreds of populations possible. While image analysis tools are available for cell detection and tracking, biologists are still confronted with the challenge of exploring and evaluating this data. RESULTS: We present the software tool Vizardous that assists scientists with explorative analysis and interpretation tasks of single cell data in an interactive, configurable and visual way. With Vizardous, lineage tree drawings can be augmented with various, time-resolved cellular characteristics. Associated statistical moments bridge the gap between single cell and the population-average level. AVAILABILITY AND IMPLEMENTATION: The software, including documentation and examples, is available as executable Java archive as well as in source form at https://github.com/modsim/vizardous. CONTACT: k.noeh@fz-juelich.de. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26261224 TI - SuccFind: a novel succinylation sites online prediction tool via enhanced characteristic strategy. AB - Lysine succinylation orchestrates a variety of biological processes. Annotation of succinylation in proteomes is the first-crucial step to decipher physiological roles of succinylation implicated in the pathological processes. In this work, we developed a novel succinylation site online prediction tool, called SuccFind, which is constructed to predict the lysine succinylation sites based on two major categories of characteristics: sequence-derived features and evolutionary-derived information of sequence and via an enhanced feature strategy for further optimizations. The assessment results obtained from cross-validation suggest that SuccFind can provide more instructive guidance for further experimental investigation of protein succinylation. AVAILABILITY AND IMPLEMENTATION: A user friendly server is freely available on the web at: http://bioinfo.ncu.edu.cn/SuccFind.aspx. CONTACT: jdqiu@ncu.edu.cn. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26261225 TI - Streptococcal Diversity of Human Milk and Comparison of Different Methods for the Taxonomic Identification of Streptococci. AB - BACKGROUND: The genus Streptococcus is 1 of the dominant bacterial groups in human milk, but the taxonomic identification of some species remains difficult. OBJECTIVE: The objective of this study was to investigate the discriminatory ability of different methods to identify streptococcal species in order to perform an assessment of the streptococcal diversity of human milk microbiota as accurately as possible. METHODS: The identification of 105 streptococcal strains from human milk was performed by 16S rRNA, tuf, and sodA gene sequencing, phylogenetic analysis, and Matrix Assisted Laser Desorption Ionization-Time of Flight (MALDI-TOF) mass spectrometry. RESULTS: Streptococcus salivarius, Streptococcus mitis, and Streptococcus parasanguinis were the streptococcal dominant species in the human milk microbiota. Sequencing of housekeeping genes allowed the classification of 96.2% (16S rRNA), 84.8% ( sodA), and 88.6% ( tuf) of the isolates. Phylogenetic analysis showed 3 main streptococcal clusters corresponding with the mitis (73 isolates), salivarius (29), mutans (1)-pyogenic (2) groups, but many of the mitis group isolates (36) could not be assigned to any species. The application of the MALDI-TOF Bruker Biotyper system resulted in the identification of 56 isolates (53.33%) at the species level, but it could not discriminate between S pneumoniae and S mitis isolates, in contrast to the Vitek MS system. CONCLUSION: There was a good agreement among the different methods assessed in this study to identify those isolates of the salivarius, mutans, and pyogenic groups, whereas unambiguous discrimination could not be achieved concerning some species of the mitis group ( S mitis, S pneumoniae, S pseudopneumoniae, S oralis). PMID- 26261226 TI - An Evaluation of the CDC's Community-Based Breastfeeding Supplemental Cooperative Agreement: Reach, Strategies, Barriers, Facilitators, and Lessons Learned. AB - BACKGROUND: Community-based organizations (CBOs) have an important role to play in promoting breastfeeding continuation among mothers. The Centers for Disease Control and Prevention's Nutrition, Physical Activity, and Obesity Program's Cooperative Agreement Breastfeeding Supplement funded 6 state health departments to support CBOs to implement community-based breastfeeding support activities. OBJECTIVES: Study objectives were to (1) describe the reach of the Cooperative Agreement, (2) describe breastfeeding support strategies implemented by state health departments and CBOs, and (3) understand the barriers and facilitators to implementing community-based breastfeeding support strategies. METHODS: Qualitative and quantitative data were abstracted from state health departments' final evaluation reports. Qualitative data were analyzed for common themes using deductive and inductive approaches. RESULTS: Within the 6 states funded by the Cooperative Agreement, 66 primary CBOs implemented breastfeeding support strategies and reported 59 256 contacts with mothers. Support strategies included incorporating lactation services into community-based programs, training staff, providing walk-in locations for lactation support, connecting breastfeeding mothers to resources, and providing services that reflect community-specific culture. Community partnerships, network building, stakeholders' commitment, and programmatic and policy environments were key facilitators of program success. CONCLUSION: Key lessons learned include the importance of time in creating lasting organizational change, use of data for program improvement, choosing the right partners, taking a collective approach, and leveraging resources. PMID- 26261227 TI - Ischaemia-reperfusion injury masquerading as an infected finger in a 12 month old. PMID- 26261228 TI - Change in the collateral and accessory collateral ligament lengths of the proximal interphalangeal joint using cadaveric model three-dimensional laser scanning. AB - The purpose of this study was to assess the lengths of the index and middle finger proximal interphalangeal joint ligaments and determine the relative changes in the collateral and accessory collateral ligament lengths at 0 degrees , 45 degrees and 90 degrees flexion. We generated three-dimensional scans of 16 finger (eight index and eight middle) proximal interphalangeal joints to assess relative changes in ligament length. Significant changes were found between 45 degrees -90 degrees and 0 degrees -90 degrees for the ulnar collateral ligament of the index finger and both collateral ligaments of the middle finger between 45 degrees -90 degrees and 0 degrees -90 degrees . No significant changes in length were found for the radial collateral ligament of the index finger or the accessory collateral ligaments of the index and middle fingers. Overall, it was found that the collateral ligament length changed significantly, but there was no significant change in the accessory collateral ligaments. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 26261229 TI - Prevalence of amblyopia and strabismus in Eastern China: results from screening of preschool children aged 36-72 months. AB - PURPOSE: To determine the prevalence of amblyopia and strabismus in preschool children in Eastern China. METHODS: The Nanjing Pediatric Vision Project was a cross-sectional, population-based cohort study conducted in preschool children aged 36-72 months from 2011 to 2012 in Yuhua District, Nanjing, China, using an age-stratified random sampling procedure. A questionnaire totalling 117 items was sent to be completed by the corresponding parents or legal guardians of each eligible child. Comprehensive eye examinations, including visual acuity, anterior segment examination, autorefraction, cover test and ocular motility, were conducted. Postcycloplegic refraction and fundus examinations were performed if necessary. RESULTS: Amblyopia was present in 68 children (1.20%, 95% CI 0.92% to 1.48%), with no statistical differences in gender (p=0.903) and age (p=0.835). Among these, 27 had bilateral amblyopia and 41 had unilateral amblyopia, including 26 anisometropic without strabismus, 26 binocular refractive, 7 strabismic, 6 combined strabismic/anisometropic and 3 deprivation amblyopia. Strabismus was found in 320 children (5.65%, 95% CI 5.05% to 6.25%), including 43 with concomitant esotropia, 259 with concomitant exotropia (1 esotropia at near but exotropia at distance), 8 with microtropia (3 esotropia and 5 exotropia), 10 with pure vertical strabismus (3 dissociated vertical deviation and 7 oblique muscle dysfunction) and 1 with Type I Duane syndrome. The prevalence of strabismus had no statistical differences in gender (p=0.952), but had significant statistical differences between different age groups (p=0.021). CONCLUSIONS: The prevalence of amblyopia and strabismus in preschool children in Eastern China were 1.20% and 5.65%, respectively. The refractive and strabismus are the main factors associated with amblyopia. PMID- 26261230 TI - Choroidal thickening prior to anterior recurrence in patients with Vogt-Koyanagi Harada disease. AB - AIM: To assess choroidal thickness changes associated with anterior segment recurrences in patients with Vogt-Koyanagi-Harada (VKH) disease using enhanced depth imaging optical coherence tomography (EDI-OCT). METHODS: EDI-OCT images were obtained periodically from 11 patients with VKH disease (22 eyes) who were followed-up due to anterior segment recurrences. Subfoveal choroidal thickness (SCT) values at the following stages were evaluated: (1) during the remission phase, (2) 1 month before detecting the anterior recurrence, (3) during the anterior recurrence and (4) after systemic prednisolone (PSL) treatment leading to remission. In comparison with SCT values in remission as baseline, the changing ratios of SCT were statistically analysed at subsequent three stages. RESULTS: The average of the SCT changing ratios compared with the remission phase significantly increased to 1.45+/-0.11 during anterior segment recurrences (p=0.00044) lacking any funduscopic signs of posterior involvement. Interestingly, the average SCT ratio 1 month before detecting the recurrence had already increased to 1.30+/-0.08 (p=0.002). After the PSL treatment, the ratio of SCT recovered to 0.95+/-0.03, which was equivalent to the remission level. However, in patients with their remission SCT values less than 240 um, the SCT ratio did not increase significantly at any time points evaluated. CONCLUSIONS: The choroid in eyes with VKH disease thickened in association with the anterior segment recurrence, and this thickening was observed prior to the recurrence. EDI OCT may be useful for detecting latent choroidal inflammation in VKH disease, whereas it may not for patients with the relatively thin choroid. TRIAL REGISTRATION NUMBER: The trial registration number of the internal review board of Hokkaido University Hospital is 014-0384. PMID- 26261232 TI - Radial versus raster spectral-domain optical coherence tomography scan patterns for detection of macular fluid in neovascular age-related macular degeneration. AB - BACKGROUND/AIMS: To compare the 12-line radial to the 25-line raster spectral domain optical coherence tomography (SD-OCT) acquisition patterns at detecting intraretinal or subretinal fluid in eyes with neovascular age-related macular degeneration (AMD). METHODS: Retrospective cross-sectional analysis of 200 eyes with neovascular AMD. Sequential 12-line radial and 25-line raster scans were evaluated for the presence of intraretinal/subretinal fluid. RESULTS: A total of 394 SD-OCT scans were interpreted (1.97 scans per eye). The 12-line radial detected intraretinal/subretinal fluid in all but 7 of 394 scans (1.7%; 95% CI 0.7% to 3.6%), resulting in a sensitivity of 98.3%. The 25-line raster detected intraretinal/subretinal fluid in all but 10 of 394 scans (2.5%; 95% CI 1.2% to 4.6%), resulting in a sensitivity of 97.5%. This small difference in fluid detection between the two acquisition patterns for neovascular AMD was not found to be statistically significant (p=0.6276). CONCLUSIONS: The 12-line radial scan is statistically comparable with the 25-line raster scan in detecting the presence of intraretinal/subretinal fluid in neovascular AMD. The 12-line radial SD-OCT pattern alone may be adequate to guide day-to-day clinical decisions in a more time-efficient manner. PMID- 26261231 TI - Analysis of human cytomegalovirus replication in primary cultured human corneal endothelial cells. AB - BACKGROUND/AIMS: Since the first case of human cytomegalovirus (HCMV)-induced corneal endotheliitis in which HCMV DNA was detected from the patient's aqueous humour using PCR, the clinical evidence for HCMV endotheliitis has been accumulating. However, it remains to be confirmed whether HCMV can efficiently replicate in corneal endothelial cells. We, therefore, sought to determine whether primary cultured human corneal endothelial cells (HCECs) could support HCMV replication. METHODS: Human foreskin fibroblasts (HFFs) have been shown to be fully permissive for HCMV replication, and are commonly used as an in vitro model for HCMV lytic replication. Therefore, primary cultured HCECs or HFFs were infected with the vascular endotheliotropic HCMV strain TB40/E or laboratory strain Towne. We then compared viral mRNA and protein expression, genome replication and growth between the TB40/E-infected and Towne-infected HCECs and HFFs. RESULTS: When HCECs were infected with TB40/E or Towne, rounded cells resembling owl's eyes as well as viral antigens were detected. Viral mRNA synthesis and protein expression proceeded efficiently in the HCECs and HFFs infected with TB40/E or Towne at a high multiplicity of infection (MOI). Similarly, the viral genome was also effectively replicated, with UL44--a viral DNA polymerase processivity factor--foci observed in the nuclei of HCECs. HCECs produced a substantial number of infectious virions after infection with TB40/E at both a high and low MOI. CONCLUSIONS: Primary cultured HCECs could efficiently support HCMV replication after infection at both a high and low MOI. PMID- 26261233 TI - A Path Model of School Violence Perpetration: Introducing Online Game Addiction as a New Risk Factor. AB - Drawing on the cognitive information-processing model of aggression and the general aggression model, we explored why adolescents become addicted to online games and how their immersion in online games affects school violence perpetration (SVP). For this purpose, we conducted statistical analyses on 1,775 elementary and middle school students who resided in northern districts of Seoul, South Korea. The results validated the proposed structural equation model and confirmed the statistical significance of the structural paths from the variables; that is, the paths from child abuse and self-esteem to SVP were significant. The levels of self-esteem and child abuse victimization affected SVP, and this effect was mediated by online game addiction (OGA). Furthermore, a multigroup path analysis showed significant gender differences in the path coefficients of the proposed model, indicating that gender exerted differential effects on adolescents' OGA and SVP. Based on these results, prevention and intervention methods to curb violence in schools have been proposed. PMID- 26261234 TI - Overcoming Abuse: A Phenomenological Investigation of the Journey to Recovery From Past Intimate Partner Violence. AB - To date, minimal research has focused on the recovery process for survivors of intimate partner violence (IPV). This study utilized a phenomenological methodology to understand the lived experiences of survivors of IPV ( N = 123) who had overcome abusive relationships and created violence-free and meaningful lives. The researchers aimed to understand key factors involved in their recovery processes. Results indicated two main processes in the IPV recovery process: intrapersonal processes and interpersonal processes. Intrapersonal processes included (a) regaining and recreating one's identity, (b) embracing the freedom and power to direct one's own life, (c) healing from the mental and physical health symptoms of the abuse, (d) fostering acceptance and forgiveness with self and abuser, (e) education and examination of abusive relationships, (f) determining whether and how to enter new intimate relationships, and (g) acknowledging the long-term process of overcoming abuse. Interpersonal processes included themes of (a) building positive social support and relationships and (b) using ones' experiences with abuse to help others. Results of the present study are presented, and implications for practitioners are discussed. PMID- 26261235 TI - Correction of coronal alignment correlates with reconstruction of joint height in unicompartmental knee arthroplasty. AB - OBJECTIVES: Because there have been no standard methods to determine pre operatively the thickness of resection of the proximal tibia in unicompartmental knee arthroplasty (UKA), information about the relationship between the change of limb alignment and the joint line elevation would be useful for pre-operative planning. The purpose of this study was to clarify the correlation between the change of limb alignment and the change of joint line height at the medial compartment after UKA. METHODS: A consecutive series of 42 medial UKAs was reviewed retrospectively. These patients were assessed radiographically both pre- and post-operatively with standing anteroposterior radiographs. The thickness of bone resection at the proximal tibia and the distal femur was measured radiographically. The relationship between the change of femorotibial angle (deltaFTA) and the change of joint line height, was analysed. RESULTS: The mean pre- and post-operative FTA was 180.5 degrees (172.2 degrees to 184.8 degrees ) and 175.0 degrees (168.5 degrees to 178.9 degrees ), respectively. The mean deltaFTA was 5.5 degrees (2.3 degrees to 10.1 degrees ). The joint line elevation of the tibia (JLET) was 4.4 mm (2.1 to 7.8). The deltaFTA was correlated with the JLET (correlation coefficient 0.494, p = 0.0009). CONCLUSIONS: This study indicated that there is a significant correlation between the change of limb alignment and joint line elevation. This observation suggests that it is possible to know the requirement of elevation of the joint line to obtain the desired correction of limb alignment, and to predict the requirement of bone resection of the proximal tibia pre-operatively. Cite this article: Bone Joint Res 2015;4:128-133. PMID- 26261236 TI - Options for reducing oil content of sludge from a petroleum wastewater treatment plant. AB - Wastewater treatment plants at petroleum refineries often produce substantial quantities of sludge with relatively high concentrations of oil. Disposal of this waste is costly, in part because the high oil content requires use of secure disposal methods akin to handling of hazardous wastes. This article examines the properties of oily sludge and evaluates optional methods for reducing the oil content of this sludge to enable use of lower cost disposal methods. To reduce the oil content or break the structure of oily sludge, preliminary lab-scale experiments involving mechanical treatment, surfactant extraction, and oxidation are conducted. By applying surfactants, approximately 36% to 45% of oils are extracted from oily sludge. Of this, about 33% of oils are rapidly oxidised via radiation by an electron beam within 10 s of exposure. The Fenton reaction is effective for destruction of oily sludge. It is also found that 56% of oils were removed by reacting oily sludge with water containing ozone of 0.5 mg l(-1) over a period of 24 h. Oxidation using ozone thus can also be effectively used as a pretreatment for oily sludge. PMID- 26261237 TI - E-cigarette use and willingness to smoke: a sample of adolescent non-smokers. AB - OBJECTIVE: There is little evidence on the consequences of using electronic cigarettes (e-cigarette) in adolescence. With a multiethnic sample of non smokers, we assessed the relation between e-cigarette use and social-cognitive factors that predict smoking of combustible cigarettes. METHODS: School-based cross-sectional survey of 2309 high school students (mean age 14.7 years). Participants reported on e-cigarette use and cigarette use; on smoking-related cognitions (smoking expectancies, prototypes of smokers) and peer smoker affiliations; and on willingness to smoke cigarettes. Regression analyses conducted for non-cigarette smokers tested the association between e-cigarette use and willingness to smoke cigarettes, controlling for demographics, parenting, academic and social competence, and personality variables. Structural equation modelling (SEM) analysis tested whether the relation between e-cigarette use and willingness to smoke was mediated through any of the three smoking-related variables. RESULTS: Non-smokers who had used e-cigarettes (18% of the total sample) showed more willingness to smoke cigarettes compared with those who had never used any tobacco product; the adjusted OR was 2.35 (95% CI 1.73 to 3.19). SEM showed that the relation between e-cigarette use and willingness to smoke was partly mediated through more positive expectancies about smoking, but there was also a direct path from e-cigarette use to willingness. CONCLUSIONS: Among adolescent non-smokers, e-cigarette use is associated with willingness to smoke, a predictor of future cigarette smoking. The results suggest that use of e cigarettes by adolescents is not without attitudinal risk for cigarette smoking. These findings have implications for formulation of policy about access to e cigarettes by adolescents. PMID- 26261238 TI - Ropeginterferon alfa-2b, a novel IFNalpha-2b, induces high response rates with low toxicity in patients with polycythemia vera. AB - In this prospective, open-label, multicenter phase 1/2 dose escalation study, we used a next-generation, mono-pegylated interferon (IFN) alpha-2b isoform, ropeginterferon alfa-2b. The unique feature of ropeginterferon alfa-2b is a longer elimination half-life, which allows administration every 2 weeks. We present data from 51 polycythemia vera patients. The main goal was to define the maximum tolerated dose and to assess safety and efficacy. A dose range of 50 to 540 ug was tested without the appearance of dose-limiting toxicities. All drug related adverse events were known toxicities associated with IFN-alpha. The cumulative overall response rate was 90%, comprising complete response in 47% and partial response in 43% of patients; the best individual molecular response level was a complete response in 21% of patients and partial response in 47%. Notably, we did not observe any correlation between the dose level and the response rate or response duration, suggesting that already low levels of ropeginterferon alfa 2b are sufficient to induce significant hematologic and molecular responses. These data suggest promising efficacy and safety of ropeginterferon alfa-2b and support the development of the drug in a randomized phase 3 clinical trial. The study was disclosed at www.clinicaltrials.gov as #NCT01193699 before including the first patient. PMID- 26261240 TI - SUMOylation-disrupting WAS mutation converts WASp from a transcriptional activator to a repressor of NF-kappaB response genes in T cells. AB - In Wiskott-Aldrich syndrome (WAS), immunodeficiency and autoimmunity often comanifest, yet how WAS mutations misregulate chromatin-signaling in Thelper (TH) cells favoring development of auto-inflammation over protective immunity is unclear. Previously, we identified an essential promoter-specific, coactivator role of nuclear-WASp in TH1 gene transcription. Here we identify small ubiquitin related modifier (SUMO)ylation as a novel posttranslational modification of WASp, impairment of which converts nuclear-WASp from a transcriptional coactivator to a corepressor of nuclear factor (NF)-kappaB response genes in human (TH)1 differentiating cells. V75M, one of many disease-causing mutations occurring in SUMO*motif (72-psipsipsipsiKDxxxxSY-83) of WASp, compromises WASp-SUMOylation, associates with COMMD1 to attenuate NF-kappaB signaling, and recruits histone deacetylases-6 (HDAC6) to p300-marked promoters of NF-kappaB response genes that pattern immunity but not inflammation. Consequently, proteins mediating adaptive immunity (IFNG, STAT1, TLR1) are deficient, whereas those mediating auto inflammation (GM-CSF, TNFAIP2, IL-1beta) are paradoxically increased in TH1 cells expressing SUMOylation-deficient WASp. Moreover, SUMOylation-deficient WASp favors ectopic development of the TH17-like phenotype (?IL17A, IL21, IL22, IL23R, RORC, and CSF2) under TH1-skewing conditions, suggesting a role for WASp in modulating TH1/TH17 plasticity. Notably, pan-histone deacetylase inhibitors lift promoter-specific repression imposed by SUMOylation-deficient WASp and restore misregulated gene expression. Our findings uncovering a SUMOylation-based mechanism controlling WASp's dichotomous roles in transcription may have implications for personalized therapy for patients carrying mutations that perturb WASp-SUMOylation. PMID- 26261241 TI - Low forced expiratory volume is associated with earlier death in sickle cell anemia. AB - Pulmonary complications result in mortality in adults with sickle cell anemia (SCA). We tested the hypothesis that abnormal pulmonary function was associated with earlier death. A prospective cohort of adults with SCA, followed in the Cooperative Study for Sickle Cell Disease, was constructed using the first pulmonary function test at >21 years of age. Spirometry measures: forced expiratory volume in 1 second (FEV1), forced vital capacity, and total lung capacity were categorized based on age, gender, height, and race. Pulmonary function patterns were categorized based on the American Thoracic Society guidelines using both spirometry and lung volumes. A cohort of 430 adults with SCA, mean age 32.6 +/- 9.5 (range, 21.0-67.8) years at time of first pulmonary function test, and a median follow-up of 5.5 years, was evaluated. A total of 63 deaths occurred. At baseline, 47% had normal, 29% restrictive, 8% obstructive, 2% mixed, and 14% nonspecific lung function patterns. In the final multivariable model, lower FEV1 percent predicted was associated with increased hazard ratio of death (HR per % predicted 1.02; 95% confidence interval [CI] 1.00-1.04; P = .037), as was older age (HR 1.07; 95% CI 1.04-1.10; P < .001), male sex (HR 2.09; 95% CI 1.20-3.65; P = .010), higher lactate dehydrogenase levels (HR per mg/dL 1.002; 95% CI 1.00-1.003; P = .015), and higher acute chest syndrome incidence rate (HR per event/year 10.4; 95% CI 3.11-34.8; P < .001). Presence of obstructive (HR 1.18; 95% CI: 0.44-3.20; P = .740) and restrictive (HR 1.31; 95% CI: 0.64-2.32; P = .557) pulmonary function patterns were not associated with earlier death. Understanding the pathophysiology of a low FEV1 percent predicted in individuals with SCA is warranted, enabling early intervention for those at risk. PMID- 26261242 TI - Monitor to investigate CCGs' contract decision in test case. PMID- 26261243 TI - Transparency rules lead to large fall in positive trial results, analysis finds. PMID- 26261244 TI - Margaret McCartney: The power of patients' stories. PMID- 26261245 TI - A Drop of Blood. PMID- 26261239 TI - Severe chronic primary neutropenia in adults: report on a series of 108 patients. AB - Severe chronic primary neutropenia (CPN) is a rare entity, and long-term outcome and risk factors for infections in severe CPN adults have not been described to date. We report the characteristics and outcomes of 108 severe adult CPN patients enrolled in a multi-institutional observational study. Severe CPN adults were mostly female (78%), and median age at diagnosis was 28.3 years. Diagnosis was fortuitous in 62% of cases. The median absolute neutrophil count (ANC) at diagnosis was 0.4 * 10(9)/L, and median ANC without granulocyte colony stimulating factor (G-CSF) during follow-up was 0.5 * 10(9)/L. Twenty-three of 66 (34.8%) evaluable patients had neutrophil autoantibodies, and 6 of 47 (12.8%) a T cell clone. The presence of neutrophil autoantibodies or T-cell clone was not associated with any specific clinical or biological characteristics. No death or hematologic malignancies occurred, and 44 severe bacterial infections were reported in 27 patients with a median follow-up of 8.3 years. Fifty patients received G-CSF either sporadically (n = 24) or continuously (n = 26) and responded (96%). Nineteen patients received immunosuppressive therapies: overall response (OR) was 41%, and median duration of response was 3 months. At diagnosis, the only predictive factor for the occurrence of severe bacterial infections was an ANC count below 0.2 * 10(9)/L (OR, 0.76). Severe CPN in adults is characterized by a female predominance and a benign outcome with a low rate of severe bacterial infections and no secondary malignancies. G-CSF is efficient and well tolerated but is not required in a majority of patients. PMID- 26261246 TI - Key Opinion Leaders. PMID- 26261248 TI - Surveillance of Childhood Cancer Survivors: A Lifelong Affair. PMID- 26261247 TI - Results of a Phase II Trial of Brentuximab Vedotin for CD30+ Cutaneous T-Cell Lymphoma and Lymphomatoid Papulosis. AB - PURPOSE: Brentuximab vedotin, a monoclonal antibody (cAC10) conjugated to monomethyl auristatin E, targets CD30(+) receptors. This phase II open-label trial was conducted to evaluate safety and efficacy in CD30(+) cutaneous T-cell lymphomas. PATIENTS AND METHODS: Forty-eight patients with CD30(+) lymphoproliferative disorders or mycosis fungoides (MF) received an infusion of 1.8 mg/kg every 21 days. RESULTS: Forty-eight evaluable patients (22 women and 26 men; median age, 59.5 years) had an overall response rate of 73% (95% CI, 60% to 86%; 35 of 48 patients) and complete response rate of 35% (95% CI, 22% to 49%; 17 of 48 patients). Fifteen (54%; 95% CI, 31% to 59%) of 28 patients with MF responded, independent of CD30 expression. In patients with MF/Sezary syndrome, the overall response rate was 50% (five of 10 patients) in patients with low CD30 expression (< 10%), 58% (seven of 12 patients) in patients with medium expression (10% to 50%), and 50% (three of six patients) in patients with high expression (>= 50%). Time to response was 12 weeks (range, 3 to 39 weeks), and duration of response was 32 weeks (range, 3 to 93 weeks). All patients with lymphomatoid papulosis (n = 9) and primary cutaneous anaplastic T-cell lymphomas (n = 2) responded; time to response was 3 weeks (range, 3 to 9 weeks), and median duration of response was 26 weeks (range, 6 to 44 weeks). Soluble baseline CD30 levels were lowest in complete responders (P = .036). Grade 1 to 2 peripheral neuropathy was observed in 65% of patients (95% CI, 52% to 79%; 31 of 48 patients), is still ongoing in 55% of patients (95% CI, 41% to 69%; 17 of 31 patients), and resolved in 45% of patients (95% CI, 31% to 59%; 14 of 31 patients), with a median time to resolution of 41.5 weeks. Grade 3 to 4 events were neutropenia (n = 5), nausea (n = 2), chest pain (n = 2), deep vein thrombosis (n = 1), transaminitis (n = 1), and dehydration (n = 1). Dose reductions to 1.2 mg/kg were instituted as a result of grade 2 neuropathy (n = 6), transaminitis (n = 1), and arthralgias and fatigue (n = 2). CONCLUSION: Brentuximab vedotin is both active and well tolerated in cutaneous T-cell lymphoma and lymphomatoid papulosis, with an overall response rate of 73% and complete response rate of 35%. PMID- 26261249 TI - Prognostic Significance of Diffuse Large B-Cell Lymphoma Cell of Origin: Seeing the Forest and the Trees. PMID- 26261250 TI - A Selfless Act. PMID- 26261252 TI - What Do You Say When She Is No Longer Living With Cancer? PMID- 26261253 TI - Treatment Selection and Survival Outcomes in Early-Stage Diffuse Large B-Cell Lymphoma: Do We Still Need Consolidative Radiotherapy? AB - PURPOSE: The choice between chemotherapy alone and chemotherapy plus consolidative radiotherapy (RT) for diffuse large B-cell lymphoma (DLBCL) remains controversial. We aimed to define factors affecting treatment selection and the resulting survival outcomes. PATIENTS AND METHODS: Using the National Cancer Data Base, we identified 59,255 patients with stages I and II DLBCL treated with multiagent chemotherapy alone or chemotherapy plus consolidative RT between 1998 and 2012. Univariable and multivariable analyses were performed to identify sociodemographic, treatment, and tumor characteristics predictive of overall survival (OS) and treatment use. Propensity-adjusted Cox proportional hazard ratios for survival were used to account for indication bias. RESULTS: Of the 59,255 patients with DLBCL enrolled onto the study, 46% had stage II disease, 42% had extranodal disease, and 58% were more than 60 years of age. Only 39% received combined-modality therapy, and this proportion significantly declined from 47% in 2000 to 32% in 2012 (P < .001). Treatment selection was significantly influenced by race, comorbidity, insurance type, education quartile, facility type, age, stage, B symptoms, distance from treatment facility, and year of diagnosis. The median follow-up time was 60 months (interquartile range, 33 to 93). Estimated 5 year and 10-year OS rates were, respectively, 79% and 59% for all patients, 75% and 55% for patients receiving chemotherapy alone, and 82% and 64% for patients receiving combined-modality therapy (P < .001). Even after adjusting for immortal times and indication bias, combined-modality therapy was associated with better OS (HR, 0.66; 95% CI, 0.61 to 0.71; P < .001) than was chemotherapy alone. CONCLUSION: Use of consolidative RT after multiagent chemotherapy in DLBCL is decreasing in the modern era. Selection of treatment strategy is affected by both classical prognostic features and socioeconomic factors. Abandonment of combined modality therapy in favor of chemotherapy alone negatively affects patient survival. PMID- 26261254 TI - Caution in the Use of Immunohistochemistry for Determination of Cell of Origin in Diffuse Large B-Cell Lymphoma. PMID- 26261251 TI - Contribution of Germline Mutations in the RAD51B, RAD51C, and RAD51D Genes to Ovarian Cancer in the Population. AB - PURPOSE: The aim of this study was to estimate the contribution of deleterious mutations in the RAD51B, RAD51C, and RAD51D genes to invasive epithelial ovarian cancer (EOC) in the population and in a screening trial of individuals at high risk of ovarian cancer. PATIENTS AND METHODS: The coding sequence and splice site boundaries of the three RAD51 genes were sequenced and analyzed in germline DNA from a case-control study of 3,429 patients with invasive EOC and 2,772 controls as well as in 2,000 unaffected women who were BRCA1/BRCA2 negative from the United Kingdom Familial Ovarian Cancer Screening Study (UK_FOCSS) after quality control analysis. RESULTS: In the case-control study, we identified predicted deleterious mutations in 28 EOC cases (0.82%) compared with three controls (0.11%; P < .001). Mutations in EOC cases were more frequent in RAD51C (14 occurrences, 0.41%) and RAD51D (12 occurrences, 0.35%) than in RAD51B (two occurrences, 0.06%). RAD51C mutations were associated with an odds ratio of 5.2 (95% CI, 1.1 to 24; P = .035), and RAD51D mutations conferred an odds ratio of 12 (95% CI, 1.5 to 90; P = .019). We identified 13 RAD51 mutations (0.65%) in unaffected UK_FOCSS participants (RAD51C, n = 7; RAD51D, n = 5; and RAD51B, n = 1), which was a significantly greater rate than in controls (P < .001); furthermore, RAD51 mutation carriers were more likely than noncarriers to have a family history of ovarian cancer (P < .001). CONCLUSION: These results confirm that RAD51C and RAD51D are moderate ovarian cancer susceptibility genes and suggest that they confer levels of risk of EOC that may warrant their use alongside BRCA1 and BRCA2 in routine clinical genetic testing. PMID- 26261255 TI - Outcomes of Nonmyeloablative HLA-Haploidentical Blood or Marrow Transplantation With High-Dose Post-Transplantation Cyclophosphamide in Older Adults. AB - PURPOSE: Recent advances in nonmyeloablative (NMA), related HLA-haploidentical blood or marrow transplantation (haplo-BMT) have expanded the donor pool. This study evaluated the effect of age on NMA haplo-BMT outcomes in patients age 50 to 75 years. PATIENTS AND METHODS: A retrospective analysis was performed of 271 consecutive patients with hematologic malignancies, age 50 to 75 years, who received NMA, T-cell-replete haplo-BMT with high-dose post-transplantation cyclophosphamide. RESULTS: The median age was 61 years, with 115 patients (42%) age 50 to 59, 129 (48%) age 60 to 69, and 27 (10%) age 70 to 75 years. Overall, 84% of patients had intermediate- or high-/very high-risk disease. The 6-month probabilities of grade 3 or 4 acute graft-versus-host disease (GVHD) and nonrelapse mortality (NRM) were 3% and 8%, respectively. Patients in their 50s, 60s, and 70s had 6-month NRM probabilities of 8%, 9%, and 7%, respectively (P=.20). With a median follow-up of 4 years, corresponding 3-year progression free survival probabilities were 39%, 35%, and 33% (P=.65), and corresponding 3 year overall survival probabilities were 48%, 45%, and 44% (P=.66). Three-year progression-free survival probabilities were 40% in acute myeloid leukemia (n=65), 39% in aggressive non-Hodgkin lymphoma (n=83), and 37% in indolent or mantle-cell lymphoma (n=65). Older patient age was associated with a significantly higher risk of grade 2 to 4 acute GVHD but not grade 3 to 4 acute or chronic GVHD. No statistically significant associations were found between older age (relative to age 50 to 59 years or as a continuous variable) and NRM, relapse, or survival. CONCLUSION: NMA haplo-BMT with post-transplantation cyclophosphamide has encouraging safety and survival outcomes in patients age 50 to 75 years. In patients otherwise fit for BMT, the results support consideration of this approach despite advanced age. PMID- 26261256 TI - Intestinal Obstruction in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study. AB - PURPOSE: For adult survivors of childhood cancer, knowledge about the long-term risk of intestinal obstruction from surgery, chemotherapy, and radiotherapy is limited. METHODS: Intestinal obstruction requiring surgery (IOS) occurring 5 or more years after cancer diagnosis was evaluated in 12,316 5-year survivors in the Childhood Cancer Survivor Study (2,002 with and 10,314 without abdominopelvic tumors) and 4,023 sibling participants. Cumulative incidence of IOS was calculated with second malignant neoplasm, late recurrence, and death as competing risks. Using piecewise exponential models, we assessed the associations of clinical and demographic factors with rate of IOS. RESULTS: Late IOS was reported by 165 survivors (median age at IOS, 19 years; range, 5 to 50 years; median time from diagnosis to IOS, 13 years) and 14 siblings. The cumulative incidence of late IOS at 35 years was 5.8% (95% CI, 4.4% to 7.3%) among survivors with abdominopelvic tumors, 1.0% (95% CI, 0.7% to 1.4%) among those without abdominopelvic tumors, and 0.3% (95% CI, 0.1% to 0.5%) among siblings. Among survivors, abdominopelvic tumor (adjusted rate ratio [ARR], 3.6; 95% CI, 1.9 to 6.8; P < .001) and abdominal/pelvic radiotherapy within 5 years of cancer diagnosis (ARR, 2.4; 95% CI, 1.6 to 3.7; P < .001) increased the rate of late IOS, adjusting for diagnosis year; sex; race/ethnicity; age at diagnosis; age during follow-up (as natural cubic spline); cancer type; and chemotherapy, radiotherapy, and surgery within 5 years of cancer diagnosis. Developing late IOS increased subsequent mortality among survivors (ARR, 1.8; 95% CI, 1.1 to 2.9; P = .016), adjusting for the same factors. CONCLUSION: The long-term risk of IOS and its association with subsequent mortality underscore the need to promote awareness of this complication among patients and providers. PMID- 26261257 TI - Solid Predominant Histologic Subtype in Resected Stage I Lung Adenocarcinoma Is an Independent Predictor of Early, Extrathoracic, Multisite Recurrence and of Poor Postrecurrence Survival. AB - PURPOSE: To examine the significance of the proposed International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) histologic subtypes of lung adenocarcinoma for patterns of recurrence and, among patients who recur following resection of stage I lung adenocarcinoma, for postrecurrence survival (PRS). PATIENTS AND METHODS: We reviewed patients with stage I lung adenocarcinoma who had undergone complete surgical resection from 1999 to 2009 (N = 1,120). Tumors were subtyped by using the IASLC/ATS/ERS classification. The effects of the dominant subtype on recurrence and, among patients who recurred, on PRS were investigated. RESULTS: Of 1,120 patients identified, 188 had recurrent disease, 103 of whom died as a result of lung cancer. Among patients who recurred, 2-year PRS was 45%, and median PRS was 26.1 months. Compared with patients with nonsolid tumors, patients with solid predominant tumors had earlier (P = .007), more extrathoracic (P < .001), and more multisite (P = .011) recurrences. Multivariable analysis of primary tumor factors revealed that, among patients who recurred, solid predominant histologic pattern in the primary tumor (hazard ratio [HR], 1.76; P = .016), age older than 65 years (HR, 1.63; P = .01), and sublobar resection (HR, 1.6; P = .01) were significantly associated with worse PRS. Presence of extrathoracic metastasis (HR, 1.76; P = .013) and age older than 65 years at the time of recurrence (HR, 1.7; P = .014) were also significantly associated with worse PRS. CONCLUSION: In patients with stage I primary lung adenocarcinoma, solid predominant subtype is an independent predictor of early recurrence and, among those patients who recur, of worse PRS. Our findings provide a rationale for investigating adjuvant therapy and identify novel therapeutic targets for patients with solid predominant lung adenocarcinoma. PMID- 26261258 TI - Reply to M. Gleeson et al. PMID- 26261259 TI - Impact of Subsequent Therapies on Outcome of the FIRE-3/AIO KRK0306 Trial: First Line Therapy With FOLFIRI Plus Cetuximab or Bevacizumab in Patients With KRAS Wild-Type Tumors in Metastatic Colorectal Cancer. AB - PURPOSE: We investigated choice and efficacy of subsequent treatment, with special focus on second-line therapy, in the FIRE-3 trial (FOLFIRI plus cetuximab [arm A] or bevacizumab [arm B]) for patients with KRAS wild-type metastatic colorectal cancer. PATIENTS AND METHODS: Start of subsequent-line (second or third) therapy was defined as use of an antitumor drug that was not part of the previous regimen. We evaluated choice, duration, and efficacy of subsequent therapy and determined the impact of subsequent-line treatment on outcome of patients in FIRE-3. RESULTS: Of 592 patients in the intent-to-treat population, 414 (69.9%) received second-line and 256 (43.2%) received third-line therapy. In subsequent treatment lines, 47.1% of patients originally assigned to arm A received bevacizumab, and 52.2% originally assigned to arm B received either cetuximab or panitumumab. Oxaliplatin was subsequently used in 55.9% (arm A) and 53.2% (arm B) of patients. Second-line therapy was administered for a median duration of 5.0 versus 3.2 months (P < .001) in study arm A versus B. Progression free (6.5 v 4.7 months; hazard ratio, 0.68; 95% CI, 0.54 to 0.85; P < .001) and overall survival (16.3 v 13.2 months; hazard ratio, 0.70; 95% CI, 0.55 to 0.88; P = .0021) from start of second-line therapy were longer in patients in arm A compared with arm B. CONCLUSION: Our data suggest that the sequence of drug application might be more important than exposure to single agents. In patients with RAS wild-type tumors, first-line application of anti-epidermal growth factor receptor-directed therapy may represent a favorable condition for promoting effective subsequent therapy including antiangiogenic agents. PMID- 26261260 TI - Risk of Subsequent Neoplasms During the Fifth and Sixth Decades of Life in the Childhood Cancer Survivor Study Cohort. AB - PURPOSE: Survivors of childhood cancer have an increased risk for subsequent neoplasms (SNs), but the incidence beyond the age of 40 years and associations with therapeutic exposures have not been well described. PATIENTS AND METHODS: Among 14,364 survivors of childhood cancer diagnosed between 1970 and 1986, 3,171 had an attained age of 40 years or older at the time of last contact. Cumulative incidence of SNs, standardized incidence ratios (SIRs), excess absolute risk of subsequent malignant neoplasms (SMNs), and relative risks (RRs) for SMNs and nonmelanoma skin cancers were calculated. RESULTS: In total, 679 SNs were diagnosed in patients age 40 years or older. These included 196 SMNs, 419 nonmelanoma skin cancers, 21 nonmalignant meningiomas, and 43 other benign neoplasms. At age 55 years, the cumulative incidence of new SNs and SMNs occurring after age 40 years was 34.6% (95% CI, 28.7 to 40.6) and 16.3% (95% CI, 11.7 to 20.9), respectively. Survivors were twice as likely as the general population to receive a diagnosis of SMN after age 40 years (SIR, 2.2; 95% CI, 1.9 to 2.5). Among SMNs, risk was increased for breast cancer (SIR, 5.5; 95% CI, 4.5 to 6.7), renal cancer (SIR, 3.9; 95% CI, 2.0 to 7.5), soft tissue sarcoma (SIR, 2.6; 95% CI, 1.5 to 4.4), and thyroid cancer (SIR, 1.9; 95% CI, 1.0 to 3.5). Female sex (RR, 1.9; 95% CI, 1.3 to 2.6; P < .001) and therapeutic radiation exposure (RR, 2.2; 95% CI, 1.4 to 3.3; P < .001) were associated with an increased for risk for SMN in multivariable analysis. CONCLUSION: Even after age 40 years, survivors of childhood cancer remain at increased risk for treatment-related SNs. These data suggest the need for life-long monitoring and should inform anticipatory guidance provided to survivors of childhood cancer. PMID- 26261261 TI - Parsing Progress in Breast Cancer. PMID- 26261262 TI - Pseudoprogression and Immune-Related Response in Solid Tumors. PMID- 26261263 TI - Rational Clinical Experiment: Assessing Prior Probability and Its Impact on the Success of Phase II Clinical Trials. AB - PURPOSE: Despite a robust clinical trial enterprise and encouraging phase II results, the vast minority of oncologic drugs in development receive regulatory approval. In addition, clinicians occasionally make therapeutic decisions based on phase II data. Therefore, clinicians, investigators, and regulatory agencies require improved understanding of the implications of positive phase II studies. We hypothesized that prior probability of eventual drug approval was significantly different across GI cancers, with substantial ramifications for the predictive value of phase II studies. METHODS: We conducted a systematic search of phase II studies conducted between 1999 and 2004 and compared studies against US Food and Drug Administration and National Cancer Institute databases of approved indications for drugs tested in those studies. RESULTS: In all, 317 phase II trials were identified and followed for a median of 12.5 years. Following completion of phase III studies, eventual new drug application approval rates varied from 0% (zero of 45) in pancreatic adenocarcinoma to 34.8% (24 of 69) for colon adenocarcinoma. The proportion of drugs eventually approved was correlated with the disease under study (P < .001). The median type I error for all published trials was 0.05, and the median type II error was 0.1, with minimal variation. By using the observed median type I error for each disease, phase II studies have positive predictive values ranging from less than 1% to 90%, depending on primary site of the cancer. CONCLUSION: Phase II trials in different GI malignancies have distinct prior probabilities of drug approval, yielding quantitatively and qualitatively different predictive values with similar statistical designs. Incorporation of prior probability into trial design may allow for more effective design and interpretation of phase II studies. PMID- 26261264 TI - Inequity of access to ACE inhibitors in Swedish heart failure patients: a register-based study. AB - BACKGROUND: Several international studies suggest inequity in access to evidence based heart failure (HF) care. Specifically, studies of ACE inhibitors (ACEIs) point to reduced ACEI access related to female sex, old age and socioeconomic position. Thus far, most studies have either been rather small, lacking diagnostic data, or lacking the possibility to account for several individual based sociodemographic factors. Our aim was to investigate differences, which could reflect inequity in access to ACEIs based on sex, age, socioeconomic status or immigration status in Swedish patients with HF. METHODS: Individually linked register data for all Swedish adults hospitalised for HF in 2005-2010 (n=93,258) were analysed by multivariate regression models to assess the independent risk of female sex, high age, low employment status, low income level, low educational level or foreign country of birth, associated with lack of an ACEI dispensation within 1 year of hospitalisation. Adjustment for possible confounding was made for age, comorbidity, Angiotensin receptor blocker therapy, period and follow-up time. RESULTS: Analysis revealed an adjusted OR for no ACEI dispensation for women of 1.31 (95% CI 1.27 to 1.35); for the oldest patients of 2.71 (95% CI 2.53 to 2.91); and for unemployed patients of 1.59 (95% CI 1.46 to 1.73). CONCLUSIONS: Access to ACEI treatment was reduced in women, older patients and unemployed patients. We conclude that access to ACEIs is inequitable among Swedish patients with HF. Future studies should include clinical data, as well as mortality outcomes in different groups. PMID- 26261265 TI - FLT1 signaling in metastasis-associated macrophages activates an inflammatory signature that promotes breast cancer metastasis. AB - Although the link between inflammation and cancer initiation is well established, its role in metastatic diseases, the primary cause of cancer deaths, has been poorly explored. Our previous studies identified a population of metastasis associated macrophages (MAMs) recruited to the lung that promote tumor cell seeding and growth. Here we show that FMS-like tyrosine kinase 1 (Flt1, also known as VEGFR1) labels a subset of macrophages in human breast cancers that are significantly enriched in metastatic sites. In mouse models of breast cancer pulmonary metastasis, MAMs uniquely express FLT1. Using several genetic models, we show that macrophage FLT1 signaling is critical for metastasis. FLT1 inhibition does not affect MAM recruitment to metastatic lesions but regulates a set of inflammatory response genes, including colony-stimulating factor 1 (CSF1), a central regulator of macrophage biology. Using a gain-of-function approach, we show that CSF1-mediated autocrine signaling in MAMs is downstream of FLT1 and can restore the tumor-promoting activity of FLT1-inhibited MAMs. Thus, CSF1 is epistatic to FLT1, establishing a link between FLT1 and inflammatory responses within breast tumor metastases. Importantly, FLT1 inhibition reduces tumor metastatic efficiency even after initial seeding, suggesting that these pathways represent therapeutic targets in metastatic disease. PMID- 26261267 TI - A stress-responsive NAC transcription factor SNAC3 confers heat and drought tolerance through modulation of reactive oxygen species in rice. AB - Adverse environmental conditions such as high temperature and drought stress greatly limit the growth and production of crops worldwide. Several NAC (NAM, ATAF1/2, and CUC2) proteins have been documented as important regulators in stress responses, but the molecular mechanisms are largely unknown. Here, a stress-responsive NAC gene, SNAC3 (ONAC003, LOC_Os01g09550), conferring drought and heat tolerance in rice is reported. SNAC3 was ubiquitously expressed and its transcript level was induced by drought, high temperature, salinity stress, and abscisic acid (ABA) treatment. Overexpression (OE) of SNAC3 in rice resulted in enhanced tolerance to high temperature, drought, and oxidative stress caused by methyl viologen (MV), whereas suppression of SNAC3 by RNAi resulted in increased sensitivity to these stresses. The SNAC3-OE transgenic plants exhibited significantly lower levels of H2O2, malondiadehyde (MDA), and relative electrolyte leakage than the wild-type control under heat stress conditions, implying that SNAC3 may confer stress tolerance by modulating reactive oxygen species (ROS) homeostasis. Quantitative PCR experiments showed that the expression of a large number of ROS-scavenging genes was dramatically increased in the SNAC3-OE plants, but significantly decreased in the SNAC3-RNAi transgenic plants. Five ROS-associated genes which were up-regulated in SNAC3-OE plants showed co-expression patterns with SNAC3, and three of the co-expressed ROS associated enzyme genes were verified to be direct target genes of SNAC3. These results suggest that SNAC3 plays important roles in stress responses, and it is likely to be useful for engineering crops with improved tolerance to heat and drought stress. PMID- 26261268 TI - Staying green postharvest: how three mutations in the Arabidopsis chlorophyll b reductase gene NYC1 delay degreening by distinct mechanisms. AB - Stresses such as energy deprivation, wounding and water-supply disruption often contribute to rapid deterioration of harvested tissues. To uncover the genetic regulation behind such stresses, a simple assessment system was used to detect senescence mutants in conjunction with two rapid mapping techniques to identify the causal mutations. To demonstrate the power of this approach, immature inflorescences of Arabidopsis plants that contained ethyl methanesulfonate induced lesions were detached and screened for altered timing of dark-induced senescence. Numerous mutant lines displaying accelerated or delayed timing of senescence relative to wild type were discovered. The underlying mutations in three of these were identified using High Resolution Melting analysis to map to a chromosomal arm followed by a whole-genome sequencing-based mapping method, termed 'Needle in the K-Stack', to identify the causal lesions. All three mutations were single base pair changes and occurred in the same gene, NON-YELLOW COLORING1 (NYC1), a chlorophyll b reductase of the short-chain dehydrogenase/reductase (SDR) superfamily. This was consistent with the mutants preferentially retaining chlorophyll b, although substantial amounts of chlorophyll b were still lost. The single base pair mutations disrupted NYC1 function by three distinct mechanisms, one by producing a termination codon, the second by interfering with correct intron splicing and the third by replacing a highly conserved proline with a non-equivalent serine residue. This non synonymous amino acid change, which occurred in the NADPH binding domain of NYC1, is the first example of such a mutation in an SDR protein inhibiting a physiological response in plants. PMID- 26261270 TI - Polypharmacy and clinical outcomes. PMID- 26261266 TI - T cell metabolism drives immunity. AB - Lymphocytes must adapt to a wide array of environmental stressors as part of their normal development, during which they undergo a dramatic metabolic remodeling process. Research in this area has yielded surprising findings on the roles of diverse metabolic pathways and metabolites, which have been found to regulate lymphocyte signaling and influence differentiation, function and fate. In this review, we integrate the latest findings in the field to provide an up-to date resource on lymphocyte metabolism. PMID- 26261271 TI - Polypharmacy and clinical outcomes. PMID- 26261272 TI - Canadian Task Force obesity guidelines are unbalanced. PMID- 26261273 TI - Canadian Task Force obesity guidelines are unbalanced. PMID- 26261274 TI - Let's talk chronic heart failure. PMID- 26261275 TI - Time to rethink EMRs. PMID- 26261276 TI - Health Canada proposes nutrition label changes. PMID- 26261277 TI - Photo Quiz. A 57-Year-Old Mexican Woman With Epigastric Fullness, Weight Loss, and a Liver Mass. PMID- 26261279 TI - Mechanical Forces and Growth in Animal Tissues. AB - Mechanical forces shape biological tissues. They are the effectors of the developmental programs that orchestrate morphogenesis. A lot of effort has been devoted to understanding morphogenetic processes in mechanical terms. In this review, we focus on the interplay between tissue mechanics and growth. We first describe how tissue mechanics affects growth, by influencing the orientation of cell divisions and the signaling pathways that control the rate of volume increase and proliferation. We then address how the mechanical state of a tissue is affected by the patterns of growth. The forward and reverse interactions between growth and mechanics must be investigated in an integrative way if we want to understand how tissues grow and shape themselves. To illustrate this point, we describe examples in which growth homeostasis is achieved by feedback mechanisms that use mechanical forces. PMID- 26261280 TI - Biological Scaling Problems and Solutions in Amphibians. AB - Size is a primary feature of biological systems that varies at many levels, from the organism to its constituent cells and subcellular structures. Amphibians populate some of the extremes in biological size and have provided insight into scaling mechanisms, upper and lower size limits, and their physiological significance. Body size variation is a widespread evolutionary tactic among amphibians, with miniaturization frequently correlating with direct development that occurs without a tadpole stage. The large genomes of salamanders lead to large cell sizes that necessitate developmental modification and morphological simplification. Amphibian extremes at the cellular level have provided insight into mechanisms that accommodate cell-size differences. Finally, how organelles scale to cell size between species and during development has been investigated at the molecular level, because subcellular scaling can be recapitulated using Xenopus in vitro systems. PMID- 26261281 TI - The Influence of Genome and Cell Size on Brain Morphology in Amphibians. AB - In amphibians, nerve cell size is highly correlated with genome size, and increases in genome and cell size cause a retardation of the rate of development of nervous (as well as nonnervous) tissue leading to secondary simplification. This yields an inverse relationship between genome and cell size on the one hand and morphological complexity of the tectum mesencephali as the main visual center, the size of the torus semicircularis as the main auditory center, the size of the amphibian papilla as an important peripheral auditory structure, and the size of the cerebellum as a major sensorimotor center. Nervous structures developing later (e.g., torus and cerebellum) are more affected by secondary simplification than those that develop earlier (e.g., the tectum). This effect is more prominent in salamanders and caecilians than in frogs owing to larger genome and cells sizes in the former two taxa. We hypothesize that because of intragenomic evolutionary processes, important differences in brain morphology can arise independently of specific environmental selection. PMID- 26261283 TI - Size Scaling of Microtubule Assemblies in Early Xenopus Embryos. AB - The first 12 cleavage divisions in Xenopus embryos provide a natural experiment in size scaling, as cell radius decreases ~16-fold with little change in biochemistry. Analyzing both natural cleavage and egg extract partitioned into droplets revealed that mitotic spindle size scales with cell size, with an upper limit in very large cells. We discuss spindle-size scaling in the small- and large-cell regimes with a focus on the "limiting-component" hypotheses. Zygotes and early blastomeres show a scaling mismatch between spindle and cell size. This problem is solved, we argue, by interphase asters that act to position the spindle and transport chromosomes to the center of daughter cells. These tasks are executed by the spindle in smaller cells. We end by discussing possible mechanisms that limit mitotic aster size and promote interphase aster growth to cell-spanning dimensions. PMID- 26261285 TI - In Vitro and In Vivo Characterization of Reactive Intermediates of Corynoline. AB - Corynoline is a 1,3-benzodioxole-containing isoquinoline alkaloid isolated from Corydalis bugeana Turcz., a traditional herbal medicine. Corynoline has reportedly demonstrated multiple pharmacologic properties. Previous studies have also shown that corynoline induced cytotoxicity and inhibited cytochrome P450 (CYP) enzymes, but the mechanisms of the adverse effects remain unknown. The major objective of the present study was to identify reactive metabolites of corynoline responsible for the cytotoxicity and enzyme inhibition. Three oxidative metabolites (M1-M3) were detected by liquid chromatography-tandem mass spectrometry in rat liver microsomal incubations after exposure to corynoline. M1 and M2 were two isomers of catechol derivatives, and M3 was a di-catechol. The M1 M3 metabolites were also observed in urine of rats given corynoline. A total of four N-acetylcysteine (NAC) conjugates (M4-M7) were detected in microsomes containing corynoline, NAC, and NADPH. Apparently, M4 and M5 were derived from M1, M6 resulted from M2, and M7 was a M3-derived NAC conjugate. This indicates that corynoline was bioactivated to ortho-quinone derivatives. No corynoline derived NAC conjugates (M4-M7) were detected in urine of rats given corynoline; however, three corresponding cysteinylglycine conjugates (M8-M10) were observed instead. Recombinant P450 enzyme incubations demonstrated that the CYPs 2C9, 3A4, and 2C19 were mainly involved in metabolic activation of corynoline. The metabolism study facilitates the understanding of corynoline-induced cytotoxicity and P450 enzyme inhibition. PMID- 26261282 TI - The Systemic Control of Growth. AB - Growth is a complex process that is intimately linked to the developmental program to form adults with proper size and proportions. Genetics is an important determinant of growth, as exemplified by the role of local diffusible molecules setting up organ proportions. In addition, organisms use adaptive responses allowing modulating the size of individuals according to environmental cues, for example, nutrition. Here, we describe some of the physiological principles participating in the determination of final individual size. PMID- 26261284 TI - Drug Metabolism by the Host and Gut Microbiota: A Partnership or Rivalry? AB - The importance of the gut microbiome in determining not only overall health, but also in the metabolism of drugs and xenobiotics, is rapidly emerging. It is becoming increasingly clear that the gut microbiota can act in concert with the host cells to maintain intestinal homeostasis, cometabolize drugs and xenobiotics, and alter the expression levels of drug-metabolizing enzymes and transporters and the expression and activity levels of nuclear receptors. In this myriad of activities, the impact of the microbiota may be beneficial or detrimental to the host. Given that the interplay between the gut microbiota and host cells is likely subject to high interindividual variability, this work has tremendous implications for our ability to predict accurately a particular drug's pharmacokinetics and a given patient population's response to drugs. In this issue of Drug Metabolism and Disposition, a series of articles is presented that illustrate the progress and challenges that lie ahead as we unravel the intricacies associated with drug and xenobiotic metabolism by the gut microbiota. These articles highlight the underlying mechanisms that are involved and the use of in vivo and in vitro approaches that are currently available for elucidating the role of the gut microbiota in drug and xenobiotic metabolism. These articles also shed light on exciting new avenues of research that may be pursued as we consider the role of the gut microbiota as an endocrine organ, a component of the brain-gut axis, and whether the gut microbiota is an appropriate and amenable target for new drugs. PMID- 26261287 TI - Ezetimibe provides incremental reduction in risk for cardiovascular events and need for revascularisation following an acute coronary syndrome. PMID- 26261286 TI - Review: Mechanisms of How the Intestinal Microbiota Alters the Effects of Drugs and Bile Acids. AB - Information on the intestinal microbiota has increased exponentially this century because of technical advancements in genomics and metabolomics. Although information on the synthesis of bile acids by the liver and their transformation to secondary bile acids by the intestinal microbiota was the first example of the importance of the intestinal microbiota in biotransforming chemicals, this review will discuss numerous examples of the mechanisms by which the intestinal microbiota alters the pharmacology and toxicology of drugs and other chemicals. More specifically, the altered pharmacology and toxicology of salicylazosulfapridine, digoxin, l-dopa, acetaminophen, caffeic acid, phosphatidyl choline, carnitine, sorivudine, irinotecan, nonsteroidal anti inflammatory drugs, heterocyclic amines, melamine, nitrazepam, and lovastatin will be reviewed. In addition, recent data that the intestinal microbiota alters drug metabolism of the host, especially Cyp3a, as well as the significance and potential mechanisms of this phenomenon are summarized. The review will conclude with an update of bile acid research, emphasizing the bile acid receptors (FXR and TGR5) that regulate not only bile acid synthesis and transport but also energy metabolism. Recent data indicate that by altering the intestinal microbiota, either by diet or drugs, one may be able to minimize the adverse effects of the Western diet by altering the composition of bile acids in the intestine that are agonists or antagonists of FXR and TGR5. Therefore, it may be possible to consider the intestinal microbiota as another drug target. PMID- 26261288 TI - Informed dissent: can we handle internet medicine? PMID- 26261289 TI - Severe secondary mitral regurgitation and left ventricular dysfunction: a 'deadly combination' against which the fight is not over! PMID- 26261292 TI - Much ado about nothing: a case of diffuse vasospam without demonstration of plaque at optical coherence tomography in a STEMI patient. PMID- 26261291 TI - Significance of electrocardiogram recording in high intercostal spaces in patients with early repolarization syndrome. AB - AIMS: Published reports regarding inferolateral early repolarization (ER) syndrome (ERS) before 2013 possibly included patients with Brugada-pattern electrocardiogram (BrP-ECG) recorded only in the high intercostal spaces (HICS). We investigated the significance of HICS ECG recording in ERS patients. METHODS AND RESULTS: Fifty-six patients showing inferolateral ER in the standard ECG and spontaneous ventricular fibrillation (VF) not linked to structural heart disease underwent drug provocation tests by sodium channel blockade with right precordial ECG (V1-V3) recording in the 2nd-4th intercostal spaces. The prevalence and long term outcome of ERS patients with and without BrP-ECG in HICS were investigated. After 18 patients showing type 1 BrP-ECG in the standard ECG were excluded, 38 patients (34 males, mean age; 40.4 +/- 13.6 years) were classified into four groups [group A (n = 6;16%):patients with ER and type 1 BrP-ECG only in HICS, group B (n = 5;13%):ERS with non-type 1 BrP-ECG only in HICS, group C (n = 8;21%):ERS with non-type 1 BrP-ECG in the standard ECG, and group D (n = 19;50%):ERS only, spontaneously or after drug provocation test]. During follow-up of 110.0 +/- 55.4 months, the rate of VF recurrence including electrical storm was significantly higher in groups A (4/6:67%), B (4/5:80%), and C (4/8:50%) compared with D (2/19:11%) (A, B, and C vs. D, P < 0.05). CONCLUSIONS: Approximately 30% of the patients with ERS who had been diagnosed with the previous criteria showed BrP-ECG only in HICS. Ventricular fibrillation mostly recurred in patients showing BrP-ECG in any precordial lead including HICS; these comprised 50% of the ERS cohort. PMID- 26261290 TI - Prognostic significance of infarct core pathology revealed by quantitative non contrast in comparison with contrast cardiac magnetic resonance imaging in reperfused ST-elevation myocardial infarction survivors. AB - AIMS: To assess the prognostic significance of infarct core tissue characteristics using cardiac magnetic resonance (CMR) imaging in survivors of acute ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: We performed an observational prospective single centre cohort study in 300 reperfused STEMI patients (mean +/- SD age 59 +/- 12 years, 74% male) who underwent CMR 2 days and 6 months post-myocardial infarction (n = 267). Native T1 was measured in myocardial regions of interest (n = 288). Adverse remodelling was defined as an increase in left ventricular (LV) end-diastolic volume >=20% at 6 months. All-cause death or first heart failure hospitalization was a pre specified outcome that was assessed during follow-up (median duration 845 days). One hundred and sixty (56%) patients had a hypo-intense infarct core disclosed by native T1. In multivariable regression, infarct core native T1 was inversely associated with adverse remodelling [odds ratio (95% confidence interval (CI)] per 10 ms reduction in native T1: 0.91 (0.82, 0.00); P = 0.061). Thirty (10.4%) of 288 patients died or experienced a heart failure event and 13 of these events occurred post-discharge. Native T1 values (ms) within the hypo-intense infarct core (n = 160 STEMI patients) were inversely associated with the risk of all cause death or first hospitalization for heart failure post-discharge (for a 10 ms increase in native T1: hazard ratio 0.730, 95% CI 0.617, 0.863; P < 0.001) including after adjustment for left ventricular ejection fraction, infarct core T2 and myocardial haemorrhage. The prognostic results for microvascular obstruction were similar. CONCLUSION: Infarct core native T1 represents a novel non-contrast CMR biomarker with potential for infarct characterization and prognostication in STEMI survivors. Confirmatory studies are warranted. CLINICALTRIALS. GOV IDENTIFIER: NCT02072850. PMID- 26261293 TI - Smoked out! PMID- 26261294 TI - A solid mass trapped in the right atrium. PMID- 26261295 TI - Successful transplantation of a donor heart with multiple traumatic defects. PMID- 26261296 TI - Resistant hypertension: what the cardiologist needs to know. AB - Treatment-resistant hypertension (TRH) affects between 3 and 30% of hypertensive patients, and its presence is associated with increased cardiovascular morbidity and mortality. Until recently, the interest on these patients has been limited, because providing care for them is difficult and often frustrating. However, the arrival of new treatment options [i.e. catheter-based renal denervation (RDN) and baroreceptor stimulation] has revitalized the interest in this topic. The very promising results of the initial uncontrolled studies on the blood pressure (BP) lowering effect of RDN in TRH seemed to suggest that this intervention might represent an easy solution for a complex problem. However, subsequently, data from controlled studies have tempered the enthusiasm of the medical community (and the industry). Conversely, these new studies emphasized some seminal aspects on this topic: (i) the key role of 24 h ambulatory BP and arterial stiffness measurement to identify 'true' resistant patients; (ii) the high prevalence of secondary hypertension among this population; and (iii) the difficulty to identify those patients who may profit from device-based interventions. Accordingly, for those patients with documented TRH, the guidelines suggest to refer them to a hypertension specialist/centre in order to perform adequate work up and treatment strategies. The aim of this review is to provide guidance for the cardiologist on how to identify patients with TRH and elucidate the prevailing underlying pathophysiological mechanism(s), to define a strategy for the identification of patients with TRH who may benefit from device-based interventions and discuss results and limitations of these interventions, and finally to briefly summarize the different drug-based treatment strategies. PMID- 26261297 TI - Ultra-low-dose hybrid single photon emission computed tomography and coronary computed tomography angiography: a comprehensive and non-invasive diagnostic workup of suspected coronary artery disease. PMID- 26261298 TI - Magnetic resonance imaging at 1.5-T in a patient with implantable leadless pacemaker. PMID- 26261299 TI - Reciprocal regulation of two G protein-coupled receptors sensing extracellular concentrations of Ca2+ and H. AB - G protein-coupled receptors (GPCRs) are cell surface receptors that detect a wide range of extracellular messengers and convey this information to the inside of cells. Extracellular calcium-sensing receptor (CaSR) and ovarian cancer gene receptor 1 (OGR1) are two GPCRs that sense extracellular Ca(2+) and H(+), respectively. These two ions are key components of the interstitial fluid, and their concentrations change in an activity-dependent manner. Importantly, the interstitial fluid forms part of the microenvironment that influences cell function in health and disease; however, the exact mechanisms through which changes in the microenvironment influence cell function remain largely unknown. We show that CaSR and OGR1 reciprocally inhibit signaling through each other in central neurons, and that this is lost in their transformed counterparts. Furthermore, strong intracellular acidification impairs CaSR function, but potentiates OGR1 function. Thus, CaSR and OGR1 activities can be regulated in a seesaw manner, whereby conditions promoting signaling through one receptor simultaneously inhibit signaling through the other receptor, potentiating the difference in their relative signaling activity. Our results provide insight into how small but consistent changes in the ionic microenvironment of cells can significantly alter the balance between two signaling pathways, which may contribute to disease progression. PMID- 26261300 TI - Continuous evolutionary change in Plio-Pleistocene mammals of eastern Africa. AB - Much debate has revolved around the question of whether the mode of evolutionary and ecological turnover in the fossil record of African mammals was continuous or pulsed, and the degree to which faunal turnover tracked changes in global climate. Here, we assembled and analyzed large specimen databases of the fossil record of eastern African Bovidae (antelopes) and Turkana Basin large mammals. Our results indicate that speciation and extinction proceeded continuously throughout the Pliocene and Pleistocene, as did increases in the relative abundance of arid-adapted bovids, and in bovid body mass. Species durations were similar among clades with different ecological attributes. Occupancy patterns were unimodal, with long and nearly symmetrical origination and extinction phases. A single origination pulse may be present at 2.0-1.75 Ma, but besides this, there is no evidence that evolutionary or ecological changes in the eastern African record tracked rapid, 100,000-y-scale changes in global climate. Rather, eastern African large mammal evolution tracked global or regional climatic trends at long (million year) time scales, while local, basin-scale changes (e.g., tectonic or hydrographic) and biotic interactions ruled at shorter timescales. PMID- 26261301 TI - Quantifying the impact of weak, strong, and super ties in scientific careers. AB - Scientists are frequently faced with the important decision to start or terminate a creative partnership. This process can be influenced by strategic motivations, as early career researchers are pursuers, whereas senior researchers are typically attractors, of new collaborative opportunities. Focusing on the longitudinal aspects of scientific collaboration, we analyzed 473 collaboration profiles using an egocentric perspective that accounts for researcher-specific characteristics and provides insight into a range of topics, from career achievement and sustainability to team dynamics and efficiency. From more than 166,000 collaboration records, we quantify the frequency distributions of collaboration duration and tie strength, showing that collaboration networks are dominated by weak ties characterized by high turnover rates. We use analytic extreme value thresholds to identify a new class of indispensable super ties, the strongest of which commonly exhibit >50% publication overlap with the central scientist. The prevalence of super ties suggests that they arise from career strategies based upon cost, risk, and reward sharing and complementary skill matching. We then use a combination of descriptive and panel regression methods to compare the subset of publications coauthored with a super tie to the subset without one, controlling for pertinent features such as career age, prestige, team size, and prior group experience. We find that super ties contribute to above-average productivity and a 17% citation increase per publication, thus identifying these partnerships--the analog of life partners--as a major factor in science career development. PMID- 26261302 TI - Lexical shifts, substantive changes, and continuity in State of the Union discourse, 1790-2014. AB - This study reveals that the entry into World War I in 1917 indexed the decisive transition to the modern period in American political consciousness, ushering in new objects of political discourse, a more rapid pace of change of those objects, and a fundamental reframing of the main tasks of governance. We develop a strategy for identifying meaningful categories in textual corpora that span long historic durees, where terms, concepts, and language use changes. Our approach is able to account for the fluidity of discursive categories over time, and to analyze their continuity by identifying the discursive stream as the object of interest. PMID- 26261303 TI - Loss of diphthamide pre-activates NF-kappaB and death receptor pathways and renders MCF7 cells hypersensitive to tumor necrosis factor. AB - The diphthamide on human eukaryotic translation elongation factor 2 (eEF2) is the target of ADP ribosylating diphtheria toxin (DT) and Pseudomonas exotoxin A (PE). This modification is synthesized by seven dipthamide biosynthesis proteins (DPH1 DPH7) and is conserved among eukaryotes and archaea. We generated MCF7 breast cancer cell line-derived DPH gene knockout (ko) cells to assess the impact of complete or partial inactivation on diphthamide synthesis and toxin sensitivity, and to address the biological consequence of diphthamide deficiency. Cells with heterozygous gene inactivation still contained predominantly diphthamide-modified eEF2 and were as sensitive to PE and DT as parent cells. Thus, DPH gene copy number reduction does not affect overall diphthamide synthesis and toxin sensitivity. Complete inactivation of DPH1, DPH2, DPH4, and DPH5 generated viable cells without diphthamide. DPH1ko, DPH2ko, and DPH4ko harbored unmodified eEF2 and DPH5ko ACP- (diphthine-precursor) modified eEF2. Loss of diphthamide prevented ADP ribosylation of eEF2, rendered cells resistant to PE and DT, but does not affect sensitivity toward other protein synthesis inhibitors, such as saporin or cycloheximide. Surprisingly, cells without diphthamide (independent of which the DPH gene compromised) were presensitized toward nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-kappaB) and death-receptor pathways without crossing lethal thresholds. In consequence, loss of diphthamide rendered cells hypersensitive toward TNF-mediated apoptosis. This finding suggests a role of diphthamide in modulating NF-kappaB, death receptor, or apoptosis pathways. PMID- 26261304 TI - Discovery and molecular and biocatalytic properties of hydroxynitrile lyase from an invasive millipede, Chamberlinius hualienensis. AB - Hydroxynitrile lyase (HNL) catalyzes the degradation of cyanohydrins and causes the release of hydrogen cyanide (cyanogenesis). HNL can enantioselectively produce cyanohydrins, which are valuable building blocks for the synthesis of fine chemicals and pharmaceuticals, and is used as an important biocatalyst in industrial biotechnology. Currently, HNLs are isolated from plants and bacteria. Because industrial biotechnology requires more efficient and stable enzymes for sustainable development, we must continuously explore other potential enzyme sources for the desired HNLs. Despite the abundance of cyanogenic millipedes in the world, there has been no precise study of the HNLs from these arthropods. Here we report the isolation of HNL from the cyanide-emitting invasive millipede Chamberlinius hualienensis, along with its molecular properties and application in biocatalysis. The purified enzyme displays a very high specific activity in the synthesis of mandelonitrile. It is a glycosylated homodimer protein and shows no apparent sequence identity or homology with proteins in the known databases. It shows biocatalytic activity for the condensation of various aromatic aldehydes with potassium cyanide to produce cyanohydrins and has high stability over a wide range of temperatures and pH values. It catalyzes the synthesis of (R) mandelonitrile from benzaldehyde with a 99% enantiomeric excess, without using any organic solvents. Arthropod fauna comprise 80% of terrestrial animals. We propose that these animals can be valuable resources for exploring not only HNLs but also diverse, efficient, and stable biocatalysts in industrial biotechnology. PMID- 26261305 TI - Experimental evidence that short-range intermolecular aggregation is sufficient for efficient charge transport in conjugated polymers. AB - Efficiency, current throughput, and speed of electronic devices are to a great extent dictated by charge carrier mobility. The classic approach to impart high carrier mobility to polymeric semiconductors has often relied on the assumption that extensive order and crystallinity are needed. Recently, however, this assumption has been challenged, because high mobility has been reported for semiconducting polymers that exhibit a surprisingly low degree of order. Here, we show that semiconducting polymers can be confined into weakly ordered fibers within an inert polymer matrix without affecting their charge transport properties. In these conditions, the semiconducting polymer chains are inhibited from attaining long-range order in the pi-stacking or alkyl-stacking directions, as demonstrated from the absence of significant X-ray diffraction intensity corresponding to these crystallographic directions, yet still remain extended along the backbone direction and aggregate on a local length scale. As a result, the polymer films maintain high mobility even at very low concentrations. Our findings provide a simple picture that clarifies the role of local order and connectivity of domains. PMID- 26261306 TI - Dimerization of elongator protein 1 is essential for Elongator complex assembly. AB - The evolutionarily conserved Elongator complex, which is composed of six subunits elongator protein 1 (Elp1 to -6), plays vital roles in gene regulation. The molecular hallmark of familial dysautonomia (FD) is the splicing mutation of Elp1 [also known as IkappaB kinase complex-associated protein (IKAP)] in the nervous system that is believed to be the primary cause of the devastating symptoms of this disease. Here, we demonstrate that disease-related mutations in Elp1 affect Elongator assembly, and we have determined the structure of the C-terminal portion of human Elp1 (Elp1-CT), which is sufficient for full-length Elp1 dimerization, as well as the structure of the cognate dimerization domain of yeast Elp1 (yElp1-DD). Our study reveals that the formation of the Elp1 dimer contributes to its stability in vitro and in vivo and is required for the assembly of both the human and yeast Elongator complexes. Functional studies suggest that Elp1 dimerization is essential for yeast viability. Collectively, our results identify the evolutionarily conserved dimerization domain of Elp1 and suggest that the pathological mechanisms underlying the onset and progression of Elp1 mutation-related disease may result from impaired Elongator activities. PMID- 26261307 TI - Key driving forces in the biosynthesis of autoinducing peptides required for staphylococcal virulence. AB - Staphylococci produce autoinducing peptides (AIPs) as quorum-sensing signals that regulate virulence. These AIPs feature a thiolactone macrocycle that connects the peptide C terminus to the side chain of an internal cysteine. AIPs are processed from ribosomally synthesized precursors [accessory gene regulator D (AgrD)] through two proteolytic events. Formation of the thiolactone is coupled to the first of these and involves the activity of the integral membrane protease AgrB. This step is expected to be thermodynamically unfavorable, and therefore, it is unclear how AIP-producing bacteria produce sufficient amounts of the thiolactone containing intermediate to drive quorum sensing. Herein, we present the in vitro reconstitution of the AgrB-dependent proteolysis of an AgrD precursor from Staphylococcus aureus. Our data show that efficient thiolactone production is driven by two unanticipated features of the system: (i) membrane association of the thiolactone-containing intermediate, which stabilizes the macrocycle, and (ii) rapid degradation of the C-terminal proteolysis fragment AgrD(C), which affects the reaction equilibrium position. Cell-based studies confirm the intimate link between AIP production and intracellular AgrD(C) levels. Thus, our studies explain the chemical principles that drive AIP production, including uncovering a hitherto unknown link between quorum sensing and peptide turnover. PMID- 26261308 TI - CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses. AB - Th17 responses are critical to a variety of human autoimmune diseases, and therapeutic targeting with monoclonal antibodies against IL-17 and IL-23 has shown considerable promise. Here, we report data to support selective bromodomain blockade of the transcriptional coactivators CBP (CREB binding protein) and p300 as an alternative approach to inhibit human Th17 responses. We show that CBP30 has marked molecular specificity for the bromodomains of CBP and p300, compared with 43 other bromodomains. In unbiased cellular testing on a diverse panel of cultured primary human cells, CBP30 reduced immune cell production of IL-17A and other proinflammatory cytokines. CBP30 also inhibited IL-17A secretion by Th17 cells from healthy donors and patients with ankylosing spondylitis and psoriatic arthritis. Transcriptional profiling of human T cells after CBP30 treatment showed a much more restricted effect on gene expression than that observed with the pan-BET (bromo and extraterminal domain protein family) bromodomain inhibitor JQ1. This selective targeting of the CBP/p300 bromodomain by CBP30 will potentially lead to fewer side effects than with the broadly acting epigenetic inhibitors currently in clinical trials. PMID- 26261309 TI - Disease-associated mutation in SRSF2 misregulates splicing by altering RNA binding affinities. AB - Serine/arginine-rich splicing factor 2 (SRSF2) is an RNA-binding protein that plays important roles in splicing of mRNA precursors. SRSF2 mutations are frequently found in patients with myelodysplastic syndromes and certain leukemias, but how these mutations affect SRSF2 function has only begun to be examined. We used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease to introduce the P95H mutation to SRSF2 in K562 leukemia cells, generating an isogenic model so that splicing alterations can be attributed solely to mutant SRSF2. We found that SRSF2 (P95H) misregulates 548 splicing events (<1% of total). Of these events, 374 involved the inclusion of cassette exons, and the inclusion was either increased (206) or decreased (168). We detected a specific motif (UCCA/UG) enriched in the more included exons and a distinct motif (UGGA/UG) in the more-excluded exons. RNA gel shift assays showed that a mutant SRSF2 derivative bound more tightly than its wild-type counterpart to RNA sites containing UCCAG but bound less tightly to UGGAG sites. Thus in most cases the pattern of exon inclusion or exclusion correlated with stronger or weaker RNA binding, respectively. We further show that the P95H mutation does not affect other functions of SRSF2, i.e., protein protein interactions with key splicing factors. Our results thus demonstrate that the P95H mutation positively or negatively alters the binding affinity of SRSF2 for cognate RNA sites in target transcripts, leading to misregulation of exon inclusion. Our findings shed light on the mechanism of the disease-associated SRSF2 mutation in splicing regulation and also reveal a group of misspliced mRNA isoforms for potential therapeutic targeting. PMID- 26261310 TI - Adaptive aneuploidy protects against thiol peroxidase deficiency by increasing respiration via key mitochondrial proteins. AB - Aerobic respiration is a fundamental energy-generating process; however, there is cost associated with living in an oxygen-rich environment, because partially reduced oxygen species can damage cellular components. Organisms evolved enzymes that alleviate this damage and protect the intracellular milieu, most notably thiol peroxidases, which are abundant and conserved enzymes that mediate hydrogen peroxide signaling and act as the first line of defense against oxidants in nearly all living organisms. Deletion of all eight thiol peroxidase genes in yeast (?8 strain) is not lethal, but results in slow growth and a high mutation rate. Here we characterized mechanisms that allow yeast cells to survive under conditions of thiol peroxidase deficiency. Two independent ?8 strains increased mitochondrial content, altered mitochondrial distribution, and became dependent on respiration for growth but they were not hypersensitive to H2O2. In addition, both strains independently acquired a second copy of chromosome XI and increased expression of genes encoded by it. Survival of ?8 cells was dependent on mitochondrial cytochrome-c peroxidase (CCP1) and UTH1, present on chromosome XI. Coexpression of these genes in ?8 cells led to the elimination of the extra copy of chromosome XI and improved cell growth, whereas deletion of either gene was lethal. Thus, thiol peroxidase deficiency requires dosage compensation of CCP1 and UTH1 via chromosome XI aneuploidy, wherein these proteins support hydroperoxide removal with the reducing equivalents generated by the electron transport chain. To our knowledge, this is the first evidence of adaptive aneuploidy counteracting oxidative stress. PMID- 26261311 TI - Chemical fingerprints encode mother-offspring similarity, colony membership, relatedness, and genetic quality in fur seals. AB - Chemical communication underpins virtually all aspects of vertebrate social life, yet remains poorly understood because of its highly complex mechanistic basis. We therefore used chemical fingerprinting of skin swabs and genetic analysis to explore the chemical cues that may underlie mother-offspring recognition in colonially breeding Antarctic fur seals. By sampling mother-offspring pairs from two different colonies, using a variety of statistical approaches and genotyping a large panel of microsatellite loci, we show that colony membership, mother offspring similarity, heterozygosity, and genetic relatedness are all chemically encoded. Moreover, chemical similarity between mothers and offspring reflects a combination of genetic and environmental influences, the former partly encoded by substances resembling known pheromones. Our findings reveal the diversity of information contained within chemical fingerprints and have implications for understanding mother-offspring communication, kin recognition, and mate choice. PMID- 26261313 TI - Correlating steric hydration forces with water dynamics through surface force and diffusion NMR measurements in a lipid-DMSO-H2O system. AB - Dimethyl sulfoxide (DMSO) is a common solvent and biological additive possessing well-known utility in cellular cryoprotection and lipid membrane permeabilization, but the governing mechanisms at membrane interfaces remain poorly understood. Many studies have focused on DMSO-lipid interactions and the subsequent effects on membrane-phase behavior, but explanations often rely on qualitative notions of DMSO-induced dehydration of lipid head groups. In this work, surface forces measurements between gel-phase dipalmitoylphosphatidylcholine membranes in DMSO-water mixtures quantify the hydration- and solvation-length scales with angstrom resolution as a function of DMSO concentration from 0 mol% to 20 mol%. DMSO causes a drastic decrease in the range of the steric hydration repulsion, leading to an increase in adhesion at a much-reduced intermembrane distance. Pulsed field gradient NMR of the phosphatidylcholine (PC) head group analogs, dimethyl phosphate and tetramethylammonium ions, shows that the ion hydrodynamic radius decreases with increasing DMSO concentration up to 10 mol% DMSO. The complementary measurements indicate that, at concentrations below 10 mol%, the primary effect of DMSO is to decrease the solvated volume of the PC head group and that, from 10 mol% to 20 mol%, DMSO acts to gradually collapse head groups down onto the surface and suppress their thermal motion. This work shows a connection between surface forces, head group conformation and dynamics, and surface water diffusion, with important implications for soft matter and colloidal systems. PMID- 26261312 TI - Breakthrough of SIV strain smE660 challenge in SIV strain mac239-vaccinated rhesus macaques despite potent autologous neutralizing antibody responses. AB - Although the correlates of immunological protection from human immunodeficiency virus or simian immunodeficiency virus infection remain incompletely understood, it is generally believed that medium to high titers of serum neutralizing antibodies (nAbs) against the challenge virus will prevent infection. This paradigm is based on a series of studies in which passive transfer of HIV specific nAbs protected rhesus macaques (RMs) from subsequent mucosal challenge with a chimeric human/simian immunodeficiency virus. However, it is unknown whether nAb titers define protection in the setting of active immunization. Here we determined serum nAb titers against breakthrough transmitted/founder (T/F) SIVsmE660-derived envelope glycoprotein (Env) variants from 14 RMs immunized with SIVmac239-based DNA-prime/modified vaccinia virus Ankara-boost vaccine regimens that included GM-CSF or CD40L adjuvants and conferred significant but incomplete protection against repeated low-dose intrarectal challenge. A single Env variant established infection in all RMs except one, with no identifiable genetic signature associated with vaccination breakthrough compared with T/F Envs from four unvaccinated monkeys. Breakthrough T/F Env pseudoviruses were potently neutralized in vitro by heterologous pooled serum from chronically SIVsmE660 infected monkeys at IC50 titers exceeding 1:1,000,000. Remarkably, the T/F Env pseudoviruses from 13 of 14 monkeys were also susceptible to neutralization by autologous prechallenge serum at in vitro IC50 titers ranging from 1:742 1:10,832. These titers were similar to those observed in vaccinated RMs that remained uninfected. These data suggest that the relationship between serum nAb titers and protection from mucosal SIV challenge in the setting of active immunization is more complex than previously recognized, warranting further studies into the balance between immune activation, target cell availability, and protective antibody responses. PMID- 26261314 TI - Single-sensor multispeaker listening with acoustic metamaterials. AB - Designing a "cocktail party listener" that functionally mimics the selective perception of a human auditory system has been pursued over the past decades. By exploiting acoustic metamaterials and compressive sensing, we present here a single-sensor listening device that separates simultaneous overlapping sounds from different sources. The device with a compact array of resonant metamaterials is demonstrated to distinguish three overlapping and independent sources with 96.67% correct audio recognition. Segregation of the audio signals is achieved using physical layer encoding without relying on source characteristics. This hardware approach to multichannel source separation can be applied to robust speech recognition and hearing aids and may be extended to other acoustic imaging and sensing applications. PMID- 26261315 TI - Disadvantage, self-control, and health. PMID- 26261316 TI - Antibodies targeting human IL1RAP (IL1R3) show therapeutic effects in xenograft models of acute myeloid leukemia. AB - Acute myeloid leukemia (AML) is associated with a poor survival rate, and there is an urgent need for novel and more efficient therapies, ideally targeting AML stem cells that are essential for maintaining the disease. The interleukin 1 receptor accessory protein (IL1RAP; IL1R3) is expressed on candidate leukemic stem cells in the majority of AML patients, but not on normal hematopoietic stem cells. We show here that monoclonal antibodies targeting IL1RAP have strong antileukemic effects in xenograft models of human AML. We demonstrate that effector-cell-mediated killing is essential for the observed therapeutic effects and that natural killer cells constitute a critical human effector cell type. Because IL-1 signaling is important for the growth of AML cells, we generated an IL1RAP-targeting antibody capable of blocking IL-1 signaling and show that this antibody suppresses the proliferation of primary human AML cells. Hence, IL1RAP can be efficiently targeted with an anti-IL1RAP antibody capable of both achieving antibody-dependent cellular cytotoxicity and blocking of IL-1 signaling as modes of action. Collectively, these results provide important evidence in support of IL1RAP as a target for antibody-based treatment of AML. PMID- 26261317 TI - Computational dissection of human episodic memory reveals mental process-specific genetic profiles. AB - Episodic memory performance is the result of distinct mental processes, such as learning, memory maintenance, and emotional modulation of memory strength. Such processes can be effectively dissociated using computational models. Here we performed gene set enrichment analyses of model parameters estimated from the episodic memory performance of 1,765 healthy young adults. We report robust and replicated associations of the amine compound SLC (solute-carrier) transporters gene set with the learning rate, of the collagen formation and transmembrane receptor protein tyrosine kinase activity gene sets with the modulation of memory strength by negative emotional arousal, and of the L1 cell adhesion molecule (L1CAM) interactions gene set with the repetition-based memory improvement. Furthermore, in a large functional MRI sample of 795 subjects we found that the association between L1CAM interactions and memory maintenance revealed large clusters of differences in brain activity in frontal cortical areas. Our findings provide converging evidence that distinct genetic profiles underlie specific mental processes of human episodic memory. They also provide empirical support to previous theoretical and neurobiological studies linking specific neuromodulators to the learning rate and linking neural cell adhesion molecules to memory maintenance. Furthermore, our study suggests additional memory-related genetic pathways, which may contribute to a better understanding of the neurobiology of human memory. PMID- 26261318 TI - A DEMETER-like DNA demethylase governs tomato fruit ripening. AB - In plants, genomic DNA methylation which contributes to development and stress responses can be actively removed by DEMETER-like DNA demethylases (DMLs). Indeed, in Arabidopsis DMLs are important for maternal imprinting and endosperm demethylation, but only a few studies demonstrate the developmental roles of active DNA demethylation conclusively in this plant. Here, we show a direct cause and effect relationship between active DNA demethylation mainly mediated by the tomato DML, SlDML2, and fruit ripening- an important developmental process unique to plants. RNAi SlDML2 knockdown results in ripening inhibition via hypermethylation and repression of the expression of genes encoding ripening transcription factors and rate-limiting enzymes of key biochemical processes such as carotenoid synthesis. Our data demonstrate that active DNA demethylation is central to the control of ripening in tomato. PMID- 26261319 TI - Random bursts determine dynamics of active filaments. AB - Constituents of living or synthetic active matter have access to a local energy supply that serves to keep the system out of thermal equilibrium. The statistical properties of such fluctuating active systems differ from those of their equilibrium counterparts. Using the actin filament gliding assay as a model, we studied how nonthermal distributions emerge in active matter. We found that the basic mechanism involves the interplay between local and random injection of energy, acting as an analog of a thermal heat bath, and nonequilibrium energy dissipation processes associated with sudden jump-like changes in the system's dynamic variables. We show here how such a mechanism leads to a nonthermal distribution of filament curvatures with a non-Gaussian shape. The experimental curvature statistics and filament relaxation dynamics are reproduced quantitatively by stochastic computer simulations and a simple kinetic model. PMID- 26261320 TI - Biologically active LIL proteins built with minimal chemical diversity. AB - We have constructed 26-amino acid transmembrane proteins that specifically transform cells but consist of only two different amino acids. Most proteins are long polymers of amino acids with 20 or more chemically distinct side-chains. The artificial transmembrane proteins reported here are the simplest known proteins with specific biological activity, consisting solely of an initiating methionine followed by specific sequences of leucines and isoleucines, two hydrophobic amino acids that differ only by the position of a methyl group. We designate these proteins containing leucine (L) and isoleucine (I) as LIL proteins. These proteins functionally interact with the transmembrane domain of the platelet derived growth factor beta-receptor and specifically activate the receptor to transform cells. Complete mutagenesis of these proteins identified individual amino acids required for activity, and a protein consisting solely of leucines, except for a single isoleucine at a particular position, transformed cells. These surprisingly simple proteins define the minimal chemical diversity sufficient to construct proteins with specific biological activity and change our view of what can constitute an active protein in a cellular context. PMID- 26261321 TI - Microfluidic screening and whole-genome sequencing identifies mutations associated with improved protein secretion by yeast. AB - There is an increasing demand for biotech-based production of recombinant proteins for use as pharmaceuticals in the food and feed industry and in industrial applications. Yeast Saccharomyces cerevisiae is among preferred cell factories for recombinant protein production, and there is increasing interest in improving its protein secretion capacity. Due to the complexity of the secretory machinery in eukaryotic cells, it is difficult to apply rational engineering for construction of improved strains. Here we used high-throughput microfluidics for the screening of yeast libraries, generated by UV mutagenesis. Several screening and sorting rounds resulted in the selection of eight yeast clones with significantly improved secretion of recombinant alpha-amylase. Efficient secretion was genetically stable in the selected clones. We performed whole genome sequencing of the eight clones and identified 330 mutations in total. Gene ontology analysis of mutated genes revealed many biological processes, including some that have not been identified before in the context of protein secretion. Mutated genes identified in this study can be potentially used for reverse metabolic engineering, with the objective to construct efficient cell factories for protein secretion. The combined use of microfluidics screening and whole genome sequencing to map the mutations associated with the improved phenotype can easily be adapted for other products and cell types to identify novel engineering targets, and this approach could broadly facilitate design of novel cell factories. PMID- 26261322 TI - Interference effects of choice on confidence: Quantum characteristics of evidence accumulation. AB - Decision-making relies on a process of evidence accumulation which generates support for possible hypotheses. Models of this process derived from classical stochastic theories assume that information accumulates by moving across definite levels of evidence, carving out a single trajectory across these levels over time. In contrast, quantum decision models assume that evidence develops over time in a superposition state analogous to a wavelike pattern and that judgments and decisions are constructed by a measurement process by which a definite state of evidence is created from this indefinite state. This constructive process implies that interference effects should arise when multiple responses (measurements) are elicited over time. We report such an interference effect during a motion direction discrimination task. Decisions during the task interfered with subsequent confidence judgments, resulting in less extreme and more accurate judgments than when no decision was elicited. These results provide qualitative and quantitative support for a quantum random walk model of evidence accumulation over the popular Markov random walk model. We discuss the cognitive and neural implications of modeling evidence accumulation as a quantum dynamic system. PMID- 26261324 TI - Early evolution of the angiosperm clade Asteraceae in the Cretaceous of Antarctica. AB - The Asteraceae (sunflowers and daisies) are the most diverse family of flowering plants. Despite their prominent role in extant terrestrial ecosystems, the early evolutionary history of this family remains poorly understood. Here we report the discovery of a number of fossil pollen grains preserved in dinosaur-bearing deposits from the Late Cretaceous of Antarctica that drastically pushes back the timing of assumed origin of the family. Reliably dated to ~76-66 Mya, these specimens are about 20 million years older than previously known records for the Asteraceae. Using a phylogenetic approach, we interpreted these fossil specimens as members of an extinct early diverging clade of the family, associated with subfamily Barnadesioideae. Based on a molecular phylogenetic tree calibrated using fossils, including the ones reported here, we estimated that the most recent common ancestor of the family lived at least 80 Mya in Gondwana, well before the thermal and biogeographical isolation of Antarctica. Most of the early diverging lineages of the family originated in a narrow time interval after the K/P boundary, 60-50 Mya, coinciding with a pronounced climatic warming during the Late Paleocene and Early Eocene, and the scene of a dramatic rise in flowering plant diversity. Our age estimates reduce earlier discrepancies between the age of the fossil record and previous molecular estimates for the origin of the family, bearing important implications in the evolution of flowering plants in general. PMID- 26261323 TI - Structures of two bacterial resistance factors mediating tRNA-dependent aminoacylation of phosphatidylglycerol with lysine or alanine. AB - The cytoplasmic membrane is probably the most important physical barrier between microbes and the surrounding habitat. Aminoacylation of the polar head group of the phospholipid phosphatidylglycerol (PG) catalyzed by Ala-tRNA(Ala)-dependent alanyl-phosphatidylglycerol synthase (A-PGS) or by Lys-tRNA(Lys)-dependent lysyl phosphatidylglycerol synthase (L-PGS) enables bacteria to cope with cationic peptides that are harmful to the integrity of the cell membrane. Accordingly, these synthases also have been designated as multiple peptide resistance factors (MprF). They consist of a separable C-terminal catalytic domain and an N-terminal transmembrane flippase domain. Here we present the X-ray crystallographic structure of the catalytic domain of A-PGS from the opportunistic human pathogen Pseudomonas aeruginosa. In parallel, the structure of the related lysyl phosphatidylglycerol-specific L-PGS domain from Bacillus licheniformis in complex with the substrate analog L-lysine amide is presented. Both proteins reveal a continuous tunnel that allows the hydrophobic lipid substrate PG and the polar aminoacyl-tRNA substrate to access the catalytic site from opposite directions. Substrate recognition of A-PGS versus L-PGS was investigated using misacylated tRNA variants. The structural work presented here in combination with biochemical experiments using artificial tRNA or artificial lipid substrates reveals the tRNA acceptor stem, the aminoacyl moiety, and the polar head group of PG as the main determinants for substrate recognition. A mutagenesis approach yielded the complementary amino acid determinants of tRNA interaction. These results have broad implications for the design of L-PGS and A-PGS inhibitors that could render microbial pathogens more susceptible to antimicrobial compounds. PMID- 26261326 TI - Results of a large-scale randomized behavior change intervention on road safety in Kenya. AB - Road accidents kill 1.3 million people each year, most in the developing world. We test the efficacy of evocative messages, delivered on stickers placed inside Kenyan matatus, or minibuses, in reducing road accidents. We randomize the intervention, which nudges passengers to complain to their drivers directly, across 12,000 vehicles and find that on average it reduces insurance claims rates of matatus by between one-quarter and one-third and is associated with 140 fewer road accidents per year than predicted. Messages promoting collective action are especially effective, and evocative images are an important motivator. Average maximum speeds and average moving speeds are 1-2 km/h lower in vehicles assigned to treatment. We cannot reject the null hypothesis of no placebo effect. We were unable to discern any impact of a complementary radio campaign on insurance claims. Finally, the sticker intervention is inexpensive: we estimate the cost effectiveness of the most impactful stickers to be between $10 and $45 per disability-adjusted life-year saved. PMID- 26261325 TI - Mechanical coupling of the multiple structural elements of the large-conductance mechanosensitive channel during expansion. AB - The prokaryotic mechanosensitive channel of large conductance (MscL) is a pressure-relief valve protecting the cell from lysing during acute osmotic downshock. When the membrane is stretched, MscL responds to the increase of membrane tension and opens a nonselective pore to about 30 A wide, exhibiting a large unitary conductance of ~ 3 nS. A fundamental step toward understanding the gating mechanism of MscL is to decipher the molecular details of the conformational changes accompanying channel opening. By applying fusion-protein strategy and controlling detergent composition, we have solved the structures of an archaeal MscL homolog from Methanosarcina acetivorans trapped in the closed and expanded intermediate states. The comparative analysis of these two new structures reveals significant conformational rearrangements in the different domains of MscL. The large changes observed in the tilt angles of the two transmembrane helices (TM1 and TM2) fit well with the helix-pivoting model derived from the earlier geometric analyses based on the previous structures. Meanwhile, the periplasmic loop region transforms from a folded structure, containing an omega-shaped loop and a short beta-hairpin, to an extended and partly disordered conformation during channel expansion. Moreover, a significant rotating and sliding of the N-terminal helix (N-helix) is coupled to the tilting movements of TM1 and TM2. The dynamic relationships between the N-helix and TM1/TM2 suggest that the N-helix serves as a membrane-anchored stopper that limits the tilts of TM1 and TM2 in the gating process. These results provide direct mechanistic insights into the highly coordinated movement of the different domains of the MscL channel when it expands. PMID- 26261327 TI - Giving behavior of millionaires. AB - This paper studies conditions influencing the generosity of wealthy people. We conduct incentivized experiments with individuals who have at least ?1 million in their bank account. The results show that millionaires are more generous toward low-income individuals in a giving situation when the other participant has no power, than in a strategic setting, where the other participant can punish unfair behavior. Moreover, the level of giving by millionaires is higher than in any other previous study. Our findings have important implications for charities and financial institutions that deal with wealthy individuals. PMID- 26261328 TI - STIM1 enhances SR Ca2+ content through binding phospholamban in rat ventricular myocytes. AB - In ventricular myocytes, the physiological function of stromal interaction molecule 1 (STIM1), an endo/sarcoplasmic reticulum (ER/SR) Ca(2+) sensor, is unclear with respect to its cellular localization, its Ca(2+)-dependent mobilization, and its action on Ca(2+) signaling. Confocal microscopy was used to measure Ca(2+) signaling and to track the cellular movement of STIM1 with mCherry and immunofluorescence in freshly isolated adult rat ventricular myocytes and those in short-term primary culture. We found that endogenous STIM1 was expressed at low but measureable levels along the Z-disk, in a pattern of puncta and linear segments consistent with the STIM1 localizing to the junctional SR (jSR). Depleting SR Ca(2+) using thapsigargin (2-10 uM) changed neither the STIM1 distribution pattern nor its mobilization rate, evaluated by diffusion coefficient measurements using fluorescence recovery after photobleaching. Two dimensional blue native polyacrylamide gel electrophoresis and coimmunoprecipitation showed that STIM1 in the heart exists mainly as a large protein complex, possibly a multimer, which is not altered by SR Ca(2+) depletion. Additionally, we found no store-operated Ca(2+) entry in control or STIM1 overexpressing ventricular myocytes. Nevertheless, STIM1 overexpressing cells show increased SR Ca(2+) content and increased SR Ca(2+) leak. These changes in Ca(2+) signaling in the SR appear to be due to STIM1 binding to phospholamban and thereby indirectly activating SERCA2a (Sarco/endoplasmic reticulum Ca(2+) ATPase). We conclude that STIM1 binding to phospholamban contributes to the regulation of SERCA2a activity in the steady state and rate of SR Ca(2+) leak and that these actions are independent of store-operated Ca(2+) entry, a process that is absent in normal heart cells. PMID- 26261329 TI - Genetic selection by high altitude: Beware of experiments at ambient conditions. PMID- 26261330 TI - Quantitative genomic analysis of RecA protein binding during DNA double-strand break repair reveals RecBCD action in vivo. AB - Understanding molecular mechanisms in the context of living cells requires the development of new methods of in vivo biochemical analysis to complement established in vitro biochemistry. A critically important molecular mechanism is genetic recombination, required for the beneficial reassortment of genetic information and for DNA double-strand break repair (DSBR). Central to recombination is the RecA (Rad51) protein that assembles into a spiral filament on DNA and mediates genetic exchange. Here we have developed a method that combines chromatin immunoprecipitation with next-generation sequencing (ChIP-Seq) and mathematical modeling to quantify RecA protein binding during the active repair of a single DSB in the chromosome of Escherichia coli. We have used quantitative genomic analysis to infer the key in vivo molecular parameters governing RecA loading by the helicase/nuclease RecBCD at recombination hot spots, known as Chi. Our genomic analysis has also revealed that DSBR at the lacZ locus causes a second RecBCD-mediated DSBR event to occur in the terminus region of the chromosome, over 1 Mb away. PMID- 26261331 TI - Geometry and mechanics of two-dimensional defects in amorphous materials. AB - We study the geometry of defects in amorphous materials and their elastic interactions. Defects are defined and characterized by deviations of the material's intrinsic metric from a Euclidian metric. This characterization makes possible the identification of localized defects in amorphous materials, the formulation of a corresponding elastic problem, and its solution in various cases of physical interest. We present a multipole expansion that covers a large family of localized 2D defects. The dipole term, which represents a dislocation, is studied analytically and experimentally. Quadrupoles and higher multipoles correspond to fundamental strain-carrying entities. The interactions between those entities, as well as their interaction with external stress fields, are fundamental to the inelastic behavior of solids. We develop analytical tools to study those interactions. The model, methods, and results presented in this work are all relevant to the study of systems that involve a distribution of localized sources of strain. Examples are plasticity in amorphous materials and mechanical interactions between cells on a flexible substrate. PMID- 26261333 TI - Reply to Nott: Assessing biases in speleothem records of flood events. PMID- 26261332 TI - Unbiased phosphoproteomic method identifies the initial effects of a methacrylic acid copolymer on macrophages. AB - An unbiased phosphoproteomic method was used to identify biomaterial-associated changes in the phosphorylation patterns of macrophage-like cells. The phosphorylation differences between differentiated THP1 (dTHP1) cells treated for 10, 20, or 30 min with a vascular regenerative methacrylic acid (MAA) copolymer or a control methyl methacrylate (MM) copolymer were determined by MS. There were 1,470 peptides (corresponding to 729 proteins) that were differentially phosphorylated in dTHP1 cells treated with the two materials with a greater cellular response to MAA treatment. In addition to identifying pathways (such as integrin signaling and cytoskeletal arrangement) that are well known to change with cell-material interaction, previously unidentified pathways, such as apoptosis and mRNA splicing, were also discovered. PMID- 26261334 TI - Identification of mud flood layers within stalagmites. PMID- 26261335 TI - Concrete ensemble Kalman filters with rigorous catastrophic filter divergence. AB - The ensemble Kalman filter and ensemble square root filters are data assimilation methods used to combine high-dimensional, nonlinear dynamical models with observed data. Ensemble methods are indispensable tools in science and engineering and have enjoyed great success in geophysical sciences, because they allow for computationally cheap low-ensemble-state approximation for extremely high-dimensional turbulent forecast models. From a theoretical perspective, the dynamical properties of these methods are poorly understood. One of the central mysteries is the numerical phenomenon known as catastrophic filter divergence, whereby ensemble-state estimates explode to machine infinity, despite the true state remaining in a bounded region. In this article we provide a breakthrough insight into the phenomenon, by introducing a simple and natural forecast model that transparently exhibits catastrophic filter divergence under all ensemble methods and a large set of initializations. For this model, catastrophic filter divergence is not an artifact of numerical instability, but rather a true dynamical property of the filter. The divergence is not only validated numerically but also proven rigorously. The model cleanly illustrates mechanisms that give rise to catastrophic divergence and confirms intuitive accounts of the phenomena given in past literature. PMID- 26261336 TI - Swift antibodies to counter emerging viruses. PMID- 26261337 TI - Cryptic infection of a broad taxonomic and geographic diversity of tadpoles by Perkinsea protists. AB - The decline of amphibian populations, particularly frogs, is often cited as an example in support of the claim that Earth is undergoing its sixth mass extinction event. Amphibians seem to be particularly sensitive to emerging diseases (e.g., fungal and viral pathogens), yet the diversity and geographic distribution of infectious agents are only starting to be investigated. Recent work has linked a previously undescribed protist with mass-mortality events in the United States, in which infected frog tadpoles have an abnormally enlarged yellowish liver filled with protist cells of a presumed parasite. Phylogenetic analyses revealed that this infectious agent was affiliated with the Perkinsea: a parasitic group within the alveolates exemplified by Perkinsus sp., a "marine" protist responsible for mass-mortality events in commercial shellfish populations. Using small subunit (SSU) ribosomal DNA (rDNA) sequencing, we developed a targeted PCR protocol for preferentially sampling a clade of the Perkinsea. We tested this protocol on freshwater environmental DNA, revealing a wide diversity of Perkinsea lineages in these environments. Then, we used the same protocol to test for Perkinsea-like lineages in livers of 182 tadpoles from multiple families of frogs. We identified a distinct Perkinsea clade, encompassing a low level of SSU rDNA variation different from the lineage previously associated with tadpole mass-mortality events. Members of this clade were present in 38 tadpoles sampled from 14 distinct genera/phylogroups, from five countries across three continents. These data provide, to our knowledge, the first evidence that Perkinsea-like protists infect tadpoles across a wide taxonomic range of frogs in tropical and temperate environments, including oceanic islands. PMID- 26261338 TI - Highly efficient nonprecious metal catalyst prepared with metal-organic framework in a continuous carbon nanofibrous network. AB - Fuel cell vehicles, the only all-electric technology with a demonstrated >300 miles per fill travel range, use Pt as the electrode catalyst. The high price of Pt creates a major cost barrier for large-scale implementation of polymer electrolyte membrane fuel cells. Nonprecious metal catalysts (NPMCs) represent attractive low-cost alternatives. However, a significantly lower turnover frequency at the individual catalytic site renders the traditional carbon supported NPMCs inadequate in reaching the desired performance afforded by Pt. Unconventional catalyst design aiming at maximizing the active site density at much improved mass and charge transports is essential for the next-generation NPMC. We report here a method of preparing highly efficient, nanofibrous NPMC for cathodic oxygen reduction reaction by electrospinning a polymer solution containing ferrous organometallics and zeolitic imidazolate framework followed by thermal activation. The catalyst offers a carbon nanonetwork architecture made of microporous nanofibers decorated by uniformly distributed high-density active sites. In a single-cell test, the membrane electrode containing such a catalyst delivered unprecedented volumetric activities of 3.3 A ? cm(-3) at 0.9 V or 450 A ? cm(-3) extrapolated at 0.8 V, representing the highest reported value in the literature. Improved fuel cell durability was also observed. PMID- 26261339 TI - Genome-wide identification of CCA1 targets uncovers an expanded clock network in Arabidopsis. AB - The circadian clock in Arabidopsis exerts a critical role in timing multiple biological processes and stress responses through the regulation of up to 80% of the transcriptome. As a key component of the clock, the Myb-like transcription factor CIRCADIAN CLOCK ASSOCIATED1 (CCA1) is able to initiate and set the phase of clock-controlled rhythms and has been shown to regulate gene expression by binding directly to the evening element (EE) motif found in target gene promoters. However, the precise molecular mechanisms underlying clock regulation of the rhythmic transcriptome, specifically how clock components connect to clock output pathways, is poorly understood. In this study, using ChIP followed by deep sequencing of CCA1 in constant light (LL) and diel (LD) conditions, more than 1,000 genomic regions occupied by CCA1 were identified. CCA1 targets are enriched for a myriad of biological processes and stress responses, providing direct links to clock-controlled pathways and suggesting that CCA1 plays an important role in regulating a large subset of the rhythmic transcriptome. Although many of these target genes are evening expressed and contain the EE motif, a significant subset is morning phased and enriched for previously unrecognized motifs associated with CCA1 function. Furthermore, this work revealed several CCA1 targets that do not cycle in either LL or LD conditions. Together, our results emphasize an expanded role for the clock in regulating a diverse category of genes and key pathways in Arabidopsis and provide a comprehensive resource for future functional studies. PMID- 26261340 TI - The amino acid sensor GCN2 inhibits inflammatory responses to apoptotic cells promoting tolerance and suppressing systemic autoimmunity. AB - Efficient apoptotic cell clearance and induction of immunologic tolerance is a critical mechanism preventing autoimmunity and associated pathology. Our laboratory has reported that apoptotic cells induce tolerance by a mechanism dependent on the tryptophan catabolizing enzyme indoleamine 2,3 dioxygenase 1 (IDO1) in splenic macrophages (MPhi). The metabolic-stress sensing protein kinase GCN2 is a primary downstream effector of IDO1; thus, we tested its role in apoptotic cell-driven immune suppression. In vitro, expression of IDO1 in MPhis significantly enhanced apoptotic cell-driven IL-10 and suppressed IL-12 production in a GCN2-dependent mechanism. Suppression of IL-12 protein production was due to attenuation of IL-12 mRNA association with polyribosomes inhibiting translation while IL-10 mRNA association with polyribosomes was not affected. In vivo, apoptotic cell challenge drove a rapid, GCN2-dependent stress response in splenic MPhis with increased IL-10 and TGF-beta production, whereas myeloid specific deletion of GCN2 abrogated regulatory cytokine production with provocation of inflammatory T-cell responses to apoptotic cell antigens and failure of long-tolerance induction. Consistent with a role in prevention of apoptotic cell driven autoreactivity, myeloid deletion of GCN2 in lupus-prone mice resulted in increased immune cell activation, humoral autoimmunity, renal pathology, and mortality. In contrast, activation of GCN2 with an agonist significantly reduced anti-DNA autoantibodies and protected mice from disease. Thus, this study implicates a key role for GCN2 signals in regulating the tolerogenic response to apoptotic cells and limiting autoimmunity. PMID- 26261341 TI - The collaborative roots of corruption. AB - Cooperation is essential for completing tasks that individuals cannot accomplish alone. Whereas the benefits of cooperation are clear, little is known about its possible negative aspects. Introducing a novel sequential dyadic die-rolling paradigm, we show that collaborative settings provide fertile ground for the emergence of corruption. In the main experimental treatment the outcomes of the two players are perfectly aligned. Player A privately rolls a die, reports the result to player B, who then privately rolls and reports the result as well. Both players are paid the value of the reports if, and only if, they are identical (e.g., if both report 6, each earns ?6). Because rolls are truly private, players can inflate their profit by misreporting the actual outcomes. Indeed, the proportion of reported doubles was 489% higher than the expected proportion assuming honesty, 48% higher than when individuals rolled and reported alone, and 96% higher than when lies only benefited the other player. Breaking the alignment in payoffs between player A and player B reduced the extent of brazen lying. Despite player B's central role in determining whether a double was reported, modifying the incentive structure of either player A or player B had nearly identical effects on the frequency of reported doubles. Our results highlight the role of collaboration-particularly on equal terms-in shaping corruption. These findings fit a functional perspective on morality. When facing opposing moral sentiments-to be honest vs. to join forces in collaboration-people often opt for engaging in corrupt collaboration. PMID- 26261342 TI - Production diversity and dietary diversity in smallholder farm households. AB - Undernutrition and micronutrient malnutrition remain problems of significant magnitude in large parts of the developing world. Improved nutrition requires not only better access to food for poor population segments, but also higher dietary quality and diversity. Because many of the poor and undernourished people are smallholder farmers, diversifying production on these smallholder farms is widely perceived as a useful approach to improve dietary diversity. However, empirical evidence on the link between production and consumption diversity is scarce. Here, this issue is addressed with household-level data from Indonesia, Kenya, Ethiopia, and Malawi. Regression models show that on-farm production diversity is positively associated with dietary diversity in some situations, but not in all. When production diversity is already high, the association is not significant or even turns negative, because of foregone income benefits from specialization. Analysis of other factors reveals that market access has positive effects on dietary diversity, which are larger than those of increased production diversity. Market transactions also tend to reduce the role of farm diversity for household nutrition. These results suggest that increasing on-farm diversity is not always the most effective way to improve dietary diversity in smallholder households and should not be considered a goal in itself. Additional research is needed to better understand how agriculture and food systems can be made more nutrition sensitive in particular situations. PMID- 26261343 TI - Comanaging fresh produce for nature conservation and food safety. AB - In 2006, a deadly Escherichia coli O157:H7 outbreak in bagged spinach was traced to California's Central Coast region, where >70% of the salad vegetables sold in the United States are produced. Although no definitive cause for the outbreak could be determined, wildlife was implicated as a disease vector. Growers were subsequently pressured to minimize the intrusion of wildlife onto their farm fields by removing surrounding noncrop vegetation. How vegetation removal actually affects foodborne pathogens remains unknown, however. We combined a fine scale land use map with three datasets comprising ~250,000 enterohemorrhagic E. coli (EHEC), generic E. coli, and Salmonella tests in produce, irrigation water, and rodents to quantify whether seminatural vegetation surrounding farmland is associated with foodborne pathogen prevalence in California's Central Coast region. We found that EHEC in fresh produce increased by more than an order of magnitude from 2007 to 2013, despite extensive vegetation clearing at farm field margins. Furthermore, although EHEC prevalence in produce was highest on farms near areas suitable for livestock grazing, we found no evidence of increased EHEC, generic E. coli, or Salmonella near nongrazed, seminatural areas. Rather, pathogen prevalence increased the most on farms where noncrop vegetation was removed, calling into question reforms that promote vegetation removal to improve food safety. These results suggest a path forward for comanaging fresh produce farms for food safety and environmental quality, as federal food safety reforms spread across ~4.5 M acres of US farmland. PMID- 26261344 TI - Elasticity, friction, and pathway of gamma-subunit rotation in FoF1-ATP synthase. AB - We combine molecular simulations and mechanical modeling to explore the mechanism of energy conversion in the coupled rotary motors of FoF1-ATP synthase. A torsional viscoelastic model with frictional dissipation quantitatively reproduces the dynamics and energetics seen in atomistic molecular dynamics simulations of torque-driven gamma-subunit rotation in the F1-ATPase rotary motor. The torsional elastic coefficients determined from the simulations agree with results from independent single-molecule experiments probing different segments of the gamma-subunit, which resolves a long-lasting controversy. At steady rotational speeds of ~ 1 kHz corresponding to experimental turnover, the calculated frictional dissipation of less than k(B)T per rotation is consistent with the high thermodynamic efficiency of the fully reversible motor. Without load, the maximum rotational speed during transitions between dwells is reached at ~ 1 MHz. Energetic constraints dictate a unique pathway for the coupled rotations of the Fo and F1 rotary motors in ATP synthase, and explain the need for the finer stepping of the F1 motor in the mammalian system, as seen in recent experiments. Compensating for incommensurate eightfold and threefold rotational symmetries in Fo and F1, respectively, a significant fraction of the external mechanical work is transiently stored as elastic energy in the gamma-subunit. The general framework developed here should be applicable to other molecular machines. PMID- 26261345 TI - Adaptive evolution of malaria parasites in French Guiana: Reversal of chloroquine resistance by acquisition of a mutation in pfcrt. AB - In regions with high malaria endemicity, the withdrawal of chloroquine (CQ) as first-line treatment of Plasmodium falciparum infections has typically led to the restoration of CQ susceptibility through the reexpansion of the wild-type (WT) allele K76 of the chloroquine resistance transporter gene (pfcrt) at the expense of less fit mutant alleles carrying the CQ resistance (CQR) marker K76T. In low transmission settings, such as South America, drug resistance mutations can attain 100% prevalence, thereby precluding the return of WT parasites after the complete removal of drug pressure. In French Guiana, despite the fixation of the K76T allele, the prevalence of CQR isolates progressively dropped from >90% to <30% during 17 y after CQ withdrawal in 1995. Using a genome-wide association study with CQ-sensitive (CQS) and CQR isolates, we have identified a single mutation in pfcrt encoding a C350R substitution that is associated with the restoration of CQ susceptibility. Genome editing of the CQR reference strain 7G8 to incorporate PfCRT C350R caused a complete loss of CQR. A retrospective molecular survey on 580 isolates collected from 1997 to 2012 identified all C350R mutant parasites as being CQS. This mutation emerged in 2002 and rapidly spread throughout the P. falciparum population. The C350R allele is also associated with a significant decrease in piperaquine susceptibility in vitro, suggesting that piperaquine pressure in addition to potential fitness costs associated with the 7G8-type CQR pfcrt allele may have selected for this mutation. These findings have important implications for understanding the evolutionary dynamics of antimalarial drug resistance. PMID- 26261346 TI - Glassin, a histidine-rich protein from the siliceous skeletal system of the marine sponge Euplectella, directs silica polycondensation. AB - The hexactinellids are a diverse group of predominantly deep sea sponges that synthesize elaborate fibrous skeletal systems of amorphous hydrated silica. As a representative example, members of the genus Euplectella have proved to be useful model systems for investigating structure-function relationships in these hierarchically ordered siliceous network-like composites. Despite recent advances in understanding the mechanistic origins of damage tolerance in these complex skeletal systems, the details of their synthesis have remained largely unexplored. Here, we describe a previously unidentified protein, named "glassin," the main constituent in the water-soluble fraction of the demineralized skeletal elements of Euplectella. When combined with silicic acid solutions, glassin rapidly accelerates silica polycondensation over a pH range of 6-8. Glassin is characterized by high histidine content, and cDNA sequence analysis reveals that glassin shares no significant similarity with any other known proteins. The deduced amino acid sequence reveals that glassin consists of two similar histidine-rich domains and a connecting domain. Each of the histidine-rich domains is composed of three segments: an amino-terminal histidine and aspartic acid-rich sequence, a proline-rich sequence in the middle, and a histidine and threonine-rich sequence at the carboxyl terminus. Histidine always forms HX or HHX repeats, in which most of X positions are occupied by glycine, aspartic acid, or threonine. Recombinant glassin reproduces the silica precipitation activity observed in the native proteins. The highly modular composition of glassin, composed of imidazole, acidic, and hydroxyl residues, favors silica polycondensation and provides insights into the molecular mechanisms of skeletal formation in hexactinellid sponges. PMID- 26261347 TI - MeCP2 regulates the timing of critical period plasticity that shapes functional connectivity in primary visual cortex. AB - Mutations in methyl-CpG-binding protein 2 (MeCP2) cause Rett syndrome, an autism spectrum-associated disorder with a host of neurological and sensory symptoms, but the pathogenic mechanisms remain elusive. Neuronal circuits are shaped by experience during critical periods of heightened plasticity. The maturation of cortical GABA inhibitory circuitry, the parvalbumin(+) (PV(+)) fast-spiking interneurons in particular, is a key component that regulates the initiation and termination of the critical period. Using MeCP2-null mice, we examined experience dependent development of neural circuits in the primary visual cortex. The functional maturation of parvalbumin interneurons was accelerated upon vision onset, as indicated by elevated GABA synthetic enzymes, vesicular GABA transporter, perineuronal nets, and enhanced GABA transmission among PV interneurons. These changes correlated with a precocious onset and closure of critical period and deficient binocular visual function in mature animals. Reduction of GAD67 expression rescued the precocious opening of the critical period, suggesting its major role in MECP2-mediated regulation of experience driven circuit development. Our results identify molecular changes in a defined cortical cell type and link aberrant developmental trajectory to functional deficits in a model of neuropsychiatric disorder. PMID- 26261348 TI - The opportunistic marine pathogen Vibrio parahaemolyticus becomes virulent by acquiring a plasmid that expresses a deadly toxin. AB - Acute hepatopancreatic necrosis disease (AHPND) is a severe, newly emergent penaeid shrimp disease caused by Vibrio parahaemolyticus that has already led to tremendous losses in the cultured shrimp industry. Until now, its disease-causing mechanism has remained unclear. Here we show that an AHPND-causing strain of V. parahaemolyticus contains a 70-kbp plasmid (pVA1) with a postsegregational killing system, and that the ability to cause disease is abolished by the natural absence or experimental deletion of the plasmid-encoded homologs of the Photorhabdus insect-related (Pir) toxins PirA and PirB. We determined the crystal structure of the V. parahaemolyticus PirA and PirB (PirA(vp) and PirB(vp)) proteins and found that the overall structural topology of PirA(vp)/PirB(vp) is very similar to that of the Bacillus Cry insecticidal toxin-like proteins, despite the low sequence identity (<10%). This structural similarity suggests that the putative PirAB(vp) heterodimer might emulate the functional domains of the Cry protein, and in particular its pore-forming activity. The gene organization of pVA1 further suggested that pirAB(vp) may be lost or acquired by horizontal gene transfer via transposition or homologous recombination. PMID- 26261349 TI - Single methylation of 23S rRNA triggers late steps of 50S ribosomal subunit assembly. AB - Ribosome biogenesis requires multiple assembly factors. In Escherichia coli, deletion of RlmE, the methyltransferase responsible for the 2'-O-methyluridine modification at position 2552 (Um2552) in helix 92 of the 23S rRNA, results in slow growth and accumulation of the 45S particle. We demonstrate that the 45S particle that accumulates in DeltarlmE is a genuine precursor that can be assembled into the 50S subunit. Indeed, 50S formation from the 45S precursor could be promoted by RlmE-mediated Um2552 formation in vitro. Ribosomal protein L36 (encoded by rpmJ) was completely absent from the 45S precursor in DeltarlmE, and we observed a strong genetic interaction between rlmE and rpmJ. Structural probing of 23S rRNA and high-salt stripping of 45S components revealed that RlmE mediated methylation promotes interdomain interactions via the association between helices 92 and 71, stabilized by the single 2'-O-methylation of Um2552, in concert with the incorporation of L36, triggering late steps of 50S subunit assembly. PMID- 26261350 TI - Thermophilization of adult and juvenile tree communities in the northern tropical Andes. AB - Climate change is expected to cause shifts in the composition of tropical montane forests towards increased relative abundances of species whose ranges were previously centered at lower, hotter elevations. To investigate this process of "thermophilization," we analyzed patterns of compositional change over the last decade using recensus data from a network of 16 adult and juvenile tree plots in the tropical forests of northern Andes Mountains and adjacent lowlands in northwestern Colombia. Analyses show evidence that tree species composition is strongly linked to temperature and that composition is changing directionally through time, potentially in response to climate change and increasing temperatures. Mean rates of thermophilization [thermal migration rate (TMR), degrees C ? y(-1)] across all censuses were 0.011 degrees C ? y(-1) (95% confidence interval = 0.002-0.022 degrees C ? y(-1)) for adult trees and 0.027 degrees C ? y(-1) (95% confidence interval = 0.009-0.050 degrees C ? y(-1)) for juvenile trees. The fact that thermophilization is occurring in both the adult and juvenile trees and at rates consistent with concurrent warming supports the hypothesis that the observed compositional changes are part of a long-term process, such as global warming, and are not a response to any single episodic event. The observed changes in composition were driven primarily by patterns of tree mortality, indicating that the changes in composition are mostly via range retractions, rather than range shifts or expansions. These results all indicate that tropical forests are being strongly affected by climate change and suggest that many species will be at elevated risk for extinction as warming continues. PMID- 26261352 TI - Results of the early stage PD MED study: revelation or recapitulation? PMID- 26261351 TI - Systems biology definition of the core proteome of metabolism and expression is consistent with high-throughput data. AB - Finding the minimal set of gene functions needed to sustain life is of both fundamental and practical importance. Minimal gene lists have been proposed by using comparative genomics-based core proteome definitions. A definition of a core proteome that is supported by empirical data, is understood at the systems level, and provides a basis for computing essential cell functions is lacking. Here, we use a systems biology-based genome-scale model of metabolism and expression to define a functional core proteome consisting of 356 gene products, accounting for 44% of the Escherichia coli proteome by mass based on proteomics data. This systems biology core proteome includes 212 genes not found in previous comparative genomics-based core proteome definitions, accounts for 65% of known essential genes in E. coli, and has 78% gene function overlap with minimal genomes (Buchnera aphidicola and Mycoplasma genitalium). Based on transcriptomics data across environmental and genetic backgrounds, the systems biology core proteome is significantly enriched in nondifferentially expressed genes and depleted in differentially expressed genes. Compared with the noncore, core gene expression levels are also similar across genetic backgrounds (two times higher Spearman rank correlation) and exhibit significantly more complex transcriptional and posttranscriptional regulatory features (40% more transcription start sites per gene, 22% longer 5'UTR). Thus, genome-scale systems biology approaches rigorously identify a functional core proteome needed to support growth. This framework, validated by using high-throughput datasets, facilitates a mechanistic understanding of systems-level core proteome function through in silico models; it de facto defines a paleome. PMID- 26261353 TI - A new marketplace in Med Ed: innovation or just rebranding? PMID- 26261354 TI - The informant history: a neglected aspect of clinical education and practice. PMID- 26261355 TI - Osteitis fibrosa cystica in primary hyperparathyroidism. PMID- 26261356 TI - Intrathoracic extramedullary hematopoiesis related spontaneous hemothorax. PMID- 26261358 TI - Free boundary problems: the forefront of current and future developments. PMID- 26261357 TI - Reliability of patient-reported outcomes in rheumatoid arthritis patients: an observational prospective study. AB - OBJECTIVE: Patient-reported outcomes (PROs) such as pain, patient global assessment (PGA) and fatigue are regularly assessed in RA patients. In the present study, we aimed to explore the reliability and smallest detectable differences (SDDs) of these PROs, and whether the time between assessments has an impact on reliability. METHODS: Forty RA patients on stable treatment reported the three PROs daily over two subsequent months. We assessed the reliability of these measures by calculating intraclass correlation coefficients (ICCs) and the SDDs for 1-, 7-, 14- and 28-day test-retest intervals. RESULTS: Overall, SDD and ICC were 25 mm and 0.67 for pain, 25 mm and 0.71 for PGA and 30 mm and 0.66 for fatigue, respectively. SDD was higher with longer time period between assessments, ranging from 19 mm (1-day intervals) to 30 mm (28-day intervals) for pain, 19 to 33 mm for PGA, and 26 to 34 mm for fatigue; correspondingly, ICC was smaller with longer intervals, and ranged between the 1- and the 28-day interval from 0.80 to 0.50 for pain, 0.83 to 0.57 for PGA and 0.76 to 0.58 for fatigue. The baseline simplified disease activity index did not have any influence on reliability. Lower baseline PRO scores led to smaller SDDs. CONCLUSION: Reliability of pain, PGA and fatigue measurements is dependent on the tested time interval and the baseline levels. The relatively high SDDs, even for patients in the lowest tertiles of their PROs, indicate potential issues for assessment of the presence of remission. PMID- 26261359 TI - Global stability of steady states in the classical Stefan problem for general boundary shapes. AB - The classical one-phase Stefan problem (without surface tension) allows for a continuum of steady-state solutions, given by an arbitrary (but sufficiently smooth) domain together with zero temperature. We prove global-in-time stability of such steady states, assuming a sufficient degree of smoothness on the initial domain, but without any a priori restriction on the convexity properties of the initial shape. This is an extension of our previous result (Hadzic & Shkoller 2014 Commun. Pure Appl. Math. 68, 689-757 (doi:10.1002/cpa.21522)) in which we studied nearly spherical shapes. PMID- 26261360 TI - Some free boundary problems involving non-local diffusion and aggregation. AB - We report on recent progress in the study of evolution processes involving degenerate parabolic equations which may exhibit free boundaries. The equations we have selected follow two recent trends in diffusion theory: considering anomalous diffusion with long-range effects, which leads to fractional operators or other operators involving kernels with large tails; and the combination of diffusion and aggregation effects, leading to delicate long-term equilibria whose description is still incipient. PMID- 26261361 TI - Euler equation existence, non-uniqueness and mesh converged statistics. AB - We review existence and non-uniqueness results for the Euler equation of fluid flow. These results are placed in the context of physical models and their solutions. Non-uniqueness is in direct conflict with the purpose of practical simulations, so that a mitigating strategy, outlined here, is important. We illustrate these issues in an examination of mesh converged turbulent statistics, with comparison to laboratory experiments. PMID- 26261362 TI - A free boundary approach to shape optimization problems. AB - The analysis of shape optimization problems involving the spectrum of the Laplace operator, such as isoperimetric inequalities, has known in recent years a series of interesting developments essentially as a consequence of the infusion of free boundary techniques. The main focus of this paper is to show how the analysis of a general shape optimization problem of spectral type can be reduced to the analysis of particular free boundary problems. In this survey article, we give an overview of some very recent technical tools, the so-called shape sub- and supersolutions, and show how to use them for the minimization of spectral functionals involving the eigenvalues of the Dirichlet Laplacian, under a volume constraint. PMID- 26261363 TI - Free boundary problems in shock reflection/diffraction and related transonic flow problems. AB - Shock waves are steep wavefronts that are fundamental in nature, especially in high-speed fluid flows. When a shock hits an obstacle, or a flying body meets a shock, shock reflection/diffraction phenomena occur. In this paper, we show how several long-standing shock reflection/diffraction problems can be formulated as free boundary problems, discuss some recent progress in developing mathematical ideas, approaches and techniques for solving these problems, and present some further open problems in this direction. In particular, these shock problems include von Neumann's problem for shock reflection-diffraction by two-dimensional wedges with concave corner, Lighthill's problem for shock diffraction by two dimensional wedges with convex corner, and Prandtl-Meyer's problem for supersonic flow impinging onto solid wedges, which are also fundamental in the mathematical theory of multidimensional conservation laws. PMID- 26261364 TI - A Stefan problem on an evolving surface. AB - We formulate a Stefan problem on an evolving hypersurface and study the well posedness of weak solutions given L(1) data. To do this, we first develop function spaces and results to handle equations on evolving surfaces in order to give a natural treatment of the problem. Then, we consider the existence of solutions for L(infinity) data; this is done by regularization of the nonlinearity. The regularized problem is solved by a fixed point theorem and then uniform estimates are obtained in order to pass to the limit. By using a duality method, we show continuous dependence, which allows us to extend the results to L(1) data. PMID- 26261365 TI - Far-field perturbations of vortex patches. AB - In this paper I investigate the dynamics of vortex patches in the Yudovitch phase space. I derive an approximation for the evolution of the vorticity in the case of nested vortex patches with distant boundaries, and study its long-time behaviour. PMID- 26261366 TI - Incompressible limit of a mechanical model of tumour growth with viscosity. AB - Various models of tumour growth are available in the literature. The first type describe the evolution of the cell number density when considered as a continuous visco-elastic material with growth. The second type describe the tumour as a set, and rules for the free boundary are given related to the classical Hele-Shaw model of fluid dynamics. Following previous papers where the material is described by a purely elastic material, or when active cell motion is included, we make the link between the two types of description considering the 'stiff pressure law' limit. Even though viscosity is a regularizing effect, new mathematical difficulties arise in the visco-elastic case because estimates on the pressure field are weaker and do not immediately imply compactness. For instance, travelling wave solutions and numerical simulations show that the pressure is discontinuous in space, which is not the case for an elastic material. PMID- 26261367 TI - An overview of unconstrained free boundary problems. AB - In this paper, we present a survey concerning unconstrained free boundary problems of type [Formula: see text] where B1 is the unit ball, Omega is an unknown open set, F(1) and F(2) are elliptic operators (admitting regular solutions), and [Formula: see text] is a functions space to be specified in each case. Our main objective is to discuss a unifying approach to the optimal regularity of solutions to the above matching problems, and list several open problems in this direction. PMID- 26261368 TI - Free boundaries in problems with hysteresis. AB - Here, we present a survey concerning parabolic free boundary problems involving a discontinuous hysteresis operator. Such problems describe biological and chemical processes 'with memory' in which various substances interact according to hysteresis law. Our main objective is to discuss the structure of the free boundaries and the properties of the so-called 'strong solutions' belonging to the anisotropic Sobolev class [Formula: see text] with sufficiently large q. Several open problems in this direction are proposed as well. PMID- 26261369 TI - A note on stability shifting for the Muskat problem. AB - In this note, we show that there exist solutions of the Muskat problem that shift stability regimes: they start unstable, then become stable and finally return to the unstable regime. We also exhibit numerical evidence of solutions with medium sized L(infinity) norm of the derivative of the initial condition that develop a turning singularity. PMID- 26261370 TI - Free boundary problems in biology. AB - In this paper, I review several free boundary problems that arise in the mathematical modelling of biological processes. The biological topics are quite diverse: cancer, wound healing, biofilms, granulomas and atherosclerosis. For each of these topics, I describe the biological background and the mathematical model, and then proceed to state mathematical results, including existence and uniqueness theorems, stability and asymptotic limits, and the behaviour of the free boundary. I also suggest, for each of the topics, open mathematical problems. PMID- 26261371 TI - Convergence rates for the classical, thin and fractional elliptic obstacle problems. AB - We review the finite-element approximation of the classical obstacle problem in energy and max-norms and derive error estimates for both the solution and the free boundary. On the basis of recent regularity results, we present an optimal error analysis for the thin obstacle problem. Finally, we discuss the localization of the obstacle problem for the fractional Laplacian and prove quasi optimal convergence rates. PMID- 26261372 TI - Regularity of free boundaries a heuristic retro. AB - This survey concerns regularity theory of a few free boundary problems that have been developed in the past half a century. Our intention is to bring up different ideas and techniques that constitute the fundamentals of the theory. We shall discuss four different problems, where approaches are somewhat different in each case. Nevertheless, these problems can be divided into two groups: (i) obstacle and thin obstacle problem; (ii) minimal surfaces, and cavitation flow of a perfect fluid. In each case, we shall only discuss the methodology and approaches, giving basic ideas and tools that have been specifically designed and tailored for that particular problem. The survey is kept at a heuristic level with mainly geometric interpretation of the techniques and situations in hand. PMID- 26261373 TI - Engaging Physician Learners Through a Web-Based Platform: Individualized End-of Life Education. AB - BACKGROUND: Web-based modules provide a convenient and low-cost education platform, yet should be carefully designed to ensure that learners are actively engaged. In order to improve attitudes and knowledge in end-of-life (EOL) care, we developed a web-based educational module that employed hyperlinks to allow users access to auxiliary resources: clinical guidelines and seminal research papers. METHODS: Participants took pre-test evaluations of attitudes and knowledge regarding EOL care prior to accessing the educational module, and a post-test evaluation following the module intervention. We recorded the type of hyperlinks (guideline or paper) accessed by learners, and stratified participants into groups based on link type accessed (none, either, or both). We used demographic and educational data to develop a multivariate mixed-effects regression analysis to develop adjusted predictions of attitudes and knowledge. RESULTS: 114 individuals participated. The majority had some professional exposure to EOL care (prior instruction 62%; EOL referral 53%; EOL discussion 56%), though most had no family (68%) or personal experience (51%). On bivariate analysis, non-partnered (p = .04), medical student training level (p = .03), prior palliative care referral (p = .02), having a family member (p = .02) and personal experience of EOL care (p < .01) were all associated with linking to auxiliary resources via hyperlinks. When adjusting for confounders, beta coefficient estimates and least squares estimation demonstrated that participants clicking on both hyperlink types were more likely to score higher on all knowledge and attitude items, and demonstrate increased score improvements. CONCLUSION: Auxiliary resources accessible by hyperlink are an effective adjunct to web-based learning in end-of-life care. PMID- 26261374 TI - The Symptoms Prevalence, Medical Interventions, and Health Care Service Needs for Patients With End-Stage Renal Disease in a Renal Palliative Care Program. AB - A retrospective study was conducted to evaluate the symptoms prevalence and interventions initiated in the last 2 weeks of life, health care service utilization, and causes of death of patients with end-stage renal disease (ESRD under a renal palliative care (RPC) program. A total of 335 RPC patients were included, of which 226 patients died during the study period. The 5 most prevalent symptoms were dyspnea (63.7%), fatigue (51.8%), edema (48.2%), pain (44.2%), and anorexia (38.1%); and the 5 most prevalent interventions initiated were oxygen (69.5%), parenteral infusion (67.3%), antibiotics (53.5%), bladder catheterization (44.7%), and analgesic (39.8%) in the last 2 weeks of life. Each patient received 3.5 +/- 4.4 outpatient clinic visit, 3.4 +/- 10.3 home care visits, and 3.1 +/- 2.7 hospital admissions. Besides ESRD (51.8%), the most common causes of death were cardiovascular events (18.6%) and infection (17.2%). PMID- 26261375 TI - Commonly Prescribed Medications Among Patients in Hospice Care for Chronic Obstructive Pulmonary Disease. AB - PURPOSE: End-stage chronic obstructive pulmonary disease (COPD) presents health care providers with challenges of providing optimal palliative care for patients who follow a less predictable trajectory. The objectives of this study were to evaluate medications being prescribed to patients with end-stage COPD, compared to recommendations made by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, and to determine which medications were provided by the hospice organization. METHODS: We retrospectively reviewed our database for medications pertaining to COPD management as stated in the GOLD criteria or those used for symptoms associated with end of life. RESULTS: A total of 745 patients met inclusion criteria, and approximately 63% were prescribed opioids. Prescribing rates for oxygen, short-acting beta2-agonists, and short-acting anticholinergics were 37%, 33%, and 31%, respectively. Systemic and inhaled corticosteroids were prescribed at higher rates of 20% and 18% compared to long acting bronchodilators. DISCUSSION: Medications used for COPD exacerbation management were prescribed at higher rate than those used for maintenance treatment. PMID- 26261376 TI - Ankle-Brachial Index and Cardiovascular Outcome. PMID- 26261377 TI - Obstructive Sleep Apnea and Diabetic Foot: New Responsibilities? PMID- 26261378 TI - Qualitative Evaluation of Cardiovascular Diseases Management in Family Medicine Team in One Year Level. AB - INTRODUCTION: Cardiovascular diseases (CVD) are the leading death cause in modern world and are the most public health problem. WHO program for CVD contains: prevention, command and follow up of CVD in global level. AIM: Investigate CVD frequency in family medicine team in 2012.year (one year period of time) and qualitative management prevention and clinical services management quality of CVD together with recommended standards. PATIENTS AND METHODS: clinical revision of clinical standard practice patients with CVD was provided in Family medicine team in Public Health Centre Tuzla for the period of time from January 01 2012 - December 31 2012. For quality of realized services, AKAZ standards were based for: chapter 2. Health promotion and diseases prevention 2.5. preventive clinical services; chapter 3. Clinical services, standard 3.1. Coronary diseases and standard 3.2. TIA and Stroke. From CVD register next parameters had been used: age, gender, disease diagnose, therapy, blood pressure values, total cholesterol values, beta blockers therapy, anticoagulant therapy prescription, smoker status, stop smoking recommendation and influenza vaccination recommendation. STATISTICAL APPROACH: All results were taken in Excel program and statistically analyzed. Descriptive standard tests were taken with measurement of central tendency and dispersion. For significant differentials achieved with chi2 chances relation was taken (Odds Ratio-OR) with 95% relevant security. All tests were leveled in statistical significant from 95% (p<0,05). RESULTS: Considering total registered habitants number 1448 (males 624 females 824) total diseases of usually CVD in Team 1 family medicine 531 (36,67%). The most frequent disease was hypertension which was presented in 30,31% of registered patients but in total CVD illness was present in 82,67%. In relation with total patients number (531), female prevalence from CVD 345:186 males vs. 65%:35%; P=0,001 and was statistically significantly higher. Almost patients were in age from >=65 years. Nearly all the standards for chapter 2. Health promotion and diseases prevention and chapter 3. Clinical services, standard 3.1. Coronary diseases and standard 3.2. TIA and Stroke are met in larger percentages than the minimum, however, bad quality signs we have found in total cholesterol control were values of total cholesterol were <= 5mmol/l achieved only in 27.58% patients with CVD. Stop smoking recommendation in smokers with TIA and Stroke (total 10 smokers) was registered in 20,00% patients. Indicator was not achieved,(min level 25%). CONCLUSION: Role of family medicine team is extremely important in patient care who suffer from chronically noncontagious diseases such as CVD, as one of them. Considering that in our country preventive programs for CVD are at small level, results of this study are acceptable. Our plans for personal continuous educations and patient educations about healthy life style are pointed for higher or average of achieved standards and of course everything what have to be done should be written in personal dates of patients. PMID- 26261379 TI - Distribution of Risk Factors in Male and Female Primary Health Care Patients with Osteoarthritis in Albania. AB - AIM: We aimed to describe the distribution of the main risk factors among primary health care users diagnosed with osteoarthritis in Albania, a post-communist country in South Eastern Europe. METHODS: Our study involved all individuals who were diagnosed with osteoarthritis over a two-year period (January 2013 - December 2014) in several primary health care centers in Tirana, the Albanian capital. On the whole, during this two-year period, 1179 adult individuals were diagnosed with osteoarthritis (521 men aged 60.1+/-10.6 years and 658 women aged 58.1+/-9.6 years). According to the criteria of the American College of Rheumatology, the diagnosis of osteoarthritis was based on the history of the disease, physical examination, laboratory findings and radiological findings. Binary logistic regression was used to assess the sex-differences regarding the major risk factors among individuals diagnosed with osteoarthritis. RESULTS: In multivariable-adjusted logistic regression models, female gender was inversely associated with smoking (OR=0.39, 95%CI=0.27-0.56), alcohol intake (OR=0.08, 95%CI=0.06-0.10), overweight but not obesity (OR=0.65, 95%CI=0.46-0.91 and OR=0.74, 95%CI=0.46-1.18, respectively), weight lifting (OR=0.38, 95%CI=0.22 0.66) and heavy physical exercise (OR=0.69, 95%CI=0.46-1.03). Conversely, female gender was positively related to genetic factors (OR=2.17, 95%CI=1.55-3.04) and preexisting inflammatory diseases (OR=1.53, 95%CI=0.93-2.53). CONCLUSION: This study offers useful evidence about the distribution of the main risk factors for osteoarthritis in adult individuals diagnosed with osteoarthritis in Albania. This information may support health professionals and decision-makers in Albania for evidence-based health planning and policy formulation in order to control the toll of osteoarthritis in this transitional society. PMID- 26261380 TI - One Year Outcome of Acute Stroke Patients with Sleep Apnea. AB - The aim of this study was to analyze one year outcome of the acute stroke patients with sleep apnea in order to gender and age. METHODS: It was analyzed 110 patients with acute stroke and sleep apnea. Among them 65(59%) were men. Average age of all participant was 65.13+/-9.27 years. The same number and gender distribution of participants with stroke and without apnea were in control group. Evaluation of sleep apnea has been done with: "The Sleep Disorders Questionnaire", "Berlin Questionnaire to identify patients at risk for the sleep apnea syndrome" and "The Epworth Sleepiness Scale". RESULTS: One year after stroke onset survived 91 (82.7%) out of 110 patients with apnea. Average age of survived patients was 63.66+/-8.78 years. Among them 52(80%) were men. In control group, without apnea survived 104 (94.5%) patients with average age of 65.00+/ 8.62 years. Among them 62 (95.4%) were men. In men with apnea there is significantly lower survival range in order to patients without apnea (X(2)=8.22, p=0.004). In women there is no difference. Survival of both gender in patients with apnea (22; 64.7%) was the lowest in group older than 70 years of age. Sex ratio (men : women) was 15 (68.2%):7(58.3%). Survival in both gender in patients without apnea was the same in group older than 70 years of age: 27 (81.2%) out of 33. Average age of patients who died with apnea was significantly higher in order to patients without (t=1.97, p=0.03). CONCLUSION: One year after stroke, significantly more patients survived without (94.5%) than with apnea (82.7%) (p=0.01). In order to sex survived range was significantly (p=0.004) lover in men with apnea than without but in women there is no difference. Survival range of both gender in patients with apnea was the lowest in group older than 70 years (p=0.03). PMID- 26261381 TI - Oral manifestations of Systemic Sclerosis and Correlation with anti-Topoisomerase I Antibodies (SCL-70). AB - INTRODUCTION: Progressive systemic sclerosis (PSS) is a chronic autoimmune illness. Clinical oral manifestations in Scleroderma are very frequent. AIM: To explore the oral manifestations, frequent and rare, to investigate whether there are differences between gender and the observed correlation of changes in relation to Antibodies Anti-Topoisomerase I. MATERIAL AND METHODS: in the study were included 75 patients (65 females and 10 males), their mean age was 45.2+/ 10, duration of illness was around 5.1+/-12 years diagnosed according to the ACR criteria and treated in the period 2010-2013. RESULTS: 98.7% of our patients were ANA positive, whereas 49.3% of them were Anti SCL-70 positive. Patients in 91% of cases had one or more oral manifestations of disease. The most frequent oral manifestations are: small mouth (n = 39), the lingua short frenulum (n = 21), Xerostomia (n = 24) and paradontopathia (n = 16), while more rare are: Telangiectasia (n = 14), decreased interincisal distance (n = 9), missing teeth (n = 9), absorption of dental alveoli (n = 5) and Neuralgia n. trigeminus (n = 3). Oral symptoms have been frequent in patients with Scleroderma, SCL -70 positive but not statistically significant difference. CONCLUSIONS: Oral changes have high frequency in patients with Scleroderma and these changes provide high discomfort of the mouth and lower quality of life. Oral health care to patients with Scleroderma is very important and it affects a lot in reducing the level of disease and increase the quality of life. PMID- 26261382 TI - Hyperglycemia in Critically Ill Patients: Management and Prognosis. AB - INTRODUCTION: Hyperglycemia is a common complication of critical illness. Patients in intensive care unit with stress hyperglycemia have significantly higher mortality (31%) compared to patients with previously confirmed diabetes (10%) or normoglycemia (11.3%). Stress hyperglycemia is associated with increased risk of critical illness polyneuropathy (CIP) and prolonged mechanical ventilation. Intensive monitoring and insulin therapy according to the protocol are an important part of the treatment of critically ill patients. OBJECTIVE: To evaluate the incidence of stress hyperglycemia, complications and outcome in critically ill patients in our Medical intensive care unit. MATERIALS AND METHODS: This study included 100 patients hospitalized in Medical intensive care unit during the period January 2014-March 2015 which were divided into three groups: Diabetes mellitus, stress-hyperglycemia and normoglycemia. During the retrospective-prospective observational clinical investigation the following data was obtained: age, gender, SAPS, admission diagnosis, average daily blood glucose, highest blood glucose level, glycemic variability, vasopressor and corticosteroid therapy, days on mechanical ventilation, total days of hospitalization in Medical intensive care unit, and outcome. RESULTS: Patients with DM treated with a continuous insulin infusion did not have significantly more complications than patients with normoglycemia, unlike patients with stress hyperglycemia, which had more severe prognosis. There was a significant difference between the maximum level of blood glucose in recovered and patients with adverse outcome (p = 0.0277). Glycemic variability (difference between max. and min. blood glucose) was the strongest predictor of adverse outcome. The difference in glycemic variability between the stress-hyperglycemia and normoglycemic group was statistically significant (p = 0.0066). There was no statistically significant difference in duration of mechanical ventilation and total days of hospitalization in the intensive care unit between the groups. CONCLUSION: Understanding of the objectives of glucose regulation and effective glycemic control is essential for the proper optimization of patient outcomes. PMID- 26261384 TI - Recession Vs Myotomy-Comparative Analysis of Two Surgical Procedures of Weakening Inferior Oblique Muscle Overaction. AB - INTRODUCTION: Inferior oblique overaction (IOOA) can be primary or secondary, isolated or combined to other types of horizontal deviation, mostly with esotropias. Surgical weakening of IOOA means several techniques like; recession, myotomy, myectomy, anteroposition etc. GOALS: we analyzed the effect of inferior oblique muscle surgical weakening comparing two groups of patients with primary hypertropia. MATERIAL AND METHODS: In 5-years retrospective study, we observed 33 patients on which we did the surgical procedure of weakening inferior muscle overaction by two methods; recession and myotomy. RESULTS: In total number of 33 patients, there were 57,6% male and 42,4% female patients with average age of 10,6+/-7,5 (in range of 4-36). There was 33,3% of isolated primary hypertropias, and 66,7% combined with esotropias. At 23 (69,9%) patients the recession surgical procedure was done, and with 10 (30,1%) myotomy. Better effect and binocularity was in 65,2% of patients in recession group which was statistically significant with significance level of p<0,0, chi2=5,705; p=0,021. CONCLUSION: Comparing of two surgical procedures of weakening inferior oblique muscles overaction, recession is better procedure than myotomy. PMID- 26261383 TI - The Accuracy of Pain Measurement in Diagnosis of Scaphoid Bone Fractures in Patients with Magnetic Resonance Imaging: Report of 175 Cases. AB - INTRODUCTION: Scaphoid fracture is the most common fracture among the bones of the wrist. Plain radiography has a sensitivity of 59 to 79 percent for the diagnosis of scaphoid fracture after injury. Casting is done to avoid complications in patients with suspected fractures with normal radiography. Magnetic resonance imaging (MRI) has a sensitivity of 100% and a specificity of 99%. To avoid unnecessary casting and high costs, we decided to offer a way more efficient than radiography and less costly than MRI. MATERIAL AND METHODS: In the present study, 175 patients with suspected scaphoid fracture along with snuff box tenderness and normal radiography were enrolled in the study. On arrival, patients' pain score were determined using visual analog scale method with anatomical snuffbox tenderness and then MRI was performed on the patients' wrist and the results were recorded for patient in the check list. The data was then aggregated and analyzed. RESULTS: The result of MRI for fracture was negative for 90.9% and positive for 9.1%. The mean pain score was 7.3 in negative MRI group and 8.75 in positive MRI group, considering a significant difference. ROC curve graph showed that the sensitivity and specificity will be 87% and 57%, respectively for scores 7.5 and higher and 75% and 72%, respectively for scores 8.5 and higher. CONCLUSION: It seems that although this method, beside other criteria in the diagnosis of fractures, can be useful in future studies, it would not be helpful in fracture detection. PMID- 26261385 TI - The Infraorbital Artery in Fetuses: Clinical Relevance in Perforator Flap Surgery. AB - INTRODUCTION: The reconstruction of soft tissue detects in mid facial region are highly demanding. Most challenging region are nasal alla. For full thickness nasal alla defects most authors use nasolabial flap based on facial/angular arcade, but for recidivans tumors the infraorbital perforator flap is a good solution. AIM: The aim of our research was to analyze the number and the course of the infraorbital artery terminal branches. MATERIAL AND METHODS: Material was 60 fetal hemifacial specimens of different gestational ages. Fetuses were fixed in 10% formalin and arterial blood vessels were injected with Micropaque solution (barium sulfate). Samples were further processed by Spalteholz technique, their images captured with digital camera and analyzed. Infraorbital artery was constant artery and had 2 to 4 terminal branches supplying infraorbital region. The majority of its terminal branches were characterized with descending course. Reach anatomical network of infraorbital artery made anastomoses with facial artery. CONCLUSION: Perforator flap based on infraorbital artery had well defined vascular supply with numerous soft tissue branches, which qualify this flap as safe solution for nasal reconstruction. PMID- 26261386 TI - Treatment of Onychomycosis - a Clinical Study. AB - INTRODUCTION: Onychomycosis is a fungal infection of the nail unit. Anatomical and physiological characteristics of the nail apparatus impose the need for long term treatment to achieve complete cure. GOAL: The main goal of this project is to study the effectiveness of several treatment protocols for onychomycosis based on Scoring Clinical Index for Onychomycosis (SCIO). MATERIAL AND METHODS: The study included 133 patients with onychomycosis, diagnosed by KOH microscopy and culture. Based on disease severity, patients were grouped into groups with SCIO values: 6-9, and 12-16. These groups were randomly subdivided to 5 subgroups according to the given treatment protocols: fluconazole 150 mg 1x weekly, itraconazole continual therapy, itraconazole pulse therapy, terbinafine 250 mg/d, and terbinafine + ciclopirox 8% lacquer, respectively. The cure rate was evaluated at the end of 48 week. RESULTS: The obtained cure rates according to the above mentioned protocols were: 92.30%, 81.81%, 83.33%, 90.90%, and 100%, respectively for groups of patients with SCIO values 6 - 9. Within patients with SCIO values 12-16, were achieved cure rates as follows: 78.57%, 78.57%, 75%, 80%, and 86.66%. CONCLUSIONS: There was no statistically significant difference in cure rate between five treatment protocols applied in this study. In patients with high SCIO values is expected a decrease in cure rate. PMID- 26261387 TI - Representation of Streptococcus Pneumoniae in Outpatient Population of Sarajevo Canton. AB - INTRODUCTION: Streptococcus pneumoniae in asymptomatic manner colonize the mucous membranes of the nasopharynx of children and adults, but can cause serious illness in the media which are naturally sterile. In 5-40% of healthy population this bacteria colonize the nasopharyngeal mucosa thanks to the surface adhesin protein, which allow the bacteria to attach to the epithelial cells. The normal nasopharyngeal microflora retains pneumococcus in a small number and does not allow it to express its pathogenic potential and cause disease. If this dominance of the normal microflora is violated, after adherence and local duplication, pneumococcus can spread to the middle ear, sinuses or lungs. Colonization is more common in children than in adults. GOAL: The goal of this study was to determine the prevalence of the carrier state and susceptibility of pneumococcal strains that circulate in the outpatient population of Sarajevo Canton as a potential source of infection. MATERIAL AND METHODS: In the microbiological laboratory of the Institute of Public Health of Canton Sarajevo in the period from July 1, 2013 until April 15, 2014 were analyzed swabs of the nose and nasopharynx, eye and ear from a total of 4109 outpatients. Swabs were inoculated on blood agar nutrient medium. Then was performed catalase test, preparation by Gram and susceptibility test on Optochin. Isolates positive for S. pneumoniae were subjected to in vitro assays to investigate the antimicrobial susceptibility/resistance. RESULTS: Out of 4109 analyzed swabs the pneumococcus positive was 180 (4.38%). Of these, 137 (76.11%) nasal and nasopharyngeal swabs, 33 (18.33%) of the eyes and 10 (5.56%) ear. The highest number of positive swabs were isolated in children aged 6 years and less, a total of 168 (93.33%), in children aged 7-13 years were positive 7 (3.89%), while among respondents aged 14-20 years only 5 (2.78%). CONCLUSIONS: The most common site for isolation of pneumococci is the nose and throat, and the most common carriers of these bacteria are children under 6 years of age. Determining the prevalence of the carrier state contributes to the improvement of preventive measures to reduce the risk of infection and possible sequels. PMID- 26261388 TI - Hematological Changes in Patients Undergoing Coronary Artery Bypass Surgery: a Prospective Study. AB - OBJECTIVES: Removal of pro inflammatory stimuli after CABG, wound closure and the regenerative ability of the bone marrow will ensure a gradual recovery of hematological parameters. The aim of this study was to assess the hematological changes after CABG. MATERIALS AND METHODS: A prospective cohort study included 164 consecutive patients undergoing on pump CABG surgery between January 2012 and January 2013. Patients with primary hematologic disease, emergent or urgent CABG and off-pump CABG were not included. A time line protocol was employed. RESULTS: All patients survived surgery. Average values of erythrocytes, hemoglobin and hematocrit declined, to reach lower values on day 3 after surgery (-33.6 %, -33.1 %, -32.6 % versus preoperative value, p<0.001) and then gradually increased to reach normal values after one month and the preoperative values after three months. The average values of leukocytes and neutrophils increased rapidly to achieve the highest value on day 2, while the average value of lymphocytes decreased quickly to achieve lower value on day 1 after surgery (+74.7 %, +127.1 %, -52.4 % respectively from the preoperative value, p<0.001). The average platelet count decreased to the lowest value on day 2 after surgery (-26.4 % from the preoperative value, p<0.001), after which gradually increased up to +100.8 % of preoperative value on day 14 (p<0.001) and then gradually decreased to reach normal values on day 21 and preoperative values after three months. CONCLUSIONS: Average values of the three peripheral blood cells parameters undergo important changes after CABG, but not life threatening, and regain normal and preoperative values after 1-3 months after surgery. PMID- 26261389 TI - Postoperative Outcome Comparison Between Pudendal Nerve Block and Caudal Block After Lateral Open Internal Sphincterotomy. AB - OBJECTIVE: To assess the postoperative outcome between pudendal nerve block and caudal block after open lateral internal sphincterotomy for chronic anal fissure. METHODS: Our prospective, randomized and double blind investigation included 123 patients, of both sexes, aged 25-56 years, classed I-II by the American society of anesthesiologists and scheduled for elective open internal lateral sphincterotomy for anal fissure at King Hussein hospital, KHMC, Amman, Jordan, during the period from Jan. 2013 to Feb. 2015. Patients were divided into two groups. Group I included 62 patients (GI, n=62) operated under pudendal nerve block with local infiltration anesthesia and group II included 61 patients (GII, n=61) operated under caudal block. Postoperative pain, surgical duration, period of hospital admission, back to regular working activity and 4 weeks evaluation were compared between the two groups. RESULTS: Postoperative outcome was more enhanced in group II but not significant than in group I. Patients in G-I experienced moderate pain for a mean of 5. 3 days in comparison with 4. 3 days in G-II. P>0. 05. Three patients (4. 9%) in G-II in comparison with 5 patients (8. 1%) in G-I had more hospital stay than 24 hours. Patients in G-II went back to normal activity after a mean of 7. 5 days in comparison with 8. 0 days in G-I. CONCLUSION: Undergoing open lateral internal sphincterotomy with the aid of Pudendal nerve block is an excellent, easy and safe alternative anesthesia to caudal anesthesia. PMID- 26261391 TI - The First Report from Bosnia and Herzegovina on Micro-tese Results in Azoospermic Patients. AB - INTRODUCTION: To present results of MicroTese procedure in treatment of male infertility in patients with azoospermia at Bahceci BIH IVF Center during two year period of 2013-2014. METHODS: In the stated time-period, 55 MicroTese surgeries were performed. In 52.7% of the cases, sperm cells were isolated after MicroTese surgery, and in 47.3% of the cases, there was a negative outcome of the procedure. Obtained sperm cells were subjected to cryopreservation. Furthermore, ICSI procedure was performed by use of the obtained sperm cells. RESULTS: Of 29 positive MicroTese surgeries, 21 (72.4%) resulted in clinical pregnancies. Biggest percentage of negative MicroTese procedures happened in patients with cryptorchidism and orchidopexy. CONCLUSION: MicroTese is the most precise and successful method of retrieving sperm cells surgically in men with azoospermia. Our results are within scope of results in referent world centers. PMID- 26261390 TI - Fears and Health Needs of Patients with Diabetes: A Qualitative Research in Rural Population. AB - INTRODUCTION: Insulin-dependent patients are individuals with chronic disease who are well adapted to living and dealing with any health needs and fears arising. An important aspect in the process of adaptation to chronic illness is the provision of nursing care in the early stages of the disease, because this contributes to its acceptance and the early identification and management of potential complications. PURPOSE: To investigate the health needs and self management problems faced by patients with diabetes daily, especially those who use insulin. Furthermore purpose of this study was to investigate the fears experienced by patients in the early stage of the disease, but also in its subsequent development and to study possible differences between sexes. METHODOLOGY: This is a qualitative study, using interpretative phenomenological approach. Fifteen (nine women and six men) insulin-dependent patients, recounted their personal fears and their needs, through semi-structured interviews, which took place in Central Greece. The method used for processing the results is the Mayering one. RESULTS: The analysis of the narratives showed that patients have a variety of fears and needs associated with the diagnosis, treatment, expected consequences, prognosis and everyday life in the management of the disease. Most patients express the concept of need as desire. Care needs, psychological support and education to recognize and prevent hypoglycemia. CONCLUSIONS: Insulin dependent patients express fears and needs in their daily lives. Nurses providing care aimed at enhancing the level of health, while putting self-care information and training them. Patients want the nurse next to them, so that information is continuous and permanent. PMID- 26261392 TI - Hidden Danger of Irrational Abusing Illegal Androgenic-anabolic Steroids in Recreational Athletes Age Under 35 in Bosnia & Herzegovina. AB - INTRODUCTION: Androgenic-anabolic steroids are rarely used by sportsmen who want to improve physical performance in competition sport. Despite that they are well aware of the side effects of anabolic steroids, many young athletes in Bosnia and Herzegovina without competition motivation come in temptation, trying to achieve better muscle proportion and physical performance unknowing consequence of side effects and what is hiding behind. Risk factors such as increasing of lipid levels and arterial hypertension are major factors which have important role in the Pathogenesis of atherosclerosis and are responsible for occurrence of cardiovascular disease even causing a sudden death in young athletes. OBJECTIVE: The aim of the study was to estimate the frequency of misusing of androgenic anabolic steroid drugs in young recreational sportsmen without competition motivation. This study will try to estimate vascular and lipid status, analyzing the side effects of steroids in young recreational athletes under the age of 35, in Bosnia and Herzegovina. METHODS: The study included 70 individuals in period of 2010 till 2015 on recreational exercising program; 35 individuals misusing androgenic anabolic steroids during the period of 5 years were compared with 35 individuals which do not use androgenic anabolic steroids. Non-invasive methods were used in all individual (clinical examination and vascular ultrasound examination of vein system). The routine of training units in both groups was approximately two hours 4-6 times per week. RESULTS: Final analysis has reveal that in androgenic anabolic steroids group in 18 individuals or 55.7% arterial hypertension with hyperlipidemia was more represented, compared with the group without using anabolic steroids, represented by 2 individuals or 5.7% and it was statistically considered significant by using p value less than 0.05. (p<0.05). Statistically dominant population using anabolic steroids drugs are males (100%) or 35 individuals; we did not find females using anabolic steroids and that is why our research was limited to male population. CONCLUSION: Recreational male sportsmen are dominant androgenic anabolic steroids misusers, trying to achieve better muscle proportion and physical performance, they neglect the anabolic steroids side effects which have devastating consequence on vascular system. Benefits of misusing drugs in recreational exercising program in young sportsmen are mostly connected with development of arterial hypertension and hyperlipidemia and the variety of serious health disorders, progressing the pathogenesis of cardiovascular disease. PMID- 26261393 TI - Laparoscopic Wedge Resection of Gastric Stromal Tumor (GIST). AB - INTRODUCTION: Laparoscopic treatment in general, in recent age has proven that it is well associated with low morbidity, mortality, fast recovery, less pain and sound oncologic outcomes. Recent reports from the National Comprehensive Cancer Network (NCCN) GIST Task Force and the GIST Consensus Conference under the auspices of The European Society for Medical Oncology (ESMO) show that laparoscopic resection may be used for small gastric GISTs (< 2 cm in size). CASE REPORT: We report, all the benefits of laparoscopic approach which include short hospitalization, less pain, better cosmetic effect and good oncological outcome, in this case report of 60 year old female patient with gastric GIST larger than 2 cm. PMID- 26261394 TI - Intramural Haemorrhage and Haematoma as the Cause of Ileus of the Small Intestine in a Haemophiliac. AB - INTRODUCTION: The most frequent sites of bleeding in patients with haemophilia are the soft tissues, the joints, the urinary tract, but much more rarely the gastrointestinal tract. The complications of intramural bleeding are acute intestinal obstruction, but also rupture of the haematoma in the lumen or the peritoneal space. CASE REPORT: We present the case of a haemophiliac patient who was admitted as an emergency due to distended abdomen, nausea, vomiting and the clinical picture of ileus. The native abdomen in a standing position presented air fluid levels with moderate distension of the accompanying bowel loops. A nasal probe was inserted and the symptoms of ileus disappeared, but after taking food by mouth, the picture of ileus returned. CT of the abdomen and pelvis was performed, which showed circular, high density thickening of the walls in places in the area of the jejunum, indicating haemorrhage, but also the formation of haematoma in the wall structure. After administering factor VIII, the symptoms of ileus ceased, and the patient recovered completely. CONCLUSION: This unusual presentation of haemophilia with bleeding in the wall of the small intestine is very rare and has only been seen in a few cases in the world. CT diagnosis defined the cause of the obstruction and saved the patient from an unnecessary surgical procedure. PMID- 26261395 TI - Hsp transcript induction is correlated with physiological changes under drought stress in Indian mustard. AB - Brassica juncea is an important oilseed crop and drought stress is major abiotic stress that limits its growth and productivity. RH0116 (drought tolerant) and RH8812 (drought sensitive) genotypes were undertaken to study some of the physiological parameters and hsp gene expression related to stress tolerance under drought stress conditions. Differential response in terms of seed germination, electrolyte leakage, RWC, osmotic potential was observed in the selected genotypes. In vitro seed germination studies using PEG stress treatments indicated reduced seed germination with increasing levels of stress treatment. Electrolyte leakage increased, whereas, relative water content and osmotic potential decreased in stressed seedlings. Expression of hsp gene was found to be upregulated during drought stress as the transcripts were present only in the stressed plants and disappeared upon rehydration. The drought tolerant variety showed higher transcript accumulation as compared to the sensitive variety. The study showed that drought induced changes in gene expression in two contrasting genotypes were consistent with the physiological response. PMID- 26261396 TI - Photosynthetic characteristics of peanut genotypes under excess and deficit irrigation during summer. AB - In a field experiment three irrigation treatments were given to twelve peanut genotypes through drip. At 80 days after sowing (DAS) the amount of irrigation applied was 20 % higher than the evaporative demand (ET) in T1, 25 % less than ET in T2 and 48 % less than ET in T3 against the cumulative evaporative demand of 412 mm. The relative water content (RWC) of peanut leaves reduced by cutting irrigation from 93.5 % in T1 to 91.1 % in T2 and 77.2 % in T3 but, net photosynthetic rate (P N) was higher in T2 (29.6 MUmol m(-2) s(-1)) than T1 (28.6 MUmol m(-2) s(-1)) and T3 (24.3 MUmol m(-2) s(-1)) at 75-80 DAS. Peanut genotype ICGV 91114 showed the highest P N (30.9 MUmol m(-2) s(-1)) which was statistically at par with GG 20, ICGV 86590, TAG 24, SB XI, TMV 2 and TPG 41. The non-photochemical quenching (NPQ) varied with different irrigation treatment with lowest in T2 and highest in T3. The de-epoxidation state (DeS) was 38 % in T1 and T2 but, increased to 47 % in T3 due to the sever water deficit stress. Applying 20 % higher irrigation than the ET demand (T1) does not warrant any extra benefits in terms of higher photosynthesis in peanut at 75-80 DAS. Further, a reduction of 25 % of the ET (T2) in peanut seems to be the ideal condition for photosynthesis and desirable chlorophyll fluorescence parameters at 80 DAS. Girnar 3 and ICGV 91114 showed NPQ value above 2.2 and higher de-epoxidation state, maintained least deviation in Fv/Fm and Fv'/Fm' under severe water deficit condition are promising peanut genotypes. PMID- 26261398 TI - Capsule formation and asymbiotic seed germination in some hybrids of Phalaenopsis, influenced by pollination season and capsule maturity. AB - We explored the influence of pollination season and maturity of capsule on post pollination capsule formation and in vitro asymbiotic seed germination, respectively. Three Phalaenopsis orchid hybrids, namely, 'Athens', 'Moscow' and 'Lusaka' flowers were artificially self-pollinated during winter, spring, summer and fall seasons and the impact of the pollination seasons was evident during capsule formation. It was observed that winter was the most suitable season for pollination of all the three Phalanaeopsis hybrids resulting in 80-88 % capsule formation. During summer, the pollination success rate was 24-28 %, but resulted in successful capsule formation. Season of pollination further delimited the germination efficiency of seeds harvested from capsules of variable maturity levels. Invariably, seeds collected from winter-pollinated capsules performed best in germination compared to other seasons, for instance, 'Moscow' seeds took less than 14 days to germinate from capsules developed following winter pollination. Regarding the influence of capsule maturity on seed germination, we observed that seeds derived from 5-month mature capsules, invariably took least time to germinate than that of the 3-month or 7-month in all three hybrids, e.g., for 'Moscow' it was 13.9 days with a maximum of 90.3 % germination. PMID- 26261397 TI - Mining expressed sequence tags of rapeseed (Brassica napus L.) to predict the drought responsive regulatory network. AB - It is of great significance to understand the regulatory mechanisms by which plants deal with drought stress. Two EST libraries derived from rapeseed (Brassica napus) leaves in non-stressed and drought stress conditions were analyzed in order to obtain the transcriptomic landscape of drought-exposed B. napus plants, and also to identify and characterize significant drought responsive regulatory genes and microRNAs. The functional ontology analysis revealed a substantial shift in the B. napus transcriptome to govern cellular drought responsiveness via different stress-activated mechanisms. The activity of transcription factor and protein kinase modules generally increased in response to drought stress. The 26 regulatory genes consisting of 17 transcription factor genes, eight protein kinase genes and one protein phosphatase gene were identified showing significant alterations in their expressions in response to drought stress. We also found the six microRNAs which were differentially expressed during drought stress supporting the involvement of a post transcriptional level of regulation for B. napus drought response. The drought responsive regulatory network shed light on the significance of some regulatory components involved in biosynthesis and signaling of various plant hormones (abscisic acid, auxin and brassinosteroids), ubiquitin proteasome system, and signaling through Reactive Oxygen Species (ROS). Our findings suggested a complex and multi-level regulatory system modulating response to drought stress in B. napus. PMID- 26261399 TI - Efficacy of RAPD, ISSR and DAMD markers in assessment of genetic variability and population structure of wild Musa acuminata colla. AB - North east India is considered as one of the major biodiversity hotspots worldwide and centre of origin of several plant species including Musa. Musa acuminata Colla is known to be one of the wild progenitors of cultivated bananas and plantains. Three single primer based DNA marker techniques viz., random amplified polymorphic DNA (RAPD), inter simple sequence repeat (ISSR) and directed amplification of minisatellites DNA (DAMD) were used for diversity diagnostics among 25 genotypes of wild M. acuminata collected from Meghalaya province of north east India. A total of 58 primers (26-RAPD, 21-ISSR, and11 DAMD) yielded 451 DNA fragments, of which 395 (87.58 %) were found to be polymorphic in nature. The polymorphic information content (PIC) values were almost identical for each marker system. The resolving power of the marker system was found to be highest in RAPD (3.96) whereas ISSR resolved highest marker index (16.39) in the study. Selected amplicon data obtained through single primer amplification reactions were utilized for determination of diversity within and among the populations of M. acuminata. Nei's genetic differentiation (Gst) value (0.451) indicated higher proportion of the genetic variation within the populations which is supported by the AMOVA analysis (88 %). The study provides insight into the efficacy of RAPD, ISSR and DAMD to analyse the genetic variation existing in the wild Musa germplasm, which can further be exploited for quality trait improvement and domestication of such important horticultural crops. The genetic diversity based population structure may shed light on the genetic basis of speciation and evolution of various species within the genus Musa. PMID- 26261400 TI - Genetic diversity revealed by morphological traits and ISSR markers in 48 Okras (Abelmoschus escullentus L.). AB - Okra is a widely distributed crop in the tropics, subtropics, and warmer areas of the temperate zones. Its major potential uses as a vegetable, oil and protein source, and source of paper pulp and fuel, or biomass are compatible. It is expected to have high value of exploitation and application. Due to the limited number of molecular studies focused on okras, the methods of morphological and ISSR markers were used to analysis the genetic diversity of 48 okras in the present study. The 22 primers were picked for ISSR-PCR, and a total of 154 fragments were amplified with an overall average polymorphism of 54.55 %. We used the 154 markers to construct the dendrogram based on the unweighted pair group method with arithmetic means (UPGMA). A high level of genetic diversity was found among 48 individuals. The 48 Okras was divided into four clusters at Dice's coefficient of 0.19 with clustering analysis. Based on these data of the genetic diversity, it will be possible to exploit the available resources of okra in more valuable ways. PMID- 26261401 TI - Characterization of genetic diversity in chickpea using SSR markers, Start Codon Targeted Polymorphism (SCoT) and Conserved DNA-Derived Polymorphism (CDDP). AB - To evaluate the genetic diversity among 48 genotypes of chickpea comprising cultivars, landraces and internationally developed improved lines genetic distances were evaluated using three different molecular marker techniques: Simple Sequence Repeat (SSR); Start Codon Targeted (SCoT) and Conserved DNA derived Polymorphism (CDDP). Average polymorphism information content (PIC) for SSR, SCoT and CDDP markers was 0.47, 0.45 and 0.45, respectively, and this revealed that three different marker types were equal for the assessment of diversity amongst genotypes. Cluster analysis for SSR and SCoT divided the genotypes in to three distinct clusters and using CDDP markers data, genotypes grouped in to five clusters. There were positive significant correlation (r = 0.43, P < 0.01) between similarity matrix obtained by SCoT and CDDP. Three different marker techniques showed relatively same pattern of diversity across genotypes and using each marker technique it's obvious that diversity pattern and polymorphism for varieties were higher than that of genotypes, and CDDP had superiority over SCoT and SSR markers. These results suggest that efficiency of SSR, SCOT and CDDP markers was relatively the same in fingerprinting of chickpea genotypes. To our knowledge, this is the first detailed report of using targeted DNA region molecular marker (CDDP) for genetic diversity analysis in chickpea in comparison with SCoT and SSR markers. Overall, our results are able to prove the suitability of SCoT and CDDP markers for genetic diversity analysis in chickpea for their high rates of polymorphism and their potential for genome diversity and germplasm conservation. PMID- 26261402 TI - RAPD and ISSR marker mediated genetic polymorphism of two mangroves Bruguiera gymnorrhiza and Heritiera fomes from Indian Sundarbans in relation to their sustainability. AB - Increased salinity distresses some key species severely in Indian Sundarbans. Geomorphic characteristics coupled with demographic obligations have proven to be pivotal factor towards the prevalence of elevated salinity in this zone. Better adaptation to rapid changes in microclimate demands wide range of genetic polymorphism as well. RAPD and ISSR molecular markers were used for this genetic diversity study. Degree of polymorphism was found relatively higher in Bruguiera gymnorrhiza (26.43 % in RAPD and 24.36 % in ISSR) than the other taxa, Heritiera fomes (14.43 and 12.76 % respectively) in case of RAPD and ISSR. Dendrogram constructed based on the similarity matrix showed that for H. fomes, least saline and highest saline zones are positioned in the same clade; whereas in B. gymnorrhiza the higher saline areas were clustered together. Nei's gene diversity (h) as revealed from RAPD and ISSR analysis were found to be 0.0821, 0.0785 and 0.0647, 0.0592 in B. gymnorrhiza and H. fomes respectively. The higher degree of polymorphism as revealed from UPGMA Dendrogram and Nei's genetic diversity might be attributed towards the comfortable growth of B. gymnorrhiza all along the Indian Sundarbans. On the other hand the relatively lesser degree of genetic polymorphism of H. fomes might be attributed towards their precarious status in present days elevated salinity in Indian Sundarbans. PMID- 26261403 TI - Bioaugmentation of Mesorhizobium cicer, Pseudomonas spp. and Piriformospora indica for Sustainable Chickpea Production. AB - Chickpea establishes symbiotic association with Mesorhizobium to fulfill its nitrogen (N) requirement. Integrating chickpea rhizosphere with potential native mesorhizobia and other plant growth promoting microorganisms can contribute multiple benefits to plants. The present investigation was undertaken to study interactions among Piriformospora indica (PI) with potential plant growth promoting rhizobacteria (PGPR) viz. Pseudomonas argentinensis (LPGPR1), Pseudomonas sp. (LPGPR2) along with national check Pseudomons sp. (LK884) and Mesorhizobium cicer (LGR33, MR) to examine the synergistic effect of consortium for improving growth, symbiotic efficiency, nutrient acquisition and yield in two chickpea (Cicer arietinum L.) varieties viz. desi PBG1 and kabuli BG1053. In vitro, seed germination with consortium MR + PI + LPGPR1 was the best compatible treatment followed by MR + PI + LK884 and MR + PI + LPGPR2. Significant improvement in the growth, symbiotic parameters and grain yield was observed with MR + PI + LPGPR1 and MR + PI + LK884 treatments. Significantly high chlorophyll and leghaemoglobin content was recorded with MR + PI + LPGPR1 (1.57 and 1.64 mg g(-1) fresh weight of leaves and 5.19 and 4.39 mg/g(-1) fresh weight of nodules) in desi PBG1 and kabuli BG1053 chickpea varieties, respectively. At 90 DAS, MR + PI + LPGPR1 treatment significantly improved nodule dry weight (ranged between 84.0 and 141.7 mg plant(-1)) as compared to MR alone treatment (ranged between 62.3 and 123.3 mg plant(-1)). Data revealed significant increase in total nitrogen (N) and phosphorus (P) content of shoot with MR + PI + LPGPR1 by 1.2 and 1.5 fold, respectively over MR alone treatment. On the basis of overall mean, MR + PI + LPGPR1 significantly improved the yield by 8.2 % over Mesorhizobium alone application. It seems from foregoing study that tripartite combination of different micro-organisms can be explored as biofertilizer for improvement in chickpea productivity. PMID- 26261404 TI - L-Dopa production and antioxidant activity in Hybanthus enneaspermus (L.) F. Muell regeneration. AB - Hybanthus enneaspermus is an ethanobotanical plant extensively used in Indian traditional medicine. Quick and efficient in vitro mass propagation of this plant species was established for commercial utilization from leaf and node explants using various concentrations and combinations of plant growth regulators and polyamines. The maximum number of multiple shoots per leaf explant (40 shoots) was achieved on MS medium supplemented with 20 mg/l spermidine in combination with 4 mg/l BA+1.5 mg/l IAA after 8 weeks of culture. The elongated shoots were rooted (16 roots/shoot) on MS medium with the best concentration of IBA (1.5 mg/l) and in combination with 20 mg/l putrescine after 5 weeks of culture. The plants were successfully acclimatized (98 %) in the sand: soil: vermiculite mixture (1:1:1 v/v/v) in the greenhouse. An increased antioxidant activity was recorded in vitro regenerated shoots when compared to in vitro-induced roots. L Dopa content was recorded higher in leaves (8.31 mg/g DW) followed by stem (6.22 mg/g DW) and root (3.22 mg/g DW) of leaf-derived plants than the field-grown parent plant after 5 weeks. By adopting this protocol, the regenerated-plants could be used for drug production and pharmacology work with as an alternative to field-grown plants. PMID- 26261405 TI - A high-frequency in vitro multiplication, micromorphological studies and ex vitro rooting of Cadaba fruticosa (L.) Druce (Bahuguni): a multipurpose endangered medicinal shrub. AB - An efficient and reproducible in vitro propagation protocol has been established for Cadaba fruticosa (L.) Druce. Surface-sterilized nodal stem segments of mature plant were used as explants for culture establishment. Multiple shoots were optimally differentiated from the nodal stem explants through bud breaking on Murashige and Skoog (1962) medium containing 3.0 mg l(-1) benzyladenine (BA). The effect of different plant growth regulators and minerals were studied on different stages of micropropagation procedure (i.e., explant establishment, shoot multiplication/growth and ex vitro rooting). Additionally, for enhancing shoot multiplication during subculture, MS medium was modified (MMS) with higher levels of magnesium, potassium and sulphate ions. Out of these, MMS3 medium containing 0.25 mg l(-1) each of BA and Kin (N6-furfuryladenine), with 0.1 mg l( 1) NAA (alpha-naphthalene acetic acid) was found the best for shoot multiplication (42.45 +/- 3.82 per culture vessel). The in vitro regenerated shoots were rooted under ex vitro conditions on treating the shoot base with 500 mg l(-1) of IBA (indole-3 butyric acid) for 3 min on sterile Soilrite(r). The ex vitro rooted plants were hardened in the greenhouse and transferred to the field with ~85 % survival rate. There were not any visual differences between wild and micropropagated plants in the field, although the later underwent significant changes during acclimatization. Micromorphological changes on leaf surface characters from in vitro to acclimatized plantlets were studied in terms of development of glandular trichomes, changes in vein spacing and vein structure in order to understand the nature of plant responses towards environmental conditions. The method developed and defined can be applied for commercial cultivation, which may be important for extraction of bioactive compounds and may facilitate conservation of this multipurpose endangered medicinal shrub. PMID- 26261406 TI - An efficient in vitro shoot regeneration from leaf petiolar explants and ex vitro rooting of Bixa orellana L.- A dye yielding plant. AB - Bixa orellana L. (Bixaceae) is a multipurpose tree grown for the production of commercially important dyes. In the present study, an efficient, reproducible protocol was developed for direct plant regeneration from in vitro derived petiole explants of Bixa orellana L. Murashige and Skoog medium (MS) supplemented with 2-isopentenyl adenine (9.8 MUM) and naphthalene acetic acid (10.7 MUM) was found to be optimum for production of high frequency of shoot organogenesis. Subculturing of the shoots onto the fresh MS medium containing similar concentrations of 2-iP (9.8 MUM) and NAA (10.7 MUM) produced elongated shoots. Elongated shoots when placed onto MS medium supplemented with 1.7 MUM indole-3 acetic acid and 14.7 MUM 2-iP produced optimal rooting. Rooted plantlets were acclimatized and transplanted to the field successfully. Histological investigation revealed the origin of shoot primordia, from sub-epidermal cells of petiole explants. The regeneration protocol developed in this study can be useful for mass in vitro propagation and effective genetic transformation of commercially important edible dye yielding tree species. PMID- 26261407 TI - Efficient micropropagation and assessment of genetic fidelity of Boerhaavia diffusa L- High trade medicinal plant. AB - Boerhaavia diffusa L is a medicinal herb with immense pharmaceutical significance. The plant is used by many herbalist, Ayurvedic and pharmaceutical industries for production biopharmaceuticals. It is among the 46 medicinal plant species in high trade sourced mainly from wastelands and generally found in temperate regions of the world. However, the commercial bulk of this plant shows genetic variations which are the main constraint to use this plant as medicinal ingredient and to obtain high value products of pharmaceutical interest from this plant. In this study, we have regenerated the plant of Boerhaavia diffusa L through nodal explants and evaluated genetic fidelity of the micropropagated plants of Boerhaavia diffusa L with the help of random amplified polymorphic DNA (RAPD) markers. The results obtained using RAPD showed monomorphic banding pattern revealing genetic stability among the mother plant and in vitro regenerated plants of Boerhaavia diffusa L. PMID- 26261408 TI - In vitro propagation and conservation of Satureja avromanica Maroofi-an indigenous threatened medicinal plant of Iran. AB - An efficient and rapid in vitro propagation system for Satureja avromanica, a rare and endangered folk medicinal plant of Iran was developed through the shoot tip and leaf disc explants. Nodal and leaf explants from wild plants were established on MS and WPM media supplemented with BA, BAP and TDZ (0, 0.1, 0.5, 1, 1.5, 2, 5 and 10 mgl(-1)) alone or by application of BA and TDZ (0, 2, 5 and 10 mgl(-1)) in combination with IBA and 2,4-D (0, 0.1, 0.5 and 1 mgl(-1)), respectively. Based on results, the highest mean shoot number (6.21) was obtained on MS medium supplemented with 2 mgl(-1) BA. Regarding the shoot elongation, MS supplemented with 2 mgl(-1) TDZ and MS containing 5 mgl(-1) BA showed the longest shoots (4.82 and 4.39 cm, respectively) after 6 weeks of culture. As a matter of fact, increasing all three tested cytokinins levels led to enhancement of explant response frequency and regenerated shoot number. On the other side, WPM medium supplemented with 0.1 mgl(-1) IBA was found suitable for rooting of regenerated shoots. RAPD molecular analysis revealed genetic stability of in vitro raised plants. In conclusion, individual application of BA, BAP and TDZ were in favor of S. avromanica direct shoot regeneration while treatment media with a combination of IBA and BA as well as 2,4-D and TDZ resulted in callogenesis in most explants. Finally, the in vitro raised plantlets were acclimatized and successfully established in the greenhouse conditions. Our developed protocol can be employed for the large-scale micropropagation and conservation of S. avromanica as a threatened medicinal plant. PMID- 26261409 TI - Micropropagation and assessment of genetic fidelity of Henckelia incana: an endemic and medicinal Gesneriad of South India. AB - Henckelia incana is an endemic medicinal plant used for the treatment of fever and skin allergy. In the present study shoot regeneration was evaluated on Murashige and Skoog's (MS) medium supplemented with auxins, Indole-3-acetic acid (IAA), Indole-3- butyric acid (IBA), 1-Naphthaleneacetic acid (NAA), 2, 4 Dichlorophenoxyacetic acid (2, 4-D) and cytokinins, 6-Benzylaminopurine (BAP) and Kinetin (Kn) at concentrations of 0.5, 1.0, 2.0, 3.0, 4.0 and 5.0 mgl(-1). MS medium with IBA (18.08), NAA (17.83) and IAA (17.58) at 0.5 mgl(-1) concentrations showed efficient regeneration. Regenerated shoots were rooted on half-strength MS medium with and without 0.5 mgl(-1) IBA or NAA. The plantlets were successfully hardened in rooting trays (peat, vermiculite and sand) and transferred to field mileu. The genetic fidelity of in vitro raised plants was assessed by using three different single primer amplification reaction (SPAR) markers namely random amplified polymorphic DNA (RAPD), inter-simple sequence repeat (ISSR) and direct amplification of mini-satellite DNA region (DAMD). The results consistently demonstrated true-to-true type propagation. This is the first report of in vitro propagation and establishment of true-to-true type genetic fidelity in H. incana. PMID- 26261410 TI - Gluten characteristics imparting bread quality in wheats differing for high molecular weight glutenin subunits at Glu D1 locus. AB - High yielding genotypes differing for high molecular weight glutenin subunits at Glu D1 locus in national wheat programme of India were examined for bread loaf volume, gluten and protein contents, gluten strength, gluten index and protein gluten ratio. Number of superior bread quality genotypes in four agro climatically diverse zones of Indian plains was comparable in both categories of wheat i.e., 5 + 10 and 2 + 12. There wasn't any difference in average bread loaf volume and grain protein content either. 5 + 10 wheats showed better gluten strength and their gluten quality was also superior in the zones where protein content was high. 2 + 10 wheats exerted more gluten due to better protein-gluten ratio. Good bread making in 5 + 10 was derived by better gluten strength and also gluten quality in certain regions but bread quality in 2 + 12 wheats was channelized through higher gluten content as they were more efficient in extracting gluten from per unit protein. Difference in route to bread quality was apparent as gluten content and gluten strength were the key gluten attributes in 5 + 10 whereas protein content and gluten index were prominent in 2 + 12 types. Unlike 2 + 12, there was a ceiling in gluten harvest of 5 + 10 wheats as higher protein failed to deliver more gluten after some limit. PMID- 26261411 TI - Arsenite and arsenate impact the oxidative status and antioxidant responses in Ocimum tenuiflorum L. AB - Biochemical responses of Ocimum tenuiflorum plants were studied upon exposure to arsenite (AsIII) and arsenate (AsV) for 1 to 10 d. Plants accumulated significant amounts of As in leaves (662 MUg g(-1) dry weight; DW and 412 MUg g(-1) DW in response to 100 MUM AsIII and AsV exposure, respectively after 10 d). Consequently, fresh weight and growth of plants declined in a concentration dependent manner. Further, total chlorophyll and carotenoid contents also declined while oxidative stress markers increased, particularly on longer durations. Various antioxidant enzymes and thiols (cysteine and glutathione; GSH) showed significant and variable increases upon exposure to AsV and AsIII with the response being comparatively better in response to AsV. Proline increased significantly upon exposure to both AsIII and AsV. Plants thus tolerated high As concentrations through induced antioxidant machinery. PMID- 26261412 TI - Comparative expression analysis of senescence gene CsNAP and B-class floral development gene CsAP3 during different stages of flower development in Saffron (Crocus sativus L.). AB - Crocus sativus, a monocot triploid species belonging to the Iridaceae family, is cultivated for its red stigmatic lobes of the carpel that constitute saffron. Flower development has been extensively studied in different plants. Different floral developmental pathways have been deciphered in many plants. In Crocus sativus, flower is the most important part and understanding the pathway underlying the flower development can pave the way for new avenues to improve its productivity and quality. The combination of class A genes (including APETALA1; CsAP1 and APETALA2; CsAP2), class B genes (including APETALA3; CsAP3 and PISTILLATA; CsPI) and class C genes (including AGAMOUS; CsAG) that are active in each whorl, determines the identity of the organs that will later develop in that whorl. CsAP3 is a class B homeotic gene which promotes petal and stamen formation and has a very important role in flower development. It also activates other genes playing pivotal role in flower development. It has been earlier reported that CsAP3 gene has direct role in activation of CsNAP gene which promotes senescence in plants. Present work was focused on study of relative gene expression changes of CsAP3 and CsNAP gene during different stages of flower development. CsAP3 gene expression was found maximum during late-preanthesis stages of stigma development. Expression increases from stage 5 to stage 6 of flower development and then reduces again from stage 6 to stage 7. CsNAP gene had moderate expression during stage 3 to stage 4 transition and its expression increased abruptly from stage 6 to stage 7 of flower development. There is no direct concordance in the expression of CsAP3 and CsNAP gene expression in saffron. We may conclude that some other factor(s) may be responsible for initiation of CsNAP expression and CsAP3 gene may directly/indirectly be involved in regulating the factors responsible for CsNAP activation. PMID- 26261413 TI - Reduced macular function in ABCA4 carriers. AB - PURPOSE: To study retinal function and morphology in ABCA4 carriers to investigate if ABCA4 carriership is associated with any functional or morphological changes and, if so, to explore whether certain mutations may be associated with particularly severe alterations. METHODS: Eighteen subjects were recruited by means of being the parents of 10 teenagers/young adults with genetically confirmed ABCA4-associated retinal degenerations. The teenagers/young adults are well-known patients and have been followed in our clinic for many years. The eighteen subjects underwent careful ophthalmological examinations, including fundus photography and autofluorescence imaging, Goldmann perimetry, optical coherence tomography (OCT), full-field electroretinography (ffERG), multifocal electroretinography (mERG), and ABCA4 gene sequencing. The ffERG and mERG results were compared with those of healthy controls. RESULTS: All subjects carried at least one ABCA4 mutation. Two subjects were compound heterozygous and therefore were excluded from the group-wise statistical analysis. Thirteen different ABCA4 mutations were found. C.2894 A>G (5/18) and c.768 G>T (4/18) were most common. Fourteen of 16 ABCA4 carriers demonstrated significantly altered mERG parameters (reduced amplitudes and/or delayed implicit times (ITs)) compared to normal values. In addition, the two subjects with compound heterozygous ABCA4 mutations had altered mERG parameters. A statistical comparison to the control group showed significantly reduced amplitudes and delayed ITs; p<=0.003 for all mERG parameters. FfERG parameters were altered in two ABCA4 carriers and one of the subjects with compound heterozygous ABCA4 mutations (reduced amplitude and delayed IT for the 30 Hz flicker ERG). No significant alterations were found for the whole group of ABCA4 carriers compared to the ffERG control group. Fundus photographs showed subtle to extensive pigmentary changes in several ABCA4 carriers. CONCLUSIONS: In this study, ABCA4 carriers demonstrated reduced macular function measured by mERG along with none to subtle and even extensive morphological retinal changes. The c.768 G>T, c.5461-10T>C, and c.319 C>T mutations were associated with the most deviant ERGs, including both significant reduction of mERG amplitudes and prolongation of mERG ITs, as well as with reduced amplitude or delayed IT for the 30 Hz flicker ffERG in a few cases. They may therefore be considered serious mutations. The c.5917delG and c.4469 G>A mutations were associated with milder or no macular alteration. Long-term follow up of these and other ABCA4 carriers may be of importance to elucidate the role of ABCA4 mutations in age-related macular degeneration. Moreover, improved knowledge of separate ABCA4 mutations may help us to better understand their role in ABCA4-associated retinal degenerations. PMID- 26261414 TI - Nonsyndromic retinitis pigmentosa is highly prevalent in the Jerusalem region with a high frequency of founder mutations. AB - PURPOSE: Nonsyndromic retinitis pigmentosa (RP) is the most common inherited retinal degeneration, and prevalence of the disease has been reported in populations of American and European origin with a relatively low consanguinity rate. Our aim was to determine the prevalence of nonsyndromic RP in the Jerusalem region, which has a population of about 1 million individuals with a high rate of consanguinity. METHODS: The patients' clinical data included eye exam findings (visual acuity, anterior segment, and funduscopy) as well as electroretinographic (ERG) testing results under scotopic and photopic conditions. Mutation analysis on a subgroup of patients was performed mainly with candidate gene analysis and homozygosity mapping. RESULTS: We evaluated the medical records of patients with degenerative retinal diseases residing in the Jerusalem region who were examined over the past 20 years in a large tertiary medical center. A total of 453 individuals affected with nonsyndromic RP were diagnosed at our center, according to funduscopic findings and ERG testing. Based on the estimated population size of 945,000 individuals who reside in the vicinity of Jerusalem, the prevalence of nonsyndromic RP in this region is 1:2,086. The prevalence of RP was higher among Arab Muslims (1:1,798) compared to Jews (1:2,230), mainly due to consanguineous marriages that are more common in the Arab Muslim population. To identify the genetic causes of RP in our cohort, we recruited 383 patients from 183 different families for genetic analysis: 70 with autosomal recessive (AR) inheritance, 15 with autosomal dominant, 86 isolate cases, and 12 with an X-linked inheritance pattern. In 64 (35%) of the families, we identified the genetic cause of the disease, and we revised the inheritance pattern of 20 isolate cases to the AR pattern; 49% of the families in our cohort had AR inheritance. Interestingly, in 42 (66%) of the genetically identified families, the cause of disease was a founder mutation. CONCLUSIONS: Previous studies showed an approximate prevalence of 1:5,260 on average for nonsyndromic RP in American and European populations. We show that the prevalence in the vicinity of Jerusalem is two-and-a-half times higher due to a high rate of consanguinity and highly prevalent founder mutations within the historically semi-isolated subpopulations we serve. PMID- 26261415 TI - Comparing consistency of clear corneal incisions using a traditional diamond keratome and a newly designed diamond keratome. AB - PURPOSE: To compare the consistency of incision architecture utilizing a traditional diamond keratome and a newly designed diamond keratome. METHODS: We used a traditional diamond keratome and newly designed diamond keratome to create clear corneal incisions in human cadaveric donor eyes. Three surgeons with varying levels of experience made 30 incisions with each keratome; and the wound architecture was measured including incision lengths, epithelial and endothelial widths, and the central epithelial incision's deviation from a straight line entrance. RESULTS: The mean absolute difference in right and left incision lengths (traditional: 0.182 +/- 0.158 mm and new 0.088+/-0.077 mm [P<0.003]), mean absolute difference in epithelial and endothelial incision width (traditional: 0.181+/-0.144 mm and new 0.080+/-0.092 mm [P<0.002]), endothelial incision central deviation from a straight line (traditional: 0.128+/-0.242 mm and new -0.046+/-0.124 mm [P<0.001]) were all significantly more consistent with the newly designed diamond keratome than with the traditional diamond keratome. CONCLUSION: The newly designed diamond keratome creates a more consistent clear corneal incision than a traditional diamond keratome across a variety of surgical skill levels and does not require advanced levels of training to achieve this consistency. PMID- 26261416 TI - Small molecules against B-RAF (BRAF) Val600Glu (V600E) single mutation. PMID- 26261417 TI - Magnetic removal of Entamoeba cysts from water using chitosan oligosaccharide coated iron oxide nanoparticles. AB - Amebiasis, a major health problem in developing countries, is the second most common cause of death due to parasitic infection. Amebiasis is usually transmitted by the ingestion of Entamoeba histolytica cysts through oral-fecal route. Herein, we report on the use of chitosan oligosaccharide-functionalized iron oxide nanoparticles for efficient capture and removal of pathogenic protozoan cysts under the influence of an external magnetic field. These nanoparticles were synthesized through a chemical synthesis process. The synthesized particles were characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and zeta potential analysis. The particles were found to be well dispersed and uniform in size. The capture and removal of pathogenic cysts were demonstrated by fluorescent microscopy, transmission electron microscopy, and scanning electron microscopy (SEM). Three-dimensional modeling of various biochemical components of cyst walls, and thereafter, flexible docking studies demonstrate the probable interaction mechanism of nanoparticles with various components of E. histolytica cyst walls. Results of the present study suggest that E. histolytica cysts can be efficiently captured and removed from contaminated aqueous systems through the application of synthesized nanoparticles. PMID- 26261418 TI - Nanoemulsions as novel oral carriers of stiripentol: insights into the protective effect and absorption enhancement. AB - Oral administration remains a significant challenge in regards to drugs with serious solubility and stability issues. This article aimed to investigate the suitability of nanoemulsions as oral carriers of stiripentol (STP), an acid labile drug, for enhancement of stability and bioavailability. STP-loaded nanoemulsions (STP-NEs) were prepared by using a solvent diffusion/ultrasonication technique. STP-NEs were characterized in a variety of ways such as by particle size, entrapment efficiency, in vitro drug release, and transmission electron microscopy. A bioavailability study was performed in rats after oral administration of either STP-NEs, or commercial formulation (Diacomit). The resultant nanoemulsions were 146.6 nm in particle size with an entrapment efficiency of 99.47%. It was demonstrated that nanoemulsions significantly improved the biochemical stability and bioavailability of STP. The bioavailability of STP-NEs was up to 206.2% relative to Diacomit. Nanoemulsions fabricated from poly(ethylene glycol) monooleate/medium-chain triglycerides exhibited excellent performance in drug stabilization and absorption enhancement. The results suggest that STP-NEs are a promising means to solve the problems associated with stability and solubility of STP. PMID- 26261419 TI - A family-oriented treatment program for youths with ketamine abuse and their caregivers: a pilot study in Taiwan. AB - OBJECTIVE: The abuse of ketamine by youths has grown into a serious public health issue. However, a reliable and efficient treatment has still not been found for youths who abuse ketamine. This pilot study investigated the effects of a family oriented treatment program for ketamine-using youths and their caregivers. METHODS: To carry out this study, 42 youths with ketamine use (mean age 16.6+/ 1.1 years) who were referred to take part in a 10-week treatment program based on motivational enhancement principles were selected, as were their principal caregivers (mean age 46.4+/-7.1 years), who were similarly referred to take part in a 10-week training program for parenting skills. The study had the youths complete the Chinese Craving Beliefs Questionnaire, the Adolescents' Behavior problem Scale, and the Family APGAR both immediately before and after the program. Likewise, the youths' caregivers completed the Family APGAR, the 12-item version of the Chinese Health Questionnaire, and the Parenting Stress Index. RESULTS: Of the 42 youth-caregiver pairs that took part in this study, 37 (88%) completed the 10-week program and both sets of assessments. After the treatment, the participating youths' substance cravings declined (t=3.88, P<0.001), while family function, as perceived by the participating caregivers, significantly increased (t=2.22, P=0.033). The improvement in caregivers' perceptions of family function were positively related to the improvement of the caregivers' health status (r=-0.36, P=0.022). CONCLUSION: According to its results, this pilot study submits that family-oriented treatment programs may be considered a potentially effective treatment option for youths who abuse ketamine. Additional studies with larger sample sizes, as well as longer follow-up periods, are necessary to verify whether this type of treatment also prevents youths using ketamine from relapsing. PMID- 26261420 TI - Whole blood defensin mRNA expression is a predictive biomarker of docetaxel response in castration-resistant prostate cancer. AB - This study tested the potential of circulating RNA-based signals as predictive biomarkers for docetaxel response in patients with metastatic castration resistant prostate cancer (CRPC). RNA was analyzed in blood from six CRPC patients by whole-transcriptome sequencing (total RNA-sequencing) before and after docetaxel treatment using the Illumina's HiSeq platform. Targeted RNA capture and sequencing was performed in an independent cohort of ten patients with CRPC matching the discovery cohort to confirm differential expression of the genes. Response to docetaxel was defined on the basis of prostate-specific antigen levels and imaging criteria. Two-way analysis of variance was used to compare differential gene expression in patients classified as responders versus nonresponders before and after docetaxel treatment. Thirty-four genes with two fold differentially expressed transcripts in responders versus nonresponders were selected from total RNA-sequencing for further validation. Targeted RNA capture and sequencing showed that 13/34 genes were differentially expressed in responders. Alpha defensin genes DEFA1, DEFA1B, and DEFA3 exhibited significantly higher expression in responder patients compared with nonresponder patients before administration of chemotherapy (fold change >2.5). In addition, post docetaxel treatment significantly increased transcript levels of these defensin genes in responders (fold change >2.8). Our results reveal that patients with higher defensin RNA transcripts in blood respond well to docetaxel therapy. We suggest that monitoring DEFA1, DEFA1B, and DEFA3 RNA transcripts in blood prior to treatment will be helpful to determine which patients are better candidates to receive docetaxel chemotherapy. PMID- 26261421 TI - Low claudin-6 expression correlates with poor prognosis in patients with non small cell lung cancer. AB - OBJECTIVE: Claudins are found in junctional complexes mediating cell adhesion and are involved in the attachment of tight junctions to the underlying cytoskeleton. Abnormal claudin-6 expression has been observed for a variety of malignant solid tumors, but the expression of claudin-6 in non-small cell lung cancer (NSCLC) has not yet been characterized. METHODS: Immunohistochemistry, reverse transcription polymerase chain reaction (RT-PCR), and western blot analysis were used to quantify claudin-6 expression in 123 cases of NSCLC and non-cancerous adjacent tissue. We analyzed the relationship between claudin-6 expression and clinicopathological features of NSCLC. The Kaplan-Meier method was used to analyze postoperative survival rates, and the log-rank test was used to assess differences in survival rates. The Cox regression model was used to perform multivariate analysis. RESULTS: Claudin-6 expression was low for 61 of 123 (49.6%) NSCLC tissue samples and for 33 of 123 (26.8%) normal adjacent tissue samples. RT-PCR and western blot analyses confirmed the immunohistochemistry results. Claudin-6 expression was associated with lymph node metastasis (P<0.001) and TNM stage (P=0.007). Kaplan-Meier analysis indicated that patients with low claudin-6 expression had significantly lower survival rates than those with high claudin-6 expression. Multivariate analysis suggested that low claudin-6 expression was an independent indicator of prognosis in NSCLC patients. CONCLUSION: Low claudin-6 expression is an independent prognostic biomarker that indicates a worse prognosis in patients with NSCLC. PMID- 26261422 TI - Prevalence and resistance pattern of Moraxella catarrhalis in community-acquired lower respiratory tract infections. AB - INTRODUCTION: Moraxella catarrhalis previously considered as commensal of upper respiratory tract has gained importance as a pathogen responsible for respiratory tract infections. Its beta-lactamase-producing ability draws even more attention toward its varying patterns of resistance. METHODS: This was an observational study conducted to evaluate the prevalence and resistance pattern of M. catarrhalis. Patients aged 20-80 years admitted in the Department of Chest Medicine of Liaquat National Hospital from March 2012 to December 2012 were included in the study. Respiratory samples of sputum, tracheal secretions, and bronchoalveolar lavage were included, and their cultures were followed. RESULTS: Out of 110 respiratory samples, 22 showed positive cultures for M. catarrhalis in which 14 were males and eight were females. Ten samples out of 22 showed resistance to clarithromycin, and 13 samples out of 22 displayed resistance to erythromycin, whereas 13 showed resistance to levofloxacin. Hence, 45% of the cultures showed resistance to macrolides so far and 59% showed resistance to quinolones. CONCLUSION: Our study shows that in our environment, M. catarrhalis may be resistant to macrolides and quinolones; hence, these should not be recommended as an alternative treatment in community-acquired lower respiratory tract infections caused by M. catarrhalis. However, a study of larger sample size should be conducted to determine if the recommendations are required to be changed. PMID- 26261423 TI - Atrial fibrillation in Sub-Saharan Africa: epidemiology, unmet needs, and treatment options. AB - Health care in Sub-Saharan Africa is being challenged by a double burden of disease as lifestyle diseases common in the developed world, such as stroke and atrial fibrillation (AF), increase, while, simultaneously, health issues of the developing world in terms of communicable disease persist. The prevalence of AF is lower in Africa than in the developed world but is expected to increase significantly over the next few decades. Patients with AF in Africa tend to be younger and have a higher prevalence of rheumatic valvular heart disease than patients with AF in other regions. Permanent AF is the most prevalent type of AF in Africa, possibly due to the lower use of rhythm control strategies than in the developed world. Mortality rates of patients with AF in Africa are high, due largely to poor health care access and suboptimal therapy. The risk of stroke in AF, which is moderate to high in Africans as in the developed world, contributes to the high mortality rate. Patients with AF in Africa are often undertreated with antithrombotics, as cost and access to monitoring are major barriers. Vitamin K antagonists, including warfarin, are the most commonly available oral anticoagulants, but regular monitoring can be challenging, especially for patients in remote areas. Several non-vitamin K antagonist oral anticoagulants (NOACs) have been approved for use in countries across Sub-Saharan Africa and have the potential to reduce stroke burden. The higher cost of newer agents may be offset by the reduced need for regular monitoring, fixed dosing, and lower risk of intracranial bleeding; NOACs could provide a treatment option for patients in remote areas with limited access to regular monitoring. However, NOACs are not indicated in valvular AF. More work is needed to increase understanding of the epidemiology of AF and stroke, as well as to improve management strategies to reduce the burden of cardiovascular disease predicted for Africa. PMID- 26261424 TI - Anterior cruciate ligament tears treated with percutaneous injection of autologous bone marrow nucleated cells: a case series. AB - INTRODUCTION: This was a prospective case series designed to investigate treatment for anterior cruciate ligament (ACL) tears using an injection of autologous bone marrow concentrate. METHODS: Consecutive adult patients presenting to a private outpatient interventional musculoskeletal and pain practice with knee pain, ACL laxity on exam, and magnetic resonance imaging (MRI) evidence of a grade 1, 2, or 3 ACL tears with less than 1 cm retraction were eligible for this study. Eligible patients were treated with an intraligamentous injection of autologous bone marrow concentrate, using fluoroscopic guidance. Pre and postprocedural sagittal MRI images of the ACLs were analyzed using ImageJ software to objectively quantify changes between pre- and posttreatment scans. Five different types of measurement of ACL pixel intensity were examined as a proxy for ligament integrity. In addition pain visual analog scale (VAS) and Lower Extremity Functional Scale (LEFS) values were recorded at baseline and at 1 month, 3 months, 6 months, and annually postinjection. Objective outcomes measured were pre- to post-MRI measurement changes, as analyzed by the ImageJ software. Subjective outcomes measured were changes in the VAS and LEFS, and a self-rated percentage improvement. RESULTS: Seven of ten patients showed improvement in at least four of five objective measures of ACL integrity in their postprocedure MRIs. In the entire study group, the mean gray value, median, raw integrated density, and modal gray value all decreased toward low-signal ACLs (P=0.01, P=0.02, P=0.002, and P=0.08), indications of improved ligament integrity. Seven of ten patients responded to the self-rated metrics follow up. The mean VAS change was a decrease of 1.7 (P=0.25), the mean LEFS change was an increase of 23.3 (P=0.03), and mean reported improvement was 86.7%. CONCLUSION: Based on this small case series, autologous bone marrow concentrate shows promise in the treatment of grade 1, 2, and possibly grade 3 ACL tears without retraction. Further investigation using a controlled study design is warranted. PMID- 26261425 TI - Relationships between craniocervical posture and pain-related disability in patients with cervico-craniofacial pain. AB - OBJECTIVES: This cross-sectional correlation study explored the relationships between craniocervical posture and pain-related disability in patients with chronic cervico-craniofacial pain (CCFP). Moreover, we investigated the test retest intrarater reliability of two craniocervical posture measurements: head posture (HP) and the sternomental distance (SMD). METHODS: Fifty-three asymptomatic subjects and 60 CCFP patients were recruited. One rater measured HP and the SMD using a cervical range of motion device and a digital caliper, respectively. The Spanish versions of the neck disability index and the craniofacial pain and disability inventory were used to assess pain-related disability (neck disability and craniofacial disability, respectively). RESULTS: We found no statistically significant correlations between craniocervical posture and pain-related disability variables (HP and neck disability [r=0.105; P>0.05]; HP and craniofacial disability [r=0.132; P>0.05]; SMD and neck disability [r=0.126; P>0.05]; SMD and craniofacial disability [r=0.195; P>0.05]). A moderate positive correlation was observed between HP and SMD for both groups (asymptomatic subjects, r=0.447; CCFP patients, r=0.52). Neck disability was strongly positively correlated with craniofacial disability (r=0.79; P<0.001). The test-retest intrarater reliability of the HP measurement was high for asymptomatic subjects and CCFP patients (intraclass correlation coefficients =0.93 and 0.81, respectively) and for SMD (intra-class correlation coefficient range between 0.76 and 0.99); the test-retest intrarater reliability remained high when evaluated 9 days later. The HP standard error of measurement range was 0.54-0.75 cm, and the minimal detectable change was 1.27-1.74 cm. The SMD standard error of measurement was 2.75-6.24 mm, and the minimal detectable change was 6.42-14.55 mm. Independent t-tests showed statistically significant differences between the asymptomatic individuals and CCFP patients for measures of craniocervical posture, but these differences were very small (mean difference =1.44 cm for HP; 6.24 mm for SMD). The effect sizes reached by these values were estimated to be small for SMD (d=0.38) and medium for HP (d=0.76). CONCLUSION: The results showed no statistically significant correlations between craniocervical posture and variables of pain-related disability, but a strong correlation between the two variables of disability was found. Our findings suggest that small differences between CCFP patients and asymptomatic subjects exist with respect to the two measurements used to assess craniocervical posture (HP and SMD), and these measures demonstrated high test-retest intrarater reliability for both CCFP patients and asymptomatic subjects. PMID- 26261427 TI - Knowledge, attitudes, and practices regarding cervical cancer and screening among Ethiopian health care workers. AB - BACKGROUND: Though cervical cancer incidence has dramatically decreased in resource rich regions due to the implementation of universal screening programs, it remains one of the most common cancers affecting women worldwide and has one of the highest mortality rates. The vast majority of cervical cancer-related deaths are among women that have never been screened. Prior to implementation of a screening program in Addis Ababa University-affiliated hospitals in Ethiopia, a survey was conducted to assess knowledge of cervical cancer etiology, risk factors, and screening, as well as attitudes and practices regarding cervical cancer screening among women's health care providers. METHODS: Between February and March 2012 an anonymous, self-administered survey to assess knowledge, attitudes, and practices related to cervical cancer and its prevention was distributed to 334 health care providers at three government hospitals in Addis Ababa, Ethiopia and three Family Guidance Association clinics in Awassa, Adama, and Bahir Dar. Data were analyzed using SPSS software and chi-square test was used to test differences in knowledge, attitudes, and practices across provider type. RESULTS: Overall knowledge surrounding cervical cancer was high, although awareness of etiology and risk factors was low among nurses and midwives. Providers had no experience performing cervical cancer screening on a routine basis with <40% having performed any type of cervical cancer screening. Reported barriers to performing screening were lack of training (52%) and resources (53%); however the majority (97%) of providers indicated cervical cancer screening is an essential part of women's health care. CONCLUSION: There is a clear need among women's health care providers for education regarding cervical cancer etiology, risk factors and for training in low-tech, low-cost screening methods. Meeting these needs and improving the infrastructure necessary to implement appropriate screening programs is essential to reduce the burden of cervical cancer in Ethiopia. PMID- 26261428 TI - Do physiological measures predict selected CrossFit((r)) benchmark performance? AB - PURPOSE: CrossFit((r)) is a new but extremely popular method of exercise training and competition that involves constantly varied functional movements performed at high intensity. Despite the popularity of this training method, the physiological determinants of CrossFit performance have not yet been reported. The purpose of this study was to determine whether physiological and/or muscle strength measures could predict performance on three common CrossFit "Workouts of the Day" (WODs). MATERIALS AND METHODS: Fourteen CrossFit Open or Regional athletes completed, on separate days, the WODs "Grace" (30 clean and jerks for time), "Fran" (three rounds of thrusters and pull-ups for 21, 15, and nine repetitions), and "Cindy" (20 minutes of rounds of five pull-ups, ten push-ups, and 15 bodyweight squats), as well as the "CrossFit Total" (1 repetition max [1RM] back squat, overhead press, and deadlift), maximal oxygen consumption (VO2max), and Wingate anaerobic power/capacity testing. RESULTS: Performance of Grace and Fran was related to whole-body strength (CrossFit Total) (r=-0.88 and -0.65, respectively) and anaerobic threshold (r=-0.61 and -0.53, respectively); however, whole-body strength was the only variable to survive the prediction regression for both of these WODs (R (2)=0.77 and 0.42, respectively). There were no significant associations or predictors for Cindy. CONCLUSION: CrossFit benchmark WOD performance cannot be predicted by VO2max, Wingate power/capacity, or either respiratory compensation or anaerobic thresholds. Of the data measured, only whole-body strength can partially explain performance on Grace and Fran, although anaerobic threshold also exhibited association with performance. Along with their typical training, CrossFit athletes should likely ensure an adequate level of strength and aerobic endurance to optimize performance on at least some benchmark WODs. PMID- 26261429 TI - Taxonomic status of the Columbia duskysnail (Truncatelloidea, Amnicolidae, Colligyrus). AB - Undescribed freshwater snails (Amnicolidae: Colligyrus) from the Mount Hood region (northwestern United States) identified as a new species (commonly known as the Columbia duskysnail) in grey literature have been provided federal protection under the "survey and manage" provisions of the Northwest Forest Plan and have been placed on conservation watch lists. However, there are no published studies of the identity of these snails aside from a molecular phylogenetic analysis which delineated a close relationship between the single sampled population and Colligyrusgreggi, which is distributed more than 750 km to the east of the Mount Hood area. Here we examine the taxonomic status of the Columbia duskysnail based on additional molecular sampling of mitochondrial DNA sequences (COI) and morphological evidence. We found that the Columbia duskysnail is not a monophyletic group and forms a strongly supported clade with Colligyrusgreggi. The COI divergence between these broadly disjunct groups (2.1%) was somewhat larger than that within Colligyrusgreggi (1.0%) but considerably less than that among the three currently recognized species of Colligyrus (8.7-12.1%). Additionally we found that the Columbia duskysnail and Colligyrusgreggi cannot be consistently differentiated by previously reported diagnostic characters (size and shape of shell spire, pigmentation of body and penis) and are closely similar in other aspects of morphology. Based on these results we conclude that the Columbia duskysnail is conspecific with Colligyrusgreggi. PMID- 26261426 TI - Complications and challenges associated with polycystic ovary syndrome: current perspectives. AB - Polycystic ovary syndrome (PCOS) represents the most common endocrine dysfunction in fertile women and it is considered a heterogeneous and multifaceted disorder, with multiple reproductive and metabolic phenotypes which differently affect the early- and long-term syndrome's risks. Women with PCOS present an adverse reproductive profile, including a high risk of pregnancy-induced hypertension, preeclampsia, and gestational diabetes mellitus. Patients with PCOS present not only a higher prevalence of classic cardiovascular risk factors, such as hypertension, dyslipidemia, and type-2 diabetes mellitus, but also of nonclassic cardiovascular risk factors, including mood disorders, such as depression and anxiety. Moreover, at the moment, clinical data on cardiovascular morbidity and mortality in women with PCOS are controversial. Finally, women with PCOS show an increased risk of endometrial cancer compared to non-PCOS healthy women, particularly during premenopausal period. Currently, we are unable to clarify if the increased PCOS early- and long-term risks are totally due to PCOS per se or mostly due to obesity, in particular visceral obesity, that characterized the majority of PCOS patients. In any case, the main endocrine and gynecological scientific societies agree to consider women with PCOS at increased risk of obstetric, cardiometabolic, oncology, and psychological complications throughout life, and it is recommended that these women be accurately assessed with periodic follow-up. PMID- 26261430 TI - A new species of Zachaeus C.L. Koch from Turkey (Opiliones, Phalangiidae). AB - A new species of harvestmen, Zachaeusseyyari sp. n. (Opiliones, Phalangiidae), is described and illustrated on the basis of both sexes from Sirnak Province in Turkey. Differences between the new species and related species are indicated. Photographs of its characteristic structures are also provided. PMID- 26261431 TI - Five new species of Phintella Strand, 1906 (Araneae, Salticidae) from the Wuling Mountains, China. AB - Five new species of Phintella are described from the Wuling Mountains, China: Phintellaarcuata sp. n. (male and female), Phintellalevii sp. n. (female), Phintellapanda sp. n. (female), Phintellapulcherrima sp. n. (male and female), and Phintellawulingensis sp. n. (female). Distribution data, detailed morphological characteristics, and illustrations of body and genital organs are presented. PMID- 26261432 TI - Pushing the limits - two new species of Pteromalus (Hymenoptera, Chalcidoidea, Pteromalidae) from Central Europe with remarkable morphology. AB - Two new species, Pteromalusbriani sp. n. and Pteromalusjanstai sp. n., with unusual characters are described from the Central Plateau and the Alps in Switzerland, respectively. Pteromalusbriani sp. n. is remarkable in that it has the metatibia quite abruptly expanded before the middle. This type of modification of the hind tibia is unique within the Pteromalidae and probably also the entire Chalcidoidea. It is also very rare in other parasitic wasps, where it is suspected to be associated with pheromone glands. The species is a gregarious endoparasitoid of pupae of Vanessaatalanta (Linnaeus) and Aglaisurticae (Linnaeus), two common butterflies (Lepidoptera: Nymphalidae) in Europe. It is furthermore a koinobiont parasitoid ovipositing in an early larval stage of the host. The other species, Pteromalusjanstai sp. n., shows a flattened mesosoma. A dorsoventrally depressed body is a unique feature within the genus Pteromalus, but known from a number species in unrelated genera and subfamilies. The two records demonstrate that it is possible to discover entirely new species with extraordinary characters even in one of the taxonomically most thoroughly explored parts of the world. PMID- 26261433 TI - A new species of nectar-feeding bat, genus Lonchophylla, from the Caatinga of Brazil (Chiroptera, Phyllostomidae). AB - We describe Lonchophyllainexpectata sp. n. from the Caatinga of Brazil. This new species can be distinguished from all known species of Lonchophylla that occur in Brazil by dental traits, cranial size, and fur colour. Specimens of Lonchophyllainexpectata have been misidentified as Lonchophyllamordax; but Lonchophyllainexpectata is a pale-venter species, similar in external appearance to Lonchophylladekeyseri. We have found Lonchophyllainexpectata in the Caatinga of North-eastern Brazil; Lonchophyllamordax along the eastern border of the Caatinga and in the Atlantic Forest-Caatinga ecotone in North-eastern Brazil; and Lonchophylladekeyseri in the Cerrado of Mid-western Brazil, in the Brazilian Cerrado-Caatinga ecotone, and as far west as the Cerrado of Bolivia. PMID- 26261434 TI - Cytotaxonomy of unionid freshwater mussels (Unionoida, Unionidae) from northeastern Thailand with description of a new species. AB - Morphological and chromosomal characteristics of a number of unionid freshwater mussels were studied from northeastern Thailand. Karyotypes of eight species from seven genera (Chamberlainia, Ensidens, Hyriopsis, Physunio, Pseudodon, Scabies and Trapezoideus) were examined. Six species possess 2n = 38 karyotypes, whereas Scabiescrispata and an unidentified Scabies sp. lack three small chromosome pairs, giving a diploid number of 32. Moreover, the karyotypes of the unidentified Scabies differ from Scabiescrispata as it exhibits a telocentric chromosome pair (6m + 7sm + 2st + 1t). Most of the conchological characters also differ between the two species - adult size, colour pattern, muscle scars, pseudocardinal and lateral teeth. The name Scabiessongkramensis sp. n. is proposed for the unidentified species, and its description is included in this paper. Interestingly, seven species contain mostly bi-armed chromosomes, but only the mud-dweller in stagnant water, Ensidensingallsianus, contains predominantly five telocentric pairs. In addition, the marker chromosome characteristics of an unbalanced long arm, twisted centromere, a wider angle 180 degrees arrangement, a twisted arm and telomeric end union reported in this study are described for the first time for unionid mussels. PMID- 26261435 TI - Palaearctic species of Rhamphomyia (Pararhamphomyia) anfractuosa group (Diptera, Empididae). AB - Palaearctic species of the Rhamphomyia (Pararhamphomyia) anfractuosa group are revised. Rhamphomyia (Pararhamphomyia) biflexatasp. n., Rhamphomyia (Pararhamphomyia) lineodorsatasp. n., Rhamphomyia (Pararhamphomyia) nudiscutellatasp. n., and Rhamphomyia (Pararhamphomyia) shatalkinisp. n. (all from Russian Far East) are described and illustrated. A key to Palaearctic species of the Rhamphomyia (Pararhamphomyia) anfractuosa group is provided. PMID- 26261436 TI - An Asiatic Chironomid in Brazil: morphology, DNA barcode and bionomics. AB - In most freshwater ecosystems, aquatic insects are dominant in terms of diversity; however, there is a disproportionately low number of records of alien species when compared to other freshwater organisms. The Chironomidae is one aquatic insect family that includes some examples of alien species around the world. During a study on aquatic insects in Amazonas state (Brazil), we collected specimens of Chironomidae that are similar, at the morphological level, to Chironomuskiiensis Tokunaga and Chironomusstriatipennis Kieffer, both with distributions restricted to Asia. The objectives of this study were to provide morphological information on this Chironomus population, to investigate its identity using DNA barcoding and, to provide bionomic information about this species. Chironomus DNA barcode data were obtained from GenBank and Barcode of Life Data Systems (BOLD) and, together with our data, were analyzed using the neighbor-joining method with 1000 bootstrap replicates and the genetic distances were estimated using the Kimura-2-parameter. At the morphological level, the Brazilian population cannot be distinguished either from Chironomusstriatipennis or Chironomuskiiensis, configuring a species complex but, at the molecular level our studied population is placed in a clade together with Chironomusstriatipennis, from South Korea. Bionomic characteristics of the Brazilian Chironomus population differ from the ones of Chironomuskiiensis from Japan, the only species in this species complex with bionomic information available. The Brazilian Chironomus population has a smaller size, the double of the number of eggs and inhabits oligotrophic water, in artificial container. In the molecular analysis, populations of Chironomusstriatipennis and Chironomuskiiensis are placed in a clade, formed by two groups: Group A (which includes populations from both named species, from different Asiatic regions and our Brazilian population) and Group B (with populations of Chironomuskiiensis from Japan and South Korea). Genetic distance between the Brazilian population and specimens in Group A suggests that it was recently introduced in Brazil, and that its country of origin is probably South Korea. PMID- 26261437 TI - Patterns of taxonomic diversity among terrestrial isopods. AB - The publication of the world catalog of terrestrial isopods some ten years ago by Schmalfuss has facilitated research on isopod diversity patterns at a global scale. Furthermore, even though we still lack a comprehensive and robust phylogeny of Oniscidea, we do have some useful approaches to phylogenetic relationships among major clades which can offer additional insights into isopod evolutionary dynamics. Taxonomic diversity is one of many approaches to biodiversity and, despite its sensitiveness to biases in taxonomic practice, has proved useful in exploring diversification dynamics of various taxa. In the present work, we attempt an analysis of taxonomic diversity patterns among Oniscidea based on an updated world list of species containing 3,710 species belonging to 527 genera and 37 families (data till April 2014). The analysis explores species diversity at the genus and family level, as well as the relationships between species per genera, species per families, and genera per families. In addition, we consider the structure of isopod taxonomic system under the fractal perspective that has been proposed as a measure of a taxon's diversification. Finally, we check whether there is any phylogenetic signal behind taxonomic diversity patterns. The results can be useful in a more detailed elaboration of Oniscidea systematics. PMID- 26261438 TI - The terrestrial Isopoda (Crustacea, Oniscidea) of Rapa Nui (Easter Island), with descriptions of two new species. AB - Nine species of terrestrial isopods are reported for the Polynesian island of Rapa Nui (Easter Island) based upon museum materials and recent collections from field sampling. Most of these animals are non-native species, but two are new to science: Styloniscusmanuvaka sp. n. and Hawaiiosciarapui sp. n. Of these, the former is believed to be a Polynesian endemic as it has been recorded from Rapa Iti, Austral Islands, while the latter is identified as a Rapa Nui island endemic. Both of these new species are considered 'disturbance relicts' and appear restricted to the cave environment on Rapa Nui. A short key to all the oniscidean species presently recorded from Rapa Nui is provided. We also offered conservation and management recommendations for the two new isopod species. PMID- 26261439 TI - First record and redescription of the terrestrial isopod Hemilepistoidesmesserianus Borutzky, 1945 (Isopoda, Oniscidea) from Iran. AB - In the present study, Hemilepistoidesmesserianus Borutzky, 1945 is reported from Iran for the first time. This species is redescribed and diagnostic characters of both males and females are illustrated. This species is characterized by the tuberculation of all parts of the dorsal surface of the body and the male pleopod endopodite I with a triangular lobe at apex. A map with the distribution of species is presented. PMID- 26261440 TI - The agnarid terrestrial isopods (Isopoda, Oniscidea, Agnaridae) of the province of Qazvin, Iran, with a description of a new species. AB - Six species of terrestrial isopods from the province of Qazvin, central Iran, are recorded. Three species, Hemilepistusklugii (Brandt, 1833), Protracheoniscusehsani Kashani, 2014 and Mongoloniscuspersicus Kashani, 2014, were previously reported from the province. Hemilepistuselongatus Budde-Lund, 1885 and Protracheoniscusmajor (Dollfus, 1903) are recorded for the first time, and one species, Protracheoniscussarii sp. n., is described as new. The diagnostic characters of the new species are figured. PMID- 26261441 TI - Does temperature and oxygen affect duration of intramarsupial development and juvenile growth in the terrestrial isopod Porcellioscaber (Crustacea, Malacostraca)? AB - According to the temperature-size rule (TSR), ectotherms developing under cold conditions experience slower growth as juveniles but reach a larger size at maturity. Whether temperature alone causes this phenomenon is unknown, but oxygen limitation can play a role in the temperature-size relationship. Oxygen may become limited under warm conditions when the resulting higher metabolism creates a greater demand for oxygen, especially in larger individuals. We examined the independent effects of oxygen concentration (10% and 22% O2) and temperature (15 degrees C and 22 degrees C) on duration of ontogenic development, which takes place within the maternal brood pouch (marsupium), and juvenile growth in the terrestrial isopod common rough woodlouse (Porcellioscaber). Individuals inside the marsupium undergo the change from the aqueous to the gaseous environment. Under hypoxia, woodlice hatched from the marsupium sooner, but their subsequent growth was not affected by the level of oxygen. Marsupial development and juvenile growth were almost three times slower at low temperature, and marsupial development was longer in larger females but only in the cold treatment. These results show that temperature and oxygen are important ecological factors affecting developmental time and that the strength of the effect likely depends on the availability of oxygen in the environment. PMID- 26261442 TI - Histological studies on the marsupium of two terrestrial isopods (Crustacea, Isopoda, Oniscidea). AB - The marsupium, a brood pouch in peracarid crustaceans (Crustacea, Malacostraca) has evolved in terrestrial environment for providing nutrition and optimal conditions for embryogenesis. In the present study we give details on the histology and ultrastructure of its constituting elements such as oostegites and cotyledons. Marsupia of two different eco-morphological types of woodlice, namely the non-conglobating species Trachelipusrathkii Brandt, 1833 and the conglobating species Cylisticusconvexus De Geer, 1778 were investigated. Light microscopic (LM) studies showed some differences in the main structure of the two species' brood pouch: in Trachelipusrathkii, a 'clinger' type woodlice, the oostegites bend outwards during brood incubation as growing offspring require more space, while in Cylisticusconvexus, a 'roller' type isopod, the sternites arch into the body cavity to ensure space for developing offspring and still allowing conglobation of the gravid females. The quantitative analysis of the oostegites' cuticle proved that the outer part is about 2.5 - 3 times thicker compared to the inner part in both species. Electron microscopic (TEM) examinations show only small histological differences in the oostegites and cotyledon structure of the two species. Cellular elements and moderately electron dense fleecy precipitate are found in the hemolymph space between the two cuticles of oostegites. The cells contain PAS positive polysaccharide areas. TEM studies revealed some differences in the cotyledon ultrastructure of the two species. Cotyledons of Trachelipusrathkii consist of cells with cristate mitochondria and granular endoplasmic reticulum with cisterns. Cotyledons of Cylisticusconvexus consist of cells with densely cristate mitochondria and ribosomes attached to vesicular membrane structures. In both species cells with electron dense bodies were observed. We conclude that - besides the differences in marsupial shapes - the fine structure of the oostegites and cotyledons is hardly affected by the eco morphological type, specifically the conglobating or non-conglobating character of the studied species. PMID- 26261443 TI - Formation of the hindgut cuticular lining during embryonic development of Porcellioscaber (Crustacea, Isopoda). AB - The hindgut and foregut in terrestrial isopod crustaceans are ectodermal parts of the digestive system and are lined by cuticle, an apical extracellular matrix secreted by epithelial cells. Morphogenesis of the digestive system was reported in previous studies, but differentiation of the gut cuticle was not followed in detail. This study is focused on ultrastructural analyses of hindgut apical matrices and cuticle in selected intramarsupial developmental stages of the terrestrial isopod Porcellioscaber in comparison to adult animals to obtain data on the hindgut cuticular lining differentiation. Our results show that in late embryos of stages 16 and 18 the apical matrix in the hindgut consists of loose material overlaid by a thin intensely ruffled electron dense lamina facing the lumen. The ultrastructural resemblance to the embryonic epidermal matrices described in several arthropods suggests a common principle in chitinous matrix differentiation. The hindgut matrix in the prehatching embryo of stage 19 shows characteristics of the hindgut cuticle, specifically alignment to the apical epithelial surface and a prominent electron dense layer of epicuticle. In the preceding embryonic stage - stage 18 - an electron dense lamina, closely apposed to the apical cell membrane, is evident and is considered as the first epicuticle formation. In marsupial mancae the advanced features of the hindgut cuticle and epithelium are evident: a more prominent epicuticular layer, formation of cuticular spines and an extensive apical labyrinth. In comparison to the hindgut cuticle of adults, the hindgut cuticle of marsupial manca and in particular the electron dense epicuticular layer are much thinner and the difference between cuticle architecture in the anterior chamber and in the papillate region is not yet distinguishable. Differences from the hindgut cuticle in adults imply not fully developed structure and function of the hindgut cuticle in marsupial manca, possibly related also to different environments, as mancae develop in marsupial fluid. Bacteria, evenly distributed within the homogenous electron dense material in the hindgut lumen, were observed only in one specimen of early marsupial manca. The morphological features of gut cuticle renewal are evident in the late marsupial mancae, and are similar to those observed in the exoskeleton. PMID- 26261444 TI - Spectroscopic parameters of the cuticle and ethanol extracts of the fluorescent cave isopod Mesoniscusgraniger (Isopoda, Oniscidea). AB - The body surface of the terrestrial isopod Mesoniscusgraniger (Frivaldsky, 1863) showed blue autofluorescence under UV light (330-385 nm), using epifluorescence microscopy and also in living individuals under a UV lamp with excitation light of 365 nm. Some morphological cuticular structures expressed a more intense autofluorescence than other body parts. For this reason, only the cuticle was analyzed. The parameters of autofluorescence were investigated using spectroscopic methods (molecular spectroscopy in infrared, ultraviolet-visible, fluorescence, and X-ray fluorescence spectroscopy) in samples of two subspecies of Mesoniscusgraniger preserved in ethanol. Samples excited by UV light (from 350 to 380 nm) emitted blue light of wavelengths 419, 420, 441, 470 and 505 nm (solid phase) and 420, 435 and 463 (ethanol extract). The results showed that the autofluorescence observed from living individuals may be due to some beta carboline or coumarin derivatives, some crosslinking structures, dityrosine, or due to other compounds showing similar excitation-emission characteristics. PMID- 26261445 TI - Demography of some non-native isopods (Crustacea, Isopoda, Oniscidea) in a Mid Atlantic forest, USA. AB - Introduced species dominate the terrestrial isopod fauna in most inland habitats of North America, including urban landscapes. These non-native species are often very abundant and thus potentially play a significant role in detritus processing. We monitored isopod assemblages in an urban forest for a year to examine the relationship between surface activity and abiotic environmental factors, and to analyze reproductive characteristics that might contribute to their successful establishment. Using pitfall trap samples we recorded five species, two of which, Trachelipusrathkii and Cylisticusconvexus, were highly abundant. We determined size, sex and reproductive state of each individual. Surface activity of both species reflected variability in abiotic stress factors for isopods, such as soil moisture and soil temperature. Early spring the main trigger was soil temperature while later in the season increasing temperature and decreasing soil moisture jointly affected population dynamics. Activity significantly correlated with soil moisture. The temporal pattern of sex ratios supported the secondary sex ratio hypothesis. Males dominated the samples on the onset of the mating season in search of females. The pattern was reversed as females searched for suitable microsites for their offspring. Size independent fecundity decreased as conditions became more stressful late in the season. PMID- 26261446 TI - Effects of microclimate on behavioural and life history traits of terrestrial isopods: implications for responses to climate change. AB - The sensitivity of terrestrial isopods to changes in both temperature and moisture make them suitable models for examining possible responses of arthropod macro-decomposers to predicted climate change. Effects of changes in both temperature and relative humidity on aggregation, growth and survivorship of species of isopods contrasting in their morphological and physiological adaptations to moisture stress have been investigated in laboratory microcosms. All three traits were more sensitive to a reduction in relative humidity of 20 25% than they were to an increase in temperature of 5-6 degrees C. These results suggest that predicted changes in climate in south east England may reduce the extent to which soil animals stimulate microbial activity and hence carbon dioxide (CO2) emissions from soils in the future. This may help to mitigate the potential for a positive feedback between increased CO2 emissions from soils, and increased greenhouse effects causing an increase in soil temperatures. PMID- 26261447 TI - Personality affects defensive behaviour of Porcellioscaber (Isopoda, Oniscidea). AB - We evaluated individual behavioural patterns of isopods expressed as tonic immobility following some intrusive treatments. Common rough woodlice, Porcellioscaber, were kept individually in plastic boxes and tested for tonic immobility repeatedly. Reactivity, sensitivity (number of stimuli needed to respond), and endurance of tonic immobility (TI) according three types of treatments (touch, squeeze, drop) were evaluated. Touch was the weakest treatment and it was necessary to repeat it a number of times to obtain a response; while squeeze and drop induced TI more frequently. Nevertheless, duration of the response persisted for a longer time with the touch treatment. Within each set of the three treatment, the strongest response was the third one, regardless of treatment type. Duration of reaction was affected by the size of the woodlouse, the smallest individuals feigning death for the shortest time. Despite body size, we found a significant individual pattern of endurance of TI among tested woodlice, which was stable across treatments as well as across time (5 repetitions during a 3 week period). Porcellioscaber is one of the first species of terrestrial isopods with documented personality traits. PMID- 26261448 TI - NEIGHBOUR-IN: Image processing software for spatial analysis of animal grouping. AB - Animal grouping is a very complex process that occurs in many species, involving many individuals under the influence of different mechanisms. To investigate this process, we have created an image processing software, called NEIGHBOUR-IN, designed to analyse individuals' coordinates belonging to up to three different groups. The software also includes statistical analysis and indexes to discriminate aggregates based on spatial localisation of individuals and their neighbours. After the description of the software, the indexes computed by the software are illustrated using both artificial patterns and case studies using the spatial distribution of woodlice. The added strengths of this software and methods are also discussed. PMID- 26261449 TI - A fast GNU method to draw accurate scientific illustrations for taxonomy. AB - Nowadays only digital figures are accepted by the most important journals of taxonomy. These may be produced by scanning conventional drawings, made with high precision technical ink-pens, which normally use capillary cartridge and various line widths. Digital drawing techniques that use vector graphics, have already been described in literature to support scientists in drawing figures and plates for scientific illustrations; these techniques use many different software and hardware devices. The present work gives step-by-step instructions on how to make accurate line drawings with a new procedure that uses bitmap graphics with the GNU Image Manipulation Program (GIMP). This method is noteworthy: it is very accurate, producing detailed lines at the highest resolution; the raster lines appear as realistic ink-made drawings; it is faster than the traditional way of making illustrations; everyone can use this simple technique; this method is completely free as it does not use expensive and licensed software and it can be used with different operating systems. The method has been developed drawing figures of terrestrial isopods and some examples are here given. PMID- 26261450 TI - Predictors of smoking cessation behavior among Bangladeshi adults: findings from ITC Bangladesh survey. AB - BACKGROUND: Research findings on the predictors of smoking cessation behavior identified in Western countries may not be generalizable to smokers in the Southeast Asian countries (i.e., Bangladesh). This study examined the factors associated with smoking cessation behavior (quit attempts and smoking cessation) among a representative sample of Bangladeshi adults. METHODS: Data from Wave 1 (2009) and Wave 2 (2010) of the International Tobacco Control (ITC) Survey in Bangladesh, a face-to-face survey of adult smokers, were analysed. Households were sampled using a stratified multistage design and interviewed using a structured questionnaire. Respondents included in the study are 1,861 adult daily smokers (cigarette only or dual use of cigarette and bidi) in the Wave 1 survey who completed the Wave 2 follow up. RESULTS: Of the smokers (N = 1,861), 98 % were male, 18 % illiterate, 78 % married and 42 % were aged 40 or above; 89 % were cigarette smokers and 11 % were dual users (cigarette & bidi). Overall, 21.8 % of the baseline smokers made quit attempts (that is, making at least one quit attempt that lasted for at least 24 hours) during the 11- to 12-month interval between Waves 1 and 2 with only 4.1 % quitting successfully (that is, smokers who had stopped smoking for at least 6 months at the time of the Wave 2 survey). Significant predictors of attempts to quit included: residing areas outside Dhaka (OR = 3.41), being aged 40 or older (OR = 1.53), having a monthly income of above BDT10,000 (US$126) versus below BDT 5,000 (US$63) (OR = 1.57), intending to quit sometime in the future (OR = 1.73). Respondents not working indoors/outside the home were less likely to have made a quit attempt than those with no workplace restrictions on smoking (OR = 0.62). Predictors of successful smoking cessation included: being aged 40 or older (OR = 3.11), perceiving self-rated health as good or excellent (OR = 2.40), and an increased level of self-efficacy (OR = 1.75). Smokers who made a quit attempt not so recently (6 months ago or earlier) were less likely to quit than those who made a more recent (in last 6 months) quit attempt (OR = 0.23). CONCLUSION: Among Bangladeshi smokers, different factors were associated with quit attempt or successful cessation. Population based smoking cessation programs should take these factors into consideration in the design of smoking cessation interventions. At the same time, measures are necessary to encourage more smokers to make quit attempts. PMID- 26261451 TI - Major dietary patterns in Iranian adolescents: Isfahan Healthy Heart Program, Iran. AB - BACKGROUND: Limited information exists from the dietary pattern of children and adolescents particularly in developing countries. We aimed to detect major dietary patterns and their association with socio-demographic characteristics of Iranian adolescents. METHODS: Healthy Heart Promotion from Childhood as one of the "Isfahan Healthy Heart Program", Iran, projects was conducted in adolescents aged 11-18 years in Isfahan, Najafabad, and Arak districts, Iran, selected randomly by multistage sampling. This survey was conducted on 1992 adolescents in 2007. Dietary intake was assessed using a 50-item food frequency questionnaire in both communities. RESULTS: Four major dietary patterns labeled "prudent diet," fast food diet," "animal fat diet," and "Mediterranean diet" were identified. We found a significant inverse relationship between prudent and animal fat dietary patterns with age, prudent and Mediterranean dietary patterns with being boy. However, a positive relationship between fast food dietary pattern and age; fast food and animal fat dietary patterns with being boy were detected (all P < 0.05). While urbanization and TV watching correlated positively with the fast food diet, an inverse relationship between urbanization and animal fat and Mediterranean dietary patterns were found (all P < 0.01). The animal fat and fast food dietary patterns inversely associated with nutrition knowledge; however, Mediterranean diet had a positive relationship with it (all P < 0.05). Membership in sport team was positively related to all dietary pattern and regular physical activity associated only with prudent diet (all P < 0.05). CONCLUSION: The study suggests that socio-demographic characteristics and physical activity are related to dietary patterns in Iranian adolescents. PMID- 26261452 TI - Association between dietary salt intake and reservation of renal function in patients with mild hypertension. AB - BACKGROUND: It is now hypothesized whether restricted salt intake can be a potential precursor to renal dysfunction in mild hypertension state. We aimed to study the association between salt intake and renal function in patients with mild hypertension. METHODS: One hundred consecutive hypertensive Iranian patients (with systolic blood pressure 140-160 mmHg and/or diastolic 90-100 mmHg) who were referred to the hypertension research center, Isfahan, Iran, between 2011 and 2014 for screening of hypertension were assessed. Renal function was assessed by measuring serum creatinine (Cr) and creatinine clearance (CrCl). Daily salt intake was assessed on the basis of 24 h urinary sodium excretion. RESULTS: There was no association between the amounts of sodium intake and serum Cr concentration (r = 0.138, P = 0.174), however, an association was revealed between sodium intake and value of CrCl (r = 0.303, P = 0.003). Multivariable linear regression model showed that sodium intake could effectively predict renal function assessed by CrCl (Beta = 0.070, P = 0.016). CONCLUSION: There is an association between sodium intake and reservation of renal function in mild hypertension state and thus by restriction of dietary salt intake, reserving renal function, and preventing appearance and progression of renal insufficiency in higher degrees of hypertension can be facilitated. PMID- 26261453 TI - The effect of probiotic soy milk and soy milk on anthropometric measures and blood pressure in patients with type II diabetes mellitus: A randomized double blind clinical trial. AB - BACKGROUND: The objective of this clinical trial was to assess the effects of probiotic soy milk and soy milk on anthropometric measures and blood pressure (BP) in type 2 diabetic (T2D) patients. METHODS: A total of 40 patients with T2D, 35-68 years old, were assigned to two groups in this randomized, double-blind, controlled clinical trial. The patients in the intervention group consumed 200 ml/day of probiotic soy milk containing Lactobacillus planetarium A7 and those in control group consumed 200 ml/day of soy milk for 8 weeks. Anthropometric and BP measurements were performed according to standard protocols. For detecting within group differences paired-sample t-tests was used and analysis of covariance was used for determining any differences between two groups. (The trial has been registered in the Iranian Registry of Clinical Trials, identifier: IRCT: IRCT201405265062N8). RESULTS: In this study, we failed to find any significant changes between probiotic soy milk and soy milk in term of body mass index (26.65 +/- 0.68 vs. 26.33 +/- 0.74, P = 0.300) and waist to hip ratio (1.49 +/- 0.08 vs. 1.54 +/- 0.1, P = 0.170). Although soy milk did not have any effect on BP, probiotic soymilk significantly decreased systolic (14.7 +/- 0.48 vs. 13.05 +/- 0.16, P = 0.001) and diastolic BP (10 +/- 0.7 vs. 9.1 +/- 1, P = 0.031). CONCLUSION: In our study, probiotic soy milk in comparing with soy milk did not have any beneficial effects on anthropometric measures in these patients. We need more clinical trial for confirming the effect of probiotic foods on anthropometric measure in diabetic patients. However, probiotic soy milk decreased systolic and diastolic BP significantly. PMID- 26261454 TI - Potato consumption as high glycemic index food, blood pressure, and body mass index among Iranian adolescent girls. AB - BACKGROUND: Potato as a high glycemic index food has different effects on healthy nutritional status. In the current study, we investigated the association between potato consumption and obesity and blood pressure among adolescent girls. METHODS: This cross-sectional survey was conducted on 205 girls (11-13 years old) in 2013 who were selected by systematic cluster random sampling from schools of all regions of Isfahan, Iran. Dietary intakes were collected by 53-items food frequency questionnaire. Anthropometric measurements were done based on a standard protocol. RESULTS: Adolescents that consumed all kinds of potato more than once per week had significantly higher prevalence of overweight and obesity (prevalence of overweight and obesity was 86.7 and 13.3%; P < 0.0010 in more than once per week and less than once per week groups, respectively) as well as prevalence of abdominal obesity in more than once per week consumption group was higher than less than once per week consumption group (78.2 vs. 21.8%; P < 0.001). Potato consumption (as independent variables) increased body mass index and waist circumference (as dependent variables) in crude and adjusted regression models (P < 0.050). Mean blood pressure was not significantly different among lower and higher potato consumers. CONCLUSION: Our findings suggested a positive association between potato consumption and obesity. We did not find any association between potato consumption and blood pressure in adolescents. PMID- 26261455 TI - Comparison of soymilk and probiotic soymilk effects on serum high-density lipoprotein cholesterol and low-density lipoprotein cholesterol in diabetic Wistar rats. AB - BACKGROUND: Soy milk (SM) and its fermented products are identified as rich sources of bioactive compounds helping to manage and to reduce the risk of chronic disease. This study aimed to compare the effects of SM and probiotic SM (PSM) consumption on serum low-density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) in diabetic Wistar rats. METHODS: Probiotic SM was prepared by fermentation of the plain SM with a native strain of Lactobacillus plantarum. 20 streptozotocin-nicotinamide-induced diabetic Wistar rats were divided into two groups based on the type of administered SM (SM group and PSM group). The animals were fed with 1 ml/day of either soy or PSM for 21 days. The serum lipoprotein levels were analyzed at baseline and the end of the intervention period. RESULTS: HDL-C increased significantly in PSM group. Furthermore, this group showed more percent of change in increased HDL-C in compression with SM group (P < 0.050). Regarding LDL-C level, rats fed with SM was not significantly different from the PSM group (P < 0.050); though, this biomarker was reduced in both group. CONCLUSION: Probiotic SM could modulate blood lipoprotein levels. Thus, it may be considered in managing diabetes complications and atherosclerotic risks. PMID- 26261456 TI - Soy product consumption and association with health characteristics and dietary quality indices in Isfahan, Iran. AB - BACKGROUND: To determine the average intake of soy products and its association with socio-demographic, general and health characteristics, and dietary quality indices among the population of Isfahan, Iran. METHODS: In this descriptive cross sectional study conducted on 491 subjects in 2013-2014, grocery stores, nuts stores, chain stores, and supermarkets from different areas of Isfahan Municipality were visited. Shop owners were asked to report the amounts of soy products sales (soy nut, processed soy protein, soy milk and soy yogurt). Furthermore, a food frequency questionnaire was completed from 496 customers by an experienced nutritionist. Mean sales and intake of soy products and dietary intakes including dietary quality indices and mean adequacy ratio (MAR) as well as anthropometric and socio-demographic variables were assessed. RESULTS: Soy protein and soy yogurt are the highest [673 +/- 81 (g/month)] and lowest [420 +/- 148 (g/month)] purchased soy products, respectively. While soy nut [63 +/- 10 (g/month)] was consumed to the lowest amount, soy protein [236 +/- 39 (g/month)] was the most consumed soy product. Subjects with higher consumption of soy products were older and had higher intake of protein, vitamin C, zinc and iron, and lower intake of whole grains, legumes, and vegetables as well as greater values of MAR and dietary diversity score as well as nutrient adequacy ratio for vitamin C. CONCLUSION: Soy protein is the most purchased and consumed soy product among people living in Isfahan. More intakes of whole grains and vegetables among those with higher consumption of soy foods could define greater quantities of zinc, iron and vitamin C in the diet. Soy consumption had a reverse correlation with body mass index. PMID- 26261457 TI - Association of chemerin levels with anthropometric indexes and C-reactive protein in obese and non-obese adolescents. AB - BACKGROUND: Obesity is a low-grade chronic inflammation. This epidemic is growing in different age groups including adolescents. It is accompanied with a decrease in the age for incidence of obesity-related disorders. Chemerin, as a chemokine and stimulator of anti-inflammatory adiponectin, links immune system, adipose tissue and inflammation. It may be useful in predicting obesity in the hit phase of life. This study aims to assess serum chemerin and adiponectin in relation to the inflammation and obesity indices. METHODS: This case-control study was conducted on 82 adolescent girls, aged12-18 years. They were categorized based on the percentiles of the body mass index (BMI).Serum chemerin, adiponectin, high sensitive C-reactive protein (Hs-CRP), body fat mass and its percent, waist circumference (WC) ,hip circumference (HC) were measured; BMI and waist-to-hip ratio (WHR)were calculated. Data were analyzed by independent Student's t-test and Pearson correlation; path analysis was conducted, as well. RESULTS: We found a negative significant association between chemerin and adiponectin levels in both obese and non-obese groups(r =-0.387, P = 0.014 vs. r = 0.362, respectively, P = 0.018). Serum chemerin was higher in obese than in non-obese adolescents (441.83 +/- 47.79 vs. 409.30 +/- 66.12 ug /l, respectively, P = 0.012), whereas mean adiponectin level was lower in obese participants than in the other group (4.79 +/- 0.94 versus 5.2 +/- 0.53ug/ml, respectively, P = 0.016). Chemerin concentrations had significant positive correlation with Hs-CRP levels, BMI, WC, HC, WHR, body fat mass and its percent (P < 0.05). CONCLUSION: Chemerin concentrations were associated with and adiponectin levels in obese girl adolescents, negatively. Hs-CRP, BMI, WC, HC, WHR, body fat mass and its' percent were in positive relation with chemerin levels, and inverse association with serum adiponectin concentrations. Our findings suggest that chemerin can be considered as an early marker of the inflammatory process in obesity. PMID- 26261458 TI - Is there any association between rice consumption and some of the cardiovascular diseases risk factors? A systematic review. AB - BACKGROUND: White rice is considered as a staple food in most population in the world, and there may be an association between rice intake and cardiovascular disease (CVD) risks. The present article was reviewed the correlation between rice intake and CVD and some of its risk factors. METHODS: We searched in PubMed, Google scholar, and SCOPUS to February 2015 by using several keywords such as low and high density lipoprotein, triglyceride, total cholesterol, fasting blood glucose, CVD or risks, metabolic syndrome, diabetes, obesity, lipid profile, and refined grains or rice and white rice. Finally, 14 studies were included in our systematic review. RESULTS: There was found a positive association between white rice intake and risk factors of CVD including metabolic syndrome and type 2 diabetes. Furthermore, it seems that there is no any significant correlation between white rice consumption and incidence of CVD and its mortality. CONCLUSION: Finding from available data suggested the important roles of higher white rice consumption on CVD risk factors. PMID- 26261459 TI - The impact of HIV/AIDS on compliance with antidepressant treatment in major depressive disorder: A prospective study in a South African private healthcare cohort. AB - BACKGROUND: MDD and HIV/AIDS have a high prevalence worldwide with severe consequences for patients. In both conditions, compliance with treatment is key to successfully treat these disorders. In the current study, we examine the effect of MDD on the compliance with ADs in patients diagnosed with co-morbid HIV/AIDS and how different classes of ADs influence compliance in this group of patients. METHODS: A prospective, cohort study design was used to analyse nationally representative medicine claims data submitted to a privately-owned South African Pharmaceutical Benefit Management (PBM) company. Two groups were distinguished in the database, namely patients with only MDD and patients with both MDD and HIV/AIDS, over a six-year study period. The study population was determined by the following inclusion criteria: patients older than 18 years, MDD should be diagnosed by a psychiatrist supported by an appropriate ICD-10 code, and all patients have to be on combination antiretroviral treatment (cARV) treatment. The medicine possession ratio (MPR) was used as proxy to determine patient compliance with AD medication. RESULTS: 127 patients (i.e. 0.24%) met the criteria of co-morbid MDD and HIV/AIDS. Females have a significantly higher prevalence of MDD and HIV/AIDS when compared to males. Patients diagnosed with both HIV/AIDS and MDD (74.43. +/- 32.03, 95% Cl: 71.51-77.34) have a statistical significantly (p < 0.0001) lower compliance with AD treatment vs. MDD patients (80.94% +/- 29.44, 95% Cl: 80.56-81.33), but the practical significance thereof, is low (Cohen's d = 0.2255). In this group only 26.83% of TCA had acceptable compliance compared to the 58.57% of SNRIs. Noteworthy observations were that 75% (p < 0.0217; Cramer's V = 0.0388) of venlafaxine and 28.6% (p < 0.0197; Cramer's V = -0.0705) of the paroxetine items were compliant in patients diagnosed with both HIV/AIDS and MDD. CONCLUSIONS: AD compliance is statistical significantly lower in depressed HIV/AIDS vs. depressed non-HIV/AIDS patients. However, these differences is of low practical or clinical significance, meaning that depressed HIV/AIDS patients would have missed approximately two AD doses (6.5% of a 30-day treatment period) more than the non-HIV/AIDS depressed patient over the same treatment period. PMID- 26261461 TI - Spontaneous biloma: a case report. AB - A biloma is an encapsulated collection of bile located in the abdomen. It occurs spontaneously or secondary to traumatic or iatrogenic injury to the biliary system. The patient's medical history, symptoms and diagnostic imaging findings suggest the diagnosis, but a definitive diagnosis is provided by drainage and biochemical analysis of the fluid. We report a case of a patient admitted with acute abdominal pain in the right hypochondrium caused by a spontaneous biloma. This is a rare condition, and the reason for the onset was not identified. We discuss the role of the various diagnostic imaging techniques, particularly that of ultrasound. PMID- 26261460 TI - Altered modulation of gamma oscillation frequency by speed of visual motion in children with autism spectrum disorders. AB - BACKGROUND: Recent studies link autism spectrum disorders (ASD) with an altered balance between excitation and inhibition (E/I balance) in cortical networks. The brain oscillations in high gamma-band (50-120 Hz) are sensitive to the E/I balance and may appear useful biomarkers of certain ASD subtypes. The frequency of gamma oscillations is mediated by level of excitation of the fast-spiking inhibitory basket cells recruited by increasing strength of excitatory input. Therefore, the experimental manipulations affecting gamma frequency may throw light on inhibitory networks dysfunction in ASD. METHODS: Here, we used magnetoencephalography (MEG) to investigate modulation of visual gamma oscillation frequency by speed of drifting annular gratings (1.2, 3.6, 6.0 degrees /s) in 21 boys with ASD and 26 typically developing boys aged 7-15 years. Multitaper method was used for analysis of spectra of gamma power change upon stimulus presentation and permutation test was applied for statistical comparisons. We also assessed in our participants visual orientation discrimination thresholds, which are thought to depend on excitability of inhibitory networks in the visual cortex. RESULTS: Although frequency of the oscillatory gamma response increased with increasing velocity of visual motion in both groups of participants, the velocity effect was reduced in a substantial proportion of children with ASD. The range of velocity-related gamma frequency modulation correlated inversely with the ability to discriminate oblique line orientation in the ASD group, while no such correlation has been observed in the group of typically developing participants. CONCLUSIONS: Our findings suggest that abnormal velocity-related gamma frequency modulation in ASD may constitute a potential biomarker for reduced excitability of fast-spiking inhibitory neurons in a subset of children with ASD. PMID- 26261462 TI - Intussusception in childhood: role of sonography on diagnosis and treatment. AB - OBJECTIVE: The aim of this study was to determine the role of ultrasound in the diagnosis and treatment of pediatric patients with acute abdominal pain caused by intussusceptions. MATERIALS AND METHODS: We performed a retrospective study of all pediatric patients with acute abdominal pain caused by intussusceptions and that underwent ultrasound examination at the emergency service of the Radiology Department between November 2007 and June 2013. The role of ultrasonography in the diagnosis of intussusceptions has been assessed by comparing the echographic presumptive diagnosis with the final diagnosis of discharge. Its importance in the treatment has been assessed by determining the value of ultrasound findings in the choice of the best treatment. RESULTS: The ultrasound examination was positive in 16/18 patients with a final diagnosis of intussusception. Some sonographic findings seemed to be able to predict the opportunity to resort to non-surgical therapeutic options like hydrostatic or pneumatic reduction of the intestinal segments invaginated. In our casuistry, five children presented characteristics typical of this subgroup and underwent barium enema which provided the reduction of the intestinal segments involved. The future challenge will be to perform non-surgical ultrasound-guided reductions to avoid the exposure of the infants to ionizing radiations. CONCLUSIONS: Ultrasonography is essential not only in the diagnosis, but also it adds important elements in the therapeutic choice and could play in the future an important role in non-surgical reduction of intestinal intussusceptions in pediatric patients. PMID- 26261463 TI - Endosonography of benign myometrium cysts and cyst-like lesions. AB - INTRODUCTION: Many pathological causes are responsible for the sonographic presentation of myometrium cysts and cyst-like lesions, where the distinction between these etiologies is required. THE AIM OF THE WORK: The current work is aimed at discerning between different etiologies of myometrium cysts and cyst like lesions for an optimum management. METHODOLOGY: In the course of daily practice of gynecological transvaginal ultrasound, 66 cases of myometrium cysts and cyst-like lesions have been discerned, where all were examined with endovaginal ultrasound using a multifrequency endocavitary probe having color Doppler capability. RESULTS: Adenomyosis uteri detected in 15 cases, invasive mole in 4 cases, congested arcuate veins in 20 cases, incidental cysts in 4 cases, cystic degeneration of myoma in 3 cases, C-section scar cysts and cyst like lesions in 13 cases, interstitial ectopic pregnancy in 2 cases, incomplete abortion with congested myometrium vessels in 4 cases, and arteriovenous malformation in 1 case. The number of cases with cervical nabothian cysts was not considered since they were too frequent. CONCLUSION: Endosonography is an important tool in differentiating between the various diseases that are responsible for benign myometrium cysts and cyst-like lesions, which are all important since some of them are visualized as serious clinical situations and others turn out to be of little clinical significance. PMID- 26261464 TI - Evaluation with contrast ultrasound of the prevalence of splenic infarction in left-sided infective endocarditis. AB - PURPOSE: To prospectively evaluate the prevalence of the embolization of the spleen in patients with definite left-sided infective endocarditis (IE) using a contrast-enhanced ultrasound (CEUS). METHODS: From March 2012 through September 2013, 18 consecutive patients (9 females and 9 males, aged 21-83 years) evaluated at our hospital and with definite left-sided IE according to the revised Duke criteria were enrolled. All of the patients gave informed written consent and the study was performed in conformity with the ethical guidelines of the Declaration of Helsinki. All of the patients were submitted to a CEUS of the spleen within 10 days after the definite diagnosis of IE. For the CEUS, a blood pool second generation contrast agent and an ultrasound machine with a contrast harmonic imaging technology were used. RESULTS: The splenic CEUS showed infarctions in 11 patients (61 %) and resulted positive in the 2 patients with negative echocardiography. CONCLUSIONS: In this study, CEUS of the spleen, a repeatable and low-cost imaging technique, easily allowed the bedside detection of asymptomatic and even tiny infarctions and showed a high rate of embolization in patients with definite left-sided IE. Therefore, in the setting of IE (possible or definite), CEUS of the spleen has the potential to better define or accelerate the diagnosis itself. PMID- 26261465 TI - Characterization of a murine model of cardiorenal syndrome type 1 by high resolution Doppler sonography. AB - ABSTRACT: Cardiorenal syndrome type 1 (CRS-1) is the acute kidney disfunction caused by an acute worsening of cardiac function. CRS-1 is the consequence of renal vasoconstriction secondary to renin-angiotensin system (RAS) activation. No animal models of CRS-1 are described in literature. PURPOSE: To characterize a murine model of CRS-1 by using a high-resolution ultrasound echo-color Doppler system (VEVO2100). MATERIALS: Post-ischemic heart failure was induced by coronary artery ligation (LAD) in seven CD1 mice. Fifteen and thirty days after surgery, mice underwent cardiac and renal echo-color Doppler. Serum creatinine and plasma renin activity were measured after killing. Animals were compared to seven CD1 control mice. RESULTS: Heart failure with left ventricle dilatation (end diastolic area, p < 0.05 vs. controls) and significantly reduced ejection fraction (EF; p < 0.01 vs. controls) was evident 15 days after LAD. We measured a significant renal vasoconstriction in infarcted mice characterized by increased renal pulsatility index (PI; p < 0.05 vs. controls) associated to increased creatinine and renin levels (p < 0.05 vs. controls). CONCLUSIONS: The mice model of LAD is a good model of CRS-1 evaluable by Doppler sonography and characterized by renal vasoconstriction due to the activation of the renin-angiotensin system secondary to heart failure. PMID- 26261466 TI - The role of ultrasonography in the assessment of peri-prosthetic hip complications. AB - PURPOSE: Total hip arthroplasty (THA) is a widespread option for treating hip osteoarthritis. Peri-prosthetic complications after THA represent a common event influencing patient outcome and costs. The purpose of this paper is to report the use of ultrasonography (US) to detect peri-prosthetic complications in symptomatic patients who underwent THA. METHODS: We retrospectively reviewed the records of patients with THA who underwent imaging evaluation between January 2009 and December 2012 at two different institutions. We evaluated the presence/absence of superficial and/or deep peri-prosthetic collections as well as the presence/absence of a cutaneous sinus tract. For patients who underwent both MRI and US, a concordance correlation analysis between US and MR findings was performed. RESULTS: In the reference period, 532 symptomatic patients (mean age +/- standard deviation 74 +/- 12 years) underwent X-ray and MRI examinations for suspected peri-prosthetic complications. Among them, 111 (20.9 %) underwent also US. Overall, 108 patients underwent both US and MRI. US findings included 67 superficial collections, 48 subcutaneous fistulas, 74 deep peri-prosthetic collections. Twenty-four patients had solid, mass-like peri-prosthetic collections. In 11 patients, no peri-prosthetic complications were seen. MRI findings included 68 superficial collections, 49 subcutaneous fistulas, 79 deep peri-prosthetic collections. Twenty-four patients had solid, mass-like peri prosthetic collections. In four patients, no peri-prosthetic complications were seen. Concordance analysis between US and MRI findings showed almost perfect agreement (k >= 0.89). CONCLUSION: US is an efficient and practical imaging modality to evaluate peri-prosthetic complications in patients with THA, being almost comparable to MRI in detecting and characterizing these complications. PMID- 26261467 TI - Role of B-scan ocular ultrasound as an adjuvant for the clinical assessment of eyeball diseases: a pictorial essay. AB - We report our experience in B-mode ocular ultrasonography, focusing on its contribution when the clinical examination proves to be difficult, mainly due to the existence of intraocular opacities of the ocular fundus or diagnostic doubts. We revise the ocular ultrasound technique, its indications and contraindications, comparing to the other imaging techniques. In our experience ultrasonography revealed pathological findings which confirmed the clinical suspicion in most of cases or provide additional information. With understanding of the indications for ultrasonography and proper examination technique, one can gather a vast amount of information not possible with clinical examination alone. PMID- 26261468 TI - Dynamic ultrasound with postural change facilitated the detection of an incisional hernia in a case with negative MRI findings. AB - Incisional hernias commonly develop after abdominal surgeries with a lower incidence in patients receiving laparoscopy. Diagnosis through a non-surgical approach is usually made by computed tomography or magnetic resonance images (MRI) but both image modalities require patients to be examined in a supine position. We reported a case noticing a mass over her right lower abdomen after a laparoscopic liver segmentectomy with negative findings of hernia on MRI. A hernia sac was found by ultrasound with the patient being standing, highlighting the utility of dynamic ultrasound with postural change in investigation of incisional hernias. PMID- 26261469 TI - Ultrasound-guided aspiration and steroid injection of a posterior cruciate ligament ganglion cyst: report of a case. AB - Ganglion cysts are benign masses that originate from mucinous degeneration of the connective tissues and are quite rare when arising from the knee joint. Symptoms are often represented by pain, joint tenderness, effusion and occasional swelling with a palpable mass in the popliteal region of the knee. Percutaneous aspiration followed by a corticosteroid injection of a ganglion cyst has either a diagnostic or therapeutic meaning and its guidance through ultrasound allows the operator to make more accurate the procedure, ensuring the correct placement of the needle inside the lesion. We report our experience in the treatment of a voluminous ganglion cyst of the posterior cruciate ligament performed through the ultrasound guidance in a symptomatic young patient. PMID- 26261470 TI - Systemic mastocytosis presenting with gastrointestinal, bone and skin involvement. AB - Ultrasonography (US) is often the first imaging study performed in patient with abdominal pain or vague symptoms related to the gastrointestinal tract. To this end, it has been demonstrated that transabdominal sonography achieves good to excellent results in potential bowel disorders; especially, if ultrasonography findings are framed in the context of clinical information. Systemic mastocytosis is not a common disease and it usually involves skin, gastrointestinal tract and bone. It results from a clonal neoplastic proliferation of abnormal mast cells and clinically it can ranges from 'asymptomatic' with normal life expectancy to 'highly aggressive'. Symptoms are caused by the release of mast cells mediators, such as histamine, and by the increase bulk of mast cells in the tissue. We present herein a case of systemic mastocytosis presenting with abdominal symptomatology due to thickened colonic involvement showed by US associated with bone and skin involvement. PMID- 26261471 TI - Lymphangioma of the small bowel mesentery in a 7-year-old girl: a report of a case investigated with ultrasonography, elastosonography and computed tomography. AB - PURPOSE: To describe the characteristics of lymphangioma reporting a pediatric case of small bowel mesentery location, showing ultrasound-elastosonographic and computed tomography findings. METHODS: A 7-year-old girl suffering from vomiting and abdominal pain underwent chest-abdomen radiography and abdomen ultrasound examination at our institution. These exams were repeated for 5 days after medical therapy and a computed tomography investigation was also performed. RESULTS: Abdominal ultrasound and computed tomography examinations revealed the presence of a heterogeneous mesenteric mass occupying the right hemiabdomen displacing small bowel loops. Moreover, the mass had an irregular vascularisation pattern on color-Doppler study and appeared mostly green colored, like soft tissues, on elastosonographic colorimetric map. The little patient underwent surgery with removal of both the mass and the close adherent ileal loop. Finally, anatomopathologic diagnosis of mesenteric lymphangioma was made. CONCLUSIONS: Although mesenteric lymphangioma is a rare disease that presents neither clinical nor imaging typical features requiring invasive procedure to be diagnosed, ultrasound-elastosonographic findings can suggest a benign condition and computed tomography scan is useful in order to plan surgery. PMID- 26261472 TI - Sepsis due to pyonephrosis: an adult with pelvic-ureteric junction obstruction (PUJO) in a duplex kidney. AB - We present the case of a 75-year-old woman with sepsis. She was evaluated with bedside ultrasound with a diagnosis of pyonephrosis, and subsequently underwent a TC scan that showed a pelvic-ureteric junction obstruction (PUJO) in a duplicated renal system. PUJO associated with duplex kidney, while relatively frequent in children, is a rare condition in adults, and may lead to severe complications as in this case. PMID- 26261473 TI - Contrast sonographic appearance of sclerosing angiomatoid nodular transformation of the spleen. PMID- 26261474 TI - The value of superficial parts and endoanal ultrasonography in evaluating pilonidal disease and exclusion of perianal sepsis. AB - INTRODUCTION: Pilonidal disease is a benign anorectal inflammatory disease that involves the subcutaneous adipose tissue overlying the sacrococcygeal region. THE AIM OF THE WORK: The current study aimed to assess the value of preoperative evaluation of pilonidal disease and the exclusion of perianal sepsis using superficial parts ultrasonography and endoanal ultrasound. METHODOLOGY: Referred 30 patients were clinically diagnosed as pilonidal disease, all were examined with superficial parts ultrasonography and if the disease was extending to the perianal region further endoanal US was performed to exclude perianal sepsis. RESULTS: 7 patients showed subcutaneous abscesses and 23 patients showed pilonidal sinus tracts. Among patients with pilonidal sinus tracts, six tracts (26 %) seen as superficially situated, short narrow tracts with straight course, no side branches and with a blind end situated away from the anal canal wall. 2 (9 %) tracts showed vertical orientation and three tracts (13 %) were wide and deeply situated reaching the presacral fascia. 7 cases (30 %) showed branching pilonidal sinus tracts, two cases of them showed more than one external opening. 5 patients (22 %) showed abnormally long tracts seen reaching the perianal region. CONCLUSION: Ultrasonography is an available, inexpensive, safe imaging modality that yields a high degree of accuracy in evaluating pilonidal disease and in exclusion of perianal sepsis. PMID- 26261475 TI - Knee bursitis: a sonographic evaluation. AB - OBJECTIVE: To evaluate the use of ultrasound for the diagnosis of knee bursitis. MATERIALS AND METHODS: One-hundred and fifty-eight patients who, from May 2013 to May 2014, had an ultrasound examination of the knee and magnetic resonance imaging (MRI) of the knee during the following month were eligible for the study. The exams were reviewed by two musculoskeletal radiologists with 20 years of experience. RESULTS: Of these patients, 15 (7 men, 8 women) had bursitis, while 143 (76 men, 67 women) had no bursitis. In evaluating knee bursitis, US, when compared to MRI, correctly identified 13 out of 15 cases of bursitis, showing a sensitivity of 86.67 %, specificity 100 %, and K index of 0.92. Particularly in the suprapatellar bursa, ultrasound showed bursitis in 5 cases versus 7 by MRI (sensitivity of 71.4 %, specificity of 100 %, and K index of 0.82). CONCLUSION: Ultrasound can be used as a valuable tool for the evaluation of bursitis of the superficial bursae in patients who cannot undergo MRI. PMID- 26261476 TI - Migration of calcium deposits into subacromial-subdeltoid bursa and into humeral head as a rare complication of calcifying tendinitis: sonography and imaging. AB - Calcifying tendinitis of the shoulder is a common condition characterized by the deposition of calcium, predominantly hydroxyapatite crystals, in the rotator cuff. A rare complication of this condition is the migration of calcium deposits from tendons, usually the supraspinatus, into the subacromial-subdeltoid bursa or into the humeral greater tuberosity. These complications are responsible for intense acute shoulder pain and functional disability. Patient anamnesis and clinical symptoms must be considered to make the diagnosis, but imaging, particularly sonography, is often necessary, showing a typical presentation related to the locations of calcium deposits. We present sonographic and other imaging features of subacromial-subdeltoid bursitis and humeral osteitis related to the migration of calcium. PMID- 26261478 TI - Association between HSD17B1 rs605059 polymorphisms and the risk of uterine diseases: a systemic review and meta-analysis. AB - The aim of this study was to evaluate the HSD17B1 gene polymorphisms in the risks of endometrial cancer, endometriosis and uterine leiomyoma by meta-analysis. A comprehensive electronic search was conducted in PubMed, Medline (Ovid), Embase, Weipu, Wanfang and CNKI. The pooled ORs were performed using the Revman 5.2 softerware. 8 case-control studies were included: 3 were about endometrial cancer, 4 were about endometriosis and 1 was about uterine leiomyoma. The result showed no significant association between HSD17B1 rs605059 gene polymorphisms and risks of endometrial cancer (AA vs. AG+GG: OR = 1.11, 95% CI = 0.94-1.32; AA+AG vs. GG: OR = 1.79, 95% CI = 0.42-7.52; AG vs. AA+ GG: OR = 0.87, 95% CI = 0.76 1.00; AA vs. GG: OR = 1.43, 95% CI = 0.62-3.30; A vs. G: OR = 1.00, 95% CI = 0.91 1.11) or endometriosis (AA vs. AG+GG: OR = 0.99, 95% CI = 0.75-1.32; AA+AG vs. GG: OR = 1.73, 95% CI = 0.92-3.25; AG vs. AA+ GG: OR = 1.24, 95% CI = 1.00-1.53; AA vs. GG: OR = 1.54, 95% CI = 0.79-2.97; A vs. G: OR = 1.23, 95% CI = 0.90 1.68). No association was found in a subgroup analysis based on Asian ethnicity for endometriosis. This meta-analysis suggested that HSD17B1 rs605059 polymorphisms were not associated with the risks of endometrial cancer and endometriosis. Further studies are needed to validate the conclusion and clarify the relationship between HSD17B1 rs605059 polymorphisms and the risk of uterine leiomyoma. PMID- 26261479 TI - Protective effect of curcumin against experimentally induced aflatoxicosis on the renal cortex of adult male albino rats: a histological and immunohisochemical study. AB - BACKGROUND: Aflatoxin contamination of foods is a worldwide problem. Chronic aflatoxin exposure is associated with kidney damage. Curcumin is a herbal agent, used in medicine with a wide range of beneficial therapeutic effects. OBJECTIVE: to evaluate the effect of curcumin against experimentally induced aflatoxicosis on the renal cortex of adult male albino rats. MATERIALS AND METHODS: Forty adult male rats were included and they were divided equally into 4 groups (10 rats each): Group I (control group), group II (Curcumin group): The rats received curcumin (200 mg/kg b.w.) orally by gastric tube for 5 days/week, group III (Aflatoxin B1 group): The rats received aflatoxin B1 (250 MUg/kg b.w./day) orally by gastric tube 5 days/week for 4 weeks, group IV (Aflatoxin B1 and Curcumin group): The rats received aflatoxin and curcumin orally by gastric tube 5 days/week for 4 weeks. Kidney specimens were prepared and sections were stained with hematoxylin and eosin, Masson's trichrome, Periodic acid Schiff, immunohistochemical detection of desmin and Bcl2. RESULTS: The tubules of group III showed degenerative and necrotic changes with disruption of basal lamina. There was a significant decrease Bcl2 expression in the tubules, but the glomeruli showed an enlargement with dilation of their capillaries lumina in some areas, while the other areas showed glomerular atrophy with obliteration of their capillaries lumina. There was a significant increase in desmin expression in the glomerular cells. The interstitium showed hemorrhage and cellular infiltration. Group IV showed improvement of the histological and immunohistochemical changes described before. CONCLUSION: Aflatoxin B1 has deleterious effects of on the histological structure of the rat's renal cortex and curcumin minimized these effects as it has antioxidant, anti-inflammatory and antiapoptotic activities. We advise eating nutritious diets that contain sufficient amounts of curcumin and regulation must implement to avoid the presence of aflatoxins in high concentrations in human food. PMID- 26261480 TI - Immunohistochemical phenotype and molecular pathological characteristics of metanephric adenoma. AB - To assess the clinicopathological, immunohistochemical and molecular features of metanephric adenoma (MA). Clinicopathologic data were obtained for 5 cases of MA with follow-up information. Specimens from these patients were stained by HE and immunohistochemistry for the detection of WT1, vimentin, S-100 protein, CK7, P504s, CD10 and renal cell carcinoma marker (RCC). Fluorescence in situ hybridization (FISH) was performed on 4 tumors. The patients included 1 male and 4 females, aged from 30 to 49 (mean=39) years. Tumor diameters ranged from 3 to 5.5 cm. Histologically, the tumors had tubular, papillary, or glomeruloid architectures, and were composed of cells with uniform and round nuclei, inconspicuous nucleoli, and high ratio of nucleus to cytoplasm. Nuclear polymorphism and mitotic figures were not observed. Immunohistochemically, they expressed WT1 (5/5), vimentin (5/5), S-100 (4/5), CK7 (2/5), P504s (2/5), and CD10 (1/5) and not RCC. FISH study was carried out on 4 metanephric adenoma cases, and no abnormalities were observed in chromosomes 3, 7, 17, and P16 gene of chromosomes 9. MA is an uncommon renal tumor. Its diagnosis depends on morphological, immunohistochemical and molecular features. PMID- 26261482 TI - delta-Cadinene inhibits the growth of ovarian cancer cells via caspase-dependent apoptosis and cell cycle arrest. AB - Ovarian cancer is one of the most common causes of mortality among all cancers in females and is the primary cause of mortality from gynecological malignancies. The objective of the current research work was to evaluate a naturally occurring sesquiterpene-delta-Cadinene for its antiproliferative and apoptotic effects on human ovary cancer (OVCAR-3) cells. We also demonstrated the effect of delta Cadinene on cell cycle phase distribution, intracellular damage and caspase activation. Sulforhodamine B (SRB) assay was used to evaluate the antiproliferative effect of delta-cadinene on OVCAR-3 cells. Cellular morphology after delta-cadinene treatment was demonstrated by inverted phase contrast microscopy, fluorescence microscopy and transmission electron microscopy. Flow cytometry was used to analyze the effect of delta-cadinene on cell cycle phase distribution and apoptosis using propidium iodide and Annexin V-fluorescein isothiocyanate (FITC)/PI kit. The results revealed that delta-cadinene induced dose-dependent as well as time-dependent growth inhibitory effects on OVACR-3 cell line. delta-cadinene also induced cell shrinkage, chromatin condensation and nuclear membrane rupture which are characteristic of apoptosis. Treatment with different doses of delta-cadinene also led to cell cycle arrest in sub-G1 phase which showed dose-dependence. Western blotting assay revealed that delta-cadinene led to activation of caspases in OVCAR-3 cancer cells. PARP cleavage was noticed at 50 uM dose of delta-cadinene with the advent of the cleaved 85-kDa fragment after exposure to delta-cadinene. At 100 uM, only the cleaved form of PARP was detectable. Pro-caspase-8 expression remained unaltered until 10 uM dose of delta cadinene. However, at 50 and 100 uM dose, pro-caspase-8 expression was no longer detectable. There was a significant increase in the caspase-9 expression levels after 50 and 100 uM delta-cadinene treatments. PMID- 26261481 TI - Curcumin inhibits cell proliferation and promotes apoptosis in human osteoclastoma cell through MMP-9, NF-kappaB and JNK signaling pathways. AB - Curcumin is a polyphenol compound extracted from ginger plant, turmeric, commonly used in a variety of food coloring and flavoring additives. Curcumin has many effects such as anti-inflammatory, anti-tumor, antioxidant and anti-microbial effects. However, the mechanism underlying the anti-cancer effect of curcumin on human osteoclastoma (Giant cell tumor, GCT) cells remains unclear. The objectives of this study were to determine the efficacy of curcumin on proliferation and apoptosis of GCT cells and its related mechanisms. In our study, cell viability, cellular apoptosis and caspase-3 activity of GCT cells were analyzed using 3.3 (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry (FCM) assay and commercial kits, respectively. Next, MMP-9 gene expression quantity, NF-kappaB activity and JNK protein expression of GCT cells were tested with real-time polymerase chain reaction (RT-PCR), commercial kits and western blotting assay, respectively. Firstly, MMP-9, NF-kappaB and JNK inhibitors were added into GCT cells and which was researched the mechanism of curcumin on human GCT cells. In this study, the efficacy of curcumin reduced cell viability, induced cellular apoptosis and increased caspase-3 activity of GCT cells. Furthermore, curcumin inhibited the MMP-9 gene expression quantity and NF kappaB activity, and activated JNK protein expression in GCT cells. Meanwhile, down-regulation of MMP-9 gene expression quantity and NF-kappaB activity could promote the anti-cancer effect of curcumin on cell viability of GCT cells. Interesting, down-regulation of JNK protein expression could also reversed the anti-cancer effect of curcumin on cell viability of GCT cells. Taken together, our results suggest that curcumin inhibits cell proliferation and promotes apoptosis in osteoclastoma cell through suppression of MMP-9 and NF-kappaB, and activation JNK signaling pathways. PMID- 26261483 TI - Effect of antisense microRNA targeting survivin on rectal cancer HRC-9698 cells and its mechanism. AB - BACKGROUND: Rectal cancer seriously threats to human health. Traditional chemotherapy drugs might kill rectal cancer cells while easy cause side effects and clinical complications. Therefore, it is necessary to explore possible new methods for rectal cancer treatment. Survivin is an important tumor-specific protein. Previous researches showed it may be closely related to nasopharyngeal carcinoma. Its role in rectal cancer remains unclear. METHODS: Cultivate human rectal cancer HRC-9698 cells. Antisense microRNA targeting survivin and control miRNA were constructed and transfected to HRC-9698 cells. MTT assay was applied to detect cell growth. Flow cytometry was used to test cell apoptosis. Western blot was performed to detect Osteopontin expression level. Colony formation and transwell assay were used to test cell clone formation and invasion abilities. RESULTS: Antisense microRNA targeting survivin can inhibit HRC-9698 cell proliferation and induce its apoptosis. Antisense microRNA targeting survivin decreased osteopontin expression level. Overexpressed osteopontin inhibited antisense microRNA targeting survivin induced cell apoptosis. Antisense microRNA targeting survivin suppressed HRC-9698 cells' colony formation and invasion abilities. CONCLUSION: Antisense microRNA targeting survivin induced osteopontin participated HRC-9698 cell apoptosis. Antisense microRNA targeting survivin inhibited HRC-9698 cell colony formation and invasive abilities, indicating that survivin may play its anti-tumor effect through inducing cell apoptosis and inhibiting cell metastasis and invasion. PMID- 26261484 TI - Upregulated expression of CD30 protein in sclerosing angiomatoid nodular transformation (SANT): studies of additional 4 cases and analyses of 6 cases previously published cases. AB - Sclerosing angiomatoid nodular transformation (SANT) of spleen is a benign lesion with a distinct morphological and immunohisochemical characteristics. Only Weinred I et al (Virchow Arch 451: 73-9, 2007) reported 6 cases of SANT expressing CD30, of which positive for EBV by in situ hybridization (EBER). 4 cases of SANT were added to investigate the clinicopathological features and focused on the expression of CD30 and EBER combined with the previously published literature. Histologically, individual angiomatoid nodules were sharply delineated by fibrocollagenous stroma with numerous vascular lumens and surrounded by a different population of spindle and ovoid cells. Angiomatoid nodules of all of the 4 cases heterogeneously expressed CD34, CD8, CD68 and diffusely demonstrated CD31 and CD30, but none were positive for EBER. We added these cases with reviewed literature to emphasize and verify the fact that upregulated expression of CD30 in SANT is quite common, which should be taken into consideration when making differential diagnosis. PMID- 26261485 TI - Expression of DNA damage checkpoint 53BP1 is correlated with prognosis, cell proliferation and apoptosis in colorectal cancer. AB - 53BP1, an important mediator of DNA damage checkpoint, plays an essential role in maintaining the cell genome stability, and the aberrant expression of 53BP1 was found to contribute to tumor occurrence and development. In this study, we explored the clinical significance of 53BP1 expression in colorectal cancer and investigated the effects of 53BP1 expression on tumor cell proliferation and apoptosis and its possible mechanisms. Immunohistochemical analysis was performed to detect the expression of 53BP1 in 95 cases of tumor tissues. After establishment of shRNA-mediated knockdown stable HCT-116 cell lines, cell proliferation, apoptosis and cell cycle distribution were detected by MTT and flow cytometry, and expression of up-and down-steam related proteins as gamma H2AX, CHK2 and P53 were tested by Western blot. 53BP1 intensity was found to be associated with tumor location (P < 0.05), and the low expression of 53BP1 revealed decreased survival time compared with high expression in subgroups as male, tumor size > 5 cm, tumor located at right side, T stage as T3-T4, N0, clinical stage as I-II (P < 0.05). In vitro, shRNA-mediated loss of 53BP1 obviously inhibited HCT-116 tumor cell apoptosis, promoted cell proliferation and increased accumulation of cells in S phase. Meanwhile, the expression of gamma H2AX, CHK2 and P53 was significantly reduced (P < 0.05). Our findings suggest 53BP1 may serve as a candidate biomarker for predicting prognosis and disease development in colorectal cancer. PMID- 26261486 TI - Astaxanthin improves cognitive deficits from oxidative stress, nitric oxide synthase and inflammation through upregulation of PI3K/Akt in diabetes rat. AB - Diabetes-induced cognitive deficit (DICD) is a prevalent disease with substantial morbidity and mortality and as a global health problem with serious economic burdens. Astaxanthin (AST) has a good prospect in production of nutritional, medical, and particularly functional health drug. The present study was aimed to study the effect of AST on DICD in diabetes mellitus (DM) rat through suppression of oxidative stress, nitric oxide synthase (NOS) pathway, inflammatory reaction and upregulation of PI3K/Akt. In the study, Morris water maze teat was used to detect the cognitive function of DM rat. Afterwards, we measured the body weight and blood glucose levels of DM rats. Then, oxidative stress, the activities of eNOS and iNOS, and inflammatory factors were analyzed using a commercial kit in cerebral cortex and hippocampus. Finally, the caspase-3/9 and phosphoinositide 3 kinase (PI3K)/Akt expressions were also checkout with Real Time PCR and immunoblotting, respectively. In this experiment, AST could availably enhance the body weight and reduce blood glucose levels of DM rats. Moreover, AST could observably perfect cognitive function of DM rat. Next, the activities of oxidative stress, nitric oxide synthase and inflammation were distinctly diminution in DM rat, after the treatment of AST. Furthermore, our present results demonstrated that AST had the protective effect on the brain cell of DM rat, decreased the caspase-3/9 expression and promoted the expression of PI3K/Akt in cerebral cortex and hippocampus. PMID- 26261487 TI - Overexpression of DNA methyltransferase 1 (DNMT1) protein in astrocytic tumour and its correlation with O6-methylguanine-DNA methyltransferase (MGMT) expression. AB - BACKGROUND: The relationship between DNA methyltransferase (DNMT) and O6 methylguanine-DNA methyltransferase (MGMT) in mediating tumorigenesis is still poorly understood. This study was carried out to investigate a correlation between DNMT1 and MGMT immunoexpression in astrocytic tumour samples. METHODS: Formalin-fixed paraffin embedded tissues of astrocytic tumour patients was obtained from an observational study conducted in Hospital Universiti Sains Malaysia (USM), which was performed from January 1997 until May 2012. Patient's histological information was retrieved from the accessible Pathology Registry. Immunohistochemistry (IHC) staining was performed to assess DNMT1 and MGMT expressions in patients' tumours. RESULTS: Our data showed that DNMT1 was highly expressed in high grade astrocytic tumours. A multiple regression analysis demonstrated a significant association of DNMT1 overexpression with tumour grade III and IV (GIII: OR=5.802; 95% CI: 1.059, 31.785; p value=0.043; GIV: OR=40.663; 95% CI=4.069, 406.347; p value=0.002). The MGMT protein was downregulated in tumours with higher grade as evident by a reduction mean H-score for MGMT expression from GI to GIV [28.36 +/- 43.88, 28.08 +/- 33.67, 26.00 +/- 48.70 and 16.20 +/- 35.61]. However, a good negative correlation was observed between DNMT1 and MGMT in high grade tumour [Spearman correlation test: r=-0.561, p value <= 0.001 in percentage expression and r=-0.576, p value <= 0.001 in H score]. CONCLUSION: DNMT1 overexpression was seen correlated with a reduction of MGMT protein expression in high grade astrocytic tumour. Understanding the role of these markers could be important to overcome astrocytic tumour aggresiveness. PMID- 26261488 TI - Knockdown of microRNA-127 reverses adriamycin resistance via cell cycle arrest and apoptosis sensitization in adriamycin-resistant human glioma cells. AB - The aim of this study was to investigate signaling pathways for reversal of microRNA-127-mediated multi-drug resistance (MDR) in gliomas cells. Adriamycin resistant glioma cell lines U251/adr and U87-MG/adr were established and we found that anti-microRNA-127 markedly reduced microRNA-127 expression levels in a time dependent manner, leading to distinct inhibition of cell proliferation and increased apoptosis and the content of intracellular Rh123. Silencing of microRNA 127 significantly increased the sensitivity of U251/ADR and U87-MG/adr cells to adriamycin, compared to cells transfected with negative control siRNA. Silencing of microRNA-127 also significantly reduced the mRNA and protein expression levels of MDR1 and MRP1, which are major ATP-binding cassette (ABC) transporter linked to multi-drug resistance in cancer cells. And Runx2, p53, bcl-2 and survivin, which are important role in cell apoptosis, also markedly changed after microRNA 127 silencing. In addition, down-regulating microRNA-127 decreased the level of phosphorylated-Akt. Our data indicate that down-regulation of micorRNA-127 can trigger apoptosis and overcome drug resistance of gliomas cells. Therefore, this resistance of adriamycin in gliomas can be cancelled by silencing expression of microRNA-127. PMID- 26261489 TI - Canine model of crush syndrome established by a digital crush injury device platform. AB - OBJECTIVE: To establish a canine model of crush syndrome (CS). METHODS: A total of 16 healthy adult female Beagle dogs were randomly divided into the control group (n=8) and the experimental group (n=8). The crush injury was created in the left hind leg of each dog in the experimental group. RESULTS: The biochemical indexes in the experimental group changed significantly compared to the values before extrusion. And they were also significantly different from the values of the control group. The glomerular capillary dilation, renal tubular epithelial cell degeneration, and renal interstitial lymphocytic infiltration were found in the kidneys. CONCLUSION: The canine CS model established by the digital crush injury device platform was successful according with the diagnosis of CS. It is good for the investigation of the CS mechanism and treatment using this model. PMID- 26261490 TI - Effect of non-steroidal anti-inflammatory drugs on the increasing the incidence of colonic anastomosis in rats. AB - BACKGROUND: Anastomotic leakage is one of serious complications of colorectal surgery. Research is inconsistent about whether non-steroidal anti-inflammatory drugs influence the healing of colorectal anastomoses and increase the incidence of anastomotic leakage. OBJECTIVE: To study the influence of NSAIDs on the healing of rat colonic anastomoses. DESIGN: This was an animal randomized-control trial. This study was approved by the ethical committee of Yangpu Hospital, Tongji University. INTERVENTION: 90 healthy Sprague-Dawley rats were randomly divided into 6 groups of 15 rats/group. Trail was performed in C (cotrol group) with no drugs, group M with morphine for analgesia, group F with flurbiprofen axeil, group L with lornoxicam, and group P with parecoxib sodium. MAIN OUTCOME MEASURES: The main outcomes measures were serological indexes including vascular endothelial growth factor, prostaglandin E2, hydroxyproline, and C reactive protein; histological specimens from the anastomotic stoma tissue including the collagen proportion, and hydroxyproline, cycloxygenase-2, and vascular endothelial growth factor content; physical indicators, including stoma fracture pressure, fracture strength and anastomotic leakage. RESULTS: No significant difference was observed among the indices of each group (P > 0.05). A significant difference occurred after operation (P < 0.05), with the data for groups K and M being dramatically higher than those for group F. LIMITATION: The study was nonblinded. CONCLUSION: The postoperative usages of non-steroidal anti inflammatory drugs can decrease the strength of anastomotic tissue, and increase the incidence of anastomotic leakage. PMID- 26261491 TI - Identification and analysis of exosomes secreted from macrophages extracted by different methods. AB - Exosomes were small vesicles secreted by many cells, and they can play an important role in cell signal transductions. Because the diameter of exosomes is about 30-100 nm, it is so difficult to collection them. In this paper, three kinds of exosomes purifying methods (density gradient ultracentrifugation method, the ultracentrifugation and ultrafiltration method, ExoQuickTM Extraction kit method) were used to collected exosomes in culture supernatants of macrophages. The morphologies of three kinds of exosomes were analyzed by transmission electron microscopy (TEM), and the characteristic molecules such as CD86, LAMP-1, HSP-70 on exosomes were analyzed with Western blot. In addition, the biological activities of exosomes purified by three kinds of methods in vitro were analyzed by ELISA and flow cytometry methods. All experimental results show that the purity and quality of exosomes collected by ExoQuickTM extraction kit and ultracentrifugation and ultrafiltration method were better, and they could enhance the expression of MHC-I in macrophages and promote cells to secrete more TNF-alpha to cause inflammatory response of macrophages. The analysis pointed out that the advantages and disadvantages of the three methods by biological activities or components of exosomes. Therefore, the ultracentrifugation and ultrafiltration method or the ExoQuickTM Extraction kit method were more suitable to be applied in the scientific research. PMID- 26261492 TI - Increased erbB3 promotes erbB2/neu-driven mammary tumor proliferation and co targeting of erbB2/erbB3 receptors exhibits potent inhibitory effects on breast cancer cells. AB - The kinase deficient erbB3 receptor frequently co-expresses and interacts with erbB2 in human breast cancer to activate the oncogenic signaling pathways, and thus promote breast cancer cell survival/proliferation. In the current study, we discovered that the expression of endogenous mouse erbB3 was increased in the mammary tumors-derived from wild type (wt) rat erbB2/neu-transgenic mice, and the co-expression of erbB2 and erbB3 significantly promoted mammary tumor proliferation in vivo. Co-immunoprecipitation assays detected a heterodimeric complex consisting of the transgene encoded protein rat erbB2 and the endogenous mouse erbB3 in the mammary tumors. Specific knockdown of mouse erbB3 dramatically inhibited proliferation of the mammary tumor cell lines-derived from the transgenic mice. Elevated expression of erbB3 protein, but not mRNA, was abserved in human breast cancer cells upon ectopic expression of erbB2. Additional studies revealed that overexpression of erbB2 downregulated three erbB3-targeting miRNAs, miR-125a, miR-125b, and miR-205, whereas the erbB2 kinase inhibitor (lapatinib) significantly enhanced expression of the three miRNAs in breast cancer cells, suggesting that erbB2 might regulate erbB3 expression through a miRNA-dependent mechanism. Furthermore, an anti-erbB3 monoclonal IgG1 antibody (Ab) in combination with Herceptin mainly inactivated Akt and significantly inhibited proliferation of erbB2-overexpressing breast cancer cells. Collectively, our data indicate that increased expression of erbB3 plays a pivotal role in activating downstream PI-3K/Akt pathway and promoting erbB2-driven mammary/breast tumorigenesis. Simultaneous targeting of erbB2 and erbB3 with two IgG1 Abs may be an effective strategy to treat breast cancer patients whose tumors overexpress both erbB2 and erbB3. PMID- 26261493 TI - Synergistic effects of snail and quercetin on renal cell carcinoma Caki-2 by altering AKT/mTOR/ERK1/2 signaling pathways. AB - Renal cell carcinoma has become the most common subtype of kidney cancer, and has the highest propensity to manifest as metastatic disease. Because of lack of knowledge in events that correlated with tumor cell migration and invasion, few therapeutic options are available. Therefore, in current study, we explore the anti-tumoral effect of a potential chemopreventive natural product, quercetin, combined with anti-sense oligo gene therapy (inhibiting Snail gene). We found that either one of them had the remarkable effects in suppressing cell proliferation and migration, inducing cell cycle arrest and apoptosis in a ccRCC cell line, Caki-2 cells. The combination of both means provides even strong suppressive effects toward these ccRCC cells. Our study, for the first time, provides the possibility of using a novel treatment for renal cancer, by combining natural product and gene therapy. PMID- 26261494 TI - Effects of Polygonatum sibiricum polysaccharide on the osteogenic differentiation of bone mesenchymal stem cells in mice. AB - Polygonatum sibiricum polysaccharide (PSP) is a traditional Chinese medicine and is widely used to treat many diseases for hundreds of years conventionally. This study was to access the effects of PSP on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in the mice. Cells collected from BALB/C mice in the bone marrow were isolated and cultured with osteogenic medium (OM) with different concentrations of PSP. The proliferation and morphological changes of BMSCs were observed using an inverted microscope. Flow cytometric analysis was used to identify the BMSCs. MTT test was performed to analyze the proliferation and viability of the cells. ELISA was used to determine the expression levels of alkaline phosphatase (ALP), osteocalcin (OC), N-terminal propeptide of type I procollagen (PINP) and bone morphogenetic protein-2 (BMP-2). Immunocytochemistry and western blot were respectively used to determine the expressions of bone sialoprotein (BSP) and SPARC/osteonectin (OSN). The growth curves of the proliferation and differentiation of the Control, OM, 17beta-E2 and PSP groups were increased. Compared to the Control and OM groups, the expression levels of ALP, OC, PINP and BMP-2 were significantly increased in the PSP induced group (P<0.05). Immunocytochemistry and western blot showed that BSP and SPARC were increased after induction of PSP compared to the OM group (P<0.05). The study demonstrates that PSP promotes the proliferation and enhances the viability of BMSCs during osteogenic differentiation. Therefore, PSP may be a potential treatment of osteoporosis in the clinic. PMID- 26261495 TI - Alternative splicing of NUMB, APP and VEGFA as the features of pancreatic ductal carcinoma. AB - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the most common form of malignancy in pancreatic carcinoma. Here we report our discovery on the correlations between transcriptional alternative splicing (AS) of NUMB, APP, VEGFA and PDAC in patients. METHODS: The expression of NUMB, APP, VEGFA from patient samples was determined by qRT-PCR. AS of these genes was examined through laser induced fluorescence capillary electrophoresis. Correlation between the AS of the genes and results from clinical laboratory examinations were analyzed. Expression of NOTHC1 and NOTCH4 as downstream target genes was examined by qRT PCR and Western blot. RESULTS: Quantitative results indicated that expression of NUMB was significantly lower in tumor tissues (TT) than in para-tumor tissues (TP) (P<0.05), while APP (P<0.01) and VEGFA (P<0.05) were significantly higher. AS transcript percentage of NUMB PRR(S) was lower in TT than TP (P<0.05). AS transcript percentage of VEGFA (105+185) was significantly lower in TT than TP (P<0.05) compared to higher expression of VEGFA (206+338) (P<0.05). Regression analysis indicated that AS transcript of NUMB PRR(L) correlated with tumor size (P<0.01), while AS transcripts of APP and VEGFA correlated with results of laboratory examinations. To reveal the correlation between AS and its downstream targets, NOTCH1 and NOTCH4 were selected as NUMB gene targets and detected to be significantly higher in TT than TP (P<0.05). CONCLUSION: Alternative splicing of APP, VEGFA and NUMB may play an important role in pathogenesis of pancreatic ductal adenocarcinoma. Among the 3 genes, PRR(L) form of NUMB gene is highly expressed in TT and positively correlated with tumor size, while PRR(S) is lacking in TT and negatively correlated with NOTCH expression suggesting that PRR(S) might be protective in tumorogenesis and shows NOTCH pathway down regulation ability. PMID- 26261496 TI - Characterization of the B cell response to Leishmania infection after anti-CD20 B cell depletion. AB - Anti-CD20 depletion therapies targeting B cells are commonly used in malignant B cell disease and autoimmune diseases. There are concerns about the ability of B cells to respond to infectious diseases acquired either before or after B cell depletion. There is evidence that the B cell response to existing or acquired viral infections is compromised during treatment, as well as the antibody response to vaccination. Our laboratory has an experimental system using co infection of C3H mice with both Leishmania major and Leishmania amazonensis that suggests that the B cell response is important to healing infected mice. We tested if anti-CD20 treatment would completely restrict the B cell response to these intracellular pathogens. Infected mice that received anti-CD20 B cell depletion therapy had a significant decrease in CD19(+) cells within their lymph nodes and spleens. However, splenic B cells were detected in depleted mice and an antigen-specific antibody response was produced. These results indicate that an antigen-specific B cell response towards intracellular pathogens can be generated during anti-CD20 depletion therapy. PMID- 26261497 TI - Piperine mediates LPS induced inflammatory and catabolic effects in rat intervertebral disc. AB - Piperine is an exact of the active phenolic component from Black pepper. It has been reported to have many biological activities including anti-oxidant, anti inflammatory and anti-tumor effects. Intervertebral disc degeneration (IDD) is a degenerative disease closely relate to inflammation of nucleus pulposus (NP) cells. This study aimed to assess the anti-inflammatory and anti-catabolic effects of piperine in rat intervertebral disc using in vitro and ex vivo analyzes. We demonstrated that piperine could inhibit LPS induced expression and production of inflammatory factors and catabolic proteases in NP cells culture model. It significantly inhibited multiple inflammatory factors and oxidative stress-associated genes (IL-1beta, TNF-alpha, IL-6, iNOS), MMPs (MMP-3, MMP-13), ADAMTS (ADAMTS-4, ADAMTS-5) mRNA expression and NO production in a concentration dependent manner. Moreover, piperine could reverse the LPS-induced inhibition of gene expression of aggrecan and collagen-II. Histologic and dimethylmethylene blue analysis indicated piperine could also against LPS induced proteoglycan (PG) depletion in a rat intervertebral disc culture model. Western blot results showed that piperine inhibited the LPS-mediated phosphorylation of JNK and activation of NF-kappaB. Finally, our results demonstrated the ability of piperine to antagonize LPS-mediated inflammation of NP cells and suppression of PG in rat intervertebral disc, suggesting a potential agent for treatment of IDD in future. PMID- 26261498 TI - Mannose prevents acute lung injury through mannose receptor pathway and contributes to regulate PPARgamma and TGF-beta1 level. AB - Mannose has been reported to prevent acute lung injury (ALI), and mannose receptor (MR) has been demonstrated to have a role. The rationale for this study is to characterize the mechanism by which mannose and MR prevent lipopolysaccharide (LPS)-induced ALI. Male ICR mice were pretreated mannose by intravenous injection 5 min before and 3 h after intratracheal instillation of LPS. Pathological changes, proinflammatory mediator, peroxisome proliferator activated receptor gamma (PPARgamma), MR, and transforming growth factor beta1 (TGF-beta1) levels were determined. The RAW264.7 cells were pretreated with mannose and stimulated with LPS for 3 h. Proinflammatory mediator and TGF-beta1 in the culture media, PPARgamma, MR, and TGF-beta1 expression in RAW 264.7 cells were measured. Mannose markedly attenuated the LPS-induced histological alterations and inhibited the production of proinflammatory mediator in mice and in RAW 264.7 cells. Mannose increased PPARgamma and MR expression, and inhibited TGF-beta1 stimulated by LPS. Interestingly, competitive inhibition of MR with mannan was associated with elimination of the anti-inflammatory effects of mannose, and reversed effects of mannose of regulation to PPARgamma and TGF beta1. MR is important in increasing PPARgamma and decreasing TGF-beta1 expression and plays a critical role in mannose's protection against ALI. PMID- 26261499 TI - Histological characteristics following a long-term nitrate-rich diet in miniature pigs with parotid atrophy. AB - The aim of this study was to investigate the histological characteristics following a 2-year nitrate-rich diet in miniature pigs with parotid atrophy. Using averages collected data from three time points at 6, 12, and 24 months following the induction of parotid gland atrophy, salivary nitrate levels of the nitrate-diet parotid-atrophied group (17.3 +/- 3.9 ng/ul) were close to those of the control group (19.6 +/- 5.1 ng/ul). Compared to the control group, the nitrate-diet group had significantly higher nitrate levels in blood (P < 0.05) and urine (P < 0.001). Histological and electron microscopy analyses showed no abnormalities in the organs of experimental or control animals. No significant differences on apoptosis rate were found in liver and kidney tissues between the standard- and nitrate-diet groups. Therefore, dietary nitrate supplementation could restore salivary nitrate levels. High-dose nitrate loading for 2 years had no observed systemic toxicity in miniature pigs with parotid atrophy. PMID- 26261500 TI - LncRNA-AP001631.9 promotes cell migration in gastric cancer. AB - Recently, an increasing number of reports have revealed that long non-coding RNAs (LncRNAs) play important roles in a variety of aspects of cell activity, and their aberrant expression is closely associated with multigenetic diseases, including carcinoma. In the present study, through microarray analysis, we screened out a new LncRNA (LncRNA-AP001631.9), which was regulated by FOXM1, a well-known carcinogenetic factor and aimed to reveal the functional roles of this novel LncRNA in gastric cancer development. The data from qRT-PCR confirmed that the expression level of LncRNA-AP001631.9 was positively correlated with that of FOXM1. The transwell and wound healing assays indicated that LncRNA-AP001631.9 was required for the migration of gastric cancer cells. The downregulation of LncRNA-AP001631.9 by small interference RNA suppressed the migratory ability of MGC803 and AGS cells, while the overexpression of LncRNA-AP001631.9 promoted the movement of BGC823 and SGC7901 cells. Furthermore, a tail vein injection was administered, and the obtained results suggested that LncRNA-AP001631.9 contributed to the distant metastasis of SGC7901 cells. Moreover, we also collected 36 paired samples of gastric cancer tissues to explore the expression levels of LncRNA-AP001631.9. The qRT-PCR data indicated that the LncRNA AP001631.9 expression was frequently increased in gastric cancer tissues. Taken together, our findings established that LncRNA-AP001631.9 plays critical roles in gastric cancer progression and can serve as a potential new target for the treatment of gastric cancer. PMID- 26261501 TI - An exogenous hydrogen sulphide donor, NaHS, inhibits the apoptosis signaling pathway to exert cardio-protective effects in a rat hemorrhagic shock model. AB - Hydrogen sulfide (H2S) has been reported to be interwined in multiple systems, specifically in the cardiovascular system. However, the mechanisms underlying remain controversial. In the present study, we assessed the cardio-protective effects of H2S in the rat hemorrhagic shock model. Hemorrhagic shock was induced in adult male Sprague-Dawley rats by drawing blood from the femoral artery to maintain the mean arterial pressure at 35-40 mmHg for 1.5 h. The rats were assigned to four groups and the H2S donor, NaHS (28 MUmol/kg, i.p.), was injected before the resuscitation in certain groups. After resuscitation the animals were observed and then killed to harvest the hearts. The morphological investigation and ultrastructural analyses were done and apoptotic cells were detected. The levels of relevant proteins were examined using Western blotting and immunohistochemical analyses. Resuscitated hemorrhagic shock induced heart injury and significantly increased the levels of serum myocardial enzymes, creatine kinase (CK) and lactate dehydrogenase (LDH) levels. Furthermore, it caused marked increase of apoptotic cells in heart tissue. Moreover, the expression of death receptor Fas and Fas-ligand, as well as the expression of apoptosis-relevant proteins active-caspase 3 and active-caspase 8 were markedly increased. Administration of NaHS significantly ameliorated hemorrhagic shock caused hemodynamic deterioration, decreased myocardial enzymes elevation, protected myocardial ultrastructure, and inhibited the expression of apoptosis-relevant proteins. It suggested that H2S might exert its cardio-protective roles via both the extrinsic Fas/FasL/caspase-8/caspase-3 pathway and the intrinsic mitochondria involved pathways. PMID- 26261502 TI - CXCR4 silencing inhibits invasion and migration of human laryngeal cancer Hep-2 cells. AB - CXCR4 has been reported in various types of human cancer, which is associated with cancer progression and metastasis. However, the investigation of CXCR4 in laryngeal cancer is extremely rare. In the present study, we used lentivirus mediated shRNA targeting CXCR4 to silenced CXCR4 expression in Hep-2 cells and evaluated the effect of long-term suppression of CXCR4 on Hep-2 growth and metastasis. The Cell proliferation was analyzed by MTS assay, and the invasion and metastasis potentials were analyzed using wound healing and transwell assays, respectively. Our results showed that lentivirus-mediated shRNA effectively infected Hep-2 cells and suppressed CXCR4 expression, and inhibited cell growth of Hep-2 cells. Cell invasion and apoptosis were decreased concomitantly with the reduction in CXCR4 protein expression. Further analysis revealed that CXCR4 silencing caused the reducion of CXCR4, CXCL12, TIMP2, VEGF and MMP9, and the phosphorylation levels of IkappaB, AKT and MAPK, and also decreased the activity of NF-kappaB. These results suggested that knockdown of CXCR4 inhibits the invasion and metastasis of Hep-2 through PI3K/AKT and MAPK signaling pathways, by decreasing NF-kappaB activities to down-regulate VEGF, TIMP-2 and MMP-9 expression. These data demonstrate that the inhibition of CXCR4 may be an effective interventional therapeutic strategy in laryngeal cancer. PMID- 26261503 TI - Expression of HMGB1/RAGE protein in renal carcinoma and its clinical significance. AB - OBJECTIVE: To investigate the expression of high mobility group protein B1 (HMGB1) and its receptor, receptor for advanced glycation end-product (RAGE), in renal cancer tissue and surrounding normal tissue and to analyze the relationship between the expression level of the protein and receptor as well as the clinical pathological characteristics and prognosis in renal cancer patients. METHODS: A total of 80 renal carcinoma patients who were surgically treated in our hospital from February 2004 to December 2012 were included in this study. Normal paratumoral tissues were collected as a control. All diagnoses were confirmed with a postoperative pathological examination. All patients had complete pathological data. The expression of HMGB1/RAGE proteins in renal cancer tissue and paratumoral tissue was examined using immunohistochemical methods. RESULTS: The positive expression rate of HMGB1 was 71% in renal cancer tissue, which was significantly higher than that in the paratumoral normal tissue (25%). The positive expression rate of RAGE was 72% in renal cancer tissue, which was significantly higher than that in the paratumoral normal tissue (27%). Further analysis did not indicate a correlation between the positive expression of HMGB1 and RAGE proteins and gender, age and tumor size (P > 0.05), whereas the expression patterns were shown to correlate with tumor differentiation, clinical stage and lymph node metastasis (P < 0.05). The expression of HMGB1 exhibited a significant positive correlation with RAGE level (P < 0.05), the expression of HMGB1/RAGE proteins exhibited a negative correlation with the prognosis of patients, and the five-year survival rate of patients with positive expression was significantly lower than that of patients with negative expression (P < 0.05). CONCLUSION: HMGB1/RAGE exhibited significantly elevated expression in renal cancer tissues that was closely related to the clinical prognosis of patients; thus, the expression levels may become a new target in the treatment of renal carcinoma. PMID- 26261504 TI - Nigella sativa amliorates inflammation and demyelination in the experimental autoimmune encephalomyelitis-induced Wistar rats. AB - Multiple sclerosis (MS) is the major, immune-mediated, demyelinating neurodegenerative disease of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model of MS. The aim of the present study was to investigate the protective and ameliorative effects of N. sativa seeds (2.8 g/kg body weight) in EAE-induced Wistar rats. EAE induced rats were divided into: 1- EAE-induced rats ("EAE" group). 2- "N. sativa + EAE" group received daily oral administration of N. sativa 2 weeks prior EAE induction until the end of the experiment. 3- "EAE + N. sativa" group received daily oral administration of N. sativa after the appearance of first clinical signs until the end of the experiment. All animals were decapitated at the 28th day post EAE-induction. EAE was investigated using histopathological, immunohistochemical and ultrastructural examinations in addition to determination of some oxidative stress parameters in the cerebellum and medulla. N. sativa suppressed inflammation observed in EAE-induced rats. In addition, N. sativa enhanced remyelination in the cerebellum. Moreover, N. sativa reduced the expression of transforming growth factor beta 1 (TGF beta1). N. sativa seeds could provide a promising agent effective in both the protection and treatment of EAE. PMID- 26261505 TI - Enhanced expression of stem cell markers and drug resistance in sphere-forming non-small cell lung cancer cells. AB - There is growing evidence suggesting that cancer stem cells (CSCs) are playing critical roles in tumor progression, metastasis and drug resistance. However, the role of CSCs in non-small cell lung cancer (NSCLC) remains elusive. In this study, we enriched for stem-like cells from tumor spheres derived from NSCLC cell line A549 cultured in serum-free medium. Our results showed that sphere-derived cells expressed various stem cell markers such as CD44, CD133, Sox2 and Oct4. Compared with the corresponding cells in monolayer cultures, sphere-derived cells showed marked morphologic changes and increased expression of the stem cell markers CD133. Furthermore, we found that sphere-derived cells exhibited increased proliferation, cell-cycle progression as well as drug-resistant properties as compared to A549 adherent cells. Consistently, expression of several drug resistance proteins, including lung resistance-related protein (LRP), glutathion-S-transferase-pi (GST-pi) and multidrug resistance proteins-1 (MRP1) were all significantly enhanced in sphere-derived cells. These results indicate the enrichment of CSCs in sphere cultures and support their role in regulating drug resistance in NSCLC. PMID- 26261506 TI - Inhibitory effects of oleoylethanolamide (OEA) on H2O2-induced human umbilical vein endothelial cell (HUVEC) injury and apolipoprotein E knockout (ApoE-/-) atherosclerotic mice. AB - Atherosclerosis (AS) is initiated by vascular endothelial cell injury, which is induced by lipid and protein oxidation. Oleoylethanolamide (OEA), a dietary fat derived lipid, has shown atheroprotective effect. In vitro studies demonstrated that OEA showed cytoprotective effects on H2O2-induced primary cultured human umbilical vein endothelial cell (HUVEC) injury model. Further investigation of the cytoprotective effects of OEA demonstrated that OEA exerted its function by scavenging for reactive oxygen species, as well as increasing anti-oxidative enzymes, reducing lipid peroxidation, terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling (TUNEL)-positive cells and apoptosis-related proteins expression. The in vivo study using an ApoE-/- mouse model fed with high fat diet for 8 weeks showed that OEA (10 mg/kg/day, i.g.) administration reduced blood lipid levels, prevented endothelial cell damage and inhibited early AS plaque formation. In conclusion, our results suggested that OEA exerted a pharmacological effect on ameliorating atherosclerotic plaque formation through the inhibition of oxidative stress-induced endothelial cell injury and therefore OEA can be a potential candidate drug for anti-atherosclerosis. PMID- 26261507 TI - MiR-34c-3p suppresses the proliferation and invasion of non-small cell lung cancer (NSCLC) by inhibiting PAC1/MAPK pathway. AB - MicroRNAs have become recognized as key players in the development of malignancy. They are a family of small non-coding RNAs (22 nt~30 nt) that can negatively regulate the expression of cancer-related genes by sequence selective targeting of mRNAs, leading to either mRNA translational repression or degradation. Lung cancer is the leading cause of cancer-related death worldwide with a substantially low survival rate. In this study, we analyzed the expression profile of miR-34c-3p in non-small cell lung cancer (NSCLC) tissues and cell lines, as its participation in some other types of cancer has been shown by previous reports. We found that miR-34c-3p was downregulated both in NSCLC tissues and cell lines. Overexpression of miR-34c-3p suppressed cell proliferation and colony formation and also limited migration and invasion in A549 cells. Furthermore, our results also shown miR-34c-3p reduction was associated with increased PAC1 expression levels in which miR-34c-3p downregulated PAC1 expression by recognizing and binding to specific binding sites in PAC1 3'-UTR. Taken together, our study implicates important roles of miR 34c-3p in NSCLC pathogenesis and implicates its potential application in cancer therapy. PMID- 26261508 TI - Chinese medicine Tongxinluo reduces atherosclerotic lesion by attenuating oxidative stress and inflammation in microvascular endothelial cells. AB - Oxidative stress and inflammation are the important pathological basis of atherogenesis. So, attenuating oxidative stress and inflammation has a very important significance in the prevention and treatment of atherosclerosis. The aim of present study was to investigate whether anti-atherosclerotic effect of Tongxinluo (TXL), a compound traditional Chinese medicine, is related to its anti oxidation and anti-inflammation in human cardiac microvascular endothelial cells (HCMEC). We found that TXL treatment significantly reduced serum lipid levels and atherosclerotic plaque formation of apoE-deficient mice, and improved endothelial cell function as evidenced by increased expression of CD31 and eNOS. TXL pretreatment could abrogate the up-regulation of ROS and MDA induced by C16. Further experiments showed that the anti-oxidative effect of TXL may be related to inhibiting the expression of p22(phox), p47(phox) and HO-1 in HCMECs. We also found that TXL could inhibit the release of IL-1beta and TNFalpha induced by C16, which is mediated by inhibiting the expression and activation of NF-kappaB. In conclusion, TXL decreases atherosclerotic plaque formation and improves endothelial cell function by inhibiting oxidative stress and inflammation in HCMECs. This finding provides a new molecular mechanism for the anti atherosclerotic effect of TXL. PMID- 26261509 TI - KDM6B induces epithelial-mesenchymal transition and enhances clear cell renal cell carcinoma metastasis through the activation of SLUG. AB - Clear cell renal cell carcinoma (ccRCC) is one of the most common kidney cancers; epithelial-mesenchymal transition (EMT) is associated with carcinoma invasion and metastasis. There have been several studies about the molecular regulation of EMT, but the relationship between histone demethylase and EMT is little known. Here, we reported KDM6B has high expression level in ccRCC and is positively correlated with poor ccRCC prognosis. KDM6B, also known as JMJD3, is a histone demethylase, can remove repressive histone H3K27me3 marks from chromatin, thereby activating gene expression. We found that the knockdown of KDM6B could inhibit ccRCC tumorigenesis in vitro; furthermore, KDM6B could induce EMT in ccRCC cells by activating the expression of master transcription factor SLUG. ChIP assays revealed that KDM6B stimulated SLUG expression by demethylate histone H3K27me3. The knockdown of KDM6B strongly inhibited ccRCC cell invasion in vitro, while the overexpression of KDM6B shown the opposite trend. Meanwhile, our analysis of the ccRCC tissue found that KDM6B expression was significantly corresponded with lymph node metastasis. Together, our data provide a novel epigenetic mechanism regulating tumor cell invasion and EMT, and provide a biomolecule for ccRCC diagnosis and prognosis. PMID- 26261510 TI - Clinicopathological characteristics and prognosis of alpha-fetoprotein positive gastric cancer in Chinese patients. AB - PURPOSE: This study aimed to review the clinicopathological, histochemical, and prognostic features of Alpha-Fetoprotein (AFP) positive gastric cancer. PATIENTS AND METHODS: Six hundred and fifty one patients with gastric cancer who underwent gastrectomy between January 2009 and December 2012 at The First Hospital of Jilin University were enrolled in the study. Among them, 45 patients were identified as AFP positive gastric cancer. The clinicopathologic characteristics and prognosis of the AFP positive gastric cancer patients were analyzed. RESULTS: Among the 45 AFP positive patients, serum levels of AFP were < 100 ug/L in nine patients. The histological classification of 45 patients was as follows: hepatoid type, 25 (55.6%) cases; fetal gastrointestinal type, 12 (26.7%) cases; yolk sac tumor type, 2 (4.4%) cases; and mixed type, 6 (13.3%) cases. Twenty nine (64.4%) cases were AFP positive by immunohistochemical analysis; we found no significant difference in AFP positivity and histologic type. However, the differences in the number of metastasis lymph nodes, the maximum tumor diameter, pathological stage, vascular invasion and liver metastasis between the AFP positive group and the negative group were significant. At the same T stage, the liver metastasis status of the AFP positive group was higher than that of the negative group. The AFP positive group had a much poorer prognosis than the negative group. CONCLUSION: AFP positive gastric cancer is associated with aggressive behavior and poorer prognosis compared to that of AFP negative gastric cancer. PMID- 26261511 TI - MiR-135 post-transcriptionally regulates FOXO1 expression and promotes cell proliferation in human malignant melanoma cells. AB - Malignant melanoma is the deadliest form of all skin cancers. Recently, microRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression by targeted repression of transcription and translation and play essential roles during cancer development. Our study showed that miR-135a is upregulated in malignant melanoma tissues and cell lines by using Real-time PCR assay. Enforced expression of miR-135a in malignant melanoma cells promotes cell proliferation, tumorigenicity, and cell cycle progression, whereas inhibition of miR-135a reverses the function. Additionally, we demonstrated FOXO1 is a direct target of miR-135a and transcriptionally down-regulated by miR-135a. Ectopic expression of miR-135a led to downregulation of the FOXO1 protein, resulting in upregulation of Cyclin D1, and downregulation of P21(Cip1) and P27(Kip1) through AKT pathway. Our findings suggested that miR-135a represents a potential onco-miRNA and plays an important role in malignant melanoma progression by suppressing FOXO1 expression. PMID- 26261512 TI - Comparison of systemic inflammation response and vital organ damage induced by severe burns in different area. AB - BACKGROUND: In this study, we will establish a stable and optimized rat model that can meet strictly diagnosed criteria and serve as a tool to investigate the potential of novel therapeutics in this preclinical model through comparative analysis of systemic alterations, levels of pro-inflammatory cytokines in serum and infiltrated numbers of inflammatory cells in distant organ between 30% and 50% TBSA with a full-thickness burn. MATERIALS AND METHODS: The adult male Wistar rats were randomly divided into the following groups: control group, 30% TBSA with a full-thickness burn group, and 50% TBSA with a full-thickness burn group. The blood and serum samples in the 3 groups were collected and detected by blood routine examination and biochemical detection at 6 h, 12 h, 24 h and 48 h post burn. The levels of TNF-alpha, IL-1beta and IL-6 in serum were detected by ELISA. The sections of lung, renal, liver and heart were analyzed by H&E and immunohistochemical staining detection. RESULTS: Our results showed that temperature in 50% TBSA with a full-thickness burn group was always hypothermia, and lower than 36 degrees C at defined timepoints post burn, that was in 30% TBSA with a full-thickness burn group was lower than 36 degrees C only at 48 h post burn. The levels of TNF-alpha, IL-1beta and IL-6 were significantly increased in 30% and 50% groups at 6 h, 12 h, 24 h and 48 h post burn. The apoptosis in distant organs and the biochemical parameters such as ALT, AST, troponin, CK, CK MB, LDH, urea and creatinine in 30% and 50% groups were also increased at different degrees at defined timepoints after burn, but changes in 50% group were more obvious than that in 30% group. CONCLUSION: We choose 50% TBSA with a full thickness burn to establish a stable and optimized rat model that can meet strictly diagnosed criteria and serve as a tool to investigate the potential of novel therapeutics in this preclinical model. PMID- 26261513 TI - Knockdown of Nestin inhibits proliferation and migration of colorectal cancer cells. AB - Nestin, a member of type VI intermediate filament protein family, is widely expressed in mammalian nervous tissue and stem/precursor cells of non-neuronal normal tissues. Nestin has also been investigated to determine possible tumor promoting functions. However, whether Nestin is involved in colorectal cancer (CRC) cells remains unclear. In this report, Nestin expression was upregulated in stromal cells of human CRC tissues. Endogenous Nestin expression in CRC cell lines SW480 and HCT116 was knocked down by a lentivirus. MTT and colony formation assays revealed that Nestin deletion significantly inhibits the proliferation of CRC cell lines; flow cytometer analysis showed that Nestin deletion causes cell cycle arrest at S phase. Transwell chamber and wound healing scratch assays also revealed that Nestin deletion suppresses cell migration. Our findings indicated that Nestin plays an essential role in CRC progression; thus, Nestin can be applied as a therapeutic target of CRC. PMID- 26261514 TI - Syndecan-4 shedding is involved in the oxidative stress and inflammatory responses in left atrial tissue with valvular atrial fibrillation. AB - Oxidative stress and inflammation play critical roles in the development and maintenance of atrial fibrillation (AF). In addition, syndecan-4 (Synd4) shedding induced by oxidative stress or inflammation plays a role in the migration of inflammatory cells. Therefore, we hypothesized that Synd4 shedding was also involved in the inflammatory response in atrial fibrillation patients with valvular heart disease. To confirm this suppose, left atrial appendages and clinical data were obtained from 65 patients with valvular disease undergoing valve surgery. Ten left atrial appendages obtained from healthy heart donors were used as controls. Analyses including histopathology, western blotting, and enzyme kinetics were performed to assess the oxidative injury, inflammation responses, and Synd4 shedding. The results showed that the inflammatory response and oxidative injury were increased significantly, whereas as levels of the Synd4 ectodomain was decreased significantly in AF patients. Furthermore, Synd4 ectodomain levels were correlated with atrial oxidative and inflammatory markers. The results showed that Synd4 shedding is a molecular pathological alteration in the development and maintenance of inflammation-associated AF. PMID- 26261515 TI - MiR-218 inhibits multidrug resistance (MDR) of gastric cancer cells by targeting Hedgehog/smoothened. AB - Multidrug resistance (MDR) is the main obstacle to successful chemotherapy for patients with gastric cancer. The microRNA miR-218 influences various pathobiological processes in gastric cancer, and its down-regulation in this disease raises the question of whether it normally inhibits MDR. In this study we observed that two MDR gastric cancer cell lines showed lower expression of miR 218 compared with their chemosensitive parental cell line. Overexpressing miR-218 chemosensitizes gastric cancer cells, slowed efflux of adriamycin, and accelerated drug-induced apoptosis. We identified the smoothened (SMO) gene as a functional target of miR-218, and found that SMO overexpression counteracts the chemosensitizing effects of miR-218. These findings suggest that miR-218 inhibits MDR of gastric cancer cells by down-regulating SMO expression. PMID- 26261516 TI - Effects of rhBNP on myocardial fibrosis after myocardial infarction in rats. AB - PURPOSE: We aimed to observe the effects and mechanism of rhBNP treatment on myocardial fibrosis (MF) after myocardial infarction (MI). METHODS: SPF rats were separated into 3 groups: normal, MI (ligation of left coronary artery), and MI + rhBNP (recombinant human brain natriuretic peptide). Rats in MI + rhBNP group were given 30 MUg/kg for 2 days before modeling and for 4 weeks after modeling. mRNA levels and the expression levels of TGF-beta1 (transforming growth factor) and CTGF (connective tissue growth factor) in 3 groups were analyzed using the RT qPCR and western blotting analysis, respectively. Furthermore, myocardial volume fraction (CVF) was analyzed using the Sirius Red F3B (SR) while the percentage of type I and III collagen in 3 groups were analyzed using the immunohistochemical staining. RESULTS: Compared with the normal group, the levels of TGF-beta1, CTGF, CVF, type I and III collagen were higher in MI group. However, mRNA levels of TGF beta1 and CTGF were significantly decreased in MI + rhBNP compared to MI groups. Expression of TGF-beta1 was lower while that of CTGF was higher in MI + rhBNP group than that in MI group. Besides, CVF, and type I and III collagen were lower in MI + rhBNP group compared with MI group. CONCLUSION: rhBNP could significantly decrease the TGF-beta1 and CTGF levels in post-MI so as to inhibit the type I and III collagen deposition in MF of post-MI. rhBNP will be benefit for the improvement of MF. PMID- 26261517 TI - Retinoic acid aliphatic amide inhibits the AMPK-HIF-1alpha pathway in human ovarian cancer. AB - Ovarian carcinoma the commonly observed gynecological cancers has a high mortality rate. In the present study effect of retinoic acid aliphatic amide (RACA) in ovarian cancer cells was investigated using proliferation, migration and invasion assays. Western blot was used to examine the Bcl-2, cleaved caspase 3, p-ERK, MMP-2, p-FAK, P-P38, p-AMPKalpha and HIF-1alpha protein expression. CoCl2 was used to induce HIF-1alpha expression in SKOV3ip. 1 and HEY-A8 cells. The results revealed that RACA treatment prompted cell proliferation, invasion and migration but inhibited apoptosis of SKOV3ip. 1 and HEY-A8 cells. RACA treatment also induced upregulation of Bcl-2 and MMP-2, activation of p-P38, p ERK and p-FAK, inhibition of cleaved caspase 3. RACA treatment also caused upregulatation of HIF-1alpha in ovarian cells with the activation of p-AMPKalpha. Upregulation of HIF-1alpha expression in CoCl2-treated cancer cells resulted in decrease in SDHB. Thus RACA plays a key role in cell proliferation, invasion, migration and apoptosis of human ovarian carcinoma through AMPK-HIF-1alpha pathway. PMID- 26261518 TI - Huperzine A protects neural stem cells against Abeta-induced apoptosis in a neural stem cells and microglia co-culture system. AB - OBJECTIVES: This study aims to explore whether Huperzine A (HupA) could protect neural stem cells against amyloid beta-peptide Abeta induced apoptosis in a neural stem cells (NSCs) and microglia co-culture system. METHODS: Rat NSCs and microglial cells were isolated, cultured and identified with immunofluorescence Assays (IFA). Co-culture systems of NSCs and microglial cells were employed using Transwell Permeable Supports. The effects of Abeta1-42 on NSCs were studied in 4 groups using co-culture systems: NSCs, Abeta+NSCs, co-culture and Abeta+co culture groups. Bromodeoxyuridine (BrdU) incorporation and flow cytometry were utilized to assess the differences of proliferation, differentiation and apoptosis of NSCs between the groups. LQ test was performed to assess the amounts of IL-6, TNF-alpha and MIP-alpha secreted, and flow cytometry and Western blotting were used to assess apoptosis of NSCs and the expressions of Bcl-2 and Bax in each group. RESULTS: IFA results showed that isolated rat NSCs were nestin positive and microglial cells were CD11b/c-positive. Among all the groups, the Abeta+co-culture group has the lowest BrdU expression level, the lowest MAP2 positive, ChAT-positive cell counts and the highest NSC apoptosis rate. Smaller amounts of IL-6, TNF-alpha and MIP-alpha were being secreted by microglial cells in the HupA+Abeta+co-culture group compared with those in the Abeta+ co-culture group. Also the Bcl-2: Bax ratio was much higher in the HupA+Abeta+co-culture group than in the Abeta+co-culture group. CONCLUSIONS: HupA inhibits cell apoptosis through restraining microglia's inflammatory response induced by Abeta1 42. PMID- 26261519 TI - Formononetin sensitizes glioma cells to doxorubicin through preventing EMT via inhibition of histone deacetylase 5. AB - Chemoresistance is a major obstacle to successful chemotherapy for glioma. Formononetin is a novel herbal isoflavonoid isolated from Astragalus membranaceus and possesses antitumorigenic properties. In the present study, we investigated the anti-proliferative effects of formononetin on human glioma cells, and further elucidated the molecular mechanism underlying the anti-tumor property. We found that formononetin enhanced doxorubicin cytotoxicity in glioma cells. Combined treatment with formononetin reversed the doxorubicin-induced epithelial mesenchymal transition (EMT) in tumor cells. Moreover, we found that formononetin treatment significantly decreased the expression of HDAC5. Overexpression of HDAC5 diminished the suppressive effects of formononetin on glioma cell viability. Furthermore, knockdown of HDAC5 by siRNA inhibited the doxorubicin induced EMT in glioma cells. Taken together, these results demonstrated that formononetin-combined therapy may enhance the therapeutic efficacy of doxorubicin in glioma cells by preventing EMT through inhibition of HDAC5. PMID- 26261520 TI - MiRNA-15a inhibits proliferation, migration and invasion by targeting TNFAIP1 in human osteosarcoma cells. AB - Recent data strongly suggest the important role of miRNAs in various cancer related processes. Osteosarcoma is the most common type of primary malignant bone tumor and is characterized by complex genetic changes and resistance to conventional treatments. In this study, the role of miRNA-15a (miR-15a) in the progression and metastasis of osteosarcoma was investigated. The result demonstrated that the expression of miR-15a was down-regulated in osteosarcoma tissues and cell lines as compared with that in adjacent non-neoplastic bone tissues and the osteoblastic cell line. In functional assays, miR-15a inhibited cell proliferation, migration and invasion in U2OS and MG-63 cells. Meanwhile, bioinformatic analysis combined with experimental confirmation demonstrated that tumor necrosis factor; alpha-induced protein 1 (TNFAIP1) gene is a potential target of miR-15a and can be directly regulated by miR-15a. Down-regulation of TNFAIP1 induced effects on osteosarcoma cell lines similar to those induced by miR-15a. Taken together, these data suggest that miR-15a may act as a tumor suppressor, which is commonly down-regulated in both osteosarcoma tissues and cells. TNFAIP1 plays an important role in mediating miR-15a dependent biological functions in osteosarcoma. Reintroduction of miR-15a may be a novel therapeutic strategy by down-regulating TNFAIP1 expression. PMID- 26261521 TI - GPX3 promoter is methylated in chronic myeloid leukemia. AB - Hypermethylation of GPX3 (glutathione peroxidase 3) promoter has been identified in various cancers. However, the pattern of GPX3 promoter methylation in chronic myeloid leukemia (CML) remains unknown. Our study was aimed to investigate the methylation status of GPX3 promoter and its clinical relevance in CML. Real-time quantitative methylation-specific PCR and bisulfite sequencing PCR was performed to detect the level of GPX3 methylation in 80 CML patients and 44 controls. GPX3 promoter in CML patients was significantly methylated compared with controls (P = 0.007). GPX3 highly methylated patients showed significantly older age than GPX3 lowly methylated patients (P = 0.037). However, patients with GPX3 methylation had significantly lower white blood cells than those with low GPX3 methylation (P = 0.006). BCR-ABL transcript in GPX3 highly methylated patients was a little lower than that in GPX3 lowly methylated patients (P = 0.161). No significant differences were observed in the frequency of GPX3 methylation in the different stages of CML (P = 1.000). Significantly negative correlation was observed between GPX3 expression and GPX3 methylation (R = -0.442, P = 0.004). GPX3 mRNA level in K562 cell line was significantly increased after 5-aza-2'-deoxycytidine treatment, and GPX3 methylation level was decreased. GPX3 hypermethylation is frequent in CML and is negatively associated with its expression. PMID- 26261522 TI - Association of ultrasonographic features with NGX6 expression and prognosis in invasive ductal breast carcinoma. AB - INTRODUCTION: Nasopharyngeal carcinoma-associated gene 6 (NGX6) is a newly discovered tumor suppressor gene. It contains one epidermal growth factor (EGF) like domain. Many studies have shown that proteins contain (EGF)-like domain structure affect a variety of biological actions. However, little is known about the relationships between NGX6 expression and biological behaviors in invasive ductal breast carcinoma (IDBC). The study discussed the association of ultrasonographic features with NGX6 expression and prognosis in IDBC. METHODS: Ultrasonographic feature and clinical data in 122 patients with IDBC were retrospectively analyzed. NGX6 expression of IDBC was measured using immunohistochemistry methods. RESULTS: The incidence of the burr sign, lymph node metastasis and abundance blood flow in NGX6 expression negative groups were higher than those in positive groups. Kaplan-Meier analysis showed that the association between NGX6 positive expression and higher disease-free survival (DFS) or higher overall survival (OS); Lymph node metastasis is associated with lower DFS or lower OS; Lower blood flow grade is associated with higher DFS. In univariate and multivariate survival analysis, NGX6 expression, lymph node metastasis, TNM and the blood flow grade were the independent prognostic factors for DFS and OS of IDBC. CONCLUSIONS: ultrasonographic features are associated with NGX6 expression in IDBC. NGX6 is involved in the invasion and metastasis activity of IDBC. Our results suggest that NGX6 may be employed as a promising prognostic factor and useful therapeutic target for IDBC. Combination of ultrasonic findings and NGX6 detection may yield clinically useful information for IDBC prognosis. PMID- 26261523 TI - Effects of dexmedetomidine on the protection of hyperoxia-induced lung injury in newborn rats. AB - Dexmedetomidine (Dex) is a specific agonist of alpha2-adrenoceptor and was reported to have protective effect on a variety of organs, however the effect of Dex on hyperoxia-induced lung injury remains unknown. In the present study, Dex was administrated to newborn rats and its effect against hyperoxia-induced lung injury was examined. The results showed that, Dex significantly attenuated the aberration, macrophage infiltration, inflammatory responses and pulmonary edema induced by hyperoxia. In addition, the down-regulation of AQP1 was also reversed by Dex. These data indicate that Dex may be a potential therapy in the prevention of hyperoxia-induced lung injury in infants. PMID- 26261524 TI - Ischemic postconditioning provides protection against ischemia-reperfusion injury in intestines of rats. AB - In the present study, we investigated the protective role of ischemic postconditioning (IPOST) against intestine ischemia-reperfusion (I/R) injury in rats. Male Sprague-Dawley rats were divided into sham-operation group (S), I/R group (I/R), ischemic preconditioning group (IPC), ischemic postconditioning group (IPOST). After reperfusion, small intestines were resected for histopathologic evaluations. To evaluate DNA fragmentation, resolving agarose gel electrophoresis was performed. To measure cellular apoptotic rates in intestine tissues, we performed TUNEL staining. To examine lipid peroxidation, production of superoxide radicals and tissue neutrophil infiltration, we tested the content of malondialdehyde and activities of superoxidase dismutase and myeloperoxidase in intestine tissues, respectively. Under light microscope, intestinal mucosal impairment in IPOST and IPC groups was found milder than that in I/R group (P < 0.05). The number of apoptosis cells in I/R group was significantly higher than that in IPOST and IPC groups (P < 0.05). The content of malondialdehyde and activity of myeloperoxidase were significantly reduced in IPOST group and IPC group compared with I/R group, but the activity of superoxidase dismutase in IPOST group and IPC group was enhanced compared with I/R group (P < 0.05). These results suggest that IPOST results in protection against intestine I/R injury, which may be related to reduced production of reactive oxygen species, enhanced activities of antioxidant systems and inhibited apoptosis of intestinal mucosal cells. PMID- 26261525 TI - JMJD5 is a potential oncogene for colon carcinogenesis. AB - OBJECTIVE: To observe the effects of Jumonji C domain-containing (JMJD) 5 depletion on colon cancer (CC). METHODS: A short-hairpin RNA targeting JMJD5 was transfected into a lentivirus to make Lv-shJMJD5 for infection into the Caco-2 human cell. Besides, a negative control shRNA was constructed. The mRNA and protein levels of JMJD5 were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. Cell proliferation, migration, and invasion were assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide (MTT), soft agar colony assay and transwell assay, respectively. In addition, immunohistochemical (IHC) staining was performed to investigate the expression of JMJD5 in adjacent normal tissues and tumor tissues from patients with CC. RESULTS: Compared with control group, mRNA and protein levels of JMJD5 was significantly reduced after infection with Lv-shJMJD5 (P<0.05), and Caco-2 cell proliferation, migration, and invasion were all obviously inhibited (P<0.05). The results of IHC showed that JMJD5 was significantly up-regulated compared with normal tissues (P<0.01). Additionally, follow-up data demonstrated that the survival rate of patients with high expression of JMJD5 was obviously lower than that with low expression (P<0.01). CONCLUSIONS: JMJD5 depletion could significantly inhibit human CC cell proliferation, migration, and invasion, implying that JMJD5 might be a potential oncogene. PMID- 26261526 TI - Decreased irisin secretion contributes to muscle insulin resistance in high-fat diet mice. AB - AIMS: Recent studies have revealed the relationship between irisin and insulin signaling, while positive associations of muscle FNDC5 with insulin resistance is observed. However, the functional mechanism of irisin on muscle insulin resistance is still obscure. This study aims to investigate the effect of irisin on muscle insulin action. METHODS: Diabetic mouse model was established by high fat diet (HFD) induced obesity in C57BL/6 mice. Body indexes and serum levels of triglyceride (TG), blood glucose and insulin were record. Oral glucose tolerance test (OGTT) was performed before being killed. Circulating irisin level was also detected, while FNDC5/irisin expression was determined by RT-PCR and western blot analysis in both muscle and adipose tissues. Insulin action was further evaluated by the phosphorylation of AKT and Erk, and palmitic acid treated muscle cells were introduced for mimicking diabetic status in vitro. RESULTS: Obvious obese feathers associated with type 2 diabetes were observed in HFD feeding mice, with decreased circulating irisin level and FNDC5/irisin secretion in adipose tissues. Although FNDC5/irisin expression showed little change in skeletal muscle, the insulin action was inhibited significantly. Moreover, palmitic acid treated muscle cells showed similar inhibition of insulin action, and FNDC5/irisin expression change. Besides, insulin action could be reversed by irisin addition in muscle cells. CONCLUSION: HFD induced obese mice showed decreased irisin secretion from adipose tissues, which might contribute to muscle insulin resistance. Furthermore, irisin addition could recover insulin action in palmitic acid treated muscle cells, indicating the importance of irisin for preserving insulin signaling. PMID- 26261527 TI - Effects of GPNMB on proliferation and odontoblastic differentiation of human dental pulp cells. AB - Glycoprotein (transmembrane) nonmetastatic melanoma protein b (GPNMB) plays crucial roles in odontogenesis. However, the role of GPNMB in human dental pulp cells (hDPCs) is still unclear. Therefore, in this study, we investigated the expression and function of the GPNMB in odontoblastic differentiation of hDPCs. Cells were cultured in odontoblast differentiation-inducing medium; the expression of the GPNMB was assessed by reverse transcriptase polymerase chain reaction and Western blot analysis. We performed gene knockdown of GPNMB in hDPCs using lentivirus-mediated small interfering RNA (siRNA)-GPNMB. The proliferation of cells was measured by the MTT assay, and the differentiation of cells was detected with alkaline phosphatase (ALP) activity assay, qRT-PCR and Western blot were used to determine the expression levels of dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1). The expression level of GPNMB was significantly increased during odontoblastic differentiation of hDPCs. Suppression of GPNMB expression by siRNA-GPNMB obviously promoted the proliferation of hDPCs. Furthermore, siRNA-GPNMB significantly inhibited the activity of ALP and expression levels of DSPP and DMP-1 during odontoblastic differentiation of hDPCs. Our results show that GPNMB plays an important role in regulating the expression of key pluripotency genes in hDPCs and modifying odontogenic differentiation. PMID- 26261528 TI - Unfolded protein response mediated JNK/AP-1 signal transduction, a target for ovarian cancer treatment. AB - Researches have revealed several stressors, which could activate unfolded protein response (UPR) in cells. However, the survival or death pathway was determined by the duration of UPR exposure. Based on the UPR mediated death pathway, our study was aimed to investigate role of UPR on c-Jun N-terminal kinase (JNK)/activator protein-1 (Ap-1) signal transduction in diindolylmethane (DIM) treated ovarian cancer cell lines. Activation of UPR proteins, UPR mediated apoptotic signaling proteins and expression level of EpCAM, JNK, Ap-1, Caspase-3 and Bcl-2 were measured. Protein and gene expression, transcription factor activity, and protein phosphorylation were measured using standard molecular biology techniques. Our results demonstrated DIM treatment had significantly increased the expression of Endoplasmic reticulum (ER) stress regulators such as Bip, IRE1, CHOP and activation of UPR related apoptotic proteins in ovarian cancer cells. Decreased expression of EpCAM and activity of AP-1 transcription factor were observed in DIM treated cells. The pharmacologic inhibitors of the JNK signal transduction pathway, suggest that the impact of EpCAM expression on AP-1 transcription factor activity is mediated through the JNK pathway. Taken together, these results suggest that UPR mediated JNK/Ap-1 signal transduction has a significant role in the regulation of apoptosis in human ovarian cancer cells, and is a potential molecular target to enhance sensitivity of ovarian cancer to chemotherapy. PMID- 26261529 TI - Association between PD-1/PD-L1 and T regulate cells in early recurrent miscarriage. AB - In this study, we try to testify the relationship between the programmed cell death receptor-1 (PD-1)/programmed cell death ligand 1 (PD-L1) passway and Treg cells in maternal-fetal immune regulation through PD-1 blockade on lymphocytes of normal early pregnancy in vitro and investigation of the PD-1 and PD-L1 changes in early recurrent miscarriage patients. CD4+ CD25+ Treg cells and PD-1 (CD279) positive cell were detected in deciduas in early recurrent miscarriage patients by flow cytometry. And the normal early pregnant women were as controls. Meanwhile the mRNA level of PD-1 and molecular expression of PD-L1 in deciduas of early recurrent miscarriage patients were detected by real time RT-PCR test and Immunohistochemical staining respectively. Also through antibody blocking assay to block PD-1 on lymphocytes of normal early pregnancy in vitro further testify the relationship between PD-1/PD-L1 and Treg cells, the results were analyzed by flow cytometry. CD4+ CD25+ Treg cells decreased both in deciduas in RM (P < 0.05), and for all almost 100% Treg cells (CD4+ CD25+) expressed PD-1, but there was no difference between the PD-1 positive cells in decidual lymphocytes in RM and that in normal pregnancy women (P > 0.05). PD-L1 mRNA in deciduas decreased in RM (P < 0.001), but PD-1 mRNA no difference (P > 0.1). After PD-1 blockade there was no change in CD4+ CD25+ Treg cells percentage, while the CD4+ T cell percentage increased (P < 0.01), as well as the level of IFN-gamma in cells supernatant (P < 0.01). PD-1 blockade has a little influence on the number of Treg cells, and may lead to impaired Treg cells function, the decrease of PD-L1 may closely relates to the occurrence of early recurrent miscarriage and implies that Treg cells may through PD-1/PD-L1 pathway play a role of immunosuppression regulation, and the impairment of Treg cells function in recurrent early abortion cases may be due to PD-L1 decrease in deciduas or trophoblast cells rather than PD-1 change. PMID- 26261530 TI - Protective effect of RIP and c-FLIP in preventing liver cancer cell apoptosis induced by TRAIL. AB - TRAIL (TNF-related apoptosis-inducing ligand) is a member of the tumor necrosis factor superfamily that can induce tumor selective death by up-regulating death receptor 4 (DR4) and DR5 expression. The study aimed to explore the role of RIP and c-FLIP genes in TRAIL induced liver cancer cell HepG2 and Hep3B apoptosis and related mechanism. RIP and c-FLIP silenced HepG2 and Hep3B cell model were established through siRNA. Western blot was applied to test c-FLIP, RIP, DR4, DR5, FADD, Caspase-3/8/9, ERK1/2, and DFF45 protein expression. Caspase-8 kit was used to detect Caspase-8 expression. Flow cytometry was performed to measure cell apoptosis rate. Acid phosphatase method was applied to determine cell cycle. TRAIL had no significant effect on Caspase-3/8/9, DR4, DR5, ERK1/2, and DFF45 protein expression, but up-regulated c-FLIP and RIP protein expression and reduced FADD expression level. After treated by the chemotherapy drug mitomycin and adriamycin, c-FLIP and RIP expression decreased significantly, while FADD increased. After knockout c-FLIP and RIP gene, HepG2 and Hep3B cell apoptosis rate induced by TRAIL increased obviously. Meanwhile, cell subG1 percentage increased markedly and exhibited G1 phase growth retardation. In addition, after two kinds of gene knockout, Caspase-8 was activated and produce Caspase-3 P20 and P24, leading DFF45 appeared DNA fragment P17 and P25. c-FLIP and RIP can inhibit Caspase-8 activation and prompting HepG2 and Hep3B resistant to cell apoptosis induced by TRAIL. PMID- 26261531 TI - Protective effects of LM22A-4 on injured spinal cord nerves. AB - OBJECTIVE: The goal of this study was to elucidate the protection by and potential mechanisms of LM22A-4, a specific agonist of tyrosine kinase receptor B, against spinal cord injury (SCI). METHODS: Spinal cord trauma was induced by the application of vascular clips to the dura of mice via a four-level T7-T11 laminectomy. Thirty minutes after the injury, an abdominal injection of LM22A-4 (at dosages of 10 mg/kg and 15 mg/kg) or an equal volume of solvent was provided. Twenty-four hours after SCI, a Western blot was performed to examine the expression of p-TrkB, p-Akt, p-ERK, cleaved-caspase-3, and Bcl-2; a TUNEL assay and Nissl staining were performed to study apoptosis and the survival of neurons. In addition, another batch of mice was allowed to live for 14 days after the SCI treatment, during which the LM22A-4 was provided at the same time each day and the neurological function was assessed. RESULTS: Spinal cord injury in mice resulted in severe trauma characterized by tissue damage and apoptosis. Treatment of the mice with LM22A-4 (10 mg/kg) significantly reduced the degree of tissue injury (histological score) and apoptosis (TUNEL staining and caspase-3 and Bcl-2 expression) compared with vehicle treated group (P < 0.05). In a separate set of experiments, chronic treatment with LM22A-4 also significantly ameliorated the recovery of limb function (P < 0.05). CONCLUSION: This study provides an experimental evidence that LM22A-4 reduces the development of tissue injury associated with spinal cord trauma, and activation of the activity of TrkB may represent a novel approach for the therapy of spinal cord trauma. PMID- 26261532 TI - MicroRNA-200c overexpression inhibits chemoresistance, invasion and colony formation of human pancreatic cancer stem cells. AB - INTRODUCTION: Cancer stem cells (CSCs) are believed to be 'seed cell' in cancer recurrence and metastasis. MicroRNAs (miRNAs) have emerged as potential therapeutic candidates due to their ability to regulate multiple targets involved in tumor progression and chemoresistance. The goal of this study was to investigate the role of miRNA-200c (miR-200c) in regulating colony formation, invasion and chemoresistance of human pancreatic cancer stem cells (PCSCs). METHODS: PCSCs with CD24(+)CD44(+)ESA(+) as the marker was sorted from PANC-1 cell line by fluorescence activated cell sorter (FACS). Quantitative real-time PCR (qRT-PCR) assay was used to detect the expression of miR-200c in PCSCs and PANC-1 cells. Transfection of miR-200c mimic into PCSCs was performed to establish miR-200c over-expressed cells. The effects of overexpressing miR-200c on PCSCs were examined by cell colony forming, invasion and survival assays in vitro. RESULTS: Our data showed that CD24(+)CD44(+)ESA(+) PCSCs (0.5%) were isolated from PANC-1 cells. Expression of miR-200c was significantly reduced in PCSCs compared with PANC-1 cells. In addition, the capability of colony formation, invasion and chemoresistance were markedly increased in PCSCs than that in PANC-1 cells. Adverse results were obtained in miR-200c overexpressing PCSCs transfected with miR-200c mimic. CONCLUSION: Our study demonstrated that miR-200c overexpression could decrease colony formation, invasion and chemoresistance of PCSCs. It may become a new therapeutic target for gene therapy in patients suffered from pancreatic cancer. PMID- 26261533 TI - Establishment and identification of human primary lung cancer cell culture in vitro. AB - OBJECTIVE: To explore a simple and practical method for human primary lung cancer cells culture in vitro. METHODS: Tumor specimens from 6 lung cancer patients were isolated with collagenase digestion cultured in vitro. Then the characteristics of these cells were analyzed and identified by optical microscope observation, hematoxylin-eosin staining, immunocytochemistry, immunohistochemistry and tumor nude mice inoculation experiments, respectively. RESULTS: Except for the small cell lung cancer, the other 5 samples were successfully isolated and cultured. The cultured cells showed typical characteristics of malignant cells and positive for cytokeratin 7 and 19. Moreover, the cancer cells readily formed subcutaneous tumors in nude mice and the pathological images of the transplanted tumor were consistent with its tumor origin. CONCLUSION: The primary culture for human lung cancer cells can be successfully achieved with the method of collagenase digestion. PMID- 26261534 TI - MiR-126 regulated breast cancer cell invasion by targeting ADAM9. AB - Accumulating evidence has shown that microRNAs (miRNAs) deregulation is commonly observed in human malignancies and crucial to cancer metastasis. Herein, we demonstrated that miR-126 play a suppressor role in human breast cancer cells invasion through the direct repression of a disintegrin and metalloprotease 9 (ADAM9). MiR-126 expression was investigated in forty cases of breast cancer specimens by real-time PCR. Transwell assay was conducted to explore the effects of miR-126 on the invasion of human breast cancer cell lines. The impact of miR 126 overexpression on putative target ADAM9 was subsequently confirmed by Western blot analysis. Our results indicated that miR-126 expression was frequently down regulated in breast cancer specimens compared with adjacent normal tissues (P<0.05). Overexpression of miR-126 significantly reduced (P<0.05) the protein levels of ADAM9, further suppressed (P<0.05) breast cancer cell invasion in vitro. Meanwhile, knockdown of ADAM9 by small interfering RNA (siRNA) also inhibited (P<0.05) breast cancer cell invasion. Thus, our study revealed that miR 126 may act as a tumor suppressor via inhibition of cell invasion by downregulating ADAM9 in breast cancer development. PMID- 26261535 TI - Different doses of partial liver irradiation promotes hepatic regeneration in rat. AB - The aim of this study is to investigate whether partial liver irradiation promotes hepatic regeneration in rat. Left-half liver of rat was irradiated to 10 Gy, and the Right-half to 0, 5, 10 and 15 Gy, respectively. Then, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels were evaluated on 0 day, 15-day, 30-day, 45-day and 60-day after liver irradiation. Next, the serum HGF, NF-kappaB and TGF-beta1 levels were also analyzed on 60-day after liver irradiation. Lastly, the cyclinD1 protein expression was appraised by western blots on 60-day after liver irradiation. ALT, AST and ALP levels were reduced compared with that of controls. The serum HGF, NF kappaB and TGF-beta1 levels, and the cyclinD1 protein expression in liver irradiation group were increased compared with that of controls group. However, hepatic regeneration of higher dose-irradiated cirrhotic liver was triggered a more enhanced regeneration, compared with that of higher doses group. In summary, these results suggest that different doses of partial liver irradiation promotes hepatic regeneration in rat. PMID- 26261536 TI - Aberrant LRP16 protein expression in primary neuroendocrine lung tumors. AB - BACKGROUND: The Leukemia related protein 16 gene (LRP16) localized on chromosome 11q12.1, is an important estrogen-responsive gene and a crucial regulator for NF kB activation. LRP16 is frequently expressed in human cancers; however, the LRP16 gene remains unexplored in lung neuroendocrine tumors. The aim of this study was to investigate the role of LRP16 expression in primary lung neuroendocrine tumors. METHODS: lung neuroendocrine tumors were analyzed for LRP16 gene expression by two-step non-biotin immunohistochemical method. RESULTS: Fifty of ninety (55.6%) cases of neuroendocrine lung tumors tested were positive for LRP16 protein by immunohistochemistry. The expression of LRP16 was mainly located in cytoplasm and nucleus of tumor cells. LRP16 protein was corresponding to tumor type and clinical stage, as well as survival time. CONCLUSIONS: The results indicate that abnormal LRP16 expression is noted in neuroendocrine lung tumors and the expression can give insight into the pathogenesis of the disease. The LRP16 protein may serve as a potential marker in predicting prognosis of neuroendocrine lung tumors. PMID- 26261537 TI - Splenosis in gastric fundus mimicking gastrointestinal stromal tumor: a report of two cases and review of the literature. AB - Splenosis refers to heterotopic autotransplantation and implantation of splenic tissue following splenic trauma or surgery. Splenosis in gastric fundus is rare and difficult to diagnose, since splenosis has similar manifestation with gastrointestinal stromal tumor (GIST) under routine endoscopy examination. In this report, we present two quite rare case of splenosis. Both of their pre operative diagnose under endoscopic ultrasonography was considered as GIST. Finally, one in the abdominal cavity, adhering closely to the gastric fundus, measuring 20 mm * 15 mm, was resected by surgical operation, and one in the gastric fundus, measuring 20 mm * 20 mm, was resected by endoscopic surgery. The precise diagnosis of splenosis was distinct by post-operative histopathologic examination. In addition, we also made a mini review of previously published articles, in order to provide indication to solve future doubts in diagnosing and treating splenosis. PMID- 26261538 TI - Impact of E6-associated protein on the proliferation and invasion of prostate cancer cells in bone metastasis. AB - PURPOSE: To understand E6 associated protein (E6-AP)'s influence on prostate cancer cell proliferation and infiltration, thus providing the theoretical basis for developing therapeutic drugs for prostate cancer metastasis to the bone. METHODS: Electroporation was performed to introduce linear regulatory plasmid PrevTet-off-in and conjugative plasmid PrevTRE2-flag-E6AP into prostate cancer cell line to establish wild-type E6-AP over-expressing transgenic LNCaP cell line; Western blot assay was adopted to examine expression levels of E6-AP, mammalian target of rapamycin (mTOR), protein kinase B (Akt), and phosphoinositide 3-kinase (PI3K); PI3K inhibitor LY294002 was applied to all the cells and MTT assay was used to measure cell proliferation; Matrigel invasion chamber assay was adopted to detect cancer cell migration and invasion. RESULTS: Stably transfected LNCaP cells that over expressed E6-AP had higher expression levels of PI3K, Akt, and mTOR than control LNCaP cells; MTT assay showed that E6 AP-LNCaP cells were more responsive to the inhibitory effect of LY294002; Matrigel invasion chamber assay revealed increased cell crawling and adhesiveness of E6-AP-LNCaP cells. CONCLUSION: Stable over-expression of E6-AP increases the proliferation and invasion of LNCaP cells. PMID- 26261539 TI - High miR-196a and low miR-367 cooperatively correlate with unfavorable prognosis of high-grade glioma. AB - Identification of microRNAs (miRNAs) could be beneficial for the diagnosis and prognosis of glioma. Therefore, we attempted to identify and develop specific miRNAs as prognostic and predictive markers for glioma patients. We compared the expression profiles of 365 miRNAs between 4 glioblastomas (GBMs, WHO grade IV) and 4 anaplastic astrocytomas (AAs, WHO grade III) using miRNA qPCR Array. MiR 196a (P = 0.004, fold change = 289.86) and miR-367 (P = 0.044, fold change = 0.03) were identified as the most up-regulated and down-regulated miRNAs in GBMs compared with AAs, respectively. We subsequently examined miR-196a and miR-367 expression levels in an independent series of 63 gliomas including 50 GBMs and 13 AAs, as well as 10 non-neoplastic brain tissues, and statistically analyzed the associations between miRNA expression and clinicopathological characteristics and survivals of these glioma patients. MiR-196a and miR-367 showed significant increased and decreased expression in high-grade gliomas relative to non neoplastic brains, as well as in GBMs versus AAs, respectively. Additionally, high-miR-196a and low-miR-367 expression, alone or in combination, statistically correlated with aggressive clinicopathological features of gliomas. Furthermore, overall survivals of glioma patients with high-miR-196a, low-miR-367 and high-miR 196a/low-miR-367 expression tended to be shorter than the corresponding control groups (all P <= 0.001). Moreover, multivariate analysis indicated high-miR 196a/low-miR-367 as an independent prognostic indicator for glioma patients (P = 0.005, risk ratio = 1.8). Our results suggested that both high-miR-196a and low miR-367 expression may be associated with aggressive progression and unfavorable clinical outcome in glioma patients. And combination of high-miR-196a and low-miR 367 expression may be a novel biomarker in identifying a poor prognosis group of high-grade glioma. PMID- 26261540 TI - Overexpression of PROM1 (CD133) confers poor prognosis in non-small cell lung cancer. AB - The surface marker PROM1 is considered one of the most important marker of tumor initiating cells, and its high expression is believed to be an adverse prognostic factor in gliomas, medulloblastoma and in other malignancies. The aims of our research were to explore the expression profile of the PROM1 in non-small cell lung cancer (NSCLC) and to assess its possible role as a prognostic factor. The protein expression profiles were determined via immunohistochemical staining assay. The clinical prognostic values of protein expression were investigated with univariate and multivariate survival analysis. The quantitative variable PROM1 expression was dichotomized according to the best cutoff value obtained by the receiver operating characteristics (ROC) analysis. The protein level of PROM1 of NSCLC was higher compared with normal tissues, and the survival analysis demonstrated the positive membrane expression and combination of membrane/cytoplasm groups of PROM1 had worse prognosis than those negative expression groups. Also, multivariate Cox regression analysis showed membrane expression of PROM1 and lymph node invasion were the independent prognostic factors. The expression of PROM1 was significantly higher than normal tissue, and high levels of PROM1 membrane expression and combination of membrane/cytoplasm expression were associated with adverse prognosis. PMID- 26261541 TI - Qiliqiangxin improves cardiac function and attenuates cardiac remodeling in rats with experimental myocardial infarction. AB - OBJECTIVE: It has been reported that Qiliqiangxin (QL), a traditional Chinese medicine compound, could inhibit cardiac hypertrophy and remodeling, and improve cardiac function. However, whether and how it reverses cardiac remodeling in rats post myocardial infarction (MI) remains unknown. This study aims to explore related mechanisms linked with cardiac function improvement and attenuation of cardiac remodeling by QL in rats with experimental MI. METHODS: MI was induced by ligation of left anterior descending coronary artery (LAD) in male Sprague-Dawley rats. Rats with LVEF < 50% at four weeks after procedure were treated for another 6 weeks with placebo, QL and captopril. Echocardiography and plasma NT-proBNP were measured at the end of study, and histological studies were performed. Protein expressions of Neuregulin-1 (NRG-1), total-Akt, phospho-Akt (Ser473), hydroxy-HIF-1alpha (Pro564), VEGF, Bax, Bcl-2 and Caspase 3 were examined by Western blot. mRNA expression of NRG-1 and p53 was detected by real-time PCR. RESULTS: Compared with the placebo group, QL improved cardiac function, reduced left ventricular dimension, inhibited interstitial inflammation and fibrosis, increased neovascularization, and attenuated cardiomyocyte apoptosis. Meanwhile QL significantly upregulated the expression of HIF-1alpha, VEGF, enhanced phosphorylation of Akt, decreased the ratio of Bax/Bcl-2 and Caspase 3 expression. Furthermore, we observed upregulation of NRG-1 and downregulation of p53 after QL treatment. CONCLUSION: Our data suggest that the beneficial effects of QL on improving cardiac function and attenuating cardiac remodeling post MI are associated with angiogenesis enhancement and apoptosis inhibition, which may be mediated via activation of NRG-1/Akt signaling and suppression of p53 pathway. PMID- 26261542 TI - Expression and function of microRNA-188-5p in activated rheumatoid arthritis synovial fibroblasts. AB - Activated synovial fibroblasts in rheumatoid arthritis (RASF) play a critical role in the pathology of rheumatoid arthritis (RA). Recent studies suggested that deregulation of microRNAs (miRs) affects the development and progression of RA. Therefore, we aimed to identify de-regulated miRs in RASF and to identify target genes that may contribute to the aggressive phenotype of RASF. Quantitative real time PCR revealed a marked downregulation of miR-188-5p in synovial tissue samples of RA patients as well as in RASF. Exposure to the cytokine interleukine 1beta lead to a further downregulation of miR-188-5p expression levels compared to control cells. Re-expression of miR-188-5p in RASF by transient transfection significantly inhibited cell migration. However, miR-188-5p re-expression had no effects on glycosaminoglycan degradation or expression of repellent factors, which have been previously shown to affect the invasive behavior of RASF. In search for target genes of miR-188-5p in RASF we performed gene expression profiling in RASF and found a strong regulatory effect of miR-188-5p on the hyaluronan binding protein KIAA1199 as well as collagens COL1A1 and COL12A1, which was confirmed by qRT-PCR. In silico analysis revealed that KIAA1199 carries a 3'UTR binding site for miR-188-5p. COL1A1 and COL12A1 showed no binding site in the mRNA region, suggesting an indirect regulation of these two genes by miR-188 5p. In summary, our study showed that miR-188-5p is down-regulated in RA in vitro and in vivo, most likely triggered by an inflammatory environment. MiR-188-5p expression is correlated to the activation state of RASF and inhibits migration of these cells. Furthermore, miR-188-5p is directly and indirectly regulating the expression of genes, which may play a role in extracellular matrix formation and destruction in RA. Herewith, this study identified potential novel therapeutic targets to inhibit the development and progression of RA. PMID- 26261543 TI - MiR-218 inhibits HMGB1-mediated autophagy in endometrial carcinoma cells during chemotherapy. AB - Endometrial carcinoma is the most common gynecological malignancy among women worldwide. Although treatment for EC has improved with the introduction of Paclitaxel (Tax) chemotherapy, the majority of patients will develop resistance to the treatment, leading to poor prognosis. One of the causes of chemoresistance is the increased ability to undergo autophagy. In this study, we identified that miR-218 was significantly down-regulated in Tax-resistant EC cells compared to the non-drug resistant cell lines, and overexpression of miR-218 sensitized paclitaxel resistant EC cells to paclitaxel. Moreover, we demonstrated that miR 218 directly binds to the 3'-UTR of HMGB1 gene. HMGB1 was upregulated in paclitaxel resistant EC cells, it mediated autophagy and contributed to chemotherapy resistance in endometrial carcinoma in vitro. HMGB1-mediated autophagy could be suppressed by miR-218 overexpression in Tax resistant EC cells. In summary, we determined the targeting role of miR-218 to HMGB1 and the regulation of miR-218 on the HMGB1-mediated cell autophagy during chemotherapy resistance in endometrial carcinoma cells. These results reveal novel potential role of miR-218 against chemotherapy resistance during the treatment of endometrial carcinoma. PMID- 26261544 TI - Peroxiredoxin 4 as an independent prognostic marker for survival in patients with early-stage lung squamous cell carcinoma. AB - OBJECTIVES: Peroxiredoxin 4 (Prx 4) is a newly emerging antioxidant protein that has been studied in several human cancers. Recently, it was revealed that Prx 4 is highly expressed in human lung cancer and is needed for the promotion of lung cancer progression in vitro. However, there are no clinical data regarding the association of Prx 4 and prognosis in lung cancer. MATERIALS AND METHODS: The Prx 4 expression state as a prognostic indicator was assessed by immunohistochemical staining in 142 patients with stage II non-small cell lung cancer (NSCLC) who had undergone curative surgery between 2006 and 2010. The association between the degree of Prx 4 expression and several clinicopathologic parameters was then evaluated by statistical analyses. RESULTS: The degree of Prx 4 expression was associated with histology and recurrence in the overall NSCLC patient group, with the proportion of patients with positive Prx 4 expression significantly higher for the adenocarcinoma subtype (39/70, 56%) than the squamous cell carcinoma subtype (23/72, 32%) (P = 0.004). However, when subgroup analyses according to histopathology were performed in terms of recurrence, positive Prx 4 expression was significantly correlated with higher recurrence rates (P = 0.003) and shorter disease-free survival (DFS) (P = 0.003, hazard ratio = 3.910) in patients with squamous cell carcinoma. In contrast, no meaningful relationship was observed between the level of Prx 4 expression and DFS in the adenocarcinoma subgroup. CONCLUSION: Positive Prx 4 expression is significantly correlated with recurrence and shorter DFS in patients with early-stage lung squamous cell carcinoma. PMID- 26261545 TI - Calcium alginate enhances wound healing by up-regulating the ratio of collagen types I/III in diabetic rats. AB - Calcium alginate has been proved to favor the skin ulcer healing and collagen synthesis was a critical factor for the wound closure. The present study was to elucidate the mechanism of calcium alginate on the diabetes skin ulceration. Calcium alginate dressing was applied daily on the full-thickness exercising wound created on the back of diabetic rat model as Alg-group (n=6), and the vaseline dressing was used as control (n=6). Rats were respectively sacrificed and the wound tissues were removed and used for the evaluation of various biochemical analysis contained collagen (type I and III) by Western blotting and hydroxyproline level changes by ELISA assay at 3 d, 7 d and 14 d after wounding. The expression of skin collagen I in Alg-group was enhanced from day 3 (0.66 +/- 0.25 vs. 0.42 +/- 0.09, P<0.05) to day 14 (1.09 +/- 0.14 vs. 0.78 +/- 0.16, P<0.05). However, no significant difference of collagen III expression was found between two groups during wound healing (P>0.05). And the ratio of collagen I/III in Alg-group was greater than that of Vas-group at day 7 (1.07 +/- 0.31 vs. 0.77 +/- 0.11, P<0.05) and 14 (1.18 +/- 0.30 vs. 0.83 +/- 0.14, P<0.05). The hydroxyproline level in skin homogenate of Alg-group was higher than that of Vas group from day 3 (30.29 +/- 0.92 ng/ml vs. 27.52 +/- 0.83 ng/ml, P<0.05) to day 14 (89.58 +/- 4.97 ng/ml vs. 79.30 +/- 4.42 ng/ml, P<0.05). Calcium alginate accelerates the process of wound healing through improving type I collagen synthesis and increasing ratio of collagen I/III in diabetic rats. PMID- 26261547 TI - The role of tumor-associated macrophages in breast carcinoma invasion and metastasis. AB - The main purpose of this study was to investigate the infiltration of tumor associated macrophages (TAMs) in normal and malignant breast tissue and the draining lymph nodes, and to explore its effect on breast cancer invasion and metastasis. The infiltration densities of TAMs was observed using immunohistochemical staining of CD68 in 100 cases of breast cancer specimens and its paired adjacent non-cancer breast tissues and draining lymph modes, and then to evaluate the relation of TAMs to various clinicopathological features including patients prognosis in breast carcinoma. We observed the infiltration densities of TAMs were significantly higher in breast carcinoma tissue than in adjacent normal tissue and significantly higher in much larger size and higher stage cases. Furthermore, infiltration densities of TAMs have negative correlation with the 5-year survival rates of breast cancer patients. But in matched lymph-nodes, the infiltration densities of TAMs were significantly lower in cancerous metastatic lymph-node samples than in non-metastatic one. Therefore, our data suggests that TAMs infiltration in primary tumor promote invasion and lymphatic metastasis of breast cancer and have negative correlation with patients prognosis in breast cancer, but in lymph-node TAMs may play another role and need further study in the future. PMID- 26261546 TI - MiR-1228 promotes breast cancer cell growth and metastasis through targeting SCAI protein. AB - Breast cancer is the most common cancer in women around the world. However, the molecular mechanisms underlying breast cancer pathogenesis are only partially understood. Here, in this study, we found that miR-1228 was up-regulated in breast cancer cell lines and tissues. Ectopic expression of miR-1228 mimics leads to promoted cell growth, invasion and migration. Using bioinfomatic analysis and 3'UTR luciferase reporter assay, we determined SCAI can be directly targeted by miR-1228, which can down-regulate endogenous SCAI protein level. Furthermore, our findings demonstrate that SCAI was down-regulated in breast cancer cell lines and tissues. Rescue experiment demonstrated that miR-1228 promoted cell growth is attenuated by over-expression of MOAP1 and miR-1228 promoted cell invasion and migration can be attenuated by over-expression of SCAI. Taken together, this study provides evidences that miR-1228 serves as an oncogene to promote breast cancer proliferation, invasion and migration, which may become a critical therapeutic target for breast cancer treatment. PMID- 26261548 TI - Suppressive effect of beta, beta-dimethylacryloyl alkannin on activated dendritic cells in an imiquimod-induced psoriasis mouse model. AB - PURPOSE: To investigate the effect of beta, beta-dimethylacryloyl alkannin, a main component of Lithospermum erythrorhizon, on activated dendritic cells (DCs) in a psoriasis mouse model. METHODS: BALB/c mice were used to establish the animal model for psoriasis-like skin lesion; alkannin at 10 mg/kg (high), 5 mg/kg (medium), 2.5 mg/kg (low), respectively, were intragastrically administered. Psoriasis area and severity index (PASI) was used to evaluate the skin lesions. Histological changes, the thickness of epidermis, and the quantity of interleukin (IL)-23 in skin lesion were measured. In in vitro experiments, mononuclear cells in peripheral blood from healthy people were isolated, and monocytes were obtained. DCs with a mature state in differentiation and function were obtained through in vitro induction with several cytokines, and identified by flow cytometry. The influence of DCs on proliferation of allogenic lymphocytes was analyzed. The influence of alkannin on messenger ribonucleic acid (mRNA) expression of pro-inflammatory factors by mature DCs was evaluated using reverse transcriptase polymerase chain reaction. RESULTS: Mice treated with alkannin at varying concentration showed obvious remission in psoriasis-like skin lesion compared to control group, with decreased PASI score, obviously reduced vertical thickness of epidermis. Besides, alkannin treatment decreased the expression of IL-23 in skin lesion. Alkannin (12.5 MUg/mL) suppressed the ability of DCs to stimulate the proliferation of allogenic lymphocytes, and suppressed the expression and secretion of IL-6, IL-12 p40, IL-23, IL-1beta, tumor necrosis factor-alpha mRNA and proteins, respectively. CONCLUSIONS: beta, beta dimethylacryloyl alkannin could suppress the function of activated DCs in imiquimod-induced psoriasis mouse model. PMID- 26261549 TI - Effects of targeted nano-delivery systems combined with hTERT-siRNA and Bmi-1 siRNA on MCF-7 cells. AB - The aim of this study was to evaluate the efficiency of a targeted siRNA nano delivery system to silence the expression of Bmi-1 and hTERT, and to verify the toxicity of this delivery system in MCF-7 breast cancer cells. The most effective Bmi-1 siRNA and hTERT siRNA sequences were selected using RT-PCR and Western blotting. The polyethyleneimine (PEI)/siRNA nano-condensate was synthesized using PEI and modified using an NGR peptide fragment for targeting to tumor cells. The vector morphology, particle size and zeta potential were observed using an atomic force microscope and a laser particle size analyzer. The MCF-7 breast cancer cell line was transfected with the vector, and cytotoxicity was tested by MTT assays. The transfection efficiency was evaluated by qRT-PCR and Western blotting. Changes in gene expression and apoptosis rate were measured by flow cytometry. The size of LPN carrier and the condensate particle was between 100 and 200 nm and the potentials were close to neutral. There was maximum transfection efficiency and no significant increase in toxicity at 15 pmol/L. Bmi-1 and hTERT expression decreased, but the inhibition rate increased in the hTERT siRNA group, the hTERT+Bmi-1 siRNA group and the hTERT+Bmi-1 siRNA group compared with the scrambled siRNA group and the control group. Moreover, the hTERT+Bmi-1 siRNA group had the highest level of gene silencing. The complex, composed of Lipo, PEI and siRNA, is low toxicity and efficient transfection vectors. The expression level of Bmi-1 and hTERT was decreased by the gene silencing of either Bmi-1 or hTERT, but the effects were more significant when both were silenced simultaneously. PMID- 26261550 TI - HMGB1 is activated in type 2 diabetes mellitus patients and in mesangial cells in response to high glucose. AB - Diabetic nephropathy (DN) is one of the most devastating complications of diabetes, leading the cause of end-stage renal disease (ESRD). And investigations into mechanisms underlying renal inflammation may provide new insight into novel therapeutic targets for patients with DN. However, little is known about the promotion of inflammation in DN. In the present study, we examined the promotion by high glucose to High-mobility group box-1 (HMGB1) in patients with type 2 diabetes mellitus or in renal mesangial SV40 MES 13 cells. Results demonstrated that high glucose promoted the pre-inflammatory cytokines, such as TNF-alpha, IL 1beta and IL-6 in patients with T2DM or in SV40 MES 13 cells. And the serum HMGB1 was also upregulated in T2DM patients, correlating with serum IL-6 and TNFalpha. The in vitro results indicated that HMGB1 mediated the D-glucose-induced pro inflammatory cytokines in mesangial cells. And the NF-kappaB signaling pathway involved in the promotion of pro-inflammatory cytokines by D-glucose. In summary, the present study indicated that HMGB1 was significantly promoted by the glucose in vivo or in vitro, in an association with an upregulation of pro-inflammatory cytokines, via activating NF-kappaB signaling pathway. And the strategy of HMGB1 inhibition reduced the upregulation of pro-inflammatory cytokines in response to high glucose, via inhibiting the NF-kappaB signaling pathway. It implies the regulatory role of HMGB1 in the inflammatory responses in DN. PMID- 26261551 TI - Local blockage of EMMPRIN impedes pressure ulcers healing in a rat model. AB - Excessive extracellular matrix degradation caused by the hyperfunction of matrix metalloproteinases (MMPs) has been implicated in the failure of pressure ulcers healing. EMMPRIN, as a widely expressed protein, has emerged as an important regulator of MMP activity. We hypothesize that EMMPRIN affects the process of pressure ulcer healing by modulating MMP activity. In the rat pressure ulcer model, the expression of EMMPRIN in ulcers detected by Western blot was elevated compared with that observed in normal tissue. To investigate the role of EMMPRIN in regulating ulcer healing, specific antibodies against EMMPRIN were used via direct administration on the pressure ulcer. Local blockage of EMMPRIN resulted in a poor ulcer healing process compared with control ulcers, which was the opposite of our expectation. Furthermore, inhibiting EMMPRIN minimally impacted MMP activity. However, the collagen content in the pressure ulcer was reduced in the EMMPRIN treated group. Angiogenesis and the expression of angiogenic factors in pressure ulcers were also reduced by EMMPRIN local blockage. The results in the present study indicate a novel effect of EMMPRIN in the regulation of pressure ulcer healing by controlling the collagen contents and angiogenesis rather than MMPs activity. PMID- 26261552 TI - CXCR4 inhibitor attenuates allergen-induced lung inflammation by down-regulating MMP-9 and ERK1/2. AB - Chemokine (C-X-C motif) ligand 12 (CXCL12) and its receptor chemokine receptor 4 (CXCR4) have been recognized to play a crucial role in the pathogenesis of bronchial asthma, but the underlying molecular mechanisms are yet to be fully addressed. In the present report we demonstrated that CXCL12/CXCR4 signaling mediates allergic airway inflammation through induction of matrix metalloproteinase 9 (MMP-9) in a murine asthmatic model. We noted that administration of AMD3100, a specific CXCR4 antagonist, significantly attenuated OVA-induced asthmatic responses along with reduced epithelial MMP-9 expression. Our studies in a bronchial epithelial cell line, 16HBE cells, further revealed that CXCL12/CXCR4 signaling synergizes with IL-13 to enhance epithelial MMP-9 expression. Our mechanistic studies demonstrated that CXCL12/CXCR4 enhances epithelial MMP-9 expression by inducing ERK1/2 expression and activation. Together, these studies would bring novel insight into the understanding for the role of CXCL12/CXCR4 signaling in asthmatic responses during the course of bronchial asthma development. PMID- 26261553 TI - Lipoxin A4 promotes ABCA1 expression and cholesterol efflux through the LXRalpha signaling pathway in THP-1 macrophage-derived foam cells. AB - Adenosine triphosphate-binding cassette transporter A1 (ABCA1) is a crucial cholesterol transporter and plays a central role in the high density lipoproteins (HDL) cholesterol metabolism and lipid clearance from the foam cell. Lipoxin A4 (LXA4) is an endogenous lipid mediator that requires cell-cell interaction or cell-platelet interaction for its synthesis. The roles of LXA4 on inflammatory responses are well described, while its effects on mediating ABCA1 and underlying mechanisms remain unclear. In this study, we showed that LXA4 significantly increases expression of ABCA1 and LXRalpha in a dose-dependent manner in THP-1 macrophage-derived foam cells. Cellular cholesterol content was decreased while cholesterol efflux was increased by LXA4 treatment. However, after short interfering RNA of LXRalpha, the effects of LXA4 on ABCA1 expression and cholesterol metabolism were significantly abolished. These results provide evidence that LXA4 increases ABCA1 expression and promotes cholesterol efflux through LXRalpha pathway in THP-1 macrophage-derived foam cells. PMID- 26261554 TI - Desmocollin 3 mediates follicle stimulating hormone-induced ovarian epithelial cancer cell proliferation by activating the EGFR/Akt signaling pathway. AB - Follicle-stimulating hormone (FSH) is associated with the pathogenesis of ovarian cancer. We sought to explore whether desmocollin 3 (Dsc3) mediates FSH-induced ovarian epithelial cancer cell proliferation and whether the EGFR/Akt signaling pathway may be involved in this process. Dsc3 positivity in ovarian tissue specimens from 72 patients was assessed by immunohistochemistry. The positive expression rates of Dsc3 were similar in ovarian cancer tissues (24/31:77.4%) and borderline ovarian tumor tissues (18/22:81.8%) (P>0.05), but were significantly higher in these cancerous tissues than in benign ovarian cyst tissues (3/19:15.8%) (P<0.05). Consistently, the expression of Dsc3 in four out of five ovarian cancer cells (HO8910, Skov3ip, Skov and Hey cells, but not ES-2 and in borderline ovarian MCV152 tumor cells was higher than in the immortalized ovarian epithelial cell line, Moody. FSH up-regulated the expression of Dsc3 and EGFR in a dose- and time-dependent manner. Furthermore, a converse relationship between the expression of Dsc3, EFGR and PI3K/Akt signaling was elucidated using RNA interference and PI3K/Akt inhibitor in the absence and presence of FSH. A role for these proteins in FSH-induced cell proliferation was verified, highlighting their interdependence in mediating ovarian cancer cell function. These results suggest that Dsc3 can mediate FSH-induced ovarian cancer cell proliferation by activating the EGFR/Akt signaling pathway. PMID- 26261555 TI - Expression of CD44 in pancreatic cancer and its significance. AB - BACKGROUND: CD44 is a potentially interesting prognostic marker and therapeutic target in pancreatic cancer. The expression of CD44 has been reported to correlate with poor prognosis of pancreatic cancer in most literatures. The purpose of this study is to investigate the roles of CD44 in pancreatic caner, and their correlation with the prognosis of pancreatic cancer patients. METHODS: 67 pancreatic cancer samples were collected in Xinhua hospital affiliated to Shanghai Jiaotong University dating from Jan 2010 to Dec 2012. Immunohistochemistry was applied to test the expression of CD44 in pancreatic cancer. The clinical data of the patients were collected including their gender, age, the histology and location, lymph node metastasis and so on. The correlation between the CD44 expression and the clinicopathological factors of patients with pancreatic cancer was analyzed by the software SPSS 13.0. We devise and synthesis of effectively interference of shRNA sequence of CD44, which was transefected to the pancreatic cancer cells PANC-1. Colony formation assay, cell migration assays and western blot were performed. RESULTS: The positive rates of CD44 expression in pancreatic samples were 73.1% (49/67). Univariate analysis showed that there were a significant differences between the CD44 expression and the pancreatic cancer' T staging, TNM staging, lymph node metastasis, the differentiation degree, tumor location (P < 0.05). The Cox proportional hazards model showed that differentiation, CD44 expression and nerve invasion were independent prognostic factors. Knockdown of CD44 expression in pancreatic cancer cells led to decreased cellular proliferation and migration ability, accompanied by downregulation of p ERK and p-AKT. CONCLUSION: CD44 were related to the distant metastasis and aggressive malignant behaviors of pancreatic cancer. CD44 may regulate tumorigenesis and cancer metastasis partially via PI3K/AKT or MAPK/ERK regulatory pathway. PMID- 26261556 TI - JAK2/STAT3 pathway mediating inflammatory responses in heatstroke-induced rats. AB - Heatstroke not only directly induces cell injury, but also causes large amounts of inflammatory mediators release and cells with extensive biological activities to induce a systemic inflammatory response and immune dysfunction. This study aimed to observe the effects of JAK2 inhibitor AG490 on the brain injury and inflammatory responses of rats with systemic heatstroke. Under the light microscope, the hippocampus tissues of rat with heatstroke were edema and apoptotic rate was increased. Up-regulation of malondialdehyde (MDA), nitric oxide synthase (iNOS), reactive oxygen species (ROS) and down-regulation of superoxide dismutase (SOD) were also found after heatstroke in rats, which compared with that of the control group. Heatstroke induced inflammation factors secretions and up-regulated levels of matrix metallopeptidase 2 and 9 (MMP2 and MMP-9) and systemic inflammatory response molecules including intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-beta 1 (TNF-beta1) and cyclooxygenase-2 (COX-2). However, the JAK2 inhibitor AG490 was significantly attenuated the brain injury and inflammatory responses induced by heatstroke in rats. The survival time of heatstroke rats showed that AG490 notably lived longer than heatstroke rats without AG490 treatment. These findings suggest that AG490 may prevent the occurrence of heatstroke via inhibiting the JAK2/STAT3 pathway and the systemic inflammatory responses. PMID- 26261557 TI - Protective effects of luteolin against cognitive impairment induced by infusion of Abeta peptide in rats. AB - Luteolin can be found in many traditional Chinese medicines, it's a falconoid compound derived from Lonicera japonica Thunb. This study aims to investigate the neuroprotective effects of luteolin against cognitive impairment induced by amyloid-beta (Abeta) peptide and the underlying mechanisms in rats. The animal behavioral tests showed that luteolin could ameliorate Abeta-induced learning and memory impairment. In hippocampal tissue, the activity of choline acetyl transferase (ChAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH Px) increased after treated by luteolin. Luteolin also reversed the increased activity of acetylcholine esterase (AchE). In hippocampi homogenate, the content of acetylcholine (Ach) increased, but malondialdehyde (MDA) reduced. Moreover, luteolin can increase Bcl-2/Bax ratio. This study demonstrated that luteolin could protect Alzheimer's disease (AD) rats against Abeta-induced cognitive impairment through regulating the cholinergic system and inhibiting oxidative injuries. The results suggesting that luteolin may have potential as a therapy for AD. PMID- 26261558 TI - Effect of metformin on Schwann cells under hypoxia condition. AB - Metformin, which is the first-line drug for the treatment of diabetes mellitus type 2, has been proved to possess beneficial effects on nerve regeneration in many studies. However, the underlying mechanism is currently unclear. The present study was designed to investigate the potential beneficial effect of metformin on SCs under hypoxia condition, which is a biological process at the injury site. The cell number and cell viability of SCs were examined using fluorescence observation and MTT assay. The migration of SCs was evaluated using a Transwell chamber. The expression and secretion of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF) and neural cell adhesion molecule (N-CAM) in SCs were assayed by RT-PCR and ELISA method. The results showed that metformin could help SCs recover from hypoxia injury and inhibit hypoxia-induced apoptosis. In addition, metformin could partially reverse the detrimental effect of hypoxia on cell number, viability, migration and adhesion. Metformin is also capable of maintaining the biological activities of SCs after hypoxia injury, such as increasing the expression and secretion of BDNF, NGF, GDNF, and N-CAM. Further studies showed that pre incubation with AMPK (5'-AMP-activated protein kinase) inhibitor Compound C might partially inhibit the effect of metformin mentioned above, indicating the possible involvement of AMPK pathway in the beneficial effects of metformin on peripheral nervous system. In conclusion, metformin is capable of alleviating hypoxia-induced injury to SCs and AMPK pathway might be involved in this process. PMID- 26261559 TI - FOXM1-LDHA signaling promoted gastric cancer glycolytic phenotype and progression. AB - The oncogenic transcription factor forkhead box protein M1 (FOXM1) plays critical roles in gastric cancer (GC) development and progression. However, the underlying mechanisms has not fully demonstrated. Lactate dehydrogenase A (LDHA) is widely overexpressed in a series of cancers and is one of the two subunits of Lactate dehydrogenase (LDH), which is the key glycolytic enzyme and catalyzes the interconversion of pyruvate and lactate. In this study, we characterized the regulation of aerobic glycolysis by FOXM1 via transactivation of LDHA in GC. We found that LDHA was overexpressed GC cells, and the expression of LDHA was transcriptionally regulated by FOXM1. Furthermore, FOXM1 regulated GC cells glycolytic phenotype, proliferation, migration and invasion via LDHA. Thus, FOXM1 LDHA signaling functioned as a stimulator of glycolysis and promoted GC progression. PMID- 26261560 TI - APPL1 acts as a protective factor against podocytes injury in high glucose environment. AB - APPL1, an intracellular adaptor protein, takes part in numerous metabolic reactions. Although APPL1 plays a key role in glucose metabolism via adiponectin pathway and has been proved associated with type 2 diabetes, little is known about its role in diabetic nephropathy. To explore the role of APPL1 in diabetic nephropathy, we upregulated the expression of APPL1 in cultured mouse podocytes by adenovirus infection and tested the effects of APPL1 overexpression in podocytes treated with high glucose. Here, a mouse podocyte cell line (generated from H-2Kb-tsA58 immortmouse) was cultured and divided into four groups: Group 1 (normal glucose, NG), Group 2 (high glucose, HG), Group 3 (HG and infected with control adenovirus) and Group 4 (HG and infected with Ad-APPL1). Cell vitality of Group 4 is significantly higher than Group 2, but notably lower than Group 1 (P<0.01). The apoptosis rate of Group 4 was much lower (P<0.01) than Group 2 and Group 3. A decrease in phase G0/G1 and an increase in phase S was observed in Group 4 compared with Group 2 (P<0.01). These data suggested the protective role of APPL1 overexpression in high glucose condition. Moreover, the levels of Nephrin, AMPK and p-AMPK were decreased by high-glucose treatment, but increased by APPL1 overexpression. In conclusion, in the experimental high glucose condition, APPL1 acts as a protective factor against podocytes injury through regulating AMPK signaling, and may be a new therapy target for diabetic nephropathy. PMID- 26261561 TI - HAEC in the treatment of brain hemorrhage: a preliminary observation in rabbits. AB - OBJECTIVE: This study aimed to evaluate the therapeutic potential of human amniotic epithelial cell (HAEC) transplantation in the management of brain hemorrhage in an animal model. METHODS: New Zealand white rabbits were induced to develop cerebral hemorrhage through autologous blood injection. Animals with confirmed brain hemorrhage were randomized to receive transplantation of, respectively, vehicle (n=15) and primary HAECs (n=15) that were expressing embryonic stem cell- and neuron-specific markers and were transfected with a retroviral vector carrying the green fluorescent protein (GFP). Behavioral and histological changes, survival of transplanted HAECs, and expression of glial fibrillary acidic protein (GFAP) and MAP-2 in transplanted perifocal tissue were assessed at various time points after transplantation. RESULTS: At 2-3 weeks after transplantation, walking, body weight-supporting and movement coordinating capacities of limbs were improved mostly level II-III hemorrhage lesion cases in HAEC transplantation group but mostly in level I-II hemorrhage lesion cases in the vehicle control group. The Tarlov scores were significantly difference between the two groups (P<0.05). GFAP- and MAP-2-positive cells were observed in the neural tissue in animals transplanted with hAECs but not in animals in the control group (P<0.05). CONCLUSION: These preliminary observations suggest that hAEC transplantation possess both embryonic stem cell features and a neuron differentiation potential and thus may offer a promising treatment for hemorrhage associated neurological damage. PMID- 26261562 TI - Angelica Sinensis attenuates inflammatory reaction in experimental rat models having spinal cord injury. AB - This study was aimed to evaluate the effect of Angelica Sinensis on experimental rat models in which spinal cord injury was induced by studying different factors. Different factors causing inflammation play a key role in pathophysiology of SCI. Here three groups of rats (n=15, each was used). These included a sham control group where only laminectomy was performed, SCI group where SCI was induced and AS/SCI group where although SCI was induced but Angelica Sinensis was also administered to study its effect and draw a comparison with control. The expression of I-kBalpha and NF-kB p65 was also studied using western blotting and after recording optical density (OD) values of western blots. MPO activity was used to measure the effect of 20 mg/kg Angelica Sinensis. The levels of proinflammatory cytokines TNF-alpha, IL-1beta and IL-6 were also studied. As compared with SCI group and sham control it was observed that Angelica Sinensis significantly reduced the expression of I-kBalpha and NF-kB p65, (P<0.05), while MPO activity was also significantly reduced. Proinflammatory cytokine level was also reduced in treated group as compared to both other groups. On the basis of this study we concluded that the use of 20 mg/kg Angelica Sinensis in rat models can attenuate the secondary damage caused by SCI and thus help in controlling the pathology of SCI in rats. PMID- 26261563 TI - N-terminal pro-B-type natriuretic peptide as a marker of blunt cardiac contusion in trauma. AB - Cardiac contusion is usually caused by blunt chest trauma and, although it is potentially a life-threatening condition, the diagnosis of a myocardial contusion is difficult because of non-specific symptoms and the lack of an ideal test to detect myocardial damage. Cardiac enzymes, such as creatine kinase (CK), creatine kinase MB fraction (CK-MB), cardiac troponin I (cTn-I), and cardiac troponin T (cTn-T) were used in previous studies to demonstrate the blunt cardiac contusion (BCC). Each of these diagnostic tests alone is not effective for diagnosis of BCC. The aim of this study was to investigate the serum heart-type fatty acid binding protein (h-FABP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), CK, CK-MB, and cTn-I levels as a marker of BCC in blunt chest trauma in rats. The eighteen Wistar albino rats were randomly allocated to two groups; group I (control) (n=8) and group II (blunt chest trauma) (n=10). Isolated BCC was induced by the method described by Raghavendran et al. (2005). All rats were observed in their cages and blood samples were collected after five hours of trauma for the analysis of serum h-FABP, NT-pro BNP, CK, CK-MB, and cTn-I levels. The mean serum NT-pro BNP was significantly different between group I and II (10.3 +/- 2.10 ng/L versus 15.4 +/- 3.68 ng/L, respectively; P=0.0001). NT-pro BNP level >13 ng/ml had a sensitivity of 87.5%, a specificity of 70%, a positive predictive value of 70%, and a negative predictive value of 87.5% for predicting blunt chest trauma (area under curve was 0.794 and P=0.037). There was no significant difference between two groups in serum h-FABP, CK, CK-MB and c Tn-I levels. A relation between NT-Pro BNP and BCC was shown in this study. Serum NT proBNP levels significantly increased with BCC after 5 hours of the blunt chest trauma. The use of NT-proBNP as an adjunct to other diagnostic tests, such as troponins, electrocardiography (ECG), chest x-ray and echocardiogram may be beneficial for diagnosis of BCC. PMID- 26261564 TI - Mandible ameloblastoma with lung metastasis: a rare case report. AB - BACKGROUND: The ameloblastoma is the most common odontogenic epithelial tumor, which belong to benign neoplasms that present a painless course, and usually occur in the oromaxillo-facial region. Although the histopathological manifestation of ameloblastoma is benign, it has unique biological behavior, for example local invasion and recurrence repeatedly. A few case of ameloblastoma was locally aggressive growth, and rarely metastasis to other tissue, for example the lungs, lymph nodes, and spine. CASE REPORT: A 64-year-old Chinese man, diagnosed with metastatic ameloblastoma, was treated with palliative chemotherapy consisting of cyclophosphamide, doxorubicin, and cisplatin for six cycles, and radiotherapy for 50 Gy after the last cycle chemotherapy. During the surveillance CT scan after the therapy, the tissues of the tumor were nearly complete response. CONCLUSION: The purpose of this study was to report a case of a patient with a right mandible ameloblastoma that recurred repeatedly and metastasized into bilateral lung. After the chemotherapy and radiotherapy, the tissues of the tumor were nearly complete response. This case is interesting because it investigated the diagnosis and treatment of the malignancy ameloblastoma, as this may help diagnose and treatment for clinician to the metastatic ameloblastoma. PMID- 26261565 TI - Bacterial extract OM-85 BV protects mice against experimental chronic rhinosinusitis. AB - OBJECTIVES: To investigate the therapeutic effects of OM-85 BV as an adjunctive treatment on experimental chronic rhinosinusitis (CRS) in mice. METHODOLOGY: Female BALB/c mice aged 8-12 weeks were sensitized and administrated by intranasal Aspergillus fumigatis (AF) three times per week for 1 week, 3 weeks, 2 months and 3 months (n = 10 each time point). The mice were randomly and equally assigned to four groups: normal control group, model group, OM-85-BV plus amoxicillin group, and isolated amoxicillin group. Inflammatory changes were determined by hematoxylin-eosin (HE) staining. The expression levels of suppressor of cytokine signaling (SOCS) 1, SOCS3, tumor necrosis factor (TNF) alpha, and interferon (IFN)-gamma in samples were assessed by using real-time PCR (RT-PCR) and Western blotting. RESULTS: There were significantly inflammatory and structural changes between the model and other groups. Compared to the model group, the mRNA expression levels of SOCS1, SOCS3, TNF-alpha, and IFN-gamma were significantly decreased in OM-85-BV plus amoxicillin group and isolated amoxicillin group, along with the protein levels. CONCLUSION: The bacterial extract OM-85 BV is a low-cost alternatively adjunctive drug to treat CRS with simple oral administration, good safety, and few side effects. PMID- 26261566 TI - The role of high mobility group box 1 (HMGB-1) in the diabetic retinopathy inflammation and apoptosis. AB - Diabetic Retinopathy (DR) is one of the most common complications of the late phase diabetes, and also a common cause of blindness. High mobility group box 1 (HMGB-1) is considered to be an inflammatory mediator in the late phase that promotes inflammation and neovascularization in diabetes. Therefore, this paper discussed the role of HMGB-1 in diabetic retinopathy inflammation and neovascularization. 96 adult SD rats were randomly divided into control and diabetes group. The diabetic rat model was established by intraperitoneal injection of streptomycin (0.1 mol/L). Western blot was applied to determine HMGB 1 and its receptor RAGE and TLR2 protein expression in the serum. TUNEL was used to detect retinal apoptosis. Immunofluorescence was performed to test HMGB1 protein expression in retina. HBGM-1 and RAGE expression in diabetic rat retina was significantly higher than the control (P < 0.05), while TLR2 expression was lower (P < 0.05). TUNEL detection showed that diabetic rat retinal cells presented obviously higher apoptosis rate (P < 0.05). Immunofluorescence test revealed that HMGB1 largely expressed in the diabetic rat retinal cells (P < 0.05). HMGB1 may involve in the pathogenesis of diabetic retinopathy by binding with RAGE receptor to accelerate rat retinal cells apoptosis. PMID- 26261567 TI - Effects of hydrogen sulfide on high glucose-induced glomerular podocyte injury in mice. AB - The aim of this study was to assess the effects of hydrogen sulfide on high glucose-induced mouse podocyte (MPC) injury and the underlying mechanisms. Mouse podocytes were randomly divided into 4 groups, including high glucose (HG), normal glucose (NG), normal glucose + DL-propargylglycine (PPG), and high glucose + NaHS (HG + NaHS) groups for treatment. Then, ZO-2, nephrin, beta-catenin, and cystathionine gamma-lyase (CSE) protein expression levels were determined by western blot. We found that high glucose significantly reduced nephrin, ZO-2, and CSE expression levels (P<0.05), and overtly elevated beta-catenin amounts (P<0.05), in a time-dependent manner. Likewise, PPG at different concentrations in normal glucose resulted in significantly lower CSE, ZO-2, and nephrin levels (P<0.05), and increased beta-catenin amounts (P<0.05). Interestingly, significantly increased ZO-2 and nephrin levels, and overtly reduced beta-catenin amounts were observed in the HG + NaHS group compared with HG treated cells (P<0.01). Compared with NG treated cells, decreased ZO-2 and nephrin levels and higher beta-catenin amounts were obtained in the HG + NaHS group. In conclusion,CSE downregulation contributes to hyperglycemia induced podocyte injury, which is alleviated by exogenous H2S possibly through ZO-2 upregulation and the subsequent suppression of Wnt/beta-catenin pathway. PMID- 26261568 TI - Expression of the EphA1 protein is associated with Fuhrman nuclear grade in clear cell renal cell carcinomas. AB - Aberrant expression of receptor tyrosine kinase EphA1 in malignant tissues has been reported. However, the expression profile of EphA1 in renal cell carcinoma (RCC) and its association with clinicopathological parameters remain unknown. The aim of this study was to determine the cancerous value of the EphA1 protein expression in patients with renal cell carcinomas. This study included 144 patients with clear cell RCC (ccRCC), 18 patients with chromophobe RCC and 6 patients with papillary RCC. The EphA1 protein was detected in RCC tissue samples by an immunohistochemical staining with a specific polycolonal antibody. The correlation of the expression of the EphA1 protein with clinicopathological parameters was evaluated. High level of the expression of EphA1 was observed in all normal renal tubes. The EphA1 protein was negatively or weakly expressed in 93 out of 144 ccRCC (64.6%) and positively expressed in 51 out of 144 ccRCC (35.4%). The high level expression of the EphA1 protein was significantly associated with younger patients (P<0.001), sex (P=0.016) and lower nuclear grade (P<0.001). No significant relation between the expression of EphA1 and tumor diameter was found (P=0.316). Positive expression of EphA1 was observed in all samples of chromophobe RCC and papillary RCC. Our data indicated that the EphA1 protein may be a new marker for the prognosis of ccRCC. PMID- 26261569 TI - Astragaloside effect on TGF-beta1, SMAD2/3, and alpha-SMA expression in the kidney tissues of diabetic KKAy mice. AB - Numerous cytokines participate in the occurrence and development of inflammation and renal interstitial fibrosis. Previous studies confirmed that TGF-beta1 overexpressed in diabetic nephropathy. As a downstream signal protein of TGF beta1 family, SMAD has an important role in the process of alpha-SMA mediated renal interstitial fibrosis. This study aimed to study astragaloside effect on TGF-beta1, SMAD2/3, and alpha-SMA expression in the kidney tissue of diabetic KKAy mice, to reveal its potential impact on renal interstitial fibrosis. 20 type II diabetic KKAy mice were randomly equally divided into model group and astragaloside group, while 10 male C57BL/6J mice were selected as the control. Astragaloside at 40 mg/(kg*d) was given when the KKAy mice fed with high-fat diet to 14 weeks old. The mice were killed at 24 weeks old and the kidney tissue samples were collected. Pathology morphological changes were observed. TGF-beta1, SMAD2/3, and alpha-SMA expression levels were determined by immunohistochemistry. Compared with control, mice kidney in model group appeared obvious fibrosis and up-regulated blood glucose level, TGF-beta1, SMAD2/3, and alpha-SMA expression (P < 0.05). Mice in astragaloside group exhibited alleviated renal interstitial fibrosis compared with the model. Its blood glucose level, TGF-beta1, SMAD2/3, and alpha-SMA expression levels were significantly lower than the model group (P < 0.05). Astragaloside can delay the renal fibrosis process in diabetic mice by influencing the TGF-beta/SMADS signaling pathway and down-regulating TGF-beta1, SMAD2/3, and alpha-SMA expression. PMID- 26261570 TI - Tenosynovial giant cell tumor arising from the posterior cruciate ligament: a case report and literature review. AB - The localized form of tenosynovial giant cell tumor or pigmented villonodular synovitis is rarely intraarticular in the knee. We reported a 40-year-old woman with a tenosynovial giant cell tumor arising from posterior cruciate ligament (PCL). She suffered sudden knee pain and locking without any reason for two days. A mass with a size of 1.7 * 0.8 * 0.7 cm in the fossa intercondyloidea was detected on the MRI. After one time hyperextension physical examination the patients felt sudden pain relief. During the arthroscopy examination, a loose soft tissue mass was found under the lateral meniscus. Only the synovium tissue lesion on the proximal PCL was detected. The mass had a conceivable thin pedicel and the shape matched well with the tumor bed on the PCL. The histopathology of the mass demonstrated a tenosynovial giant cell tumor. At six weeks follow-up, no clinical evidence of recurrence was noted. A Literature Review of tenosynovial giant cell tumor or pigmented villonodular synovitis arising from the PCL is present. PMID- 26261571 TI - Impact of acute and chronic stress hormone on male albino rat brain. AB - The present investigation aimed to evaluate the acute and chronic effect of stress (stress hormone) in male albino rat brain. Nor-epinephrine was used for the treatment and saline used for the control. Nor-epinephrine was dissolved in the saline and administered orally to the rats. Following nor-epinephrine administration, the brain was removed surgically at 6 h, 12 h and 45 days. Alanine tansaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) were significantly altered in the rats. Lipid peroxidation was measured as malondialdehyde (MDA), showed altered lipid peroxidation. Hematological markers such as packed cell volume (PCV), white blood cells (WBC), neutrophil, lymphocytes and hemoglobin were significantly altered compared to controls. Altered serum biochemical and hematological markers, lipid peroxidation and enzyme activities leads to adverse effect in the cellular metabolism and physiological activities of rats. PMID- 26261572 TI - Analysis of microarray-identified genes and microRNAs associated with drug resistance in ovarian cancer. AB - The aim of this study was to identify potential microRNAs and genes associated with drug resistance in ovarian cancer through web-available microarrays. The drug resistant-related microRNA microarray dataset GS54665 and mRNA dataset GSE33482, GSE28646, and GSE15372 were downloaded from the Gene Expression Omnibus database. Dysregulated microRNAs/genes were screened with GEO2R and were further identified in SKOV3 (SKOV3/DDP) and A2780 (A2780/DDP) cells by real-time quantitative PCR (qRT-PCR), and then their associations with drug resistance was analyzed by comprehensive bioinformatic analyses. Nine microRNAs (microRNA-199a 5p, microRNA-199a-3p, microRNA-199b-3p, microRNA-215, microRNA-335, microRNA-18b, microRNA-363, microRNA-645 and microRNA-141) and 38 genes were identified to be differentially expressed in drug-resistant ovarian cancer cells, with seven genes (NHSL1, EPHA3, USP51, ZSCAN4, EPHA7, SNCA and PI15) exhibited exactly the same expression trends in all three microarrays. Biological process annotation and pathway enrichment analysis of the 9 microRNAs and 38 genes identified several drug resistant-related signaling pathways, and the microRNA-mRNA interaction revealed the existence of a targeted regulatory relationship between the 9 microRNAs and most of the 38 genes. The expression of 9 microRNAs and the 7 genes by qRT-PCR in SKOV3/DDP and A2780/DDP cells indicating a consistent expression profile with the microarrays. Among those, the expression of EPHA7 and PI15 were negatively correlated with that of microRNA-141, and they were also identified as potential targets of this microRNA via microRNA-mRNA interaction. We thus concluded that microRNA-141, EPHA7, and PI15 might jointly participate in the regulation of drug resistance in ovarian cancer and serve as potential targets in targeted therapies. PMID- 26261573 TI - Possible involvement of TGF-beta/periostin in fibrosis of right atrial appendages in patients with atrial fibrillation. AB - Atrial fibrosis contributes to development and recurrence of atrial fibrillation (AF). TGF-beta and periostin have been reported to be involved in fibrogenesis. Here we investigated the role of TGF-beta and periostin in atrial fibrosis of AF and in the recurrence of AF after surgery ablation. Western blot, Masson staining, immunohistochemistry and colorimetry were performed to detect the degree of atrial fibrosis and the expression of TGF-beta, periostin and collagens in 70 biopsies of right atrial appendage (RAA) obtained in this study. Then the patients who received surgical ablation were followed up for about one year. The results showed an increasing gradient of atrial expression of TGF-beta, periostin and collagens paralleled by a higher level of atrial fibrosis in control, SR and AF groups. The expression of TGF-beta and periostin was significantly correlated with fibrotic markers. In addition, LAD and the expression of TGF-beta were larger or higher in recurrence group than that in nonrecurrence group after surgery ablation. The results suggest that upregulated expression of TGF-beta and periostin in RAAs is correlated with the degree of atrial fibrosis in patients with AF. PMID- 26261574 TI - rhEPO affects apoptosis in hippocampus of aging rats by upregulating SIRT1. AB - The aim of this study was to elucidate the signaling pathway involved in the anti aging effect of erythropoietin (EPO) and to clarify whether recombinant human EPO (rhEPO) affects apoptosis in the aging rat hippocampus by upregulating Sirtuin 1 (SIRT1). In this study, a rat model of aging was established using D-galactose. Behavioral changes were monitored by the Morris water maze test. Using immunohistochemistry, we studied the expression of SIRT1, B-cell lymphoma/leukemia-2 gene (Bcl-2), and Bcl-2 associated X protein (Bax) expression, and apoptotic cells in the hippocampus of a rat model of aging in which rhEPO was intraperitoneally injected. The escape latency in rats from the EPO group shortened significantly; however, the number of platform passes increased significantly from that in the D-gal group (P < 0.05). Compared to the D-gal group, in the EPO group, the number of SIRT1 and Bcl-2-positive cells increased (P < 0.05), but the number of Bax-positive cells and apoptotic cells decreased in the hippocampus of aging rats (P < 0.05). These results suggest that rhEPO regulates apoptosis-related genes and affects apoptosis in the hippocampus of aging rats by upregulating SIRT. This may be one of the important pathways underlying the anti-aging property of EPO. PMID- 26261575 TI - The status of perineural invasion predicts the outcomes of postoperative radiotherapy in locally advanced esophageal squamous cell carcinoma. AB - BACKGROUND: Prognosis of locally advanced esophageal squamous cell carcinoma (ESCC) remains dismal even after curative resection and adjuvant radiotherapy. New biomarkers for predicting prognosis and treatment outcomes are needed for improved treatment stratification of patients with locally advanced ESCC. The prognostic and treatment predictive significance of perineural invasion (PNI) in the locally advanced ESCC remains unclear. This study aimed to examine the effect of PNI on the outcomes of locally advanced ESCC patients after curative resection with or without postoperative radiotherapy (PORT). PATIENTS AND METHODS: We retrospectively reviewed 262 consecutive locally advanced ESCC patients who underwent curative resection. Tumors sections were re-evaluated for PNI by an independent pathologist blinded to the patients' outcomes. Overall survival (OS) and disease-free survival (DFS) were determined using the Kaplan-Meier method; univariate log-rank test and multivariate Cox proportional hazard model were used to evaluate the prognostic value of PNI. RESULTS: Finally, 243 patients were analyzed and enrolled into this study, of which 132 received PORT. PNI was identified in 22.2% (54/243) of the pathologic sections. The 5-year DFS was favorable for PNI-negative patients versus PNI-positive patients (21.3% vs. 36.7%, respectively; P = 0.005). The 5-year OS was 40.3% for PNI-negative patients versus 21.7% for PNI-positive patients (P < 0.001). On multivariate analysis, PNI was an independent prognostic factor. In a subset analysis for patients received PORT, PNI was evaluated as a prognostic predictor as well (P < 0.05). In contrast to patients without PORT, PORT couldn't improve the disease recurrence and survival in locally advanced ESCC patients with PNI-positive (P > 0.05). CONCLUSIONS: PNI could serve as an independent prognostic factor and prognosticate treatment outcomes in locally advanced ESCC patients. The PNI status should be considered when stratifying high-risk locally advanced ESCC patients for adjuvant radiotherapy. Future prospective study is warranted to confirm our results. PMID- 26261576 TI - Conserved hypothetical protein Rv1977 in Mycobacterium tuberculosis strains contains sequence polymorphisms and might be involved in ongoing immune evasion. AB - Host immune pressure and associated parasite immune evasion are key features of host-pathogen co-evolution. A previous study showed that human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved and thus it was deduced that M. tuberculosis lacks antigenic variation and immune evasion. Here, we selected 151 clinical Mycobacterium tuberculosis isolates from China, amplified gene encoding Rv1977 and compared the sequences. The results showed that Rv1977, a conserved hypothetical protein, is not conserved in M. tuberculosis strains and there are polymorphisms existed in the protein. Some mutations, especially one frameshift mutation, occurred in the antigen Rv1977, which is uncommon in M.tb strains and may lead to the protein function altering. Mutations and deletion in the gene all affect one of three T cell epitopes and the changed T cell epitope contained more than one variable position, which may suggest ongoing immune evasion. PMID- 26261577 TI - Aldosterone-to-renin ratio acts as the predictor distinguishing the primary aldosteronism from chronic kidney disease. AB - Aldosterone-to-renin ratio (ARR) is a screening test for primary aldosteronism, but it was impacted by a bunch of clinical covariates. The ARR is associated with chronic kidney disease (CKD), renal artery stenosis, renin adenoma. This study aims to investigate relationship between ARR and primary aldosteronism in CKD patients. A retrospective observational analysis involves 253 attendees from Urology Department of Chengdu Military General Hospital (China), comprising 146 patients with confirmed primary aldosteronism, 56 patients with essential hypertension, and 55 patients with chronic kidney disease accounting for primary kidney disease. Blood samples were drawn from patients with particular restriction for measuring serum aldosteronism, plasma renin activity, and serum potassium. Receiver operating characteristic (ROC) curve of ARR was tested to establish cutoff values and to assess sensitivity and specificity. The results showed that LogARR values were significantly higher (P < 0.001), and PRA and serum potassium values were significantly lower (P < 0.001) in primary aldosteronism patients. By contrast, significantly higher serum aldosterone and plasma renin were observed in CKDs compared with the other two groups (P < 0.001). There was a significantly positive correlation between LogARR and serum potassium (r = -0.0345, P < 0.001, R(2) = 0.093). The AUC for plasma renin activity, logARR, and serum aldosterone are 0.855, 0.84, and 0.501, respectively. ROC curve of logARR and plasma renin activity in detection of primary aldosteronism with higher sensitivity and specificity. In conclusion, this study indicated that the ARR act as the biomarker for the primary aldosteronism, and could distinguish from chronic kidney disease. PMID- 26261578 TI - 15-PGDH expression as a predictive factor response to neoadjuvant chemotherapy in advanced gastric cancer. AB - Given the various clinical and pathologic responses to neoadjuvant chemotherapy (NACT) in gastric cancer (GC), potential biomarkers that reflecting the efficacy of NACT on GC should be investigated. The aim of this study was to investigate the 15-PGDH expression response to NACT in GC patients and its relationship with prognosis of GC. Immunohistochemical method was used to assess the level of 15 PGDH expression in 56 GC patients who received NACT before surgery and 46 patients who underwent surgical treatment without NACT as well as their corresponding adjacent non-neoplastic tissues. We found that there was no correlation of 15-PGDH expression between non-cancerous gastric tissues and GC tissues (P=0.519), while 15-PGDH expression level in NACT group was higher than that in nNACT group (P=0.015). In patients with NACT, the higher level of 15-PGDH expression was significantly associated with well-moderately differentiated grade (P=0.023), I/II stage (P=0.014) and with no lymph node metastasis (P=0.016). Moreover, statistically significant differences in overall survival (OS) were found among 15-PGDH expression (log-rank test, P<0.001) and TNM stage (log-rank test, P=0.032). Most importantly, expression of 15-PGDH was found to be an independent predictive factor by multivariate analysis (Hazard ratio (HR) 0.315 [0.120-0.827], P=0.019). These findings indicated that NACT could increase 15 PGDH expression in advanced GC patients, and 15-PGDH may serve as a candidate prognostic biomarker of advanced GC response to NACT. PMID- 26261580 TI - Spatial and temporal differences of HMGB1 expression in the pancreas of rats with acute pancreatitis. AB - We aimed to investigate the spatial and temporal differences in expression between HMGB1 and early-stage inflammatory cytokines (IL-1, IL-6 and TNF-alpha) in pancreas tissue in rats with acute pancreatitis. SD rats (BW 350 +/- 30 g, n = 48) were randomly divided into the experimental group (n = 36) which were injected with 5% sodium taurocholate into the bilipancreatic duct retrogradely to produce acute necrotic pancreatitis (ANP) rat models, and the sham-operated (SO) group (n = 12) injected with equal dose of saline. The rats were sacrificed at different time points at 0 h, 3 h, 6 h, 12 h, and 24 h post modeling, respectively. The peripheral blood amylase and different inflammatory factors in ANP rats at different time points were detected by ELISA, and the expression of HMGB1 in the pancreatic tissue was detected by immunohistochemistry, Western blot and Q-PCR methods. Results showed that the serum amylase in the ANP model rats was significantly higher than the sham-operated group (P < 0.05). The early inflammatory factors (IL-1, TNF-alpha and IL-6) increased quickly at 3 h after the model induction, reached the peak level at 6 h (higher than SO group, P < 0.05), then decreased at 12 h, and at 24 h the levels were lower than those at 12 h (P < 0.05). The HMGB1 level in the pancreatitis tissue did not change significantly at 3 h and 6 h (P > 0.05), however, it increased remarkably at 12 h, and maintained up to 24 h (P > 0.05). As a late inflammatory factor, the expression of HMGB1 in acute pancreatitis was obviously later than the early inflammatory factors IL-1, TNF-alpha and IL-6. HMGB1 may play a key role in maintaining the development of the acute pancreatitis. PMID- 26261579 TI - Overexpression of homeobox B-13 correlates with angiogenesis, aberrant expression of EMT markers, aggressive characteristics and poor prognosis in pancreatic carcinoma. AB - To investigate the expression of homeobox B (Hoxb)-13 and analyze its relationship with tumor angiogenesis, epithelial-mesenchymal transition (EMT) associated markers (E-cadherin and vimentin), clinicopathologic data and prognosis in pancreatic carcinoma. Immunohistochemistry was applied to determine the level of Hoxb-13 expression in tumor tissues and surrounding non-tumor tissues from 85 subjects with pancreatic carcinoma. Besides, vascular endothelial growth factor (VEGF), CD31, E-cadherin and vimentin were also detected in tumor tissues by immunostaining. We found that the level of Hoxb-13 expression was significantly higher in pancreatic carcinoma tissues than in paracarcinomatous tissues (P < 0.05). Hoxb-13 staining was positively correlated with VEGF (r = 0.429, P < 0.001) and microvessel density (MVD) (r = 0.454, P < 0.001). Likewise, Hoxb-13 staining was positively correlated with vimentin (r = 0.448, P < 0.001); while it was negatively correlated with E-cadherin (r = -0.405, P < 0.001). High Hoxb-13 expression was associated with aggressive clinicopathological characteristics, worse disease-free survival (DFS) (P < 0.001) and worse overall survival (OS) (P < 0.001). Multivariate analysis showed that Hoxb-13 was an independent predictor for poor DFS (P < 0.001) and OS (P = 0.002). In conclusion, our data show that overexpressed Hoxb-13 is correlated with tumor angiogenesis, aberrant expression of EMT-associated markers and aggressive clinicopathological characteristics, and serves as a promising marker for unfavourable prognosis in pancreatic carcinoma. PMID- 26261581 TI - Sp1 is over-expressed in nasopharyngeal cancer and is a poor prognostic indicator for patients receiving radiotherapy. AB - Nasopharyngeal cancer (NPC) is a tumor of epithelial origin with complex etiology. Currently the standard treatment of NPC is radiotherapy, but therapy failure is quite common, making radioresistance an important issue. This study explores the association of specificity protein 1 (Sp1) protein expression with clinicopathological significance and disease prognosis in NPC patients receiving radiotherapy. A total of 82 NPC patients (55 males and 27 females, median age: 48 years old) were enrolled and received radiotherapy between September 2011 and March 2014. Tumor tissue and grossly adjacent normal mucosa were obtained in each patient. Sp1 expression was detected by western blot and immunohistochemical analysis, and the associations with clinicopathological status and radiotherapy response were analyzed. Our Results showed Sp1 protein expression was higher in CNE-1 and CNE-2 nasopharyngeal cancer cells than in normal nasopharyngeal mucosal NP69 cells. All 82 patients' tissue sections were stained positive for the Sp1 protein, and 39 (47.6%) patients showed higher level than adjacent normal mucosa. Sp1-overexpression in the tumor tissue was correlated with a higher tumor stage, nodal status, clinical stage and distant metastasis (P < 0.01). Patients with higher Sp1 expression in pretreatment biopsies had a lower radiotherapy response compared to those with lower expression. In conclusion, Sp1 may play roles in radioresistance of nasopharyngeal cancer which attributes to tumor invasiveness, and serve as a novel prognostic marker of NPC radiotherapy. However, further studies are required to validate our findings in larger samples and explore more detailed mechanisms underlying radioresistance of Sp1. PMID- 26261583 TI - PinX1 is up-regulated and associated with poor patients' survival in gliomas. AB - PinX1, a conserved nuclear protein, could maintain telomere integrity and plays an important role in regulating telomerase activity. It has been reported that the expression of PinX1 is down-regulated in some cancer and associated with cancer prognosis. However, the value of PinX1 in gliomas has not been studied. In this study, two independent retrospective gliomas cohorts with the corresponding gliomas tissue microarrays (TMAs) were established to detect the expression level of PinX1 and the correlation of PinX1 expression with the clinicopathological features and the patients' survival. Compared with non-cancerous brain tissues, PinX1 protein levels were remarkably up-regulated in gliomas (P = 0.001), and further increased from benign gliomas tissues to malignant gliomas tissues (P = 0.090). Moreover, high PinX1 expression was significantly positively associated with gliomas WHO grade in the training set (P = 0.019) and the validation set (P = 0.037). High PinX1 expression significantly correlated with a worse 5-year overall (P = 0.016) and disease-specific survival (P = 0.026). Simultaneously, the multivariate COX regression analysis showed that PinX1 was an independent unfavorable prognostic factor for 5-year overall survival (hazard ratio (HR) = 2.078, P = 0.015) and disease-specific survival (HR = 2.429, P = 0.012) after adjusting with age, sex and WHO grade in gliomas. In conclusion, PinX1 expression may serve as a prognostic and predictive biomarker for gliomas. PMID- 26261582 TI - Role of DJ-1 siRNA in reverse sensitivity of breast cancer cells to chemotherapy and its possible mechanism. AB - Breast cancer which has a high incidence rate is the 2(nd) lethal diseases only followed by lung cancer in women. How to improve the recovery rate is the principal problem should be solved in clinical. Previous studies demonstrated the importance of DJ-1 in the existence of breast cancer for the secreted of protein into serum by breast cancer cells both in vitro and in vivo. So the DJ-1 probably could be selected as the target in breast cancer treatment. Adriamycin resistance breast cancer cells MCF-7 and DJ-1 siRNA plasmid were employed to explore the potential clinical application of DJ-1 in this study. Our results showed that the sensitivity of cancer cells to chemotherapeutics was significantly improved with the transfection of DJ-1 siRNA. Further mechanism studies indicated the role of PI3K/AKT/MTOR pathway in the improvement of apoptosis after treatment with adriamycin in DJ-1 silence group. PMID- 26261584 TI - ER stress related factor ATF6 and caspase-12 trigger apoptosis in neonatal hypoxic-ischemic encephalopathy. AB - The specific and available markers proteins of neonatal hypoxic-ischemic encephalopathy (HIE) injury are correlated with disease severity and the disability in childhood. Exploring the mechanism of HIE is very helpful to the targeted therapeutic approach in clinical. This study aims to explore the cell death-related proteins or biomarkers that plays roles in the HIE injury. In this study, 15 patients were included the 487 autopsies patients performed at the Department of Pathology. The lactate dehydrogenase (LDH) assay was used to detect the cell viability of NGF-differentiated PC12 cell. TUNEL assay was employed to examine the apoptotic cells in embedded slides samples. Three ER stress-related protein, including ATF6, p-Perk and IRE-1 were investigated using Western blot assay for the ER stress examination. The apoptosis associated caspase-12 and CHOP protein were detected by Western blot. The results indicated that LDH activity of living cells during hypoxia was significantly enhanced to 45% and 64% after 8 hours and 24 hours. The TUNEL results showed that plenty of the PC12 cells became the positive staining cells when treated with 0.1% O2 hypoxia. ER stress UPR pathway protein, cleaved ATF6, was increased significantly when treated with 0.1% O2 compared with the cells treated with 20% O2. Furthermore, the caspase 12 activation was triggered when the cells treated with the 0.1% O2. In conclusion, apoptosis is served as an important factor that triggers the HIE brain injury through cleaving the ATF6 and caspase-12 ER stress-related protein. PMID- 26261585 TI - Prognostic value of transformer 2beta expression in prostate cancer. AB - BACKGROUND: Deregulation of transformer 2beta (Tra2beta) has been implicated in several cancers. However, the role of Tra2beta expression in prostate cancer (PCa) is unclear. Therefore, this study was to investigate the expression of Tra2beta in PCa and evaluated its association with clinicopathological variables and prognosis. METHODS: Thirty paired fresh PCa samples were analyzed for Tra2beta expression by Western blot analysis. Immunohistochemistry (IHC) assay was performed in 160 PCa samples after radical prostatectomy and adjacent non cancerous tissues. Tra2beta protein expression was divided into high expression group and low expression group by IHC. We also investigated the association of Tra2beta expression with clinical and pathologic parameters. Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the association between Tra2beta protein expression and prognosis of PCa patients. Our results showed that Tra2beta was significantly upregulated in PCa tissues by western blot and IHC. RESULTS: Our data indicated that high expression of Tra2beta was significantly associated with lymph node metastasis (P=0.002), clinical stage (P=0.015), preoperative prostate-specific antigen (P=0.003), Gleason score (P=0.001), and biochemical recurrence (P=0.021). High Tra2beta expression was a significant predictor of poor biochemical recurrence free survival and overall survival both in univariate and multivariate analysis. CONCLUSION: We show that Tra2beta was significantly upregulated in PCa patients after radical prostatectomy, and multivariate analysis confirmed Tra2beta as an independent prognostic factor. PMID- 26261586 TI - Increased expression of Rab5A predicts metastasis and poor prognosis in colorectal cancer patients. AB - Rab5A is reported to correlate with cancer development and progression. The purpose of this study is to explore the association between Rab5A expression and the clinical characteristics of colorectal cancer (CRC). Data containing three independent investigations from Oncomine database demonstrated that Rab5A is overexpression in CRC compared with normal tissue, similar result was also found in 32 matched CRC tissue samples by qPCR. The protein expression of Rab5A was examined in 390 CRC specimens and the results showed that high expression of Rab5A was significantly correlated with tumor size (P = 0.008), serum CEA (P = 0.002), liver metastasis (P = 0.014) and clinical stage (P = 0.010). Kaplan-Meier method suggested that overexpression of Rab5A protein expression had shorter overall survival times in CRC patients (P < 0.001). Multivariate Cox regression analysis confirmed Rab5A expression, tumor size and clinical stage as independent prognostic factor in CRC. In conclusion, the data indicated that higher expression of Rab5A was observed in CRC tissues and Rab5A may be identified as a useful predictor of metastasis and prognosis for CRC. PMID- 26261587 TI - Anti-hypertensive effect of Lycium barbarum L. with down-regulated expression of renal endothelial lncRNA sONE in a rat model of salt-sensitive hypertension. AB - The present study aims to test whether Lycium barbarum L. has anti-hypertensive effect through regulating expression of lncRNA sONE in a rat model of salt sensitive hypertension. Nine weeks old borderline hypertensive rats (BHRs) were divided into 4 groups receiving high (8% NaCl), medium (0.25% NaCl, as control group), and low salt diet (0.015% NaCl) for 16 weeks, respectively, while the fourth group (high salt + L. barbarum group) fed with high salt diet for 12 weeks, then followed by 8% NaCl and L. barbarum treatment for 4 weeks. Body weight and blood pressure were recorded biweekly. Salt-sensitive hypertension was successfully induced by 12-week high salt diet in BHR model. Blood pressure was significantly increased in the model (P < 0.05), and L. barbarum treatment reversed the elevated blood pressure to normal level. Expression of lncRNA sONE was significantly reduced and eNOS expression level was dramatically improved in the hypertension model rats with the L. barbarum compared with that receiving high salt diet. Our results indicated that L. barbarum L. had anti-hypertensive effect and might lower blood pressure by suppressing the expression of lncRNA sONE in BHR model. PMID- 26261588 TI - Up-regulated miR-155-5p promotes cell proliferation, invasion and metastasis in colorectal carcinoma. AB - BACKGROUND AND OBJECTIVE: Emerging evidences indicate that miR-155-5p is associated with some cancer tumorigenesis, but their specific effects on proliferation, invasion and metastasis of colorectal carcinoma (CRC) are still poorly understood. The aim of the study is to investigate miR-155-5p effect on proliferation and invasion metastasis of CRC. METHODS: Retrospectively analyzed clinicopathological parameters and fresh tissue samples of 372 colon cancer patients receiving radical surgery. HT-29 cells were transfected with mimics and inhibitors of miR-155-5p, respectively. Real-time reverse transcription-PCR was performed to measure miR-155-5p relative levels of tissues and cells. RESULTS: miR-155-5p expression in cancer group was higher than that in normal group, with statistical differences (P<0.05). miR-155-5p expression was associated with tumor location, tumor grade, TNM staging and distant metastasis (P<0.05 for all parameters). Cell number of mimics group was higher than control group (P<0.01), and that of inhibitor group was lower than control group (P<0.05). Invasion and metastasis effect of mimics group were the highest and those of inhibitor group were the lowest. CONCLUSIONS: miR-155-5p expression is up-regulated in most CRC and promotes proliferation, invasion and metastasis of CRC cells. It may play an essential role in tumorigenesis and tumor progression of CRC. PMID- 26261589 TI - Relationship between the expression of MDR1 in hepatocellular cancer and its biological behaviors. AB - OBJECTIVE: By the detection of HBV infection, AFP and AST, the targets of biological behavior and the gene expression of multi-drug resistance gene 1 (MDR1) in hepatocellular carcinoma (HCC), we investigate characteristics of the expression of MDR1 in HCC and its relationship with HCC biological behavior. METHODS: Using real-time fluorescence quantitative PCR (FQ-PCR) to detect the expressions of MDR1 in 102 samples of HCC tissue and 20 samples of non-cancerous tissue, we analyze the relationship between expressions of MDR1 and biological characteristics of HCC. RESULTS: The expression of MDR1 in HCC is 0.55 +/- 0.27, and in normal liver tissues is 0.23 +/- 0.10, respectively. The expression in HCC is higher than it in normal liver tissue, the difference is statistically significant (P<0.05) and the difference between the expression and the HCC envelopes is statistically significant, and the expression increases along with the increase of Edmondson classification (P<0.05). HBV infection, AFP positive, the rise of AST, all these factors have positive correlations with the expression (r=0.463, 0.473, 0.299). In MDR1 expressions of HCC patients, the survival curve of the negative is higher than that of the positive, but the difference is not statistically significant. CONCLUSION: There are drug resistance phenomena in HCC, MDR1 expression may play an important role in primary HCC drug resistance. HBV infection can be detected as a reference indicator of HCC chemotherapy resistance, plasma levels of AFP, AST can be used as a reference index change dynamic monitoring of MDR1 expression. PMID- 26261590 TI - Increased chemokine receptor IL-17RA expression is associated with poor survival in gastric cancer patients. AB - BACKGROUND: Previous researchers have identified that the chemokine interleukin 17 (IL-17) was associated with survival time of patients with gastric cancer, but the roles of its receptors (IL-17R) in gastric cancer remain unknown. Our studies were designed to clarify the function of IL-17RA and to explore their potential role in gastric cancer. MATERIALS AND METHODS: The expression of IL-17RA was determined in primary gastric cancer tissues (n=101) using Real-time RT-PCR, immunohistochemistry, and western blotting. To investigate the functional significance of IL-17RA expression, IL-17RA expression and clinical parameters, multivariate survival was analyzed in patients with gastric cancer. RESULTS: IL 17RA was overexpression in gastric cancer tissues compared with adjacent normal tissues (P<0.05). The elevated expression level of IL-17RA was observed correlated significantly with tumor progression (P=0.003), Lymphatic invasion (P=0.019), lymphoid nodal status (P=0.001), distant metastasis (P<0.001) of gastric cancer patients, TNM stage (P=0.0013) and was one of the independent prognostic factors for patient's overall survival. CONCLUSIONS: These results demonstrated that the expression of IL-17RA plays an important role in gastric cancer progression, migration and prognosis of gastric cancer. The IL-17-IL-17RA signaling mechanism may be a potential novel target. PMID- 26261591 TI - Expression of phospho-mTOR kinase is abundant in colorectal cancer and associated with left-sided tumor localization. AB - PURPOSE: To investigate the significance of mammalian target of rapamycin (mTOR) in colorectal cancers. mTOR has recently been suggested as a prognostic biomarker and therapeutic target in an array of human cancers. FINDINGS: phospho-mTOR (p mTOR) expression was analyzed by immunohistochemistry (IHC) on a tissue microarray containing 1800 colorectal cancers (CRC). Clinical follow-up data were available from all cancer patients. Positive p-mTOR immunostaining was seen in 83.5% of 1640 interpretable CRC and was considered weak in 862 (52.5%) and strong in 508 cases (31.0%). Matching clinico-pathological parameters were available in 1580 cases. p-mTOR staining was more frequent in tubular adenocarcinomas than in the less common histological subtypes (mucinous, medullary, signet cell; P=0.0163) and significantly linked to carcinomas of the left-sided colon and rectum as compared to right-sided CRC (P=0.0066). There was no significant association between p-mTOR expression and patients' gender, tumor stage, tumor grade or nodal status. In a survival analysis, p-mTOR IHC status of all CRC was unrelated to patient survival (P=0.702). In a multivariate analysis including pT, pN, tumor grade, tumor localization and p-mTOR expression, only pT, pN (both P<0.0001) and grade (P=0.0001) showed prognostic impact, but not tumor localization (P=0.9472) or p-mTOR expression (P=0.8879). CONCLUSION: Our observations indicate that p-mTOR overexpression is abundant in CRC and linked to left-sided tumor localization. The high frequency and overexpression of p-mTOR is providing further rationale for targeting this pathway therapeutically in CRC patients. However, a prognostic role of p-mTOR overexpression in CRC could not be confirmed. PMID- 26261592 TI - Decreased expression of miR-378 correlates with tumor invasiveness and poor prognosis of patients with glioma. AB - microRNAs (miRNAs) are a class of small non-coding RNAs that play important roles in a variety of biological process. It has been reported that dysregulation of miRNA is always associated with cancer progression and development, and miR-378 aberrant expression has been found in some types of cancers. However, the association of miR-378 and glioma has not been evaluated. In this work, we measured the expression of miR-378 in glioma tissues and non-neoplastic brain tissues was measured using real-time PCR, and found that miRNA-378 expression level was significantly lower in glioma tissues compared with non-neoplastic brain tissues. Patients with lower miR-378 expression level had significantly poorer overall survival. Multivariate Cox regression analysis showed that miR-378 expression was an independent prognostic factor for 5-year overall survival. Over expression of miR-378 inhibits glioma cell migration and invasion. In conclusion, our results indicated that miR-378 may serve as a tumor suppressor and play an important role in inhibiting tumor migration and invasion. Our work implicates the potential effect of miR-378 on the prognosis of glioma. PMID- 26261593 TI - Mitochondrial genetic analysis in a Chinese family suffering from both mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes and diabetes. AB - To investigate the mitochondrial mutations in patients suffering from both mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) and maternally inherited diabetes. MELAS was confirmed by muscle biopsy performed from the biceps muscle of the proband. Mitochondrial DNA (mtDNA) was isolated from peripheral blood mononuclear cells. The significant mtDNA loci of other 14 family members were further detected according to the sequencing results of the proband. Direct sequencing of PCR products was used to identify the mitochondrial mutations. The proband (III 1) and her brother (III 3) both harbored the tRNALeu (UUR) A3243G mutation, with heteroplasmic levels of 50% and 33% respectively. Moreover, another two mitochondrial variants, A8860G and A15326G, were also detected in the samples of all the family members. MELAS and diabetes can coexist in one patient, and the main cause for these diseases is the tRNALeu (UUR) A3243G mutation. However, other gene variants may contribute to its pathogenesis. This case also supports the concept that both syndromes can be regarded as two phenotypes of the same disease. PMID- 26261594 TI - Expression of exogenetic enhanced green fluorescent protein in rat endocranium through lentivirus infection. AB - The study aims to investigate whether exogenetic green fluorescent protein is able to express in the endocranium of rats, and to establish a method for further study in exogenetic gene knock-in or gene overexpression. Forty female Sprague Dawley (SD) rats were randomly divided into 4 groups with 10 in each: low and high dose groups, treated with 10% and 100% EGFP-lentivirus, respectively; negative control group, treated with virus enhancer; sham group, treated with normal saline. Seven days later, half rats' brain tissues were perfusion fixed and fresh brain tissues were obtained from the rest after euthanasia in each group. Immunohistochemical analysis, Western blotting and RT-PCR were respectively performed to detect the site where EGFP expressed and its levels. Immunohistochemical analysis demonstrated that EGFP was successfully expressed in brain tissue of those rats infected with EGFP-lentivirus. Both Western blotting and RT-PCR showed that EGFP was expressed after treatment with EGFP-lentivirus, and the expression level increased with the dosage of the vector. Exogenetic EGFP gene can express in brain tissue of the rat, which laid a solid foundation for future studies in exogenetic gene knock in or gene overexpression. PMID- 26261595 TI - Significance of TLR4/MyD88 expression in breast cancer. AB - OBJECTIVE: To investigate the expression of TLR4/MyD88 in breast cancer, and explore the relationship between their expression and breast cancer tumor growth and invasion. METHODS: We examined the protein expression of TLR4 and MyD88 in 60 cases of histologically confirmed breast cancer. The relationship of their protein expressions with clinical features including age at diagnosis, tumor size and stage, lymph node metastasis and distant metastasis were analyzed. RESULTS: The IHC results showed that TLR4 and MyD88 were expressed in 63.3% (38/60) and 58.3% (35/60) of malignant breast tumors respectively. TLR4 expression in breast cancer were significantly higher than in fibroadenoma (n = 4, 20.0%) and adjacent normal tissues (n = 2, 10.0%) (P < 0.001). MyD88 expression in breast cancer were also significantly higher than in fibroadenoma (n = 4, 20.0%) and adjacent normal tissue (n = 3, 15.0%) (P < 0.001). The gene expressions of TLR4 and MyD88 were significantly higher in breast cancer than in fibroadenoma and adjacent normal tissues (P < 0.05). The protein expressions of TLR4 and MyD88 were also significantly associated with poor clinical features (P < 0.05). CONCLUSION: TLR4 and MyD88 expression might be associated with breast cancer growth and regional and distant metastases. PMID- 26261596 TI - Effect of shRNA targeted against RhoA on proliferation and migration of human colonic cancer cells. AB - OBJECTIVE: To study the effects of RhoA siRNA on the malignant phenotypes of human colorectal cancer cell line LoVo. METHODS: The siRNA expression vector pGPU6/GFP/Neo-shRNA-RhoA targeting the mRNA of RhoA and vector pGPU6/GFP/Neo-NC (as a control) were constructed, and then transfected into LoVo cells. The expression of Survivin was detected by real-time fluorescent quantitative polymerase chain reaction and Western blot. The malignant phenotypes of transfected LoVo cells, including invasive activities and adhesive capabilities, were analyzed. RESULTS: RhoA mRNA and protein level were decreased after the pshRNA-RhoA transfection. The cell adhesion rates significantly decreased in the cells transfected with pshRNA-RhoA. The migrating number of LoVo cells (26.5 +/- 0.9) transfected with pshRNA-RhoA was also significantly decreased as compared with the control group (53.7 +/- 1.4). CONCLUSIONS: The sequence specific shRNA against RhoA constructed in the study can block the expression of RhoA in LoVo cell effectively and specifically; Blocking the expression of RhoA in LoVo cells transfected with pshRNA-RhoA can reduce their invasive and adhesive capabilities. PMID- 26261597 TI - Primary renal diffuse large B-cell lymphoma with central nervous system involvement: a rare case report and literature review. AB - Primary renal lymphoma is a rare entity. Of these, diffuse large B-cell lymphoma is the most common pathological type and, R-CHOP regimen was the preferred chemotherapy for it. Here we present an adult case of primary renal diffuse large B-cell lymphoma. PMID- 26261598 TI - Integrated analysis of transcription factor, microRNA and LncRNA in an animal model of obliterative bronchiolitis. AB - Obliterative bronchiolitis (OB) is characterized by sub-epithelial inflammatory and fibrotic narrowing of the bronchioles, and it is the predominant factor limiting long-term survival after lung transplantation. To explore molecular mechanism of OB, we investigated the interaction of transcription factor (TF), microRNA, long noncoding RNA (lncRNA), and gene expression in the mice model of OB by integrated analysis of TF array, miRNA microarray, and lncRNA and mRNA microarray. After 28 days of orthotopic tracheal transplantation in mice, 42 TFs were significantly up-regulated in allogeneic graft compared to syngeneic graft; 62 miRNAs including miR-376-5p were up-regulated and 17 miRNAs including miR-338 3p were down-regulated over 2-fold; 137 mRNAs were down-regulated and 129 mRNAs were up-regulated over 2-fold; 234 lncRNAs were up-regulated and 212 lncRNAs were down-regulated over 2-fold in the allogeneic model compared to that in the syngeneic control group. We further analyzed potential interaction between TFs, miRNAs, lncRNAs and target genes by different algorithms. Four differentially expressed TFs (Myc/Max, FOXO1, FOXM1, and SMAD) were predicted to regulate 3 different miRNAs, 17 mRNAs, and 16 lncRNAs. These findings suggest that modulation of altered transcription factors such as Myc/Max and FOXO1, and miRNAs such as miR-376-5p and miR-338-3p may become a preventive or therapeutic targets in the chronic lung allograft dysfunction. PMID- 26261599 TI - Polymorphisms in poly (ADP-ribose) polymerase-1 (PARP1) promoter and 3' untranslated region and their association with PARP1 expression in breast cancer patients. AB - Within the past several years, inhibition of the PARP1 activity has been emerged as one of the most exciting and promising strategies for triple-negative breast cancer (TNBC) therapy. The purpose of this study is to assess PARP1 expression in TNBCs and to evaluate the association between polymorphisms in PARP1 promoter or 3' untranslated region (3'UTR) and PARP1 expression. It was found that PARP1 was overexpressed in nuclear (nPARP1), cytoplasm (cPARP1) and nuclear-cytoplasmic coexisting (coPARP1) of 187 TNBCs in comparison to that of 115 non-TNBCs (nPARP1, p<0.001; cPARP1, p<0.001; coPARP1, p<0.001). High expression of nPARP1 and cPARP1 in breast cancer was related to worse progression-free survival (nPARP1, p=0.007, cPARP1, p=0.003). Additionally, we identified seven published polymorphism sites in the promoter region and in 3'UTR of PARP1 by sequencing. rs7527192 and rs2077197 genotypes were found to be significantly associated with the cPARP1 expression in TNBC patients (rs7527192 AA+GA versus GG, p=0.014; rs2077197 AA+GA versus GG, p=0.041). These findings were confirmed in an independent validation set of 88 TNBCs (rs7527192 GG versus GA+AA, p=0.030; rs2077197 GG versus GA+AA, p=0.030). The PARP1 over-expression including nuclear, cytoplasm and nuclear cytoplasmic coexisting is a feature of TNBCs and the assessment of its expression may help to predict the efficacy of chemotherapy with PARP1 inhibitor. PMID- 26261600 TI - SATB2 is a sensitive marker for lower gastrointestinal well-differentiated neuroendocrine tumors. AB - Special AT-rich sequence binding protein-2 (SATB2) is selectively expressed in the lower gastrointestinal tract mucosa and has been identified as a sensitive marker for colorectal adenocarcinomas. The goal of this study was to investigate the expression of SATB2 in well-differentiated neuroendocrine tumors to explore its potential as a diagnostic marker for hindgut well-differentiated neuroendocrine tumors. Immunohistochemical staining with a monoclonal antibody to SATB2 was performed on full tissue blocks in 167 well-differentiated neuroendocrine tumors of various origins. The staining was semi-quantitatively scored as 0 (no tumor cell staining), 1+ (1-25%), 2+ (26-50%), 3+ (51-75%) and 4+ (76-100%). Positive SATB2 staining was seen in 17% foregut (14/84, 12/66 primary and 2/18 metastatic), 12% midgut (3/22, 3/18 primary and 0/7 metastatic), and 90% hindgut (52/58, 44/49 primary and 8/9 metastatic) well differentiated neuroendocrine tumors. Most hindgut well-differentiated neuroendocrine tumors (41/58) showed 4+ staining. The specificity of SATB2 for foregut, midgut and hindgut well-differentiated neuroendocrine tumors was 34%, 54% and 84%, respectively. Our results indicate that SATB2 is a sensitive marker for hindgut well-differentiated neuroendocrine tumors though it is not entirely specific. SATB2 should be included in the immunohistochemical panel in working out metastatic well-differentiated neuroendocrine tumor of an unknown origin. PMID- 26261601 TI - Polymorphisms and phenotypic analysis of cytochrome P450 3A4 in the Uygur population in northwest China. AB - PURPOSE: Genetic polymorphisms in CYP3A4 can change its activity to a certain degree, thus leading to differences among different populations in drug efficacy or adverse drug reactions. METHODS: The study was intended to validate the genetic polymorphisms in CYP3A4 in Uygur Chinese population, we sequenced and screened for genetic variants including 5'UTR, promoters, exons, introns, and 3'UTR region of the whole CYP3A4 gene in 100 unrelated, healthy. RESULTS: Twenty one genetic polymorphisms in CYP3A4, and nine of them were novel. We detected CYP3A4*8, a putative poor-metabolizer allele, with the frequency of 0.5% in Uygur population. Tfsitescan revealed that the density of transcription factor varied in the different promoter regions, among which some were key regions for transcription factor binding. CONCLUSION: our results provide basic information about CPY3A4 alleles in Uygur and suggest that the enzymatic activities of CPY3A4 may differ among the diverse ethnic populations of China. PMID- 26261602 TI - The potential of plasma miRNAs for diagnosis and risk estimation of colorectal cancer. AB - Circulating microRNAs (miRNAs) were recognized to be potential non-invasive biomarkers for colorectal cancer (CRC) detection and prediction. Meanwhile, the association of the expression of plasma miRNAs with the risk of CRC patients has rarely been analyzed. Therefore, we conducted this study to evaluate the value of plasma miRNAs for CRC diagnosis and risk estimation. Fasting blood samples from 100 CRC patients and 79 cancer-free controls were collected. Plasma miR-106a, miR 20a, miR-27b, miR-92a and miR-29a levels were detected by RT-qPCR. Sensitivity and specificity were employed to evaluate the diagnostic value of miRNAs for CRC. Univariate and multivariate logistic regression were employed to analyze the association between miRNAs expression and CRC risk. As results, miR-106a and miR 20a were elevated in the patients with CRC. The sensitivity of miR-106a was 74.00% and the specificity was 44.40%, while the cutoff value was 2.03. As for miR-20a, the sensitivity was 46.00% and specificity was 73.42% when employed 2.44 as cutoff value. High expression of plasma miR-106a increased CRC risk by 1.80 fold. Plasma miR-106a and miR-20a may as noninvasive biomarkers for detecting the CRC. High expression of miR-106a associated with CRC risk. PMID- 26261603 TI - Involvement of bone marrow in lymphoma: pathological investigation in a single center from northern China. AB - OBJECTIVES: This study aimed to evaluate key features of bone marrow trephine biopsy (BMT) involvement of lymphoma in Northern China. METHODS: 950 cases were assessed for the occurrence of bone marrow involvement and architectural features including volume percentage, involvement pattern (diffuse, nodular, focal, para trabecular, or interstitial), and presence/absence of background changes (granuloma, stromal fibrosis or necrosis). Correlations with bone marrow aspirate (BMA) and flow cytometry (FCM) findings were made in a subset of paired cases (359 BMA and 364 FCM). RESULTS: 153 (16.1%) cases involved BMT. The most frequent type was mantle cell lymphoma (28/153, 18.3%). Architectural features were similar to previous studies except that diffuse large B-cell lymphoma (DLBCL) preferred focal pattern (16/22 cases, 72.7%) most of all. BMA and BMT agreed in 84.1% of cases (302 of 359: 277 both negative, 25 both positive), while FCM and BMT agreed in 80.8% of cases (294 of 364: 242 both negative, 52 both positive). Both varied widely among different subgroups. CONCLUSIONS: Occurrence of BMT involvement by lymphoma in Northern China is relatively low. The volume percentage, distribution patterns and background changes may be useful pointers towards a particular lymphoma type in Chinese. FCM is more sensitive and reliable than BMA in China. PMID- 26261604 TI - High expression of COUP-TF II cooperated with negative Smad4 expression predicts poor prognosis in patients with colorectal cancer. AB - OBJECTIVE: In order to evaluate whether the role of chicken ovalbumin upstream promoter transcription factor II (COUP-TF II) could sever as a predictor to stratify risk of human colorectal cancer (CRC) patients, and to elucidate the preliminary molecular mechanisms of COUP-TF II involved in the development and advancement of CRC reflected by investigating the relationship of COUP-TF II with PTEN, Smad4. METHODS: 112 cases tissue microarray and immunohistochemical SP method were used to detect the expression of COUP-TF II, PTEN and Smad4 in CRC tissues and adjacent non-tumorous tissues. The clinical relevance and prognosis of COUP-TF II, PTEN, Smad4 in CRC patients were analyzed. Furthermore, Cox proportional hazards model was performed to indicate the independent prognostic factors for CRC patients using various clinicopathological parameters and COUP-TF II, PTEN and Smad4. RESULTS: COUP-TF II proteins were positively expressed in 65.2% of CRC tissues and 15.5% paired non-CRC tissues, respectively. The expression of COUP-TF II was significantly correlated with TNM stage and lymph node metastasis and a negative correlation with Smad4 expression. Patients bearing higher levels of COUP-TF II expression showed lower DFS and OS. Most importantly, Cox proportional hazards regression analyses showed COUP-TF II positive/Smad4 negative status (DFS, P=0.001; OS, P=0.005) were independent prognostic factors for CRC patients. CONCLUSION: Positive COUP-TF II expression levels has significant value in determining CRC stage and metastasis and cooperates with negative Smad4 expression contributing to assess prognosis in patients with colorectal cancer, suggesting Smad4 may be involved in the above regulation progress probably. PMID- 26261605 TI - Expression of Wnt11 and Rock2 protein with clinical characteristics of esophageal squamous cell carcinoma in Kazakh and Han patients. AB - BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most malignancies with a very poor outcome in China. Wnt11 and Rock2, new identified proteins highly associated with metastasis of many cancers, which were never reported in esophageal squamous cell carcinoma (ESCC). Here we measured the expression levels of Wnt11 and Rock2 in tissues from 265 patients with ESCC. Immunohistochemical staining was employed to detect the correlation of Wnt11 and Rock2 expression with clinicopathological features. METHODS: The expression of Wnt11 and Rock2 was detected by immunohistochemistry in esophageal squamous cell carcinomas and normal esophageal tissues. A chi-square test was used to assess the statistical significance of the correlations between Wnt11, Rock2 expression and different clinicopathological parameters, respectively. RESULTS: The high expression of Wnt11 and Rock2 was observed in ESCCs. Seventy-five cases of ESCC (51.7%) showed a positive expression of Wnt11, which indicated a significant association with the AJCC stage (P=0.007). Ninety-eight cases of ESCC (65.5%) showed a positive expression of Rock2, which indicated a significant association with ethnic background. There were no close correlations between Rock2 expression and gender, tumor location, AJCC stage, lymph node metastasis. Specifically, the expression of Rock2 was significantly different between Hans and Kazaks ethnicities (P=0.000). In Kaplan-Meier curve analysis, no significant correlation was observed between the expression of Wnt11, Rock-2 and the poor prognosis of ESCCs. CONCLUSION: Our finding suggests that the over-expression of Rock2 may play an important role in the carcinogenesis and progression, and may become a new underlying molecular marker in the diagnosis and treatment in ESCC. PMID- 26261606 TI - Dysregulation of miRNA-21 and their potential as biomarkers for the diagnosis of cervical cancer. AB - OBJECTIVE: This study aimed to characterize the miR-21 and evaluated its clinical significance. METHODS: Total RNA was extracted from 30 pairs of fresh specimens of cervical cancer and normal tissues. The expression levels of the miR-21-3p and miR-21-5p were detected by quantitative reverse transcriptase polymerase chain reaction, with U6 as the internal reference gene. We compared the expression of miR-21-3p and miR-21-5p between study group and control groups, the association between miRNA expression level and clinicopathological factors was investigated. RESULTS: The expression of miR-21-3p and miR-21-5p in HPV positive cervical cancer samples was significantly upregulated compared to that in the paired normal samples (P < 0.05); A multivariate analysis demonstrated that the expression of miR-21 was associated with clinicopathological parameters, including depth of invasion and lymph node metastasis. CONCLUSIONS: MiR-21 upregulation is associated with aggressive progression and poor prognosis in cervical cancer, which suggests that miR-21 might be identified as an independent marker for predicting the clinical outcome of cervical cancer patients. PMID- 26261607 TI - Protein-DNA array-based identification of transcription factor activities differentially regulated in obliterative bronchiolitis. AB - Lung transplantation has already become the preferred treatment option for a variety of end-stage pulmonary failure. However the long-term results of lung transplantation are still not compelling and the major death reason is commonly due to obliterative bronchiolitis (OB) which is considered as chronic rejection presenting manifests physiologically as a progressive decline in FEV1. Transcription factors (TFs) play a key role in regulating gene expression and in providing an interconnecting regulatory between related pathway elements. Although the transcription factors are required for expression of the proinflammatory cytokines and immune proteins which are involved in obliterative bronchiolitis following lung transplantation, the alterations of the transcription factors in OB have not yet been revealed. Therefore, to investigate the alteration pattern of the transcription factors in OB, we used protein/DNA arrays. Mice orthotopic tracheal transplantation model was used in this studying. In this study, we explored the activity profiles of TFs in Protein/DNA array data of tracheal tissue in 14 and 28 day after transplanted. From a total of 345 screened TFs, we identified 42 TFs that showed associated with OB progression. Our data indicate that TFs may be potentially involved in the pathogenesis of OB, and can prevent, diagnose and treat OB after lung transplantation. In development of OB, some of the TFs may have ability to modulate the transcription of inflammatory proteins such cytokines, inflammatory enzymes and so on. PMID- 26261608 TI - Altered expression of estrogen receptor beta2 is associated with different biological markers and clinicopathological factors in papillary thyroid cancer. AB - Estrogen and estrogen receptor (ER)-alpha and -beta play a role in the development and progression of thyroid cancer. ERbeta2 is one major splicing variant of ERbeta. In this study, we investigated the clinical significance of ERbeta2 protein expression in the papillary thyroid carcinoma (PTC) lesion. ERbeta2 expression was immunohisto-chemically examined in formalin-fixed, paraffin-embedded thyroid tissues from 106 patients with PTC by ElivisionTM plus two-step system as previously described. The relationships between ERbeta2 expression and clinicopathological/biological factors were then analyzed. ERbeta2 protein was expressed in all the PTC patients studied. It was positively associated with Ki-67 expression in female PTC patients with advanced reproductive age (>45 years, in low-estrogen status) and with VEGF expression in male PTC patients with reproductive age (18~45 years, in low-estrogen status) (P=0.005 and P=0.044, respectively). There was no association between ERbeta2 expression and tumor size, extrathyroidal extension and tumor-node-metastasis stage in PTC patients. In addition, ERbeta2 expression was lower in female patients of reproductive age (18~45 years, in relatively high-estrogen status) with lymph node metastasis than that in those patients without lymph node metastasis (P=0.035). The present results suggest that the expression of ERbeta2 in PTC is associated with the progression of the disease. Its potential effect may vary with different estrogen status. Further study will assess the underlying molecular mechanisms of ERbeta2 in PTC. PMID- 26261609 TI - Galectin-1: a biomarker of surgical stress in murine model of cardiac surgery. AB - Galectin-1 (GAL-1) belongs to the family of beta-galactoside-binding lectins. It regulates cell-cell and cell-matrix interactions, the immune response, apoptosis, cell cycle, RNA splicing and neoplastic transformation. We investigate the effect of heart manipulation secondary to cardiac surgery on the level of GAL-1 in murine heart and plasma. Male C57B6/J mice were used for adopted model of cardiac surgery. Heart samples were processed for immunohistochemical and immunofluorescent labeling, Enzyme linked immunosorbent assay and quantitative RT PCR to identify GAL-1 levels in the heart and plasma during the first 24 hours following cardiac surgery. There is significant increase of GAL-1 in the LV at 30 minutes (P<0.000), 60 minutes (P<0.001), 4 hour (P<0.003), and 24 hour (P<0.003) time points of surgically operated groups compared to non-operated control group, while GAL-1 mRNA levels in any of the surgically operated groups are not significantly different from the non-operated group suggesting extracardiac origin of this raise of GAL-1. There is significant increase of GAL-1 in the plasma at 30 minutes (P<0.000), 60 minutes (P<0.009), 4 hour (P<0.043), and 24 hour (P<0.000) time points of surgically operated groups compared to non-operated control group. In conclusion, GAL-1 is valuable biomarker of surgical stress. PMID- 26261610 TI - Expression of poly(C)-binding protein 1 (PCBP1) in NSCLC as a negative regulator of EMT and its clinical value. AB - Poly (C)-binding Protein 1 (PCBP1) is a 35 kDa protein involved in a number of biological processes. Recently, the research found that PCBP1 might be involved in epithelial-mesenchymal transition (EMT). However, the role of PCBP1 in non small-cell lung cancer (NSCLC) metastasis needs further elucidation. The purpose of this study was to determine whether PCBP1 could serve as a biomarker for stratification and prediction of prognosis in NSCLC as a regulator of EMT formation. In this study, PCBP1 expression was evaluated by Western blot in 8 fresh lung cancer tissues and immunohistochemistry (IHC) on 145 paraffin-embedded slices. PCBP1 was highly expressed in non-metastatic NSCLC specimens and significantly correlated with lymph node status (P < 0.001), clinical stage (P = 0.001), vimentin expression (P = 0.033) and E-cadherin expression (P = 0.042). Our study showed that the low expression of PCBP1 was correlated with decreased expression of E-cadherin and elevated expression of vimentin, which were the markers of EMT. Besides, high expression of PCBP1 was correlated with better prognosis. These findings suggested that PCBP1 might play an important role in preventing the process of EMT in NSCLC, thus be a promising therapeutic target to inhibit NSCLC metastasis. PMID- 26261611 TI - Prognostic correlation between MTA2 expression level and colorectal cancer. AB - OBJECTIVES: Association of MTA2 expression with presence, development, metastasis and prognosis of colorectal cancer (CRC) was investigated. METHODS: 90 CRC related cases with follow-up information were made into tissue microarrays according to the paired principle of cancer tissues and the adjacent tissues. Subsequently, the expression of MAT2 was detected with immunohistochemical analysis and SPSS software was finally utilized to analyze the relationships between experimental data and clinical indicatives. RESULTS: Expression of MTA2 in CRC tissues were notably higher than their adjacent tissues (P < 0.001) and showed significant positive correlation with tumor grade (r(2) > 0, P < 0.01). Moreover, survival analysis indicated that MTA2 expression in cancer tissues, serving as an independent correlation factor, was significantly correlated with poor prognosis (P = 0.004). CONCLUSIONS: MTA2 is a crucial biomarker that is closely related with prognosis of CRC and also a potential molecular target for evaluating the prognosis and treatment of CRC. PMID- 26261613 TI - P-selectin gene polymorphism associates with pulmonary hypertension in congenital heart disease. AB - OBJECTIVE: To investigate the relationship between P-selectin gene polymorphism and congenital heart disease (CHD) with pulmonary hypertension (PAH). METHODS: 58 CHD patients with PAH (PAH-CHD), 43 CHD patients without PAH and 205 healthy subjects were included in this study. The concentration of plasma P-selectin was determined by ELISA kits; the direct sequencing of PCR products was used to analyze the P-selectin genotypes. RESULTS: The concentration of plasma P-selectin was markedly higher in PAH-CHD patients than that in CHD subjects and controls, while no difference was observed between CHD group and control. A significant difference of P-selectin genotype -825T/C polymorphism was observed between patients with PAH-CHD and healthy subjects (P<0.05). Logistic analysis showed that the subjects with haplotypes A-G and G-G had lower risk of PAH-CHD compared with the ones with haplotype A-A (OR=0.47, 95% CI=0.24-0.92). In the subjects of PAH-CHD and control, plasma P-selectin concentration was higher in subjects with 825TT genotype than the ones with haplotypes T-C and C-C (P<0.05). CONCLUSION: P selectin probably involves in the development of PAH-CHD. The polymorphism of 825T/C is associated with the risk of PAH-CHD, and may be one of its risk factors. PMID- 26261612 TI - Effect of glycated hemoglobin on heart function of the patients with revascularization of coronary artery. AB - BACKGROUND: Patients with diabetes after coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) treatment for coronary artery disease (CAD) had higher mortality rates than those without diabetes. There were limited data comparing the cardiac and metabolic differences between diabetes and non diabetes for CABG and PCI and about impact of pre-procedure GHb level on systolic heart function in patients with diabetes. AIMS: To explore the cardio-metabolic differences and to evaluate their potential as significant risk factors. SUBJECTS AND METHOD: 124 patients with diabetes and 170 patients without diabetes were enrolled. Coronary lesions (>= 70% stenosis in at least one major coronary artery) were documented by angiography. Patients with diabetes were divided into different groups by GHb, Coronary lesions (>= 70% stenosis in at least one major coronary artery) were documented by angiography. CABG and PCI were performed for all the patients. Cardio-metabolic risk factors before revascularization were compared between them. RESULTS: Diabetics with GHb >= 8% had lower cardiac ejection fraction (EF) values than those with GHb<8% (P<0.05) or patients without diabetes (P<0.05). And count of vascular lesions between the groups was not statistically significant. Observed EF as a dependent variable negatively correlated to GHb levels (P<0.05). The levels of glycated hemoglobin A1c (GHbA1c) rose with increased fasted blood glucose (FBG) values (P<0.001). Even with treatment for hyperglycemia and dyslipidemia, overall levels of fasting blood sugar (FBG, P<0.001), GHbA1c (P<0.001), and triglycerides (TG, P<0.05) in patients with diabetes were still higher than those without diabetes respectively. CONCLUSION: Poorer glucose control with GHb >= 8% and decreased systolic heart function are significant risk factors that potentially contribute to worse prognosis for CABG or PCI treatment. Elevated levels of FBG, GHbA1c, and TG are evident for patients with diabetes compared to patients without diabetes prior to revascularization. PMID- 26261614 TI - Diagnostic value of progesterone receptor, p16, p53 and pHH3 expression in uterine atypical leiomyoma. AB - The differential diagnosis between atypical leiomyoma and leiomyosarcoma may be hard based on morphological criterion at times. It would be helpful to find out biomarkers that can be used to distinguish them. The aim of the study was to investigate the diagnostic value of progesterone receptor (PR), p16, p53 and pHH3 expression in a series of uterine smooth muscle tumors. Immunohistochemical expression of PR, p16, p53 and pHH3 was investigated on 32 atypical leiomyomas, 15 leiomyosarcomas and 15 usual leomyomas. The difference in expression was compared between atypical leiomyoma and other groups. The expression of PR, p16, and pHH3 was found significantly different between atypical leiomyomas and leiomyosarcomas, but lack of significant difference between atypical leiomyomas and usual leiomyomas. There was no significant difference with regard to p53 distribution among these uterine smooth muscle tumors. High p16, pHH3 expression and low PR expression preferred the diagnosis of leiomyosarcoma. The panel of antibodies used in this study is a useful complementary analysis in the assessment of problematic uterine smooth muscle tumors. PMID- 26261615 TI - Squamous differentiation and prognosis in upper urinary tract urothelial carcinoma. AB - Squamous differentiation is the most common histological variation in urothelial carcinoma (UC). However, the clinical significance of squamous differentiation in upper urinary tract UC is unclear. To investigate the significance of squamous differentiation, hematoxylin and eosin stained slides from 140 patients with upper urinary tract UC who underwent nephroureterectomy were reviewed by a single pathologist and the presence of squamous differentiation was recorded. Squamous differentiation was observed in 23 out of 140 studied cases (16%). Squamous differentiation significantly correlated with several adverse prognostic factors including histological grade 3 tumors, presence of lymphovascular invasion, concomitant carcinoma in situ, advanced tumor stage, and occurrence of lymph node metastasis. The Kaplan-Meier and univariate Cox regression analyses revealed that the presence of squamous differentiation was significantly associated with shorter metastasis-free survival [log-rank P = 0.030; univariate hazard ratio (HR), 2.30; 95% confidence interval (CI), 1.06-4.99], cancer-specific survival (log-rank P = 0.0024; univariate HR 3.34; 95% CI, 1.47-7.85), and overall survival (log-rank P = 0.018; univariate HR 2.39; 95% CI, 1.13-5.06) after nephroureterectomy. However, in multivariate analyses, squamous differentiation was not significantly associated with patient outcomes. These findings suggest that squamous differentiation is associated with disease progression, but is not an independent predictor of a worse prognosis in patients with upper urinary tract UC. PMID- 26261616 TI - In vivo and in vitro characteristic of HIF-1alpha and relative genes in ischemic femoral head necrosis. AB - BACKGROUND: Legg-Calve-Perthes Disease (Perthes' disease) is a childhood hip disorder initiated by ischemic necrosis of the growing femoral head. So far, the etiology and pathogenesis of Perthes' disease is poorly understood. MATERIALS AND METHODS: Avascular osteonecrosis rat model was established to mimic the pathophysiological changes of femoral head necrosis. The chondrocytes of newborn Sprague-Dawley rats were isolated and cultured in hypoxic and normoxic condition. The expression characteristic of the hypoxia-inducible factor-1 alpha (HIF 1alpha) was evaluated both in vivo and in vitro models. Vascular endothelial growth factor (VEGF) and apoptotic genes in chondrocytes treated with normoxia and hypoxia were also studied. RESULTS: HIF-1alpha expression increased greatly after ischemic operation and kept at relative high level in the arthromeningitis stage and declined in the stages of osteonecrosis and reconstruction. The HIF 1alpha mRNA levels of chondrocytes incubated at hypoxia were significantly higher than the cells treated with normoxia at 24 and 72 hours. Hypoxia inhibited VEGF expression; chondrocytes could oppose this inhibition manifested by the increasing of VEGF mRNA level after 72 hours hypoxia. The expression of apoptotic genes, Casp3, Casp8 and Casp9, elevated in chondrocytes after hypoxia with time differences. CONCLUSION: Hypoxia might be an etiological factor for femoral head necrosis, HIF-1alpha, VEGF as well as apoptotic genes participated the pathophysiological process of ischemic osteonecrosis. PMID- 26261617 TI - Diethylstilbestrol affects the expression of GPER in the gubernaculum testis. AB - Recent evidence suggested a positive correlation between environmental estrogens (EEs) and high incidence of abnormalities in male urogenital system. EEs are known to cause the abnormalities of testes development and testicular descent. Diethylstilbestrol (DES) is a nonsteroidal synthetic estrogen that disrupts the morphology and proliferation of gubernacular cells, and its nongenomic effects on gubernaculum testis cells may be mediated by G protein-coupled estrogen receptor (GPER). In this study, we detected the expression of GPER in mouse gubernacular testis and investigated the effects of DES on the expression of GPER in gubernaculum testis cells. RT-PCR analysis revealed that GPER mRNA was expressed in the gubernaculum. GPER protein was detected in the parenchymal cells of the gubernaculum early in development. Furthermore, we demonstrate that GPER inhibitor G15 relieved DES-induced inhibition of GPER expression in gubernaculum testis cell, but ER inhibitor ICI 182780 had the converse effects on DES-induced inhibition of GPER expression in these cells. These data suggest that the effects of DES on mouse gubernaculum testis cells are mediated at least partially by the regulation of GPER expression. PMID- 26261618 TI - HOTAIR is upregulated in acute myeloid leukemia and that indicates a poor prognosis. AB - Hox transcript antisense intergenic RNA (HOTAIR) is a long non-coding RNA, its overexpression has been documented in various human solid tumor and it can be considered as a potential cancer biomarker. However, little is known about the role of HOTAIR in acute myeloid leukemia (AML). In this study, We evaluated HOTAIR expression in bone marrow of de novo AML patients, AML-CR patients and normal controls by real-time quantitative reverse transcription-PCR (qRT-PCR), then we inhibited hotair expression of two cell lines by siRNA and evaluated their proliferation by CCK, finally we analyzed its relationship with the clinicopathological parameters of AML. We found that HOTAIR is significantly upregulated in de novo AML patients compared with those of AML-CR patients and normal controls; the reduction of HOTAIR by small interfering RNA (siRNA) repressed the proliferation of HL-60 and K562; the higher expression level of HOTAIR in AML patients was significantly correlated with NCCN high risk group. In conclusion, our study indicated that hotair is highly expressed in AML patients, and hotair expression significantly correlates with clinicopathological prognostic stratification in AML. PMID- 26261619 TI - Intra-thyroid thyroglossal duct cyst: a case report and review of literature. AB - Thyroglossal duct cyst is the most common congenital cyst in the head and neck, which is defined usually occurring in children. However, intra-thyroid thyroglossal duct cyst in an adult is unusually found. Here we describe a case of a 45-year-old woman who was found neck mass along the midline for 5 years. During the surgery we found a separated nodule in the left inferior pole of the thyroid. Surprisingly the diagnosis of the nodule was confirmed by pathology and histological examination demonstrating that it was the thyroglossal duct cyst. Intra-thyroid thyroglossal duct cyst in an adult is a rare finding, with few cases reported. For it is generally thought that any thyroid tissue found in the lateral aspect of the neck may indicate metastatic deposits from well differentiated thyroid carcinoma. Although pathogenesis of an alone thyroglossal duct cyst in the left inferior pole of the thyroid remains unknown, our case could suggest thyroglossal duct cyst should not be excluded in the differential diagnosis of lateral neck masses especially when it simulates nodules in the thyroid. PMID- 26261620 TI - Increased expression of miR-21 predicts poor prognosis in patients with hepatocellular carcinoma. AB - BACKGROUND: MicroRNAs (miRNAs) play critical roles in hepatocellular carcinoma (HCC) development and progression. Aberrant miR-21 expression has been reported in several cancers. However, the clinical significance of miR-21 in human HCC is still unclear. METHODS: A total of 112 patients with primary HCC who underwent a curative liver resection were included in this retrospective study. The differentially expressed amount of the miR-21 was validated by quantitative real time PCR (qRT-PCR). Survival rate was analyzed by log-rank test, and survival curves were plotted according to Kaplan-Meier. Multivariate analysis of the prognostic factors was performed with Cox regression model. RESULTS: As revealed by qRT-PCR analysis, miR-21 expression was significantly upregulated in HCC tissues when compared with adjacent non-tumor tissues (P<0.05). High miR-21 expression level was observed to be closely correlated with tumor differentiation, TNM stage and vein invasion (P<0.05). Patients who had high miR 21 expression had a shorter overall survival than patients who had low miR-21 expression (P<0.05). Moreover, multivariate analysis of the prognosis factors with a Cox proportional hazards model showed that high miR-21 expression was a significant independent predictor of poor survival in HCC (P<0.05). CONCLUSION: Our results suggested that increased expression of miR-21 was significantly correlated with tumor progression and could be a novel potential biomarker for HCC prognosis. PMID- 26261621 TI - Combined evaluation of adenosine deaminase level and histopathological findings from pleural biopsy with Cope's needle for the diagnosis of tuberculous pleurisy. AB - INTRODUCTION: Closed needle pleural biopsy (CNPB) has historically been the gold standard procedure for the diagnosis of pleural tuberculosis. Adenosine deaminase (ADA) is an efficient biomarker for tuberculosis that is measurable in pleural fluids. OBJECTIVE: We compared the diagnostic accuracy of the pleural ADA (P-ADA) level and histopathological findings of CNPB specimens in patients with pleural tuberculosis. METHODS: This prospective study consisted of two groups of examinations with a proven diagnosis of pleural effusion. The P-ADA level was measured in 218 patients with pleural effusion due to a number of causes, and 157 CNPB specimens underwent histopathological analysis. RESULTS: CNPBs were performed in patients with tuberculosis (n=122) and other diseases: adenocarcinoma (n=23), lymphoma (n=5), systemic lupus erythematosus (n=4), squamous cell carcinoma (n=2), and small cell lung cancer (n=1). According to the ROC curve, the optimal cut-off value of the P-ADA level (Giusti and Galanti colorimetric method) was equal to or greater than 40.0 U/L. The diagnostic accuracy of the P-ADA test was 83.0%, and that of histopathological examination of the CNPB tissue, was 78.8% (AUC=0.293, P=0.7695). The association between the P-ADA assay and pleural histopathology was 24.41 (P<0.0001). The tetrachoric correlation coefficient was 0.563 (high correlation). CONCLUSION: In Brazil and other countries with a high incidence of tuberculosis, P-ADA activity is an accurate test for the diagnosis of tuberculous pleural effusions, and its use should be encouraged. The high diagnostic performance of the P-ADA test could to aid the diagnosis of pleural tuberculosis and render CNPB unnecessary. PMID- 26261622 TI - Effect of curcumin on permeability of coronary artery and expression of related proteins in rat coronary atherosclerosis heart disease model. AB - OBJECTIVE: Our objective is to explore the effect of curcumin on permeability of coronary artery and expression of related proteins in rat coronary atherosclerosis heart disease model. METHODS: 45 healthy male Wistar rats of clean grade were selected and divided into treatment group, model control group and blank control group. The rats in the treatment group and model control group received high-fat diet for 12 weeks and intraperitoneal injection of VD3 to establish rat coronary atherosclerosis heart disease model. After modeling, the rats in the treatment group received gavage of 100 mg/(kg.d) curcimin, and the rats in the model control group and blank control group received gavage of 5 ml/(kg.d) distilled water, the intervention time was 4 weeks. After intervention, the rats were killed, and the hearts were dissected to obtain the samples of coronary artery. After embedding and frozen section, immunofluorescence method was used to detect the change of endarterium permeability in 3 groups, Western blot was used to detect matrix metalloproteinase-9 (MMP-9) and CD40L in coronary artery tissue, and enzyme linked immunosorbent assay (ELISA) was used to detect serum tumor necrosis factor-alpha (TNF-alpha) and C reaction protein (CRP). RESULTS: After modeling, compared with the blank control group, total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterin (LDL-c) in the treatment group and model control group were significantly higher (P<0.05), however, high density lipoprotein cholesterin (HDL-c) was significantly lower. The pathological sections showed that there was lipidosis in rat coronary artery in treatment group and model control group, indicating that the modeling was successful. Immunofluorescence showed that there was only a little fluorochrome permeability in artery in blank control group, there was some fluorochrome permeability in artery in the treatment group and there was a lot of fluorochrome permeability in artery in the model control group. MMP-9 and CD40L in coronary artery tissue in the model control group were significantly higher than the treatment group (P<0.05), MMP-9 and CD40L in coronary artery tissue in the treatment group were significantly higher than the blank control group (P<0.05); serum TNF-alpha and CRP in the model control group were significantly higher than the treatment group (P<0.05), which were significantly higher in the treatment group than the blank control group (P<0.05). CONCLUSION: Rat coronary atherosclerosis heart disease model can be successfully established by feeding with high-fat diet and intraperitoneal injection of VD3, the permeability of coronary artery in coronary heart disease rat model is significantly increased, which may be related to up-regulation of MMP-9, CD40L, TNF-alpha and CRP expression. Application of curcumin can inhibit expression of MMP-9, CD40L, TNF alpha and CRP to improve the permeability of coronary artery. PMID- 26261623 TI - Coexisting epithelioid trophoblastic tumor and placental site trophoblastic tumor of the uterus following a term pregnancy: report of a case and review of literature. AB - Gestational trophoblastic neoplasms are a group of fetal trophoblastic tumors including choriocarcinomas, epithelioid trophoblastic tumors (ETTs), and placental site trophoblastic tumors (PSTTs). Mixed gestational trophoblastic neoplasms are extremely rare. The existence of mixed gestational trophoblastic neoplasms that were composed of choriocarcinoma and/or PSTT and/or ETT was also reported. Herein, we present a case of uterine mixed gestational trophoblastic neoplasm which is ETT admixed with PSTT, and reviewed 9 cases of mixed gestational trophoblastic neoplasms reported in English literature available. The most common combination was a choriocarcinoma admixed with an ETT and/or PSTT. Mixed gestational trophoblastic neoplasms present in women of reproductive age and rare in postmenopausal, Abnormal vaginal bleeding is the most common presenting symptom, serum beta-HCG levels are elevated, mostly below 2500 mIU/ml, the tumor was limited to uterus in 7 cases, the rest of 3 with pulmonary metastases at the time of diagnosis. Mixed gestational trophoblastic neoplasms have more similar clinical features with intermediate trophoblastic tumors (ITTs). Total hysterectomy with lymph node dissection is recommended treatment for mixed gestational trophoblastic neoplasms, and chemotherapy should be used in patients with metastatic disease and with nonmetastatic disease who have adverse prognostic factors. PMID- 26261624 TI - Apoptosis in chronic cutaneous lupus erythematosus, discoid lupus, and lupus profundus. AB - INTRODUCTION: Lupus erythematosus is a multisystemic disease that is characterized by autoantibody production and immune complex deposition in such tissues as the mucosa, joints, the central nervous system, and skin. Cutaneous lupus erythematosus is categorized as acute, subacute, and chronic. Chronic cutaneous lupus erythematosus comprises discoid lupus erythematosus (DLE) and lupus profundus (LP). AIM: To analyze the expression of proapoptotic molecules in patients with lupus erythematosus discoid and lupus profundus. MATERIAL AND METHODS: Descriptive study, the study groups comprised 10 cases of LP and 10 cases of DLE, and a control. Skin samples of cases and controls were processed for immunohistochemistry and by TUNEL technique. The database and statistical analysis was performed (statistical test X(2)) SPSS (Chicago, IL, USA). RESULTS: Apoptotic features were broadly distributed along the skin biopsies in epidermal keratinocytes as well as at dermis. By immunohistochemistry the expression of Fas receptor and Fas-L was higher in the skin of lupus patients compared with controls. We also noted differences in Fas-L, -Fas, and -Bax proteins expression intensity in discoid lupus erythematosus patients in the epidermis, and hair follicles. CONCLUSIONS: Fas and Fas-L are expressed similarly in LP and DLE. PMID- 26261625 TI - Changes of monocyte subsets in patients with acute coronary syndrome and correlation with myocardial injury markers. AB - OBJECTIVE: To explore the changes of peripheral blood monocytes subsets in acute coronary syndrome (ACS) and its clinical significance. METHODS: A total of 68 ACS patients and 27 healthy subjects (HS) were enrolled. Monocyte subset analysis was performed using flow cytometry: CD14++CD16-(Mon1), CD14++CD16+ (Mon2), and CD14+CD16++ (Mon3). RESULTS: 1. The number of Mon1 and Mon3 were significantly increased in ACS patients compared with HS (P<0.05) and Mon2 decreased in ACS patients (P<0.05). 2. The number of Mon1, Mon2, Mon3 was positively correlated with WBC count (P<0.05). The Mon2% was negatively correlated with the serum levels of LDH, CK, CK-MB (P<0.05). The number of Mon1, Mon3 was positively correlated with the serum levels of LDH, CK, CK-MB (P<0.05). CONCLUSION: The changes in different subsets of monocytes may be associated with pathogenesis of ACS and myocardial injury. The findings might be useful in the assessment of myocardial injury. PMID- 26261626 TI - Up-regulation of soluble P-selectin predicates its prognostic value in patients with ankylosing spondylitis. AB - Ankylosing spondylitis (AS) is a chronic inflammatory disease with a high rate of disability. To find a proper prognosis marker is helpful for the treatment of AS. The purpose of this study was to investigate whether soluble P selectin (SP selectin) exerted effects on the prognosis of AS patients. Firstly, we detected the expression level of SP selectin in 85 AS patients and 60 normal subjects using quantitative real-time-polymerase chain reaction (QRT-PCR) assay. The result demonstrated that SP-selectin was over expressed in AS patients compared with healthy controls and the difference was significant (P < 0.05). Chi-square test was used to estimate whether SP selectin was associated with clinicopathologic characteristics. The factors of stages (P = 0.002), HLA-B27 (P = 0.002), ESR (P = 0.001) and C-reactive protein (P = 0.000) were considered to be related to the expression of SP selectin, which indicated that SP-selectin might be involved in the development of AS. Besides, the prognosis of AS patients after treatment was explored and analyzed via Cox regression analysis. The analysis suggested that ESR and SP selectin both served as independent prognostic biomarkers for AS (HR = 2.069, 95% CI = 1.049-4.080; HR = 4.562, 95% CI = 1.766 11.784). Taken together, our study revealed that not only the level of SP selectin was upregulated, but also SP selectin could predict the prognosis of AS patients. PMID- 26261627 TI - Relationship among maternal blood lead, ALAD gene polymorphism and neonatal neurobehavioral development. AB - Lead is a widely used heavy metal that can affect children's nervous system development. ALAD gene polymorphism is associated with lead neurotoxicity. This study aimed to clarify the relationship among maternal blood lead, ALAD gene polymorphism, and neonatal neurobehavioral development through detecting maternal blood lead and ALAD gene polymorphism. 198 maternal and neonatal were selected as the research object. Graphite furnace atomic absorption method was applied to detect the maternal blood lead concentration. PCR-RFLP was used to detect ALAD genotype distribution. Neonatal NANB score was treated as effect indicator. SPSS was used for statistical analysis. The ALAD genotype was 181 cases (91.4%) for ALAD11 and 17 cases (8.6%) for ALAD12. ALAD allele frequency distribution accords with genetics Hardy-Weinberg balance (P > 0.05). Blood lead level in maternal with ALAD12 genotype was significantly higher than with ALAD11 genotype (P < 0.01). NANB score in high blood lead neonatal group was obviously lower than the low blood lead group (P < 0.05). Newborn's NANB score from the maternal with ALAD11 genotype was lower than from the maternal with ALAD12 genotype (P < 0.01). After ruling out the confounding factors influence by multiple linear regressions, ALAD gene polymorphisms had no significant correlation with neonatal NANB score (P > 0.05). ALAD gene polymorphism is associated with the blood lead level. Low level lead exposure in utero may cause newborn early neurobehavioral maldevelopment. Maternal ALAD gene polymorphism can affect early neonatal neurobehavioral development by influencing the blood lead level. PMID- 26261628 TI - Differential microRNA expression in the serum of patients with nephrotic syndrome and clinical correlation analysis. AB - Many different microRNAs existed in nephrotic syndrome patients, and they may be involved in nephrotic syndrome occurrence. In order to further clarify miRNAs expression changes in nephrotic syndrome patients and their correlation with clinical features, this study investigated differential microRNA expression in the peripheral serum of patients with nephrotic syndrome and analyzed the correlation between miRNA with largest overexpression level and clinical features. miRNAs microarray was applied to screen different expressed miRNAs in nephrotic syndrome patients. Real-time PCR was performed to verify miRNA expression level. SPSS software was used to analyze correlation between miRNA expression and clinical features. Compared with healthy subjects, 35 miRNAs overexpressed and 24 miRNAs down-regulated in patients. After real-time PCR verification, 6 miRNAs up-regulated in nephrotic syndrome patients, including hsa miR-181a, hsa-miR-210, hsa-miR-30a, hsa-miR-942, hsa-miR-192 and hsa-miR-586. miRNA-30a significantly overexpressed in nephrotic syndrome patients and with no difference between genders. miRNA-30a expression level in drug resistant nephrotic syndrome patients was obviously higher than the drug sensitive patients. miRNA-30a up-regulated most significantly in mesangial proliferative glomerulonephritis among different pathology types, while it decreased most obviously in glomerular lesions. miRNA differently expressed in the serum of nephrotic syndrome patients. miRNA-30a could be treated as the molecular marker in predict drug resistance and pathological type of nephrotic syndrome. PMID- 26261629 TI - Detecting of gastric cancer by Bcl-2 and Ki67. AB - Gastric cancer is one of the most common malignant tumors and the second leading cause of cancer-related deaths in China. Although there is some progress in diagnose and treatment, the incidence of gastric cancer still keeps up increasing. In this study 40 patients with gastric cancer who underwent surgical operation is detected by immunohistochemistry. The positive rates of Bcl-2 and Ki67 protein expression in gastric cancer tissues were significantly higher than normal gastric mucous tissues. Correlation analysis showed that the expression of Bcl-2 is not correlated with that of Ki67. Positive expression of Bcl-2 or Ki67 did not correlate with age, gender, differentiation, stage and lymph node metastasis. These suggested that combination of Bcl-2 and Ki67 to detect gastric cancer is more effective. PMID- 26261630 TI - Association of the Trp316Ser variant (rs1801690) near the apolipoprotein H (beta2 glycoprotein-I) gene and serum lipid levels. AB - The objective of the present study was to detect the association of the Trp316Ser variant (rs1801690) near the apolipoprotein H (beta2-glycoprotein-I) gene and serum lipid levels in the Mulao and Han populations. A total of 879 subjects of Mulao and 844 subjects of Han Chinese were included. The levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and ApoA1 in Mulao, and triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), ApoA1 and the ratio of ApoA1/ApoB in Han were different among the three genotypes of the rs1801690 SNP (P < 0.05-0.01). Subgroup analyses showed that the levels of TC, TG, LDL-C, and ApoA1 in Mulao males; ApoA1 in Mulao females; TC, TG, HDL-C and ApoB and the ApoA1/ApoB ratio in Han males; and HDL-C, ApoA1 and the ApoA1/ApoB ratio in Han females were associated with the genotypes of rs1801690 (P < 0.05 0.001). Serum lipid parameters were also associated with several environmental factors (P < 0.05-0.001). The Trp316Ser variant (rs1801690) near the apolipoprotein H (beta2-glycoprotein-I) gene was associated with some serum lipid parameters in the two ethnic groups, but the trends of association suggest that the Trp316Ser variant (rs1801690) near the apolipoprotein H (beta2-glycoprotein I) gene might have racial/ethnic-and/or gender-specificity. PMID- 26261631 TI - Suppressor of cytokine signaling 3 A+930-->G (rs4969168) polymorphism is associated with apolipoprotein A1 and low-density lipoprotein cholesterol. AB - This study aimed to detect the association of the suppressor of cytokine signaling 3 gene (SOCS3) A+930-->G (rs4969168) single nucleotide polymorphism (SNP) and environmental factors with serum lipid levels in the Han and Mulao populations. Genotyping of the SOCS3 A+930-->G (rs4969168) SNP was performed in 752 of Han and 690 of Mulao participants using polymerase chain reaction and restriction fragment length polymorphism. The genotype and allele frequencies were significantly different between the Han and Mulao populations (GG, 57.71% vs. 51.16%, GA, 36.97% vs. 41.16%, AA, 5.32% vs. 7.68%, P = 0.023; G, 76.20% vs. 71.74%, A, 23.80% vs. 28.26%; P = 0.006; respectively). Serum apolipoprotein (Apo) A1 levels in Han were different among the genotypes (P < 0.05). Subgroup analyses showed that the levels of ApoA1 in Han females, and ApoA1 and low density lipoprotein cholesterol (LDL-C) in Mulao males were different among the genotypes (P < 0.05). Serum lipid parameters were also associated with several environmental factors in both ethnic groups (P < 0.05-0.001). These findings suggest that there may be a racial/ethnic- and/or sex-specific association between the SOCS3 A+930-->G (rs4969168) SNP and serum lipid parameters in some populations. PMID- 26261632 TI - Association of two polymorphisms in the FADS1/FADS2 gene cluster and the risk of coronary artery disease and ischemic stroke. AB - Little is known about the association of the FADS1/FADS2 SNPs and serum lipid levels and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Chinese southern population. The present study aimed to determine such association in the Chinese southern population. A total of 1,669 unrelated subjects (CAD, 534; IS, 553; and healthy controls, 582) were recruited in the study. Genotypes of the FADS1 rs174546 SNP and the FADS2 rs174601 SNP were determined by the SNaPshot Multiplex Kit. The T allele and TT genotype frequencies of the two SNPs were predominant in our study population. The T alleles were associated with increased risk of CAD and IS. Correspondingly, the C alleles were associated with reduced risk of CAD and IS. Haplotype analyses showed that the haplotype of T-T (rs174546-rs174601) was associated with an increased risk for IS, and the haplotype of C-C (rs174546-rs174601) was associated with a reduced risk for CAD and IS. The two SNPs were likely to influence serum lipid levels. The T allele carriers of the two SNPs and rs174601 TT genotype were associated with decreased serum HDL-C and ApoAI levels in the patient groups and with an increased risk of CAD and IS. The present study suggests that the FADS1 rs174546 SNP and the FADS2 rs174601 SNP are associated with the risk of CAD and IS, and are likely to influence serum lipid levels. However, further functional studies are needed to clarify how the two SNPs actually affect serum lipid levels and the risk of CAD and IS. PMID- 26261633 TI - Genetic variation in miR-100 rs1834306 is associated with decreased risk for esophageal squamous cell carcinoma in Kazakh patients in northwest China. AB - MicroRNAs (miRNAs) are a family of small noncoding RNAs that act as oncogenes and tumor suppressors. Single nucleotide polymorphisms (SNPs) in miRNAs may be associated with changes in phenotype and function. The aim of this study was to verify whether genetic variations in candidate microRNA (miRNA or miR) genes could contribute to esophageal squamous cell carcinoma (ESCC) susceptibility. A case-control study in 248 Kazakh patients with ESCC and 300 frequency matched control subjects was carried out to examine the potential association of six miRNA (miR-100 rs1834306, miR-34b/c rs4938723, miR-375 rs6715345, miR-146a rs2910164, miR-423 rs6505162 and miR-373 rs12983273) polymorphisms with risk of ESCC. We found that miR-100 rs1834306 T>C polymorphism was associated with a significant decreased risk of ESCC. In the recessive model, when the miR-100 rs1834306 TT/TC genotypes were used as the reference group, the CC homozygote genotype was associated with a significant decreased risk for ESCC (adjusted OR=0.495, 95% CI: 0.349-0.702, P=8.05*10(-5)). In the dominant model, when the miR-100 rs1834306 TT genotypes was used as the reference group, the TC/CC genotype were associated with a borderline statistically decreased risk for ESCC (adjusted OR=0.665, 95% CI: 0.430-1.031, P=0.067). In addition, the miR-100 rs1834306 C allele in the Kazakh population was significantly associated with decreased risk of ESCC (OR=0.609, 95% CI: 0.48-0.78, P=8.37*10(-5)). These findings indicated that functional polymorphism miR-100 rs1834306 C>T might contribute to decreased ESCC risk. PMID- 26261634 TI - Association of NCOA2 gene polymorphisms with obesity and dyslipidemia in the Chinese Han population. AB - BACKGROUND: Nuclear receptor coactivator 2 (NCOA2) gene plays an important role in adipogenesis and lipid metabolism. NCOA2 gene null mice exhibited less fat accumulation and lower serum lipid levels, and were protected against obesity. Few studies are known to have analyzed the association of NCOA2 gene single nucleotide polymorphisms with obesity and serum lipid profile. Our study aimed to evaluate the association of NCOA2 gene polymorphisms with the risk of obesity and dyslipidemia in the Chinese Han population. METHODS: Two NCOA2 gene polymorphisms (rs41391448 and rs10504473) were selected and genotyped in a Chinese Han cohort with 529 participants. The effect of different genotypes on BMI and serum lipid levels (TG, TC, LDL-C and HDL-C) was performed by the analysis of covariance. Association of NCOA2 polymorphisms with obesity and dyslipidemia was assessed by odds ratios (OR) and 95% confidence intervals (CI) under the unconditional logistic regression analysis. RESULTS: Significant association was observed between rs10504473 polymorphism and obesity under the recessive model (OR = 1.88, 95% CI 1.02-3.45, P = 0.047; adjusted OR = 1.87, 95% CI 1.02-3.44, P = 0.048). However, no association remained significant after Bonferroni correction. CONCLUSION: Our study suggests a possible association between NCOA2 rs10504473 polymorphism and obesity, and this SNP may influence the susceptibility of obesity in the Chinese Han population. PMID- 26261635 TI - Angiotensin type 1 receptor A1166C gene polymorphism is associated with endothelial dysfunction and in-stent restenosis after percutaneous coronary intervention. AB - BACKGROUND AND PURPOSE: Percutaneous coronary intervention (PCI) has been commonly used in the treatment of ischemic cardiovascular diseases, but the postprocedural in-stent restenosis (ISR) associated with altered endothelial functions has limited the clinical application of it; preventive medication with aspirin and statins has underlying adverse effects despite lowered risk of ISR. The purpose of this study was to investigate the role of angiotensin type 1 receptor (AT1R) A1166C gene polymorphisms in the development of endothelial dysfunction and ISR after PCI. METHODS: A total of 483 ST-segment elevation myocardial infarction (STEMI) patients undergoing PCI were prospectively genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism assay. The demographic, clinical, laboratory and angiographic parameters were recorded peri-procedurally and the patients were followed within 3 years. The flow-mediated dilation (FMD) was used to reflect the short-term changes in endothelial functions among different genotypes. The significance of AT1R gene polymorphisms in the development of ISR was analyzed using univariable and multivariable models. RESULTS: Amongst 483 patients, the distribution of the AT1R genotypes (AA, AC and CC) was associated with the levels of blood biomarkers of oxidative stress and deteriorated FMD after PCI (P<0.05). In univariable and multivariable logistic regression analysis, it was shown that AT1R CC genotype is strongly associated with the development of restenosis within 3 years after PCI (OR=3.736; P<0.001; calibrated OR=4.104; P<0.001). CONCLUSION: The CC AT1R genotype was associated with deteriorated endothelial functions in the target vessels of PCI and intermediate to long-term ISR. Our findings contribute to the foundation of genome-based prevention for high risk groups of cardiovascular diseases and pretreatment for the patients undergoing PCI. PMID- 26261636 TI - Associations of common SNPs in the SORT1, GCKR, LPL, APOA1, CETP, LDLR, APOE genes with lipid trait levels in an Algerian population sample. AB - Genome-wide association studies have identified many lipid-associated loci primarily in European and Asian populations. In view of the differences between ethnic groups in terms of the frequency and impact of these variants, our objective was to evaluate the relationships between eight lipid-associated variants (considered individually and in combination) and fasting serum triglyceride, total cholesterol, HDL- and LDL-cholesterol levels in an Algerian population sample (ISOR study, n = 751). Three SNPs (in SORT1, CETP and GCKR) were individually associated with lipid level variations. Moreover, the risk allele scores for total cholesterol, triglyceride and LDL-C levels (encompassing between three and six SNPs) were associated with their corresponding lipid traits. Our study is the first to show that some of the lipid-associated loci in European populations are associated with lipid traits in Algerians. Although our results will have to be confirmed in other North African populations, this study contributes to a better understanding of genetic susceptibility to lipid traits in Algeria. PMID- 26261637 TI - Association between the interaction of SMAD3 polymorphisms with body mass index and osteoarthritis susceptibility. AB - PURPOSE: This study aimed to investigate the relationship between the interaction of SMAD3 polymorphisms (rs12102171 and rs2289263) with body mass index (BMI) and osteoarthritis (OA) susceptibility. METHODS: This study involved 112 OA patients and 120 healthy people. The controls were frequency-matched with the cases by age and sex. Hardy-Weinberg equilibrium (HWE) was tested by chi(2) test in the control group. The rs12102171 and rs2289263 polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The relative risk of OA was represented by odds ratio (OR) with 95% confidence interval (CI) calculated by chi-squared test. Gene-environment interaction was analyzed by crossover analysis. RESULTS: The TT genotype and T allele of SMAD3 rs12102171 polymorphism were more frequent in case than control groups (P=0.04 in both of two polymorphisms), which increased the risk of OA (OR=3.39, 95% CI=1.03-11.11 and OR=1.64, 95% CI=1.03-2.59). GG genotype and G allele were also the risk factors for OA (OR=3.22, 95% CI=1.09-9.51 and OR=1.57, 95% CI=1.02-2.42). The BMI had interactions with genotype CC and CT+TT of rs12102171 and TT and TG+GG of rs2289263 (rs12102171: OR=2.15, P=0.02 and OR=3.99, P=1.00*10(-3); rs2289263: OR=2.73, P=4.00*10(-3) and OR=4.67, P=0). CONCLUSIONS: CC and CT+TT and TT and TG+GG genotypes of SMAD3 rs12102171 and rs2289263 polymorphisms together with BMI may be susceptible factors to OA, and interactions there between can possibly confer risk to OA. PMID- 26261638 TI - Correlation between exon 3 polymorphism of growth hormone receptor gene and the responses to rhGH therapy. AB - OBJECTIVE: To investigate the correlation between the exon 3 polymorphism of growth hormone receptor (GHR) gene and the responses to the recombinant human growth hormone (rhGH) therapy in children with short stature. METHODS: Forty-five growth hormone deficiency (GHD) children (male: 30, female: 15, aged 10.39 +/- 2.73 yrs) and twenty-five idiopathic short stature (ISS) children (male: 15, female: 10, aged 10.58 +/- 2.56 yrs) admitted to our hospital were included. The polymorphism of exon 3 of GHR gene was determined using multiple PCR amplification. Treatment duration for each subject was at least 12 months. On this basis, we evaluated the correlation between treatment efficiency of rhGH therapy and GHR exon 3 polymorphism, GHD, and treatment duration. RESULTS: Significant difference was noted in the growth velocity (GV) of GHD children with a genotype of GHRfl compared with those with a genotype of GHRd3 (9.44 +/- 2.35 vs. 11.36 +/- 2.49, P < 0.05). Meanwhile, the GV of ISS patients with a genotype of GHRfl were remarkably decreased compared with those with a genotype of GHRd3 (8.74 +/- 2.36 vs. 11.18 +/- 2.44, P < 0.05). For the children with peak GH response of less than 5 ng/ml, statistical difference was noted in the GV of children with a genotype of GHRfl compared with those with a genotype of GHRd3 (9.55 +/- 2.76 vs. 10.84 +/- 1.53, P < 0.05). For the patients with peak GH response to clonidine or pyridostigmine bromide of > 5 ng/ml, a satisfactory response to rhGH therapy was noted in children with a genotype of GHRd3 compared with those of GHRfl (P < 0.05). CONCLUSIONS: GHRd3 was correlated with the response to rhGH therapy in children with short stature. For the patients with the same genotype, GHD caused no obvious effects on the final height. However, for the patients with peak GH response of > 5 ng/ml, a satisfactory response to rhGH therapy was noted in children with a genotype of GHRd3 compared with those of GHRfl (P < 0.05). A higher treatment efficiency was obtained in those received rhGH at an early age. PMID- 26261639 TI - Interleukin-17A gene polymorphism is associated with susceptibility to gastric cancer. AB - We conducted a study to investigate the role of three common SNPs in the IL-17A and IL-17F genes (rs2275913G>A, rs3748067C>T and rs763780T>C) in the development of gastric cancer, and their interaction with H.pylori infection. A total of 326 patients with gastric cancer and 326 control subjects were consecutively recruited between May 2012 and May 2014. Genotyping of IL-17A rs2275913G>A and rs3748067C>T and IL-17F rs763780T>C was performed in a 384-well plate format on the Sequenom MassARRAY platform. By logistic regression analysis, individuals carrying the GA and AA genotypes of IL-17 rs2275913G>A were significantly associated with an increased risk of gastric cancer when compared with GG genotype, and the adjusted Ors (95% CI) were 1.46 (1.03-2.06) for GA genotype and 2.57 (1.51-4.43) for AA genotype. We observed that the GA+AA genotype of rs2275913 was associated with an increased risk of gastric cancer among H.pylori infection subjects (OR=2.21, 95% CI=1.29-3.79). In conclusion, we found that there was a significant association between L-17A rs2275913G>A polymorphism and increased gastric cancer risk, especially in H.pylori infection subjects. PMID- 26261640 TI - Total ginsenosides synergize with ulinastatin against septic acute lung injury and acute respiratory distress syndrome. AB - Total ginsenosides synergize with ulinastatin (UTI) against septic acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). We randomly divided 80 cases of severe sepsis-induced ALI and ARDS into a UTI group and a ginsenosides (GS)+UTI group. Continuous electrocardiac monitoring of pulse, respiratory rate, blood pressure, and heart rate; invasive hemodynamic monitoring; ventilator-assisted breathing and circulation support; and anti infection as well as UTI treatment were given in the UTI group with GS treatment added for 7 consecutive days in the GS+UTI group. The indicators of pulmonary vascular permeability, pulmonary circulation, blood gases, and hemodynamics as well as APACHE II and ALI scores were detected on days 1, 3, and 7. The ALI score in the GS+UTI group was significantly decreased (P < 0.05) compared with that of the UTI group, and the indicators of pulmonary capillary permeability such as pulmonary vascular permeability index, extravascular lung water index, and oxygenation index, in the GS+UTI group improved significantly more than that of the UTI group. The indicators of hemodynamics and pulmonary circulation such as cardiac index, intrathoracic blood volume index, and central venous pressure improved significantly (P < 0.05), and the APACHE II score in the GS+UTI group was lower than that of the UTI group. GS can effectively collaborate with UTI against ALI and/or ARDS. PMID- 26261641 TI - Association between ACE polymorphisms and osteoarthritis susceptibility. AB - OBJECTIVE: The present study was designed to investigate the association of angiotensin-converting enzyme (ACE) rs4343 and rs4362 polymorphisms with the susceptibility to osteoarthritis (OA). METHODS: 109 knee OA patients and 114 healthy people were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to perform the genotyping for two groups and the linkage disequilibrium and haplotype were analyzed using Haploview software. The differences of genotype and allele frequencies were analyzed by chi(2) test and Fisher's exact test. The relationship between ACE polymorphisms and OA susceptibility was represented by odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: The genotypes distributions of ACE rs4343 and rs4362 polymorphisms in control groups were accordance with HWE. ACE rs4343 polymorphism was associated with the significantly increased risk of OA (AG vs. AA: OR=2.41, P=0.003; GG vs. AA: OR=5.35, P=0.015; G vs. A: OR=2.27, P<0.001). Similarly, rs4362 polymorphisms was also a risk factor for OA (CT vs. CC: OR=2.60, P=0.005; TT vs. CC: OR=3.15, P=0.003; T vs. C: OR=1.88, P=0.001). The result of haplotype analysis showed complete linkage disequilibrium in rs 4343 and rs 4362 polymorphisms. The G-T haplotype significantly increased OA susceptibility, but A-C is a protective factor for the occurrence of OA. CONCLUSION: Significant correlation exists between ACE rs4343 and rs4362 polymorphisms and OA. In haplotype analysis, A-C haplotype may provide protection against OA, and G-T haplotype may be a risk factor for the development of OA. PMID- 26261642 TI - MTHFR genetic polymorphism increases the risk of preterm delivery. AB - AIMS: This study aimed to investigate the association between the methylene tetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms and premature delivery susceptibility. METHODS: With matched age and gender, 108 premature delivery pregnant women as cases and 108 healthy pregnant women as controls were recruited in this case-control study. The cases and controls had same gestational weeks. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was adopted to analyze C677T and A1298C polymorphisms of the participants. Linkage disequilibrium (LD) and haplotype analysis were conducted by Haploview software. The differences for frequencies of gene type, allele and haplotypes in cases and controls were tested by chi-square test. The relevant risk of premature delivery was represented by odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: TT gene type frequency of C677T polymorphsim was higher in cases than the controls (P=0.004, OR=3.077, 95% CI=1.469-6.447), so was allele T (P=0.002, OR=1.853, 95% CI=1.265-2.716). Whereas, CC gene type of A1298C polymorphism had a lower distribution in cases than the controls (P=0.008, OR=0.095, 95% CI=0.012-0.775), so was allele C (P=0.047, OR=0.610, 95% CI=0.384-0.970). Haplotype analysis and linkage disequilibrium test conducted on the alleles of two polymorphisms in MTHFR gene, we discovered that haplotype T-A had a higher distribution in cases, which indicated that susceptible haplotype T-A was the candidate factor for premature delivery. CONCLUSIONS: Gene type TT of MTHFR C677T polymorphism might make premature delivery risk rise while gene type CC of A1298C polymorphism might have protective influence on premature delivery. PMID- 26261643 TI - Correlation between the interactions of ABCA4 polymorphisms and smoking with the susceptibility to age-related macular degeneration. AB - OBJECTIVE: Our study was aimed to analyze the relationship between retina specific ATP-binding cassette, sub-family A, member 4 (ABCA4) gene polymorphisms and gene-environment interactions with age-related macular degeneration (AMD) susceptibility. METHODS: 98 AMD patients and 110 healthy controls, matched in age and sex, were enrolled in this study. ABCA4 polymorphisms (2633C>A, 5646G>A and 6389T>A) were determined by direct sequencing. Differences of genotype and allele distributions were analyzed by chi(2) test. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were adopted to represent the relative risk of AMD. Gene environment interactions were analyzed using crossover analysis. RESULTS: 2633C>A polymorphism had no obvious correlation with AMD risk. Genotype AA and allele A in 5646G>A polymorphism significantly increased the risk of AMD (OR=4.753, 95% CI=1.249-18.085; OR=1.944, 95% CI=1.209-3.126). 6389T>A polymorphism AA genotype had no significant correlation with AMD risk, but the A allele distinctly enhanced the AMD risk (OR=1.681, 95% CI=1.071-2.639). Afterwards, we analyzed the interactions between ABCA4 polymorphisms and smoking on AMD. Smoking had interactions with all of 2633C>A (CC+CA), 5646G>A and 6389T>A polymorphisms, and the interactions were significantly correlated with AMD. CONCLUSIONS: 2633C>A (CC+CA) genotype, 5646G>A and 6389T>A polymorphisms of ABCA4 gene and smoking are susceptible factors for AMD, and the interactions of ABCA4 polymorphisms with smoking increased the risk of AMD. PMID- 26261644 TI - Association between interferon gamma 13-CA-repeats polymorphism and metastasis of nasopharyngeal carcinoma in a population of Northern China. AB - Interferon Gamma gamma (IFN-gamma) 13-CA-repeats polymorphism is associated with a variety of diseases; here we report its association with nasopharyngeal carcinoma (NPC) metastasis in a retrospective analysis of a cohort of 220 NPC patients in the northern China. The results showed that the distributions of CA13 /CA13-genotypes were significantly higher in the patients with lymph node metastasis (P<0.05) and distant metastasis (P<0.001); there was a significant difference between NPC patients with stage I+II and those with stage III+IV regarding CA13+/CA13-(P<0.001) and CA13-/CA13- genotypes (P<0.001); further analysis showed a more pronounced difference between NPC patients with stage I+II+III and those with stage IV for CA13-/CA13-genotype (P<0.001), whereas no difference was found for CA13+/CA13- genotype (P=0.790). Thus, we identify that IFN-gamma 13-CA-repeat polymorphism is significantly associated with the metastasis of NPC, which may provide insights into its prognosis and individualized treatment. PMID- 26261645 TI - Association between TRAIL gene polymorphisms and the susceptibility and severity of lumbar disc degeneration. AB - AIM: The aim of the present study was to investigate the association between tumor necrosis factor related apoptosis-inducing ligand (TRAIL) gene polymorphisms and the susceptibility and severity of lumbar disc degeneration (LDD) in the Chinese Han population. METHODS: A total of 153 patients with LDD and 131 healthy subjects were enrolled in the study. Four single-nucleotide polymorphisms (SNPs) in the 3' untranslated region (3'UTR) of TRAIL gene, including 1289 C/A, 1525 G/A, 1588 G/A and 1595 C/T, were genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: The genotypes and alleles frequencies of TRAIL at 1525 and 1595 positions in all subjects were the same. There was a significant association between TRAIL 1525/1595 polymorphisms and the susceptibility of LDD. The frequencies of 1525 GG /1595 CC genotype, and 1525 G/1595 C allele were higher in the patients group than that in the control group. In addition, we found patients with the 1525 AA /1595 TT genotype, as well as 1525 A/1595 T allele exhibit significantly low frequency of high grades of disc degeneration. However, there were no significant differences in the genotype or allele distribution of TRAIL 1289 C/A or 1588 G/A between the patients and the control group. CONCLUSION: TRAIL 1525/1595 polymorphisms were associated with the susceptibility and severity of LDD in the Chinese Han population. PMID- 26261646 TI - Association between CTLA-4 gene polymorphism and ankylosing spondylitis: a case control study. AB - AIMS: The aim of our study was to evaluate the association between CTLA-4 polymorphisms (+49A/G, -318C/T and CT60A/G) and ankylosing spondylitis (AS) susceptibility. METHODS: A total of 120 AS cases and healthy controls, matched on the age and gender, were enrolled in the study. Polymerase chain reaction restriction fragment length polymorphisms (PCR-RFLP) were used to determine the gentypes of +49A/G, -318C/T and CT60A/G polymorphisms. Genotype distribution in control group was assessed by Hardy Weinberg Equilibrium (HWE) test. Odds ratio (OR) with 95% confidence interval (95% CI) were adopted to evaluate the relationship of CTLA-4 polymorphisms and AS susceptibility. RESULTS: In our study, genotype distribution of the three polymorphisms in control group was consistent with the HWE (P > 0.05). The genotype analysis showed that AA genotype of + 49A/G polymorphism could increase the risk for AS (OR=2.357, 95% CI=1.127 4.930). Moreover, the frequency of A allele was also presented as a risk factor for AS. Additionally, AA genotype and A allele of CT60A/G appeared to be related with AS susceptibility (OR=2.610, 95% CI=1.047-6.510; OR=1.751, 95% CI=1.160 2.641). However, the T allele of -318C/T appeared to be a protective factor for AS (OR=0.383, 95% CI=0.228-0.643). CONCLUSION: In summary, there existed significant association between CTLA-4 gene polymorphisms and increased or decreased risk for AS. PMID- 26261647 TI - Correlation between survivin genetic polymorphisms and lung cancer susceptibility. AB - AIMS: The purpose of the study was to analyze the relationship of survivin polymorphisms including -31G/C, -625G/C, 9194A/G and 9809T/C with the susceptibility to lung cancer. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to test the polymorphisms of 31G/C, -625G/C, 9194A/G and 9809T/C in 104 patients with lung cancer and 104 healthy controls. Then, linkage disequilibrium and haplotypes were analyzed by HaploView software. The differences of genotype, allele and haplotype frequencies in case and control group were assessed via chi-square test. Odds ratio (OR) with 95% CI were used to evaluate the correlation of survivin polymorphisms with lung cancer. RESULTS: Genotype distribution of each polymorphism site in control group was in agreement with Hardy-Weinberg equilibrium (HWE) (P>0.05). The frequency of -31G/C CC genotype and C allele in case group were much higher than that of controls, respectively (CC: 33.6% vs. 22.1%; C: 57.2% vs. 46.6%) and CC genotype as well as C allele were appeared to be risk factors for lung cancer. Meanwhile, 9194A/G GG genotype could increase the risk for lung cancer (OR=2.86, 95% CI=1.14 7.20). The risk of G allele carriers for lung caner was higher than that of A allele (OR=1.63, 95% CI=1.08-2.47). The haplotypes analysis indicated that CGGC and GCAT were associated with the susceptibility to lung cancer (OR=2.79, 95% CI=1.58-4.92; OR=2.36, 95% CI=1.29-4.30). CONCLUSIONS: Survivin -31G/C and 9194A/G polymorphisms were associated with the risk of lung cancer. The CGGC and GCAT haplotypes carriers were more likely to develop lung cancer. PMID- 26261648 TI - Relevance between HLA-DP gene rs2281388 polymorphism and hepatocellular carcinoma risk. AB - PURPOSE: We carried out this study to find out the relevance between rs2281388 T/C polymorphism of human leukocyte antigen (HLA) gene and hepatocellular carcinoma (HCC) risk in Chinese Han population. METHODS: The method of polymerase chain reaction (PCR) was applied to amplify the genomic DNA. Then the PCR products were sequenced to test the HLA-DP gene rs2281388T/C polymorphism of the case and control groups. Odds ratios (ORs) and 95% confidence interval (95% CIs) were utilized to evaluate the potential correlation between rs2281388 variants and HCC risk. RESULTS: We analyzed the rs2281388 polymorphism distribution among the clinical pathological features. The results showed that there existed a significant statistic correlation between rs2281388T/C polymorphism of HLA-DP gene and HBsAg feature, and no significant correlation was found between rs2281388 and other clinical features. Further analysis showed that the TT genotype of rs2281388 was significantly correlated with HCC risk, and the same to T allele, but there was no significant difference of CT genotype distribution in case and control groups. CONCLUSION: TT genotype and T allele of HLA-DP gene rs2281388 polymorphism may increase the risk of HCC. PMID- 26261650 TI - Association between 8473T>C polymorphism in the cyclooxygenase-2 gene and the risk of nasopharyngeal carcinoma. AB - BACKGROUND: No studies have examined the relationship between COX-2 8473T>C polymorphism and the risk of nasopharyngeal carcinoma in Chinese population. MATERIAL AND METHODS: 296 patients with nasopharyngeal carcinoma and 300 age and gender-matched healthy controls recruited were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Cancer risk associated with the genotypes was estimated as odds ratios (ORs) and 95% confidence intervals (95% CIs) using unconditioned logistic regression. RESULTS: There was significant difference in the distribution of COX-2 8473T>C polymorphism genotype between nasopharyngeal carcinoma patients and healthy controls (P=0.027). When the TT genotype was used as the reference group, the CC genotype was associated with significantly decreased risk for nasopharyngeal carcinoma (adjusted OR=0.67, 95% CI=0.33-0.83; P=0.01). Under the recessive model of inheritance, the CC genotype was associated with significantly decreased risk for nasopharyngeal carcinoma (adjusted OR=0.43, 95% CI=0.37-0.81; P=0.007). Furthermore, the C allele was associated with significantly decreased risk for nasopharyngeal carcinoma (adjusted OR=0.48, 95% CI=0.39-0.85; P=0.009). CONCLUSION: These data suggested that COX-2 8473T>C polymorphism was associated with reduced risk of nasopharyngeal carcinoma. PMID- 26261649 TI - Association between MDM2 rs769412 and rs937283 polymorphisms with alcohol drinking and laryngeal carcinoma risk. AB - TARGET: To investigate the association between the interactions of murine double minute 2 (MDM2) polymorphisms (rs769412 and rs937283) with alcohol drinking and laryngeal carcinoma. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the genotypes status of MDM2 rs769412 and rs937283 polymorphisms among 126 cases and 120 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by the chi-squared test, which was adopted to analyze the association between MDM2 rs769412 and rs937283 polymorphisms and the susceptibility to larynx carcinoma in the drinking population. RESULTS: Genotypes distributions of MDM2 rs769412 and rs937283 polymorphisms in the control group were in accordance with Hardy-Weinberg equilibrium (HWE). MDM2 rs769412 GG genotype and G allele significantly increased laryngeal carcinoma risk (GG vs. AA: OR=3.17, 95% CI=1.25-8.04; G vs. A: OR=1.88, 95% CI=1.24-2.84). Furthermore, the mutant genotypes of MDM2 rs937283and rs769412 were remarkablely associated with the increased risk for laryngeal carcinoma in drinking population (rs937283: OR=2.67, 95% CI=1.40-5.07; rs769412: OR=3.76, 95% CI=1.62-8.75). CONCLUSION: MDM2 polymorphisms are correlated with the onset of laryngeal carcinoma. The relationship is strengthened by alcohol drinking. PMID- 26261651 TI - Klotho gene polymorphisms are related to colorectal cancer susceptibility. AB - AIM: The purpose of this study was to investigate the relationship of Klotho gene G-395A and C1818T polymorphisms with colorectal cancer (CRC) susceptibility. METHODS: 125 CRC patients and 125 controls were enrolled in the study. G-395A and C1818T polymorphisms were genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology. Haploview software was utilized to conduct linkage disequilibrium and haplotype analysis. Odds ratio (OR) and 95% confidence interval (95% CI) were used to analyze the correlation of genotypes and haplotypes with CRC susceptibility. RESULTS: AA and GA genotypes of G-395A polymorphisms were related with CRC risk (AA: OR = 4.161, 95% CI = 1.437 12.053; GA: OR = 1.958, 95% CI = 1.133-3.385). The frequency of A allele was much higher in case group, compared with controls (31.2% vs.17.6%) and the value of OR AND 95% CI suggested that A allele served as a risk factor for CRC (OR = 2.123, 95% CI = 1.393-3.236). Haplotypes analysis indicated that A-C and A-T haplotypes were significantly associated with risk of CRC (OR = 1.822, 95% CI = 1.124-2.954; OR = 2.877, 95% CI = 1.340-6.176). CONCLUSION: G-395A polymorphism of Klotho gene could increase the risk of CRC. PMID- 26261652 TI - Distant dissemination of mixed low-grade astroblastoma-arteriovenous malformation after initial operation: a case report. AB - We present a rare case of low-grade astroblastoma coexisting with an arteriovenous malformation (AVM) underwent surgery two times in a 38-year-old man. After the first surgery, this case was reported as a mixed low-grade astroblastoma and AVM. The lesion was completely resected surgically along with AVM. The patient underwent postoperative radiotherapy. Twenty months later, MRI showed enhanced lesions in suprasellar, pineal region and multiple small lesions in the spinal cord, whereas completely no recurrent lesion at the primary tumor site. So, the patient rationally underwent surgical removal in suprasellar and pineal region. After the second surgery, this case was diagnosed as a high-grade astroblastoma. Cells from the second surgical specimens showed high MIB-1 index and an increased olig-2 index. In addition, it is not common for low-grade astroblastoma metastasis to suprasellar, pineal region and spine with completely no recurrence at the original primary tumor site. Therefore it is difficult to predict tumor behavior and patient's clinical outcome merely based on histologic features. The important issue is whether the AVM was thought to be the cause of poor progress of this tumor. More cases are needed to confirm this. Classification and histogenesis of this tumor is still debated. Lack of clinicopathological correlation makes the prognosis of this tumor unpredictable. Anyway, we should be very discreet to treat the astroblastoma, even for low-grade astroblastoma. PMID- 26261653 TI - Atrophic dermatofibrosarcoma protuberans with the fusion gene COL1A1-PDGFB detected by RT-PCR using only a single primer pair. AB - Dermatofibrosarcoma protuberans (DFSPs) is an uncommon dermal tumor of intermediate to low-grade malignancy. A few patients have clinically persistent plaques that might be atrophic, and they are difficult to be diagnosed clinically. With the development of cytogenetic and molecular biology techniques, the detection of fusion transcripts of the collagen type 1a1 (COL1A1) and platelet-derived growth factor-BB (PDGFB) genes has been recognized as a reliable and valuable molecular tool for the diagnosis of DFSPs. We reported a 24-year-old woman who had a 2 years history of atrophic DFSPs, and detected the gene fusion between COL1A1 to PDGFB by one-step method of RT-PCR using only a single primer pair. The gene fusion detected by this rapid and efficient one-step method in our patient appears to be the first report of atrophic DFSPs, and we detected a novel COL1A1 breakpoint between exon 2 and exon 3. PMID- 26261654 TI - Carcinosarcoma of the gallbladder: a case report and review of the literature. AB - Carcinosarcoma of the gallbladder is a rare malignancy characterized by malignant epithelial and mesenchymal components. The disease usually presents at an advanced stage, and as a result, curative resection is uncommon. This report describes a case that underwent curative resection. We herein declare the case of a patient in a 62-year-old male, with carcinosarcoma of the gallbladder with chondroid differentiation. The patient is treated by a simple cholecystectomy, a wedge resection of the underlying liver tissue and the pericholedochal lymph nodes for a tumor which occupied the entire gallbladder. Histologically, the epithelial component of the tumor was composed of adenocarcinoma and the mesenchymal component was composed of fibrosarcoma. The tumor was identified as extend to the serosa tissue and to have metastasized to no lymph node. The prognosis of carcinosarcoma of the gallbladder remains poor despite curative resection, and thus, the authors recommend that effort should be made to improve surgical outcomes. The patient survived 13 months and is still alive today. PMID- 26261655 TI - An unusual case of colonic adenocarcinoma development in the region of disseminating lobular breast carcinoma infiltration: diagnostic approach and review of the literature. AB - We present an unusual case of colon cancer development in bowel segment involved with lobular breast carcinoma infiltration. 80 year old Caucasian woman was diagnosed with right colon carcinoma due to rectal bleeding and obstructive symptoms. She had nine years clinical history of lobular, well differentiated breast cancer with five years of postoperative tamoxifen therapy, disseminating to bones and pleural cavities two years prior to hemicolectomy. On microscopic examination under the colonic adenocarcinoma and in the whole length of the resected bowel segment, massive infiltration of lobular carcinoma was discovered. She remains alive under the palliative hormone and chemotherapy. In our paper we discuss clinical and pathological issues concerning metastases of breast cancer into the gastrointestinal tract as well as rare colocalization of colonic and breast cancers within the same intestinal segment. Review of the literature is also presented accordingly. PMID- 26261656 TI - Transition between morule-like and solid components may occur in solid predominant adenocarcinoma of the lung: report of 2 cases with EGFR and KRAS mutations. AB - A limited number of pulmonary adenocarcinoma cases with morule-like components have been described to date, and the most frequent histological subtype is papillary-predominant adenocarcinoma. Occasionally, this type of adenocarcinoma is associated with solid-predominant adenocarcinoma. EGFR mutations are predominant in adenocarcinoma with morule-like components, followed by ALK rearrangements. Herein, we present 2 cases of solid-predominant adenocarcinoma with morule-like components harboring either an EGFR or KRAS mutation. This KRAS mutant case is the first to be associated with morule-like components, to the best of our knowledge. Both cases showed transition between micropapillary and morule-like components. Transition between morule-like and solid components was also observed in both cases. Although a few cases of solid-predominant adenocarcinoma have been shown to harbor morule-like components, this type of transition has not been previously well described. We surmised that the solid components of some EGFR-mutant adenocarcinomas might be derived from morule-like components. PMID- 26261657 TI - Nodular pulmonary amyloidosis and obvious ossification due to primary pulmonary MALT lymphoma with extensive plasmacytic differentiation: Report of a rare case and review of the literature. AB - Localized (primary) pulmonary amyloidosis associated with pulmonary low-grade B cell lymphoma is rarely occurred. Here we report an unusual case of nodular pulmonary amyloidosis and obvious ossification due to primary pulmonary mucosa associated lymphoid tissue (MALT) lymphoma with extensive plasmacytic differentiation in a 59-year-old man; moreover, two bronchial lymph nodes were involved histologically. The patient underwent a left lower lobectomy along with mediastinal lymphadenectomy. He received no adjuvant therapy and the postoperative course was uneventful within the 14 months follow-up period after his initial diagnosis. PMID- 26261658 TI - Primary small cell cancer of cervical trachea: a case report and literature review. AB - Primary small cell carcinoma of trachea is even more uncommon and only a few cases have been reported. Our search revealed only 90 cases in the English language literatures. CASE REPORT: we report a case of cervical tracheal small cell cancer. A 67-year-old male presented with over 2-month history of cough and dyspnea. CT and MRI revealed a 1.0 cm * 2.5 cm intraluminal, irregular soft tissue mass in the upper trachea, approximately 2.5 cm below the glottis. A bronchoscopic examination disclosed a large tumor in the cervical trachea and the lesion occupied more than 60% of the tracheal lumen. Cytological examination suggested some poorly differentiated carcinoma cells. The patient received concurrent chemoradiotherapy and did not perform surgery. One week after CCR, the patient occurred difficulty in breath and tracheal stent was implanted. The symptom was improved markedly. Four days after implant of tracheal stent, the patient presented irritable cough and hemoptysis. The amount of bleeding was about 300 ml. The hemorrhage stopped by treatment of vasoconstrictor and fresh plasma. However, two days later, hemoptysis was continuing even if treatment of vasoconstrictor and fresh plasma. The patient and relatives waived the further therapies. The patient died of massive hemoptysis one week out of hospital. CONCLUSIONS: The tracheal small cell cancer is rare. The optimal treatment is unclear. In general, the strategy is introduced concurrent chemoradiotherapy following as small cell lung cancer. In cervical trachea, we suggest that surgical resection should be performed followed by postoperative adjuvant therapy. PMID- 26261659 TI - Detection of t(12;14)(p13;q32) in a patient with IGH-CCND1 negative mantle cell lymphoma resembling ultra-high risk chronic lymphocytic leukemia. AB - T(12;14)(p13;q32) is a rare recurrent chromosomal translocation, which has only been identified in a small subgroup of mantle cell lymphoma (MCL) without typical t(11;14)(q13;q32). This rearrangement causes aberrant over-expression of cyclin D2 (CCND2), which disrupts the normal cell cycle. Here we report a subtle case of MCL with t(12;14)(p13;q32) that was initially misdiagnosed as ultra-high risk chronic lymphocytic leukemia (CLL). A 60-year-old male patient presented with obvious leukocytosis and progressive weakness. Morphology of peripheral blood and immunophenotyping by flow cytometry pointed to a diagnosis of chronic lymphocytic leukemia. Fluorescence in situ hybridization (FISH) using IGH-CCND1 probe was negative for CCND1 abnormality, but demonstrated IGH breakapart signals. The initial diagnosis of CLL was established and the patient was treated with six courses of immunochemotherpy with fludarabine, cyclophosphamide and rituximab (FCR). Complete remission (CR) was achieved at the end of treatment, but disease relapsed quickly. The patient was transferred to our hospital, flow cytometry using additional markers showed that the clonal cells were CD200+(dim), CD148+(strong), and chromosome analysis revealed a complex karyotype, 47, XY, t(12;14)(p13;q32), +12, del(9p21), which indicated over-expression of CCND2, and immunostaining showed strong positivity of SOX11 further confirming the characteristics of CCND1-negtive MCL. The final diagnosis was revised to rare subtype of MCL with CCND2 translocation and intensive regimens were employed. This confusable MCL case illustrates the importance of cytogenetic analysis and clinicopathologic diagnosis of this rare category of MCL. PMID- 26261660 TI - Invasive cystic hypersecretory carcinoma of the breast: a case report. AB - PURPOSE: To report a new case of invasive cystic hypersecretory carcinoma. The clinical and pathological characteristics of the lesion and a review of the literature are both described. METHODS: A descriptive study of a case of invasive CHC occurring in a 60-yr-old woman is presented. Tumor was standard processed and stained by hematoxylin & eosin, PAS, immunohistochemically examined for ER, PR, C erbB-2, CEA, thyroglobulin, E-cadherin, S-100 protein, and Cytokeratin5/6. RESULTS: The tumor, which was 4.7*3.7*3.0 cm, was localized in the upper region of the left breast. This tumor revealed multiple cystic spaces, which were filled with PAS. It was positive for CEA, ER, E-cadherin, and S-100 protein, but negative for thyroglobulin, PR, and C-erbB-2. Cytokeratin5/6 was expressed in the cystic hypersecretory hyperplasia region, but not in the invasive area. The ten month follow-up period was uneventful. CONCLUSIONS: Cystic hypersecretory carcinoma of the breast is a rare and distinctive variant of ductal carcinoma in situ. It has the potential for invasive growth. As there are few recorded cases, the prognosis in patients with invasive CHC is still uncertain and a matter of intensive debate. PMID- 26261661 TI - A case of Peutz-Jeghers syndrome associated with high-grade intramucosal neoplasia. AB - Peutz-Jeghers syndrome (PJS) is a rare, inherited autosomal dominant disease characterized by mucocutaneous pigmentation and polyps in the gastrointestinal tract. Here, we report the rare case of a 64-year-old female patient with pigmentation on her lips and extremities for over 63 years and intermittent abdominal pain and, diarrhea for 3 years. The presence of intestinal and colorectal hamartomatous polyps was confirmed. The removal and characterization of her rectal polyp showed it to be a typical hamartomatous polyp with a portion of it being an adenoma with high-grade intramucosal neoplasia. A survey of the patient's family identified 9 people in the family with Peutz-Jeghers syndrome and three of them have already died from colorectal cancer. This case study serves as an example of how imperative it is to survey the patient about their family history in order to detect early cancerous lesions. PMID- 26261662 TI - Phosphaturic mesenchymal tumour mixed connective tissue variant: report of three cases with unusual histological findings. AB - Phosphaturic mesenchymal tumour mixed connective tissue variant (PMTMCT) is a rare tumour occurring in bone and soft tissue that usually behaves in a benign manner. Elaboration of biologically active substances by this tumour gives rise to a paraneoplastic syndrome known as oncogenic osteomalacia, manifesting clinically as bone pain, generalized weakness and pathological fractures. Recognition of PMTMCT and its associated syndrome is important, as resection of the tumour in most instances results in prompt resolution of symptoms. Previously reported cases of this tumour have emphasized the consistent presence of certain histological features that are considered prerequisite for making the diagnosis of PMTMCT. We describe three cases of PMTMCT, of which two first presented with progressive symptoms of osteomalacia and one remained clinically silent aside from the symptom of a palpable lump. Our cases highlight the wide-ranging histological patterns displayed by these tumours, and draw attention to certain microscopic findings that until now have been given little if any mention. Tentacular growth pattern and satellite nodules appear to be common findings in PMTMCTs, and can make complete surgical excision of these tumours challenging. The ability of this otherwise histologically benign tumour to permeate vascular spaces has to our knowledge never been described previously. One tumour lacked the characteristic calcifying matrix of PMTMCT, suggesting that in some tumours this defining feature may be focal if not entirely absent. PMTMCT shares features with and can resemble a variety of bone and soft tissue neoplasms, requiring the surgical pathologist to be familiar with this entity. PMID- 26261663 TI - An autopsy case of pneumococcal Waterhouse-Friderichsen syndrome with possible functional asplenia/hyposplenia. AB - We report an autopsy case of rapid progressive Waterhouse-Friderichsen syndrome (WFS) associated with Streptococcus pneumonia infection in a previously healthy man. Although he once visited a hospital about 6 hours before death, the both physical and serological examination did not show any sign of overwhelming infection. Autopsy showed massive adrenal hemorrhage without inflammation, and showed proliferation of gram positive cocci and microthrombosis in the vessels of many organs. The pathological change of respiratory tract was extremely minimal. Size and weight of the spleen possible decreased than normal. However, histological examination showed that obscuration of germinal center and decreasing the immunological cells of mantle and marginal zone. Immunohisitochemically, marked decreasing the marginal zone macrophages, which are positive for specific intercellular adhesion molecule grabbing nonintegrin receptor-1 (SIGN-R1) and macrophage receptor with collagenous structure (MARCO), were decreased comparing with age-matched control case. Polymerase chain reaction (PCR) assay using each DNA, extraction from formalin-fixed paraffin-embedded specimen (FFPE) samples of lung, adrenal gland, heart, spleen, and kidney showed positive the ply gene and the lytA gene specific for Streptococcus pneumonia. Present case showed possible acquired atrophy of spleen, especially decreasing marginal zone macrophage may correlate with rapid progression of sepsis of Streptococcus pneumonia with massive adrenal hemorrhage. In addition, present case showed the usefulness of PCR using FFPE for the postmortem diagnosis of WFS. PMID- 26261664 TI - A SMARCB1-deficient vulvar neoplasm with prominent myxoid stroma: report of a case showing ERG and FLI1 expression. AB - In the vulvar region, epithelioid sarcoma (ES) is the most frequent SMARCB1 deficient neoplasm, followed by myoepithelial carcinoma (MC). Previous studies have demonstrated that some SMARCB1-deficient vulvar neoplasms cannot be classified as either ES or MC. Herein, we report of a 42-year-old woman with a SMARCB1-deficient neoplasm with prominent myxoid stroma in the vulva. It contained both epithelioid and spindled tumor cells, both of which showed vimentin and EMA expression. Although other markers useful for the differential diagnosis among SMARCB1-deficient tumors were negative, this tumor displayed characteristic expression of ERG and FLI1. As there are no reliable data regarding expression of ERG and FLI1 in MC, which are demonstrated to be often expressed in ES, further classification of cases such as the one reported here requires reliable data regarding their expression status in MC. PMID- 26261665 TI - Neoplastic lesions in CADASIL syndrome: report of an autopsied Japanese case. AB - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is one of the most common heritable causes of stroke and dementia in adults. The gene involved in the pathogenesis of CADASIL is Notch3; in which mutations affect the number of cysteine residues in its extracellular domain, causing its accumulation in small arteries and arterioles of the affected individuals. Besides the usual neurological and vascular findings that have been well-documented in CADASIL patients, this paper additionally reports multiple neoplastic lesions that were observed in an autopsy case of CADASIL patient; that could be related to Notch3 mutation. The patient was a 62 years old male, presented with a past history of neurological manifestations, including gait disturbance and frequent convulsive attacks. He was diagnosed as CADASIL syndrome with Notch3 Arg133Cys mutation. He eventually developed hemiplegia and died of systemic convulsions. Autopsy examination revealed-besides the vascular and neurological lesions characteristic of CADASIL- multiple neoplastic lesions in the body; carcinoid tumorlet and diffuse idiopathic pulmonary neuro-endocrine cell hyperplasia (DIPNECH) in the lungs, renal cell carcinoma (RCC), prostatic adenocarcinoma (ADC) and adenomatoid tumor of the epididymis. This report describes a spectrum of neoplastic lesions that were found in a case of CADASIL patient that could be related to Notch3 gene mutations. PMID- 26261666 TI - Richter transformation with c-MYC overexpression: report of three cases. AB - Pathogenesis of Richter transformation (RT) or Richter syndrome (RS) of chronic lymphocytic leukemia (CLL) is still largely unknown. Increasing evidences show that c-MYC may play a role in the development of RS. Here we report three cases of RS with overexpression of c-MYC. The first case was a 78-year-old male who initially presented with CLL and then developed diffuse lymphadenopathy and ascites shortly after. Ascites cytology showed a population of large lymphoid cells positive for MYC (8q24) rearrangement by fluorescence in situ hybridization (FISH) and overexpression of c-MYC by immunohistochemistry (IHC). The second case was a 66-year-old male presented with rapidly enlarging lymph nodes and pleural effusion after a long history of CLL. Biopsy showed large B-cells positive for c MYC overexpression and high Ki-67 proliferation index (80-90%). The third case was a 62-year-old female with CLL who presented for lobectomy for lung adenocarcinoma. Interestingly, along with the carcinoma, large B-cell lymphoma was incidentally found which had the same immunophenotype as the CLL. FISH analysis revealed gain of c-MYC at 8q and IHC showed increased c-MYC expression. This study supports that c-MYC plays a critical role in RS. PMID- 26261667 TI - Granulomatous inflammation of pulmonary squamous cell carcinoma: a rare phenomenon. AB - Some neoplasms are associated with granulomatous inflammation. Granuloma formation in tumor tissue is caused by the cytokines derived from either the main tumor or other cells surrounding the tumor. In other instances, granulomatous inflammation is observed in the lymph nodes draining a tumor. This has been recognized as a sarcoid-like reaction. Herein, we report of a 75-year-old man with pulmonary squamous cell carcinoma (SCC), where granulomatous inflammation was observed extensively at the primary site. The carcinoma seemed to partly regress. In the regressing area, tumor cell debris was surrounded by granuloma. In contrast, no granuloma was identified in the dissected regional lymph nodes. To the best of our knowledge, such a case of SCC had not been described thus far. More case studies are required to determine whether tumor-related granuloma is the main cause of regression or whether it is just a secondary phenomenon caused by the attack and destruction of the tumor by lymphocytes. PMID- 26261668 TI - Suprasellar hemangioblastoma without von Hippel-Lindau disease: a case report and literature review. AB - Suprasellar hemangioblastoma (HBL) without von Hippel-Lindau (VHL) disease is extremely rare. A 51-year-old woman presented with headache and progressively deteriorating bilateral visual disturbance for 4 months. Magnetic resonance imaging (MRI) revealed a 2.5-cm solid mass in the suprasellar region with homogeneous contrast enhancement. Our preoperative presumptive diagnosis was meningioma. Resection of the tumor was achieved via a left pterional craniotomy. The tumor was reddish in appearance and relatively firm, and was extremely vascularized, which might provide extensive blood supply through small branches of the internal carotid artery. There was a clear border between the tumor and the pituitary stalk and optic nerves. Histopathologic examination showed that the tumor was well vascularized, consisting of a reticular mesh of numerous thin walled capillaries and abundant stromal cells. Immunohistochemistry demonstrated the positive staining for CD34, vimentin (VIM), and neuron specific enolase (NSE) in the intratumoral capillaries, while negative staining of epithelial membrane antigen (EMA) and glial fibrillary acidic protein (GFAP) was observed. Based on these results, the patient was diagnosed as HBL. After the resection, the visual field defect in the left eye was markedly improved, and no tumor recurrence was noted in 1 year follow-up. When solid lesions are highly vascularized in the suprasellar region of patients, even though no VHL disease is present, the possibility of HBL should be taken into consideration. Moreover, craniotomy is a better treatment option for suprasellar HBL without VHL disease. PMID- 26261669 TI - Utility of immunohistochemistry with an antibody against MYC at the initial diagnosis of follicular lymphoma, grade 3A, for predicting a more aggressive clinical course: a case report and review of the literature. AB - Follicular lymphoma (FL) is the most common indolent lymphoma, and associated with the chromosomal translocation t(14;18)(q32;q21). While, FL harboring both BCL2 and MYC translocation at diagnosis is very rare. The evaluation of MYC expression in typical FL at presentation using southern blot, G-banded karyotyping or fluorescence in situ hybridization (FISH) analyses has been described so far. However, there are no reports about the use of immunohistochemistry (IHC) to evaluate MYC protein expression in FL at presentation. Here, we present a FL patient who transformed to a B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt's lymphoma, accompanied by concurrent BCL2, BCL6, and MYC translocations; i.e., triple-hit lymphoma. Paraffin-embedded tissue section-FISH analysis demonstrated that the FL was negative for MYC, but MYC protein expression was subsequently detected in the lymph node specimen obtained at the initial diagnosis using IHC. This case revealed aggressive clinical course and central nervous system involvement. In the literature concerning MYC positive FL five out of 8 patients were dead within 24 months. The detection of MYC protein expression in FL using IHC might be useful to predict more aggressive clinical course. PMID- 26261670 TI - Brunner's gland adenoma of duodenum: report of two cases. AB - Brunner's gland adenoma is a rare tumor of the duodenum and might also be an unusual cause of gastrointestinal bleeding or obstruction. The pathogenesis of Brunner gland hamartoma of the duodenum is unknown. We report two cases of Brunner's gland adenoma. Surgical resection was carried out because the tumor size was big in both cases and one accompanied with bleeding. Pathological examination revealed submucosal nodular hyperplasia of the Brunner's glands. PMID- 26261671 TI - Cerebellar pleomorphic xanthoastrocytoma in a patient with neurofibromatosis type 1: a case report and literature review. AB - Pleomorphic xanthoastrocytoma (PXA) is an uncommon tumor of young adults that typically occurs supratentorially. It is generally considered to be a low-grade, circumscribed tumor that when treated by surgical resection has a relatively favorable outcome. Cases of cerebellar PXA are rare, and those associated with neurofibromatosis type 1 (NF1) are even less common, with only 2 cases reported to date. We present herein a third case of PXA-NF1 with unusual features. A 33 year-old woman presented with a history of headache. Her medical and family history was significant for NF1. Brain MRI revealed a 3.4 cm ill-defined lesion with a gyriform enhancing pattern in the left cerebellum, superficially mimicking Lhermitte-Duclos disease. The patient underwent a gross total resection of the lesion and had an unremarkable postoperative course. While the lesion had histological features typical of "pure" PXA (WHO grade II) it had an unusual growth pattern with thickening of the superficial cerebellar folia and predominant leptomeningeal involvement. No BRAF, IDH-1, or IDH-2 mutation was identified. Three months after surgery, local recurrence was detected, and the patient was treated with radiation therapy. One year after the first surgery, she underwent surgical resection of the recurrent/residual tumor. Histologically, the recurrent tumor showed very similar features to the initially resected tumor, with no anaplastic features. Most cerebellar PXAs have an indolent clinical behavior as do most cerebral PXAs. Whether co-existence of NF1 was a factor in altering the clinical course and biologic behavior of this patient's tumor is currently unknown. PMID- 26261672 TI - Multiple primary Ewing's sarcomas in cerebral cranium of a child: a case report and review of the literature. AB - Ewing's sarcoma is the second most common pediatric bone tumor. Primary Ewing's sarcoma occurring in the cerebral cranium is exceptionally rare, with only one reported case of multiple tumor lesions in adolescence to date. We report a case of a 5-year-old male patient with multiple primary Ewing's sarcomas associated with the cranial bones, the first pediatric case report to date. We also review 71 cases Ewing's sarcoma involving intracranial extension. The purpose of this article is to provide data concerning the clinical and therapeutic course of multiple primary Ewing's sarcomas in associated with cerebral cranium. PMID- 26261673 TI - Similar MR imaging characteristics but different pathological changes: a misdiagnosis for Lhermitte-Duclos disease and review of the literature. AB - Although previous reports purpored that the unique magnetic resonance imaging (MRI) features of Lhermitte-Duclos disease (LDD) obviates the need for biopsy, we have made a misdiagnosis of LDD which has an indistinguishable imaging appearance. We present a patient who suffered from a normal cerebellum with arachnoid vascular malformation that had imaging characteristics which were indistinguishable from LDD before operation. This atypical imaging appearance, which could potentially be confused with LDD, may lead to misdiagnosis and inappropriate treatment in the absence of tissue sampling. Thus, this finding suggests that in those patients where images are highly suggestive of LDD but lack other manifestations of Cowden syndrome, biopsy is required and advanced imaging with magnetic resonance spectroscopy (MRS) should be strongly considered. PMID- 26261674 TI - Concurrent Epstein-Barr virus associated NK/T cell lymphoma after immunosuppressive therapy for aplastic anemia: report of a case and review of literature. AB - Aplastic anemia (AA) patients with prolonged immunosuppression have a risk of development of lymphoproliferative disorders (LPDs), especially combined with Epstein-Barr virus (EBV) infection. However, development of nature killer/T (NK/T) cell lymphoma, in a nontransplantation setting, has not been documented for AA patients with immunosuppressive therapy (IST). Herein, we described a middle-aged man, Han ethnic, who presented with swelled parotid gland after a long history of IST for AA. Fever, night sweating, weight loss had not been found. Increased heterotypic lymphocytes had been detected in the left side of parotid gland demonstrated as cCD3(+), CD56(+), GranB(+), TIA-1(+), MUM-1(+), KI 67 (50%-75%)(++), Bcl-6(-), MPO(-) by immunohistochemistry, and in-situ hybridization (ISH) indicated EBER positive. Chromosome analysis by R banding method revealed 46, XY [20]. NK/T cell lymphoma concurrent with aplastic anemia was diagnosed and a mild chemotherapy regimen including vincristine, prednisone, L-asparaginase was administered. The parotid mass was gradually regressed after the first cycle of chemotherapy. The patient discharged from the hospital voluntarily and lost the follow-up. PMID- 26261675 TI - Clear cell variant of diffuse large B-cell lymphoma: a case report and review of the literature. AB - Diffuse large B cell lymphoma (DLBCL) is a diffuse proliferation of large neoplastic B lymphoid cells with nuclear size equal to or exceeding that of normal macrophage nuclei. The DLBCL morphological variants are centroblastic, immunoblastic, T-cell- and histiocyte-rich, anaplastic, plasmablastic, anaplastic lymphoma kinase-positive, and primary mediastinal large B-cell lymphoma (PMBCL). These histopathologically-recognized morphological variants respond differently to treatment and have distinct prognoses. We report a case of a 43-year-old patient who presented pain in the lower abdomen that had begun four months prior. Ultrasound-guided biopsy revealed epithelial cell features and a partial alveolar growth pattern. We discovered large diffuse areas comprising large cells with slightly irregular nuclei and very clear cytoplasm. These features were similar to those of clear cell carcinoma in renal tissue, suggesting the possibility of an epithelial neoplasm. To test this possibility, immunohistochemistry for cluster designation markers was performed, but the diffuse areas were found to be positive only for CD45. Additional immunohistochemistry was performed, and the diffuse areas were found to be positive for CD20, CD79a, P53, and Mum-1. Based on these characteristics, a diagnosis of a clear cell variant of DLBCL was made, and the patient was treated with chemotherapy. Precise histological diagnosis is crucial for clinical management and ultimately for patient survival. There has been one additional report of a case of clear cell DLBCL, in outside the mediastinum. The features we identified can be used to define a new subtype of DLBCL. The expression of P53 and Mum-1 suggest a poor prognosis. PMID- 26261676 TI - Well-differentiated mucinous uterine adenocarcinoma predominantly diagnosed as adenoma malignum: a case report with an immunohistochemical analysis. AB - Adenoma malignum (AM), also referred to as "minimal deviation adenocarcinoma", is an extremely uncommon variant of highly-differentiated adenocarcinoma of the uterine cervix. The study presented herein describes a case of uterine AM found out after hysteroscopy. An early-stage, well-differentiated mucinous uterine adenocarcinoma was diagnosed post-operatively. A subsequent immunohistochemical assessment of a panel of antibodies was applied, in order to distinguish between female genital tract malignancies. PMID- 26261677 TI - Myxoid dermatofibroma on a great toe: a case report. AB - Dermatofibroma is a common benign fibrohistiocytic tumor with many clinicopathological variants. Myxoid dermatofibroma is one of these variants, which is characterized by marked stromal mucin deposition. This report presents a case of myxoid dermatofibroma on a great toe that had been slowly growing for two years. Histopathologically, the relatively well-circumscribed dermal tumor was separated from the epidermis by a small grenz zone. The tumor tissue consisted of oval to spindle-shaped cells with well-defined cell borders and spindly condensed nuclei. No cytologic atypia or mitotic figures were found. Although most of the tumor cells were embedded in a prominently myxoid stroma, typical features of classic dermatofibroma including a storiform growth pattern and more densely packed collagen were observed at the periphery. Immunohistochemically, the tumor cells showed positive staining for CD68 and CD99, and negative staining for CD34 and S-100. Histopathological differential diagnoses of myxoid dermatofibroma include soft tissue neoplasms with myxoid tumor stroma, such as superficial acral fibromyxoma, cellular digital fibroma, superficial angiomyxoma, myxoid dermatofibrosarcoma protuberans and low-grade fibromyxoid sarcoma. Immunohistochemical staining can be useful in the differential diagnosis of these tumors. This case highlights the challenges encountered in the histopathological interpretation of myxoid dermatofibroma. Pathologists should keep in mind the diagnosis of myxoid dermatofibroma when dealing with myxoid neoplastic lesions arising on acral sites. PMID- 26261678 TI - Endometrial tubal metaplasia in a young puerperal woman after breast cancer. AB - INTRODUCTION: Tamoxifen is the usual endocrine (anti-estrogen) therapy for hormone receptor-positive breast cancer in pre and post-menopausal women. Previous studies have suggested an increased prevalence of endometrial diseases after treatment with tamoxifen. CASE PRESENTATION: The authors report a case of 38-year-old woman with diagnosis of endometrial polyp and tubal metaplasia, during puerperium and after micropapillary ductal breast cancer surgery, 5 years of tamoxifen treatment, spontaneous pregnancy without complications and full-term vaginal delivery. CONCLUSION: Tamoxifen is a safe and reliable treatment of breast cancer, but data suggest an association with endometrial polyps, hyperplasia, metaplasia and carcinoma. One of the most common types of endometrial metaplasia is ciliated tubal metaplasia. It is generally known that endometrial tubal metaplasia is a benign disease. However studies propose endometrial tubal metaplasia to be a potential premalignant endometrial lesion and its association with endometrial hyperplasia and well-differentiated endometrioid carcinoma. We propose close monitoring of patients taking tamoxifen and prompt evaluation of any uterine bleeding or pelvic complaint or abnormal TVUS images. PMID- 26261679 TI - Guillain-Barre syndrome: report of two rare clinical cases occurring after allergenic bone grafting in oral maxillofacial surgery. AB - Guillaine-Barre Syndrome (GBS), also known as post-infectious polyneuropathy or acute idiopathic polyneuritis, is an infrequent disorder of the peripheral nervous system. The cause of GBS is unknown. It has been associated in the past with microbial infections, vaccinations, surgical procedures and debilitation of the patient. The classic signs of GBS occurring in the two patients being reported here are muscle weakness, motor and sensory impairment and ascending paralysis with respiratory involvement. The documented cases involved GBS syndrome following oral and maxillofacial surgery in which allogeneic-banked freeze-dried bone have been utilized along with autogenous grafting. There were no incidents of viral infection, vaccination or the other prodromal incidents involved in these cases. It is believed that the description of these two cases would be of interest in that it may stimulate the reporting of similar anecdotal occurrences by other surgeons. Both patients fully recovered from the GBS and are presently alive and well. PMID- 26261680 TI - Comments on Bu et al. "P16(INK4a) overexpression and survival in osteosarcoma patients: a meta analysis". AB - Recently, we read the article "P16(INK4a) overexpression and survival in osteosarcoma patients: a meta analysis" by Jie Bu and his colleagues, published in the recent issue of International Journal Of Experimental Pathology. This research performed a meta-analysis to uncover the role of P16(INK4a) expression in overall survival rate in patients with osteosarcoma. The investigators concluded as follows: (i) the pateints with overexpression of P16(INK4a) had a longer overall survival rate than that with loss expression of P16(INK4a); (ii) P16(INK4a) was an effective biomarker of prognosis in patients with osteosarcoma.The findings are valubale and encouraging. However, some flaws and imperfections rooted in this work. PMID- 26261681 TI - Primary pulmonary adenoid cystic carcinoma: clinicopathological analyses of 12 cases. AB - BACKGROUND AND OBJECTIVES: Adenoid cystic primary pulmonary carcinomas (adenoid cystic carcinomas or ACCs) are rare tumors, so we described the clinical and pathological features of these tumors and related these findings with diagnosis and prognosis of ACC, comparing our data to the existing literature. METHODS: Clinical and pathological features of 12 ACC cases were observed and described. Immunohistochemical EnVision staining, fluorescent PCR detection, and FISH were used to characterize tumor samples and the literature was reviewed. RESULTS: Of the 12 ACC cases (7 male; average 53.1 years-of-age; range 33-78 years), the chief presentation symptom was cough, followed by expectoration, gasping, and bloody sputum. Microscopically, histopathology revealed cribriform, tubular, or solid cords. CD117 was overexpressed in glandular epithelia in 9 cases and calcitonin and thyroid transcription factor-1 (TTF-1) were overexpressed in 4 cases. One case was positive for EML4 ALK gene rearrangement. CONCLUSION: ACC is a low-grade malignant tumor with poor prognosis and high recurrence and metastases. TTF-1 expression indicates a primary tumor and CD117 expression is not significant to prognosis. PMID- 26261682 TI - Coexistence of multiple myeloma and clear cell renal cell carcinoma: a case report and review of literature. AB - Coexistence of multiple myeloma (MM) and renal cell carcinoma (RCC) is an extremely rare condition. Nevertheless, there is a higher than expected incidence of co-occurrence of these two malignancies. Several case series, in the recent past, have postulated an association between MM and RCC. Population-based data analyses have revealed a bi-directional association between these two malignancies. However, the cause still remains speculative up to date. Here, we aim to describe a patient with MM and clear cell renal cell carcinoma (CCRCC) one after another for the second time from China. Clinical implications are discussed with a critical review of existing literature and we expect to draw much more awareness among clinicians regarding such association. PMID- 26261683 TI - Cross-talk between TGF-beta/Smad pathway and Wnt/beta-catenin pathway in pathological scar formation. AB - TGF-beta1 is a key factor in the process of wound healing, which is regulated by TGF-beta/Smad pathway. We previously demonstrated that TGF-beta1 contributed to pathological scar formation. And previous studies also suggested Wnt/beta-catenin pathway might be involved in wound healing. However, their role and relation in pathological scar formation remains not very clear. For evaluating TGF-beta1 and beta-catenin, key factors of the two signal pathways, immunohistochemistry, western blot analysis and RT-PCR were used. Simultaneously, immunohistochemistry were used to evaluate Smad2, Smad3 and Wnt-1, which were also the important factors. We found that they all significantly accumulated in pathological scars compared with normal skins (P<0.05), that implied the two signal pathways both contributed to pathological scar formation. Meanwhile, beta-catenin expression showed a tendency to increase first and then decrease under the influence of different concentrations of TGF-beta1 (P<0.01). It is possible that there is a complicated interaction between the two signal pathways in pathological scar formation (both synergy and antagonism). PMID- 26261684 TI - Inhibitory effect of chloroquine derivatives on presenilin 1 and ubiquilin 1 expression in Alzheimer's disease. AB - Alzheimer's disease is the common cause of dementia characterized by the accumulation of amyloid-beta produced by breakage of amyloid-beta precursor protein (APP). The present study was designed to synthesize and investigate the effect of chloroquine derivatives on the expression of presenilin. Among the five chloroquine derivatives (D1, D2, D3, D4 and D5) synthesized, D5 with diisopropyl substitution was found to be most effect. The results from western blot analysis showed the inhibition of presenilin 1 protein expression on treatment with chloroquine derivative D5 in Daudi cells. The results were also confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR). It was observed that chloroquine derivative D5 downregulates presenilin expression via the inhibition of ubiquilin 1 expression. Thus our study demonstrates that chloroquine derivative D5 treatment can have preventive against Alzheimer's disease. PMID- 26261685 TI - Expression of SIRT1 and oxidative stress in diabetic dry eye. AB - OBJECTIVE: To explore the expression of SIRT1 with oxidative stress and observe physiological and pathological changes in the corneas as well as the association between SIRT1 and oxidative stress of diabetic dry eyes in mice. METHOD: Forty eight C57BL/6Jdb/db mice at eight weeks of age were divided randomly into two groups: the diabetic dry eye group and the diabetic group. An additional forty eight C57BL/6J mice at eight weeks of age were divided randomly into two groups: the dry eye group and the control group. Every mouse in the dry eye groups (diabetic and normal) was injected with scopolamine hydrobromide three times daily, combined with low humidity to establish a dry eye model. After the intervention, phenol red cotton string tests and corneal fluorescein staining were performed. In addition, HE staining and immunofluorescence were done. Expression of SIRT1 in the cornea was examined by real-time PCR and Western Blot and expression of FOXO3 and MnSOD proteins was detected by Western Blot. RESULTS: At one, four, and eight weeks post intervention, all of the groups except the controls showed significant decreases in tear production and increases in the corneal fluorescein stain (P<0.05 vs control). Between the experimental groups, the diabetic dry eye group had the least tear production and the highest corneal fluorescein stain score (P<0.05). As the disease progressed, all of the experimental groups showed obviously pathological changes in HE staining, particularly the diabetic dry eye group. In the 1(st) and 4(th) week, the expression of SIRT1, FOXO3, and MnSOD were significantly higher in the diabetic DE and DM groups but lower in the DE group compared to the controls (P<0.05). In the 8(th) week, the expression of SIRT1, FOXO3, and MnSOD was significantly down regulated in the diabetic DE group and the DM group (P<0.05). Immunofluorescence showed similar results. CONCLUSION: In the condition of diabetic dry eye, tear production declined markedly coupled with seriously wounded corneal epithelium. Oxidative stress in the cornea was enhanced significantly and the expression of SIRT1 was decreased. PMID- 26261686 TI - Long non-coding RNAs era in liver cancer. AB - Hepatocellular carcinoma (HCC) is one of the most common malignancies leading to high mortality rates in the general population and the sixth most common cancer worldwide. HCC is characterized by deregulation of multiple genes and signalling pathways. These genetic effects can involve both protein coding genes as well as non-coding RNA genes. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nt, constituting a subpopulation of ncRNAs. Their biological effects are not well understood compared to small non-coding RNA (microRNAs), but they have been recently recognized to exert a crucial role in the regulation of gene expression and modulation of signalling pathways. Notably, several studies indicated that lncRNAs contribute to the pathogenesis and progression of HCC. Investigating the molecular mechanisms underlying lncRNAs expression opens potential applications in diagnosis and treatment of liver disease. This editorial provides three examples (MALAT-1 metastasis associated lung adenocarcinoma transcript, HULC highly upregulated in liver cancer and HOTAIR HOX transcript antisense intergenic RNA) of well-known lncRNAs upregulated in HCC, whose mechanisms of action are known, and for which therapeutic applications are delineated. Targeting of lncRNAs using several approaches (siRNA-mediated silencing or changing their secondary structure) offers new possibility to treat HCC. PMID- 26261687 TI - Role of systemic inflammation in cirrhosis: From pathogenesis to prognosis. AB - The natural history of cirrhosis can be divided into an initial stage, known as compensated cirrhosis, and an advanced stage which encompasses both decompensated cirrhosis and acute-on-chronic liver failure (ACLF). The latter syndrome has been recently described as an acute deterioration of liver function in patients with cirrhosis, which is usually triggered by a precipitating event and results in the failure of one or more organs and high short-term mortality rates. Each stage is characterized by distinctive clinical manifestations and prognoses. One of the key elements involved in cirrhosis physiopathology is systemic inflammation, recently described as one of the components in the cirrhosis-associated immune dysfunction syndrome. This syndrome refers to the combination of immune deficiency and exacerbated inflammation that coexist during the course of cirrhosis and relates to the appearance of clinical complications. Since systemic inflammation is often difficult to assess in cirrhosis patients, new objective, reproducible and readily-available markers are needed in order to optimize prognosis and lengthen survival. Thus, surrogate serum markers and clinical parameters of systemic inflammation have been sought to improve disease follow-up and management, especially in decompensated cirrhosis and ACLF. Leukocyte counts (evaluated as total leukocytes, total eosinophils or neutrophil:lymphocyte ratio) and plasma levels of procalcitonin or C-reactive protein have been proposed as prognostic markers, each with advantages and shortcomings. Research and prospective randomized studies that validate these and other markers are clearly warranted. PMID- 26261688 TI - Autophagy: A new therapeutic target for liver fibrosis. AB - Hepatic fibrosis is a wound-healing response to liver injury and the result of imbalance of extracellular matrix (ECM) accumulation and degradation. The relentless production and progressive accumulation of ECM can lead to end-stage liver disease. Although significant progress has been achieved in elucidating the mechanisms of fibrogenesis, effective anti-fibrotic strategies are still lacking. Autophagy is an intracellular process of self-digestion of defective organelles to provide material recycling or energy for cell survival. Autophagy has been implicated in the pathophysiology of many human disorders including hepatic fibrosis. However, the exact relationships between autophagy and hepatic fibrosis are not totally clear and need further investigations. A new therapeutic target for liver fibrosis could be developed with a better understanding of autophagy. PMID- 26261689 TI - Focal liver lesions: Practical magnetic resonance imaging approach. AB - With the widespread of cross-sectional imaging, a growth of incidentally detected focal liver lesions (FLL) has been observed. A reliable detection and characterization of FLL is critical for optimal patient management. Maximizing accuracy of imaging in the context of FLL is paramount in avoiding unnecessary biopsies, which may result in post-procedural complications. A tremendous development of new imaging techniques has taken place during these last years. Nowadays, Magnetic resonance imaging (MRI) plays a key role in management of liver lesions, using a radiation-free technique and a safe contrast agent profile. MRI plays a key role in the non-invasive correct characterization of FLL. MRI is capable of providing comprehensive and highly accurate diagnostic information, with the additional advantage of lack of harmful ionizing radiation. These properties make MRI the mainstay for the noninvasive evaluation of focal liver lesions. In this paper we review the state-of-the-art MRI liver protocol, briefly discussing different sequence types, the unique characteristics of imaging non-cooperative patients and discuss the role of hepatocyte-specific contrast agents. A review of the imaging features of the most common benign and malignant FLL is presented, supplemented by a schematic representation of a simplistic practical approach on MRI. PMID- 26261690 TI - Transarterial chemoembolization: Evidences from the literature and applications in hepatocellular carcinoma patients. AB - Transarterial chemoembolization (TACE) is the current standard of care for patients with large or multinodular hepatocellular carcinoma (HCC), preserved liver function, absence of cancer-related symptoms and no evidence of vascular invasion or extrahepatic spread (i.e., those classified as intermediate stage according to the Barcelona Clinic Liver Cancer staging system). The rationale for TACE is that the intra-arterial injection of a chemotherapeutic drug such as doxorubicin or cisplatin followed by embolization of the blood vessel will result in a strong cytotoxic effect enhanced by ischemia. However, TACE is a very heterogeneous operative technique and varies in terms of chemotherapeutic agents, treatment devices and schedule. In order to overcome the major drawbacks of conventional TACE (cTACE), non-resorbable drug-eluting beads (DEBs) loaded with cytotoxic drugs have been developed. DEBs are able to slowly release the drug upon injection and increase the intensity and duration of ischemia while enhancing the drug delivery to the tumor. Unfortunately, despite the theoretical advantages of this new device and the promising results of the pivotal studies, definitive data in favor of its superiority over cTACE are still lacking. The recommendation for TACE as the standard-of-care for intermediate-stage HCC is based on the demonstration of improved survival compared with best supportive care or suboptimal therapies in a meta-analysis of six randomized controlled trials, but other therapeutic options (namely, surgery and radioembolization) proved competitive in selected subsets of intermediate HCC patients. Other potential fields of application of TACE in hepato-oncology are the pre-transplant setting (as downstaging/bridging treatment) and the early stage (in patients unsuitable to curative therapy). The potential of TACE in selected advanced patients with segmental portal vein thrombosis and preserved liver function deserves further reports. PMID- 26261691 TI - Biological features and biomarkers in hepatocellular carcinoma. AB - Similar to other cancers, a multistep process of carcinogenesis is observed in hepatocellular carcinoma (HCC). Although the mechanisms underlying the development of HCC have been investigated in terms of oncology, virology, and stem cell biology, the whole picture of hepatocarcinogenesis remains to be elucidated. Recent progress in molecular biology has provided clues to the underlying cause of various diseases. In particular, sequencing technologies, such as whole genome and exome sequencing analyses, have made an impact on genomic research on a variety of cancers including HCC. Comprehensive genomic analyses have detected numerous abnormal genetic alterations, such as mutations and copy number alterations. Based on these findings, signaling pathways and cancer-related genes involved in hepatocarcinogenesis could be analyzed in detail. Simultaneously, a number of novel biomarkers, both from tissue and blood samples, have been recently reported. These biomarkers have been successfully applied to early diagnosis and prognostic prediction of patients with HCC. In this review, we focus on the recent developments in molecular cancer research on HCC and explain the biological features and novel biomarkers. PMID- 26261692 TI - Optimal combination of antiangiogenic therapy for hepatocellular carcinoma. AB - The success of sorafenib in prolonging survival of patients with hepatocellular carcinoma (HCC) makes therapeutic inhibition of angiogenesis a component of treatment for HCC. To enhance therapeutic efficacy, overcome drug resistance and reduce toxicity, combination of antiangiogenic agents with chemotherapy, radiotherapy or other targeted agents were evaluated. Nevertheless, the use of antiangiogenic therapy remains suboptimal regarding dosage, schedule and duration of therapy. The issue is further complicated by combination antiangiogenesis to other cytotoxic or biologic agents. There is no way to determine which patients are most likely respond to a given form of antiangiogenic therapy. Activation of alternative pathways associated with disease progression in patients undergoing antiangiogenic therapy has also been recognized. There is increasing importance in identifying, validating and standardizing potential response biomarkers for antiangiogenesis therapy for HCC patients. In this review, biomarkers for antiangiogenesis therapy including systemic, circulating, tissue and imaging ones are summarized. The strength and deficit of circulating and imaging biomarkers were further demonstrated by a series of studies in HCC patients receiving radiotherapy with or without thalidomide. PMID- 26261693 TI - Physical activity as a treatment of non-alcoholic fatty liver disease: A systematic review. AB - AIM: To review the effectiveness of exercise as a therapy for nonalcoholic fatty liver disease (NAFLD) and potential benefits in treating insulin resistance and atherosclerosis. METHODS: Medline (EBSCOhost) and PubMed were searched for English-language randomized controlled trials and prospective cohort studies in human adults aged >= 18 which investigated the various effects of exercise alone, a combination of exercise and diet, or exercise and diet coupled with behavioral modification on NAFLD from 2010 to Feburary 2015. RESULTS: Eighteen of 2298 available studies were chosen for critical review, which included 6925 patients. Nine (50%) studies were randomized controlled trials. Five (27.8%) studies utilized biopsy to examine the effects of physical activity on hepatic histology. The most commonly employed imaging modality to determine change in hepatic steatosis was hydrogen-magnetic resonance spectroscopy. Only two studies examined the effects of low impact physical activity for patients with significant mobility limitations and one compared the efficacy of aerobic and resistance exercise. No studies examined the exact duration of exercise required for hepatic and metabolic improvement in NAFLD. CONCLUSION: While exercise improved hepatic steatosis and underlying metabolic abnormalities in NAFLD, more studies are needed to define the most beneficial form and duration of exercise treatment. PMID- 26261694 TI - The comparison of plasma D-dimer levels in benign and malignant tumors of cervix, ovary and uterus. AB - BACKGROUND: Thromboembolism is the most important complication of cancers.The aim of this study was to determine D-dimer levels in benign and malignant tumors of the uterus, ovary and cervix. SUBJECTS AND METHODS: This was a cross sectional study and it was conducted on 90 female patients referred to Imam Khomeini and Arash Hospitals because of uterine, cervical and ovarian tumors in 2013-2014. After surgical resection or tissue biopsy, 2 cc of each patient's blood was taken to be sent to laboratory of hospitals. "Nycocard" kit was chosen to measure D dimer levels in Mg/Lit by neflumetry method. Data were analyzed in SPSS-16 by T test and One-Way ANOVA test. RESULTS: The highest mean of D-dimer was 3.9 (+/- 2.9SD) in malignant cervical tumors. The mean plasma levels of D-dimer in malignant uterine cancers (P = 0.008), ovarian cancers (P = 0.007) and cervical cancers (P = 0.006) was significantly higher than benign tumors. In all three types of uterine, ovarian and cervical cancers, D-dimer was significantly higher in advanced stages than lower stages. CONCLUSION: The plasma D-dimer levels in patients with malignant tumors of the uterus, cervix and ovary were higher than benign types. By increasing the stage of gynecologic malignant tumors, the levels of plasma D-dimer were increased. PMID- 26261695 TI - Effects of aGVHD and cGVHD on Survival Rate in Patients with Acute Myeloid Leukemia after Allogeneic Stem Cell Transplantation. AB - BACKGROUND: Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is a curative treatment option for many patients with Acute Myeloid Leukemia (AML); however, it can lead to complications of Graft-Versus-Host-Disease (GVHD) which can affect the quality of life and overall survival. The aim of this study was to assess the effects of both acute and chronic GVHD on survival rate in patients with AML who received HSCT. SUBJECTS AND METHODS: In a longitudinal study, 587 patients with AML who underwent bone marrow transplantation in Tehran-Iran between1991 and 2011 were recruited. All patient records were analyzed for the occurrence of adverse events including acute and chronic GVHD and leukemia relapse. Data were analyzed using Log-rank, Kaplan-Meier, Univariate and Multivariate Cox Regression models. RESULTS: The five-year overall survival (OS) was found to be 71.9% (95% CI: 67.40-76.41). Also there was a significant relationship between cGVHD and OS (P=0.001, HR = 0.476, 95%). Hazard of death in these patients was less than those who did not experience an occurrence of cGVHD and aGVHD (HR= 0.629, P= 0.078). A significant relationship between cGVHD and relapse was observed (P< 0.001) indicating that patients who developed cGVHD experienced a better survival rate. A significant relationship was also found between overall survival and aGVHD grade (P< 0.001). Hazard of death (HD) for cGVHD and relapse variables were estimated to be 0.554 and 3.869. DISCUSSION: This study is one of the largest studies (regarding the number of participants) done to date in the Middle East with quite a long duration (20 years). cGVHD appears to have a positive influence on survival rate in patients with AML who received HSCT. It is recommended that further studies investigate the underlying reason or mechanisms behind this. PMID- 26261696 TI - Overall Quality of Life Assessment in the Patients Undergoing External Beam Radiation in Outpatient Radiation Oncology Department. AB - BACKGROUND: The impact of treatment on cancer patients' quality of life (QoL) has been the focus of a variety of longitudinal studies in English literature for past decade. The measurement of patient-reported outcomes which includes health related quality of life is a new important initiative which has emerged and grown over the past three decades. Following the development of reliable and valid self reported questionnaires, health-related quality of life has been assessed in tens of thousands of patients and a wide variety of cancers. With growing information, feedback and experience, the quality of the health-related QOL studies has improved a lot. We expect in near future more methodologically robust studies will be done in a scientific way to answer unanswered questions. METHODS: As part of a Dean's summer project, a survey was undertaken to facilitate a more complete description of the quality of life experience in patients with histological diagnosis of cancer undergoing external beam radiation as an outpatient at Allan Blair Cancer Center, Regina, Canada. The questionnaires had two major components: depression and global QOL. The depression was measured by the Zung Self-Rating Depression Scale which is a short self-administered survey to quantify the depression status of a patient. RESULTS: Overall, only the equation associated with the outcome of QoL - Physical well-being was significant. That data indicated that only the variable of age was a significant predictor. A positive relationship was present indicating higher levels of depression when patients received chemotherapy or narcotics. Breast cancer patients were less depressed than lung cancer patients. CONCLUSION: Cancer and its related treatment is an important health issue influencing QoL. The study has revealed that the use of chemotherapy and narcotics has a significant impact on the quality of life (QoL). PMID- 26261697 TI - Prevalence of Iron deficiency anemia in children with liver cirrhosis: A cross sectional study. AB - BACKGROUND: Among the many complications reported for cirrhosis, iron deficiency anemia (IDA) has attracted much attention. This type of anemia, in contrast to other types of anemia, is easy to treat prophylactically, but if left untreated can lead to a poor quality of life. The aim of this study was to estimate the hemoglobin and serum iron levels among patients with liver cirrhosis for the early diagnosis of IDA and to avoid unnecessary testing and iron supplementation. SUBJECTS AND METHODS: In this cross-sectional study, 88 children diagnosed with cirrhosis were included, and the values of hemoglobin, serum iron levels and relationship between serum iron (SI), total iron-binding capacity (TIBC), prothrombine time (PT), international normalization ratio (INR), total and direct bilirubin and hepatic enzymes were estimated using paired t test, Mann-Whitney, Chi-square and Kruskal-Wallis tests. RESULTS: Forty-six (52.3%) of 88 children were girls and 42 (47.7%) were boys. Forty-eight (54.5%) patients had anemia and 8 (9%) had iron deficiency anemia (5 boys, 5.6%, and 3 girls, 3.4%). No relationships were observed between iron deficiency anemia and the patient's age or gender, whereas there was a relationship between iron deficiency and severity and duration of the disease, although the correlation was not statistically significant. CONCLUSION: The high frequency of iron deficiency anemia in children with cirrhosis (9%) suggests that timely screening should be used for early diagnosis and treatment. PMID- 26261698 TI - Hairy cell leukemia: A retrospective study on 11 patients in the Western of Iran. AB - BACKGROUND: Hairy cell leukemia (HCL) is a chronic B-cell lymphoid leukemia characterized by pancytopenia, splenomegaly, myelofibrosis and the presence in peripheral blood, bone marrow and spleen of atypical lymphoid cells with a hairy aspect. The study aims to evaluate a group of patients with hairy cell leukemia, hospitalized in the Clinic of Hematology and Oncology, Kermanshah, Iran, on a period of 15 years and affect of between cladribine therapy and IFN therapy on the patients with HCL. METHODS: This is a retrospective analysis of 11 patients in the Clinic of Hematology and Oncology, Kermanshah, Iran, between 2004 and 2013. Clinical features at diagnosis, differential count (platelet, Hb and WBC) types of therapy, survival rate and BRAF mutation have been monitored. As a result, cladribine therapy is the best treatment option for patients. RESULTS: The mean age of patients was 50 years with 100% of men. Approximately 45% of them had splenomegaly at diagnosis. 100% of patients had pancytopenia at diagnosis.9% of patients had mutation of BRAF V600E. Before of treatment, there were fatigue, weight loss, vomiting, fever, night sweat and itching in all of the patients. CONCLUSION: There is presence of hairy cells in peripheral blood and bone marrow and was associated with pancytopenia, splenomegaly, myelofibrosis in HCL patients. Also, cladribine therapy is best option for treatment of patients and it is better than IFN. PMID- 26261699 TI - Spectrum of alpha-globin gene mutations among premarital Baluch couples in southeastern Iran. AB - BACKGROUND: Alpha thalassemia (alpha-thal) is one of the most common hemoglobinopathies worldwide. The aim of this study was to investigate the spectrum of alpha-thal mutations among premarital Baluch couples in southeastern Iran. SUBJECTS AND METHODS: We assessed 1215 individuals by multiplex gap polymerase chain reaction (gap-PCR) and amplification refractory mutation system (ARMS-PCR). RESULTS: Of the 1215 participants with mean age of 23+/-5.7 years, 62.3% lived in urban areas, and the rate of consanguineous marriage was 68.1%. Five mutations were identified, the most frequent one was -alpha (3.7) (rightward) with a frequency of 76.5%, followed by alpha (-5 nt) (16.8%), alpha2/ Codon 19(-G) (4%), -alpha (4.2) (leftward)(2.4%), - -MED (0.3%) among mutated alleles of the alpha -globin gene. Conclusion : Knowing the alpha-genotype is helpful for genetic counseling, microcytic anemia discrimination and hemoglobinopathy prevention. PMID- 26261701 TI - Cold Autoimmune Hemolytic Anemia due to High-grade non Hodgkin's B cell Lymphoma with Weak Response to Rituximab and Chemotherapy Regimens. AB - Autoimmune hemolytic anemia (AIHA) is characterized by shortening of red blood cell (RBC) survival and the presence of autoantibodies directed against autologous RBCs. Approximately 20% of autoimmune hemolytic anemia cases are associated with cold-reactive antibody. About half of patients with AIHA have no underlying associated disease; these cases are termed primary or idiopathic. Secondary cases are associated with underlying diseases or with certain drugs. We report herein a rare case of cold autoimmiune hemolytic anemia due to high-grade non-Hodgkin's lymphoma of B-cell type with weak response to rituximab and chemotherapy regimens. For treatment B cell lymphoma, Due to lack of treatment response, we used chemotherapy regimens including R- CHOP for the first time, and then Hyper CVAD, R- ICE and ESHAP were administered, respectively. For treatment of autoimmune hemolytic anemia, we have used the corticosteroid, rituximab, plasmapheresis and blood transfusion and splenectomy. In spite of all attempts, the patient died of anemia and aggressive lymphoma nine months after diagnosis. To our knowledge, this is a rare report from cold autoimmune hemolytic anemia in combination with high-grade non-Hodgkin's lymphoma of B-cell type that is refractory to conventional therapies. PMID- 26261700 TI - The Newly Identified T Helper 22 Cells Lodge in Leukemia. AB - Leukemia is a hematological tumor in which the malignant myeloid or lymphoid subsets play a pivotal role. Newly identified T helper cell 22 (Th22) is a subset of CD4(+) T cells with distinguished gene expression, function and specific properties apart from other known CD4(+) T cell subsets.Th22 cells are characterized by production of a distinct profile of effector cytokines, including interleukin (IL)-22, IL-13, and tumor necrosis factor-alpha (TNF alpha). The levels of Th22 and cytokine IL-22 are increased and positively related to inflammatory and autoimmune disorders. Recently, several studies have reported the changes in frequency and function of Th22 in acute leukemic disorders as AML and ALL. This review discusses the role of Th22 and its cytokine IL-22 in the immunopathogenesis of leukemic disease. PMID- 26261702 TI - Follicular Dendritic Cell Sarcoma of Lymph Node: A report of a Patient with Chronic Myeloid Leukemia Treated with Imatinib. AB - Follicular dendritic cells or dendritic reticulum cells are important components of the immune system essential for antigen presentation. Malignancies arising from these cells are uncommon and the first case was reported in 1986. The most common sites of follicular dendritic cell sarcomas are lymph nodes, especially cervical, axillary and mediastinal regions, but extranodal sites including head and neck and gastrointestinal tract may be affected in one-third of patients. Immunohistochemistry plays an important role in its diagnosis to differentiate it from morphologically similar malignancies The present report describes a case of follicular dendritic cell sarcoma in a patient with chronic myeloid leukemia (CML) treated with imatininb mesylate for 6 years. This case deserves reporting due to rarity of the disease and hitherto unreported association with CML. Furthermore, the pathological diagnosis is challenging and requires a close-knit effort between the pathologist and haematologist. PMID- 26261703 TI - Conceptualization of the dynamics and synergistic partnership between the agri food production chain and public health veterinarians. PMID- 26261704 TI - Comparing protective effect of grape seed extract versus atorvastatin on endometriosis in rat model: Evidence for immunohistochemical and biochemical alterations. AB - Thirty six Wistar albino rats with implant induced endometriosis were randomly divided into six groups of six animals each. The rats in the first group received nothing and were euthanized at day 21. In the second group, rats received nothing and were euthanized at day 36. The third group received atorvastatin (ATV; 5 mg kg(-1) per day, orally) until 21 days from induction of endometriosis, and the fourth group received ATV from the 15(th) day after induction of endometriosis for 21 days. The fifth group received grape seed extract (GET; 450 mg kg(-1) per day, orally) until 21 days from induction of endometriosis. In the sixth group, GET was administered from the 15(th) day after induction of endometriosis for 21 days. The estrogen receptor positive cells (ER+) distribution and angiogenesis were assessed using immunohistochemical and immunoflourescent analyzes, respectively. The active cells with intracytoplasmic carbohydrate content were analyzed. Eralpha mRNA expression was assessed using semiquantitative real time PCR and the tissue levels of malondialdehyde (MDA), glutathione peroxidase (GSH px) and superoxide dismutase (SOD) were evaluated. The GET and ATV-treated animals showed significant reduction in endometriosis-increased ER+ cells distribution as well as significant decrease in Eralpha mRNA levels (p < 0.05(. Our data suggests that GET exerts a potent inhibitory effect on development of endometriotic implants similar to ATV. PMID- 26261705 TI - Effects of electron beam, NaOH and urea on chemical composition, phenolic compounds, in situ ruminal degradability and in vitro gas production kinetics of pistachio by-products. AB - The current study evaluated the effects of electron beam (EB; 10, 20, 30 and 40 kGy), urea and NaOH treatments on chemical composition, phenolic compounds, in vitro gas production and i n situ ruminal degradability of pistachio by-product (PB). The EB decreased (p < 0.01) neutral detergent fiber (NDF), acid detergent fiber (ADF) and acid detergent lignin (ADL) contents of PB. Treating PB by NaOH and urea increased cell wall constitute of PB (p < 0.01). Irradiation at doses of 30 and 40 kGy reduced tannin and increased total phenol content of PB (p < 0.01). NaOH and urea treatments decreased tannins, total phenolics and condensed tannins of PB compared to control (p < 0.01). In situ ruminal dry matter (DM) degradation data showed that irradiation increased (p < 0.01) and, urea and NaOH decreased (p < 0.01) rapidly fermentable fraction (a) of PB. NaOH decreased (p < 0.01) fraction b and total degradable fraction (a + b) of PB. Irradiation and polyethylene-glycol increased rate of gas production (k), metabolizable energy (ME) and short chain fatty acid concentrations (SCFA), while, NaOH decreased gas production potential (b), ME and SCFA (p < 0.01). Data showed that although NaOH was efficient in detannification of PB, however, it reduced gas production and in situ degradation of PB. PMID- 26261706 TI - Protective role of grape seed proanthocyanidin antioxidant properties on heart of streptozotocin-induced diabetic rats. AB - Grape seed proanthocyanidin (GSP) bears a very powerful antioxidant effects. Studies demonstrated that proanthocyanidins protect against free radicals mediated cardiovascular and renal disorders. The present study was designed to assess the effect of GSP on the heart of diabetic rats. Forty rats were divided into four groups of 10 animals each: Group I: control, Group II: control group were given GSP, Group III: diabetic group, Group IV: diabetic group treated with GSP. Diabetes was induced by a single dose of streptozotocin, and then GSP (200 mg kg(-1) body weight) was administrated for four weeks. Blood glucose, glycosylated hemoglobin (HbA1c) and also the levels of lipid peroxidation and antioxidant enzymes were examined in the heart tissues of all groups. Oral administration of GSP to diabetic rats significantly reduced (p < 0.05) heart weight, blood glucose, HbA1c and lipid peroxidation level, but increased (p < 0.05) body weight and activities antioxidant enzymes when compared to diabetic group. The results indicated that GSP could be useful for prevention or early treatment of cardiac disorder caused by diabetes. PMID- 26261707 TI - Connexin-43: A possible mediator of heat stress effects on ram Sertoli cells. AB - Sertoli cells are an essential group of cells in seminiferous epithelium which provide nutritional and structural supports for spermatogenic cells via cell junctions. In this study, the gene expression of connexin-43, the most abundantly distributed gap junction protein of cells, was investigated in ram Sertoli cells under mild and severe heat stresses with real-time quantitative PCR. Sertoli cells were isolated from testes of 10 lambs. After culture and 3 passages, they were treated with mild (39 C) and severe (42 C) heat stress for 6 hr. The results showed a significant reduction in the percentage of live cells under severe heat stress compared to the control group (32 C), (p <0.05). Relative quantification analysis revealed significantly higher (3.80 fold increase) values of connexin-43 transcripts in severely heat stressed group than control group (p <0.05). It is concluded that challenging Sertoli cells with 42 C heat could threaten their survival, and overexpression of connexin-43 may cause dysfunction of Sertoli cells due to heat stress. These findings can be useful to identify the molecular mechanisms involved in adverse effects of heat stress on male reproduction and enhance our understanding of its pathogenesis. PMID- 26261708 TI - Changes of stress oxidative enzymes in rat mammary tissue, blood and milk after experimental mastitis induced by E. coli lipopolysaccharide. AB - The present study investigated the effects of E. coli lipopolysaccharide (LPS) induced mastitis model in rat on the activity of antioxidant enzyme systems. To achieve this purpose, E. coli LPS were infused into the mammary gland of 12 rats 72 hr postpartum and compared with 12 rats in control group infused intramammary placebo sterile pyrogene - free, physiological saline. The antioxidant activities of the enzymes, superoxide dismutase, glutathione peroxidase, and catalase together with ?malondialdehyde (MDA) level were assayed in blood serum, milk and mammary tissue. Results obtained showed that, the antioxidant enzyme activities in milk, blood serum and mammary tissue were significantly decreased while the level of MDA, the indicator of lipid peroxidation were significantly increased following intramammary inoculation of LPS compared to the control animals. Histopathological examination also revealed the infiltration of inflammatory cells in mammary tissue and disruption of acinar structure and acinar lumina in mastitic rats. The results indicated that E. coli LPS-induced mastitis could alter antioxidant enzymes and increase lipid peroxidation. PMID- 26261709 TI - Modification of egg yolk fatty acids profile by using different oil sources. AB - The study was conducted to evaluate the effects of different dietary oil sources supplementation on laying hens' performance and fatty acids profile of egg yolks. Seventy-two 23-week-old laying hens (Tetra-SL) divided into six experimental diets (four replicates and three birds per replication) in a completely randomized design for nine weeks. Experimental diets were included: 1) control (no oil), 2) 3.00% fish oil, 3) 3.00% olive oil, 4) 3.00% grape seed oil, 5) 3.00% canola oil, and 6) 3.00% soybean oil. The diets were similar in terms of energy and protein. Egg production, egg mass, egg weight, feed intake, feed conversion ratio and fatty acid composition of egg yolk were determined at the end of the trial. The results indicated that the performance parameters were not significantly different between treatments in the entire period (p > 0.05). However, fatty acids profiles of yolk were affected by experimental diets (p < 0.05). Fish oil significantly reduced omega-6 fatty acids and increased docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in egg yolk. Also canola oil increased linolenic acid content in the egg yolk. In conclusion, fish oil increased omega-3 long-chain fatty acids and decreased omega-6 to omega-3 ratio in eggs which may have beneficial effects on human health. PMID- 26261710 TI - A survey of feline behavioral problems in Tehran. AB - Behavioral problems in cats have drawn more attention in recent years since they affect the cat-owner relationship. This study was designed to study the rate of cats with undesirable behaviors according to their owners. Frequency of behavioral problems in 167 cats attending Small Animal Hospital, Faculty of Veterinary Medicine, University of Tehran, was evaluated using a questionnaire. According to the results, 94.6% of owners reported that their cats have exhibited at least one undesirable behavior. Fearfulness, attention seeking, aggression towards other cats/people, scratching, and elimination problems were the most prevalent behavioral complaints reported by the owners; whereas obsessive behaviors were the least common behavioral complaints. In addition, data analysis suggested that age, breed, outdoor access, owner reaction towards the behavior and the cat's interaction with other cats/people might have been associated with the development of some behavioral problems in cats. Considerable rate of undesirable behaviors in domestic cats in Iran is important enough to highlight the significance of veterinary intervention. PMID- 26261711 TI - The European hedgehog (Erinaceus europaeus), as a reservoir for helminth parasites in Iran. AB - From April 2009 to December 2011, 44 dead hedgehogs (Erinaceus europaeus) were collected incidentally from areas of Urmia, Iran. The overall prevalence of helminth infections was 95.0%. Specific parasites and their prevalences were: Physaloptera clausa (93.0%), Crenosoma striatum (61.0%), Capillaria aerophila (9.0%), Capillarias spp. (4.0%), Brachylaemus erinacei (2.0%) and Hymenolepis erinacei (16.0%). There were no significant differences in helminth occurrence between hedgehog sexes, either in single or in mixed infections (p > 0.05). The mixed infection involving Crenosoma striatum and P. clausa occurred significantly more frequently than other mixed infection (p < 0.05). There were significant differences in prevalence among seasons, with the highest prevalence in summer and spring especially among P. clausa and C. striatum (p < 0.05). PMID- 26261712 TI - Determination of hazardous substances in food basket eggs in Tehran, Iran: A preliminary study. AB - Extensive distribution of hazardous substances in food chain and the deleterious effect of their residues on public health are a great concern of the society. Chicken eggs, as one of the most popular food commodities, in different parts of Tehran (Iran) were analyzed for two groups of hazardous substances including some organochlorine pesticides (OC) such as aldrin, lindane, dieldrin, dichlorodiphenyltrichloroethane, heptachlor and endusulfan) and heavy metals namely mercury (Hg), arsenic (As), lead (Pb), copper (Cu), cadmium (Cd), nickel (Ni) and chromium (Cr). Gas chromatography- electron capture detector, hydride generation atomic absorption spectrometry, cold- vapor atomic absorption spectrometry and conductively coupled plasma atomic optical spectrometry were used to determine the levels of OCs, As, Hg and the others, respectively. For OCs, the results revealed none of the levels were more than maximum residues levels (MRLs), but three of them (Aldrin, lindane and endusulphan) were detectable. Moreover, 100% of 50 eggs had heavy metals with levels higher than limit of detection of the procedure. The levels of Pb and Hg in all eggs and Cd in 47% of samples were more than MRLs. It seems that the regular national monitoring of egg producing chain specially the quality of chicken feed should be taken into account seriously in order to safeguard public general health. PMID- 26261713 TI - Growth and antioxidant status of broilers fed supplemental lysine and pyridoxine under high ambient temperature. AB - Three levels of lysine (90, 100 and 110% of Ross requirement) and of pyridoxine (3, 6 and 9 mg kg(-1)) were used in a 3 * 3 factorial experiment to investigate the growth and blood antioxidant ability of broilers under high ambient temperature. None of the dietary supplements affected the weight gain during the starter and grower periods. Although no significant differences were detected between the treatments during the entire period, high lysine level fed birds had a lower weight gain. At any levels of pyridoxine, high lysine fed birds were lighter than others. Neither the lysine nor pyridoxine changed the feed intake or feed conversion ratio during the starter, grower and entire period. However there was no significant difference between the treatments for blood malondialdehyde (MDA) concentration, medium lysine fed birds had lower blood MDA than other ones. No significant effects on blood triglyceride, total protein and blood superoxide dismutase activity were indicated with addition of any lysine or pyridoxine level. Medium lysine fed birds had decreased blood glutathione peroxidase activity compared to the birds of other treatments. It was concluded that providing the proposed dietary lysine requirement of Ross strain during heat stress ensuring the best body weight gain and body antioxidant ability. Higher lysine level causes the retarded weight gain due to higher excretion of arginine from the body and consequently higher lipid peroxidation. PMID- 26261714 TI - Comparative evaluation between hypericin (hypiran) and fluoxetine in treatment of companion dogs with tail chasing. AB - The aim of the present study was to compare the effects of hypericin and fluoxetine in the treatment of companion dogs with tail chasing in Ahvaz district. In the present survey, eighteen dogs with tail chasing were assigned into three equal groups for a three-year period. The dogs were randomly classified based on different treatment groups. During 15 weeks, dogs of group A were given 0.05 mg kg(-1) hypericin orally and dogs of group B received 1 mg kg( 1) fluoxetine, orally. The group C was the control group. Changes in signs of tail chasing were weekly reported by the owners or a veterinarian. Treatment periods were assessed in five intervals: weeks 1-3, 4-6, 7-9, 10-12 and weeks 13 15, respectively. Hypericin (group A) was significantly more effective in the treatment of tail chasing compared with fluoxetine (group B), (p = 0.043). Statistical analysis revealed a significant difference in each group between weeks 1-3 (X(2) = 8.8, p = 0.01), 4-6 (X(2) = 9.1, p = 0.01), 7-9 (X(2) = 7.4, p = 0.03), 10-12 (X(2) = 10.4, p = 0.005) and 13-15 (X(2) = 12.5, p = 0.002). Improvement of behavior in the dogs of group A was significant compared with group B, between weeks 10-12 (X(2) = 5.4, p = 0.02) and 13-15 (X(2) = 7.2, p = 0.007). In conclusion, our survey showed that hypericin was more effective than fluoxetine in controlling signs of tail chasing. PMID- 26261715 TI - The effect of short-time microwave exposures on Listeria monocytogenes inoculated onto chicken meat portions. AB - Listeria monocytogenes can be found throughout the environment and in many foods. It is associated primarily with meat and animal products. Listeria monocytogenes has become increasingly important as a food-borne pathogen. The aim of this study was to evaluate the effect of microwave (MW) treatment of chicken meat samples which were inoculated with L. monocytogenes. Drumettes of broiler carcasses were soaked in fully growth of L. monocytogenes in Brain-Heart Infusion broth. The swab samples were taken from the inoculated samples, after various times of radiation (10, 20, 30, 40, 50, 60, 70 and 80 sec), using a domestic MW oven at full power. Following exposures, viable counts and surface temperature measurements were performed. The bacterial counts were performed on Oxford agar. The results indicated that equal or longer than 60 sec exposures of chicken portions to MW heating which enhances the median surface temperature more than 74 C could eliminate the superficial contamination of chicken meat with L. monocytogenes. Statistical analysis showed samples with equal or longer than 60 sec exposures to MW heating had significant decrease in population of inoculated bacteria compared with positive control group (p < 0.05). Pearson correlation showed a significant correlation between the bacterial population and temperature of samples due to MW exposure (p < 0.001, r = - 0.879 and r (2) = 0.773). PMID- 26261716 TI - Visceral urate deposition in a little bittern (Ixobrychus minutus). AB - Visceral urate deposition (visceral gout) is a common finding during post-mortem examination of poultry. Rare cases of visceral gout may occur in wild birds. A rare case of visceral urate deposition in a little bittern (Ixobrychus minutus) is reported here. In May 2013, carcass of a little bittern was submitted for necropsy to the Clinic of Poultry Diseases (Faculty of Veterinary Medicine, Razi University) by local authorities of Iran Department of Environment. At necropsy, white chalky deposits were observed on the heart and thoracic air sacs of the bird. To confirm the presence of urates, chalky deposits were collected from pericardium and tested by muerxide test. Heart and kidneys were sampled, preserved in 10% neutral-buffered formalin solution and submitted to laboratory for histopathology. Murexide test was positive for presence of uric acid in chalky deposits collected from pericardium. Light microscopy of affected organs confirmed the condition as visceral urate deposition. To the best of our knowledge, this is the first report on the occurrence of visceral urate deposition in a little bittern. PMID- 26261717 TI - Surgical treatment and a unique management of rostral mandibular fracture with cerclage wire in a horse. AB - A 3-year-old Arabian colt was presented for a major gingiva wound at the right rostral part of mandible. After clinical assessments, rostral mandibular fracture was determined. Stabilization of fractured region was achieved via cerclage wire application under general anesthesia. Fixation wires were left in place for 6 weeks. A 3 -month follow up revealed complete fracture healing. The purpose of this case report was to give clinical information about rostral mandibular fractures and treatment of these fractures and nutrition protocol in a horse, as this fracture is of the most common type of jaw fracture sustained by young horses. PMID- 26261718 TI - Micropublications: a semantic model for claims, evidence, arguments and annotations in biomedical communications. AB - BACKGROUND: Scientific publications are documentary representations of defeasible arguments, supported by data and repeatable methods. They are the essential mediating artifacts in the ecosystem of scientific communications. The institutional "goal" of science is publishing results. The linear document publication format, dating from 1665, has survived transition to the Web. Intractable publication volumes; the difficulty of verifying evidence; and observed problems in evidence and citation chains suggest a need for a web friendly and machine-tractable model of scientific publications. This model should support: digital summarization, evidence examination, challenge, verification and remix, and incremental adoption. Such a model must be capable of expressing a broad spectrum of representational complexity, ranging from minimal to maximal forms. RESULTS: The micropublications semantic model of scientific argument and evidence provides these features. Micropublications support natural language statements; data; methods and materials specifications; discussion and commentary; challenge and disagreement; as well as allowing many kinds of statement formalization. The minimal form of a micropublication is a statement with its attribution. The maximal form is a statement with its complete supporting argument, consisting of all relevant evidence, interpretations, discussion and challenges brought forward in support of or opposition to it. Micropublications may be formalized and serialized in multiple ways, including in RDF. They may be added to publications as stand-off metadata. An OWL 2 vocabulary for micropublications is available at http://purl.org/mp. A discussion of this vocabulary along with RDF examples from the case studies, appears as OWL Vocabulary and RDF Examples in Additional file 1. CONCLUSION: Micropublications, because they model evidence and allow qualified, nuanced assertions, can play essential roles in the scientific communications ecosystem in places where simpler, formalized and purely statement-based models, such as the nanopublications model, will not be sufficient. At the same time they will add significant value to, and are intentionally compatible with, statement-based formalizations. We suggest that micropublications, generated by useful software tools supporting such activities as writing, editing, reviewing, and discussion, will be of great value in improving the quality and tractability of biomedical communications. PMID- 26261719 TI - Prevalence and factors associated with undernutrition and anaemia among school children in Durbete Town, northwest Ethiopia. AB - BACKGROUND: Information about risk factors of undernutrition and anaemia is useful to design appropriate strategies to control the health problems. In this study, the prevalence and factors associated with undernutrition and anaemia were assessed among school children in Abchikeli and Ayalew Mekonnen Elementary Schools, northwest Ethiopia, in February and March 2010. METHODS: A cross sectional study was carried out among 384 school children. Stool samples were examined using single Kato-Katz slide and nutritional status was determined using anthropometry technique. A pre-tested standardized questionnaire was used to gather information on the socio-demographic and the socio-economic status of the school children. Multivariate logistic regression analysis was used to quantify the association of intestinal helminth infection and socio-demographic and socio economic factors with undernutrition and anaemia. RESULTS: Out of 384 children examined, 32.3 % were undernourished (27.1 % underweight and 11.2 % stunted) and 10.7 % were anaemic. The odds of stunting were approximately seven times higher in children of ages 10 to 14 [Adjusted Odds Ratio (AOR) = 6.93, 95 % CI = 2.60, 18.46] and 2.5 times higher in males [AOR = 2.50, 95 % CI = 1.24, 5.07] than children of ages 5 to 9 and females, respectively. The odds of underweight was three times higher in children who did not wash their hands before eating compared to those who did wash their hands [AOR = 3.13, 95 % CI = 1.19, 8.17]. The chance of anaemia was nine times higher in children who were infected with hookworms compared to those who were not infected with any helminth species [AOR = 8.87, 95 % CI = 2.28, 34.58]. The odds of being undernourished and anemic were similar among children with different socio-economic status. CONCLUSIONS: Undernutrition and anaemia are public health problems of school-age children in Durbete Town. Health education and provision of additional food supplements would be important to reduce the problem of undernutrition among school-age children in the town. Deworming of children in the town would also have additional impact on reducing the level of anaemia. PMID- 26261720 TI - Effects of magnetic resonance-guided high-intensity focused ultrasound ablation on bone mechanical properties and modeling. AB - BACKGROUND: Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a promising technique for palliative treatment of bone pain. In this study, the effects of MR-HIFU ablation on bone mechanics and modeling were investigated. METHODS: A total of 12 healthy rat femurs were ablated using 10 W for 46 +/- 4 s per sonication with 4 sonications for each femur. At 7 days after treatments, all animals underwent MR and single photon emission computed tomography/computed tomography (SPECT/CT) imaging. Then, six animals were euthanized. At 1 month following ablations, the remaining six animals were scanned again with MR and SPECT/CT prior to euthanization. Thereafter, both the HIFU-treated and contralateral control bones of three animals from each time interval were processed for histology, whereas the remaining bones were subjected to micro-CT (MUCT), three-point bending tests, and micro-finite element (micro-FE) analyses. RESULTS: At 7 days after HIFU ablations, edema formation around the treated bones coupled with bone marrow and cortical bone necrosis was observed on MRI and histological images. SPECT/CT and MUCT images revealed presence of bone modeling through an increased uptake of (99m)Tc-MDP and formation of woven bone, respectively. At 31 days after ablations, as illustrated by imaging and histology, healing of the treated bone and the surrounding soft tissue was noted, marked by decreased in amount of tissue damage, formation of scar tissue, and sub periosteal reaction. The results of three-point bending tests showed no significant differences in elastic stiffness, ultimate load, and yield load between the HIFU-treated and contralateral control bones at 7 days and 1 month after treatments. Similarly, the elastic stiffness and Young's moduli determined by micro-FE analyses at both time intervals were not statistically different. CONCLUSIONS: Multimodality imaging and histological data illustrated the presence of HIFU-induced bone damage at the cellular level, which activated the bone repair mechanisms. Despite that, these changes did not have a mechanical impact on the bone. PMID- 26261721 TI - Pancreas cancer: why bother? PMID- 26261722 TI - Imaging preoperatively for pancreatic adenocarcinoma. AB - Pancreatic cancer is a highly lethal malignancy which is increasing in incidence and mortality. The fourth leading cause of cancer death in the U.S., pancreatic cancer is projected to become the second leading cause of cancer death by 2020. Patients with pancreatic cancer have an abysmal 5-year survival of 6%, and 90% of these patients eventually die from the disease. This is in large part due to the commonly advanced stage of disease at the time of diagnosis. Currently, the only potentially curative therapy for pancreatic carcinoma is complete surgical resection. Patients who undergo incomplete resection with residual disease have similar survival rates to those patients with metastatic disease and should be spared this relatively morbid surgery. Thus, the key to impacting prognosis is the detection of smaller and earlier stage lesions, and the key to optimal management is accurately determining which patients have potentially resectable surgery and which patients would not benefit from surgery. Cross-sectional imaging plays an essential role in both the diagnosis and appropriate staging of pancreatic carcinoma. The diagnosis and staging of pancreatic adenocarcinoma is performed with cross-sectional imaging. Multi-detector computed tomography (MDCT) is the most commonly used, best-validated imaging modality for the diagnosis and staging of pancreatic cancer. Modern contrast-enhanced magnetic resonance imaging (MRI) has been demonstrated to be equivalent to MDCT in detection and staging of pancreatic cancer. Endoscopic ultrasound (EUS) is very sensitive for detecting pancreatic masses; however, due to limitations in adequate overall abdominal staging, it is generally used in addition to or after MDCT. Transabdominal ultrasound and positron emission tomography/computed tomography (PET/CT) have limited roles in the diagnosis and staging of pancreatic cancer. Preoperative imaging is used to characterize patients as having resectable disease, borderline resectable disease, locally advanced disease (unresectable) and metastatic disease (unresectable). As the definitions of borderline resectable and unresectable may vary from institution to institution and within institutions, it is essential to accurately assess and describe the factors relevant to staging including: local extent of tumor, vascular involvement, lymph node involvement and distant metastatic disease. To facilitate this, standardized reporting templates for pancreatic ductal adenocarcinoma have been created and published. Structured reporting for pancreatic cancer has been reported to provide superior evaluation of pancreatic cancer, facilitate surgical planning, and increase surgeons' confidence about tumor resectability. PMID- 26261723 TI - Pancreatic adenocarcinoma pathology: changing "landscape". AB - Pancreatic cancer is a devastating disease. At time of diagnosis the disease is usually advanced and only a minority of patients are eligible for surgical resection. The overall 5-year survival is 6%. However, survival of patients with early stage pancreatic cancer is significantly better. To improve the prognosis of patients with pancreatic cancer, it is essential to diagnose and treat pancreatic cancer in the earliest stage. Prevention of pancreatic cancer by treating noninvasive precursor lesions just before they invade tissues can potentially lead to even better outcomes. Pancreatic carcinogenesis results from a stepwise progression in which accumulating genetic alterations drive neoplastic progression in well-defined precursor lesions, ultimately giving rise to an invasive adenocarcinoma. A thorough understanding of the genetic changes that drive pancreatic carcinogenesis can lead to identification of biomarkers for early detection and targets for therapy. Recent next-generation sequencing (NGS) studies have shed new light on our understanding of the natural history of pancreatic cancer and the precursor lesions that give rise to these cancers. Importantly, there is a significant window of opportunity for early detection and treatment between the first genetic alteration in a cell in the pancreas and development of full-blown pancreatic cancer. The current views on the pathology and genetics of pancreatic carcinogenesis that evolved from studies of pancreatic cancer and its precursor lesions are discussed in this review. PMID- 26261724 TI - Diagnosis and management of cystic lesions of the pancreas. AB - Pancreatic cystic lesions (PCLs) are being increasingly identified in recent years. They show a wide spectrum of imaging and clinical features. The diagnosis and discrimination of these lesions are very important because of the risk for concurrent or later development of malignancy. PCLs are usually first diagnosed and characterized by conventional imaging modalities such as trans-abdominal ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI). However, their ability to differentiate the benign and malignant lesions remains limited. Endoscopic US may be more helpful for the diagnosis and differentiation of PCLs because of its high resolution and better imaging characteristics than cross-sectional imaging modalities. It also allows for fine needle aspiration (FNA) of cystic lesions for biochemical, cytological and DNA analysis that might be further helpful for diagnosis and differentiation. The management options of PCLs are to observe, endoscopic treatment or surgical resection. However, the decision for management is sometimes hampered by limitations in current diagnostic and tissue sampling techniques. As further diagnostic and non-invasive management options become available, clinical decision-making will become much easier for these lesions. PMID- 26261725 TI - Management of periampullary adenocarcinoma by pancreaticoduodenectomy at a regional teaching hospital. AB - BACKGROUND: Periampullary adenocarcinoma (PA) includes: pancreatic, duodenal and ampullary adenocarcinoma; and cholangiocarcinoma. Pancreaticoduodenectomy (PD) is required for cure of PA. Previous studies demonstrated the likelihood of cure increases when a microscopically negative (R0) margin is achieved. Clearance of the superior mesenteric artery (SMA) margin has been identified as the most critical margin in PD. Some authors have emphasized the importance of certain techniques to clear the SMA margin. Neither the degree to which these techniques have been incorporated nor their impact on margin status and survival has been described. We hypothesized that use of techniques focusing on clearing the SMA margin would result in higher R0 resection rates and improved survival after PD in patients with PA. METHODS: A retrospective study was performed on patients from 1/1/1985 until 7/31/2007. Data on patient demographics, clinical presentation, preoperative treatment, operative technique, margins, and postoperative outcomes were collected. Ninety-three patients were identified for inclusion in the study. Three approximately equal groups were created for analysis. RESULTS: The overall survival (OS) for the entire cohort was 19 months and was not different among the groups studied. Margins were microscopically negative in 81% of cases. The percentage of node-positive cases increased during the time period, as did the number of lymph nodes (LNs) examined (P=0.017). The use of pylorus-preserving PD decreased (P=0.001) while resection of the superior mesenteric/portal vein (SMV/PV) increased during the study period. We observed an increase in descriptions of the clearance of the anterior aspect of the aorta and inferior vena cava (IVC), dissection to the right side of the SMA, dissection to the origin of the SMA and intra-operative identification of the SMA margin. Dissecting to the SMA did not change the likelihood of achieving an R0 margin. OS was improved after R0 resections (R0: 21 months vs. R1/2: 10 months) but this difference was not statistically significant (P=0.099). There was no association between margin status and OS. Changes in the pathology reporting of margins were observed, with statistically significant increases in the percentage of cases in which the SMA, common bile duct and pancreatic neck margins were separately reported. However, the SMA margin was separately reported in only 26% of pathology reports. CONCLUSIONS: The operative techniques used in PD at this institution have changed over time. The increasing frequency of dissection to the SMA and identification of the SMA margin by both surgeon and pathologist suggest an increased attention to the SMA margin. This shift did not result in significant improvements in survival or margin status, but it is consistent with the recognition of the importance of the SMA margin. Our analysis has also identified areas of potential improvement in the ways in which operative and pathology reports for PD are generated. PMID- 26261726 TI - Robotic pancreaticoduodenectomy for pancreatic adenocarcinoma: role in 2014 and beyond. AB - Minimally invasive surgery (MIS) for pancreatic adenocarcinoma has found new avenues for performing pancreaticoduodenectomy (PD) procedures, a historically technically challenging operation. Multiple studies have found laparoscopic PD to be safe, with equivalent oncologic outcomes as compared to open PD. In addition, several series have described potential benefits to minimally invasive PD including fewer postoperative complications, shorter hospital length of stay, and decreased postoperative pain. Yet, despite these promising initial results, laparoscopic PDs have not become widely adopted by the surgical community. In fact, the vast majority of pancreatic resections performed in the United States are still performed in an open fashion, and there are only a handful of surgeons who actually perform purely laparoscopic PDs. On the other hand, robotic assisted surgery offers many technical advantages over laparoscopic surgery including high definition, 3-D optics, enhanced suturing ability, and more degrees of freedom of movement by means of fully-wristed instruments. Similar to laparoscopic PD, there are now several case series that have demonstrated the feasibility and safety of robotic PD with seemingly equivalent short-term oncologic outcomes as compared to open technique. In addition, having the surgeon seated for the procedure with padded arm-rests, there is an ergonomic advantage of robotics over both open and laparoscopic approaches, where one has to stand up for prolonged periods of time. Future technologic innovations will likely focus on enhanced robotic capabilities to improve ease of use in the operating room. Last but not least, robotic assisted surgery training will continue to be a part of surgical education curriculum ensuring the increased use of this technology by future generations of surgeons. PMID- 26261727 TI - Laparoscopic distal pancreatectomy for adenocarcinoma: safe and reasonable? AB - As a result of technological advances during the past two decades, surgeons now use minimally invasive surgery (MIS) approaches to pancreatic resection more frequently, yet the role of these approaches for pancreatic ductal adenocarcinoma resections remains uncertain, given the aggressive nature of this malignancy. Although there are no controlled trials comparing MIS technique to open surgical technique, laparoscopic distal pancreatectomy for pancreatic adenocarcinoma is performed with increasing frequency. Data from retrospective studies suggest that perioperative complication profiles between open and laparoscopic distal pancreatectomy are similar, with perhaps lower blood loss and fewer wound infections in the MIS group. Concerning oncologic outcomes, there appear to be no differences in the rate of achieving negative margins or in the number of lymph nodes (LNs) resected when compared to open surgery. There are limited recurrence and survival data on laparoscopic compared to open distal pancreatectomy for pancreatic adenocarcinoma, but in the few studies that assess long term outcomes, recurrence rates and survival outcomes appear similar. Recent studies show that though laparoscopic distal pancreatectomy entails a greater operative cost, the associated shorter length of hospital stay leads to decreased overall cost compared to open procedures. Multiple new technologies are emerging to improve resection of pancreatic cancer. Robotic pancreatectomy is feasible, but there are limited data on robotic resection of pancreatic adenocarcinoma, and outcomes appear similar to laparoscopic approaches. Additionally fluorescence-guided surgery represents a new technology on the horizon that could improve oncologic outcomes after resection of pancreatic adenocarcinoma, though published data thus far are limited to animal models. Overall, MIS distal pancreatectomy appears to be a safe and reasonable approach to treating selected patients with pancreatic ductal adenocarcinoma, though additional studies of long-term oncologic outcomes are merited. We review existing data on MIS distal pancreatectomy for pancreatic ductal adenocarcinoma. PMID- 26261728 TI - Neoadjuvant therapy for localized pancreatic cancer: guiding principles. AB - The management of localized pancreatic cancer (PC) remains controversial. Historically, patients with localized disease have been treated with surgery followed by adjuvant therapy (surgery-first approach) under the assumption that surgical resection is necessary, even if not sufficient for cure. However, a surgery-first approach is associated with a median overall survival of only 22-24 months, suggesting that a large proportion of patients with localized PC have clinically occult metastatic disease. As a result, adjuvant therapy has been recommended for all patients with localized PC, but in actuality, it is often not received due to the high rates of perioperative complications associated with pancreatic resections. Recognizing that surgery may be necessary but usually not sufficient for cure, there has been growing interest in neoadjuvant treatment sequencing, which benefits patients with both localized and metastatic PC by ensuring the delivery of oncologic therapies which are commensurate with the stage of disease. For patients who have clinically occult metastatic disease, neoadjuvant therapy allows for the early delivery of systemic therapy and avoids the morbidity and mortality of a surgical resection which would provide no oncologic benefit. For patients with truly localized disease, neoadjuvant therapy ensures the delivery of all components of the multimodality treatment. This review details the rationale for a neoadjuvant approach to localized PC and provides specific recommendations for both pretreatment staging and treatment sequencing for patients with resectable and borderline resectable (BLR) disease. PMID- 26261729 TI - Novel adjuvant therapies for pancreatic adenocarcinoma. AB - Contemporary adjuvant therapy for pancreatic cancer patients following surgical resection includes chemotherapy and chemoradiotherapy. However, the median survival remains approximately 20 months despite multi-modality treatment using gemcitabine or fluoropyrimidine systemic chemotherapy. Adjuvant randomized trials are currently underway to evaluate cytotoxic combinations found to be active in advanced disease including FOLFIRINOX, gemcitabine/nab-paclitaxel and gemcitabine/capecitabine. Immunotherapy using genetically engineered cell-based vaccines had shown promise in resected pancreatic cancer patients during early phase trials, and algenpantucel-L vaccine is currently being evaluated in adjuvant setting in a randomized trial. This review focuses on novel adjuvant therapies currently in clinical evaluation. PMID- 26261730 TI - Adjuvant radiation therapy for pancreatic cancer: a review of the old and the new. AB - Surgery represents the only potential curative treatment option for patients diagnosed with pancreatic adenocarcinoma. Despite aggressive surgical management for patients deemed to be resectable, rates of local recurrence and/or distant metastases remain high, resulting in poor long-term outcomes. In an effort to reduce recurrence rates and improve survival for patients having undergone resection, adjuvant therapies (ATs) including chemotherapy and chemoradiation therapy (CRT) have been explored. While adjuvant chemotherapy has been shown to consistently improve outcomes, the data regarding adjuvant radiation therapy (RT) is mixed. Although the ability of radiation to improve local control has been demonstrated, it has not always led to improved survival outcomes for patients. Early trials are flawed in their utilization of sub-optimal radiation techniques, limiting their generalizability. Recent and ongoing trials incorporate more optimized RT approaches and seek to clarify its role in treatment strategies. At the same time novel radiation techniques such as intensity modulated RT (IMRT) and stereotactic body RT (SBRT) are under active investigation. It is hoped that these efforts will lead to improved disease-related outcomes while reducing toxicity rates. PMID- 26261731 TI - Pain management of pancreatic head adenocarcinomas that are unresectable: celiac plexus neurolysis and splanchnicectomy. AB - BACKGROUND: Pancreatic adenocarcinoma is often incurable at the time of diagnosis. For patients with unresectable or recurrent disease, palliation of pain is a key component of care. Medical management with narcotics has numerous side effects and may be ineffective. Interventions for pain control include celiac plexus neurolysis (CPN) and splanchnicectomy. The purpose of this review is to outline pertinent anatomy, techniques, side effects, complications, and efficacy of interventions for palliation of pain from pancreatic cancer. METHODS: We reviewed current literature, as well as our own patients, to assess the role and outcomes of CPN and splanchnicectomy. Short descriptions of procedural techniques and functional illustrations are provided. RESULTS: Both CPN and splanchnicectomy have excellent outcomes with regard to pain control. Quality of life and survival, however, have not been conclusively demonstrated to improve with either technique. Data regarding head-to-head comparisons of the two interventions is lacking. CONCLUSIONS: Patients with incurable pancreatic carcinoma should be offered either CPN or splanchnicectomy when medical management with narcotics has failed. PMID- 26261732 TI - Current position of vasoconstrictor and albumin infusion for type 1 hepatorenal syndrome. AB - Spontaneous bacterial peritonitis (SBP), refractory ascites, hepatorenal syndrome (HRS), hyponatremia and hepatic encephalopathy are complications which frequently happen during a clinical course of decompensated cirrhosis. Splanchnic and peripheral vasodilatation, increased intrarenal vasoconstriction and impaired cardiac responsive function are pathological changes causing systemic and hemodynamic derangement. Extreme renal vasoconstriction leads to severe reduction of renal blood flow and glomerular filtration rate, which finally evolves into the clinical feature of HRS. Clinical manifestations of type 1 and type 2 HRS come to medical attention differently. Patients with type 1 HRS present as acute kidney injury whereas those with type 2 HRS will have refractory ascites as the leading problem. Prompt diagnosis of type 1 HRS can halt the progression of HRS to acute tubular necrosis if the combined treatment of albumin infusion and vasoconstrictors is started timely. HRS reversal was seen in 34%-60% of patients, followed with decreasing mortality. Baseline serum levels of creatinine less than 5 mg/dL, bilirubin less than 10 mg/dL, and increased mean arterial pressure of over 5 mmHg by day 3 of the combined treatment of vasoconstrictor and albumin are the predictors of good response. Type 1 HRS can be prevented in some conditions such as albumin infusion in SBP, prophylactic antibiotics for upper gastrointestinal hemorrhage, albumin replacement after large volume paracentesis in cirrhotic patients with massive ascites. The benefit of albumin infusion in infection with primary source other than SBP requires more studies. PMID- 26261735 TI - Nociceptin effect on intestinal motility depends on opioid-receptor like-1 receptors and nitric oxide synthase co-localization. AB - AIM: To study the effect of the opioid-receptor like-1 (ORL1) agonist nociceptin on gastrointestinal (GI) myenteric neurotransmission and motility. METHODS: Reverse transcriptase - polymerase chain reaction and immunohistochemistry were used to localize nociceptin and ORL1 in mouse tissues. Intracellular electrophysiological recordings of excitatory and inhibitory junction potentials (EJP, IJP) were made in a chambered organ bath. Intestinal motility was measured in vivo. RESULTS: Nociceptin accelerated whole and upper GI transit, but slowed colonic expulsion in vivo in an ORL1-dependent manner, as shown using [Nphe(1)]NOC and AS ODN pretreatment. ORL1 and nociceptin immunoreactivity were found on enteric neurons. Nociceptin reduced the EJP and the nitric oxide sensitive slow IJP in an ORL1-dependent manner, whereas the fast IJP was unchanged. Nociceptin further reduced the spatial spreading of the EJP up to 2 cm. CONCLUSION: Compounds acting at ORL1 are good candidates for the future treatment of disorders associated with increased colonic transit, such as diarrhea or diarrhea-predominant irritable bowel syndrome. PMID- 26261734 TI - Antioxidants in liver health. AB - Liver diseases are a worldwide medical problem because the liver is the principal detoxifying organ and maintains metabolic homeostasis. The liver metabolizes various compounds that produce free radicals (FR). However, antioxidants scavenge FR and maintain the oxidative/antioxidative balance in the liver. When the liver oxidative/antioxidative balance is disrupted, the state is termed oxidative stress. Oxidative stress leads to deleterious processes in the liver and produces liver diseases. Therefore, restoring antioxidants is essential to maintain homeostasis. One method of restoring antioxidants is to consume natural compounds with antioxidant capacity. The objective of this review is to provide information pertaining to various antioxidants found in food that have demonstrated utility in improving liver diseases. PMID- 26261736 TI - Beverage intake preference and bowel preparation laxative taste preference for colonoscopy. AB - AIM: To examine whether non-alcoholic beverage intake preferences can guide polyethylene glycol (PEG)-based bowel laxative preparation selection for patients. METHODS: We conducted eight public taste test sessions using commercially procured (A) unflavored PEG, (B) citrus flavored PEG and (C) PEG with ascorbate (Moviprep). We collected characteristics of volunteers including their beverage intake preferences. The volunteers tasted the laxatives in randomly assigned orders and ranked the laxatives as 1(st), 2(nd), and 3(rd) based on their taste preferences. Our primary outcome is the number of 1(st) place rankings for each preparation. RESULTS: A total of 777 volunteers completed the study. Unflavored PEG was ranked as 1(st) by 70 (9.0%), flavored PEG by 534 (68.7%) and PEG with ascorbate by 173 (22.3%) volunteers. Demographic, lifestyle characteristics and beverage intake patterns for coffee, tea, and carbonated drinks did not predict PEG-based laxative preference. CONCLUSION: Beverage intake pattern was not a useful guide for PEG-based laxative preference. It is important to develop more tolerable and affordable bowel preparation laxatives for colonoscopy. Also, patients should taste their PEG solution with and without flavoring before flavoring the entire gallon as this may give them more opportunity to pick a pattern that may be more tolerable. PMID- 26261737 TI - Gastrointestinal Kaposi's sarcoma: Case report and review of the literature. AB - Kaposi's sarcoma (KS) of the gastrointestinal tract is not an uncommon disease among individuals with acquired immunodeficiency syndrome (AIDS). The majority is asymptomatic, and for this reason, gastrointestinal KS (GI-KS) remains undiagnosed. With continued tumor growth, considerable variation in clinical presentation occurs including abdominal pain, nausea, vomiting, iron deficiency anemia (either chronic or frank gastrointestinal bleeding), and rarely mechanical obstruction alone or combined with bowel perforation. Endoscopy with biopsy allows for histological and immunohistochemical testing to confirm the diagnosis of GI-KS among those with clinical symptoms. In previous studies, dual treatment with highly active antiretroviral therapy and systemic chemotherapy have been associated with improved morbidity and mortality in individuals with visceral KS. Therefore, investigators have suggested performing screening endoscopies in select patients for early detection and treatment to improve outcome. In this review, we describe a 44 years old man with AIDS and cutaneous KS who presented for evaluation of postprandial abdominal pain, vomiting, and weight loss. On upper endoscopy, an extensive, infiltrative, circumferential, reddish mass involving the entire body and antrum of the stomach was seen. Histologic examination later revealed spindle cell proliferation, and confirmatory immunohistochemical testing revealed human herpes virus 8 latent nuclear antigen expression consistent with a diagnosis of gastric KS. Following this, we present a comprehensive review of literature on KS with emphasis on gastrointestinal tract involvement and management. PMID- 26261738 TI - Distal Radius Isoelastic Resurfacing Prosthesis: A Preliminary Report. AB - Background Here we present a preliminary case series of unicompartmental isoelastic resurfacing prosthesis of the distal radius to treat comminuted articular fractures of osteoporotic elderly patients. Materials and Methods Our study included 12 patients, mean age 76 years, who presented with comminuted osteoporotic distal radius fracture. Because of the severity of injury and poor bone quality; osteosynthesis was not deemed to be a good option. Description of Technique The surgery was performed through a dorsal approach. The subchondral bone of the entire distal radial articular was excised and a unicompartmental prosthesis was applied. Results At an average follow-up of 32 months, the pain was 2.8/10, Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) 37.4/100, grip strength in neutral 49.9%, in supination 59.0%, and in pronation 56.2% of the contralateral normal side. The wrist ranges of motion in flexion and extension were 56.1% and 79.3%, in supination and pronation 87.7% and 91.0% of the contralateral normal side. Two patients experienced a complex regional pain syndrome (CRPS) type II; these resolved spontaneously. One patient experienced distal radioulnar joint (DRUJ) stiffness, which improved after an ulna head resection. Finally, one patient required revision surgery after a secondary traumatic fracture. Radiographically; the average volar tilt was 9.8 degrees ; the average of radial inclination was 11.6 degrees . Conclusion The concept of a unicompartmental isoelastic resurfacing prosthesis offers a promising option for the treatment of comminuted, osteoporotic distal radius articular fractures of elderly patients. Level of Evidence IV. PMID- 26261739 TI - Primary Wrist Hemiarthroplasty for Irreparable Distal Radius Fracture in the Independent Elderly. AB - Background Volar plating for acute distal radius fractures (DRF) in the elderly has been recommended. Some studies have suggested that open reduction with internal fixation (ORIF) in this situation results in frequent complications. Our purposes were to provide a definition of irreparable DRF in independent elderly patients and to review the results of a preliminary retrospective series of wrist hemiarthroplasty (WHA) in this patient population. Materials Between 2011 and 2014, 11 consecutive independent elderly patients (12 wrists) with irreparable intra-articular DRF were treated with primary WHA at the acute stage. A resection of the ulnar head was associated in nine wrists. A total of 11 wrists with more than 2 years of follow-up form the basis of this paper. Description of Technique The approach was dorsal longitudinal. An osteotome longitudinally entered the dorsal aspect of the fracture medial to the Lister tubercle. Two thick osteoperiosteal flaps were elevated radially and ulnarly in a fashion similar to opening a book. The distal radius articular surface was excised. The implant was pressed into the radial canal with attention to restoring distal radius length. The two osteoperiosteal flaps were brought back together and sutured so as to close, again like a book, the osseous and soft tissues around the implant. Results At mean follow-up of 30 months, average visual analog scale (VAS) pain was 1/10. Mean QuickDASH (Disabilities of the Arm, Shoulder and Hand) score was 32, and mean Patient-Rated Wrist Evaluation (PRWE) score was 24. Mean forearm rotation arc was 151 degrees . Mean active flexion-extension arc was 60 degrees . Mean active extension was 34 degrees . Mean grip strength was 14 kg (64% of contralateral wrist). Mean Lyon wrist score was 73%. Bone healing around the implants was satisfactory in all but one case. Conclusions Out data suggest that treatment of irreparable DRF in the independent elderly patient with a bone preserving WHA may be a viable option. Longer-term follow-up and comparative studies are needed to confirm the validity of this concept. PMID- 26261733 TI - Primary biliary cirrhosis: From bench to bedside. AB - Primary biliary cirrhosis (PBC) is a chronic non-suppurative destructive intrahepatic cholangitis leading to cirrhosis after a protractive non cirrhotic stage. The etiology and pathogenesis are largely unknown and autoimmne mechanisms have been implicated to explain the pathological lesions. Many epitopes and autoantigens have been reported as crucial in the pathophysiology of the disease and T and B cells abnormalities have been described, the exact pathways leading to the destruction of small intrahepatic ductules are mostly speculative. In this review we examined the various epidemiologal and geoepidemiological data as well as the complex pathogenetic aspects of this disease, focusing on recent in vivo and in vitro studies in this field. Initiation and progression of PBC is believed to be a multifactorial process with strong infuences from the patient's genetic background and by various environmental factors. The role of innate and adaptive immunity, including cytokines, chemokines, macrophages and the involvement of apoptosis and reactive oxygen species are outlined in detailed. The current pathogenetic aspects are presented and a novel pathogenetic theory unifying the accumulated clinical information with in vitro and in vivo data is formulated. A review of clinical manifestations and immunological and pathological diagnosis was presented. Treatment modalities, including the multiple mechanisms of action of ursodeoxycholate were finally discussed. PMID- 26261740 TI - Total Wrist Arthroplasty for Posttraumatic Arthritis with Radius Deformity. AB - Newer implant designs and expanding experience have led to a gradual increase in the use of total wrist arthroplasty (TWA) for the treatment of posttraumatic arthritis. New challenges, however, may be encountered with this application, including bony deformities, previous or existing hardware, osteonecrosis, soft tissue injuries, and severe joint stiffness. Because the goals-to relieve pain and provide a functional range of motion-are the same as for more common TWA indications, these technical challenges, along with often higher patient expectations, are important considerations. This article presents possible solutions to these unique surgical challenges, including important preoperative planning to mitigate risks, and the expected outcomes in these patients. PMID- 26261742 TI - Scaphocapitate Fracture: Two Cases with Follow-Up over 5 Years. AB - Background Combined scaphoid and capitate fractures of the wrist are rare entities, and delayed diagnosis is frequent. Scaphocapitate fractures may be associated with reversal of the capitate head 90 degrees or 180 degrees (Fenton syndrome). Different treatment options have been proposed, with variable results. Case Description We report two cases of scaphocapitate fractures of the wrist, diagnosed 3 and 15 days after the injury. The first patient suffered from Fenton syndrome, a combined displaced fracture of the waist of the scaphoid with 180 degrees reversal of capitate head. The second patient had combined fractures of the scaphoid, capitate, and distal radius. In both our cases, anatomic reduction and internal fixation were achieved, resulting in union of all fractures. The long-term results, after 5.5 and 7 years respectively, were very satisfactory, both clinically and radiographically, without signs of avascular necrosis of the head of the capitate or the scaphoid. Literature Review Few reports of scaphocapitate fractures were found in literature. Mechanism of injury, treatment, and outcomes of the reported cases in correlation to our cases are discussed. Clinical Relevance Given the high rate of complications of scaphocapitate fractures, long-term follow-up is important to assess the natural history of the wrist joint after such injuries. The restoration of normal anatomic relationships can lead to a successful long-term functional outcome despite the severity of the injury. PMID- 26261741 TI - Hemiarthroplasty for Complex Distal Radius Fractures in Elderly Patients. AB - Background In elderly patients, distal radius fractures frequently occur in osteoporotic bone and may be nonreconstructable. It is our hypothesis that a hemiarthroplasty replacment of the articular surface can provide satisfactory results in terms of range of motion, pain, and function for immediate salvage of a fracture that is not amenable to internal fixation. Methods Between July 2009 and January 2012, eight elderly patients were treated with insertion of a Sophia distal radius implant (Biotech, Paris, France). Inclusion criteria consisted of an isolated AO type C2 distal radius fracture in patients over 70 years old. All patients were reviewed by an independent surgeon. Results The mean follow-up was 25 months (range, 17-36 months). Mean wrist range of motion (ROM) was 45 degrees (40-50 degrees ) of flexion, 44 degrees (40-50 degrees ) of extension, and a mean pronation-supination arc of 160 degrees . Mean grip force was 18 kgf. The mean QuickDASH (Disabilities of the Arm, Shoulder and Hand) was 18.2/100 (6.82 29.55), and the mean visual analog scale (VAS) was 2.33 (0-4). X-ray images did not demonstrate implant loosening or ulnar translation of the carpus. Conclusions The Sophia hemiarthroplasty provided rapid recovery of independence in elderly patients with a nonreconstructable comminuted distal radius fracture. PMID- 26261743 TI - Management of a Complex, Multioperated Intra-Articular Distal Radius Fracture. AB - Background Intra-articular distal radius fractures can have many complications, including radiocarpal osteoarthritis and distal radioulnar joint (DRUJ) dysfunction leading to pain and restricted wrist function. Case Description We describe the case of a 38-year-old patient who sustained a left distal radius intra-articular fracture, which was treated with volar plating. She developed pain from the radiocarpal joint as a result of intra-articular malunion and was listed for total wrist fusion. On the day of surgery this was converted to a Darrach procedure for minor DRUJ symptoms. This resulted in pain from the DRUJ as a result of instability, in addition to persisting radiocarpal arthritis pain. Due to her subsequent poor wrist function, she presented to the authors and underwent DRUJ arthroplasty with a proximally placed Scheker prosthesis to deal with her DRUJ symptoms and, later, a KinematX radiocarpal hemiarthroplasty for her radiocarpal symptoms. She remains happy with her outcome at 36-month follow up. Literature Review The complications of the Darrach procedure include painful radioulnar convergence and wrist instability. The Scheker prosthesis allows restoration of stability of the DRUJ with good outcomes and 100% 5-year survival in one series. Sparing the midcarpal joint, the KinematX hemiarthroplasty allows preservation of the dart thrower's motion arc, which is key in many complex wrist movements and functions. Clinical Relevance This case highlights the negative consequences of distal ulna resection and shows both the Scheker and KinematX prostheses as viable, effective means to restore function to young, active patients with posttraumatic radiocarpal arthritis and/or instability. PMID- 26261744 TI - The Pronator Quadratus and Distal Anterior Interosseous Nerve: A Cadaveric Study. AB - Background The pronator quadratus (PQ) muscle is an important and commonly encountered structure in surgery of the wrist. A thorough understanding of the anatomy of the PQ and the anterior interosseous nerve (AIN), which innervates the PQ, is important, particularly during distal radius fracture osteosynthesis and distal AIN transfer to deep branch of the ulnar nerve. Furthermore, there is a paucity of literature regarding sex differences in the morphology of these structures. We describe the morphology of the PQ and AIN and compare PQ and AIN findings in male and female specimens. Methods Twenty-five cadaveric upper extremities underwent loupe-aided dissection of the volar forearm with identification of the AIN and PQ. A digital photograph taken perpendicular to the volar surface of the forearm was used to measure the PQ and assess AIN morphology using ImageJ (National Institutes of Health; Bethesda, MD). Comparisons between male and female specimens were performed. Results Of the 25 specimens, 84% appeared as a single trapezoidal muscle bundle, with the remaining 16% demonstrating a double-bundle morphology. The PQ was a mean 3.8 +/- 0.5 cm in radial-ulnar width and 4.6 +/- 0.7 cm in proximal-distal length with a mean thickness, area, and volume of 0.6 +/- 0.2 cm, 18.2 +/- 4.8 cm(2), and 10.5 +/- 3.7 cm(3), respectively. The PQ branch of the AIN was a mean 3.8 +/- 1.1 cm long and had a mean diameter of 1.4 +/- 0.2 mm. Male specimens demonstrated significantly greater radial-ulnar width (p = 0.005), area (p = 0.006), and volume (p = 0.033) of the PQ, as well as a greater distance from the radial styloid to the distal arborization of the AIN (p = 0.005) compared with female specimens. Conclusions The current study informs hand surgeons of the morphologic variability and sexual dimorphism of the PQ and AIN and may help guide operative planning. PMID- 26261745 TI - Anatomic Considerations for Plating of the Distal Ulna. AB - Purpose The purpose of our study was to examine the anatomy of the distal ulna and identify an interval that would be amenable to plating and would not cause impingement during wrist rotation nor irritation to the extensor carpi ulnaris (ECU) tendon. Methods Six cadaveric forearms were dissected and the arc of the articular surface of the distal ulna was measured. The distal ulna was divided up as a clock face, with the ulnar styloid being assigned the 12 o'clock position, and the location of the ECU was identified accordingly. The distance from the ulnar styloid to where the dorsal sensory ulnar nerve crosses from volar to dorsal was also measured. Based on these measurements a safe zone was defined. Results A safe zone was identified between the 12 and 2 o'clock position on the right wrist, and between the 10 and 12 o'clock on the left wrist. The dorsal sensory branch of the ulnar nerve crossed from volar to dorsal position at a variable location near the ulnar styloid. Two commercially available plates were utilized and could be placed in our designated interval and did not cause impingement when the forearm was rotated fully. Conclusion Our study demonstrates a location for plating of the distal ulna that avoids impingement during forearm rotation and that is outside of the footprint of the ECU subsheath. Clinical Relevance Plating of the distal ulna may be necessary with distal ulna fracture, and although plate placement may be dictated by the fracture pattern, it is important to understand the implications of plate placement. Although the ideal plate may not be possible because of comminution, the patient can be educated in regards to potential for tendon irritation, loss of motion, or need for hardware removal. PMID- 26261746 TI - Treatment of Scaphoid Waist Nonunion Using Olecranon Bone Graft and Stryker Asnis Micro Cannulated Screw: A Retrospective Study-80 Case Studies and 6 Years of Follow-Up. AB - Background Screw fixation and bone grafting are the gold standard for scaphoid waist nonunion without avascular necrosis. Question/Purpose Assesses the scaphoid waist nonunion healing rate with use of an uncommon cancellous bone graft (olecranon) and an unusual fixation system (Asnis Micro Cannulated Screw System; Stryker Inc., Kalamazoo, MI, USA). Material and Methods A series of 102 consecutive patients were treated for scaphoid waist nonunion (without deformity). Of these, 80 patients subjected to clinical (Modified Mayo Wrist Score (MMWS), Jamar hydraulic dynamometer) and radiographic examination before and after surgery were evaluated. Ipsilateral olecranon cancellous bone graft and the ASNIS Micro 3.0-mm diameter screw, were used. The average follow up was 6 years (min 3; max 10). Results Radiographic consolidation was achieved in 90% of patients; dorsal intercalated segment instability (DISI) deformities were corrected in 71.4% of cases. Ninety percent improved the range of motion of the wrist and grip strength. All patients showed a significant reduction of peak force in the operated hand. In 6.25% we observed clinical and radiographic screw head-trapezium impingement. Twenty-six patients developed a degenerative wrist sign. The MMWS yielded 68 optimal, 8 good, and 4 bad results. Conclusions To treat scaphoid waist nonunions without misalignment, low-profile headed screw and olecranon bone graft allowed a high consolidation rate with positive results to long-term follow-up. The Asnis Micro 3.0 mm diameter screw may be a suitable option for treating scaphoid waist nonunion. Level of Evidence IV. PMID- 26261747 TI - Pulley Reconstruction As Part of the Surgical Treatment for de Quervain Disease: Surgical Technique with Medium-Term Results. AB - Background Simple decompression of the first extensor compartment is commonly used for treating de Quervain disease, with the possible complication of subluxation of the tendons of the abductor pollicis longus (APL) and extensor pollicis brevis (EPB) over the radial styloid. To prevent this painful subluxation of the tendons, several methods of reconstructing the pulley have been proposed. Questions/Purposes The purpose of our study was to evaluate a new technique for reconstructing the first extensor compartment following a release for de Quervain disease. Patients and Methods A retrospective study (mean length 40.4 months) was performed in 45 patients. The outcome assessment involved two different questionnaires and ultrasound evaluation of any tendon subluxation. Results None of the patients required reoperation for tendon instability or incomplete decompression of the first extensor compartment. Two patients experienced clicking around the radial styloid after surgery. This was not related to the amount of volar migration of the tendons. Conclusions We believe the reconstruction proposed here is an effective method of preventing painful subluxation of the APL and EPB following a release of the first extensor compartment. PMID- 26261748 TI - Is Bone Grafting Necessary in the Treatment of Malunited Distal Radius Fractures? AB - Background Open wedge osteotomy with bone grafting and plate fixation is the standard procedure for the correction of malunited distal radius fractures. Bone grafts are used to increase structural stability and to enhance new bone formation. However, bone grafts are also associated with donor site morbidity, delayed union at bone-graft interfaces, size mismatch between graft and osteotomy defect, and additional operation time. Purpose The goal of this study was to assess bone healing and secondary fracture displacement in the treatment of malunited distal radius fractures without the use of bone grafting. Methods Between January 1993 and December 2013, 132 corrective osteotomies and plate fixations without bone grafting were performed for malunited distal radius fractures. The minimum follow-up time was 12 months. Primary study outcomes were time to complete bone healing and secondary fracture displacement. Preoperative and postoperative radiographs during follow-up were compared with each other, as well as with radiographs of the uninjured side. Results All 132 osteotomies healed. In two cases (1.5%), healing took more than 4 months, but reinterventions were not necessary. No cases of secondary fracture displacement or hardware failure were observed. Significant improvements in all radiographic parameters were shown after corrective osteotomy and plate fixation. Conclusion This study shows that bone grafts are not required for bone healing and prevention of secondary fracture displacement after corrective osteotomy and plate fixation of malunited distal radius fractures. Level of evidence Therapeutic, level IV, case series with no comparison group. PMID- 26261749 TI - Determination of the Central Axis of the Scaphoid. AB - Purpose Determine the central axis of the scaphoid and its relation to surrounding anatomic landmarks to facilitate internal fixation of the scaphoid. Methods Seventeen cadaveric dissections of the wrist were performed. Measurements of the height and width of the proximal pole, waist, and distal pole were made. The midpoint of the height and width of each measurement were plotted on a scatter plot graph and a forecast line was developed. The formula of the resultant line was used to calculate the position of the central axis at the proximal pole, waist, and distal pole. The inverse tangent of the slope of the line was then used to determine the angle of the line from proximal to distal. Results The average central axis fell along a line measuring at points from the ulnar to the radial border and from the dorsal to the volar border of the proximal pole, waist, and distal pole at 7.86 mm, 7.61 mm, and 7.31 mm respectively; an angle of 13.78 degrees from ulnar to radial and dorsal to volar. The proximal point can be determined by measuring ~44 mm radially from the ulnar styloid along the watershed line of the radius and 14 mm volar from the dorsal tip of the Lister tubercle. The distal point can be determined by measuring ~4 mm ulnar from a line extending distally from the volar radial corner, and 7 mm volar from the most dorsal point of the combined surface of the trapezium and triquetrum. No significant difference existed between male and female specimens. Conclusions The central axis of the scaphoid can be described to exist along a line extending from the relative central point of the proximal pole, measured 7.86 mm radial from the scapholunate ligament and 8.31 mm volar of the most dorsal point; through the waist, and extending to the relative central point of the distal pole measured 3.77 mm ulnar of the volar radial corner and 7.36 mm volar of the most dorsal point at an angle directed radially and volarly at 13.78 degrees. Level of Evidence Level III Type of Study Diagnostic/ therapeutic. PMID- 26261750 TI - Distal Oblique Bundle Reinforcement for Treatment of DRUJ Instability. AB - Background Chronic, dynamic bidirectional instability in the distal radioulnar joint (DRUJ) is diagnosed clinically, based on the patient's complaints and the finding of abnormal laxity in the vicinity of the distal ulna. In cases where malunion is ruled out or treated and there are no signs of osteoarthritis, stabilization of the DRUJ may offer relief. To this end, several different techniques have been investigated over the past 90 years. Materials and Methods In this article we outline the procedure for a new technique using a tendon graft to reinforce the distal edge of the interosseous membrane. Description of Technique A percutaneous technique is used to harvest the palmaris longus tendon and to create a tunnel, just proximal to the sigmoid notch, through the ulna and radius in an oblique direction. By overdrilling the radial cortex, the knotted tendon can be pulled through the radius and ulna and the knot blocked at the second radial cortex, creating a strong connection between the radius and ulna at the site of the distal oblique bundle (DOB). The tendon is fixed in the ulna with a small interference screw in full supination, preventing subluxation of the ulna out of the sigmoid notch during rotation. Results Fourteen patients were treated with this novel technique between 2011 and October 2013. The QuickDASH score at 25 months postoperatively (range 16-38 months) showed an improvement of 32 points. Similarly, an improvement of 33 points (67-34 months) was found on the PRWHE. Only one recurrence of chronic, dynamic bidirectional instability in the DRUJ was observed. Conclusion This simple percutaneous tenodesis technique between radius and ulna at the position of the distal edge of the interosseous membrane shows promise in terms of both restoring stability and relieving complaints related to chronic subluxation in the DRUJ. PMID- 26261751 TI - The Impact of Documentation Training on Performance Reporting. AB - With the advent of public reporting of clinical performance for physicians, the need for accurate documentation is essential. This study tested the hypothesis that a short tutorial on five key documentation tips for a group of colorectal surgeons could significantly improve their reported clinical performance. Data was collected on a total of 626 consecutive inpatients before and after the introduction of a short tutorial focusing on five key documentation tips to a group of colorectal surgeons. Quality metrics were compared between the two time periods. Significant improvements were observed for complications (p = 0.001), morbidity (p = 0.046), ileus (p = 0.027), and digestive system complications (p < 0.01). There was no difference in mortality (p = 0.569) or readmissions (p = 0.920). A short tutorial focusing on five key documentation tips is associated with improvement in the reported clinical performance of colorectal surgeons. PMID- 26261752 TI - Central Cord Syndrome in a Young Patient with Early Diffuse Idiopathic Skeletal Hyperostosis and Ossification of the Posterior Longitudinal Ligament after Minor Trauma: A Case Report and Review. AB - This paper is a case report and literature review. The objective of this article is to address a rather unusual case of central cord syndrome in a patient with diffuse idiopathic skeletal hyperostosis and focal ossification of the posterior longitudinal ligament. We also discuss the mechanism of injury in central cord syndrome, as well as that specific to involvement of diffuse idiopathic skeletal hyperostosis (DISH) and ossification of the posterior longitudinal ligament (OPLL). This case took place at SUNY Upstate Medical University. We report a case of a 39-year-old male with early diffuse idiopathic skeletal hyperostosis and focal ossification of the posterior longitudinal ligament, presenting with central cord syndrome after minor trauma. The patient presented with tetraparesis, predominating with significant distal upper extremity weakness and hyperpathia. We performed a C3-6 decompressive laminectomy, with C2 pars screws, and C3-7 lateral mass screws. Since surgery, the patient has had a steady progressive improvement in neurological function and is currently ambulating with a good functional use of his upper extremities. An increased risk of spinal cord injury is a known risk in individuals with pre-existing spinal ankylosing. Few reports are present citing the contribution of focal OPLL with DISH in this age group within the cervical spine contributing to the central cord syndrome. PMID- 26261753 TI - Indices of Regional Brain Atrophy: Formulae and Nomenclature. AB - The pattern of brain atrophy helps to discriminate normal age-related changes from neurodegenerative diseases. Albeit indices of regional brain atrophy have proven to be a parameter useful in the early diagnosis and differential diagnosis of some neurodegenerative diseases, indices of absolute regional atrophy still have some important limitations. We propose using indices of relative atrophy for representing how the volume of a given region of interest (ROI) changes over time in comparison to changes in global brain measures over the same time. A second problem in morphometric studies is terminology. There is a lack of systematization naming indices and the same measure can be named with different terms by different research groups or imaging softwares. This limits the understanding and discussion of studies. In this technological report, we provide a general description on how to compute indices of absolute and relative regional brain atrophy and propose a standardized nomenclature. PMID- 26261754 TI - Small Cell Cancer of the Bladder and Prostate: A Retrospective Review from a Tertiary Cancer Center. AB - BACKGROUND: Genitourinary small cell cancer (GUSCC) is a rare malignancy. Most of the published data on how to manage this malignancy is based on institutional experience. We undertook the current retrospective review to determine the outcome of the patients with GUSCC treated at CancerCare Manitoba, Canada over a period of 18 years. METHODS: The Manitoba Cancer Registry was used to identify patients with a confirmed pathological diagnosis of small cell cancer (SCC) of the bladder or prostate between January 1, 1995, and October 31, 2013. RESULTS: There were 42 patients identified, 28 bladder SCC (17 limited, 11 extensive stage) and 14 prostate SCC (one limited, 12 extensive, and one unknown stage). The median age was 70.7 years. There were 22 patients who were treated with chemotherapy and radiation, five received radiation only, four received chemo only, nine did not receive any treatment, one patient had surgery only, and one had surgery and radiation. The median and one-year overall survival for all patients was 10.7 months and 43%. The median and one-year overall survival of SCC of the bladder was 55.1 months and 71% for the limited stage and 10.1 months and 36% for the extensive stage. The median and one-year overall survival for extensive stage SCC of the prostate was 4.1 months and 17%. There was only one patient with limited stage SCC of the prostate who did not receive any treatment and died of progressive disease 11 months from diagnosis. CONCLUSIONS: Our findings suggest that patients with limited stage SCC of the bladder can have a surprisingly good outcome with multimodality treatment. The outcome of the patients with extensive stage SCC of the bladder and prostate remains dismal and optimal therapeutic options have yet to be determined. PMID- 26261755 TI - Low back pain and patient-reported QOL outcomes in patients with adolescent idiopathic scoliosis without corrective surgery. AB - PURPOSE: To reveal the prevalence of low back pain (LBP) and association between LBP and patient-reported QOL outcomes (JOABPEQ and SRS-22r) in patients with adolescent idiopathic scoliosis (AIS) without corrective surgery. METHODS: Ninety eight female patients with AIS without corrective surgery who answered JOABPEQ, SRS-22r, and VAS for LBP were included. The scores of all subdomains in JOABPEQ and SRS-22r were calculated. From the standing radiographs, we measured the Risser grade and radiographic parameters regarding the curve magnitude, coronal and sagittal balance, and spinopelvic alignment. Furthermore, we recorded whether the patients were undergoing brace treatment at the time of visiting our outpatient clinic. The patients with VAS >30 mm (moderate or severe LBP) were designated as Group P; VAS <=30 mm, Group N. All variables were compared between the groups. RESULTS: The prevalence of LBP (VAS >0 mm) was 34.7% and that of moderate or severe LBP was 16.2%. All subdomain scores in JOABPEQ and those for function and pain in SRS-22r were significantly smaller in Group P than Group N. The subdomain scores for self-image and satisfaction/dissatisfaction with management in SRS-22r did not differ between the groups. The age, Risser grade, radiographic parameters, and whether the patients were undergoing brace treatment did not differ between the groups. CONCLUSIONS: The prevalence of LBP was 34.7%, which was approximately three times higher than that previously reported in Japanese pupils without scoliosis. The patients with LBP demonstrated poorer QOL outcomes associated with LBP regardless of radiographic parameters, patients' self-image and satisfaction with treatment. PMID- 26261756 TI - Effects of different stocking densities on performance and activity of cattle * yak hybrids along a transhumance route in the Eastern Himalaya. AB - Twelve lactating cattle * yak hybrids (B. taurus * B. grunniens) were investigated on five experimental pastures (Sites 1-5), following an up- and downward transhumance route (3,200, 4,000, 4,500, 4,000 and 2,600 m a.s.l.). Hybrids were kept in replicated groups of two (low SD) and four animals per paddock (high SD). As a control, yaks (with calves) were included at low SD at Sites 2-4. Performance was described by body weight, milk yield and composition. Herbage samples as selected by the animals were analyzed. Activity patterns of the hybrids were assessed at Sites 2-4. At similar body weight change and milk composition, the individual hybrids on average produced 26% less milk at high than at low SD. However, at high SD on average still 49% more milk/m(2) of pasture area was produced. Milk fat increased with time from 5.4 to 7.1%, milk protein decreased from 4.2 to 3.3%. At high SD, the hybrids spent less time standing and more time lying. The yaks gained weight at 4,500 m a.s.l. while the hybrids lost weight (+836 and -653 g/animal/day, respectively). In conclusion, high SD reduced individual milk yield and forced hybrids to spend more time for feeding. The yaks apparently had an advantage over the hybrids at very high altitude. PMID- 26261757 TI - A Japanese version of the Pearlin and Schooler's Sense of Mastery Scale. AB - The aims of this research were to develop a Japanese version of Pearlin and Schooler's Sense of Mastery Scale (SOMS) and evaluate its reliability and validity. This survey targeted 4,000 men and women aged 25-74 living in Japan as of January 1, 2014, categorized them according to the region and size of the city in which they lived, randomly extracted 200 municipalities, and randomly extracted individuals after categorizing for sex and age based on the resident registries of each municipality. 2,067 survey responses were collected (response rate 51.7%). We used weighted 7-item (SOMS-7) and 5-item (SOMS-5) versions that excludes two reverse items (item6 and 7) from SOMS-7 of the SOMS. From the item analysis, the item-total correlation coefficients of the two reverse items (items 6 and 7) were .03 and .34. The Cronbach's alpha coefficient was also .69 in SOM-7 and .77 in SOMS-5. The partial correlation coefficients between SOMS and the sense of coherence, mental health inventory, self-rated health, and life satisfaction were all significant (p < 0.001). The SOMS showed high construct validity. SOMS-5 has sufficient reliability. PMID- 26261758 TI - SOX3 expression in the glial system of the developing and adult mouse cerebellum. AB - BACKGROUND: The cerebellum plays a vital role in equilibrium, motor control, and motor learning. The discrete neural and glial fates of cerebellar cells are determined by the molecular specifications (e.g. transcription factors) of neuroprogenitor cells that are influenced by local microenvironment signals. In this study, we evaluated the expression and function of Sox3, a single-exon gene located on the X chromosome, in the developing cerebellum. RESULT: In the embryonic and early postnatal cerebellum, SOX3-positive-cells were detected in the ventricular zone, indicating that SOX3 expression is present in a subset of the cerebellar precursor cell population. In the young adult cerebellum, this expression was diminished in cerebellar cells, suggesting its limited role in cerebellar progenitors. SOX3-positive-cells were also found in the cerebellar mantle zone. Further immunohistochemistry analyses revealed that SOX3 was not expressed in Purkinje neurons. Using glial markers in the early postnatal cerebellum, we found that virtually all of the SOX3-positive-cells were glial cells, although not all glial cells were SOX3-positive-cells. We also determined the impact of transgenic expression using a loss-of-function (Sox3 null) model. We did not observe any developmental defects in the cerebellum of the Sox3 null mice. CONCLUSIONS: Our results indicate that the SOX3 protein is not expressed in cerebellar neurons and is instead expressed exclusively in the cerebellar glial system in a subset of mature glial cells. Although the expression of Sox3 cerebellar glial development is lineage-restricted, it appears that the absence of Sox3 in the ventricular germinal epithelium and migrating glia does not affect cerebellar development, suggesting functional redundancy with other SoxB1 subgroup genes. PMID- 26261759 TI - Anterior urethra sparing cystoprostatectomy for bladder cancer: a 10-year, single center experience. AB - PURPOSE: Decision making regarding the urethra before and after radical cystectomy due to urothelial carcinoma has always been controversial. To determine whether anterior urethra sparing cystoprostatectomy for bladder cancer is an oncologically-safe procedure, we evaluated the long-term oncologic clinical outcome. PATIENTS AND METHODS: A total of 51 male patients with cTa-4N0-2M0 bladder cancer were treated with anterior urethra sparing cystoprostatectomy and simultaneous urinary diversion between 2000 and 2013, and underwent follow up for 4 months or more. We assessed differences in the perioperative outcomes, oncologic outcomes and recurrence rates according to the urinary diversion. RESULTS: The median patient age and follow-up period were 66 years and 35 months, respectively. The 5- and 10-year recurrence free survival (RFS) rates in ileal conduit (IC) group vs. orthotopic neobladder reconstruction (NB) group were 45.0 and 20.3% vs. 39.3 and 19.6%, respectively. Likewise, the 5- and 10-year disease specific survival (DSS) were 52.7 and 32.1% vs. 39.3 and 29.5%, respectively. Multivariate analysis revealed two independent prognostic factors for RFS and DSS, including age at surgery and lymph node status. Local recurrence in the remnant anterior urethra occurred in only 1 patient (2.0%) at 57 months after surgery. CONCLUSIONS: Our long-term data show that anterior urethra sparing cystoprostatectomy is an oncologically-safe procedure regardless of the type of urinary diversion in a subset of carefully selected patients with bladder cancer without evidence of urothelial carcinoma in the urethra/bladder neck and urethral surgical margin. PMID- 26261760 TI - Specific characterization of regional storage fat in upper and lower limbs of young healthy adults. AB - This study aimed to determine the specific characterization of regional storage fat in the upper limb as compared to the lower limb of young healthy adults. The regional storage fat and skeletal muscle in upper and lower limbs were obtained by magnetic resonance imaging (MRI) and multifrequency bioelectrical impedance analysis (BIA). For MRI measurements, images at the continuous anatomical cross sectional areas of subcutaneous adipose tissue and skeletal muscle in the upper arm and thigh were selected for the analysis. Values measured by MRI were larger than those measured by BIA. MRI data showed that the percentage of fat was significantly higher in the upper arm compared to the thigh in both men and women. This study suggests that BIA results in a significantly different estimation of the whole body and limb composition when compared to MRI and that MRI is useful to determine regional specificities in the limb composition. From these quantified evaluation, we found significantly large amount of regional storage fat in upper limbs of young healthy adults, especially women. PMID- 26261761 TI - Assessing drivers of export orientation in the subsea oil and gas industry. AB - The purpose of this short study was to identify the drivers of export orientation of firms in the subsea oil and gas industry in Western Norway. As the oil fields in the North Sea are approaching a stage of maturity, gaining knowledge of these drivers is crucial. An online survey was conducted of firms operating in the subsea oil and gas industry in the region. Consistent with previous research, the data reveal that product innovation and a majority share of international ownership increase firms' export rates. The use of instrumental variables indicates that both product innovation and international ownership are causes of subsea petroleum exports. The study moreover finds that subcontractors have a lower rate of direct exports than system providers, but international ownership in particular boosts subcontractors' export rates, probably by decreasing their market dependency on regional system providers. A clear recommendation for managers and stakeholders is that they should encourage foreign investments throughout the value chain. The results of such a strategy appear to be especially positive for subcontractors. PMID- 26261762 TI - In vitro effects of zinc on the cytokine production from peripheral blood mononuclear cells in patients with zinc allergy. AB - Metals, such as nickel, cobalt, chromium and zinc, are ubiquitous in the environment. Systemic reactions, including hand dermatitis and generalized eczematous reactions, can be caused by the dietary ingestion of metals. In this study, we aimed to determine whether the cytokine production from peripheral blood mononuclear cells (PBMCs) obtained from zinc allergy patients can be used as a sensitive marker to investigate zinc-allergic contact dermatitis. The diagnosis of sensitivity to metal was made based on the results of a metal patch test. The PBMCs were stimulated with various concentrations (5-100 MUM) of zinc sulfate (ZnSO4) for 24 h. The culture supernatants were collected and analyzed using ELISA for measurement of the cytokine production. The levels of IFN-gamma, TNF-alpha, IL-1beta, IL-5, IL-13 and MIF were significantly higher in the zinc allergic patients (n = 5) than in the healthy controls (n = 5) at 100 MUM of ZnSO4 stimulation. Although, patch testing is considered as standard test to diagnose metal allergy but false-positive and -negative reactions may limit its use in conditions of existing dermatitis. Therefore, this study suggest that in support of patch testing the determination of cytokine production using PBMCs cultures would be helpful for making an early diagnosis of such conditions. PMID- 26261763 TI - Limited brain magnetic resonance imaging for evaluation of non-traumatic pediatric head emergencies. AB - Limited brain magnetic resonance imaging (MRI) consisting of axial fluid attenuated inversion recovery, axial diffusion weighted imaging, coronal single shot fast spin echo (SSFSE) and sagittal SSFSE can be performed in under 5 min of scan time. This approach may provide more information than a non-contrast head computed tomography (CT) in non-traumatic pediatric head emergency, avoid ionizing radiation from CT scan and stratify patients who need more detailed brain MRI. Research studies are required to provide evidence for feasibility of such an approach. PMID- 26261764 TI - Blunted perception of dyspnea in asthmatic children: A potential misleading criterion. AB - Dyspnea (or breathlessness) is a symptom describing a perceived experience of breathing discomfort. Children's awareness of dyspnea is variable and there is only a poor correlation between the objective respiratory distress measurements and the subjectively awareness of dyspnea. Those who do not perceive dyspnea may not be motivated to comply with their daily prophylactic treatment. Since dyspnea is the main symptom of asthma, and disease management is based largely on the description of symptoms between clinic visits, unreliable symptom report may mislead decision-making for long-term treatment of asthma. Thus, therapeutic decisions should not be taken solely on patients' perception and description of dyspnea. PMID- 26261765 TI - Prevention of neural tube defects with folic acid: The Chinese experience. AB - Neural tube defects (NTDs) are a group of congenital malformations of the central nervous system that are caused by the closure failure of the embryonic neural tube by the 28(th) day of conception. Anencephaly and spina bifida are the two major subtypes. Fetuses with anencephaly are often stillborn or electively aborted due to prenatal diagnosis, or they die shortly after birth. Most infants with spina bifida are live-born and, with proper surgical treatment, can survive into adulthood. However, these children often have life-long physical disabilities. China has one of the highest prevalence of NTDs in the world. Inadequate dietary folate intake is believed to be the main cause of the cluster. Unlike many other countries that use staple fortification with folic acid as the public health strategy to prevent NTDs, the Chinese government provides all women who have a rural household registration and who plan to become pregnant with folic acid supplements, free of charge, through a nation-wide program started in 2009. Two to three years after the initiation of the program, the folic acid supplementation rate increased to 85% in the areas of the highest NTD prevalence. The mean plasma folate level of women during early and mid-pregnancy doubled the level before the program was introduced. However, most women began taking folic acid supplements when they knew that they were pregnant. This is too late for the protection of the embryonic neural tube. In a post-program survey of the women who reported folic acid supplementation, less than a quarter of the women began taking supplements prior to pregnancy, indicating that the remaining three quarters of the fetuses remained unprotected during the time of neural tube formation. Therefore, staple food fortification with folic acid should be considered as a priority in the prevention of NTDs. PMID- 26261766 TI - Response of levetiracetam in neonatal seizures. AB - AIM: To review the clinical response to levetiracetam (LEV) in neonatal seizure management in intensive care unit. METHODS: Medical records of neonates who received LEV from January 2009 to August 2014 were reviewed. Their demographic data, clinical characteristics, etiology, seizures, electroencephalograms, response to treatment and outcome were noted. Literature review of use of LEV in neonates were also performed via PubMed and EMBASE with keywords - "neonates", "seizures", "epilepsy" and "LEV" up to Sep 2014 and retrieved the publications. The response rate to LEV was compared. RESULTS: Twelve neonates were identified during the study period. All patients received phenobarbitone loading prior to consideration of LEV. Seven (58%) and nine (75%) achieved seizure freedom 24 h and 72 h after LEV was added, both clinically and electrographically. No serious adverse effects were associated with LEV use. From the literature, there are total 144 neonates reported to have used LEV. The overall results suggested that LEV could control up to 90% of neonatal seizures. CONCLUSION: LEV was found to be relatively safe and efficacious in treating neonatal seizures, but might not work well in the most severe hypoxic ischemic encephalopathy. PMID- 26261767 TI - From bronchiolitis guideline to practice: A critical care perspective. AB - Acute viral bronchiolitis is a leading cause of admission to pediatric intensive care units, but research on the care of these critically ill infants has been limited. Pathology of viral bronchiolitis revealed respiratory obstruction due to intraluminal debris and edema of the airways and vasculature. This and clinical evidence suggest that airway clearance interventions such as hypertonic saline nebulizers and pulmonary toilet devices may be of benefit, particularly in situations of atelectasis associated with bronchiolitis. Research to distinguish an underlying asthma predisposition in wheezing infants with viral bronchiolitis may one day lead to guidance on when to trial bronchodilator therapy. Considering the paucity of critical care research in pediatric viral bronchiolitis, intensive care practitioners must substantially rely on individualization of therapies based on bedside clinical assessments. However, with the introduction of new diagnostic and respiratory technologies, our ability to support critically ill infants with acute viral bronchiolitis will continue to advance. PMID- 26261768 TI - Opening the doors of the intensive care unit to cancer patients: A current perspective. AB - The introduction of new treatments for cancer and advances in the intensive care of critically ill cancer patients has improved the prognosis and survival. In recent years, the classical intensive care unit (ICU) admission comorbidity criteria used for this group of patients have been discouraged since the risk factors for death that have been studied, mainly the number and severity of organic failures, allow us to understand the determinants of the prognosis inside the ICU. However, the availability of intensive care resources is dissimilar by country, and these differences are known to alter the indications for admission to critical care setting. Three to five days of ICU management is warranted before making a final decision (ICU trial) to consider keep down intensive management of critically ill cancer patients. Nowadays, taking into account only the diagnosis of cancer to consider ICU admission of patients who need full supporting management is no longer justified. PMID- 26261769 TI - Brain-lung crosstalk: Implications for neurocritical care patients. AB - Major pulmonary disorders may occur after brain injuries as ventilator-associated pneumonia, acute respiratory distress syndrome or neurogenic pulmonary edema. They are key points for the management of brain-injured patients because respiratory failure and mechanical ventilation seem to be a risk factor for increased mortality, poor neurological outcome and longer intensive care unit or hospital length of stay. Brain and lung strongly interact via complex pathways from the brain to the lung but also from the lung to the brain. Several hypotheses have been proposed with a particular interest for the recently described "double hit" model. Ventilator setting in brain-injured patients with lung injuries has been poorly studied and intensivists are often fearful to use some parts of protective ventilation in patients with brain injury. This review aims to describe the epidemiology and pathophysiology of lung injuries in brain injured patients, but also the impact of different modalities of mechanical ventilation on the brain in the context of acute brain injury. PMID- 26261771 TI - Postoperative fluid management. AB - Postoperative care units are run by an anesthesiologist or a surgeon, or a team formed of both. Management of postoperative fluid therapy should be done considering both patients' status and intraoperative events. Types of the fluids, amount of the fluid given and timing of the administration are the main topics that determine the fluid management strategy. The main goal of fluid resuscitation is to provide adequate tissue perfusion without harming the patient. The endothelial glycocalyx dysfunction and fluid shift to extracellular compartment should be considered wisely. Fluid management must be done based on patient's body fluid status. Patients who are responsive to fluids can benefit from fluid resuscitation, whereas patients who are not fluid responsive are more likely to suffer complications of over-hydration. Therefore, common use of central venous pressure measurement, which is proved to be inefficient to predict fluid responsiveness, should be avoided. Goal directed strategy is the most rational approach to assess the patient and maintain optimum fluid balance. However, accessible and applicable monitoring tools for determining patient's actual fluid need should be further studied and universalized. The debate around colloids and crystalloids should also be considered with goal directed therapies. Advantages and disadvantages of each solution must be evaluated with the patient's specific condition. PMID- 26261770 TI - Inhaled hypertonic saline for cystic fibrosis: Reviewing the potential evidence for modulation of neutrophil signalling and function. AB - Cystic fibrosis (CF) is a multisystem disorder with significantly shortened life expectancy. The major cause of mortality and morbidity is lung disease with increasing pulmonary exacerbations and decline in lung function predicting significantly poorer outcomes. The pathogenesis of lung disease in CF is characterised in part by decreased airway surface liquid volume and subsequent failure of normal mucociliary clearance. This leads to accumulation of viscous mucus in the CF airway, providing an ideal environment for bacterial pathogens to grow and colonise, propagating airway inflammation in CF. The use of nebulised hypertonic saline (HTS) treatments has been shown to improve mucus clearance in CF and impact positively upon exacerbations, quality of life, and lung function. Several mechanisms of HTS likely improve outcome, resulting in clinically relevant enhancement in disease parameters related to increase in mucociliary clearance. There is increasing evidence to suggest that HTS is also beneficial through its anti-inflammatory properties and its ability to reduce bacterial activity and biofilm formation. This review will first describe the use of HTS in treatment of CF focusing on its efficacy and tolerability. The emphasis will then change to the potential benefits of aerosolized HTS for the attenuation of receptor mediated neutrophil functions, including down-regulation of oxidative burst activity, adhesion molecule expression, and the suppression of neutrophil degranulation of proteolytic enzymes. PMID- 26261772 TI - Heparin induced thrombocytopenia in critically ill: Diagnostic dilemmas and management conundrums. AB - Thrombocytopenia is often noted in critically ill patients. While there are many reasons for thrombocytopenia, the use of heparin and its derivatives is increasingly noted to be associated with thrombocytopenia. Heparin induced thrombocytopenia syndrome (HITS) is a distinct entity that is characterised by the occurrence of thrombocytopenia in conjunction with thrombotic manifestations after exposure to unfractionated heparin or low molecular weight heparin. HITS is an immunologic disorder mediated by antibodies to heparin-platelet factor 4 (PF4) complex. HITS is an uncommon cause of thrombocytopenia. Reported incidence of HITS in patients exposed to heparin varies from 0.2% to up to 5%. HITS is rare in ICU populations, with estimates varying from 0.39%-0.48%. It is a complex problem which may cause diagnostic dilemmas and management conundrum. The diagnosis of HITS centers around detection of antibodies against PF4-heparin complexes. Immunoassays performed by most pathology laboratories detect the presence of antibodies, but do not reveal whether the antibodies are pathological. Platelet activation assays demonstrate the presence of clinically relevant antibodies, but only a minority of laboratories conduct them. Several anticoagulants are used in management of HITS. In this review we discuss the incidence, pathogenesis, diagnosis and management of HITS. PMID- 26261774 TI - Myeloproliferative and thrombotic burden and treatment outcome of thrombocythemia and polycythemia patients. AB - Prospective studies indicate that the risk of microvascular and major thrombosis in untreated thrombocythemia in various myeloproliferative neoplasms (MPN-T) is not age dependent and causally related to platelet-mediated thrombosis in early, intermediate and advanced stages of thrombocythemia in MPN-T. If left untreated both microvascular and major thrombosis frequently do occur in MPN-T, but can easily be cured and prevented by low dose aspirin as platelet counts are above 350 * 10(9)/L. The thrombotic risk stratification in the retrospective Bergamo study has been performed in 100 essential thrombocythemia (ET) patients not treated with aspirin thereby overlooking the discovery in 1985 of aspirin responsive platelet-mediated arteriolar and arterial thrombotic tendency in MPN-T disease of ET and polycythemia vera (PV) patients. The Bergamo definition of high thrombotic risk and its persistence in the 2012 International Prognostic Score for ET is based on statistic mystification and not applicable for low and intermediate MPN-T disease burden in ET and PV patients on aspirin. With the advent of molecular screening of MPN patients, MPN-T disease associated with significant leukocytosis, thrombocytosis, constitutional symptoms and/or moderate splenomegaly are candidates for low dose peglyated interferon (Pegasys(R), 45 MUg/mL once per week or every two weeks) as the first line myeloreductive treatment option in JAK2(V617F) mutated MPN-T disease in ET and PV patients. If non-responsive to or side effects induced by IFN, hydroxyurea is the second line myelosuppressive treatment option in JAK2(V617F) mutated ET and PV patients with increased MPN-T disease burden. PMID- 26261773 TI - Steps to consider in the approach and management of critically ill patient with spontaneous intracerebral hemorrhage. AB - Spontaneous intracerebral hemorrhage is a type of stroke associated with poor outcomes. Mortality is elevated, especially in the acute phase. From a pathophysiological point of view the bleeding must traverse different stages dominated by the possibility of re-bleeding, edema, intracranial hypertension, inflammation and neurotoxicity due to blood degradation products, mainly hemoglobin and thrombin. Neurological deterioration and death are common in early hours, so it is a true neurological-neurosurgical emergency. Time is brain so that action should be taken fast and accurately. The most significant prognostic factors are level of consciousness, location, volume and ventricular extension of the bleeding. Nihilism and early withdrawal of active therapy undoubtedly influence the final result. Although there are no proven therapeutic measures, treatment should be individualized and guided preferably by pathophysiology. The multidisciplinary teamwork is essential. Results of recently completed studies have birth to promising new strategies. For correct management it's important to establish an orderly and systematic strategy based on clinical stabilization, evaluation and establishment of prognosis, avoiding secondary insults and adoption of specific individualized therapies, including hemostatic therapy and intensive control of elevated blood pressure. Uncertainty continues regarding the role of surgery. PMID- 26261775 TI - Intensive care organisation: Should there be a separate intensive care unit for critically injured patients? AB - In the last two decennia, the mixed population general intensive care unit (ICU) with a "closed format" setting has gained in favour compared to the specialized critical care units with an "open format" setting. However, there are still questions whether surgical patients benefit from a general mixed ICU. Trauma is a significant cause of morbidity and mortality throughout the world. Major or severe trauma requiring immediate surgical intervention and/or intensive care treatment. The role and type of the ICU has received very little attention in the literature when analyzing outcomes from critical injuries. Severely injured patients require the years of experience in complex trauma care that only a surgery/trauma ICU can provide. Should a trauma center have the capability of a separate specialized ICU for trauma patients ("closed format") next to its standard general mixed ICU. PMID- 26261777 TI - Landiolol, an ultra-short-acting beta1-blocker, is useful for managing supraventricular tachyarrhythmias in sepsis. AB - AIM: To investigate whether landiolol, an ultra-short-acting beta1-antagonist, can safely and effectively control heart rate in septic patients with supraventricular tachyarrhythmias. METHODS: We reviewed all patients with sepsis who admitted to our intensive care unit between January 2006 and December 2011. Sixty one septic patients suffered from supraventricular tachyarrhythmias (heart rate >= 120 bpm for > 1 h). Among 61 patients, 39 patients were treated with landiolol (landiolol group) and 22 patients were not treated with landiolol (control group). Arterial pressure, heart rate, cardiac rhythm, pulmonary arterial pressure and cardiac output (if a pulmonary arterial catheter was inserted) were compared between the 2 groups at 1, 8 and 24 h after the initiation of tachyarrhythmias. RESULTS: Mean age and Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were similar between the 2 groups. Paroxysmal atrial fibrillation/flutter (87%), paroxysmal atrial tachycardia (10%), and paroxysmal supraventricular tachycardia (3%) were observed. The initial landiolol dose administered was 6.3 +/- 5.8 g/kg per minute. Rapid and substantial reduction of heart rate was observed in the landiolol group without any deterioration of hemodynamics. Landiolol significantly reduced heart rate (from 145 +/- 14 bpm to 90 +/- 20 bpm) compared to the control group (from 136 +/- 21 bpm to 109 +/- 18 bpm, P < 0.05). The conversion to sinus rhythm was observed more frequently in the landiolol group than in the control group at every point (P < 0.01 at 8 h; P < 0.05 at 1 and 24 h). CONCLUSION: Landiolol safely reduced heart rate and, in part, converted to sinus rhythm in septic patients with supraventricular tachyarrhythmias. PMID- 26261776 TI - Severe scrub typhus infection: Clinical features, diagnostic challenges and management. AB - Scrub typhus infection is an important cause of acute undifferentiated fever in South East Asia. The clinical picture is characterized by sudden onset fever with chills and non-specific symptoms that include headache, myalgia, sweating and vomiting. The presence of an eschar, in about half the patients with proven scrub typhus infection and usually seen in the axilla, groin or inguinal region, is characteristic of scrub typhus. Common laboratory findings are elevated liver transaminases, thrombocytopenia and leukocytosis. About a third of patients admitted to hospital with scrub typhus infection have evidence of organ dysfunction that may include respiratory failure, circulatory shock, mild renal or hepatic dysfunction, central nervous system involvement or hematological abnormalities. Since the symptoms and signs are non-specific and resemble other tropical infections like malaria, enteric fever, dengue or leptospirosis, appropriate laboratory tests are necessary to confirm diagnosis. Serological assays are the mainstay of diagnosis as they are easy to perform; the reference test is the indirect immunofluorescence assay (IFA) for the detection of IgM antibodies. However in clinical practice, the enzyme-linked immuno-sorbent assay is done due to the ease of performing this test and a good sensitivity and sensitivity when compared with the IFA. Paired samples, obtained at least two weeks apart, demonstrating a >= 4 fold rise in titre, is necessary for confirmation of serologic diagnosis. The mainstay of treatment is the tetracycline group of antibiotics or chloramphenicol although macrolides are used alternatively. In mild cases, recovery is complete. In severe cases with multi organ failure, mortality may be as high as 24%. PMID- 26261778 TI - Outcomes of critically ill cancer patients with Acinetobacter baumannii infection. AB - AIM: To describe the intensive care unit (ICU) outcomes of critically ill cancer patients with Acinetobacter baumannii (AB) infection. METHODS: This was an observational study that included 23 consecutive cancer patients who acquired AB infections during their stay at ICU of the National Cancer Institute of Mexico (INCan), located in Mexico City. Data collection took place between January 2011, and December 2012. Patients who had AB infections before ICU admission, and infections that occurred during the first 2 d of ICU stay were excluded. Data were obtained by reviewing the electronic health record of each patient. This investigation was approved by the Scientific and Ethics Committees at INCan. Because of its observational nature, informed consent of the patients was not required. RESULTS: Throughout the study period, a total of 494 critically ill patients with cancer were admitted to the ICU of the INCan, 23 (4.6%) of whom developed AB infections. Sixteen (60.9%) of these patients had hematologic malignancies. Most frequent reasons for ICU admission were severe sepsis or septic shock (56.2%) and postoperative care (21.7%). The respiratory tract was the most frequent site of AB infection (91.3%). The most common organ dysfunction observed in our group of patients were the respiratory (100%), cardiovascular (100%), hepatic (73.9%) and renal dysfunction (65.2%). The ICU mortality of patients with 3 or less organ system dysfunctions was 11.7% (2/17) compared with 66.6% (4/6) for the group of patients with 4 or more organ system dysfunctions (P = 0.021). Multivariate analysis identified blood lactate levels (BLL) as the only variable independently associated with in-ICU death (OR = 2.59, 95%CI: 1.04-6.43, P = 0.040). ICU and hospital mortality rates were 26.1% and 43.5%, respectively. CONCLUSION: The mortality rate in critically ill patients with both HM, and AB infections who are admitted to the ICU is high. The variable most associated with increased mortality was a BLL >= 2.6 mmol/L in the first day of stay in the ICU. PMID- 26261779 TI - Erratum: MLTJ 1/15: Pilot experimental study on amniotic epithelial mesenchymal cell transplantation in natural occurring tendinopathy in horses. Ultrasonographic and histological comparison. AB - [This corrects the article on p. 5 in vol. 5, PMID: 25878980.]. PMID- 26261780 TI - Retraction. AB - [This retracts the article on p. 471 in vol. 4, PMID: 25767786.][This retracts the article on p. 471 in vol. 4, PMID: 25767786.]. PMID- 26261781 TI - Publish and perish. Publish and be damned. Caveat the Author. PMID- 26261782 TI - Quantitative bi-component T2* analysis of histologically normal Achilles tendons. AB - INTRODUCTION: the aim of this pilot study was to implement ultrashort echo time (UTE) MRI with bi-component analysis on grossly normal Achilles tendons with histologic correlation. MATERIALS AND METHODS: six tendon samples which were grossly normal on visual inspection and palpation were harvested. A 2D UTE pulse sequence was implemented on a 3T MR scanner and bi-component and single-component T2* analysis was performed. Tendon samples were histologically processed and evaluated. RESULTS: mean short T2* fraction was 79.2% (95% confidence interval [CI], 70.1 - 88.3%), mean short T2* was 1.8 ms (95% CI, 1.3 - 2.3 ms), mean long T2* fraction was 20.8% (95% CI, 11.7 - 29.9%), mean long T2* was 9.2 ms (95% CI, 5.1 - 13.3 ms), and mean single-component T2* was 2.5 ms (95% CI, 1.8 - 3.1 ms). DISCUSSION: 2D UTE MRI with bi-component and single-component T2* analysis was successfully implemented. Inter-individual variation can be demonstrated in grossly and histologically normal Achilles tendons. PMID- 26261783 TI - Influence of a lower leg brace on traction force in healthy and ruptured Achilles tendons. AB - BACKGROUND: we investigated how ruptured Achilles tendons are loaded in a brace. There is an ongoing discussion whether patients should be recommended to bear weight on the injured limb. However, little is known about the effects of bracing on tensional loading of the healing Achilles tendon: it is uncertain if load bearing actually stresses the Achilles tendon inside a brace. METHODS: we measured plantar flexion moment inside the brace, in order to estimate tensional loading of the tendon, by use of an insole with pressure transducers. RESULTS: after wearing the brace for 1 hour, young healthy individuals reduced their maximum flexion moment during gait by half. Patients with Achilles tendon rupture showed no measurable flexion moment during gait with the brace, 4 or 7 weeks after injury. Only when specifically instructed, they could produce a considerable plantar flexion moment. We noted that gait speed with the brace at 4 weeks correlated with a heel-raise functional test at 1 year: the higher the spontaneous gait speed, the less the functional difference between the injured and the uninjured leg (r(2)=0.68; p=0.002). CONCLUSION: the correlation with gait speed suggests that the patients' general physical aptness has an impact on the end result. PMID- 26261784 TI - Clinical assessment is sufficient to allow outcome evaluation following surgical management of Achilles tendon ruptures. AB - STUDY DESIGN: cross-sectional study in otherwise healthy athletic adults with a unilateral Achilles tendon rupture. OBJECTIVES: define the relationships of active range of motion, calf circumference or number of heel raises to a full set of isokinetic parameters. BACKGROUND: Achilles tendon ruptures commonly occur during sports and create a considerable amount of morbidity. The benefits of different treatments are difficult to determine. Complex and expensive isokinetic testing is often required. If a simple force measurement could replace this testing, large clinical trials would be more easily feasible. METHODS: 74 patients with acute Achilles tendon rupture and surgical treatment were evaluated retrospectively. Active range of motion (ROM), ratio of ROM, number of heel raises, ratio of heel raises, calf circumference and isokintetic measurements were recorded. Regression using a Bayesian elastic net showed the most important correlations. RESULTS: Active range of motion showed a significant correlation to peak torque angle at flexion and extension as well as increased sports activity. There was a negative correlation to percutaneous therapy. Active Heel raise showed a positive correlation to peak torque at dorsal extension and increased sports activity as well as a negative correlation to high postoperative pain, where as calf circumference was positive correlated to peak torque at dorsal extension and body height as well as negative correlated to female gender. CONCLUSION: device independent measures, like range of Motion, and amount of Heel raise, are an excellent tool providing similar information compared to isokinetic testing and could be used to evaluate clinical outcome after Achilles tendon rupture. PMID- 26261785 TI - High volume image-guided injections and structured rehabilitation improve greater trochanter pain syndrome in the short and medium term: a combined retrospective and prospective case series. AB - BACKGROUND: the aim of this study was to measure the effects of high volume image guided injections and structured rehabilitation (HVIGI&SR) for greater trochanter pain syndrome (GTPS). METHODS: 31 consecutive subjects were recruited (23 retrospectively; 8 prospectively) over 5 months. GTPS was diagnosed based on history and examination findings, alongside radiological examination. The HVI-GI used a 22-gauge spinal needle to administer 10ml of 0.5% Marcaine and 50 mg hydrocortisone just deep to the periosteum underlying the gluteal tendon insertion under ultrasound guidance, followed by structured rehabilitation. A visual analogue scale (VAS) for pain was used as the main outcome measure. RESULTS: the mean VAS improved from 81.7 mm (+/-17.6) to 42.3 mm (+/-28.3), (p<0.05) in the prospective subjects at a mean of 6 weeks, considered clinically significant. In the retrospective subjects the mean VAS had improved from 74.6 (+/-10.9) mm to 38.2(+/-31.2) mm at two weeks (p<0.01) and 31.3 (+/-27.6) mm at the final time point, a mean of 60 weeks (p<0.01). The Hip and Groin Outcome Score in the prospective group showed a non-significant increase from 173.2 to 296.1 (p=0.12). CONCLUSION: HVIGI&SR should be considered when short- and medium term pain-relieving treatment for GTPS is required. Controlled studies are warranted to fully establish effectiveness, and assess long term effects. LEVEL OF EVIDENCE: case series. PMID- 26261786 TI - Association between patella spurs and quadriceps tendon ruptures. AB - BACKGROUND: quadriceps tendon (QT) ruptures are significant injuries that are relatively uncommon. The diagnosis of QT ruptures is frequently missed or delayed. An association between the presence of a patella spur and QT ruptures has been suggested in the literature. PATIENTS AND METHODS: the Hospital Inpatient Enquiry system was used to gather data on all patients who sustained a QT rupture over a six year period from 2008 to 2014. A retrospective review of the medical notes as well as radiographs was undertaken. We reviewed 200 knee radiographs of patients without QT ruptures to establish the incidence of patella spurs in our normal population. Statistical analysis was performed using SPSS version 11.5 for Windows((r)). RESULTS: the records of 20 consecutive patients with 21 QT ruptures were reviewed. The mean age was 60.9 yrs (range 44.9-82.1 yrs) and the majority were male (n=17; 85%). There was one bilateral QT ruptures. Patella spurs were noted in 13 cases (62%) which were significantly higher than in patients without QT rupture 19% (P<=0.05). CONCLUSION: we noted a significantly higher incidence of patella spurs in patients with QT ruptures compared to those without. The presence of a QT rupture should be ruled out in patients with a knee injury and a patella spur on the knee radiographs. PMID- 26261787 TI - Platelet-rich plasma as a treatment for chronic patellar tendinopathy: comparison of a single versus two consecutive injections. AB - BACKGROUND: platelet-rich-plasma is increasingly used in chronic patellar tendinopathy. Ideal number of PRP injections needed is not yet established. This study compares the clinical outcomes of a single versus two consecutive PRP injections. METHOD: between December 2009 and January 2012, 40 athletes with proximal patellar tendinopathy were treated by PRP injection. Patients received single (20 patients) or two PRP injections 2 weeks apart (20 patients). All patients underwent prospective clinical evaluation, including Victorian Institute of Sport Assessment-Patella (VISA-P) score, visual analog scale (VAS) for pain, and Tegner scale before PRP and after a minimum of 2 year follow-up. RESULTS: 9 patients failed PRP treatment and needed surgery. 1 patient was lost to follow up. For the remaining patients, the VISA-P, VAS, and Tegner scores all significantly improved from 35.2 to 78.5 (p = 0.0001), 6.6 to 2.4 (p = 0.0001), and 4.8 to 6.9 (p = 0.0003). Patients who received two injections had better scores than those who received single injection with VAS of 1.07 versus 3.7 (p = 0.0005), Tegner score of 8.1 versus 5.9 (p = 0.0003) and VISA-P of 93.2 versus 65.7 (p = 0.0001). CONCLUSIONS: two consecutive PRP injections in chronic patellar tendinopathy showed better improvement in outcomes when compared to single injection. LEVEL OF EVIDENCE: randomized prospective consecutive series, Level 2. PMID- 26261788 TI - The molecular systemic and local effects of intra-tendinous injection of Platelet Rich Plasma in tendinosis: preliminary results on a rat model with ELISA method. AB - PURPOSE: the aim of our study was thus to quantify the effect of Platelet Rich Plasma (PRP) injection on systemic and local growth factors and to identify molecular markers in a rat model of patellar and Achilles tendinosis treated with PRP. MATERIAL AND METHOD: twenty two rats were used for the study. Two healthy rats were used as control (T-). We induced tendinosis (T+) in 20 rats (80 tendons by injecting under ultrasonography (US) guidance Collagenase 1(r) (day 0 = D0, patellar=40 and Achilles=40). At D3, these 20 rats with tendinosis were separated in treatment by either PRP (PRPT+, n=28), physiological serum (PST+, n=28, control) US-guided intratendinous injection, or without no PRP or PS (T+, n=24, control of natural evolution of tendinopathy). Follow-up at D7, D13, D18 and D25 using serum sample and local tendon removal with ELISA technics and comparison between the 3 groups were performed. RESULTS: during biological follow up, comparison of all serum samples of PRPT+, PST+ and T+ groups showed no significant modification of their biological markers at D7, D13, D18 and D25 (p>0.22). Comparison of immunological sample tendon markers of PRPT+, PST+ and T+ groups also showed no significant modification of markers at D7, D13, D18 and D25 (p>0.16) considering each biological marker and also all subgroups confounded. CONCLUSION: our study strongly suggests that a single intratendinous US-guided injection of PRP in Achilles and patellar T+ doesn't increase biological markers such as growth factors compared to a control group in mid-term and long-term follow-up. PMID- 26261789 TI - Muscle atrophy and fatty infiltration after an acute rotator cuff repair in a sheep model. AB - INTRODUCTION: rotator cuff tears (RCTs) are the most common tendon injury seen in orthopedic patients. Muscle atrophy and fatty infiltration of the muscle are crucial factors that dictate the outcome following rotator cuff surgery. Though less studied in humans, rotator cuff muscle fibrosis has been seen in animal models as well and may influence outcomes as well. The purpose of this study was to determine if the rotator cuff would develop muscle changes even in the setting of an acute repair in a sheep model. We hypothesized that fatty infiltration and fibrosis would be present even after an acute repair six months after initial surgery. METHODS: twelve female adult sheep underwent an acute rotator cuff tear and immediate repair on the right shoulder. The left shoulder served as a control and did not undergo a tear or a repair. Six months following acute rotator cuff repairs, sheep muscles were harvested to study atrophy, fatty infiltration, and fibrosis by histological analysis, western blotting, and reverse transcription polymerase chain reaction (RT-PCR). RESULTS: the repair group demonstrated an increase expression of muscle atrophy, fatty infiltration, and fibrosis related genes. Significantly increased adipocytes, muscle fatty infiltration, and collagen deposition was observed in rotator cuff muscles in the tendon repair group compared to the control group. CONCLUSIONS: rotator cuff muscle undergoes degradation changes including fatty infiltration and fibrosis even after the tendons are repair immediately after rupture. LEVEL OF EVIDENCE: Basic Science Study. PMID- 26261790 TI - Bone morphogenetic protein signaling in rotator cuff muscle atrophy and fatty infiltration. AB - BACKGROUND: reduced mass (atrophy) and increased fat content (fatty infiltration) of rotator cuff muscles are common complications of large or massive rotator cuff (RC) tears, and are believed to be irreversible even after tendon repairs. Clinically, both muscle atrophy and fatty infiltration are important factors contributing to poor functional outcomes after tendon repairs. The molecular mechanism of RC muscle atrophy and FI remains undefined. In this study, we investigated the role of bone morphogenetic proteins (BMP) signaling in RC muscle atrophy and fatty infiltration using a rat model. METHODS: unilateral massive RC tears was induced in adult rats. RC muscles were harvested at 2 and 6 weeks after injury for BMP signaling analysis. In a separate experiment, BMP inhibitor (LDN 193189) was injected to rats through daily intraperitoneal injection. RC muscles from rats in the treated and control groups were harvested at 6 weeks after injury for biochemistry and histology analysis. RESULTS: we found significantly increased BMP-14 and BMP-7 expression in rotator cuff muscles after RCT. Inhibiting BMP signaling resulted in increased muscle atrophy and reduced fatty infiltration in rotator cuff muscle after RC tears. CONCLUSION: this result suggests that BMP signaling inhibits RC muscle atrophy but promotes fatty infiltration. PMID- 26261791 TI - Longitudinal tear of the biceps brachii from peripheral intravenous catheter infiltration. AB - BACKGROUND: although peripheral intravenous catheter (PIV) infiltration is a frequent hospital occurrence, muscle rupture is a previously unknown complication of line infiltration. We present the case of a 21-year-old male with a history of cystic fibrosis, bilateral lung transplant, and chronic corticosteroid use, with longitudinal tear of the biceps brachii muscle as a complication of PIV infiltration. METHODS: case report describing a unique case of a longitudinal tear of the biceps brachii. RESULTS: magnetic resonance imaging revealed longitudinal tear of the biceps brachii with sparing of the proximal and distal tendons. Nerve conduction studies and electromyography revealed bicipital denervation, most likely due to mechanical compression. CONCLUSION: we hypothesize that the patient's chronic corticosteroid use predisposed him to muscle injury, as did basilic vein thrombosis caused by PIV infiltration, and this combination of factors led to bicipital rupture. To our knowledge, this is also the first case report to document longitudinal tear of the biceps brachii with sparing of the distal and proximal tendinous insertions of the muscle. PMID- 26261792 TI - High magnitude, in vitro, biaxial, cyclic tensile strain induces actin depolymerization in tendon cells. AB - BACKGROUND: the cytoskeleton is a dynamic arrangement of actin filaments that maintain cell shape and are vital in mediating the mechanobiological response of the cell. METHODS: to determine the cytoskeletal response to varying in vitro, biaxial stretch amplitudes, rat-tail tendon cells were paired into control and cyclically strained groups of 4.75, 9.5, or 12% strain at 1 Hz for 2 hours and the actin cytoskeleton stained. The cells were analyzed for actin staining intensity as a measure of relative depolymerization and for cell shape. Collagenase gene expression was measured in cells undergoing 12% cyclic strain at 1 Hz for 24 hours. RESULTS: there was no significant difference in the degree of actin staining intensity between the control group and cells strained at either 4.75 or 9.5%. However, cells strained at 12% demonstrated a significant decrease in actin staining intensity (depolymerization) compared to control cells, increased collagenase expression by 81%, and a clear shift towards a more rounded cell shape. CONCLUSION: the results of this study demonstrate that the previously reported induction of collagenase activity associated with the application of high magnitude, in vitro, tensile strains may actually be a result of cytoskeletal depolymerization, which causes loss of tensional homeostasis and alteration of cell shape. PMID- 26261793 TI - Current techniques for management of transverse displaced olecranon fractures. AB - BACKGROUND: displaced transverse fractures of the olecranon are the most common fractures occurring in the elbow in adults that requires operative intervention. METHODS: a literature search was performed on PubMed, Web of Science, Science Direct/Scopus, Google Scholar and Google using the keywords 'olecranon', 'fracture', 'internal fixation' and 'tension band wiring', with no limit for time or restrictions to language. RESULTS: thirty-one clinical articles were selected: 20 retrospective studies, 9 prospective cohort studies, and 2 randomized control trials. The CMS ranged from 18 to 66 (mean 41.68): overall, the quality of the studies was poor, and no moderate or good quality studies were found. The mean follow-up was 46.7 months (range 1 to 350 months). Several complications occurred after surgery: prominent hardware, skin breakdown, wire migration and infections occurred frequently. Removal of the hardware was required in 472 patients, usually after complaints, but also removal was routinely undertaken. CONCLUSIONS: tension band wiring is still the most widely applied method to operatively manage olecranon fractures, with the transcortical method of using K-wires the most satisfactory. Plate fixation is a good alternative as complications are minimal. Other techniques using absorbable sutures are less investigated, but are promising, especially in children. PMID- 26261794 TI - Platelet-rich plasma treatment improves outcomes for chronic proximal hamstring injuries in an athletic population. PMID- 26261795 TI - Author Response. PMID- 26261796 TI - p38 MAPK and PI3K/AKT Signalling Cascades inParkinson's Disease. AB - Parkinson's disease (PD) is a chronic neurodegenerative condition which has the second largest incidence rate among all other neurodegenerative disorders barring Alzheimer's disease (AD). Currently there is no cure and researchers continue to probe the therapeutic prospect in cell cultures and animal models of PD. Out of the several factors contributing to PD prognosis, the role of p38 MAPK (Mitogen activated protein-kinase) and PI3K/AKT signalling module in PD brains is crucial because the impaired balance between the pro- apoptotic and anti-apoptotic pathways trigger unwanted phenotypes such as microglia activation, neuroinflammation, oxidative stress and apoptosis. These factors continue challenging the brain homeostasis in initial stages thereby essentially assisting the dopaminergic (DA) neurons towards progressive degeneration in PD. Neurotherapeutics against PD shall then be targeted against the misregulated accomplices of the p38 and PI3K/AKT cascades. In this review, we have outlined many such established mechanisms involving the p38 MAPK and PI3K/AKT pathways which can offer therapeutic windows for the rectification of aberrant DA neuronal dynamics in PD brains. PMID- 26261797 TI - Association Between MTHFR Genetic Variants and Multiple Sclerosis in a Southern Iranian Population. AB - Multiple sclerosis (MS) is a demyelinating neuro- inflammatory autoimmune disease of the central nervous system. Genetic predisposition has long been suspected in the etiology of this disease. The association between MTHFR polymorphisms and MS has been ivestigated in different ethnic groups. We investigated the association between MTHFR C677T and A1298C missense variants and MS in 180 patients and 231 age- and gender-matched healthy controls in a Southern Iranian population. The mutagenically separated PCR (MS-PCR) and PCR-RFLP methods were used to genotype MTHFR at position 677 and 1298, respectively. Compared with controls, we observed a strong association between two MTHFR variants and the risk of developing MS. Subjects carrying 677T allele (CT and TT genotypes) had increased susceptibility to MS as compared to those carrying CC genotype (odds ratio (OR) for CT= 2.9, 95% confidence interval (95% CI)= 1.88-4.49; OR for TT= 6.23, 95% CI= 3.08-12.59). The variant 1298AC genotype also increased the risk for MS among our study population (OR= 2.14, 95% CI= 1.37-3.34). Combined genotype analysis for two MTHFR SNPs revealed that compared to the wild type genotypes (677CC/1298AA), 3 genotypes including TT/AC, CT/AC, and TT/AA were significantly at increased risk for MS development (OR= 13.9, 5.3, and 4.9, respectively). Our results suggest a possible gene dose- dependent association between MTHFR mutrant alleles and the risk of MS development. PMID- 26261798 TI - Elevation of cAMP Levels Inhibits Doxorubicin-Induced Apoptosis in Pre- B ALL NALM- 6 Cells Through Induction of BAD Phosphorylation and Inhibition of P53 Accumulation. AB - Recognition of the molecular mechanisms of cAMP action against DNA damage-induced apoptosis can be useful to improve the efficacy of DNA damaging therapeutic agents. Considering the critical role of bcl-2-associated death promoter (BAD) and p53 proteins in DNA damage -induced apoptosis, the aim of this study was to assess the effect of cAMP-elevating agents on these proteins in doxorubicin treated pre-B acute lymphoblastic leukemia (pre-B ALL) NALM-6 cells.The pre-B ALL cell line NALM-6 was cultured and treated with doxorubicin in combination with or without cAMP-elevating agents forskolin and 3-isobutyl-1-methylxanthine (IBMX). Cell viability was measured by trypan blue staining and MTT assay. For evaluation of apoptosis, annexin-V staining by flow cytometry and caspase-3 activity assay were used. Protein expression of p53, BAD and phoshorylated BAD was detected by western blotting analysis.cAMP-increasing agents diminished the doxorubicin mediated cytotoxicity in NALM-6 cells as indicated by the viability assays. Annexin-V apoptosis assay showed that the cAMP-elevating agents decreased doxorubicin-induced apoptosis. Moreover, doxorubicin-induced caspase-3 activity was attenuated in the presence of cAMP-increasing agents. Western blot results revealed the reduced expression of p53 protein in cells treated with combination of cAMP-elevating agents and doxorubicin in contrast to cells treated with doxorubicin alone. Expression of total BAD protein was not affected by doxorubicin and cAMP-elevating agents. However, phosphorylation of BAD protein was induced in the presence of cAMP-elevating agents. Our study suggests that elevated cAMP levels inhibit doxorubicin-induced apoptosis in pre-B ALL cells through induction of BAD phosphorylation and abrogation of p53 accumulation. PMID- 26261799 TI - APOBEC3 Deletion is Associated with Breast Cancer Risk in a Sample of Southeast Iranian Population. AB - Breast Cancer (BC) is considered as one of the most important causes of death worldwide. Previous studies showed that apolipoprotein B mRNA- editing catalytic polypeptide-like 3 (APOBEC3) gene deletion significantly increased the risk of BC risk in Chinese and European women. The present study aimed to assess the possible impact of APOBEC3 deletion and the risk of BC in a sample of Iranian population. The APOBEC3 insertion/deletion (I/D) was analyzed in a case- control study including 262 BC patients and 217 healthy women. Polymerase chain reaction (PCR) was used to genotype the variant in APOBEC3 gene. The findings of this study showed that I/D as well as I/D+D/D genotype increased the risk of BC (OR= 1.57, 95% CI= 1.07- 2.31, p= 0.025 and OR= 1.50, 95% CI= 1.03- 2.19, p= 0.037, respectively) in comparison with I/I genotype. In conclusion, our findings suggest that APOBEC3 deletion polymorphism increased the risk of BC in an Iranian population in the southeast of Iran. PMID- 26261800 TI - Expression Pattern of Alternative Splicing Variants of Human Telomerase Reverse Transcriptase (hTERT) in Cancer Cell Lines Was not Associated with the Origin of the Cells. AB - Telomerase and systems controlling their activity have been of great attention. There are controversies regarding the role of the alternative splicing forms of the human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase. Therefore, the correlation between telomerase enzyme activity, the abundance of alternatively spliced variants of hTERT and doubling time of a series of cancer cell lines originated from hematopoietic, breast, colorectal, neural, ovarian, lung, kidney, bladder, prostate and head and neck cancers were investigated. Expression levels of four different variants of hTERT (the full length, alpha-deletion, beta-deletion and alpha/beta-deletion) were quantitatively measured by real time PCR. Telomerase activity was determined by the telomerase repeat amplification protocol (TRAP) while doubling time of the cells measured by plotting growth curves. Results showed high diversity in the relative proportions of hTERT transcripts while the majority of the cells expressed the full length variant as the main transcript. Telomerase activity could not be detected in all cells. Relative assessment of hTERT expression showed greater expression of the alpha-deleted variant in the telomerase negative cells (P= 0.04). Those cells possessed the alpha/beta-deleted variant to a smaller extent when compared to the cells with telomerase activity. Greater association between full length spliced variant and beta-variant expression was observed in cells presenting telomerase activity (P= 0.0007, r= 0.74). High degrees of variation among the studied cells regarding the pattern of hTERT expression were present. In spite that, the regulatory roles of hTERT on telomerase activity is still a potential to be utilized as targets for cancer therapies. PMID- 26261801 TI - Multiple Inherited Thrombophilic Gene Polymorphisms in Spontaneous Abortions in Turkish Population. AB - The aim of this study was to investigate the possible role of multiple inherited thrombophilic gene variations in women with unexplained spontaneous abortions. For this purpose, the Factor V Leiden (FVL) (rs6025), Prothrombin G20210A (rs1799963), MTHFR C677T (rs1801133), PAI-1 4G/5G (rs1799889), ACE I/D (rs1799752), eNOS E298D (rs1799983), and Apo E E2/E3/E4 (rs429358) polymorphisms were genotyped and correlated in spontaneously aborted fetal materials, their mothers and fertile women. Twenty three abortion materials, 22 women with >=1 unexplained fetal loss, and 22 control subjects with at least two healthy term infants as a control group were studied. Target SNPs for each gene were analyzed by real time-PCR technique after genomic DNA isolation from maternal blood-EDTA, control group blood-EDTA and spontaneously aborted fetal tissues. Some cases had a single thrombophilic polymorphism, but the rest of the patients and fetal materials had combined thrombophilic polymorphisms. The PAI-1 4G/5G+4G/4G (P= 0.0017), 4G/4G (P= 0.0253), eNOS 894GT+894TT (P=0.0011) genotypes and T allele (P=0.0185), Apo E E3/E4+E3/E2+E2/E4 (P<0.0001) genotypes, E2 (P<0.0001) and E4 (P<0.0001) alleles were higher in spontaneously aborted fetal materials when compared to their mothers and control group. The Factor V Leiden rs6025, Prothrombin G20210A, MTHFR C677T, ACE I/D genotypes were different for each group but not statistically significant due to relatively small size of the samples (P>0.05). Our results indicated that combined thrombophilic gene variations may be associated with increased risk for spontaneous abortions and results need to be confirmed by larger sample size. PMID- 26261802 TI - Cytotoxic and Antioxidant Activity of a Set of Hetero Bicylic Methylthiadiazole Hydrazones: A Structure-Activity Study. AB - The current study highlights the in vitro antioxidant and antitumor activity of the previously-synthesized hydrazone derivatives against various free radicals and human cancer cell lines, respectively. The anticancer efficacies of the compound were tested by measuring cytotoxicity in cancer cell lines HeLa, A549, and non-cancerous NL20 cells. Compounds possessing electron-donor methoxy and methyl substitutions at the para position of the phenyl ring moiety showed a concentration dependent free radical scavenging effects. The free radical scavenging potential of synthetic compounds 11 and 14 may have significant impact on the prevention of free radical-induced oxidative stress and carcinogenesis. The results from cytotoxicity and cell migration assay showed that the substitution of electron-withdrawing fluoro, chloro and bromo functional groups induced a significant (P< 0.001) loss of cell viability and inhibited the invasive potential of the human cancer cells. Additionally, these compounds showed significantly (P< 0.05) a less toxicity toward non-cancerous NL20 cells. Docking studies revealed interactions of compound 10 with p38alpha MAP kinase, which may be responsible of its anti-invasive and anti-proliferative effects. PMID- 26261804 TI - A study to investigate the importance of purses as fomites. AB - BACKGROUND: Purses hardly get washed and are discarded, mostly, when they are no longer usable. This study aims to investigate whether women's and men's purses can serve as fomites. MATERIALS AND METHODS: A total of 145 purses from 80 women and 65 men were swabbed and cultured. The bacteria were identified by gram staining and with the standard biochemical tests. RESULTS: A total of 138 purses (95.2%) showed bacterial contamination, out of which 49.4% had a single growth and 50.7% had mixed growth. The material of the purse was found to affect bacterial growth. Synthetic purses showed higher mean colony-forming unit (CFU) counts (P < 0.05). Micrococcus (64.8%) and coagulase-negative Staphylococcus (64.1%) were the most common bacteria isolated, followed by Bacillus spp. (13.8%). Micrococcus was found with a higher prevalence on men's purses, while Bacillus spp. were more prominent on women's purses (P < 0.05). The difference between the rates of bacterial growth from the purses of women and of men was found to be statistically significant (57.2% and 44.7%; P < 0.05). Furthermore, the mean CFU count was higher for men's purses than for women's purses (P < 0.05). CONCLUSION: Purses from both men and women are potential vectors for transmission of diseases across the community. The use of synthetic purses should be discouraged, as they contribute to increased bacterial colonization. PMID- 26261803 TI - Virulence Factors Variation Among Bordetella Pertussis Isolates in Iran. PMID- 26261806 TI - Molecular typing of Brucella species isolates from Human and livestock bloods in Isfahan province. AB - BACKGROUND: Human brucellosis is caused by infection with certain species of the genus Brucella and is characterized by bacterial persistence and inflammation of many host tissues. Handling all live Brucella involves risk of laboratory infection and very strict biosafety rules must be observed. In order to avoid these disadvantages, method based on the PCR-RFLP shows excellent typeability, reproducibility, stability, and epidemiological concordance. The omp2 locus contains two gene copies (named omp2a and omp2b) coding for porin proteins and has been found particularly useful for molecular typing and identification of Brucella at the species, biovar, or strain level. This study is designed to evaluate the molecular epidemiology of Brucella spp from human and livestock in Isfahan province, central region of Iran in order to use the findings in efficient disease prevention programs. MATERIALS AND METHODS: One hundred ninety blood samples were collected from human and cattle with active brucellosis and 40 aborted ewes fetuses were collected and genotyped using PCR-RFLP technique, DNA polymorphisms such as the restriction patterns of the PCR-amplified omp2a and omp2b genes. RESULTS: The molecular characterization performed to assess the species and the biovar of the Brucella strains. Analysis of the 230 isolates examined in this study generated three unique RFLP profiles. One of the profiles was the most common being present in 134/180. CONCLUSION: Our findings confirm abundance of B. melitensis, particularly biovar 1 in human and sheep are identical but B. abortus biovar 3 as the etiological agent of cattle brucellosis most frequently isolated in the Isfahan area. PMID- 26261805 TI - Effect of age on the phenotype of metabolic syndrome in developing country. AB - BACKGROUND: This study aimed to determine how age groups effect on the phenotype of metabolic syndrome (MetS) among Iranian population. MATERIALS AND METHODS: This cross-sectional study was conducted as part of Isfahan Healthy Heart Program. Height, weight, waist circumference, and blood pressure were measured by trained health-care professionals. MetS was defined as having three or more of the National Cholesterol Education Program III criteria. The relation between different age groups and different phenotypes of MetS was examined using the multinomial logistic regression. RESULTS: We found low high-density lipoprotein cholesterol (HDL-c) was the most common feature, followed by hypertriglyceridemia (HTG), abdominal obesity (ABO), hypertension (HTN), and high fasting blood glucose in decreasing order of prevalence. The most prevalent combination of MetS components was hypertrigeceridemia, low HDL-c and ABO (50.7%) in all subjects and especially in younger age group (63.2%). In elder age group, the most prevalent three components combination was HTG, Low HDL-c and HTN (43.9%). Logistic regression analysis demonstrated that elder subjects were at approximately 12 times higher risk of having the combination HTG, ABO, low HDL-c, and HTN (P < 0.001) compared to the middle age subjects who had a lower risk for the same combination; (2 [1.49-3.49]) (P < 0.001). CONCLUSION: This study provides a nationally representative estimate of the prevalence of different phenotypes of MetS across different age groups. Regarding different phenotypes of MetS in various age groups need to have important implications in the clinical management of these patients and the implementation of public health. PMID- 26261807 TI - Comparison of antibacterial activities of cadmium oxide nanoparticles against Pseudomonas Aeruginosa and Staphylococcus Aureus bacteria. AB - BACKGROUND: Inorganic antibacterial factors have bacterial resistance and high thermal stability. Inorganic nanomaterials which have new structures with biological, chemical and physical properties have been made since their applications due to their nano size. In this study, the antibacterial effect of cadmium oxide nanoparticles on Staphylococcus aureus and Pseudomonas aeruginosa bacteria was investigated. MATERIALS AND METHODS: The different concentrations (10 MUg/ml, 15 MUg/ml and 20 MUg/ml) of cadmium oxide nanoparticles were prepared and their effects were studied against considered bacteria in both solid and liquid media. RESULTS: The results showed that there is a direct relationship between inhibitory effect and amount of consumer dose of nanoparticles. Furthermore, it was observed that antibacterial properties of cadmium oxide nanoparticles on activity and growth of Staphylococcus aureus was more effective than Pseudomonas aeruginosa. CONCLUSION: This study showed that antibacterial effects of cadmium oxide nanoparticles on positive gram bacteria are stronger than negative gram bacteria and antibacterial effects of cdo nanoparticles against both bacteria, but Staphylococcus aureus bacteria were more sensitive to nanoparticles as compared to Pseudomonas aeruginosa. PMID- 26261808 TI - Effect of family members' voice on level of consciousness of comatose patients admitted to the intensive care unit: A single-blind randomized controlled trial. AB - BACKGROUND: Coma is one of the most important complications of brain injury. Comatose patients in the intensive care units are exposed to sensory deprivation. This study aims to survey the effect of family members' voice on level of consciousness of comatose patients hospitalized in the intensive care units. MATERIALS AND METHODS: In this single-blind randomized controlled trial, 40 comatose patients with brain injury with acute subdural hematoma in intensive care units were randomly assigned into two groups. The intervention group was stimulated twice a day each time 5-15 min with a recorded MP3 from family members' voice for 10 days. The patients' level of consciousness was measured with Glasgow Coma Scale before and after auditory stimulations. In the control group, GCS was measured without auditory stimulation with the same time duration like intervention group. Data analysis in software SPSS version 15 and using Chi square test, independent t-test, paired t- test and analysis of variance with repeated measures was done. RESULTS: On the first day before the intervention, there was no a statistically significant difference between the mean of GCS in both groups (P = 0.89), but on the tenth day after the intervention, there was a significant difference (P = 0.0001) between the mean GCS in both control and intervention groups. Also, there was a significant difference between the mean daily GCS scores in two groups (P = 0.003). The findings during ten days showed the changes in the level of consciousness in the intervention group from the 4(rd) day of the study were more in the mean daily GCS scores than control group. CONCLUSION: This study indicated that family members' voice can increase level of consciousness of comatose patients with acute subdural hematoma. PMID- 26261809 TI - Protective effects of Echium amoenum Fisch. and C.A. Mey. against cerebral ischemia in the rats. AB - BACKGROUND: This study was designed to evaluate the protective effect of Echium amoenum total anthocyanin extract (ETAE) on partial/transient cerebral ischemia in the rats. MATERIALS AND METHODS: Rats received ETAE (50, 100 and 200 mg/kg, i.p.) 30 min before the induction of cerebral ischemia. Cerebral ischemia was induced by bilateral common carotid arteries occlusion (BCCAO) for 30 min, followed by 72 h reperfusion. The neurological deficit, brain performance, and sensory motor function were assessed 48 h and 72 h after surgery. After sacrification, the brains were evaluated for myeloperoxidase (MPO) activity and histopathological changes. RESULTS: Our results showed that motor function significantly decreased in ischemia/reperfusion (I/R) group as compared to the sham group. Histopathological analysis exhibited the shrinkage and atrophy of the neurons in I/R group. ETAE at the dose of 200 mg/kg improved spontaneous activity and memory induced by cerebral ischemia compared to the control group and also decreased brain MPO activity following cerebral ischemia. However, it could not affect the ability to climbing, body proprioception, vibrissae touch and brain water content. In addition, pretreatment with ETAE at higher doses significantly reduced ischemia-induced neuronal loss of the brain. CONCLUSION: The anthocyanin rich fraction from E. amoenum was found to have protective effects against some brain damages postischemic reperfusion. However, further researches are required for investigating the exact mechanisms of the effect of this plant in the prevention of cerebral ischemia in human. PMID- 26261810 TI - The association between saliva control, silent saliva penetration, aspiration, and videofluoroscopic findings in Parkinson's disease patients. AB - BACKGROUND: Dysphagia is a common disorder among patients with Parkinson's disease (PD). It occurs in up to 80% of all (PD) patients during the early stages of the disease and up to 95% in the advanced stages; but professionals may not hear from the patients about dysphagia symptoms until these symptoms reach an advanced stage and lead to medical complications. MATERIALS AND METHODS: Thirty three PD patients (mean age 66.09 +/- 9.4 years; 24 men, nine women) participated in this study at our Neurology Institute, between April 20, 2013, and October 26, 2013. They were asked two questions; one about saliva control and the other about silent saliva penetration and aspiration. Next, they underwent the videofluoroscopic swallowing study (VFSS). RESULTS: The Pearson Correlation coefficient between the Penetration-Aspiration Scale (PAS) scores and question 1 scores was 0.48 (P < 0.05, =0.25), and there was a significant correlation between the PAS scores and question 2 scores, and also question 1 scores + question 2 scores (r = 0.589, P < 0.05, =0 and r = 0589, P < 0.05, =0). CONCLUSIONS: This study showed a significant correlation between the questions about saliva control, silent saliva penetration, and aspiration, and laryngeal penetration and aspiration during VFSS. Therefore, by using these two questions, the potential silent laryngeal penetration and aspiration during meals could be detected before it led to aspiration pneumonia. Taking the benefit of these questions, as a part of the swallowing assessment of PD patients, is recommended. PMID- 26261811 TI - The effects of unripe grape extract on systemic blood pressure and serum levels of superoxide dismutase, malondialdehyde and nitric oxide in rat. AB - BACKGROUNDS: The new lifestyle increases the incidence of hypertension. In Iranian folk medicine, it is believed that Verjuice obtained by unripe grape (Vitis vinifera) could control blood pressure. We tested the effects of unripe grape extract (UGE) in blood pressure alteration, serum antioxidant level and aorta endothelial permeability in rats. MATERIALS AND METHODS: Four groups of rats were treated daily by placebo and three different doses of UGE (50, 150 and 300 mg/kg/day). Four weeks later, the animals were anesthetized and catheterized. The direct mean arterial, systolic and diastolic pressures (MAP, SP and DP) were recorded. The endothelial permeability was determined and the serum levels of superoxide dismutase (SOD), malonaldialdehyde (MDA) and nitrite were measured. RESULTS: High dose of UGE increased MAP and SP significantly (P < 0.05) when compared with the control group. Decrease of MDA and increase of SOD and nitrite also were detected statistically in animals treated with high dose of UGE (P < 0.05). No difference in aorta endothelial permeability was observed between the groups. CONCLUSION: The effect of UGE on blood pressure was dose dependent. High dose of UGE increased MAP and SP although its antioxidant activity was significantly high. Such observation mechanisms need to be defined. PMID- 26261812 TI - Molecular identification of Acinetobacter baumannii isolated from intensive care units and their antimicrobial resistance patterns. AB - BACKGROUND: Acinetobacter baumannii is one of the most important pathogens in hospital-acquired infections especially in intensive care units (ICUs). This opportunistic pathogen can be easily isolated from water, soil, and hospital facilities. A. baumannii as a nosocomial opportunistic pathogen is resistant to a wide range of antibiotics and responsible for multiple infections, including bacteremia, pneumonia, meningitis, urinary tract infections, and surgical wounds. The aim of this study was to determine frequency and resistance patterns of A. baumannii isolated in ICUs of Isfahan Hospitals. MATERIALS AND METHODS: During 1 year period (2012-2013), 350 specimens were collected from ICUs of Isfahan hospitals. The isolates were characterized as A. baumannii by conventional phenotypic, biochemical tests and confirmed by PCR for OXA-51-like gene. Susceptibility of isolates was determined by standard disk diffusion method according to CLSI. RESULTS: From total of 350 specimens, 43 isolates were A. baumannii. The antimicrobial patterns of isolates showed that 53.5% of isolates were resistant to amikacin, 83.7% to tetracyclin, 86% to ceftazidime, 90.7% to Trimethoprim sulfametoxazol, 93% to imipenem, cefepime, meropenem, ampicillin sulbactam. All isolates were resistant to ciprofloxacin. CONCLUSION: This study showed a high resistance of A. baumannii to a wide range of antimicrobial agent. It is necessary to adopt appropriate strategies to control the spread of the bacteria in care unit centers and wards. PMID- 26261813 TI - Causes and rates of revision total knee arthroplasty: Local results from Isfahan, Iran. AB - BACKGROUND: Knee replacement is one of the most frequently performed surgical procedures in the world. Local data on revision total knee arthroplasty (TKA) are limited. This study aims to assess the rates and causes of revision TKA in Kashani Hospital (Isfahan, Iran) from 2011 to 2013. MATERIALS AND METHODS: We assessed all primary TKA and revision TKA procedures performed from 2011 to 2013 for the rate and causes of failures. Demographic data, duration from primary TKA to revision TKA and underlying diagnosis for primary TKA were also assessed. RESULTS: Overall, 353 primary TKA procedures carried out in this period. The overall revisions following primary TKA in this period was 24 cases, indicating a revision burden of 6.8%. The most common cause of revision TKA was infection, which was in 16 cases (44.4%). Other causes included patellar complications, mechanical loosening of both tibia and femur, mechanical loosening of tibia, instability, and periprosthetic fracture. The main revision procedures were all component revision, tibial component revision, isolated tibial insert exchange and patellar tendon repair. The most common revision procedure was two stage all component revision, which was carried out in 13 subjects (36.1%). CONCLUSION: Local indications for revision TKA are mainly similar to those in other large centers. As compared with other centers, with considering the follow-up time, revision burden is relatively higher in this center. PMID- 26261814 TI - The effect of problem solving and decision making skills on tendency to depression and anxiety in patients with type 2 diabetes. AB - BACKGROUND: Diabetes is the most prevalent disease that has involved 177 million people all over the world and, due to this, these patients suffer from depression and anxiety and they should use special methods for controlling the same. The aim of this research is the study of the effect of problem solving and decision making skill on the rate of the tendency to depression and anxiety. MATERIALS AND METHODS: This research is a quasi-experimental (case-control) study. Statistically, the population of the present study was all diabetic patients of Qaemshahr who were controlled by physicians in 2011-2012. Thirty files were selected randomly from them and divided into two 15 patients' groups (control and subject group) randomly. The measurement tools were Back depression inventory (21 items) and Zank anxiety questionnaire that were distributed among two groups. Then, the subject group participated in eight sessions of teaching problem solving and decision making courses separately, and the second group (control group) did not receive any instruction. RESULTS: Finally, both groups had passed post-test and the data obtained from the questionnaires were studied by variance analysis statistical methods. CONCLUSION: The results showed that teaching problem solving and decision making skills was very effective in reducing diabetic patients' depression and anxiety and resulted in reducing their depression and anxiety. PMID- 26261815 TI - Topical pyruvic acid (70%) versus topical salicylic acid (16.7%) compound in treatment of plantar warts: A randomized controlled trial. AB - BACKGROUND: Recurrence rate is considerable with current topical treatments of plantar warts. We compared the efficacy of topical pyruvic acid (70%) with salicylic acid (16.7%) compound in treating multiple plantar warts. MATERIALS AND METHODS: In this randomized controlled trial, 60 patients with multiple plantar warts were equally randomized to receive either pyruvic acid 70% or compound salicylic acid solution (salicylic acid 16.7%, lactic acid 16.7%, and collodion 100%) that was topically applied twice a day for 4 weeks. Patients were visited every 2 weeks for 1 month after starting treatment and then every 1 month for another 2 months. The number and size of warts, treatment complications (pain, burning, scar, pigmentation, and crust), and recurrence were evaluated. RESULTS: Warts' number was decreased by -13.12 +/- 25.6% with pyruvic acid and by -23.0 +/ 28.0% with compound salicylic acid (P = 0.159) after treatment. Warts' size was decreased by -43.47 +/- 57.0% with pyruvic acid and by -37.40 +/- 32.76% with compound salicylic acid (P = 0.615) after treatment. There was no difference between the two groups in cumulative incidence of treatment complications (P > 0.05). Also, there was no difference between the two groups in recurrence rate at 2 months (10 vs. 16.7%, P = 0.500) or at 3 months after treatment (3.3 vs. 6.7%, P = 0.335). CONCLUSION: Topical pyruvic acid and compound salicylic acid had the same efficacy and complications in treating plantar warts. Decision for choosing the treatment can be made based on the costs and individual factors as well as patients preferences. PMID- 26261816 TI - Investigation of purification process stresses on erythropoietin peptide mapping profile. AB - BACKGROUND: Full compliance of recombinant protein peptide mapping chromatogram with the standard reference material, is one of the most basic quality control tests of biopharmaceuticals. Changing a single amino acid substitution or side chain diversity for a given peptide changes protein hydrophobicity and causes peak shape or retention time alteration in a peptide mapping assay. In this work, the effect of different stresses during the recombinant erythropoietin (EPO) purification process, including pH 4, pH 5, and room temperature were checked on product peptide mapping results. MATERIALS AND METHODS: Cell culture harvest was purified under stress by different chromatographic techniques consisting of gel filtration, anionic ion exchange, concentration by ultrafiltration, and high resolution size exclusion chromatography. To induce more pH stresses, the purified EPO was exposed to pH stress 4 and 5 by exchanging buffer by a 10 KDa dialysis sac overnight. The effects of temperature and partial deglycosylation (acid hydrolysis) on purified EPO were also studied by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and peptide mapping analysis. Removal of sialic acid by mild hydrolysis was performed by exposure to two molar acetic acid at 80 degrees C for 3 h. RESULTS: No significant effect was observed between intact and stressed erythropoietin peptide mapping profiles and SDS-PAGE results. To validate the sensibility of the technique, erythropoietin was partially acid hydrolyzed and significant changes in the chromatographic peptide map of the intact form and a reduction on its molecular weight were detected, which indicates some partial deglycosylation. CONCLUSIONS: Purification process does not alter the peptide mapping profile and purification process stresses are not the cause of peptide mapping noncompliance. PMID- 26261817 TI - Reference range of the weekly uterine cervical length at 8 to 38 weeks of gestation in the center of Iran. AB - BACKGROUND: There is an inverse relation between the uterine cervical length during pregnancy and the frequency of preterm delivery. The purpose of this study was to construct a chart and evaluate the cervical length at 8 to 38 weeks of normal gestation in the center of Iran. MATERIALS AND METHODS: Uterine cervical length was measured on 930 asymptomatic pregnant women by abdominal ultrasonographic technique. For statistical evaluation, regression analysis and calculation of percentiles were performed. RESULTS: Our data show a significant decrease in uterine cervical length with increasing gestational age. The mean uterine cervical length exhibits minimal changes from 10 to 24 weeks for most women in this study, although the shortening is more prominent at 33 to 38 weeks' gestation. The mean shortening of the uterine cervical length between the second and the ninth months was 14.82% (P < 0.05). Also, the cervical length means in trimesters 1, 2 and 3 were 39.30 +/- 4.33, 38.28 +/- 5.13 and 36.58 +/- 4.58 mm, respectively. The third trimester showed a significant reduction (P < 0.05) in cervical length compared to the first and second trimesters (6.92% and 4.44%, respectively). New charts with the 5(th), 10(th), 50(th), 90(th), and 95(th) percentile are presented. CONCLUSION: Our study provides a new chart and reference values for normal uterine cervical length throughout gestation based on a large sample in the center of Iran. There was a progressive decrease in mean uterine cervical length with increasing gestational age in the population of this study. Our established charts for uterine cervical length throughout gestation might be more useful than a single cut-off value for more efficient prevention and management of preterm birth. PMID- 26261818 TI - Study of C-MYC amplification and expression in Iranian gastric cancer samples using CISH and IHC methods. AB - BACKGROUND: Gastric cancer is the fourth most frequent malignancy and the second cause of cancer-related mortality worldwide. It has been suggested that in gastric carcinogenesis, the C-MYC gene has an important function. The objective of this study is to establish the preference of Chromogenic in situ hybridization (CISH) and Immunohistochemistry (IHC) in the diagnosis and prognosis of gastric cancer. MATERIALS AND METHODS: Samples comprised of 50 randomly selected patients of whom 40 were male and 10 female. To evaluate the MYC copy number and its protein expression, CISH and IHC analyses were performed for 50 gastric adenocarcinomas, in Iran. RESULTS: The location of the tumor in 64% of the patients was the fundus, and in 72% of patients, the tumors were of a diffuse type; 22 samples showed no amplification, and 28 samples were with amplification. MYC immunoreactivity was observed in 13 samples. Twelve samples showed both MYC amplification and MYC immunoreactivity. In addition, among the 28 CISH+ samples, 12 samples had positive signals for IHC and 16 samples had negative signals for IHC. A majority of the IHC-negative patients had no amplification, but only one patient with IHC positive had no amplification. CONCLUSION: Our conclusion was that for the management and treatment of gastric cancer, and for special attention of clinicians, for prognosis and tumor progression, the CISH was a better and more feasible test than IHC, in regard to the sensitivity and specificity. PMID- 26261820 TI - Dietary intake of Zinc, serum levels of Zinc and risk of gastric cancer: A review of studies. AB - Gastric cancer (GC) is considered as most fourth common cancer in the world. Findings from animal, experimental and epidemiologic studies indicate that diet plays an important role in the etiology of stomach cancer. Among dietary factors, Zinc status has received great attention in recent years. The purpose of the present study was to review the association of serum levels of Zinc, dietary intake of Zinc and GC risk. A complete search was performed about the association of Zinc status and risk of GC was in databases electronic through such as ISI web of science, PubMed, Scopus, IrMedx and SID. Our results of current review suggest that dietary intake of Zinc and serum levels of Zinc are lower in GC patient. In other word, high serum levels of Zinc may be protective in GC risk. However, it seems further studies in particular epidemiological studies with large scale setting are required to reach a definite conclusion. PMID- 26261819 TI - Current status and patent prospective of animal models in diabetic research. AB - Diabetes mellitus is a heterogeneous complex metabolic disorder with multiple etiology which characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action or both. The widespread occurrence of diabetes throughout the world has increased dramatically over the past few years. For better understanding, appropriate animal models that closely mimic the changes in humans needed, as vital tool for understanding the etiology and pathogenesis of the disease at the cellular/molecular level and for preclinical testing of drugs. This review aims to describe the animal models of type-1 diabetes (T1Ds) and T2Ds to mimic the causes and progression of the disease in humans. And also we highlight patent applications published in the last few years related to animal models in diabetes as an important milestone for future therapies that are aim to treating diabetes with specific symptoms and complications. PMID- 26261821 TI - Annexin V FITC conjugated as a radiation toxicity indicator in lymphocytes following radiation overexposure in radiotherapy programs. AB - BACKGROUND: Following human radiation exposure in hospital or accidents, dose assessments are of prime importance in radiation accidents. These issues are of continuing importance with respect to socioeconomic policy relating to the industrial and medical uses of ionizing radiation, and also for risk assessment among people who are occupationally exposed to low and/or high linear energy transfer (LET) radiation, such as astronauts, pilots, stewardesses, nuclear power plant workers, and victims of radiation accidents. MATERIALS AND METHODS: In this study, an assay for assessing radiation dose based on the induction of apoptosis in human T-lymphocytes was done to examine T-lymphocyte cells isolated from the fresh blood of 16volunteers, cultured and exposed to gamma rays. Radiation induced apoptosis (RIA) was assessed by flow cytometric identification of cells displaying apoptosis-associated DNA condensation. RESULTS: Dose-response experiments showed that at 2Gy dose level of radiotherapy programs, the RIA frequency was significantly above control. Apoptotic levels significantly depend on the dose of radiation rather than the donor. CONCLUSION: The results demonstrate the potential use of this assay as a biological indicator of radiation toxicity, optimizing patient dose in radiotherapy and biological dosimetry process. PMID- 26261823 TI - Expression of prostaglandin I2 (prostacyclin) receptor in blood of migraine patients: A potential biomarker. AB - BACKGROUND: Migraine is the most common chronic neurological disorders that may be associated with vasodilatation. According to the role of prostaglandin I2 (prostacyclin) receptor (PTGIR) in migraine as a receptor, which acts in vasodilatation, we decided to study the changes of PTGIR expression in migraine patients in relation to a suitable control group. MATERIALS AND METHODS: Extracted mRNA from lymphocytes of 50 cases and 50 controls was used to synthesize cDNA. Real-time polymerase chain reaction was performed, and the data were analyzed. Our results show that PTGIR mRNA expression in cases was significantly higher than the control group (P = 0.010). RESULTS: In conclusion, mRNA expression of PTGIR in the blood of people with migraines could be considered as a biomarker. CONCLUSION: In addition, repression of PTGIR gene expression by methods such as using siRNA is probably suitable for therapy of migraine patients. PMID- 26261822 TI - Conventional, molecular methods and biomarkers molecules in detection of septicemia. AB - Sepsis is a leading cause of morbidity and mortality in hospitalized patients worldwide and based on studies, 30-40% of all cases of severe sepsis and septic shock results from the blood stream infections (BSIs). Identifying of the disease, performing laboratory tests, and consequently treatment are factors that required for optimum management of BSIs. In addition, applying precise and immediate identification of the etiologic agent is a prerequisite for specific antibiotic therapy of pathogen and thereby decreasing mortality rates. The diagnosis of sepsis is difficult because clinical signs of sepsis often overlap with other noninfectious cases of systemic inflammation. BSIs are usually diagnosed by performing a series of techniques such as blood cultures, polymerase chain reaction-based methods, and biomarkers of sepsis. Extremely time-consuming even to take up to several days is a major limitation of conventional methods. In addition, yielding false-negative results due to fastidious and slow-growing microorganisms and also in case of antibiotic pretreated samples are other limitations. In comparison, molecular methods are capable of examining a blood sample obtained from suspicious patient with BSI and gave the all required information to prescribing antimicrobial therapy for detected bacterial or fungal infections immediately. Because of an emergency of sepsis, new methods are being developed. In this review, we discussed about the most important sepsis diagnostic methods and numbered the advantage and disadvantage of the methods in detail. PMID- 26261824 TI - Comparison of five methods in predicting difficult laryngoscopy: Neck circumference, neck circumference to thyromental distance ratio, the ratio of height to thyromental distance, upper lip bite test and Mallampati test. AB - BACKGROUND: Preoperative airway assessment tests have been presented to help in anticipating a difficult airway. We conducted this study to compare five methods in prediction of difficult laryngoscopy: Neck circumference (NC), NC to thyromental distance ratio (NC/TMD), the ratio of height to thyromental distance (RHTMD), upper lip bite test (ULBT) and Mallampati test (MMT). These five methods are the most commonly used ones and have different powers for it. It was not clear which of these methods predicts difficult laryngoscopy better. MATERIALS AND METHODS: Six hundred consecutive patients participated in this study. NC, NC/TMD and RHTMD were measured, and ULBT and MMT were performed and recorded. The laryngoscopy view was graded according to Cormack and Lehane's scale (CLS) and difficult laryngoscopy was defined as CLS grades 3 and 4. Accuracy of tests in predicting difficult laryngoscopy was assessed using the area under a receiver operating characteristic curve. RESULTS: The area under the curve in ULBT and RHTMD were significantly larger than that in TMD, NC and MMT. No statistically significant differences were noted between TMD, NC and MMT (all P > 0.05) (ULBT = RHTMD > NC/TMD > TMD = NC = MMT). RHTMD (>22.7 cm) exhibited the highest sensitivity (sensitivity = 64.77, 95% confidence interval [CI]: 53.9-74.7) and the most specific test was ULBT (specificity = 99.41%, 95% CI: 98.3-99.9). CONCLUSION: RHTMD and ULBT as simple preoperative bedside tests have a higher level of accuracy compared to NC/TMD, TMD, NC, MMT in predicting a difficult airway. PMID- 26261825 TI - Comparison of two walk tests in determining the claudication distance in patients suffering from peripheral arterial occlusive disease. AB - BACKGROUND: The purpose of this study was to compare the six-minute walk test (6MWT) and the incremental shuttle walk test (ISWT) in terms of the initial onset of pain (IOP), maximal claudicating pain (MCP), maximum walking distance (MWD), initial ankle brachial index (IABI), post ankle brachial index (PABI), and difference in ankle brachial index (DFABI), as well as to correlate changes in IOP and MWD, MCP and MWD, IABI and MWD, PABI and MWD, and DFABI and MWD in the 6MWT and ISWT. MATERIALS AND METHODS: Participants (n = 19, 17 men and 2 women) were randomly allocated to the 6MWT or ISWT and crossed over to the other test after 24 hours. The baseline ankle brachial index (ABI) measurements were taken using the Doppler, following which the participants performed the tests. Post test MWD, IOP, MCP, and ABI were measured. The paired t test was used pre- and post the walk test and the Pearson correlation was used to find any relationship between the desired variables. RESULTS: The paired t test at 95% confidence interval for IABI and PABI (P > 0.05) was insignificant for the 6MWT and ISWT. The Pearson correlation of MWD with IOP showed a fair correlation, and the correlation of MWD to MCP showed a strong correlation in ISWT. CONCLUSION: ISWT can be of vital importance as a tool to assess the functional status of patients suffering from Peripheral Arterial Occlusive Disease (PAOD) in both the clinical and research areas, and reflects a better assessment of the functional limitation when walking with PAOD as compared to the 6MWT. PMID- 26261826 TI - Prophylactic effect of topical silica nanoparticles as a novel antineovascularization agent for inhibiting corneal neovascularization following chemical burn. AB - BACKGROUND: Angiogenesis-related corneal blindness includes the spectrum of corneal diseases that are caused by pathological angiogenesis, leading to untoward visual impairment. The purpose of this study was to investigate the antineovascularization effect of topical silica nanoparticles (SiNPs) in inhibiting chemical-burn-induced corneal neovascularization. MATERIALS AND METHODS: A total number of 20 corneas of 10 Wistar Albino rats were included in this study. Silver nitrate cauterization was pressed to the central cornea for 5 s to induce corneal neovascularization. They were randomly allocated to case and control groups (ten eyes in each group). SiNPs were synthesized by the reverse microemulsion method. SiNPs drop 1 mg/ml was started in ten eyes and artificial tear drop was started in the control group (ten eyes) immediately after chemical cauterization. Video-based photography was performed before and after treatment. Corneal image analysis was performed on each cornea using an image analysis software program. All rats were euthanized and the eyes were sent for histopathologic examinations14 days after chemical cauterization. RESULTS: Scanning electron microscopy (SEM) images showed spherical-shaped particles. The mean size and polydispersity index of prepared SiNPs were 30.1 +/- 5.6 nm and 0.254 +/- 0.11, respectively. Fourteen days after chemical cauterization, the mean vascularized corneal area was 21% of total corneal area in the case group and 85% in the control group (P < 0.05). The control group revealed more extensive intrastromal vascularization compared with the case group in histopathologic examinations (P < 0.05). CONCLUSIONS: SiNPs is an effective modality for inhibiting corneal neovascularization following chemical burn in an experimental model. Further investigations are suggested for evaluation of its safety and efficacy in human eyes. PMID- 26261827 TI - The effect of cyclic nucleotide analog drugs on the mediators release from basophils. AB - BACKGROUND: The cyclic nucleotides, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), are intracellular second messengers that play an important role in modulating inflammatory cells involved in allergic diseases. In general, cAMP suppresses the activity of immune and inflammatory cells. We aim to evaluate the roles of cAMP and cGMP in regulating basophil activity. MATERIALS AND METHODS: Basophil-enriched preparations were incubated with analogs and then challenged with anti-IgE or IL-3 (4 or 24 hours). Supernatants were assayed for histamine, IL-4, and IL-13 release. The effects of Sp-8-CPT-cAMPS and Sp-8-CPT-cGMPS on IL-3-dependent mediator release from basophils were determined. The cells were pre-incubated with an analog and then incubated with IL-3 for 24 hours. RESULTS: Sp-8-CPT-cAMPS was an effective (P < 0.05) inhibitor of IL-4, IL-13, and histamine release from basophils. However, paradoxically, Sp-8-CPT-cGMPS enhanced histamine release and IL-13 generation, but by contrast, had little effect on IL-4 generation. Sp-8-CPT-cGMPS inhibited cytokine generation, but enhanced the release of histamine release to a modest extent. CONCLUSION: This study shows that the cAMP/protein kinase A (PKA) pathway may be inhibitory to the IgE- and non-IgE-dependent release of mediators from basophils. PMID- 26261828 TI - How health information is received by diabetic patients? AB - BACKGROUND: Knowledge of correct information-seeking behavior by the patients can provide health specialists and health information specialists with valuable information in improving health care. This study aimed to investigate the passive receipt and active seeking of health information by diabetic patients. MATERIALS AND METHODS: A survey method was used in this research on 6426 diabetic patients of whom 362 patients were selected by a no percentage stratified random sampling. The Longo information-seeking behavior questionnaire was used to collect data and they were analyzed by SPSS 20 software. RESULTS: The most common information source by diabetic patients was practitioners (3.12). The minimum usage among the information sources were from charity organizations and emergency phone lines with a usage of close to zero. The amount of health information gained passively from each source has the lowest average of 4.18 and usage of this information in making health decision has the highest average score of 5.83. Analysis of the data related to active seeking of information showed that knowledge of available medical information from each source has the lowest average score of 3.95 and ability in using the acquired information for making medical decisions has the highest average score of 5.28. The paired t-test showed that differences between passive information receipt (41.68) and active information seeking (39.20) considered as statistically significant (P < 0.001). CONCLUSION: Because diabetic patients are more passive information receivers than active information seekers, the health information must be distributed by passive means to these patients. In addition, information-seeking behavior during different time periods should be investigated; to identify more effective distribution of health information. PMID- 26261829 TI - The effectiveness of lavender essence on strernotomy related pain intensity after coronary artery bypass grafting. AB - BACKGROUND: Considering the side effects of pharmacological methods, there has been a suggestion to use nonpharmacological methods such Aromatherapy following coronary artery bypass grafting (CABG). This study aims to evaluate the effectiveness of lavender 2% aromatherapy on sternotomy pain intensity after coronary artery bypass graft surgery in patients who have undergone surgery. MATERIALS AND METHODS: During this clinical trial, 50 patients who were candidates for CABG, were randomly divided into two equal groups, that is, the control group (n = 25) and the case group (n = 25). Following CABG, the case group received two drops of 2% lavender oil every 15 minutes with supplemental oxygen and the control group received only supplemental oxygen through a face mask. The data collection tools comprised of the demographic check list and visual analog scale (VAS) for evaluating the pain intensity. The pain intensity were assessed pre- and five, 30, and 60 minutes post aromatherapy. The final data were analyzed by the t-test and chi-squared test. RESULTS: The findings showed that the pain perception intensity in the case group was lower than that in the control group at the 30- and 60-minute phases after intervention (P < 0.0001). CONCLUSION: The result indicated that aromatherapy can be used as a complementary method in postoperative pain reduction, as it reduced pain. The patients require two sedative drugs, and moreover, it avoids expenses of treatment. PMID- 26261830 TI - Antigenic profile of heat-killed versus thimerosal-treated Leishmania major using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. AB - BACKGROUND: Leishmania is a parasitic protozoan of trypanosomatidae family which causes a wide spectrum of diseases ranging from self-healing cutaneous lesions to deadly visceral forms. In endemic areas, field trials of different preparations of Leishmania total antigen were tested as leishmaniasis vaccine. Two preparations of killed Leishmania major were produced In Iran, which were heat killed vaccine called autoclaved L. major (ALM) and thimerosal-treated freeze thawed vaccine called killed L. major (KLM). In this study, the protein content of both ALM and KLM were compared with that of freshly harvested intact L. major promastigotes using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). MATERIALS AND METHODS: L. major (MRHO/IR/75/ER) from pre-infected Balb/c mice was isolated with modified Novy-MacNeal-Nicolle (NNN) medium and then subcultured in liquid RPMI 1640 medium supplemented with fetal calf serum (FCS) 20% for mass production. Two preparations of KLM and ALM were produced by Razi Vaccine and Serum Research Institute, Iran, under WHO/TDR supervision. Electrophoresis was performed by SDS-PAGE method and the gel was stained by Coomassie brilliant blue dye. The resultant unit bands were compared using standard molecular proteins. RESULTS: Electrophoresis of the two preparations produced many bands from 10 kDa to 100 kDa. KLM bands were much like those of freshly harvested intact L. major. CONCLUSION: It is concluded that although there are similar bands in the three forms of Leishmania antigens, there are some variations which might be considered for identification and purification of protective immunogens in a total crude antigen, and detection of their stability is essential for the production and marketing of a putative vaccine. PMID- 26261831 TI - The role of imaging in acute appendicitis and the need for histopathologic validation. PMID- 26261832 TI - General versus spinal anesthesia in joint arthroplasties. PMID- 26261833 TI - Spinal anesthesia: the new gold standard for total joint arthroplasty? PMID- 26261834 TI - Unlocking the bone: Fcgamma-receptors and antibody glycosylation are keys to connecting bone homeostasis to humoral immunity. AB - Bone tissue is characterized by a constant remodeling process mediated by bone resorbing osteoclasts and bone forming osteoblasts. During autoantibody mediated autoimmune diseases, such as inflammatory arthritis, this balance is disturbed and the de novo generation of osteoclasts through cross-linking of activating Fcgamma-receptors (FcgammaRs) expressed on osteoclasts results in excessive bone erosions and joint destruction. A recent study by Negishi-Koga and colleagues now provides conclusive evidence, that FcgammaRs may also play a crucial role for bone homeostasis during the steady state, further highlighting the tight interactions between the bone and immune system. PMID- 26261835 TI - Fresh osteochondral allografts in the knee: only a salvage procedure? AB - The role of fresh allogeneic osteochondral allograft transplantation (OCA) in the cartilage repair algorithm has been long debated and this procedure is primarily considered as a salvage procedure, to be used when other, simple, techniques have failed. Gracitelli et al. in a retrospective comparison of patients who received OCA as primary treatment or as a salvage procedure, demonstrates that the outcome of this procedure is minimally influenced by a previous failed treatment and that OCA represents an effective solution for both primary and revision surgery of chondral and osteochondral lesions of the knee. In particular, optimal indications for OCA seem to be revision of previously failed bone marrow stimulation techniques with an impaired subchondral bone plate and primary treatment of large osteochondral defects. PMID- 26261836 TI - A paradigm shift in vaccine production for pandemic influenza. PMID- 26261837 TI - Robotic-assisted right middle lobectomy. PMID- 26261838 TI - Robotic-assisted segmentectomy of lingual segment of the left upper pulmonary lobe. PMID- 26261839 TI - Robotic-assisted right middle lobectomy for poorly differentiated squamous cell carcinoma. PMID- 26261840 TI - Robotic-assisted left inferior lobectomy. PMID- 26261841 TI - Robotic-assisted right upper lobectomy. PMID- 26261842 TI - Pulmonary arteriovenous malformation-etiology, clinical four case presentations and review of the literature. AB - Pulmonary arteriovenous malformation (PAVM) is a rare clinical condition with abnormal direct communication between the branches of pulmonary artery and vein. It may occur as an isolated anomaly or in association with hereditary hemorrhagic telangiectasia (HHT). Although these vascular pulmonary pathologies are quite uncommon, they are the important part of the differential diagnosis of common pulmonary problems such as hypoxemia and pulmonary nodules. The diagnosis of PAVM in patients remains a diagnostic challenge to the emergency physician. The most common clinical signs of PAVM are recurrent episodes of epistaxis and hemoptysis, so surgical resection is deemed the best curative option to avoid further episodes and recurrence of hemoptysis. Quite often the diagnosis is established after pathohistological examinations. We report a case of a female patient with a massive recurrent hemoptysis and without pathologic radiological findings which would suggest to PAVM and who was successfully treated with lobectomy. PMID- 26261843 TI - Brexpiprazole: a new dopamine D2receptor partial agonist for the treatment of schizophrenia and major depressive disorder. AB - Brexpiprazole is a dopamine D2receptor partial agonist. Compared with aripiprazole, it is more potent at 5-HT1A receptors and displays less intrinsic activity at D2receptors. Brexpiprazole also has potent antagonistic activity at 5 HT2A as well as alpha-adrenergic receptors. In addition to results from phase II trials, data are available from two pivotal phase III, randomized, placebo controlled trials of brexpiprazole for the acute treatment of schizophrenia and two pivotal phase III, randomized, placebo-controlled trials of adjunctive brexpiprazole for the acute treatment of major depressive disorder in patients with inadequate response to antidepressant medication treatment. Overall tolerability is promising, with rates of discontinuation due to adverse events lower or slightly higher than that observed for placebo. Although overall akathisia was more commonly observed with brexpiprazole than with placebo, the absolute risk increase attributable to brexpiprazole appears small. Short-term weight gain appears modest; however, outliers with an increase of >= 7% of body weight were evident in open-label long-term safety studies. PMID- 26261844 TI - Hydrocodone bitartrate for chronic pain. AB - Hydrocodone bitartrate is the most commonly used drug for acute and chronic pain in the U.S. with over 135 million prescriptions in 2012. The U.S. is the primary consumer of hydrocodone, using 99% of the global supply for 4.4% of the global population. With its easy availability and abuse patterns, hydrocodone has been touted as a primary driver of opioid-related abuse and misuse. There are no clinical efficacy studies of hydrocodone in short-acting form in combination with acetaminophen or ibuprofen in chronic pain. Hydrocodone has been approved with two long-term formulations since 2014. The FDA has rescheduled hydrocodone from Schedule III to Schedule II which went into effect on October 6, 2014, along with a limit on added acetaminophen of 325 mg for each dose of hydrocodone. This review examines the evolution of hydrocodone into a common and yet controversial drug in the U.S. with its pharmacokinetics, pharmacodynamics, safety and efficacy. PMID- 26261845 TI - Generic Pharmaceutical Association (GPhA) - 2015 CMC Workshop (June 9-10, 2015 - Bethesda, Maryland, USA). AB - Nearly 400 professionals attended the 2-day Generic Pharmaceutical Association (GPhA) workshop dedicated to fostering discussions on the FDA's chemistry, manufacturing and controls (CMC) expectations for abbreviated new drug applications (ANDAs), enhanced regulatory filing requirements, and other topics, as CMC takes root in the Office of Pharmaceutical Quality (OPQ). Following the keynote address by Janet Woodcock, Director of the FDA's Center for Drug Evaluation and Research (CDER) and Acting Director of OPQ, and an update from the Office of Generic Drugs (OGD) by Ted Sherwood, Acting Director of the OGD's Office of Regulatory Operations, plenary sessions took place covering OPQ updates, management plans, Generic Drug User Fee Amendments of 2012 (GDUFA) backlog, year 1 and 2 cohorts, drug substance, defining starting materials, quality related refuse-to-receive standards, risk and team-based integrated quality assessment, deficiencies and information requests - CMC submissions, emerging technologies, compliance and inspection, lifecycle management of drug products, quality metrics, pharmaceutically relevant dissolution specifications, and communication and project management. This report will provide a summary of conference highlights. PMID- 26261846 TI - European Hematology Association - 20th Annual Congress (June 11-14, 2015 - Vienna, Austria). AB - The Annual Congress of the European Hematology Association, now in its 20th year, brought together specialists in all areas of hematology research to present new data on ongoing research and share innovative ideas to aid in the treatment and diagnosis of many hematological diseases. Clinical and translational research was presented along with technological advancement in diagnostics and risk-assessment strategies. The congress afforded attendees time for networking with representatives from many disciplines associated with hematological research, including academia, industry and patient advocacy groups. This report will cover the most interesting presentations relating to therapeutics for a range of hematological conditions. PMID- 26261847 TI - Alzheimer's Association International Conference on Alzheimer's Disease 2015 (AAIC 2015) (July 18-23, 2015 - Washington, D.C., USA). AB - The Alzheimer's Association International Conference (AAIC) was held in Washington, D.C. this year. It is the world's largest meeting of the dementia research community, connecting care providers, clinicians and investigators. The extent of efforts being made in the field of Alzheimer's research was demonstrated by the wide and varied program at the conference. This report focuses on some of the therapeutic highlights from the first two poster sessions. PMID- 26261848 TI - Nintedanib in idiopathic pulmonary fibrosis. AB - Idiopathic pulmonary fibrosis (IPF) conveys a median survival of 3 years and until recently has lacked effective therapies. Nintedanib, an orally available, small-molecule tyrosine kinase inhibitor with selectivity for vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) receptors has recently been shown, in two pivotal phase III studies, to effectively slow IPF disease progression. Consequently, nintedanib was given accelerated approval by the FDA in October 2014 for the treatment of IPF. This monograph explores the preclinical rationale for the antifibrotic role of nintedanib and provides an overview of the available data on pharmacokinetics, efficacy and safety. PMID- 26261849 TI - Nintedanib, a novel triple angiokinase inhibitor for the treatment of non-small cell lung cancer. AB - Lung cancer is the leading cause of cancer-related deaths worldwide. Recent advances involving targeted therapies are promising, but most patients do not have an "oncogene addicted" disease. A platinum doublet chemotherapy regimen has been the mainstay of therapy since 1997. The addition of antiangiogenic agents to traditional chemotherapy has improved survival in patients with non-small cell lung cancer. However, these agents are limited by serious adverse events such as thromboembolism, bowel perforation and hemorrhage and by the development of resistance. Nintedanib is a novel, orally available triple angiokinase inhibitor that targets three important pathways involved in the initiation and propagation of angiogenesis in tumors, the VEGF, FGF and PDGFR pathways. Phase I and II trials have identified the maximum tolerated dose in monotherapy and in combination with traditional chemotherapy. The toxicity profile is tolerable and reversible, dominated by transaminitis and gastrointestinal side effects. The phase III LUME-lung 1 study (NCT00805194) compared docetaxel, a standard treatment in the second line, with docetaxel in combination with nintedanib. Progression-free survival was 3.4 months in the combination group compared to 2.7 months in the docetaxel group, (HR 0.79, 95% CI 0.68-0.92, P = 0.0019). There was a significant improvement in overall survival in adenocarcinoma patients, 12.6 vs. 10.3 months (HR 0.83, 95% CI 0.7-0.99, P = 0.036). Based on the results of this study, nintedanib has been approved by the EMA in Europe, as a second-line treatment in patients with adenocarcinoma. It is a promising, well-tolerated therapy that is currently being investigated in multiple different tumor types. PMID- 26261850 TI - Omalizumab is efficacious for management of recalcitrant, antihistamine-resistant chronic urticaria. AB - Chronic urticaria continues to be a challenging condition for both patients and physicians. Despite improved understanding of chronic urticaria, many patients continue to experience ongoing symptoms and impaired quality of life. Omalizumab is a recombinant humanized monoclonal antibody that binds to the domain at which IgE binds to the high-affinity IgE receptor on mast cells and basophils. The efficacy of omalizumab for antihistamine-resistant chronic urticaria has been demonstrated in several randomized controlled trials as well as observational studies. Omalizumab is generally well tolerated, and is associated with less potential for harm compared with other therapeutic alternatives (e.g., calcineurin inhibitors) for recalcitrant chronic urticaria. Omalizumab has become the best-studied agent for treatment of antihistamine-resistant chronic urticaria, and the agent for which the data in support of its efficacy is most methodologically sound. Omalizumab is an effective therapeutic option for patients with recalcitrant chronic urticaria. PMID- 26261851 TI - American Psychiatric Association - 168th Annual Meeting (May 16-20, 2015 - Toronto, Canada). AB - The theme of this year's American Psychiatric Association (APA) meeting was 'Psychiatry: integrating body and mind, heart and soul', with special focus given to advances in basic and cognitive neuroscience and how these may contribute to integrated care of mental health and illness. The program featured numerous tracks and subtracks in areas of interest such as addiction psychiatry, child, adolescent and geriatric psychiatry, and psychosomatic medicine. PMID- 26261852 TI - American Diabetes Association - 75th Scientific Sessions (June 5-9, 2015 - Boston, Massachusetts, USA). AB - The 75th American Diabetes Association (ADA) Scientific Sessions, brought together experts in the diabetes research field to hear hundreds of oral presentations and thousands of poster presentations discussing novel research findings related to diabetes, obesity, fatty liver disease and related medical conditions. A significant number of presentations considered experimental and investigational therapeutic candidates that will potentially aid in the fight against diabetes, which continues to be on the increase worldwide. PMID- 26261853 TI - The European League Against Rheumatism (EULAR) - 16th Annual European Congress (June 10-13, 2015 - Rome, Italy). AB - The 16th Annual European Congress of Rheumatology, organized by the European League Against Rheumatism (EULAR), provided the latest advances in the field of rheumatologic diseases to around 14,000 participants from more than 120 countries. This congress has become the primary platform for exchange of scientific and clinical information and the biggest rheumatology event in Europe. The congress covered a broad spectrum of the rheumatic diseases through 400 lectures, workshops, 300 oral presentations, 2,000 posters, 350 invited speakers, and basic science and clinical symposia. PMID- 26261854 TI - Anti-angiogenic nanotherapy via active targeting systems to tumors and adipose tissue vasculature. AB - Sophisticated drug delivery systems (DDS) are required for delivering drugs, especially macromolecules such as nucleic acids or proteins, to their sites of action. Therefore it is a prerequisite that future DDS are designed to selectively target a tissue. In this review, we focus on systems that actively target the vasculature in tumors or adipose tissues. For targeting tumor vasculatur, a new strategy referred to as dual-targeting is proposed that uses a combination of a receptor specific ligand and a cell penetrating peptide, which can induce the synergistic enhancement of tissue selectivity under in vivo conditions. A novel pH-sensitive cationic lipid was designed to enhance the endosomal release of encapsulated compounds such as siRNA as well as to improve the stability in blood circulation after intravenous administration. A cyclic RGD peptide is used as an active targeting ligand. For targeting adipose vasculature, prohibitin, which is expressed on the surface of adipose endothelial cells, was targeted with KGGRAKD peptides on the surface of PEGylated nanoparticles. Prohibitin targeted nanoparticles (PTNP) encapsulating Cytochrome c (CytC) can selectively target adipose vasculature by optimizing the lengths of the PEG linkers and can deliver CytC to adipose endothelial cells. PTNP can successfully induce anti-obese effects as well as apoptosis by delivering CytC to the cytosol in endothelial cells. Unexpectedly, the EPR (enhanced permeability and retention) effect, which is usually observed in tumor tissue, was also observed in the adipose vasculature, especially in obese mice, where PEGylated nanoparticles can pass through the endothelial barriers in adipose tissue. We believe that these achievements in active targeting will allow a greatly expanded use of DDS for nanomedicines. PMID- 26261855 TI - Tunable coverage of immobilized biomolecules for biofunctional interface design. AB - The controlled coverage of immobilized biomolecules is introduced, illustrating a concept for designing biomaterial surfaces such that the extent of manipulation employed to elicit biological responses is controlled according to density changes in the underlying chemical motifs and the density of immobilized biomolecules. PMID- 26261856 TI - Cellular effects of magnetic nanoparticles explored by atomic force microscopy. AB - The investigation of subtle change of cells exposed to nanomaterials is extremely essential but also challenging for nanomaterial-based biological applications. In this study, atomic force microscopy (AFM) was employed to investigate the effects of iron-iron oxide core-shell magnetic nanoparticles on the mechanical properties of bovine articular chondrocytes (BACs). After being exposed to the nanoparticles even at a high nanoparticle-concentration (50 MUg mL(-1)), no obvious difference was observed by using conventional methods, including the WST-1 assay and live/dead staining. However a significant difference of Young's modulus of the cells was detected by AFM even when the concentration of nanoparticles applied in the cell culture medium was low (10 MUg mL(-1)). The difference of cellular Young's modulus increased with the increase of nanoparticle concentration. AFM was demonstrated to be a useful tool to identify the subtle change of cells when they were exposed to nanomaterials even at a low concentration. PMID- 26261857 TI - Priming cells for their final destination: microenvironment controlled cell culture by a modular ECM-mimicking feeder film. AB - Mammalian cell culture is the starting point in many research studies focusing on biomedical applications. However, researchers have little control over the standardized cell microenvironment parameters. Here a modular ECM-mimicking surface coating for cell culture environment is designed. This substrate is a new and versatile thin film obtained by spin-coating of concentrated gelatin crosslinked by transglutaminase. It can be modified with respect to the biochemical and biophysical needs of the final cell destination, i.e. it delivers loaded multi-growth factors and serum components and allows for cell culture in a serum-free culture medium. Also, a well-known cell behavior modulator, the substrate stiffness, is controlled exogenously by addition of nanoparticles. In addition to growth factors, antimicrobial agents such as natural peptides are added to the substrate for limiting the repeated addition of antimicrobial agents to the culture medium and to prevent the increase of resistant bacterial strains in the culture environment. Finally, this substrate contains simultaneously ECM components, growth factors, stiffening elements and antimicrobial agents. It provides a favorable microenvironment and sterile conditions. It is a free-of maintenance system, as cells will grow without addition of serum or antimicrobial cocktails. This low cost and easy-to-use substrate could emerge as a new standard for cell culture. PMID- 26261858 TI - Letter Concerning: "Genotyping for Kidd, Kell, Duffy, Scianna, and RHCE Blood Group Antigens Polymorphisms in Jiangsu Chinese Han". Authors' Reply. PMID- 26261859 TI - [Abstracts from the VI International Congress ADELF-EPIRER, September 10-12, 2014, Nice, France]. PMID- 26261860 TI - From the Editor: Artificial intelligence in life science. PMID- 26261861 TI - [Abstracts from the XXVIII National Congress, March 26-27, 2015, Nancy, France]. PMID- 26261862 TI - [Reply]. PMID- 26261863 TI - A molecular dynamics study of Beta-Glucosidase B upon small substrate binding. AB - Paenibacillus polymyxa beta-glucosidase B (BglB), belongs to a GH family 1, is a monomeric enzyme that acts as an exo-beta-glucosidase hydrolysing cellobiose and cellodextrins of higher degree of polymerization using retaining mechanism. A molecular dynamics (MD) simulation was performed at 300 K under periodic boundary condition for 5 ns using the complexes structure obtained from previous docking study, namely BglB-Beta-d-glucose and BglB-Cellobiose. From the root-mean-square deviation analysis, both enzyme complexes were reported to deviate from the initial structure in the early part of the simulation but it was stable afterwards. The root-mean-square fluctuation analysis revealed that the most flexible regions comprised of the residues from 26 to 29, 43 to 53, 272 to 276, 306 to 325 and 364 to 367. The radius of gyration analysis had shown the structure of BglB without substrate became more compact towards the end of the simulation compare to other two complexes. The residues His122 and Trp410 were observed to form stable hydrogen bond with occupancy higher than 10%. In conclusion, the behaviour of BglB enzyme towards the substrate binding was successfully explored via MD simulation approaches. PMID- 26261864 TI - Attachment disorganization among children in Neonatal Intensive Care Unit: Preliminary results. AB - BACKGROUND: Preterm children have been reported to be at higher risk to develop attachment insecurity. AIMS: The present study aimed to investigate potential differences in attachment security between newborns who were sent to Neonatal Intensive Care Unit (NICU) and those who were not, in a population of full-term children. STUDY DESIGN: Participants (162 mother-child dyads) were part of a longitudinal study (MAVAN). Twenty-three of these children received special care at birth (NICU group). Attachment security was assessed at 36 months with the Strange Situation Procedure. Socio-economic status (SES), birth weight, maternal mood, maternal sensitivity, mental/psychomotor developmental indexes, Apgar scores, presence of complications during delivery and infant general health were assessed. RESULTS: In the No-NICU group, 55.4% of children were securely attached, 24.5% were insecure and 20.1% were disorganized. However, in the NICU group, 43.5% of children were securely attached, 8.7% were insecure and 47.8% were disorganized (chi(2)=9.0; p=.01). The only differences between the 2 groups were a lower Apgar, more respiratory infections and more visits to walk-in clinic/hospital (p's<.05) and a trend for lower SES and more ear infections in the NICU group. Logistic regressions revealed an odds ratio of 6.1 (p=.003) of developing a disorganized attachment after a stay in NICU, when controlling for these confounding variables. CONCLUSION: Newborns who were admitted to NICU have an odds ratio of about 6 to develop a disorganized attachment at 36 months. These preliminary results support the importance of supportive parental proximity and contact with the infant in the NICU and possible after-care. PMID- 26261865 TI - Favourable outcome of long-term combined psychotherapy for patients with borderline personality disorder: Six-year follow-up of a randomized study. AB - OBJECTIVE: This study reports the six-year follow-up data of patients with borderline personality disorder (BPD) who participated in the Ulleval Personality Project (UPP), a randomized clinical study comparing outpatient individual psychotherapy (OIP) with a long-term combination programme (CP) comprising short term day-hospital treatment followed by outpatient combined group and individual psychotherapy. METHODS: For 52 patients, outcomes were evaluated after 8 months, 18 months, 3 years, and 6 years based on a wide range of clinical measures, such as symptom severity, psychosocial functioning, personality functioning, and Axis I and II diagnoses. RESULTS: At the six-year follow-up, patients in the CP condition reported significantly greater reduction of symptom distress and improvements in the personality functioning domains Identity Integration and Self control compared with patients allocated to OIP. Patients in the CP also had a more favourable long-term course of psychosocial functioning. There were no differences between treatment conditions in outcomes of interpersonal functioning and self-esteem. CONCLUSIONS: Long-term psychotherapy in a combination programme seems favourable for BPD patients. In this study, patients who received combined treatment fared better on crucial parameters than patients who received individual therapy. Of particular importance are the positive effects on fundamental borderline problem areas like Identity Integration and Self-control. PMID- 26261866 TI - N-Nitrosodimethylamine formation from ozonation of chlorpheniramine: Influencing factors and transformation mechanism. AB - As a disinfection byproduct, the detection of N-nitrosodimethylamine (NDMA) in aquatic environments across the globe has caused widespread concern due to its potential carcinogenicity. In this study, the possibility of NDMA formation from chlorpheniramine ozonation was investigated. The influencing factors including the initial chlorpheniramine concentration, ozone dose, pH, and water matrix were quantified. Furthermore, the mechanisms for chlorpheniramine transformation and NDMA formation were explored. Our results demonstrate that ozonation is effective in removing chlorpheniramine. Generation of dimethylamine (DMA) and NDMA was observed during chlorpheniramine ozonation. Higher initial chlorpheniramine concentration and ozone dose resulted in higher production of NDMA. Acidic conditions (pH<=5) did not facilitate the production of NDMA. Ozone molecules played a dominant role in chlorpheniramine degradation, and influenced DMA release and NDMA formation. DMA and NDMA generations as well as their degradations were mainly attributed to hydroxyl radicals (.OH) produced by ozone decomposition. Water matrix properties such as HCO3(-) and humic acid affected DMA and NDMA generation due to .OH competition. The degradation intermediates of chlorpheniramine were identified, among which only the intermediates with a DMA group were attributable to NDMA formation. A possible pathway for NDMA formation from chlorpheniramine ozonation is proposed. PMID- 26261867 TI - Flexible Graphene Field-Effect Transistors Encapsulated in Hexagonal Boron Nitride. AB - Flexible graphene field-effect transistors (GFETs) are fabricated with graphene channels fully encapsulated in hexagonal boron nitride (hBN) implementing a self aligned fabrication scheme. Flexible GFETs fabricated with channel lengths of 2 MUm demonstrate exceptional room-temperature carrier mobility (MUFE = 10 000 cm(2) V(-1) s(-1)), strong current saturation characteristics (peak output resistance, r0 = 2000 Omega), and high mechanical flexibility (strain limits of 1%). These values of MUFE and r0 are unprecedented in flexible GFETs. Flexible radio frequency FETs (RF-FETs) with channel lengths of 375 nm demonstrate MUFE = 2200 cm(2) V(-1) s(-1) and r0 = 132.5 Omega. Unity-current gain frequencies, fT, and unity-power gain frequencies, fmax, reach 12.0 and 10.6 GHz, respectively. The corresponding ratio of cutoff frequencies approaches unity (fmax/fT = 0.9), a record value for flexible GFETs. Intrinsic fT and fmax are 29.7 and 15.7 GHz, respectively. The outstanding electronic characteristics are attributed to the improved dielectric environment provided by full hBN encapsulation of the graphene channel in conjunction with an optimized, self-aligned device structure. These results establish hBN as a mechanically robust dielectric that can yield enhanced electronic characteristics to a diverse array of graphene-based flexible electronics. PMID- 26261868 TI - Treatment of tinnitus. AB - PURPOSE OF REVIEW: Tinnitus, the perception of sound in the absence of a corresponding external acoustic stimulus, is a highly prevalent and frequently severely impairing disorder with worldwide impact. In this article after a short overview about epidemiology and pathophysiology the currently available treatment options will be discussed with specific consideration of the available evidence, their mechanisms of action and their limitations. RECENT FINDINGS: During the last decades, advances in neuroimaging methods and the development of animal models have contributed to an increasing understanding of the neuronal correlates of tinnitus and have motivated the development of innovative brain-based treatment approaches for directly targeting the neuronal correlates of tinnitus. A further important development has been the insight that there exist different forms of tinnitus that differ in their pathophysiology and their response to specific treatments. SUMMARY: Treatment of tinnitus should be based on a comprehensive diagnosis of etiologic and concomitant aspects of an individual's tinnitus. Already today a large variety of therapeutic interventions are available, which can efficiently reduce tinnitus severity. Several innovative treatment approaches are currently under development. PMID- 26261869 TI - Vitamin D deficiency is common in HIV-infected southern Australian adults. AB - BACKGROUND: Vitamin D deficiency can have serious health consequences and may be particularly important for those living with HIV. It is unknown whether HIV infection is a risk factor for vitamin D deficiency. The aim of the study was to determine whether vitamin D deficiency is more common in HIV-infected than in HIV uninfected individuals. METHODS: This was a cross-sectional study of HIV-infected and uninfected individuals. A total of 997 HIV-infected participants were from a sexual health clinic in Melbourne with 25(OH)D measurements taken between 2008 and 2012. 3,653 HIV-uninfected individuals were participants in a statewide Victorian survey with 25(OH)D measurements taken between 2009 and 2010. Logistic regression models evaluated the association of HIV status with vitamin D deficiency (25[OH]D<50 nmol/l). RESULTS: The frequency of vitamin D deficiency was significantly more common in HIV-infected (39% [95% CI 36%, 42%]) compared with HIV-uninfected individuals 23% (95% CI 15%, 31%). In multivariable analysis, males (adjusted odds ratio [aOR] 0.8; 95% CI 0.6, 0.9; P=0.001), Caucasian country of origin (aOR 0.4; 95% CI 0.3, 0.4; P<0.001), summer/autumn (aOR for autumn 0.2; 95% CI 0.1, 0.3; P<0.001), total cholesterol to high-density lipoprotein ratio >5 (aOR 1.4; 95% CI 1.2, 1.8; P<0.001) and HIV infection (aOR 1.7; 95% CI 1.4, 2.1; P<0.001) were associated with vitamin D deficiency. CONCLUSIONS: Adults living in southern Australia with HIV were more likely to be vitamin D deficient than the general population. PMID- 26261870 TI - CD55, CD59, factor H and factor H-like 1 gene expression analysis in tumors of the ovary and corpus uteri origin. AB - The expression level of complement regulators in ovarian and corpus uteri tumors was not fully established so far. In current manuscript we performed gene expression analysis by the real-time PCR approach to investigate both membrane bound - CD55 and CD59 and fluid phase - factor H and factor H-like 1 complement regulators. We found increased CD55 expression in corpus uteri tumors when compared to control tissues, whereas in ovarian cancer CD55 expression was lower than in control sections. Additionally we found CD59 expression to be more prominent in ovarian cancer than in corpus uteri tumor samples. We observed also the strong positive correlation between the level of expression of the whole group of regulators, which was particularly significant between the expression of factor H and factor H- like 1. In conclusion we present novel results which implicates different role of particular complement inhibitors in the regulation of the complement system in two cancer types examined. Strong positive correlation between examined proteins implicates similar pattern of the regulation which should be taken into consideration with regards to the possible immunotherapy applied as adjuvant therapeutic approach in these two indications. The inhibition of complement regulation may serve as a strategy to potentiate the efficacy of such treatment. PMID- 26261871 TI - Neurogenic Ovarian Cyst--A Rare, Monodermal Teratoma. PMID- 26261872 TI - Artificial Ligands of Streptavidin (ALiS): Discovery, Characterization, and Application for Reversible Control of Intracellular Protein Transport. AB - Artificial ligands of streptavidin (ALiS) with association constants of ~10(6) M( 1) were discovered by high-throughput screening of our chemical library, and their binding characteristics, including X-ray crystal structure of the streptavidin complex, were determined. Unlike biotin and its derivatives, ALiS exhibits fast dissociation kinetics and excellent cell permeability. The streptavidin-ALiS system provides a novel, practical compound-dependent methodology for repeated reversible cycling of protein localization between intracellular organella. PMID- 26261873 TI - Architecture of GnRH-Gonadotrope-Vasculature Reveals a Dual Mode of Gonadotropin Regulation in Fish. AB - The function and components of the hypothalamic-pituitary axis are conserved among vertebrates; however, in fish, a neuroglandular mode of delivery (direct contact between axons and endocrine cells) was considered dominant, whereas in tetrapods hypothalamic signals are relayed to their targets via the hypophysial portal blood system (neurovascular delivery mode). By using a transgenic zebrafish model we studied the functional and anatomical aspects of gonadotrope regulation thus revisiting the existing model. FSH cells were found to be situated close to the vasculature whereas the compact organization of LH cells prevented direct contact of all cells with the circulation. GnRH3 fibers formed multiple boutons upon reaching the pituitary, but most of these structures were located in the neurohypophysis rather than adjacent to gonadotropes. A close association was observed between FSH cells and GnRH3 boutons, but only a fifth of the LH cells were in direct contact with GnRH3 axons, suggesting that FSH cells are more directly regulated than LH cells. GnRH3 fibers closely followed the vasculature in the neurohypophysis and formed numerous boutons along these tracts. These vessels were found to be permeable to relatively large molecules, suggesting the uptake of GnRH3 peptides. Our findings have important implications regarding the differential regulation of LH and FSH and contradict the accepted notion that fish pituitary cells are mostly regulated directly by hypothalamic fibers. Instead, we provide evidence that zebrafish apply a dual mode of gonadotrope regulation by GnRH3 that combines both neuroglandular and neurovascular components. PMID- 26261875 TI - Synthesis of N-Aryl-3,5-dichloro-4H-1,2,6-thiadiazin-4-imines from 3,4,4,5 Tetrachloro-4H-1,2,6-thiadiazine. AB - Condensation of 3,4,4,5-tetrachloro-4H-1,2,6-thiadiazine with a range of anilines gave 22 N-aryl-3,5-dichloro-4H-1,2,6-thiadiazin-4-imines in 43-96% yields. The scope and limitations of this condensation are briefly investigated. Furthermore, mono- and bis-substitution of the C-3 and C-5 chlorines of 3,5-dichloro-N-phenyl 4H-1,2,6-thiadiazin-4-imine by amine and alkoxide nucleophiles is explored. Finally, Stille coupling chemistry is used to prepare several N-phenyl-3,5-diaryl 4H-1,2,6-thiadiazin-4-imines. PMID- 26261876 TI - Highly Efficient Solar Water Splitting from Transferred TiO2 Nanotube Arrays. AB - We report a synergistic effect of flame and chemical reduction methods to maximize the efficiency of solar water splitting in transferred TiO2 nanotube (TNT) arrays on a transparent conducting oxide (TCO) substrate. The flame reduction method (>1000 degrees C) leads to few oxygen vacancies in the anatase TNT arrays, but it exhibits unique advantages for excellent interfacial characteristics between transferred TNT arrays and TCO substrates, which subsequently induce a cathodic on-set potential shift and sharp photocurrent evolution. By contrast, the employed chemical reduction method for TNT arrays/TCO gives rise to an abrupt increase in photocurrent density, which results from the efficient formation of oxygen vacancies in the anatase TiO2 phase, but a decrease in charge transport efficiency with increasing chemical reduction time. We show that flame reduction followed by chemical reduction could significantly improve the saturation photocurrent density and interfacial property of TNT arrays/TCO photoanodes simultaneously without mechanical fracture via the synergistic effects of coreducing methods. PMID- 26261877 TI - NanoCluster Beacons Enable Detection of a Single N6-Methyladenine. AB - While N(6)-methyladenine (m(6)A) is a common modification in prokaryotic and lower eukaryotic genomes and has many biological functions, there is no simple and cost-effective way to identify a single N(6)-methyladenine in a nucleic acid target. Here we introduce a robust, simple, enzyme-free and hybridization-based method using a new silver cluster probe, termed methyladenine-specific NanoCluster Beacon (maNCB), which can detect single m(6)A in DNA targets based on the fluorescence emission spectra of silver clusters. Not only can maNCB identify m(6)A at the single-base level but it also can quantify the extent of adenine methylation in heterogeneous samples. Our method is superior to high-resolution melting analysis as we can pinpoint the location of m(6)A in the target. PMID- 26261878 TI - Warmer winters modulate life history and energy storage but do not affect sensitivity to a widespread pesticide in an aquatic insect. AB - Despite the increased attention for the effects of pesticides under global warming no studies tested how winter warming affects subsequent sensitivity to pesticides. Winter warming is expected to cause delayed negative effects when it increases metabolic rates and thereby depletes energy reserves. Using a common garden experiment, we investigated the combined effect of a 4 degrees C increase in winter temperature and subsequent exposure to chlorpyrifos in the aquatic larvae of replicated low- and high-latitude European populations of the damselfly Ischnura elegans. The warmer winter (8 degrees C) resulted in a higher winter survival and higher growth rates compared to the cold winter (4 degrees C) commonly experienced by European high-latitude populations. Low-latitude populations were better at coping with the warmer winter, indicating thermal adaptation to the local winter temperatures. Subsequent chlorpyrifos exposure at 20 degrees C induced strong negative effects on survival, growth rate, lipid content and acetylcholinesterase activity while phenoloxidase activity increased. These pesticide effects were not affected by winter warming. Our results suggest that for species where winter warming has positive effects on life history, no delayed effects on the sensitivity to subsequent pesticide exposure should be expected. PMID- 26261879 TI - Dietary ingestion of fine sediments and microalgae represent the dominant route of exposure and metal accumulation for Sydney rock oyster (Saccostrea glomerata): A biokinetic model for zinc. AB - Past studies disagree on the extent to which dissolved or dietary uptake contribute to metal bioaccumulation in the filter-feeding Sydney rock oyster (Saccostrea glomerata) in urbanized estuaries. Although most data support the assumption that fine sediments are a major route of metal uptake in these bivalves, some studies based in the Sydney estuary, Australia, have indicated a poor correlation. In the present study, seawater, sediment and microalgae were radiolabelled with (65)Zn tracer and exposed to S. glomerata to assess the influence of dissolved and dietary sources to Zn bioaccumulation. Oysters in the dissolved-phase uptake experiment (5, 25 and 50 MUg L(-1) (65)Zn for 4 d followed by 21 days of depuration) readily accumulated (65)Zn for all three concentrations with an uptake rate constant of 0.160+/-0.006 L dry weight g(-1) d(-1). Oysters in the dietary assimilation experiment (1h pulse-feed of either (65)Zn radiolabelled suspended fine-fraction (<63 MUm) sediment or the microalgae Tetraselmis sp.) accumulated (65)Zn, with assimilation efficiencies of 59 and 67% for fine sediment and microalgae, respectively. The efflux rates were low for the three experiments (0.1-0.5% d(-1)). A bioaccumulation kinetic model predicts that uptake of Zn will occur predominantly through the dietary ingestion of contaminated fine sediment particles and microalgae within the water column, with considerably greater metal bioaccumulation predicted if oysters ingested microalgae preferentially to sediments. However, the model predicts that for dissolved Zn concentrations greater than 40 MUg L(-1), as observed during precipitation events, the uptake of the dissolved phase may contribute >=50% to accumulation. Overall, the results of the present study suggest that all three sources may be important exposure routes to S. glomerata under different environmental conditions, but contributions from dietary exposure will often dominate. PMID- 26261880 TI - The biological effects of ionising radiation on Crustaceans: A review. AB - Historic approaches to radiation protection are founded on the conjecture that measures to safeguard humans are adequate to protect non-human organisms. This view is disparate with other toxicants wherein well-developed frameworks exist to minimise exposure of biota. Significant data gaps for many organisms, coupled with high profile nuclear incidents such as Chernobyl and Fukushima, have prompted the re-evaluation of our approach toward environmental radioprotection. Elucidating the impacts of radiation on biota has been identified as priority area for future research within both scientific and regulatory communities. The crustaceans are ubiquitous in aquatic ecosystems, comprising greater than 66,000 species of ecological and commercial importance. This paper aims to assess the available literature of radiation-induced effects within this subphylum and identify knowledge gaps. A literature search was conducted pertaining to radiation effects on four endpoints as stipulated by a number of regulatory bodies: mortality, morbidity, reproduction and mutation. A major finding of this review was the paucity of data regarding the effects of environmentally relevant radiation doses on crustacean biology. Extremely few studies utilising chronic exposure durations or wild populations were found across all four endpoints. The dose levels at which effects occur was found to vary by orders of magnitude thus presenting difficulties in developing phyla-specific benchmark values and reference levels for radioprotection. Based on the limited data, mutation was found to be the most sensitive endpoint of radiation exposure, with mortality the least sensitive. Current phyla-specific dose levels and limits proposed by major regulatory bodies were found to be inadequate to protect species across a range of endpoints including morbidity, mutation and reproduction and examples are discussed within. These findings serve to prioritise areas for future research that will significantly advance understanding of radiation-induced effects in aquatic invertebrates and consequently enhance ability to predict the impacts of radioactive releases on the environment. PMID- 26261883 TI - Commentary: Endotracheal Tube Electrodes to Assess Vocal Cord Motor Function During Surgery in the Cerebellopontine Angle. PMID- 26261881 TI - Transferrin-mediated iron sequestration as a novel therapy for bacterial and fungal infections. AB - Pathogenic microbes must acquire essential nutrients, including iron, from the host in order to proliferate and cause infections. Iron sequestration is an ancient host antimicrobial strategy. Thus, enhancing iron sequestration is a promising, novel anti-infective strategy. Unfortunately, small molecule iron chelators have proven difficult to develop as anti-infective treatments, in part due to unacceptable toxicities. Iron sequestration in mammals is predominantly mediated by the transferrin family of iron-binding proteins. In this review, we explore the possibility of administering supraphysiological levels of exogenous transferrin as an iron sequestering therapy for infections, which could overcome some of the problems associated with small molecule chelation. Recent studies suggest that transferrin delivery may represent a promising approach to augment both natural resistance and traditional antibiotic therapy. PMID- 26261884 TI - Functional genomics indicate that schizophrenia may be an adult vascular-ischemic disorder. AB - In search for the elusive schizophrenia pathway, candidate genes for the disorder from a discovery sample were localized within the energy-delivering and ischemia protection pathway. To test the adult vascular-ischemic (AVIH) and the competing neurodevelopmental hypothesis (NDH), functional genomic analyses of practically all available schizophrenia-associated genes from candidate gene, genome-wide association and postmortem expression studies were performed. Our results indicate a significant overrepresentation of genes involved in vascular function (P < 0.001), vasoregulation (that is, perivascular (P < 0.001) and shear stress (P < 0.01), cerebral ischemia (P < 0.001), neurodevelopment (P < 0.001) and postischemic repair (P < 0.001) among schizophrenia-associated genes from genetic association studies. These findings support both the NDH and the AVIH. The genes from postmortem studies showed an upregulation of vascular-ischemic genes (P = 0.020) combined with downregulated synaptic (P = 0.005) genes, and ND/repair (P = 0.003) genes. Evidence for the AVIH and the NDH is critically discussed. We conclude that schizophrenia is probably a mild adult vascular-ischemic and postischemic repair disorder. Adult postischemic repair involves ND genes for adult neurogenesis, synaptic plasticity, glutamate and increased long-term potentiation of excitatory neurotransmission (i-LTP). Schizophrenia might be caused by the cerebral analog of microvascular angina. PMID- 26261885 TI - Atypical spatiotemporal signatures of working memory brain processes in autism. AB - Working memory (WM) impairments may contribute to the profound behavioural manifestations in children with autism spectrum disorder (ASD). However, previous behavioural results are discrepant as are the few functional magnetic resonance imaging (fMRI) results collected in adults and adolescents with ASD. Here we investigate the precise temporal dynamics of WM-related brain activity using magnetoencephalography (MEG) in 20 children with ASD and matched controls during an n-back WM task across different load levels (1-back vs 2-back). Although behavioural results were similar between ASD and typically developing (TD) children, the between-group comparison performed on functional brain activity showed atypical WM-related brain processes in children with ASD compared with TD children. These atypical responses were observed in the ASD group from 200 to 600 ms post stimulus in both the low- (1-back) and high- (2-back) memory load conditions. During the 1-back condition, children with ASD showed reduced WM related activations in the right hippocampus and the cingulate gyrus compared with TD children who showed more activation in the left dorso-lateral prefrontal cortex and the insulae. In the 2-back condition, children with ASD showed less activity in the left insula and midcingulate gyrus and more activity in the left precuneus than TD children. In addition, reduced activity in the anterior cingulate cortex was correlated with symptom severity in children with ASD. Thus, this MEG study identified the precise timing and sources of atypical WM-related activity in frontal, temporal and parietal regions in children with ASD. The potential impacts of such atypicalities on social deficits of autism are discussed. PMID- 26261887 TI - Implementation of Mental Health Huddles on Dementia Care Units. AB - Client-responsive behaviours occur commonly among residents in long-term care (LTC) settings; direct-care staff, however, receive little education, support, or opportunities to discuss and collaborate on managing such behaviours. Our participatory action project introduced mental health huddles to support staff in discussing and managing client-responsive behaviours in long-term care. This research project engaged direct-care staff (e.g., personal support workers, registered practical nurses, housekeeping staff, and registered nurses) in learning how to use these huddles. Staff workers used huddles as a forum to stay informed, review work, problem solve, and develop person-centered action plans. Fifty-six huddles occurred over a 12-week period; two to seven direct-care staff participated in each huddle. Focus groups indicated improved staff collaboration, teamwork, support, and communication when discussing specific responsive behaviours. Huddles provided LTC staff with the opportunity to collaborate and discuss strategies to optimize resident care. Further research on how huddles affect resident care outcomes is needed. PMID- 26261886 TI - Lack of association between type 2 diabetes and major depression: epidemiologic and genetic evidence in a multiethnic population. AB - The positive association between depression and type 2 diabetes (T2D) has been controversial, and little is known about the molecular determinants linking these disorders. Here we investigated the association between T2D and depression at the clinical and genetic level in a multiethnic cohort. We studied 17,404 individuals from EpiDREAM (3209 depression cases and 14,195 controls) who were at risk for T2D and had both phenotypic and genotypic information available at baseline. The glycemic status was determined using the 2003 American Diabetes Association criteria and an oral glucose tolerance test. Major depressive episode during the previous 12 months was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnostic criteria. Twenty single-nucleotide polymorphisms (SNPs) previously associated with T2D were genotyped using the cardiovascular gene-centric 50-K SNP array and were analyzed separately and in combination using an unweighted genotype score (GS). Multivariate logistic regression models adjusted for age, sex, ethnicity and body mass index were performed. Newly diagnosed impaired fasting glucose (IFG)/impaired glucose tolerance (IGT), T2D and dysglycemia status were not associated with major depression (0.30 ? P ? 0.65). Twelve out of twenty SNPs and the GS were associated with IFG/IGT, T2D and/or dysglycemia status (6.0 * 10(-35) ? P ? 0.048). In contrast, the 20 SNPs and GS were not associated with depression (P ? 0.09). Our cross-sectional data do not support an association between T2D and depression at the clinical and genetic level in a multiethnic population at risk for T2D. PMID- 26261888 TI - Analyzing the Interprofessional Working of a Home-Based Primary Care Team. AB - Increasingly, interprofessional teams are responsible for providing integrated health care services. Effective teams, however, are not the result of chance but require careful planning and ongoing attention to team processes. Based on a case study involving interviews, participant observation, and a survey, we identified key attributes for effective interprofessional working (IPW) within a home-based primary care (HBPC) setting. Recognizing the importance of a theoretical model that reflects the multidimensional nature of team effectiveness research, we employed the integrated team effectiveness model to analyze our findings. The results indicated that a shared vision, common goals, respect, and trust among team members - as well as processes for ongoing communication, effective leadership, and mechanisms for conflict resolution - are vital in the development of a high-functioning IPW team. The ambiguity and uncertainty surrounding the context of service provision (clients' homes), as well the negotiation of external relationships in the HBPC field, require further investigation. PMID- 26261889 TI - Statistical Considerations in Clinical Trial Design of Immunotherapeutic Cancer Agents. AB - The classical model for identification and clinical development of anticancer agents was based on small molecules, which were often quite toxic. Early studies in small groups of patients would seek to identify a maximum tolerated dose and major dose-limiting toxicities. Tumor response (shrinkage) would be assessed after a minimum number of doses in phase II testing. The decision to take the drug into the randomized phase III clinical setting was usually based on the proportion and duration of objective tumor responses, along with overall survival compared with historical controls. Immune-oncologics that are designed to fight cancer by direct CD8(+) T-cell priming and activation or by blocking a negative regulatory molecule have a number of sharp distinctions from cytotoxic drugs. These include cytoreductive effects that may be very different in timing of onset from traditional chemotherapy and the potential for inducing long-term durable remissions even in heavily pretreated patients with metastatic disease. In this paper we review the different classes of immune-oncologic drugs in clinical development with particular attention to the biostatistical challenges associated with evaluating efficacy in clinical trials. Confronting these issues upfront is particularly important given the rapidly expanding number of clinical trials with both monotherapy and combination trials in immunooncology. PMID- 26261890 TI - Identification of a Novel Immunodominant HLA-B*07: 02-restricted Adenoviral Peptide Epitope and Its Potential in Adoptive Transfer Immunotherapy. AB - Adenovirus infections of immunocompromised patients, particularly following allogeneic hematopoietic stem cell transplantation, are associated with morbidity and mortality. Immunotherapy by adoptive transfer of hexon-specific and penton specific T cells has been successfully applied, but many approaches are impeded by the low number of HLA class I-restricted adenoviral peptide epitopes described to date. We use a novel method to identify naturally presented adenoviral peptide epitopes from infected human cells, ectopically expressing defined HLA, using peptide elution and liquid chromatography-mass spectrometry analysis. We show that the previously described HLA-A*01:01-restricted peptide epitope LTDLGQNLLY from hexon protein is naturally presented, and demonstrate the functionality of LTDLGQNLLY-specific T cells. We further identify a novel immunodominant HLA B*07:02-restricted peptide epitope VPATGRTLVL from protein 13.6 K, and demonstrate the high proliferative, cytotoxic, and IFN-gamma-producing capacity of peptide-specific T cells. Lastly, LTDLGQNLLY-specific T cells can be detected ex vivo following adoptive transfer therapy, and LTDLGQNLLY-specific and VPATGRTLVL-specific T cells have memory phenotypes ex vivo. Given their proliferative and cytotoxic capacity, such epitope-specific T cells are promising candidates for adoptive T-cell transfer therapy of adenovirus infection. PMID- 26261891 TI - A Fixed Human Umbilical Vein Endothelial Cell Vaccine With 2 Tandem Repeats of Microbial HSP70 Peptide Epitope 407-426 As Adjuvant for Therapy of Hepatoma in Mice. AB - Various studies have indicated that vaccination with endothelial cells targeting tumor angiogenesis is an effective approach for inhibiting tumor growth and metastasis. However, our previous study about a viable human umbilical vein endothelial cell (HUVEC) vaccine demonstrated that the antitumor efficiency of the targeted therapy using HUVEC plus appropriate adjuvant is feasible but need further optimization. In this study, glutaraldehyde-fixed HUVEC, tested as another antigen form, was conjugated with 2 repeats of mycobacterial HSP70(407 426) (M2) to prepare a novel HUVEC-M2 vaccine, which was expected to have an enhanced antitumor efficacy. HUVEC-M2 was administrated in mice by subcutaneous immunization in both prophylactic and therapeutic procedures. Compared with HUVEC alone, HUVEC-M2 induced a more significant inhibition on the growth of H22 hepatocellular carcinoma in mice and prolonged the survival of H22 hepatocellular carcinoma-bearing mice in both prophylactic and therapeutic procedures. Meanwhile, specific CTLs as well as antibodies against tumor endothelium correlated well with the inhibition effect were evoked by HUVEC-M2, which indicated that antiangiogenesis was mainly responsible for the antitumor effect. Moreover, the attenuated tumor-induced angiogenesis in intradermal tumor model and reduced vessel density of the intradermal tumor in mice further confirmed the antiangiogenesis effect elicited by HUVEC-M2. All the data suggested that M2 could be used as a potent adjuvant to conjugate with glutaraldehyde-fixed HUVEC for preparing HUVEC vaccines and would have important clinical implications for adjuvant cancer therapy. PMID- 26261892 TI - Identification of Programmed Death Ligand 1-derived Peptides Capable of Inducing Cancer-reactive Cytotoxic T Lymphocytes From HLA-A24+ Patients With Renal Cell Carcinoma. AB - Molecular therapy targeting tumor angiogenesis has been the standard treatment for metastatic renal cell carcinoma (mRCC). However, despite their significant antitumor effects, most of patients with mRCC have not been cured. Under such circumstances, anticancer immunotherapy has been considered a promising treatment modality for mRCC, and cancer-reactive cytotoxic T lymphocytes (CTLs) are the most powerful effectors among several immune cells. However, anticancer CTLs can be inhibited by several immune inhibitory mechanisms, including the interaction between programmed death 1 (PD-1) and its ligand PD-L1, on T cells and cancer cells, respectively. Alternatively, this also means that PD-L1 could be a promising target for anticancer immunotherapy. Therefore, we searched for PD-L1 derived peptides that are applicable for anticancer vaccine for HLA-A24(+) RCC patients. Among 5 peptides derived from PD-L1, which were prepared based on the binding motif to the HLA-A24(+) allele, both PD-L1(11-19) and PD-L1(41-50) peptides induced peptide-specific CTLs from peripheral blood mononuclear cells of HLA-A24(+) RCC patients. Such PD-L1 peptide-stimulated CD8 T cells showed cytotoxicity against HLA-A24(+) and PD-L1-expressing RCC cells. Although IFN gamma treatment increased PD-L1 expression on PD-L1(low) RCC cells, their sensitivity to cytotoxicity of PD-L1 peptide-stimulated CD8(+) T cells varied between patients. Altogether, these results indicate that both PD-L1(11-19) and PD-L1(41-50) peptides could be candidates for peptide-based anticancer vaccines for HLA-A24(+) mRCC patients. PMID- 26261893 TI - Reprogramming Immune Response With Capsid-Optimized AAV6 Vectors for Immunotherapy of Cancer. AB - In the current studies we generated novel capsid-optimized adeno-associated virus (AAV) serotype 6 (AAV6) vectors expressing a tumor-associated antigen, and assessed their ability to activate a protective T-cell response in an animal model. First, we showed that specific mutations in the AAV6 capsid increase the transduction efficiency of these vectors in mouse bone marrow-derived dendritic cells in vitro for approximately 5-fold compared with the wild-type (WT) AAV6 vectors. Next, we evaluated the ability of the mutant AAV6 vectors to initiate specific T-cell clone proliferation in vivo. Our data indicate that the intramuscular administration of AAV6-S663V+T492V vectors expressing ovalbumin (OVA) led to a strong activation (approximately 9%) of specific T cells in peripheral blood compared with AAV6-WT treated animals (<1%). These OVA-specific T cells have a superior killing ability against mouse prostate cancer cell line RM1 stably expressing the OVA antigen when propagated in vitro. Finally, we evaluated the ability of capsid-optimized AAV6-S663V+T492V vectors to initiate a protective anticancer immune response in vivo. Our results document the suppression of subcutaneous tumor growth in animals immunized with AAV6 S663V+T492V vectors expressing prostatic acid phosphatase (PAP) for approximately 4 weeks in comparison with 1 week and 2 weeks for the negative controls, AAV6 EGFP, and AAV6-WT-PAP treated mice, respectively. These studies suggest that successful inhibition of tumor growth in an animal model would set the stage for potential clinical application of the capsid-optimized AAV6-S663V+T492V vectors. PMID- 26261895 TI - Is power-space a continuum? Distance effect during power judgments. AB - Despite the increasing evidence suggesting that power processing can activate vertical space schema, it still remains unclear whether this power-space is dichotomic or continuous. Here we tested the nature of the power-space by the distance effect, a continuous property of space cognition. In two experiments, participants were required to judge the power of one single word (Experiment 1) or compare the power of two words presented in pairs (Experiment 2). The power distance was indexed by the absolute difference of power ratings. Results demonstrated that reaction time decreased with the power distance, whereas accuracy increased with the power distance. The findings indicated that different levels of power were presented as different vertical heights, implying that there was a common mechanism underlying space and power cognition. PMID- 26261894 TI - Feasibility Study of a Novel Experimental Induction Protocol Combining B43-PAP (Anti-CD19) Immunotoxin With Standard Induction Chemotherapy in Children and Adolescents With Relapsed B-Lineage ALL: A Report From the Children's Oncology Group. AB - BACKGROUND: B43-pokeweed antiviral protein (B43-PAP) is a high-affinity anti-CD19 immunotoxin that is capable of causing apoptotic death in B-lineage leukemic cells with a drug-resistant phenotype. B43-PAP exhibited in vivo antileukemic activity in preclinical studies as well as on a single-agent phase I clinical trial. This pediatric phase I/II study evaluated the toxicity profile and efficacy of B43-PAP immunotoxin in combination with standard induction chemotherapy in children and adolescents with relapsed CD19-positive B-lineage acute lymphoblastic leukemia (B-ALL). Pharmacokinetic profile and immunogenicity of B43-PAP were assessed. EXPERIMENTAL DESIGN: B43-PAP in combination with standard 3 and 4-drug induction chemotherapy was administered on days 9-13 and 21 25 of a 28-day treatment course with vincristine, prednisone, L-asparaginase, daunomycin, and intrathecal methotrexate. Thirty patients with relapsed B-ALL were enrolled on study CCG-0957. RESULTS: Grade III/IV nonhematologic dose limiting toxicities were encountered in 4 patients evaluable for toxicity and included myalgias, motor dysfunction, pulmonary toxicity, and elevated liver transaminase. Dose-limiting toxicities occurred only with the 4-drug regimen. Fourteen patients achieved a complete remission at the end of induction among the 20 patients evaluable for response. CONCLUSIONS: B43-PAP in combination with standard induction chemotherapy can be safely administered and exhibits clinical antileukemic activity against relapsed B-ALL. PMID- 26261896 TI - The left visual field attentional advantage: No evidence of different speeds of processing across visual hemifields. AB - Temporal-order judgment (TOJ) and simultaneity judgment (SJ) tasks are used to study differences in speed of processing across sensory modalities, stimulus types, or experimental conditions. Matthews and Welch (2015) reported that observed performance in SJ and TOJ tasks is superior when visual stimuli are presented in the left visual field (LVF) compared to the right visual field (RVF), revealing an LVF advantage presumably reflecting attentional influences. Because observed performance reflects the interplay of perceptual and decisional processes involved in carrying out the tasks, analyses that separate out these influences are needed to determine the origin of the LVF advantage. We re analyzed the data of Matthews and Welch (2015) using a model of performance in SJ and TOJ tasks that separates out these influences. Parameter estimates capturing the operation of perceptual processes did not differ between hemifields by these analyses, whereas parameter estimates capturing the operation of decisional processes differed. In line with other evidence, perceptual processing also did not differ between SJ and TOJ tasks. Thus, the LVF advantage occurs with identical speeds of processing in both visual hemifields. If attention is responsible for the LVF advantage, it does not exert its influence via prior entry. PMID- 26261897 TI - An Engineered SS Bridge Blocks the Conformational Change Required for the Nuclease Activity of BfiI. AB - The type IIS restriction endonuclease BfiI is a homodimer, and each monomer is composed of the N-terminal catalytic and C-terminal DNA recognition domains connected by a 28-residue linker segment. In the crystal in the absence of cognate DNA, BfiI exists in a "closed" conformation, in which an interdomain linker occludes a putative DNA binding surface at the catalytic domain and sterically hinders access to the active site. Cognate DNA binding presumably triggers a conformational change from the inactive "closed" state to the catalytically competent "open" state. Here we show that the disulfide SS bridge engineered at the domain interface locks the enzyme in the "closed" state. In the "closed" SS-linked state, BfiI binds cognate DNA with the same affinity as the wild-type enzyme but does not cut it, indicating that cross-linking introduces a restraint on the conformational transition, which couples DNA recognition and cleavage. Disruption of the interdomain SS bridge by the reducing agent restores the DNA cleavage ability of BfiI. PMID- 26261898 TI - A hydrothermally stable Zn(ii)-based metal-organic framework: structural modulation and gas adsorption. AB - By the solvothermal reaction of a triangular ligand, 2,4,6-tris-(4 carboxyphenoxy)-1,3,5-triazine (H3tcpt) with Zn(NO3)2.6H2O in N,N' dimethylacetamide/acetonitrile/H2O (v/v/v = 1 : 1 : 1) mixed solvents, a two fold, interpenetrated, three-dimensional (3D), porous metal-organic framework, [Zn2(tcpt)OH].solvents (1.solvents), with a rare, paddlewheel secondary building unit (SBU), Zn2(COO)3, was synthesized and characterized. It was found that a single 3D structure of 1 forms when two-dimensional layers, which are constructed by tcpt(3-) bonding with the paddlewheel SBUs, are linked by -OH groups along the axial sites of the SBUs. Compared with the reported Zn(ii)-based partners with this ligand, synthesis conditions, particularly the solvents used, clearly played a key role in the formation of different SBUs, thereby resulting in distinct MOFs with the same ligand. In particular, 1 features good water and thermal stability and can withstand acidic aqueous solutions with pH values ranging from 5 to 12. In addition, 1 displays good adsorption ability towards H2 (2.21 wt% at 77 K and 1 atm) and can selectively adsorb CO2 from CH4 and N2, in spite of its relatively low void volume (36.8%), suggesting potential applications in gas storage and separation. PMID- 26261899 TI - Genetic data from algae sedimentary DNA reflect the influence of environment over geography. AB - Genetic investigations on eukaryotic plankton confirmed the existence of modern biogeographic patterns, but analyses of palaeoecological data exploring the temporal variability of these patterns have rarely been presented. Ancient sedimentary DNA proved suitable for investigations of past assemblage turnover in the course of environmental change, but genetic relatedness of the identified lineages has not yet been undertaken. Here, we investigate the relatedness of diatom lineages in Siberian lakes along environmental gradients (i.e. across treeline transects), over geographic distance and through time (i.e. the last 7000 years) using modern and ancient sedimentary DNA. Our results indicate that closely-related Staurosira lineages occur in similar environments and less related lineages in dissimilar environments, in our case different vegetation and co-varying climatic and limnic variables across treeline transects. Thus our study reveals that environmental conditions rather than geographic distance is reflected by diatom-relatedness patterns in space and time. We tentatively speculate that the detected relatedness pattern in Staurosira across the treeline could be a result of adaptation to diverse environmental conditions across the arctic boreal treeline, however, a geographically-driven divergence and subsequent repopulation of ecologically different habitats might also be a potential explanation for the observed pattern. PMID- 26261900 TI - Liquid phase solvent bonding of plastic microfluidic devices assisted by retention grooves. AB - We report a novel method for achieving consistent liquid phase solvent bonding of plastic microfluidic devices via the use of retention grooves at the bonding interface. The grooves are patterned during the regular microfabrication process, and can be placed at the periphery of a device, or surrounding microfluidic features with open ports, where they effectively mitigate solvent evaporation, and thus substantially reduce poor bond coverage. This method is broadly applicable to a variety of plastics and solvents, and produces devices with high bond quality (i.e., coverage, strength, and microfeature fidelity) that are suitable for studies in physics, chemistry, and cell biology at the microscale. PMID- 26261903 TI - Elucidating network mechanisms underlying hand actions (Commentary on Simone et al.). PMID- 26261902 TI - Biomarkers associated with severe hypoglycaemia and death in ACCORD. AB - AIMS AND HYPOTHESIS: In patients with Type 2 diabetes, intensive glycaemic control is associated with hypoglycaemia and possibly increased mortality. However, no blood biomarkers exist to predict these outcomes. Using participants from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, we hypothesized that insulin deficiency and islet autoantibodies in patients with clinically diagnosed Type 2 diabetes would be associated with severe hypoglycaemia and death. METHODS: A nested case-control study design was used. A case (n = 86) was a participant who died with at least one episode of severe hypoglycaemia, defined as hypoglycaemia requiring assistance, at any point during ACCORD follow-up. A control (n = 344) was a participant who did not die and did not have severe hypoglycaemia during follow-up. Each case was matched to four controls (glycaemic intervention arm, race, age and BMI). Baseline insulin deficiency (fasting C-peptide <= 0.15 nmol/l) and islet autoantibodies [glutamic acid decarboxylase (GAD), tyrosine phosphatase-related islet antigen 2 (IA2), insulin (IAA) and zinc transporter (ZnT8)] were measured. Conditional logistic regression with and without adjustment for age, BMI and diabetes duration was used. RESULTS: Death during ACCORD in those who experienced at least one episode of severe hypoglycaemia was associated with insulin deficiency [OR 4.8 (2.1, 11.1): P < 0.0001], GAD antibodies [OR 2.3 (1.1, 5.1): P = 0.04], the presence of IAA or baseline insulin use [OR 6.1 (3.5,10.7): P < 0.0001], which remained significant after adjusting for age, BMI, and diabetes duration. There was no significant association with IA2 or ZnT8 antibodies. CONCLUSIONS: In patients with Type 2 diabetes, C-peptide or GAD antibodies may serve as blood biomarkers predicting higher odds of subsequent severe hypoglycaemia and death. (Clinical Trial Registry No: NCT00000620, www.clinicaltrials.gov for original ACCORD study). PMID- 26261904 TI - Temporal orienting of attention: An fNIRS study on the illusion of "a watched pot never boils". AB - The present study used a single-task paradigm in which participants received guidance to focus more attention (waiting for someone) on the temporal intervals in the "waiting" condition and to stay relaxed in the control condition. The reported time was longer in the waiting condition than in the control condition. Functional near-infrared spectroscopy was used to measure simultaneously the activation levels of the dorsolateral prefrontal cortex (DLPFC) for each condition. Greater oxyhemoglobin (oxy-Hb) activation in the waiting condition was observed compared with the control condition, whilst deoxyhemoglobin data showed no difference between the two conditions. The gradual changes in oxy-Hb in the DLPFC in increments of 100 ms yielded further insights into the role of this region in the "watched pot never boils" phenomenon. PMID- 26261905 TI - Adapting cognitive behavioral therapy to meet the needs of Chinese clients: Opportunities and challenges. AB - With the growing influence of China (Chinese people/culture) on the world's politics, economy, and culture, the psychological wellbeing of Chinese people is becoming increasingly important for both researchers and practitioners. Despite this, the cultural responsiveness of many conventional psychotherapeutic models has often been brought into question. In contrast, cognitive behavioral therapy (CBT) is rapidly becoming one of the most popular approaches in the mental health service industry and has been successfully adapted into many different cultural contexts. The current article is a theoretical discussion of the opportunities and challenges that CBT faces with respect to how it might meet the cultural needs and preferences of Chinese clients. Suggestions for successful cultural adaptation are offered based on existing research and practices. It is concluded that many features of CBT appear to match well with the Chinese cultural perspective. However, despite this promising start further work is needed to focus specifically on its practical effectiveness for Chinese clients. PMID- 26261906 TI - The effects of incidental scents in the evaluation of environmental goods: The role of congruity. AB - We investigated whether pleasant ambient scents influence hypothetical and real money contributions toward environmental goods. We hypothesized that they would increase such contributions more when they were congruent with the target goods than when they were incongruent or when no scent was released. The results supported this congruity hypothesis. We offer a mental accessibility account: Pleasant scents that are congruent with a target good make positive information about that good more accessible and thus promote prosocial behavior. PMID- 26261907 TI - Factor structure and factorial invariance of the State-Trait Anxiety Inventory for Chinese children and adolescents. AB - As previous research utilizing Spielberger's State-Trait Anxiety Inventory (Form Y; STAI-Y) has mostly involved adults or clinical groups, there have been relatively few reports assessing adolescents. This study is the first using data for children and adolescents in mainland China, from a large-scale cross sectional survey in Beijing (Sample 1) and a longitudinal survey from the Wenchuan 512 earthquake (Sample 2), to clarify the factor structure and factorial invariance of the STAI-Y, Mandarin Chinese version. As a result, only in Sample 1 did a comparison of 11 confirmatory factor analysis models indicate the best goodness-of-fit indices shown by a two-factor structure for both state and trait anxiety, with both models reaching the selected cutoff criteria. These two optimal models were used in a subsequent simultaneous confirmatory factor analysis to test four conditions of factorial invariance, using eight participant groups divided on the basis of sex and school grade (fourth, fifth, sixth, and seventh to ninth). The two-factor structure state and trait anxiety models achieved the cutoff criteria for factorial invariance, with the exception of male fourth graders. Further, it was clearly shown that in comparison with the early stage of puberty, as puberty advanced the absence of state and trait anxiety gradually decreased, while scores for the presence of anxiety gradually increased. At the same time, in the case of Sample 2, which had experienced a traumatic event, as the goodness-of-fit indices for none of the 11 models reached the cutoff criteria, the factor scores showed arbitrariness and a lack of objectivity. The authors conclude that cognitive structure with regard to the STAI-Y may change with traumatic experience or the development of secondary sex characteristics at the onset of or in the stage of puberty. Also, computing the scores according to the STAI-Y manual is problematic. PMID- 26261901 TI - Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress. AB - Organic nitrates, such as nitroglycerin (GTN), isosorbide-5-mononitrate and isosorbide dinitrate, and pentaerithrityl tetranitrate (PETN), when given acutely, have potent vasodilator effects improving symptoms in patients with acute and chronic congestive heart failure, stable coronary artery disease, acute coronary syndromes, or arterial hypertension. The mechanisms underlying vasodilation include the release of *NO or a related compound in response to intracellular bioactivation (for GTN, the mitochondrial aldehyde dehydrogenase [ALDH-2]) and activation of the enzyme, soluble guanylyl cyclase. Increasing cyclic guanosine-3',-5'-monophosphate (cGMP) levels lead to an activation of the cGMP-dependent kinase I, thereby causing the relaxation of the vascular smooth muscle by decreasing intracellular calcium concentrations. The hemodynamic and anti-ischemic effects of organic nitrates are rapidly lost upon long-term (low dose) administration due to the rapid development of tolerance and endothelial dysfunction, which is in most cases linked to increased intracellular oxidative stress. Enzymatic sources of reactive oxygen species under nitrate therapy include mitochondria, NADPH oxidases, and an uncoupled *NO synthase. Acute high dose challenges with organic nitrates cause a similar loss of potency (tachyphylaxis), but with distinct pathomechanism. The differences among organic nitrates are highlighted regarding their potency to induce oxidative stress and subsequent tolerance and endothelial dysfunction. We also address pleiotropic effects of organic nitrates, for example, their capacity to stimulate antioxidant pathways like those demonstrated for PETN, all of which may prevent adverse effects in response to long-term therapy. Based on these considerations, we will discuss and present some preclinical data on how the nitrate of the future should be designed. PMID- 26261908 TI - The influence of pubertal timing and stressful life events on depression and delinquency among Chinese adolescents. AB - This study aimed to investigate the influences of pubertal timing and stressful life events on Chinese adolescents' depression and delinquency. Sex differences in these influences were also examined. A large sample with 4,228 participants aged 12-15 years (53% girls) was recruited in Beijing, China. Participants' pubertal development, stressful life events, depressive symptoms, and delinquency were measured using self-reported questionnaires. Both early maturing girls and boys displayed more delinquency than their same-sex on-time and late maturing peers. Early maturing girls displayed more depressive symptoms than on-time and late maturing girls, but boys in the three maturation groups showed similar levels of depressive symptoms. The interactive effects between early pubertal timing and stressful life events were significant in predicting depression and delinquency, particularly for girls. Early pubertal maturation is an important risk factor for Chinese adolescents' depression and delinquency. Stressful life events intensified the detrimental effects of early pubertal maturation on adolescents' depression and delinquency, particularly for girls. PMID- 26261910 TI - Corrigendum. AB - In connection with the article entitled "A randomized trial comparing the rate of hypoglycemia - assessed using continuous glucose monitoring - in 125 preschool children with type 1 diabetes treated with insulin glargine or NPH insulin (the PRESCHOOL study)" which appeared in [1], we wish to bring the following correction to your attention: In the acknowledgement section, we would like to add the name of the 2 investigators from Turkey to the supporting information file: Turkey: Ayla Guven, Nurgun Kandemir. PMID- 26261909 TI - Job insecurity and work-family conflict in teachers in Sweden: Examining their relations with longitudinal cross-lagged modeling. AB - Job insecurity and work-family conflict are increasingly prevalent in contemporary working life and numerous studies have documented their antecedents and negative consequences. The present study used longitudinal questionnaire data collected among teachers in Sweden to test the direction of the relation between job insecurity and work-family conflict using cross-lagged modeling. Multiple group comparisons were conducted to account for the skewed gender composition in the teachers' group. After controlling for baseline levels of job insecurity, work-family conflict, and four potential confounders (age, children under 12 living at home, university education, and relationship status), we found that the reciprocal relationship between job insecurity and work-family conflict over a 1 year time period fitted the data best for the men. For women, however, only the auto regression coefficients were significant. The results provide some empirical support for gender differences in the relation between job insecurity and work family conflict. Moreover, this study partially supports theoretical assumptions suggesting that job insecurity and work-family conflict influence each other. PMID- 26261911 TI - Corrigendum. AB - The authors wish to make the following corrections (shown in bold) to [1]:On page 116, "Introduction" section, second paragraph in second column, "1:00 hour" should be "1 AM". The sentence should read as:'Insulin therapy started in 1922 using regular insulin before each main meal and one injection in the night, usually at 1 AM'.On page 118, Table 1 should appear as follows. PMID- 26261912 TI - Gynecologic Cancer InterGroup (GCIG) Consensus Review for Clear Cell Carcinoma of the Ovary: Erratum. PMID- 26261914 TI - The Ipsilateral Adjacent Laminae: A Reliable Guide in Determining the Direction of Subaxial Cervical Pedicle Axis in the Sagittal Plane. AB - STUDY DESIGN: A retrospective radiographic analysis and applied anatomical study. OBJECTIVE: The aim of this study was to evaluate the relationships between the ipsilateral lamina/laminae and pedicle axis in the sagittal plane, and the feasibility of free hand pedicle screw placement in subaxial cervical spine without intraoperative fluoroscopic guidance. SUMMARY OF BACKGROUND DATA: The morphology of subaxial cervical spine pedicle has been studied extensively. However, to our knowledge, no study has specifically evaluated the relationships between the ipsilateral lamina/laminae and pedicle axis in the sagittal plane on computed tomography (CT) reconstruction images. METHODS: Axial CT images of 70 adult cases were obtained. Multi-directional pedicle axis reconstruction images of subaxial cervical spines were analyzed. Both the angle formed by the direction of ipsilateral lamina to the pedicle axis in the oblique sagittal plane (lamina pedicle angle, LPA) and the angle formed by the tangential line passing the ipsilateral adjacent outer laminae cortex to the pedicle axis in the oblique sagittal plane (tangential line pedicle angle, TPA) were recorded. On the basis of the radiographic data, a "T"-shaped guiding tool was designed, and the accuracy of free hand subaxial pedicle screw placement using the guiding tool was evaluated in 12 cadavers. RESULTS: A total of 350 vertebrae were analyzed. Averaged LPA ranged from 72.2 degrees at C3 to 84.2 degrees at C6, averaged TPA ranged from 89.8 degrees at C3 to 90.7 degrees at C6. The TPA showed a high level of consistency close to a right angle. A total of 115 inserted subaxial cervical pedicle screws on 12 cadavers were evaluated. The rate of screw insertion without pedicle wall penetration was 98%, and the rate of pedicle wall penetration of more than 2 mm in the sagittal plane was 0%. CONCLUSIONS: The TPA serves to be a reliable guide in determining the direction of subaxial cervical pedicle axis in the sagittal plane. Free hand placement of subaxial pedicle screw is feasible under the guidance of the newly designed guiding tool based on TPA. LEVEL OF EVIDENCE: 5. PMID- 26261913 TI - Impact of C4'-O-Alkyl Linker on in Vivo Pharmacokinetics of Near-Infrared Cyanine/Monoclonal Antibody Conjugates. AB - Near-infrared (NIR) fluorophores have several advantages over visible-light fluorophores, including superior tissue penetration and lower autofluorescence. We recently accessed a new class of readily synthesized NIR cyanines containing a novel C4'-O-alkyl linker, which provides both high chemical stability and excellent optical properties. In this study, we provide the first in vivo analysis of this new class of compounds, represented by the tetrasulfonate FNIR 774 (Frederick NIR 774). Monoclonal antibody (mAb) conjugates of FNIR-774 were compared to conjugates of the commercially available dye (IRDye800CW (IR800)), one of the most widely used NIR fluorophores for clinical translation. Both dyes were conjugated to panitumumab (pan) or cetuximab (cet) with ratios of 1:2 or 1:5. Conjugates of both dyes demonstrated similar quenching capacity, stability, and brightness in target cells in vitro. In contrast, in vivo imaging in mice showed different pharmacokinetics between pan-FNIR-774 (1:5) and pan-IR800 (1:5), or cet-FNIR-774 (1:5) and cet-IR800 (1:5). Particularly at the higher labeling density, mAb-FNIR-774 conjugates showed superior specific accumulation in tumors compared with mAb-IR800 conjugates. Thus, FNIR-774 conjugates showed superior in vivo pharmacokinetics compared with IR800 conjugates, independent of the mAb. These results suggest that FNIR-774 is a promising fluorescent probe for NIR optical imaging. PMID- 26261915 TI - Prediction of Curve Correction Using Alternate Level Pedicle Screw Placement in Patients With Adolescent Idiopathic Scoliosis (AIS) Lenke 1 and 2 Using Supine Side Bending (SB) and Fulcrum Bending (FB) Radiograph. AB - STUDY DESIGN: Prospective cohort study. OBJECTIVE: To compare side bending (SB) and fulcrum bending (FB) radiographs in patients with adolescent idiopathic scoliosis (AIS) and effect of magnitude and AR curves on curve correctability. SUMMARY OF BACKGROUND DATA: The prediction of correction using side bending flexibility (SBF) and fulcrum bending flexibility (FBF) in alternate level pedicle screw (PS) configuration and effect of curve magnitude and AR curves are not well understood. METHODS: 100 AIS Lenke 1 and 2 were recruited. Curve magnitude was stratified to G1 (41 degrees -60 degrees ), G2 (61 degrees -80 degrees ), G3 (>80 degrees ). The main thoracic (MT) curves were subclassified to AR curves [Miyanji F, Pawelek JB, Van Valin SE, et al. Is the lumbar modifier useful in surgical decision making? Defining two distinct Lenke 1A curve patterns. Spine 2008;33:2545-51]. Preoperatively SBF and FBF were determined whereas postoperative parameters were correction rate (CR), fulcrum bending correction index (FBCI), and side bending correction index (SBCI). Correlation test were carried out between SBF, FBF versus CR for the cohort. RESULTS: There were 38 (G1), 42 (G2), and 20 (G3) patients. 34% were AR curves. SBF for G1, G2, and G3 were 61.3 +/- 14.4, 59.2 +/- 16.2 and 43.1 +/- 13.1% (P = 0.000) whereas FBF for G1, G2, and G3 were 71.1 +/- 16.5, 58.3 +/- 18.1 and 52.7 +/- 17.1% (P = 0.000). The CR was G1 (74.5 +/- 11.5%), G2 (69.2 +/- 12.7%), and G3 (70.2 +/- 8.6%). FBCI was 1.11 +/- 0.3 (G1), 1.28 +/- 0.4 (G2) and 1.48 +/- 0.6 for G3. SBCI was 1.26 +/- 0.2 (G1), 1.50 +/- 0.5 (G2), and 1.72 +/- 0.4 for G3. There was strong correlation for SBF and FBF versus CR for G1 and G2. For G3, a very strong correlation was established between SBF (r = 0.846, r = 0.716) and FBF versus CR (r = 0.700, r = 0.540). AR curves demonstrated higher SBF and FBF. CONCLUSION: CR remains almost constant in G1, G2, and G3. SBCI and FBCI increase significantly in G1, G2, and G3. Correlation between SBF and FBF and CR was strong for G1, G2, and very strong for G3. AR curves showed better correctability with SB and FB films. PMID- 26261916 TI - Reoperation Rates for Symptomatic Nonunions in Anterior Cervical Fusions From a National Spine Registry. AB - STUDY DESIGN: A retrospective cohort study with chart review. OBJECTIVE: To determine the reoperation rates for symptomatic nonunions for 1-level, 2-level, and 3-level anterior cervical discectomies and fusions (ACDFs) from a national spine registry. SUMMARY OF BACKGROUND DATA: There is very little data reported in the literature on reoperation rates for symptomatic nonunions after ACDFs. The reported nonunion rates are primarily based on radiographical evidence, although some of these may be asymptomatic. Similarly, there may be symptomatic patients with nonunions who elect not to have a reoperation. We think, however, data from a national spine registry provide a realistic and unbiased assessment of routine cervical spine fusion care and represent a heterogeneous population with varied indications and surgical techniques and are best suited to determine reoperations for symptomatic nonunions. METHODS: Using data from a Spine Implant Registry developed at a large integrated health care system (Kaiser Permanente), patients with ACDFs between January 2009 and December 2012 with 2-year follow-up were identified. Patient characteristics, admitting diagnosis, and number of levels fused were extracted from the registry. Reoperations for symptomatic nonunions from the index spinal procedure were identified by chart review. RESULTS: A cohort of 1054 patients with more than 2 years of follow-up were found to have reoperations for nonunions of 0.2%, 2.9%, and 6.5% for 1-level, 2-level, and 3 level ACDFs, respectively. CONCLUSION: A large cohort of ACDF patients with more than 2 years of follow-up had reoperations for nonunion rates significantly lower than reported in the literature for radiographical nonunions. We think our data add to the literature an important parameter (reoperations for nonunion rates) and provide useful information for patients, spine surgeons, and health care payers. PMID- 26261917 TI - Validation and Reliability Analysis of the Spinal Deformity Study Group Classification for L5-S1 Lumbar Spondylolisthesis. AB - STUDY DESIGN: An intra- and interobserver reliability study. OBJECTIVE: To assess the intra- and interobserver reliability of the Spinal Deformity Study Group (SDSG) system for classifying adolescent and adult L5-S1 spondylolisthesis. SUMMARY OF BACKGROUND DATA: Reliability of the SDSG classification has only been previously validated in adolescent patients as performed by the SDSG study group investigators. METHODS: A total of 80 patients with L5-S1 spondylolisthesis were included in this study. Only dysplastic and isthmic spondylolisthesis were included in this study. Long-cassette standing lateral radiographs of the spine and pelvis were obtained. All 80 cases were classified according to the SDSG classification by four observers. After a 2-week interval, the same classification was independently repeated by each observer with the cases in a different randomly assigned order. The Fleiss' kappa coefficient was calculated to test the intra- and interobserver reliabilities of the SDSG classification. RESULTS: The present study included all six types of SDSG classification. Overall intra- and interobserver agreements were 86.6% (kappa: 0.830) and 73.3% (kappa: 0.648), respectively. The intra- and interobserver agreements and repeatability associated with slip grade were 89.7% (kappa: 0.824) and 87.7% (kappa: 0.721), respectively. Regarding sacropelvic and spinal balance, intra- and interobserver agreements and repeatability were 83.7% (kappa: 0.735) and 77.5% (kappa: 0.602) for low-grade slips, and 90.75% (kappa: 0.883) and 90.4% (kappa: 0.851) for high grade slips, respectively. CONCLUSION: Substantial intra- and interobserver reliability was found for the SDSG classification in L5-S1 lumbar spondylolisthesis. SDSG classification system is a simple and clear classification scheme incorporating spinopelvic parameters, which provides significant clinical utility. LEVEL OF EVIDENCE: 3. PMID- 26261918 TI - Predicting Short-term Morbidity in Patients Undergoing Posterior Spinal Fusion for Neuromuscular Scoliosis. AB - STUDY DESIGN: A retrospective cohort study. OBJECTIVE: The aim of this study was to determine the incidence and risk factors for short-term morbidity following posterior spinal fusion (PSF) for neuromuscular scoliosis (NMS). SUMMARY OF BACKGROUND DATA: NMS is a challenging spinal deformity for which PSF is often recommended. There is a lack of information on risk factors for short-term adverse outcomes after PSF for NMS. METHODS: Patients who underwent PSF for NMS during 2012 and 2013 were identified from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) Pediatric database. Patient characteristics were tested for association with adverse events, infectious complications, extended length of stay (LOS), and readmission using multivariate regression. RESULTS: Of the 940 NMS patients identified, 133 (14.1%) had an adverse event and 99 (10.5%) had a severe adverse event. American Society of Anesthesiologists (ASA) classification >=3 was found to be the only independent risk factor for any adverse event (relative risk [RR] 2.2, P = 0.012) and severe adverse events (RR 2.5, P = 0.008). Infectious complications were associated with body mass index (BMI)-for-age >=95th percentile (RR 2.8, P = 0.005), ASA classification >=3 (RR 5.9, P = 0.003), and instrumentation to the pelvis (RR 1.8, P = 0.039).A total of 254 patients (27%) spent longer than a week in the hospital postoperatively, and ASA classification >=3 (RR 2.3, P < 0.001), preoperative seizure disorder (RR 1.4, P = 0.002), previous cardiac surgery (RR 1.6, P = 0.004), operative time >=470 minutes (RR 1.8, P < 0.001), and >=13 levels instrumented (RR 1.9, P = 0.001) were associated with extended LOS.Seventy six patients (8.1%) were readmitted, and BMI-for-age >=95th percentile (RR 1.8, P = 0.033) was the only risk factor found for readmission. CONCLUSION: The identified factors associated with poor short-term outcomes after PSF for NMS can be used as benchmark data, be useful for optimizing patient care, and can inform future studies in these patients. LEVEL OF EVIDENCE: 3. PMID- 26261919 TI - CT-Based Anatomical Evaluation of Pre-Vertebral Structures With Respect to Vertebral Body Using a Clock-Face Analogy. AB - STUDY DESIGN: Retrospective Chart and CT Scan Review. OBJECTIVE: To define the relationship of the pre-vertebral structures for each level to assist in easier intraoperative visualization. SUMMARY OF BACKGROUND DATA: Vascular and visceral injuries from pedicle screws are well-known. This study will define the relationship of the pre-vertebral structures for each level to assist in avoiding potential complications. METHODS: Pre- and post-operative CT scans were reviewed to define the pre-vertebral structures in relation to a clock-face. On reformatted axial slices, a clock-face was superimposed so that the left transverse process (TP) represented 8 o'clock and the right TP represented 4 o'clock. The positions of the TP on the clock-face did not change with rotation of the vertebra. RESULTS: 108 patients had pre-operative CT scans. 78 had post operative CT scans. Median age was 15 years, median Cobb angle was 50 degrees , fused were 12, with 21 fixation points. 6324 axial CT slices were reformatted and analyzed. The trachea was located at 12 o'clock at T1, 1 o'clock at T2-T4, and between 12 and 1 o'clock at T5. The esophagus starts as a midline structure at 12 o'clock from T1-T2, moves to 11 o'clock from T3-T6, and further to 10 o'clock from T7-T9. The aorta starts at 10 o'clock at T5-T6, moves left at T7-T8 to 9 o'clock, and returns to 10 o'clock from T9-T11. It appears at 11'clock at T12, and at 12 o'clock from L1-L4. In about a third of cases, it is at 1 o'clock from L1 to L4, where it bifurcates. CONCLUSIONS: This CT-based anatomical study provides a simple reference frame to help surgeons visualize the vital structures at each level. This three-dimensional visualization is facilitated by fixing the position of TP on the clock-face. Knowledge of this anatomical relationship can help avoid direct injury, and is easier to recall intra-operatively. LEVEL OF EVIDENCE: 3. PMID- 26261920 TI - Intraoperative Cardiopulmonary Arrest in Children Undergoing Spinal Deformity Correction: Causes and Associated Factors. AB - STUDY DESIGN: Retrospective review. OBJECTIVE: To report the incidence of and risk factors for intraoperative cardiopulmonary arrest (ICA) in children undergoing spinal deformity surgery. SUMMARY OF BACKGROUND DATA: Spinal deformities in children are associated with comorbidities that can pose substantial risks during surgery. METHODS: We reviewed records of patients who underwent surgery at two pediatric tertiary-care hospitals from 2004 through 2014. Fisher exact test and the Student t test were used to compare ICA and non ICA groups by patient diagnosis, estimated blood loss, number of vertebral levels fused, and proportion of blood volume lost (significance, P < 0.05). We classified proximate causes of ICA based on hemoglobin, metabolic panel/electrolyte imbalance, electrocardiogram/echocardiography, and vital signs. RESULTS: ICA occurred in 11 of 2524 (0.4%) patients. Patients with neuromuscular disorders had a 3-fold higher risk of ICA compared with those without neuromuscular disorders. At the time of ICA, hemoglobin levels were 5 g/dL or less in four patients, potassium was higher than 5.5 mEq/L in six patients, and ionized calcium was less than or equal to 1 mmol/L in two patients. There were significant differences between the ICA and non-ICA groups in mean number of vertebral levels fused (15 vs. 12), patient weight (34 vs. 49 kg), estimated blood loss (2623 vs. 959 mL), and proportion of blood volume lost (1.03 vs. 0.33) (all P < 0.01). Suspected causes of ICA were cardiovascular causes (eight patients) and anaphylaxis, primary rhythm disturbance, and respiratory/airway cause (one patient each). The incidence of ICA for patients with idiopathic scoliosis was 0.13%. Ten of the 11 patients were successfully resuscitated, and one patient died. CONCLUSION: ICA occurs in approximately 0.4% of children undergoing spinal fusion surgery. Patients with neuromuscular disorders are at greater risk of ICA than those without these disorders. LEVEL OF EVIDENCE: 3. PMID- 26261921 TI - Arabidopsis COPPER MODIFIED RESISTANCE1/PATRONUS1 is essential for growth adaptation to stress and required for mitotic onset control. AB - The mitotic checkpoint (MC) guards faithful sister chromatid segregation by monitoring the attachment of spindle microtubules to the kinetochores. When chromosome attachment errors are detected, MC delays the metaphase-to-anaphase transition through the inhibition of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase. In contrast to yeast and mammals, our knowledge on the proteins involved in MC in plants is scarce. Transient synchronization of root tips as well as promoter-reporter gene fusions were performed to analyze temporal and spatial expression of COPPER MODIFIED RESISTANCE1/PATRONUS1 (CMR1/PANS1) in developing Arabidopsis thaliana seedlings. Functional analysis of the gene was carried out, including CYCB1;2 stability in CMR1/PANS1 knockout and overexpressor background as well as metaphase-anaphase chromosome status. CMR1/PANS1 is transcriptionally active during M phase. Its deficiency provokes premature cell cycle exit and in consequence a rapid consumption of the number of meristematic cells in particular under stress conditions that are known to affect spindle microtubules. Root growth impairment is correlated with a failure to delay the onset of anaphase, resulting in anaphase bridges and chromosome missegregation. CMR1/PANS1 overexpression stabilizes the mitotic CYCB1;2 protein. Likely, CMR1/PANS1 coordinates mitotic cell cycle progression by acting as an APC/C inhibitor and plays a key role in growth adaptation to stress. PMID- 26261922 TI - [Will physicians continue to do research in the future?]. PMID- 26261923 TI - [Asymptomatic carotid artery stenosis--is screening useful?]. AB - Stenoses of the carotid artery are associated with an increased stroke risk. Duplex ultrasound is the method of choice for screening for carotid artery stenosis. Unselected screening for carotid stenosis in unselected persons is not efficient and cannot be recommended. Screening by vascular ultrasound, however, is indicated in patients with neurologic symptoms from cerebral territories supplied by the anterior or mid cerebral artery, and in asymptomatic patients with carotid bruits, atherosclerotic disease in other vascular territories, after contralateral carotid artery revascularization, and after radiation therapy of the neck. PMID- 26261924 TI - [Hypoparathyroidism]. AB - Hypoparathyroidism and quality of life: Even in adequately substituted patients, hypoparathyroidism (HPT) is associated with impaired quality of life. It has been hypothesized that there is a correlation between reduced quality of life and lack of parathyroid hormone (PTH) in the central nervous system. Positive effects on quality of life have been reported when treating HPT with PTH. Hypoparathyroidism and comorbidities: Comorbidities associated with HPT include an increased risk of nephrolithiasis/nephrocalcinosis and neuro-psychiatric disease. Additionally, cardiovascular risk profile and an increased susceptibility for infections have been reported. Mortality rates seem not to be increased in HPT. Hypoparathyroidism and new therapeutic strategies: Recombinant PTH has not been approved for the treatment of HPT in Europe yet. However, in early 2015, the FDA approved PTH (1-84). Daily subcutaneous delivery of PTH (1-84) and PTH (1-34) (Teriparatide) has emerged as a promising therapeutic tool. However, its use should be restricted to patients insufficiently controlled with the standard treatment consisting of active vitamin d and calcium. PMID- 26261925 TI - [Chronic ulcers--consequences]. PMID- 26261926 TI - [Current standards in the treatment of gastric cancer]. AB - Endoscopic resection is established in the treatment of early gastric cancer. More advanced gastric cancer requires gastrectomy and D2 lymphadenectomy. Perioperative chemotherapy improves overall survival in locally advanced gastric cancer representing a standard of care. Locally advanced adenocarcinomas of the esophago-gastric junction can alternatively be treated with concurrent radiochemotherapy. In metastatic disease, systemic chemotherapy improves survival, quality of life and symptom control. Trastuzumab plus chemotherapy should be used together with first-line chemotherapy in HER2 positive gastric cancer patients. Second- and third-line therapy is now well established. The anti VEGFR2 antibody Ramucirumab improves survival in second line treatment both as a monotherapy and in combination with paclitaxel and represents a novel treatment option. PMID- 26261927 TI - [Q fever]. AB - The article summarizes some important recently identified findings about the Coxiella burnetii disease, Q fever. Beside new diagnostic parameters for follow up issues, the importance of a timely identification of chronic Q fever and the peculiarities of the post Q fever fatigue syndrome are depicted. PMID- 26261928 TI - [Implementation of therapeutic hypothermia into clinical practice]. AB - Implementation of mild therapeutic hypothermia after cardiac arrest into clinical practice is a continuing process. Although ILCOR recommendation was given in 2003, only 24% of the German hospitals reported the use of hypothermia in this setting in 2005. Growing evidence and most importantly the implementation of hypothermia into the guidelines led to a significant increase of acceptance of this therapeutic option leading to a user rate of 69% in 2009. Encouraged by the new guidelines from 2010 86% of German hospitals finally reported to use hypothermia after cardiac arrest routinely in 2012, a decade after publication of the mile stone studies. The phenomenon of a delayed implementation of hypothermia into clinical practice can be seen throughout the world as many surveys from different countries at different time points have shown. When hypothermia is used, hospitals go with the guidelines quite strictly with respect to indication, duration of treatment and target temperature. This strengthens the importance of guidelines in the process to implement new therapeutic options. However, although a recent study still promotes a strict target temperature management it questions the need for a markedly reduced target temperature of 33 degrees C. It remains to be elucidated how this study will affect the daily routine in the hospitals and most interestingly how this study will change the coming guidelines in 2015. PMID- 26261929 TI - [Prophylaxis of thromboembolism in atrial fibrillation: new oral anticoagulants and left atrial appendage closure]. AB - Thrombo-embolic prophylaxis is a key element within the therapy of atrial fibrillation/atrial flutter. Besides new oral anticoagulants the concept of left atrial appendage occlusion has approved to be a good alternative option, especially in patients with increased risk of bleeding. PMID- 26261930 TI - [Chronic kidney disease--update 2015]. PMID- 26261931 TI - [Treatment of pulmonal hypertension]. AB - While the clinical classification of diseases with pulmonary hypertension (PH) has remained fairly stable in recent years, the treatment options have improved significantly. In addition to the General measures (vaccinations, physical training) new recommendations for supportive therapy (administration of diuretics, iron supplementation and oral anticoagulant) exist currently. Some new substances (mostly in the indication pulmonary arterial hypertension) have been admitted to the targeted drug treatment in recent years. For the first time, exist a approved drug therapy for the non-operable and residual chronic thromboembolic pulmonary hypertension. PMID- 26261932 TI - [Ultrasound examination in rheumatoid arthritis]. AB - Musculoskeletal ultrasound in the clinical routine praxis increases the hit rate for the diagnosis of inflammatory joint diseases. Power Doppler ultrasound is helpful in the detection of subclinical synovitis in the small finger joints in patients with rheumatoid arthritis; subclinical synovitis can lead to severe joint destruction. Rigorous clinical remission criteria result in lower synovitis detected by power Doppler ultrasound. PMID- 26261933 TI - [New oral anticoagulants and endoscopy--what do you have to consider?]. AB - Anti-coagulated patients often undergo endoscopic procedures and non-vitamin-K antagonist oral anticoagulants (NOAC) are increasingly prescribed. Consequently, a comprehensive knowledge about the adequate peri-interventional handling of these substances is required. A standardized approach needs to be planned for elective and emergency situations. As a result of their pharmacokinetics, the peri-endoscopic management of NOAC is relatively easy - an heparin "bridging"/"switching" is usually not required. In case of a severe NOAC bleeding endoscopic treatment must be considered at an early stage. PMID- 26261934 TI - [39-year-old man with 15 years lasting pain in both hands]. PMID- 26261936 TI - Shedding of Water Drops from a Surface under Icing Conditions. AB - A sessile water drop exposed to an air flow will shed if the adhesion is overcome by the external aerodynamic forces on the drop. In this study, shedding of water drops were investigated under icing conditions, on surfaces with different wettabilities, from hydrophilic to superhydrophobic. A wind tunnel was used for experiments in a temperature range between -8 and 24.5 degrees C. Results indicate that the temperature has a major influence on the incipient motion of drop shedding. The critical air velocity (U(c)) at which a drop first starts to shed generally increases under icing conditions, indicating an increase in the adhesion force. The contact angle hysteresis (CAH) and the drop base length (L(b)) are found to be the controlling factors for adhesion. A correlation was also developed to deduce the drag coefficient, C(D) for the drop. It was found that C(D) can decrease under icing conditions. In general, a lower C(D) and higher adhesion together lead to a higher critical air velocity. However, there are systems such as water on Teflon for which the critical air velocity remains practically unaffected by temperature because of similar adhesion and C(D) values, at all temperatures tested. PMID- 26261935 TI - [Fecal microbiota transfer (FMT) in a patient with refractory irritable bowel syndrome]. AB - Irritable bowel syndrome is a disorder of the gastrointestinal tract with unknown etiology. Recent clinical data support a link between changes in fecal microbiota with decreased biodiversity and the development of irritable bowel syndrome. Whether these changes of the microbiota are caused by the disease or whether they develop during the course of the disease remains unclear. Several studies demonstrated that fecal microbiota transfer (FMT) successfully attenuates Clostridium difficile infection by restoring the disturbed bacterial flora of the gut and case reports suggest that FMT may relief symptoms in patients with irritable bowel syndrome (IBS). Here we report a 47-year-old male patient with longstanding refractory diarrhea predominant IBS, who was successfully treated with a single FMT. The beneficial effect on the patient's symptoms was associated with changes of the stool microbiome. Post-FMT the recipient's microbiome resembled the donor's microbiome. PMID- 26261937 TI - High-Resolution Satellite-Derived PM2.5 from Optimal Estimation and Geographically Weighted Regression over North America. AB - We used a geographically weighted regression (GWR) statistical model to represent bias of fine particulate matter concentrations (PM2.5) derived from a 1 km optimal estimate (OE) aerosol optical depth (AOD) satellite retrieval that used AOD-to-PM2.5 relationships from a chemical transport model (CTM) for 2004-2008 over North America. This hybrid approach combined the geophysical understanding and global applicability intrinsic to the CTM relationships with the knowledge provided by observational constraints. Adjusting the OE PM2.5 estimates according to the GWR-predicted bias yielded significant improvement compared with unadjusted long-term mean values (R(2) = 0.82 versus R(2) = 0.62), even when a large fraction (70%) of sites were withheld for cross-validation (R(2) = 0.78) and developed seasonal skill (R(2) = 0.62-0.89). The effect of individual GWR predictors on OE PM2.5 estimates additionally provided insight into the sources of uncertainty for global satellite-derived PM2.5 estimates. These predictor driven effects imply that local variability in surface elevation and urban emissions are important sources of uncertainty in geophysical calculations of the AOD-to-PM2.5 relationship used in satellite-derived PM2.5 estimates over North America, and potentially worldwide. PMID- 26261939 TI - Momentum-Dependent Lifetime Broadening of Electron Energy Loss Spectra: A Self Consistent Coupled-Plasmon Model. AB - The complex dielectric function and associated energy loss spectrum of a condensed matter system is a fundamental material parameter that determines both the optical and electronic scattering behavior of the medium. The common representation of the electron energy loss function (ELF) is interpreted as the susceptibility of a system to a single- or bulk-electron (plasmon) excitation at a given energy and momentum and is commonly derived as a summation of noninteracting free-electron resonances with forms constrained by adherence to some externally determined optical standard. This work introduces a new causally constrained momentum-dependent broadening theory, permitting a more physical representation of optical and electronic resonances that agrees more closely with both optical attenuation and electron scattering data. We demonstrate how the momentum dependence of excitation resonances may be constrained uniquely by utilizing a coupled-plasmon model, in which high-energy excitations are able to relax into lower-energy excitations within the medium. This enables a robust and fully self-consistent theory with no free or fitted parameters that reveals additional physical insight not present in previous work. The new developments are applied to the scattering behavior of solid molybdenum and aluminum. We find that plasmon and single-electron lifetimes are significantly affected by the presence of alternate excitation channels and show for molybdenum that agreement with high-precision electron inelastic mean free path data is dramatically improved for energies above 20 eV. PMID- 26261940 TI - Time-Dependent, Optically Controlled Dielectric Function. AB - We suggest optical modulation of the dielectric function of a molecular monolayer adsorbed on a metal surface as a potential means of controlling plasmon resonance phenomena. The dielectric function is altered using a laser pulse of moderate intensity and linear polarization to align the constituent molecules. After the pulse, the monolayer returns to its initial state. Time-dependent, optically controlled dielectric function is illustrated by molecular dynamics calculations. PMID- 26261941 TI - Temperature- and Component-Dependent Degradation of Perovskite Photovoltaic Materials under Concentrated Sunlight. AB - We report on accelerated degradation testing of MAPbX3 films (X = I or Br) by exposure to concentrated sunlight of 100 suns and show that the evolution of light absorption and the corresponding structural modifications are dependent on the type of halide ion and the exposure temperature. One hour of such exposure provides a photon dose equivalent to that of one sun exposure for 100 hours. The degradation in absorption of MAPbI3 films after exposure to 100 suns for 60 min at elevated sample temperature (~45-55 degrees C), due to decomposition of the hybrid perovskite material, is documented. No degradation was observed after exposure to the same sunlight concentration but at a lower sample temperature (~25 degrees C). No photobleaching or decomposition of MAPbBr3 films was observed after exposure to similar stress conditions (light intensity, dose, and temperatures). Our results indicate that the degradation is highly dependent on the hybrid perovskite composition and can be light- and thermally enhanced. PMID- 26261942 TI - Nanopore-Based Sensors for Ligand-Receptor Lead Optimization. AB - Developing a low-cost and high-efficacy method to optimize prescreened or designed drug candidates will facilitate drug discovery and biomedical research in general. Current methods of drug screening usually involve tedious sample preparation and costly biological/chemical assays. Here, through all-atom molecular dynamics simulations, we propose a new drug optimization method, based on the nanopore force spectroscopy, to electrically detect the binding strength between a drug molecule and a target protein. Simulation results demonstrate that the drug-protein complex can be electrophoretically driven into a nanopore, which is followed by the rupture of the complex at a critical biasing voltage. The latter determines the binding strength of the tested drug molecule. It is expected that the application of this single-molecule technology could help to accelerate the drug discovery, particularly for processes of the narrow screening and further lead optimization. PMID- 26261943 TI - Loss of Memory in H + CH4 -> H2 + CH3 State-to-State Reactive Scattering. AB - State-to-state reaction probabilities for the H + CH4-> H2 + CH3 reaction are calculated by accurate full-dimensional quantum dynamics calculations employing the multilayer multiconfigurational time-dependent Hartree approach and the quantum transition-state concept. Reactions starting from different vibrational and rotational states of the methane reactant are investigated for vanishing total angular momentum. The vibrational state distributions of the products are found to be essentially independent of the initial rovibrational state of the reactants. The reaction products only show vibrational excitation in the methyl umbrella mode. No excitation in H2 vibration or another CH3 vibration is observed. Analyzing the results, the observed loss of vibrational memory can be explained by a transition-state-based view of the reaction process. PMID- 26261944 TI - Direct Observation of Ground-State Product Formation in a 1,3-Cyclohexadiene Ring Opening Reaction. AB - Ultrafast photoelectron imaging using a 90 nm vacuum-UV probe pulse is applied to the ring-opening reaction of 1,3-cyclohexadiene (CHD) in the gas phase, and formation of 1,3,5-hexatriene (HT) and CHD in their electronic ground states is observed in real time. The analysis of the transient photoelectron kinetic energy spectra reveals the branching ratio into HT and CHD as 3:7 upon 270 nm photoexcitation. The ratio is in reasonable agreement with the experimental values reported for the liquid phase and theoretical values for the gas phase, resolving the discrepancy. PMID- 26261945 TI - Correction to "Fast Solid-State Li Ion Conducting Garnet-Type Structure Metal Oxides for Energy Storage". PMID- 26261946 TI - Direct Signature of Light-Induced Conical Intersections in Diatomics. AB - Nonadiabatic effects are ubiquitous in physics, chemistry, and biology. They are strongly amplified by conical intersections (CIs), which are degeneracies between electronic states of triatomic or larger molecules. A few years ago it was revealed that CIs in molecular systems can be formed by laser light, even in diatomics. Because of the prevailing strong nonadiabatic couplings, the existence of such laser-induced conical intersections (LICIs) may considerably change the dynamical behavior of molecular systems. By analyzing the photodissociation process of the D2+ molecule carefully, we found a robust effect in the angular distribution of the photofragments that serves as a direct signature of the LICI, providing undoubted evidence of its existence. PMID- 26261947 TI - DNA Electronic Circular Dichroism on the Inter-Base Pair Scale: An Experimental Theoretical Case Study of the AT Homo-Oligonucleotide. AB - A successful elucidation of the near-ultraviolet electronic circular dichroism spectrum of a short double-stranded DNA is reported. Time-dependent density functional theory methods are shown to accurately predict spectra and assign bands on the microscopic base-pair scale, a finding that opens the field for using circular dichroism spectroscopy as a sensitive nanoscale probe of DNA to reveal its complex interactions with the environment. PMID- 26261948 TI - Intermolecular Vibrational Modes Speed Up Singlet Fission in Perylenediimide Crystals. AB - We report numerical simulations based on a non-Markovian density matrix propagation scheme of singlet fission (SF) in molecular crystals. Ab initio electronic structure calculations were used to parametrize the exciton and phonon Hamiltonian as well as the interactions between the exciton and the intramolecular and intermolecular vibrational modes. We demonstrate that the interactions of the exciton with intermolecular vibrational modes are highly sensitive to the stacking geometry of the crystal and can, in certain cases, significantly accelerate SF. This result may help in understanding the fast SF experimentally observed in a broad range of molecular crystals and offers a new direction for the engineering of efficient SF sensitizers. PMID- 26261949 TI - Ab Initio Quantum Approaches to the IR Spectroscopy of Water and Hydrates. AB - This Perspective highlights progress in ab initio quantum approaches to IR spectroscopy of water and hydrates. Here, "ab initio" refers to many-body potentials and dipole moment surfaces for flexible water and hydrates. Specifically, these are mathematical representations of two-body and three-body interactions based on permutationally invariant fitting of tens of thousands of ab initio electronic energies, a spectroscopically accurate one-body monomer potential, and four- and higher-body interactions described by the long-range interactions incorporated into, for example, the TTM3-F family of potentials. There are currently two such potentials of this type, denoted WHBB and MB-pol, which are being used in expanding applications. Here, the focus is on infrared spectroscopy, using the WHBB potential and dipole moment surface, with an embedded, local monomer quantum method to obtain vibrational energies and dipole transition moments. Comparisons are also made with the popular q-TIP4P/F potential. Brief mention is made of an application to small HCl-H2O clusters. PMID- 26261950 TI - Super-Resolution Single-Molecule Localization Microscopy: Tricks of the Trade. AB - Application of single-molecule fluorescence detection has led to the development of light microscopy techniques that make it possible to study fluorescent samples at spatial resolutions significantly improved upon the diffraction limit of light. The biological and materials science applications of these "super resolution" microscopy methods are vast, causing current demand for them to be high. However, implementation, execution, and interpretation of these techniques, particularly involving biological samples, require a broad interdisciplinary skillset, not often found in a single laboratory. Those already used to interdisciplinary work as well as navigating communication and collaboration between more pure forms of physics, chemistry, and biology are well-positioned to spearhead such efforts. In this Perspective, we describe various aspects of single-molecule super-resolution imaging, discussing, in particular, the role that physical chemistry has so far played in its development and establishment. We also highlight a selection of some of the remarkable recent research achievements in this vibrant field. PMID- 26261951 TI - Production of and Dissociative Electron Attachment to the Simplest Criegee Intermediate in an Afterglow. AB - The simplest Criegee intermediate, CH2OO, has been produced in a flowing afterglow using a novel technique. CH2I is produced by dissociative electron attachment to CH2I2, leading to the established reaction CH2I + O2 -> CH2OO + I. The presence of CH2OO is established by observation of dissociative electron attachment to yield O(-) using the variable electron and neutral density attachment mass spectrometry (VENDAMS) technique. The measurements establish the electron attachment rate coefficient of thermal electrons at 300 K to CH2OO as 1.2 +/- 0.3 * 10(-8) cm(3) s(-1). Thermal electron attachment is solely dissociative and is not a promising route to producing stable CH2OO(-). The results open the possibility of measuring ion-molecule chemistry involving Criegee intermediates, as well as the reactivity of other unstable radicals produced in an analogous manner. PMID- 26261953 TI - Looking beneath the Diffraction Limit and Inside of the Bulk. PMID- 26261954 TI - Assembly of Ferrocene Molecules on Metal Surfaces Revisited. AB - Metallocene (MCp2) wires have recently attracted considerable interest in relation to molecular spintronics due to predictions concerning their half metallic nature. This exciting prospect is however hampered by the little and often-contradictory knowledge we have concerning the metallocene self-assembly and interaction with a metal. Here, we elucidate these aspects by focusing on the adsorption of ferrocene on Cu(111) and Cu(100). Combining low-temperature scanning tunneling microscopy and density functional theory calculations, we demonstrate that the two-dimensional molecular arrangement consists of vertical- and horizontal-lying molecules. The noncovalent T-shaped interactions between Cp rings of vertical and horizontal molecules are essential for the stability of the physisorbed molecular layer. These results provide a fresh insight into ferrocene adsorption on surfaces and may serve as an archetypal reference for future work with this important variety of organometallic molecules. PMID- 26261952 TI - Protein Adsorption Alters Hydrophobic Surfaces Used for Suspension Culture of Pluripotent Stem Cells. AB - This Letter examines the physical and chemical changes that occur at the interface of methyl-terminated alkanethiol self-assembled monolayers (SAMs) after exposure to cell culture media used to derive embryoid bodies (EBs) from pluripotent stem cells. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy analysis of the SAMs indicates that protein components within the EB cell culture medium preferentially adsorb at the hydrophobic interface. In addition, we examined the adsorption process using surface plasmon resonance and atomic force microscopy. These studies identify the formation of a porous, mat-like adsorbed protein film with an approximate thickness of 2.5 nm. Captive bubble contact angle analysis reveals a shift toward superhydrophilic wetting behavior at the cell culture interface due to adsorption of these proteins. These results show how EBs are able to remain in suspension when derived on hydrophobic materials, which carries implications for the rational design of suspension culture interfaces for lineage specific stem-cell differentiation. PMID- 26261955 TI - Raman Spectroscopy of Organic-Inorganic Halide Perovskites. AB - Micro-Raman spectroscopy provides laterally resolved microstructural information for a broad range of materials. In this Letter, we apply this technique to tri iodide (CH3NH3PbI3), tribromide (CH3NH3PbBr3), and mixed iodide-bromide (CH3NH3PbI3-xBrx) organic-inorganic halide perovskite thin films and discuss necessary conditions to obtain reliable data. We explain how to measure Raman spectra of pristine CH3NH3PbI3 layers and discuss the distinct Raman bands that develop during moisture-induced degradation. We also prove unambiguously that the final degradation products contain pure PbI2. Moreover, we describe CH3NH3PbI3 xBrx Raman spectra and discuss how the perovskite crystallographic symmetries affect the Raman band intensities and spectral shapes. On the basis of the dependence of the Raman shift on the iodide-to-bromide ratio, we show that Raman spectroscopy is a fast and nondestructive method for the evaluation of the relative iodide-to-bromide ratio. PMID- 26261956 TI - Dipolar Nanodomains in Protein Hydration Shells. AB - The network of hydrogen bonds characteristic of bulk water is significantly disturbed at the protein-water interface, where local fields induce mutually frustrated dipolar domains with potentially novel structure and dynamics. Here the dipolar susceptibility of hydration shells of lysozyme is studied by molecular dynamics simulations in a broad range of temperatures, 140-300 K. The real part of the susceptibility passes through a broad maximum as a function of temperature. The maximum shifts to higher temperatures with increasing frequency of the dielectric experiment. This phenomenology is consistent with that reported for bulk relaxor ferroelectrics, where it is related to the formation of dipolar nanodomains. Nanodomains in the hydration shell extend 12-15 A from the protein surface into the bulk. Their dynamics are significantly slower than the dynamics of bulk water. The domains dynamically freeze into a ferroelectric glass below 160 K, at which point the Arrhenius plot of the dipolar relaxation time becomes significantly steeper. PMID- 26261957 TI - Sonoporation at Small and Large Length Scales: Effect of Cavitation Bubble Collapse on Membranes. AB - Ultrasound has emerged as a promising means to effect controlled delivery of therapeutic agents through cell membranes. One possible mechanism that explains the enhanced permeability of lipid bilayers is the fast contraction of cavitation bubbles produced on the membrane surface, thereby generating large impulses, which, in turn, enhance the permeability of the bilayer to small molecules. In the present contribution, we investigate the collapse of bubbles of different diameters, using atomistic and coarse-grained molecular dynamics simulations to calculate the force exerted on the membrane. The total impulse can be computed rigorously in numerical simulations, revealing a superlinear dependence of the impulse on the radius of the bubble. The collapse affects the structure of a nearby immobilized membrane, and leads to partial membrane invagination and increased water permeation. The results of the present study are envisioned to help optimize the use of ultrasound, notably for the delivery of drugs. PMID- 26261958 TI - Dynamics of N2 Dissociation upon Inner-Valence Ionization by Wavelength-Selected XUV Pulses. AB - Ionization of nitrogen by extreme ultraviolet (XUV) light from the Sun has recently been recognized as an important driver of chemical reactions in the atmosphere of Titan. XUV photons with energies of 24 eV and above convert inert nitrogen molecules into reactive neutral and ionic fragments that initiate chemical reactions. Understanding the XUV-induced fragmentation poses significant challenges to modern theory owing to its ultrafast time scales, complex electronic rearrangements, and strong dependence on the XUV photon energy. Here, we apply femtosecond time-resolved photoelectron and photoion spectroscopy to study dissociative ionization of nitrogen, the most abundant molecule in Titan's atmosphere, at selected XUV photon energies using a table-top XUV time compensating monochromator. We probe the resulting dynamics using a time-delayed infrared (IR) ionization pulse. Coupled with ab initio calculations, the results allow us to assign the major dissociation channels resulting from production of an inner-valence hole, with important implications for models of Titan's XUV driven atmospheric chemistry. PMID- 26261959 TI - Attosecond Hole Migration in Benzene Molecules Surviving Nuclear Motion. AB - Hole migration is a fascinating process driven by electron correlation, in which purely electronic dynamics occur on a very short time scale in complex ionized molecules, prior to the onset of nuclear motion. However, it is expected that due to coupling to the nuclear dynamics, these oscillations will be rapidly damped and smeared out, which makes experimental observation of the hole migration process rather difficult. In this Letter, we demonstrate that the instantaneous ionization of benzene molecules initiates an ultrafast hole migration characterized by a periodic breathing of the hole density between the carbon ring and surrounding hydrogen atoms on a subfemtosecond time scale. We show that these oscillations survive the dephasing introduced by the nuclear motion for a long enough time to allow their observation. We argue that this offers an ideal benchmark for studying the influence of hole migration on molecular reactivity. PMID- 26261960 TI - Improving the Long-Term Stability of Perovskite Solar Cells with a Porous Al2O3 Buffer Layer. AB - Hybrid perovskites represent a new paradigm for photovoltaics, which have the potential to overcome the performance limits of current technologies and achieve low cost and high versatility. However, an efficiency drop is often observed within the first few hundred hours of device operation, which could become an important issue. Here, we demonstrate that the electrode's metal migrating through the hole transporting material (HTM) layer and eventually contacting the perovskite is in part responsible for this early device degradation. We show that depositing the HTM within an insulating mesoporous "buffer layer" comprised of Al2O3 nanoparticles prevents the metal electrode migration while allowing for precise control of the HTM thickness. This enables an improvement in the solar cell fill factor and prevents degradation of the device after 350 h of operation. PMID- 26261961 TI - Time-Resolved Raman Spectroscopy of Polaron Pair Formation in Poly(3 hexylthiophene) Aggregates. AB - The ultrafast formation of bound charge pairs, or polaron pairs (PPs), in mixed order aggregates of poly(3-hexylthiophene) was investigated using femtosecond stimulated Raman spectroscopy (FSRS). Spectral dynamics in the carbon-carbon stretching region reveal a significant photoinduced depletion in steady-state features associated with lamellar-stacked, ordered polymer regions upon 500 nm photoexcitation; this is followed by the appearance of red-shifted features attributable to PPs that is delayed by a few hundred femtoseconds. PP features decay with concomitant recovery of the steady-state Raman depletion over a few picoseconds. The vibrational spectrum of the PP obtained exhibits a modest red shift (<15 cm(-1)) and lower Raman activity relative to steady-state features in the C?C stretching region but similar features in other regions. In total, this work demonstrates the potential of time-resolved Raman as a morphologically selective and structurally sensitive probe for tracking ultrafast charge separation and recombination dynamics within polymer regions of conjugated materials. PMID- 26261962 TI - Relationship between Dynamic Planarization Processes and Exciton Delocalization in Cyclic Oligothiophenes. AB - In cyclic molecular structures, while the effect of conformational disorder on exciton delocalization is well understood, the impact of dynamic planarization processes remains unclear due to a lack of detailed investigation on the associated exciton dynamics. Thus, we have investigated the exciton delocalization of pi-conjugated linear and cyclic oligothiophenes in the course of dynamic planarization processes by time-resolved fluorescence spectra measurements and theoretical calculations. Especially, through a comparative analysis of linear and cyclic oligothiophenes, we found that the evolution of 0-0 and 0-1 vibronic bands is strongly related to the conformations of cyclic molecular systems, reflecting the extent of exciton delocalization. Collectively, we believe that our findings are applicable to various pi-conjugated organic materials and will provide new insights into the relationship between exciton delocalization and cyclic molecular conformation. PMID- 26261963 TI - Surface Contributions to Mn(2+) Spin Dynamics in Colloidal Doped Quantum Dots. AB - Colloidal impurity-doped quantum dots (QDs) are attractive model systems for testing the fundamental spin properties of semiconductor nanostructures relevant to future spin-based information processing technologies. Although static spin properties of this class of materials have been studied extensively in recent years, their spin dynamics remain largely unexplored. Here we use pulsed electron paramagnetic resonance (pEPR) spectroscopy to probe the spin relaxation dynamics of colloidal Mn(2+)-doped ZnO, ZnSe, and CdSe quantum dots in the limit of one Mn(2+) per QD. pEPR spectroscopy is particularly powerful for identifying the specific nuclei that accelerate electron spin relaxation in these QDs. We show that the spin-relaxation dynamics of these colloidal QDs are strongly influenced by dipolar coupling with proton nuclear spins outside the QDs and especially those directly at the QD surfaces. Using this information, we demonstrate that spin-relaxation times can be elongated significantly via ligand (or surface) deuteration or shell growth, providing two tools for chemical adjustment of spin dynamics in these nanomaterials. These findings advance our understanding of the spin properties of solution-grown semiconductor nanostructures relevant to spin based information technologies. PMID- 26261964 TI - Time-Resolved In Situ Spectroscopy During Formation of the GaP/Si(100) Heterointerface. AB - Though III-V/Si(100) heterointerfaces are essential for future epitaxial high performance devices, their atomic structure is an open historical question. Benchmarking of transient optical in situ spectroscopy during chemical vapor deposition to chemical analysis by X-ray photoelectron spectroscopy enables us to distinguish between formation of surfaces and of the heterointerface. A terrace related optical anisotropy signal evolves during pulsed GaP nucleation on single domain Si(100) surfaces. This dielectric anisotropy agrees well with the one calculated for buried GaP/Si(100) interfaces from differently thick GaP epilayers. X-ray photoelectron spectroscopy reveals a chemically shifted contribution of the P and Si emission lines, which quantitatively corresponds to one monolayer and establishes simultaneously with the nucleation-related optical in situ signal. We attribute that contribution to the existence of Si-P bonds at the buried heterointerface. During further pulsing and annealing in phosphorus ambient, dielectric anisotropies known from atomically well-ordered GaP(100) surfaces superimpose the nucleation-related optical in situ spectra. PMID- 26261965 TI - Pump-Probe Noise Spectroscopy of Molecular Junctions. AB - The slow response of electronic components in junctions limits the direct applicability of pump-probe type spectroscopy in assessing the intramolecular dynamics. Recently the possibility of getting information on a sub-picosecond time scale from dc current measurements was proposed. We revisit the idea of picosecond resolution by pump-probe spectroscopy from dc measurements and show that any intramolecular dynamics not directly related to charge transfer in the current direction is missed by current measurements. We propose a pump-probe dc shot noise spectroscopy as a suitable alternative. Numerical examples of time dependent and average responses of junctions are presented for generic models. PMID- 26261966 TI - Role of Spin-Triplet Polycyclic Aromatic Hydrocarbons in Soot Surface Growth. AB - Using density functional theory, a possible pathway of soot surface growth is studied in the low-temperature, postflame region in which spin-triplet polycyclic aromatic hydrocarbon (PAH) molecules with a small singlet-triplet energy gap react with unsaturated aliphatics such as acetylene via the carbon-addition hydrogen-migration (CAHM) reaction. Results show that a PAH-core-aliphatic-shell structure is formed and the mass growth rate of this triplet soot surface growth reaction is one order of magnitude larger than that of the surface hydrogen abstraction-carbon-addition (HACA) reaction at temperatures below 1500 K. PMID- 26261967 TI - Spontaneous Defect Annihilation in CH3NH3PbI3 Thin Films at Room Temperature Revealed by Time-Resolved Photoluminescence Spectroscopy. AB - We utilized time-resolved photoluminescence (PL) spectroscopy to investigate the photocarrier recombination dynamics in CH3NH3PbI3 thin films as a function of the time elapsed from the film's fabrication. We found that the PL lifetime gradually increased and began to level out once the age of the film reached ~30 h. Even under weak excitation, the PL dynamics depended on the excitation intensity in the fresh sample, while the mature sample displayed no excitation-intensity dependence associated with the PL dynamics. We submit that this can be explained by the fact that a significant number of defects are initially formed in CH3NH3PbI3 thin films fabricated by the sequential method and are spontaneously reduced by room-temperature annealing. Our results provide important insights for reducing the nonradiative recombination centers, which improves the power conversion efficiency of perovskite solar cells. PMID- 26261968 TI - Role of Strain and Conductivity in Oxygen Electrocatalysis on LaCoO3 Thin Films. AB - The slow kinetics of the oxygen reduction and evolution reactions (ORR, OER) hinder energy conversion and storage in alkaline fuel cells and electrolyzers employing abundant transition metal oxide catalysts. Systematic studies linking material properties to catalytic activity are lacking, in part due to the heterogeneous nature of powder-based electrodes. We demonstrate, for the first time, that epitaxial strain can tune the activity of oxygen electrocatalysis in alkaline solutions, focusing on the model chemistry of LaCoO3, where moderate tensile strain can further induce changes in the electronic structure leading to increased activity. The resultant decrease in charge transfer resistance to the electrolyte reduces the overpotential in the ORR more notably than the OER and suggests a different dependence of the respective rate-limiting steps on electron transfer. This provides new insight into the reaction mechanism applicable to a range of perovskite chemistries, key to the rational design of highly active catalysts. PMID- 26261969 TI - Fabrication of Planar Heterojunction Perovskite Solar Cells by Controlled Low Pressure Vapor Annealing. AB - A new method for achieving high efficiency planar CH3NH3I3-xClx perovskite photovoltaics, based on a low pressure, reduced temperature vapor annealing is demonstrated. Heterojunction devices based on this hybrid halide perovskite exhibit a top PCE of 16.8%, reduced J-V hysteresis, and highly repeatable performance without need for a mesoporous or nanocrystalline metal oxide layer. Our findings demonstrate that large hysteresis is not an inherent feature of planar heterojunctions, and that efficient charge extraction can be achieved with uniform halide perovskite materials with desired composition. X-ray diffraction, valence band spectroscopy, and transient absorption measurements of these thin films reveal that structural modifications induced by chlorine clearly dominate over chemical and electronic doping effects, without affecting the Fermi level or photocarrier lifetime in the material. PMID- 26261970 TI - Charge Transfer Absorption and Emission at ZnO/Organic Interfaces. AB - We investigate hybrid charge transfer states (HCTS) at the planar interface between alpha-NPD and ZnO by spectrally resolved electroluminescence (EL) and external quantum efficiency (EQE) measurements. Radiative decay of HCTSs is proven by distinct emission peaks in the EL spectra of such bilayer devices in the NIR at energies well below the bulk alpha-NPD or ZnO emission. The EQE spectra display low energy contributions clearly red-shifted with respect to the alpha-NPD photocurrent and partially overlapping with the EL emission. Tuning of the energy gap between the ZnO conduction band and alpha-NPD HOMO level (Eint) was achieved by modifying the ZnO surface with self-assembled monolayers based on phosphonic acids. We find a linear dependence of the peak position of the NIR EL on Eint, which unambiguously attributes the origin of this emission to radiative recombination between an electron on the ZnO and a hole on alpha-NPD. In accordance with this interpretation, we find a strictly linear relation between the open-circuit voltage and the energy of the charge state for such hybrid organic-inorganic interfaces. PMID- 26261971 TI - Reversible Photoswitching of the Interfacial Nonlinear Optical Response. AB - Incorporating photochromic molecules into organic/inorganic hybrid materials may lead to photoresponsive systems. In such systems, the second-order nonlinear properties can be controlled via external stimulation with light at an appropriate wavelength. By creating photochromic molecular switches containing self-assembled monolayers on Si(111), we can demonstrate efficient reversible switching, which is accompanied by a pronounced modulation of the nonlinear optical (NLO) response of the system. The concept of utilizing functionalized photoswitchable Si surfaces could be a way for the generation of two-dimensional NLO switching materials, which are promising for applications in photonic and optoelectronic devices. PMID- 26261972 TI - Transport of Polarons in Graphene Nanoribbons. AB - The field-induced dynamics of polarons in armchair graphene nanoribbons (GNRs) is theoretically investigated in the framework of a two-dimensional tight-binding model with lattice relaxation. Our findings show that the semiconductor behavior, fundamental to polaron transport to take place, depends upon of a suitable balance between the GNR width and the electron-phonon (e-ph) coupling strength. In a similar way, we found that the parameter space for which the polaron is dynamically stable is limited to an even narrower region of the GNR width and the e-ph coupling strength. Interestingly, the interplay between the external electric field and the e-ph coupling plays the role to define a phase transition from subsonic to supersonic velocities for polarons in GNRs. PMID- 26261973 TI - Copper Induces a Core Plasmon in Intermetallic Au(144,145)-xCux(SR)60 Nanoclusters. AB - The electronic structure and optical absorption spectra of intermetallic thiol stabilized gold-copper clusters, having 144-145 metal atoms and 60 thiols, were studied by ab initio computations. The widely known icosahedral-based cluster model from the work of Lopez-Acevedo et al. (2009) was used, and clusters doped with one to 30 copper atoms were considered. When doped inside the metal core, copper induces dramatic changes in the optical spectrum as compared to the previously studied all-gold Au144(SR)60. An intense broad absorption peak develops in the range 535-587 nm depending on the amount of doping and doping sites. This result agrees very well with recent experiments by the Dass group for Au144-xCux(SR)60 (x <= 23). The analysis of the peaks shows a collective plasmon like dipole oscillation of the electron density in the metal core. Internal charge transfer from copper to gold and an almost perfect alignment of the upper edges of Cu(3d) and Au(5d) bands are observed in the metal core, contributing to the plasmon-like absorption. The calculations also predict energetically preferable doping of the ligand layer by copper, but such clusters are nonplasmonic. PMID- 26261974 TI - Stepwise Oxidation of Aqueous Dicarboxylic Acids by Gas-Phase OH Radicals. AB - A leading source of uncertainty in predicting the climate and health effects of secondary organic aerosol (SOA) is how its composition changes over their atmospheric lifetimes. Because dicarboxylic acid (DCA) homologues are widespread in SOA, their distribution provides an ideal probe of both aerosol age and the oxidative power of the atmosphere along its trajectory. Here we report, for the first time, on the oxidation of DCA(aq) by .OH(g) at the air-water interface. We found that exposure of aqueous HOOC-Rn-COOH (Rn = C2H4, C3H6, C4H8, C5H10, and C6H12) microjets to ~10 ns .OH(g) pulses from the 266 nm laser photolysis of O3(g)/O2(g)/H2O(g) mixtures yields the corresponding (n-1) species O?C(H)-Rn-1 COO(-)/HOOC-Rn-1-COO(-), in addition to an array of closed-shell HOOC-Rn(-H)(OOH) COO(-), HOOC-Rn(-2H)(?O)-COO(-), HOOC-Rn(-H)(OH)-COO(-), and radical HOOC-Rn( H)(OO.)-COO(-) species. Oxalic and malonic acids, which are shown to be significantly less hydrophobic and reactive than their higher homologues, will predictably accumulate in SOA, in accordance with field observations. PMID- 26261975 TI - Air-Stable and Solution-Processable Perovskite Photodetectors for Solar-Blind UV and Visible Light. AB - Stable perovskite CH3NH3PbI3-xClx for a photodetector was prepared through spin coating of a fluorous polymer as a light protection layer. The best responsivity of photodetector was 14.5 A/W to white light and 7.85 A/W for solar-blind UV light (lambda = 254 nm). The response time was in the submicrosecond range. The fluorous polymer coating increases the lifetime of the devices to almost 100 days. PMID- 26261976 TI - The Theoretical Estimation of the Bioluminescent Efficiency of the Firefly via a Nonadiabatic Molecular Dynamics Simulation. AB - The firefly is famous for its high bioluminescent efficiency, which has attracted both scientific and public attention. The chemical origin of firefly bioluminescence is the thermolysis of the firefly dioxetanone anion (FDO(-)). Although considerable theoretical research has been conducted, and several mechanisms were proposed to elucidate the high efficiency of the chemi- and bioluminescence of FDO(-), there is a lack of direct experimental and theoretical evidence. For the first time, we performed a nonadiabatic molecular dynamics simulation on the chemiluminescent decomposition of FDO(-) under the framework of the trajectory surface hopping (TSH) method and theoretically estimated the chemiluminescent quantum yield. The TSH simulation reproduced the gradually reversible charge-transfer initiated luminescence mechanism proposed in our previous study. More importantly, the current study, for the first time, predicted the bioluminescence efficiency of the firefly from a theoretical viewpoint, and the theoretical prediction efficiency is in good agreement with experimental measurements. PMID- 26261977 TI - Complementary Molecular Dynamics and X-ray Reflectivity Study of an Imidazolium Based Ionic Liquid at a Neutral Sapphire Interface. AB - Understanding the molecular-level behavior of ionic liquids (ILs) at IL-solid interfaces is of fundamental importance with respect to their application in, for example, electrochemical systems and electronic devices. Using a model system, consisting of an imidazolium-based IL ([C2Mim][NTf2]) in contact with a sapphire substrate, we have approached this problem using a complementary combination of high-resolution X-ray reflectivity measurements and atomistic molecular dynamics (MD) simulations. Our strategy enabled us to compare experimental and theoretically calculated reflectivities in a direct manner, thereby critically assessing the applicability of several force-field variants. On the other hand, using the best-matching MD description, we are able to describe the nature of the model IL-solid interface in appreciable detail. More specifically, we find that characteristic interactions between the surface hydroxyl groups and donor and acceptor sites on the IL constituents have a dominant role in inducing a multidimensional layering profile of the cations and anions. PMID- 26261978 TI - NIR to VUV: Seven-Photon Upconversion Emissions from Gd(3+) Ions in Fluoride Nanocrystals. AB - Here we show that a near-infrared (NIR) diode laser is capable of generating vacuum ultraviolet (VUV) emissions in fluoride nanocrystals through photon upconversion (UC) processes. By using Yb(3+) and Tm(3+) as sensitizers, we successfully obtained the VUV photons with the energy exceeding 6 eV in YF3: Yb, Tm, and Gd nanocrystals. The seven photon UC fluorescence from the (6)GJ -> (8)S7/2 transitions of Gd(3+) ions and the possible VUV UC mechanism were reported along with the calculation of the branching ratio under different pumping power excitation. Practically, it offers a promising solution for VUV light generation without cryogens and expensive instrumentations. Fundamentally, the extremely high-order UC processes will intrigue great interest in exploring unusual high-energy radiative transitions in rare earth ions. PMID- 26261979 TI - X-ray Birefringence Imaging of Materials with Anisotropic Molecular Dynamics. AB - The X-ray birefringence imaging (XBI) technique, reported very recently, is a sensitive tool for spatially resolved mapping of the local orientational properties of anisotropic materials. In this paper, we report the first XBI measurements on materials that undergo anisotropic molecular dynamics. Using incident linearly polarized X-rays with energy close to the Br K-edge, the X-ray birefringence is dictated by the orientational properties of the C-Br bonds in the material. We focus on two materials (urea inclusion compounds containing 1,8 dibromooctane and 1,10-dibromodecane guest molecules) for which the reorientational dynamics of the brominated guest molecules (and hence the reorientational dynamics of the C-Br bonds) are already well characterized by other experimental techniques. The XBI results demonstrate clearly that, for the anisotropic molecular dynamics in these materials, the effective X-ray optic axis for the X-ray birefringence phenomenon is the time-averaged resultant of the orientational distribution of the C-Br bonds. PMID- 26261981 TI - Ultrafast Charge-Transfer Dynamics at the Boron Subphthalocyanine Chloride/C60 Heterojunction: Comparison between Experiment and Theory. AB - Photoinduced charge-transfer (CT) processes play a key role in many systems, particularly those relevant to organic photovoltaics and photosynthesis. Advancing the understanding of CT processes calls for comparing their rates measured via state-of-the-art time-resolved interface-specific spectroscopic techniques with theoretical predictions based on first-principles molecular models. We measure charge-transfer rates across a boron subphthalocyanine chloride (SubPc)/C60 heterojunction, commonly used in organic photovoltaics, via heterodyne-detected time-resolved second-harmonic generation. We compare these results to theoretical predictions based on a Fermi's golden rule approach, with input parameters obtained using first-principles calculations for two different equilibrium geometries of a molecular donor-acceptor in a dielectric continuum model. The calculated rates (~2 ps(-1)) overestimate the measured rates (~0.1 ps( 1)), which is consistent with the expectation that the calculated rates represent an upper bound over the experimental ones. The comparison provides valuable understanding of how the structure of the electron donor-acceptor interface affects the CT kinetics in organic photovoltaic systems. PMID- 26261982 TI - PINGU: PredIction of eNzyme catalytic residues usinG seqUence information. AB - Identification of catalytic residues can help unveil interesting attributes of enzyme function for various therapeutic and industrial applications. Based on their biochemical roles, the number of catalytic residues and sequence lengths of enzymes vary. This article describes a prediction approach (PINGU) for such a scenario. It uses models trained using physicochemical properties and evolutionary information of 650 non-redundant enzymes (2136 catalytic residues) in a support vector machines architecture. Independent testing on 200 non redundant enzymes (683 catalytic residues) in predefined prediction settings, i.e., with non-catalytic per catalytic residue ranging from 1 to 30, suggested that the prediction approach was highly sensitive and specific, i.e., 80% or above, over the incremental challenges. To learn more about the discriminatory power of PINGU in real scenarios, where the prediction challenge is variable and susceptible to high false positives, the best model from independent testing was used on 60 diverse enzymes. Results suggested that PINGU was able to identify most catalytic residues and non-catalytic residues properly with 80% or above accuracy, sensitivity and specificity. The effect of false positives on precision was addressed in this study by application of predicted ligand-binding residue information as a post-processing filter. An overall improvement of 20% in F measure and 0.138 in Correlation Coefficient with 16% enhanced precision could be achieved. On account of its encouraging performance, PINGU is hoped to have eventual applications in boosting enzyme engineering and novel drug discovery. PMID- 26261984 TI - Trophic Dynamics of Filter Feeding Bivalves in the Yangtze Estuarine Intertidal Marsh: Stable Isotope and Fatty Acid Analyses. AB - Benthic bivalves are important links between primary production and consumers, and are essential intermediates in the flow of energy through estuarine systems. However, information on the diet of filter feeding bivalves in estuarine ecosystems is uncertain, as estuarine waters contain particulate matter from a range of sources and as bivalves are opportunistic feeders. We surveyed bivalves at different distances from the creek mouth at the Yangtze estuarine marsh in winter and summer, and analyzed trophic dynamics using stable isotope (SI) and fatty acid (FA) techniques. Different bivalve species had different spatial distributions in the estuary. Glauconome chinensis mainly occurred in marshes near the creek mouth, while Sinonovacula constricta preferred the creek. Differences were found in the diets of different species. S. constricta consumed more diatoms and bacteria than G. chinensis, while G. chinensis assimilated more macrophyte material. FA markers showed that plants contributed the most (38.86 +/ 4.25%) to particular organic matter (POM) in summer, while diatoms contributed the most (12.68 +/- 1.17%) during winter. Diatoms made the largest contribution to the diet of S. constricta in both summer (24.73 +/- 0.44%) and winter (25.51 +/- 0.59%), and plants contributed no more than 4%. This inconsistency indicates seasonal changes in food availability and the active feeding habits of the bivalve. Similar FA profiles for S. constricta indicated that the bivalve had a similar diet composition at different sites, while different delta13C results suggested the diet was derived from different carbon sources (C4 plant Spartina alterniflora and C3 plant Phragmites australis and Scirpus mariqueter) at different sites. Species-specific and temporal and/or spatial variability in bivalve feeding may affect their ecological functions in intertidal marshes, which should be considered in the study of food webs and material flows in estuarine ecosystems. PMID- 26261983 TI - A Multi-Breed Genome-Wide Association Analysis for Canine Hypothyroidism Identifies a Shared Major Risk Locus on CFA12. AB - Hypothyroidism is a complex clinical condition found in both humans and dogs, thought to be caused by a combination of genetic and environmental factors. In this study we present a multi-breed analysis of predisposing genetic risk factors for hypothyroidism in dogs using three high-risk breeds--the Gordon Setter, Hovawart and the Rhodesian Ridgeback. Using a genome-wide association approach and meta-analysis, we identified a major hypothyroidism risk locus shared by these breeds on chromosome 12 (p = 2.1x10(-11)). Further characterisation of the candidate region revealed a shared ~167 kb risk haplotype (4,915,018-5,081,823 bp), tagged by two SNPs in almost complete linkage disequilibrium. This breed shared risk haplotype includes three genes (LHFPL5, SRPK1 and SLC26A8) and does not extend to the dog leukocyte antigen (DLA) class II gene cluster located in the vicinity. These three genes have not been identified as candidate genes for hypothyroid disease previously, but have functions that could potentially contribute to the development of the disease. Our results implicate the potential involvement of novel genes and pathways for the development of canine hypothyroidism, raising new possibilities for screening, breeding programmes and treatments in dogs. This study may also contribute to our understanding of the genetic etiology of human hypothyroid disease, which is one of the most common endocrine disorders in humans. PMID- 26261985 TI - A Methodological Framework to Estimate the Site Fidelity of Tagged Animals Using Passive Acoustic Telemetry. AB - The rapid expansion of the use of passive acoustic telemetry technologies has facilitated unprecedented opportunities for studying the behavior of marine organisms in their natural environment. This technological advance would greatly benefit from the parallel development of dedicated methodologies accounting for the variety of timescales involved in the remote detection of tagged animals related to instrumental, environmental and behavioral events. In this paper we propose a methodological framework for estimating the site fidelity ("residence times") of acoustic tagged animals at different timescales, based on the survival analysis of continuous residence times recorded at multiple receivers. Our approach is validated through modeling and applied on two distinct datasets obtained from a small coastal pelagic species (bigeye scad, Selar crumenophthalmus) and a large, offshore pelagic species (yellowfin tuna, Thunnus albacares), which show very distinct spatial scales of behavior. The methodological framework proposed herein allows estimating the most appropriate temporal scale for processing passive acoustic telemetry data depending on the scientific question of interest. Our method provides residence times free of the bias inherent to environmental and instrumental noise that can be used to study the small scale behavior of acoustic tagged animals. At larger timescales, it can effectively identify residence times that encompass the diel behavioral excursions of fish out of the acoustic detection range. This study provides a systematic framework for the analysis of passive acoustic telemetry data that can be employed for the comparative study of different species and study sites. The same methodology can be used each time discrete records of animal detections of any nature are employed for estimating the site fidelity of an animal at different timescales. PMID- 26261986 TI - Functional Assessment of Residues in the Amino- and Carboxyl-Termini of Crustacean Hyperglycemic Hormone (CHH) in the Mud Crab Scylla olivacea Using Point-Mutated Peptides. AB - To assess functional importance of the residues in the amino- and carboxyl termini of crustacean hyperglycemic hormone in the mud crab Scylla olivacea (Sco CHH), both wild-type and point-mutated CHH peptides were produced with an amidated C-terminal end. Spectral analyses of circular dichroism, chromatographic retention time, and mass spectrometric analysis of the recombinant peptides indicate that they were close in conformation to native CHH and were produced with the intended substitutions. The recombinant peptides were subsequently used for an in vivo hyperglycemic assay. Two mutants (R13A and I69A rSco-CHH) completely lacked hyperglycemic activity, with temporal profiles similar to that of vehicle control. Temporal profiles of hyperglycemic responses elicited by 4 mutants (I2A, F3A, D12A, and D60A Sco-CHH) were different from that elicited by wild-type Sco-CHH; I2A was unique in that it exhibited significantly higher hyperglycemic activity, whereas the remaining 3 mutants showed lower activity. Four mutants (D4A, Q51A, E54A, and V72A rSco-CHH) elicited hyperglycemic responses with temporal profiles similar to those evoked by wild-type Sco-CHH. In contrast, the glycine-extended version of V72A rSco-CHH (V72A rSco-CHH-Gly) completely lost hyperglycemic activity. By comparing our study with previous ones of ion-transport peptide (ITP) and molt-inhibiting hormone (MIH) using deleted or point-mutated mutants, detail discussion is made regarding functionally important residues that are shared by both CHH and ITP (members of Group I of the CHH family), and those that discriminate CHH from ITP, and Group-I from Group-II peptides. Conclusions summarized in the present study provide insights into understanding of how functional diversification occurred within a peptide family of multifunctional members. PMID- 26261987 TI - A Randomized Controlled Trial of a Brief Intervention for Delayed Psychological Effects in Snakebite Victims. AB - BACKGROUND: Snakebite results in delayed psychological morbidity and negative psycho-social impact. However, psychological support is rarely provided to victims. AIM: To assess the effectiveness of a brief intervention which can be provided by non-specialist doctors aimed at reducing psychological morbidity following snakebite envenoming. METHOD: In a single blind, randomized controlled trial, snakebite victims with systemic envenoming [n = 225, 168 males, mean age 42.1 (SD 12.4) years] were randomized into three arms. One arm received no intervention (n = 68, Group A), the second received psychological first aid and psychoeducation (dispelling prevalent cultural beliefs related to snakebite which promote development of a sick role) at discharge from hospital (n = 65, Group B), while the third received psychological first aid and psychoeducation at discharge and a second intervention one month later based on cognitive behavioural principles (n = 69, Group C). All patients were assessed six months after hospital discharge for the presence of psychological symptoms and level of functioning using standardized tools. RESULTS: At six months, there was a decreasing trend in the proportion of patients who were positive for psychiatric symptoms of depression and anxiety from Group A through Group B to Group C (Chi square test for trend = 7.901, p = 0.005). This was mainly due to a decreasing trend for symptoms of anxiety (chi-square for trend = 11.256, p = 0.001). There was also decreasing trend in the overall prevalence of disability from Group A through Group B to Group C (chi square for trend = 7.551, p = 0.006), predominantly in relation to disability in family life (p = 0.006) and social life (p = 0.005). However, there was no difference in the proportion of patients diagnosed with depression between the three groups (chi square for trend = 0.391, p = 0.532), and the intervention also had no effect on post-traumatic stress disorder. CONCLUSIONS: A brief psychological intervention, which included psychological first aid and psychoeducation plus cognitive behavioural therapy that can be provided by non-specialist doctors appeared to reduce psychiatric symptoms and disability after snakebite envenoming, but not depression or post traumatic stress disorder. TRIAL REGISTRATION: Sri Lanka Clinical Trials Registry: SLCTR/2011/003. PMID- 26261988 TI - HLA Allele E*01:01 Is Associated with a Reduced Risk of EBV-Related Classical Hodgkin Lymphoma Independently of HLA-A*01/*02. AB - BACKGROUND: An inefficient immune response against Epstein-Barr virus (EBV) infection is related to the pathogenesis of a subgroup of classical Hodgkin lymphomas (cHL). Some EBV immune-evasion mechanisms target HLA presentation, including the non-classical HLA-E molecule. HLA-E can be recognized by T cells via the TCR, and it also regulates natural killer (NK) cell signaling through the inhibitory CD94/NKG2A receptor. Some evidences indicate that EBV-infected B-cells promote the proliferation of NK subsets bearing CD94/NKG2A, suggesting a relevant function of these cells in EBV control. Variations in CD94/NKG2A-HLA-E interactions could affect NK cell-mediated immunity and, consequently, play a role in EBV-driven transformation and lymphomagenesis. The two most common HLA-E alleles, E*01:01 and E*01:03, differ by a single amino acid change that modifies the molecule function. We hypothesized that the functional differences in these variants might participate in the pathogenicity of EBV. AIM: We studied two series of cHL patients, both with EBV-positive and-negative cases, and a cohort of unrelated controls, to assess the impact of HLA-E variants on EBV-related cHL susceptibility. RESULTS: We found that the genotypes with at least one copy of E*01:01 (i.e., E*01:01 homozygous and heterozygous) were underrepresented among cHL patients from both series compared to controls (72.6% and 71.6% vs 83%, p = 0.001). After stratification by EBV status, we found low rates of E*01:01 carriers mainly among EBV-positive cases (67.6%). These reduced frequencies are seen independently of other factors such as age, gender, HLA-A*01 and HLA-A*02, HLA alleles positively and negatively associated with the disease (adjusted OR = 0.4, p = 0.001). Furthermore, alleles from both HLA loci exert a cumulative effect on EBV-associated cHL susceptibility. CONCLUSIONS: These results indicate that E*01:01 is a novel protective genetic factor in EBV-associated cHL and support a role for HLA-E recognition on the control of EBV infection and lymphomagenesis. PMID- 26261990 TI - Disability Pension at the Time of Coronary Revascularisation Is Associated with Higher Five-Year Mortality; A Swedish Nationwide, Register-Based Prospective Cohort Study. AB - BACKGROUND: Although coronary revascularisation by coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) are common procedures, little is known regarding disability pension (DP) at the time of coronary revascularisation and its association with mortality. The aim was to investigate the five-year mortality following a first coronary revascularisation among women and men on DP, compared with those not on DP at the time of intervention, accounting for socio-demographic and medical factors. MATERIAL AND METHODS: A nationwide prospective population-based cohort study was conducted, using national registers including 70,040 patients (80% men), aged 30-64 years, with a first CABG (n = 24,987; 36%) or PCI (n = 45,053; 64%) during 1994-2006 in Sweden, who were alive 30 days after the intervention. The main outcome was all cause and cause-specific mortality within five years or through 31 December 2006, following CABG and PCI, and the exposure was DP at the time of a first coronary revascularisation. Information on DP, patient characteristics, date and cause of death was obtained from nationwide registers. Hazard ratios (HR) with 95% confidence intervals (CI) for the outcome were estimated, using Cox proportional hazard regression analyses. All analyses were stratified by type of intervention and gender. FINDINGS: Four percent died following coronary revascularisation. Cardiovascular disease was the most common cause of death (54%), followed by neoplasms (25%). Regardless of type of intervention, gender and after multivariable adjustments, patients on DP had a higher HR for five-year mortality compared with those not on DP at time of revascularisation (CABG: women HR 2.14; 95% CI 1.59-2.89, men HR 2.09; 1.84-2.38, PCI: women HR 2.25; 1.78-2.83, men HR 1.95; 1.72-2.21). Young women on DP at the time of PCI had a substantially higher HR (HR 4.10; 95% CI: 2.25-7.48). CONCLUSION: Patients on DP at the time of first coronary revascularisation had a higher five-year risk of mortality compared with those not on DP. PMID- 26261991 TI - Extracellular Adenosine Formation by Ecto-5'-Nucleotidase (CD73) Is No Essential Trigger for Early Phase Ischemic Preconditioning. AB - BACKGROUND: Adenosine is a powerful trigger for ischemic preconditioning (IPC). Myocardial ischemia induces intracellular and extracellular ATP degradation to adenosine, which then activates adenosine receptors and elicits cardioprotection. Conventionally extracellular adenosine formation by ecto-5'-nucleotidase (CD73) during ischemia was thought to be negligible compared to the massive intracellular production, but controversial reports in the past demand further evaluation. In this study we evaluated the relevance of ecto-5'-nucleotidase (CD73) for infarct size reduction by ischemic preconditioning in in vitro and in vivo mouse models of myocardial infarction, comparing CD73-/- and wild type (WT) mice. METHODS AND RESULTS: 3x5 minutes of IPC induced equal cardioprotection in isolated saline perfused hearts of wild type (WT) and CD73-/- mice, reducing control infarct sizes after 20 minutes of ischemia and 90 minutes of reperfusion from 46 +/- 6.3% (WT) and 56.1 +/- 7.6% (CD73-/-) to 26.8 +/- 4.7% (WT) and 25.6 +/- 4.7% (CD73-/-). Coronary venous adenosine levels measured after IPC stimuli by high-pressure liquid chromatography showed no differences between WT and CD73 /- hearts. Pharmacological preconditioning of WT hearts with adenosine, given at the measured venous concentration, was evenly cardioprotective as conventional IPC. In vivo, 4x5 minutes of IPC reduced control infarct sizes of 45.3 +/- 8.9% (WT) and 40.5 +/- 8% (CD73-/-) to 26.3 +/- 8% (WT) and 22.6 +/- 6.6% (CD73-/-) respectively, eliciting again equal cardioprotection. The extent of IPC-induced cardioprotection in male and female mice was identical. CONCLUSION: The infarct size limiting effects of IPC in the mouse heart in vitro and in vivo are not significantly affected by genetic inactivation of CD73. The ecto-5'-nucleotidase derived extracellular formation of adenosine does not contribute substantially to adenosine's well known cardioprotective effect in early phase ischemic preconditioning. PMID- 26261989 TI - Microbial Ligand Costimulation Drives Neutrophilic Steroid-Refractory Asthma. AB - Asthma is a heterogeneous disease whose etiology is poorly understood but is likely to involve innate responses to inhaled microbial components that are found in allergens. The influence of these components on pulmonary inflammation has been largely studied in the context of individual agonists, despite knowledge that they can have synergistic effects when used in combination. Here we have explored the effects of LPS and beta-glucan, two commonly-encountered microbial agonists, on the pathogenesis of allergic and non-allergic respiratory responses to house dust mite allergen. Notably, sensitization with these microbial components in combination acted synergistically to promote robust neutrophilic inflammation, which involved both Dectin-1 and TLR-4. This pulmonary neutrophilic inflammation was corticosteroid-refractory, resembling that found in patients with severe asthma. Thus our results provide key new insights into how microbial components influence the development of respiratory pathology. PMID- 26261992 TI - Prothrombin Time and Activated Partial Thromboplastin Time Testing: A Comparative Effectiveness Study in a Million-Patient Sample. AB - BACKGROUND: A substantial fraction of all American healthcare expenditures are potentially wasted, and practices that are not evidence-based could contribute to such waste. We sought to characterize whether Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT) tests of preoperative patients are used in a way unsupported by evidence and potentially wasteful. METHODS AND FINDINGS: We evaluated prospectively-collected patient data from 19 major teaching hospitals and 8 hospital-affiliated surgical centers in 7 states (Delaware, Florida, Maryland, Massachusetts, New Jersey, New York, Pennsylvania) and the District of Columbia. A total of 1,053,472 consecutive patients represented every patient admitted for elective surgery from 2009 to 2012 at all 27 settings. A subset of 682,049 patients (64.7%) had one or both tests done and history and physical (H&P) records available for analysis. Unnecessary tests for bleeding risk were defined as: PT tests done on patients with no history of abnormal bleeding, warfarin therapy, vitamin K-dependent clotting factor deficiency, or liver disease; or aPTT tests done on patients with no history of heparin treatment, hemophilia, lupus anticoagulant antibodies, or von Willebrand disease. We assessed the proportion of patients who received PT or aPTT tests who lacked evidence-based reasons for testing. CONCLUSIONS: This study sought to bring the availability of big data together with applied comparative effectiveness research. Among preoperative patients, 26.2% received PT tests, and 94.3% of tests were unnecessary, given the absence of findings on H&P. Similarly, 23.3% of preoperative patients received aPTT tests, of which 99.9% were unnecessary. Among patients with no H&P findings suggestive of bleeding risk, 6.6% of PT tests and 7.1% of aPTT tests were either a false positive or a true positive (i.e. indicative of a previously-undiagnosed potential bleeding risk). Both PT and aPTT, designed as diagnostic tests, are apparently used as screening tests. Use of unnecessary screening tests raises concerns for the costs of such testing and the consequences of false positive results. PMID- 26261993 TI - Identifying Litchi (Litchi chinensis Sonn.) Cultivars and Their Genetic Relationships Using Single Nucleotide Polymorphism (SNP) Markers. AB - Litchi is an important fruit tree in tropical and subtropical areas of the world. However, there is widespread confusion regarding litchi cultivar nomenclature and detailed information of genetic relationships among litchi germplasm is unclear. In the present study, the potential of single nucleotide polymorphism (SNP) for the identification of 96 representative litchi accessions and their genetic relationships in China was evaluated using 155 SNPs that were evenly spaced across litchi genome. Ninety SNPs with minor allele frequencies above 0.05 and a good genotyping success rate were used for further analysis. A relatively high level of genetic variation was observed among litchi accessions, as quantified by the expected heterozygosity (He = 0.305). The SNP based multilocus matching identified two synonymous groups, 'Heiye' and 'Wuye', and 'Chengtuo' and 'Baitangli 1'. A subset of 14 SNPs was sufficient to distinguish all the non redundant litchi genotypes, and these SNPs were proven to be highly stable by repeated analyses of a selected group of cultivars. Unweighted pair-group method of arithmetic averages (UPGMA) cluster analysis divided the litchi accessions analyzed into four main groups, which corresponded to the traits of extremely early-maturing, early-maturing, middle-maturing, and late-maturing, indicating that the fruit maturation period should be considered as the primary criterion for litchi taxonomy. Two subpopulations were detected among litchi accessions by STRUCTURE analysis, and accessions with extremely early- and late-maturing traits showed membership coefficients above 0.99 for Cluster 1 and Cluster 2, respectively. Accessions with early- and middle-maturing traits were identified as admixture forms with varying levels of membership shared between the two clusters, indicating their hybrid origin during litchi domestication. The results of this study will benefit litchi germplasm conservation programs and facilitate maximum genetic gains in litchi breeding programs. PMID- 26261995 TI - Understanding the Halogenation Effects in Diketopyrrolopyrrole-Based Small Molecule Photovoltaics. AB - Two molecules containing a central diketopyrrolopyrrole and two oligothiophene units have been designed and synthesized. Comparisons between the molecules containing terminal F (FDPP) and Cl (CDPP) atoms allowed us to evaluate the effects of halogenation on the photovoltaic properties of the small molecule organic solar cells (OSCs). The OSCs devices employing FDPP:PC71BM films showed power conversion efficiencies up to 4.32%, suggesting that fluorination is an efficient method for constructing small molecules for OSCs. PMID- 26261994 TI - Scriptaid Treatment Decreases DNA Methyltransferase 1 Expression by Induction of MicroRNA-152 Expression in Porcine Somatic Cell Nuclear Transfer Embryos. AB - Abnormal epigenetic reprogramming of donor nuclei after somatic cell nuclear transfer (SCNT) is thought to be the main cause of low cloning efficiencies. A growing body of evidence has demonstrated a positive role of Scriptaid, a histone deacetylase inhibitor (HDACi) that belongs to an existing class of hydroxamic acid-containing HDACis, on the development competence of cloned embryos in many species. The present study investigated the effects of Scriptaid on the development of porcine SCNT embryos in vitro and its mechanism. Treatment with 300 or 500 nM Scriptaid for 20 h after activation significantly increased the percentage of SCNT embryos that developed to the blastocyst stage and the total number of cells per blastocyst and significantly decreased the percentage of apoptotic cells in blastocysts. Scriptaid treatment significantly increased the level of histone H3 acetylated at K9 and the conversion of 5-methylcytosine into 5-hydroxymethylcytosine and significantly decreased the level of histone H3 trimethylated at K9 at the pronuclear stage. As a potential mechanism for the DNA methylation changes, our results showed that the expression of DNA methyltransferase 1 was frequently down-regulated in Scriptaid-treated embryos in comparison with untreated embryos and was inversely correlated to endogenous microRNA-152 (miR-152). Taken together, these findings illustrated a crucial functional crosstalk between miR-152 and DNMT1. Meanwhile, mRNA and protein levels of POU5F1 and CDX2 were increased in Scriptaid-treated embryos. mRNA levels of Caspase3, and Bax were significantly decreased and that of Bcl-xL was significantly increased in Scriptaid-treated embryos. In conclusion, these observations would contribute to uncover the nuclear reprogramming mechanisms underlying the effects of Scriptaid on the improvement of porcine SCNT embryos. PMID- 26261996 TI - Organic-Inorganic Hybrid Solution-Processed H2-Evolving Photocathodes. AB - Here we report for the first time an H2-evolving photocathode fabricated by a solution-processed organic-inorganic hybrid composed of CdSe and P3HT. The CdSe:P3HT (10:1 (w/w)) hybrid bulk heterojunction treated with 1,2-ethanedithiol (EDT) showed efficient water reduction and hydrogen generation. A photocurrent of -1.24 mA/cm(2) at 0 V versus reversible hydrogen electrode (V(RHE)), EQE of 15%, and an unprecedented Voc of 0.85 V(RHE) under illumination of AM1.5G (100 mW/cm(2)) in mild electrolyte were observed. Time-resolved photoluminescence (TRPL), internal quantum efficiency (IQE), and transient photocurrent measurements were carried out to clarify the carrier dynamics of the hybrids. The exciton lifetime of CdSe was reduced by one order of magnitude in the hybrid blend, which is a sign of the fast charge separation upon illumination. By comparing the current magnitude of the solid-state devices and water-splitting devices made with identical active layers, we found that the interfaces of the water-splitting devices limit the device performance. The electron/hole transport properties investigated by comparing IQE spectra upon front- and back-side illumination evidenced balanced electron/hole transport. The Faradaic efficiency is 80-100% for the hybrid photocathodes with Pt catalysts and ~70% for the one without Pt catalysts. PMID- 26261998 TI - Validating the Access to an Electronic Health Record: Classification and Content Analysis of Access Logs. AB - Electronic Health Records (EHRs) have made patient information widely available, allowing health professionals to provide better care. However, information confidentiality is an issue that continually needs to be taken into account. The objective of this study is to describe the implementation of rule-based access permissions to an EHR system. The rules that were implemented were based on a qualitative study. Every time users did not meet the specified requirements, they had to justify access through a pop up window with predetermined options, including a free text option ("other justification"). A secondary analysis of a deidentified database was performed. From a total of 20,540,708 hits on the electronic medical record database, 85% of accesses to the EHR system did not require justification. Content analysis of the "Other Justification" option allowed the identification of new types of access. At the time to justify, however, users may choose the faster or less clicks option to access to EHR, associating the justification of access to the EHR as a barrier. PMID- 26261999 TI - A Practical Approach to Governance and Optimization of Structured Data Elements. AB - Definition and configuration of clinical content in an enterprise-wide electronic health record (EHR) implementation is highly complex. Sharing of data definitions across applications within an EHR implementation project may be constrained by practical limitations, including time, tools, and expertise. However, maintaining rigor in an approach to data governance is important for sustainability and consistency. With this understanding, we have defined a practical approach for governance of structured data elements to optimize data definitions given limited resources. This approach includes a 10 step process: 1) identification of clinical topics, 2) creation of draft reference models for clinical topics, 3) scoring of downstream data needs for clinical topics, 4) prioritization of clinical topics, 5) validation of reference models for clinical topics, and 6) calculation of gap analyses of EHR compared against reference model, 7) communication of validated reference models across project members, 8) requested revisions to EHR based on gap analysis, 9) evaluation of usage of reference models across project, and 10) Monitoring for new evidence requiring revisions to reference model. PMID- 26262000 TI - Systems Architecture for a Nationwide Healthcare System. AB - From a national level to give Internet technology support, the Nationwide Integrated Healthcare System in Uruguay requires a model of Information Systems Architecture. This system has multiple healthcare providers (public and private), and a strong component of supplementary services. Thus, the data processing system should have an architecture that considers this fact, while integrating the central services provided by the Ministry of Public Health. The national electronic health record, as well as other related data processing systems, should be based on this architecture. The architecture model described here conceptualizes a federated framework of electronic health record systems, according to the IHE affinity model, HL7 standards, local standards on interoperability and security, as well as technical advice provided by AGESIC. It is the outcome of the research done by AGESIC and Systems Integration Laboratory (LINS) on the development and use of the e-Government Platform since 2008, as well as the research done by the team Salud.uy since 2013. PMID- 26262001 TI - Electronic Dental Records System Adoption. AB - The use of Electronic Dental Records (EDRs) and management software has become more frequent, following the increase in prevelance of new technologies and computers in dental offices. The purpose of this study is to identify and evaluate the use of EDRs by the dental community in the Sao Paulo city area. A quantitative case study was performed using a survey on the phone. A total of 54 offices were contacted and only one declinedparticipation in this study. Only one office did not have a computer. EDRs were used in 28 offices and only four were paperless. The lack of studies in this area suggests the need for more usability and implementation studies on EDRs so that we can improve EDR adoption by the dental community. PMID- 26262002 TI - Characterizing the Structure of a Patient's Care Team through Electronic Encounter Data Analysis. AB - As the field of medicine grows more complicated and doctors become more specialized in a particular field, the number of healthcare providers involved in healing an individual patient increases. This is particularly true of patients with multiple chronic conditions. Establishing effective communications among the care providers becomes critical to facilitate care coordination and more efficient resource use, which will ultimately result in health outcome improvement. The first step for care coordination is to understand who have been involved in a patient's care and their relationships with the patient. The widespread adoption of Electronic Health Records provides us an opportunity to explore solutions to well-coordinated care. This paper presents the concept of a patient's care team and demonstrates the feasibility of identifying relevant healthcare providers for an individual patient by leveraging electronic patient encounter data. Combined with network analysis techniques, we further visualize the care team structure with quantified strength of patient-provider relationships. Our work is foundational to the larger goal of patient-centered, coordinated care in the digital age of healthcare. PMID- 26262003 TI - An Information Paradigm Shift is Required to Realize EHR Benefits. AB - The use of EHRs and the benefits from them are significant for healthcare and health informatics. Data form the basis for any EHR and its potential to realize these benefits. This paper considers the housing of information and knowledge management in an EHR system. Are we experiencing a revolution in healthcare? Findings from an investigation of alternative approaches, followed by an evaluation of the importance of the adoption of a standard information model relative to benefit realization, is presented. We conclude that an EHR in any environment is not limited to sharing or information exchange. A paradigm shift in thinking, based on the requirement for standardized concept representation, is required. This is an essential prerequisite for a new vision of healthcare supported by digital technologies. PMID- 26262004 TI - Template and Model Driven Development of Standardized Electronic Health Records. AB - Digital patient modeling targets the integration of distributed patient data into one overarching model. For this integration process, both a theoretical standard based model and information structures combined with concrete instructions in form of a lightweight development process of single standardized Electronic Health Records (EHRs) are needed. In this paper, we introduce such a process along side a standard-based architecture. It allows the modeling and implementation of EHRs in a lightweight Electronic Health Record System (EHRS) core. The approach is demonstrated and tested by a prototype implementation. The results show that the suggested approach is useful and facilitates the development of standardized EHRSs. PMID- 26262005 TI - Fast Model Adaptation for Automated Section Classification in Electronic Medical Records. AB - Medical information extraction is the automatic extraction of structured information from electronic medical records, where such information can be used for improving healthcare processes and medical decision making. In this paper, we study one important medical information extraction task called section classification. The objective of section classification is to automatically identify sections in a medical document and classify them into one of the pre defined section types. Training section classification models typically requires large amounts of human labeled training data to achieve high accuracy. Annotating institution-specific data, however, can be both expensive and time-consuming; which poses a big hurdle for adapting a section classification model to new medical institutions. In this paper, we apply two advanced machine learning techniques, active learning and distant supervision, to reduce annotation cost and achieve fast model adaptation for automated section classification in electronic medical records. Our experiment results show that active learning reduces the annotation cost and time by more than 50%, and distant supervision can achieve good model accuracy using weakly labeled training data only. PMID- 26262007 TI - Towards the Implementation of an openEHR-based Open Source EHR Platform (a vision paper). AB - Healthcare Information Systems are a big business. Currently there is an explosion of EHR/EMR products available on the market, and the best tools are really expensive. Many developing countries and healthcare providers cannot access such tools, and for those who can, there is not a clear strategy for the evolution, scaling, and cost of these electronic health products. The lack of standard-based implementations conduct to the creation of isolated information silos that cannot be exploited (i.e. shared between providers to promote a holistic view of each patient's medical history). This paper exposes the main elements behind a Standard-based Open Source EHR Platform that is future-proof and allows to evolve and scale with minimal cost. The proposed EHR Architecture is based on openEHR specifications, adding elements emerged from research and development experiences, leading to a design that can be implemented in any modern technology. Different implementations will be interoperable by design. This Platform will leverage contexts of scarce resources, reusing clinical knowledge, a common set of software components and services. PMID- 26262006 TI - Using EHRs and Machine Learning for Heart Failure Survival Analysis. AB - "Heart failure (HF) is a frequent health problem with high morbidity and mortality, increasing prevalence and escalating healthcare costs" [1]. By calculating a HF survival risk score based on patient-specific characteristics from Electronic Health Records (EHRs), we can identify high-risk patients and apply individualized treatment and healthy living choices to potentially reduce their mortality risk. The Seattle Heart Failure Model (SHFM) is one of the most popular models to calculate HF survival risk that uses multiple clinical variables to predict HF prognosis and also incorporates impact of HF therapy on patient outcomes. Although the SHFM has been validated across multiple cohorts [1 5], these studies were primarily done using clinical trials databases that do not reflect routine clinical care in the community. Further, the impact of contemporary therapeutic interventions, such as beta-blockers or defibrillators, was incorporated in SHFM by extrapolation from external trials. In this study, we assess the performance of SHFM using EHRs at Mayo Clinic, and sought to develop a risk prediction model using machine learning techiniques that applies routine clinical care data. Our results shows the models which were built using EHR data are more accurate (11% improvement in AUC) with the convenience of being more readily applicable in routine clinical care. Furthermore, we demonstrate that new predictive markers (such as co-morbidities) when incorporated into our models improve prognostic performance significantly (8% improvement in AUC). PMID- 26262008 TI - An Ecosystem of Intelligent ICT Tools for Speech-Language Therapy Based on a Formal Knowledge Model. AB - The language and communication constitute the development mainstays of several intellectual and cognitive skills in humans. However, there are millions of people around the world who suffer from several disabilities and disorders related with language and communication, while most of the countries present a lack of corresponding services related with health care and rehabilitation. On these grounds, we are working to develop an ecosystem of intelligent ICT tools to support speech and language pathologists, doctors, students, patients and their relatives. This ecosystem has several layers and components, integrating Electronic Health Records management, standardized vocabularies, a knowledge database, an ontology of concepts from the speech-language domain, and an expert system. We discuss the advantages of such an approach through experiments carried out in several institutions assisting children with a wide spectrum of disabilities. PMID- 26262009 TI - Identification of Patient Safety Risks Associated with Electronic Health Records: A Software Quality Perspective. AB - Although Electronic Health Records (EHR) can offer benefits to the health care process, there is a growing body of evidence that these systems can also incur risks to patient safety when developed or used improperly. This work is a literature review to identify these risks from a software quality perspective. Therefore, the risks were classified based on the ISO/IEC 25010 software quality model. The risks identified were related mainly to the characteristics of "functional suitability" (i.e., software bugs) and "usability" (i.e., interface prone to user error). This work elucidates the fact that EHR quality problems can adversely affect patient safety, resulting in errors such as incorrect patient identification, incorrect calculation of medication dosages, and lack of access to patient data. Therefore, the risks presented here provide the basis for developers and EHR regulating bodies to pay attention to the quality aspects of these systems that can result in patient harm. PMID- 26262010 TI - Nonadherence to Oral Antihyperglycemic Agents: Subsequent Hospitalization and Mortality among Patients with Type 2 Diabetes in Clinical Practice. AB - Using real-world clinical data from the Indiana Network for Patient Care, we analyzed the associations between non-adherence to oral antihyperglycemic agents (OHA) and subsequent diabetes-related hospitalization and all-cause mortality for patients with type 2 diabetes. OHA adherence was measured by the annual proportion of days covered (PDC) for 2008 and 2009. Among 24,067 eligible patients, 35,507 annual PDCs were formed. Over 90% (n=21,798) of the patients had a PDC less than 80%. In generalized linear mixed model analyses, OHA non adherence is significantly associated with diabetes related hospitalizations (OR: 1.2; 95% CI [1.1,1.3]; p<0.0001). Older patients, white patients, or patients who had ischemic heart disease, stroke, or renal disease had higher odds of hospitalization. Similarly, OHA non-adherence increased subsequent mortality (OR: 1.3; 95% CI [1.02, 1.61]; p<0.0001). Patient age, male gender, income and presence of ischemic heart diseases, stroke, and renal disease were also significantly associated with subsequent all-cause death. PMID- 26262011 TI - Validation of Minimum Data of Archetyped Telehealth Clinical Report for Monitoring Prenatal Care. AB - Studies on the validation of minimum data sets from international information standards have drawn the attention of the academic community to the identification of necessary requirements for the development of Electronic Health Records (EHRs). The primary motivation of such studies is the development of systems using archetypes. The aim of this study was to validate the minimum data set that should be used when constructing an archetyped EHR for prenatal care applications in telehealth. In order to achieve this, a data validation tool was built and used by nine expert obstetricians. The statistical analysis employed was the percentage of agreement and the content validity index. The study was conducted in three steps: 1) Literature review, 2)Instrument development, and 3) Validation of the minimum data set. Of the 179 evaluated pieces of data, 157 of them were validated to be included in the archetyped record of the first prenatal consultation, while 56 of them were allocated for the subsequent consultation record. The benefit of this research is the standardization (data validation for an archetyped system) of prenatal care, with the perspective of employing, both nationally and internationally, an archtyped telehealth system. PMID- 26262012 TI - One Million Electrocardiograms of Primary Care Patients: A Descriptive Analysis. AB - In 722 cities of Minas Gerais (Brazil), primary care patients can have their ECGs remotely interpreted by cardiologists of the Telehealth Network of Minas Gerais (TNMG), a public telehealth service. As of December 2014, more than 1.9 million ECGs were interpreted. This study analyzed the database of all ECGs performed by the TNMG on primary care patients from 2009 to 2013 (n=1,101,993). Structured patient data and the results of automated ECG interpretation by the Glasgow Program are described. Mean patient age is 51 years old, 59% of them are women. The average body mass index is 25.9 kg/m2, with an average increase of 0.15 kg/m2 per civil year. Those patients notably have hypertension (33.2%), family history of coronary artery disease (14.5%), smoking (6.9%), diabetes (5.8%), obesity (5.8%) or Chagas Disease (3.0%). Seventy percent of ECGs are normal. This percentage is higher in women (72.3%) and decreases in average by 7.4 every 10 years of life. There are notably 12% of possible myocardial infarction, 10% of possible left ventricular hypertrophy and 8% of possible supraventricular extra systole. PMID- 26262013 TI - ePoint.telemed--An Open Web-based Platform for Home Monitoring of Patients with Chronic Heart Failure. AB - In North Norway, no telemonitoring services for chronic heart failure (CHF) have yet been established, hence no investigations in the area have been published. However, large distances and a sparse population are causes for extra expenditure on hospital visits. In this paper, we describe the ePoint.telemed platform for home telemonitoring of CHF patients. We have reviewed the literature on home monitoring techniques, and developed two prototype platforms for remote collection of physiological data. We have refined one of the prototypes and subjected it to user testing among health professionals and their clients. Fifty patients will be involved in a randomized controlled trial aiming to establish if the home telemonitoring of CHF is clinically feasible and cost-effective. The ePoint.telemed platform is a fully automated internet based system meant for early warnings in a CHF rehabilitation program. The core of the platform is a dashboard connected to a blood pressure meter, a weight scale, and a web-based patient questionnaire. Unlike traditional systems built on dedicated medical equipment, we are applying easy-to-use components geared towards the sports market. PMID- 26262014 TI - Mobile Healthcare System for Health Checkups and Telemedicine in Post-Disaster Situations. AB - Portable Healthcare Clinic (PHC) is a mobile healthcare system comprising of medical sensors and health assessment criteria. It has been applied in Bangladesh for the last two years as a pilot program to identify non-communicable diseases. In this study, we adapted PHC to fit post-disaster conditions. The PHC health assessment criteria are redesigned to deal with emergency cases and healthcare worker insufficiency. A new algorithm makes an initial assessment of age, symptoms, and whether the person is seeing a doctor. These changes will make the turn-around time shorter and will enable reaching the most affected patients better. We tested the operability and turn-around time of the adapted system at the debris flow disaster shelters in Hiroshima, Japan. Changing the PHC health assessment criteria and other solutions such as a list of medicine preparation makes the PHC system switch into an emergency mode more smoothly following a natural disaster. PMID- 26262015 TI - Assessing the Potential Use of Eye-Tracking Triangulation for Evaluating the Usability of an Online Diabetes Exercise System. AB - The Online Diabetes Exercise System was developed to motivate people with Type 2 diabetes to do a 25 minutes low-volume high-intensity interval training program. In a previous multi-method evaluation of the system, several usability issues were identified and corrected. Despite the thorough testing, it was unclear whether all usability problems had been identified using the multi-method evaluation. Our hypothesis was that adding the eye-tracking triangulation to the multi-method evaluation would increase the accuracy and completeness when testing the usability of the system. The study design was an Eye-tracking Triangulation; conventional eye-tracking with predefined tasks followed by The Post-Experience Eye-Tracked Protocol (PEEP). Six Areas of Interests were the basis for the PEEP session. The eye-tracking triangulation gave objective and subjective results, which are believed to be highly relevant for designing, implementing, evaluating and optimizing systems in the field of health informatics. Future work should include testing the method on a larger and more representative group of users and apply the method on different system types. PMID- 26262016 TI - Mobile App to Reduce Inactivity in Sedentary Overweight Women. AB - Recent studies demonstrated that the duration of inactivity (sedentary state) is independently associated with increased risk of cardiovascular disease. Our goal was to develop the technology that can measure the amount of inactivity in real time, remind a person that a preprogrammed period of inactivity has occurred and encourage a period of activity, and provide web-based feedback with tailored information to the participant and investigators. Once it was developed, we carried out a pilot study in a group of sedentary overweight women. The objective of the study was to assess potential of the mobile app to reduce inactivity in our target population. A randomized crossover design was employed with study subjects randomly assigned to a 4-week each "message-on" and "message-off" periods. Out of 30 enrolled subjects, 27 completed the study. The average age of particpants was 52+/-12; BMI: 37+/-6; 47% were white and 47% were African American. Overall, inactivity was significantly lower (p<0.02) during "message on" periods (24.6%) as compared to the "message-off" periods (30.4%). We conluded that mobile app monitoring inactivity and providing a real-time notification when inactivity period exceeds healthy limits was able to significantly reduce inactivity periods in overweight sedentary women. PMID- 26262018 TI - Reconfigurable Embedded System for Electrocardiogram Acquisition. AB - Smartphones include features that offers the chance to develop mobile systems in medical field, resulting in an area called mobile-health. One of the most common medical examinations is the electrocardiogram (ECG), which allows the diagnosis of various heart diseases, leading to preventative measures and preventing more serious problems. The objective of this study was to develop a wireless reconfigurable embedded system using a FPAA (Field Programmable Analog Array), for the acquisition of ECG signals, and an application showing and storing these signals on Android smartphones. The application also performs the partial FPAA reconfiguration in real time (adjustable gain). Previous studies using FPAA usually use the development boards provided by the manufacturer (high cost), do not allow the reconfiguration in real time, use no smartphone and communicate via cables. The parameters tested in the acquisition circuit and the quality of ECGs registered in an individual were satisfactory. PMID- 26262019 TI - Availability Communication: Requirements for an Awareness System to Support Nurses' Handling of Nurse Calls. AB - The recent development of mobile technologies allows nurses to receive different types of requests anywhere. However, the interruptions generated by these devices often presents a challenge for nurses in their daily work in a hospital department. In previous inquires we have investigated nurses' strategies to managing technology-mediated interruptions in the form of nurse calls. This study reports on an effort to co-design a system that supports an important strategy employed by nurses. Through the involvement of domain experts, the study elicits requirements for an awareness system to support nurses' collaborative effort in handling nurse calls. PMID- 26262017 TI - iDECIDE: A Mobile Application for Insulin Dosing Using an Evidence Based Equation to Account for Patient Preferences. AB - Diabetes is a complex disease affecting 29.1 million (9.3%) US citizens [1]. It is a chronic illness that needs continual medical care and ongoing patient self management, education, and support [2]. There is no cure for diabetes, requiring patients to conduct frequent self-monitoring of blood glucose and dosing of insulin in many cases. Evidence has shown that patients are more adherent to their diabetes management plan when they incorporate personal lifestyle choices [3]. To address the challenge of empowering patients to better manage their diabetes, we have developed a novel mobile application prototype, iDECIDE, that refines rapid-acting insulin dose calculations by incorporating two important patient variables in addition to carbohydrates consumed that are not a part of standard insulin dose calculation algorithms: exercise and alcohol intake [4, 5]. A retrospective analysis for the calibration and evaluation of iDECIDE is underway by comparing recommendations made by the application against dosing recommendations made by insulin pumps. PMID- 26262020 TI - Optimizing Decision Support for Tailored Health Behavior Change Applications. AB - The Tailored Lifestyle Change Decision Aid (TLC DA) system was designed to provide support for a person to make an informed choice about which behavior change to work on when multiple unhealthy behaviors are present. TLC DA can be delivered via web, smartphones and tablets. The system collects a significant amount of information that is used to generate tailored messages to consumers to persuade them in certain healthy lifestyles. One limitation is the necessity to collect vast amounts of information from users who manually enter. By identifying an optimal set of self-reported parameters we will be able to minimize the data entry burden of the app users. The study was to identify primary determinants of health behavior choices made by patients after using the system. Using discriminant analysis an optimal set of predictors was identified. The resulting set included smoking status, smoking cessation success estimate, self-efficacy, body mass index and diet status. Predicting smoking cessation choice was the most accurate, followed by weight management. Physical activity and diet choices were better identified in a combined cluster. PMID- 26262021 TI - Towards an Ontology-driven Framework to Enable Development of Personalized mHealth Solutions for Cancer Survivors' Engagement in Healthy Living. AB - Adolescent and Young Adult (AYA) cancer survivors manage an array of health related issues. Survivorship Care Plans (SCPs) have the potential to empower these young survivors by providing information regarding treatment summary, late effects of cancer therapies, healthy lifestyle guidance, coping with work-life health balance, and follow-up care. However, current mHealth infrastructure used to deliver SCPs has been limited in terms of flexibility, engagement, and reusability. The objective of this study is to develop an ontology-driven survivor engagement framework to facilitate rapid development of mobile apps that are targeted, extensible, and engaging. The major components include ontology models, patient engagement features, and behavioral intervention technologies. We apply the proposed framework to characterize individual building blocks ("survivor digilegos"), which form the basis for mHealth tools that address user needs across the cancer care continuum. Results indicate that the framework (a) allows identification of AYA survivorship components, (b) facilitates infusion of engagement elements, and (c) integrates behavior change constructs into the design architecture of survivorship applications. Implications for design of patient-engaging chronic disease management solutions are discussed. PMID- 26262022 TI - A Mobile and Intelligent Patient Diary for Chronic Disease Self-Management. AB - By involving patients in their own long-term care, patient self-management approaches aim to increase self-sufficiency and reduce healthcare costs. For example, electronic patient diaries enable patients to collect health data autonomously, increasing self-reliance and reducing strain on health professionals. By deploying patient diaries on mobile platforms, health data collection can occur at any time and place, increasing the mobility of chronic patients who typically need to enter health data frequently. Importantly, an opportunity also arises for mobile clinical decision support, where health feedback is directly issued to patients without relying on connectivity or remote servers. Regardless of the specific self-management strategy, patient and healthcare provider adoption are crucial. Tailoring the system towards the particular patient and toward institution-specific clinical pathways is essential to increasing acceptance. In this paper we discuss a mobile patient diary realizing both the opportunities and challenges of mobile deployment. PMID- 26262023 TI - Mobile early detection and connected intervention to coproduce better care in severe mental illness. AB - Current approaches to the management of severe mental illness have four major limitations: 1) symptom reporting is intermittent and subject to problems with reliability; 2) service users report feelings of disengagement from their care planning; 3) late detection of symptoms delay interventions and increase the risk of relapse; and 4) care systems are held back by the costs of unscheduled hospital admissions that could have been avoided with earlier detection and intervention. The ClinTouch system was developed to close the loop between service users and health professionals. ClinTouch is an end-to-end secure platform, providing a validated mobile assessment technology, a web interface to view symptom data and a clinical algorithm to detect risk of relapse. ClinTouch integrates high-resolution, continuous longitudinal symptom data into mental health care services and presents it in a form that is easy to use for targeting care where it is needed. The architecture and methodology can be easily extended to other clinical domains, where the paradigm of targeted clinical interventions, triggered by the early detection of decline, can improve health outcomes. PMID- 26262024 TI - Mobile Health Applications, in the Absence of an Authentic Regulation, Does the Usability Score Correlate with a Better Medical Reliability? AB - Health-related mobile applications (apps) have been shown to improve the quality of health and patient care. Their use in clinical and health-related environments is becoming more considerable. The number of health-related apps available for download has considerably increased, while the regulatory position of this new industry is not well known. Despite this lack of regulation, measuring the usability score of these apps is not difficult. We compared two samples of twenty health-related applications each. One of the samples contained the apps with top rated usability scores, and the other contained the apps with lowest-rated usability scores. We found that a good usability score correlates with a better medical reliability of the app's content (p<0.005). In the period in which a valid regulation is still lacking, calculation and attribution of usability scores to mobile applications could be used to identify apps with better medical quality. However, the usability score method ought to be rigorous and should not be rounded off with a simple five stars rating (as is the case in the classic app stores). PMID- 26262025 TI - Towards Improving Hypertensive Patients Care: Pervasive Monitoring and Diagnosis Support. AB - Hypertension is the most common chronic condition dealt with by primary care physicians and other health practitioners. It usually has no symptoms, causing a delay in diagnosis. Moreover, around 20% of the global population suffers from "white-coat syndrome", which can lead to misdiagnosing hypertension. When diagnosed, patients find it difficult to constantly monitor their blood pressure to ensure it is within acceptable levels. In this work, we propose a pervasive solution model for ambulatory monitoring of hypertensive patients and for supporting a clinician with the task of diagnosing hypertension. It contributes to the selection of attributes and techniques for assisting hypertension diagnosis, and also to an implementation which dynamically adjusts itself to each patient's average blood pressure. PMID- 26262026 TI - E-Patient Reputation in Health Forums. AB - Online health forums are increasingly used by patients to get information and help related to their health. However, information reliability in these forums is unfortunately not always guaranteed. Obviously, consequences of self-diagnosis may be severe on the patient's health if measures are taken without consulting a doctor. Many works on trust issues related to social media have been proposed, but most of them mainly focus only on the structure part of the social network (number of posts, number of likes, etc.). In the case of online health forums, a lot of trust and distrust is expressed inside the posted messages and cannot be inferred by only considering the structure. In this study, we rather suggest inferring the user's trustworthiness from the replies he receives in the forum. The proposed method is divided into three main steps: First, the recipient(s) of each post must be identified. Next, the trust or distrust expressed in these posts is evaluated. Finally, the user's reputation is computed by aggregating all the posts he received. Conducted experiments using a manually annotated corpus are encouraging. PMID- 26262027 TI - Web-based Self-management Support Interventions for Cancer Survivors: A Systematic Review and Meta-analyses. AB - Those who are living with cancer as a chronic disease need to self-manage the late and long-term effects of cancer and its treatment. We conducted systematic searches of English-language peer-reviewed publications in PubMed, Cumulative Index for Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, and EMBASE between January 2000 and June 2014. We searched for web-based interventions designed to help cancer survivors manage their symptoms and the side effects of cancer treatments, which yielded 37 studies that were systematically reviewed. For the meta-analyses, five articles were selected for fatigue, seven for depression, five for anxiety, and five for overall quality of life. The most popular mode of intervention delivery was "peer-to-peer access" in the communicative functions category, followed by "the use of an enriched information environment" in the automated functions category. The effectss across all outcome measures were small to moderate compared to standard care. Healthcare providers could use information technologies to support self-management among cancer survivors based on their needs across the cancer care continuum. PMID- 26262028 TI - The Shared Decision Making Frontier: a Feasibility and Usability Study for Managing Non-Critical Chronic Illness by Combining Behavioural & Decision Theory with Online Technology. AB - The objective of this study is to determine if shared decisions for managing non critical chronic illness, made through an online biomedical technology intervention, us feasible and usable. The technology intervention incorporates behavioural and decision theories to increase patient engagement, and ultimately long term adherence to health behaviour change. We devised the iheart web intervention as a "proof of concept" in five phases. The implementation incorporates the Vaadin web application framework, Drools, EclipseLink and a MySQL database. Two-thirds of the study participants favoured the technology intervention, based on Likert-scale questions from a post-study questionnaire. Qualitative analysis of think aloud feedback, video screen captures and open ended questions from the post-study questionnaire uncovered six main areas or themes for improvement. We conclude that online shared decisions for managing a non-critical chronic illness are feasible and usable through the iheart web intervention. PMID- 26262029 TI - Experiences of Healthcare Professionals to the Introduction in Sweden of a Public eHealth Service: Patients' Online Access to their Electronic Health Records. AB - Patients' increasing demands for medical information, the digitization of health records and the fast spread of Internet access form a basis of introducing new eHealth services. An international trend is to provide access for patients to health information of various kind. In Sweden, access by patients to their proper electronic health record (EHR) has been provided in a pilot county since November 2012. This eHealth service is controversial and criticism has arised from the clinical professions, mainly physicians. Two web surveys were conducted to discover whether the opinions of healthcare professionals differ; between staff that have had experience with patients accessing their own EHR and those who have no such expericence. Experienced nurses found the EHR more important for the patients and a better reform, compared to unexperienced nurses in the rest of the country. Similarly, physicians with their own experience had a more positive attitude compared to non-experienced physicians. The conclusion of this study is that healthcare professionals must be involved in the implementation of public eHealth services such as EHRs and that real experiences of the professionals should be better disseminated to their inexperienced peers. PMID- 26262030 TI - Characterizing Patient-Generated Clinical Data and Associated Implications for Electronic Health Records. AB - Patient-facing technologies are increasingly utilized for direct patient data entry for potential incorporation into the electronic health record. We analyzed patient-entered data during implementation of a patient-facing data entry technology using an online patient portal and clinic-based tablet computers at a University-based tertiary medical center clinic, including entries for past medical history, past surgical history, and social history. Entries were assessed for granularity, clinical accuracy, and the addition of novel information into the record. We found that over half of patient-generated diagnoses were duplicates of lesser or equal granularity compared to previous provider-entered diagnoses. Approximately one fifth of patient-generated diagnoses were found to meet the criteria for new, meaningful additions to the medical record. Our findings demonstrate that while patient-generated data provides important additional information, it may also present challenges including generating inaccurate or less granular information. PMID- 26262031 TI - Recognizing Clinical Styles in a Dental Surgery Simulator. AB - Recognizing clinical style is essential for generating intelligent guidance in virtual reality simulators for dental skill acquisition. The aim of this study was to determine the potential of Dynamic Time Warping (DTW) in matching novices' tooth cutting sequences with those of experts. Forty dental students and four expert dentists were enrolled to perform access opening to the root canals with a simulator. Four experts performed in manners that differed widely in the tooth preparation sequence. Forty students were randomly allocated into four groups and were trained following each expert. DTW was performed between each student's sequence and all the expert sequences to determine the best match. Overall, the accuracy of the matching was high (95%). The current results suggest that the DTW is a useful technique to find the best matching expert for a student so that feedback based on that expert's performance can be given to the novice in clinical skill training. PMID- 26262032 TI - Web-based auditory self-training system for adult and elderly users of hearing aids. AB - INTRODUCTION: Adults and elderly users of hearing aids suffer psychosocial reactions as a result of hearing loss. Auditory rehabilitation is typically carried out with support from a speech therapist, usually in a clinical center. For these cases, there is a lack of computer-based self-training tools for minimizing the psychosocial impact of hearing deficiency. OBJECTIVE: To develop and evaluate a web-based auditory self-training system for adult and elderly users of hearing aids. METHODS: Two modules were developed for the web system: an information module based on guidelines for using hearing aids; and an auditory training module presenting a sequence of training exercises for auditory abilities along the lines of the auditory skill steps within auditory processing. We built aweb system using PHP programming language and a MySQL database .from requirements surveyed through focus groups that were conducted by healthcare information technology experts. The web system was evaluated by speech therapists and hearing aid users. An initial sample of 150 patients at DSA/HRAC/USP was defined to apply the system with the inclusion criteria that: the individuals should be over the age of 25 years, presently have hearing impairment, be a hearing aid user, have a computer and have internet experience. They were divided into two groups: a control group (G1) and an experimental group (G2). These patients were evaluated clinically using the HHIE for adults and HHIA for elderly people, before and after system implementation. A third web group was formed with users who were invited through social networks for their opinions on using the system. A questionnaire evaluating hearing complaints was given to all three groups. The study hypothesis considered that G2 would present greater auditory perception, higher satisfaction and fewer complaints than G1 after the auditory training. It was expected that G3 would have fewer complaints regarding use and acceptance of the system. RESULTS: The web system, which was named SisTHA portal, was finalized, rated by experts and hearing aid users and approved for use. The system comprised auditory skills training along five lines: discrimination; recognition; comprehension and temporal sequencing; auditory closure; and cognitive-linguistic and communication strategies. Users needed to undergo auditory training over a minimum period of 1 month: 5 times a week for 30 minutes a day. Comparisons were made between G1 and G2 and web system use by G3. CONCLUSION: The web system developed was approved for release to hearing aid users. It is expected that the self-training will help improve effective use of hearing aids, thereby decreasing their rejection. PMID- 26262033 TI - Design, Implementation and Evaluation of an Architecture based on the CDA R2 Document Repository to Provide Support to the Contingency Plan. AB - The pervasive use of electronic records in healthcare increases the dependency on technology due to the lack of physical backup for the records. Downtime in the Electronic Health Record system is unavoidable, due to software, infrastructure and power failures as well as natural disasters, so there is a need to develop a contingency plan ensuring patient care continuity and minimizing risks for health care delivery. To mitigate these risks, two applications were developed allowing healthcare delivery providers to retrieve clinical information using the Clinical Document Architecture Release 2 (CDA R2) document repository as the information source. In this paper we describe the strategy, implementation and results; and provide an evaluation of effectiveness. PMID- 26262034 TI - Archetype based patient data modeling to support treatment of pituitary adenomas. AB - The treatment of patients with pituitary adenoma requires the assessment of various patient data by the clinician. Because of their heterogeneity, they are stored in different sub-information systems, limiting a fast and easy access. The objective of this paper is to apply and test the tools provided by the openEHR Foundation to model the patient data relevant for diagnosis and treatment of the disease with the future intention to implement a centralised standard-based information platform. This platform should support the clinician in the treatment of the disease and improve the information exchange with other healthcare institutions. Some results of the domain modeling, so far obtained, are presented, and the advantages of openEHR emphasized. The free tools and the large database of existing structured and standard archetypes facilitated the modeling task. The separation of the domain modeling from the application development will support the next step of development of the information platform. PMID- 26262035 TI - Evaluating Business Value of IT in Healthcare: Three Clinical Practices from Australia and the US. AB - Exponentially increasing costs in healthcare coupled with poor quality and limited access have motivated the healthcare industry to turn to IS/IT solutions to overcome these issues and facilitate superior healthcare delivery. In an environment of rapid development of new clinical informatics solutions claiming to provide better healthcare delivery, there is a paucity of systematic frameworks to robustly measure the actual value of these systems. The promised business value of these solutions has been elusive; hence, this study offers an approach for the evaluation of the business value of health IS/IT solutions based on a conceptual model, which has been validated using three clinical case studies. PMID- 26262036 TI - Toward User-Centered Patient Safety Event Reporting System: A Trial of Text Prediction in Clinical Data Entry. AB - As a primary source for learning from lessons, patient safety event reporting systems have been widely adopted. Nevertheless, underreporting and low quality of reports pervade the system. To address these issues, the study proposed two text prediction functions as data entry aids to system users. With 52 subjects, a two group randomized experiment was conducted to quantify the impacts in terms of the reporting efficiency, quality, and usability attitudes. Consequentially, on structured data entry, the results were an overall 13.0% time reduction and 3.9% increase of response accuracy with the functions; on unstructured data entry, there was an overall 70.5% increase in the text generation rate, a 34.1% increase in the reporting completeness score, and a 14.5% reduction on the amount of text fields ignored by subjects. Subjects' usability attitudes were slightly improved with the proposed functions according to the questionnaire results. PMID- 26262037 TI - The Role of Hospital Information Systems in Universal Health Coverage Monitoring in Rwanda. AB - In this retrospective study, the authors monitored the patient health coverage in 6 Rwandan hospitals in the period between 2011 and 2014. Among the 6 hospitals, 2 are third level hospitals, 2 district hospitals and 2 private hospitals. Patient insurance and financial data were extracted and analyzed from OpenClinic GA, an open source hospital information system (HIS) used in those 6 hospitals. The percentage of patients who had no health insurer globally decreased from 35% in 2011 to 15% in 2014. The rate of health insurance coverage in hospitals varied between 75% in private hospitals and 84% in public hospitals. The amounts paid by the patients for health services decreased in private hospitals to 25% of the total costs in 2014 (-7.4%) and vary between 14% and 19% in public hospitals. Although the number of insured patients has increased and the patient share decreased over the four years of study, the patients' out-of-pocket payments increased especially for in-patients. This study emphasizes the value of integrated hospital information systems for this kind of health economics research in developing countries. PMID- 26262038 TI - Bluetooth Roaming for Sensor Network System in Clinical Environment. AB - A sensor network is key infrastructure for advancing a hospital information system (HIS). The authors proposed a method to provide roaming functionality for Bluetooth to realize a Bluetooth-based sensor network, which is suitable to connect clinical devices. The proposed method makes the average response time of a Bluetooth connection less than one second by making the master device repeat the inquiry process endlessly and modifies parameters of the inquiry process. The authors applied the developed sensor network for daily clinical activities in an university hospital, and confirmed the stabilitya and effectiveness of the sensor network. As Bluetooth becomes a quite common wireless interface for medical devices, the proposed protocol that realizes Bluetooth-based sensor network enables HIS to equip various clinical devices and, consequently, lets information and communication technologies advance clinical services. PMID- 26262039 TI - On Building an Ontological Knowledge Base for Managing Patient Safety Events. AB - Over the past decade, improving healthcare quality and safety through patient safety event reporting systems has drawn much attention. Unfortunately, such systems are suffering from low data quality, inefficient data entry and ineffective information retrieval. For improving the systems, we develop a semantic web ontology based on the WHO International Classification for Patient Safety (ICPS) and AHRQ Common Formats for patient safety event reporting. The ontology holds potential in enhancing knowledge management and information retrieval, as well as providing flexible data entry and case analysis for both reporters and reviewers of patient safety events. In this paper, we detailed our efforts in data acquisition, transformation, implementation and initial evaluation of the ontology. PMID- 26262040 TI - Case Study: Applying OpenEHR Archetypes to a Clinical Data Repository in a Chinese Hospital. AB - openEHR is a flexible and scalable modeling methodology for clinical information and has been widely adopted in Europe and Australia. Due to the reasons of differences in clinical process and management, there are few research projects involving openEHR in China. To investigate the feasibility of openEHR methodology for clinical information modelling in China, this paper carries out a case study to apply openEHR archetypes to Clinical Data Repository (CDR) in a Chinese hospital. The results show that a set of 26 archetypes are found to cover all the concepts used in the CDR. Of all these, 9 (34.6%) are reused without change, 10 are modified and/or extended, and 7 are newly defined. The reasons for modification, extension and newly definition have been discussed, including granularity of archetype, metadata-level versus data-level modelling, and the representation of relationships between archetypes. PMID- 26262041 TI - Quality indicators from laboratory and radiology information systems. AB - Consequences of the computerization of laboratory and radiology information system (LIS and RIS) are not well documented. The aim of this study was to evaluate the impact of computerization of LIS and RIS of four hospitals on performance and quality of care. The study was divided into three phases. First, the subprocesses and information flows of LIS and RIS were described. Then, a literature review was performed in order to identify the indicators used to assess the impact of computerization. Finally, comparisons were made between 2 hospitals. Using the initial framework, each partner described its process mapping concerning LIS and RIS. The review identified a wide panel of indicators. Only 41 were useful to assess the impact of information systems. For each two by two comparison, lists of relevant indicators have been selected from the identified indicators and according to the process mapping comparison. Two by two comparisons have to be completed. Eventually, these indicators may be integrated in the quality process of hospital information systems. PMID- 26262042 TI - Building a Semantic Interoperability Framework for Care and Research in Fibromuscular Dysplasia. AB - Identifying patients with Fibromuscular Dysplasia (FMD) at the international level will have considerable value for understanding the epidemiology, clinical manifestations and susceptible genes in this arterial disease, but also for identifying eligible patients in clinical trials or cohorts. We present a two step methodology to create a general semantic interoperability framework allowing access and comparison of distributed data over various nations, languages, formats and databases. METHODS: The first step is to develop a pivot multidimensional model based on a core dataset to harmonize existing heterogeneous data sources. The second step is to align the model to additional data, semantically related to FMD and collected currently in various registries. We present the results of the first step that has been fully completed with the validation and implementation of the model in a dedicated information system (SIR FMD). We discuss the current achievements for step 2 and the extensibility of the methodology in the context of other rare diseases. PMID- 26262043 TI - Micro- and Macrointegration Profiles for Medical Devices and Medical IT Systems. AB - Collecting, saving, and providing patient data are essential processes of documentation in a hospital. Many IT systems have evolved to provide solutions in this area. The automatic transfer of medical device data to these information systems is a new challenge for hospital IT systems. Some vendors are focused on the integration of medical IT systems and medical devices. They provide great solutions with magnificent features. Nevertheless, those integration solutions are proprietary and isolated, limiting the operator's selection of his medical devices and medical IT systems. Standardizing communication processes within the operating room and between medical devices and medical IT systems brings benefits for both patient and hospital staff. This work identifies and proposes micro- and macrointegration profiles as a basis for new IHE Integration Profiles for both medical IT systems and medical devices of the operating room. PMID- 26262044 TI - Product-based Safety Certification for Medical Devices Embedded Software. AB - Worldwide medical device embedded software certification practices are currently focused on manufacturing best practices. In Brazil, the national regulatory agency does not hold a local certification process for software-intensive medical devices and admits international certification (e.g. FDA and CE) from local and international industry to operate in the Brazilian health care market. We present here a product-based certification process as a candidate process to support the Brazilian regulatory agency ANVISA in medical device software regulation. Center of Strategic Technology for Healthcare (NUTES) medical device embedded software certification is based on a solid safety quality model and has been tested with reasonable success against the Class I risk device Generic Infusion Pump (GIP). PMID- 26262045 TI - Patient Safety at Transitions of Care: Use of a Compulsory Electronic Reconciliation Tool in an Academic Hospital. AB - Medication errors are responsible for most inpatient adverse events. Medication reconciliation emerged as an effective strategy to decrease these problems, enhancing patient safety. Electronic health records with reconciliation tools could improve the process, but many aspects should be considered in order to reach expected outcomes. In this paper we analyzed how a compulsory, electronic reconciliation application was used at Hospital Italiano in Buenos Aires, through admission and discharge processes. We evaluated all medications that were reconciled during patient admission and discharge since its implementation, from February to November 2014. During that period, there were 78,714 reconciled medications regarding 37,741 admissions (2.08 reconciled medications per hospitalization), of 27,375 patients (2.88 medications per patient). At admission, 63% of medications were confirmed and the remaining were paused or deleted. At discharge, 41% of all medications were reconfirmed. In the creation of the best possible medication history, the use of an electronic reconciliation tool would clean overloaded lists, but at the same time medications could be erroneously deleted. PMID- 26262046 TI - Lead User Design: Medication Management in Electronic Medical Records. AB - Improvements in medication management may lead to a reduction of preventable errors. Usability and user experience issues are common and related to achieving benefits of Electronic Medical Records (EMRs). This paper reports on a novel study that combines the lead user method with a safety engineering review to discover an innovative design for the medication management module in EMRs in primary care. Eight lead users were recruited that represented prescribers and clinical pharmacists with expertise in EMR design, evidence-based medicine, medication safety and medication research. Eight separate medication management module designs were prototyped and validated, one with each lead user. A parallel safety review of medicaiton management was completed. The findings were synthesized into a single common set of goals, activities and one interactive, visual prototype. The lead user method with safety review proved to be an effective way to elicit diverse user goals and synthesize them into a common design. The resulting design ideas focus on meeting the goals of quality, efficiency, safety, reducing the cognitive load on the user, and improving communication wih the patient and the care team. Design ideas are being adapted to an existing EMR product, providing areas for further work. PMID- 26262047 TI - High Override Rate for Opioid Drug-allergy Interaction Alerts: Current Trends and Recommendations for Future. AB - This study examined trends in drug-allergy interaction (DAI) alert overrides for opioid medications - the most commonly triggered alerts in the computerized provider order entry (CPOE). We conducted an observational analysis of the DAI opioid alerts triggered over the last decade (2004-2013, n=342,338) in two large academic hospitals in Boston (United States). We found an increasing rate of DAI alert overrides culminating in 89.7% in 2013. Allergic reactions included a high proportion (38.2%) of non-immune mediated opioid reactions (e.g. gastrointestinal upset). The DAI alert override rate was high for immune mediated (88.6%) and life threatening reactions (87.8%). Exact allergy-medication matches were overridden less frequently (about 70%) compared to non-exact matches within allergy groups (over 90%). About one-third of the alert override reasons pointed to irrelevant alerts (i.e."Patient has tolerated the medication before") and 44.9% were unknown. Those findings warrant further investigation into providers' reasons for high override rate. User interfaces should evolve to enable less interruptive and more accurate alerts to decrease alert fatigue. PMID- 26262048 TI - Usability Testing of PROCEnf-USP: A Clinical Decision Support System. AB - Decision support systems (DSSs) are recognized as important tools, capable of processing high volumes of data and increasing productivity. The usability of these tools affects their effectiveness. By evaluating the interactions between registered nurses (RNs) and the DSSs, this study explores how they impact RN decision-making. This study analyzed 24 months (2011-2012) of data collected in Brazil in two units of a large, public, urban hospital in Sao Paulo that uses a nurse documentation system with an embedded DSS based on NANDA-I. Using mixed effects logistic regression, this study analyzed the agreement between RNs and a DSS when selecting nursing diagnoses. Results suggest that the agreement is mediated by characteristics of the RNs (education and experience) as well as units and year of encounter. Surprisingly, disagreement between RN and DSS when selecting defining characteristics (DC) had positive effects on the odds of agreement on diagnoses. Our results suggest that DSSs support nurses' clinical decision making, but the nurse's clinical judgment is the mediating factor. More research is necessary. PMID- 26262049 TI - Patient Safety in Critical Care Unit: Development of a Nursing Quality Indicator System. AB - This is a methodological study and technological production that aims to describe the development of a computerized system of nursing care quality indicators for the Intensive Care Unit. The study population consisted of a systems analyst and fifteen critical care nurses. For the development of the system we adopted some of the best practices of the Unified Process methodology using the Unified Modeling Language and the programming language Java Enterprise Edition 7. The system consists of an access menu with the following functions: Home (presents general information), New Record (records the indicator), Record (record search), Census (add information and indicators of the patient), Report (generates report of the indicators) and Annex (accesses the Braden Scale). This information system allows for measurement of the quality of nursing care and to evaluate patient safety in intensive care unit by monitoring quality indicators in nursing. PMID- 26262050 TI - Pre-Implementation Study of a Nursing e-Chart: How Nurses Use Their Time. AB - In clinical practice, nurses perform different activities that exceed direct care of patients, and influence workload and time administration among different tasks. When implementing changes in an electronic nursing record, it is important to measure how it affects the time committed to documentation. The objective of this study was to determine the time dedicated to different activities, including those related to electronic documentation prior to implementing a redesigned nurse chart in an Electronic Health Record at the Hospital Italiano de Buenos Aires. An observational work sampling study was performed. Nursing activities observed were categorized as direct care, indirect care, support, non-patient related, and personal activities. During the study, 74 nurses were observed and 2,418 observations were made in the Intensive Care Unit (32.22%), the Intermediate Care Unit (29.57%), and the General Care Unit (38.21%). Nurses' activities included 37.40% of direct care, 41.18% of indirect care, 0.43% support tasks, 11.14% non-related to patient tasks, and 9.77% personal activities. The results allow for the estimation of the impact of a nursing e-chart on nurses' activities, workflow and patient care. PMID- 26262051 TI - Web-tool to Support Medical Experts in Probabilistic Modelling Using Large Bayesian Networks With an Example of Hinosinusitis. AB - For many complex diseases, finding the best patient-specific treatment decision is difficult for physicians due to limited mental capacity. Clinical decision support systems based on Bayesian networks (BN) can provide a probabilistic graphical model integrating all necessary aspects relevant for decision making. Such models are often manually created by clinical experts. The modeling process consists of graphical modeling conducted by collecting of information entities, and probabilistic modeling achieved through defining the relations of information entities to their direct causes. Such expert-based probabilistic modelling with BNs is very time intensive and requires knowledge about the underlying modeling method. We introduce in this paper an intuitive web-based system for helping medical experts generate decision models based on BNs. Using the tool, no special knowledge about the underlying model or BN is necessary. We tested the tool with an example of modeling treatment decisions of Rhinosinusitis and studied its usability. PMID- 26262052 TI - Physicians' Attitudes Towards the Advice of a Guideline-Based Decision Support System: A Case Study With OncoDoc2 in the Management of Breast Cancer Patients. AB - When wrongly used, guideline-based clinical decision support systems (CDSSs) may generate inappropriate propositions that do not match the recommendations provided by clinical practice guidelines (CPGs). The user may decide to comply with or react to the CDSS, and her decision may finally comply or not with CPGs. OncoDoc2 is a guideline-based CDSS for breast cancer management. We collected 394 decisions made by multidisciplinary meeting physicians in three hospitals where the CDSS was evaluated. We observed a global CPG compliance of 86.8% and a global CDSS compliance of 75.4%. Non-CPG compliance was observed in case of a negative reactance to the CDSS, when users did not follow a correct CDSS proposition (8.6% of decisions). Because of errors in patient data entry, OncoDoc2 delivered non recommended propositions in 21.3% of decisions, leading to compliances with CDSS and CPGs of respectively 21.4% and 65.5%, whereas both compliances exceeded 90% when CDSS advices included CPG recommendations. Automation bias, when users followed an incorrect CDSS proposition explained the remaining non-compliance with CPGs (4.6% of decisions). Securing the use of CDSSs is of major importance to warranty patient safety and benefit of their potential to improve care. PMID- 26262053 TI - Use of a Proven Framework for Computer Decision Support within the Intermountain Healthcare Network. AB - Hospitalized patients in the U.S. do not always receive optimal care. In light of this, Computerized Decision Support (CDS) has been recommended to for the improvement of patient care. A number of methodologies, standards, and frameworks have been developed to facilitate the development and interoperability of computerized clinical guidelines and CDS logic. In addition, Health Information Exchange using Service-Oriented Architecture holds some promise to help realize that goal. We have used a framework at Intermountain Healthcare that employs familiar programming languages and technology to develop over 40 CDS applications during the past 13 years, which clinicians are dependent on each day. This paper describes the framework, technology, and CDS application development methods, while providing three distinct examples of applications that illustrate the need and use of the framework for patient care improvement. The main limitation of this framework is its dependence on point-to-point interfaces to access patient data. We look forward to the use of validated and accessible Service-Oriented Architecture to facilitate patient data access across diverse databases. PMID- 26262054 TI - An Ontology-Based Clinical Decision Support System for the Management of Patients with Multiple Chronic Disorders. AB - Decision support systems, as means of disseminating clinical practice guidelines, are powerful software that may lead to an improvement of medical practices. However, they are not always efficient and may suffer from limitations among which are lack of flexibility and weaknesses in the integration of several clinical practice guidelines (CPGs) for the management of patients with multiple chronic disorders. We propose a framework based on an ontological modeling of CPG contents as rules. The ontology provides the required flexibility to adapt patient data and enable the provision of appropriate recommendations expressed at various levels of abstraction. To solve decisional conflicts that occur when combining multiple sources of recommendations, we proposed a method based on the subsumption graph of the patient profiles corresponding to the rules. A prototype CDSS implementing this approach has been developed. Results are given on a clinical case to illustrate the assets of ontological reasoning in increasing the number of issued recommendations and thereby the reliability of decision support. PMID- 26262055 TI - Understanding Deviations from Clinical Practice Guidelines in Adult Soft Tissue Sarcoma. AB - In recent years we have witnessed the increasing adoption of clinical practice guidelines (CPGs) as decision support tools that guide medical treatment. As CPGs gain popularity, it has become evident that physicians frequently deviate from CPG recommendations, both erroneously and due to sound medical rationale. In this study we developed a methodology to computationally identify these deviation cases and understand their movitation. This was achieved using an integrated approach consisting of natural language processing, data modeling, and comparison methods to characterize deviations from CPG recommendations for 1431 adult soft tissue sarcoma patients. The results show that 48.9% of patient treatment programs deviate from CPG recommendations, with the largest deviation type being overtreatment, followed by differences in drug treatments. Interestingly, we identified over a dozen potential reasons for these deviations, with those directly related to the patients' cancer status being most abundant. These findings can be used to modify CPGs, increase adherence to CPG recommendations, reduce treatment cost, and potentially impact sarcoma care. Our approach can be applied to additional diseases that are subject to high deviation levels from CPGs. PMID- 26262056 TI - INITIATE: An Intelligent Adaptive Alert Environment. AB - Exposure to a large volume of alerts generated by medical Alert Generating Systems (AGS) such as drug-drug interaction softwares or clinical decision support systems over-whelms users and causes alert fatigue in them. Some of alert fatigue effects are ignoring crucial alerts and longer response times. A common approach to avoid alert fatigue is to devise mechanisms in AGS to stop them from generating alerts that are deemed irrelevant. In this paper, we present a novel framework called INITIATE: an INtellIgent adapTIve AlerT Environment to avoid alert fatigue by managing alerts generated by one or more AGS. We have identified and categories the lifecycle of different alerts and have developed alert management logic as per the alerts' lifecycle. Our framework incorporates an ontology that represents the alert management strategy and an alert management engine that executes this strategy. Our alert management framework offers the following features: (1) Adaptability based on users' feedback; (2) Personalization and aggregation of messages; and (3) Connection to Electronic Medical Records by implementing a HL7 Clinical Document Architecture parser. PMID- 26262057 TI - Influence Diagram As a Support Tool for Clinical Decisions In Cardiopulmonary And Metabolic Rehabilitation. AB - An influence diagram (ID) is a method of graphical representation of uncertain knowledge, which can be employed to support decisions in health care using probabilistic reasoning. We aimed to describe the development of an ID to support the decision-making process in phase II at Cardiopulmonary and Metabolic Rehabilitation Program (CPMR). The development of the ID was carried out through the identification of relevant variables and their possible values, as well as the identification of details of each variable, in order to find a network structure that appropriately connects the nodes that represent the variables, with arcs linking acyclic graphs, and to build the graph using specialized knowledge and the conditional probability table for each node in the graph. In spite of the complexity of the interactions, the model obtained with the ID seems to contribute in the decision-making process in phase II CPMR, providing a second opinion to the health pratictioner and helping in diagnostic, therapeutic and decision-making processes, since it is useful in situations with non-linear modeling or with absent or uncertain information. PMID- 26262058 TI - Advances In Infection Surveillance and Clinical Decision Support With Fuzzy Sets and Fuzzy Logic. AB - By the use of extended intelligent information technology tools for fully automated healthcare-associated infection (HAI) surveillance, clinicians can be informed and alerted about the emergence of infection-related conditions in their patients. Moni--a system for monitoring nosocomial infections in intensive care units for adult and neonatal patients--employs knowledge bases that were written with extensive use of fuzzy sets and fuzzy logic, allowing the inherent un sharpness of clinical terms and the inherent uncertainty of clinical conclusions to be a part of Moni's output. Thus, linguistic as well as propositional uncertainty became a part of Moni, which can now report retrospectively on HAIs according to traditional crisp HAI surveillance definitions, as well as support clinical bedside work by more complex crisp and fuzzy alerts and reminders. This improved approach can bridge the gap between classical retrospective surveillance of HAIs and ongoing prospective clinical-decision-oriented HAI support. PMID- 26262059 TI - A Decision Fusion Framework for Treatment Recommendation Systems. AB - Treatment recommendation is a nontrivial task--it requires not only domain knowledge from evidence-based medicine, but also data insights from descriptive, predictive and prescriptive analysis. A single treatment recommendation system is usually trained or modeled with a limited (size or quality) source. This paper proposes a decision fusion framework, combining both knowledge-driven and data driven decision engines for treatment recommendation. End users (e.g. using the clinician workstation or mobile apps) could have a comprehensive view of various engines' opinions, as well as the final decision after fusion. For implementation, we leverage several well-known fusion algorithms, such as decision templates and meta classifiers (of logistic and SVM, etc.). Using an outcome-driven evaluation metric, we compare the fusion engine with base engines, and our experimental results show that decision fusion is a promising way towards a more valuable treatment recommendation. PMID- 26262060 TI - Health Care Decision Support System for the Pediatric Emeregency Department Management. AB - Health organization management is facing a high amount of complexity due to the inherent dynamics of the processes and the distributed organization of hospitals. It is therefore necessary for health care institutions to focus on this issue in order to deal with patients' requirements and satisfy their needs. The main objective of this study is to develop and implement a Decision Support System which can help physicians to better manage their organization, to anticipate the overcrowding feature, and to establish avoidance proposals for it. This work is a part of HOST project (Hospital: Optimization, Simulation, and Crowding Avoidance) of the French National Research Agency (ANR). It aims to optimize the functioning of the Pediatric Emergency Department characterized by stochastic arrivals of patients which leads to its overcrowding and services overload. Our study is a set of tools to smooth out patient flows, enhance care quality and minimize long waiting times and costs due to resources allocation. So we defined a decision aided tool based on Multi-agent Systems where actors negotiate and cooperate under some constraints in a dynamic environment. These entities which can be either physical agents representing real actors in the health care institution or software agents allowing the implementation of optimizing tools, cooperate to satisfy the demands of patients while respecting emergency degrees. This paper is concerned with agents' negotiation. It proposes a new approach for multi-skill tasks scheduling based on interactions between agents. PMID- 26262061 TI - Analysis of Hospital Processes with Process Mining Techniques. AB - Process mining allows for discovery, monitoring, and improving processes identified in information systems from their event logs. In hospital environments, process analysis has been a crucial factor for cost reduction, control and proper use of resources, better patient care, and achieving service excellence. This paper presents a new component for event logs generation in the Hospital Information System or HIS, developed at University of Informatics Sciences. The event logs obtained are used for analysis of hospital processes with process mining techniques. The proposed solution intends to achieve the generation of event logs in the system with high quality. The performed analyses allowed for redefining functions in the system and proposed proper flow of information. The study exposed the need to incorporate process mining techniques in hospital systems to analyze the processes execution. Moreover, we illustrate its application for making clinical and administrative decisions for the management of hospital activities. PMID- 26262062 TI - Improving Hospital-Wide Early Resource Allocation through Machine Learning. AB - The objective of this paper is to evaluate the extent to which early determination of diagnosis-related groups (DRGs) can be used for better allocation of scarce hospital resources. When elective patients seek admission, the true DRG, currently determined only at discharge, is unknown. We approach the problem of early DRG determination in three stages: (1) test how much a Naive Bayes classifier can improve classification accuracy as compared to a hospital's current approach; (2) develop a statistical program that makes admission and scheduling decisions based on the patients' clincial pathways and scarce hospital resources; and (3) feed the DRG as classified by the Naive Bayes classifier and the hospitals' baseline approach into the model (which we evaluate in simulation). Our results reveal that the DRG grouper performs poorly in classifying the DRG correctly before admission while the Naive Bayes approach substantially improves the classification task. The results from the connection of the classification method with the mathematical program also reveal that resource allocation decisions can be more effective and efficient with the hybrid approach. PMID- 26262063 TI - An eHealth Approach to Reporting Allergic Reactions to Food and Closing the Knowledge Gap. AB - There is an important knowledge gap in food allergy management in understanding the factors that determine allergic reactions to food, in gathering objective reports of reactions in real time, and in accessing patients' reaction-histories during consultations. We investigate how eHealth methods can close this knowledge gap. We report experiences with an online tool for reporting allergic reactions that we have developed as a web application. This application has been successfully validated by participants from Ireland and the UK, and is currently being used in a pilot where participants report allergic reactions in near-real time. PMID- 26262064 TI - PancreApp: An Innovative Approach to Computational Individualization of Nutritional Therapy in Chronic Gastrointestinal Disorders. AB - Medical nutrition therapy has a pivotal role in the management of chronic gastrointestinal disorders, like chronic pancreatitis, inflammatory bowel diseases (Lesniowski-Crohn's disease and ulcerative colitis) or irritable bowel syndrome. The aim of this study is to develop, deploy and evaluate an interactive application for Windows and Android operating systems, which could serve as a digital diet diary and as an analysis and a prediction tool both for the patient and the doctor. The software is gathering details about patients' diet and associated fettle in order to estimate fettle change after future meals, specifically for an individual patient. In this paper we have described the process of idea development and application design, feasibility assessment using a phone survey, a preliminary evaluation on 6 healthy individuals and early results of a clinical trial, which is still an ongoing study. Results suggest that applied approximative approach (Shepard's method of 6-dimensional metric interpolation) has a potential to predict the fettle accurately; as shown in leave-one-out cross-validation (LOOCV). PMID- 26262065 TI - An Intelligent Ecosystem for Providing Support in Prehospital Trauma Care in Cuenca, Ecuador. AB - According to facts given by the World Health Organization, one in ten deaths worldwide is due to an external cause of injury. In the field of pre-hospital trauma care, adequate and timely treatment in the golden period can impact the survival of a patient. The aim of this paper is to show the design of a complete ecosystem proposed to support the evaluation and treatment of trauma victims, using standard tools and vocabulary such as OpenEHR, as well as mobile systems and expert systems to support decision-making. Preliminary results of the developed applications are presented, as well as trauma-related data from the city of Cuenca, Ecuador. PMID- 26262066 TI - Quantifying the Activities of Self-quantifiers: Management of Data, Time and Health. AB - Current self-quantification systems (SQS) are limited in their ability to support the acquisition of health-related information essential for individuals to make informed decisions based on their health status. They do not offer services such as data handling and data aggregation in a single place, and using multiple types of tools for this purpose complicates data and health self-management for self quantifiers. An online survey was used to elicit information from self quantifiers about the methods they used to undertake key activities related to health self-management. This paper provides empirical evidence about self quantifiers' time spent using different data collection, data handling, data analysis, and data sharing tools and draws implications for health self management activities. PMID- 26262067 TI - Mobile Usability Testing in Healthcare: Methodological Approaches. AB - The use of mobile devices and healthcare applications is increasing exponentially worldwide. This has lead to the need for the healthcare industry to develop a better understanding of the impact of the usability of mobile software and hardware upon consumer and health professional adoption and use of these technologies. There are many methodological approaches that can be employed in conducting usability evaluation of mobile technologies. More obtrusive approaches to collecting study data may lead to changes in study participant behaviour, leading to study results that are less consistent with how the technologies will be used in the real-world. Alternatively, less obstrusive methods used in evaluating the usability of mobile software and hardware in-situ and laboratory settings can lead to less detailed information being collected about how an individual interacts with both the software and hardware. In this paper we review and discuss several innovative mobile usability evaluation methods on a contiuum from least to most obtrusive and their effects on the quality of the usability data collected. The strengths and limitations of methods are also discussed. PMID- 26262068 TI - Making an APPropriate Care Program for Indigenous Cardiac Disease: Customization of an Existing Cardiac Rehabilitation Program. AB - Cardiovascular disease is a major health problem for all Australians and is the leading cause of death in Aboriginal and Torres Strait Islanders. In 2010, more then 50% of all heart attack deaths were due to repeated events. Cardiac rehabilitation programs have been proven to be effective in preventing the recurrence of cardiac events and readmission to hospitals. There are however, many barriers to the use of these programs. To address these barriers, CSIRO developed an IT enabled cardiac rehabilitation program delivered by mobile phone through a smartphone app and succesfully trialed it in an urban general population. If these results can be replicated in Indigenous populations, the program has the potential to significantly improve life expectancy and help close the gap in health outcomes. The challenge described in this paper is customizing the existing cardiac health program to make it culturally relevant and suitable for Indigenous Australians living in urban and remote communities. PMID- 26262069 TI - A Serious Game for Upper Limb Stroke Rehabilitation Using Biofeedback and Mirror Neurons Based Training. AB - Upper limb stroke rehabilitation requires early, intensive and repetitive practice to be effective. Consequently, it is often difficult to keep patients committed to their rehabilitation regimen. In addition to direct measures of rehabilitation achievable through targeted assessments, other factors can indirectly lead to rehabilitation. Current levels of integration between commodity graphics software, hardware, and body-tracking devices have provided a reliable tool to build what are referred to as serious games, focusing on the rehabilitation paradigm. More specifically, serious games can captivate and engage players for a specific purpose such as developing new knowledge or skills. This paper discusses a serious game application with a focus on upper limb rehabilitation in patients with hemiplegia or hemiparesis. The game makes use of biofeedback and mirror-neurons to enhance the patient's engagement. Results from the application of a quantitative self-report instrument to assess in-game engagement suggest that the serious game is a viable instructional approach rather than an entertaining novelty and, furthermore, demonstrates the future potential for dual action therapy-focused games. PMID- 26262070 TI - Usability and Safety of Software Medical Devices: Need for Multidisciplinary Expertise to Apply the IEC 62366: 2007. AB - Software medical devices must now comply with the "ergonomics" essential requirement of the Medical Device Directive. However, the usability standard aiming to guide the manufacturers is very difficult to understand and apply. Relying on a triangulation of methods, this study aims to highlight the need to combine various expertises to be able to grasp the standard. To identify the areas of expertise on which the usability standard relies, an analytical review of this document was performed as well as an analysis of a discussion forum dedicated to it and an analysis of a case study of its application for CE marking. The results show that the IEC 62366 is a usability standard structured as a risk management one. It obviously requires Human Factors/Ergonomics expertise to be able to correctly identify and prevent risks of use errors, but it also requires risk management expertise to be able to grasp the issues of the risk analysis and master the related methods. PMID- 26262071 TI - Evidence-based Heuristics for Evaluating Demands on eHealth Literacy and Usability in a Mobile Consumer Health Application. AB - Heuristic evaluations have proven to be valuable for identifying usability issues in systems. Commonly used sets of heuritics exist; however, they may not always be the most suitable, given the specific goal of the analysis. One such example is seeking to evaluate the demands on eHealth literacy and usability of consumer health information systems. In this study, eight essential heuristics and three optional heuristics subsumed from the evidence on eHealth/health literacy and usability were tested for their utility in assessing a mobile blood pressure tracking application (app). This evaluation revealed a variety of ways the design of the app could both benefit and impede users with limited eHealth literacy. This study demonstrated the utility of a low-cost, single evaluation approach for identifying both eHealth literacy and usability issues based on existing evidence in the literature. PMID- 26262072 TI - Evaluating the Impact of Player Experience in the Design of a Serious Game for Upper Extremity Stroke Rehabilitation. AB - Video games have become a major entertainment industry and one of the most popular leisure forms, ranging from laboratory experiments to a mainstream cultural medium. Indeed, current games are multimodal and multidimensional products, relying on sophisticated features including not only a narrative-driven story but also impressive graphics and detailed settings. All of these elements helped to create a seamless and appealing product that have resulted in a growing number of players and in the number of game genres. Although video games have been used in education, simulation, and training, another application that exploits serious gaming is the exploration of player experience in the context of game research. Recent advances in the natural user interfaces and player experience have brought new perspectives on the in-game assessment of serious games. This paper evaluates the impact of player experience in the design of a serious game for upper extremity stroke rehabilitation. The game combines biofeedback and mirror neurons both in single and multiplayer mode. Results have shown that the game is a feasible solution to integrate serious games into the physical therapy routine. PMID- 26262073 TI - User-Centered Design of Health Care Software Development: Towards a Cultural Change. AB - Health care software gets better user efficiency, efficacy and satisfaction when the software is designed with their users' needs taken into account. However, it is not trivial to change the practice of software development to adopt user centered design. In order to produce this change in the Health Informatics Department of the Hospital Italiano de Buenos Aires, a plan was devised and implemented. The article presents the steps of the plan, shows how the steps were carried on, and reflects on the lessons learned through the process. PMID- 26262074 TI - Online Continuing Medical Education for the Latin American Nephrology Community. AB - A continuing medical education (CME) course was implemented for Latin American nephrologists in 2013. The topic was Immunopathology in native and transplanted kidneys. The course was given in Spanish and Portuguese. The activities included a distance education seven-week asynchronous online modality with multiple educational strategies. Thirty hours of study workload were estimated to complete the course. Four hundred and ninety-eight physicians coming from 18 countries registered for the course; 442 of them participated in it. Of those who participated, 51% received a certificate of completion and 29% a certificate of participation. Sixty-five percent of registrants participated in the case discussions. Eighty-six percent were very satisfied and 13% were satisfied. Lack of time to devote to the course was the main limitation expressed (62%), while Internet access or difficulties in the use of technology were considered by only 12 and 6% of participants, respectively. There was a significant increase in knowledge between before and after the course; the average grade increased from 64 to 83%. In conclusion, technology-enabled education demonstrated potential to become an instrument for Latin American nephrologists. PMID- 26262075 TI - Danish Citizens and General Practitioners' Use of ICT for their Mutual Communication. AB - This paper reports on selected findings from a Danish national survey of citizens' perception and use of information and communication technology (ICT) for their health care [1]. Focus is on citizens' use of ICT and on communication with their General Practitioner (GP). It also focuses on citizens' experience of their GPs' ICT use and no use during medical consultations. The responsibility for medical service in Denmark is to a large extent handed over to the primary sector where the GP is the gatekeeper. Our data display that 65% of the adult citizens or their relatives have been using ICT to communicate with their GP. Twenty-two percent have experienced their GP use a computer screen to actively show them something while they have a consultation. Further, our data supports the assumption that the higher the education people have, the more likely they are to use ICT for their health care. The understanding of the use of ICT in communication with the GP is central to monitoring and developing an ICT that supports all citizens and considers new ways in which to enhance quality of care. PMID- 26262076 TI - The Online Availability of Multilingual Health Promotion Materials Produced by Local Health Departments: an Information Assessment. AB - OBJECTIVES: Local Health Departments (LHDs) are a key source of health promotion information. For ethnically and culturally diverse communities, it becomes important to provide minorities with language appropriate health information. This project sought to assess the availability of multilingual health promotion materials on LHD websites in Washington State (WA), USA. METHODS: We performed a cross-sectional study of all 34 LHD websites in WA. We collected and classified health promotion documents available to the public, specifically, whether translated versions were available. We also assessed the extent of document sharing between LHDs. RESULTS: We identified 1,624 documents across 34 LHDs. Topics most frequently covered were communicable diseases and emergency preparedness. Fewer than 10% of documents were available in non-English languages. We found little evidence of document sharing between LHDs; only 5% of all documents were shared between LHDs. CONCLUSIONS: WA LHDs provide a variety of health promotion materials for the public, but few multilingual materials are available online. New technologies for facilitating document sharing and machine translation may improve the present landscape. PMID- 26262077 TI - Serious Games: A Concise Overview on What They Are and Their Potential Applications to Healthcare. AB - Younger generations are extensive users of digital devices; these technologies have always existed and have always been a part of their lives. Video games are a big part of their digital experience. User-centered design is an approach to designing systems informed by scientific knowledge of how people think, act, and coordinate to accomplish their goals. There is an emerging field of intervention research looking into using these techniques to produce video games that can be applied to healthcare. Games with the purpose of improving an individual's knowledge, skills, or attitudes in the "real" world are called "Serious Games". Before doctors and patients can consider using Serious Games as a useful solution for a health care-related problem, it is important that they first are aware of them, have a basic understanding of what they are, and what, if any, claims on their effectiveness exist. In order to bridge that gap, we have produced this concise overview to introduce physicians to the subject at hand. PMID- 26262078 TI - Living with Lung Cancer--Patients' Experiences as Input to eHealth Service Design. AB - The objective of the study is to describe the lung cancer care process as experienced by patients, as well as to perform a qualitative analysis of problems they encounter throughout the patient journey. A user-centered design approach was used and data collected through two focus group meetings with patients. We present the results in the form of a patient journey model, descriptions of problems related to the journey as expressed by patients and proposed eHealth services discussed by patients in the focus groups. The results indicate that not only is the patient journey fragmented and different for each patient going through it depending upon their specific type of lung cancer and treatment options, but their experiences are also highly individual and dependent on their personal needs and interpretations of the process. Designing eHealth to improve the patient journey will therefore require flexibility and adaptability to the individual's needs. PMID- 26262079 TI - Applying a Geospatial Visualization Based on USSD Messages to Real Time Identification of Epidemiological Risk Areas in Developing Countries: A Case of Study of Paraguay. AB - The identification of epidemiological risk areas is one of the major problems in public health. Information management strategies are needed to facilitate prevention and control of disease in the affected areas. This paper presents a model to optimize geographical data collection of suspected or confirmed disease occurrences using the Unstructured Supplementary Service Data (USSD) mobile technology, considering its wide adoption even in developing countries such as Paraguay. A Geographic Information System (GIS) is proposed for visualizing potential epidemiological risk areas in real time, that aims to support decision making and to implement prevention or contingency programs for public health. PMID- 26262080 TI - Using Publicly Available Data to Characterize Consumers Use of Email to Communicate with Healthcare Providers. AB - The use of patient focused technology has been proclaimed as a means to improve patient satisfaction and improve care outcomes. The Center for Medicaid/Medicare Services, through its EHR Incentive Program, has required eligible hospitals and professionals to send and receive secure messages from patients in order to receive financial incentives and avoid reimbursement penalties. Secure messaging between providers and patients has the potential to improve communication and care outcomes. The purpose of this study was to use National Health Interview Series (NHIS) data to identify the patient characteristics associated with communicating with healthcare providers via email. Individual patient characteristics were analyzed to determine the likelihood of emailing healthcare providers. The use of email for this purpose is associated with educational attainment, having a usual place of receiving healthcare, income, and geography. Publicly available data such as the NHIS may be used to better understand trends in adoption and use of consumer health information technologies. PMID- 26262081 TI - Health Information Technology Evaluation Framework (HITREF) Comprehensiveness as Assessed in Electronic Point-of-Care Documentation Systems Evaluations. AB - We assessed the Health Information Technology (HIT) Reference-based Evaluation Framework (HITREF) comprehensiveness in two HIT evaluations in settings different from that in which the HITREF was developed. Clinician satisfaction themes that emerged from clinician interviews in the home care and the hospital studies were compared to the framework components. Across both studies, respondents commented on 12 of the 20 HITREF components within 5 of the 6 HITREF concepts. No new components emerged that were missing from the HITREF providing evidence that the HITREF is a comprehensive framework. HITREF use in a range of HIT evaluations by researchers new to the HITREF demonstrates that it can be used as intended. Therefore, we continue to recommend the HITREF as a comprehensive, research-based HIT evaluation framework to increase the capacity of informatics evaluators' use of best practice and evidence-based practice to support the credibility of their findings for fulfilling the purpose of program evaluation. PMID- 26262082 TI - Patient Outcomes as Transformative Mechanisms to Bring Health Information Technology Industry and Research Informatics Closer Together. AB - Despite the fast pace of recent innovation within the health information technology and research informatics domains, there remains a large gap between research and academia, while interest in translating research innovations into implementations in the patient care settings is lacking. This is due to absence of common outcomes and performance measurement targets, with health information technology industry employing financial and operational measures and academia focusing on patient outcome concerns. The paper introduces methodology for and roadmap to introduction of common objectives as a way to encourage better collaboration between industry and academia using patient outcomes as a composite measure of demonstrated success from health information systems investments. Along the way, the concept of economics of health informatics, or "infonomics," is introduced to define a new way of mapping future technology investments in accordance with projected clinical impact. PMID- 26262084 TI - The Case for Conceptual and Computable Cross-Fertilization Between Audit and Feedback and Clinical Decision Support. AB - Many patients do not receive care consistent with best practice. Health informatics interventions often attempt to address this problem by comparing care provided to patients (e.g., from electronic health record data) to quality standards (e.g., described in clinical guidelines) and feeding this information back to clinicians. Traditionally these interventions are delivered at the patient-level as computerized clinical decision support (CDS) or at the population level as audit and feedback (A&F). Both CDS and A&F can improve care for patients but are variably effective; the challenge is to understand how the efficacy can be maximized. Although CDS and A&F are traditionally considered separate approaches, we argue that the systems share common mechanisms, and efficacy may be improved by cross-fertilizing relevant features and concepts. We draw on the Health Informatics and Implementation Science literature to argue that common mechanisms include functions typically associated with the other system, in addition to other features that may prove fruitful for further research. PMID- 26262083 TI - Domain Analysis of Integrated Data to Reduce Cost Associated with Liver Disease. AB - Liver cancer, the fifth most common cancer and second leading cause of cancer related death among men worldwide, is plagued by not only lack of clinical research, but informatics tools for early detection. Consequently, it presents a major health and cost burden. Among the different types of liver cancer, hepatocellular carcinoma (HCC) is the most common and deadly form, arising from underlying liver disease. Current models for predicting risk of HCC and liver disease are limited to clinical data. A domain analysis of existing research related to screening for HCC and liver disease suggests that metabolic syndrome (MetS) may present oppportunites to detect early signs of liver disease. The purpose of this paper is to (i) provide a domain analysis of the relationship between HCC, liver disease, and metabolic syndrome, (ii) a review of the current disparate sources of data available for MetS diagnosis, and (iii) recommend informatics solutions for the diagnosis of MetS from available administrative (Biometrics, PHA, claims) and laboratory data, towards early prediction of liver disease. Our domain analysis and recommendations incorporate best practices to make meaningful use of available data with the goal of reducing cost associated with liver disease. PMID- 26262085 TI - Inside the Black Box of Audit and Feedback: a Laboratory Study to Explore Determinants of Improvement Target Selection by Healthcare Professionals in Cardiac Rehabilitation. AB - Audit and feedback (A&F) is widely used to aid healthcare professionals in improving clinical performance, but there is little understanding of the underlying mechanism that determines its effectiveness. The aim of this paper is to investigate the process by which healthcare professionals select indicators as improvement targets based on A&F. We performed a laboratory study among 41 healthcare professionals in the context of a web-based A&F intervention designed to improve the quality of cardiac rehabilitation care in the Netherlands. Feedback was provided on eighteen quality indicators, including a score and a colour (representing a recommendation for selection (red and yellow) or non selection (green)). Indicators with more room for improvement were more likely to be selected, although this varied substantially between participants. In more than a quarter of the cases, participants did not select indicators with obvious room for improvement (yellow or red colour), or selected indicators without apparent room for improvement (green colour). We conclude that personal preferences and beliefs concerning quality and performance targets may dilute the efficiency of A&F. PMID- 26262086 TI - Using Patient Journey Modelling to Visualise the Impact of Policy Change on Patient Flow in Community Care. AB - Health policy plays a crucial role in community care, particularly within care programs such as ComPacks. ComPacks is a short-term care program administered by New South Wales (NSW) department of health which runs for up to 6-weeks and its goal is to prevent or minimise hospital readmission. Compliance to the ComPacks health policies is required in order to gain financial support from overnment bodies, however when the Government makes changes to service policies, this may potentially cause ripple effects to the workflow of the service and increase pressures on care providers, which in turn may affect the patient. Utilising a multi-layer visualisation tool can help identify whether changes made to policy are impacting patient flow in a positive or negative way. This research study investigates the use of an emerging patient journey modelling technique to better understand service design in a community care setting, whilst also determining the impact of State-level policy interventions. PMID- 26262087 TI - Challenges and Hurdles of eHealth Implementation in Developing Countries. AB - Health informatics has the potential to improve the security and quality of patient care, but its impact has varied between developed and developing countries. Related to this, the objective of this study is to identify the challenges and hurdles to improve eHealth in developing countries. We surveyed experts to discover their opinions about five general questions: economic support by Government for eHealth, Government education or training projects in the field, issues related to cultural or educational problems for the implementation of eHealth, policies in terminology or messaging standards and eHealth status policies for long periods. The respondents answered affirmatively in these proportions: 1. Economic support policies 58%, 2. Training policies 25%, 3. Cultural and educational problems 95%, 4. Standards policies, 38%, 5. Policies for long periods, 50% CONCLUSION: Our survey has shown that the important problems that need to be addressed in order to implement e-Health in developing countries are firstly, cultural and educational, secondly, economic resources and thirdly policies for long periods. PMID- 26262088 TI - On the Development of a Hospital-Patient Web-Based Communication Tool: A Case Study From Norway. AB - Surgery cancellations are undesirable in hospital settings as they increase costs, reduce productivity and efficiency, and directly affect the patient. The problem of elective surgery cancellations in a North Norwegian University Hospital is addressed. Based on a three-step methodology conducted at the hospital, the preoperative planning process was modeled taking into consideration the narratives from different health professions. From the analysis of the generated process models, it is concluded that in order to develop a useful patient centered web-based communication tool, it is necessary to fully understand how hospitals plan and organize surgeries today. Moreover, process reengineering is required to generate a standard process that can serve as a tool for health ICT designers to define the requirements for a robust and useful system. PMID- 26262089 TI - Barriers and facilitators to the introduction of digital pathology for diagnostic work. AB - Cellular pathologists are doctors who diagnose disease by using a microscope to examine glass slides containing thin sections of human tissue. These slides can be digitised and viewed on a computer, promising benefits in both efficiency and safety. Despite this, uptake of digital pathology for diagnostic work has been slow, with use largely restricted to second opinions, education, and external quality assessment schemes. To understand the barriers and facilitators to the introduction of digital pathology, we have undertaken an interview study with nine consultant pathologists. Interviewees were able to identify a range of potential benefits of digital pathology, with a particular emphasis on easier access to slides. Amongst the barriers to use, a key concern was lack of familiarity, not only in terms of becoming familiar with the technology but learning how to adjust their diagnostic skills to this new medium. The findings emphasise the need to ensure adequate training and support and the potential benefit of allowing parallel use of glass slides and digital while pathologists are on the learning curve. PMID- 26262090 TI - Big Data Clinical Research: Validity, Ethics, and Regulation. AB - Electronic Health Records (EHR) promise improvement for patient care and also offer great value for biomedical research including clinical, public health, and health services research. Unfortunately, the full potential of EHR big data research has remained largely unrealized. The purpose of this study was to identify rate limiting factors, and develop recommendations to better balance unrestricted extramural EHR access with legitimate safeguarding of EHR data in retrospective research. By exploring primary, secondary, and tertiary sources, this review identifies external constraints and provides a comparative analysis of social influencers in retrospective EHR-based research. Results indicate that EHRs have the advantage of reflecting the reality of patient care but also show a frequency of between 4.3-86% of incomplete and inaccurate data in various fields. The rapid spread of alternative analytics for health data challenges traditional interpretations of confidentiality protections. A confusing multiplicity of controls creates barriers to big data EHR research. More research on the use of EHR big data is likely to improve accuracy and validity. Information governance and research approval processes should be simplified. Comprehensive regulatory policies that do not exclusively cover health care entities, are needed. Finally, new computing safeguards are needed to address public concerns, like research access only to aggregate data and not to individually identifiable information. PMID- 26262091 TI - Streaming Physiological Data: General Public Perceptions of Secondary Use and Application to Research in Neonatal Intensive Care. AB - High speed physiological data represents one of the most untapped resources in healthcare today and is a form of Big Data. Physiological data is captured and displayed on a wide range of devices in healthcare environments. Frequently this data is transitory and lost once initially displayed. Researchers wish to store and analyze these datasets, however, there is little evidence of any engagement with citizens regarding their perceptions of physiological data capture for secondary use. This paper presents the findings of a self-administered household survey (n=165, response rate = 34%) that investigated Australian and Canadian citizens' perceptions of such physiological data capture and re-use. Results indicate general public support for the secondary use of physiological streaming data. Discussion considers the potential application of such data in neonatal intensive care contexts in relation to our Artemis research. Consideration of the perceptions of secondary use of the streaming data as early as possible will assist in building appropriate use models, with a focus on parents in the neonatal context. PMID- 26262092 TI - Driving the Profession of Health Informatics: The Australasian College of Health Informatics. AB - Across the world, bodies representing health informatics or promoting health informatics are either societies of common interest or universities with health informatics courses/departments. Professional colleges in Health Informatics (similar to the idea of professional colleges in other health fields) are few and far between. The Australasian College of Health Informatics has been in existence since 2001, and has an increasing membership of nearly 100 fellows and members, acting as a national focal point for the promotion of Health Informatics in Australasia. Describing the activities of the college, this article demonstrates a need for increasing professionalization of Health informatics beyond the current structures. PMID- 26262093 TI - Person-Specific Standardized Vulnerability Assessment in Health and Social Care. AB - We describe an integrated person-specific standardized vulnerability assessment model designed to facilitate patient management in health and social care. Such a system is not meant to replace existing health and social assessment models but rather to complement them by providing a holistic picture of the vulnerabilities faced by a given patient. In fact, it should be seen as a screening tool for health and social care workers. One key aspect of the modeling framework is the ability to provide personalized yet standardized multi-dimensional assessments of risk based on incomplete information about the patient status, as is the case in screening situations. Specifically, we integrate a Markov chain model describing the evolution of patients in and out of vulnerable states over time with a Bayesian network that serves to customize the dynamic model. We present an application in the context of elder care. PMID- 26262094 TI - Trust, Perceived Risk, Perceived Ease of Use and Perceived Usefulness as Factors Related to mHealth Technology Use. AB - Mobile technology use is nearly ubiquitous which affords the opportunity for using these technologies for modifying health related behaviors. At the same time, use of mobile health (mHealth) technology raises privacy and security concerns of consumers. The goal of this analysis was to understand the perceived ease of use, usefulness, risk and trust that contribute to behavioral intention to use a mobile application for meeting the healthcare needs of persons living with HIV (PLWH). To understand these issues, we conducted focus group sessions with 50 persons living with HIV and 30 HIV healthcare providers. We used the e commerce acceptance model to analyze our focus group data. Findings from the study demonstrated the need for mHealth to be perceived as useful, easy to use, with little perceived risk accompanied by a measure of trust in the creators of the technology. Findings from this work can inform future work on patients and providers' perceptions of risk, trust, ease of use and usefulness of mHealth technology. PMID- 26262095 TI - Electronic Health Record System Contingency Plan Coordination: A Strategy for Continuity of Care Considering Users' Needs. AB - Electronic Health Record system downtimes may have a great impact on patient care continuity. This paper describes the analysis and actions taken to redesign the Contingency Plan Procedure for the Electronic Health Record System of Hospital Italiano de Buenos Aires. After conducting a thorough analysis of the data gathered at post-contingency meetings, weaknesses were identified in the procedure; thus, strategic actions were recommended to redesign the Contingency Plan to secure an effective communications channel, as well as a formal structure for functions that may support the decision-making process. The main actions were: 1) to incorporate the IT Contingencies Committee (Plan management); 2) to incorporate the Coordinator (general supervision of the procedure); and 3) to redefine the role of the Clinical Informatics Resident, who will be responsible for managing communication between the technical team and Electronic Health Record users. As users need the information for continuity of care, key users evaluated the impact of the new strategy with an adapted survey. PMID- 26262096 TI - Flexibility First, Then Standardize: A Strategy for Growing Inter-Departmental Systems. AB - Any attempt to use IT to standardize work practices faces the challenge of finding a balance between standardization and flexibility. In implementing electronic whiteboards with the goal of standardizing inter-departmental practices, a hospital in Denmark chose to follow the strategy of "flexibility first, then standardization." To improve the local grounding of the system, they first focused on flexibility by configuring the whiteboards to support intra departmental practices. Subsequently, they focused on standardization by using the white-boards to negotiate standardization of inter-departmental practices. This paper investigates the chosen strategy and finds: that super users on many wards managed to configure the whiteboard to support intra-departmental practices; that initiatives to standardize inter-departmental practices improved coordination of certain processes; and that the chosen strategy posed a challenge for finding the right time and manner to shift the balance from flexibility to standardization. PMID- 26262097 TI - Human Factors Predicting Failure and Success in Hospital Information System Implementations in Sub-Saharan Africa. AB - From 2007 through 2014, the authors participated in the implementation of open source hospital information systems (HIS) in 19 hospitals in Rwanda, Burundi, DR Congo, Congo-Brazzaville, Gabon, and Mali. Most of these implementations were successful, but some failed. At the end of a seven-year implementation effort, a number of risk factors, facilitators, and pragmatic approaches related to the deployment of HIS in Sub-Saharan health facilities have been identified. Many of the problems encountered during the HIS implementation process were not related to technical issues but human, cultural, and environmental factors. This study retrospectively evaluates the predictive value of 14 project failure factors and 15 success factors in HIS implementation in the Sub-Saharan region. Nine of the failure factors were strongly correlated with project failure, three were moderately correlated, and one weakly correlated. Regression analysis also confirms that eight factors were strongly correlated with project success, four moderately correlated, and two weakly correlated. The study results may help estimate the expedience of future HIS projects. PMID- 26262098 TI - Implementing a National Scottish Digital Health & Wellbeing Service at Scale: A Qualitative Study of Stakeholders' Views. AB - Digital technologies are being used as part of international efforts to revolutionize healthcare in order to meet increasing demands such as the rising burden of chronic disease and ageing populations. In Scotland there is a government push towards a national service (Living It Up) as a single point of reference where citizens can access information, products and services to support their health and wellbeing. The aim of the study is to examine implementation issues including the challenges or facilitators which can help to sustain this intervention. We gathered data in three ways: a) participant observation to gain an understanding of LiU (N=16); b) in-depth interviews (N=21) with stakeholders involved in the process; and c) analysis of documentary evidence about the progress of the implementation (N=45). Barriers included the need to "work at risk" due to delays in financing, inadequate infrastructure and skill-set deficiencies, whilst facilitators included trusted relationships, champions and a push towards normalisation. The findings suggest that a Scottish ehealth service is achievable but identifies key considerations for future large scale initiatives. PMID- 26262099 TI - Evaluating a Proof-of-Concept Approach of the German Health Telematics Infrastructure in the Context of Discharge Management. AB - Although national eHealth strategies have existed now for more than a decade in many countries, they have been implemented with varying success. In Germany, the eHealth strategy so far has resulted in a roll out of electronic health cards for all citizens in the statutory health insurance, but in no clinically meaningful IT-applications. The aim of this study was to test the technical and organisation feasibility, usability, and utility of an eDischarge application embedded into a laboratory Health Telematics Infrastructure (TI). The tests embraced the exchange of eDischarge summaries based on the multiprofessional HL7 eNursing Summary standard between a municipal hospital and a nursing home. All in all, 36 transmissions of electronic discharge documents took place. They demonstrated the technical-organisation feasibility and resulted in moderate usability ratings. A comparison between eDischarge and paper-based summaries hinted at higher ratings of utility and information completeness for eDischarges. Despite problems with handling the electronic health card, the proof-of-concept for the first clinically meaningful IT-application in the German Health TI could be regarded as successful. PMID- 26262100 TI - Monitoring Telemedicine Implementation in Denmark. AB - According to the literature, Denmark has a leading position in the dissemination and use of health informatics. However, there is a lack of systematically collected and documented experience of telemedicine solutions in Denmark. This evidence is being established with a new project, which maps out all telemedicine initiatives in Denmark. Data on all the initiatives is collected in a single database and some of the data is analyzed in this paper. It is shown that there are a very large number of telemedicine initiatives in Denmark and that the elements from the national strategy for telemedicine are clearly visible in the telemedicine map. The very large number of projects could, however, also indicate a lack of national coordination of initiatives and a need for evaluation activities to systematically collect and communicate the learning outcomes from all the new projects. PMID- 26262101 TI - Clinical Informatics Board Specialty Certification for Physicians: A Global View. AB - Clinical informatics workforce development is a high priority for medicine. Professional board certification for physicians is an important tool to demonstrating excellence. The recent recognition of clinical informatics as a subspecialty board in the U.S. has generated interest and excitement among the U.S. informatics community. To determine the extent of similar programs in countries around the world, we performed literature searches with relevant keywords and internet searches of websites of informatics societies around the world for mentions or descriptions of certifications and reviewed publicly available sources. The U.S. certification was prominent in the recent published literature. Germany and Belgium have long-standing certifications with South Korea and Sri Lanka considering similar programs. This is the first global view of clinical informatics board certification for physicians. Training and certification for non-physician informatics professionals in allied areas are widespread. Official recognition and certification for physicians and all informatics professionals represents a key component of capacity building and a means of addressing the shortage of a skilled informatics workforce. Wider adoption of certification programs may further attracting talent and accelerate growth of the field. PMID- 26262102 TI - A Pilot Study of Computer-Based Simulation Training for Enhancing Family Medicine Residents' Competence in Computerized Settings. AB - We previously developed a prototype computer-based simulation to teach residents how to integrate better EMR use in the patient-physician interaction. To evaluate the prototype, we conducted usability tests with three non-clinician students, followed by a pilot study with 16 family medicine residents. The pilot study included pre- and post-test surveys of competencies and attitudes related to using the EMR in the consultation and the acceptability of the simulation, as well as 'think aloud' observations. After using the simulation prototypes, the mean scores for competencies and attitudes improved from 14.88/20 to 15.63/20 and from 22.25/30 to 23.13/30, respectively; however, only the difference for competencies was significant (paired t-test; t=-2.535, p=0.023). Mean scores for perceived usefulness and ease of use of the simulation were good (3.81 and 4.10 on a 5-point scale, respectively). Issues identified in usability testing include confusing interaction with some features, preferences for a more interactive representation of the EMR, and more options for shared decision making. In conclusion, computer-based simulation may be an effective and acceptable tool for teaching residents how to better use EMRs in clinical encounters. PMID- 26262103 TI - Mind the Gap: The Discrepancies between Patient Self-Reported Quality of Life and Medical Staff-Estimated Quality of Life. AB - Information on patient quality of life (QOL) is essential to many clinical decisions. Therefore, studies that aim to extract QOL information from patient narratives are increasingly drawing attention. Also, several studies have noted that web services for patients, such as patient social networking services, may represent promising resources for QOL research. However, it is still unclear whether patient narrative text contains corresponding amounts of QOL information as self-reported QOL. This study investigates if medical staff can accurately estimate patient QOL from only patient narrative texts. We analyzed (1) QOL of cancer patients estimated by medical staff from patient autobiographical texts and (2) self-reported QOL scores of cancer patients. We compared patients from the following 3 disease groups: (1) gastrointestinal cancer, (2) breast cancer, and (3) lymphoma. The SF-36v2TM Health Survey was used to measure patient QOL in both materials, and the QOLs were compared. We found significant differences between self-reported QOL and estimated QOL in breast cancer patients and lymphoma patients, but not in gastrointestinal cancer patients. In particular, the medical staff tended to underestimate physical QOL scores. Medical staff may underestimate several aspects of QOL scores. On the basis of these results, we may be able to achieve more precise QOL estimation from patient narratives. PMID- 26262104 TI - Identifying Effective Approaches for Dissemination of Clinical Evidence- Correlation Analyses on Promotional Activities and Usage of a Guideline-Driven Interactive Case Simulation Tool in a Statewide HIV-HCV-STD Clinical Education Program. AB - Dissemination of the latest clinical evidence to community-based healthcare providers is a critical step to translate biomedical knowledge into clinical practice. We performed a study to analyze the correlations between the promotional activities and the usage of a guideline-driven interactive case simulation tool (ICST) for insomnia screening and treatment in a statewide HIV HCV-STD clinical education program. For this purpose, we tracked users' interactions with the ICST and the sending of promotional email newsletters during a study period of 44 weeks. Results showed that promotional activities were strongly correlated with the number of audience as well as the intensity of use of the target resource. The strength of correlation varied in specific use contexts. Strong correlations were found between the sending of email newsletters and the intensity of resource use by promotion recipients, by new users, and through the most convenient access channel associated with the promotion. Selection of approaches for resource dissemination should consider the potentials and limitations of use contexts to make them more effective. PMID- 26262105 TI - Building Comprehensive and Sustainable Health Informatics Institutions in Developing Countries: Moi University Experience. AB - Current approaches for capacity building in Health Informatics (HI) in developing countries mostly focus on training, and often rely on support from foreign entities. In this paper, we describe a comprehensive and multidimensional capacity-building framework by Lansang & Dennis, and its application for HI capacity building as implemented in a higher-education institution in Kenya. This framework incorporates training, learning-by-doing, partnerships, and centers of excellence. At Moi University (Kenya), the training dimensions include an accredited Masters in HI Program, PhD in HI, and HI short courses. Learning-by doing occurs through work within MOH facilities at the AMPATH care and treatment program serving 3 million people. Moi University has formed strategic HI partnerships with Regenstrief Institute, Inc. (USA), University of Bergen (Norway), and Makerere University (Uganda), among others. The University has also created an Institute of Biomedical Informatics to serve as an HI Center of Excellence in the region. This Institute has divisions in Training, Research, Service and Administration. The HI capacity-building approach by Moi provides a model for adoption by other institutions in resource-limited settings. PMID- 26262106 TI - Health Informatics: Developing a Masters Programme in Rwanda based on the IMIA Educational Recommendations and the IMIA Knowledge Base. AB - Since 2011, the Regional e-Health Center of Excellence in Rwanda (REHCE) has run an MSc in Health Informatics programme (MSc HI). A programme review was commissioned in February 2014 after 2 cohorts of students completed the post graduate certificate and diploma courses and most students had started preparatory activity for their master dissertation. The review developed a method for mapping course content on health informatics competences and knowledge units. Also the review identified and measured knowledge gaps and content redundancy. Using this method, we analyzed regulatory and programme documents combined with stakeholder interviews, and demonstrated that the existing MSc HI curriculum did not completely address the needs of the Rwandan health sector. Teaching strategies did not always match students' expectations. Based on a detailed Rwandan health informatics needs assessment, International Medical Informatics Association (IMIA)'s Recommendations on Education in Biomedical and Health Informatics and the IMIA Health Informatics Knowledge Base, a new curriculum was developed and provided a better competences match for the specifics of healthcare in the Central African region. The new approved curriculum will be implemented in the 2014/2015 academic year and options for regional extension of the programme to Eastern DRC (Bukavu) and Burundi (Bujumbura) are being investigated. PMID- 26262107 TI - Indexing Publicly Available Health Data with Medical Subject Headings (MeSH): An Evaluation of Term Coverage. AB - As part of the Open Government Initiative, the United States federal government published datasets to increase collaboration, transparency, consumer participation, and research, and are available online at HealthData.gov. Currently, HealthData.gov does not adequately support the accessibility goal of the Open Government Initiative due to issues of retrieving relevant data because of inadequately cataloguing and lack of indexing with a standardized terminology. Given the commonalities between the HealthData.gov and MEDLINE metadata, Medical Subject Headings (MeSH) may offer an indexing solution, but there needs to be a formal evaluation of the efficacy of MeSH for covering the dataset concepts. The purpose of this study was to determine if MeSH adequately covers the HealthData.gov concepts. The noun and noun phrases from the HealthData.gov metadata were extracted and mapped to MeSH using MetaMap. The frequency of no exact, partical and no matches with MeSH terms were determined. The results of this study revealed that about 70% of the HealthData.gov concepts partially or exactly matched MeSH terms. Therefore, MeSH may be a favorable terminology for indexing the HealthData.gov datasets. PMID- 26262108 TI - Recruit--An Ontology Based Information Retrieval System for Clinical Trials Recruitment. AB - Clinical trials are studies designed to assess whether a new intervention is better than the current alternatives. However, most of them fail to recruit participants on schedule. It is hard to use Electronic Health Record (EHR) data to find eligible patients, therefore studies rely on manual assessment, which is time consuming, inefficient and requires specialized training. In this work we describe the design and development of an information retrieval system with the objective of finding eligible patients for cancer trials. The Recruit system has been in use at A. C. Camargo Cancer Center since August/2014 and contains data from more than 500,000 patients and 9 databases. It uses ontologies to integrate data from several sources and represent medical knowledge, which helps enhance results. One can search both in structured data and inside free text reports. The preliminary quality assessments shows excellent recall rates. Recruit proved to be an useful tool for researchers and its modular design could be applied to other clinical conditions and hospitals. PMID- 26262109 TI - Assessing the Need of Discourse-Level Analysis in Identifying Evidence of Drug Disease Relations in Scientific Literature. AB - Relation extraction typically involves the extraction of relations between two or more entities occurring within a single or multiple sentences. In this study, we investigated the significance of extracting information from multiple sentences specifically in the context of drug-disease relation discovery. We used multiple resources such as Semantic Medline, a literature based resource, and Medline search (for filtering spurious results) and inferred 8,772 potential drug-disease pairs. Our analysis revealed that 6,450 (73.5%) of the 8,772 potential drug disease relations did not occur in a single sentence. Moreover, only 537 of the drug-disease pairs matched the curated gold standard in Comparative Toxicogenomics Database (CTD), a trusted resource for drug-disease relations. Among the 537, nearly 75% (407) of the drug-disease pairs occur in multiple sentences. Our analysis revealed that the drug-disease pairs inferred from Semantic Medline or retrieved from CTD could be extracted from multiple sentences in the literature. This highlights the significance of the need of discourse level analysis in extracting the relations from biomedical literature. PMID- 26262110 TI - InfoRoute: the CISMeF Context-specific Search Algorithm. AB - OBJECTIVE: The aim of this paper was to present a practical InfoRoute algorithm and applications developed by CISMeF to perform a contextual information retrieval across multiple medical websites in different health domains. METHODS: The algorithm was developed to treat multiple types of queries: natural, Boolean and advanced. The algorithm also generates multiple types of queries: Boolean query, PubMed query or Advanced query. Each query can be extended via an inter alignments relationship from UMLS and HeTOP portal. RESULTS: A web service and two web applications have been developed based on the InfoRoute algorithm to generate links-query across multiple websites, i.e.: "PubMed" or "ClinicalTrials.org". CONCLUSION: The InfoRoute algorithm is a useful tool to perform contextual information retrieval across multiple medical websites in both English and French. PMID- 26262111 TI - A Baseline Patient Model to Support Testing of Medical Cyber-Physical Systems. AB - Medical Cyber-Physical Systems (MCPS) are currently a trending topic of research. The main challenges are related to the integration and interoperability of connected medical devices, patient safety, physiologic closed-loop control, and the verification and validation of these systems. In this paper, we focus on patient safety and MCPS validation. We present a formal patient model to be used in health care systems validation without jeopardizing the patient's health. To determine the basic patient conditions, our model considers the four main vital signs: heart rate, respiratory rate, blood pressure and body temperature. To generate the vital signs we used regression models based on statistical analysis of a clinical database. Our solution should be used as a starting point for a behavioral patient model and adapted to specific clinical scenarios. We present the modeling process of the baseline patient model and show its evaluation. The conception process may be used to build different patient models. The results show the feasibility of the proposed model as an alternative to the immediate need for clinical trials to test these medical systems. PMID- 26262112 TI - Leveraging Electronic Tablets and a Readily Available Data Capture Platform to Assess Chronic Pain in Children: The PROBE system. AB - The Patient Risks Outcomes and Barriers Evaluation (PROBE) system is developed using a readily available data capture platform (REDCap) and iPads. PROBE performs complete and consistent assessment of pain at every patient visit in pediatric rheumatology practices of our very large healthcare system. Using evidence based clinical guidelines, it combines the following essential elements for care: 1) screening for behavioral risks for chronic pain such as anxiety, sleep deprivation, or painful conditions affecting a caregiver living in child's home, 2) capturing disease activity related measures and enabling 3) clinical decision support. In this demonstration project we describe PROBE and evaluate it for usability in practice. Using PROBE, we observed significant differences for behavioral risk factors in children with juvenile idiopathic arthritis in those who report chronic pain vs. not. PMID- 26262113 TI - Normalization of Phenotypic Data from a Clinical Data Warehouse: Case Study of Heterogeneous Blood Type Data with Surprising Results. AB - Clinical data warehouses often contain analogous data from disparate sources, resulting in heterogeneous formats and semantics. We have developed an approach that attempts to represent such phenotypic data in its most atomic form to facilitate aggregation. We illustrate this approach with human blood antigen typing (ABO-Rh) data drawn from the National Institutes of Health's Biomedical Translational Research Information System (BTRIS). In applying the method to actual patient data, we discovered a 2% incidence of changed blood types. We believe our approach can be applied to any institution's data to obtain comparable patient phenotypes. The actual discrepant blood type data will form the basis for a future study of the reasons for blood typing variation. PMID- 26262114 TI - Automatic Selection of Clinical Trials Based on A Semantic Web Approach. AB - Recruitment of patients in clinical trials is nowadays preoccupying, as the inclusion rate is particularly low. The main identified factors are the multiplicity of open clinical trials, the high number and complexity of eligibility criteria, and the additional workload that a systematic search of the clinical trials a patient could be enrolled in for a physician. The principal objective of the ASTEC project is to automate the prescreening phase during multidisciplinary meetings (MDM). This paper presents the evaluation of a computerized recruitment support systems (CRSS) based on semantic web approach. The evaluation of the system was based on data collected retrospectively from a 6 month period of MDM in Urology and on 4 clinical trials of prostate cancer. The classification performance of the ASTEC system had a precision of 21%, recall of 93%, and an error rate equal to 37%. Missing data was the main issue encountered. The system was designed to be both scalable to other clinical domains and usable during MDM process. PMID- 26262115 TI - Assessing the Collective Population Representativeness of Related Type 2 Diabetes Trials by Combining Public Data from ClinicalTrials.gov and NHANES. AB - Randomized controlled trials generate high-quality medical evidence. However, the use of unjustified inclusion/exclusion criteria may compromise the external validity of a study. We have introduced a method to assess the population representativeness of related clinical trials using electronic health record (EHR) data. As EHR data may not perfectly represent the real-world patient population, in this work, we further validated the method and its results using the National Health and Nutrition Examination Survey (NHANES) data. We visualized and quantified the differences in the distributions of age, HbA1c, and BMI among the target population of Type 2 diabetes trials, diabetics in NHANES databases, and a convenience sample of patients enrolled in selected Type 2 diabetes trials. The results are consistent with the previous study. PMID- 26262116 TI - Observational Health Data Sciences and Informatics (OHDSI): Opportunities for Observational Researchers. AB - The vision of creating accessible, reliable clinical evidence by accessing the clincial experience of hundreds of millions of patients across the globe is a reality. Observational Health Data Sciences and Informatics (OHDSI) has built on learnings from the Observational Medical Outcomes Partnership to turn methods research and insights into a suite of applications and exploration tools that move the field closer to the ultimate goal of generating evidence about all aspects of healthcare to serve the needs of patients, clinicians and all other decision-makers around the world. PMID- 26262117 TI - Identifying Repetitive Institutional Review Board Stipulations by Natural Language Processing and Network Analysis. AB - The corrections ("stipulations") to a proposed research study protocol produced by an institutional review board (IRB) can often be repetitive across many studies; however, there is no standard set of stipulations that could be used, for example, by researchers wishing to anticipate and correct problems in their research proposals prior to submitting to an IRB. The objective of the research was to computationally identify the most repetitive types of stipulations generated in the course of IRB deliberations. The text of each stipulation was normalized using the natural language processing techniques. An undirected weighted network was constructed in which each stipulation was represented by a node, and each link, if present, had weight corresponding to the TF-IDF Cosine Similarity of the stipulations. Network analysis software was then used to identify clusters in the network representing similar stipulations. The final results were correlated with additional data to produce further insights about the IRB workflow. From a corpus of 18,582 stipulations we identified 31 types of repetitive stipulations. Those types accounted for 3,870 stipulations (20.8% of the corpus) produced for 697 (88.7%) of all protocols in 392 (also 88.7%) of all the CNS IRB meetings with stipulations entered in our data source. A notable peroportion of the corrections produced by the IRB can be considered highly repetitive. Our shareable method relied on a minimal manual analysis and provides an intuitive exploration with theoretically unbounded granularity. Finer granularity allowed for the insight that is anticipated to prevent the need for identifying the IRB panel expertise or any human supervision. PMID- 26262118 TI - Patient-Centered Outcomes Research in Practice: The CAPriCORN Infrastructure. AB - CAPriCORN, the Chicago Area Patient Centered Outcomes Research Network, is one of the eleven PCORI-funded Clinical Data Research Networks. A collaboration of six academic medical centers, a Chicago public hospital, two VA hospitals and a network of federally qualified health centers, CAPriCORN addresses the needs of a diverse community and overlapping populations. To capture complete medical records without compromising patient privacy and confidentiality, the network created policies and mechanisms for patient consultation, central IRB approval, de-identification, de-duplication, and integration of patient data by study cohort, randomization and sampling, re-identification for consent by providers and patients, and communication with patients to elicit patient-reported outcomes through validated instruments. The paper describes these policies and mechanisms and discusses two case studies to prove the feasibility and effectiveness of the network. PMID- 26262119 TI - CA2JU: an Assistive Tool for Children with Cerebral Palsy. AB - This paper presents CA2JU, a hardware/software tool that aims to help individuals with severe speech or language problems in their communication in order to promote their social and digital inclusion. CA2JU is composed of two applications: CA2JU Accelerated, which makes typing faster by suggesting potential words to the user; and CA2JU Illustrated, which automatically converts a sentence of words into a sequence of pictographic symbols, allowing a user familiar with the symbols to verify whether the written sentence is correct. We have implemented, evaluated in a controlled scenario, and deployed CA2JU in a real environment with children with cerebral palsy. In the controlled settings, the results confirm CA2JU Accelerated speed up typing by reducing the number of clicks made by users, and CA2JU Illustrated obtained high accuracy by suggesting the correct pictograms from sentences. In the real scenario, the two use cases show that the children improved their communication and linguistic abilities. PMID- 26262120 TI - Generation of Natural-Language Textual Summaries from Longitudinal Clinical Records. AB - Physicians are required to interpret, abstract and present in free-text large amounts of clinical data in their daily tasks. This is especially true for chronic-disease domains, but holds also in other clinical domains. We have recently developed a prototype system, CliniText, which, given a time-oriented clinical database, and appropriate formal abstraction and summarization knowledge, combines the computational mechanisms of knowledge-based temporal data abstraction, textual summarization, abduction, and natural-language generation techniques, to generate an intelligent textual summary of longitudinal clinical data. We demonstrate our methodology, and the feasibility of providing a free text summary of longitudinal electronic patient records, by generating summaries in two very different domains - Diabetes Management and Cardiothoracic surgery. In particular, we explain the process of generating a discharge summary of a patient who had undergone a Coronary Artery Bypass Graft operation, and a brief summary of the treatment of a diabetes patient for five years. PMID- 26262121 TI - Classification of Contextual Use of Left Ventricular Ejection Fraction Assessments. AB - Knowledge of the left ventricular ejection fraction is critical for the optimal care of patients with heart failure. When a document contains multiple ejection fraction assessments, accurate classification of their contextual use is necessary to filter out historical findings or recommendations and prioritize the assessments for selection of document level ejection fraction information. We present a natural language processing system that classifies the contextual use of both quantitative and qualitative left ventricular ejection fraction assessments in clinical narrative documents. We created support vector machine classifiers with a variety of features extracted from the target assessment, associated concepts, and document section information. The experimental results showed that our classifiers achieved good performance, reaching 95.6% F1-measure for quantitative assessments and 94.2% F1-measure for qualitative assessments in a five-fold cross-validation evaluation. PMID- 26262122 TI - Identification of Patients with Family History of Pancreatic Cancer- Investigation of an NLP System Portability. AB - In this study we have developed a rule-based natural language processing (NLP) system to identify patients with family history of pancreatic cancer. The algorithm was developed in a Unstructured Information Management Architecture (UIMA) framework and consisted of section segmentation, relation discovery, and negation detection. The system was evaluated on data from two institutions. The family history identification precision was consistent across the institutions shifting from 88.9% on Indiana University (IU) dataset to 87.8% on Mayo Clinic dataset. Customizing the algorithm on the the Mayo Clinic data, increased its precision to 88.1%. The family member relation discovery achieved precision, recall, and F-measure of 75.3%, 91.6% and 82.6% respectively. Negation detection resulted in precision of 99.1%. The results show that rule-based NLP approaches for specific information extraction tasks are portable across institutions; however customization of the algorithm on the new dataset improves its performance. PMID- 26262123 TI - Heart Failure Medications Detection and Prescription Status Classification in Clinical Narrative Documents. AB - Angiotensin Converting Enzyme Inhibitors (ACEI) and Angiotensin II Receptor Blockers (ARB) are two common medication classes used for heart failure treatment. The ADAHF (Automated Data Acquisition for Heart Failure) project aimed at automatically extracting heart failure treatment performance metrics from clinical narrative documents, and these medications are an important component of the performance metrics. We developed two different systems to detect these medications, rule-based and machine learning-based. The rule-based system used dictionary lookups with fuzzy string searching and showed successful performance even if our corpus contains various misspelled medications. The machine learning based system uses lexical and morphological features and produced similar results. The best performance was achieved when combining the two methods, reaching 99.3% recall and 98.8% precision. To determine the prescription status of each medication (i.e., active, discontinued, or negative), we implemented a SVM classifier with lexical features and achieved good performance, reaching 95.49% accuracy, in a five-fold cross-validation evaluation. PMID- 26262124 TI - Classifying the Indication for Colonoscopy Procedures: A Comparison of NLP Approaches in a Diverse National Healthcare System. AB - In order to measure the level of utilization of colonoscopy procedures, identifying the primary indication for the procedure is required. Colonoscopies may be utilized not only for screening, but also for diagnostic or therapeutic purposes. To determine whether a colonoscopy was performed for screening, we created a natural language processing system to identify colonoscopy reports in the electronic medical record system and extract indications for the procedure. A rule-based model and three machine-learning models were created using 2,000 manually annotated clinical notes of patients cared for in the Department of Veterans Affairs. Performance of the models was measured and compared. Analysis of the models on a test set of 1,000 documents indicates that the rule-based system performance stays fairly constant as evaluated on training and testing sets. However, the machine learning model without feature selection showed significant decrease in performance. Therefore, rule-based classification system appears to be more robust than a machine-learning system in cases when no feature selection is performed. PMID- 26262125 TI - Automatically Expanding the Synonym Set of SNOMED CT using Wikipedia. AB - Clinical terminologies and ontologies are often used in natural language processing/understanding tasks as a method for semantically tagging text. One ontology commonly used for this task is SNOMED CT. Natural language is rich and varied: many different combinations of words may be used to express the same idea. It is therefore essential that ontologies and terminologies have a rich set of synonyms. One source of synonyms is Wikipedia. We examine methods for aligning concepts in SNOMED CT with articles in Wikipedia so that newly-found synonyms may be added to SNOMED CT. Our experiments show promising results and provide guidance to researchers who wish to use Wikipedia for similar tasks. PMID- 26262126 TI - Named Entity Recognition in Chinese Clinical Text Using Deep Neural Network. AB - Rapid growth in electronic health records (EHRs) use has led to an unprecedented expansion of available clinical data in electronic formats. However, much of the important healthcare information is locked in the narrative documents. Therefore Natural Language Processing (NLP) technologies, e.g., Named Entity Recognition that identifies boundaries and types of entities, has been extensively studied to unlock important clinical information in free text. In this study, we investigated a novel deep learning method to recognize clinical entities in Chinese clinical documents using the minimal feature engineering approach. We developed a deep neural network (DNN) to generate word embeddings from a large unlabeled corpus through unsupervised learning and another DNN for the NER task. The experiment results showed that the DNN with word embeddings trained from the large unlabeled corpus outperformed the state-of-the-art CRF's model in the minimal feature engineering setting, achieving the highest F1-score of 0.9280. Further analysis showed that word embeddings derived through unsupervised learning from large unlabeled corpus remarkably improved the DNN with randomized embedding, denoting the usefulness of unsupervised feature learning. PMID- 26262127 TI - Identifying Patients with Depression Using Free-text Clinical Documents. AB - About 1 in 10 adults are reported to exhibit clinical depression and the associated personal, societal, and economic costs are significant. In this study, we applied the MTERMS NLP system and machine learning classification algorithms to identify patients with depression using discharge summaries. Domain experts reviewed both the training and test cases, and classified these cases as depression with a high, intermediate, and low confidence. For depression cases with high confidence, all of the algorithms we tested performed similarly, with MTERMS' knowledge-based decision tree slightly better than the machine learning classifiers, achieving an F-measure of 89.6%. MTERMS also achieved the highest F measure (70.6%) on intermediate confidence cases. The RIPPER rule learner was the best performing machine learning method, with an F-measure of 70.0%, and a higher precision but lower recall than MTERMS. The proposed NLP-based approach was able to identify a significant portion of the depression cases (about 20%) that were not on the coded diagnosis list. PMID- 26262128 TI - An Approach for Automatic Classification of Radiology Reports in Spanish. AB - Automatic detection of relevant terms in medical reports is useful for educational purposes and for clinical research. Natural language processing (NLP) techniques can be applied in order to identify them. In this work we present an approach to classify radiology reports written in Spanish into two sets: the ones that indicate pathological findings and the ones that do not. In addition, the entities corresponding to pathological findings are identified in the reports. We use RadLex, a lexicon of English radiology terms, and NLP techniques to identify the occurrence of pathological findings. Reports are classified using a simple algorithm based on the presence of pathological findings, negation and hedge terms. The implemented algorithms were tested with a test set of 248 reports annotated by an expert, obtaining a best result of 0.72 F1 measure. The output of the classification task can be used to look for specific occurrences of pathological findings. PMID- 26262129 TI - Automated Learning of Temporal Expressions. AB - Clinical notes contain important temporal information that are critical for making clinical diagnosis and treatment as well as for retrospective analyses. Manually created regular expressions are commonly used for the extraction of temporal information; however, this can be a time consuming and brittle approach. We describe a novel algorithm for automatic learning of regular expressions in recognizing temporal expressions. Five classes of temporal expressions are identified. Keywords specific to those classes are used to retrieve snippets of text representing the same keywords in context. Those snippets are used for Regular Expression Discovery Extraction (REDEx). These learned regular expressions are then evaluated using 10-fold cross validation. Precision and recall are very high, above 0.95 for most classes. PMID- 26262130 TI - Identifying Diseases, Drugs, and Symptoms in Twitter. AB - Social media sites, such as Twitter, are a rich source of many kinds of information, including health-related information. Accurate detection of entities such as diseases, drugs, and symptoms could be used for biosurveillance (e.g. monitoring of flu) and identification of adverse drug events. However, a critical assessment of performance of current text mining technology on Twitter has not been done yet in the medical domain. Here, we study the development of a Twitter data set annotated with relevant medical entities which we have publicly released. The manual annotation results show that it is possible to perform high quality annotation despite of the complexity of medical terminology and the lack of context in a tweet. Furthermore, we have evaluated the capability of state-of the-art approaches to reproduce the annotations in the data set. The best methods achieve F-scores of 55-66%. The data analysis and the preliminary results provide valuable insights on identifying medical entities in Twitter for various applications. PMID- 26262131 TI - Improving Preventive Healthcare with an User-centric Mobile Tele-monitoring Model. AB - Chronic diseases are an important field to tackle due to increasing healthcare risk factors, including population nutritional habits, lack of physical exercise, and population aging. Diabetes mellitus, hypertension, and obesity currently affect millions of people, and this statistic grows every year and is responsible for numerous deaths everyday. Many of those deaths could be delayed by following a steady monitoring strategy over such a population, which would prevent vital signs from reaching critical stages and providing knowledge for these patients about their health. This paper introduces Mobilicare, a mobile health promotion system designed to: (i) monitor remotely a patient's vital signs in real time; (ii) support a health service in a Healthcare Center; and (iii) allow self awareness of the disease and improve motivation. Our approach was applied to two distinct chronic patient management programs. The results showed the commitment of elder patients and the contribution of Mobilicare to the maintenance of a patient's health stability. PMID- 26262132 TI - Calculation of Cardiac Kinetic Energy Index from PET images. AB - Cardiac function can be assessed from displacement measurements in imaging modalities from nuclear medicine Using positron emission tomography (PET) image sequences with Rubidium-82, we propose and estimate the total Kinetic Energy Index (KEf) obtained from the velocity field, which was calculated using 3D optical flow(OF) methods applied over the temporal image sequence. However, it was found that the brightness of the image varied unexpectedly between frames, violating the constant brightness assumption of the OF method and causing large errors in estimating the velocity field. Therefore total brightness was equalized across image frames and the adjusted configuration tested with rest perfusion images acquired from individuals with normal (n=30) and low (n=33) cardiac function. For these images KEf was calculated as 0.5731+/-0.0899 and 0.3812+/ 0.1146 for individuals with normal and low cardiac function respectively. The ability of KEf to properly classify patients into the two groups was tested with a ROC analysis, with area under the curve estimated as 0.906. To our knowledge this is the first time that KEf has been applied to PET images. PMID- 26262133 TI - TCGA4U: A Web-Based Genomic Analysis Platform To Explore And Mine TCGA Genomic Data For Translational Research. AB - Large-scale human cancer genomics projects, such as TCGA, generated large genomics data for further study. Exploring and mining these data to obtain meaningful analysis results can help researchers find potential genomics alterations that intervene the development and metastasis of tumors. We developed a web-based gene analysis platform, named TCGA4U, which used statistics methods and models to help translational investigators explore, mine and visualize human cancer genomic characteristic information from the TCGA datasets. Furthermore, through Gene Ontology (GO) annotation and clinical data integration, the genomic data were transformed into biological process, molecular function, cellular component and survival curves to help researchers identify potential driver genes. Clinical researchers without expertise in data analysis will benefit from such a user-friendly genomic analysis platform. PMID- 26262135 TI - Managing OMICS-Data: Considerations for the Design of a Clinical Research IT Infrastructure. AB - Biomarker-based translational research enables deep insight into cellular processes and human diseases. As a result, high-throughput technologies promulgating a fast and cost-effective generation of data are widely used to advance our understanding in the molecular background of individuals. However, the increasing volume and complexity of data increases the need for sustainable infrastructures and state-of-the-art tools allowing management, analysis, and integration of OMICS data. To address these challenges, we have performed site visits of core facilities with a focus on high-throughput technologies to explore their (IT) infrastructure, organizational aspects, and data management strategies. Different stakeholders were interviewed regarding requirements and needs for dealing with high-throughput data. We have identified four different fields of action: (1) the interface from biorepositories to service providers of high-throughput technologies, (2) aspects within services providers, (3) the interface from service providers to bioinformatical analysis, and (4) organizational and other aspects. For each field, recommendations and strategies were developed for implementation of a seamless pipeline from biorepositories to highly specialized high-throughput laboratories including the sustainable management and integration of OMICS data. PMID- 26262134 TI - Conceptual Knowledge Discovery in Databases for Drug Combinations Predictions in Malignant Melanoma. AB - The worldwide incidence of melanoma is rising faster than any other cancer, and prognosis for patients with metastatic disease is poor. Current targeted therapies are limited in their durability and/or effect size in certain patient populations due to acquired mechanisms of resistance. Thus, the development of synergistic combinatorial treatment regimens holds great promise to improve patient outcomes. We have previously shown that a model for in-silico knowledge discovery, Translational Ontology-anchored Knowledge Discovery Engine (TOKEn), is able to generate valid relationships between bimolecular and clinical phenotypes. In this study, we have aggregated observational and canonical knowledge consisting of melanoma-related biomolecular entities and targeted therapeutics in a computationally tractable model. We demonstrate here that the explicit linkage of therapeutic modalities with biomolecular underpinnings of melanoma utilizing the TOKEn pipeline yield a set of informed relationships that have the potential to generate combination therapy strategies. PMID- 26262136 TI - Virtual Microscopy Large Slide Automated Acquisition: Error Analysis and Validation. AB - The aim of this work is to assess and analyze the discrepancies introduced in the reconstruction of an entire tumoral bone slice from multiple field acquisitions of a large microscopy slide. The reconstruction tends to preserve the original structural information and its error is estimated by comparing the reconstructed images of eight samples against single pictures of these samples. This comparison is held using the Structural Similarity index. The measurements show that smaller samples yield better results. The detected errors are introduced by the insufficiently corrected optical distortion caused by the camera lens, which tends to accumulate along the sample. Nevertheless, the maximum error encountered does not exceed 0.39 mm, which is smaller than the maximum tolerable error for the intended application, stated in 1 mm. PMID- 26262137 TI - Do interoperable national information systems enhance availability of data to assess the effect of scale-up of HIV services on health workforce deployment in resource-limited countries? AB - Sub-Saharan Africa (SSA) bears the heaviest burden of the HIV epidemic. Health workers play a critical role in the scale-up of HIV programs. SSA also has the weakest information and communication technology (ICT) infrastructure globally. Implementing interoperable national health information systems (HIS) is a challenge, even in developed countries. Countries in resource-limited settings have yet to demonstrate that interoperable systems can be achieved, and can improve quality of healthcare through enhanced data availability and use in the deployment of the health workforce. We established interoperable HIS integrating a Master Facility List (MFL), District Health Information Software (DHIS2), and Human Resources Information Systems (HRIS) through application programmers interfaces (API). We abstracted data on HIV care, health workers deployment, and health facilities geo-coordinates. Over 95% of data elements were exchanged between the MFL-DHIS and HRIS-DHIS. The correlation between the number of HIV positive clients and nurses and clinical officers in 2013 was R2=0.251 and R2=0.261 respectively. Wrong MFL codes, data type mis-match and hyphens in legacy data were key causes of data transmission errors. Lack of information exchange standards for aggregate data made programming time-consuming. PMID- 26262138 TI - Improving Clinical Decisions on T2DM Patients Integrating Clinical, Administrative and Environmental Data. AB - This work describes an integrated informatics system developed to collect and display clinically relevant data that can inform physicians and researchers about Type 2 Diabetes Mellitus (T2DM) patient clinical pathways and therapy adherence. The software we developed takes data coming from the electronic medical record (EMR) of the IRCCS Fondazione Maugeri (FSM) hospital of Pavia, Italy, and combines the data with administrative, pharmacy drugs (purchased from the local healthcare agency (ASL) of the Pavia area), and open environmental data of the same region. By using different use cases, we explain the importance of gathering and displaying the data types through a single informatics tool: the use of the tool as a calculator of risk factors and indicators to improve current detection of T2DM, a generator of clinical pathways and patients' behaviors from the point of view of the hospital care management, and a decision support tool for follow up visits. The results of the performed data analysis report how the use of the dashboard displays meaningful clinical decisions in treating complex chronic diseases and might improve health outcomes. PMID- 26262139 TI - Architecture to Summarize Patient-Level Data Across Borders and Countries. AB - Translational medicine is becoming fundamental in promoting information flow between basic research and clinical practice, and in improving patients' health. The need for efficient systems to process and share information from multiple sources--including distinct areas of medicine--is a pressing need in biomedical research. Nevertheless, healthcare information systems are fragmented over different databases, medical institutions, and geographical locations. There are already several approaches to tackle this problem based on centralized or distributed solutions. Nonetheless, mainly due to privacy reasons, these models only work for specific silos. In this paper, we present a new ecosystem for connecting database owners and researchers. Our approach consists of gathering, via a common fingerprint, an extensive characterization of dispersed databases. This fingerprint typically contains high-level aggregated information addressing questions at a population level and allowing, for instance, quick identification of databases with data that may help to answer a specific research question. This work is being conducted in the context of EMIF (European Medical Information Framework), an IMI (The Innovative Medicines Initiative) joint undertaking funded project, wherein the Catalogue is being used to collect data from cohorts and Electronic Health Record systems of several European countries. PMID- 26262140 TI - A Cloud-Based Infrastructure for Feedback-Driven Training and Image Recognition. AB - Advanced techniques in machine learning combined with scalable "cloud" computing infrastructure are driving the creation of new and innovative health diagnostic applications. We describe a service and application for performing image training and recognition, tailored to dermatology and melanoma identification. The system implements new machine learning approaches to provide a feedback-driven training loop. This training sequence enhances classification performance by incrementally retraining the classifier model from expert responses. To easily provide this application and associated web service to clinical practices, we also describe a scalable cloud infrastructure, deployable in public cloud infrastructure and private, on-premise systems. PMID- 26262141 TI - A Two-stage Dynamic Model to Enable Updating of Clinical Risk Prediction from Longitudinal Health Record Data: Illustrated with Kidney Function. AB - We demonstrate the use of electronic records and repeated measures of risk factors therein, to enable deeper understanding of the relationship between the full longitudinal trajectory of risk factors and outcomes. To illustrate, dynamic mixed effect modelling is used to summarise the level, trend and monitoring intensity of kidney function. The output from this model then forms covariates for a recurrent event Cox proportional hazards model for predicting adverse events (AE). Using data from Salford, UK, our multivariate model finds that steeper declines in kidney function raise the hazard of AE (HR: 1.13, 95% CI (1.05, 1.22)). There is a non-proportional relationship between the hazard of AE and the monitoring intensity of kidney function. Neither of these variables would be present in a classical risk prediction model.. This work illustrates the potential of using the full longitudinal profile of risk factors, rather than just their level. There is an opportunity for deep statistical learning leading to rich clinical insight using longitudinal signals in electronic data. PMID- 26262142 TI - Development and preliminary validation of a dynamic, patient-tailored method to detect abnormal laboratory test results. AB - Laboratory test results in primary care are flagged as 'abnormal' when they fall outside a population-based Reference Interval (RI), typically generating many alerts with a low specificity. In order to decrease alert frequency while retaining clinical relevance, we developed a method to assess dynamic, patient tailored RIs based on mixed-effects linear regression models. Potassium test results from primary care were used as proof-of-concept test bed. Clinical relevance was assessed via a survey administered to general practitioners (GPs). Overall, the dynamic, patient-tailored method and the combination of both methods flagged 20% and 36% fewer values as abnormal than the population-based method. Nineteen out of 43 invited GPs (44%) completed the survey. The population-based method yielded a better sensitivity than the patient-tailored and the combined methods (0.51 vs 0.41 and 0.38, respectively) but a lower PPV (0.66 vs 0.67 and 0.76, respectively). We conclude that a combination of population-based and patient-tailored RIs can improve the detection of abnormal laboratory results. We suggest that lab values outside both RIs be flagged with high priority in clinical practice. PMID- 26262143 TI - Automated Detection of Postoperative Surgical Site Infections Using Supervised Methods with Electronic Health Record Data. AB - The National Surgical Quality Improvement Project (NSQIP) is widely recognized as "the best in the nation" surgical quality improvement resource in the United States. In particular, it rigorously defines postoperative morbidity outcomes, including surgical adverse events occurring within 30 days of surgery. Due to its manual yet expensive construction process, the NSQIP registry is of exceptionally high quality, but its high cost remains a significant bottleneck to NSQIP's wider dissemination. In this work, we propose an automated surgical adverse events detection tool, aimed at accelerating the process of extracting postoperative outcomes from medical charts. As a prototype system, we combined local EHR data with the NSQIP gold standard outcomes and developed machine learned models to retrospectively detect Surgical Site Infections (SSI), a particular family of adverse events that NSQIP extracts. The built models have high specificity (from 0.788 to 0.988) as well as very high negative predictive values (>0.98), reliably eliminating the vast majority of patients without SSI, thereby significantly reducing the NSQIP extractors' burden. PMID- 26262144 TI - Mining Temporal and Data Constraints Associated with Outcomes for Care Pathways. AB - A care/clinical pathway defines a standardized care process for a specific patient group, which consists of clinical goals, activities, data attributes, and constraints describing temporal dependencies and data preconditions of the activities. The constraints, which are the key elements to represent the best practices, are difficult to define due to the variations in different regions and populations. In this paper, we propose an approach to discover temporal and data constraints that are correlated with clinical outcomes for care pathways. For each activity of interest, we extract a set of associated event-condition-action (ECA) rules from electronic medical records (EMR) to represent the temporal and data preconditions of the activity, by using our modified association rule mining algorithm. Then the best ECA rule that is significantly more likely to lead to a positive outcome is translated into the constraint on the activity. The approach has been applied to real-world EMR, and discovered meaningful constraints for different groups of type 2 diabetes patients, which can be used to provide decision support during individual patient care. PMID- 26262145 TI - Acquiring Plausible Predications from MEDLINE by Clustering MeSH Annotations. AB - The massive accumulation of biomedical knowledge is reflected by the growth of the literature database MEDLINE with over 23 million bibliographic records. All records are manually indexed by MeSH descriptors, many of them refined by MeSH subheadings. We use subheading information to cluster types of MeSH descriptor co occurrences in MEDLINE by processing co-occurrence information provided by the UMLS. The goal is to infer plausible predicates to each resulting cluster. In an initial experiment this was done by grouping disease-pharmacologic substance co occurrences into six clusters. Then, a domain expert manually performed the assignment of meaningful predicates to the clusters. The mean accuracy of the best ten generated biomedical facts of each cluster was 85%. This result supports the evidence of the potential of MeSH subheadings for extracting plausible medical predications from MEDLINE. PMID- 26262146 TI - Effects of Plasma Transfusion on Perioperative Bleeding Complications: A Machine Learning Approach. AB - Perioperative bleeding (PB) is associated with increased patient morbidity and mortality, and results in substantial health care resource utilization. To assess bleeding risk, a routine practice in most centers is to use indicators such as elevated values of the International Normalized Ratio (INR). For patients with elevated INR, the routine therapy option is plasma transfusion. However, the predictive accuracy of INR and the value of plasma transfusion still remains unclear. Accurate methods are therefore needed to identify early the patients with increased risk of bleeding. The goal of this work is to apply advanced machine learning methods to study the relationship between preoperative plasma transfusion (PPT) and PB in patients with elevated INR undergoing noncardiac surgery. The problem is cast under the framework of causal inference where robust meaningful measures to quantify the effect of PPT on PB are estimated. Results show that both machine learning and standard statistical methods generally agree that PPT negatively impacts PB and other important patient outcomes. However, machine learning methods show significant results, and machine learning boosting methods are found to make less errors in predicting PB. PMID- 26262147 TI - On the Automated Segmentation of Epicardial and Mediastinal Cardiac Adipose Tissues Using Classification Algorithms. AB - The quantification of fat depots on the surroundings of the heart is an accurate procedure for evaluating health risk factors correlated with several diseases. However, this type of evaluation is not widely employed in clinical practice due to the required human workload. This work proposes a novel technique for the automatic segmentation of cardiac fat pads. The technique is based on applying classification algorithms to the segmentation of cardiac CT images. Furthermore, we extensively evaluate the performance of several algorithms on this task and discuss which provided better predictive models. Experimental results have shown that the mean accuracy for the classification of epicardial and mediastinal fats has been 98.4% with a mean true positive rate of 96.2%. On average, the Dice similarity index, regarding the segmented patients and the ground truth, was equal to 96.8%. Therfore, our technique has achieved the most accurate results for the automatic segmentation of cardiac fats, to date. PMID- 26262148 TI - Fusing Heterogeneous Data for Alzheimer's Disease Classification. AB - In multi-view learning, multimodal representations of a real world object or situation are integrated to learn its overall picture. Feature sets from distinct data sources carry different, yet complementary, information which, if analysed together, usually yield better insights and more accurate results. Neuro degenerative disorders such as dementia are characterized by changes in multiple biomarkers. This work combines the features from neuroimaging and cerebrospinal fluid studies to distinguish Alzheimer's disease patients from healthy subjects. We apply statistical data fusion techniques on 101 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We examine whether fusion of biomarkers helps to improve diagnostic accuracy and how the methods compare against each other for this problem. Our results indicate that multimodal data fusion improves classification accuracy. PMID- 26262149 TI - Towards Constructing a New Taxonomy for Psychiatry Using Self-reported Symptoms. AB - The Diagnostic and Statistical Manual (DSM) has served as the gold standard for psychiatric diagnosis for the past several decades in the USA, and DSM diagnoses mirror mental health and substance abuse diagnoses in ICD-9 and ICD-10. However, DSM diagnoses have severe limitations when used as phenotypes for studies of the pathophysiology underlying mental disorders, as well as for clinical treatment and research. In this paper, we use a novel approach of deconstructing DSM diagnostic criteria, and using expert knowledge to inform feature selection for unsupervised machine learning. We are able to identify clusters of symptoms that stratify subjects with the same DSM disorders into cohorts with increased clinical and biological homogeneity. These findings suggest that itemized self report symptom data should inform a new taxonomy for psychiatry, and will enhance the bi-directional translation of knowledge from the bench to the clinic through a common terminology. PMID- 26262150 TI - A Multi-Relational Model for Depression Relapse in Patients with Bipolar Disorder. AB - Bipolar Disorder (BD) is a chronic and disabling disease that usually appears around 20 to 30 years old. Patients who suffer with BD may struggle for years to achieve a correct diagnosis, and only 50% of them generally receive adequate treatment. In this work we apply a machine learning technique called Inductive Logic Programming (ILP) in order to model relapse and no-relapse patients in a first attempt in this area to improve diagnosis and optimize psychiatrists' time spent with patients. We use ILP because it is well suited for our multi relational dataset and because a human can easily interpret the logical rules produced. Our classifiers can predict relapse cases with 92% Recall and no relapse cases with 73% Recall. The rules and variable theories generated by ILP reproduce some findings from the scientific literature. The generated multi relational models can be directly interpreted by clinicians and researchers, and also open space to research biological mechanisms and interventions. PMID- 26262151 TI - Thermal Signal Analysis for Breast Cancer Risk Verification. AB - Breast cancer is the second most common cancer in the world. Currently, there are no effective methods to prevent this disease. However, early diagnosis increases chances of remission. Breast thermography is an option to be considered in screening strategies. This paper proposes a new dynamic breast thermography analysis technique in order to identify patients at risk for breast cancer. Thermal signals from patients of the Antonio Pedro University Hospital (HUAP), available at the Mastology Database for Research with Infrared Image - DMR-IR were used to validate the study. First, each patient's images are registered. Then, the breast region is divided into subregions of 3x3 pixels and the average temperature from each of these regions is observed in all images of the same patient. Features of the thermal signals of such subregions are calculated. Then, the k-means algorithm is applied over feature vectors building two clusters. Silhouette index, Davies-Bouldin index and Calinski-Harabasz index are applied to evaluate the clustering. The test results showed that the methodology presented in this paper is able to identify patients with breast cancer. Classification techniques have been applied on the index values and 90.90% hit rate has been achieved. PMID- 26262152 TI - Time-Series Data Analysis of Long-Term Home Blood Pressure Measurements in Relation to Lifestyle. AB - We conducted a long-term time-series analysis of an individual's home blood pressure measurements, stored on a personal healthcare system in cloud, relative to the individual's life-style. In addition to daily scattering, apparent seasonal variations were observed in both systolic and diastolic blood pressure measurements. We examined the effect of seasonal variations on the outcome of a healthcare data mining process that extracts rules between blood pressure measurements and life-style components such as exercise and diet, and found that the daily blood pressure data approached a normal distribution when adjusted for the seasonal variations. This implies that an adjustment is desirable in order to produce appropriate rules in the healthcare data mining process. PMID- 26262153 TI - The Improvement of Dental Posture Using Personalized Biofeedback. AB - BACKGROUND: Dentists are subject to staying in static or awkward postures for long periods due to their highly concentrated work. OBJECTIVES: This study describes a real-time personalized biofeedback system developed for dental posture training with the use of vibrotactile biofeedback. METHODS: The real-time personalized biofeedback system was an integrated solution that comprised of two components: 1) a wearable device that contained an accelerometer sensor for measuring the tilt angle of the body (input) and provided real-time vibrotactile biofeedback (output); and 2) software for data capturing, processing, and personalized biofeedback generation. The implementation of real-time personalized vibrotactile feedback was computed using Hidden Markov Models (HMMs). For the test case, we calculated the probability and log-likelihood of the test movements under the Work related Musculoskeletal Disorders (WMSD) and non-WMSD HMMs. The vibrotactile biofeedback was provided to the user via a wearable device for a WMSD-predicted case. In the system evaluation, a randomized crossover trial was conducted to compare dental posture measure using tilt angles of the upper back and muscle activities of those dental students that received vibrotactile biofeedback from the system with the control group against the dental students who received no feedback. RESULTS: The participants who received feedback from the system had a lower tilt angle at 10th, 50th, and 90th percentiles of Backx and Backy, as well as muscular load, which were statistically different (p<0.05) from those who received no feedback from the system. CONCLUSIONS: The results presented here demonstrate that a personalized biofeedback system for posture training in dental students is feasible and associated with quantitative improvements of the dental posture. PMID- 26262154 TI - Using social connection information to improve opinion mining: Identifying negative sentiment about HPV vaccines on Twitter. AB - The manner in which people preferentially interact with others like themselves suggests that information about social connections may be useful in the surveillance of opinions for public health purposes. We examined if social connection information from tweets about human papillomavirus (HPV) vaccines could be used to train classifiers that identify anti-vaccine opinions. From 42,533 tweets posted between October 2013 and March 2014, 2,098 were sampled at random and two investigators independently identified anti-vaccine opinions. Machine learning methods were used to train classifiers using the first three months of data, including content (8,261 text fragments) and social connections (10,758 relationships). Connection-based classifiers performed similarly to content-based classifiers on the first three months of training data, and performed more consistently than content-based classifiers on test data from the subsequent three months. The most accurate classifier achieved an accuracy of 88.6% on the test data set, and used only social connection features. Information about how people are connected, rather than what they write, may be useful for improving public health surveillance methods on Twitter. PMID- 26262155 TI - Syndromic Surveillance of Infectious Diseases meets Molecular Epidemiology in a Workflow and Phylogeographic Application. AB - Traditionally, epidemiologists have counted cases and groups of symptoms. Modeling on these data consists of predicting expansion or contraction in the number of cases over time in epidemic curves or compartment models. Geography is considered a variable when these data are presented in choropleth maps. These approaches have significant drawbacks if the cases counted are not accurately diagnosed. For example, most regional public health authorities count influenza like illnesses (ILI). Cases of these diseases are designated as ILI if the patient exhibits fever, respiratory symptoms, and perhaps gastrointestinal symptoms. Several molecular epidemiological studies have shown that there are many pathogens that cause these symptoms and the relative proportions of these pathogens change over time and space. One way to bridge the gap between syndromic and genetic surveillance of infectious diseases is to compare signals of symptoms to pathogens recorded in molecular databases. We present a web-based workflow application that uses chief complaints found in the public Twitter feed as a syndromic surveillance tool and connects outbreak signals in these data to pathogens historically known to circulate in the same area. For the pathogen(s) of interest, we provide Genbank links to metadata and sequences in a workflow for phylogeographic analysis and visualization. The visualizations provide information on the geographic traffic of the spread of the pathogens and places that are hubs for their transport. PMID- 26262156 TI - Fingerprinting Biomedical Terminologies--Automatic Classification and Visualization of Biomedical Vocabularies through UMLS Semantic Group Profiles. AB - OBJECTIVES: To explore automatic methods for the classification of biomedical vocabularies based on their content. METHODS: We create semantic group profiles for each source vocabulary in the UMLS and compare the vectors using a Euclidian distance. We explore several techniques for visualizing individual semantic group profiles and the entire distance matrix, including donut pie charts, heatmaps, dendrograms and networks. RESULTS: We provide donut pie charts for individual source vocavularies, as well as a heatmap, dendrogram and network for a subset of 78 vocabularies from the UMLS. CONCLUSIONS: Our approach to fingerprinting biomedical terminologies is completely automated and can easily be applied to all source vocabularies in the UMLS, including upcoming versions of the UMLS. It supports the exploration, selection and comparison of the biomedical terminologies integrated into the UMLS. The visualizations are available at (http://mor.-nlm.nih.gov/pubs/supp/2015-medinfo-br/index.html). PMID- 26262157 TI - Harmonizing Nursing Terminologies. AB - In this paper, the authors report on a study aimed at harmonising two nursing terminologies, the Clinical Care Classification (CCC) and the International Classification for Nursing Practice (ICNP(r)). As the electronic health record evolves and the need for interoperability extends beyond local and national borders, a degree of standardisation across healthcare terminologies become essential. Harmonising across terminologies results in a) increased consensus relating to domain content and b) improvements in the terminologies involved. Findings from this study suggest that there is much overlap of content in nursing terminologies. The continued harmonisation between nursing terminologies and other healthcare terminologies are recommended to achieve international interoperability. PMID- 26262158 TI - Developing a National-Level Concept Dictionary for EHR Implementations in Kenya. AB - The increasing adoption of Electronic Health Records (EHR) by developing countries comes with the need to develop common terminology standards to assure semantic interoperability. In Kenya, where the Ministry of Health has rolled out an EHR at 646 sites, several challenges have emerged including variable dictionaries across implementations, inability to easily share data across systems, lack of expertise in dictionary management, lack of central coordination and custody of a terminology service, inadequately defined policies and processes, insufficient infrastructure, among others. A Concept Working Group was constituted to address these challenges. The country settled on a common Kenya data dictionary, initially derived as a subset of the Columbia International eHealth Laboratory (CIEL)/Millennium Villages Project (MVP) dictionary. The initial dictionary scope largely focuses on clinical needs. Processes and policies around dictionary management are being guided by the framework developed by Bakhshi-Raiez et al. Technical and infrastructure-based approaches are also underway to streamline workflow for dictionary management and distribution across implementations. Kenya's approach on comprehensive common dictionary can serve as a model for other countries in similar settings. PMID- 26262159 TI - Evaluation of Herbal and Dietary Supplement Resource Term Coverage. AB - The use of Complementary and Alternative Medicine (CAM) is increasingly popular in places like North America and Europe where western medicine is primarily practiced. People are consuming herbal and dietary supplements along with western medications simultaneously. Sometimes, supplements and drugs react with one another via antagonistic or potentiation actions of the drug or supplement resulting in an adverse event. Unfortunately, it is not easy to study drug supplement interactions without a standard terminology to describe herbal and dietary supplements. This pilot study investigated coverage of supplement databases to one another as well as coverage by the Unified Medical Language System (UMLS) and RxNorm for supplement terms. We found that none of the supplement databases completely covers supplement terms. UMLS, MeSH, SNOMED CT, RxNorm and NDF-RT cover 54%, 40%, 32%, 22% and 14% of supplement concepts, respectively. NDF-RT provides some value for grouping supplements into drug classes. Enhancing our understanding of the gap between the traditional biomedical terminology systems and supplement terms could lead to the development of a comprehensive terminology resources for supplements, and other secondary uses such as better detection and extraction of drug-supplement interactions. PMID- 26262160 TI - Semantic Alignment between ICD-11 and SNOMED CT. AB - Due to fundamental differences in design and editorial policies, semantic interoperability between two de facto standard terminologies in the healthcare domain--the International Classification of Diseases (ICD) and SNOMED CT (SCT), requires combining two different approaches: (i) axiom-based, which states logically what is universally true, using an ontology language such as OWL; (ii) rule-based, expressed as queries on the axiom-based knowledge. We present the ICD SCT harmonization process including: a) a new architecture for ICD-11, b) a protocol for the semantic alignment of ICD and SCT, and c) preliminary results of the alignment applied to more than half the domain currently covered by the draft ICD-11. PMID- 26262161 TI - Extending the coverage of phenotypes in SNOMED CT through post-coordination. AB - OBJECTIVES: To extend the coverage of phenotypes in SNOMED CT through post coordination. METHODS: We identify frequent modifiers in terms from the Human Phenotype Ontology (HPO), which we associate with templates for post-coordinated expressions in SNOMED CT. RESULTS: We identified 176 modifiers, created 12 templates, and generated 1,617 post-coordinated expressions. CONCLUSIONS: Through this novel approach, we can increase the current number of mappings by 50%. PMID- 26262162 TI - A model-Driven Approach to Customize the Vocabulary of Communication Boards: Towards More Humanization of Health Care. AB - OBJECTIVE: This work presents a Modeling Language and its technological infrastructure to customize the vocabulary of Communication Boards (CB), which are important tools to provide more humanization of health care. METHOD: Using a technological infrastructure based on Model-Driven Development (MDD) approach, our Modelin Language (ML) creates an abstraction layer between users (e.g., health professionals such as an audiologist or speech therapist) and application code. Moreover, the use of a metamodel enables a syntactic corrector for preventing creation of wrong models. RESULTS: Our ML and metamodel enable more autonomy for health professionals in creating customized CB because it abstracts complexities and permits them to deal only with the domain concepts (e.g., vocabulary and patient needs). Additionally, our infrastructure provides a configuration file that can be used to share and reuse models. This way, the vocabulary modelling effort will decrease our time since people share vocabulary models. CONCLUSION: Our study provides an infrastructure that aims to abstract the complexity of CB vocabulary customization, giving more autonomy to health professionals when they need customizing, sharing and reusing vocabularies for CB. PMID- 26262163 TI - Pain Documentation: Validation of a Reference Model. AB - Over the last decade, interoperability of the Electronic Health Record (EHR) is becoming more of a reality. However, inconsistencies in documentation such as pain are considered a barrier to obtaining this goal. In order to be able to remedy this issue, it is necessary to validate reference models that have been created based upon requirements defined by Health Level 7 (HL7), Logical Names and Codes (LOINC) and the Intermountain Clinical Element Model using external published sources and guidelines. Using pain as an example of complex and inconsistent documentation, it was found that the reference model based upon these standards is valid because the data elements identified are broad and can meet the needs of each sub-domain within the primary domain of pain. PMID- 26262164 TI - Consumer Health Information Needs and Question Classification: Analysis of Hypertension Related Questions Asked by Consumers on a Chinese Health Website. AB - This study built up a classification schema of consumer health questions which consisted of 48 quaternary categories and 35 annotation rules. Using such a schema, we manually classified 2,000 questions randomly selected from nearly 100 thousand hypertension-related messages posted by consumers on a Chinese health website to analyze the information needs of health consumers. The results showed questions in the categories of treatment, diagnosis, healthy lifestyle, management, epidemiology, and health provider choosing were 48.1%, 23.8%, 11.9%, 5.2%, 9.0%, and 1.9% respectively. The comparison of the questions asked by consumers and physicians showed that their health information needs were significantly different (P<0.0001). PMID- 26262165 TI - Generating and Executing Complex Natural Language Queries across Linked Data. AB - With the recent and intensive research in the biomedical area, the knowledge accumulated is disseminated through various knowledge bases. Links between these knowledge bases are needed in order to use them jointly. Linked Data, SPARQL language, and interfaces in Natural Language question-answering provide interesting solutions for querying such knowledge bases. We propose a method for translating natural language questions in SPARQL queries. We use Natural Language Processing tools, semantic resources, and the RDF triples description. The method is designed on 50 questions over 3 biomedical knowledge bases, and evaluated on 27 questions. It achieves 0.78 F-measure on the test set. The method for translating natural language questions into SPARQL queries is implemented as Perl module available at http://search.cpan.org/ thhamon/RDF-NLP-SPARQLQuery. PMID- 26262166 TI - Analyzing Operative Note Structure in Development of a Section Header Resource. AB - Operative notes contain essential details of surgical procedures and are an important form of clinical documentation. Sections within operative notes segment provide high level note structure. We evaluated the HL7 Implementation Guide for Clinical Document Architecture Release 2.0 Operative Note Draft Standard for Trial Use (HL7-ON DSTU) Release 1 as well as Logical Observation Identifiers Names and Codes (LOINC(r)) section names on 384 unique section headers from 362,311 operative notes. Overall, HL7-ON DSTU alone and HL7-ON DSTU with LOINC(r) section headers covered 66% and 79% of sections headers (93% and 98% of header instances), respectively. Section headers contained large numbers of synonyms, formatting variation, and variation of word forms, as well as smaller numbers of compound sections and issues with mismatches in header granularity. Robust operative note section mapping is important for clinical note interoperability and effective use of operative notes by natural language processing systems. The resulting operative note section resource is made publicly available. PMID- 26262167 TI - A Process for the Representation of openEHR ADL Archetypes in OWL Ontologies. AB - ADL is a formal language to express archetypes, independent of standards or domain. However, its specification is not precise enough in relation to the specialization and semantic of archetypes, presenting difficulties in implementation and a few available tools. Archetypes may be implemented using other languages such as XML or OWL, increasing integration with Semantic Web tools. Exchanging and transforming data can be better implemented with semantics oriented models, for example using OWL which is a language to define and instantiate Web ontologies defined by W3C. OWL permits defining significant, detailed, precise and consistent distinctions among classes, properties and relations by the user, ensuring the consistency of knowledge than using ADL techniques. This paper presents a process of an openEHR ADL archetypes representation in OWL ontologies. This process consists of ADL archetypes conversion in OWL ontologies and validation of OWL resultant ontologies using the mutation test. PMID- 26262168 TI - Harmonizing SNOMED CT with BioTopLite: An Exercise in Principled Ontology Alignment. AB - The integration of heterogeneous ontologies is often hampered by different upper level categories and relations. We report on an on-going effort to align clinical terminology/ontology SNOMED CT with the formal upper-level ontology BioTopLite. This alignment introduces several constraints at the OWL-DL level. The mapping was done manually by analysing formal and textual definitions. Descriptive logic classifiers interactively checked mapping steps, using small modules for increasing performance. We present an effective workflow, using modules of several scales. However, only part of the classes and relations could easily be mapped. The implications for future evolution of SNOMED CT are discussed. It seems generally feasible to use a highly constrained upper-level ontology as an upper level for the benefit of future SNOMED CT versions that are more interoperable with other biomedical ontologies. PMID- 26262169 TI - Standardized Cardiovascular Quality Assurance Forms with Multilingual Support, UMLS Coding and Medical Concept Analyses. AB - Standardized quality assurance (QA) plays an import role to maintain and develop success of cardiovascular procedures (CP). Well-established QA models from Germany could be shared in a form repository for world-wide reuse and exchange. Therefore, we collected the complete set of all quality QA forms for CP, which is obligatory to be filled out by all German health service providers. Original forms were converted into standardized study forms according to ODM (Operational Data Model) and translated into English. Common medical concepts and clusters of medical concepts were identified based on UMLS coding of form items. All forms are available on the web as multilingual ODM documents. UMLS concept coverage analysis indicates 88% coverage with few but critically important definition gaps, which need to be addressed by UMLS. PMID- 26262170 TI - vizHOME--A context-based home assessment: Preliminary implications for informatics. AB - The rapid migration of health care from the institution to the home presents a plethora of consumer health technology options.. The fit of these technologies to the users' actual task performance and environment remains to be explored. In the vizHOME study, we set out to conduct in-depth analyses of health information management tasks conducted by individuals residing in 20 homes in the Midwestern United States who self-reported with diabetes. This paper will explore early results from five of the 13 assessments we have performed to-date. Early observations are described and implications for informatics are posited. PMID- 26262171 TI - The Use of Applications in Distance Education Specialization Course as a Support Tool for Students Living in Remote Areas Without Internet. AB - The world is experiencing the popularization of mobile devices. This was made possible by the increasing technological advances and the advent of the Internet as a communication and information tool. These facts demonstrate that the development of applications compatible with such devices is an effective way to provide content to diverse audiences. In the educational field, these devices can be seen as technological support artifacts for distance education, serving as strategy for continuous and permanent education for health professionals. The Open University of Brazilian National Health System (UNA-SUS) offers distance learning courses, including specializating on free access. In order to increase the public reach, UNA-SUS developed mobile applications as supporting material for students. These applications can be accessed in offline mode, increasing the accessibility and therefore, improving the efficiency of the material. The 28 applications developed with responsive online books format currently reached the milestone of over 6,000 downloads. This number shows the positive acceptance of the format used, accentuated by the ease of having material downloaded from the device, not requiring the user to be connected to access content. PMID- 26262172 TI - An Architecture for Continuous Data Quality Monitoring in Medical Centers. AB - In the medical domain, data quality is very important. Since requirements and data change frequently, continuous and sustainable monitoring and improvement of data quality is necessary. Working together with managers of medical centers, we developed an architecture for a data quality monitoring system. The architecture enables domain experts to adapt the system during runtime to match their specifications using a built-in rule system. It also allows arbitrarily complex analyses to be integrated into the monitoring cycle. We evaluate our architecture by matching its components to the well-known data quality methodology TDQM. PMID- 26262173 TI - A Conceptual Framework for Decision-making Support in Uncertainty- and Risk-based Diagnosis of Rare Clinical Cases by Specialist Physicians. AB - Mitigating uncertainty and risks faced by specialist physicians in analysis of rare clinical cases is something desired by anyone who needs health services. The number of clinical cases never seen by these experts, with little documentation, may introduce errors in decision-making. Such errors negatively affect well-being of patients, increase procedure costs, rework, health insurance premiums, and impair the reputation of specialists and medical systems involved. In this context, IT and Clinical Decision Support Systems (CDSS) play a fundamental role, supporting decision-making process, making it more efficient and effective, reducing a number of avoidable medical errors and enhancing quality of treatment given to patients. An investigation has been initiated to look into characteristics and solution requirements of this problem, model it, propose a general solution in terms of a conceptual risk-based, automated framework to support rare-case medical diagnostics and validate it by means of case studies. A preliminary validation study of the proposed framework has been carried out by interviews conducted with experts who are practicing professionals, academics, and researchers in health care. This paper summarizes the investigation and its positive results. These results motivate continuation of research towards development of the conceptual framework and of a software tool that implements the proposed model. PMID- 26262174 TI - A Hybrid Approach Using Case-Based Reasoning and Rule-Based Reasoning to Support Cancer Diagnosis: A Pilot Study. AB - Recently there has been an increasing interest in applying information technology to support the diagnosis of diseases such as cancer. In this paper, we present a hybrid approach using case-based reasoning (CBR) and rule-based reasoning (RBR) to support cancer diagnosis. We used symptoms, signs, and personal information from patients as inputs to our model. To form specialized diagnoses, we used rules to define the input factors' importance according to the patient's characteristics. The model's output presents the probability of the patient having a type of cancer. To carry out this research, we had the approval of the ethics committee at Napoleao Laureano Hospital, in Joao Pessoa, Brazil. To define our model's cases, we collected real patient data at Napoleao Laureano Hospital. To define our model's rules and weights, we researched specialized literature and interviewed health professional. To validate our model, we used K-fold cross validation with the data collected at Napoleao Laureano Hospital. The results showed that our approach is an effective CBR system to diagnose cancer. PMID- 26262175 TI - Identifying Clinical Study Types from PubMed Metadata: The Active (Machine) Learning Approach. AB - We examined a process for automating the classification of articles in MEDLINE aimed at minimising manual effort without sacrificing accuracy. From 22,808 articles pertaining to 19 antidepressants, 1000 were randomly selected and manually labelled according to article type (including, randomised controlled trials, editorials, etc.). We applied a machine learning approach termed 'active learning', where the learner (machine) selects the order in which the user (human) labels examples. Via simulation, we determined the number of articles a user needed to label to produce a classifier with at least 95% recall and 90% precision in three scenarios related to evidence synthesis. We found that the active learning process reduced the number of training instances required by 70%, 19%, and 14% in the three scenarios. The results show that the active learning method may be used in some scenarios to produce accurate classifiers that meet the needs of evidence synthesis tasks and reduce manual effort. PMID- 26262177 TI - Characterization of Help Desk issues After the Implementation of an Emergency Department Electronic Health Record. AB - Electronic health records (EHRs) can produce significant disruption when first implemented. Successful implementations depend on the availability of technical and clinical support. We present a description of the frequency and types of issues raised during the first 12 months after the implementation of an EHR at a teaching hospital in Santiago, Chile. PMID- 26262178 TI - The e-NutriHS: a web-based system for a Brazilian cohort study. AB - The e-NutriHS is a web-based system developed to gather online information on health of a cohort of college students and graduates in nutrition. It consists of six validated and internationally recognized questionnaires regarding demographic and socioeconomic data, dietary habits, physical activity level, alcohol and tobacco use, anti-fat attitudes and personal and family histories. Our software and respective database is hosted in the School of Public Health server and is based on free programming languages. An e-NutriHS prototype was created preceding online deployment. An improved version of the website was released based on 20 volunteers' opinions. A total of 503 users were registered. Considering that web based systems produce reliable data, are easy to use, less costly and are less time-consuming, we conclude that our experience deserves to be shared, particularly with middle income economy countries. PMID- 26262179 TI - Problem Oriented Medical Record: Characterizing the Use of the Problem List at Hospital Italiano de Buenos Aires. AB - Problem oriented medical record (POMR) was born in late sixties. Expecting an ordered, complete and updated medical record were some of the goals of its founder. Several healthcare institutions have included problem list into their clinical records but some concerns have been reported. These concerns are in reference to their voluminosity, incompleteness and outdatedness. This study attempts to understand how healthcare professionals are using the problem list at Hospital Italiano de Buenos Aires (HIBA). We believe it is essential to understand the local reality applied to our own applications and cultural instances of documentation. This report is the basis from which several improvements could be made in order to meet the goals of Weed's proposal. PMID- 26262180 TI - Secretaries' role in EHR Documentation and the Implications of Establishing a Structured EHR System. AB - Secretaries play an important quality assurance role in today's medical record production. This study aimed to identify quality assurance tasks that a future system cannot easily compensate for when developing a new structured EHR in which the physicians do the writing themselves. The study identified two tasks, which we suggest should also be performed by secretaries in the future. PMID- 26262181 TI - Development of Markup Language for Medical Record Charting: A Charting Language. AB - Nowadays a lot of trials for collecting electronic medical records (EMRs) exist. However, structuring data format for EMR is an especially labour-intensive task for practitioners. Here we propose a new mark-up language for medical record charting (called Charting Language), which borrows useful properties from programming languages. Thus, with Charting Language, the text data described in dynamic situation can be easily used to extract information. PMID- 26262182 TI - Using Electronic Medical Record Data to Improve HIV Patient Monitoring, Clinical Decision-Making, and Quality Improvement: Lessons from Rwanda. AB - In developing countries, clinical guidelines and patient follow-up are primarily paper-based. We describe the use of Electronic Medical Record data for evidence based clinical decisions and improved HIV patients monitoring in rural Rwanda. PMID- 26262183 TI - Restructuring an EHR system and the Medical Markup Language (MML) standard to improve interoperability by archetype technology. AB - In 2001, we developed an EHR system for regional healthcare information inter exchange and to provide individual patient data to patients. This system was adopted in three regions in Japan. We also developed a Medical Markup Language (MML) standard for inter- and intra-hospital communications. The system was built on a legacy platform, however, and had not been appropriately maintained or updated to meet clinical requirements. To improve future maintenance costs, we reconstructed the EHR system using archetype technology on the Ruby on Rails platform, and generated MML equivalent forms from archetypes. The system was deployed as a cloud-based system for preliminary use as a regional EHR. The system now has the capability to catch up with new requirements, maintaining semantic interoperability with archetype technology. It is also more flexible than the legacy EHR system. PMID- 26262184 TI - Validation for Accuracy of Cancer Diagnosis in Electronic Medical Records Using a Text Mining Method. AB - To validate the accuracy of data in electronic medical record, we compared cancer diagnosis and key words in pathologic reports of cancer patients in a tertiary hospital, using text mining method. We investigated in fourteen kinds of cancers that had highest incidence rates in Korea. Approximately two-third (71.0%) of total patients had right match in cancer diagnosis with pathologic report. The ratio of concurrence was the highest (86.3%) in thyroid cancer patients, however, the ratio was the lowest (49.9%) in liver cancer patients. To prevent the errors in data input, a systematic alarm and feedback to clinicians should be required. PMID- 26262185 TI - Developing an Electronic Medical Record for Interlinked Care Services in Haiti. AB - A large clinical care and research organization in Haiti required an electronic medical record system (EMR) to serve the needs of its 30 interlinked clinical programs. After assessing available open source software, the local team designed and implemented a modular proprietary EMR that is improving data quality and patient care. Despite the many benefits of existing open source medical record systems, clinical centers with complex workflow patterns--even those in resource limited settings--should consider developing sustainable, local systems that fit their care model. PMID- 26262186 TI - Applicability of different types of Patient Records for Patient Recruitment Systems. AB - Patient records--types of Electronic Medical Records--are implemented to support patient recruitment. Different types of patient records have not yet been analyzed as to the number of Patient Recruitment System requirements can be found in each type of patient record. According to our analysis, personal electronic health records (PEHRs) tend to allow for most requirements to be found. PMID- 26262187 TI - Evaluating the data completeness in the Electronic Health Record after the Implementation of an Outpatient Electronic Health Record. AB - Electronic health records (EHRs) present an opportunity for quality improvement in health organitations, particularly at the primary health level. However, EHR implementation impacts clinical workflows, and physicians frequently prefer to document in a non-structured way, which ultimately hinders the ability to measure quality indicators. We present an assessment of data completeness-a key data quality indicator-during the first 12 months after the implementation of an EHR at a teaching outpatient center in Santiago, Chile. PMID- 26262188 TI - Health Information Needs for Child-in-Care. AB - When a child is taken into care the State is legally required to provide healthcare. Six forms were reviewed by medical care providers, foster parents and government social workers to understand their health information needs in caring and planning for child-in-care. The qualitative study used a sociotechnical systems framework and NVivo 10 for encoding. Interview findings include that the forms, if completed and available, meet most basic health information needs with additional forms used for complex health needs. The majority of participants indicate interest in electronic options. Focus groups will enable further study. PMID- 26262189 TI - Video Conferencing Services in Healthcare: One Communication Platform to Support All. AB - We present a novel approach to the design of video conferencing (VC) systems, taking advantage of recent technological achievements in web-based implementation. Delivering VC functionality as a service over the Internet opens new grounds for easier integration, support, and application in many scenarios, since hardware-agnostic ad-hoc VC connections are a feature of the proposed architecture. Validity is demonstrated through latency measures in surgical telementoring service and comparing them to reported thresholds. PMID- 26262190 TI - Implementation of a Teleconsultation Service in the Primary Health Care in Brazil. AB - The implementation of a Teleconsultation service in the primary health care is a great challenge. This work presents the effort made in the Espirito Santo Telehealth Project to consolidate the teleconsultation service. The impact of each strategy made was evaluated in terms of the number of teleconsultations produced. The combination of periodic visits and the promotion of local workshops were responsible for a sustainable use of the service for the last six months. PMID- 26262191 TI - Introducing Home Blood Pressure Telemonitoring for Children with Hypertension. AB - The goal of this study was to introduce home blood pressure (BP) telemonitoring in children with hypertension and to assess the feasibility of this approach. Acceptance of the system was assessed by attitudinal survey and semi-structured qualitative interview. Qualitative interview results showed consistently positive comments for content, interface and process components. BP measurements obtained by self-testing were as reliable as Dinamap measurements. The home telemonitoring system was positively accepted, easy to use and found to be helpful by participants. Home-based BP telemonitoring has significant potential to improve patient-centered delivery in children with hypertension. PMID- 26262192 TI - Providers Expectations on Telemedicine: A Qualitative Research in a Large Healthcare Network of Latin America. AB - The benefits of Telemedicine make it a viable, reliable and useful discipline for dispensing health care. This qualitative study is aimed to understand the expectations, opinions and previous knowledge of the professionals about telemedicine at the Hospital Italiano de Buenos Aires. RESULTS: Professionals realize that Telemedicine is inserted into their usual practice in an informal way. They consider telemedicine as an alternative to the traditional delivery of health care, but are afraid of their role in health care is undermined. Professionals point out very specific applications of Telemedicine such as monitoring the health of patients remotely, drug doses adjustments and sharing clinical information. CONCLUSION: Results suggest that professionals are not familiar with telemedicine and will be necessary to develop a training plan before implementation. PMID- 26262193 TI - Future Telehealth and Telecare Reference Design based on IoT Technologies: From Remote Monitoring to Smart Collaborative Services with Decision Support. AB - The demographic changes are producing aging societies across the world, resulting in greater demands on the health and care systems due to age-related disabilities and chronic diseases. Efficient telehealth and telecare services are needed to control the corresponding expenditures, by supporting increased collaboration between different professional and involving informal health care providers, and by empowering the patients to manage their health and well-being. Emerging trial systems for remote patient monitoring present preliminary solutions not exempt of certain limitations. We propose a future eHealth reference system architecture and core components, aiming at secure, smarter and more collaborative telehealth and telecare services. The implicit cooperation between the so-far separated domains of consumer well-being services and public telehealth and telecare services will be beneficial for all parties. PMID- 26262194 TI - The EU-project United4Health: User-Centred Design and Evaluation of a Collaborative Information System for a Norwegian Telehealth Service. AB - This study presents the user-centred design and evaluation process of a Collaborative Information System (CIS), developed for a new telehealth service for remote monitoring of chronic obstructive pulmonary disease patients after hospital discharge. The CIS was designed based on the information gathered in a workshop, where target end-users described the context of use, a telehealth workflow and their preferred ways of interaction with the solution. Evaluation of the iterative refinements were made through user tests, semi-structured interviews and a questionnaire. A field trial reported results on the ease of use and user satisfaction during the interaction with the fully developed system. The implemented CIS was successfully deployed within the secured Norwegian Health Network. The research was a result of cooperation between international partners within the EU FP7 project United4Health. PMID- 26262195 TI - Enhancing tele-collaboration Networks by Patient Participation. AB - This paper decribes an approach for extending tele-collaboration to the patient and allowing the patient's participation by accessing and providing data and thereby keeping the responsibilty for maintaining a personal health record with the patient. The approach has been implemented and is in use with the nationwide tele-collaboration network TKmed. PMID- 26262196 TI - The Effect of Mobile App Follow-up Care on the Number of In-person Visits Following Ambulatory Surgery: A Randomized Control Trial. AB - Women's College Hospital (WCH) in Toronto offers specialized ambulatory surgical procedures. A feasibility study using a mobile appliciation (app) to supplement in-person follow-up care after surgery suggests that the mobile app adequately detects postoperative complications, eliminates the need for in-person follow-up care and is cost-effective. This is concordant with other postoperative telemedicine studies. The purpose of this study is to determine if we can avert in-person follow-up care through the use of mobile app compared to conventional, in-person follow-up care in the first month following surgery amongst breast reconstruction patients at WCH. This will be a pragmatic, single-centre, open, controlled, 2-arm parallel-group superiority randomized trial. Mobile app follow up care is a novel approach to managing patients postoperatively with the potential to avert in-person follow-up and generate cost-savings for the healthcare system and patient. PMID- 26262197 TI - Impact of a mobile health aplication in the nursing care plan compliance of a home care service in Belo Horizonte, Minas Gerais, Brazil. AB - OBJECTIVE: To assess impact of a mobile health solution in the nursing care plan compliance of a home care service. METHODS: A retrospective cohort study was performed with 3,036 patients. Compliance rates before and after the implementation were compared. RESULTS: After the implementation of a mobile health aplication, compliance with the nursing care plan increased from 53% to 94%. The system reduced IT spending, increased the nursing team efficiency and prevented planned hiring. CONCLUSION: The use of a mobile health solution with geolocating feature by a nursing home care team increased compliance to the care plan. PMID- 26262198 TI - Augmented Reality: Real-Time Information Concerning Medication Consumed by a Patient. AB - This paper describes a mobile prototype capable of recognizing characters from a photograph of a medication package. The prototype was built to work on the iOS platform and was developed using Objective-C and C programming languages. The prototype, capable of recognizing text out of an image, included image processing algorithms, text processing algorithms, and techniques to search and handle information from a database. This prototype is presented as an option for capturing reliable and validated information by using new technologies available to the general population. PMID- 26262199 TI - Description of a Mobile-based Electronic Informed Consent System Development. AB - Seoul National University Hospital constructed and implemented a computer-based informed consent system in December 2011. As of 2013, 30% of the informed consents were still filled out manually on paper. Patients and medical staff continuously suggested the implementation of a system for electronic informed consent using portable devices. Therefore, a mobile-based system for electronic informed consent was developed in 2013 to prevent the issues that arise with computer-based systems and paper informed consent. The rate of filling out electronic informed consent increased from 69% to 95% following the implementation of the mobile-based electronic informed consent. This construction of a mobile-based electronic informed consent system would be a good reference point for the development of a mobile-based Electronic Medical Record and for various mobile system environments in medical institutions. PMID- 26262200 TI - Exploring the Challenges and Opportunities of eHealth Tools for Patients with Sickle Cell Disease. AB - Sickle cell disease (SCD) is the most prevalent inherited blood disorder in the world. The symptoms decrease the quality of life of patients and can cause premature death. Self-help solutions for chronic patients are rising and increase the quality of life of patients. We are interested to identify the usefulness of eHealth tools for patients with SCD. We did a literature review to identify the main problems faced by patients and the existing eHealth solutions. The results show a low number of studies in the field but a multi-disciplinary interest. Positive health benefits for patients are reported as well as the need for more research. Patients and caregivers lack of education about the disease, healthy behaviors are unknown and clinical best practices underused. E-health tools can offer an appropriate support for the self-management of SCD by improving the quality of life of patients, by enhancing patient health literacy and by allowing clinicians to make better decisions. PMID- 26262201 TI - Development and Usability Evaluation of the Mobile Delirium Assessment App Based on Confusion Assessment Method for Intensive Care Unit (CAM-ICU). AB - Delirium is a common complication among patients in ICU settings. The accuracy of using the assessment tool CAM-ICU to detect delirium is relatively low during routine practice among bedside nurses. The aim of this study is to develop a mobile application (app) to detect delirium in early stage and to test its usability among ICU nurses. The app was developed with Java and installed on a mobile device. A questionnaire was created based on the Technology Acceptance Model (TAM) measuring their response to the four domains of TAM: perceived usefulness (PU), perceived ease of use (PEOU), attitudes towards usage (ATU) and behavioral intention to use (BIU). One hundred and two ICU nurses completed the survey. The result indicated that the app we developed has easy to use interfaces and is easier to use compared to the regular CAM-ICU. PMID- 26262202 TI - Viability of a Bioelectrical Signal Acquisition System Energized by Cellphone with NFC. AB - Currently, smartphones are used in various systems in the medical field due to the presence of various features, notably Near Field Communication (NFC). NFC utilizes communication technology and an energy supply based on electromagnetic induction. One of the most common medical tests is the electrocardiogram (ECG), through which various heart diseases can be diagnosed. The objective of this study is to evaluate the feasibility of providing power to a bioelectrical signal acquisition module using a mobile phone with NFC. After testing it was indicated that it is possible to construct a passive module to acquire ECG signals using NFC mobile phone. PMID- 26262203 TI - Smart Glasses--A New Tool in Medicine. AB - Smart glasses, defined as a computerized communicator with a transparent screen and a video camera, wearable as a pair of glasses, have started to be tested for a variety of health related applications. This poster reviews some of the early experiences and gives a series of proposals for possible uses in medicine with a particular emphasis on medical education. PMID- 26262204 TI - Access Control for Mobile Assessment Systems Using ID. AB - The assessment of shelters during disaster is critical to ensure the health of evacuees and prevent pandemic. In the Ishinomaki area, one of the areas most damaged by the Great East Japan Earthquake, the highly organized assessment helped to successfully manage a total of 328 shelters with a total of 46,480 evacuees. The input and analysis of vast amounts of data was tedious work for staff members. However, a web-based assessment system that utilized mobile devices was thought to decrease workload and standardize the evaluation form. The necessary access of information should be controlled in order to maintain individuals' privacy. We successfully developed an access control system using IDs. By utilizing a unique numerical ID, users can access the input form or assessment table. This avoids unnecessary queries to the server, resulting in a quick response and easy availability, even with poor internet connection. PMID- 26262205 TI - Using mobile devices to improve the safety of medication administration processes. AB - Within preventable medical errors, those related to medications are frequent in every stage of the prescribing cycle. Nursing is responsible for maintaining each patients safety and care quality. Moreover, nurses are the last people who can detect an error in medication before its administration. Medication administration is one of the riskiest tasks in nursing. The use of information and communication technologies is related to a decrease in these errors. Including mobile devices related to 2D code reading of patients and medication will decrease the possibility of error when preparing and administering medication by nurses. A cross-platform software (iOS and Android) was developed to ensure the five Rights of the medication administration process (patient, medication, dose, route and schedule). Deployment in November showed 39% use. PMID- 26262206 TI - Study of Development for RFID System to Hospital Environment. AB - RFID/USN develops information systems for anytime, anywhere to anybody access Electronic Medical Records (EMR). The goal of the present study is to develop a RFID/USN-based information system for the hospital environment. First, unable to recognize, second, able to recognize as a pursuit of place and suppose the time of medical examination. A retrospective analysis of 235 RFID monitoring results, from four ENT ambulatory clinics of Seoul National University Hospital were extracted by a reader program and monitoring of RFID tag (2006.11.16~2006.12.16). RFID detection for sensing reader of this study has been put into representing "place" and "spending time" of patients for medical history taking and examination. Through the RFID of detection for specific place and spending time of medical examination, RFID/USN develops information system progressing in the EMR of hospital system. PMID- 26262207 TI - Developing an Online Decision Aid for Osteoarthritis. AB - A decision aid for osteoarthritis was developed using the best available evidence on effect size, potential harms and self-rated performance for other attributes. The aid was developed using a multi-criteria decision analytic tool capable of combing evidence and an individual's preferences for the attributes related to treatment. PMID- 26262208 TI - An electronic device to record consensual reflex in human pupil. AB - Examination of the pupil offers an objective evaluation of visual function as well as the vegetative pathways to the eye. This work proposes the development of an effective method and a portable device to test the consensual pupillary reflex. The first results demonstrate the success of a new device construction and methodology to record the consensual reflex with different stimulus, in a situation of complete blockage of light. PMID- 26262209 TI - A Global Analysis of Approaches to Sharing Clinical Data with Patients. AB - Engaging patients in their care has become a topic of increasing importance, and enabling patients to have access to their clinical data is a key aspect of such engagement. To investigate on an international scale the current state of approaches for providing patients with access to their own clinical information, individuals from 16 countries, across six continents, participated in cross sectional semi-structured interviews. Interview questions focused on social and cultural influences that affected patient engagement activities, government support for current and planned initiatives, data ownership models, and technical issues. Substantive initiatives for providing information to patients in the majority of countries interviewed are present; however, these initiatives were diverse in nature and stage of implementation. Efforts to improve patient access to data are active on a global-scale. There are many open questions about best practices and much can be learned by adopting an international perspective to guide future implementation efforts. PMID- 26262210 TI - Is Access to eHealth Records Important for Patients?--Opinions of Healthcare Personnel. AB - Sweden has had significant progress with the the introduction of electronic health records. A pilot county deployed in an eHealth service in 2012, giving access to health records for all of its patients. This eHealth service is, however, a controversial issue. Two surveys were conducted to discover whether healthcare professionals' opinions differ between professionals, and between staff who have had experience with patients using eHealth records and those, to date, who have had none. Experienced nurses found this eHealth service more important for the patients compared to unexperienced nurses outside the pilot county, as well as both semi-experienced physicians. PMID- 26262211 TI - Rolling Medical Practice: Ambulant Mobile Medical Care for Rural Areas. AB - We designed, constructed, and evaluated a mobile medical care vehicle called "Rollende Arztpraxis" (rolling medical practice, RMP) that delivers the full medical care of a general practitioner to increase medical care supply in rural areas. Six communities have been identified, where the RMP has been visited 501 times in 14 months. Two different schedules of stops and treatment times have been tested. We show that the RMP treated mainly elderly and multimorbid patients. An accompanying study showed high acceptance and satisfaction of treated patients and treating doctors. An economic evaluation of three different utilization models with three treatment modes each showed no financial sustainability. We show that ambulatory care in rural areas can be complemented by a mobile care unit, if legal and financial barriers can be overcome. PMID- 26262212 TI - Online Communication and Chronic Obstructive Pulmonary Disease (COPD). AB - This is an explorative and qualitative study that examines a municipal's rehabilitation program "Online Viva" (2014-2015). The questions are whether "Online Viva" improves the citizens' participatory health and whether it prevents exacerbation of COPD. "Online Viva" includes respiratory training and district nursing consultancy for elderly people with COPD. The district nurses' presence in the citizens' homes is replaced by online communication. The study involves 9 citizens and 5 health professionals. Preliminary results show that online consultations and training prevent anxiety, exacerbation, and support the citizens' management of COPD. The citizens find that the "Online Viva" reduces their need for hospitalization, and this is confirmed by the district nurses. Furthermore, the citizens find that their specific needs are fulfilled, making them comfortable in managing their COPD. It is emphasized by the citizens and the district nurses that they must have been in personal contact with each other before they meet online. Furthermore, it must be possible to visit the citizens in their private homes in addition to an online contact, if needed. PMID- 26262213 TI - Development and practice of ISMS at a Radiotherapy Hospital by using IHE Integration profiles. AB - Our hospital is specialized for radiation therapy and has many information devices. Various job categories are working. When we implemented an EMR, we aimed to enforce ISMS by using IHE profiles. To solve the already existed system related problems, we selected and use some profiles (EUA, PSA, ATNA and PAM). After implementation, we audited and then some findings were pointed out. These findings are being settled by the PDCA cycle. We also found that appropriate IHE profiles were effective in the building of ISMS. PMID- 26262214 TI - Optimizing Safety, Fidelity and Usability of an Intelligent Clinical Support Tool (ICST) For Acute Hospital Care: an Australian Case Study Using a Multi-Method Delphi Process. AB - This research focuses on a major health priority for Australia by addressing existing gaps in the implementation of nursing informatics solutions in healthcare. It serves to inform the successful deployment of IT solutions designed to support patient-centered, frontline acute healthcare delivery by multidisciplinary care teams. The outcomes can guide future evaluations of the contribution of IT solutions to the efficiency, safety and quality of care delivery in acute hospital settings. PMID- 26262215 TI - An Integrated Workflow For Secondary Use of Patient Data for Clinical Research. AB - This work proposes an integrated workflow for secondary use of medical data to serve feasibility studies, and the prescreening and monitoring of research studies. All research issues are initially addressed by the Clinical Research Office through a research portal and subsequently redirected to relevant experts in the determined field of concentration. For secondary use of data, the workflow is then based on the clinical data warehouse of the hospital. A datamart with potentially eligible research candidates is constructed. Datamarts can either produce aggregated data, de-identified data, or identified data, according to the kind of study being treated. In conclusion, integrating the secondary use of data process into a general research workflow allows visibility of information technologies and improves the accessability of clinical data. PMID- 26262216 TI - Screening Mammography Efficacy: A Comparison Between Screen-Film, Computed Radiography and Digital Mammography in Taiwan. AB - Breast cancer screening has been proven effective in Western countries, and our National Health Bureau also started to offer free screening mammography for women aged between 50 and 69, since July 2004. This study aims to compare the efficacy between distinctive mammography screening modalities. Prompting the assessment of digital screening in the radiological sciences, we provide insight into the practical informatics application of such tools. PMID- 26262217 TI - Evaluation of a Cyber Security System for Hospital Network. AB - Most of the cyber security systems use simulated data in evaluating their detection capabilities. The proposed cyber security system utilizes real hospital network connections. It uses a probabilistic data mining algorithm to detect anomalous events and takes appropriate response in real-time. On an evaluation using real-world hospital network data consisting of incoming network connections collected for a 24-hour period, the proposed system detected 15 unusual connections which were undetected by a commercial intrusion prevention system for the same network connections. Evaluation of the proposed system shows a potential to secure protected patient health information on a hospital network. PMID- 26262218 TI - Design and development of an EMR for Ebola Treatment Centers in Sierra Leone using OpenMRS. AB - Ebola treatment presents unique challenges for medical records because strict infection control requirements rule out most conventional record-keeping systems. We used the OpenMRS platform to rapidly develop an EMR system for the recently opened Kerry Town, Sierra Leone Ebola Treatment Centre. This system addresses the need for recording patient data and communicating it between the infectious and non-infectious zones, and is specifically designed for maximum usability by staff wearing cumbersome protective equipment. This platform is interoperable with other key eHealth systems in the country, and is extensible to other sites and diseases. PMID- 26262219 TI - The Impact of an Electronic Medical Record on Repeat Laboratory Test Ordering Across Four Australian Hospitals. AB - In this study we examined the impact of an Electronic Medical Record (EMR) on repeat test rates (i.e., the same test ordered within a specified window of time) for a commonly ordered set of laboratory tests; Electrolytes, Urea, Creatinine [EUC], Full Blood Counts [FBC] and Liver Function Tests [LFT]. The results point to the potential that timely, evidence-based electronic decision support features can have on the efficiency and effectiveness of the pathology laboratory process and its contribution to quality patient care. PMID- 26262220 TI - Implementation of Data Drive Heart Rate and Respiratory Rate parameters on a Pediatric Acute Care Unit. AB - The majority of hospital physiologic monitor alarms are not clinically actionable and contribute to alarm fatigue. In 2014, The Joint Commission declared alarm safety as a National Patient Safety Goal and urged prompt action by hospitals to mitigate the issue [1]. It has been demonstrated that vital signs in hospitalized children are quite different from currently accepted reference ranges [2]. Implementation of data-driven, age stratified vital sign parameters (Table 1) for alarms in this patient population could reduce alarm frequency. PMID- 26262221 TI - Application of Barcoding to Reduce Error of Patient Identification and to Increase Patient's Information Confidentiality of Test Tube Labelling in a Psychiatric Teaching Hospital. AB - Learning from the experience of another medical center in Taiwan, Kaohsiung Municipal Kai-Suan Psychiatric Hospital has changed the nursing informatics system step by step in the past year and a half . We considered ethics in the original idea of implementing barcodes on the test tube labels to process the identification of the psychiatric patients. The main aims of this project are to maintain the confidential information and to transport the sample effectively. The primary nurses had been using different work sheets for this project to ensure the acceptance of the new barcode system. In the past two years the errors in the blood testing process were as high as 11,000 in 14,000 events per year, resulting in wastage of resources. The actions taken by the nurses and the new barcode system implementation can improve the clinical nursing care quality, safety of the patients, and efficiency, while decreasing the cost due to the human error. PMID- 26262222 TI - Open Source Software For Patient Data Management In Critical Care. AB - We have previously developed a Patient Data Management System for Intensive Care based on Open Source Software. The aim of this work was to adapt this software to use in Emergency Departments in low resource environments. The new software includes facilities for utilization of the South African Triage Scale and prediction of mortality based on independent predictive factors derived from data from the Tabarre Emergency Trauma Center in Port au Prince, Haiti. PMID- 26262223 TI - Measuring ICTs Adoption in Health Care Facilities in Uruguay. AB - The use of Information and Communication Technologies (ICTs) has gained an important role to enhance healthcare systems by increasing access to services, and improving the quality and equity of care. In order to evaluate the stage of ICTs adoption in the Uruguayan healthcare system, the Governmental Salud.uy Program carried out a national survey to establish the baseline for ICTs adoption, as well as define a set of indicators so as to evaluate the progress on this topic. Data was recorded following the OECD methodology. PMID- 26262224 TI - Syntactic and Semantic Errors in Radiology Reports Associated With Speech Recognition Software. AB - Speech recognition software (SRS) has many benefits, but also increases the frequency of errors in radiology reports, which could impact patient care. As part of a quality control project, 13 trained medical transcriptionists proofread 213,977 SRS-generated signed reports from 147 different radiologists over a 40 month time interval. Errors were classified as "material" if they were believed to alter interpretation of the report. "Immaterial" errors were subclassified as intrusion/omission or spelling errors. The proportion of errors and error type were compared among individual radiologists, imaging subspecialty, and time periods using .2 analysis and multiple logistic regression, as appropriate. 20,759 (9.7%) reports contained errors; 3,992 (1.9%) contained material errors. Among immaterial errors, spelling errors were more common than intrusion/omission errors (P<.001). Error proportion varied significantly among radiologists and between imaging subspecialties (P<.001). Errors were more common in cross sectional reports (vs. plain radiography) (OR, 3.72), reports reinterpreting results of outside examinations (vs. in-house) (OR, 1.55), and procedural studies (vs. diagnostic) (OR, 1.91) (all P<.001). Dictation microphone upgrade did not affect error rate (P=.06). Error rate decreased over time (P<.001). PMID- 26262225 TI - Diagnostic Imaging Integrated Network: A Teleradiology Pilot in Public Hospitals in Uruguay. AB - A network of health care centers allows radiologists to share diagnostic images in different areas of Uruguay. This solution is based on an informatics multicenter application for center management, enabling the creation, storage and distribution of images and reports from different imaging modalities according to outsourcing agreements. The solution improves health care territorial equity and reduces asymmetry in resources distribution. PMID- 26262226 TI - First Step to Big Data Research in Hospital. AB - Hospitals have accumulated large amounts of data driven by hospital information system such as EMR, PACS, CPOE, and LIMS. While most data are stored in hospital systems, researchers have still experienced trouble to use clinical data. To overcome this problem and promote "big data" research, clinical research information system is necessary. Here an example of such a system, ABLE (Asan BiomedicaL research Environment), will be introduced. PMID- 26262227 TI - Implementing Georeferencing in the Decision-Making Process of a Health Care Provider in Uruguay. AB - Proper management of information is not only essential but also critical in any organization's decision making process. Data integration and spacial visualization are the key features of georeferencial systems, which bring support to decision making in epidemiology as well as sanitary planning.This paper shows the development of a georeferential system that interacts with the data provided by the Health Care System.Thereby allowing creation of viable methods which will help to improve patient care, treatments, and interventions through building space-time relationships. PMID- 26262228 TI - A Development of Automatic Audit System for Written Informed Consent using Machine Learning. AB - In Japan, most of all the university and advanced hospitals have implemented both electronic order entry systems and electronic charting. In addition, all medical records are subjected to inspector audit for quality assurance. The record of informed consent (IC) is very important as this provides evidence of consent from the patient or patient's family and health care provider. Therefore, we developed an automatic audit system for a hospital information system (HIS) that is able to evaluate IC automatically using machine learning. PMID- 26262229 TI - Service Quality: A Main Determinant Factor for Health Information System Success in Low-resource Settings. AB - With the increasing implementation of different health information systems in developing countries, there is a growing need to measure the main determinants of their success. The results of this evaluation study on the determinants of HIS success in five low resource setting hospitals show that service quality is the main determinant factor for information system success in those kind of settings. PMID- 26262230 TI - Taming the Data Quality Dragon--A Theory and Method for Data Quality by Design. AB - A lack of data quality (DQ) is often a significant inhibitor impeding the realization of cost and quality benefits expected from Clinical Information Systems (CIS). Attaining and sustaining DQ in CIS has been a multi-faceted and elusive goal. The current literature on DQ in health informatics mainly consists of empirical studies and practitioners' reports, but often lack a holistic approach to addressing DQ 'by design'. This paper seeks to present a general framework for clinical DQ, which blends foundational engineering theories with concepts and methods from health informatics. We define an architectural viewpoint for designing and reasoning about DQ. We introduce the notion of DQ Probes for monitoring and assuring DQ during system operation. The concepts presented have been validated in a real-world case study. PMID- 26262231 TI - A Medical Image Backup Architecture Based on a NoSQL Database and Cloud Computing Services. AB - The use of digital systems for storing medical images generates a huge volume of data. Digital images are commonly stored and managed on a Picture Archiving and Communication System (PACS), under the DICOM standard. However, PACS is limited because it is strongly dependent on the server's physical space. Alternatively, Cloud Computing arises as an extensive, low cost, and reconfigurable resource. However, medical images contain patient information that can not be made available in a public cloud. Therefore, a mechanism to anonymize these images is needed. This poster presents a solution for this issue by taking digital images from PACS, converting the information contained in each image file to a NoSQL database, and using cloud computing to store digital images. PMID- 26262232 TI - Digital Imaging and Electronic Data Capture in Multi-Center Clinical Trials. AB - While medical image data is managed in picture archiving and communication systems (PACS) via the digital imaging and communications in medicine (DICOM) protocol, electronic data capture systems (EDCS) in clinical trials lack PACS interfacing. This complicates the trial workflow and increases errors, time, and costs. In this work, four system architectures of image integration for multi center trials are analyzed with respect to data, function, visual, and context integration levels. We propose an open source-based architecture composed of OpenClinica, DCM4CHE, and Weasis for EDCS, PACS, and Viewer, respectively. PMID- 26262233 TI - An Exponential Increase in Regional Health Information Exchange With Collaborative Policies and Technologies. AB - In the United States, the ability to securely exchange health information between organization has been limited by technical interoperability, patient identity matching, and variable institutional policies. Here, we examine the regional experience in a national health information exchange network by examining clinical data sharing between eleven Northern California organizations using the same health information exchange (HIE) platform between 2013-2014. We identify key policies and technologies that have led to a dramatic increase in health information exchange. PMID- 26262234 TI - Towards Standardized Patient Data Exchange: Integrating a FHIR Based API for the Open Medical Record System. AB - Interoperability is essential to address limitations caused by the ad hoc implementation of clinical information systems and the distributed nature of modern medical care. The HL7 V2 and V3 standards have played a significant role in ensuring interoperability for healthcare. FHIR is a next generation standard created to address fundamental limitations in HL7 V2 and V3. FHIR is particularly relevant to OpenMRS, an Open Source Medical Record System widely used across emerging economies. FHIR has the potential to allow OpenMRS to move away from a bespoke, application specific API to a standards based API. We describe efforts to design and implement a FHIR based API for the OpenMRS platform. Lessons learned from this effort were used to define long term plans to transition from the legacy OpenMRS API to a FHIR based API that greatly reduces the learning curve for developers and helps enhance adhernce to standards. PMID- 26262235 TI - Development of Clinical Database System Specialized for Heavy Particle Therapy. AB - We have developed a data archiving system for study of charged particle therapy. We required a data-relation mechanism between electronic medical record system (EMR) and database system, because it needs to ensure the information consistency. This paper presents the investigation results of these techniques. The standards in the medical informatics field that we focus on are Integrating the Healthcare Enterprise (IHE) and 2) Health Level-7 (HL7) to archive the data. As a main cooperation function, we adapt 2 integration profiles of IHE as follows, 1) Patient Administration Management (PAM) Profile of IHE-ITI domain for patient demographic information reconciliation, 2) Enterprise Schedule Integration(ESI) profile of IHE-Radiation Oncology domain for order management between EMR and treatment management system(TMS). We also use HL7 Ver2.5 messages for exchanging the follow-up data and result of laboratory test. In the future, by implementation of this system cooperation, we will be able to ensure interoperability in the event of the EMR update. PMID- 26262236 TI - Interoperable Archetypes With a Three Folded Terminology Governance. AB - The use of openEHR archetypes increases the interoperability of clinical terminology, and in doing so improves upon the availability of clinical terminology for both primary and secondary purposes. Where clinical terminology is employed in the EPR system, research reports conflicting a results for the use of structuring and standardization as measurements of success. In order to elucidate this concept, this paper focuses on the effort to establish a national repository for openEHR based archetypes in Norway where clinical terminology could be included with benefit for interoperability three folded. PMID- 26262237 TI - Standardization of Information about Birth in the Obstetric Discharge Summary. AB - Clinical information about the birth composes an important set of data to the documentation about the care provided during childbirth. Formalized in the document Obstetric Impatient Discharge Summary (OIDS), such information are essential for continuity of mother and child attention, in the health care network. The main paper's objective is to propose an Information Model for this document based on ISO Standard 13606 for interoperability between health information systems in Minas Gerais, Brazil. PMID- 26262238 TI - Hospitalization Discharge Summary: Standardization of Information Model. AB - Brazil has a long tradition in the use of health information systems, however- until now--there is no consensus on the minimum data set from which to compose discharge summaries. This article describes the methodology used by a group of experts--members of WG1 of ISOTC 215 Health Informatics Brazilian mirror committee--to define the information model of the discharge summary. This paper describes the current status of the standardization process and the first pilot tests with this infomation content. PMID- 26262239 TI - The Challenge of e-Health Presence on a Petroleum Platform: Using Telemedicine to Make Operation of Pre-Salt Wells a Reality. AB - Telemedicine can be defined as the use of electronic media for the transmission of clinical data and information from one location to another using information technology and telecommunication in order to provide immediate clinical health care at long distances. This new approach can involve specialized medical service centers in the oil production at great distances from the offshore installations in Brazil. The importance of the right health diagnosis, taken at the proper time, will make a serious difference in the facilities, which will be located around 300 km offshore. This paper presents an overview of telemedicine and its different applications, comparing them according to level of maturity and applicability. Important results from a case study in a fixed oil platform are analyzed. At the end of this work, the strategy of telemedicine implementation in a Brazilian petroleum operator is discussed. PMID- 26262240 TI - Archetype Development Process of Electronic Health Record of Minas Gerais. AB - The Electronic Health Record (EHR) supports health systems and aims to reduce fragmentation, which will enable continuity of patient care. The paper's main objective is to define the steps, roles and artifacts for an archetype development process (ADP) for the EHR at the Brazilian National Health System (SUS) in the State of Minas Gerais (MG). This study was conducted using qualitative analysis based upon an applied case. It had an exploratory purpose metodologically defined in four stages: literature review; descriptive comparison; proposition of an archetype development process and proof of concept. The proof of concept showed that the proposed ADP ensures the archetype quality and supports the semantic interoperability in SUS to improve clinical safety and the continuity of patient care. PMID- 26262241 TI - Unanticipated consequences of hospital-based insulin management order sets. AB - Recent studies demonstrated risks to patient safety associated with implementation of electronic applications for medication management in ambulatory care. This study was aimed at demonstrating similar phenomenon in a hospital setting. After introduction of computerized order set targeting hypoglycemia, the frequency of hypoglycemia significantly decreased from 1/1/07 to 12/31/08. In contrast, the frequency of hyperglycemia increased at the same time from 1/1/07 to 12/31/07. Only after subsequent introduction of a hospital-wide standardized insulin order set including hyperglycemia policies frequency of hyperglycemic episodes declined. Hypo/hyperglycemia is associated with adverse clinical outcomes in the inpatient setting. Retroactive analysis showed that if hypoglycemic and hyperglycemic policies were introduced simultaneously, unexpected increase in frequency of hyperglycemic episodes could have been avoided. These data are informative in identifying unanticipated consequences of an insulin management order sets focused entirely on hypoglycemia. A balanced approach in implementing insulin management guidelines concurrently addressing both hypoglycemia and hyperglycemia policies is warranted. PMID- 26262242 TI - The Impact of Implementing a New Computerized Physician Order Entry (CPOE) System on Pharmaceutical Interventions in a Tertiary Brazilian Hospital. AB - We analyzed trends in pharmaceutical interventions during the implementation of a new computerized physician order entry (CPOE) process in a tertiary hospital in Brazil. The new process utilized an eletronic interface that was designed in house and an automatic order extension program. The new process reduced the number of order transcriptions and mitigated other potential CPOE-related errors [1]. PMID- 26262243 TI - Methodology to Establish Associations between Data and Clinical Assessment for Computerized Nursing Process in Intensive Care Units. AB - Combining the Information and Communication Technologies (ICT) in the Nursing Process (NP) is a way to support their development in health contexts. The alliance between ICT and the NP integrates and organizes a logical structure of data and clinical information supporting nurses in decision-making. This manuscript describes the methodology used to articulate data and information cynical of Computerized Nursing Process (CNP), according to ICNP(r) 2.0, associating detailed clinical assessment of each human system to their diagnoses, interventions, and patient outcomes. This is a methodological study and technological production conducted in 2010, and is developed in three stages. It was possible to restructure the CNP from the associations between the data and clinical information of all human systems (cardiovascular, neurological, respiratory, renal, gastrointestinal, cutaneous, musculoskeletal, female/male and biopsychosocial) to their diagnoses, interventions, and results of Nursing. PMID- 26262244 TI - Nursing Software for Emergency Triage (NSET). AB - Determining the priority of attention in an Emergency Room (ER) has always been a difficult issue. Priority is determined with a simple triage system as people arrive at the hospital. It is important to establish how long they can wait for treatment. In order to obtain the best assessment of patients' conditions, we built a Nursing Software for Emergency Triage (NSET). The objective of this work was to assess the efficacy of the NSET versus the triage process without any software (TWS). Results showed that the NSET we built was a substantial help. With this software, we decreased significantly:1) the length of the triage system process, 2) the waiting time of patients in the waiting room, 3) the number of complaints and 4) the number of patients who walk away. In conclusion, the NSET improves and helps to define more accurately a patient's risk. NSET helps in the emergency department triage. PMID- 26262245 TI - Nursing Clinical Documentation System Structured on NANDA-I, NOC, and NIC Classification Systems. AB - Information is a key feature that health professionals need to exercise their profession with efficiency and quality. This study aims to present the experience of the usage of an electronic system for clinical documentation in nursing in a university hospital. It is a methodological research of technology production. The system was developed in four phases: Conception, Elaboration, Construction, and Transition, and was named Electronic Documentation System of the University of Sao Paulo Nursing Process (PROCEnf-USPTM). The knowledge base of PROCEnf-USPTM was organized in hierarchy of domains and classes, according to NNN linkages. PMID- 26262246 TI - A Trial of Nursing Cost Accounting using Nursing Practice Data on a Hospital Information System. AB - Hospital administration is very important and many hospitals carry out activity based costing under comprehensive medicine. However, nursing cost is unclear, because nursing practice is expanding both quantitatively and qualitatively and it is difficult to grasp all nursing practices, and nursing cost is calculated in many cases comprehensively. On the other hand, a nursing information system (NIS) is implemented in many hospitals in Japan and we are beginning to get nursing practical data. In this paper, we propose a nursing cost accounting model and we simulate a cost by nursing contribution using NIS data. PMID- 26262247 TI - An Electronic Nursing Patient Care Plan Helps in Clinical Decision Support. AB - Information technology can help to improve health care delivery. The utilisation of informatics principle enhances the quality of nursing practices through improved communication, documentation and efficiency. The Nursing Profession constitutes 34% of the total workforce in the Hong Kong Hospital Authority (HA) and includes 21,000 nurses in 2012. To enhance the quality of care and patient safety in both hospitals and community care setting, it is essential that an integrated electronic decision support system for nurses is designed to track documentation and support care or service including observations, decisions, actions and outcomes throughout the care process at each point-of-care. The Patient Care Plan project was set up to achieve these objectives. The Project adheres to strict documentation information architecture to ensure data sharing is freely available. Preliminary results showed very promising improvement in clinical care. PMID- 26262248 TI - Clinical Decision Support to Implement CYP2D6 Drug-Gene Interaction. AB - The level of CYP2D6 metabolic activity can be predicted by pharmacogenomic testing, and concomitant use of clinical decision support has the potential to prevent adverse effects from those drugs metabolized by this enzyme. Our initial findings after implementation of clinical decision support alerts integrated in the electronic health records suggest high feasibility, but also identify important challenges. PMID- 26262249 TI - A Scalable Architecture for Rule Engine Based Clinical Decision Support Systems. AB - Clinical Decision Support systems (CDSS) have reached a fair level of sophistication and have emerged as the popular system of choice for their aid in clinical decision making. These decision support systems are based on rule engines navigate through a repertoire of clinical rules and multitudes of facts to assist a clinical expert to decide on the set of actuations in response to a medical situation. In this paper, we present the design of a scalable architecture for a rule engine based clinical decision system. PMID- 26262250 TI - Clinical Decision Support Based on Integrated Patient Models: A Vision. AB - Clinical decision making is non-trivial given the amounts of data and knowledge that needs to be considered. So far, medical knowledge, biological knowledge and patient data are separated from each other and need to be integrated mentally by a physician to form an overarching patient model. In this paper, we describe a vision for future decision support systems that link knowledge about organ functions, biological processes, treatment decisions and clinical data represented in repsective models. Requirements and challenges for realizing this vision will be collected. PMID- 26262251 TI - Impact of Specific Alerts in Potassium-Increasing Drug-Drug Interactions. AB - Alerts in potassium(K+)-increasing drug-drug interactions (DDIs) are often ignored due to their low specificity. Although different approaches have been implemented to address DDIs, subsequent clinical studies revealed poor adherence to such alerts. We therefore suggest a novel alert concept currently being evaluated in a randomized clinical trial in a large teaching hospital. Highly specific reminders (to monitor K+) and alerts (of hyperkalaemia) are displayed to the physicians of the intervention group, whereas reminders and alerts are suppressed in the control group. Preliminary analysis shows a high alert specificity. Furthermore, the physicians of the intervention group reacted significantly faster to a problematic situation arising during a K+-increasing DDI compared to the physicians of the control group, indicating that this concept has an impact on physician behaviour. PMID- 26262252 TI - Detecting, Monitoring, and Reporting Possible Adverse Drug Events Using an Arden Syntax-based Rule Engine. AB - The detection of adverse drug events (ADEs) is an important aspect of improving patient safety. The iMedication system employs predefined triggers associated with significant events in a patient's clinical data to automatically detect possible ADEs. We defined four clinically relevant conditions: hyperkalemia, hyponatremia, renal failure, and over-anticoagulation. These are some of the most relevant ADEs in internal medical and geriatric wards. For each patient, ADE risk scores for all four situations are calculated, compared against a threshold, and judged to be monitored, or reported. A ward-based cockpit view summarizes the results. PMID- 26262253 TI - Systems Medicine for Multiple Myeloma: A Review on Decision Support Systems. AB - Systems medicine is a current approach trying to improve treatment for patients with complex diseases by analyzing as much phenotype and genotype data as possible for the disease in question. For individualized treatment decisions in clinical practice, this task has to be supported by an application system with decision support component. For a research project on systems medicine we reviewed methods for decision support. Criteria for selecting a method are derived from characteristics of the data and the diseases. They include, among others: dimensionality of data and existence of a priori models for diseases. As a result we decided to implement a prototype system with a case-based reasoning component for systems medicine on multiple myeloma. PMID- 26262254 TI - Bridging the Gap between Clinical Practice Guidelines and Archetype-Based Electronic Health Records: A Novel Model Proposal. AB - The lack of a unique, standardized format for representing data and knowledge is one of the existing difficulties to integrating decision support into Electronic Health Records (EHRs). OBJECTIVE: Propose an archetype-based model to allow the integration of Clinical Practice Guidelines (CPG) and EHRs; design and implement this proposed model. RESULTS: A generic model was designed for the integration of CPG into EHRs, and an archetype-based EHR for Chronic Kidney Disease Prevention based on rules from CPGs, was made as a proof of concept of this novel integration. PMID- 26262255 TI - Virtual Oncological Networks--IT Support for an Evidence-based, Oncological Health Care Management. AB - An interdisciplinary and intersectoral coordinated therapy management along Clinical Practice Guidelines can ensure that all patients receive adequate diagnostic, treatment, and supportive services that lead most likely to optimal outcomes. Within the research project "Virtual Oncological Networks", guideline compliant pathways are defined and enacted within a Health Care Management Platform to support treatment planning and ongoing care of oncological diseases. PMID- 26262256 TI - Computer-Interpretable Clinical Guidelines: A Review and Analysis of Evaluation Criteria for Authoring Methods. AB - There are a variety of authoring tools and methods for producing computer interpretable clinical guideline (CIG). This work is a review of the evaluation of tools and methods currently in use to author CIGs. The aim of this paper is to present the results of a literature review on the evaluation criteria. Both controlled database search and a subsequent snowballing were used to identify relevant literature. The evaluation criteria and evaluation methods of CIG related themes were manually identified in the found literature. Based on the 32 relevant papers found, 68 evaluation criteria were identified which were then classified into ten themes. We identified the most and least frequently mentioned areas of concern in evaluation which indicate areas that have been neglected in system evaluation. PMID- 26262257 TI - Internal domain-specific language based on Arden Syntax and FHIR. AB - We demonstrate the concept of Arden Syntax, which is like Domain Specific Language (DSL), for describing decision support rules that take advantage of modern programming language concepts. Using object relational mapper and meta programming enables the conceptualization of FHIR resources from various data sources, and reduces the complexity of knowledge retrieval in decision rules. PMID- 26262258 TI - Computationally Comparing and Analyzing All Published Scoring Systems for Diagnosis of Disseminated Intravascular Coagulation. AB - The clinical literature presents four different scoring systems (SS) for the diagnosis of disseminated intravascular coagulation (DIC) by four institutions: ISTH, JMHLW, JAAM and KSTH. In this study a Java program was written to retrieve medical records from the MIMIC-II database and apply the criteria of all four. The program then quantified the agreement of each DIC SS with each other and demonstrated notorious dissent. Furthermore, the average internal composition of each score was also quantified. All source code produced is available for download at https://github.com/fabkury/hedicim. PMID- 26262259 TI - Precedent Approach to Decision Making in Clinical Processes. AB - This poster describes the results of promising research in the field of clinical processes management and decision making support. The authors formulated common scientific problems connected with the modelling of treatment processes. The research is supported by grants from the Ministry of Education and Science of the Russian Federation (the project RFMEFI60714X0089). PMID- 26262260 TI - Semantic Interoperability in Clinical Decision Support Systems: A Systematic Review. AB - The interoperability of Clinical Decision Support (CDS) systems with other health information systems has become one of the main limitations to their broad adoption. Semantic interoperability must be granted in order to share CDS modules across different health information systems. Currently, numerous standards for different purposes are available to enable the interoperability of CDS systems. We performed a literature review to identify and provide an overview of the available standards that enable CDS interoperability in the areas of clinical information, decision logic, terminology, and web service interfaces. PMID- 26262261 TI - Development of a Mobile System Decision-support for Medical Diagnosis of Asthma in Primary Healthcare--InteliMED. AB - The structure of public and primary healthcare in Brazil is organized in a way to provide decentralized services. In theory, this scenario could enable the usage of mobile devices integrated with information systems of several purposes. In addition, there is a need of decision-support tools that are based on collected evidences, once the professional of primary healthcare, which essentially has general knowledge (non-specialist). Therefore there is a need of information that support the decision-making process on more specific contexts. This paper presents the proposal, experience of development and application of the InteliMED, a decision-support system to asthma diagnosis of children and adolescents through decision-trees and mobile devices (smartphones and tablets). PMID- 26262262 TI - Using Discrete Event Simulation to predict KPI's at a Projected Emergency Room. AB - Discrete Event Simulation (DES) is a powerful factor in the design of clinical facilities. DES enables facilities to be built or adapted to achieve the expected Key Performance Indicators (KPI's) such as average waiting times according to acuity, average stay times and others. Our computational model was built and validated using expert judgment and supporting statistical data. One scenario studied resulted in a 50% decrease in the average cycle time of patients compared to the original model, mainly by modifying the patient's attention model. PMID- 26262263 TI - Clinical Decision Support Using Electronic Medical Records: For the Improvement of Diabetes Care and Proper Use of Insulin for Inpatients. AB - The aim of the study is to develop a scheme of a decision support system concerning insulin intervention for inpatients. Transaction data for 32,637 inpatients were collected from the EMR. As a result, antidiabetic agents were not taken by 38.9%-41.7% of patients with a Disease Complicated by DM. It is recommended that the EMR should provide a suggestion about insulin level for diseases with DM as a complicating factor. PMID- 26262264 TI - Why should I?--Acceptance of Health Information Technology Among health professionals. AB - Applying the Technology Acceptance Model, the end user intentions to use technology applications is studied. The study finds the end users negative perception of the usefulness of the application as a major factor in its suboptimal utilisation. PMID- 26262265 TI - Diffusion of innovation: Telehealth for care at home. AB - The 'care at home' study focused on a Scottish telehealth service, which was designed to support children with palliative and complex care needs. Using the diffusion of innovation theory, this poster highlights the differences between the way telehealth is used in the public sector and in a third sector or a voluntary organization. Analysis of the data, taken from interviews with key stakeholders, illuminate barriers and solutions as noted by clinicians who see the clear benefits and potential risks of telehealth use at home. In conclusion, it is argued that a strategic steer towards a culture of innovation is needed to support effective use of telehealth in clinical practice. Senior managers in the National Health Service in the United Kingdom need to 'unleash' the goodwill of staff who are eager to exploit innovation in clinical practice. PMID- 26262266 TI - Visualizing Sensor Data through an Open Platform for Connected Devices. AB - Integrating sensor systems within the home can be a tedious process due to the challenges of deploying systems across multiple environments, customizing applications, and connecting across various devices. We demonstrate the deployment of sensors using the Lab of Things platform within a residence over a 3 month period. We developed a real time visualization application from the generated sensor data, and evaluated it through a survey with 19 older adults and caregivers. Findings can be a valuable guide to scale a study across multiple settings, and to create personalized interfaces. PMID- 26262267 TI - Automated Evaluation of Medical Software Usage: Algorithm and Statistical Analyses. AB - Evaluating the correctness of medical software usage is critically important in healthcare system management. Turf [1] is a software that can effectively collect interactions between user and computer. In this paper, we propose an algorithm to compare the recorded human-computer interaction events with a predefined path. Based on the pass/fail results, statistical analysis methods are proposed for two applications: to identify training effects and to compare products of the same functionality. PMID- 26262268 TI - Study of Screen Design Principles for Visualizing Medical Records. AB - To improve UX of EMR/EHR, the screen design principles for the visualization are required. Through the study of common attributes of medical records, we present four principles and show three screen designs by applying them. PMID- 26262269 TI - User-centered design to develop clinical applications. Literature review. AB - User-centered design is mentioned by Norman as "the need for a design that uses the natural properties of the individuals, exploiting the relationships and constraints and focusing on the needs and interests of the user, in order to make the final products usable and understandable". This is also important in health developments. The objective of this paper is to search and analyze articles in the healthcare field where user-centered design principles have been applied. We describe findings in this topic from articles published between January 1995 and September 2014. PMID- 26262270 TI - A Model for Usability Evaluation for the Development and Implementation of Consumer eHealth Interventions. AB - Consumer eHealth products are often used by people in their own homes or other settings without dedicated clinical supervision, and often with minimal training and limited support--much as eCommerce and eGovernment applications are currently deployed. Internet based self-care systems have been advocated for over a decade as a way to reduce costs and allow more convenient care, and--because of the expectation that they will be used to reduced health cost--, by increasing self care and avoiding hospitalization. However, the history of consumer eHealth interventions is mixed, with many unsuccessful implementations. Many consumer eHealth products will form part of a broader complex intervention, with many possible benefits and effects on both individuals and society. This poster describes a model of consumer eHealth assessment based on multiple methods of usability evaluation at different stages in the design and fielding of eHealth systems. We argue that different methods of usability evaluation are able to give valuable insights into the likely effects of an intervention in a way that is congruent with software development processes. PMID- 26262271 TI - Usability Analysis Of A Customized Documentation System For Nurse Population Health Managers. AB - The University of Missouri's population health management pilot employs 22 Nurse Care Managers (NCM) to manage medical casework for approximately 10,000 patients. We studied the NCMs' documentation system to identify interruptions to their clinical workflow, and identify missing functionality. We used an interview script and Morae software to observe and record five NCMs at work, measuring time on task, click counts, and task completion. We also documented quantitative and qualitative responses to a directed interview. All tasks were completed satisfactorily, with completion times of 443+/-275 seconds and click counts of 58+/-23. Surveys on a scale of 1 (worst) to 5 (best) scored "ease of use" at 3.4+/-1.1, "integration of functions" at 3.0+/-1.2, and "ease of learning" at 2.6+/-1.5. Overall, the system is functional and reliable but could be improved to support workflow. PMID- 26262272 TI - Digital Inclusion for Older Adults based on Physical Activities: an Age Concern. AB - Nowadays, we are living in an interdependent and interconnected world during an age that is driven by technological progress. It has extraordinary potential to improve the quality of later life: creating social networks to tackle isolation and loneliness; transforming services to help people live independently at home for longer; empowering consumers; and enabling civil participation. In light of this, this poster aims to present the development process of a digital booklet for mobile devices--smartphones and tablets that illustrate the benefits of doing physical exercises for older adults aiming to improve life quality and minimizing digital exclusion. PMID- 26262273 TI - Development of the eHealth Literacy Assessment Toolkit, eHLA. AB - In a world with rising focus on the use of eHealth, the match between the competences of the individual and the demands of eHealth systems becomes increasingly important, thus making assessment of eHealth literacy as a measure of user competences a vital element. We propose the eHealth Literacy Assessment toolkit, eHLA, evaluating the user by seven scales: computer familiarity, confidence, incentive and performance as well as functional health literacy, health literacy self-assessment and health literacy performance, as a first step toward development of technology that accommodates the literacy level of the user. PMID- 26262274 TI - Type 1 Diabetes in Twitter: Who All Listen To? AB - Knowing what the conversation on Twitter regarding type 1 diabetes (T1D) is about can help in understanding the kind of information relevant to the individuals affected by the disease. The profile of Twitter users posting on T1D was collected and classified. The number of re-tweets was also registered. The tweets posted by non-governmental organizations (NGOs), communication media, and individuals affected by T1D had higher number of potential readers. More than a half of the tweets were posted by individuals affected by T1D, and their tweets were the most re-tweeted. The next most active users were NGOs and healthcare professionals. However, while tweets soliciting for research funds posted by the NGOs were the next most re-tweeted messages, tweets posted by healthcare professionals were the least re-tweeted. Twitter could be used more actively by healthcare professionals to disseminate correct information about T1D. PMID- 26262275 TI - Characterizing Consumer Health Informatics in Low and Middle Income Countries. AB - Consumer Health Informatics (ConsHI) involves patients in health care through ICT, with Low and Middle Income Countries recently entering the field. Compelling successes and complete failures call for the identification of success factors. Of 1092 automatically retrieved articles, 85 were classified as ConsHI. Their service characteristics and the economic and societal factors of the countries of origin were classified. Descriptive statistics were applied in the search for clusters of features that together appear as driving factors. Most factors (financial endowment, number of languages spoken etc) showed no or paradoxical effects. Societal maturity and low population density appear as enabling factors. PMID- 26262276 TI - 3D CPR Game Can Improve CPR Skill Retention. AB - Adequate cardiopulmonary resuscitation (CPR) skill is essential in improving survival rate of sudden cardiac arrest (SCA). However, the skill deteriorates rapidly following CPR training. We developed a computer game by using 3 Dimensional virtual technology (3-D CPR game) for laypersons in the purpose to improve skill retention. As the testing phase, a randomized control trial, in which we recruited 97 freshman medical students who had no prior CPR training experience, was used to test its effect on 3-month CPR Skill retention. The usability of the game was also tested using a 33 item questionnaire rated with 5 point Likert scale. Three months after the initial CPR training, the retention rate of CPR skill in the game group was significantly higher compared with the control (p<0.05) and the average score on 4 dimensions of usability were 3.99 4.05. Overall, using 3-D CPR game in improving CPR skill retention is feasible and effective. PMID- 26262277 TI - Improvement of Hemoglobin with Repeated Health Checks Among Women in Bangladesh. AB - The residents of several cities and villages in Bangladesh underwent e-health checkups. The distribution of Hb increased from the first hemoglobin (Hb) measurement to the second, and some women recovered from severe anemia. A strong effect was observed in subjects who were prescribed iron supplements. The mean blood pressure improved after the first health examination, and the blood sugar level increased. In countries with shortages of health practitioners and health care providers, e-health examinations and instructions may be useful interventions because they make people health conscious and improve their health status. PMID- 26262278 TI - Cardiac auscultation simulator embedded in virtual learning environment to support medical teaching. AB - Heart auscultation remains as an important clinical tool in heart disease diagnostics. A prototype was developed, using an existing database of clinical and cardiac sounds of pregnant women [1]. The context for virtual learning is cardiac disease during pregnancy (Partum and Post Partum situations). Based on real histories, cardiac sounds, and complementary exams, this pilot presents the most frequent diagnosis of cardiac diseases during pregnancy. PMID- 26262279 TI - Global Challenges in People-Centered E-Health. AB - People-centered health care seeks an active role for the patient while empowering all other members of the health care team. By promoting greater patient responsibility and optimal usage, patient-centered health care leads to improved health outcomes, quality of life and optimal value for health care investment. This paper reviews some definitions of people-centered health care and various e health approaches around the world used to implement this vision. The barriers and enablers to implementation this type of approach are explored. This paper provides a proposed research agenda for future implementations of people-centered e-health. PMID- 26262280 TI - Use of Patient Portals: Personal Health Information Management in Older Adults. AB - The personal health information management (PHIM) of older adults is poorly understood. We describe initial results from the SOARING (Studying Older Adults & Researching Information Needs and Goals) study at the University of Washington, a participatory design investigation of PHIM in older adults. We conducted in-depth interviews with older adults (n=71) living in a variety of residential settings. A surprising 21% of participants reported using patient portals. Another 17% of participants reported prior use or anticipated use of portals in the future. We identified preferences and needs as well as barriers and facilitators to portal use. Our findings indicate that patient portals designed to target the specific needs for older adults can suport PHIM. We offer recommendations for expanded research. PMID- 26262281 TI - Machine Assisted Translation of Health Materials to Chinese: An Initial Evaluation. AB - There is an unmet need for Chinese language health materials in the USA. We investigated the use of machine translation (MT) plus human post-editing (PE) to produce Chinese translations of public health materials. We collected 60 documents that had been manually translated from English to traditional Chinese. The English versions were translated to Chinese using MT and assessed for errors and time required to correct via PE. Results suggest poor initial translation may explain the lack of quality translations despite PE. PMID- 26262282 TI - Lessons Learnt from Evaluation of Computer Interpretable Clinical Guidelines Tools and Methods: Literature Review. AB - Representation of clinical guidelines in a computer interpretable format is an active area of research. Various methods and tools have been proposed which have been evaluated based on different evaluation criteria. The evaluation results in the literature and their lessons learnt can be a valuable learning resource in order to redesign and improve the tools. Therefore, this research investigates the lessons learnt from the evaluation studies. Broad search in literature together with a purposeful snowball method were performed to identify the related papers that report any type of evaluation or comparison. We reviewed and analysed the lessons learnt from the evaluation results and classified them into 17 themes which reflect the suggestion concerns. The results indicate that the lessons learnt are more focused on tool functionalities, integration, sharing and maintenance domain. We provide suggestions for the area which had less attention. PMID- 26262283 TI - The need for cost-benefit analyses of eHealth in low and middle-income countries. AB - Cost and benefit analyses are crucial for eHealth interventions, especially in low and middle income countries (LMIC). We performed a scoping review, with goals to acquire an overview of cost-benefit studies and to collect indicators that are being used for costs and savings with respect to eHealth. Of all retrieved articles, 29 were included in our analysis and 21 contained cost/savings indicators which we categorized into outcome measures with respect to providers, patients and other stakeholders. Nearly all authors stated that more evidence from economic analyses by health economists are urgently needed and that pilot projects should collect cost related data for evaluation. PMID- 26262284 TI - Effects of electronic prescription on pharmacy productivity. AB - Electronic prescriptions affect pharmacy workflows. In this study, we measure the workflow efficiency in pharmacies in 2006 and 2012: both, in traditional workflow when electronic prescription was not in use, and in new direct delivery workflow, which is the mandated workflow model in the case of electronic prescriptions. PMID- 26262285 TI - (Br-SCMM) Brazilian Smart City Maturity Model: A Perspective from the Health Domain. AB - The term definition "Smart City" still allows various interpretations, and this causes some difficulty in establishing parameters to measure how smart the cities can be. This paper presents a Maturity Model that uses a set of minimum domains and indicators that aim to encourage cities of different sizes to identify their potential and improve processes and public policies. PMID- 26262286 TI - Factors Influencing Consent for Electronic Data Linkage in Urban Latinos. AB - Within the context of patient participation in a Learning Health System, this study examined consent rates and factors associated with consent for linking survey data with electronic clinical data in a sample of 2,271 Latinos. Consent rate was 96.3%. Government insurance status and health literacy significantly influenced the odds of consent. PMID- 26262287 TI - Communication problems between end-users and technicians through a Help Desk in a Health Information System. AB - Communication between users and technicians is crucial for improving Help Desk performance. The objective of this study is to know and understand perceptions, and needs of users and help desk technicians. A qualitative study based on interviews was performed. The emergent topics were communication, workload and misperceptions between end-users and technicians. There are false perceptions between them that affect their interaction and work dynamics. PMID- 26262288 TI - Speech therapy teleconsultations of a public telehealth service in a developing country. AB - Our aim is to assess speech therapy teleconsultations performed by the Telehealth Network of Minas Gerais, a public telehealth service that attends 722 cities in Brazil, to demonstrate the importance of the telehealth to support these professionals. In this observational retrospective study, consecutive speech therapy teleconsultations performed by the Telehealth Network of Minas Gerais, Brazil, from February 2011 to May 2014, were analyzed. Socio-demographic characteristics of the cities which requested teleconsultations were assessed, and teleconsultations were analyzed based on the type of query. Throughout the study, 259 valid speech therapy teleconsultations were performed. There were no significant differences in socio-demographic characteristics of municipalities that requested and did not request speech therapy teleconsultations. Speech therapists (65%), nurses (27%) and physicians (5%) requested the highest number of teleconsultations, mostly related to the area of language (47%), oral motor skills (29%), voice (20%), audiology (18%) and dysphagia (10%). In conclusion, teleconsultations demonstrated to be a potential tool for speech therapists working in remote areas. PMID- 26262289 TI - Teleconsultations to Provide Support for Primary Care Practitioners and Improve Quality of care--the Experience of a Large Scale Telehealth Service in Brazil. AB - This observational restrospective study was designed to assess teleconsultations performed by a public telehealth service in Brazil. A satisfaction survey was used to assess the impact on clinical practice. A total of 63,975 teleconsultations were performed, from April 2007 to November 2014. Family physicians (33%) and dermatologists (19%) answered most queries. From January to February 2014 (n=895), the most frequent queries were about etiology (30%) and pharmacological treatment (25%). The satisfaction survey in 2014 (n=571) showed that teleconsultations avoided patient referal in 78%. This study aims to shows the potential of telehealth to provide support to primary care practitioners in remote cities. PMID- 26262290 TI - Clinical Quality Control of a Large-Scale Teleconsultation Service. AB - The Telehealth Network of Minas Gerais (TNMG) is a public telehealth service in Brazil that assists 722 municipalities in the state of Minas Gerais. As a large scale teleconsultation service, it was important to implement clinical quality control to guarantee the quality of the service. Our aim is to describe the audit of the teleconsultation responses performed by TNMG. A random sample was selected from teleconsultations performed by the specialists from the TNMG between January and February 2014. The responses were evaluated regarding size, objectivity, quality, ethics, courtesy and grammar. A total of 640 teleconsultation responses were assessed, and the mean scores were >=2.45. Objectivity and quality had the lowest scores in the different specialities. The methodology was useful for evaluating the teleconsultation service and for identifying the areas to improve. PMID- 26262291 TI - Audit of primary care electrocardiograms sent as emergency to a telehealth service - the Telehealth Network of Minas Gerais, Brazil. AB - The Telehealth Network of Minas Gerais (TNMG) is a public telehealth service in Brazil that has performed electrocardiogram (ECG) analysis since 2005. From February to March 2014, 28% of ECGs were classified as "emergency" by the primary care tele-health sites. This quasi-experimental study aimed to investigate the reasons behind the high number of emergency ECGs being sent in, the implementation of corrective actions, and an assessment of the impact of these actions. In the 1st phase, primary care units that sent >70% of ECGs as emergency from February to March 2014 were selected. The 2nd phase consisted of the intervention. In the 3rd phase, the proportion of ECGs sent as an emergency during the 1st and 2nd months post intervention were assessed. Of the 63 cities selected during the 1st phase, 50% of the practitioners did not know the proper definition of emergency. After the intervention, 67% of the cities had a significant reduction in the proportion of ECGs sent as an emergency during the 1st month, and 17% had a significant reduction during the 2nd month. PMID- 26262292 TI - Referring Quality Assessment of Primary Health Care for Endocrinology in Rio Grande do Sul, Brazil. AB - This paper presents results of an assessment of the quality research of endocrinology referrals in the public health system in the state of Rio Grande do Sul. From the analysis of 4,458 requests for endocrinology referrals, it was found that 15% of referrals had insufficient information for evaluation and 71% showed no clinical justification for authorization of referencing. The partial results of the study indicated that the lack of information makes it impossible to clinically regulate these requests. The use of referencing protocols associated with telemedicine tools can assist doctors in primary health care in the clinical management and make access to specialized services more equitable and timely. PMID- 26262293 TI - 2,000,000 Electrocardiograms by Distance: An Outstanding Achievement for Telehealth in Brazil. AB - Our aim is to describe the evolution of the telediagnostic service of the Telehealth Network of Minas Gerais (TNMG), a public telehealth service in Brazil. It started in 2006 with 82 cities, restricted to electrocardiography analysis. Currently it extends to 772 cities--performing also Holter, ambulatory blood pressure monitoring and retinography analysis--and 48 ambulances in the north of the state, as part of a myocardial infarction system of care. Using low-cost equipment and simple technology, TNMG has employed various strategies to increase telehealth use. The number of ECGs performed by TNMG has progressively increased. It was expected to achieve 2 million in February 2015. The utilization rates were around 90%. It proved to be economically sound, promoting savings of 45M USD for an investment of 10.2M USD. It is currently a regular health service in the state, integrated into the healthcare system. In conclusion, the telehealth model developed in Minas Gerais produced good clinical and economical results. PMID- 26262294 TI - Care Professionals' Perceived Usefulness Of A Rehabilitation Ehealth Service In Stroke Care. AB - Despite many attempts to support stroke patients, there is still room for improvement. The aim of this study is to gain insight into care professionals' perceived usefulness of an online care and rehabilitation planning tool. A functional prototype was developed and presented to a neurology team in a primary care centre in Stockholm. Three focus group meetings were conducted. The data were analysed based on the unified theory of acceptance and use of technology. The results indicate that the care professionals were positive towards the tool and described potential usefulness such as ease of understanding the rehabilitation process and support for collaboration among care providers and also cooperation between the patient and the team. They also identified challenges such as time limitation in daily care. PMID- 26262295 TI - Routine Health Information Systems in South Africa--Opportunities for Improvement. AB - A recurring theme in published studies is the need for the appropriate human and other resources to support routine health information system (RHIS) implementation. While training in the use of specific RHIS and the availability of the required resources for implementation are essential for all users, other factors such as managers' understanding of the role of RHIS in supporting health services; the ability to interpret RHIS data; and a focus on data quality are further requirements for effective RHIS implementation. PMID- 26262296 TI - Perceived Reasons for High and Low Quality Observational HIV Research Data. AB - Audits of data quality in a Latin America HIV research network revealed that study sites collected weight measurements, laboratory results, and medication data of inconsistent quality. We surveyed site personnel about perceived drivers of their high or low quality data. Most sites reported their research teams contained no data specialists and that missing data stemmed primarily from incomplete patient assessments at the point of care rather than inconsistent data recording. The root causes of data errors resulted from limited clinic resources (e.g., broken scales, limited record storage space), workflow complications, or the indifference of external participants towards research activities. Understanding these factors supports targeted quality improvement processes. PMID- 26262297 TI - Telehealth in Brazil: Contemporary Tool for Access to Health. AB - This work raises questions about telehealth in Brazil, especially the areas of diagnosis, treatment and monitoring at distance, emphasizing its importance for the improvement of health conditions. It was based on a literature review. Three successful experiences were selected as examples: The Minas Gerais Project Telecardio, the Sao Paulo University Teleaudiology and Telerehabilitiation of UnB. Despite the increase of telehealth experiences in Brazil, much remains to be done in regard to diagnosis, treatment and follow-up, with potential positive effects on health. PMID- 26262298 TI - Stigma and On-line Health Information Seeking of U.S. South Asian Cancer Survivors. AB - The internet has replaced physicians as primary health information source for cancer-survivors.It is important to uncover barriers/facilitators to cancer information seeking, particularly on-line.Asian Americans are the fastest growing U.S racial/ethnic minority, 2) cancer is the leading cause of r death and 3) cancer knowledge is low among them and little research is done on their cancer information seeking strategies. This study aims to examine qualitatively cancer information-seeking patterns of the Asian American group, South Asians, using in depth interview methods. Family members and social networks are highly engaged in providing informational support to South Asian cancer survivors. such collaborative information seeking is limited by stigma related to cancer and must be taken into consideration when developing culturally appropriate cancer health information seeking interventions in such communities. PMID- 26262299 TI - End-User Experiences and Expectations Regarding Data Registration and Reuse Before the Implementation of a (New) Electronic Health Record: A Case Study in Two University Hospitals. AB - Patient data stored in Electronic Health Records (EHRs) are used during care provision but are also potentially usefully reused for other purposes. Data (re)use requires good data quality, which necessitates efforts by healthcare professionals for proper data registration. However, their commitment depends on their perception of the reuse benefits. We developed a questionnaire to investigate the perception and expectations of end-users on data registration and reuse in two university hospitals starting a joint EHR implementation. Especially personnel in direct patient care reports to spend much time (40%) on data registration and this group is not willing to spend more time with the new EHR. Additionally, approximately one third of the personnel did not yet have a clear view on future developments regarding data registration and reuse. We found only small differences between hospitals. PMID- 26262300 TI - Quality of Life Measurements in Spinal Cord Injury Patients. AB - We recently developed UceWeb, an application for direct elicitation of utility coefficients (UCs), i.e. a measure of health states quality perceived by patients. UceWeb was used to interview a sample of patients affected by spinal cord injury (SCI). A standard questionnaire for measuring quality of life (QoL) and another one for the system evaluation were also administered to the same patients. The aims of this work are to (i) evaluate UceWeb usability; (ii) investigate relationships among QoL values elicited with different methods, (iii) create a reference set of UCs for the health states experienced by SCI patients. We show preliminary results obtained with the first 20 patients. Despite great variability found among QoL values elicited with the different methods, interesting correlations with patients' condition and profile have been found. PMID- 26262301 TI - A Methodology for Adapting Psychoeducational Content to Mobile Platforms. AB - Studies show that current modes of psychoeducation (PE) cannot be availed of by a substantial population of those in need. Mobile health technologies have great potential to serve such populations. However converting PE to mobile platforms is challenging. We present a methodology for this purpose based on existing learning styles theory, and developed PE apps successfully, using it. CONCLUSION: Useful PE apps can be developed easily using the proposed method. PMID- 26262302 TI - Special People in Routine Health Information Systems Implementation in South Africa. AB - An analysis of roles and decision making structures to facilitate routine health information system (RHIS) implementation and use in public health facilities in South Africa identified a wide range of stakeholders in these processes. Two broad categories of RHIS 'special people' are analysed, i.e. leaders (administrative and/or clinical) and bridgers/support staff. In addition to health system personnel with specific responsibility for RHIS, users with an interest in effective use of RHIS and RHIS outputs, and staff of external system and/or service providers, can play significant roles in RHIS implementation and use. PMID- 26262303 TI - Emergency Department Information System Education and Training for Clinicians: Lessons Learned. AB - Of all the potential barriers to a successful Electronic Health Record (EHR) adoption, the importance of training is often underestimated, potentially jeopardizing the implementation. Following best practices recommendations, we designed and implemented a comprehensive EHR training framework. The aim of this poster is to describe our experience with such a framework in the implementation of our home-grown Emergency Department Information System (EDIS), report lessons learned and provide recommendations for other institutions facing EHR adoptions in Chile and Latin America. PMID- 26262304 TI - The Role of the IT Department in Information System and Organizational Redesign. AB - This paper is based on a qualitative study of IT organization and clinical practice over a period of 3 years supported by additional data during the last 2 years. This paper argues that redesign is central to understanding and developing both healthcare information systems and organizations. The importance of the IT organization is also stressed throughout this paper as a pertinent partner and power when considering organizational change and learning in hospitals as it can serve both as a barrier and a catalyst of change and flexibility in the organization through information systems management. Therefore it is important to consider and secure appropriate forms for redesign and learning in cooperation with the IT department. PMID- 26262305 TI - Developing an Open-Source Bibliometric Ranking Website Using Google Scholar Citation Profiles for Researchers in the Field of Biomedical Informatics. AB - We developed the Biomedical Informatics Researchers ranking website (rank.informatics-review.com) to overcome many of the limitations of previous scientific productivity ranking strategies. The website is composed of four key components that work together to create an automatically updating ranking website: (1) list of biomedical informatics researchers, (2) Google Scholar scraper, (3) display page, and (4) updater. The site has been useful to other groups in evaluating researchers, such as tenure and promotions committees in interpreting the various citation statistics reported by candidates. Creation of the Biomedical Informatics Researchers ranking website highlights the vast differences in scholarly productivity among members of the biomedical informatics research community. PMID- 26262306 TI - Proposal for a European Public Health Research Infrastructure for Sharing of health and Medical administrative data (PHRIMA). AB - In Europe, health and medical administrative data is increasingly accumulating on a national level. Looking further than re-use of this data on a national level, sharing health and medical administrative data would enable large-scale analyses and European-level public health projects. There is currently no research infrastructure for this type of sharing. The PHRIMA consortium proposes to realise the Public Health Research Infrastructure for Sharing of health and Medical Administrative data (PHRIMA) which will enable and facilitate the efficient and secure sharing of healthcare data. PMID- 26262307 TI - Towards a Tool for Malaria Supply Chain Management Improvement in Rural Ghana. AB - The maintenance of adequate quantities of antimalarial medicines and rapid diagnostic tests (RDTs) at health facilities in rural areas of sub-Saharan Africa is a challenging task because of poor supply chain management. Antimalarial stock outs in the communities could lead patients (that need to travel long distances to get medications) to remain untreated, develop severe malaria and die. A prototype to improve the management of health commodities in rural Ghana through the visualization of current stock levels and the forecasting of commodities is proposed. PMID- 26262308 TI - Health Interoperability into Practice: Results of the Development of a Consent Form in a Pilot Project in a Health District in Sao Paulo, Brazil. AB - Interoperability of health information systems is a centerpiece of the "E-Health" Brazilian Ministry of Health strategy. It aims to solve at least partially the health information technology puzzle that we face today. This paper describes a health information exchange pilot project in a health district of the city of Sao Paulo. It discusses the results of the development of an informed consent form for health information exchange. This consent form showed excellent results, with median application time of 3 minutes and with 97.8% of patients feeling fully clarified. The patients' perception when faced with options of consent to share their data is also described. PMID- 26262309 TI - Healthcare in Disasters and the Role of RFID. AB - Disasters either natural or man-made are inevitable, and therefore disaster management has always been an important function of government. Since during a disaster healthcare is often adversely affected, a lot of effort has been made in terms of researching effective responses and ways of improving the quality of delivered care to direct casualties and the rest of the community. In this regard, information technology plays an important role to help healthcare systems achieve this goal. One of these technologies that has become popular recently is Radio-Frequency Identification (RFID). This paper explores the relationship between emergency management and disaster healthcare and examines the role of RFID. It is suggested that RFID will become an integral part of disaster healthcare and a means of improving response performance. PMID- 26262310 TI - Measuring Population Health Using Electronic Health Records: Exploring Biases and Representativeness in a Community Health Information Exchange. AB - Assessment is a core function of public health. Comprehensive clinical data may enhance community health assessment by providing up-to-date, representative data for use in public health programs and policies, especially when combined with community-level data relevant to social determinants. In this study we examine routinely collected and geospatially-enhanced EHR data to assess population health at various levels of geographic granularity available from a regional health information exchange. We present preliminary findings and discuss important biases in EHR data. Future work is needed to develop methods for correcting for those biases to support routine epidemiology work of public health. PMID- 26262311 TI - The Collaborative Coordination of Special Interest Groups on the Telemedicine University Network (RUTE) in Brazil. AB - In Brazil the Telemedicine University Network (Rede Universitaria de Telemedicina RUTE) is an initiative that among others promotes collaboration between university hospitals, universities, and health professionals through information technology infrastructure and special interest groups (SIGs) support. This paper presents results of analyses on collaboration during implementation and coordination activities of RUTE SIGs. This study is based on descriptive statistics and data visualization previously collected by RUTE national coordination relative to the status in July 2014. The analysis through collaboration graph identified the strongest collaboration RUTE units. The graph also highlights the collaborative relationship of RUTE units in form of communities, the most collaborative with each other in a communion in the same SIGs, and the less the collaborative units in the network. It should be stated that the most active units are also the oldest in the community. PMID- 26262312 TI - A Novel Approach to Teach Medical Informatics. AB - The Bern University of Applied Sciences established the first Swiss Bachelor of Science in Medical Informatics. We demonstrate the specifics of the new curriculum that was based on requirements analysis and includes seminars and live case studies to enable problem-solving abilities. PMID- 26262313 TI - Computer Experience of Nurses. AB - This study aimed to identify the computing experience of nurses in southern Brazil, through exploratory survey research. The results, which were obtained from the application of The Staggers Nursing Computer Experience Questionnaire(r), were analyzed by statistical tests. The survey was conducted with nurses working both in hospitals, as in public health, in a capital in southern Brazil. There is the predominance of novice nurses in the application of computer tools in their practices but most often declare the use the computers to develop their professional and also personal life activities. We conclude that the computer and health information systems are part of the working reality of the participants, being considered indispensable resources his activity, while noting limitations on the potential use of these tools. This study reflects on how the issue has been addressed in educational schools and the challenges of inclusion of the theme of Nursing Informatics in the curricula in Brazil. PMID- 26262314 TI - Informatics Competencies in Nursing Management. AB - This study aimed to identify in scientific literature the informatics competencies required from the nurses to make decision in management process. Through a scoping review, literature databases were searched to find articles published in Portuguese, English, or Spanish, until July 2013. 188 articles were found, and seven were included in this study, published between 1994 and 2011. The studies were written in English (5; 71%), in USA (5; 71%), using experience reports or literature review designs (5; 71%). The informatics competences were categorized according the Technology Informatics Guiding Education Reform (TIGER). The findings highlight gaps in informatics competence to make decisions in the management process--essentially in information management competence. PMID- 26262315 TI - Health Informatics Competences for eHealth: What Can We Learn From a Bibliometric Analysis? AB - The appearance of eHealth adds a new dimension to health informatics competencies -they are not necessary just for health providers and health information system users and developers, but also for health consumers. PMID- 26262316 TI - Education, Technology and Health Literacy. AB - The purpose of this study is to develop an interdisciplinary learning environment between education in technology, business, and nursing. This collaboration creates natural interest and motivation for welfare technology. The aim of establishing an interaction between these three areas of expertise is to create an understanding of skills and cultural differences in each area. Futhermore, the aim is to enable future talents to gain knowledge and skills to improve health literacy among senior citizens. Based on a holistic view of welfare technology, a Student Academy was created as a theoretically- and practically-oriented learning center. The mission of the Student Academy is to support and facilitate education in order to maintain and upgrade knowledge and skills in information technology and information management related to e-health and health literacy. The Student Academy inspires students, stakeholders, politicians, DanAge Association members, companies, and professionals to participate in training, projects, workshops, and company visits. PMID- 26262317 TI - Current Status for Teaching Nursing Informatics in Denmark, Canada, and Australia. AB - Nursing schools in Denmark, Canada, and Australia are all currently involved in integrating nursing informatics in the nursing bachelor programme. This paper gives a brief update on the current situation of nursing informatics education for bachelor level nurses in each of the three countries. Whilst there are differences in the curriculum in each county, it is important to share knowledge about undergraduate nursing informatics worldwide to ensure consistency. PMID- 26262318 TI - Trends of Patient Safety Topics Addressed in the Past Five MEDINFO Congresses. AB - Health informatics has been promoted as a core curriculum in our patient safety program for four years. There is a need to let students understand how such topics were addressed with relevant literature of trends in medical informatics. In this study, we performed a content analysis by searching the past five MEDINFO Congress Proceedings. We used MeSH Terms or Keywords to search the study subjects and divided them into three categories. 76 subjects were identified, among which 16 were assigned to Category 1 (System-related), 26 to Category 2 (Database related), and 34 to Category 3 (Others). Some socio-techical issues that emerged in Category 3 presented as future research interests.The identified topics reflect research trends in patient safety. PMID- 26262319 TI - Social Network and Health Researchers and Professionals Mobility in Africa: Lessons Learned from AFRICA BUILD Project. AB - OBJECTIVE: Promote mobility between South-South and South-North for improving level of researchers, staff and students through a platform. METHODS: The methodology is based a filling of a questionnaire about offer or demand. Material is composed a computer connected Internet. RESULT: we registered about 203 demands and 31 offers from partners.43 mobilities were executed completely. CONCLUSION: The results indicate a real need of mobility for researchers and health professionals in Africa. The important number of mobility demands made by external researchers and professionals (from outside the AFRICA BUILD Consortium) may be constrained by the difficulty to find adequate funding. PMID- 26262320 TI - Middleware Supporting Next Generation Data Analytics in Australia. AB - In Australia, as a result of the distributed, often private nature of health provision, tight privacy legislation, even tighter organizational policies, access to data covering the whole patient journey of care is a common aspiration that has been almost impossible to achieve. Access to primary care data in a manner that is record-linkable has been a particular challenge. Since 2006 The University of Melbourne has been developing GRHANITETM Middleware and GRHANITETM Data Linkage technologies designed to overcome these barriers. With over 10% of Australian primary care data now being routinely extracted utilising this technology, we believe the principal technical challenges have now been overcome. We believe this technology to be at the forefront ethically of providing data for research. This poster describes the principal issues involved and the approaches taken in the technical solution underpinning GRHANITETM. PMID- 26262321 TI - Proposal of Local Automatic Weighing Attribute in CBIR. AB - Lung cancer is the most common malignant lesion and the principal cause of cancer related death worldwide. This problem encourages researchers to build computer aided solutions to help diagnose lung cancer. Content-based image retrieval (CBIR) systems are very promising in this context due to a large number of image generated everyday. However, semantic gaps have limited CBIR applicability. This work proposes a new approach to automatically adjust CBIR attribute weights to reflect users' semantic interpretation on retrieval process, minimizing the semantic gap problem and improving retrieval accuracy. PMID- 26262322 TI - Ontology-Driven Semantic Search for Brazilian Portuguese Clinical Notes. AB - The emerging penetration of Health IT in Latin America (especially in Brazil) has exacerbated the ever-increasing amount of Electronic Health Record (EHR) clinical free text documents.This imposes a workflow efficiency challenge on clinicians who need to synthesize such documents during the typically time-constrained patient care. We propose an ontology-driven semantic search framework that effectively supports clinicians' information synthesis at the point of care. PMID- 26262323 TI - Use of Self-Service Query Tools Varies by Experience and Research Knowledge. AB - The lack of understanding of user experience with self-service query tools is a barrier to designing effective query tools and is what propelled this study. User actions were documented and transformed into networks of actions for qualitative analysis. Proficient use of self-service query tools requires significant technical experience. To decrease the user learning curve, additional user education is necessary for novice users. PMID- 26262324 TI - Comparision and analysis of top 10 exercise android Apps in mainland China. AB - Medical guidelines highly recommend physical activity and aerobic exercise in the prevention of primary and secondary cardiovascular disease. The use of exercise promoting application software may improve clinical outcomes for cardiovascular disease (CVD) patients. The study aimed to compare and analyze the functions of the top 10 exercise Android Apps which had more than 1,000,000 downloads from the main four Android App stores in mainland China. The results showed that most of these popular apps had pedometer, exercise plan preset, user data presentation, user encouragement and community sharing functions while a few of them had exercise video clips or animation support and wearable devices. Given these data, the conclusion is that these popular apps fulfill some of the functions recommended by medical guidelines, however, lack of some functions such as pre exercise risk assessment, the exercise intensity recording, specific instructions by professionals, and monitoring functions for CVD patients. PMID- 26262325 TI - 3D Printed Models and Navigation for Skull Base Surgery: Case Report and Virtual Validation. AB - In recent years, computer-assisted surgery tools have become more versatile. Having access to a 3D printed model expands the possibility for surgeons to practice with the particular anatomy of a patient before surgery and improve their skills. Optical navigation is capable of guiding a surgeon according to a previously defined plan. These methods improve accuracy and safety at the moment of executing the operation. We intend to carry on a validation process for computed-assisted tools. The aim of this project is to propose a comparative validation method to enable physicians to evaluate differences between a virtual planned approach trajectory and a real executed course. Summarily, this project is focused on decoding data in order to obtain numerical values so as to establish the quality of surgical procedures. PMID- 26262326 TI - Accuracy of Chest Wall Tumor Resection Guided by Navigation: Experimental Model. AB - Difficulty in identification wall chest tumors lead to unnecessary wide resections. Optical navigation and preoperative virtual planning are assets for surgeries that require exactness and accuracy. These tools enable physicians to study real anatomy before surgery and to follow an established pathway during procedure ensuring effectiveness. The aim of this paper is to demonstrate that Preoperative Virtual Planning is a useful tool in chest tumor interventions to define oncological margins successfully. Moreover, it is possible to use a virtual specimen in order to quantify accuracy. Optical navigation has been used in surgical procedures such as neurosurgery, orthopaedics and ENT over the last ten years. This principle is used in order to orientate the surgeon in three dimensional spaces during the surgery. Surgeons are guided intraoperatively with navigation and are able to obtain a correspondence between images acquired and processed before the surgery and the real anatomy. PMID- 26262327 TI - Identification of Incidental Pulmonary Nodules in Free-text Radiology Reports: An Initial Investigation. AB - Advances in image quality produced by computed tomography (CT) and the growth in the number of image studies currently performed has made the management of incidental pulmonary nodules (IPNs) a challenging task. This research aims to identify IPNs in radiology reports of chest and abdominal CT by Natural Language Processing techiniques to recognize IPN in sentences of radiology reports. Our preliminary analysis indicates vastly different pulmonary incidental findings rates for two different patient groups. PMID- 26262328 TI - Follow-up Recommendation Detection on Radiology Reports with Incidental Pulmonary Nodules. AB - The management of follow-up recommendations is fundamental for the appropriate care of patients with incidental pulmonary findings. The lack of communication of these important findings can result in important actionable information being lost in healthcare provider electronic documents. This study aims to analyze follow-up recommendations in radiology reports containing pulmonary incidental findings by using Natural Language Processing and Regular Expressions. Our evaluation highlights the different follow-up recommendation rates for oncology and non-oncology patient cohorts. The results reveal the need for a context sensitive approach to tracking different patient cohorts in an enterprise-wide assessment. PMID- 26262329 TI - Clinical Trial Feasibility Study Questionnaire Analysis. AB - With the growing complexity and cost of clinical trials (CTs) over the past few decades, Protocol Feasibility (PF) studies have become one of the most critical CT steps in order to avoid costly protocol amendments and ensure the success of CTs. The PF process includes interaction with clinicians located at targeted clinical sites, which results in slow and cumbersome process steps. These process steps are normally supported by information systems that allow users to create, share and collect responses to feasibility questionnaires. This investigation analyzes the systems and questionnaires utilized at several clinical research companies for PF. In addition, it provides recommendations that could eventually improve current methods and systems in place. PMID- 26262330 TI - Extraction Of Adverse Events From Clinical Documents To Support Decision Making Using Semantic Preprocessing. AB - Clinical documentation is usually stored in unstructured format in electronic health records (EHR). Processing the information is inconvenient and time consuming and should be enhanced by computer systems. In this paper, a rule-based method is introduced that identifies adverse events documented in the EHR that occurred during treatment. For this purpose, clinical documents are transformed into a semantic structure from which adverse events are extracted. The method is evaluated in a user study with neurosurgeons. In comparison to a bag of word classification using support vector machines, our approach achieved comparably good results of 65% recall and 78% precision. In conclusion, the rule-based method generates promising results that can support physicians' decision making. Because of the structured format the data can be reused for other purposes as well. PMID- 26262331 TI - Development and evaluation of task-specific NLP framework in China. AB - Natural language processing (NLP) has been designed to convert narrative text into structured data. Although some general NLP architectures have been developed, a task-specific NLP framework to facilitate the effective use of data is still a challenge in lexical resource limited regions, such as China. The purpose of this study is to design and develop a task-specific NLP framework to extract targeted information from particular documents by adopting dedicated algorithms on current limited lexical resources. In this framework, a shared and evolving ontology mechanism was designed. The result has shown that such a free text driven platform will accelerate the NLP technology acceptance in China. PMID- 26262332 TI - Extracting Dependence Relations from Unstructured Medical Text. AB - Dependence relations among disease and risk factors are a key ingredient in risk modeling and decision support models. Currently such information is either provided by experts (costly and time consuming) or extracted from data (if available). The published medical literature represents a promising source of such knowledge; however its manual processing is practically infeasible. While a number of solutions have been introduced to add structure to biomedical literature, none adequately recover dependence relations. The objective of our research is to build such an automatic dependence extraction solution, based on a sequence of natural language processing steps, which take as input a set of MEDLINE abstracts and provide as output a list of structured dependence statements. This paper presents a hybrid pipeline approach, a combination of rule based and machine learning algorithms. We found that this approach outperforms a strictly rule-based approach. PMID- 26262333 TI - A Frequency-based Strategy of Obtaining Sentences from Clinical Data Repository for Crowdsourcing. AB - In clinical NLP, one major barrier to adopting crowdsourcing for NLP annotation is the issue of confidentiality for protected health information (PHI) in clinical narratives. In this paper, we investigated the use of a frequency-based approach to extract sentences without PHI. Our approach is based on the assumption that sentences appearing frequently tend to contain no PHI. Both manual and automatic evaluations on 500 sentences out of the 7.9 million sentences of frequencies higher than one show that no PHI can be found among them. The promising results provide potentials of releasing those sentences for obtaining sentence-level NLP annotations via crowdsourcing. PMID- 26262334 TI - Extraction of Vital Signs from Clinical Notes. AB - Assessment of vital signs is an essential part of surveillance of critically ill patients to detect condition changes and clinical deterioration. While most modern electronic medical records allow for vitals to be recorded in a structured format, the frequency and quality of what is electronically stored may differ from how often these measures are actually recorded. We created a tool that extracts blood pressure, heart rate, temperature, respiratory rate, blood oxygen saturation, and pain level from nursing and other clinical notes recorded in the course of inpatient care to supplement structured vital sign data. PMID- 26262335 TI - Translating ICD-11 into French using lexical-based approach: a preliminary study. AB - To translate the 11th edition of the International Classification of Diseases (ICD-11) into French, we proposed a lexical approach using Natural Language Processing techniques. This method relies on the 56 biomedical terminologies and ontologies included in the Cross-lingual Health Multiple Terminologies and Ontologies Portal. From a sample of 336 ICD-11 terms, the algorithm translated 164 (49%) terms into at least one French term each. PMID- 26262336 TI - Text Mining and Data Modeling of Karyotypes to aid in Drug Repurposing Efforts. AB - Karyotyping, or visually examining and recording chromosomal abnormalities, is commonly used to diagnose and treat disease. Karyotypes are written in the International System for Human Cytogenetic Nomenclature (ISCN), a computationally non-readable language that precludes full analysis of these genomic data. In response, we developed a cytogenetic platform that transfers the ISCN karyotypes to a machine-readable model available for computational analysis. Here we use cytogenetic data from the National Cancer Institute (NCI)-curated Mitelman database1 to create a structured karyotype language. Then, drug-gene-disease triplets are generated via a computational pipeline connecting public drug-gene interaction data sources to identify potential drug repurposing opportunities. PMID- 26262337 TI - Rule-based Cervical Spine Defect Classification Using Medical Narratives. AB - Classifying the defects occurring at the cervical spine provides the basis for surgical treatment planning and therapy recommendation. This process requires evidence from patient records. Further, the degree of a defect needs to be encoded in a standardized from to facilitate data exchange and multimodal interoperability. In this paper, a concept for automatic defect classification based on information extracted from textual data of patient records is presented. In a retrospective study, the classifier is applied to clinical documents and the classification results are evaluated. PMID- 26262338 TI - Comparing Drug-Disease Associations in Clinical Practice Guideline Recommendations and Drug Product Label Indications. AB - Clinical practice guidelines (CPGs) and structured product labels (SPLs) are both intended to promote evidence-based medical practices and guide clinicians' prescribing decisions. However, it is unclear how well CPG recommendations about pharmacologic therapies for certain diseases match SPL indications for recommended drugs. In this study, we use publicly available data and text mining methods to examine drug-disease associations in CPG recommendations and SPL treatment indications for 15 common chronic conditions. Preliminary results suggest that there is a mismatch between guideline-recommended pharmacologic therapies and SPL indications. Conflicting or inconsistent recommendations and indications may complicate clinical decision making and implementation or measurement of best practices. PMID- 26262339 TI - Automated Classification of Pathology Reports. AB - This work develops an automated classifier of pathology reports which infers the topography and the morphology classes of a tumor using codes from the International Classification of Diseases for Oncology (ICD-O). Data from 94,980 patients of the A.C. Camargo Cancer Center was used for training and validation of Naive Bayes classifiers, evaluated by the F1-score. Measures greater than 74% in the topographic group and 61% in the morphologic group are reported. Our work provides a successful baseline for future research for the classification of medical documents written in Portuguese and in other domains. PMID- 26262340 TI - Methods for Sonic Representation of ST Depression During Exercise. AB - Sonic display of ST depression during exercise helps both the patient and the investigator to better identify the transition from normal values to "attention" region and reaching the "alert" threshold. Two types of sonic display were tested, based on combinations of saccadic sounds and different pitch. PMID- 26262341 TI - PIACS: A System for the Automatic Detection, Categorization and Comparison of Scratch-Related Skin Lesions in Dermatology. AB - OBJECTIVE: In the treatment of chronic pruritus-related, scratch-induced skin lesions the categorization, counting and temporal comparison are common methodologies. The observation requires a good memory and expertise in this field to gain comparable findings for this time-consuming process. Digital image processing aims at supporting such manual detections. The objective is to develop a software tool for automatic image detection and comparison. The new photographic setting implies the usage of markers to derive the brightness and size of lesions. MATLAB has been used for the software development. The newly defined setting allows taking standardized images of pruritus-associated cutaneous lesions for detection and comparison. The tool named PIACS (Prurigo Image Analyzing and Comparing System) allows automatically detecting, categorizing and comparing lesions based on digital images. PMID- 26262342 TI - The MFER structure for coding medical signals in real time. AB - We present the structure of the MFER coder to store the medical signals in real time. The MFER is the rules to describe the file with tags the medical signal such as ECG, EEG, etc. However, because the MFER has the simple structure, and is stored as a file unit, it is difficult to process the signal with MFER rules in real-time. To do this, By storing the signal into small unit of time, it is possible to handle as if the signal is stored continuously. The structure of the presented MFER coder is verified in the results. PMID- 26262343 TI - Adding Sound to ECG. AB - This poster presents preliminary results of a project aiming to develop tools for adding sound associated to medical data for potential medical applications. Sonification procedures, the methodology used for testing various sonic representations of ECG, and the results are presented. PMID- 26262344 TI - An Optimized Superpixel Clustering Approach for High-Resolution Chest CT Image Segmentation. AB - Lung segmentation is a fundamental step in many image analysis applications for lung diseases and abnormalities in thoracic computed tomography (CT). However, due to the large variations in pathology that may be present in thoracic CT images, it is difficult to extract the lung regions accurately. A major insight to deal with this problem is the existence of new approaches to cope with quality and performance. This poster presents an optimized superpixel clustering approach for high-resolution chest CT segmentation. The proposed algorithm is compared against some super-pixel algorithms while a performance evaluation is carried out in terms of boundary recall and under-segmentation error metrics. The over segmentation results on a CT Emphysema Database demonstrate that our approach shows better performance than other three state-of-the-art superpixel methods. PMID- 26262345 TI - Automated Image Retrieval of Chest CT Images Based on Local Grey Scale Invariant Features. AB - Textual-based tools are regularly employed to retrieve medical images for reading and interpretation using current retrieval Picture Archiving and Communication Systems (PACS) but pose some drawbacks. All-purpose content-based image retrieval (CBIR) systems are limited when dealing with medical images and do not fit well into PACS workflow and clinical practice. This paper presents an automated image retrieval approach for chest CT images based local grey scale invariant features from a local database. Performance was measured in terms of precision and recall, average retrieval precision (ARP), and average retrieval rate (ARR). Preliminary results have shown the effectiveness of the proposed approach. The prototype is also a useful tool for radiology research and education, providing valuable information to the medical and broader healthcare community. PMID- 26262346 TI - Texture Analysis of Recurrence Plots Based on Wavelets and PSO for Laryngeal Pathologies Detection. AB - This paper deals with the discrimination between healthy and pathological speech signals using recurrence plots and wavelet transform with texture features. Approximation and detail coefficients are obtained from the recurrence plots using Haar wavelet transform, considering one decomposition level. The considered laryngeal pathologies are: paralysis, Reinke's edema and nodules. Accuracy rates above 86% were obtained by means of the employed method. PMID- 26262347 TI - On The Correlation Between Geo-Referenced Clinical Data And Remotely Sensed Air Pollution Maps. AB - This work presents an analysis framework enabling the integration of a clinical administrative dataset of Type 2 Diabetes (T2D) patients with environmental information derived from air quality maps acquired from remote sensing data. The research has been performed within the EU project MOSAIC, which gathers T2D patients' data coming from Fondazione S. Maugeri (FSM) hospital and the Pavia local health care agency (ASL). The proposed analysis is aimed to highlight the complexity of the domain, showing the different perspectives that can be adopted when applying a data-driven approach to large variety of temporal, geo-localized data. We investigated a set of 899 patients, located in the Pavia area, and detected several patterns depicting how clinical facts and air pollution variations may be related. PMID- 26262348 TI - Integrating data from multiple sources for data completeness in a web-based registry for pediatric renal transplantation--the CERTAIN Registry. AB - Patient registries are a useful tool to measure outcomes and compare the effectiveness of therapies in a specific patient population. High data quality and completeness are therefore advantageous for registry analysis. Data integration from multiple sources may increase completeness of the data. The pediatric renal transplantation registry CERTAIN identified Eurotransplant (ET) and the Collaborative Transplant Study (CTS) as possible partners for data exchange. Import and export interfaces with CTS and ET were implemented. All parties reached their projected goals and benefit from the exchange. PMID- 26262349 TI - Development of Unified Lab Test Result Master for Multiple Facilities. AB - A clinical study requires massive amounts of of lab test data, especially for rare diseases. Before creating a protocol, the hypothesis if the protocol will work with enough amount of patients' dataset has to be proved. However, a single facility, such as a university hospital, often faces a lack of number of patients for specific target diseases. Even if collecting datasets from several facilities, there is no active master table that can merge lab test results between the facility datasets. Therefore, the authors develop a unified lab test result master. Because test master standards such as JLAC10 and LOINC are provided from a viewpoint of academic classification of laboratory medicine, the classification does not fit clinical classification, which doctors understand with a mind-set of establishing a clinical study protocol. The authors establish a method to unify masters using an active lab test result master from two university hospitals. PMID- 26262350 TI - Semantic Web Ontology and Data Integration: a Case Study in Aiding Psychiatric Drug Repurposing. AB - There remain significant difficulties selecting probable candidate drugs from existing databases. We describe an ontology-oriented approach to represent the nexus between genes, drugs, phenotypes, symptoms, and diseases from multiple information sources. We also report a case study in which we attempted to explore candidate drugs effective for bipolar disorder and epilepsy. We constructed an ontology incorporating knowledge between the two diseases and performed semantic reasoning tasks with the ontology. The results suggested 48 candidate drugs that hold promise for further breakthrough. The evaluation demonstrated the validity our approach. Our approach prioritizes the candidate drugs that have potential associations among genes, phenotypes and symptoms, and thus facilitates the data integration and drug repurposing in psychiatric disorders. PMID- 26262351 TI - Personalised Medicine Possible With Real-Time Integration of Genomic and Clinical Data To Inform Clinical Decision-Making. AB - Despite widespread use of genomic sequencing in research, there are gaps in our understanding of the performance and provision of genomic sequencing in clinical practice. The Melbourne Genomics Health Alliance (the Alliance), has been established to determine the feasibility, performance and impact of using genomic sequencing as a diagnostic tool. The Alliance has partnered with BioGrid Australia to enable the linkage of genomic sequencing, clinical treatment and outcome data for this project. This integrated dataset of genetic, clinical and patient sourced information will be used by the Alliance to evaluate the potential diagnostic value of genomic sequencing in routine clinical practice. This project will allow the Alliance to provide recommendations to facilitate the integration of genomic sequencing into clinical practice to enable personalised disease treatment. PMID- 26262352 TI - Integration of Disease Specific Clinical and Genomics Datasets using I2B2 Framework. AB - The availability of a patient's genomic profile along with the clinical profile for providing individualized care and treatment is paving the road for a new era of personalized medicine, and is an important area of focus in current biomedical research. One of the prominent and globally implemented solutions for clinical and genomics data integration in biomedical research is an NIH funded NCBC initiative--Informatics for Integrating Biology and the Beside (I2B2). This paper presents the development of a pilot prototype for integrating patient's clinical and genomics datasets using open source and scalable I2B2 Framework. It focuses on disease specific clinical data and genomic variants, when combined together can be used for informed decision making in clinical practices by healthcare professionals and for further investigations by biomedical researchers. The research was carried out using a case study of King Abdullah International Medical Research Center (KAIMRC) in collaboration with King Fahad National Guard Hospital (KFNGH). PMID- 26262353 TI - Bridging the Gap from Bench to Bedside--An Informatics Infrastructure for Integrating Clinical, Genomics and Environmental Data (ICGED). AB - The abundance of heterogeneous biomedical data from a variety of sources demands the development of strategies to address data integration and management issues, so that the data can be used effectively in clinical practices and biomedical research. This research presents an Informatics Infrastructure for Integrating Clinical, Genomics and Environmental Data (ICGED) and provides a roadmap that envisions utilizing the clinical and biomedical resources in our case study. This work describes a data integration approach, proposed by ICGED, with a two-fold purpose: personalized medicine and biomedical data storage and sharing platform. It describes our experiences integrating disease specific clinical and genomics datasets with Data Integration and Analysis Tools (DIAT)--using Informatics for Integrating Biology and the Bedside, and discusses work in progress and future work for extending DIAT, and the development of Risk Assessment and Prediction Tools, Clinical Decision Support Systems and a Bioinformatics Data Warehouse. PMID- 26262354 TI - Designing an Innovative Data Architecture for the Los Angeles Data Resource (LADR). AB - The Los Angeles Data Resource (LADR) is a joint project of major Los Angeles health care provider organizations. The LADR helps clinical investigators to explore the size of potential research study cohorts using operational clinical data across all participating institutions. The Charles R. Drew University of Medicine and Science (CDU) LADR team sought to develop an innovative data architecture that would aggregate de-identified clinical data from safety-net providers in the community into CDU LADR node. This in turn would be federated with the other nodes of LADR for a shared view in a way that was never available before. This led to a self-service system to assess patients matching study criteria at each medical center and to search patients by demographics, ICD-9 codes, lab results and medications. PMID- 26262355 TI - Curating and Integrating Data from Multiple Sources to Support Healthcare Analytics. AB - As the volume and variety of healthcare related data continues to grow, the analysis and use of this data will increasingly depend on the ability to appropriately collect, curate and integrate disparate data from many different sources. We describe our approach to and highlight our experiences with the development of a robust data collection, curation and integration infrastructure that supports healthcare analytics. This system has been successfully applied to the processing of a variety of data types including clinical data from electronic health records and observational studies, genomic data, microbiomic data, self reported data from surveys and self-tracked data from wearable devices from over 600 subjects. The curated data is currently being used to support healthcare analytic applications such as data visualization, patient stratification and predictive modeling. PMID- 26262356 TI - Integrated Database And Knowledge Base For Genomic Prospective Cohort Study In Tohoku Medical Megabank Toward Personalized Prevention And Medicine. AB - The Tohoku Medical Megabank project is a national project to revitalization of the disaster area in the Tohoku region by the Great East Japan Earthquake, and have conducted large-scale prospective genome-cohort study. Along with prospective genome-cohort study, we have developed integrated database and knowledge base which will be key database for realizing personalized prevention and medicine. PMID- 26262357 TI - Non-Integrated Information and Communication Technologies in the Kidney Transplantation Process in Brazil. AB - The entire kidney transplantation process in Brazil is defined through laws, decrees, ordinances, and resolutions, but there is no defined theoretical map describing this process. From this representation it's possible to perform analysis, such as the identification of bottlenecks and information and communication technologies (ICTs) that support this process. The aim of this study was to analyze and represent the kidney transplantation workflow using business process modeling notation (BPMN) and then to identify the ICTs involved in the process. This study was conducted in eight steps, including document analysis and professional evaluation. The results include the BPMN model of the kidney transplantation process in Brazil and the identification of ICTs. We discovered that there are great delays in the process due to there being many different ICTs involved, which can cause information to be poorly integrated. PMID- 26262358 TI - Are we talking about the same patient? AB - The objective of this study is to determine the degree of similarities between the clinical terms used by physicians and nurses in their documentation. PMID- 26262359 TI - An HL7-FHIR-based Object Model for a Home-Centered Data Warehouse for Ambient Assisted Living Environments. AB - Current AAL environments focus on assisting a single person with seperated technologies. There is no interoperability between sub-domains in home environments, like building energy management or housing industry services. BASIS (Building Automation by a Scalable and Intelligent System) aims to integrate all sensors and actuators into a single, efficient home bus. First step is to create a semtically enriched data warehouse object model. We choose FHIR and built an object model mainly based on the Observation, Device and Location resources with minor extensions needed by AAL-foreign sub domains. FHIR turned out to be very flexible and complete for other home related sub-domains. The object model is implemented in a separated software-partition storing all structural and procedural data of BASIS. PMID- 26262360 TI - Data Curation: Improving Environmental Health Data Quality. AB - With the growing recognition of the influence of climate change on human health, scientists' attention to analyzing the relationship between meteorological factors and adverse health effects. However, the paucity of high quality integrated data is one of the great challenges, especially when scientific studies rely on data-intensive computing. This paper aims to design an appropriate curation process to address this problem. We present a data curation workflow that: (i) follows the guidance of DCC Curation Lifecycle Model; (ii) combines manual curation with automatic curation; (iii) and solves environmental health data curation problem. The workflow was applied to a medical knowledge service system and showed that it was capable of improving work efficiency and data quality. PMID- 26262361 TI - Development of a Dynamic and Adaptive Simulator for Health. AB - One of the ways to develop health simulations is through the use of computers. This paper presents the use of Intelligent Computer-aided Instruction (ICAI) for the development of an interactive simulator for learning Cardio Pulmonary Resucitation (CPR) which incorporates online tutorials, training and evaluation. PMID- 26262362 TI - On Analyzing Readmissions Using A Trajectory Model: Evidence From Israel. AB - The problem of readmission, wherein patients are readmitted for the same or a related condition shortly after discharge, has become a challenge worldwide from care quality and financial perspectives. In this study, we explore 30-day readmission data for predicting who is likely to be readmitted and understanding key factors contributing to preventable readmissions using the developmental trajectory of creatinine level as a key laboratory marker of serious illness and a potential predictor of future readmission. Using Electronic Health Record data on 928 patients over ten different visits to emergency departments across Israel, we apply a semi-parametric, statistical, group-based trajectory model to elicit three distinct creatinine-based trajectories over time with differing 30-day readmission rates for males and females. Analysis of readmission risk stratification of the patient population using other relevant factors is ongoing research. PMID- 26262363 TI - Automated Detection of Health Websites' HONcode Conformity: Can N-gram Tokenization Replace Stemming? AB - Authors evaluated supervised automatic classification algorithms for determination of health related web-page compliance with individual HONcode criteria of conduct using varying length character n-gram vectors to represent healthcare web page documents. The training/testing collection comprised web page fragments extracted by HONcode experts during the manual certification process. The authors compared automated classification performance of n-gram tokenization to the automated classification performance of document words and Porter-stemmed document words using a Naive Bayes classifier and DF (document frequency) dimensionality reduction metrics. The study attempted to determine whether the automated, language-independent approach might safely replace word-based classification. Using 5-grams as document features, authors also compared the baseline DF reduction function to Chi-square and Z-score dimensionality reductions. Overall study results indicate that n-gram tokenization provided a potentially viable alternative to document word stemming. PMID- 26262364 TI - Data Science Solution to Event Prediction in Outsourced Clinical Trial Models. AB - Late phase clinical trials are regularly outsourced to a Contract Research Organisation (CRO) while the risk and accountability remain within the sponsor company. Many statistical tasks are delivered by the CRO and later revalidated by the sponsor. Here, we report a technological approach to standardised event prediction. We have built a dynamic web application around an R-package with the aim of delivering reliable event predictions, simplifying communication and increasing trust between the CRO and the in-house statisticians via transparency. Short learning curve, interactivity, reproducibility and data diagnostics are key here. The current implementation is motivated by time-to-event prediction in oncology. We demonstrate a clear benefit of standardisation for both parties. The tool can be used for exploration, communication, sensitivity analysis and generating standard reports. At this point we wish to present this tool and share some of the insights we have gained during the development. PMID- 26262365 TI - Improving Hospital-wide Patient Scheduling Decisions by Clinical Pathway Mining. AB - Recent research has highlighted the need for solving hospital-wide patient scheduling problems. Inpatient scheduling, patient activities have to be scheduled on scarce hospital resources such that temporal relations between activities (e.g. for recovery times) are ensured. Common objectives are, among others, the minimization of the length of stay (LOS). In this paper, we consider a hospital-wide patient scheduling problem with LOS minimization based on uncertain clinical pathways. We approach the problem in three stages: First, we learn most likely clinical pathways using a sequential pattern mining approach. Second, we provide a mathematical model for patient scheduling and finally, we combine the two approaches. In an experimental study carried out using real-world data, we show that our approach outperforms baseline approaches on two metrics. PMID- 26262366 TI - Annotation methods to develop and evaluate an expert system based on natural language processing in electronic medical records. AB - The objective of the SYNODOS collaborative project was to develop a generic IT solution, combining a medical terminology server, a semantic analyser and a knowledge base. The goal of the project was to generate meaningful epidemiological data for various medical domains from the textual content of French medical records. In the context of this project, we built a care pathway oriented conceptual model and corresponding annotation method to develop and evaluate an expert system's knowledge base. The annotation method is based on a semi-automatic process, using a software application (MedIndex). This application exchanges with a cross-lingual multi-termino-ontology portal. The annotator selects the most appropriate medical code proposed for the medical concept in question by the multi-termino-ontology portal and temporally labels the medical concept according to the course of the medical event. This choice of conceptual model and annotation method aims to create a generic database of facts for the secondary use of electronic health records data. PMID- 26262367 TI - "Quartile" screening method to analyze the relationship between HIS and "AEROS" in Japan. AB - Atmospheric pollution affects the health through complex mechanisms and to varying degrees. However, even by secondary usage of retrospective HIS and "AEROS" data, screening can be performed for specific ICD10 diseases caused by environmental factors. Our screening method showed good agreement with doctors' common knowledge on the relationship between atmospheric data and disease. Examples include the higher incidence of influenza at low temperatures and dry skin caused by low humidity, etc. We need to examine the method further in order to make it simpler, easier and more robust. PMID- 26262368 TI - Impact of data quality assessment on development of clinical predictive models. AB - Data quality plays a very important role in predicting clinical outcomes. Data quality is multi dimensional and most relevant studies consider just one or two dimensions. In this study a systematic data quality assessment is performed using four data dimensions. The results demonstrate that performance of predictive models improves when the quality of the data is assessed and addressed systematically. PMID- 26262369 TI - Evaluating Methods for Identifying Cancer in Free-Text Pathology Reports Using Various Machine Learning and Data Preprocessing Approaches. AB - Automated detection methods can address delays and incompleteness in cancer case reporting. Existing automated efforts are largely dependent on complex dictionaries and coded data. Using a gold standard of manually reviewed pathology reports, we evaluated the performance of alternative input formats and decision models on a convenience sample of free-text pathology reports. Results showed that the input format significantly impacted performance, and specific algorithms yielded better results for presicion, recall and accuracy. We conclude that our approach is sufficiently accurate for practical purposes and represents a generalized process. PMID- 26262370 TI - A Metadata based Knowledge Discovery Methodology for Seeding Translational Research. AB - In this paper, we present a semantic, metadata based knowledge discovery methodology for identifying teams of researchers from diverse backgrounds who can collaborate on interdisciplinary research projects: projects in areas that have been identified as high-impact areas at The Ohio State University. This methodology involves the semantic annotation of keywords and the postulation of semantic metrics to improve the efficiency of the path exploration algorithm as well as to rank the results. Results indicate that our methodology can discover groups of experts from diverse areas who can collaborate on translational research projects. PMID- 26262371 TI - Restricted Versus Unrestricted Search Space: Experience from Mining a Large Japanese Database. AB - The aim of this study was to investigate whether standard Big Data mining methods lead to clinically useful results. An association analysis was performed using the apriori algorithm to discover associations among co-morbidities of diabetes patients. Selected data were further analyzed by using k-means clustering with age, long-term blood sugar and cholesterol values. The association analysis led to a multitude of trivial rules. Cluster analysis detected clusters of well and badly managed diabetes patients both belonging to different age groups. The study suggests the usage of cluster analysis on a restricted space to come to meaningful results. PMID- 26262372 TI - Interpreting Medical Information Using Machine Learning and Individual Conditional Expectation. AB - Recently, machine-learning techniques have spread many fields. However, machine learning is still not popular in medical research field due to difficulty of interpreting. In this paper, we introduce a method of interpreting medical information using machine learning technique. The method gave new explanation of partial dependence plot and individual conditional expectation plot from medical research field. PMID- 26262373 TI - A Data Mining Approach to Identify Sexuality Patterns in a Brazilian University Population. AB - This paper presents the profile and experience of sexuality generated from a data mining classification task. We used a database about sexuality and gender violence performed on a university population in southern Brazil. The data mining task identified two relationships between the variables, which enabled the distinction of subgroups that better detail the profile and experience of sexuality. The identification of the relationships between the variables define behavioral models and factors of risk that will help define the algorithms being implemented in the data mining classification task. PMID- 26262374 TI - A Comparative Study of Bayes Net, Naive Bayes and Averaged One-Dependence Estimators for Osteoporosis Analysis. AB - This paper presents an evaluation of the accuracy of the Bayesian classifiers: Bayes Net, Naive Bayes and Averaged One-Dependence Estimator, to support diagnoses of osteopenia and osteoporosis. All classifiers showed good results, thus, given data, it is possible to produce a reasonably accurate estimate of the diagnosis. PMID- 26262375 TI - Trivalent Influenza Vaccine Adverse Event Analysis Based On MedDRA System Organ Classes Using VAERS Data. AB - We studied serious reports following influnza vaccine from VAERS database in year 2011. Our statistical analyses revealed differences of reactions among different age groups and between genders. The results may lead to additional studies to uncover factors contributing to the individual differences in susceptibility to influenza infection. PMID- 26262376 TI - Temporal Relation Extraction in Outcome Variances of Clinical Pathways. AB - Recently the clinical pathway has progressed with digitalization and the analysis of activity. There are many previous studies on the clinical pathway but not many feed directly into medical practice. We constructed a mind map system that applies the spanning tree. This system can visualize temporal relations in outcome variances, and indicate outcomes that affect long-term hospitalization. PMID- 26262377 TI - Proof of Concept HTML5 Webapp: Type 2 Diabetes risk stratification. AB - Proof of concept HTML5 webapp for use in a diabetes screening context is presented. PMID- 26262378 TI - Design of a Graph-Based System for Similar Case Retrieval of Pulmonary Nodules. AB - Due to difficulty of diagnosing lung cancer, it is important to integrate computational tools in the imaging interpretation process. Content-Based Image Retrieval (CBIR) can provide decision support to specialists by allowing them to find nodules from a database that are similar to a reference one. However, CBIR systems still face problems visualizing multidimensional images. This paper presents the design of a graph-based system for the retrieval of similar temporal computed tomography (CT) scans of pulmonary nodules, in order to optimize the visualization of multidimensional images in a CBIR system. Temporal Image Registration has been used to compare reference and retrieved previously segmented nodules. A rooted tree graph is employed to visualize retrieved cases, and it is deployed in a web system for portability and usability purposes. PMID- 26262379 TI - Audit Trail Management System in Community Health Care Information Network. AB - After the Great East Japan Earthquake we constructed a community health care information network system. Focusing on the authentication server and portal server capable of SAML&ID-WSF, we proposed an audit trail management system to look over audit events in a comprehensive manner. Through implementation and experimentation, we verified the effectiveness of our proposed audit trail management system. PMID- 26262380 TI - Utilizing Dental Electronic Health Records Data to Predict Risk for Periodontal Disease. AB - Periodontal disease is a major cause for tooth loss and adversely affects individuals' oral health and quality of life. Research shows its potential association with systemic diseases like diabetes and cardiovascular disease, and social habits such as smoking. This study explores mining potential risk factors from dental electronic health records to predict and display patients' contextualized risk for periodontal disease. We retrieved relevant risk factors from structured and unstructured data on 2,370 patients who underwent comprehensive oral examinations at the Indiana University School of Dentistry, Indianapolis, IN, USA. Predicting overall risk and displaying relationships between risk factors and their influence on the patient's oral and general health can be a powerful educational and disease management tool for patients and clinicians at the point of care. PMID- 26262381 TI - Distributed Parallel Computing in Data Analysis of Osteoporosis. AB - This research aimed to compare the performance of two models of load balancing (Proportional and Autotuned algorithms) of the JPPF platform in the processing of data mining from a database with osteoporosis and osteopenia. When performing the analysis of execution times, it was observed that the Proportional algorithm performed better in all cases. PMID- 26262382 TI - Kmer-indexer: A Fast K-mer Indexing Program. AB - In our previous work, a k-mer based program named MFEprimer-2.0 was designed and developed for primer specificity evaluation task. In order to increase the index processing speed, decrease the index data size and memory usage, we developed a new program named kmer-indexer. Compared to MFEprimer-2.0, the processing speed of kmer-indexer is 10+ times faster, the index data size can be significantly reduced to one third, and the memory usage is controlled within a small range so that this program can run on an ordinary PC. PMID- 26262383 TI - Cohort Discovery Query Optimization via Computable Controlled Vocabulary Versioning. AB - Self-service cohort discovery tools strive to provide intuitive interfaces to large Clinical Data Warehouses that contain extensive historic information. In those tools, controlled vocabulary (e.g., ICD-9-CM, CPT) coded clinical information is often the main search criteria used because of its ubiquity in billing processes. These tools generally require a researcher to pick specific terms from the controlled vocabulary. However, controlled vocabularies evolve over time as medical knowledge changes and can even be replaced with new versions (e.g., ICD-9 to ICD-10). These tools generally only display the current version of the controlled vocabulary. Researchers should not be expected to understand the underlying controlled vocabulary versioning issues. We propose a computable controlled vocabulary versioning system that allows cohort discovery tools to automatically expand queries to account for terminology changes. PMID- 26262384 TI - A Statistical Analysis of Term Occurrences in Radiology Reporting. AB - To compare term occurrences in free-text radiology reports and RSNA reporting templates, we selected five templates from an RSNA reporting template library and their corresponding free-text reports as a test set, and employed the Wilcoxon signed-rank test to find out whether the terms in RSNA reporting templates match those terms appearing in corresponding free-text radiology reports. The results show that most terms in free-text radiology reports are covered by RSNA reporting templates. By assessing the terminology coverage of existing templates, this study may benefit the growth of the RSNA reporting template library. PMID- 26262385 TI - Is it Possible to Make Everyone Talk in the Same Language? AB - Speaking the same language is a vital pre-requisite in verbal communication. The same applies in sharing health information among medical professionals in rendering care to patients. The Hospital Authority of Hong Kong developed its own clinical vocabulary table (HACVT) for clinicians to document diagnoses and procedures directly in the Clinical Management System (CMS) since 1996. HACVT is referenced to international classifications and reference terminologies, with local terms added and is built according to the principles of terminology management [1]. This poster describes the process of data standardisation within the organisation in the past years to achieve data interoperability through different adoption methods of HACVT. PMID- 26262386 TI - A Novel Approach to Create a Machine Readable Concept Model for Validating SNOMED CT Concept Post-coordination. AB - Post-coordination provides the means to achieve an appropriate content coverage, which is critical in successfully adopting clinical reference terminologies, and thus represent clinical information consistently. However, one of the major problems of post-coordination corresponds with ensuring only clinically sensible concepts can be constructed. In this poster, we present the development of a novel approach to generate a MRCM computationally, in order to facilitate the adherence to the existing guidelines and improve the quality of post-coordination in SNOMED CT. PMID- 26262387 TI - Towards a Clinical Decision Support System for Drug Allergy Management: Are Existing Drug Reference Terminologies Sufficient for Identifying Substitutes and Cross-Reactants? AB - Drug allergy cross-reactivity checking is an important component of electronic health record systems. Currently, a single, open-source medication dictionary that can provide this function does not exist. In this study, we assessed the feasibility of using RxNorm and NDF-RT (National Drug File--Reference Terminology) for allergy management decision support. We evaluated the performance of using the Pharmacological Class, Mechanism of Action and Chemical Structure NDF-RT classifications in discriminating between safe and cross reactive alternatives to a sample of common drug allergens. The positive predictive values for the three approaches were 96.3%, 99.3% and 96.2% respectively. The negative predictive values were 94.7%, 56.8% and 92.6%. Our findings suggest that in the absence of an established medication allergy classification system, using the Pharmacologic Class and Chemical Structure classifications in NDF-RT may still be effective for discriminating between safe and cross-reactive alternatives to potential allergens. PMID- 26262388 TI - Consumer Health Vocabulary: A Proposal for a Brazilian Portuguese Language. AB - Studies show a gap between the expressions commonly used by health consumers and health professionals. To bridge this gap, consumer health vocabularies are presented as a solution. The aim of this paper is to describe an on-going project to create a consumer health vocabulary (CHV) in the Brazilian Portuguese language. This project will be developed in three phases: terms extraction and connection to compose a CHV graph structure, human validation, and computacional application development. We expect to make a CHV beta version (including approximately 5,000 valid consumer terms stored in a database graph) available. This project can contribute to the improvement of CHVs. PMID- 26262390 TI - National governance of archetypes in Norway. AB - Norwegian National ICT has implemented a national governance scheme for archetypes. The scheme uses openEHR, and is possibly the first of its kind worldwide. It introduces several new processes and methods for crowd sourcing clinician input. It has spent much of its first year establishing practical processes and recruiting clinicians, and only a few archetypes has been reviewed and approved. Some non-reusable archetypes have emerged while the governance scheme has established itself, which demonstrates the need for a centralised governance. As the mass of clinician involvement reached a critical point at the end of 2014, the rate of archetype review and approval increased. PMID- 26262389 TI - ICHI Categorial Structure: a WHO-FIC Tool for Semantic Interoperability of Procedures Classifications. AB - Casemix grouping using procedures classifications has become an important use case for health care terminologies. There are so many different national procedures classifications used for Casemix grouping that it is not possible to agree on a worldwide standard. ICHI (International Classification of Health Interventions) is proposing an approach that standardises only the terminologies' model structure. The poster shows the use of the ICHI alpha to replace ICD9 CM Volume 3 in the UNU-CBG International Casemix grouper. PMID- 26262391 TI - Textual Definitions in the Leukemia Domain: Methodological Guidelines for Biomedical Ontologies. AB - The goal of our study is to establish methodological guidelines for the formulation of definitions in biomedical ontologies thatare not so common in the field of Library & Information Science. PMID- 26262392 TI - A Pilot Study on Modeling of Diagnostic Criteria Using OWL and SWRL. AB - The objective of this study is to describe our efforts in a pilot study on modeling diagnostic criteria using a Semantic Web-based approach. We reused the basic framework of the ICD-11 content model and refined it into an operational model in the Web Ontology Language (OWL). The refinement is based on a bottom-up analysis method, in which we analyzed data elements (including value sets) in a collection (n=20) of randomly selected diagnostic criteria. We also performed a case study to formalize rule logic in the diagnostic criteria of metabolic syndrome using the Semantic Web Rule Language (SWRL). The results demonstrated that it is feasible to use OWL and SWRL to formalize the diagnostic criteria knowledge, and to execute the rules through reasoning. PMID- 26262393 TI - Constructing a Graph Database for Semantic Literature-Based Discovery. AB - Literature-based discovery (LBD) generates discoveries, or hypotheses, by combining what is already known in the literature. Potential discoveries have the form of relations between biomedical concepts; for example, a drug may be determined to treat a disease other than the one for which it was intended. LBD views the knowledge in a domain as a network; a set of concepts along with the relations between them. As a starting point, we used SemMedDB, a database of semantic relations between biomedical concepts extracted with SemRep from Medline. SemMedDB is distributed as a MySQL relational database, which has some problems when dealing with network data. We transformed and uploaded SemMedDB into the Neo4j graph database, and implemented the basic LBD discovery algorithms with the Cypher query language. We conclude that storing the data needed for semantic LBD is more natural in a graph database. Also, implementing LBD discovery algorithms is conceptually simpler with a graph query language when compared with standard SQL. PMID- 26262394 TI - Development of an Ontology to Recommend Exercises from Conceptual Maps. AB - The recommendation of exercise plans requires several variables to be considered (e.g., patient's conditions and preferences) and are normally complex to analyze. To facilitate this analysis we proposed the creation of an ontology to assist professionals to recommend exercises. We interviewed 2 experts and this resulted in IDEF diagram and conceptual map. The conceptual map proved to be the preferred way that experts gained more understanding compared with the IDEF diagram. In addition, we also used the conceptual map to validate the formal structure of experts' ideas. From the conceptual map we created an ontology that is being reviewed. After this, we plan to incorporate the ontology into a decision support system that will assist professionals to recommend exercises for their patients. PMID- 26262395 TI - Utility of Arden Syntax for Representation of Fuzzy Logic in Clinical Quality Measures. AB - BACKGROUND: Prior work has established that fuzzy logic is prevalent in clinical practice guidelines and that Arden Syntax is suitable for representing clinical quality measures (CQMs). Approved since then, Arden Syntax v2.9 (2012) has formal constructs for fuzzy logic even as new formalisms are proposed to represent quality logic. OBJECTIVES: Determine the prevalence of fuzzy logic in CQMs and assess the utility of a contemporary version of Arden Syntax for representing them. METHODS: Linguistic variables were tabulated in the 329 Assessing Care of the Vulnerable Elderly (ACOVE-3) CQMs, and these logic statements were encoded in Arden Syntax. RESULTS: In a total of 392 CQMs, linguistic variables occurred in 30.6%, and Arden Syntax could be used to represent these formally. CONCLUSIONS: Fuzzy logic occurs commonly in CQMs, and Arden Syntax offers particular utility for the representations of these constructs. PMID- 26262396 TI - Developing a Standards-Based Information Model for Representing Computable Diagnostic Criteria: A Feasibility Study of the NQF Quality Data Model. AB - The lack of a standards-based information model has been recognized as a major barrier for representing computable diagnostic criteria. In this paper we describe our efforts in examining the feasibility of the Quality Data Model (QDM) developed by the National Quality Forum (NQF)-for representing computable diagnostic criteria. We collected the diagnostic criteria for a number of diseases and disorders (n=12) from textbooks and profiled the data elements of the criteria using the QDM data elements. We identified a number of common patterns informed by the QDM. In conclusion, the common patterns informed by the QDM are useful and feasible in building a standards-based information model for computable diagnostic criteria. PMID- 26262398 TI - Development of an Adolescent Depression Ontology for Analyzing Social Data. AB - Depression in adolescence is associated with significant suicidality. Therefore, it is important to detect the risk for depression and provide timely care to adolescents. This study aims to develop an ontology for collecting and analyzing social media data about adolescent depression. This ontology was developed using the 'ontology development 101'. The important terms were extracted from several clinical practice guidelines and postings on Social Network Service. We extracted 777 terms, which were categorized into 'risk factors', 'sign and symptoms', 'screening', 'diagnosis', 'treatment', and 'prevention'. An ontology developed in this study can be used as a framework to understand adolescent depression using unstructured data from social media. PMID- 26262397 TI - A Standards-based Semantic Metadata Repository to Support EHR-driven Phenotype Authoring and Execution. AB - This study describes our efforts in developing a standards-based semantic metadata repository for supporting electronic health record (EHR)-driven phenotype authoring and execution. Our system comprises three layers: 1) a semantic data element repository layer; 2) a semantic services layer; and 3) a phenotype application layer. In a prototype implementation, we developed the repository and services through integrating the data elements from both Quality Data Model (QDM) and HL7 Fast Healthcare Inteoroperability Resources (FHIR) models. We discuss the modeling challenges and the potential of our system to support EHR phenotype authoring and execution applications. PMID- 26262399 TI - A Framework for Modeling Workflow Execution by an Interdisciplinary Healthcare Team. AB - The use of business workflow models in healthcare is limited because of insufficient capture of complexities associated with behavior of interdisciplinary healthcare teams that execute healthcare workflows. In this paper we present a novel framework that builds on the well-founded business workflow model formalism and related infrastructures and introduces a formal semantic layer that describes selected aspects of team dynamics and supports their real-time operationalization. PMID- 26262400 TI - Evaluating a Hierarchical Clinical Event Linkage Model for Clinic-Specific Databases. AB - A relational database model is presented that stores the hierarchical linkages between clinical events with qualifier codes, such that the explicit contextual meaning of an event's attributes is preserved upon retrieval. A retrospective analysis of 302 forms built upon the model showed that 91% of 17,899 data elements requested by clinicians and researchers from 19 clinics were successfully represented, but that 62% were never used more than once. These results reinforce the specificity of clinic-specific databases and the need for unambiguous, explicitly-stored clinical data. PMID- 26262401 TI - Enabling Self-Monitoring Data Exchange in Participatory Medicine. AB - The development of new methods, devices and apps for self-monitoring have enabled the extension of the application of these approaches for consumer health and research purposes. The increase in the number and variety of devices has generated a complex scenario where reporting guidelines and data exchange formats will be needed to ensure the quality of the information and the reproducibility of results of the experiments. Based on the Minimal Information for Self Monitoring Experiments (MISME) reporting guideline we have developed an XML format (MISME-ML) to facilitate data exchange for self monitoring experiments. We have also developed a sample instance to illustrate the concept and a Java MISME ML validation tool. The implementation and adoption of these tools should contribute to the consolidation of a set of methods that ensure the reproducibility of self monitoring experiments for research purposes. PMID- 26262402 TI - DServO: A Peer-to-Peer-based Approach to Biomedical Ontology Repositories. AB - We present in this poster an extension of the ServO ontology server system, which adopts a decentralized Peer-To-Peer approach for managing multiple heterogeneous knowledge organization systems. It relies on the use of the JXTA protocol coupled with information retrieval techniques to provide a decentralized infrastructure for managing multiples instances of Ontology Repositories. PMID- 26262403 TI - OntoMama: An Ontology Applied to Breast Cancer. AB - This article describes the process of building an ontology to assist medical students and professionals specialized in Oncology. The ontology allows the user to obtain knowledge more quickly and thus assist professionals in their decision making. PMID- 26262404 TI - National Healthcare Policies in Chile: An Ontological Meta-Analysis. AB - We present an ontological meta-analysis of the national healthcare policies in Chile. Using a logically constructed ontology based on the common body of knowledge as a lens, we map the 39 key policies. The ontological map provides a synoptic, systematic, and systemic view of the policies, and highlight their emphases and biases. PMID- 26262405 TI - Modelling the Medication Management System for Resource Limited Settings: A Formal Representation of the Prescribing and Dispensing Phases. AB - We propose a conceptual data model for relational databases targeting the prescribing and dispensing phases of the medication management system. The model was developed using recommendations from existing standards and guidelines, with necessary modifications made to suit adoption in resource-limited settings. We present the model as an entity-relationship diagram with 10 entities, 12 relationships and 48 attributes. It is our hope that this work will help mitigate barriers in the implementation of electronic prescribing and dispensing standards in the developing world. PMID- 26262406 TI - Real-time Data Fusion Platforms: The Need of Multi-dimensional Data-driven Research in Biomedical Informatics. AB - Systems designed to expedite data preprocessing tasks such as data discovery, interpretation, and integration that are required before data analysis drastically impact the pace of biomedical informatics research. Current commercial interactive and real-time data integration tools are designed for large-scale business analytics requirements. In this paper we identify the need for end-to-end data fusion platforms from the researcher's perspective, supporting ad-hoc data interpretation and integration. PMID- 26262407 TI - Towards a Formal Representation of Processes and Objects Regarding the Delivery of Telehealth Services: The Telehealth Ontology (TEON). AB - This study introduces ontological aspects concerning the Telehealth Ontology (TEON), an ontology that represents formal-ontological content concerning the delivery of telehealth services. TEON formally represents the main services, actors and other entity types relevant to telehealth service delivery. TEON uses the upper level ontology BioTopLite2 and reuses content from the Ontology for Biomedical Investigations (OBI). The services embedded in telehealth services are considered as essential as the common services provided by the health-related practices. We envision TEON as a service to support the development of telehealth systems. TEON might also enable the integration of heterogeneous telehealth systems, and provide a base to automatize the processing of telehealth-related content. PMID- 26262408 TI - Characterizing Health Information for Different Target Audiences. AB - Different groups of audiences in health care: health professionals and health consumers, each have different information needs. Health monographs targeting different audiences are created by leveraging readers' background knowledge. The NCI's Physician Data Query (PDQ(r)) Cancer Information Summaries provide parallel cancer information and education resources with different target audiences. In this paper, we used targeted audience-specific cancer information PDQs to measure characteristic differences on the element level between audiences. In addition, we compared vocabulary coverage. Results show a significant difference between the professional and patient version of cancer monographs in both content organization and vocabulary. This study provides a new view to assess targeted audience-specific health information, and helps editors to improve the quality and readability of health information. PMID- 26262409 TI - A Pilot Ontology for Healthcare Quality Indicators. AB - Computerisation of quality indicators for the English National Health Service currently relies primarily on queries and clinical coding, with little use of ontologies. We created a searchable ontology for a diverse set of healthcare quality indicators. We investigated attributes and relationships in a set of 222 quality indicators, categorised by clinical pathway, inclusion and exclusion criteria and US Institute of Medicine purpose. Our pilot ontology could reduce duplication of effort in healthcare quality monitoring. PMID- 26262410 TI - Fuzzy-Arden-Syntax-based, Vendor-agnostic, Scalable Clinical Decision Support and Monitoring Platform. AB - This study's objective is to develop and use a scalable genuine technology platform for clinical decision support based on Arden Syntax, which was extended by fuzzy set theory and fuzzy logic. Arden Syntax is a widely recognized formal language for representing clinical and scientific knowledge in an executable format, and is maintained by Health Level Seven (HL7) International and approved by the American National Standards Institute (ANSI). Fuzzy set theory and logic permit the representation of knowledge and automated reasoning under linguistic and propositional uncertainty. These forms of uncertainty are a common feature of patients' medical data, the body of medical knowledge, and deductive clinical reasoning. PMID- 26262411 TI - Online Training Assessment For Primary Care Professionals Of The City Of Sao Paulo. AB - Students who participate in courses and training offered in distance mode receive positive results in learning evaluations. Most studies show improvement in knowledge in pre- and post- course comparisons; however, there are still few evaluations of long-term knowledge retention. This study compares the learning scores of online training for health professionals in three different times: before training, immediately after, and 180 days later. This technological production research includes quantitative, descriptive and multivariate correlational, longitudinal, and panel types. The results show that online training has a positive impact on learning and knowledge retention. Whereas learning can be related to the impact of training, i.e., with the transfer of what was gathered for professional practice, learning retention of online training applied to health professionals represents an important step and assists in identifying the best strategies so expected results are achieved. PMID- 26262412 TI - Allergy Risk Finder: Hypothesis Generation System for Allergy Risks via Web Service. AB - This study's aim was to build a web service that automatically collects and tests hypotheses for possible allergy risks. We crowdsourced for unknown allergy risks, and obtained odds ratios. By using the collected hypotheses, we built a web service that estimates allergy risks from a questionnaire (consisting of 10 questions that we gathered from the crowdsourcing task), and at the end, we asked the users their new hypotheses on possible allergy risks. The web service also asked the users to send their original hypotheses to contribute to find the cause of allergy. In the near future, clinical trials to validate the hypotheses found in this study are desired. PMID- 26262413 TI - Toward a Global eHealth Observatory for Nursing. AB - This poster summarizes a review of existing health observatories and proposes a new entity for nursing. A nursing eHealth observatory would be an authoritative and respected source of eHealth information that would support nursing decision making and policy development and add to the body of knowledge about professional nursing and client care outcomes. PMID- 26262414 TI - Representation of Biomedical Expertise in Ontologies: a Case Study about Knowledge Acquisition on HTLV viruses and their clinical manifestations. AB - In this paper, we introduce a set of methodological steps for knowledge acquisition applied to the organization of biomedical information through ontologies. Those steps are tested in a real case involving Human T Cell Lymphotropic Virus (HTLV), which causes myriad infectious diseases. We hope to contribute to providing suitable knowledge representation of scientific domains. PMID- 26262415 TI - Trigger Development for the Improvement of Neurological Patient Care. AB - By analyzing medical records, we developed triggers for epilepsy patients' care coordination. Thirteen triggers with potential to affect patient care outcomes and safety were found. PMID- 26262416 TI - Patient Empowerment through Personal Medical Recommendations. AB - Patients today have ample opportunities to inform themselves about their disease and possible treatments using the Internet. While this type of patient empowerment is widely regarded as having a positive influence on the treatment, there exists the problem that the quality of information that can be found on online is very diverse. This paper presents a platform which empowers patients by allowing searching in a high quality document repository. In addition, it automatically provides intelligent and personalized recommendations according to the individual preferences and medical conditions. PMID- 26262417 TI - A software tool to analyze clinical workflows from direct observations. AB - Observational data of clinical processes need to be managed in a convenient way, so that process information is reliable, valid and viable for further analysis. However, existing tools for allocating observations fail in systematic data collection of specific workflow recordings. We present a software tool which was developed to facilitate the analysis of clinical process observations. The tool was successfully used in the project OntoHealth, to build, store and analyze observations of diabetes routine consultations. PMID- 26262418 TI - Knowledge-based immunosuppressive therapy for kidney transplant patients--from theoretical model to clinical integration. AB - Immunosuppressive therapy is a risky necessity after a patient received a kidney transplant. To reduce risks, a knowledge-based system was developed that determines the right dosage of the immunosuppresive agent Tacrolimus. A theoretical model, to classify medication blood levels as well as medication adaptions, was created using data from almost 500 patients, and over 13.000 examinations. This model was then translated into an Arden Syntax knowledge base, and integrated directly into the hospital information system of the Vienna General Hospital. In this paper we give an overview of the construction and integration of such a system. PMID- 26262419 TI - Clinical application of the integrated multicenter discharge summary database. AB - We performed the multi-year project to collect discharge summary from multiple hospitals and made the big text database to build a common document vector space, and developed various applications. We extracted 243,907 discharge summaries from seven hospitals. There was a difference in term structure and number of terms between the hospitals, however the differences by disease were similar. We built the vector space using TF-IDF method. We performed a cross-match analysis of DPC selection among seven hospitals. About 80% cases were correctly matched. The use of model data of other hospitals reduced selection rate to around 10%; however, integrated model data from all hospitals restored the selection rate. PMID- 26262420 TI - Oncotherapy: A System for Requesting Chemotherapy Protocols. AB - A clinical decision support system is able to provide oncologists with suitable treatment options at the moment of decision making regarding which chemotherapy protocol is the best to apply to a particular oncological case. The National Cancer Institute has created a Guidelines Committee that establishes therapeutical options for each clinical case. The Health Informatics Department has developed Oncotherapy, a knowledge database that incorporates information provided by the Guidelines Committee. Oncotherapy includes a tailored information repository to provide oncologists in the public health system with the chemotherapy protocols available given three types of data: clinical diagnosis, clinical stage and therapy criteria. The protocol selected by the treating oncologist is sent back to Oncotherapy, which may create new knowledge that can be incorporated into the knowledge database. In this way, the system supports making the best decision according to the chemotherapy protocol options available. Furthermore, it can warn of errors that could result from mistakenly chosen therapies. PMID- 26262421 TI - Linked Health Data: how linked data can help provide better health decisions. AB - This paper provides a brief survey about the use of linked data in healthcare to foster better health decisions and increase health knowledge. We present real cases from the Brazilian experience and emphasize some issues in research. This paper is not intending to be fully comprehensive, we discuss some open issues and research challenges in linked data and the technologies involved. We conclude that even though linked data has been adopted in many countries, some challenges have to be overcome, for example, interoperability between different standards. A defined solution able to foster the semantic interoperability between different standards must be developed. Benefits contributed through linked health data involve better decision making on diagnostics, assertive treatments, knowledge acquisition, improvements in quality healthcare service to citizens. PMID- 26262422 TI - Facilitating Full-text Access to Biomedical Literature Using Open Access Resources. AB - Open access (OA) resources and local libraries often have their own literature databases, especially in the field of biomedicine. We have developed a method of linking a local library to a biomedical OA resource facilitating researchers' full-text article access. The method uses a model based on vector space to measure similarities between two articles in local library and OA resources. The method achieved an F-score of 99.61%. This method of article linkage and mapping between local library and OA resources is available for use. Through this work, we have improved the full-text access of the biomedical OA resources. PMID- 26262423 TI - What Medical Informaticians Do With and Think About an International Medical Informatics Listserv: Member Survey Preliminary Findings. AB - A survey of members of the American Medical Informatics Association (AMIA) listserv Forum on implementation and optimization asked how members perceived the Forum, and suggestions for improvement. Respondents appear to be remarkably engaged with the Forum's debates, information sharing, educational and practical teachings, comments, and immediacy. PMID- 26262424 TI - A Comparison between LMS tools to support e-health educational activities. AB - The objective of this study is to understand how a Learning Management System (LMS) plataform is used in a telehealth center to support two virtual learning enviroments focused on the education of the healthcare professionals and the students of a medical schoool. The study outcome is expected to provide indications towards choosing a better LSM for the telehelath center to support their educacional activities. PMID- 26262429 TI - Phagraphene: A Low-Energy Graphene Allotrope Composed of 5-6-7 Carbon Rings with Distorted Dirac Cones. AB - Using systematic evolutionary structure searching we propose a new carbon allotrope, phagraphene [fae'graefi:n], standing for penta-hexa-hepta-graphene, because the structure is composed of 5-6-7 carbon rings. This two-dimensional (2D) carbon structure is lower in energy than most of the predicted 2D carbon allotropes due to its sp(2)-binding features and density of atomic packing comparable to graphene. More interestingly, the electronic structure of phagraphene has distorted Dirac cones. The direction-dependent cones are further proved to be robust against external strain with tunable Fermi velocities. PMID- 26262428 TI - Control of Auditory Attention in Children With Specific Language Impairment. AB - PURPOSE: Children with specific language impairment (SLI) appear to demonstrate deficits in attention and its control. Selective attention involves the cognitive control of attention directed toward a relevant stimulus and simultaneous inhibition of attention toward irrelevant stimuli. The current study examined attention control during a cross-modal word recognition task. METHOD: Twenty participants with SLI (ages 9-12 years) and 20 age-matched peers with typical language development (TLD) listened to words through headphones and were instructed to attend to the words in 1 ear while ignoring the words in the other ear. They were simultaneously presented with pictures and asked to make a lexical decision about whether the pictures and auditory words were the same or different. Accuracy and reaction time were measured in 5 conditions, in which the stimulus in the unattended channel was manipulated. RESULTS: The groups performed with similar accuracy. Compared with their peers with TLD, children with SLI had slower reaction times overall and different within-group patterns of performance by condition. CONCLUSIONS: Children with TLD showed efficient inhibitory control in conditions that required active suppression of competing stimuli. Participants with SLI had difficulty exerting control over their auditory attention in all conditions, with particular difficulty inhibiting distractors of all types. PMID- 26262430 TI - Ulleungamides A and B, Modified alpha,beta-Dehydropipecolic Acid Containing Cyclic Depsipeptides from Streptomyces sp. KCB13F003. AB - Two novel cyclic depsipeptides, ulleungamides A (1) and B (2), were isolated from cultures of terrestrial Streptomyces sp. Their structures were determined by analyses of spectroscopic data and various chemical transformations, including modified Mosher's method, advanced Marfey's method, PGME, GITC derivatizations, and Snatzke's method. Ulleungamides were determined to be a new class of peptides bearing unprecedented units, such as 5-hydroxy-6-methyl-2,3-dehydropipecolic acid, 4,5-dihydroxy-6-methyl-2,3-dehydropipecolic acid, and amino-linked 2 isopropylsuccinic acid. Ulleungamide A displayed growth inhibitory activity against Staphylococcus aureus and Salmonella typhimurium without cytotoxicity. PMID- 26262431 TI - Superconductivity with Topological Surface State in SrxBi2Se3. AB - By intercalation of alkaline earth metal Sr in Bi2Se3, superconductivity with large shielding volume fraction (~91.5% at 0.5 K) has been achieved in Sr0.065Bi2Se3. Analysis of the Shubnikov-de Hass oscillations confirms the half shift expected from a Dirac spectrum, giving transport evidence of the existence of surface states. Importantly, SrxBi2Se3 superconductor is stable under air, making SrxBi2Se3 an ideal material base for investigating topological superconductivity. PMID- 26262432 TI - Reversible Piezofluorochromic Property and Intrinsic Structure Changes of Tetra(4 methoxyphenyl)ethylene under High Pressure. AB - During the past decade, luminescent mechanochromism has received much attention. Despite the garnered attention, only a few studies have reported the effect of internal molecular structure change on the performance of mechanochromic fluorescence. Here, we chose tetra(4-methoxyphenyl)ethylene (TMOE) as a model molecule to study the correlation between structure and fluorescence property under a hydrostatic pressure produced by a diamond anvil cell (DAC). TMOE is a methoxy-substituted tetraphenylethylene (TPE) derivative and has a nearly centrosymmetric structure and a natural propeller shape. Ultraviolet-visible absorption and fluorescence spectra of TMOE and TPE in solution proved that the presence of methoxy groups in TMOE is responsible for the difference in fluorescence emissions of TMOE and TPE. Under a hydrostatic pressure, the in situ fluorescence spectra of TMOE at different concentrations show that the fluorescence intensity gradually weakens, accompanied by an obvious redshift. The Raman peak intensities decrease gradually, and the peaks disappear eventually with the pressure increasing. These spectral changes are attributed to the changes in the intramolecular conformation, that is, the strengthening of the weak C-H...O hydrogen bonds in TMOE molecules, which is caused by the twisted dihedral angle between the benzene ring and the carbon rigid plane of ethylene. Density functional theory simulation further confirms that the decreased dihedral angle could weaken Raman peak intensity, which is consistent with our experimental results. PMID- 26262433 TI - Observing Changes in the Structure and Oligomerization State of a Helical Protein Dimer Using Solid-State Nanopores. AB - Protein analysis using solid-state nanopores is challenging due to limitations in bandwidth and signal-to-noise ratio. Recent improvements of those two aspects have made feasible the study of small peptides using solid-state nanopores, which have an advantage over biological counterparts in tunability of the pore diameter. Here, we report on the detection and characterization of peptides as small as 33 amino acids. Silicon nitride nanopores with thicknesses less than 10 nm are used to provide signal-to-noise (S/N) levels up to S/N ~ 10 at 100 kHz. We demonstrate differentiation of monomer and dimer forms of the GCN4-p1 leucine zipper, a coiled-coil structure well studied in molecular biology, and compare with the unstructured 33-residue monomer. GCN4-p1 is sequence segment associated with homodimerization of the transcription factor General Control Nonderepressible 4 (GCN4), which is involved in the control of amino acid synthesis in yeast. The differentiation between two oligomeric forms demonstrates the capabilities of improved solid-state nanopore platforms to extract structural information involving short peptide structures. PMID- 26262435 TI - Cancer Incidence and Mortality in Patients Treated Either With RAI or Thyroidectomy for Hyperthyroidism. AB - CONTEXT: Some previous studies have suggested increased cancer risk in hyperthyroid patients treated with radioactive iodine (RAI). It is unclear whether the excess cancer risk is attributable to hyperthyroidism, its treatment, or the shared risk factors of the two diseases. OBJECTIVE: The objective was to assess cancer morbidity and mortality in hyperthyroid patients treated with either RAI or surgery. PATIENTS: We identified 4334 patients treated surgically for hyperthyroidism in Finland during 1986-2007 from the Hospital Discharge Registry and 1814 patients treated with RAI for hyperthyroidism at Tampere University Hospital. For each patient, three age- and gender-matched controls were chosen. Information on cancer diagnoses was obtained from the Cancer Registry. The follow-up began 3 months after the treatment and ended at cancer diagnosis, death, emigration, or the common closing date (December 31, 2009). RESULTS: The overall cancer incidence was not increased among the hyperthyroid patients compared to their controls (rate ratio [RR], 1.05; 95% confidence interval [CI], 0.96-1.15). However, the risk of cancers of the respiratory tract (RR, 1.46; 95% CI, 1.05-2.02) and the stomach (RR, 1.64; 95% CI, 1.01-2.68) was increased among the patients. The overall cancer mortality did not differ between the patients and the controls (RR, 1.08; 95% CI, 0.94-1.25). The type of treatment did not affect the overall risk of cancer (hazard ratio for RAI vs thyroidectomy, 1.03; 95% CI, 0.86-1.23) or cancer mortality (hazard ratio, 1.04; 95% CI, 0.91-1.21). CONCLUSIONS: In this cohort of Finnish patients with hyperthyroidism treated with thyroidectomy or RAI, the overall risk of cancer was not increased, although an increased risk of gastric and respiratory tract cancers was seen in hyperthyroid patients. Based on this large-scale, long-term follow-up study, the increased cancer risk in hyperthyroid patients is attributable to hyperthyroidism and shared risk factors, not the treatment modality. PMID- 26262434 TI - Substrate-Competitive Activity-Based Profiling of Ester Prodrug Activating Enzymes. AB - Understanding the mechanistic basis of prodrug delivery and activation is critical for establishing species-specific prodrug sensitivities necessary for evaluating preclinical animal models and potential drug-drug interactions. Despite significant adoption of prodrug methodologies for enhanced pharmacokinetics, functional annotation of prodrug activating enzymes is laborious and often unaddressed. Activity-based protein profiling (ABPP) describes an emerging chemoproteomic approach to assay active site occupancy within a mechanistically similar enzyme class in native proteomes. The serine hydrolase enzyme family is broadly reactive with reporter-linked fluorophosphonates, which have shown to provide a mechanism-based covalent labeling strategy to assay the activation state and active site occupancy of cellular serine amidases, esterases, and thioesterases. Here we describe a modified ABPP approach using direct substrate competition to identify activating enzymes for an ethyl ester prodrug, the influenza neuraminidase inhibitor oseltamivir. Substrate-competitive ABPP analysis identified carboxylesterase 1 (CES1) as an oseltamivir-activating enzyme in intestinal cell homogenates. Saturating concentrations of oseltamivir lead to a four-fold reduction in the observed rate constant for CES1 inactivation by fluorophosphonates. WWL50, a reported carbamate inhibitor of mouse CES1, blocked oseltamivir hydrolysis activity in human cell homogenates, confirming CES1 is the primary prodrug activating enzyme for oseltamivir in human liver and intestinal cell lines. The related carbamate inhibitor WWL79 inhibited mouse but not human CES1, providing a series of probes for analyzing prodrug activation mechanisms in different preclinical models. Overall, we present a substrate-competitive activity-based profiling approach for broadly surveying candidate prodrug hydrolyzing enzymes and outline the kinetic parameters for activating enzyme discovery, ester prodrug design, and preclinical development of ester prodrugs. PMID- 26262436 TI - Bone Marrow Function After (131)I Therapy in Patients With Differentiated Thyroid Carcinoma. AB - OBJECTIVE: The primary objective was to evaluate the short- and long-term toxic effects of radioiodine ((131)I) therapy on bone marrow function in differentiated thyroid carcinoma (DTC) patients. The secondary objective was to define characteristics of patients at risk for impaired bone marrow function after (131)I treatment. PATIENTS AND METHODS: DTC patients treated with (131)I between 1989 and 2013 were included. We excluded patients with morbidities or treatments that could have influenced blood count parameters. Baseline platelets, leukocytes, and hemoglobin levels were compared with blood counts at 3 and 6 months and at 1 and 5 years after treatment. Logistic multivariate regression analyses were performed to determine patient characteristics associated with thrombocytopenia. RESULTS: We included 331 patients. Mean +/- SD age was 47.5 +/- 17.2 years, and 74.0% were female. Posttreatment platelets were significantly decreased at 6 months and 1 year, as compared with baseline. Leukocyte counts were also decreased at 3 and 6 months and at 1 year after treatment. No decreases in hemoglobin were found. Five years after treatment, platelet and leukocyte counts were comparable with baseline. Fourteen patients (4.2%) developed transient posttreatment thrombocytopenia. Risk factors for thrombocytopenia were older age, T4 tumor stage, male gender, and cumulative dose (131)I. After a multivariate regression analysis, the cumulative dose (131)I remained independently associated with thrombocytopenia. CONCLUSION: Posttreatment platelets and leukocytes were transiently decreased compared with pretreatment values in a general DTC population. Cumulative (131)I dose was independently associated with thrombocytopenia. Platelets and leukocytes normalized to baseline levels 5 years after treatment, implying that in most patients the clinical effects of bone marrow toxicity are limited. PMID- 26262437 TI - Diagnosis of Primary Hypophysitis in Germany. AB - CONTEXT: Representative data on diagnostic findings in primary hypophysitis (PrHy) are scarce. OBJECTIVE: The objective of the study was to collate consistent data on clinical features in a large series of patients with PrHy. Another objective was to gain information on current practice in a diagnostic work-up. DESIGN: The Pituitary Working Group of the German Society of Endocrinology conducted a nationwide retrospective cross-sectional cohort study in Germany. PATIENTS: Seventy-six patients with PrHy were identified. MAIN OUTCOME MEASURES: Clinical and endocrinological features were assessed. RESULTS: Headache (50%) and increase in body mass (18%) were the most frequent nonendocrine symptoms. Hypophysitis was associated with pregnancy in only 11% of the female patients. Diabetes insipidus was found in 54% of the patients at presentation. Hypogonadotropic hypogonadism was the most frequent endocrine failure (62%), whereas GH deficiency was the least frequent (37%). With 86%, thickening of the pituitary stalk was the prevailing neuroradiological sign. Compared with surgical cases, the cases without histological confirmation presented more often with suprasellar lesions and had less severe nonendocrine symptoms. Granulomatous hypophysitis was associated with more severe clinical symptoms than lymphocytic hypophysitis. Examination of cerebrospinal fluid was predominantly performed in participating neurosurgical centers, whereas thyroid antibodies were almost exclusively assessed in endocrinological centers. CONCLUSION: In contrast to the literature, hypogonadism was found to be the most frequent endocrine failure in PrHy. Weight gain was identified as a clinical sign of PrHy. In the majority of patients, PrHy can be reliably identified by characteristic clinical signs and symptoms, obviating histological confirmation. The diagnostic approach should be standardized in PrHy. PMID- 26262438 TI - Normal Thyroid Function and the Risk of Atrial Fibrillation: the Rotterdam Study. AB - CONTEXT: Hyperthyroidism is an established risk factor for atrial fibrillation (AF), but information concerning the association with variations within the normal range of thyroid function and subgroups at risk is lacking. OBJECTIVE: This study aimed to investigate the association between normal thyroid function and AF prospectively and explore potential differential risk patterns. DESIGN, SETTING, AND PARTICIPANTS: From the Rotterdam Study we included 9166 participants >= 45 y with TSH and/or free T4 (FT4) measurements and AF assessment (1997-2012 median followup, 6.8 y), with 399 prevalent and 403 incident AF cases. MAIN OUTCOME MEASURES: Outcome measures were 3-fold: 1) hazard ratios (HRs) for the risk of incident AF by Cox proportional-hazards models, 2) 10-year absolute risks taking competing risk of death into account, and 3) discrimination ability of adding FT4 to the CHARGE-AF simple model, an established prediction model for AF. RESULTS: Higher FT4 levels were associated with higher risks of AF (HR 1.63, 95% confidence interval, 1.19-2.22), when comparing those in the highest quartile to those in lowest quartile. Absolute 10-year risks increased with higher FT4 in participants <= 65 y from 1-9% and from 6-12% in subjects >= 65 y. Discrimination of the prediction model improved when adding FT4 to the simple model (c statistic, 0.722 vs 0.729; P = .039). TSH levels were not associated with AF. CONCLUSIONS: There is an increased risk of AF with higher FT4 levels within the normal range, especially in younger subjects. Adding FT4 to the simple model slightly improved discrimination of risk prediction. PMID- 26262440 TI - Fluoroquinolones and Tetracycline Antibiotics in a Portuguese Aquaculture System and Aquatic Surroundings: Occurrence and Environmental Impact. AB - The growth of aquaculture over the past few years is widely recognized as one of the main sources of antibiotics, mainly fluoroquinolones (FQ) and tetracyclines (TC), in the aquatic environment, consequently, increasing the risk of the emergence of antibiotic bacterial resistance and promoting the spread of resistant genes. This study aimed to (1) develop and validate a multiresidue method for determination and quantification of ciprofloxacin (CIP), difloxacin (DIFL), enrofloxacin (ENR), norfloxacin (NOR), sarafloxacin (SARA), and oxytetracycline (OXY) in aquaculture waters and surrounding water bodies and (2) provide the first Portuguese data to utilize in assessment of risk of adverse effects. In addition, the potential environmental impact posed by these antibiotics to aquatic organisms, belonging to different trophic levels, when exposed to the studied aquaculture waters was also assessed. The analytical strategy comprised of solid-phase extraction (SPE) through Oasis HLB cartridges, and detection and quantification by liquid chromatography with tandem mass spectrometry (LC/MS(n)). Method detection limits (MDL) and method quantification limits (MQL) were in the range of 0.7-3 ng/L and 2.4-10 ng/L, respectively. Recoveries varied between 57.4 and 122.8%. The method was applied to 31 water samples collected from an aquaculture and surrounding water bodies located in north of Portugal. Residues of all antibiotics, except SARA and DIFL, were detected at concentrations ranging from 3 to 75.1 ng/L. Norfloxacin was the antibiotic present at highest frequency and concentration. Regarding the environmental impact assessment (EIA), a risk quotient higher than 1 was observed for NOR. PMID- 26262439 TI - Identification of dengue viral RNA-dependent RNA polymerase inhibitor using computational fragment-based approaches and molecular dynamics study. AB - Dengue is a major public health concern in tropical and subtropical countries of the world. There are no specific drugs available to treat dengue. Even though several candidates targeted both viral and host proteins to overcome dengue infection, they have not yet entered into the later stages of clinical trials. In order to design a drug for dengue fever, newly emerged fragment-based drug designing technique was applied. RNA-dependent RNA polymerase, which is essential for dengue viral replication is chosen as a drug target for dengue drug discovery. A cascade of methods, fragment screening, fragment growing, and fragment linking revealed the compound [2-(4-carbamoylpiperidin-1-yl)-2 oxoethyl]8-(1,3-benzothiazol-2-yl)naphthalene-1-carboxylate as a potent dengue viral polymerase inhibitor. Both strain energy and binding free energy calculations predicted that this could be a better inhibitor than the existing ones. Molecular dynamics simulation studies showed that the dengue polymerase lead complex is stable and their interactions are consistent throughout the simulation. The hydrogen-bonded interactions formed by the residues Arg792, Thr794, Ser796, and Asn405 are the primary contributors for the stability and the rigidity of the polymerase-lead complex. This might keep the polymerase in closed conformation and thus inhibits viral replication. Hence, this might be a promising lead molecule for dengue drug designing. Further optimization of this lead molecule would result in a potent drug for dengue. PMID- 26262441 TI - Persistent Organochlorine Pesticide Exposure Related to a Formerly Used Defense Site on St. Lawrence Island, Alaska: Data from Sentinel Fish and Human Sera. AB - St. Lawrence Island, Alaska, is the largest island in the Bering Sea, located 60 km from Siberia. The island is home to approximately 1600 St. Lawrence Island Yupik residents who live a subsistence way of life. Two formerly used defense sites (FUDS) exist on the island, one of which, Northeast Cape, has been the subject of a $123 million cleanup effort. Environmental monitoring demonstrates localized soil and watershed contamination with polychlorinated biphenyls (PCB), organochlorine (OC) pesticides, mercury, and arsenic. This study examined whether the Northeast Cape FUDS is a source of exposure to OC pesticides. In total, 71 serum samples were collected during site remediation from volunteers who represented three geographic regions of the island. In addition, ninespine stickleback (Pungitius pungitius) and Alaska blackfish (Dallia pectoralis) were collected from Northeast Cape after remediation to assess continuing presence of OC pesticides. Chlordane compounds, DDT compounds, mirex, and hexachlorobenzene (HCB) were the most prevalent and present at the highest concentrations in both fish tissues and human serum samples. After controlling for age and gender, activities near the Northeast Cape FUDS were associated with an increase in serum HCB as compared to residents of the farthest village from the site. Positive but nonsignificant relationships for sum-chlordane and sum-DDT were also found. Organochlorine concentrations in fish samples did not show clear geographic trends, but appear elevated compared to other sites in Alaska. Taken together, data suggest that contamination of the local environment at the Northeast Cape FUDS may increase exposure to select persistent OC pesticides. PMID- 26262443 TI - Determination of Selected Phthalates by Gas Chromatography-Mass Spectrometry in Personal Perfumes. AB - A simple and fast method is proposed to analyze commercial personal perfumes. Our method includes measurement of phthalates, known to be major sources of endocrine disruptor chemicals (EDC), which originate from the less volatile fraction of perfumes. The quantification of phthalates were carried out directly with no sample preparation required on 30 samples of commercial products using gas chromatography and mass spectrometry (GC-MS) as a detector. The total concentrations of 15 investigated compounds ranged from 17 to 9650 mg/L with an average of 2643 mg/L. The highest total concentration was found in cologne. Diethyl phthalate (DEP), diisobutyl phthalate (DiBP), di(2-ethylhexyl) phthalate (DEHP), and di-n-butyl phthalate (DBP) were detected in appreciable concentrations. Further, it was found that the composition of counterfeit samples varied widely from that of authentic products. The composition of old products was different from that of recent perfumes, which contain less harmful chemicals, attributed to the ban on some phthalates in Europe due their toxicity. It should be noted that older and contaminated products are not equivalent to authentic products when considering quality, safety, and probably effectiveness. Older and nonapproved perfumes contain chemicals that are not allowed for commercial use and may contain toxic impurities. PMID- 26262442 TI - Chronic Responses of Daphnia magna Under Dietary Exposure to Leaves of a Transgenic (Event MON810) Bt-Maize Hybrid and its Conventional Near-Isoline. AB - Insect resistance is the second most common trait globally in cultivated genetically modified (GM) plants. Resistance is usually obtained by introducing into the plant's genome genes from the bacterium Bacillus thuringiensis (Bt) coding for insecticidal proteins (Cry proteins or toxins) that target insect pests. The aim of this study was to examine the hypothesis that a chronic, high dose dietary exposure to leaves of a Bt-maize hybrid (GM event MON810, expressing a transgenic or recombinant Cry1Ab toxin), exerted no adverse effects on fitness parameters of the aquatic nontarget organism Daphnia magna (water flea) when compared to an identical control diet based on leaves of the non-GM near-isoline. Cry1Ab was immunologically detected and quantified in GM maize leaf material used for Daphnia feed. A 69-kD protein near Bt's active core-toxin size and a 34-kD protein were identified. The D. magna bioassay showed a resource allocation to production of resting eggs and early fecundity in D. magna fed GM maize, with adverse effects for body size and fecundity later in life. This is the first study to examine GM-plant leaf material in the D. magna model, and provides of negative fitness effects of a MON810 maize hybrid in a nontarget model organism under chronic, high dietary exposure. Based upon these results, it is postulated that the observed transgenic proteins exert a nontarget effect in D. magna and/or unintended changes were produced in the maize genome/metabolome by the transformation process, producing a nutritional difference between GM-maize and non-GM near-isoline. PMID- 26262444 TI - Oxidative Stress Induced by Cigarette Smoke Extracts in Human Brain Cells (T98G) and Human Brain Microvascular Endothelial Cells (HBMEC) in Mono- and Co-Culture. AB - The objective of the current study was to examine oxidative stress induced by cigarette smoke extract (CSE) or cigarette smoke condensate (CSC) in human brain cells (T98G) and human brain microvascular endothelial cells (HBMEC) in mono- and co-culture systems. Cell viability of T98G cells exposed to CSC (0.05-4 mg/ml) was significantly decreased compared to CSE (0.025-20%). There were no marked differences between quantities of reactive oxygen species (ROS) generation by either CSE (2, 4, and 10%) or CSC (0.2, 0.4, and 0.8 mg/ml) treatment compared to control. However, a significant effect was noted in ROS generation following CSC incubation at 4mg/ml. Cellular integrity of HBMEC decreased to 74 and 64% within 120 h of exposure at the IC50 value of CSE and CSC, respectively. This study suggests that chronic exposure to cigarette smoking might initiate damage to the blood-brain barrier. PMID- 26262445 TI - Safe percutaneous endoscopic colostomy for severe constipation with use of the introducer method. PMID- 26262446 TI - Gastroscopic removal of intrahepatic stones through a large choledochoduodenal fistula. PMID- 26262447 TI - Esophageal hematoma after peroral endoscopic myotomy for achalasia in a patient on antiplatelet therapy. PMID- 26262448 TI - A novel method for closure of a choledochoduodenostomy in sump syndrome. PMID- 26262449 TI - Endoscopic ultrasound diagnosis of a primary hepatoid carcinoma of the pancreas. PMID- 26262450 TI - Higher Quality of Care and Patient Safety Associated With Better NICU Work Environments. AB - The objective of this study was to investigate the associations between the neonatal intensive care unit (NICU) work environment, quality of care, safety, and patient outcomes. A secondary analysis was conducted of responses of 1247 NICU staff nurses in 171 hospitals to a large nurse survey. Better work environments were associated with lower odds of nurses reporting poor quality, safety, and outcomes. Improving the work environment may be a promising strategy to achieve safer settings for at-risk newborns. PMID- 26262451 TI - The Significance of Mismatch Repair Deficiency in Young Patients With Endometrial Cancer. AB - The objective of this study was to identify the tumor characteristics associated with mismatch repair deficiency in young patients with endometrial carcinoma. Young patients (45 yr old or younger) with endometrial carcinoma treated by hysterectomy in our institution between July 2001 and June 2009 were identified. The clinical and pathologic data were obtained by review of clinical records. Among the 122 cases identified, paraffin sections were available in 67 cases for immunohistochemical staining and frozen tissue available in 62 cases for microsatellite instability (MSI) analysis. Both paraffin sections and frozen tissue were available in 36 cases. Among the 67 cases with immunohistochemical staining, 22 (32.8%) showed loss of expression of at least 1 mismatch repair protein. Defective MLH1 or MSH2 expression was associated with poor prognostic factors, including a higher incidence of pelvic lymph nodes metastasis (P=0.018) and higher stage (P=0.022) for MLH1, and an increased risk of lymphovascular permeation (P=0.015) for MSH2. On the contrary, defective MSH6 protein expression was associated with a lower incidence of high-grade tumors (P=0.04). Among the 62 cases with MSI analysis, 12 (19.4%) tumors were classified as microsatellite-high (MSI-H), whereas 2 (3.2%) were classified as microsatellite-low (MSI-L). There was no difference in the pathologic characteristics between MSI-stable and MSI-H tumor. We concluded that defective mismatch repair expression is important in young patients with endometrial carcinoma, with MSH6 protein being most commonly affected. The phenotype resulting from defective MSH6 expression was different from that caused by MLH1 or MSH2 loss. PMID- 26262452 TI - Inflammatory Myofibroblastic Tumor of the Placenta: A Report of a Novel Lesion in 2 Patients. AB - Inflammatory myofibroblastic tumor has been described in a wide variety of anatomic sites, although in the gynecologic tract, it has mostly been documented in the uterus, and has never been described in the placenta. Two patients presented with well-circumscribed placental masses that showed classic histologic features of inflammatory myofibroblastic tumor including a proliferation of myofibroblastic cells, a mixed inflammatory infiltrate, and a myxoid background. One case was positive by immunohistochemistry for anaplastic lymphoma kinase (ALK 1), whereas the other was negative by immunohistochemistry and fluorescent in situ hybridization. Inflammatory myofibroblastic tumors should be differentiated from other more aggressive uterine tumors that may involve the placenta by direct extension/metastasis because they can be managed conservatively, and in these 2 cases, did not seem to affect the course of the patient's pregnancies. PMID- 26262453 TI - Missed Initial Diagnosis of Malignant Struma Ovarii Containing Follicular Thyroid Carcinoma: Metastatic Pulmonary Recurrence 17 yr After Ovariectomy. AB - Distant metastasis of rare malignant struma ovarii (MSO) has been reported for cases associated with papillary thyroid cancer but few with follicular thyroid cancer. A 38-yr-old woman with struma ovarii that was initially diagnosed as "benign" presented with pulmonary metastasis and coughing 17 yr later. The lungs lesions were confirmed to be follicular thyroid cancer by biopsy. Rereview of the initial surgical ovary specimens confirmed the condition to be MSO with follicular thyroid cancer. The patient was treated with total thyroidectomy, which showed no thyroid malignancy, followed by (131)I (iodine-131) treatments. Dramatic reduction was observed in both the stimulated thyroglobulin level and the size of the pulmonary metastases over 1 yr. During the following 3-yr follow up, the patient remained clinically well, with undetectable thyroglobulin (<1 ng/mL) and small stable pulmonary lesions. This is an exceedingly rare case of MSO with follicular thyroid cancer metastasized to the lungs presenting with a late onset but a fortunate excellent response to multidiscipline treatments. It is advisable that struma ovarii be carefully examined to avoid missing malignancy and patients be clinically followed up even with a benign initial diagnosis. PMID- 26262454 TI - Growing Teratoma Syndrome: A Report of 2 Cases and Review of the Literature. AB - We report 2 cases of growing teratoma syndrome (GTS) in patients who had been treated with surgery and chemotherapy for immature ovarian teratoma. One of the patients presented with probable paraneoplastic encephalitis. Resection of "recurrences" in both patients showed deposits of mature teratoma and extensive gliomatosis peritonei. It is important for both pathologists and clinicians to be aware of this uncommon entity to avoid misdiagnosis of GTS as recurrence of immature teratoma and disease progression, and to avert unnecessary continuation of chemotherapy. GTS may occur several years after diagnosis of the primary tumor, and rarely develop in treated patients who have become pregnant. Surgical debulking is the optimal modality of treatment as GTS is not chemosensitive. If surgical debulking of GTS is incomplete, long-term follow-up with imaging is required to avoid complications such as bowel obstruction and the sequelae of pressure effects (such as vascular thrombosis, fistula formation, etc.) from bulky deposits of mature teratoma/GTS and gliomatosis peritonei. PMID- 26262455 TI - Suicide risk assessment in high-risk adolescents. AB - A significant number of adolescents experience depression and other mental health disorders that may put them at risk for suicide. Mental health assessment is an important component of primary healthcare. Depression and suicide risk screening can assist healthcare providers in preventing suicides. PMID- 26262456 TI - Pediatric small bowel transplantation. AB - PURPOSE OF REVIEW: Intestine has become a transplantable organ due to the improvement in immunosuppressive drugs. The early referral to a reference unit is crucial in prognosis. There are still some pending issues like chronic rejection, the knowledge of the role of DSA development or early noninvasive detection of acute rejection. RECENT FINDINGS: The appearance of tacrolimus and mTOR, and the use of induction therapy have marked a turning point with better graft and patient survival rates. The inclusion of the liver in the graft seems to have a protective effect. Surveillance of opportunistic infections has also contributed to improved results. Infection, post-transplant lymphoproliferative disease, rejection and GVHD have still a major role in survival; however, antibody mediated rejection has gained increased attention. SUMMARY: Parenteral nutrition remains the main therapeutic resource in the management of intestinal failure, but intestinal transplant is a therapeutic option when this therapy has failed. Finding the balanced immunosuppression that minimizes risk of rejection while preventing occurrence of complications like post-transplant lymphoproliferative disease or GVHD is an ongoing challenge. The current survival rates of intestinal transplantation are similar to other solid organ transplant. PMID- 26262457 TI - Pulmonary hypertension in potential heart transplant recipients: current treatment strategies. AB - PURPOSE OF REVIEW: Pulmonary hypertension associated with left heart disease is the most commonly encountered form of pulmonary hypertension and is associated with a poor prognosis. As the global burden of heart failure grows, this associated disease can be a major impediment to those patients undergoing cardiac transplantation, given its association with post-transplant right ventricular failure. Unfortunately, the pathophysiology of pulmonary hypertension secondary to left heart failure remains poorly understood, thereby rendering targeted treatment strategies largely undefined. In this review, we provide a review of the currently available literature in this unique patient population. RECENT FINDINGS: The current focus on better defining the underlying pathophysiology and standardizing diagnostic and therapeutic approaches to pulmonary hypertension associated with left heart disease need to be interpreted and made applicable in the context of clinical practice. Given the relative paucity of successful, targeted pharmacological options, there is an increasing evidence that device based therapies, used in conjuncture with medical therapy, may help in lowering the pulmonary pressures by causing sustained left ventricular unloading. SUMMARY: Pulmonary hypertension in the context of left heart disease is the most common form of pulmonary hypertension encountered in clinical practice and is associated with worse prognosis in patients being considered for cardiac transplantation. Therapies targeting left ventricular unloading, as well as pulmonary vascular remodeling, are being increasingly studied and used in daily practice. PMID- 26262458 TI - Chronic lung allograft dysfunction: evolving practice. AB - PURPOSE OF REVIEW: Chronic lung allograft dysfunction (CLAD) was recently introduced as an overarching term covering different phenotypes of chronic allograft dysfunction, including obstructive CLAD (bronchiolitis obliterans syndrome), restrictive CLAD (restrictive allograft syndrome) and graft dysfunction due to causes not related to chronic rejection. In the present review, we will highlight the latest insights and current controversies regarding the new CLAD terminology, underlying pathophysiologic mechanisms, diagnostic approach and possible treatment options. RECENT FINDINGS: Different pathophysiological mechanisms are clearly involved in clinically distinct phenotypes of chronic rejection, as is reflected by differences in histology, allograft function and imaging. Therefore, not all CLAD patients may equally benefit from specific therapies. SUMMARY: The recent introduction of CLAD importantly changed the clinical practice in lung transplant recipients. Given the relative low accuracy of the current diagnostic tools, future research should focus on specific biomarkers, more sensitive pulmonary function parameters and imaging techniques for timely CLAD diagnosis and phenotyping. Personalized or targeted therapeutic options for adequate prevention and treatment of CLAD are required. PMID- 26262459 TI - Current indications, strategies, and outcomes with cardiac transplantation for cardiac amyloidosis and sarcoidosis. AB - PURPOSE OF REVIEW: We describe the general strategies for the management of cardiac amyloidosis with particular focus on the use of cardiac transplantation for amyloid cardiomyopathy. Within this article, we highlight recent data regarding the use of combined heart transplant-chemotherapy, use of cardiac transplant in mutant amyloid disease, and underutilization of cardiac transplantation in sarcoidosis. RECENT FINDINGS: Several center experiences have been recently published, describing management strategies in AL amyloid, with focus on timing of chemotherapy as it relates to transplant, and in mutant amyloid in particular. SUMMARY: Outcomes after heart transplantation are typically worse than in patients undergoing heart transplantation for nonamyloid disease. Staged heart transplantation followed by autologous stem cell transplant therapy appears to provide the best long-term outcome for AL amyloid in highly selected patients. Mutant transthyretin amyloidosis is a disorder related to production of abnormal transthyretin protein in the liver. Combined heart/liver transplant has been utilized to treat both the production of the abnormal transthyretin protein and manage the cardiac dysfunction in highly selected patients, with favorable outcomes. Wild-type transthyretin amyloidosis occurs predominantly in older men. Cardiac transplantation can be utilized for highly selected patients. Sarcoidosis with cardiac involvement, unresponsive to immunosuppressive therapy, may be treated successfully with cardiac transplantation. PMID- 26262460 TI - Antibody-mediated rejection. AB - PURPOSE OF REVIEW: Pulmonary antibody-mediated rejection (AMR) while contributing to acute and chronic allograft dysfunction remains a diagnostic and therapeutic challenge. The diagnostic tenets upon which AMR is defined will be reviewed in the light of recent studies. RECENT FINDINGS: The introduction of solid phase assays such as the Luminex platform has provided a wealth of quantitative data on the presence of anti-human leukocyte antigen (HLA) donor-specific antibodies (DSA). Further studies are required to better define the relationship of circulating DSA and activation of proinflammatory immune pathways that result in allograft dysfunction. The limitations of C4d staining in defining AMR are highlighted from recent studies in lung transplantation and from the 2013 Banff meeting on renal transplantation. SUMMARY: The current challenge to the lung transplant community is to agree on a working definition of pulmonary AMR. Only then can we better appreciate the epidemiology, clinical phenotypes, and treatment of AMR. PMID- 26262461 TI - Post-transplant lymphoproliferative disease and other malignancies after pediatric cardiac transplantation: an evolving landscape. AB - PURPOSE OF REVIEW: Post-transplant lymphoproliferative disorders (PTLDs) remain a significant cause of morbidity and mortality after pediatric solid organ transplantation (SOT). PTLD treatment outcomes have improved steadily over the past decade, in large part due to an enhanced understanding of the disease process, newer immunosuppression regimens, and implementation of evolving chemotherapeutic treatment protocols. RECENT FINDINGS: New therapies continue to be employed to treat PTLDs while maintaining normal allograft function in SOT recipients. These include use of immunosuppressant medications with antitumor activity (mammalian target of rapamycin inhibitors), monoclonal antibody therapies, and the advent of cytotoxic T-cell therapy. Treatment methods to render latent Epstein-Barr virus (EBV)-infected tumor cells more susceptible to antiviral agents continue to be investigated. SUMMARY: PTLD remains a significant potential complication after SOT, particularly in pediatric patients who are more likely to be EBV-negative at the time of transplant and subsequently undergo EBV seroconversion. Risk for PTLD may be reduced by employing strategies such as EBV prophylaxis in seronegative patients, minimizing overall intensity of immunosuppression, and utilizing newer agents that have both immunosuppressive and antiproliferative properties. Treatment outcomes for PTLD have steadily improved over the past decade, related in part to the availability of monoclonal antibody therapies and refined chemotherapeutic regimens. PMID- 26262462 TI - Overview of pediatric organ transplantation: current opinion and future perspectives on immunosuppression. AB - PURPOSE OF REVIEW: The main aim of this review is to highlight the current advances and significant challenges associated with pediatric organ transplantation, and to explore future perspectives. RECENT FINDINGS: Pediatric organ transplantation has greatly improved survival and management of pathological conditions resistant to therapeutic interventions in pediatric populations with end-stage organ failure, and is regarded as a treatment of choice. Advent of immunosuppressive therapies has significantly enhanced the care of these patients and graft survival rates, but the long-term risks of these therapeutic interventions are not well recognized and promote numerous challenges particularly in the pediatric population, due to their off-label use and significant adverse effects that may impact growth, skeletal development, and quality of life. Data regarding the safety of these drugs in children are scare due to the lack of randomized clinical trials in this age group, mainly because of issues related to conducting clinical trials in children and to the small number of pediatric transplantation cases per year. SUMMARY: It is important to generate registries of pediatric patients with organ transplantation for conducting observational studies, which might provide information for designing future RCTs and new insights toward improving the survival rates and long-term predictors of response. PMID- 26262463 TI - Pediatric mechanical circulatory support: available devices and outcomes as bridge-to-transplant therapy. AB - PURPOSE OF REVIEW: The use of mechanical circulatory support in children has increased dramatically over the current decade. A review of the pediatric ventricular assist device (VAD) literature is timely and relevant in order to improve outcomes and refine patient selection as new devices become available and current VADs are used in smaller patients. RECENT FINDINGS: Outcomes of pediatric patients bridged to transplant with VAD therapy continue to improve. Patient selection in children continues to be complex as size and anatomy make decision making unique from the adult practice. In addition, device selection and surgical planning are evolving in children. The use of temporary devices for long-term use is an example of an innovative application of current technology. Sensitization and adverse events are important issues that are necessary to understand in order to improve outcomes. The importance of a national registry to help monitor patient outcomes is critical to assessing this highly technological therapy. SUMMARY: There are many implications of improving and expanding durable device use in children. VAD therapy is evolving as a standard of care as a bridge to transplant in children. Continued surveillance of outcomes is critical to improving patient selection and decreasing adverse events in children with advanced heart failure. PMID- 26262464 TI - Expanding the lung donor pool: advancements and emerging pathways. AB - PURPOSE OF REVIEW: The number of patients listed for lung transplantation largely exceeds the number of available transplantable organs because of a shortage of organ donors and a low utilization rate of lungs from those donors who are available. In recent years, novel strategies have been developed to increase the donor lung pool: improved donor management, the use of lungs from donations after cardiac death (DCD), the use of lobar lung living-donors (LLLD) and the use of ex vivo lung perfusion (EVLP) to assess and repair injured donor lungs. RECENT FINDINGS: An adapted donor management strategy could expand the donor pool up to 20%. DCD lung transplant is an increasing part of the donor pool expansion. Outcomes after controlled DCD seem to be similar to donation after brain death. LLLD transplantation has excellent results for small and critically ill patients. EVLP treatment allows for a significant increase in the rate of suitable lungs and represents an optimal platform for lung reconditioning and specific lung therapies. SUMMARY: A significant increase in the number of available lungs for transplantation is expected in the future because of the wider use of lungs from controlled or uncontrolled DCD and LLLD lungs, and with organ-specific EVLP treatment strategies. PMID- 26262466 TI - Retransplantation. AB - PURPOSE OF REVIEW: With a continuously rising number of lung-transplant procedures performed worldwide, there is an increasing demand for pulmonary retransplantation once recipients develop lung allograft dysfunction. Due to the scarcity of donor organs, it is crucial to identify those recipients who benefit most from a retransplant procedure. RECENT FINDINGS: Similar to primary lung transplantation, patients in an elective, ambulatory status with chronic lung allograft dysfunction can expect the best outcome. Recently, refinements in the sub-selection of this patient group have been established, and during the past years, survival after elective retransplantation has clearly improved. Additionally, technical advances in bridging devices have led to the possibility to offer the most appropriate bridging method based on the individual gas exchange and hemodynamic situation of the patient. This includes the recently introduced concept of awake bridging. These advances paved the way to improved bridging success and better post-transplant outcome, which led to increasing interest in bridging patients to retransplant procedures as well. SUMMARY: Patient selection in pulmonary retransplantation is crucial. Patients with obstructive chronic lung allograft dysfunction in an ambulatory setting are the ideal candidates. Awake bridging strategies for acutely deteriorating patients can provide equal outcomes to elective patients. Nevertheless, avoiding the development of chronic lung allograft dysfunction is the primary goal. PMID- 26262467 TI - Carbon Nanotube Synthesis Using Coal Pyrolysis. AB - This study investigates carbon nanotube (CNT) production from coal pyrolysis wherein the output gases are used in a chemical vapor deposition reactor. The carbon products are similar to those using commercial coal gas as feedstock, but coal is a relatively cheaper feedstock compared to high purity source gases. A Gibbs minimization model has been developed to predict the volume percentages of product gases from coal pyrolysis. Methane and carbon monoxide were the largest carbon components of the product stream and thus formed the primary source for CNT synthesis. Both the model and the observations showed that increasing the furnace temperature led to a decrease in the absolute quantities of "useful" product gases, with the optimal temperature between 400 and 500 degrees C. Based on the experimental data, a kinetic rate law for CNT from coal pyrolysis was derived as d[CNT]/dt = K([CO][CH4])(1/2), where K is a function of several equilibrium constants representing various reactions in the CNT formation process. PMID- 26262468 TI - Validation of the Ottawa Ankle Rules for Acute Foot and Ankle Injuries. AB - The original and modified Ottawa Ankle Rules (OARs) were developed as clinical decision rules for use in emergency departments. However, the OARs have not been evaluated as an acute clinical evaluation tool. OBJECTIVE: To evaluate the measures of diagnostic accuracy of the OARs in the acute setting. METHODS: The OARs were applied to all appropriate ankle injuries at 2 colleges (athletics and club sports) and 21 high schools. The outcomes of OARs, diagnosis, and decision for referral were collected by the athletic trainers (ATs) at each of the locations. Contingency tables were created for evaluations completed within 1 h for which radiographs were obtained. From these data the sensitivity, specificity, positive and negative likelihood ratios, and positive and negative predictive values were calculated. RESULTS: The OARs met the criteria for radiographs in 100 of the 124 cases, of which 38 were actually referred for imaging. Based on radiographic findings in an acute setting, the OARs (n = 38) had a high sensitivity (.88) and are good predictors to rule out the presence of a fracture. Low specificity (0.00) results led to a high number of false positives and low positive predictive values (.18). CONCLUSION: When applied during the first hour after injury the OARs significantly overestimate the need for radiographs. However, a negative finding rules out the need to obtain radiographs. It appears the AT's decision making based on the totality of the examination findings is the best filter in determining referral for radiographs. PMID- 26262465 TI - Primary graft dysfunction: lessons learned about the first 72 h after lung transplantation. AB - PURPOSE OF REVIEW: In 2005, the International Society for Heart and Lung Transplantation published a standardized definition of primary graft dysfunction (PGD), facilitating new knowledge on this form of acute lung injury that occurs within 72 h of lung transplantation. PGD continues to be associated with significant morbidity and mortality. This article will summarize the current literature on the epidemiology of PGD, pathogenesis, risk factors, and preventive and treatment strategies. RECENT FINDINGS: Since 2011, several manuscripts have been published that provide insight into the clinical risk factors and pathogenesis of PGD. In addition, several transplant centers have explored preventive and treatment strategies for PGD, including the use of extracorporeal strategies. More recently, results from several trials assessing the role of extracorporeal lung perfusion may allow for much-needed expansion of the donor pool, without raising PGD rates. SUMMARY: This article will highlight the current state of the science regarding PGD, focusing on recent advances, and set a framework for future preventive and treatment strategies. PMID- 26262469 TI - Resolving the Benzophenone DNA-Photosensitization Mechanism at QM/MM Level. AB - Benzophenone, the parent of the diarylketone family, is a versatile compound commonly used as a UV blocker. It may also trigger triplet-based DNA photosensitization. Therefore, benzophenone is involved in DNA photodamage induction. In the absence of experimentally resolved structure, the mechanism of DNA damage production remains elusive. Employing a hybrid quantum mechanics/molecular mechanics approach, here we address the spin transfer mechanism between this drug and proximal thymine, that is, the DNA nucleobase most prone to suffer triplet damages. PMID- 26262470 TI - Mutual Exclusion of Urea and Trimethylamine N-Oxide from Amino Acids in Mixed Solvent Environment. AB - We study the solvation of amino acids in pure-osmolyte and mixed-osmolyte urea and trimethylamine N-oxide (TMAO) solutions using molecular dynamics simulations. Analysis of Kirkwood-Buff integrals between the solution components provides evidence that in the mixed osmolytic solution, both urea and TMAO are mutually excluded from the amino acid surface, accompanied by an increase in osmolyte osmolyte aggregation. Similar observations are made in simulations of a model protein backbone, represented by triglycine, and suggest that TMAO stabilizes proteins under urea denaturation conditions by effectively removing urea from the protein surface. The effects of the mixed osmolytes on the solvation of the amino acids and the backbone are found to be highly nonlinear in terms of the effects of the individual osmolytes and independent of differences in the strength of the TMAO-water interactions, as observed with different TMAO force fields. PMID- 26262471 TI - Bias-Switchable Permselectivity and Redox Catalytic Activity of a Ferrocene Functionalized, Thin-Film Metal-Organic Framework Compound. AB - The installation of ferrocene molecules within the wide-channel metal-organic framework (MOF) compound, NU-1000, and subsequent configuration of the modified MOF as thin-film coatings on electrodes renders the MOF electroactive in the vicinity of the ferrocenium/ferrocene (Fc(+)/Fc) redox potential due to redox hopping between anchored Fc(+/0) species. The observation of effective site-to site redox hopping points to the potential usefulness of the installed species as a redox shuttle in photoelectrochemical or electrocatalytic systems. At low supporting electrolyte concentration, we observe bias-tunable ionic permselectivity; films are blocking toward solution cations when the MOF is in the ferrocenium form but permeable when in the ferrocene form. Additionally, with ferrocene-functionalized films, we observe that the MOF's pyrene-based linkers, which are otherwise reversibly electroactive, are now redox-silent. Linker electroactivity is fully recovered, however, when the electrolyte concentration is increased 10-fold, that is, to a concentration similar to or exceeding that of an anchored shuttle molecule. The findings have clear implications for the design and use of MOF-based sensors, electrocatalysts, and photoelectrochemical devices. PMID- 26262472 TI - Stable Solar-Driven Water Oxidation to O2(g) by Ni-Oxide-Coated Silicon Photoanodes. AB - Semiconductors with small band gaps (<2 eV) must be stabilized against corrosion or passivation in aqueous electrolytes before such materials can be used as photoelectrodes to directly produce fuels from sunlight. In addition, incorporation of electrocatalysts on the surface of photoelectrodes is required for efficient oxidation of H2O to O2(g) and reduction of H2O or H2O and CO2 to fuels. We report herein the stabilization of np(+)-Si(100) and n-Si(111) photoanodes for over 1200 h of continuous light-driven evolution of O2(g) in 1.0 M KOH(aq) by an earth-abundant, optically transparent, electrocatalytic, stable, conducting nickel oxide layer. Under simulated solar illumination and with optimized index-matching for proper antireflection, NiOx-coated np(+)-Si(100) photoanodes produced photocurrent-onset potentials of -180 +/- 20 mV referenced to the equilibrium potential for evolution of O2(g), photocurrent densities of 29 +/- 1.8 mA cm(-2) at the equilibrium potential for evolution of O2(g), and a solar-to-O2(g) conversion figure-of-merit of 2.1%. PMID- 26262473 TI - Directionality of Double-Bond Photoisomerization Dynamics Induced by a Single Stereogenic Center. AB - In light-driven single-molecule rotary motors, the photoisomerization of a double bond converts light energy into the rotation of a moiety (the rotor) with respect to another (the stator). However, at the level of a molecular population, an effective rotary motion can only be achieved if a large majority of the rotors rotate in the same, specific direction. Here we present a quantitative investigation of the directionality (clockwise vs counterclockwise) induced by a single stereogenic center placed in allylic position with respect to the reactive double bond of a model of the biomimetic indanylidene-pyrrolinium framework. By computing ensembles of nonadiabatic trajectories at 300 K, we predict that the photoisomerization is >70% unidirectional for the Z -> E and E -> Z conversions. Most importantly, we show that such directionality, resulting from the asymmetry of the excited state force field, can still be observed in the presence of a small (ca. 2 degrees ) pretwist or helicity of the reactive double bond. This questions the validity of the conjecture that a significant double-bond pretwist (e.g., >10 degrees ) in the ground state equilibrium structure of synthetic or natural rotary motors would be required for unidirectional motion. PMID- 26262474 TI - In Situ Transmission Electron Microscopy of Cadmium Selenide Nanorod Sublimation. AB - In situ electron microscopy is used to observe the morphological evolution of cadmium selenide nanorods as they sublime under vacuum at a series of elevated temperatures. Mass loss occurs anisotropically along the nanorod's long axis. At temperatures close to the sublimation threshold, the phase change occurs from both tips of the nanorods and proceeds unevenly with periods of rapid mass loss punctuated by periods of relative stability. At higher temperatures, the nanorods sublime at a faster, more uniform rate, but mass loss occurs from only a single end of the rod. We propose a mechanism that accounts for the observed sublimation behavior based on the terrace-ledge-kink (TLK) model and how the nanorod surface chemical environment influences the kinetic barrier of sublimation. PMID- 26262475 TI - Role of Excess Electrons in Nonlinear Optical Response. AB - The excess electron is a kind of special anion with dispersivity, loosely bounding and with other fascinating features, which plays a pivotal role (promote to about 10(6) times in (H2O)3{e}) in the large first hyperpolarizabilities (beta0) of dipole-bound electron clusters. This discovery opens a new perspective on the design of novel nonlinear optical (NLO) molecular materials for electro optic device application. Significantly, doping alkali metal atoms in suitable complexants was proposed as an effective approach to obtain electride and alkalide molecules with excess electron and large NLO responses. The first hyperpolarizability is related to the characteristics of complexants and the excess electron binding states. Subsequently, a series of new strategies for enhancing NLO response and electronic stability of electride and alkalide molecules are exhibited by using various complexants. These strategies include not only the behaviors of pushed and pulled electron, size, shape, and number of coordination sites of complexants but also the number and spin state of excess electrons in these unusual NLO molecules. PMID- 26262476 TI - Emerging Carbon and Post-Carbon Nanomaterial Inks for Printed Electronics. AB - Carbon and post-carbon nanomaterials present desirable electrical, optical, chemical, and mechanical attributes for printed electronics, offering low-cost, large-area functionality on flexible substrates. In this Perspective, recent developments in carbon nanomaterial inks are highlighted. Monodisperse semiconducting single-walled carbon nanotubes compatible with inkjet and aerosol jet printing are ideal channels for thin-film transistors, while inkjet, gravure, and screen-printable graphene-based inks are better-suited for electrodes and interconnects. Despite the high performance achieved in prototype devices, additional effort is required to address materials integration issues encountered in more complex systems. In this regard, post-carbon nanomaterial inks (e.g., electrically insulating boron nitride and optically active transition-metal dichalcogenides) present promising opportunities. Finally, emerging work to extend these nanomaterial inks to three-dimensional printing provides a path toward nonplanar devices. Overall, the superlative properties of these materials, coupled with versatile assembly by printing techniques, offer a powerful platform for next-generation printed electronics. PMID- 26262477 TI - Coherent Exciton Dynamics in the Presence of Underdamped Vibrations. AB - Recent ultrafast optical experiments show that excitons in large biological light harvesting complexes are coupled to molecular vibration modes. These high frequency vibrations will not only affect the optical response, but also drive the exciton transport. Here, using a model dimer system, the frequency of the underdamped vibration is shown to have a strong effect on the exciton dynamics such that quantum coherent oscillations in the system can be present even in the case of strong noise. Two mechanisms are identified to be responsible for the enhanced transport efficiency: critical damping due to the tunable effective strength of the coupling to the bath, and resonance coupling where the vibrational frequency coincides with the energy gap in the system. The interplay of these two mechanisms determines parameters responsible for the most efficient transport, and these optimal control parameters are comparable to those in realistic light-harvesting complexes. Interestingly, oscillations in the excitonic coherence at resonance are suppressed in comparison to the case of an off-resonant vibration. PMID- 26262478 TI - Huge Quantum Symmetry Effect in the O + O2 Exchange Reaction. AB - We report extensive, full quantum-mechanical calculations for the (16)O + (16)O(16)O -> (16)O(16)O + (16)O collisions, for both inelastic and atom exchange processes, using a time-independent method based on hyperspherical coordinates. The rates obtained in the present study are much larger than the previously reported ones for this system. The discrepancy is attributed to a huge symmetry effect that was missing in the studies so far. This effect differs from the well known isotope effect. Importance of this quantum effect is further confirmed by comparison with results for the (16)O + (18)O(18)O -> (16)O(18)O + (18)O, exchange reaction. PMID- 26262479 TI - Vibrational State-Selective Resonant Two-Photon Photoelectron Spectroscopy of AuS(-) via a Spin-Forbidden Excited State. AB - Vibrational state-selective resonant two-photon photoelectron spectra have been obtained via a triplet intermediate state ((3)Sigma(-)) of AuS(-) near its detachment threshold using high-resolution photoelectron imaging of cryogenically cooled AuS(-) anions. Four vibrational levels of the (3)Sigma(-) excited state are observed to be below the detachment threshold. Resonant two-photon absorptions through these levels yield vibrational state-selective photoelectron spectra to the (2)Sigma final state of neutral AuS with broad and drastically different Franck-Condon distributions, reflecting the symmetries of the vibrational wave functions of the (3)Sigma(-) intermediate state. The (3)Sigma(-) excited state is spin-forbidden from the (1)Sigma(+) ground state of AuS(-) and is accessed due to strong relativistic effects. The nature of the (3)Sigma(-) excited state is confirmed by angular distributions of the photoelectron images and quantum calculations. PMID- 26262480 TI - Direct Coherent Raman Temperature Imaging and Wideband Chemical Detection in a Hydrocarbon Flat Flame. AB - A single-shot coherent Raman imaging technique has been developed for spatially correlated one-dimensional high-fidelity gas-phase thermometry and multiplex chemical detection in flames. The technique utilizes two-beam phase matching, operating a single ultrashort pump/Stokes excitation pulse (7 fs) and a narrowband picosecond probe pulse (70 ps), interrogating a Raman active window of ~4200 cm(-1) with ~0.3 cm(-1) spectral resolution. The measurement geometry is formed intersecting the two beams shaped as laser-sheets and the one-coordinate spatial information is retrieved with a linespread function of <40 MUm. The advance provides the possibility for the multiplexed measurement of all combustion relevant major species simultaneously with gaseous temperature monitored over a several millimeter field of view. The current technique is optimized in a premixed hydrocarbon flat-flame. At the flame-front, it is shown that direct imaging renders the temperature profile within ~1% inaccuracy, whereas typical point-wise raster scanning may have relative systematic deviations up to 15% due to spatial averaging effects. PMID- 26262481 TI - Electromechanical Signatures for DNA Sequencing through a Mechanosensitive Nanopore. AB - Biological nanopores have been extensively used for DNA base detection since these pores are widely available and tunable through mutations. Distinguishing bases of nucleic acids by passing them through nanopores has so far primarily relied on electrical signals-specifically, ionic currents through the nanopores. However, the low signal-to-noise ratio makes detection of ionic currents difficult. In this study, we show that the initially closed mechanosensitive channel of large conductance (MscL) protein pore opens for single-stranded DNA (ssDNA) translocation under an applied electric field. As each nucleotide translocates through the pore, a unique mechanical signal is observed specifically, the tension in the membrane containing the MscL pore is different for each nucleotide. In addition to the membrane tension, we found that the ionic current is also different for the four nucleotide types. The initially closed MscL adapts its opening for nucleotide translocation due to the flexibility of the pore. This unique operation of MscL provides single nucleotide resolution in both electrical and mechanical signals. Finally, we also show that the speed of DNA translocation is roughly 1 order of magnitude slower in MscL compared to Mycobacterium smegmatis porin A (MspA), suggesting MscL to be an attractive protein pore for DNA sequencing. PMID- 26262482 TI - Self-Assembled 3D Graphene Monolith from Solution. AB - Three-dimensional (3D) graphene-assembled monoliths (GAs), especially ones prepared by self-assembly in the liquid phase, represent promising forms to realize the practical applications of graphene due to their high surface utilization and operability. However, the understanding of the assembly process and structure control of 3D GAs, as a new class of carbon materials, is quite inadequate. In this Perspective, we give a demonstration of the assembly process and discuss the key factors involved in the structure control of 3D GAs to pave the way for their future applications. It is shown that the assembly process starts with the phase separation, which is responsible for the formation of the 3D networked structure and liquid phase as the spacers avoid the parallel overlap of graphene layers and help form an interlinked pore system. Well-tailored graphene sheets and selected assembly media must be a precondition for a well controlled assembly process and microstructure of a 3D GA. The potential applications in energy storage featuring high rate and high volumetric energy density demonstrate advantages of 3D GAs in real applications. PMID- 26262483 TI - Zr Incorporation into TiO2 Electrodes Reduces Hysteresis and Improves Performance in Hybrid Perovskite Solar Cells while Increasing Carrier Lifetimes. AB - We investigate zirconium (Zr) incorporation into the titanium dioxide (TiO2) electron-transporting layer used in organometal halide perovskite photovoltaics. Compared to Zr-free controls, solar cells employing electrodes containing Zr exhibit increased power conversion efficiency (PCE) and decreased hysteresis. We use transient photovoltage and photocurrent extraction to measure carrier lifetimes and densities and observe longer carrier lifetimes and higher charge densities in devices on Zr-containing electrodes at microsecond times as well as longer persistent photovoltages extending from ~milliseconds to tens of seconds. We characterize the surface stoichiometry and change in work function and reduction potential of the TiO2 upon incorporation of Zr and discuss the charge recombination at the TiO2 interface in the context of these variables. Finally, we show that the combination of Zr-TiO2 electrode modification with device pyridine treatment leads to a cumulative improvement in performance. PMID- 26262484 TI - Modulations of Transition-State Control of State-to-State Dynamics in the F + H2O -> HF + OH Reaction. AB - The full-dimensional quantum dynamics of the F + H2O -> HF + OH reaction is investigated at the state-to-state level for the first time using a transition state wave packet method on an accurate global potential energy surface. It is found that the H2O rotation enhances the reactivity and the product-state distribution is dominated by HF vibrational excitation while the OH moiety serves effectively as a spectator. These observations underscore the transition-state control of the reaction dynamics, as both the H2O rotational and HF vibrational modes are strongly coupled to the reaction coordinate at the transition state. It is also shown that the transition-state dominance of the reaction dynamics is modulated by other features on the potential energy surface, such as the prereaction well. PMID- 26262485 TI - Mechanical Origin of the Structural Phase Transition in Methylammonium Lead Iodide CH3NH3PbI3. AB - The methylammonium lead iodide perovskite (MAPbI3) is presently a desirable material for photovoltaic application. Its structure is orthorhombic at low temperature and tetragonal at room temperature. Most theoretical works have focused on either tetragonal or orthorhombic phase alone leaving a gap in the understanding of the structural phase transition in between. In this work, by ab initio calculations, we elucidate the origin of structural phase transition between these two phases. We show that there exists a critical ratio of out-of plane to in-plane lattice constants, c/a ~ 1.45, where at low c/a the orthorhombic Pnma phase is stable while the tetragonal I4/mcm phase is stable at high c/a. Varying the c/a ratio leads to a change of PbI6 octahedral tilting with the rotation of CH3NH3(+) cations about the NH3 component in and out of the Oxy plane. The origin of this rotation is identified. We propose that under epitaxial conditions a gradual change in structural phase of the MAPbI3 perovskite may exist and understanding its electronic properties will be beneficial toward the solar cell community. PMID- 26262486 TI - What Is Hot in Physical Chemistry? PMID- 26262487 TI - Contacts Between Alcohols in Water Are Random Rather than Hydrophobic. AB - Given the importance of water-mediated hydrophobic interactions in a wide range of biological and synthetic self-assembly processes, it is remarkable that both the sign and the magnitude of the hydrophobic interactions between simple amphiphiles, such as alcohols, remain unresolved. To address this question, we have performed Raman hydration-shell vibrational spectroscopy and polarization resolved femtosecond infrared experiments, as well as random mixing and molecular dynamics simulations. Our results indicate that there are no more hydrophobic contacts in aqueous solutions of alcohols ranging from methanol to tertiary butyl alcohol than in random mixtures of the same concentration. This implies that the interaction between small hydrophobic groups is weaker than thermal energy fluctuations. Thus, the corresponding water-mediated hydrophobic interaction must be repulsive, with a magnitude sufficient to negate the attractive direct van der Waals interaction between the hydrophobic groups. PMID- 26262488 TI - Ferroelectric Domain Wall Induced Band Gap Reduction and Charge Separation in Organometal Halide Perovskites. AB - Organometal halide perovskites have been intensely studied in the past 5 years, inspired by their certified high photovoltaic power conversion efficiency. Some of these materials are room-temperature ferroelectrics. The presence of switchable ferroelectric domains in methylammonium lead triiodide, CH3NH3PbI3, has recently been observed via piezoresponse force microscopy. Here, we focus on the structural and electronic properties of ferroelectric domain walls in CH3NH3PbX3 (X = Cl, Br, I). We find that organometal halide perovskites can form both charged and uncharged domain walls due to the flexible orientational order of the organic molecules. The electronic band gaps for domain structures possessing 180 and 90 degrees walls are estimated with density functional theory. It is found that the presence of charged domain walls will significantly reduce the band gap by 20-40%, while the presence of uncharged domain walls has no substantial impact on the band gap. We demonstrate that charged domain walls can serve as segregated channels for the motions of charge carriers. These results highlight the importance of ferroelectric domain walls in hybrid perovskites for photovoltaic applications and suggest a possible avenue for device optimization through domain patterning. PMID- 26262490 TI - Inverting Asymmetric Confinement Potentials in Core/Thick-Shell Nanocrystals. AB - We investigate CdSe/ZnSe core/thick-shell nanocrystals (a.k.a. giant-nanocrystal quantum dots [g-NQDs]) that have an asymmetric electron/hole confinement potential opposite to nonblinking CdSe/CdS g-NQDs. We deconstruct the photon streams into five different photoluminescence (PL) intensity levels and analyze second-order photon correlation (g((2))) traces of each PL intensity level. This analysis allows us to decouple the contribution of exciton charging from the g((2)) experiment and determine the quantum yield of neutral biexciton states to be in the range of ~20-50%, a value comparable to that of CdSe/CdS g-NQDs. We also show that the Auger recombination rate of positive trion states is suppressed compared to that of negative trions. This suppression, however, is shown not to be strong enough to yield complete suppression of PL fluctuations due to the heavy effective mass of holes. Strong intensity fluctuations also result from the fact that hole charging occurs more readily in CdSe/ZnSe g-NQDs than electron charging in CdSe/CdS g-NQDs. PMID- 26262489 TI - Direct Correlation between Ionic Liquid Transport Properties and Ion Pair Lifetimes: A Molecular Dynamics Study. AB - Self-diffusivities as a function of temperature were computed for 29 different ionic liquids (ILs) covering a wide variety of cation and anion classes. Ideal ionic conductivities (sigmaNE) were estimated from the self-diffusivities via the Nernst-Einstein relation. The ion pair (IP) lifetimes (tauIP) and ion cage (IC) lifetimes (tauIC) of each IL were also computed. A linear relationship between the calculated self-diffusivities and the inverse of IP or IC lifetimes was observed. A similar inverse linear relationship was also observed for ideal ionic conductivity. These relationships were found to be independent of temperature and the nature of the IL. These observations connect macroscopic dynamic properties with local atomic-level motions and strongly suggest that the dynamics of ILs are governed by a universal IP or IC forming and breaking mechanism. Thus, in order to design an ionic liquid with enhanced dynamics, one should consider how to minimize IP or IC lifetimes. PMID- 26262491 TI - Indium Oxide-Single-Walled Carbon Nanotube Composite for Ethanol Sensing at Room Temperature. AB - Utilizing a sol-gel synthesis, indium oxide is grown on the surface of oxidized single-walled carbon nanotubes (SWCNT) to form a hybrid material with high conductivity and sensitivity toward certain organic vapors. The room-temperature sensing of dilute ethanol and acetone vapors on the surface of indium oxide/SWCNT hybrid material is studied using electrical conductance experiments in a nonoxidizing environment. Through testing of variously calcinated materials, it was observed that the degree of annealing greatly affects the material's response to acetone and ethanol, such that the intermediate calcination condition yields the best sensitivity. DFT simulations are used to study the interface between defective SWCNT and indium oxide, as well as the interaction between ethanol and acetone molecules with the indium oxide/SWCNT hybrid material. PMID- 26262492 TI - Toward Ratiometric Nanothermometry via Intrinsic Dual Emission from Semiconductor Nanocrystals. AB - Semiconductor nanocrystals have been synthesized that support intrinsic dual emission from the excitonic core as well as the surface. By virtue of chemical control of the thermodynamics of the core/surface equilibria, these nanocrystals support ratiometric temperature sensing over a broad temperature scale. This surface-chemistry-based approach for creating intrinsic dual emission enables a completely new strategy for application of these nanocrystals in optical nanothermometry. PMID- 26262493 TI - Use of Mixed CH3-/HC(O)CH2CH2-Si(111) Functionality to Control Interfacial Chemical and Electronic Properties During the Atomic-Layer Deposition of Ultrathin Oxides on Si(111). AB - Silicon surfaces terminated with a mixed monolayer containing both a propyl aldehyde functionality and methyl groups were prepared and used to control the interfacial chemical and electronic properties of Si(111) surfaces during atomic layer deposition (ALD) of Al2O3 or MnO. Si(111) surfaces functionalized only with the aldehyde moiety exhibited surface recombination velocities, S, of 2500 +/- 600 cm s(-1) whereas the mixed CH3-/HC(O)CH2CH2-Si(111) surfaces displayed S = 25 +/- 7 cm s(-1). During the ALD growth of either Al2O3 or MnO, both the HC(O)CH2CH2-Si(111) and CH3-/HC(O)CH2CH2-Si(111) surfaces produced increased metal oxide deposition at low cycle number, relative to H-Si(111) or CH3-Si(111) surfaces. As detected by X-ray photoelectron spectroscopy after the ALD process, the CH3- and mixed CH3-/HC(O)CH2CH2- functionalized Si(111) surfaces exhibited less interfacial SiOx than was observed for ALD of metal oxides on H-Si(111) substrates. PMID- 26262494 TI - Amide I Vibrational Properties Affected by Hydrogen Bonding Out-of-Plane of the Peptide Group. AB - The amide I vibrational properties of a peptide-water complex in various intermolecular configurations are analyzed theoretically to see whether a water molecule with a weak out-of-plane hydrogen bond really induces a large low frequency shift. It is shown that the frequency shift strongly depends on the C?O...H angle, with a larger low-frequency shift as the C?O...H becomes more bent, suggesting that the so-called hydrated helix with a rather low amide I frequency has an additional water molecule located out-of-plane of the peptide group as compared with a typical alpha-helix. The infrared intensity also depends on the angular position of water. A new model parameter set (that can be combined with molecular dynamics) is developed for a more correct representation of the hydration-induced frequency shift. The question regarding the scalar and vectorial nature of the molecular properties related to the frequency shift is also discussed. PMID- 26262495 TI - Enantiomeric Conformation Controls Rate and Yield of Photoinduced Electron Transfer in DNA Sensitized by Ru(II) Dipyridophenazine Complexes. AB - Photosensitized oxidation of guanine is an important route to DNA damage. Ruthenium polypyridyls are very useful photosensitizers, as their reactivity and DNA-binding properties are readily tunable. Here we show a strong difference in the reactivity of the two enantiomers of [Ru(TAP)2(dppz)](2+), by using time resolved visible and IR spectroscopy. This reveals that the photosensitized one electron oxidation of guanine in three oligonucleotide sequences proceeds with similar rates and yields for bound Delta-[Ru(TAP)2(dppz)](2+), whereas those for the Lambda enantiomer are very sensitive to base sequence. It is proposed that these differences are due to preferences of each enantiomer for different binding sites in the duplex. PMID- 26262496 TI - Water Dispersible, Positively and Negatively Charged MoS2 Nanosheets: Surface Chemistry and the Role of Surfactant Binding. AB - Stable aqueous dispersions of atomically thin layered MoS2 nanosheets have been obtained by sonication in the presence of ionic surfactants. The dispersions are stabilized by electrostatic repulsion between the sheets, and we show that the sign of the charge on the MoS2 nanosheets, either positive or negative, can be can be controlled by the choice of the surfactant. Using techniques from solution NMR, we show that the surfactant chains are weakly bound to the MoS2 sheets and undergo rapid exchange with free surfactant chains present in the dispersion. In situ nuclear Overhauser effect spectroscopic measurements provide direct evidence that the surfactant chains lie flat, arranged randomly on the basal plane of the MoS2 nanosheets with their charged headgroup exposed. These results provide a chemical perspective for understanding the stability of these inorganic nanosheets in aqueous dispersions and the origin of the charge on the sheets. PMID- 26262497 TI - Influences of Surface and Ionic Properties on Electricity Generation of an Active Transducer Driven by Water Motion. AB - In this Letter, we discuss the surface, ionic properties, and scale-up potential of an active transducer that generated electricity from natural water motion. When a liquid contacts a solid surface, an electrical double layer (EDL) is always formed at the solid/liquid interface. By modulating the EDL, the active transducer could generate a peak voltage of ~3 V and a peak power of ~5 MUW. Interestingly, there were specific salinities of solution droplets that showed maximum performance and different characteristics according to the ions' nature. Analyzing the results macroscopically, we tried to figure out the origins of the active transducing precipitated by ions dynamics. Also, we demonstrated the scale up potential for practical usage by multiple electrode design. PMID- 26262498 TI - Channeling Vibrational Energy To Probe the Electronic Density of States in Metal Clusters. AB - We investigate the electronic density of states (DOS) of isolated neutral cobalt clusters by probing the temperature-modulated population of electronic states through UV photoionization. The temperature is controlled via resonant excitation of lattice vibrations using the free-electron laser FELICE, after which the vibrational and electronic systems equilibrate through the electron-phonon coupling, redistributing the population of electronic states. The data are analyzed by surface photoemission theory, modified to incorporate the realistic DOS. PMID- 26262499 TI - Experimental and Theoretical Investigations of Magnetic Exchange Pathways in Structurally Diverse Iron(III) Schiff-Base Complexes. AB - The synthesis, and the structural and magnetic properties, of the following new iron(III) Schiff base complexes with the {O',N,O"}-chelating ligand H2L (2 hydroxyphenylsalicylaldimine) are reported: K[FeL2].H2O (1), (Pr3NH)[FeL2].2CH3OH (2), [FeL(bpyO2) (CH3OH)][FeL2].CH3OH (3), [Fe2L3(CH3OH)].2CH3OH.H2O (4), and [{Fe2L2}(MU-OH)2{FeL(bpyO2)}2][BPh4]2.2H2O (5), where Pr3NH(+) represents the tripropylammonium cation and bpyO2 stands for 2,2'-bipyridine-N-dioxide. A thorough density functional theory (DFT) study of magnetic interactions (the isotropic exchange) at the B3LYP/def-TZVP level of theory was employed, and calculations have revealed superexchange pathways through intramolecular/intermolecular noncovalent contacts (pi-pi stacking, C-H...O and O H...O hydrogen bonds, diamagnetic metal cations) and/or covalent bonds ((MU O(Ph), MU-OH) or bis(MU-O(Ph)) bridging modes), which helped us to postulate trustworthy spin Hamiltonians for magnetic analysis of experimental data. Within the reported family of compounds 1-5, the mediators of the antiferromagnetic exchange can be sorted by their increasing strength as follows: pi-pi stacking (J(DFT) = -0.022 cm(-1)/J(mag) = -0.025(4) cm(-1) in 2) < C-H...O contacts and pi pi stacking (J(DFT) = -0.19 cm(-1)/J(mag) = -0.347(9)cm(-1) in 1) < O-H...O hydrogen bonds (J(DFT) = -0.53 cm(-1)/J(mag) = -0.41(1) cm(-1) in 3) < bis(MU O(Ph)) bridge (J(DFT) = -13.8 cm(-1)/J(mag) = -12.3(9) cm(-1) in 4) < (MU-O(Ph), MU-OH) bridge (J(DFT) = -18.0 cm(-1)/J(mag) = -17.1(2) cm(-1) in 5), where J(DFT) and J(mag) are the isotropic exchange parameters derived from DFT calculations, and analysis of the experimental magnetic data, respectively. The good agreement between theoretically calculated and experimentally derived isotropic exchange parameters suggests that this procedure is applicable also for other chemical and structural systems to interpret magnetic data properly. PMID- 26262500 TI - Influencing Anesthesia Provider Behavior Using Anesthesia Information Management System Data for Near Real-Time Alerts and Post Hoc Reports. AB - In this review article, we address issues related to using data from anesthesia information management systems (AIMS) to deliver near real-time alerts via AIMS workstation popups and/or alphanumeric pagers and post hoc reports via e-mail. We focus on reports and alerts for influencing the behavior of anesthesia providers (i.e., anesthesiologists, anesthesia residents, and nurse anesthetists). Multiple studies have shown that anesthesia clinical decision support (CDS) improves adherence to protocols and increases financial performance through facilitation of billing, regulatory, and compliance documentation; however, improved clinical outcomes have not been demonstrated. We inform developers and users of feedback systems about the multitude of concerns to consider during development and implementation of CDS to increase its effectiveness and to mitigate its potentially disruptive aspects. We discuss the timing and modalities used to deliver messages, implications of outlier-only versus individualized feedback, the need to consider possible unintended consequences of such feedback, regulations, sustainability, and portability among systems. We discuss statistical issues related to the appropriate evaluation of CDS efficacy. We provide a systematic review of the published literature (indexed in PubMed) of anesthesia CDS and offer 2 case studies of CDS interventions using AIMS data from our own institution illustrating the salient points. Because of the considerable expense and complexity of maintaining near real-time CDS systems, as compared with providing individual reports via e-mail after the fact, we suggest that if the same goal can be accomplished via delayed reporting versus immediate feedback, the former approach is preferable. Nevertheless, some processes require near real-time alerts to produce the desired improvement. Post hoc e-mail reporting from enterprise-wide electronic health record systems is straightforward and can be accomplished using system-independent pathways (e.g., via built-in e-mail support provided by the relational database management system). However, for some of these enterprise-wide systems, near real-time data access, necessary for CDS that generates concurrent alerts, has been challenging to implement. PMID- 26262501 TI - Deleterious Impact of Donor-Specific Anti-HLA Antibodies Toward HLA-Cw and HLA-DP in Kidney Transplantation. AB - BACKGROUND: It is widely accepted that HLA donor-specific antibodies (DSA) are associated with antibody-mediated rejection and graft loss. However, in many transplant programs, preformed anti-HLA-Cw and anti-HLA-DP DSA are not considered in organ allocation policies because their clinical relevance is still uncertain. METHODS: We analyzed the clinical impact of Cw/DP DSA through a retrospective study, comparing 48 patients transplanted with isolated preformed Cw/DP DSA (Cw/DP DSA group) with (i) 104 matched HLA-sensitized kidney transplant recipients with No DSA at D0 (No DSA group) and (ii) 47 kidney transplant recipients with preformed A, -B, -DR, -DQ DSA (A/B/DR/DQ DSA group). RESULTS: A positive flow cytometry crossmatch in the Cw/DP DSA group was more frequent than in the No DSA group and as frequent as in the A/B/DR/DQDSA group. Two years after transplantation, the biopsy-proven acute rejection-free survival was worse in the Cw/DP and A/B/DR/DQ DSA groups than in the No DSA group (65%, 84%, 93%, P = 0.001 and P = 0.05, respectively). Accordingly, graft survival was lower in the Cw/DP and the A/B/DR/DQ DSA groups than in the No DSA group (87%, 89%, 95%, P = 0.02 and P = 0.1, respectively). CONCLUSIONS: These results suggest that preformed anti-HLA-Cw and anti-HLA-DP DSA are as deleterious as anti-HLA A/B/DR/DQ DSA. It justifies their inclusion in kidney allocation programs and in immunological risk stratification algorithms. PMID- 26262502 TI - Using Genetic Variation to Predict and Extend Long-term Kidney Transplant Function. AB - Renal transplantation has transformed the life of patients with end-stage renal disease and other chronic kidney disorders by returning endogenous kidney function and enabling patients to cease dialysis. Several clinical indicators of graft outcome and long-term function have been established. Although rising creatinine levels and graft biopsy can be used to determine graft loss, identifying early predictors of graft function will not only improve our ability to predict long-term graft outcome but importantly provide a window of opportunity to therapeutically intervene to preserve graft function before graft failure has occurred. Since understanding the importance of matching genetic variation at the HLA region between donors and recipients and translating this into clinical practise to improve transplant outcome, much focus has been placed on trying to identify additional genetic predictors of transplant outcome/function. This review will focus on how candidate gene studies have identified variants within immunosuppression, immune response, fibrotic pathways, and specific ethnic groups, which correlate with graft outcome. We will also discuss the challenges faced by candidate gene studies, such as differences in donor and recipient selection criteria and use of small data sets, which have led to many genes failing to be consistently associated with transplant outcome. This review will also look at how recent advances in our understanding of and ability to screen the genome are starting to provide new insights into the mechanisms behind long-term graft loss and with it the opportunity to target these pathways therapeutically to ultimately increase graft lifespan and the associated benefits to patients. PMID- 26262503 TI - Oral Platelet-Derived Growth Factor and Vascular Endothelial Growth Factor Inhibitor Sunitinib Prevents Chronic Allograft Injury in Experimental Kidney Transplantation Model. AB - BACKGROUND: Expression of both platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) is increased during the development of chronic rejection which remains the major reason for late allograft loss in clinical kidney transplantation. Sunitinib is a tyrosine kinase inhibitor which inhibits both VEGF and PDGF receptors. Here we investigated its effect on the development of chronic rejection. METHODS: Rat aortic denudation model was used to define sunitinib dose. In vitro studies were done to investigate the effect of sunitinib on smooth muscle cell proliferation and migration. Kidney transplantations were performed from dark agouti rat strain (DA) to Wistar furth rat strain rats and syngenic DA-DA grafts were used as controls. Allografts were immunosuppressed either with cyclosporine or with cyclosporine and sunitinib. Grafts were harvested at 5 and 90 days for histology and immunohistochemistry. Serum creatinine levels were measured weekly to monitor graft function. RESULTS: Sunitinib decreased neointimal formation and smooth muscle cell proliferation and migration in a dose-dependent manner. Sunitinib was well tolerated and almost completely prevented chronic rejection changes and preserved significantly better renal graft function after transplantation. Sunitinib also inhibited chronic PDGF A and -B and VEGF-A and -B expressions. CONCLUSIONS: These results demonstrate that combined inhibition of PGDF and VEGF with sunitinib prevents chronic rejection changes in experimental kidney transplantation which indicates that sunitinib could be a potential intervention also in clinical kidney transplantation. PMID- 26262504 TI - Ex Vivo Perfusion With Adenosine A2A Receptor Agonist Enhances Rehabilitation of Murine Donor Lungs After Circulatory Death. AB - BACKGROUND: Ex vivo lung perfusion (EVLP) enables assessment and rehabilitation of marginal donor lungs before transplantation. We previously demonstrated that adenosine A2A receptor (A2AR) agonism attenuates lung ischemia-reperfusion injury. The current study utilizes a novel murine EVLP model to test the hypothesis that A2AR agonist enhances EVLP-mediated rehabilitation of donation after circulatory death (DCD) lungs. METHODS: Mice underwent euthanasia and 60 minutes warm ischemia, and lungs were flushed with Perfadex and underwent cold static preservation (CSP, 60 minutes). Three groups were studied: no EVLP (CSP), EVLP with Steen solution for 60 minutes (EVLP), and EVLP with Steen solution supplemented with ATL1223, a selective A2AR agonist (EVLP + ATL1223). Lung function, wet/dry weight, cytokines and neutrophil numbers were measured. Microarrays were performed using the Affymetrix GeneChip Mouse Genome 430A 2.0 Array. RESULTS: Ex vivo lung perfusion significantly improved lung function versus CSP, which was further, significantly improved by EVLP + ATL1223. Lung edema, cytokines, and neutrophil counts were reduced after EVLP and further, significantly reduced after EVLP + ATL1223. Gene array analysis revealed differential expression of 1594 genes after EVLP, which comprise canonical pathways involved in inflammation and innate immunity including IL-1, IL-8, IL-6, and IL-17 signaling. Several pathways were uniquely regulated by EVLP + ATL1223 including the downregulation of genes involved in IL-1 signaling, such as ADCY9, ECSIT, IRAK1, MAPK12, and TOLLIP. CONCLUSIONS: Ex vivo lung perfusion modulates proinflammatory genes and reduces pulmonary dysfunction, edema, and inflammation in DCD lungs, which are further reduced by A2AR agonism. This murine EVLP model provides a novel platform to study rehabilitative mechanisms of DCD lungs. PMID- 26262505 TI - Logistical Factors Influencing Cold Ischemia Times in Deceased Donor Kidney Transplants. AB - BACKGROUND: Prolonged cold ischemia time (CIT) is associated with a significant risk of short- and long-term graft failure in deceased donor kidney transplants across the world. The aim of this prospective longitudinal study was to determine the importance of logistical factors on CIT. METHOD: Data on 1763 transplants were collected prospectively over 14 months from personnel in 16 transplant centers, 19 histocompatibility and immunogenetics laboratories, transport providers, and National Health Service Blood and Transplant. RESULTS: The overall mean CIT was 13.8 hours, with significant center variation (P < 0.0001). Factors that significantly reduced CIT were donation after circulatory death (P = 0.03), shorter transport time (P = 0.0002), use of virtual crossmatch (XM) (P < 0.0001), and use of donor blood for pretransplant XM (P < 0.0001). The CIT for transplants that went ahead with a virtual XM was 3 hours shorter than those requiring a pretransplant XM (P < 0.0001). There was a mean delay of 3 hours in starting transplants despite organ, recipient, and pretransplant XM result being ready, suggesting that theater access contributes significantly to increased CIT. DISCUSSION: This study identifies logistical factors relating to donor, transport, crossmatching, recipient, and theater that impact significantly on CIT in deceased donor renal transplantation, some of which are modifiable; attention should be focussed on addressing all of these. PMID- 26262506 TI - Live Donor Renal Transplant With Simultaneous Bilateral Nephrectomy for Autosomal Dominant Polycystic Kidney Disease Is Feasible and Satisfactory at Long-term Follow-up. AB - BACKGROUND: Timing of bilateral nephrectomy (BN) is controversial in patients with refractory symptoms of autosomal dominant polycystic kidney disease (APKD) in need of a renal transplant. METHODS: Adults who underwent live donor renal transplant (LRT) + simultaneous BN (SBN) from August 2003 to 2013 at a single transplant center (n = 66) were retrospectively compared to a matched group of APKD patients who underwent LRT alone (n = 52). All patients received general health and polycystic kidney symptom surveys. RESULTS: Simultaneous BN increased operative duration, estimated blood loss, transfusions, intravenous fluid, and hospital length of stay. Most common indications for BN were pain, loss of abdominal domain, and early satiety. There were more intraoperative complications for LRT + SBN (6 vs 0, P = 0.03; 2 vascular, 2 splenic, and 1 liver injury; 1 reexploration to adjust graft positioning). There were no differences in Clavien Dindo grade I or II (39% vs 25%, P = 0.12) or grade III or IV (7.5% vs 5.7%, P = 1.0) complications during the hospital course. There were no surgery-related mortalities. There were no differences in readmission rates (68% vs 48%, P = 0.19) or readmissions requiring procedures (25% vs. 20%, P = 0.51) over 12 months. One hundred percent of LRT + SBN allografts functioned at longer than 1 year for those available for follow-up. Survey response rate was 40% for LRT alone and 56% for LRT + SBN. One hundred percent of LRT + SBN survey responders were satisfied with their choice of having BN done simultaneously. CONCLUSIONS: Excellent outcomes for graft survival, satisfaction, and morbidity suggest that the combined operative approach be preferred for patients with symptomatic APKD to avoid multiple procedures, dialysis, and costs of staged operations. PMID- 26262507 TI - Support of Neuronal Growth Over Glial Growth and Guidance of Optic Nerve Axons by Vertical Nanowire Arrays. AB - Neural cultures are very useful in neuroscience, providing simpler and better controlled systems than the in vivo situation. Neural tissue contains two main cell types, neurons and glia, and interactions between these are essential for appropriate neuronal development. In neural cultures, glial cells tend to overgrow neurons, limiting the access to neuronal interrogation. There is therefore a pressing need for improved systems that enable a good separation when coculturing neurons and glial cells simultaneously, allowing one to address the neurons unequivocally. Here, we used substrates consisting of dense arrays of vertical nanowires intercalated by flat regions to separate retinal neurons and glial cells in distinct, but neighboring, compartments. We also generated a nanowire patterning capable of guiding optic nerve axons. The results will facilitate the design of surfaces aimed at studying and controlling neuronal networks. PMID- 26262508 TI - Group 4 metal complexes of Trost's semi-crown ligand: synthesis, structural characterization and studies on the ring-opening polymerization of lactides and epsilon-caprolactone. AB - The synthesis of titanium(IV), zirconium(IV) and hafnium(IV) complexes of Trost's semi-crown ligand is described. All complexes were fully characterized by 1H and 13C NMR and mass spectroscopy. The molecular structures of the representative complexes 2, 3 and 4 were determined by single-crystal X-ray diffraction studies. The X-ray diffraction studies reveal that complexes 2, 3 and 4 crystallized in an orthorhombic crystal system. Complexes 2 and 3 have a monomeric structure in the solid state with distorted octahedral geometry around the metal center, whereas complex 4 was found to crystallize in a trimeric structure bridging with an oxygen atom, where the geometry around the titanium is distorted trigonal bipyramidal. The activities and stereoselectivities of these complexes toward the ring-opening polymerization (ROP) of lactides (L-LA and rac-LA) and epsilon caprolactone (CL) have been investigated. Complexes 1-4 were found to be efficient single-component initiators for the ring-opening polymerization of cyclic esters and yielded high molecular weight polymers (Mn) with narrow molecular weight distributions (MWD).The microstructure of the resultant polylactides (PLAs) from rac-LA was determined. Complexes 2 and 3 afforded isotactic-enriched PLA (Pm = 0.78-0.71) with narrow MWD (1.07-1.04), on the other hand complexes 1 and 4 produced atactic PLA. Kinetic and post polymerization studies confirm that the polymerization proceeds through the coordination insertion mechanism. PMID- 26262509 TI - Triboelectric Nanogenerators as a Self-Powered 3D Acceleration Sensor. AB - A novel self-powered acceleration sensor based on triboelectric nanogenerator is proposed, which consists of an outer transparent shell and an inner mass-spring damper mechanical system. The PTFE films on the mass surfaces can slide between two aluminum electrodes on an inner wall owing to the acceleration in the axis direction. On the basis of the coupling of triboelectric and electrostatic effects, the potential difference between the two aluminum electrodes is generated in proportion to the mass displacement, which can be used to characterize the acceleration in the axis direction with a detection range from about 13.0 to 40.0 m/s(2) at a sensitivity of 0.289 V.s(2)/m. With the integration of acceleration sensors in three axes, a self-powered 3D acceleration sensor is developed for vector acceleration measurement in any direction. The self-powered 3D acceleration sensor has excellent performance in the stability test, and the output voltages have a little decrease of ~6% after 4000 cycles. Moreover, the self-powered acceleration sensor can be used to measure high collision acceleration, which has potential practicability in automobile security systems. PMID- 26262510 TI - Pheochromocytomas and Paragangliomas: An Update on Recent Molecular Genetic Advances and Criteria for Malignancy. AB - Pheochromocytomas are uncommon neuroendocrine tumors arising in the adrenal medulla, whereas paragangliomas arise from chromaffin cells in sympathetic and parasympathetic locations outside of the adrenal gland. Molecular genetic studies in the past few years have identified >10 genes involved in the pathogenesis of pheochromocytomas and paragangliomas, including RET oncogene, involved in the pathogenesis of multiple endocrine neoplasia (MEN) 2A and 2B, von Hippel-Lindau tumor-suppressor gene, neurofibromatosis type 1 gene, succinate dehydrogenase, THEM127, and several others. The presence of genetic alterations in some of these genes such as in MEN 2A and 2B can be used to diagnose these disorders clinically, and other mutations such as succinate dehydrogenase can be used in the pathologic prediction of benign and malignant pheochromocytomas and paragangliomas. Although it has been difficult to separate benign and malignant pheochromocytomas and paragangliomas, recent studies that may predict the behavior of these chromaffin-derived neoplasms have been reported. The Pheochromocytoma of the Adrenal Scale Score and the Grading system for Adrenal Pheochromocytoma and Paraganglioma scoring system are also discussed. PMID- 26262511 TI - Tumor Heterogeneity in Breast Cancer. AB - Tumor heterogeneity is the topic de jour, partly because molecular biologists and researchers are identifying it using sophisticated gene/DNA analysis techniques. Clinicians and pathologists are well acquainted with marked variability in clinical presentations, tumor histology, and, more importantly, clinical outcomes of their patients. In this review, we address these issues head-on and document that tumor heterogeneity is an old friend (or, more correctly, a foe). We described heterogeneity that exists at all levels-clinical, histologic, and molecular-and briefly outline the strategies that have been used by clinicians and pathologists to tackle this complicated issue. PMID- 26262512 TI - New Guideline for the Reporting of Studies Developing, Validating, or Updating a Multivariable Clinical Prediction Model: The TRIPOD Statement. AB - Prediction models are developed to aid health care providers in estimating the probability that a specific outcome or disease is present (diagnostic prediction models) or will occur in the future (prognostic prediction models), to inform their decision making. Prognostic models here also include models to predict treatment outcomes or responses; in the cancer literature often referred to as predictive models. Clinical prediction models have become abundant. Pathology measurement or results are frequently included as predictors in such prediction models, certainly in the cancer domain. Only when full information on all aspects of a prediction modeling study are clearly reported, risk of bias and potential usefulness of the prediction model can be adequately assessed. Many reviews have illustrated that the quality of reports on the development, validation, and/or adjusting (updating) of prediction models, is very poor. Hence, the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) initiative has developed a comprehensive and user-friendly checklist for the reporting of studies on, both diagnostic and prognostic, prediction models. The TRIPOD Statement intends to improve the transparency and completeness of reporting of studies that report solely on development, both development and validation, and solely on the validation (with or without updating) of diagnostic or prognostic, including predictive, models. PMID- 26262513 TI - Triple-negative Breast Carcinoma: Morphologic and Molecular Subtypes. AB - Breast carcinoma is a heterogenous disease. Carcinomas lacking expression of estrogen, progesterone, and HER2/neu receptors by immunohistochemistry and Her2 amplification are designated as triple negative. This group of carcinomas comprises approximately 10% to 20% of all breast carcinomas and is characterized by an aggressive nature with shorter rates of disease-free and overall survival. This aggressive behavior is further compounded by the lack of available targeted therapies. Patients receive cytoxic chemotherapy regimens. Although tumors are initially sensitive to this therapy, drugs are toxic and ineffective in maintaining long-term response thereby providing limited benefit. Much effort is being spent on this group of cancers for the identification of appropriate molecular targets, an effort that is proving challenging due to the presence of marked heterogeneity, both at the morphologic and molecular levels. An understanding of the advances in this field is crucial for developing targeted therapies and tailored patient management protocols. This report summarizes the pathologic subtypes of breast cancer that are commonly of a triple-negative immunophenotype and recent molecular advances in this field. PMID- 26262514 TI - Update on the Liver Imaging Reporting and Data System: What the Pathologist Needs to Know. AB - Hepatocellular carcinoma (HCC) is frequently diagnosed noninvasively with imaging techniques. Computed tomography and magnetic resonance imaging play critical roles in the detection, diagnosis, and staging of HCC. Standardization in the interpretation and reporting of imaging modalities has not existed until recently. In 2008, the American College of Radiology supported the development of the Liver Imaging Reporting and Data System (LI-RADS) for standardized terminology, interpretation, and reporting of imaging examinations for the diagnosis of HCC inpatients at risk for HCC. This article reviews the basic concepts of LI-RADS, emphasizing aspects that are most relevant to pathologists, including the categories, diagnostic algorithm, major features, and ancillary features for the diagnosis of HCC. The similarities and differences between LI RADS and other major radiology-based diagnostic systems in terms of target population, intended users, categorization of observations, and imaging methods are addressed. Importantly, LI-RADS and other systems are designed to diagnose progressed HCC with high specificity and modest sensitivity. LI-RADS and other systems are not designed to detect early HCC and so have limited sensitivity for such lesions. Moreover, despite continuous advances in imaging technology, imaging detection and characterization of small (<1 cm) nodules remains limited; in addition, colocalization of small nodules and pathology is difficult. For these reasons LI-RADS and most other systems require lesions to be 1 cm or greater for the noninvasive diagnosis of HCC. As LI-RADS evolves, it is critical that stakeholders, including pathologists, provide expert input to help standardize and enhance reporting of radiologic findings. PMID- 26262515 TI - Customizing Laboratory Information Systems: Closing the Functionality Gap. AB - Highly customizable laboratory information systems help to address great variations in laboratory workflows, typical in Pathology. Often, however, built in customization tools are not sufficient to add all of the desired functionality and improve systems interoperability. Emerging technologies and advances in medicine often create a void in functionality that we call a functionality gap. These gaps have distinct characteristics-a persuasive need to change the way a pathology group operates, the general availability of technology to address the missing functionality, the absence of this technology from your laboratory information system, and inability of built-in customization tools to address it. We emphasize the pervasive nature of these gaps, the role of pathology informatics in closing them, and suggest methods on how to achieve that. We found that a large number of the papers in the Journal of Pathology Informatics are concerned with these functionality gaps, and an even larger proportion of electronic posters and abstracts presented at the Pathology Informatics Summit conference each year deal directly with these unmet needs in pathology practice. A rapid, continuous, and sustainable approach to closing these gaps is critical for Pathology to provide the highest quality of care, adopt new technologies, and meet regulatory and financial challenges. The key element of successfully addressing functionality gaps is gap ownership-the ability to control the entire pathology information infrastructure with access to complementary systems and components. In addition, software developers with detailed domain expertise, equipped with right tools and methodology can effectively address these needs as they emerge. PMID- 26262516 TI - Selected Case From the Arkadi M. Rywlin International Pathology Slide Club: Polypoid Endometriosis in the Pouch of Douglas in a Perimenopausal Woman. AB - A 50-year-old female had a hysterectomy and bilateral salpingo-oophorectomy for adenomyosis, uterine leiomyomas, ovarian and cervical endometriosis. Nine months later, organ imaging revealed a 43*74*52 mm, apparently malignant extraperitoneal mass lying between the vagina and rectum. The patient had been receiving a progestogen. Preoperative needle biopsies were interpreted as recurrent endometriosis. The mass was easily excised and sections were interpreted as polypoid endometriosis with a decidual reaction and foci of necrosis. Slides circulated to the club were from the excised specimen. The majority agreed with this diagnosis although a minority favored a Mullerian adenosarcoma. One club member commented that pseudosarcomatous change, including periglandular stromal cuffing and condensation, may occur in patients on hormones, especially tamoxifen. The patient was well with no recurrence 15 months after surgery. PMID- 26262517 TI - Theories and Methods for Context Sensitive Health Informatics. AB - Context is a key issue when designing, implementing, and evaluating health information technology. Advanced and well-designed systems may not achieve desired outcomes because of complex contextual issues, and unintended consequences are often reported in the literature. The conference introduced in this article integrates sociotechnical and human factors based theories and methods for analysis and evaluation of complex health information technologies in diverse environments demanding high context sensitivity. PMID- 26262519 TI - From Research Prototypes to a Marketable eHealth System. AB - This paper presents three distinct challenges to research and development (R&D) of marketable eHealth systems and suggests strategies to mitigate them. The eHealth system in question is designed to improve self-care and collaboration between remotely monitored heart failure patients and clinicians. By way of introspection and reflection on a current and a previous project, the authors propose solutions for mitigating the central challenges. PMID- 26262520 TI - User Preferences for Improving the Estonian National e-Prescription Service. AB - National e-Prescription services are becoming more common in Europe. While enhancing communication between levels of health care, few solutions have demonstrated enhanced quality of care and patient safety benefits. The article presents the results of a project to map the user needs the Estonian national e prescription service. A survey was conducted among primary care physicians (PCPs) to inquire about their needs in the medication management process. The results showed that PCPs lacked a medication management tool to support patient care across different care settings. A mockup for the national service was developed based on the survey results. The medication management tool features a visual presentation of a patient's medication list and includes decision support functions for allergies and potential interactions. This mockup will be used to further investigate the needs of PCPs as well as other care providers in the medication management process. PMID- 26262521 TI - Physician Experiences with Perceived Pressure to Order Diagnostic Imaging Services. AB - The overuse of diagnostic imaging (DI) services, which is estimated to be 30% in Canada, can expose patients to unnecessary radiation, and strain human and financial resources. This study explored the DI ordering practices of physicians in Canada through semi-structured interviews to gain a deeper understanding of the factors contributing to the overuse of DI services. The majority of participants (n=11; 91%) described feeling pressured by patients to order DI services in circumstances that were unwarranted. The results are followed by a discussion about ways technology (such as a decision support system) could aid in facilitating a dialogue between physicians and patients about when and when not to order DI. PMID- 26262522 TI - The Consumer Health Information System Adoption Model. AB - Derived from overlapping concepts in consumer health, a consumer health information system refers to any of the broad range of applications, tools, and educational resources developed to empower consumers with knowledge, techniques, and strategies, to manage their own health. As consumer health information systems become increasingly popular, it is important to explore the factors that impact their adoption and success. Accumulating evidence indicates a relationship between usability and consumers' eHealth Literacy skills and the demands consumer HISs place on their skills. Here, we present a new model called the Consumer Health Information System Adoption Model, which depicts both consumer eHealth literacy skills and system demands on eHealth literacy as moderators with the potential to affect the strength of relationship between usefulness and usability (predictors of usage) and adoption, value, and successful use (actual usage outcomes). Strategies for aligning these two moderating factors are described. PMID- 26262523 TI - Communication Pattern Regarding Alarms and Patient Signals Between Nurses, Other Health Care Actors, Patients and Devices. AB - CallMeSmart is a context aware communication system for hospitals. The system is being used by nurses and the physicians at the Oncology department, University Hospital of North Norway. CallMeSmart has been designed to increase the efficiency of communication between the nurse-physician and physician-physician. In this study, we have looked at the communication pathways between nurse-nurse and patient-nurse: how nurses define a preference of calling somebody, how alarms and tasks are prioritized, and how this could be implemented into the CallMeSmart system to improve the system for the nurses. This paper discusses how the communication pathways of the patient alarm system can be improved for health care actors in hospitals by revealing the communication patterns according to an alarm between those actors. We address the communication pattern between nurses, other health care actors, patients and the devices used, and discuss possible improvements of this communication. PMID- 26262524 TI - Teaching Nursing Informatics in Australia, Canada and Denmark. AB - Whilst there is a strong interest in nursing informatics in the graduate nurse population, nursing informatics has been slow to be incorporated into the undergraduate nursing curriculum. Nursing schools in Australia, Canada, and Denmark are all currently involved in redeveloping their curricula to include nursing informatics in a meaningful way. This paper provides a brief historical description of the uptake of nursing informatics in each of the three countries and discusses the required future directions and strategies towards incorporating nursing informatics into the undergraduate curriculum. PMID- 26262525 TI - Nurse Practitioner Perceptions of the Impact of Electronic Medical Records Upon Clinical Practice. AB - A survey was conducted in the province of British Columba, Canada with nurse practitioners (NP). This paper reports on the quantitative and qualitative findings of the survey questions specifically focused on NP perceptions of the clinical impacts associated with using electronic medical records (EMRs) in a primary care setting. Findings suggest that although NPs perceived EMRs to improve the overall quality of clinical decisions, challenges remain in terms of tailoring the design of EMRs to address NP needs. PMID- 26262527 TI - Towards Evidence Based Usability in Health Informatics? AB - In a Health Information Technology (HIT) regulatory context in which the usability of this technology is more and more a critical issue, there is an increasing need for evidence based usability practice. However, a clear definition of evidence based usability practice and how to achieve it is still lacking. This paper underlines the need for evidence based HIT design and provides a definition of evidence based usability practice as the conscientious, explicit and judicious use of current best evidence in making decisions in design of interactive systems in health by applying usability engineering and usability design principles that have proven their value in practice. Current issues that hamper evidence based usability practice are highlighted and steps needed to achieve evidence are presented. PMID- 26262528 TI - Usability Evaluation of a Medication Reconciliation and Allergy Review (MRAR) Kiosk: A Methodological Approach for Analyzing User Interactions. AB - Internationally, major efforts are underway to improve medication safety and reduce medication errors during transitions of care. One strategy that has emerged to improve data accuracy and close information gaps is the introduction of software applications and workflow models that allow patients to review, enter, and modify their own patient data (e.g. information about medications they are taking). Evaluating the quality and effectiveness of such patient-facing healthcare applications is critical, especially when this approach is applied to high-stakes clinical tasks such as medication reconciliation. In this paper we describe an approach that has been used to assess the usability of a patient facing medication reconciliation and allergy review (MRAR) kiosk. The phases involved are described along with implications and challenges of carrying out this work. PMID- 26262529 TI - Development of a Video Coding Scheme for Analyzing the Usability and Usefulness of Health Information Systems. AB - Usability has been identified as a key issue in health informatics. Worldwide numerous projects have been carried out in an attempt to increase and optimize health system usability. Usability testing, involving observing end users interacting with systems, has been widely applied and numerous publications have appeared describing such studies. However, to date, fewer works have been published describing methodological approaches to analyzing the rich data stream that results from usability testing. This includes analysis of video, audio and screen recordings. In this paper we describe our work in the development and application of a coding scheme for analyzing the usability of health information systems. The phases involved in such analyses are described. PMID- 26262530 TI - Enhancing Healthcare Provider Feedback and Personal Health Literacy: Dual Use of a Decision Quality Measure. AB - In this protocol for a pilot study we seek to establish the feasibility of using a web-based survey to simultaneously supply healthcare organisations and agencies with feedback on a key aspect of the care experience they provide and increase the generic health decision literacy of the individuals responding. The focus is on the person's involvement in decision making, an aspect of care which is seriously under-represented in current surveys if one adopts the perspective of person-centred care. By engaging with an instrument to assess decision quality the person can, in the one action, provide a retrospective evaluation of a past decision making experience in a specific provider context and enhance their competency in future decision making in any setting. We see this as an exercise in context-sensitive educational health informatics. PMID- 26262531 TI - Medication Review: Human Factors Study Aiming at Helping an Acute Geriatric Unit to Sustain and Systematize the Process. AB - BACKGROUND: Medication Review (MRev) has been implemented in many hospitals to improve patient safety and well-being. However, it seems sometimes difficult to implement, maintain and systematize this process, especially when key-elements are absent. This study focuses on the analysis of a MRev process implemented in an Acute Geriatric Unit (AGU) which, at the time of the study, had no Computerized Physician Order Entry (CPOE) and no sufficient staff to - normally - support the process. OBJECTIVE: This study describes the MRev process as existing in the AGU with a particular focus on the preparatory MRev meeting phase and presents our recommendations to maintain and optimize it. METHODS: Human Factor experts have collected and analyzed data during MRev process by interviews, shadowing observations and video recording from April to October 2014 at Lille University Hospital. RESULTS: MRev process consists of three phases (meeting preparation, MRev meeting and patient discharge) and includes seven main tasks for which actors, documented supports, outcomes and difficulties are identified. Although allocating a fulltime pharmacist for the AGU would solve several problems, the main realistic recommendations concern training for junior and senior actors according to their roles and the improvement of some tasks processes. CONCLUSION: Despite less than optimal conditions as compared to those recommended by the literature, the observed AGU performs an efficient review based on well designed tools and processes. PMID- 26262532 TI - Safer Design - Composable EHRs and Mechanisms for Safety. AB - As the deployment of health information technology progresses, issues of usability and safety, including the possibility of technology-induced errors have come to the fore. Increased complexity of care delivery models and emergent conditions such as the Ebola scare in the US point to the difficulty of design that allows for human cognitive limits while meeting complex needs. We previously described a modular composable approach to health information systems, which gives the end-user some control of design and allows for creation of systems meeting myriad and varied needs. Here we discuss how the different drag/drop interaction paradigm has implications for health IT safety via several mechanisms. These include display fragmentation and the need to changeably prioritize information elements, interruptions, fit to tasks and contexts, and rapid changeability allowing low-cost readjustments when lack of fit is found. PMID- 26262533 TI - Enhancing Patient Safety Event Reporting by K-nearest Neighbor Classifier. AB - Data quality was placed as a major reason for the low utility of patient safety event reporting systems. A pressing need in improving data quality has advanced recent research focus in data entry associated with human factors. The debate on structured data entry or unstructured data entry reveals not only a trade-off problem among data accuracy, completeness, and timeliness, but also a technical gap on text mining. The present study suggested a text classification method, k nearest neighbor (KNN), for predicting subject categories as in our proposed reporting system. Our results demonstrated the feasibility of KNN classifier used for text classification and indicated the advantage of such an application to raise data quality and clinical decision support in reporting patient safety events. PMID- 26262534 TI - Integrating Methods to Evaluate Health Information Systems. AB - There are different methods to evaluate Health Information Systems (HIS), such as Quality Evaluation of software products, human factors, and socio-technical approaches. This work aims to identify the main aspects used to evaluate HIS, and whether there are relationships between issues considered in assessment of software quality and the ones applied specific to the health domain. This was an exploratory study that included a literature search related to HIS evaluation and software quality analyses applying the norms of the International Organization for Standardization (ISO/IEC), to identify aspects and features applied during the assessment process. The result is a proposal of an evaluation method based on the integration of these two evaluative approaches, combining or complementing the considered aspects. The method was applied to an evaluation of a natural language processing system to identify continuity of care in discharge summaries. PMID- 26262536 TI - Information Issues and Contexts that Impair Team Based Communication Workflow: A Palliative Sedation Case Study. AB - Implementing team based workflows can be complex because of the scope of providers involved and the extent of information exchange and communication that needs to occur. While a workflow may represent the ideal structure of communication that needs to occur, information issues and contextual factors may impact how the workflow is implemented in practice. Understanding these issues will help us better design systems to support team based workflows. In this paper we use a case study of palliative sedation therapy (PST) to model a PST workflow and then use it to identify purposes of communication, information issues and contextual factors that impact them. We then suggest how our findings could inform health information technology (HIT) design to support team based communication workflows. PMID- 26262537 TI - The Role of Medical Transcriptionists in Producing High-Quality Documentation. AB - This study aimed to investigate the quality-assurance work conducted by medical transcriptionists in the production of medical records, and the implications of these findings when designing a structured electronic patient record (EPR) system in which physicians are supposed to write documentation themselves. Both qualitative and quantitative methods were applied. Qualitative data were collected through informal discussions and focus-group interviews. Quantitative data were collected through the medical transcriptionists' daily recordings of their quality-assurance work. The results show the many essential quality assurance tasks conducted by medical transcriptionists and the extent of this work. Each medical transcriptionist performs an average of more than six corrections per day, and approximately one of three dictations are corrected. We suggest that these correction and quality-assurance tasks need to be compensated for when designing and developing new structured EPRs. Some quality-assurance tasks may also advantageously be performed by secretaries in the future. PMID- 26262538 TI - A Sequential Data Analysis Approach to Electronic Health Record Workflow. AB - Failure to understand clinical workflow across electronic health record (EHR) tasks is a significant contributor to usability problems. In this paper, we employed sequential data analysis methods with the aim of characterizing patterns of 5 clinicians' information-gathering across 66 patients. Two analyses were conducted. The first one characterized the most common sequential patterns as reflected in the screen transitions. The second analysis was designed to mine and quantify the frequency of sequence occurrence. We observed 27 screen-transition patterns that were employed from 2 to 7 times. Documents/Images and Intake/Output screens were viewed for nearly all patients indicating the importance of these information sources. In some cases, they were viewed more than once which may show that users are following inefficient patterns in the information gathering process. New quantitative methods of analysis as applied to interaction data can yield critical insights in robust designs that better support clinical workflow. PMID- 26262539 TI - Unveiling the Mobile Learning Paradox. AB - A mobile learning paradox exists in Australian healthcare settings. Although it is increasingly acknowledged that timely, easy, and convenient access to health information using mobile learning technologies can enhance care and improve patient outcomes, currently there is an inability for nurses to access information at the point of care. Rapid growth in the use of mobile technology has created challenges for learning and teaching in the workplace. Easy access to educational resources via mobile devices challenges traditional strategies of knowledge and skill acquisition. Redesign of learning and teaching in the undergraduate curriculum and the development of policies to support the use of mobile learning at point of care is overdue. This study explored mobile learning opportunities used by clinical supervisors in tertiary and community-based facilities in two Australian States. Individual, organisation and systems level governance were sub-themes of professionalism that emerged as the main theme and impacts on learning and teaching in situ in healthcare environments. It is imperative healthcare work redesign includes learning and teaching that supports professional identity formation of students during work integrated learning. PMID- 26262540 TI - The Role of the IT Department in Organizational Redesign. AB - Focus within eHealth research is often on development and implementation. However, the role of information systems maintenance and management is often neglected. In order for the IT department to accommodate the needs of the hospitals and continuous change of organization and practice there is a need for developing an understanding of the complex relationship between the IT department and clinical practice. In this paper the concept of redesign is used to deepen our understanding of IT related organizational change in healthcare organizations. In the paper I argue that the IT department is a central partner, steward and power in organizational change and learning in hospitals as the IT department serve both as a barrier and a catalyst of change and flexibility in the organization through management of information systems maintenance and redesign. Therefore it is important to consider and secure appropriate forms for stewarding redesign and learning in cooperation between the health care organizations and the IT department. PMID- 26262541 TI - Monitoring the Amount of Practical Use of eHealth on National Level by Use of Log Data: Lessons Learned. AB - This paper set out to define the lessons learned from the process of characterizing the amount of practical use of eHealth on national level by collecting and comparing log data harvested from national logs in the Nordic countries. The health systems of the Nordic countries are quite similar in structure and their eHealth strategies include similar elements, however when confronted with the specific context in the different systems it proved challenging to define a common set of indicators for monitoring the practical use of eHealth. A thorough analysis of context leading to the definitions of the indicators is the basis needed due to the complexity of the data in the national logs. A comprehensive knowledge of the structure that underlines these logs is of utmost importance when striving for collecting comparable data. Although challenging, the process of defining indicators for practical use of eHealth by data harvested trough national logs is not an impossible task, but a task that requires in depth discussions of definitions of indicators as well as a substantial insight into the architecture and content of the national databases. There is need for continuous work on these indicators to ensure their quality and thus make sure that the defined indicators can meaningfully inform eHealth policies. PMID- 26262542 TI - Work System Characteristics Impacting the Performance and Quality of the Discharge Letter Process. AB - Studies on the impact of a Health Information Technology seldom consider socio technical characteristics of the work system in which the technology is implemented. Yet those dimensions may act as hidden variables that could explain the inconsistency of impact studies' results in terms of performance, quality and satisfaction. This paper reports on the identification of those variables in the discharge letter (DL) process. Human Factors experts performed an analysis of the work system of the DL process in 17 medical units. The DL process is composed of three sub-processes running with work system differing according to the distribution of tasks, the technology implemented and the work organization. Hidden variables identified are: verification by the physician, technology's integration, number of editing cycles, physicians' preferences etc. Those variables can be collected automatically or by questionnaire. Statistical analyses will have to be performed to know which variable explain impact indicators. PMID- 26262544 TI - The Question Concerning Narration of Self in Health Informatics. AB - Narration is central, even crucial, when it comes to embracing the whole individual, continuity of care, and responsible (ethical) handling of the technological construction of the self that takes place in health informatics. This paper will deal with the role of narratives in the construction of health informatics platforms and how different voices should have space for speech on these platforms. Theoretically the paper takes an outset in the actant model for narratives by the French-Lithuanian theorist of linguistics and literature A.-J. Greimas and post-phenomenological readings of human-technology interactions. The main assumption is that certain interactions and voices are absent from the construction of health informatics platforms, because regarded as outside the text of computational and medical practice and expertise. This has implications for what concerns meaning and understanding regarding both the actual users (physicians and medical staff) and excluded users (patients and citizens). PMID- 26262545 TI - Understanding the Context of Patient Safety Through The Lenses of Three IMIA Working Groups. AB - Delivering safe patient centered care remains an important yet elusive goal across healthcare systems worldwide. The complexity of healthcare delivery and the unique contexts where it is delivered necessitates patient safety solutions that go beyond individual perspectives. This paper articulates the current state of patient safety research and HIT from the perspective of three International Medical Informatics Association (IMIA) working groups. Each WG will describe patient safety issues within their domain. We then integrate the three WG perspectives into an integrated model to support research, education and policy development for patient safety where HIT is concerned. PMID- 26262546 TI - The Contextualization of Archetypes: Clinical Template Governance. AB - This paper is a status report from a large-scale openEHR-based EPR project from the North Norway Regional Health Authority. It concerns the standardization of a regional ICT portfolio and the ongoing development of a new process oriented EPR systems encouraged by the unfolding of a national repository for openEHR archetypes. Subject of interest; the contextualization of clinical templates is governed over multiple national boundaries which is complex due to the dependency of clinical resources. From the outset of this, we are interested in how local, regional, and national organizers maneuver to standardize while applying OpenEHR technology. PMID- 26262547 TI - Health Informatics Can Avoid Committing Symbolic Violence by Recognizing and Supporting Generic Decision-making Competencies. AB - 'Symbolic violence' is committed, however well-intentionally, by the imposition of particular conceptualizations of what information, in what form and quality, is needed in order to make an 'informed choice' and hence - by questionable segue - a high quality decision. The social and cultural forms of relevant cognitive capital possessed by those who fail, because of their low general literacy, professionally-set knowledge tests of functional health literacy, are being ignored. Failing to recognise and exploit a particular form of functional decision literacy, in fact leads to symbolic violence being experienced by individuals at any and all levels of general literacy. It leads many to adopt the same range of avoidant and other undesirable strategies within healthcare situations observed in those of low basic literacy. The alternative response we propose exploits the alternative generic decision literacy which comes in the form of the ability to access and use the decision-relevant resources provided for many consumer services and products on comparison websites and magazines. The methodology is the simple form of multi-criteria analysis in which the products' ratings on multiple criteria are combined with criterion weights (supplied by the site) to produce scores and 'best buys' and 'good value for money' verdicts. Our alternative approach extends this approach to healthcare options and permits the incorporation of personal criterion weights in furtherance of person-centred care. Health informaticians, especially those in the decision support field, should build on this widespread generic competence. The fact that it is generic, far from implying context insensitivity, can be seen as a necessary basis for achieving context-sensitivity and sensitivisation at the level of the individual person as they experience a lifelong sequence of healthcare decisions. PMID- 26262551 TI - Loading of PNIPAM Based Microgels with CoFe2O4 Nanoparticles and Their Magnetic Response in Bulk and at Surfaces. AB - The present paper addresses the loading of thermoresponsive poly-N isopropylacrylamide (PNIPAM) based microgel particles with magnetic nanoparticles (MNP: CoFe2O4@PAA (PAA = poly(acrylic acid))) and their response to an external magnetic field. The MNP uptake is analyzed by transmission electron microscopy (TEM). Obviously, the charge combination of MNP and microgels plays an important role for the MNP uptake, but it does not explain the whole uptake process. The MNP uptake results in changes of size and electrophoretic mobility, which is investigated by dynamic light scattering (DLS) and a Zetasizer. The microgels loaded with MNP preserve their thermosensitivity, and they show magnetic separability and are considered as magnetic microgels. After adsorption at a surface the magnetic microgels are studied with a scanning force microscope and indentation experiments. The magnetic microgels show an elongation along the magnetic field parallel to the surface while the height of the microgels (perpendicular to the surface and to the magnetic field) is compressed. This result is in good agreement with simulations of volume change of ferrogels in a magnetic field. PMID- 26262553 TI - A Conductive Self-Healing Hybrid Gel Enabled by Metal-Ligand Supramolecule and Nanostructured Conductive Polymer. AB - Self-healing materials emerge as a fascinating class of materials important for various technological applications. However, achieving the synergistic characteristics of high conductivity, room-temperature self-healing ability, and decent mechanical properties still remains a critical challenge. Here we develop for the first time a hybrid gel based on self-assembled supramolecular gel and nanostructured polypyrrole that synergizes the dynamic assembly/disassembly nature of metal-ligand supramolecule and the conductive nanostructure of polypyrrole hydrogel and exhibits features of high conductivity (12 S m(-1)), appealing mechanical and electrical self-healing property without any external stimuli, and enhanced mechanical strength and flexibility. The attractive characteristics of the hybrid gel are further demonstrated by a flexible yet self healable electrical circuit. Our work shows the great potential of self-healing hybrid gel system in flexible electronics and provides a useful strategy to design multifunctional self-healing materials. PMID- 26262554 TI - Metal-Free Reduction of Aromatic and Aliphatic Nitro Compounds to Amines: A HSiCl3-Mediated Reaction of Wide General Applicability. AB - A new, mild, metal-free, HSiCl3-mediated reduction of both aromatic and aliphatic nitro groups to amines that is of wide general applicability, tolerant of many functional groups, and respectful of the stereochemical integrity of stereocenters is reported. PMID- 26262552 TI - Serum Dyslipidemia Is Induced by Internal Exposure to Strontium-90 in Mice, Lipidomic Profiling Using a Data-Independent Liquid Chromatography-Mass Spectrometry Approach. AB - Despite considerable research into the environmental risks and biological effects of exposure to external beam gamma rays, incorporation of radionuclides has largely been understudied. This dosimetry and exposure risk assessment is challenging for first responders in the field during a nuclear or radiological event. Therefore, we have developed a workflow for assessing injury responses in easily obtainable biofluids, such as urine and serum, as the result of exposure to internal emitters cesium-137 ((137)Cs) and strontium-90 ((90)Sr) in mice. Here we report on the results of the untargeted lipidomic profiling of serum from mice exposed to (90)Sr. We also compared these results to those from previously published (137)Cs exposure to determine any differences in cellular responses based on exposure type. The results of this study conclude that there is a gross increase in the serum abundance of triacylglycerides and cholesterol esters, while phostaphatidylcholines and lysophosphatidylcholines displayed decreases in their serum levels postexposure at study days 4, 7, 9, 25, and 30, with corresponding average cumulative skeleton doses ranging from 1.2 +/- 0.1 to 5.2 +/- 0.73 Gy. The results show significant perturbations in serum lipidome as early as 2 days postexposure persisting until the end of the study (day 30). PMID- 26262555 TI - Enforced Layer-by-Layer Stacking of Energetic Salts towards High-Performance Insensitive Energetic Materials. AB - Development of modern high-performance insensitive energetic materials is significant because of the increasing demands for both military and civilian applications. Here we propose a rapid and facile strategy called the "layer hydrogen bonding pairing approach" to organize energetic molecules via layer-by layer stacking, which grants access to tunable energetic materials with targeted properties. Using this strategy, an unusual energetic salt, hydroxylammonium 4 amino-furazan-3-yl-tetrazol-1-olate, with good detonation performances and excellent sensitivities, was designed, synthesized, and fully characterized. In addition, the expected unique layer-by-layer structure with a high crystal packing coefficient was confirmed by single-crystal X-ray crystallography. Calculations indicate that the layer-stacking structure of this material can absorb the mechanical stimuli-induced kinetic energy by converting it to layer sliding, which results in low sensitivity. PMID- 26262556 TI - Electrical and Optical Characterization of MoS2 with Sulfur Vacancy Passivation by Treatment with Alkanethiol Molecules. AB - We investigated the physical properties of molybdenum disulfide (MoS2) atomic crystals with a sulfur vacancy passivation after treatment with alkanethiol molecules including their electrical, Raman, and photoluminescence (PL) characteristics. MoS2, one of the transition metal dichalcogenide materials, is a promising two-dimensional semiconductor material with good physical properties. It is known that sulfur vacancies exist in MoS2, resulting in the n-type behavior of MoS2. The sulfur vacancies on the MoS2 surface tend to form covalent bonds with sulfur-containing groups. In this study, we deposited alkanethiol molecules on MoS2 field effect transistors (FETs) and then characterized the electrical properties of the devices before and after the alkanethiol treatment. We observed that the electrical characteristics of MoS2 FETs dramatically changed after the alkanethiol treatment. We also observed that the Raman and PL spectra of MoS2 films changed after the alkanethiol treatment. These effects are attributed to the thiol (-SH) end groups in alkanethiols bonding at sulfur vacancy sites, thus altering the physical properties of the MoS2. This study will help us better understand the electrical and optical properties of MoS2 and suggest a way of tailoring the properties of MoS2 by passivating a sulfur vacancy with thiol molecules. PMID- 26262557 TI - Principles and Applications of Broadband Impulsive Vibrational Spectroscopy. AB - We present an experimental setup for recording vibrational coherences and thereby Raman spectra of molecules in their ground and excited electronic states over the 50-3000 cm(-1) spectral range using broadband impulsive vibrational spectroscopy. Our approach relies on the combination of a <10 fs excitation pulse with an uncompressed white light continuum probe, which drastically reduces experimental complexity compared to frequency domain based techniques. We discuss the parameters determining vibrational coherence amplitudes, outline how to optimize the experimental setup including approaches aimed at conclusively assigning vibrational coherences to specific electronic states, and provide a clear comparison with existing techniques. To demonstrate the applicability of our spectroscopic approach we conclude with several examples revealing the evolution of vibrational coherence in rhodopsin and beta-carotene. PMID- 26262560 TI - Bone Tissue Engineering with Multilayered Scaffolds-Part II: Combining Vascularization with Bone Formation in Critical-Sized Bone Defect. AB - Our previous in vivo study showed that multilayered scaffolds made of an angiogenic layer embedded between an osteogenic layer and an osteoconductive layer, with layer thickness in the 100-400 MUm range, resulted in through-the thickness vascularization of the construct even in the absence of exogenous endothelial cells. The angiogenic layer was a collagen-fibronectin gel, and the osteogenic layer was made from nanofibrous polycaprolactone while the osteoconductive layer was made either from microporous hydroxyapatite or microfibrous polycaprolactone. In this follow-up study, we implanted these acellular and cellular multilayered constructs in critical-sized rat calvarial defects and evaluated their vascularization and bone formation potential. Vascularization and bone formation at the defect were evaluated and quantified using microcomputed tomography (microCT) followed by perfusion of the animals with the radio opaque contrast agent, MICROFIL. The extent of bony bridging and union within the critical-sized defect was evaluated using a previously established scoring system from the microCT data set. Similarly the new bone formation in the defect was quantified from the microCT data set as previously reported. Histological evaluation at 4 and 12 weeks validated the microCT findings. Our experimental results showed that acellular multilayered scaffolds with microscale-thick nanofibers and porous ceramic discs with angiogenic zone at their interface can regenerate functional vasculature and bone similar to that of cellular constructs in critical-sized calvarial defects. This result suggests that suitably bioengineered acellular multilayered constructs can be an improved and more translational approach in functional in vivo bone regeneration. PMID- 26262558 TI - Role of STAT1 in Chlamydia-Induced Type-1 Interferon Production in Oviduct Epithelial Cells. AB - We previously reported that Chlamydia muridarum-infected murine oviduct epithelial cells (OE cells) secrete interferon beta (IFN-beta) in a mostly TLR3 dependent manner. However, C. muridarum-infected TLR3-deficient OE cells were still able to secrete detectable levels of IFN-beta into the supernatants, suggesting that other signaling pathways contribute to Chlamydia-induced IFN-beta synthesis in these cells. We investigated the role of STAT1 as a possible contributor in the Chlamydia-induced type-1 IFN production in wild-type (WT) and TLR3-deficient OE cells to ascertain its putative role at early- and late-times during Chlamydia infection. Our data show that C. muridarum infection significantly increased STAT1 gene expression and protein activation in WT OE cells; however, TLR3-deficient OE cells showed diminished STAT1 protein activation and gene expression. There was significantly less IFN-beta detected in the supernatants of C. muridarum-infected OE cells derived from mice deficient in STAT1 when compared with WT OE cells, which suggest that STAT1 is required for the optimal synthesis of IFN-beta during infection. Real-time quantitative polymerase chain reaction analyses of signaling components of the type-1 IFN signaling pathway demonstrated equal upregulation in the expression of STAT2 and IRF7 genes in the WT and TLR3-deficient OE cells, but no upregulation in these genes in the STAT1-deficient OE cells. Finally, experiments in which INFAR1 was blocked with neutralizing antibody revealed that IFNAR1-mediated signaling was critical to the Chlamydia-induced upregulation in IFN-alpha gene transcription, but had no role in the Chlamydia-induced upregulation in IFN-beta gene transcription. PMID- 26262561 TI - The attracting power of the gaze of politicians is modulated by the personality and ideological attitude of their voters: a functional magnetic resonance imaging study. AB - Observing someone rapidly moving their eyes induces reflexive shifts of overt and covert attention in the onlooker. Previous studies have shown that this process can be modulated by the onlooker's personality, as well as by the social features of the person depicted in the cued face. Here, we investigated whether an individual's preference for social dominance orientation, in-group perceived similarity (PS), and political affiliation of the cued-face modulated neural activity within specific nodes of the social attention network. During functional magnetic resonance imaging, participants were requested to perform a gaze following task to investigate whether the directional gaze of various Italian political personages might influence the oculomotor behaviour of in-group or out group voters. After scanning, we acquired measures of PS in personality traits with each political personage and preference for social dominance orientation. Behavioural data showed that higher gaze interference for in-group than out-group political personages was predicted by a higher preference for social hierarchy. Higher blood oxygenation level-dependent activity in incongruent vs. congruent conditions was found in areas associated with orienting to socially salient events and monitoring response conflict, namely the left frontal eye field, right supramarginal gyrus, mid-cingulate cortex and left anterior insula. Interestingly, higher ratings of PS with the in-group and less preference for social hierarchy predicted increased activity in the left frontal eye field during distracting gaze movements of in-group as compared with out-group political personages. Our results suggest that neural activity in the social orienting circuit is modulated by higher-order social dimensions, such as in group PS and individual differences in ideological attitudes. PMID- 26262562 TI - London dispersion in molecular chemistry--reconsidering steric effects. AB - London dispersion, which constitutes the attractive part of the famous van der Waals potential, has long been underappreciated in molecular chemistry as an important element of structural stability, and thus affects chemical reactivity and catalysis. This negligence is due to the common notion that dispersion is weak, which is only true for one pair of interacting atoms. For increasingly larger structures, the overall dispersion contribution grows rapidly and can amount to tens of kcal mol(-1) . This Review collects and emphasizes the importance of inter- and intramolecular dispersion for molecules consisting mostly of first row atoms. The synergy of experiment and theory has now reached a stage where dispersion effects can be examined in fine detail. This forces us to reconsider our perception of steric hindrance and stereoelectronic effects. The quantitation of dispersion energy donors will improve our ability to design sophisticated molecular structures and much better catalysts. PMID- 26262563 TI - Genetic control of cuticular wax compounds in Eucalyptus globulus. AB - Plant cuticular wax compounds perform functions that are essential for the survival of terrestrial plants. Despite their importance, the genetic control of these compounds is poorly understood outside of model taxa. Here we investigate the genetic basis of variation in cuticular compounds in Eucalyptus globulus using quantitative genetic and quantitative trait loci (QTL) analyses. Quantitative genetic analysis was conducted using 246 open-pollinated progeny from 13 native sub-races throughout the geographic range. QTL analysis was conducted using 112 clonally replicated progeny from an outcross F2 population. Nine compounds exhibited significant genetic variation among sub-races with three exhibiting signals of diversifying selection. Fifty-two QTL were found with co location of QTL for related compounds commonly observed. Notable among these was the QTL for five wax esters, which co-located with a gene from the KCS family, previously implicated in the biosynthesis of cuticular waxes in Arabidopsis. In combination, the QTL and quantitative genetic analyses suggest the variation and differentiation in cuticular wax compounds within E. globulus has a complex genetic origin. Sub-races exhibited independent latitudinal and longitudinal differentiation in cuticular wax compounds, likely reflecting processes such as historic gene flow and diversifying selection acting upon genes that have diverse functions in distinct biochemical pathways. PMID- 26262564 TI - Central Vein Preservation in Critical Venous Access. AB - Introduction The lack of suitable veins in children with critical central venous access requirements is a major obstacle to optimal care and is potentially life threatening. We present outcomes following the use of vein-preserving (VP) surgical techniques, notably the sheath exchange for tunneled lines (SETL). Materials and Methods A retrospective, single observer analysis of a prospectively maintained departmental logbook as well as the medical records of patients. Two broad groups of central line replacements were identified; those inserted following removal of a previous line and a traditional "plastic-free" (PF) period and those exchanged without such an interval. Results Overall, 19 lines were directly exchanged during the study period and compared with 34 inserted after a PF period. Similar catheter life spans and infection rates were demonstrated in each group; 125 (range, 78-173) days in VP exchanges versus 122 (range, 70-175) days in PF replacements (p = 0.41). Line Sepsis resulting in removal or change of line occurred at 103 (range, 60-147) days in VP group versus 104 (range, 45-164) days in PF (p = 0.73). Conclusion For children with critical venous access requirements, direct line exchange procedures are a robust and reproducible means of vein preservation. The outcomes compare favorably with those following the more traditional removal, a PF period and reinsertion. PMID- 26262565 TI - Qualitative research synthesis: methodological guidance for systematic reviewers utilizing meta-aggregation. AB - Qualitative synthesis informs important aspects of evidence-based healthcare, particularly within the practical decision-making contexts that health professionals work in. Of the qualitative methodologies available for synthesis, meta-aggregation is most transparently aligned with accepted conventions for the conduct of high-quality systematic reviews. Meta-aggregation is philosophically grounded in pragmatism and transcendental phenomenology. The essential characteristics of a meta-aggregative review are that the reviewer avoids re interpretation of included studies, but instead accurately and reliably presents the findings of the included studies as intended by the original authors. This study reports on the methodology and methods of meta-aggregation within the structure of an a priori protocol and standardized frameworks for reporting of results by over-viewing the essential components of a systematic review report. PMID- 26262566 TI - Conducting systematic reviews of association (etiology): The Joanna Briggs Institute's approach. AB - The systematic review of evidence is the research method which underpins the traditional approach to evidence-based healthcare. There is currently no uniform methodology for conducting a systematic review of association (etiology). This study outlines and describes the Joanna Briggs Institute's approach and guidance for synthesizing evidence related to association with a predominant focus on etiology and contributes to the emerging field of systematic review methodologies. It should be noted that questions of association typically address etiological or prognostic issues.The systematic review of studies to answer questions of etiology follows the same basic principles of systematic review of other types of data. An a priori protocol must inform the conduct of the systematic review, comprehensive searching must be performed and critical appraisal of retrieved studies must be carried out.The overarching objective of systematic reviews of etiology is to identify and synthesize the best available evidence on the factors of interest that are associated with a particular disease or outcome. The traditional PICO (population, interventions, comparators and outcomes) format for systematic reviews of effects does not align with questions relating to etiology. A systematic review of etiology should include the following aspects: population, exposure of interest (independent variable) and outcome (dependent variable).Studies of etiology are predominantly explanatory or predictive. The objective of reviews of explanatory or predictive studies is to contribute to, and improve our understanding of, the relationship of health related events or outcomes by examining the association between variables. When interpreting possible associations between variables based on observational study data, caution must be exercised due to the likely presence of confounding variables or moderators that may impact on the results.As with all systematic reviews, there are various approaches to present the results, including a narrative, graphical or tabular summary, or meta-analysis. When meta-analysis is not possible, a set of alternative methods for synthesizing research is available. On the basis of the research question and objectives, narrative, tabular and/or visual approaches can be used for data synthesis. There are some special considerations when conducting meta-analysis for questions related to risk and correlation. These include, but are not limited to, causal inference.Systematic review and meta-analysis of studies related to etiology is an emerging methodology in the field of evidence synthesis. These reviews can provide useful information for healthcare professionals and policymakers on the burden of disease. The standardized Joanna Briggs Institute approach offers a rigorous and transparent method to conduct reviews of etiology. PMID- 26262568 TI - Comparison of Tension-Band Wiring With the Cable Pin System in Patella Fractures: A Randomized Prospective Study. AB - OBJECTIVES: To compare the outcome of tension-band wiring (TBW) with the cable pin system (CPS) for transverse fractures of the patella. DESIGN: Randomized prospective study. SETTING: Academic Level I trauma center. PATIENTS/PARTICIPANTS: From February 2008 to December 2011, 73 consecutive patients with transverse fractures of the patella were prospectively enrolled in this study. INTERVENTION: The patients were randomly divided into 2 groups: one group was treated using the CPS, and the other group was treated using the modified TBW. MAIN OUTCOME MEASUREMENTS: The clinical outcome assessment included analyses of the radiographic images, the modified Hospital for Special Surgery scoring system, and complications. RESULTS: The follow-up time ranged from 12 to 29 months. All fractures healed, with a union rate of 100%. The fracture healing time was significantly shorter in the CPS group (8.51 +/- 2.59 weeks, n = 34) compared with the TBW group (11.79 +/- 3.04 weeks, n = 39). Postoperative complications in the CPS and TBW groups were observed in 1 and 9 patients, respectively, a difference that was statistically significant. The mean Hospital for Special Surgery score for the CPS group (90.53 +/- 5.19 points) was significantly higher than that for the TBW group (81.36 +/- 12.71 points). CONCLUSIONS: The CPS is a viable option for transverse fractures of the patella and is associated with a shorter healing time, fewer complications, and better function than TBW. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. PMID- 26262567 TI - Successful rhIGF1 treatment for over 5 years in a patient with severe insulin resistance due to homozygous insulin receptor mutation. AB - BACKGROUND: Congenital insulin resistance syndromes are caused by biallelic mutations within the insulin receptor gene (INSR). Recombinant human insulin-like growth factor (rhIGF1) has been used with mixed success; however, rigorous assessment of its efficacy is lacking. Here, we describe a child with a homozygous mutation in INSR successfully treated with rhIGF1 for more than 5 years. CASE REPORT: The patient presented with osmotic diabetes symptoms and was noted to have dysplastic dentition, hypertrichosis, coarse and dysmorphic facial features. Acanthosis nigricans, skin tags and rugated hyperkeratosis were also evident on the posterior neck, axilla and groin. A homozygous INSR essential splice site mutation (c.1268 + 2T > C, p.G374 fs*12) was identified, for which both parents were found to be heterozygous. The patient was treated with twice daily injections of rhIGF1 and metformin for more than 5 years with improvement in her acanthosis nigricans, hyperkeratosis and hypertrichosis. A dramatic fall in fasting insulin, HOMA-IR and HbA1c has been maintained over the entire course of treatment without adverse effects. Her linear growth velocity has remained on target for her predicted adult height. DISCUSSION: Our case demonstrates the effectiveness of rhIGF1 as an early treatment in a patient with a biallelic mutation within INSR without evidence of fluid retention, retinopathy, muscle pain, heart failure, cerebral infarcts or benign intracranial hypertension. Her case suggests rhIGF1 can and should be considered as an initial treatment option instead of as a final option in those with INSR mutations. PMID- 26262569 TI - Precontoured plate fixation with interfragmentary lag screw use in a middle third clavicle fracture fixation. AB - Middle third clavicle fractures are common injuries that need surgical fixation in a certain subset of patients. The use of pre-contoured clavicle plates facilitates intra-operative fixation and can reduce soft tissue irritation and hardware removal rates. Lag screw fixation is a well-established technique for the treatment of oblique fractures. Empirical application of this method in clavicle fracture fixation and clavicle non-union treatment has been reported previously. A recent biomechanical study supports the use of a lag screw technique in clavicle fracture fixation when possible. We report a 46 year old patient with a mid-shaft right clavicle fracture who was treated with this technique, which resulted in an excellent clinical outcome. PMID- 26262572 TI - MOF-Derived Porous Co3O4 Hollow Tetrahedra with Excellent Performance as Anode Materials for Lithium-Ion Batteries. AB - Porous Co3O4 hollow tetrahedra were prepared through the thermolysis of metal organic frameworks and presented reversible capacities of 1196 and 1052 mAh g(-1) at 50 and 200 mA g(-1) after 60 charge/discharge cycles, respectively. Such excellent performances stem from the well-defined hollow structure of Co3O4 tetrahedra. PMID- 26262570 TI - Food craving as a mediator between addictive-like eating and problematic eating outcomes. AB - BACKGROUND: There is growing interest and debate about whether an addictive process contributes to problematic eating outcomes, such as obesity. Craving is a core component of addiction, but there has been little research on the relationship between addictive-like eating, craving, and eating-related concerns. In the current study, we examine the effect of both overall food craving and craving for different types of food on the relationship between addictive-like eating symptoms and elevated body mass index (BMI) and binge eating episodes. METHODS: In a community sample (n=283), we conducted analyses to examine whether overall craving mediated the association between addictive-like eating and elevated BMI, as well as binge eating frequency. We also ran separate mediational models examining the indirect effect of cravings for sweets, fats, carbohydrates, and fast food fats on these same associations. RESULTS: Overall food craving was a significant partial mediator in the relationships between addictive-like eating and both elevated BMI and binge eating episodes. Cravings for sweets and other carbohydrates significantly mediated the relationship between addictive-like eating and binge eating episodes, while cravings for fats significantly mediated the relationship between addictive-like eating and elevated BMI. CONCLUSIONS: Craving appears to be an important component in the pathway between addictive like eating and problematic eating outcomes. The current results highlight the importance of further evaluating the role of an addictive process in problematic eating behaviors and potentially targeting food cravings in intervention approaches. PMID- 26262573 TI - Remarriage after divorce and depression risk. AB - As marriage is associated with lower depression rates compared with being single in men, we aimed to examine if remarriage compared with remaining divorced is also associated with a reduced depression risk. Swedish register data were used to define a cohort of men who were born between 1952 and 1956 and underwent a compulsory military conscription assessment in adolescence. This study population comprised men who were divorced in 1985 (n = 72,246). The risk of pharmaceutically treated depression from 2005 to 2009 was compared for those who remarried or remained divorced between 1986 and 2004. Cox proportional hazards analysis was used to estimate hazard ratios for the risk of depression identified by pharmaceutical treatment, with adjustment for a range of potential confounding factors including childhood and adulthood socioeconomic circumstances, cognitive, physical, psychological and medical characteristics at the conscription assessment. The results showed that, even though divorced men who remarried had markers of lower depression risk in earlier life such as higher cognitive and physical function, higher stress resilience and socioeconomic advantages than men who remained divorced, remarriage was associated with a statistically significant elevated risk of depression with an adjusted hazard ratio (and 95% confidence interval) of 1.27(1.03 1.55), compared with men who remained divorced. Remarriage following divorce is not associated with a reduced risk of depression identified by pharmaceutical treatment, compared with remaining divorced. Interpersonal or financial difficulties resulting from remarriage may outweigh the benefits of marriage in terms of depression risk. PMID- 26262574 TI - Sales promotion strategies and youth drinking in Australia. AB - This study employed an exploratory approach to generate detailed information about how in-store shopping experiences and exposure to sales promotion activities feature in the alcohol choices of Australian 18-21 year old drinkers. The qualitative methods of interviews, focus groups, and emailed narratives were used during 2014 to collect relevant data. The findings suggest that young drinkers' in-store shopping experiences and exposure to sales promotions influence the type, range, and quantity of alcohol purchased. In particular, the role of sales staff can be critical in increasing the amount of alcohol purchased by drawing drinkers' attention to and encouraging their participation in sales promotions. There thus appears to be an important interaction between promotional practices and young drinkers purchasing substantially larger quantities of alcohol than originally intended. Such practices need review in light of the high risk of alcohol-related harm experienced by many members of this age group. PMID- 26262575 TI - Waiting for a baby: Navigating uncertainty in recollections of trying to conceive. AB - OBJECTIVE: Guided by the uncertainty navigation model, this study examined experiences of uncertainty associated with trying to conceive and identified predictors of this experience using a multi-method approach. METHOD: 429 American adults from Amazon's Mechanical Turk who had a child under age three completed online questionnaires regarding their experiences trying to conceive, including recollections of psychological adjustment, use of coping strategies, and individual and situational variability. Then they provided open-ended reflections of their experience trying to conceive. Participants' descriptions were analyzed for word use using LIWC, a text-analysis software program, to obtain an unobtrusive and pseudo-observational measure of coping resources. RESULTS: Consistent with the uncertainty navigation model, recollections of distress as individuals tried to conceive were associated with lower levels of dispositional optimism; intolerance of uncertainty; fewer social, emotional, and cognitive resources (reflected in word use); placing greater importance on conception; lower risk for infertility; and less searching for meaning in life. CONCLUSIONS: This study revealed many novel insights regarding the experience of trying to conceive, including protective factors and vulnerabilities that may buffer or heighten the distress associated with this experience. PMID- 26262576 TI - Formation and Properties of Membrane-Ordered Domains by Phytoceramide: Role of Sphingoid Base Hydroxylation. AB - Phytoceramide is the backbone of major sphingolipids in fungi and plants and is essential in several tissues of animal organisms, such as human skin. Its sphingoid base, phytosphingosine, differs from that usually found in mammals by the addition of a hydroxyl group to the 4-ene, which may be a crucial factor for the different properties of membrane microdomains among those organisms and tissues. Recently, sphingolipid hydroxylation in animal cells emerged as a key feature in several physiopathological processes. Hence, the study of the biophysical properties of phytosphingolipids is also relevant in that context since it helps us to understand the effects of sphingolipid hydroxylation. In this work, binary mixtures of N-stearoyl-phytoceramide (PhyCer) with palmitoyloleoylphosphatidylcholine (POPC) were studied. Steady-state and time resolved fluorescence of membrane probes, X-ray diffraction, atomic force microscopy, and confocal microscopy were employed. As for other saturated ceramides, highly rigid gel domains start to form with just ~5 mol % PhyCer at 24 degrees C. However, PhyCer gel-enriched domains in coexistence with POPC enriched fluid present additional complexity since their properties (maximal order, shape, and thickness) change at specific POPC/PhyCer molar ratios, suggesting the formation of highly stable stoichiometric complexes with their own properties, distinct from both POPC and PhyCer. A POPC/PhyCer binary phase diagram, supported by the different experimental approaches employed, is proposed with complexes of 3:1 and 1:2 stoichiometries which are stable at least from ~15 to ~55 degrees C. Thus, it provides mechanisms for the in vivo formation of sphingolipid-enriched gel domains that may account for stable membrane compartments and diffusion barriers in eukaryotic cell membranes. PMID- 26262577 TI - SAW-based fluid atomization using mass-producible chip devices. AB - Surface acoustic wave (SAW)-based fluid atomizers are ideally suited to generate micrometer-sized droplets without any moving parts or nozzles. Versatile application fields can be found for instance in biomedical, aerosol or thin film technology, including medical inhalators or particle deposition for advanced surface treatment. Such atomizers also show great potential for on-chip integration and can lead to economic production of hand-held and even disposable devices, with either a single functionality or integrated in more complex superior systems. However, this potential was limited in the past by fluid supply mechanisms inadequate for mass production, accuracy and reliability. In this work, we briefly discuss existing fluid supply methods and demonstrate a straightforward new approach suited for reliable and cost-effective mass-scale manufacturing of SAW atomizer chips. Our approach is based on a fluid supply at the boundary of the acoustic beam via SU-8 microchannels produced by a novel one layer/double-exposure photolithography method. Using this technique, we demonstrate precise and stable fluid atomization with almost ideal aerosol plume geometry from a dynamically stabilized thin fluid film. Additionally, we demonstrate the possibility of in situ altering the droplet size distribution by controlling the amount of fluid available in the active region of the chip. PMID- 26262578 TI - Adults with congenital heart disease transition. AB - PURPOSE OF REVIEW: At present, 85-90% of those born with congenital heart disease (CHD) grow up to become adults. With few exceptions, reparative surgery is not curative and requires long-term surveillance. Caregivers could be changed from pediatric cardiologists to adult CHD specialists (or cardiologists) during this process. This study will focus on the current practice of transition in CHD. RECENT FINDINGS: Residua and sequelae may progress in severity with age and induce late complications, such as arrhythmias, cardiac failure, thromboembolism, sudden cardiac death, reoperation, cardiac intervention, and arrhythmia ablation. There are other obstacles that further complicate adult CHD, including pregnancy and delivery, noncardiac surgery, psychosocial problems, health insurance coverage, and extracardiac complications, making close follow-up and proper management mandatory. Because of this, several specialized centers have been established to respond to this need, and several studies focusing on transition have been published recently. SUMMARY: Provision of comprehensive care by multidisciplinary teams including adult CHD specialists, adult and pediatric cardiologists and cardiovascular surgeons, specialized nurses, and other specific disciplines are the fundamental features in care facilities for adult CHD. Training and education should be focused on adult CHD fellows who represent the next generation that will assume responsibility for this patient population. Proper transition from pediatric cardiologists and cardiovascular surgeons to adult CHD care team, including adult CHD specialists and/or cardiologists trained in this field, is mandatory. PMID- 26262580 TI - The vulnerable right ventricle. AB - PURPOSE OF REVIEW: The right ventricle (RV) is uniquely at risk in many patients with repaired or palliated congenital heart disease (CHD) such as tetralogy of Fallot, corrected transposition, single right ventricle, and in those with pulmonary hypertension. These patients live with abnormal cardiac loading conditions throughout their life, predisposing them to right heart failure. RECENT FINDINGS: Standard heart failure therapies, developed to treat left ventricular failure, have failed to improve function or survival in patients with RV failure, suggesting a divergence in the molecular mechanisms of right versus left ventricular failure. As surgical techniques for repair of the most complex forms of RV-affecting CHDs continue to improve, more children with CHD will survive into adulthood. Long-term survival and quality of life will ultimately depend on our ability to preserve RV function. SUMMARY: The purpose of this review is to highlight the differences between the right and left ventricular responses to stress, our current knowledge of how the RV adapts to the unique hemodynamic stressors experienced by patients with CHD, and the need to better understand the molecular mechanisms of RV failure, providing new targets for the development of RV-specific heart failure therapeutics. PMID- 26262579 TI - Computational modeling and engineering in pediatric and congenital heart disease. AB - PURPOSE OF REVIEW: Recent methodological advances in computational simulations are enabling increasingly realistic simulations of hemodynamics and physiology, driving increased clinical utility. We review recent developments in the use of computational simulations in pediatric and congenital heart disease, describe the clinical impact in modeling in single-ventricle patients, and provide an overview of emerging areas. RECENT FINDINGS: Multiscale modeling combining patient specific hemodynamics with reduced order (i.e., mathematically and computationally simplified) circulatory models has become the de-facto standard for modeling local hemodynamics and 'global' circulatory physiology. We review recent advances that have enabled faster solutions, discuss new methods (e.g., fluid structure interaction and uncertainty quantification), which lend realism both computationally and clinically to results, highlight novel computationally derived surgical methods for single-ventricle patients, and discuss areas in which modeling has begun to exert its influence including Kawasaki disease, fetal circulation, tetralogy of Fallot (and pulmonary tree), and circulatory support. SUMMARY: Computational modeling is emerging as a crucial tool for clinical decision-making and evaluation of novel surgical methods and interventions in pediatric cardiology and beyond. Continued development of modeling methods, with an eye towards clinical needs, will enable clinical adoption in a wide range of pediatric and congenital heart diseases. PMID- 26262581 TI - Increased extrafollicular expression of the B-cell stimulatory molecule CD70 in HIV-1-infected individuals. AB - OBJECTIVE: CD70 molecules expressed by activated T cells provide potent B cell stimulatory signals. We hypothesized that an altered CD70 expression might contribute to B cell abnormalities during HIV-1 infection. DESIGN: CD70 expression and the functional and migratory properties of the CD4CD70 T lymphocytes were analyzed in HIV-1-infected patients and in humanized mice. Correlations were tested between CD70 expression and features of B-cell activation, apoptosis sensitivity and functional exhaustion. METHODS: CD4CD70 T cells were analyzed in cohorts of CD4 T-cell lymphopenic, viremic or nonlymphopenic, nonviremic HIV-1-infected patients and in noninfected individuals. CD70 upregulation was also followed in HIV-1-infected humanized mice. CD38, CD95, LAIR1 and PD-1 expressions were monitored on B-cell subpopulations, Ki67 was assessed to estimate B-cell proliferation and antibody levels were measured in plasma. RESULTS: Blood CD4CD70 T-cell frequencies increased in response to CD4 T-cell depletion or high viremia levels as a possible consequence of increased activation and proliferation in this subset. CD4CD70 T cells produced T-helper 1-type cytokines and expressed chemokine receptors mobilizing toward sites of inflammation but not to lymphoid follicles. High CD70 expression was observed in HIV-1-infected humanized mice at extrafollicular sites (peritoneum, bone-marrow). CD4CD70 T-cell frequencies correlated with the expression of the activation marker CD38 and the death receptor CD95 on various memory B-cell subsets, with B-cell proliferation and with plasma IgG levels. CONCLUSIONS: CD4CD70 T cells may contribute to B cell hyperactivation and accelerated memory B-cell turnover during HIV-1 infection. PMID- 26262582 TI - A Spatially Detailed Model of Isometric Contraction Based on Competitive Binding of Troponin I Explains Cooperative Interactions between Tropomyosin and Crossbridges. AB - Biophysical models of cardiac tension development provide a succinct representation of our understanding of force generation in the heart. The link between protein kinetics and interactions that gives rise to high cooperativity is not yet fully explained from experiments or previous biophysical models. We propose a biophysical ODE-based representation of cross-bridge (XB), tropomyosin and troponin within a contractile regulatory unit (RU) to investigate the mechanisms behind cooperative activation, as well as the role of cooperativity in dynamic tension generation across different species. The model includes cooperative interactions between regulatory units (RU-RU), between crossbridges (XB-XB), as well more complex interactions between crossbridges and regulatory units (XB-RU interactions). For the steady-state force-calcium relationship, our framework predicts that: (1) XB-RU effects are key in shifting the half activation value of the force-calcium relationship towards lower [Ca(2+)], but have only small effects on cooperativity. (2) XB-XB effects approximately double the duty ratio of myosin, but do not significantly affect cooperativity. (3) RU RU effects derived from the long-range action of tropomyosin are a major factor in cooperative activation, with each additional unblocked RU increasing the rate of additional RU's unblocking. (4) Myosin affinity for short (1-4 RU) unblocked stretches of actin of is very low, and the resulting suppression of force at low [Ca(2+)] is a major contributor in the biphasic force-calcium relationship. We also reproduce isometric tension development across mouse, rat and human at physiological temperature and pacing rate, and conclude that species differences require only changes in myosin affinity and troponin I/troponin C affinity. Furthermore, we show that the calcium dependence of the rate of tension redevelopment k(tr) is explained by transient blocking of RU's by a temporary decrease in XB-RU effects. PMID- 26262583 TI - Mesothelin-specific cell-based vaccine generates antigen-specific immunity and potent antitumor effects by combining with IL-12 immunomodulator. AB - Ovarian cancer is a gynecologic malignancy with a high mortality rate. In the present study, we developed a novel cell-based vaccine, Meso-VAX, to generate mesothelin antigen-specific immune responses and immunotherapy against ovarian cancer. Mesothelin, a secreted protein anchored at the cell membrane, has recently been identified as a potential new tumor antigen for ovarian cancer. In this study, mice vaccinated with Meso-VAX and adeno-associated virus (AAV)-IL-12 exhibited dramatic increases in the number of mesothelin-specific CD4(+) helper and CD8(+) cytotoxic T-cell precursors, higher titers of anti-mesothelin Abs and in vitro tumor killing activity, and all of these mice were tumor-free after 60 days of tumor challenge. In addition, a significant reduction in peritoneal tumors and longer survival were noted in the mice vaccinated with Meso-VAX combined with AAV-IL-12. CD4(+) helper and CD8(+) cytotoxic T lymphocytes were essential for the antitumor effect generated by Meso-VAX combined with AAV-IL-12. The post-vaccination sera of the mice vaccinated with Meso-VAX and AAV-IL-12 also showed mesothelin-specific complement-dependent cell-mediated cytotoxicity. Our results suggest that a Meso-VAX cell-based vaccine combined with AAV-IL-12 can generate antigen-specific immunological responses and antitumor effects on ovarian cancer. PMID- 26262585 TI - Effect of Preoperative Albumin Levels on Outcomes in Patients Undergoing Left Ventricular Device Implantation. AB - Hypoalbuminemia is a well-known predictor of morbidity and mortality in cardiac surgery. Our aim was to establish the impact of serum albumin on outcomes after left ventricular assist device (LVAD) implantation. This was a single-institution retrospective review, including all patients who underwent LVAD implantation between March 2006 and June 2014. Two hundred patients were included in the analysis. Mean serum albumin was 3.27 +/- 0.47 g/dl, with 7% in the low albumin group (<2.5 mg/dl), 67.5% in the mid-range (2.5-3.5 mg/dl), and 25.5% in the normal albumin groups (> 3.5 mg/dl). Lower albumin was associated with a significant increase in postoperative renal failure (42.9 vs. 16.5 vs. 17.3%; p = 0.05) and prolonged hospitalization (median 28.5 vs. 16 vs. 15.5 days; p = 0.008). Six month, 1 year, and 5 year survival was 79%, 79%, and 49% with low, 84%, 78%, and 51% with mid-range, and 94%, 88%, and 60% with normal albumin, respectively (p = 0.22). Preoperative hypoalbuminemia is associated with postoperative acute renal failure (ARF) and prolonged hospitalization after LVAD implantation, with no effect on overall survival. Hypoalbuminemia is most likely a marker of advanced disease and should not, in itself, be considered a contraindication to LVAD candidacy. PMID- 26262584 TI - Intradermal delivery of DNA encoding HCV NS3 and perforin elicits robust cell mediated immunity in mice and pigs. AB - Currently, no vaccine is available against hepatitis C virus (HCV), and although DNA vaccines have considerable potential, this has not been realised. Previously, the efficacy of DNA vaccines for human immunodeficiency virus (HIV) and HCV was shown to be enhanced by including the gene for a cytolytic protein, viz. perforin. In this study, we examined the mechanism of cell death by this bicistronic DNA vaccine, which encoded the HCV non-structural protein 3 (NS3) under the control of the CMV promoter and perforin is controlled by the SV40 promoter. Compared with a canonical DNA vaccine and a bicistronic DNA vaccine encoding NS3 and the proapoptotic gene NSP4, the perforin-containing vaccine elicited enhanced cell-mediated immune responses against the NS3 protein in vaccinated mice and pigs, as determined by ELISpot and intracellular cytokine staining, whereas a mouse challenge model suggested that the immunity was CD8(+) T-cell-dependent. The results of the study showed that the inclusion of perforin in the DNA vaccine altered the fate of NS3-positive cells from apoptosis to necrosis, and this resulted in more robust immune responses in mice and pigs, the latter of which represents an accepted large animal model in which to test vaccine efficacy. PMID- 26262586 TI - Combination of Exercise Training and Dopamine Agonists in Patients with RLS on Dialysis: A Randomized, Double-Blind Placebo-Controlled Study. AB - Both exercise training and treatment with dopamine agonists (DA) have been used with success for the amelioration of uremic restless legs syndrome (RLS) symptoms. However, no data are available combining those two approaches. The aim of the current randomized, double-blind, placebo-controlled study was to investigate the effects of a 6 month intradialytic exercise training in combination with a low dose of DA in patients suffering from uremic RLS symptoms. Fourteen stable patients with RLS on hemodialysis were randomly assigned to the exercise training plus DA group and the exercise training plus placebo group. Both combinations were found to equally reduce uremic RLS symptoms by approximately 60%. The combination of low dose of DA with aerobic exercise training could be considered an alternative approach to high DA dosage regimes in reducing RLS symptoms' severity. PMID- 26262587 TI - Epidermal Growth Factor Receptor Signaling to the Mitogen Activated Protein Kinase Pathway Bypasses Ras in Pancreatic Cancer Cells. AB - OBJECTIVE: Epidermal growth factor (EGF) receptor (EGFR/HER1) is overexpressed in human pancreatic cancers. However, anti-EGFR therapy does not exhibit significant therapeutic activity with oncogenic K-ras mutation. We sought to assess the signaling relationship between EGFR and mutant K-ras, which is commonly detected in pancreatic cancer. METHODS: Pancreatic cancer cells harboring mutated K-ras were treated with EGF to assess signaling from EGFR to mitogen-activated protein kinase (MAPK) pathway. The role of Ras family of proteins in transducing EGFR signals was assessed using short interfering RNA. Other components of MAPK and PI3K (phosphoinositide 3-kinase) pathways were examined for their roles in EGFR signaling. RESULTS: First, EGF signaling in pancreatic cancer cells occurs selectively through HER1. Second, knockdown of all Ras isoforms failed to block EGF-mediated phosphorylation of extracellular signal-regulated kinase (ERK). Inhibition of Raf was observed to partially abrogate ERK phosphorylation, whereas MEK inhibition resulted in complete attenuation of EGF-mediated ERK phosphorylation. Finally, inhibition of phosphoinositide 3-kinase/AKT and CDC42/PAK pathways did not block EGFR signaling. CONCLUSIONS: Our study results demonstrate that EGFR-mediated signaling in mutant K-ras pancreatic cancer cells does not follow canonical MAPK signaling. Our novel findings suggest the existence of alternate signaling pathways to downstream MAPK in the presence of mutant K-ras. PMID- 26262588 TI - miRNA-21 and miRNA-34a Are Potential Minimally Invasive Biomarkers for the Diagnosis of Pancreatic Ductal Adenocarcinoma. AB - OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly cancers, and its diagnosis often requires invasive procedures. Deregulated miRNA expression has been described in patients with PDAC. In this study, we analyzed the expression levels of 6 miRNAs (miR-21, -34a, -155, -196a, -200b, and -376a involved in PDAC tumorigenesis) in serum and salivary samples to assess their potential role as circulating diagnostics biomarkers. METHODS: Serum and salivary samples were collected from patients with PDAC and healthy controls, and miRNA levels were quantified using qRT-PCR. Twenty-four patients with PDAC and 10 healthy controls were recruited. RESULTS: A significant difference between PDAC and healthy groups was observed for the expression of miR-21 and miR-34a (P < 0.001 and P = 0.001) in serum samples. Both miRNAs accurately discriminated between the 2 groups, with an area under the curve for miR-21 and miR-34a of 0.889 (P = 0.001) and 0.865 (P = 0.002), respectively. In general, the expression of miRNAs between salivary samples did not differ. CONCLUSIONS: Serum miR-21 and miR-34a are potentially useful diagnostic biomarkers of PDAC. In addition, our results suggest that these miRNAs are not differentially expressed in saliva, making them unsuitable for use as noninvasive biomarkers for diagnostic purposes. PMID- 26262589 TI - Predictors for Surgical Referral in Patients With Pancreatic Cystic Lesions Undergoing Endoscopic Ultrasound: Results From a Large Multicenter Cohort Study. AB - OBJECTIVE: Endoscopic ultrasound (EUS) plays an integral role in the evaluation of pancreatic cysts lesions (PCLs). The aim of the study was to determine predictors of surgical referral in patients with PCLs undergoing EUS. METHODS: We performed a multicenter retrospective study of patients undergoing EUS for evaluation of PCLs. Demographics, EUS characteristics, and fine-needle aspiration results were recorded. Patients were categorized into surgery or surveillance groups on the basis of post-EUS recommendations. Univariate and multivariate analyses were performed to identify predictors of surgical referral. RESULTS: 1804 patients were included. 1301 patients were recommended to undergo surveillance and 503 patients were referred for surgical evaluation, of which 360 patients underwent surgery. Multivariate analysis revealed the following 5 independent predictors of surgical referral: symptoms of weight loss on presentation (odds ratio [OR], 2.69; 95% confidence interval [CI], 1.44-5.03), EUS findings of associated solid mass (OR, 7.34; 95% CI, 3.81-14.16), main duct communication (OR, 4.13; 95% CI, 1.71-9.98), multilocular macrocystic morphology (OR, 2.79; 95% CI, 1.78-4.38), and fine-needle aspiration findings of mucin on cytology (OR, 3.06; 95% CI, 1.94-4.82). CONCLUSIONS: This study identifies factors associated with surgical referral in patients with PCLs undergoing EUS. Future studies should focus on creation of risk stratification models to determine the need for surgery or enrollment in surveillance programs. PMID- 26262590 TI - Quantitative Proteomic Analysis of Differentially Expressed Protein Profiles Involved in Pancreatic Ductal Adenocarcinoma. AB - OBJECTIVES: The aim of this study was to identify differentially expressed proteins among various stages of pancreatic ductal adenocarcinoma (PDAC) by shotgun proteomics using nano-liquid chromatography coupled tandem mass spectrometry and stable isotope dimethyl labeling. METHODS: Differentially expressed proteins were identified and compared based on the mass spectral differences of their isotope-labeled peptide fragments generated from protease digestion. RESULTS: Our quantitative proteomic analysis of the differentially expressed proteins with stable isotope (deuterium/hydrogen ratio, >= 2) identified a total of 353 proteins, with at least 5 protein biomarker proteins that were significantly differentially expressed between cancer and normal mice by at least a 2-fold alteration. These 5 protein biomarker candidates include alpha-enolase, alpha-catenin, 14-3-3 beta, VDAC1, and calmodulin with high confidence levels. The expression levels were also found to be in agreement with those examined by Western blot and histochemical staining. CONCLUSIONS: The systematic decrease or increase of these identified marker proteins may potentially reflect the morphological aberrations and diseased stages of pancreas carcinoma throughout progressive developments leading to PDAC. The results would form a firm foundation for future work concerning validation and clinical translation of some identified biomarkers into targeted diagnosis and therapy for various stages of PDAC. PMID- 26262592 TI - Size Effect Suppresses Brittle Failure in Hollow Cu60Zr40 Metallic Glass Nanolattices Deformed at Cryogenic Temperatures. AB - To harness "smaller is more ductile" behavior emergent at nanoscale and to proliferate it onto materials with macroscale dimensions, we produced hollow-tube Cu60Zr40 metallic glass nanolattices with the layer thicknesses of 120, 60, and 20 nm. They exhibit unique transitions in deformation mode with tube-wall thickness and temperature. Molecular dynamics simulations and analytical models were used to interpret these unique transitions in terms of size effects on the plasticity of metallic glasses and elastic instability. PMID- 26262591 TI - Describing Patterns of Care in Pancreatic Cancer: A Population-Based Study. AB - OBJECTIVES: Despite pancreatic cancer being the fifth highest cause of cancer death in developed regions, there is a paucity of population-based management details for patients with pancreatic cancer. The objective of this study was to reflect on current practice and outcomes to facilitate future improvement. METHODS: A comprehensive population-based patterns-of-care study in 2 Australian states was conducted. Patients diagnosed with pancreatic adenocarcinoma between July 2009 and June 2011 were identified by cancer registries, and detailed clinical data were collected from medical records. RESULTS: Data were collected for 1863 patients, 96% of those eligible. The majority resided in major cities; their median age was 72 years, and 54% were men. Over half of the cases (58%) had metastatic disease at diagnosis. Resection was attempted for 20% of patients but only completed in 15%. The uptake of adjuvant chemotherapy (76%) and the proportion alive at 1-year (22%) were higher than reported in previous population based reports. Of those with no complete surgical resection, 43% received palliative chemotherapy. CONCLUSIONS: This population-based overview of the management of patients with pancreatic cancer suggests that, despite evidence that the proportion surviving and the use of adjuvant chemotherapy has increased, there may still be underutilization of cancer-directed therapies. PMID- 26262594 TI - A description of Neoechinorhynchus (Neoechinorhynchus) veropesoi n. sp. (Acanthocephala: Neoechinorhynchidae) from the intestine of the silver croaker fish Plagioscion squamosissimus (Heckel, 1840) (Osteichthyes: Sciaenidae) off the east coast of Brazil. AB - Plagioscion squamosissimus (Heckel, 1840) (Osteichthyes: Sciaenidae) is considered piscivorous and is a generalist species endemic to the Amazon region. This fish is an important part of the natural ecosystems in which it occurs and provides basic functional components in the food web. The genus Neoechinorhynchus Stiles & Hassall, 1905 is distributed worldwide and parasitizes fish and turtles, but there are few reports of parasites of this genus in South America, due to the high diversity of fish that can be found in this region. A new species of thorny headed worm (Acanthocephala: Neoechinorhynchidae) is described from P. squamosissimus from Guajara Bay, Belem, Para, Brazil. In general, the unique characteristics of the hooks on the anterior end of the proboscis and the length to-width ratio relationship separate this new species from other described species in the genus Neoechinorhynchus. Although the species in this genus are mostly found in North America, the dearth of species known from the neotropics may be due to the lack of studies in this region. PMID- 26262593 TI - Genetic diversity and population structure of Synthesium pontoporiae (Digenea, Brachycladiidae) linked to its definitive host stocks, the endangered Franciscana dolphin, Pontoporia blainvillei (Pontoporiidae) off the coast of Brazil and Argentina. AB - Pontoporia blainvillei (Gervais and d'Orbigny, 1844) is an endangered small cetacean endemic to South America with four Franciscana Management Areas (FMA) recognized as different population stocks. The role of the intestinal parasite Synthesium pontoporiae (Digenea: Brachycladiidae) as a possible biological marker to differentiate P. blainvillei stocks was evaluated using nuclear and mitochondrial DNA markers. Internal transcribed sequence 1 and 2 (ITS1 and ITS2) regions of S. pontoporiae did not show intraspecific variability. The mitochondrial NADH dehydrogenase subunit 3 (ND3) and cytochrome oxidase subunit I (COI) gene sequences suggested lack of population structure in S. pontoporiae and population expansion. The apparent panmixia of S. pontoporiae may be due to the high mobility of one or more of its intermediary hosts. Alternatively, it may be due to the small sample size. This result is incongruent with the previously proposed FMA. PMID- 26262595 TI - Single-Step Synthesis of SnS2 Nanosheet-Decorated TiO2 Anatase Nanofibers as Efficient Photocatalysts for the Degradation of Gas-Phase Diethylsulfide. AB - We report on a facile one-step soft hydrothermal process for synthesizing 1D anatase TiO2 nanofibers decorated with ultrathin SnS2 nanosheets. H-titanate nanofibers were used as preshaped Ti precursor. Under controlled conditions, the H-titanate structure was transformed into anatase maintaining the fibril morphology, while at the same time SnS2 nanosheets were grown in situ on the surface of the nanofibers. The successful formation of SnS2 nanosheets on the TiO2 nanofibers was confirmed by high-resolution TEM, and together with XPS spectroscopy, the tight interface formed between the SnS2 and the anatase TiO2 nanofibers was verified. The 1D SnS2/TiO2 hierarchical nanostructures with semiconductor heterojunction were proven to be very efficient under artificial solar irradiation in the photocatalytic degradation of gaseous diethylsulfide as simulant for live yperite chemical warfare agent as well as model substrate for malodorous organosulfide volatile organic compounds. SnS2 did not operate as a visible light sensitizer for TiO2 but rather as an oxidizing agent and charge carrier separator. The semiconductor ratio in the heterostructure controlled the photoactivity. Samples with no or high content of SnS2 were less active than those with moderate SnS2 content. Enhanced reactivity was ascribed to an efficient separation of the photogenerated charge carriers driven by the differences in band edge positions and favored by the tight interface within the coupled heterostructure. PMID- 26262596 TI - Facile Construction of Near Infrared Fluorescence Nanoprobe with Amphiphilic Protein-Polymer Bioconjugate for Targeted Cell Imaging. AB - A simple, straightforward, and reproducible strategy for the construction of a near-infrared (NIR) fluorescence nanoprobe was developed by coating CuInS2/ZnS quantum dots (CIS/ZnS QDs) with a novel amphiphilic bioconjugate. The amphiphilic bioconjugate with a tailor-designed structure of bovine serum albumin (BSA) as the hydrophilic segment and poly(epsilon-caprolactone) (PCL) as the hydrophobic part was fabricated by chemical coupling the hydrophobic polymer chain to BSA via the maleimide-sulfhydryl reaction. By incorporating CIS/ZnS QDs into the hydrophobic cores of the self-assembly of BSA-PCL conjugate, the constructed NIR fluorescence nanoprobe exhibited excellent fluorescent properties over a wide pH range (pH 3-10) and a good colloidal stability in PBS buffer (pH = 7.4) with or without 10% fetal bovine serum. The presence of the outer BSA shell effectively reduced the nonspecific cellular binding and imparted high biocompatibility and low-toxicity to the probe. Moreover, the NIR fluorescence nanoprobe could be functionalized by conjugating cyclic Arg-Gly-Asp (cRGD) peptide, and the decorated nanoprobe was shown to be highly selective for targeted integrin alphavbeta3-overexpressed tumor cell imaging. The feasibility of the constructed NIR fluorescence probe in vivo application was further investigated and the results demonstrated its great potential for in vivo imaging. This developed protocol for phase transfer of the CIS/ZnS QDs was universal and applicable to other nanoparticles stabilized with hydrophobic ligands. PMID- 26262597 TI - Simultaneous determination of six bioactive constituents of Guizhi Fuling Capsule in rat plasma by UHPLC-MS/MS: Application to a pharmacokinetic study. AB - A rapid and selective ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for simultaneous determination of gallic acid, amygdalin, albiflorin, paeoniflorin, paeonol and cinnamic acid, the major bioactive constituents of Guizhi Fuling Capsule in rat plasma using phenacetin as internal standard (IS). The plasma samples were pretreated by protein precipitation with acetonitrile after acidification and separated on a Waters BEH C18 column (50mm*2.1mm, 1.7MUm) using gradient elution with a mobile phase consisting of water (containing 0.1% formic acid) and acetonitrile at a flow rate of 0.2mL/min. Mass spectrometric detection was performed on Micromass Quattromicro API mass spectrometer equipped with electrospray ionization source in multiple reaction monitoring (MRM) mode. The intra- and inter-day precisions (as relative standard deviation) were below 14.6% for all analytes, and the accuracies (as relative error) were within +/-5.0%. The lower limits of quantification (LLOQ) were 10, 10, 5, 5, 25, 25ng/mL for gallic acid, amygdalin, albiflorin, paeoniflorin, paeonol and cinnamic acid, respectively. Extraction recovery, matrix effect and stability were satisfactory in rat plasma. This method was fully validated and applied to a pharmacokinetic study of the six bioactive constituents after oral administration of Guizhi Fuling Capsule to rats. PMID- 26262598 TI - Application of linear multivariate calibration techniques to identify the peaks responsible for the antioxidant activity of Satureja hortensis L. and Oliveria decumbens Vent. essential oils by gas chromatography-mass spectrometry. AB - Satureja hortensis L. and Oliveria decumbens Vent. are known for their diverse effects in drug therapy and traditional medicine. One of the most interesting properties of their essential oils is good antioxidant activity. In this paper, essential oils of aerial parts of S. hortensis L. and O. decumbens Vent. from different regions were obtained by hydrodistillation and were analyzed by gas chromatography-mass spectrometry (GC-MS). Essential oils were tested for their free radical scavenging activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay to identify the peaks potentially responsible for the antioxidant activity from chromatographic fingerprints by numerous linear multivariate calibration techniques. Because of its simplicity and high repeatability, orthogonal projection to latent structures (OPLS) model had the best performance in indicating the potential antioxidant compounds in S. hortensis L. and O. decumbens Vent. essential oils. In this study, P-cymene, carvacrol and beta bisabolene for S. hortensis L. and P-cymene, C-terpinen, thymol, carvacrol, and 1,3-benzodioxole, 4-methoxy-6-(2-propenyl) for O. decumbens Vent. are suggested as the potentially antioxidant compounds. PMID- 26262599 TI - Separation of phenolic acids and flavonoids from Trollius chinensis Bunge by high speed counter-current chromatography. AB - In this work, eleven compounds were successfully separated from Trollius chinensis Bunge by using a two-step high-speed counter-current chromatography (HSCCC) method. NRTL-SAC (nonrandom two-liquid segment activity coefficient) method, a newly developed solvent system selection strategy, was applied to screening the suitable biphasic liquid systems. Hexane/ethyl acetate/ethanol/water (3:7:3:7, v/v) solvent system was used in the first step, while the hexane/ethyl acetate/methanol/water (1:2:1:2, 1:4:1:4, 1:9:1:9, v/v) systems were employed in the second step. The chemical structures of the separated compounds were identified by UV, high resolution ESI-MS and MS/MS data. The separated compounds are 3,4-dihydroxyphenylethanol (1), vanillic acid (2), orientin (3), vitexin (4), veratric acid (5), 2"-O-(3''', 4'''-dimethoxybenzoyl) orientin (6), 2"-O-feruloylorientin (7), 2"-O-feruloylvitexin (8), 2"-O-(2''' methylbutyryl) vitexin (9), 2"-O-(2'''-methylbutyryl) isoswertiajaponin (10), 2" O-(2'''-methylbutyryl) isoswertisin (11). The results demonstrate that HSCCC is a powerful tool for the separation of compounds from extremely complex samples. PMID- 26262600 TI - Tissue distribution, excretion, and the metabolic pathway of 2,2',4,4',5-penta chlorinated diphenylsulfide (CDPS-99) in ICR mice. AB - The tissue distribution, excretion, and metabolic pathway of 2,2',4,4',5-penta chlorinated diphenylsulfide (CDPS-99) in ICR mice were investigated after oral perfusion at 10mg/kg body weight (b.w.). Biological samples were extracted and separated and, for the first time, were determined by a novel, sensitive, and specific GC-MS method under the full scan and selected ion monitoring (SIM) modes. The results showed that the concentrations of CDPS-99 in the liver, kidneys, and serum reached a maximum after a one-day exposure and that the CDPS 99 concentration in the liver was the highest (3.43MUg/g). The increase in the concentration of CDPS-99 in muscle, skin, and adipose tissue was slower, and the concentrations of CDPS-99 achieved their highest levels after 3 days of exposure. It was observed that the CDPS-99 concentration in adipose tissue was still very high (0.71MUg/g) after 21 days of exposure, which suggested that CDPS-99 was able to accumulate in adipose tissue. In addition, mouse feces accounted for approximately 75% of the total gavage dose, indicating that CDPS-99 was mainly excreted via mouse feces. Metabolism analysis demonstrated that there were three possible metabolic pathways of CDPS-99 in mice: dechlorination reactions with the formation of tetra-CDPS and hydroxylation and oxidation reactions with the formation of OH-CDPS-99 and chlorinated diphenylsulfone. The present study will help to develop a better understanding of mammalian metabolism of CDPS-99. PMID- 26262601 TI - UPLC-Q-TOF/MS-based screening and identification of two major bioactive components and their metabolites in normal and CKD rat plasma, urine and feces after oral administration of Rehmannia glutinosa Libosch extract. AB - Rehmannia glutinosa is a widely used traditional Chinese medicine (TCM) in clinical practice to tackle chronic kidney disease for thousands of years. However, the in vivo metabolism of its two major bioactive components (catalpol and acteoside) remains unknown. In this paper, a highly sensitive, rapid and robust ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) with MetaboLynxTM software combined with mass defect filtering (MDF) method was established. This validated analysis method was successfully applied to investigate the in vivo metabolic profiles of R. glutinosa extract in normal and chronic kidney disease (CKD) rats. The results showed that a total of 17 metabolites of two parent compounds in normal rats in vivo were tentatively detected and identified according to the characteristics of their protonated ions and relevant literature. While 11 of the metabolites were observed in the CKD rat samples. These metabolites suggested that catalpol was firstly deglycosylated to its aglycone and subsequently to two main metabolites (M1 and M4) by conjugation and hydrogenation respectively and acteoside was mainly metabolized by O-glucuronide conjugation and O-sulphate conjugation. In conclusion, this study showed an insight into the metabolism of R. glutinosa extract in vivo and the proposed metabolic pathways of bioactive components might play a key role in further pharmacokinetic experiments evaluations. PMID- 26262602 TI - Simultaneous determination of cinnamaldehyde, cinnamic acid, and 2-methoxy cinnamic acid in rat whole blood after oral administration of volatile oil of Cinnamoni Ramulus by UHPLC-MS/MS: An application for a pharmacokinetic study. AB - A simple and rapid ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the simultaneous determination of cinnamaldehyde, cinnamic acid, and 2-methoxy cinnamic acid in rat whole blood. It was the first time to study the pharmacokinetics of 2-methoxy cinnamic acid in rat whole blood. Samples were processed by a one-step protein precipitation with acetonitrile-37% formaldehyde (90:10, v:v). Chromatographic separation was performed on a Thermo Scientific C18 column (2.1mm*50mm, 1.9MUm) at room temperature. The total run time was 4min. The detection was accomplished by using positive and negative ion electrospray ionization in multiple reaction monitoring mode. The method was linear for all of the analytes over 1000 times concentration range with correlation coefficients greater than 0.99. The lower limits of quantification (LLOQ) were 0.1ng/mL for cinnamaldehyde, 5.8ng/mL for cinnamic acid, and 10ng/mL for 2-methoxy cinnamic acid, respectively. To our knowledge, this was the first time that the LLOQ for cinnamaldehyde in validated methods for biological samples was as low as 0.1ng/mL. Intra- and inter-day precision and accuracy were within +/-9% for all of the analytes during the assay validation. Assay recoveries were higher than 80% and the matrix effects were minimal. The half-life were 8.7+/-0.7h for cinnamaldehyde, 1.0+/-0.5h for cinnamic acid, and 1.4+/-0.4h for 2-methoxy cinnamic acid, respectively. The validated assay was firstly applied to the simultaneous quantification of cinnamaldehyde, cinnamic acid, and 2-methoxy cinnamic acid, especially for 2 methoxy cinnamic acid in rat whole blood after oral administration of 15mg/kg essential oil of Cinnamoni Ramulus. It was observed that the Cmax and AUC of 2 methoxy cinnamic acid (0.01% in essential oil of Cinnamoni Ramulus) were greater than those of cinnamaldehyde (83.49% in essential oil of Cinnamoni Ramulus), which implied that 2-methoxy cinnamic acid might be the major bioactive constitutes in essential oil of Cinnamoni Ramulus. PMID- 26262603 TI - Synergy of Cobalt and Silver Microparticles Electrodeposited on Glassy Carbon for the Electrocatalysis of the Oxygen Reduction Reaction: An Electrochemical Investigation. AB - The combination of two different metals, each of them acting on different steps of the oxygen reduction reaction (ORR), yields synergic catalytic effects. In this respect, the electrocatalytic effect of silver is enhanced by the addition of cobalt, which is able to break the O-O bond of molecular oxygen, thus accelerating the first step of the reduction mechanism. At the same time, research is to further reduce the catalyst's cost, reducing the amount of Ag, which, even though being much less expensive than Pt, is still a noble metal. From this point of view, using a small amount of Ag together with an inexpensive material, such as graphite, represents a good compromise. The aim of this work was to verify if the synergic effects are still operating when very small amounts of cobalt (2-10 MUg.cm(-2)) are added to the microparticles of silver electrodeposited on glassy carbon, described in a preceding paper from us. To better stress the different behaviour observed when cobalt and silver are contemporarily present in the deposit, the catalytic properties of cobalt alone were investigated. The analysis was completed by the Levich plots to evaluate the number of electrons involved and by Tafel plots to show the effects on the reaction mechanism. PMID- 26262604 TI - Mentha spicata Essential Oil: Chemical Composition, Antioxidant and Antibacterial Activities against Planktonic and Biofilm Cultures of Vibrio spp. Strains. AB - Chemical composition, antioxidant and anti-Vibrio spp. activities of the essential oil isolated from the aerial parts of Mentha spicata L. (spearmint) are investigated in the present study. The effect of the essential oil on Vibrio spp. biofilm inhibition and eradication was tested using the XTT assay. A total of 63 chemical constituents were identified in spearmint oil using GC/MS, constituting 99.9% of the total identified compounds. The main components were carvone (40.8% +/- 1.23%) and limonene (20.8% +/- 1.12%). The antimicrobial activity against 30 Vibrio spp. strains (16 species) was evaluated by disc diffusion and microdilution assays. All microorganisms were strongly affected, indicating an appreciable antimicrobial potential of the oil. Moreover, the investigated oil exhibited high antioxidant potency, as assessed by four different tests in comparison with BHT. The ability of the oil, belonging to the carvone chemotype, to inhibit or reduce Vibrio spp. biofilm warrants further investigation to explore the use of natural products in antibiofilm adhesion and reinforce the possibility of its use in the pharmaceutical or food industry as a natural antibiotic and seafood preservative against Vibrio contamination. PMID- 26262605 TI - Management of Hyperglycaemia by Ethyl Acetate Extract of Balanites aegyptiaca (Desert Date). AB - Reactive oxygen species play a significant role in the pathogenesis of retinopathy in diabetes patients. The current study aimed to assess the effect of ethyl acetate extract (EAE) from Balanites aegyptiaca (10, 25 or 50 mg/kg b.w.) in experimental diabetic rats. To achieve this aim, five groups of male rats were included: control, diabetic, and diabetic rats treated with 10, 25, and 50 ug/kg b.w. of EAE for eight weeks. Our results suggests a protective role of EAE against oxidative stress induced by streptozocine. EAE treatment produced a reduction in blood glucose levels, HbA1c, malondialdehyde and vascular endothelial growth factor (VEGF) in diabetic retina (p < 0.001), as well as an enhancement in antioxidant capacity against streptozocine-induced oxidative stress. Tumor necrosis factor alpha (TNF-alpha), interleukin (IL-1beta) and vascular endothelial growth factor (VEGF) were significantly reduced in diabetic rats treated with EAE, compared with untreated diabetic rats. Analysis of EAE by GC-MS indicated the presence of beta-sistosterol. Overall, EAE modulates oxidative stress induced by streptozocine and enhances antioxidant activity, which may provide additional endothelial protection in retina of diabetic rats. These results hold great promise in the management of diabetic complications. PMID- 26262606 TI - Molecular Structures of the Products of a Diphosphonate Ester Building Block with Lewis Bases. AB - By treating a suitable Wittig reagent under acid conditions, the phosphonate ester 1,4-bimethylenebenzene phosphonate ethyl ester (H2[BBPE], 1) was obtained. As a building block, compound 1 has been reacted with the Lewis-base N,N dimethylpiperazine, ammonia and NaOH yielded compounds 2-4. The crystal structures show that a 1D chain forming a tubular channel is constructed through hydrogen bonds in 1; hydrogen bonds form two 1D chains with left-hand and right hand helixes and form 3D networks in compound 2; 1D hydrogen-bond chains are further connected together to afford a 3D network architecture in compound 3; the phosphonate is coordinated by two Na atoms which present different coordination environments in compound 4. Additionally, the relationships between the structure and fluorescence of the four compounds in the solid state and in different solvents have also been studied at room temperature. PMID- 26262607 TI - Chitosan in Molecularly-Imprinted Polymers: Current and Future Prospects. AB - Chitosan is widely used in molecular imprinting technology (MIT) as a functional monomer or supporting matrix because of its low cost and high contents of amino and hydroxyl functional groups. The various excellent properties of chitosan, which include nontoxicity, biodegradability, biocompatibility, and attractive physical and mechanical performances, make chitosan a promising alternative to conventional functional monomers. Recently, chitosan molecularly-imprinted polymers have gained considerable attention and showed significant potential in many fields, such as curbing environmental pollution, medicine, protein separation and identification, and chiral-compound separation. These extensive applications are due to the polymers' desired selectivity, physical robustness, and thermal stability, as well as their low cost and easy preparation. Cross linkers, which fix the functional groups of chitosan around imprinted molecules, play an important role in chitosan molecularly-imprinted polymers. This review summarizes the important cross-linkers of chitosan molecularly-imprinted polymers and illustrates the cross-linking mechanism of chitosan and cross-linkers based on the two glucosamine units. Finally, some significant attempts to further develop the application of chitosan in MIT are proposed. PMID- 26262610 TI - Hesperidin, A Popular Antioxidant Inhibits Melanogenesis via Erk1/2 Mediated MITF Degradation. AB - Regulation of melanogenesis has been the focus of treatment for hyperpigmentary skin disorders. Although hesperidin is one of the most well-known, naturally occurring flavonoids with antioxidant and anti-inflammatory effect, its anti melanogenic effect is not known. The present study aims to determine the anti melanogenic effect of hespiridin as well as its underlying molecular mechanisms. Melanin contents were measured in normal human melanocytes and B16F10 melanoma cells. Protein and mRNA levels of tyrosinase, microphthalmia-associated transcription factor (MITF), tyrosinase related protein-1 (TRP-1) and TRP-2 were determined. Melanogenesis-regulating signals were examined. In results, hesperidin strongly inhibited melanin synthesis and tyrosinase activity. Hesperidin decreased tyrosinase, TRP-1, and TRP-2 protein expression but increased phospho-extracellular signal-regulated kinase 1/2 (p-Erk1/2) expression. Specific inhibitor of Erk1/2 or proteasome inhibitor reversed the inhibition of melanogenesis induced by hesperidin. Taken together, hesperidin, a popular antioxidant, stimulated Erk1/2 phosphorylation which subsequently degraded MITF which resulted in suppression of melanogenic enzymes and melanin synthesis. PMID- 26262608 TI - Overview of Nrf2 as Therapeutic Target in Epilepsy. AB - Oxidative stress is a biochemical state of imbalance in the production of reactive oxygen and nitrogen species and antioxidant defenses. It is involved in the physiopathology of degenerative and chronic neuronal disorders, such as epilepsy. Experimental evidence in humans and animals support the involvement of oxidative stress before and after seizures. In the past few years, research has increasingly focused on the molecular pathways of this process, such as that involving transcription factor nuclear factor E2-related factor 2 (Nrf2), which plays a central role in the regulation of antioxidant response elements (ARE) and modulates cellular redox status. The aim of this review is to present experimental evidence on the role of Nrf2 in this neurological disorder and to further determine the therapeutic impact of Nrf2 in epilepsy. PMID- 26262609 TI - The Essential Role of Vitellogenin Receptor in Ovary Development and Vitellogenin Uptake in Bactrocera dorsalis (Hendel). AB - The vitellogenin receptor (VgR) functions as an essential component in uptaking and transporting vitellogenin (Vg) in female adults, which is involved in ovary development and oviposition. This study aimed to clarify the molecular characteristics and function of VgR in the oriental fruit fly Bactrocera dorsalis (Hendel). Here, we identified the full-length of BdVgR (GenBank Accession No. JX469118), encoding a 1925 residue (aa) protein with a 214.72 kDa molecular mass and several typical motifs of low-density lipoprotein receptor superfamily (LDLR). Phylogenic analysis suggested that BdVgR was evolutionary conserved with other Dipteran VgRs. The expression of BdVgR was exclusively detected in the ovaries rather than head, thorax or other tissues. The developmental expression patterns showed that the signal of BdVgR was detectable in very beginning of adult stage, and positively correlated with the growth rate of ovaries and the expression levels of its ligands. In addition, we also demonstrated that the expression level of BdVgR, and ovary development were significantly suppressed after being injected with BdVgR-targeted dsRNA. Together, all of these results indicated that BdVgR was critical for yolk protein absorption and ovary maturation in B. dorsalis, playing a vital role in female reproduction. PMID- 26262611 TI - Permeability Study of Polyphenols Derived from a Phenolic-Enriched Hibiscus sabdariffa Extract by UHPLC-ESI-UHR-Qq-TOF-MS. AB - Previous findings on the capacity of Hibiscus sabdariffa (HS) polyphenols to ameliorate metabolic disturbances justify the necessity of studies oriented to find the potential metabolites responsible for such an effect. The present study examined the intestinal epithelial membrane permeability of polyphenols present in a phenolic-enriched Hibiscus sabdariffa extract (PEHS), free and encapsulated, using the Caco-2 cell line. Additionally, selected polyphenols (quercetin, quercetin-3-glucoside, quercetin-3-glucuronide, and N-feruloyltyramine) were also studied in the same absorption model. The powerful analytical platform used ultra high-performance liquid chromatography coupled with ultra-high-resolution quadrupole time-of-flight mass spectrometry (UHPLC-ESI-UHR-Qq-TOF-MS), and enabled the characterization of seven new compounds in PEHS. In the permeation study, only a few compounds were able to cross the cell monolayer and the permeability was lower when the extract was in an encapsulated form. Pure compounds showed a moderate absorption in all cases. Nevertheless, these preliminary results may need further research to understand the complete absorption mechanism of Hibiscus polyphenols. PMID- 26262612 TI - Polymodal Transient Receptor Potential Vanilloid (TRPV) Ion Channels in Chondrogenic Cells. AB - Mature and developing chondrocytes exist in a microenvironment where mechanical load, changes of temperature, osmolarity and acidic pH may influence cellular metabolism. Polymodal Transient Receptor Potential Vanilloid (TRPV) receptors are environmental sensors mediating responses through activation of linked intracellular signalling pathways. In chondrogenic high density cultures established from limb buds of chicken and mouse embryos, we identified TRPV1, TRPV2, TRPV3, TRPV4 and TRPV6 mRNA expression with RT-PCR. In both cultures, a switch in the expression pattern of TRPVs was observed during cartilage formation. The inhibition of TRPVs with the non-selective calcium channel blocker ruthenium red diminished chondrogenesis and caused significant inhibition of proliferation. Incubating cell cultures at 41 degrees C elevated the expression of TRPV1, and increased cartilage matrix production. When chondrogenic cells were exposed to mechanical load at the time of their differentiation into matrix producing chondrocytes, we detected increased mRNA levels of TRPV3. Our results demonstrate that developing chondrocytes express a full palette of TRPV channels and the switch in the expression pattern suggests differentiation stage-dependent roles of TRPVs during cartilage formation. As TRPV1 and TRPV3 expression was altered by thermal and mechanical stimuli, respectively, these are candidate channels that contribute to the transduction of environmental stimuli in chondrogenic cells. PMID- 26262613 TI - Identification of Hydroxyanthraquinones as Novel Inhibitors of Hepatitis C Virus NS3 Helicase. AB - Hepatitis C virus (HCV) is an important etiological agent of severe liver diseases, including cirrhosis and hepatocellular carcinoma. The HCV genome encodes nonstructural protein 3 (NS3) helicase, which is a potential anti-HCV drug target because its enzymatic activity is essential for viral replication. Some anthracyclines are known to be NS3 helicase inhibitors and have a hydroxyanthraquinone moiety in their structures; mitoxantrone, a hydroxyanthraquinone analogue, is also known to inhibit NS3 helicase. Therefore, we hypothesized that the hydroxyanthraquinone moiety alone could also inhibit NS3 helicase. Here, we performed a structure-activity relationship study on a series of hydroxyanthraquinones by using a fluorescence-based helicase assay. Hydroxyanthraquinones inhibited NS3 helicase with IC50 values in the micromolar range. The inhibitory activity varied depending on the number and position of the phenolic hydroxyl groups, and among different hydroxyanthraquinones examined, 1,4,5,8-tetrahydroxyanthraquinone strongly inhibited NS3 helicase with an IC50 value of 6 uM. Furthermore, hypericin and sennidin A, which both have two hydroxyanthraquinone-like moieties, were found to exert even stronger inhibition with IC50 values of 3 and 0.8 uM, respectively. These results indicate that the hydroxyanthraquinone moiety can inhibit NS3 helicase and suggest that several key chemical structures are important for the inhibition. PMID- 26262614 TI - Novel Electrocardiographic Patterns for the Prediction of Hypertensive Disorders of Pregnancy--From Pathophysiology to Practical Implications. AB - Hypertensive disorders of pregnancy are a major cause of poor outcome, including placental abruption, organ failure, cerebrovascular accident and disseminated intravascular coagulation. These disorders are associated with increased fetal risk of intrauterine growth restriction, intrauterine death and prematurity. Electrocardiography (ECG) recently emerged as a useful tool to evaluate cardiovascular complications during pregnancy. Specifically, left atrial abnormalities detected by standard ECG are associated with a fourfold increased risk of developing hypertensive disorders during pregnancy. The mechanisms linking left atrial abnormality on ECG with hypertensive disorders are still elusive. Several mechanisms, possibly reflected by abnormal left atrial activation on ECG, has been suggested. These include increased reactivity to angiotensin II and up-regulation of angiotensin type 1 receptors, with activation of autoantibodies targeting these receptors. PMID- 26262616 TI - Differentiation Effects of Platelet-Rich Plasma Concentrations on Synovial Fluid Mesenchymal Stem Cells from Pigs Cultivated in Alginate Complex Hydrogel. AB - This article studied the effects of platelet-rich plasma (PRP) on the potential of synovial fluid mesenchymal stem cells (SF-MSCs) to differentiate. The PRP and SF-MSCs were obtained from the blood and knees of pigs, respectively. The identification of SF-MSCs and their ability to differentiate were studied by histological and surface epitopes, respectively. The SF-MSCs can undergo trilineage mesenchymal differentiation under osteogenic, chondrogenic, and adipocyte induction. The effects of various PRP concentrations (0%, 20% and 50% PRP) on differentiation were evaluated using the SF-MSCs-alginate system, such as gene expression and DNA proliferation. A 50% PRP concentration yielded better differentiation than the 20% PRP concentration. PRP favored the chondrogenesis of SF-MSCs over their osteogenesis in a manner that depended on the ratios of type II collagen/type I collagen and aggrecan/osteopontin. Eventually, PRP promoted the proliferation of SF-MSCs and induced chondrogenic differentiation of SF-MSCs in vitro. Both PRP and SF-MSCs could be feasibly used in regenerative medicine and orthopedic surgeries. PMID- 26262617 TI - Comparison of Soybean Transformation Efficiency and Plant Factors Affecting Transformation during the Agrobacterium Infection Process. AB - The susceptibility of soybean genotype to Agrobacterium infection is a key factor for the high level of genetic transformation efficiency. The objective of this study is to evaluate the plant factors related to transformation in cotyledonary nodes during the Agrobacterium infection process. This study selected three genotypes (Williams 82, Shennong 9 and Bert) with high transformation efficiency, which presented better susceptibility to Agrobacterium infection, and three low transformation efficiency genotypes (General, Liaodou 16 and Kottman), which showed a relatively weak susceptibility. Gibberellin (GA) levels and soybean GA20ox2 and CYP707A2 transcripts of high-efficiency genotypes increased and were higher than those of low-efficiency genotypes; however, the opposite performance was shown in abscisic acid (ABA). Higher zeatin riboside (ZR) content and DNA quantity, and relatively higher expression of soybean IPT5, CYCD3 and CYCA3 were obtained in high-efficiency genotypes. High-efficiency genotypes had low methyl jasmonate (MeJA) content, polyphenol oxidase (PPO) and peroxidase (POD) activity, and relatively lower expression of soybean OPR3, PPO1 and PRX71. GA and ZR were positive plant factors for Agrobacterium-mediated soybean transformation by facilitating germination and growth, and increasing the number of cells in DNA synthesis cycle, respectively; MeJA, PPO, POD and ABA were negative plant factors by inducing defence reactions and repressing germination and growth, respectively. PMID- 26262615 TI - Functional Selectivity and Antidepressant Activity of Serotonin 1A Receptor Ligands. AB - Serotonin (5-HT) is a monoamine neurotransmitter that plays an important role in physiological functions. 5-HT has been implicated in sleep, feeding, sexual behavior, temperature regulation, pain, and cognition as well as in pathological states including disorders connected to mood, anxiety, psychosis and pain. 5-HT1A receptors have for a long time been considered as an interesting target for the action of antidepressant drugs. It was postulated that postsynaptic 5-HT1A agonists could form a new class of antidepressant drugs, and mixed 5-HT1A receptor ligands/serotonin transporter (SERT) inhibitors seem to possess an interesting pharmacological profile. It should, however, be noted that 5-HT1A receptors can activate several different biochemical pathways and signal through both G protein-dependent and G protein-independent pathways. The variables that affect the multiplicity of 5-HT1A receptor signaling pathways would thus result from the summation of effects specific to the host cell milieu. Moreover, receptor trafficking appears different at pre- and postsynaptic sites. It should also be noted that the 5-HT1A receptor cooperates with other signal transduction systems (like the 5-HT1B or 5-HT2A/2B/2C receptors, the GABAergic and the glutaminergic systems), which also contribute to its antidepressant and/or anxiolytic activity. Thus identifying brain specific molecular targets for 5-HT1A receptor ligands may result in a better targeting, raising a hope for more effective medicines for various pathologies. PMID- 26262619 TI - Ultrasonic Technique for Density Measurement of Liquids in Extreme Conditions. AB - An ultrasonic technique, invariant to temperature changes, for a density measurement of different liquids under in situ extreme conditions is presented. The influence of geometry and material parameters of the measurement system (transducer, waveguide, matching layer) on measurement accuracy and reliability is analyzed theoretically along with experimental results. The proposed method is based on measurement of the amplitude of the ultrasonic wave, reflected from the interface of the solid/liquid medium under investigation. In order to enhance sensitivity, the use of a quarter wavelength acoustic matching layer is proposed. Therefore, the sensitivity of the measurement system increases significantly. Density measurements quite often must be performed in extreme conditions at high temperature (up to 220 degrees C) and high pressure. In this case, metal waveguides between piezoelectric transducer and the measured liquid are used in order to protect the conventional transducer from the influence of high temperature and to avoid depolarization. The presented ultrasonic density measurement technique is suitable for density measurement in different materials, including liquids and polymer melts in extreme conditions. A new calibration algorithm was proposed. The metrological evaluation of the measurement method was performed. The expanded measurement uncertainty Urho = 7.4 * 10(-3) g/cm(3) (1%). PMID- 26262618 TI - SCM-198 Ameliorates Cognitive Deficits, Promotes Neuronal Survival and Enhances CREB/BDNF/TrkB Signaling without Affecting Abeta Burden in AbetaPP/PS1 Mice. AB - SCM-198 is an alkaloid found only in Herba leonuri and it has been reported to possess considerable neuroprotective effects in animal models of ischemic stroke, Parkinson's disease and Alzheimer's disease (AD). In this study, we demonstrated for the first time that 3-month oral SCM-198 treatment could significantly improve both recognition and spatial memory, inhibit microgliosis and promote neuronal survival in amyloid-beta protein precursor and presenilin-1(AbetaPP/PS1) double-transgenic mice without affecting amyloid-beta (Abeta) burden. In addition, decreases in cAMP-response element-binding protein (CREB) phosphorylation, brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) phosphorylation were attenuated by SCM-198 both in vivo and in primary cortical neurons, which could be blocked by protein kinase A (PKA) inhibitors, suggesting the involvement of upstream PKA in enhancing the BDNF/TrkB/CREB signaling by SCM-198. Our results indicate that SCM-198, a drug that could promote neuronal survival and enhance BDNF/TrkB/CREB signaling, has beneficial effects on behavioral and biochemical alterations without affecting Abeta burden in AbetaPP/PS1 mice and might become a potential drug candidate for AD treatment in the future. PMID- 26262620 TI - Ocean Wave Separation Using CEEMD-Wavelet in GPS Wave Measurement. AB - Monitoring ocean waves plays a crucial role in, for example, coastal environmental and protection studies. Traditional methods for measuring ocean waves are based on ultrasonic sensors and accelerometers. However, the Global Positioning System (GPS) has been introduced recently and has the advantage of being smaller, less expensive, and not requiring calibration in comparison with the traditional methods. Therefore, for accurately measuring ocean waves using GPS, further research on the separation of the wave signals from the vertical GPS mounted carrier displacements is still necessary. In order to contribute to this topic, we present a novel method that combines complementary ensemble empirical mode decomposition (CEEMD) with a wavelet threshold denoising model (i.e., CEEMD Wavelet). This method seeks to extract wave signals with less residual noise and without losing useful information. Compared with the wave parameters derived from the moving average skill, high pass filter and wave gauge, the results show that the accuracy of the wave parameters for the proposed method was improved with errors of about 2 cm and 0.2 s for mean wave height and mean period, respectively, verifying the validity of the proposed method. PMID- 26262621 TI - Electrochemical Characterization of Protein Adsorption onto YNGRT-Au and VLGXE-Au Surfaces. AB - The adsorption of the proteins CD13, mucin and bovine serum albumin on VLGXE-Au and YNGRT-Au interfaces was monitored by electrochemical impedance spectroscopy in the presence of [Fe(CN)6](3-/4-). The hydrophobicity of the Au surface was tailored using specific peptides, blocking agents and diluents. The combination of blocking agents (ethanolamine or n-butylamine) and diluents (hexanethiol or 2 mercaptoethanol) was used to prepare various peptide-modified Au surfaces. Protein adsorption onto the peptide-Au surfaces modified with the combination of n-butylamine and hexanethiol produced a dramatic decrease in the charge transfer resistance, Rct, for all three proteins. In contrast, polar peptide-surfaces induced a minimal change in Rct for all three proteins. Furthermore, an increase in Rct was observed with CD13 (an aminopeptidase overexpressed in certain cancers) in comparison to the other proteins when the VLGXE-Au surface was modified with n-butylamine as a blocking agent. The electrochemical data indicated that protein adsorption may be modulated by tailoring the peptide sequence on Au surfaces and that blocking agents and diluents play a key role in promoting or preventing protein adsorption. The peptide-Au platform may also be used for targeting cancer biomarkers with designer peptides. PMID- 26262622 TI - An Efficient Data Compression Model Based on Spatial Clustering and Principal Component Analysis in Wireless Sensor Networks. AB - Wireless sensor networks (WSNs) have been widely used to monitor the environment, and sensors in WSNs are usually power constrained. Because inner-node communication consumes most of the power, efficient data compression schemes are needed to reduce the data transmission to prolong the lifetime of WSNs. In this paper, we propose an efficient data compression model to aggregate data, which is based on spatial clustering and principal component analysis (PCA). First, sensors with a strong temporal-spatial correlation are grouped into one cluster for further processing with a novel similarity measure metric. Next, sensor data in one cluster are aggregated in the cluster head sensor node, and an efficient adaptive strategy is proposed for the selection of the cluster head to conserve energy. Finally, the proposed model applies principal component analysis with an error bound guarantee to compress the data and retain the definite variance at the same time. Computer simulations show that the proposed model can greatly reduce communication and obtain a lower mean square error than other PCA-based algorithms. PMID- 26262623 TI - A High Performance Delta-Sigma Modulator for Neurosensing. AB - Recorded neural data are frequently corrupted by large amplitude artifacts that are triggered by a variety of sources, such as subject movements, organ motions, electromagnetic interferences and discharges at the electrode surface. To prevent the system from saturating and the electronics from malfunctioning due to these large artifacts, a wide dynamic range for data acquisition is demanded, which is quite challenging to achieve and would require excessive circuit area and power for implementation. In this paper, we present a high performance Delta-Sigma modulator along with several design techniques and enabling blocks to reduce circuit area and power. The modulator was fabricated in a 0.18-um CMOS process. Powered by a 1.0-V supply, the chip can achieve an 85-dB peak signal-to-noise-and distortion ratio (SNDR) and an 87-dB dynamic range when integrated over a 10-kHz bandwidth. The total power consumption of the modulator is 13 uW, which corresponds to a figure-of-merit (FOM) of 45 fJ/conversion step. These competitive circuit specifications make this design a good candidate for building high precision neurosensors. PMID- 26262624 TI - Signal Transducers and Activators of Transcription (STAT) Regulatory Networks in Marine Organisms: From Physiological Observations towards Marine Drug Discovery. AB - Part of our ocean's richness comes from its extensive history of supporting life, resulting in a highly diverse ecological system. To date, over 250,000 species of marine organisms have been identified, but it is speculated that the actual number of marine species exceeds one million, including several hundreds of millions of species of marine microorganisms. Past studies suggest that approximately 70% of all deep-sea microorganisms, gorgonians, and sea sponges produce secondary metabolites with anti-cancer activities. Recently, novel FDA approved drugs derived from marine sponges have been shown to reduce metastatic breast cancer, malignant lymphoma, and Hodgkin's disease. Despite the fact that many marine natural products have been shown to possess a good inhibition potential against most of the cancer-related cell signaling pathways, only a few marine natural products have been shown to target JAK/STAT signaling. In the present paper, we describe the JAK/STAT signaling pathways found in marine organisms, before elaborating on the recent advances in the field of STAT inhibition by marine natural products and the potential application in anti cancer drug discovery. PMID- 26262625 TI - Lipopolysaccharides from Commensal and Opportunistic Bacteria: Characterization and Response of the Immune System of the Host Sponge Suberites domuncula. AB - Marine sponges harbor a rich bacterioflora with which they maintain close relationships. However, the way these animals make the distinction between bacteria which are consumed to meet their metabolic needs and opportunistic and commensal bacteria which are hosted is not elucidated. Among the elements participating in this discrimination, bacterial cell wall components such as lipopolysaccharides (LPS) could play a role. In the present study, we investigated the LPS chemical structure of two bacteria associated with the sponge Suberites domuncula: a commensal Endozoicomonas sp. and an opportunistic Pseudoalteromonas sp. Electrophoretic patterns indicated different LPS structures for these bacteria. The immunomodulatory lipid A was isolated after mild acetic acid hydrolysis. The electrospray ionization ion-trap mass spectra revealed monophosphorylated molecules corresponding to tetra- and pentaacylated structures with common structural features between the two strains. Despite peculiar structural characteristics, none of these two LPS influenced the expression of the macrophage-expressed gene S. domuncula unlike the Escherichia coli ones. Further research will have to include a larger number of genes to understand how this animal can distinguish between LPS with resembling structures and discriminate between bacteria associated with it. PMID- 26262626 TI - Metabolomic Analysis of Blood Plasma after Oral Administration of N-acetyl-d Glucosamine in Dogs. AB - N-acetyl-d-glucosamine (GlcNAc) is a monosaccharide that polymerizes linearly through (1,4)-beta-linkages. GlcNAc is the monomeric unit of the polymer chitin. GlcNAc is a basic component of hyaluronic acid and keratin sulfate found on the cell surface. The aim of this study was to examine amino acid metabolism after oral GlcNAc administration in dogs. Results showed that plasma levels of ectoine were significantly higher after oral administration of GlcNAc than prior to administration (p < 0.001). To our knowledge, there have been no reports of increased ectoine concentrations in the plasma. The mechanism by which GlcNAc administration leads to increased ectoine plasma concentration remains unclear; future studies are required to clarify this mechanism. PMID- 26262627 TI - Eribulin in Cancer Treatment. AB - Halichondrin B is a complex, natural, polyether macrolide derived from marine sponges. Eribulin is a structurally-simplified, synthetic, macrocyclic ketone analogue of Halichondrin B. Eribulin was approved by United States Food and Drug Administration in 2010 as a third-line therapy for metastatic breast cancer patients who have previously been treated with an anthracycline and a taxane. It has a unique microtubule dynamics inhibitory action. Phase III studies have either been completed or are currently ongoing in breast cancer, soft tissue sarcoma, and non-small cell lung cancer. Phase I and II studies in multiple cancers and various combinations are currently ongoing. This article reviews the available information on eribulin with respect to its clinical pharmacology, pharmacokinetics, pharmacodynamics, mechanism of action, metabolism, preclinical studies, and with special focus on clinical trials. PMID- 26262629 TI - Additional Burden of Diseases Associated with Cadmium Exposure: A Case Study of Cadmium Contaminated Rice Fields in Mae Sot District, Tak Province, Thailand. AB - The cadmium (Cd) contaminated rice fields in Mae Sot District, Tak Province, Thailand has been one of the major environmental problems in Thailand for the last 10 years. We used disability adjusted life years (DALYs) to estimate the burden of disease attributable to Cd in terms of additional DALYs of Mae Sot residents. Cd exposure data included Cd and beta2-microglobulin (beta2-MG) in urine (as an internal exposure dose) and estimated cadmium daily intake (as an external exposure dose). Compared to the general Thai population, Mae Sot residents gained 10%-86% DALYs from nephrosis/nephritis, heart diseases, osteoporosis and cancer depending on their Cd exposure type and exposure level. The results for urinary Cd and dietary Cd intake varied according to the studies used for risk estimation. The ceiling effect was observed in results using dietary Cd intake because of the high Cd content in rice grown in the Mae Sot area. The results from beta2-MG were more robust with additional DALYs ranging from 36%-86% for heart failure, cerebral infraction, and nephrosis/nephritis. Additional DALYs is a useful approach for assessing the magnitude of environmental Cd exposure. The Mae Sot population lost more healthy life compared to populations living in a non- or less Cd polluted area. This method should be applicable to various types of environmental contamination problems if exposure assessment information is available. PMID- 26262628 TI - Porifera Lectins: Diversity, Physiological Roles and Biotechnological Potential. AB - An overview on the diversity of 39 lectins from the phylum Porifera is presented, including 38 lectins, which were identified from the class of demosponges, and one lectin from the class of hexactinellida. Their purification from crude extracts was mainly performed by using affinity chromatography and gel filtration techniques. Other protocols were also developed in order to collect and study sponge lectins, including screening of sponge genomes and expression in heterologous bacterial systems. The characterization of the lectins was performed by Edman degradation or mass spectrometry. Regarding their physiological roles, sponge lectins showed to be involved in morphogenesis and cell interaction, biomineralization and spiculogenesis, as well as host defense mechanisms and potentially in the association between the sponge and its microorganisms. In addition, these lectins exhibited a broad range of bioactivities, including modulation of inflammatory response, antimicrobial and cytotoxic activities, as well as anticancer and neuromodulatory activity. In view of their potential pharmacological applications, sponge lectins constitute promising molecules of biotechnological interest. PMID- 26262630 TI - Testis-Specific Lactate Dehydrogenase (LDH-C4) in Skeletal Muscle Enhances a Pika's Sprint-Running Capacity in Hypoxic Environment. AB - LDH-C4 is a lactate dehydrogenase that catalyzes the conversion of pyruvate to lactate. In mammals, ldh-c was originally thought to be expressed only in testis and spermatozoa. Plateau pika (Ochotona curzoniae), which belongs to the genus Ochotona of the Ochotonidea family, is a hypoxia tolerant mammal living 3000-5000 m above sea level on the Qinghai-Tibet Plateau, an environment which is strongly hypoxic. Ldh-c is expressed not only in testis and sperm but also in somatic tissues of plateau pika. In this study, the effects of N-propyl oxamate and N isopropyl oxamate on LDH isozyme kinetics were compared to screens for a selective inhibitor of LDH-C4. To reveal the role and physiological mechanism of LDH-C4 in skeletal muscle of plateau pika, we investigated the effect of N isopropyl oxamate on the pika exercise tolerance as well as the physiological mechanism. Our results show that Ki of N-propyl oxamate and N-isopropyl oxamate for LDH-A4, LDH-B4, and LDH-C4 were 0.094 mmol/L and 0.462 mmol/L, 0.119 mmol/L and 0.248 mmol/L, and 0.015 mmol/L and 0.013 mmol/L, respectively. N-isopropyl oxamate is a powerful selective inhibitor of plateau pika LDH-C4. In our exercise tolerance experiment, groups treated with inhibitors had significantly lower swimming times than the uninhibited control group. The inhibition rates of LDH, LD, and ATP were 37.12%, 66.27%, and 32.42%, respectively. Our results suggested that ldh-c is expressed in the skeletal muscle of plateau pika, and at least 32.42% of ATP in the skeletal muscle is catalyzed by LDH-C4 by anaerobic glycolysis. This suggests that pika has reduced dependence on oxygen and enhanced adaptation to hypoxic environment due to increased anaerobic glycolysis by LDH-C4 in skeletal muscle. LDH-C4 in plateau pika plays the crucial role in anaerobic glycolysis and generates ATP rapidly since this is the role of LDH-A4 in most species on plain land, which provide evidence that the native humans and animals in Qinghai-Tibet plateau can adapt to the hypoxia environment. PMID- 26262631 TI - Doctor-Shopping Behaviors among Traditional Chinese Medicine Users in Taiwan. AB - Doctor-shopping has caused an increase in medical expense, potential to receive duplicate medications, and suffer adverse drug reactions. We carried out a population-based retrospective study aimed at examining the user patterns of traditional Chinese medicine (TCM) ambulatory care in Taiwan. We retrieved complete TCM ambulatory visit datasets for the year 2007 from the National Health Insurance database in Taiwan. We defined the patients whose distribution of TCM physician numbers scored more than 97.5 percent (more than, or equal to, five TCM physicians) within one year as TCM doctor-shoppers. In total, 6,596,814 subjects (28.9%) paid TCM visits during that year. All 177,728 subjects (2.69%) who visited more than five (including) TCM physicians were classified as TCM shoppers. The most prevalent diagnostic grouping was upper respiratory infections (44.7%) and sprains and strains (44.0%). Men had a lower odds ratio (OR) among TCM shoppers than women (OR = 0.94, 95% confidence interval (CI) = 0.93-0.96). Younger people were less likely to be TCM shoppers than other people were. The ORs of TCM shoppers were higher among veterans and low-income patients (OR = 1.29 (1.23-1.35), and 1.33 (1.27-1.41)). In conclusion, health education on the potential of drug interactions and iatrogenic health risks incurred from doctor shopping should be addressed to those high-risk patients. PMID- 26262632 TI - Variability and Stability in Daily Moderate-to-Vigorous Physical Activity among 10 Year Old Children. AB - Day-to-day variability and stability of children's physical activity levels across days of the week are not well understood. Our aims were to examine the day to-day variability of moderate-to-vigorous physical activity (MVPA), to determine factors influencing the day-to-day variability of MVPA and to estimate stability of MVPA in children. The sample comprises 686 Portuguese children (10 years of age). MVPA was assessed with an accelerometer, and BMI was computed from measured height and weight. Daily changes in MVPA and their correlates (gender, BMI, and maturity) were modeled with a multilevel approach, and tracking was calculated using Foulkes & Davies gamma. A total of 51.3% of boys and 26.2% of girls achieved 60 min/day of MVPA on average. Daily MVPA was lower during the weekend (23.6% of boys and 13.6% of girls comply with the recommended 60 min/day of MVPA) compared to weekdays (60.8% and 35.4%, boys and girls, respectively). Normal weight children were more active than obese children and no effect was found for biological maturation. Tracking is low in both boys (gamma = 0.59 +/- 0.01) and girls (gamma = 0.56 +/- 0.01). Children's MVPA levels during a week are highly unstable. In summary, boys are more active than girls, maturation does not affect their MVPA, and obese children are less likely to meet 60 min/day of MVPA. These results highlight the importance of providing opportunities for increasing children's daily MVPA on all days of week, especially on the weekend. PMID- 26262633 TI - Wrist Hypothermia Related to Continuous Work with a Computer Mouse: A Digital Infrared Imaging Pilot Study. AB - Computer work is characterized by sedentary static workload with low-intensity energy metabolism. The aim of our study was to evaluate the dynamics of skin surface temperature in the hand during prolonged computer mouse work under different ergonomic setups. Digital infrared imaging of the right forearm and wrist was performed during three hours of continuous computer work (measured at the start and every 15 minutes thereafter) in a laboratory with controlled ambient conditions. Four people participated in the study. Three different ergonomic computer mouse setups were tested on three different days (horizontal computer mouse without mouse pad; horizontal computer mouse with mouse pad and padded wrist support; vertical computer mouse without mouse pad). The study revealed a significantly strong negative correlation between the temperature of the dorsal surface of the wrist and time spent working with a computer mouse. Hand skin temperature decreased markedly after one hour of continuous computer mouse work. Vertical computer mouse work preserved more stable and higher temperatures of the wrist (>30 degrees C), while continuous use of a horizontal mouse for more than two hours caused an extremely low temperature (<28 degrees C) in distal parts of the hand. The preliminary observational findings indicate the significant effect of the duration and ergonomics of computer mouse work on the development of hand hypothermia. PMID- 26262634 TI - Titanium Dioxide Nanoparticle Penetration into the Skin and Effects on HaCaT Cells. AB - Titanium dioxide nanoparticles (TiO2NPs) suspensions (concentration 1.0 g/L) in synthetic sweat solution were applied on Franz cells for 24 h using intact and needle-abraded human skin. Titanium content into skin and receiving phases was determined. Cytotoxicity (MTT, AlamarBlue((r)) and propidium iodide, PI, uptake assays) was evaluated on HaCat keratinocytes after 24 h, 48 h, and seven days of exposure. After 24 h of exposure, no titanium was detectable in receiving solutions for both intact and damaged skin. Titanium was found in the epidermal layer after 24 h of exposure (0.47 +/- 0.33 MUg/cm(2)) while in the dermal layer, the concentration was below the limit of detection. Damaged skin, in its whole, has shown a similar concentration (0.53 +/- 0.26 MUg/cm(2)). Cytotoxicity studies on HaCaT cells demonstrated that TiO2NPs induced cytotoxic effects only at very high concentrations, reducing cell viability after seven days of exposure with EC50s of 8.8 * 10(-4) M (MTT assay), 3.8 * 10(-5) M (AlamarBlue((r)) assay), and 7.6 * 10(-4) M (PI uptake, index of a necrotic cell death). Our study demonstrated that TiO2NPs cannot permeate intact and damaged skin and can be found only in the stratum corneum and epidermis. Moreover, the low cytotoxic effect observed on human HaCaT keratinocytes suggests that these nano-compounds have a potential toxic effect at the skin level only after long-term exposure. PMID- 26262635 TI - Altered Expression of Genes in Signaling Pathways Regulating Proliferation of Hematopoietic Stem and Progenitor Cells in Mice with Subchronic Benzene Exposure. AB - Leukemias and hematopoietic disorders induced by benzene may arise from the toxicity of benzene to hematopoietic stem or progenitor cells (HS/PCs). Since there is a latency period between initial benzene exposure and the development of leukemia, subsequent impact of benzene on HS/PCs are crucial for a deeper understanding of the carcinogenicity and hematotoxicity in post-exposure stage. This study aims to explore the effects of benzene on HS/PCs and gene-expression in Wnt, Notch and Hh signaling pathways in post-exposure stage. The C3H/He mice were injected subcutaneously with benzene (0, 150, 300 mg/kg/day) for three months and were monitored for another 10 months post-exposure. The body weights were monitored, the relative organ weights, blood parameters and bone marrow smears were examined. Frequency of lineage(-) sca-1(+) c-kit(+) (LSK) cells, capability of colony forming and expression of genes in Wnt, Notch and Hedghog (Hh) signaling pathways were also analyzed. The colony formation of the progenitor cells for BFU-E, CFU-GEMM and CFU-GM was significantly decreased with increasing benzene exposure relative to controls, while no significant difference was observed in colonies for CFU-G and CFU-M. The mRNA level of cyclin D1 was increased and Notch 1 and p53 were decreased in LSK cells in mice exposed to benzene but with no statistical significance. These results suggest that subsequent toxic effects of benzene on LSK cells and gene expression in Wnt, Notch and Hh signaling pathways persist in post-exposure stage and may play roles in benzene-induced hematotoxicity. PMID- 26262636 TI - Characterization and Feasibility Assessment of Recycled Paper Mill Sludges for Land Application in Relation to the Environment. AB - The disposal of industrial paper mill sludge waste is a big issue and has a great importance all over the world. A study was conducted to determine the chemical properties of recycled paper mill sludge (RPMS) and assess its possibilities for land application. RPMS samples were collected from six different paper mills in Malaysia and analyzed for physical and chemical properties, heavy metals, polycyclic aromatic hydrocarbons, (13)C-NMR spectra and for the presence of dioxins/furans. The RPMS was dewatered, sticky with a strong odour, an average moisture of 65.08%, pH 7.09, cation exchange capacity (CEC) 14.43 cmol (+) kg( 1), N 1.45, P 0.18, K 0.12, Ca 0.82, Mg 0.73, Na 0.76 and Al, 1.38%. The polycyclic aromatic hydrocarbons (PAHs) and heavy metals levels were below the standard Class 2 limits. The dioxin and furan were in below the standard concentration of Class 1. The most prominent peak in the (13)C-NMR spectra of RPMS was centered at 31 ppm, proving the presence of methylene (-CH2) groups in long aliphatic chains, with lipids and proteins. The signal at 89 ppm and highly shielded shoulder at 83 ppm were due to presence of cellulose carbon C-4, and the peak at 63 and 65 ppm was due to the cellulose carbon spectrum. The RPMS therefore contains significant amount of nutrients with safe levels of heavy metals and PAHs for environment and can be used as a fertilizer and soil amendment for land application. PMID- 26262637 TI - Genetic Characterization of the Belgian Nephropathogenic Infectious Bronchitis Virus (NIBV) Reference Strain B1648. AB - The virulent nephropathogenic infectious bronchitis virus (NIBV) strain B1648 was first isolated in 1984, in Flanders, Belgium. Despite intensive vaccination, B1648 and its variants are still circulating in Europe and North Africa. Here, the full-length genome of this Belgian NIBV reference strain was determined by next generation sequencing (NGS) to understand its evolutionary relationship with other IBV strains, and to identify possible genetic factors that may be associated with the nephropathogenicity. Thirteen open reading frames (ORFs) were predicted in the B1648 strain (51UTR-1a-1b-S-3a-3b-E-M-4b-4c-5a-5b-N-6b-31UTR). ORFs 4b, 4c and 6b, which have been rarely reported in literature, were present in B1648 and most of the other IBV complete genomes. According to phylogenetic analysis of the full-length genome, replicase transcriptase complex, spike protein, partial S1 gene and M protein, B1648 strain clustered with the non Massachusetts type strains NGA/A116E7/2006, UKr 27-11, QX-like ITA/90254/2005, QX like CK/SWE/0658946/10, TN20/00, RF-27/99, RF/06/2007 and SLO/266/05. Based on the partial S1 fragment, B1648 clustered with the strains TN20/00, RF-27/99, RF/06/2007 and SLO/266/05 and, further designated as B1648 genotype. The full length genome of B1648 shared the highest sequence homology with UKr 27-11, Gray, JMK, and NGA/A116E7/2006 (91.2% to 91.6%) and was least related with the reference Beaudette and Massachusetts strains (89.7%). Nucleotide and amino acid sequence analyses indicated that B1648 strain may have played an important role in the evolution of IBV in Europe and North Africa. Further, the nephropathogenicity determinants might be located on the 1a, spike, M and accessory proteins (3a, 3b, 4b, 4c, 5a, 5b and 6b). Overall, strain B1648 is distinct from all the strains reported so far in Europe and other parts of the world. PMID- 26262639 TI - Contribution of Epigenetic Modifications to the Decline in Transgene Expression from Plasmid DNA in Mouse Liver. AB - Short-term expression of transgenes is one of the problems frequently associated with non-viral in vivo gene transfer. To obtain experimental evidence for the design of sustainable transgene expression systems, the contribution of epigenetic modifications to the decline in transgene expression needs to be investigated. Bisulfite sequencing and reactivation by hydrodynamic injection of isotonic solution were employed to investigate methylation statues of CpG in transiently expressing plasmid, pCMV-Luc, in mouse liver after hydrodynamic delivery. The cytosines of CpGs in the promoter region of pCMV-Luc were methylated in mouse liver, but the methylation was much later than the decline in the expression. The expression from pre-methylated pCMV-Luc was insensitive to reactivation. Neither an inhibitor of DNA methylation nor an inhibitor of histone deacetylation had significant effects on transgene expression after hydrodynamic injection of pCMV-Luc. Partial hepatectomy, which reduces the transgene expression from the non-integrated vector into the genome, significantly reduced the transgene expression of human interferon gamma from a long-term expressing plasmid pCpG-Hugamma, suggesting that the CpG-reduced plasmid was not significantly integrated into the genomic DNA. These results indicate that the CpG-reduced plasmids achieve prolonged transgene expression without integration into the host genome, although the methylation status of CpG sequences in plasmids will not be associated with the prolonged expression. PMID- 26262638 TI - Mate-Pair Sequencing as a Powerful Clinical Tool for the Characterization of Cancers with a DNA Viral Etiology. AB - DNA viruses are known to be associated with a variety of different cancers. Human papillomaviruses (HPV) are a family of viruses and several of its sub-types are classified as high-risk HPVs as they are found to be associated with the development of a number of different cancers. Almost all cervical cancers appear to be driven by HPV infection and HPV is also found in most cancers of the anus and at least half the cancers of the vulva, penis and vagina, and increasingly found in one sub-type of head and neck cancers namely oropharyngeal squamous cell carcinoma. Our understanding of HPVs role in cancer development comes from extensive studies done on cervical cancer and it has just been assumed that HPV plays an identical role in the development of all other cancers arising in the presence of HPV sequences, although this has not been proven. Most invasive cervical cancers have the HPV genome integrated into one or more sites within the human genome. One powerful tool to examine all the sites of HPV integration in a cancer but that also provides a comprehensive view of genomic alterations in that cancer is the use of next generation sequencing of mate-pair libraries produced from the DNA isolated. We will describe how this powerful technology can provide important information about the genomic organization within an individual cancer genome, and how this has demonstrated that HPVs role in oropharyngeal squamous cell carcinoma is distinct from that in cervical cancer. We will also describe why the sequencing of mate-pair libraries could be a powerful clinical tool for the management of patients with a DNA viral etiology and how this could quickly transform the care of these patients. PMID- 26262640 TI - Proanthocyanidins Prevent High Glucose-Induced Eye Malformation by Restoring Pax6 Expression in Chick Embryo. AB - Gestational diabetes mellitus (GDM) is one of the leading causes of offspring malformations, in which eye malformation is an important disease. It has raised demand for therapy to improve fetal outcomes. In this study, we used chick embryo to establish a GDM model to study the protective effects of proanthocyanidins on eye development. Chick embryos were exposed to high glucose (0.2 mmol/egg) on embryo development day (EDD) 1. Proanthocyanidins (1 and 10 nmol/egg) were injected into the air sac on EDD 0. Results showed that both dosages of proanthocyanidins could prevent the eye malformation and rescue the high glucose induced oxidative stress significantly, which the similar effects were showed in edaravone. However, proanthocyanidins could not decrease the glucose concentration of embryo eye. Moreover, the key genes regulating eye development, Pax6, was down-regulated by high glucose. Proanthocyanidins could restore the suppressed expression of Pax6. These results indicated proanthocyanidins might be a promising natural agent to prevent high glucose-induced eye malformation by restoring Pax6 expression. PMID- 26262641 TI - Dietary Patterns, Alcohol Consumption and Risk of Coronary Heart Disease in Adults: A Meta-Analysis. AB - Previous studies reported the potential associations between dietary patterns and the risk of coronary heart disease (CHD) in adulthood, however a consistent perspective has not been established to date. Herein, we carried out this meta analysis to evaluate the associations between dietary patterns and the risk of CHD. MEDLINE and EBSCO were searched for relevant articles published up to April 2015. A total of 35 articles (reporting 37 original studies) met the inclusion criteria and were included in the present meta-analysis. The decreased risk of CHD was shown for the highest compared with the lowest categories of healthy/prudent dietary patterns (odds ratio (OR) = 0.67; 95% confidence interval (CI): 0.60, 0.75; p < 0.00001) and alcohol consumption (OR = 0.68; 95% CI: 0.59, 0.78; p < 0.00001). There was evidence of an increased risk of CHD in the highest compared with the lowest categories of the unhealthy/Western-type dietary patterns (OR = 1.45; 95% CI: 1.05, 2.01; p = 0.02). The results of this meta analysis indicate that different dietary patterns may be associated with the risk of CHD. PMID- 26262642 TI - The Long Term Impact of Micronutrient Supplementation during Infancy on Cognition and Executive Function Performance in Pre-School Children. AB - Brain growth and development are critically dependent on several micronutrients. During early development cellular activity may be sensitive to micronutrient deficiencies, however the evidence from human studies is equivocal. The objective of this study was to examine the long-term cognitive and social-emotional effects of multiple micronutrient supplementation compared with iron supplementation alone, administered during infancy. This study was a follow-up to an initial randomized, double-blind controlled trial (RCT) in 2010 in which 902 infants, aged 6-17 months, from Lima, Peru, were given daily supplements of either iron (Fe) or multiple micronutrients (MMN) including zinc (451 in each group). The supplementation period for both groups was six months. In 2012, a subsample of 184 children from the original cohort (now aged 36-48 months) was randomly selected to participate in a follow-up trial and was assessed for intelligence, working memory, inhibition, and executive function. The tests showed no significant differences between the supplementation groups though there were some gender differences, with girls displaying higher scores than boys across both groups on the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) Verbal IQ sentences subtest, the Day-Night cognitive test and on the Brief Infant Toddler Social Emotional Assessment (BITSEA) social competency, and boys scoring higher than girls in problem behaviour. The results indicate that MMN supplementation had no long term additional effects on cognitive function compared with iron supplementation alone. The timing of supplement administration for maximum impact on a child's cognitive development requires further investigation. PMID- 26262643 TI - Nuclear Import of Yeast Proteasomes. AB - Proteasomes are highly conserved protease complexes responsible for the degradation of aberrant and short-lived proteins. In highly proliferating yeast and mammalian cells, proteasomes are predominantly nuclear. During quiescence and cell cycle arrest, proteasomes accumulate in granules in close proximity to the nuclear envelope/ER. With prolonged quiescence in yeast, these proteasome granules pinch off as membraneless organelles, and migrate as stable entities through the cytoplasm. Upon exit from quiescence, the proteasome granules clear and the proteasomes are rapidly transported into the nucleus, a process reflecting the dynamic nature of these multisubunit complexes. Due to the scarcity of studies on the nuclear transport of mammalian proteasomes, we summarised the current knowledge on the nuclear import of yeast proteasomes. This pathway uses canonical nuclear localisation signals within proteasomal subunits and Srp1/Kap95, and the canonical import receptor, named importin/karyopherin alphabeta. Blm10, a conserved 240 kDa protein, which is structurally related to Kap95, provides an alternative import pathway. Two models exist upon which either inactive precursor complexes or active holo-enzymes serve as the import cargo. Here, we reconcile both models and suggest that the import of inactive precursor complexes predominates in dividing cells, while the import of mature enzymes mainly occurs upon exit from quiescence. PMID- 26262644 TI - Chromatin Dynamics in Vivo: A Game of Musical Chairs. AB - Histones are a major component of chromatin, the nucleoprotein complex fundamental to regulating transcription, facilitating cell division, and maintaining genome integrity in almost all eukaryotes. In addition to canonical, replication-dependent histones, replication-independent histone variants exist in most eukaryotes. In recent years, steady progress has been made in understanding how histone variants assemble, their involvement in development, mitosis, transcription, and genome repair. In this review, we will focus on the localization of the major histone variants H3.3, CENP-A, H2A.Z, and macroH2A, as well as how these variants have evolved, their structural differences, and their functional significance in vivo. PMID- 26262646 TI - Grafts for Ridge Preservation. AB - Alveolar ridge bone resorption is a biologic phenomenon that occurs following tooth extraction and cannot be prevented. This paper reviews the vertical and horizontal ridge dimensional changes that are associated with tooth extraction. It also provides an overview of the advantages of ridge preservation as well as grafting materials. A Medline search among English language papers was performed in March 2015 using alveolar ridge preservation, ridge augmentation, and various graft types as search terms. Additional papers were considered following the preliminary review of the initial search that were relevant to alveolar ridge preservation. The literature suggests that ridge preservation methods and augmentation techniques are available to minimize and restore available bone. Numerous grafting materials, such as autografts, allografts, xenografts, and alloplasts, currently are used for ridge preservation. Other materials, such as growth factors, also can be used to enhance biologic outcome. PMID- 26262648 TI - Low-Temperature and Solution-Processed Amorphous WO(x) as Electron-Selective Layer for Perovskite Solar Cells. AB - The electron-selective layer (ESL) is an indispensable component of perovskite solar cells (PSCs) and is responsible for the collection of photogenerated electrons. Preparing ESL at a low temperature is significant for future fabrication of flexible PSCs. In this work, solution-processed amorphous WO(x) thin film was prepared facilely at low temperature and used as ESL in PSCs. Results indicated that a large quantity of nanocaves were observed in the WO(x) thin film. In comparison with the conventional TiO2 ESL, the WO(x) ESL exhibited comparable light transmittance but higher electrical conductivity. Compared with the TiO2-based PSCs, PSCs that use WO(x) ESL exhibited comparable photoelectric conversion efficiency, larger short-circuit current density, but lower open circuit voltage. Electrochemical characterization indicated that the unsatisfied open-circuit voltage and fill factor were caused by the inherent charge recombination. This study demonstrated that this material is an excellent candidate for ESL. PMID- 26262647 TI - The Detection of Helicobacter hepaticus Using Whispering-Gallery Mode Microcavity Optical Sensors. AB - Current bacterial detection techniques are relatively slow, require bulky instrumentation, and usually require some form of specialized training. The gold standard for bacterial detection is culture testing, which can take several days to receive a viable result. Therefore, simpler detection techniques that are both fast and sensitive could greatly improve bacterial detection and identification. Here, we present a new method for the detection of the bacteria Helicobacter hepaticus using whispering-gallery mode (WGM) optical microcavity-based sensors. Due to minimal reflection losses and low material adsorption, WGM-based sensors have ultra-high quality factors, resulting in high-sensitivity sensor devices. In this study, we have shown that bacteria can be non-specifically detected using WGM optical microcavity-based sensors. The minimum detection for the device was 1 * 10(4) cells/mL, and the minimum time of detection was found to be 750 s. Given that a cell density as low as 1 * 10(3) cells/mL for Helicobacter hepaticus can cause infection, the limit of detection shown here would be useful for most levels where Helicobacter hepaticus is biologically relevant. This study suggests a new approach for H. hepaticus detection using label-free optical sensors that is faster than, and potentially as sensitive as, standard techniques. PMID- 26262649 TI - pH Oscillator Stretched in Space but Frozen in Time. AB - Chemical oscillations are studied using a continuous-flow microfluidic system transforming the time domain of chemical oscillators into a spatial domain. This system allows one (i) to monitor the dynamics of chemical oscillators with the accuracy of vigorously stirred batch reactors but with the ease and speed of CSTRs and (ii) to rapidly screen the phase space of chemical oscillators in just one experiment versus a traditional series of batch measurements. PMID- 26262650 TI - Ultralow Absorption Coefficient and Temperature Dependence of Radiative Recombination of CH3NH3PbI3 Perovskite from Photoluminescence. AB - Spectrally resolved photoluminescence is used to measure the band-to-band absorption coefficient alpha(BB)(homega) of organic-inorganic hybrid perovskite methylammonium lead iodide (CH3NH3PbI3) films from 675 to 1400 nm. Unlike other methods used to extract the absorption coefficient, photoluminescence is only affected by band-to-band absorption and is capable of detecting absorption events at very low energy levels. Absorption coefficients as low as 10-14 cm-1 are detected at room temperature for long wavelengths, which is 14 orders of magnitude lower than reported values at shorter wavelengths. The temperature dependence of alpha(BB)(homega) is calculated from the photoluminescence spectra of CH3NH3PbI3 in the temperature range 80-360 K. Based on the temperature dependent alpha(BB)(homega), the product of the radiative recombination coefficient and square of the intrinsic carrier density, B(T) * n(i)2, is also obtained. PMID- 26262651 TI - In Situ Thermal Decomposition of Exfoliated Two-Dimensional Black Phosphorus. AB - With a semiconducting band gap and high charge carrier mobility, two-dimensional (2D) black phosphorus (BP)-often referred to as phosphorene-holds significant promise for next generation electronics and optoelectronics. However, as a 2D material, it possesses a higher surface area to volume ratio than bulk BP, suggesting that its chemical and thermal stability will be modified. Herein, an atomic-scale microscopic and spectroscopic study is performed to characterize the thermal degradation of mechanically exfoliated 2D BP. From in situ scanning/transmission electron microscopy, decomposition of 2D BP is observed to occur at ~400 degrees C in vacuum, in contrast to the 550 degrees C bulk BP sublimation temperature. This decomposition initiates via eye-shaped cracks along the [001] direction and then continues until only a thin, amorphous red phosphorus like skeleton remains. In situ electron energy loss spectroscopy, energy-dispersive X-ray spectroscopy, and energy-loss near-edge structure changes provide quantitative insight into this chemical transformation process. PMID- 26262652 TI - Kinetic Evidence of Two Pathways for Charge Recombination in NiO-Based Dye Sensitized Solar Cells. AB - Mesoporous nickel oxide has been used as electrode material for p-type dye sensitized solar cells (DSCs) for many years but no high efficiency cells have yet been obtained. One of the main issues that lowers the efficiency is the poor fill factor, for which a clear reason is still missing. In this paper we present the first evidence for a relation between applied potential and the charge recombination rate of the NiO electrode. In particular, we find biphasic recombination kinetics: a fast (15 ns) pathway attributed to the reaction with the holes in the valence band and a slow (1 ms) pathway assigned to the holes in the trap states. The fast component is the most relevant at positive potentials, while the slow component becomes more important at negative potentials. This means that at the working condition of the cell, the fast recombination is the most important. This could explain the low fill factor of NiO-based DSCs. PMID- 26262653 TI - Specific Binding of Cholesterol to the Amyloid Precursor Protein: Structure of the Complex and Driving Forces Characterized in Molecular Detail. AB - C99 is the C-terminal membrane-bound fragment of the amyloid precursor protein that is cleaved by gamma-secretase to release Abeta peptides, the hallmark of Alzheimer's disease (AD). Specific interactions of C99 with cholesterol have been proposed to underlie the recognized role of cholesterol in promoting amyloidogenesis. By using molecular dynamics simulations, we studied cholesterol binding to C99 in a lipid bilayer. We determined the free-energy profile of binding and analyzed the structure of C99/cholesterol complexes in two low-energy binding modes. We also examined the complexation driving forces and found, unexpectedly, that the interactions between the GxxxG dimerization motif and the cholesterol ring system are not sufficient for binding and that further stabilization mediated by the C99 N-terminal domain is essential. Taken together, our results strongly support the view that C99 specifically binds cholesterol in the cell membrane; the detailed information on the structure and energetics of the complex may assist in the design of new anti-AD drugs. PMID- 26262654 TI - Molecular-structure Control of Ultrafast Electron Injection at Cationic Porphyrin CdTe Quantum Dot Interfaces. AB - Charge transfer (CT) at donor (D)/acceptor (A) interfaces is central to the functioning of photovoltaic and light-emitting devices. Understanding and controlling this process on the molecular level has been proven to be crucial for optimizing the performance of many energy-challenge relevant devices. Here, we report the experimental observations of controlled on/off ultrafast electron transfer (ET) at cationic porphyrin-CdTe quantum dot (QD) interfaces using femto- and nanosecond broad-band transient absorption (TA) spectroscopy. The time resolved data demonstrate how one can turn on/off the electron injection from porphyrin to the CdTe QDs. With careful control of the molecular structure, we are able to tune the electron injection at the porphyrin-CdTe QD interface from zero to very efficient and ultrafast. In addition, our data demonstrate that the ET process occurs within our temporal resolution of 120 fs, which is one of the fastest times recorded for organic photovoltaics. PMID- 26262655 TI - Capping Ligand-Induced Self-Assembly for Quantum Dot Sensitized Solar Cells. AB - Quantum dot-sensitized solar cells (QDSCs), having the advantages of low-cost assembling process, economically viable materials and intrinsic optoelectronic properties of QD sensitizers, are regarded as attractive candidates for the third generation solar cells. In spite of the previous unsatisfied performance resulted from poor sensitization, an increasing power conversion efficiency has been experimentally confirmed with the development of effective deposition approaches in the last five years. In this Perspective article, we present an overview on versatile QD deposition methods, regarding mainly the effective loading of QDs and surface chemistry issues. Linker-assisted assembly, a most efficient sensitizer deposition approach to achieve fast, uniform and dense coverage of the sensitizers on mesoporous TiO2 film electrode, will be discussed with emphasis. Recent advances based on this deposition technique in achieving high efficiency are presented. Also, combined efforts regarding the overall improvement of the device have been discussed to provide more possible access to higher power conversion efficiencies of the QDSCs. PMID- 26262656 TI - Surface-Altered Protonation Studied by Photoelectron Spectroscopy and Reactive Dynamics Simulations. AB - The extent to which functional groups are protonated at aqueous interfaces as compared to bulk is deemed essential to several areas in chemistry and biology. The origin of such changes has been the source of intense debate. We use X-ray photoelectron spectroscopy and all-atom reactive molecular dynamics simulations as two independent methods to probe, at the molecular scale, both bulk and surface distributions of protonated species of cysteine in an aqueous solution. We show that the distribution of the cysteine species at the surface is quite different from that in the bulk. We argue that this finding, however, cannot be simply related to a change in the extent of proton sharing between the two conjugate acid/base pairs that may occur between these two regions. The present theoretical simulations identify species at the surface that are not present in the bulk. PMID- 26262657 TI - Understanding DABCO Nanorotor Dynamics in Isostructural Metal-Organic Frameworks. AB - Flexible framework dynamics present in the subset of metal-organic frameworks known as soft porous crystals give rise to interesting structural properties that are unique to this class of materials. In this work, we use experiments and molecular simulation to understand the highly dynamic nanorotor behavior of the 1,4-diazabicyclo[2.2.2]octane (DABCO) ligand in the pillared Zn-DMOF and Zn-DMOF TM (TM = tetramethyl) structures. While DABCO is known to be displaced in the presence of water in the parent Zn-DMOF structure, the Zn-DMOF-TM variation is highly stable even after adsorbing significant amounts of water vapor. The dynamics of DABCO in the presence of water guest molecules is therefore also explored in the Zn-DMOF-TM structure via in situ NMR and IR experiments. This analysis shows that the rotational motion of the DABCO linkers is dependent on water content, but not a likely source of water instability because the dynamics are fast and largely unaffected by the presence of methyl functional groups. PMID- 26262659 TI - Coherent Control of Photofragment Distributions Using Laser Phase Modulation in the Weak-Field Limit. AB - The possibility of quantum interference control of the final state distributions of photodissociation fragments by means of pure phase modulation of the pump laser pulse in the weak-field regime is demonstrated theoretically for the first time. The specific application involves realistic wave packet calculations of the transient vibrational populations of the Br2(B, v(f)) fragment produced upon predissociation of the Ne-Br2(B) complex, which is excited to a superposition of resonance states using pulses with different linear chirps. Transient phase effects on the fragment populations are found to persist for long times (about 200 ps) after the pulse is over due to interference between overlapping resonances in Ne-Br2(B). PMID- 26262658 TI - VUV Photoelectron Spectroscopy of Cysteine Aqueous Aerosols: A Microscopic View of Its Nucleophilicity at Varying pH Conditions. AB - Cysteine (Cys) is unique due to its highly reactive thiol group. It often regulates the biological function of proteins by acting as the redox site. Despite its biological significance, however, the valence electronic structure of Cys under the aqueous environments remains unavailable. Here, we report the VUV photoelectron spectroscopy of Cys aqueous aerosols via a newly built aerosol VUV photoelectron spectroscopy apparatus. The photoelectron spectra of Cys show distinct band shapes at varying pH conditions, reflecting the altered molecular orbital characters when its dominating form changes. The ionization energy of Cys is determined to be 8.98 +/- 0.05 eV at low pH. A new feature at a binding energy of 6.97 +/- 0.05 eV is observed at high pH, suggesting that the negative charge on the thiolate group becomes the first electron to be removed upon ionization. This work implies that when Cys is involved in redox processes, the charge transfer mechanism may be entirely altered under different pH conditions. PMID- 26262660 TI - Prospects and Limits of Energy Storage in Batteries. AB - Energy densities of Li ion batteries, limited by the capacities of cathode materials, must increase by a factor of 2 or more to give all-electric automobiles a 300 mile driving range on a single charge. Battery chemical couples with very low equivalent weights have to be sought to produce such batteries. Advanced Li ion batteries may not be able to meet this challenge in the near term. The state-of-the-art of Li ion batteries is discussed, and the challenges of developing ultrahigh energy density rechargeable batteries are identified. Examples of ultrahigh energy density battery chemical couples include Li/O2, Li/S, Li/metal halide, and Li/metal oxide systems. Future efforts are also expected to involve all-solid-state batteries with performance similar to their liquid electrolyte counterparts, biodegradable batteries to address environmental challenges, and low-cost long cycle-life batteries for large-scale energy storage. Ultimately, energy densities of electrochemical energy storage systems are limited by chemistry constraints. PMID- 26262645 TI - Calcium Orthophosphate-Containing Biocomposites and Hybrid Biomaterials for Biomedical Applications. AB - The state-of-the-art on calcium orthophosphate (CaPO4)-containing biocomposites and hybrid biomaterials suitable for biomedical applications is presented. Since these types of biomaterials offer many significant and exciting possibilities for hard tissue regeneration, this subject belongs to a rapidly expanding area of biomedical research. Through the successful combinations of the desired properties of matrix materials with those of fillers (in such systems, CaPO4 might play either role), innovative bone graft biomaterials can be designed. Various types of CaPO4-based biocomposites and hybrid biomaterials those are either already in use or being investigated for biomedical applications are extensively discussed. Many different formulations in terms of the material constituents, fabrication technologies, structural and bioactive properties, as well as both in vitro and in vivo characteristics have been already proposed. Among the others, the nano-structurally controlled biocomposites, those containing nanodimensional compounds, biomimetically fabricated formulations with collagen, chitin and/or gelatin, as well as various functionally graded structures seem to be the most promising candidates for clinical applications. The specific advantages of using CaPO4-based biocomposites and hybrid biomaterials in the selected applications are highlighted. As the way from a laboratory to a hospital is a long one and the prospective biomedical candidates have to meet many different necessities, the critical issues and scientific challenges that require further research and development are also examined. PMID- 26262661 TI - Modeling the Growth Kinetics of Anodic TiO2 Nanotubes. AB - The fundamental understanding of the barrier layer (delta(b)) growth in TiO2 nanotubes (NTs) is here established and compared with the classical metal oxidation theory from Mott and Cabrera. The role of delta(b) in the anodization of TiO2 NTs under different applied potentials and times was analyzed using scanning transmission electron microscopy (STEM). Contrary to the well-known case of anodic aluminum oxide, we found that delta(b) of TiO2 NTs progressively grows over time due to the nonsteady anodization regime. We then establish a relation between the phenomenological growth of the barrier layer with time and applied voltage, delta(b)(V,t) using the high-field Mott and Cabrera conduction theory. The developed model was found to be in excellent agreement with the experimental data from both STEM and anodization curves. On the basis of these results, the relationship between delta(b) and the anodization time and potential can now be quantitatively understood. PMID- 26262662 TI - Best Practices in Perovskite Solar Cell Efficiency Measurements. Avoiding the Error of Making Bad Cells Look Good. PMID- 26262663 TI - Know the Difference: Scientific Publications versus Scientific Reports. PMID- 26262664 TI - Single-Molecule Identification of Quenched and Unquenched States of LHCII. AB - In photosynthetic light harvesting, absorbed sunlight is converted to electron flow with near-unity quantum efficiency under low light conditions. Under high light conditions, plants avoid damage to their molecular machinery by activating a set of photoprotective mechanisms to harmlessly dissipate excess energy as heat. To investigate these mechanisms, we study the primary antenna complex in green plants, light-harvesting complex II (LHCII), at the single-complex level. We use a single-molecule technique, the Anti-Brownian Electrokinetic trap, which enables simultaneous measurements of fluorescence intensity, lifetime, and spectra in solution. With this approach, including the first measurements of fluorescence lifetime on single LHCII complexes, we access the intrinsic conformational dynamics. In addition to an unquenched state, we identify two partially quenched states of LHCII. Our results suggest that there are at least two distinct quenching sites with different molecular compositions, meaning multiple dissipative pathways in LHCII. Furthermore, one of the quenched conformations significantly increases in relative population under environmental conditions mimicking high light. PMID- 26262665 TI - Boosting the Quantitative Inorganic Surface-Enhanced Raman Scattering Sensing to the Limit: The Case of Nitrite/Nitrate Detection. AB - A high-performance ionic-sensing platform has been developed by an interdisciplinary approach, combining the classical colorimetric Griess reaction and new concepts of nanotechnology, such as plasmonic coupling of nanoparticles and surface-enhanced Raman scattering (SERS) spectroscopy. This approach exploits the advantages of combined SERS/surface-enhanced resonant Raman Scattering (SERRS) by inducing the formation of homogeneous hot spots and a colored complex in resonance with the laser line, to yield detection limits for nitrite down to the subpicomolar level. The performance of this new method was compared with the classical Griess reaction and ionic chromatography showing detection limits about 6 and 3 orders of magnitude lower, respectively. PMID- 26262666 TI - Benefit of Grain Boundaries in Organic-Inorganic Halide Planar Perovskite Solar Cells. AB - The past 2 years have seen the uniquely rapid emergence of a new class of solar cell based on mixed organic-inorganic halide perovskite. Grain boundaries are present in polycrystalline thin film solar cell, and they play an important role that could be benign or detrimental to solar-cell performance. Here we present efficient charge separation and collection at the grain boundaries measured by KPFM and c-AFM in CH3NH3PbI3 film in a CH3NH3PbI3/TiO2/FTO/glass heterojunction structure. We observe the presence of a potential barrier along the grain boundaries under dark conditions and higher photovoltage along the grain boundaries compare to grain interior under the illumination. Also, c-AFM measurement presents higher short-circuit current collection near grain boundaries, confirming the beneficial roles grain boundaries play in collecting carriers efficiently. PMID- 26262667 TI - Lead-Halide Perovskite Solar Cells by CH3NH3I Dripping on PbI2-CH3NH3I-DMSO Precursor Layer for Planar and Porous Structures Using CuSCN Hole-Transporting Material. AB - The sequential fabrication scheme of the CH3NH3PbI3 layer has been improved to fabricate planar-structure CH3NH3PbI3 perovskite solar cells using CuSCN hole transporting material (HTM). In the PbI2 layer fabricated by the spin-coating method, at first, small amounts of CH3NH3I (MAI) and DMSO were incorporated as the first-drip precursor layer on a flat TiO2 layer. On the first-drip precursor layers, an MAI solution was applied by either soaking (MAI-soaking method) or dripping using successive spin coating (MAI-dripping). The morphology and crystal transformations were observed by SEM and XRD, respectively. Using the normal sequential MAI-soaking method, we were unable to fabricate planar CH3NH3PbI3 perovskite solar cells with CuSCN HTM. Using the MAI-dripping method, however, a significant photovoltaic effect has been observed to be planar solar cells. PMID- 26262668 TI - Butterfly-Shaped Diphenylpyrimidine Molecule: Tunable Photophysical Properties by Molecular Self-Assembly Pathways. AB - To understand the relationships between chemical structures, molecular packing structures, and photophysical properties of organic materials, a butterfly shaped diphenylpyrimidine molecule (abbreviated as DPP-6C12) was newly synthesized [Park, M.; Choi, Y.-J.; Kim, D.-Y.; Hwang, S.-H.; Jeong, K.-U. Cryst. Growth Des. 2015, 15, 900-906]. By breaking the molecular symmetry and coplanarity of DPP 6C12, peculiar monotropic phase transitions were observed. Based on two dimensional wide-angle X-ray diffraction and selected area electron diffraction, the molecular packing structures of ordered phases were identified, which were further confirmed by the computer simulations in the real and reciprocal spaces. Finally, we demonstrated that the photophysical properties of DPP-6C12 can be tuned by controlling the molecular packing structures with simple thermal treatments. PMID- 26262669 TI - Reversible Switching of Tb(III) Emission by Sensitization from 2,3 Dihydroxynaphthalene in an Isothermally Reversible Ionic Liquid. AB - A reversible room-temperature ionic liquid (ILO) was prepared by the addition of CO2 to an equimolar mixture of hexylamidine (AD) and butylamine (AN). The ILO and AD/AN mixture were cycled repeatedly by alternating the passage of CO2 and N2 gases through the liquid. The ILO was utilized to sensitize very efficiently energy transfer to and emission by Tb(III) ions when 2,3-dihydroxynaphthalene (DHN) was irradiated. The emission was nearly completely quenched in the AD/AN mixture. The process described here is unique in its use of CO2 and N2 to "switch on and off" the emission by a lanthanide ion, Tb(III) in this case. In the corresponding amidinium dithiocarbamate ionic liquid (ILS), no appreciable Tb(III) emission was found due to quenching of the excited singlet state of DHN by thio groups. The ILS was not reconverted to the AD/AN mixture upon adding N2; N2 bubbling did not result in the displacement of CS2. PMID- 26262670 TI - Perovskite Solar Cells: Beyond Methylammonium Lead Iodide. AB - Organic-inorganic lead halide based perovskites solar cells are by far the highest efficiency solution-processed solar cells, threatening to challenge thin film and polycrystalline silicon ones. Despite the intense research in this area, concerns surrounding the long-term stability as well as the toxicity of lead in the archetypal perovskite, CH3NH3PbI3, have the potential to derail commercialization. Although the search for Pb-free perovskites have naturally shifted to other transition metal cations and formulations that replace the organic moiety, efficiencies with these substitutions are still substantially lower than those of the Pb-perovskite. The perovskite family offers rich multitudes of crystal structures and substituents with the potential to uncover new and exciting photophysical phenomena that hold the promise of higher solar cell efficiencies. In addressing materials beyond CH3NH3PbI3, this Perspective will discuss a broad palette of elemental substitutions, solid solutions, and multidimensional families that will provide the next fillip toward market viability of the perovskite solar cells. PMID- 26262671 TI - Chaotic Soliton Dynamics in Photoexcited trans-Polyacetylene. AB - We study the photogeneration of topological solitons in trans-polyacetylene and their time evolution using ab initio excited-state dynamics. The system is excited to the optically allowed 1(1)Bu state, and the atoms are then propagated classically using quantum mechanical forces computed using hybrid time-dependent density functional theory (TD-DFT). A soliton/antisoliton pair nucleates spontaneously and creates two independent solitons moving at constant velocity, similar to simulations based on uncorrelated lattice models like the Su Schrieffer-Heeger (SSH) Hamiltonian [Su, W. P.; Schrieffer, J. R.; Heeger, A. J. Phys. Rev. Lett. 1979, 42, 1698]. At T = 0, the solitons coalesce into bound pairs with a two-soliton functional form, whereas chaotic dynamics, in the form of 2-bounce resonances, is observed at soliton/antisoliton collisions at T ? 0. This behavior is related to the onset of a strong correlation regime at short intersoliton distance, which is not accounted for by SSH simulations. PMID- 26262672 TI - Buckybomb: Reactive Molecular Dynamics Simulation. AB - Energetic materials, such as explosives, propellants, and pyrotechnics, are widely used in civilian and military applications. Nanoscale explosives represent a special group because of the high density of energetic covalent bonds. The reactive molecular dynamics (ReaxFF) study of nitrofullerene decomposition reported here provides a detailed chemical mechanism of explosion of a nanoscale carbon material. Upon initial heating, C60(NO2)12 disintegrates, increasing temperature and pressure by thousands of Kelvins and bars within tens of picoseconds. The explosion starts with NO2 group isomerization into C-O-N-O, followed by emission of NO molecules and formation of CO groups on the buckyball surface. NO oxidizes into NO2, and C60 falls apart, liberating CO2. At the highest temperatures, CO2 gives rise to diatomic carbon. The study shows that the initiation temperature and released energy depend strongly on the chemical composition and density of the material. PMID- 26262673 TI - Bioaccessibility of Polyphenols from Plant-Processing Byproducts of Black Carrot (Daucus carota L.). AB - Plant-processing byproducts of black carrot represent an important disposal problem for the industry; however, they are also promising sources of polyphenols, especially anthocyanins. The present study focused on the changes in polyphenols from black carrot, peel, and pomace during in vitro gastrointestinal digestion. Total phenolic content (TPC), total monomeric anthocyanin content (TMAC), and total antioxidant capacity (TAC) were determined using spectrophotometric methods, whereas identification and quantification of polyphenols were carried out using UPLC-ESI-MS(E) and HPLC-DAD, respectively. TPC, TMAC, and TAC significantly decreased (23-82%) as a result of in vitro gastrointestinal digestion. Nevertheless, the amount of pomace anthocyanins released at all stages of in vitro gastrointestinal digestion was higher than black carrot anthocyanins, suggesting that pomace may be a better source of bioaccessible anthocyanins. Overall, the current study highlighted black carrot byproducts as substantial sources of polyphenols, which may be used to enrich food products. PMID- 26262674 TI - Lipid analysis of developing Camelina sativa seeds and cultured embryos. AB - Camelina sativa is a cultivated oilseed rich in triacylglycerols containing oleic, linoleic, alpha-linolenic and eicosenoic acids. As it holds promise as a model species, its lipid synthesis was characterized in vivo and in culture. Lipid accumulates at a maximum rate of about 26 MUg/day/seed (11.5 mg lipid/day/g fresh seed weight), a rate comparable with other oilseeds. Noteworthy is a late stage surge in alpha-linolenic acid accumulation. Small amounts of unusual epoxy and hydroxy fatty acids are also present in the triacylglycerols. These include 15,16-epoxy- and 15-hydroxy-octadecadienoic acids and homologous series of omega7 hydroxy-alk-omega9-enoic and omega9/10-hydroxy-alkanoic acids. Mid-maturation embryos cultured in vitro have growth and lipid deposition rates and fatty acid compositions that closely match that of seeds, but extended culture periods allow these rates to rise and surpass those observed in planta. Optimized thin layer chromatography systems for characterization of labeled products from acetate or glycerol labeling are described. Glycerol label is only found in acylglycerols, largely as the intact glyceryl backbone, but acetate can label acyl groups and sterols, the latter to a much higher relative specific activity. This presumably occurs because mevalonic acid precursor is derived from the non-plastid pool of acetyl-CoA that is also the source for malonyl-CoA to drive FAE1-dependent chain elongation. Particular attention has been paid to the separation of sterols and diacylglycerols, and to hydrogenation of triacylglycerols to simplify their analysis. These improved methods will allow more accurate analyses of the fluxes of lipid metabolism in cultured plant embryos. PMID- 26262675 TI - Isolation and molecular characterization of extracellular vesicles. PMID- 26262676 TI - Bridging the opposite chemistries of tantalum and tungsten polyoxometalates. AB - The disparate solubility, redox activity, and pH stability of the group V and group VI polyoxometalates (POMs) confer very different functionality on these species, and tailoring cluster properties by varying the ratio of group V to group VI metals poses both an opportunity and a synthetic challenge. A classic series of studies reported over 40 years ago provided some insight into W/Nb POMs, from which researchers have built on to date. However, the analogous W/Ta series has never been addressed in a systematic manner. Three members of this W/Ta series are presented here, synthesized from simple oxo- and peroxocoltanate precursors. [Ta3W3O19](5-) displays the Lindqvist-type structure, while [TaW9O32](5-) and [Ta2W8O32](6-) are isostructural with decatungstate ([W10O32](4 )). Additionally, the use of peroxoniobate instead of hexaniobate as the starting material drives the formation of the decatungstate-type structure [NbW9O32](5-) instead of the Lindqvist ion that was established to be the foundational cluster geometry in prior work. The electronic structure of the Nb/Ta substituted decatungstates is directly related to the degree of substitution inasmuch as the HOMO-LUMO energy gap (Egap) slightly increases as more Nb/Ta atoms are incorporated into the structure. The poor mixing of the d-orbitals of Nb/Ta and W is responsible for the observed trends in the UV spectra and cyclic voltammetry. Moreover, the stability of the molecular frameworks in the gas phase is also related to the extent of substitution as revealed by electrospray mass spectrometry (ESI-MS). PMID- 26262677 TI - Correction: Genetic Variants of IkappaB Kinase beta (IKBKB) and Polymerase beta (POLB) Were Not Associated with Systemic Lupus Erythematosus Risk in a Chinese Han Population. PMID- 26262678 TI - Organized Sport Participation Is Associated with Higher Levels of Overall Health Related Physical Activity in Children (CHAMPS Study-DK). AB - INTRODUCTION: Many children fail to meet international guideline recommendations for health-related activity (>=60 minutes/day of moderate-to-vigorous physical activity [MVPA]), and intervention studies to date have reported negligible effects. OBJECTIVE: Explore the associations of organized leisure-time sport participation with overall physical activity levels and health-related physical activity guideline concordance. METHODS: This prospective cohort study was nested in the Childhood Health, Activity, and Motor Performance School Study Denmark. Study participants were a representative sample of 1124 primary school students. Organized leisure-time sport participation was reported via text messaging and physical activity was objectively measured over seven days with accelerometry. Associations between sport participation and physical activity level were explored with multilevel mixed-effects regression models and reported with beta coefficients (b) and adjusted odds ratios (aOR). RESULTS: Participants were 53% female, with mean(SD) age = 8.4(1.4) years. Boys were more active than girls (p<0.001), and physical activity levels and guideline concordance decreased with age (p<0.001). Soccer participation at any frequency was associated with greater overall MVPA (b[95% CI] = 0.66[0.20,1.13] to 2.44[1.44,3.44]). Depending on participation frequency, this equates to 5-20 minutes more MVPA on the average day and 3 to 15 fold increased odds of achieving recommended levels of health related physical activity (aOR[95%CI] = 3.04[1.49,6.19] to 14.49[1.97,106.56]). Similar associations were identified among children playing handball at least twice per week. Relationships with other sports (gymnastics, basketball, volleyball) were inconsistent. CONCLUSIONS: Many children, particularly girls and those in higher grade levels do not adhere to health-related physical activity recommendations. Organized leisure-time sport participation may be a viable strategy to increase overall health-related physical activity levels and international guideline concordance in children. PMID- 26262679 TI - Antibiotic Exposure and Other Risk Factors for Antimicrobial Resistance in Nasal Commensal Staphylococcus aureus: An Ecological Study in 8 European Countries. AB - OBJECTIVES: Antimicrobial resistance (AMR) has become a global public health concern which threatens the effective treatment of bacterial infections. Resistant Staphylococcus aureus (including MRSA) increasingly appears in individuals with no healthcare associated risks. Our study assessed risk factors for nasal carriage of resistant S. aureus in a multinational, healthy, community based population, including ecological exposure to antibiotics. METHODS: Data were collected in eight European countries (Austria, Belgium, Croatia, France, Hungary, the Netherlands, Spain and Sweden). Commensal AMR patterns were assessed by collecting 28,929 nasal swabs from healthy persons (aged 4+). Ecological exposure to antibiotics was operationalized as systemic antibiotic treatment patterns, extracted from electronic medical records of primary care practices in which the participants were listed (10-27 per country). A multilevel analysis related AMR in nasal commensal S. aureus to antibiotic exposure and other risk factors (e.g. age and profession). RESULTS: Of the 6,093 S. aureus isolates, 77% showed resistance to at least one antibiotic. 7.1% exhibited multidrug resistance (defined as resistance to 3 or more antibiotic classes), and we found 78 cases MRSA (1.3%). A large variation in antibiotic exposure was found between and within countries. Younger age and a higher proportion of penicillin prescriptions in a practice were associated with higher odds for carriage of a resistant S. aureus. Also, we found higher multidrug resistance rates in participants working in healthcare or nurseries. CONCLUSIONS: This study indicates that in a population with no recent antibiotic use, the prescription behavior of the general practitioner affects the odds for carriage of a resistant S. aureus, highlighting the need for cautious prescribing in primary care. Finally, since variation in AMR could partly be explained on a national level, policy initiatives to decrease AMR should be encouraged at the national level within Europe. PMID- 26262680 TI - Anorectal Chlamydia trachomatis Load Is Similar in Men Who Have Sex with Men and Women Reporting Anal Sex. AB - BACKGROUND: Anorectal Chlamydia trachomatis (chlamydia) is frequently diagnosed in men who have sex with men (MSM) and in women, but it is unknown whether these infections are comparable in clinical impact and transmission potential. Quantifying bacterial load and identifying determinants associated with high bacterial load could provide more insight. METHODS: We selected a convenience sample of MSM who reported anal sex (n = 90) and women with concurrent urogenital/anorectal chlamydia who reported anal sex (n = 51) or did not report anal sex (n = 61) from the South Limburg Public Health Service's STI unit. Bacterial load (Chlamydia/ml) was quantified for all samples and log transformed for analyses. Samples with an unquantifiable human leukocyte antigen (n = 9) were excluded from analyses, as they were deemed inadequately sampled. RESULTS: The mean log anorectal chlamydia load (3.50) was similar for MSM and women who reported having anal sex (3.80, P = 0.21). The anorectal chlamydia load was significantly higher in these groups than in women who did not report having anal sex (2.76, P = 0.001). Detectable load values ranged from 1.81-6.32 chlamydia/ml for MSM, 1.74-7.33 chlamydia/ml for women who reported having anal sex and 1.84 6.31 chlamydia/ml for women who did not report having anal sex. Symptoms and several other determinants were not associated with anorectal chlamydia load. CONCLUSIONS: Women who did not report anal sex had lower anorectal loads, but they were within a similar range to the other two groups. Anorectal chlamydia load was comparable between MSM and women who reported anal sex, suggesting similar transmission potential. PMID- 26262681 TI - Forest Cover Estimation in Ireland Using Radar Remote Sensing: A Comparative Analysis of Forest Cover Assessment Methodologies. AB - Quantification of spatial and temporal changes in forest cover is an essential component of forest monitoring programs. Due to its cloud free capability, Synthetic Aperture Radar (SAR) is an ideal source of information on forest dynamics in countries with near-constant cloud-cover. However, few studies have investigated the use of SAR for forest cover estimation in landscapes with highly sparse and fragmented forest cover. In this study, the potential use of L-band SAR for forest cover estimation in two regions (Longford and Sligo) in Ireland is investigated and compared to forest cover estimates derived from three national (Forestry2010, Prime2, National Forest Inventory), one pan-European (Forest Map 2006) and one global forest cover (Global Forest Change) product. Two machine learning approaches (Random Forests and Extremely Randomised Trees) are evaluated. Both Random Forests and Extremely Randomised Trees classification accuracies were high (98.1-98.5%), with differences between the two classifiers being minimal (<0.5%). Increasing levels of post classification filtering led to a decrease in estimated forest area and an increase in overall accuracy of SAR derived forest cover maps. All forest cover products were evaluated using an independent validation dataset. For the Longford region, the highest overall accuracy was recorded with the Forestry2010 dataset (97.42%) whereas in Sligo, highest overall accuracy was obtained for the Prime2 dataset (97.43%), although accuracies of SAR-derived forest maps were comparable. Our findings indicate that spaceborne radar could aid inventories in regions with low levels of forest cover in fragmented landscapes. The reduced accuracies observed for the global and pan continental forest cover maps in comparison to national and SAR-derived forest maps indicate that caution should be exercised when applying these datasets for national reporting. PMID- 26262682 TI - Post-Progression Survival after EGFR-TKI for Advanced Non-Small Cell Lung Cancer Harboring EGFR Mutations. AB - BACKGROUND: Non-small cell lung cancer (NSCLC) patients that harbor epidermal growth factor receptor (EGFR) mutations benefit from receiving an EGFR-tyrosine kinase inhibitor (TKI); however, post-progression survival (PPS) after EGFR-TKI treatment has not been sufficiently studied. METHODS: We retrospectively reviewed the clinical data from stage IV or recurrent NSCLC patients who harbored EGFR mutations and who received EGFR-TKI as their first-line treatment in our institute between 2009 and 2011. RESULTS: In total, 36 patients received EGFR-TKI treatment as their first-line therapy. Of those 36 patients, 30 experienced recurrence and were enrolled in this study. The median progression-free survival (PFS) of these patients was 8.2 months. Twelve patients received EGFR-TKI treatment beyond the diagnosis of progressive disease (PD), and 8 received second line therapy. The PPS after EGFR-TKI treatment was 9.1 months, and survival after the termination of EGFR-TKI treatment in those patients treated with second-line chemotherapy was 13.9 months. The site of relapse was investigated and PFS in EGFR-TKI-treated patients with relapse in the brain (11.6 months) showed a trend toward a longer PFS compared with patients with relapse at other sites (8.2 months). The median PPS after EGFR-TKI treatment also showed the same trend in each group (12.9 and 9.2 months, respectively). CONCLUSIONS: The PPS after EGFR TKI treatment failure was 9.1 months, while the survival of patients who underwent second-line chemotherapy after the termination of EGFR-TKI treatment was 13.9 months, comparable with the overall survival of EGFR mutation-negative patients, as previously reported. The prognosis of these NSCLC patients with EGFR mutations varied according to the sites of recurrence after first-line EGFR-TKI treatment. Of particular note was the prognosis of patients with brain metastases, which tended to be better than that of patients with metastases to other sites. PMID- 26262683 TI - Development of a Multiple Loci Variable Number of Tandem Repeats Analysis (MLVA) to Unravel the Intra-Pathovar Structure of Pseudomonas syringae pv. actinidiae Populations Worldwide. AB - The bacterial canker of kiwifruit by Pseudomonas syringae pv. actinidiae is an emblematic example of a catastrophic disease of fruit crops. In 2008 a new, extremely virulent form of the pathogen emerged and rapidly devastated many Actinidia spp. orchards all over the world. In order to understand differences in populations within this pathovar and to elucidate their diffusion and movements on world scale, it is necessary to be able to quickly and on a routine basis compare new isolates with previous records. In this report a worldwide collection of 142 strains was analyzed by MLVA, chosen as investigative technique for its efficacy, reproducibility, simplicity and low cost. A panel of 13 Variable Number of Tandem Repeats (VNTR) loci was identified and used to describe the pathogen population. The MLVA clustering is highly congruent with the population structure as previously established by other molecular approaches including whole genome sequencing and correlates with geographic origin, time of isolation and virulence. For convenience, we divided the VNTR loci in two panels. Panel 1 assay, using six loci, recognizes 23 different haplotypes, clustered into ten complexes with highest congruence with previous classifications. Panel 2, with seven VNTR loci, provides discriminatory power. Using the total set of 13 VNTR loci, 58 haplotypes can be distinguished. The recent hypervirulent type shows very limited diversity and includes, beside the strains from Europe, New Zealand and Chile, a few strains from Shaanxi, China. A broad genetic variability is observed in China, but different types are also retrievable in Japan and Korea. The low virulent strains cluster together and are very different from the other MLVA genotypes. Data were used to generate a public database in MLVAbank. MLVA represents a very promising first-line assay for large-scale routine genotyping, prior to whole genome sequencing of only the most relevant samples. PMID- 26262684 TI - In Vivo Effects of Free Form Astaxanthin Powder on Anti-Oxidation and Lipid Metabolism with High-Cholesterol Diet. AB - Astaxanthin extracted from Pomacea canaliculata eggs was made into free-form astaxanthin powder (FFAP) and its effects on lipid metabolism, liver function, antioxidants activities and astaxanthin absorption rate were investigated. 45 hamsters were split into 5 groups and fed with normal diet, high-cholesterol control (0.2% cholesterol), 1.6FFAP (control+1.6% FFAP), 3.2FFAP (control+3.2% FFAP) and 8.0FFAP (control+8.0% FFAP), respectively, for 6 weeks. FFAP diets significantly decreased the liver total cholesterol, triglyceride levels and increased liver fatty acids (C20:5n3; C22:6n3) compositions. It decreased plasma alanine aminotransferase and aspartate aminotransferase. In terms of anti oxidative activities, we found 8.0 FFAP diet significantly decreased plasma and liver malonaldehyde (4.96+/-1.96 MUg TEP eq./mL and 1.56+/-0.38 MUg TEP eq./g liver) and liver 8-isoprostane levels (41.48+/-13.69 MUg 8-ISOP/g liver). On the other hand, it significantly increased liver catalase activity (149.10+/-10.76 MUmol/min/g liver), Vitamin C (2082.97+/-142.23 MUg/g liver), Vitamin E (411.32+/ 81.67 MUg/g liver) contents, and glutathione levels (2.13+/-0.42 mg GSH eq./g liver). Furthermore, 80% of astaxanthin absorption rates in all FFAP diet groups suggest FFAP is an effective form in astaxanthin absorption. Finally, astaxanthin was found to re-distribute to the liver and eyes in a dose dependent manner. Taken together, our results suggested that the appropriate addition of FFAP into high cholesterol diets increases liver anti-oxidative activity and reduces the concentration of lipid peroxidase and therefore, it may be beneficial as a material in developing healthy food. PMID- 26262685 TI - Effects of Carbenoxolone on the Canine Pituitary-Adrenal Axis. AB - Cushing's disease caused by pituitary corticotroph adenoma is a common endocrine disease in dogs. A characteristic biochemical feature of corticotroph adenomas is their relative resistance to suppressive negative feedback by glucocorticoids. The abnormal expression of 11beta-hydroxysteroid dehydrogenase (11HSD), which is a cortisol metabolic enzyme, is found in human and murine corticotroph adenomas. Our recent studies demonstrated that canine corticotroph adenomas also have abnormal expression of 11HSD. 11HSD has two isoforms in dogs, 11HSD type1 (HSD11B1), which converts cortisone into active cortisol, and 11HSD type2 (HSD11B2), which converts cortisol into inactive cortisone. It has been suggested that glucocorticoid resistance in corticotroph tumors is related to the overexpression of HSD11B2. Therefore it was our aim to investigate the effects of carbenoxolone (CBX), an 11HSD inhibitor, on the healthy dog's pituitary-adrenal axis. Dogs were administered 50 mg/kg of CBX twice each day for 15 days. During CBX administration, no adverse effects were observed in any dogs. The plasma adrenocorticotropic hormone (ACTH), and serum cortisol and cortisone concentrations were significantly lower at day 7 and 15 following corticotropin releasing hormone stimulation. After completion of CBX administration, the HSD11B1 mRNA expression was higher, and HSD11B2 mRNA expression was significantly lower in the pituitaries. Moreover, proopiomelanocortin mRNA expression was lower, and the ratio of ACTH-positive cells in the anterior pituitary was also significantly lower after CBX treatment. In adrenal glands treated with CBX, HSD11B1 and HSD11B2 mRNA expression were both lower compared to normal canine adrenal glands. The results of this study suggested that CBX inhibits ACTH secretion from pituitary due to altered 11HSD expressions, and is potentially useful for the treatment of canine Cushing's disease. PMID- 26262686 TI - A Novel Matrix Protein Hic31 from the Prismatic Layer of Hyriopsis Cumingii Displays a Collagen-Like Structure. AB - In this study, we clone and characterize a novel matrix protein, hic31, from the mantle of Hyriopsis cumingii. The amino acid composition of hic31 consists of a high proportion of Glycine residues (26.67%). Tissue expression detection by RT PCR indicates that hic31 is expressed specifically at the mantle edge. In situ hybridization results reveals strong signals from the dorsal epithelial cells of the outer fold at the mantle edge, and weak signals from inner epithelial cells of the same fold, indicating that hic31 is a prismatic-layer matrix protein. Although BLASTP results identify no shared homology with other shell-matrix proteins or any other known proteins, the hic31 tertiary structure is similar to that of collagen I, alpha 1 and alpha 2. It has been well proved that collagen forms the basic organic frameworks in way of collagen fibrils and minerals present within or outside of these fibrils. Therefore, hic31 might be a framework matrix protein involved in the prismatic-layer biomineralization. Besides, the gene expression of hic31 increase in the early stages of pearl sac development, indicating that hic31 may play important roles in biomineralization of the pearl prismatic layer. PMID- 26262687 TI - Fast, Simple and Accurate Handwritten Digit Classification by Training Shallow Neural Network Classifiers with the 'Extreme Learning Machine' Algorithm. AB - Recent advances in training deep (multi-layer) architectures have inspired a renaissance in neural network use. For example, deep convolutional networks are becoming the default option for difficult tasks on large datasets, such as image and speech recognition. However, here we show that error rates below 1% on the MNIST handwritten digit benchmark can be replicated with shallow non convolutional neural networks. This is achieved by training such networks using the 'Extreme Learning Machine' (ELM) approach, which also enables a very rapid training time (~ 10 minutes). Adding distortions, as is common practise for MNIST, reduces error rates even further. Our methods are also shown to be capable of achieving less than 5.5% error rates on the NORB image database. To achieve these results, we introduce several enhancements to the standard ELM algorithm, which individually and in combination can significantly improve performance. The main innovation is to ensure each hidden-unit operates only on a randomly sized and positioned patch of each image. This form of random 'receptive field' sampling of the input ensures the input weight matrix is sparse, with about 90% of weights equal to zero. Furthermore, combining our methods with a small number of iterations of a single-batch backpropagation method can significantly reduce the number of hidden-units required to achieve a particular performance. Our close to state-of-the-art results for MNIST and NORB suggest that the ease of use and accuracy of the ELM algorithm for designing a single-hidden-layer neural network classifier should cause it to be given greater consideration either as a standalone method for simpler problems, or as the final classification stage in deep neural networks applied to more difficult problems. PMID- 26262688 TI - [THE JOURNAL'S SPINE]. PMID- 26262689 TI - [NUTRITION, SURGERY AND PROGRAMMES OF MULTIMODAL REHABILITATION]. PMID- 26262691 TI - [FREQUENTLY USED VEGETABLE OILS IN SOUTH AMERICA: FEATURES AND PROPERTIES]. AB - In recent decades, the consumption of vegetable oils has increased in our society, being an important part of the diet worldwide. South America is a major producer of an important variety of vegetable oils. The composition of vegetable oils is not standard as it varies greatly in the amount of saturated, monounsaturated and polyunsaturated fatty acids, and particularly in the amounts of omega-6 and omega-3, which are associated with the source either plant species, seed, plant or fruit, providing different nutritional benefits. The purpose of this article is to review and update the data and evidence about the consumption of oils produced and commercialized in South America, such as soybean oil, corn, palm, sunflower, canola and olive oils, and also to determine health effects from studies related with the topic. PMID- 26262690 TI - [BREAST MILK AS A VEHICLE OF TRANSMISSION OF VIRUS]. AB - INTRODUCTION: breast milk, besides being a source of feeding for children, it can be a vehicle for transmission of some infectious diseases. AIM: to revise the main viral agents which can be acquired for children through breast milk and its possible clinical implication. MATERIAL: literature search was made in different databases and books. RESULTS: date on the human immunodeficiency virus type 1 and 2, human T-lymphotropic virus, cytomegalovirus, hepatitis A, B and C virus, herpes simplex virus types 1 and 2, varicella zoster virus and other viruses are exposed in detail. CONCLUSIONS: the human immunodeficiency virus type 1 and 2, human T-lymphotropic virus and cytomegalovirus in preterm newborns or low birth weight are the most frequent viruses that cause infection or illness in children as a result of its transmission through breast milk. For other viruses, such as varicella zoster, hepatitis A or hepatitis B, the immunoprophylaxis of the newborn, through the administration of immunoglobulin and vaccine, protect children against their transmission. PMID- 26262692 TI - USEFULNESS OF Beta-HYDROXY-Beta-METHYLBUTYRATE (HMB) SUPPLEMENTATION IN DIFFERENT SPORTS: AN UPDATE AND PRACTICAL IMPLICATIONS. AB - INTRODUCTION: although ?-hydroxy-?-methylbutyrate (HMB) is generally marketed as a supplement for increasing muscle mass and strength, it is still not fully understood how and in which particular sports and conditions HMB can be more effective. AIMS: the primary purpose of this review is to update and summarize the current knowledge about the usefulness of HMB and to organize this information by different sports with specific reference to sports with high wear and tear phenomena as soccer, rugby or football. METHODS: a search was performed in PubMed database. This review presents the results about HMB use in sport. RESULTS: the articles identified in this review support the notion that HMB could help to attenuate tissue catabolism and initiate muscle anabolism particularly in untrained individuals exposed to strenuous exercise or when trained individual are exposed to periods of high physical stress. HMB could therefore be applied in some specific periods of athlete's season where there are high-intensity training periods, high density of competitions and little recovery time between them, starting recovery phases from an injury period and/or any other different situation where performance or recovery could be affected by a great catabolic environment. CONCLUSION: this update contributes to clarify and define possible mechanisms and/or effectiveness of HMB supplementation related to endurance sports (i.e. cycling and athletics), strength-power sports (i.e. resistance training, football, rugby, soccer, judo, waterpolo and rowing) and recreational activities. PMID- 26262693 TI - NUTRITIONAL AND TOXICOLOGICAL ASPECTS OF SPIRULINA (ARTHROSPIRA). AB - Undernutrition constitutes a public health problem particularly in developing countries. The utilization of algae, particularly Spirulina, as a functional food was suggested decades ago due to the fact that it is not only a protein-dense food source, but because its amino acid profile is considered as of high biologic value protein content. Spirulina provides essential fats (e.g., gamma-linolenic oleic acids), concomitant to low content nucleic acids. It also has an exceptionally high content of vitamin B12, is a good source of beta-carotene, iron, calcium and phosphorous. Moreover, Spirulina has also proven to have good acceptance as of its organoleptic properties (thus making it a possible prospect for food or a nutrition supplement) and it has not exhibited neither acute nor chronic toxicities, making it safe for human consumption. PMID- 26262694 TI - [THE INFLUENCE OF THE POLYUNSATURATED FATTY ACIDS IN THE PREVENTION AND PROMOTION OF CANCER]. AB - INTRODUCTION: each year, almost eight million people die in the world due to cancer. Carcinogenesis is a process that involves a series of structural alterations of the DNA which affect its stability and prevents proper cell reproduction and development. There are many factors that influence the cancer etiology. Nutritional factors are included among them. The polyunsaturated fatty acids (PUFA) intake is associated more and more with the prevention and development of chronic diseases with an inflammatory component such as cancer. OBJECTIVE: this work reviews the latest bibliography on the PUFA and its relationship with the cancer, mainly of prostate, breast and colon cancer. METHODS: the preliminary search resulted in 92 selected references. But, after their review, 40 experimental studies, in animals and in vitro, and epidemiological studies have been included. RESULTS: experimental studies in animals and in vitro reviewed show a protective effect of omega3 PUFA against cancer. However, human studies are contradictory; although it is clear there is evidence of the protective effect of the omega3 PUFA in colon cancer prevention. CONCLUSION: the relationship between omega6 and omega3 PUFA of the diet against the cancer risk is becoming increasingly important, but further studies are needed to confirm their influence on the development of this disease. PMID- 26262695 TI - [NUTRITIONAL COMPONENTS AND MACULAR DEGENERATION AGE-RELATED]. AB - OBJECTIVE: nutritional components such as antioxidants may modify the risk of Macular Degeneration Age-related (AMD). This article is a systematic review of published studies relating to the modification of lifestyle, nutrition and vitamin intake to prevent or delay the onset or progression of Macular Degeneration Age-related (AMD). RESULTS: the analysis of the results of research consulted shows that AMD is one of the most common causes of blindness in individuals over 55 years. AMD is characterized by decreased vision, metamorphopsias, macropsias, micropsias and central scotoma. Disease that must be diagnosed early because it can lead to irreversible blindness. Between components of the diet in many epidemiological studies have shown an inverse association with AMD and are reviewed in this paper are: vitamins (vitamin E and C), minerals (eg. zinc, selenium, manganese and copper) and carotenoids. CONCLUSIONS: there is substantial evidence that can be applied nutritional support for patients with AMD. This requires determining the nutritional benefits of these nutrients (vitamins, minerals and carotenoids) or nutraceutical foods for health in this group of patients. PMID- 26262696 TI - [EVALUATION OF THE BODY ADIPOSITY INDEX IN PREDICTING PERCENTAGE BODY FAT AMONG COLOMBIAN ADULTS]. AB - OBJECTIVE: the body adiposity index (BAI) is a new simplistic method for predicting body fat percentage (BF%) via a simple equation of hip circumference to height. Up to now, few studies have evaluated the performance of BAI in determining excess fat in Colombians. The aim of this study was to evaluate the usefulness of BAI as a predictor of body fat in among Colombian adults. METHODS: cross-sectional study carried out in a sample of 204 male belonging to the education sector from Bogota, Colombia. BAI was calculated based on the equation reported in the Bergman et al. %BF determined by tetrapolar bioimpedance analysis (BIA) was used as the reference measure of adiposity. Bland-Altman analysis was used to assess the agreement between the two methods: BAI and BIA. Associations between anthropometric measures of adiposity were investigated by Pearson correlation analysis. RESULTS: in general pupulation, the BAI overestimates %BF (mean difference: 12.5 % [95%CI = -4.04 % to -21.02 %]), mainly at lower levels of adiposity (mean difference: 10.2 +/- 3.3). Significant correlations were found between BAI and all measurements, being the strongest-moderate correlation with %BF (r = 0.777, p < 0.001), waist to height ratio (r = 0.557, p < 0.001) and BMI (r = 0.480, p < 0.001). CONCLUSION: the results of this investigation indicate that BAI results in large individual errors when predicting BF% among Colombian adults and has a tendency to provide overestimated values as BF% decreases. Therefore, this method can be a useful tool to predict %BF in Colombian adults, although it has some limitations. PMID- 26262697 TI - [CONSUMPTION OF CHEESE AND MILK AND CHRONIC DISEASES ASSOCIATED WITH OBESITY, FRIEND OR FOE?]. AB - Cardiovascular diseases (CVD) and especially the obstruction of the coronary arteries are the main health expenditure in most of the countries. However, France, according to WHO, has the lowest mortality from these causes but shows a high dietary intake of saturated fats, known as the French paradox. In addition, consumption of wine, small food intakes, regular exercise, increased intake of fruits and vegetables rich in dietary fiber, flavonoids and phytosterols and also cheese comsumption, are factors which together contribute to the paradox. There areseveral studies which link fat intake and CVD but not showing a high correlation. This fact could be justified by the divergent effect of saturated fat on lipoproteins. Dairy products content saturated fats, however recentlystudies have found an inverse correlation between its consumption and CVD, possibly due to their content of trans fatty acid palmitoleic, which allows to increase the levels of HDL cholesterol, decrease C reactive protein and triglicerides. In general, dairy products have an important variety of nutrients which can have several health benefits improving the response to insulin, adiponectin levels increase and decrease the presence of obesity, among other effects. Meanwhile, consumption of cheese, may have positive health effects, for example, is able toprevent cardiovascular infarctions, descend plasma TAGs and increases HDL cholesterol. This paper shows the results of several studies linking consumption of cheese with non-communicable diseases with special emphasis on CVD. The displayed data allow us to conclude that regular consumption has more beneficial than detrimental effects. PMID- 26262698 TI - [NUTRITIONAL STATUS AND PHYSICAL CAPACITY IN 4 TO 7-YEAR-OLD STUDENTS IN A CHILEAN PUBLIC SCHOOL 2014]. AB - INTRODUCTION: overweight and obesity in children have experienced a significant increase around the world, however, there are regional differences due to many factors. Furthermore, evidence have showed that physical capacity in children has been affected as well. For this reason, the study goal was to assess nutritional status and physical capacity in 4 to 7-year-old children in a public school from South Chile. METHODS: 351 students (6.1 years, SD = 1.13; 47.3% men) completed the study. To determine nutritional status, body mass index and Z-scores from World Health Organisation were used. Body fat percentage was measured with skinfold anthropometry. To assess physical capacity, 6-minute walking test (6MWT) was used. RESULTS: overweight prevalence was 27.0% (range 21-32%), while obesity had 39.9% (range 33-50%), no gender differences were observed (p = 0.84). Mean body fat percentage was 19.1% in men and 20.9% in women (p = 0.02). For 6MWT, differences were found for age (p < 0.001) with an overall range of 421.5 to 540.2 mt. DISCUSSION: our results showed a high prevalence of overweight and obese students. These results are higher than observed in other regions around the world. This study is a call for action in promoting healthy lifestyle through comprehensive programs in public schools. PMID- 26262699 TI - [PRE-OPERATIVE IRON DEFICIENCY IN BARIATRIC SURGERY: DIAGNOSIS AND TREATMENT]. AB - INTRODUCTION: chronic inflammation induced by obesity alters iron homeostasis leading to mild /moderate iron deficiency and anaemia. Between 14% and 43% of patients may suffer from iron deficiency without anaemia before surgery. The management of peri-operative iron deficiency improves patient outcome and quality of life. Under certain circumstances intravenous (IV) iron must be considered. IV iron (which may avoid iron blockage in enterocytes and macrophages) has turned out to be a safe and efficient alternative. Objetives: 1) To assess the prevalence of iron deficiency in morbidly obese patients candidates for bariatric surgery. 2) Assess whether supplementation of parenteral iron in iron-deficient patients is effective in preventing the decrease in hematocrit after surgery. MATERIALS AND METHODS: prospective, observational study which included 89 morbidly obese patients who underwent bariatric surgery. The population was divided according to whether or not patients had pre-op iron deficiency, and post op evolution was analyzed. Iron-deficient patients were supplemented with 500 mg of intravenous (IV) carboximaltose and were evaluated post-op. RESULTS: twenty three patients (25.8%) presented preop iron deficiency pre-operatively while six (6.74%) had anemia. 74.2% (66 patients) had no iron deficiency. The group without iron deficiency at one month of surgery had the following laboratory values: Hematocrit: 41.30% +/- 3.77; hemoglobin: 13.64 g/l +/- 1.25 and transferrin saturation: 30.55 %. The patients with pre-op iron deficiency had the following values: Hematocrit: 40.40% +/- 3.03; hemoglobin: 13.40 g/l +/- 1.07; transferrin saturation: 15.50% +/- 4.18, and ferritin: 87.10 ng/ml +/- 81.23. Post-op hematocrit reduction was 38.40% +/- 3.17 (p: 0.034). In iron-deficient patients without IV iron supplementation (n=15), hematocrit and hemoglobin were 41.2% +/- 2.5 and 13.7 g/l +/- 0.9 respectively with post-op reduction (37.5% +/- 3.4 and 12.3 g/l p < 0.05). IV iron supplementation in iron-deficient patients (n = 9) increased hemoglobin (13.5 g/l +/- 0.7), compared with the pre-op (12.8 g/l +/- 1.2; p: 0.05), as well as transferrin saturation and ferritin. One month after surgery there were no significant changes in hematocrit (pre-op: 39%, post-op: 40% p: > 0.05). DISCUSSION: 1) Almost 26% of patients present pre-op iron deficiency. 2) Treatment with IV iron seems to be efficient to prevent hematocrit reduction and to improve iron metabolism in pre-op iron-deficient patients. In patients without iron deficiency, hematocrit and iron metabolism remain normal one month after surgery without the need for iron supplementation. PMID- 26262700 TI - PROTEIN MALNUTRITION INCIDENCE COMPARISON AFTER GASTRIC BYPASS VERSUS BILIOPANCREATIC DIVERSION. AB - BACKGROUND: bariatric surgery is widely employed nowadays. Nutritional complications following malabsorptive bariatric surgery are common. OBJECTIVES: to compare protein malnutrition incidence, the amount of protein intake and the influence of various risk factors in patients undergoing Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD). METHODS: retrospective study comparing the development of hypoalbuminemia in 92 patients undergoing BPD and 121 RYGB, before surgery and 3, 6, 12, 18 and 24 months after it. Protein intake was estimated by serum prealbumin. The influence of prior body mass index (BMI), age and sex was analyzed. RESULTS: hypoprealbuminemia was found in around 40% of patients 3 months after both procedures, decreasing to about 10% after 2 years of surgery. Hypoalbuminemia incidence was close to 20% in the first post-surgery year in BPD, persisting in 10-15% of cases thereafter. After RYGB, hypoalbuminemia incidence was lower (5-9% in all postoperative follow-up measurements). During the first year after surgery, hypoalbuminemia was more frequent after BPD than after RYGB (at the 3rd month (OR:3.9; p=0.006; 95%CI:1.5 10.4), 6th (OR:5.0; p=0.002; 95% CI:1.8-13.8), and at the 12th month (OR:4.4;p=0.007;95%;CI:1.5-12.8)), but not after the first year. A higher preoperative BMI favored it (OR: 1.03; p=0.046; 95% CI:1-1.06), as well as greater age during the first 6 months. CONCLUSION: Patients with BPD had a higher risk for hypoproteinemia than those undergoing RYGB, especially during the first year post-surgery. Higher preoperative BMI, and age (in the short-term period) could have a significant inverse relation to hypoproteinemia. PMID- 26262701 TI - SHORT-TERM CHANGES IN MACRONUTRIENT INTAKE IN MORBIDLY OBESE PATIENTS UNDERGOING BILIOPANCREATIC DIVERSION: A LONGITUDINAL STUDY. AB - INTRODUCTION: biliopancreatic diversion (BPD) has been shown to be one of the most effective techniques for losing weight, although nutritional education also might play an important role. Our aim was to determine the effect of the combination of a nutrition educational program (NEP) and BPD on changes in the intake of energy and macronutrients after the surgery. METHODOLOGY: this longitudinal study included all patients eligible for BPD who filled in a dietary record. Two assessments were performed: six weeks before and twelve months after surgery. The nutrition educational program was given two weeks after surgery by a registered dietitian and a 3-day food record was collected for further analysis at both of the assessments. RESULTS: 68 patients were included. The percentage of excess weight loss was 60.76% (SD 14.50%). A year after the surgery there was a reduction of energy (-602.27 kcal [SD 930.19 kcal], p < 0.001), fat (-41.70 g [SD 77.87 g], p < 0.001), percentage of fat (-4.79% [SD 11.38%], p = 0.001), and an increase in the percentage of protein (+ 2.72% [SD 7.10%], p = 0.002). A lower consumption of fat, especially of polyunsaturated fatty acids, was observed in the patients that achieved the nutritional recommendations and in the super-obese patients. CONCLUSION: The combination of NEP and BPD resulted in an improvement in the nutritional profile, with a reduction of fat and maintenance of the protein intake. PMID- 26262702 TI - [NUTRITIONAL STATUS OF UNIVERSITY STUDENTS FROM MEXICO IN RELATION WITH THEIR LIFESTYLE]. AB - INTRODUCTION: the change in lifestyle and nutrition has led to growing obesity; in Mexico there has been significant increase in its prevalence. The problem was thought limited to adult population, but it also affects children, adolescents and young adults. Obesity at an early stage of life, subsequently leads to obesity in adult life. Apparently few attempts with College students have being reported. OBJECTIVES: relate the effect of anthropometry and physical condition with dietary habits, physical activity and smoking addiction in students of a public university of Mexico, in order to establish a diagnosis of their nutritional status. METHODS: one hundred and seventy eight students, were measured obtaining: body weight, height, waist and hip circumference, body composition and blood pressure. A questionnaire to determine their physical activity was applied, a dietary assessment was also collected and socioeconomic status was established. Data were analyzed statistically by the method of least squares. RESULTS AND DISCUSSION: individuals classified as over-weighted, with obesity class 1 and class 2, accounted for 48.87% of the total population; more overweight and obesity was found in men compared with women, affecting negatively the value of blood pressure. This deteriorating health was attributable to poor eating habits: skipping breakfast and consumption of fast food. Smoking was revealed as a major risk factor since it adversely affected nutritional status. PMID- 26262703 TI - BODY ADIPOSITY INDEX AND ASSOCIATED FACTORS IN ADULTS: METHOD AND LOGISTICS OF A POPULATION-BASED STUDY. AB - INTRODUCTION: obesity is a public health problem that has increased considerably. Several techniques have been developed and used to measure the amount of body fat, or a combination of excess fat with some comorbidities. The Body Adiposity Index is a new method proposed to determine body fat and its validation is still limited. Methods and logistics of a population-based study reported in the literature are few, mainly multidiciplinas team. OBJECTIVE: the objective was to report the proceedings of a population-based study, the denouement is the index of adiposity in adults. DESIGN: the design of this study was cross-sectional, with a sample of 1085 adults aged 20-59 years living in the city of Vicosa, MG. A questionnaire was applied at home with sociodemographic, behavioral issues, health and level of physical activity. Then anthropometric and biochemical data were collected. The training for data collection involved the calibration of evaluators, being the correlation between the measurements checked by the intraclass correlation test and was adopted as the acceptable value of 0.60. RESULTS: it is noted that, with the exception of assessors 1, the triceps and subscapular skin folds, and the evaluator 4, in the pectoral skinfolds and suprailiac, all other measures reached acceptable cutoff point for agreement among evaluators. CONCLUSIONS: multidisciplinary research is important to understand the various factors that may be operating in health and disease process tool. Methodological and logistical aspects described in this study should be followed, which will lead to a steady decrease in research biases. PMID- 26262704 TI - [EFFECT OF A HEALTHY EATING AND PHYSICAL ACTIVITY INTERVENTION PROGRAM ON CHILHOOD OBESITY]. AB - BACKGROUND: interventions aiming to develop healthy lifestyle behaviours at early age could be an effective way of reducing childhood obesity. AIMS: to evaluate the effect of a dietary and physical activity intervention on reducing childhood obesity. METHODS: 312 students took part on this 5 month intervention study. The intervention included dietary talk delivered to children and their parents in addition to 45 minutes of daily physical activity modules. Nutritional status was assessed using the Obesity Task Force criteria. Changes in dietary behaviours and physical activity were assessed using questionnaires administrated to the parents. RESULTS: body mass index decreased significantly post intervention (-0.2 kg.m-2), however, this reduction was driven by boys (-0.3 kg.m-2). Similarly, waist circumference shows a significant reduction in boys (-0.4 cm) but not girls. Children with overweight or obesity shows greater reductions in obesity related traits, which were related to changes in dietary and physical activity post interventions. CONCLUSIONS: multidisciplinary interventions applied to children between 5 and 7 years old are effective on reducing body mass index and improving dietary and physical activity behaviours in overweight and obese children. PMID- 26262705 TI - PREVALENCE OF FACTORS ASSOCIATED TO METABOLIC SYNDROME IN A COHORT OF CHILDREN IN SOUTH BRAZIL. AB - INTRODUCTION: the Metabolic Syndrome is a group of disorders and it has gaining importance due to its association with the subsequent development of cardiovascular diseases. OBJECTIVES: to determine the prevalence of risk factors associated to the metabolic syndrome in children from a cohort in Southern Brazil. METHODS: a prospective cohort study with hospital screening of all births (2741) occurred from September 2002 to May 2003, monitoring a random sample of 30.0% at one, three and six months and eight years old. During the visit at the age of eight years, a questionnaire containing questions related to nutrition, physical activity and family history of chronic diseases. Also, weight, height and the waist circumference were measured. Descriptive and bivariate analyzes between independent variables and the outcome were performed. Results y discussion: from the 616 studied children, 51.3% were male, 70.3% had white, about half belonged to the economic class C, 20.5% were overweight and 16.9% were obese. There was high prevalence of family history for hypertension (81.5%), and was observed that 20.7% of the eutrophic children showed elevated waist circumference. CONCLUSION: the high prevalence of risk factors for the metabolic syndrome found in the studied children reinforces the importance of proper medical history including family history. It is suggested to include the measurement of waist circumference in routine pediatric care. PMID- 26262706 TI - THE ASSOCIATION BETWEEN PRE-PREGNANCY OBESITY AND WEIGHT GAIN IN PREGNANCY, WITH GROWTH DEVIATIONS IN NEWBORNS. AB - INTRODUCTION: obesity in pregnancy has been associated with increased morbidity for the mother and fetus. OBJECTIVE: to quantify the association between obesity in pregnancy with growth deviations of their newborn infants. METHODS: a study of non-matched cases and controls was performed based on the Nuevo Civil Hospital of Guadalajara "Dr. Juan I Menchaca" 2012-2013. The dependent variables were the newborn being either large (LGA) or small for gestational age (SGA), and the independent variable was pre-pregnancy obesity. Gynecoobstetric and socioeconomic data were collected. The association between the dependent and independent variables was assessed with logistic regression. RESULTS: one-hundred and forty three mother-child dyads were studied with growth deviations of their newborn infants, and 137 mother-child dyads without growth deviations were studied. The age of the patients was 24.7 +/- 6.3 vs. 24.0 +/- 6.0 years, and the gestational age was 38 +/- 1.2 vs. 38 +/- 1.5. Factors associated with growth deviations were pre-pregnancy obesity (OR 2.65, 95% CI 1.29- 5.44), elevated weight gain during pregnancy (OR 1.98, 95% CI 1.04-3.76) and disease during pregnancy (OR 2.62, 95% CI 1.05-6.76). A multivariate model with the dependent variable LGA and associated covariates showed that pre-pregnancy obesity and high gestational weight gain were predictors of LGA (OR 2.43, 95% CI 1.10-5.40) and (OR 3.31, 95% CI 1.83-5.96). CONCLUSIONS: in a population of young women with scarce economic resources, pre-pregnancy obesity and high weight gain during pregnancy were predictors of LGA. PMID- 26262707 TI - FOOD CONSUMPTION PATTERNS DURING PREGNANCY: A LONGITUDINAL STUDY IN A REGION OF THE NORTH EAST OF BRAZIL. AB - INTRODUCTION: the nutritional panorama in Brazil indicates that the dietary patterns of the population is characterized by the increasing inclusion of saturated and trans fats, sodium, sugars, soft drinks. This epidemiological and nutritional challenges reflects in the patterns of illness and death. OBJECTIVE: this study aims to identify patterns of food consumption and dietary changes in the first and third trimester of pregnancy. METHODOLOGY: this is a prospective cohort study involving 185 pregnant women in the State of Bahia, from 2012 to 2013. We used a food frequency questionnaire to assess dietary intakes. To identify the dietary pattern, the principal components factor analysis was adopted. We used the Pearson correlation test to identify the correlation between the patterns extracted in each trimester. RESULTS: four patterns of food consumption during pregnancy were identified. We observed changes in the eating patterns over the trimesters evaluated, especially for the food groups of fruit, coffee, fats, fried snacks, sugar and sweets. DISCUSSION: these dietary changes throughout the pregnancy accompany the physiological changes of each period of the pregnancy. In the first trimester, symptoms of nausea and vomiting are common, whereas in the same period cravings is reported, which may justify the consumption of a larger quantity of food deemed unhealthy. CONCLUSION: it was observed that there were changes in the adoption of dietary pattern throughout the evaluated trimesters of pregnancy, especially for the groups of fruit, coffee, fats, fried snacks and sugar and sweets. PMID- 26262708 TI - AMINO ACID LEVELS IN CHILDREN WITH CELIAC DISEASE. AB - BACKGROUND & AIM: plasma amino acid levels may show differences in regard to physiological changes, diet and diseases. The aim of the study is to measure the amino acid levels in children with celiac disease and compare them with the controls. MATERIAL AND METHODS: sixty-two children with classic celiac disease and 62 age and sex matched healthy control were enrolled in this study. Plasma amino acid levels of the children were measured by using tandem mass spectrometry. RESULTS: celiac children had significant lower plasma levels of citrulline, glutamine and cystine than control (p. PMID- 26262709 TI - [CHILD'S LIFESTYLE BEHAVIOURS RELATING TO WEIGHT AND MATERNAL SELF-EFFICACY IN MANAGING THEM]. AB - INTRODUCTION: parenting represents challenges. Mothers of overweight (OW) - obesity (OB) children face their children's lifestyle behaviors related to body weight. OBJECTIVES: 1) To assess the reliability of The Lifestyle Behaviour Checklist (LBC) in Spanish, 2) To evaluate the children's lifestyle behaviour that represent for the mother a problem for managing (PB) and self-efficacy (SE) to manage them in mothers of children with and without OW-OB and 3) To verify the differences between groups. METHODS: participated 367 dyads (mother / child). Mothers answered the LBC with two scales, problems behaviour scale (PBS) and self efficacy to managing them scale (SMS). The dyads' weight and size were measured. Cronbach's alpha coefficient, descriptive statistics and ANOVA were calculated. RESULTS: Cronbach's alpha for PBS was 0.86 and 0.96 for SMS. Watches too much television was the greatest problem in managing for mothers of children with and without OW-OB (F = .232, p = .630). The mothers of children with OW-OB had lower self-efficacy compared to mothers of children without OW-OB (F = 14,155, p = .001). The mothers of children with OW-OB perceived more PB (Mean = 55.40) and less SE compared to mothers of children without OW-OB (F = 15.45, p. PMID- 26262710 TI - [COMPARISON OF PSYCHOMOTOR DEVELOPMENT IN PRESCHOOL CHILEAN NORMAL WEIGHT VERSUS OVERWEIGHT/OBESITY]. AB - OBJECTIVE: to compare the DSM Nutritional distributed in three states: normal, overweight and obese. SUBJECTS AND METHODS: test DSM "TEPSI" 58 children (intentional sample) from a total of 150, 4 to 4.5 years, which were divided into 3 groups was applied: normal weight (n = 28); overweight (n = 18) and obese (n = 12). Weight and height were measured using a SECA scale and a bevel wall (methodology Frankfurt). Nutritional assessment was performed by BMI / age as proposed by the Center for Disease Control (CDC). Comparisons were made using analysis of variance, Tukey test and Kruskal-Wallis test. Box plots were used. The significance level was used in all cases alpha <= 0,05. RESULTS: preschool overweight and obese studied showed a driving profile classified as inferior and much lower, respectively, when they were compared with the normal weight group of preschoolers. CONCLUSIONS: overweight/obesity is a factor in the development of motor skills in preschool negatively 4 years old. PMID- 26262711 TI - [SHORT TERM EFFECTS ON LIPID PROFILE AND GLYCAEMIA OF A LOW-FAT VEGETARIAN DIET]. AB - INTRODUCTION: vegetarian diets have been associated with lower risk of cardiovascular disease and a more favourable lipid profile in vegetarians who follow these diets for a long term period in observational studies, but the short term effects of vegetarian diets are less known. OBJECTIVE: our objective was to analyze the short-term effects of a low-fat vegetarian diet on lipid profile and fasting glucose in previously non-vegetarian subjects from a Mediterranean population. METHODS: we carried out a nutritional intervention study in 159 volunteers (42 men and 117 women). A whole lacto-vegetarian diet low in fat (20%) was administered. A full daily menu was provided for 15 days under strict interned conditions. Fasting blood samples were obtained before and after dietary intervention and total cholesterol, HDL-C, LDL-C, triglycerides and fasting glucose were determined. Multivariate models for repeated measures were used. RESULTS: after dietary intervention, we detected statistically significant reductions in total cholesterol (-17.54 +/- 37.14 mg/dl), LDL-C (-9.33 +/- 34.29 mg/dl), HDL-C (-5.32 +/- 12.16 mg/dl), and triglycerides (-18.92 +/- 50.50 mg/dl). These reductions remained statistically significant after adjustment for sex and age. Significant weight changes were also detected. The additional adjustment for changes in body mass index (BMI) attenued the significance of the decrease in triglycerides (P = 0.067). CONCLUSION: a lacto-vegetarian diet low in fat, produces favourable and significant decreases in total cholesterol, LDL-C (independent of weight loss) and triglycerides (mediated by weight loss). This intervention also produced an expected decrease in HDL-C due to its reduced fat content. PMID- 26262712 TI - FISH OIL AND VITAMIN E CHANGE LIPID PROFILES AND ANTI-LDL-ANTIBODIES IN TWO DIFFERENT ETHNIC GROUPS OF WOMEN TRANSITIONING THROUGH MENOPAUSE. AB - BACKGROUND: studies have investigated the relationship between the transition through menopause and cardiovascular diseases. White population, generally, have lower levels of traditional coronary heart risk factors, particularly dyslipidemia, hypertension, obesity, and diabetes, and lower rates of coronary heart disease mortality, than black population. Furthermore many studies have shown the cardioprotective and anti-inflammatory effects of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid) of marine origin. The aim of this study was to investigate the effect of omega-3 supplementation, combined or not with vitamin E, on oxidative biomarkers and lipid profiles in nonwhite and white women with dyslipidemia transitioning through menopause. METHODS: a randomized, double-blind, placebo-controlled trial was conducted. Seventy-four eligible women were assigned to receive: fish oil, fish oil plus vitamin E and placebo for three months. At baseline, 45 and 90 days blood sample for biochemical variables and biomarkers of oxidative stress were taken. Socioeconomic and lifestyle variables were collected with standardized questionnaires. RESULTS: after 90 days the fish oil plus vitamin E treated group had a significant decrease in total cholesterol and LDL-C. Furthermore, there was a decrease in anti- LDL- autoantibodies after 45 days. Plasma TBARS concentrations were increased after 90 days in the group receiving only fish oil when compared to the placebo and fish oil-vitamin E groups. All of the effects observed were independent of ethnic group. CONCLUSION: supplementation with fish oil and vitamin E reduced total cholesterol and LDL-C, but had opposite effects on oxidative stress compared to supplementation with fish oil alone. PMID- 26262713 TI - ROLE OF RS9939609 FTO GENE VARIANT IN WEIGHT LOSS, INSULIN RESISTANCE AND METABOLIC PARAMETERS AFTER A HIGH MONOUNSATURATED VS A HIGH POLYUNSATURATED FAT HYPOCALORIC DIETS. AB - INTRODUCTION: common polymorphisms (rs9939609) of the fat mass and obesity associated gene (FTO) have been linked to obesity. OBJECTIVES: our aim was to investigate the role of this polymorphism on insulin resistance, metabolic changes and weight loss secondary to a high monounsaturated fat vs a high polyunsaturated fat hypocaloric diets. MATERIAL AND METHODS: a sample of 233 obese subjects was enrolled in a prospective way. In the basal visit, patients were randomly allocated during 3 months to; Diet M (high monounsaturated fat hypocaloric diet) or Diet P (high polyunsaturated fat hypocaloric diet). RESULTS: after treatment with two diets and in both genotypes, weight, fat mass and waist circumference decreased. Lower levels of body mass index (BMI), weight and fat mass were detected after Diet P in A allele carriers than TT genotype subjects. With the diet type P and in both genotypes (TT and AT + AA), total cholesterol levels (-15.3 + 35.1 mg/dl vs -11.6 + 32.1 mg/dl: p > 0.05) and LDL cholesterol levels (-11.5 + 34.1 mg/dl vs -8.5 + 30.1 mg/dl: p > 0.05) decreased. In A allele carriers a significant decreased was detected in insulin levels (-2.8 + 2.1 UI/L vs -1.3 + 8.0 UI/L: p < 0.05) and HOMA index (-1.0 + 1.3 vs -0.2 + 2.1: p > 0.05), too. With the diet M and in both genotype groups, leptin levels (-8.0 + 17.1 ng/ ml vs -4.9 + 18.7 ng/ml: p > 0.05) decreased. Conclusiones: metabolic improvement secondary to weight loss was better in A carriers with a high polyunsaturated fat hypocaloric diet. PMID- 26262714 TI - OBESITY PHENOTYPES IN URBAN MIDDLE-CLASS COHORTS; THE PRIT-LINDAVISTA MERGING EVIDENCE IN MEXICO: THE OPUS PRIME STUDY. AB - BACKGROUND AND AIMS: even though overweight and obesity (O/O) are stated diseases, there is still a claim for a so-called "healthy obese" phenotype. Only few reports have explored the presence of different metabolic phenotypes along the body mass index (BMI) range and their corresponding associations to cardiovascular risks. METHODS: as of BMI, and according to the presence of metabolic syndrome (MS) features (waist circumference, blood pressure, fasting glycemia, and lipid profile), phenotypes were determined. Cardiovascular risk was estimated with atherogenic quotients: total cholesterol/ HDL-c, LDL-c/HDL-c and the triglycerides (TG)/HDL-c index. RESULTS: in 8 405 mexican adults, 36% lean, 43% overweighed and 21% obese, nine phenotypes were identified: for each weight category there were subjects with normal metabolism (none MS factors), intermediate (<= 2) and dysmetabolic (>= 3). Only 10.8% of O/O had normal metabolism, and 5.8% of the lean persons were dysmetabolic. Atherogenic risk was higher in dysmetabolic obese persons, but the risk was high among all dysmetabolic people, independently of the weight status. TG/HDL-c showed the same trend. CONCLUSIONS: elevated cardiometabolic risk derives from the high prevalence of O/O. A great proportion of non-obese people have intermediate dysmetabolism. A genetic predisposition to obesity, insulin resistance, diabetes and dyslipidemia in Mexican population is blended to an unhealthy lifestyle, yielding to a catastrophic epidemic of diabetes, and cardiovascular diseases. PMID- 26262715 TI - MALNUTRITION IN PATIENTS WITH GASTROINTESTINAL CANCER: EFFECTIVENESS OF DIFFERENT DIAGNOSTIC METHODS. AB - OBJECTIVE: to estimate the effectiveness of methods for identifying the risk and/or presence of malnutrition in individuals with gastrointestinal neoplasia. METHODS: participated 143 patients with gastrointestinal cancer, cared for in the Oncology Clinic Infirmary of "Hospital Amaral Carvalho" (Jau-SP). Excluded from the study were patients hospitalized in the intensive care unit, in a terminal state or those who had members amputated; those who had received blood transfusions during the last month; significant clinical bleeding; received endovenous albumin and uncontrolled infection. The nutritional status was classified according to the ratio between Real Weight and Habitual Weight, Body Mass Index, Nutritional Risk Index and Percent Adequacy. As the gold standard method the Scored Patient-Generated Subjective Global Assessment was used. The effectiveness of the methods for detecting the risk for or presence of malnutrition was evaluated. A ROC curve was constructed and its area (AUROC) was estimated. The areas were compared using z statistics. For each method the best cut-off point was established. RESULTS: of the patients, 74.1% presented an advanced stage of the disease, and 83.2% were undergoing chemotherapy treatment. All the methods showed adequate discriminatory capacity for detecting the risk of malnutrition and presence of malnutrition. The BMI was significantly better for detecting malnutrition than for the risk of malnutrition. The RW/HW was significantly better for detecting the risk of malnutrition than the other methods. The cut-off points were slightly lower than those recommended for the normative population for the methods RW/HW, NRI and Score %. For the BMI the cut off point was higher than the recommended for the normative population. CONCLUSION: the methods for evaluating nutritional status showed adequate discriminatory capacity for the risk of malnutrition and presence of malnutrition in patients with gastrointestinal cancer. PMID- 26262716 TI - PREVALENCE OF METABOLIC SYNDROME IN YOUNG MEXICANS: A SENSITIVITY ANALYSIS ON ITS COMPONENTS. AB - INTRODUCTION: obesity is a worldwide epidemic, and the high prevalence of diabetes type II (DM2) and cardiovascular disease (CVD) is in great part a consequence of that epidemic. Metabolic syndrome is a useful tool to estimate the risk of a young population to evolve to DM2 and CVD. OBJECTIVE: to estimate the MetS prevalence in young Mexicans, and to evaluate each parameter as an independent indicator through a sensitivity analysis. METHODS: the prevalence of MetS was estimated in 6 063 young of the Mexico City metropolitan area. A sensitivity analysis was conducted to estimate the performance of each one of the components of MetS, as an indicator of the presence of MetS itself. Five statistical of the sensitivity analysis were calculated for each MetS component and the other parameters included: sensitivity, specificity, positive predictive value or precision, negative predictive value, and accuracy. RESULTS: the prevalence of MetS in Mexican young population was estimated to be 13.4%. Waist circumference presented the highest sensitivity (96.8% women; 90.0% men), blood pressure presented the highest specificity for women (97.7%) and glucose for men (91.0%). When all the five statistical are considered triglycerides is the component with the highest values, showing a value of 75% or more in four of them. Differences by sex are detected for averages of all components of MetS in young without alterations. CONCLUSIONS: Mexican young are highly prone to acquire MetS: 71% have at least one and up to five MetS parameters altered, and 13.4% of them have MetS. From all the five components of MetS, waist circumference presented the highest sensitivity as a predictor of MetS, and triglycerides is the best parameter if a single factor is to be taken as sole predictor of MetS in Mexican young population, triglycerides is also the parameter with the highest accuracy. PMID- 26262717 TI - THE EVOLUTION OF HOME ENTERAL NUTRITION (HEN) IN POLAND DURING FIVE YEARS AFTER IMPLEMENTATION: A MULTICENTRE STUDY. AB - BACKGROUND: home enteral nutrition (HEN) is the best option for chronic. patients without the ability to swallow, but with intact digestive tract. Despite the increasing use of home enteral tube feeding (HETF), there is little published information about the types of patients receiving home enteral nutrition. The purpose of this paper to present the evolution of HETF. MATERIAL AND METHODS: the retrospective multicenter observational study was performed using questionnaires, which were distributed among the biggest Polish HEN centres. The study covered all patients treated between January, 2007 and January, 2014. RESULTS: in total 196 adult patients in 2008 (M:104. F: 92, mean age 58.1 [41-75]) and 2842 in 2013 (M: 1541, F: 1301, mean age 61.4 range: 1-91) were assessed. The number of patients grew significantly between 2008 and 2013 (p < 0.05), rising from 196 up to 2 842 (and 1 716 at the moment of study). The predominant primary disease was neurology in both time periods, but the profile switched from neurovascular to neurodegenerative (p > 0.05). Percutaneous endoscopic gastrostomy was the most common GI access ( > 60%), its use and the use of gastrostomies increased significantly since 2008 (p < 0.05). Although the reimbursement for HETF started in 2007, HEN centres expressed doubts about unclear rules for the qualification to HEN and its use. CONCLUSIONS: HETF is a safe, well-tolerated and cost effective procedure. The profile of patients and techniques may vary at the beginning, but becomes similar to other HETF countries relatively soon. The number of patients grows quickly, and that fact suggests that the prevalence of HETF is similar in all countries. PMID- 26262718 TI - EFFECT ON QUALITY OF LIFE AND HANDGRIP STRENGTH BY DYNAMOMETRY OF AN ENTERAL SPECIFIC SUPLEMENTS WITH BETA-HYDROXY-BETA-METHYLBUTYRATE AND VITAMIN D IN ELDERLY PATIENTS. AB - AIM: the aim of our study was to investigate the effect on strenght and quality of life of an enhanced specific enteral formula with HMBD and vitamin D in elderly patients. METHODS: we conducted an open-label study. General assessment of nutritional status included measurements of body weight, height, body mass index (kg/m2) and bioimpedance. Handgrrip strength was measured by dynamometry. QOL (quality of life) was assessed using the well validated SF 36 questonnaire. Albumin, prealbumin, transferrin and 25-OH vitamin D were measured. All these parameters were recorded at basal time and after 12 weeks of nutritional intervention. RESULTS: patients were divided in two groups by the median percentage of weight improvement (3.4%); group 1 (percentage of weight improvement < 3.4%) and group 2 (percentage of weight improvement > 3.4%). In group 1, patients showed an improvement in prealbumin and vitamin D levels. In group 2, patients showed an improvement of BMI, weight, fat mass, fat free mass, prealbumin, vitamin D levels, role physical domain of SF 36 , general health domain of SF 36 and handgrip strength. The volumetric consumption rates of the formula were higher in group 2 than group 1 (group 1: 1.25 + 0.78 units/day [1.81 +/-0.9 g per day of HMBD) vs. group 2: 1.86 + 0.82 units/day (2.79 +/-1.1 g per day of HMBD]). CONCLUSIONS: elderly patients with a previous weight loss and with a high consumption of a HMBD and vit D enhanced formula had a significant improvement in anthropometric, biochemical parameters, handgrip strength and quality of life. PMID- 26262719 TI - [GASTROSTOMY POSITIVELY AFFECTS NUTRITIONAL STATUS AND DIMINISHES HOSPITAL DAYS IN PATIENTS WITH INBORN ERRORS OF METABOLISM]. AB - INTRODUCTION: the nutrition management of patients with inborn errors of metabolism (IEM) requires the permanent use of elemental medical formulas whose organoleptic characteristics sometimes impede oral acceptance. In addition, these patients may have gastrointestinal disorders and require constant use of drugs, that often complicate treatment adherence, thereby committing their nutritional status and disease control. Gastrostomy is an alternative to facilitate feeding and treatment, but its use is controversial. OBJECTIVE: to compare nutrition status and length of hospitalizations before and after gastrostomy surgery in a group of IEM patients. METHODS: retrospective analysis of anthropometric data, number of hospitalizations due to metabolic decompensation and length in pediatric patients with IEM before and after gastrostomy. RESULTS: 16 children were analyzed, 40% with propionate disorders, 25% with abnormal urea cycle and 35% other IEM. After gastrostomy, the number of eutrophic patients increased from 6-56%, and malnutrition decreased from 94 to 44%. After gastrostomy inpatient hospital days significantly decrease from 425 to 131 (p = 0.011), admission numbers pre-gastrostomy decreased from 33 to 17, however this difference was not statistically significant. CONCLUSION: in this sample, gastrostomy improved nutritional status in 56% of EIM patients and significantly reduced hospital days caused by metabolic decompensation. PMID- 26262720 TI - ECONOMIC BURDEN OF HOME ARTIFICIAL NUTRITION IN THE HEALTH AREA OF SANTIAGO DE COMPOSTELA. AB - INTRODUCTION: home artificial nutrition (HAN) is a growing therapy, but the absence of obligatory registries complicates the calculation of its real economic burden. The aim of this study was to assess the state and economic impact of HAN in our health area. METHODS: an observational, prospective study was designed to calculate the cost of nutritional formulas and materials in patients who initiated HAN in the nutrition unit during a year. RESULTS: we included 573 new patients with HAN during the study period, 60% of whom were treated with oral supplements. The median daily cost of oral HAN was 3.65 (IQR 18.63) euros compared to a cost of 8.86 (IQR 20.02) euros for enteral-access HAN. The daily expenditure per 1 000 kcal of diet was higher for patients on oral HAN than for patients with tubes (5.13 vs. 4.52 euros, p < 0.001). The median cost of the complete HAN treatments during the study period was also calculated (186.60 euros and 531.99 euros for oral and tube HAN, respectively). The total estimated cost for all patients who initiated HAN in the study period was around one million euros. CONCLUSIONS: HAN represented an important economic burden in our health area, but the estimated daily cost of HAN was moderate, probably because of the high frequency of oral HAN, the adjusted treatments, and the centralized dispensation by the hospital pharmacy. PMID- 26262721 TI - [THE CASE OF ENTERAL NUTRITIONAL SUPPORT TUBE IN COLOMBIA: INSTITUTIONAL COORDINATION PROBLEMS]. AB - INTRODUCTION: this paper examines the case of prescription enteral nutritional support tube in Colombia, analyzed from the perspective of the Social Security System in Health, and explained as the result of a problem of institutional coordination. The role and incentives of different actors are identified and shown how the interaction of these discourages the use of enteral nutrition in cases where it is necessary, with corresponding clinical effect for the patient and increased cost for the system. METHODS: analysis of the effects it may have in clinical practice the problem of institutional coordination of regulators in the country, analyze their origin and the incentives and interests of the various stakeholders, prior synthesis of the relevant literature review. The search was conducted in the following databases: PubMed, Medline, and Embase ScienceDirect. CONCLUSIONS: the current situation of enteral nutritional support in Colombia is the result of a suboptimal equilibrium, resulting from a problem of institutional coordination that can only be solved when the agents to look beyond their local incentives, and nutritional support is a key component of hospital care and constitutes a means to the end: the health of the population served. PMID- 26262722 TI - FUNCTIONAL CHARACTERS EVALUATION OF BISCUITS SUBLIMATED WITH PURE PHYCOCYANIN ISOLATED FROM SPIRULINA AND SPIRULINA BIOMASS. AB - The aim of the present work is to study the effect of incorporation of biomass and phycocyanin extracts of Spirulina platensis growing in define media at large scales (300 liters, limited in nitrogen and high salinity) to traditional butter biscuits in order to increase general mental health as functional products, FPs). The FP were manufactured at a pilot scale formulated by adding algal biomass (0.3, 0.6 and 0.9%) and S. platensis phycocyanin (at 0.3%) to wheat flour and stored for one month at room temperature, protected from light and air. The approximate and nutrition composition of S. platensis biomass showed high quantity (% dry weight, dw.) of phycocyanin (13.51%, natural food colorant), tocopherols (0.43%), carotenoids (2.65%), vitamins C (1.25%), ?-6, ?-3 fatty acids, essential elements (Fe, Zn, Cr, Se, and others) and antioxidant compounds includes: total phenolic (1.73%), flavonoids (0.87%) and glutathione (0.245 mM). FPs showed a high oxidative stability during storage (30 days) periods (as assessed by antiradical scavenging activity of DPPH and TBA test), compared with that in untreated food products (control). Data of sensory evaluation revealed that FPs containing S. platensis biomass or algae extracts were significantly acceptable as control for main sensory characteristics (colour, odour/ aroma, flavor, texture, the global appreciation and overall acceptability). S. platensis FPs presented an accentuated green tonality, which increase with the quantity of added biomass. Thus, it could be concluded that functional biscuits had good sensory and nutritional profiles and can be developed as new niche food market. PMID- 26262723 TI - [HYPOTENSIVE EFFECT OF AN EXTRACT OF BIOACTIVE COMPOUNDS OF OLIVE LEAVES: PRELIMINARY CLINICAL STUDY]. AB - OBJECTIVE: to evaluate the possible hypotensive effect in pre-hypertensive and hypertensive subjects of an olive leaf extract (OLE) standardized to 15% (w/w) in oleoeuropein, and with a 10% (w/w) mean content of triterpenic acids and 1% (w/w) in hydroxytirosol. Moreover, the possible effects on the blood antioxidant status and lipid profile have been also evaluated. MATERIALS AND METHODS: this interventional study has been performed in human volunteers, to whom 1 600 mg OLE/days, was administered. The analyzed parameters at the beginning and end of the study were diastolic and systolic pressure, delay in the LDL-cholesterol oxidation "lag time" and blood levels of nitric oxide (NO), malonic dialdehyde (MDA), antioxidant capacity (AOC) lipid profile, glucose, transaminases and creatinine. RESULTS: a decrease in the diastolic and systolic pressure, and an increase in the NO values all statistically significant (CHO) for all volunteers, was found. In volunteers with higher systolic pressure their levels were also significantly diminished after the intervention trial (P = 0,002). The LDL lag time increased significantly (P = 0,047). Additionally, in all volunteers CHO levels were significantly decreased, and those of LDL cholesterol, triglycerides (TG) and the CHO/HDL cholesterol ratio were diminished with a tendency to the significance (P = 0,076; P = 0,059; P = 0,056; respectively). CONCLUSIONS: this preliminary study reports by the first time the positive influence of the OLE assayed in the regulation of the hypertension, LDL lag time and blood lipid profile. Therefore, further studies are of great interest. PMID- 26262724 TI - PROTEIN NEEDS OF CRITICALLY ILL PATIENTS RECEIVING PARENTERAL NUTRITION. AB - BACKGROUND: assess whether the current protein intake recommendations may improve the biochemical parameters of critical patients receiving parenteral nutrition. METHODS: longitudinal study with three evaluations made (during the first 72 hours, on the 7th and the 14th days of PN). The following tests were applied: albumin, C-reactive protein, prealbumin, total cholesterol, HDL, triglycerides, lymphocytes, and glutathione peroxidase. The severity was determined by SOFA. The statistical analysis included the Spearman and Mann-Whitney tests, as well as ANOVA (analysis of variance). RESULTS: among the 53 patients evaluated, 20 (37.74%) died. The mean calorie was 24.68 +/- 9.78 kcal/kg (beginning of PN), 26.49 +/- 8.89 kcal/kg (3rd to 7th days of PN), and 30.9 +/- 12.19 kcal/kg (7th to 14th days of PN). The mean protein was 1.19 +/- 0.44 g/kcal/kg (first 72 hours of PN), 1.29 +/- 0.44 g/kcal/kg (3rd to 7th days of PN) and 1.49 +/- 0.69 g/kcal/kg (7th to 14th days of PN). Prealbumin, albumin, total cholesterol and HDL were below the reference values, while the CRP levels were high. Throughout the three evaluation times, there was no a significant improvement on the levels of laboratory examinations. A strong and negative correlation was found between SOFA and prealbumin (r = -0.64, p = 0.05). CONCLUSIONS: the protein offer, according to the traditional recommendations, was not enough to improve the biochemical parameters of critical patients undergoing parenteral nutrition. PMID- 26262725 TI - METABOLIC EFFECTS OF Beta-GLUCANS (SACCHAROMYCES CEREVISAE) PER OS ADMINISTRATION IN RATS WITH STREPTOZOTOCIN-INDUCED DIABETES. AB - INTRODUCTION: beta-glucans (BG) derived from plant tissues are reported to show metabolic effects. In contrast, those fibers isolated from yeast seem to be more related to immune response modulation. Since diabetic individuals are more susceptible to exacerbation of inflammatory signs, the ingestion of fibers that could conjugate both metabolic and immune effects would be of great importance. OBJECTIVE: we investigated the effect of BG - Saccharomyses cerevisae - ingestion on glycemic and lipoprotein profile of diabetic rats. DESIGN: twenty-four adult Wistar rats were used, distributed into 4 groups in a design of entirely casualized delineation with a 2 x 2 factorial model (with and without diabetes; with and without BG). Diabetes Mellitus was induced by an intraperitoneal injection of 80mg/kg of strepzotocin. Thus, animals with fasting glycemia of over 250 mg/dl were considered diabetic. Forty-eight hours after induction, the rats received daily doses of 30 mg/kg of BG or saline solution by gavage during 28 days. RESULTS AND DISCUSSION: the Groups with DM presented a higher glycemic index and lower C peptide levels than the control groups, in addition to lower weight gain and higher ration consumption, water ingestion and urinary volume. Total cholesterol levels (CT), LDL-C + VLDL-C, plasma triacylglycerides (TAG) and alanine aminotransferase (ALT) were also higher in the diabetic animals (p < 0.05), and there were no alterations in the HDL-C levels. The ingestion of BG reduced blood glucose concentrations (30%), TAG (32%) and ALT (41%) (p < 0.05). No histopathological hepatic alterations were observed in any of the groups. Furthermore, the diabetic animals present increase in villous:crypt ratio (V:C) in the duodenum, without interference of BG. No alterations in the carcass were observed between the groups. CONCLUSION: it was concluded that the use of BG significantly reduced the glycemic, TAG and ALT levels, showing its therapeutic potential. PMID- 26262726 TI - HEPATIC FATTY ACID PROFILE OF RATS FED A TRIHEPTANOIN-BASED KETOGENIC DIET. AB - OBJECTIVE: the aim of this study was to evaluate the influence of consumption of a ketogenic diet supplemented with triheptanoin, a medium-chain anaplerotic triacylglycerol, on the liver fatty acid profile of Wistar rats. METHODS: three groups of male Wistar rats (n = 10) were submitted to an AIN-93 control diet, a triheptanoin- based ketogenic diet, or a soybean oil-based ketogenic diet for 60 days. Excised livers were subjected to lipid extraction and methylation to obtain fatty acids methyl esters, which were subjected to gas chromatography- mass spectrometry. RESULTS AND DISCUSSION: compared to the rats fed the control diet, those fed ketogenic diets showed a significant reduction in the concentrations of 9-hexadecenoic and 9-octadecenoic acids, whereas those fed triheptanoin showed increased levels of octadecanoic acid. CONCLUSION: changes in the liver fatty acid profiles of the rats fed a triheptanoin-based or a soybean oil-based ketogenic diet did not seem to be related to the dietary fat source, but rather to the characteristics of the ketogenic diets themselves. PMID- 26262727 TI - [CONSISTENCY OF MINI NUTRITIONAL ASSESSMENT TO IDENTIFY SARCOPENIA IN OLDER ADULTS IN NURSING HOMES IN BOGOTA, COLOMBIA]. AB - INTRODUCTION: malnutrition and sarcopenia, which have similar physiological mechanisms and are both responsible for adverse health outcomes, are highly prevalent in the elderly. OBJECTIVES: to measure the consistency of the MNA with the diagnosis of sarcopenia in older adults. METHODS: cross-sectional study of consistency in four nursing homes in Bogota. The nutritional screening and nutritional assessment were made with the Mini Nutritional Assessment in its long form; the diagnosis of sarcopenia was done with the algorithm and the breakpoints of the European Consensus (EWGSOP). STATISTICAL ANALYSIS: Pearson Chi2, Mann Whitney and consistency by Cohen's kappa coefficient. RESULTS: we included 108 patients, 62% women, mean age 80.4 years (SD 7.7). The prevalence of sarcopenia, malnutrition and risk of malnutrition were 38.9%, 33.3% and 2.8% respectively. The concordance of the MNA with the diagnosis of sarcopenia was slight (kappa 0.1908 95% CI 0.0025 to 0.3791, p < 0.05) CONCLUSION: MNA shows mild concordance to identify sarcopenia, suggesting that it is not an appropriate tool for the diagnosis of sarcopenia in older institutionalized adults. PMID- 26262728 TI - GASTRIC CANCER AND ASSOCIATED FACTORS IN HOSPITALIZED PATIENTS. AB - BACKGROUND: despite the decline in its incidence and mortality rate, gastric cancer continues to be the 4th most common tumor and the 2nd cause of death in the world. OBJECTIVE(S): to analyze the factors associated with gastric cancer in hospitalized patients. METHOD: Transversal study of case series type made at Recife hospitals. The data were obtained from a questionnaire adapted from a previously validated model, which consists of socioeconomic factors, eating habits, lifestyle, family history of cancer, infection by H. pylori and anthropometric data. RESULTS: among 33 patients, there was a slight prevalence of women aged >= 60, from rural areas, with low education and income levels. According to IMC, 57.6% were eutrophics and 69.7% at nutritional risk when used % PP. It was found that 42.4% did not undergo any examination for H. pylori, 48.5% had a genetic predisposition, 75.8% were sedentary, 60.6% smokers and former smokers, 51.5% addicted to alcohol and 36.4% were overweight patients. There was frequent consumption of salty foods, fried foods, and low intake of fruits, foods containing nitrates / nitrites and inadequate food storage. CONCLUSION: low socioeconomic status, physical inactivity and inappropriate diet patterns were prevalent factors for gastric cancer in the treated group. PMID- 26262729 TI - [INFLUENCE OF REPRODUCTIVE FACTORS, BREASTFEEDING AND OBESITY ON THE RISK OF BREAST CANCER IN MEXICAN WOMEN]. AB - Breast cancer (BC) is considered a global public health problem, and is the most frequently type diagnosed in Mexican women. Therefore, it is important to study the risk factors associated to this neoplasia in order to establish prevention strategies. The aim of this study was to evaluate the effect of hormonal contraceptives and hormone therapy (HT) use and period of use, breastfeeding practice, abdominal obesity and weight gain in adulthood, on the risk of BC in adult women from Northwest Mexico. This was a case-control study that included 162 women (81 cases and 81 controls). A sociodemographic and health questionnaire, and a survey history of body weight were applied to participants. Measurements of body weight, height and waist circumference were performed. To assess the association between BC risk and exposing factors, a multivariate logistic regression model was used. Average age of cases and controls were 51.8 +/- 11.7 and 51.4 +/- 11.3 years, respectively. No significant association was found between the use and period of use of hormonal contraceptives and HT with the risk of BC. The practice of breastfeeding (OR=0.34, 95%CI: 0.12- 0.92) and the time of exclusive breastfeeding (OR=0.64, 95%CI: 0.42-0.97; crude) were protective against the risk of BC. Abdominal obesity (OR=0.93, 95%CI: 0.90-0.97) and weight gain in early adulthood (OR=0.90, 95%CI: 0.85-0.95) were inversely associated to the risk of BC. In conclusion, the practice of breastfeeding may help prevent BC in Mexican women. PMID- 26262730 TI - [INFLUENCE OF BODY COMPOSITION ON VERTICAL JUMP PERFORMANCE ACCORDING WITH THE AGE AND THE PLAYING POSITION IN FOOTBALL PLAYERS]. AB - INTRODUCTION: body composition and vertical jump are two factors in the multifactorial approach to talent identification in soccer with implication on performance monitorization and injury rehabilitation. The aim of this study was to describe the anthropometric attributes and vertical jump performance in young soccer players based on their playing position. METHODS: four hundred and thirty four young soccer players from 7 to 25 years (13.4 +/- 3.45 yrs; 156 +/- 17 cm; 47.9 +/- 15.4 kg), who trained 3 days/week for 1.5 hours/ day, took part in the study. All were split up based on their age or soccer category (U9, U11, U13, U15, U17, U25) and playing position (goalkeeper, defenders, midfielders and forwards). Then, body composition was measure using the anthropometric method and vertical jump performance was analysed by three vertical jump test Squat Jump (SJ), Counter-movement Jump (CMJ) and Abalakov Jump (CMJA). RESULTS: significant differences among playing positions were mainly detected in categories U13, U15 and U25. Goalkeepers from U13 category reported a significantly higher fat free mass, appendicular lean body mass, area of the thigh and area of the calf (P < 0.05). While, defenders from U25 category showed a significantly greater vertical jump performance compared to midfielders for SJ, midfielders and forwards for CMJ and all playing position for CMJA (P < 0.05). CONCLUSIONS: in addition to biological age and muscle mass development, playing position should be taken into consideration as a relevant variable in the utilization of body composition and vertical jump performance as talent detection factors. PMID- 26262731 TI - [PREVALENCE OF DEHYDRATION BEFORE TRAINING IN PROFESIONAL CHILEAN SOCCER PLAYERS]. AB - INTRODUCTION: there is a lack of studies concerning hydration status before training in professional soccer player. PURPOSE: to describe hydration status before regular training practices in professional soccer players. METHODS: a total of 156 male soccer players (age 25.4 +/- 5.2 y) from six professional Chilean clubs were included. No hydration or food intake recommendations were made before experiment, with the aim to assess hydration status under athlete's regular "real" conditions. Body mass, height and urine specific gravity (USG) measurements were performed before training practices. RESULTS: 98% of athletes showed dehydration (between moderate and severe) before regular training practices. DISCUSSION: dehydration is the most prevalent hydration status in professional Chilean soccer players before training, which may negatively affect athlete's performance and may increase their risk of heat-related injuries. PMID- 26262732 TI - [CRITERION-RELATED VALIDITY OF SIT-AND-REACH TEST AS A MEASURE OF HAMSTRING EXTENSIBILITY IN OLDER WOMEN]. AB - INTRODUCTION: lumbo-sacral posture and the sit-andreach score have been proposed as measures of hamstring extensibility. However, the validity is influenced by sample characteristics. OBJECTIVE: to determine the validity of lumbo-horizontal angle and score in the sit-and-reach test as measures of hamstring extensibility in older women. METHOD: a hundred and twenty older women performed the straight leg raise test with both leg, and the sit-and-reach test (SR) in a random order. For the sitand- reach test, the score and the lumbo-sacral posture in bending (lumbo-horizontal angle, L-Hfx) were measured. RESULTS AND DISCUSSION: the mean values of straight leg raise in left and right leg were 81.70 +/- 13.83o and 82.10 +/- 14.36o, respectively. The mean value of EPR of both legs was 81.90 +/- 12.70o. The mean values of SR score and L-Hfx were -1.54 +/- 8.09 cm and 91.08o +/- 9.32o, respectively. The correlation values between the mean straight leg raise test with respect to lumbo-sacral posture and SR score were moderate (L Hfx: r = -0.72, p < 0.01; SR: r = 0.70, p < 0.01). Both variables independently explained about 50% of the variance (L-Hfx: R2 = 0.52, p < 0,001; SR: R2 = 0.49, p < 0,001). CONCLUSIONS: the validity of lumbo-sacral posture in bending as measure of hamstring muscle extensibility on older women is moderate, with similar values than SR score. PMID- 26262733 TI - STRAIGHT-A STUDENTS DISLIKE PHYSICAL EDUCATION IN ADOLESCENCE: MYTH OR TRUTH? THE AVENA, AFINOS AND UP&DOWN STUDIES. AB - OBJECTIVE: to examine if those adolescents who dislike physical education classes get better results on academic and cognitive performance than their peers. METHODS: participants included 4 226 adolescents from the AVENA, AFINOS and UP&DOWN studies. Physical education enjoyment was assessed with a 7-point Likert scale. Cognitive performance in the AVENA study was assessed using the Spanish version of the SRA Test of Educational Ability. Academic performance in the AFINOS and UP&DOWN studies was assessed through Mathematics and Language grades and the average of both subjects. RESULTS: in the AVENA study we found differences in verbal ability among girls who dislike physical education and their peers (P = 0.033). In the AFINOS study, boys who dislike physical education had higher scores in Language than their peers (P = 0.024). In the UP&DOWN study girls who disliked physical education had higher scores in Language and in the average of Language and Mathematics than their peers (P < 0.001). CONCLUSION: in the AVENA and AFINOS studies adolescents who disliked physical education had similar results in cognitive and academic performance than their peers, but in the UP&DOWN study girls who disliked physical education showed higher results in academic performance than their peers. PMID- 26262734 TI - [EVALUATION OF GYM USERS' DIET WITH MUSCLE DYSMORPHIA (BIGOREXIA)]. AB - OBJECTIVE: it is an innovative study where has been analyzed the diet among gym users with Muscle Dysmorphia (MD) of gyms in the province of Alicante. METHODOLOGY: it have been analyzed 141 male gymnasts of several gyms of Alicante (urban area of southeastern Spanish) aged between 18-45 years old, who purpose increasing their muscle mass. Were considered BMI (kg/m2) and 24 hour diet. And it has been determined whether or not suffer MD trough Muscle Appearance Satisfaction Scale. RESULTS: the sample consisted of 141 men, of whom 45 are MD and 96 are not according to Muscle Appearance Satisfaction. Protein intake was calculated and was greater than 1.5 g/kg/day in patients without MD and greater than 2 g/kg/day in the MD group. Analyzing the other nutrients, results show that the proportion of carbohydrates and fats and their percentages by degree of instauration are within the recommendations except cholesterol which exceeds and the amount of dietary fiber that is slightly lower. In relation to micronutrients are within the recommendations in all cases except iodine which is slightly lower in MD. CONCLUSION: individuals with MD do a balanced energy and adequate carbohydrate and fat diet, however protein intake values exceed the limits proposed according to the scientific evidence for muscle mass development in strength sports. PMID- 26262735 TI - [PHYSICAL EDUCATION CLASSES ONLY IMPROVE CARDIORESPIRATORY FITNESS OF STUDENTS WITH LOWER PHYSICAL FITNESS: A CONTROLLED INTERVENTION STUDY]. AB - INTRODUCTION: physical education teachers are required to carry out intervention programs in order to improve students' cardiorespiratory fitness levels. Nevertheless, due to the low academic load, such programs may not improve cardiorespiratory fitness of students with higher baseline levels. OBJECTIVES: the purpose of the present study was to compare the effect of a physical fitness program conducted during the two physical education classes on the cardiorespiratory fitness depending on the students' physical fitness baseline levels. METHODS: a sample of 71 primary school students and 107 secondary school students was randomly assigned (by natural groups) to the control and experimental groups. During physical education classes, experimental students performed a physical fitness program. RESULTS: the analysis of variance results showed that the experimental students with lower physical fitness levels improved statistically significantly their cardiorespiratory fitness comparing with control students (p < 0.01). However, no statistically significant differences between the experimental students with higher levels and control students were found (p > 0.05). CONCLUSIONS: during physical education classes, only students with lower physical fitness levels seem to improve cardiorespiratory fitness. On the other hand, students with higher physical fitness levels do not benefit from these physical education-based programs. Therefore, in order to improve cardiorespiratory fitness of all young people, it seems necessary to increase the academic load of the physical education subject. PMID- 26262736 TI - [RELATION BETWEEN THE BODY COMPOSITION AND THE SPORTS PRACTICE IN TEENAGERS]. AB - INTRODUCTION: knowing precisely body composition is important in assessing the nutritional status of adolescents in order to evaluate how it affects the sport practice in this group. OBJECTIVES: to evaluate the influence of regular physical exercise in a group of adolescents in their body composition. METHODOLOGY: 77 male adolescents between 12 and 13 years were evaluated. Weight, height, triceps skinfold (PCT), wrist perimeter, the relaxed arm and umbilical waist were evaluated. The body fat percentage (% BF) was estimated using different equations (Siri, Siri modified, Lohman, Johnston, Deurenberg BMI, body fat percentage from ICT). Electrical bioimpedance equipment was also used. RESULTS: no significant differences in BMI between the two groups were found. The prevalence of overweight and obesity varied by percentile tables used. Differences in the PCT and the percentage of body fat between groups were significants; it was higher in non-athletes (p < 0.05). No significant differences between the values of body fat were obtained by modified equations Siri, Lohman and bioimpedance, in none of the two groups studied. DISCUSSION: the % BF was higher in the group of non athletes, as well as the value of PCT to the same value of BMI. It was determined that the collective athlete got a better nutritional status than the non-athletic collective. Regardless of the method used, results should be interpreted with caution in assessing body composition of adolescents. PMID- 26262737 TI - ANTHROPOMETRIC CHARACTERISTICS AND PHYSICAL FITNESS LEVEL IN RELATION TO BODY WEIGHT STATUS IN CHILEAN PRESCHOOL CHILDREN. AB - The purpose of this study was to describe anthropometric and physical fitness characteristics of low-income Chilean preschool children and to examine whether weight status influences children's performance on fitness tests. A total of 434 preschool children (246 boys; 5.48 +/- 0.31 years) participated in our study. Anthropometry (weight, height, body mass index -BMI- and waist circumference) and fitness tests (handgrip strength test, standing long jump and 20 m sprint) were assessed by trained nutritionists and physical education teachers, respectively. Significant differences in anthropometry and fitness tests between boys and girls were found. The prevalence of overweight was higher in girls; in contrast to that of obesity. Compared to normal-weight children, overweight/obese boys and girls were heavier and had greater waist circumference (P < 0.001), were taller (P <= 0.002), and showed higher performance in handgrip strength (P <= 0.027) but not in standing long jump nor 20 m sprint (P >= 0.052). Screening physical fitness levels in overweight/obese preschool children could be an important tool in order to design an efficacy physical activity programme. PMID- 26262738 TI - UNDERNUTRITION, SERUM VITAMIN B12, FOLIC ACID AND DEPRESSIVE SYMPTOMS IN OLDER ADULTS. AB - BACKGROUND: the question on whether undernutrition remains linked to depressive symptoms, considering the effect of deficiencies of vitamin B12 and folate, is of practical relevance because they are potentially preventable and treatable. This study aims to evaluate whether undernutrition is linked to depressive symptoms, considering the effect of vitamin B12 and folate plasma levels. METHOD: a cross sectional study was conducted in a sample of 84 older adults living in care homes. Data about nutritional status using Mini-Nutritional Assessment, serum folic acid and Vitamin B12 levels, cognitive ability, functional dependency, symptoms and /or depressive behaviour was obtained. Depression symptoms were measured using the 20-item version of the Center for Epidemiologic Studies Depression scale. RESULTS: fifty three older adults were at depression risk (63.1%). Of those, 34% were at undernutrition risk. Although a high frequency of older adults with low plasma levels of vitamin B12 (42.9%) and lower levels of folic acid (5.9%) was found, no significant differences concerning the existence of depressive symptoms were found. In the multivariable analysis, an increase in depression risk was observed amongst participants nutritionally at risk OR = 3.47 (1.05-11.46), whereas having low levels of folic acid and Vitamins B12 were not associated with depression risk. CONCLUSION: amongst undernourished older adults, an increase in risk of depression was observed independently of folic acid and vitamin B12 status. These results highlight the need to implement preventive strategies, particularly directed at older adults living in care home. PMID- 26262739 TI - [ASSOCIATION BETWEEN STEVIA SWEETENER CONSUMPTION AND NUTRITIONAL STATUS IN UNIVERSITY STUDENTS]. AB - INTRODUCTION: stevia consumption has increased worlwide among the different age groups; however, studies regarding the association between stevia intake and nutritional status in adults are scarce. OBJECTIVE: to evaluate stevia intake in first year university students from five chilean cities (Santiago, Temuco, Vina del Mar, Concepcion and Antofagasta) controlling by nutritional status, socioeconomic level, gender and whether their undergraduate program belongs to the health sciences. MATERIALS AND METHODS: 486 first year university students belonging to 4 Chilean universities were evaluated. Each student completed a weekly food frequency questionnaire including food and beverages containing stevia. Selfreport of weight and height was requested. RESULTS: 69.8% of the students consumed stevia every week, the liquid form being the main contributor to the dietary stevia intake (81.2%). Only 1.4% of the students went over the Acceptable Daily Intake (ADI). Normal weight women show a higher stevia intake compared to those obese or overweight (p < 0.05). Finally, stevia consumption appears to be positively associated to normal weight in the first model (adjusted) (OR = 0.219; IC 95%: 0.13-0.35; p < 0.05) and second model (OR = 0.21; IC 95%: 0.13-0.35; p < 0.05). CONCLUSION: stevia consumption was positively associated with normal nutritional status in Chilean university students. PMID- 26262740 TI - FATTY ACID PROFILE OF TWO CURED MEAT PRODUCTS: DRY-CURED HAM AND CECINA. AB - INTRODUCTION AND OBJECTIVES: the aim of this study was to assess the fatty acid profile of two cured meat products of similar manufacturing processes and characteristics, dry-cured ham (JA) and cecina (CE), a type of dry-cured beef. The obtained results were discussed in terms of the effects that each singular fatty acid, when consumed, could have on human health. MATERIALS AND METHODS: for this purpose, 10 samples of 100 g of JA and CE were obtained in local food stores in Leon, Spain. Lipids were extracted and transesterified, then a gas chromatography-mass was used to analyze the samples. RESULTS AND DISCUSSION: results for fatty acid profiles for JA and CE showed significant differences (p < 0.01), with these values for main lipids fractions, saturated fatty acid (SFA), monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA), respectively: 42.86%, 43.27% and 13.87 for JA and 46.87%, 46.96% and 6.20% for CE. SFA and MUFA percentages were slightly higher in CE at the expense of PUFA, specifically in the n-6 series, where values of 11.06% in JA and 3.91% in CE were obtained. In both products, the most prevalent fatty acid was a monounsaturated fatty acid, oleic acid, with percentages of 37.28% in JA and 38.48% in CE. Other fatty acids with higher percentages, with respect to total fat, were two saturated fatty acids: palmitic acid, 20.63% in JA and 22.95% in CE, and stearic acid, 18.65% in JA and 17.14% in CE. PMID- 26262741 TI - [VARIATION ON SOMATOTYPE AND WAIST CIRCUMFERENCE IN A SAMPLE OF UNIVERSITY STUDENTS BETWEEN YEARS 2012 AND 2014 IN THE TEMUCO, CHILE]. AB - Objetive: to determine variation on somatotype and waist circumference (WC) in university students during a three-year follow-up. METHODS: a total sample of 36 first-year university students was recruited in 2012. Heath-Carter anthropometric somatotype and waist circumference were assessed in 2012 and 2014. RESULTS: male students showed mesomorph component (3.7-5.3-1.8) as dominant in 2012, while in 2014 endomorph and mesomorph components were equal (4.1-4.5-1.6). The somatotype in female students was dominated by endomorphic component in 2012 (5.4-4.6-1.7) and 2014 (5.3-3.2-1.6). Among somatotypes, for both, male and female students, only endomorphy showed statistically significant differences during the follow-up (p = 0,00). The endo-mesomorphic somatotype was dominant in men with 61.9% in 2012 and 38.1% in 2014. Women showed a higher percentage for meso-endomorphic somatotype with 60% in 2012 and 80% in 2014. In men, WC between 2014 and 2014 showed a statistically significant increment of 4.8% (p = 0,00). In women WC increased by 13.3% but no statistically difference was observed (p = 0,10). CONCLUSIONS: this study showed somatotypic change with tendency in increased endomorphy in both men and women. Despite WC values were similar to the national mean, cases with cardiometabolic risk increased during the follow-up period based on this measurement. PMID- 26262742 TI - [A SIMPLE AND RELIABLE TOOL FOR DETECTION OF NUTRITIONAL RISK IN HOSPITALIZED PATIENTS]. AB - INTRODUCTION: malnutrition in hospital associates with complications such a high rates of infections, increased length of stay, and increased economic costs. Hospitals require applying a simple and reliable tool for detection of nutritional risk. OBJECTIVE: to evaluate the agreement between a screening tool used in a hospital and both MUST and SGA tools to determine the prevalence of nutritional risk. METHODS: patients -with a hospitalization period less than 36 hours- were assessed with three nutritional screening tools. Kappa value was used to assess agreement between the tests; SGA was the gold standard. RESULTS: the study included 100 patients (F = 49, M = 51) with a mean age of 49 years. MUST presented a good agreement with the SGA (kappa = 0.55). CONCLUSIONS: MUST presents the highest agreement with the gold standard; therefore, it must be used to screen nutritional status of hospitalized patients due to its simplicity, reliability, and reproducibility. PMID- 26262743 TI - SCHOOL DIETARY HABITS AND INCIDENCE OF DENTAL CARIES. AB - INTRODUCTION: healthy dietary habits are considered to improve oral health and tooth quality. Caries treatment comprises tooth restoration with dental composites and sealants, almost all (> 90%) of which contain bisphenol A (BPA). Study hypotheses were: a) breakfast and oral hygiene habits are important factors in dental caries development; and b) dental caries treatment with epoxy-resins entails a risk of oral exposure to monomers migrating from the polymeric material. We evaluated caries in the teeth of a Spanish school population and determined the percentage treated with dental composites. OBJECTIVE: to relate consumption of breakfast components and oral hygiene habits to dental caries and determine the presence of sealants/composites as potential sources of BPA exposure. METHODS: subjects: 582 schoolchildren from Granada city (Southern Spain) aged 7 yrs; mean (SD) of 7.55 (0.64) yrs. RESULTS: caries was detected in 21.7% of their teeth. Mean breakfast quality index (BQI) score, based on nutritional questionnaires, was 5.18 (1.29). Breakfast with foods rich in simple sugars representing > 5% of total daily energy was consumed by 24% of the population and was significantly associated with caries frequency in binary logistic regression analysis. Biscuit consumption was reported by 35.8% and significantly associated with caries frequency. Breakfast intake of bakery products/ cereals and of dairy products showed a significant inverse association with caries frequency. No significant relationship was observed between caries and BQI score or oral hygiene factors. CONCLUSION: further research is required to elucidate the role of diet in caries and the associated risk of exposure to estrogenic xenobiotics such as BPA. PMID- 26262744 TI - [VALIDATION OF A COMPUTER PROGRAM FOR DETECTION OF MALNUTRITION HOSPITAL AND ANALYSIS OF HOSPITAL COSTS]. AB - BACKGROUND: one of the methods of diagnosis of malnutrition is serum albumin, for the simplicity of its determination and low cost. OBJECTIVES: the main objective is to validate and implement a computer program based on the determination of serum albumin, allowing early detection and treatment to malnourished or at risk of malnutrition patients, still another objective evaluation of costs by diagnosis-related groups. METHODS: the study design is cohort, dynamic and prospective, which are included hospital discharge from november 2012 until march 2014, being the study population of patients over age 14 who enter the various services of a Medical Surgical Hospital of the Granada's Hospital Complex Univesity, whose numbers are lower serum albumin 3.5 g/dL, for a total of 307 patients. RESULTS: of the 307 patients, 141 are malnourished (program sensitivity: 45.9%). 54.7% of patients were male and 45.3% female. The mean age of 65.68 years. The median length of stay is 16 days. 13.4% of patients have died. The average cost of GRD is ? 5 958.30 and said average cost after detecting malnutrition is ? 11 376.48. CONCLUSIONS: the algorithm that implements the software identifies nearly half of patients hospitalized malnourished. It is essential to record the diagnosis of malnutrition. PMID- 26262745 TI - [DEMOCOPHES SPAIN AND ITS CONTRIBUTION TO THE HARMONIZATION OF EUROPEAN HUMAN BIOMONITORING]. AB - Objetive: contributing to demonstrate of the feasibility of a coordinated action on human biomonitoring in Europe (DEMOCOPHES project) and demonstrate the utility of HBM studies to assess the influence of diet and lifestyle in environmental exposures. METHODS: the EU protocol was adapted to the national requirements. The quality controls defined herein were followed and special care was taken to ensure the comparability of the results among participating countries. RESULTS: the protocol adaptation did not shown significant difficulties. Only minor changes were applied, so the original design of the study was respected. 134 mother- child pairs were selected in one school in Anover de Tajo (Toledo) and three schools in Madrid. All volunteers donated a urine and hair sample and complete the epidemiological questionnaire. Significant differences were found in the participation rates between the sampling locations. DISCUSSION: standardization of all steps in a human biomonitoring study is essential for its harmonized development in Europe. The results has contributed to obtain for the first time comparable data about environmental exposure in the general population within 17 EU countries showing the differences associated with diet and lifestyles. The experiences and materials developed in the fieldwork could be applied to the design and implementation of HBM studies in the future. PMID- 26262746 TI - [BALANCED SCORECARD AS A MANAGEMENT TOOL IN CLINICAL NUTRITION]. AB - Nowadays, balanced scorecards have updated traditional management systems in the business sector. In this way, Kaplan and Norton propose performance measurement through several perspectives with a logical sequence: internal processes and learning impact client services, so that financial performance is affected. The aim of the present paper is to analyze the main characteristics of balanced scorecard when it is applied to non-for-profit companies and, specifically to the health sector in the clinical nutrition field. This model improves the economic vision of management with clinical indicators that represent healthcare professional's perspective. The balanced scorecard would allow a proper monitoring and tracking system for the main healthcare indicators. This contributes to a better control in comparison with standards that are associated with adequate quality assistance. Owing to the role of management accounting and cost calculations, the definition of healthcare professionals as clients or users, and clinical results relevance, it is necessary to adapt the balanced scorecard to the specific characteristics of the clinical field, redefining both perspectives and indicators. PMID- 26262747 TI - [ACCEPTANCE OF PULP FRUIT BEVERAGES FORTIFIED WITH FERROUS FUMARATE; AN ALTERNATIVE SUPPLEMENT FOR A HEALTH PROGRAM]. AB - INTRODUCTION: undernutrition and individual nutrients deficiencies are common public health problems worldwide and Mexico is not the exception, where the highest prevalence occurs in rural areas. One way to solve these nutritional deficiencies is with the use of dietary supplements. However, these supplements need to be readily available for and accepted by the objective population. OBJECTIVES: to develop a flavored-multivitamin supplement (MVS) for the Health and Nutrition Program for Indigenous People (PSNPI-Mexico) and to evaluate its acceptance by 6 to 24 months old infants in rural and urban areas. METHODS: the MVS was developed in three different flavors, their vitamin and mineral content in accordance with PSNPIs guidelines. Acceptance of the MVS by the infants was evaluated with "scale faces" and this was further corroborated in the 6 to 12 mo by registering the amount consumed. The differences in acceptance by age and gender, as well as locations (urban vs rural) were determined with chi-squared test. RESULTS: the MVS developed for this study constitute a better alternative to supplement currently used by PSNPI. PMID- 26262748 TI - [GENETIC AND METABOLIC URGENCIES IN THE NEONATAL INTENSIVE CARE UNIT: MAPLE SYRUP URINE DISEASE]. AB - Maple syrup urine disease (MSUD) is a hereditary disorder of branched chain amino/keto acid metabolism, caused by a decreased activity of the branched-chain alpha- ketoacid dehydrogenase complex (BCKAD), which leads to abnormal elevated plasma concentrations of branched-chain amino acids (BCAAs) clinically manifested as a heavy burden for Central Nervous system. The toxic accumulation of substrates promotes the development of a severe and rapidly progressive neonatal encephalopathy if treatment is not immediately given. This disorder has a specific medical management in acute phase in order to minimize mortality and morbidity. For all those reasons, it is important to include the MSUD as a possible diagnosis in a encephalopathic newborn. We present a colombian newborn with classical MSUD with fatal outcome as an example of metabolic emergency and a differential diagnosis in the encephalopathic newborn. PMID- 26262749 TI - [INVASIVE TECHNIQUES AND INTRAOPERATIVE ECHOGRAPHY IN THE LOCALIZATION OF INSULINOMAS; A CASE REPORT]. AB - The insulinoma is the most common pancreatic neuroendocrine tumor. Surgery is curative in most cases, an appropriate preoperative localization allows a minimal invasive surgical technique for keeping the exo and endocrine function of the pancreas. Some authors suggest the use of invasive localization techniques just in cases with non-identified tumor lesion, others recommend their routinely use. We describe a case with clinical and biochemical diagnosis of insulinoma, conventional image studies revealed a tumor image in the pancreas which corresponded to a lipoma, the intraoperative ultrasound allowed the localization of the real tumor, but body-tail pancreatectomy was performed due to pancreatic necrosis in relation with the duration of the surgery. The systematic use of invasive localization techniques as the intra-arterial calcium stimulation and the pancreatic intraoperative ultrasound would allow a better localization of insulinoma for avoiding complications and associated morbidity. PMID- 26262750 TI - [LONG-TERM FULMINANT HEPATIC FAILURE IN PATIENTS UNDERGOING GASTRIC BYPASS FOR MORBID OBESITY]. AB - Morbid obesity is a risk factor for numerous diseases including liver disease with an incidence of hepatic steatosis from 70 to 80%. Although surgical treatment is effective in reducing weight, its effects on the liver have not been established convincingly. We report 2 cases of patients with bariatric surgery and who had a fulminant hepatic failure resulting in death. METHODS: case N.o 1: a 36-year-obesity intervened in 1995 with VBG with BMI 52.5 to reganancia weight back after revision surgery is performed in 2009 performed distal gastric bypass. Case N.o 2: 42 Woman surgery for obesity in 2009 by distal gastric bypass with a BMI of 51 and placement of prophylactic Composix kugel midline mesh. After 3 years with good weight loss, presents abscess wall and enterocutaneous fistula he was surgically intervene. extracting mesh, identifying themselves two fistulas in alimentary and common intestinals loops that are removed and new anastomosis was performed. RESULTS: case N.o 1: at 2 months of revision surgery, tje patient starts vomiting secondary to stenosis of gastrojejunostomy anastomosis and symptoms of progressive jaundice, ascites and encephalopathy fulminant hepatic failure resulting in death. Case N.o 2: in the immediate postoperative period starts increased drainage of debit and rise of liver enzymes cytolysis and coagulopathy. It reinterviene on suspicion of anastomotic leak and abdominal Sepsis, developing fulminant hepatic failure with coagulopathy and encephalopathy is treated by MARS system, and died within 4 hours of the onset of therapy. CONCLUSIONS: although current surgical techniques of bariatric surgery are considered quite safe, there have been cases of hepatic failure, unclear whether this would relate to the progression of a preexisting steatohepatitis, or may have other predisposing factors related to surgery. Treatments available, the emergency orthotopic liver transplantation is one of the best interventions. For our patients the outcome was fatal triggering the death of both. In both cases presented a septic shock with positive ascitic fluid cultures to multiresistant microorganisms, and both had revision surgery. Unfortunately the factors that can influence that occur after bariatric surgery such complications, and probably will be grounds for future studies are unknown. PMID- 26262751 TI - Magnetic Relaxation in Single-Electron Single-Ion Cerium(III) Magnets: Insights from Ab Initio Calculations. AB - Detailed ab initio calculations were performed on two structurally different cerium(III) single-molecule magnets (SMMs) to probe the origin of magnetic anisotropy and to understand the mechanism of magnetic relaxations. The complexes [Ce(III){Zn(II)(L)}2(MeOH)]BPh4 (1) and [Li(dme)3][Ce(III)(cot'')2] (1; L=N,N,O,O tetradentate Schiff base ligand; 2; DME=dimethoxyethane, COT''=1,4 bis(trimethylsilyl)cyclooctatetraenyldianion), which are reported to be zero field and field-induced SMMs with effective barrier heights of 21.2 and 30 K respectively, were chosen as examples. CASSCF+RASSI/SINGLE_ANISO calculations unequivocally suggest that mJ|+/-5/2> and |+/-1/2> are the ground states for complexes 1 and 2, respectively. The origin of these differences is rooted back to the nature of the ligand field and the symmetry around the cerium(III) ions. Ab initio magnetisation blockade barriers constructed for complexes 1 and 2 expose a contrasting energy-level pattern with significant quantum tunnelling of magnetisation between the ground state Kramers doublet in complex 2. Calculations performed on several model complexes stress the need for a suitable ligand environment and high symmetry around the cerium(III) ions to obtain a large effective barrier. PMID- 26262752 TI - N Doping to ZnO Nanorods for Photoelectrochemical Water Splitting under Visible Light: Engineered Impurity Distribution and Terraced Band Structure. AB - Solution-based ZnO nanorod arrays (NRAs) were modified with controlled N doping by an advanced ion implantation method, and were subsequently utilized as photoanodes for photoelectrochemical (PEC) water splitting under visible light irradiation. A gradient distribution of N dopants along the vertical direction of ZnO nanorods was realized. N doped ZnO NRAs displayed a markedly enhanced visible light-driven PEC photocurrent density of ~160 MUA/cm(2) at 1.1 V vs. saturated calomel electrode (SCE), which was about 2 orders of magnitude higher than pristine ZnO NRAs. The gradiently distributed N dopants not only extended the optical absorption edges to visible light region, but also introduced terraced band structure. As a consequence, N gradient-doped ZnO NRAs can not only utilize the visible light irradiation but also efficiently drive photo-induced electron and hole transfer via the terraced band structure. The superior potential of ion implantation technique for creating gradient dopants distribution in host semiconductors will provide novel insights into doped photoelectrode materials for solar water splitting. PMID- 26262753 TI - Rotation Dynamics Do Not Determine the Unexpected Isotropy of Methyl Radical EPR Spectra. AB - A simple first-principles electronic structure computation, further qc (quantum chemistry) computation, of the methyl radical gives three equal hf (hyperfine) couplings for the three protons with the unpaired electron. The corresponding dipolar tensors were notably rhombic and had different orientations and regular magnitude components, as they should, but what the overall A-tensor was seen by the electron spin is a different story! The final g = (2.002993, 2.002993, 2.002231) tensor and the hf coupling results obtained in vacuum, at the B3LYP/EPRIII level of theory clearly indicate that in particular the above A = ( 65.19, -65.19, 62.54) MHz tensor was axial to a first approximation without considering any rotational dynamics for the CH3. This approximation was not applicable, however, for the trifluoromethyl CF3 radical, a heavier and nonplanar rotor with very anisotropic hf coupling, used here for comparison. Finally, a derivation is presented explaining why there is actually no need for the CH3 radicals to consider additional rotational dynamics in order for the electron to obtain an axially symmetric hf (hyperfine) tensor by considering the simultaneous dipolar couplings of the three protons. An additional consequence is an almost isotropic A-tensor for the electron spin of the CH3 radical. To the best of our knowledge, this point has not been discussed in the literature before. The unexpected isotropy of the EPR parameters of CH3 was solely attributed to the rotational dynamics and was not clearly separated from the overall symmetry of the species. The present theoretical results allowed a first explanation of the "forbidden" satellite lines in the CH3 EPR spectrum. The satellites are a fingerprint of the radical rotation, helping thus in distinguishing the CH3 reorientation from quantum rotation at very low temperatures. PMID- 26262754 TI - Concise Construction of the Tricyclic Core of Bullataketals Enabled by a Biomimetic Intermolecular (3 + 3) Type Cycloaddition. AB - A remarkable TFA-mediated method for the construction of a biologically interesting tricyclic ketal skeleton was uncovered by starting from a variety of readily available acylphloroglucinol and diacylphloroglucinol substrates. This approach, which mimics a biosynthetic olefin isomerization/hemiacetalization/dehydration/(3 + 3) type cycloaddition sequence through a 2H-furan-1-ium intermediate, establishes a viable synthetic strategy for efficient synthesis of bullataketals' analogs. PMID- 26262755 TI - Potential Effects of Climate Change on the Distribution of Cold-Tolerant Evergreen Broadleaved Woody Plants in the Korean Peninsula. AB - Climate change has caused shifts in species' ranges and extinctions of high latitude and altitude species. Most cold-tolerant evergreen broadleaved woody plants (shortened to cold-evergreens below) are rare species occurring in a few sites in the alpine and subalpine zones in the Korean Peninsula. The aim of this research is to 1) identify climate factors controlling the range of cold evergreens in the Korean Peninsula; and 2) predict the climate change effects on the range of cold-evergreens. We used multimodel inference based on combinations of climate variables to develop distribution models of cold-evergreens at a physiognomic-level. Presence/absence data of 12 species at 204 sites and 6 climatic factors, selected from among 23 candidate variables, were used for modeling. Model uncertainty was estimated by mapping a total variance calculated by adding the weighted average of within-model variation to the between-model variation. The range of cold-evergreens and model performance were validated by true skill statistics, the receiver operating characteristic curve and the kappa statistic. Climate change effects on the cold-evergreens were predicted according to the RCP 4.5 and RCP 8.5 scenarios. Multimodel inference approach excellently projected the spatial distribution of cold-evergreens (AUC = 0.95, kappa = 0.62 and TSS = 0.77). Temperature was a dominant factor in model-average estimates, while precipitation was minor. The climatic suitability increased from the southwest, lowland areas, to the northeast, high mountains. The range of cold evergreens declined under climate change. Mountain-tops in the south and most of the area in the north remained suitable in 2050 and 2070 under the RCP 4.5 projection and 2050 under the RCP 8.5 projection. Only high-elevations in the northeastern Peninsula remained suitable under the RCP 8.5 projection. A northward and upper-elevational range shift indicates change in species composition at the alpine and subalpine ecosystems in the Korean Peninsula. PMID- 26262756 TI - Bibliometric Assessment of European and Sub-Saharan African Research Output on Poverty-Related and Neglected Infectious Diseases from 2003 to 2011. AB - BACKGROUND: The European & Developing Countries Clinical Trials Partnership (EDCTP) is a partnership of European and sub-Saharan African countries that aims to accelerate the development of medical interventions against poverty-related diseases (PRDs). A bibliometric analysis was conducted to 1) measure research output from European and African researchers on PRDs, 2) describe collaboration patterns, and 3) assess the citation impact of clinical research funded by EDCTP. METHODOLOGY/PRINCIPAL FINDINGS: Disease-specific research publications were identified in Thomson Reuters Web of Science using search terms in titles, abstracts and keywords. Publication data, including citation counts, were extracted for 2003-2011. Analyses including output, share of global papers, normalised citation impact (NCI), and geographical distribution are presented. Data are presented as five-year moving averages. European EDCTP member countries accounted for ~33% of global research output in PRDs and sub-Saharan African countries for ~10% (2007-2011). Both regions contributed more to the global research output in malaria (43.4% and 22.2%, respectively). The overall number of PRD papers from sub-Saharan Africa increased markedly (>47%) since 2003, particularly for HIV/AIDS (102%) and tuberculosis (TB) (81%), and principally involving Southern and East Africa. For 2007-2011, European and sub-Saharan African research collaboration on PRDs was highly cited compared with the world average (NCI in brackets): HIV/AIDS 1.62 (NCI: 1.16), TB 2.11 (NCI: 1.06), malaria 1.81 (NCI: 1.22), and neglected infectious diseases 1.34 (NCI: 0.97). The NCI of EDCTP-funded papers for 2003-2011 was exceptionally high for HIV/AIDS (3.24), TB (4.08) and HIV/TB co-infection (5.10) compared with global research benchmarks (1.14, 1.05 and 1.35, respectively). CONCLUSIONS: The volume and citation impact of papers from sub-Saharan Africa has increased since 2003, as has collaborative research between Europe and sub-Saharan Africa. >90% of publications from EDCTP-funded research were published in high-impact journals and are highly cited. These findings corroborate the benefit of collaborative research on PRDs. PMID- 26262757 TI - Bone Tissue Engineering with Multilayered Scaffolds-Part I: An Approach for Vascularizing Engineered Constructs In Vivo. AB - Obtaining functional capillaries through the bulk has been identified as a major challenge in tissue engineering, particularly for critical-sized defects. In the present study, a multilayered scaffold system was developed for bone tissue regeneration, designed for through-the-thickness vascularization of the construct. The basic principle of this approach was to alternately layer mesenchymal stem cell-seeded nanofibers (osteogenic layer) with microfibers or porous ceramics (osteoconductive layer), with an intercalating angiogenic zone between the two and with each individual layer in the microscale dimension (100 400 MUm). Such a design can create a scaffold system potentially capable of spatially distributed vascularization in the overall bulk tissue. In the cellular approach, the angiogenic zone consisted of collagen/fibronectin gel with endothelial cells and pericytes, while in the acellular approach, cells were omitted from the zone without altering the gel composition. The cells incorporated into the construct were analyzed for viability, distribution, and organization of cells on the layers and vessel development in vitro. Furthermore, the layered constructs were implanted in the subcutaneous space of nude mice and the processes of vascularization and bone tissue regeneration were followed by histological and energy-dispersive X-ray spectroscopy (EDS) analysis. The results indicated that the microenvironment in the angiogenic zone, microscale size of the layers, and the continuously channeled architecture at the interface were adequate for infiltrating host vessels through the bulk and vascularizing the construct. Through-the-thickness vascularization and mineralization were accomplished in the construct, suggesting that a suitably bioengineered layered construct may be a useful design for regeneration of large bone defects. PMID- 26262759 TI - Highly Sensitive Near-Infrared Fluorophores for in Vivo Detection of Amyloid-beta Plaques in Alzheimer's Disease. AB - Alzheimer's disease (AD) is pathologically characterized by the accumulation of beta-amyloid (Abeta) deposits in the parenchymal and cortical brain. In this work, we designed, synthesized, and evaluated a series of near-infrared (NIR) probes with electron donor-acceptor end groups interacting through a pi conjugated system for the detection of Abeta deposits in the brain. Among these probes, 3b and 3c had excellent fluorescent properties (emission maxima > 650 nm and high quantum yields) and displayed high sensitivity and high affinities to Abeta aggregates (3b, Kd = 8.8 nM; 3c, Kd = 1.9 nM). Both 3b and 3c could readily penetrate the blood-brain barrier with high initial brain uptake and fast to moderate washout from the brain. In vivo NIR imaging revealed that 3b and 3c could efficiently differentiate transgenic and wild-type mice. In summary, our research provides new hints for developing smarter and more activatable NIR probes targeting Abeta. PMID- 26262760 TI - Does the Percutaneous Internal Ring Suturing Technique Impair Testicular Vascularization in Children Undergoing Inguinal Hernia Repair? AB - PURPOSE: The aim of this study was to evaluate the effect of the percutaneous internal ring suturing (PIRS) technique on testicular vascularization when used for inguinal hernia repair in children. SUBJECTS AND METHODS: In this prospective study, 49 boys older than 1 year who had been diagnosed with unilateral inguinal hernia were evaluated. Hernias were repaired using the laparoscopic PIRS technique. The testes of each patient were examined using Doppler ultrasound at the preoperative, early postoperative, and late postoperative periods. Peak systolic velocity (PSV), end diastolic velocity (EDV), and resistivity index (RI) of the intratesticular centripetal and testicular capsular arteries were determined. RESULTS: PSV, EDV, and RI of the centripetal and capsular arteries were similar between preoperative, early postoperative, and late postoperative periods, with no statistically significant differences detected. CONCLUSIONS: Testicular vascularization was not affected by hernia repair using the PIRS technique in our study. We therefore conclude that PIRS is a safe technique for inguinal hernia repair with respect to testicular vascularization. PMID- 26262761 TI - The Role of Laparoscopy in Penetrating Abdominal Trauma: Our Initial Experience. AB - BACKGROUND: Diagnostic and therapeutic laparoscopy is a known approach in managing patients with penetrating abdominal trauma (PAT). However, multiple controversies exist on indications, contraindications, and its appropriateness. The aim of this study was to evaluate the appropriateness of diagnostic and therapeutic laparoscopy in patients with PAT at Dr George Mukhari Academic Hospital, Pretoria, South Africa. MATERIALS AND METHODS: This was a retrospective, observational study. All patients with PAT managed by diagnostic and therapeutic laparoscopy during 2012-2013 were included. Recorded indications and contraindications, the mechanism of injury, the anatomical location of injury, intraoperative findings, reasons for conversion, and adverse outcomes (complications, reoperations and mortality) were analyzed in every case. RESULTS: One hundred fourteen patients were included. Stab injuries were sustained by 81 (71%) patients, and 33 (29%) patients sustained gunshot wounds (GSW) to the abdomen. The conversion rate was 7%. The operation was completed laparoscopically in 106 patients: 79 with stab wounds (74.5%) and 27 with GSW (25.5%). Laparoscopy was diagnostic for 44 patients (41.5%) and therapeutic for 62 patients (58.5%). In total, 13 patients (12%) required re-intervention, and 2 patients died (1.9%). The complications were not specific to the laparoscopic approach. No missed injuries were reported in the study. CONCLUSIONS: Diagnostic and therapeutic laparoscopy in patients with PAT is an appropriate management in hemodynamically stable patients or those responsive to initial resuscitation. The location of injuries is not a limiting factor, although it affects placement of ports. The conversion is not a complication but rather the correct way of completing the operation in an appropriate situation. It should be considered in patients with extensive intraabdominal bleeding suggesting the possibility of major vessel injury, a significant deterioration of the patient, and the complexity of injuries requiring a prolonged laparoscopic procedure. PMID- 26262762 TI - An Easy and Safe Technique for Laparoscopic Pyloromyotomy: Using a Vascular Clamp for Stabilization of the Pylorus. AB - BACKGROUND: Laparoscopic pyloromyotomy (LP) is a well-established approach for treating hypertrophic pyloric stenosis. Although grasping the pylorus with forceps is important in LP, it requires a high level of surgical skill. To make this approach easier, in 2008 we introduced the method of Dozier and Kim, in which a vascular clamp (VC) is used for grasping the pylorus (LP with VC). Here, we retrospectively compared results between traditional LP (TLP) and LP with VC. MATERIALS AND METHODS: Forty-three patients underwent LP with VC, whereas 194 patients underwent TLP. Two ports in the umbilicus and the left flank are common in both procedures. Instead of a right flank port, however, in LP with VC, we directly insert a VC to grasp the pylorus. RESULTS: Patients' characteristics were not different between the two groups. There was only one wound infection and no major complication associated with LP with VC, whereas there were three major complications in TLP. Our hospital is a pediatric teaching institution in Japan where many surgeons perform their first LP. Twenty-eight surgeons performed their first LP in our hospital in the past 17 years, and LP with VC was the first LP for nine. The operative time for surgeons' first LP was significantly shorter with LP with VC than with TLP, based on Welch's t test (42.8 versus 54.4 minutes; P = .048). CONCLUSIONS: Our results suggest that LP with VC is an easy and safe technique, and it is recommended for beginners in laparoscopic surgery. PMID- 26262763 TI - The Guidance Impact of Preoperative Magnetic Resonance Cholangiopancreatography on Laparoscopic Cholecystectomy. AB - BACKGROUND: Detailed preoperative delineation of biliary tract anatomy plays a pivotal role in guiding surgeons completing laparoscopic cholecystectomy (LC) smoothly. Hereby, we retrospectively investigated the potential impact of preoperative magnetic resonance cholangiopancreatography (MRCP) on LC. PATIENTS AND METHODS: In this study, clinical data of LC patients who received conventional preoperative examinations from January 2008 to December 2010 (Ctrl group, n = 300) versus conventional examinations plus extra preoperative MRCP assessment between January 2011 and December 2013 (MRCP group, n = 300) were randomly retrieved. The ratios of conversion to open cholecystectomy and various postoperative morbidities were respectively analyzed. RESULTS: In total, the incidences of operation conversion, postoperative remnant cystic duct stone, and choledocholithiasis in the MRCP group were 12 (4.0%), 1 (0.3%), and 2 (0.7%), respectively, all evidently lower than those in the Ctrl group: 41 (13.7%), 7 (2.3%), and 9 (3.0%). In addition, the MRCP group also presented with fewer cases of bile duct injury and incidental gallbladder carcinoma compared with the Ctrl group (1 versus 5 and 1 versus 2, respectively), although none of the variances was statistically significant. CONCLUSIONS: Our results demonstrated that preoperative MRCP had a robust safeguarding effect on LC and deserves further promotion. PMID- 26262764 TI - Effect of Tracheal Cuff Shape on Intracuff Pressure Change During Robot-Assisted Laparoscopic Surgery: The Tapered-Shaped Cuff Tube Versus the Cylindrical-Shaped Cuff Tube. AB - BACKGROUND: Although the cuff of tracheal tubes can reduce airflow leakage and prevent aspiration, excessive intracuff pressure can cause tracheal mucosal injury. Robot-assisted laparoscopic surgery (RALS) can increase intracuff pressure by the Trendelenburg position and pneumoperitoneum. The aim of our current study was to investigate the effect of tracheal cuff shape on the intracuff pressure increase by comparing two different-shaped cuffs during RALS. MATERIALS AND METHODS: Ninety-eight patients undergoing RALS were allocated randomly into two groups (tapered-shaped cuff [TSC] and cylindrical-shaped cuff [CSC] groups). The intracuff pressure was measured at nine specific time points: after intubation, immediately after surgical preparation (Trendelenburg position with CO2 insufflation), at 5, 10, 15, 30, 60, and 90 minutes after surgical preparation, and at the end of surgery. Postintubation airway symptoms were measured by assessing sore throat, hoarseness, and excessive cough 1 hour after postanesthesia care unit admission. RESULTS: Intracuff pressure significantly increased during surgery in both groups. The trend of intracuff pressure change decreased in the TSC group compared with the CSC group, although no statistically significant changes were found (P=.450). Also, there were no statistically significant differences in the postintubation airway symptom between the two groups. CONCLUSIONS: The TSC tube has a tendency to decrease intracuff pressure change compared with the CSC tube during RALS. However, neither of them was beneficial in preventing intraoperative intracuff pressure increase during RALS. PMID- 26262765 TI - Can the Long-Term Complications of Adjustable Gastric Banding Be Overcome? Preliminary Results of Adding Gastric Plication in Patients with Impending Gastric Band Failure. AB - BACKGROUND: A small percentage of patients fitted with a gastric band still experience "failure." Here, the authors demonstrate the safety and feasibility of band preserving-laparoscopic gastric plication (BP-LGP), which was designed to improve weight loss and decrease gastric band adjustment frequency and thereby improve patient quality of life. MATERIALS AND METHODS: All 6 patients involved in this study had a gastric band in place for more than 1 year; the median interval from gastric banding to BP-LGP was 31.7 months (range, 19.7-49.9 months). Five (83.3%) patients were female. Preoperative median body mass index (BMI) at gastric banding was 35.4 kg/m(2) (range, 31.9-43.9 kg/m(2)), median nadir BMI with the gastric band was 25.7 kg/m(2) (range, 20.9-31.0 kg/m(2)), and percentage excess BMI loss (%EBMIL) ranged from 24.3% to 123.6%. Indications for BP-LGP were as follows: chronic gastric prolapse in 2 patients (33.3%), pouch esophageal dilatation in 3 (50.0%), and insufficient weight loss in 4 (66.6%), which included 2 patients with weight loss failure (%EBMIL of <30%). RESULTS: The 6 patients consecutively underwent surgery from May 2014 to January 2015. No conversion to open surgery was necessary, and no perioperative complication or mortality occurred. Mean operative time was 190 minutes. All patients showed weight loss after revision and showed resolution of troublesome signs and symptoms. Median follow-up after revision was 7.3 months (range, 5.7-10.1 months), median BMI at last follow-up was 27.6 kg/m(2) (range, 22.7-34.0 kg/m(2)), and median %EBMIL was 75.7% (range, 21.0%-103.6%). Median fill volume before revision was 6.1 mL (range, 2.7-11.0 mL), and median fill volume after revision was 0.3 mL (range, 0.0-5.3 mL). Three patients (50%) had an empty band at last follow-up. CONCLUSIONS: This novel method of bariatric revision (modified BP-LGP) might have a role as a salvage procedure in patients with impending gastric band failure. PMID- 26262766 TI - Response validity of Persian version of P-QOL questionnaire in patients with prolapse. AB - BACKGROUND AND OBJECTIVE: Pelvic organ prolapse (POP) refers to drop of any pelvic organs into or outside of the vaginal canal or anus. This is a disabling condition that results in limitations in all aspects of women's lives, especially quality of life. The evaluation of quality of life in women with POP requires the use of a valid and reliable measure. An important aspect of validity is responsiveness. The aim of current study is to evaluate the responsiveness of P QOL questionnaire in patients with prolapse. METHODS: Women with confirmed diagnosed POP by gynecologist who were scheduled to undergo POP's treatment enrolled in the study. Quality of life as an outcome measure was evaluated before and six month after treatment besides assessing of physical index of treatment's effect (pelvic organ prolapse quantification; POP-Q). Responsiveness was evaluated using calculation of standardized response mean (SRM) and effect size (ES). RESULTS: Fifty women were evaluated in current study. Mean age was 43.5+/ 11.8 years old. The range of Cronbach's alpha was between 0.60 and 0.89 for all domains of P-QOL. The range of SRM for all domains was between 0.60 and 0.88. The range of ES was between 0.54 and 0.96. Score of all domains of P-QOL was statistically different between pre and post-treatment (P<0.0001). CONCLUSION: The findings of current study showed the P-QOL questionnaire has a good responsiveness in Persian language and could use to assess the impact of interventions on quality of life in patients with prolapse. PMID- 26262767 TI - Non-invasive prenatal detection of haemoglobin Bart's disease by cardiothoracic ratio during the first trimester. AB - OBJECTIVE: To evaluate the efficacy of the sonographic cardiothoracic ratio (CTR) in early pregnancy for the prediction of fetal haemoglobin (Hb) Bart's disease. STUDY DESIGN: Over a 1.5-year period at a Chinese tertiary obstetric centre, women at risk of Hb Bart's disease were given the option of a non-invasive approach to exclude an affected pregnancy between 11 weeks and 13 weeks and 6 days of gestation, with a routine rescan after a 2-week interval. The fetal CTR, a sonographic marker, was assessed, and invasive testing followed in cases of fetal cardiomegaly. The diagnosis of fetal Hb Bart's disease was based on DNA analysis from chorionic villus sampling. RESULTS: Of 154 at-risk cases studied, five cases (four at 11 weeks of gestation) were subjected to direct invasive testing because of an unsatisfactory scan. Of the remaining 149 cases, non invasive ultrasound examinations were performed successfully. Thirty-four (22.8%) affected pregnancies were revealed, including one picked up on rescan. The sensitivity and specificity of the non-invasive approach were 97.1% and 100%, respectively. The need for an invasive test was reduced by 74.7%, and all affected pregnancies except one were diagnosed before 14 weeks of gestation. CONCLUSION: CTR can differentiate reliably between pregnancies with and without Hb Bart's disease. This non-invasive approach for the exclusion of Hb Bart's disease can be used in early pregnancy. PMID- 26262768 TI - Combined ultrasound-curcumin treatment of human cervical cancer cells. AB - OBJECTIVES: Human papillomavirus (HPV) is associated with cervical cancer. Studies showed curcumin inhibits HPV oncogenes expression but curcumin has low bioavailability. The objectives were: (1) to study ultrasound enhancement of curcumin effects on HeLa, SiHa and C33A, (2) to compare two frequencies for sonoporation and (3) to detect cell-free DNA released by the treatment. STUDY DESIGN: HeLa, SiHa and C33A cells (non-HPV control) were processed and exposed to either: (1) 10MUM curcumin only, (2) 10MUM curcumin with 8s of 7.5MHz ultrasound, (3) 10MUM curcumin with 8s of 5.0MHz ultrasound, (4) control medium, or (5) 8s of 7.5MHz ultrasound. The five treated groups were incubated (48h) and analyzed by dual fluorescence apoptosis/necrosis assay. DNA in spent media was analyzed by capillary analysis. RESULTS: Combined curcumin ultrasound resulted in 9-, 12- and 16-fold higher necrosis in HeLa, SiHa and C33A cells respectively. Increased necrosis correlated with higher ultrasound frequencies. There was increased apoptosis in HeLa or SiHa cells with the combined treatment. Curcumin alone resulted in a lesser 2-4-fold increase in necrosis in the groups. Cell-free DNA was detected in the spent media of HeLa and SiHa but not C33A cultures. CONCLUSIONS: The results showed enhanced necrosis in cervical carcinoma cell lines after combined treatment and confirmed the ultrasound capacity to increase effectiveness of curcumin. Cancer cells were smaller post-treatment suggesting microtubule structural disruption. Cell-free DNA was low molecular weight consistent with lysed host cell. PMID- 26262770 TI - Three-Phase Coexistence in Colloidal Rod-Plate Mixtures. AB - Aqueous suspensions of clay particles, such as montmorillonite (MMT) platelets and sepiolite (Sep) rods, tend to form gels at concentrations around 1 vol %. For Sep rods, adsorbing sodium polyacrylate to the surface allows for an isotropic nematic phase separation to be seen instead. Here, MMT is added to such Sep suspensions, resulting in a complex phase behavior. Across a range of clay concentrations, separation into three phases is observed: a lower, nematic phase dominated by Sep rods, a MMT-rich middle layer, which is weakly birefringent and probably a gel, and a dilute top phase. Analysis of phase volumes suggests that the middle layer may contain as much as 6 vol % MMT. PMID- 26262771 TI - Dose Proportionality and Pharmacokinetics of Eplerenone in Healthy Chinese Subjects. AB - BACKGROUND: Eplerenone (CAS 107724-20-9) is the first highly selective aldosterone receptor blocker and is used worldwide for treatment of hypertension and heart failure. OBJECTIVE: The objective of this study was to investigate the eplerenone pharmacokinetics in healthy Chinese subjects and assess the dose proportionality over the therapeutic dose range. METHODS: A single-dose, randomized, 6-sequence, 3-treatment, 3-period crossover, open label study was conducted in 12 healthy Chinese subjects, who received 3 doses of eplerenone in random order (25, 50, 100 mg). The power model was used to evaluate the dose proportionality of eplerenone. The pharmacokinetic study of multiple-dose of eplerenone was also conducted. RESULTS: After single-dose oral administration, the mean C max value increased from 489 to 1 641 ng/mL, and the mean AUC 0-t value increased from 3 030 to 10 893 ng/mL.h with an increase in dose from 25 to 100 mg, respectively. The mean value for terminal T 1/2 was approximate 3 h with no significant differences among different dose groups. Though dose proportionality of eplerenone was inconclusive in Chinese subjects over the dose range of 25-100 mg, the maximal proportionality dose range (rho1) was 2.06 based on power model. Steady state could achieve within at least 4 days and no accumulation was observed after multiple-dose of eplerenone. CONCLUSION: Dose proportionality was inconclusive in over the dose range of 25-100 mg; however, linear pharmacokinetics could be considered when dose ratio is no more than 2.06. PMID- 26262773 TI - The effect of the degree of left renal vein constriction on the development of adolescent varicocele in Sprague-Dawley rats. AB - Experimental models have allowed inquiry into the pathophysiology of varicocele (VC) beyond that possible with human patients. A randomized controlled study in rats was designed to clarify the influence of the degree of left renal vein constriction on the development of adolescent VC. Fifty adolescent male Sprague Dawley rats (Rattus norvegicus) were randomly assigned to five groups of 10: the experimental groups (I-IV) underwent partial ligation of left renal veins with 0.5-, 0.6-, 0.7-, and 0.8-mm diameter needles, respectively. The control group (V) underwent a sham operation. The diameter of the left spermatic vein (LSV) was measured at baseline and 30 days postoperatively. In addition, the lesion of the left kidney was examined with the naked eye and assessed by Masson's trichrome staining. VC was successfully induced in 2 (20%), 4 (40%), 7 (70%), and 10 (100%) rats in groups I-IV, respectively. The other rats failed to develop VCs primarily due to left renal atrophy. No VC was observed in group V. The postsurgical LSV diameters in VC rats in groups III and IV were 1.54 +/- 0.16 and 1.49 +/- 0.13 mm, respectively (P > 0.05), and their increments were 1.36 +/- 0.10 and 1.31 +/- 0.10 mm, respectively (P > 0.05). These results suggest that suitable constriction of the left renal vein is critical for adolescent VC development. In addition, the 0.8-mm diameter needle may be more suitable for inducing left renal vein constriction in adolescent rat models. PMID- 26262774 TI - Novel phenotype of mouse spermatozoa following deletion of nine beta-defensin genes. AB - beta-defensin peptides are a large family of antimicrobial peptides. Although they kill microbes in vitro and interact with immune cells, the precise role of these genes in vivo remains uncertain. Despite their inducible presence at mucosal surfaces, their main site of expression is the epididymis. Recent evidence suggests that a major function of these peptides is in sperm maturation. In addition to previous work suggesting this, work at the MRC Human Genetics Unit, Edinburgh, has shown that homozygous deletion of a cluster of nine beta defensin genes in the mouse results in profound male sterility. The spermatozoa derived from the mutants had reduced motility and increased fragility. Epididymal spermatozoa isolated from the cauda region of the homozygous mutants demonstrated precocious capacitation and increased spontaneous acrosome reactions compared with those from wild-types. Despite this, these mutant spermatozoa had reduced ability to bind to the zona pellucida of oocytes. Ultrastructural examination revealed a disintegration of the microtubule structure of mutant-derived spermatozoa isolated from the epididymal cauda region, but not from the caput. Consistent with premature acrosome reaction and hyperactivation, spermatozoa from mutant animals had significantly increased intracellular calcium content. This work demonstrates that in vivo beta-defensins are essential for successful sperm maturation, and that their disruption alters intracellular calcium levels, which most likely leads to premature activation and spontaneous acrosome reactions that result in hyperactivation and loss of microtubule structure of the axoneme. Determining which of the nine genes are responsible for the phenotype and the relevance to human sperm function is important for future work on male infertility. PMID- 26262772 TI - Games for Health for Children-Current Status and Needed Research. AB - Videogames for health (G4H) offer exciting, innovative, potentially highly effective methods for increasing knowledge, delivering persuasive messages, changing behaviors, and influencing health outcomes. Although early outcome results are promising, additional research is needed to determine the game design and behavior change procedures that best promote G4H effectiveness and to identify and minimize possible adverse effects. Guidelines for ideal use of different types of G4H by children and adolescents should be elucidated to enhance effectiveness and minimize adverse effects. G4H stakeholders include organizational implementers, policy makers, players and their families, researchers, designers, retailers, and publishers. All stakeholders should be involved in G4H development and have a voice in setting goals to capitalize on their insights to enhance effectiveness and use of the game. In the future, multiple targeted G4H should be available to meet a population's diverse health needs in developmentally appropriate ways. Substantial, consistent, and sophisticated research with appropriate levels of funding is needed to realize the benefits of G4H. PMID- 26262775 TI - Chronic exposure to ethanol in male mice may be associated with hearing loss in offspring. AB - Although paternal ethanol (EtOH) abuse has been shown to affect the growth and behavior of offspring, the exact molecular and mechanistic basis remains largely unclear. Methylation alterations in imprinted genes may be related to well documented teratogenic effects of ethanol. Here we show that chronic paternal ethanol exposure increases the susceptibility to abnormal behavior in offspring through male game epigenetic alteration. In our study, different doses of ethanol (0, 1.1, 3.3 g kg-1 ) were administered intra-gastrically to male mice and decreased sperm motility was found in the highest ethanol-exposed group compared with the controls. Data also showed a dose-dependent increase in deaf mice of the paternally ethanol-exposed groups. The methylation of H19, Peg3, Ndn and Snrpn was assessed in paternal spermatozoa and in the cerebral cortices of deaf mice. EtOH affected methylation of Peg3 (CpG 3, 7 and 9) in paternal spermatozoa and in the cerebral cortices of deaf mice, but the level of mRNA expression did not change, suggesting that other gene regulation may be involved in these processes. Overall, chronic paternal ethanol exposure could alter the methylation of imprinted genes in sire spermatozoa that could also be passed on to offspring, giving rise to developmental disorders. Our results provide possible epigenetic evidence for a paternal ethanol exposure contribution to Fetal Alcohol Syndrome (FAS). PMID- 26262776 TI - Implementation and Operational Research: Decentralization Does Not Assure Optimal Delivery of PMTCT and HIV-Exposed Infant Services in a Low Prevalence Setting. AB - BACKGROUND: The consequences of decentralizing prevention of mother-to-child HIV transmission and HIV-exposed infant services to antenatal care (ANC)/labor and delivery (L&D) sites from dedicated HIV care and treatment (C&T) centers remain unknown, particularly in low prevalence settings. METHODS: In a cohort of mother infant pairs, we compared delivery of routine services at ANC/L&D and C&T facilities in Kinshasa, Democratic Republic of Congo from 2010-2013, using methods accounting for competing risks (eg, death). Women could opt to receive interventions at 90 decentralized ANC/L&D sites, or 2 affiliated C&T centers. Additionally, we assessed decentralization's population-level impacts by comparing proportions of women and infants receiving interventions before (2009 2010) and after (2011-2013) decentralization. RESULTS: Among newly HIV-diagnosed women (N = 1482), the 14-week cumulative incidence of receiving the package of CD4 testing and zidovudine or antiretroviral therapy was less at ANC/L&D [66%; 95% confidence interval (CI): 63% to 69%] than at C&T (88%; 95% CI: 83% to 92%) sites (subdistribution hazard ratio, 0.62; 95% CI: 0.55 to 0.69). Delivery of cotrimoxazole and DNA polymerase chain reaction testing to HIV-exposed infants (N = 1182) was inferior at ANC/L&D sites (subdistribution hazard ratio, 0.84; 95% CI: 0.76 to 0.92); the 10-month cumulative incidence of the package at ANC/L&D sites was 89% (95% CI: 82% to 93%) versus 97% (95% CI: 93% to 99%) at C&T centers. Receipt of the pregnancy (20% of 1518, to 64% of 1405) and infant (16% 31%) packages improved post decentralization. CONCLUSIONS: Services were delivered less efficiently at ANC/L&D sites than C&T centers. Although access improved with decentralization, its potential cannot be realized without sufficient and sustained support. PMID- 26262777 TI - Brief Report: Dolutegravir Plus Abacavir/Lamivudine for the Treatment of HIV-1 Infection in Antiretroviral Therapy-Naive Patients: Week 96 and Week 144 Results From the SINGLE Randomized Clinical Trial. AB - The SINGLE study was a randomized, double-blind, noninferiority study that evaluated the safety and efficacy of 50 mg dolutegravir + abacavir/lamivudine versus efavirenz/tenofovir/emtricitabine in 833 ART-naive HIV-1 + participants. Of 833 randomized participants, 71% in the dolutegravir + abacavir/lamivudine arm and 63% in the efavirenz/tenofovir/emtricitabine arm maintained viral loads of <50 copies per milliliter through W144 (P = 0.01). Superior efficacy was primarily driven by fewer discontinuations due to adverse events in the dolutegravir + abacavir/lamivudine arm [dolutegravir + abacavir/lamivudine arm, 16 (4%); efavirenz/tenofovir/emtricitabine arm, 58 (14%)] through W144 [corrected]. No treatment-emergent integrase or nucleoside resistance was observed in dolutegravir + abacavir/lamivudine recipients through W144. PMID- 26262779 TI - Behavioural and brain responses related to Internet search and memory. AB - The ready availability of data via searches on the Internet has changed how many people seek and perhaps store and recall information, although the brain mechanisms underlying these processes are not well understood. This study investigated brain mechanisms underlying Internet-based vs. non-Internet-based searching. The results showed that Internet searching was associated with lower accuracy in recalling information as compared with traditional book searching. During functional magnetic resonance imaging, Internet searching was associated with less regional brain activation in the left ventral stream, the association area of the temporal-parietal-occipital cortices, and the middle frontal cortex. When comparing novel items with remembered trials, Internet-based searching was associated with higher brain activation in the right orbitofrontal cortex and lower brain activation in the right middle temporal gyrus when facing those novel trials. Brain activations in the middle temporal gyrus were inversely correlated with response times, and brain activations in the orbitofrontal cortex were positively correlated with self-reported search impulses. Taken together, the results suggest that, although Internet-based searching may have facilitated the information-acquisition process, this process may have been performed more hastily and be more prone to difficulties in recollection. In addition, people appear less confident in recalling information learned through Internet searching and that recent Internet searching may promote motivation to use the Internet. PMID- 26262778 TI - Brief Report: Consequences of Presentation With Advanced HIV Disease in Pregnancy: Data From a National Study in Italy. AB - Among 469 women with a diagnosis of HIV in pregnancy, 74 (15.8%) presented with less than 200 CD4 cells per cubic millimeter. The only variable significantly associated with this occurrence was African origin (odds ratio: 2.22, 95% confidence intervals: 1.32 to 3.75, P = 0.003). Four women with low CD4 (5.6%), compared with none with higher CD4 counts, had severe AIDS-defining conditions (P < 0.001) during pregnancy or soon after delivery, and one transmitted HIV to the newborn. Early preterm delivery (<32 weeks) was significantly more frequent with low CD4 (6.2% vs. 1.4%, P = 0.015). An earlier access to HIV testing, particularly among immigrants of African origin, can prevent severe HIV-related morbidity. PMID- 26262780 TI - Manifold Based Optimization for Single-Cell 3D Genome Reconstruction. AB - The three-dimensional (3D) structure of the genome is important for orchestration of gene expression and cell differentiation. While mapping genomes in 3D has for a long time been elusive, recent adaptations of high-throughput sequencing to chromosome conformation capture (3C) techniques, allows for genome-wide structural characterization for the first time. However, reconstruction of "consensus" 3D genomes from 3C-based data is a challenging problem, since the data are aggregated over millions of cells. Recent single-cell adaptations to the 3C-technique, however, allow for non-aggregated structural assessment of genome structure, but data suffer from sparse and noisy interaction sampling. We present a manifold based optimization (MBO) approach for the reconstruction of 3D genome structure from chromosomal contact data. We show that MBO is able to reconstruct 3D structures based on the chromosomal contacts, imposing fewer structural violations than comparable methods. Additionally, MBO is suitable for efficient high-throughput reconstruction of large systems, such as entire genomes, allowing for comparative studies of genomic structure across cell-lines and different species. PMID- 26262781 TI - A PIECE OF MY MIND. A Story I Hope Ends Up Being True. PMID- 26262784 TI - Afternoon in the Cluny Garden, Paris: Charles Courtney Curran. PMID- 26262785 TI - Learning About Competition From the UK's National Health Service. PMID- 26262792 TI - Racial Bias in Health Care and Health: Challenges and Opportunities. PMID- 26262793 TI - Improving Access to Kidney Transplantation: Referral Is Not Enough. PMID- 26262794 TI - Hypoxemic Episodes and Adverse Neurodevelopmental Outcome in Extremely Preterm Infants. PMID- 26262795 TI - Effects of Testosterone Administration for 3 Years on Subclinical Atherosclerosis Progression in Older Men With Low or Low-Normal Testosterone Levels: A Randomized Clinical Trial. AB - IMPORTANCE: Testosterone use in older men is increasing, but its long-term effects on progression of atherosclerosis are unknown. OBJECTIVE: To determine the effect of testosterone administration on subclinical atherosclerosis progression in older men with low or low-normal testosterone levels. DESIGN, SETTING, AND PARTICIPANTS: Testosterone's Effects on Atherosclerosis Progression in Aging Men (TEAAM) was a placebo-controlled, double-blind, parallel-group randomized trial involving 308 men 60 years or older with low or low-normal testosterone levels (100-400 ng/dL; free testosterone <50 pg/mL), recruited at 3 US centers. Recruitment took place between September 2004 and February 2009; the last participant completed the study in May 2012. INTERVENTIONS: One hundred fifty-six participants were randomized to receive 7.5 g of 1% testosterone and 152 were randomized to receive placebo gel packets daily for 3 years. The dose was adjusted to achieve testosterone levels between 500 and 900 ng/dL. MAIN OUTCOMES AND MEASURES: Coprimary outcomes included common carotid artery intima media thickness and coronary artery calcium; secondary outcomes included sexual function and health-related quality of life. RESULTS: Baseline characteristics were similar between groups: patients were a mean age of 67.6 years; 42% had hypertension; 15%, diabetes; 15%, cardiovascular disease; and 27%, obesity. The rate of change in intima-media thickness was 0.010 mm/year in the placebo group and 0.012 mm/year in the testosterone group (mean difference adjusted for age and trial site, 0.0002 mm/year; 95% CI, -0.003 to 0.003, P = .89). The rate of change in the coronary artery calcium score was 41.4 Agatston units/year in the placebo group and 31.4 Agatston units/year in the testosterone group (adjusted mean difference, -10.8 Agatston units/year; 95% CI, -45.7 to 24.2; P = .54). Changes in intima-media thickness or calcium scores were not associated with change in testosterone levels among individuals assigned to receive testosterone. Sexual desire, erectile function, overall sexual function scores, partner intimacy, and health-related quality of life did not differ significantly between groups. Hematocrit and prostate-specific antigen levels increased more in testosterone group. CONCLUSIONS AND RELEVANCE: Among older men with low or low-normal testosterone levels, testosterone administration for 3 years vs placebo did not result in a significant difference in the rates of change in either common carotid artery intima-media thickness or coronary artery calcium nor did it improve overall sexual function or health-related quality of life. Because this trial was only powered to evaluate atherosclerosis progression, these findings should not be interpreted as establishing cardiovascular safety of testosterone use in older men. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00287586. PMID- 26262796 TI - Variation in Dialysis Facility Referral for Kidney Transplantation Among Patients With End-Stage Renal Disease in Georgia. AB - IMPORTANCE: Dialysis facilities in the United States are required to educate patients with end-stage renal disease about all treatment options, including kidney transplantation. Patients receiving dialysis typically require a referral for kidney transplant evaluation at a transplant center from a dialysis facility to start the transplantation process, but the proportion of patients referred for transplantation is unknown. OBJECTIVE: To describe variation in dialysis facility level referral for kidney transplant evaluation and factors associated with referral among patients initiating dialysis in Georgia, the US state with the lowest kidney transplantation rates. DESIGN, SETTING, AND PARTICIPANTS: Examination of United States Renal Data System data from a cohort of 15,279 incident, adult (18-69 years) patients with end-stage renal disease from 308 Georgia dialysis facilities from January 2005 to September 2011, followed up through September 2012, linked to kidney transplant referral data collected from adult transplant centers in Georgia in the same period. MAIN OUTCOMES AND MEASURES: Referral for kidney transplant evaluation within 1 year of starting dialysis at any of the 3 Georgia transplant centers was the primary outcome; placement on the deceased donor waiting list was also examined. RESULTS: The median within-facility percentage of patients referred within 1 year of starting dialysis was 24.4% (interquartile range, 16.7%-33.3%) and varied from 0% to 75.0%. Facilities in the lowest tertile of referral (<19.2%) were more likely to treat patients living in high-poverty neighborhoods (absolute difference, 21.8% [95% CI, 14.1%-29.4%]), had a higher patient to social worker ratio (difference, 22.5 [95% CI, 9.7-35.2]), and were more likely nonprofit (difference, 17.6% [95% CI, 7.7%-27.4%]) compared with facilities in the highest tertile of referral (>31.3%). In multivariable, multilevel analyses, factors associated with lower referral for transplantation, such as older age, white race, and nonprofit facility status, were not always consistent with the factors associated with lower waitlisting. CONCLUSIONS AND RELEVANCE: In Georgia overall, a limited proportion of patients treated with dialysis were referred for kidney transplant evaluation between 2005 and 2011, but there was substantial variability in referral among facilities. Variables associated with referral were not always associated with waitlisting, suggesting that different factors may account for disparities in referral. PMID- 26262798 TI - Characteristics of Clinical Studies Conducted Over the Total Product Life Cycle of High-Risk Therapeutic Medical Devices Receiving FDA Premarket Approval in 2010 and 2011. AB - IMPORTANCE: The US Food and Drug Administration (FDA) approves high-risk medical devices, those that support or sustain human life or present potential unreasonable risk to patients, via the Premarket Approval (PMA) pathway. The generation of clinical evidence to understand device safety and effectiveness is shifting from predominantly premarket to continual study throughout the total product life cycle. OBJECTIVE: To characterize the clinical evidence generated for high-risk therapeutic devices over the total product life cycle. DESIGN AND SETTING: All clinical studies of high-risk therapeutic devices receiving initial market approval via the PMA pathway in 2010 and 2011 identified through ClinicalTrials.gov and publicly available FDA documents as of October 2014. MAIN OUTCOMES AND MEASURES: Studies were characterized by type (pivotal, studies that served as the basis of FDA approval; FDA-required postapproval studies [PAS]; or manufacturer/investigator-initiated); premarket or postmarket; status (completed, ongoing, or terminated/unknown); and design features, including enrollment, comparator, and longest duration of primary effectiveness end point follow-up. RESULTS: In 2010 and 2011, 28 high-risk therapeutic devices received initial marketing approval via the PMA pathway. We identified 286 clinical studies of these devices: 82 (28.7%) premarket and 204 (71.3%) postmarket, among which there were 52 (18.2%) nonpivotal premarket studies, 30 (10.5%) pivotal premarket studies, 33 (11.5%) FDA-required PAS, and 171 (59.8%) manufacturer/investigator initiated postmarket studies. Six of 33 (18.2%) PAS and 20 of 171 (11.7%) manufacturer/investigator-initiated postmarket studies were reported as completed. No postmarket studies were identified for 5 (17.9%) devices; 3 or fewer were identified for 13 (46.4%) devices overall. Median enrollment was 65 patients (interquartile range [IQR], 25-111), 241 patients (IQR, 147-415), 222 patients (IQR, 119-640), and 250 patients (IQR, 60-800) for nonpivotal premarket, pivotal, FDA-required PAS, and manufacturer/investigator-initiated postmarket studies, respectively. Approximately half of all studies used no comparator (pivotal: 13/30 [43.3%]; completed postmarket: 16/26 [61.5%]; ongoing postmarket: 70/153 [45.8%]). Median duration of primary effectiveness end point follow-up was 3.0 months (IQR, 3.0-12.0), 9.0 months (IQR, 0.3-12.0), and 12.0 months (IQR, 7.0 24.0) for pivotal, completed postmarket, and ongoing postmarket studies, respectively. CONCLUSIONS AND RELEVANCE: Among high-risk therapeutic devices approved via the FDA PMA pathway, total product life cycle evidence generation varied in both the number and quality of premarket and postmarket studies, with approximately 13% of initiated postmarket studies completed between 3 and 5 years after FDA approval. PMID- 26262799 TI - Young Age and Aggressive Treatment in Colon Cancer. PMID- 26262800 TI - Screening for Chronic Kidney Disease. PMID- 26262797 TI - Association Between Intermittent Hypoxemia or Bradycardia and Late Death or Disability in Extremely Preterm Infants. AB - IMPORTANCE: Extremely preterm infants may experience intermittent hypoxemia or bradycardia for many weeks after birth. The prognosis of these events is uncertain. OBJECTIVE: To determine the association between intermittent hypoxemia or bradycardia and late death or disability. DESIGN, SETTING, AND PARTICIPANTS: Post hoc analysis of data from the inception cohort assembled for the Canadian Oxygen Trial in 25 hospitals in Canada, the United States, Argentina, Finland, Germany, and Israel, including 1019 infants with gestational ages of 23 weeks 0 days through 27 weeks 6 days who were born between December 2006 and August 2010 and survived to a postmenstrual age of 36 weeks. Follow-up assessments occurred between October 2008 and August 2012. EXPOSURES: Episodes of hypoxemia (pulse oximeter oxygen saturation <80%) or bradycardia (pulse rate <80/min) for 10 seconds or longer. Values were sampled every 10 seconds within 24 hours after birth until at least 36 weeks' postmenstrual age. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of death after 36 weeks' postmenstrual age, motor impairment, cognitive or language delay, severe hearing loss, or bilateral blindness at 18 months' corrected age. Secondary outcomes were motor impairment, cognitive or language delay, and severe retinopathy of prematurity. RESULTS: Downloaded saturation and pulse rate data were available for a median of 68.3 days (interquartile range, 56.8-86.0 days). Mean percentages of recorded time with hypoxemia for the least and most affected 10% of infants were 0.4% and 13.5%, respectively. Corresponding values for bradycardia were 0.1% and 0.3%. The primary outcome was ascertained for 972 infants and present in 414 (42.6%). Hypoxemic episodes were associated with an estimated increased risk of late death or disability at 18 months of 56.5% in the highest decile of hypoxemic exposure vs 36.9% in the lowest decile (modeled relative risk, 1.53; 95% CI, 1.21-1.94). This association was significant only for prolonged hypoxemic episodes lasting at least 1 minute (relative risk, 1.66; 95% CI, 1.35-2.05 vs for shorter episodes, relative risk, 1.01; 95% CI, 0.77-1.32). Relative risks for all secondary outcomes were similarly increased after prolonged hypoxemia. Bradycardia did not alter the prognostic value of hypoxemia. CONCLUSIONS AND RELEVANCE: Among extremely preterm infants who survived to 36 weeks' postmenstrual age, prolonged hypoxemic episodes during the first 2 to 3 months after birth were associated with adverse 18-month outcomes. If confirmed in future studies, further research on the prevention of such episodes is needed. PMID- 26262801 TI - Fatigue and an Elevated White Blood Cell Count. PMID- 26262802 TI - Outcomes of Fresh and Cryopreserved Oocyte Donation. PMID- 26262803 TI - Varying Responses to Antithrombotic Treatment by Race/Ethnicity. PMID- 26262804 TI - Intervention for Acute Stroke. PMID- 26262805 TI - Varying Responses to Antithrombotic Treatment by Race/Ethnicity--Reply. PMID- 26262806 TI - Intervention for Acute Stroke--Reply. PMID- 26262807 TI - Determining the Value of Vitamin D Supplementation. PMID- 26262808 TI - Determining the Value of Vitamin D Supplementation--Reply. PMID- 26262809 TI - Incorrect Element in Figure. PMID- 26262810 TI - Incorrect Trial Description, Reference Numbering, and Case Description. PMID- 26262812 TI - Some Remarks on Alleged Degeneracy. PMID- 26262813 TI - Mucinous Colorectal Adenocarcinoma: Influence of EGFR and E-Cadherin Expression on Clinicopathologic Features and Prognosis. AB - Previous studies have shown conflicting results on epidermal growth factor receptor (EGFR) and E-cadherin expression in colorectal carcinoma and their prognostic significance. To the best of our knowledge, this study is the first to investigate EGFR and E-cadherin expression, interrelation and relation to clinicopathologic, histologic parameters, and survival in rare colorectal mucinous adenocarcinoma (MA). In this study, we studied tumor tissue specimens from 150 patients with colorectal MA and nonmucinous adenocarcinoma (NMA). High density manual tissue microarrays were constructed using modified mechanical pencil tips technique, and immunohistochemistry for EGFR and E-cadherin was performed. All relations were analyzed using established statistical methodologies. NMA expressed EGFR and E-cadherin in significantly higher rates with significant heterogenous pattern than MA. EGFR and E-cadherin positivity rates were significantly interrelated in both NMA and MA groups. In the NMA group, high EGFR expression was associated with old age, male sex, multiplicity of tumors, lack of mucinous component, and association with schistosomiasis. However, in the MA group, high EGFR expression was associated only with old age and MA subtype rather than signet ring carcinoma subtype. Conversely, high E cadherin expression in MA cases was associated with old age, fungating tumor configuration, MA subtype, and negative intratumoral lymphocytic response. However, in the NMA cases, none of these factors was statistically significant. In a univariate analysis, neither EGFR nor E-cadherin expression showed a significant impact on disease-free or overall survival. Targeted therapy against EGFR and E-cadherin may not be useful in patients with MA. Neither EGFR nor E cadherin is an independent prognostic factor in NMA or MA. PMID- 26262814 TI - Marine bacterial community structure resilience to changes in protist predation under phytoplankton bloom conditions. AB - To test whether protist grazing selectively affects the composition of aquatic bacterial communities, we combined high-throughput sequencing to determine bacterial community composition with analyses of grazing rates, protist and bacterial abundances and bacterial cell sizes and physiological states in a mesocosm experiment in which nutrients were added to stimulate a phytoplankton bloom. A large variability was observed in the abundances of bacteria (from 0.7 to 2.4 * 10(6) cells per ml), heterotrophic nanoflagellates (from 0.063 to 2.7 * 10(4) cells per ml) and ciliates (from 100 to 3000 cells per l) during the experiment (~3-, 45- and 30-fold, respectively), as well as in bulk grazing rates (from 1 to 13 * 10(6) bacteria per ml per day) and bacterial production (from 3 to 379 MUg per C l per day) (1 and 2 orders of magnitude, respectively). However, these strong changes in predation pressure did not induce comparable responses in bacterial community composition, indicating that bacterial community structure was resilient to changes in protist predation pressure. Overall, our results indicate that peaks in protist predation (at least those associated with phytoplankton blooms) do not necessarily trigger substantial changes in the composition of coastal marine bacterioplankton communities. PMID- 26262815 TI - Latitudinal variation in virus-induced mortality of phytoplankton across the North Atlantic Ocean. AB - Viral lysis of phytoplankton constrains marine primary production, food web dynamics and biogeochemical cycles in the ocean. Yet, little is known about the biogeographical distribution of viral lysis rates across the global ocean. To address this, we investigated phytoplankton group-specific viral lysis rates along a latitudinal gradient within the North Atlantic Ocean. The data show large scale distribution patterns of different virus groups across the North Atlantic that are associated with the biogeographical distributions of their potential microbial hosts. Average virus-mediated lysis rates of the picocyanobacteria Prochlorococcus and Synechococcus were lower than those of the picoeukaryotic and nanoeukaryotic phytoplankton (that is, 0.14 per day compared with 0.19 and 0.23 per day, respectively). Total phytoplankton mortality (virus plus grazer mediated) was comparable to the gross growth rate, demonstrating high turnover rates of phytoplankton populations. Virus-induced mortality was an important loss process at low and mid latitudes, whereas phytoplankton mortality was dominated by microzooplankton grazing at higher latitudes (>56 degrees N). This shift from a viral-lysis-dominated to a grazing-dominated phytoplankton community was associated with a decrease in temperature and salinity, and the decrease in viral lysis rates was also associated with increased vertical mixing at higher latitudes. Ocean-climate models predict that surface warming will lead to an expansion of the stratified and oligotrophic regions of the world's oceans. Our findings suggest that these future shifts in the regional climate of the ocean surface layer are likely to increase the contribution of viral lysis to phytoplankton mortality in the higher-latitude waters of the North Atlantic, which may potentially reduce transfer of matter and energy up the food chain and thus affect the capacity of the northern North Atlantic to act as a long-term sink for CO2. PMID- 26262816 TI - The activated sludge ecosystem contains a core community of abundant organisms. AB - Understanding the microbial ecology of a system requires that the observed population dynamics can be linked to their metabolic functions. However, functional characterization is laborious and the choice of organisms should be prioritized to those that are frequently abundant (core) or transiently abundant, which are therefore putatively make the greatest contribution to carbon turnover in the system. We analyzed the microbial communities in 13 Danish wastewater treatment plants with nutrient removal in consecutive years and a single plant periodically over 6 years, using Illumina sequencing of 16S ribosomal RNA amplicons of the V4 region. The plants contained a core community of 63 abundant genus-level operational taxonomic units (OTUs) that made up 68% of the total reads. A core community consisting of abundant OTUs was also observed within the incoming wastewater to three plants. The net growth rate for individual OTUs was quantified using mass balance, and it was found that 10% of the total reads in the activated sludge were from slow or non-growing OTUs, and that their measured abundance was primarily because of immigration with the wastewater. Transiently abundant organisms were also identified. Among them the genus Nitrotoga (class Betaproteobacteria) was the most abundant putative nitrite oxidizer in a number of activated sludge plants, which challenges previous assumptions that Nitrospira (phylum Nitrospirae) are the primary nitrite-oxidizers in activated sludge systems with nutrient removal. PMID- 26262817 TI - N2-fixation, ammonium release and N-transfer to the microbial and classical food web within a plankton community. AB - We investigated the role of N2-fixation by the colony-forming cyanobacterium, Aphanizomenon spp., for the plankton community and N-budget of the N-limited Baltic Sea during summer by using stable isotope tracers combined with novel secondary ion mass spectrometry, conventional mass spectrometry and nutrient analysis. When incubated with (15)N2, Aphanizomenon spp. showed a strong (15)N enrichment implying substantial (15)N2-fixation. Intriguingly, Aphanizomenon did not assimilate tracers of (15)NH4(+) from the surrounding water. These findings are in line with model calculations that confirmed a negligible N-source by diffusion-limited NH4(+) fluxes to Aphanizomenon colonies at low bulk concentrations (<250 nm) as compared with N2-fixation within colonies. No N2 fixation was detected in autotrophic microorganisms <5 MUm, which relied on NH4(+) uptake from the surrounding water. Aphanizomenon released about 50% of its newly fixed N2 as NH4(+). However, NH4(+) did not accumulate in the water but was transferred to heterotrophic and autotrophic microorganisms as well as to diatoms (Chaetoceros sp.) and copepods with a turnover time of ~5 h. We provide direct quantitative evidence that colony-forming Aphanizomenon releases about half of its recently fixed N2 as NH4(+), which is transferred to the prokaryotic and eukaryotic plankton forming the basis of the food web in the plankton community. Transfer of newly fixed nitrogen to diatoms and copepods furthermore implies a fast export to shallow sediments via fast-sinking fecal pellets and aggregates. Hence, N2-fixing colony-forming cyanobacteria can have profound impact on ecosystem productivity and biogeochemical processes at shorter time scales (hours to days) than previously thought. PMID- 26262819 TI - Luminescence Solvato- and Vapochromism of Alkynyl-Phosphine Copper Clusters. AB - The reaction of [Cu(NCMe)4][PF6] with aromatic acetylenes HC2R and triphosphine 1,1,1-tris(diphenylphosphino)methane in the presence of NEt3 results in the formation of hexanuclear Cu(I) clusters with the general formula [Cu6(C2R)4{(PPh2)3CH}2][PF6]2 (R = 4-X-C6H4 (1-5) and C5H4N (6); X = NMe2 (1), OMe (2), H (3), Ph (4), CF3 (5)). The structural motif of the complexes studied consists of a Cu6 metal core supported by two phosphine ligands and stabilized by sigma- and pi-coordination of the alkynyl fragments (together with coordination of pyridine nitrogen atoms in cluster 6). The solid state structures of complexes 2-6 were determined by single crystal XRD analysis. The structures of the complexes in solution were elucidated by (1)H, (31)P, (1)H-(1)H COSY NMR spectroscopy, and ESI mass spectrometry. Clusters 1-6 exhibit moderately strong phosphorescence in the solid state with quantum yields up to 17%. Complexes 1-5 were found to form solvates (acetone, acetonitrile) in the solid state. The coordination of loosely bound solvent molecules strongly affects emission characteristics and leads to solvato- and vapochromic behavior of the clusters. Thus, solvent-free and acetonitrile solvated forms of 3 demonstrate contrasting emission in orange (615 nm) and blue (475 nm) regions, respectively. The computational studies show that alkynyl-centered IL transitions mixed with those of MLCT between the Cu6 metal core and the ligand environment play a dominant role in the formation of excited states and can be considerably modulated by weakly coordinating solvent molecules leading to luminescence vapochromism. PMID- 26262818 TI - Deciphering the bat virome catalog to better understand the ecological diversity of bat viruses and the bat origin of emerging infectious diseases. AB - Studies have demonstrated that ~60%-80% of emerging infectious diseases (EIDs) in humans originated from wild life. Bats are natural reservoirs of a large variety of viruses, including many important zoonotic viruses that cause severe diseases in humans and domestic animals. However, the understanding of the viral population and the ecological diversity residing in bat populations is unclear, which complicates the determination of the origins of certain EIDs. Here, using bats as a typical wildlife reservoir model, virome analysis was conducted based on pharyngeal and anal swab samples of 4440 bat individuals of 40 major bat species throughout China. The purpose of this study was to survey the ecological and biological diversities of viruses residing in these bat species, to investigate the presence of potential bat-borne zoonotic viruses and to evaluate the impacts of these viruses on public health. The data obtained in this study revealed an overview of the viral community present in these bat samples. Many novel bat viruses were reported for the first time and some bat viruses closely related to known human or animal pathogens were identified. This genetic evidence provides new clues in the search for the origin or evolution pattern of certain viruses, such as coronaviruses and noroviruses. These data offer meaningful ecological information for predicting and tracing wildlife-originated EIDs. PMID- 26262821 TI - Associations Between Viral and Bacterial Potential Pathogens in the Nasopharynx of Children With and Without Respiratory Symptoms. AB - BACKGROUND: Nasopharyngeal (NP) bacterial colonization is necessary for subsequent respiratory and/or invasive infection. Our study aimed at comparing NP bacterial colonization rates between children with and without symptoms of an acute viral respiratory tract infection and examining associations between identified microorganisms. METHODS: Children 3 months to 6 years of age with and without an acute viral respiratory tract infection were recruited, and a questionnaire was filled. NP samples were examined for Streptococcus pneumoniae (SP), Haemophilus influenzae (HI), Moraxella catarrhalis (MC), Staphylococcus aureus and Streptococcus pyogenes by culture. Viruses were detected with polymerase chain reaction. RESULTS: Median age of the 386 recruited children was 23.4 months, and 127 had no respiratory symptoms. More asymptomatic subjects were found negative for all bacteria tested (P < 0.01). SP (P < 0.01), MC (P = 0.001) and mixed bacterial colonization patterns were more frequent among symptomatic children (P < 0.05). Colonization of symptomatic, virus-positive children with MC was higher than in asymptomatic and/or virus-negative children (P = 0.005). The highest HI and MC colonization rates were recorded in association with influenza virus. A strongly negative association between SP and S. aureus, a higher rate of HI detection among SP colonized children and an increased likelihood of MC detection in the presence of HI were observed. HI colonization was more likely in the presence of respiratory syncytial virus and MC colonization was associated with rhinovirus detection. CONCLUSIONS: Viruses are associated with different NP bacterial colonization patterns. Observed pathogens' associations may play a role in disease, and continuous surveillance is required to follow possible effects of interventions such as vaccines. PMID- 26262822 TI - Bridging the Gap Between Research and Practice: Implementation Science. AB - PURPOSE: This article introduces implementation science, which focuses on research methods that promote the systematic application of research findings to practice. METHOD: The narrative defines implementation science and highlights the importance of moving research along the pipeline from basic science to practice as one way to facilitate evidence-based service delivery. This review identifies challenges in developing and testing interventions in order to achieve widespread adoption in practice settings. A framework for conceptualizing implementation research is provided, including an example to illustrate the application of principles in speech-language pathology. Last, the authors reflect on the status of implementation research in the discipline of communication sciences and disorders. CONCLUSIONS: The extant literature highlights the value of implementation science for reducing the gap between research and practice in our discipline. While having unique principles guiding implementation research, many of the challenges and questions are similar to those facing any investigators who are attempting to design valid and reliable studies. This article is intended to invigorate interest in the uniqueness of implementation science among those pursuing both basic and applied research. In this way, it should help ensure the discipline's knowledge base is realized in practice and policy that affects the lives of individuals with communication disorders. PMID- 26262823 TI - Eyes on New Product Development. PMID- 26262824 TI - Adsorption of Modified Arg, Lys, Asp, and Gln to Dry and Hydrated ZnO Surface: A Density Functional Theory Study. AB - The interface of biological molecules with inorganic surfaces has been the subject of several recent studies. Experimentally some amino acids are evidenced to play a critical role in the adhesion and selectivity on oxide surfaces; however, detailed information on how the water molecules on the hydrated surface are able to mediate the adsorption is still missing. Accurate total energy ab initio calculations based on dispersion-corrected density functional theory have been performed to investigate the adsorption of selected amino acids on the hydrated ZnO(1010) surface, and the results are presented and discussed in this paper. We have also investigated the role played by water in the determination of the most energetically favorable adsorption configurations of the selected amino acids. We have found that for some amino acids the most energetically favorable configurations involve the deprotonation of the molecule if the water screening is not effective. PMID- 26262825 TI - Controlling the Spin Texture of Topological Insulators by Rational Design of Organic Molecules. AB - We present a rational design approach to customize the spin texture of surface states of a topological insulator. This approach relies on the extreme multifunctionality of organic molecules that are used to functionalize the surface of the prototypical topological insulator (TI) Bi2Se3. For the rational design we use theoretical calculations to guide the choice and chemical synthesis of appropriate molecules that customize the spin texture of Bi2Se3. The theoretical predictions are then verified in angular-resolved photoemission experiments. We show that, by tuning the strength of molecule-TI interaction, the surface of the TI can be passivated, the Dirac point can energetically be shifted at will, and Rashba-split quantum-well interface states can be created. These tailored interface properties-passivation, spin-texture tuning, and creation of hybrid interface states-lay a solid foundation for interface-assisted molecular spintronics in spin-textured materials. PMID- 26262826 TI - Roles of prefrontal cortex and paraventricular thalamus in affective and mechanical components of visceral nociception. AB - Visceral pain represents a major clinical challenge in the management of many gastrointestinal disorders, eg, pancreatitis. However, cerebral neurobiological mechanisms underlying visceral nociception are poorly understood. As a representative model of visceral nociception, we applied cerulein hyperstimulation in C57BL6 mice to induce acute pancreatitis and performed a behavioral test battery and c-Fos staining of brains. We observed a specific pain phenotype and a significant increase in c-Fos immunoreactivity in the paraventricular nucleus of the thalamus (PVT), the periaqueductal gray, and the medial prefrontal cortex (mPFC). Using neuronal tracing, we observed projections of the PVT to cortical layers of the mPFC with contacts to inhibitory GABAergic neurons. These inhibitory neurons showed more activation after cerulein treatment suggesting thalamocortical "feedforward inhibition" in visceral nociception. The activity of neurons in pancreatitis-related pain centers was pharmacogenetically modulated by designer receptors exclusively activated by designer drugs, selectively and cell type specifically expressed in target neurons using adeno associated virus-mediated gene transfer. Pharmacogenetic inhibition of PVT but not periaqueductal gray neurons attenuated visceral pain and induced an activation of the descending inhibitory pain pathway. Activation of glutamatergic principle neurons in the mPFC, but not inhibitory neurons, also reversed visceral nociception. These data reveal novel insights into central pain processing that underlies visceral nociception and may trigger the development of novel, potent centrally acting analgesic drugs. PMID- 26262827 TI - Heightened cold pain and pressure pain sensitivity in young female adults with moderate-to-severe menstrual pain. AB - This study investigated the association between menstrual pain severity and psychophysical measures of cold and pressure pain sensitivity. A cross-sectional design was used with young women (n = 432) from the Western Australian Pregnancy Cohort (Raine) Study. Menstrual pain severity and oral contraception use was obtained from questionnaires at 20 and 22-year follow-ups. A visual analog scale (VAS; range from 0 [none] to 10 [unbearable]) was used to measure menstrual pain severity at both 20 and 22 years over the 3-year period, with 3 groups created: (1) no pain or mild pain (VAS 0-3), (2) at least moderate pain at a minimum of 1 of the 2 time points (hereafter named "mixed)", and (3) severe pain (VAS 8-10). Cold pain sensitivity (dorsal wrist) and pressure pain sensitivity (lumbar spine, upper trapezius, dorsal wrist, and tibialis anterior) were assessed using standardised quantitative sensory testing protocols. Confounding variables included number of musculoskeletal pain sites, oral contraceptive use, smoking, physical activity, body mass index, psychological distress, and sleep. Severe menstrual pain and mixed menstrual pain were positively associated with heightened cold pain sensitivity (distant from menstrual pain referral site) and pressure pain sensitivity (local to menstrual pain referral site). These associations remained significant after adjusting for potential confounding variables including multisite musculoskeletal pain. Our findings suggest peripheral and central neurophysiological mechanisms contributing to heightened pain sensitivity in young women with moderate and severe menstrual pain. These data highlight the need for innovative management approaches to attenuate the negative impact of severe menstrual pain in young women. PMID- 26262828 TI - A phase 3, multicenter, randomized, double-blind, placebo-controlled, safety, tolerability, and efficacy study of Xtampza ER in patients with moderate-to severe chronic low back pain. AB - Opioid analgesics are commonly used for the treatment of chronic low back pain (CLBP); however, abuse potential is a major concern. This study used a randomized, double-blind, placebo-controlled, enriched-enrollment randomized withdrawal study design to evaluate the safety, tolerability, and analgesic efficacy of an abuse-deterrent formulation of extended-release oxycodone, Xtampza ER, in opioid-naive and opioid-experienced adults with moderate-to-severe CLBP. Patients entered an open-label titration phase (N = 740); those who were successfully titrated on Xtampza ER (>=40 to <=160 mg oxycodone hydrochloride equivalent per day) were randomized to active drug (N = 193) or placebo (N = 196) for 12 weeks. Primary efficacy results showed a statistically significant difference in average pain intensity from randomization baseline to treatment week 12 between the Xtampza ER and placebo groups (mean [+/-SE], -1.56 [0.267]; P < 0.0001). All sensitivity analyses results supported the primary result of the study. Secondary efficacy outcomes indicated that Xtampza ER vs placebo had more patients with improvement in patient global impression of change (26.4% vs 14.3%; P < 0.0001), longer time-to-exit from the study (58 vs 35 days; P = 0.0102), and a greater proportion of patients with >=30% (49.2% vs 33.2%; P = 0.0013) and >=50% (38.3% vs 24.5%; P = 0.0032) improvement in pain intensity. There was less rescue medication (acetaminophen) use in the Xtampza ER treatment group than in the placebo group. Xtampza ER had an adverse event profile consistent with other opioids and was well tolerated; no new safety concerns were identified. In conclusion, Xtampza ER resulted in clinically and statistically significant efficacy in patients with CLBP. PMID- 26262829 TI - The role of airflow for the relief of chronic refractory breathlessness. AB - PURPOSE OF REVIEW: Chronic refractory breathlessness is a major cause of suffering to people with advanced stage cardiorespiratory and some neurodegenerative diseases. It is a frightening, distressing and disabling symptom that imposes significant burdens on family members. Evidence is mounting for the role of facial or nasal airflow for the relief of chronic refractory breathlessness in those patients with mild hypoxaemia or normoxaemia. Airflow can be delivered from a cylinder of compressed medical air via face mask or nasal cannulae or a hand-held fan. The hand-held fan offers patients a simple, low cost, self-management strategy that is not associated with any known risks. Therefore, it is timely and relevant to review the research available for the efficacy and appropriateness of facial or nasal airflow. RECENT FINDINGS: There is sufficient review evidence available to suggest that airflow from the hand held fan or medical air can provide clinically relevant and discernible relief of chronic refractory breathlessness at rest in patients with advanced diseases. SUMMARY: The hand-held fan should be considered as one of the first interventions to try in management plans for patients who present with mild hypoxaemia or normoxaemia and chronic refractory breathlessness at rest or on minimal exertion. Emerging evidence indicates that airflow from the hand-held fan may also have an important role with exertion-induced breathlessness, decreasing distress and speeding recovery time after exercise, thereby helping patients self-manage their symptoms during everyday general activity and plan for crises of breathlessness, secure in the knowledge that they have a tangible, easily portable device to try in any circumstances. PMID- 26262830 TI - Options in metastatic urothelial cancer after first-line therapy. AB - PURPOSE OF REVIEW: The treatment of patients with metastatic urothelial carcinoma is evolving with recent advances holding promise for improved outcomes. Historically, patients with metastatic urothelial carcinoma had a poor prognosis with no standard treatment options in the second-line setting. Currently, with an increased understanding of the heterogeneity of clinical bladder cancer subtypes and molecular diversity of the disease, there is optimism that outcomes will start to improve. The present review will evaluate historical second-line treatment options and focus on emerging therapies in this setting. RECENT FINDINGS: Single-agent cytotoxic chemotherapy agents continue to be evaluated in patients with metastatic urothelial carcinoma with variable results. Targeted therapies, including tyrosine kinase inhibitors and monoclonal antibodies, have also been extensively evaluated in this disease. Early phase data have as yet failed to demonstrate improvements in survival; however evaluations of targeted agents in enriched patient populations and in combination with chemotherapeutic agents are ongoing. Novel immunotherapeutic approaches have shown encouraging results and are currently being evaluated extensively. SUMMARY: The optimal treatment for patients with metastatic urothelial carcinoma in the second-line setting is unknown. Recent advances in the field gives rise to optimism as the focus shifts to individualization of therapy based on clinical and molecular characteristics of the patient and the disease. PMID- 26262831 TI - Management of bone metastases in prostate cancer: a review. AB - PURPOSE OF REVIEW: Bone metastases in the advanced stages of prostate cancer have a detrimental effect on the quality of life, resulting in skeletal-related events and pain and place a significant burden on healthcare resources. Improvements in prostate cancer treatment have led to a longer survival of patients. Therefore, quality of life is of growing interest and importance. Successful management and prevention of the complications of bone metastasis in those patients remains, however, clinically challenging. RECENT FINDINGS: Recently, radium-223 was approved as a treatment for bone metastasis in patients with prostate cancer, joining zoledronic acid, denosumab and other radiopharmaceuticals in the clinical armamentarium. Radium-223 has shown to improve overall survival in patients with bone metastasis. SUMMARY: This review focuses on the recent landmark studies on zoledronic acid, denosumab and radium-223 for patients with metastatic prostate cancer and gives a comprehensive overview of their mechanism of action, efficacy, dosage and safety profile. PMID- 26262832 TI - Breast cancer and fertility: an update. AB - PURPOSE OF REVIEW: This review will summarize key fertility issues in young women with breast cancer. The detrimental effects of treatment modalities on ovarian and hormonal function will be reviewed. Options for fertility protection and preservation will also be outlined, as well as the unique issues facing women in pregnancy with a previous breast cancer diagnosis. RECENT FINDINGS: Gonadotropin releasing hormone analogues continue to be in debate for their protective impact on the ovaries during the time of gonadotoxic treatment. Success rates in the cryopreservation of embryos, oocytes and gonadal tissue continue to improve. Concurrently, advancing reproductive technologies are developing promising techniques for obtaining mature oocytes from ovarian tissue and from early ovarian follicles. The pursuit of a pregnancy after breast cancer treatment is an additional challenge. Increasing bodies of evidence support the safety of pregnancy after breast cancer and the possibly improved survival. Still, there is an uncertainty regarding recommended intervals from diagnosis to conception. Preimplantation genetic diagnosis for hereditary breast cancer mutations is also becoming of increasing interest. SUMMARY: The fertility impact of breast cancer treatment in young women is of ongoing concern. The effects should be universally addressed and options should be outlined with young women prior to commencement of treatment. PMID- 26262833 TI - Increase in frequency of publication: a new era for PHCR&D. PMID- 26262834 TI - Carbon "Quantum" Dots for Fluorescence Labeling of Cells. AB - The specifically synthesized and selected carbon dots of relatively high fluorescence quantum yields were evaluated in their fluorescence labeling of cells. For the cancer cell lines, the cellular uptake of the carbon dots was generally efficient, resulting in the labeling of the cells with bright fluorescence emissions for both one- and two-photon excitations from predominantly the cell membrane and cytoplasm. In the exploration on labeling the live stem cells, the cellular uptake of the carbon dots was relatively less efficient, though fluorescence emissions could still be adequately detected in the labeled cells, with the emissions again predominantly from the cell membrane and cytoplasm. This combined with the observed more efficient internalization of the same carbon dots by the fixed stem cells might suggest some significant selectivity of the stem cells toward surface functionalities of the carbon dots. The needs and possible strategies for more systematic and comparative studies on the fluorescence labeling of different cells, including especially live stem cells, by carbon dots as a new class of brightly fluorescent probes are discussed. PMID- 26262839 TI - Significant Impact of Immunogen Design on the Diversity of Antibodies Generated by Carbohydrate-Based Anticancer Vaccine. AB - Development of an effective vaccine targeting tumor associated carbohydrate antigens (TACAs) is an appealing approach toward tumor immunotherapy. While much emphasis has been typically placed on generating high antibody titers against the immunizing antigen, the impact of immunogen design on the diversity of TACA specific antibodies elicited has been overlooked. Herein, we report that the immunogen structure can significantly impact the breadth and the magnitude of humoral responses. Vaccine constructs that induced diverse TACA-binding antibodies provided much stronger recognition of a variety of Tn positive tumor cells. Optimization of the breadth of the antibody response led to a vaccine construct that demonstrated long lasting efficacy in a mouse tumor model. After challenged with the highly aggressive TA3Ha cells, mice immunized with the new construct exhibited a statistically significant improvement in survival relative to controls (0% vs 50% survival; p < 0.0001). Furthermore, the surviving mice developed long-term immunity against TA3Ha. Thus, both the magnitude and the breadth of antibody reactivity should be considered when designing TACA-based antitumor vaccines. PMID- 26262840 TI - Moving Toward Patient-Centered Care in Africa: A Discrete Choice Experiment of Preferences for Delivery Care among 3,003 Tanzanian Women. AB - OBJECTIVE: In order to develop patient-centered care we need to know what patients want and how changing socio-demographic factors shape their preferences. METHODS: We fielded a structured questionnaire that included a discrete choice experiment to investigate women's preferences for place of delivery care in four rural districts of Pwani Region, Tanzania. The discrete choice experiment consisted of six attributes: kind treatment by the health worker, health worker medical knowledge, modern equipment and medicines, facility privacy, facility cleanliness, and cost of visit. Each woman received eight choice questions. The influence of potential supply- and demand- side factors on patient preferences was evaluated using mixed logit models. RESULTS: 3,003 women participated in the discrete choice experiment (93% response rate) completing 23,947 choice tasks. The greatest predictor of health facility preference was kind treatment by doctor (beta = 1.13, p<0.001), followed by having a doctor with excellent medical knowledge (beta = 0.89 p<0.001) and modern medical equipment and drugs (beta = 0.66 p<0.001). Preferences for all attributes except kindness and cost were changed with changes to education, primiparity, media exposure and distance to nearest hospital. CONCLUSIONS: Care quality, both technical and interpersonal, was more important than clinic inputs such as equipment and cleanliness. These results suggest that while basic clinic infrastructure is necessary, it is not sufficient for provision of high quality, patient-centered care. There is an urgent need to build an adequate, competent, and kind health workforce to raise facility delivery and promote patient-centered care. PMID- 26262841 TI - Mass-Spectrometry-Based Serum Metabolomics of a C57BL/6J Mouse Model of High-Fat Diet-Induced Non-alcoholic Fatty Liver Disease Development. AB - Obesity, dyslipidemia, insulin resistance, oxidative stress, and inflammation are key clinical risk factors for the progression of non-alcoholic fatty liver disease (NAFLD). Currently, there is no comprehensive metabolic profile of a well established animal model that effectively mimics the etiology and pathogenesis of NAFLD in humans. Here, we report the pathophysiological and metabolomic changes associated with NAFLD development in a C57BL/6J mouse model in which NAFLD was induced by feeding a high-fat diet (HFD) for 4, 8, 12, and 16 weeks. Serum metabolomic analysis was conducted using ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC QTOF-MS) and gas chromatography-mass spectrometry (GC-MS) to establish a metabolomic profile. Analysis of the metabolomic profile in combination with principal component analysis revealed marked differences in metabolites between the control and HFD group depending upon NAFLD severity. A total of 30 potential biomarkers were strongly associated with the development of NAFLD. Among these, 11 metabolites were mainly related to carbohydrate metabolism, hepatic biotransformation, collagen synthesis, and gut microbial metabolism, which are characteristics of obesity, as well as significantly increased serum glucose, total cholesterol, and hepatic triglyceride levels during the onset of NAFLD (4 weeks). At 8 weeks, 5 additional metabolites that are chiefly involved in perturbation of lipid metabolism and insulin secretion were found to be associated with hyperinsulinemia, hyperlipidemia, and hepatic steatosis in the mid-term of NAFLD progression. At the end of 12 and 16 weeks, 14 additional metabolites were predominantly correlated to abnormal bile acid synthesis, oxidative stress, and inflammation, representing hepatic inflammatory infiltration during NAFLD development. These results provide potential biomarkers for early risk assessment of NAFLD and further insights into NAFLD development. PMID- 26262842 TI - Heterogeneous Effects of Direct Hypoxia Pathway Activation in Kidney Cancer. AB - General activation of hypoxia-inducible factor (HIF) pathways is classically associated with adverse prognosis in cancer and has been proposed to contribute to oncogenic drive. In clear cell renal carcinoma (CCRC) HIF pathways are upregulated by inactivation of the von-Hippel-Lindau tumor suppressor. However HIF-1alpha and HIF-2alpha have contrasting effects on experimental tumor progression. To better understand this paradox we examined pan-genomic patterns of HIF DNA binding and associated gene expression in response to manipulation of HIF-1alpha and HIF-2alpha and related the findings to CCRC prognosis. Our findings reveal distinct pan-genomic organization of canonical and non-canonical HIF isoform-specific DNA binding at thousands of sites. Overall associations were observed between HIF-1alpha-specific binding, and genes associated with favorable prognosis and between HIF-2alpha-specific binding and adverse prognosis. However within each isoform-specific set, individual gene associations were heterogeneous in sign and magnitude, suggesting that activation of each HIF-alpha isoform contributes a highly complex mix of pro- and anti-tumorigenic effects. PMID- 26262843 TI - Prostaglandin E2 from Candida albicans Stimulates the Growth of Staphylococcus aureus in Mixed Biofilms. AB - BACKGROUND: Previous studies showed that Staphylococcus aureus and Candida albicans interact synergistically in dual species biofilms resulting in enhanced mortality in animal models. METHODOLOGY/PRINCIPAL FINDINGS: The aim of the current study was to test possible candidate molecules which might mediate this synergistic interaction in an in vitro model of mixed biofilms, such as farnesol, tyrosol and prostaglandin (PG) E2. In mono-microbial and dual biofilms of C.albicans wild type strains PGE2 levels between 25 and 250 pg/mL were measured. Similar concentrations of purified PGE2 significantly enhanced S.aureus biofilm formation in a mode comparable to that observed in dual species biofilms. Supernatants of the null mutant deficient in PGE2 production did not stimulate the proliferation of S.aureus and the addition of the cyclooxygenase inhibitor indomethacin blocked the S.aureus biofilm formation in a dose-dependent manner. Additionally, S. aureus biofilm formation was boosted by low and inhibited by high farnesol concentrations. Supernatants of the farnesol-deficient C. albicans ATCC10231 strain significantly enhanced the biofilm formation of S. aureus but at a lower level than the farnesol producer SC5314. However, C. albicans ATCC10231 also produced PGE2 but amounts were significantly lower compared to SC5314. CONCLUSION/SIGNIFICANCE: In conclision, we identified C. albicans PGE2 as a key molecule stimulating the growth and biofilm formation of S. aureus in dual S. aureus/C. albicans biofilms, although C. albicans derived farnesol, but not tyrosol, may also contribute to this effect but to a lesser extent. PMID- 26262845 TI - Nanoparticle Sizing and Potential Quality Control of Sols Using a Unique Fluorescence Anisotropy Probe and 3D Contour Anisotropy Mapping. AB - Spectroscopic properties of the particle sizing fluorophore Dipole Blue are reported. The probe is cationic in nature, highly water-soluble, and strongly adheres to anionic silica surfaces by electrostatic interactions, as is demonstrated here by Ludox SM 30. The probe has a distinct absorbance band centered at 320 nm, and the fluorescence emission band is Stokes-shifted 100 nm with a peak centered at 426 nm. From time-correlated single-photon counting experiments, the fluorescence lifetime was found to be adequately described by a three-exponential decay model with an intensity-averaged lifetime of 15.6 ns. Perrin graph analysis of steady-state anisotropy shows the presence of silica particles with a radius of (5.44 +/- 0.16) nm, which, considering the distribution of particle sizes, is in reasonable agreement with 3.5 nm found from dynamic light scattering experiments. PMID- 26262844 TI - Copy Number Variation Screen Identifies a Rare De Novo Deletion at Chromosome 15q13.1-13.3 in a Child with Language Impairment. AB - A significant proportion of children (up to 7% in the UK) present with pronounced language difficulties that cannot be explained by obvious causes like other neurological and medical conditions. A substantial genetic component is predicted to underlie such language problems. Copy number variants (CNVs) have been implicated in neurodevelopmental and psychiatric conditions, such as autism and schizophrenia, but it is not fully established to what extent they might contribute to language disorders. We conducted a CNV screen in a longitudinal cohort of young children with language-related difficulties (n = 85), focusing on single events at candidate loci. We detected a de novo deletion on chromosome 15q13.1-13.3. The adjacent 15q11-13.1 locus is disrupted in Prader-Willi and Angelman syndromes, while disruptions across the breakpoints (BP1-BP6) have previously been implicated in different neurodevelopmental phenotypes including autism, intellectual disability (ID), seizures and developmental delay (DD). This is the first report of a deletion at BP3-BP5 being linked to a deficit confined to language impairment, in the absence of ID, expanding the range of phenotypes that implicate the chromosome 15q13 locus. PMID- 26262846 TI - Molecular Weight Determination by Counting Molecules. AB - Molecular weight (MW) is one of the most important characteristics of macromolecules. Sometimes, MW cannot be measured correctly by conventional methods like gel permeation chromatography (GPC) due to, for example, aggregation. We propose using single-molecule spectroscopy to measure the average MW simply by counting individual fluorescent molecules embedded in a thin matrix film at known mass concentration. We tested the method on dye molecules, a labeled protein, and the conjugated polymer MEH-PPV. We showed that GPC with polystyrene calibration overestimates the MW of large MEH-PPV molecules by 40 times due to chain aggregation and stiffness. This is a crucial observation for understanding correlations between the conjugated polymer length, photophysics and performances of devices. The method can measure the MW of fluorescent molecules, biological objects, and nanoparticles at ultimately low concentrations and does not need any reference; it is conformation-independent and has no limitations regarding the detected MW range. PMID- 26262847 TI - Molecular Level Design Principle behind Optimal Sizes of Photosynthetic LH2 Complex: Taming Disorder through Cooperation of Hydrogen Bonding and Quantum Delocalization. AB - The light harvesting 2 (LH2) antenna complex from purple photosynthetic bacteria is an efficient natural excitation energy carrier with well-known symmetric structure, but the molecular level design principle governing its structure function relationship is unknown. Our all-atomistic simulations of nonnatural analogues of LH2 as well as those of a natural LH2 suggest that nonnatural sizes of LH2-like complexes could be built. However, stable and consistent hydrogen bonding (HB) between bacteriochlorophyll and the protein is shown to be possible only near naturally occurring sizes, leading to significantly smaller disorder than for nonnatural ones. Extensive quantum calculations of intercomplex exciton transfer dynamics, sampled for a large set of disorder, reveal that taming the negative effect of disorder through a reliable HB as well as quantum delocalization of the exciton is a critical mechanism that makes LH2 highly functional, which also explains why the natural sizes of LH2 are indeed optimal. PMID- 26262848 TI - Correction to "Emergence of Hysteresis and Transient Ferroelectric Response in Organo-Lead Halide Perovskite Solar Cells". PMID- 26262849 TI - Metal Semiconductor Heterostructures for Photocatalytic Conversion of Light Energy. AB - For fast separation of the photogenerated charge carriers, metal semiconductor heterostructures have emerged as one of the leading materials in recent years. Among these, metal Au coupled with low bandgap semiconductors remain as ideal materials where both can absorb the solar light in the visible region. It is also established that on excitation, the plasmonic state of gold interacts with excited state of semiconductor and helps for the delocalization of the photogenerated electrons. Focusing these materials where electron transfer preferably occurs from semiconductor to metal Au on excitation, in this Perspective, we report the latest developments in the synthetic chemistry in designing such nano heterostructures and discuss their photocatalytic activities in organic dye degradation/reduction and/or photocatalytic water splitting for generation of hydrogen. Among these, materials such as Au-CZTS, Au-SnS, Au-Bi2S3, Au-ZnSe, and so forth are emphasized, and their formation chemistry as well as their photocatalytic activities are discussed in this Perspective. PMID- 26262850 TI - Enhanced-Resolution Single-Shot 2DFT Spectroscopy by Spatial Spectral Interferometry. AB - We demonstrate use of spatial interference for the complete electric field reconstruction of two-dimensional (2D) coherent spectroscopic signals generated through four-wave mixing (4WM) in a single laser shot. Until now, the amplitude and phase characterization of 4WM signals has relied primarily on Fourier transform spectral interferometry (FTSI), which limits the measurement's sensitivity and resolution. We show that spatial spectral interferometry (SSI) is a generalized approach to 4WM signal detection that eliminates these inherent limitations of FTSI without introducing additional experimental complexity. SSI is used to measure the 2D photon echo spectra of two systems with dramatically different line widths, the coupled D line transitions in rubidium vapor and the energy-transfer dynamics in the light-harvesting protein LH2. PMID- 26262851 TI - Recent Development in Hydrogen Evolution Reaction Catalysts and Their Practical Implementation. AB - The past 10 years have seen great advances in the field of electrochemical hydrogen evolution. In particular, several new nonprecious metal electrocatalysts, for example, the MoS2 or the Ni2P family of materials, have emerged as contenders for electrochemical hydrogen evolution under harsh acidic conditions offering nearly platinum-like catalytic performance. The developments have been particularly fast in the last 5 years, and the present Perspective highlights key developments and discusses them, along with hydrogen evolution in general, in the context of the global energy problem. PMID- 26262852 TI - Switching Oxygen Reduction Pathway by Exfoliating Graphitic Carbon Nitride for Enhanced Photocatalytic Phenol Degradation. AB - The selectivity of molecular oxygen activation on the exfoliated graphitic carbon nitride (g-C3N4) and its influence on the photocatalytic phenol degradation process were demonstrated. Compared with bulk g-C3N4, the exfoliated nanosheet yielded a 3-fold enhancement in photocatalytic phenol degradation. ROS trapping experiments demonstrated that although the direct hole oxidation was mainly responsible for phenol photodegradation on both g-C3N4 catalysts, molecular oxygen activation processes on their surface greatly influenced the whole phenol degradation efficiency. Reactive oxygen species and Raman spectroscopy measurements revealed that oxygen was preferentially reduced to .O2(-) by one electron transfer on bulk g-C3N4, while on g-C3N4 nanosheet the production of H2O2 via a two-electron transfer process was favored due to the rapid formation of surface-stabilized 1,4-endoperoxide. The latter process not only promotes the separation of photogenerated electron-hole pairs but also greatly facilitates reactive oxygen species formation and subsequently enhances phenol degradation. PMID- 26262853 TI - Signature Vibrational Bands for Defects in CVD Single-Layer Graphene by Surface Enhanced Raman Spectroscopy. AB - We report the observation of signature vibrational bands in the frequency region between 900 and 1600 cm(-1) for defects in single-layer graphene (SLG) using surface Raman spectroscopy in ultrahigh vacuum. Vapor deposition of Ag leads to the formation of surface nanoparticles that migrate to defects in the SLG, leading to surface-enhanced Raman scattering (SERS) of the graphene G and 2D bands as well as new vibrational modes ascribed to native defects. Many of the new spectral bands of these native defects are similar, although not identical, to those predicted previously for -C2 defects. These new bands are observed in addition to bands more commonly observed for defective graphene that are attributed to the D, G*, D+G, and 2D' modes. The defects observed in these SLG films are not believed to result from the Ag deposition process but are postulated to be formed during the graphene CVD growth process. These defects are then made visible by postdeposition of Ag due to SERS. PMID- 26262854 TI - Surface Enhanced Raman Spectroscopy of Organic Molecules on Magnetite (Fe3O4) Nanoparticles. AB - Surface-enhanced Raman spectroscopy (SERS) of species bound to environmentally relevant oxide nanoparticles is largely limited to organic molecules structurally related to catechol that facilitate a chemical enhancement of the Raman signal. Here, we report that magnetite (Fe3O4) nanoparticles provide a SERS signal from oxalic acid and cysteine via an electric field enhancement. Magnetite thus likely provides an oxide substrate for SERS study of any adsorbed organic molecule. This substrate combines benefits from both metal-based and chemical SERS by providing an oxide surface for studies of environmentally and catalytically relevant detailed chemical bonding information with fewer restrictions of molecular structure or binding mechanisms. Therefore, the magnetite-based SERS demonstrated here provides a new approach to establishing the surface interactions of environmentally relevant organic ligands and mineral surfaces. PMID- 26262855 TI - Toward Economically Feasible Direct Solar-to-Fuel Energy Conversion. PMID- 26262856 TI - Thickness-Dependent Photoelectrochemical Water Splitting on Ultrathin LaFeO3 Films Grown on Nb:SrTiO3. AB - The performance of photoelectrodes can be modified by changing the material chemistry, geometry, and interface engineering. Specifically, nanoscale active layers can facilitate the collection of charge carriers. In heterostructure devices, the multiple material interfaces are particularly important, which at present are not well understood for oxides. Here, we report a detailed study of ultrathin (2-25 nm) LaFeO3 films grown epitaxially on Nb-doped SrTiO3. The films exhibit thickness-dependence with sensitivity to less than 10 nm in both the through-plane charge transfer conductivity and in the potential-dependent photoresponse. Supplementing photoelectrochemical measurements with X-ray photoelectron spectroscopy, spectroscopic ellipsometry, and electrochemical impedance spectroscopy, we construct a band model that accounts for this thickness dependence via a shifting valence-band offset at the film-substrate interface and the potential-dependent overlap of the depletion regions present at both the film-substrate and film-electrolyte interfaces. These results illustrate the utility of using active layer thickness and film-substrate interactions to tune the performance of photoelectrodes, providing insight for the design of efficient heterostructure oxide photoelectrochemical devices. PMID- 26262857 TI - Hydrogen Atom Transfer from Water or Alcohols Activated by Presolvated Electrons. AB - High-energy irradiation of protic solvents can transiently introduce excess electrons that are implicated in a diverse range of reductive processes. Here we report the evolution of electron solvation in water and in alcohols following photodetachment from aqueous hydroxide or the corresponding alkoxides studied by two- and three-pulse femtosecond spectroscopy and ab initio molecular dynamic simulations. The experiments reveal an ultrafast recombination channel of the excess electrons. Through the calculations this channel emerges as an H-atom transfer process to the hydroxyl or alkoxy radical species from neighboring solvent molecules, which are activated as the presolvated electron occupies their antibonding orbitals. The initially low activation barrier in the early stages of electron solvation was found to increase (from 12 to 44 kJ/mol in water) as full solvation proceeded. PMID- 26262858 TI - Linker Length-Dependent Control of Gemini Surfactant Aqueous Lyotropic Gyroid Phase Stability. AB - Network-phase lyotropic liquid crystals (LLCs) derived from the water-directed self-assembly of small molecule amphiphiles comprise a useful class of soft nanomaterials, with wide-ranging applications in structural biology and membrane science. However, few known surfactants enable access to these mesophases over wide temperature and amphiphile concentration phase windows. Recent studies have demonstrated that gemini ("twin tail") dicarboxylate surfactants, in which alkyl carboxylates are covalently linked near the headgroups by a hydrophobic bridge, exhibit increased propensities to form double gyroid network phase LLCs. We demonstrate herein that the lyotropic self-assembly behaviors of gemini dicarboxylates sensitively depend on the linker length, whereby odd-carbon linkers stabilize the double gyroid network LLC over unprecedented amphiphile concentration windows up to ~45 wt % wide between T ~ 22-80 degrees C. These self-assembly phenomena, which arise from the linker length-dependent preferred molecular conformations of these amphiphiles, will broaden the technological applications of these nanostructured LLCs. PMID- 26262859 TI - Spontaneous Fluctuations of Transition Dipole Moment Orientation in OLED Triplet Emitters. AB - The efficiency of an organic light-emitting diode (OLED) depends on the microscopic orientation of transition dipole moments of the molecular emitters. The most effective materials used for light generation have 3-fold symmetry, which prohibits a priori determination of dipole orientation due to the degeneracy of the fundamental transition. Single-molecule spectroscopy reveals that the model triplet emitter tris(1-phenylisoquinoline)iridium(III) (Ir(piq)3) does not behave as a linear dipole, radiating with lower polarization anisotropy than expected. Spontaneous symmetry breaking occurs in the excited state, leading to a random selection of one of the three ligands to form a charge-transfer state with the metal. This nondeterministic localization is revealed in switching of the degree of linear polarization of phosphorescence. Polarization scrambling likely raises out-coupling efficiency and should be taken into account when deriving molecular orientation of the guest emitter within the OLED host from ensemble angular emission profiles. PMID- 26262860 TI - Transition-Path Probability as a Test of Reaction-Coordinate Quality Reveals DNA Hairpin Folding Is a One-Dimensional Diffusive Process. AB - Chemical reactions are typically described in terms of progress along a reaction coordinate. However, the quality of reaction coordinates for describing reaction dynamics is seldom tested experimentally. We applied a framework for gauging reaction-coordinate quality based on transition-path analysis to experimental data for the first time, looking at folding trajectories of single DNA hairpin molecules measured under tension applied by optical tweezers. The conditional probability for being on a reactive transition path was compared with the probability expected for ideal diffusion over a 1D energy landscape based on the committor function. Analyzing measurements and simulations of hairpin folding where end-to-end extension is the reaction coordinate, after accounting for instrumental effects on the analysis, we found good agreement between transition path and committor analyses for model two-state hairpins, demonstrating that folding is well-described by 1D diffusion. This work establishes transition-path analysis as a powerful new tool for testing experimental reaction-coordinate quality. PMID- 26262861 TI - Ammonia-Containing Species Formed in Cu-Chabazite As Per In Situ EPR, Solid-State NMR, and DFT Calculations. AB - Nowadays, the most attractive technology for the elimination of nitric oxides from the exhaust gas of diesel vehicles is the selective catalytic reduction with ammonia (NH3-SCR-NOx) using Cu zeolite with the chabazite structure as the catalyst. Isolated copper species are the active sites, but the reaction intermediates and the overall reaction mechanism are still under debate. Here, we study the interaction of ammonia with zeolite Cu-SSZ-13 (CHA topology) with a uniform distribution of Cu(2+) sites prepared in one pot and a conventional Cu ZSM-5 (MFI topology) for comparison. In situ EPR and solid-state NMR spectroscopies combined with DFT calculations have allowed the identification of NH4(+), [Cu(NH3)5](2+), [Cu(Of)2(NH3)2](2+), [Cu(Of)3NH3](2+), [Cu(NH3)2](+), and [CuOf(NH3)](+) (Of being framework oxygen) under different conditions. The results demonstrate that ammonia is able to reduce Cu(2+) to Cu(+) and provide new information on the species formed in Cu-SSZ-13, which have important implications for the elucidation of the SCR reaction mechanism. PMID- 26262862 TI - A Simple Index for Characterizing Charge Transport in Molecular Materials. AB - While advances in quantum chemistry have rendered the accurate prediction of band alignment relatively straightforward, the ability to forecast a noncrystalline, multimolecule system's conductivity possesses no simple computational form. Adapting the theory of classical resistor networks, we develop an index for quantifying charge transport in bulk molecular materials, without the requirement of crystallinity. The basic behavior of this index is illustrated through its application to simple lattices and clusters of common organic photovoltaic molecules, where it is shown to reproduce experimentally known performances for these materials. This development provides a quantitative computational means for determining a priori the bulk charge transport properties of molecular materials. PMID- 26262863 TI - Surface Effect of Alumina on the First Electronic Transition of Liquid Water Studied by Far-Ultraviolet Spectroscopy. AB - The first electronic transition (A <- X) of liquid water (H2O and D2O) on an alpha-alumina substrate was studied using variable angle attenuated total reflection far-ultraviolet (VA-ATR-FUV) spectroscopy in the wavelength region 140 180 nm (8.86-6.89 eV). A variation in the penetration depth of the evanescent wave of a probe light (25-19 nm) directly determined individual FUV spectra associated with bulk water (distance from the alumina surface >2 nm) and interfacial water (<2 nm). We found that the A <- X band of the interfacial water was markedly blue-shifted and red-tailed relative to the bulk water. The electronic state difference of the interfacial water from the bulk water mainly arose from the hydrogen-bond structure and energy affected by the alumina surface. PMID- 26262864 TI - Liquid-Phase Vibrational Strong Coupling. AB - Light-matter strong coupling involving ground-state molecular vibrations is investigated for the first time in the liquid phase for a set of molecules placed in microcavities. By tuning the cavities, one or more vibrational modes can be coupled in parallel or in series, inducing a change in the vibrational frequencies of the bonds. These findings are of fundamental importance to fully develop light-matter strong coupling for applications in molecular and material sciences. PMID- 26262865 TI - Auger-Limited Carrier Recombination and Relaxation in CdSe Colloidal Quantum Wells. AB - Using time-resolved photoluminescence spectroscopy, we show that two-exciton Auger recombination dominates carrier recombination and cooling dynamics in CdSe nanoplatelets, or colloidal quantum wells. The electron-hole recombination rate depends only on the number of electron-hole pairs present in each nanoplatelet, and is consistent with a two-exciton recombination process over a wide range of exciton densities. The carrier relaxation rate within the conduction and valence bands also depends only on the number of electron-hole pairs present, apart from an initial rapid decay, and is consistent with the cooling rate being limited by reheating due to Auger recombination processes. These Auger-limited recombination and relaxation dynamics are qualitatively different from the carrier dynamics in either colloidal quantum dots or epitaxial quantum wells. PMID- 26262866 TI - Unidirectional Adsorption of Bifunctional 1,4-Phenylene Diisocyanide on the Ge(100)-2 * 1 Surface. AB - Adsorption of bifunctional organic molecules on semiconductor surfaces is important for surface modification; however, most bifunctional molecules previously studied have yielded mixtures of singly and dually tethered adsorbates. Here we report the adsorption of bifunctional 1,4-phenylene diisocyanide (PDI) on the Ge(100)-2 * 1 surface, in which singly bound adsorbates are selectively produced. As shown by polarized multiple internal reflection infrared spectroscopy experiments and density functional theory calculations, PDI adsorbates form a single C-dative bonding configuration through one of the isocyanide functionalities, retaining one unreacted isocyanide moiety per adsorbate. The angle of the molecular axis is ~30 degrees from the surface normal. The delocalized pi* molecular orbital of the free molecule is also preserved upon adsorption. These results demonstrate the potential usefulness of isocyanide adsorbates as a means toward selective organic functionalization of semiconductor surfaces. PMID- 26262867 TI - Utilization of Metal Sulfide Material of (CuGa)(1-x)Zn(2x)S2 Solid Solution with Visible Light Response in Photocatalytic and Photoelectrochemical Solar Water Splitting Systems. AB - Upon forming a solid solution between CuGaS2 and ZnS, we have successfully developed a highly active (CuGa)(1-x)Zn(2x)S2 photocatalyst for H2 evolution in the presence of sacrificial reagents under visible light irradiation. The Ru loaded (CuGa)0.8Zn0.4S2 functioned as a H2-evolving photocatalyst in a Z-scheme system with BiVO4 of an O2-evolving photocatalyst and Co complexes of an electron mediator. The Z-scheme system split water into H2 and O2 under visible light and simulated sunlight irradiation. The (CuGa)(1-x)Zn(2x)S2 possessed a p-type semiconductor character. The photoelectrochemical cell with a Ru-loaded (CuGa)0.5ZnS2 photocathode and a CoO(x)-modified BiVO4 photoanode split water even without applying an external bias. Thus, we successfully demonstrated that the metal sulfide material group can be available for Z-scheme and electrochemical systems to achieve solar water splitting into H2 and O2. PMID- 26262868 TI - Probing Magnetism in 2D Molecular Networks after in Situ Metalation by Transition Metal Atoms. AB - Metalated molecules are the ideal building blocks for the bottom-up fabrication of, e.g., two-dimensional arrays of magnetic particles for spintronics applications. Compared to chemical synthesis, metalation after network formation by an atom beam can yield a higher degree of control and flexibility and allows for mixing of different types of magnetic atoms. We report on successful metalation of tetrapyridyl-porphyrins (TPyP) by Co and Cr atoms, as demonstrated by scanning tunneling microscopy experiments. For the metalation, large periodic networks formed by the TPyP molecules on a Ag(111) substrate are exposed in situ to an atom beam. Voltage-induced dehydrogenation experiments support the conclusion that the porphyrin macrocycle of the TPyP molecule incorporates one transition metal atom. The newly synthesized Co-TPyP and Cr-TPyP complexes exhibit striking differences in their electronic behavior, leading to a magnetic character for Cr-TPyP only as evidenced by Kondo resonance measurements. PMID- 26262869 TI - First-Principles Calculations of the Energy and Width of the (2)A(u) Shape Resonance in p-Benzoquinone: A Gateway State for Electron Transfer. AB - Quinones are versatile biological electron acceptors and mobile electron carriers in redox processes. We present the first ab initio calculations of the width of the (2)A(u) shape resonance in the para-benzoquinone anion, the simplest member of the quinone family. This resonance state located at 2.5 eV above the ground state of the anion is believed to be a gateway state for electron attachment in redox processes involving quinones. We employ the equation-of-motion coupled cluster method for electron affinity augmented by a complex-absorbing potential (CAP-EOM-EA-CCSD) to calculate the resonance position and width. The calculated width, 0.013 eV, is in excellent agreement with the width of the resonant peak in the photodetachment spectrum, thus supporting the assignment of the band to resonance excitation to the autodetaching (2)A(u) state. The methodological aspects of CAP-EOM-EA-CCSD calculations of resonances positions and widths in medium-sized molecules, such as basis set and CAP box size effects, are also discussed. PMID- 26262870 TI - Ab Initio Study of the Dielectric and Electronic Properties of Multilayer GaS Films. AB - The dielectric properties of multilayer GaS films have been investigated using a Berry phase method and a density functional perturbation theory approach. A linear relationship has been observed between the number of GaS layers and slab polarizability, which can be easily converged at a small supercell size and has a weak correlation with different stacking orders. Moreover, the intercoupling effect of the stacking pattern and applied vertical field on the electronic properties of GaS bilayers has been discussed. The band gaps of different stacking orders show various downward trends with the increasing field, which is interpreted as giant Stark effect. Our study demonstrates that the slab polarizability as the substitution of conventional dielectric constant can act as an independent and reliable parameter to elucidate the dielectric properties of low-dimensional systems and that the applied electric field is an effective method to modulate the electric properties of nanostructures. PMID- 26262871 TI - Loss of Linear Band Dispersion and Trigonal Structure in Silicene on Ir(111). AB - The structure of silicene/Ir(111) was examined on the basis of density functional theory. We have found that Ir(111) preserves the 2D character of silicene but significantly distorts its structure from the trigonal one expected for an isolated silicene. The electronic structure of silicene is strongly hybridized with that of Ir(111) so that silicene on Ir(111) loses its linear band dispersion around the Fermi level, giving rise to a metallic band structure; however, silicene/Ir(111) exhibits a hidden linear-dispersive band, which is related to the linear-dispersive conduction band of an isolated silicene. PMID- 26262872 TI - Solution Synthesized p-Type Copper Gallium Oxide Nanoplates as Hole Transport Layer for Organic Photovoltaic Devices. AB - p-Type metal-oxide hole transport layer (HTL) suppresses recombination at the anode and hence improves the organic photovoltaic (OPV) device performance. While NiOx has been shown to exhibit good HTL performance, very thin films (<10 nm) are needed due to its poor conductivity and high absorption. To overcome these limitations, we utilize CuGaO2, a p-type transparent conducting oxide, as HTL for OPV devices. Pure delafossite phase CuGaO2 nanoplates are synthesized via microwave-assisted hydrothermal reaction in a significantly shorter reaction time compared to via conventional heating. A thick CuGaO2 HTL (~280 nm) in poly(3 hexylthiophene):[6,6]-phenyl-C61-butyric acid methyl ester (P3HT:PCBM) devices achieves 3.2% power conversion efficiency, on par with devices made with standard HTL materials. Such a thick CuGaO2 HTL is more compatible with large-area and high-volume printing process. PMID- 26262873 TI - Shedding Light on the Dock-Lock Mechanism in Amyloid Fibril Growth Using Markov State Models. AB - We investigate how the molecular mechanism of monomer addition to a growing amyloid fibril of the transthyretin TTR105-115 peptide is affected by pH. Using Markov state models to extract equilibrium and dynamical information from extensive all atom simulations allowed us to characterize both productive pathways in monomer addition as well as several off-pathway trapped states. We found that multiple pathways result in successful addition. All productive pathways are driven by the central hydrophobic residues in the peptide. Furthermore, we show that the slowest transitions in the system involve trapped configurations, that is, long-lived metastable states. These traps dominate the rate of fibril growth. Changing the pH essentially reweights the system, leading to clear differences in the relative importance of both productive paths and traps, yet retains the core mechanism. PMID- 26262874 TI - Computational Screening of 2D Materials for Photocatalysis. AB - Two-dimensional (2D) materials exhibit a range of extraordinary electronic, optical, and mechanical properties different from their bulk counterparts with potential applications for 2D materials emerging in energy storage and conversion technologies. In this Perspective, we summarize the recent developments in the field of solar water splitting using 2D materials and review a computational screening approach to rapidly and efficiently discover more 2D materials that possess properties suitable for solar water splitting. Computational tools based on density-functional theory can predict the intrinsic properties of potential photocatalyst such as their electronic properties, optical absorbance, and solubility in aqueous solutions. Computational tools enable the exploration of possible routes to enhance the photocatalytic activity of 2D materials by use of mechanical strain, bias potential, doping, and pH. We discuss future research directions and needed method developments for the computational design and optimization of 2D materials for photocatalysis. PMID- 26262875 TI - Two Different Serum MiRNA Signatures Correlate with the Clinical Outcome and Histological Subtype in Pleural Malignant Mesothelioma Patients. AB - Pleural malignant mesothelioma (MPM) is a detrimental neoplasm affecting pleural sheets and determining a high rate of mortality. In this study, we have enrolled 14 consecutive patients (13 males and 1 female) with MPM (mean age: 70.3 +/- 4.6 years). We have collected serum for the determination of a miRNA profiling using a low-density microarray real time PCR system in the serum of patients and comparing it with that one of 10 control counterparts affected by not-cancer related pleural effusions. In the patients 5 miRNAs were up-regulated (miR101, miR25, miR26b, miR335 and miR433), 2 miRNA were downregulated (miR191, miR223) and two miRNAs were expressed exclusively in patients (miR29a and miR516). Based upon the changes in the expression of the above mentioned miRNAs we detected two distinctive miRNA signatures predicting histotype and survival in these patients: I) patients with more than 3/9 upregulated miRNAs or 3/9 upregulated miRNAs and miR516 not recordable or unchanged (signature A); II) patients with at least 3/9 downregulated or unchanged miRNAs and/or miR29a downregulated (signature B). Based upon these criteria, 5 patients were stratified in signature A and the remaining 9 in signature B. Patients with signature A had a significant shorter median survival than those with signature B (7 months vs. 17 months, 95% CI: 0.098-1.72, p = 0.0021), had a sarcomatoid or mixed histological MPM subtype and were diagnosed in stage II (3/5) and stage III (2/5). In conclusion, we suggest that miRNA signature A is predictive of sarcomatoid histotype and of worse prognosis in MPM. PMID- 26262876 TI - Landscapes for Energy and Wildlife: Conservation Prioritization for Golden Eagles across Large Spatial Scales. AB - Proactive conservation planning for species requires the identification of important spatial attributes across ecologically relevant scales in a model-based framework. However, it is often difficult to develop predictive models, as the explanatory data required for model development across regional management scales is rarely available. Golden eagles are a large-ranging predator of conservation concern in the United States that may be negatively affected by wind energy development. Thus, identifying landscapes least likely to pose conflict between eagles and wind development via shared space prior to development will be critical for conserving populations in the face of imposing development. We used publically available data on golden eagle nests to generate predictive models of golden eagle nesting sites in Wyoming, USA, using a suite of environmental and anthropogenic variables. By overlaying predictive models of golden eagle nesting habitat with wind energy resource maps, we highlight areas of potential conflict among eagle nesting habitat and wind development. However, our results suggest that wind potential and the relative probability of golden eagle nesting are not necessarily spatially correlated. Indeed, the majority of our sample frame includes areas with disparate predictions between suitable nesting habitat and potential for developing wind energy resources. Map predictions cannot replace on the-ground monitoring for potential risk of wind turbines on wildlife populations, though they provide industry and managers a useful framework to first assess potential development. PMID- 26262877 TI - Extracellular Matrix Stiffness Regulates Osteogenic Differentiation through MAPK Activation. AB - Mesenchymal stem cell (MSC) differentiation is regulated by the extracellular matrix (ECM) through activation of intracellular signaling mediators. The stiffness of the ECM was shown to be an important regulatory factor for MSC differentiation, and transcriptional coactivator with PDZ-binding motif (TAZ) was identified as an effector protein for MSC differentiation. However, the detailed underlying mechanism regarding the role of ECM stiffness and TAZ in MSC differentiation is not yet fully understood. In this report, we showed that ECM stiffness regulates MSC fate through ERK or JNK activation. Specifically, a stiff hydrogel matrix stimulates osteogenic differentiation concomitant with increased nuclear localization of TAZ, but inhibits adipogenic differentiation. ERK and JNK activity was significantly increased in cells cultured on a stiff hydrogel. TAZ activation was induced by ERK or JNK activation on a stiff hydrogel because exposure to an ERK or JNK inhibitor significantly decreased the nuclear localization of TAZ, indicating that ECM stiffness-induced ERK or JNK activation is important for TAZ-driven osteogenic differentiation. Taken together, these results suggest that ECM stiffness regulates MSC differentiation through ERK or JNK activation. PMID- 26262878 TI - Developmental Trajectories of Internally and Externally Driven Temporal Prediction. AB - The ability to generate temporal prediction (TP) is fundamental to our survival since it allows us to selectively orient our attention in time in order to prioritize relevant environmental information. Studies on adult participants showed that externally and internally driven mechanisms can be engaged to establish TP, both resulting in better behavioural performance. However, few studies on children have investigated the ability to engage internally and externally driven TP, especially in relation to how these mechanisms change across development. In this study, 111 participants (88 children between six and eleven years of age, and 23 adults) were tested by means of a simple reaction time paradigm, in which temporal cueing and neutral conditions were orthogonally manipulated to induce externally and internally driven TP mechanisms, as well as an interaction between the two. Sequential effects (SEs) relative to both tasks were also investigated. Results showed that all children participating in the study were able to implement both external and internal TP in an independent fashion. However, children younger than eight years were not able to combine both strategies. Furthermore, in the temporal cueing blocks they did not show the typically-observed asymmetric SE pattern. These results suggest that children can flexibly use both external and internal TP mechanisms to optimise their behaviour, although their successful combined use develops only after eight years of age. PMID- 26262879 TI - Unilateral and Bilateral Cortical Resection: Effects on Spike-Wave Discharges in a Genetic Absence Epilepsy Model. AB - RESEARCH QUESTION: Recent discoveries have challenged the traditional view that the thalamus is the primary source driving spike-and-wave discharges (SWDs). At odds, SWDs in genetic absence models have a cortical focal origin in the deep layers of the perioral region of the somatosensory cortex. The present study examines the effect of unilateral and bilateral surgical resection of the assumed focal cortical region on the occurrence of SWDs in anesthetized WAG/Rij rats, a well described and validated genetic absence model. METHODS: Male WAG/Rij rats were used: 9 in the resected and 6 in the control group. EEG recordings were made before and after craniectomy, after unilateral and after bilateral removal of the focal region. RESULTS: SWDs decreased after unilateral cortical resection, while SWDs were no longer noticed after bilateral resection. This was also the case when the resected areas were restricted to layers I-IV with layers V and VI intact. CONCLUSIONS: These results suggest that SWDs are completely abolished after bilateral removal of the focal region, most likely by interference with an intracortical columnar circuit. The evidence suggests that absence epilepsy is a network type of epilepsy since interference with only the local cortical network abolishes all seizures. PMID- 26262881 TI - Alirocumab (Praluent) to lower LDL-Cholesterol. PMID- 26262880 TI - Increased Risk of Acute Pancreatitis in Patients with Rheumatoid Arthritis: A Population-Based Cohort Study. AB - The study was conducted to determine whether patients with rheumatoid arthritis (RA) are at increased risk of acute pancreatitis compared with those without RA and to determine if the risk of acute pancreatitis varied by anti-RA drug use. We used the large population-based dataset from the National Health Insurance (NHI) program in Taiwan to conduct a retrospective cohort study. Patients newly diagnosed with RA between 2000 and 2011 were referred to as the RA group. The comparator non-RA group was matched with propensity score, using age and sex, in the same time period. We presented the incidence density by 100,000 person-years. The propensity score and all variables were analyzed in fully adjusted Cox proportional hazard regression. The cumulative incidence of acute pancreatitis was assessed by Kaplan-Meier analysis, with significance based on the log-rank test. From claims data of one million enrollees randomly sampled from the Taiwan NHI database, 29,755 adults with RA were identified and 119,020 non-RA persons were matched as a comparison group. The RA cohort had higher incidence density of acute pancreatitis (185.7 versus 119.0 per 100,000 person-years) than the non-RA cohort. The adjusted hazard ratio (HR) was 1.62 (95% CI [confidence interval] 1.43-1.83) for patients with RA to develop acute pancreatitis. Oral corticosteroid use decreased the risk of acute pancreatitis (adjusted HR 0.83, 95% CI 0.73-0.94) but without a dose-dependent effect. Current use of disease modifying anti-rheumatic drugs or tumor necrosis factor blockers did not decrease the risk of acute pancreatitis. In conclusion, patients with RA are at an elevated risk of acute pancreatitis. Use of oral corticosteroids may reduce the risk of acute pancreatitis. PMID- 26262882 TI - Palbociclib (Ibrance) for metastatic breast cancer. PMID- 26262883 TI - Brexpiprazole (Rexulti) for schizophrenia and depression. PMID- 26262884 TI - Panobinostat (Farydak) for multiple myeloma. PMID- 26262885 TI - Lenvatinib (Lenvima) for thyroid cancer. PMID- 26262886 TI - Host-targeting agents for treatment of hepatitis B virus infection. AB - Hepatitis B virus (HBV) infection is a major cause of chronic liver disease, including liver cirrhosis, liver failure and hepatocellular carcinoma (HCC)-the second leading and fastest rising cause of cancer death world-wide. While de novo infection can be efficiently prevented by vaccination and chronic infection can be controlled using antivirals targeting the viral polymerase, the development of efficient antiviral strategies to eliminate the virus and thus to cure infection remains a key unmet medical need. The recent progress in the development of robust infectious HBV cell culture models now enables the investigation of the full viral life cycle, including a more detailed study of the molecular mechanisms of virus-host interactions responsible for viral persistence. The understanding of these virus-host interactions will be instrumental for the development of curative treatments. Host-dependency factors have recently emerged as promising candidates to treat and prevent infection by various pathogens. This review focuses on the potential of host-targeting agents (HTAs) as novel antivirals to treat and cure HBV infection. These include HTAs that inhibit de novo and re-infection, synthesis and spread of cccDNA as well as development of immune-based approaches eliminating or curing infected hepatocytes, including the eradication of viral cccDNA. PMID- 26262887 TI - Protective effect of N-acetylcysteine on cyclophosphamide-induced cardiotoxicity in rats. AB - Cyclophosphamide (CP) is an oxazaphosphorine nitrogen mustard alkylating drug used for the treatment of chronic and acute leukemias, lymphoma, myeloma, and cancers of the breast and ovary. It is known to cause severe cardiac toxicity. This study investigated the protective effect of N-Acetylcysteine (NAC) on CP induced cardiotoxicity in rats. CP resulted in a significant increase in serum aminotransferases, creatine kinase (CK), lactate dehydrogenase(LDH) enzymes, asymmetric dimethylarginine and tumor necrosis factor-alpha and significant decrease in total nitrate/nitrite(NOx). In cardiac tissues, a single dose of CP (200mg/kg, i.p.) resulted in significant increase in malondialdehyde and NOx and a significant decrease in reduced glutathione content, glutathione peroxidase, catalase, and superoxide dismutase activities. Interestingly, Administration of NAC (200mg/kg, i.p.) for 5 days prior to CP attenuates all the biochemical changes induced by CP. These results revealed that NAC attenuates CP-induced cardiotoxicity by inhibiting oxidative and nitrosative stress and preserving the activity of antioxidant enzymes. PMID- 26262888 TI - Novel monogenic diseases causing human autoimmunity. AB - Fuelled by the on-going sequencing revolution, the last two years have seen a number of exciting discoveries relating to monogenic disorders predisposing to autoimmunity that provide new insights into the function of the human immune system. Here we discuss a selection of these diseases due to mutations in PRKCD, CTLA4, STAT3, IFIH1, TMEM173 and COPA. PMID- 26262890 TI - Positioning the arts for intervention design research in the human services. AB - The arts have been integral to the human experience fostering innovation in social arrangements, strengthening group cohesion, and merging esthetics with the utilitarian properties of technology. For intervention design research in the human services the arts can harness innovation and creativity in meeting human needs and addressing social issues. Given their capacities to stimulate expression of first person experience through interpretative strategies, the arts can equip people and groups, including researchers, with opportunities to express primary experiential knowledge through creative means, portray useful ways of meeting human needs, educate others about the social issues people experience, and formulate intervention strategies or even models to address the causes and consequences of those issues. In this paper, the authors discuss how the arts can inform and deepen human service intervention design and development and, as a result, advance innovation in the human services. They offer a rationale supporting the inclusion of the arts in the design of human service interventions, examine the contributions of the arts to the formulation of intervention concept and developmental research to further improve interventions, and consider how the arts can advance the reflexivity of intervention designers. The authors draw implications for how researchers can position the arts in the nine steps of intervention design and development the authors offer in this paper. PMID- 26262891 TI - Noncovalent Binding of Polycyclic Aromatic Hydrocarbons with Genetic Bases Reducing the in Vitro Lateral Transfer of Antibiotic Resistant Genes. AB - In current studies of noncovalent interactions of polycyclic aromatic hydrocarbons (PAHs) with genetic units, the impact of such interactions on gene transfer has not been explored. In this study, we examined the association of some widely occurring PAHs (phenanthrene, pyrene, benzo[g,h,i]perylene, and other congeners) with antibiotic resistant plasmids (pUC19). Small molecular PAHs (e.g., phenanthrene) bind effectively with plasmids to form a loosely clew-like plasmid-PAH complex (16.5-49.5 nm), resulting in reduced transformation of ampicillin resistance gene (Ampr). The in vitro transcription analysis demonstrated that reduced transformation of Ampr in plasmids results from the PAH inhibited Ampr transcription to RNA. Fluorescence microtitration coupled with Fourier transform infrared spectroscopy (FTIR) and theoretical interaction models showed that adenine in plasmid has a stronger capacity to sequester small Phen and Pyre molecules via a pi-pi attraction. Changes in Gibbs free energy (DeltaG) suggest that the CT-PAH model reliably depicts the plasmid-PAH interaction through a noncovalently physical sorption mechanism. Considering the wide occurrence of PAHs and antibiotic resistant genes (ARGs) in the environment, our findings suggest that small-sized PAHs can well affect the behavior of ARGs via above-described noncovalent interactions. PMID- 26262889 TI - Estimating PMTCT's Impact on Heterosexual HIV Transmission: A Mathematical Modeling Analysis. AB - INTRODUCTION: Prevention of mother-to-child HIV transmission (PMTCT) strategies include combined short-course antiretrovirals during pregnancy (Option A), triple drug antiretroviral treament (ART) during pregnancy and breastfeeding (Option B), or lifelong ART (Option B+). The WHO also recommends ART for HIV treatment and prevention of sexual transmission of HIV. The impact of PMTCT strategies on prevention of sexual HIV transmission of HIV is not known. We estimated the population-level impact of PMTCT interventions on heterosexual HIV transmission in southwestern Uganda and KwaZulu-Natal, South Africa, two regions with different HIV prevalence and fertility rates. MATERIALS AND METHODS: We constructed and validated dynamic, stochastic, network-based HIV transmission models for each region. PMTCT Options A, B, and B+ were simulated over ten years under three scenarios: 1) current ART and PMTCT coverage, 2) current ART and high PMTCT coverage, and 3) high ART and PMTCT coverage. We compared adult HIV incidence after ten years of each intervention to Option A (and current ART) at current coverage. RESULTS: At current coverage, Options B and B+ reduced heterosexual HIV incidence by about 5% and 15%, respectively, in both countries. With current ART and high PMTCT coverage, Option B+ reduced HIV incidence by 35% in Uganda and 19% in South Africa, while Option B had smaller, but meaningful, reductions. The greatest reductions in HIV incidence were achieved with high ART and PMTCT coverage. In this scenario, all PMTCT strategies yielded similar results. DISCUSSION: Implementation of Options B/B+ reduces adult HIV incidence, with greater effect (relative to Option A at current levels) in Uganda than South Africa. These results are likely driven by Uganda's higher fertility rates. PMID- 26262892 TI - (Me)L2Zn2(MU-1,6-Ph2-N6) - a building block for new hexazene complexes. AB - The zinc hexazene complex (Me)L2Zn2(MU-1,6-Ph2-N6) 1 ((Me)L = HC[C(Me)N(2,4,6 Me3C6H2)]2) is a suitable hexazene transfer reagent in reactions with main group metal and transition metal complexes containing M-Me units. The reactions proceed with elimination of (Me)LZnMe and the resulting complexes were characterized by NMR and IR spectroscopy and single crystal X-ray diffraction (5, 8). Quantum chemical calculations were performed to investigate the electronic structure of 5' and 8' in more detail and to identify the absorption bands of the hexazene unit. PMID- 26262894 TI - Osmotically Driven Deformation of a Stable Water Film. AB - An aspect of dynamic colloidal interactions that has received little attention is the osmotic stress associated with nonequilibrium distribution of solutes. Recent experiments on a mercury drop near a mica surface show a dimple forming on the mercury/water interface when there is a sudden change in the electric potential of the mercury drop coated with a self-assembled monolayer (SAM) of 11-mercapto-1 undecanoic acid thiol molecules. A reasonable hypothesis is that the dimple formation is due to the desorption of a fraction of the SAM from the mercury drop surface when the surface potential is changed. The osmotic pressure in the thin film region increases as a result of the presence of the thiol molecules in the region, giving rise to the observed dimple. A model including the effects of osmotic flow, disjoining pressure, interfacial tension and hydrodynamic pressure is developed to test the hypothesis. The simplest version of the model, in which desorption is uniform and instantaneous, can produce a dimple whose growth is significantly more rapid than its decay, in qualitative agreement with the data. However, quantitative agreement is lacking. Several refinements to the model, including effects such as the change in interfacial tension as thiols are desorbed, gradual thiol desorption, a change in disjoining pressure as charged thiols are desorbed and nonuniform desorption do not change the qualitative picture. The qualitative success of the model suggests the osmotic pressure mechanism is correct, but the detailed picture of the SAM desorption at positive mercury surface potentials is not sufficiently well understood. The model reveals that the osmotic dimple is not the time-reverse equivalent of the usual hydrodynamic dimple phenomenon. We suggest that transient deformation of thin films by osmotic flow is a new and little-studied mechanism influencing the structure of stable thin films and the interaction of deformable drops. This has implications for colloidal interactions in a broader range of systems where solute concentration may not be homogeneous, for example in solute transfer processes. PMID- 26262893 TI - Polymorphism of DNA Methyltransferase 3b and Association with Development and Prognosis in Gastric Cancer. AB - OBJECTIVE: DNA methyltransferase 3b (DNMT3b) plays an important role in abnormal methylation during tumorigenesis. Polymorphism of the DNMT3b gene may influence DNMT3b activity and be associated with cancer risk. This study aimed to investigate the association between single nucleotide polymorphisms (SNPs) of the DNMT3b gene and susceptibility and prognosis of gastric cancer. METHODS: Four hundred and forty-seven histologically-confirmed gastric cancer cases, 111 gastric atrophy cases and 961 tumor-free controls were enrolled into the study. Five tag SNPs (rs6119954, rs1569686, rs4911107, rs4911259 and rs8118663) of the DNMT3b gene were genotyped by TaqMan assay. DNMT3b expression was evaluated in 104 cancer tissues by immunohistochemistry method. RESULTS: The median follow-up time for 422 gastric patients with prognosis information was 55.1 (51.8-58.5) month. We found that individuals with the rs1569686 variant genotype (TG/GG) were significantly associated with poor prognosis in gastric cancer compared to those carrying the TT genotype (HR = 1.43, 95%CI: 1.02-1.99). This trend was more evident in the long-term survival of gastric cancer. Similar results were observed for the G allele carriers of rs4911107 and T allele carriers of rs4911259 as these two sites were in complete linkage disequilibrium with rs1569686. The rs8118663 GG carriers tended to live shorter than AA/AG genotype (HR = 2.72, 95%CI: 1.45-5.12) in patients living longer than 2.0 years. None of the five SNPs was associated with the risks of gastric cancer or gastric atrophy. And no relationship was found between each of the five SNPs and DNMT3b expression. CONCLUSIONS: This study provides evidence that DNMT3b polymorphisms may predict long-term survival of gastric cancer. However, further studies are needed to reveal the underlying biological roles of DNMT3b polymorphism. PMID- 26262895 TI - Tuning the Chirality of Block Copolymers: From Twisted Morphologies to Nanospheres by Self-Assembly. AB - New advances into the chirality effect in the self-assembly of block copolymers (BCPs) have been achieved by tuning the helicity of the chiral-core-forming blocks. The chiral BCPs {[N=P(R)-O2C20H12](200-x)[N=P(OC5H4N)2](x)}-b-[N=PMePh]50 ((R)-O2C20H12 = (R)-1,1'-binaphthyl-2,2'-dioxy, OC5H4N = 4-pyridinoxy (OPy); x = 10, 30, 60, 100 for 3 a-d, respectively), in which the [N=P(OPy)2] units are randomly distributed within the chiral block, have been synthesised. The chiroptical properties of the BCPs ([alpha]D vs. T and CD) demonstrated that the helicity of the BCP chains may be simply controlled by the relative proportion of the chiral and achiral (i.e., [N=P(R)-O2C20H12] and [N=P(OPy)2], respectively) units. Thus, although 3 a only contained only 5% [N=P(OPy)2] units and exhibited a preferential helical sense, 3 d with 50% of this unit adopted non-preferred helical conformations. This gradual variation of the helicity allowed us to examine the chirality effect on the self-assembly of chiral and helical BCPs (i.e., 3 a-c) and chiral but non-helical BCPs (i.e., 3 d). The very significant influence of the helicity on the self-assembly of these materials resulted in a variety of morphologies that extend from helical nanostructures to pearl-necklace aggregates and nanospheres (i.e., 3 b and 3 d, respectively). We also demonstrate that the presence of pyridine moieties in BCPs 3 a-d allows specific decoration with gold nanoparticles. PMID- 26262897 TI - Subsurface pressure profiling: a novel mathematical paradigm for computing colony pressures on substrate during fungal infections. AB - Colony expansion is an essential feature of fungal infections. Although mechanisms that regulate hyphal forces on the substrate during expansion have been reported previously, there is a critical need of a methodology that can compute the pressure profiles exerted by fungi on substrates during expansion; this will facilitate the validation of therapeutic efficacy of novel antifungals. Here, we introduce an analytical decoding method based on Biot's incremental stress model, which was used to map the pressure distribution from an expanding mycelium of a popular plant pathogen, Aspergillus parasiticus. Using our recently developed Quantitative acoustic contrast tomography (Q-ACT) we detected that the mycelial growth on the solid agar created multiple surface and subsurface wrinkles with varying wavelengths across the depth of substrate that were computable with acousto-ultrasonic waves between 50 MHz-175 MHz. We derive here the fundamental correlation between these wrinkle wavelengths and the pressure distribution on the colony subsurface. Using our correlation we show that A. parasiticus can exert pressure as high as 300 KPa on the surface of a standard agar growth medium. The study provides a novel mathematical foundation for quantifying fungal pressures on substrate during hyphal invasions under normal and pathophysiological growth conditions. PMID- 26262896 TI - Prenatal Docosahexaenoic Acid Supplementation and Offspring Development at 18 Months: Randomized Controlled Trial. AB - OBJECTIVE: We evaluated the effects of prenatal docosahexaenoic acid (DHA) supplementation on offspring development at 18 months of age. DESIGN: Randomized placebo double-blind controlled trial. SETTINGS: Cuernavaca, Mexico. PARTICIPANTS AND METHODS: We followed up offspring (n = 730; 75% of the birth cohort) of women in Mexico who participated in a trial of DHA supplementation during the latter half of pregnancy. We assessed the effect of the intervention on child development and the potential modifying effects of gravidity, gender, SES, and quality of the home environment. INTERVENTIONS OR MAIN EXPOSURES: 400 mg/day of algal DHA. OUTCOME MEASURES: Child development at 18 months of age measured using the Spanish version of the Bayley Scales of Infant Development-II. We calculated standardized psychomotor and mental development indices, and behavior rating scale scores. RESULTS: Intent-to-treat differences (DHA-control) were: Psychomotor Developmental Index -0.90 (95% CI: -2.35, 0.56), Mental Developmental Index -0.26 (95% CI: -1.63, 1.10) and Behavior Rating Scale -0.01 (95% CI: -0.95, 0.94). Prenatal DHA intake attenuated the positive association between home environment and psychomotor development index observed in the control group (p for interaction = 0.03) suggesting potential benefits for children living in home environments characterized by reduced caregiver interactions and opportunities for early childhood stimulation. CONCLUSIONS: Prenatal DHA supplementation in a population with low intakes of DHA had no effects on offspring development at 18 months of age although there may be some benefit for infants from poor quality home environments. TRIAL REGISTRATION: Clinicaltrials.gov NCT00646360. PMID- 26262898 TI - Quantifying, Visualizing, and Monitoring Lead Optimization. AB - Although lead optimization (LO) is by definition a process, process-centric analysis and visualization of this important phase of pharmaceutical R&D has been lacking. Here we describe a simple statistical framework to quantify and visualize the progression of LO projects so that the vital signs of LO convergence can be monitored. We refer to the resulting visualizations generated by our methodology as the "LO telemetry" of a project. These visualizations can be automated to provide objective, holistic, and instantaneous analysis and communication of LO progression. This enhances the ability of project teams to more effectively drive LO process, while enabling management to better coordinate and prioritize LO projects. We present the telemetry of five LO projects comprising different biological targets and different project outcomes, including clinical compound selection, termination due to preclinical safety/tox, and termination due to lack of tractability. We demonstrate that LO progression is accurately captured by the telemetry. We also present metrics to quantify LO efficiency and tractability. PMID- 26262899 TI - Plasmonic Moon: A Fano-Like Approach for Squeezing the Magnetic Field in the Infrared. AB - Outstanding results have been achieved in the localization of optical electric fields via ultrasmall plasmonic cavities, paving the way to the subdiffractive confinement of local electromagnetic fields. However, due to the intrinsic constraints related to conventional architectures, no comparable squeezing factors have been managed yet for the magnetic counterpart of radiation, practically hindering the detection and manipulation of magneto-optical effects at the nanoscale. Here, we observe a strong magnetic field nanofocusing in the infrared, promoted by the induction of a coil-type Fano resonance. By triggering the coil current via a quadrupole-like plasmonic mode, we straightforwardly boost the enhancement of the infrared magnetic field and perform its efficient squeezing in localized nanovolumes. PMID- 26262900 TI - INDUCED ABORTIONS IN PAKISTAN: EXPOSITIONS, DESTINATIONS AND REPERCUSSIONS. A QUALITATIVE DESCRIPTIVE STUDY IN RAWALPINDI DISTRICT. AB - Over 2 million abortions occur annually in Pakistan, mostly in a clandestine and unsafe environment. This is an area of grave concern for the reproductive health of women. A dearth of credible data and incomplete information make the problem more difficult to address. This qualitative study was conducted in semi-urban settings in Pakistan to record perceptions and practices concerning care seeking, experiences and outcomes regarding induced abortions and post-abortion care services. Women who had had induced abortions and abortion service providers were interviewed. Unwanted pregnancies and poverty were found to be the main reasons for seeking an abortion. Moreover, the unwanted pregnancies occurred due to low use of contraceptives, mainly due to a fear or past experience of their side effects, unfamiliarity with correct usage and perceived inefficacy of the methods, especially condoms. There is an obvious need for practical and innovative interventions to address unmet need for birth spacing through improved access to contraceptives. Contraceptive providers should be provided with up-to date and detailed training in family planning counselling, and perhaps allowed unrestricted provision of contraceptives. As a long-term measure, improvement in access to education and formal schooling could increase young girls' and women's knowledge of the benefits of family planning and the risks of unsafe abortion practices. Males must be involved in all the initiatives so that both partners are in agreement on correct and consistent contraceptive use. PMID- 26262901 TI - From the Editor-in-Chief's Desk. PMID- 26262902 TI - Pharmacogenetic Study of Serotonin Transporter and 5HT2A Genotypes in Autism. AB - OBJECTIVE: The purpose of this study was to determine whether polymorphisms in the serotonin transporter (SLC6A4) and serotonin-2A receptor (HTR2A) genes are associated with response to escitalopram in patients with autism spectrum disorder (ASD). METHODS: Forty-four participants with ASD were enrolled in a 6 week, forced titration, open label examination of the selective serotonin reuptake inhibitor (SSRI) escitalopram. Doses increased at weekly intervals starting at 2.5mg daily with a maximum possible dose of 20 mg daily achieved by the end of the study. If adverse events were experienced, participants subsequently received the previously tolerated dose for the duration of study. SLC6A4 (5-HTTLPR) and HTR2A (rs7997012) genotype groups were assessed in relation to treatment outcomes and drug doses. RESULTS: Insistence on sameness and irritability symptoms significantly improved over the course of the 6 week treatment period (p<0.0001) in this open-label trial. There were no significant differences observed in the rate of symptom improvement over time across genotype groups. Similarly, dosing trajectory was not significantly associated with genotype groups. CONCLUSIONS: Previous studies have identified SLC6A4 and HTR2A associations with SSRI response in patients with depression and 5-HTTLPR (SLC6A4) associations with escitalopram response in ASD. We did not observe evidence for similar relationships in this ASD study. PMID- 26262904 TI - Gender Differences in the Behavioral Symptoms and Neuropsychological Performance of Patients with Attention-Deficit/Hyperactivity Disorder Treated with Methylphenidate: A Two-Year Follow-up Study. AB - OBJECTIVE: This study investigated the gender differences in behavioral symptoms, as rated by various informants, and in neuropsychological performance, among patients with attention-deficit/hyperactivity disorder (ADHD) treated with methylphenidate during 24 months in a clinical setting. METHODS: Study participants comprised 128 boys (mean age: 13.2+/-2.4 years) and 26 girls (mean age: 12.8+/-1.0 years) with ADHD. All patients were prescribed short-acting oral methylphenidate, taken two or three times daily; each dose ranged between 0.3 and 1.0 mg/kg. At the baseline and 6, 12, 18, and 24 months later, behavioral symptoms were evaluated using the parent and teacher forms of the Swanson, Nolan, and Pelham Version IV (SNAP-IV) scale for ADHD and the ADHD Rating Scale (completed by a child psychiatrist). In addition, neuropsychological function was assessed using the Test of Variables of Attention (TOVA) at each interval. RESULTS: Although both the boys and girls exhibited a significant decrease in the ADHD symptoms observed by parents and clinicians, the girls improved more than the boys did. Based on the teacher reports, neither the boys nor the girls exhibited significant decreases in ADHD symptoms. The symptoms rated by teachers were more severe in the boys than in the girls throughout the first 12 months; however, the gender difference lessened after 12 months. Based on the TOVA assessment, a composite score (containing response time, response time variability, and ADHD score obtained using the TOVA) did not indicate differences between genders. However, another composite score (containing omission errors, commission errors, and response sensitivity) suggested significant improvement only in the boys. CONCLUSIONS: The results suggested that according to a longitudinal follow-up, behavioral and neuropsychological changes among patients with ADHD might differ between genders. Gathering multidimensional information from patients with ADHD is essential in determining how gender modifies the functional outcome of ADHD. PMID- 26262903 TI - Tolerability, Safety, and Benefits of Risperidone in Children and Adolescents with Autism: 21-Month Follow-up After 8-Week Placebo-Controlled Trial. AB - OBJECTIVE: Risperidone has demonstrated efficacy for acute (8 week) and intermediate length (6 month) management of severe irritability and aggression in children and adolescents with autism. Less is known about the long-term effects of risperidone exposure in this population. We examined the tolerability, safety, and therapeutic benefit of risperidone exposure over a 1-2 year follow-up period. METHODS: In a naturalistic study, 84 children and adolescents 5-17 years of age (from an original sample of 101) were assessed an average of 21.4 months after initial entry into a placebo-controlled 8 week trial of risperidone for children and adolescents with autism and severe irritability. They were assessed at baseline and at follow-up on safety and tolerability measures (blood, urinalysis, electrocardiogram [ECG], medical history, vital signs, neurological symptoms, other adverse events), developmental measures (adaptive behavior, intelligence quotient [IQ]), and standardized rating instruments. Treatment over the follow-up period, after completion of protocol participation, was uncontrolled. Statistical analyses assessed outcome over time with or without prolonged risperidone therapy. RESULTS: Two-thirds of the 84 subjects continued to receive risperidone (mean 2.47 mg/day, S.D. 1.29 mg). At follow-up, risperidone was associated with more enuresis, more excessive appetite, and more weight gain, but not more adverse neurological effects. No clinically significant events were noted on blood counts, chemistries, urinalysis, ECG, or interim medical history. Regardless of drug condition at follow-up, there was considerable improvement in maladaptive behavior compared with baseline, including core symptoms associated with autism. Height and weight gains were elevated with risperidone. Social skills on Vineland Adaptive Behavior Scale (VABS) improved with risperidone. Parent-rated Aberrant Behavior Checklist (ABC) Irritability subscale scores were reduced in those taking risperidone at follow-up. Several other measures of maladaptive behavior (some related to socialization) also showed improved functioning in association with risperidone on the ABC or on the Modified Real Life Rating Scale. CONCLUSIONS: Increased appetite, weight gain, and enuresis are risks associated with long-term risperidone. Our data suggest that these risks were balanced by longer-term behavioral and social benefits for many children over 1.8 years of ongoing treatment. PMID- 26262906 TI - Posttraumatic Stress Disorder in a Child with Autism Spectrum Disorder: Challenges in Management. PMID- 26262905 TI - Adverse Events in Very Young Children Prescribed Psychotropic Medications: Preliminary Findings from an Acute Clinical Sample. AB - OBJECTIVE: The present study used the Pediatric Adverse Events Rating Scale (PAERS) to provide a systematic assessment of adverse events (AEs) related to psychotropic medication use in a clinical sample of young children attending a specialized, early childhood partial hospital program. Study goals were as follows: 1) To describe the frequency and types of specific psychotropic medication-related AEs experienced by very young children (ages 3-7 years) in an acute clinical sample, and 2) to identify the psychotropic medication(s) and/or class(es) associated with the highest frequency of AEs. METHODS: Participants were 158 children (118 males; ages 36-95 months, mean=66 months, SD=14.6 months) who presented to a hospital-based day treatment program for young children with severe emotional and behavioral problems, and were prescribed a psychotropic medication at any point during the hospitalization. Data on AEs related to psychotropic medication were collected using the PAERS from 2011 to 2014. RESULTS: The percentages of children who experienced one or more AEs attributed to a psychiatric medication ranged from 0 (sertraline, melatonin) to 41.2% (fluoxetine), with wide variability in the types AEs reported. The overall frequencies of events caused by a stimulant were similar across the two medications examined (21.4% and 27.7% for mixed amphetamine salts and methylphenidate, respectively), with mood-related difficulties and decreased appetite being the most common AEs reported. The frequencies of AEs caused by an alpha agonist were also similar across the two medications examined (9.8% and 17.2% for guanfacine and clonidine, respectively), with fatigue as the most commonly reported AE. With respect to the selective serotonin reuptake inhibitor (SSRI) class, there was a trend for fluoxetine to be associated with more AEs (41.2%) than sertraline (for which no AEs were reported). The most common AEs reported for fluoxetine were impulsivity and poor concentration. CONCLUSIONS: The data presented here support existing literature reporting differences in AEs between age groups. More rigorous studies are warranted to further examine the types and frequencies of AEs related to psychotropic medications in very young children. PMID- 26262907 TI - Motor Weakness Related to Risperidone. PMID- 26262908 TI - Reliability of Volumetry and Perimetry to Assess Knee Volume. AB - CONTEXT: The treatment of edema after a knee injury is usually 1 of the main objectives during rehabilitation. To assess the success of treatment, 2 methods are commonly used in clinical practice: volumetry and perimetry. OBJECTIVE: To investigate the intra- and interassessor reliability of volumetry and perimetry to assess knee volume. DESIGN: Cross-sectional. SETTING: Laboratory. PARTICIPANTS: 45 healthy participants (26 women) with mean age of 22.4 +/- 2.8 y. MAIN OUTCOME MEASURES: Knee volume was assessed by 3 assessors (A, B, and C) with 3 methods (lower-limb volumetry [LLV], knee volumetry [KV], and knee perimetry [KP]). Assessor A was the most-experienced assessor, and assessor C, the least experienced. LLV and KV were performed with participants in the orthostatic position, while KP was performed with participants in supine. RESULTS: For the interassessor analysis, the ICC2,1 was high (.82) for KV and very high for LLV (.99) and KP (.99). For the intra-assessor analysis, ICC2,1 ranged from moderate to high for KV (.69-.83) and was very high for LLV (.99) and KP (.97-.99). CONCLUSION: KV, LLV, and KP are reliable methods, both intra- and interassessor, to measure knee volume. PMID- 26262909 TI - Interventions for leg cramps in pregnancy. AB - BACKGROUND: Leg cramps are a common problem in pregnancy. Various interventions have been used to treat them, including drug, electrolyte and vitamin therapies, and non-drug therapies. OBJECTIVES: To assess the effectiveness and safety of different interventions for treating leg cramps in pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Register (31 March 2015) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) of any intervention (drug, electrolyte, vitamin or non drug therapies) for treatment of leg cramps in pregnancy compared with placebo, no treatment or other treatment. Quinine was excluded for its known adverse effects (teratogenicity). Cluster-RCTS were considered for inclusion. Quasi-RCTs and cross-over studies were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: We included six studies (390 women). Four trials compared oral magnesium with placebo/no treatment, two compared oral calcium with no treatment, one compared oral vitamin B versus no treatment, and one compared oral calcium with oral vitamin C. Two of the trials were well-conducted and reported, the other four had design limitations. The process of random allocation was sub-optimal in three studies, and blinding was not attempted in two. Outcomes were reported in different ways, precluding the use of meta-analysis and limiting the strength of our conclusions.The 'no treatment' group in one four-arm trial has been used as the comparison group for the composite outcome (intensity and frequency of leg cramps) in magnesium, calcium, and vitamin B versus no treatment. This gives it disproportionate weight in the overall analysis, thus interpretation of these results should be cautious. Oral magnesium versus placebo/no treatmentMagnesium (taken orally for two to four weeks) did not consistently reduce the frequency of leg cramps compared with placebo or no treatment. Outcomes that showed differences were: frequency of leg cramps after treatment: never, and twice a week (risk ratio (RR) 5.66, 95% confidence interval (CI) 1.35 to 23.68, one trial, 69 women, evidence graded low; RR 0.29, 95% CI 0.11 to 0.80, one trial, 69 women), and frequency of leg cramps: 50% reduction in number of leg cramps after treatment (RR 1.42, 95% CI 1.09 to 1.86, one trial, 86 women, evidence graded low). The outcomes that showed no difference were: frequency of leg cramps during two weeks of treatment (mean difference (MD) 1.80, 95% CI -1.32 to 4.92, one trial, 38 women, evidence graded low); frequency of leg cramps after treatment: daily, every other day, and once a week (RR 1.20, 95% CI 0.45 to 3.21, one trial, 69 women; RR 0.44, 95% CI 0.12 to 1.57, one trial, 69 women; RR 1.54, 95% CI 0.62 to 3.87, one trial, 69 women).Evidence about whether magnesium supplements reduced the intensity of pain was inconclusive, with two studies showing that it may slightly reduce pain, while one showed no difference. There were no differences in the experience of side effects (including nausea, flatulence, diarrhoea and intestinal air) between pregnant women receiving magnesium compared with placebo/no treatment. Oral calcium versus no treatmentA greater proportion of women receiving calcium supplements experienced no leg cramps after treatment than those receiving no treatment (frequency of leg cramps after treatment: never RR 8.59, 95% CI 1.19 to 62.07, one study, 43 women, evidence graded very low). There was no difference between groups for a composite outcome (intensity and frequency) for partial improvement (RR 0.64, 95% CI 0.36 to 1.15, one trial, 42 women); however, the same trial showed a greater proportion of women experiencing no leg cramps after treatment with calcium compared with no treatment (RR 5.50, 95% CI 1.38 to 21.86).Other secondary outcomes, including side effects, were not reported. Oral vitamin B versus no treatment Frequency of leg cramps was not reported in the one included trial. According to a composite outcome (frequency and intensity), more women receiving vitamin B fully recovered compared with those receiving no treatment (RR 7.50, 95% CI 1.95 to 28.81). Those women receiving no treatment were more likely to experience a partial improvement in the intensity and frequency of leg cramps than those taking vitamin B (RR 0.29, 95% CI 0.11 to 0.73, one trial, 42 women), or to see no change in their condition. However, these results are based on one small study with design limitations.Other secondary outcomes, including side effects, were not reported. Oral calcium versus oral vitamin CThere was no difference in the frequency of leg cramps after treatment with calcium versus vitamin C (RR 1.33, 95% CI 0.53 to 3.38, one study, 60 women, evidence graded very low). Other outcomes, includingside effects, were not reported. AUTHORS' CONCLUSIONS: It is unclear from the evidence reviewed whether any of the interventions (oral magnesium, oral calcium, oral vitamin B or oral vitamin C) provide an effective treatment for leg cramps. This is primarily due to outcomes being measured and reported in different, incomparable ways, and design limitations compromising the quality of the evidence (the level of evidence was graded low or very low). This was mainly due to poor study design and trials being too small to address the question satisfactorily.Adverse outcomes were not reported, other than side effects for magnesium versus placebo/no treatment. It is therefore not possible to assess the safety of these interventions.The inconsistency in the measurement and reporting of outcomes, meant that data could not be pooled, meta-analyses could not be carried out, and comparisons between studies are difficult.The review only identified trials of oral interventions (magnesium, calcium, vitamin B or vitamin C) to treat leg cramps in pregnancy. None of the trials considered non-drug therapies, for example, muscle stretching, massage, relaxation, heat therapy, and dorsiflexion of the foot. This limits the completeness and applicability of the evidence.Standardised measures for assessing the frequency, intensity and duration of leg cramps to be used in large well-conducted randomised controlled trials are needed to answer this question. Trials of non-drug therapies are also needed. PMID- 26262910 TI - Adjusting the Metrics of 1-D Helical Gold Nanoparticle Superstructures Using Multivalent Peptide Conjugates. AB - The properties of nanoparticle superstructures depend on many factors, including the structural metrics of the nanoparticle superstructure (particle diameter, interparticle distances, etc.). Here, we introduce a family of gold-binding peptide conjugate molecules that can direct nanoparticle assembly, and we describe how these molecules can be systematically modified to adjust the structural metrics of linear double-helical nanoparticle superstructures. Twelve new peptide conjugates are prepared via linking a gold-binding peptide, AYSSGAPPMPPF (PEP(Au)), to a hydrophobic aliphatic tail. The peptide conjugates have 1, 2, or 3 PEP(Au) headgroups and a C12, C14, C16, or C18 aliphatic tail. The soft assembly of these peptide conjugates was studied using transmission electron microscopy (TEM), atomic force microscopy (AFM), and infrared (IR) spectroscopy. Several peptide conjugates assemble into 1-D twisted fibers having measurable structural parameters such as fiber width, thickness, and pitch that can be systematically varied by adjusting the aliphatic tail length and number of peptide headgroups. The linear soft assemblies serve as structural scaffolds for arranging gold nanoparticles into double-helical superstructures, which are examined via TEM. The pitch and interparticle distances of the gold nanoparticle double helices correspond to the underlying metrics of the peptide conjugate soft assemblies, illustrating that designed peptide conjugate molecules can be used to not only direct the assembly of gold nanoparticles but also control the metrics of the assembled structure. PMID- 26262911 TI - Outcomes of a Multimodal Resilience Training Program in an Outpatient Integrative Medicine Clinic. AB - OBJECTIVE: To investigate the outcomes of resilience training (RT) in an outpatient clinical setting on symptom relief for current or recurrent depression, as well as perceived stress and state and trait anxiety. DESIGN: Observational effectiveness study. SETTINGS/LOCATION: Penny George Institute for Health and Healing, Allina Health, Minneapolis, MN. PARTICIPANTS: A total of 728 men and women age 18 years and older who participated in the RT program between December 1, 2007, and November 31, 2012. Of these individuals, 371 were considered study contributors and completed at least one questionnaire both before (pre-RT) and after (post-RT) completion of the program. The remaining participants were considered study non-contributors and did not complete any questionnaires. INTERVENTIONS: RT is a mindfulness-based program that synergizes elements of mindfulness meditation with nutrition and exercise into a cohesive intervention. OUTCOME MEASURES: Depressive symptoms, as well as state and trait anxiety and perceived stress. RESULTS: Among the 371 RT participant contributors, depressive symptoms, perceived stress, and state and trait anxiety improved significantly from pre-RT to post-RT. Furthermore, among participants with depression at baseline, Center for Epidemiologic Studies Depression Scale-10 scores decreased by a mean of 44.0% (from 17.5 to 9.8), a value below the cutoff for significant depressive symptoms. Baseline perceived stress scores were the most predictive of program success. CONCLUSIONS: This study provides evidence that a multimodal RT program delivered in a real-world clinical setting improves symptoms of depression, anxiety, and stress. Limitations of this effectiveness study include a homogeneous population of mostly white women and a large amount of randomized, imputed, and missing data. Future work should include a randomized controlled trial and potentially studies to separate RT into the three components to determine which may be primarily responsible for the improved outcomes. PMID- 26262913 TI - Engineering Transcriptional Regulator Effector Specificity Using Computational Design and In Vitro Rapid Prototyping: Developing a Vanillin Sensor. AB - The pursuit of circuits and metabolic pathways of increasing complexity and robustness in synthetic biology will require engineering new regulatory tools. Feedback control based on relevant molecules, including toxic intermediates and environmental signals, would enable genetic circuits to react appropriately to changing conditions. In this work, variants of qacR, a tetR family repressor, were generated by computational protein design and screened in a cell-free transcription-translation (TX-TL) system for responsiveness to a new targeted effector. The modified repressors target vanillin, a growth-inhibiting small molecule found in lignocellulosic hydrolysates and other industrial processes. Promising candidates from the in vitro screen were further characterized in vitro and in vivo in a gene circuit. The screen yielded two qacR mutants that respond to vanillin both in vitro and in vivo. While the mutants exhibit some toxicity to cells, presumably due to off-target effects, they are prime starting points for directed evolution toward vanillin sensors with the specifications required for use in a dynamic control loop. We believe this process, a combination of the generation of variants coupled with in vitro screening, can serve as a framework for designing new sensors for other target compounds. PMID- 26262914 TI - Oral Hygiene And Heart Disease? PMID- 26262912 TI - A taxonomy of behaviour change methods: an Intervention Mapping approach. AB - In this paper, we introduce the Intervention Mapping (IM) taxonomy of behaviour change methods and its potential to be developed into a coding taxonomy. That is, although IM and its taxonomy of behaviour change methods are not in fact new, because IM was originally developed as a tool for intervention development, this potential was not immediately apparent. Second, in explaining the IM taxonomy and defining the relevant constructs, we call attention to the existence of parameters for effectiveness of methods, and explicate the related distinction between theory-based methods and practical applications and the probability that poor translation of methods may lead to erroneous conclusions as to method effectiveness. Third, we recommend a minimal set of intervention characteristics that may be reported when intervention descriptions and evaluations are published. Specifying these characteristics can greatly enhance the quality of our meta-analyses and other literature syntheses. In conclusion, the dynamics of behaviour change are such that any taxonomy of methods of behaviour change needs to acknowledge the importance of, and provide instruments for dealing with, three conditions for effectiveness for behaviour change methods. For a behaviour change method to be effective: (1) it must target a determinant that predicts behaviour; (2) it must be able to change that determinant; (3) it must be translated into a practical application in a way that preserves the parameters for effectiveness and fits with the target population, culture, and context. Thus, taxonomies of methods of behaviour change must distinguish the specific determinants that are targeted, practical, specific applications, and the theory-based methods they embody. In addition, taxonomies should acknowledge that the lists of behaviour change methods will be used by, and should be used by, intervention developers. Ideally, the taxonomy should be readily usable for this goal; but alternatively, it should be clear how the information in the taxonomy can be used in practice. The IM taxonomy satisfies these requirements, and it would be beneficial if other taxonomies would be extended to also meet these needs. PMID- 26262915 TI - Proposed Dietary Guidelines 2015 and Implications for Cardiovascular Disease and Diabetes. PMID- 26262916 TI - Successful Mentoring Relationships: American Heart Association Council on Cardiovascular and Stroke Nursing. PMID- 26262917 TI - Event centrality prospectively predicts PTSD symptoms. AB - BACKGROUND: Recent evidence suggests that event centrality has a prominent association with post-traumatic stress disorder (PTSD) symptoms. However, evidence for this notion thus far has been mostly correlational. We report two studies that prospectively examined the relationship between event centrality and PTSD symptoms. Study 1 METHODS: Participants (N = 1438) reported their most stressful event ("prior event"), along with event centrality, PTSD symptoms, and neuroticism. At Time 2 participants reported their most stressful event since Time 1 ("critical event"), along with measures of event centrality and PTSD symptoms. Study 1 RESULTS: Event centrality for the critical event predicted PTSD symptoms, after controlling for event centrality and PTSD symptoms of the prior event and neuroticism. Study 2 METHODS: In the second study (N = 161) we examined changes in event centrality and PTSD symptoms over a month. Study 2 RESULTS: Using a cross-lagged panel design, results revealed event centrality at Time 1 significantly predicted PTSD symptoms at Time 2, but the reverse was not significant. CONCLUSIONS: In two studies, a prospective association between event centrality and PTSD symptoms, but not the reverse, emerged. This evidence implicates event centrality in the pathogenesis and/or maintenance of PTSD symptoms. PMID- 26262919 TI - "Be free, be everywhere, be forever.". PMID- 26262918 TI - Movement-related activity during goal-directed hand actions in the monkey ventrolateral prefrontal cortex. AB - Grasping actions require the integration of two neural processes, one enabling the transformation of object properties into corresponding motor acts, and the other involved in planning and controlling action execution on the basis of contextual information. The first process relies on parieto-premotor circuits, whereas the second is considered to be a prefrontal function. Up to now, the prefrontal cortex has been mainly investigated with conditional visuomotor tasks requiring a learned association between cues and behavioural output. To clarify the functional role of the prefrontal cortex in grasping actions, we recorded the activity of ventrolateral prefrontal (VLPF) neurons while monkeys (Macaca mulatta) performed tasks requiring reaching-grasping actions in different contextual conditions (in light and darkness, memory-guided, and in the absence of abstract learned rules). The results showed that the VLPF cortex contains neurons that are active during action execution (movement-related neurons). Some of them showed grip selectivity, and some also responded to object presentation. Most movement-related neurons discharged during action execution both with and without visual feedback, and this discharge typically did not change when the action was performed with object mnemonic information and in the absence of abstract rules. The findings of this study indicate that a population of VLPF neurons play a role in controlling goal-directed grasping actions in several contexts. This control is probably exerted within a wider network, involving parietal and premotor regions, where the role of VLPF movement-related neurons would be that of activating, on the basis of contextual information, the representation of the motor goal of the intended action (taking possession of an object) during action planning and execution. PMID- 26262920 TI - A Challenging Cutaneous T-Cell Lymphoma. AB - Cutaneous peripheral T-cell lymphomas not otherwise specified (CPTL-NOS) are rare neoplasms accounting for just 2% of cutaneous peripheral T-cell lymphomas (CPTL). Only very few case series have been reported. They represent a phenotypically and prognostically heterogenous group of CPTL that do not fit into any of CPTL well defined subtypes. The authors report a case of a 64-year-old man with simultaneous plaque-like lesions and disseminated nodules growing rapidly on the face, trunk, and extremities over a 6-month period. There was no a history of preceding patches, erythematous plaques, rash, or pruritic lesions. These lesions were extending over 80% of the skin surface. Histopathologic analysis revealed dense diffuse infiltrates composed of mostly medium-sized to large lymphoid cells throughout the entire dermis without epidermotropism. Neoplastic cells were atypical with markedly pleomorphic nuclei. Immunohistochemistry showed that the tumor cells were positive for CD3, CD4, and CD5 with a loss of CD7. They were negative for CD20, CD8, CD56, CXCL13, PD1, TIA-1, granzyme-B, perforin, CD25, and CD30. The proliferative fraction was low, with MIB-1 labeling less than 10% of cells. The authors diagnosed the patient with primary CPTL-NOS. Despite the rarity of these tumors, clinicians as well as dermatopathologists and pathologists should be familiar with these rare CPTL especially because most of these lymphomas have an aggressive behavior and exhibit an unfavorable prognosis. PMID- 26262921 TI - Frequency of hypopigmented mycosis fungoides in Egyptian patients presenting with hypopigmented lesions of the trunk. AB - Hypopigmented mycosis fungoides (HMF) is an uncommon variant of mycosis fungoides with an unknown exact frequency. We aimed to study the frequency of HMF in a cohort of Egyptian patients presenting to a tertiary care center in Cairo, Egypt, with hypopigmented lesions of the trunk. Hundred patients with hypopigmented lesions involving the trunk (with or without other sites involvement) were subjected to thorough clinical and histopathological examination. Immunohistochemical studies (S100, CD4, and CD8) were performed when indicated. Constellation of findings was used to reach a final diagnosis. Sixteen cases had HMF (16%). Other than HMF, our cohort included hypopigmented parapsoriasis en plaque (42 cases), postinflammatory hypopigmentation (28 cases), progressive macular hypomelanosis (12 cases), and pityriasis alba (2 cases). In comparison with other hypopigmented disorders, HMF was significantly associated with progressive disease course (P = 0.004), affection of distal upper limbs (P = 0.005), proximal lower limbs (P = 0.003), large-sized lesions (>5 cm) (P < 0.0001), well-defined margin (P < 0.0001), scaliness (P = 0.002), erythema (P < 0.0001), atrophy (P = 0.012), and mottled pigmentation (P < 0.0001). Awareness of HMF and its characteristic clinical features is mandatory to avoid underdiagnosis or overdiagnosis with subsequent morbidity or unnecessary aggressive therapy, respectively. PMID- 26262922 TI - Heart Rate Variability Density Analysis (Dyx) and Prediction of Long-Term Mortality after Acute Myocardial Infarction. AB - AIMS: The density HRV parameter Dyx is a new heart rate variability (HRV) measure based on multipole analysis of the Poincare plot obtained from RR interval time series, deriving information from both the time and frequency domain. Preliminary results have suggested that the parameter may provide new predictive information on mortality in survivors of acute myocardial infarction (MI). This study compares the prognostic significance of Dyx to that of traditional linear and nonlinear measures of HRV. METHODS AND RESULTS: In the Nordic ICD pilot study, patients with an acute MI were screened with 2D echocardiography and 24-hour Holter recordings. The study was designed to assess the power of several HRV measures to predict mortality. Dyx was tested in a subset of 206 consecutive Danish patients with analysable Holter recordings. After a median follow-up of 8.5 years 70 patients had died. Of all traditional and multipole HRV parameters, reduced Dyx was the most powerful predictor of all-cause mortality (HR 2.4; CI 1.5 to 3.8; P < 0.001). After adjustment for known risk markers, such as age, diabetes, ejection fraction, previous MI and hypertension, Dyx remained an independent predictor of mortality (P = 0.02). Reduced Dyx also predicted cardiovascular death (P < 0.01) and sudden cardiovascular death (P = 0.05). In Kaplan-Meier analysis, Dyx significantly predicted mortality in patients both with and without impaired left ventricular systolic function (P < 0.0001). CONCLUSION: The new nonlinear HRV measure Dyx is a promising independent predictor of mortality in a long-term follow-up study of patients surviving a MI, irrespectively of left ventricular systolic function. PMID- 26262923 TI - La6Ba3[Si17N29O2]Cl-An Oxonitridosilicate Chloride with Exceptional Structural Motifs. AB - The oxonitridosilicate chloride La6Ba3[Si17N29O2]Cl was synthesized by a high temperature reaction in a radiofrequency furnace starting from LaCl3, BaH2, and the ammonolysis product of Si2Cl6. Diffraction data of a micrometer-sized single crystal were obtained using microfocused synchrotron radiation at beamline ID11 of the ESRF. EDX measurements on the same crystal confirm the chemical composition. The crystal structure [space group P63/m (no. 176), a = 9.8117(14), c = 19.286(6) A, Z = 2] contains an unprecedented interrupted three-dimensional network of vertex-sharing SiN4 and SiN3O tetrahedra. The SiN4 tetrahedra form dreier rings. Twenty of the latter condense in a way that the Si atoms form icosahedra. Each icosahedron is connected to others via six SiN4 tetrahedra that are part of dreier rings and via six Q(3)-type SiN3O tetrahedra. Rietveld refinements confirm that the final product contains only a small amount of impurities. Lattice energy (MAPLE) and bond-valence sum (BVS) calculations show that the structure is electrostatically well balanced. Infrared spectroscopy confirms the absence of N-H bonds. PMID- 26262924 TI - Single-neuron activity and eye movements during human REM sleep and awake vision. AB - Are rapid eye movements (REMs) in sleep associated with visual-like activity, as during wakefulness? Here we examine single-unit activities (n=2,057) and intracranial electroencephalography across the human medial temporal lobe (MTL) and neocortex during sleep and wakefulness, and during visual stimulation with fixation. During sleep and wakefulness, REM onsets are associated with distinct intracranial potentials, reminiscent of ponto-geniculate-occipital waves. Individual neurons, especially in the MTL, exhibit reduced firing rates before REMs as well as transient increases in firing rate immediately after, similar to activity patterns observed upon image presentation during fixation without eye movements. Moreover, the selectivity of individual units is correlated with their response latency, such that units activated after a small number of images or REMs exhibit delayed increases in firing rates. Finally, the phase of theta oscillations is similarly reset following REMs in sleep and wakefulness, and after controlled visual stimulation. Our results suggest that REMs during sleep rearrange discrete epochs of visual-like processing as during wakefulness. PMID- 26262926 TI - What memory is. AB - I argue that our current practice of ascribing the term 'memory' to mental states and processes lacks epistemic warrant. Memory, according to the 'received view', is any state or process that results from the sequential stages of encoding, storage, and retrieval. By these criteria, memory, or its footprint, can be seen in virtually every mental state we are capable of having. This, I argue, stretches the term to the breaking point. I draw on phenomenological, historical, and conceptual considerations to make the case that an act of memory entails a direct, non-inferential feeling of reacquaintance with one's past. It does so by linking content retrieved from storage with autonoetic awareness during retrieval. On this view, memory is not the content of experience, but the manner in which that content is experienced. I discuss some theoretical and practical implications and advantages of adopting this more circumscribed view of memory. PMID- 26262925 TI - Partial Unwrapping and Histone Tail Dynamics in Nucleosome Revealed by Coarse Grained Molecular Simulations. AB - Nucleosomes, basic units of chromatin, are known to show spontaneous DNA unwrapping dynamics that are crucial for transcriptional activation, but its structural details are yet to be elucidated. Here, employing a coarse-grained molecular model that captures residue-level structural details up to histone tails, we simulated equilibrium fluctuations and forced unwrapping of single nucleosomes at various conditions. The equilibrium simulations showed spontaneous unwrapping from outer DNA and subsequent rewrapping dynamics, which are in good agreement with experiments. We found several distinct partially unwrapped states of nucleosomes, as well as reversible transitions among these states. At a low salt concentration, histone tails tend to sit in the concave cleft between the histone octamer and DNA, tightening the nucleosome. At a higher salt concentration, the tails tend to bound to the outer side of DNA or be expanded outwards, which led to higher degree of unwrapping. Of the four types of histone tails, H3 and H2B tail dynamics are markedly correlated with partial unwrapping of DNA, and, moreover, their contributions were distinct. Acetylation in histone tails was simply mimicked by changing their charges, which enhanced the unwrapping, especially markedly for H3 and H2B tails. PMID- 26262927 TI - Attention-deficit hyperactivity disorder, multimodal treatment, and longitudinal outcome: evidence, paradox, and challenge. AB - Given major increases in the diagnosis of attention-deficit hyperactivity disorder (ADHD) and in rates of medication for this condition, we carefully examine evidence for effects of single versus multimodal (i.e., combined medication and psychosocial/behavioral) interventions for ADHD. Our primary data source is the Multimodal Treatment Study of Children with ADHD (MTA), a 14-month, randomized clinical trial in which intensive behavioral, medication, and multimodal treatment arms were contrasted with one another and with community intervention (treatment-as-usual), regarding outcome domains of ADHD symptoms, comorbidities, and core functional impairments. Although initial reports emphasized the superiority of well-monitored medication for symptomatic improvement, reanalyses and reappraisals have highlighted (1) the superiority of combination treatment for composite outcomes and for domains of functional impairment (e.g., academic achievement, social skills, parenting practices); (2) the importance of considering moderator and mediator processes underlying differential patterns of outcome, including comorbid subgroups and improvements in family discipline style during the intervention period; (3) the emergence of side effects (e.g., mild growth suppression) in youth treated with long-term medication; and (4) the diminution of medication's initial superiority once the randomly assigned treatment phase turned into naturalistic follow-up. The key paradox is that while ADHD clearly responds to medication and behavioral treatment in the short term, evidence for long-term effectiveness remains elusive. We close with discussion of future directions and a call for greater understanding of relevant developmental processes in the attempt to promote optimal, generalized, and lasting treatments for this important and impairing neurodevelopmental disorder. PMID- 26262928 TI - Changing brains: how longitudinal functional magnetic resonance imaging studies can inform us about cognitive and social-affective growth trajectories. AB - Brain imaging studies have demonstrated widespread changes in brain networks which support cognitive and social-affective development. These conclusions, however, are largely based on cross-sectional comparisons, which limits the possibility to investigate growth trajectories and detect individual changes. Understanding individual growth patterns is crucial if we want to ultimately understand how brain development is sensitive to environmental influences such as educational or psychological interventions or childhood maltreatment. Recently, longitudinal brain imaging studies in children and adolescents have taken the first steps into examining cognitive and social-affective brain functions longitudinally with several compelling findings. First, longitudinal measurements show that activations in some brain regions, such as the prefrontal, temporal, and parietal cortex, are relatively stable over time and can be used as predictors for cognitive functions, whereas activations in other brain regions, such as the amygdala and ventral striatum, are much more variable over time. Second, developmental studies reveal how these changes are related to age, puberty, and changes in performance. These findings have implications for understanding how environmental factors influence brain development. An important future direction will be to examine individual characteristics (e.g., genetic, temperamental, personality) which make individuals differentially susceptible to their environment. PMID- 26262929 TI - Computational modeling of the mind: what role for mental representation? AB - The classical computational theory of mind (CTM) holds that many important mental processes are computations similar to those executed by Turing machines. This article compares two alternative frameworks through which one can develop CTM: formal-syntactic computationalism and content-involving computationalism. According to formal-syntactic computationalism, computation is sensitive to syntax but not semantics. Mental computation manipulates formal-syntactic items without regard to any representational properties those items may have. According to content-involving computationalism, certain computational descriptions characterize mental states through their representational properties rather than any alleged formal-syntactic properties. The article examines strengths and weaknesses of each framework. PMID- 26262931 TI - Vagus nerve stimulation in neuropsychiatry: Targeting anatomy-based stimulation sites. AB - The vagus nerve (VN) is the longest cranial nerve, extending from the brain to the abdominal cavity. The VN consists of both afferent and efferent fibers (respectively 80% and 20%). Vagus nerve stimulation (VNS) is a neuromodulation strategy first developed in the 1980s for epilepsy. More recently, growing efforts in clinical research have been underscoring possible clinical benefits of VNS for different medical conditions such as epilepsy, major depression, anxiety disorders, and Tourette syndrome. Following the rational of VN anatomy and cranial innervation presented above, we hereby hypothesize that transcutaneously placing electrodes over the mastoid process could be a useful study protocol for future tVNS trials. PMID- 26262932 TI - CHD2 mutations are a rare cause of generalized epilepsy with myoclonic-atonic seizures. AB - Chromodomain helicase DNA-binding protein 2 (CHD2) gene mutations have been reported in patients with myoclonic-atonic epilepsy (MAE), as well as in patients with Lennox-Gastaut, Dravet, and Jeavons syndromes and other epileptic encephalopathies featuring generalized epilepsy and intellectual disability. The aim of this study was to assess the impact of CHD2 mutations in a series of patients with MAE. Twenty patients affected by MAE were included in the study. We analyzed antecedents, age at onset, seizure semiology and frequency, EEG, treatment, and neuropsychological outcome. We sequenced the CHD2 gene with Sanger technology. We identified a CHD2 frameshift mutation in one patient (c.4256del19). He was a 17-year-old boy with no familial history for epilepsy and normal development before epilepsy onset. Epilepsy onset was at 3years and 5months: he presented with myoclonic-atonic seizures, head drops, myoclonic jerks, and absences. Interictal EEGs revealed slow background activity associated with generalized epileptiform abnormalities and photoparoxysmal response. His seizures were highly responsive to valproic acid, and an attempt to withdraw it led to seizure recurrence. Neuropsychological evaluation revealed moderate intellectual disability. Chromodomain-helicase-DNA-binding protein 2 is not the major gene associated with MAE. Conversely, CHD2 could be responsible for a proper phenotype characterized by infantile-onset generalized epilepsy, intellectual disability, and photosensitivity, which might overlap with MAE, Lennox-Gastaut, Dravet, and Jeavons syndromes. PMID- 26262933 TI - Unplanned hospital use by people with epilepsy: A lever by which to bring about increased self-management support? PMID- 26262934 TI - Delusional experience awareness gap between patients and treating doctors - Self reported EPDS questionnaire. AB - OBJECTIVES: Although early and rapid recognition of a psychotic trend in patients with epilepsy certainly pay dividends, there is no handy assessment instrument for screening because of multiple intrinsic difficulties such as lack of a standard screener as well as a reliability gap for screeners between help-seeking and general populations. On the other hand, the predominance of positive symptoms at the initial stage of psychosis is a promising aspect of this specific group. The following specific questions were examined. Is there a measurable difference between the assessment of the treating doctor and the real feelings of the patient? How well does the attained score correspond to the clinical diagnosis? METHODS: The self-reported Emotions with Persecutory Delusions Scale (EPDS) questionnaire, previously validated in a general population, was used as the assessment tool for psychotic trend in 79 outpatients with epilepsy. Independent from scoring by the patients, the treating doctors also expressed their impressions about the same patients using the same scoring tool. RESULTS: Stepwise multiple regression analysis of the EPDS scores of both doctors and patients revealed that a clinical diagnosis of psychosis was the only independent variable significantly related to EPDS score. Also, there was a significant difference between the EPDS scores of the patients and those of the doctors, in favor of the former. SIGNIFICANCE: Clinical diagnosis of psychosis proved to be the most powerful determinant of EPDS score independent from other clinical factors. The awareness gap between doctors and patients based on EPDS score revealed that treating doctors often clearly underestimate the psychotic trend of their patients. Our findings suggest that such simple tests as EPDS, with a narrow focus on attenuated delusional symptoms, may help screen for an early psychotic episode in patients with epilepsy that may otherwise not be diagnosed by their physicians. PMID- 26262935 TI - Development and validation of an epidemiologic case definition of epilepsy for use with routinely collected Australian health data. AB - OBJECTIVES: We report the diagnostic validity of a selection algorithm for identifying epilepsy cases. STUDY DESIGN AND SETTING: Retrospective validation study of International Classification of Diseases 10th Revision Australian Modification (ICD-10AM)-coded hospital records and pharmaceutical data sampled from 300 consecutive potential epilepsy-coded cases and 300 randomly chosen cases without epilepsy from 3/7/2012 to 10/7/2013. Two epilepsy specialists independently validated the diagnosis of epilepsy. A multivariable logistic regression model was fitted to identify the optimum coding algorithm for epilepsy and was internally validated. RESULTS: One hundred fifty-eight out of three hundred (52.6%) epilepsy-coded records and 0/300 (0%) nonepilepsy records were confirmed to have epilepsy. The kappa for interrater agreement was 0.89 (95% CI=0.81-0.97). The model utilizing epilepsy (G40), status epilepticus (G41) and >=1 antiepileptic drug (AED) conferred the highest positive predictive value of 81.4% (95% CI=73.1-87.9) and a specificity of 99.9% (95% CI=99.9-100.0). The area under the receiver operating curve was 0.90 (95% CI=0.88-0.93). CONCLUSION: When combined with pharmaceutical data, the precision of case identification for epilepsy data linkage design was considerably improved and could provide considerable potential for efficient and reasonably accurate case ascertainment in epidemiological studies. PMID- 26262936 TI - To tell or not to tell: A systematic review of the disclosure practices of children living with epilepsy and their parents. AB - Disclosing an epilepsy diagnosis to others is complex due to the condition's largely invisible nature and associated stigma. Despite this, little has been documented in terms of what this process involves for children living with epilepsy (CWE) and their parents. A systematic review was conducted to examine and synthesize evidence pertaining to: (i) the disclosure practices of CWE and their parents, (ii) enablers and barriers for disclosure, (iii) the impact of disclosure practices, and (iv) the relationship between disclosure management and other variables. The electronic databases PsycINFO, PubMed, MEDLINE, CINAHL, Scopus, and Web of Science were searched systematically. Any empirical, peer reviewed journal articles with findings reported regarding the self- or proxy reported disclosure practices of children aged 0-18years with any type of epilepsy and/or their parents were deemed eligible for inclusion. Two review authors completed all stages of screening, data extraction, and quality assessment independently with two additional review authors resolving any discrepancies. A total of 32 articles were included in the review. Only one dated study examined disclosure as a primary focus; in the remaining studies, disclosure was a subfocus of larger studies or pertinent qualitative themes/subthemes incidentally emerged. The limited evidence suggests that: 1) CWE and parents adopt varying disclosure management strategies - from concealment to voluntary disclosure; 2) disclosure decisions are challenging for CWE and parents; 3) many barriers to disclosure exist (e.g., fear of stigmatization and rejection); 4) only a limited number of factors that enable disclosure are known (e.g., openness by others to engage with and learn about epilepsy); 5) disclosure management is significantly related to a number of variables (e.g., child/maternal perceived stigma and seizure control); and 6) there are varying outcomes for CWE and/or their parents in accordance with the adoption of specific disclosure management strategies (e.g., disclosure resulting in greater acceptance and the receipt of support or evoking anxiety/fear in others; and concealment resulting in misunderstandings, embarrassment, and stigma-coaching), but the evidence remains inconclusive in terms of which disclosure management strategy is optimal. While some preliminary work has been conducted, disclosure of epilepsy is a topic that has been largely neglected to date. This is despite the fact that disclosure is a significant source of concern for CWE and parent populations. Future studies should focus on elucidating the unique contextual factors that inform disclosure decisions in order to develop a theoretical framework that can explain the epilepsy disclosure decision-making process. PMID- 26262938 TI - Disruption of learning and long-term retention of prose passages in patients with focal epilepsy. AB - Recent investigations of accelerated long-term forgetting, a condition in which newly acquired memory is normal initially but decays rapidly over days or weeks, indicate that multiple factors might influence whether this phenomenon is seen in patients with epilepsy. Test-based differences such as learning condition or type of memory measure (e.g., recall vs recognition) as well as epilepsy variables (e.g., side, site, or frequency of epileptiform activity) may be important. The present study sought to characterize factors affecting learning and memory for prose passages in patients with focal epilepsy. We enrolled 21 patients with temporal lobe epilepsy, with and without hippocampal lesions, 11 patients with extratemporal epilepsy (ETE), and 29 healthy controls. Two matched passages were used to compare effects of initial learning condition (one exposure versus learning-to-criterion) on subsequent patterns of retention. Recall and recognition were tested at different delays (i.e., immediately, 30min, 24h, and 4days). Regression analyses and one-way ANOVAs indicated that having a left hemisphere epileptic focus had a negative impact on learning, whilst presence of a hippocampal lesion (irrespective of side) was associated with deterioration in recall for intervals up to 24h postencoding. Learning condition affected patterns of memory decay in that the ETE group showed significant decline in recall between 24h and 4days only when stories were learned to criterion. In contrast with recall, no changes over time were evident in recognition memory, as patients with hippocampal lesions were impaired from 30min onward. Epilepsy variables other than side and site of epilepsy/lesion did not influence performance. In conclusion, the left hemisphere is involved in learning of prose material, and the hippocampus is involved in the consolidation of this material mainly for the first 24h. After this, cortical regions outside the hippocampus become important for recall. PMID- 26262937 TI - Inhibition of glutamine synthetase in the central nucleus of the amygdala induces anhedonic behavior and recurrent seizures in a rat model of mesial temporal lobe epilepsy. AB - The prevalence of depression and suicide is increased in patients with mesial temporal lobe epilepsy (MTLE); however, the underlying mechanism remains unknown. Anhedonia, a core symptom of depression that is predictive of suicide, is common in patients with MTLE. Glutamine synthetase, an astrocytic enzyme that metabolizes glutamate and ammonia to glutamine, is reduced in the amygdala in patients with epilepsy and depression and in suicide victims. Here, we sought to develop a novel model of anhedonia in MTLE by testing the hypothesis that deficiency in glutamine synthetase in the central nucleus of the amygdala (CeA) leads to epilepsy and comorbid anhedonia. Nineteen male Sprague-Dawley rats were implanted with an osmotic pump infusing either the glutamine synthetase inhibitor methionine sulfoximine [MSO (n=12)] or phosphate buffered saline [PBS (n=7)] into the right CeA. Seizure activity was monitored by video-intracranial electroencephalogram (EEG) recordings for 21days after the onset of MSO infusion. Sucrose preference, a measure of anhedonia, was assessed after 21days. Methionine sulfoximine-infused rats exhibited recurrent seizures during the monitoring period and showed decreased sucrose preference over days when compared with PBS infused rats (p<0.01). Water consumption did not differ between the PBS-treated group and the MSO-treated group. Neurons were lost in the CeA, but not the medial amygdala, lateral amygdala, basolateral amygdala, or the hilus of the dentate gyrus, in the MSO-treated rats. The results suggest that decreased glutamine synthetase activity in the CeA is a possible common cause of anhedonia and seizures in TLE. We propose that the MSO CeA model can be used for mechanistic studies that will lead to the development and testing of novel drugs to prevent seizures, depression, and suicide in patients with TLE. PMID- 26262939 TI - Psychometric validation of the Pediatric Symptom Checklist-17 in a pediatric population with epilepsy: A methods study. AB - OBJECTIVE: The purpose of this study was to address critical gaps in behavioral health care of youth with epilepsy by examining the utility of a brief, well validated screening instrument, the PSC-17, in a pediatric population with epilepsy. METHOD: One hundred eighty-seven caregivers of youth with epilepsy ages 2-17years completed the PSC-17 for their child/adolescent during a routine epilepsy visit. Demographic and seizure information was abstracted from electronic medical record review. RESULTS: Confirmatory factor analyses for the PSC-17 revealed an acceptable fit with the 3-factor model, chi(2) (116 [N=187]=204.54, p<0.001, CFI=0.90, TLI=0.88, RMSEA=0.064, SRMSR=0.078). Scale level reliabilities were excellent (0.72-0.85). Interscale correlations were moderate (0.48-0.69). Approximately 1/5th of the sample met clinical cut-offs for the total score of behavioral health concerns. However, an additional 20% of the sample had at least one elevated subscale score despite the total score being in the normative/nonclinical range. SIGNIFICANCE: The PSC-17 is a brief, free behavioral health screening tool with adequate to strong validity, reliability, and clinical utility for pediatric populations with epilepsy. Clinicians should consider using the 3 PSC-17 subscale scores instead of the total score to guide referrals for further evaluation as the subscales may provide a more accurate picture of functioning in particular domains. PMID- 26262940 TI - Cognition and behavior in a prevalent cohort of children with epilepsy in rural northern Tanzania: A three-year follow-up study. AB - OBJECTIVES: Eighty-five percent of the 33 million children with epilepsy (CWE) worldwide live in low- and middle-income countries (LMICs). There is limited research into epilepsy-related comorbidities in LMICs, and there are no studies of the long-term progression of behavioral and intellectual difficulties in childhood epilepsy in sub-Saharan Africa. We aimed to assess behavior and cognition at three-year follow-up in CWE in rural Tanzania. METHODS: In 2010, a cross-sectional study identified 112 CWE 6 to 14years of age and 113 age- and sex matched controls in the Hai district of northern Tanzania. From March to June 2013, cases and controls (now 10 to 18years of age) were followed up. At baseline, behavior was assessed using the Rutter A Questionnaire and cognition using the Goodenough-Harris Drawing Test. Details of current seizure frequency and antiepileptic drug (AED) use among CWE were collected. RESULTS: At follow-up, cases had significantly more behavioral difficulties compared with controls (48% of 108 cases versus 14% of 103 controls (p<0.001)). Additionally, 69% of the cases and 16% of the controls had cognitive impairment (p<0.001). In CWE with decreased seizure frequency from baseline to follow-up, behavior had improved significantly. At follow-up, there was no significant difference in behavior between CWE with decreased seizure frequency and those with good seizure control throughout. SIGNIFICANCE: Behavioral difficulties and cognitive impairment are common among CWE in this population. Improved access to AED treatment and subsequent improved seizure control may reduce the frequency of behavioral difficulties seen in this population. PMID- 26262942 TI - Advanced Cancer and End-of-Life Preferences: Curative Intent Surgery Versus Noncurative Intent Treatment. AB - BACKGROUND: People with cancer face complex medical decisions, including whether to receive life-sustaining treatments at the end of life. It is not unusual for clinicians to make assumptions about patients' wishes based on whether they had previously chosen to pursue curative treatment. OBJECTIVE: We hypothesized that cancer patients who initially underwent curative intent surgery (CIS) would prefer more aggressive end-of-life treatments compared to patients whose treatment was noncurative intent (non-CIT). METHODS: This study was a retrospective review of data from a large, randomized controlled trial examining the use of an online decision aid for advance care planning, "Making Your Wishes Known" (MYWK), with patients who had advanced cancer. We reviewed patients' medical records to determine which patients underwent CIS versus non-CIT. In the parent trial, conducted at an academic medical center (2007-2012), 200 patients were enrolled with stage IV malignancy or other poor prognosis cancer. Patients' preferences for aggressive treatment were measured in two ways: using patient selected General Wishes statements generated by the decision aid and patient selected wishes for specific treatments under various hypothetical clinical scenarios (Specific Wishes). RESULTS: We evaluated 79 patients. Of these, 48 had undergone initial CIS and 31 had non-CIT. Cancer patients who initially underwent CIS did not prefer more aggressive end-of-life treatments compared to patients whose treatment was non-CIT. CONCLUSIONS: Clinicians should avoid assumptions about patients' preferences for life-sustaining treatment based on their prior choices for aggressive treatment. PMID- 26262943 TI - Structure-Property Correlations in Cyanobiphenyl-Based Dimer-Like Mesogens. AB - In this contribution, we present the results of our extensive investigations on the synthesis and phase behavior of five series of dimer-like compounds formed by covalently linking a promesogenic, cyanobiphenyl core, with a nonmesogenic N-(n alkyl)-salicylaldimine segment via an oxy(oligomethylene)oxy spacer of varying length and parity. This work is a continuation of our previous short study where the occurrence of re-entrant nematic (Nre) phase seemed to be vitally dependent on the parity of the spacer and the length of the terminal chain. Thus, working along these lines the effects on the thermal (Nre phase) behavior of the various spacers and the terminal tails have been investigated comprehensively. In particular, with the aim of exploring the fundamental relationships between molecular structural features and thermal properties, five spacers, namely, oxy(hexyl)oxy, oxy(heptyl)oxy, oxy(octyl)oxy, oxy(nonyl)oxy, and oxy(decyl)oxy spacers, have been used. Each series consists of six mesogens, as the terminal tail attached to the salicylaldimine core has been varied from n-pentyl to n decyl. For the sake of comparison and completeness, previously reported materials have also been studied in detail, and data are included here. The characterization results derived from the optical and calorimetric studies clearly illustrate a pronounced odd-even effect; however, the effect attenuates as the length of the spacer is elongated. The even-members show higher clearing temperatures and enthalpies of transition than those of adjoining odd-members. Three series of mesogens possessing an even-parity spacer show thermodynamically stable nematic (N) and/or smectic A (SmA) phase(s); the lower homologues display only the N phase, and the middle ones exhibit both N and SmA phases while the higher members show the SmA phase solely. In contrast, the vast majority of the odd-spaced compounds of two series show a monotropic N phase. X-ray diffraction study confirms the partial bilayer order of the SmA (SmAd) phase with L < d < 2L where d is the layer spacing and L is the molecular length. Contrary to what was previously noted, none of the new compounds synthesized favor the stabilization of the Nre phase. At the present time, it is extremely difficult to point out the exact cause for the origin of re-entrant behavior in some compounds exclusively, as they hardly differ in their structure. It was also found that the phase transitional properties of even-members are comparable to that observed for 4'-n alkoxy-4-cyanobiphenyls (nOCBs) and 4-n-alkyl-4-cyanobiphenyls (nCBs). In essence, our study validates the point that dimer-like compounds resemble liquid crystal (LC) dimers, as well as monomers to some degree, in the context of their thermal behavior; thus, they can be regarded as the bridging structures between LC monomers and dimers. PMID- 26262941 TI - Designing Caregiver-Implemented Shared-Reading Interventions to Overcome Implementation Barriers. AB - PURPOSE: This study presents an application of the theoretical domains framework (TDF; Michie et al., 2005), an integrative framework drawing on behavior-change theories, to speech-language pathology. METHODS: A multistep procedure was used to identify barriers affecting caregivers' implementation of shared-reading interventions with their children with language impairment (LI). The authors examined caregiver-level data corresponding to implementation issues from two randomized controlled trials and mapped these to domains in the TDF as well as empirically validated behavior-change techniques. RESULTS: Four barriers to implementation were identified as potentially affecting caregivers' implementation: time pressures, reading difficulties, discomfort with reading, and lack of awareness of benefits. These were mapped to 3 TDF domains: intentions, beliefs about capabilities, and skills. In turn, 4 behavior-change techniques were identified as potential vehicles for affecting these domains: reward, feedback, model, and encourage. An ongoing study is described that is determining the effects of these techniques for improving caregivers' implementation of a shared-reading intervention. CONCLUSIONS: A description of the steps to identifying barriers to implementation, in conjunction with an ongoing experiment that will explicitly determine whether behavior-change techniques affect these barriers, provides a model for how implementation science can be used to identify and overcome implementation barriers in the treatment of communication disorders. PMID- 26262944 TI - Preparation of Fluorinated Tetrahydropyrans and Piperidines using a New Nucleophilic Fluorination Reagent DMPU/HF. AB - DMPU/HF (HF content 65 wt %/wt) is an ideal nucleophilic fluorination reagent for the diastereoselective synthesis of substituted 4-fluorotetrahydropyrans and 4 fluoropiperidines via a fluoro-Prins reaction. When compared to classical nucleophilic fluorination reagents like pyridine/HF, DMPU/HF gives both higher yields and better diastereoselectivity. PMID- 26262945 TI - An Exploration of Parenting Stress in Immigrant and Taiwanese Mothers. AB - To assess parenting stress and major difficulties experienced in early motherhood among immigrant and Taiwanese women in Pingtung, southern Taiwan. A comparative, descriptive, cohort study of parenting stress and maternal psychological health, using the Child Care Stress Checklist and Edinburgh Postpartum Depression Scale. A purposive sample of 26 foreign-born Vietnamese and 162 Taiwanese mothers were surveyed at 6 weeks' postpartum. Both groups of mothers experienced similar parenting difficulties including the establishment of a regular sleeping schedule for the infant, consoling a crying infant, awareness of infant's needs, conflict with family members, and difficulties managing household chores. Curtailment of social activities was reported more often by Taiwanese mothers, whereas inaccessibility to other experienced mothers and poor maternal-infant bonding were experienced more by immigrant mothers. There were significant differences between groups, with high levels of child care stress and postpartum depression symptoms reported more often by immigrant mothers. Nurses-midwives and community child health nurses need to be sensitive to the particular difficulties and stresses of parenting in mothers from different backgrounds and provide effective interventions and support activities. PMID- 26262946 TI - Carbon Dioxide Laser Correction of an Occult Camouflage Tattoo Unintentionally Darkened by Q-Switched Laser Exposure. PMID- 26262947 TI - Perineural Invasion in Atypical Fibroxanthoma of the Scalp and Forehead. PMID- 26262948 TI - Healing of Recalcitrant Chronic Venous Leg Ulcers by Punch Grafts Harvested From the Scalp. PMID- 26262949 TI - Arterial Catheter Use in the ICU: A National Survey of Antiseptic Technique and Perceived Infectious Risk. AB - OBJECTIVES: Recent studies have shown that the occurrence rate of bloodstream infections associated with arterial catheters is 0.9-3.4/1,000 catheter-days, which is comparable to that of central venous catheters. In 2011, the Centers for Disease Control and Prevention published new guidelines recommending the use of limited barrier precautions during arterial catheter insertion, consisting of sterile gloves, a surgical cap, a surgical mask, and a small sterile drape. The goal of this study was to assess the attitudes and current infection prevention practices used by clinicians during insertion of arterial catheters in ICUs in the United States. DESIGN: An anonymous, 22-question web-based survey of infection prevention practices during arterial catheter insertion. SETTING: Clinician members of the Society of Critical Care Medicine. SUBJECTS: Eleven thousand three hundred sixty-one physicians, nurse practitioners, physician assistants, respiratory therapists, and registered nurses who elect to receive e mails from the Society of Critical Care Medicine. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 1,265 responses (11% response rate), with 1,029 eligible participants after exclusions were applied. Only 44% of participants reported using the Centers for Disease Control and Prevention recommended barrier precautions during arterial catheter insertion, and only 15% reported using full barrier precautions. The mean and median estimates of the incidence density of bloodstream infections associated with arterial catheters were 0.3/1,000 catheter-days and 0.1/1,000 catheter-days, respectively. Thirty nine percent of participants reported that they would support mandatory use of full barrier precautions during arterial catheter insertion. CONCLUSIONS: Barrier precautions are used inconsistently by critical care clinicians during arterial catheter insertion in the ICU setting. Less than half of clinicians surveyed were in compliance with current Centers for Disease Control and Prevention guidelines. Clinicians significantly underestimated the infectious risk posed by arterial catheters, and support for mandatory use of full barrier precautions was low. Further studies are warranted to determine the optimal preventive strategies for reducing bloodstream infections associated with arterial catheters. PMID- 26262950 TI - Critical Care Organizations in Academic Medical Centers in North America: A Descriptive Report. AB - OBJECTIVES: With the exception of a few single-center descriptive reports, data on critical care organizations are relatively sparse. The objectives of our study were to determine the structure, governance, and experience to date of established critical care organizations in North American academic medical centers. DESIGN: A 46-item survey questionnaire was electronically distributed using Survey Monkey to the leadership of 27 identified critical care organizations in the United States and Canada between September 2014 and February 2015. A critical care organization had to be headed by a physician and have primary governance over the majority, if not all, of the ICUs in the medical center. MEASUREMENTS AND MAIN RESULTS: We received 24 responses (89%). The majority of the critical care organizations (83%) were called departments, centers, systems, or operations committees. Approximately two thirds of respondents were from larger (> 500 beds) urban institutions, and nearly 80% were primary university medical centers. On average, there were six ICUs per academic medical center with a mean of four ICUs under critical care organization governance. In these ICUs, intensivists were present in-house 24/7 in 49%; advanced practice providers in 63%; hospitalists in 21%; and telemedicine coverage in 14%. Nearly 60% of respondents indicated that they had a separate hospital budget to support data management and reporting, oversight of their ICUs, and rapid response teams. The transition from the traditional model of ICUs within departmentally controlled services or divisions to a critical care organization was described as gradual in 50% and complete in only 25%. Nearly 90% indicated that their critical care organization governance structure was either moderately or highly effective; a similar number suggested that their critical care organizations were evolving with increasing domain and financial control of the ICUs at their respective institutions. CONCLUSIONS: Our survey of the very few critical care organizations in North American academic medical centers showed that the governance models of critical care organizations vary and continue to evolve. Additional studies are warranted to improve our understanding of the factors that can foster the growth of critical care organizations and how they can be effective. PMID- 26262951 TI - Cell Membrane Capsules for Encapsulation of Chemotherapeutic and Cancer Cell Targeting in Vivo. AB - Systemic administration of chemotherapeutic agents can cause indiscriminate drug distribution and severe toxicity. Until now, encapsulation and targeting of drugs have typically relied on synthetic vehicles, which cannot minimize the clearance by the renal system and may also increase the risk of chemical side effects. Cell membrane capsules (CMCs) provide a generic and far more natural approach to the challenges of drug encapsulation and delivery in vivo. Here aptamer AS1411, which can recognize and bind overexpressed nucleolin on a cancer cell membrane, was chemically conjugated onto CMCs. As a result, AS1411 modified CMCs showed enhanced ingestion in certain cancer cells in vitro and accumulation in mouse cancer xenografts in vivo. Chemotherapeutics and contrast agents with therapeutically significant concentrations can be packaged into CMCs by reversible permeating their plasma membranes. The systematic administration of cancer targeting CMCs loaded with doxorubicin hydrochloride can significantly inhibit tumor growth in mouse xenografts, with significantly reduced toxicity compared to free drug. These findings suggest that cancer targeting CMCs may have considerable benefits in drug delivery and cancer treatment. PMID- 26262955 TI - Clustangles: An Open Library for Clustering Angular Data. AB - Dihedral angles are good descriptors of the numerous conformations visited by large, flexible systems, but their analysis requires directional statistics. A single package including the various multivariate statistical methods for angular data that accounts for the distinct topology of such data does not exist. Here, we present a lightweight standalone, operating-system independent package called Clustangles to fill this gap. Clustangles will be useful in analyzing the ever increasing number of structures in the Protein Data Bank and clustering the copious conformations from increasingly long molecular dynamics simulations. PMID- 26262957 TI - Dissociative Electron Attachment to Resveratrol as a Likely Pathway for Generation of the H2 Antioxidant Species Inside Mitochondria. AB - The electron-attaching properties of polyphenolic compound resveratrol were studied in vacuo by means of dissociative electron attachment (DEA) spectroscopy and in silico using density functional theory calculations. The most intense fragments generated by DEA to isolated resveratrol at thermal electron energy are semiquinone anions and neutral hydrogen molecules. On the basis of the present experimental and theoretical data, a new molecular mechanism for the antioxidant activity of resveratrol is presented. It is suggested that the activity of resveratrol in living cells is driven by dissociative attachment of electrons "leaked" from the respiratory chain to this polyphenolic molecule, followed by the formation of the H2 antioxidant species inside mitochondria and participation in mitochondrial energy biogenesis. PMID- 26262958 TI - What Is the Structure of the Naphthalene-Benzene Heterodimer Radical Cation? Binding Energy, Charge Delocalization, and Unexpected Charge-Transfer Interaction in Stacked Dimer and Trimer Radical Cations. AB - The binding energy of the naphthalene(+*)(benzene) heterodimer cation has been determined to be 7.9 +/- 1 kcal/mol for C10H8(+*)(C6H6) and 8.1 +/- 1 kcal/mol for C10H8(+*)(C6D6) by equilibrium thermochemical measurements using the mass selected drift cell technique. A second benzene molecule binds to the C10H8(+*)(C6D6) dimer with essentially the same energy (8.4 +/- 1 kcal/mol), suggesting that the two benzene molecules are stacked on opposite sides of the naphthalene cation in the (C6D6)C10H8(+*)(C6D6) heterotrimer. The lowest-energy isomers of the C10H8(+*)(C6D6) and (C6D6)C10H8(+*)(C6D6) dimer and trimer calculated using the M11/cc-pVTZ method have parallel stacked structures with enthalpies of binding (-DeltaH degrees ) of 8.4 and 9.0 kcal/mol, respectively, in excellent agreement with the experimental values. The stacked face-to-face class of isomers is calculated to have substantial charge-transfer stabilization of about 45% of the total interaction energy despite the large difference between the ionization energies of benzene and naphthalene. Similarly, significant delocalization of the positive charge is found among all three fragments of the (C6D6)C10H8(+*)(C6D6) heterotrimer, thus leaving only 46% of the total charge on the central naphthalene moiety. This unexpectedly high charge-transfer component results in activating two benzene molecules in the naphthalene(+*)(benzene)2 heterotrimer cation to associate with a third benzene molecule at 219 K to form a benzene trimer cation and a neutral naphthalene molecule. The global minimum of the C10H8(+*)(C6H6)2 heterotrimer is found to be the one where the naphthalene cation is sandwiched between two benzene molecules. It is remarkable, and rather unusual, that the binding energy of the second benzene molecule is essentially the same as that of the first. This is attributed to the enhanced charge-transfer interaction in the stacked trimer radical cation. PMID- 26262959 TI - Superhalogens: A Bridge between Complex Metal Hydrides and Li Ion Batteries. AB - Complex metal hydrides and Li ion batteries play an integral role in the pursuit of clean and sustainable energy. The former stores hydrogen and can provide a clean energy solution for the transportation industry, while the latter can store energy harnessed from the sun and the wind. However, considerable materials challenges remain in both cases, and research for finding solutions has traditionally followed parallel paths. In this Perspective, I show that there is a common link between these two seemingly disparate fields that can be unveiled by studying the electronic structure of the anions in complex metal hydrides and in electrolytes of Li ion batteries; they are both superhalogens. I demonstrate that considerable progress made in our understanding of superhalogens in the past decade can provide solutions to some of the materials challenges in both of these areas. PMID- 26262956 TI - Validation of Next-Generation Sequencing of Entire Mitochondrial Genomes and the Diversity of Mitochondrial DNA Mutations in Oral Squamous Cell Carcinoma. AB - BACKGROUND: Oral squamous cell carcinoma (OSCC) is mainly caused by smoking and alcohol abuse and shows a five-year survival rate of ~50%. We aimed to explore the variation of somatic mitochondrial DNA (mtDNA) mutations in primary oral tumors, recurrences and metastases. METHODS: We performed an in-depth validation of mtDNA next-generation sequencing (NGS) on an Illumina HiSeq 2500 platform for its application to cancer tissues, with the goal to detect low-level heteroplasmies and to avoid artifacts. Therefore we genotyped the mitochondrial genome (16.6 kb) from 85 tissue samples (tumors, recurrences, resection edges, metastases and blood) collected from 28 prospectively recruited OSCC patients applying both Sanger sequencing and high-coverage NGS (~35,000 reads per base). RESULTS: We observed a strong correlation between Sanger sequencing and NGS in estimating the mixture ratio of heteroplasmies (r = 0.99; p<0.001). Non synonymous heteroplasmic variants were enriched among cancerous tissues. The proportions of somatic and inherited variants in a given gene region were strongly correlated (r = 0.85; p<0.001). Half of the patients shared mutations between benign and cancerous tissue samples. Low level heteroplasmies (<10%) were more frequent in benign samples compared to tumor samples, where heteroplasmies >10% were predominant. Four out of six patients who developed a local tumor recurrence showed mutations in the recurrence that had also been observed in the primary tumor. Three out of five patients, who had tumor metastases in the lymph nodes of their necks, shared mtDNA mutations between primary tumors and lymph node metastases. The percentage of mutation heteroplasmy increased from the primary tumor to lymph node metastases. CONCLUSIONS: We conclude that Sanger sequencing is valid for heteroplasmy quantification for heteroplasmies >=10% and that NGS is capable of reliably detecting and quantifying heteroplasmies down to the 1%-level. The finding of shared mutations between primary tumors, recurrences and metastasis indicates a clonal origin of malignant cells in oral cancer. PMID- 26262960 TI - IR Near-Field Study of the Solid Electrolyte Interphase on a Tin Electrode. AB - There has been a dearth of suitable techniques for studying the chemical composition of solid electrolyte interphase (SEI) on Li-ion negative electrodes at a resolution of its basic building blocks' length scale. Infrared apertureless near-field scanning optical microscopy (IR aNSOM) is an emerging tool in the chemical characterization of interfacial layers on the nanometer scale. This work demonstrates an IR aNSOM imaging of the SEI layer on a model Sn electrode. IR aNSOM images reveal significant chemical contrast variations tied to specific topographic features and possible corresponding distribution of lithium carbonate and lithium ethylene dicarbonate on the Sn electrode surface. PMID- 26262961 TI - Identical Hydrogen-Bonding Strength of the Retinal Schiff Base between Primate Green- and Red-Sensitive Pigments: New Insight into Color Tuning Mechanism. AB - Three aspects are generally considered in the color-tuning mechanism of vision: (I) chromophore distortion, (II) electrostatic interaction between the protonated Schiff base and counterion, and (III) polarity around the beta-ionone ring and polyene chain. Primate green- and red-sensitive proteins are highly homologous but display maximum absorption at 530 and 560 nm, respectively. In the present study, the N-D stretching frequency of monkey green-sensitive protein was identified by using C15-D retinal. The hydrogen-bonding strength between monkey green and red was identical. Together with a previous resonance Raman study, we conclude that the 30 nm difference originates exclusively from the polarity around the beta-ionone ring and polyene chain. Three amino acids (Ala, Phe, and Ala in monkey green and Ser, Tyr, and Thr in monkey red, respectively) may be responsible for color tuning together with protein-bound water molecules around the beta-ionone ring and polyene chain but not at the Schiff base region. PMID- 26262962 TI - Direct Spectroscopic Evidence of Photoisomerization in para-Methoxy Methylcinnamate Revealed by Low-Temperature Matrix-Isolation FTIR Spectroscopy. AB - The photoisomerization of para-methoxy methylcinnamate (p-MMC) has been studied by low-temperature matrix-isolation FTIR spectroscopy. In particular, the difference spectrum of the mid-IR frequency region (1100-1800 cm(-1)) allows us to distinguish the structural change before and after ultraviolet (UV) light irradiation at >=300 nm and to convince that the cis-isomer is produced from the trans-isomer by comparing with the calculated IR spectra. Additionally, a reversible isomerization of p-MMC is demonstrated upon a sequential irradiation with different wavelengths of UV light. These findings provide a new insight into the electronic excited-state dynamics of p-MMC. PMID- 26262963 TI - Why Pt Survives but Pd Suffers From SOx Poisoning? AB - Pd is more prone to sulfation compared to Pt. Given the chemical similarity between Pt and Pd, the radical divide in their tendencies for sulfation remains a puzzle. We explain this intriguing difference using an extensive first-principles thermodynamics analysis and computed bulk and surface phase diagrams. In practically relevant temperatures and O2 and SO3 partial pressures, we find that Pt and Pd show significantly different tendencies for oxidation and sulfation. PdO formation is favored even at low oxygen chemical potential; however, PtO2 formation is not favorable in catalytically relevant conditions. Similarly, PdSO4, and adsorbed SO3 and oxygen species on clean and oxidized surfaces are highly favored, whereas PtSO4 formation does not occur at typical temperature and pressure conditions. Finally, several descriptors are identified that correlate to heightened sulfation tendencies, such as the critical O chemical potential for bulk oxide and surface oxide formation, chemical potentials O and SO3 for bulk sulfate formation, and SO3 binding strength on metal surface-oxide layers, which can be used to explore promising sulfur resistant catalysts. PMID- 26262964 TI - Photon Antibunching in a Cyclic Chemical Reaction Scheme. AB - The direct observation of chemical reactions on the single-molecule level is an ultimate goal in single-molecule chemistry, which also includes kinetic analyses. To analyze the lifetime of reaction intermediates, very sophisticated excitation schemes are often required. Here we focus on the kinetic analysis of the ground state proton transfer within the photocycle of a photoacid. In detail, we demonstrate the determination of the bimolecular rate constant of this process with nanosecond resolution. The procedure relies on the exploration of a purely quantum-optical effect, namely, photon antibunching, and thus on evaluating interphoton arrival times to extract the reaction rate constant. PMID- 26262965 TI - Ferroelectricity of CH3NH3PbI3 Perovskite. AB - Ferroelectricity has been believed to be an important but controversial origin of the excellent photovoltaic performance of organometal trihalide perovskites (OTPs). Here we investigate the ferroelectricity of a prototype OTP, CH3NH3PbI3 (MAPbI3), both theoretically and experimentally. Our first-principles calculations based on 3-D periodic boundary conditions reveal that a ferroelectric structure with polarization of ~8 MUC/cm(2) is the globally stable one among all possible tetragonal structures; however, experimentally no room temperature ferroelectricity is observed by using polarization-electric field hysteresis measurements and piezoresponse force microscopy. The discrepancy between our theoretical and experimental results is attributed to the dynamic orientational disorder of MA(+) groups and the semiconducting nature of MAPbI3 at room temperature. Therefore, we conclude that MAPbI3 is not ferroelectric at room temperature; however, it is possible to induce and experimentally observe apparent ferroelectric behavior through our proposed ways. Our results clarify the controversy of the ferroelectricity in MAPbI3 and also provide valuable guidance for future studies on this active topic. PMID- 26262967 TI - Open Source and Open Data Should Be Standard Practices. PMID- 26262966 TI - Investigation of the Ice-Binding Site of an Insect Antifreeze Protein Using Sum Frequency Generation Spectroscopy. AB - We study the ice-binding site (IBS) of a hyperactive antifreeze protein from the beetle Dendroides canadensis (DAFP-1) using vibrational sum-frequency generation spectroscopy. We find that DAFP-1 accumulates at the air-water interface due to the hydrophobic character of its threonine-rich IBS while retaining its highly regular beta-helical fold. We observe a narrow band at 3485 cm(-1) that we assign to the O-H stretch vibration of threonine hydroxyl groups of the IBS. The narrow character of the 3485 cm(-1) band suggests that the hydrogen bonds between the threonine residues at the IBS and adjacent water molecules are quite similar in strength, indicating that the IBS of DAFP-1 is extremely well-ordered, with the threonine side chains showing identical rotameric confirmations. The hydrogen bonded water molecules do not form an ordered ice-like layer, as was recently observed for the moderate antifreeze protein type III. It thus appears that the antifreeze action of DAFP-1 does not require the presence of ordered water but likely results from the direct binding of its highly ordered array of threonine residues to the ice surface. PMID- 26262968 TI - Rapid Energy Transfer Enabling Control of Emission Polarization in Perylene Bisimide Donor-Acceptor Triads. AB - Materials showing rapid intramolecular energy transfer and polarization switching are of interest for both their fundamental photophysics and potential for use in real-world applications. Here, we report two donor-acceptor-donor triad dyes based on perylene-bisimide subunits, with the long axis of the donors arranged either parallel or perpendicular to that of the central acceptor. We observe rapid energy transfer (<2 ps) and effective polarization control in both dye molecules in solution. A distributed-dipole Forster model predicts the excitation energy transfer rate for the linearly arranged triad but severely underestimates it for the orthogonal case. We show that the rapid energy transfer arises from a combination of through-bond coupling and through-space transfer between donor and acceptor units. As they allow energy cascading to an excited state with controllable polarization, these triad dyes show high potential for use in luminescent solar concentrator devices. PMID- 26262970 TI - Guest-Induced Emergent Properties in Metal-Organic Frameworks. AB - Metal-organic frameworks (MOFs) are crystalline nanoporous materials comprised of organic electron donors linked to metal ions by strong coordination bonds. Applications such as gas storage and separations are currently receiving considerable attention, but if the unique properties of MOFs could be extended to electronics, magnetics, and photonics, the impact on material science would greatly increase. Recently, we obtained "emergent properties," such as electronic conductivity and energy transfer, by infiltrating MOF pores with "guest" molecules that interact with the framework electronic structure. In this Perspective, we define a path to emergent properties based on the Guest@MOF concept, using zinc-carboxylate and copper-paddlewheel MOFs for illustration. Energy transfer and light harvesting are discussed for zinc carboxylate frameworks infiltrated with triplet-scavenging organometallic compounds and thiophene- and fullerene-infiltrated MOF-177. In addition, we discuss the mechanism of charge transport in TCNQ-infiltrated HKUST-1, the first MOF with electrical conductivity approaching conducting organic polymers. These examples show that guest molecules in MOF pores should be considered not merely as impurities or analytes to be sensed but also as an important aspect of rational design. PMID- 26262969 TI - Another Look at the Mechanisms of Hydride Transfer Enzymes with Quantum and Classical Transition Path Sampling. AB - The mechanisms involved in enzymatic hydride transfer have been studied for years, but questions remain due, in part, to the difficulty of probing the effects of protein motion and hydrogen tunneling. In this study, we use transition path sampling (TPS) with normal mode centroid molecular dynamics (CMD) to calculate the barrier to hydride transfer in yeast alcohol dehydrogenase (YADH) and human heart lactate dehydrogenase (LDH). Calculation of the work applied to the hydride allowed for observation of the change in barrier height upon inclusion of quantum dynamics. Similar calculations were performed using deuterium as the transferring particle in order to approximate kinetic isotope effects (KIEs). The change in barrier height in YADH is indicative of a zero point energy (ZPE) contribution and is evidence that catalysis occurs via a protein compression that mediates a near-barrierless hydride transfer. Calculation of the KIE using the difference in barrier height between the hydride and deuteride agreed well with experimental results. PMID- 26262971 TI - Enhanced Photogeneration of Polaron Pairs in Neat Semicrystalline Donor-Acceptor Copolymer Films via Direct Excitation of Interchain Aggregates. AB - We investigate the photogeneration of polaron pairs (PPs) in neat films of the semicrystalline donor-acceptor semiconducting copolymer PCPDTBT. Carefully selecting the solution-processing procedures, we obtain films with different amounts of crystallinity and interchain aggregation. We compare the photogeneration of PPs between the films by monitoring their photoinduced absorption in ultrafast pump-probe experiments, selectively exciting nonaggregated or aggregated polymer chains. The direct photoexcitation of interchain pi-aggregates results in prompt (<100 fs) charge generation. Compared to the case where nonaggregated chains are excited, we find an 8-fold increase in the prompt PP to singlet-exciton ratio. We also show that highly crystalline lamellar nanostructures not containing pi-stacked or any light-absorbing aggregates do not improve the efficiency of PP photogeneration. Our results show that light absorption from interchain aggregates is highly beneficial for charge photogeneration in semiconducting polymers and should be taken into account when optimizing film morphologies for photovoltaic devices. PMID- 26262972 TI - Formation of Water Chains on CaO(001): What Drives the 1D Growth? AB - Formation of partly dissociated water chains is observed on CaO(001) films upon water exposure at 300 K. While morphology and orientation of the 1D assemblies are revealed from scanning tunneling microscopy, their atomic structure is identified with infrared absorption spectroscopy combined with density functional theory calculations. The latter exploit an ab initio genetic algorithm linked to atomistic thermodynamics to determine low-energy H2O configurations on the oxide surface. The development of 1D structures on the C4v symmetric CaO(001) is triggered by symmetry-broken water tetramers and a favorable balance between adsorbate-adsorbate versus adsorbate-surface interactions at the constraint of the CaO lattice parameter. PMID- 26262973 TI - Tetracene Aggregation on Polar and Nonpolar Surfaces: Implications for Singlet Fission. AB - In molecular crystals that exhibit singlet fission, quantum yields depend strongly on intermolecular configurations that control the relevant electronic couplings. Here, we explore how noncovalent interactions between molecules and surfaces stabilize intermolecular structures with strong singlet fission couplings. Using molecular dynamics simulations, we studied the aggregation patterns of tetracene molecules on a solid surface as a function of surface polarity. Even at low surface concentrations, tetracene self-assembled into nanocrystallites where about 10-20% of the clustered molecules were part of at least one herringbone structure. The herringbone structure is the native structure of crystalline tetracene, which exhibits a high singlet fission quantum yield. Increasing the polarity of the surface reduced both the amount of clustering and the relative number of herringbone configurations, but only when the dipoles on the surface were orientationally disordered. These results have implications for the application of singlet fission in dye-sensitized solar cells. PMID- 26262974 TI - Resonance Femtosecond-Stimulated Raman Spectroscopy without Actinic Excitation Showing Low-Frequency Vibrational Activity in the S2 State of All-Trans beta Carotene. AB - Raman scattering with stimulating femtosecond probe pulses (FSR) was used to observe vibrational activity of all-trans beta-carotene in n-hexane. The short lived excited electronic state S2 was accessed in two ways: (i) by transient FSR after an actinic pulse to populate the S2 state, exploiting resonance from an Sx <- S2 transition, and (ii) by FSR without actinic excitation, using S2 <-> S0 resonance exclusively and narrow-band Raman/broad-band femtosecond probe pulses only. The two approaches have nonlinear optical susceptibilities chi((5)) and chi((3)), respectively. Both methods show low-frequency bands of the S2 state at 200, 400, and ~600 cm(-1), which are reported for the first time. With (ii) the intensities of low-frequency vibrational resonances in S2 are larger compared to those in S0, implying strong anharmonicities/mode mixing in the excited state. In principle, for short-lived electronic states, the chi((3)) method should allow the best characterization of low-frequency modes. PMID- 26262975 TI - Open Access: What Problem Are You Trying to Solve? PMID- 26262977 TI - ACS Is Open. PMID- 26262976 TI - X-ray Crystal Structure of Au38-xAgx(SCH2CH2Ph)24 Alloy Nanomolecules. AB - Herein, we report the X-ray crystallographic structure of a 38-metal atom Au-Ag alloy nanomolecule. The structure of monometallic Au38(SR)24 consists of 2 central Au atoms and 21 Au atoms forming a bi-icosahedral core protected by 6 dimeric and 3 monomeric units. In Au38-xAgx(SR)24,where x ranges from 1 to 5, the silver atoms are selectively incorporated into the Au21 bi-icosahedral core. Within the Au21 core, the silver atoms preferentially occupy nine selected locations: (a) the two vertex edges, three atoms on each edge and six atoms total, and (b) the middle face-shared three-atom ring, adding to a total of nine locations. X-ray crystallography yielded a composition of Au34.04Ag3.96(SCH2CH2Ph)24. The crystal structure of the alloy nanomolecule can be described in terms of shells as Au2@Au17.04Ag3.96@ 6*[-SR-Au-SR-Au-SR] 3*[-SR Au-SR-]. PMID- 26262979 TI - Open Access Debate: On the Flip Side. PMID- 26262978 TI - Unraveling the Mechanism of Photoinduced Charge Transfer in Carotenoid-Porphyrin C60 Molecular Triad. AB - Photoinduced charge transfer (CT) plays a central role in biologically significant systems and in applications that harvest solar energy. We investigate the relationship of CT kinetics and conformation in a molecular triad. The triad, consisting of carotenoid, porphyrin, and fullerene is structurally flexible and able to acquire significantly varied conformations under ambient conditions. With an integrated approach of quantum calculations and molecular dynamics simulations, we compute the rate of CT at two distinctive conformations. The linearly extended conformation, in which the donor (carotenoid) and the acceptor (fullerene) are separated by nearly 50 A, enables charge separation through a sequential CT process. A representative bent conformation that is entropically dominant, however, attenuates the CT, although the donor and the acceptor are spatially closer. Our computed rate of CT at the linear conformation is in good agreement with measured values. Our work provides unique fundamental understanding of the photoinduced CT process in the molecular triad. PMID- 26262980 TI - Minimal Model of Quantum Kinetic Clusters for the Energy-Transfer Network of a Light-Harvesting Protein Complex. AB - The energy absorbed in a light-harvesting protein complex is often transferred collectively through aggregated chromophore clusters. For population evolution of chromophores, the time-integrated effective rate matrix allows us to construct quantum kinetic clusters quantitatively and determine the reduced cluster-cluster transfer rates systematically, thus defining a minimal model of energy-transfer kinetics. For Fenna-Matthews-Olson (FMO) and light-havrvesting complex II (LCHII) monomers, quantum Markovian kinetics of clusters can accurately reproduce the overall energy-transfer process in the long-time scale. The dominant energy transfer pathways are identified in the picture of aggregated clusters. The chromophores distributed extensively in various clusters can assist a fast and long-range energy transfer. PMID- 26262981 TI - How Open Is Open Access? PMID- 26262982 TI - Stabilization of the Trigonal High-Temperature Phase of Formamidinium Lead Iodide. AB - Formamidinium lead iodide (FAPbI3) has the potential to achieve higher performance than established perovskite solar cells like methylammonium lead iodide (MAPbI3), while maintaining a higher stability. The major drawback for the latter material is that it can crystallize at room temperature in a wide bandgap hexagonal symmetry (P63mc) instead of the desired trigonal (P3m1) black phase formed at a higher temperature (130 degrees C). Our results show that employing a mixture of MAI and FAI in films deposited via a two-step approach, where the MAI content is <20%, results in the exchange of FA molecules with MA without any significant lattice shrinkage. Additionally, we show with temperature-dependent X ray diffraction that the trigonal phase exhibits no phase changes in the temperature range studied (25 to 250 degrees C). We attribute the stabilization of the structure to stronger interactions between the MA cation and the inorganic cage. Finally, we show that the inclusion of this small amount of MA also has a positive effect on the lifetime of the photoexcited species and results in more efficient devices. PMID- 26262983 TI - Trade-Offs in Capacity and Rechargeability in Nonaqueous Li-O2 Batteries: Solution-Driven Growth versus Nucleophilic Stability. AB - The development of high-capacity rechargeable Li-O2 batteries requires the identification of stable solvents that can promote a solution-based discharge mechanism, which has been shown to result in higher discharge capacities. Solution-driven discharge product growth requires dissolution of the adsorbed intermediate LiO2*, thus generating solvated Li+ and O2(-) ions. Such a mechanism is possible in solvents with high Gutmann donor or acceptor numbers. However, O2( ) is a strong nucleophile and is known to attack solvents via proton/hydrogen abstraction or substitution. This kind of a parasitic process is extremely detrimental to the battery's rechargeability. In this work, we develop a thermodynamic model to describe these two effects and demonstrate an anticorrelation between solvents' stability and their ability to enhance capacity via solution-mediated discharge product growth. We analyze the commonly used solvents in the same framework and describe why solvents that can promote higher discharge capacity are also prone to degradation. Solvating additives for practical Li-O2 batteries will have to be outliers to this observed anticorrelation. PMID- 26262984 TI - DNA Intercalated Psoralen Undergoes Efficient Photoinduced Electron Transfer. AB - The interaction of psoralens with DNA has been used for therapeutic and research purposes for decades. Still the photoinduced behavior of psoralens in DNA has never been observed directly. Femtosecond transient absorption spectroscopy is used here to gain direct insight into the photophysics of a DNA-intercalated psoralen (4'-aminomethyl-4,5',8-trimethyl-psoralen (AMT)). Intercalation reduces the excited singlet lifetime of AMT to 4 ps compared with 1400 ps for AMT in water. This singlet quenching prohibits the population of the triplet state that is accessed in free AMT. Instead, a DNA to AMT electron transfer takes place. The resulting radical pair decays primarily via charge recombination with a time constant of 30 ps. The efficient electron transfer observed here reveals a completely new aspect of the psoralen-DNA interaction. PMID- 26262985 TI - A Closer Look into Two-Step Perovskite Conversion with X-ray Scattering. AB - Recently, hybrid perovskites have gathered much interest as alternative materials for the fabrication of highly efficient and cost-competitive solar cells; however, many questions regarding perovskite crystal formation and deposition methods remain. Here we have applied a two-step protocol where a crystalline PbI2 precursor film is converted to MAPbI3-xClx perovskite upon immersion in a mixed solution of methylammonium iodide and methylammonium chloride. We have investigated both films with grazing incidence small-angle X-ray scattering to probe the inner film morphology. Our results demonstrate a strong link between lateral crystal sizes in the films before and after conversion, which we attribute to laterally confined crystal growth. Additionally, we observe an accumulation of smaller grains within the bulk in contrast with the surface. Thus, our results help to elucidate the crystallization process of perovskite films deposited via a two-step technique that is crucial for controlled film formation, improved reproducibility, and high photovoltaic performance. PMID- 26262986 TI - Synchronous Tricolor Emission-Based White Light from Quantum Dot Complex. AB - Herein we report the generation of synchronous tricolor emission for a single wavelength excitation from a quantum dot complex (QDC). The single-component QDC was formed out of a complexation reaction, at room temperature, between ligand free Mn(2+)-doped ZnS quantum dots (Qdots) and a mixture of two organic ligands (acetylsalicylic acid and 8-hydroxyquinoline). Furthermore, the tunability in chromaticity color coordinates, which is important for solid-state lighting, was achieved following the synthesis of QDC. Moreover, the photostable QDC emitted white light (lambdaex 320 nm) with (0.30, 0.33) and (0.32, 0.32) chromaticity color coordinates in the liquid and the solid phases, respectively. Hence, the white light-emitting QDC may be a superior material for light-emitting applications. PMID- 26262987 TI - Infrared Chemical Nano-Imaging: Accessing Structure, Coupling, and Dynamics on Molecular Length Scales. AB - This Perspective highlights recent advances in infrared vibrational chemical nano imaging. In its implementations of scattering scanning near-field optical microscopy (s-SNOM) and photothermal-induced resonance (PTIR), IR nanospectroscopy provides few-nanometer spatial resolution for the investigation of polymer, biomaterial, and related soft-matter surfaces and nanostructures. Broad-band IR s-SNOM with coherent laser and synchrotron sources allows for chemical recognition with small-ensemble sensitivity and the potential for sensitivity reaching the single-molecule limit. Probing selected vibrational marker resonances, it gives access to nanoscale chemical imaging of composition, domain morphologies, order/disorder, molecular orientation, or crystallographic phases. Local intra- and intermolecular coupling can be measured through frequency shifts of a vibrational marker in heterogeneous environments and associated inhomogeneities in vibrational dephasing. In combination with ultrafast spectroscopy, the vibrational coherent evolution of homogeneous sub ensembles coupled to their environment can be observed. Outstanding challenges are discussed in terms of extensions to coherent and multidimensional spectroscopies, implementation in liquid and in situ environments, general sample limitations, and engineering s-SNOM scanning probes to better control the nano localized optical excitation and to increase sensitivity. PMID- 26262988 TI - Understanding Open Access. PMID- 26262989 TI - Measuring Coherently Coupled Intramolecular Vibrational and Charge-Transfer Dynamics with Two-Dimensional Vibrational-Electronic Spectroscopy. AB - We demonstrate Fourier transform (FT) 2D vibrational-electronic (2D VE) spectroscopy employing a novel mid-IR and optical pulse sequence. This new femtosecond third-order nonlinear spectroscopy provides the high time and frequency resolutions of existing 2D FT techniques; however, resulting 2D VE spectra contain IR and electronic dipole moment cross terms. We use 2D VE spectroscopy to help understand the vibrational-electronic couplings in the cyanide-bridged transition-metal mixed valence complex [(CN)5Fe(II)CNRu(III)(NH3)5](-) dissolved in formamide. The amplitudes of the cross-peaks in the 2D VE spectra reveal that three of the intramolecular cyanide stretching vibrations lying along the charge-transfer axis are coherently coupled to the metal-to-metal charge-transfer electronic transition with differing strengths. Analysis of the 2D VE line shapes reveals positive and negative correlations of the cyanide stretching modes with the charge-transfer transition depending on the physical orientation of the vibration in the molecule and its interaction with the solvent. The insights found thus far into the vibronic couplings in the mixed valence model system indicate that the 2D VE technique will be a valuable addition to the existing multidimensional spectroscopy toolbox. PMID- 26262990 TI - Photostable Copper Nanoclusters: Compatible Forster Resonance Energy-Transfer Assays and a Nanothermometer. AB - To address the concern of material chemists over the issue of stability and photoluminescent (PL) characteristics of Cu nanoclusters (NCs), herein we present an efficient protocol discussing PL Cu NCs (Cu/HSA) having blue emission and high photostability. These PL NCs were illustrated as efficient probes for Forster resonance energy transfer (FRET) with a compatible fluorophore (Coumarin 153). Our spectroscopic results were well complemented by our molecular docking calculations, which also favored our proposed mechanism for Cu NC formation. The beneficial aspect and uniqueness of these nontoxic Cu/HSA NCs highlights their temperature-dependent PL reversibility as well as the reversible FRET with Coumarin 153, which enables them to be used as a nanothermometer and a PL marker for sensitive biological samples. PMID- 26262992 TI - High Resolution Consensus Mapping of Quantitative Trait Loci for Fiber Strength, Length and Micronaire on Chromosome 25 of the Upland Cotton (Gossypium hirsutum L.). AB - Cotton (Gossypium hirsutum L.) is an important agricultural crop that provides renewable natural fiber resources for the global textile industry. Technological developments in the textile industry and improvements in human living standards have increased the requirement for supplies and better quality cotton. Upland cotton 0-153 is an elite cultivar harboring strong fiber strength genes. To conduct quantitative trait locus (QTL) mapping for fiber quality in 0-153, we developed a population of 196 recombinant inbred lines (RILs) from a cross between 0-153 and sGK9708. The fiber quality traits in 11 environments were measured and a genetic linkage map of chromosome 25 comprising 210 loci was constructed using this RIL population, mainly using simple sequence repeat markers and single nucleotide polymorphism markers. QTLs were identified across diverse environments using the composite interval mapping method. A total of 37 QTLs for fiber quality traits were identified on chromosome 25, of which 17 were stably expressed in at least in two environments. A stable fiber strength QTL, qFS-chr25-4, which was detected in seven environments and was located in the marker interval between CRI-SNP120491 and BNL2572, could explain 6.53%-11.83% of the observed phenotypic variations. Meta-analysis also confirmed the above QTLs with previous reports. Application of these QTLs could contribute to improving fiber quality and provide information for marker-assisted selection. PMID- 26262991 TI - Antidiabetic Effect of Galantamine: Novel Effect for a Known Centrally Acting Drug. AB - The cholinergic anti-inflammatory pathway is one of the putative biochemical pathways that link diabetes with Alzheimer disease. Hence, we aimed to verify the potential antidiabetic effect of galantamine, unveil the possible mechanisms and evaluate its interaction with vildagliptin. The n5-STZ rat model was adopted and the diabetic animals were treated with galantamine and/or vildagliptin for 4 weeks. Galantamine lowered the n5-STZ-induced elevation in body weight, food/water intake, serum levels of glucose, fructosamine, and ALT/AST, as well as AChE in the tested organs. Moreover, it modulated successfully the lipid profile assessed in serum, liver, and muscle, and increased serum insulin level, as well as % beta-cell function, in a pattern similar to that of vildagliptin. Additionally, galantamine confirmed its antioxidant (Nrf2, TAC, MDA), anti inflammatory (NF-kappaB, TNF-alpha, visfatin, adiponectin) and anti-apoptotic (caspase-3, cytochrome c) capabilities by altering the n5-STZ effect on all the aforementioned parameters. On the molecular level, galantamine/vildagliptin have improved the insulin (p-insulin receptor, p-Akt, GLUT4/GLUT2) and Wnt/beta catenin (p-GSK-3beta, beta-catenin) signaling pathways. On almost all parameters, the galantamine effects surpassed that of vildagliptin, while the combination regimen showed the best effects. The present results clearly proved that galantamine modulated glucose/lipid profile possibly through its anti-oxidant, apoptotic, -inflammatory and -cholinesterase properties. These effects could be attributed partly to the enhancement of insulin and Wnt/beta-catenin signaling pathways. Galantamine can be strongly considered as a potential antidiabetic agent and as an add-on therapy with other oral antidiabetics. PMID- 26262993 TI - Early Detection of Myocardial Bioenergetic Deficits: A 9.4 Tesla Complete Non Invasive 31P MR Spectroscopy Study in Mice with Muscular Dystrophy. AB - BACKGROUND: Duchenne muscular dystrophy (DMD) is the most common fatal form of muscular dystrophy characterized by striated muscle wasting and dysfunction. Patients with DMD have a very high incidence of heart failure, which is increasingly the cause of death in DMD patients. We hypothesize that in the in vivo system, the dystrophic cardiac muscle displays bioenergetic deficits prior to any functional or structural deficits. To address this we developed a complete non invasive 31P magnetic resonance spectroscopy (31P MRS) approach to measure myocardial bioenergetics in the heart in vivo. METHODS AND RESULTS: Six control and nine mdx mice at 5 months of age were used for the study. A standard 3D Image Selected In vivo Spectroscopy (3D-ISIS) sequence was used to provide complete gradient controlled three-dimensional localization for heart 31P MRS. These studies demonstrated dystrophic hearts have a significant reduction in PCr/ATP ratio compare to normal (1.59+/-0.13 vs 2.37+/-0.25, p<0.05). CONCLUSION: Our present study provides the direct evidence of significant cardiac bioenergetic deficits in the in vivo dystrophic mouse. These data suggest that energetic defects precede the development of significant hemodynamic or structural changes. The methods provide a clinically relevant approach to use myocardial energetics as an early marker of disease in the dystrophic heart. The new method in detecting the in vivo bioenergetics abnormality as an early non invasive marker of emerging dystrophic cardiomyopathy is critical in management of patients with DMD, and optimized therapies aimed at slowing or reversing the cardiomyopathy. PMID- 26262994 TI - A Rare Association of Sinus Venosus-Type Atrial Septal Defect and Persistent Left Superior Vena Cava Detected by Transthoracic Echocardiography and Cardiac Magnetic Resonance Imaging. AB - BACKGROUND: Association of persistent left superior vena cava (PLSVC) and sinus venosus-type atrial septal defect (SVASD) is rare. We describe a patient with dilated coronary sinus (CS) found to have PLSVC and SVASD. CASE REPORT: The patient is a 60-year-old man with history of stroke who underwent a transthoracic echocardiogram (TTE) for evaluation of shortness of breath. TTE demonstrated a markedly dilated CS. Agitated saline was injected into the left antecubital vein to further assess CS. The parasternal long axis view demonstrated immediate filling of the CS and confirmed the presence of a PLSVC. Apical 4-chamber view with injection of agitated saline into the right antecubital vein demonstrated immediate contrast opacification of both atria, consistent with a right to left cardiac shunt. Cardiac magnetic resonance (CMR) was performed, which confirmed the TTE findings of PLSVC and defined the cardiac shunt as SVASD. CONCLUSIONS: PLSVC should be suspected in a patient with an abnormally dilated CS. In this case we identified a rare association of PLSVC with a SVASD. TTE with agitated saline contrast injection and CMR are useful diagnostic tools for PLSVC and associated cardiac congenital anomalies, respectively. PMID- 26262995 TI - Case-Mix, Care Processes, and Outcomes in Medically-Ill Patients Receiving Mechanical Ventilation in a Low-Resource Setting from Southern India: A Prospective Clinical Case Series. AB - BACKGROUND: Mechanical ventilation is a resource intensive organ support treatment, and historical studies from low-resource settings had reported a high mortality. We aimed to study the outcomes in patients receiving mechanical ventilation in a contemporary low-resource setting. METHODS: We prospectively studied the characteristics and outcomes (disease-related, mechanical ventilation related, and process of care-related) in 237 adults mechanically ventilated for a medical illness at a teaching hospital in southern India during February 2011 to August 2012. Vital status of patients discharged from hospital was ascertained on Day 90 or later. RESULTS: Mean age of the patients was 40 +/- 17 years; 140 (51%) were men. Poisoning and envenomation accounted for 98 (41%) of 237 admissions. In total, 87 (37%) patients died in-hospital; 16 (7%) died after discharge; 115 (49%) were alive at 90-day assessment; and 19 (8%) were lost to follow-up. Weaning was attempted in 171 (72%) patients; most patients (78 of 99 [79%]) failing the first attempt could be weaned off. Prolonged mechanical ventilation was required in 20 (8%) patients. Adherence to head-end elevation and deep vein thrombosis prophylaxis were 164 (69%) and 147 (62%) respectively. Risk of nosocomial infections particularly ventilator-associated pneumonia was high (57.2 per 1,000 ventilator-days). Higher APACHE II score quartiles (adjusted HR [95% CI] quartile 2, 2.65 [1.19-5.89]; quartile 3, 2.98 [1.24-7.15]; quartile 4, 5.78 [2.45-13.60]), and new-onset organ failure (2.98 [1.94-4.56]) were independently associated with the risk of death. Patients with poisoning had higher risk of reintubation (43% vs. 20%; P = 0.001) and ventilator-associated pneumonia (75% vs. 53%; P = 0.001). But, their mortality was significantly lower compared to the rest (24% vs. 44%; P = 0.002). CONCLUSIONS: The case-mix considerably differs from other settings. Mortality in this low-resource setting is similar to high resource settings. But, further improvements in care processes and prevention of nosocomial infections are required. PMID- 26262996 TI - Effects of N-acetylcysteine, oral glutathione (GSH) and a novel sublingual form of GSH on oxidative stress markers: A comparative crossover study. AB - Glutathione (GSH) is critical to fight against oxidative stress. Its very low bioavailability limits the interest of a supplementation. The purpose of this study was to compare the bioavailability, the effect on oxidative stress markers and the safety of a new sublingual form of GSH with two commonly used dietary supplements, N-acetylcysteine (NAC) and oral GSH. The study was a three-week randomized crossover trial. 20 Volunteers with metabolic syndrome were enrolled. GSH levels and several oxidative stress markers were determined at different times during each 21-days period. Compared to oral GSH group, an increase of total and reduced GSH levels in plasma and a higher GSH/GSSG ratio (p=0.003) was observed in sublingual GSH group. After 3 weeks of administration, there was a significant increase of vitamin E level in plasma only in sublingual GSH group (0.83 umol/g; p=0.04). Our results demonstrate the superiority of a new sublingual form of GSH over the oral GSH form and NAC in terms of GSH supplementation. PMID- 26262999 TI - The impact and dissemination of scientific research: From impact factor to social media. The Top 10 articles in Epilepsy & Behavior published in 2014. PMID- 26262997 TI - Quantitative combination of natural anti-oxidants prevents metabolic syndrome by reducing oxidative stress. AB - Insulin resistance and abdominal obesity are present in the majority of people with the metabolic syndrome. Antioxidant therapy might be a useful strategy for type 2 diabetes and other insulin-resistant states. The combination of vitamin C (Vc) and vitamin E has synthetic scavenging effect on free radicals and inhibition effect on lipid peroxidation. However, there are few studies about how to define the best combination of more than three anti-oxidants as it is difficult or impossible to test the anti-oxidant effect of the combination of every concentration of each ingredient experimentally. Here we present a math model, which is based on the classical Hill equation to determine the best combination, called Fixed Dose Combination (FDC), of several natural anti oxidants, including Vc, green tea polyphenols (GTP) and grape seed extract proanthocyanidin (GSEP). Then we investigated the effects of FDC on oxidative stress, blood glucose and serum lipid levels in cultured 3T3-L1 adipocytes, high fat diet (HFD)-fed rats which serve as obesity model, and KK-ay mice as diabetic model. The level of serum malondialdehyde (MDA) in the treated rats was studied and Hematoxylin-Eosin (HE) staining or Oil red slices of liver and adipose tissue in the rats were examined as well. FDC shows excellent antioxidant and anti glycation activity by attenuating lipid peroxidation. FDC determined in this investigation can become a potential solution to reduce obesity, to improve insulin sensitivity and be beneficial for the treatment of fat and diabetic patients. It is the first time to use the math model to determine the best ratio of three anti-oxidants, which can save much more time and chemical materials than traditional experimental method. This quantitative method represents a potentially new and useful strategy to screen all possible combinations of many natural anti-oxidants, therefore may help develop novel therapeutics with the potential to ameliorate the worldwide metabolic abnormalities. PMID- 26262998 TI - Influence of myeloperoxidase on colon tumor occurrence in inflamed versus non inflamed colons of Apc(Min/+) mice. AB - Control of colorectal cancer needs to be tailored to its etiology. Tumor promotion mechanisms in colitis-associated colon cancer differ somewhat from the mechanisms involved in hereditary and sporadic colorectal cancer. Unlike sporadic or inherited tumors, some experimental models show that colitis-associated colon tumors do not require cyclooxygenase (COX) expression for progression, and non steroidal anti-inflammatory drugs (NSAIDs) which prevent sporadic or inherited colon cancer do not prevent colitis-associated colon cancer. We report that myeloperoxidase (MPO), an ancestor of the COX isoenzymes, is a determinant of colitis-associated colon tumors in Apc(Min/+) mice. During experimentally induced colitis, inhibition of MPO by resorcinol dampened colon tumor development. Conversely, in the bowels of Apc(Min/+) mice without colitis, resorcinol administration or 'knockout' of MPO gene coincided with a slight, but discernible increase in colon tumor incidence. Acrolein, a by-product of MPO catalysis, formed a covalent adduct with the phosphatase tensin homolog (PTEN) tumor suppressor and enhanced the activity of the Akt kinase proto-oncogene in vitro and in vivo. Thus, MPO may be an important determinant of diet and inflammation on colon cancer risk via its effect on endogenous exposure to oxidants and acrolein. We propose a hypothetical model to explain an apparent dichotomy between colon tumor occurrence and MPO inhibition in inflamed versus non-inflamed colons. PMID- 26263000 TI - Categorical Perception of Fear and Anger Expressions in Whole, Masked and Composite Faces. AB - Human observers are remarkably proficient at recognizing expressions of emotions and at readily grouping them into distinct categories. When morphing one facial expression into another, the linear changes in low-level features are insufficient to describe the changes in perception, which instead follow an s shaped function. Important questions are, whether there are single diagnostic regions in the face that drive categorical perception for certain parings of emotion expressions, and how information in those regions interacts when presented together. We report results from two experiments with morphed fear anger expressions, where (a) half of the face was masked or (b) composite faces made up of different expressions were presented. When isolated upper and lower halves of faces were shown, the eyes were found to be almost as diagnostic as the whole face, with the response function showing a steep category boundary. In contrast, the mouth allowed for a substantially lesser amount of accuracy and responses followed a much flatter psychometric function. When a composite face consisting of mismatched upper and lower halves was used and observers were instructed to exclusively judge either the expression of mouth or eyes, the to-be ignored part always influenced perception of the target region. In line with experiment 1, the eye region exerted a much stronger influence on mouth judgements than vice versa. Again, categorical perception was significantly more pronounced for upper halves of faces. The present study shows that identification of fear and anger in morphed faces relies heavily on information from the upper half of the face, most likely the eye region. Categorical perception is possible when only the upper face half is present, but compromised when only the lower part is shown. Moreover, observers tend to integrate all available features of a face, even when trying to focus on only one part. PMID- 26263001 TI - Identification of Predictive Early Biomarkers for Sterile-SIRS after Cardiovascular Surgery. AB - Systemic inflammatory response syndrome (SIRS) is a common complication after cardiovascular surgery that in severe cases can lead to multiple organ dysfunction syndrome and even death. We therefore set out to identify reliable early biomarkers for SIRS in a prospective small patient study for timely intervention. 21 Patients scheduled for planned cardiovascular surgery were recruited in the study, monitored for signs of SIRS and blood samples were taken to investigate biomarkers at pre-assigned time points: day of admission, start of surgery, end of surgery, days 1, 2, 3, 5 and 8 post surgery. Stored plasma and cryopreserved blood samples were analyzed for cytokine expression (IL1beta, IL2, IL6, IL8, IL10, TNFalpha, IFNgamma), other pro-inflammatory markers (sCD163, sTREM-1, ESM-1) and response to endotoxin. Acute phase proteins CRP, PCT and pro inflammatory cytokines IL6 and IL8 were significantly increased (p<0.001) at the end of surgery in all patients but could not distinguish between groups. Normalization of samples revealed significant increases in IL1beta changes (p<0.05) and decreased responses to endotoxin (p<0.01) in the SIRS group at the end of surgery. Soluble TREM-1 plasma concentrations were significantly increased in patients with SIRS (p<0.01). This small scale patient study could show that common sepsis markers PCT, CRP, IL6 and TNFalpha had low predictive value for early diagnosis of SIRS after cardiovascular surgery. A combination of normalized IL1beta plasma levels, responses to endotoxin and soluble TREM-1 plasma concentrations at the end of surgery are predictive markers of SIRS development in this small scale study and could act as an indicator for starting early therapeutic interventions. PMID- 26263003 TI - Physico-chemical characterization of pine cone shell and its use as biosorbent and fuel. AB - Physico-chemical properties of pine cone shell have been determined. Results of characterization study showed that pine cone shell could be used as biosorbent of nickel from aqueous solutions in a fixed-bed column and later as input material in thermochemical processes. To study the behavior of Ni-loaded pine cone shell as fuel, non-isothermal thermogravimetric tests were performed. These tests showed that, in nitrogen atmosphere, the main decomposition occurs from 200 degrees C to 500 degrees C and, in oxidant atmosphere, the behavior is of type "combustion+pyrolysis" (at higher temperatures there is a clear decomposition of residue formed during the initial steps). Finally, the effect of the presence of Ni was analyzed. Thermogravimetric curves did not change their profile and the total amount of nickel was detected in char-ash fraction and not in flue gases. These results suggest that nickel does not form volatile compounds at considered operational conditions. PMID- 26263002 TI - Parasporin-2 from a New Bacillus thuringiensis 4R2 Strain Induces Caspases Activation and Apoptosis in Human Cancer Cells. AB - In previous studies, parasporin-2Aa1, originally isolated from Bacillus thuringiensis strain A1547, was shown to be cytotoxic against specific human cancer cells but the mechanisms of action were not studied. In the present study, we found that proteinase K activated parasporin-2Aa1 protein isolated from a novel B. thuringiensis strain, 4R2, was specifically cytotoxic to endometrial, colon, liver, cervix, breast and prostate cancer. It showed no toxicity against normal cells. Upon treatment with proteinase K-activated parasporin-2Aa1, morphological changes were observed and western blot analysis revealed the cleavage of poly (ADP-Ribose) polymerase, caspase-3 and caspase-9 in cancer cell lines exclusively, indicative of programmed cell death, apoptosis. Flow cytometry analyses,using propidium iodide and annexin V, as well as a caspases 3/7 assay confirmed apoptosis induction. Further analyses were performed to study survival pathways, including AKT, XIAP, ERK1/2 and PAR-4, a known inducer of apoptosis. These results indicate that parasporin-2Aa1 is a selective cytotoxic protein that induces apoptosis in various human cancer cell lines from diverse tissues. PMID- 26263004 TI - Removal of hexenuronic acid by xylanase to reduce adsorbable organic halides formation in chlorine dioxide bleaching of bagasse pulp. AB - Xylanase-aided chlorine dioxide bleaching of bagasse pulp was investigated. The pulp was pretreated with xylanase and followed a chlorine dioxide bleaching stage. The ATR-FTIR and XPS were employed to determine the surface chemistry of the control pulp, xylanase treated and chlorine dioxide treated pulps. The hexenuronic acid (HexA) could obviously be reduced after xylanase pretreatment, and the adsorbable organic halides (AOX) were reduced after chlorine dioxide bleaching. Compared to the control pulp, AOX could be reduced by 21.4-26.6% with xylanase treatment. Chlorine dioxide demand could be reduced by 12.5-22% to achieve the same brightness. The ATR-FTIR and XPS results showed that lignin and hemicellulose (mainly HexA) were the main source for AOX formation. Xylanase pretreatment could remove HexA and expose more lignin, which decreased the chlorine dioxide demand and thus reduced formation of AOX. PMID- 26263005 TI - Production of short-chain fatty acids from the biodegradation of wheat straw lignin by Aspergillus fumigatus. AB - The wheat straw lignin-rich fraction (WSLig-RF) can be used as a raw material for the production of metabolites for industrial use if ligninolytic mitosporic fungi are used for its biodegradation into aromatics and short-chain fatty acids (SCFAs, i.e., SCFA2-6). Although methods for the production of SCFA2-6 have been described previously, quantitative data of SCFA2-6 production have not been reported. The objectives of this study were to investigate the biodegradation of different concentrations of WSLig-RF by Aspergillus fumigatus and to identify whether SCFA2-6 production was dependent on the concentration of aromatics. A. fumigatus generated 2805mgL(-1) acetic acid when mixed with WSLig-RF at a concentration of 20gL(-1). Thus, aromatics are a substrate for the biosynthesis of SCFA2-6, and their production depends on the concentration of WSLig-RF aromatics. PMID- 26263006 TI - GDSCalc: A Web-Based Application for Evaluating Discrete Graph Dynamical Systems. AB - Discrete dynamical systems are used to model various realistic systems in network science, from social unrest in human populations to regulation in biological networks. A common approach is to model the agents of a system as vertices of a graph, and the pairwise interactions between agents as edges. Agents are in one of a finite set of states at each discrete time step and are assigned functions that describe how their states change based on neighborhood relations. Full characterization of state transitions of one system can give insights into fundamental behaviors of other dynamical systems. In this paper, we describe a discrete graph dynamical systems (GDSs) application called GDSCalc for computing and characterizing system dynamics. It is an open access system that is used through a web interface. We provide an overview of GDS theory. This theory is the basis of the web application; i.e., an understanding of GDS provides an understanding of the software features, while abstracting away implementation details. We present a set of illustrative examples to demonstrate its use in education and research. Finally, we compare GDSCalc with other discrete dynamical system software tools. Our perspective is that no single software tool will perform all computations that may be required by all users; tools typically have particular features that are more suitable for some tasks. We situate GDSCalc within this space of software tools. PMID- 26263007 TI - Vitamin D, precocious acute myocardial infarction, and exceptional longevity. PMID- 26263008 TI - Low-level carotid baroreceptor stimulation: a promising feasible modulator for ventricular and atrial arrhythmias. PMID- 26263009 TI - Strategy in managing anticoagulation therapy following prosthetic heart valve replacement in a patient with dengue fever. PMID- 26263010 TI - Tricuspid systolic peak velocity is a prognostic factor in patients with cystic fibrosis. PMID- 26263011 TI - Low-level vagus nerve stimulation: an important therapeutic option for atrial fibrillation treatment via modulating cardiac autonomic tone. PMID- 26263012 TI - In vivo validation of an oscillometric method for estimating central aortic pressure. PMID- 26263013 TI - Does Hair Dye Use Increase the Risk of Breast Cancer? A Population-Based Case Control Study of Finnish Women. AB - INTRODUCTION: Role of hair dyes in the etiology of breast cancer has occasionally raised concern but previous research has concluded with mixed results. Remnants of prohibited aromatic amines have been found in many hair dye products, and elevated levels of DNA-adducts of these amines have been detected from breast epithelial cells of hair dye users. However, the IARC working group has concluded that there is inadequate evidence for carcinogenicity of personal hair dye use and limited evidence in experimental animals for carcinogenicity of hair colorants. MATERIAL AND METHODS: We investigated whether the use of hair dyes is associated with breast cancer risk in women. The study design was a retrospective population-based case-control study in Finland, with a self-administered questionnaire from 6,567 breast cancer patients, aged 22-60 years and diagnosed in 2000-2007, and their 21,598 matched controls. We report odds ratios (OR) with 95% confidence interval (95% CI) from a conditional logistic regression model applied to the frequency matched sets of cases and controls. Bias-adjusted odds ratios from the sensitivity analysis are also presented. RESULTS: After adjusting for potential confounders, the odds of breast cancer increased by 23% (OR: 1.23, 95% CI: 1.11-1.36) among women who used hair dyes compared to those who did not. In women born before 1950 an increase of 28% was noted (OR: 1.28, 95% CI: 1.10 1.48). We also observed a significant trend between the OR and cumulative use of hair dyes (P: 0.005). Bias-adjusted odds ratios varied between 1.04 and 2.50. CONCLUSIONS: Our results suggest that use of hair dyes is associated with breast cancer incidence. The impact on public health may be substantial due to vast popularity of hair coloring in modern societies. It should be noted that regardless of all efforts, a possibility of bias cannot definitively be ruled out and use of a prospective design is warranted. Based on the present results, it may be concluded however that safety of hair dyes in relation to breast cancer cannot yet be fully acknowledged and lack of external safety assessment within the cosmetics industry is of major concern. PMID- 26263015 TI - A Haptic Feedback Scheme to Accurately Position a Virtual Wrist Prosthesis Using a Three-Node Tactor Array. AB - In this paper, a novel haptic feedback scheme, used for accurately positioning a 1DOF virtual wrist prosthesis through sensory substitution, is presented. The scheme employs a three-node tactor array and discretely and selectively modulates the stimulation frequency of each tactor to relay 11 discrete haptic stimuli to the user. Able-bodied participants were able to move the virtual wrist prosthesis via a surface electromyography based controller. The participants evaluated the feedback scheme without visual or audio feedback and relied solely on the haptic feedback alone to correctly position the hand. The scheme was evaluated through both normal (perpendicular) and shear (lateral) stimulations applied on the forearm. Normal stimulations were applied through a prototype device previously developed by the authors while shear stimulations were generated using an ubiquitous coin motor vibrotactor. Trials with no feedback served as a baseline to compare results within the study and to the literature. The results indicated that using normal and shear stimulations resulted in accurately positioning the virtual wrist, but were not significantly different. Using haptic feedback was substantially better than no feedback. The results found in this study are significant since the feedback scheme allows for using relatively few tactors to relay rich haptic information to the user and can be learned easily despite a relatively short amount of training. Additionally, the results are important for the haptic community since they contradict the common conception in the literature that normal stimulation is inferior to shear. From an ergonomic perspective normal stimulation has the potential to benefit upper limb amputees since it can operate at lower frequencies than shear-based vibrotactors while also generating less noise. Through further tuning of the novel haptic feedback scheme and normal stimulation device, a compact and comfortable sensory substitution device for upper limb amputees might be created. PMID- 26263014 TI - Efficacy of Intrauterine Bakri Balloon Tamponade in Cesarean Section for Placenta Previa Patients. AB - PURPOSE: The aims of this study were to analyze the predictive factors for the use of intrauterine balloon insertion and to evaluate the efficacy and factors affecting failure of uterine tamponade with a Bakri balloon during cesarean section for abnormal placentation. METHODS: We reviewed the medical records of 137 patients who underwent elective cesarean section for placenta previa between July 2009 and March 2014. Cesarean section and Bakri balloon insertion were performed by a single qualified surgeon. The Bakri balloon was applied when blood loss during cesarean delivery exceeded 1,000 mL. RESULTS: Sixty-four patients (46.7%) required uterine balloon tamponade during cesarean section due to postpartum bleeding from the lower uterine segment, of whom 50 (78.1%) had placenta previa totalis. The overall success rate was 75% (48/64) for placenta previa patients. Previous cesarean section history, anterior placenta, peripartum platelet count, and disseminated intravascular coagulopathy all significantly differed according to balloon success or failure (all p<0.05). The drainage amount over 1 hour was 500 mL (20-1200 mL) in the balloon failure group and 60 mL (5-500 mL) in the balloon success group (p<0.01). CONCLUSION: Intrauterine tamponade with a Bakri balloon is an adequate adjunct management for postpartum hemorrhage following cesarean section for placenta previa to preserve the uterus. This method is simple to apply, non-invasive, and inexpensive. However, possible factors related to failure of Bakri balloon tamponade for placenta previa patients such as prior cesarean section history, anterior placentation, thrombocytopenia, presence of DIC at the time of catheter insertion, and catheter drainage volume more than 500 mL within 1 hour of catheter placement should be recognized, and the next-line management should be prepared in advance. PMID- 26263018 TI - Differences in the nutritional content of baby and toddler foods with front-of package nutrition claims issued by manufacturers v. governments/health organizations. AB - OBJECTIVE: Nutritional information panels are required on all packaged food products in the USA, yet are perceived as difficult to use by consumers. Nutritional symbols have been developed by various groups to assist consumers in making healthier food purchases. Different nutritional criteria are used depending on the authorizing body of these symbols. The present study assesses the nutrient profile of baby and toddler foods in light of their accompanying nutritional symbols. DESIGN: Kruskal-Wallis and chi 2 tests were used to assess differences in the nutritional content of products based on the presence and issuing body of nutritional symbols. SETTING: Nine grocery, drug and department stores in Philadelphia, PA, USA. SUBJECTS: Two hundred and forty packaged baby and toddler foods. RESULTS: Products whose nutritional symbol was issued by government/health professionals contained significantly more Ca (P = 0.002), fibre (P = 0.001), protein (P = 0.005), vitamin A (P = 0.011), vitamin C (P < 0.001) and Zn (P < 0.001) and less sugar (P = 0.004) per serving than products without a nutritional symbol and products whose nutritional symbol was issued by the manufacturer. CONCLUSIONS: Products with a nutritional symbol issued by government/health professionals were healthier than foods with nutritional symbols issued by the manufacturer directly and foods with no nutritional symbols. PMID- 26263019 TI - Prediction of Nanoparticle and Colloid Attachment on Unfavorable Mineral Surfaces Using Representative Discrete Heterogeneity. AB - Despite several decades of research there currently exists no mechanistic theory to predict colloid attachment in porous media under environmental conditions where colloid-collector repulsion exists (unfavorable conditions for attachment). It has long been inferred that nano- to microscale surface heterogeneity (herein called discrete heterogeneity) drives colloid attachment under unfavorable conditions. Incorporating discrete heterogeneity into colloid-collector interaction calculations in particle trajectory simulations predicts colloid attachment under unfavorable conditions. As yet, discrete heterogeneity cannot be independently measured by spectroscopic or other approaches in ways directly relevant to colloid-surface interaction. This, combined with the fact that a given discrete heterogeneity representation will interact differently with differently sized colloids as well as different ionic strengths for a given sized colloid, suggests a strategy to back out representative discrete heterogeneity by a comparison of simulations to experiments performed across a range of colloid size, solution IS, and fluid velocity. This has recently been performed for interaction of carboxylate-modified polystyrene latex (CML) microsphere attachment to soda lime glass at pH 6.7 with NaCl electrolyte. However, extension to other surfaces, pH values, and electrolytes is needed. For this reason, the attachment of CML (0.25, 1.1, and 2.0 MUm diameters) from aqueous suspension onto a variety of unfavorable mineral surfaces (soda lime glass, muscovite, and albite) was examined for pH values of 6.7 and 8.0), fluid velocities (1.71 * 10( 3) and 5.94 * 10(-3) m s(-1)), IS (6.0 and 20 mM), and electrolytes (NaCl, CaSO4, and multivalent mixtures). The resulting representative heterogeneities (heterodomain size and surface coverage, where heterodomain refers to nano- to microscale attractive domains) yielded colloid attachment predictions that were compared to predictions from existing applicable semiempirical expressions in order to examine the strengths and weaknesses of the discrete heterogeneity approach and opportunities for improvement. PMID- 26263021 TI - Surface and Structural Investigation of a MnOx Birnessite-Type Water Oxidation Catalyst Formed under Photocatalytic Conditions. AB - Catalytically active MnOx species have been reported to form in situ from various Mn-complexes during electrocatalytic and solution-based water oxidation when employing cerium(IV) ammonium ammonium nitrate (CAN) oxidant as a sacrificial reagent. The full structural characterization of these oxides may be complicated by the presence of support material and lack of a pure bulk phase. For the first time, we show that highly active MnOx catalysts form without supports in situ under photocatalytic conditions. Our most active (4)MnOx catalyst (~0.84 mmol O2 mol Mn(-1) s(-1)) forms from a Mn4O4 bearing a metal-organic framework. (4)MnOx is characterized by pair distribution function analysis (PDF), Raman spectroscopy, and HR-TEM as a disordered, layered Mn-oxide with high surface area (216 m(2) g(-1)) and small regions of crystallinity and layer flexibility. In contrast, the (S)MnOx formed from Mn(2+) salt gives an amorphous species of lower surface area (80 m(2) g(-1)) and lower activity (~0.15 mmol O2 mol Mn(-1) s( 1)). We compare these catalysts to crystalline hexagonal birnessite, which activates under the same conditions. Full deconvolution of the XPS Mn2p3/2 core levels detects enriched Mn(3+) and Mn(2+) content on the surfaces, which indicates possible disproportionation/comproportionation surface equilibria. PMID- 26263022 TI - Seven weeks of Western diet in apolipoprotein-E-deficient mice induce metabolic syndrome and non-alcoholic steatohepatitis with liver fibrosis. AB - Non-alcoholic steatohepatitis (NASH) is characterised by hepatic steatosis, inflammation and fibrosis, which might progress to cirrhosis. Human NASH is associated with metabolic syndrome (MS). Currently, rodent NASH models either lack significant fibrosis or MS. ApoE(-/-) mice are a MS model used in cardiovascular research. The aim of this work was to establish and characterise a novel mouse NASH model with significant fibrosis and MS. ApoE(-/-) and wild-type mice (wt) were fed either a western-diet (WD), methionine-choline-deficient-diet (MCD) or normal chow. Liver histology, RT-PCR, hepatic hydroxyproline content, triglycerides and cholesterol levels, and fasting glucose levels assessed hepatic steatosis, inflammation and fibrosis. Further, portal pressure was measured invasively, and kidney pathology was assessed by histology. ApoE(-/-) mice receiving WD showed abnormal glucose tolerance, hepatomegaly, weight gain and full spectrum of NASH including hepatic steatosis, fibrosis and inflammation, with no sign of renal damage. MCD-animals showed less severe liver fibrosis, but detectable renal pathological changes, besides weight loss and unchanged glucose tolerance. This study describes a murine NASH model with distinct hepatic steatosis, inflammation and fibrosis, without renal pathology. ApoE(-/-) mice receiving WD represent a novel and fast model with all characteristic features of NASH and MS well suitable for NASH research. PMID- 26263023 TI - Hypothermic Machine Perfusion Decreases Renal Cell Apoptosis During Ischemia/Reperfusion Injury via the Ezrin/AKT Pathway. AB - This study aimed to explore the potential mechanisms of hypothermic machine perfusion (HMP)-a more efficient way to preserve kidneys from donors after cardiac death than static cold storage (CS), then to provide the basis for further improving donor quality. Twelve healthy male New Zealand rabbits (12 weeks old, weighing 3.0 +/- 0.3 kg) were randomly divided into two groups: the HMP group and CS group (n = 6). Rabbits' left kidney was subjected to 35 min of warm ischemic time by clamping the left renal pedicle and 1 h of reperfusion. The kidneys were then hypothermically (4-8 degrees C) preserved in vivo for 4 h with HCA-II solution using HMP or CS methods. Then rabbits underwent a right nephrectomy and the kidney tissues were collected after 24 h of reperfusion. TUNEL staining was performed on paraffin sections to detect apoptosis, and the expressions of cleaved caspase-3, ezrin, AKT, and p-AKT in frozen kidney tissues were detected by Western blotting. The ezrin expression was further confirmed by immunohistochemistry analysis. The apoptosis rate and expression of cleaved caspase-3 in the HMP group were significantly lower than the CS group (P < 0.001 and P = 0.002), meanwhile the expression of cleaved caspase-3 in the HMP and CS groups was significantly increased compared with the normal group (P = 0.035 and P < 0.001), and the expression of ezrin and p-AKT in the HMP group was significantly higher than the CS group (P = 0.005, 0.014). HMP decreased the renal cell apoptosis rate during ischemia/reperfusion injury via the ezrin/AKT pathway. PMID- 26263024 TI - N-O-Isopropyl Sulfonamido-Based Hydroxamates as Matrix Metalloproteinase Inhibitors: Hit Selection and in Vivo Antiangiogenic Activity. AB - Matrix metalloproteinases (MMPs) have been shown to be involved in tumor-induced angiogenesis. In particular, MMP-2, MMP-9, and MMP-14 have been reported to be crucial for tumor angiogenesis and the formation of metastasis, thus becoming attractive targets in cancer therapy. Here, we report our optimization effort to identify novel N-isopropoxy-arylsulfonamide hydroxamates with improved inhibitory activity toward MMP-2, MMP-9, and MMP-14 with respect to the previously discovered compound 1. A new series of hydroxamates was designed, synthesized, and tested for their antiangiogenic activity using in vitro assays with human umbilical vein endothelial cells (HUVECs). A nanomolar MMP-2, MMP-9, and MMP-14 inhibitor was identified, compound 3, able to potently inhibit angiogenesis in vitro and also in vivo in the matrigel sponge assay in mice. Finally, X-ray crystallographic and docking studies were conducted for compound 3 in order to investigate its binding mode to MMP-9 and MMP-14. PMID- 26263025 TI - Catalyst-Free Plasma Enhanced Growth of Graphene from Sustainable Sources. AB - Details of a fast and sustainable bottom-up process to grow large area high quality graphene films without the aid of any catalyst are reported in this paper. We used Melaleuca alternifolia, a volatile natural extract from tea tree plant as the precursor. The as-fabricated graphene films yielded a stable contact angle of 135 degrees , indicating their potential application in very high hydrophobic coatings. The electronic devices formed by sandwiching pentacene between graphene and aluminum films demonstrated memristive behavior, and hence, these graphene films could find use in nonvolatile memory devices also. PMID- 26263027 TI - Effects of konjac flour inclusion in gestation diets on the nutrient digestibility, lactation feed intake and reproductive performance of sows. AB - This study was conducted to investigate the effects of konjac flour (KF) inclusion in gestation diets of sows on nutrients digestibility, lactation feed intake, reproductive performance of sows and preweaning performance of piglets. Two isoenergetic and isonitrogenous gestation diets were formulated: a control diet and a 2.1% KF-supplemented diet (KF diet). Both diets had the same NDF and insoluble fiber (ISF) levels, but the KF diet had higher soluble fiber (SF) level. The day after breeding, 96 multiparous sows were assigned to the two dietary treatments. Restrict-fed during gestation, in contrast, all sows were offered the same lactation diet ad libitum. Response criteria included sow BW, backfat depth, lactation feed intake, weaning-to-estrus interval, litter size and piglet's weight at parturition and day 21 of lactation. On day 60 of gestation, 20 sows were used to measure nutrient digestibility. Results showed that the digestibility of dry matter, gross energy, crude fiber and ADF were not affected by the dietary treatments. The inclusion of KF in gestation diets increased NDF digestibility (P<0.05) and tended to increase the digestibility of CP (P=0.05) compared with the control diet group. In addition, dietary treatment during gestation did not affect litter size, BW and backfat gain during gestation, lactation weight, backfat loss or weaning-to-estrus interval of sows. However, sows fed the KF diet consumed more (P<0.05) lactation diet per day than sows in the control group. Accordingly, sows fed the KF diet showed greater average piglet weights on day 21 of lactation (P=0.09), and the litter weight of sows fed the KF diet on day 21 of lactation increased by 3.95 kg compared with sows fed the control diet (not significant). In conclusion, the inclusion of KF in gestation diets increased lactation feed intake of sows and tended to improve litter performance. PMID- 26263026 TI - Chronic Insulin Exposure Induces ER Stress and Lipid Body Accumulation in Mast Cells at the Expense of Their Secretory Degranulation Response. AB - Lipid bodies (LB) are reservoirs of precursors to inflammatory lipid mediators in immunocytes, including mast cells. LB numbers are dynamic, increasing dramatically under conditions of immunological challenge. We have previously shown in vitro that insulin-influenced lipogenic pathways induce LB biogenesis in mast cells, with their numbers attaining steatosis-like levels. Here, we demonstrate that in vivo hyperinsulinemia resulting from high fat diet is associated with LB accumulation in murine mast cells and basophils. We characterize the lipidome of purified insulin-induced LB, and the shifts in the whole cell lipid landscape in LB that are associated with their accumulation, in both model (RBL2H3) and primary mast cells. Lipidomic analysis suggests a gain of function associated with LB accumulation, in terms of elevated levels of eicosanoid precursors that translate to enhanced antigen-induced LTC4 release. Loss-of-function in terms of a suppressed degranulation response was also associated with LB accumulation, as were ER reprogramming and ER stress, analogous to observations in the obese hepatocyte and adipocyte. Taken together, these data suggest that chronic insulin elevation drives mast cell LB enrichment in vitro and in vivo, with associated effects on the cellular lipidome, ER status and pro-inflammatory responses. PMID- 26263028 TI - Acute exposure to ergot alkaloids from endophyte-infected tall fescue does not alter absorptive or barrier function of the isolated bovine ruminal epithelium. AB - Ergot alkaloids in endophyte-infected (Neotyphodium coenophialum) tall fescue (Lolium arundinaceum) have been shown to cause a reduction in blood flow to the rumen epithelium as well as a decrease in volatile fatty acids (VFA) absorption from the washed rumen of steers. Previous data also indicates that incubating an extract of endophyte-infected tall fescue seed causes an increase in the amount of VFA absorbed per unit of blood flow, which could result from an alteration in the absorptive or barrier function of the rumen epithelium. An experiment was conducted to determine the acute effects of an endophyte-infected tall fescue seed extract (EXT) on total, passive or facilitated acetate and butyrate flux across the isolated bovine rumen as well as the barrier function measured by inulin flux and tissue conductance (G t ). Flux of ergovaline across the rumen epithelium was also evaluated. Rumen tissue from the caudal dorsal sac of Holstein steers (n=6), fed a common diet, was collected and isolated shortly after slaughter and mounted between two halves of Ussing chambers. In vitro treatments included vehicle control (80% methanol, 0.5% of total volume), Low EXT (50 ng ergovaline/ml) and High EXT (250 ng ergovaline/ml). Results indicate that there is no effect of acute exposure to ergot alkaloids on total, passive or facilitated flux of acetate or butyrate across the isolate bovine rumen epithelium (P>0.51). Inulin flux (P=0.16) and G t (P>0.17) were not affected by EXT treatment, indicating no alteration in barrier function due to acute ergot alkaloid exposure. Ergovaline was detected in the serosal buffer of the High EXT treatment indicating that the flux rate is ~0.25 to 0.44 ng/cm2 per hour. Data indicate that specific pathways for VFA absorption and barrier function of the rumen epithelium are not affected by acute exposure to ergot alkaloids from tall fescue at the concentrations tested. Ergovaline has the potential to be absorbed from the rumen of cattle that could contribute to reduced blood flow and motility and lead to reduced growth rates of cattle. PMID- 26263029 TI - Effects of continuous milking during a field trial on productivity, milk protein yield and health in dairy cows. AB - The objective of this field study with an automatic milking system was to evaluate the effects of omitting the dry period on health and productivity during the subsequent lactation in dairy cows. A total of 98 German Simmental cows of six Southern German farms were assigned randomly to two experimental groups: The first group was dried-off 56 days before calving (D for dried-off, n=49), and the second group was milked continuously during this period until calving (CM for continuous milking, n=49). From the latter a third group emerged, including cows that dried-off themselves spontaneously (DS for dried-off spontaneously, n=14). Blood serum values of glucose, beta-hydroxybutyrate (BHBA), non-esterified fatty acids (NEFA) and IGF-1 showed most pronounced fluctuations in D cows. Over the entire study period, the concentrations of BHBA and NEFA were markedly lower in the CM and DS groups. Furthermore, IGF-1 concentration was lowest for D cows and also decrease in back fat thickness was more pronounced. Mean concentration of milk protein was markedly higher in CM and DS cows (3.70% and 3.71%) compared with D cows (3.38%). Owing to the lower 305-day milk yield (-15.6%) and the lower total milk yield (-3.1%), the total amount of produced protein in the subsequent lactation was 2.5% (6.8 kg) lower, although the additional protein amount in CM cows from week -8 to calving was 35.7 kg. The greatest benefit resulted from positive effects on fertility and the lower incidence of diseases: CM cows had their first oestrus 1 week earlier compared with D cows, they also conceived earlier and showed a significantly lower risk of developing hypocalcaemia, ketosis and puerperal disorders. The present study showed that the costs of medical treatment and milk losses were twice as high in D cows, compared with CM and DS cows, and thus the reduced costs because of the more stable health outweighed the financial losses of milk yield by +18.49 ? per cow and lactation. PMID- 26263030 TI - Performance and welfare of rabbit does in various caging systems. AB - The objective of the study was to compare production and welfare of rabbit does and their kits housed in various types of cages. Female rabbits were randomly allocated to four groups with the following cage types: CN: common wire-mesh flat deck cage, without footrest; CF: cage similar to the CN but with plastic footrest; ECWP: enlarged cage with wire-mesh platform; and ECPP: extra enlarged cage with plastic-mesh platform. All does were inseminated on the same day, 11 days after kindlings. Reproductive performance was evaluated during the first five consecutive kindlings. Severity of sore hocks was scored at each insemination. Location preference of the does and the platform usage of their kits were evaluated. Kindling rate, litter size (total born, born alive, alive at 21 and 35 days) and kit mortality were not significantly influenced by the cage types. The litter weight at 21 days was higher in ECWP and ECPP cages than in the CF group (3516, 3576 and 3291 g, respectively; P2.5 cm) and 3 to 4 (3=callus opened, cracks present; 4=wounds) were 58%, 60%, 78% and 48%, and 0%, 5%, 0% and 48% in groups ECPP, ECWP, CF and CN, respectively. Higher number of daily nest visits was observed for CF does than for ECWP does (12.5 v. 5.9; P2/day) was higher in the CF group than in the ECWP group (12.1 v. 3.2%; P<0.01). Within large cages, the does were observed on the platform more frequently in the ECPP cages compared with the ECWP cages (56.9% v. 31.7%; P<0.001). Similarly, 2.7% and 0.2% of kits at 21 days of age, and 33.2% and 5.2% of kits at 28 days of age, were found on the platforms of ECPP and ECWP cages, respectively. In conclusion, cages larger than the conventional ones improved kits' weaning weight, plastic footrests and plastic-mesh platforms in conventional and/or large cages reduced sore hocks' problems, plastic-mesh platforms were more used by both does and kits compared with the wire-mesh platforms. PMID- 26263031 TI - Prevalence and Determinants of Chronic Obstructive Pulmonary Disease (COPD) in Bangladesh. AB - RATIONALE: There is a paucity of population-based data on COPD prevalence and its determinants in Bangladesh. OBJECTIVE: To measure COPD prevalence and socioeconomic and lifestyle determinants among >=40 years Bangladeshi adults. METHODS: In a cross-sectional study, we measured lung function of 3744 randomly selected adults >=40 years from rural and urban areas in Bangladesh, using a handheld spirometer. COPD was defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria as post-bronchodilator ratio of Forced Expiratory Volume in 1st second (FEV1) to Forced Vital Capacity (FVC) < 0.7. In addition, COPD was also assessed by the lower limit of normal (LLN) threshold defined as lower fifth percentile for the predicted FEV1/FVC. RESULTS: The prevalence of COPD was 13.5% by GOLD criteria and 10.3% by LLN criteria. Prevalence of COPD was higher among rural than urban residents and in males than females. More than half of the COPD cases were stage II COPD by both criteria. Milder cases (Stages I and II) were over estimated by the GOLD fixed criteria, but more severe cases (Stages III and IV) were similarly classified. In multiple logistic regression analysis, older age, male sex, illiteracy, underweight, history of smoking (both current and former), history of asthma and solid fuel use were significant predictors of COPD. CONCLUSION: COPD is a highly prevalent and grossly underdiagnosed public health problem in Bangladeshi adults aged 40 years or older. Illiteracy, smoking and biomass fuel burning are modifiable determinants of COPD. PMID- 26263032 TI - Hospitalizations for COPD Exacerbations: Trends and Determinants of Death. AB - OBJECTIVES: to understand epidemiological trends in severe COPD exacerbations through analyzes of hospitalizations and deaths during three consecutive years in a French administrative region area. METHODS: Medico-administrative records of hospitalizations for COPD exacerbations were sorted from 2010 to 2012 using selected International Classification of Diseases (ICD10) codes. Four groups of hospitalization for COPD severe exacerbations were elicited leading to hospitalizations (general ward without respiratory failure, general ward with acute respiratory distress, ICU without mechanical ventilation, ICU with mechanical ventilation). RESULTS: Data extraction identified 5007, 4986 and 5359 admissions related to 4136, 4155 and 4460 patients in 2010, 2011 and 2012, respectively. Marked seasonal variations were observed. Duration of stay (median (IQR), 7 (7) vs 9 (8) vs 10 (9) vs 14 (16) days, P < .001), death rates (3.6% vs 14.2% vs 14.4% vs 21.2%, P < .01), number of co-morbid conditions (median (IQR), 2 (2) vs 2 (2) vs 4 (5) vs 4 (4.5), P < .01), type of institution (64.9% in public institution vs 79.9% vs 87.8% vs 76.6%, P < .01) were significantly associated with the hospitalization group and more than 8% of admissions led to death (3% to 24%). Age, type of institution and past hospitalizations were independent risk factors for deaths. Readmissions were infrequent but mainly related to the worsening of the co-morbid conditions. CONCLUSION: COPD severe exacerbations are frequent and lead to an important numbers of deaths related to the severity of acute respiratory failure and the number of co-morbid conditions. PMID- 26263033 TI - Walking with Non-Invasive Ventilation Does Not Prevent Exercise-Induced Hypoxaemia in Stable Hypercapnic COPD Patients. AB - BACKGROUND: Non-invasive positive pressure ventilation (NPPV) in addition to supplemental oxygen improves arterial oxygenation, walking distance and dyspnea when applied during exercise in stable hypercapnic COPD patients. The aim of the current study was to investigate whether NPPV without supplemental oxygen is capable of preventing severe exercise-induced hypoxemia in these patients when applied during walking. METHODS AND RESULTS: 15 stable hypercapnic COPD patients (FEV1 29.9 +/- 15.9%) performed two 6-minute walk tests (6MWT) with a rollator in a randomized cross-over design: using either supplemental oxygen (2.4 +/- 0.7 L/min) or NPPV (inspiratory/expiratory positive airway pressure of 28.2 +/- 2.8 / 5.5 +/- 1.5 mbar) without supplemental oxygen. RESULTS: 10 patients were able to complete both 6MWT. 6MWT with supplemental oxygen resulted in no changes for PO2 (pre: 67.3 +/- 11.2 mmHg vs. post: 65.6 +/- 12.0 mmHg, p = 0.72) whereas PCO2 increased (pre: 50.9 +/- 8.1 mmHg vs. post: 54.3 +/- 10.0 mmHg (p < 0.03). During 6MWT with NPPV PO2 significantly decreased from 66.8 +/- 7.2 mmHg to 55.5 +/- 10.6 mmHg (p < 0.02) whereas no changes occurred in PCO2 (pre: 50.6 +/- 7.5 mmHg vs. post: 53.0 +/- 7.1 mmHg; p = 0.17). Walking distance tended to be lower in 6MWT with NPPV compared to 6MWT with supplemental oxygen alone (318 +/- 160 m vs. 377 +/- 108 m; p = 0.08). CONCLUSION: The use of NPPV during walking without the application of supplemental oxygen does not prevent exercise-induced hypoxemia in patients with stable hypercapnic COPD. PMID- 26263034 TI - Emergency Admissions for COPD in an Urban Population: The Role of Population and Primary Care Factors. AB - COPD is a major cause of emergency admissions worldwide. In many countries the majority of COPD care is provided by primary care teams. This study examined variation between primary care teams in rates of COPD admission and assessed the role of prevalence, deprivation, practice performance, and general practitioner (GP) and nurse supply on risk of COPD admission. Retrospective observational study of National Health Service admissions for COPD of patients registered with London general practices over four years (2006-2009). We sought associations using negative binomial regression between COPD admissions and population factors, practice organization and practice performance. Trends in rates of COPD admissions across London were stable between 2006 and 2009. COPD admission rates varied substantially between practices (2006/7: median 13.68/10,000 population (IQR 7.83-22.70)), with almost a 3-fold difference across the interquartile range each year. Practice characteristics varied to a similar extent. Variation in practice COPD admission rates was associated with diagnosed prevalence of COPD (Rate Ratio 2.06, 95% CI 1.84-2.3) and increasing levels of deprivation (RR 1.01, 1.006-1.01). Other practice characteristics, including GP and nurse supply, and practice performance scores were not predictive of practice level COPD admission rates, when controlling for COPD prevalence and socio-economic status. Main predictors of variation in rates of COPD admissions were prevalence of diagnosed COPD and socioeconomic status. The absence of evidence that variation in primary care services for COPD was associated with rates of COPD admission emphasizes the importance of primary prevention of COPD if COPD admission rates are to fall. PMID- 26263035 TI - Trends in In-Hospital Outcomes Among Adults Hospitalized With Exacerbation of Chronic Obstructive Pulmonary Disease. AB - BACKGROUND: Although substantial advances have been made in the treatment of chronic obstructive pulmonary disease (COPD), little is known regarding the impact of these advancements on inpatient outcomes over time. We sought to examine temporal trends in in-hospital outcomes among adults hospitalized with COPD exacerbation. METHODS: The Healthcare Cost and Utilization Project's Nationwide Inpatient Sample was utilized to identify a cohort of adults hospitalized with COPD exacerbation, identified through International Classification of Diseases-9 codes. Baseline demographics, medical history, and clinical outcomes were assessed in 3,060,565 hospitalizations in patients with COPD exacerbation from 2006-2009. RESULTS: In-hospital all-cause mortality significantly decreased over the 4-year study period (5.1%, 4.7%, 4.5%, and 4.2% from 2006-2009; p < 0.001). The decline in mechanical ventilation (5.8% 5.7%, 5.3%, and 5.4% from 2006-2009; p < 0.001) was accompanied by a nearly 50% rise in noninvasive positive pressure ventilation utilization (NIPPV) (2.3%, 2.9%, 3.3%, and 3.5% from 2006-2009; p < 0.001). Average hospital length of stay (LOS) decreased over the study period (6.3, 6.1, 5.8, and 5.7 days from 2006-2009; p < 0.001). These relationships remained significant in fully-adjusted multivariate analyses (referent year 2006: p < 0.001 for years 2007-2009 for mortality, mechanical ventilation, and hospital LOS; p < 0.001 for years 2008-2009). Multivariate analysis of predictors of mortality remained similar for Years 2006 2009 with mechanical ventilation, age greater than 75 years, and NIPPV use serving as the strongest predictors of mortality. CONCLUSION: During 2006-2009, a significant decline in mortality was accompanied by less frequent mechanical ventilation, more frequent NIPPV use, and shorter LOS in adults hospitalized with COPD exacerbation. PMID- 26263036 TI - Social Support and Social Networks in COPD: A Scoping Review. AB - A scoping review was conducted to determine the size and nature of the evidence describing associations between social support and networks on health, management and clinical outcomes amongst patients with COPD. Searches of PubMed, PsychInfo and CINAHL were undertaken for the period 1966-December 2013. A descriptive synthesis of the main findings was undertaken to demonstrate where there is current evidence for associations between social support, networks and health outcomes, and where further research is needed. The search yielded 318 papers of which 287 were excluded after applying selection criteria. Two areas emerged in which there was consistent evidence of benefit of social support; namely mental health and self-efficacy. There was inconsistent evidence for a relationship between perceived social support and quality of life, physical functioning and self-rated health. Hospital readmission was not associated with level of perceived social support. Only a small number of studies (3 articles) have reported on the social network of individuals with COPD. There remains a need to identify the factors that promote and enable social support. In particular, there is a need to further understand the characteristics of social networks within the broader social structural conditions in which COPD patients live and manage their illness. PMID- 26263037 TI - Changing Pattern of Sputum Cell Counts During Successive Exacerbations of Chronic Obstructive Pulmonary Disease. AB - BACKGROUND: Chronic Obstructive Pulmonary Disease exacerbations are associated with worsening of airway inflammation, the nature of which may be neutrophilic, eosinophilic, or both. OBJECTIVE: The primary objective was to examine the cellular nature of airway inflammation in successive COPD exacerbations in order to ascertain if they changed in individual patients. The secondary objective was to estimate the relative risk indicating the extent to which a particular type of exacerbation changed as a function of the most recent exacerbation. DESIGN: This was a retrospective survey performed on a computerised sputum cell count database of a referral respiratory service in Hamilton, Canada. Recurrent event analyses were used to model the incidence of exacerbations and subtypes of exacerbations. RESULTS: 359 patients and 148 patients had sputum examined during stable condition and during exacerbations, respectively. It was found 65 patients had sputum examined during both situations. The exacerbations were eosinophilic in 15.9%, neutrophilic in 18%, combined in 2.6%, of unknown clinical significance in 19.6% and normal in 19.6%. There were missing counts for 24.3% samples. In 85.2% of patients, a different subtype of bronchitis was noted in successive exacerbations. The relative risk of a subsequent neutrophilic or eosinophilic exacerbation was 6.24 (p = 0.02) and 2.8 (p = 0.24) when the previous exacerbation was neutrophilic or eosinophilic respectively. CONCLUSIONS: This non intervention study suggests that the cellular nature of bronchitis is largely unpredictable and needs to be examined at each COPD exacerbation This has important implications in choosing the appropriate therapy. Future intervention studies would provide further evidence. PMID- 26263038 TI - Critical Factors Driving the High Volumetric Uptake of Methane in Cu3(btc)2. AB - A thorough experimental and computational study has been carried out to elucidate the mechanistic reasons for the high volumetric uptake of methane in the metal organic framework Cu3(btc)2 (btc(3-) = 1,3,5-benzenetricarboxylate; HKUST-1). Methane adsorption data measured at several temperatures for Cu3(btc)2, and its isostructural analogue Cr3(btc)2, show that there is little difference in volumetric adsorption capacity when the metal center is changed. In situ neutron powder diffraction data obtained for both materials were used to locate four CD4 adsorption sites that fill sequentially. This data unequivocally shows that primary adsorption sites around, and within, the small octahedral cage in the structure are favored over the exposed Cu(2+) or Cr(2+) cations. These results are supported by an exhaustive parallel computational study, and contradict results recently reported using a time-resolved diffraction structure envelope (TRDSE) method. Moreover, the computational study reveals that strong methane binding at the open metal sites is largely due to methane-methane interactions with adjacent molecules adsorbed at the primary sites instead of an electronic interaction with the metal center. Simulated methane adsorption isotherms for Cu3(btc)2 are shown to exhibit excellent agreement with experimental isotherms, allowing for additional simulations that show that modifications to the metal center, ligand, or even tuning the overall binding enthalpy would not improve the working capacity for methane storage over that measured for Cu3(btc)2 itself. PMID- 26263039 TI - Effects of intergenic single nucleotide polymorphisms in the fast myosin heavy chain cluster on muscle fiber characteristics and meat quality in Berkshire pigs. AB - The heterogeneity of myosin heavy chain (MyHC) isoforms is closely related to muscle fiber characteristics, and meat quality in pigs. The fast MyHC gene cluster on porcine chromosome 12 contains MYH2, MYH1, and MYH4, which encode three fast MyHC isoforms expressed in adult skeletal muscle. Here, we identified four intergenic single nucleotide polymorphisms (SNPs) in the gene cluster. Of these, SNP1 and SNP2, which were located near MYH2, were genotyped in 199 Berkshire pigs. SNP1 were significantly associated with the total fiber number (P=0.046) and intramuscular fat contents (P=0.041), and SNP2 had significant effects on type I fiber number/area compositions (P=0.039 and P=0.041, respectively), water holding capacity (drip loss, P=0.045; cooking loss, P=0.001), and meat color (P=0.003). Taken together, our results suggest that the intergenic SNPs near MYH2 can affect muscle fiber formation and meat quality by modifying the regulatory elements of this gene cluster in pigs. PMID- 26263040 TI - Low temperature, long time treatment of porcine M. longissimus thoracis et lumborum in a combi steamer under commercial conditions. AB - As the interest in low temperature, long time (LTLT) treatment of meat, as well as the use of modern combi steamer technology is growing, this study characterized the effects of LTLT treatments on porcine Musculus longissimus thoracis et lumborum in a combi steamer. Upon heating for 10 and 20 h at 53 degrees C or 58 degrees C, weight loss increased with both time and temperature, while no significant changes over time could be reached between 20 and 30 h. Redness only varied with temperature, showing lower a* values at 53 degrees C. Shear force values at 58 degrees C remained at a stable level over time and were lower than values at 53 degrees C after 10 and 20 h. In contrast, at 53 degrees C, shear force was reduced with increasing treatment time, until after 30 h both temperatures showed similar shear force values. Inoculation experiments revealed that already the lowest LTLT condition (53 degrees C, 10h) inactivated 5 log10 cfu/g of certain indicator pathogens confirming the safety of these treatments. PMID- 26263041 TI - The Development and Reliability of a Simple Field-Based Screening Tool to Assess for Scapular Dyskinesis. AB - CONTEXT: Scapular dyskinesis has been identified as a possible risk factor for injury in overhead athletes. There is a need to develop a simple, inexpensive, time-efficient field-based test that can establish the presence and severity of both scapular dyskinesis and its individual components in a musculoskeletal preparticipation screening. To ensure confidence in the test results, high reliability must be displayed. OBJECTIVE: To establish the intertester and intratester reliability of a simple field-based screening tool for scapular dyskinesis. DESIGN: Reliability study. SETTING: Athletic therapy facilities. PARTICIPANTS: 15 physically active men (19.46 +/- 0.63 y) free from any orthopedic or neurological disorders, recruited from a convenience sample of college students. INTERVENTION: Testers underwent 3 training sessions where the instructions and scoring system of the test were explained, demonstrations of the tests were given, and opportunities to practice the test were provided. Three testers independently rated 3 trials, and the process was repeated at the same time the following week. MAIN OUTCOME MEASURES: Scapular dyskinesis was assessed using the following components: winging, loss/lack of control when lifting, loss/lack of control when lowering, and scapular asymmetry. A 0-3 rating (0 = no issue, 1 = slight issue, 2 = moderate issue, 3 = severe issue) was provided by the tester independently on each side separately and on scapular asymmetry. The intraclass correlation coefficients (ICCs), 95% confidence intervals, and standard error of measurement (SEM) were computed to establish reliability. RESULTS: Excellent ICC values were found for intertester reliability (ICCs .80 1.00) and good to excellent intratester reliability (ICCs .60-1.00 for tester A, .63-1.00 for tester B, and .75-1.00 for tester C) for all components of the test. The SEM was not found to be clinically significant. CONCLUSIONS: The simple field based screening tool developed to assess scapular dyskinesis demonstrates high reliability and so is a reliable tool to use in preparticipation screenings. Future research should establish its validity. PMID- 26263042 TI - Methotrexate for maintenance of remission in ulcerative colitis. AB - BACKGROUND: Methotrexate, a folate antagonist, is an immunosuppressant drug that is effective for treating several inflammatory disorders including Crohn's disease. Ulcerative colitis, a related chronic inflammatory bowel disease, can be challenging to treat. T his updated systematic review summarizes the current evidence on the use of methotrexate for induction maintenance of remission in ulcerative colitis. OBJECTIVES: The objectives of this review were to assess the efficacy and safety of methotrexate for maintenance of remission in patients with ulcerative colitis. SEARCH METHODS: We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD/FBD group specialized trials register from inception to June 26, 2014. Study references and review papers were also searched for additional trials. Abstracts from major gastroenterological meetings were searched to identify research published in abstract form only. SELECTION CRITERIA: Randomized controlled trials in which methotrexate was compared to placebo or an active comparator in patients with quiescent ulcerative were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the risk of bias for each study. The primary outcome was the occurrence of clinical or endoscopic relapse as defined by the primary studies. Secondary outcomes included frequency and nature of adverse events, change of disease activity score and steroid-sparing effect. We calculated the risk ratio and corresponding 95% confidence interval for dichotomous outcomes. Data were analyzed on an intention-to-treat basis. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. MAIN RESULTS: Three trials (165 patients) fulfilled the inclusion criteria. One study compared oral methotrexate (12.5 mg/week) to placebo, another compared oral methotrexate (15 mg/week) to 6-mercaptopurine (6-MP, 1.5 mg/kg/day) or 5-aminosalicylic acid (5-ASA, 3 g/day) and the other compared methotrexate (15 mg/week) in combination sulfasalazine (3 g/day) to sulfasalazine. The placebo-controlled study was rated as low risk of bias. The study comparing methotrexate to 6-MP and 5-ASA was rated as high risk of bias and the study assessing methotrexate and sulfasalazine was rated as unclear risk of bias for sequence generation, allocation concealment and blinding. The placebo-controlled study found no statistically significant differences in the proportion of patients who maintained remission. At nine months, 36% (5/14) of methotrexate patients maintained remission compared to 54% (10/18) of placebo patients (RR 0.64, 95% CI 0.28 to 1.45). A GRADE analysis indicated that the overall quality of the evidence for this outcome was low due to very sparse data (15 events). The study comparing combination therapy to sulfasalazine found no statistically significant difference in the proportion of patients who maintained remission. At 12 months, 100% (14/14) of patients in the combination group maintained remission compared to 75% (9/12) of sulfasalazine patients (RR 1.32, 95% CI 0.94 to 0.86), A GRADE analysis indicated that the overall quality of the evidence for this outcome was very low due to unknown risk of bias and very sparse data (23 events). There were no statistically significant differences in maintenance of remission rates between methotrexate and 6-MP or between methotrexate and 5-ASA. At 76 weeks, 14% (1/7) of methotrexate patients maintained remission compared to 64% (7/11) of 6-MP patients (RR 0.22, 95% CI 0.03 to 1.45) and 0% (0/2) of 5-ASA patients (RR 1.13, 95% CI 0.06 to 20.71). A GRADE analysis indicated that the overall quality of the evidence from this study was very low due to high risk of bias and very sparse data. Adverse events reported in these studies included transient leucopenia, migraine, nausea and dyspepsia, mild alopecia, mild increase in aspartate aminotransferase levels, peritoneal abscess, hypoalbuminemia, severe rash and atypical pneumonia AUTHORS' CONCLUSIONS: The results for efficacy and safety outcomes between methotrexate and placebo, methotrexate and sulfasalazine, methotrexate and 6-mercaptopurine and methotrexate and 5-aminosalicylic acid were uncertain. Whether a higher dose or parenteral administration of methotrexate would be effective in quiescent ulcerative colitis is unknown. At present there is no evidence supporting the use of methotrexate for maintenance of remission in ulcerative colitis. More studies are needed to determine the efficacy and safety of methotrexate maintenance therapy in patients with quiescent ulcerative colitis. Large scale methodologically rigorous randomized controlled trials are needed. These studies should investigate higher doses of methotrexate (e.g. 15 to 25 mg/week) and parenteral administration. PMID- 26263043 TI - Clustering of CdSe/CdS Quantum Dot/Quantum Rods into Micelles Can Form Bright, Non-blinking, Stable, and Biocompatible Probes. AB - We investigate clustered CdSe/CdS quantum dots/quantum rods, ranging from single to multiple encapsulated rods within amphiphilic diblock copolymer micelles, by time-resolved optical spectroscopy. The effect of the clustering and the cluster size on the optical properties is addressed. The clusters are bright and stable and show no blinking while retaining the fundamental optical properties of the individual quantum dots/quantum rods. Cell studies show neither unspecific uptake nor morphological changes of the cells, despite the increased sizes of the clusters. PMID- 26263044 TI - Effects of stress relaxation in beta-titanium orthodontic loops: Part II. AB - OBJECTIVE: To determine which regions of beta-titanium T-loop springs (TLSs) are more affected by the stress relaxation over a 12-week period. MATERIALS AND METHODS: Fifty TLS were previously activated by concentrated bends and divided into five groups of 10 each according to their evaluation periods: immediate assessment (G0), 24 hours (G1), 48 hours (G2), 1 week (G3), and 12 weeks (G4). Groups 1 to 4 were mounted into a structure simulating a clinical situation. After the experimental periods, the springs were scanned for measurement of their angles and numbered from 1 to 9. A two-way analysis of variance was used to detect differences among the angles measured and differences caused by time and also to detect interactions between those two factors. Tukey's test was used to find differences among the groups. RESULTS: Time influenced the angulations of the TLSs (P < .001). Tukey post hoc test showed that G0 (84.1 degrees ) presented a different profile, whereas G1 (90.2 degrees ), G2 (90.7 degrees ), and G3 (91.1 degrees ) had similar profiles among each other, with G4 (92.6 degrees ) showing a mean value different from all other groups. A significant interaction was detected between activation time and angular deformation in the TLSs (P < .01). CONCLUSION: Stress relaxation was observed in the TLSs. It was greatest within 24 hours and gradually increased up to 12 weeks. Two regions were identified as responsible for the relaxation of the TLSs: one at the bend between the vertical extensions of the springs and the base arch and the other at the preactivation bends made in the base arch. PMID- 26263045 TI - Accurate DNA Assembly and Genome Engineering with Optimized Uracil Excision Cloning. AB - Simple and reliable DNA editing by uracil excision (a.k.a. USER cloning) has been described by several research groups, but the optimal design of cohesive DNA ends for multigene assembly remains elusive. Here, we use two model constructs based on expression of gfp and a four-gene pathway that produces beta-carotene to optimize assembly junctions and the uracil excision protocol. By combining uracil excision cloning with a genomic integration technology, we demonstrate that up to six DNA fragments can be assembled in a one-tube reaction for direct genome integration with high accuracy, greatly facilitating the advanced engineering of robust cell factories. PMID- 26263046 TI - "The Tools of Your Chants and Spells": Stories of Madwomen and Indian Practical Healing. AB - A longstanding trope in Indian psychiatry, and in popular representations of it, involves the efficacy of incantations and exorcism in healing afflictions of the mind, notably hysteria. In many accounts, from nineteenth century medical journals to twenty-first century popular films, a medicine deemed at once 'Western' and universal is granted the ability to diagnose neurotic afflictions, but rendered incapable of curing them, while bodily techniques referred to as 'Indian' are granted efficacy. In this article, I explore the subtleties and implications of this recurrent knowledge paradigm. I argue that a particular arrangement-one in which difference is established through equivalence-undergirds the terms by which medicine comes to be viewed as a cultural encounter. As these progressive formulations are often founded on stories about women's madness, I ask, what are the implications of an arguably pragmatic ethos founded on an uneven-and deeply gendered-resolution to postcolonial knowledge problems? PMID- 26263047 TI - Trends in pharmacological therapy following an acute coronary syndrome in Portugal: a systematic review. AB - AIMS: To assess time trends in the use of main drug classes for secondary prevention, during hospitalization and at hospital discharge, following an acute coronary syndrome, in Portugal, using a systematic review. METHODS: We searched PubMed, from inception until 2012, to identify studies reporting the proportion of acute coronary syndrome patients treated with main pharmacological therapy. We used linear regression to quantify the annual variation in use of drugs, adjusting for the proportion of men in the sample and patients' mean age, and including a quadratic term of data collection year when relevant. RESULTS: In 25 eligible studies, including patients treated from 1993 to 2009, we observed an increase in the prescription of pharmacological treatments at hospital discharge. Extrapolating from these data, and assuming a mean patient age of 65 years and 70% of men, we estimate that in 2008, 95% of patients would have been discharged with aspirin, 92% with clopidogrel, 82% with beta-blockers, 80% with angiotensin converting enzyme inhibitors and 91% with statins. Treatment during hospitalization followed a similar pattern, except for a steeper increase in angiotensin-converting enzyme inhibitors use, which was initially lower, but reached similar levels to those at discharge in recent years. CONCLUSION: In Portugal, there was an increase in the use of recommended pharmacological therapy for secondary prevention after an acute coronary syndrome over the last 15 years, during hospitalization and at hospital discharge. PMID- 26263048 TI - Hold your pauses: external globus pallidus neurons respond to behavioural events by decreasing pause activity. AB - Awareness of its rich structural pathways has earned the external segment of the globus pallidus (GPe) recognition as a central figure within the basal ganglia circuitry. Interestingly, GPe neurons are uniquely identified by the presence of prominent pauses interspersed among a high-frequency discharge rate of 50-80 spikes/s. These pauses have an average pause duration of 620 ms with a frequency of 13/min, yielding an average pause activity (probability of a GPe neuron being in a pause) of (620 * 13)/(60 * 1000) = 0.13. Spontaneous pause activity has been found to be inversely related to arousal state. The relationship of pause activity with behavioural events remains to be elucidated. In the present study, we analysed the electrophysiological activity of 200 well-isolated GPe pauser cells recorded from four non-human primates (Macaque fascicularis) while they were engaged in similar classical conditioning tasks. The isolation quality of the recorded activity and the pauses were determined with objective automatic methods. The results showed that the pause probability decreased by 9.09 and 10.0%, and the discharge rate increased by 2.96 and 1.95%, around cue and outcome presentation, respectively. Analysis of the linear relationship between the changes in pause activity and discharge rate showed r(2) = 0.46 and r(2) = 0.66 upon cue onset and outcome presentation, respectively. Thus, pause activity is a pertinent element in short-term encoding of relevant behavioural events, and has a significant, but not exclusive, role in the modulation of GPe discharge rate around these events. PMID- 26263049 TI - High Frequency of Early Repolarization and Brugada-Type Electrocardiograms in Hypercalcemia. AB - BACKGROUND: J wave, or early repolarization has recently been associated with an increased risk of lethal arrhythmia and sudden death, both in idiopathic ventricular fibrillation and in the general population. Hypercalcemia is one of the causes of J point and ST segment elevation, but the relationship has not been well studied. The aim of this study was to examine the effects of hypercalcemia on J point elevation. METHODS: Electrocardiographic findings were compared in 89 patients with hypercalcemia and 267 age- and sex-matched healthy controls with normocalcemia. The association of J point elevation with arrhythmia events in patients with hypercalcemia was also studied. RESULTS: The PR interval and the QRS duration were longer in patients with hypercalcemia than in normocalcemic controls. Both the QT and the corrected QT intervals were shorter in patients with hypercalcemia compared with normocalcemic controls. Conduction disorders, ST T abnormalities, and J point elevation were more common in patients with hypercalcemia than normocalcemic controls. Following the resolution of hypercalcemia, the frequency of J point elevation decreased to a level similar to that noted in controls. During hospitalization, no arrhythmia event occurred in patients with hypercalcemia. CONCLUSION: Hypercalcemia was associated with J point elevation. PMID- 26263050 TI - Complexation of Neptunium(V) with Glutaroimide Dioxime: A Study by Absorption Spectroscopy, Microcalorimetry, and Density Functional Theory Calculations. AB - Complexation of NpO2(+) ions with glutaroimide dioxime (H2L), a cyclic imide dioxime ligand that has been shown to form strong complexes with UO2(2+) in aqueous solutions, was studied by absorption spectroscopy and microcalorimetry in 1.0 M NaClO4 aqueous solutions. NpO2(+) forms two successive complexes, NpO2(HL)(aq) and NpO2(HL)2(-) (where HL(-) stands for the partially deprotonated glutaroimide dioxime ligand), with stability constants of log beta111 = 17.8 +/- 0.1 and log beta122 = 33.0 +/- 0.2, respectively. The complexation is both enthalpy- and entropy-driven, with negative enthalpies (DeltaH111 = -52.3 +/- 1.0 kJ/mol and DeltaH122 = -96.1 +/- 1.4 kJ/mol) and positive entropies (DeltaS111 = 164 +/- 3 J/mol/K and DeltaS122 = 310 +/- 4 J/mol/K). The thermodynamic parameters suggest that, similar to complexation of UO2(2+), the ligand coordinates with NpO2(+) in a tridentate mode, via the two oxygen atoms of the oxime groups and the nitrogen atom of the imide group. Density functional theory calculations have helped to interpret the optical absorption properties of the NpO2(HL)2(-) complex, by showing that the cis and trans configurations of the complex have very similar energies so that both configurations could be present in the aqueous solutions. It is the noncentrosymmetric cis configuration that makes the 5f -> 5f transition allowable so that the NpO2(HL)2(-) complex absorbs in the near-IR region. PMID- 26263052 TI - Molecular Dynamics Simulations of the Initial-State Predict Product Distributions of Dediazoniation of Aryldiazonium in Binary Solvents. AB - The dediazoniation of aryldiazonium salts in mixed solvents proceeds by a borderline SN1 and SN2 pathway, and product distribution should be proportional to the composition of the solvation shell of the carbon attached to the -N2 group (ipso carbon). The rates of dediazoniation of 2,4,6-trimethylbenzenediazonium in water, methanol, ethanol, propanol, and acetonitrile were similar, but measured product distributions were noticeably dependent on the nature of the water/cosolvent mixture. Here we demonstrated that solvent distribution in the first solvation shell of the ipso carbon, calculated from classical molecular dynamics simulations, is equal to the measured product distribution. Furthermore, we showed that regardless of the charge distribution of the initial state, i.e., whether the positive charge is smeared over the molecule or localized on phenyl moiety, the solvent distribution around the reaction center is nearly the same. PMID- 26263051 TI - Whole-central nervous system functional imaging in larval Drosophila. AB - Understanding how the brain works in tight concert with the rest of the central nervous system (CNS) hinges upon knowledge of coordinated activity patterns across the whole CNS. We present a method for measuring activity in an entire, non-transparent CNS with high spatiotemporal resolution. We combine a light-sheet microscope capable of simultaneous multi-view imaging at volumetric speeds 25 fold faster than the state-of-the-art, a whole-CNS imaging assay for the isolated Drosophila larval CNS and a computational framework for analysing multi-view, whole-CNS calcium imaging data. We image both brain and ventral nerve cord, covering the entire CNS at 2 or 5 Hz with two- or one-photon excitation, respectively. By mapping network activity during fictive behaviours and quantitatively comparing high-resolution whole-CNS activity maps across individuals, we predict functional connections between CNS regions and reveal neurons in the brain that identify type and temporal state of motor programs executed in the ventral nerve cord. PMID- 26263053 TI - Strategy for NMR metabolomic analysis of urine in mouse models of obesity--from sample collection to interpretation of acquired data. AB - The mouse model of monosodium glutamate induced obesity was used to examine and consequently optimize the strategy for analysis of urine samples by NMR spectroscopy. A set of nineteen easily detectable metabolites typical in obesity related studies was selected. The impact of urine collection protocol, choice of (1)H NMR pulse sequence, and finally the impact of the normalization method on the detected concentration of selected metabolites were investigated. We demonstrated the crucial effect of food intake and diurnal rhythms resulting in the choice of a 24-hour fasting collection protocol as the most convenient for tracking obesity-induced increased sensitivity to fasting. It was shown that the Carr-Purcell-Meiboom-Gill (CPMG) experiment is a better alternative to one dimensional nuclear Overhauser enhancement spectroscopy (1D-NOESY) for NMR analysis of mouse urine due to its ability to filter undesirable signals of proteins naturally present in rodent urine. Normalization to total spectral area provided comparable outcomes as did normalization to creatinine or probabilistic quotient normalization in the CPMG-based model. The optimized approach was found to be beneficial mainly for low abundant metabolites rarely monitored due to their overlap by strong protein signals. PMID- 26263054 TI - A sensitive LC-MS/MS method for the quantitative determination of biflorin in rat plasma and its application to pharmacokinetic studies. AB - A rapid, sensitive and selective liquid chromatography-tandem mass spectrometric method (LC-MS/MS) was developed for the quantification of biflorin in rat plasma. Using naringin as an internal standard, plasma samples were subjected to a direct protein precipitation process using methanol. Chromatographic separation was achieved on a Gemini C18 column with an isocratic mobile phase consisting of 0.1% formic acid and methanol (50:50, v/v) at a flow rate of 0.5mL/min. Biflorin was analyzed in the multiple reaction monitoring mode with negative electrospray ionization. The precursor/product ion pairs were m/z 353.0/205.0 and m/z 579.0/271.0 for biflorin and the IS, respectively. The calibration curve was linear over the concentration range of 5-2000ng/mL. The intra- and inter-day precision was less than 7.3% and the accuracy ranged from 96.5 to 103.3%. No significant variation was observed in the stability tests. This method was successfully applied to a pharmacokinetic study of biflorin after the intravenous and oral administration of biflorin to rats. The half-life and oral bioavailability of biflorin were determined as 3.4h and 43%, respectively. This is the first report on the quantitative determination of biflorin in rat plasma as well as the pharmacokinetic characterization of biflorin, which should provide a meaningful foundation for further preclinical and clinical applications of biflorin. PMID- 26263055 TI - Comprehensive quantification of tablets with multiple active pharmaceutical ingredients using transmission Raman spectroscopy--a proof of concept study. AB - Transmission Raman spectroscopy is a potent new tool for content uniformity testing in pharmaceutical manufacturing enabling rapid bulk sampling of a material by non-destructive means. In this proof-of-concept study, we present, for the first time, comprehensive quantification of all the constituents in a set of tablets consisting of 5 components (3 APIs and 2 excipients) by this method. The nominal concentration of individual components ranged from 1 to 85% (w/w). Two multivariate partial least-squares approaches have been used to calibrate concentration models consisting of 40 handmade tablets covering 20 sample points. These models successfully predicted all the components in a set of 10 validation tablets covering 5 different sample points. A single model for all components (PLS2) and 5 individual models each optimised for one component (PLS1) performed similarity and have been used to demonstrate that specificity of prediction has been achieved through using a multifactor orthogonal DoE for sample preparation. The ability to determine multiple analyte concentrations in one single measurement further establishes this procedure and its benefits for assay and content uniformity testing. PMID- 26263056 TI - Inhibitive activities detection of monoamine oxidases (MAO) A and B inhibitors in human liver MAO incubations by UPLC-ESI-MS/MS. AB - A sensitive UPLC-ESI-MS/MS method was developed for determining and screening of inhibitors of monoamine oxidase (MAO) by using mix MAO enzymes prepared from human liver. 5-Hydroxytryptamine (5-HT) and 2-phenethylamine (2-PEA) were used as substrates for MAO-A and MAO-B in incubations, and 5-hydroxyindole-3-acetic acid (5-HIAA) and phenylacetic acid (PAA) resulting from 5-HT and 2-PEA were used as markers to evaluate inhibitive activities of test compounds on MAO-A and MAO-B. Proper separation was achieved for positive multiple reaction monitoring of 5 HIAA (m/z 192.1->146.1) and negative multiple reaction monitoring PAA (m/z 135.0 >91.0) via isocratic elution (0.1% fromic acid:acetonitrile=60:40) on a HSS T3 column following a simple precipitation of proteins for sample treatment. The relative standard deviations of intra- and inter-day precisions were ranged from 1.74% to 6.76% and 0.77% to 9.35%. The mean accuracies for the quality control samples were 101.37+/-6.60% and 101.39+/-2.85%, respectively. This method exhibited characteristics of small total reaction volume (100MUl), short analysis time (3.5min), highly sensitivity, low cost and without matrix effect (103.56+/ 2.33% to 112.63+/-8.57% for 5-HIAA and 105.68+/-8.75% to 112.76+/-4.67% for PAA). The developed method was successfully applied for detection of the MAO-A and MAO B inhibitive activities by model drugs, including pargyline, clorgyline, as well as beta-carboline alkaloids from Peganum harmala. PMID- 26263057 TI - Proteomic analysis of beta-asarone induced cytotoxicity in human glioblastoma U251 cells. AB - Though rhizoma acori graminei (RAG) is frequently prescribed in formulations for brain tumor in traditional Chinese medicine, the potential mechanisms are still unclear. The aim of this study is to determine the effect of beta-asarone, a major component in the volatile oil of RAG, against brain tumor and elucidate the underlying molecular mechanisms. The results showed that beta-asarone significantly inhibited the cell viability of human glioblastoma U251 cells. Moreover, YO-PRO-1/PI staining revealed that cells treated with beta-asarone underwent apoptotic and necrotic death. Then, the two-dimensional gel electrophoresis (2-DE)-based proteomics was applied to investigate the different protein profiles of U251 cells treated with vehicle or beta-asarone. Sixteen proteins affected by beta-asarone were successfully identified by MALDI-TOF/TOF mass spectrometry. Gene ontology analysis showed that those proteins participated in several important biological processes and exhibited diverse molecular functions. Importantly, four proteins (heterogeneous nuclear ribonucleoprotein H1 (H), isoform CRA_b, heterogeneous nuclear ribonucleoprotein A2/B1, isoform CRA_a, ubiquitin carboxyl-terminal hydrolase isozyme L1 and cathepsin D) acting as either oncoproteins or tumor suppressors draw our special attention. Finally, the effect of beta-asarone on these four genes was confirmed at transcriptional level by semi-quantitative RT-PCR. Collectively, a variety of proteins affected by beta asarone were identified by 2-DE coupled with MALDI-TOF/TOF MS/MS analysis. Four potential protein targets were proposed, which will enable a better understanding of the anti-tumor activity of beta-asarone. PMID- 26263058 TI - An ultrasensitive LC-MS/MS method with liquid phase extraction to determine paclitaxel in both cell culture medium and lysate promising quantification of drug nanocarriers release in vitro. AB - The quantification of paclitaxel, a chemotherapy drug used to treat different types of cancers, has been performed from complete cell culture medium and cell lysate samples using a simple liquid-liquid extraction procedure in conjunction with liquid chromatography tandem mass spectrometry (LC-MS/MS). A simple sample preparation using methanol and acetic acid as a weaker acid was applied to avoid paclitaxel destruction and to achieve recovery exceeding 80 % from both matrices spiked with paclitaxel and docetaxel used as internal standard. This rapid, simple, selective and sensitive method enabled the quantification of paclitaxel within the linear range of 1-250nM in culture medium and 5-250nM in cell lysate. The lower limit of quantification was achieved in cell culture medium and cell lysates at 0.2 and 1pmol, respectively. This method was successfully applied to human non-small cell lung carcinoma cells (A549 cells) in order to quantify the amount of paclitaxel in both cell culture medium and lysate after incubation with 5, 50 and 100nM of paclitaxel. This ultra-sensitive method promises the quantification of ultra-low concentrations of paclitaxel released from any nanocarriers, allowing the determination of the kinetic profile of drug release, which is an essential parameter to validate the use of nanocarriers for drug delivery in cancer therapy. PMID- 26263059 TI - Rutaecarpine and evodiamine selected as beta1-AR inhibitor candidates using beta1 AR/CMC-offline-UPLC/MS prevent cardiac ischemia-reperfusion injury via energy modulation. AB - In the present study, an offline analytical method combining beta1-adrenergic receptor/cell membrane chromatography (beta1-AR/CMC) with ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) was used for direct recognition, separation, and identification of beta1-AR inhibitors from Evodia rutaecarpa (Juss) Benth, by which rutaecarpine and evodiamine were screened and identified as potential beta1-AR antagonists and the beta1-AR inhibition activity of them was confirmed by downregulation of cAMP and PKA in vitro test. In addition, the results of in vivo pharmacological trials revealed that rutaecarpine (1.1mg/ml) and evodiamine (1.1mg/ml) attenuated myocardial infarct size injured by myocardial ischemia/reperfusion, improved metabolism disorders between fatty acid and glucose, increased the content of ATP, Ca(2+)-ATPase activity and reduced the content of peroxisome proliferator-activated receptor alpha (PPARalpha) protein level. Thus, the beta1-AR/CMC-offline-UPLC/MS method developed in this study could be used as an effective alternative for screening beta1-AR binding bioactive components in traditional Chinese medicines and the bioactive components could be used to remedy cardiac diseases via energy modulation. PMID- 26263060 TI - Determination of arbutin and bergenin in Bergeniae Rhizoma by capillary electrophoresis with a carbon nanotube-epoxy composite electrode. AB - This report describes the fabrication and the application of a novel carbon nanotube (CNT)-epoxy composite electrode as a sensitive amperometric detector for the capillary electrophoresis (CE). The composite electrode was fabricated on the basis of the in situ polycondensation of a mixture of CNTs and 1,2-ethanediamine containing bisphenol A epoxy resin in the inner bore of a piece of fused silica capillary under heat. It was coupled with CE for the separation and detection of arbutin and bergenin in Bergeniae Rhizoma, a traditional Chinese medicine, to demonstrate its feasibility and performance. The two phenolic constituents were well separated within 10min in a 45cm capillary length at a separation voltage of 12kV using a 50mM borate buffer (pH 9.2). The CNT-based detector offered higher sensitivity, significantly lower operating potential, satisfactory resistance to surface fouling, and lower expense of operation, indicating great promise for a wide range of analytical applications. It showed long-term stability and reproducibility with relative standard deviations of less than 5% for the peak current (n=15). PMID- 26263061 TI - Preparation of a pipette tip-based molecularly imprinted solid-phase microextraction monolith by epitope approach and its application for determination of enkephalins in human cerebrospinal fluid. AB - In this study, a novel molecularly imprinted polymer (MIP) monolith for highly selective extraction of enkephalins was synthesized and prepared in a micropipette tip using epitope imprinting technique. The synthesized MIPs were characterized by scanning electron microscope (SEM) and infrared spectroscopy. A molecularly imprinted solid-phase microextraction (MISPME) method was developed for extraction of enkephalins in aqueous solutions. The parameters affecting MISPME were optimized. The results indicated that this MIP monolith exhibited specific recognition capability, high enrichment efficiency and excellent reusability for enkephalins. MALDI-TOF MS analysis demonstrated that this MIP monolith can act as a useful tool for highly selective purification and enrichment of enkephalin, a kind of low abundance protein, from high-abundance proteins in human cerebrospinal fluids (CSF). Employed this MIP monolith as solid phase microextraction column, quantitative assay of enkephalins in human CSF was developed by HPLC-ultraviolet (UV) detection in this work. The detection limits were 0.05-0.08nM. This MISPME/HPLC-UV method was used to quantify Met-enkephalin and Leu-enkephalin levels in the CSF of patients with cancer pain. PMID- 26263062 TI - Screening beta1AR inhibitors by cell membrane chromatography and offline UPLC/MS method for protecting myocardial ischemia. AB - A high expression beta1AR/cell membrane chromatography (beta1AR-CMC) and offline UPLC/MS method has been developed for screening active ingredients from Coptis chinensis. In this study, the fractions retained by CMC column were separated and identified by UPLC/MS system. Using metoprolol as a positive control drug, coptisine from C. chinensis was identified as the active component which could inhibit beta1AR. Compared with the control group: coptisine could attenuate the infarct size and release malondialdehyde (MDA) while increasing superoxide dismutase (SOD) activity, suggesting a role in reducing myocardial injury. In vitro, coptisine could decrease apoptosis, showing their protective effects upon cardiomyocytes. This beta1AR-CMC-offline-UPLC/MS method can be applied for screening active components acting on beta1AR from traditional Chinese medicines. PMID- 26263063 TI - Formation of GSH-trapped reactive metabolites in human liver microsomes, S9 fraction, HepaRG-cells, and human hepatocytes. AB - The objective was to compare several in vitro human liver-derived subcellular and cellular incubation systems for the formation of GSH-trapped reactive metabolites. Incubations of pooled human liver microsomes, human liver S9 fractions, HepaRG-cells, and human hepatocytes were performed with glutathione as a trapping agent. Experiments with liver S9 were performed under two conditions, using only NADPH and using a full set of cofactors enabling also conjugative metabolism. Ten structurally different compounds were used as a test set, chosen as either "positive" (ciprofloxacin, clozapine, diclofenac, ethinyl estradiol, pulegone, and ticlopidine) or "negative" (caffeine, citalopram, losartan, montelukast) compounds, based on their known adverse reactions on liver or bone marrow. GSH conjugates were observed for seven of the ten compounds; while no conjugates were observed for caffeine, citalopram, or ciprofloxacin. Hepatocyte and HepaRG assays produced a clearly lower number and lower relative abundance of GSH conjugates compared to assays with microsomes and S9 fractions. The major GSH conjugates were different for many compounds in cellular subfractions and cell based systems. Hepatocytes generally produced a higher number of GSH conjugates than HepaRG cells, although the differences were minor. The results show that the hepatic enzyme system used for screening of GSH-trapped reactive metabolites do have a high impact on the results, and results between different systems are comparable only qualitatively. PMID- 26263064 TI - Bayesian models of child development. AB - Bayesian models have been applied to many areas of cognitive science including vision, language, and motor learning. We discuss the implications of this framework for cognitive development. We first present a brief introduction to the Bayesian framework. Bayesian models make assumptions about representation explicit, and provide a detailed account of learning. Furthermore, they can provide an account of developmental transitions and other phenomena in development, such as curiosity and exploration. Drawing on recent work bridging empirical developmental data and modeling, we show that these features of the Bayesian approach provide solutions to problems that elude traditional accounts of learning and raise new areas of investigation. PMID- 26263065 TI - Relevance theory: pragmatics and cognition. AB - Relevance Theory is a cognitively oriented theory of pragmatics, i.e., a theory of language use. It builds on the seminal work of H.P. Grice(1) to develop a pragmatic theory which is at once philosophically sensitive and empirically plausible (in both psychological and evolutionary terms). This entry reviews the central commitments and chief contributions of Relevance Theory, including its Gricean commitment to the centrality of intention-reading and inference in communication; the cognitively grounded notion of relevance which provides the mechanism for explaining pragmatic interpretation as an intention-driven, inferential process; and several key applications of the theory (lexical pragmatics, metaphor and irony, procedural meaning). Relevance Theory is an important contribution to our understanding of the pragmatics of communication. PMID- 26263066 TI - Brain-derived neurotrophic factor Val66Met polymorphism, human memory, and synaptic neuroplasticity. AB - Some people have much better memory than others, and there is compelling evidence that a considerable proportion of this variation in memory ability is genetically inherited. A form of synaptic plasticity known as long-term potentiation (LTP) is the principal candidate mechanism underlying memory formation in neural circuits, and it might be expected, therefore, that a genetic influence on the degree of LTP might in turn influence memory abilities. Of the genetic variations thought to significantly influence mnemonic ability in humans, the most likely to have its effect via LTP is a single nucleotide polymorphism affecting brain-derived neurotrophic factor [BDNF (Val66Met)]. However, although it is likely that BDNF influences memory via a modulation of acute plasticity (i.e., LTP), BDNF also has considerable influence on structural development of neural systems. Thus, the influence of BDNF (Val66Met) on mnemonic performance via influences of brain structure as well as function must also be considered. In this brief review, we will describe the phenomenon of LTP and its study in non-human animals. We will discuss the relatively recent attempts to translate this work to studies in humans. We will describe how this has enabled investigation of the effect of the BDNF polymorphism on LTP, on brain structure, and on memory performance. PMID- 26263067 TI - Selecting and tracking multiple objects. AB - When interacting with the world, people can dynamically split attention across multiple objects in the environment, both when the objects are stationary and when the objects are moving. This type of visual processing is commonly studied in lab settings using either static selection tasks or moving tracking tasks. We describe performance limits that are common to both tasks, including limits on capacity, crowding, visual hemifield arrangement, and speed. Because these shared limits on performance suggest common underlying mechanisms, we examine a set of models that might account for limits across both. We also review cognitive neuroscience data relevant to these limits, which can provide constraints on the set of models. Finally, we examine performance limits that are unique to tracking tasks, such as trajectory encoding, and identity encoding. We argue that a complete model of multiple object tracking must account for both those limits shared between static selection and dynamic tracking, as well as limits unique to tracking. It must also provide neurally plausible mechanisms for the underlying processing resources. PMID- 26263068 TI - Food sharing and social cognition. AB - Many non-human animals share food with each other, with kin, mates, and other unrelated individuals. When individuals share food with others they lose a valuable resource. Thus, traditionally much research has investigated how this behavior can be an evolutionarily stable strategy. Only recently has food-sharing behavior been exploited to investigate non-human cognition. Certain evolutionarily stable strategies that have been proposed as accounts for food sharing behaviors, such as reciprocity and interchange, may rely on complex cognitive abilities. In these cases, individuals may calculate the benefit they may receive from sharing with the recipient. In some species, sharing of food can facilitate the recipients' rate and extent of learning. This form of teaching may be cognitively complex if the donor takes into account the level of the recipient's abilities. In addition, an animal's food-sharing behavior, which in itself may be based on a simple cognitive mechanism, could be used as a tool to investigate the extent to which the individual may be capable of complex cognitive abilities, for example, mental-state attribution. These three areas of research, reciprocity, teaching, and mental-state attribution, illustrate how food-sharing behavior can be used as a valuable natural behavior to investigate cognition in non-human animals. PMID- 26263069 TI - The perception of emotion in body expressions. AB - During communication, we perceive and express emotional information through many different channels, including facial expressions, prosody, body motion, and posture. Although historically the human body has been perceived primarily as a tool for actions, there is now increased understanding that the body is also an important medium for emotional expression. Indeed, research on emotional body language is rapidly emerging as a new field in cognitive and affective neuroscience. This article reviews how whole-body signals are processed and understood, at the behavioral and neural levels, with specific reference to their role in emotional communication. The first part of this review outlines brain regions and spectrotemporal dynamics underlying perception of isolated neutral and affective bodies, the second part details the contextual effects on body emotion recognition, and final part discusses body processing on a subconscious level. More specifically, research has shown that body expressions as compared with neutral bodies draw upon a larger network of regions responsible for action observation and preparation, emotion processing, body processing, and integrative processes. Results from neurotypical populations and masking paradigms suggest that subconscious processing of affective bodies relies on a specific subset of these regions. Moreover, recent evidence has shown that emotional information from the face, voice, and body all interact, with body motion and posture often highlighting and intensifying the emotion expressed in the face and voice. PMID- 26263070 TI - Changing tides: ecological and historical perspectives on fish cognition. AB - The capacity for specialization and radiation make fish an excellent group in which to investigate the depth and variety of animal cognition. Even though early observations of fish using tools predates the discovery of tool use in chimpanzees, fish cognition has historically been somewhat overlooked. However, a recent surge of interest is now providing a wealth of material on which to draw examples, and this has required a selective approach to choosing the research described below. Our goal is to illustrate the necessity for basing cognitive investigations on the ecological and evolutionary context of the species at hand. We also seek to illustrate the importance of ecology and the environment in honing a range of sensory systems that allow fish to glean information and support informed decision-making. The various environments and challenges with which fish interact require equally varied cognitive skills, and the solutions that fish have developed are truly impressive. Similarly, we illustrate how common ecological problems will frequently produce common cognitive solutions. Below, we focus on four topics: spatial learning and memory, avoiding predators and catching prey, communication, and innovation. These are used to illustrate how both simple and sophisticated cognitive processes underpin much of the adaptive behavioral flexibility exhibited throughout fish phylogeny. Never before has the field had such a wide array of interdisciplinary techniques available to access both cognitive and mechanistic processes underpinning fish behavior. This capacity comes at a critical time to predict and manage fish populations in an era of unprecedented global change. PMID- 26263071 TI - Analogy, higher order thinking, and education. AB - Analogical reasoning, the ability to understand phenomena as systems of structured relationships that can be aligned, compared, and mapped together, plays a fundamental role in the technology rich, increasingly globalized educational climate of the 21st century. Flexible, conceptual thinking is prioritized in this view of education, and schools are emphasizing 'higher order thinking', rather than memorization of a cannon of key topics. The lack of a cognitively grounded definition for higher order thinking, however, has led to a field of research and practice with little coherence across domains or connection to the large body of cognitive science research on thinking. We review literature on analogy and disciplinary higher order thinking to propose that relational reasoning can be productively considered the cognitive underpinning of higher order thinking. We highlight the utility of this framework for developing insights into practice through a review of mathematics, science, and history educational contexts. In these disciplines, analogy is essential to developing expert-like disciplinary knowledge in which concepts are understood to be systems of relationships that can be connected and flexibly manipulated. At the same time, analogies in education require explicit support to ensure that learners notice the relevance of relational thinking, have adequate processing resources available to mentally hold and manipulate relations, and are able to recognize both the similarities and differences when drawing analogies between systems of relationships. PMID- 26263074 TI - The Effects of Perioperative Regional Anesthesia and Analgesia on Cancer Recurrence and Survival After Oncology Surgery: A Systematic Review and Meta Analysis. AB - BACKGROUND AND OBJECTIVES: Potentially, perioperative regional anesthesia and analgesia (RA) could influence the outcomes of patients with cancer. The aim of this systematic review and meta-analysis was to evaluate the effects of perioperative RA on survival and cancer recurrence after oncologic surgery. METHODS: The authors searched computerized databases (from inception to December 2014) and reference lists and considered all studies comparing the effects of RA on cancer recurrence or overall survival with that of general anesthesia (GA). Risk estimates were pooled to determine the effects of RA on risks of cancer recurrence and mortality. Twenty eligible studies were included. RESULTS: Perioperative RA use was associated with improved overall survival (Hazard ratio [HR] = 0.84, 95% CI, 0.75 - 0.94; I =41%), but not with reduced cancer recurrence (HR=0.91, 95% CI, 0.70 - 1.18; I=83%). CONCLUSIONS: Our meta-analysis suggests that RA may improve overall survival but not reduce cancer recurrence after oncologic surgery. PMID- 26263073 TI - Binding of Multiple Rap1 Proteins Stimulates Chromosome Breakage Induction during DNA Replication. AB - Telomeres, the ends of linear eukaryotic chromosomes, have a specialized chromatin structure that provides a stable chromosomal terminus. In budding yeast Rap1 protein binds to telomeric TG repeat and negatively regulates telomere length. Here we show that binding of multiple Rap1 proteins stimulates DNA double stranded break (DSB) induction at both telomeric and non-telomeric regions. Consistent with the role of DSB induction, Rap1 stimulates nearby recombination events in a dosage-dependent manner. Rap1 recruits Rif1 and Rif2 to telomeres, but neither Rif1 nor Rif2 is required for DSB induction. Rap1-mediated DSB induction involves replication fork progression but inactivation of checkpoint kinase Mec1 does not affect DSB induction. Rap1 tethering shortens artificially elongated telomeres in parallel with telomerase inhibition, and this telomere shortening does not require homologous recombination. These results suggest that Rap1 contributes to telomere homeostasis by promoting chromosome breakage. PMID- 26263075 TI - Effects of Preoperative Serotonin-Receptor-Antagonist Administration in Spinal Anesthesia-Induced Hypotension: A Randomized, Double-blind Comparison Study of Ramosetron and Ondansetron. AB - BACKGROUND AND OBJECTIVES: The adverse effects of spinal anesthesia (SA) include arterial hypotension and bradycardia. The aim of this study was to compare the effects of 2 type 3 serotonin receptor antagonists in SA-induced adverse effects. Specifically, we assessed whether ramosetron was more effective than ondansetron in reducing SA-induced decreases in blood pressure (BP) and heart rate (HR). METHODS: A total of 117 patients undergoing orthopedic surgery and receiving SA were intravenously administered 0.3 mg of ramosetron (n = 39, group R), 4 mg of ondansetron (n = 39, group O4), or 8 mg of ondansetron (n = 39, group O8). Systolic BP (SBP), diastolic BP (DBP), mean BP (MBP), HR, and the lowest SBP, DBP, MBP, and HR values were measured preoperatively (baseline) and intraoperatively. The incidence of postoperative nausea and vomiting, the need for rescue antiemetics, the amount of patient-controlled analgesia consumption, and pain score in the first 48 hours after surgery were determined. RESULTS: Baseline values did not significantly differ among the 3 groups. After SA, SBP, DBP, MBP, and HR were lower than their baseline values in all 3 groups. The differences between the baseline and the lowest values were significantly less in group R than in groups O4 and O8 with respect to SBP (P < 0.001), DBP (P = 0.001), and MBP (P < 0.001) less in group R than in group O4 with respect to HR (P = 0.032). Intergroup differences were not significant for postoperative nausea and vomiting, the need for rescue antiemetics, patient-controlled analgesia consumption, or pain score. CONCLUSIONS: The administration of ramosetron (0.3 mg) significantly attenuated the SA-induced decrease in BP compared with 4 or 8 mg of ondansetron and HR compared with 4 mg of ondansetron. PMID- 26263076 TI - Anatomy and Pathophysiology of Spinal Cord Injury Associated With Regional Anesthesia and Pain Medicine: 2015 Update. AB - BACKGROUND AND OBJECTIVES: In March 2012, the American Society of Regional Anesthesia and Pain Medicine convened its second Practice Advisory on Neurological Complications in Regional Anesthesia and Pain Medicine. This update is based on the proceedings of that conference and relevant information published since its conclusion. This article updates previously described information on the pathophysiology of spinal cord injury and adds new material on spinal stenosis, blood pressure control during neuraxial blockade, neuraxial injury subsequent to transforaminal procedures, cauda equina syndrome/local anesthetic neurotoxicity/arachnoiditis, and performing regional anesthetic or pain medicine procedures in patients concomitantly receiving general anesthesia or deep sedation. METHODS: Recommendations are based on extensive review of research on humans or employing animal models, case reports, pathophysiology research, and expert opinion. RESULTS: The pathophysiology of spinal cord injury associated with regional anesthetic techniques is reviewed in depth, including that related to mechanical trauma from direct needle/catheter injury or mass lesions, spinal cord ischemia or vascular injury from direct needle/catheter trauma, and neurotoxicity from local anesthetics, adjuvants, or antiseptics. Specific recommendations are offered that may reduce the likelihood of spinal cord injury associated with regional anesthetic or interventional pain medicine techniques. CONCLUSIONS: The practice advisory's recommendations may, in select cases, reduce the likelihood of injury. However, many of the described injuries are neither predictable nor preventable based on our current state of knowledge. WHAT'S NEW: Since publication of initial recommendations in 2008, new information has enhanced our understanding of 5 specific entities: spinal stenosis, blood pressure control during neuraxial anesthesia, neuraxial injury subsequent to transforaminal techniques, cauda equina syndrome/local anesthetic neurotoxicity/arachnoiditis, and performing regional anesthetic or pain procedures in patients concomitantly receiving general anesthesia or deep sedation. PMID- 26263078 TI - Developing a Phonological Awareness Curriculum: Reflections on an Implementation Science Framework. AB - PURPOSE: This article describes the process of developing and implementing a supplemental early literacy curriculum designed for preschoolers demonstrating delays in literacy development. METHOD: Intervention research and implementation research have traditionally been viewed as sequential processes. This article illustrates a process of intervention development that was paralleled by a focus on implementation in early childhood settings. The exploration, preparation, implementation, sustainment framework is used to describe factors that need to be considered during a progression through these 4 phases of implementation. A post hoc analysis provides insight into a rather nonlinear progression of intervention development and highlights considerations and activities that have facilitated implementation. CONCLUSIONS: The guiding principles of the exploration, preparation, implementation, sustainment implementation science framework highlight the important considerations in developing effective and practical interventions. Considering implementation and sustainment during the intervention development process and using data-based decision making has the potential to expand the availability of user-friendly evidence-based practices in communication sciences and disorders and encourage a bridging of the researcher clinician gap. PMID- 26263077 TI - Perioperative Dexamethasone and the Development of Chronic Postmastectomy Pain: A Single-Center Observational Cohort Study. AB - BACKGROUND AND OBJECTIVES: Perioperative modulation of the surgical inflammatory response has been hypothesized as a viable pharmacological preventive target for the development of chronic pain after surgery. The objective of the current investigation was to evaluate an association between intravenous dexamethasone 4 to 20 mg on the day of surgery with self-reported pain in the breast or axilla 3 months or more after mastectomy. METHODS: The study was a secondary data analysis of a prospective cohort investigation. Subjects who have undergone mastectomy surgery were evaluated at least 3 months after the surgical procedure for the presence of chronic postsurgical pain using validated pain questionnaires. Binary logistic regression analysis was used to determine the odds of development of chronic postsurgical pain in subjects who did and did not receive perioperative dexamethasone. RESULTS: Three hundred ten patients were included in the study. Fifty-two patients (17%) met the IMMPACT (Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials) criteria for chronic pain in the breast and/or axillary region. Two hundred eleven (68%) of 310 subjects received perioperative dexamethasone on doses varying from 4 to 20 mg. The incidence of chronic pain in the mastectomy group who received perioperative dexamethasone was not different, 15 (15.2%) of 84 compared with 37 (17.5%) of 211 in the group who did not receive perioperative dexamethasone, difference -2% (95% confidence interval, -10 to 7; P = 0.75). CONCLUSIONS: Perioperative dexamethasone is not associated with a reduction in the incidence and/or severity of chronic postmastectomy pain. In addition, we did not detect a dose-response effect of dexamethasone on the incidence of chronic postsurgical pain. PMID- 26263079 TI - Laparoendoscopic single-site myomectomy compared with conventional laparoscopic myomectomy: a multicenter, randomized, controlled trial. AB - OBJECTIVE: To compare surgical outcomes of laparoendoscopic single-site myomectomy (LESS-M) vs. conventional laparoscopic myomectomy (LM). DESIGN: Multicenter, noninferiority, randomized, controlled trial. SETTING: University hospitals. PATIENT(S): A total of 100 subjects with symptomatic uterine myomas were randomly assigned to either LESS-M or conventional LM. Surgical outcomes were comparatively assessed between the groups on the basis of the intention-to treat principle. INTERVENTION(S): Laparoscopic myomectomy. MAIN OUTCOME MEASURE(S): The time required for uterine defect suturing. RESULT(S): There were no differences in baseline demographics (age, body mass index, surgical indication, number of myomas, and size and location of the largest myoma) between the two groups. The suturing time (mean +/- SD) was 21.9 +/- 10.7 minutes (95% confidence interval 18.8-24.9 min) for the LESS-M group and 23.3 +/- 12.4 minutes (95% confidence interval 19.8-26.9 min) for the conventional LM group, with no significant difference between the two groups. The other surgical outcomes, such as total operative time, operative blood loss, postoperative hemoglobin change, degree of surgical difficulty, postoperative pain scores, operative complication, and length of hospital stay, were similar between the two groups. Three subjects (6%) assigned to the LESS-M group underwent conventional LM because of difficulty in myoma enucleation and suturing, whereas no failure to intended procedure occurred in the conventional LM group (6% vs. 0). CONCLUSION(S): Laparoendoscopic single-site surgery is a feasible and safe treatment option for myomectomy that offers surgical outcomes comparable to those with conventional LM. CLINICAL TRIAL REGISTRATION NUMBER: NCT01984632. PMID- 26263080 TI - Comparison of microdissection testicular sperm extraction, conventional testicular sperm extraction, and testicular sperm aspiration for nonobstructive azoospermia: a systematic review and meta-analysis. AB - OBJECTIVE: To investigate the relative differences in outcomes among microdissection testicular sperm extraction (micro-TESE), conventional testicular sperm extraction (cTESE), and testicular sperm aspiration (TESA) in men with nonobstructive azoospermia. DESIGN: Systematic review and meta-analysis. SETTING: Outpatient academic and private urology clinics. PATIENTS(S): Men with nonobstructive azoospermia. INTERVENTION(S): Micro-TESE, cTESE, or TESA. MAIN OUTCOME MEASURE(S): Sperm retrieval (SR). RESULT(S): Fifteen studies with a total of 1,890 patients were identified. The weighted average age of the patients was 34.4 years, the follicular stimulating hormone level was 20.5 mIU/mL, the T was 373 ng/dL, and the testicular volume was 13.5 mL. In a direct comparison, performance of micro-TESE was 1.5 times more likely (95% confidence interval 1.4 1.6) to result in successful SR as compared with cTESE. Similarly, in a direct comparison, performance of cTESE was 2.0 times more likely (95% confidence interval 1.8-2.2) to result in successful SR as compared with TESA. Because of inconsistent reporting, evaluation of other procedural characteristics and pregnancy outcomes was not possible. CONCLUSION(S): Sperm retrieval was higher for micro-TESE compared with cTESE and for cTESE compared with TESA. Standardization of reported outcomes as well as combining all available SR data would help to further elucidate the SRs of these procedures. PMID- 26263081 TI - Inflammation and Cardiometabolic Risk in African American Women Is Reduced by a Pilot Community-Based Educational Intervention. AB - BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death for women, and African Americans have higher rates of CVD mortality than do other racio/ethnic groups. Women in community settings can benefit from preventive interventions, yet few investigations of successful programs have been conducted and evaluated in high-risk women, especially for metabolic syndrome. The purpose of our study was to pilot and assess the effectiveness of a 4-month pre-/post-CVD preventive educational intervention in improving knowledge, clinical risk profiles, adoption of heart-healthy lifestyles, inflammatory burden, and cardiometabolic risk in African American women in local communities. METHODS: Forty-two African American women (mean age 59 years) enrolled in the 4-month educational Cardiovascular Disease Preventive Intervention Program in Sacramento, CA, in 2010. Participants completed knowledge-based surveys pre /postintervention, provided clinical measures (weight, waist circumference, body mass index (BMI), blood pressure and blood samples for analysis of fasting glucose and lipids, and inflammatory markers: tumor necrosis factor (TNF)-alpha+/ , high-sensitivity C-reactive protein (hs-CRP), and interleukin (IL)-12. RESULTS: The CVD risk profile of participants confirmed a high-risk cohort. Postintervention (n=31), there were significant (p<0.05) gains in knowledge for all symptoms of a heart attack and calling 911; improvements in clinical risk parameters, especially for waist circumference and low-density lipoprotein (LDL) cholesterol (p<0.05); and reductions in all the inflammatory markers assessed: TNF-alpha+/-by 16%, IL-12 by 20%, and hs-CRP by 26% (p<0.05). There was also a 60% reduction in the number of participants with metabolic syndrome (MetS) (p<0.05), driven primarily by reductions in triglycerides and glucose and a rise in high-density lipoprotein (HDL) cholesterol. CONCLUSIONS: We demonstrated the efficacy of a pilot community-based educational cardiovascular program in reducing cardiometabolic risk and inflammation in high-risk African American women. Our successful culturally appropriate and sustainable model could be implemented as part of comprehensive efforts to improve community-based health outcomes. PMID- 26263082 TI - Maternal alexithymic traits, prenatal stress, and infant temperament. AB - We aimed at investigating, whether maternal alexithymia or prenatal anxiety influences infant temperament (Infant Temperament Questionnaire, IBQ) at six months. Maternal alexithymic trait of "Difficulty in Identifying Feelings" predicted higher infant "Duration of Orienting". "Fear of Bearing a Handicapped Child" predicted lower infant "Activity Level". PMID- 26263083 TI - Calculation of Electrochemical Reorganization Energies for Redox Molecules at Self-Assembled Monolayer Modified Electrodes. AB - Electrochemical electron transfer reactions play an important role in energy conversion processes with many technological applications. Electrodes modified by self-assembled monolayers (SAMs) exhibit reduced double layer effects and are used in molecular electronics. An important quantity for calculating the electron transfer rate constant is the reorganization energy, which is associated with changes in the solute geometry and the environment. In this Letter, an approach for calculating the electrochemical reorganization energy for a redox molecule attached to or near a SAM modified electrode is presented. This integral equations formalism polarizable continuum model (IEF-PCM) approach accounts for the detailed electronic structure of the molecule, as well as the contributions from the electrode, SAM, and electronic and inertial solvent responses. The calculated total reorganization energies are in good agreement with experimental data for a series of metal complexes in aqueous solution. This approach will be useful for calculating electron transfer rate constants for molecular electrocatalysts. PMID- 26263084 TI - Ultrafast Electron Transfer at Organic Semiconductor Interfaces: Importance of Molecular Orientation. AB - Much is known about the rate of photoexcited charge generation in at organic donor/acceptor (D/A) heterojunctions overaged over all relative arrangements. However, there has been very little experimental work investigating how the photoexcited electron transfer (ET) rate depends on the precise relative molecular orientation between D and A in thin solid films. This is the question that we address in this work. We find that the ET rate depends strongly on the relative molecular arrangement: The interface where the model donor compound copper phthalocyanine is oriented face-on with respect to the fullerene C60 acceptor yields a rate that is approximately 4 times faster than that of the edge on oriented interface. Our results suggest that the D/A electronic coupling is significantly enhanced in the face-on case, which agrees well with theoretical predictions, underscoring the importance of controlling the relative interfacial molecular orientation. PMID- 26263085 TI - Qualitatively Incorrect Features in the TDDFT Spectrum of Thiophene-Based Compounds. AB - Ab initio molecular electronic structure computations of thiophene-based compounds constitute an active field of research prompted by the growing interest in low-cost materials for organic electronic devices. In particular, the modeling of electronically excited states and other time-dependent phenomena has moved toward the description of more realistic albeit challenging systems. We demonstrate that due to its underlying approximations, time-dependent density functional theory predicts results that are qualitatively incorrect for thiophene and thienoacenes, although not for oligothiophene chains. The failure includes spurious state inversion and excitation characters, wrong distribution of oscillator strengths and erroneous potential energy surfaces. We briefly analyze possible origins of this behavior and identify alternative methods that alleviate these problems. PMID- 26263086 TI - Dynamic Charge Storage in Ionic Liquids-Filled Nanopores: Insight from a Computational Cyclic Voltammetry Study. AB - Understanding the dynamic charge storage in nanoporous electrodes with room temperature ionic liquid electrolytes is essential for optimizing them to achieve supercapacitors with high energy and power densities. Herein, we report coarse grained molecular dynamics simulations of the cyclic voltammetry of supercapacitors featuring subnanometer pores and model ionic liquids. We show that the cyclic charging and discharging of nanopores are governed by the interplay between the external field-driven ion transport and the sloshing dynamics of ions inside of the pore. The ion occupancy along the pore length depends strongly on the scan rate and varies cyclically during charging/discharging. Unlike that at equilibrium conditions or low scan rates, charge storage at high scan rates is dominated by counterions while the contribution by co-ions is marginal or negative. These observations help explain the perm-selective charge storage observed experimentally. We clarify the mechanisms underlying these dynamic phenomena and quantify their effects on the efficiency of the dynamic charge storage in nanopores. PMID- 26263087 TI - First-Principles Calculation of the Bulk Photovoltaic Effect in CH3NH3PbI3 and CH3NH3PbI(3-x)Cl(x). AB - Hybrid halide perovskites exhibit nearly 20% power conversion efficiency, but the origin of their high efficiency is still unknown. Here, we compute the shift current, a dominant mechanism of the bulk photovoltaic (PV) effect for ferroelectric photovoltaics, in CH3NH3PbI3 and CH3NH3PbI(3-x)Cl(x) from first principles. We find that these materials give approximately three times larger shift current PV response to near-IR and visible light than the prototypical ferroelectric photovoltaic BiFeO3. The molecular orientations of CH3NH3+ can strongly affect the corresponding PbI3 inorganic frame so as to alter the magnitude of the shift current response. Specifically, configurations with dipole moments aligned in parallel distort the inorganic PbI3 frame more significantly than configurations with near-net-zero dipole, yielding a larger shift current response. Furthermore, we explore the effect of Cl substitution on shift current and find that Cl substitution at the equatorial site induces a larger response than does substitution at the apical site. PMID- 26263088 TI - Order Parameter of the Liquid-Liquid Transition in a Molecular Liquid. AB - Liquid-liquid transitions (LLTs) between amorphous phases of a single (chemically unchanged) liquid were predicted to occur in most molecular liquids but have only been observed in triphenyl phosphite (TPP) and n-butanol, and even these examples have been dismissed as "aborted crystallization". One of the foremost reasons that LLTs remain so controversial is the lack of an obvious order parameter, that is, a physical parameter characterizing the phase transition. Here, using the technique of fluorescence lifetime imaging, we show for the first time that the LLT in TPP is characterized by a change in polarity linked to changes in molecular ordering associated with crystal polymorphs. We conclude that the LLT in TPP is a phase transition associated with frustrated molecular clusters, explaining the paucity of examples of LLTs seen in nature. PMID- 26263089 TI - Strongly Nonlinear Dependence of Energy Transfer Rate on sp(2) Carbon Content in Reduced Graphene Oxide-Quantum Dot Hybrid Structures. AB - The dependence of the energy transfer rate on the content of sp(2)-hybridized carbon atoms in the hybrid structures of reduced graphene oxide (RGO) and Mn doped quantum dot (QD(Mn)) was investigated. Taking advantage of the sensitivity of QD(Mn)'s dopant luminescence lifetime only to the energy transfer process without interference from the charge transfer process, the correlation between the sp(2) carbon content in RGO and the rate of energy transfer from QD(Mn) to RGO was obtained. The rate of energy transfer showed a strongly superlinear increase with increasing sp(2) carbon content in RGO, suggesting the possible cooperative behavior of sp(2) carbon domains in the energy transfer process as the sp(2) carbon content increases. PMID- 26263090 TI - Optical Description of Mesostructured Organic-Inorganic Halide Perovskite Solar Cells. AB - Herein we describe both theoretically and experimentally the optical response of solution-processed organic-inorganic halide perovskite solar cells based on mesostructured scaffolds. We develop a rigorous theoretical model using a method based on the propagation of waves in layered media, which allows visualizing the way in which light is spatially distributed across the device and serves to quantify the fraction of light absorbed by each medium comprising the cell. The discrimination between productive and parasitic absorption yields an accurate determination of the internal quantum efficiency. State-of-the-art devices integrating mesoporous scaffolds infiltrated with perovskite are manufactured and characterized to support the calculations. This combined experimental and theoretical analysis provides a rational understanding of the optical behavior of perovskite cells and can be beneficial for the judicious design of devices with improved performance. Notably, our model justifies the presence of a solid perovskite capping layer in all of the highest efficiency perovskite solar cells based on thinner mesoporous scaffolds. PMID- 26263091 TI - Temporally Anticorrelated Motion of Nanoparticles at a Liquid Interface. AB - Quantum dots at the hexane-glycerol interface exhibited unexpected behavior including highly dynamic adsorption/desorption, where the lateral nanoparticle motion was anomalously fast immediately after adsorption and prior to desorption. At the interface, particles exhibited pseudo-Brownian lateral motion, in which the instantaneous diffusion coefficient was temporally anticorrelated, in agreement with our simulations involving fractional Brownian motion in the surface-normal direction. These phenomena suggest that, in contrast to the conventional picture for colloidal particles, nanoparticles explore a landscape of metastable interfacial positions, with different exposures to the two adjacent phases. PMID- 26263092 TI - Coupled Oscillations and Circadian Rhythms in Molecular Replication Networks. AB - Living organisms often display rhythmic and oscillatory behavior. We investigate here a challenge in contemporary Systems Chemistry, that is, to construct "bottom up" molecular networks that display such complex behavior. We first describe oscillations during self-replication by applying kinetic parameters relevant to peptide replication in an open environment. Small networks of coupled oscillators are then constructed in silico, producing various functions such as logic gates, integrators, counters, triggers, and detectors. These networks are finally utilized to simulate the connectivity and network topology of the Kai proteins circadian clocks from the S. elongatus cyanobacteria, thus producing rhythms whose constant frequency is independent of the input intake rate and robust toward concentration fluctuations. We suggest that this study helps further reveal the underlying principles of biological clocks and may provide clues into their emergence in early molecular evolution. PMID- 26263093 TI - Complex Refractive Index Spectra of CH3NH3PbI3 Perovskite Thin Films Determined by Spectroscopic Ellipsometry and Spectrophotometry. AB - The complex refractive index (dielectric function) of planar CH3NH3PbI3 thin films at room temperature is investigated by variable angle spectroscopic ellipsometry and spectrophotometry. Knowledge of the complex refractive index is essential for designing photonic devices based on CH3NH3PbI3 thin films such as solar cells, light-emitting diodes, or lasers. Because the directly measured quantities (reflectance, transmittance, and ellipsometric spectra) are inherently affected by multiple reflections, the complex refractive index has to be determined indirectly by fitting a model dielectric function to the experimental spectra. We model the dielectric function according to the Forouhi-Bloomer formulation with oscillators positioned at 1.597, 2.418, and 3.392 eV and achieve excellent agreement with the experimental spectra. Our results agree well with previously reported data of the absorption coefficient and are consistent with Kramers-Kronig transformations. The real part of the refractive index assumes a value of 2.611 at 633 nm, implying that CH3NH3PbI3-based solar cells are ideally suited for the top cell in monolithic silicon-based tandem solar cells. PMID- 26263094 TI - Nonadiabatic Quantum Dynamics Predissociation of H2O(+)(B (2)B2). AB - A quantum-mechanical study of the predissociation of H2O(+) (B (2)B2) is carried out by using wave packet propagations on ab initio potential energy surfaces connected by nonadiabatic couplings. The simulations show that within the first 30 fs 80% of the initial wave packet is transferred from the B (2)B2 to the A (2)A1 electronic state through a conical intersection. A much slower transfer (in the ps time scale) from the A (2)A1 to the X (2)B1 state due to a Renner-Teller coupling determines the fragmentation branching ratios, which are in accordance with the experimental measurements. PMID- 26263095 TI - The Next Breakthrough for Organic Photovoltaics? AB - While the intense focus on energy level tuning in organic photovoltaic materials has afforded large gains in device performance, we argue here that strategies based on microstructural/morphological control are at least as promising in any rational design strategy. In this work, a meta-analysis of ~150 bulk heterojunction devices fabricated with different materials combinations is performed and reveals strong correlations between power conversion efficiency and morphology-dominated properties (short-circuit current, fill factor) and surprisingly weak correlations between efficiency and energy level positioning (open-circuit voltage, enthalpic offset at the interface, optical gap). While energy level positioning should in principle provide the theoretical maximum efficiency, the optimization landscape that must be navigated to reach this maximum is unforgiving. Thus, research aimed at developing understanding-based strategies for more efficient optimization of an active layer microstructure and morphology are likely to be at least as fruitful. PMID- 26263096 TI - Quantum-Dot-Based Solar Cells: Recent Advances, Strategies, and Challenges. AB - Among next-generation photovoltaic systems requiring low cost and high efficiency, quantum dot (QD)-based solar cells stand out as a very promising candidate because of the unique and versatile characteristics of QDs. The past decade has already seen rapid conceptual and technological advances on various aspects of QD solar cells, and diverse opportunities, which QDs can offer, predict that there is still ample room for further development and breakthroughs. In this Perspective, we first review the attractive advantages of QDs, such as size-tunable band gaps and multiple exciton generation (MEG), beneficial to solar cell applications. We then analyze major strategies, which have been extensively explored and have largely contributed to the most recent and significant achievements in QD solar cells. Finally, their high potential and challenges are discussed. In particular, QD solar cells are considered to hold immense potential to overcome the theoretical efficiency limit of 31% for single-junction cells. PMID- 26263097 TI - Long-Range Electron Transfer in Engineered Azurins Exhibits Marcus Inverted Region Behavior. AB - The Marcus theory of electron transfer (ET) predicts that while the ET rate constants increase with rising driving force until it equals a reaction's reorganization energy, at higher driving force the ET rate decreases, having reached the Marcus inverted region. While experimental evidence of the inverted region has been reported for organic and inorganic ET reactions as well as for proteins conjugated with ancillary redox moieties, evidence of the inverted region in a "protein-only" system has remained elusive. We herein provide such evidence in a series of nonderivatized proteins. These results may facilitate the design of ET centers for future applications such as advanced energy conversions. PMID- 26263098 TI - How Much N-Doping Can Graphene Sustain? AB - Doped, substituted, or alloyed graphene is an attractive candidate for use as a tunable element of future nanomechanical and optoelectronic devices. Here we use the density functional theory, density functional tight binding, cluster expansion, and molecular dynamics to investigate the thermal stability and electronic properties of a binary 2D alloy of graphitic carbon and nitrogen (C(1 x)N(x)). The stability range naturally begins from graphene and must end before x = 1, where pure nitrogen rather forms molecular gas. This poses a compelling question of what highest x < 1 still permits stable 2D hexagonal lattice. Such upper limit on the nitrogen concentration that is achievable in a stable alloy can be found based on the phonon and molecular dynamics calculations. The stability switchover is predicted to between x = 1/3 (33.3%) and x = 3/8 (37.5%), and no stable hexagonal lattice two-dimensional CN alloys can exist at the N concentration of x = 3/8 (37.5%) and higher. PMID- 26263099 TI - Overcoming Coulombic Traps: Geometry and Electronic Characterizations of Light Induced Separated Spins at the Bulk Heterojunction Interface. AB - Recent progress is overviewed on experimental elucidations of fundamental molecular functions of the light-energy conversions by the photoactive layers of the organic photovoltalic (OPV) cells by means of the time-resolved electron paramagnetic resonance spectroscopy. Positions and orientations of the unpaired electrons and electronic coupling matrix elements are clarified in photoinduced, primary charge-separated (CS) states. Connections between the molecular geometries and the electronic couplings have been characterized for the initial CS states to elucidate how the structure, orbital delocalization, and molecular libration play roles on exothermic carrier dissociation via a vibrationally relaxed charge-transfer complex with prevention of the energy-wasting charge recombination. Superior functions to biological molecules are presented for the efficient photocurrent generations induced by orbital delocalization and by shallow trap depths at polymer-stacking domains. The above structural and electronic characteristics of the primary electron-hole pairs are essential to evaluations, designs, and developments of the efficient solar cells using organic molecules. PMID- 26263100 TI - Bend Excitation Is Predicted to Greatly Accelerate Isomerization of trans Hydroxymethylene to Formaldehyde in the Deep Tunneling Region. AB - Using a new potential energy surface, based on fitting around 33,000 CCSD(T) F12/aug-cc-pVTZ energies, a robust set of predictions is made for mode-specific isomerization of trans-hydroxymethylene to formaldehyde in the deep tunneling region. The calculations make use of a recent projection model for mode-specific tunneling based on the rectilinear Q(im) path [ Wang , Y. ; Bowman , J. M. J. Chem. Phys. 2013 , 139 , 154303 ]. The most interesting prediction is a large decrease in the half-life from roughly 5 h for the ground vibrational state to roughly 1.5 min and 1 s by excitation of the fundamental and first overtone of the asymmetric bending normal mode, respectively. The properties of the new PES are described along with variational calculations of low-lying vibrational states of trans- and cis-hydroxymethylene. PMID- 26263101 TI - Efficient, Semitransparent Neutral-Colored Solar Cells Based on Microstructured Formamidinium Lead Trihalide Perovskite. AB - Efficient, neutral-colored semitransparent solar cells are of commercial interest for incorporation into the windows and surfaces of buildings and automobiles. Here, we report on semitransparent perovskite solar cells that are both efficient and neutral-colored, even in full working devices. Using the microstructured architecture previously developed, we achieve higher efficiencies by replacing methylammonium lead iodide perovskite with formamidinium lead iodide. Current voltage hysteresis is also much reduced. Furthermore, we apply a novel transparent cathode to the devices, enabling us to fabricate neutral-colored semitransparent full solar cells for the first time. Such devices demonstrate over 5% power conversion efficiency for average visible transparencies of almost 30%, retaining impressive color-neutrality. This makes these devices the best performing single-junction neutral-colored semitransparent solar cells to date. These microstructured perovskite solar cells are shown to have a significant advantage over silicon solar cells in terms of performance at high incident angles of sunlight, making them ideal for building integration. PMID- 26263102 TI - Photocatalytic Activity of Inorganic Semiconductor Surfaces: Myths, Hype, and Reality. PMID- 26263103 TI - Interrogating the Carbon and Oxygen K-Edge NEXAFS of a CO2-Dosed Hyperbranched Aminosilica. AB - Using near-edge X-ray absorption fine structure (NEXAFS) spectroscopy, we shed light on the nature of the interaction between CO2 and the amine moieties in a hyperbranched aminosilica (HAS) material, a porous aminosilica composite with great potential for postcombustion carbon capture applications. We show that after dosing a pristine (annealed) HAS sample with CO2, the C K-edge NEXAFS spectrum presents a new pi* resonance at 289.9 eV, which can be attributed to the formation of a C?O (carbonyl) bond. Additional analyses of the O K-edge using model samples containing carbamate, carbonate, and bicarbonate functional groups as reference demonstrate a carbamate bonding mechanism for the chemical adsorption of CO2 by the HAS material under the conditions employed. These findings show the capability of the C and O K-edge NEXAFS technique to identify CO2-adsorbate species despite the high concentration of C and O atoms inherently present in the sample (prior to CO2 dosing) and the significant similarities between the possible adsorbates. PMID- 26263104 TI - Effect of Carrier Thermalization Dynamics on Light Emission and Amplification in Organometal Halide Perovskites. AB - The remarkable rise of organometal halide perovskites as solar photovoltaic materials has been followed by promising developments in light-emitting devices, including lasers. Here we present unique insights into the processes leading to photon emission in these materials. We employ ultrafast broadband photoluminescence (PL) and transient absorption spectroscopies to directly link density dependent ultrafast charge dynamics to PL. We find that exceptionally strong PL at the band edge is preceded by thermalization of free charge carriers. Short-lived PL above the band gap is clear evidence of nonexcitonic emission from hot carriers, and ultrafast PL depolarization confirms that uncorrelated charge pairs are precursors to photon emission. Carrier thermalization has a profound effect on amplified stimulated emission at high fluence; the delayed onset of optical gain we resolve within the first 10 ps and the unusual oscillatory behavior are both consequences of the kinetic interplay between carrier thermalization and optical gain. PMID- 26263105 TI - Are Room-Temperature Ionic Liquids Dilute Electrolytes? AB - An important question in understanding the structure of ionic liquids is whether ions are truly "free" and mobile, which would correspond to a concentrated ionic melt, or are rather "bound" in ion pairs, that is, a liquid of ion pairs with a small concentration of free ions. Recent surface force balance experiments from different groups have given conflicting answers to this question. We propose a simple model for the thermodynamics and kinetics of ion pairing in ionic liquids. Our model takes into account screened ion-ion, dipole-dipole, and dipole-ion interactions in the mean-field limit. The results of this model suggest that almost two-thirds of the ions are free at any instant, and ion pairs have a short lifetime comparable to the characteristic time scale for diffusion. These results suggest that there is no particular thermodynamic or kinetic preference for ions to reside in pairs. We therefore conclude that ionic liquids are concentrated, rather than dilute, electrolytes. PMID- 26263106 TI - Emergence of Hysteresis and Transient Ferroelectric Response in Organo-Lead Halide Perovskite Solar Cells. AB - Although there has been rapid progress in the efficiency of perovskite-based solar cells, hysteresis in the current-voltage performance is not yet completely understood. Owing to its complex structure, it is not easy to attribute the hysteretic behavior to any one of different components, such as the bulk of the perovskite or different heterojunction interfaces. Among organo-lead halide perovskites, methylammonium lead iodide perovskite (CH3NH3PbI3) is known to have a ferroelectric property. The present investigation reveals a strong correlation between transient ferroelectric polarization of CH3NH3PbI3 induced by an external bias in the dark and hysteresis enhancement in photovoltaic characteristics. Our results demonstrate that the reverse bias poling (-0.3 to -1.1 V) of CH3NH3PbI3 photovoltaic layers prior to the photocurrent-voltage measurement generates stronger hysteresis whose extent changes significantly by the cell architecture. The phenomenon is interpreted as the effect of remanent polarization in the perovskite film on the photocurrent, which is most enhanced in planar perovskite structures without mesoporous scaffolds. PMID- 26263107 TI - Modeling the Self-Aggregation of Small AOT Reverse Micelles from First Principles. AB - This Letter is the first attempt at studying the self-aggregation of AOT reverse micelles from first-principles. It focuses on predicting the aggregation number, the radius of gyration, and the hydrodynamic radius of a low water content reverse micelle by theoretical means. We show that molecular dynamics simulation in the MUs time range combined with atomistic potentials is capable of reproducing and explaining, to a convenient degree, experimental results on the size and dimensions of reverse micelles of AOT of low water content, [H2O]/[AOT] ~ 5. PMID- 26263108 TI - Al-Air Batteries: Fundamental Thermodynamic Limitations from First-Principles Theory. AB - The Al-air battery possesses high theoretical specific energy (4140 W h/kg) and is therefore an attractive candidate for vehicle propulsion. However, the experimentally observed open-circuit potential is much lower than what bulk thermodynamics predicts, and this potential loss is typically attributed to corrosion. Similarly, large Tafel slopes associated with the battery are assumed to be due to film formation. We present a detailed thermodynamic study of the Al air battery using density functional theory. The results suggest that the maximum open-circuit potential of the Al anode is only -1.87 V versus the standard hydrogen electrode at pH 14.6 instead of the traditionally assumed -2.34 V and that large Tafel slopes are inherent in the electrochemistry. These deviations from the bulk thermodynamics are intrinsic to the electrochemical surface processes that define Al anodic dissolution. This has contributions from both asymmetry in multielectron transfers and, more importantly, a large chemical stabilization inherent to the formation of bulk Al(OH)3 from surface intermediates. These are fundamental limitations that cannot be improved even if corrosion and film effects are completely suppressed. PMID- 26263110 TI - Sum over Histories Representation for Chemical Kinetics. AB - A new representation for chemical kinetics is introduced that is based on a sum over histories formulation that employs chemical pathways defined at a molecular level. The time evolution of a chemically reactive system is described by enumerating the most important pathways followed by a chemical moiety. An explicit formula for the pathway probabilities is derived and takes the form of an integral over a time-ordered product. When evaluating long pathways, the time ordered product has a simple Monte Carlo representation that is computationally efficient. A small numerical stochastic simulation was used to identify the most important paths to include in the representation. The method was applied to a realistic H2/O2 combustion problem and is shown to yield accurate results. PMID- 26263111 TI - Time-Resolved Photodetachment Anisotropy: Gas-Phase Rotational and Vibrational Dynamics of the Fluorescein Anion. AB - The photoelectron signal of the singly deprotonated fluorescein anion is found to be highly dependent on the relative polarization between pump and probe pulses, and time-resolved photodetachment anisotropy (TR-PA) is developed as a probe of the rotational dynamics of the chromophore. The total photoelectron signal shows both rotational and vibrational wavepacket dynamics, and we demonstrate how TR-PA can readily disentangle these dynamical processes. TR-PA in fluorescein presents specific opportunities for its development as a probe for rotational dynamics in large biomolecules as fluorescein derivatives are commonly incorporated in complex biomolecules and have been used extensively in time-resolved fluorescence anisotropy measurements, to which TR-PA is a gas-phase analogue. PMID- 26263112 TI - Correction to "Mosaic of Water Orientation Structures at a Neutral Zwitterionic Lipid/Water Interface Revealed by Molecular Dynamics Simulations". PMID- 26263113 TI - Molecular Structure and Chirality Detection by Fourier Transform Microwave Spectroscopy. AB - We describe a three-wave mixing experiment using time-separated microwave pulses to detect the enantiomer-specific emission signal of the chiral molecule using Fourier transform microwave (FTMW) spectroscopy. A chirped-pulse FTMW spectrometer operating in the 2-8 GHz frequency range is used to determine the heavy-atom substitution structure of solketal (2,2-dimethyl-1,3-dioxolan-4-yl methanol) through analysis of the singly substituted (13)C and (18)O isotopologue rotational spectra in natural abundance. A second set of microwave horn antennas is added to the instrument design to permit three-wave mixing experiments where an enantiomer-specific phase of the signal is observed. Using samples of R-, S-, and racemic solketal, the properties of the three-wave mixing experiment are presented, including the measurement of the corresponding nutation curves to demonstrate the optimal pulse sequence. PMID- 26263114 TI - A Comparison of Charge Separation Dynamics in Organic Blend Films Employing Fullerene and Perylene Diimide Electron Acceptors. AB - We report a comparison of charge carrier dynamics and device performance for low band gap polymer PBDTTT-CT in blends with the fullerene acceptor PC71BM and a PDI derivative with similar electron affinities. Charge separation and recombination dynamics are found to be remarkably similar for these two acceptors, with both blends exhibiting efficient, ultrafast charge separation (time constants of 1.6 and 1.4 ps, respectively). The lower device performance for the PDI acceptor (1.75% compared to 3.5% for the equivalent PC71BM device) is shown to result from slower charge transport, increasing nongeminate recombination losses during charge collection. PMID- 26263115 TI - Supramolecular Interactions in Secondary Plant Cell Walls: Effect of Lignin Chemical Composition Revealed with the Molecular Theory of Solvation. AB - Plant biomass recalcitrance, a major obstacle to achieving sustainable production of second generation biofuels, arises mainly from the amorphous cell-wall matrix containing lignin and hemicellulose assembled into a complex supramolecular network that coats the cellulose fibrils. We employed the statistical-mechanical, 3D reference interaction site model with the Kovalenko-Hirata closure approximation (or 3D-RISM-KH molecular theory of solvation) to reveal the supramolecular interactions in this network and provide molecular-level insight into the effective lignin-lignin and lignin-hemicellulose thermodynamic interactions. We found that such interactions are hydrophobic and entropy-driven, and arise from the expelling of water from the mutual interaction surfaces. The molecular origin of these interactions is carbohydrate-pi and pi-pi stacking forces, whose strengths are dependent on the lignin chemical composition. Methoxy substituents in the phenyl groups of lignin promote substantial entropic stabilization of the ligno-hemicellulosic matrix. Our results provide a detailed molecular view of the fundamental interactions within the secondary plant cell walls that lead to recalcitrance. PMID- 26263116 TI - Boosting the Photovoltage of Dye-Sensitized Solar Cells with Thiolated Gold Nanoclusters. AB - Glutathione-capped gold nanoclusters (Aux-GSH NCs) are anchored along with a sensitizing squaraine dye on a TiO2 surface to evaluate the cosensitizing role of Au(x)-GSH NCs in dye-sensitized solar cells (DSSCs). Photoelectrochemical measurements show an increase in the photoconversion efficiency of DSSCs when both sensitizers are present. The observed photoelectrochemical improvements in cosensitized DSSCs are more than additive effects as evident from the increase in photovoltage (DeltaV as high as 0.24 V) when Au(x)-GSH NCs are present. Electron equilibration and accumulation within gold nanoclusters increase the quasi-Fermi level of TiO2 closer to the conduction band and thus decrease the photovoltage penalty. A similar beneficial role of gold nanoclusters toward boosting the V(oc) and enhancing the efficiency of Ru(II) polypyridyl complex-sensitized solar cells is also discussed. PMID- 26263117 TI - Cobalt(III)-Catalyzed C2-Selective C-H Alkynylation of Indoles. AB - A cobalt(III)-catalyzed C-2 selective C-H alkynylation of indoles using hypervalent iodine-alkyne reagents is described. A broad range of synthetically useful functional groups (-F, -Cl, -Br, -CO2Me, -CN) were tolerated, providing an efficient and robust protocol for the synthesis of C-2 alkynylated indoles. The pyrimidyl and silyl protecting groups could be easily removed to give the corresponding 2-ethynyl-1H-indole. PMID- 26263120 TI - Breakthrough pain in cancer patients: prevalence, mechanisms and treatment options. AB - PURPOSE OF REVIEW: The aim of this article was to examine the definition, the characteristics, and the management of breakthrough cancer pain (BTP) in cancer patients by a critical review of recent literature. RECENT FINDINGS: BTP should be more correctly defined as an episode of severe intensity in patients receiving an adequate treatment with opioids able to provide at least mild analgesia. BTP is a heterogeneous condition as episodes vary between individuals. BTP can be classified into two big distinct pictures: spontaneous-type and incident-type pain. The principal pharmacological treatment of BTP is represented by the administration of opioids as needed. Recent reviews revealed that transmucosal preparation of fentanyl provided superior and more rapid pain relief as compared with placebo in the first 30 min after dosing. Few comparison studies among fentanyl products have been performed.Finally, although dose titration was recommended for years, a meaningful dosing according to the level of opioid tolerance may enhance the advantages of such products. SUMMARY: BTP represents a serious problem reported by many cancer patients despite receiving regular use of opioids. Subgroups of breakthrough pain have been identified. Different modalities of pharmacological interventions are available. Further studies are warranted to assess the net benefit of these drugs to assist decision-making by patients, clinicians, and payers according to individual clinical conditions. PMID- 26263121 TI - Awake craniotomy: improving the patient's experience. AB - PURPOSE OF REVIEW: Awake craniotomy patients are exposed to various stressful stimuli while their attention and vigilance is important for the success of the surgery. We describe several recent findings on the perception of awake craniotomy patients and address nonpharmacological perioperative factors that enhance the experience of awake craniotomy patients. These factors could also be applicable to other surgical patients. RECENT FINDINGS: Proper preoperative counseling gives higher patient satisfaction and should be individually tailored to the patient. Furthermore, there is a substantial proportion of patients who have significant pain or fear during an awake craniotomy procedure. There is a possibility that this could induce post-traumatic stress disorder or related symptoms. SUMMARY: Preoperative preparation is of utmost importance in awake craniotomy patients, and a solid doctor-patient relationship is an important condition. Nonpharmacological intraoperative management should focus on reduction of fear and pain by adaptation of the environment and careful and well considered communication. PMID- 26263122 TI - Neuropathic pain assessment: update on laboratory diagnostic tools. AB - PURPOSE OF REVIEW: The purpose of this review was to provide an update on the diagnostic tools for neuropathic pain for clinical practice. RECENT FINDINGS: The new definition of neuropathic pain by the International Association for the Study of Pain requires confirmation of a lesion or disease affecting the somatosensory system. In addition to traditional diagnostic procedures, for example, nerve conduction studies, skin biopsies depict morphological alteration and/or rarefication of the small intraepidermal nerve fibers and were recently used to identify small fiber abnormalities, for example, in patients with fibromyalgia or sarcoidosis. Quantitative sensory testing assesses the somatosensory function including both peripheral and central pathways. A recent consensus statement discussed its diagnostic value. Corneal confocal microscopy is a noninvasive method enabling in-vivo assessment of the small nerve fibers in the cornea and also seems to identify patients at risk for developing diabetic neuropathy at an early stage and to reflect the improvement of neuropathy after treatment. Further promising methods are the microneurography and nociceptive evoked potentials; however, they are technically challenging and their diagnostic value for clinical practice has yet to be confirmed. SUMMARY: For diagnosing neuropathic pain, confirmation of a lesion or disease affecting the somatosensory system is needed. Better clinical phenotyping will hopefully enable individualized mechanism-based treatment of neuropathic pain. PMID- 26263123 TI - Postoperative care of the neurosurgical patient. AB - PURPOSE OF REVIEW: Monitoring and therapy of patients in neurocritical care are areas of intensive research and the current evidence needs further confirmation. RECENT FINDINGS: A consensus statement of the Neurocritical Care Society and the European Society of Intensive Care Medicine provided pragmatic guidance and recommendations for multimodal monitoring in neurocritical care patients. Only a minority of these recommendations have strong evidence. In addition, recent multicenter randomized controlled trials concerning the therapy of subarachnoidal hemorrhage and traumatic brain injury could not show decreased mortality or improved functional neurologic outcome after the interventions. The current evidence for monitoring and medical therapy in patients after traumatic brain injury and aneurysmal subarachnoid hemorrhage is highlighted in this review. SUMMARY: Although strong evidence is lacking, multimodal monitoring is of great value in neurocritical care patients and may help to provide patients with the optimal therapy based on the individual pathophysiological changes. PMID- 26263124 TI - Tuning the Thermoelectric Properties of a Conducting Polymer through Blending with Open-Shell Molecular Dopants. AB - Polymer thermoelectric devices are emerging as promising platforms by which to convert thermal gradients into electricity directly, and poly(3,4-ethylene dioxythiophene) doped with poly(styrenesulfonate) ( PEDOT: PSS) is a leading candidate in a number of these thermoelectric modules. Here, we implement the stable radical-bearing small molecule 4-hydroxy-2,2,6,6-tetramethylpiperidin-1 oxyl (TEMPO-OH) as an intermolecular dopant in order to tune the electrical conductivity, thermopower, and power factor of PEDOT: PSS thin films. Specifically, we demonstrate that, at moderate loadings (~2%, by weight) of the open-shell TEMPO-OH molecule, the thermopower of PEDOT: PSS thin films is increased without a marked decline in the electrical conductivity of the material. This effect, in turn, allows for an optimization of the power factor in the composite organic materials, which is a factor of 2 greater than the pristine PEDOT: PSS thin films. Furthermore, because the loading of TEMPO-OH is relatively low, we observe that there is little change in either the crystalline nature or surface topography of the composite films relative to the pristine PEDOT: PSS films. Instead, we determine that the increase in the thermopower is due to the presence of stable radical sites within the PEDOT: PSS that persist despite the highly acidic environment that occurs due to the presence of the poly(styrenesulfonate) moiety. Additionally, the oxidation-reduction-active (redox-active) nature of the TEMPO-OH small molecules provides a means by which to filter charges of different energy values. Therefore, these results demonstrate that a synergistic combination of an open-shell species and a conjugated polymer allows for enhanced thermoelectric properties in macromolecular systems, and as such, it offers the promise of a new design pathway in polymer thermoelectric materials. PMID- 26263125 TI - Binding Kinetics versus Affinities in BRD4 Inhibition. AB - Bromodomains (BRDs) are protein modules that selectively recognize histones as a "reader" by binding to an acetylated lysine substrate. The human BRD4 has emerged as a promising drug target for a number of disease pathways, and several potent BRD inhibitors have been discovered experimentally recently. However, the detailed inhibition mechanism especially for the inhibitor binding kinetics is not clear. Herein, by employing classical molecular dynamics (MD) and state-of the-art density functional QM/MM MD simulations, the dynamic characteristics of ZA-loop in BRD4 are revealed. And then the correlation between binding pocket size and ZA-loop motion is elucidated. Moreover, our simulations found that the compound (-)-JQ1 could be accommodated reasonably in thermodynamics whereas it is infeasible in binding kinetics against BRD4. Its racemate (+)-JQ1 proved to be both thermodynamically reasonable and kinetically achievable against BRD4, which could explain the previous experimental results that (+)-JQ1 shows a high inhibitory effect toward BRD4 (IC50 is 77 nM) while (-)-JQ1 is inactive (>10 MUM). Furthermore, the L92/L94/Y97 in the ZA-loop and Asn140 in the BC-loop are identified to be critical residues in (+)-JQ1 binding/releasing kinetics. All these findings shed light on further selective inhibitor design toward BRD family, by exploiting the non-negligible ligand binding kinetics features and flexible ZA-loop motions of BRD, instead of only the static ligand-protein binding affinity. PMID- 26263126 TI - Charge-Transfer Effects in Ligand Exchange Reactions of Au25 Monolayer-Protected Clusters. AB - Reported here are second-order rate constants of associative ligand exchanges of Au25L18 nanoparticles (L = phenylethanethiolate) of various charge states, measured by proton nuclear magnetic resonance at room temperature and below. Differences in second-order rate constants (M(-1) s(-1)) of ligand exchange (positive clusters ~1.9 * 10(-5) versus negative ones ~1.2 * 10(-4)) show that electron depletion retards ligand exchange. The ordering of rate constants between the ligands benzeneselenol > 4-bromobenzene thiol > benzenethiol reveals that exchange is accelerated by higher acidity and/or electron donation capability of the incoming ligand. Together, these observations indicate that partial charge transfer occurs between the nanoparticle and ligand during the exchange and that this is a rate-determining effect in the process. PMID- 26263127 TI - Quantifying the Extent of Contact Doping at the Interface between High Work Function Electrical Contacts and Poly(3-hexylthiophene) (P3HT). AB - We demonstrate new approaches to the characterization of oxidized regioregular poly(3-hexylthiophene-2,5-diyl) (P3HT) that results from electronic equilibration with device-relevant high work function electrical contacts using high-resolution X-ray (XPS) and ultraviolet (UPS) photoelectron spectroscopy (PES). Careful interpretation of photoemission signals from thiophene sulfur atoms in thin (ca. 20 nm or less) P3HT films provides the ability to uniquely elucidate the products of charge transfer between the polymer and the electrical contact, which is a result of Fermi-level equilibration between the two materials. By comparing high resolution S 2p core-level spectra to electrochemically oxidized P3HT standards, the extent of the contact doping reaction is quantified, where one in every six thiophene units (ca. 20%) in the first monolayer is oxidized. Finally, angle resolved XPS of both pure P3HT and its blends with phenyl-C61-butyric acid methyl ester (PCBM) confirms that oxidized P3HT species exist near contacts with work functions greater than ca. 4 eV, providing a means to characterize the interface and "bulk" region of the organic semiconductor in a single film. PMID- 26263129 TI - Intramolecular Charge Transfer in 4-Aminobenzonitrile Does Not Need the Twist and May Not Need the Bend. AB - A study combining accurate quantum chemistry and full-dimensional quantum dynamics is presented to confirm the existence of an ultrafast radiationless decay channel from the charge-transfer state to the locally excited state in 4 aminobenzonitrile. This intramolecular charge-transfer pathway proceeds through a newly found planar conical intersection, and it is shown to be more efficient in the presence of acetonitrile than in the gas phase. Our results are consistent with recent experimental observations. PMID- 26263128 TI - Characterization of Parallel beta-Sheets at Interfaces by Chiral Sum Frequency Generation Spectroscopy. AB - Characterization of protein secondary structures at interfaces is still challenging due to the limitations of surface-selective optical techniques. Here, we address the challenge of characterizing parallel beta-sheets by combining chiral sum frequency generation (SFG) spectroscopy and computational modeling. We focus on human islet amyloid polypeptide aggregates and a de novo designed short polypeptide at lipid/water and air/glass interfaces. We find that parallel beta sheets adopt distinct orientations at various interfaces and exhibit characteristic chiroptical responses in the amide I and N-H stretch regions. Theoretical analysis indicates that the characteristic chiroptical responses provide valuable information on the symmetry, orientation, and vibrational couplings of parallel beta-sheet at interfaces. PMID- 26263130 TI - Temporal Fluctuations in Excimer-Like Interactions between pi-Conjugated Chromophores. AB - Inter- or intramolecular coupling processes between chromophores such as excimer formation or H- and J-aggregation are crucial to describing the photophysics of closely packed films of conjugated polymers. Such coupling is highly distance dependent and should be sensitive to both fluctuations in the spacing between chromophores as well as the actual position on the chromophore where the exciton localizes. Single-molecule spectroscopy reveals these intrinsic fluctuations in well-defined bichromophoric model systems of cofacial oligomers. Signatures of interchromophoric interactions in the excited state--spectral red shifting and broadening and a slowing of photoluminescence decay--correlate with each other but scatter strongly between single molecules, implying an extraordinary distribution in coupling strengths. Furthermore, these excimer-like spectral fingerprints vary with time, revealing intrinsic dynamics in the coupling strength within one single dimer molecule, which constitutes the starting point for describing a molecular solid. Such spectral sensitivity to sub-Angstrom molecular dynamics could prove complementary to conventional FRET-based molecular rulers. PMID- 26263131 TI - Fast Dissociation and Reduced Auger Recombination of Multiple Excitons in Closely Packed PbS Nanocrystal Thin Films. AB - Exciton decay dynamics in chemically treated PbS quantum-dot (QD) films have been studied using femtosecond transient-absorption (TA) spectroscopy. In photoconductive QD films, a decay component with a lifetime of a few nanoseconds appeared in the TA signals because of exciton dissociation under weak excitation. Increasing excitation fluence resulted in additional fast-decay components corresponding to the lifetimes of multiple excitons, which decreased with increasing photoconductivity of the closely packed QD films. Auger recombination in photoexcited QDs was suppressed in highly photoconductive films. Our findings clearly show that the carrier transfer between the QDs dominates the lifetimes of single and multiple excitons. PMID- 26263132 TI - Origin of Dirac Cones in SiC Silagraphene: A Combined Density Functional and Tight-Binding Study. AB - The formation of Dirac cones in electronic band structures via isomorphous transformation is demonstrated in 2D planar SiC sheets. Our combined density functional and tight-binding calculations show that 2D SiC featuring C-C and Si Si atom pairs possesses Dirac cones (DCs), whereas an alternative arrangement of C and Si leads to a finite band gap. The origin of Dirac points is attributed to bare interactions between Si-Si bonding states (valence bands, VBs) and C-C antibonding states (conduction bands, CBs), while the VB-CB coupling opens up band gaps elsewhere. A mechanism of atom pair coupling is proposed, and the conditions required for DC formation are discussed, enabling one to design a class of 2D binary Dirac fermion systems on the basis of DF calculations solely for pure and alternative binary structures. PMID- 26263133 TI - Substance Release Triggered by Biomolecular Signals in Bioelectronic Systems. AB - A new approach to bioelectronic Sense-and-Act systems was developed with the use of modified electrodes performing sensing and substance-releasing functions. The sensing electrode was activated by biomolecular/biological signals ranging from small biomolecules to proteins and bacterial cells. The activated sensing electrode generated reductive potential and current, which stimulated dissolution of an Fe(3+)-cross-linked alginate matrix on the second connected electrode resulting in the release of loaded biochemical species with different functionalities. Drug-mimicking species, antibacterial drugs, and enzymes activating a biofuel cell were released and tested for various biomedical and biotechnological applications. The studied systems offer great versatility for future applications in controlled drug release and personalized medicine. Their future applications in implantable devices with autonomous operation are proposed. PMID- 26263134 TI - Controlling Catalytic Selectivity via Adsorbate Orientation on the Surface: From Furfural Deoxygenation to Reactions of Epoxides. AB - Specificity to desired reaction products is the key challenge in designing solid catalysts for reactions involving addition or removal of oxygen to/from organic reactants. This challenge is especially acute for reactions involving multifunctional compounds such as biomass-derived aromatic molecules (e.g., furfural) and functional epoxides (e.g., 1-epoxy-3-butene). Recent surface-level studies have shown that there is a relationship between adsorbate surface orientation and reaction selectivity in the hydrogenation pathways of aromatic oxygenates and the ring-opening or ring-closing pathways of epoxides. Control of the orientation of reaction intermediates on catalytic surfaces by modifying the surface or near-surface environment has been shown to be a promising method of affecting catalytic selectivity for reactions of multifunctional molecules. In this Perspective, we review recent model studies aimed at understanding the surface chemistry for these reactions and studies that utilize this insight to rationally design supported catalysts. PMID- 26263135 TI - Role of LiCoO2 Surface Terminations in Oxygen Reduction and Evolution Kinetics. AB - Oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) activities of LiCoO2 nanorods with sizes in the range from 9 to 40 nm were studied in alkaline solution. The sides of these nanorods were terminated with low-index surfaces such as (003), while the tips were terminated largely with high-index surfaces such as (104), as revealed by high-resolution transmission electron microscopy. Electron energy loss spectroscopy demonstrated that low-spin Co(3+) prevailed on the sides, while the tips exhibited predominantly high- or intermediate-spin Co(3+). We correlated the electronic and atomic structure to higher specific ORR and OER activities at the tips as compared to the sides, which was accompanied by more facile redox of Co(2+/3+) and higher charge transferred per unit area. These findings highlight the critical role of surface terminations and electronic structures of transition-metal oxides on the ORR and OER activity. PMID- 26263136 TI - Probing the Ultrafast Energy Dissipation Mechanism of the Sunscreen Oxybenzone after UVA Irradiation. AB - Oxybenzone is a common constituent of many commercially available sunscreens providing photoprotection from ultraviolet light incident on the skin. Femtosecond transient electronic and vibrational absorption spectroscopies have been used to investigate the nonradiative relaxation pathways of oxybenzone in cyclohexane and methanol after excitation in the UVA region. The present data suggest that the photoprotective properties of oxybenzone can be understood in terms of an initial ultrafast excited state enol -> keto tautomerization, followed by efficient internal conversion and subsequent vibrational relaxation to the ground state (enol) tautomer. PMID- 26263137 TI - Molecular Orientation Analysis of Alkyl Methylene Groups from Quantitative Coherent Anti-Stokes Raman Scattering Spectroscopy. AB - Quantitative data analysis in coherent anti-Stokes Raman scattering (CARS) spectroscopy is important for extracting molecular structural information. We developed a method to derive molecular tilt angle with respect to the surface normal based on quantitative CARS spectral analysis. We showed that the tilt angle of methylene alkyl chains on a surface can be directly obtained from the CH2 symmetric/asymmetric peak ratio in a CARS spectrum. The lipid alkyl chain tilt angle from a lipid monolayer was measured to be ~0 degrees and was verified by sum frequency generation spectroscopy, which probes the orientations of the lipid methyl end groups. The tilt angle of a silane monolayer alkyl chain was derived to be ~35 degrees , which agrees with the theoretical prediction. This method is submonolayer sensitive and can also be used to interpret polarization dependent signals in CARS microscopy. It can be applied to elucidate detailed molecular structure from CARS spectroscopic and microscopic measurements. PMID- 26263138 TI - High Yield Ultrafast Intramolecular Singlet Exciton Fission in a Quinoidal Bithiophene. AB - We report the process of singlet exciton fission with high-yield upon photoexcitation of a quinoidal thiophene molecule. Efficient ultrafast triplet photogeneration and its yield are determined by photoinduced triplet-triplet absorption, flash photolysis triplet lifetime measurements, as well as by femtosecond time-resolved transient absorption and fluorescence methods. These experiments show that optically excited quinoidal bithiophene molecule undergoes ultrafast formation of the triplet-like state with the lifetime ~57 MUs. CASPT2 and RAS-SF calculations have been performed to support the experimental findings. To date, high singlet fission rates have been reported for crystalline and polycrystalline materials, whereas for covalently linked dimers and small oligomers it was found to be relatively small. In this contribution, we show an unprecedented quantum yield of intramolecular singlet exciton fission of ~180% for a quinoidal bithiophene system. PMID- 26263140 TI - New Structure Model of Au22(SR)18: Bitetrahederon Golden Kernel Enclosed by [Au6(SR)6] Au(I) Complex. AB - The study of atomic structure of thiolate-protected gold with decreased core size is important to explore the structural evolution from Au(I) complex to Au nanoclusters. In this work, we theoretically predicted the structure of recently synthesized four valence electron (4e) Au22(SR)18 cluster. The Au22(SR)18 cluster is proposed to possess a bitetrahedron Au7 kernel that is surrounded by a unique [Au6(SR)6] Au(I) complex and three Au3(SR)4 staple motifs. More interestingly, the Au22(SR)18 exhibits structural connections with Au24(SR)20 and Au20(SR)16. The stability of Au22(SR)18 can be understood from the superatom electronic configuration of the Au kernel as well as the formation of superatomic network. The present study can offer new insight into the structural evolution as well as electronic structure of thiolate-protected Au nanoclusters. PMID- 26263139 TI - Critical Assessment of the Strength of Hydrogen Bonds between the Sulfur Atom of Methionine/Cysteine and Backbone Amides in Proteins. AB - Gas-phase vibrational spectroscopy, coupled cluster (CCSD(T)), and dispersion corrected density functional (B97-D3) methods are employed to characterize surprisingly strong sulfur center H-bonded (SCHB) complexes between cis and trans amide NH and S atom of methionine and cysteine side chain. The amide N-H...S H bonds are compared with the representative classical sigma- and pi-type H-bonded complexes such as N-H...O, N-H...O?C and N-H...pi H-bonds. With the spectroscopic, theoretical, and structural evidence, amide N-H...S H-bonds are found to be as strong as the classical sigma-type H-bonds, despite the smaller electronegativity of sulfur in comparison to oxygen. The strength of backbone amide N-H...S H-bonds in cysteine and methionine containing peptides and proteins are also investigated and found to be of similar magnitudes as those observed in the intermolecular model complexes studied in this work. All such SCHBs also confirm that the electronegativities of the acceptors are not the sole criteria to predict the H-bond strength. PMID- 26263141 TI - Interfacial Charge Transfer Anisotropy in Polycrystalline Lead Iodide Perovskite Films. AB - Solar cells based on organic-inorganic lead iodide perovskite (CH3NH3PbI3) exhibit remarkably high power conversion efficiency (PCE). One of the key issues in solution-processed films is that often the polycrystalline domain orientation is not well-defined, which makes it difficult to predict energy alignment and charge transfer efficiency. Here we combine ab initio calculations and photoelectron spectroscopy to unravel the electronic structure and charge redistribution at the interface between different surfaces of CH3NH3PbI3 and typical organic hole acceptor Spiro-OMeTAD and electron acceptor PCBM. We find that both hole and electron interfacial transfer depend strongly on the CH3NH3PbI3 surface orientation: while the (001) and (110) surfaces tend to favor hole injection to Spiro-OMeTAD, the (100) surface facilitates electron transfer to PCBM due to surface delocalized charges and hole/electron accumulation at the CH3NH3PbI3/organic interfaces. Molecular dynamic simulations indicate that this is due to strong orbital interactions under thermal fluctuations at room temperature, suggesting the possibility to further improve charge separation and extraction in perovskite-based solar cells by controlling perovskite film crystallization and surface orientation. PMID- 26263142 TI - Position-Dependent Three-Dimensional Diffusion in Nematic Liquid Crystal Monitored by Single-Particle Fluorescence Localization and Tracking. AB - Anisotropic mass diffusion in liquid crystals (LCs) is important from the point of both basic LC physics and their applications in optoelectronic devices. We use super-resolution fluorescence microscopy with astigmatic imaging to track 3D diffusion of quantum dots (QDs) in an ordered nematic LC. The method allowed us to evaluate the diffusion coefficients independently along the three spatial axes as well as to determine the absolute position of the QD with respect to the cell wall. We found variations of the diffusion coefficient along the different directions across the cell thickness and explained these as being due to changes of a tilt angle of the LC director. Close to the surface, the diffusion is slowed down due to the confinement effect of the cell wall. Overall, the QD diffusion is much slower than expected for a corresponding particle size. This phenomenon is suggested to originate from reorientation of the LC director in the vicinity of the particle. PMID- 26263143 TI - Polarization Switching and Light-Enhanced Piezoelectricity in Lead Halide Perovskites. AB - We investigate the ferroelectric properties of photovoltaic methylammonium lead halide CH3NH3PbI3 perovskite using piezoelectric force microscopy (PFM) and macroscopic polarization methods. The electric polarization is clearly observed by amplitude and phase hysteresis loops. However, the polarization loop decreases as the frequency is lowered, persisting for a short time only, in the one second regime, indicating that CH3NH3PbI3 does not exhibit permanent polarization at room temperature. This result is confirmed by macroscopic polarization measurement based on a standard capacitive method. We have observed a strong increase of piezoelectric response under illumination, consistent with the previously reported giant photoinduced dielectric constant at low frequencies. We speculate that an intrinsic charge transfer photoinduced dipole in the perovskite cage may lie at the origin of this effect. PMID- 26263144 TI - Close Packing of Nitroxide Radicals in Stable Organic Radical Polymeric Materials. AB - The relationship between the polymer network and electronic transport properties for stable radical polymeric materials has come under investigation owing to their potential application in electronic devices. For the radical polymer poly(2,2,6,6-tetramethylpiperidine-4-yl-1-oxyl methacrylate), it is unclear whether the radical packing is optimal for charge transport partially because the relationship between radical packing and molecular structure is not well understood. Using the paramagnetic nitroxide radical as a probe of the polymer and synthetic techniques to control the radical concentration on the methyl methacrylate backbone, we investigate the dependence of radical concentration on molecular structure. The electron paramagnetic resonance data indicate that radicals in the PTMA assume a closest approach distance to each other when more than 60% of the backbone is populated with radical pendant groups. Below 60% coverage, the polymer rearranges to accommodate larger radical-radical spacing. These findings are consistent with theoretical calculations and help explain some experimentally determined electron-transport properties. PMID- 26263145 TI - Photons, Physical Chemistry, and the Year of Light--A Virtual Issue. PMID- 26263146 TI - Photoinduced Energy Shift in Quantum-Dot-Sensitized TiO2: A First-Principles Analysis. AB - We investigate the photoinduced dipole (PID) phenomenon, which holds enormous potential for the optimization of quantum dot-sensitized solar cells (QDSSCs), by means of first-principles electronic structure calculations. We demonstrate that the sensitization of the TiO2 substrate with core/shell QDs produces almost no changes in the ground state but decisively improves the performance upon photoexcitation. In particular, the maximum attainable VOC is predicted to increase by ~25 meV due to two additive effects: (i) the displacement of the photoexcited hole away from the TiO2 surface and (ii) the interfacial electrostatic interaction established between the TiO2-injected electrons and the holes residing in the QD core. We believe that this work, explaining the mechanisms by which PID cells deliver better efficiencies, paves the way for the design of new QDSSCs with improved efficiencies. PMID- 26263147 TI - Reactivity of Fluorographene: A Facile Way toward Graphene Derivatives. AB - Fluorographene (FG) is a two-dimensional graphene derivative with promising application potential; however, its reactivity is not understood. We have systematically explored its reactivity in vacuum and polar environments. The C-F bond dissociation energies for homo- and heterolytic cleavage are above 100 kcal/mol, but the barrier of SN2 substitution is significantly lower. For example, the experimentally determined activation barrier of the FG reaction with NaOH in acetone equals 14 +/- 5 kcal/mol. The considerable reactivity of FG indicates that it is a viable precursor for the synthesis of graphene derivatives and cannot be regarded as a chemical counterpart of Teflon. PMID- 26263148 TI - Highly Active Epitaxial La(1-x)Sr(x)MnO3 Surfaces for the Oxygen Reduction Reaction: Role of Charge Transfer. AB - Most studies of oxide catalysts for the oxygen reduction reaction (ORR) use oxide powder, where the heterogeneity of exposed surfaces and the composite nature of electrodes limit fundamental understanding of the reaction mechanism. We present the ORR activity of epitaxially oriented La(1-x)Sr(x)MnO3 surfaces and investigate, by varying Sr substitution, the relationship between the role of charge transfer and catalytic activity in an alkaline environment. The activity is greatest for La(1-x)Sr(x)MnO3 with 33% Sr, containing mixed Mn(3+/4+), and the (110) and (111) orientations display comparable activities to that of the (001). Electrochemical measurements using the facile redox couple [Fe(CN)6](3-/4-) illustrate that increasing ORR activity trends with faster charge-transfer kinetics, indicating the importance of facile charge transfer at the oxide/water interface and mixed Mn valence in promoting ORR kinetics. PMID- 26263149 TI - Sucralose Destabilization of Protein Structure. AB - Sucralose is a commonly employed artificial sweetener that behaves very differently than its natural disaccharide counterpart, sucrose, in terms of its interaction with biomolecules. The presence of sucralose in solution is found to destabilize the native structure of two model protein systems: the globular protein bovine serum albumin and an enzyme staphylococcal nuclease. The melting temperature of these proteins decreases as a linear function of sucralose concentration. We correlate this destabilization to the increased polarity of the molecule. The strongly polar nature is manifested as a large dielectric friction exerted on the excited-state rotational diffusion of tryptophan using time resolved fluorescence anisotropy. Tryptophan exhibits rotational diffusion proportional to the measured bulk viscosity for sucrose solutions over a wide range of concentrations, consistent with a Stokes-Einstein model. For sucralose solutions, however, the diffusion is dependent on the concentration, strongly diverging from the viscosity predictions, and results in heterogeneous rotational diffusion. PMID- 26263150 TI - Insights into Laccase Engineering from Molecular Simulations: Toward a Binding Focused Strategy. AB - Understanding the molecular determinants of enzyme performance is of primary importance for the rational design of ad hoc mutants. A novel approach, which combines efficient conformational sampling and quick reactivity scoring, is used here to shed light on how substrate oxidation was improved during the directed evolution experiment of a fungal laccase (from Pycnoporus cinnabarinus), an industrially relevant class of oxidoreductases. It is found that the enhanced activity of the evolved enzyme is mainly the result of substrate arrangement in the active site, with no important change in the redox potential of the T1 copper. Mutations at the active site shift the binding mode into a more buried substrate position and provide a more favorable electrostatic environment for substrate oxidation. As a consequence, engineering the binding event seems to be a viable way to in silico evolution of oxidoreductases. PMID- 26263151 TI - Grain Structures and Boundaries on Microcrystalline Copper Covered with an Octadecanethiol Monolayer Revealed by Sum Frequency Generation Microscopy. AB - An octadecanethiol (ODT) self-assembled monolayer on microcrystalline copper was investigated by sum frequency generation (SFG) imaging microscopy. The crystal grain and grain boundaries of the copper surface were mapped in the SFG image based on the strong brightness contrast of the SFG signal across the boundary. Local SFG spectra reveal significant difference with each other as well as the average SFG spectra, indicating the heterogeneity of the copper surface resulting from copper grains with distinct crystallographic facets and orientations. It is demonstrated that the SFG signal of crystalline domain areas contains azimuthal anisotropy with respect to the plane of incidence. In addition, the statistical orientation analyses of amplitude ratio of CH3-sym/CH3-asym and corresponding contour maps imply that the orientation of ODT molecules is affected by the underlying copper. PMID- 26263152 TI - Density Functional Calculations of Native Defects in CH3NH3PbI3: Effects of Spin Orbit Coupling and Self-Interaction Error. AB - Native point defects play an important role in carrier transport properties of CH3NH3PbI3. However, the nature of many important defects remains controversial due partly to the conflicting results reported by recent density functional theory (DFT) calculations. In this Letter, we show that self-interaction error and the neglect of spin-orbit coupling (SOC) in many previous DFT calculations resulted in incorrect positions of valence and conduction band edges, although their difference, which is the band gap, is in good agreement with the experimental value. This problem has led to incorrect predictions of defect-level positions. Hybrid density functional calculations, which partially correct the self-interaction error and include the SOC, show that, among native point defects (including vacancies, interstitials, and antisites), only the iodine vacancy and its complexes induce deep electron and hole trapping levels inside of the band gap, acting as nonradiative recombination centers. PMID- 26263153 TI - Electron-Driven Proton Transfer Along H2O Wires Enables Photorelaxation of pisigma* States in Chromophore-Water Clusters. AB - The fates of photochemically formed pisigma* states are one of the central issues in photobiology due to their significant contribution to the photostability of biological matter, formation of hydrated electrons, and the phenomenon of photoacidity. Nevertheless, our understanding of the underlying molecular mechanisms in aqueous solution is still incomplete. In this paper, we report on the results of nonadiabatic photodynamics simulations of microhydrated 2 aminooxazole molecule employing algebraic diagrammatic construction to the second order. Our results indicate that electron-driven proton transfer along H2O wires induces the formation of pisigma*/S0 state crossing and provides an effective deactivation channel. Because we recently have identified a similar channel for 4 aminoimidazole-5-carbonitrile [Szabla, R.; Phys. Chem. Chem. Phys. 2014, 16, 17617-17626 ], we conclude this mechanism may be quite common to all heterocyclic compounds with low-lying pisigma* states. PMID- 26263154 TI - Determination of Spin Inversion Probability, H-Tunneling Correction, and Regioselectivity in the Two-State Reactivity of Nonheme Iron(IV)-Oxo Complexes. AB - We show by experiments that nonheme Fe(IV)O species react with cyclohexene to yield selective hydrogen atom transfer (HAT) reactions with virtually no C?C epoxidation. Straightforward DFT calculations reveal, however, that C?C epoxidation on the S = 2 state possesses a low-energy barrier and should contribute substantially to the oxidation of cyclohexene by the nonheme Fe(IV)O species. By modeling the selectivity of this two-site reactivity, we show that an interplay of tunneling and spin inversion probability (SIP) reverses the apparent barriers and prefers exclusive S = 1 HAT over mixed HAT and C?C epoxidation on S = 2. The model enables us to derive a SIP value by combining experimental and theoretical results. PMID- 26263155 TI - Harnessing Excited-State Intramolecular Proton-Transfer Reaction via a Series of Amino-Type Hydrogen-Bonding Molecules. AB - A series of new amino (NH)-type hydrogen-bonding (H-bonding) compounds comprising 2-(2'-aminophenyl)benzothiazole and its extensive derivatives were designed and synthesized. Unlike in the hydroxyl (OH)-type H-bonding systems, one of the amino hydrogens can be replaced with electron-donating/withdrawing groups. This, together with a versatile capability for modifying the parent moiety, makes feasible the comprehensive spectroscopy and dynamics studies of amino-type excited-state intramolecular proton transfer (ESIPT), which was previously inaccessible in the hydroxyl-type ESIPT systems. Empirical correlations were observed among the hydrogen-bonding strength (the N-H bond distances and proton acidity), ESIPT kinetics, and thermodynamics, demonstrating a trend that the stronger N-H...N hydrogen bond leads to a faster ESIPT, as experimentally observed, and a more exergonic reaction thermodynamics. Accordingly, ESIPT reaction can be harnessed for the first time from a highly endergonic type (i.e., prohibition) toward equilibrium with a measurable ESIPT rate and then to the highly exergonic, ultrafast ESIPT reaction within the same series of amino-type intramolecular H-bond system. PMID- 26263156 TI - Angle-Resolved Photoemission of Solvated Electrons in Sodium-Doped Clusters. AB - Angle-resolved photoelectron spectroscopy of the unpaired electron in sodium doped water, methanol, ammonia, and dimethyl ether clusters is presented. The experimental observations and the complementary calculations are consistent with surface electrons for the cluster size range studied. Evidence against internally solvated electrons is provided by the photoelectron angular distribution. The trends in the ionization energies seem to be mainly determined by the degree of hydrogen bonding in the solvent and the solvation of the ion core. The onset ionization energies of water and methanol clusters do not level off at small cluster sizes but decrease slightly with increasing cluster size. PMID- 26263157 TI - Phase Dependence of Double-Resonance Experiments in Rotational Spectroscopy. AB - We here report on double-resonance experiments using broadband chirped pulse Fourier transform microwave spectroscopy that can facilitate spectral assignment and yield information about weak transitions with high resolution and sensitivity. Using the diastereomers menthone and isomenthone, we investigate the dependence of pumping a radio frequency transition on both the amplitude and phase of the signal from a microwave transition with which it shares a common rotational level. We observe a strong phase change when scanning the radio frequency through molecular resonance. The direction of the phase change depends on the energy level arrangement, that is, if it is progressive or regressive. The experimental results can be simulated using the three-level optical Bloch equations and described with the AC Stark effect, giving rise to an Autler-Townes splitting. PMID- 26263158 TI - Thermoplasmonic ssDNA Dynamic Release from Gold Nanoparticles Examined with Advanced Fluorescence Microscopy. AB - Plasmon excitation of spherical gold nanoparticles carrying a fluorescent labeled 30 bp dsDNA cargo, with one chain covalently attached through two S-Au bonds to the surface, results in release of the complementary strand as ssDNA that can be examined in situ using high-resolution fluorescence microscopy. The release is dependent on the total energy delivered, but not the rate of delivery, an important property for plasmonic applications in medicine, sensors, and plasmon induced PCR. PMID- 26263159 TI - Down-Regulation of MiR-193a-3p Dictates Deterioration of HCC: A Clinical Real Time qRT-PCR Study. AB - BACKGROUND: Although some recent reports have shown that the expression level of miR-193a varied in different cancers, its role in hepatocellular carcinoma (HCC) remains unidentified. The aim of the current study was to validate the relationship between miR-193a-3p and clinicopathological characteristics in HCC patients. MATERIAL AND METHODS: Expression of miR-193a-3p in 95 HCC cases and their corresponding peritumoral tissues (PT) was examined by using quantitative reverse transcription polymerase chain reaction (qRT-PCR). miR-193a-3p expression and its correlation with a variety of clinicopathological features and patient recurrence were analyzed. RESULTS: The relative level of miR-193a-3p was 3.2028+/ 1.1951 in PT, significantly higher than its expression in HCC tissues (1.5941+/ 0.7079, P<0.001). The area under the curve of underexpression of miR-193a-3p was 0.906 to distinguish HCC from normal liver (95% CI: 0.864-0.948, P<0.001). Expression of miR-193a-3p was negatively correlated to metastasis (r=-0.371, P=0.000), TNM (r=-0.321, P=0.002), respectively. Additionally, the recurrence time was 50.271+/-2.631 months for the low miR-193a-3p level group and 60.132+/ 3.626 months for the high miR-193a-3p level group. However, no significant difference between them was found (chi-square=0.354, P=0.552). CONCLUSIONS: MiR 193a-3p may be a tumor-suppressive miRNA which is down-regulated in HCC tissues. It could be regarded as a predictor for the deterioration of HCC patients. PMID- 26263160 TI - Novel Approach to Identify Potential Bioactive Plant Metabolites: Pharmacological and Metabolomics Analyses of Ethanol and Hot Water Extracts of Several Canadian Medicinal Plants of the Cree of Eeyou Istchee. AB - We evaluated and compared the antidiabetic potential and molecular mechanisms of 17 Cree plants' ethanol extracts (EE) and hot water extracts (HWE) on glucose homeostasis in vitro and used metabolomics to seek links with the content of specific phytochemicals. Several EE of medical plants stimulated muscle glucose uptake and inhibited hepatic G6Pase activity. Some HWE partially or completely lost these antidiabetic activities in comparison to EE. Only R. groenlandicum retained similar potential between EE and HWE in both assays. In C2C12 muscle cells, EE of R. groenlandicum, A. incana and S. purpurea stimulated glucose uptake by activating AMP-activated protein kinase (AMPK) pathway and increasing glucose transporter type 4 (GLUT4) expression. In comparison to EE, HWE of R. groenlandicum exhibited similar activities; HWE of A. incana completely lost its effect on all parameters; interestingly, HWE of S. purpurea activated insulin pathway instead of AMPK pathway to increase glucose uptake. In the liver, for a subset of 5 plants, HWE and EE activated AMPK pathway whereas the EE and HWE of S. purpurea and K. angustifolia also activated insulin pathways. Quercetin-3-O galactoside and quercetin 3-O-alpha-L-arabinopyranoside, were successfully identified by discriminant analysis as biomarkers of HWE plant extracts that stimulate glucose uptake in vitro. More importantly, the latter compound was not identified by previous bioassay-guided fractionation. PMID- 26263161 TI - Protective Effect of Sevoflurane Postconditioning against Cardiac Ischemia/Reperfusion Injury via Ameliorating Mitochondrial Impairment, Oxidative Stress and Rescuing Autophagic Clearance. AB - BACKGROUND AND PURPOSE: Myocardial infarction leads to heart failure. Autophagy is excessively activated in myocardial ischemia/reperfusion (I/R) in rats. The aim of this study is to investigate whether the protection of sevoflurane postconditioning (SPC) in myocardial I/R is through restored impaired autophagic flux. METHODS: Except for the sham control (SHAM) group, each rat underwent 30 min occlusion of the left anterior descending coronary (LAD) followed by 2 h reperfusion. Cardiac infarction was determined by 2,3,5-triphenyltetrazolium chloride triazole (TTC) staining. Cardiac function was examined by hemodynamics and echocardiography. The activation of autophagy was evaluated by autophagosome accumulation, LC3 conversion and p62 degradation. Potential molecular mechanisms were investigated by immunoblotting, real-time PCR and immunofluorescence staining. RESULTS: SPC improved the hemodynamic parameters, cardiac dysfunction, histopathological and ultrastructural damages, and decreased myocardial infarction size after myocardial I/R injury (P < 0.05 vs. I/R group). Compared with the cases in I/R group, myocardial ATP and NAD+ content, mitochondrial function related genes and proteins, and the expressions of SOD2 and HO-1 were increased, while the expressions of ROS and Vimentin were decreased in the SPC group (P < 0.05 vs. I/R group). SPC significantly activated Akt/mTOR signaling, and inhibited the formation of Vps34/Beclin1 complex via increasing expression of Bcl2 protein (P < 0.05 vs. I/R group). SPC suppressed elevated expressions of LC3 II/I ratio, Beclin1, Atg5 and Atg7 in I/R rat, which indicated that SPC inhibited over-activation of autophagy, and promoted autophagosome clearance. Meanwhile, SPC significantly suppressed the decline of Opa1 and increases of Drp1 and Parkin induced by I/R injury (P < 0.05 vs. I/R group). Moreover, SPC maintained the contents of ATP by reducing impaired mitochondria. CONCLUSION: SPC protects rat hearts against I/R injury via ameliorating mitochondrial impairment, oxidative stress and rescuing autophagic clearance. PMID- 26263162 TI - Extensive White Matter Alterations and Its Correlations with Ataxia Severity in SCA 2 Patients. AB - BACKGROUND: Previous studies of SCA2 have revealed significant degeneration of white matter tracts in cerebellar and cerebral regions. The motor deficit in these patients may be attributable to the degradation of projection fibers associated with the underlying neurodegenerative process. However, this relationship remains unclear. Statistical analysis of diffusion tensor imaging enables an unbiased whole-brain quantitative comparison of the diffusion proprieties of white matter tracts in vivo. METHODS: Fourteen genetically confirmed SCA2 patients and aged-matched healthy controls participated in the study. Tract-based spatial statistics were performed to analyze structural white matter damage using two different measurements: fractional anisotropy (FA) and mean diffusivity (MD). Significant diffusion differences were correlated with the patient's ataxia impairment. RESULTS: Our analysis revealed decreased FA mainly in the inferior/middle/superior cerebellar peduncles, the bilateral posterior limb of the internal capsule and the bilateral superior corona radiata. Increases in MD were found mainly in cerebellar white matter, medial lemniscus, and middle cerebellar peduncle, among other regions. Clinical impairment measured with the SARA score correlated with FA in superior parietal white matter and bilateral anterior corona radiata. Correlations with MD were found in cerebellar white matter and the middle cerebellar peduncle. CONCLUSION: Our findings show significant correlations between diffusion measurements in key areas affected in SCA2 and measures of motor impairment, suggesting a disruption of information flow between motor and sensory-integration areas. These findings result in a more comprehensive view of the clinical impact of the white matter degeneration in SCA2. PMID- 26263163 TI - Can the Lamberts and Lambert Submaximal Cycle Test Indicate Fatigue and Recovery in Trained Cyclists? AB - The Lamberts and Lambert Submaximal Cycle Test (LSCT) is a novel test designed to monitor performance and fatigue/recovery in cyclists. Studies have shown the ability to predict performance; however, there is a lack of studies concerning monitoring of fatigue/recovery. In this study, 23 trained male cyclists (age 29 +/- 8 y, VO2max 59.4 +/- 7.4 mL . min(-1) . kg(-1)) completed a training camp. The LSCT was conducted on days 1, 8, and 11. After day 1, an intensive 6-day training period was performed. Between days 8 and 11, a recovery period was realized. The LSCT consists of 3 stages with fixed heart rates of 6 min at 60% and 80% and 3 min at 90% of maximum heart rate. During the stages, power output and rating of perceived exertion (RPE) were determined. Heart-rate recovery was measured after stage 3. Power output almost certainly (standardized mean difference: 1.0) and RPE very likely (1.7) increased from day 1 to day 8 at stage 2. Power output likely (0.4) and RPE almost certainly (2.6) increased at stage 3. From day 8 to day 11, power output possibly (-0.4) and RPE likely (-1.5) decreased at stage 2 and possibly (-0.1) and almost certainly (-1.9) at stage 3. Heart-rate recovery was likely (0.7) accelerated from day 1 to day 8. Changes from day 8 to day 11 were unclear (-0.1). The LSCT can be used for monitoring fatigue and recovery, since parameters were responsive to a fatiguing training and a following recovery period. However, consideration of multiple LSCT variables is required to interpret the results correctly. PMID- 26263164 TI - Characterization of Sin1 Isoforms Reveals an mTOR-Dependent and Independent Function of Sin1gamma. AB - Sin1 or MAPKAP1 is a key component of mTORC2 signaling complex which is necessary for AKT phosphorylation at the S473 and T450 sites, and also for AKT downstream signaling as well. A number of Sin1 splicing variants have been reported that can produce different Sin1 isoforms due to exon skipping or alternative transcription initiation. In this report, we characterized four Sin1 isoforms, including a novel Sin1 isoform due to alternative 3' termination of the exon 9a, termed Sin1gamma. Sin1gamma expression can be detected in multiple adult mouse tissues, and it encodes a C-terminal truncated protein comparing to the full length Sin1beta isoform. In contrast to Sin1beta, Sin1gamma overexpression in Sin1 deficient mouse embryonic fibroblasts has no significant impact on mTORC2 activity or mTORC2 subunits protein level, although it still can interact with mTORC2 components. More interestingly, Sin1gamma was detected in a specific cytosolic location with a distinct feature in structure, and its localization was transiently disrupted during cell cycle. Therefore, Sin1gamma is a novel Sin1 isoform and may have distinct properties in cell signaling and intracellular localization from other Sin1 isoforms. PMID- 26263165 TI - The Role of MKP-1 in the Anti-Proliferative Effects of Glucocorticoids in Primary Rat Pre-Osteoblasts. AB - Glucocorticoid (GC)-induced osteoporosis has been attributed to a GC-induced suppression of pre-osteoblast proliferation. Our previous work identified a critical role for mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) in mediating the anti-proliferative effects of GCs in immortalized pre osteoblasts, but we subsequently found that MKP-1 null mice were not protected against the pathological effects of GCs on bone. In order to reconcile this discrepancy, we have assessed the effects of GCs on proliferation, activation of the MAPK ERK1/2 and MKP-1 expression in primary adipose-derived stromal cells (ADSCs) and ADSC-derived pre-osteoblasts (ADSC-OBs). ADSCs were isolated by means of collagenase digestion from adipose tissue biopsies harvested from adult male Wistar rats. ADSC-OBs were prepared by treating ADSCs with osteoblast differentiation media for 7 days. The effects of increasing concentrations of the GC dexamethasone on basal and mitogen-stimulated cell proliferation were quantified by tritiated thymidine incorporation. ERK1/2 activity was measured by Western blotting, while MKP-1 expression was quantified on both RNA and protein levels, using semi-quantitative real-time PCR and Western blotting, respectively. GCs were strongly anti-proliferative in both naive ADSCs and ADSC-OBs, but had very little effect on mitogen-induced ERK1/2 activation and did not upregulate MKP-1 protein expression. These findings suggest that the anti-proliferative effects of GCs in primary ADSCs and ADSC-OBs in vitro do not require the inhibition of ERK1/2 activation by MKP-1, which is consistent with our in vivo findings in MKP-1 null mice. PMID- 26263166 TI - Anti-inflammatory activity of phlomisoside F isolated from Phlomis younghusbandii Mukerjee. AB - This study was designed to investigate the anti-inflammatory effect of phlomisoside F (PMF) isolated from Phlomis younghusbandii and to explore the possible pharmacological mechanisms. Anti-inflammatory effects of PMF were evaluated by using carrageenan-induced rat paw edema test, dimethylbenzen-induced ear edema test, acetic acid-induced vascular permeability and cotton pellet granuloma test. Furthermore, the releases of pro-inflammatory cytokines (TNF alpha, IL-6 and IL-1beta) were determined by ELISA. To explore the potential mechanisms, expressions of iNOS and COX-2 were determined by quantitative real time PCR and western blotting assays. In addition, the expressions of nuclear p65, cytosolic p65, IkappaB, p38, p-p38, p-ERK1/2, ERK1/2, JNK and p-JNK were determined by western blotting assay. Our results indicated that PMF administered orally could not only significantly decrease rat paw edema in rats and ear edema in mice, but also reduce the vascular permeability in mice and granuloma weights in rats. In vitro, the releases of LPS-induced pro-inflammatory cytokines (TNF alpha, IL-6, IL-1beta) and enzymes (iNOS and COX-2) were decreased significantly by PMF treatment in RAW 264.7 cells. In addition, the LPS-induced up-regulations of nuclear p65, p38, p-p38, p-ERK1/2, JNK and p-JNK proteins in RAW 264.7 cells significantly decreased by PMF, and expressions of cytosolic p65 and IkappaB were obviously up-regulated after treatment with PMF. In conclusion, we suggested that the PMF is a promising potential anti-inflammatory drug, and PMF could down regulate expressions of pro-inflammatory cytokines and mediators by inhibiting the NF-kappaB/MAPK pathways. PMID- 26263167 TI - Anti-TNF-alpha monoclonal antibody reverses psoriasis through dual inhibition of inflammation and angiogenesis. AB - Tumor necrosis factor-alpha (TNF-alpha) antagonists have shown remarkable efficacy in psoriasis; however, the precise mechanisms of action of TNF-alpha blocking agents mainly focus on their neutralizing TNF-alpha and its anti inflammatory effects. In this study, we generated a humanized anti-TNF-alpha monoclonal antibody (IBI303) and suggested a potential mechanism of anti-TNF alpha therapy for psoriasis. The results of SPR and ELISA indicated that IBI303 has a good affinity to TNF-alpha. In vitro, it could suppress TNF-alpha-induced cytotoxicity in WEHI164 cells. In vivo, administration of IBI303 to K14-VEGF transgenic mice led to a significant treatment efficiency in psoriasis in a dose dependent manner. IHC staining and cytokines-ELISA indicated that TNF-alpha inhibition strongly reduced inflammatory cells infiltration and pro-inflammatory cytokines release, accompanied by suppression of inflamed dermal blood vessels. Mechanistically, in order to explain the anti-angiogenesis effect of anti-TNF alpha antibody, the production of cytokine in macrophage conditional medium was measured by ELISA. The result indicated that the massive secretion of TNF-alpha stimulated by LPS in RAW264.7 cell supernatant was markedly neutralized in a dose response manner by IBI303, moreover, the expression of NF-kappaB p65 was down regulated. Mouse endothelial cell tube formation assay showed that anti-TNF-alpha could inhibit blood vessels formation directly and indirectly. Collectively, our study suggested a kind of antipsoriatic mechanism of TNF-alpha inhibitors that is the dual inhibition of inflammation and angiogenesis. PMID- 26263168 TI - Kaempferol alleviates insulin resistance via hepatic IKK/NF-kappaB signal in type 2 diabetic rats. AB - Recent studies show that inflammation underlies the metabolic disorders of insulin resistance and type 2 diabetes mellitus. Since kaempferol, a naturally occurring flavonoid, has been described to have potent anti-inflammatory properties, we investigated whether kaempferol could ameliorate insulin resistance through inhibiting inflammatory responses. The model of diabetic rat was induced by 6-week high-fat diet plus streptozotocin. Animals were orally treated with kaempferol (50 or 150 mg/kg) and aspirin (100mg/kg) for 10 weeks. The results showed that kaempferol ameliorated blood lipids and insulin in an dose-dependent manner. Kaempferol effectively restored insulin resistance induced alteration of glucose disposal by using an insulin tolerance test and the euglycemic-hyperinsulinemic clamp method. Western blotting results showed that KPF inhibited the phosphorylation of insulin receptor substrate-1 (IRS-1), IkB kinase alpha (IKKalpha) and IkB kinase beta (IKKbeta). These effects were accompanied with reduction in nucleic and cytosol levels of nuclear factor kappa beta (NF-kappaB), and further tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels. Aspirin had similar effects. These results provide in vivo evidence that kaempferol-mediated down-regulation of IKK and subsequent inhibition of NF-kappaB pathway activation may be associated with the reduction of hepatic inflammatory lesions, which is contributing to the improvement of insulin signaling defect in diabetes. PMID- 26263169 TI - 6-Gingerol modulates proinflammatory responses in dextran sodium sulfate (DSS) treated Caco-2 cells and experimental colitis in mice through adenosine monophosphate-activated protein kinase (AMPK) activation. AB - BACKGROUND: 6-gingerol has been reported to have anti-inflammatory effects in different experimental settings. The present study aimed at evaluating the effect of 6-gingerol on dextran sodium sulfate (DSS)-induced barrier impairment and inflammation in vitro and in vivo. METHODS: a differentiated Caco-2 monolayer was exposed to DSS and treated with different concentrations of 6-gingerol (0, 1, 5, 10, 50, and 100 MUM). Changes in intestinal barrier function were determined using transepithelial electrical resistance (TEER). The anti-inflammatory activity of 6-gingerol was examined as changes in the expression of proinflammatory cytokine using quantitative real-time PCR. Western blotting was employed to determine the activation of adenosine monophosphate-activated protein kinase (AMPK). Mice with DSS-induced colitis were given different oral dosages of 6-gingerol daily for 14 days. Body weight and colon inflammation were evaluated, and level of proinflammatory cytokines in colon tissues was measured. RESULTS: 6 gingerol treatment was shown to restore impaired intestinal barrier function and to suppress proinflammatory responses in DSS-treated Caco-2 monolayers. We found that AMPK was activated on 6-gingerol treatment in vitro. In animal studies, 6 gingerol significantly ameliorated DSS-induced colitis by restoration of body weight loss, reduction in intestinal bleeding, and prevention of colon length shortening. In addition, 6-gingerol suppressed DSS-elevated production of proinflammatory cytokines (IL-1beta, TNFalpha, and IL-12). CONCLUSION: our findings highlight the protective effects of 6-gingerol against DSS-induced colitis. We concluded that 6-gingerol exerts anti-inflammatory effects through AMPK activation. It is suggested that 6-gingerol has a promising role in treatment of IBD. PMID- 26263170 TI - Alcohol Advertising in Sport and Non-Sport TV in Australia, during Children's Viewing Times. AB - Estimate the amount of alcohol advertising in sport vs. non-sport programming in Australian free-to-air TV and identify children's viewing audience composition at different times of the day. Alcohol advertising and TV viewing audience data were purchased for free-to-air sport and non-sport TV in Australia for 2012. We counted alcohol advertisements in sport and non-sport TV in daytime (6 am-8.29 pm) and evening periods (8.30 pm-11.59 pm) and estimated viewing audiences for children and young adults (0-4 years, 5-13 years, 14-17 years, 18-29 years). During the daytime, most of the alcohol advertising (87%) was on sport TV. In the evening, most alcohol advertising (86%) was in non-sport TV. There was little difference in the mean number of children (0-17 years) viewing TV in the evening (N = 273,989), compared with the daytime (N = 235,233). In programs containing alcohol advertising, sport TV had a greater mean number of alcohol adverts per hour (mean 1.74, SD = 1.1) than non-sport TV (mean 1.35, SD = .94). Alcohol advertising during the daytime, when large numbers of children are watching TV, is predominantly in free-to-air sport TV. By permitting day-time advertising in sport programs and in any programs from 8.30 pm when many children are still watching TV, current regulations are not protecting children from exposure to alcohol advertising. PMID- 26263171 TI - Long-Term Formaldehyde Emissions from Medium-Density Fiberboard in a Full-Scale Experimental Room: Emission Characteristics and the Effects of Temperature and Humidity. AB - We studied formaldehyde emissions from the medium-density fiberboard (MDF) in a full-scale experimental room to approximate emissions in actual buildings. Detailed indoor formaldehyde concentrations and temperature and humidity data were obtained for about 29 months. Temperature, relative humidity (RH), and absolute humidity (AH) ranged over -10.9-31.4 degrees C, 46.5-83.6%, and 1.1 23.1 g/kgair, respectively. Annual cyclical seasonal variations were observed for indoor formaldehyde concentrations and emission rates, exhibiting entirely different characteristics than those in an environmental chamber under constant environmental conditions. The maximum concentration occurred in summer rather than at initial introduction of the material. The concentrations in summer could be a few up to 20 times higher than that in winter, depending on the indoor temperature and humidity conditions. Concentrations decreased by 20-65% in corresponding months of the second year. Indoor formaldehyde concentrations were positively correlated with temperature and AH but were poorly correlated with RH. The combined effects of temperature and AH on formaldehyde emissions from MDF in actual buildings were verified. These detailed long-term experimental results could be used with environmental chamber measurement data to scale up and validate emission models from chambers held at constant conditions to actual buildings. PMID- 26263172 TI - Monitoring the Invasion of Spartina alterniflora from 1993 to 2014 with Landsat TM and SPOT 6 Satellite Data in Yueqing Bay, China. AB - The exotic plant Spartina alterniflora was introduced to Yueqing Bay more than 20 years ago for tidal land reclamation and as a defense against typhoons, but it has rapidly expanded and caused enormous ecological consequences. Mapping the spread and distribution of S. alterniflora is the first step toward understanding the factors that determine the population expansion patterns. Remote sensing is a promising tool to monitor the expansion of S. alterniflora. Twelve Landsat TM images and Support Vector Machine (SVM) were used to delineate the invasion of S. alterniflora from 1993 to 2009, and SPOT 6 images and Object-Based Image Analysis (OBIA) were used to map the distribution of S. alterniflora in 2014. In situ data and Unmanned Aerial Vehicle (UAV) images were used as supplementary data. S. alterniflora spread rapidly in Yueqing Bay over the past 21 years. Between 1993 and 2009, the area of S. alterniflora increased by 608 times (from 4 to 2432 ha). The rapid expansion of S. alterniflora covered almost all of the bare mudflats around the mangrove forests and the cultivated mudflats. However, from 2009 to 2014, the rate of expansion of S. alterniflora began to slow down in Yueqing Bay, and the total area of S. alterniflora in Yantian decreased by 275 ha. These phenomena can be explained by the landscape changes and ecological niches. Through the expansion of S. alterniflora, it was found that the ecological significance and environmental impact of S. alterniflora was different in different regions in Yueqing Bay. The conservation plans for Yueqing Bay should consider both the positive and negative effects of S. alterniflora, and the governmental policy should be based on the different circumstances of the regions. PMID- 26263174 TI - Oxidative stress responses induced by uranium exposure at low pH in leaves of Arabidopsis thaliana plants. AB - Anthropogenic activities have led to a widespread uranium (U) contamination in many countries. The toxic effects of U at the cellular level have mainly been investigated at a pH around 5.5, the optimal pH for hydroponically grown plants. However, since the speciation of U, and hence its toxicity, is strongly dependent on environmental factors such as the pH, it is important to investigate the effects of U at different environmentally relevant pH levels. Although U is poorly translocated from the roots to the shoots, resulting in a low U concentration in the leaves, it has been demonstrated that toxic effects in the leaves were already visible after 1 day exposure at pH 5.5, although only when exposed to relatively high U concentrations (100 MUM). Therefore, the present study aimed to analyse the effects of different U concentrations (ranging from 0 to 100 MUM) at pH 4.5 in leaves of Arabidopsis thaliana plants. Results indicate that U induces early senescence in A. thaliana leaves as was suggested by a decreased expression of CAT2 accompanied by an induction of CAT3 expression, a decreased CAT capacity and an increased lipid peroxidation. In addition, miRNA398b/c is involved in the regulation of the SOD response in the leaves. As such, an increased MIR398b/c expression was observed leading to a decreased transcript level of CSD1/2. Finally, the biosynthesis of ascorbate was induced after U exposure. This can point towards an important role for this metabolite in the scavenging of reactive oxygen species under U stress. PMID- 26263173 TI - Deficiency of Lipoprotein Lipase in Neurons Decreases AMPA Receptor Phosphorylation and Leads to Neurobehavioral Abnormalities in Mice. AB - Alterations in lipid metabolism have been found in several neurodegenerative disorders, including Alzheimer's disease. Lipoprotein lipase (LPL) hydrolyzes triacylglycerides in lipoproteins and regulates lipid metabolism in multiple organs and tissues, including the central nervous system (CNS). Though many brain regions express LPL, the functions of this lipase in the CNS remain largely unknown. We developed mice with neuron-specific LPL deficiency that became obese on chow by 16 wks in homozygous mutant mice (NEXLPL-/-) and 10 mo in heterozygous mice (NEXLPL+/-). In the present study, we show that 21 mo NEXLPL+/- mice display substantial cognitive function decline including poorer learning and memory, and increased anxiety with no difference in general motor activities and exploratory behavior. These neurobehavioral abnormalities are associated with a reduction in the 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl) propanoic acid (AMPA) receptor subunit GluA1 and its phosphorylation, without any alterations in amyloid beta accumulation. Importantly, a marked deficit in omega-3 and omega-6 polyunsaturated fatty acids (PUFA) in the hippocampus precedes the development of the neurobehavioral phenotype of NEXLPL+/- mice. And, a diet supplemented with n 3 PUFA can improve the learning and memory of NEXLPL+/- mice at both 10 mo and 21 mo of age. We interpret these findings to indicate that LPL regulates the availability of PUFA in the CNS and, this in turn, impacts the strength of synaptic plasticity in the brain of aging mice through the modification of AMPA receptor and its phosphorylation. PMID- 26263176 TI - Total body water measurement using the 2H dilution technique for the assessment of body composition of Kuwaiti children. AB - OBJECTIVE: The 2H dilution technique is the reference method to estimate total body water for body composition assessment. The aims of the present study were to establish the total body water technique at the Kuwait Institute for Scientific Research and assess body composition of Kuwaiti children. DESIGN: The isotope ratio mass spectrometer was calibrated with defined international reference water standards. A non-random sampling approach was used to recruit a convenience sample of Kuwaiti children. A dose of 2H2O, 1-3 g, was consumed after an overnight fast and 2H enrichment in baseline and post-dose urine samples was measured. Total body water was calculated and used to estimate fat-free mass. Fat mass was estimated as body weight minus fat-free mass. SETTING: The total body water study was implemented in primary schools. SUBJECTS: Seventy-five boys and eighty-three girls (7-9 years). RESULTS: Measurements of the isotope ratio mass spectrometer were confirmed to be accurate and precise. Children were classified as normal weight, overweight or obese according to the WHO based on BMI-for-age Z scores. Normal-weight and overweight girls had significantly higher percentage body fat (median (range): 32.4 % (24.7-39.3 %) and 38.3 % (29.3-44.2 %), respectively) compared with boys (median (range): 26.5 % (14.2-37.1 %) and 34.6 % (29.9-40.2 %), respectively). No gender difference was found in obese children (median 46.5 % v. 45.6 %). CONCLUSIONS: The establishment of a state-of-the-art stable isotope laboratory for assessment of body composition provides an opportunity to explore a wide range of applications to better understand the relationship between body size, body composition and risk of developing non communicable diseases in Kuwait. PMID- 26263175 TI - Neuronal Survival, Morphology and Outgrowth of Spiral Ganglion Neurons Using a Defined Growth Factor Combination. AB - OBJECTIVES: The functionality of cochlear implants (CI) depends, among others, on the number and excitability of surviving spiral ganglion neurons (SGN). The spatial separation between the SGN, located in the bony axis of the inner ear, and the CI, which is inserted in the scala tympani, results in suboptimal performance of CI patients and may be decreased by attracting the SGN neurites towards the electrode contacts. Neurotrophic factors (NTFs) can support neuronal survival and neurite outgrowth. METHODS: Since brain-derived neurotrophic factor (BDNF) is well known for its neuroprotective effect and ciliary neurotrophic factor (CNTF) increases neurite outgrowth, we evaluated if the combination of BDNF and CNTF leads to an enhanced neuronal survival with extended neurite outgrowth. Both NTFs were added in effective high concentrations (BDNF 50 ng/ml, CNTF 100 ng/ml), alone and in combination, to cultured dissociated SGN of neonatal rats for 48 hours. RESULTS: The neuronal survival and neurite outgrowth were significantly higher in SGN treated with the combination of the two NTFs compared to treatment with each factor alone. Additionally, with respect to the morphology, the combination of BDNF and CNTF leads to a significantly higher number of bipolar neurons and a decreased number of neurons without neurites in culture. CONCLUSION: The combination of BDNF and CNTF shows a great potential to increase the neuronal survival and the number of bipolar neurons in vitro and to regenerate retracted nerve fibers. PMID- 26263177 TI - Temperature- and pH-Dependent Shattering: Insoluble Fatty Ammonium Phosphate Films at Water-Oil Interfaces. AB - We study the films formed by tetradecylamine (TDA) at the water-dodecane interface in the presence of hydrogen phosphate ions. Using Fourier transform infrared spectroscopy (FTIR), interfacial shear rheology, confocal fluorescence microscopy, cryo-scanning electron microscopy (cryo-SEM), and small-angle neutron scattering (SANS), we find that between pH 5 and 8 tetradecylammonium cations bind to hydrogen phosphate anions to form needle-shaped crystallites of tetradecylammonium hydrogen phosphate (TAHP). These crystallites self-assemble into films with a range of morphologies; below pH 7, they form brittle, continuous sheets, and at pH 8, they form lace-like networks that deform plastically under shear. They are also temperature-responsive: when the system is heated, the film thins and its rheological moduli drop. We find that the temperature response is caused by dissolution of the film in to the bulk fluid phases. Finally, we show that these films can be used to stabilize temperature responsive water-in-oil emulsions with potential applications in controlled release of active molecules. PMID- 26263178 TI - Efficient Generation of Plasmacytoid Dendritic Cell from Common Lymphoid Progenitors by Flt3 Ligand. AB - Dendritic cells (DCs), including conventional DCs (cDCs) and plasmacytoid DCs (pDCs) are critical for initiating and controlling the immune response. However, study of DC, particularly pDC, function is hampered by their low frequency in lymphoid organs, and existing methods for in vitro DC generation preferentially favor the production of cDCs over pDCs. Here, we demonstrated that pDCs could be efficiently generated in vitro from common lymphoid progenitors (CLPs) using Flt3 ligand (FL) in three different culture systems, namely feeder-free, BM-feeder and AC-6-feeder. This was in stark contrast to common DC progenitors (CDPs), in which cDCs were prominently generated under the same conditions. Moreover, the efficiency and function of pDCs generated from these three systems varied. While AC-6 system showed the greatest ability to support pDC development from CLPs, BM feeder system was able to develop pDCs with better functionality. pDCs could also be expanded in vivo using hydrodynamic gene transfer of FL, which was further enhanced by the combined treatment of FL and IFN-alpha. Interestingly, IFN-alpha selectively promoted the proliferation of CLPs and not CDPs, which might contribute to enhanced pDC development. Together, we have defined conditions for in vitro and in vivo generation of pDCs, which may be useful for investigating the biology of pDCs. PMID- 26263180 TI - Circumscription and Taxonomic Arrangement of Nigroboletus roseonigrescens Gen. Et Sp. Nov., a New Member of Boletaceae from Tropical South-Eastern China. AB - Nigroboletus is proposed as a novel genus in family Boletaceae, subfamily Boletoideae, to include N. roseonigrescens, a new boletoid species from tropical environment in south-eastern China. Detailed morphological description, color pictures of both fresh basidiomes in habitat and dried material along with photomicrographs and line drawings of the main anatomical features are provided, supported by a comprehensive phylogeny based on multigene molecular analysis (nrITS, nrLSU, rpb1, rpb2 and tef1-alpha datasets). Taxonomic placement and evolutionary relationships of Nigroboletus are investigated. PMID- 26263179 TI - The Genomic Legacy of the Transatlantic Slave Trade in the Yungas Valley of Bolivia. AB - During the period of the Transatlantic Slave Trade (TAST) some enslaved Africans were forced to move to Upper Peru (nowadays Bolivia). At first they were sent to Potosi, but later to the tropical Yungas valley where the Spanish colonizers established a so-called "hacienda system" that was based on slave labor, including African-descendants. Due to their isolation, very little attention has been paid so far to 'Afro-Bolivian' communities either within the research field of TAST or in genetic population studies. In this study, a total of 105 individuals from the Yungas were sequenced for their mitochondrial DNA (mtDNA) control region, and mitogenomes were obtained for a selected subset of these samples. We also genotyped 46 Ancestry Informative Markers (AIM) in order to investigate continental ancestry at the autosomal level. In addition, Y chromosome STR and SNP data for a subset of the same individuals was also available from the literature. The data indicate that the partitioning of mtDNA ancestry in the Yungas differs significantly from that in the rest of the country: 81% Native American, 18% African, and 1% European. Interestingly, the great majority of 'Afro-descendant' mtDNA haplotypes in the Yungas (84%) concentrates in the locality of Tocana. This high proportion of African ancestry in the Tocana is also manifested in the Y-chromosome (44%) and in the autosomes (56%). In sharp contrast with previous studies on the TAST, the ancestry of about 1/3 of the 'Afro-Bolivian' mtDNA haplotypes can be traced back to East and South East Africa, which may be at least partially explained by the Arab slave trade connected to the TAST. PMID- 26263181 TI - Molecular Recognition and Visual Detection of G-Quadruplexes by a Dicarbocyanine Dye. AB - The interactions of a dicarbocyanine dye 3,3'-diethylthiadicarbocyanine, DiSC2(5), with DNA G-quadruplexes were studied by means of a combination of various spectroscopic techniques. Aggregation of excess dye as a result of its positive charge is promoted by the presence of the polyanionic quadruplex structure. Specific high-affinity binding to the parallel quadruplex of the MYC promoter sequence involves stacking of DiSC2(5) on the external G-tetrads; the 5' terminal tetrad is the favored binding site. Significant energy transfer between DNA and the dye in the UV spectral region is observed upon DiSC2(5) binding. The transfer efficiency strongly depends on the DNA secondary structure as well as on the G-quadruplex topology. These photophysical features enable the selective detection of DNA quadruplexes through sensitized DiSC2(5) fluorescence in the visible region. PMID- 26263182 TI - Diagnostic endoscopy of the navicular bursa using a needle endoscope by direct or transthecal approach: A comparative cadaver study. AB - OBJECTIVES: To compare the practicability, visualization of structures, and iatrogenic damage of direct and transthecal approaches to the navicular bursa for diagnostic needle endoscopy. STUDY DESIGN: Descriptive study. SAMPLE POPULATION: Equine cadaver forelimbs (n = 30). METHODS: Direct and transthecal approaches for insertion of a needle endoscope into the navicular bursa were performed. Video recordings of endoscopic procedures were assessed to determine all structures visualized within the navicular bursa. Number of attempts to gain access to the navicular bursa and total time for insertion and examination were recorded. Distribution and severity of iatrogenic lesions were assessed and scored after dissection. RESULTS: There were no statistical differences for number of attempts or time needed for insertion and examination between direct and transthecal approaches. The direct approach offered significantly increased visibility of the ipsilateral abaxial and proximal margins of the navicular bone, and ipsilateral collateral sesamoidean ligament. Iatrogenic lesions were superficial and focal, regardless of approach taken, or whether a blunt or sharp trocar tip was used. CONCLUSIONS: The direct approach provided significantly better visualization of the ipsilateral structures within the navicular bursa compared to the transthecal approach. Needle endoscopy offers a reliable technique to evaluate the navicular bursa and may complement or replace other diagnostic modalities in horses with lameness localized to the navicular region. PMID- 26263184 TI - Gate-Free Electrical Breakdown of Metallic Pathways in Single-Walled Carbon Nanotube Crossbar Networks. AB - Aligned single-walled carbon nanotubes (SWNTs) synthesized by the chemical vapor deposition (CVD) method have exceptional potential for next-generation nanoelectronics. However, the coexistence of semiconducting (s-) and metallic (m ) SWNTs remains a considerable challenge since the latter causes significant degradation in device performance. Here we demonstrate a facile and effective approach to selectively break all m-SWNTs by stacking two layers of horizontally aligned SWNTs to form crossbars and applying a voltage to the crossed SWNT arrays. The introduction of SWNT junctions amplifies the disparity in resistance between s- and m-pathways, leading to a complete deactivation of m-SWNTs while minimizing the degradation of the semiconducting counterparts. Unlike previous approaches that required an electrostatic gate to achieve selectivity in electrical breakdown, this junction process is gate-free and opens the way for straightforward integration of thin-film s-SWNT devices. Comparison to electrical breakdown in junction-less SWNT devices without gating shows that this junction based breakdown method yields more than twice the average on-state current retention in the resultant s-SWNT arrays. Systematic studies show that the on/off ratio can reach as high as 1.4 * 10(6) with a correspondingly high retention of on-state current compared to the initial current value before breakdown. Overall, this method provides important insight into transport at SWNT junctions and a simple route for obtaining pure s-SWNT thin film devices for broad applications. PMID- 26263183 TI - miR-98 and its host gene Huwe1 target Caspase-3 in Silica nanoparticles-treated male germ cells. AB - Silica nanoparticles (NP) is one of the most commonly used nanomaterials with potential health hazards. However, the effects of Silica NP on germ cells and the underlying mechanisms are still unclear. In this study, GC-2 and TM-4, which are two different types of male germ cells were exposed to Silica NP for 24h, and then general cytotoxicity and multi-parameter cytotoxicity were evaluated. Our results showed that Silica NP could induce apoptosis in GC-2 cells. Transmission electron microscopy (TEM) results showed that Silica NP was localized in the lysosomes of GC-2 cells. High content screening (HCS) showed that Silica NP exposure could increased cell permeabilization and decreased mitochondrial membrane potential in GC-2 cells. The mRNA and protein levels of apoptosis markers (Bax, Caspase-3, Caspase-9) in GC-2 cells were significantly increased, while Bcl-2 was decreased. Accordingly, the expression level of miR-98, which can regulate Caspase-3, was significantly decreased. Huwe1, the host gene of miR-98, was positively associated with miR-98 expression after Silica NP exposure. Dual luciferase reporter assay suggested that miR-98 directly targets Caspase-3. These results suggest that Silica NP induces apoptosis via loss of mitochondrial membrane potential and Caspase-3 activation, while miR-98 plays key role in modulating this effect. PMID- 26263185 TI - Neuronal acid-induced [Zn2+]i elevations calibrated using the low-affinity ratiometric probe FuraZin-1. AB - The experiments were carried out on primary cultures of murine cortical neurons from cryopreserved preparations obtained from embryonic-day-16 fetuses. To calibrate acid-induced intracelluar [Zn(2+) ] ([Zn(2+) ]i ) elevations, a low affinity (Kd = 39 MUM at pH 6.1) ratiometric Zn(2+) probe, FuraZin-1, was used. A pHi drop from 7.2 to 6.1 caused [Zn(2+) ]i elevations reaching 2 MUM; when the thiol-reactive agent N-ethylmaleimide (NEM) was subsequently applied, [Zn(2+) ]i increased further to 5.6 MUM; analogous acid- and NEM-induced [Zn(2+) ]i elevations could also be detected but not calibrated, using the high affinity Zn(2+) probe FluoZin-3. The data indicate that NEM causes Zn(2+) release from ligands that chelate Zn(2+) at pH 6.1. ATP could also chelate Zn(2+) at pH 6.1 because its pKa is about 6.8. Therefore, it was tested whether an ATP depletion affects the acid-induced [Zn(2+) ]i elevations. The ATP depletion was induced by inhibiting mitochondrial and glycolytic ATP production. Interestingly, an almost complete ATP depletion (confirmed using a luciferin/luciferase assay) failed to affect the acid-induced [Zn(2+) ]i increases. These data suggest that the total amount of Zn(2+) accumulated in intracellular ATP-dependent stores (Zn(2+) -ATP complexes and organelles that accumulate Zn(2+) in an ATP-dependent manner) is negligible compared to the amount of Zn(2+) accumulated in the acid-sensitive intracellular ligands. In vitro, upon acidification, Zn(2+) -cysteine complexes release Zn(2+) and ATP chelates the released Zn(2+) . However, in vivo (cultured neurons), an ATP depletion failed to enhance acid-induced [Zn(2+) ]i elevations. These [Zn(2+) ]i elevations were calibrated using a low affinity ratiometric probe FuraZin-1; they reached 2 uM levels and increased to 5 uM when a thiol reactive agent, N-ethylmaleimide, compromised Zn(2+) binding by cysteines. PMID- 26263188 TI - Editorial: Agroecology for producing goods and services in sustainable animal farming systems. PMID- 26263187 TI - Optimization of a Stable Linker Involved DEVD Peptide-Doxorubicin Conjugate That Is Activated upon Radiation-Induced Caspase-3-Mediated Apoptosis. AB - The current study demonstrates the process of selecting an optimal structure for a caspase-3-cleavable doxorubicin prodrug that could be synthesized by simple chemistry in high yields. The prodrug was intended to activate in the presence of caspase-3, whose expression can be exogenously regulated by inducing apoptosis with radiation therapy at a specific site of interest. For this purpose, doxorubicin was conjugated with a DEVD peptide via a heterobifunctional linker. Since the active form of the prodrug comprises the linker besides doxorubicin, we tested several different linkers and selected EMCS based on the examination of its in vitro biological activities. Consequently, DEVD-cysteamide-EMCS doxorubicin was synthesized as the final compound. According to the various in vitro and in vivo studies, the synthesized prodrug was highly selective for tumors when coupled with radiation therapy, with the added benefit of ease of production. PMID- 26263186 TI - The Influence of Prior Learning Experience on Pollinator Choice: An Experiment Using Bumblebees on Two Wild Floral Types of Antirrhinum majus. AB - Understanding how pollinator behavior may influence pollen transmission across floral types is a major challenge, as pollinator decision depends on a complex range of environmental cues and prior experience. Here we report an experiment using the plant Antirrhinum majus and the bumblebee Bombus terrestris to investigate how prior learning experience may affect pollinator preferences between floral types when these are presented together. We trained naive bumblebees to forage freely on flowering individuals of either A. majus pseudomajus (magenta flowers) or A. majus striatum (yellow flowers) in a flight cage. We then used a Y-maze device to expose trained bumblebees to a dual choice between the floral types. We tested the influence of training on their choice, depending on the type of plant signals available (visual signals, olfactory signals, or both). Bumblebees had no innate preference for either subspecies. Bumblebees trained on the yellow-flowered subspecies later preferred the yellow type, even when only visual or only olfactory signals were available, and their preference was not reinforced when both signal types were available. In contrast, bumblebees trained on the magenta-flowered subspecies showed no further preference between floral types and took slightly more time to make their choice. Since pollinator constancy has been observed in wild populations of A. majus with mixed floral types, we suggest that such constancy likely relies on short-term memory rather than acquired preference through long-term memory induced by prior learning. PMID- 26263189 TI - Intensification of cattle ranching production systems: socioeconomic and environmental synergies and risks in Brazil. AB - Intensification of Brazilian cattle ranching systems has attracted both national and international attention due to its direct relation with Amazon deforestation on the one hand and increasing demand of the global population for meat on the other. Since Brazilian cattle ranching is predominantly pasture-based, we particularly focus on pasture management. We summarize the most recurrent opportunities and risks associated with pasture intensification that are brought up within scientific and political dialogues, and discuss them within the Brazilian context. We argue that sustainable intensification of pasturelands in Brazil is a viable way to increase agricultural output while simultaneously sparing land for nature. Since environmental degradation is often associated with low-yield extensive systems in Brazil, it is possible to obtain higher yields, while reversing degradation, by adopting practices like rotational grazing, incorporation of legumes and integrated crop-livestock-forestry systems. Technical assistance is however essential, particularly for small- and medium scale farmers. Sound complementary policies and good governance must accompany these measures so that a 'rebound effect' does not lead to increased deforestation and other adverse social and environmental impacts. It is also important that animal welfare is not compromised. Although the discussion is presented with respect to Brazil, some aspects are relevant to other developing countries. PMID- 26263191 TI - Localising livestock protein feed production and the impact on land use and greenhouse gas emissions. AB - Livestock farmers in Sweden usually grow feed grains for livestock but import protein feed from outside Sweden. Aside from the economic implications, some environmental issues are associated with this practice. We used life cycle assessment to evaluate the impact of local protein feed production on land use and greenhouse gas emissions, compared with the use of imported protein feed, for pig meat and dairy milk produced in Sweden. Our results showed that local production reduced greenhouse gas emissions by 4.5% and 12%, respectively, for pigs and dairy cows. Land use for feed production in Sweden increased by 11% for pigs and 25% for dairy cows, but total land use decreased for pig production and increased for dairy milk production. Increased protein feed cultivation in Sweden decreased inputs needed for animal production and improved some ecological processes (e.g. nutrient recycling) of the farm systems. However, the differences in results between scenarios are relatively small and influenced to an extent by methodological choices such as co-product allocation. Moreover, it was difficult to assess the contribution of greenhouse emissions from land use change. The available accounting methods we applied did not adequately account for the potential land use changes and in some cases provided conflicting results. We conclude that local protein feed production presents an opportunity to reduce greenhouse gas emissions but at a cost of increasing land occupation in Sweden for feed production. PMID- 26263190 TI - Mixed grazing systems of goats with cattle in tropical conditions: an alternative to improving animal production in the pasture. AB - Mixed grazing systems combining sheep and cattle have shown better growth performance for one or both species. This observation has been attributed to their complementary feeding behaviour and the reduced host infection by gastrointestinal nematodes. Less attention has been paid to mixed grazing systems combining goats and cattle. Here, continuously grazing goats mixed with cattle (M) were compared with control goats reared alone (C) under tropical conditions. The comparison was conducted with gastrointestinal nematode-infected (I) and non infected (nI) goats. Thus, the four treatments were cattle with gastrointestinal nematode-infected goats (MI), gastrointestinal nematode-infected goats alone (CI), cattle with non-infected goats (MnI) and non-infected goats (CnI). Average daily gain (ADG, g/day) and grass production were measured for the four groups of animals (six goats and two heifers treated with MI or MnI) grazing for 3 months on 4 subplots. Monthly measurements were performed over 5-day periods. This pattern was replicated in space for a second set of four subplots and in time for six successive cohorts of animals (bands 1 to 6). The ADG of goats in mixed grazing conditions was higher than controls irrespective of the infection status (32.6 v. 18.4 g/day for MI v. CI; 44.2 v. 33.5 g/day for MnI v. CnI). Concomitantly, the average biomass was lower for mixed grazing animals compared with controls (174 v. 170 for MI and MnI; 235 v. 208 for CI and CnI, respectively), suggesting better use of the sward. For daily BW gain (g/kg DM), mixed grazing also yielded better results than the control (1.88 v. 0.52 g BW/kg DM per day for MI v. CI; 2.08 v. 1.47 g BW/kg DM per day for MnI and CnI). Mixed grazing of goats and heifers offers a promising alternative for increasing goat and overall animal production as well as improving the management of pastures. PMID- 26263192 TI - Dynamic Optical Properties of CH3NH3PbI3 Single Crystals As Revealed by One- and Two-Photon Excited Photoluminescence Measurements. AB - The dynamic optical properties of perovskite CH3NH3PbI3 single crystals were studied by means of time-resolved photoluminescence (PL) spectroscopy at room temperature. The PL peak under one-photon excitation exhibits a red-shift with elapsing time, while two-photon PL is time-independent and appears at lower energy levels. The low-energy two-photon PL can be attributed to emissions from the localized states because of strong band-to-band absorption and photon re absorption of the emitted light in the interior region. We revealed that the PL behaviors can be explained by the diffusion of photocarriers generated in the near-surface region to the interior region. The excitation fluence dependence of the one-photon PL dynamics is also discussed in terms of the electron-hole radiative recombination and carrier diffusion effects. PMID- 26263193 TI - COPD Multidisciplinary Team Meetings in the United Kingdom: Health Care Professionals' Perceptions of Aims and Structure. AB - Over the last 10 years, community and hospital-based multidisciplinary teams (MDTs) have been set up for the management of patients with chronic obstructive pulmonary disease (COPD) in the UK. Meetings of the MDTs have become a regular occurrence, mostly on healthcare professionals' own initiatives. There are no standardized methods to conduct an MDT meeting, and although cancer MDT meetings are widely implemented, the value and purpose of COPD MDT meetings are less clear. Therefore, the aim of this study was to conduct a cross-sectional descriptive online survey to explore COPD MDT members' perceptions of the purpose and usefulness of MDT meetings, and to identify suggestions or requirements to improve the meetings. In total, we received 68 responses from 10 MDTs; six teams (n = 36 members) were located in London and four (n = 32 members) outside. Analysis of the replies by two independent researchers found that MDT meetings aim to optimise management and improve pathways for respiratory patients by improving communication between providers across settings and disciplines. Education of the MDT members also occurs with the aim of safer practice. Discussed patients are characterised by (multiple) co-morbidities, frequent exacerbations and admissions, social and mental health problems, unclear diagnosis and suboptimal responses to interventions. Members reported participating in a COPD MDT as very useful (74%) or useful (20%). Meetings could be improved by ensuring attendance through requirement in job plans, by clear documentation and sharing of derived plans with a wider audience including general practitioners and patients. PMID- 26263194 TI - Sequence-dependent cluster analysis of biomineralization peptides. AB - A reliable and statistically valid classification of biomineralization peptides is herein presented. 27 biomineralization peptides (BMPep) were randomly selected as representative samples to establish the classification system using k-means method. These biomineralization peptides were either discovered through isolation from various organisms or via phage display. Our findings show that there are two types of biomineralization peptides based on their length, molecular weight, heterogeneity, and aliphatic residues. Type-1 BMPeps are more commonly found and exhibit higher values for these significant clustering variables. In contrast are the type-2 BMPeps, which have lower values for these parameters and are less common. Through our clustering analysis, a more efficient and systematic approach in BMPep selection is possible since previous methods of BMPep classification are unreliable. PMID- 26263195 TI - Inhibitory effects of N,N,N-trimethyl phytosphingosine-iodide on melanogenesis via ERK activation-mediated MITF degradation. AB - N,N,N-trimethyl phytosphingosine-iodide (TMP) was recently developed as an antitumor agent. We examined the effects of TMP on melanogenesis and its related signaling pathways in normal human melanocytes. Our results showed that melanin is significantly reduced in a dose-dependent manner in both cells following liposomal TMP treatment. We also investigated changes in the phosphorylation of extracellular signal-regulated kinase (ERK), which is related to the degradation of microphthalmia-associated transcription factor (MITF). Our results indicated that liposomal TMP treatment leads to the phosphorylation of ERK, which reduces both MITF and tyrosinase protein levels. Treatment with PD98059, an ERK pathway specific inhibitor, restored liposomal TMP-induced reductions in melanin, abrogated reductions in tyrosinase activity, and downregulated MITF and tyrosinase protein. In conclusion, these results suggest that the inhibitory effects of TMP on melanogenesis are due to MITF and tyrosinase downregulation via ERK activation. PMID- 26263196 TI - Sequence and structural diversity of transferrin receptors in Gram-negative porcine pathogens. AB - Actinobacillus pleuropneumoniae, Actinobacillus suis, and Haemophilus parasuis are bacterial pathogens from the upper respiratory tract that are responsible for a substantial burden of porcine disease. Although reduction of disease has been accomplished by intensive management practices, immunization remains an important strategy for disease prevention, particularly when intensive management practices are not feasible or suitable. An attractive target for vaccine development is the surface receptor involved in acquiring iron from host transferrin, since it is common to all three pathogenic species and has been shown to be essential for survival and disease causation. It has also recently been demonstrated that an engineered antigen derived from the lipoprotein component of the receptor, transferrin-binding protein B (TbpB), was more effective at preventing infection by H. parasuis than a commercial vaccine product. This study was initiated to explore the genetic and immunogenic diversity of the transferrin receptor system from these species. Nucleic acid sequences were obtained from a geographically and temporally diverse collection of isolates, consisting of 41 A. pleuropneumoniae strains, 30 H. parasuis strains, and 2 A. suis strains. Phylogenetic analyses demonstrated that the receptor protein sequences cluster independently of species, suggesting that there is genetic exchange between these species such that receptor-based vaccines should logically target all three species. To evaluate the cross-reactive response of TbpB-derived antigens, pigs were immunized with the intact TbpB, the TbpB N-lobe and the TbpB C-lobe from A. pleuropneumoniae strain H49 and the resulting sera were tested against a representative panel of TbpBs; demonstrating that the C-lobe induces a broadly cross-reactive response. Overall our results indicate that there is a common reservoir for transferrin receptor antigenic variation amongst these pathogens. While this could present a challenge to future vaccine development, our results suggest a rationally designed TbpB-based vaccine may provide protection against all three pathogens. PMID- 26263197 TI - Polymeric micro/nanoparticles: Particle design and potential vaccine delivery applications. AB - Particle based adjuvant showed promising signs on delivering antigen to immune cells and acting as stimulators to elicit preventive or therapeutic response. Nevertheless, the wide size distribution of available polymeric particles has so far obscured the immunostimulative effects of particle adjuvant, and compromised the progress in pharmacological researches. To conquer this hurdle, our research group has carried out a series of researches regarding the particulate vaccine, by taking advantage of the successful fabrication of polymeric particles with uniform size. In this review, we highlight the insight and practical progress focused on the effects of physiochemical property (e.g. particle size, charge, hydrophobicity, surface chemical group, and particle shape) and antigen loading mode on the resultant biological/immunological outcome. The underlying mechanisms of how the particles-based vaccine functioned in the immune system are also discussed. Based on the knowledge, particles with high antigen payload and optimized attributes could be designed for expected adjuvant purpose, leading to the development of high efficient vaccine candidates. PMID- 26263198 TI - The incidence of childhood and adolescent seizures in the UK from 1999 to 2011: A retrospective cohort study using the Clinical Practice Research Datalink. AB - BACKGROUND: In postmarketing vaccine surveillance, adverse events observed in a vaccinated population are compared to the number expected based on a background incidence rate. The background rate should be accurate and obtained from a population comparable to the one vaccinated. Such rates are often not available. METHODS: The incidence rate of generalised convulsive, febrile and afebrile seizures was estimated in individuals born after 01-January-1998 and aged between 2 months and 15 years of age using the UK Clinical Practice Research Datalink (1999-2011). RESULTS: The study population consisted of 1532,992 individuals (4917,369 person years (PY) of follow up). A total of 28,917 generalised convulsive seizure events were identified during follow-up, the overall incidence rate was 5.88 per 1000PY. Age specific rates increased sharply from 4/1000PY at 2 months of age, peaked at 19/1000PY at 16 months and decreased until approximately 6 years of age at which point they became relatively stable at 2/1000PY. 67% of GCSs were categorised as febrile: 56% using Read codes, 11% using free text. Febrile seizures accounted for the age trend in GCS, with rates peaking at 16.1/1000PY at 16 months of age while afebrile seizure rates remained relatively stable across all ages (24 seizures per 1000PY). Analysis by first occurrence of febrile seizure showed a similar pattern, comparable to published studies on the incidence of seizures in childhood. DISCUSSION: The rates reported in this study could be used in the postmarketing surveillance of infant vaccines. However, given the variation across strata, and the potential underascertainment of seizure events presenting to A&E, care must be taken when interpreting and using these rates. PMID- 26263199 TI - Introduction. Maternal immunization - Promises and concerns. AB - In this issue of Vaccine, the maternal immunization platform as an approach to protect mothers and infants against diverse pathogens is presented. Potential vaccine targets and the safety, science, trial designs, ethical considerations, and international perspectives focusing on low and middle income countries (LMIC) are discussed. This information provides a timely update because maternal immunization is increasingly being considered as an intervention to prevent maternal and/or neonatal disease. Prioritization of vaccine targets for maternal immunization by researchers, public health officials and health care workers needs to begin now. PMID- 26263200 TI - Catching-up with pentavalent vaccine: Exploring reasons behind lower rotavirus vaccine coverage in El Salvador. AB - Rotavirus vaccine was introduced in El Salvador in 2006 and is recommended to be given concomitantly with DTP-HepB-Haemophilus influenzae type b (pentavalent) vaccine at ages 2 months (upper age limit 15 weeks) and 4 months (upper age limit 8 months) of age. However, rotavirus vaccination coverage continues to lag behind that of pentavalent vaccine, even in years when national rotavirus vaccine stock outs have not occurred. We analyzed factors associated with receipt of oral rotavirus vaccine among children who received at least 2 doses of pentavalent vaccine in a stratified cluster survey of children aged 24-59 months conducted in El Salvador in 2011. Vaccine doses included were documented on vaccination cards (94.4%) or in health facility records (5.6%). Logistic regression and survival analysis were used to assess factors associated with vaccination status and age at vaccination. Receipt of pentavalent vaccine by age 15 weeks was associated with rotavirus vaccination (OR: 5.1; 95% CI 2.7, 9.4), and receipt of the second pentavalent dose by age 32 weeks was associated with receipt of two rotavirus vaccine doses (OR: 5.0; 95% CI 2.1-12.3). Timely coverage with the first pentavalent vaccine dose was 88.2% in the 2007 cohort and 91.1% in the 2008 cohort (p=0.04). Children born in 2009, when a four-month national rotavirus vaccine stock-out occurred, had an older median age of receipt of rotavirus vaccine and were less likely to receive rotavirus on the same date as the same dose of pentavalent vaccine than children born in 2007 and 2008. Upper age limit recommendations for rotavirus vaccine administration contributed to suboptimal vaccination coverage. Survey data suggest that late rotavirus vaccination and co administration with later doses of pentavalent vaccine among children born in 2009 helped increase rotavirus vaccine coverage following shortages. PMID- 26263201 TI - Mapping T and B cell epitopes in sperm protein 17 to support the development of an ovarian cancer vaccine. AB - Ovarian cancer (OC) is the seventh most common cancer in women worldwide, and the leading cause of death from gynaecological malignancy. Immunotherapeutic strategies including cancer vaccines are considered less toxic and more specific than current treatments. Sperm surface protein (Sp17) is a protein aberrantly expressed in primary as well as in metastatic lesions in >83% of ovarian cancer patients. Vaccines based on the Sp17 protein are immunogenic and protective in animal models. To map the immunogenic regions and support the development of human Sp17 peptide based vaccines, we used 6 overlapping peptides of the human Sp17 sequence adjuvanted with CpG to immunise humanised HLA-A2.1 transgenic C57BL/6 mice, and assessed immunogenicity by ELISPOT and ELISA. No CD8 T cells were found to be induced to a comprehensive panel of 10 HLA-A2.1 or H-2K(b) binding predicted epitopes. However, one of the 6 peptides, hSp17111-142, induced high levels of antibodies and IFN-gamma producing T cells (but not IL-17 or IL-4) both in C57BL/6 and in C57BL/6-HLA-A2.1 transgenic mice. C57BL/6 mice immunised with CpG adjuvanted hSp17111-142 significantly prolonged the life-span of the mice bearing the ovarian carcinoma ID8 cell line. We further mapped the immuno dominant B and T cell epitope regions within hSp17111-142 using ELISPOT and competition ELISA. Herein, we report the identification of a single immuno dominant B cell (134-142 aa) epitope and 2 T helper 1 (Th1) cell epitopes (111 124 aa and 124-138 aa). These result together support further exploration of hSp17111-142 peptide formulations as vaccines against ovarian cancer. PMID- 26263202 TI - Binocular versus standard occlusion or blurring treatment for unilateral amblyopia in children aged three to eight years. AB - BACKGROUND: Current treatments for amblyopia in children, occlusion and pharmacological blurring, have had limited success, with less than two-thirds of children achieving good visual acuity of at least 0.20 logMAR in the amblyopic eye, limited improvement of stereopsis, and poor compliance. A new treatment approach, based on the dichoptic presentation of movies or computer games (images presented separately to each eye), may yield better results, as it aims to balance the input of visual information from each eye to the brain. Compliance may also improve with these more child-friendly treatment procedures. OBJECTIVES: To determine whether binocular treatments in children aged three to eight years with unilateral amblyopia result in better visual outcomes than conventional occlusion or pharmacological blurring treatment. SEARCH METHODS: We searched the Cochrane Eyes and Vision Group Trials Register (last date of searches: 14 April 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to April 2015), EMBASE (January 1980 to April 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. SELECTION CRITERIA: Two review authors independently screened the results of the search in order to identify studies that met the inclusion criteria of the review: randomised controlled trials (RCTs) that enrolled participants between the ages of three and eight years old with unilateral amblyopia, defined as best-corrected visual acuity (BCVA) worse than 0.200 logMAR in the amblyopic eye, and BCVA 0.200 logMAR or better in the fellow eye, in the presence of an amblyogenic risk factor such as anisometropia, strabismus, or both. Prior to enrolment, participants were to have undergone a cycloplegic refraction and comprehensive ophthalmic examination including fundal examination. In addition, participants had to have completed a period of optical treatment, if indicated, and BCVA in the amblyopic eye had to remain unchanged on two consecutive assessments despite reportedly good compliance with glasses wearing. Participants were not to have received any treatment other than optical treatment prior to enrolment. We planned to include any type of binocular viewing intervention; these could be delivered on different devices including computer monitors viewed with LCD shutter glasses or hand-held screens including mobile phone screens with lenticular prism overlay. Control groups were to have received standard amblyopia treatment; this could include occlusion or pharmacological blurring of the better-seeing eye. We planned to include full-time (all waking hours) and part-time (between 1 and 12 hours a day) occlusion regimens. DATA COLLECTION AND ANALYSIS: We planned to use standard methodological procedures expected by The Cochrane Collaboration. We had planned to meta-analyse the primary outcome, that is mean distance BCVA in the amblyopic eye at 12 months after the cessation of treatment. MAIN RESULTS: We could identify no RCTs in this subject area. AUTHORS' CONCLUSIONS: Further research is required to allow decisions about implementation of binocular treatments for amblyopia in clinical practice. Currently there are no clinical trials offering standardised evidence of the safety and effectiveness of binocular treatments, but results from non controlled cohort studies are encouraging. Future research should be conducted in the form of RCTs, using acknowledged methods of visual acuity and stereoacuity assessment with known reproducibility. Other important outcome measures include outcomes reported by users, compliance with treatment, and recurrence of amblyopia after cessation of treatment. PMID- 26263203 TI - [The psychiatric association accepts antroposophical homeopathy]. PMID- 26263204 TI - [The Medical Products Agency's referral is about patient safety]. PMID- 26263205 TI - [Well-planned excisions--and cookies]. PMID- 26263207 TI - Developing Brain Injury Interventions on Both Ends of the Treatment Continuum Depends Upon Early Research Partnerships and Feasibility Studies. AB - PURPOSE: The purpose of this research article is to describe two very different lines of brain injury treatment research, both of which illuminate the benefits of implementation science. METHOD: The article first describes the development and pilot of a computerized cognitive intervention and highlights how adherence to implementation science principles improved the design of the intervention. Second, the article describes the application of implementation science to the development of assistive technology for cognition. RESULTS: The Consolidated Framework for Implementation Research (CFIR; Damschroder et al., 2009) and the menu of implementation research strategies by Powell et al. (2012) provide a roadmap for cognitive rehabilitation researchers to attend to factors in the implementation climate that can improve the development, usability, and adoptability of new treatment methods. CONCLUSION: Attention to implementation science research principles has increased the feasibility and efficacy of both impairment-based cognitive rehabilitation programs and assistive technology for cognition. PMID- 26263206 TI - Nbs1 ChIP-Seq Identifies Off-Target DNA Double-Strand Breaks Induced by AID in Activated Splenic B Cells. AB - Activation-induced cytidine deaminase (AID) is required for initiation of Ig class switch recombination (CSR) and somatic hypermutation (SHM) of antibody genes during immune responses. AID has also been shown to induce chromosomal translocations, mutations, and DNA double-strand breaks (DSBs) involving non-Ig genes in activated B cells. To determine what makes a DNA site a target for AID induced DSBs, we identify off-target DSBs induced by AID by performing chromatin immunoprecipitation (ChIP) for Nbs1, a protein that binds DSBs, followed by deep sequencing (ChIP-Seq). We detect and characterize hundreds of off-target AID dependent DSBs. Two types of tandem repeats are highly enriched within the Nbs1 binding sites: long CA repeats, which can form Z-DNA, and tandem pentamers containing the AID target hotspot WGCW. These tandem repeats are not nearly as enriched at AID-independent DSBs, which we also identified. Msh2, a component of the mismatch repair pathway and important for genome stability, increases off target DSBs, similar to its effect on Ig switch region DSBs, which are required intermediates during CSR. Most of the off-target DSBs are two-ended, consistent with generation during G1 phase, similar to DSBs in Ig switch regions. However, a minority are one-ended, presumably due to conversion of single-strand breaks to DSBs during replication. One-ended DSBs are repaired by processes involving homologous recombination, including break-induced replication repair, which can lead to genome instability. Off-target DSBs, especially those present during S phase, can lead to chromosomal translocations, deletions and gene amplifications, resulting in the high frequency of B cell lymphomas derived from cells that express or have expressed AID. PMID- 26263208 TI - Facile synthesis of partially uncapped liposomes. AB - Sophisticated control of the assembly of nano-sized structures to achieve desired properties is one of the most efficient techniques in drug carrier design. In this study, we hypothesized that under magnetic shear stress, high-density superparamagnetic Fe3O4 nanoparticles dispersed in a liposome would apply a high load in a particular direction to a liposome membrane and ultimately generate open lipid bilayer holes. Indeed, the designed experimental conditions enabled the formation of one or multiple open pore sites in liposome membranes. With this evidence, open lipid bilayer holes in liposome membranes were further used as open entrances for proteins (bovine serum albumin or insulin) into the liposomes prior to the natural recovery (i.e., closing) of the lipid bilayer holes. This trial will provide potential opportunities for the engineering of functional liposomes for protein drug delivery. PMID- 26263209 TI - Transdermal treatment of the surgical and burned wound skin via phytochemical capped gold nanoparticles. AB - The biological activities and therapeutic potential of phytochemical-decorated Au nanoparticles (Phyto-AuNPs) were investigated through the treatment of Phyto AuNPs on the dorsal skin of rats via transdermal drug delivery process in order to regenerate surgical wounded and burned skin. Two different Phyto-AuNPs were applied to the dorsal skin: gallic acid-isoflavone--covered AuNPs (GI-AuNPs) and protocatechuic acid-isoflavone--covered AuNPs (PI-AuNPs). From the biological activity monitoring, it has been resulted that 5-fold thicker epidermis (ER), 50% reduction of metalloproteinase-1 (MMP-1) level, 3-fold higher superoxide dismutase (SOD) activity were obtained in the Phyto-AuNP-treated group, compared with a vehicle group (deionized water (DI-water) treatment). Moreover, the Phyto AuNPs treatment on the surgical and burn damaged Sprague-Dawley (SD) rats induced higher expression of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2). It would be plausible that antioxidant property of Phyto-AuNPs assist the acceleration and activation of biomolecules in the healing mechanism, where Phyto-AuNPs can be potential candidates for skin regeneration and wound healing. PMID- 26263210 TI - Starch-based Pickering emulsions for topical drug delivery: A QbD approach. AB - Pickering emulsions are stabilized by solid particles instead of surfactants and have been widely investigated in pharmaceutical and cosmetic fields since they present less adverse effects than the classical emulsions. A quality by design (QbD) approach was applied to the production of w/o emulsions stabilized by starch. A screening design was conducted to identify the critical variables of the formula and the process affecting the critical quality properties of the emulsion (droplet size distribution). The optimization was made by establishing the Design Space, adjusting the concentration of starch and the quantity of the internal aqueous phase. The emulsion production process was, in turn, adjusted by varying the time and speed of stirring, to ensure quality and minimum variability. The stability was also investigated, demonstrating that an increase in starch concentration improves the stability of the emulsion. Rheological and mechanical studies indicated that the viscosity of the emulsions was enhanced by the addition of starch and, to a higher extent, by the presence of different lipids. The developed formulations was considered non-irritant, by an in vitro assay using human cells from skin (Df and HaCat) with the cell viability higher than 90% and, with self-preserving properties. Finally, the QbD approach successfully built quality in Pickering emulsions, allowing the development of hydrophilic drug-loaded emulsions stabilized by starch with desired organoleptic and structural characteristics. The results obtained suggest that these systems are a promising vehicle to be used in products for topical administration. PMID- 26263211 TI - Femtomolar oligonucleotide detection by a one-step gold nanoparticle-based assay. AB - A sequence-specific oligonucleotide detection method based on the tail-to-tail aggregation of functionalized gold nanoparticles in the presence of target analytes is presented together with its optimization and capabilities for detection of single nucleotide polymorphisms (SNPs). In this single-step method, capture probes are freely accessible for hybridization, resulting in an improved assay performance compared to substrate-based assays. The analytes bring the nanoparticles close to each other via hybridization, causing a red shift of the nanoparticle plasmon peak detected by a spectrophotometer or CCD camera coupled to a darkfield imaging system. Optimal conditions for the assay were found to be (i) use of capture probes complementary to the target without any gap, (ii) maximum possible probe density on the gold nanoparticles, and (iii) 1M ionic strength buffer. The optimized assay has a 1 fM limit of detection and fM to 10 pM dynamic range, with detection of perfect match sequences being three orders of magnitude more sensitive than targets with single nucleotide mismatches. PMID- 26263212 TI - Photoluminescent PEG based comacromers as excitation dependent fluorophores for biomedical applications. AB - We report a novel multi-modal biodegradable photoluminescent comacromer [poly(propylene fumarate)-PEG-glycine] (PLM) having excitation-dependent fluorescence (EDF) for biomedical applications. The photoluminescence of the synthesized PLM in aqueous and solid state condition, fluorescence life time and photo stability were evaluated. Hydrogels and nanogels were prepared from the PLM by cross linking with acrylic acid. Nanogels exhibited spherical morphology with a particle size of 100 nm as evaluated by transmission electron microscopy (TEM). In vitro cytotoxic and hemolytic studies revealed cytocompatibility. Furthermore, cellular imaging of nanogels on L929 fibroblast and Hela cell lines revealed EDF characteristics. We hypothesize that the EDF characteristics of the synthesized PLM may be attributed to the presence of n-pi* interactions of the hydroxyl oxygen atoms of PEG with carbonyl groups of the ester linkages. Taken together, our results indicate that the synthesized PEG-based comacromer can serve as biocompatible fluorophores for various biomedical applications. More importantly, the facile way of synthesizing fluorescent polymers based on PEG with EDF characteristics demonstrated in this work can pave the way for developing more novel biocompatible fluorophores with wide range of biomedical applications. PMID- 26263213 TI - Preparation of self-assembled core-shell nano structure of conjugated generation 4.5 poly (amidoamine) dendrimer and monoclonal Anti-IL-6 antibody as bioimaging probe. AB - In this article, interleukin-6 (IL-6)-conjugated anionic generation 4.5 (G4.5) poly(amidoamine) (PAMAM) was synthesized through EDC/NHS coupling chemistry and evaluated for its optical properties in vitro. Conjugation was confirmed using Fourier-transformed infrared spectroscopy (FT-IR) and 2-dimensional nuclear magnetic resonance (2D NMR). After IL-6 conjugation, nanoparticle size increased to approximately 70 nm and zeta potential increased from -56.5 +/- 0.2 to -19.1 +/- 2.4 mV due to neutralization of negatively charged G4.5. Wide-angle X-ray scattering (WAXS) suggested that a layered nanoparticle structure was formed by the G4.5/IL-6 conjugate. Most interestingly, the intrinsic fluorescence of G4.5 significantly increased after IL-6 conjugation and underwent a blue shift as a result of H-aggregation. Furthermore, the cellular uptake of the conjugates by HeLa cells was significantly enhanced in comparison to free G4.5, as demonstrated by confocal microscopy and flow cytometry. These results indicated that the described system may be a potential bioimaging probe in vitro. PMID- 26263214 TI - Probing the binding of trypsin to glutathione-stabilized gold nanoparticles in aqueous solution. AB - We investigate the interaction of trypsin with glutathione-stabilized Au nanoparticles (NPs) using fluorescence, synchronous fluorescence and ultraviolet (UV) absorption spectroscopy. We find that trypsin binds strongly to the Au NPs with a static quenching mechanism, and that the interaction is characteristic of positive cooperative binding. Furthermore, we determine the binding constants and the thermodynamic parameters, which suggest that the main binding forces between the glutathione-stabilized Au NPs and trypsin are electrostatic interactions and hydrogen bonding. Analysis of UV-vis absorption spectra suggests that aggregation of the Au NPs occurs in the trypsin/Au NPs system, which significantly alters the conformation of the protein. PMID- 26263215 TI - Water structure at the interfaces between a zwitterionic self-assembled monolayer/liquid water evaluated by sum-frequency generation spectroscopy. AB - A silane coupling agent having a zwitterionic end group was covalently bound to a semi-cylindrical fused silica prism for sum-frequency generation (SFG) analyses and to a flat glass for estimating biological affinity. It was found that total intensity of the -derived from water in contact with a positively or negatively charged SAM-modified surface and a bare silica prism. These results indicated that water molecules in the vicinity of the zwitterionic SAM-modified surface are not strongly oriented in comparison with those of lopsidedly charged SAMs and bare silica. Moreover, the zwitterionic SAM surface suppressed non-specific adsorption of bovine serum albumin in contrast to the significant adsorption to lopsidedly charged SAMs and the bare cover glass. On the other hand, fibroblasts gradually adhered to the SAM surfaces and extended regardless of the electrical charge of the SAM, though the number of cells that adhered to the zwitterionic SAM was the smallest. The results strongly suggested that the charge neutralization of a solid material surface is very important for anti-biofouling properties. PMID- 26263217 TI - Micellar carriers for the delivery of multiple therapeutic agents. AB - Multi-drug therapy is described as a simultaneous or sequential administration of two or more drugs with similar or different mechanisms of action and is recognized as a more efficient solution to combat successfully, various ailments. Polymeric micelles (PMs) are self-assemblies of block copolymers providing numerous opportunities for drug delivery. To date various micellar formulations were studied for delivery of drugs, nutraceuticals and genes; a few of them are in clinical trials. It was observed that there is an immense need for the development of PMs embedding multiple therapeutic agents to combat various ailments, including cancers, HIV/AIDS, malaria, multiple sclerosis, hypertension, infectious diseases, cardiovascular and metabolic diseases, immune disorders and many psychiatric disorders. Several combinations of drug-drug, drug nutraceutical, drug-gene and drug-siRNA explored to date are detailed in this review, with a special emphasis on their potential and future perspectives. A summary of various preparation methods, characterization techniques and applications of PMs are also provided. This review presents a holistic approach on multi-drug delivery using micellar carriers and emphasizes on the development of therapeutic hybrids embedding novel combinations for safer and effective therapy. PMID- 26263218 TI - Robust fluorescence sensing platform for detection of CD44 cells based on graphene oxide/gold nanoparticles. AB - Gold-coated graphene oxide hybrid material (GO/AuNPs) has exceptional physical and chemical properties like pi-pi stacking interaction and plays a role in quencher of fluorescence dye. Therefore, GO/AuNPs could enhance the signal-to background ratio with fluorescence dye that was the point in this fluorescent biosensor. In this study, tetramethyl-6-carboxy-rhodamine (TAMRA)-labeled aptamers that specifically interact with the hyaluronic acid binding domain of CD44 were used as targets to investigate the applicability of the method. GO/AuNPs-TAMRA-aptamer complexes could detect CD44 target cancer cells within a concentration range of 1 * 10(1) to 1 * 10(7) CFU/mL. A linear relationship was observed between target cell concentration and relative fluorescence intensity. The more mounted up CD44 target cell concentrations, relative fluorescence intensity of GO/AuNPs-TAMRA-aptamer complexes was increased even more, which was superior to that of GO alone. Sensitivity of the detection system displayed a low detection limit of 1 * 10(1) CFU/mL. Additionally, this method is specific in that fluorescence is not much enhanced in CD44 negative cancer cell line. Thus, the fluorescence sensing based on GO/AuNPs could be developed to receptive and robust detection tool for various target molecules. PMID- 26263216 TI - Non-covalent complexes of folic acid and oleic acid conjugated polyethylenimine: An efficient vehicle for antisense oligonucleotide delivery. AB - Polyethylenimine (PEI) was conjugated to oleic acid (PEI-OA) and evaluated as a delivery agent for LOR-2501, an antisense oligonucleotide against ribonucleotide reductase R1 subunit. PEI-OA/LOR-2501 complexes were further coated with folic acid (FA/PEI-OA/LOR-2501) and evaluated in tumor cells. The level of cellular uptake of FA/PEI-OA/LOR-2501 was more than double that of PEI/LOR-2501 complexes, and was not affected by the expression level of folate receptor (FR) on the cell surface. Efficient delivery was seen in several cell lines. Furthermore, pathway specific cellular internalization inhibitors and markers were used to reveal the principal mechanism of cellular uptake. FA/PEI-OA/LOR-2501 significantly induced the downregulation of R1 mRNA and R1 protein. This novel formulation of FA/PEI-OA provides a reliable and highly efficient method for delivery of oligonucleotide and warrants further investigation. PMID- 26263219 TI - Structure, molecular simulation, and release of aspirin from intercalated Zn-Al layered double hydroxides. AB - Aspirin or acetylsalicylic acid (AA), a non-steroidal anti-inflammatory drug, is intercalated into Zn-Al-layered double hydroxides (ZnAl-LDHs) by co-precipitation and reconstruction methods. The composition, structure, and morphology of the intercalated products as well as their release behavior are determined experimentally and theoretically by Material Studio 5.5. Experimental results disclose the strong interaction between the LDHs sheets and AA in the intercalated ZnAl-LDHs produced by co-precipitation and slow release of AA from the intercalated ZnAl-LDHs in both phosphate buffered saline (PBS) and borate buffered saline (BBS) solutions. The percentage of AA released from the ZnAl-LDHs prepared by both methods in PBS (96.87% and 98.12%) are much more than those in BBS (68.59% and 81.22%) implying that both H4BO4(-) and H2PO4(-) can exchange with AA in the ZnAl-LDHs. After AA is released to PBS, ZnAl-LDHs break into small pieces. The experimental results are explained theoretically based on the calculation of the bonding energy between the anions and LDHs sheets as well as the AlO bond length change in the LDHs sheets. PMID- 26263220 TI - Reversibility of the interactions between a novel surfactant derived from lysine and biomolecules. AB - In this work the novel cationic surfactant derived from lysine (S)-5-acetamido-6 (dodecylamino)-N,N,N-trimethyl-6-oxohexan-1-ammonium chloride, LYCl, was prepared and the physicochemical characterization of its aqueous solutions was carried out. The binding of LYCl to bovine serum albumin, BSA, and to double stranded calf thymus DNA, ctDNA, was investigated using several techniques. Results show that LYCl binding to BSA is followed by a decrease in the alpha-helix content caused by the unfolding of the protein. LYCl association to ctDNA mainly occurs through groove binding and electrostatic interactions. These interactions cause morphological changes in the polynucleotide from an elongated coil structure to a more compact globular structure, resulting in the compaction of ctDNA. Addition of beta-cyclodextrin, beta-CD, to the BSA-LYCl and ctDNA-LYCl complexes is followed by the refolding of BSA and the decompaction of ctDNA. This can be explained by the ability of beta-CD to hinder BSA-LYCl and ctDNA-LYCl interactions due to the stronger and more specific beta-CD-LYCl hydrophobic interactions. The stoichiometry of the beta-CD:LYCl inclusion complex and its formation equilibrium constant were determined in this work. The reported procedure using beta-CD is an efficient way to refold proteins and to decompact DNA, after the morphological changes caused in the biomolecules by their interaction with cationic surfactants. PMID- 26263221 TI - Simultaneous encapsulation of magnetic nanoparticles and zinc phthalocyanine in poly(methyl methacrylate) nanoparticles by miniemulsion polymerization and in vitro studies. AB - The aim of this work was the simultaneous encapsulation of magnetic nanoparticles (MNPs) and zinc(II) phthalocyanine (ZnPc) in poly(methyl methacrylate) (PMMA) (MNPsZnPc-PMMA) nanoparticles (NPs) by miniemulsion polymerization and to evaluate the photobiological activity and/or hyperthermia (HPT) against human glioblastoma cells (U87MG). MNPsZnPc-PMMA NPs presented an average diameter of 104 +/- 2.5 nm with a polydispersity index (PdI) of 0.14 +/- 0.03 and negative surface charge - 47 +/- 2.2 mV (pH 7.4 +/- 0.1). The encapsulation efficiency (EE%) of ZnPc was 85.7% +/- 1.30. The release of ZnPc from PMMA NPs was slow and sustained without the presence of burst effect, indicating a homogeneous distribution of the drug in the polymeric matrix. In the biological assay, MNPsZnPc-PMMA NPs showed considerable cytotoxic effect on U87MG cells only after activation with visible light at 675 nm (photodynamic therapy, PDT) or after application of an alternating magnetic field. The simultaneous encapsulation of MNPs and ZnPc in a drug delivery system with sustained release can be a new alternative for cancer treatment leading to significant tumor regression after minimum doses of heat dissipation and light. PMID- 26263222 TI - Preparation of photoreactive phospholipid polymer nanoparticles to immobilize and release protein by photoirradiation. AB - Photoreactive and cytocompatible polymer nanoparticles for immobilizing and releasing proteins were prepared. A water-soluble and amphiphilic phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate (BMA)-co-4-(4-(1-methacryloyloxyethyl)-2-methoxy-5-nitrophenoxy) butyric acid (PL)) (PMB-PL) was synthesized. The PMB-PL underwent a cleavage reaction at the PL unit with photoirradiation at a wavelength of 365 nm. Additionally, the PMB-PL took polymer aggregate in aqueous medium and was used to modify the surface of biodegradable poly(L-lactic acid) (PLA) nanoparticle as an emulsifier. The morphology of the PMB-PL/PLA nanoparticle was spherical and approximately 130 nm in diameter. The carboxylic acid group in the PL unit could immobilize proteins by covalent bonding. The bound proteins were released by a photoinduced cleavage reaction. Within 60s, up to 90% of the immobilized proteins was released by photoirradiation. From these results and with an understanding of the fundamental properties of MPC polymers, we concluded that PMB-PL/PLA nanoparticles have the potential to be used as smart carriers to deliver proteins to biological systems, such as the inside of living cells. PMID- 26263224 TI - Emotion, philosophical issues about. AB - We start this overview by discussing the place of emotions within the broader affective domain-how different are emotions from moods, sensations, and affective dispositions? Next, we examine the way emotions relate to their objects, emphasizing in the process their intimate relations to values. We move from this inquiry into the nature of emotion to an inquiry into their epistemology. Do they provide reasons for evaluative judgments and, more generally, do they contribute to our knowledge of values? We then address the question of the social dimension of emotions, explaining how the traditional nature versus nurture contrast applies to them. We finish by exploring the relations between emotions, motivation and action, concluding this overview with a more specific focus on how these relations bear on some central ethical issues. PMID- 26263223 TI - The Relationships of Obesity-Related Genetic Variants With Metabolic Profiles and Response to Metformin in Clozapine-Treated Patients With Schizophrenia. AB - Obesity-related genetic variants, including TMEM18 (rs6548238), SH2B1 (rs7498665), and GNPDA2 (rs10938397), have been shown to be associated with obesity in the general population. Our study aimed to test whether these genetic variants are associated with metabolic profiles and metformin treatment response in clozapine-treated schizophrenic patients. We recruited 107 clozapine-treated patients who were genotyped and measured their metabolic profiles. Fifty-five subjects, who had at least 1 metabolic abnormality in a range of measures, were subsequently randomized to a 24-week trial of metformin (n = 28) or placebo (n = 27). We examined the associations between TMEM18, SH2B1, GNPDA2 genetic variants and metabolic profiles at baseline in all patients and metabolic changes in the trial groups. We found a significant association between SH2B1 and blood pressure at baseline in all patients. In the metformin group, TMEM18 minor allele carriers had a greater reduction in insulin levels (P = 0.04). A significantly higher proportion of TMEM18 and GNPDA2 minor allele carriers (60% and 40%) lost more than 7% of their body weight after metformin treatment as compared with their homozygous counterparts (21.7% and 15.4%, P = 0.02 and 0.004, respectively).There were trends toward favorable metabolic changes in minor allele carrier groups. In the placebo group, no association between genetic variants and changes in metabolic profiles was found. In conclusion, the study results suggest that these genes might be associated with metabolic abnormalities and response to metformin in clozapine-treated patients with schizophrenia. PMID- 26263225 TI - Human collective reactions to threat. AB - A common assumption regarding mass emergency situations is that individuals in such contexts behave in a way that maximizes their likelihood to escape, at the expense, or with little concern for, the welfare and survival of their neighbors. Doing so, they might even compromise the effectiveness of group evacuation. This conception follows the views of early works on crowd psychology, a tradition born with Gustave Le Bon's The Crowd: a study of the Popular Mind, first published in 1895, and which has had a tremendous impact on scientific representations of people's behavior in mass emergency contexts. Indeed, this work has greatly contributed to the idea that, in such situations, people revert to a primitive, impulsive, irrational, and antisocial nature, causing the breakdown of social order. However, more empirically oriented studies have consistently reported little collective panic, as well as a great deal of solidarity and pro-social behavior during mass emergency situations. Because of institutional barriers, such views have remained largely unknown to cognitive psychologists. Yet these are important results in that they show that human individual and collective reactions to threat are primarily affiliative. Indeed, far from leading to the breakdown of the social fabrics, the presence of a common threat can strengthen social bonds. PMID- 26263226 TI - Educational neuroscience: definitional, methodological, and interpretive issues. AB - In this study, we hope to accomplish three aims as follows: (1) provide greater clarity regarding the nature and scope of the field of educational neuroscience, (2) propose a framework for understanding when and how neuroscientific research could be informative for educational practice, and (3) describe some examples of neuroscientific findings from the domains of reading and mathematics that are informative according to this framework. We propose that psychological models of learning-related processes should be the basis of instructional decisions, and that neuroscientific evidence in combination with traditional evidence from psychological experiments should be used to decide among competing psychological models. Our review of the neuroscientific evidence for both reading and mathematics suggests that while much has been learned over the past 20 years, there is still a 'disconnect' between contemporary psychological models that emphasize higher level skills and neuroscientific studies that focus on lower level skills. Moreover, few researchers have used neuroscientific evidence to decide among psychological models, but have focused instead on identifying the brain regions that subtend component skills of reading and math. Nevertheless, neuroscientific studies have confirmed the intrinsic relationship between reading and spoken language, revealed interesting predictive relationships between anatomical structures and reading and math disabilities, and there is the potential for fruitful collaborations between neuroscientists and psychologists in the future. PMID- 26263227 TI - Connectionist perspectives on language learning, representation and processing. AB - The field of formal linguistics was founded on the premise that language is mentally represented as a deterministic symbolic grammar. While this approach has captured many important characteristics of the world's languages, it has also led to a tendency to focus theoretical questions on the correct formalization of grammatical rules while also de-emphasizing the role of learning and statistics in language development and processing. In this review we present a different approach to language research that has emerged from the parallel distributed processing or 'connectionist' enterprise. In the connectionist framework, mental operations are studied by simulating learning and processing within networks of artificial neurons. With that in mind, we discuss recent progress in connectionist models of auditory word recognition, reading, morphology, and syntactic processing. We argue that connectionist models can capture many important characteristics of how language is learned, represented, and processed, as well as providing new insights about the source of these behavioral patterns. Just as importantly, the networks naturally capture irregular (non-rule-like) patterns that are common within languages, something that has been difficult to reconcile with rule-based accounts of language without positing separate mechanisms for rules and exceptions. PMID- 26263228 TI - Pretend play. AB - Pretend play is a form of playful behavior that involves nonliteral action. Although on the surface this activity appears to be merely for fun, recent research has discovered that children's pretend play has connections to important cognitive and social skills, such as symbolic thinking, theory of mind, and counterfactual reasoning. The current article first defines pretend play and then reviews the arguments and evidence for these three connections. Pretend play has a nonliteral correspondence to reality, hence pretending may provide children with practice with navigating symbolic relationships, which may strengthen their language skills. Pretend play and theory of mind reasoning share a focus on others' mental states in order to correctly interpret their behavior, hence pretending and theory of mind may be mutually supportive in development. Pretend play and counterfactual reasoning both involve representing nonreal states of affairs, hence pretending may facilitate children's counterfactual abilities. These connections make pretend play an important phenomenon in cognitive science: Studying children's pretend play can provide insight into these other abilities and their developmental trajectories, and thereby into human cognitive architecture and its development. PMID- 26263230 TI - Avian cognition: examples of sophisticated capabilities in space and song. AB - Although birds have traditionally and colloquially been considered less cognitively complex than mammals, and especially primates, more recent research has consistently refuted these assumptions. We argue that the impressive abilities of birds to navigate and communicate require considerable information processing capabilities. These capacities include collecting, organizing, and selecting from a wide variety of navigational cues to orient toward and find a goal location in the spatial domain, and utilizing open-ended categorization and possibly even abstract reasoning to discriminate species-specific acoustic features of songs and calls. Furthermore, these abilities may be present across many avian species, providing evidence for domain-general cognitive facilities. We provide examples of processes in spatial learning and communication in birds, and locate them within the general literature, as evidence that the term 'bird brain' should not be considered a pejorative. PMID- 26263231 TI - Human kin detection. AB - Natural selection has favored the evolution of behaviors that benefit not only one's genes, but also their copies in genetically related individuals. These behaviors include optimal outbreeding (choosing a mate that is neither too closely related, nor too distant), nepotism (helping kin), and spite (hurting non kin at a personal cost), and all require some form of kin detection or kin recognition. Yet, kinship cannot be assessed directly; human kin detection relies on heuristic cues that take into account individuals' context (whether they were reared by our mother, or grew up in our home, or were given birth by our spouse), appearance (whether they smell or look like us), and ability to arouse certain feelings (whether we feel emotionally close to them). The uncertainties of kin detection, along with its dependence on social information, create ample opportunities for the evolution of deception and self-deception. For example, babies carry no unequivocal stamp of their biological father, but across cultures they are passionately claimed to resemble their mother's spouse; to the same effect, 'neutral' observers are greatly influenced by belief in relatedness when judging resemblance between strangers. Still, paternity uncertainty profoundly shapes human relationships, reducing not only the investment contributed by paternal versus maternal kin, but also prosocial behavior between individuals who are related through one or more males rather than females alone. Because of its relevance to racial discrimination and political preferences, the evolutionary pressure to prefer kin to non-kin has a manifold influence on society at large. PMID- 26263232 TI - Linguistic capacity of non-human animals. AB - Linguists interested in language evolution tend to focus on combinatorial features and rightly point out the lack of comparable evidence in animal communication. However, human language is based on various unique capacities, such as a motor capacity of sophisticated vocal control and a cognitive capacity of acting on others' psychological states. These features are only present in very rudimentary forms in non-human primates, suggesting they have evolved more recently in the human lineage. Here, the evidence from recent fieldwork for precursors of these abilities is reviewed, notably sequence-based semantic communication, vocal tract control, and audience awareness. Overall, there is evidence for both continuity and discontinuity when comparing modern primate and human communication, suggesting that the origin of language is the result of multiple gradual transitions from earlier forms of primate-like communication and social cognition, rather than a sudden and fundamental redesign in ancestral human communication and cognition. PMID- 26263229 TI - fNIRS in the developmental sciences. AB - With the introduction of functional near-infrared spectroscopy (fNIRS) into the experimental setting, developmental scientists have, for the first time, the capacity to investigate the functional activation of the infant brain in awake, engaged participants. The advantages of fNIRS clearly outweigh the limitations, and a description of how this technology is implemented in infant populations is provided. Most fNIRS research falls into one of three content domains: object processing, processing of biologically and socially relevant information, and language development. Within these domains, there are ongoing debates about the origins and development of human knowledge, making early neuroimaging particularly advantageous. The use of fNIRS has allowed investigators to begin to identify the localization of early object, social, and linguistic knowledge in the immature brain and the ways in which this changes with time and experience. In addition, there is a small but growing body of research that provides insight into the neural mechanisms that support and facilitate learning during the first year of life. At the same time, as with any emerging field, there are limitations to the conclusions that can be drawn on the basis of current findings. We offer suggestions as to how to optimize the use of this technology to answer questions of theoretical and practical importance to developmental scientists. PMID- 26263233 TI - The evolutionary diagnosis of mental disorder. AB - Medicalization of human behavioral diversity is a recurrent theme in the history of psychiatry, and the problem of defining what is a genuine mental disorder is an unresolved question since the origins of clinical psychopathology. Darwinian psychiatry can formulate a definition of mental disorder that is value free and based on factual criteria. From an evolutionary perspective, genuine mental disorders are maladaptive conditions. The ultimate function of an adaptation is gene propagation via maximization of survival and reproduction. It follows that a distressing and/or disabling psychological or behavioral syndrome is a psychiatric disorder only if it impacts negatively on the individual's inclusive fitness. However, in many cases, an evolutionary definition of disorder cannot be reconciled with current social values. Thus, clinicians adopting the evolutionary approach should conform to the prevailing trend of contemporary medicine and accept that their task is to be healers of the distressed, not watchdogs of biological adaptation. These pragmatic considerations do not minimize the scientific validity of the Darwinian definition of mental disorders. Probably, its major contribution to psychiatric theory is the elimination of the necessity to find a brain lesion or dysfunctional mechanism to validate the distinction between disorders and non-disorders. PMID- 26263235 TI - Impact of Infectious Diseases Team Consultation on Antimicrobial Use, Length of Stay and Mortality. AB - BACKGROUND: Infectious disease (ID) clinicians and multidisciplinary teams may have a beneficial impact on patient outcomes. This study was conducted to determine the impact of dedicated ID team rounding in an adult noncardiac intensive care unit (ICU) on antimicrobial costs, length of stay and mortality. METHODS: The authors instituted dedicated ICU ID team rounds at a large tertiary care hospital ICU ("intervention"), with the ID team conducting rounds in the ICU every weekday. The authors compared the cost of antimicrobial agents, total hospital and ICU length of stay and inpatient mortality for the 6-month period before and after institution of these rounds between those seen versus those not seen by the ID team. RESULTS: Among 386 patients analyzed, 206 were admitted in the preintervention and 180 in the postintervention period. Among those seen by the ID team, there was an 18% decrease in total antimicrobial cost (P < 0.0001), 40% decrease in ICU length of stay (P = 0.1), 33% decrease in overall hospital length of stay (P = 0.03) and 34% decrease in mortality (0.04) from preintervention to postintervention period. Among those not seen by ID, there was a 39% decrease in cost among those not seen by ID (P < 0.0001), but length of ICU or hospital stay and mortality were not significantly different. CONCLUSIONS: Institution of dedicated ID team rounding in the ICU leads to substantial decreases in antimicrobial costs, hospital length of stay and inpatient mortality among those patients seen by the team. PMID- 26263236 TI - Comparison of Self-Rated Health Among Latina Immigrants in a Southern U.S. City and a National Sample. AB - BACKGROUND: In the United States, Latinos often report fair/poor self-rated health, which is an indicator for increased morbidity and mortality. Foreign-born Latinos in new immigrant destinations, such as the south, may rate their health more poorly than their counterparts elsewhere in the United States, because of the factors associated with migration and settlement in these communities. METHODS: The authors assessed foreign-born Latinas' self-rated health in Birmingham, Alabama (n = 765), and compared it with that of foreign-born Latinas in the National Health Interview Survey (NHIS; n = 8,746). Birmingham participants were matched to Latinas in the NHIS using propensity scores. The authors examined factors associated with reporting worse health using ordered logistic regression and inverse probability of treatment weights. RESULTS: After propensity score matching, 47.6% of foreign-born Latinas in the Birmingham study reported their health as fair/poor compared with 17.9% of foreign-born Latinas in the NHIS (P < 0.001). The association between being Mexican born versus from other countries with poorer health was stronger in the Birmingham study (odds ratio: 4.46 [95% CI: 1.91-10.4]) than in the NHIS (odds ratio: 1.09 [95% CI: 1.08 1.09]). Shorter durations of U.S. residence were associated with better health for Latinas in the NHIS but not those in Birmingham. CONCLUSIONS: In this study of Latina immigrants in a new settlement community in the south, women reported worse health than foreign-born Latinas in other U.S. regions, suggesting they may be at increased risk of adverse health outcomes. Future studies are needed to better understand the factors associated with these differences to reduce morbidity and mortality burdens. PMID- 26263237 TI - Lipid Interventions in Aortic Valvular Disease. AB - Aortic valve stenosis is the most common valvular disease in the elderly population. Presently, there is increasing evidence that aortic stenosis (AS) is an active process of lipid deposition, inflammation, fibrosis and calcium deposition. The pathogenesis of AS shares many similarities to that of atherosclerosis; therefore, it was hypothesized that certain lipid interventions could prevent or slow the progression of aortic valve stenosis. Despite the early enthusiasm that statins may slow the progression of AS, recent large clinical trials did not consistently demonstrate a decrease in the progression of AS. However, some researchers believe that statins may have a benefit early on in the disease process, where inflammation (and not calcification) is the predominant process, in contrast to severe or advanced AS, where calcification (and not inflammation) predominates. Positron emission tomography using 18F fluorodeoxyglucose and 18F-sodium fluoride can demonstrate the relative contributions of valvular calcification and inflammation in AS, and thus this method might potentially be useful in providing the answer as to whether lipid interventions at the earlier stages of AS would be more effective in slowing the progression of the disease. Currently, there is a strong interest in recombinant apolipoprotein A-1 Milano and in the development of new pharmacological agents, targeting reduction of lipoprotein (a) levels and possibly reduction of the expression of lipoprotein-associated phospholipase A2, as potential means to slow the progression of aortic valvular stenosis. PMID- 26263238 TI - Separation and identification of bioactive compounds in Anabasis articulata (Forsk) Moq. roots. AB - In the present paper, for the first time, we are interested to separate and identify some bioactive fractions isolated from the roots of a Saharan plant Anabasis articulata, which is widely used in traditional medicine against cancer. The crude methanolic extract of the roots was fractionated on column chromatography, and eluted with dichloromethane/methanol each time with increasing polarity of methanol; 17 fractions were separated. One of these fractions named F12 showed more antioxidant activity to scavenge DPPH free radical with percentage inhibition of 95.29%. F12 was separated by thin-layer chromatography (TLC) to give 12 compounds. A second preparative TLC of compound 2, which has antioxidative activity of 74.92%, provided the three phenolic acids M1, M2 and M3, analysed by high-performance liquid chromatography and UV-visible spectrophotometry. PMID- 26263239 TI - Synthesis of alpha-Functionalized Trichloromethylcarbinols. AB - A new series of alpha-functionalized trichloromethylcarbinols have been synthesized from corresponding alpha-halomethyl ketones, esters, and amides in 48 78% overall yields. Reactivity of nitrates obtained in the first step was dependent on the electron-withdrawing nature of the functional groups, and increases with increasing electron deficiency. Synthetic applications of such trichloromethylcarbinols for the preparation of chloromethyl-alpha-diketones, trichloromethylated dihydrofurans, and enol acetates of alpha-functionalized acid chlorides have been demonstrated. The reaction of these compounds in the Jocic Reeve reaction was also demonstrated. PMID- 26263240 TI - RESPONSE OF UVEAL METASTASES TO ALK INHIBITORS IN ALK-POSITIVE NON-SMALL-CELL LUNG CANCER. AB - PURPOSE: To present a case of uveal metastases in a patient with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer and the response to systemic ALK inhibitors. METHODS: A retrospective case report. A 75-year-old nonsmoker who has ALK-positive left upper bronchus adenocarcinoma-developed uveal metastases during his course of treatment. RESULTS: Initially, the patient's disseminated malignancy showed a significant response to crizotinib. However, because the bone metastases started progressing again and he developed bilateral ocular metastases, he was switched to ceritinib. After initiation of ceritinib therapy, the uveal melanomas have shown a significant decrease in thickness and no new lesions have developed. CONCLUSION: ALK inhibitors are an effective first line treatment in patients with ALK-positive uveal metastases secondary to ALK positive non-small-cell lung cancer. Despite the fact that crizotinib, a first generation ALK inhibitor, is initially effective in dealing with non-small-cell lung cancer and its metastases, resistance to it seems to develop on a regular basis. A second-generation ALK inhibitor, such as ceritinib, is also effective in overcoming this resistance in treating those with ALK-positive uveal metastases. PMID- 26263241 TI - Chronotropic Incompetence and Dynamic Postexercise Autonomic Dysfunction Are Associated with the Presence and Severity of Erectile Dysfunction. AB - BACKGROUND: Exercise stress testing (EST) is crucial to determine cardiovascular (CV) risk in men with erectile dysfunction (ED). Low exercise workload, a slower rate of recovery following exercise, and an impaired capacity to increase heart rate (HR) during exercise testing (chronotropic incompetence) are independent predictors of adverse CV outcomes. Aim of this study was to investigate the association between ED and EST parameters. METHODS: A total of 180 ED patients and 50 men without ED underwent maximal EST. Exercise parameters including exercise capacity (metabolic equivalents, METS), peak exercise time, HR at six METS, peak exercise, HR recovery (HRR) at 1 and 2 minutes and chronotropic index (CI) were evaluated in all individuals. Endothelial function was evaluated with flow-mediated dilatation (FMD) of the brachial artery. RESULTS: ED patients had lower peak exercise time and thus lower calculated exercise capacity (P < 0.001) and reduced CI (P < 0.01) compared to men without ED. There was a significant association of ED severity with duration of exercise, peak workload, HRR 2 minutes after exercise, and CI (all P < 0.05). There also was a positive relation of HRR and CI with FMD (all P < 0.05). CONCLUSIONS: This study shows interrelationships between exercise capacity, HRR, CI, and ED. Abnormal HRR and CI are associated with systemic endothelial dysfunction. These findings imply pathophysiological links and may have important implications for the estimation of cardiovascular risk in ED patients. PMID- 26263243 TI - The Importance of Polymorphism in Metal-Organic Framework Studies. AB - Polymorphic phase transitions remain frequently undetected in routine metal organic framework (MOF) studies; however, their discovery is of major importance in interpreting structure-property relationships. We herein report a reversible enantiotropic single-crystal to single-crystal polymorphic phase transition of a new microporous MOF [Eu(BDC)(NO3)(DMF)2]n (H2BDC = 1,4-benzenedicarboxylic acid; DMF = dimethylformamide). While modification 1LT at 170 K crystallizes in the monoclinic space group P21/c with unit cell dimensions of a = 17.673(2) A, b = 20.023(2) A, c = 10.555(9) A, beta = 90.129(4) degrees , modification 1HT at 290 K crystallizes in higher symmetry space group C2/c with unit cell dimensions of a = 17.200(7) A, b = 10.737(4) A, c = 10.684(4) A, beta = 90.136(2) degrees . This temperature-induced phase transition is accompanied by a small change in the solvent-accessible voids from 46.8 in 1LT to 49.8% in 1HT, which triggers a significant change in the adsorption properties as compared to a reported isostructural compound. Detailed investigations on the phase transition were studied with variable-temperature single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction, and differential scanning calorimetry measurements. The herein-presented investigations emphasize the importance of polymorphic phase transitions in routine MOF studies originating from low-temperature SCXRD data and high-temperature physical property characterizations in avoiding the use of a wrong structure in interpreting structure-property relationships. PMID- 26263242 TI - Epidermal growth factor receptor signalling regulates granulocyte-macrophage colony-stimulating factor production by airway epithelial cells and established allergic airway disease. AB - BACKGROUND: Airway epithelial cells (AEC) are increasingly recognized as a major signalling centre in the pathogenesis of allergic asthma. A previous study demonstrated that epithelial growth factor receptor (EGFR) signalling in AEC regulated key features of allergic airway disease. However, it is unclear what mediators are regulated by EGFR signalling in AEC, although the production of the pro-inflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM CSF) is EGFR dependent in keratinocytes. OBJECTIVES: To determine whether EGFR signalling regulates GM-CSF production by human AEC downstream of the clinically relevant mediators house dust mite (HDM) and interleukin (IL)-17A and in a mouse model of established allergic asthma. METHODS: EGFR inhibitors were used to determine whether EGFR signalling regulates GM-CSF production by cultured human AEC in response to HDM and IL-17A. The roles of EGFR ligands, p38 mitogen activated protein kinase (MAPK) and tumour necrosis factor-alpha (TNF-alpha) converting enzyme (TACE) were also assessed. To determine whether EGFR regulates GM-CSF as well as key asthma characteristics in vivo, mice were chronically exposed to HDM to establish allergic airway disease and then treated with the EGFR inhibitor Erlotinib. RESULTS: EGFR inhibition reduced HDM and IL-17A induced GM-CSF production in a dose-dependent manner in cultured human AEC. GM-CSF production also required amphiregulin, p38 MAPK signalling and protease/TACE activity. In mice with established allergic airway disease, EGFR inhibition reduced levels of GM-CSF and TNF-alpha, as well as airway hyperreactivity, cellular inflammation, smooth muscle thickening and goblet cell metaplasia without changes in IgE and Th1, Th2 and Th17 cytokines. CONCLUSIONS AND CLINICAL RELEVANCE: Results link HDM, IL-17A, amphiregulin, EGFR and GM-CSF in a mechanistic pathway in AEC and demonstrate that EGFR regulates GM-CSF production and the severity of established disease in a clinically relevant asthma model. These results identify the EGFR->GM-CSF axis as a target for therapeutic development. PMID- 26263244 TI - Longer-term outcome in the prevention of psychotic disorders by the Vienna omega 3 study. AB - Long-chain omega-3 polyunsaturated fatty acids (PUFAs) are essential for neural development and function. As key components of brain tissue, omega-3 PUFAs play critical roles in brain development and function, and a lack of these fatty acids has been implicated in a number of mental health conditions over the lifespan, including schizophrenia. We have previously shown that a 12-week intervention with omega-3 PUFAs reduced the risk of progression to psychotic disorder in young people with subthreshold psychotic states for a 12-month period compared with placebo. We have now completed a longer-term follow-up of this randomized, double blind, placebo-controlled trial, at a median of 6.7 years. Here we show that brief intervention with omega-3 PUFAs reduced both the risk of progression to psychotic disorder and psychiatric morbidity in general in this study. The majority of the individuals from the omega-3 group did not show severe functional impairment and no longer experienced attenuated psychotic symptoms at follow-up. PMID- 26263245 TI - Design, characterization and in vitro evaluation of novel shell crosslinked poly(butylene adipate)-co-N-succinyl chitosan nanogels containing loteprednol etabonate: A new system for therapeutic effect enhancement via controlled drug delivery. AB - This study reports on the development of a novel mucoadhesive and biocompatible shell-crosslinked nanogel system based on poly(butylene adipate) (PBA) and N succinyl chitosan (S-Cs) by coupling reaction with a new formulation method. For this purpose, two different molecular weights of dendrimerized PBA with amine terminated functional groups were synthesized separately and characterized well by FT-IR, (1)HNMR and GPC. The PBA nanoparticles containing loteprednol etabonate (LPE) prepared by O/W emulsion technique were reacted immediately with modified carboxylated chitosan via carbodiimide chemistry. TEM photographs of the nanoparticles and crosslinked nanoparticles displayed a spherical morphology closely corresponding to the results obtained by DLS. On The other hand, biodegradability, biocompatibility and bioadhesiveness of the prepared nanoparticles were also studied. It is concluded that the core-shell structured nanogels can be used as novel ocular drug delivery systems with appropriate loading capacity for slightly water soluble LPE as an anti-inflammatory drug. PMID- 26263246 TI - Regioselectively controlled synthesis of 3(5) (trifluoromethyl)pyrazolylbenzenesulfonamides and their effects on a pathological pain model in mice. AB - This study reports a facile and controllable synthetic method for the preparation of both 1,3- and 1,5-isomers of 4-(3(5)-aryl-3(5)-(trifluoromethyl)-1H-pyrazol-1 yl)benzenesulfonamides, as well as a new series of 4-(3-aryl-5-hydroxy-5 (trifluoromethyl)-4,5-dihydropyrazol-1-yl)benzenesulfonamides, from the cyclocondensation reaction of 4-aryl-1,1,1-trifluoro-4-methoxybut-3-en-2-ones or 1-aryl-4,4,4-trifluoro-butane-1,3-diones or their enolic forms with 4 hydrazinylbenzenesulfonamide. All compounds of the new series of 3-substituted 1 (4-benzenesulfonamide)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydropyrazoles were tested for their effect on a pathological pain model in mice. The compounds 3a, 3b, 3c, 3e, and 3f presented anti-hyperalgesic action, while the compounds 3a, 3c, 3d, 3f, and 3g exhibited anti-edematogenic effects, without causing locomotive disorders in animals, thus making them comparable to Celecoxib in an arthritic pain model. PMID- 26263247 TI - Synthesis of arabinose glycosyl sulfamides as potential inhibitors of mycobacterial cell wall biosynthesis. AB - A series of arabinose glycosyl sulfamides with varying alkyl chain types and lengths were synthesised as mimics of decaprenolphosphoarabinose (DPA), and as potential inhibitors of mycobacterial cell wall biosynthesis. Unprecedented conversion of the desired furanose to the thermodynamically more stable pyranose form occurred during final de-protection. Biological testing against Mycobacterium smegmatis revealed low to moderate anti-mycobacterial activity with marked dependence on alkyl chain length, which in the case of mono-substituted sulfamides was maximal for a C-10 chain. PMID- 26263248 TI - Conformational and Optical Characteristics of Unidirectionally Twisted Binaphthyl Bipyridyl Cyclic Dyads. AB - An axially chiral binaphthyl-bipyridyl cyclic dyad in which the two units are connected by short -CH2O- linkers was synthesized. Experimental and theoretical analyses indicate that the (R)-binaphthyl unit in the dyad induces (R)-chirality in the bipyridyl unit, both in the solid state and in solution. It is shown that vibrational circular dichroism (VCD) is useful to determine the twisting pattern of 2,2'-bipyridyl compounds. The dyad shows crystallization-induced emission enhancement (CIEE). PMID- 26263249 TI - Understanding the Adsorption Mechanism of Xe and Kr in a Metal-Organic Framework from X-ray Structural Analysis and First-Principles Calculations. AB - Enhancement of adsorption capacity and separation of radioactive Xe/Kr at room temperature and above is a challenging problem. Here, we report a detailed structural refinement and analysis of the synchrotron X-ray powder diffraction data of Ni-DODBC metal organic framework with in situ Xe and Kr adsorption at room temperature and above. Our results reveal that Xe and Kr adsorb at the open metal sites, with adsorption geometries well reproduced by DFT calculations. The measured temperature-dependent adsorption capacity of Xe is substantially larger than that for Kr, indicating the selectivity of Xe over Kr and is consistent with the more negative adsorption energy (dominated by van der Waals dispersion interactions) predicted from DFT. Our results reveal critical structural and energetic information about host-guest interactions that dictate the selective adsorption mechanism of these two inert gases, providing guidance for the design and synthesis of new MOF materials for the separation of environmentally hazardous gases from nuclear reprocessing applications. PMID- 26263250 TI - Dominant Decomposition Pathways for Ethereal Solvents in Li-O2 Batteries. AB - The promise of high specific energies for Li-O2 batteries has driven research toward the development of new compatible materials for this emerging technology. Obtained energies, however, fall short of the theoretical values partly due to parasitic chemistries arising from organic solvent decomposition during battery cycling. Electrolyte solvent and salt decomposition have also been identified as limiting factors for rechargeability of the battery. Although lithium trifluorosulfonamide (LiTFSI) dissolved in 1,2-dimethoxyethane (DME) has been shown to be a promising solvent/electrolyte candidate for Li-O2 batteries, significant challenges remain, namely minimizing decomposition of both the solvent and electrolyte salt during battery cycling. Herein, we provide spectroscopic labeling studies to identify the source of H2 at high potentials during charge and propose a decomposition pathway for DME to lithium formate and acetate products at low potentials. NMR studies were preformed to show that DME decomposes to lithium formate and acetate in aqueous Li2O2, products which are also observed after D2O workups on cathodes after discharge. Finally, we use density functional theory (DFT) to elucidate a mechanistic pathway for DME decomposition that is based on known organic oxidation processes. PMID- 26263251 TI - Nanopore Current Oscillations: Nonlinear Dynamics on the Nanoscale. AB - In this Letter, we describe theoretical modeling of an experimentally realized nanoscale system that exhibits the general universal behavior of a nonlinear dynamical system. In particular, we consider the description of voltage-induced current fluctuations through a single nanopore from the perspective of nonlinear dynamics. We briefly review the experimental system and its behavior observed and then present a simple phenomenological nonlinear model that reproduces the qualitative behavior of the experimental data. The model consists of a two dimensional deterministic nonlinear bistable oscillator experiencing both dissipation and random noise. The multidimensionality of the model and the interplay between deterministic and stochastic forces are both required to obtain a qualitatively accurate description of the physical system. PMID- 26263252 TI - Filtering with Electric Field: The Case of E. coli Porins. AB - Although the role of general bacterial porins is well established as main pathway for polar antibiotics, the molecular details of their mode-of-action are still under debate. Using molecular dynamics simulations and water as a probe, we demonstrated the strong ordering of water molecules, differently tuned along the axis of diffusion in the transversal direction. Preserved features and important differences were characterized for different channels, allowing to put forward a general model for molecular filtering. The intrinsic electric field, responsible for water ordering, (i) filters those dipolar molecules that can compensate the entropy decrease by dipole alignment in the restricted region and (ii) might create an additional barrier by changing direction when escaping from the restricted region. We tested this model using two antibiotics, cefepime and cefotaxime, through metadynamics free energy calculations. A rational drug design should take this into account for screening molecules with improved permeation properties. PMID- 26263253 TI - Fluorescent Ferroelectrics of Hydrogen-Bonded Pyrene Derivatives. AB - Organic materials with diverse molecular designs show multifunctional properties such as coupled ferroelectric, optical, ferromagnetic, and transport properties. We report the design of an alkylamide-substituted pyrene derivative displaying fluorescent ferroelectric properties coupled with electron transport properties. In solution phase, this compound displayed concentration-dependent fluorescence, whereas in xerogels, a fluorescent green organogel (>0.1 mM) and entangled nanofibers were observed. A discotic hexagonal columnar liquid crystalline phase was observed above 295 K due to intermolecular hydrogen bonding and pi-stacking interactions. The direction of the hydrogen-bonded chains could be inverted by the application of an external electric field along the pi-stacked column, resulting in ferroelectric polarization-electric field (P-E) hysteresis. The local electric field arising from the ferroelectric macrodipole moment arrangement along the pi-stacking direction affected the electron transport properties on the pi-stack of pyrenes, thus confirming the current-switching phenomena according to P-E hysteresis. We report that multifunctional properties such as ferroelectricity, fluorescence, and electron transport switching were successfully achieved in hydrogen-bonded dynamic pi-molecular assemblies. PMID- 26263254 TI - Demystifying PIFE: The Photophysics Behind the Protein-Induced Fluorescence Enhancement Phenomenon in Cy3. AB - Protein-induced fluorescence enhancement (PIFE) is a term used to describe the increase in fluorescence intensity observed when a protein binds to a nucleic acid in the proximity of a fluorescent probe. PIFE using the single-molecule dye Cy3 is gaining popularity as an approach to investigate the dynamics of proteins that interact with nucleic acids. In this work, we used complexes of DNA and Klenow fragment and a combination of time-resolved fluorescence and transient spectroscopy techniques to elucidate the photophysical mechanism that leads to protein-enhanced fluorescence emission of Cy3 when in close proximity to a protein (PIFE). By monitoring the formation of the cis isomer directly, we proved that the enhancement of Cy3 fluorescence correlates with a decrease in the efficiency of photoisomerization, and occurs in conditions where the dye is sterically constrained by the protein. PMID- 26263255 TI - Mode-Specific Tunneling Splittings for a Sequential Double-Hydrogen Transfer Case: An Accurate Quantum Mechanical Scheme. AB - We present the first accurate quantum dynamics calculations of mode-specific tunneling splittings in a sequential double-hydrogen transfer process. This is achieved in the vinylidene-acetylene system, the simplest molecular system of this kind, and by large-scale parallel computations with an efficient theoretical scheme developed by us. In our scheme, basis functions are customized for the hydrogen transfer process; a 4-dimensional basis contraction strategy is combined with the preconditioned inexact spectral transform method; efficient parallel implementation is achieved. Mode-specific permutation tunneling splittings of vinylidene states are reported and tremendous mode-specific promotion effects are revealed; in particular, the CH2 rock mode enhances the ground-state splitting by a factor of 10(3). We find that the ground-state vinylidene has a reversible isomerization time of 622 ps, much longer than all previous estimates. Our calculations also shed light on the importance of the deep intermediate well and vibrational excitation in the double-hydrogen transfer processes. PMID- 26263256 TI - Synthetic Conditions for High-Accuracy Size Control of PbS Quantum Dots. AB - Decreasing the variability in quantum dot (QD) syntheses is desirable for better uniformity of samples for use in QD-based studies and applications. Here we report a highly reproducible linear relationship between the concentration of ligand (in this case oleic acid, OA) and the lowest energy exciton peak position (nm) of the resulting PbS QDs for various hot-injection temperatures. Thus, for a given injection temperature, the size of the PbS QD product is purely controlled by the amount of OA. We used this relationship to study PbS QD solar cells that are fabricated from the same size of PbS QDs but synthesized using four different injection temperatures: 95, 120, 150, and 185 degrees C. We find that the power conversion efficiency does not depend on injection temperature but that the V(oc) is higher for QDs synthesized at lower temperatures while the J(sc) is improved in higher temperature QDs. PMID- 26263257 TI - Macroscopic Molecular Ordering and Exciton Delocalization in Crystalline Phthalocyanine Thin Films. AB - We present spatially-, temporally- and polarization-resolved dual photoluminescence/linear dichroism microscopy experiments that investigate the correlation between long-range order and the nature of exciton states in solution processed phthalocyanine thin films. The influence of grain boundaries and disorder is absent in these films because typical grain sizes are 3 orders of magnitude larger than focused excitation beam diameters. These experiments reveal the existence of a delocalized singlet exciton, polarized along the high mobility axis in this quasi-1D electronic system. The strong delocalized pi orbitals overlap, controlled by the molecular stacking along the high mobility axis, is responsible for breaking the radiative recombination selection rules. Using our linear dichroism scanning microscopy setup, we further established that a rotation of molecules (i.e., a structural phase transition) that occurs above 100 K prevents the observation of this exciton at room temperature. PMID- 26263258 TI - How Morphology Affects Singlet Fission in Crystalline Tetracene. AB - The dependence of exciton dynamics on the crystalline morphology of tetracene is investigated using time-resolved photoluminescence. Single crystals exhibit relatively slow singlet decays with times that range from 130 to 300 ps depending on the sample. This decay has an activation energy of ~450 cm(-1) over the temperature range of 200-400 K. Single-crystal samples also exhibit more pronounced quantum beats due to the triplet pair spin coherences. Polycrystalline thin films grown by thermal evaporation have singlet decay times on the order of 70-90 ps with a much weaker temperature dependence. Many thin-film samples also exhibit a red-shifted excimer-like emission. When a polycrystalline thin film is thermally annealed to produce larger crystal domains, single-crystal behavior is recovered. We hypothesize that the different dynamics arise from the ability of singlet excitons in the thin films to sample regions with defects or packing motifs that accelerate singlet fission. PMID- 26263259 TI - Diffuse Surface Scattering in the Plasmonic Resonances of Ultralow Electron Density Nanospheres. AB - Localized surface plasmon resonances (LSPRs) have recently been identified in extremely diluted electron systems obtained by doping semiconductor quantum dots. Here, we investigate the role that different surface effects, namely, electronic spill-out and diffuse surface scattering, play in the optical properties of these ultralow electron density nanosystems. Diffuse scattering originates from imperfections or roughness at a microscopic scale on the surface. Using an electromagnetic theory that describes this mechanism in conjunction with a dielectric function including the quantum size effect, we find that the LSPRs show an oscillatory behavior in both position and width for large particles and a strong blue shift in energy and an increased width for smaller radii, consistent with recent experimental results for photodoped ZnO nanocrystals. We thus show that the commonly ignored process of diffuse surface scattering is a more important mechanism affecting the plasmonic properties of ultralow electron density nanoparticles than the spill-out effect. PMID- 26263260 TI - Mixed Quantum/Classical Approach for Description of Molecular Collisions in Astrophysical Environments. AB - An efficient and accurate mixed quantum/classical theory approach for computational treatment of inelastic scattering is extended to describe collision of an atom with a general asymmetric-top rotor polyatomic molecule. Quantum mechanics, employed to describe transitions between the internal states of the molecule, and classical mechanics, employed for description of scattering of the atom, are used in a self-consistent manner. Such calculations for rotational excitation of HCOOCH3 in collisions with He produce accurate results at scattering energies above 15 cm(-1), although resonances near threshold, below 5 cm(-1), cannot be reproduced. Importantly, the method remains computationally affordable at high scattering energies (here up to 1000 cm(-1)), which enables calculations for larger molecules and at higher collision energies than was possible previously with the standard full-quantum approach. Theoretical prediction of inelastic cross sections for a number of complex organic molecules observed in space becomes feasible using this new computational tool. PMID- 26263261 TI - Control of Nanostructures and Interfaces of Metal Oxide Semiconductors for Quantum-Dots-Sensitized Solar Cells. AB - Nanostructured metal oxide semiconductors (MOS), such as TiO2 and ZnO, have been regarded as an attractive material for the quantum dots sensitized solar cells (QDSCs), owing to their large specific surface area for loading a large amount of quantum dots (QDs) and strong scattering effect for capturing a sufficient fraction of photons. However, the large surface area of such nanostructures also provides easy pathways for charge recombination, and surface defects and connections between adjacent nanoparticles may retard effective charge injection and charge transport, leading to a loss of power conversion efficiency. Introduction of the surface modification for MOS or QDs has been thought an effective approach to improve the performance of QDSC. In this paper, the recent advances in the control of nanostructures and interfaces in QDSCs and prospects for the further development with higher power conversion efficiency (PCE) have been discussed. PMID- 26263262 TI - Synergistic Effects in the Coupling of Plasmon Resonance of Metal Nanoparticles with Excited Gold Clusters. AB - When molecules or clusters are within the proximity of metal particles, their electronic transitions can be drastically enhanced. We have now probed the off resonance excitation of molecule-like, glutathione-capped gold clusters (Au-GSH) in the close proximity of larger (plasmonic) Au and Ag nanoparticles. The excited state absorption spectrum of Au-GSH* is obtained with monophotonic excitation. The characteristic absorption of Au-GSH* allows us to probe the influence of excited plasmonic nanoparticles coupled with the clusters. Although infrared (775 nm) lasers pulses do not produce Au-GSH*, the excited states of these clusters are formed when coupled with metal (Au, Ag) nanoparticles. Interestingly, the coupled excitation of Au-GSH/AgNP with 775 nm laser pulses also results in an enhanced field effect, as seen from increased plasmon response of the metal nanoparticles. Transient absorption measurements confirm the synergy between these two inherently different nanomaterials, causing them to display greater excitation features. Better understanding of metal cluster-metal nanoparticle interactions will have important implications in designing light harvesting systems, and optoelectronic devices. PMID- 26263263 TI - Insights into How Fluorine-Adsorption and n-Type Doping Affect the Relative Stability of the (001) and (101) Surfaces of TiO2: Enhancing the Exposure of More Active but Thermodynamically Less Stable (001). AB - The stability of both the pure and fluorine (F)-adsorbed surface of TiO2 is examined on the basis of density functional calculations. For pure surfaces, both the beneficial local geometric structures and local potential strengthen the Ti-O binding in (101), rendering it the most stable surface. For F-adsorbed surfaces, F-adsorption significantly weakens the Ti-O bonds in (101) but strengthens them in (001), so that (001) becomes more stable than (101) for the F-adsorbed surfaces. On the basis of this observation, we further show that the n-type doping in TiO2 can significantly decrease the ability of F-adsorption in switching the relative stability of the two surfaces. The present work not only provides new insights into the physical and chemical properties about both pure and F-adsorbed surfaces of TiO2 and conclusively explains related experimental results but also suggests viable ways to prepare TiO2 samples with a high percentage of (001). PMID- 26263264 TI - Bright Visible-Infrared Light Emitting Diodes Based on Hybrid Halide Perovskite with Spiro-OMeTAD as a Hole-Injecting Layer. AB - Hybrid halide perovskites that are currently intensively studied for photovoltaic applications, also present outstanding properties for light emission. Here, we report on the preparation of bright solid state light emitting diodes (LEDs) based on a solution-processed hybrid lead halide perovskite (Pe). In particular, we have utilized the perovskite generally described with the formula CH3NH3PbI(3 x)Cl(x) and exploited a configuration without electron or hole blocking layer in addition to the injecting layers. Compact TiO2 and Spiro-OMeTAD were used as electron and hole injecting layers, respectively. We have demonstrated a bright combined visible-infrared radiance of 7.1 W.sr(-1).m(-2) at a current density of 232 mA.cm(-2), and a maximum external quantum efficiency (EQE) of 0.48%. The devices prepared surpass the EQE values achieved in previous reports, considering devices with just an injecting layer without any additional blocking layer. Significantly, the maximum EQE value of our devices is obtained at applied voltages as low as 2 V, with a turn-on voltage as low as the Pe band gap (V(turn on) = 1.45 +/- 0.06 V). This outstanding performance, despite the simplicity of the approach, highlights the enormous potentiality of Pe-LEDs. In addition, we present a stability study of unsealed Pe-LEDs, which demonstrates a dramatic influence of the measurement atmosphere on the performance of the devices. The decrease of the electroluminescence (EL) under continuous operation can be attributed to an increase of the non-radiative recombination pathways, rather than a degradation of the perovskite material itself. PMID- 26263265 TI - Anisotropy Effects on the Plasmonic Response of Nanoparticle Dimers. AB - We present an ab initio study of the anisotropy and atomic relaxation effects on the optical properties of nanoparticle dimers. Special emphasis is placed on the hybridization process of localized surface plasmons, plasmon-mediated photoinduced currents, and electric-field enhancement in the dimer junction. We show that there is a critical range of separations between the clusters (0.1-0.5 nm) in which the detailed atomic structure in the junction and the relative orientation of the nanoparticles have to be considered to obtain quantitative predictions for realistic nanoplasmonic devices. It is worth noting that this regime is characterized by the emergence of electron tunneling as a response to the driven electromagnetic field. The orientation of the particles not only modifies the attainable electric field enhancement but can lead to qualitative changes in the optical absorption spectrum of the system. PMID- 26263266 TI - Origin of Multiple Peaks in the Potentiodynamic Oxidation of CO Adlayers on Pt and Ru-Modified Pt Electrodes. AB - The study of the electrooxidation mechanism of CO(ad) on Pt based catalysts is very important for designing more effective CO-tolerant electrocatalysts for fuel cells. We have studied the origin of multiple peaks in the cyclic voltammograms of CO stripping from polycrystalline Pt and Ru modified polycrystalline Pt (Pt/Ru) surfaces in both acidic and alkaline media by differential electrochemical mass spectrometry (DEMS), DFT calculations, and kinetic Monte Carlo (KMC) simulations. A new CO(ad) electrooxidation kinetic model on heterogeneous Pt and Pt/Ru catalysts is proposed to account for the multiple peaks experimentally observed. In this model, OH species prefer to adsorb at low coordination sites or Ru sites and, thus, suppress CO repopulation from high coordination sites onto these sites. Therefore, CO(ad) oxidation occurs on different facets or regions, leading to multiplicity of CO stripping peaks. This work provides a new insight into the CO electrooxidation mechanism and kinetics on heterogeneous catalysts. PMID- 26263267 TI - Best Practice in Photocatalysis: Comparing Rates or Apparent Quantum Yields? PMID- 26263268 TI - Colloidal Organohalide Perovskite Nanoplatelets Exhibiting Quantum Confinement. AB - We prepare colloidal nanoplatelets of methylammonium lead bromide (MAPbBr3) perovskite and compare the optical signatures of excitons in these two dimensional systems to spherical perovskite nanocrystals and the corresponding bulk phase. We find that excitonic features that had previously been attributed to quantum confinement in MAPbBr3 nanocrystals are in fact a property of the bulk perovskite phase. Furthermore, we find that higher-energy absorption features originate from two-dimensional nanoplatelets, which are present in the nanocrystal reaction product. Upon further purification, we obtain colloidal nanoplatelets with predominantly single unit cell thickness and submicron lateral dimensions, which are stable in solution and exhibit a sharp excitonic absorption feature 0.5 eV blue-shifted from that of the three-dimensional bulk MAPbBr3 phase, representing a new addition to the growing family of colloidal two dimensional nanostructures. PMID- 26263269 TI - Solar Cells versus Solar Fuels: Two Different Outcomes. PMID- 26263270 TI - Understanding the Dual Nature of the Filament Dissolution in Conductive Bridging Devices. AB - The formation and rupture of conductive filaments (CFs) inside an insulating medium is used as hardware encoding of the state of a memory cell ("1" - "0") in filamentary-based conductive bridging memories. Currently accepted models explain the filament erase (reset) as the subtraction of conductive metal atoms from the CF; however, they do not fully account for the rich set of phenomena experimentally observed during the reset. The details of the filament erase are unraveled on the nanometer scale by means of an atomic force microscopy-based tomography technique enabling the 3D observation of erased CFs. "Non-broken" and "broken" CFs are observed, whereby the increase in resistance originates, respectively, from a constriction point in the current path and from an interrupted CF. We demonstrate that their existence and morphology can be related to the specific formation history of the CF, and we identify the physical volume of the CF as being mainly responsible for the type of filament erase. PMID- 26263271 TI - First-Principle Characterization for Singlet Fission Couplings. AB - The electronic coupling for singlet fission, an important parameter for determining the rate, has been found to be too small unless charge-transfer (CT) components were introduced in the diabatic states, mostly through perturbation or a model Hamiltonian. In the present work, the fragment spin difference (FSD) scheme was generalized to calculate the singlet fission coupling. The largest coupling strength obtained was 14.8 meV for two pentacenes in a crystal structure, or 33.7 meV for a transition-state structure, which yielded a singlet fission lifetime of 239 or 37 fs, generally consistent with experimental results (80 fs). Test results with other polyacene molecules are similar. We found that the charge on one fragment in the S1 diabatic state correlates well with FSD coupling, indicating the importance of the CT component. The FSD approach is a useful first-principle method for singlet fission coupling, without the need to include the CT component explicitly. PMID- 26263272 TI - Strain-Induced Segregation in Bimetallic Multiply Twinned Particles. AB - We analyze the possibility of strain-induced segregation in bimetallic multiply twinned particles by an analytic first-order expansion within a continuum model. The results indicate that while the change in free energy may be small, there will be a noticeable segregation of larger atoms to the external surface and smaller ones to the core, which could have interesting effects when such nanoparticles are used as heterogeneous catalysts. PMID- 26263273 TI - Disrupted Attosecond Charge Carrier Delocalization at a Hybrid Organic/Inorganic Semiconductor Interface. AB - Despite significant interest in hybrid organic/inorganic semiconductor interfaces, little is known regarding the fate of charge carriers at metal oxide interfaces, particularly on ultrafast time scales. Using core-hole clock spectroscopy, we investigate the ultrafast charge carrier dynamics of conductive ZnO films at a hybrid interface with an organic semiconductor. The adsorption of C60 on the ZnO surface strongly suppresses the ultrafast carrier delocalization and increases the charge carrier residence time from 400 attoseconds to nearly 30 fs. Here, we show that a new hybridized interfacial density of states with substantial molecular character is formed, fundamentally altering the observed carrier dynamics. The remarkable change in the dynamics sheds light on the fate of carriers at hybrid organic/inorganic semiconductor interfaces relevant to organic optoelectronics and provides for the first time an atomistic picture of the electronically perturbed near-interface region of a metal oxide. PMID- 26263274 TI - Photophysical Properties of a Post-Self-Assembly Host/Guest Coordination Cage: Visible Light Driven Core-to-Cage Charge Transfer. AB - Supramolecular systems are capable of unique photophysical properties due to possible interactions between subcomponents, such as between an encapsulated molecule and its cage in a host/guest environment. Here, we report that the encapsulation of a chromophore by a metallacage dramatically enhances its photophysical properties. In the visible region, the encapsulated photosensitizer achieves a 6.5-fold enhancement to its absorptivity. The triplet lifetime of the encapsulated photosensitizer is three times longer than that of its free analogue. These enhancements are attributed to two key factors: (i) encapsulation induced core-to-cage charge transfer (CCCT) generates new visible-light absorbing states, accounting for the enhanced absorption, and (ii) the microenvironment inside the metallacage inhibits nonradiative decay processes, resulting in prolonged triplet lifetime. The CCCT arises from the electrostatic interaction between the delocalized electrons of the guest coronene and the positive charge associated with the metallacage host. The work herein provides insight into the CCCT phenomenon. PMID- 26263275 TI - Intrinsic Material Properties Dictating Oxygen Vacancy Formation Energetics in Metal Oxides. AB - Oxygen vacancies (V(O)) in oxides are extensively used to manipulate vital material properties. Although methods to predict defect formation energies have advanced significantly, an understanding of the intrinsic material properties that govern defect energetics lags. We use first-principles calculations to study the connection between intrinsic (bulk) material properties and the energy to form a single, charge neutral oxygen vacancy (E(V)). We investigate 45 binary and ternary oxides and find that a simple model which combines (i) the oxide enthalpy of formation (DeltaH(f)), (ii) the midgap energy relative to the O 2p band center (E(O 2p) + (1/2)E(g)), and (iii) atomic electronegativities reproduces calculated E(V) within ~0.2 eV. This result provides both valuable insights into the key properties influencing E(V) and a direct method to predict E(V). We then predict the E(V) of ~1800 oxides and validate the predictive nature of our approach against direct defect calculations for a subset of 18 randomly selected materials. PMID- 26263276 TI - Effects of Different Quantum Coherence on the Pump-Probe Polarization Anisotropy of Photosynthetic Light-Harvesting Complexes: A Computational Study. AB - Observations of oscillatory features in the 2D spectra of several photosynthetic complexes have led to diverged opinions on their origins, including electronic coherence, vibrational coherence, and vibronic coherence. In this work, effects of these different types of quantum coherence on ultrafast pump-probe polarization anisotropy are investigated and distinguished. We first simulate the isotropic pump-probe signal and anisotropy decay of the Fenna-Matthews-Olson (FMO) complex using a model with only electronic coherence at low temperature and obtain the same coherence time as in the previous experiment. Then, three model dimer systems with different prespecified quantum coherence are simulated, and the results show that their different spectral characteristics can be used to determine the type of coherence during the spectral process. Finally, we simulate model systems with different electronic-vibrational couplings and reveal the condition in which long time vibronic coherence can be observed in systems like the FMO complex. PMID- 26263277 TI - Heterogeneous Photocatalysis and Photoelectrocatalysis: From Unselective Abatement of Noxious Species to Selective Production of High-Value Chemicals. AB - Heterogeneous photocatalysis and photoelectrocatalysis have been considered as oxidation technologies to abate unselectively noxious species. This article focuses instead on the utilization of these methods for selective syntheses of organic molecules. Some promising reactions have been reported in the presence of various TiO2 samples and the important role played by the amorphous phase has been discussed. The low solubility of most of the organic compounds in water limits the utilization of photocatalysis. Dimethyl carbonate has been proposed as an alternative green organic solvent. The recovery of the products by coupling photocatalysis with pervaporation membrane technology seems to be a solution for future industrial applications. As far as photoelectrocatalysis is concerned, a decrease in recombination of the photogenerated pairs occurs, enhancing the rate of the oxidation reactions and the quantum yield. Another benefit is to avoid reaction(s) between the intermediates and the substrate, as anodic and cathodic reactions take place in different places. PMID- 26263278 TI - Computational Quantum Chemistry for Multiple-Site Heisenberg Spin Couplings Made Simple: Still Only One Spin-Flip Required. AB - We provide a simple procedure for using inexpensive ab initio calculations to compute exchange coupling constants, J(AB), for multiradical molecules containing both an arbitrary number of radical sites and an arbitrary number of unpaired electrons. For a system comprised of 2M unpaired electrons, one needs only to compute states having the S(z) quantum number M - 1. Conveniently, these are precisely the states that are accessed by the family of single spin-flip methods. Building an effective Hamiltonian with these states allows one to extract all of the J(AB) constants in the molecule. Unlike approaches based on density functional theory, this procedure relies on neither spin-contaminated states nor nonunique spin-projection formulas. A key benefit is that it is possible to obtain completely spin-pure exchange coupling constants with inexpensive ab initio calculations. A couple of examples are provided to illustrate the approach, including a 4-nickel cubane complex and a 6-chromium horseshoe complex with 18 entangled electrons. PMID- 26263279 TI - Isomer-Specific Spectroscopy of Benzene-(H2O)n, n = 6,7: Benzene's Role in Reshaping Water's Three-Dimensional Networks. AB - The water hexamer and heptamer are the smallest sized water clusters that support three-dimensional hydrogen-bonded networks, with several competing structures that could be altered by interactions with a solute. Using infrared-ultraviolet double resonance spectroscopy, we record isomer-specific OH stretch infrared spectra of gas-phase benzene-(H2O)(6,7) clusters that demonstrate benzene's surprising role in reshaping (H2O)(6,7). The single observed isomer of benzene (H2O)6 incorporates an inverted book structure rather than the cage or prism. The main conformer of benzene-(H2O)7 is an inserted-cubic structure in which benzene replaces one water molecule in the S4-symmetry cube of the water octamer, inserting itself into the water cluster by engaging as a pi H-bond acceptor with one water and via C-H...O donor interactions with two others. The corresponding D(2d)-symmetry inserted-cube structure is not observed, consistent with the calculated energetic preference for the S4 over the D(2d) inserted cube. A reduced-dimension model that incorporates stretch-bend Fermi resonance accounts for the spectra in detail and sheds light on the hydrogen-bonding networks themselves and on the perturbations imposed on them by benzene. PMID- 26263280 TI - Osteoporosis After Long-Term Depot Medroxyprogesterone: We Need More Data on Fracture Risk. PMID- 26263281 TI - Effects of Cardiovascular Disease on Compliance with Cervical and Breast Cancer Screening Recommendations Among Adult Women. AB - BACKGROUND: Cardiovascular disease (CVD) is common among women and is a leading cause of death in the United States. This study assessed the impact of CVD on compliance with the US Preventive Services Task Force guidelines for cervical and breast cancer screening among U.S. adult women. METHODS: A cross-sectional study was conducted on 17,408 women using data from the National Health Interview Survey 2013. A total of 11,788 respondents (21-65 years old) with complete information on Pap smear and 11,409 women (40+ years old) with complete information on mammography compliance were included. Multivariate logistic regression models were used to assess the impact of CVD on cervical and breast cancer screening practices. RESULTS: Women with CVD were marginally more likely to have had a mammogram in accordance with guidelines (odds ratio 1.17; 95% confidence interval 1.04-1.31) than those without CVD. However, compliance with Pap tests was similar (80.6% vs 82.3%, p>0.05) between the two groups. Myocardial infarction was associated with reduced odds of Pap smear compliance (odds ratio: 0.30; 95% confidence interval 0.18-0.51). CONCLUSIONS: Women with prior myocardial infarction should be encouraged to continue receiving regular Pap smears. More research is needed to assess whether observed differences in Pap testing between patients with and without a history of myocardial infarction result from lack of provider recommendation or from patient noncompliance with their recommendations. PMID- 26263282 TI - Vaginal estrogen use and effects on quality of life and urogenital morbidity in postmenopausal women after publication of the Women's Health Initiative in New York City. AB - OBJECTIVE: In the years after the 2002 publication of results from the Women's Health Initiative study, there has been a reluctance to prescribe hormone therapy to symptomatic postmenopausal women and confusion over its duration and method of prescription. The main concerns are the risks of cardiovascular events and breast cancer. However, local vaginal estrogen (VE) may provide benefits without systemic effects. METHODS: This study investigates the use and effects of VE on quality of life and urogenital morbidity among women who stopped hormone therapy after the Women's Health Initiative and compares them with women who continued hormone therapy. Three groups were compared: group 1, women who have remained on HT/ET; group 2, women who have resumed HT/ET after stopping for at least 6 months, and group 3, women who have stopped HT/ET and have not resumed. RESULTS: Overall, ever use and present use of VE were most prevalent in women who reported dyspareunia (ever, P = 0.003; present, P = 0.005) and vaginal dryness (ever, P = 0.001; present, P = 0.004). VE use was significantly more probable for women in group 3 than for women in the other groups (group 3 [3.5%] vs. group 1 [17.7%] and group 2 [16.7%]; P = 0.002). Women in group 3 who used VE reported significantly higher sexual quality of life (using the sexual domain of the Utian Quality of Life Scale) compared with women in group 3 who did not use VE (P = 0.007). There was no difference in the incidence of urinary tract infections between the three groups (group 1, 22.9%; group 2, 26.3%; group 3, 25.5%). The percentage of women who were either married or living in a marriage-like relationship did not differ between the three groups (group 1, 68.4%; group 2, 78.6%; group 3, 78.8%). CONCLUSIONS: Women who report dyspareunia and vaginal dryness are more likely to use VE. Women who do not use systemic therapy but use VE score significantly higher on the sexual quality-of-life scale than women not using VE. PMID- 26263284 TI - Differential effect of depression versus thermoregulation in postmenopausal sleep disturbance. PMID- 26263283 TI - Continuous transdermal nitroglycerin therapy for menopausal hot flashes: a single arm, dose-escalation trial. AB - OBJECTIVE: To describe the efficacy and tolerability of continuous nitroglycerin for treatment of hot flashes. METHODS: Perimenopausal and postmenopausal women reporting at least seven hot flashes per day were recruited into a single-arm, dose-escalation trial of continuous transdermal nitroglycerin. Participants were started on a generic 0.1 mg/hour nitroglycerin patch applied daily without patch free periods. During 4 weeks, participants escalated dosage weekly to 0.2, 0.4, or 0.6 mg/hour as tolerated, then discontinued nitroglycerin during the final week. Changes in hot flash frequency and severity were assessed using symptom diaries. Paired t tests examined change in outcomes between baseline and maximal dose therapy and after discontinuation of nitroglycerin. RESULTS: Of the 19 participants, mean age was 51.4 (+/-4.3) years. Women reported an average 10.6 (+/-3.0) hot flashes and 7.1 (+/-3.8) moderate-to-severe hot flashes per day at baseline. Eleven women escalated to 0.6 mg/hour, three to 0.4 mg/hour, two to 0.2 mg/hour, and one remained on 0.1 mg/hour nitroglycerin. Two discontinued nitroglycerin before the first outcomes assessment. Among the remaining 17 women, the average daily frequency of hot flashes decreased by 54% and the average frequency of moderate-to-severe hot flashes decreased by 69% from baseline to maximum-dose therapy (P < 0.001 for both). After discontinuing nitroglycerin, participants reported an average 23% increase in frequency of any hot flashes (P = 0.041) and 96% increase in moderate-to-severe hot flashes (P < 0.001). CONCLUSIONS: Continuous nitroglycerin may substantially and reversibly decrease hot flash frequency and severity. If confirmed in a randomized blinded trial, it may offer a novel nonhormonal hot flash treatment. PMID- 26263285 TI - Nurse Determination and Evolving Models of Care. PMID- 26263286 TI - Let's Go Fly a Kite. PMID- 26263287 TI - The Use of ShotBlocker for Reducing the Pain and Anxiety Associated With Intramuscular Injection: A Randomized, Placebo Controlled Study. AB - There are few studies evaluating the effect of ShotBlocker on pain acquired from intramuscular injection, and these are mostly in children. We hypothesized that the use of ShotBlocker, while administering an intramuscular injection, would reduce the pain and anxiety due to intramuscular injection in adults. A randomized, placebo controlled trial was carried out for more than 20 months in 2010-2011 on 180 adults aged 18 to 80 years who received intramuscular injections of diclofenac sodium (75 mg/3 mL) at the outpatient clinic of a hospital. The patients were grouped into 3 groups: control, placebo control, and experimental. The experimental group was given an intramuscular injection of diclofenac sodium with ShotBlocker. Pain intensity was measured through a visual analog scale after the injection and anxiety was measured using Spielberger's State-Trait Anxiety Inventory. Pulse rate was counted and state and trait anxiety was measured before and after the injection. The Mann-Whitney U test and Wilcoxon and Kruskall-Wallis tests were used to evaluate the data. Patients in the ShotBlocker group had significantly lower pain intensity than those in the placebo and control groups. State anxiety level increased after the injection in the experimental group but did not change in the other 2 groups. ShotBlocker did not affect the pulse rate. Our results suggest that using ShotBlocker during intramuscular injection reduced patients' pain intensity because of injection but did not reduce anxiety levels. Thus, ShotBlocker is recommended as a pain-relieving tool during intramuscular injection in adults. PMID- 26263288 TI - The Challenge of Diabetes in the Elderly and Affecting Factors: A Turkish Study. AB - This study was conducted with the goal of evaluating the challenge of diabetes in elderly individuals and affecting factors. This descriptive study was conducted with 88 diabetic patients 65 years of age or older who were admitted to the endocrinology and metabolism disorders outpatient clinic data of the study collected by using a questionnaire prepared by the researchers and the Elderly Diabetes Burden Scale. Total score of the scale varies between 19 and 92 points. While a higher score indicates a higher burden a lower score indicates a lower burden, data were analyzed by using Student t test, 1-way analysis of variance, Mann-Whitney U test, and Kruskal-Wallis test. Subscale and total mean scores of patients were as follows: 9.4 +/- 3.2 for symptom burden; 12.4 +/- 3.4 for social burden; 11.4 +/- 3.3 for burden by dietary restrictions; 11.9 +/- 3.7 for burden of worry about diabetes; 4.3 +/- 1.3 for burden from treatment dissatisfaction; 9.4 +/- 4.6 for burden by oral antidiabetic drugs or insulin; and 58.5 +/- 9.6 for total diabetes burden score. Diabetes burden was found to be higher for patients who were at an advanced age, single, female, had a lower income, receiving oral antidiabetic or insulin treatment, and had diabetes duration of 6 to 11 years, a concomitant chronic condition or a diabetic person among first degree relatives and who did not come for regular follow-up visits, had no assistance for their care, and who stated a poor quality of life and treatment compliance. Elderly diabetic patients were found to have a high total Elderly Diabetes Burden Scale score, and the highest scores were observed for the subscales of burden by dietary restrictions, social burden, and burden of worry about diabetes. Thus, it could be recommended to perform appropriate nursing interventions in order to assess and reduce diabetes challenge during planning of necessary treatment and care in elderly diabetic patients. PMID- 26263290 TI - Nursing Support of the Spiritual Needs of Older Adults Living With Dementia: A Narrative Literature Review. AB - Across this literature review (n = 10), supporting spirituality in the nursing care of older adults with dementia is concerned with supporting religious activity, enabling connections, nurses' reflections on their own spirituality, and nonverbal communication. The benefits from the support of spirituality were seen to be reciprocal and to occur in everyday nursing. PMID- 26263289 TI - A Narrative Literature Review of the Experiences of Patients Living With Heart Failure. AB - This article reviews the literature on the experiences of patients with heart failure and their coping strategies and learning needs. Previous studies have consistently demonstrated that heart failure had negative impacts on the individuals who experienced it. Studies have also focused on the learning needs and the various coping strategies that patients with heart failure have adopted. However, there are limited studies that have investigated the experience of heart failure from the Asian patient's perspective. By incorporating the perspectives of patients with heart failure from the Asian context into clinical practices, research will promote patient-centered holistic care and improve patients' quality of life and satisfaction. PMID- 26263291 TI - Preventing Loss of Basic Activities of Daily Living and Instrumental Activities of Daily Living in Elderly: Identification of Individual Risk Factors in a Holistic Perspective. AB - This study investigated the association between physical functioning and activities of daily living (ADL) of elderly people, taking into account the role of cognitive, psychological, and social factors. We administered physical, cognitive, psychological, and social instruments to investigate the level of basic and instrumental activities of daily living (BADL and IADL). The analysis showed that physical functioning was the only individual factor that was significantly linked with the level of BADL and IADL. This study underlines that physical functioning is the main individual characteristic directly associated with the level of BADL and IADL in old age. PMID- 26263292 TI - Harm/Loss, Threat, and Challenge of Living With Diabetes for Persons From Rural Appalachia: A Qualitative Study. AB - Living with the stress of diabetes involves suffering with pain, being frightened of the unknown, worrying about threats to family, trying to manage restrictions, taking on activities of living the everyday, and moving forward with confidence. The appraisal of the stress of diabetes indicates a need for development of person-centered interventions. PMID- 26263293 TI - Ginkgo biloba (EGb 761): A Proprietary Leaf Extract of Ginkgo biloba Is Found to be Safe and Effective for Treating Dementia. PMID- 26263294 TI - ANA's "Year of Ethics": Holistic Support for Safe, Quality Care. PMID- 26263296 TI - What can acute medicine learn from qualitative methods? AB - PURPOSE OF REVIEW: The contribution of qualitative methods to evidence-based medicine is growing, with qualitative studies increasingly used to examine patient experience and unsafe organizational cultures. The present review considers qualitative research recently conducted on teamwork and organizational culture in the ICU and also other acute domains. RECENT FINDINGS: Qualitative studies have highlighted the importance of interpersonal and social aspects of healthcare on managing and responding to patient care needs. Clear/consistent communication, compassion, and trust underpin successful patient-physician interactions, with improved patient experiences linked to patient safety and clinical effectiveness across a wide range of measures and outcomes. Across multidisciplinary teams, good communication facilitates shared understanding, decision-making and coordinated action, reducing patient risk in the process. SUMMARY: Qualitative methods highlight the complex nature of risk management in hospital wards, which is highly contextualized to the demands and resources available, and influenced by multilayered social contexts. In addition to augmenting quantitative research, qualitative investigations enable the investigation of questions on social behaviour that are beyond the scope of quantitative assessment alone. To develop improved patient-centred care, health professionals should therefore consider integrating qualitative procedures into their existing assessments of patient/staff satisfaction. PMID- 26263297 TI - Arterial blood pressure and heart rate regulation in shock state. AB - PURPOSE OF REVIEW: Circulatory shock is a complicated problem that carries a high risk of complications and mortality for critically ill patients. The heart rate and blood pressure targets to which a patient in shock should be resuscitated remain a challenge to intensivists. RECENT FINDINGS: While the ideal blood pressure and heart rate in circulatory shock are still not definitive, recent studies have begun to refine these targets. A recent trial comparing a mean arterial pressure target of 80-85 mmHg with a target of 65-70 mmHg showed no difference in mortality, with a decreased need for renal replacement therapy in patients with pre-existing hypertension based on subgroup analysis. Regulation of heart rate was defined by a trial demonstrating that heart rate control in patients with severe sepsis on high-dose norepinephrine with esmolol titration did not result in additional adverse events. SUMMARY: The ideal target blood pressure in the resuscitation of circulatory shock is variable and likely depends on prior blood pressure. Heart rate regulation with beta-blockade appears to be safe in selected patients when accompanied by adequate resuscitation and monitoring. PMID- 26263298 TI - New antibiotics and antimicrobial combination therapy for the treatment of gram negative bacterial infections. AB - PURPOSE OF REVIEW: Increasing rates of life-threatening infections due to multidrug-resistant (MDR) gram-negative bacteria, such as carbapenemase-producer strains, as well as pathogens that are resistant to all current therapeutic options, have been reported. The number of compounds that are currently being developed is still insufficient to control this global threat. We have reviewed the current available options for the treatment of MDR gram-negative infections, including combination regimens employing older antimicrobials and new compounds. RECENT FINDINGS: A limited number of large trials have assessed the treatment options for commonly encountered resistant pathogens (e.g., Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa). Antimicrobials that were used in the past, such as colistin and fosfomycin, have been recently resumed and used in association with carbapenems, tigecycline, or aminoglycosides, showing a positive impact on clinical outcomes. New compounds belonging to various antimicrobial classes (e.g. beta-lactamase inhibitors, cephalosporins, glycyclines, aminoglycosides) have been investigated. SUMMARY: Only few new molecules have an adequate activity against MDR gram-negative pathogens, especially carbapenemase-producer strains. Among these, ceftozolane/tazobactam has been recently approved for clinical use. Other compounds, such as avibactam combinations, plazomicin, and eravacycline, have shown promising activity in phase 2 and 3 clinical trials. PMID- 26263299 TI - Progress on core outcome sets for critical care research. AB - PURPOSE OF REVIEW: Appropriate selection and definition of outcome measures are essential for clinical trials to be maximally informative. Core outcome sets (an agreed, standardized collection of outcomes measured and reported in all trials for a specific clinical area) were developed due to established inconsistencies in trial outcome selection. This review discusses the rationale for, and methods of, core outcome set development, as well as current initiatives in critical care. RECENT FINDINGS: Recent systematic reviews of reported outcomes and measurement instruments relevant to the critically ill highlight inconsistencies in outcome selection, definition, and measurement, thus establishing the need for core outcome sets. Current critical care initiatives include development of core outcome sets for trials aimed at reducing mechanical ventilation duration; rehabilitation following critical illness; long-term outcomes in acute respiratory failure; and epidemic and pandemic studies of severe acute respiratory infection. SUMMARY: Development and utilization of core outcome sets for studies relevant to the critically ill is in its infancy compared to other specialties. Notwithstanding, core outcome set development frameworks and guidelines are available, several sets are in various stages of development, and there is strong support from international investigator-led collaborations including the International Forum for Acute Care Trialists. PMID- 26263300 TI - Enantioselective Liquid-Solid Extraction (ELSE)--An Unexplored, Fast, and Precise Analytical Method. AB - A novel method of evaluating the enantioselectivity of chiral receptors is investigated. It involves extraction of an ionic guest in racemic form from an ion-exchange resin to the organic solvent, where it is bound by a chiral receptor. The enantioselectivity of the examined receptor is determined simply by measuring the enantiomeric excess of the extracted guest. We show that the concept is viable for neutral receptors binding chiral organic anions extracted into acetonitile. This method was determined to be more accurate and far less time-consuming than the classical titrations. Multiple racemic guests can be applied to a resin in a single experiment, giving the method a very high throughput. PMID- 26263301 TI - Porous Au-Ag Alloy Particles Inlaid AgCl Membranes As Versatile Plasmonic Catalytic Interfaces with Simultaneous, in Situ SERS Monitoring. AB - We present a novel porous Au-Ag alloy particles inlaid AgCl membrane as plasmonic catalytic interfaces with real-time, in situ surface-enhanced Raman spectroscopy (SERS) monitoring. The Au-Ag alloy particles inlaid AgCl membranes were obtained via a facile two-step, air-exposed, and room-temperature immersion reaction with appropriate annealing process. Owing to the designed integration of semiconductor component AgCl and noble metal Au-Ag particles, both the catalytic reduction and visible-light-driven photocatalytic activities toward organic contaminants were attained. Specifically, the efficiencies of about 94% of 4-nitrophenol (4-NP, 5 * 10(-5) M) reduction after 8 min of reaction, and degradation of rhodamine 6G (R6G, 10(-5) M) after 12 min of visible light irradiation were demonstrated. Moreover, efficiencies of above 85% of conversion of 4-NP to 4-aminophenol (4-AP) and 90% of R6G degradation were achieved as well after 6 cycles of reactions, by which robust recyclability was confirmed. Further, with distinct SERS signals generated simultaneously from the surfaces of Au-Ag particles under laser excitation, in situ SERS monitoring of the process of catalytic reactions with superior sensitivity and linearity has been realized. Overall, the capability of the Au-Ag particles inlaid AgCl membranes to provide SERS monitored catalytic and visible-light-driven photocatalytic conversion of organic pollutants, along with their mild and cost-effective fabrication method, would make sense for in-depth understanding of the mechanisms of (photo)catalytic reactions, and also future development of potable, multifunctional and integrated catalytic and sensing devices. PMID- 26263303 TI - Capping Motif for Peptide Helix Formation. AB - It is known that a C-terminal lysine stabilizes helix formation in polyalanine peptides that have seven or more residues. Using a combination of cold ion spectroscopy and DFT calculations, we demonstrate that even a three-residue peptide, Ac-Phe-Ala-LysH(+), adopts a structure in which the lysine side chain forms three hydrogen bonds with backbone carbonyls, reproducing the capping motif of larger polyalanine helices. This is confirmed by comparison with Ac-Phe-(Ala)5 LysH(+), which forms a 310 helix containing the same structural feature. In both molecules, we identified the vibrational bands of the N- and C-terminal amide NH stretches, which lack strong hydrogen bonds with carbonyls and consequently appear in a characteristic region above 3400 cm(-1). A similar pattern is also present in the even longer peptide Ac-Phe-(Ala)10-LysH(+), illustrating the generality of this capping motif. The two longer peptides contain additional, characteristic amide NH stretch bands below 3400 cm(-1), which form the core of the helix. PMID- 26263302 TI - A Maximum-Likelihood Approach to Force-Field Calibration. AB - A new approach to the calibration of the force fields is proposed, in which the force-field parameters are obtained by maximum-likelihood fitting of the calculated conformational ensembles to the experimental ensembles of training system(s). The maximum-likelihood function is composed of logarithms of the Boltzmann probabilities of the experimental conformations, calculated with the current energy function. Because the theoretical distribution is given in the form of the simulated conformations only, the contributions from all of the simulated conformations, with Gaussian weights in the distances from a given experimental conformation, are added to give the contribution to the target function from this conformation. In contrast to earlier methods for force-field calibration, the approach does not suffer from the arbitrariness of dividing the decoy set into native-like and non-native structures; however, if such a division is made instead of using Gaussian weights, application of the maximum-likelihood method results in the well-known energy-gap maximization. The computational procedure consists of cycles of decoy generation and maximum-likelihood-function optimization, which are iterated until convergence is reached. The method was tested with Gaussian distributions and then applied to the physics-based coarse grained UNRES force field for proteins. The NMR structures of the tryptophan cage, a small alpha-helical protein, determined at three temperatures (T = 280, 305, and 313 K) by Halabis et al. ( J. Phys. Chem. B 2012 , 116 , 6898 - 6907 ), were used. Multiplexed replica-exchange molecular dynamics was used to generate the decoys. The iterative procedure exhibited steady convergence. Three variants of optimization were tried: optimization of the energy-term weights alone and use of the experimental ensemble of the folded protein only at T = 280 K (run 1); optimization of the energy-term weights and use of experimental ensembles at all three temperatures (run 2); and optimization of the energy-term weights and the coefficients of the torsional and multibody energy terms and use of experimental ensembles at all three temperatures (run 3). The force fields were subsequently tested with a set of 14 alpha-helical and two alpha + beta proteins. Optimization run 1 resulted in better agreement with the experimental ensemble at T = 280 K compared with optimization run 2 and in comparable performance on the test set but poorer agreement of the calculated folding temperature with the experimental folding temperature. Optimization run 3 resulted in the best fit of the calculated ensembles to the experimental ones for the tryptophan cage but in much poorer performance on the training set, suggesting that use of a small alpha helical protein for extensive force-field calibration resulted in overfitting of the data for this protein at the expense of transferability. The optimized force field resulting from run 2 was found to fold 13 of the 14 tested alpha-helical proteins and one small alpha + beta protein with the correct topologies; the average structures of 10 of them were predicted with accuracies of about 5 A C(alpha) root-mean-square deviation or better. Test simulations with an additional set of 12 alpha-helical proteins demonstrated that this force field performed better on alpha-helical proteins than the previous parametrizations of UNRES. The proposed approach is applicable to any problem of maximum-likelihood parameter estimation when the contributions to the maximum-likelihood function cannot be evaluated at the experimental points and the dimension of the configurational space is too high to construct histograms of the experimental distributions. PMID- 26263304 TI - Anisotropic Ripple Deformation in Phosphorene. AB - Two-dimensional materials tend to become crumpled according to the Mermin-Wagner theorem, and the resulting ripple deformation may significantly influence electronic properties as observed in graphene and MoS2. Here, we unveil by first principles calculations a new, highly anisotropic ripple pattern in phosphorene, a monolayer black phosphorus, where compression-induced ripple deformation occurs only along the zigzag direction in the strain range up to 10%, but not the armchair direction. This direction-selective ripple deformation mode in phosphorene stems from its puckered structure with coupled hinge-like bonding configurations and the resulting anisotropic Poisson ratio. We also construct an analytical model using classical elasticity theory for ripple deformation in phosphorene under arbitrary strain. The present results offer new insights into the mechanisms governing the structural and electronic properties of phosphorene crucial to its device applications. PMID- 26263305 TI - Regulating Ion Transport in Peptide Nanotubes by Tailoring the Nanotube Lumen Chemistry. AB - We use atomistic nonequilibrium molecular dynamics simulations to demonstrate how specific ionic flux in peptide nanotubes can be regulated by tailoring the lumen chemistry through single amino acid substitutions. By varying the size and polarity of the functional group inserted into the nanotube interior, we are able to adjust the Na(+) flux by over an order of magnitude. Cl(-) is consistently denied passage. Bulky, nonpolar groups encourage interactions between the Na(+) and the peptide backbone carbonyl groups, disrupting the Na(+) solvation shell and slowing the transport of Na(+). Small groups have the opposite effect and accelerate flow. These results suggest that relative ion flux and selectivity can be precisely regulated in subnanometer pores by molecularly defining the lumen according to biological principles. PMID- 26263306 TI - Negative Differential Resistance Probe for Interdot Interactions in a Double Quantum Dot Array. AB - Colloidal quantum dots are free-standing nanostructures with chemically tunable electronic properties. In this work, we consider a new STM tip-double quantum dot (DQD)-surface setup with a unique connectivity, in which the tip is coupled to a single dot and the coupling to the surface is shared by both dots. Our theoretical analysis reveals a unique negative differential resistance (NDR) effect attributed to destructive interference during charge transfer from the DQD to the surface. This NDR can be used as a sensitive probe for interdot interactions in DQD arrays. PMID- 26263307 TI - Conditional Born-Oppenheimer Dynamics: Quantum Dynamics Simulations for the Model Porphine. AB - We report a new theoretical approach to solve adiabatic quantum molecular dynamics halfway between wave function and trajectory-based methods. The evolution of a N-body nuclear wave function moving on a 3N-dimensional Born Oppenheimer potential-energy hyper-surface is rewritten in terms of single-nuclei wave functions evolving nonunitarily on a 3-dimensional potential-energy surface that depends parametrically on the configuration of an ensemble of generally defined trajectories. The scheme is exact and, together with the use of trajectory-based statistical techniques, can be exploited to circumvent the calculation and storage of many-body quantities (e.g., wave function and potential-energy surface) whose size scales exponentially with the number of nuclear degrees of freedom. As a proof of concept, we present numerical simulations of a 2-dimensional model porphine where switching from concerted to sequential double proton transfer (and back) is induced quantum mechanically. PMID- 26263308 TI - Molecular Growth Inside of Polycyclic Aromatic Hydrocarbon Clusters Induced by Ion Collisions. AB - The present work combines experimental and theoretical studies of the collision between keV ion projectiles and clusters of pyrene, one of the simplest polycyclic aromatic hydrocarbons (PAHs). Intracluster growth processes induced by ion collisions lead to the formation of a wide range of new molecules with masses larger than that of the pyrene molecule. The efficiency of these processes is found to strongly depend on the mass and velocity of the incoming projectile. Classical molecular dynamics simulations of the entire collision process-from the ion impact (nuclear scattering) to the formation of new molecular species reproduce the essential features of the measured molecular growth process and also yield estimates of the related absolute cross sections. More elaborate density functional tight binding calculations yield the same growth products as the classical simulations. The present results could be relevant to understand the physical chemistry of the PAH-rich upper atmosphere of Saturn's moon Titan. PMID- 26263309 TI - Rain on Methylammonium Lead Iodide Based Perovskites: Possible Environmental Effects of Perovskite Solar Cells. AB - The great promise of hybrid organic-inorganic lead halide perovskite (HOIP)-based solar cells is being challenged by its Pb content and its sensitivity to water. Here, the impact of rain on methylammonium lead iodide perovskite films was investigated by exposing such films to water of varying pH values, simulating exposure of the films to rain. The amount of Pb loss was determined using both gravimetric and inductively coupled plasma mass spectrometry measurements. Using our results, the extent of Pb loss to the environment, in the case of catastrophic module failure, was evaluated. Although very dependent on module siting, even total destruction of a large solar electrical power generating plant, based on HOIPs, while obviously highly undesirable, is estimated to be far from catastrophic for the environment. PMID- 26263310 TI - Correction to "Orientation-Dependent Oxygen Evolution Activities of Rutile IrO2 and RuO2". PMID- 26263311 TI - Atomic Clusters: Opportunities in the Face of Challenges. PMID- 26263312 TI - Stereodynamical Origin of Anti-Arrhenius Kinetics: Negative Activation Energy and Roaming for a Four-Atom Reaction. AB - The OH + HBr -> H2O + Br reaction, prototypical of halogen-atom liberating processes relevant to mechanisms for atmospheric ozone destruction, attracted frequent attention of experimental chemical kinetics: the nature of the unusual reactivity drop from low to high temperatures eluded a variety of theoretical efforts, ranking this one among the most studied four-atom reactions. Here, inspired by oriented molecular-beams experiments, we develop a first-principles stereodynamical approach. Thermalized sets of trajectories, evolving on a multidimensional potential energy surface quantum mechanically generated on-the fly, provide a map of most visited regions at each temperature. Visualizations of rearrangements of bonds along trajectories and of the role of specific angles of reactants' mutual approach elucidate the mechanistic change from the low kinetic energy regime (where incident reactants reorient to find the propitious alignment leading to reaction) to high temperature (where speed hinders adjustment of directionality and roaming delays reactivity). PMID- 26263313 TI - Lattice Strain Limit for Uniform Shell Deposition in Zincblende CdSe/CdS Quantum Dots. AB - The effects of lattice strain on the spectroscopy and photoluminescence quantum yields of zincblende CdSe/CdS core/shell quantum dots are examined. The quantum yields are measured as a function of core size and shell thickness. High quantum yields are achieved as long as the lattice strain energy density is below ~0.85 eV/nm(2), which is considerably greater than the limiting value of 0.59 eV/nm(2) for thermodynamic stability of a smooth, defect-free shell, as previously reported (J. Chem. Phys. 2014, 141, 194704). Thus, core/shell quantum dots having strain energy densities between 0.59 and 0.85 eV/nm(2) can have very high PL QYs but are metastable with respect to surface defect formation. Such metastable core/shell QDs can be produced by shell deposition at comparatively low temperatures (<140 degrees C). Annealing of these particles causes partial loss of core pressure and a red shift of the spectrum. PMID- 26263314 TI - Exploring Ion-Ion Interactions in Aqueous Solutions by a Combination of Molecular Dynamics and Neutron Scattering. AB - Recent advances in computational and experimental techniques have allowed for accurate description of ion pairing in aqueous solutions. Free energy methods based on ab initio molecular dynamics, as well as on force fields accounting effectively for electronic polarization, can provide quantitative information about the structures and occurrences of individual types of ion pairs. When properly benchmarked against electronic structure calculations for model systems and against structural experiments, in particular neutron scattering, such force field simulations represent a powerful tool for elucidating interactions of salt ions in complex biological aqueous environments. PMID- 26263315 TI - Rotational Doppler Effect: A Probe for Molecular Orbitals Anisotropy. AB - The vibrationally resolved X-ray photoelectron spectra of X2Sigmag+(3sigmag-1) and B2Sigmau+(2sigmau-1) states of N2+ were recorded for different photon energies and orientations of the polarization vector. Clear dependencies of the spectral line widths on the X-ray polarization as well as on the symmetry of the final electronic states are observed. Contrary to the translational Doppler, the rotational Doppler broadening is sensitive to the photoelectron emission anisotropy. On the basis of theoretical modeling, we suggest that the different rotational Doppler broadenings observed for gerade and ungerade final states result from a Young's double-slit interference phenomenon. PMID- 26263316 TI - Solution Synthesis and Optical Properties of Transition-Metal-Doped Silicon Nanocrystals. AB - A new synthetic method was developed to produce a range of transition-metal (Mn, Ni, and Cu) doped silicon nanocrystals (Si NCs). The synthesis produces monodisperse undoped and doped Si NCs with comparable average sizes as shown by transmission electron microscopy (TEM). Dopant composition was confirmed by EDX (energy dispersive X-ray spectroscopy). The optical properties of undoped and doped were compared and contrasted using absorption (steady-state and transient) and photoluminescence spectroscopy. Doped Si NCs demonstrated unique dopant dependent optical properties compared to undoped Si NCs such as enhanced subgap absorption, and 40 nm shifts in the emission. Transient absorption (TA) measurements showed that photoexcitations in doped Si NCs relaxed via dopant states not present in undoped Si NCs. PMID- 26263317 TI - Two-Dimensional Metal Dichalcogenides and Oxides for Hydrogen Evolution: A Computational Screening Approach. AB - We explore the possibilities of hydrogen evolution by basal planes of 2D metal dichalcogenides and oxides in the 2H and 1T class of structures using the hydrogen binding energy as a computational activity descriptor. For some groups of systems like the Ti, Zr, and Hf dichalcogenides the hydrogen bonding to the 2H structure is stronger than that to the 1T structure, while for the Cr, Mo, and W dichalcogenides the behavior is opposite. This is rationalized by investigating shifts in the chalcogenide p levels comparing the two structures. We find that usually for a given material only at most one of the two phases will be active for the hydrogen evolution reaction; however, in most cases the two phases are very close in formation energy, opening up the possibility for stabilizing the active phase. The study points to many new possible 2D HER materials beyond the few that are already known. PMID- 26263318 TI - Computational Prediction of Metal Organic Frameworks Suitable for Molecular Infiltration as a Route to Development of Conductive Materials. AB - The development of metal organic frameworks (MOFs) with high porosity, large surface area, and good electrical properties would offer opportunities for producing functionalized porous materials suitable for energy storage, conversion, and utilization. Realizing these applications remains challenging because of the limited numbers of electrically conductive porous MOFs that are known. We apply density functional theory (DFT) to assess a large number of potentially electrically conductive MOFs generated by infiltrating known materials with conjugated and redox-active 7,7,8,8-tetracyanquinododimethane (TCNQ) molecules. DFT results demonstrate that TCNQ coordinating with dimeric Cu paddlewheels can create molecular chains in a variety of MOFs. Several of these materials feature the formation of multiple dimensional conducting chains, making the materials promising for electrical conductivity. PMID- 26263319 TI - Identification of the Excited-State C?C and C?O Modes of trans-beta-Apo-8' carotenal with Transient 2D-IR-EXSY and Femtosecond Stimulated Raman Spectroscopy. AB - Assigning the vibrational modes of molecules in the electronic excited state is often a difficult task. Here we show that combining two nonlinear spectroscopic techniques, transient 2D exchange infrared spectroscopy (T2D-IR-EXSY) and femtosecond stimulated Raman spectroscopy (FSRS), the contribution of the C?C and C?O modes in the excited-state vibrational spectra of trans-beta-apo-8'-carotenal can be unambiguously identified. The experimental results reported in this work confirm a previously proposed assignment based on quantum-chemical calculations and further strengthen the role of an excited state with charge-transfer character in the relaxation pathway of carbonyl carotenoids. On a more general ground, our results highlight the potentiality of nonlinear spectroscopic methods based on the combined use of visible and infrared pulses to correlate structural and electronic changes in photoexcited molecules. PMID- 26263320 TI - Product Branching in the Low Temperature Reaction of CN with Propyne by Chirped Pulse Microwave Spectroscopy in a Uniform Supersonic Flow. AB - A new chirped-pulse/uniform flow (CPUF) spectrometer has been developed and used to determine product branching in a multichannel reaction. With this technique, bimolecular reactions can be initiated in a cold, thermalized, high-density molecular flow and a broadband microwave spectrum acquired for all products with rotational transitions within a chosen frequency window. In this work, the CN + CH3CCH reaction was found to yield HCN via a direct H-abstraction reaction, whereas indirect addition/elimination pathways to HCCCN, CH3CCCN, and CH2CCHCN were also probed. From these observations, quantitative branching ratios were established for all products as 12(5)%, 66(4)%, 22(6)%, and 0(8)% into HCN, HCCCN, CH3CCCN, and CH2CCHCN, respectively. The values are consistent with statistical calculations based on new ab initio results at the CBS-QB3 level of theory. This work is a demonstration of CPUF as a powerful technique for quantitatively determining the branching into polyatomic products from a bimolecular reaction. PMID- 26263321 TI - Elusive Sulfurous Acid: Gas-Phase Basicity and IR Signature of the Protonated Species. AB - The ion corresponding to protonated sulfurous acid, H3SO3(+), has been successfully delivered into the gas phase by electrospray ionization of the solution of a suitable precursor and an in-source fragmentation process. The neutral acid is a highly elusive molecule. However, its gas-phase basicity has been ascertained by means of a kinetic study of proton-transfer reactivity. The structure of the H3SO3(+) sampled ion has been probed by IRMPD spectroscopy in two complementary IR frequency ranges in conjunction with density functional theory calculations and found to conform to a trihydroxosulfonium ion. The characteristic IR signatures may aid in deciphering the presence of this species in extraterrestrial atmospheres. PMID- 26263322 TI - Electron Spin Polarization Transfer to ortho-H2 by Interaction of para-H2 with Paramagnetic Species: A Key to a Novel para -> ortho Conversion Mechanism. AB - We report that at ambient temperature and with 100% enriched para-hydrogen (p-H2) dissolved in organic solvents, paramagnetic spin catalysis of para -> ortho hydrogen conversion is accompanied at the onset by a negative ortho-hydrogen (o H2) proton NMR signal. This novel finding indicates an electron spin polarization transfer, and we show here that this can only occur if the H2 molecule is dissociated upon its transient adsorption by the paramagnetic catalyst. Following desorption, o-H2 is created until the thermodynamic equilibrium is reached. A simple theory confirms that in the presence of a static magnetic field, the hyperfine coupling between unpaired electrons and nuclear spins is responsible for the observed polarization transfer. Owing to the negative electron gyromagnetic ratio, this explains the experimental results and ascertains an as yet unexplored mechanism for para -> ortho conversion. Finally, we show that the recovery of o-H2 magnetization toward equilibrium can be simply modeled, leading to the para -> ortho conversion rate. PMID- 26263323 TI - Illuminating the Interactions between Small Solutes in Liquid Water. PMID- 26263324 TI - Ab Initio Modeling of Bulk and Intragranular Diffusion in Ni Alloys. AB - Knowledge of solid-state and interfacial species diffusion kinetics is of paramount importance for understanding mechanisms of grain boundary (GB) oxidation causing environmental degradation and cracking of Ni-base structural alloys. In this study, first-principles calculations of vacancy-mediated diffusion are performed across a wide series of alloying elements commonly used in Ni-based superalloys, as well as interstitial diffusion of atomic oxygen and sulfur in the bulk, at the (111) surface, ?110? symmetric tilt GBs of Ni corresponding to model low- (Sigma = 3/(111)) and high-energy (Sigma = 9/(221)) GBs. A substantial enhancement of diffusion is found for all species at the high energy GB as compared with the bulk and the low-energy GB, with Cr, Mn, and Ti exhibiting remarkably small activation barriers (<0.1 eV; ~10 times lower than in the bulk). Calculations also show that the bulk diffusion mechanism and kinetics differ for oxygen and sulfur, with oxygen having a faster mobility and preferentially diffusing through the tetrahedral interstitial sites in Ni matrix, where it can be trapped in a local minimum. PMID- 26263325 TI - Anatomy of the Photochemical Reaction: Excited-State Dynamics Reveals the C-H Acidity Mechanism of Methoxy Photo-oxidation on Titania. AB - Light-driven chemical reactions on semiconductor surfaces have potential for addressing energy and pollution needs through efficient chemical synthesis; however, little is known about the time evolution of excited states that determine reaction pathways. Here, we study the photo-oxidation of methoxy (CH3O) derived from methanol on the rutile TiO2(110) surface using ab initio simulations to create a molecular movie of the process. The movie sequence reveals a wealth of information on the reaction intermediates, time scales, and energetics. The reaction is broken in three stages, described by Lewis structures directly derived from the "hole" wave functions that lead to the concept of "photoinduced C-H acidity". The insights gained from this work can be generalized to a set of simple rules that can predict the efficiency of photo-oxidation reactions in reactant-catalyst pairs. PMID- 26263326 TI - Effect of Mesostructured Layer upon Crystalline Properties and Device Performance on Perovskite Solar Cells. AB - One of the most fascinating characteristics of perovskite solar cells (PSCs) is the retrieved obtainment of outstanding photovoltaic (PV) performances withstanding important device configuration variations. Here we have analyzed CH3NH3PbI3-xClx in planar or in mesostructured (MS) configurations, employing both titania and alumina scaffolds, fully infiltrated with perovskite material or presenting an overstanding layer. The use of the MS scaffold induces to the perovskite different structural properties, in terms of grain size, preferential orientation, and unit cell volume, in comparison to the ones of the material grown with no constraints, as we have found out by X-ray diffraction analyses. We have studied the effect of the PSC configuration on photoinduced absorption and time-resolved photoluminescence, complementary techniques that allow studying charge photogeneration and recombination. We have estimated electron diffusion length in the considered configurations observing a decrease when the material is confined in the MS scaffold with respect to a planar architecture. However, the presence of perovskite overlayer allows an overall recovering of long diffusion lengths explaining the record PV performances obtained with a device configuration bearing both the mesostructure and a perovskite overlayer. Our results suggest that performance in devices with perovskite overlayer is mainly ruled by the overlayer, whereas the mesoporous layer influences the contact properties. PMID- 26263327 TI - Femtosecond Nanoplasmonic Dephasing of Individual Silver Nanoparticles and Small Clusters. AB - We present experimental measurements of localized surface plasmon emission from individual silver nanoparticles and small clusters via accurately delayed femtosecond laser pulses. Fourier transform analysis of the nanoplasmonic coherence oscillations reveals different frequency components and dephasing rates for each nanoparticle. We find three different types of behavior: single exponential decay, beating between two frequencies, and beating among three or more frequencies. Our results provide insight into inhomogeneous and homogeneous broadening mechanisms in nanoplasmonic spectroscopy that depend on morphology and nearby neighbors. In addition, we find the optical response of certain pairs of nanoparticles to be at least an order of magnitude more intense than the response of single particles. PMID- 26263328 TI - Capacitive Dark Currents, Hysteresis, and Electrode Polarization in Lead Halide Perovskite Solar Cells. AB - Despite spectacular advances in conversion efficiency of perovskite solar cell many aspects of its operating modes are still poorly understood. Capacitance constitutes a key parameter to explore which mechanisms control particular functioning and undesired effects as current hysteresis. Analyzing capacitive responses allows addressing not only the nature of charge distribution in the device but also the kinetics of the charging processes and how they alter the solar cell current. Two main polarization processes are identified. Dielectric properties of the microscopic dipolar units through the orthorhombic-to tetragonal phase transition account for the measured intermediate frequency capacitance. Electrode polarization caused by interfacial effects, presumably related to kinetically slow ions piled up in the vicinity of the outer interfaces, consistently explain the reported excess capacitance values at low frequencies. In addition, current-voltage curves and capacitive responses of perovskite-based solar cells are connected. The observed hysteretic effect in the dark current originates from the slow capacitive mechanisms. PMID- 26263329 TI - Activation of Graphenic Carbon Due to Substitutional Doping by Nitrogen: Mechanistic Understanding from First Principles. AB - Nitrogen-doped graphene and carbon nanotubes are popularly in focus as metal-free electrocatalysts for oxygen reduction reactions (ORR) central to fuel cells. N doped CNTs have been also reported to chemisorb mutually, promising a route to their robust predetermined assembly into devices and mechanical reinforcements. We propose from first principles a common mechanistic understanding of these two aspects pointing further to a generic chemical activation of carbon atoms due to substitution by nitrogen in experimentally observed configurations. Wannier function based orbital resolved study of mechanisms suggests increase in C-N bond orders in attempt to retain pi-conjugation among carbon atoms, causing mechanical stress and loss of charge neutrality of nitrogen and carbon atoms, which remedially facilitate chemical activation of N-coordinated C atoms, enhancing sharply with increasing coordination to N and proximity to zigzag edges. Activated C atoms facilitate covalent adsorption of radicals in general, diradicals like O2 relevant to ORR, and also other similarly activated C atoms, leading to self-assembly of graphenic nanostructures while remaining inert to ordinary graphenic C atoms. PMID- 26263330 TI - Dissociative Adsorption of O2 on Al(111): The Role of Orientational Degrees of Freedom. AB - The interaction between O2 molecules and Al surfaces has long been poorly understood despite its importance in diverse chemical phenomena. Early experimental investigations of adsorption dynamics indicated that abstraction of a single O atom by the surface, instead of dissociative chemisorption, dominates at low O2 incident kinetic energies. Abstraction of the closer O atom suggests low barrier heights at perpendicular incidence. However, recent measurements suggest that parallel O2 orientations dominate sticking at low energies. We resolve this apparent contradiction by a systematic ab initio embedded correlated wavefunction study of the stereochemistry of O2 reacting with Al(111). We identify two important new details: (i) initially, roughly parallel oxygen molecules tend to tilt upright while approaching the surface, suggesting that the abstraction channel does dominate at low energies and (ii) the reaction channel with the lowest barrier indeed corresponds to a parallel orientation, which ultimately evolves either into dissociative chemisorption or toward abstraction. PMID- 26263331 TI - Employing PEDOT as the p-Type Charge Collection Layer in Regular Organic Inorganic Perovskite Solar Cells. AB - Organic-inorganic halide perovskite solar cells have recently emerged as high performance photovoltaic devices with low cost, promising for affordable large scale energy production, with laboratory cells already exceeding 20% power conversion efficiency (PCE). To date, a relatively expensive organic hole conducting molecule with low conductivity, namely spiro-OMeTAD (2,2',7,7' tetrakis(N,N-di-p-methoxyphenyl-amine) 9,9'- spirobifluorene), is employed widely to achieve highly efficient perovskite solar cells. Here, we report that by replacing spiro-OMeTAD with much cheaper and highly conductive poly(3,4 ethylenedioxythiophene) (PEDOT) we can achieve PCE of up to 14.5%, with PEDOT cast from a toluene based ink. However, the stabilized power output of the PEDOT based devices is only 6.6%, in comparison to 9.4% for the spiro-OMeTAD-based cells. We deduce that accelerated recombination is the cause for this lower stabilized power output and postulate that reduced levels of p-doping are required to match the stabilized performance of Spiro-OMeTAD. The entirely of the materials employed in the perovskite solar cell are now available at commodity scale and extremely inexpensive. PMID- 26263332 TI - Hyperpolarized Water to Study Protein-Ligand Interactions. AB - The affinity between a chosen target protein and small molecules is a key aspect of drug discovery. Screening by popular NMR methods such as Water-LOGSY suffers from low sensitivity and from false positives caused by aggregated or denatured proteins. This work demonstrates that the sensitivity of Water-LOGSY can be greatly boosted by injecting hyperpolarized water into solutions of proteins and ligands. Ligand binding can be detected in a few seconds, whereas about 30 min is usually required without hyperpolarization. Hyperpolarized water also enhances proton signals of proteins at concentrations below 20 MUM so that one can verify in a few seconds whether the proteins remain intact or have been denatured. PMID- 26263333 TI - Comparison of the Performance of CoP-Coated and Pt-Coated Radial Junction n(+)p Silicon Microwire-Array Photocathodes for the Sunlight-Driven Reduction of Water to H2(g). AB - The electrocatalytic performance for hydrogen evolution has been evaluated for radial-junction n(+)p-Si microwire (MW) arrays with Pt or cobalt phosphide, CoP, nanoparticulate catalysts in contact with 0.50 M H2SO4(aq). The CoP-coated (2.0 mg cm(-2)) n(+)p-Si MW photocathodes were stable for over 12 h of continuous operation and produced an open-circuit photovoltage (Voc) of 0.48 V, a light limited photocurrent density (Jph) of 17 mA cm(-2), a fill factor (ff) of 0.24, and an ideal regenerative cell efficiency (etaIRC) of 1.9% under simulated 1 Sun illumination. Pt-coated (0.5 mg cm(-2)) n(+)p-Si MW-array photocathodes produced Voc = 0.44 V, Jph = 14 mA cm(-2), ff = 0.46, and eta = 2.9% under identical conditions. Thus, the MW geometry allows the fabrication of photocathodes entirely comprised of earth-abundant materials that exhibit performance comparable to that of devices that contain Pt. PMID- 26263334 TI - Velocity Map Imaging Study of Charge-Transfer and Proton-Transfer Reactions of CH3 Radicals with H3(.). AB - The velocity map imaging method has been applied to crossed beam studies of charge transfer and proton transfer between methyl (CH3) radicals formed by pyrolysis and H3(+) cations over the collision energy range from 1.2 to 3.4 eV. Vibrational excitation in the H3(+) reactants plays an important role both in promoting endoergic charge transfer and in supplying energy to the products of the proton-transfer reaction. Excited H3(+) reactants with vibrational energy in excess of the barrier lead to energy-resonant charge transfer via long-range collisions. A small fraction of collisions that take place at low impact parameters appear to form charge-transfer products with higher levels of internal excitation. The proton-transfer reaction exhibits direct, stripping-like dynamics. Consistent with the kinematics of proton transfer, incremental kinetic energy supplied to the reactants is strongly directed into product relative kinetic energy, as predicted by the concept of "induced repulsive energy release". PMID- 26263336 TI - Hydrophobic Ambivalence: Teetering on the Edge of Randomness. AB - Processes ranging from oil-water phase separation to the formation of solid clathrate hydrates send mixed messages regarding whether oil molecules hate or love to be surrounded by water. Recent experimental and theoretical results help decipher these mixed messages by illuminating the conditions under which the stability of a hydrophobic contact is expected to exceed thermal energy fluctuations - thus facilitating hydrophobic self-assembly and the emergence of structure from randomness. Important open questions remain regarding the dependence of hydrophobic interactions on molecular size and temperature, as well as the balance of direct and water-mediated interactions. PMID- 26263335 TI - Graphene-Induced Magnetic Anisotropy of a Two-Dimensional Iron Phthalocyanine Network. AB - A single layer of flat-lying iron phthalocyanine (FePc) molecules assembled on graphene grown on Ir(111) preserves the magnetic moment, as deduced by X-ray magnetic circular dichroism from the Fe L2,3 edges. Furthermore, the FePc molecules in contact with the graphene buffer layer exhibit an enhancement of the magnetic anisotropy, with emergence of an in-plane easy magnetic axis, reflected by an increased orbital moment of the FePc molecules in contact with the C atoms in the graphene sheet. The origin of the increased magnetic anisotropy is discussed, considering the absence of electronic state hybridization, and the breaking of symmetry upon FePc adsorption on graphene. PMID- 26263337 TI - Concurrent Effects of Delocalization and Internal Conversion Tune Charge Separation at Regioregular Polythiophene-Fullerene Heterojunctions. AB - Quantum-dynamical simulations are used to investigate the interplay of exciton delocalization and vibronically induced internal conversion processes in the elementary charge separation steps at regioregular donor-acceptor heterojunctions. Ultrafast internal conversion leads to efficient deexcitation within the excitonic and charge transfer manifolds, thus modifying the charge separation dynamics. We address a model donor-acceptor junction representative of regioregular P3HT-PCBM, using high-dimensional quantum dynamics simulations by multiconfigurational methods. While partial trapping into an interfacial charge separated state occurs, long-range charge-separated states are accessed as previously demonstrated in the work of Tamura and Burghardt [J. Am. Chem. Soc. 2013, 135, 16364]. For an H-aggregate type, stacked donor species, the initial bright state undergoes ultrafast internal conversion within the excitonic manifold, creating multiple charge transfer pathways before reaching the lowest energy dark exciton, which is uncoupled from the charge transfer manifold. This process profoundly affects the charge separation mechanism and efficiency. For small energetic offsets between the interfacial excitonic and charge transfer states, a delocalized initial bright state proves less prone to electron-hole capture by the interfacial trap than a localized, vibronic wavepacket close to the interface. For both delocalized and localized initial states, a comparable yield of free carriers is obtained, which is found to be optimal for energetic offsets of the order of the Coulomb barrier to charge separation. Interfacial trapping is significantly reduced as the barrier height decreases with fullerene aggregation. Despite the high-dimensional nature of the system, charge separation is an ultrafast coherent quantum process exhibiting oscillatory features as observed in recent experiments. PMID- 26263338 TI - Ligand Binding to Distinct Sites on Nanocrystals Affecting Energy and Charge Transfer. AB - Hybrid optoelectronic devices are attractive because they offer the promise of low-cost, roll-to-roll fabrication. Despite this, energy transfer between organic and inorganic interfaces is not well understood. Device engineering on this class of solution-processed materials generally focuses on replacing the long insulating ligands with short ones. Here, we show that energy and charge transfer between an inorganic nanocrystal (NC) donor and organic molecular acceptor is acutely sensitive to the chemical moiety linking the two species. Our results reveal that the CdS NCs have distinct binding sites for different chemical species because only resonance energy transfer (RET) is observed for the carboxylic-acid-functionalized ligand, while both RET and charge transfer are observed for the amine-functionalized ligand. We observe that the equilibrium constant for this static quenching term increases with decreasing particle size. This finding offers a new approach in the design of hybrid thin films for devices and NC probes based on RET used for imaging, sensing, signal transduction, and photon management. PMID- 26263339 TI - Significant Chiral Signal Amplification of Langmuir Monolayers Probed by Second Harmonic Generation. AB - With the development of the nonlinear optical technique such as SHG (second harmonic generation), the in situ measurements of the chirality in the monolayers at the air/water interface have become possible. However, when performing the SHG measurement of the chirality in a monolayer, it is still a great challenge to obtain the chiral signals with a good S/N (signal-to-noise) ratio. In this Letter, interfacial assemblies with induced supramolecular chirality were used to amplify the weak chiral SHG signals from the monolayers at the air/water interface. Tetrakis(4-sulfonatophenyl) porphyrin (TPPS) J aggregates were used as the subphase, and when chiral amphiphilic molecules were spread on it, chiral domains of the amphiphile/TPPS J aggregates were formed and then significantly amplified chiral signals that otherwise could not be detected. Moreover, the sign of the DCE (degree of chiral excess) changed with the chirality of the amphiphilic molecules, thus providing a possible way to obtain the absolute chiral information in situ in the monolayers. PMID- 26263340 TI - Ultrafast Population Inversion without the Strong Field Catch: The Parallel Transfer. AB - Quantum systems with sublevel structures, like molecules, prevent full population inversion from one manifold of sublevels to the other using ultrafast resonant pulses. We explain the mechanism by which this population transfer is blocked. We then develop a novel concept of geometric control, assuming full or partial coherent manipulation within the manifolds, and show that by preparing specific coherent superpositions in the initial manifold, full population inversion or full population blockade, that is, laser transparency, can be achieved. By properly choosing the relative phases of the initial state, one can interfere in the stimulated emission process, changing the pattern of Rabi oscillations so that full population inversion to the excited electronic state can be achieved almost regardless of the pulse intensity after a minimal threshold value. This is the basis of a novel control mechanism, termed parallel transfer. PMID- 26263341 TI - Ferroelectric Polarization in CH3NH3PbI3 Perovskite. AB - We report on ferroelectric polarization behavior in CH3NH3PbI3 perovskite in the dark and under illumination. Perovskite crystals with three different sizes of 700, 400, and 100 nm were prepared for piezoresponse force microscopy (PFM) measurements. PFM results confirmed the formation of spontaneous polarization in CH3NH3PbI3 in the absence of electric field, where the size dependency to polarization was not significant. Whereas the photoinduced stimulation was not significant without an external electric field, the stimulated polarization by poling was further enhanced under illumination. The retention of ferroelectric polarization was also observed after removal of the electric field, in which larger crystals showed longer retention behavior compared to the smaller sized one. Additionally, we suggest the effect of perovskite crystal size (morphology) on charge collection at the interface of the ferroelectric material even though insignificant size dependency in electric polarization was observed. PMID- 26263342 TI - An Explanation of the Photoinduced Giant Dielectric Constant of Lead Halide Perovskite Solar Cells. AB - A photoinduced giant dielectric constant of ~10(6) has been found in impedance spectroscopy measurements of lead halide perovskite solar cells. We report similar effects in measurements of a porous lead zirconate titanate (PZT) sample saturated with water. The principal effect of the illumination of the solar cell and of the introduction of water into the pore volume of the PZT sample is a significant increase in conductivity and dielectric loss. This is shown to exhibit low frequency power law dispersion. Application of the Kramers-Kronig relationships show the large measured values of permittivity to be related to the power law changes in conductivity and dielectric loss. The power law dispersions in the electrical responses are consistent with an electrical network model of microstructure. It is concluded that the high apparent values of permittivity are features of the microstructural networks and not fundamental effects in the two perovskite materials. PMID- 26263343 TI - Visualization of Hot Exciton Energy Relaxation from Coherent to Diffusive Regimes in Conjugated Polymers: A Theoretical Analysis. AB - The unified coherent-to-diffusive energy relaxation of hot exciton in organic aggregates or polymers, which still remains largely unclear and is also a great challenge theoretically, is investigated from a time-dependent wavepacket diffusive approach. The results demonstrate that in the multiple time scale energy relaxation dynamics, the fast relaxation time essentially corresponds to the dephasing time of excitonic coherence motion, whereas the slow time is related to a hopping migration, and a suggested kinetic model successfully connects these two processes. The dependencies of those times on the initial energy and delocalization of exciton wavepacket as well as exciton-phonon interactions are further analyzed. The proposed method together with quantum chemistry calculations has explained an experimental observation of hot exciton energy relaxation in the low-bandgap copolymer PBDTTPD. PMID- 26263344 TI - Charge-State Control of Mn(2+) Spin Relaxation Dynamics in Colloidal n-Type Zn1 xMnxO Nanocrystals. AB - Colloidal diluted magnetic semiconductor (DMS) nanocrystals are model systems for studying spin effects in semiconductor nanostructures with relevance to future spin-based information processing technologies. The introduction of excess delocalized charge carriers into such nanocrystals turns on strong dopant-carrier magnetic exchange interactions, with important consequences for the physical properties of these materials. Here, we use pulsed electron paramagnetic resonance (pEPR) spectroscopy to probe the effects of excess conduction band electrons on the spin dynamics of colloidal Mn(2+)-doped ZnO nanocrystals. Mn(2+) spin-lattice relaxation is strongly accelerated by the addition of even one conduction band electron per Zn1-xMnxO nanocrystal, attributable to the introduction of a new exchange-based Mn(2+) spin relaxation pathway. A kinetic model is used to describe the enhanced relaxation rates, yielding new insights into the spin dynamics and electronic structures of these materials with potential ramifications for future applications of DMS nanostructures in spin based technologies. PMID- 26263346 TI - Effect of Water Hydrogen Bonding on the Solvent-Mediated "Oscillatory" Repulsion of C60 Fullerenes in Water. AB - The solvent-mediated interaction of C60 fullerenes in liquid water is examined by using the combination of the probabilistic hydrogen bond model with the density functional theory. This combination allows one to take into account the effect of hydrogen bonding between water molecules on their interaction with fullerenes and to construct an approximation for the distribution of water molecules in the system, which provides an efficient foundation for studying hydrophobic phenomena. Our numerical evaluations predict the solvent-induced interaction of two C60 fullerenes in water at 293 K to have an oscillatory-repulsive character (previously observed in molecular dynamics simulations) only when the vicinal water-water hydrogen bonds are slightly weaker than bulk ones. Besides indicating the direction of the energetic alteration of water-water hydrogen bonds near C60 fullerenes, our model also suggests that the hydrogen bonding ability of water plays a defining role in the solvent-mediated C60-C60 repulsion. PMID- 26263345 TI - Power-Law Solvation Dynamics in G-Quadruplex DNA: Role of Hydration Dynamics on Ligand Solvation inside DNA. AB - G-quadruplex DNA (GqDNA) structures act as promising anticancer targets for small molecules (ligands). Solvation dynamics of a ligand (DAPI: 4',6-diamidino-2 phenylindole) inside antiparallel-GqDNA is studied through direct comparison of time-resolved experiments to molecular dynamics (MD) simulation. Dynamic Stokes shifts of DAPI in GqDNA prepared in H2O buffer and D2O are compared to find the effect of water on ligand solvation. Experimental dynamics (in H2O) is then directly compared with the dynamics computed from 65 ns simulation on the same DAPI-GqDNA complex. Ligand solvation follows power-law relaxation (summed with fast exponential relaxation) from ~100 fs to 10 ns. Simulation results show relaxation below ~5 ps is dominated by water motion, while both water and DNA contribute comparably to dictate long-time power-law dynamics. Ion contribution is, however, found to be negligible. Simulation results also suggest that anomalous solvation dynamics may have origin in subdiffusive motion of perturbed water near GqDNA. PMID- 26263347 TI - Macrocrystals of Colloidal Quantum Dots in Anthracene: Exciton Transfer and Polarized Emission. AB - In this work, centimeter-scale macrocrystals of nonpolar colloidal quantum dots (QDs) incorporated into anthracene were grown for the first time. The exciton transfer from the anthracene host to acceptor QDs was systematically investigated, and anisotropic emission from the isotropic QDs in the anthracene macrocrystals was discovered. Results showed a decreasing photoluminescence lifetime of the donor anthracene, indicating a strengthening energy transfer with increasing QD concentration in the macrocrystals. With the anisotropy study, QDs inside the anthracene host acquired a polarization ratio of ~1.5 at 0 degrees collection angle, and this increases to ~2.5 at the collection angle of 60 degrees . A proof-of-concept application of these excitonic macrocrystals as tunable color converters on light-emitting diodes was also demonstrated. PMID- 26263348 TI - A Switchable High-Sensitivity Photodetecting and Photovoltaic Device with Perovskite Absorber. AB - Amplified photocurrent gain has been obtained by photodiodes of inorganic semiconductors such as GaAs and Si. The avalanche photodiode, developed for high sensitivity photodetectors, requires an expensive vapor-phase epitaxy manufacture process and high driving voltage (50-150 V). Here, we show that a low-cost solution-processed device using a planar-structured ferroelectric organo-lead triiodide perovskite enables light detection in a large dynamic range of incident power (10(-7)-10(-1) W cm(-2)) by switching with small voltage (-0.9 to +0.5 V). The device achieves significantly high external quantum conversion efficiency (EQE) up to 2.4 * 10(5)% (gain value of 2400) under weak monochromatic light. On a single dual-functional device, incident small power (0.2-100 MUW cm(-2)) and medium to large power (>0.1 mW cm(-2)) are captured by reverse bias and forward bias modes, respectively, with linear responsivity of current. For weak light detection, the device works with a high responsivity value up to 620 A W(-1). PMID- 26263349 TI - Orientation-Dependent Interaction between CO2 Molecules Adsorbed on Ru(0001). AB - Determining the molecular structure of CO2 adsorbed on metal surfaces and its mutual interactions is important to understand its catalytic conversion reactions. Here, we study CO2 adsorption on Ru(0001) using scanning tunneling microscopy (STM) and density functional theory (DFT) calculations. Adsorbed at 77 K, the CO2 molecules form mainly disordered structures at submonolayer coverage, except for small (2 * 2) domains. The adsorbed molecules are no longer linear as in the gas phase, but instead, they adopt a "V"-shape geometry with the carbon atom occupying three-fold hcp hollow sites and possess three symmetry-equivalent orientations. Annealing to 250 K causes partial desorption of the molecules, while the remaining molecules form trimers of three different configurations with different interaction energies determined by their relative orientations. The "strong"-interacting trimer shows a cyclic structure, about 40 meV more stable than the "weak"-interacting trimer that is composed of three parallel molecules. PMID- 26263350 TI - Ab Initio Approach for Prediction of Oxide Surface Structure, Stoichiometry, and Electrocatalytic Activity in Aqueous Solution. AB - The design of efficient, stable, and inexpensive catalysts for oxygen evolution and reduction is crucial for the development of electrochemical energy conversion devices such as fuel cells and metal-air batteries. Currently, such design is limited by challenges in atomic-scale experimental characterization and computational modeling of solid-liquid interfaces. Here, we begin to address these issues by developing a general-, first-principles-, and electrochemical principles-based framework for prediction of catalyst surface structure, stoichiometry, and stability as a function of pH, electrode potential, and aqueous cation concentration. We demonstrate the approach by determining the surface phase diagram of LaMnO3, which has been studied for oxygen evolution and reduction and computing the reaction overpotentials on the relevant surface phases. Our results illustrate the critical role of solvated cation species in governing the catalyst surface structure and stoichiometry, and thereby catalytic activity, in aqueous solution. PMID- 26263352 TI - Severe oropharyngitis due to herpes simplex virus type 2 infection in an immunocompetent adult. PMID- 26263353 TI - An unusual cause of a rectal mass: a malpositioned pessary. PMID- 26263354 TI - Adenomyoma of the duodenum. PMID- 26263355 TI - Recurrent pancreatitis in a patient with choledochal cyst and anomalous pancreaticobiliary junction. PMID- 26263356 TI - Video of the month: crowbar endoscopic enucleation of a giant appendicolith. PMID- 26263361 TI - About TMPRSS6 rs855791 polymorphism, iron metabolism and celiac disease. PMID- 26263362 TI - Levels of fecal calprotectin and the severity of postoperative patients with Crohn's disease. PMID- 26263363 TI - Response to Zanella et al. PMID- 26263364 TI - The utility of C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin and fecal lactoferrin to exclude inflammatory bowel disease in adults with IBS. PMID- 26263365 TI - Response to Dai et al. PMID- 26263366 TI - Response to Dai et al. PMID- 26263367 TI - Cannabinoid receptor agonist namisol does not affect cytokine levels in chronic pancreatitis patients. PMID- 26263368 TI - Response to Utomo et al. PMID- 26263369 TI - Incidence of microscopic colitis in relation to the number of colonoscopies over time. PMID- 26263370 TI - Response to Masclee et al. PMID- 26263372 TI - Pacing Strategy, Muscle Fatigue, and Technique in 1500-m Speed-Skating and Cycling Time Trials. AB - PURPOSE: To evaluate pacing behavior and peripheral and central contributions to muscle fatigue in 1500-m speed-skating and cycling time trials when a faster or slower start is instructed. METHODS: Nine speed skaters and 9 cyclists, all competing at regional or national level, performed two 1500-m time trials in their sport. Athletes were instructed to start faster than usual in 1 trial and slower in the other. Mean velocity was measured per 100 m. Blood lactate concentrations were measured. Maximal voluntary contraction (MVC), voluntary activation (VA), and potentiated twitch (PT) of the quadriceps muscles were measured to estimate central and peripheral contributions to muscle fatigue. In speed skating, knee, hip, and trunk angles were measured to evaluate technique. RESULTS: Cyclists showed a more explosive start than speed skaters in the fast start time trial (cyclists performed first 300 m in 24.70 +/- 1.73 s, speed skaters in 26.18 +/- 0.79 s). Both trials resulted in reduced MVC (12.0% +/- 14.5%), VA (2.4% +/- 5.0%), and PT (25.4% +/- 15.2%). Blood lactate concentrations after the time trial and the decrease in PT were greater in the fast-start than in the slow-start trial. Speed skaters showed higher trunk angles in the fast-start than in the slow-start trial, while knee angles remained similar. CONCLUSIONS: Despite similar instructions, behavioral adaptations in pacing differed between the 2 sports, resulting in equal central and peripheral contributions to muscle fatigue in both sports. This provides evidence for the importance of neurophysiological aspects in the regulation of pacing. It also stresses the notion that optimal pacing needs to be studied sport specifically, and coaches should be aware of this. PMID- 26263373 TI - Differential Effect of Viral Hepatitis Infection on Mortality among Korean Maintenance Dialysis Patients: A Prospective Multicenter Cohort Study. AB - The role of infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) in terms of survival among dialysis patients remains incompletely understood. In the present multicenter prospective cohort study, we investigated the prevalences of HBV and HCV infection among 3,321 patients receiving maintenance dialysis in Korea, and assessed the impacts of these infections on survival. All included patients underwent hepatitis B antigen (HBsAg) and HCV antibody (Ab) testing, which revealed that 236 patients (7.1%) were HBsAg-positive, and 123 patients (3.7%) were HCV Ab-positive. HBsAg-positive and HCV Ab-positive patients were matched to hepatitis virus-negative patients using a propensity score at a ratio of 1:2. The prevalences of HBV and HCV infection did not significantly differ according to dialysis modality. Linear-by-linear association analysis revealed that hepatitis B prevalence significantly increased with increasing dialysis vintage (p = 0.001), and hepatitis C prevalence tended to be higher with increasing dialysis vintage (p = 0.074). We compared the survival of HBsAg positive and HCV Ab-positive patients to that of hepatitis virus-negative patients. After propensity score matching, cumulative survival did not differ between HBsAg-positive and HBsAg-negative patients (p = 0.37), while HCV Ab positive patients showed significantly lower survival than HCV Ab-negative patients (p = 0.03). The main conclusions of the present study are that HBV infection prevalence increased with longer dialysis vintage, and that both HBV and HCV infections were most prevalent among patients with the longest dialysis vintage. Additionally, HCV infection among maintenance dialysis patients is associated with an increased risk of mortality. PMID- 26263375 TI - Development of the Final Version of the Classification and Assessment of Occupational Dysfunction Scale. AB - Occupational therapy is involved in disability prevention and health enhancement through the prevention of occupational dysfunction. Although many occupational dysfunction scales exist, no standard method is available for the assessment and classification of occupational dysfunction, which may include occupational imbalance, occupational deprivation, occupational alienation, and occupational marginalization. The purpose of this study was to develop the final version of Classification and Assessment of Occupational Dysfunction (CAOD). Our study demonstrated the validity and reliability of CAOD in a group of undergraduate students. The CAOD scale includes 16 items and addresses the following 4 domains: occupational imbalance, occupational deprivation, occupational alienation, and occupational marginalization. PMID- 26263374 TI - E3 Ubiquitin Ligase NEDD4 Promotes Influenza Virus Infection by Decreasing Levels of the Antiviral Protein IFITM3. AB - Interferon (IFN)-induced transmembrane protein 3 (IFITM3) is a cell-intrinsic factor that limits influenza virus infections. We previously showed that IFITM3 degradation is increased by its ubiquitination, though the ubiquitin ligase responsible for this modification remained elusive. Here, we demonstrate that the E3 ubiquitin ligase NEDD4 ubiquitinates IFITM3 in cells and in vitro. This IFITM3 ubiquitination is dependent upon the presence of a PPxY motif within IFITM3 and the WW domain-containing region of NEDD4. In NEDD4 knockout mouse embryonic fibroblasts, we observed defective IFITM3 ubiquitination and accumulation of high levels of basal IFITM3 as compared to wild type cells. Heightened IFITM3 levels significantly protected NEDD4 knockout cells from infection by influenza A and B viruses. Similarly, knockdown of NEDD4 in human lung cells resulted in an increase in steady state IFITM3 and a decrease in influenza virus infection, demonstrating a conservation of this NEDD4-dependent IFITM3 regulatory mechanism in mouse and human cells. Consistent with the known association of NEDD4 with lysosomes, we demonstrate for the first time that steady state turnover of IFITM3 occurs through the lysosomal degradation pathway. Overall, this work identifies the enzyme NEDD4 as a new therapeutic target for the prevention of influenza virus infections, and introduces a new paradigm for up-regulating cellular levels of IFITM3 independently of IFN or infection. PMID- 26263376 TI - Lyso-Sulfatide Binds Factor Xa and Inhibits Thrombin Generation by the Prothrombinase Complex. AB - Blood coagulation reactions are strongly influenced by phospholipids, but little is known about the influence of sphingolipids on coagulation mechanisms. Lysosulfatide (lyso-SF) (sulfogalactosyl sphingosine) prolonged factor Xa (fXa) 1 stage plasma clotting assays, showing it had robust anticoagulant activity. In studies using purified clotting factors, lyso-SF inhibited >90% of prothrombin (II) activation for reaction mixtures containing fXa/factor Va (fVa)/II, and also inhibited II activation generation by fXa/ phospholipids and by Gla-domainless fXa/fVa/phospholipids. When lyso-SF analogs were tested, results showed that N acetyl-sulfatide was not anticoagulant, implying that the free amine group was essential for the anticoagulant effects of lyso-SF. Lyso-SF did not inhibit fXa enzymatic hydrolysis of small peptide substrates, showing it did not directly inhibit the fXa activity. In surface plasmon resonance studies, lyso-SF bound to immobilized inactivated fXa as well as inactivated Gla-domainless-fXa. Confirming this lyso-SF:fXa interaction, fluorescence studies showed that fluorescently labeled-fXa in solution bound to lyso-SF. Thus, lyso-SF is an anticoagulant lipid that inhibits fXa when this enzyme is bound to either phospholipids or to fVa. Mechanisms for inhibition of procoagulant activity are likely to involve lyso-SF binding to fXa domain(s) that are distinct from the fXa Gla domain. This suggests that certain sphingolipids, including lyso-SF and some of its analogs, may down regulate fXa activity without inhibiting the enzyme's active site or binding to the fXa Gla domain. PMID- 26263378 TI - Fate of Soil Organic Carbon and Polycyclic Aromatic Hydrocarbons in a Vineyard Soil Treated with Biochar. AB - The effect of biochar addition on the levels of black carbon (BC) and polcyclic aromatic hydrocarbons (PAHs) in a vineyard soil in central Italy was investigated within a two year period. Hydropyrolysis (HyPy) was used to determine the contents of BC (BCHyPy) in the amended and control soils, while the hydrocarbon composition of the semi-labile (non-BCHyPy) fraction released by HyPy was determined by gas chromatography-mass spectrometry, together with the solvent extractable PAHs. The concentrations of these three polycyclic aromatic carbon reservoirs changed and impacted differently the soil organic carbon over the period of the trial. The addition of biochar (33 ton dry biochar ha(-1)) gave rise to a sharp increase in soil organic carbon, which could be accounted for by an increase in BCHyPy. Over time, the concentration of BCHyPy decreased significantly from 36 to 23 mg g(-1) and as a carbon percentage from 79% to 61%. No clear time trends were observed for the non-BCHyPy PAHs varying from 39 to 34 MUg g(-1) in treated soils, not significantly different from control soils. However, the concentrations of extractable PAHs increased markedly in the amended soils and decreased with time from 153 to 78 ng g(-1) remaining always higher than those in untreated soil. The extent of the BCHyPy loss was more compatible with physical rather than chemical processes. PMID- 26263377 TI - Promoter Hypomethylation of Maspin Inhibits Migration and Invasion of Extravillous Trophoblast Cells during Placentation. AB - OBJECTIVE: Extravillous trophoblast (EVT) cells invade the endometrium and the maternal spiral arterioles during the first trimester. Mammary Serine Protease Inhibitor (Maspin, SERPINB5) plays a putative role in regulating the invasive activity of cytotrophoblasts. The maspin gene is silenced in various cancers by an epigenetic mechanism that involves aberrant cytosine methylation. We investigated the effect of the methylation status of the maspin promoter on the maspin expression and the aggressiveness of EVT cells. METHODS: Western blotting was used to detect the maspin protein expression in EVT cells upon hypoxia. The proliferative ability, the apoptosis rate and the migration and invasiveness were measured with Cell Counting Kit-8 assay, Flow Cytometry technology and Transwell methods. Subsequently, we treated cells with recombinant maspin protein. The methylation degree of maspin promoter region upon hypoxia/ decitabine was detected by bisulfite sequencing PCR and methylation-specific PCR. Finally, we explored the effects of decitabine on maspin protein expression and the aggressiveness of EVT cells. RESULTS: Hypoxia effectively increased maspin protein expression in EVT cells and significantly inhibited their aggressiveness. The addition of recombinant maspin protein inhibited this aggressiveness. Decitabine reduced the methylation in the maspin promoter region and effectively increased the maspin protein expression, which significantly weakened the migration and invasiveness of EVT cells. DISCUSSION: The methylation status of the maspin promoter is an important factor that affects the migration and invasion of EVT cells during early pregnancy. A decrease in the methylation status can inhibit the migration and invasion of EVT cells to affect placentation and can result in the ischemia and hypoxia of placenta. PMID- 26263380 TI - Executive functioning in schizophrenia: Unique and shared variance with measures of fluid intelligence. AB - OBJECTIVE: Patients with schizophrenia often display deficits on tasks thought to measure "executive" processes. Recently, it has been suggested that reductions in fluid intelligence test performance entirely explain deficits reported for patients with focal frontal lesions on classical executive tasks. For patients with schizophrenia, it is unclear whether deficits on executive tasks are entirely accountable by fluid intelligence and representative of a common general process or best accounted for by distinct contributions to the cognitive profile of schizophrenia. METHOD: In the current study, 50 patients with schizophrenia and 50 age, sex and premorbid intelligence matched controls were assessed using a broad neuropsychological battery, including tasks considered sensitive to executive abilities, namely the Hayling Sentence Completion Test (HSCT), word fluency, Stroop test, digit-span backwards, and spatial working memory. Fluid intelligence was measured using both the Matrix reasoning subtest from the Weschler Abbreviated Scale of Intelligence (WASI) and a composite score derived from a number of cognitive tests. RESULTS: Patients with schizophrenia were impaired on all cognitive measures compared with controls, except smell identification and the optimal betting and risk-taking measures from the Cambridge Gambling Task. After introducing fluid intelligence as a covariate, significant differences remained for HSCT suppression errors, and classical executive function tests such as the Stroop test and semantic/phonemic word fluency, regardless of which fluid intelligence measure was included. CONCLUSIONS: Fluid intelligence does not entirely explain impaired performance on all tests considered as reflecting "executive" processes. For schizophrenia, these measures should remain part of a comprehensive neuropsychological assessment alongside a measure of fluid intelligence. PMID- 26263379 TI - Targeting the NF-kappaB Pathway as a Combination Therapy for Advanced Thyroid Cancer. AB - NF-kappaB signaling plays an important role in tumor cell proliferation, cell survival, angiogenesis, invasion, metastasis and drug/radiation resistance. Combination therapy involving NF-kappaB pathway inhibition is an attractive strategy for the treatment of advanced forms of thyroid cancer. This study was designed to test the efficacy of NF-kappaB pathway inhibition in combination with cytotoxic chemotherapy, using docetaxel and ionizing radiation in in vitro models of thyroid cancer. We found that while both docetaxel and ionizing radiation activated NF-kappaB signaling in thyroid cancer cells, there was no synergistic effect on cell proliferation and/or programmed cell death with either genetic (transduction of a dominant negative mutant form of IkappaBalpha) or pharmacologic (proteasome inhibitor bortezomib and IKKbeta inhibitor GO-Y030) inhibition of the NF-kappaB pathway in thyroid cancer cell lines BCPAP, 8505C, THJ16T and SW1736. Docetaxel plus bortezomib synergistically decreased in vitro invasion of 8505C cells, but not in the other cell lines. Screening of a panel of clinically relevant targeted therapies for synergy with genetic NF-kappaB inhibition in a proliferation/cytotoxicity assay identified the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) as a potential candidate. However, the synergistic effect was confirmed only in the BCPAP cells. These results indicate that NF-kappaB inhibitors are unlikely to be beneficial as combination therapy with taxane cytotoxic chemotherapy, external radiation therapy or radioiodine therapy. There may be unique circumstances where NF-kappaB inhibitors may be considered in combination with docetaxel to reduce tumor invasion or in combination with HDAC inhibitors to reduce tumor growth, but this does not appear to be a combination therapy that could be broadly applied to patients with advanced thyroid cancer. Further research may identify which subsets of patients/tumors may respond to this therapeutic approach. PMID- 26263382 TI - Effects of invalid feedback on learning and feedback-related brain activity in decision-making. AB - For adaptive decision-making it is important to utilize only relevant, valid and to ignore irrelevant feedback. The present study investigated how feedback processing in decision-making is impaired when relevant feedback is combined with irrelevant and potentially invalid feedback. We analyzed two electrophysiological markers of feedback processing, the feedback-related negativity (FRN) and the P300, in a simple decision-making task, in which participants processed feedback stimuli consisting of relevant and irrelevant feedback provided by the color and meaning of a Stroop stimulus. We found that invalid, irrelevant feedback not only impaired learning, it also altered the amplitude of the P300 to relevant feedback, suggesting an interfering effect of irrelevant feedback on the processing of relevant feedback. In contrast, no such effect on the FRN was obtained. These results indicate that detrimental effects of invalid, irrelevant feedback result from failures of controlled feedback processing. PMID- 26263381 TI - Enhancing both motor and cognitive functioning in Parkinson's disease: Aerobic exercise as a rehabilitative intervention. AB - BACKGROUND: Aerobic exercise training (AET) has been shown to provide health benefits in individuals with Parkinson's disease (PD). However, it is yet unknown to what extent AET also improves cognitive and procedural learning capacities, which ensure an optimal daily functioning. OBJECTIVE: In the current study, we assessed the effects of a 3-month AET program on executive functions (EF), implicit motor sequence learning (MSL) capacity, as well as on different health related outcome indicators. METHODS: Twenty healthy controls (HC) and 19 early PD individuals participated in a supervised, high-intensity, stationary recumbent bike-training program (3 times/week for 12 weeks). Exercise prescription started at 20 min (+5 min/week up to 40 min) based on participant's maximal aerobic power. Before and after AET, EF tests assessed participants' inhibition and flexibility functions, whereas implicit MSL capacity was evaluated using a version of the Serial Reaction Time Task. RESULTS: The AET program was effective as indicated by significant improvement in aerobic capacity in all participants. Most importantly, AET improved inhibition but not flexibility, and motor learning skill, in both groups. CONCLUSION: Our results suggest that AET can be a valuable non-pharmacological intervention to promote physical fitness in early PD, but also better cognitive and procedural functioning. PMID- 26263383 TI - Between Bouillaud and Broca: An unknown Italian debate on cerebral localization of language. AB - From 1825 onward, Bouillaud began gathering clinical evidence to support the hypothesis that speech is located in the cerebral frontal lobes. His aim was to provide empirical proof to Gall's theory of a specific substratum of speech in the anterior region of the brain. A well-known discussion ensued inside the French school among supporters and detractors that went far beyond Broca's first report in 1861. Unknown is that Bouillaud's investigations on localization of articulated language also gave rise to a discussion in Italy in the same period. In particular, speech localization formed a central topic in the mid-19th century in Northern Italy mainly thanks to four physicians, Michelangelo Asson, Mose Rizzi, Gaetano Strambio and Filippo Lussana, who reported on language-impaired patients and approached these cases in the light of Bouillaud's claims. Similarly to the French debate, the Italian medical community also included attacks and advocacies of the hypothesis of a precise localization of articulated language in the frontal lobes. However, they were mainly interested in investigating the anatomo-clinical relationships rather than in supporting Gall's organology. This Italian debate appears to be the first to have developed in the mid-19th century outside that of the French community. PMID- 26263385 TI - Surface Behavior of Boronic Acid-Terminated Silicones. AB - Silicone polymers, with their high flexibility, lie in a monolayer at the air water interface as they are compressed until a critical pressure is reached, at which point multilayers are formed. Surface pressure measurements demonstrate that, in contrast, silicones that are end-modified with polar groups take up lower surface areas under compression because the polar groups submerge into the water phase. Boronic acids have the ability to undergo coordination with Lewis bases. As part of a program to examine the surface properties of boronic acids, we have prepared boronic acid-modified silicones (SiBAs) and examined them at the air-water interface to better understand if they behave like other end-functional silicones. Monolayers of silicones, aminopropylsilicones, and SiBAs were characterized at the air-water interface as a function of end functionalization and silicone chain length. Brewster angle and atomic force microscopies confirm domain formation and similar film morphologies for both functionalized and non functionalized silicone chains. There is a critical surface pressure (10 mN m( 1)) independent of chain length that corresponds to a first-order phase transition. Below this transition, the film appears to be a homogeneous monolayer, whose thickness is independent of the chain length. Ellipsometry at the air-water interface indicates that the boronic acid functionality leads to a significant increase of film thickness at low molecular areas that is not seen for non-functionalized silicone chains. What differentiates the boronic acids from simple silicones or other end-functionalized silicones, in particular, is the larger area occupied by the headgroup when under compression compared to other or non-end-functionalized silicones, which suggests an in-plane rather than submerged orientation that may be driven by boronic acid self-complexation. PMID- 26263386 TI - Moving Focus from Weight to Health. What Are the Components Used in Interventions to Improve Cardiovascular Health in Children? AB - INTRODUCTION: Obesity in childhood impacts on many areas of the child's current and future health, including their cardiovascular health. To date many attempts have been made to design interventions to tackle excess childhood weight but with limited success. We aimed to establish the components common to interventions in children that improve cardiovascular health parameters. METHODS: We searched the following databases: EMBASE 1974-week 3 November 2014, Ovid Medline 1946 Present, and PsychINFO 1967-Present for studies reporting interventions in healthy young people under the age of 18. Included interventions had to contain an education component and have been carried out in a community, school, or clinical setting. Papers had to report on at least one of the pre-specified CVD risk parameters and at least one non-biological outcome from knowledge, attitudes or behaviours. RESULTS: We retrieved 2451 papers, from which 12 studies (18 papers) of 3046 participants were included. From the selected papers we identified four component themes; Health Behaviours, Self-Concept, Practical and Cognitive Tools, and Intervention Characteristics. The subcomponents that made up these themes were fairly consistent across the studies analysed although the studies varied in their duration, settings and children with which they were carried out. Nine of the studies were able to bring about positive change in at least one biological and one non-biological aspect of child cardiovascular health. CONCLUSION: The component themes identified here were common to intervention studies that had success in improving parameters of cardiovascular health. We suggest that the focus of childhood health interventions be moved from weight onto cardiovascular health parameters and that future interventions use the lessons learned by their predecessors to incorporate those components that are associated with successful interventions. PMID- 26263384 TI - KSHV MicroRNAs Repress Tropomyosin 1 and Increase Anchorage-Independent Growth and Endothelial Tube Formation. AB - Kaposi's sarcoma (KS) is characterized by highly vascularized spindle-cell tumors induced after infection of endothelial cells by Kaposi's sarcoma-associated herpesvirus (KSHV). In KS tumors, KSHV expresses only a few latent proteins together with 12 pre-microRNAs. Previous microarray and proteomic studies predicted that multiple splice variants of the tumor suppressor protein tropomyosin 1 (TPM1) were targets of KSHV microRNAs. Here we show that at least two microRNAs of KSHV, miR-K2 and miR-K5, repress protein levels of specific isoforms of TPM1. We identified a functional miR-K5 binding site in the 3' untranslated region (UTR) of one TPM1 isoform. Furthermore, the inhibition or loss of miR-K2 or miR-K5 restores expression of TPM1 in KSHV-infected cells. TPM1 protein levels were also repressed in KSHV-infected clinical samples compared to uninfected samples. Functionally, miR-K2 increases viability of unanchored human umbilical vein endothelial cells (HUVEC) by inhibiting anoikis (apoptosis after cell detachment), enhances tube formation of HUVECs, and enhances VEGFA expression. Taken together, KSHV miR-K2 and miR-K5 may facilitate KSHV pathogenesis. PMID- 26263388 TI - Right-Side Colon Ischemia: Clinical Features, Large Visceral Artery Occlusion, and Long-Term Follow-Up. AB - CONTEXT: Large visceral artery occlusion (LVAO) could underlie right-side colon ischemia (RSCI) but is little known. OBJECTIVE: To assess patients with RSCI through long-term follow-up, including features and management of LVAO. MAIN OUTCOME MEASURES: Mesenteric ischemia and mortality. DESIGN: Retrospective observational study in an integrated health care system. RESULTS: Of 49 patients (30 women [61.2%]; mean [standard deviation] age, 69.4 [11.9] years), 19 (38.8%) underwent surgery-that is, 5 (83.3%) of 6 who developed RSCI in hospital following surgical procedures and 14 (32.6%) of 43 who had RSCI before hospitalization (p value = 0.03); overall, 5 (10.2%) died. Among 44 survivors with a median (range) follow-up of 5.19 (0.03-14.26) years, 5 (11.4%), including 3 (20.0%) of 15 operated cases, had symptomatic LVAO and underwent angioplasty and stent placement: 2 for abdominal angina that preceded RSCI, 1 for acute mesenteric ischemia 1 week after resection of RSCI, 1 for RSCI 6 weeks after resection of left-side ischemia, and 1 for abdominal angina that began 3 years after spontaneous recovery from RSCI. None had further mesenteric ischemia until death from nonintestinal disease or the end of follow-up (1.6 to 10.2 years later). Kaplan-Meier survival estimates for all 44 survivors at 1, 3, 5, and 10 years were 88.6%, 72.3%, 57.6%, and 25.9%, respectively. Thirty-one patients (70.4%) died during follow-up, 19 (61.3%) of a known cause; the 39 patients not treated for LVAO lacked mesenteric ischemia. CONCLUSION: Patients with RSCI may have symptomatic LVAO; therefore, we advise they undergo careful query for symptoms of abdominal angina and routine visceral artery imaging. PMID- 26263387 TI - Novel Epigenetic CREB-miR-630 Signaling Axis Regulates Radiosensitivity in Colorectal Cancer. AB - BACKGROUND: miR-630 has been reported to be a modulator of several cancers, but the mechanism by which is it influences radioresistance remains unknown. We aimed to identify the molecular function of miR-630 and its regulatory mechanism in colorectal cancer (CRC) cell lines. METHODOLOGY: Overexpression and loss-of function analyses of miR-630 were performed in CRC cell lines by measuring their levels of growth and apoptosis after ionic radiation (IR). Target genes were detected via a dual-luciferase assay and Western blot. Chromatin immunoprecipitation assay was carried out to identify the transcription factor regulating miR-630, and a demethylation experiment was also conducted. RESULTS: miR-630 expression was found to be positively correlated with radiosensitivity in CRC cell lines (p<0.05). After IR treatment, miR-630 induced apoptosis in cells; however, the opposite was observed when miR-630 was downregulated (p<0.05). BCL2L2 and TP53RK were identified as the target genes of miR-630, and the function of miR-630 was found to depend on these two genes (p<0.05). In addition, evidence showed that CREB regulates the level of miR-630, and demethylation can elevate miR-630 levels (p<0.05). CONCLUSION: CREB-miR-630-BCL2L2 and TP53RK comprise a novel signaling cascade regulating radiosensitivity in CRC cell lines by inducing cell apoptosis and death. PMID- 26263389 TI - Incentive-Based Primary Care: Cost and Utilization Analysis. AB - CONTEXT: In its fee-for-service funding model for primary care, British Columbia, Canada, introduced incentive payments to general practitioners as pay for performance for providing enhanced, guidelines-based care to patients with chronic conditions. Evaluation of the program was conducted at the health care system level. OBJECTIVE: To examine the impact of the incentive payments on annual health care costs and hospital utilization patterns in British Columbia. DESIGN: The study used Ministry of Health administrative data for Fiscal Year 2010-2011 for patients with diabetes, congestive heart failure, chronic obstructive pulmonary disease, and/or hypertension. In each disease group, cost and utilization were compared across patients who did, and did not, receive incentive-based care. MAIN OUTCOME MEASURES: Health care costs (eg, primary care, hospital) and utilization measures (eg, hospital days, readmissions). RESULTS: After controlling for patients' age, sex, service needs level, and continuity of care (defined as attachment to a general practice), the incentives reduced the net annual health care costs, in Canadian dollars, for patients with hypertension (by approximately Can$308 per patient), chronic obstructive pulmonary disease (by Can$496), and congestive heart failure (by Can$96), but not diabetes (incentives cost about Can$148 more per patient). The incentives were also associated with fewer hospital days, fewer admissions and readmissions, and shorter lengths of hospital stays for all 4 groups. CONCLUSION: Although the available literature on pay for performance shows mixed results, we showed that the funding model used in British Columbia using incentive payments for primary care might reduce health care costs and hospital utilization. PMID- 26263391 TI - 120 Years of U.S. Residential Housing Stock and Floor Space. AB - Residential buildings are a key driver of energy consumption and also impact transportation and land-use. Energy consumption in the residential sector accounts for one-fifth of total U.S. energy consumption and energy-related CO2 emissions, with floor space a major driver of building energy demands. In this work a consistent, vintage-disaggregated, annual long-term series of U.S. housing stock and residential floor space for 1891-2010 is presented. An attempt was made to minimize the effects of the incompleteness and inconsistencies present in the national housing survey data. Over the 1891-2010 period, floor space increased almost tenfold, from approximately 24,700 to 235,150 million square feet, corresponding to a doubling of floor space per capita from approximately 400 to 800 square feet. While population increased five times over the period, a 50% decrease in household size contributed towards a tenfold increase in the number of housing units and floor space, while average floor space per unit remains surprisingly constant, as a result of housing retirement dynamics. In the last 30 years, however, these trends appear to be changing, as household size shows signs of leveling off, or even increasing again, while average floor space per unit has been increasing. GDP and total floor space show a remarkably constant growth trend over the period and total residential sector primary energy consumption and floor space show a similar growth trend over the last 60 years, decoupling only within the last decade. PMID- 26263392 TI - Identification of key neoculin residues responsible for the binding and activation of the sweet taste receptor. AB - Neoculin (NCL) is a heterodimeric protein isolated from the edible fruit of Curculigo latifolia. It exerts a taste-modifying activity by converting sourness to sweetness. We previously demonstrated that NCL changes its action on the human sweet receptor hT1R2-hT1R3 from antagonism to agonism as the pH changes from neutral to acidic values, and that the histidine residues of NCL molecule play critical roles in this pH-dependent functional change. Here, we comprehensively screened key amino acid residues of NCL using nuclear magnetic resonance (NMR) spectroscopy and alanine scanning mutagenesis. We found that the mutations of Arg48, Tyr65, Val72 and Phe94 of NCL basic subunit increased or decreased both the antagonist and agonist activities. The mutations had only a slight effect on the pH-dependent functional change. These residues should determine the affinity of NCL for the receptor regardless of pH. Their locations were separated from the histidine residues responsible for the pH-dependent functional change in the tertiary structure. From these results, we concluded that NCL interacts with hT1R2-hT1R3 through a pH-independent affinity interface including the four residues and a pH-dependent activation interface including the histidine residues. Thus, the receptor activation is induced by local structural changes in the pH-dependent interface. PMID- 26263390 TI - Neuronal MHC Class I Expression Is Regulated by Activity Driven Calcium Signaling. AB - MHC class I (MHC-I) molecules are important components of the immune system. Recently MHC-I have been reported to also play important roles in brain development and synaptic plasticity. In this study, we examine the molecular mechanism(s) underlying activity-dependent MHC-I expression using hippocampal neurons. Here we report that neuronal expression level of MHC-I is dynamically regulated during hippocampal development after birth in vivo. Kainic acid (KA) treatment significantly increases the expression of MHC-I in cultured hippocampal neurons in vitro, suggesting that MHC-I expression is regulated by neuronal activity. In addition, KA stimulation decreased the expression of pre- and post synaptic proteins. This down-regulation is prevented by addition of an MHC-I antibody to KA treated neurons. Further studies demonstrate that calcium dependent protein kinase C (PKC) is important in relaying KA simulation activation signals to up-regulated MHC-I expression. This signaling cascade relies on activation of the MAPK pathway, which leads to increased phosphorylation of CREB and NF-kappaB p65 while also enhancing the expression of IRF-1. Together, these results suggest that expression of MHC-I in hippocampal neurons is driven by Ca2+ regulated activation of the MAPK signaling transduction cascade. PMID- 26263393 TI - Gold Nanoparticle Internal Structure and Symmetry Probed by Unified Small-Angle X ray Scattering and X-ray Diffraction Coupled with Molecular Dynamics Analysis. AB - Shape and size are known to determine a nanoparticle's properties. Hardly ever studied in synthesis, the internal crystal structure (i.e., particle defects, crystallinity, and symmetry) is just as critical as shape and size since it directly impacts catalytic efficiency, plasmon resonance, and orients anisotropic growth of metallic nanoparticles. Hence, its control cannot be ignored any longer in today's research and applications in nanotechnology. This study implemented an unprecedented reliable measurement combining these three structural aspects. The unified small-angle X-ray scattering and diffraction measurement (SAXS/XRD) was coupled with molecular dynamics to allow simultaneous determination of nanoparticles' shape, size, and crystallinity at the atomic scale. Symmetry distribution (icosahedra-Ih, decahedra-Dh, and truncated octahedra-TOh) of 2-6 nm colloidal gold nanoparticles synthesized in organic solvents was quantified. Nanoparticle number density showed the predominance of Ih, followed by Dh, and little, if any, TOh. This result contradicts some theoretical predictions and highlights the strong effect of the synthesis environment on structure stability. We foresee that this unified SAXS/XRD analysis, yielding both statistical and quantitative counts of nanoparticles' symmetry distribution, will provide new insights into nanoparticle formation, growth, and assembly. PMID- 26263394 TI - Prevalence of HIV, Hepatitis B and C Infections and an Assessment of HCV Genotypes and Two IL28B SNPs among People Who Inject Drugs in Three Regions of Nepal. AB - As part of a comprehensive health care programme for people who use drugs in Nepal, HIV and viral hepatitis B and C status--including risk factors, HCV genotypes and co-infections--as well as two IL28B Single-nucleotide polymorphisms (SNPs) were assessed for a random sample of 401 people who inject drugs in three regions of Nepal: mid-western Terrai (Nepalgunj), the eastern region (Dharan, Biratnagar) and the central region (Kathmandu, Lalitpur and Chitwan). Individuals were included who showed at least a minimum of health care seeking behaviour. This latter criterion was defined by being registered with any organisation offering health services. The average age of the participants was 30.5 yrs, and the average length of intravenous drug use was 8.5 yrs. The prevalence rates of HBsAg, anti-HIV antibodies and HCV-RNA were 3.5%, 13.8% and 41.9%, respectively. Spontaneous HCV clearance was evident in 16% of all of those who tested positive for anti-HCV antibodies. Independent risk factors for HCV-RNA positivity were age, gender, geographical region, duration of injecting drug use, history of imprisonment and HIV co-infection. In the age group <=24 yrs, the rate of spontaneous HCV clearance was 43.5%. Overall, 59.8% of HCV infections were caused by HCV genotype 3 and 40.2% by HCV genotype 1. No other HCV genotypes were identified in this study. The IL28B SNP rs12979860 and rs8099917 were identified in 122 patients, and 75.4% of all participants had both favourable genotypes rs12979860 C/C and rs8099917 T/T. PMID- 26263396 TI - Structure-Activity Relationship Study of Hydroxycoumarins and Mushroom Tyrosinase. AB - The structure-activity relationships of four hydroxycoumarins, two with the hydroxyl group on the aromatic ring of the molecule and two with the hydroxyl group replacing hydrogen of the pyrone ring, and their interactions with mushroom tyrosinase were studied. These compounds displayed different behaviors upon action of the enzyme. The two compounds, ar-hydroxylated 6-hydroxycoumarin and 7 hydroxycoumarin, were both weak substrates of the enzyme. Interestingly, in both cases, the product of the catalysis was the 6,7-hydroxycoumarin, although 5,6- and 7,8-isomers could also theoretically be formed. Additionally, both were able to reduce the formation of dopachrome when tyrosinase acted on its typical substrate, L-tyrosine. Although none of the compounds that contained a hydroxyl group on the pyrone ring were substrates of tyrosinase, the 3-hydroxycoumarin was a potent inhibitor of the enzyme, and the 4-hydroxycoumarin was not an inhibitor. These results were compared with those obtained by in silico molecular docking predictions to obtain potentially useful information for the synthesis of new coumarin-based inhibitors that resemble the structure of the 3-hydroxycoumarin. PMID- 26263397 TI - Structure-Activity Relationship Study on Isothiocyanates: Comparison of TRPA1 Activating Ability between Allyl Isothiocyanate and Specific Flavor Components of Wasabi, Horseradish, and White Mustard. AB - Allyl isothiocyanate (ITC) (4) is the main pungent component in wasabi, and it generates an acrid sensation by activating TRPA1. The flavor and pungency of ITCs vary depending on the compound. However, the differences in activity to activate TRPA1 between ITCs are not known except for a few compounds. To investigate the effect of carbon chain length and substituents of ITCs, the TRPA1-activiting ability of 16 ITCs was measured. Since most of the ITCs showed nearly equal TRPA1 activiting potency, the ITC moiety is likely the predominant contributor to their TRPA1-activating abilities, and contributions of other functional groups to their activities to activate TRPA1 are comparatively small. PMID- 26263398 TI - [In Process Citation]. AB - The accelerated aging of the Canadian population is a recognized fact and leads to an increasing number of seniors with cognitive impairments (Curateur public du Quebec, 2010a). This has a definite impact on health professionals who have to assess their competency to live independently and manage their finances. This decision, which has important consequences for the person, must be based on an objective and rigorous assessment. The purpose of this paper is to analyse the available tools, both in the scientific literature and in clinical settings, to better document the various components to assess seniors' competency to live independently and manage their finances. The goal is to help practitioners who work with older people with cognitive impairments to accurately assess their ability to manage themselves and their property. A review of the relevant literature and training available, as well as three group consultations, showed that there is no consensus about the tools used to assess the capacity to take care of oneself and one's property. Additional studies are thus needed to fill the gap in knowledge about specific tools used to assess competency. PMID- 26263395 TI - Activation of matrix metalloproteinase in dorsal hippocampus drives improvement in spatial working memory after intra-VTA nicotine infusion in rats. AB - The hippocampus receives dopaminergic projections from the ventral tegmental area (VTA) and substantia nigra. These inputs appear to provide a modulatory signal that influences hippocampus-dependent behaviors. Enhancements in working memory performance have been previously reported following acute smoking/nicotine exposure. However, the underlying mechanism remains unclear. This study investigated the effects of nicotine on spatial working memory (SWM) and the mechanisms involved. Delayed alternation T-maze task was used to assess SWM. In situ and gel gelatin zymography were used to detect matrix metalloproteinase-9 (MMP-9) in SWM. Systemic or local (intra-VTA) administration of nicotine significantly improves SWM, which was accompanied by increased MMP-9 activity in dorsal hippocampus (dHPC). Intra-dHPC administration of MMP inhibitor FN-439 abolished the memory enhancement induced by intra-VTA nicotine infusion. FN-439 had no effect on locomotor behavior. Our data suggest that intra-VTA nicotine infusion activates MMP-9 in dHPC to improve SWM in rats. PMID- 26263399 TI - Relationships between the Active Aging Index and Disability-Free Life Expectancy: A Case Study in the Rajshahi District of Bangladesh. AB - Life expectancy has increased considerably throughout the world. In Bangladesh, life expectancy has increased from about 53 years in 1975 to 69 years in 2010. However, it is unknown whether the increase in life expectancy is simultaneously accompanied by an increase in disability-free life expectancy (DFLE). The purpose of the study described in this article was to explore the relationship between life expectancy and DFLE in the Rajshahi District of Bangladesh by examining the relationships between the Active Aging Index (AAI) and DFLE. The study fi ndings suggest that urban, more-educated, elderly males are more active in all aspects of life and have longer DFLE. Females are found to outlive males but are more likely to live a greater part of their remaining life with disability. Positive correlations between the AAI and DFLE suggest that older adults could enjoy more DFLE by involving themselves in active aging activities. PMID- 26263400 TI - Redox Potentials of Colloidal n-Type ZnO Nanocrystals: Effects of Confinement, Electron Density, and Fermi-Level Pinning by Aldehyde Hydrogenation. AB - Electronically doped colloidal semiconductor nanocrystals offer valuable opportunities to probe the new physical and chemical properties imparted by their excess charge carriers. Photodoping is a powerful approach to introducing and controlling free carrier densities within free-standing colloidal semiconductor nanocrystals. Photoreduced (n-type) colloidal ZnO nanocrystals possessing delocalized conduction-band (CB) electrons can be formed by photochemical oxidation of EtOH. Previous studies of this chemistry have demonstrated photochemical electron accumulation, in some cases reaching as many as >100 electrons per ZnO nanocrystal, but in every case examined to date this chemistry maximizes at a well-defined average electron density of ?Nmax? ~ (1.4 +/- 0.4) * 10(20) cm(-3). The origins of this maximum have never been identified. Here, we use a solvated redox indicator for in situ determination of reduced ZnO nanocrystal redox potentials. The Fermi levels of various photodoped ZnO nanocrystals possessing on average just one excess CB electron show quantum confinement effects, as expected, but are >600 meV lower than those of the same ZnO nanocrystals reduced chemically using Cp*2Co, reflecting important differences between their charge-compensating cations. Upon photochemical electron accumulation, the Fermi levels become independent of nanocrystal volume at ?N? above ~2 * 10(19) cm(-3), and maximize at ?Nmax? ~ (1.6 +/- 0.3) * 10(20) cm(-3). This maximum is proposed to arise from Fermi-level pinning by the two electron/two-proton hydrogenation of acetaldehyde, which reverses the EtOH photooxidation reaction. PMID- 26263401 TI - Security Analysis and Improvement of 'a More Secure Anonymous User Authentication Scheme for the Integrated EPR Information System'. AB - Over the past few years, secure and privacy-preserving user authentication scheme has become an integral part of the applications of the healthcare systems. Recently, Wen has designed an improved user authentication system over the Lee et al.'s scheme for integrated electronic patient record (EPR) information system, which has been analyzed in this study. We have found that Wen's scheme still has the following inefficiencies: (1) the correctness of identity and password are not verified during the login and password change phases; (2) it is vulnerable to impersonation attack and privileged-insider attack; (3) it is designed without the revocation of lost/stolen smart card; (4) the explicit key confirmation and the no key control properties are absent, and (5) user cannot update his/her password without the help of server and secure channel. Then we aimed to propose an enhanced two-factor user authentication system based on the intractable assumption of the quadratic residue problem (QRP) in the multiplicative group. Our scheme bears more securities and functionalities than other schemes found in the literature. PMID- 26263402 TI - Spectroscopy and computational studies on the interaction of octyl, dodecyl, and hexadecyl derivatives of anionic and cationic surfactants with adenosine deaminase. AB - Effects of sodium (octyl, dodecyl, hexadecyl) sulfate and their cationic analogous on the structure of adenosine deaminase (ADA) were investigated by fluorescence and circular dichroism spectroscopy as well as molecular dynamics simulation and docking calculation. Root-mean-square derivations, radius of gyration, solvent accessible surface area, and radial distribution function were obtained. The results showed that anionic and cationic surfactants reduce protein stability. Cationic surfactants have more effect on the ADA structure in comparison with anionic surfactants. More concentration and longer surfactants are parallel to higher denaturation. Furthermore, aggregation in the presence of anionic surfactants is more than cationic surfactants. Docking data showed that longer surfactants have more interaction energy and smaller ones bound to the active site. PMID- 26263403 TI - Antiretroviral activity and safety of once-daily etravirine in treatment-naive HIV-infected adults: 48-week results. AB - BACKGROUND: Etravirine (ETR), a non-nucleoside reverse transcriptase inhibitor approved for 200 mg twice-daily dosing in conjunction with other antiretrovirals (ARVs), has pharmacokinetic properties which support once-daily dosing. METHODS: In this single-arm, open-label study, 79 treatment-naive HIV-infected adults were assigned to receive ETR 400 mg plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) 300/200 mg once daily to assess antiviral activity, safety and tolerability. ARV activity at 48 weeks was determined by proportion of subjects with HIV-1 RNA<50 copies/ml (intention-to-treat, missing = failure). RESULTS: Of 79 eligible subjects, 90% were men, 62% African-American and 29% Caucasian. At baseline, median (Q1, Q3) age was 29 years (23, 44) and HIV-1 RNA 4.52 log10 copies/ml (4.07, 5.04). A total of 69 (87%) completed a week 48 visit and 61 (77%, 95% CI 66%, 86%) achieved HIV-1 RNA<50 copies/ml at week 48. At time of virological failure, genotypic resistance-associated mutations were detected in three participants, two with E138K (one alone and one with additional mutations). Median (95% CI) CD4(+) cell count increase was 163 (136, 203) cells/ul. Fifteen (19.0%) participants reported a new sign/symptom or lab abnormality >= Grade 3 and three participants (3.8%) permanently discontinued ETR due to toxicity. Two participants had psychiatric symptoms of any grade. There were no deaths. CONCLUSIONS: In this study of ARV-naive HIV-positive adults, once-daily ETR with TDF/FTC had acceptable antiviral activity and was well-tolerated. Once-daily ETR may be a plausible option as part of a combination ARV regimen for treatment naive individuals. ClinicalTrials.gov NCT00959894. PMID- 26263405 TI - Sensory processing in children with Autism Spectrum Disorder: Relationship with non-verbal IQ, autism severity and Attention Deficit/Hyperactivity Disorder symptomatology. AB - The main objective of this study was to analyze in a sample of children with ASD the relationship between sensory processing, social participation and praxis impairments and some of the child's characteristics, such as non-verbal IQ, severity of ASD symptoms and the number of ADHD symptoms (inattention and hyperactivity/impulsivity), both in the home and main-classroom environments. Participants were the parents and teachers of 41 children with ASD from 5 to 8 years old (M=6.09). They completed the Sensory Processing Measure (SPM) to evaluate sensory processing, social participation and praxis; the Gilliam Autism Rating Scale (GARS-2) to evaluate autism severity; and a set of items (the DSM-IV TR criteria) to evaluate the number of inattention and hyperactivity/impulsivity symptoms in the child. Non-verbal IQ - measured by the Raven's Coloured Progressive Matrices Test - did not show a relationship with any of the SPM variables. The SPM variables were significant predictors of autism severity and had similar weights in the two environments. In the case of ADHD symptoms, the SPM variables had a greater weight in the home than in the classroom environment, and they were significant predictors of both inattention and hyperactivity/impulsivity - especially inattention - only in the family context. The moderate association between inattention and auditory processing found in the main-classroom suggests the possible utility of certain measures aimed to simplify any classroom's acoustic environment. PMID- 26263406 TI - Exploring different explanations for performance on a theory of mind task in Williams syndrome and autism using eye movements. AB - The current study explored the looking behaviours of young children with Autism Spectrum Disorders (ASD), Williams syndrome (WS), and typically developing (TD) children while they were administered a low-verbal Theory of Mind (ToM) task. Although ToM performance in both clinical groups was impaired, only participants with WS showed small differences in looking behaviour at the start of the video. Furthermore, while TD children who passed the ToM task looked longer at the original hiding place there was no such contrast in the clinical groups. This shows that looking behaviour in ASD and WS is not necessarily atypical when saliency aspects such as language, background, and colour are removed and that differences in looking behaviour cannot explain ToM performance. PMID- 26263404 TI - Relationship between characteristics on magnetic resonance imaging and motor outcomes in children with cerebral palsy and white matter injury. AB - In a population cohort of children with white matter injury (WMI) and cerebral palsy (CP), we aimed to describe the magnetic resonance imaging (MRI) characteristics, identify key structure-function relationships, and classify the severity of WMI in a clinically relevant way. Stratified on MRI laterality/symmetry, variables indicating the extent and location of cerebral abnormalities for 272 children with CP and WMI on chronic-phase MRI were related to gross motor function and motor topography using univariable and multivariable approaches. We found that symmetrical involvement, severe WM loss in the hemispheres and corpus callosum, and cerebellar involvement were the strongest predictors of poor gross motor function, but the final model explained only a small proportion of the variability. Bilateral, extensive WM loss was more likely to result in quadriplegia, whereas volume loss in the posterior-mid WM more frequently resulted in diplegia. The extent and location of MRI abnormalities differed according to laterality/symmetry; asymmetry was associated with less extensive hemispheric involvement than symmetrical WMI, and unilateral lesions were more focal and located more anteriorly. In summary, laterality/symmetry of WMI, possibly reflecting different pathogenic mechanisms, together with extent of WM loss and cerebellar abnormality predicted gross motor function in CP, but to a limited extent. PMID- 26263407 TI - Assessment of physical fitness and exercise tolerance in children with developmental coordination disorder. AB - Children with developmental coordination disorder (DCD) have been shown to be less physically fit when compared to their typically developing peers. The purpose of the present study was to examine the relationships among body composition, physical fitness and exercise tolerance in children with and without DCD. Thirty-seven children between the ages of 7 and 9 years participated in this study. Participants were classified according to results obtained on the Movement Assessment Battery for Children (MABC) and were divided in 2 groups: 19 children with DCD and 18 children without DCD. All children performed the following physical fitness tests: The five-jump test (5JT), the triple-hop distance (THD) and the modified agility test (MAT). Walking distance was assessed using the 6 min walking test (6MWT). Children with DCD showed higher scores than children without DCD in all MABC subscale scores, as well as in the total score (p<0.001). Participants with DCD were found to perform significantly worse on the MAT (p<0.001), the THD (p<0.001) and 5JT (p<0.05). Moreover, children with DCD had poorer performance on the 6MWT than children without DCD (p<0.01). Our results found significant correlations among body mass index (BMI), THD (r=0.553, p<0.05), 5JT (r=0.480, p<0.05) and 6MWT (r=0.544, p<0.05) only in DCD group. A significant correlation between MAT and 5JT (r=-0.493, p<0.05) was found. Similarly, THD and 5JT (r=0.611, p<0.01) was found to be correlated in children with DCD. We also found relationships among 6MWT and MAT (r=-0.522, p<0.05) and the 6MWT and 5JT (r=0.472, p<0.05) in DCD group. In addition, we found gender specific patterns in the relationship between exercise tolerance, explosive strength, power, DCD, and BMI. In conclusion, the present study revealed that BMI was indicative of poorer explosive strength, power and exercise tolerance in children with DCD compared to children without DCD probably due to a limited coordination on motor control. PMID- 26263408 TI - Measuring public discomfort at meeting people with disabilities. AB - The discomfort reported by the general public at the prospect of personal contact with marginalised groups is an expression of the stigma they experience. This has been widely studied in relation to ethnic minorities and immigrants but less so for persons with disabilities. A national survey with a representative sample of over 1100 Irish adults provided an opportunity to examine reported discomfort with persons who had different impairments, including mental health conditions, with four other minority groups. Moreover, the personal and situational variables associated with expressions of discomfort were identified. Respondents were most comfortable having persons with physical and sensorial disabilities living in their neighbourhood or in their workplace but less so for persons with intellectual disabilities and even less for people with mental health conditions. They were much less comfortable with the four other social groups: gay, lesbian or bisexual people; Eastern European migrant workers; black and ethnic minority groups and least of all, travellers. Moreover, a factor analysis confirmed that the scores given to the impaired groups were significantly correlated with each other but less so with the other four social groupings, although these were significantly inter-correlated among themselves. Respondents who were more comfortable with both sets of minority groups tended to have more social connections in their personal lives and to reside in towns or villages rather than cities. They also expressed more positive attitudes to the inclusion of persons with disabilities in Irish society. The gradient in levels of public discomfort across minority groups may provide a sensitive indicator of the differential stigma experienced by persons with impairments within societies but there remains the possibility that an alliance with other minority groups would also help to promote more positive attitudes and reduce their wider social exclusion. PMID- 26263409 TI - Reduced motor imagery efficiency is associated with online control difficulties in children with probable developmental coordination disorder. AB - Recent evidence indicates that the ability to correct reaching movements in response to unexpected target changes (i.e., online control) is reduced in children with developmental coordination disorder (DCD). Recent computational modeling of human reaching suggests that these inefficiencies may result from difficulties generating and/or monitoring internal representations of movement. This study was the first to test this putative relationship empirically. We did so by investigating the degree to which the capacity to correct reaching mid flight could be predicted by motor imagery (MI) proficiency in a sample of children with probable DCD (pDCD). Thirty-four children aged 8 to 12 years (17 children with pDCD and 17 age-matched controls) completed the hand rotation task, a well-validated measure of MI, and a double-step reaching task (DSRT), a protocol commonly adopted to infer one's capacity for correcting reaching online. As per previous research, children with pDCD demonstrated inefficiencies in their ability to generate internal action representations and correct their reaching online, demonstrated by inefficient hand rotation performance and slower correction to the reach trajectory following unexpected target perturbation during the DSRT compared to age-matched controls. Critically, hierarchical moderating regression demonstrated that even after general reaching ability was controlled for, MI efficiency was a significant predictor of reaching correction efficiency, a relationship that was constant across groups. Ours is the first study to provide direct pilot evidence in support of the view that a decreased capacity for online control of reaching typical of DCD may be associated with inefficiencies generating and/or using internal representations of action. PMID- 26263410 TI - Does the Cerebrospinal Fluid Reflect Altered Redox State But Not Neurotrophic Support Loss in Parkinson's Disease? AB - Alteration in neurotrophic factors support and antioxidant defenses in the central nervous system (CNS) along with deficit of ferritin have been associated with idiopathic Parkinson's disease (PD). The objectives were to analyze in the cerebrospinal fluid (CSF) of patients with PD and controls the following: (i) the levels of the neuroprotectant factors glial cell line-derived neurotrophic factor, persephin, neurturin, and brain-derived neurotrophic factor, (ii) the levels of transforming growth factor-beta1 (TGFbeta1) and transforming growth factor-beta2 (TGFbeta2), proinflammatory factors, (iii) the activity of the antioxidant enzymes glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), catalase, superoxide dismutases (SODs), and peroxiredoxins (PRDxs), and (iv) ferritin levels. The study revealed that, among neurotrophic factors, only TGFbeta1 levels were found to be enhanced in patients with PD (early, p < 0.05; advanced, p < 0.02). Regarding antioxidant enzymes, the activity of GPx, catalase, and PRDxs, all hydrogen peroxide scavengers, was found to be significantly reduced in patients (GPx, p < 0.001; catalase, p < 0.01; PRDxs, p < 0.01, one-way analysis of variance). Finally, ferritin content in CSF was significantly diminished over time in patients (early, p < 0.01, -49%; advanced, p < 0.001, -80.7%). Our observations lead to the hypothesis that parkinsonian patients suffer from a serious disturbance of redox state in the CNS, as evaluated through the CSF, characterized by reduced hydrogen peroxide scavenging and iron storage. PMID- 26263411 TI - Family ties: young breast cancer patients and their children. AB - BACKGROUND: This study assessed the interaction of "family ties" in a cohort of young breast cancer patients. METHODS: Based on the Basel Breast Cancer Database, we analysed an unselected, consecutive cohort of patients who were <=40 years at breast cancer diagnosis (n = 100). RESULTS: Sixty patients had children at the time of diagnosis (mean number of children: 1.03). Only four patients had desired children after BC therapy. The average age of the children at breast cancer diagnosis of their mother was 7.7 years. The mean age of the children whose mothers died of breast cancer at the time of their mother's death was 13.1 years; these children (n = 37) lived an average of 84.7 months with the illness of their mother. Parity status was not a significant factor for compliance/persistence to adjuvant chemotherapy (p = 1.00). Patients who had children were more likely to be compliant/persistent to endocrine therapy (p = 0.021). Out of these patients, 41.2% rejected or discontinued endocrine therapy with the explicit intention to get pregnant. CONCLUSIONS: Desire for children was an important factor in refusing endocrine therapy. This clearly highlights the enormous pressure that many young women face in this situation. About a third of the children whose mothers were diagnosed with breast cancer experienced the palliative situation and the death of their mother. Since many of these children are confronted with a cancerous disease of their mothers during half of their childhood, special attention should be paid to age-appropriate support of a child in all phases of the mother's disease. PMID- 26263413 TI - Characterizing breast lesions through robust multimodal data fusion using independent diffuse optical and x-ray breast imaging. AB - To enable tissue function-based tumor diagnosis over the large number of existing digital mammography systems worldwide, we propose a cost-effective and robust approach to incorporate tomographic optical tissue characterization with separately acquired digital mammograms. Using a flexible contour-based registration algorithm, we were able to incorporate an independently measured two dimensional x-ray mammogram as structural priors in a joint optical/x-ray image reconstruction, resulting in improved spatial details in the optical images and robust optical property estimation. We validated this approach with a retrospective clinical study of 67 patients, including 30 malignant and 37 benign cases, and demonstrated that the proposed approach can help to distinguish malignant from solid benign lesions and fibroglandular tissues, with a performance comparable to the approach using spatially coregistered optical/x-ray measurements. PMID- 26263414 TI - Use of optical skin phantoms for preclinical evaluation of laser efficiency for skin lesion therapy. AB - Skin lesions are commonly treated using laser heating. However, the introduction of new devices into clinical practice requires evaluation of their performance. This study presents the application of optical phantoms for assessment of a newly developed 975-nm pulsed diode laser system for dermatological purposes. Such phantoms closely mimic the absorption and scattering of real human skin (although not precisely in relation to thermal conductivity and capacitance); thus, they can be used as substitutes for human skin for approximate evaluation of laser heating efficiency in an almost real environment. Thermographic imaging was applied to measure the spatial and temporal temperature distributions on the surface of laser-irradiated phantoms. The study yielded results of heating with regard to phantom thickness and absorption, as well as laser settings. The methodology developed can be used in practice for preclinical evaluations of laser treatment for dermatology. PMID- 26263415 TI - Polarization dependence of aligned collagen tissues imaged with second harmonic generation microscopy. AB - A polarimetric second harmonic generation (SHG) microscope was used to analyze the dependence between polarization and SHG signal from collagen-based samples. A theoretical model was also developed to investigate the SHG intensity as a function of different polarization states for a set of quasiparallel fibers. Numerical simulations were compared to experimental SHG intensity values and a fairly good agreement was found. Linear polarized light produced periodical changes in the emitted SHG signal with a maximum of intensity corresponding to polarization parallel to the main orientation of the fibers, regardless the ratio of hyperpolarizabilities, rhorho . A similar behavior was found for elliptical states located along a vertical meridian on the Poincare sphere (i.e., null azimuth) although the modulation of the SHG signal was different. Our numerical calculations described a dramatic change in this regular trend when rhorho changed from positive to negative values. Moreover, we provide an experimental method (based on the analysis of the modulation of the SHG signal) to determine the value of the ratio rhorho and, consequently, to obtain information about the internal organization of the collagen fibers. PMID- 26263412 TI - Raman spectroscopy for label-free identification of calciphylaxis. AB - Calciphylaxis is a painful, debilitating, and premorbid condition, which presents as calcified vasculature and soft tissues. Traditional diagnosis of calciphylaxis lesions requires an invasive biopsy, which is destructive, time consuming, and often leads to exacerbation of the condition and infection. Furthermore, it is difficult to find small calcifications within a large wound bed. To address this need, a noninvasive diagnostic tool may help clinicians identify ectopic calcified mineral and determine the disease margin. We propose Raman spectroscopy as a rapid, point-of-care, noninvasive, and label-free technology to detect calciphylaxis mineral. Debrided calciphylactic tissue was collected from six patients and assessed by microcomputed tomography (micro-CT). Micro-CT confirmed extensive deposits in three specimens, which were subsequently examined with Raman spectroscopy. Raman spectra confirmed that deposits were consistent with carbonated apatite, consistent with the literature. Raman spectroscopy shows potential as a noninvasive technique to detect calciphylaxis in a clinical environment. PMID- 26263416 TI - Quantitative phase imaging with molecular sensitivity using photoacoustic microscopy with a miniature ring transducer. AB - We present a dual-modality system for both structural and molecular cell imaging based on coregistered quantitative phase imaging (QPI) and photoacoustic microscopy (PAM). The QPI system was based on off-axis holography, whereas the PAM system comprised a sinusoidally modulated optical source for excitation and a narrow-band low profile and low-cost ring ultrasonic transducer for detection. This approach facilitated a simple confocal alignment of the excitation beams of both modalities and the ultrasonic detector. This system was demonstrated by imaging endogenous molecules in red blood cells (RBCs) as well as by imaging exogenous molecular labels on cancer cells using gold nanoparticles (GNPs) functionalized to target epidermal growth factor receptor. QPI provided high resolution imaging of the cellular structures while PAM provided molecular contrast. This dual-modality microscopy method can potentially be implemented as a compact and low cost cellular diagnostic assay. PMID- 26263417 TI - Performance characteristics of an interventional multispectral photoacoustic imaging system for guiding minimally invasive procedures. AB - Precise device guidance is important for interventional procedures in many different clinical fields including fetal medicine, regional anesthesia, interventional pain management, and interventional oncology. While ultrasound is widely used in clinical practice for real-time guidance, the image contrast that it provides can be insufficient for visualizing tissue structures such as blood vessels, nerves, and tumors. This study was centered on the development of a photoacoustic imaging system for interventional procedures that delivered excitation light in the ranges of 750 to 900 nm and 1150 to 1300 nm, with an optical fiber positioned in a needle cannula. Coregistered B-mode ultrasound images were obtained. The system, which was based on a commercial ultrasound imaging scanner, has an axial resolution in the vicinity of 100 MUm and a submillimeter, depth-dependent lateral resolution. Using a tissue phantom and 800 nm excitation light, a simulated blood vessel could be visualized at a maximum distance of 15 mm from the needle tip. Spectroscopic contrast for hemoglobin and lipids was observed with ex vivo tissue samples, with photoacoustic signal maxima consistent with the respective optical absorption spectra. The potential for further optimization of the system is discussed. PMID- 26263418 TI - Toddlers with Early Behavioral Problems at Higher Family Demographic Risk Benefit the Most from Maternal Emotion Talk. AB - OBJECTIVE: To test the hypothesis that toddlers at highest risk for behavioral problems from the most economically vulnerable families will benefit most from maternal talk about emotions. METHODS: This study included 89 toddlers and mothers from low-income families. Behavioral problems were rated at 2 time points by masters-level trained Early Head Start home visiting specialists. Maternal emotion talk was coded from a wordless book-sharing task. Coding focused on mothers' emotion bridging, which included labeling emotions, explaining the context of emotions, noting the behavioral cues of emotions, and linking emotions to toddlers' own experiences. Maternal demographic risk reflected a composite score of 5 risk factors. RESULTS: A significant 3-way interaction between Time 1 toddler behavior problems, maternal emotion talk, and maternal demographic risk (p = .001) and examination of slope difference tests revealed that when maternal demographic risk was greater, more maternal emotion talk buffered associations between earlier and later behavior problems. Greater demographic risk and lower maternal emotion talk intensified Time 1 behavior problems as a predictor of Time 2 behavior problems. The model explained 54% of the variance in toddlers' Time 2 behavior problems. Analyses controlled for maternal warmth to better examine the unique contributions of emotion bridging to toddlers' behaviors. CONCLUSION: Toddlers at highest risk, those with more early behavioral problems from higher demographic-risk families, benefit the most from mothers' emotion talk. Informing parents about the use of emotion talk may be a cost-effective, simple strategy to support at-risk toddlers' social-emotional development and reduce behavioral problems. PMID- 26263419 TI - 8p23.1 Interstitial Deletion in a Patient with Congenital Cardiopathy, Neurobehavioral Disorders, and Minor Signs Suggesting 22q11.2 Deletion Syndrome. AB - Copy number variation studies of known disorders have the potential to improve the characterization of clinical phenotypes and may help identifying candidate genes and their pathways. The authors described a child with congenital heart disease, microcephaly, facial dysmorphisms, developmental delay, learning difficulties, and behavioral problems. There was initially a clinical suspicion of 22q11.2 deletion syndrome (22q11.2 DS), but molecular cytogenetic analysis (array genomic hybridization [aGH]) showed the presence of a de novo 3.6-Mb interstitial microdeletion in 8p23.1. The main features of 8p23.1 DS include congenital heart disease and behavioral problems, in addition to minor dysmorphisms and mental delay. Therefore, this article highlights the application of aGH to investigate 8p23.1 deletion in nonconfirmed 22q11.2 DS patients presenting neurobehavioral disorders, congenital cardiopathy, and minor dysmorphisms. PMID- 26263420 TI - Culturally Appropriate Training for Remote Australian Aboriginal Health Workers: Evaluation of an Early Child Development Training Intervention. AB - OBJECTIVE: This study aimed to design, implement, and evaluate training in early childhood development (ECD) and in the use of a culturally adapted developmental screening tool, for remote Australian Aboriginal Health Workers (AHWs) and other remote health practitioners. METHOD: A case-study evaluation framework was adopted. Two remote Australian Aboriginal health services were selected as case study sites. Materials review, semistructured interviews, posttraining feedback surveys, and workplace observations contributed to the evaluation, guided by Guskey's 5-level education evaluation model. RESULTS: Remote health practitioners (including AHWs and Remote Area Nurses) and early childhood staff from the sites participated in a customized 21/2 day training workshop focusing on the principles of ECD and the use of the culturally adapted Ages and Stages Questionnaire, third edition. Consistent with adult learning theories and recommendations from the literature regarding culturally appropriate professional development methods in this context, the workshop comprised interactive classroom training, role-plays, and practice coaching in the workplace, including booster training. The qualitative findings demonstrated that mode of delivery was effective and valued by participants. The workshop improved practitioners' skills, knowledge, competence, and confidence to identify and manage developmental difficulties and promote child development, evidenced on self report and workplace clinical observation. CONCLUSION: The findings suggest that the practical, culturally appropriate training led to positive learning outcomes in developmental practice for AHWs and other remote health practitioners. This is an important finding that has implications in other Indigenous contexts, as effective training is a critical component of any practice improvement intervention. Further research examining factors influencing practice change is required. PMID- 26263421 TI - PNA-Rose Bengal Conjugates as Efficient DNA Photomodulators. AB - Selective photoinduced modulation of DNA may provide a powerful therapeutic tool allowing spatial and temporal control of the photochemical reaction. We have explored the photoreactivity of peptide nucleic acid (PNA) conjugates that were conjugated to a highly potent photosensitizer, Rose Bengal (RB). In addition, a short PEGylated peptide (K-PEG8-K) was conjugated to the C-terminus of the PNA to improve its water solubility. A short irradiation (visible light) of PNA conjugates with a synthetic DNA resulted in highly efficient photomodulation of the DNA as evidenced by polyacrylamide gel electrophoresis (PAGE). In addition, a PNA-RB conjugate replacing K-PEG8-K with four l-glutamic acids (E4) was found to be photoinactive. Irradiation of active PNA-RB conjugates with synthetic DNA in D20 augments the photoactivity; supporting the involvement of singlet oxygen. PAGE, HPLC, and MALDI-TOF analyses indicate that PNA-DNA photo-cross-linking is a significant pathway in the observed photoreactivity. Selective photo-cross linking of such PNA-RB conjugates may be a novel approach to selective photodynamic therapy (sPDT) as such molecules would be sequence-specific, cell permeable, and photoactivated in the visible region. PMID- 26263422 TI - The Polypill: From Promise to Pragmatism. AB - Mark Huffman asks what happened to the polypill to reduce cardiovascular risk, explores the promise it still holds, and considers how best to turn promise into reality. PMID- 26263423 TI - Novel relationships between B12, folate and markers of inflammation, oxidative stress and NAD(H) levels, systemically and in the CNS of a healthy human cohort. AB - OBJECTIVE: To evaluate the relationship between folate, cobalamin (Cbl), and homocysteine (Hcy), and markers of inflammation and oxidative stress within the periphery and central nervous system (CNS) of a healthy human cohort. METHODS: Thirty-five matched cerebrospinal fluid (CSF) and plasma samples were collected from consenting participants who required a spinal tap for the administration of anaesthetic. Plasma concentrations of Hcy and both plasma and CSF levels of folate, Cbl, nicotinamide adenine dinucleotide (NAD(H)) and markers of inflammation (interleukin-6, IL-6), and oxidative stress (F2-isoprostanes, 8 hydroxy-2'-deoxyguanosine (8-OHdG), and total antioxidant capacity (TAC)) were quantified. RESULTS: In the peripheral circulation, positive associations were observed between plasma folate and Cbl, and plasma TAC (P <= 0.01; P <= 0.01) and plasma NAD(H) (P <= 0.05; P <= 0.05) levels, respectively. Plasma folate was inversely associated with plasma Hcy concentrations (P <= 0.05); however, no statistically significant relationships were observed between plasma Hcy and plasma markers of inflammation, oxidative stress, or [NAD(H)]. Within the CNS plasma Hcy correlated positively with CSF IL-6 (P <= 0.01) and negatively with CSF NAD(H) (P <= 0.05) concentrations. An inverse association was observed between CSF folate and CSF levels of IL-6 (P <= 0.05). Unexpectedly, a positive association between CSF Cbl and CSF 8-OHdG levels was also found (P <= 0.01). DISCUSSION: These results indicate that folate and Cbl concentrations may influence the levels of oxidative damage, inflammation, and NAD(H), both systemically and within the CNS. PMID- 26263424 TI - Data mining and education. AB - An emerging field of educational data mining (EDM) is building on and contributing to a wide variety of disciplines through analysis of data coming from various educational technologies. EDM researchers are addressing questions of cognition, metacognition, motivation, affect, language, social discourse, etc. using data from intelligent tutoring systems, massive open online courses, educational games and simulations, and discussion forums. The data include detailed action and timing logs of student interactions in user interfaces such as graded responses to questions or essays, steps in rich problem solving environments, games or simulations, discussion forum posts, or chat dialogs. They might also include external sensors such as eye tracking, facial expression, body movement, etc. We review how EDM has addressed the research questions that surround the psychology of learning with an emphasis on assessment, transfer of learning and model discovery, the role of affect, motivation and metacognition on learning, and analysis of language data and collaborative learning. For example, we discuss (1) how different statistical assessment methods were used in a data mining competition to improve prediction of student responses to intelligent tutor tasks, (2) how better cognitive models can be discovered from data and used to improve instruction, (3) how data-driven models of student affect can be used to focus discussion in a dialog-based tutoring system, and (4) how machine learning techniques applied to discussion data can be used to produce automated agents that support student learning as they collaborate in a chat room or a discussion board. PMID- 26263425 TI - Basic mathematical cognition. AB - Mathematics is a powerful tool for describing and developing our knowledge of the physical world. It informs our understanding of subjects as diverse as music, games, science, economics, communications protocols, and visual arts. Mathematical thinking has its roots in the adaptive behavior of living creatures: animals must employ judgments about quantities and magnitudes in the assessment of both threats (how many foes) and opportunities (how much food) in order to make effective decisions, and use geometric information in the environment for recognizing landmarks and navigating environments. Correspondingly, cognitive systems that are dedicated to the processing of distinctly mathematical information have developed. In particular, there is evidence that certain core systems for understanding different aspects of arithmetic as well as geometry are employed by humans and many other animals. They become active early in life and, particularly in the case of humans, develop through maturation. Although these core systems individually appear to be quite limited in application, in combination they allow for the recognition of mathematical properties and the formation of appropriate inferences based upon those properties. In this overview, the core systems, their roles, their limitations, and their interaction with external representations are discussed, as well as possibilities for how they can be employed together to allow us to reason about more complex mathematical domains. PMID- 26263426 TI - Intonational meaning. AB - Traditionally, prosodic studies have focused on the study of intonational form and the study of intonational meaning has been relatively neglected. Similarly, the fields of semantics and pragmatics have paid little attention to the pragmatic uses of intonation. As a result, there is no firm agreement within the linguistic community on how to integrate the analysis of intonational meaning across languages into a unified prosodic, semantic, and pragmatic approach. This article provides an overview of the literature on intonational meaning, describing the recent advances made in the fields of prosody, semantics/pragmatics, and syntax. Several theoretical approaches to explaining the semantics and pragmatics of intonation are presented. A common feature to most frameworks is that intonation (1) should be regarded as an integral part of linguistic grammar; and (2) typically encodes meanings related to the modal aspect of propositions. However, features such as compositionality, duality of structure, and context-dependency are still hotly debated issues. These features will be discussed from different theoretical perspectives, and we will identify potential advances related to the full integration of intonational meaning into dynamic and multidimensional models of meaning. PMID- 26263427 TI - Learning and cognition in insects. AB - Insects possess small brains but exhibit sophisticated behavioral performances. Recent works have reported the existence of unsuspected cognitive capabilities in various insect species, which go beyond the traditional studied framework of simple associative learning. In this study, I focus on capabilities such as attention, social learning, individual recognition, concept learning, and metacognition, and discuss their presence and mechanistic bases in insects. I analyze whether these behaviors can be explained on the basis of elemental associative learning or, on the contrary, require higher-order explanations. In doing this, I highlight experimental challenges and suggest future directions for investigating the neurobiology of higher-order learning in insects, with the goal of uncovering l architectures underlying cognitive processing. PMID- 26263428 TI - Cumulative risk and developmental health: an argument for the importance of a family-wide science. AB - A substantial body of research links social disadvantage and developmental health via a cascade running from poverty, to cumulative psychosocial risk, to disrupted family dynamics, to child biological regulatory systems and neurocognitive processing, and finally to morbidity across the lifespan. Most research in this area employs single-dyad or between-family methodology. While informative, there are limitations to this approach. Specifically, it is impossible to determine how risk alters psychosocial environments that are similar for all persons within a household, versus processes that are unique to particular children. This is important in light of literature citing the primacy of child-specific environments in driving developmental health. Methodologically speaking, there are both benefits and challenges to family-wide approaches that differentiate between- and within-family environments. This review describes literature linking cumulative risk and developmental health via family process, while articulating the importance of family-wide approaches. Areas of shortcoming and recommendations for a family-wide science are provided. PMID- 26263429 TI - Low Cerebral Oxygenation Levels during Resuscitation in Out-of-hospital Cardiac Arrest Are Associated with Hyperfibrinolysis. AB - BACKGROUND: The authors investigated whether patients with out-of-hospital cardiac arrest with an initial low cerebral oxygen level during cardiopulmonary resuscitation are more prone to develop hyperfibrinolysis than patients with normal cerebral oxygenation levels and which part of the fibrinolytic system is involved in this response. METHODS: In 46 patients, hyperfibrinolysis was diagnosed immediately upon emergency department admission using rotational thromboelastometry and defined as a lysis more than 15%. Simultaneously, initial cerebral tissue oxygenation was measured using near-infrared spectroscopy, and oxygen desaturation was defined as a tissue oxygenation index (TOI) of 50% or less. Blood sample analysis included markers for hypoperfusion and fibrinolysis. RESULTS: There was no difference in prehospital cardiopulmonary resuscitation duration between patients with or without hyperfibrinolysis. An initial TOI of 50% or less was associated with more clot lysis (91% [17 to 100%; n = 16]) compared with patients with a normal TOI (6% [4 to 11%]; n = 30; P < 0.001), with lower levels of plasminogen (151.6 +/- 61.0 vs. 225.3 +/- 47.0 MUg/ml; P < 0.001) and higher levels of tissue plasminogen activator (t-PA; 18.3 +/- 7.4 vs. 7.9 +/- 4.7 ng/ml; P < 0.001) and plasminogen activator inhibitor-1 (19.3 +/- 8.9 vs. 12.1 +/- 6.1 ng/ml; P = 0.013). There were no differences in (activated) protein C levels among groups. The initial TOI was negatively correlated with t-PA (r = 0.69; P < 0001). Mortality rates were highest in patients with hyperfibrinolysis. CONCLUSION: Activation of the fibrinolytic system is more common in out-of hospital cardiac arrest patients with an initial cerebral tissue oxygenation value of 50% or less during resuscitation and is linked to increased levels of t PA rather than involvement of protein C. PMID- 26263430 TI - Neuropathic Allodynia Involves Spinal Neurexin-1beta-dependent Neuroligin 1/Postsynaptic Density-95/NR2B Cascade in Rats. AB - BACKGROUND: Neuroligin-1 (NL1) forms a complex with the presynaptic neurexin 1beta (Nrx1b), regulating clustering of N-methyl-D-aspartate receptors with postsynaptic density-95 (PSD-95) to underlie learning-/memory-associated plasticity. Pain-related spinal neuroplasticity shares several common features with learning-/memory-associated plasticity. The authors thereby investigated the potential involvement of NL1-related mechanism in spinal nerve ligation (SNL) associated allodynia. METHODS: In 626 adult male Sprague-Dawley rats, the withdrawal threshold and NL1, PSD-95, phosphorylated NR2B (pNR2B) expressions, interactions, and locations in dorsal horn (L4 to L5) were compared between the sham operation and SNL groups. A recombinant Nrx1b Fc chimera (Nrx1b Fc, 10 MUg, 10 MUl, i.t., bolus), antisense small-interfering RNA targeting to NL1 (10 MUg, 10 MUl, i.t., daily for 4 days), or NR2B antagonist (Ro 25-6981; 1 MUM, 10 MUl, i.t., bolus) were administered to SNL animals to elucidate possible cascades involved. RESULTS: SNL-induced allodynia failed to affect NL1 or PSD-95 expression. However, pNR2B expression (mean +/- SD from 13.1 +/- 2.87 to 23.1 +/- 2.52, n = 6) and coexpression of NL1-PSD-95, pNR2B-PSD-95, and NL1-total NR2B were enhanced by SNL (from 10.7 +/- 2.27 to 22.2 +/- 3.94, 11.5 +/- 2.15 to 23.8 +/- 3.32, and 8.9 +/- 1.83 to 14.9 +/- 2.27 at day 7, n = 6). Furthermore, neuron localized pNR2B PSD-95-pNR2B double-labeled and NL1/PSD-95/pNR2B triple-labeled immunofluorescence in the ipsilateral dorsal horn was all prevented by Nrx1b Fc and NL1-targeted small-interfering RNA designed to block and prevent NL1 expression. Without affecting NL1-PSD-95 coupling, Ro 25-6981 decreased the SNL induced PSD-95-pNR2B coprecipitation (from 18.7 +/- 1.80 to 14.7 +/- 2.36 at day 7, n = 6). CONCLUSION: SNL-induced allodynia, which is mediated by the spinal NL1/PSD-95/pNR2B cascade, can be prevented by blockade of transsynaptic Nrx1b-NL1 interactions. PMID- 26263431 TI - Risk and Outcomes of Substance Use Disorder among Anesthesiology Residents: A Matched Cohort Analysis. AB - BACKGROUND: The goal of this work is to evaluate selected risk factors and outcomes for substance use disorder (SUD) in physicians enrolled in anesthesiology residencies approved by the Accreditation Council for Graduate Medical Education. METHODS: For each of 384 individuals with evidence of SUD while in primary residency training in anesthesiology from 1975 to 2009, two controls (n = 768) who did not develop SUD were identified and matched for sex, age, primary residency program, and program start date. Risk factors evaluated included location of medical school training (United States vs. other) and anesthesia knowledge as assessed by In-Training Examination performance. Outcomes (assessed to December 31, 2013, with a median follow-up time of 12.2 and 15.1 yr for cases and controls, respectively) included mortality and profession-related outcomes. RESULTS: Receiving medical education within the United States, but not performance on the first in-training examination, was associated with an increased risk of developing SUD as a resident. Cases demonstrated a marked increase in the risk of death after training (hazard ratio, 7.9; 95% CI, 3.1 to 20.5), adverse training outcomes including failure to complete residency (odds ratio, 14.9; 95% CI, 9.0 to 24.6) or become board certified (odds ratio, 10.4; 95% CI, 7.0 to 15.5), and adverse medical licensure actions subsequent to residency (hazard ratio, 6.8; 95% CI, 3.8 to 12.2). As of the end of follow-up, 54 cases (14.1%) were deceased compared with 10 controls (1.3%); 28 cases and no controls died during residency. CONCLUSION: The attributable risk of SUD to several adverse outcomes during and after residency training, including death and adverse medical license actions, is substantial. PMID- 26263432 TI - Serum macrophage migration inhibitory factor levels are associated with angiographically complex coronary lesions in patients with coronary artery disease. AB - BACKGROUND: Rupture of vulnerable plaque with subsequent thrombus formation has been implicated as the most common pathogenic mechanism responsible for acute coronary syndrome (ACS). Angiographic coronary lesion complexity has been reported to reflect plaque vulnerability. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine and might be involved in the pathophysiology of atherosclerotic plaque destabilization. OBJECTIVE: This study was designed to investigate if serum MIF levels are associated with angiographic coronary lesion complexity in patients with coronary artery disease (CAD). MATERIALS AND METHODS: A total of 232 consecutive CAD patients and 76 controls were recruited. CAD patients were subdivided according to the presence of ACS (n=138) or stable angina pectoris (SAP) (n=98). Coronary lesion morphology was assessed by coronary angiography. Serum MIF levels were measured by an enzyme-linked immunosorbent assay. RESULTS: SAP patients had significantly higher serum MIF levels compared with healthy controls, and ACS patients had significantly higher serum MIF levels compared with SAP patients. In SAP patients, serum MIF levels were independently associated with the presence of complex coronary lesion. In ACS patients, serum MIF levels increased in conjunction with the extent of complex lesions. CONCLUSIONS: Serum MIF levels are a potential biomarker for reflecting the presence and severity of angiographically complex coronary lesion in CAD patients. PMID- 26263433 TI - Trauma, Time, and Transfusions: A Longitudinal Analysis of Coagulation Markers in Severely Injured Trauma Patients Receiving Modified Whole Blood or Component Blood Products. AB - OBJECTIVE: The current study leveraged data from the Early Whole Blood (EWB) trial to explore the effects of modified whole blood (mWB) versus component (COMP) transfusions on coagulation parameters over time using longitudinal statistical methods. STUDY DESIGN AND METHODS: The EWB study was a single-center randomized controlled trial, approved by the local IRB. Adult patients at highest level trauma activations were randomized into mWB or COMP groups. Coagulation status was evaluated (at times 0, 3, 6, 12, and 24 h postadmission) using thrombelastography, platelet aggregometry, and calibrated automated thrombograms. Longitudinal statistical analyses with generalized estimating equations (GEE) were used to evaluate the effects of group, time, transfusion types, and their respective interactions on changes in measured coagulation markers. RESULTS: A total of 59 patients were enrolled and adhered to protocol in the EWB trial, 25 in the mWB group, and 34 in the COMP group. Patients in both the mWB and COMP groups demonstrated a significant decline in their thrombelastography parameters during the first 3-6 h, specifically K-time, alpha-angle, maximum amplitude, G, and LY30. Patients receiving mWB exhibited improved thrombin potential than those receiving COMP. Platelet count and function declined over time in both mWB and COMP groups; however, platelet aggregation in response to ristocetin in the mWB group was significantly improved at 12 h compared with the COMP group. The longitudinal GEE model revealed significant group-time interactive effects on the changes in coagulation markers and significant effect of platelet transfusions on improvements in coagulation profile. CONCLUSIONS: We observed significant interactive group-time effects, indicating that the types of transfusion as well as the time of transfusion significantly affect the patient's coagulation status. Our pilot data suggest that there is an improvement in platelet function with mWB, but further studies are needed. Regardless, platelet transfusions were associated with improvements in coagulation over time in both the groups. PMID- 26263435 TI - Increased Fluid Administration After Early Acute Kidney Injury is Associated with Less Renal Recovery. AB - INTRODUCTION: In acute kidney injury (AKI), fluid accumulation is associated with poor outcome. We aimed to determine whether fluid intake or output had the major role. METHODS: Retrospective analysis of patients admitted to the Intensive Care Unit between July 2007 and June 2009 who had AKI stage I. We collected fluid input, output, and haemodynamic data on day of AKI I and on day of AKI III (if AKI III developed) or 72 h after AKI I (if patients did not progress to AKI III). Univariable and multivariable logistic regression analyses were performed. RESULTS: Among 210 patients with AKI I (median age 70 y; 138 males), 85 had a subsequent mean fluid gain >1 L/day. Their risk of AKI III or death in intensive care unit was significantly higher compared with patients who gained <=1 L/day (63.5% vs. 23.3%, P = 0.001, and 43.5% vs. 24.8%, P = 0.004, respectively). AKI I patients who gained >1 L/day had a significantly lower urine output (50 vs. 66 mL/h, P = 0.02), lower mean arterial pressure (71 vs. 74 mmHg, P = 0.01), higher arterial lactate level (2.7 vs. 2.0 mmol/L, P < 0.001), and higher Sequential Organ Failure Assessment score (9.4 vs. 8.2, P = 0.002) on day of AKI I compared with those who gained <= 1 L/day. Multivariable analysis showed that only fluid intake was independently associated with progression to AKI III (OR 1.8 per 1 L; 95% CI 1.1 - 8.8; P = 0.02), but reduced urine output was not an independent risk factor (OR 0.8; 95% CI 0.3 - 2.2; P = 0.6). CONCLUSION: Increased fluid intake in early AKI was an independent risk factor for AKI III. PMID- 26263434 TI - Plasma-Mediated Gut Protection After Hemorrhagic Shock is Lessened in Syndecan-1 /- Mice. AB - We have shown in a rodent model of hemorrhagic shock (HS) that fresh frozen plasma (FFP) reduces lung inflammation and injury that are correlated with restitution of syndecan-1. As the gut is believed to contribute to distant organ injury and inflammation after shock, the current study sought to determine if the protective effects of plasma would extend to the gut and to elucidate the contribution of syndecan-1 to this protective effect. We also examined the potential role of TNFalpha, and a disintegrin and metalloproteinase (ADAM)-17, both intestinal sheddases of syndecan-1. Wild-type (WT) and syndecan-1 (KO) mice were subjected to HS followed by resuscitation with lactated Ringer's (LR) or FFP and compared with shock alone and shams. Small bowel and blood were obtained after 3 h for analysis of mucosal injury and inflammation and TNFalpha and ADAM 17 protein expression and activity. After HS, gut injury and inflammation were significantly increased compared with shams. Resuscitation with LR decreased both injury and inflammation that were further lessened by FFP. KO mice displayed worsened gut injury and inflammation after HS compared with WT mice, and LR and FFP equivalently inhibited injury and inflammation. Both systemic and intestinal TNFalpha and ADAM-17 followed similar trends, with increases after HS, reduction by LR, and a further decrease by FFP in WT but not KO mice. In conclusion, FFP decreased gut injury and inflammation after hemorrhagic shock, an effect that was abrogated in syndecan-1 mice. Plasma also decreased TNFalpha and ADAM-17, representing a potential mechanistic link to its protection via syndecan-1. PMID- 26263436 TI - Advances in Vascular Hyporeactivity After Shock: The Mechanisms and Managements. AB - Vascular reactivity to vasoconstrictors and vasodilators is greatly reduced after severe trauma, shock, and sepsis or multiple organ dysfunction syndrome. This reduced vascular reactivity severely interferes with the treatment of shock and other critical conditions. In particular, it interferes with the efficacy of vasoactive agents. Consequently, it is very important to elucidate the mechanisms and search for the effective treatment measures. In recent years, a lot of studies focused on the characteristics and the change rules of vascular hyporeactivity and mechanisms following shock. Also, the treatment approaches based on various mechanisms have been a hot pot these years. PMID- 26263437 TI - SIRTUIN 1 ACTIVATOR SRT1720 PROTECTS AGAINST ORGAN INJURY INDUCED BY INTESTINAL ISCHEMIA-REPERFUSION. AB - Intestinal ischemia-reperfusion (I/R) occurs in various clinical situations and causes local and remote organ injury, especially in the lungs, leading to significant morbidity and mortality. The maintenance of mitochondrial biogenesis is essential for cell survival and is regulated in part by sirtuin 1 (SIRT1), an energy-sensing enzyme. We hypothesized that SIRT1 activation with SRT1720 would reduce local and remote organ injury after intestinal I/R. Intestinal I/R was induced by the occlusion of the superior mesenteric artery of adult male C57BL/6 mice for 45 min, followed by reperfusion for 4 h. SRT1720 or vehicle was injected intravenously at the time of reperfusion. Blood, small intestine, and lung tissues were collected for analysis. The SRT1720 treatment of I/R mice resulted in a 57% increase in protein levels of succinate dehydrogenase, an index of mitochondrial mass, and a 120% increase in messenger RNA levels of mitochondrial transcription factor A, a marker for mitochondrial biogenesis. The microscopic architecture and apoptosis of the gut tissue was improved in the SRT1720-treated I/R mice. SRT1720 decreased intestinal messenger RNA levels of tumor necrosis factor-alpha by 60% and inducible nitric oxide synthase to baseline after I/R. Systemic inflammation, as determined by serum interleukin-6, was reduced in treated mice. Lung injury, as measured by histological architecture and myeloperoxidase activity, and lung apoptosis were also improved after the SRT1720 treatment. SRT1720 preserved mitochondrial biogenesis and mass, leading to inhibition of inflammation and oxidative stress, thereby protecting against intestinal I/R-induced injury. Thus, the SIRT1-mediated pathway is a promising target for the treatment of intestinal I/R injury. PMID- 26263438 TI - Skeletal Muscle Protein Breakdown Remains Elevated in Pediatric Burn Survivors up to One-Year Post-Injury. AB - Acute alterations in skeletal muscle protein metabolism are a well-established event associated with the stress response to burns. Nevertheless, the long lasting effects of burn injury on skeletal muscle protein turnover are incompletely understood. This study was undertaken to investigate fractional synthesis (FSR) and breakdown (FBR) rates of protein in skeletal muscle of pediatric burn patients (n = 42, >30% total body surface area burns) for up to 1 year after injury. Skeletal muscle protein kinetics were measured in the post prandial state following bolus injections of C6 and N phenylalanine stable isotopes. Plasma and muscle phenylalanine enrichments were quantified using gas chromatography-mass spectrometry. We found that the FSR in burn patients was 2- to 3-fold higher than values from healthy men previously reported in the literature (P <= 0.05). The FBR was 4- to 6-fold higher than healthy values (P < 0.01). Therefore, net protein balance was lower in burn patients compared with healthy men from 2 weeks to 12 months post-injury (P < 0.05). These findings show that skeletal muscle protein turnover stays elevated for up to 1 year after burn, an effect attributable to simultaneous increases in FBR and FSR. Muscle FBR exceeds FSR during this time, producing a persistent negative net protein balance, even in the post-prandial state, which likely contributes to the prolonged cachexia seen in burned victims. PMID- 26263439 TI - Low-Dose Heparin Anticoagulation During Extracorporeal Life Support for Acute Respiratory Distress Syndrome in Conscious Sheep. AB - BACKGROUND: Over 32% of burned battlefield causalities develop trauma-induced hypoxic respiratory failure, also known as acute respiratory distress syndrome (ARDS). Recently, 9 out of 10 US combat soldiers' survived life-threatening trauma-induced ARDS supported with extracorporeal membrane oxygenation (ECMO), a portable form of cardiopulmonary bypass. Unfortunately, the size, incidence of coagulation complications, and the need for systematic anticoagulation for traditional ECMO devices have prevented widespread use of this lifesaving technology. Therefore, a compact, mobile, ECMO system using minimal anticoagulation may be the solution to reduce ARDS in critically ill military and civilian patients. METHODS: We conducted a prospective cohort laboratory investigation to evaluate the coagulation function in an ovine model of oleic acid induced ARDS supported with veno-venous ECMO. The experimental design approximated the time needed to transport from a battlefield setting to an advanced facility and compared bolus versus standard heparin anticoagulation therapy. RESULTS: Comprehensive coagulation and hemostasis assays did not show any difference because of ECMO support over 10 h between the two groups but did show changes because of injury. Platelet count and function did decrease with support on ECMO, but there was no significant bleeding or clot formation during the entire experiment. CONCLUSIONS: A bolus heparin injection is sufficient to maintain ECMO support for up to 10 h in an ovine model of ARDS. With a reduced need for systematic anticoagulation, ECMO use for battlefield trauma could reduce significant morbidity and mortality from ventilator-induced lung injury and ARDS. Future studies will investigate the mechanisms and therapies to support patients for longer periods on ECMO without coagulation complications. LEVEL OF EVIDENCE: V--therapeutic animal experiment. PMID- 26263441 TI - WHAT'S NEW IN SHOCK? OCTOBER 2015. PMID- 26263440 TI - Adiponectin in Fresh Frozen Plasma Contributes to Restoration of Vascular Barrier Function After Hemorrhagic Shock. AB - Hemorrhagic shock is the leading cause of preventable deaths in civilian and military trauma. Use of fresh frozen plasma (FFP) in patients requiring massive transfusion is associated with improved outcomes. FFP contains significant amounts of adiponectin, which is known to have vascular protective function. We hypothesize that FFP improves vascular barrier function largely via adiponectin. Plasma adiponectin levels were measured in 19 severely injured patients in hemorrhagic shock (HS). Compared with normal individuals, plasma adiponectin levels decreased to 49% in HS patients before resuscitation (P < 0.05) and increased to 64% post-resuscitation (but not significant). In a HS mouse model, we demonstrated a similar decrease in plasma adiponectin to 54% but a significant increase to 79% by FFP resuscitation compared with baseline (P < 0.05). HS disrupted lung vascular barrier function, leading to an increase in permeability. FFP resuscitation reversed these HS-induced effects. Immunodepletion of adiponectin from FFP abolished FFP's effects on blocking endothelial hyperpermeability in vitro, and on improving lung vascular barrier function in HS mice. Replenishment with adiponectin rescued FFP's effects. These findings suggest that adiponectin is an important component in FFP resuscitation contributing to the beneficial effects on vascular barrier function after HS. PMID- 26263442 TI - Underuse of anticoagulation in stroke patients with atrial fibrillation--the FibStroke Study. AB - BACKGROUND AND PURPOSE: Current guidelines recommend oral anticoagulation (OAC) for patients with atrial fibrillation (AF) and increased risk of thromboembolic events. The reasons for not using OAC in AF patients suffering stroke or transient ischaemic attack (TIA) were assessed. METHODS: This retrospective registry included 3404 patients with previously diagnosed AF who suffered a total of 2955 ischaemic strokes and 895 TIAs during 2003-2012. RESULTS: A CHA2DS2-VASc score >=2 and a CHADS2 score >=2 was observed in 3590 (93.2%) and in 2784 (72.3%) of the events, respectively. Of the high-risk patients (CHADS2 >=2) only 55.1% were on OAC before the onset of stroke or TIA. The most frequently documented reasons for withholding OAC were infrequent paroxysms of AF (14%), previous bleeding episodes (13%) and the patient's decline/independent discontinuation of treatment (9%). Moreover, patients with paroxysmal AF (40% using OAC), previous bleeding (26% using OAC) and alcohol abuse (30% using OAC) were using OAC significantly less often than patients without these characteristics. A significant increase in the proportion of high-risk patients using OAC from 49% in 2003 to 65% in 2012 was seen. CONCLUSIONS: Underuse of anticoagulation is a common contributor to ischaemic strokes and TIA episodes in patients with AF. Infrequent AF episodes, previous bleeds, patient preference and alcohol abuse were the most common reasons for not using OAC. PMID- 26263443 TI - Interactions between local dilator and sympathetic vasoconstrictor influences in skeletal muscle in acute and chronic hypoxia. AB - NEW FINDINGS: What is the topic of this review? This review considers how local dilator mechanisms and increased sympathetic nerve activity interact during acute systemic hypoxia and then reviews current understanding of some of the modifications induced by chronic hypoxia. What advances does it highlight? During acute hypoxia, local levels of hypoxia determine the release of vasodilators and magnitude of arteriolar dilatation, as well as the extent to which sympathetically evoked vasoconstriction is blunted, so maximizing distribution of O2 to muscle fibres. Chronic hypoxia in adult life and fetal programming induced by chronic hypoxia in utero lead to increased responsiveness to acute hypoxia and further blunting of sympathetic vasoconstriction, but are also associated with hypertension. In resting skeletal muscle, acute systemic hypoxia evokes vasodilatation, while vasoconstriction evoked by increased muscle sympathetic nerve activity is blunted, referred to herein as hypoxic sympatholysis. This review considers the contributions of adenosine, prostaglandin I2 , nitric oxide, ATP and endothelium-derived hyperpolarizing factors to the muscle vasodilatation, with particular attention being given to the release and actions of adenosine, which plays a dominant role. It is argued that the dilator substances are released in proportion to the local level of hypoxia, notably, allowing terminal arterioles to regulate O2 distribution through the capillaries. Correspondingly, hypoxic sympatholysis can be attributed to the ability of local hypoxia to blunt vasoconstriction evoked by noradrenaline acting on alpha1 - and alpha2 adrenoceptors. The synergistic actions of ATP as cotransmitter may be depressed in parallel, but the actions of neuropeptide Y persist. Consideration is also given to the changes induced by chronic hypoxia in adult life and to the consequences in adult life of fetal programming induced by chronic hypoxia during pregnancy. In both conditions, dilator responsiveness to acute hypoxia is maintained, but the action or release of adenosine is altered in ways that are not yet understood. Both conditions are also accompanied by blunted sympathetically evoked vasoconstriction, tonically raised muscle sympathetic nerve activity, and increased muscular vascular tone and arterial blood pressure. With hypoxia-induced fetal programming, arterial pressure is increased in young adults and increases with age. The mechanisms underlying these changes are discussed, and it is argued that chronic hypoxia in adult life or in utero may facilitate development of hypertension. PMID- 26263444 TI - The Cost of Scientific Misconduct. PMID- 26263445 TI - American Pediatric Society 2015 Presidential Address: leaky pipes, glass ceilings, and changing landscapes-time to renovate the pediatric house. AB - Presented at the PAS Annual Meeting, 25-28 April 2015, San Diego, CA. PMID- 26263446 TI - Intrinsically disordered amphiphilic peptides as potential targets in drug delivery vehicles. AB - Intrinsically disordered proteins/peptides play a crucial role in many physiological and pathological events and may assume a precise conformation upon binding to a specific target. Recently, we have described the conformational and functional properties of two linear ester peptides provided with the following sequences: Y-G-E-C-P-C-K-OAllyl (PepK) and Y-G-E-C-P-C-E-OAllyl (PepE). Both peptides are characterized by the presence of the "CPC" motif together with a few amino acids able to promote disorder. The CPC sequence is a binding motif for the CXCR4 receptor that represents a well-known target for cancer therapies. In this paper, we report on synthetic amphiphilic peptides that consist of lipophilic derivatives of PepE and PepK bearing two stearic alkyl chains and/or an ethoxylic spacer. These peptide amphiphiles form stable supramolecular aggregates; they present conformational features that are typical of intrinsically disordered molecules as shown by CD spectroscopy. Solution fluorescence and DLS studies have been performed to evaluate Critical Micellar Concentrations and the dimension of supramolecular aggregates. Moreover, preliminary in vitro cell-based assays have been conducted to investigate the molecular recognition processes involving the CXCR4 receptor. In the end, the results obtained have been compared with the previous data generated by the corresponding non-amphiphilic peptides (PepE and PepK). PMID- 26263447 TI - Atypical gunshot wound: Bullet trajectory analyzed by computed tomography. AB - INTRODUCTION: Gunshot injuries are a result of a bullet or projectile fired from a weapon that penetrates the body. Homicide, suicide, and occasionally, accidental events are a significant cause of firearm-related injuries. In rare cases, the damage from the gunshot injury can be masked due to an atypical bullet trajectory. PRESENTATION OF CASE: A 63-year-old male was found with a gunshot wound to the anterior left knee. Computed tomography (CT) scans revealed a bullet track extending from the anterior aspect of the left knee that traveled cephalad subcutaneously and entered into the peritoneal cavity, perforating the distal descending colon. The bullet was found to be at rest adjacent to the spleen and posterior chest wall, with no injury to the lungs, kidneys or the spleen. The patient required a sigmoid colectomy with descending colostomy and was subsequently discharged home without any complications. DISCUSSION: Intra abdominal organ damage from a gunshot wound to the distal limb is a rare occurrence. Atypical gun shot wounds, such as this case, have the potential for multiple issues including: delayed diagnostic tests, inaccurate radiological readings, and inappropriate medical management. CONCLUSION: If an abnormal trajectory is maintained, it is possible for a bullet to traverse half the length of the body without the patient realizing it. Accurate CT analysis and quick decisions in surgical and medical management are critical takeaways to provide quality care to patients with these injuries. PMID- 26263448 TI - Laparoscopic repair of a bilateral internal inguinal hernia with supravesical hernia - a case report. AB - INTRODUCTION: Supravesical hernia is an exceptional subtype of internal inguinal hernia, and it is located between the median umbilical ligament and the medial umbilical ligament. The hernia is classified as two types: internal supravesical hernia and external supravesical hernia. PRESENTATION OF CASE: Herein we report a rare case of external supravesical hernia successfully treated by laparoscopic procedure. The patient who complained right inguinal protrusion and mild frequent urination was diagnosed as right inguinal hernia and potential of left inguinal hernia using computed tomography. He underwent laparoscopic bilateral hernia repair, and intraoperative findings revealed right external supravesical hernia and left internal inguinal hernia. DISCUSSION: Laparoscopic hernia repair may make it possible to avoid overlooking of internal hernia such as supravesical hernia. Moreover it was possible to cover the hernia orifice and dissected layer of the dorsal site of urine bladder using bilateral approach in the current case. CONCLUSION: In conclusions, laparoscopic hernia repair might be a surgical option for supravesical hernia. PMID- 26263449 TI - A novel technique for securing tracheal blood supply in salvage anterior mediastinal tracheostomy. AB - INTRODUCTION: The only way for complete cure of advanced esophageal cancer with invasion to the mid-trachea is anterior mediastinal tracheostomy (AMT), which has a significantly high risk of fatal complications. The shorter tracheal stump is beneficial for good blood supply, but complicates to create a tracheostomy. PRESENTATION OF CASE: A 71-year-old patient with a history of advanced cervical esophageal cancer who was treated with definitive chemoradiotherapy 3 years earlier had local recurrence on the left side of the trachea despite salvage lymphadenectomy for solitary left paratracheal lymph node recurrence 1 year earlier. AMT involving a resection of nearly the whole trachea was needded for complete resection. However, the recurrenced tumor was localized on the tracheal left side. We designed the new surgical procedure to preserve a longer segment of the unaffected right tracheal wall by diagonal cut (3.6cm longer than on the left side) while maintaining adequate blood flow by preserving the right lateral vascular pedicle in a state of connecting with the right lobe of the thyroid gland and the right tracheal stump. The postoperative course was uneventful, and at 1 year postoperatively, no tumor recurrence has been detected. DISCUSSION: Preservation of the lateral vascular pedicle enables a longer tracheal stump by securing sufficient blood supply and a longer tracheal stump in AMT, even when unilateral, enables to create tracheostomy more surely, preventing fatal complications. CONCLUSION: This novel procedure should be considered in cases with tumor invasion extending into the lower mid-trachea that is limited to one side. PMID- 26263451 TI - Emphysematous gastritis in a patient with coxsackie B3 myocarditis and cardiogenic shock requiring veno-arterial extra-corporeal membrane oxygenation. AB - INTRODUCTION: Emphysematous gastritis is a rare condition in which gas accumulates in the stomach lining usually due to an infectious source. CASE PRESENTATION: We present a 16 year old female with viral myocarditis and cardiogenic shock transferred to our hospital on extracorporeal membrane oxygenation (ECMO) who developed emphysematous gastritis. After listing the patient for heart transplant, patient underwent Bi-VAD placement requiring veno venous ECMO support. Subsequently, she developed worsening abdominal distention. CT of abdomen/pelvis showed the stomach to be diffusely edematous, thick-walled, containing intramural gas collections, consistent with emphysematous gastritis. Patient underwent nonoperative management and two weeks later had complete resolution of the gastritis. Unfortunately, her overall condition deteriorated in the subsequent days and support was withdrawn. DISCUSSION: Management of emphysematous gastritis usually revolves around supportive care, broad spectrum antibiotics and bowel rest. Our patients' gastritis resolved with non-operative management, albeit, she succumbed to multiorgan failure due to other causes. CONCLUSION: We believe, this is a unique case of a veno-arterial ECMO causing emphysematous gastritis. PMID- 26263450 TI - A rare combination between familial multiple lipomatosis and extragastrointestinal stromal tumor. AB - INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Rarely, GISTs can be located in mesentery, retroperitoneal space, omentum or pancreas. In these cases, the neoplasm is defined as "extra-gastrointestinal stromal tumors" (EGISTs). PRESENTATION OF CASE: We reported a case of a 63-year-old male patient diagnosed by computer tomography with large intraabdominal tumor with vague origin, postoperatively determined as an EGIST. The diagnosis was confirmed by immunohistochemical study. The patient had multiple, subcutaneous, painless lipomas localized in the arms, forearms, thighs, abdomen and thorax. Because of the family history and the clinical presentation the disease was determined as familial multiple lipomatosis (FML). We performed radical tumor resection with distal pancreatectomy and splenectomy, and abdominoplasty, removing redundant skin and underlying subcutaneous fat tissue with multiple lipomas. DISCUSSION: FML is a rare hereditary benign disease. On the other hand, only few cases with familial GIST have been reported. In cases with extensive abdominal involvement, the primary origin of EGIST may be impossible to determine so the differential diagnosis is very difficult. CONCLUSION: Although we could not prove correlation between the observed diseases, they are extremely rare and their combination is unusual which makes the presented case valuable and interesting. PMID- 26263452 TI - Traumatic avulsion of tibialis anterior following an industrial accident: A case report. AB - INTRODUCTION: Rupture of the tibialis anterior tendon is uncommon and can occur spontaneously or following trauma. If suspected, it should be diagnosed promptly, enabling early surgical management and good restoration of function. PRESENTATION OF CASE: A 48 year old male sustained a crush injury to his right foot when it became stuck in a vertical industrial fan at work. He attended A & E complaining of swelling of the dorsum of foot. On examination, there was tenderness at the base of the first metatarsal. X-ray revealed an avulsion fracture of the first metatarsal, and MRI showed rupture of tibialis anterior. The patient underwent surgical repair 10 days later, with post-operative management in a non-weight bearing, then weight bearing cast. X-ray at 8 weeks showed that the fracture had healed. The patient had a course of physiotherapy and was followed up at 6 months to assess pain and function. DISCUSSION: Tibialis anterior rupture should be considered if the history is suggestive, and can be diagnosed clinically based on the triad of a 'pseudotumour' of the ruptured tendon, loss of tendon contour, and reduced dorsiflexion of the ankle. In our case, the avulsion fracture prompted further imaging to confirm the diagnosis and plan surgery. There are various operative technique described in the literature. We used a whip stitch with anchors to reattach the tendon to the base of first metatarsal. CONCLUSION: A prompt and early diagnosis of surgical repair of tibialis anterior tendon avulsion is important to ensure that the patients return to work as an industrial worker. PMID- 26263453 TI - An unusual case of duodenal perforation caused by a blister pack: A case report and literature review. AB - INTRODUCTION: Ingestion of foreign bodies is a relatively common clinical problem. Blister packs have been known to be a causative agent of gastrointestinal perforation. We report a rare case of duodenal perforation caused by a blister pack, which was complicated by retroperitoneal abscess and having a poor outcome. PRESENTATION OF CASE: A 72 year-old man with a history of dementia presented to the emergency department with a 2-day history of backache. Upon radiological findings, perforated peptic ulcer was suspected. However, emergency laparotomy revealed a blister pack protruding from the posterior wall of the third portion of the duodenum. It was complicated by a widespread retroperitoneal abscess. After removal of the foreign body, the perforation was treated with primary suture repair and an omental patch. However, the patient died two days after operation due to sepsis. DISCUSSION: According to a literature review, the ileum is the most common site of perforation caused by blister packs. To our knowledge, duodenal perforations have not been documented to date. Curative treatment often involves emergent surgery. However, duodenal perforation in the third portion may lead to retroperitoneal abscess, which can result in severe sepsis and have a poor outcome. As there is no consensus about an ideal surgical approach, retroperitoneal abscess is one of the clinical challenges for surgeons. Even with prompt management, duodenal perforation may become fatal. CONCLUSION: Unnoticed ingestion of blister packs can cause duodenal perforation. Although prompt management is necessary, duodenal perforation, especially in the third portion, may be potentially fatal. PMID- 26263454 TI - Ferroelectric Polymer Matrix for Probing Molecular Organization in Perylene Diimides. AB - Ferroelectric films of poly(vinylidene fluoride-co-trifluoroethylene) (PVDF-TrFE) provide a controlled environment to study the aggregation tendency of functional molecules such as perylene diimides (PDIs). The local electric field and free volume confinement parameters offered by the matrix are tailored to study the organizational and assembly characteritics of molecular acceptors. The optical properties of planar and nonplanar PDIs in the ferroelectric polymer matrix were studied systematically over a wide range that encompassed the ferroelectric transition temperature. This approach provides valuable insight into the properties of molecular materials used in applications ranging from bulk heterostructure-based photovoltaics to nonlinear optical materials. PMID- 26263455 TI - Palladium Nanoparticle-Loaded Cellulose Paper: A Highly Efficient, Robust, and Recyclable Self-Assembled Composite Catalytic System. AB - We present a novel strategy based on the immobilization of palladium nanoparticles (Pd NPs) on filter paper for development of a catalytic system with high efficiency and recyclability. Oleylamine-capped Pd nanoparticles, dispersed in an organic solvent, strongly adsorb on cellulose filter paper, which shows a great ability to wick fluids due to its microfiber structure. Strong van der Waals forces and hydrophobic interactions between the particles and the substrate lead to nanoparticle immobilization, with no desorption upon further immersion in any solvent. The prepared Pd NP-loaded paper substrates were tested for several model reactions such as the oxidative homocoupling of arylboronic acids, the Suzuki cross-coupling reaction, and nitro-to-amine reduction, and they display efficient catalytic activity and excellent recyclability and reusability. This approach of using NP-loaded paper substrates as reusable catalysts is expected to open doors for new types of catalytic support for practical applications. PMID- 26263456 TI - Femto- to Microsecond Photodynamics of an Unusual Bacteriophytochrome. AB - A bacteriophytochrome from Stigmatella aurantiaca is an unusual member of the bacteriophytochrome family that is devoid of hydrogen bonding to the carbonyl group of ring D of the biliverdin (BV) chromophore. The photodynamics of BV in SaBphP1 wild type and the single mutant T289H reintroducing hydrogen bonding to ring D show that the strength of this particular weak interaction determines excited-state lifetime, Lumi-R quantum yield, and spectral heterogeneity. In particular, excited-state decay is faster in the absence of hydrogen-bonding to ring D, with excited-state half-lives of 30 and 80 ps for wild type and the T289H mutant, respectively. Concomitantly, the Lumi-R quantum yield is two times higher in wild type as compared with the T289H mutant. Furthermore, the spectral heterogeneity in the wild type is significantly higher than that in the T289H mutant. By extending the observable time domain to 25 MUs, we observe a new deactivation pathway from the Lumi-R intermediate in the 100 ns time domain that corresponds to a backflip of ring D to the original Pr 15Za isomeric state. PMID- 26263457 TI - Ab Initio Analysis of Auger-Assisted Electron Transfer. AB - Quantum confinement in nanoscale materials allows Auger-type electron-hole energy exchange. We show by direct time-domain atomistic simulation and analytic theory that Auger processes give rise to a new mechanism of charge transfer (CT) on the nanoscale. Auger-assisted CT eliminates the renown Marcus inverted regime, rationalizing recent experiments on CT from quantum dots to molecular adsorbates. The ab initio simulation reveals a complex interplay of the electron-hole and charge-phonon channels of energy exchange, demonstrating a variety of CT scenarios. The developed Marcus rate theory for Auger-assisted CT describes, without adjustable parameters, the experimental plateau of the CT rate in the region of large donor-acceptor energy gap. The analytic theory and atomistic insights apply broadly to charge and energy transfer in nanoscale systems. PMID- 26263458 TI - Correction to "Phase Behavior and Percolation Properties of the Patchy Colloidal Fluids in the Random Porous Media". PMID- 26263459 TI - Introducing Perovskite Solar Cells to Undergraduates. PMID- 26263460 TI - Elemental Selenium for Electrochemical Energy Storage. AB - To meet the increasing demand for electrochemical energy storage with high energy density, elemental Se is proposed as a new attractive candidate with high volumetric capacity density similar to that of S. Se is chemically and electrochemically analogous to S to a large extent but is saliently featured owing to its semiconductivity, compatibility with carbonate-based electrolytes, and activity with a Na anode. Despite only short-term studies, many advanced Se based electrode materials have been developed for rechargeable Li batteries, Na batteries, and Li ion batteries. In this Perspective, we review the advances in Se-based energy storage materials and the challenges of Li-Se battery in both carbonate-based and ether-based electrolytes. We also discuss the rational design strategies for future Se-based energy storage systems based on the strengths and weaknesses of Se. PMID- 26263461 TI - Long-Distance Sequential Charge Separation at Micellar Interface Mediated by Dynamic Charge Transporter: A Magnetic Field Effect Study. AB - Construction of photogenerated long-lived charge-separated states is crucial for light-energy conversion using organic molecules. For realization of cheap and easy-to-make long-distance electron transfer (ET) systems, we have developed a supramolecular donor(D)-chromophore(C)-acceptor(A) triad utilizing a micellar interface. Alkyl viologen (A(2+)) is adsorbed on the hydrophilic interface of Triton X-100 micelle, which bears D units in the hydrophobic core. Excited triplet state of a hydrophobic flavin C entrapped in the supercage gives rise to primary ET from D, which is followed by the secondary ET from C(-*) to A(2+) to give the long-lived (>10 MUs) charge-separated state with negligible yield of escaped C(-*). Analysis of magnetic field effect reveals that diffusion of C(-*) from the core to the hydrophilic interface leads to long-distance ET with a low charge recombination yield of ~20%. This novel concept of "dynamic charge transporter" has important implications for development of photon-energy conversion systems in solution phase. PMID- 26263462 TI - Unveiling the Janus-Like Properties of OH(-). AB - Using ab initio simulations, we explore the glassy landscape of the OH(-)(H2O)20 cluster and its infrared spectrum. We show that the OH(-) has an amphiphilic Janus-type behavior like the hydronium ion induced by the ability of its O-H bond to be buried inside of the cluster or exposed at the surface with different coordination numbers. Recent infrared experiments of aqueous NaOH have found two pronounced peaks at 2000 and 2850 cm(-1) [Mandal, A.; J. Chem. Phys. 2014, 140, 1 12]. The microscopic origins of these spectral features remain elusive. Herein, we disentangle the contribution of the spectra between 1700 and 3000 cm(-1) in terms of the microscopic solvation structure of OH(-) and dub this as the amphiphilic band. The delocalized nature of OH(-) results in a red shift to the O H stretch, which mixes with bend-vibrations, the extent to which is tuned by the local coordination number. These results have important bearing on understanding the spectroscopic signatures of OH(-) in environments like the air-water interface. PMID- 26263463 TI - Perovskite Solar Cells: Do We Know What We Do Not Know? PMID- 26263464 TI - Accelerating Electrolyte Discovery for Energy Storage with High-Throughput Screening. AB - Computational screening techniques have been found to be an effective alternative to the trial and error of experimentation for discovery of new materials. With increased interest in development of advanced electrical energy storage systems, it is essential to find new electrolytes that function effectively. This Perspective reviews various methods for screening electrolytes and then describes a hierarchical computational scheme to screen multiple properties of advanced electrical energy storage electrolytes using high-throughput quantum chemical calculations. The approach effectively down-selects a large pool of candidates based on successive property evaluation. As an example, results of screening are presented for redox potentials, solvation energies, and structural changes of ~1400 organic molecules for nonaqueous redox flow batteries. Importantly, on the basis of high-throughput screening, in silico design of suitable candidate molecules for synthesis and electrochemical testing can be achieved. We anticipate that the computational approach described in this Perspective coupled with experimentation will have a significant role to play in the discovery of materials for future energy needs. PMID- 26263466 TI - Beyond Lithium Ion Batteries. PMID- 26263465 TI - Fast Solid-State Li Ion Conducting Garnet-Type Structure Metal Oxides for Energy Storage. AB - Lithium ion batteries are the most promising energy storage system on the market today; however, safety issues associated with the use of flammable organic polymer-based electrolytes with poor electrochemical and chemical stabilities prevent this technology from reaching maturity. Solid lithium ion electrolytes (SLIEs) are being considered as potential replacements for the organic electrolytes to develop all-solid-state Li ion batteries. Out of the recently discovered SLIEs, the garnet-related structured Li-stuffed metal oxides are the most promising electrolytes due to their high total (bulk + grain boundary) Li ion conductivity, high electrochemical stability window (~6 V versus Li(+)/Li at room temperature), and chemical stability against reaction with an elemental Li anode and high-voltage metal oxide Li cathodes. This Perspective discusses the structural-chemical composition-ionic conductivity relationship of Li-stuffed garnets, followed by a discussion on the Li ion conduction mechanism, as well as the electrochemical and chemical stability of these materials. The performance of a number of all-solid-state batteries employing garnet-type Li ion electrolytes is also discussed. PMID- 26263467 TI - The Band Gap of Graphene Is Efficiently Tuned by Monovalent Ions. AB - Small monovalent ions are able to polarize carbonaceous nanostructures significantly. We report a systematic investigation of how monovalent and divalent ions influence valence electronic structure of graphene. Pure density functional theory is employed to compute electronic energy levels. We show that the lowest unoccupied molecular orbital (LUMO) of an alkali ion (Li(+), Na(+)) fits between the highest occupied molecular orbital (HOMO) and LUMO of graphene, in such a way as to tune the bottom of the conduction band (i.e., band gap). In turn, Mg(2+) shares its orbitals with graphene. The corresponding binding energy is ca. 4 times higher than that in the case of alkali ions. The reported insights provide inspiration for engineering electrical properties of the graphene containing systems. PMID- 26263468 TI - TiO2(110) Charge Donation to an Extended pi-Conjugated Molecule. AB - The surface reduction of rutile TiO2(110) generates a state in the band gap whose excess electrons are spread among multiple sites, making the surface conductive and reactive. The charge extraction, hence the surface catalytic properties, depends critically on the spatial extent of the charge redistribution, which has been hitherto probed by small molecules that recombine at oxygen vacancy (Ovac) sites. We demonstrate by valence band resonant photoemission (RESPES) a very general charge extraction mechanism from a reduced TiO2(110) surface to an extended electron-acceptor organic molecule. Perylene-tetra-carboxylic-diimide (PTCDI) is not trapped at Ovac sites and forms a closely packed, planar layer on TiO2(110). In this configuration, the perylene core spills out the substrate excess electrons, filling the lowest unoccupied molecular orbital (LUMO). The charge transfer from the reduced surface to an extended pi-conjugated system demonstrates the universality of the injection/extraction mechanism, opening new perspectives for the coupling of reducible oxides to organic semiconductors and supported catalysts. PMID- 26263469 TI - Lipocalin-2 Is a Disease Activity Marker in Inflammatory Bowel Disease Regulated by IL-17A, IL-22, and TNF-alpha and Modulated by IL23R Genotype Status. AB - BACKGROUND: Lipocalin-2 (LCN2) is a potent bacteriostatic protein. We aimed to investigate its role as a disease activity marker in patients with inflammatory bowel disease (IBD) and its induction by the Th17 cytokines IL-17A, IL-22, and TNF-alpha in colonic epithelial cells. Moreover, we analyzed the influence of IBD associated IL23R alleles on LCN2 serum levels in IBD patients. METHODS: LCN2 serum levels were determined in 131 IBD patients (71 with Crohn's disease [CD], 60 with ulcerative colitis [UC]) and 63 healthy controls. IBD patients were genotyped for 10 IBD-associated IL23R polymorphisms. LCN2 expression after stimulation with IL-17A, IL-22, and TNF-alpha was measured in human colonic epithelial cell lines. RESULTS: A significant upregulation of serum LCN2 in active IBD (median [IQR], 36.84 [21.17-73.74] ng/mL; P = 0.01) compared with healthy controls (24.22 [17.76-35.25] ng/mL) was confined to active UC (42.21 [28.97-73.74] ng/mL; P = 0.0006). LCN2 proved to be a marker of UC disease activity (area under the curve 0.75, sensitivity 0.83, specificity 0.63; P = 0.0002). IL-17A showed a synergistic effect with IL-22 and TNF-alpha in inducing colonic epithelial expression of LCN2 and its essential transcription factor IKBZ. In CD, LCN2 concentrations were significantly modulated by IL23R genotype status with homozygous carriers of IBD risk-increasing alleles showing particularly low LCN2 levels. CONCLUSIONS: Serum LCN2 proves to be a biomarker of active UC. Lower LCN2 levels in CD patients carrying IBD risk-increasing IL23R variants may result from a restricted upregulation of LCN2 due to an impaired Th17 immune response. PMID- 26263471 TI - Update on Charcot-Marie-Tooth disease. AB - PURPOSE OF REVIEW: Charcot-Marie-Tooth disease (CMT) is the common terminology used to describe the hereditary neuropathies. This update reviews advances in the past year in our understanding of these diseases, including some important earlier references. RECENT FINDINGS: In the past year, advances in next generation sequencing continued to increase the number of genes associated with CMT. The connection between genotype and phenotype has become more complicated. New insights into the pathogenesis of the diseases are reviewed. Treatment and clinical trial updates coming from these new insights, as well as use of high throughput screening to match potential treatments with targets, are moving the field forward. There is a discussion of potential next steps, including the use of patient-derived induced pluripotent stem cells, to enhance our understanding of individual genotypes and phenotypes. SUMMARY: The use of high-throughput screens, and techniques such as RNAi and induced pluripotent stem cell continue to push forward other therapies for specific genetic forms of CMT and are potentially more generalizable to peripheral neuropathies. These developments, along with the development of improved outcome measures and longitudinal natural history data, advance CMT, making the future for finding treatments and/or cures closer than it has ever been. PMID- 26263472 TI - Autoimmune inflammatory neuropathies: updates in pathogenesis, diagnosis, and treatment. AB - PURPOSE OF REVIEW: The present review aims at discussing the recent advances in pathogenesis, diagnosis, and treatment of major subtypes of autoimmune inflammatory neuropathies. RECENT FINDINGS: Concerning pathogenesis, further evidence has proved that antibodies to nodal proteins are pathogenic in inflammatory neuropathies. The presence of these antibodies is related to distinctive clinical features. Disruption of blood-nerve barrier mediated by cytokines and chemokines also plays an important role in the pathogenesis. The new terminology of 'nodopathies' describes immune-mediated attack beginning and limited to the nodal region, and this phenomenon can be found in both acute and chronic inflammatory neuropathies. Recent trials comparing intravenous and subcutaneous immunoglobulin confirm that subcutaneous immunoglobulin is not only cost-effective, but also improves patients' satisfaction and quality of life compared to intravenous immunoglobulin. Although immunotherapies are effective in most of the inflammatory neuropathies, accurate predictors and biomarkers of treatment response are lacking. Moreover, some patients do not respond to current immunotherapies and continue to relapse after discontinuation of treatment. SUMMARY: More studies are required to understand the exact antigenic targets and mechanism in inflammatory neuropathies, so as to develop more novel immunotherapies. PMID- 26263474 TI - Paranodal and other autoantibodies in chronic inflammatory neuropathies. AB - PURPOSE OF REVIEW: Autoimmune disorders of the peripheral nerves are diverse and heterogeneous. T cells, macrophages, and autoantibodies have been implicated in their pathogenesis. Autoantibodies to peripheral nerve molecules seem to play a role not only in the pathogenesis but provide diagnostic, prognostic, and therapeutic help. We review the state of the art and most relevant recent findings regarding autoantibodies in chronic inflammatory neuropathies, focusing on their clinical utility. RECENT FINDINGS: Research on autoantibodies in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) has received a recent boost with the description of antibodies against proteins of the node of Ranvier. Antibodies of the IgG4 isotype targeting the paranodal proteins contactin-1 (CNTN1) and neurofascin-155 (NF155) define specific CIDP subtypes and have diagnostic and prognostic implications. In multifocal motor neuropathy, anti-GM1 production is restricted to very few B-cell clones that could be the target of therapies aimed to remove or inactivate them. Moreover, novel ELISA and glycoarray techniques combining GM1 and galactocerebroside gangliosides improved the sensitivity of autoantibody detection. Detailed clinical and paraclinical features, including autoantibody reactivity patters, of autoimmune syndromes affecting simultaneously the central and peripheral nervous systems, are also described. SUMMARY: The heterogeneity of chronic inflammatory neuropathies is being unraveled with the description of specific autoantibodies and their association with small disease subtypes. The recently described paranodal autoantibodies anti-CNTN1 and NF155 have direct clinical value and seem to determine response to treatment. Further studies are needed to fully understand the primary contribution of the antibodies to the pathophysiology of the immune neuropathies. PMID- 26263473 TI - Modifier genes and their effect on Duchenne muscular dystrophy. AB - PURPOSE OF REVIEW: Recently, genetic pathways that modify the clinical severity of Duchenne muscular dystrophy (DMD) have been identified. The pathways uncovered as modifiers are useful to predict prognosis and also elucidate molecular signatures that can be manipulated therapeutically. RECENT FINDINGS: Modifiers have been identified using combinations of transcriptome and genome profiling. Osteopontin, encoded by the SPP1 gene, was found using gene expression profiling. Latent TGFbeta binding protein 4, encoding latent TGFbeta binding protein 4 was initially discovered using a genome-wide screen in mice and then validated in cohorts of DMD patients. These two pathways converge in that they both regulate TGFbeta. A third modifier, Anxa6 that specifies annexin A6, is a calcium binding protein that has been identified using mouse models, and regulates the injury pathway and sarcolemmal resealing. SUMMARY: Genetic modifiers can serve as biomarkers for outcomes in DMD. Modifiers can alter strength and ambulation in muscular dystrophy, and these same features can be used as endpoints used in clinical trials. Moreover, because genetic modifiers can influence outcomes, these genetic markers should be considered when stratifying results in muscular dystrophy. PMID- 26263475 TI - Recent advances in outcome measures in IgM-anti-MAG+ neuropathies. AB - PURPOSE OF REVIEW: This review aims to provide an overview of all randomized trials performed in IgM Anti-Myelin Associated Glycoprotein related peripheral neuropathy (MGUSP) with emphasis on the applied outcome measures including the rationale for their choice and possible limitations, emphasizing new advances in modern clinimetrics. RECENT FINDINGS: All clinical trials performed in patients with MGUSP have been negative, which raises many unanswered questions: were the sample sizes too small, the duration of the trials too short, the chosen medical interventions not aggressive enough, the definition of being a responder inadequate, and, last but not least, the outcome measures used improper? Only recently has attention been directed towards the possibility of using suboptimal outcome measures as a potential factor that may have contributed to the negative results in MGUSP. SUMMARY: Since there is no international consensus on how to assess and treat patients with MGUSP, the current study addresses new advances in the field of modern clinimetrics and recommendations for future outcome measure studies in MGUSP before proceeding with new interventional trials. PMID- 26263476 TI - Viral vector-mediated gene therapies. AB - PURPOSE OF REVIEW: Gene therapy as a treatment for neuromuscular disease has significantly advanced over the past decade. In the present review, the progress of adeno-associated viruses (AAV) vector-mediated gene therapy for Duchenne muscular dystrophy (DMD) during the past year is highlighted. RECENT FINDINGS: Modulating the immune response to AAV vector capsid or the transgene has helped to increase stable transduction efficiency. Full-length dystrophin expression via gene editing with targeted nucleases may ultimately be an ideal treatment option. Also genes with homologues function may ameliorate many aspects of the DMD pathophysiology. SUMMARY: The work during the past year has increased our understanding of AAV vector-mediated therapy and has also validated new approaches to treat DMD. The results will aid in the design of both preclinical and clinical trials. PMID- 26263477 TI - Photoelectrochemical Hydrogen Production of TiO2 Passivated Pt/Si-Nanowire Composite Photocathode. AB - Si nanowire (SiNW) arrays decorated with Pt nanoparticles are passivated with TiO2 surface layer using atomic layer deposition (ALD). The sandwich structure TiO2/Pt/SiNW shows superior photoelectrochemical performance to the control planar silicon electrodes, especially under the concentrated solar radiation. Pt nanoparticles separated from aqueous electrolyte by TiO2 layer of more than 15 nm still well catalyze surface photoelectrochemical hydrogen production without direct contact to the electrolyte. This structural configuration shows remarkable chemical stability and anodically shifted onset potential, suggesting great promise for applications in solar hydrogen production. The maximum photon-to energy conversion efficiency of the TiO2/Pt/SiNW reaches 15.6%. PMID- 26263478 TI - Comment on 'Impact of intra-arterial chemotherapy including internal carotid artery for advanced paranasal sinus cancers involving the skull base'. PMID- 26263479 TI - A Bayesian adaptive design for biomarker trials with linked treatments. AB - BACKGROUND: Response to treatments is highly heterogeneous in cancer. Increased availability of biomarkers and targeted treatments has led to the need for trial designs that efficiently test new treatments in biomarker-stratified patient subgroups. METHODS: We propose a novel Bayesian adaptive randomisation (BAR) design for use in multi-arm phase II trials where biomarkers exist that are potentially predictive of a linked treatment's effect. The design is motivated in part by two phase II trials that are currently in development. The design starts by randomising patients to the control treatment or to experimental treatments that the biomarker profile suggests should be active. At interim analyses, data from treated patients are used to update the allocation probabilities. If the linked treatments are effective, the allocation remains high; if ineffective, the allocation changes over the course of the trial to unlinked treatments that are more effective. RESULTS: Our proposed design has high power to detect treatment effects if the pairings of treatment with biomarker are correct, but also performs well when alternative pairings are true. The design is consistently more powerful than parallel-groups stratified trials. CONCLUSIONS: This BAR design is a powerful approach to use when there are pairings of biomarkers with treatments available for testing simultaneously. PMID- 26263480 TI - Is it the creatine or the anabolic androgenic steroids? Need for assessing the steroids role in testicular cancer. PMID- 26263481 TI - Macrophage subtype predicts lymph node metastasis in oesophageal adenocarcinoma and promotes cancer cell invasion in vitro. AB - BACKGROUND: Currently, there is a lack of ideal biomarkers for predicting nodal status in preoperative stage of oesophageal adenocarcinoma (EAC) to aid optimising therapeutic options. We studied the potential of applying subtype macrophages to predict lymph node metastasis and prognosis in EAC. MATERIAL AND METHODS: Fifty-three EAC resection specimens were immunostained with CD68, CD40 (M1), and CD163 (M2). Lymphatic vessel density (LVD) was estimated with the staining of D2-40. Subsequently, we tested if M2d macrophage could promote EAC cell migration and invasion. RESULTS: In EAC without neoadjuvant treatment, an increase in M2-like macrophage was associated with poor patient survival, independent of the locations of macrophages in tumour. The M2/M1 ratio that represented the balance between M2- and M1-like macrophages was significantly higher in nodal-positive EACs than that in nodal-negative EACs, and inversely correlated with patient overall survival. The M2/M1 ratio was not related to LVD. EAC cell polarised THP1 cell into M2d-like macrophage, which promoted EAC cell migration and invasion. Neoadjuvant therapy appeared to diminish the correlation between the M2/M1 ratio and survival. CONCLUSIONS: The ratio of M2/M1 macrophage may serve as a sensitive marker to predict lymph node metastasis and poor prognosis in EAC without neoadjuvant therapy. M2d macrophage may have important roles in EAC metastasis. PMID- 26263482 TI - The relationship between tumour budding, the tumour microenvironment and survival in patients with invasive ductal breast cancer. AB - BACKGROUND: Tumour budding has previously been reported to predict survival in several solid organ tumours, including breast; however, whether this is independent of other aspects of the tumour microenvironment is unknown. In the present study, the relationship between tumour budding, the tumour microenvironment and survival was examined in patients with invasive ductal breast cancer. METHODS: Patients presenting between 1995 and 1998 were studied (n=474). Using routine pathological sections, tumour budding was measured at the invasive margin and its association with clinicopathological characteristics and cancer-specific survival (CSS) was examined. RESULTS: Tumour budding was associated with several adverse pathological characteristics, including lymph node involvement, lymph vessel invasion (LVI), increased tumour stroma percentage (TSP) and weaker local inflammatory infiltrative. Tumour budding was associated with reduced CSS (hazard ratio (HR) 2.08, 95% confidence interval (CI) 1.14-3.09, P=0.004), independent of nodal status, molecular subtypes, tumour necrosis, CD8+, CD138+, LVI, blood vessel invasion and TSP. Further, tumour budding was independently associated with reduced CSS in node-negative patients (HR 2.63, 95% CI 1.16-5.92, P=0.020) and those who have low TSP (HR 1.98, 95% CI 1.09-3.57, P=0.024) and high-grade local inflammatory infiltrative (HR 2.27, 95% CI 1.35 5.36, P=0.014). CONCLUSIONS: Tumour budding was a significant predictor of survival in patients with invasive ductal breast cancer, independent of adverse pathological characteristics and components of tumour microenvironment. The present study further confirms the clinical utility of both tumour and host-based factors of tumour microenvironment. PMID- 26263484 TI - Heart-Rate Changes After an Ultraendurance Swim From Italy to Albania: A Case Report. AB - PURPOSE: To evaluate the effect of a solo ultraendurance open-water swim on autonomic and nonautonomic control of heart rate (HR). METHODS: A male athlete (age 48 y, height 172 cm, body mass 68 kg, BMI 23 kg/m2) underwent HR-variability (HRV) and circulating catecholamine evaluations at different times before and after an ultraendurance swim crossing the Adriatic Sea from Italy to Albania. HRV was measured in 5-min segments and quantified by time and frequency domain. Circulating catecholamines were estimated by salivary alpha-amylase (sAA) assay. RESULTS: The athlete completed 78.1 km in 23:44 h:min. After arrival, sAA levels had increased by 102.6%. Time- and frequency-domain HRV indexes decreased, as well (mean RR interval, -29,7%; standard deviation of normal mean RR interval, 63,1%; square root of mean squared successive differences between normal-to normal RR intervals, -49.3%; total power, -74.3%; low frequency, -78.0%; high frequency, -76.4%), while HR increased by 41.8%. At 16-h recovery, sAA had returned to preevent values, while a stable tachycardia was accompanied by reduced HRV measures. CONCLUSION: To the authors' knowledge, this is the first study reporting cardiac autonomic adjustments to an extreme and challenging ultraendurance open-water swim. The findings confirmed that the autonomic drives depend on exercise efforts. Since HRV changes did not mirror the catecholamine response 16 h postevent, the authors assume that the ultraendurance swim differently influenced cardiac function by both adaptive autonomic and nonautonomic patterns. PMID- 26263485 TI - Comparative biology of cell division in the fission yeast clade. AB - Cytokinesis must be regulated in time and space in order to preserve genome integrity during cell proliferation and to allow daughter cells to adopt distinct fates and geometries during differentiation. The fission yeast Schizosaccharomyces pombe has been a popular model organism for understanding spatiotemporal regulation of cytokinesis in a symmetrically dividing cell. Recent work on another member of the same genus, Schisozaccharomyces japonicus, suggests that S. pombe may have evolved an unusual division site placement mechanism based on a recently duplicated anillin paralog. Here we discuss an extraordinary evolutionary plasticity of cytokinesis within the fission yeast clade and argue that the comparative cell biology approach may provide functional insights beyond those afforded by scrutinizing individual model species. PMID- 26263483 TI - Fibulin-3 levels in malignant pleural mesothelioma are associated with prognosis but not diagnosis. AB - BACKGROUND: Fibulin-3 (FBLN3) was recently presented as a promising novel biomarker for malignant pleural mesothelioma (MPM), warranting independent validation studies. METHODS: ELISA was used to measure cellular and secreted FBLN3 in cell lines, in plasma of xenograft tumour-bearing mice, in plasma from two independent series of MPM and non-MPM patients and in pleural fluid from a third series. Diagnostic and prognostic potential of FBLN3 was assessed by receiver operating characteristics curve analysis and Kaplan-Meier method, respectively. RESULTS: FBLN3 was expressed in all MPM and benign mesothelial cell lines tested, and a correlation was observed between cellular protein expression and secreted levels. Human FBLN3 was detectable in plasma of tumour-bearing mice, suggesting that MPM cells contribute to levels of circulating FBLN3. Plasma FBLN3 was significantly elevated in MPM patients from the Sydney cohort, but not the Vienna cohort, but the diagnostic accuracy was low (63%, (95% CI: 50.1-76.4) and 56% (95% CI: 41.5-71.0), respectively). Although FBLN3 levels in pleural effusions were not significantly different between cases and controls, FBLN3 levels in pleural effusion fluid were found to be independently associated with prognosis (hazard ratio of 9.92 (95% CI: 2.14-45.93)). CONCLUSIONS: These data confirm the potential prognostic value of pleural effusion FBLN3, but question the diagnostic value of this protein in MPM patients. PMID- 26263486 TI - Effect of Cinnamon Oil on Quorum Sensing-Controlled Virulence Factors and Biofilm Formation in Pseudomonas aeruginosa. AB - Quorum sensing (QS) is a system of stimuli and responses in bacterial cells governed by their population density, through which they regulate genes that control virulence factors and biofilm formation. Despite considerable research on QS and the discovery of new antibiotics, QS-controlled biofilm formation by microorganisms in clinical settings has remained a problem because of nascent drug resistance, which requires screening of diverse compounds for anti-QS activities. Cinnamon is a dietary phytochemical that is traditionally used to remedy digestive problems and assorted contagions, which suggests that cinnamon might contain chemicals that can hinder the QS process. To test this hypothesis, the anti-QS activity of cinnamon oil against P. aeruginosa was tested, measured by the inhibition of biofilm formation and other QS-associated phenomena, including virulence factors such as pyocyanin, rhamnolipid, protease, alginate production, and swarming activity. To this end, multiple microscopy analyses, including light, scanning electron and confocal microscopy, revealed the ability of cinnamon oil to inhibit P. aeruginosa PAO1 biofilms and their accompanying extracellular polymeric substances. This work is the first to demonstrate that cinnamon oil can influence various QS-based phenomena in P. aeruginosa PAO1, including biofilm formation. PMID- 26263487 TI - The Novel Cyclophilin Inhibitor CPI-431-32 Concurrently Blocks HCV and HIV-1 Infections via a Similar Mechanism of Action. AB - HCV-related liver disease is the main cause of morbidity and mortality of HCV/HIV 1 co-infected patients. Despite the recent advent of anti-HCV direct acting antivirals (DAAs), the treatment of HCV/HIV-1 co-infected patients remains a challenge, as these patients are refractory to most therapies and develop liver fibrosis, cirrhosis and liver cancer more often than HCV mono-infected patients. Until the present study, there was no suitable in vitro assay to test the inhibitory activity of drugs on HCV/HIV-1 co-infection. Here we developed a novel in vitro "co-infection" model where HCV and HIV-1 concurrently replicate in their respective main host target cells--human hepatocytes and CD4+ T-lymphocytes. Using this co-culture model, we demonstrate that cyclophilin inhibitors (CypI), including a novel cyclosporin A (CsA) analog, CPI-431-32, simultaneously inhibits replication of both HCV and HIV-1 when added pre- and post-infection. In contrast, the HIV-1 protease inhibitor nelfinavir or the HCV NS5A inhibitor daclatasvir only blocks the replication of a single virus in the "co-infection" system. CPI-431-32 efficiently inhibits HCV and HIV-1 variants, which are normally resistant to DAAs. CPI-431-32 is slightly, but consistently more efficacious than the most advanced clinically tested CypI--alisporivir (ALV)--at interrupting an established HCV/HIV-1 co-infection. The superior antiviral efficacy of CPI-431-32 over ALV correlates with its higher potency inhibition of cyclophilin A (CypA) isomerase activity and at preventing HCV NS5A-CypA and HIV-1 capsid-CypA interactions known to be vital for replication of the respective viruses. Moreover, we obtained evidence that CPI-431-32 prevents the cloaking of both the HIV-1 and HCV genomes from cellular sensors. Based on these results, CPI 431-32 has the potential, as a single agent or in combination with DAAs, to inhibit both HCV and HIV-1 infections. PMID- 26263488 TI - Thermodynamic and fibril formation studies of full length immunoglobulin light chain AL-09 and its germline protein using scan rate dependent thermal unfolding. AB - Light chain (AL) amyloidosis is a fatal disease where monoclonal immunoglobulin light chains deposit as insoluble amyloid fibrils. For many years it has been considered that AL amyloid deposits are formed primarily by the variable domain, while its constant domain has been considered not to be amyloidogenic. However recent studies identify full length (FL) light chains as part of the amyloid deposits. In this report, we compare the stabilities and amyloidogenic properties of two light chains, an amyloid-associated protein AL-09 FL, and its germline protein kappa I O18/O8 FL (IGKV 1-33). We demonstrate that the thermal unfolding for both proteins is irreversible and scan rate dependent, with similar stability parameters compared to their VL counterparts. In addition, the constant domain seems to modulate their amyloidogenic properties and affect the morphology of the amyloid fibrils. These results allow us to understand the role of the kappa constant domain in AL amyloidosis. PMID- 26263489 TI - New Delhi Metallo-beta-Lactamase 1(NDM-1), the Dominant Carbapenemase Detected in Carbapenem-Resistant Enterobacter cloacae from Henan Province, China. AB - The emergence of New Delhi metallo-beta-lactamase 1 (NDM-1) has become established as a major public health threat and represents a new challenge in the treatment of infectious diseases. In this study, we report a high incidence and endemic spread of NDM-1-producing carbapenem-resistant Enterobacter cloacae isolates in Henan province, China. Eight (72.7%) out of eleven non-duplicated carbapenem-resistant E. cloacae isolates collected between June 2011 and May 2013 were identified as NDM-1 positive. The blaNDM-1 gene surrounded by an entire ISAba125 element and a bleomycin resistance gene bleMBL in these isolates were carried by diverse conjugatable plasmids (IncA/C, IncN, IncHI2 and untypeable) ranging from ~55 to ~360 kb. Molecular epidemiology analysis revealed that three NDM-1-producing E. cloacae belonged to the same multilocus sequence type (ST), ST120, two of which were classified as extensively drug-resistant (XDR) isolates susceptible only to tigecycline and colistin. The two XDR ST120 E. cloacae isolates co-harbored blaNDM-1, armA and fosA3 genes and could transfer resistance to carbapenems, fosfomycin and aminoglycosides simultaneously via a conjugation experiment. Our study demonstrated NDM-1 was the most prevalent metallo-beta lactamase (MBL) among carbapenem-resistant E.cloacae isolates and identified a potential endemic clone of ST120 in Henan province. These findings highlight the need for enhanced efforts to monitor the further spread of NDM-1 and XDR ST120 E. cloacae in this region. PMID- 26263490 TI - Relative Brain and Brain Part Sizes Provide Only Limited Evidence that Machiavellian Behaviour in Cleaner Wrasse Is Cognitively Demanding. AB - It is currently widely accepted that the complexity of a species' social life is a major determinant of its brain complexity, as predicted by the social brain hypothesis. However, it remains a challenge to explain what social complexity exactly is and what the best corresponding measures of brain anatomy are. Absolute and relative size of the brain and of the neocortex have often been used as a proxy to predict cognitive performance. Here, we apply the logic of the social brain hypothesis to marine cleaning mutualism involving the genus Labroides. These wrasses remove ectoparasites from 'client' reef fish. Conflict occurs as wrasse prefer client mucus over ectoparasites, where mucus feeding constitutes cheating. As a result of this conflict, cleaner wrasse show remarkable Machiavellian-like behaviour. Using own data as well as available data from the literature, we investigated whether the general brain anatomy of Labroides provides any indication that their Machiavellian behaviour is associated with a more complex brain. Neither data set provided evidence for an increased encephalisation index compared to other wrasse species. Published data on relative sizes of brain parts in 25 species of the order Perciformes suggests that only the diencephalon is relatively enlarged in Labroides dimidiatus. This part contains various nuclei of the social decision making network. In conclusion, gross brain anatomy yields little evidence for the hypothesis that strategic behaviour in cleaning selects for larger brains, while future research should focus on more detailed aspects like the sizes of specific nuclei as well as their cryoarchitectonic structure and connectivity. PMID- 26263491 TI - Adenosine Receptors Differentially Regulate the Expression of Regulators of G Protein Signalling (RGS) 2, 3 and 4 in Astrocyte-Like Cells. AB - The "regulators of g-protein signalling" (RGS) comprise a large family of proteins that limit by virtue of their GTPase accelerating protein domain the signal transduction of G-protein coupled receptors. RGS proteins have been implicated in various neuropsychiatric diseases such as schizophrenia, drug abuse, depression and anxiety and aggressive behaviour. Since conditions associated with a large increase of adenosine in the brain such as seizures or ischemia were reported to modify the expression of some RGS proteins we hypothesized that adenosine might regulate RGS expression in neural cells. We measured the expression of RGS-2,-3, and -4 in both transformed glia cells (human U373 MG astrocytoma cells) and in primary rat astrocyte cultures stimulated with adenosine agonists. Expression of RGS-2 mRNA as well as RGS2 protein was increased up to 30-fold by adenosine agonists in astrocytes. The order of potency of agonists and the blockade by the adenosine A2B-antagonist MRS1706 indicated that this effect was largely mediated by adenosine A2B receptors. However, a smaller effect was observed due to activation of adenosine A2A receptors. In astrocytoma cells adenosine agonists elicited an increase in RGS-2 expression solely mediated by A2B receptors. Expression of RGS-3 was inhibited by adenosine agonists in both astrocytoma cells and astrocytes. However while this effect was mediated by A2B receptors in astrocytoma cells it was mediated by A2A receptors in astrocytes as assessed by the order of potency of agonists and selective blockade by the specific antagonists MRS1706 and ZM241385 respectively. RGS-4 expression was inhibited in astrocytoma cells but enhanced in astrocytes by adenosine agonists. PMID- 26263492 TI - Composite films of polydopamine-Alcian Blue for colored coating with new physical properties. AB - Polydopamine (PDA) coatings appear as a universal functionalization methodology allowing to coat the surface of almost all kinds of known materials with a conformal, stable, robust and reactive material. Relatively few investigations were dedicated to the incorporation of other molecules in PDA coatings during their deposition from dopamine solutions under oxidative conditions. Herein we rely on the assumption that the basic building blocks of PDA could be porphyrin like tetramers (as well as higher order oligomers) of 5,6-dihydroxyindole and we investigate the influence of a cationic Cu(II) phtalocyanine, namely Alcian Blue (AB), on the deposition kinetics and on the properties of PDA films. We demonstrate that AB is indeed incorporated in the PDA films to yield a composite PDA-AB coating displaying the optical features of both PDA and AB. The amount of incorporated dye depends on its concentration in solution. The obtained PDA-AB films have a smaller thickness than their related PDA counterparts, a different morphology and a higher permeability to the anionic hexacyanoferrate redox probe. In addition, the incorporation of AB in the films is not homogeneous through their thickness as inferred by means of X-ray photoelectron spectroscopy. The reason for this interesting finding is discussed on the basis of the interactions between AB and PDA as well as on the basis of the structure of PDA films. PMID- 26263493 TI - Effect of lipophilization on the distribution and reactivity of ingredients in emulsions. AB - HYPOTHESIS: The reactivity of small molecules in emulsions is believed to depend on their partitioning between phases, yet this is hard to verify experimentally in situ. In the present work, we use electron paramagnetic resonance (EPR) spectroscopy to simultaneously measure the distribution and reactivity of a homologous series of lipophilized spin probes in an emulsion. EXPERIMENTS: 4 Hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPOL) was derivatized with saturated fatty acids to create a series of spin probes with increasing lipophilicity (C4-, C8-, C12-, and C16-TEMPO). The probes were added to a 10 wt.% tetradecane-in water emulsions (d32~190 nm) stabilized with sodium caseinate (1 wt.% in the aqueous phase, pH 7). The distribution of the probes between phases was measured by electron paramagnetic resonance (EPR) spectroscopy. FINDINGS: TEMPOL partitioned into the aqueous phase, C4-TEMPO distributed between the lipid and aqueous phases (69% and 31% respectively) while the more lipophilic probes dissolved exclusively within the lipid droplets. Interestingly, the more lipophilic probes initially precipitated upon their addition to the emulsion, and only slowly redistributed to the droplets over hours or days, the rate of which was dependent on their carbon chain length. The reactivity of the probes with aqueous an aqueous phase reductant (ascorbate) generally depended on the proportion in the aqueous phase (i.e., TEMPOL>C4-TEMPO>C8-TEMPO~C12-TEMPO~C16 TEMPO). PMID- 26263494 TI - Enhanced fluorescence and heat dissipation of calcium titanate red phosphor based on silver coating. AB - Phosphor plays an important role in LEDs-the next generation of lighting source. However, many families of phosphor like titanate still face two severe problems: Low photoluminescence (PL) efficiency and poor thermal stability. Herein, the silver coating is applied to alleviate the above challenges. Ag nanoparticles with different morphology like disks or triangular plates are synthesised by a simple sol-reduction method, and then coated on the shape-regular CaTiO3:Eu (CTOE) phosphor. When the localized surface plasmon resonance (LSPR) extinction spectrum of Ag nanoparticles matches well with excitation or emission wavelength, the PL intensity of CTOE phosphor would be efficiently enhanced. There is an optimum point of LSPR coating amount due to the balance of LSPR-enhancement and scattering/reflection-reduction of Ag nanoparticles. The coating of Ag also leads to an improvement in heat dissipation of CTOE phosphors; meanwhile an overmuch of Ag would also reduce the luminous efficiency. Thus the most suitable coating amount based on the overall consideration successfully enables the enhancement of both PL intensity and heat dissipation, and the pc-LED lamp packaged with Ag coated CTOE phosphor also shows a higher efficiency and more stable working status than the uncoated ones. PMID- 26263495 TI - Direct observation by using Brewster angle microscopy of the diacetylene polimerization in mixed Langmuir film. AB - Mixed Langmuir monolayers of 10,12-Pentacosadiynoic acid (DA) and amphiphilic hemicyanine (HSP) have been fabricated at the air-water interface. The mixed monolayer has been proved to be completely homogeneous. The DA molecules are arranged in a single monolayer within the mixed Langmuir monolayer, as opposed to the typical trilayer architecture for the pure DA film. Brewster angle microscopy has been used to reveal the mesoscopic structure of the mixed Langmuir monolayer. Flower shape domains with internal anisotropy due the ordered alignment of hemicyanine groups have been observed. Given the absorption features of the hemicyanine groups at the wavelength used in the BAM experiments, the enhancement of reflection provoked by the absorption process leads to the observed anisotropy. The ordering of such groups is promoted by their strong self aggregation tendency. Under UV irradiation at the air-water interface, polydiacetylene (PDA) has been fabricated. In spite a significant increase in the domains reflectivity has been observed owing to the modification in the mentioned enhanced reflection, the texture of the domains remains equal. The PDA polymer chain therefore grows in the same direction in which the HSP molecules are aligned. This study is expected to enrich the understanding and design of fabrication of PDA at interfaces. PMID- 26263496 TI - Self-limiting adsorption of Eu3+ on the surface of rod-shape anatase TiO2 nanocrystals and post-synthetic sensitization of the europium-based emission. AB - The surface of oleic acid stabilized rod-shape anatase TiO2 nanocrystals was modified by adsorption of Eu(3+) ions. The Eu(3+) attachment showed Langmuir adsorption behavior, thus the loading of Eu(3+) could be controlled precisely up to surface saturation coverage. The Eu(3+)-TiO2 nanorods show weak Eu(3+) based luminescence. However, addition of thenoyltrifluoroacetone (TTFA) leads to coordination of the ligand to the Eu(3+) centers and the TTFA-Eu(3+)-TiO2 materials exhibit strong Eu(3+) fluorescence sensitized by the TTFA ligand. PMID- 26263497 TI - Olive oil and hyperthermal water bigels for cosmetic uses. AB - Bigels are biphasic systems produced with an organogel (or oleogel) and a hydrogel mixed together at high shear rates. These systems are promising for different uses, among them the formulation of new cosmetic matrices for cosmetic agents delivery is under investigation. In the present paper, a common cosmetic formulation for skin care was enriched with increasing fractions of monoglycerides of fatty acids/olive oil organogels, in order to understand the rheology and the microstructure of these systems. Small amplitude oscillation tests, NMR-self diffusion analysis, contrast phase microscopy and electric conductivity confirmed that the addition of the organogel caused a microstructural change of the starting material, which turned from O/W to a more complex system where, probably, a matrix-in-matrix structure is present at the highest fractions of added organogel. PMID- 26263498 TI - Facile synthesis of magnetically separable reduced graphene oxide/magnetite/silver nanocomposites with enhanced catalytic activity. AB - In this study, the combination of magnetite (Fe3O4) with reduced graphene oxide (RGO) generates a new hybrid substrate for the dispersion of noble metal nanoparticles. Well-dispersed silver (Ag) nanoparticles loaded on the surface of Fe3O4 modified RGO are achieved by an efficient two-step approach. Through reducing Ag(+) ions, highly dispersed Ag nanoparticles are in-situ formed on the RGO/Fe3O4 substrate. It is found that the existence of Fe3O4 nanocrystals can significantly improve the dispersity and decrease the particle size of the in situ formed Ag nanoparticles. Magnetic study reveals that the as-prepared RGO/Fe3O4/Ag ternary nanocomposites display room-temperature superparamagnetic behavior. The catalytic properties of the RGO/Fe3O4/Ag ternary nanocomposites were evaluated with the reduction of 4-nitrophenol into 4-aminophenol as a model reaction. The as-synthesized RGO/Fe3O4/Ag ternary catalysts exhibit excellent catalytic stability and much higher catalytic activity than the corresponding RGO/Ag catalyst. Moreover, the RGO/Fe3O4/Ag catalysts can be easily magnetically separated for reuse. This study further demonstrates that nanoparticles modified graphene can act as an effective hybrid substrate for the synthesis of multi component and multifunctional graphene-based composites. PMID- 26263499 TI - Conducting polymer-gold co-patterned surfaces via nanosphere lithography. AB - HYPOTHESIS: Co-patterned arrays comprised of conjugated polymers and nanostructured gold is an important matrix for sensing and stimuli-responsive plasmonic applications. Nanosphere lithography (NSL) is an easy-to-use patterning technique and viable method to fabricate inverse honeycomb structures with electrochemically deposited conjugated polymers. The cross-sectional height of the conducting polymer pattern can be tuned such that the macropores of the honeycomb structure expose electrochemically accessible areas for further gold deposition. Using time-dependent electrochemical reduction, Au(3+) is reduced to Au(0) and selectively deposit on the macropores thus forming a co-patterned surface. EXPERIMENTS: The Langmuir-Blodgett-like deposition was used to assemble polystyrene spheres on a conductive substrate. Then the carbazole-based monomer was electropolymerized within the interstices of the colloidal template, which was subsequently dissolved. A potentiostatic technique was used to deposit Au in the macropores. FINDINGS: Fabrication of the polycarbazole-Au co-patterned surface was characterized by atomic force microscopy (AFM), electrochemical quartz crystal microbalance (EC-QCM), and X-ray photoelectron spectroscopy (XPS). Surface plasmon resonance spectroscopy (SPS) data supported backfilling behavior and quantified the complex refractive index of the array. UV-Vis absorption spectroscopy shows overlapping polycarbazole and gold LSPR peaks useful for plasmonic sensing applications. The colloidal templating approach reported in this study was further used in the fabrication of highly ordered Au nanodisks. PMID- 26263500 TI - The viral context instructs the redundancy of costimulatory pathways in driving CD8(+) T cell expansion. AB - Signals delivered by costimulatory molecules are implicated in driving T cell expansion. The requirements for these signals, however, vary from dispensable to essential in different infections. We examined the underlying mechanisms of this differential T cell costimulation dependence and found that the viral context determined the dependence on CD28/B7-mediated costimulation for expansion of naive and memory CD8(+) T cells, indicating that the requirement for costimulatory signals is not imprinted. Notably, related to the high-level costimulatory molecule expression induced by lymphocytic choriomeningitis virus (LCMV), CD28/B7-mediated costimulation was dispensable for accumulation of LCMV specific CD8(+) T cells because of redundancy with the costimulatory pathways induced by TNF receptor family members (i.e., CD27, OX40, and 4-1BB). Type I IFN signaling in viral-specific CD8(+) T cells is slightly redundant with costimulatory signals. These results highlight that pathogen-specific conditions differentially and uniquely dictate the utilization of costimulatory pathways allowing shaping of effector and memory antigen-specific CD8(+) T cell responses. PMID- 26263502 TI - Greater functional improvement in patients with diabetes after rehabilitation following cardiac surgery. AB - BACKGROUND: Diabetes increases the risk of in-hospital complications in medical or surgical patients. Few data are available in the rehabilitation phase after cardiac surgery. AIM: To assess the influence of diabetes on outcome and complication rate in the rehabilitation phase after cardiac surgery. METHODS: Data prospectively recorded in the Hospital Information System from 5261 patients consecutively admitted between 1 January 2008 and 31 May 2013 for a comprehensive cardiac rehabilitation programme directly after cardiac surgery were analysed retrospectively. RESULTS: The study cohort included 1285 (24%) patients with diabetes and 3976 (76%) without. Coronary artery bypass graft (CABG) was more frequent in patients with diabetes (58% vs. 37%, P < 0.01), and valvular surgery was more frequent in patients without diabetes (37% vs. 22%, P < 0.01). Patients with diabetes were more disabled after surgery, with severe disability (Barthel Index < 60) observed in 22% (vs. 17% in patients without diabetes, P < 0.001). During rehabilitation, complications were more frequent in patients with diabetes than those without (28% vs. 21%, P < 0.01); in particular, patients with diabetes had more infections, heart failure and more difficult surgical wound healing. However, the improvement in the Barthel Index was greater in patients with diabetes (+16 +/- 15) than without (+13 +/- 15, P < 0.001). CONCLUSIONS: In a large cohort of patients directly admitted to an early inpatient rehabilitation programme after cardiac surgery, those with diabetes were more disabled. Nonetheless, and despite the higher rate of complications, patients with diabetes had the greatest benefit in terms of functional improvement. PMID- 26263501 TI - SnRK1-triggered switch of bZIP63 dimerization mediates the low-energy response in plants. AB - Metabolic adjustment to changing environmental conditions, particularly balancing of growth and defense responses, is crucial for all organisms to survive. The evolutionary conserved AMPK/Snf1/SnRK1 kinases are well-known metabolic master regulators in the low-energy response in animals, yeast and plants. They act at two different levels: by modulating the activity of key metabolic enzymes, and by massive transcriptional reprogramming. While the first part is well established, the latter function is only partially understood in animals and not at all in plants. Here we identified the Arabidopsis transcription factor bZIP63 as key regulator of the starvation response and direct target of the SnRK1 kinase. Phosphorylation of bZIP63 by SnRK1 changed its dimerization preference, thereby affecting target gene expression and ultimately primary metabolism. A bzip63 knock-out mutant exhibited starvation-related phenotypes, which could be functionally complemented by wild type bZIP63, but not by a version harboring point mutations in the identified SnRK1 target sites. PMID- 26263503 TI - Ni-Catalyzed Synthesis of Fluoroarenes via [2+2+2] Cycloaddition Involving alpha Fluorine Elimination. AB - A method for direct synthesis of tetrasubstituted fluoroarenes via nickel catalyzed [2+2+2] cycloaddition is presented. The reaction combines one molecule of 1,1-difluoroethylene with two molecules of alkynes and involves sequential cleavage of the C-F and C-H bonds in difluoroethylene. The catalytic cycle is established by reduction of the intermediary Ni(II) fluoride with a triethylborane-based borate. PMID- 26263504 TI - Prognostic Value of Yes-Associated Protein 1 (YAP1) in Various Cancers: A Meta Analysis. AB - BACKGROUND: Yes-associated protein 1 (YAP1) is an effector of Hippo pathway, which is critical for regulating organ size, cell proliferation and tumor growth in mammals. Many previous studies have explored the relationship between YAP1 and various types of cancer. However, these studies were limited by the small samples size and the findings were inconsistent among them. Therefore, a meta-analysis was conducted to assess the association between YAP1 and malignancies. METHODS: A systematic literature search was conducted for eligible studies in the PubMed, Corchane Library, Web of Knowledge, EMBASE and CBM disc databases from inception to August 1st 2014. After heterogeneity analysis, pooled harzad ratio (HR) with 95% confidence interval (95%CI) using both fixed and random effect models were estimated in STATA 10.0. Meta regression analysis, subgroup analysis and sensitivity analysis were performed to explore the potential sources of heterogeneity and to evaluate the robustness of the result. Publication bias was assessed by Egger's test and funnel plot. RESULTS: A total of 21 unique articles from 2009 to 2014, comprising 2983 patients, were analyzed in the meta-analysis. The association of YAP1 expression and overall survival time (OS) was evaluated in 20 studies including 2067 patients. Positive YAP1 showed poorer OS (HR = 1.826; 95% CI = 1.465-2.275; p <0.002). For evaluating disease-free survival time (DFS), 10 studies with 1139 patients were analyzed. Positive YAP1 indicated worse DFS (HR = 2.114; 95%CI = 1.406-3.179; p <0.001). Subgroup analysis showed that both positive nuclear YAP1 (HR = 1.390, 95% CI: 0.810-2.400, p = 0.729) and up regulation overall YAP1 (HR = 2.237, 95% CI: 1.548-3.232, p <0.001) had poorer OS for patients with malignancies. Similarly, both positive nuclear YAP1 (HR = 3.733, 95% CI: 1.469-9.483, p = 0.001) and up-regulation overall YAP1 (HR = 1.481, 95% CI: 1.163-1.886, p = 0.554) showed worse DFS. The patients with urogenital system cancer had the poorest OS (HR = 2.133, 95% CI: 1.549-2.937, p = 0.020). The patients with alimentary system cancer had the most significant impact on DFS (HR = 1.879, 95% CI: 1.537-2.297, p <0.001). CONCLUSION: Both overall and nuclear YAP1 overexpression are intimately associated with adverse OS and DFS in numerous cancers, suggesting that YAP1 may act as a potential therapeutic targets of these malignancies in the future. PMID- 26263505 TI - MEP Latencies Predict the Neuromodulatory Effect of cTBS Delivered to the Ipsilateral and Contralateral Sensorimotor Cortex. AB - BACKGROUND: Recently, it was shown that the highly variable after-effect of continuous theta-burst stimulation (cTBS) of the primary motor cortex (M1) can be predicted by the latency of motor-evoked potentials (MEPs) recorded before cTBS. This suggests that at least part of this inter-individual variability is driven by differences in the neuronal populations preferentially activated by transcranial magnetic stimulation (TMS). METHODS: Here, we recorded MEPs, TMS evoked brain potentials (TEPs) and somatosensory-evoked potentials (SEPs) to investigate the effects of cTBS delivered over the primary sensorimotor cortex on both the ipsilateral and contralateral M1, and the ipsilateral and contralateral primary somatosensory cortex (S1). RESULTS: We confirm that the after-effects of cTBS can be predicted by the latency of MEPs recorded before cTBS. Over the hemisphere onto which cTBS was delivered, short-latency MEPs at baseline were associated with an increase of MEP magnitude (i.e. an excitatory effect of cTBS) whereas late-latency MEPs were associated with reduced MEPs (i.e. an inhibitory effect of cTBS). This relationship was reversed over the contralateral hemisphere, indicating opposite effects of cTBS on the responsiveness of the ipsilateral and contralateral M1. Baseline MEP latencies also predicted changes in the magnitude of the N100 wave of TEPs elicited by stimulation of the ipsilateral and contralateral hemisphere, indicating that this TEP component is specifically dependent on the state of M1. Finally, there was a reverse relationship between MEP latency and the effects of cTBS on the SEP waveforms (50 130 ms), indicating that after-effects of cTBS on S1 are opposite to those on M1. CONCLUSION: Taken together, our results confirm that the variable after-effects of cTBS can be explained by differences in the neuronal populations activated by TMS. Furthermore, our results show that this variability also determines remote effects of cTBS in S1 and the contralateral hemisphere, compatible with inter hemispheric and sensorimotor interactions. PMID- 26263506 TI - Effect of Support on the Activity of Ag-based Catalysts for Formaldehyde Oxidation. AB - Ag-based catalysts with different supports (TiO2, Al2O3 and CeO2) were prepared by impregnation method and subsequently tested for the catalytic oxidation of formaldehyde (HCHO) at low temperature. The Ag/TiO2 catalyst showed the distinctive catalytic performance, achieving the complete HCHO conversion at around 95 degrees C. In contrast, the Ag/Al2O3 and Ag/CeO2 catalysts displayed much lower activity and the 100% conversion was reached at 110 degrees C and higher than 125 degrees C, respectively. The Ag-based catalysts were next characterized by several methods. The characterization results revealed that supports have the dramatic influence on the Ag particle sizes and dispersion. Kinetic tests showed that the Ag based catalyst on the TiO2, Al2O3 or CeO2 supports have the similar apparent activation energy of 65 kJ mol(-1), indicating that the catalytic mechanism keep immutability over these three catalysts. Therefore, Ag particle size and dispersion was confirmed to be the main factor affecting the catalytic performance for HCHO oxidation. The Ag/TiO2 catalyst has the highest Ag dispersion and the smallest Ag particle size, accordingly presenting the best catalytic performance for HCHO oxidation. PMID- 26263507 TI - Reduction of Solar UV Radiation Due to Urban High-Rise Buildings--A Coupled Modelling Study. AB - Solar UV radiation has both adverse and beneficial effects to human health. Using models (a radiative transfer model coupled to a building shading model), together with satellite and surface measurements, we studied the un-obstructed and obstructed UV environments in a sub-tropical urban environment featured with relatively high pollution (aerosol) loadings and high-rise buildings. Seasonal patterns of the erythemal UV exposure rates were governed by solar zenith angles, seasonal variations of aerosol loadings and cloud effects. The radiative transfer modelling results agreed with measurements of erythemal UV exposure rates and spectral irradiances in UVA and UVB ranges. High-rise buildings and narrow road width (height to width, H/W, ratios up to 15) reduced the modelled total UV (UVA+UVB) radiation and leave 10% of the un-obstructed exposure rate at ground level at noon. No more than 80% of the un-obstructed exposure rate was received in the open area surrounded by 20-storey buildings. Our modelled reduction of UVB radiation in the urban environment was consistent with similar measurements obtained for Australia. However, our results in more extreme environments (higher H/W ratios) were for the first time reported, with 18% of the un-obstructed exposure rate remained at the ground-level center of the street canyon. PMID- 26263508 TI - Bacteria-zinc co-localization implicates enhanced synthesis of cysteine-rich peptides in zinc detoxification when Brassica juncea is inoculated with Rhizobium leguminosarum. AB - Some plant growth promoting bacteria (PGPB) are enigmatic in enhancing plant growth in the face of increased metal accumulation in plants. Since most PGPB colonize the plant root epidermis, we hypothesized that PGPB confer tolerance to metals through changes in speciation at the root epidermis. We employed a novel combination of fluorophore-based confocal laser scanning microscopic imaging and synchrotron based microscopic X-ray fluorescence mapping with X-ray absorption spectroscopy to characterize bacterial localization, zinc (Zn) distribution and speciation in the roots of Brassica juncea grown in Zn contaminated media (400 mg kg(-1) Zn) with the endophytic Pseudomonas brassicacearum and rhizospheric Rhizobium leguminosarum. PGPB enhanced epidermal Zn sequestration relative to PGBP-free controls while the extent of endophytic accumulation depended on the colonization mode of each PGBP. Increased root accumulation of Zn and increased tolerance to Zn was associated predominantly with R. leguminosarum and was likely due to the coordination of Zn with cysteine-rich peptides in the root endodermis, suggesting enhanced synthesis of phytochelatins or glutathione. Our mechanistic model of enhanced Zn accumulation and detoxification in plants inoculated with R. leguminosarum has particular relevance to PGPB enhanced phytoremediation of soils contaminated through mining and oxidation of sulphur-bearing Zn minerals or engineered nanomaterials such as ZnS. PMID- 26263509 TI - The Immunoreactive Exo-1,3-beta-Glucanase from the Pathogenic Oomycete Pythium insidiosum Is Temperature Regulated and Exhibits Glycoside Hydrolase Activity. AB - The oomycete organism, Pythium insidiosum, is the etiologic agent of the life threatening infectious disease called "pythiosis". Diagnosis and treatment of pythiosis is difficult and challenging. Novel methods for early diagnosis and effective treatment are urgently needed. Recently, we reported a 74-kDa immunodominant protein of P. insidiosum, which could be a diagnostic target, vaccine candidate, and virulence factor. The protein was identified as a putative exo-1,3-beta-glucanase (Exo1). This study reports on genetic, immunological, and biochemical characteristics of Exo1. The full-length exo1 coding sequence (2,229 bases) was cloned. Phylogenetic analysis showed that exo1 is grouped with glucanase-encoding genes of other oomycetes, and is far different from glucanase encoding genes of fungi. exo1 was up-regulated upon exposure to body temperature, and its gene product is predicted to contain BglC and X8 domains, which are involved in carbohydrate transport, binding, and metabolism. Based on its sequence, Exo1 belongs to the Glycoside Hydrolase family 5 (GH5). Exo1, expressed in E. coli, exhibited beta-glucanase and cellulase activities. Exo1 is a major intracellular immunoreactive protein that can trigger host immune responses during infection. Since GH5 enzyme-encoding genes are not present in human genomes, Exo1 could be a useful target for drug and vaccine development against this pathogen. PMID- 26263510 TI - Depth-Dependent Mineral Soil CO2 Production Processes: Sensitivity to Harvesting Induced Changes in Soil Climate. AB - Forest harvesting induces a step change in the climatic variables (temperature and moisture), that control carbon dioxide (CO2) production arising from soil organic matter decomposition within soils. Efforts to examine these vertically complex relationships in situ within soil profiles are lacking. In this study we examined how the climatic controls on CO2 production change within vertically distinct layers of the soil profile in intact and clearcut forest soils of a humid temperate forest system of Atlantic Canada. We measured mineral soil temperature (0, 5, 10, 20, 50 and 100 cm depth) and moisture (0-15 cm and 30-60 cm depth), along with CO2 surface efflux and subsurface concentrations (0, 2.5, 5, 10, 20, 35, 50, 75 and 100 cm depth) in 1 m deep soil pits at 4 sites represented by two forest-clearcut pairs over a complete annual cycle. We examined relationships between surface efflux at each site, and soil heat, moisture, and mineral soil CO2 production. Following clearcut harvesting we observed increases in temperature through depth (1-2 degrees C annually; often in excess of 4 degrees C in summer and spring), alongside increases in soil moisture (30%). We observed a systematic breakdown in the expected exponential relationship between CO2 production and heat with mineral soil depth, consistent with an increase in the role moisture plays in constraining CO2 production. These findings should be considered in efforts to model and characterize mineral soil organic matter decomposition in harvested forest soils. PMID- 26263511 TI - The A Allele at rs13419896 of EPAS1 Is Associated with Enhanced Expression and Poor Prognosis for Non-Small Cell Lung Cancer. AB - Hypoxia-inducible factor-2alpha (HIF-2alpha, or EPAS1) is important for cancer progression, and is a putative biomarker for poor prognosis for non-small cell lung cancer (NSCLC). However, molecular mechanisms underlying the EPAS1 overexpression are not still fully understood. We explored a role of a single nucleotide polymorphism (SNP), rs13419896 located within intron 1 of the EPAS1 gene in regulation of its expression. Bioinformatic analyses suggested that a region including the rs13419896 SNP plays a role in regulation of the EPAS1 gene expression and the SNP alters the binding activity of transcription factors. In vitro analyses demonstrated that a fragment containing the SNP locus function as a regulatory region and that a fragment with A allele showed higher transactivation activity than one with G, especially in the presence of overexpressed c-Fos or c-Jun. Moreover, NSCLC patients with the A allele showed poorer prognosis than those with G at the SNP even after adjustment with various variables. In conclusion, the genetic polymorphism of the EPAS1 gene may lead to variation of its gene expression levels to drive progression of the cancer and serve as a prognostic marker for NSCLC. PMID- 26263512 TI - Genomic Analysis and Isolation of RNA Polymerase II Dependent Promoters from Spodoptera frugiperda. AB - The Baculoviral Expression Vector System (BEVS) is the most commonly used method for high expression of recombinant protein in insect cells. Nevertheless, expression of some target proteins--especially those entering the secretory pathway--provides a severe challenge for the baculovirus infected insect cells, due to the reorganisation of intracellular compounds upon viral infection. Therefore, alternative strategies for recombinant protein production in insect cells like transient plasmid-based expression or stable expression cell lines are becoming more popular. However, the major bottleneck of these systems is the lack of strong endogenous polymerase II dependent promoters, as the strong baculoviral p10 and polH promoters used in BEVS are only functional in presence of the viral transcription machinery during the late phase of infection. In this work we present a draft genome and a transcriptome analysis of Sf21 cells for the identification of the first known endogenous Spodoptera frugiperda promoters. Therefore, putative promoter sequences were identified and selected because of high mRNA level or in analogy to other strong promoters in other eukaryotic organism. The chosen endogenous Sf21 promoters were compared to early viral promoters for their efficiency to trigger eGFP expression using transient plasmid based transfection in a BioLector Microfermentation system. Furthermore, promoter activity was not only shown in Sf21 cells but also in Hi5 cells. The novel endogenous Sf21 promoters were ranked according to their activity and expand the small pool of available promoters for stable insect cell line development and transient plasmid expression in insect cells. The best promoter was used to improve plasmid based transient transfection in insect cells substantially. PMID- 26263514 TI - HLA B51 is associated with faster AIDS progression among newly diagnosed HIV infected individuals in Manitoba, Canada. AB - Human leucocyte antigen (HLA) alleles influence the rate of CD4 decline among HIV infected individuals. We investigated the association between HLA B35 and HLA B51 and the rate of CD4 decline and/or opportunistic infections, among 294 HIV positive individuals from Manitoba, Canada. All individuals presenting with a CD4 count >200 cells MUL(-1) , who had at least two CD4 counts, and no evidence of co infection were included. Individuals bearing HLA B35 or HLA B51 were compared to controls. A multivariate model demonstrated that HLA B35 allele was associated with a hazard ratio of 2.05 (95% CI 1.31-3.18) for reaching AIDS and HLA B51 allele with HR of 2.03 (95% CI 1.18-3.49) for reaching the same end-point. High prevalence of HLA B35 was seen in the patient population receiving care in Manitoba. Our observations confirm the association of HLA B35 with rapid disease progression. We report, for the first time, faster CD4 decline among individuals with HLA B51 allele. PMID- 26263513 TI - Mechanism of NHC-Catalyzed Conjugate Additions of Diboron and Borosilane Reagents to alpha,beta-Unsaturated Carbonyl Compounds. AB - Broadly applicable enantioselective C-B and C-Si bond-forming processes catalyzed by an N-heterocyclic carbene (NHC) were recently introduced; these boryl and silyl conjugate addition reactions (BCA and SCA, respectively), which proceed without the need for a transition-metal complex, represent reaction pathways that are distinct from those facilitated by transition-metal-containing species (e.g., Cu, Ni, Pt, Pd, or Rh based). The Lewis-base-catalyzed (NHC) transformations are valuable to chemical synthesis, as they can generate high enantioselectivities and possess unique chemoselectivity profiles. Here, the results of investigations that elucidate the principal features of the NHC-catalyzed BCA and SCA processes are detailed. Spectroscopic evidence is provided illustrating why the presence of excess base and MeOH or H2O is required for efficient and enantioselective boryl and silyl addition reactions. It is demonstrated that the proton sources influence the efficiency and/or enantioselectivity of NHC-catalyzed enantioselective transformations in several ways. The positive, and at times adverse, impact of water (biphasic conditions) on catalytic enantioselective silyl addition reactions is analyzed. It is shown that a proton source can facilitate nonenantioselective background reactions and NHC decomposition, requiring the catalyst to surpass such complications. Stereochemical models are presented that account for the identity of the observed major enantiomers, providing a rationale for the differences in selectivity profiles of BCA and SCA processes. PMID- 26263515 TI - Ultraviolet-B radiation applied to detached peach fruit: A study of free radical generation by EPR spin trapping. AB - In peaches, phenolic compounds are the major sources of antioxidants, and cyanidin-3-O-glucoside is the main anthocyanin present, above all in the skin. Anthocyanin content has been shown to increase after UV-B irradiation, which may be very harmful for all biological organisms due to the induction of the generation of reactive oxygen species (ROS). Peach fruits (cv. 'Suncrest') were exposed during post-harvest to supplemental ultraviolet-B radiation. A spin trapping technique was used to monitor the generation of free radicals under UV B, and 5-(diethoxy-phosphoryl)-5-methyl-1-pyrroline-N-oxide (DEPMPO) was used as the spin trap. The flesh of peaches was essentially unaffected by the treatment, whereas the skin was responsive at the end of the treatment, accumulating ascorbate, flavonoids, cyanidin-3-O-glucoside, and showing a higher antioxidant activity. The levels of stable free radicals were also lower at the end of treatment. Carbon-centred radicals contributed the most to the total amounts of free radicals, whereas hydroxyl radicals and oxygen-centred free radicals contributed minimally. The carbon-centred free radical identified was the same as the one obtained after irradiation of authentic cyanidin-3-O-glucoside. During UV B treatment cyanidin-3-O-glucoside increased and was capable of radicalization protecting the other organic molecules of the cell from oxidation. ROS, among which hydroxyl radicals, were thus maintained to minimal levels. This ability of cyanidin-3-O-glucoside displayed the mechanism underlined the tolerance to UV-B irradiation indicating that shelf life can be prolonged by the presence of anthocyanins. Thus, UV-B technique results a good approach to induce antioxidant production in peach fruits increasing their nutraceutical properties. PMID- 26263516 TI - Stress-responsive expression patterns and functional characterization of cold shock domain proteins in cabbage (Brassica rapa) under abiotic stress conditions. AB - Although the functional roles of cold shock domain proteins (CSDPs) have been demonstrated during the growth, development, and stress adaptation of Arabidopsis (Arabidopsis thaliana), rice (Oryza sativa), and wheat (Triticum aestivum), the functions of CSDPs in other plants species, including cabbage (Brassica rapa), are largely unknown. To gain insight into the roles of CSDPs in cabbage under stress conditions, the genes encoding CSDPs in cabbage were isolated, and the functional roles of CSDPs in response to environmental stresses were analyzed. Real-time RT-PCR analysis revealed that the levels of BrCSDP transcripts increased during cold, salt, or drought stress, as well as upon ABA treatment. Among the five BrCSDP genes found in the cabbage genome, one CSDP (BRU12051), named BrCSDP3, was unique in that it is localized to the chloroplast as well as to the nucleus. Ectopic expression of BrCSDP3 in Arabidopsis resulted in accelerated seed germination and better seedling growth compared to the wild-type plants under high salt or dehydration stress conditions, and in response to ABA treatment. BrCSDP3 did not affect the splicing of intron-containing genes and processing of rRNAs in the chloroplast. BrCSDP3 had the ability to complement RNA chaperone-deficient Escherichia coli mutant cells under low temperatures as well as DNA- and RNA-melting abilities, suggesting that it possesses RNA chaperone activity. Taken together, these results suggest that BrCSDP3, harboring RNA chaperone activity, plays a role as a positive regulator in seed germination and seedling growth under stress conditions. PMID- 26263517 TI - Comprehensive analysis and expression profile of the homeodomain leucine zipper IV transcription factor family in tomato. AB - Homeodomain leucine zipper IV (HD-ZIP IV) proteins are plant-specific transcription factors that play important roles in development of epidermal cell layers and cuticle formation. The functions of two HD-ZIP IV family genes, CD2 and Wo, have been well characterized in tomato (Solanum lycopersicum). CD2 and Wo are involved in cuticle biosynthesis and trichome formation, respectively. In this study, we identified 13 novel tomato HD-ZIP IV (SlHDZIV) genes. We analyzed the structures, chromosome locations, phylogeny, protein motifs, and expression profiles of these SlHDZIV genes. Gene structure analysis revealed that a module of 11 exons and 10 introns existed in the SlHDZIV genes. These genes were asymmetrically distributed on chromosomes, except on chromosome 4 and 5. Segmental duplication possibly contributed to the expansion of tomato HD-ZIP IV genes. The expression profiles of these genes revealed their broad expression pattern and high expression in young leaves and flowers. Each gene responded to more than one of different phytohormones [abscisic acid, ethephon, 4-(indolyl) butyric acid, jasmonic acid, salicylic acid, gibberellic acid, and 6 benzylaminopurine] and four abiotic stress treatments (cold, heat, salt, and drought). This study provided significant insights into the diverse roles of SlHDZIV genes in tomato growth and development. PMID- 26263518 TI - De novo assembly and characterization of germinating lettuce seed transcriptome using Illumina paired-end sequencing. AB - At supraoptimal temperature, germination of lettuce (Lactuca sativa L.) seeds exhibits a typical germination thermoinhibition, which can be alleviated by sodium nitroprusside (SNP) in a nitric oxide-dependent manner. However, the molecular mechanism of seed germination thermoinhibition and its alleviation by SNP are poorly understood. In the present study, the lettuce seeds imbibed at optimal temperature in water or at supraoptimal temperature with or without 100 MUM SNP for different periods of time were used as experimental materials, the total RNA was extracted and sequenced, we gained 147,271,347 raw reads using Illumina paired-end sequencing technique and assembled the transcriptome of germinating lettuce seeds. A total of 51,792 unigenes with a mean length of 849 nucleotides were obtained. Of these unigenes, a total of 29,542 unigenes were annotated by sequence similarity searching in four databases, NCBI non-redundant protein database, SwissProt protein database, euKaryotic Ortholog Groups database, and NCBI nucleotide database. Among the annotated unigenes, 22,276 unigenes were assigned to Gene Ontology database. When all the annotated unigenes were searched against the Kyoto Encyclopedia of Genes and Genomes Pathway database, a total of 8,810 unigenes were mapped to 5 main categories including 260 pathways. We first obtained a lot of unigenes encoding proteins involved in abscisic acid (ABA) signaling in lettuce, including 11 ABA receptors, 94 protein phosphatase 2Cs and 16 sucrose non-fermenting 1-related protein kinases. These results will help us to better understand the molecular mechanism of seed germination, thermoinhibition of seed germination and its alleviation by SNP. PMID- 26263519 TI - Plastoquinone redox state modifies plant response to pathogen. AB - The role of PQ (plastoquinione) redox state in establishment of response to pathogen infection (Botrytis cinerea) was tested along the regulation of main antioxidative enzymes (superoxide dismutase - SOD, catalase - CAT) and photochemistry of PSII (photosystem II) in Mesembryanthemum crystallinum plants performing C3 and CAM (Crassulacean acid metabolism) carbon metabolism. The redox state of PQ was modified by two inhibitors of photosynthetic electron transport resulting in a more oxidised (3-(3,4-dichlorophenyl)-1,1-dimethylurea; DCMU) or reduced (2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone; DBMIB) PQ redox state simulating darkness and high light conditions, respectively. Irrespective of the type of treatment (mock inoculation or pathogen inoculation) SOD activity depended on the PQ pool. Our results suggest that regarding changes in infection induced CAT activity, plants developed response that is vital for hypersensitive like (HR-like) response establishment only when PQ pool generated signal was similar to that in light presence (DBMIB pre-treatment). When PQ pool generated signal was similar to darkness, CAT activity response remained stress independent, similarly to SOD. Fluorescence parameters of PSII, Qp (photochemical quenching coefficient) and NPQ (non-photochemical quenching) were affected only in the tissues treated with DCMU in stress-independent manner. We suggest that in case of abiotic and biotic stresses signals emerging from PQ pool indirectly orchestrate plant response and carbon metabolism affects this regulatory pathway. PMID- 26263520 TI - Capitol Success. AB - This legislative session, medicine resolved to ensure physicians can give their patients the best care possible. The hard work paid off in significant victories that largely build on the Texas Medical Association's 2013 legislative successes. PMID- 26263521 TI - Youth Safeguards, Budget Boons. AB - TMA, the Texas Public Health Coalition, and diligent physicians earned significant public health victories during the Texas Legislature's 2015 session in their drive to reduce tobacco and electronic cigarette use and to protect schoolchildren at risk for anaphylaxis. PMID- 26263522 TI - Medicaid Upgrade. AB - Enhancements to Medicaid's electronic enrollment portal aim to speed up the process as physicians face reenrollment in the program. PMID- 26263523 TI - Fair Evaluations, No Witch Hunts. AB - Physicians have greater protection against "sham" peer review thanks to a decision by the Texas Supreme Court. The decision will help physicians who believe business competitors or a hospital's administrators are using every means available to destroy their reputation. PMID- 26263524 TI - PsyCh Journal. Editorial. PMID- 26263525 TI - Prevention of depressive disorders in older adults: An overview. AB - Prevention of depressive disorders is one of the most important challenges for health care in coming decades. Depressive disorders in all age groups have a high disease burden and are associated with huge economic costs, and current treatments are only capable of taking away one-third of the (nonfatal) disease burden of depression under optimal conditions. Prevention may be one alternative strategy that may help in further reducing the disease burden of depression. Because of the worldwide increase in the number of older adults, the number of depressed older adults will also increase considerably in the next few decades, making prevention of depression an important priority for research. Identifying the high-risk target groups for preventive interventions is complicated because most risk indicators have a low specificity, indicating that most people from these groups will not develop the disorder despite increased risk levels. We describe one promising method to identify the best target groups, based on the principle that the high-risk group should be as small as possible, should be responsible for as many new cases of depression as possible, and that intervention be as effective as possible. The number of trials examining the possibility to prevent the onset of depressive disorders in those who do not (yet) meet diagnostic criteria for depression is increasing rapidly. A recent meta-analysis identified more than 30 randomized trials and these studies showed that the incidence of depressive disorders was 21% lower in the prevention groups compared with the control groups who did not receive the preventive intervention. Most of these trials are aimed at adolescents and younger adults. Only six trials were specifically aimed at older adults. The development of evidence-based preventive interventions for major depression and other mental disorders should be an important scientific and public health objective for the 21st century. PMID- 26263526 TI - Aging and the effects of emotion on cognition: Implications for psychological interventions for depression and anxiety. AB - We review findings from laboratory research on age differences in the effects of emotion on cognition. Particular attention is given to sadness leading to mood congruent memory and to anxiety leading to selective attention bias to threat. While older adults in normal moods show the positivity effect as expected from socio-emotional selectivity theory, older adults whose mood has changed from baseline to sad or anxious show these mood-related cognitive biases. These mood related biases are a foundational part of the theory underlying cognitive behavior therapy (CBT) and so these laboratory findings suggest ways that CBT may work differently with older adults. Pilot work suggests that the presence or absence of these effects may also predict responsiveness to treatment using CBT. PMID- 26263527 TI - Role conflict and satisfaction in the work-family context: Age differences in the moderating effect of role commitment. AB - This study examined age differences in the buffering effects of role commitment on the associations between role conflicts and satisfaction from the within domain and cross-domain perspectives. Eighty-five working mothers participated in the study. Multiple regression analyses revealed that work conflicts were negatively associated with job satisfaction of younger employees but not older employees. Commitment to both work and family buffered against the negative association between family conflicts and family satisfaction for older employees but not younger employees. These findings highlight the importance of role commitment for working mothers across adulthood to cope with the demands in the work-family interface. PMID- 26263528 TI - Interpretive bias of ambiguous facial expressions in older adults with depressive symptoms. AB - Cognitive theories of emotional disorders indicate that biases in cognitive processes, such as attention, memory, and interpretation, are common factors that indicate vulnerability to these disorders, although their form varies according to the type of disorder. However, most of the studies have focused on adolescence and adulthood. It is still uncertain whether cognitive biases are risk factors for late-life depression. The present study sought to explore the role of interpretive bias in older adults with depressive symptoms and whether this effect is independent of basic cognitive abilities. Therefore, 18 older adults with depressive symptoms and 21 healthy controls were compared with an ambiguous facial expression identification task, a Mini Mental Status Examination, a Trail Making Test A and B, and a Word Fluency Test. Findings revealed that the depressive group was more likely to identify more ambiguous happy-sad facial expressions as indicative of sadness than were the healthy controls, but the two groups showed no significant differences in the cognitive test scores. These results suggest that interpretive bias indicates vulnerability to late-life depression, but basic cognitive abilities may have no influence in this context. PMID- 26263529 TI - Testing a modified perceived exertion scale for Alzheimer's disease. AB - Standardized methods for prescribing and monitoring exercise intensity are needed to advance exercise research in Alzheimer's disease (AD). The purpose of this study was to evaluate the concurrent validity of a modified 1-10 Rating of Perceived Exertion (RPE) scale against heart rate (HR) in older adults with mild to-moderate AD (N = 8, age 77-87 years). RPE and HR were assessed every 5 min during each exercise session with 3,988 data pairs. Pearson and Spearman correlations and mixed models for correlated data were used for analysis. Results show the correlation between RPE and HR and between RPE and change in HR from resting was -.11 (SE = .15) and -.31 (SE = .17), respectively. The proportions of variance explained by RPE overall, RPE within participant, and RPE within session were only 4.0, 5.3, and 6.7%, respectively. We conclude that the modified 1-10 RPE scale did not show concurrent validity to HR, with large between-individual variability. PMID- 26263530 TI - Latent tuberculosis in kidney and liver transplant patients: a review of treatment practices and outcomes. AB - BACKGROUND: The standard treatment of latent tuberculosis infection (LTBI) is associated with toxicities and data are limited on tolerability among patients with advanced organ disease listed for transplant. Alternate options are available, but they have yet to be studied in this population. METHODS: A retrospective review of the treatment of LTBI among kidney and/or liver transplant candidates was conducted to assess factors impacting therapy initiation, tolerability, and completion of therapy. RESULTS: Of 174 eligible patients, treatment of LTBI was initiated in 129, of which 91 were listed for kidney transplant and 38 were listed for liver or liver/kidney transplant. Infectious Diseases consultation was independently associated with treatment initiation when controlling for waitlisted organ and receipt of hemodialysis (odds ratio [OR] 81.14, 95% confidence interval [CI] 23.94-274.94, P < 0.001). Documented completion of first-line therapy was 47% overall, and 49% and 39%, respectively, among kidney and liver/kidney candidates (P = not significant). On multivariable analysis, controlling for baseline aspartate aminotransferase and waitlisted organ, first-line receipt of rifampin was associated with lower rates of treatment completion (OR 0.19, 95% CI 0.05-0.77, P = 0.02). CONCLUSION: Based on medical record documentation, completion of first-line therapy was <50% in this cohort, although this is likely an underestimate, as 34% of patients had no chart documentation that therapy was completed. Approximately 20% of patients did not complete first-line therapy because of adverse effects. PMID- 26263531 TI - Human iPSC derived disease model of MERTK-associated retinitis pigmentosa. AB - Retinitis pigmentosa (RP) represents a genetically heterogeneous group of retinal dystrophies affecting mainly the rod photoreceptors and in some instances also the retinal pigment epithelium (RPE) cells of the retina. Clinical symptoms and disease progression leading to moderate to severe loss of vision are well established and despite significant progress in the identification of causative genes, the disease pathology remains unclear. Lack of this understanding has so far hindered development of effective therapies. Here we report successful generation of human induced pluripotent stem cells (iPSC) from skin fibroblasts of a patient harboring a novel Ser331Cysfs*5 mutation in the MERTK gene. The patient was diagnosed with an early onset and severe form of autosomal recessive RP (arRP). Upon differentiation of these iPSC towards RPE, patient-specific RPE cells exhibited defective phagocytosis, a characteristic phenotype of MERTK deficiency observed in human patients and animal models. Thus we have created a faithful cellular model of arRP incorporating the human genetic background which will allow us to investigate in detail the disease mechanism, explore screening of a variety of therapeutic compounds/reagents and design either combined cell and gene- based therapies or independent approaches. PMID- 26263532 TI - Retained in HIV Care But Not on Antiretroviral Treatment: A Qualitative Patient Provider Dyadic Study. AB - BACKGROUND: Patients retained in HIV care but not on antiretroviral therapy (ART) represent an important part of the HIV care cascade in the United States. Even in an era of more tolerable and efficacious ART, decision making in regards to ART offer and uptake remains complex and calls for exploration of both patient and provider perspectives. We sought to understand reasons for lack of ART usage in patients meeting the Health Resources Services Administration definition of retention as well as what motivated HIV primary care appointment attendance in the absence of ART. METHODS AND FINDINGS: We conducted a qualitative study consisting of 70 in-depth interviews with ART-naive and ART-experienced patients off ART and their primary care providers in two urban safety-net HIV clinics in San Francisco and New York. Twenty patients and their providers were interviewed separately at baseline, and 15 dyads were interviewed again after at least 3 mo and another clinic visit in order to understand any ART use in the interim. We applied dyadic analysis to our data. Nearly all patients were willing to consider ART, and 40% of the sample went on ART, citing education on newer antiretroviral drugs, acceptance of HIV diagnosis, social support, and increased confidence in their ability to adhere as facilitators. However, the strength of the provider recommendation of ART played an important role. Many patients had internalized messages from providers that their health was too good to warrant ART. In addition, providers, while demonstrating patient-centered care through sensitivity to patients experiencing psychosocial instability, frequently muted the offer of ART, at times unintentionally. In the absence of ART, lab monitoring, provider relationships, access to social services, opiate pain medications, and acute symptoms motivated care. The main limitations of this study were that treatment as prevention was not explored in depth and that participants were recruited from academic HIV clinics in the US, making the findings most generalizable to this setting. CONCLUSIONS: Provider communication with regard to ART is a key focus for further exploration and intervention in order to increase ART uptake for those retained in HIV care. PMID- 26263533 TI - Association analysis of the IL-1 gene cluster polymorphisms with aggressive and chronic periodontitis in the Algerian population. AB - OBJECTIVE: There is strong evidence that genetic as well as environmental factors affect the development of periodontitis. Various studies suggest that genetic polymorphisms of the interleukin-1 (IL-1) genes are associated with an increased risk of developing the pathogenesis. The aim of the present study was to investigate the possible relationship between two polymorphisms of IL-1 gene cluster IL-1B (C+3954T) (rs1143634) and IL-1A (C-889T) (rs1800587) SNPs and the aggressive and chronic periodontitis risk in a case control study in Algerian population. METHODS: 279 subjects were recruited and received a periodontal examination: 128 healthy controls and 151 cases. From cases, 91 patients were having a chronic disease whereas 60 subjects with aggressive form. All these subjects were genotyped for IL-1A (C-889T) and IL-1B (C+3954T) polymorphisms using TaqMan real time PCR technology. Frequencies of IL-1 alleles, genotypes and the haplotypes were also examined. RESULTS: Significant differences were found in the carriage rate of both minor alleles of the IL-1A (C-889T) and IL-1B (C+3954T) polymorphisms of aggressive periodontitis cases compared with healthy controls (OR [95%CI]=1.61 [1.03-2.49], p=0.03), (OR [95%CI]=1.69 [1.09-2.63], p=0.01), respectively. The result did not reach significance with the chronic form. CONCLUSION: The studied polymorphisms of the IL-1 genes appear to be associated with susceptibility to aggressive periodontitis (AgP) in the Algerian population. PMID- 26263534 TI - Effects of bleaching on laser Doppler blood-flow signals recorded from human teeth in vitro. AB - OBJECTIVE: To determine if bleaching a tooth affects significantly laser Doppler recordings of pulpal blood flow that are made through the treated enamel and dentine. DESIGN: Recordings of blood flow (flux) were made with a laser-Doppler flow meter from the crowns of 14, recently extracted, human premolars while diluted blood was pumped at three different rates through a cannula that was inserted into the pulp cavity with its tip in the coronal pulp chamber. The recordings of flux were made before and after bleaching the crown with 38% hydrogen peroxide for 30min. The colour changes produced by bleaching were also measured with a digital spectrophotometer in 15 teeth. The effects of bleaching on both blood flow recordings and tooth colour were studied in 11 of the teeth. RESULTS: Both before and after bleaching, there was a linear relationship between blood perfusion rate and flux. After bleaching, the flux readings increased by an average of 46%, and were significantly increased in every tooth (P<0.001, Wilcoxon Signed Rank Test). There was no significant correlation between the changes in flux and the changes in tooth colour. CONCLUSION: A laser Doppler flow meter cannot be used to determine the effect of bleaching on pulpal blood flow in intact teeth. PMID- 26263535 TI - Expression of translationally controlled tumor protein in heat-stressed human dental pulp cells. AB - OBJECTIVE: The aim of this study was to investigate the effects of heat stress on cell viability, translationally controlled tumor protein (TCTP) expression, and the effects of recombinant TCTP on heat-stressed human dental pulp cells (HDPCs). METHODS: HDPCs were isolated from human teeth and cultured at 37 degrees C. For heat stress, HPDCs were incubated at 43 degrees C for 45min. After heat stress, recombinant TCTP were added to HDPCs and cultured for various periods of time at 37 degrees C. Heat-treated cells were then analyzed by DNA staining with Hoechst 33258, MTT, and caspase 3 activity assays. TCTP expression level was assessed by real-time PCR and western blot analysis. RESULTS: Heat-treated cells displayed lower cell density and nuclear morphology resembling apoptotic body. Heat stress significantly decreased cell viability and induced activity of caspase 3. The effect of recombinant TCTP on pulp cell death from heat stress varied depending on each subject and TCTP concentration. Heat stress up-regulated TCTP mRNA expression level. In contrast, TCTP protein level remained unchanged. Recombinant TCTP did not affect TCTP mRNA expression but down-regulated TCTP protein in heat treated cells. CONCLUSIONS: Heat stress induces caspase 3 activation and up regulates TCTP mRNA expression in HDPCs. TCTP did not play a key role on pulp cell recovery from heat stress. PMID- 26263536 TI - Potential of an amelogenin based peptide in promoting reminerlization of initial enamel caries. AB - OBJECTIVE: In this study we give a preliminary study of a rationally designed small peptide, which is based on the enamel matrix protein amelogenin, to investigate its effect on remineralization of initial enamel caries lesions. DESIGN: A novel peptide was designed and synthesized to investigate its effects on the remineralization of initial enamel carious lesions during pH cycling that simulates intra-oral conditions. Initial lesions were created in bovine enamel blocks, which were then pH-cycled for 12 days in the presence of 25MUM peptide, 1g/L NaF (positive control), 50mM HEPES buffer(negative control). Before and after pH cycling, enamel blocks were analyzed by surface microhardness testing, polarized light microscopy and transverse microradiography. RESULTS: Percentage of surface microhardness recovery (SMHR%) after pH cycling was significantly higher in peptide group than HEPES group. Lower lesion depth and less mineral mineral loss were found in peptide or NaF treatment groups after the cycling, and were significantly different to HEPES group. No significant differences were observed between the blocks treated with peptide and those treated with NaF. CONCLUSSION: This study provides in vitro evidence that this amelogenin based peptide promotes enamel caries remineralization, offering a promising remineralizing biomaterial in initial enamel carious treatment. PMID- 26263537 TI - Protective efficacy of intravenous transplantation of adipose-derived stem cells for the prevention of radiation-induced salivary gland damage. AB - OBJECTIVE: High-dose radiation therapy in the head and neck area can lead to irreversible damage to salivary glands (SGs) with consequent xerostomia. Adipose derived stem cells (ADSCs) have been shown to repair or rescue damaged SGs. Thus, we investigated the protective efficacy of ADSCs in the prevention of SG damage induced by high dose radiation. METHODS: Third-passage ADSCs (1*10(6)) were transplanted by intravenous infusion into the tail-vein of 8-week-old C57BL/6 mice, immediately after local irritation at a dose of 18Gy. The process was repeated twice a week during a period of six consecutive weeks. Eight weeks after radiation, functional evaluations were conducted by measuring salivary flow rate (SFR). Histological, immunohistochemical and transmission electron microscopic (TEM) examinations were performed to analyze microstructural and ultrastructural changes, microvessel density, amylase production, apoptosis, and proliferation activity. RESULTS: Intravenously administrated ADSCs could home to irradiated SGs within 24h after infusion, significantly increasing SG weights, improving SFR, and preserving the microscopic morphologies of SGs eight weeks post-radiation. More functional acini, higher amylase production levels, and higher microvessel densities were observed in ADSC-treated SGs than in irradiated SGs. Additionally, enhanced cell proliferation activity and reduced radiation-induced SG apoptosis was observed in the ADSC-treated group when compared with the irradiated group. CONCLUSION: Systemic administration of ADSCs immediately after radiation at a dose of 18Gy can protect both the morphology and function of SGs eight weeks after radiation in mice, and can be used as a protective measure for the prevention of SG damage induced by high-dose radiation. PMID- 26263538 TI - An in vitro evaluation of the antibacterial properties of three mineral trioxide aggregate (MTA) against five oral bacteria. AB - OBJECTIVE: The purpose of this study was to evaluate the antibacterial ability of three MTA (MTA-Angelus, Endocem MTA, and ProRoot MTA) against five typical oral bacteria (Streptococcus mutans, Enterococcus faecalis, Lactobacillus rhamnosus, Lactobacillus paracasei, and Porphyromonas gingivalis). DESIGN: For disc diffusion test, each test material was placed into agar plates after inoculation of each bacterial strain. The zones of inhibition of bacterial growth were then measured. Antibacterial broth test was performed by adding the test material into the media. Colony-forming units were counted after incubation with bacteria. The data were analyzed using ANOVA and the Tukey's test. RESULTS: Disc diffusion test showed that the antibacterial activity against S. mutans, L. rhamnosus, L. paracasei, and P. gingivalis ranked in decreasing order of MTA-Angelus>ProRoot MTA>Endocem MTA (p<0.05). An inhibitory effect against E. faecalis was only observed in Endocem MTA. Antibacterial broth test showed that the antibacterial activity against all bacteria was Endocem MTA>MTA-Angelus>ProRoot MTA (p<0.05). CONCLUSION: Discrepant results were obtained from the disc diffusion and antibacterial broth test, with MTA-Angelus and Endocem MTA being most effective, respectively. Both tests revealed that the most resistant bacteria was E. faecalis, which was not susceptible at all, except to Endocem MTA in disc diffusion test. PMID- 26263539 TI - Novel biomarkers of periodontitis and/or obesity in saliva-An exploratory analysis. AB - OBJECTIVE: Recent studies point to the clinical and research utility of saliva as a valuable diagnostic aid for monitoring periodontal health. The objectives of this study were to detect novel biomarkers attributed to chronic inflammation in saliva and to determine if the levels of these markers correlate with severity of periodontitis and with standard obesity measures in participants in a periodontal maintenance program. DESIGN: In this cross-sectional assessment of 63 participants, unstimulated whole saliva was collected after recording anthropometric and clinical parameters of obesity and periodontitis, respectively. The levels of interleukin-1 receptor antagonist (IL-1ra), sCD40L, granzyme B and alpha-fetoprotein (AFP) in saliva were determined using multiplex proteomic immunoassays. The correlation between the four tested biomarker concentrations and obesity/periodontal measures was determined. RESULTS: Positive correlation between fat% and granzyme B levels (r=0.292; p=0.020) and negative correlation between BMI and sCD40L (r=0.256; p=0.043) was observed. In addition, positive correlation between severity of periodontal disease and levels of IL1-ra (r=0.253; p=0.046) and negative correlation between periodontitis severity and sCD40L salivary levels (r=0.272; p=0.031) was noted. None of the above correlations remained statistically significant after multiple comparisons adjustment. After adjustment for clinical covariates, the relationship between sCD40L and periodontal severity remained suggestive (p=0.081). CONCLUSIONS: Levels of four novel biomarkers of periodontitis were detectable in saliva of subjects enrolled in a periodontal maintenance program. Prospective studies with larger sample sizes and other populations are warranted to explore the diagnostic applicability of these markers. PMID- 26263540 TI - Expression of Pannexin3 in human odontoblast-like cells and its hemichannel function in mediating ATP release. AB - OBJECTIVE: The aim of this study is to investigate the expression of pannexin3 (Panx3) in human odontoblast-like cells (hOBs) and its hemichannel function in mediating ATP release. METHODS: RT-PCR and immunofluorescence analysis were used to detect the expression of pannexins (Panxs) in human dental pulp tissue and cultured cells. To determine the role of Panx3 in ATP release, hOBs were infected with Panx3-overexpression lentivirus, Panx3-shRNA lentivirus or control lentivirus and then stimulated with cold buffer. Intracellular ATP was monitored using quinacrine, and then semi-quantitatively analyzed. In the meantime, the ATP release was quantitatively analyzed using the bioluminescence method when the cells were exposed to cold stimulus. RESULTS: Panx3 mRNA and protein were found in dental pulp tissue and cultured cells. Upon cold stimulus, intracellular ATP was released into the extracellular space. Overexpression of Panx3 accelerated ATP release, whereas inhibition of Panx3 suppressed this process. CONCLUSION: Panx3 hemichannel is expressed in human odontoblast-like cells and mediates ATP release into the extracellular space. PMID- 26263541 TI - Stem cell regenerative therapy in alveolar cleft reconstruction. AB - Achieving a successful and well-functioning reconstruction of craniofacial deformities still remains a challenge. As for now, autologous bone grafting remains the gold standard for alveolar cleft reconstruction. However, its aesthetic and functional results often remain unsatisfactory, which carries a long-term psychosocial and medical sequelae. Therefore, searching for novel therapeutic approaches is strongly indicated. With the recent advances in stem cell research, cell-based tissue engineering strategies move from the bench to the patients' bedside. Successful stem cell engineering employs a carefully selected stem cell source, a biodegradable scaffold with osteoconductive and osteoinductive properties, as well as an addition of growth factors or cytokines to enhance osteogenesis. This review highlights recent advances in mesenchymal stem cell tissue engineering, discusses animal models and case reports of stem cell enhanced bone regeneration, as well as ongoing clinical trials. PMID- 26263542 TI - Comparison of osteo/odontogenic differentiation of human adult dental pulp stem cells and stem cells from apical papilla in the presence of platelet lysate. AB - INTRODUCTION: Human dental pulp cells (DPSCs) and stem cells from apical papilla have been used for the repair of damaged tooth tissues. Human platelet lysate (PL) has been suggested as a substitute for fetal bovine serum (FBS) for large scale expansion of dental stem cells. However, biological effects and optimal concentrations of PL for proliferation and differentiation of human dental stem cells remain to be elucidated. METHODOLOGY: DPSCs and SCAP cells were isolated from impacted third molars of young healthy donors, at the stage of root development and identified by markers using flow cytometry. For comparison the cells were cultured in media containing PL (1%, 5% and 10%) and FBS, with subsequent induction for osteogenic/odontogenic differentiation. The cultures were analyzed for; morphology, growth characteristics, mineralization potential (Alizarin Red method) and differentiation markers using ELISA and real time polymerase chain reaction (qPCR). RESULTS: The proliferation rates of DPSCs and SCAP significantly increased when cells were treated with 5% PL (7X doubling time) as compared to FBS. 5% PL also enhanced mineralized differentiation of DPSCs and SCAP, as indicated by the measurement of alkaline phosphatase activity, osteocalcin and osteopontin, calcium deposition and q-PCR. CONCLUSION: Our findings suggest that using 5% platelet lysate, proliferation and osteo/odontogenesis of DPSCs and SCAP for a short period of time (15 days), was significantly improved. This may imply its use as an optimum concentration for expansion of dental stem cells in bone regeneration. PMID- 26263543 TI - Dental stigmata and enamel thickness in a probable case of congenital syphilis from XVI century Croatia. AB - OBJECTIVE: To analyse the dental remains of an individual with signs of congenital syphilis by using macroscopic observation, CBCT and micro-CT images, and the analysis of the enamel thickness. DESIGN: Anthropological analysis of human skeletal remains from the 16th century archaeological site Park Gric in Zagreb, Croatia discovered a female, 17-20 years old at the time of death, with dental signs supportive of congenital syphilis: mulberry molars and canine defects, as well as non-specific hypoplastic changes on incisors. The focus of the analysis was on three aspects: gross morphology, hypoplastic defects of the molars, canines and incisors, as well as enamel thickness of the upper first and second molars. RESULTS: The observed morphology of the first molars corresponds to the typical aspect of mulberry molars, while that of the canines is characterised by hypomineralisation. Hypoplastic grooves were observed on the incisal edges of all incisors. The enamel of the first molars is underdeveloped while in the second molars a thick-enamelled condition is observed. CONCLUSIONS: Our observations for the dental and skeletal evidence are supportive to a diagnosis of congenital syphilis for this specimen from XVI century Croatia. The use of CT imaging helped documenting the diagnostic features and quantifying the effect of the dental stigmata on first molars. PMID- 26263544 TI - Synergistic effects of tea catechin epigallocatechin gallate and antimycotics against oral Candida species. AB - OBJECTIVE: Epigallocatechin gallate (EGCG), the major antimicrobial tea polyphenol, has been reported to inhibit the growth of Candida albicans planktonic cells and enhance the antifungal activity of antimycotics. We hypothesised that synergism exists between EGCG and conventional antimycotics against biofilms of Candida species. DESIGN: The minimal inhibitory concentrations (MIC) of EGCG, miconazole, fluconazole and amphotericin B against planktonic cells and the sessile MIC (SMIC) against biofilms of Candida albicans, Candida parapsilosis, Candida tropicalis, Candida glabrata, Candida kefyr and Candida krusei were determined by a microdilution method. For assessment of biofilm metabolic activity, the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H tetrazolium-5-carboxanilide (XTT) assay was used. The interactions between EGCG and antimycotics were evaluated by checkerboard microdilution assay and determined by fractional inhibitory concentration index (FIC). RESULTS: Synergism was observed between EGCG and miconazole, fluconazole or amphotericin B against most test planktonic and biofilm cells of Candida species (FIC<=0.5). All biofilm cells were significantly more resistant to EGCG and antimycotics (20-3200 times higher) compared with their planktonic counterparts. CONCLUSIONS: We conclude that EGCG enhances the antifungal effects of miconazole, fluconazole and amphotericin B. Combined treatment with EGCG may lower the dosages of antimycotics, thus preventing adverse effects and the emergence of drug-resistant oral Candida species. PMID- 26263545 TI - Experimentally induced stress decreases ideal female reproductive timing. AB - Previous correlational research shows that childhood adversity is associated with earlier age of reproduction in humans and other species. Such studies, however, cannot show that stressful conditions cause earlier reproduction. Using the cold pressor task, we built on previous work to test the idea that acute stress influences human reproductive and marital ideals, and that individual stress responses depend on adaptive life history strategies shaped by exposure to adversity during childhood. Acute stress shifted ideal ages of first birth and marriage to earlier ages. We also tested a competing hypothesis, whether stress had a more general impact on time preference, but found no evidence that it did. Furthermore, there was an interaction between childhood adversity and acute stress. Individuals who reported more exposure to childhood adversity responded to acute stress by reporting even earlier reproductive ideals. These findings offer experimental evidence that physiological stress can alter reproductive decision making in humans. PMID- 26263546 TI - Structure-Based Phylogenetic Analysis of the Lipocalin Superfamily. AB - Lipocalins constitute a superfamily of extracellular proteins that are found in all three kingdoms of life. Although very divergent in their sequences and functions, they show remarkable similarity in 3-D structures. Lipocalins bind and transport small hydrophobic molecules. Earlier sequence-based phylogenetic studies of lipocalins highlighted that they have a long evolutionary history. However the molecular and structural basis of their functional diversity is not completely understood. The main objective of the present study is to understand functional diversity of the lipocalins using a structure-based phylogenetic approach. The present study with 39 protein domains from the lipocalin superfamily suggests that the clusters of lipocalins obtained by structure-based phylogeny correspond well with the functional diversity. The detailed analysis on each of the clusters and sub-clusters reveals that the 39 lipocalin domains cluster based on their mode of ligand binding though the clustering was performed on the basis of gross domain structure. The outliers in the phylogenetic tree are often from single member families. Also structure-based phylogenetic approach has provided pointers to assign putative function for the domains of unknown function in lipocalin family. The approach employed in the present study can be used in the future for the functional identification of new lipocalin proteins and may be extended to other protein families where members show poor sequence similarity but high structural similarity. PMID- 26263548 TI - The Assessment of Muscular Effort, Fatigue, and Physiological Adaptation Using EMG and Wavelet Analysis. AB - Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1alpha) is a transcription factor co-activator that helps coordinate mitochondrial biogenesis within skeletal muscle following exercise. While evidence gleaned from submaximal exercise suggests that intracellular pathways associated with the activation of PGC-1alpha, as well as the expression of PGC-1alpha itself are activated to a greater extent following higher intensities of exercise, we have recently shown that this effect does not extend to supramaximal exercise, despite corresponding increases in muscle activation amplitude measured with electromyography (EMG). Spectral analyses of EMG data may provide a more in-depth assessment of changes in muscle electrophysiology occurring across different exercise intensities, and therefore the goal of the present study was to apply continuous wavelet transforms (CWTs) to our previous data to comprehensively evaluate: 1) differences in muscle electrophysiological properties at different exercise intensities (i.e. 73%, 100%, and 133% of peak aerobic power), and 2) muscular effort and fatigue across a single interval of exercise at each intensity, in an attempt to shed mechanistic insight into our previous observations that the increase in PGC-1alpha is dissociated from exercise intensity following supramaximal exercise. In general, the CWTs revealed that localized muscle fatigue was only greater than the 73% condition in the 133% exercise intensity condition, which directly matched the work rate results. Specifically, there were greater drop-offs in frequency, larger changes in burst power, as well as greater changes in burst area under this intensity, which were already observable during the first interval. As a whole, the results from the present study suggest that supramaximal exercise causes extreme localized muscular fatigue, and it is possible that the blunted PGC-1alpha effects observed in our previous study are the result of fatigue-associated increases in muscle acidosis. This should be explored in future research using further combinations of EMG and muscle biochemistry and histology. PMID- 26263547 TI - Spt-Ada-Gcn5-Acetyltransferase (SAGA) Complex in Plants: Genome Wide Identification, Evolutionary Conservation and Functional Determination. AB - The recruitment of RNA polymerase II on a promoter is assisted by the assembly of basal transcriptional machinery in eukaryotes. The Spt-Ada-Gcn5-Acetyltransferase (SAGA) complex plays an important role in transcription regulation in eukaryotes. However, even in the advent of genome sequencing of various plants, SAGA complex has been poorly defined for their components and roles in plant development and physiological functions. Computational analysis of Arabidopsis thaliana and Oryza sativa genomes for SAGA complex resulted in the identification of 17 to 18 potential candidates for SAGA subunits. We have further classified the SAGA complex based on the conserved domains. Phylogenetic analysis revealed that the SAGA complex proteins are evolutionary conserved between plants, yeast and mammals. Functional annotation showed that they participate not only in chromatin remodeling and gene regulation, but also in different biological processes, which could be indirect and possibly mediated via the regulation of gene expression. The in silico expression analysis of the SAGA components in Arabidopsis and O. sativa clearly indicates that its components have a distinct expression profile at different developmental stages. The co-expression analysis of the SAGA components suggests that many of these subunits co-express at different developmental stages, during hormonal interaction and in response to stress conditions. Quantitative real-time PCR analysis of SAGA component genes further confirmed their expression in different plant tissues and stresses. The expression of representative salt, heat and light inducible genes were affected in mutant lines of SAGA subunits in Arabidopsis. Altogether, the present study reveals expedient evidences of involvement of the SAGA complex in plant gene regulation and stress responses. PMID- 26263550 TI - Transcriptomic Analysis of Metabolic Pathways in Milkfish That Respond to Salinity and Temperature Changes. AB - Milkfish (Chanos chanos), an important marine aquaculture species in southern Taiwan, show considerable euryhalinity but have low tolerance to sudden drops in water temperatures in winter. Here, we used high throughput next-generation sequencing (NGS) to identify molecular and biological processes involved in the responses to environmental changes. Preliminary tests revealed that seawater (SW) acclimated milkfish tolerated lower temperatures than the fresh water (FW) acclimated group. Although FW- and SW-acclimated milkfish have different levels of tolerance for hypothermal stress, to date, the molecular physiological basis of this difference has not been elucidated. Here, we performed a next-generation sequence analysis of mRNAs from four groups of milkfish. We obtained 29669 unigenes with an average length of approximately 1936 base pairs. Gene ontology (GO) analysis was performed after gene annotation. A large number of genes for molecular regulation were identified through a transcriptomic comparison in a KEGG analysis. Basal metabolic pathways involved in hypothermal tolerance, such as glycolysis, fatty acid metabolism, amino acid catabolism and oxidative phosphorylation, were analyzed using PathVisio and Cytoscape software. Our results indicate that in response to hypothermal stress, genes for oxidative phosphorylation, e.g., succinate dehydrogenase, were more highly up-regulated in SW than FW fish. Moreover, SW and FW milkfish used different strategies when exposed to hypothermal stress: SW milkfish up-regulated oxidative phosphorylation and catabolism genes to produce more energy budget, whereas FW milkfish down regulated genes related to basal metabolism to reduce energy loss. PMID- 26263549 TI - Genetic Ancestry and Asthma and Rhinitis Occurrence in Hispanic Children: Findings from the Southern California Children's Health Study. AB - BACKGROUND: Asthma and rhinitis are common childhood health conditions. Being an understudied and rapidly growing population in the US, Hispanic children have a varying risk for these conditions that may result from sociocultural (including acculturative factors), exposure and genetic diversities. Hispanic populations have varying contributions from European, Amerindian and African ancestries. While previous literature separately reported associations between genetic ancestry and acculturation factors with asthma, whether Amerindian ancestry and acculturative factors have independent associations with development of early life asthma and rhinitis in Hispanic children remains unknown. We hypothesized that genetic ancestry is an important determinant of early-life asthma and rhinitis occurrence in Hispanic children independent of sociodemographic, acculturation and environmental factors. METHODS: Subjects were Hispanic children (5-7 years) who participated in the southern California Children's Health Study. Data from birth certificates and questionnaire provided information on acculturation, sociodemographic and environmental factors. Genetic ancestries (Amerindian, European, African and Asian) were estimated based on 233 ancestry informative markers. Asthma was defined by parental report of doctor-diagnosed asthma. Rhinitis was defined by parental report of a history of chronic sneezing or runny or blocked nose without a cold or flu. Sample sizes were 1,719 and 1,788 for investigating the role of genetic ancestry on asthma and rhinitis, respectively. RESULTS: Children had major contributions from Amerindian and European ancestries. After accounting for potential confounders, per 25% increase in Amerindian ancestry was associated with 17.6% (95% confidence interval [CI]: 0.74-0.99) and 13.6% (95% CI: 0.79-0.98) lower odds of asthma and rhinitis, respectively. Acculturation was not associated with either outcome. CONCLUSIONS: Earlier work documented that Hispanic children with significant contribution from African ancestry are at increased asthma risk; however, in Hispanic children who have little contribution from African ancestry, Amerindian ancestry was independently associated with lower odds for development of early-childhood asthma and rhinitis. PMID- 26263551 TI - A "footprint" of plant carbon fixation cycle functions during the development of a heterotrophic fungus. AB - Carbon fixation pathway of plants (CFPP) in photosynthesis converts solar energy to biomass, bio-products and biofuel. Intriguingly, a large number of heterotrophic fungi also possess enzymes functionally associated with CFPP, raising the questions about their roles in fungal development and in evolution. Here, we report on the presence of 17 CFPP associated enzymes (ten in Calvin Benson-Basham reductive pentose phosphate pathway and seven in C4-dicarboxylic acid cycle) in the genome of Sclerotinia sclerotiorum, a heterotrophic phytopathogenic fungus, and only two unique enzymes: ribulose-1, 5-bisphosphate carboxylase-oxygenase (Rubisco) and phosphoribulokinase (PRK) were absent. This data suggested an incomplete CFPP-like pathway (CLP) in fungi. Functional profile analysis demonstrated that the activity of the incomplete CLP was dramatically regulated during different developmental stages of S. sclerotiorum. Subsequent experiments confirmed that many of them were essential to the virulence and/or sclerotial formation. Most of the CLP associated genes are conserved in fungi. Phylogenetic analysis showed that many of them have undergone gene duplication, gene acquisition or loss and functional diversification in evolutionary history. These findings showed an evolutionary links in the carbon fixation processes of autotrophs and heterotrophs and implicated the functions of related genes were in course of continuous change in different organisms in evolution. PMID- 26263552 TI - Young women post-MI have higher plasma concentrations of interleukin-6 before and after stress testing. AB - OBJECTIVES: Young women have poorer prognosis after myocardial infarction (MI) and a higher rate of mental stress-induced ischemia compared with similarly aged men. A higher inflammatory status may help explain these sex differences. METHODS: We examined 98 patients (49 women and 49 men) age 18-59years with recent MI (past 6months). Women and men were matched for age, type of MI, and time since MI. Interleukin 6 (IL-6) concentrations were measured at baseline, after mental stress using a speech task, and after exercise/pharmacologic stress (60 and 90min). Depressive symptoms were measured with the Beck Depression Inventory (BDI II) and angiographic coronary artery disease (CAD) severity was quantified with the Gensini score. Single-photon emission computed tomography (SPECT) was used to obtain a computerized measurement of stress-induced ischemia (summed difference score, or SDS) and determine whether severity of stress-induced ischemia affects the inflammatory response to stress. Analysis was stratified by the median age of 50. Geometric mean concentrations of IL-6 were obtained from general linear regression models. RESULTS: In both age groups, women had less angiographic CAD and a similar level of conventional risk factors compared with men. Despite this, baseline IL-6 geometric means before both mental and physical stress were twice as high in women ?50years of age compared to age-matched men (3.8 vs. 1.8pg/mL, p=0.001, across both conditions), while they were similar in women and men age >50years (2.3 vs. 2.2pg/mL, p=0.83). After mental stress, IL-6 concentrations increased in both women and men in a similar fashion and remained twice as high in women ?50years than men at both 60min (5.4 vs. 2.6pg/mL, p=0.002) and 90min (5.9 vs. 3.4pg/mL, p=0.01). No significant difference was found between women and men >50years of age at any time point after mental stress. Results were similar for physical stress. After accounting for SDS, IL-6 concentrations in young women remained higher after both mental and physical stress. Baseline IL-6 concentrations were not significantly related to inducible ischemia. CONCLUSIONS: After MI, young women aged 50years or younger, compared with age-matched men, have remarkably higher concentrations of inflammation at baseline and after both mental and physical stress, with a similar inflammatory response to both stressors. Sustained concentrations of inflammation in young women, not their response to stress, may contribute to their adverse outcomes post-MI. PMID- 26263553 TI - Pre-Altitude Serum Ferritin Levels and Daily Oral Iron Supplement Dose Mediate Iron Parameter and Hemoglobin Mass Responses to Altitude Exposure. AB - PURPOSE: To investigate the influence of daily oral iron supplementation on changes in hemoglobin mass (Hbmass) and iron parameters after 2-4 weeks of moderate altitude exposure. METHODS: Hematological data collected from 178 athletes (98 males, 80 females) exposed to moderate altitude (1,350-3,000 m) were analysed using linear regression to determine how altitude exposure combined with oral iron supplementation influenced Hbmass, total iron incorporation (TII) and blood iron parameters [ferritin and transferrin saturation (TSAT)]. RESULTS: Altitude exposure (mean +/- s: 21 +/- 3 days) increased Hbmass by 1.1% [-0.4, 2.6], 3.3% [1.7, 4.8], and 4.0% [2.0, 6.1] from pre-altitude levels in athletes who ingested nil, 105 mg and 210 mg respectively, of oral iron supplement daily. Serum ferritin levels decreased by -33.2% [-46.9, -15.9] and 13.8% [-32.2, 9.7] from pre-altitude levels in athletes who supplemented with nil and 105 mg of oral iron supplement daily, but increased by 36.8% [1.3, 84.8] in athletes supplemented with 210 mg of oral iron daily. Finally, athletes who ingested either 105 mg or 210 mg of oral iron supplement daily had a greater TII compared with non-supplemented athletes (0 versus 105 mg: effect size (d) = -1.88 [-2.56, 1.17]; 0 versus 210 mg: effect size (d) = -2.87 [-3.88, -1.66]). CONCLUSION: Oral iron supplementation during 2-4 weeks of moderate altitude exposure may enhance Hbmass production and assist the maintenance of iron balance in some athletes with low pre-altitude iron stores. PMID- 26263554 TI - Phenotypic and Genetic Characterization of Avian Influenza H5N2 Viruses with Intra- and Inter-Duck Variations in Taiwan. AB - BACKGROUND: Human infections with avian influenza viruses (AIVs) have frequently raised global concerns of emerging, interspecies-transmissible viruses with pandemic potential. Waterfowl, the predominant reservoir of influenza viruses in nature, harbor precursors of different genetic lineages that have contributed to novel pandemic influenza viruses in the past. METHODS: Two duck influenza H5N2 viruses, DV518 and DV413, isolated through virological surveillance at a live poultry market in Taiwan, showed phylogenetic relatedness but exhibited different replication capabilities in mammalian Madin-Darby Canine Kidney (MDCK) cells. This study characterizes the replication properties of the two duck H5N2 viruses and the determinants involved. RESULTS: The DV518 virus replicated more efficiently than DV413 in both MDCK and chicken DF1 cells. Interestingly, the infection of MDCK cells by DV518 formed heterogeneous plaques with great differences in size [large (L) and small (S)], and the two viral strains (p518-L and p518-S) obtained from plaque purification exhibited distinguishable replication kinetics in MDCK cells. Nonetheless, both plaque-purified DV518 strains still maintained their growth advantages over the plaque-purified p413 strain. Moreover, three amino acid substitutions in PA (P224S), PB2 (E72D), and M1 (A128T) were identified in intra-duck variations (p518-L vs p518-S), whereas other changes in HA (N170D), NA (I56T), and NP (Y289H) were present in inter-duck variations (DV518 vs DV413). Both p518-L and p518-S strains had the N170D substitution in HA, which might be related to their greater binding to MDCK cells. Additionally, polymerase activity assays on 293T cells demonstrated the role of vRNP in modulating the replication capability of the duck p518-L viruses in mammalian cells. CONCLUSION: These results demonstrate that intra-host phenotypic variation occurs even within an individual duck. In view of recent human infections by low pathogenic AIVs, this study suggests possible determinants involved in the stepwise selection of virus variants from the duck influenza virus population which may facilitate inter-species transmission. PMID- 26263555 TI - LTBP-2 Has a Single High-Affinity Binding Site for FGF-2 and Blocks FGF-2-Induced Cell Proliferation. AB - Latent transforming growth factor-beta-1 binding protein-2 (LTBP-2) belongs to the fibrillin-LTBP superfamily of extracellular matrix proteins. LTBPs and fibrillins are involved in the sequestration and storage of latent growth factors, particularly transforming growth factor beta (TGF-beta), in tissues. Unlike other LTBPs, LTBP-2 does not covalently bind TGF-beta, and its molecular functions remain unclear. We are screening LTBP-2 for binding to other growth factors and have found very strong saturable binding to fibroblast growth factor 2 (FGF-2) (Kd = 1.1 nM). Using a series of recombinant LTBP-2 fragments a single binding site for FGF-2 was identified in a central region of LTBP-2 consisting of six tandem epidermal growth factor-like (EGF-like) motifs (EGFs 9-14). This region was also shown to contain a heparin/heparan sulphate-binding site. FGF-2 stimulation of fibroblast proliferation was completely negated by the addition of 5-fold molar excess of LTBP-2 to the assay. Confocal microscopy showed strong co localisation of LTBP-2 and FGF-2 in fibrotic keloid tissue suggesting that the two proteins may interact in vivo. Overall the study indicates that LTBP-2 is a potent inhibitor of FGF-2 that may influence FGF-2 bioactivity during wound repair particularly in fibrotic tissues. PMID- 26263557 TI - Infection Profiles of Selected Aquabirnavirus Isolates in CHSE Cells. AB - The wide host range and antigenic diversity of aquabirnaviruses are reflected by the presence of a collection of isolates with different sero- and genotypic properties that have previously been classified as such. Differences in cytopathogenic mechanisms and host responses induced by these isolates have not been previously examined. In the present study, we investigated infection profiles induced by genetically and serologically closely related as well as distant isolates in-vitro. CHSE-214 cells were infected with either E1S (serotype A3, genogroup 3), VR-299 (serotype A1, genogroup 1), highly virulent Sp (TA) or avirulent Sp (PT) (serotype A2, genogroup 5). The experiments were performed at temperatures most optimum for each of the isolates namely 15 degrees C for VR 299, TA and PT strains and 20 degrees C for E1S. Differences in virus loads and ability to induce cytopathic effect, inhibition of protein synthesis, apoptosis, and induction of IFNa, Mx1, PKR or TNFalpha gene expression at different times post infection were examined. The results showed on one hand, E1S with the highest ability to replicate, induce apoptosis and IFNa gene expression while VR 299 inhibited protein synthesis and induced Mx1 and PKR gene expression the most. The two Sp isolates induced the highest TNFalpha gene expression but differed in their ability to replicate, inhibit protein synthesis, and induce gene expression, with TA being more superior. Collectively, these findings point towards the adaptation by different virus isolates to suit environments and hosts that they patronize. Furthermore, the results also suggest that genetic identity is not prerequisite to functional similarities thus results of one aquabirnavirus isolate cannot necessarily be extrapolated to another. PMID- 26263559 TI - The Abridgment and Relaxation Time for a Linear Multi-Scale Model Based on Multiple Site Phosphorylation. AB - Random effect in cellular systems is an important topic in systems biology and often simulated with Gillespie's stochastic simulation algorithm (SSA). Abridgment refers to model reduction that approximates a group of reactions by a smaller group with fewer species and reactions. This paper presents a theoretical analysis, based on comparison of the first exit time, for the abridgment on a linear chain reaction model motivated by systems with multiple phosphorylation sites. The analysis shows that if the relaxation time of the fast subsystem is much smaller than the mean firing time of the slow reactions, the abridgment can be applied with little error. This analysis is further verified with numerical experiments for models of bistable switch and oscillations in which linear chain system plays a critical role. PMID- 26263556 TI - Transcriptomic Profiling and H3K27me3 Distribution Reveal Both Demethylase Dependent and Independent Regulation of Developmental Gene Transcription in Cell Differentiation. AB - The removal of histone H3 trimethylation at lysine residue 27 (H3K27me3) plays a critical role in the transcriptional initiation of developmental genes. The H3K27me3-specific KDM6 demethylases JMJD3 and UTX are responsible for the transcriptional initiation of various developmental genes, but some genes are expressed in a KDM6 demethylase-independent manner. To address the role of H3K27me3 in the retinoic acid (RA)-induced differentiation of the human carcinoma NCCIT cell line, we inhibited JMJD3 and UTX using the H3K27me3 demethylase inhibitor GSK-J4. The commitment of JMJD3/UTX-inhibited cells to a specific fate was delayed, and transcriptome profiling also revealed the differential expression of genes related to cell fate specification in demethylase-inactivated cells; the expression levels of RA metabolism and HOX family genes significantly decreased. We observed a weak correlation between H3K27me3 enrichment and transcriptional repression in the control and JMJD/UTX-inhibited cells, except for a few sets of developmental genes that are indispensable for cell fate specification. Taken together, these results provide the H3K27me3 landscape of a differentiating cell line and suggest that both demethylase-dependent and demethylase-independent transcriptional regulation play a role in early differentiation and developmental gene expression activated by H3K27me3 demethylation. PMID- 26263558 TI - Cox4i2, Ifit2, and Prdm11 Mutant Mice: Effective Selection of Genes Predisposing to an Altered Airway Inflammatory Response from a Large Compendium of Mutant Mouse Lines. AB - We established a selection strategy to identify new models for an altered airway inflammatory response from a large compendium of mutant mouse lines that were systemically phenotyped in the German Mouse Clinic (GMC). As selection criteria we included published gene functional data, as well as immunological and transcriptome data from GMC phenotyping screens under standard conditions. Applying these criteria we identified a few from several hundred mutant mouse lines and further characterized the Cox4i2tm1Hutt, Ifit2tm1.1Ebsb, and Prdm11tm1.1ahl lines following ovalbumin (OVA) sensitization and repeated OVA airway challenge. Challenged Prdm11tm1.1ahl mice exhibited changes in B cell counts, CD4+ T cell counts, and in the number of neutrophils in bronchoalveolar lavages, whereas challenged Ifit2tm1.1Ebsb mice displayed alterations in plasma IgE, IgG1, IgG3, and IgM levels compared to the challenged wild type littermates. In contrast, challenged Cox4i2tm1Hutt mutant mice did not show alterations in the humoral or cellular immune response compared to challenged wild type mice. Transcriptome analyses from lungs of the challenged mutant mouse lines showed extensive changes in gene expression in Prdm11tm1.1ahl mice. Functional annotations of regulated genes of all three mutant mouse lines were primarily related to inflammation and airway smooth muscle (ASM) remodeling. We were thus able to define an effective selection strategy to identify new candidate genes for the predisposition to an altered airway inflammatory response under OVA challenge conditions. Similar selection strategies may be used for the analysis of additional genotype-envirotype interactions for other diseases. PMID- 26263562 TI - Laboratory response to the West African Ebola outbreak 2014-2015. PMID- 26263563 TI - Plans for containment of poliovirus following type-specific polio eradication worldwide, 2015. PMID- 26263564 TI - The Art of Medicine. Traveling exhibit at Alpert Medical School offers portraits of rare diseases. PMID- 26263565 TI - Retraction. PMID- 26263566 TI - The reality of virtual dentistry. PMID- 26263567 TI - Interdisciplinary Approach to Care: Collaboration, "Listening," and the Patient's Needs. PMID- 26263568 TI - [An autopsy case of amyotrophic lateral sclerosis presenting with flail arm syndrome and rapid progression of respiratory failure]. PMID- 26263569 TI - Reply: To PMID 25492070. PMID- 26263570 TI - Introduction to the 2014 IUS Special Issue on Ultrasonics. PMID- 26263571 TI - Numerical Analysis of Ultrasound Backscattered Waves in Cancellous Bone Using a Finite-Difference Time-Domain Method: Isolation of the Backscattered Waves From Various Ranges of Bone Depths. AB - Using a finite-difference time-domain method, ultrasound backscattered waves inside cancellous bone were numerically analyzed to investigate the backscatter mechanism. Two bone models with different thicknesses were modeled with artificial absorbing layers positioned at the back surfaces of the model, and an ultrasound pulse wave was transmitted toward the front surface. By calculating the difference between the simulated waveforms obtained using the two bone models, the backscattered waves from a limited range of depths in cancellous bone could be isolated. The results showed that the fast and slow longitudinal waves, which have previously been observed only in the ultrasound waveform transmitted through the bone, could be distinguished in the backscattered waveform from a deeper bone depth when transmitting the ultrasound wave parallel to the main orientation of the trabecular network. The amplitudes of the fast and slow backscattered waves were more closely correlated with the bone porosity [R2 = 0.84 and 0.66 (p < 0.001), respectively] than the amplitude of the whole (nonisolated) backscattered waves [R2 = 0.48 (p < 0.001)]. In conclusion, the nonisolated backscattered waves could be regarded as the superposition of the fast and slow waves reflected from various bone depths, returning at different times. PMID- 26263573 TI - Erratum and Addendum. Molecular analysis of Nogo expression in the hippocampus during development and following lesion and seizure. Retraction of a retraction. PMID- 26263572 TI - The Authors' Reply. PMID- 26263574 TI - On Being Mortal.... PMID- 26263577 TI - Late Effects of Radiation Therapy in Pediatric Cancer Survivors. AB - The overall survival rates of many pediatric cancers continue to improve with each decade due to new advances in therapy. As this trend continues, the focus and importance of minimizing acute and long-term toxicity associated with treatment is paramount. While significant research regarding many of the late responses of normal tissues associated with radiation exposure has been established, future endeavors must be directed toward the identification of therapy related factors including radiation total dose, dose rate, exposure, and target treatment volumes. Awareness of short and long-term health risks of these patients is important and careful follow-up of long-term survivors is essential. In this report, we review some selected late adverse effects including the development of secondary malignancies, cardiotoxicity, physiological changes to glandular tissue, hormonal and reproductive changes to germ cells, and neurocognitive changes. Furthermore, we compared the differences regarding late effects of normal tissues associated with the use of proton versus photon radiotherapy, a topic that has received a great deal of attention in pediatric cancer and is increasing in utilization in the United States and world-wide. PMID- 26263578 TI - The Approach to Depression in the Primary Care Setting. PMID- 26263579 TI - Ear, Nose and Throat Nursing Foundation (ENT-NF). PMID- 26263580 TI - Issues Faced by Family Caregivers of Hospice Patients with Head and Neck Cancers. AB - PURPOSE: The purpose of this study was to explore issues reported by caregivers of Head and Neck cancer (HNC) patients newly admitted to hospice homecare. METHODS: 26 caregivers providing hospice homecare to patients with HNC were induded. Caregiver depressive symptoms, social support and perceived health data were analyzed. RESULTS: The caregivers reported few depressive symptoms, good perceived social support, and good perceived health; however, there was large variation in the group with some individuals having significant problems. DISCUSSION: Caregivers appeared to be doing well physically, emotionally and socially, but baseline data were used, so follow-up data are needed. Further research is warranted. CONCLUSIONS: Family caregivers also are affected by the experience of cancer and may have depressive symptoms needing assessment and management. Hospice patients with HNC have a variety of symptoms specific to their disease and treatment that need assessment and management by their family caregivers. Caregivers of HNC patients in hospice and palliative care need and deserve attention from hospice providers as they care for patients. PMID- 26263581 TI - Early Intervention for Neonatal Ear Deformities. PMID- 26263582 TI - The Power of Gratitude to Nurses. PMID- 26263583 TI - Nurses and Lobbying. PMID- 26263584 TI - Open Access to research findings and Community Dental Health. PMID- 26263585 TI - Tackling a dry mouth: an oral health intervention for Sjogren's sufferers. PMID- 26263587 TI - The relationship between tooth loss and psychological factors. AB - OBJECTIVES: Limited evidence is available regarding mutual interactions between psychological factors and tooth loss. This study aimed to investigate the association between these two issues. METHOD: In this 2011 cross-sectional study we obtained data from 4,585 adults who had completed information in 20 counties across Isfahan province, Iran, regarding tooth loss and psychological factors (depression, anxiety and stress level). To analyse the data ANOVA and multiple ordinal regression were applied. RESULTS: After adjusting socio demographic factors, the association between depression (OR 1.23; 95% CI = 1.01,1.49), anxiety (OR 1.19; 95% CI = 1.03,1.38), and high stress level (OR 95% CI = 1.19; 1.01,1.39) remained significant. CONCLUSION: We confirm the interaction between psychological factors and tooth loss, but recommend further studies on a national Iranian population. PMID- 26263586 TI - Fractional Urinary Fluoride Excretion (FUFE) of 3-4 year children in the Gaza Strip. AB - A positive association between dental fluorosis prevalence and fluoride (F) concentration in drinking waters has been detected in Gaza Strip. Total Daily Fluoride Retention (TDFR), and Fractional Urinary Fluoride Excretion (FUFE) indicate F body burden; important in assessing fluorosis risk in susceptible age groups. OBJECTIVE: 1, To determine and compare Daily Urinary Fluoride Excretion (DUFE) and FUFE of 3-4-year-olds living in lower (< 0.7), moderate (0.7-1.2) or higher (> 1.2 ) ppm F tap water areas; 2, To determine any relationship between i, DUFE and tap water F; ii, DUFE and Total Daily Fluoride Intake (TDFI); iii, TDFI and TDFR. METHODS: 24-hour urine and tap water samples were collected from 216 children exposed to lower (n = 81), moderate (n = 72), or higher (n = 63) tap water F. ANOVA with Tukey's Test and Pearson's correlation were used to examine differences in mean DUFE and FUFE and relationships between variables. RESULTS: Mean drinking water F was 0.11(sd 0.17), 0.14 (sd 0.28) and 0.38 (sd 0.63) ppmF respectively. Differences (p < 0.0001) in mean DUFEs (0.17 (sd 0.13), 0.25 (sd 0.15) and 0.38 (sd 0.23) mg/day respectively) and mean FUFEs (48 (sd 39)%, 47 (sd 31)% and 63(sd 76)%) were found (p < 0.05). Significant (p < 0.0001) positive correlations were found between DUFE and tap water F; DUFE and TDFI, and; TDFI and TDFR. CONCLUSION: DUFEs of children drinking waters with 0.11 and 0.14ppm F, represented low F usage. The group drinking 0.38ppm F water represented optimal F usage. The weak significant positive association of DUFE with home tap water F suggests low validity for tap water F in estimating F exposure. PMID- 26263588 TI - Comparing lifecourse models of social class and adult oral health using the 1958 National Child Development Study. AB - OBJECTIVE: To identify the lifecourse model that best describes the association between social class and adult oral health. METHODS: Data from 10,217 participants of the 1958 National Child Development Study were used. Social class at ages 7, 16 and 33 years were chosen to represent socioeconomic conditions during childhood, adolescence and adulthood, respectively. Two subjective oral health indicators (lifetime and past-year prevalence of persistent trouble with gums or mouth) were measured at age 33. The critical period, accumulation and social trajectories models were tested in logistic regression models and the most appropriate lifecourse model was identified using the structured modelling approach. RESULTS: The critical period model showed that only adulthood social class was significantly associated with oral health. For the accumulation model, a monotonic gradient was found between the number of periods in manual social class and oral health; and four out of eight social trajectories were found to be distinctive. Finally, the social trajectories model was not significantly different from the saturated model indicating that it provided a good fit to the data. CONCLUSION: This study shows the social trajectories model was the most appropriate, in terms of model fit, to describe the association between social class and oral health. PMID- 26263590 TI - Barriers to providing oral health care to pre-school children-differences between paediatric dentists' and general dental practitioners' beliefs. AB - BACKGROUND: The unmet dental needs of pre-school children indicate there are barriers in 'accessing' appropriate oral health care and this warrants consideration of care providers' beliefs. OBJECTIVE: To explore the beliefs and attitudes of dentists in Hong Kong towards providing oral health care to pre school children; and to determine difference in attitudes between general dental practitioners (GDPs) and paediatric dentists (PDs). METHODS: A random sample of 476 GDPs (-25% of all registered dentists) and all registered PDs (28) were invited to participate in the study. Both groups were asked to complete the Barriers to Childhood Caries Treatment (BaCCT) questionnaire: a 29-item measure considering child, parent, dentist and health care system factors. Differences in attitudes of GDPs and PDs were examined in bivariate and regression analyses. RESULTS: The overall response rate of the study was 61.5% (310/504). There were significant differences in overall BaCCT scores and across all domains between GDPs and PDs (p < 0.05). Furthermore, variations across many aspects (as described at an item level) were apparent. Regression analyses confirmed differences in BaCCT between GDPs and PDs, controlling for practice and other factors. CONCLUSIONS: Differences exist between GDPs' and PDs' perceptions of barriers to care for early childhood caries. This has implications for how to address 'access' issues with likely implications on how to overcome barriers to care for pre-school children. PMID- 26263589 TI - Socioeconomic inequalities in oral health among adults in Tehran, Iran. AB - OBJECTIVE: To identify the socioeconomic distribution of perceived oral health among adults in Tehran, Iran. BASIC RESEARCH DESIGN: A cross-sectional population study. PARTICIPANTS: A stratified random sample of 1,100 adults aged 18-84 years living in Tehran. METHODS: Self-report data were obtained from the 2010 dental telephone interview survey. Oral health was evaluated using self-assessed non replaced extracted teeth (NRET), and a three-item perceived dental health instrument. Socioeconomic status was measured by combining the variables of education and assets using principal component analysis. Inequalities in oral health were examined using prevalence ratios and concentration index. RESULTS: The poorest quintile was 1.60 (95% confidence interval, CI, 1.30; 1.98) times as likely to have any NRET compared with the richest quintile, indicating a disparity. Inequality was most pronounced in the 35-59 age group with prevalence ratio 2.01 (95% CI 1.26; 3.05). The concentration index of NRET in adults in Tehran was -0.22 (95% CI -0.28; -0.16). No significant differences were found in perceived dental health between socioeconomic classes. CONCLUSIONS: Adults from lower socioeconomic classes experienced more disabilities due to missing their teeth, specifically in the middle-age group. Inequalities in perceived dental health were not apparent in the studied population. PMID- 26263591 TI - Health economic analyses of domiciliary dental care and care at fixed clinics for elderly nursing home residents in Sweden. AB - OBJECTIVES: Dental care for elderly nursing home residents is traditionally provided at fixed dental clinics, but domiciliary dental care is an emerging alternative. Longer life expectancy accompanied with increased morbidity, and hospitalisation or dependence on the care of others will contribute to a risk for rapid deterioration of oral health so alternative methods for delivering oral health care to vulnerable individuals for whom access to fixed dental clinics is an obstacle should be considered. The aim was to analyse health economic consequences of domiciliary dental care for elderly nursing home residents in Sweden, compared to dentistry at a fixed clinic. METHODS: A review of relevant literature was undertaken complemented by interviews with nursing home staff, officials at county councils, and academic experts in geriatric dentistry. Domiciliary dental care and fixed clinic care were compared in cost analyses and cost-effectiveness analyses. RESULTS: The mean societal cost of domiciliary dental care for elderly nursing home residents was lower than dental care at a fixed clinic, and it was also considered cost-effective. Lower cost of dental care at a fixed dental clinic was only achieved in a scenario where dental care could not be completed in a domiciliary setting. CONCLUSIONS: Domiciliary dental care for elderly nursing home residents has a lower societal cost and is cost effective compared to dental care at fixed clinics. To meet current and predicted need for oral health care in the ageing population alternative methods to deliver dental care should be available. PMID- 26263592 TI - School-based intervention for improving the oral health of children in southern Thailand. AB - OBJECTIVE: A two-year study assessed the benefit of an enhanced oral health promotion program combined with a closely supervised tooth brushing program in schools, using toothpaste containing 1,450 ppm F- and 1.5% arginine, on oral health and dental caries. METHODS: 15 southern Thailand schools and 3,706 pre school children were recruited: 8 schools with 1,766 children as controls; 7 schools with 1,940 children in the intervention groups. Of the intervention schools five were classified as cooperative school and two as non-cooperative schools, based on the criteria of 80% participation in the prescribed tooth brushing activities. RESULTS: The DMFT and DMFS increments ("enamel and dentine") were 1.19 and 1.91 for the control group and 1.04 and 1.59 for the intervention groups. These represent 12.6% and 16.8% reductions in caries respectively. The DMFT and DMFS increments ("dentine threshold") were 0.26 and 0.44 for the control group and 0.19 and 0.29 for the intervention group, representing 26.9%, and 34.1% reductions in caries incidence respectively. For the more cooperative schools the benefits were greater: up to a 40.9% reduction in caries for DMFS ("dentine threshold"). At the 24 month examination there were significant improvements in dental plaque scores with greater improvements seen in the intervention group, greater still in the cooperative schools. CONCLUSIONS: This study documents the positive effect from use of fluoridated toothpaste (1,450 ppm F- and 1.5% arginine) administered by schoolteachers and undertaken via an enhanced school oral health program. Optimising oral health interventions for young children in Thai schools may have a significant impact on caries incidence resulting in reductions of up to 34% reductions in caries for all schools included in the study and up to 41% for the most cooperative. PMID- 26263593 TI - Tooth brushing among 11- to 15-year-olds in Denmark: combined effect of social class and migration status. AB - OBJECTIVE: Regular tooth brushing in adolescence predicts stable tooth brushing habits later in life. Differences in tooth brushing habits by ethnic background and socioeconomic position have been suggested. We investigated migration status and social class in relation to infrequent tooth brushing both separately and combined. METHODS: The study population was 11-15 year-olds chosen from a clustered random sample of schools. Univariate and multivariate logistic regression analyses estimated the separate and combined effects of migration status and social class on less than twice daily tooth brushing. RESULTS: 10,607 respondents: a response rate of 88.3%. Boys of lower social class had higher odds ratio (OR) of infrequent tooth brushing than girls: 1.98 (95% confidence interval 1.62-2.41) vs 1.80 (1.53-2.24). Immigrants and descendants had higher odds compared to adolescents of Danish origin: immigrant boys OR 1.39 (1.05-1.89), girls OR 1.92 (1.47-2.50); descendant boys OR 2.53 (1.97-3.27), girls OR 2.56 (2.02-3.35). Analyses of the combined effect of social class and migration status showed that the social gradient in tooth brushing habits observed among ethnic Danes cannot be found among groups of immigrants and descendants. CONCLUSION: The study shows that both non-Danish origin and low social class increases the risk of infrequent tooth brushing among school-aged children. The study calls for in depth analyses of the processes which influence young people's tooth brushing habits. Further, there is a need to strengthen the promotion of appropriate tooth brushing habits of minority and low social class youths. PMID- 26263594 TI - The incidence and nature of complaints against dentists for the treatment of children in Israel from 1992-2011. AB - OBJECTIVES: Medical literature lacks information about complaints against dentists who treat children. The present study aimed to evaluate the reports filed to Medical Consultant International (MCI) regarding paediatric dentistry in 1992-2011. BASIC RESEARCH DESIGN: Most dentists in Israel (85%) are obliged by their professional liability insurance policy to report adverse events to MCI. Reports were analysed using a structured form that included demographic details of the treating dentist, patients and parents, type of treatment, the result and the dentist's attitude. MCI dental consultants' decisions were evaluated by two specialists in paediatric dentistry. RESULTS: The number of complaints per year is increasing. Complaints involved maltreatment (33%), case mismanagement (25%) and complications that required additional treatment (26%). Communication was problematic in 60% of cases. Only 16.7% of complaints developed into an actual lawsuit. Most complaints were against female general practitioners and against dentists who worked in community dental clinics located in peripheral areas. Treating permanent teeth increased to 3.6 times the probability of developing into a lawsuit. 59% of event records had missing data. Seventy-five percent of the cases rose from elective treatments while 25% concerned emergency treatments. One third of the cases required additional treatment in a hospital i.e. abscess drainage, foreign body swallowing or other physical damages. CONCLUSIONS: Better case selection and documentation, better training of dentists who treat children and more appropriate attitude toward patients and parents, are likely to reduce the number of complaints. PMID- 26263595 TI - Treatment provided in the Public Dental Service in Finland in 2009. AB - OBJECTIVES: To analyse treatment measures provided in the Public Dental Service (PDS) and to discuss the therapy given against treatment needs as expressed in the national clinical epidemiological studies. METHODS: In 2009, the Chief Dentists of the PDS units collected data from their local registers on patients and treatment provided. Data were obtained from 166 PDS units (86%). Treatment patterns were compared between age groups, provider groups and geographical areas using chi-square tests. RESULTS: Altogether 8.9 million treatments were provided for 1.7 million patients. Examinations, restorative treatment and anaesthesia accounted for 61.3% of all treatments. Preventive measures (8.4%) and periodontal treatment (6.3%) were small proportions of the total. Prosthetic treatment was uncommon (0.5%). Working age adults received half of all treatments (53.2%), the young a third (36.4%) and the elderly 10.4%. Dental hygienists or dental assistants provided 29.7% of all treatment for children and adolescents, 11.1% for adults and 14.1% for the elderly. CONCLUSION: Relatively healthy children had plenty of examinations and preventive measures, and adults had mostly restorative care when their needs were more periodontal and prosthetic care, indicating that treatment given was not fully in line with needs. PMID- 26263596 TI - Advancing the scientific basis of oral health education. PMID- 26263597 TI - Improving access to dental care for vulnerable children; further development of the Back2School programme in 2013. AB - This paper describes a service evaluation of a dental treatment programme providing care to children not normally taken to the dentist. It explains the extension of the Back2School programme from the pilot phase and assesses if a mobile dental unit (MDU) can provide a high quality service. The public health competencies it illustrates include oral health improvement, developing and monitoring quality dental services, and collaborative working. PMID- 26263599 TI - Dentists' knowledge of oral health during pregnancy: a review of the last 10 years' publications. AB - Pregnancy is a period in which several physical and emotional changes occur. These changes in pregnant women's mouths promote changes that need to be known by dentists, so that they can provide the necessary care to women. PURPOSE: To gather data from published studies on the knowledge of dentists about the oral health of pregnant women. METHODS: Papers published between 2003 and 2013 containing surveys on the topic under study were searched. Fourteen studies were selected and grouped into work areas. RESULTS: Dentists have doubts and fears about the care of pregnant women, to a greater or lesser degree, especially with regard to the use of X-rays, prescriptions and ideal gestational period of treatment. CONCLUSION: The results suggest a need to improve dentists' knowledge regarding dental care of pregnant women especially as during pregnancy women may acquire new habits relevant to the oral health of their children. PMID- 26263598 TI - Identifying dentists' attitudes towards prevention guidance using Q-sort methodology. AB - OBJECTIVE: To gain insight into the attitudes and motivating factors of dentists working in the English National Health Service (NHS) towards prevention guidance. DESIGN: Q-methodology: an established hybrid quantitative/qualitative technique used in the social sciences to categorise subjects based on their views by considering factors as part of their overall decision-making profile. SETTING: General Dental Practices offering care under an NHS contract. SUBJECTS AND METHODS: NHS dentists (n = 26) placed 36 statements about prevention guidance derived from an earlier study into a distribution grid that ranked the statements from "most agree" to "most disagree". Principal components factor analysis was applied to determine the principal patterns in the rankings of statements. RESULTS: Analysis indicated a total of six distinct profiles within the responses, of which three profiles had at least six dentists loading onto them. The first profile was strongly characterised by dentists who appear motivated to provide prevention but financial and time constraints prevent them from doing so. The second was characterised by dentists using prevention guidance but restricting its use to only certain patients. The third was characterised by dentists who appeared "health-focused". They placed importance on working to prevention guidance, but were keen to have greater patient and professional support in achieving this. CONCLUSION: In this group of dentists Q-methodology identified three main profiles to the delivery of prevention guidance. PMID- 26263600 TI - A new capitation payment system in dentistry: the patients' perspective. AB - OBJECTIVE: To investigate patients' experiences of a new payment system for dental care in Sweden. METHODS: Twenty interviews, with 12 women and 8 men, were analysed by thematic content analysis. The interviewees were all regularly attending patients, strategically selected from five general Public Dental Service clinics in urban Gothenburg, Sweden, who had chosen a new payment system based on capitation rather than the traditional fee-for-service system. Conducted by two clinical psychologists/researchers independent of dental profession, the interviews were guided by a semi-structured schedule, which included questions about the new payment system and about dental care and oral health. All interviews were audio-recorded and transcribed verbatim. RESULTS: Two themes emerged from the analysis: "Choice" and "Commitment". The sub-themes defined patients as having chosen the new capitation scheme on their own initiative or after being influenced by relatives or by their dentist, and that the change of payment system was occasioned by previous bad (dental) experiences or in the hope of future (dental health) gain. The commitment was perceived as affording economic security and, through the contractual relationship with the provider, regular calls to attend the clinic. CONCLUSIONS: Patients were generally in favour of the new payment system for dentistry in Sweden; however, important arguments were raised to improve the system, such as better communication concerning the contract and risk assessment. PMID- 26263602 TI - Caries experience among Romanian schoolchildren: prevalence and trends 1992-2011. AB - OBJECTIVES: To assess the caries experience of 6-8- and 11-13-year-olds in Romania and to compare their caries levels with those from a previous study conducted in 1992. METHODS: A cross-sectional pathfinder survey was conducted in five major cities of Romania (Iasi, Timisoara, Cluj-Napoca, Tirgu Mures and the capital, Bucharest) in 2011. Cities were purposively chosen for comparability with the 1992 study. Children were clinically examined by one trained dental examiner using the International Caries Detection and Assessment System (ICDAS II). RESULTS: Among the 548 6-8-year-olds, 84.3% had caries experience (82.7% when carious lesions at stages 1-2 were excluded) with mean d1-6mft and d3-6mft of 4.76 (sd 3.46) and 4.43 (sd 3.35) respectively. Among the 592 11-13-year-olds, 83.1% had caries experience (76% when carious lesions at stages 1-2 were excluded) with mean D1-6MFT and D3-6MFT of 4.52 (sd 4.01) and 3.39 (sd 3.35) respectively. Advanced carious lesions were the main contributors to children's caries experience. There were significant differences by cities, with the lowest caries levels seen in Bucharest. High caries levels have persisted in Romania over the last decades in spite of a small but significant decrease in d3-6mft and D3-6MFT values between 1992 and 2011. Variations in caries trends were found by city. CONCLUSION: These findings show that high caries levels still exist among schoolchildren in the five cities included in the study. Romania has not yet achieved the WHO target for 2000 of an average DMFT lower than 3 at 12 years of age. PMID- 26263603 TI - The association between parents' perceived social norms for toothbrushing and the frequency with which they report brushing their child's teeth. AB - OBJECTIVES: To determine whether parents' judgements on how often other parents brush their children's teeth are associated with the frequency with which they brush their own children's teeth, and their satisfaction with their child's brushing routine. METHODS: A cross-sectional questionnaire survey completed by 297 parents of children aged 3-6. Parents were asked how often they brushed their own child's teeth per week, how often they thought other parents did so, and how satisfied they were with their child's toothbrushing routine. Demographic data were also collected. RESULTS: The mean frequency that parents brushed their children's teeth was 12.5 times per week. Multiple regression analysis tested the relationship between parents' perceptions of other parents brushing frequency (mean 10.5 times per week) and how often they brushed their own child's teeth, controlling for socio-demographic factors, and yielded a positive association (p < 0.001). There was a positive association between parents' satisfaction with their child's brushing routine and the extent to which they thought it was better than that of the average child (p < 0.001). CONCLUSIONS: Parents' judgements on how frequently other parents brush their children's teeth are associated with their own behaviour and satisfaction. Re-framing oral health messages to include some form of social normative information ("most parents do this") may prove more persuasive than simple prescriptive advice ("you should do this"). PMID- 26263601 TI - A pilot project to improve the oral health of orphans and of the elderly in residential care in Constanta, Romania. AB - AIM: A pilot project to improve the oral health of Romanian orphans and elderly people in residential homes. MATERIAL AND METHODS: The orphanage and old persons' home were in Constanta. After training, 50 fifth-year dental students made 14 weekly residential home visits to improve carers' oral health knowledge and oral hygiene (OH) procedures and to monitor progress in one orphan and one old person. At baseline and after 14 weeks a local dental school staff member examined each orphan and old person's oral health using WHO (1997) criteria and the Simplified Oral Hygiene Index (OHI-S). The carers' knowledge of OH and attitudes to providing and the students' knowledge and attitudes were assessed at baseline and again after 14 weeks with a questionnaire. RESULTS: All 56 orphans (mean age 9.6 years, mean DMFT 2.39) living in the home participated and their mean OHI-S improved (1.40 to 0.80, p < 0.0001). Fifty old people (mean age 75.9 years) participated, of whom 22 (44%) were edentulous. There was no significant improvement in mean OHI-S (p < 0.10). The carers' oral health knowledge improved (mean scores from 65 to 88, p < 0.001) as did their attitude score (p < 0.013). Students noted changes in their understanding of the needs of the carers, orphans and elderly people. Their perception of their capability to provide OH education or train others to do so, or their inclination to do so remained substantially unchanged. CONCLUSIONS: This pilot study met its aims suggesting that with suitable management, senior dental students can play a significant role in residential homes for orphans and old people by training carers and improving the residents' oral hygiene. Further similar studies in other settings are indicated. PMID- 26263604 TI - Association between dental status and food diversity among older Japanese. AB - OBJECTIVE: To investigate the relationship of dental status to food diversity among older Japanese. DESIGN AND SETTING: A community-based cross-sectional study conducted in the town of Tosa, Kochi Prefecture, Japan. METHODS: The study participants were 252 Japanese (84 men and 168 women, average age 81.2 years) and dentate participants were classified into three groups: 1-9 teeth, 10-19 teeth and 20 or more teeth. Food diversity was assessed as a validated measure of dietary quality using the 11-item Food Diversity Score Kyoto (FDSK-11), which evaluates frequency of consumption of 11 main food groups. Multivariable analysis of the differences in FDSK-11 score ranging from 0 to 11, with a higher score indicating greater food diversity, among the three dental status groups was conducted using general linear models. All the performed analyses were stratified by gender. RESULTS: There was no association between dental status and food diversity score in models for men. In contrast, women with <= 9 teeth and with 10 19 teeth had significantly lower FDSK-11 scores than women with >= 20 teeth after adjusting for confounders (p < 0.001 and p = 0.009, respectively). Additionally, there was a trend toward lower scores for FDSK-11 with fewer teeth (p = 0.001). CONCLUSION: A less varied diet, as indicated by low FDSK-11 score, was observed in female participants with fewer teeth. Tooth loss was associated with poor diet quality among older Japanese women. PMID- 26263607 TI - Your voices and the language of the profession. PMID- 26263606 TI - Human papillomavirus and oral cancer: a primer for dental public health professionals. AB - There is strong evidence for causal association between human papillomavirus (HPV) and cervical cancer, evidence of association of HPV and oropharyngeal cancer is beginning to mount. OBJECTIVES: To review the HPV-oral cancer literature for a comprehensive assessment of the issues involved. METHODS: Literature search conducted using PubMed, Google Scholar and Google search engine. RESULTS: Both available HPV vaccines are efficacious and safe although expensive. Policy for mandatory HPV vaccination for cervical prevention is mired in political issues stemming from negative cost-effectiveness balance. Dental professionals are not ready to discuss the role of HPV vaccine in cancer prevention. This review discusses the impact of HPV on cervical cancer, transmission of HPV among humans, impact of HPV in oral health, and its plausible role in oral and oropharyngeal cancer, prevention of HPV transmission, available vaccines against HPV, testing, cost, policy and use of HPV vaccines internationally and dentists readiness related to HPV associated health communication. CONCLUSIONS: Given the mounting literature on the association between HPV and oropharyngeal cancer, the dental community must be prepared to answer patients' HPV-related questions and to educate patients about the role of HPV as a risk factor for oral and oropharyngeal cancers. PMID- 26263608 TI - Part of the bigger picture. PMID- 26263605 TI - Are Stage of Change constructs relevant for subjective oral health in a vulnerable population? AB - Stage of Change constructs may be proxy markers of psychosocial health which, in turn, are related to oral health. OBJECTIVE: To determine if Stage of Change constructs were associated with subjective oral health in a population at heightened risk of dental disease. METHODS: Stage of Change constructs were developed from a validated 18-item scale and categorised into 'Pre contemplative', 'Contemplative' and 'Active'. A convenience sample of 446 Australian non-Aboriginal women pregnant by an Aboriginal male (age range 14-43 years) provided data to evaluate the outcome variables (self-rated oral health and oral health impairment), the Stage of Change constructs and socio demographic, behavioural and access-related factors. Factors significant at the p < 0.05 level in bivariate analysis were entered into prevalence regression models. RESULTS: Approximately 54% of participants had fair/poor self-rated oral health and 34% had oral health impairment. Around 12% were 'Pre-contemplative', 46% 'Contemplative' and 42% 'Active'. Being either 'pre-contemplative' or 'contemplative' was associated with poor self-rated oral health after adjusting for socio-demographic factors. 'Pre-contemplative' ceased being significant after adjusting for dentate status and dental behaviour. 'Pre-contemplative' remained significant when adjusting for dental cost, but not 'Contemplative'. The Stages of Change constructs ceased being associated with self-rated oral health after adjusting for all confounders. Only 'Contemplative' (reference: 'Active') was a risk indicator in the null model for oral health impairment which persisted after adding dentate status, dental behaviour and dental cost variables, but not socio demographics. When adjusting for all confounders, 'Contemplative' was not a risk indicator for oral health impairment. CONCLUSIONS: Both the 'Pre-contemplative' and 'Contemplative' Stage of Change constructs were associated with poor self rated oral health and oral health impairment after adjusting for some, but not all, covariates. When considered as a proxy marker of psychosocial health, Stage of Change constructs may have some relevance for subjective oral health. PMID- 26263609 TI - Number needed to treat in RCTs. PMID- 26263610 TI - Communicating with people with dementia: Avoiding mistakes. PMID- 26263611 TI - Military metaphors have outlived their usefulness. PMID- 26263612 TI - Primary health care in action. PMID- 26263614 TI - Town halls focus on home health care. PMID- 26263613 TI - Nurses, MPs abuzz during National Nursing Week. PMID- 26263615 TI - Advocacy in action for the NP role. PMID- 26263616 TI - Learning to Use an EHR: Nurses's stories. PMID- 26263617 TI - Stepping into her comfort zone. PMID- 26263618 TI - Speaking up: What are you waiting for? PMID- 26263619 TI - [Cyanobacterial Phycobilisomes and Phycobiliproteins]. AB - In cyanobacteria, phycobilisomes (PBS) act as antennae of the photosynthetic pigment apparatus. They contain brightly colored phycobiliproteins (PBP) and form giant supramolecular complexes (up to 3000-7000 kDa) containing 200 to 500 phycobilin chromophores covalently bound to the proteins. Over ten various PBP are known, which fall into three groups: phycoerythrins, phycocyanins, and allophycocyanins. Hollow disks of PBP trimers and hexamers are arranged into cylinders by colorless linker proteins; the cylinders are then assembled into PBS. Typical semidiscoid PBS consist of a central nucleus formed by three allophycocyanin cylinders and of six lateral cylinders consisting of other PBP and attached as fans to the nucleus. The PBS number, size, and pigment composition in cyanobacteria depend on illumination and other ambient factors. While PBS have certain advantages compared to other antennae, these pigment protein complexes require more energy than the chlorophyll a/b- and chlorophyll a/c-proteins of oxygenic photosynthetic organisms. PMID- 26263620 TI - [CO2-Concentrating Mechanism and Its Traits in Haloalkaliphilic Cyanobacteria]. AB - Cyanobacteria are a group of oxygenic phototrophs existing for at least 3.5 Ga. Photosynthetic CO2 assimilation by cyanobacteria occurs via the Calvin cycle, with RuBisCO, its key enzyme, having very low affinity to CO2. This is due to the fact that atmospheric CO2 concentration in Archaean, when the photosynthetic apparatus evolved, was several orders higher than now. Later, in the epoch of Precambrian microbial communities, CO2 content in the atmosphere decreased drastically. Thus, present-day phototrophs, including cyanobacteria, require adaptive mechanisms for efficient photosynthesis. In cyanobacterial cells, this function is performed by the CO2-concentrating mechanism (CCM), which creates elevated CO2 concentrations in the vicinity of RuBisCO active centers, thus significantly increasing the rate of CO2 fixation in the Calvin cycle. CCM has been previously studied only for freshwater and marine cyanobacteria. We were the first to investigate CCM in haloalkaliphilic cyanobacteria from soda lakes. Extremophilic haloalkaliphilic cyanobacteria were shown to possess a well developed CCM with the structure and functional principles similar to those of freshwater and marine strains. Analysis of available data suggests that regulation of the amount of inorganic carbon transported into the cell is probably the general CCM function under these conditions. PMID- 26263621 TI - [Invertase Overproduction May Provide for Inulin Fermentation by Selection Strains of Saccharomyces cerevisiae]. AB - In some recent publications, the ability of selection strains of Saccharomyces cerevisiae to ferment inulin was attributed to inulinase activity. The review summarizes the literature data indicating that overproduction of invertase, an enzyme common to S. cerevisiae, may be responsible for this phenomenon. PMID- 26263622 TI - [Diversity of Cuproproteins and Copper Homeostasis Systems in Melioribacter roseus, a Facultatively Anaerobic Thermophilic Member of a New Phylum Ignavibacteriae]. AB - The genome of Melioribacter roseus, one of two members of the recently described phylum Ignavibacteriae, was searched for the genes encoding proteins associated with copper transport or containing copper as cofactors, and the effect of Cu2+ concentration in the medium on M. roseus growth was investigated. Genomic analysis revealed a variety of copper-containing oxidoreductases in this facultative anaerobe. Three ATPases responsible for copper transport were identified. One of them (MROS_1511) was.probably involved in assembly of the copper-containing cytochrome c oxidase, while two others (MROS_0327 and MROS_0791) probably carried out a detoxification function. The presence of several copper-containing oxidoreductases and copper homeostasis systems in M. roseus is in agreement with the previously hypothesized origin of the phylum Ignavibacteriae from an aerobic ancestor common with those of Bacteroidetes and Chlorobi. PMID- 26263623 TI - [Biofilm Formation by the Nonflagellated flhB1 Mutant of Azospirillum brasilense Sp245]. AB - Azospirillum brasilense Sp245 with mixed flagellation are able to form biofilms on various surfaces. A nonflagellated mutant of this strain with inactivated chromosomal copy of the flhB gene (flhB1) was shown to exhibit specific traits at the later stages of biofilm formation on a hydrophilic (glass) surface. Mature biofilms of the flhB1::Omegon-Km mutant Sp245.1063 were considerably thinner than those of the parent strain Sp245. The biofilms of the mutant were more susceptible to the forces of hydrodynamic shear. A. brasilense Sp245 cells in biofilms were not found to possess lateral flagella. Cells with polar flagella were, however, revealed by atomic force microscopy of mature native biofilms of strain Sp245. Preservation of a polar flagellum (probably nonmotile) on the cells of A. brasilense Sp245 may enhance the biofilm stability. PMID- 26263624 TI - [Stress Resistance Mechanisms in the Indicator Fungi from Highly Radioactive Chernobyl Zone Sites]. AB - Comparison of the levels of the protein carboxylic groups in response to peroxide stress revealed enhanced stress resistance in Purpureocillium lilacinum strains isolated from soils with high content of copper or radionuclides compared to the strains isolated from uncontaminated soils. While in background strains resistance to peroxide stress increased with glucose content in the medium increasing from 0.002 to 2%, the strains from radionuclides- or copper contaminated soils did not exhibit this pattern. Respiratory activity and polyphosphate content were compared for radiation-resistant strain 1941 and strain SM from the area with zero radioactivity. For the protoplasts of strain 1941 isolated from the Chernobyl zone, elevated respiratory activity was revealed on the media with low glucose content. Under the control conditions, the content of inorganic polyphosphates (polyP) in strains 1941 and SM was the same. Under conditions of peroxide stress, only the background strain SM grown on the medium with low glucose concentration exhibited decreased levels of inorganic polyphosphates. Independent on glucose concentration in the medium, in both P. lilacinum strains, polyP content increased in the course of regeneration after peroxide stress. PMID- 26263625 TI - [Hybrid Sterility of the Yeast Schizosaccharomyces pombe: Genetic Genus and Many Species in statu nascendi?]. AB - A phenomenon of ascospore death was observed in a number of Schizosaccharomyces pombe interstrain hybrids. Meiotic recombination of the control parental auxotrophic markers was, however, observed in a random ascospore analysis. Genetic and molecular biological data indicated existence of at least geographical divergence of the genomes in Sch. pombe populations. Classification of the genus, species, and varieties of these yeasts is discussed. PMID- 26263627 TI - [Intraspecific and Intrageneric Antagonistic Activity of Wickerhamomyces anomalus]. AB - A total of 53 Wickerhamomyces anomalus strains were examined for antagonistic activity, including the nomenclature types of the species with the names presently considered synonymous. Over 70% of the strains exhibited antibiotic activity. According to the action spectra of intraspecific activity, the strains fell into three groups, while according to their activity against other Wickerhamomyces species and phylogenetically related Candida species they formed five subgroups. Antibiotic agents (mostly mycocins) varied in their physicochemical properties. PMID- 26263626 TI - [Lipid Composition in Cell Walls and in Mycelial and Spore Cells of Mycelial Fungi]. AB - Qualitative and quantitative differences were found between the lipids of cell walls (CW) and of whole mycelial cells and dormant cells of mucoraceous and ascomycete fungi. Thus, whole mycelial cells (WC) contained more lipids than CW. Unlike sporangiospores and conidia (exogenous dormant spores), zygotes were found to have the highest content of triacylglycerol lipids (70%). Cell walls of mucoraceous fungi contained more triacylglycerols (TAG) and less polar lipids than ascomycete lipids. While all CW and WC studied were similar in fatty acid (FA) composition, their ratio was specific for each structure: linoleic acid predominated in mycelial CW and WC, while oleic acid was predominant in the spores; this difference was especially pronounced in conidial WC. Unlike WC, in CW massive lipids may be represented not by phosphatidylethanolamine (PEA) and phosphatidylcholine (PC), but by free fatty acids (FFA), free (FSt) and etherified sterols (ESt), phosphatidic acid (PA), fatty acid methyl esters (FAME), and glycolipids (GL), which is an indication of a special functional role of CW. PMID- 26263628 TI - [Leaching of Rare Earth Elements from Coal Ashes Using Acidophilic Chemolithotrophic Microbial Communities]. AB - A method for leaching rare earth elements from coal ash in the presence of elemental sulfur using communities of acidophilic chemolithotrophic microorganisms was proposed. The optimal parameters determined for rare element leaching in reactors were as follows: temperature, 45 degrees C; initial pH, 2.0; pulp density, 10%; and the coal ash to elemental sulfur ratio, 10 : 1. After ten days of leaching, 52.0, 52.6, and 59.5% of scandium, yttrium, and lanthanum, respectively, were recovered. PMID- 26263629 TI - [Rhodobaculum claviforme gen. nov., sp. nov., a New Alkaliphilic Nonsulfur Purple Bacterium]. AB - Two alkaliphilic strains of nonsulfur purple bacteria (NPB), B7-4 and B8-2, were isolated from southeast Siberia moderately saline alkaline steppe lakes with pH values above 9.0. The isolates were motile, polymorphous cells (from short rods to long spindly cells) 2.0-3.2 x 9.6-20.0 MUm. Intracellular membranes of vesicular type were mostly located at the cell periphery. The microorganisms contained bacteriochlorophyll a and carotenoids of the spheroidene and spirilloxanthin series. The photosynthetic apparatus was represented by LH2 and LH1 light-harvesting complexes. In the presence of organic compounds, the strains grew aerobically in the dark or anaerobically in the light. Capacity for photo- and chemoautotrophic growth was not detected. The cbbl gene encoding RuBisCO was not revealed. Optimal growth of both strains occurred at 2% NaCl (range from 0.5 to 4%), pH 8.0-8.8 (range from 7.5 to 9.7), and 25-35 degrees C. The DNA G+C content was 67.6-69.8 mol %. Pairwise comparison of the nucleotides of the 16S rRNA genes revealed that strains B7-4 and B8-2 belonged to the same species (99.9% homology) and were most closely related to the aerobic alkaliphilic bacteriochlorophyll a-containing anoxygenic phototrophic bacterium (APB) Roseibacula alcaliphilum De (95.2%) and to NPB strains Rhodobaca barguzinensis VKM B-2406(T) (94.2%) and Rbc. bogoriensis LBB1(T) (93.9%). The isolates were closely related to the NPB Rhodobacter veldkampii DSM 11550(T) (94.8%) and to aerobic bacteriochlorophyll a-containing bacteria Roseinatronobacter monicus ROS 35(T) and Roseicitreum antarcticul ZS2-28(T) (93.5 and 93.9%, respectively). New strains were described as a new NPB genus and species of the family Rhodobacteriaceae, Rhodobaculum claviforme gen. nov., sp. nov., with B7-4(T) (VKM B-2708, LMG 28126) as the type strain. PMID- 26263630 TI - [Candidatus "Jettenia moscovienalis" sp. nov., a New Species of Bacteria Carrying out Anaerobic Ammonium Oxidation]. AB - A new species of bacteria oxidizing ammonium with nitrite under anoxic conditions was isolated from the activated sludge of a semi-industrial bioreactor treating digested sludge of the Kuryanovo wastewater treatment plant (Moscow, Russia). Physiological, morphological, and molecular genetic characterization of the isolate was carried out. The cells were ovoid (-0.5 x 0.8 MUm), with the intracellular membrane structures characteristic of anammox bacteria (anammoxosome and paryphoplasm); unlike other anammox bacteria, it possessed extensive intracellular membrane structures located in layers parallel to the cytoplasmic membrane, but never close to the anammoxosome. The cells formed aggregates 5-28 MUm in diameter and readily attached to solid surfaces. The cells were morphologically labile, easily plasmolyzed, and lost their content. Doubling time was 28 days, MU(max) = 0.025 day(-1); optimal temperature and pH for growth were 20-45 degrees C and 8.0, respectively. Phylogenetic analysis of the 16S rRNA gene sequences suggested its classification as a new species of the candidate genus Jettenia (order Planctomycetales). The name Candidatus "Jettenia moscovienalis" sp. nov. was proposed for the new bacterium. PMID- 26263631 TI - [Immunochemical Detection of Azospirilla in Soil with Genus-Specific Antibodies]. AB - Immunoelectrophoresis and immunodiffusion analysis with antibodies to whole intact cells of the type strain of nitrogen-fixing soil bacteria Azospirillum brasilense Sp7 revealed at least three conservative surface immunogenic proteins of azospirilla. Cross-reactions with these proteins made it possible to use the above antibodies for detection of azospirilla as a genus-specific probe conjugated with horseradish peroxidase as an enzymatic label. Direct immune enzyme analysis of soil suspensions (typical chernozem, Saratov oblast) confirmed applicability of the conjugates based on genus-specific antibodies to the surface proteins of azospirilla for direct detection of this bacterial genus in environmental samples. These results provide a basis for broad application of this method for analysis of Azospirillum occurrence in soil. PMID- 26263632 TI - [Sulfate-Reducing Bacterial Communities in the Water Column of the Gdansk Deep (Baltic Sea)]. AB - Biodiversity of sulfate-reducing bacterial communities in the water column of the Gdansk Deep, Baltic Sea, where H2S had been detected in near-bottom layers, was analyzed by PCR with primers for the 16S rRNA genes of six major phylogenetic subgroups of sulfate-reducing bacteria (SRB). Using denaturing gradient gel electrophoresis followed by sequencing, the nucleotide sequences of reamplified dsrB gene fragments from investigated water samples were determined. For the first time the presence of nucleotide sequences of the dsrB gene was detected by PCR in the water samples from all hydrochemical layers, including subsurface oxic waters. The presence of the 16S rRNA genes of representatives of Desulfotomaculum, Desulfococcus-Desulfonema-Desulfosarcina, and Desulfovibrio Desulfomicrobium SRB subgroups was also revealed throughout the water column of the Gdansk Deep. Analysis of translated amino acid sequences encoded by the dsrB gene demonstrated the highest homology with the relevant sequences of uncultured SRB from various marine habitats. PMID- 26263633 TI - [ROENTGEN-ENDOVASCULAR EMBOLIZATION OF THE PORTAL VEIN BRANCHES AS A PATIENTS CONDITIONING FOR EXTENSIVE HEPATIC RESECTION]. AB - The results of surgical treatment of 316 patients, suffering focal hepatic diseases, in whom for preoperative preparation a portal vein embolization (PVE) was performed, were analyzed. PVE was applied in a small planned hepatic residual volume. The patients have aged from 21 to 77 yrs, (57 +/- 10.6) yrs at average. During (22 +/- 7) days after the procedure a hypertrophy of a planned postresectional hepatic volume by 58.6% was observed, while a hypertrophy degree have depended on the embolization volume performed: 57.3%--after embolization of branches of C(V)-C(VIII) hepatic segments, 66%--the segments C(V)-C(VIII) + C(IV). In 281 (89%) patients the extensive hepatic resection was performed, a fatal postresection hepatic insufficiency was not observed. A three-year and five year disease-free survival have constituted 43.8 and 16.4% accordingly. Thus, a PVE constitutes a miniinvasive intervention, permitting to achieve a planned residual hepatic volume, to expand a diapazon of application of radical extensive hepatic resection in patients, suffering focal hepatic diseases while a small planned residual hepatic volume. PMID- 26263634 TI - [SURGICAL TREATMENT OF TUMORS OF THE LEFT PANCREATIC ANATOMICAL SEGMENT]. AB - The results of treatment of 231 patients, suffering tumoral affection of pancreatic left anatomical segment in period of 2009-2013 yrs were analyzed. Individualized approach, using modern technologies, was applied. Radical operations were performed in 129 patients, ageing 14-81 yrs old, including pancreatic distal resections in various modifications, central resection and tumoral enucleation. Possibilities of the extended pancreatic resection performance were studied in conditions of tumoral invasion of adjacent organs, regional vessels, as well as impact of such interventions on postoperative complications and lethality rate. While performing pancreatic subtotal distal resection with simultant resection of affected main venous vessels and adjacent organs the operative intervention risk is enhanced, but possibilities of a radical operations performance in previously considered inoperable patients are expanding. PMID- 26263635 TI - [DYNAMICS OF CHANGES OF PROINFLAMMATORY AND ANTIINFLAMMATORY CYTOKINES, AS WELL AS SOME INDICES OF THE BLOOD PEROXIDATION SYSTEM, IN THE PATIENTS WITH VARIOUS PANCREATIC PSEUDOCYST TYPES]. AB - The investigation was performed in 47 patients, operated on for pancreatic pseudocysts (PP). The PP type was established in accordance to A. D'Egidio, M. Schein (1991) classification. The blood plasma contents of proinflammatory and antiinflammatory cytokines, including interleukins (IL): IL-6, IL-8, IL-10, IL 18, as well as malonic dialdehyde and activity of glutationperoxidase, were determined for estimation of the immune state disorders. Mostly expressed changes in IL-8 content were registered in complicated PP in 72 h postoperatively, what was have characterized by more expressed raising of its level in systemic blood flow, than in a splanchnic one, in all types of PP and witnessed a hepatic capacity to guarantee a cytokine's clearance in all the patients. The contents of glutationperoxidase and IL-18 in the blood serum in various types of PP have correlated immediately with pancreatitis severity. Close correlative connection between these indices while unfavorable prognosis of postoperative period course was established. PMID- 26263636 TI - [IMMUNOLOGICAL FACTORS OF THE INNATE IMMUNITY IN PATIENTS WITH HEPATOCELLULAR CARCINOMA OF A LARGE SIZE]. AB - Factors of the inborn immunity in patients, suffering hepatocellular carcinoma of large size, were studied. Preoperatively the raising of metabolic activity of neutrophils in spontaneous NST-test, the neutrophils reserve reduction in NST test, weak activation of the neutrophils absorption function in a phagocytosis reaction were noted. On the 7-8th postoperative day a reduction of quantity of formazan--positive neutrophils in spontaneous NST--test, raising of reserve of the neutrophils metabolic activity, comparing with initial values, were observed. PMID- 26263637 TI - [SURGICAL TREATMENT OUTCOME IN PATIENTS WITH COLORECTAL CANCER AND CONCOMITANT LIVER METASTASES]. AB - Colorectal cancer with synchronous liver metastasis (sm-CRC) is extremely unfavorable prognostic factor. Surgery remains is most effective method, able to extend the life of these patients. The results of treatment of 126 patients with sm-CRC were analyzed, whom performed simultaneous (group I) or staged (group II) surgery. Simultaneous resection of 3 segments of liver or less with metastases and primary tumor is a safe surgical strategy (complicatios level was 4.8%); simultaneous resection of 3 segments of liver or more increase the complicatios level to 20.9%. Simultaneous resection ensure reduction of hospital stay terms in 58.1% and duration of surgery in 71.3% (p < 0.001). The average cost of treatment patient treating with staged strategy exceeded in simultaneous surgical treatment in 40.9%. PMID- 26263638 TI - [TREATMENT MODALITIES OF THE FOREGUT HEMORRHAGES WHILE PERFORMING ENDOSCOPIC MONITORING]. AB - Complex clinical examination was done in 107 patients, in whom gastrointestinal hemorrhage (GIH) of various etiology, have had occurred. Special attention was drawn toward early conduction of esophagogastroduodenofibroscopy, as a leading instrumental method, permitting to reveal a GIH source, its character and degree of hemostasis in accordance to J. Forrest scale. The patients state severity while hemorrhage from the foregut presence was estimated in accordance to routine principles, depending on the circulating blood volume deficiency. The structure algorithm for the patients' management, in accordance to which treatment tactic must be selected individually, permitting to improve the quality of the medical help delivery for the patients, was elaborated. PMID- 26263639 TI - [IMPACT OF OPERATIVE INTERVENTION ON DYNAMICS OF THE IMMUNITY INDICES IN AN ACUTE GASTRODUODENAL HEMORRHAGE]. AB - The results of surgical treatment of 39 patients, suffering an acute gastroduodenal ulcer hemorrhage, were analyzed. Gastric ulcer disease was diagnosed in 9 patients, duodenal ulcer disease--in 29, combined ulcer--in 1. A light degree blood loss was noted in 13 patients, while a middle degree--in 12, and severe--in 14. In accordance to J. Forrest classification in 6 patients an active bleeding was revealed (FIa, FIb), in 11--nonstable hemostasis (FIIa, FIIb, FIIc), and in 22--FIII. Preoperatively in patients on the third, seventh and fourteenth day the contents of CD3+, CD4+, CD8+, CD19, calculation of a CD4+/CD8+ ratio, the level of immunoglobulins (IgA, IgM, IgG) and circulating immune complexes were determined in peripheral blood. Phagocytic activity of neutrophils was estimated, using determination of phagocytic index and phagocytic number. In an acute gastroduodenal ulcer hemorrhage immunosuppression was noted, and severity of disorders in T- and B-chains of immunity have depended upon a blood loss severity. Conduction of a routine basic conservative therapy in postoperative period did not guarantee elimination of immunosuppression. PMID- 26263640 TI - [THE WAYS FOR IMPROVEMENT OF PERITONITIS TREATMENT OUTCOMES AT A MODERN TIME]. AB - The results of treatment of 53 patients, suffering extended peritonitis, were analyzed. Application of differentiated surgical tactics, the least traumatic volume of operative intervention for the patient, determination of indications for relaparotomy and secondary videolaparoscopic sanation, taking into account data on ultrasonic monitoring of abdominal organs, optimization of the inserted draining tubes quantity, depending on source and severity of peritonitis on background of early enteral feeding accomplished, have permitted to improve the patients treatment results, to reduce a postoperative complications and lethality rate. PMID- 26263641 TI - [CLINICO-EXPERIMENTAL SUBSTANTIATION OF INTRAABDOMINAL PLASTY FOR UMBILICAL HERNIAS]. AB - The impact of various methods of plasty, using net implants, on results of umbilical hernias treatment was studied in experimental and clinical investigation. The umbilical hernias plasty was performed in accordance to the IPOM (intraperitoneal on lay mesh) method, application of which have permitted to reduce a hospital stay of the patients as well as their period of social rehabilitation, and to guarantee the best cosmetic effect in comparison with such while making umbilical hernias plasty in accordance to a sub lay method. PMID- 26263642 TI - [DEFORMITY OF LEFT VENTRICLE WALLS IN PATIENTS WITH AORTAL VALVE STENOSIS]. AB - Parameters of longitudinal deformity of left ventricle walls in patients, suffering aortal valve stenosis (AVS), were analyzed. While the process of heart contraction in norm and in AVS occurs, longitudinal deformity is expressed maximally in its apical divisions. AVS deformity of apical divisions of left ventricle, as well as middle divisions of interventricular septum and lower wall, practically did not differ from such in norm, and deformity of basal divisions of all walls and middle divisions of posterior, lateral and anterior walls of left ventricle was trustworthy less than a norm. Thus, a reduction of the deformity indices in basal divisions of left ventricle and middle segments of its posterior, lateral and anterior walls in patients, suffering AVS with preserved output fraction, precedes the disorders of its hemodynamics and constitutes a predictor for the cardiac output reduction. PMID- 26263643 TI - [APPLICATION OF LARGE SUBCUTANEOUS VEIN AS MATERIAL FOR DISTAL SHUNTING IN CRITICAL ISCHEMIA OF THE LOWER EXTREMITY TISSUES]. AB - While performing autologous reconstruction of distal arteries in 24 patients in chronic critical ischemia of the lower extremity tissues the method of a large subcutaneous vein mobilization, using a ring-like desobliterator,was applied. This have permitted to reduce the procedure traumaticity, comparing with a standard method. Additional application of pharmacological vasodilatation of venous transplant have permitted to avoid the risk, connected with impact of hydraulic vasodilatation on the venous wall functional state. PMID- 26263644 TI - [AMPUTATION OR EXARTICULATION OF TOES IN PATIENTS WITH DIABETIC FOOT SYNDROME]. AB - The results of surgical treatment of 127 patients, suffering diabetic foot syndrome, were analyzed. In 82 patients (1st group) a radical toe extirpation was accomplished; in 45 (2nd group)--a phalangopreserving operations (amputaion of toe, necrectomy, sequestrectomy, the abscess opening) were done. The reoperation rate in patients of the 1st group have constituted 6.1%, the wound suppuration 3.6%, in a 2nd group satisfactory results were achieved in 26.7% of patients, and in the rest of them--reoperations were done for the pathological process progression. PMID- 26263645 TI - [CHARACTERIZATION OF VESTIBULAR DISORDERS IN THE INJURED PERSONS WITH THE BRAIN CONCUSSION IN ACUTE PERIOD]. AB - There were examined 32 injured persons, ageing (34.1 +/- 1.3) yrs at average, for the brain commotion (BC). The adopted protocol SCAT-3 (Standardized Concussion Assessment Tool, 3rd ed.), DHI (Dizziness Handicap Inventory questionnaire), computer stabilography (KS) were applied for the vestibular disorders diagnosis. There was established, that in acute period of BC a dyssociation between regression of objective neurological symptoms and permanence of the BC indices occurs, what confirms a latent disorder of the balance function. Changes of basic indices of statokinesiography, including increase of the vibration amplitude enhancement in general centre of pressure in a saggital square and the BC square (235.3 +/- 13.7) mm2 in a modified functional test of Romberg with the closed eyes is possible to apply as objective criteria for the BC diagnosis. PMID- 26263646 TI - [MODIFIED SURGICAL TREATMENT OF PATIENTS WITH PRIMARY OPEN-ANGLE GLAUCOMA]. AB - A combined phacoemulsification of a cataract with intraocular lens implantation (IOLI) and modified tunnel trabeculopuncture (TTP) was performed in the clinic in patients, suffering primary open-angle glaucoma. Through 3 yrs postoperatively intraocular pressure and a glaucoma compensation degree were controlled in accordance to data, obtained while investigation of optic nerve (computer perimetry, optical coherent tomography of neuronal fascicles), and also these results were compared with data from the patients, to whom a standard TTP was performed. A significant stable hypotensive effect of the operation proposed was established, as well as termination of a progressive atrophic changes of optic nerve, caused by glaucoma. Antiglaucomal reoperations after a combined phacoemulsification IOLI and modified TTP were per- formed in 6% patients (p < 0.05), after combined phacoemulsification with the IOLI and a standard TTP--in 30% (p < 0.05). PMID- 26263647 TI - [CYSTIC TUMORS OF SUPRARENAL GLANDS AND PECULIARITIES OF ITS SURGICAL TREATMENT]. AB - The clinic experience for surgical treatment of patients, suffering cyst of suprarenal gland (SG), consisted of laparoscopic resection of SG together with a cyst and preserving a visually nonaffected parts of SG, due to what the risk reduction for chronic suprarenal insufficiency of various degree occurrence was achieved. The proposed method was applied in 49 (86.0%) patients of 57, who were operated on for the SG cysts. Intraoperative morbidity, complicated postoperative course and the recurrence occurrence after the SG resection were not observed. All the patients have had recovered, so application of restorational therapy was not needed. The proposed method of laparoscopic resection of SG together with a cyst, using modern instrumental methods of hemostasis (ultrasonic scissors), permits to avoid excessive resection of functioning parenchyma of SG, to reduce the risk for health and life of the patients, caused by chronic suprarenal insufficiency and intraoperative bleeding. PMID- 26263648 TI - [ABDOMINAL TRANSDIAPHRAGMATIC EXTRAPERICARDIAL SURGICAL ACCESS TO SUPRADIAPHRAGMATIC PART OF VENA CAVA INFERIOR IN PATIENTS OPERATED FOR RENAL-CELL CANCER]. AB - Safety and possibility to perform abdominal surgical accesses to supradiaphragmatic part of vena cava inferior (VCI) in patients, operated on for renal-cell cancer, were estimated. In 12 patients the results of application of several surgical access variants to supradiaphragmatic part of VCI were estimated. Most simple and safe way to isolate supradiaphragmatic VCI and cavaatrial junction is to perform a T-like diaphragmotomy. Intraoperative complications rate have constituted 36.4%. The blood loss volume due to VCI injury (in 3 cases) while performing transdiaphragmatic surgical access to supradiaphragmatic part of VCI, have constituted 112.5 ml at average. Injuries of pleura, pericardium, main truncus of diaphragmatic nerve did not occur. PMID- 26263649 TI - [SURGICAL TREATMENT OF THE INJURED PERSONS WITH SPLENIC TRAUMA IN THE CLOSED COMBINED ABDOMINAL TRAUMA]. AB - The results of treatment of the injured persons, suffering splenic injury, in closed com- bined abdominal trauma, depending on its severity and the splenic injury degree, are presented. PMID- 26263650 TI - [THERMOMETRY APPLICATION FOR ESTIMATION OF THE SKIN BURNS DEPTH]. AB - Determination of the burn wound depth, using noncontact infrared thermometry, permits to predict the burn affection severity, basing on the revealed difference between local, perifocal temperature and temperature in certain nonaffected areas of the body surface. The temperature difference (DeltaT) over 1 degrees C constitutes a strict criterion of the skin burn presence. The temperature 34 degrees C have been considered a border one for the skin burns. If the burn wound temperature in 24 h after trauma was lower 34 degrees C and DeltaT 2 degrees C and more, it have witnessed the presence of deep burn of the skin. High sensitivity (87%) and specificity (96%) of thermometric test in 24 h after trauma were established. In epidermal burns the temperature of the burn wounds have constituted (35.9 +/- 0.3) degrees C at average, in superficial burns of the skin--(35.1 +/- 0.6) degrees C, and in the deep burns--(33.6 +/- 0.8) degrees C. PMID- 26263652 TI - [PROPHYLAXIS OF PARACOLOSTOMIC COMPLICATIONS OF PATIENTS ON TREATMENT FOR ACUTE OBTURATION ILEUS]. PMID- 26263651 TI - [DIVERTICULAR DISEASE OF LARGE BOWEL: DIAGNOSIS, SURGICAL TACTICS]. PMID- 26263653 TI - [RECURRENT HEMORRHANGE FROM MECKEL'S DIVERTICULUM]. PMID- 26263654 TI - [Nikolay Nikolayevich Veligotskiy]. PMID- 26263655 TI - [Mykhaylo Grygorovych Shevchuk]. PMID- 26263656 TI - Understanding protected area resilience: a multi-scale, social-ecological approach. AB - Protected areas (PAs) remain central to the conservation of biodiversity. Classical PAs were conceived as areas that would be set aside to maintain a natural state with minimal human influence. However, global environmental change and growing cross-scale anthropogenic influences mean that PAs can no longer be thought of as ecological islands that function independently of the broader social-ecological system in which they are located. For PAs to be resilient (and to contribute to broader social-ecological resilience), they must be able to adapt to changing social and ecological conditions over time in a way that supports the long-term persistence of populations, communities, and ecosystems of conservation concern. We extend Ostrom's social-ecological systems framework to consider the long-term persistence of PAs, as a form of land use embedded in social-ecological systems, with important cross-scale feedbacks. Most notably, we highlight the cross-scale influences and feedbacks on PAs that exist from the local to the global scale, contextualizing PAs within multi-scale social ecological functional landscapes. Such functional landscapes are integral to understand and manage individual PAs for long-term sustainability. We illustrate our conceptual contribution with three case studies that highlight cross-scale feedbacks and social-ecological interactions in the functioning of PAs and in relation to regional resilience. Our analysis suggests that while ecological, economic, and social processes are often directly relevant to PAs at finer scales, at broader scales, the dominant processes that shape and alter PA resilience are primarily social and economic. PMID- 26263657 TI - Determining origin in a migratory marine vertebrate: a novel method to integrate stable isotopes and satellite tracking. AB - Stable isotope analysis is a useful tool to track animal movements in both terrestrial and marine environments. These intrinsic markers are assimilated through the diet and may exhibit spatial gradients as a result of biogeochemical processes at the base of the food web. In the marine environment, maps to predict the spatial distribution of stable isotopes are limited, and thus determining geographic origin has been reliant upon integrating satellite telemetry and stable isotope data. Migratory sea turtles regularly move between foraging and reproductive areas. Whereas most nesting populations can be easily accessed and regularly monitored, little is known about the demographic trends in foraging populations. The purpose of the present study was to examine migration patterns of loggerhead nesting aggregations in the Gulf of Mexico (GoM), where sea turtles have been historically understudied. Two methods of geographic assignment using stable isotope values in known-origin samples from satellite telemetry were compared: (1) a nominal approach through discriminant analysis and (2) a novel continuous-surface approach using bivariate carbon and nitrogen isoscapes (isotopic landscapes) developed for this study. Tissue samples for stable isotope analysis were obtained from 60 satellite-tracked individuals at five nesting beaches within the GoM. Both methodological approaches for assignment resulted in high accuracy of foraging area determination, though each has advantages and disadvantages. The nominal approach is more appropriate when defined boundaries are necessary, but up to 42% of the individuals could not be considered in this approach. All individuals can be included in the continuous-surface approach, and individual results can be aggregated to identify geographic hotspots of foraging area use, though the accuracy rate was lower than nominal assignment. The methodological validation provides a foundation for future sea turtle studies in the region to inexpensively determine geographic origin for large numbers of untracked individuals. Regular monitoring of sea turtle nesting aggregations with stable isotope sampling can be used to fill critical data gaps regarding habitat use and migration patterns. Probabilistic assignment to origin with isoscapes has not been previously used in the marine environment, but the methods presented here could also be applied to other migratory marine species. PMID- 26263658 TI - Migratory connectivity of a Neotropical migratory songbird revealed by archival light-level geolocators. AB - Understanding migratory connectivity is critical for interpreting population dynamics, seasonal interactions, and for the implementation of conservation strategies of migratory species. We evaluated the migratory connectivity of a Neotropical migratory songbird, the Ovenbird (Seiurus aurocapilla) using archival light-level geolocators deployed at two breeding and four nonbreeding locations while incorporating Ovenbird abundance as prior information using Bayes' Rule. We also included band recoveries submitted to the United States Geological Survey's Bird Banding Laboratory to assess connectivity of areas where geolocators were not deployed. We created a probabilistic map of origin for each capture site and mapped spring migration routes between nonbreeding and breeding locations. We found a complete separation of eastern and western populations of Ovenbirds throughout the annual cycle. Breeding Ovenbirds from western Canada spent the nonbreeding season throughout Central America and migrated through central North America during spring migration. Birds breeding in the northeastern United States were distributed throughout the central Greater Antilles in the Caribbean and migrated through eastern North America during spring migration. Fall migration routes were not included because the timing of migration coincided with fall equinox when latitudinal estimates are unreliable. However, longitudinal estimates suggest no overlap between eastern and western populations during fall migration. Ovenbirds with geolocators attached in Jamaica bred in the northeastern United States with the highest posterior probability of origin found in Massachusetts, while Ovenbirds captured in Florida and Puerto Rico bred primarily in the mid-Atlantic. Incorporating Ovenbird abundance as a prior into geolocator estimates decreased the area of origin by 90.37% +/- 1.05% (mean +/- SE) for the breeding season and 62.30% +/- 1.69% for the nonbreeding season, compared to geolocator estimates alone. Ovenbirds exhibited strong migratory connectivity between breeding and nonbreeding season, which has important implications for various aspects of the ecology, evolution, and conservation. PMID- 26263659 TI - Context-dependent effects of large-wildlife declines on small-mammal communities in central Kenya. AB - Many species of large wildlife have declined drastically worldwide. These reductions often lead to profound shifts in the ecology of entire communities and ecosystems. However, the effects of these large-wildlife declines on other taxa likely hinge upon both underlying abiotic properties of these systems and on the types of secondary anthropogenic changes associated with wildlife loss, making impacts difficult to predict. To better understand how these important contextual factors determine the consequences of large-wildlife declines on other animals in a community, we examined the effects of three common forms of large-wildlife loss (removal without replacement [using fences], removal followed by replacement with domestic stock, and removal accompanied by crop agricultural use) on small-mammal abundance, diversity, and community composition, in landscapes that varied in several abiotic attributes (rainfall, soil fertility, land-use intensity) in central Kenya. We found that small-mammal communities were indeed heavily impacted by all forms of large-wildlife decline, showing, on average: (1) higher densities, (2) lower species richness per site, and (3) different species assemblages in sites from which large wildlife were removed. However, the nature and magnitude of these effects were strongly context dependent. Rainfall, type of land-use change, and the interaction of these two factors were key predictors of both the magnitude and type of responses of small mammals. The strongest effects, particularly abundance responses, tended to be observed in low-rainfall areas. Whereas isolated wildlife removal primarily led to increased small-mammal abundance, wildlife removal associated with secondary uses (agriculture, domestic stock) had much more variable effects on abundance and stronger impacts on diversity and composition. Collectively, these results (1) highlight the importance of context in determining the impacts of large-wildlife decline on small-mammal communities, (2) emphasize the challenges in extrapolating results from controlled experimental studies to predict the effects of wildlife declines that are accompanied by secondary land-uses, and (3) suggest that, because of the context-dependent nature of the responses to large-wildlife decline, large wildlife status alone cannot be reliably used to predict small-mammal community changes. PMID- 26263660 TI - Making biodiversity-friendly cocoa pay: combining yield, certification, and REDD for shade management. AB - The twin United Nations' Millennium Development Goals of biodiversity preservation and poverty reduction both strongly depend on actions in the tropics. In particular, traditional agroforestry could be critical to both biological conservation and human livelihoods in human-altered rainforest areas. However, traditional agroforestry is rapidly disappearing, because the system itself is economically precarious, and because the forest trees that shade traditional crops are now perceived to be overly detrimental to agricultural yield. Here, we show a case where the commonly used agroforestry shade metric, canopy cover, would indeed suggest complete removal of shade trees to maximize yield, with strongly negative biodiversity and climate implications. However, a yield over 50% higher was achievable if approximately 100 shade trees per hectare were planted in a spatially organized fashion, a win-win for biodiversity and the smallholder. The higher yield option was detected by optimizing simultaneously for canopy cover, and a second shade metric, neighboring tree density, which was designed to better capture the yield value of ecological services flowing from forest trees. Nevertheless, even a 50% yield increase may prove insufficient to stop farmers converting away from traditional agroforestry. To further increase agroforestry rents, we apply our results to the design of a sustainable certification (eco-labelling) scheme for cocoa-based products in a biodiversity hotspot, and consider their implications for the use of the United Nations REDD (reducing emissions from deforestation and forest degradation) program in agroforestry systems. Combining yield boost, certification, and REDD has the potential to incentivize eco-friendly agroforestry and lift smallholders out of poverty, simultaneously. PMID- 26263661 TI - Consumption by marine mammals on the Northeast U.S. continental shelf. AB - The economic and ecological impacts of fish consumption by marine mammals, the associated interactions with commercial fish stocks, and the forage demands of these marine mammal populations are largely unknown. Consumption estimates are often either data deficient or not fully evaluated in a rigorous, quantitative manner. Although consumption estimates exist for the Northeast United States (NEUS) Large Marine Ecosystem, there is considerable uncertainty in those estimates. We examined consumption estimates for 12 marine mammal species inhabiting the regional ecosystem. We used sensitivity analyses to examine metabolically driven daily individual consumption rates, resulting in a suite of feasible parameter-pair ranges for each of three taxonomic groups: mysticetes, odontocetes, and pinnipeds. We expanded daily individual consumption to annual consumption based on abundance estimates of marine mammals found on the NEUS continental shelf coupled with estimates of annual residence time for each species. To examine consumptive removals for specific prey, diet compositions were summarized into major prey categories, and predatory removals by marine mammal species as well as for total marine mammal consumption were estimated for each prey taxa. Bounds on consumption estimates for each marine mammal species were determined using Monte Carlo resampling simulations. Our results suggest that consumption for these 12 marine mammal species combined may be similar in magnitude to commercial fishery landings for small pelagic and groundfish prey groups. Consumption by marine mammals warrants consideration both as a source of mortality in assessments of prey-stocks, and to determine marine mammal forage demands in ecosystem assessment models. The approach that we present represents a rigorous, quantitative method to scope the bounds of the biomass that marine mammals are expected to consume, and is appropriate for use in other ecosystems where the interaction between marine mammals and commercial fisheries is thought to be prominent. PMID- 26263662 TI - A comparison of traffic estimates of nocturnal flying animals using radar, thermal imaging, and acoustic recording. AB - There are several remote-sensing tools readily available for the study of nocturnally flying animals (e.g., migrating birds), each possessing unique measurement biases. We used three tools (weather surveillance radar, thermal infrared camera, and acoustic recorder) to measure temporal and spatial patterns of nocturnal traffic estimates of flying animals during the spring and fall of 2011 and 2012 in Lewes, Delaware, USA. Our objective was to compare measures among different technologies to better understand their animal detection biases. For radar and thermal imaging, the greatest observed traffic rate tended to occur at, or shortly after, evening twilight, whereas for the acoustic recorder, peak bird flight-calling activity was observed just prior to morning twilight. Comparing traffic rates during the night for all seasons, we found that mean nightly correlations between acoustics and the other two tools were weakly correlated (thermal infrared camera and acoustics, r = 0.004 +/- 0.04 SE, n = 100 nights; radar and acoustics, r = 0.14 +/- 0.04 SE, n = 101 nights), but highly variable on an individual nightly basis (range = -0.84 to 0.92, range = -0.73 to 0.94). The mean nightly correlations between traffic rates estimated by radar and by thermal infrared camera during the night were more strongly positively correlated (r = 0.39 +/- 0.04 SE, n = 125 nights), but also were highly variable for individual nights (range = -0.76 to 0.98). Through comparison with radar data among numerous height intervals, we determined that flying animal height above the ground influenced thermal imaging positively and flight call detections negatively. Moreover, thermal imaging detections decreased with the presence of cloud cover and increased with mean ground flight speed of animals, whereas acoustic detections showed no relationship with cloud cover presence but did decrease with increased flight speed. We found sampling methods to be positively correlated when comparing mean nightly traffic rates across nights. The strength of these correlations generally increased throughout the night, peaking 2-3 hours before morning twilight. Given the convergence of measures by different tools at this time, we suggest that researchers consider sampling flight activity in the hours before morning twilight when differences due to detection biases among sampling tools appear to be minimized. PMID- 26263663 TI - Modeling elephant-mediated cascading effects of water point closure. AB - Wildlife management to reduce the impact of wildlife on their habitat can be done in several ways, among which removing animals (by either culling or translocation) is most often used. There are, however, alternative ways to control wildlife densities, such as opening or closing water points. The effects of these alternatives are poorly studied. In this paper, we focus on manipulating large herbivores through the closure of water points (WPs). Removal of artificial WPs has been suggested in order to change the distribution of African elephants, which occur in high densities in national parks in Southern Africa and are thought to have a destructive effect on the vegetation. Here, we modeled the long term effects of different scenarios of WP closure on the spatial distribution of elephants, and consequential effects on the vegetation and other herbivores in Kruger National Park, South Africa. Using a dynamic ecosystem model, SAVANNA, scenarios were evaluated that varied in availability of artificial WPs; levels of natural water; and elephant densities. Our modeling results showed that elephants can indirectly negatively affect the distributions of meso-mixed feeders, meso browsers, and some meso-grazers under wet conditions. The closure of artificial WPs hardly had any effect during these natural wet conditions. Under dry conditions, the spatial distribution of both elephant bulls and cows changed when the availability of artificial water was severely reduced in the model. These changes in spatial distribution triggered changes in the spatial availability of woody biomass over the simulation period of 80 years, and this led to changes in the rest of the herbivore community, resulting in increased densities of all herbivores, except for giraffe and steenbok, in areas close to rivers. The spatial distributions of elephant bulls and cows showed to be less affected by the closure of WPs than most of the other herbivore species. Our study contributes to ecologically informed decisions in wildlife management. The results from this modeling exercise imply that long-term effects of this intervention strategy should always be investigated at an ecosystem scale. PMID- 26263664 TI - Bayesian inference and assessment for rare-event bycatch in marine fisheries: a drift gillnet fishery case study. AB - Fisheries bycatch is a global threat to marine megafauna. Environmental laws require bycatch assessment for protected species, but this is difficult when bycatch is rare. Low bycatch rates, combined with low observer coverage, may lead to biased, imprecise estimates when using standard ratio estimators. Bayesian model-based approaches incorporate uncertainty, produce less volatile estimates, and enable probabilistic evaluation of estimates relative to management thresholds. Here, we demonstrate a pragmatic decision-making process that uses Bayesian model-based inferences to estimate the probability of exceeding management thresholds for bycatch in fisheries with < 100% observer coverage. Using the California drift gillnet fishery as a case study, we (1) model rates of rare-event bycatch and mortality using Bayesian Markov chain Monte Carlo estimation methods and 20 years of observer data; (2) predict unobserved counts of bycatch and mortality; (3) infer expected annual mortality; (4) determine probabilities of mortality exceeding regulatory thresholds; and (5) classify the fishery as having low, medium, or high bycatch impact using those probabilities. We focused on leatherback sea turtles (Dermochelys coriacea) and humpback whales (Megaptera novaeangliae). Candidate models included Poisson or zero-inflated Poisson likelihood, fishing effort, and a bycatch rate that varied with area, time, or regulatory regime. Regulatory regime had the strongest effect on leatherback bycatch, with the highest levels occurring prior to a regulatory change. Area had the strongest effect on humpback bycatch. Cumulative bycatch estimates for the 20-year period were 104-242 leatherbacks (52-153 deaths) and 6 50 humpbacks (0-21 deaths). The probability of exceeding a regulatory threshold under the U.S. Marine Mammal Protection Act (Potential Biological Removal, PBR) of 0.113 humpback deaths was 0.58, warranting a "medium bycatch impact" classification of the fishery. No PBR thresholds exist for leatherbacks, but the probability of exceeding an anticipated level of two deaths per year, stated as part of a U.S. Endangered Species Act assessment process, was 0.0007. The approach demonstrated here would allow managers to objectively and probabilistically classify fisheries with respect to bycatch impacts on species that have population-relevant mortality reference points, and declare with a stipulated level of certainty that bycatch did or did not exceed estimated upper bounds. PMID- 26263665 TI - Predicting the spread of aquatic invaders: insight from 200 years of invasion by zebra mussels. AB - Understanding factors controlling the introduction and spread of species is crucial to improving the management of both natural populations and introduced species. The zebra mussel, Dreissena polymorpha, is considered the most aggressive freshwater invader in the Northern Hemisphere, and is a convenient model system for invasion biology, offering one of the best aquatic examples for examining the invasion process. We used data on 553 of the 1040 glacial lakes in the Republic of Belarus that were examined for the presence of zebra mussels. We used these data to build, test, and construct modified models to predict the spread of this invader, including selection of important parameters that could limit the spread of this invader. In spite of 200 years of continuous invasion, by 1996, zebra mussels were found in only 16.8% of all lakes studied. Of those lakes without zebra mussels in 1996, 66% were predicted to be susceptible to invasion by zebra mussels in the future, and 33% were predicted to be immune to successful invasion due to their water chemistry. Eighty lakes free of zebra mussels in 1996 were reexamined from 1997 to 2008. Of these, zebra mussels successfully invaded an additional 31 lakes, all of which were classified initially as suitable for zebra mussels; none of the lakes previously classified as unsuitable were invaded. We used the Random Forests classification algorithm with 16 environmental variables to determine the most important factors that differed between invaded lakes and those lakes suitable for invasion that have not yet been invaded. Distance to the nearest infested lakes was found to be the most important variable, followed by the lake area, color, average depth, and concentration of chloride, magnesium, and bicarbonate. This study provides a useful approach for predicting the spread of an invader across a landscape with variable habitat suitability that can be applied to a variety of species and systems. PMID- 26263666 TI - Evidence-based tool surpasses expert opinion in predicting probability of eradication of aquatic nonindigenous species. AB - The main objective of evidence-based management is to promote use of scientific data in the decision-making process of managers, with data either complementing or replacing expert knowledge. It is expected that this will increase the efficiency of environmental interventions. However, the relative accuracy and precision of evidence-based tools and expert knowledge has seldom been evaluated. It is therefore essential to verify whether such tools provide better decision support before advocating their use. We conducted an elicitation survey in which experts were asked to (1) evaluate the influence of various factors on the success of eradication programs for aquatic nonindigenous species and (2) provide probabilities of success for real case studies for which we knew the outcome. The responses of experts were compared with the results and predictions of a newly developed evidence-based tool: a statistical model calibrated with a meta analysis of case studies designed to evaluate probability of eradication. Experts and the model generally identified the same factors as influencing the probability of success. However, the model provided much more accurate estimates for the probability of eradication than expert opinion, strongly suggesting that an evidence-based approach is superior to expert knowledge in this case. Uncertainty surrounding the predictions of the evidence-based tool was similar to among-expert variability. Finally, a model based on >30 case studies returned more accurate predictions than expert opinion. We conclude that decision-making processes based on expert judgment would greatly benefit from incorporating evidence-based tools. PMID- 26263667 TI - Signatures of human impact: size distributions and spatial organization of wetlands in the Prairie Pothole landscape. AB - More than 50% of global wetland area has been lost over the last 200 years, resulting in losses of habitat and species diversity as well as decreased hydrologic and biogeochemical functionality. Recognition of the magnitude of wetland loss as well as the wide variety of ecosystem services provided by wetlands has in recent decades led to an increased focus on wetland restoration. Restoration activities, however, often proceed in an ad hoc manner, with a focus on maximizing the total restored area rather than on other spatial attributes of the wetland network, which are less well understood. In this study, we have addressed the question of how human activities have altered the size distribution and spatial organization of wetlands over the Prairie Pothole Region of the Des Moines Lobe using high- resolution LIDAR data. Our results show that as well as the generally accepted 90% loss of depressional wetland area, there has been a preferential loss of smaller wetlands, with a marked alteration of the historical power-law relationship observed between wetland size and frequency and a resulting homogenization of the wetland size distribution. In addition, our results show significant decreases in perimeter-to-area ratios, increased mean distances between wetlands, particularly between smaller wetlands, and a reduced likelihood that current wetlands will, be located in upland areas. Such patterns of loss can lead to disproportionate losses of ecosystem services, as smaller wetlands with larger perimeter-to- area ratios have been found to provide higher rates of biogeochemical processing and groundwater recharge, while increased mean distances between wetlands hinder species migration and thus negatively impact biodiversity. These results suggest the need to gear restoration efforts toward understanding and recreating the size distribution and spatial organization of historical wetlands, rather than focusing primarily on an increase in overall area. PMID- 26263668 TI - Biotic resistance, disturbance, and mode of colonization impact the invasion of a widespread, introduced wetland grass. AB - Disturbance and biotic resistance are important factors driving plant invasions, but how these factors interact for plants with different modes of colonization (i.e., sexual and asexual) is unclear. We evaluated factors influencing the invasion of nonnative Phragmites australis, which has been rapidly expanding in brackish tidal wetlands in Chesapeake Bay. We conducted a survey of naturally occurring small-scale disturbances (removal of vegetation and/or sediment deposition) across four plant communities; determined the effects of small-scale disturbance and biotic resistance on P. australis seedling and rhizome emergence; and tested the effects of size and frequency of small-scale disturbances on seedling emergence and survival of transplanted seedlings. The results of our study demonstrate that the invasion window for seeds is in disturbed areas in high-marsh plant communities that flood less frequently; seedling emergence in undisturbed areas was negligible. Establishment of shoots from rhizome segments was low in all plant communities. Disturbance size and frequency had no significant impact on seed germination and seedling survival. Our findings provide evidence that small-scale within-wetland disturbances are important for the invasion of the nonnative lineage of P. australis by seeds in brackish tidal wetlands in Chesapeake Bay. Efforts to reduce disturbances, large and small, in wetlands can be used to limit P. australis invasion by seed, but invasion by rhizome is still likely to occur across many plant communities irrespective of the presence of disturbance. PMID- 26263669 TI - Group-based modeling of ecological trajectories in restored wetlands. AB - Repeated measures taken at the same restoration sites over time are used to describe restoration trajectories and identify sites that are trending toward unexpected outcomes. Analogously, social scientists use repeated measures of individuals to describe developmental trajectories of behaviors or other outcomes. Group-based trajectory modeling (GBTM) is one statistical method used in behavioral and health sciences for this purpose. I introduce the use of GBTM to identify clusters of similar restoration trajectories within a sample of sites. Data collected at 54 restored wetlands in Illinois for up to 15 years post restoration were used to describe trajectories of six indicators: plant species richness, number of Carex (sedge) species, mean coefficient of conservatism (mean C), native plant cover, perennial plant cover, and planted species cover. For each indicator, I used GBTM to classify wetlands into three to four groups with distinct trajectories. In general, cover by native and planted species declined, while species richness and mean C increased over time or peaked then declined. Site context and management may explain trajectory group membership. Specifically, wetlands restored more recently and those restored within forested contexts were more likely to follow increasing trajectories. I show GBTM to be useful for identifying typical restoration trajectory patterns, developing hypotheses regarding factors driving those patterns and pinpointing critical times for intervention. Furthermore, GBTM might be applied more broadly in ecological research to identify common patterns of community assembly in large numbers of plots or sites. PMID- 26263670 TI - Assessing biophysical controls on Gulf of Mexico hypoxia through probabilistic modeling. AB - A mechanistic model was developed to predict midsummer bottom-water dissolved oxygen (BWDO) concentration and hypoxic area on the Louisiana shelf of the northern Gulf of Mexico, USA (1985-2011). Because of its parsimonious formulation, the model possesses many of the benefits of simpler, more empirical models, in that it is computationally efficient and can rigorously account for uncertainty through Bayesian inference. At the same time, the model incorporates important biophysical processes such that its parameterization can be informed by field-measured biological and physical rates. The model is used to explore how freshwater flow, nutrient load, benthic oxygen demand, and wind velocity affect hypoxia on the western and eastern sections of the shelf, delineated by the Atchafalaya River outfall. The model explains over 70% of the variability in BWDO on both shelf sections, and outperforms linear regression models developed from the same input variables. Model results suggest that physical factors (i.e., wind and flow) control a larger portion of the year-to-year variability in hypoxia than previously thought, especially on the western shelf, though seasonal nutrient loads remain an important driver of hypoxia, as well. Unlike several previous Gulf hypoxia modeling studies, results do not indicate a temporal shift in the system's propensity for hypoxia formation (i.e., no regime change). Results do indicate that benthic oxygen demand is a substantial BWDO sink, and a better understanding of the long-term dynamics of this sink is required to better predict how the size of the hypoxic zone will respond to proposed reductions in nutrient loading. PMID- 26263671 TI - Demographic drivers of tree biomass change during secondary succession in northeastern Costa Rica. AB - Second-growth tropical forests are an important global carbon sink. As current knowledge on biomass accumulation during secondary succession is heavily based on chronosequence studies, direct estimates of annual rates of biomass accumulation in monitored stands are largely unavailable. We evaluated the contributions of tree diameter increment, recruitment, and mortality to annual tree biomass change during succession for three groups of tree species: second-growth (SG) specialists, generalists, and old-growth (OG) specialists. We monitored six second-growth tropical forests that varied in stand age and two old-growth forests in northeastern Costa Rica. We monitored these over a period of 8 to 16 years. To assess rates of biomass change during secondary succession, we compared standing biomass and biomass dynamics between second-growth forest stages and old growth forest, and evaluated the effect of stand age on standing biomass and biomass dynamics in second-growth forests. Standing tree biomass increased with stand age during succession, whereas the rate of biomass change decreased. Biomass change was largely driven by tree diameter increment and mortality, with a minor contribution from recruitment. The relative importance of these demographic drivers shifted over succession. Biomass gain due to tree diameter increment decreased with stand age, whereas biomass loss due to mortality increased. In the age range of our second-growth forests, 10-41 years, SG specialists dominated tree biomass in second-growth forests. SG specialists, and to a lesser extent generalists, also dominated stand-level biomass increase due to tree diameter increment, whereas SG specialists largely accounted for decreases in biomass due to mortality. Our results indicate that tree growth is largely driving biomass dynamics early in succession, whereas both growth and mortality are important later in succession. Biomass dynamics are largely accounted for by a few SG specialists and one generalist species, Pentaclethra macroloba. To assess the generality of our results, similar long-term studies should be compared across tropical forest landscapes. PMID- 26263672 TI - Nontarget herbivory by a weed biocontrol insect is limited to spillover, reducing the chance of population-level impacts. AB - Insects approved for classical biocontrol of weeds are often capable of using close relatives of their target weed for feeding, oviposition, or larval development, with reduced preference and performance. When nontarget herbivory occurs and is suspected to reduce survival, growth, or fecundity of individual plants, and insects are capable of reproducing on their nontarget host, characterization of spatial and temporal patterns of the occurrence and intensity of herbivory is valuable for predicting potential population-level effects. Here, we perform a novel post-release manipulative field experiment with a root-feeding biocontrol weevil, Mogulones crucifer, released in Canada to control the rangeland weed Cynoglossum officinale, to test for its ability to establish on the nontarget plant Hackelia micrantha. After Cynoglossum, M. crucifer exhibits its highest preference for and performance on Hackelia spp. We released M. crucifer on Canadian rangeland sites with naturally occurring populations of H. micrantha growing interspersed with the target weed or in the near absence of the target weed. Adult weevil feeding on surrounding plants was monitored for three summers after release (years 0, 1, and 2), and, subsequently, subsets of plants were destructively sampled to determine M. crucifer oviposition levels. Additional oviposition and larval development data were obtained from seven non experimental sites where weevils were released zero, three, or four years earlier. M. crucifer was not detected on experimental sites without C. officinale after two years, and nontarget herbivory was restricted to rare, low-level spillover. Visible evidence of adult herbivory (i.e., scars on shoots) was associated with oviposition in 90% of targets but only 30% of nontarget plants. We infer, through ecological refuge theory, that nontarget population-level impacts from M. crucifer spillover are unlikely because of temporal, spatial, and probabilistic refuges from herbivory, and make recommendations for monitoring and management of biocontrol systems with similar attributes, such as removing target plants around nontarget populations of interest. Because M. crucifer is among the least host-specific of the modern weed biocontrol agents, and H. micrantha is likely one of its most highly preferred nontargets, these conclusions are, arguably, generally applicable to other nontarget plants and biocontrol systems. PMID- 26263673 TI - Long-term climate change mitigation potential with organic matter management on grasslands. AB - Compost amendments to grasslands have been proposed as a strategy to mitigate climate change through carbon (C) sequestration, yet little research exists exploring the net mitigation potential or the long-term impacts of this strategy. We used field data and the DAYCENT biogeochemical model to investigate the climate change mitigation potential of compost amendments to grasslands in California, USA. The model was used to test ecosystem C and greenhouse gas responses to a range of compost qualities (carbon to nitrogen [C:N] ratios of 11.1, 20, or 30) and application rates (single addition of 14 Mg C/ha or 10 annual additions of 1.4 Mg C . ha(-1) . yr(-1)). The model was parameterized using site-specific weather, vegetation, and edaphic characteristics and was validated by comparing simulated soil C, nitrous oxide (N2O), methane (CH4), and carbon dioxide (CO2) fluxes, and net primary production (NPP) with three years of field data. All compost amendment scenarios led to net greenhouse gas sinks that persisted for several decades. Rates of climate change mitigation potential ranged from 130 +/- 3 g to 158 +/- 8 g CO2-eq . m(-2) .yr(-1) (where "eq" stands for "equivalents") when assessed over a 10-year time period and 63 +/- 2 g to 84 +/- 10 g CO2- eq . m(-2) . yr(-1) over a 30-year time period. Both C storage and greenhouse gas emissions increased rapidly following amendments. Compost amendments with lower C:N led to higher C sequestration rates over time. However, these soils also experienced greater N20 fluxes. Multiple smaller compost additions resulted in similar cumulative C sequestration rates, albeit with a time lag, and lower cumulative N2O emissions. These results identify a trade-off between maximizing C sequestration and minimizing N2O emissions following amendments, and suggest that compost additions to grassland soils can have a long term impact on C and greenhouse gas dynamics that contributes to climate change mitigation. PMID- 26263674 TI - Model-data assimilation of multiple phenological observations to constrain and predict leaf area index. AB - Our limited ability to accurately simulate leaf phenology is a leading source of uncertainty in models of ecosystem carbon cycling. We evaluate if continuously updating canopy state variables with observations is beneficial for predicting phenological events. We employed ensemble adjustment Kalman filter (EAKF) to update predictions of leaf area index (LAI) and leaf extension using tower-based photosynthetically active radiation (PAR) and moderate resolution imaging spectrometer (MODIS) data for 2002-2005 at Willow Creek, Wisconsin, USA, a mature, even-aged, northern hardwood, deciduous forest. The ecosystem demography model version 2 (ED2) was used as the prediction model, forced by offline climate data. EAKF successfully incorporated information from both the observations and model predictions weighted by their respective uncertainties. The resulting. estimate reproduced the observed leaf phenological cycle in the spring and the fall better than a parametric model prediction. These results indicate that during spring the observations contribute most in determining the correct bud burst date, after which the model performs well, but accurately modeling fall leaf senesce requires continuous model updating from observations. While the predicted net ecosystem exchange (NEE) of CO2 precedes tower observations and unassimilated model predictions in the spring, overall the prediction follows observed NEE better than the model alone. Our results show state data assimilation successfully simulates the evolution of plant leaf phenology and improves model predictions of forest NEE. PMID- 26263675 TI - Portfolio conservation of metapopulations under climate change. AB - Climate change is likely to lead to increasing population variability and extinction risk. Theoretically, greater population diversity should buffer against rising climate variability, and this theory is often invoked as a reason for greater conservation. However, this has rarely been quantified. Here we show how a portfolio approach to managing population diversity can inform metapopulation conservation priorities in a changing world. We develop a salmon metapopulation model in which productivity is driven by spatially distributed thermal tolerance and patterns of short- and long-term climate change. We then implement spatial conservation scenarios that control population carrying capacities and evaluate the metapopulation portfolios as a financial manager might: along axes of conservation risk and return. We show that preserving a diversity of thermal tolerances minimizes risk, given environmental stochasticity, and ensures persistence, given long-term environmental change. When the thermal tolerances of populations are unknown, doubling the number of populations conserved may nearly halve expected metapopulation variability. However, this reduction in variability can come at the expense of long-term persistence if climate change increasingly restricts available habitat, forcing ecological managers to balance society's desire for short-term stability and long term viability. Our findings suggest the importance of conserving the processes that promote thermal-tolerance diversity, such as genetic diversity, habitat heterogeneity, and natural disturbance regimes, and demonstrate that diverse natural portfolios may be critical for metapopulation conservation in the face of increasing climate variability and change. PMID- 26263676 TI - Identifying habitats at risk: simple models can reveal complex ecosystem dynamics. AB - The relationship between ecological impact and ecosystem structure is often strongly nonlinear, so that small increases in impact levels can cause a disproportionately large response in ecosystem structure. Nonlinear ecosystem responses can be difficult to predict because locally relevant data sets can be difficult or impossible to obtain. Bayesian networks (BN) are an emerging tool that can help managers to define ecosystem relationships using a range of data types from comprehensive quantitative data sets to expert opinion. We show how a simple BN can reveal nonlinear dynamics in seagrass ecosystems using ecological relationships sourced from the literature. We first developed a conceptual diagram by cataloguing the ecological responses of seagrasses to a range of drivers and impacts. We used the conceptual diagram to develop a BN populated with values sourced from published studies. We then applied the BN to show that the amount of initial seagrass biomass has a mitigating effect on the level of impact a meadow can withstand without loss, and that meadow recovery can often require disproportionately large improvements in impact levels. This mitigating effect resulted in the middle ranges of impact levels having a wide likelihood of seagrass presence, a situation known as bistability. Finally, we applied the model in a case study to identify the risk of loss and the likelihood of recovery for the conservation and management of seagrass meadows in Moreton Bay, Queensland, Australia. We used the model to predict the likelihood of bistability in 23 locations in the Bay. The model predicted bistability in seven locations, most of which have experienced seagrass loss at some stage in the past 25 years providing essential information for potential future restoration efforts. Our results demonstrate the capacity of simple, flexible modeling tools to facilitate collation and synthesis of disparate information. This approach can be adopted in the initial stages of conservation programs as a low-cost and relatively straightforward way to provide preliminary assessments of.nonlinear dynamics in ecosystems. PMID- 26263677 TI - [NEUROENDOCRINE REPRODUCTIVE CENTERS OF CORTICOMEDIAL DIVISION OF THE AMYGDALA]. AB - In this review for the first time systematized available in modern literature data, which characterize the structural and functional organization of the reproductive centers of corticomedial division of the Amygdala. Given information about physiological mechanisms of their involvement in the organization of sexual behavior, regulation of secretion and excretion of gonadotropines, influence on the processes of sexual maturation of organisms. Involvement of Amygdala in functional systems of the brain, which determine reproductive functions, predefined its participation in the processes of sexual differentiation of the brain. Important role in the implementation of reproductive functions plays the olfactory stimuli, which through the Amygdala switches to the centers of the pre optic-hypothalamic region, which controls the secretion of gonadotropins and sexual behavior. PMID- 26263678 TI - [C-TYPE NATRIURETIC PEP- TIDE: WHAT, WHERE AND WHAT FOR IS THIS?]. AB - The up-to-day world-wide data about the structure, distribution, and physiological effects of the most poorly known among the natriuretic peptides- the C-type (CNP)--are summarized in the review. Despite its name, this peptide does not stimulate sodium excretion but shares the prominent vasodilating and antyproliferating effects in different organs and tissues. The special emphasis is attended to CNP functions in central nervous system. The information about the peptide molecular biology, including intracellular processing, blood peptide concentration, specific receptors structure, and signaling pathways in target cells is presented. PMID- 26263679 TI - [IMPACT OF LONG-TERM ADAPTATION TO COLD ON THE STATE OF CARDIOVASCULAR SYSTEM]. AB - The inhabitancy in Far North increases a probability of development of coronary heart disease, acute myocardial infarction and arterial hypertension. Catecholamines and NO deficiency play a substantial role in the development of cold hypertension but are not involved in acclimatization cardiac hypertrophy. Data of in vivo experiments indicate in favor of an involvement of alpha adrenergic receptors (ARs) in the mechanism of an appearance of cold hypertension. Cold acclimatization promotes an elevation of beta3-AR density and decrease in beta1-AR and beta2-AR quantity on sarcolemma of cardiomyocytes. Experimental data indicate about the important role of aldosterone and angiotensin-II in the development of acclimatization hypertension. Catecholamines, aldosterone and angiotensin-II are not involved in cold hypertrophy of heart. Experimental data say on the important role of endothelin ETA-receptor in the formation of cold hypertrophy of heart and cardiofibrosis. Thyroid hormones play substantial role in the development of cold hypertension and cardiac hypertrophy. PMID- 26263680 TI - [THE EFFECTS OF THE STIMULATION OF HYPOTHALAMIC NUCLEI ON THE INFERIOR VESTIBULAR NUCLEUS AFTER LONG-TERM VIBRATION ACTION AND ADMINISTRATION OF PROLINE RICH PEPTIDE-1]. AB - Vestibular dysfunctions after vibration action in a considerable degree by adaptive-adjustment changes of neurotransmitter processes are determined and regulation of which is possible by endogenous factors, particularly hypothalamic proline rich peptide-1. On Albino rats synaptic changes in single neurons of the inferior vestibular nucleus during high-frequency stimulation of hypothalamic supraoptic and paraventricular nuclei in condition of vibration action and systemic use of proline rich peptide-1 were studied. The poststimulus spike activity of inferior vestibular nucleus neurons in norm was manifested mainly in the form of tetanic potentiation and posttetanic potentation after vibration action. The combination of vibration action and proline rich peptide-1 restores the true balance of excitatory and inhibitory poststimulus reactions and increased level of survival the inferior vestibular nucleus neurons. PMID- 26263681 TI - [THE EFFECTS OF CHRO- NIC ADMINISTRATION OF MODERATE DOSE OF PROINFLAMMATORY CYTOKINE INTERLEUKIN-1beta ON RAT INVESTIGATIVE BEHAVIOR AND SPATIAL MEMORY]. AB - The aim of this study was to discover the effects of chronic intraperitoneal administration of proinflammatory cytokine interleukin-1beta (IL-1beta) on rat investigative behavior and spatial memory. Rats were injected with a moderate pyrogenic dose of IL-1beta (0.5 mkg/kg) daily during 14 days (7 days before tests and 7 testing days). The behavior was examined in 23.5 hours after the previous injection of cytokine. The test battery included: "The open field" (within 3 consecutive days), "The exploration of novel objects", and "The Morris water maze". The animals treated with IL-1beta differed from the control animals in an essential decrease of locomotor activity, slight increase of anxiety and suppression of exploratory behavior. The impairment of spatial memory was not revealed. PMID- 26263682 TI - [MORPHOLOGICAL AND VISCOELASTIC PROPERTIES OF ISIAH RATS MYOCARDIUM DURING THE DEVELOPMENT OF ARTERIAL HYPERTENSION]. AB - The comprehensive study of morphometrical parameters and viscoelastic properties of right ventricle and left ventricle papillary muscles of ISIAH rats during the development of arterial hypertension has been carried out. It is established the significant increase of the index of heart mass to body mass and to tibia length of ISIAH rats in comparison with WAG rats of the same age. There are no any significant differences of "stress-strain" dependences of all experimental groups. PMID- 26263683 TI - [THE CHARACTERISTICS OF RETINA AT THE DEVELOPMENT OF PROLIFERATIVE VITREORETINOPATHY IN RATS AFTER INTRAOCULAR INJECTION OF CONCANAVALIN A AND DISPASE]. AB - In this article we review and discuss the advantages of two proliferative vitreoretinopathy models in rats: intravitreal injection of proteolytic enzyme dispase and proinflammatory lectin concanavalin A. For the first time we selected clear morphological criteria for the retina evaluation during the inflammatory response. We also compared the effects of the injection of dispase and concanavalin on the 7th day after the drugs administration. We conclude that different doses of dispase can be used to get a stable model of PVR on different periods after the injection procedure. PMID- 26263684 TI - [BEHAVIOR, MEMORY AND IMMUNOLOGICAL STATUS IN MICE MODEL OF DESYNCHRONOSIS]. AB - Interstrain differences in behavior and parameters of the immune system of CBA and C57BL/6 mice with round the clock coverage (KO) were investigated. Open field, light/dark, acoustic startle response, forced swimming, elevated plus maze, passive avoidance were used for measuring emotional behavior and memory. The number of lymphocyte subpopulations CD3+, CD4+8-, CD4-8+, CD4+8+, CD19+, CD3+hi spleen and thymus, the ratio of cells in different phases of the cell cycle was determined by flow cytometry. C57BL/6J mice strictly increased anxiety in response to the KO compared to CBA mice. Moreover, KO-treated C57BL/6J mice impaired the passive avoidance learning. We found that KO evoked significant changes in the cellular composition of the thymus and decrease of thymocytes proliferation in C57BL/6J mice. In opposite KO-treated CBA mice showed change of splenic cellular structure with increased % CD19+ cells and the proliferation of splenocytes. Our study demonstrated genotype-dependent reactions of the nervous and immune systems in response chronic constant light. PMID- 26263685 TI - [IMPACT OF INDIVIDUAL PERSONALITY FEATURES ON ABILITY TO VOLUNTARY REGULATION OF EXPRESSION EEG ALPHA AND BETA FREQUENCIES]. AB - The ability to voluntary control severity of alpha- and beta-2 frequency bands in the parietal and frontal cortical areas was investigated at 17 volunteers using biofeedback. The impact of different personality traits on the effectiveness of control was evaluated. According to the data, it was easier task to decrease expression beta-2 frequency in the frontal cortex than to decline the power of alpha frequency in the parietal cortex. The effectiveness of voluntary control of brain activity is influenced by personality features as extraversion, psychoticism, neuroticism, mobility and steadiness of nerve processes, level of person anxiety. PMID- 26263686 TI - [DETAILED RESEARCH OF THE ONTOGENETIC CHANGES IN EEG PARAMETERS MEN AND WOMEN DURING THE REPRODUCTIVE PERIOD]. AB - The changes of 272 EEG parameters in 252 women and 97 men during the period of life of 16 to 45 years in increments of one month were investigated. Correlation analysis and approximations were used. Ontogenetic regression of amplitude and power amplitude and power of alpha, theta, delta, but not beta rhythms predominantly in the right posterior cortex leads in women was more regressive than in men was shown. Overall ontogenetic tendency to fall to the nonlinear amplitude and power of EEG rhythms with age is reproduced in both sexes. Frequency of rhythms in the course of ontogeny, as a rule, was the compensatory increase. So, in neurologically healthy men and women differently achieved the same goal--adaptive response of the brain to age conversion. PMID- 26263687 TI - [Root Nodule Bacteria Sinorhizobium meliloti: Tolerance to Salinity and Bacterial Genetic Determinants]. AB - The theoretical and experimental data on salt tolerance of root nodule bacteria Sinorhizobium meliloti (Ensifer meliloti), an alfalfa symbiont, and on genetic determination of this feature are reviewed. Extensive data on the genes affecting adaptation of proteobacteria are provided, as well as on the groups of genes with activity depending on the osmolarity of the medium. Structural and functional polymorphism of the bet genes involved in betaine synthesis and transport in S. meliloti is discussed. The phenotypic and. genotypic polymorphism in 282 environmental rhizobial strains isolated from the centers of alfalfa diversity affected by aridity and salinity is discussed. The isolates from the Aral Sea area and northern Caucasus were shown to possess the betC gene represented by two types of alleles: the dominant A-type allele found in Rm 1021 and the less common divergent E-type allele, which was revealed in regions at the frequencies at the frequencies of 0.35 and 0.48, respectively. In the isolates with the salt tolerant phenotype, which were isolated from root nodules and subsequently formed less effective symbioses with alfalfa, the frequency of E-type alleles was 2.5 times higher. Analysis of the nucleotide and amino acid sequences of the E-type allele of the betC gene revealed that establishment of this allele in the population was a result of positive selection. It is concluded that diversification of the functionally diverse bet genes occurring in S. meliloti affects the salt tolerance and symbiotic effectivity of rhizobia. PMID- 26263688 TI - [Regulation of Biofilm Formation by Pseudomonas chlororaphis in an vitro System]. AB - The mutants of Pseudomonas chlororaphis 449 with completely or partially suppressed accumulation of N-acyl homoserine lactones exhibited the absence or a pronounced decrease of their capacity for stimulation of biofilm growth in the presence of azithromycin. Biofilms of the wild type strain preformed in the presence of the stimulatory azithromycin concentrations exhibited more intense staining with a polysaccharide-specific dye 1,9-dimethyl methylene blue (DMMB) and were more resistant to heat shock. These findings indicate accumulation of the structural matrix polysaccharides, which play a protective role under the conditions of thermal shock. Extremely low azithromycin concentrations (0.001 0.01 MUg/mL) inhibit biofilm formation by P. chlororaphis 449 and P. chlororaphis 66 with suppression of the synthesis of DMMB-staining polysaccharides. PMID- 26263689 TI - [Applicability of MALDI Mass Spectrometry for Diagnostics of Phase Variants in Bacterial Populations]. AB - Efficiency of MALDI mass spectrometry for differentiation between phenotypic phase variants (in colony morphology and virulence/avirulence) was investigated.for saprotrophic and opportunistically pathogenic bacteria of five genera (Acinetobacter, Arthrobacter, Rhodococcus, Corynebacterium, and Escherichia). Analysis of MALDI spectra (on the SA and HCCA matrices) included: (1) determination of similarity of the protein spectra as a percentage of the common protein peaks to the total amount of proteins, which reflects the phylogenetic relationships of the objects and has been recommended for identification of closely related species; (2) comparison of intensities of the common peaks; and (3) the presence of specific peaks as determinative characteristics of the variants. Under the standard analytical conditions the similarity between the MALDI profiles was shown to increase in the row: genus species-strain-variant. Assessment of intensities of the common peaks was most applicable for differentiation between phase variants, especially in the case of high similarity of their profiles. Phase variants (A. oxydans strain K14) with similar colony morphotypes (S, R, M, and S(m)) grown on different media (LB agar, TSA, and TGYg) exhibited differences in their protein profiles reflecting the differences in their physiological characteristics. This finding is in agreement with our previous results on screening of the R. opacus with similar colony morphology and different substrate specificity in decomposition of chlorinated phenols. Analysis of MALDI spectra is probably the only efficient method for detection of such variants. PMID- 26263690 TI - [Poly- beta -Hydroxybutyrate Accumulation by Rhodobacter sphaeroides Phase Variants]. AB - The Rand M variants of a purple photosynthetic bacterium Rhodobacter sphaeroides 2R grown on a medium with acetate accumulate poly- beta-hydroxybutyrate (PHB). Accumulation of this polymer occurs in the cells grown either anaerobically on the light or aerobically in the dark. On the medium with C/N imbalance (C/N = 4), PHB content during the stationary growth phase under aerobic conditions in the dark was 40 and 70% of the dry biomass of the R and M variant, respectively. The Rba. sphaeroides M variant is therefore a promising culture for large-scale PHB production. Investigation of activity of the TCA cycle enzymes revealed that decreased activity of citrate synthase, the key enzyme for acetate involvement in the reactions of the tricarboxylic acids cycle, was primarily responsible for enhanced PHB synthesis by Rba. sphaeroides. Moreover, the Rba. sphaeroides M variant grown under aerobic conditions in the dark exhibited considerably lower activity of NADH oxidase, which participates in the oxidation of reduced NADH produced in the TCA cycle during acetate oxidation. The combination of these two factors increases the possibilities for acetate assimilation via an alternative mechanism of PHB synthesis. PMID- 26263691 TI - [Screening of Producers of Proteinases with Fibrinolytic and Collagenolytic Activities among Micromycetes]. AB - Screening for producers of proteinases with fibrinolytic (plasmin-like and plasminogen-activating) and collagenolytic activities-was carried out among 83 strains of microscopic fungi belonging to various ecological groups. Entomopathogenic micromycetes secreted proteinases with higher fibrinolytic and collagenolytic activity than saprotrophic, potentially phytopathogenic, and epiphytic strains. Micromycete strains possessing proteolytic enzymes with collagenase activity were revealed, as well as the strains producing proteinases with plasmin-like activity. None of the strains studied secreted proteinases possessing only plasminogen-activating activity. Tolypocladium inflatum k1 was found to be a producer of extracellular proteinases with high plasminogen activating, plasmin-like, and collagenolytic activities. The specific plasminogen activating activity of T. inflatum k1 was shown to be 20% higher than its plasmin like activity. PMID- 26263692 TI - [Physiological Properties of Acidithiobacillus ferrooxidans Strains Isolated from Sulfide Ore Deposits in Kazakhstan]. AB - Acidithiobacillus ferroxidans strains were isolated from acidophilic microbial communities of Kazakhstan sulfide ore deposits. Their biotechnologically important properties (optimal and maximal growth temperatures and resistance to NaCl) were determined. While temperature optima of the strains were the same (30 32 degrees C), temperature ranges were different. Thus, strain TFBK oxidized iron very poorly at 37 degrees C, while for strain TFV, the iron oxidation rate at this temperature was insignificantly lower than at lesser temperatures. NaCl inhibited the oxidative activity of both strains. Iron oxidation by strain TFV was inhibited at 5 g/L NaCl and was suppressed almost completely at 20 g/L. Iron oxidation by strain TFBK was inhibited by NaCl to a lesser degree, so that iron oxidation rate was relatively high at 10 g/L, while at 20 g/L NaCl the process was not suppressed completely, although the oxidation rate was low. Sulfur oxidation by these strains was less affected by NaCl than oxidation of ferrous iron. Sulfur oxidation by strain TFV was considerably inhibited only at 20 g/L NaCl, but was not suppressed completely. Sulfur oxidation by strain TFBK was more affected by NaCl. At 10 g/L NaCl the oxidation rate was much lower than at lower NaCl concentrations (sulfate concentrations after 6 days of oxidation at 5 and 10 g/L NaCl were -130 and -100 mM, respectively). While sulfur oxidation by strain TFBK was considerably inhibited at 10 and 20 g/L NaCl, similar to strain TFV it was not suppressed completely. Our results indicate the adaptation of the species A. ferrooxidans to a broad range of growth conditions. PMID- 26263693 TI - [Identification of Hydrocarbon-Oxidizing Dietzia Bacteria from Petroleum Reservoirs Based on Phenotypic Properties and Analysis of the 16S rRNA and gyrB Genes]. AB - The taxonomic position of hydrocarbon-oxidizing bacterial strains 263 and 32d isolated from formation water of the Daqing petroleum reservoir (PRC) was determined by polyphasic taxonomy techniques, including analysis of the 16S rRNA and the gyrB genes. The major chemotaxonomic characteristics of both strains, including the IV type cell wall, composition of cell wall fatty acids, mycolic acids, and menaquinones, agreed with those typical of Dietzia strains. The DNA G+C content of strains 263 and 32d were 67.8 and 67.6 mol%, respectively. Phylogenetic analysis of the 16S rRNA gene of strain 32d revealed 99.7% similarity to the gene of D. maris, making it possible to identify strain 32d as belonging to this species. The 16S rRNA gene sequence of strain 263 exhibited 99.7 and 99.9% similarity to those of D. natronolimnaea and D. cercidiphylli YIM65002(T), respectively. Analysis of the gyrB genes of the subterranean isolates and of a number of Dietzia type strains confirmed classiffication of strain 32d as a D. maris strain and of strain 263, as a D. natronolimnaea strain. A conclusion was made concerning higher resolving power of phylogenetic analysis of the gyrB gene compared to the 16S rRNA gene analysis in the case of determination of the species position of Dietzia isolates. PMID- 26263694 TI - [Formation of 55-kDa Fragments under Impaired Coordination Bonds and Hydrophobic Interactions in Peripheral Light-Harvesting Complexes Isolated from Photosynthetic Purple Bacteria]. AB - Size exclusion chromatography was used to assess the relative size of intact and diphenylamine-treated (DPA, with suppressed carotenoid synthesis) peripheral light-harvesting complexes (LH2 complexes) of the sulfurbacterium Allochromatium minutissimum. Both LH2 complexes were nonamers and had the same elution volume V(e), coinciding with that for the LH2 complex of Rhodoblastus acidophilus (strain 10050). Their molecular mass was 150 kDa. Bot pheophytinization of bacteriochlorophyll (BChl) at low pH and treatment with the detergent LDAO, affecting the hydrophobic interactions between the neighboring protomers, result in the fragmentation of the ring of the isolated LH2 complexes and formation of 55-kDa fragments with molecular masses corresponding to one-third of the initial value. Fragmentation caused by both pheophytinization and detergent treatment was much more rapid in DPA-treated LH2 complexes than in the intact ones. The 55-kDa fragments formed at low pH values contained monomeric bacteriopheophytin, while the fragments of a similar molecular mass formed at pH 8.0 in the presence of the detergent contained monomeric BChl. The observed fragmentation was hypothesized to reflect the inherent C3 symmetry of the LH2 complexes, with the preliminarily assembled trimers used as building blocks. PMID- 26263695 TI - [New Approaches for the Isolation of Bifidobacterial Strains, Their Molecular Characterization, and Assessment of Their Probiotic Potential]. AB - Six stably growing strains of bifidobacteria possessing probiotic properties were isolated from the feces of newborn children and animals. According to the results of molecular analysis, one strain was classified as Bifidobacterium bifidum, while five belonged to Bifidobacterium animalis. Initial identification of the strains was carried out using the primer pairs for the 16S rRNA gene (g-Bifid F/R, Bif164/662) and for the xfp gene specific for bifidobacteria. Subsequent sequencing of complete genes encoding 16S rRNA synthesis in the isolates confirmed their species affiliation. The cultures exhibited high resistance to gastroenterological stress (5 <= RD <= 10) and may be therefore recommended as:potential probiotics. PMID- 26263696 TI - [Yeasts of the Vineyards in Dagestan and Other Regions]. AB - Long-term studies of yeast species diversity in the vineyards of the Republic of Dagestan using various isolation techniques and various substrates in the vertical tier dynamics revealed 38 species. The most diverse species complex including -80% of the isolated species was formed on the berries. A list of 160 yeast species isolated from grapes, spontaneously fermented fresh juice, and other vineyard substrates was compiled using the results of the present work and the literature data on yeast occurrence. Analysis of generalized data revealed considerable similarity in the taxonomic composition of yeasts from different countries and continents and made it possible to shift from the genus to the species characterization of the grape-associated yeast community. PMID- 26263697 TI - [Activated Sludge Bacteria Transforming Cyanopyridines and Amides of Pyridinecarboxylic Acids]. AB - Species diversity of bacteria from the activated sludge of Perm biological waste treatment facilities capable of transformation of cyanopyridines and amides of pyridinecarboxylic acids was investigated. Enrichment cultures in mineral media with 3-cyanopyridine as the sole carbon and nitrogen source were used to obtain 32 clones of gram-negative heterotrophic bacteria exhibiting moderate growth on solid and liquid media with 3- and 4-cyanopyridine. Sequencing of the 16S rRNA gene fragments revealed that the clones with homology of at least 99% belonged to the genera Acinetobacte, Alcaligenes, Delftia, Ochrobactrum, Pseudomonas, Stenotrophomonas, and Xanthobacter. PCR analysis showed that 13 out of 32 isolates contained the sequences (-1070 bp) homologous to the nitrilase genes reported previously in Alcaligenes faecalis JM3 (GenBank, D13419.1). Nine clones were capable of nitrile and amide transformation in minimal salt medium. Acinetobacter sp. 11 h and Alcaligenes sp. osv transformed 3-cyanopyridine to nicotinamide, while most of the clones possessed amidase activity (0.5 to 46.3 mmol/(g h) for acetamide and 0.1 to 5.6 mmol/(g h) for nicotinamide). Nicotinamide utilization by strain A. faecalis 2 was shown to result in excretion of a secondary metabolite, which was identified as dodecyl acrylate at 91% probability. PMID- 26263698 TI - [Resistance of Various Yeast Ecological Groups to Prolonged Storage in Dry State]. AB - Resistance of 14 yeast species belonging to different ecological groups to extensive storage in a dried state was investigated. Pedobiotic yeasts isolated mainly from the soils of humid areas (Cryptococcus podzolicus, Cr. terricola, and Lipomyces starkeyi) were the least resistant. The yeasts associated with the nectar of entomophilous plants (Metschnikowia reukaufii and Candida bombi) also exhibited low resistance to drying. Complete death of these species occurred during the first month of storage. Eurybiotic species from various environments (Cryptococcus magnus, Cryptococcus victoriae, Debaryomyces hansenii, and Cryptococcus wieringae) were somewhat more resistant. Pigmented plant-associated yeasts (Rhodotorula mucilaginosa and Sporobolomyces roseus), as well as the pathogenic or opportunistic Candida strains (C. albicans and C. parapsilosis), were the most resistant to drying. Thus, occurrence of yeasts in natural habitats is closely associated with their ability to survive prolonged drying. PMID- 26263699 TI - [Active Sulfate Reduction in Acidic Sediments of Gold Mine Tailings]. PMID- 26263700 TI - [Session dedicated to neuromuscular channelopathies]. PMID- 26263701 TI - [Channels: a new way to revisit pathology]. AB - Many "essential" diseases that manifest themselves in the form of crises or fits (epilepsies, episodic ataxia, periodic paralyses, myotonia, heart rhythm disorders, etc.) are due to ionic channel dysfunction and are thus referred to as "channelopathies". Some of these disorders are congenital, due to mutations of genes encoding channel subunits, while others result from toxic, immune or hormonal disturbances affecting channelfunction. Channelopathies take on a wide variety of clinical forms, depending on the type of channel (sodium, potassium, calcium, chloride...) and the type of dysfunction (loss or gain of function). Some apparently unrelated diseases affecting distinct organs are due to a similar dysfunction of the same channel, revealing unsuspected relationships between organs and between medical specialties. In addition, a given syndrome can be caused by distinct channel dysfunctions. This provides new opportunities for diferential diagnosis and specific correction of the causal defects, although some treatments find applications across multiple medical specialties. PMID- 26263702 TI - [Lambert-Eaton myasthenic syndrome, an immune pathology of neuromuscular junctions]. AB - Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder affecting neuromuscular junctions. LEMS has served as a model of paraneoplastic neurological syndromes and antitumoral immunity, shedding light on the pathological role of autoantibodies directed against synaptic targets. Autoantibodies associated with LEMS are directed against voltage-gated calcium channels (VGCC) present on nerve terminals of neuromuscular synapses. Anti-VGGC antibodies play a direct pathological role in LEMS by blocking VGCC and calcium entry during depolarisation. Nearly half of patients with LEMS have small-cell lung cancer (SCLC), which also expresses VGCC. Diagnosis of LEMS frequently permits early detection and treatment of SCLC Knowledge of this syndrome has led to the discovery of a broad range of cancerous and non cancerous antibody mediated neurological syndromes, and led to the concept of autoimmune synaptopathies. PMID- 26263703 TI - [Congenital myasthenic syndromes; French experience]. AB - Congenital myasthenic syndromes CMS) form a heterogeneous group of genetic diseases characterized by abnormal neuromuscular transmission. The associated muscular weakness is exacerbated by exertion and usually starts during infancy/childhood In 2002 a national Congenital Myasthenic Syndromes Network was created in France, composed of neurologists, neuropediatricians, pathologists, molecular geneticists and neurobiologists. The network has now identified nearly 300 cases of CMS, as well as three new culprit genes. Based on our personal experience and data from the most recent studies, we describe the 18 principal culprit genes so far identified, along with diagnostic pitfalls, the disease course, prognosis and treatment. The underlying genetic defect remains to be identified in nearly half of CMS patients. PMID- 26263704 TI - [Ultraviolet A-induced DNA damage: role in skin cancer]. AB - Skin cancer is the most common human malignancy, and sunlight exposure is known to play a role in its genesis. Ultraviolet B (UVB) (300-320 nm) has long been considered responsible for the skin damage underlying these cancers, whereas the toxicity of UVA (320-400 nm) has been largely overlooked The intimate mechanisms of photocarcinogenicity remain poorly understood, but UV-induced DNA damage appears to be a major initiating event. Cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) photoproducts (6-4PPs) are the main dimeric lesions induced by UVB, whereas the genotoxic effects of UVA have long been attributed to oxidative damage, the main lesion being the oxidized base 8-oxo-7,8dihydroguanine (8 oxoGua). However; powerful new techniques for analyzing DNA damage (the Comet assay, and especially HPLC-MSIMS) have demonstrated that UVA irradiation mainly triggers the formation of CPDs, especially CPD-TT both in cell models and in total human skin. A direct photochemical process is currently thought to account for CPD induction by UVA. The multilayer structure of the epidermis protects against UVB-induced dipyrimidine lesions in total skin but offers only weak protection against UVA. In addition, repair efficiency is undermined by UVA. CPDs, the main DNA lesions induced by UVA in total skin (which is more permeable to UVA), are inefficiently repaired CPDs have strong mutagenic potential, and recent studies clearly show that CPDs, rather than 8-Oxo-Gua, are the main mutagenic photoproducts induced by UVA. The UV signature of induced mutations is characterized by transitions from C to T or CC to TT in dipyrimidine sequences. These mutations target the p53, patched 1 and SMO genes in carcinomas, and the PTEN RAC1, PPP6C, STK19 and PPP6C genes in melanomas of exposed skin. UVA also mainly induces CPDs in melanocytes, in amounts similar to those observed in keratinocytes, demonstrating that melanin does not prevent CPD formation. In contrast, UVA induces far more abundant 8-oxo-Gua production in melanocytes than in keratinocytes. Thus, under UVA irradiation, oxidative stress contributes more to DNA damage in melanocytes than in keratinocytes. In addition, baseline oxidative damage (in the absence of UVA) is already higher in melanocytes. The photosensitizer may be melanin itself. This is supported by a recent study based on a murine model, in which melanoma induction was shown to require both UVA and the presence of melanin in melanocytes, and is associated with oxidative damage to DNA. Conversely, UVB was found to initiate melanoma through a direct, pigment independent pathway. Thus, two wavelength-dependent pathways can induce melanoma, with melanin playing an unexpected role. Constitutive pigmentation is very effective in preventing UV-induced damage, and a clear correlation can thus be found between, on the one hand, the amount of CPD TT produced by both UVB and UVA and, on the other hand, the minimum erythematous dose and the phototype. Melanin is thus a two-facetted molecule, protecting the skin when its synthesis is complete and when melanosomes take on their nucleus-protective geometric configuration in keratinocytes, but having a pro-oxidant action when only partially polymerized and exposed to UV Repeated exposure of volunteer skin shows that a tan induced by UVB provides little protection against DNA damage caused by subsequent exposure, while tanning with UVA provides no protection at all. Yet both UVB and UVA provoke DNA damage. All these recent data highlight the potential role of UVA in skin carcinogenesis, and reinforce epidemiological studies showing an increased risk of melanoma among users of tanning lamps, particularly young women. The decision by the International Agency for Research on Cancer to classify UVA and tanning devices as group 1 carcinogens, and the opinion issued by the French National Academy of Medicine on tanning booths, therefore appear to be fully justified. The use of tanning salons should be permanently banned PMID- 26263705 TI - [Drug therapy of melanoma: anti-CTLA-4 and anti-PD-1 antibodies]. AB - Management of patients with metastatic melanoma has improved radically in recent years with the development of new drugs capable of signifcantly prolonging life expectancy. Two strategies have been implemented: targeted anti-BRAF therapy for BRAF-mutated melanomas, and non specific immunotherapies based on anti-CTLA-4 (ipilimumab) and, more recently, anti-PD-1 monoclonal antibodies. These antibodies, by blocking physiological brakes on immune activation, induce an indirect immune response. Ipilimumab, a drug approved in 2011 is of benefit to 20 % of patients but can also trigger significant immune-mediated toxicity. Anti-PD 1 antibodies presently in development seem to have a better therapeutic index, with higher response rates and less toxicity than ipilimumab. Combination therapy with anti-CTLA-4 and anti-PD-1 v is also giving encouraging preliminary results. In future, these new drugs will probably be used in combination, either concurrently or sequentially. PMID- 26263706 TI - [Melanoma: Cellular and vaccinal immunotherapy]. AB - Melanoma is a malignancy in which the immune system plays a central role, thus explaining the effectiveness of therapeutic vaccination and cellular immunotherapy with tumor-infiltrating lymphocytes. The identification of specific melanoma antigens was an important step in the development of these new approaches. These treatments are capable of yielding tumor responses that last several years, but the response rate is currently inadequate. The crucial role of the tumor microenvironment has recently been shown: melanoma cells render their immediate environment immunotolerant, undermining the effectiveness of stimulated cytotoxic T lymphocytes. The mechanisms responsible for this state of immune tolerance are a major focus of research. Current therapeutic strategies are based on early adjuvant approaches, destruction of regulatory T cells by lymphodepletion prior to immunotherapy, selection of the melanoma antigens inducing the best cytotoxic T cell responses, and combining cellular therapy with monoclonal antibodies that block molecules inhibiting T lymphocyte activation. Immune therapy for melanoma is thus moving towards adjuvant strategies for early stage disease and combined treatments for metastatic melanoma. It is also important to identify markers that can be used to predict which patients will respond to a given treatment. PMID- 26263707 TI - [Future targeting of the RAS/RAF/MEK/ERK signaling pathway in oncology: the example of melanoma]. AB - The proliferation, survival and mobility of cancer cells are maintained by deregulation of signaling pathways, including RAS/RAF/MEK/ERK/. Constitutive activation of these pathways is a common event in human cancers. It is most often caused by mutations or altered expression of genes encoding key players in this pathway. Knowledge of the mechanisms of intracellular activation of these circuits has led to the development of inhibitory molecules aimed at limiting tumor growth. These molecules have been developed through extensive clinical trials marked by impressive therapeutic successes that have pioneered the concept of targeted therapies, leading to a new paradigm of cancer therapy. However, despite these remarkable clinical responses, particularly in metastatic melanoma, poorly understood drug resistance mechanisms eventually come into play. Resistance mechanisms associated with secondary mutations in B-RAF seem to be infrequent in melanomas, while those related to target circumvention are more common. The latter include an increase in the expression and regulation of PDGF and IGF-l receptors, and secondary mutations in the N-RAS, COT or MEK genes. They involve the activation pathways MEK/ERK and/or PI3K/AKT in conditions in which the target is inhibited. Resistance may also be explained by deregulation of the MEK/ERK pathway, leading to the expression of genes that had been subject to negative feedback. Moreover, the tumor microenvironment, through the secretion of soluble factors, stimulates signaling pathways that can compensate for MEK/ERK pathway inhibition. Lastly, combinations of MEK/ERK inhibition and immunotherapy open the way to new therapeutic strategies designed to circumvent drug resistance. Without calling into question the concept of "oncogenic addiction", in which alteration of a single gene is responsible for persistence of the tumoral phenotype, these findings call for a rethink on the use of targeted therapies. A more integrated view of the tumor including its microenvironment, will no doubt be necessary. PMID- 26263708 TI - [Renal tubular dysgenesis and mutations in the renin-angiotensin system genes]. AB - Renal tubular dysgenesis is a severe disease characterized by the absence of differentiated proximal tubules, leading to fetal anuria and persistent oligohydramnios. The absence of amniotic fluid results in a series of malformations, including facial dysmorphia, limb deformation and also lung hypoplasia, leading to respiratory distress at birth. The disease is linked to mutations in the AGT, REN ACE andAGTR1 genes that compose the renin-angiotensin system (RAS). The absence of functional RAS leads to fetal and neonatal hypotension, renal hypoperfusion, and tubular dysgenesis. The use of cellular models expressing these mutations has advanced our understanding of the structure function relationship of RAS proteins, notably by showing that defective misfolded proteins undergo either intracellular accumulation and retention, or rapid degradation. Moreover, these studies confirm that ACE has to be inserted in the plasma membrane to be active. PMID- 26263709 TI - [Combined blockade of the renin-angiotensin system]. AB - Blockade of the renin-angiotensin system (RAS) with angiotensin-converting-enzyme (ACEI) inhibitors or angiotensin II receptor blockers (ARB) has become a major therapeutic tool. Due to internal counter-regulation, however, this system cannot be fully blocked by targeting only one of its components. Instead of increasing the doses of an ACEI, an ARB or a renin inhibitor, blocking RAS at two successive levels neutralizes the consequences of internal counter-regulation and thus provides a more complete blockade with more pronounced biological effects. Additive effects on blood pressure lowering and on renin secretion during combined administration of RAS blockers were first demonstrated in normotensive subjects and in various experimental models of hypertension, heart failure and renal failure. Although combined RAS blockade provided an additional hemodynamic response and more complete neutralization of the cellular effects of angiotensin II, no benefit was observed in terms of cardiovascular or renal protection in heart disease (heart failure, post-myocardial infarction, high vascular risk) or kidney disease (diabetic nephropathy). Moreover, more complete RAS blockade is risky in conditions where blood pressure and renal perfusion are renin-dependent (renal failure and hypotension) and also in hypoaldosteronism (hyperkalemia). The European, French and US. health agencies have contraindicated combined RAS blockade because of its unfavorable risk-benefit balance, especially in patients with diabetes or renal failure. PMID- 26263710 TI - [Organized breast cancer screening]. AB - Breast screening programs are increasingly controversial, especially regarding two points: the number of breast cancer deaths they avoid, and the problem of over-diagnosis and over-treatment. The French national breast cancer screening program was extended to cover the whole country in 2004. Ten years later it is time to examine the risk/benefit ratio of this program and to discuss the need for change. Like all forms of cancer management, screening must be regularly updated, taking into account the state of the art, new evidence, and uncertainties. All screening providers should keep themselves informed of the latest findings. In the French program, women aged 50-74 with no major individual or familial risk factors for breast cancer are offered screening mammography and clinical breast examination every two years. Images considered non suspicious of malignancy by a first reader are re-examined by a second reader. The devices and procedures are subjected to quality controls. Participating radiologists (both public and private) are required to read at least 500 mammographies per year. The program's national participation rate was 52.7 % in 2012. When individual screening outside of the national program is taken into account (nearly 15 % of women), coverage appears close to the European recommendation of 65 %. Breast cancer mortality has been falling in France by 0.6 % per year for over 30 years, starting before mass screening was implemented, and by 1.5 % since 2005. This decline can be attributed in part to earlier diagnosis and better treatment, so that the specific impact of screening cannot easily be measured. Over-treatment, defined as the detection and treatment of low-malignancy tumors that would otherwise not have been detected in a person's lifetime, is a major negative effect of screening, but its frequency is not precisely known (reported to range from 1 % to 30 %). In view of these uncertainties, it would be advisable to modify the program in order to increase its efficiency, by targeting populations at a higher risk than the women currently included, and to reduce the number of mammograms done outside the program, as they are not subject to the same quality controls. Risks could be reduced by increasing the sensitivity of mammography and the specificity of the readings. Moreover, it is mandatory to inform women of both the benefits and risks of screening, in compliance with the principle of enabling patients to make a free and informed choice. PMID- 26263712 TI - Urgent Care Facilities: Geographic Variation in Utilization and Charges for Common Lab Tests, Office Visits, and Flu Vaccines. AB - The rapid growth of urgent care facilities (UCFs) and other types of convenient care centers has largely been attributed to increasing consumer demand for more convenient and affordable healthcare. UCFs typically treat non-emergency, acute conditions and are increasingly serving as an alternative to "traditional" care settings, such as physician offices and emergency departments (EDs). A study was conducted to characterize geographic variation in both utilization and charges for common lab tests, office visits, and flu vaccines by care settings. Based on claims data from FAIR Health's National Private Insurance Claims (FHNPIC) database, the results suggest that utilization and charge patterns for common procedures vary significantly by care setting across geographic region and over time but the variations are generally small in magnitude. For example, across geographic regions, charges for the flu vaccine are found to be higher when performed in a physician's office in contrast to being performed in a UCF. PMID- 26263711 TI - [Organized colorectal cancer screening]. AB - Organized colorectal screening in France was extended to the whole of the country in 2008. People aged from 50 to 74 years are offered fecal occult blood tests (FOBT) every two years. Patients with individual or familial risk factors for colorectal disease are excluded from the program. Despite promotion campaigns, the participation rate remains low, at about 30 %. It has been decided that a quantitative immunogical test will replace FOBT in the near future. The evaluation and use of colonoscopy and recto-sigmoidoscopy as screening tests must be re-evaluated in the light of recent research findings. PMID- 26263713 TI - Clinical Characteristics and Outcomes of Patients with Intracerebral Hemorrhage after Interhospital Transfer to a Designated Stroke Center. AB - Patients with acute ischemic stroke have improved outcomes when cared for in designated stroke centers (SC), in part due to enhanced thrombolytic use. Whether patients with intracerebral hemorrhage (ICH) also benefit from SC care is unknown. In this study, we compared the clinical characteristics and outcomes of ICH patients who underwent interhospital transfer (IHT) to a Joint Commission (JC) designated SC, to ICH patients who presented directly to the SC's emergency department (ED). METHODS: Patients with ICH admitted between 2006 and 2013 were evaluated. The primary outcome measure was in-hospital death or hospice. RESULTS: Among 760 consecutive admissions for ICH, 321 (42.2%) were IHTs. There has been a 30% annual increase in IHT of ICH patients since 2006. The IHT group was younger (70.26 vs 72.28; P =.055), had lower ICH scores (P = .007), a higher Glasgow Coma Scale (GCS) (P = .037), and lower systolic blood pressure (SBP) (P = .003) than those arriving directly to the ED. Female sex was a predictor of in-hospital mortality (OR = 2.26). CONCLUSION: IHT is increasingly common for patients with ICH. The benefit of transfer remains unclear, as younger, healthier patients were the most likely to be transferred. Comprehensive stroke registries are needed to determine if outcomes differ for ICH patients based on transfer or SC care. PMID- 26263715 TI - Unusual Case of Isolated Pleural B-Cell Lymphoma. AB - Pleural involvement in lymphoma is rare as the initial presentation of disease in the immunocompetent patient. We describe a rare case of primary, isolated pleural B-cell lymphoma in a 75-year-old female, previously treated for adenocarcinoma of the left lung with lobectomy and chemotherapy, who presented with shortness of breath. A CT scan of the chest revealed a right-sided pleural effusion and pleural thickening. She underwent multiple nondiagnostic thoracenteses. A subsequent surgical biopsy was diagnostic of large B-cell lymphoma. PMID- 26263714 TI - Levamisole-Induced Vasculitis with Renal Involvement. AB - A significant amount of cocaine used in the United States today is adulterated with levamisole. In some instances, prolonged use of contaminated cocaine is associated with the development of levamisole-induced vasculitis (LIV) with features of cutaneous vasculitis and agranulocytosis along with other constitutional symptoms and arthritis. We describe a case of a crack cocaine user with LIV, who developed significant renal disease secondary to crescentic glomerulonephritis, confirmed on renal biopsy. Renal vasculitis is an uncommon feature of LIV and significantly affects clinical course and management. PMID- 26263716 TI - An Adverse Electrophysiological Interaction Between an Implantable Cardioverter Defibrillator and a Ventricular Assist Device. AB - Many patients with left ventricular assist devices (LVAD) have implantable cardioverter defibrillators (ICDs) as part of the management of advanced heart failure. With increasing use and coexistence of these devices in patients with advanced cardiomyopathy, adverse interactions between these devices have been recognized. We herewith describe a rare adverse interaction of electromagnetic interference (EMI) between a third-generation, continuous-flow device (The HeartWare HVAD) and an ICD which resulted in the delivery of inappropriate ICD therapies. A schematic approach for the prevention and treatment of electromagnetic interference has also been described. PMID- 26263718 TI - Surgical Quality Initiatives in Connecticut: We Are Building a Cathedral. PMID- 26263717 TI - Annual State of Connecticut Obstetrics and Gynecology Resident Research Day. AB - To increase opportunities for Obstetrics and Gynecology(Ob/Gyn) residents to present their research, an Annual State of Connecticut Ob/Gyn Resident Research Day (RRD) was created. At the first annual RRD, 33 residents, representing five of six Connecticut Ob/Gyn residency programs, presented 39 poster and eight oral presentations. RRD evaluators rated the overall symposium and the quality of resident oral and poster presentations as either "excellent" or "above average." Residency program directors reported that the symposium was "very helpful" for evidencing resident scholarship as required by the Accreditation Council for Graduate Medical Education (ACGME). Surveyed residents reported that the symposium promoted their research and was a valuable investment of their time. An annual specialty-specific, statewide RRD was created, experienced good participation, and was well evaluated. The annual, statewide Ob/Gyn RRD may serve as a model for development of other specialty-specific, statewide RRD events. PMID- 26263719 TI - Aporia in Medicine. PMID- 26263720 TI - Donning Your Detective Hat: A Med Student's Path to Research. PMID- 26263721 TI - Unwittingly Imparted. PMID- 26263722 TI - 50 YEAR AGO--From Connecticut Medicine. THE PRESIDENT'S PAGE. The 173rd Annual Meeting Of The Connecticut State Medical Society. 1965. PMID- 26263723 TI - 50 YEARS AGO--From Connecticut Medicine. THE PRESIDENT'S PAGE. Utilization--The Physician's Problem. 1965. PMID- 26263724 TI - The Connecticut Healthcare Landscape: The Borgias and Cuckoo Clocks. PMID- 26263725 TI - A Call to Action. PMID- 26263728 TI - BURIED ALIVE. Essential rescue skills are important. PMID- 26263726 TI - Tipping Point: What I Have Learned Since the Last Time We Met. PMID- 26263731 TI - EDITOR-IN-CHIEF A.J. HEIGHTMAN, MPA, EMT-P, RESPONDS. PMID- 26263733 TI - LATE FEE. What does it take to be an innovator?. PMID- 26263734 TI - RAPID DECLINE. What causes this patient to return to the ambulance for a second assessment?. PMID- 26263735 TI - DNR CONFUSION. POLST interpretation lacks consensus among prehospital providers. PMID- 26263736 TI - UNTANGLING METAL. The EMT's & paramedic's role in vehicle extrication. PMID- 26263737 TI - SUSPENSION SHOCK. Redefining the diagnosis & treatment of suspension trauma. PMID- 26263738 TI - GLOBAL COMMUNITY MEDICS. Profiles of international mobile integrated healthcare initiatives. PMID- 26263739 TI - FACE TO FACE. The gruesome reality of facial trauma. PMID- 26263740 TI - INSPIRATION. The story of one medic's miraculous recovery. PMID- 26263741 TI - MAINTAINING CREDENTIALS. Staying proficient in clinical decision-making & skills. PMID- 26263742 TI - AS SEEN ON TV. CPR's unrealistic portrayal on the small screen. PMID- 26263743 TI - Conversations key to adopting clinical change. PMID- 26263744 TI - Biosimilars: Good News, But Not The New Generics. PMID- 26263745 TI - A Case For Integrated Care In Senior Living. PMID- 26263746 TI - Dementia Care, Outpatient Therapy Popular Services. PMID- 26263747 TI - 2015 Year Of The Mergers. PMID- 26263748 TI - The impending burden of kidney disease. PMID- 26263749 TI - Protein in our food. How much is too much, and should we worry about the phosphorus? PMID- 26263750 TI - The chronic disease self-management program--A pilot study in patients undergoing hemodialysis. AB - A strong emphasis on self-management for health maintenance in a variety of chronic diseases has been shown to benefit patients' outcomes and quality of life. However, little has been published on such programs in patients with chronic kidney disease. We studied the feasibility and effectiveness of the Chronic Disease Self-Management Program (CDSMP) in 14 patients with ESRD undergoing conventional hemodialysis. This program is designed to enhance skills in the areas of medical, emotional, and role management. Outcome measures in health status, self-management behaviors, self-efficacy, and health care utilization were evaluated through use of questionnaires at baseline and after six months. PMID- 26263751 TI - Rules on authority vary by state. PMID- 26263752 TI - A life of service. Maggie Colin looks back at 51 years as a dialysis nurse. PMID- 26263753 TI - Trends in Social Work. Nephrology social work meets integrated care: A partnership for the road ahead. AB - Integrated care has brought changes to the field of nephrology social work. In turn, nephrology social work has brought innovative contributions to the field of integrated care. The new social work service delivery systems described in this article are sure to help the industry reach its goals to keep care patient centered while maintaining quality and reducing the costs of treating end stage renal disease. Social workers are called to serve the needs of the client, the family, the community and the society at large. Nephrology social workers are right where they belong in the ESRD integrated care environment. They feel right at home. PMID- 26263754 TI - SCM15/Council of Advanced Practitioners. The cost of infections for patients and providers. PMID- 26263755 TI - SCM15/Council of Nephrology Social Workers. Hospice, dialysis, and health care reform. PMID- 26263756 TI - NKF SCM15 Physicians Program. Update on advances in PD. PMID- 26263758 TI - [Molecular mechanisms of catalytic reactions and superoxide production by cytochrome bc1 complex]. AB - Cytochrome bc1 is one of the key enzymes of biological energy conversion. The enzyme couples electron transfer between membranous quinones and water-soluble cytochromes with proton translocation across the membrane contributing to generation of protonmotive force used for ATP synthesis. This process involves the action of two types of quinone-binding catalytic sites localized on two opposite sides of the membrane. One of them catalyzes the unique in biology bifurcation reaction that directs electrons coming from quinol into two separate chains of cofactors. Side reactions of bifurcation may lead to generation of superoxide. The enzyme is a homodimer in which each monomer is equipped with a set of both catalytic sites. Recent studies identified spectroscopically a state that can be assigned as an intermediate of bifurcation reaction, described conditions of superoxide generation, and also demonstrated existence of inter monomer electron transfer. These findings shed light on our understanding the molecular mechanisms of catalytic and side reactions and functioning of cytochrome bc1 as dimer in the context of cell physiology. PMID- 26263759 TI - [RNA processing - unusual mechanism of generation of novel classes of noncoding RNAs from functional RNAs]. AB - Non-coding RNAs (ncRNAs) play regulatory roles at all stages of the genetic information transmission from DNA to proteins. The ncRNA-mediated mechanisms leading to specific expression or silencing of particular genes seem to be of special importance. In addition to well-known and well-understood functions of RNAs, we recently discover new and nonobvious aspects and possibilities of regulating cellular processes. One example is the processing of various RNAs, the mechanism of formation of short non-coding RNAs from existing functional RNAs. Both: the sources of these short RNAs and the functions performed by them are diverse. Their presence greatly enriches the possibilities of gene expression regulation, as it turns out, at all stages. PMID- 26263760 TI - [cAMP cascade in regulation of protein glycosylation]. AB - O- and N-glycosylation are the most common and complex of the post-translational modifications. Both are enzymatic processes and it was suggested that both could be regulated by cAMP cascade at the early stages. N-glycosylation starts with the formation of lipid-linked oligosaccharides and this process is catalysed by crucial glycosyltransferase - dolichol phosphate mannose synthase. The results of several studies strongly suggest that the cAMP acting through a cAMP-dependent protein kinase A-mediated protein phosphorylation/dephosphorylation cycle may modulate activation of this enzyme. It was shown that cAMP can also up regulate another enzyme involved in phosphodolichole synthesis - cis-prenyltransferase. The mechanism acting here is the alteration of the rate of its gene expression. cAMP cascade is also involved in regulation of O-glycosylation since phosphorylation of human glutamine:fructose-6-phosphate amidotransferase results in depletion of O-GlcNAc structure formation. These observation suggested an important role of GPCRs and their ligand in regulation of N- and O-glycan synthesis. PMID- 26263761 TI - [The role of ATM kinase in neurodegeneration]. AB - Neurodegenerative diseases represent a major challenge for modern medicine. Despite many years of research, no effective neuroprotective therapy has been proposed. Ataxia telangiectasia (A-T) is rare disease, which is caused by a mutation of the ATM protein. Cerebellar degeneration is the main symptom of the A T. The kinase ATM, inter alia is involved in the repair of DNA damage, cell cycle regulation and the control of apoptosis. In recent years the presence of that kinase in the cytoplasm has been demonstrated. This led to the discovery of its participation in the regulation of metabolic processes, homeostasis mitochondrial oxidative stress response or modulation of synaptic function. The pleiotropic effect of ATM kinase requires effective control exercised by, inter alia, proteins having specific binding motifs this kinase, such as ATMIN and NBS1. The regulation of prosurvival processes which are controlled by ATM kinase, may prove an attractive therapeutic strategy in treatment of neurodegenerative diseases. PMID- 26263762 TI - [The role of actin cytoskeleton and myosin VI in clathrin-dependent endocytosis]. AB - Myosin VI (MVI), an actin-based molecular motor, is believed to have unique functions in eukaryotic cells, because it is the only myosin shown to move toward the pointed end of actin filaments, in the opposite direction of all other myosins. Given some unusual structural and kinetic properties of MVI, many models of its functioning in variety cellular processes have been proposed, and one of them is endocytosis. Different roles for many proteins associated with endocytic domains, such as clathrin or dynamin, have been defined. However, some results provide compelling evidence that actin filaments and MVI are both involved in two distinct steps of clathrin-dependent endocytosis: the formation of clathrin coated vesicles and the movement of nascent uncoated vesicles from the actin-rich cell periphery to the early endosome. There are several postulated mechanisms of function for actin cytoskeleton and MVI during subsequent steps of clathrin dependent endocytosis. Below we focus on their potential roles in this cellular process. PMID- 26263763 TI - [Comparison of apoptosis in vertebrates and invertebrates (mainly in insects) with particular emphasis on physiological role of this process in development of organisms]. AB - Apoptosis (from Greek "dropping off leaves") is defined as active genetically programmed cell death, that may occur in single cell or group of cells in organisms. This process is highly conserved among invertebrates and vertebrates but we can identify different components of the apoptotic pathways or changes in mechanisms by which apoptosis is activated between species. Generally apoptosis plays a key role in normal tissue development as well as in elimination of unwanted cells including damaged or infected cells. This type of cell death, conserved through evolution, permits homeostasis maintenance on the right level. The mechanisms of apoptosis are very complex and sophisticated, in vertebrate research indicates a few main pathways, differing in the first stage leading to the activation of executive enzymes - caspases. Caspases are essential for the initiation and regulation of apoptosis and a large number of these enzymes have been identified in various animals from sponges to vertebrates. In these work we focused on comparison invertebrate and vertebrate pathways of apoptosis, especially in insects species (Diptera and Lepidoptera). We investigate how these organisms use that kind of cells control as kind of immune response triggered by pathogen infection. PMID- 26263764 TI - [Plant signaling peptides. Small post-translationally modified peptides]. AB - Recent genetic, bioinformatic and biochemical analyses have revealed that many secretory peptides are important components in intercellular signaling that coordinate and specify cellular functions in plants. The signaling peptides discovered in plants thus far can be considered to fall into two broad groups. Peptides from the first group are undergo post-translational modification, such as proline hydroxylation, hydroxyproline arabinosylation or tyrosine sulfation. Peptides from the second group are defined as cysteine-rich peptides (CRPs). The Cys-rich peptides are larger and they contain 4 to 16 cysteine residues. In parallel with the discovery of plant signal peptides, specific receptors for such peptide signals are identified. So far, the receptors for plant peptides that have been identified are members of the receptor-like kinases (RLKs) and the receptor-like proteins (RLPs) families, and most of them contain leucine-rich repeat (LRR) extracellular domain. The present review presents the recent progress in research on small post-translationally modified signal peptides. Recent findings indicate that these peptides are involved in various aspects of plant growth regulation including meristem organization, primary root development, lateral root initiation, vasculature development, organ abscission, and root nodulation. PMID- 26263765 TI - [Photodynamic reaction and oxidative stress - influence of the photodynamic effect on the activity antioxidant enzymes]. AB - The interaction of light with a photosensitizer, accumulated in a tissue in the presence of oxygen, leads to formation of reactive oxygen species, mainly of singlet oxygen and free radicals. These factors react with biomolecules producing their oxidized states. Reactive oxygen species, such as singlet oxygen and free radicals are able to damage membranes, DNA, enzymes, structural peptides and other cellular structures leading to cell death. An antioxidant protection of cell is formed by enzymes belonging to the family of oxidoreductases: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR). Photodynamic therapy leads to the increased production of oxidizing toxic forms. It is important to analyze impact of PDT on the activity of antioxidant enzymes, such as SOD, CAT, GPx. The activity of antioxidant enzymes during the photodynamic effect is influenced by both the light energy dose and the concentration of photosensitizer. The presence only of the photosensitizer or only the light energy may also result in changes in the activity of these enzymes. The differences in changes in the activity of these enzymes depend on the type of used photosensitizer. A phenomenon of selective accumulation of photosensitizer in tumor tissues is used in the photodynamic method of tumor diagnosis and treatment. PMID- 26263766 TI - [The effects of selenium deficiency in animals]. AB - All mineral elements have their place in nature as macroelements, microelements and submicroelements. They should be delivered to the organism in the proper composition and amount and in the form easy assimilated by the organism. Creating the food composition we should take into account not only energy metabolism and digestible protein content, but also the content of minerals components, among them of selenium. Selenium is assimilated by the organism in the form of selenomethionine and selenocysteine as well as certain inorganic compounds. This element in the excess is a poison, but on the other hand it is essential food component, because of its roles in the metabolism, as well as anticancer factor and antioxidant. PMID- 26263767 TI - [Overview of methods used for determination of selected sphingolipids in different biological materials]. AB - Sphingolipids are bioactive molecules, which constitute part of the cell membrane. They are involved in signaling and regulation of many cellular processes including cell growth and proliferation, apoptosis, angiogenesis or inflammatory processes. Several methods were described to determine the concentration and conversion of sphingolipids including radioactive labeling, enzymatic methods, MS, RP-HPLC, ESI LC-MS/ MS, UPLC-MS/MS. The development and validation of analytical and extraction methodology for the determination of selected sphingolipids in various biological materials are described in this paper. PMID- 26263768 TI - [Current situation of soil-transmitted nematodiasis monitoring in China and working keys in future]. AB - Soil-transmitted nematodiasis is widely epidemic in rural areas in China. It was showed that the infection rate of soil-transmitted nematodes was 19.56% while the overall number of persons infected was 129,000,000, which was supported by the results of the National Survey of Current Situation of Major Human Parasitic Diseases in China in 2005 published by former Ministry of Health. Therefore, soil transmitted nematodiasis was included in the national infectious diseases and pathogenic media monitoring system by Chinese Center for Disease Control and Prevention in 2006, and subsequently 22 monitoring spots were established nationwide. From 2006 to 2013, the human infection rate of intestinal nematodes in national monitoring spots decreased from 20.88% to 3.12%, which showed a declining trend year by year. Meanwhile, the infection rates of Ascaris lumbricoides, Trichuris trichiura, hookworm, Enterobius vermicularis decreased from 10.10%, 5.88%, 8.88%, 10.00% in 2006 to 0.76%, 0.42%, 2.04%, 6.78% in 2013 respectively. In this paper, the current situation of soil-transmitted nematodiasis is overviewed based on a summary of the 8 years' monitoring work, as well as the experiences, challenges and key of monitoring work in the future. PMID- 26263769 TI - [Evaluation of effectiveness of comprehensive schistosomiasis control project in Yunnan Province from 2004 to 2013]. AB - OBJECTIVES: To evaluate the effect of comprehensive schistosomiasis control project in Yunnan Province after its implementation for ten years, so as to provide the evidence for formulating the future prevention and control strategy. METHODS: The data of the schistosomiasis comprehensive control project and the endemic situation were collected and analyzed to evaluate the control effect of the project in Yunnan Province from 2004 to 2013. RESULTS: After the comprehensive control project implementation for ten years, the Oncomelania hupensis snail area in Yunnan Province decreased from 4,364.79 hm2 in 2004 to 1,528.50 hm2 in 2013, with a reduction rate of 64.98%, and the occurrence rate of frames with snails and the density of living snails decreased from 4.71% and 0.26 snails/0.1 m2 in 2004 to 1.35% and 0.04 snails/0.1 m2 in 2013, with the reduction rates of 71.34% and 84.62%, respectively. The schistosome infected snails were found only in 2011 and 2013 since 2008. In 2013, the infection rates of human (0.0021%) and cattle (0.0209%) decreased by 99.84% and 99.44%, respectively, compared to those in 2004, and no acute schistosome infection cases were found since 2008. The 212 villages with relatively serious endemic situation (Type One, Type Two and Type Three) all declined to the slight endemic villages (Type Four and Type Five), therefore, they reached the criteria of schistosomiasis transmission controlled or interrupted. The awareness rates of schistosomiasis control among villagers and students in endemic areas were above 90% and 98%, respectively. CONCLUSION: The effect of the comprehensive schistosomiasis control project is significant in Yunnan Province, but the task to consolidate and enlarge the control results still remains a challenge. PMID- 26263770 TI - [Spatiotemporal pattern of Oncomelania snails at village level in Hubei Province]. AB - OBJECTIVE: To study the spatiotemporal distribution of Oncomelania hupensis snails in different areal-types at a village level in Hubei Province, so as to provide the basis for formulating the strategies and measures of snail control. METHODS: The snail data of 30 schistosomiasis epidemic counties at a village scale in Hubei Province from 2007 to 2012 were collected and combined with the geographic information of each village to construct the spatial database of snails. The snail area and its change trend of different areal-types were illustrated; the multilevel model of snail distribution was established. RESULTS: The snail area of each village from 2007 to 2012 was correlated (Intra-class correlation coefficient, ICC = 95.7%). Both the baseline and the rate of change of snail area were significantly different (sigma(2)(u0) = 4,766.53, sigma(2)(u1)= 20.96, both P < 0.01). The rate of change of snail area was higher if the baseline of snail area was higher (sigma(2)(u01) =126.78, P < 0.01). The snail areas of villages were increased slowly by year (year = 0.64,P < 0.01). The average snail areas and growth of snail areas of villages in the marshland and lake region were largest (type= -29.84, P < 0.01; year*type = -0.52, P < 0.01). CONCLUSIONS: The snail area is significantly different among both villages and areal-types. This study spatially visualizes the snail data of 30 schistosomiasis epidemic counties in Hubei Province and establishes the multilevel model, providing the basis of snail control in different areal-types. PMID- 26263771 TI - [Spatial regression analysis of relationship between schistosome infection rate of Oncomelania hupensis snails and climate factors]. AB - OBJECTIVE: To explore the relationship between the schistosome infection rate of O. hupensis snails and the climate factors in endemic areas of schistosomiasis, so as to provide the evidence for improving the snail control. METHODS: The snail and climate data of 18 counties in Hubei Province in 2009 were collected to obtain the infection rate of O. hupensis snails and to fit the spatial regression models. RESULTS: The multiple linear regression model showed that the residuals were autocorrelated (Moran's I = 0.182 8, P < 0.01) and the spatial regression was necessary. The spatial lag model (SLM) was selected according to the results obtained by Lagrange multiplier statistics. The spatial parameter rho of SLM was significant (p= - 0.151 5, P < 0.05) and the infection rate of O. hupensis snails was positively correlated with the annual average temperature (P < 0.05). The correlations between the infection rate of O. hupensis and the annual average relative humidity, precipitation and sunshine duration were not significant respectively (all P > 0.05). CONCLUSIONS: The spatial regression models could be well applied in the analysis of the relationship between the O. hupensis snails and climate factors. The annual average temperature is the primary climate factor influencing the infection of O. hupensis snails. PMID- 26263772 TI - [Molluscicidal effect of 5% powder of niclosamide ethanolamine salt granules (NEG) in field of mountainous areas in Yunnan Province]. AB - OBJECTIVE: To evaluate the molluscicidal effect of 5% powder of niclosamide ethanolamine salt granules (NEG) in the field of mountainous areas in Yunnan Province. METHODS: The grasslands with Oncomelania hupensis snail habitats were chosen in Beideng Village, Heqing County, Yunnan Province, and were divided into 7 groups (groups of NEG 30 g/m2, NEG 40 g/m2, NEG 50 g/m2, NEG 40 g/m2 plus obstacle clearing, 50% niclosamide ethanolamine salt wettable powder (WPN) 6 g/m2, WPN 6 g/m2 plus obstacle clearing, and fresh water). The snail death rates and the densities of living snails were investigated and the results were compared in the different groups 7 d, 15 d, and 30 d after the implementation. RESULTS: Seven d, 15 d, and 30 d after the implementation, the snail death rates of the groups of NEG 30 g/m2, 40 g/m2, and 50 g/m2 were from 72.75 % to 95.83%, and the average descent rates of living snail densities were from 72.26% to 95.54%. Seven d, 15 d, and 30 d after the implementation, in the NEG 40 g/m2 group, the snail death rates were from 81.69% to 87.19%, and the average descent rates of living snail densities were from 81.42% to 87.91% ; in the NEG 40 g/m2 plus obstacle clearing group, the snail death rates were from 84.89% to 88.24% and the average descent rates of living snail densities were from 85.63% ~ 88.22%; in the WPN 6 g/m2 group, the snail death rates were from 85.23% to 86.17% and the average descent rates of living snail densities were from 85.76% to 86.05%; in the WPN 6 g/m2 plus obstacle clearing group, the snail death rates were from 88.89% to 92.10% and the average descent rates of living snail densities were from 86.71% to 92.20%. The obstacle clearing improved the molluscicidal effect. CONCLUSION: NEG has a good molluscicidal effect in the field of mountainous areas in Yunnan Province. PMID- 26263773 TI - [Preliminary study on pro-apoptotic gene BAD of Schistosoma japonicum]. AB - OBJECTIVE: To understand the characteristics of pro-apoptotic gene SjBAD of Schistosoma japonicum, such as its biology, immunology, and transcriptional expression, and evaluate its potential of the recombinant protein as a vaccine candidate for schistosomiasis. METHODS: SjBAD was amplified by PCR and subeloned into a pET-28a(+) vector, and the recombinant plasmid was transformed into competent E. coli BL21 for producing recombinant protein. The expressions of SjBAD in different development stages of schistosomula and 42-day male and female worms were determined by real-time PCR. The immunogenicity of the recombinant protein was analyzed by Western blotting and ELISA. The potential of this protein as a vaccine candidate molecule was assessed by testing the worm reduction rate and liver egg reduction rate in the BALB/c mice immunized by the recombinant antigen SjBAD. RESULTS: SjBAD was successfully cloned, the recombinant plasmid pET-28a(+)-SjBAD was successfully expressed in E. coli, and the molecular weight of the recombinant protein was around 22 kDa. Western-blotting showed that the recombinant protein had good immunogenicity. The recombinant protein could induce high level of specific IgG antibodies in the BALB/c mice. SjBAD was expressed in all tested 7-, 14-, 21-, 28-, 35- and 42-day worms, and was highly expressed in 14-day schistosomula, while the expression level in 42-day male worms was higher than that in 42-day female worms. Two in- dependent animal trials showed that 30.82% and 27.87% worm reduction rates, as well as 42.52% and 45.84% liver eggs reduction rates were obtained in the rSjBAD vaccinated group compared with those of the blank control group (both P < 0.05). CONCLUSIONS: The proapoptotic gene SjBAD is successfully cloned and expressed. The gene is expressed in different development stages of S. japonicum. The rSjBAD vaccinated BALB/c mice can obtain a partial protective immunity against S. japonicum infection. PMID- 26263774 TI - [Comparative study of assay methods for in vitro antimalarial drug efficacy testing in Plasmodium falciparum]. AB - OBJECTIVE: To compare four assay methods of in vitro antimalarial drug efficacy testing, including WHO microtest, Plasmodial lactate dehydrogenase (pLDH), Histidine-rich protein II (HRP II) and SYBR Green I, so as to determine a stable, simple, rapid, and economic method for monitoring the drug sensitivity of malaria parasites and screening new antimalarial drugs. METHODS: WHO microtest, pLDH, HRP II and SYBR Green I were applied to test the drug efficacy of chloroquine, piperaquine and amodiaquine against four Plasmodiumfalciparum reference strains (3D7, FCC, K1 and Dd2), respectively. The consistency of the 50% inhibitory concentration (IC50) values from the four assay methods were analyzed by Friedman tests, Partial correlation analysis, Pearson' s correlation analysis and Bland Altman plots. RESULTS: With the initial parasitemia ranged from 0.5% to 1%, there were no statistically significant differences (P> 0.05) among the IC50 values obtained by the four assay methods, which were correlated well (both P< 0.001). WHO microtest was highly labor-intensive, time-consuming and subjective; although HRP II was more sensitive than pLDH and SYBR Green I, which was more expensive; SYBR Green I was a simple, rapid and economic assay method. CONCLUSION: SYBR Green I, as a simple and cost-effective assay method, is suitable for high throughput malaria drug sensitivity monitoring and research of new antimalarial drug screening. PMID- 26263775 TI - [Infection and molecular characteristics of Giardia in clinical diarrheal patients]. AB - OBJECTIVE: To initially understand the infection status and the molecular characteristics of Giardia in clinical diarrheal patients. METHODS: A total of 95 stool samples were collected from the clinical diarrheal patients admitted in a hospital in Shanghai from May to July, 2014, and the Giardia cysts in the samples were examined by an optical microscope. Then the tpi gene of Giardia in the positive samples were amplified by using the nested-PCR method, and the PCR products were sequenced and analyzed by using BLAST, ClustalX 1.83, and the phylogenetic tree was drawn by using MEGA6.0 software. RESULTS: Only one patient was infected with Giardia and the positive detection rate was 1.05%. The Giardia cysts in the fecal specimen were seen clearly under the microscope. Through the identification by PCR, the amplified fragment was about 530 bp, and the sequencing analysis indicated it was Giardia and which was further identified as assemblage B by drawing phylogenetic tree based on tpi gene. Meanwhile, the sequence had 100% homology with the reported sequence from huian (KF271445). CONCLUSIONS: Giardia infection can occur in the clinical diarrheal patients. The study could provide more data for understanding the genetic characteristics of Giardia and the epidemiological study of giardiasis. PMID- 26263776 TI - [Establishment and diagnostic performance of biotin-avidin complex enzyme linked immunosorbent assay of detecting specific IgG4 of clonorchiasis]. AB - OBJECTIVE: To explore the performance of the biotin-avidin complex enzyme linked immunosorbent assay of detecting specific IgG4 for the diagnosis of clonorchiasis. METHODS: The avidin-biotin complex enzyme linked immunosorbent assay of detecting specific IgG4 (IgG4-ABC-ELISA)against Clonorchis sinensis was established, and used to detect the serum samples of patients with clonorchiosis sinensis, schistosomiasis japonica, paragonimiasis, toxoplasmosis, echinococcosis, cysticercosis and sparganosis mansoni. At the same time, these sera were analyzed by the ELISA of detecting IgG4 (IgG4-ELISA) and ELISA of detecting the total IgG (IgG-ELISA) as controls. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and the respective diagnostic performance of the three methods were compared. RESULTS: The IgG4-ABC-ELISA for diagnosis of clonorchiasis was established successfully. The sensitivity and specificity of the IgG4-ABC-ELISA for detecting clonorchiasis were 90.0% and 98.2% respectively, and PPV and NPV were 93.8% and 97.0% respectively. Its diagnostic performance was 96.3%. The sensitivity and specificity of the IgG4-ELISA for detecting clonorchiasis were 86.0% and 98.2% respectively, and PPV and NPV were 93.5% and 95.9% respectively. Its diagnostic performance was 95.4%. The sensitivity and specificity of the IgG-ELISA for detecting clonorchiasis were 94.0% and 88.1% respectively, and PPV and NPV were 70.1% and 98.0% respectively. Its diagnostic performance was 89.4%. The sensitivity of IgG4-ABC-ELISA was higher than that of IgG4-ELISA (P < 0.05), and the specificity of IgG4-ABC-ELISA was higher than that of IgG-ELISA (P < 0.05). CONCLUSIONS: IgG4-ABC-ELISA of detecting specific antibody IgG4 against Clonorchis sinensis has high sensitivity and specificity. Therefore, it has a good application value in the diagnosis of clonorchiasis. PMID- 26263777 TI - [Establishment of animal model for Pneumocystis carinii and study on etiological and molecular biological detection technology]. AB - OBJECTIVE: To establish an animal model for Pneumocystis pneumonia (PCP) and to study the etiological and molecular biological technology for PCP detection. METHODS: SD and Wistar rats were divided into experimental and control groups randomly. The animals in the experimental group were immunosuppressed by subcutaneous injection with dexamethasone 2 mg per time per rat, twice a week, while those in the control group underwent the same way of injection with physiological saline simultaneously. After the induction for 8 weeks, all the rats were killed and their bronchoalveolar lavage fluid (BALF) and lung tissues were collected for smear making and microscopic detection. Meanwhile, the BALF samples were detected by PCR, and the products were sequenced and compared with rat source PCP in GenBank. RESULTS: A total of 34 samples of lung tissue and BALF were observed. The etiological detection showed that the infection rates of the rats in the experimental and control groups were 29.2% (7/24) and 0, respectively. In the experimental group, the infection rates of SD and Wistar rats were 25.0% (3/12) and 33.3% (4/12), respectively, and the difference between them was not statistically significant (P = 0.31). The positive detection rates of the lung smears and BALF from SD rats in the experimental group were 25.0% (3/12) and 16.7% (2/12), respectively, while those in Wistar rats in the experimental group were 33.3% (4/12) and 16.7% (2/12), respectively, and there were no statistically significant difference between them (P = 0.34, 0.24). A total of 28 samples of BALF were detected by PCR, and the positive detection rates of rats in the experimental group and control group were 91.7% (26/28) and 0, respectively. The sequence analysis of the PCR products showed that it shared 100% homology with the genes of rat source PCP in Gen Bank (JX499145, GU133622 and EF646865). CONCLUSIONS: The animal model of PCP can be established by subcutaneous injection with dexamethasone. As animal models, there are no significant difference between SD rats and Wistar rats. PCR method is suitable for PCP detection at the early stage of infection, while etiological detection with high missing rate is not a right option. PMID- 26263778 TI - [In vitro killing of Trichinella spiralis muscle larvae by exogenous nitric oxide from SNP]. AB - OBJECTIVE: To study the lethal effect of exogenous nitric oxide donor sodium nitroprusside (SNP) on the muscle larvae of Trichinella spiralis in vitro cultivation. METHODS: T. spiralis muscle larvae isolated from the infected BALB/c mice were formulated into a 1,000 larva/ml suspension with RPMI 1640 medium, and 0.1 ml suspension per orifice was cultured with SNP at 37 degrees C in a humidified 5% CO2 atmosphere. The final concentrations of SNP were 0.02, 0.05, 0.10, 0.20, 0.50 and 1.00 mmol/L, respectively, and then the experiments were divided into 5 groups:1.00 mmol/L SNP (control group, Group A), 0.15 mmol/L FeSO4+ 1.00 mmol/L SNP (Group B), 1.00 mmol/L L-cysteine + 1.00 mmol/L SNP (Group C), 0.15 mmol/L FeSO4+ 1.00 mmol/L L-cysteine + 1.00 mmol/L SNP (Group D) and 0.15 mmol/L Hemoglobin + 1.00 mmol/L SNP (Group E). All the groups were incubated with T. spiralis muscle larvae in RPMI 1640 medium. The survivability of the muscle larvae was observed by steromicroscope and the differences of inhibition ratio among these groups were analyzed 4 d after the incubation. Results SNP 0.02 mmol/L was not cytotoxic to the muscle larvae with an inhibition of (5.50 +/- 1.80) %. The mortality rates of SNP 0.05, 0.10, 0.20, 0.50, 1.00 mmol/L groups were (20.19+/-2.71)%, (29.21+/-2.12)%, (41.81+/-2.03)%, (47.85+/-3.79)%, (60.98+/ 5.19)%, respectively, significantly higher than that of the control group[(4.93+/ 0.25) %, all P < 0.051]. There was a positive liner correlation between the mortality of muscle larvae and SNP concentrations in the range of 0.02-1.00 mmol/L. Next, Group A, B, C, D and E led to the mortalities from (60.98+/-5.19)% to (49.48+/-1.34)%, (47.29+/-2.79)%, (26.28+/-1.37)%, (17.93+/-3.49)%, respectively, and all the differences between Group A and the other four groups were statistically significant (all P < 0.05). CONCLUSIONS: Exogenous nitric oxide released from SNP can kill the muscle larvae of T. spiralis. However, hemoglobin, L-cysteine, and FeSO4 can reverse the lethal effect on the parasites. The best inhibitor was hemoglobin. PMID- 26263779 TI - [Cloning, expression, purification and identification of Toxoplasma gondii SAG2 gene in Escherichia coli]. AB - OBJECTIVE: To construct a recombinant plasmid containing surface antigen 2(SAG2) gene of Toxoplasma gondii and express it in Escherichia coli. METHODS: The truncated SAG2 gene was amplified from the genomic DNA of T. gondii RH strain and cloned into plasmid pGEX-4T. Then the recombinant pGEX-4T-SAG2 was induced by IPTG and expressed in E. richia col BL21. The expressed proteins were analyzed by SDS-PAGE and purified, and the immunogenicity of the product was analyzed by Western blotting. RESULTS: The amplified SAG2 gene was about 561 bp, which was accorded to the expectation. The recombinant plasmid was constructed successfully by digested with double restriction enzyme and confirmed with DNA sequencing. SDS PAGE and Western blotting showed the molecular weight of SAG2 fusion protein was about 47 ku, and the protein could be identified by GST-tag antibody. CONCLUSION: The truncated SAG2 gene of T. gondii has been successfully cloned and expressed in E. coli BL21 cells, and the recombinant protein has immunogenicity. PMID- 26263780 TI - [Monitoring of sentinel mice and risk assessment of schistosomiasis transmission in key regions of Yunnan Province in 2014]. AB - OBJECTIVE: To establish and perfect the surveillance and forecast system of schistosomiasis, and timely discover the suspicious high risk environments for preventing the human and livestock from schistosomiasis. METHODS: Eight villages of three counties were selected as survey points. Then, the surveillance and forecast of sentinel mice were carried out in the key water regions. The recovered sentinel mice were dissected in laboratory. The sentinel mouse serum antibodies against schistosome were detected by ELISA, the suspicious water contacts of residents and livestock were investigated and the results were analyzed, and the epidemic risk was assessed. RESULTS: Totally 300 sentinel mice were placed, the recovery rate was 94.67%, and the mortality rate was 8.80%. There were no mice with positive serum antibodies against schistosome, and the results of the dissection of all the sentinel mice were negative. The humans who contacted with the suspicious water were mainly villagers, students, children and fishermen by washing hands and feet, washing vegetables, harvesting, fishing and swimming. The Oncomelania hupensis snail areas, human infection rates, and cattle infection rates were obviously declined in recent 3 years. However, the epidemic risks still existed. CONCLUSION: Although schistosomiasis transmission was effectively controlled in the three counties, the comprehensive control measures still should be strengthened. PMID- 26263781 TI - [Risk factors of portal vein thrombosis after surgery for advanced schistosomiasis portal hypertension]. AB - OBJECTIVE: To explore the risk factors of portal vein thrombosis (PVT) after splenectomy and esophagogastric devascularization for advanced schistosomiasis portal hypertension. METHODS: The clinical data were collected retrospectively from 211 advanced schistosomiasis portal hypertension patients after splenectomy and esophagogastric devascularization from August, 2004 to March 2014, and all the data were analyzed statistically for the risk factors of PVT after the surgery by single factor analysis and Logistic regression analysis. RESULTS: Totally 59 patients were found with PVT and the incidence was 27.96% (59/211). The single factor analysis showed that 8 factors were related to PVT after surgery, including the history of upper gastrointestinal hemorrhage, the diameter of portal vein, the diameter of splenic vein, esophageal varices, ascites, portal hypertension gastropathy, gastric varices , and blood ammonia level. The Logistic regression analysis showed that the independent risk factors of PVT were broadening of the diameter of portal vein (OR = 1.763 , P = 0.000) and portal hypertension gastropathy (OR = 1.089, P = 0.037). CONCLUSIONS: The incidence of PVT after surgery for advanced schistosomiasis is high, and the independent risk factors are broadening of diameter of portal vein and portal hypertension gastropathy. PMID- 26263782 TI - [Survey of current situation of schistosomiasis health education in Wuxi City]. AB - OBJECTIVE: To understand the current situation of schistosomiasis health education in in Wuxi City where schistosomiasis transmission has been interrupted, so as to provide the evidence for formulating the health education strategies. METHODS: Face to face interviews and a professional designed questionnaire were used to collect the information of the current schistosomiasis health education and investigate the awareness of schistosomiasis knowledge in primary and middle schools and in communities. RESULTS: The total awareness rate of schistosomiasis knowledge was 87.7% among 873 students and the figure was 83.0% among 693 community residents. The students who studied in the schools with more than 1 class hour of schistosomiasis health education, completed schistosomiasis health education material or teaching plan, and implementing health education through multiple ways had higher knowledge awareness rates compared with the schools without (chi2 = 291.408, 709.622, 13.751, all P <0.001). The residents living in the communities with schistosomiasis health education through broadcast/TV or square propaganda had a higher knowledge awareness rate compared with the communities without (chi2= 90.772, 47.436, all P < 0.001). CONCLUSION: The awareness rates of schistosomiasis knowledge among both students and community residents in Wuxi City are low. Therefore, the schistosomiasis control health education should be strengthened. PMID- 26263783 TI - [Investigation of intestinal nematode infections in Hongze County, Jiangsu Province]. AB - OBJECTIVE: To understand the situation of intestinal nematode infections and assess the preventive effects, so as to provide the evidence for formulating the further measures of prevention. METHODS: Five villages from 5 townships of different geographical locations were selected and 500 residents of each village were surveyed. The eggs of intestinal nematodes were detected by the Kato-Katz technique, and 50 students and 50 residents per village were investigated by questionnaires about health education. RESULTS: Among 3 011 people detected, 17 persons were infected with intestinal nematodes and the total infection rate was 0.56%. The rates of Ascaris lumbricoides, hookworm, Trichuris trichiura, Enterobius vermicularis, and Trichostrongylus were 0.10%, 0.33%, 0.03%, 0.03% and 0.07%, respectively. The awareness rate of health knowledge was 97.80% and the formation rate of health behavior was 97.00%. CONCLUSION: The infection rates of intestinal nematodes, the awareness rate of health knowledge and the formation rate of health behavior in the population of Hongze County have achieved the criteria of effective control of intestinal parasitic diseases. PMID- 26263784 TI - [Epidemiological analysis of malaria prevalence in Hubei Province in 2013]. AB - OBJECTIVE: To explore the endemic situation of malaria in Hubei Province in 2013, so as to put forward effective elimination strategies and measures. METHODS: The data of malaria cases were searched from the Disease Reporting Information System of Chinese Center for Disease Control and Prevention and analyzed with the descriptive epidemiological method for the epidemiological characteristics of malaria in Hubei Province in 2013. RESULTS: A total of 129 malaria cases were reported in Hubei Province in 2013 with the incidence of 0.02/10,000, and all of them were imported cases, in which 86 cases with Plasmodium falciparum infection, 32 cases with P. vivax infection, 7 cases with P. ovale infection and 4 cases with P. malariae infection. The distribution of malaria cases was concentrated in Wuhan City (76 cases), Yichang City (10 cases), Xiangyang City (7 cases) and Huangshi City (6 cases), accounting for 76.74% of the total cases. There was no significant seasonal variation in the reporting time of the cases. Totally 99.22% of the cases were male, the age distribution concentrated mainly on 20-49 years. The occupation distribution concentrated mainly on the worker, farmer, cadre staff and migrant worker. The main original areas of the imported cases were Africa (111 cases, 86.05%) and Asia (17 cases, 13.18%). CONCLUSIONS: There is no local malaria cases reported in Hubei Province in 2013, however, the imported malaria cases are increased. Therefore, it is necessary to further strengthen the multi-sector collaboration of vector control, while the health education should be intensified especially in the key population. PMID- 26263785 TI - [Epidemic situation of malaria in Taixing City, 2005-2013]. AB - OBJECTIVE: To analyze the malaria situation and control measures in recent years in Taixing City, so as to provide the evidence for formulating the reasonable countermeasures in the future. METHODS: The information of malaria prevalence, the reported data of blood examinations for fever persons and the epidemiological data were collected and the malaria incidence, population distribution, and the imported cases were analyzed. RESULTS: A total of 37 malaria cases were reported from 2005 to 2013 and the incidences were from 0.0078/10,000 to 0.0669/10,000 with the large ascensional range. There were 34 imported malaria patients (91.89% of the total malaria cases) including 2 patients infected outside Taixing City, 2 outside Jiangsu Province, and 30 outside China. Among the 30 patients overseas infected, there was 1 vivax malaria case, there were 2 ovale malaria cases, and 27 falciparum malaria cases. There were incidences throughout the year and no obvious seasonal characteristics. The cases were mainly distributed from 30 to 49 years old (83.78%). CONCLUSIONS: The malaria cases in Taixing City are mainly overseas imported, and the incidence presents a rising trend. Therefore, the relevant authority should enhance the malaria supervision and management, especially for floating population. PMID- 26263786 TI - [Research of preferences and security management of tourists in Poyang Lake based on schistosomiasis prevention]. AB - OBJECTIVE: To discuss the prevention of schistosomiasis in tourism of lake region. METHODS: The seasonal distribution of tourism activities and spatial distribution of scenic spots, as well as the coupling between space and temporal of Oncomelania snail distribution and the transmission time of schistosomiasis in Poyang Lake region were analyzed. The travel preference of schistosomiasis susceptible population was surveyed by questionnaires and interviews. RESULTS: There were couplings of space and temporal between tourism activities in Poyang Lake region and transmission time of schistosomiasis as well as space distribution of snails, respectively. The most popular tourism items were Shuishangrenjia (overwater household) and fishing folk culture with property of participation and experience. CONCLUSION: The suggestion is to establish health records of tourists, carry out health education of schistosomiasis, and enhance the management of tourism and activities of tourists. PMID- 26263787 TI - [Application effect of Oncomelania hupensis snail crushers in batch detection]. AB - OBJECTIVE: To evaluate the application effect of Oncomelania hupensis snail crusher in batch detection. METHODS: The O. hupensis snail crushers and triangular flasks for cercariae shedding were made. The uninfected snails were divided into 4 groups with the snail number of 50, 100, 200, 300, respectively, and then they were put in 40 triangular flasks, 10 flasks each group. Three flasks in each group were randomly selected, and 12 schistosome infected O. hupensis snails were put into the flasks (1 snail per flask). The 12 flasks with infected O. hupensis snails were put back to each group and were numbered uniformly. The O. hupensis snails in each group were crushed by the O. hupensis snail crushers, and the crushing rate of snails, and average crushing time and duration were recorded. When all the O. hupensis snails were crushed, water was added into the flasks, and water films from each flask were taken and observed under microscopes, the number of cercariae was recorded and the detection rates of each group were calculated. Meanwhile, the O. hupensis snails in the field were collected and detected by the crushing method and crushing and shedding method with O. hupensis snail crushers, and the coincidence rate of the two methods was calculated. RESULTS: The crushing rate of snails in all the 4 groups were 100% , the average crushing times of groups with 50, 100, 200, 300 snails were 15.70, 23.20, 32.20, 39.20, respectively, and the average duration was 1.01, 1.70, 2.00, 3.00 min, respectively. Both the crushing time and duration were positively correlated with the number of snails detected (r = 0.68, 0.73, both P <0.01). The detection rates of cercariae in all the 4 groups were 100%. In the field application, 109 snails were detected by the crushing method, 620 ones were detected by the crushing and shedding method with O. hupensis snail crushers, and no infected snails were found, the coincidence rate of the two methods were 100%. CONCLUSION: The O. hupensis snail crusher with the advances of easy operation and labor-saving is valuable of field promotion. PMID- 26263788 TI - [Analysis of cost-effectiveness of molluscacide combined with herbicide by spraying]. AB - OBJECTIVE: To explore an economical and efficient molluscicidal method suitable for large area of nursery stock field. METHODS: Two nursery stock fields with Oncomelania hupensis were selected as experimental sites, and an experimental group and a control group were set. In the experimental group, the molluscacide and herbicide were alternately used (a purification molluscicidal method) during the period of May to October, 2011. In the control group, grass shoveling and soil burying combined with molluscacide were used in the same period. The snail control effects of the two groups were observed and the costs of the two methods were analyzed. RESULTS: No living snails were found in both experimental and control groups three consecutive years after the snail control intervention above mentioned. The costs of snail control intervention in the experimental group and control group were 0.90 and 1.80 Yuan/m2, respectively. CONCLUSION: The effect of the purification molluscicidal method in nursery stock field is satisfying, and the cost is lower. PMID- 26263789 TI - [Effect of "one village, one control strategy" on schistosomiasis control in Qianjiang City]. AB - OBJECTIVE: To evaluate the effect of "one village, one control strategy" on schistosomiasis control in Qianjiang City. METHODS: The villages with human and/or bovine schistosome infection rate being more than 1.5% in 2011 were chosen as the trial villages. According to the epidemic characteristics of schistosomiasis and control difficulties of the villages, the "one village, one control strategy" was performed and the control effects were evaluated. RESULTS: By the end of 2013, the infection rates of human and bovine in the trial villages decreased by 45.91% (chi2 = 469.19, P < 0.01) and 49.38% (chi2 = 11.46, P < 0.01), respectively, and all the infection rates of human and bovine in those villages were less than 1%. CONCLUSION: The "one village, one control strategy" is effective for schistosomiasis control, which can rapidly reduce the prevalence of schistosomiasis. PMID- 26263790 TI - [Clinical effect of cardiac peripheral vascular disconnection in emergency treatment of gastroesophageal bleeding caused by portal hypertension]. AB - OBJECTIVE: To evaluate the clinical effect of cardiac peripheral vascular disconnection in the emergency treatment of gastroesophageal bleeding caused by portal hypertension. METHODS: The data of 43 cases of cardiac peripheral vascular disconnection in the emergency treatment of gastroesophageal bleeding caused by portal hypertension were collected and analyzed retrospectively from 2001 to 2012. RESULTS: The bleeding in all the 43 patients who received the cardiac peripheral vascular disconnection was stopped. Totally 42 patients were recovered (97.67%), but 1 died from hepatic failure (2.38%). CONCLUSION: The clinical effect of cardiac peripheral vascular disconnection in the emergency treatment of gastroesophageal bleeding caused by portal hypertension is definite, and the operation is also simple. PMID- 26263791 TI - [Evaluation on effect of treatment and assistance to advanced schistosomiasis patients in Qianjiang City]. AB - OBJECTIVE: To evaluate the implementation and effect of the program of treatment and assistance to advanced schistosomiasis patients in Qianjiang City. METHODS: The data about the program from 2004 to 2012 were collected and analyzed, and the analysis of cost-effectiveness was performed. Meanwhile, 160 patients were sampled and surveyed about the recovery of their health. RESULTS: From 2004 to 2012, totally 2 363 person-times' patients received the treatment, and 339 patients were cured clinically. On average, each patient received 3.11 times of treatment and 22.28 d of hospitalization, the treatment cost was 5,382.87 yuan per year for each patient, and the cost-effectiveness was 12.7 thousand yuan per life-year-saved. CONCLUSION: The program of treatment and assistance to advanced schistosomiasis patients cures a part of patients and improves the working capacity and life quality of the patients. PMID- 26263792 TI - [Qualitative research on psychological experiences of advanced schistosomiasis patients]. AB - OBJECTIVE: To understand the psychological experiences of advanced schistosomiasis patients, so as to provide the evidence for formulating a systematic and scientific nursing scheme. METHODS: Twenty advanced schistosomiasis patients were studied with the qualitative research method. RESULTS: There were 70% (14/20) patients with labor limited, 50% (10/20) with a moderate anxiety, irritability and other negative emotions, and 65% (13/20) with moderate discomfort. CONCLUSIONS: Most of advanced schistosomiasis patients have negative emotions. Therefore, the suitable psychological nursing should be given to these patients to improve their quality of life. PMID- 26263793 TI - [Epidemiological analysis of malaria in Wenzhou City in 2013]. AB - OBJECTIVE: To understand the characteristics of malaria prevalence in Wenzhou City in 2013, so as to provide the evidence for improving the elimination program of malaria. METHODS: The epidemiological data of malaria in Wenzhou City in 2013 were collected from the Chinese information system for disease control and prevention, and analyzed with the descriptive epidemiological methods for epidemiological characteristics of malaria. RESULTS: Totally 34 imported malaria cases were reported in Wenzhou City in 2013 with the incidence of 0.37 per 100,000 people. Plasmodiumfalciparum, P. ovale and P. vivax were identified in 31, 1 and 2 cases, respectively. No death cases were reported, and 64.71% (22/34) of the cases were reported in Cangnan County, Lucheng District and Rui' an City. The malaria cases were mostly concentrated in persons aged 20-49 years with male to female sex ratio at 4.67: 1, and the predominant portion of cases were workers and commercial service personnel. Totally 97.06% of the cases were imported from Africa. CONCLUSIONS: The malaria endemic situation is relatively stable and no local malaria cases are reported in Wenzhou City in 2013. In order to achieve the goal of malaria elimination, the management and education of the transient population should be strengthened. PMID- 26263794 TI - [Surveillance of endemic situation of schistosomiasis in a national surveillance site in Honghu City from 2005 to 2013]. AB - OBJECTIVE: To understand the dynamics of schistosomiasis japonica in a national surveillance site in Honghu City, Hubei Province, China, so as to provide the evidence for formulating the intervention strategy of schistosomiasis control in the whole city. METHODS: The surveillance was performed in the surveillance village according to The National Surveillance Scheme of Schistosomiasis Japonica, and the results were analyzed statistically from 2005 to 2013. RESULTS: The schistosome infection rates in residents and cattle decreased from 1.76% and 20.93% in 2005 to 0 in 2013, respectively. The density of living Oncomelania snails decreased from 4.20/0.1m2 to 0.17/0.1m2, respectively. No infected snails were found during the period of 9 years in succession. The total area of snail control with molluscicidal drugs was 68.38 hm2 in the monitoring sites during the period of 9 years, and the expanded chemotherapy was performed for 634 person times. Sixteen (person-time) advanced schistosomiasis patients received the treatment and salvation. The health education was carried out in 3 836 (person times) students. Totally 5 685 leaflets of health education were distributed, and 17 bulletin boards of health education were performed. Five warning boards were set up at the environments with snails. CONCLUSIONS: The transmission of schistosomiasis in the surveillance site in Honghu City shows a gradually decreasing trend year by year. However, the surveillance and control of snails still should be strengthened. PMID- 26263795 TI - [Pathology and pathogenesis of liver fibrosis induced by Schistosoma japonicum]. AB - Schistosomiasis is a widely distributed parasitic zoonoses that threatens human' s health and social economic development. China is one of the most endemic countries in the world. Schistosoma egg are mainly lodged in the liver and intestinal tissues. There, the eggs induce a granulomatous host immune response largely characterized by lymphocytes, eosinophils, and alternatively activated macrophages. The process of granuloma formation induces chronic inflammation that leads to liver fibrosis accompanied by obvious manifestations such as hepatosplenomegaly and ascites. In this article, we review the advanced progress in research about schistosomiasis hepatic fibrosis, including the pathology of liver fibrosis, the formation and modulation of granuloma and fibrosis, the key inflammatory factors and related signaling pathways, the regulatory role of ncRNA in the process of fibrosis, and anti-fibrosis treatment and new drugs development. PMID- 26263796 TI - [Advances in research of Toxoplasma gondii rhoptry protein ROP16]. AB - ROP16 is one member of the rhoptrys protein family in Toxoplasma gondii. In its protein structure, there exists serine/threonine kinase domain, which is the important virulence factor in the invasion process of T. gondii. ROP16 can secretes into the nucleus of the host cells, and can phosphorylate the signal transducer and activator of transcription (STAT3/6) and interfere the signal transduction pathway in the host cell. In this paper, the structure and function, as well as the immunogenicity of ROP16 are summarized. PMID- 26263797 TI - Effects of a 1:1 inspiratory to expiratory ratio on respiratory mechanics and oxygenation during one-lung ventilation in patients with low diffusion capacity of lung for carbon monoxide: a crossover study. AB - STUDY OBJECTIVE: To investigate the effects of a 1:1 inspiratory-to-expiratory (I:E) ventilation ratio on oxygenation and respiratory mechanics during one-lung ventilation (OLV) in patients with low diffusion capacity of lung for carbon monoxide (DLCO). DESIGN: Prospective, randomized, crossover study. SETTING: Operating room, university hospital. PATIENTS: Twenty-six patients with a preoperative DLCO less than 80% who were scheduled for lung lobectomy requiring OLV under general anesthesia. INTERVENTIONS: In the first group (n = 13), OLV was begun with a 1:1 I:E ratio, which was switched to a 1:2 I:E ratio after 30 minutes. In the second group (n = 13), the modes of ventilation were performed in the opposite order. Pressure-controlled ventilation with 5 cm H2O of positive end expiratory pressure and a tidal volume of 5 to 8 mL/kg was applied during OLV. MEASUREMENTS: Arterial and central venous blood gas analyses were recorded and used to calculate intrapulmonary shunt fraction and physiologic dead space. These measurements were taken at 4 time points: 10 minutes after two-lung ventilation in the lateral decubitus position, 30 minutes after initiation of OLV, 30 minutes after switching the I:E ratio, and 10 minutes after two-lung ventilation was resumed. MAIN RESULTS: There was no difference in arterial oxygen tension during OLV between the 2 groups (P = .429). Arterial carbon dioxide tension and peak airway pressure were lower in the 1:1 group than in the 1:2 group (P = .003; P = .008). Physiologic dead space was also decreased in the 1:1 I:E ratio group (P = .003). Mean airway pressure and dynamic compliance were higher in the 1:1 group (P = .003; P = .007). CONCLUSIONS: Pressure-controlled ventilation with a 1:1 I:E ventilation ratio did not improve oxygenation in patients with low DLCO during OLV compared with a 1:2 I:E ventilation ratio. However, it did provide benefits in terms of respiratory mechanics and increased the efficiency of alveolar ventilation during OLV. PMID- 26263798 TI - What to publish. PMID- 26263799 TI - Systematic review of enhanced recovery after gastro-oesophageal cancer surgery. AB - INTRODUCTION: Fast track methodology or enhanced recovery schemes have gained increasing popularity in perioperative care. While evidence is strong for colorectal surgery, its importance in gastric and oesophageal surgery has yet to be established. This article reviews the evidence of enhanced recovery schemes on outcome for this type of surgery. METHODS: A systematic literature search was conducted up to March 2014. Studies were retrieved and analysed using predetermined criteria. RESULTS: From 34 articles reviewed, 18 eligible studies were identified: 7 on gastric and 11 on oesophageal resection. Three randomised controlled trials, five case-controlled studies and ten case series were identified. The reported protocols included changes to each stage of the patient journey from pre to postoperative care. The specific focus following oesophageal resections was on early mobilisation, a reduction in intensive care unit stay, early drain removal and early (or no) contrast swallow studies. Following gastric resections, the emphasis was on reducing epidural anaesthesia along with re establishing oral intake in the first three postoperative days and early removal of nasogastric tubes. In the papers reviewed, mortality rates following fast track surgery were 0.8% (9/1,075) for oesophageal resection and 0% (0/329) for gastric resection. The reported morbidity rate was 16.5% (54/329) following gastric resection and 38.6% (396/1,075) following oesophageal resection. Length of stay was reduced in both groups compared with conventional recovery groups in comparative studies. CONCLUSIONS: The evidence for enhanced recovery schemes following gastric and oesophageal resection is weak, with only three (low volume) published randomised controlled trials. However, the enhanced recovery approach appears safe and may be associated with a reduction in length of stay. PMID- 26263800 TI - When might an operative complication be regarded as acceptable? Part 2: Judicial factors that influence the finding of fault during surgical litigation. AB - In cases where surgeons face litigation over operative misadventure, the result of a trial is uncertain. In order to identify factors in cases of surgical litigation that have influenced the final decision of the courts, we have previously reviewed reported cases where the outcome turned on actions taken by surgeons. We now turn our attention to judicial attitudes to evidence that play a role in the determination of the case. PMID- 26263801 TI - Conservative management of aortic arch injury following penetrating trauma. AB - Aortic arch injuries following penetrating trauma are typically lethal events with high mortality rates. Traditionally, the standard of care for patients presenting with penetrating injury and aortic involvement has included surgical intervention. We report the case of a 31-year-old man who was managed non operatively after sustaining multiple stab wounds to the left chest and presenting with mid aortic arch injury. PMID- 26263802 TI - Durability of giant hiatus hernia repair in 455 patients over 20 years. AB - INTRODUCTION: The surgical management of symptomatic giant hiatus hernia (GHH) aims to improve quality of life (QoL) and reduce the risk of life threatening complications. Previous reports are predominantly those with small sample sizes and short follow-up periods. The present study sought to assess a large cohort of patients for recurrence and QoL over a longer time period. METHODS: This was a follow-up study of a prospectively collected database of 455 consecutive patients. Primary repair of GHH was evaluated by endoscopy/barium meal for recurrence and a standardised symptom questionnaire for QoL. Recurrence was assessed for size, elapsed time, oesophagitis and symptoms. RESULTS: Objective and subjective review was achieved in 91.9% and 68.6% of patients. The median age was 69 years (range: 15-93 years) and 64% were female. Laparoscopic repair was completed in 95% (mesh in 6% and Collis gastroplasty in 7%). The 30-day mortality rate was 0.9%. The proportion of patients alive at five and ten years were 90% and 75% respectively. Postoperative QoL scores improved from a mean of 95 to 111 (p<0.01) and were stable over time (112 at 10 years). The overall recurrence rate was 35.6% (149/418) at 42 months; this was 11.5% (48/418) for hernias >2cm and 24.2% (101/418) for <2cm. The rate of new recurrence at 0-1 years was 13.7% (>2cm = 3.4%, <2cm = 10.3%), at 1-5 years it was 30.8% (>2cm = 9.5%, <2cm = 21.3%), at 5-10 years it was 40.1% (>2cm = 13.8%, <2cm = 26.3%) and at over 10 years it was 50.0% (>2cm = 25.0%, <2cm = 25.0%). Recurrence was associated with oesophagitis but not decreased QoL. Revision surgery was required in 4.8% of cases (14.8% with recurrence). There were no interval major GHH complications. CONCLUSIONS: Surgery has provided sustained QoL improvements irrespective of recurrence. Recurrence occurred progressively over ten years and may predispose to oesophagitis. PMID- 26263803 TI - Renal injury management in an urban trauma centre and implications for urological training. AB - INTRODUCTION: The aim of this study was to analyse the treatment and management of renal injury patients presenting to our major trauma unit to determine the likelihood of patients needing immediate nephrectomy. METHODS: The Trauma Audit and Research Network (TARN) database was used to review trauma cases presenting to our department between February 2009 and September 2013. Demographic data, mechanism and severity of injury, grade of renal trauma, management and 30-day outcome were determined from TARN data, electronic patient records and imaging. RESULTS: There were a total of 1,856 trauma cases, of which 36 patients (1.9%) had a renal injury. In this group, the median age was 28 years (range: 16-92 years), with 28 patients (78%) having blunt renal trauma and 8 (22%) penetrating renal trauma. The most common cause for blunt renal trauma was road traffic accidents. Renal trauma cases were stratified into American Association for the Surgery of Trauma (AAST) grades (grade I: 19%, grade II: 22%, grade III: 28%, grade IV: 28%, grade V: 0%). All patients with grade I and II injuries were treated conservatively. There were three patients (1 with grade III and 2 with grade IV renal injuries) who underwent radiological embolisation. One of these patients went on to have a delayed nephrectomy owing to unsuccessful embolisation. CONCLUSIONS: Trauma patients rarely require emergency nephrectomy. Radiological selective embolisation provides a good interventional option in cases of active bleeding from renal injury in haemodynamically stable patients. This has implications for trauma care and how surgical cover is provided for the rare event of nephrectomy. PMID- 26263804 TI - Accuracy of a multidisciplinary team-led discussion in predicting postmastectomy radiotherapy. AB - INTRODUCTION: Immediate breast reconstruction (IBR) is performed increasingly following mastectomy for breast cancer. The literature suggests higher reconstructive failure and poorer cosmesis in the subgroup of patients receiving postmastectomy radiotherapy (PMRT) following IBR. We set out to determine the accuracy of a multidisciplinary team (MDT) discussion in predicting PMRT. METHODS: Preoperative MDT discussions were recorded prospectively over a 12-month period (from February 2011) in a symptomatic breast unit. The estimated need for PMRT was stratified into 'PMRT not required', 'PMRT possibly required', 'PMRT probably required' and 'PMRT required' groups. RESULTS: Of 156 referrals included in the study, 76 patients (49%) underwent mastectomy: 61 simple mastectomy, 10 skin sparing mastectomy (SSM) and delayed-immediate breast reconstruction, 3 SSM and implant-based IBR, and 2 mastectomy IBR with an autologous flap. The IBR rate was therefore 19.7%. The proportion of patients who received PMRT was 14% (3/21) in the 'PMRT not required', 30% (7/23) in the 'PMRT possibly required', 65% (9/14) in the 'PMRT probably required' and 94% (17/18) in the 'PMRT required' groups. Assigning a linear numerical score (1-4) to these groups (higher score representing greater likelihood of receiving PMRT), the predicted need for PMRT correlated with the proportion of patients who ultimately received PMRT (linear regression r(2)=0.98, p=0.01). CONCLUSIONS: This study has examined the factors influencing MDT discussions regarding IBR, demonstrating that the MDT is reasonably accurate at predicting need for PMRT. Whether such accuracy is clinically adequate and/or reproducible across units is debatable. PMID- 26263805 TI - Single incision glove port laparoscopic colorectal cancer resection. AB - INTRODUCTION: The advantages of single port surgery remain controversial. This study was designed to evaluate the safety and feasibility of single incision glove port colon resections using a diathermy hook, reusable ports and standard laparoscopic straight instrumentation. METHODS: Between June 2012 and February 2014, 70 consecutive patients (30 women) underwent a colonic resection using a wound retractor and glove port. Forty patients underwent a right hemicolectomy through the umbilicus and thirty underwent attempted single port resection via an incision in the right rectus sheath (14 high anterior resection, 13 low anterior resection, 3 abdominoperineal resection). RESULTS: Sixty-two procedures (89%) were completed without conversion to open or multiport techniques. Four procedures had to be converted and additional ports were needed in four other patients. The postoperative mortality rate was 0%. Complications occurred in six patients (9%). Two cases were R1 while the remainder were R0 with a median nodal harvest of 20 (range: 9-48). The median length of hospital stay was 5 days (range: 3-25 days) (right hemicolectomy: 5 days (range: 3-12 days), left sided resection: 6 days (range: 4-25 days). At a median follow-up of 14 months, no port site hernias were observed. CONCLUSIONS: Single incision glove port surgery is an appropriate technique for different colorectal cancer resections and has the advantage of being less expensive than surgery with commercial single incision ports. PMID- 26263806 TI - Validation of a grading system for complicated diverticulitis in the prediction of need for operative or percutaneous intervention. AB - INTRODUCTION: The current surgical management of acute complicated diverticulitis has seen a major paradigm shift from routine operative intervention to a more conservative approach. This has been made possible by the widespread availability of computed tomography (CT) to enable stratification of the disease severity of acute complicated diverticulitis. The aim of this study was to retrospectively validate a CT grading system for acute complicated diverticulitis in the prediction of the need for operative or percutaneous intervention. METHODS: Hospital and radiology records were reviewed to identify patients with acute complicated diverticulitis confirmed by CT. A consultant gastrointestinal radiologist, blinded to the clinical outcomes of patients, assigned a score according to the CT grading system. RESULTS: Three hundred and sixty-seven patients (34.6%) had CT performed for acute diverticulitis during the study period. Forty-four patients (12.0%) had acute complicated diverticulitis (abscess and/or free intraperitoneal air) confirmed on CT. There were 22 women (50%) and the overall median age was 59 years (range: 19-92 years). According to the CT findings, there was one case with grade 1, eighteen patients with grade 2, four with grade 3 and twenty-one with grade 4 diverticulitis. Three patients with grade 2, three patients with grade 3 and ten patients with grade 4 disease underwent acute radiological or surgical intervention. CONCLUSIONS: The use of a CT grading system for acute complicated diverticulitis did not predict the need for acute radiological or operative intervention in this small study. Decision making guided by the patient's clinical condition still retains a primary role in the management of acute complicated diverticulitis. PMID- 26263807 TI - The efficacy of adjuvant imatinib therapy in improving the prognosis of patients with colorectal gastrointestinal stromal tumours. AB - INTRODUCTION: Although it has now been accepted that imatinib is a valid treatment for gastrointestinal stromal tumour (GIST) patients in the adjuvant setting, information on its clinical efficacy in improving the prognosis for patients with colorectal GISTs is limited. METHODS: The clinical and follow-up records of 42 colorectal GIST patients who underwent surgical resection at our institution between January 2004 and December 2013 were reviewed retrospectively. The effect of postoperative imatinib treatment on recurrence free survival and overall survival time was analysed with the Kaplan-Meier method and the multivariate Cox proportional hazards model. RESULTS: Sixteen patients were assigned to imatinib treatment (imatinib group) after surgical tumour resection while twenty-six patients did not receive any adjuvant treatment (control group). The one, three and five-year recurrence free survival rates were 100%, 90% and 77% respectively. This was significantly higher than in the control group (92%, 53% and 36%) (logrank test, p=0.012). The one, three and five-year overall survival rates were 100%, 91% and 68% in the imatinib group compared with 96%, 77% and 39% in the control group (logrank test, p=0.021). Analysis with the multivariate Cox regression model yielded similar results on the efficacy of adjuvant imatinib in prolonging both recurrence free survival (hazard ratio [HR]: 0.23, 95% confidence interval [CI]: 0.07-0.80) and overall survival (HR: 0.20, 95% CI: 0.05-0.91). CONCLUSIONS: Adjuvant imatinib therapy seems to be effective in decreasing the risk of tumour occurrence and prolonging the overall survival time in colorectal GIST patients. PMID- 26263808 TI - Does arthroscopic subacromial decompression improve quality of life. AB - INTRODUCTION: There has been a significant rise in the volume of subacromial decompression surgery performed in the UK. This study aimed to determine whether arthroscopic subacromial decompression improves health related quality of life in a cost effective manner. METHODS: Patients undergoing arthroscopic subacromial decompression surgery for impingement were enrolled between 2012 and 2014. The Oxford shoulder score and the EQ-5DTM instruments were completed prior to and following surgery. A cost-utility analysis was performed. RESULTS: Eighty-three patients were eligible for the study with a mean follow-up duration of 15 months (range: 4-27 months). The mean Oxford shoulder score improved by 13 points (95% confidence interval [CI]: 11-15 points). The mean health utility gain extrapolated from the EQ-5DTM questionnaire improved by 0.23 (95% CI: 0.16-0.30), translating to a minimum cost per QALY of L5,683. CONCLUSIONS: Subacromial decompression leads to significant improvement in function and quality of life in a cost effective manner. This provides justification for its ongoing practice by appropriately trained shoulder surgeons in correctly selected patients. PMID- 26263809 TI - Selective conservatism in the management of thoracic trauma remains appropriate in the 21st century. AB - INTRODUCTION: Selective conservatism for thoracic trauma is well established but the emergence of new technologies may cause management strategies to continue to evolve. METHODS: A retrospective study was conducted on thoracic trauma patients managed in a single institution in South Africa over a 4-year period to determine the appropriateness of our current policy of selective conservatism. RESULTS: A total of 1,239 patients were included in the study; 112 required an emergency thoracotomy, 125 were admitted for observation and 1,002 required a tube thoracostomy (TT). Ninety-one per cent of the patients were male and the median age was 24 years. Seventy-five per cent of the cases were penetrating trauma and the remaining were blunt trauma. The indications for TT were pneumothorax (PTX) (n=382, 38%), haemothorax (HTX) (n=300, 30%) and haemopneumothorax (HPTX) (n=320, 32%). A total of 13% (127/1,002) of all chest x-rays (CXR) following tube removal demonstrated residual pathologies that precluded immediate discharge: 32 (8%) in Group A (PTX), 44 (15%) in Group B (HTX) and 51 (16%) in Group C (HPTX). All 32 patients in Group A were simply observed and did not require further intervention. In Group B, 17 patients required repeat TTs and 27 required video assisted thoracoscopic surgery (VATS) for clearance of residual HTX. Twenty-nine patients in Group C required repeat TTs and twenty-two required VATS. CONCLUSIONS: The vast majority of patients with thoracic trauma can be managed conservatively with TT alone. Residual pathology appeared to be lowest in patients with a PTX, which seldom requires treatment, while only a minority of patients required repeat TTs or VATS for a retained HTX. Selective conservatism is still appropriate in the current era in a developing world setting. PMID- 26263810 TI - Incidence and survival trends of lip, intra-oral cavity and tongue base cancers in south-east England. AB - BACKGROUND: Oral cavity cancers are on the increase in the UK. Understanding site specific epidemiological trends is important for cancer control measures. This study demonstrates the changing epidemiological trends in lip, intra-oral cavity and tongue base cancers in south-east England from 1987 to 2006. AIM: METHODS: This was a retrospective study using anonymised data obtained from the Thames Cancer Registry (TCR) London. Data were analysed using SPSS v.17 and survival analyses with Kaplan-Meier and Cox regression. Age standardisation of the incidence rates was performed. It was conducted in south-east England, which has an average population of 12 million. The study analysed 9,318 cases (ICD-10 code C00-C06, C14). Kent Research Ethics Committee UK granted ethical approval. RESULTS: Oral cancers were more common in men, with male: female ratio of 1.6:1. Tongue cancers had the highest frequency at 3,088 (33.1%). Incidence varied with each cancer type. Mean incidence (per 1,000,000) ranged from 2.3 (lip cancer) to 13.8 (tongue cancer). There has been a statistically significant increase in incidence for cancers of the tongue base, other parts of tongue, gum and palate (p<0.001). Median survival time varied by sub-site, with lip cancer having the best median survival time (11.09 years) compared with tongue base cancer (2.42 years). Survival analyses showed worse prognosis for men, older age at diagnosis, and presence of synchronous tumours (p<0.001). CONCLUSION: There is a rising incidence of tongue and tongue base, gum and palate cancers in south-east England with wide variability in survival. Oral cancer awareness and screening programmes should be encouraged. PMID- 26263811 TI - Tier 3 multidisciplinary medical weight management improves outcome of Roux-en-Y gastric bypass surgery. AB - INTRODUCTION: In 2013 the Department of Health specified eligibility for bariatric surgery funded by the National Health Service. This included a mandatory specification that patients first complete a Tier 3 medical weight management programme. The clinical effectiveness of this recommendation has not been evaluated previously. Our bariatric centre has provided a Tier 3 programme six months prior to bariatric surgery since 2009. The aim of our retrospective study was to compare weight loss in two cohorts: Roux-en-Y gastric bypass only (RYGB only cohort) versus Tier 3 weight management followed by RYGB (Tier 3 cohort). METHODS: A total of 110 patients were selected for the study: 66 in the RYGB only cohort and 44 in the Tier 3 cohort. Patients in both cohorts were matched for age, sex, preoperative body mass index and pre-existing co morbidities. The principal variable was therefore whether they undertook the weight management programme prior to RYGB. Patients from both cohorts were followed up at 6 and 12 months to assess weight loss. RESULTS: The mean weight loss at 6 months for the Tier 3 cohort was 31% (range: 18-69%, standard deviation [SD]: 0.10 percentage points) compared with 23% (range: 4-93%, SD: 0.12 percentage points) for the RYGB only cohort (p=0.0002). The mean weight loss at 12 months for the Tier 3 cohort was 34% (range: 17-51%, SD: 0.09 percentage points) compared with 27% (range: 14-48%, SD: 0.87 percentage points) in the RYGB only cohort (p=0.0037). CONCLUSIONS: Our study revealed that in our matched cohorts, patients receiving Tier 3 specialist medical weight management input prior to RYGB lost significantly more weight at 6 and 12 months than RYGB only patients. This confirms the clinical efficacy of such a weight management programme prior to gastric bypass surgery and supports its inclusion in eligibility criteria for bariatric surgery. PMID- 26263812 TI - A simple technique to achieve parallel transverse cuts in the scarf osteotomy. PMID- 26263813 TI - How to measure distal locking screws for intramedullary nails without a depth gauge. PMID- 26263814 TI - Fine-tuning of blocking screws in long bone nailing. PMID- 26263815 TI - Packing of the pelvis following abdominoperineal excision of the rectum. PMID- 26263816 TI - Combined endoscopic approach for patients with multiple bladder stones. PMID- 26263817 TI - Avoiding open reduction and internal fixation in the intramedullary nailing of subtrochanteric femoral fractures. PMID- 26263818 TI - Use of anterior cruciate ligament guide in Lisfranc injury fixation. PMID- 26263819 TI - Soft plastic snugger to assist seating of prosthetic aortic valve. PMID- 26263820 TI - Variations in selective nerve root block technique. PMID- 26263821 TI - Authors' response. PMID- 26263822 TI - Computed tomography of the lumbar spine. PMID- 26263823 TI - Surgical repair of pulmonary vein injury from blunt trauma. AB - Pulmonary vein deceleration injury is rare and patients can be deceptively stable for a period after injury. Quick diagnosis and transfer to the operating theatre is the only way to treat this potentially lethal injury successfully. Techniques of repair are a useful addition to the cardiovascular surgeon's repertoire. PMID- 26263824 TI - Two cases of Klebsiella pneumoniae liver abscess necessitating liver resection for effective treatment. AB - We report two British cases of liver abscess, due to Klebsiella pneumoniae and associated with synchronous infection elsewhere, which required liver resection for definitive treatment. They illustrate the geographic spread of aggressive K pneumoniae liver infection and demonstrate the importance of early aggressive treatment. PMID- 26263825 TI - Delay in diagnosis and lessons learnt from a case of abdominal wall abscess caused by fishbone perforation. AB - Complications following foreign body (FB) ingestion are an uncommon clinical problem. A 59-year-old man presented with a 4-week history of left iliac fossa pain and 1 episode of dark red blood mixed with stools. Inflammatory markers were elevated, and computed tomography (CT) of the abdomen and pelvis showed an ill defined abdominal wall inflammatory collection in close contact with the small bowel loops. He was treated with antibiotics, and follow-up CT, colonoscopy and small bowel enema were mostly unremarkable. The patient presented again ten months later with left iliac fossa cellulitis and fever. Multiplanar CT (the patient's fourth scan) demonstrated a 10cm abdominal wall collection with a linear hyperdense structure in the collection. The radiologists suspected a FB and on close scrutiny of the previous scans, they noted it to have been present on all of them. A targeted incision led to the removal of a 3cm fishbone from the collection. This case highlights the need to consider the possibility of a FB being the underlying cause in any unexplained intra-abdominal or abdominal wall inflammatory process so that the diagnosis is made in a timely manner. PMID- 26263826 TI - A clinical conundrum with a radiological answer. AB - An 82-year-old woman with longstanding medial thigh pain presented with a 5-day history of constipation, vomiting, abdominal pain and distension. She was unable to pass flatus for the preceding 24 hours and had a past history of laparoscopic abdominal surgery. Computed tomography of the abdomen and pelvis revealed a right sided obturator hernia containing a dilated loop of small bowel. She underwent emergency surgery for a right obturator hernia repair by limited laparotomy and was discharged after an extended stay complicated by postoperative atrial fibrillation. PMID- 26263827 TI - Laparoscopic management of terminal ileal volvulus caused by Meckel's diverticulum. AB - Complications from a Meckel's diverticulum include diverticulitis, bleeding, intussusception, bowel obstruction, a volvulus, a vesicodiverticular fistula, perforation or very rarely as a tumour. We report a case where a Meckel's diverticulum presented with a terminal ileal volvulus in a 32-year-old man without the presence of a typical vitelline band or axial torsion of the diverticulum causing the volvulus. It was successfully managed laparoscopically. PMID- 26263828 TI - Upper airway obstruction in a patient with Ehlers-Danlos syndrome. AB - We report a case of recurrent airway obstruction episodes resulting from laryngeal hypermobility in a patient with Ehlers-Danlos syndrome. A 44-year-old woman, with known Ehlers-Danlos syndrome, presented with recent onset of episodes of upper airway obstruction due to hypermobility of her larynx. A suitable conservative management strategy proved elusive and the patient finally underwent a thyrohyoidopexy. The patient remains symptom free nine months after the procedure. This is the first report of spontaneous life threatening upper airway obstruction due to hypermobility of the suprahyoid suspensory soft tissues in Ehlers-Danlos syndrome. PMID- 26263829 TI - Bio-hybrid interfaces to study neuromorphic functionalities: New multidisciplinary evidences of cell viability on poly(anyline) (PANI), a semiconductor polymer with memristive properties. AB - The interfacing of artificial devices with biological systems is a challenging field that crosses several disciplines ranging from fundamental research (biophysical chemistry, neurobiology, material and surface science) to frontier technological application (nanotechnology, bioelectronics). The memristor is the fourth fundamental circuit element, whose electrical properties favor applications in signal processing, neural networks, and brain-computer interactions and it represents a new frontier for technological applications in many fields including the nanotechnologies, bioelectronics and the biosensors. Using multidisciplinary approaches, covering surface science, cell biology and electrophysiology, we successfully implemented a living bio-hybrid system constituted by cells adhering to films of poly(aniline) (PANI), a semiconductor polymer having memristive properties assembled with polyelectrolytes. Here we tested whether the PANI devices could support survivor, adhesion and differentiation of several cell lines, including the neuron-like SHSY5Y cells. Moreover, we performed electrophysiology on these cells showing that the biophysical properties are retained with differences occurring in the recorded ion currents. Taken together, the cell viability here reported is the key requirement to design and develop a reliable functional memristor-based bio hybrid able to mimic neuronal activity and plasticity. PMID- 26263830 TI - Clinical Outcomes in Cardiac Arrest Patients Following Prehospital Treatment with Therapeutic Hypothermia. AB - INTRODUCTION: Recent studies have brought to question the efficacy of the use of prehospital therapeutic hypothermia for victims of out-of-hospital cardiac arrest (OHCA). Though guidelines recommend therapeutic hypothermia as a critical link in the chain of survival, the safety of this intervention, with the possibility of minimal treatment benefit, becomes important. Hypothesis/Problem This study examined prehospital therapeutic hypothermia for OHCA, its association with survival, and its complication profile in a large, metropolitan, fire-based Emergency Medical Services (EMS) system, where bystander cardiopulmonary resuscitation (CPR) and post-arrest care are in the process of being optimized. METHODS: This evaluation was a retrospective chart review of all OHCA patients with return of spontaneous circulation (ROSC) treated with therapeutic hypothermia, from January 1, 2013 through November 30, 2013. The primary outcomes were the proportion of patients with initiation of prehospital therapeutic hypothermia with survival to hospital admission, the proportion of patients with initiation of prehospital therapeutic hypothermia with survival to hospital discharge, and the complication profile of therapeutic hypothermia in this population. The complication profile included several clinical, radiographic, and laboratory parameters. Exclusion criteria included: no prehospital therapeutic hypothermia initiation; no ROSC; and age of 17 year old or younger. RESULTS: Fifty-one post-cardiac arrest patients were identified that met inclusion criteria. The mean age was 61 years (SD=14.7 years), and 33 (72%) were male. The initial rhythm was ventricular fibrillation or pulseless ventricular tachycardia in 17 (37%) patients, and bystander CPR was performed in 28 (61%) patients with ROSC. Thirty-nine (85%) patients survived to hospital admission. Twenty-one patients (48%; 95% CI, 33-64) were administered vasopressors, 10 patients (24%; 95% CI, 10-37) were administered diuretics, and 19 patients (44%; 95% CI, 29-60) were administered antibiotics. Initial chest radiograph (CXR) findings were normal in 12 (29%) patients. Overall, 13 (28%; 95% CI, 15-42) study patients survived to hospital discharge. CONCLUSION: Recent reports have questioned the efficacy and safety of prehospital therapeutic hypothermia. In this evaluation, in the setting of unstandardized post-arrest care, 85% of the patients survived to hospital admission and 28% survived to hospital discharge, with a complication profile which was similar to that noted in other studies. This suggests that further evidence may be needed before EMS systems stop administering therapeutic hypothermia to appropriately selected patients. In less-optimized systems, therapeutic hypothermia may still be an essential link in the chain of survival. PMID- 26263831 TI - Momentum sequence and environmental climate influence levels of perceived psychological momentum within a sport competition. AB - The present study examined the influence of momentum sequence (positive vs. negative) and environmental climate (hot-wet vs. neutral) on supporters' (i.e. virtual observers') reported levels of perceived psychological momentum (PM) during a simulated cycling competition. Participants supported one of two competing cyclists involved in a race that was displayed on a screen in a lecture hall. The race scenario was manipulated so that the supported cyclist appeared to undergo either a positive or negative momentum sequence. In addition, participants were either exposed to a hot-wet environmental climate or to a neutral environmental climate while observing the race scenario. According to the results, reported levels of PM were higher in the positive momentum sequence condition than in the negative momentum sequence condition, consistent with the notion that supporters' PM is influenced by a positivity bias, and reported levels of PM were also found to be higher in the hot-wet climate condition than in the neutral climate condition, consistent with the notion that environmental climate is a contextual factor that influences PM through the operation of a causal augmenting mechanism. PMID- 26263833 TI - Crystalloid administration among patients undergoing liver surgery: Defining patient- and provider-level variation. AB - BACKGROUND: Fluid administration among patients undergoing liver resection is a key aspect of perioperative care. We sought to examine practice patterns of crystalloid administration, as well as potential factors associated with receipt of crystalloid fluids. METHOD: Patients who underwent liver resection between 2010 and 2014 were identified. Data on clinicopathologic variables, operative details, and perioperative fluid administration were collected and analyzed using univariable and multivariable analyses; variation in practice of crystalloid administration was presented as coefficient of variation (COV). RESULTS: Among 487 patients, median crystalloid administered at the time of surgery was 4,000 mL. After adjusting for body size and operative duration, median corrected crystalloid was 30.0 mL kg(-1) m(2) h(-1), corresponding with a COV of 35%. Patients who received <30 mL kg(-1) m(2) h(-1) crystalloids were more likely to be younger (58 vs 60 years), white (79% vs 74%), and have a higher body mass index (BMI; 28.2 vs 25.4 kg/m(2); all P < .001). On multivariable analysis, increasing Charlson comorbidity index, BMI, estimated blood loss, and each additional hour of surgery were all associated with increased crystalloid administration (all P < .05). Corrected crystalloid administration varied among providers with a corrected COV ranging from 14% to 61%. When overall variation in crystalloid administration was assessed, 80% of the variation occurred at the patient level, and 20% occurred at the provider level (surgeon, 3% vs anesthesiologist, 17%). CONCLUSION: There was wide variability in crystalloid administration among patients undergoing liver resection. Although the majority of variation was attributable to patient factors, a large amount of residual variation was attributable to provider-level differences. PMID- 26263832 TI - Hemorrhoids and matrix metalloproteinases: A multicenter study on the predictive role of biomarkers. AB - INTRODUCTION: An association between hemorrhoidal disease and matrix metalloproteinases (MMPs) has been described previously. MMPs regulate extracellular structural proteins and tissue remodeling. Neutrophil gelatinase associated lipocalin (NGAL) is involved in the regulation of MMP activity. The aim of this work was to study the relationship between tissue immunoreactive levels of MMPs and NGAL and different stages of hemorrhoids. METHODS: In a multicenter, open-label, prospective study, the population under investigation consisted of 2 groups: group I (with symptomatic hemorrhoids; Goligher grade I IV) and group II (healthy volunteers). RESULTS: We enrolled 97 patients with hemorrhoids: 21 with grade I hemorrhoids, 37 with grade II, 14 with grade III, and 25 with grade IV. Finally, 90 healthy volunteers (53 males and 37 females; age range, 19-70 years; median, 56) were enrolled in group II. Enzyme-linked immunosorbent assay and Western blot analysis revealed greater levels of immunoreactive MMPs and NGAL in all patients with hemorrhoids. We recorded significantly greater levels of MMP-1 and MMP-3 in grade I and II patients compared with control, and greater levels of MMP-3, MMP-7, MMP-8, and MMP-9 in grade III compared with grade II. MMP-9 and NGAL were particularly increased in patients with grade IV especially in case of thrombosed hemorrhoids. CONCLUSION: These results provide potentially important insights into the understanding of the natural history of hemorrhoids. MMPs and NGAL play a role in development of disease and may represent molecular markers for the complications such as hemorrhoidal thrombosis. PMID- 26263834 TI - On the distribution and population dynamics of the ctenophore Mnemiopsis leidyi in the Belgian part of the North Sea and Westerschelde estuary. AB - The spatio-temporal distribution and population dynamics of the non-indigenous ctenophore Mnemiopsis leidyi A. Agassiz 1865 were investigated through monthly and quarterly surveys in 2011-2012 at several locations in the Belgian part of the North Sea, the main coastal ports and the adjacent Westerschelde estuary. M. leidyi occurred from August to December, but was never found more than 30 km offshore. Densities were generally low (average 0.8 +/- SD 2.8 ind m(-3)) compared to other invaded European systems. Highest densities of M. leidyi were found in the semi-enclosed basin (port of Oostende; 18.4 ind m(-3)) and Westerschelde estuary (1.9 ind m(-3)). The presence of larvae and sudden appearance of high numbers across the size distribution in August indicated that ports and estuaries may act as sources, populating the adjacent coastal area. The zero-inflated logistic regression model showed that there is a higher chance of finding M. leidyi (presence) when temperature declines from late summer onwards. Combined with a negative binomial regression, our model suggests that increasing M. leidyi densities are associated with decreasing autumn temperatures, low wave height (low energetic systems) and low dissolved oxygen concentrations Although densities remained relatively low since its first appearance in 2007, a permanent population seems to be established in Belgian waters. As population outbursts may occur with only a small change in environmental parameters, further monitoring of this notorious invasive species is recommended. PMID- 26263835 TI - An examination of the ingestion, bioaccumulation, and depuration of titanium dioxide nanoparticles by the blue mussel (Mytilus edulis) and the eastern oyster (Crassostrea virginica). AB - The production rates of titanium dioxide (TiO2) nanoparticles for consumer products far exceed the pace at which research can determine the effects of these particles in the natural environment. Sedentary organisms such as suspension feeding bivalves are particularly vulnerable to anthropogenic contaminants, such as nanoparticles, that enter coastal environments. The purpose of this work was to examine the ingestion, bioaccumulation, and depuration rates of TiO2 nanoparticles by two species of suspension-feeding bivalves, the blue mussel (Mytilus edulis) and the eastern oyster (Crassostrea virginica). Two representative TiO2 nanoparticles, UV-Titan M212 (Titan) and Aeroxide P25 (P25), were delivered to the animals either incorporated into marine snow or added directly to seawater at a concentration of 1.0 mg/L for exposure periods of 2 and 6 h. After feeding, the animals were transferred to filtered-seawater and allowed to depurate. Feces and tissues were collected at 0, 12, 24, 72, and 120 h, post exposure, and analyzed for concentrations of titanium by inductively coupled plasma-mass spectrometry. Results indicated that the capture and ingestion (i.e., transfer to the gut) of TiO2 nanoparticles by both mussels and oysters was not dependent on the presence of marine snow, and weight-standardized clearance rates of bivalves exposed to TiO2 nanoparticles were not significantly different than those of unexposed control animals. Both species ingested about half of the nanoparticles to which they were exposed, and >90% of the nanoparticles were egested in feces within 12 h, post-exposure. The findings of this study demonstrate that mussels and oysters can readily ingest both Titan and P25 nanoparticles regardless of the form in which they are encountered, but depurate these materials over a short period of time. Importantly, bioaccumulation of Titan and P25 nanoparticles does not occur in mussels and oysters following exposures of up to 6 h. PMID- 26263836 TI - Genetic diversity and genetic structure of the striped field mouse Apodemus agrarius coreae (Muridae, Rodentia) in Korea. AB - The aim of this study was to investigate the genetic diversity and genetic structure of the striped field mouse Apodemus agrarius coreae in Korea. The Korean A. a. coreae is characterized by high levels of haplotype diversity (Hd=0.967) and low levels of nucleotide diversity (pi=0.00683). Haplogroup 1 is well separated from the haplotypes of the neighboring regions of the Korean Peninsula, while the other haplogroups are closely related to those from the Russian Far East. Thus, further investigations are required to confirm the validity of the subspecies status of A. a. coreae by implementing additional morphological characters as well as genetic data from the populations present in the Korean Peninsula and its neighboring countries. Haplogroup 1 includes most Korean haplotypes and forms a star-like haplotype network structure, which reveals relatively low levels of sequence divergence and high frequency of unique mutations (only few mutations are shared in most of the haplotype nodes). The results indicate that the haplotypes of Haplogroup 1 might have experienced population expansion since their migration into Korea, which was further corroborated with negative results of neutrality tests for Korean population of A. a. coreae. PMID- 26263837 TI - Glenohumeral joint kinematics measured by intracortical pins, reflective markers, and computed tomography: A novel technique to assess acromiohumeral distance. AB - Combination of biplane fluoroscopy and CT-scan provides accurate 3D measurement of the acromiohumeral distance (AHD) during dynamic tasks. However, participants performed only two and six trials in previous experiments to respect the recommended radiation exposure per year. Our objective was to propose a technique to assess the AHD in 3D during dynamic tasks without this limitation. The AHD was computed from glenohumeral kinematics obtained using markers fitted to pins drilled into the scapula and the humerus combined with 3D bone geometry obtained using CT-scan. Four participants performed range-of-motion, daily-living, and sports activities. Sixty-six out of 158trials performed by each participant were analyzed. Two participants were not considered due to experimental issues. AHD decreased with arm elevation. Overall, the smallest AHD occurred in abduction (1.1mm (P1) and 1.2mm (P2)). The smallest AHD were 2.4mm (P1) and 3.1mm (P2) during ADL. It was 2.8mm (P1) and 1.1mm (P2) during sports activities. The humeral head greater and lesser tuberosities came the nearest to the acromion. The proposed technique increases the number of trials acquired during one experiment compared to previous. The identification of movements maximizing AHD is possible, which may provide benefits for shoulder rehabilitation. PMID- 26263838 TI - Noninvasive assessment of the activity of the shoulder girdle muscles using ultrasound real-time tissue elastography. AB - The purpose of this study was to clarify whether the activity of the shoulder girdle muscles could be estimated by measuring the elasticity of these muscles under several levels of muscle contraction through ultrasound real-time tissue elastography (RTE). Ten healthy men performed submaximal voluntary contractions (MVC) in each manual muscle testing position for the middle deltoid, upper trapezius, supraspinatus, levator scapulae, and rhomboid major. The elasticity of these muscles was measured using ultrasound RTE during the task. The strain ratio of the muscle to an acoustic coupler was calculated as an assessment index of the muscle elasticity. Higher strain ratio values imply lower elasticity. In addition, the electromyographic activity was recorded from surface electrodes attached only to the middle deltoid and upper trapezius. The strain ratios were negatively correlated with the normalized root mean square values for the middle deltoid (r=-0.659, p<0.001) and upper trapezius (r=-0.554, p<0.001). The strain ratios of all the muscles decreased with an increase from 10% MVC force to 30% MVC force. Ultrasound RTE may be useful for noninvasively assessing the activity of the shoulder girdle muscles at certain shoulder positions with low levels of muscle contraction. PMID- 26263840 TI - Introduction: Supramolecular Chemistry. PMID- 26263839 TI - Functional hemispherectomy: postoperative motor state and correlation to preoperative DTI. AB - INTRODUCTION: Functional hemispherectomy (FH) is an infrequent method to reduce seizure frequency in patients with intractable epilepsy. The risk that hemispherotomy injures brain structures involved in residual motor function is challenging to predict. Our purpose was to evaluate MR diffusion tensor imaging (DTI) to preoperatively assess residual ipsilateral motor function prior to FH. METHODS: We applied DTI in 34 patients scheduled for FH to perform fiber tracking in healthy and damaged hemispheres of the corticospinal tracts (CSTs) and of the corpus callosum. We assessed the CSTs and the commissural fibers for streamline count, for fractional anisotropy (FA), and for respective ratios (affected/unaffected side). We correlated these DTI values to post-to-prior changes of muscle strength and evaluated their diagnostic accuracy. RESULTS: FA of the affected CSTs and of commissural fibers was significantly higher in patients with postoperative loss of muscle strength compared to patients without (p = 0.014 and p = 0.008). In contrast, CST FA from healthy hemispheres was not different between both groups. Ratios of streamline counts and FA from CSTs were higher in patients with postoperative reduced muscle strength compared to those without (1.14 +/- 0.22 vs. 0.58 +/- 0.14, p = 0.040; 0.93 +/- 0.05 vs. 0.74 +/- 0.03, p = 0.003). CSTs' normalized FA ratio greater than -0.085 predicted loss of muscle strength with 80 % sensitivity and 69.6 % specificity. CONCLUSION: Preoperative tracking of the CST and of commissural fibers contributes to the prediction of postoperative motor outcome after functional hemispherectomy. PMID- 26263841 TI - Congenital isolated cleft mitral valve leaflet and apical muscular ventricular septal defect in a Holstein calf. AB - A 5-week-old Holstein heifer calf presented for emergency treatment of signs referable to gastrointestinal disease and hypovolemic shock. Fluid resuscitation uncovered clinical signs of primary cardiac disease and echocardiography revealed multiple congenital cardiac defects. Malformations included a cleft anterior mitral valve leaflet resembling an isolated cleft mitral valve and an apically located muscular ventricular septal defect. The echocardiographic and postmortem findings associated with these defects are presented and discussed in this report. PMID- 26263842 TI - Myocardial infarct associated with a partial thickness left atrial tear in a dog with mitral insufficiency. AB - A 10-year-old male neutered cavalier King Charles Spaniel with a 1-year history of degenerative mitral valve disease presented for dyspnea and severe weakness. He was diagnosed with congestive heart failure, systolic dysfunction, presumptive myocardial infarction and a left atrial thrombus based on thoracic radiographs, electrocardiogram and echocardiographic findings. Clinical signs also suggested right foreleg embolism. The dog was euthanized due to the grave prognosis and a postmortem evaluation was performed. The postmortem examination confirmed myocardial infarction and was thought to be due to embolic showering from the thrombus attached to a partial thickness left atrial endocardial tear. PMID- 26263845 TI - 2015-2016 Headache Assistant Editors. PMID- 26263844 TI - Activating Aluminum Reactivity with Fluoropolymer Coatings for Improved Energetic Composite Combustion. AB - Aluminum (Al) particles are passivated by an aluminum oxide (Al2O3) shell. Energetic blends of nanometer-sized Al particles with liquid perfluorocarbon based oxidizers such as perfluoropolyethers (PFPE) excite surface exothermic reaction between fluorine and the Al2O3 shell. The surface reaction promotes Al particle reactivity. Many Al-fueled composites use solid oxidizers that induce no Al2O3 surface exothermicity, such as molybdenum trioxide (MoO3) or copper oxide (CuO). This study investigates a perfluorinated polymer additive, PFPE, incorporated to activate Al reactivity in Al-CuO and Al-MoO3. Flame speeds, differential scanning calorimetry (DSC), and quadrupole mass spectrometry (QMS) were performed for varying percentages of PFPE blended with Al/MoO3 or Al/CuO to examine reaction kinetics and combustion performance. X-ray photoelectron spectroscopy (XPS) was performed to identify product species. Results show that the performance of the thermite-PFPE blends is highly dependent on the bond dissociation energy of the metal oxide. Fluorine-Al-based surface reaction with MoO3 produces an increase in reactivity, whereas the blends with CuO show a decline when the PFPE concentration is increased. These results provide new evidence that optimizing Al combustion can be achieved through activating exothermic Al surface reactions. PMID- 26263846 TI - Phase diagram, mechanical properties, and electronic structure of Nb-N compounds under pressure. AB - Niobium-nitrogen compounds, which are potential candidates for superhard multifunctional materials, may possess multiple stoichiometries and structures under pressure. Based on ab initio evolutionary structural searches, we predict three ground states (oP6-Nb2N, CW-NbN, and hP22-Nb5N6) and six stable high pressure phases (epsilon-NbN, AsNi-NbN, U2S3-Nb2N3, oC24-NbN2, mP8-NbN3, and mP20 NbN4) for Nb-N compounds at pressures up to 100 GPa. Among them, the oP6-Nb2N, oC24-NbN2, mP8-NbN3, and mP20-NbN4 have never been reported, and N-rich oC24 NbN2, mP8-NbN3, and mP20-NbN4 high pressure phases are recoverable to ambient pressure. We find that the structure of N-rich Nb-N compounds consists of NbNx polyhedral stacking configurations and connected with Nn (n = 2, 3, 4, and n) polymerizations, which can remarkably improve the elastic modulus. It is found that CW-NbN and mP20-NbN4 are two potential ultra-incompressible and hard materials with the hardness calculated to be 24.56 and 19.86 GPa, respectively, while other N-rich phases such as U2S3-Nb2N3, oC24-NbN2, and mP8-NbN3 are soft materials. Detailed electronic structure and chemical bonding analysis proved that the high hardness of CW-NbN and mP20-NbN4 stems from the strong covalent bonding and the fullfilled Nb-N bonding and antibonding states. PMID- 26263847 TI - Author's Reply to Comment on "Age as a Prognostic Factor in Patients with Acute Coronary Syndrome Undergoing Urgent/Emergency Cardiac Surgery". PMID- 26263843 TI - Age decreases macrophage IL-10 expression: Implications for functional recovery and tissue repair in spinal cord injury. AB - Macrophages with different activation states are present after spinal cord injury (SCI). M1 macrophages purportedly promote secondary injury processes while M2 cells support axon growth. The average age at the time of SCI has increased in recent decades, however, little is known about how different physiological factors contribute to macrophage activation states after SCI. Here we investigate the effect of age on IL-10, a key indicator of M2 macrophage activation. Following mild-moderate SCI in 4 and 14 month old (MO) mice we detected significantly reduced IL-10 expression with age in the injured spinal cord. Specifically, CD86/IL-10 positive macrophages, also known as M2b or regulatory macrophages, were reduced in 14 vs. 4 MO SCI animals. This age-dependent shift in macrophage phenotype was associated with impaired functional recovery and enhanced tissue damage in 14-month-old SCI mice. In vitro, M2b macrophages release anti-inflammatory cytokines without causing neurotoxicity, suggesting that imbalances in the M2b response in 14-month-old mice may be contributing to secondary injury processes. Our data indicate that age is an important factor that regulates SCI inflammation and recovery even to mild-moderate injury. Further, alterations in macrophage activation states may contribute to recovery and we have identified the M2b phenotype as a potential target for therapeutic intervention. PMID- 26263850 TI - The photoirradiation induced p-n junction in naphthylamine-based organic photovoltaic cells. AB - The bulk heterojunction (BHJ) plays an indispensable role in organic photovoltaics, and thus has been investigated extensively in recent years. While a p-n heterojunction is usually fabricated using two different donor and acceptor materials such as poly(3-hexylthiophene-2,5-diyl) (P3HT) and phenyl-C61-butyric acid methyl ester (PCBM), it is really rare that such a BHJ is constructed by a single entity. Here, we presented a photoirradiation-induced p-n heterojunction in naphthylamine-based organic photovoltaic cells, where naphthylamine as a typical p-type semiconductor could be oxidized under photoirradiation and transformed into a new semiconductor with the n-type character. The p-n heterojunction was realized using both the remaining naphthylamine and its oxidative product, giving rise to the performance improvement in organic photovoltaic devices. The experimental results show that the power conversion efficiency (PCE) of the devices could be achieved up to 1.79% and 0.43% in solution and thin film processes, respectively. Importantly, this technology using naphthylamine does not require classic P3HT and PCBM to realize the p-n heterojunction, thereby simplifying the device fabrication process. The present approach opens up a promising route for the development of novel materials applicable to the p-n heterojunction. PMID- 26263848 TI - Professional risks when carrying out cytoreductive surgery for peritoneal malignancy with hyperthermic intraperitoneal chemotherapy (HIPEC): A French multicentric survey. AB - BACKGROUND: Over the last two decades, many surgical teams have developed programs to treat peritoneal carcinomatosis with extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Currently, there are no specific recommendations for HIPEC procedures concerning environmental contamination risk management, personal protective equipment (PPE), or occupational health supervision. METHODS: A survey of the institutional practices among all French teams currently performing HIPEC procedures was carried out via the French network for the treatment of rare peritoneal malignancies (RENAPE). RESULTS: Thirty three surgical teams responded, 14 (42.4%) which reported more than 10 years of HIPEC experience. Some practices were widespread, such as using HIPEC machine approved by the European Community (100%), individualized or centralized smoke evacuation (81.8%), "open" abdominal coverage during perfusion (75.8%), and maintaining the same surgeon throughout the procedure (69.7%). Others were more heterogeneous, including laminar flow air circulation (54.5%) and the provision of safety protocols in the event of perfusate spills (51.5%). The use of specialized personal protective equipment is ubiquitous (93.9%) but widely variable between programs. CONCLUSION: Protocols regarding cytoreductive surgery/HIPEC and the associated professional risks in France lack standardization and should be established. PMID- 26263849 TI - Design and Characterization of a Sensorized Microfluidic Cell-Culture System with Electro-Thermal Micro-Pumps and Sensors for Cell Adhesion, Oxygen, and pH on a Glass Chip. AB - We combined a multi-sensor glass-chip with a microfluidic channel grid for the characterization of cellular behavior. The grid was imprinted in poly-dimethyl siloxane. Mouse-embryonal/fetal calvaria fibroblasts (MC3T3-E1) were used as a model system. Thin-film platinum (Pt) sensors for respiration (amperometric oxygen electrode), acidification (potentiometric pH electrodes) and cell adhesion (interdigitated-electrodes structures, IDES) allowed us to monitor cell physiological parameters as well as the cell-spreading behavior. Two on-chip electro-thermal micro-pumps (ETMUPs) permitted the induction of medium flow in the system, e.g., for medium mixing and drug delivery. The glass-wafer technology ensured the microscopic observability of the on-chip cell culture. Connecting Pt structures were passivated by a 1.2 MUm layer of silicon nitride (Si3N4). Thin Si3N4 layers (20 nm or 60 nm) were used as the sensitive material of the pH electrodes. These electrodes showed a linear behavior in the pH range from 4 to 9, with a sensitivity of up to 39 mV per pH step. The oxygen sensors were circular Pt electrodes with a sensor area of 78.5 MUm(2). Their sensitivity was 100 pA per 1% oxygen increase in the range from 0% to 21% oxygen (air saturated). Two different IDES geometries with 30- and 50-MUm finger spacings showed comparable sensitivities in detecting the proliferation rate of MC3T3 cells. These cells were cultured for 11 days in vitro to test the biocompatibility, microfluidics and electric sensors of our system under standard laboratory conditions. PMID- 26263851 TI - Broiler chicken adipose tissue dynamics during the first two weeks post-hatch. AB - Selection of broiler chickens for growth has led to increased adipose tissue accretion. To investigate the post-hatch development of adipose tissue, the abdominal, clavicular, and subcutaneous adipose tissue depots were collected from broiler chicks at 4 and 14 days post-hatch. As a percent of body weight, abdominal fat increased (P<0.001) with age. At day 4, clavicular and subcutaneous fat depots were heavier (P<0.003) than abdominal fat whereas at day 14, abdominal and clavicular weighed more (P<0.003) than subcutaneous fat. Adipocyte area and diameter were greater in clavicular and subcutaneous than abdominal fat at 4 and 14 days post-hatch (P<0.001). Glycerol-3-phosphate dehydrogenase (G3PDH) activity increased (P<0.001) in all depots from day 4 to 14, and at both ages was greatest in subcutaneous, intermediate in clavicular, and lowest in abdominal fat (P<0.05). In clavicular fat, peroxisome proliferator-activated receptor-gamma (PPARgamma), CCAAT/enhancer binding protein (CEBP)alpha, CEBPbeta, fatty acid synthase (FASN), fatty acid binding protein 4 (FABP4), lipoprotein lipase (LPL), neuropeptide Y (NPY), and NPY receptor 5 (NPYR5) mRNA increased and NPYR2 mRNA decreased from day 4 to 14 (P<0.001). Thus, there are site-specific differences in broiler chick adipose development, with larger adipocytes and greater G3PDH activity in subcutaneous fat at day 4, more rapid growth of abdominal fat, and clavicular fat intermediate for most traits. Adipose tissue expansion was accompanied by changes in gene expression of adipose-associated factors. PMID- 26263852 TI - Physiological and behavioral responses of the invasive amphipod, Dikerogammarus villosus, to ammonia. AB - We studied the physiological and behavioral responses of the Ponto-Caspian amphipod Dikerogammarus villosus during exposure to four total ammonia concentrations (NH3+NH4(+); TotAmm): 0.003 (control), 0.06, 1.6, and 7.0 mmol L( 1) (0.042, 0.84, 22.4, and 98.0 mg L(-1)) for a period of up to 12 h at 21 degrees C. During the transition period from the control to treatment concentration as well as during the first hour of exposure to 0.06 and 1.6 mmol L(-1), gammarids increased their locomotor activity, which was manifested in significantly higher routine metabolic rates compared to control conditions. At control conditions, the resting metabolic rate amounted to 0.98+/-0.26 mW g(-1) and significantly increased by 19 and 37% at 0.06 and 1.6 mmol L(-1), respectively. The highest examined [TotAmm] caused a rapid and significant increase in resting metabolic rate by 37% within the first 4 h of exposure before gammarids died. The exposure to elevated [TotAmm] also resulted in a significant decreased RNA:DNA ratio and significantly higher glycogen concentrations compared to the control. We conclude that even a short exposure to TotAmm of 0.06 mmol L( 1), which may occur in natural habitats, disturbs the physiology and behavior of D. villosus and leads to increased metabolic costs of the maintenance and reduced protein synthesis. PMID- 26263853 TI - Dynamics of blood viscosity regulation during hypoxic challenges in the chicken embryo (Gallus gallus domesticus). AB - Hypoxia in chicken embryos increases hematocrit (Hct), blood O2 content, and blood viscosity. The latter may limit O2 transport capacity (OTC) via increased peripheral resistance. Hct increase may result from increased nucleated red blood cell concentration ([RBC]) and mean corpuscular volume (MCV) or reduced plasma volume. We hypothesized changes in Hct, hemoglobin concentration ([Hb]), [RBC] and MCV and their effects on viscosity would reduce OTC. Five experimental treatments that increase Hct were conducted on day 15 embryos: 60min water submergence with 60min recovery in air; exposure to 15% O2 with or without 5% CO2 for 24 h with 6 h recovery; or exposure to 10% O2 with or without 5% CO2 for 120 min with 120 min recovery. Control Hct, [Hb], [RBC], MCV, and viscosity were approximately 26%, 9g%, 2.0 10(6)MUL(-1), 130MUm(3), and 1.6mPas, respectively. All manipulations increased Hct and blood viscosity without changing blood osmolality (276mmolkg(-1)). Increased viscosity was attributed to increased [RBC] and MCV in submerged embryos, but solely MCV in embryos experiencing 10% O2 regardless of CO2. Blood viscosity in embryos exposed to 15% O2 increased via increased MCV alone, and viscosity was constant during recovery despite increased [RBC]. Consequently, blood viscosity was governed by MCV and [RBC] during submergence, while MCV was the strongest determinant of blood viscosity in extrinsic hypoxia with or without hypercapnia. Increased Hct and blood O2 content did not compensate for the effect of increased viscosity on OTC during these challenges. PMID- 26263856 TI - Caveat doctor. PMID- 26263855 TI - Stability of HIB-Cul3 E3 ligase adaptor HIB Is Regulated by Self-degradation and Availability of Its Substrates. AB - The HIB-Cul3 complex E3 ligase regulates physiological homeostasis through regulating its substrate stability and its activity can be modulated by changing HIB abundance. However, regulation of HIB remains elusive. Here we provide evidence that HIB is degraded through the proteasome by Cul3-mediated polyubiquitination in K48 manner in Drosophila. Strikingly, HIB is targeted for degradation by itself. We further identify that three degrons ((52)LKSS(56)T, (76)LDEE(80)S and (117)MESQ(121)R) and K185 and K198 of HIB are essential for its auto-degradation. Finally, we demonstrate that HIB-Cul3 substrates, Ci and Puc, can effectively protect HIB from HIB-Cul3-mediated degradation. Taken together, our study indicates that there is an exquisite equilibrium between the adaptor and targets to achieve the tight control of the HIB, which is essential for maintaining suitable Hh and JNK signaling. And the mechanism of adaptor self degradation and reciprocal control of the abundance between adaptor and its substrates is also applied to BTB-Cul3 E3 ligase adaptor dKeap1, dDiablo and dKLHL18. PMID- 26263854 TI - Chronic inflammation in urothelial bladder cancer. AB - The association between inflammation and cancer has been pointed out in epidemiological and clinical studies, revealing how chronic inflammation may contribute to carcinogenesis in various malignancies. However, the molecular events leading to malignant transformation in a chronically inflamed environment are not fully understood. In urothelial carcinoma of the urinary bladder, inflammation plays a dual role. On the one hand, chronic inflammation is a well established risk factor for the development of bladder cancer (BC), as seen in Schistosoma haematobium infection. On the other, intravesical therapy by bacillus Calmette-Guerin (BCG), which induces inflammation, offers protection against cancer recurrence. The large variety of pro-inflammatory mediators expressed by BC and immune cells binds to specific receptors which control signalling pathways. These activate transcription of a plethora of downstream factors. This review summarizes recent data regarding inflammation and urothelial carcinoma, with special emphasis on the role the inflammatory response plays in BC recurrence risk and progression. PMID- 26263857 TI - Paternalism and consent: has the law finally caught up with the profession? PMID- 26263858 TI - Glove balloons 3. PMID- 26263859 TI - Trachway video stylet use in double lumen tube insertion. PMID- 26263860 TI - Supraglottic airways as conduits for fibreoptic intubation. PMID- 26263861 TI - Use of the Macintosh laryngoscope for double-lumen tracheal tube placement. PMID- 26263862 TI - Cranial nerve injuries with supraglottic airway devices--more common than we think? PMID- 26263863 TI - Reconstituted whole blood plus fibrinogen for massive transfusion in trauma. PMID- 26263864 TI - Hyaluronidase for brachial plexus block. PMID- 26263865 TI - Propofol for caesarean section under general anaesthesia. PMID- 26263866 TI - A reply. PMID- 26263867 TI - Consultant-delivered care. PMID- 26263868 TI - Normalising lean body weight. PMID- 26263869 TI - Safe extubation in recovery rooms. PMID- 26263870 TI - Medicina syringe breakage. PMID- 26263871 TI - Standardised signage for emergency drug location. PMID- 26263872 TI - Respiratory optimisation and mobile ECMO for severe respiratory failure. PMID- 26263873 TI - High Dietary Copper Increases Catecholamine Concentrations in the Hypothalami and Midbrains of Growing Pigs. AB - The experiment was conducted to investigate the effect of high dietary copper on catecholamine concentration and dopamine-beta-hydroxylase (DbetaH) activity in hypothalami and midbrains of growing pigs. Forty-five crossbred weanling pigs with an average body weight of 7.5 kg were randomly assigned to three groups of 15 each to receive a control diet containing 10 mg/kg Cu (diet A) and diets containing 125 (diet B) or 250 (diet C) mg Cu/kg DM for 45 days. Compared to the control, Cu supplementation at both 125 and 250 mg Cu/kg DM increased average daily gain (ADG), average daily feed intake (ADFI), and feed efficiency. High dietary copper increased midbrain and hypothalami dopamine (DA) and norepinephrine (NE) concentrations and midbrain dopamine-beta-hydroxylase activity. However, increasing dietary Cu had no effect on hypothalami dopamine beta-hydroxylase activity. PMID- 26263874 TI - Surgeon-performed ultrasound: accurate, reproducible, and more efficient. AB - PURPOSE: A study previously performed at our institution demonstrated that surgeon-performed ultrasound (SPUS) was accurate compared to radiology department ultrasound (RDUS) when evaluating children with suspected appendicitis. The purpose of this study was to determine if these results were reproducible and if SPUS decreased time to definitive diagnosis. METHODS: A surgery resident performed examinations and ultrasounds on children with suspected appendicitis. Final diagnosis was confirmed by pathology. Results were compared to RDUS and combined with the previous study for a final comparison with RDUS. Mean time to diagnosis was recorded. Data were analyzed using Fisher exact and Student's t test. RESULTS: Fifty-eight patients underwent SPUS, of these 35 had RDUS. The accuracy of SPUS alone was 93% (54/58) and RDUS accuracy was 94% (33/35) (p = 1). When SPUS was combined with clinical examination accuracy increased to 95% (55/58). When results were combined with the previous study, overall accuracy of SPUS was 90% (101/112) compared to overall RDUS accuracy of 89 % (50/56). Mean time to diagnosis for RDUS was 135 min (n = 35), whereas mean time to diagnosis for SPUS was 30 min (n = 58; p = 0.0001). CONCLUSION: SPUS is accurate and reproducible in evaluating children with suspected appendicitis. SPUS potentially decreases time to definitive therapy and emergency department wait times. PMID- 26263875 TI - Benign liver tumors in children: outcomes after resection. AB - PURPOSE: Benign liver tumors in children are rare and data regarding the surgical outcomes are deficient. We reviewed our experience in the management of these tumors particularly the extent, safety, and effectiveness of surgical resection. METHODS: Between March 2005 and March 2014, 10/90 liver resections were performed for benign liver tumors. Three other patients received conservative treatment. Demographic characteristics, operative management, morbidity, and mortality were analyzed. RESULTS: The median age of the patients was 12 months. The distribution of pathology was infantile hepatic hemangioendothelioma/hemangioma (n = 7), mesenchymal hamartoma (n = 4), adenoma (n = 1) and focal nodular hyperplasia (n = 1). Median tumor size was 12.25 cm (range 3.5-21 cm) with a median tumor volume of 576.64 cm(3) (range 13.9-1822.64 cm(3)). Non-anatomic resection was performed in 6/10 patients and the median blood loss was 100 ml (range 10-850 ml). Median length of hospital stay was 7 days (range 5-9 days). There were no mortality, none of the patients had a local recurrence, and all are alive at a median follow up of 33 months. CONCLUSIONS: Two-third patients with benign liver tumors were managed with surgical excision, which comprised 11% of our resectional practice. Non-anatomical resection whenever feasible can be performed safely and does not compromise the oncological outcomes. PMID- 26263876 TI - Usefulness of Kent retractor and lifting hook for Nuss procedure. AB - Although the Nuss procedure for pectus excavatum has been widely employed, a variety of complications have been reported. The most dangerous complication is cardiac injury from the insertion of the introducer. To eliminate these complications, we present a sternum elevating technique using a Kent retractor and a lifting hook. PMID- 26263877 TI - Acclimation of fine root respiration to soil warming involves starch deposition in very fine and fine roots: a case study in Fagus sylvatica saplings. AB - Root activities in terms of respiration and non-structural carbohydrates (NSC) storage and mobilization have been suggested as major physiological roles in fine root lifespan. As more frequent heat waves and drought periods within the next decades are expected, to what extent does thermal acclimation in fine roots represent a mechanism to cope with such upcoming climatic conditions? In this study, the possible changes in very fine (diameter < 0.5 mm) and fine (0.5-1 mm) root morphology and physiology in terms of respiration rate and NSC [soluble sugars (SS) and starch] concentrations, were investigated on 2-year-old Fagus sylvatica saplings subjected to a simulated long-lasting heat wave event and to co-occurring soil drying. For both very fine and fine roots, soil temperature (ST) resulted inversely correlated with specific root length, respiration rates and SSs concentration, but directly correlated with root mass, root tissue density and starch concentration. In particular, starch concentration increased under 28 degrees C for successively decreasing under 21 degrees C ST. These findings showed that thermal acclimation in very fine and fine roots due to 24 days exposure to high ST (~ 28 degrees C), induced starch accumulation. Such 'carbon-savings strategy' should bear the maintenance costs associated to the recovery process in case of restored favorable environmental conditions, such as those occurring at the end of a heat wave event. Drought condition seems to affect the fine root vitality much more under moderate than high temperature condition, making the temporary exposure to high ST less threatening to root vitality than expected. PMID- 26263878 TI - Evaluation of an initiative to reduce radiation exposure from CT to children in a non-pediatric-focused facility. AB - We would like to share our experience of reducing pediatric radiation exposure. Much of the recent literature regarding successes of reducing radiation exposure has come from dedicated children's hospitals. Nonetheless, over the past two decades, there has been a considerable increase in CT imaging of children in the USA, predominantly in non-pediatric-focused facilities where the majority of children are treated. In our institution, two general hospitals with limited pediatric services, a dedicated initiative intended to reduce children's exposure to CT radiation was started by pediatric radiologists in 2005. The initiative addressed multiple issues including eliminating multiphase studies, decreasing inappropriate scans, educating referring providers, training residents and technologists, replacing CT with ultrasound or MRI, and ensuring availability of pediatric radiologists for consultation. During the study period, the total number of CT scans decreased by 24 %. When accounting for the number of scans per visit to the emergency department (ED), the numbers of abdominal and head CT scans decreased by 37.2 and 35.2 %, respectively. For abdominal scans, the average number of phases per scan decreased from 1.70 to 1.04. Upon surveying the pediatric ED staff, it was revealed that the most influential factors on ordering of scans were daily communication with pediatric radiologists, followed by journal articles and lectures by pediatric radiologists. We concluded that a non pediatric-focused facility can achieve dramatic reduction in CT radiation exposure to children; however, this is most effectively achieved through a dedicated, multidisciplinary process led by pediatric radiologists. PMID- 26263879 TI - Seymour Sarason Remembered: "Plus ca change...", "Psychology Misdirected", and "Community Psychology and the Anarchist Insight". AB - The intellectual legacy of Seymour Sarason continues to serve as a critical resource for the field of community psychology. The present paper draws on one of Sarason's favorite aphorisms and two of his seminal writings to suggest the relevance of ideas articulated 35-40 years ago for the current time. Each in their own way highlights the importance of unearthing and interrogating core assumptions underlying our research and our efforts to make a positive difference. The aphorism reminds us that the rhetoric of change is far easier to articulate than to enact and all too often ignores or disguises issues of power among actors. The "misdirection" of Psychology reflected his assertion that the asocial, acultural, and ahistorical nature of American Psychology reflected American culture more generally and ill prepared it to understand and engage in social change, particularly with respect to educational reform. The "anarchist insight" articulated his belief in interrogating the implications of the increasingly interdependent relationship of science and the state for the autonomy of scientists and scientific inquiry. The evidence-based practice movement is offered as an example of the current day relevance of the aphorism and core insights of these two papers. The paper concludes with a plea to rekindle the discussion and continued examination of Sarason's paradigmatic insights for the intellectual and social development of the field. PMID- 26263880 TI - Relativistic electron avalanches as a thunderstorm discharge competing with lightning. AB - Gamma-ray 'glows' are long duration (seconds to tens of minutes) X-ray and gamma ray emission coming from thunderclouds. Measurements suggest the presence of relativistic runaway electron avalanches (RREA), the same process underlying terrestrial gamma-ray flashes. Here we demonstrate that glows are relatively a common phenomena near the tops of thunderstorms, when compared with events such as terrestrial gamma-ray flashes. Examining the strongest glow measured by the airborne detector for energetic emissions, we show that this glow is measured near the end of a downward RREA, consistent with occurring between the upper positive charge layer and the negative screening layer above it. The glow discharges the upper positive layer by >=9.6 mA, strong enough to be an important charging mechanism of the storm. For this glow, the gamma-ray flux observed is close to the value at which relativistic feedback processes become important, with an avalanche multiplication factor of 4,500. PMID- 26263881 TI - Rhus coriaria induces senescence and autophagic cell death in breast cancer cells through a mechanism involving p38 and ERK1/2 activation. AB - Here, we investigated the anticancer effect of Rhus coriaria on three breast cancer cell lines. We demonstrated that Rhus coriaria ethanolic extract (RCE) inhibits the proliferation of these cell lines in a time- and concentration dependent manner. RCE induced senescence and cell cycle arrest at G1 phase. These changes were concomitant with upregulation of p21, downregulation of cyclin D1, p27, PCNA, c-myc, phospho-RB and expression of senescence-associated beta galactosidase activity. No proliferative recovery was detected after RCE removal. Annexin V staining and PARP cleavage analysis revealed a minimal induction of apoptosis in MDA-MB-231 cells. Electron microscopy revealed the presence of autophagic vacuoles in RCE-treated cells. Interestingly, blocking autophagy by 3 methyladenine (3-MA) or chloroquine (CQ) reduced RCE-induced cell death and senescence. RCE was also found to activate p38 and ERK1/2 signaling pathways which coincided with induction of autophagy. Furthermore, we found that while both autophagy inhibitors abolished p38 phosphorylation, only CQ led to significant decrease in pERK1/2. Finally, RCE induced DNA damage and reduced mutant p53, two events that preceded autophagy. Our findings provide strong evidence that R. coriaria possesses strong anti-breast cancer activity through induction of senescence and autophagic cell death, making it a promising alternative or adjunct therapeutic candidate against breast cancer. PMID- 26263882 TI - Effects of electron acceptors on soluble reactive phosphorus in the overlying water during algal decomposition. AB - Endogenous phosphorus (P) release from sediments is an important factor to cause eutrophication and, hence, algal bloom in lakes in China. Algal decomposition depletes dissolved oxygen (DO) and causes anaerobic conditions and therefore increases P release from sediments. As sediment P release is dependent on the iron (Fe) cycle, electron acceptors (e.g., NO3 (-), SO4 (2-), and Mn(4+)) can be utilized to suppress the reduction of Fe(3+) under anaerobic conditions and, as such, have the potential to impair the release of sediment P. Here, we used a laboratory experiment to test the effects of FeCl3, MnO2, and KNO3 on soluble reactive phosphorus (SRP) concentration and related chemical variables in the overlying water column during algal decomposition at different algal densities. Results showed that algal decomposition significantly depleted DO and thereby increased sediment Fe-bound P release. Compared with the control, addition of FeCl3 significantly decreased water SRP concentration through inhibiting sediment P release. Compared with FeCl3, addition of MnO2 has less potential to suppress sediment P release during algal decomposition. Algal decomposition has the potential for NO3 (-) removal from aquatic ecosystem through denitrification and by that alleviates the suppressing role of NO3 (-) on sediment P release. Our results indicated that FeCl3 and MnO2 could be efficient in reducing sediment P release during algal decomposition, with the strongest effect found for FeCl3; large amounts of NO3 (-) were removed from the aquatic ecosystem through denitrification during algal decomposition. Moreover, the amounts of NO3 (-) removal increased with increasing algal density. PMID- 26263883 TI - A margin of exposure approach to assessment of non-cancerous risk of diethyl phthalate based on human exposure from bottled water consumption. AB - Phthalates may be present in food due to their widespread presence as environmental contaminants or due to migration from food contact materials. Exposure to phthalates is considered to be potentially harmful to human health as well. Therefore, determining the main source of exposure is an important issue. So, the purpose of this study was (1) to measure the release of diethyl phthalate (DEP) in bottled water consumed in common storage conditions specially low temperature and freezing conditions; (2) to evaluate the intake of DEP from polyethylene terephthalate (PET) bottled water and health risk assessment; and (3) to assess the contribution of the bottled water to the DEP intake against the tolerable daily intake (TDI) values. DEP migration was investigated in six brands of PET-bottled water under different storage conditions room temperature, refrigerator temperature, freezing conditions (40 degrees C ,0 degrees C and 18 degrees C) and outdoor] at various time intervals by magnetic solid extraction (MSPE) using gas chromatography-mass spectroscopy (GC-MS). Eventually, a health risk assessment was conducted and the margin of exposure (MOE) was calculated. The results indicate that contact time with packaging and storage temperatures caused DEP to be released into water from PET bottles. But, when comprising the DEP concentration with initial level, the results demonstrated that the release of phthalates were not substantial in all storage conditions especially at low temperatures (<25 degrees C) and freezing conditions. The daily intake of DEP from bottled water was much lower than the reference value. However, the lowest MOE was estimated for high water consumers (preschooler > children > lactating women > teenagers > adults > pregnant women), but in all target groups, the MOE was much higher than 1000, thus, low risk is implied. Consequently, PET-bottled water is not a major source of human exposure to DEP and from this perspective is safe for consumption. PMID- 26263884 TI - Nucleoplasmic bridges and tailed nuclei are signatures of radiation exposure in Oreochromis mossambicus using erythrocyte micronucleus cytome assay (EMNCA). AB - Gamma radiation-induced genetic perturbations in aquatic vertebrates is largely unknown at low-dose rate, especially in the wake of a nuclear disaster and/or other environmental outbreaks. Freshwater fish, Oreochromis mossambicus subjected to low-dose rate (2 mGy/min) at 2.5-, 5-, and 10-Gy doses, were analyzed for "exposure signatures" in blood samples drawn on days 3, 6, 12, 18, and 30, respectively. Significant dose-dependent increments in micronuclei frequency and other anomalies such as nucleoplasmic bridges and tailed nuclei were observed and exhibit a strong positive correlation, suggesting that they could be used as prospective signatures of radiation exposure. Similarly increased incidence of apoptosis and DNA repair machinery circuits at high and low doses were noted. This work highlighted "cytogenetic signatures" in fish and the sensitivity of these endpoints toward low-dose rate of radiation exposure. PMID- 26263885 TI - Inoculating plants with the endophytic bacterium Pseudomonas sp. Ph6-gfp to reduce phenanthrene contamination. AB - Plant organic contamination poses a serious threat to the safety of agricultural products and human health worldwide, and the association of endophytic bacteria with host plants may decrease organic pollutants in planta. In this study, we firstly determined the growth response and biofilm formation of endophytic Pseudomonas sp. Ph6-gfp, and then systematically evaluated the performance of different plant colonization methods (seed soaking (SS), root soaking (RS), leaf painting (LP)) for circumventing the risk of plant phenanthrene (PHE) contamination. After inoculation for 48 h, strain Ph6-gfp grew efficiently with PHE, oxalic acid, or malic acid as the sole sources of carbon and energy. Moreover, strain Ph6-gfp could form robust biofilms in LB medium. In greenhouse hydroponic experiments, strain Ph6-gfp could actively colonize inoculated plants internally, and plants colonized with Ph6-gfp showed a higher capacity for PHE removal. Compared with the Ph6-gfp-free treatment, the accumulations of PHE in Ph6-gfp-colonized plants via SS, RS, and LP were 20.1, 33.1, and 7.1 %, respectively, lower. Our results indicate that inoculating plants with Ph6-gfp could lower the risk of plant PHE contamination. RS was most efficient for improving PHE removal in whole plant bodies by increasing the cell numbers of Ph6 gfp in plant roots. The findings in this study provide an optimized method to strain Ph6-gfp reduce plant PAH residues, which may be applied to agricultural production in PAH-contaminated soil. PMID- 26263886 TI - Thermal desorption of PCB-contaminated soil with sodium hydroxide. AB - The thermal desorption was combined with sodium hydroxide to remediate polychlorinated biphenyl (PCB)-contaminated soil. The experiments were conducted at different temperatures ranging from 300 to 600 degrees C with three NaOH contents of 0.1, 0.5, and 1 %. The results showed that thermal desorption was effective for PCB removal, destruction, and detoxication, and the presence of NaOH enhanced the process by significant dechlorination. After treatment with 0.1 % NaOH, the removal efficiency (RE) increased from 84.8 % at 300 degrees C to 98.0 % at 600 degrees C, corresponding to 72.7 and 91.7 % of destruction efficiency (DE). With 1 % NaOH content treated at 600 degrees C, the RE and DE were 99.0 and 93.6 %, respectively. The effect of NaOH content on PCB removal was significant, especially at lower temperature, yet it weakened under higher temperature. The interaction between NaOH content and temperature influenced the PCB composition. The higher temperature with the help of NaOH effectively increased the RE and DE of 12 dioxin-like PCBs (based on WHO-TEQ). PMID- 26263887 TI - Influence of substrate type on microbial community structure in vertical-flow constructed wetland treating polluted river water. AB - Microorganisms attached on the surfaces of substrate materials in constructed wetland play crucial roles in the removal of organic and inorganic pollutants. However, the impact of substrate material on wetland microbial community structure remains unclear. Moreover, little is known about microbial community in constructed wetland purifying polluted surface water. In this study, Illumina high-throughput sequencing was applied to profile the spatial variation of microbial communities in three pilot-scale surface water constructed wetlands with different substrate materials (sand, zeolite, and gravel). Bacterial community diversity and structure showed remarkable spatial variation in both sand and zeolite wetland systems, but changed slightly in gravel wetland system. Bacterial community was found to be significantly influenced by wetland substrate type. A number of bacterial groups were detected in wetland systems, including Proteobacteria, Chloroflexi, Bacteroidetes, Acidobacteria, Cyanobacteria, Nitrospirae, Planctomycetes, Actinobacteria, Firmicutes, Chlorobi, Spirochaetae, Gemmatimonadetes, Deferribacteres, OP8, WS3, TA06, and OP3, while Proteobacteria (accounting for 29.1-62.3 %), mainly composed of Alpha-, Beta-, Gamma-, and Deltaproteobacteria, showed the dominance and might contribute to the effective reduction of organic pollutants. In addition, Nitrospira-like microorganisms were abundant in surface water constructed wetlands. PMID- 26263888 TI - l-amino acid oxidase from Bothrops marajoensis causes nephrotoxicity in isolated perfused kidney and cytotoxicity in MDCK renal cells. AB - Renal alterations caused by Bothrops venom and its compounds are studied to understand these effects and provide the best treatment. Previously, we studied the renal effect of the whole venom of Bothrops marajoensis and its phospholipase A2 (PLA2), but these effects could not to be attributed to PLA2. To continue the study, we report in this short communication the effects of l-amino acid oxidase from B. marajoensis venom (LAAOBm) on renal function parameter alterations observed in the same model of isolated perfused kidney, as well as the cytotoxic effect on renal cells. LAAOBm caused a decrease in PP, RVR, UF, GFR, %TNa(+) and %TCl(-), very similar to the effects of whole venom using the same model. We also demonstrated its cytotoxicity in MDCK cells with IC50 of 2.5 MUg/mL and late apoptotic involvement demonstrated by flow cytometry assays. In conclusion, we suggested that LAAOBm is a nephrotoxic compound of B. marajoensis venom. PMID- 26263889 TI - Synergistic inflammatory effect of PM10 with mycotoxin deoxynivalenol on human lung epithelial cells. AB - The presence of deoxynivalenol (DON), a mycotoxin produced by Fusarium species, has been reported worldwide in food and feedstuffs. Even though oral intake is the main route of exposure, DON inhalation is also of concern in workers and exposed population. Particulate matter (PM) is one of the most important causes of air quality detriment and it induces several adverse health effects. Therefore it is of primary importance to understand possible combined effects of DON and PM. The alveolar type II, A549, and the bronchial epithelial, BEAS-2B, cell lines were exposed for 24 h to different concentrations of DON (10-1000 ng/ml), PM10 (5 MUg/cm(2), sampled in summer or winter season), and a combination of these pollutants. Cell death, interleukins release and cell cycle alteration were analysed; protein array technique was also applied to evaluate proteins activation related to MAP-kinases cascade. Our results demonstrate that low doses of PM and DON used alone have scarce toxic effects, while induce cytotoxicity and inflammation when used in combination. This observation outlines the importance of investigation on the combined effects of air pollutants for their possible outcomes on human health. PMID- 26263890 TI - Organic alloys of room temperature liquids thiophenol and selenophenol. AB - The first examples of organic alloys of two room temperature liquids, obtained and characterized via in situ cryo-crystallography, are presented. Thiophenol and selenophenol, which exhibit isostructurality and similar modes of S?S and Se?Se homo-chalcogen interactions along with weak and rare S-H?S and Se-H?Se hydrogen bonds, are shown to form solid solutions exhibiting Veggard's law-like trends. PMID- 26263891 TI - Mechanistic Investigations of the Stereoselective Rare Earth Metal-Mediated Ring Opening Polymerization of beta-Butyrolactone. AB - Poly(3-hydroxybutyrate) (PHB) is produced by numerous bacteria as carbon and energy reserve storage material. Whereas nature only produces PHB in its strictly isotactic (R) form, homogeneous catalysis, when starting from racemic (rac) beta butyrolactone (BL) as monomer, can in fact produce a wide variety of tacticities. The variation of the metal center and the surrounding ligand structure enable activity as well as tacticity tuning. However, no homogeneous catalyst exists to date that is easy to modify, highly active, and able to produce PHB with high isotacticities from rac-beta-BL. Therefore, in this work, the reaction kinetics of various 2-methoxyethylamino-bis(phenolate) lanthanide (Ln=Sm, Tb, Y, Lu) catalysts are examined in detail. The order in monomer and catalyst are determined to elucidate the reaction mechanism and the results are correlated with DFT calculations of the catalytic cycle. Furthermore, the enthalpies and entropies of the rate-determining steps are determined through temperature dependent in situ IR measurements. Experimental and computational results converge in one specific mechanism for the ring-opening polymerization of BL and even allow us to rationalize the preference for syndiotactic PHB. PMID- 26263892 TI - Developing immunological methods for detecting Macrobrachium rosenbergii nodavirus and extra small virus using a recombinant protein preparation. AB - Macrobrachium rosenbergii nodavirus (MrNV) and extra small virus (XSV) have been identified as the causative agents for white tail disease (WTD) of M. rosenbergii. In this study, the gene sequences encoding MrNV and XSV capsid proteins were separately ligated into the pGEX-4T-3 expression vector and transformed into Escherichia coli. After induction, glutathione-S-transferase (GST)-tagged MrNV and XSV fusion proteins were obtained with molecular masses of 68 and 43 kDa, respectively. Specific polyclonal antibodies for MrNV and XSV against viral recombinant proteins and infected prawn tissues were verified using Western blotting. According to immunodot blot assay results, the detection sensitivities of antibodies were approximately 5 ng MUL(-1) for both recombinant proteins GST-MrNV and GST-XSV. In additional, MrNV and XSV were detected at dilution levels of 1:2560 and 1:640 in the infected prawn tissues, respectively. No cross-reactions with white spot syndrome virus or grouper nervous necrosis virus were observed using immunodot blot assays. MrNV and XSV in infected muscle tissues were detected using immunohistochemistry. Although the detection limit of the immunodot blot assay was lower than that of nested reverse transcription polymerase chain reaction, these polyclonal antibodies can be useful for confirming MrNV and XSV infections in field tests. PMID- 26263893 TI - Estimating sign-dependent societal preferences for quality of life. AB - This paper is the first to apply prospect theory to societal health-related decision making. In particular, we allow for utility curvature, equity weighting, sign-dependence, and loss aversion in choices concerning quality of life of other people. We find substantial inequity aversion, both for gains and losses, which can be attributed to both diminishing marginal utility and differential weighting of better-off and worse-off. There are also clear framing effects, which violate expected utility. Moreover, we observe loss aversion, indicating that subjects give more weight to one group's loss than another group's gain of the same absolute magnitude. We also elicited some information on the effect of the age of the studied group. The amount of inequity aversion is to some extent influenced by the age of the considered patients. In particular, more inequity aversion is observed for gains of older people than gains of younger people. PMID- 26263894 TI - Long-term outcome of laparoscopic Nissen-Rossetti fundoplication versus Thal fundoplication in children with esophageal hiatal hernia: a retrospective report from two children's medical centers in Shanghai. AB - BACKGROUND: This study was undertaken to investigate the intraoperative and postoperative complications, efficacy and outcome of two laparoscopic fundoplications for the treatment of esophageal hiatal hernia in children. METHODS: To find a rational procedure, we performed a retrospective analysis of 136 children with esophageal hiatal hernia who underwent laparoscopic Nissen Rossetti or Thal fundoplication at two children's hospitals in Shanghai over 13 years. The median follow-up time of the children was 42 months (range: 1-138 months). Their age varied from 1 month to 11 years (median: 18.6 months). RESULTS: All the children underwent laparoscopic fundoplications (72 cases of Nissen-Rossetti and 60 cases of Thal fundoplication) and 4 children converted to open surgery. The mean age of the children at the time of operation was 1.6+/-1.9 years, and the mean weight was 9.1+/-5.6 kg. Gastroesophageal reflux was significantly more severe after a Thal fundoplication (P=0.003) and slight esophageal stenosis was significant after a Nissen-Rossetti fundoplication (P=0.02). The recurrent rate of hiatal hernia was 2.8% (2/72) after Nissen Rossetti fundoplication in contrast to 5% (3/60) after Thal fundoplication. No death occurred after surgery. CONCLUSION: There was no statistical difference of recurrence between laparoscopic Nissen-Rossetti and Thal fundoplication in the long-term outcomes. The rate of slight dysphagia was higher in the Nissen Rossetti group. The Thal group had a significantly higher recurrence rate of gastroesophageal reflux. There still exited learning curve for this procedure. The incidence rate of complications is significantly related to the proficiency of pediatric surgeon. PMID- 26263895 TI - New insights into the molecular mechanism of the Rab GTPase Sec4p activation. AB - BACKGROUND: Sec4p is a small monomeric Ras-related GTP-binding protein (23 kDa) that regulates polarized exocytosis in S. cerevisiae. In this study we examine the structural effects of a conserved serine residue in the P-loop corresponding to G12 in Ras. RESULTS: We show that the Sec4p residue serine 29 forms a hydrogen bond with the nucleotide. Mutations of this residue have a different impact than equivalent mutations in Ras and can form stable associations with the exchange factor allowing us to elucidate the structure of a complex of Sec4p bound to the exchange factor Sec2p representing an early stage of the exchange reaction. CONCLUSIONS: Our structural investigation of the Sec4p-Sec2p complex reveals the role of the Sec2p coiled-coil domain in facilitating the fast kinetics of the exchange reaction. For Ras-family GTPases, single point mutations that impact the signaling state of the molecule have been well described however less structural information is available for equivalent mutations in the case of Rab proteins. Understanding the structural properties of mutants such as the one described here, provides useful insights into unique aspects of Rab GTPase function. PMID- 26263896 TI - Description of vertebral and liver alveolar echinococcosis cases in Cynomolgus monkeys (Macaca fascicularis). AB - BACKGROUND: Echinococcus multilocularis, the causative agent of alveolar echinococcosis, is a fox tapeworm widely distributed in Europe with an increase of endemic area in recent years. Many mammal species including humans and non human primates can be infected by accidental ingestion of eggs. CASE PRESENTATION: In March 2011, a 5-year-old zoo-raised male cynomolgus macaque (Macaca fascicularis) presented a paresis of the lower limbs which evolved into paralysis. Lesions in liver and vertebra were observed on tomography scan. E. multilocularis infection was diagnosed post-mortem by morphological and histological examination and detection of Em DNA by polymerase chain reaction. Serodiagnosis of other primates of the colony using enzyme-linked immunosorbent assay (ELISA) was negative. In June 2013, at necroscopy, a hepatic and a paravertebral masses were detected in a second cynomolgus macaque of the same colony. Serology and DNA isolated from hepatic and abdominal cysts confirmed E. multilocularis infection. CONCLUSIONS: We described hear vertebral and liver localization of alveolar echinococcosis in non-human primates. The animals lived in an indoor/outdoor housing facility, where the probable mode of contamination is by ingestion of food foraging around the enclosure which could be contaminated with fox feces. Serological survey in the facility should allow us to estimate the risk of human contamination and the zoonotic risk of monkey infection due to environmental contamination. PMID- 26263897 TI - Genetic architecture of cyst nematode resistance revealed by genome-wide association study in soybean. AB - BACKGROUND: Bi-parental mapping populations have been commonly utilized to identify and characterize quantitative trait loci (QTL) controlling resistance to soybean cyst nematode (SCN, Heterodera glycines Ichinohe). Although this approach successfully mapped a large number of SCN resistance QTL, it captures only limited allelic diversity that exists in parental lines, and it also has limitations for genomic resolution. In this study, a genome-wide association study (GWAS) was performed using a diverse set of 553 soybean plant introductions (PIs) belonging to maturity groups from III to V to detect QTL/genes associated with SCN resistance to HG Type 0. RESULTS: Over 45,000 single nucleotide polymorphism (SNP) markers generated by the SoySNP50K iSelect BeadChip (http// www.soybase.org ) were utilized for analysis. GWAS identified 14 loci distributed over different chromosomes comprising 60 SNPs significantly associated with SCN resistance. Results also confirmed six QTL that were previously mapped using bi parental populations, including the rhg1 and Rhg4 loci. GWAS identified eight novel QTL, including QTL on chromosome 10, which we have previously mapped by using a bi-parental population. In addition to the known loci for four simple traits, such as seed coat color, flower color, pubescence color, and stem growth habit, two traits, like lodging and pod shattering, having moderately complex inheritance have been confirmed with great precision by GWAS. CONCLUSIONS: The study showed that GWAS can be employed as an effective strategy for identifying complex traits in soybean and for narrowing GWAS-defined genomic regions, which facilitates positional cloning of the causal gene(s). PMID- 26263898 TI - Reliability and validity of a new HIV-specific questionnaire with adults living with HIV in Canada and Ireland: the HIV Disability Questionnaire (HDQ). AB - BACKGROUND: Our aim was to assess internal consistency reliability, construct validity, and test-retest reliability of the HDQ with adults living with HIV in Canada and Ireland. METHODS: We recruited adults 18 years of age or older living with HIV from hospital clinics and AIDS service organizations in Canada and Ireland. We administered the HDQ paired with reference measures (World Health Organization Disability Assessment Schedule, SF-36 Questionnaire, Medical Outcomes Study Social Support Survey), and a demographic questionnaire. We calculated HDQ disability presence, severity and episodic scores (scored from 0 100). We calculated Cronbach's alpha and Intraclass Correlation Coefficients (ICC) (Canada only) for the disability severity and episodic scores and considered coefficients >0.80 and >0.70 as acceptable, respectively. To assess construct validity, we tested 40 a priori hypotheses of correlations between scores on the HDQ and reference measures and two known group hypotheses comparing HDQ presence and severity scores based on age and comorbidity. We considered acceptance of at least 75% of hypotheses as demonstrating support for construct validity. RESULTS: Of the 235 participants (139 Canada; 96 Ireland), the majority were men (74% Ireland; 82% Canada) and were taking antiretroviral therapy (88% Ireland; 91% Canada). Compared with Irish participants, Canadian participants were older (median age: 48 versus 41 years) and reported living with a higher median number of comorbidities (4 versus 1). Cronbach's alpha for Irish and Canadian participants were 0.97 (95% confidence interval (CI): 0.97-0.98) and 0.96 (95 % CI: 0.95-0.98), respectively, for the severity scale and 0.98 (95 % CI: 0.97-0.98) and 0.96 (95 % CI: 0.95-0.98), respectively, for the episodic scale. Of the 40 construct validity correlation hypotheses, 32 (80%) and 22 (55%) were supported among the Canadian and Irish samples respectively; both (100%) known group hypotheses were also supported. ICC values for Canadian participants ranged from 0.80 (95 % CI: 0.71, 0.86) in the cognitive domain to 0.89 (95 % CI: 0.83, 0.92) in the social inclusion domain. CONCLUSIONS: The HDQ demonstrates internal consistency reliability and a variable degree of construct validity when administered to adults living with HIV in Canada and Ireland. The HDQ demonstrates test-retest reliability when administered to adults with HIV in Canada. Further validation of the HDQ outside of Canada is needed. PMID- 26263899 TI - Metrics for evaluating 3D medical image segmentation: analysis, selection, and tool. AB - BACKGROUND: Medical Image segmentation is an important image processing step. Comparing images to evaluate the quality of segmentation is an essential part of measuring progress in this research area. Some of the challenges in evaluating medical segmentation are: metric selection, the use in the literature of multiple definitions for certain metrics, inefficiency of the metric calculation implementations leading to difficulties with large volumes, and lack of support for fuzzy segmentation by existing metrics. RESULT: First we present an overview of 20 evaluation metrics selected based on a comprehensive literature review. For fuzzy segmentation, which shows the level of membership of each voxel to multiple classes, fuzzy definitions of all metrics are provided. We present a discussion about metric properties to provide a guide for selecting evaluation metrics. Finally, we propose an efficient evaluation tool implementing the 20 selected metrics. The tool is optimized to perform efficiently in terms of speed and required memory, also if the image size is extremely large as in the case of whole body MRI or CT volume segmentation. An implementation of this tool is available as an open source project. CONCLUSION: We propose an efficient evaluation tool for 3D medical image segmentation using 20 evaluation metrics and provide guidelines for selecting a subset of these metrics that is suitable for the data and the segmentation task. PMID- 26263901 TI - Diagnostic value of (18)F-FDG PET/CT as first choice in the detection of recurrent colorectal cancer due to rising CEA. AB - BACKGROUND: The diagnostic value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) as the first imaging approach in the evaluation of rising carcinoembryonic antigen (CEA) is not clear. The objective of this study was to investigate the value of (18)F-FDG PET/CT in patients with colorectal cancer (CRC) and suspected recurrence based on rising CEA. METHODS: A total of 73 patients with CRC were referred to PET/CT after radical surgery. Generally, all patients were scheduled to follow a CT-based post surgical follow-up regimen. In the case of rising CEA, (18)F-FDG PET/CT was performed in most patients with contrast-enhanced CT. The PET/CT images were independently reviewed by two readers. The presence or absence of recurrence was based on histology and/or standardized clinical follow-up. RESULTS: Among 35 patients who had confirmed recurrence of CRC, PET/CT demonstrated recurrence with a sensitivity of 85.7 %, a specificity of 94.7 %, a positive predictive value of 93.8 %, and a negative predictive value of 87.8 %. The SUVmax ranged from 1.3 to 19.9. The mean time since the last postoperative imaging and PET/CT was 8 months (median 4 months). CEA values at referral ranged from 1.5 to 164.0 MUg/L (median 5.6 MUg/L). The diagnostic properties of PET/CT were analyzed in subgroups of patients with a single rising CEA sample (30 patients, 41 %), 31 patients (43 %) with two or more consecutive increases, and 12 patients (16 %) with persistently elevated values. CONCLUSIONS: (18)F-FDG PET/contrast-enhanced CT has high diagnostic accuracy in the diagnosis of recurrent CRC, even in patients in a conventional CT-based follow-up program. PMID- 26263900 TI - An evaluation of variation in published estimates of schizophrenia prevalence from 1990?2013: a systematic literature review. AB - BACKGROUND: There is a lack of consistency in findings across studies on the prevalence of schizophrenia, and no recent systematic review of the literature exists. The purpose of this study is to provide an updated systematic review of population-based prevalence estimates and to understand the factors that could account for this variation in prevalence estimates. METHODS: MEDLINE, Embase, and PsycInfo databases were searched for observational studies describing schizophrenia prevalence in general populations from 2003-2013 and supplemented by studies from a prior review covering 1990-2002. Studies reporting prevalence estimates from specialized populations such as institutionalized, homeless, or incarcerated persons were excluded. Prevalence estimates were compared both across and within studies by factors that might contribute to variability using descriptive statistics. RESULTS: Sixty-five primary studies were included; thirty one (48 %) were from Europe and 35 (54 %) were conducted in samples of >=50,000 persons. Among 21 studies reporting 12-month prevalence, the median estimate was 0.33 % with an interquartile range (IQR) of 0.26 %-0.51 %. The median estimate of lifetime prevalence among 29 studies was 0.48 % (IQR: 0.34 %-0.85 %). Prevalence across studies appeared to vary by study design, geographic region, time of assessment, and study quality scores; associations between study sample size and prevalence were not observed. Within studies, age-adjusted estimates were higher than crude estimates by 17 %-138 %, the use of a broader definition of schizophrenia spectrum disorders compared to schizophrenia increased case identification by 18 %-90 %, identification of cases from inpatient-only settings versus any setting decreased prevalence by 60 %, and no consistent trends were noted by differing diagnostic criteria. CONCLUSIONS: This review provides updated information on the epidemiology of schizophrenia in general populations, which is vital information for many stakeholders. Study characteristics appear to play an important role in the variation between estimates. Overall, the evidence is still sparse; for many countries no new studies were identified. PMID- 26263902 TI - Development and analysis of a 20K SNP array for potato (Solanum tuberosum): an insight into the breeding history. AB - KEY MESSAGE: A 20K SNP array was developed and a comprehensive set of tetraploid cultivar was genotyped. This allowed us to identify footprints of the breeding history in contemporary breeding material such as identification of introgression segments, selection and founder signatures. A non-redundant subset of 15,138 previously identified SNPs and 4454 SNPs originating from the SolCAP project were combined into a 20k Infinium SNP array for genotyping a total of 569 potato genotypes. In this study we describe how this SNP array (encoded SolSTW array) was designed and analysed with fitTetra, software designed for autotetraploids. Genotypes from different countries and market segments, complemented with historic cultivars and important progenitors, were genotyped. This comprehensive set of genotypes combined with the deliberate inclusion of a large proportion of SNPs with a low minor allele frequency allowed us to distinguish genetic variation contributed by introgression breeding. This "new" (post 1945) genetic variation is located on specific chromosomal regions and enables the identification of SNP markers linked to R-genes. In addition, when the genetic composition of modern cultivars was compared with cultivars released before 1945, it appears that 96% of the genetic variants present in those ancestral cultivars remains polymorphic in modern cultivars. Hence, genetic erosion is almost absent in potato. Finally, we studied population genetic processes shaping the genetic composition of the modern European potato including drift, selection and founder effects. This resulted in the identification of major founders contributing to contemporary germplasm. PMID- 26263903 TI - Cost Effectiveness of Monoclonal Antibody Therapy for Rare Diseases: A Systematic Review. AB - BACKGROUND: Monoclonal antibody (mAb)-based orphan drugs have led to advances in the treatment of diseases by selectively targeting molecule functions. However, their high treatment costs impose a substantial cost burden on patients and society. OBJECTIVES: The study aimed to systematically review cost-effectiveness evidence of mAb orphan drugs. METHODS: Ovid MEDLINE((r)), EMBASE((r)), and PsycINFO((r)) were searched in June 2014 and articles were selected if they conducted economic evaluations of the mAb orphan drugs that had received marketing approval in the USA. The quality of the selected studies was assessed using the Quality of Health Economic Studies (QHES) instrument. RESULTS: We reviewed 16 articles that included 24 economic evaluations of nine mAb orphan drugs. Six of these nine drugs were included in cost-utility analysis studies, whereas three drugs were included in cost-effectiveness analysis studies. Previous cost-utility analysis studies revealed that four mAb orphan drugs (cetuximab, ipilimumab, rituximab, and trastuzumab) were found to be cost effective; one drug (bevacizumab) was not cost effective; and one drug (infliximab) was not consistent across the studies. Prior cost-effectiveness analysis studies which included three mAb orphan drugs (adalimumab, alemtuzumab, and basiliximab) showed that the incremental cost per effectiveness gained for these drugs ranged from $US4669 to $Can52,536 Canadian dollars. The quality of the included studies was good or fair with the exception of one study. CONCLUSIONS: Some mAb orphan drugs were reported as cost effective under the current decision-making processes. Use of these expensive drugs, however, can raise an equity issue which concerns fairness in access to treatment. The issue of equal access to drugs needs to be considered alongside other societal values in making the final health policy decisions. PMID- 26263905 TI - On the validity of the (13) C-acetate breath test for comparing gastric emptying of different liquid test meals: a validation study using magnetic resonance imaging. AB - BACKGROUND: (13) C-acetate breath testing (BT) is applied to assess and compare gastric emptying of liquid meals. Gastric half-emptying times (t50 ) from BT show offsets compared to t50 values from gamma-scintigraphy and ultrasonography. Linear transformations have been proposed to correct these offsets. This investigation critically validates the BT for the assessment of liquid gastric emptying by using simultaneously recorded meal and total gastric content volume emptying data from magnetic resonance imaging (MRI). METHODS: Data were collected during a recently published double-blind, randomized, cross-over MRI gastric emptying study of three (13) C-labeled enteral formulas differing in protein sources (PMID: 24699556). Breath testing-derived t50 was computed with the analysis methods commonly applied in gastric emptying research, i.e., the exponential-beta function and the Wagner-Nelson (WN) method, respectively. KEY RESULTS: Breath testing t50 values from exponential-beta function and WN method showed a positive and negative offset to MRI data, respectively. Linear regression detected low concordance between MRI and both BT methods revealing meal specific and emptying rate-dependent offsets. The WN method showed worse agreement and correlation with MRI emptying data. Breath testing rather reflected meal volume than total gastric content volume emptying. CONCLUSIONS & INFERENCES: This validation study indicates that the (13) C-acetate breath test may not be applied to compare gastric emptying of arbitrary liquid meals without prior validation by imaging methods. t50 values from BT are biased by (i) the properties of the meal and (ii) the selected method used for (13) CO2 exhalation analysis. No linear transformation common for all meals was applicable to correct the offsets between BT and MRI. PMID- 26263906 TI - Differences in Dynamics between Crosslinked and Non-Crosslinked Hyaluronates Measured by using Fast Field-Cycling Relaxometry. AB - The dynamic properties of water molecules in gels containing linear and crosslinked hyaluronic acid polymers are investigated by using an integrated approach that includes relaxometry, solid-state NMR spectroscopy, and scanning electron microscopy. A model-free analysis of field-dependent nuclear relaxation is applied to obtain information on mobility and the population of different pools of water molecules in the gels. Differences between linear and crosslinked hyaluronic acid polymers are observed, indicating that crosslinking increases both the fraction and the correlation time of water molecules with slow dynamics. PMID- 26263904 TI - Invaders, natives and their enemies: distribution patterns of amphipods and their microsporidian parasites in the Ruhr Metropolis, Germany. AB - BACKGROUND: The amphipod and microsporidian diversity in freshwaters of a heterogeneous urban region in Germany was assessed. Indigenous and non-indigenous host species provide an ideal framework to test general hypotheses on potentially new host-parasite interactions, parasite spillback and spillover in recently invaded urban freshwater communities. METHODS: Amphipods were sampled in 17 smaller and larger streams belonging to catchments of the four major rivers in the Ruhr Metropolis (Emscher, Lippe, Ruhr, Rhine), including sites invaded and not invaded by non-indigenous amphipods. Species were identified morphologically (hosts only) and via DNA barcoding (hosts and parasites). Prevalence was obtained by newly designed parasite-specific PCR assays. RESULTS: Three indigenous and five non-indigenous amphipod species were detected. Gammarus pulex was further distinguished into three clades (C, D and E) and G. fossarum more precisely identified as type B. Ten microsporidian lineages were detected, including two new isolates (designated as Microsporidium sp. nov. RR1 and RR2). All microsporidians occurred in at least two different host clades or species. Seven genetically distinct microsporidians were present in non-invaded populations, six of those were also found in invaded assemblages. Only Cucumispora dikerogammari and Dictyocoela berillonum can be unambiguously considered as non-indigenous co introduced parasites. Both were rare and were not observed in indigenous hosts. Overall, microsporidian prevalence ranged from 50% (in G. roeselii and G. pulex C) to 73% (G. fossarum) in indigenous and from 10% (Dikerogammarus villosus) to 100 % (Echinogammarus trichiatus) in non-indigenous amphipods. The most common microsporidians belonged to the Dictyocoela duebenum- /D. muelleri- complex, found in both indigenous and non-indigenous hosts. Some haplotype clades were inclusive for a certain host lineage. CONCLUSIONS: The Ruhr Metropolis harbours a high diversity of indigenous and non-indigenous amphipod and microsporidian species, and we found indications for an exchange of parasites between indigenous and non-indigenous hosts. No introduced microsporidians were found in indigenous hosts and prevalence of indigenous parasites in non-indigenous hosts was generally low. Therefore, no indication for parasite spillover or spillback was found. We conclude that non-indigenous microsporidians constitute only a minimal threat to the native amphipod fauna. However, this might change e.g. if C. dikerogammari adapts to indigenous amphipod species or if other hosts and parasites invade. PMID- 26263907 TI - Sudden Death by Occult Metastatic Carcinoma. AB - A 33-year-old female collapsed and died suddenly after presenting with acute dyspnea and increasing cough over the preceding several months. Autopsy revealed poorly differentiated linitis plastica adenocarcinoma of the stomach. Microscopic examination of the lungs showed features consistent with pulmonary tumor thrombotic microangiopathy (PTTM). PTTM is a well-described complication in patients with adenocarcinoma. The typical presentation involves acute pulmonary hypertension, right-sided heart failure, and sudden death, often before the adenocarcinoma is discovered. The pathophysiology of PTTM remains elusive; it has been suggested that carcinoma cells may produce substances that influence pulmonary vasculature. Our patient had classic clinical and histologic features of PTTM in addition to prominent extravascular compression by intralymphatic tumor cells. These features undoubtedly caused her precipitous decline and lethal pulmonary hypertension, induced by underlying adenocarcinoma. This case demonstrates that sudden death can occur from pulmonary hypertension induced by metastatic carcinoma with remarkably little prior symptomatology. PMID- 26263908 TI - Ischaemic conditioning reduces kidney injury in an experimental large-animal model of warm renal ischaemia. AB - BACKGROUND: Ischaemic conditioning, using short repeated sequences of intermittent ischaemia, is a strategy that may ameliorate ischaemia-reperfusion injury. The aim of the study was to assess the effects of direct and remote ischaemic conditioning in a porcine model of renal warm ischaemia-reperfusion injury. METHODS: Pigs (50 kg) underwent laparotomy and 60-min occlusion of the left renal pedicle followed by right nephrectomy. Animals were divided into three groups: untreated controls (n = 8); direct postconditioning involving six 15-s cycles of clamping then releasing of the left renal artery (n = 7); or remote periconditioning involving four 5-min cycles of clamping then releasing of the left common iliac artery (n = 8). After 7 days kidney tissue was harvested, and blood and urine samples were collected on postoperative days 1, 3 and 7. RESULTS: The direct postconditioning group had a lower area under the serum creatinine curve (mean(s.d.) 1378(157) versus 2001(1022) umol/l . day respectively; P = 0.036) and peak creatinine level (316(46) versus 501(253) umol/l respectively; P = 0.033) compared with values in control animals. There was a significant increase in serum levels of tumour necrosis factor alpha on day 1 in control animals but not in the conditioning groups (P = 0.013). Urinary levels of neutrophil gelatinase-associated lipocalin increased over the study period in both the control and remote groups (P = 0.001 for both), but not in the direct group (P = 0.176). There was no mortality and no complications related to either conditioning technique. CONCLUSION: In this in vivo large-animal model, direct renal artery ischaemic postconditioning protected kidneys against warm ischaemia injury. This straightforward technique could readily be translated into clinical practice. Surgical relevance Ischaemic conditioning has been shown to improve outcomes in both experimental studies and clinical trials in cardiac surgery. Evidence from small-animal and human studies assessing ischaemic conditioning techniques in renal transplantation have not yet established the optimal technique and timing of conditioning. In this study, a large-animal model of renal warm ischaemia was used to compare different conditioning techniques. Postconditioning applied directly to the renal artery was shown to reduce renal injury. Furthermore, new evidence is provided that shorter cycles of ischaemic postconditioning than previously described can protect against renal injury. Evidence from a large-animal model is provided for different conditioning techniques. The beneficial postconditioning technique described is straightforward to perform and provides an alternative method of conditioning following renal transplantation, with potential for application in clinical practice. PMID- 26263909 TI - Nanobiotechnology Perspectives on Prevention and Treatment of Ortho-paedic Implant Associated Infection. AB - Implants are an inevitable part of orthopaedic surgery. However, implant associated infection remains a major challenge for orthopaedic surgeons and researchers. This review focuses on current options available for prevention of implant associated infection, their drawbacks and future promising applications of nanotechnology-based approaches. Nanobiotechnology has shown remarkable progress in recent years especially in biomaterials, diagnostics, and drug delivery system. Although several applications of nanobiotechnology in orthopaedics have been described, few have elaborated their role in the prevention of implant related infection in orthopaedics. Novel "smart" drug delivery systems that release antibiotics locally in response to stimuli such as pH, temperature, enzymes or antigens; implant surface modification on a nanoscale to inhibit bacterial adhesion and propagation at the surgical site and biological approaches such as gene therapy to neutralize bacterial virulence and biomolecules to inhibit the quorum sensing adhesion of bacteria and disruption of biofilms can be used effectively to prevent orthopaedic implant related bacterial infection. PMID- 26263910 TI - Intrinsic Resistance to Cixutumumab Is Conferred by Distinct Isoforms of the Insulin Receptor. AB - Despite a recent shift away from anti-insulin-like growth factor I receptor (IGF IR) therapy, this target has been identified as a key player in the resistance mechanisms to various conventional and targeted agents, emphasizing its value as a therapy, provided that it is used in the right patient population. Molecular markers predictive of antitumor activity of IGF-IR inhibitors remain largely unidentified. The aim of this study is to evaluate the impact of insulin receptor (IR) isoforms on the antitumor efficacy of cixutumumab, a humanized mAb against IGF-IR, and to correlate their expression with therapeutic outcome. The data demonstrate that expression of total IR rather than individual IR isoforms inversely correlates with single-agent cixutumumab efficacy in pediatric solid tumor models in vivo. Total IR, IR-A, and IR-B expression adversely affects the outcome of cixutumumab in combination with chemotherapy in patient-derived xenograft models of lung adenocarcinoma. IR-A overexpression in tumor cells confers complete resistance to cixutumumab in vitro and in vivo, whereas IR-B results in a partial resistance. Resistance in IR-B-overexpressing cells is fully reversed by anti-IGF-II antibodies, suggesting that IGF-II is a driver of cixutumumab resistance in this setting. The present study links IR isoforms, IGF II, and cixutumumab efficacy mechanistically and identifies total IR as a biomarker predictive of intrinsic resistance to anti-IGF-IR antibody. IMPLICATIONS: This study identifies total IR as a biomarker predictive of primary resistance to IGF-IR antibodies and provides a rationale for new clinical trials enriched for patients whose tumors display low IR expression. PMID- 26263911 TI - Effects of body mass index (BMI) on surgical outcomes: a nationwide survey using a Japanese web-based database. AB - PURPOSE: To define the effects of body mass index (BMI) on operative outcomes for both gastroenterological and cardiovascular surgery, using the National Clinical Database (NCD) of the Japanese nationwide web-based database. METHODS: The subjects of this study were 288,418 patients who underwent typical surgical procedures between January 2011 and December 2012. There were eight gastroenterological procedures, including esophagectomy, distal gastrectomy, total gastrectomy, right hemicolectomy, low anterior resection, hepatectomy of >1 segment excluding the lateral segment, pancreaticoduodenectomy, and surgery for acute diffuse peritonitis (n = 232,199); and five cardiovascular procedures, including aortic valve replacement, total arch replacement (TAR), descending thoracic aorta replacement (descending TAR), and on- or off-pump coronary artery bypass grafting (n = 56,219). The relationships of BMI with operation time and operative mortality for each procedure were investigated, using the NCD. RESULTS: Operation times were longer for patients with a higher BMI. When a BMI cut-off of 30 was used, the operation time for obese patients was significantly longer than that for non-obese patients, for all procedures except esophagectomy (P < 0.01). The mortality rate based on BMI revealed a U-shaped distribution, with both underweight and obese patients having high mortality rates for almost all procedures. CONCLUSIONS: This Japanese nationwide study provides solid evidence to reinforce that both obesity and excessively low weight are factors that impact operative outcomes significantly. PMID- 26263914 TI - Dangers of over-the-counter nitrofurantoin for urinary tract infection. PMID- 26263915 TI - High-level Multi-Resistant and Virulent Escherichia coli in Abeokuta, Nigeria. AB - Multi-resistant Escherichia coli (E. coli) strains co-harboring virulence genes is a cause of high morbidity in Abeokuta, Nigeria. This study was designed to determine some virulent factors among enteropathogenic E. coli in Abeokuta, Nigeria. Approximately non-repetitive 102 isolates of E. coli were recovered from clinical samples from two health facilities in Abeokuta. Biotyping using API and antibiotic susceptibility was determined, and eae and flic genes were assayed by PCR. Antibiotic resistance relatedness was performed by DendroUPGMA. Results showed that 48.0% and 52.0 % were intestinal and extra-intestinal E. coli, ampicillin recorded 100% resistance, amoxycilli/clavulanic acid 64.7%, cotrimoxazole 57.8% and 56.8% resistance against cefotaxime, at MIC >16 ug/mL, 100%, 57.8%, and 50% have MIC50 to ampicillin, tetracycline, and ceftazidime, while 74.5% and 48.0% have MIC90 to ampicillin and ceftazidime. Significant rates of 4.9%, 7.8%, and 9.8% flic, eae, and flic/eae genes were found in intestinal isolates, while 2.9%, 2.0%, and 3.9% were found in extra-intestinal (P < 0.05). Two major clades of the resistant isolates reveal significant antibiotic relatedness among intestinal and extra-intestinal isolates, at 54% resistance similarities with very high multi-antibiotic resistance index of 1.0 (MARI). A high rate of undetected virulent E. coli pathotypes with high resistance could trigger unprecedented morbidity and mortality, mostly among children and the elderly. PMID- 26263913 TI - Inhibition of FAAH confers increased stem cell migration via PPARalpha. AB - Regenerative activity in tissues of mesenchymal origin depends on the migratory potential of mesenchymal stem cells (MSCs). The present study focused on inhibitors of the enzyme fatty acid amide hydrolase (FAAH), which catalyzes the degradation of endocannabinoids (anandamide, 2-arachidonoylglycerol) and endocannabinoid-like substances (N-oleoylethanolamine, N-palmitoylethanolamine). Boyden chamber assays, the FAAH inhibitors, URB597 and arachidonoyl serotonin (AA 5HT), were found to increase the migration of human adipose-derived MSCs. LC-MS analyses revealed increased levels of all four aforementioned FAAH substrates in MSCs incubated with either FAAH inhibitor. Following addition to MSCs, all FAAH substrates mimicked the promigratory action of FAAH inhibitors. Promigratory effects of FAAH inhibitors and substrates were causally linked to activation of p42/44 MAPKs, as well as to cytosol-to-nucleus translocation of the transcription factor, PPARalpha. Whereas PPARalpha activation by FAAH inhibitors and substrates became reversed upon inhibition of p42/44 MAPK activation, a blockade of PPARalpha left p42/44 MAPK phosphorylation unaltered. Collectively, these data demonstrate FAAH inhibitors and substrates to cause p42/44 MAPK phosphorylation, which subsequently activates PPARalpha to confer increased migration of MSCs. This novel pathway may be involved in regenerative effects of endocannabinoids whose degradation could be a target of pharmacological intervention by FAAH inhibitors. PMID- 26263912 TI - Potent Synergy between Spirocyclic Pyrrolidinoindolinones and Fluconazole against Candida albicans. AB - A spiroindolinone, (1S,3R,3aR,6aS)-1-benzyl-6'-chloro-5-(4-fluorophenyl)-7' methylspiro[1,2,3a,6a-tetrahydropyrrolo[3,4-c]pyrrole-3,3'-1H-indole]-2',4,6 trione, was previously reported to enhance the antifungal effect of fluconazole against Candida albicans. A diastereomer of this compound was synthesized, along with various analogues. Many of the compounds were shown to enhance the antifungal effect of fluconazole against C. albicans, some with exquisite potency. One spirocyclic piperazine derivative, which we have named synazo-1, was found to enhance the effect of fluconazole with an EC50 value of 300 pM against a susceptible strain of C. albicans and going as low as 2 nM against some resistant strains. Synazo-1 exhibits true synergy with fluconazole, with an FIC index below 0.5 in the strains tested. Synazo-1 exhibited low toxicity in mammalian cells relative to the concentrations required for antifungal synergy. PMID- 26263917 TI - MSF calls for urgent help for war torn Yemen. PMID- 26263916 TI - Findings from a novel approach to publication guideline revision: user road testing of a draft version of SQUIRE 2.0. AB - BACKGROUND: The Standards for Quality Improvement Reporting Excellence (SQUIRE) Guideline was published in 2008 (SQUIRE 1.0) and was the first publication guideline specifically designed to advance the science of healthcare improvement. Advances in the discipline of improvement prompted us to revise it. We adopted a novel approach to the revision by asking end-users to 'road test' a draft version of SQUIRE 2.0. The aim was to determine whether they understood and implemented the guidelines as intended by the developers. METHODS: Forty-four participants were assigned a manuscript section (ie, introduction, methods, results, discussion) and asked to use the draft Guidelines to guide their writing process. They indicated the text that corresponded to each SQUIRE item used and submitted it along with a confidential survey. The survey examined usability of the Guidelines using Likert-scaled questions and participants' interpretation of key concepts in SQUIRE using open-ended questions. On the submitted text, we evaluated concordance between participants' item usage/interpretation and the developers' intended application. For the survey, the Likert-scaled responses were summarised using descriptive statistics and the open-ended questions were analysed by content analysis. RESULTS: Consistent with the SQUIRE Guidelines' recommendation that not every item be included, less than one-third (n=14) of participants applied every item in their section in full. Of the 85 instances when an item was partially used or was omitted, only 7 (8.2%) of these instances were due to participants not understanding the item. Usage of Guideline items was highest for items most similar to standard scientific reporting (ie, 'Specific aim of the improvement' (introduction), 'Description of the improvement' (methods) and 'Implications for further studies' (discussion)) and lowest (<20% of the time) for those unique to healthcare improvement (ie, 'Assessment methods for context factors that contributed to success or failure' and 'Costs and strategic trade-offs'). Items unique to healthcare improvement, specifically 'Evolution of the improvement', 'Context elements that influenced the improvement', 'The logic on which the improvement was based', 'Process and outcome measures', demonstrated poor concordance between participants' interpretation and developers' intended application. CONCLUSIONS: User testing of a draft version of SQUIRE 2.0 revealed which items have poor concordance between developer intent and author usage, which will inform final editing of the Guideline and development of supporting supplementary materials. It also identified the items that require special attention when teaching about scholarly writing in healthcare improvement. PMID- 26263918 TI - Optimization of Protein Extraction and Two-Dimensional Electrophoresis Protocols for Oil Palm Leaf. AB - Oil palm (Elaeis guineensis) is an important economic crop cultivated for its nutritional palm oil. A significant amount of effort has been undertaken to understand oil palm growth and physiology at the molecular level, particularly in genomics and transcriptomics. Recently, proteomics studies have begun to garner interest. However, this effort is impeded by technical challenges. Plant sample preparation for proteomics analysis is plagued with technical challenges due to the presence of polysaccharides, secondary metabolites and other interfering compounds. Although protein extraction methods for plant tissues exist, none work universally on all sample types. Therefore, this study aims to compare and optimize different protein extraction protocols for use with two-dimensional gel electrophoresis of young and mature leaves from the oil palm. Four protein extraction methods were evaluated: phenol-guanidine isothiocyanate, trichloroacetic acid-acetone precipitation, sucrose and trichloroacetic acid acetone-phenol. Of these four protocols, the trichloroacetic acid-acetone-phenol method was found to give the highest resolution and most reproducible gel. The results from this study can be used in sample preparations of oil palm tissue for proteomics work. PMID- 26263919 TI - Does your organization use gender inclusive forms? Nurses' confusion about trans* terminology. AB - AIMS AND OBJECTIVES: To describe nurses confusion around trans* terminology and to provide a lesson in Trans* 101 for readers. BACKGROUND: Of the estimated 9 million persons in the United States of America who are identified as lesbian, gay, bisexual and transgender, about 950,000 (0.2-0.5% of adult population) are identified as trans* (a term that encompasses the spectrum, including transgender, transsexual, trans man, trans woman and other terms). The Institute of Medicine (2011, The health of lesbian, gay, bisexual and transgender people: Building a foundation for better understanding. The National Academies Press, Washington, DC) identified transgender persons as an understudied population with significant need for health research, yet the nursing literature contains little guidance for educating nurses on trans* issues. DESIGN: This is a mixed methods structured interview design with nurse key informants. The scripted interview was based on the Health Care Equality Index, which evaluates patient-centred care to lesbian, gay, bisexual and transgender patients and families. These data were part of a larger research study that explored the current state of lesbian, gay, bisexual and transgender-sensitive nursing practice. METHOD: Undergraduate nursing students recruited and interviewed 268 nurse key informants about gender inclusive forms (capable of identifying trans* patients) at their agencies. RESULTS: Only 5% reported use of gender inclusive forms, 44% did not know about inclusive forms, 37% did not understand what a gender inclusive form was and 14% confused gender with sexual orientation. CONCLUSION: The study demonstrated a critical need for education in gender identity and sexual orientation terminology. RELEVANCE TO CLINICAL PRACTICE: The lack of understanding of concepts and terminology may affect basic care of lesbian, gay, bisexual and transgender patients especially those who identify as transgender. PMID- 26263920 TI - Construction of a recombinant duck enteritis virus (DEV) expressing hemagglutinin of H5N1 avian influenza virus based on an infectious clone of DEV vaccine strain and evaluation of its efficacy in ducks and chickens. AB - BACKGROUND: Highly pathogenic avian influenza virus (AIV) subtype H5N1 remains a threat to poultry. Duck enteritis virus (DEV)-vectored vaccines expressing AIV H5N1 hemagglutinin (HA) may be viable AIV and DEV vaccine candidates. METHODS: To facilitate the generation and further improvement of DEV-vectored HA(H5) vaccines, we first constructed an infectious clone of DEV Chinese vaccine strain C-KCE (DEV(C-KCE)). Then, we generated a DEV-vectored HA(H5) vaccine (DEV H5(UL55)) based on the bacterial artificial chromosome (BAC) by inserting a synthesized HA(H5) expression cassette with a pMCMV IE promoter and a consensus HA sequence into the noncoding area between UL55 and LORF11. The immunogenicity and protective efficacy of the resulting recombinant vaccine against DEV and AIV H5N1 were evaluated in both ducks and chickens. RESULTS: The successful construction of DEV BAC and DEV-H5(UL55) was verified by restriction fragment length polymorphism analysis. Recovered virus from the BAC or mutants showed similar growth kinetics to their parental viruses. The robust expression of HA in chicken embryo fibroblasts infected with the DEV-vectored vaccine was confirmed by indirect immunofluorescence and western blotting analyses. A single dose of 10(6) TCID50 DEV-vectored vaccine provided 100 % protection against duck viral enteritis in ducks, and the hemagglutination inhibition (HI) antibody titer of AIV H5N1 with a peak of 8.2 log2 was detected in 3-week-old layer chickens. In contrast, only very weak HI titers were observed in ducks immunized with 10(7) TCID50 DEV-vectored vaccine. A mortality rate of 60 % (6/10) was observed in 1 week-old specific pathogen free chickens inoculated with 10(6) TCID50 DEV vectored vaccine. CONCLUSIONS: We demonstrate the following in this study. (i) The constructed BAC is a whole genome clone of DEV(C-KCE). (ii) The insertion of an HA expression cassette sequence into the noncoding area between UL55 and LORF11 of DEV(C-KCE) affects neither the growth kinetics of the virus nor its protection against DEV. (iii) DEV-H5(UL55) can generate a strong humoral immune response in 3-week-old chickens, despite the virulence of this virus observed in 1-week-old chickens. (iv) DEV-H5(UL55) induces a weak HI titer in ducks. An increase in the HI titers induced by DEV-vectored HA(H5) will be required prior to its wide application. PMID- 26263921 TI - A prospective analysis of factors associated with decreased physical activity in patients with cirrhosis undergoing transplant evaluation. AB - BACKGROUND: Physical activity (PA) has been associated with improved recovery time after transplantation. Handgrip strength has been related to post-transplant outcomes. AIM: To evaluate predictors of PA and grip strength in patients with cirrhosis undergoing liver transplant evaluation. METHODS: Single-center, prospective analysis. RESULTS: One hundred patients were evaluated (54% male, mean age 53 +/- 9). Common etiologies of liver disease were non-alcoholic steatohepatitis (27%), hepatitis C (22%) and alcoholic liver disease (21%). Mean model of end-stage liver disease (MELD) score was 13.5. Forty-one percent had a history of smoking. Ninety-three patients completed the International Physical Activity Questionnaire (IPAQ). The median total PA score was 33 metabolic equivalent (MET)-min/wk. The mean total grip strength was 62.1 +/- 22 lb. Total grip strength was found to be an independent predictor of low-moderate PA (OR 4.7, 95% CI 1.4-16.2, p = 0.038), and smoking was the only significant factor associated with reduced grip strength (OR 3.4, 95% CI 1.4-8, p = 0.005). CONCLUSIONS: Patients with end-stage liver disease undergoing liver transplant evaluation have reduced total PA by IPAQ. Total grip strength was found to be a significant predictor of low-moderate PA in patients with cirrhosis. Smoking is a risk factor for reduced grip strength, an important indicator of muscle wasting in cirrhotics. PMID- 26263922 TI - Atypical cutaneous gammadelta T cell proliferation with morphologic features of lymphoma but with clinical features and course of PLEVA or lymphomatoid papulosis. AB - Reactive lymphoid infiltrates of the skin composed predominantly of gamma-delta (gammadelta) T cells are not well described in the literature. Herein we report a case of an otherwise healthy 4-year-old male who presented with a waxing and waning papular rash characterized by small, discrete crusted papules spread across his trunk, face and extremities. Clinical evaluation revealed no evidence of systemic disease. Microscopic examination revealed a dermal, perivascular infiltrate of highly atypical lymphocytes with a gammadelta T cell phenotype, worrisome for primary cutaneous gammadelta T cell lymphoma. The clinical course, however, was that of a reactive condition and prompted consideration of a diagnosis of pityriasis lichenoides et varioliformis acuta (PLEVA) and lymphomatoid papulosis (LyP). In many ways, this case defies current classification schemes and seems to expand the spectrum of reactive gammadelta T cell infiltrates of the skin. PMID- 26263925 TI - Agoraphobia and Melancholia: Thoughts on Milrod's "Emptiness in Agoraphobia Patients". AB - Milrod (2007) identifies persistent emptiness in agoraphobic patients whose symptoms of anxiety and avoidance have remitted. To this important identification, a number of critical considerations may be raised regarding the meanings of emptiness in the psychoanalytic clinic. Milrod's admonishment to distinguish between an emptiness that indicates a deficit in the structure and stability of self-representation, and an emptiness that is strictly defensive, is a case in point. While much of the literature supports an interpretation of emptiness as a defense against overwhelming rage, these patients' assertions and experiences of emptiness can be better explained by the presence of traumatic, unmourned losses. Several explanations are offered as to why agoraphobic patients, in particular, defend unconsciously against mourning. PMID- 26263924 TI - Activation of human naive Th cells increases surface expression of GD3 and induces neoexpression of GD2 that colocalize with TCR clusters. AB - CD4+ T helper lymphocytes (Th) orchestrate the immune response after their activation by antigen-presenting cells. Activation of naive Th cells is reported to generate the reduction in surface epitopes of sialic acid (Sia) in alpha2,3 and alpha2,6 linkages. In this work, we report that in spite of this glycophenotype, anti-CD3/anti-CD28-activated purified human naive Th cells show a significant increase in surface Sia, as assessed by metabolic labeling, compared with resting naive Th cells, suggesting an increased flux of Sia toward Siaalpha2,8 glycoconjugates. To understand this increase as a result of ganglioside up-regulation, we observed that very early after activation, human naive Th cells show an increased expression in surface GD3 and neoexpression of surface GD2 gangliosides, the latter clustering with the T cell receptor (TCR). Also, we report that in contrast to GM2/GD2 synthase null mice, lentiviral vector mediated silencing of the GM2/GD2 synthase in activated human naive Th cells reduced efficient TCR clustering and downstream signaling, as assessed by proliferation assays and IL-2 and IL-2R expression, pointing to an important role of this enzyme in activation of human naive Th cells. PMID- 26263923 TI - Fc glycans of therapeutic antibodies as critical quality attributes. AB - Critical quality attributes (CQA) are physical, chemical, biological or microbiological properties or characteristics that must be within an appropriate limit, range or distribution to ensure the desired product quality, safety and efficacy. For monoclonal antibody therapeutics that rely on fraction crystalizable (Fc)-mediated effector function for their clinical activity, the terminal sugars of Fc glycans have been shown to be critical for safety or efficacy. Different glycosylation variants have also been shown to influence the pharmacodynamic and pharmacokinetic behavior while other Fc glycan structural elements may be involved in adverse immune reactions. This review focuses on the role of Fc glycans as CQAs. Fc glycan information from the published literature is summarized and evaluated for impact on patient safety, immunogenicity, bioactivity and pharmacodynamics/pharmacokinetics. PMID- 26263926 TI - Contextualized Language and Transferential Aspects of Context. AB - The analytic process, in which the patient's and the analyst's internal characters struggle to create a script through the analysand's mouth and the analyst's pen, resembles Pirandello's Six Characters in Search of an Author (1921): different characters come together on the analytic stage to rehearse the analyst's role as coauthor of a play that depicts the ongoing analytic saga. To compose the text for the interplay of characters, the author must search for contexts that may confer meaning upon the words and actions of characters. This involves a search for a mise en scene (stage) that will assign mise en sens (meaning) to the actors' role-specific dialogue. Yet mise en scene, in the theatrical sense, is a set of iconic signs set with its own decor, props, and costumes. In contrast, the psychoanalytic scene is a symbolic stage for the play of words--words that may contain unconscious codes for switching into particular language games. A clinical case report describes a struggle with the contextual analysis of an aspect of a treatment that involved reported episodes of verbal indiscretions "taken out of context" with unwanted consequences. PMID- 26263927 TI - Efficacy of humidity retention bags for the reduced adsorption and improved cleaning of tissue proteins including prion-associated amyloid to surgical stainless steel surfaces. AB - Increasing drying time adversely affects attachment of tissue proteins and prion associated amyloid to surgical stainless steel, and reduces the efficacy of commercial cleaning chemistries. This study tested the efficacy of commercial humidity retention bags to reduce biofouling on surgical stainless steel and to improve subsequent cleaning. Surgical stainless steel surfaces were contaminated with ME7-infected brain homogenates and left to dry for 15 to 1,440 min either in air, in dry polythene bags or within humidity retention bags. Residual contamination pre/post cleaning was analysed using Thioflavin T/SYPRO Ruby dual staining and microscope analysis. An increase in biofouling was observed with increased drying time in air or in sealed dry bags. Humidity retention bags kept both protein and prion-associated amyloid minimal across the drying times both pre- and post-cleaning. Therefore, humidity bags demonstrate a cheap, easy to implement solution to improve surgical instrument reprocessing and to potentially reduce associated hospital acquired infections. PMID- 26263928 TI - Why authors have to use a rigid format for their journal articles. PMID- 26263929 TI - Some rules for writing medical articles for peer-reviewed journals. PMID- 26263930 TI - Inferior epigastric artery pseudoaneurysms. AB - INTRODUCTION: Inferior epigastric artery (IEA) pseudoaneurysms are recognised complications of abdominal wall procedures, and a variety of approaches including surgical excision and ligation, percutaneous procedures and conservative management have been employed in treating this rare complication. METHODS: We describe a case of an IEA pseudoaneurysm diagnosed on computed tomography (CT) angiography, 14 days following a laparoscopic assisted low anterior resection, which was managed successfully with surgical excision and ligation. A review of the literature identified 32 reports of this complication since 1973 with 69% of cases occurring since 2000. FINDINGS: The main aetiology of IEA pseudoaneurysm was abdominal surgery (n=20); 65% of cases were attributable to abdominal wound closure or laparoscopic surgery. Two-thirds (66%) of patients presented between 11 and 63 days, and all except 1 case presented with discomfort, abdominal mass or haemodynamic instability. Colour Doppler ultrasonography was the imaging modality of choice (n=18), either alone or in combination with computed tomography and/or angiography. Surgical ligation and excision and percutaneous coil embolisation formed the mainstay of attempted treatments (69%), particularly following treatment failure using an alternative technique. CONCLUSIONS: The incidence of iatrogenic IEA pseudoaneurysms appears to be increasing. Awareness of this rare complication is of clinical importance to avoid excessive morbidity for affected individuals. PMID- 26263931 TI - Mediastinal parathyroid adenomas and their surgical implications. AB - Primary hyperparathyroidism is a relatively common problem encountered by any endocrine surgical unit. Ectopic parathyroid adenomas have been known to be a common cause of persistent hyperparathyroidism after surgery. A common site of the missed ectopic gland will be that in the mediastinum. However, with the increasing improvement in available imaging, it is likely that this can be diagnosed preoperatively. The surgical approach to the mediastinal parathyroid has also changed vastly over the last decade from maximally invasive to minimally invasive with minimal complications. We provide a review on the entity of mediastinal parathyroid adenomas and their surgical implications. PMID- 26263932 TI - Human factors in decision making in major trauma in Camp Bastion, Afghanistan. AB - INTRODUCTION: The concentration of major trauma experience at Camp Bastion has allowed continuous improvements to occur in the patient pathway from the point of wounding to surgical treatment. These changes have involved clinical management as well as alterations to the physical layout of the hospital, training and decision making. Consideration of the human factors has been a major part of these improvements. METHODS: We describe the Camp Bastion patient pathway with the communication template that focused decision making at various key moments during damage control resuscitation and damage control surgery (DCR-DCS). This system identifies four key stages: 'command huddle', 'snap brief', 'sit-reps' (situation reports) and 'sign-out/debrief'. The attitude of staff to communication and decision making is also evaluated. RESULTS: Twenty cases admitted to Camp Bastion with battlefield injuries were studied from 6 September to 6 October 2012. Qualitative responses from 115 members of staff were collected. All patients were haemodynamically shocked with a median pH of 7.25 (range: 6.83-7.40) and a median of 18 units of mixed red cells and plasma were transfused. In 89% of instances, theatre staff were aware of what was required of them at the beginning of the case, 86% felt there were regular updates and 93% understood what was required of them as the case progressed. CONCLUSIONS: The evolution of the hospital at Camp Bastion has been a unique learning experience in the field of major trauma. The Defence Medical Services have responded with continuous innovation to optimise DCR-DCS for seriously injured patients. Together with the improvements in clinical care, a communication and decision making matrix was developed. Staff evaluation showed a high degree of satisfaction with the quality of communication. PMID- 26263933 TI - The spectrum of injuries resulting from posterior abdominal stab wounds: a South African experience. AB - INTRODUCTION: The spectrum of injury associated with anterior abdominal stab wounds (SWs) is well established. The literature on the spectrum of organ injury associated with SWs to the posterior abdomen, however, is limited. METHODS: We reviewed our experience of 105 consecutive patients who had established indications for laparotomy managed over a 4-year period in a high volume trauma service in South Africa. RESULTS: Of the 105 patients, 97 (92%) were male and the overall mean age was 24 years. Fifty-seven patients (54%) had immediate indications for laparotomy. The remaining 48 patients (46%) initially underwent active clinical observation and the indications for laparotomy became apparent during the observation period. Of the 105 laparotomies performed, 94 (90%) were positive and 11 (10%) were negative. Of the 94 positive laparotomies, 92 were therapeutic and 2 were non-therapeutic. A total of 176 organ injuries were identified: 50 (53%) of the 94 patients sustained a single organ injury while the remaining 44 (47%) sustained multiple organ injuries. The most commonly injured organs were the colon (n=63), spleen (n=21) and kidney (n=19). CONCLUSIONS: The pattern of intra-abdominal injuries secondary to SWs to the posterior abdomen is different to that seen with the anterior abdomen. Colonic injury is most commonly encountered, followed by injuries to the spleen and kidney. Clinicians must remain vigilant because of the potential for occult injuries. PMID- 26263934 TI - The incidence, spectrum and outcome of paediatric trauma managed by the Pietermaritzburg Metropolitan Trauma Service. AB - INTRODUCTION: The Pietermaritzburg Metropolitan Trauma Service (PMTS) has run a systematic quality improvement programme since 2006. A key component included the development and implementation of an effective surveillance system in the form of an electronic surgical registry (ESR). This study used data from the ESR to review the incidence, spectrum and outcome of paediatric trauma in Pietermaritzburg, South Africa. METHODS: The ESR was reviewed, and all cases of paediatric trauma managed between 1 January 2012 and 30 July 2014 were retrieved for analysis. RESULTS: During the study period, 1,041 paediatric trauma patients (724 male, 69.5%) were managed by the PMTS, averaging a monthly admission of 36. The mean age was 10.9 years (standard deviation: 5.4 years). The mechanism of injury (MOI) was blunt trauma in 753 patients (72.3%) and penetrating trauma in 170 (16.3%). Pedestrian vehicle collisions accounted for 21% of cases and motor vehicle collisions for a further 11%. Intentional trauma accounted for 282 patients (27.1%) and self-inflicted trauma for 14 cases (1.3%). Ninety patients admitted to the intensive care unit and fifty-one required high dependency unit admission. There were 17 deaths, equating to an in-hospital mortality rate of 1.7%. A total of 172 children died on the scene of an incident. There were 35 road traffic related deaths, 26 suicides by hanging, 27 deaths from blunt assault and 23 deaths from penetrating assault. The overall mortality rate for paediatric trauma was 18.2%. CONCLUSIONS: The ESR has proved to be an effective surveillance system and has enabled the accurate quantification of the burden of paediatric trauma in Pietermaritzburg. This has improved our understanding of the mechanisms and patterns of injury, and has identified a high incidence of intentional and penetrating trauma as well as road traffic collisions. These data can be used to guide strategies to reduce the burden of paediatric trauma in our environment. PMID- 26263935 TI - Outcome after conservatively managed intracapsular fractures of the femoral neck. AB - INTRODUCTION: In 2012, 2.6% of hip-fracture patients in the UK were treated conservatively. There is little data on outcome for these patients. However, one study demonstrated that though 30-day mortality is higher, mortality over the rest of the year is comparable with that in surgical groups. Therefore, we assessed conservatively managed patients in our unit. METHODS: Patients with intracapsular fractures of the femoral neck treated by conservative means between 2010 and 2012 inclusive were identified. Data were collected: American Society of Anaesthesiologists (ASA) grade, Nottingham Hip Fracture Score (NHFS), mobility, mortality (30 days and one year) and pain levels. RESULTS: Thirty-two patients formed the study cohort. Mean age was 85.6 years. Median ASA grade was 4. Mortality at 30 days and one year was 31.3% and 56.3%, respectively. There was one case of pneumonia and one of infection. Pressure sores or venous thromboembolism were not documented. Three patients underwent surgery once their health improved. In general, mobility was decreased, but 30.8% of patients could mobilise with two aids or a frame. Only two cases had ongoing problems with pain. CONCLUSIONS: Our data are similar to those published previously. Our patients were likely to have higher mortality data due to selection bias. Thirty-day mortality was significantly higher than the national average, but patients surviving 30 days had a prevalence of mortality similar to those managed by surgical means. Despite mobility decreasing from the pre-admission status, a considerable number of patients were free of pain and could mobilise. These data suggest that conservative management of intracapsular fractures of the femoral neck can produce acceptable results. PMID- 26263936 TI - Cost of infection after surgery for intracapsular fracture of the femoral neck. AB - INTRODUCTION: We investigated the financial and human costs of postoperative infection for intracapsular fracture of the femoral neck at a district general hospital in the UK. METHODS: Data on postoperative infections after surgical treatment for intracapsular fracture of the femoral neck were collected prospectively from June 2005 to April 2009. Infected patients were pairwise matched (1:2 ratio) with a non-infected group of patients from a database on hip fractures. Costs of additional surgery, duration of hospital stay, and opportunity costs were calculated using Primary Care Trust (PCT) tariffs and PCT specific data. RESULTS: A total of 525 patients were treated with total hip replacement (n=110) or hip hemiarthroplasty (n=415). Seventeen patients (3.2%) were identified as having a surgical-site infection. Eight (1.5%) deep infections and nine (1.7%) superficial infections were documented. Compared with the non infected group, duration of hospital stay and the prevalence of mortality doubled. Repeat surgery and the costs associated with hospital admission were increased significantly in the infected group. Mean financial loss associated with an infected patient was L7,726, whereas an uninfected patient brought L153 of profit to the hospital. When opportunity costs were considered, an infected patient represented L24,397 of lost income. CONCLUSIONS: Postoperative infection after surgical treatment for intracapsular fracture of the femoral neck has a significant negative impact on duration of hospital stay and financial costs, and demonstrates a trend towards an increase in the prevalence of mortality. PMID- 26263937 TI - Experience of managing open fractures of the lower limb at a major trauma centre. AB - INTRODUCTION: In April 2012 the John Radcliffe Hospital in Oxford became a major trauma centre (MTC). The British Orthopaedic Association and British Association of Plastic, Reconstructive and Aesthetic Surgeons joint standards for the management of open fractures of the lower limb (BOAST 4) require system-wide changes in referral practice that may be facilitated by the MTC and its associated major trauma network. METHODS: From 2008 to 2013 a multistep audit of compliance with BOAST 4 was conducted to assess referral patterns, timing of surgery and outcomes (surgical site infection rates), to determine changes following local intervention and the establishment of the MTC. RESULTS: Over the study period, 50 patients had soft tissue cover for an open lower limb fracture and there was a significant increase in the proportion of patients receiving definitive fixation in our centre (p=0.036). The median time from injury to soft tissue cover fell from 6.0 days to 3.5 days (p=0.051) and the median time from definitive fixation to soft tissue cover fell from 5.0 days to 2.0 days (p=0.003). The deep infection rate fell from 27% to 8% (p=0.247). However, in 2013 many patients still experienced a delay of >72 hours between injury and soft tissue cover, primarily owing to a lack of capacity for providing soft tissue cover. CONCLUSIONS: Our experience may be relevant to other MTCs seeking to identify barriers to optimising the management of patients with these injuries. PMID- 26263938 TI - Comparison of oncological safety between nipple sparing mastectomy and total mastectomy using propensity score matching. AB - INTRODCUTION: Although nipple sparing mastectomy (NSM) has attracted increased recognition as an alternative to traditional mastectomy approaches, its oncological safety is unclear. The purpose of this study was to compare the local recurrence rate between NSM and total mastectomy (TM). METHODS: Between 2003 and 2013, 121 and 557 patients with stage 0-III breast cancer underwent NSM and TM respectively. Multivariate Cox regression and propensity score models were used to compare the two groups. RESULTS: There was no significant difference in the five-year local recurrence rate between the NSM and TM groups (7.6% vs 4.9%, p=0.398). In multivariate analysis, NSM was not a risk factor for local recurrence (hazard ratio: 1.653, 95% confidence interval: 0.586-4.663, p=0.343). Propensity score matching found similar five-year local recurrence free survival rates between the two groups (92.3% vs 93.7%, p=0.655). CONCLUSIONS: Our results suggest that NSM may provide oncological safety comparable with mastectomy for carefully selected patients. PMID- 26263939 TI - Major cardiothoracic trauma: Eleven-year review of outcomes in the North West of England. AB - INTRODUCTION: Up to 15% of patients with cardiothoracic trauma require emergency surgery, and death can be prevented in a substantial proportion of this group. UK reports have emphasised the need for improvement in this field. We assessed major cardiothoracic trauma (MCT) outcomes in North West England over 11 years. METHODS: The database from the Trauma Audit and Research Network was used to retrieve data for all patients who had suffered MCT between 2000 and 2011 in North West England and the findings analysed. Trauma that led to thoracotomy/thoracoscopy or sternotomy was defined as MCT. RESULTS: A total of 146 patients were identified, and a considerable male predominance (88.4%) noted. A total of 54.1% had sustained penetrating cardiothoracic trauma. Also, 53.4% had been admitted to tertiary-care hospitals for trauma (TCHT) and 46.6% had been admitted to non-TCHT. Overall prevalence of mortality was 35.6%. No significant difference was found in mortality between TCHT vs non-TCHT. Prevalence of mortality was significantly higher in the subgroup of patients cared for exclusively in non-TCHT compared with patients transferred from non-TCHT to TCHT (41% vs 13.8%, p<0.05). CONCLUSIONS: No significant difference was demonstrated in length of stay in hospital/length of stay in the intensive treatment unit and prevalence of mortality between patients originally presenting in TCHT and those presenting in non-TCHT. However, patients transferred from non-TCHT to TCHT had a lower prevalence of mortality. These findings may constitute a valuable benchmark for comparison with results arising after introduction of trauma centres in the UK. PMID- 26263940 TI - Caustic ingestion injury of the upper aerodigestive tract in adults. AB - Adult ingestion of caustic substances is an unusual but serious surgical problem, with injuries likely to be more extensive than those in the corresponding paediatric population. After initial stabilisation and airway management, clinicians are presented with a complex multisystemic problem, frequently requiring a multidisciplinary approach involving several surgical disciplines and associated therapies. A new multidisciplinary team was convened to discuss complex ingestion injury in adults and established techniques were used to bring forward a proposed treatment algorithm. An algorithm may potentially improve clinical efficacy and risk in the management of these complex patients. PMID- 26263941 TI - Implementation of a novel emergency surgical unit significantly improves the management of gallstone pancreatitis. AB - INTRODUCTION: Emergency surgery is changing rapidly with a greater workload, early subspecialisation and centralisation of emergency care. We describe the impact of a novel emergency surgical unit (ESU) on the definitive management of patients with gallstone pancreatitis (GSP). METHODS: A comparative audit was undertaken for all admissions with GSP before and after the introduction of the ESU over a six-month period. The impact on compliance with British Society of Gastroenterology (BSG) guidelines was assessed. RESULTS: Thirty-five patients were treated for GSP between December 2013 and May 2014, after the introduction of the ESU. This was twice the nationally reported average for a UK trust over a six-month period. All patients received definitive management for their GSP and 100% of all suitable patients received treatment during the index admission or within two weeks of discharge. This was a significantly greater proportion than that prior to the introduction of the ESU (57%, p=0.0001) as well as the recently reported national average (34%). The mean length of total inpatient stay was reduced significantly after the ESU was introduced from 13.7 +/- 4.7 days to 7.8 +/- 2.1 days (p=0.03). The mean length of postoperative stay also fell significantly from 6.7 +/- 2.6 days to 1.8 +/- 0.8 days (p=0.001). CONCLUSIONS: A dedicated ESU following national recommendations for emergency surgery care by way of using dedicated emergency surgeons and a streamlined protocol for common presentations has been shown by audit of current practice to significantly improve the management of patients presenting to a busy district general hospital with GSP. PMID- 26263942 TI - Preventing intramedullary guidewire migration using an electrosurgery scratchpad. PMID- 26263943 TI - A new method to pass a suture through an outer table calvarial tunnel. PMID- 26263944 TI - Closed reduction of paediatric radial neck fractures. PMID- 26263945 TI - A technique for division of the sympathetic trunk during endoscopic thoracic sympathectomy. PMID- 26263946 TI - Splintage following supracondylar fracture in paediatrics. PMID- 26263947 TI - Preparation of the internal mammary vessels as recipients for free flap breast reconstruction. PMID- 26263948 TI - Endourological urethral dilation using a ureteral access sheath. PMID- 26263949 TI - Controlled eversion of the patella during total knee replacement surgery. PMID- 26263952 TI - Recent NICE guidance of interest to surgeons. PMID- 26263951 TI - The age of consent. PMID- 26263953 TI - Recurrent Warthin's tumour of the larynx. AB - Warthin's tumours, or adenolymphomas, present commonly as masses of the parotid glands and salivary tissue. However, in the existing literature, few cases of laryngeal adenolymphomas are described. We report the case of a 60-year-old woman with a recurrent right-sided laryngeal adenolymphoma, and discuss the difficulties in diagnosis and management. PMID- 26263954 TI - A rare case of a myofibroma presenting on the tongue. AB - Myofibromas are benign neoplasms of myofibroblastic origin, rarely encountered in the oral cavity. Limited awareness of the clinical features of these lesions risks misdiagnosis of more sinister pathology. The objective of this report is to highlight the potential diversity of oral lesions by describing an uncommon presentation of a myofibroma. The case reveals the diagnostic difficulties encountered, along with postoperative complications, which exemplify the remarkable healing capacity of the oral cavity. PMID- 26263955 TI - A case of severe necrotising pancreatitis following ampullary biopsy. AB - We present a case of necrotising pancreatitis following ampullary biopsy in a patient with Barrett's oesophagus. The patient needed multiple necrosectomies and several admissions to the intensive care unit. This report is only the third and most severe case of pancreatitis following ampullary biopsy, highlighting its importance as a complication. PMID- 26263956 TI - Radiological considerations and surgical planning in the treatment of giant parathyroid adenomas. AB - Giant parathyroid adenomas constitute a rare clinical entity, particularly in the developed world. We report the case of a 53-year-old woman where the initial ultrasonography significantly underestimated the size of the lesion. The subsequent size and weight of the adenoma (7 cm diameter, 27 g) combined with the severity of the hypercalcaemia raised the suspicion for the presence of a parathyroid carcinoma. This was later disproven by the surgical and histological findings. Giant parathyroid adenomas are encountered infrequently among patients with primary hyperparathyroidism, and appear to have distinct clinical and biochemical features related to specific genomic alterations. Cross-sectional imaging is mandated in the investigation of parathyroid adenomas presenting with severe hypercalcaemia as ultrasonography alone can underestimate their size and extent. This is important since it can impact on preoperative preparation and planning as well as the consent process as a thoracic approach may prove necessary for certain cases. PMID- 26263957 TI - Palatal and retropharyngeal injury secondary to intubation using the GlideScope(r) video laryngoscope. AB - INTRODUCTION: There are few reports of injury to the soft palate and retropharynx sustained during intubation with the GlideScope(r) video laryngoscope. Most reports are of isolated injury to the soft palate. CASE HISTORY: We describe a patient in whom the retropharynx was injured but the extent of the injury was not observed initially. The patient did not suffer severe sequelae from this injury. However, this injury can cause serious sequelae if it is not recognised (eg development of a retropharyngeal abscess). CONCLUSIONS: We recommend that any patient who sustains injury to the soft palate during intubation (particularly if the endotracheal tube passes through the soft palate) should be reviewed an otolaryngologist before removal of the endotracheal tube. PMID- 26263958 TI - New Polymorphic Forms of Pemetrexed Diacid and Their Use for the Preparation of Pharmaceutically Pure Amorphous and Hemipentahydrate Forms of Pemetrexed Disodium. AB - The preparation of stable amorphous pemetrexed disodium of pharmaceutical purity as well as the process optimization for the preparation of the hemipentahydrate form of pemetrexed disodium are described. Analytical methods for the polymorphic and chemical purity studies of pemetrexed disodium and pemetrexed diacid forms were developed. The physicochemical properties of the amorphous and hydrate forms of pemetrexed disodium, as well as new forms of pemetrexed diacid (a key synthetic intermediate) were studied by thermal analysis and powder X-ray diffraction. High-performance liquid chromatography and gas chromatography methods were used for the chemical purity and residual solvents determination. In order to study the polymorphic and chemical stability of the amorphous and hemipentahydrate forms, a hygroscopicity test (25 degrees C, 80% RH) was performed. Powder diffraction and high-performance liquid chromatography analyses revealed that the amorphous character and high chemical purity were preserved after the hygroscopicity test. The hemipentahydrate form transformed completely to the heptahydrate form of pemetrexed disodium. Both pemetrexed disodium forms were produced with high efficiency and pharmaceutical purity in a small commercial scale. Amorphous pemetrexed disodium was selected for further pharmaceutical development. Two new polymorphs (forms 1 and 2) of pemetrexed diacid were used for the preparation of high purity amorphous pemetrexed disodium. PMID- 26263959 TI - Imaging the Ultrafast Photoelectron Transfer Process in Alizarin-TiO2. AB - In this work, we adopt a quantum mechanical approach based on time-dependent density functional theory (TDDFT) to study the optical and electronic properties of alizarin supported on TiO2 nano-crystallites, as a prototypical dye-sensitized solar cell. To ensure proper alignment of the donor (alizarin) and acceptor (TiO2 nano-crystallite) levels, static optical excitation spectra are simulated using time-dependent density functional theory in response. The ultrafast photoelectron transfer from the dye to the cluster is simulated using an explicitly time dependent, one-electron TDDFT ansatz. The model considers the delta-pulse excitation of a single active electron localized in the dye to the complete set of energetically accessible, delocalized molecular orbitals of the dye/nano crystallite complex. A set of quantum mechanical tools derived from the transition electronic flux density is introduced to visualize and analyze the process in real time. The evolution of the created wave packet subject to absorbing boundary conditions at the borders of the cluster reveal that, while the electrons of the aromatic rings of alizarin are heavily involved in an ultrafast charge redistribution between the carbonyl groups of the dye molecule, they do not contribute positively to the electron injection and, overall, they delay the process. PMID- 26263960 TI - Antiproliferative and Structure Activity Relationships of Amaryllidaceae Alkaloids. AB - The antiproliferative activity of a set of seven natural Amaryllidaceae alkaloids and 32 derivatives against four cancer cell lines (A2780, SW1573, T47-D and WiDr) was determined. The best antiproliferative activities were achieved with alkaloids derived from pancracine (2), haemanthamine (6) and haemantidine (7). For each skeleton, some structure-activity relationships were outlined. PMID- 26263961 TI - Synthesis of a Spirocyclic Oxetane-Fused Benzimidazole. AB - A new synthesis of 2-oxa-7-azaspiro[3.5]nonane is described. Spirocyclic oxetanes, including 2-oxa-6-azaspiro[3.3]heptane were converted into o cycloalkylaminoacetanilides for oxidative cyclizations using Oxone(r) in formic acid. The expanded spirocyclic oxetane successfully gave the [1,2-a] ring-fused benzimidazole. X-ray crystal structure of the resultant new tetracyclic system, 1',2'-dihydro-4'H-spiro[oxetane-3,3'-pyrido[1,2-a]benzimidazole] and the azetidine ring-opened adduct, N-(2-acetamido-4-bromophenyl)-N-{[3-(chloromethyl) oxetan-3-yl]methyl}acetamide are disclosed. PMID- 26263962 TI - Natural Compounds from Saffron and Bear Bile Prevent Vision Loss and Retinal Degeneration. AB - All retinal disorders, regardless of their aetiology, involve the activation of oxidative stress and apoptosis pathways. The administration of neuroprotective factors is crucial in all phases of the pathology, even when vision has been completely lost. The retina is one of the most susceptible tissues to reactive oxygen species damage. On the other hand, proper development and functioning of the retina requires a precise balance between the processes of proliferation, differentiation and programmed cell death. The life-or-death decision seems to be the result of a complex balance between pro- and anti-apoptotic signals. It has been recently shown the efficacy of natural products to slow retinal degenerative process through different pathways. In this review, we assess the neuroprotective effect of two compounds used in the ancient pharmacopoeia. On one hand, it has been demonstrated that administration of the saffron constituent safranal to P23H rats, an animal model of retinitis pigmentosa, preserves photoreceptor morphology and number, the capillary network and the visual response. On the other hand, it has been shown that systemic administration of tauroursodeoxycholic acid (TUDCA), the major component of bear bile, to P23H rats preserves cone and rod structure and function, together with their contact with postsynaptic neurons. The neuroprotective effects of safranal and TUDCA make these compounds potentially useful for therapeutic applications in retinal degenerative diseases. PMID- 26263963 TI - Aspects of a Distinct Cytotoxicity of Selenium Salts and Organic Selenides in Living Cells with Possible Implications for Drug Design. AB - Selenium is traditionally considered as an antioxidant element and selenium compounds are often discussed in the context of chemoprevention and therapy. Recent studies, however, have revealed a rather more colorful and diverse biological action of selenium-based compounds, including the modulation of the intracellular redox homeostasis and an often selective interference with regulatory cellular pathways. Our basic activity and mode of action studies with simple selenium and tellurium salts in different strains of Staphylococcus aureus (MRSA) and Saccharomyces cerevisiae indicate that such compounds are sometimes not particularly toxic on their own, yet enhance the antibacterial potential of known antibiotics, possibly via the bioreductive formation of insoluble elemental deposits. Whilst the selenium and tellurium compounds tested do not necessarily act via the generation of Reactive Oxygen Species (ROS), they seem to interfere with various cellular pathways, including a possible inhibition of the proteasome and hindrance of DNA repair. Here, organic selenides are considerably more active compared to simple salts. The interference of selenium (and tellurium) compounds with multiple targets could provide new avenues for the development of effective antibiotic and anticancer agents which may go well beyond the traditional notion of selenium as a simple antioxidant. PMID- 26263964 TI - Caesalpinia decapetala Extracts as Inhibitors of Lipid Oxidation in Beef Patties. AB - In this study we investigated the effects of Caesalpinia decapetala (CD) extracts on lipid oxidation in ground beef patties. Plant extracts and butylated hydroxytoluene (BHT) were individually added to patties at both 0.1% and 0.5% (w/w) concentrations. We assessed the antioxidant efficacy of CD by the ferric reducing antioxidant power (FRAP) assay and evaluated their potential as natural antioxidants for meat preservation by thiobarbituric acid reactive substance (TBARS) values, hexanal content, fatty acid composition and color parameters. These were tested periodically during 11 days of refrigerated storage. TBARS levels were significantly lower (p <= 0.05) in the samples containing plant extracts or BHT than in the non-treated control. In addition, the beef patties formulated with the selected plant extracts showed significantly (p <= 0.05) better color stability than those without antioxidants. These results indicate that edible plant extracts are promising sources of natural antioxidants and can potentially be used as functional preservatives in meat products. PMID- 26263965 TI - Cordyceps militaris (L.) Link Fruiting Body Reduces the Growth of a Non-Small Cell Lung Cancer Cell Line by Increasing Cellular Levels of p53 and p21. AB - Cordyceps militaris (L.) Link, an edible entomopathogenic fungus widely used in traditional Chinese medicine, has numerous potential medicinal properties including antitumor activity. The methanolic extract of C. militaris fruiting body was recently shown to have tumor cell growth inhibitory activity in several human tumor cell lines. Nonetheless, the mechanism of action involved is still not known. This work aimed at further studying the effect of the methanolic extract of C. militaris regarding its antitumor mechanism of action, using the non-small cell lung cancer cell line (NCI-H460) as a model. Results showed that treatment with the extract decreased cellular proliferation, induced cell cycle arrest at G0/G1 and increased apoptosis. In addition, the extract increased the levels of p53 and p21. Moreover, an increase in p-H2A.X and 53BP1 levels, together with an increase in the number of 53BP1 foci/cell (all indicative of DNA damage), were also observed after treatment with the extract. This work suggests that this extract affected NCI-H460 cellular viability through a mechanism involving DNA damage and p53 activation. This further supports the potential of this extract as a source of bioactive compounds, which may be used in anticancer strategies. PMID- 26263966 TI - Synthesis and Fungicidal Activity of beta-Carboline Alkaloids and Their Derivatives. AB - A series of beta-Carboline derivatives were designed, synthesized, and evaluated for their fungicidal activities in this study. Several derivatives electively exhibited fungicidal activities against some fungi. Especially, compound F5 exhibited higher fungicidal activity against Rhizoctonia solani (53.35%) than commercial antiviral agent validamycin (36.4%); compound F16 exhibited high fungicidal activity against Oospora citriaurantii ex Persoon (43.28%). Some of the alkaloids and their derivatives (compounds F4 and F25) exhibited broad spectrum fungicidal activity. Specifically, compound F4 exhibited excellent high broad-spectrum fungicidal activity in vitro, and the curative and protection activities against P. litchi in vivo reached 92.59% and 59.26%, respectively. The new derivative, F4, with optimized physicochemical properties, obviously exhibited higher activities both in vitro and in vivo; therefore, F4 may be used as a new lead structure for the development of fungicidal drugs. PMID- 26263967 TI - Qualitative and Quantitative Analysis of Major Triterpenoids in Alismatis Rhizoma by High Performance Liquid Chromatography/Diode-Array Detector/Quadrupole-Time-of Flight Mass Spectrometry and Ultra-Performance Liquid Chromatography/Triple Quadrupole Mass Spectrometry. AB - Alismatis Rhizoma (AMR) is a well-known natural medicine with a long history in Chinese medicine and has been commonly used for treating a wide range of ailments related to dysuria, edema, nephropathy, hyperlipidaemia, diabetes, inflammation as well as tumors in clinical applications. Most beneficial effects of AMR are attributed to the presence of protostane terpenoids, the major active ingredients of Alismatis Rhizoma (AMR). In this study, a systematic high performance liquid chromatography/diode-array detector/quadrupole-time-of-flight mass spectrometry (HPLC-DAD-Q-TOF MS) and ultra-performance liquid chromatography/triple quadrupole mass spectrometry (UPLC-QqQ MS) method was developed for qualitative and quantitative analyses of the major AMR triterpenoids. First, a total of 25 triterpenoid components, including 24 known compounds and one new compound were identified by comparison with UV spectra, molecular ions and fragmentation behaviors of reference standards or the literature. Second, an efficient method was established for the rapid simultaneous determination of 14 representative triterpenoids by UPLC-QqQ MS. Forty-three batches of AMR were analyzed with linearity (r, 0.9980-0.9999), intra-day precision (RSD, 1.18%-3.79%), inter-day precision (RSD, 1.53%-3.96%), stability (RSD, 1.32%-3.97%), repeatability (RSD, 2.21%-4.25%), and recovery (98.11%-103.8%). These results indicated that new approaches combining HPLC-DAD-Q-TOF MS and UPLC-QqQ MS are applicable in the qualitative and quantitative analysis of AMR. PMID- 26263968 TI - Combination of Abeta Secretion and Oxidative Stress in an Alzheimer-Like Cell Line Leads to the Over-Expression of the Nucleotide Excision Repair Proteins DDB2 and XPC. AB - Repair of oxidative DNA damage, particularly Base Excision Repair (BER), impairment is often associated with Alzheimer's disease pathology. Here, we aimed at investigating the complete Nucleotide Excision Repair (NER), a DNA repair pathway involved in the removal of bulky DNA adducts, status in an Alzheimer-like cell line. The level of DNA damage was quantified using mass spectrometry, NER gene expression was assessed by qPCR, and the NER protein activity was analysed through a modified version of the COMET assay. Interestingly, we found that in the presence of the Amyloid beta peptide (Abeta), NER factors were upregulated at the mRNA level and that NER capacities were also specifically increased following oxidative stress. Surprisingly, NER capacities were not differentially improved following a typical NER-triggering of ultraviolet C (UVC) stress. Oxidative stress generates a differential and specific DNA damage response in the presence of Abeta. We hypothesized that the release of NER components such as DNA damage binding protein 2 (DDB2) and Xeroderma Pigmentosum complementation group C protein (XPC) following oxidative stress might putatively involve their apoptotic role rather than DNA repair function. PMID- 26263969 TI - Effects of Surface-Deacetylated Chitin Nanofibers in an Experimental Model of Hypercholesterolemia. AB - This study evaluated the effects of oral administration of surface-deacetylated chitin nanofibers (SDACNFs) on hypercholesterolemia using an experimental model. All rats were fed a high cholesterol diet with 1% w/w cholesterol and 0.5% w/w cholic acid for 28 days. Rats were divided equally into four groups: the control group was administered 0.05% acetic acid dissolved in tap water, and the SDACNF, chitosan (CS), and cellulose nanofiber (CLNF) groups were administered 0.1% CNF, CS, or CLNF dissolved in the tap water, respectively, during the experimental period. Changes in body weight, intake of food and water, and organ weight were measured. Serum blood chemistry and histopathological examination of the liver were performed. Administration of SDACNF did not affect body weight change, food and water intake, or organ weights. Administration of SDACNF and CS decreased the diet-induced increase in serum total cholesterol, chylomicron, very-low-density lipoprotein, and phospholipid levels on day 14. Moreover, oral administration of SDACNFs suppressed the increase of alanine transaminase levels on day 29 and suppressed vacuolar degeneration and accumulation of lipid droplets in liver tissue. These data indicate that SDACNF has potential as a functional food for patients with hypercholesterolemia. PMID- 26263970 TI - A Single Nucleotide Polymorphism near the CYP17A1 Gene Is Associated with Left Ventricular Mass in Hypertensive Patients under Pharmacotherapy. AB - Cytochrome P450 17A1 (CYP17A1) catalyses the formation and metabolism of steroid hormones. They are involved in blood pressure (BP) regulation and in the pathogenesis of left ventricular hypertrophy. Therefore, altered function of CYP17A1 due to genetic variants may influence BP and left ventricular mass. Notably, genome wide association studies supported the role of this enzyme in BP control. Against this background, we investigated associations between single nucleotide polymorphisms (SNPs) in or nearby the CYP17A1 gene with BP and left ventricular mass in patients with arterial hypertension and associated cardiovascular organ damage treated according to guidelines. Patients (n = 1007, mean age 58.0 +/- 9.8 years, 83% men) with arterial hypertension and cardiac left ventricular ejection fraction (LVEF) >= 40% were enrolled in the study. Cardiac parameters of left ventricular mass, geometry and function were determined by echocardiography. The cohort comprised patients with coronary heart disease (n = 823; 81.7%) and myocardial infarction (n = 545; 54.1%) with a mean LVEF of 59.9% +/- 9.3%. The mean left ventricular mass index (LVMI) was 52.1 +/- 21.2 g/m2.7 and 485 (48.2%) patients had left ventricular hypertrophy. There was no significant association of any investigated SNP (rs619824, rs743572, rs1004467, rs11191548, rs17115100) with mean 24 h systolic or diastolic BP. However, carriers of the rs11191548 C allele demonstrated a 7% increase in LVMI (95% CI: 1%-12%, p = 0.017) compared to non-carriers. The CYP17A1 polymorphism rs11191548 demonstrated a significant association with LVMI in patients with arterial hypertension and preserved LVEF. Thus, CYP17A1 may contribute to cardiac hypertrophy in this clinical condition. PMID- 26263971 TI - Interleukin-17A Gene Expression in Morbidly Obese Women. AB - Data from recent studies conducted in rodent models and humans suggest that interleukin-17A (IL-17A) plays a role in the induction of inflammation in adipose tissue during obesity. The aim of this study was to assess the gene expression of IL-17A in adipose tissue of morbidly obese patients. We used RT-PCR to evaluate the expression of IL-17A and several adipo/cytokines in the visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) of 10 normal-weight control women (BMI < 25 kg/m2) and 30 morbidly obese women (MO, BMI > 40 kg/m2). We measured serum levels of IL-17A and adipo/cytokines in MO and normal weight women. IL-17A expression was significantly higher in VAT than in SAT in MO patients (p = 0.0127). It was very low in normal-weight controls in both VAT and SAT tissues. We found positive correlations between IL-17A and IL-6, lipocalin-2 and resistin in VAT of MO patients. The circulating level of IL-17A was higher in the normal-weight group than the MO patients (p = 0.032), and it was significantly related to adiponectin and TNFRII levels. In conclusion, IL-17A expression in VAT is increased in morbidly obese women, which suggests a link between obesity and innate immunity in low-grade chronic inflammation in morbidly obese women. PMID- 26263972 TI - Development of Ophiocordyceps sinensis through Plant-Mediated Interkingdom Host Colonization. AB - Ophiocordyceps sinensis is a well-known entomogenous and medicinal fungus. After its anamorphs parasitize the larvae of the genus Thitarodes, fruit-bodies may form to be used as medicine. However, its developmental mechanisms remain unknown. The distribution of O. sinensis was determined in different tissues of the Thitarodes larvae and the dominant plant species using real-time quantitative polymerase chain reaction (qPCR) and fluorescence in situ hybridization (FISH) technique, respectively. We found that more fungal material was located in plants than in larvae, especially in Ranunculus tanguticus. A considerable amount was detected in larval intestinal-wall and plant roots. It is suggested that plants are the potential hosts of O. sinensis, which modifies our understanding of the life cycle of O. sinensis and indicates that the phytophagous larvae may become infected as they feed. Our research may contribute to the study of systematic evolution and population ecology of O. sinensis, elucidate its developmental mechanism and promote sustainable harvesting. PMID- 26263975 TI - Features in the Lipid Status of Two Generations of Fingerlings (0+) of Atlantic Salmon (Salmo salar L.) Inhabiting the Arenga River (Kola Peninsula). AB - The present research focused on determining the lipid status of salmon fingerlings (0+) in early development after dispersal form groups of spawning nests in biotopes of different hydrological conditions. The revealed qualitative and quantitative differences in the levels of phospholipids and fatty acids among two generations of Atlantic salmon fingerlings (0+) living in different biotopes of the Arenga River (a tributary of the Varzuga River) may be associated with the peculiarities of their genetically determined processes of the biosynthesis and modification of individual lipid classes and trophoecological factors (food spectrum, quality and availability of food objects, and hydrological regime). The research was organized to observe the dynamics of these developmental changes from ages 0+ to 2+. PMID- 26263973 TI - Molecular Mechanisms to Control Post-Transplantation Hepatitis B Recurrence. AB - Hepatitis B often progresses to decompensated liver cirrhosis requiring orthotopic liver transplantation (OLT). Although newer nucleos(t)ide analogues result in >90% viral and hepatitis activity control, severely decompensated patients still need OLT because of drug-resistant virus, acute exacerbation, or hepatocellular carcinoma. Acute hepatitis B is also an indication for OLT, because it can progress to fatal acute liver failure. After OLT, the hepatitis B recurrence rate is >80% without prevention, while >90% of transplant recipients are clinically controlled with combined hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogue treatment. However, long-term HBIG administration is associated with several unresolved issues, including limited availability and extremely high cost; therefore, several treatment protocols with low-dose HBIG, combined with nucleos(t)ide analogues, have been investigated. Another approach is to induce self-producing anti-hepatitis B virus (HBV) antibodies using an HBV envelope (HBs) antigen vaccine. Patients who are not HBV carriers, such as those with acutely infected liver failure, are good candidates for vaccination. For chronic HBV carrier liver cirrhosis patients, a successful vaccine response can only be achieved in selected patients, such as those treated with experimentally reduced immunosuppression protocols. The present protocol for post-OLT HBV control and the future prospects of newer treatment strategies are reviewed. PMID- 26263974 TI - Molecular Classification and Pharmacogenetics of Primary Plasma Cell Leukemia: An Initial Approach toward Precision Medicine. AB - Primary plasma cell leukemia (pPCL) is a rare and aggressive variant of multiple myeloma (MM) which may represent a valid model for high-risk MM. This disease is associated with a very poor prognosis, and unfortunately, it has not significantly improved during the last three decades. New high-throughput technologies have allowed a better understanding of the molecular basis of this disease and moved toward risk stratification, providing insights for targeted therapy studies. This knowledge, added to the pharmacogenetic profile of new and old agents in the analysis of efficacy and safety, could contribute to help clinical decisions move toward a precision medicine and a better clinical outcome for these patients. In this review, we describe the available literature concerning the genomic characterization and pharmacogenetics of plasma cell leukemia (PCL). PMID- 26263976 TI - Economic Assessment of Supercritical CO2 Extraction of Waxes as Part of a Maize Stover Biorefinery. AB - To date limited work has focused on assessing the economic viability of scCO2 extraction to obtain waxes as part of a biorefinery. This work estimates the economic costs for wax extraction from maize stover. The cost of manufacture (COM) for maize stover wax extraction was found to be ? 88.89 per kg of wax, with the fixed capital investment (FCI) and utility costs (CUT) contributing significantly to the COM. However, this value is based solely on scCO2 extraction of waxes and does not take into account the downstream processing of the biomass following extraction. The cost of extracting wax from maize stover can be reduced by utilizing pelletized leaves and combusting the residual biomass to generate electricity. This would lead to an overall cost of ? 10.87 per kg of wax (based on 27% combustion efficiency for electricity generation) and ?4.56 per kg of wax (based on 43% combustion efficiency for electricity generation). A sensitivity analysis study showed that utility costs (cost of electricity) had the greatest effect on the COM. PMID- 26263977 TI - Brain-Specific Cytoskeletal Damage Markers in Cerebrospinal Fluid: Is There a Common Pattern between Amyotrophic Lateral Sclerosis and Primary Progressive Multiple Sclerosis? AB - Many neurodegenerative disorders share a common pathophysiological pathway involving axonal degeneration despite different etiological triggers. Analysis of cytoskeletal markers such as neurofilaments, protein tau and tubulin in cerebrospinal fluid (CSF) may be a useful approach to detect the process of axonal damage and its severity during disease course. In this article, we review the published literature regarding brain-specific CSF markers for cytoskeletal damage in primary progressive multiple sclerosis and amyotrophic lateral sclerosis in order to evaluate their utility as a biomarker for disease progression in conjunction with imaging and histological markers which might also be useful in other neurodegenerative diseases associated with affection of the upper motor neurons. A long-term benefit of such an approach could be facilitating early diagnostic and prognostic tools and assessment of treatment efficacy of disease modifying drugs. PMID- 26263978 TI - Progress and Prospects of Anti-HBV Gene Therapy Development. AB - Despite the availability of an effective vaccine against hepatitis B virus (HBV), chronic infection with the virus remains a major global health concern. Current drugs against HBV infection are limited by emergence of resistance and rarely achieve complete viral clearance. This has prompted vigorous research on developing better drugs against chronic HBV infection. Advances in understanding the life cycle of HBV and improvements in gene-disabling technologies have been impressive. This has led to development of better HBV infection models and discovery of new drug candidates. Ideally, a regimen against chronic HBV infection should completely eliminate all viral replicative intermediates, especially covalently closed circular DNA (cccDNA). For the past few decades, nucleic acid-based therapy has emerged as an attractive alternative that may result in complete clearance of HBV in infected patients. Several genetic anti HBV strategies have been developed. The most studied approaches include the use of antisense oligonucleotides, ribozymes, RNA interference effectors and gene editing tools. This review will summarize recent developments and progress made in the use of gene therapy against HBV. PMID- 26263979 TI - RNase L Cleavage Products Promote Switch from Autophagy to Apoptosis by Caspase Mediated Cleavage of Beclin-1. AB - Autophagy and apoptosis share regulatory molecules enabling crosstalk in pathways that affect cellular homeostasis including response to viral infections and survival of tumor cells. Ribonuclease L (RNase L) is an antiviral endonuclease that is activated in virus-infected cells and cleaves viral and cellular single stranded RNAs to produce small double-stranded RNAs with roles in amplifying host responses. Activation of RNase L induces autophagy and apoptosis in many cell types. However, the mechanism by which RNase L mediates crosstalk between these two pathways remains unclear. Here we show that small dsRNAs produced by RNase L promote a switch from autophagy to apoptosis by caspase-mediated cleavage of Beclin-1, terminating autophagy. The caspase 3-cleaved C-terminal fragment of Beclin-1 enhances apoptosis by translocating to the mitochondria along with proapoptotic protein, Bax, and inducing release of cytochrome C to the cytosol. Cleavage of Beclin-1 determines switch to apoptosis since expression of caspase resistant Beclin-1 inhibits apoptosis and sustains autophagy. Moreover, inhibiting RNase L-induced autophagy promotes cell death and inhibiting apoptosis prolongs autophagy in a cross-inhibitory mechanism. Our results demonstrate a novel role of RNase L generated small RNAs in cross-talk between autophagy and apoptosis that impacts the fate of cells during viral infections and cancer. PMID- 26263980 TI - Validation of FRET Assay for the Screening of Growth Inhibitors of Escherichia coli Reveals Elongasome Assembly Dynamics. AB - The increase in antibiotic resistant bacteria demands the development of new antibiotics against preferably new targets. The common approach is to test compounds for their ability to kill bacteria or to design molecules that inhibit essential protein activities in vitro. In the first case, the mode of action of the drug is unknown and in the second case, it is not known whether the compound will pass the impermeable barrier of the bacterial envelope. We developed an assay that detects the target of a compound, as well as its ability to pass the membrane(s) simultaneously. The Escherichia coli cytoskeletal protein MreB recruits protein complexes (elongasomes) that are essential for cell envelope growth. An in cell Forster Resonance Energy Transfer (FRET) assay was developed to detect the interaction between MreB molecules and between MreB and the elongasome proteins RodZ, RodA and PBP2. Inhibition of the polymerization of MreB by S-(3,4-dichlorobenzyl) isothiourea (A22) or of the activity of PBP2 by mecilinam resulted in loss or reduction of all measured interactions. This suggests that the interactions between the elongasome proteins are governed by a combination of weak affinities and substrate availability. This validated in cell FRET assay can be used to screen for cell envelope growth inhibitors. PMID- 26263981 TI - High Expression of LAMP3 Is a Novel Biomarker of Poor Prognosis in Patients with Esophageal Squamous Cell Carcinoma. AB - Lysosomal-associated membrane protein 3 (LAMP3), identified as a molecular marker of mature dendritic cells, is one of the LAMP family members. Its expression was induced by hypoxia, and was associated with hypoxia mediated metastasis in breast and cervical cancers. However, epithelial expression of LAMP3 and its prognostic value in esophageal squamous cell carcinoma (ESCC) is still unknown. In the current study, mRNA expression of LAMP3 in 157 ESCC tissues and 50 adjacent normal tissues was detected by quantitative real-time PCR (qRT-PCR). LAMP3 protein expression in 46 paired cancerous and normal tissues was detected by immunohistochemistry (IHC). Then, DNA copy number was examined to observe its potential correlation with mRNA expression. The results showed that both mRNA and protein expression level of LAMP3 was significantly higher in cancerous tissues compared with normal controls (p < 0.001). LAMP3 DNA copy number was amplified in 70% of ESCC tissues and positive correlated with mRNA expression (p = 0.037). Furthermore, patients with higher LAMP3 expression had worse overall survival (HR = 1.90, 95% CI = 1.17-3.09, p = 0.010) and disease-free survival (HR = 1.80, 95% CI = 1.18-2.74, p = 0.006). In conclusion, our results suggest that epithelial LAMP3 expression is an independent prognostic biomarker for ESCC. PMID- 26263982 TI - Unveiling the Mode of Action of Two Antibacterial Tanshinone Derivatives. AB - In this study, 2-(N-pyrrolidine-alkyl) tanshinones bearing pyrrolidine groups were synthesized and the antibacterial mechanism was explored. These derivatives selectively elicited antibacterial activity against Gram-positive bacteria. Moreover, their antibacterial activities were time-, concentration-dependent and persistent. It appeared that Fenton-mediated hydroxyl radicals were involved, and the disruption of cell membranes was observed. This study indicates that 2-(N pyrrolidine-alkyl) tanshinones might be potential candidates as antibacterial agents. PMID- 26263983 TI - MiR-30b Is Involved in the Homocysteine-Induced Apoptosis in Human Coronary Artery Endothelial Cells by Regulating the Expression of Caspase 3. AB - Homocysteine (Hcy) is an independent risk factor for a variety of cardiovascular diseases, such as coronary heart disease, hypertension, stroke, etc. There is a close relationship between the vascular endothelial cell apoptosis and these diseases. Recent studies have shown homocysteine can induce apoptosis in endothelial cells, which may be an important mechanism for the development of theses cardiovascular diseases. Although there are several reports about how the Hcy induces apoptosis in endothelial cells, the exact mechanism is not fully understood. MicroRNAs are small, non-coding RNA. Previous studies have shown that there is a close relationship between several microRNAs and cell apoptosis. However, there are no studies about the role of microRNAs in Hcy-induced apoptosis in endothelial cells so far. In this study, we constructed the model of homocysteine-induced apoptosis in human coronary artery endothelial cells (HCAECs) and found miR-30b was significantly down-regulated by 1 mmol/L Hcy. In addition, overexpression of miR-30b can improve the Hcy-induced apoptosis in HCAECs by downregulating caspase-3 expression. Therefore, miR-30b may play an important role in Hcy-induced apoptosis in endothelial cells. PMID- 26263985 TI - Scalable and Cost-Effective Assignment of Mobile Crowdsensing Tasks Based on Profiling Trends and Prediction: The ParticipAct Living Lab Experience. AB - Nowadays, sensor-rich smartphones potentially enable the harvesting of huge amounts of valuable sensing data in urban environments, by opportunistically involving citizens to play the role of mobile virtual sensors to cover Smart City areas of interest. This paper proposes an in-depth study of the challenging technical issues related to the efficient assignment of Mobile Crowd Sensing (MCS) data collection tasks to volunteers in a crowdsensing campaign. In particular, the paper originally describes how to increase the effectiveness of the proposed sensing campaigns through the inclusion of several new facilities, including accurate participant selection algorithms able to profile and predict user mobility patterns, gaming techniques, and timely geo-notification. The reported results show the feasibility of exploiting profiling trends/prediction techniques from volunteers' behavior; moreover, they quantitatively compare different MCS task assignment strategies based on large-scale and real MCS data campaigns run in the ParticipAct living lab, an ongoing MCS real-world experiment that involved more than 170 students of the University of Bologna for more than one year. PMID- 26263984 TI - Evaluation of Antioxidant, Antidiabetic and Anticholinesterase Activities of Smallanthus sonchifolius Landraces and Correlation with Their Phytochemical Profiles. AB - The present study aimed to investigate the phytochemical profile of leaf methanol extracts of fourteen Smallanthus sonchifolius (yacon) landraces and their antioxidant, anticholinesterase and antidiabetic activities that could lead to the finding of more effective agents for the treatment and management of Alzheimer's disease and diabetes. For this purpose, antioxidant activity was assessed using different tests: ferric reducing ability power (FRAP), 2,2 diphenyl-1-picryl hydrazyl (DPPH), nitric oxide (NO) and superoxide (O2-) scavenging and lipid peroxidation inhibition assays. Anticholinesterase activity was investigated by quantifying the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, whereas antidiabetic activity was investigated by alpha-amylase and alpha-glucosidase inhibition tests. To understand the contribution of metabolites, phytochemical screening was also performed by high performance liquid chromatography-diode array detector (HPLC DAD) system. Among all, methanol extract of PER09, PER04 and ECU44 landraces exhibited the highest relative antioxidant capacity index (RACI). ECU44 was found to be rich in 4,5-di-O-caffeoylquinic acid (CQA) and 3,5-di-O-CQA and displayed a good alpha-amylase and alpha-glucosidase inhibition, showing the lowest IC50 values. Flavonoids, instead, seem to be involved in the AChE and BChE inhibition. The results of this study revealed that the bioactive compound content differences could be determinant for the medicinal properties of this plant especially for antioxidant and antidiabetic activities. PMID- 26263986 TI - An Ultrasonic Multiple-Access Ranging Core Based on Frequency Shift Keying Towards Indoor Localization. AB - This paper describes a new approach and implementation methodology for indoor ranging based on the time difference of arrival using code division multiple access with ultrasound signals. A novel implementation based on a field programmable gate array using finite impulse response filters and an optimized correlation demodulator implementation for ultrasound orthogonal signals is developed. Orthogonal codes are modulated onto ultrasound signals using frequency shift keying with carrier frequencies of 24.5 kHz and 26 kHz. This implementation enhances the possibilities for real-time, embedded and low-power tracking of several simultaneous transmitters. Due to the high degree of parallelism offered by field programmable gate arrays, up to four transmitters can be tracked simultaneously. The implementation requires at most 30% of the available logic gates of a Spartan-6 XC6SLX45 device and is evaluated on accuracy and precision through several ranging topologies. In the first topology, the distance between one transmitter and one receiver is evaluated. Afterwards, ranging analyses are applied between two simultaneous transmitters and one receiver. Ultimately, the position of the receiver against four transmitters using trilateration is also demonstrated. Results show enhanced distance measurements with distances ranging from a few centimeters up to 17 m, while keeping a centimeter-level accuracy. PMID- 26263987 TI - Fibre Optic Sensors for Structural Health Monitoring of Aircraft Composite Structures: Recent Advances and Applications. AB - In-service structural health monitoring of composite aircraft structures plays a key role in the assessment of their performance and integrity. In recent years, Fibre Optic Sensors (FOS) have proved to be a potentially excellent technique for real-time in-situ monitoring of these structures due to their numerous advantages, such as immunity to electromagnetic interference, small size, light weight, durability, and high bandwidth, which allows a great number of sensors to operate in the same system, and the possibility to be integrated within the material. However, more effort is still needed to bring the technology to a fully mature readiness level. In this paper, recent research and applications in structural health monitoring of composite aircraft structures using FOS have been critically reviewed, considering both the multi-point and distributed sensing techniques. PMID- 26263988 TI - An Electrochemical Glucose Sensor Based on Zinc Oxide Nanorods. AB - A glucose electrochemical sensor based on zinc oxide (ZnO) nanorods was investigated. The hydrothermal sol-gel growth method was utilized to grow ZnO nanorods on indium tin oxide-coated glass substrates. The total active area of the working electrode was 0.3 * 0.3 cm2 where titanium metal was deposited to enhance the contact. Well aligned hexagonal structured ZnO nanorods with a diameter from 68 to 116 nm were obtained. The excitonic peak obtained from the absorbance spectroscopy was observed at ~370 nm. The dominant peak of Raman spectroscopy measurement was at 440 cm(-1), matching with the lattice vibration of ZnO. The uniform distribution of the GOx and Nafion membrane that has been done using spin coating technique at 4000 rotations per minute helps in enhancing the ion exchange and increasing the sensitivity of the fabricated electrochemical sensor. The amperometric response of the fabricated electrochemical sensor was 3 s. The obtained sensitivity of the fabricated ZnO electrochemical sensor was 10.911 mA/mM.cm2 and the lower limit of detection was 0.22 uM. PMID- 26263990 TI - RGB-D SLAM Combining Visual Odometry and Extended Information Filter. AB - In this paper, we present a novel RGB-D SLAM system based on visual odometry and an extended information filter, which does not require any other sensors or odometry. In contrast to the graph optimization approaches, this is more suitable for online applications. A visual dead reckoning algorithm based on visual residuals is devised, which is used to estimate motion control input. In addition, we use a novel descriptor called binary robust appearance and normals descriptor (BRAND) to extract features from the RGB-D frame and use them as landmarks. Furthermore, considering both the 3D positions and the BRAND descriptors of the landmarks, our observation model avoids explicit data association between the observations and the map by marginalizing the observation likelihood over all possible associations. Experimental validation is provided, which compares the proposed RGB-D SLAM algorithm with just RGB-D visual odometry and a graph-based RGB-D SLAM algorithm using the publicly-available RGB-D dataset. The results of the experiments demonstrate that our system is quicker than the graph-based RGB-D SLAM algorithm. PMID- 26263989 TI - Diazonium Chemistry for the Bio-Functionalization of Glassy Nanostring Resonator Arrays. AB - Resonant glassy nanostrings have been employed for the detection of biomolecules. These devices offer high sensitivity and amenability to large array integration and multiplexed assays. Such a concept has however been impaired by the lack of stable and biocompatible linker chemistries. Diazonium salt reduction-induced aryl grafting is an aqueous-based process providing strong chemical adhesion. In this work, diazonium-based linker chemistry was performed for the first time on glassy nanostrings, which enabled the bio-functionalization of such devices. Large arrays of nanostrings with ultra-narrow widths down to 10 nm were fabricated employing electron beam lithography. Diazonium modification was first developed on SiCN surfaces and validated by X-ray photoelectron spectroscopy. Similarly modified nanostrings were then covalently functionalized with anti rabbit IgG as a molecular probe. Specific enumeration of rabbit IgG was successfully performed through observation of downshifts of resonant frequencies. The specificity of this enumeration was confirmed through proper negative control experiments. Helium ion microscopy further verified the successful functionalization of nanostrings. PMID- 26263991 TI - Initial Results Obtained with the First TWIN VLBI Radio Telescope at the Geodetic Observatory Wettzell. AB - Geodetic Very Long Baseline Interferometry (VLBI) uses radio telescopes as sensor networks to determine Earth orientation parameters and baseline vectors between the telescopes. The TWIN Telescope Wettzell 1 (TTW1), the first of the new 13.2 m diameter telescope pair at the Geodetic Observatory Wettzell, Germany, is currently in its commissioning phase. The technology behind this radio telescope including the receiving system and the tri-band feed horn is depicted. Since VLBI telescopes must operate at least in pairs, the existing 20 m diameter Radio Telescope Wettzell (RTW) is used together with TTW1 for practical tests. In addition, selected long baseline setups are investigated. Correlation results portraying the data quality achieved during first initial experiments are discussed. Finally, the local 123 m baseline between the old RTW telescope and the new TTW1 is analyzed and compared with an existing high-precision local survey. Our initial results are very satisfactory for X-band group delays featuring a 3D distance agreement between VLBI data analysis and local ties of 1 to 2 mm in the majority of the experiments. However, S-band data, which suffer much from local radio interference due to WiFi and mobile communications, are about 10 times less precise than X-band data and require further analysis, but evidence is provided that S-band data are well-usable over long baselines where local radio interference patterns decorrelate. PMID- 26263992 TI - The Structure Design of Piezoelectric Poly(vinylidene Fluoride) (PVDF) Polymer Based Sensor Patch for the Respiration Monitoring under Dynamic Walking Conditions. AB - This study reports a piezoelectric poly(vinylidene fluoride) (PVDF) polymer-based sensor patch for respiration detections in dynamic walking condition. The working mechanism of respiration signal generation is based on the periodical deformations on a human chest wall during the respiratory movements, which in turn mechanically stretch the piezoelectric PVDF film to generate the corresponding electrical signals. In this study, the PVDF sensing film was completely encapsulated within the sensor patch forming a mass-spring-damper mechanical system to prevent the noises generated in a dynamic condition. To verify the design of sensor patch to prevent dynamic noises, experimental investigations were carried out. Results demonstrated the respiration signals generated and the respiratory rates measured by the proposed sensor patch were in line with the same measurements based on a commercial respiratory effort transducer both in a static (e.g., sitting) or dynamic (e.g., walking) condition. As a whole, this study has developed a PVDF-based sensor patch which is capable of monitoring respirations in a dynamic walking condition with high fidelity. Other distinctive features include its small size, light weight, ease of use, low cost, and portability. All these make it a promising sensing device to monitor respirations particularly in home care units. PMID- 26263994 TI - A Nano-Thin Film-Based Prototype QCM Sensor Array for Monitoring Human Breath and Respiratory Patterns. AB - Quartz crystal microbalance (QCM) sensor array was developed for multi-purpose human respiration assessment. The sensor system was designed to provide feedback for human respiration. Thorough optimization of measurement conditions: air flow, temperature in the QCM chamber, frequency measurement rate, and electrode position regarding to the gas flow-was performed. As shown, acquisition of respiratory parameters (rate and respiratory pattern) could be achieved even with a single electrode used in the system. The prototype system contains eight available QCM channels that can be potentially used for selective responses to certain breath chemicals. At present, the prototype machine is ready for the assessment of respiratory functions in larger populations in order to gain statistical validation. To the best of our knowledge, the developed prototype is the only respiratory assessment system based on surface modified QCM sensors. PMID- 26263993 TI - Upper Limb Kinematics Using Inertial and Magnetic Sensors: Comparison of Sensor to-Segment Calibrations. AB - Magneto-Inertial Measurement Unit sensors (MIMU) display high potential for the quantitative evaluation of upper limb kinematics, as they allow monitoring ambulatory measurements. The sensor-to-segment calibration step, consisting of establishing the relation between MIMU sensors and human segments, plays an important role in the global accuracy of joint angles. The aim of this study was to compare sensor-to-segment calibrations for the MIMU-based estimation of wrist, elbow, and shoulder joint angles, by examining trueness ("close to the reference") and precision (reproducibility) validity criteria. Ten subjects performed five sessions with three different operators. Three classes of calibrations were studied: segment axes equal to technical MIMU axes (TECH), segment axes generated during a static pose (STATIC), and those generated during functional movements (FUNCT). The calibrations were compared during the maximal uniaxial movements of each joint, plus an extra multi-joint movement. Generally, joint angles presented good trueness and very good precision in the range 5 degrees -10 degrees . Only small discrepancy between calibrations was highlighted, with the exception of a few cases. The very good overall accuracy (trueness and precision) of MIMU-based joint angle data seems to be more dependent on the level of rigor of the experimental procedure (operator training) than on the choice of calibration itself. PMID- 26263995 TI - Mechanical and Electrical Characterization of Piezoelectric Artificial Cochlear Device and Biocompatible Packaging. AB - This paper presents the development of a piezoelectric artificial cochlea (PAC) device capable of analyzing vibratory signal inputs and converting them into electrical signal outputs without an external power source by mimicking the function of human cochlea within an audible frequency range. The PAC consists of an artificial basilar membrane (ABM) part and an implantable packaged part. The packaged part provides a liquid environment through which incoming vibrations are transmitted to the membrane part. The membrane part responds to the transmitted signal, and the local area of the ABM part vibrates differently depending on its local resonant frequency. The membrane was designed to have a logarithmically varying width from 0.97 mm to 8.0 mm along the 28 mm length. By incorporating a micro-actuator in an experimental platform for the package part that mimics the function of a stapes bone in the middle ear, we created a similar experimental environment to cochlea where the human basilar membrane vibrates. The mechanical and electrical responses of fabricated PAC were measured with a laser Doppler vibrometer and a data acquisition system, and were compared with simulation results. Finally, the fabricated PAC in a biocompatible package was developed and its mechanical and electrical characteristics were measured. The experimental results shows successful frequency separation of incoming mechanical signal from micro-actuator into frequency bandwidth within the 0.4 kHz-5 kHz range. PMID- 26263996 TI - Optimal Atmospheric Correction for Above-Ground Forest Biomass Estimation with the ETM+ Remote Sensor. AB - The reflectance of the Earth's surface is significantly influenced by atmospheric conditions such as water vapor content and aerosols. Particularly, the absorption and scattering effects become stronger when the target features are non-bright objects, such as in aqueous or vegetated areas. For any remote-sensing approach, atmospheric correction is thus required to minimize those effects and to convert digital number (DN) values to surface reflectance. The main aim of this study was to test the three most popular atmospheric correction models, namely (1) Dark Object Subtraction (DOS); (2) Fast Line-of-sight Atmospheric Analysis of Spectral Hypercubes (FLAASH) and (3) the Second Simulation of Satellite Signal in the Solar Spectrum (6S) and compare them with Top of Atmospheric (TOA) reflectance. By using the k-Nearest Neighbor (kNN) algorithm, a series of experiments were conducted for above-ground forest biomass (AGB) estimations of the Gongju and Sejong region of South Korea, in order to check the effectiveness of atmospheric correction methods for Landsat ETM+. Overall, in the forest biomass estimation, the 6S model showed the bestRMSE's, followed by FLAASH, DOS and TOA. In addition, a significant improvement of RMSE by 6S was found with images when the study site had higher total water vapor and temperature levels. Moreover, we also tested the sensitivity of the atmospheric correction methods to each of the Landsat ETM+ bands. The results confirmed that 6S dominates the other methods, especially in the infrared wavelengths covering the pivotal bands for forest applications. Finally, we suggest that the 6S model, integrating water vapor and aerosol optical depth derived from MODIS products, is better suited for AGB estimation based on optical remote-sensing data, especially when using satellite images acquired in the summer during full canopy development. PMID- 26263997 TI - Development of a Novel, Low-Cost, Disposable Wooden Pencil Graphite Electrode for Use in the Determination of Antioxidants and Other Biological Compounds. AB - The development of portable sensors that can be used outside the lab is an active area of research in the electroanalytical field. A major focus of such research is the development of low-cost electrodes for use in these sensors. Current electrodes, such as glassy-carbon electrodes (GCEs), are costly and require time consuming preparation. Alternatives have been proposed, including mechanical pencil-lead electrodes (MPEs). However, MPEs themselves possess numerous drawbacks, particularly structural fragility. In this paper, we present a novel pencil-graphite electrode (PGE) fabricated from a regular HB#2 pencil. This PGE is a simple, disposable, extremely low-cost alternative to GCEs ($0.30 per PGE, vs. $190 + per GCE), and possesses the structural stability that MPEs lack. PGEs were characterized by square-wave voltammetry of ferricyanide, gallic acid, uric acid, dopamine, and several foodstuffs. In all cases, PGEs demonstrated sensitivities comparable or superior to those of the GCE and MPE (LOD = 5.62 * 10(-4) M PGE, 4.80 * 10(-4) M GCE, 2.93 * 10(-4) M MPE). Signal areas and peak heights were typically four to ten times larger for the PGE relative to the GCE. PMID- 26263998 TI - Tracking the Evolution of Smartphone Sensing for Monitoring Human Movement. AB - Advances in mobile technology have led to the emergence of the "smartphone", a new class of device with more advanced connectivity features that have quickly made it a constant presence in our lives. Smartphones are equipped with comparatively advanced computing capabilities, a global positioning system (GPS) receivers, and sensing capabilities (i.e., an inertial measurement unit (IMU) and more recently magnetometer and barometer) which can be found in wearable ambulatory monitors (WAMs). As a result, algorithms initially developed for WAMs that "count" steps (i.e., pedometers); gauge physical activity levels; indirectly estimate energy expenditure and monitor human movement can be utilised on the smartphone. These algorithms may enable clinicians to "close the loop" by prescribing timely interventions to improve or maintain wellbeing in populations who are at risk of falling or suffer from a chronic disease whose progression is linked to a reduction in movement and mobility. The ubiquitous nature of smartphone technology makes it the ideal platform from which human movement can be remotely monitored without the expense of purchasing, and inconvenience of using, a dedicated WAM. In this paper, an overview of the sensors that can be found in the smartphone are presented, followed by a summary of the developments in this field with an emphasis on the evolution of algorithms used to classify human movement. The limitations identified in the literature will be discussed, as well as suggestions about future research directions. PMID- 26263999 TI - On the Quest of Cellular Functions of PEA-15 and the Therapeutic Opportunities. AB - Phosphoprotein enriched in astrocytes, 15 KDa (PEA-15), a ubiquitously expressed small protein in all mammals, is known for decades for its potent interactions with various protein partners along distinct biological pathways. Most notable interacting partners of PEA-15 include extracellular signal-regulated kinase 1 and 2 (ERK1/2) in the mitogen activated protein kinase (MAPK) pathway, the Fas associated death domain (FADD) protein involving in the formation of the death inducing signaling complex (DISC), and the phospholipase D1 (PLD1) affecting the insulin sensitivity. However, the actual cellular functions of PEA-15 are still mysterious, and the question why this protein is expressed in almost all cell and tissue types remains unanswered. Here we synthesize the most recent structural, biological, and clinical studies on PEA-15 with emphases on its anti-apoptotic, anti-proliferative, and anti-inflammative properties, and propose a converged protective role of PEA-15 that maintains the balance of death and survival in different cell types. Under conditions that this delicate balance is unsustainable, PEA-15 may become pathological and lead to various diseases, including cancers and diabetes. Targeting PEA-15 interactions, or the use of PEA 15 protein as therapeutics, may provide a wider window of opportunities to treat these diseases. PMID- 26264000 TI - Temperature-Dependence of Lipid A Acyl Structure in Psychrobacter cryohalolentis and Arctic Isolates of Colwellia hornerae and Colwellia piezophila. AB - Lipid A is a fundamental Gram-negative outer membrane component and the essential element of lipopolysaccharide (endotoxin), a potent immunostimulatory molecule. This work describes the metabolic adaptation of the lipid A acyl structure by Psychrobacter cryohalolentis at various temperatures in its facultative psychrophilic growth range, as characterized by MALDI-TOF MS and FAME GC-MS. It also presents the first elucidation of lipid A structure from the Colwellia genus, describing lipid A from strains of Colwellia hornerae and Colwellia piezophila, which were isolated as primary cultures from Arctic fast sea ice and identified by 16S rDNA sequencing. The Colwellia strains are obligate psychrophiles, with a growth range restricted to 15 degrees C or less. As such, these organisms have less need for fluidity adaptation in the acyl moiety of the outer membrane, and they do not display alterations in lipid A based on growth temperature. Both Psychrobacter and Colwellia make use of extensive single methylene variation in the size of their lipid A molecules. Such single-carbon variations in acyl size were thought to be restricted to psychrotolerant (facultative) species, but its presence in these Colwellia species shows that odd chain acyl units and a single-carbon variation in lipid A structure are present in obligate psychrophiles, as well. PMID- 26264001 TI - Nrf2 and NF-kappaB Signaling Pathways Contribute to Porphyra-334-Mediated Inhibition of UVA-Induced Inflammation in Skin Fibroblasts. AB - In this study, we examined the protective effects of porphyra-334 against UVA irradiated cellular damage and elucidated the underlying mechanisms. Porphyra-334 prevented UVA-induced cell death and exhibited scavenging activities against intracellular oxidative stress induced by UVA irradiation in skin fibroblasts. We found that porphyra-334 significantly reduced the secretion and expression of IL 6 and TNF-alpha, reduced nuclear expression of Nuclear factor-kappaB (NF-kappaB), and sustained NF-E2-related factor 2 (Nrf2) activation. Further mechanism research revealed that porphyra-334 promoted the Nrf2 signaling pathway in UVA irradiated skin fibroblasts. Our results show that the antioxidant effect of porphyra-334 is due to the direct scavenging of oxidative stress and its inhibitory effects on NF-kappaB-dependent inflammatory genes, such as IL-6 and TNF-kappa. Therefore, we hypothesize that boosting the Nrf2- NF-kappaB-dependent response to counteract environmental stress is a promising strategy for the prevention of UVA-related damage. PMID- 26264002 TI - Antitumor Effects and Related Mechanisms of Penicitrinine A, a Novel Alkaloid with a Unique Spiro Skeleton from the Marine Fungus Penicillium citrinum. AB - Penicitrinine A, a novel alkaloid with a unique spiro skeleton, was isolated from a marine-derived fungus Penicillium citrinum. In this study, the isolation, structure and biosynthetic pathway elucidation of the new compound were described. This new compound showed anti-proliferative activity on multiple tumor types. Among them, the human malignant melanoma cell A-375 was confirmed to be the most sensitive. Morphologic evaluation, apoptosis rate analysis, Western blot and real-time quantitative PCR (RT-qPCR) results showed penicitrinine A could significantly induce A-375 cell apoptosis by decreasing the expression of Bcl-2 and increasing the expression of Bax. Moreover, we investigated the anti metastatic effects of penicitrinine A in A-375 cells by wound healing assay, trans-well assay, Western blot and RT-qPCR. The results showed penicitrinine A significantly suppressed metastatic activity of A-375 cells by regulating the expression of MMP-9 and its specific inhibitor TIMP-1. These findings suggested that penicitrinine A might serve as a potential antitumor agent, which could inhibit the proliferation and metastasis of tumor cells. PMID- 26264003 TI - The Sound of Silence: Activating Silent Biosynthetic Gene Clusters in Marine Microorganisms. AB - Unlocking the rich harvest of marine microbial ecosystems has the potential to both safeguard the existence of our species for the future, while also presenting significant lifestyle benefits for commercial gain. However, while significant advances have been made in the field of marine biodiscovery, leading to the introduction of new classes of therapeutics for clinical medicine, cosmetics and industrial products, much of what this natural ecosystem has to offer is locked in, and essentially hidden from our screening methods. Releasing this silent potential represents a significant technological challenge, the key to which is a comprehensive understanding of what controls these systems. Heterologous expression systems have been successful in awakening a number of these cryptic marine biosynthetic gene clusters (BGCs). However, this approach is limited by the typically large size of the encoding sequences. More recently, focus has shifted to the regulatory proteins associated with each BGC, many of which are signal responsive raising the possibility of exogenous activation. Abundant among these are the LysR-type family of transcriptional regulators, which are known to control production of microbial aromatic systems. Although the environmental signals that activate these regulatory systems remain unknown, it offers the exciting possibility of evoking mimic molecules and synthetic expression systems to drive production of potentially novel natural products in microorganisms. Success in this field has the potential to provide a quantum leap forward in medical and industrial bio-product development. To achieve these new endpoints, it is clear that the integrated efforts of bioinformaticians and natural product chemists will be required as we strive to uncover new and potentially unique structures from silent or cryptic marine gene clusters. PMID- 26264005 TI - School Term vs. School Holiday: Associations with Children's Physical Activity, Screen-Time, Diet and Sleep. AB - This cross-sectional study examined differences in children's health behaviors during school term (ST) versus school holiday (SH: June-July) and how associations changed when weather characteristics were considered. Children aged 5-18 years (n = 406) from a subtropical climate reported behaviors over 20 months. Multivariable regression models controlling for age, sex, race and body mass index z-score (BMIz) were used to examine associations between SH and each behavior. A second model included heat index, precipitation and daylight hours. Strenuous activity, moderate activity, total activity and TV viewing were significantly higher during SH than ST. After adjusting for weather characteristics, total activity remained significantly higher during SH, but the association with TV viewing was attenuated. Youth surveyed during high precipitation were significantly less likely to meet physical activity guidelines. There were no significant associations between SH and meeting sleep, physical activity or screen-time guidelines. Weather characteristics influenced associations between SH and youth's physical activity and TV viewing. PMID- 26264004 TI - Fucoxanthin and Its Metabolite Fucoxanthinol in Cancer Prevention and Treatment. AB - Fucoxanthin is a carotenoid present in the chloroplasts of brown seaweeds. When ingested, it is metabolized mainly to fucoxanthinol by digestive enzymes of the gastrointestinal tract. These compounds have been shown to have many beneficial health effects, including anti-mutagenic, anti-diabetic, anti-obesity, anti inflammatory and anti-neoplastic actions. In every cancer tested, modulatory actions of fucoxanthinol on viability, cell-cycle arrest, apoptosis and members of the NF-kappaB pathway were more pronounced than that of fucoxanthin. Anti proliferative and cancer preventing influences of fucoxanthin and fucoxanthinol are mediated through different signalling pathways, including the caspases, Bcl-2 proteins, MAPK, PI3K/Akt, JAK/STAT, AP-1, GADD45, and several other molecules that are involved in cell cycle arrest, apoptosis, anti-angiogenesis or inhibition of metastasis. In this review, we address the mechanisms of action of fucoxanthin and fucoxanthinol according to different types of cancers. Current findings suggest that these compounds could be effective for treatment and/or prevention of cancer development and aggressiveness. PMID- 26264006 TI - Infection Control Programs and Antibiotic Control Programs to Limit Transmission of Multi-Drug Resistant Acinetobacter baumannii Infections: Evolution of Old Problems and New Challenges for Institutes. AB - BACKGROUND: Acinetobacter baumannii complex (A. baumannii) has been isolated worldwide. The rapid spread of multidrug-resistant A. baumannii complex (MDRAB) in clinical settings has made choosing an appropriate antibiotic to treat these infections and executing contact precautions difficult for clinicians. Although controlling the transmission of MDRAB is a high priority for institutions, there is little information about MDRAB control. Therefore, this study evaluated infection control measures for A. baumannii infections, clusters and outbreaks in the literature. METHODS: We performed a review of OVID Medline (from 1980 to 2015), and analyzed the literature. RESULTS: We propose that both infection control programs and antibiotic control programs are essential for control of MDRAB. The first, effective control of MDRAB infections, requires compliance with a series of infection control methods including strict environmental cleaning, effective sterilization of reusable medical equipment, concentration on proper hand hygiene practices, and use of contact precautions, together with appropriate administrative guidance. The second strategy, effective antibiotic control programs to decrease A. baumannii, is also of paramount importance. CONCLUSION: We believe that both infection control programs and antibiotics stewardship programs are essential for control of MDRAB infections. PMID- 26264007 TI - Effects of Individual and School-Level Characteristics on a Child's Gross Motor Coordination Development. AB - The aim of this study was to identify child and school-level characteristics that explained inter-individual differences in gross motor coordination (GMC). Participants (n = 390), recruited from 18 Portuguese primary schools, were aged 6 to 10 years of age. Birth weight, body fat (BF), physical activity (PA), physical fitness (PF) and GMC were assessed. School size, setting, infrastructure and physical education classes were considered as school context markers. A multilevel modeling approach was used to identify hierarchical effects (child and school levels). It was found that children-level variables (sex, PF, and BF) significantly explained 63% of the 90% variance fraction at the individual level; boys outperformed girls (p < 0.05), individuals with higher BF were less coordinated (p < 0.05), and those with higher PF were more coordinated (p < 0.05). School-variables (e.g. school size and playing surface) explained 84% of the 10% variation fraction. These findings confirm the roles of sex, PFS and BF. Interestingly they also suggest that the school environment plays a minor but significant role in GMC development. However, it is important to stress that the school context and conditions can also play an important role in a child's motor development, providing adequate and enriching motor opportunities. PMID- 26264008 TI - Surrogate Model Application to the Identification of Optimal Groundwater Exploitation Scheme Based on Regression Kriging Method-A Case Study of Western Jilin Province. AB - This paper introduces a surrogate model to identify an optimal exploitation scheme, while the western Jilin province was selected as the study area. A numerical simulation model of groundwater flow was established first, and four exploitation wells were set in the Tongyu county and Qian Gorlos county respectively so as to supply water to Daan county. Second, the Latin Hypercube Sampling (LHS) method was used to collect data in the feasible region for input variables. A surrogate model of the numerical simulation model of groundwater flow was developed using the regression kriging method. An optimization model was established to search an optimal groundwater exploitation scheme using the minimum average drawdown of groundwater table and the minimum cost of groundwater exploitation as multi-objective functions. Finally, the surrogate model was invoked by the optimization model in the process of solving the optimization problem. Results show that the relative error and root mean square error of the groundwater table drawdown between the simulation model and the surrogate model for 10 validation samples are both lower than 5%, which is a high approximation accuracy. The contrast between the surrogate-based simulation optimization model and the conventional simulation optimization model for solving the same optimization problem, shows the former only needs 5.5 hours, and the latter needs 25 days. The above results indicate that the surrogate model developed in this study could not only considerably reduce the computational burden of the simulation optimization process, but also maintain high computational accuracy. This can thus provide an effective method for identifying an optimal groundwater exploitation scheme quickly and accurately. PMID- 26264009 TI - Chronic Exposure to Static Magnetic Fields from Magnetic Resonance Imaging Devices Deserves Screening for Osteoporosis and Vitamin D Levels: A Rat Model. AB - Technicians often receive chronic magnetic exposures from magnetic resonance imaging (MRI) devices, mainly due to static magnetic fields (SMFs). Here, we ascertain the biological effects of chronic exposure to SMFs from MRI devices on the bone quality using rats exposed to SMFs in MRI examining rooms. Eighteen Wistar albino male rats were randomly assigned to SMF exposure (A), sham (B), and control (C) groups. Group A rats were positioned within 50 centimeters of the bore of the magnet of 1.5 T MRI machine during the nighttime for 8 weeks. We collected blood samples for biochemical analysis, and bone tissue samples for electron microscopic and histological analysis. The mean vitamin D level in Group A was lower than in the other groups (p = 0.002). The mean cortical thickness, the mean trabecular wall thickness, and number of trabeculae per 1 mm2 were significantly lower in Group A (p = 0.003). TUNEL assay revealed that apoptosis of osteocytes were significantly greater in Group A than the other groups (p = 0.005). The effect of SMFs in chronic exposure is related to movement within the magnetic field that induces low-frequency fields within the tissues. These fields can exceed the exposure limits necessary to deteriorate bone microstructure and vitamin D metabolism. PMID- 26264010 TI - A Comparative Analyses of Granulometry, Mineral Composition and Major and Trace Element Concentrations in Soils Commonly Ingested by Humans. AB - This study compared the granulometric properties, mineralogical composition and concentrations of major and trace element oxides of commonly ingested soils (geophagic soil) collected from different countries with a view of understanding how varied they may be in these properties and to understand the possible health implications of ingesting them. Soil samples were collected from three different countries (South Africa, Swaziland and Democratic Republic of Congo (DRC)) and their granulometric properties, concentrations of major and trace element oxides as well as mineralogical composition determined. Differences were observed in the granulometric properties of geophagic soil from the three different countries with most of them having <20% clay content. The soils also showed varied degrees of weathering with values of Chemical Index of Alteration (CIA) and Chemical Index of Weathering (CIW) being between 60% and 99.9% respectively. The mineral assemblages of the soils from South Africa and Swaziland were dominated by the primary minerals quartz and feldspar whereas soils from DRC had more of kaolinite, a secondary mineral than primary minerals. Soils from DRC were associated with silt, clay, Al2O3, and CIA unlike most samples from South Africa which were associated with SiO2, sand, K2O, CaO, and MgO. The soils from Swaziland were closely associated with silt, H2O and Fe2O3(t). These associations reflect the mineralogy of the samples. These soils are not likely to serve as nutrient supplements because of the low concentrations of the nutrient elements contained. The coarse texture of the samples may also result in dental destruction during mastication. Sieving of the soils before ingestion to remove coarse particles is recommended to reduce the potential health threat associated with the ingestion of coarse-textured soils. PMID- 26264011 TI - Perspectives on Smoking Initiation and Maintenance: A Qualitative Exploration among Singapore Youth. AB - Studies among adolescents have shown that several important interpersonal, intrapersonal and environmental factors are associated with smoking behaviour. The current qualitative research project aimed to explore the determinants of smoking initiation and maintenance, from a youth perspective, among young people who smoked, living in a multi-ethnic Asian country. Focus group discussions (FGDs) were conducted with youths in Singapore in youth-friendly and accessible locations. Young people, from a variety of social contexts-varying on age, gender, ethnicity and educational level, were included in the study. All FGDs were conducted in English and participants were recruited using a mix of network and purposive sampling. All FGDs were audio recorded and transcribed verbatim. The data were analyzed using qualitative content analysis, allowing themes to emerge from the data with the goal of answering the research question. Ninety-one youth smokers (54 males, 37 females), aged between 14 to 29 years, participated in the study. The majority were males (59%) and of Chinese ethnicity (52%). Participants identified multiple personal, social, and familial influences on young adults' smoking behaviors. Peer and family influences, as well as risk minimization, played a key role in smoking initiation and maintenance. While young people were aware of policies that restricted smoking, these did not directly affect their decision to start smoking. The theory of triadic influence provided a promising theoretical framework to understand smoking initiation and maintenance in a sample of young adult smokers from a multi-ethnic Asian country. It also provides actionable information for initiatives to prevent smoking in young people, which includes their perspectives and emphasizes an inclusive approach without stigmatizing those who smoke. PMID- 26264013 TI - Urbanization and Mental Health in China: Linking the 2010 Population Census with a Cross-Sectional Survey. AB - Along with the rapid urbanization in China, the state of mental health also receives growing attention. Empirical measures, however, have not been developed to assess the impact of urbanization on mental health and the dramatic spatial variations. Innovatively linking the 2010 Chinese Population Census with a 2011 national survey of urban residents, we first assess the impact of urbanization on depressive symptoms measured by the Center of Epidemiological Studies Depression Scale (CES-D) of 1288 survey respondents. We then retrieve county-level characteristics from the 2010 Chinese Population Census that match the individual characteristics in the survey, so as to create a profile of the "average person" for each of the 2869 counties or city districts, and predict a county-specific CES-D score. We use this county-specific CES-D score to compute the CES-D score for the urban population at the prefectural level, and to demonstrate the dramatic spatial variations in urbanization and mental health across China: highly populated cities along the eastern coast such as Shenyang and Shanghai show high CES-D scores, as do cities in western China with high population density and a high proportion of educated ethnic minorities. PMID- 26264012 TI - Integrated Assessment of Artisanal and Small-Scale Gold Mining in Ghana-Part 2: Natural Sciences Review. AB - This paper is one of three synthesis documents produced via an integrated assessment (IA) that aims to increase understanding of artisanal and small-scale gold mining (ASGM) in Ghana. Given the complexities surrounding ASGM, an integrated assessment (IA) framework was utilized to analyze socio-economic, health, and environmental data, and co-develop evidence-based responses with stakeholders. This paper focuses on the causes, status, trends, and consequences of ecological issues related to ASGM activity in Ghana. It reviews dozens of studies and thousands of samples to document evidence of heavy metals contamination in ecological media across Ghana. Soil and water mercury concentrations were generally lower than guideline values, but sediment mercury concentrations surpassed guideline values in 64% of samples. Arsenic, cadmium, and lead exceeded guideline values in 67%, 17%, and 24% of water samples, respectively. Other water quality parameters near ASGM sites show impairment, with some samples exceeding guidelines for acidity, turbidity, and nitrates. Additional ASGM-related stressors on environmental quality and ecosystem services include deforestation, land degradation, biodiversity loss, legacy contamination, and potential linkages to climate change. Though more research is needed to further elucidate the long-term impacts of ASGM on the environment, the plausible consequences of ecological damages should guide policies and actions to address the unique challenges posed by ASGM. PMID- 26264014 TI - Residence in Proximity of an Iron Foundry and Risk of Lung Cancer in the Municipality of Trieste, Italy, 1995-2009. AB - We assessed the risk of lung cancer in people living near the iron foundry located within the city of Trieste, Northeastern Italy. Between 1995 and 2009, all incident cases of lung cancer and corresponding population were considered. A deposition model of the foundry-specific emissions of SO2 defined: "nearby", "urban", and "outlying" areas. Rate ratios (RRs) and annual percent changes (APCs) were computed. Among nearby residents, significantly increased risks of lung cancer were noted in men below age 75 years (RR = 1.35 vs. urban area; 95% CI: 1.03-1.77). In women, and in men aged 75 years or older, no significant RRs were observed. Conversely, people living in the outlying area appeared to be at lower risk than residents in the urban area- in all age groups, in men (RR = 0.87; 95% CI: 0.78-0.98) and in women (RR = 0.74; 95% CI: 0.62-0.88). Negative statistically significant APC was recorded in men living in urban areas (-2.6%), whereas in women APC significantly increased among those living in the urban area (+2.3%). Multiple interpretations for this observation are plausible, since several factors might have modified and/or confounded the risk of lung cancer, including air pollution from other sources and road traffic, occupational and smoking patterns. PMID- 26264015 TI - Prevalence and Determinants of Anemia and Iron Deficiency in Kuwait. AB - The objective of this study was to assess the prevalence of anemia and iron deficiency (ID) of a nationally representative sample of the Kuwait population. We also determined if anemia differed by socioeconomic status or by RBC folate and vitamins A and B12 levels. The subjects who were made up of 1830 males and females between the ages of 2 months to 86 years, were divided into the following age groups (0-5, 5-11, 12-14, 15-19, 20-49, >=50 years). Results showed that the prevalence of anemia was 3% in adult males and 17% in females. The prevalence of ID varied according to age between 4% (>=50 years) and 21% (5-11 years) and 9% (12-14 years) and 23% (15-19 years), respectively, in males and females. The prevalence of anemia and ID was higher in females compared to males. Adults with normal ferritin level, but with low RBC folate and vitamins A and B12 levels had higher prevalence of anemia than those with normal RBC folate and vitamins A and B12 levels. This first nationally representative nutrition and health survey in Kuwait indicated that anemia and ID are prevalent and ID contributes significantly to anemia prevalence. PMID- 26264016 TI - Tobacco-Specific Nitrosamines in Electronic Cigarettes: Comparison between Liquid and Aerosol Levels. AB - INTRODUCTION: Although electronic cigarette (EC) liquids contain low levels of tobacco-specific nitrosamines (TSNAs), studies evaluating the levels emitted to the aerosol are scarce. The purpose of this study was to compare the levels of TSNAs between liquids and generated aerosol. METHODS: Three EC liquids were obtained from the market. An additional (spiked) sample was prepared by adding known amounts of standard TSNAs solutions to one of the obtained liquids. N nitrosonornicotine (NNN), N-nitrosoanatabine (NAT), N-nitrosoanabasine (NAB) and 4-(methylnitrosamino)1-(3-pyridyl)-1-butanone (NNK) were measured. Three 100-puff sets from each liquid were trapped in filter pads and were subsequently analyzed for the presence of TSNAs. The expected levels of TSNAs (calculated based on the liquid consumption) were compared with the measured levels in the aerosol. RESULTS: Only NAB was found at trace levels in two commercial liquids (1.2 and 2.3 ng/g), while the third contained 1.5 ng/g NAB and 7.7 ng/g NNN. The 100-puff sets resulted in 336-515 mg liquid consumption, with no TSNAs being detected in the aerosol. The spiked sample contained 42.0-53.9 ng/g of each of the TSNAs. All TSNAs were detected in the aerosol with the measured levels being statistically similar to the expected amounts. A significant correlation between expected and measured levels of TSNAs in the aerosol was found (r = 0.83, p < 0.001). CONCLUSION: The findings of this study show that exposure of EC users to TSNAs can be accurately assessed based on the levels present in the liquid, without the need to analyze the aerosol. PMID- 26264017 TI - Estimation of the Biological Half-Life of Methylmercury Using a Population Toxicokinetic Model. AB - Methylmercury is well known for causing adverse health effects in the brain and nervous system. Estimating the elimination constant derived from the biological half-life of methylmercury in the blood or hair is an important part of calculating guidelines for methylmercury intake. Thus, this study was conducted to estimate the biological half-life of methylmercury in Korean adults. We used a one-compartment model with a direct relationship between methylmercury concentrations in the blood and daily dietary intake of methylmercury. We quantified the between-person variability of the methylmercury half-life in the population, and informative priors were used to estimate the parameters in the model. The population half-life of methylmercury was estimated to be 80.2 +/- 8.6 days. The population mean of the methylmercury half-life was 81.6 +/- 8.4 days for men and 78.9 +/- 8.6 days for women. The standard deviation of the half-life was estimated at 25.0 +/- 8.6 days. Using the direct relationship between methylmercury concentrations in blood and methylmercury intake, the biological half-life in this study was estimated to be longer than indicated by the earlier studies that have been used to set guideline values. PMID- 26264018 TI - Short-Term Effect of Ambient Temperature and the Risk of Stroke: A Systematic Review and Meta-Analysis. AB - BACKGROUND AND PURPOSE: The relationship between stroke and short-term temperature changes remains controversial. Therefore, we conducted a systematic review and meta-analysis to investigate the association between stroke and both high and low temperatures, and health assessment. METHODS: We searched PubMed, Embase, Cochrane, China National Knowledge Infrastructure (CNKI) and Wanfang Data up to 14 September 2014. Study selection, quality assessment, and author contractions were steps before data extraction. We converted all estimates effects into relative risk (RR) per 1 degrees C increase/decrease in temperature from 75th to 99th or 25th to 1st percentiles, then conducted meta-analyses to combine the ultimate RRs, and assessed health impact among the population. RESULTS: 20 articles were included in the final analysis. The overall analysis showed a positive relationship between 1 degrees C change and the occurrence of major adverse cerebrovascular events (MACBE), 1.1% (95% confidence intervals (CI), 0.6 to 1.7) and 1.2% (95% CI, 0.8 to 1.6) increase for hot and cold effects separately. The same trends can be found in both effects of mortality and the cold effect for morbidity. Hot temperature acted as a protective factor of hemorrhage stroke (HS), -1.9% (95% CI, -2.8 to -0.9), however, it acted as a risk factor for ischemic stroke (IS), 1.2% (95% CI, 0.7 to 1.8). CONCLUSION: Short term changes of both low and high temperature had statistically significant impacts on MACBE. PMID- 26264019 TI - Matrix Metalloproteinase-9 Mediates RSV Infection in Vitro and in Vivo. AB - Respiratory Syncytial Virus (RSV) is an important human pathogen associated with substantial morbidity and mortality. The present study tested the hypothesis that RSV infection would increase matrix metalloproteinase (MMP)-9 expression, and that MMP-9 inhibition would decrease RSV replication both in vitro and in vivo. RSV A2 infection of human bronchial epithelial cells increased MMP-9 mRNA and protein release. Cells transfected with siRNA against MMP-9 following RSV infection had lower viral titers. In RSV infected wild-type (WT) mice, MMP-9, airway resistance and viral load peaked at day 2 post infection, and remained elevated on days 4 and 7. RSV infected MMP-9 knockout (KO) mice had decreased lung inflammation. On days 2 and 4 post inoculation, the RSV burden was lower in the MMP-9 KO mice compared to WT controls. In conclusion, our studies demonstrate that RSV infection is a potent stimulus of MMP-9 expression both in vitro and in vivo. Reduction of MMP-9 (via siRNA knockdown, and in MMP-9 KO mice) resulted in decreased viral replication. Our findings suggest MMP-9 is a potential therapeutic target for RSV disease. PMID- 26264020 TI - Public Acceptance of Plant Biotechnology and GM Crops. AB - A wide gap exists between the rapid acceptance of genetically modified (GM) crops for cultivation by farmers in many countries and in the global markets for food and feed, and the often-limited acceptance by consumers. This review contrasts the advances of practical applications of agricultural biotechnology with the divergent paths-also affecting the development of virus resistant transgenic crops-of political and regulatory frameworks for GM crops and food in different parts of the world. These have also shaped the different opinions of consumers. Important factors influencing consumer's attitudes are the perception of risks and benefits, knowledge and trust, and personal values. Recent political and societal developments show a hardening of the negative environment for agricultural biotechnology in Europe, a growing discussion-including calls for labeling of GM food-in the USA, and a careful development in China towards a possible authorization of GM rice that takes the societal discussions into account. New breeding techniques address some consumers' concerns with transgenic crops, but it is not clear yet how consumers' attitudes towards them will develop. Discussions about agriculture would be more productive, if they would focus less on technologies, but on common aims and underlying values. PMID- 26264021 TI - VKORC1 and VKORC1L1: Why do Vertebrates Have Two Vitamin K 2,3-Epoxide Reductases? AB - Among all cellular life on earth, with the exception of yeasts, fungi, and some prokaryotes, VKOR family homologs are ubiquitously encoded in nuclear genomes, suggesting ancient and important biological roles for these enzymes. Despite single gene and whole genome duplications on the largest evolutionary timescales, and the fact that most gene duplications eventually result in loss of one copy, it is surprising that all jawed vertebrates (gnathostomes) have retained two paralogous VKOR genes. Both VKOR paralogs function as entry points for nutritionally acquired and recycled K vitamers in the vitamin K cycle. Here we present phylogenetic evidence that the human paralogs likely arose earlier than gnathostomes, possibly in the ancestor of crown chordates. We ask why gnathostomes have maintained these paralogs throughout evolution and present a current summary of what we know. In particular, we look to published studies about tissue- and developmental stage-specific expression, enzymatic function, phylogeny, biological roles and associated pathways that together suggest subfunctionalization as a major influence in evolutionary fixation of both paralogs. Additionally, we investigate on what evolutionary timescale the paralogs arose and under what circumstances in order to gain insight into the biological raison d'etre for both VKOR paralogs in gnathostomes. PMID- 26264022 TI - O'Leary-Sant Symptom Index Predicts the Treatment Outcome for OnabotulinumtoxinA Injections for Refractory Interstitial Cystitis/Bladder Pain Syndrome. AB - Although intravesical injection of onabotulinumtoxinA (BoNT-A) has been proved promising in treating patients with interstitial cystitis/bladder pain syndrome (IC/BPS), what kind of patients that may benefit from this treatment remains unclear. This study investigated the predictors for a successful treatment outcome. Patients with IC/BPS who failed conventional treatments were enrolled to receive intravesical injection of 100 U of BoNT-A immediately followed by hydrodistention. Variables such as O'Leary-Sant symptom and problem indexes (ICSI and ICPI), pain visual analogue scale (VAS), functional bladder capacity (FBC), voiding diary, and urodynamic parameters were measured at baseline and six months after treatment. A global response assessment (GRA) >= 2 at six months was defined as successful. There were101 patients enrolled. Significant improvements were observed in mean ICSI, ICPI, OSS (ICSI + ICPI), pain VAS, FBC, frequency, nocturia and GRA at six months after BoNT-A injections (all p < 0.05). The successful rate at six months was 46/101 (45.54%). Multivariate logistic regression revealed the baseline ICSI (odds ratio = 0.770, 95% confidence interval = 0.601-0.989) was the only predictor for a treatment outcome. ICSI >= 12 was the most predictive cutoff value for a treatment failure, with a ROC area of 0.70 (sensitivity = 69.1%, specificity = 60.9%). PMID- 26264023 TI - Partial Characterization of Venom from the Colombian Spider Phoneutria Boliviensis (Aranae:Ctenidae). AB - We report on the first studies on the characterization of venom from Phoneutria boliviensis (Aranae:Ctenidae) (F. O. Pickard-Cambridge, 1897), done with Colombian species. After the electrostimulation extraction process, the venom showed physicochemical properties corresponding to a colorless and water-soluble liquid with a density of 0.86 mg/mL and 87% aqueous content. P. boliviensis venom and RP-HPLC fractions showed hemolytic activity and hydrolyzed the synthetic substrate 4-nitro-3-octanoyloxy-benzoic acid, indicating the presence of phospholipases A2 enzymes. The electrophoretic profile showed an important protein content with molecular masses below 14 kDa, and differences between male and female protein content were also revealed. The RP-HPLC venom profile exposes differences between males and female content consistent with the electrophoretic profile. Five fractions collected from the RP-HPLC displayed significant larvicidal activity. Mass analysis indicates the presence of peptides ranging from 1047.71 to 3278.07 Da. Two peptides, Ctenitoxin-Pb48 and Ctenitoxin-Pb53, were partially identified using HPLC-nESI-MS/MS, which showed a high homology with other Ctenitoxins (family Tx3) from Phoneutria nigriventer, Phoneutria keyserlingi and Phoneutria reidyi affecting voltage-gated calcium receptors (Cav 1, 2.1, 2.2 and 2.3) and NMDA-glutamate receptors. PMID- 26264024 TI - Dosimetric Characteristics of a Two-Dimensional Diode Array Detector Irradiated with Passively Scattered Proton Beams. AB - PURPOSE: To evaluate the dosimetric characteristics of a two-dimensional (2D) diode array detector irradiated with passively scattered proton beams. MATERIALS AND METHODS: A diode array detector, MapCHECK (Model 1175, Sun Nuclear, Melbourne, FL, USA) was characterized in passive-scattered proton beams. The relative sensitivity of the diodes and absolute dose calibration were determined using a 250 MeV beam. The pristine Bragg curves (PBCs) measured by MapCHECK diodes were compared with those of an ion chamber using a range shift method. The water-equivalent thickness (WET) of the diode array detector's intrinsic buildup also was determined. The inverse square dependence, linearity, and other proton dosimetric quantities measured by MapCHECK were also compared with those of the ion chambers. The change in the absolute dose response of the MapCHECK as a function of accumulated radiation dose was used as an indicator of radiation damage to the diodes. 2D dose distribution with and without the compensator were measured and compared with the treatment planning system (TPS) calculations. RESULTS: The WET of the MapCHECK diode's buildup was determined to be 1.7 cm. The MapCHECK-measured PBC were virtually identical to those measured by a parallel plate ion chamber for 160, 180, and 250 MeV proton beams. The inverse square results of the MapCHECK were within +/-0.4% of the ion chamber results. The linearity of MapCHECK results was within 1% of those from the ion chamber as measured in the range between 10 and 300 MU. All other dosimetric quantities were within 1.3% of the ion chamber results. The 2D dose distributions for non clinical fields without compensator and the patient treatment fields with the compensator were consistent with the TPS results. The absolute dose response of the MapCHECK was changed by 7.4% after an accumulated dose increased by 170 Gy. CONCLUSIONS: The MapCHECK is a convenient and useful tool for 2D dose distribution measurements using passively scattered proton beams. Variations in MapCHECK's dose response with increasing levels of total accumulated radiation dose should be carefully monitored. PMID- 26264025 TI - Role of the Aryl Hydrocarbon Receptor in Colon Neoplasia. AB - For both men and women, colorectal cancer (CRC) is the second leading cause of cancer death in the United States, primarily as a consequence of limited therapies for metastatic disease. The aryl hydrocarbon receptor (AhR) is a ligand dependent transcription factor with diverse functions in detoxification of xenobiotics, inflammatory responses, and tissue homeostasis. Emerging evidence indicates that AhR also plays an important role in regulating intestinal cell proliferation and tumorigenesis. Here, we review both the pro- and anti carcinogenic properties of AhR signaling and its potential role as a therapeutic target in CRC. PMID- 26264027 TI - Breast Cancer in Elderly Caucasian Women-An Institution-Based Study of Correlation between Breast Cancer Prognostic Markers, TNM Stage, and Overall Survival. AB - There is still a paucity of data on how breast cancer (BC) biology influences outcomes in elderly patients. We evaluated whether ER/PR/HER2 subtype and TNM stage of invasive BC had a significant impact on overall survival (OS) in a cohort of 232 elderly Caucasian female patients (>=70 year old (y/o)) from our institution over a ten-year interval (January 1998-July 2008). Five ER/PR/HER2 BC subtypes classified per 2011 St. Gallen International Expert Consensus recommendations were further subclassified into three subtypes (traditionally considered "favorable" subtype-ER+/PR+/HER2-, and traditionally considered "unfavorable" BC subtypes: HER2+ and triple negative). OS was measured comparing these categories using Kaplan Meier curves and Cox regression analysis, when controlled for TNM stage. The majority of our patients (178/232 = 76.8%) were of the "favorable" BC subtype; 23.2% patients were with "unfavorable" subtype (HER2+ = 12% (28/232) and triple negative = 11.2% (26/232)). Although a trend for better OS was noted in HER2+ patients (68%) vs. 56% in ER+/PR+ HER2- or 58% in triple negative patients, "favorable" BC subtype was not significantly predictive of better OS (p = 0.285). TNM stage was predictive of OS (p < 0.001). These results are similar to our published studies on Caucasian BC patients of all ages in which ER/PR/HER2 status was not predictive of OS, irrespective of classification system used. PMID- 26264026 TI - The Role of nAChR and Calcium Signaling in Pancreatic Cancer Initiation and Progression. AB - Pancreatic cancer shows a strong correlation with smoking and the current therapeutic strategies have been relatively ineffective in improving the survival of patients. Efforts have been made over the past many years to understand the molecular events that drive the initiation and progression of pancreatic cancer, especially in the context of smoking. It has become clear that components of tobacco smoke not only initiate these cancers, especially pancreatic ductal adenocarcinomas (PDACs) through their mutagenic properties, but can also promote the growth and metastasis of these tumors by stimulating cell proliferation, angiogenesis, invasion and epithelial-mesenchymal transition. Studies in cell culture systems, animal models and human samples have shown that nicotinic acetylcholine receptor (nAChR) activation enhances these tumor-promoting events by channeling signaling through multiple pathways. In this context, signaling through calcium channels appear to facilitate pancreatic cancer growth by itself or downstream of nAChRs. This review article highlights the role of nAChR downstream signaling events and calcium signaling in the growth, metastasis as well as drug resistance of pancreatic cancer. PMID- 26264028 TI - Cyclic GMP and Cilia Motility. AB - Motile cilia of the lungs respond to environmental challenges by increasing their ciliary beat frequency in order to enhance mucociliary clearance as a fundamental tenant of innate defense. One important second messenger in transducing the regulable nature of motile cilia is cyclic guanosine 3',5'-monophosphate (cGMP). In this review, the history of cGMP action is presented and a survey of the existing data addressing cGMP action in ciliary motility is presented. Nitric oxide (NO)-mediated regulation of cGMP in ciliated cells is presented in the context of alcohol-induced cilia function and dysfunction. PMID- 26264030 TI - Assessing the Surrogate Susceptibility of Oxacillin and Cefoxitin for Commonly Utilized Parenteral Agents against Methicillin-Susceptible Staphylococcus aureus: Focus on Ceftriaxone Discordance between Predictive Susceptibility and in Vivo Exposures. AB - Susceptibility testing with the use of surrogate agents is common among clinical microbiology laboratories. One such example is oxacillin and cefoxitin for beta lactams against methicillin-susceptible Staphylococcus aureus (MSSA). This study aimed to assess the surrogate predictive value (SPV) of oxacillin and cefoxitin for the susceptibility of commonly utilized parenteral beta-lactams against MSSA as well as to evaluate the concordance between predictive susceptibility testing and the in vivo exposures for ceftriaxone. Broth microdilution MICs were determined for cefazolin, cefoxitin, ceftaroline, ceftriaxone, nafcillin, and oxacillin against a national collection of 1238 MSSA from US hospitals. Pharmacodynamic profiling was utilized to establish a clinical breakpoint for commonly utilized doses of ceftriaxone. Oxacillin had good SPVs for all the beta lactams tested, whereas cefoxitin produced unacceptable major errors for all four agents and thus appears to be an unacceptable susceptibility surrogate. While oxacillin is an adequate surrogate based on the currently defined laboratory criteria, our data also suggest that caution should be exercised when incorporating this testing approach in the clinical setting in view of the fact that the MIC distribution of MSSA coupled with the commonly utilized low doses of ceftriaxone may result in inadequate in vivo exposures against this pathogen. PMID- 26264029 TI - Non-Overlapping Distributions and Functions of the VDAC Family in Ciliogenesis. AB - Centrosomes are major microtubule-organizing centers of animal cells that consist of two centrioles. In mitotic cells, centrosomes are duplicated to serve as the poles of the mitotic spindle, while in quiescent cells, centrosomes move to the apical membrane where the oldest centriole is transformed into a basal body to assemble a primary cilium. We recently showed that mitochondrial outer membrane porin VDAC3 localizes to centrosomes where it negatively regulates ciliogenesis. We show here that the other two family members, VDAC1 and VDAC2, best known for their function in mitochondrial bioenergetics, are also found at centrosomes. Like VDAC3, centrosomal VDAC1 is predominantly localized to the mother centriole, while VDAC2 localizes to centriolar satellites in a microtubule-dependent manner. Down-regulation of VDAC1 leads to inappropriate ciliogenesis, while its overexpression suppresses cilia formation, suggesting that VDAC1 and VDAC3 both negatively regulate ciliogenesis. However, this negative effect on ciliogenesis is not shared by VDAC2, which instead appears to promote maturation of primary cilia. Moreover, because overexpression of VDAC3 cannot compensate for depletion of VDAC1, our data suggest that while the entire VDAC family localizes to centrosomes, they have non-redundant functions in cilogenesis. PMID- 26264031 TI - Neural Adaptation Effects in Conceptual Processing. AB - We investigated the conceptual processing of nouns referring to objects characterized by a highly typical color and orientation. We used a go/no-go task in which we asked participants to categorize each noun as referring or not to natural entities (e.g., animals) after a selective adaptation of color-edge neurons in the posterior LV4 region of the visual cortex was induced by means of a McCollough effect procedure. This manipulation affected categorization: the green-vertical adaptation led to slower responses than the green-horizontal adaptation, regardless of the specific color and orientation of the to-be categorized noun. This result suggests that the conceptual processing of natural entities may entail the activation of modality-specific neural channels with weights proportional to the reliability of the signals produced by these channels during actual perception. This finding is discussed with reference to the debate about the grounded cognition view. PMID- 26264032 TI - Identification and Characterization of GABAergic Projection Neurons from Ventral Hippocampus to Amygdala. AB - GABAergic local circuit neurons are critical for the network activity and functional interaction of the amygdala and hippocampus. Previously, we obtained evidence for a GABAergic contribution to the hippocampal projection into the basolateral amygdala. Using fluorogold retrograde labeling, we now demonstrate that this projection indeed has a prominent GABAergic component comprising 17% of the GABAergic neurons in the ventral hippocampus. A majority of the identified GABAergic projection neurons are located in the stratum oriens of area CA1, but cells are also found in the stratum pyramidale and stratum radiatum. We could detect the expression of different markers of interneuron subpopulations, including parvalbumin and calbindin, somatostatin, neuropeptide Y, and cholecystokinin in such retrogradely labeled GABA neurons. Thus GABAergic projection neurons to the amygdala comprise a neurochemically heterogeneous group of cells from different interneuron populations, well situated to control network activity patterns in the amygdalo-hippocampal system. PMID- 26264033 TI - Aquaporin-Based Biomimetic Polymeric Membranes: Approaches and Challenges. AB - In recent years, aquaporin biomimetic membranes (ABMs) for water separation have gained considerable interest. Although the first ABMs are commercially available, there are still many challenges associated with further ABM development. Here, we discuss the interplay of the main components of ABMs: aquaporin proteins (AQPs), block copolymers for AQP reconstitution, and polymer-based supporting structures. First, we briefly cover challenges and review recent developments in understanding the interplay between AQP and block copolymers. Second, we review some experimental characterization methods for investigating AQP incorporation including freeze-fracture transmission electron microscopy, fluorescence correlation spectroscopy, stopped-flow light scattering, and small-angle X-ray scattering. Third, we focus on recent efforts in embedding reconstituted AQPs in membrane designs that are based on conventional thin film interfacial polymerization techniques. Finally, we describe some new developments in interfacial polymerization using polyhedral oligomeric silsesquioxane cages for increasing the physical and chemical durability of thin film composite membranes. PMID- 26264034 TI - Bioengineered Lacrimal Gland Organ Regeneration in Vivo. AB - The lacrimal gland plays an important role in maintaining a homeostatic environment for healthy ocular surfaces via tear secretion. Dry eye disease, which is caused by lacrimal gland dysfunction, is one of the most prevalent eye disorders and causes ocular discomfort, significant visual disturbances, and a reduced quality of life. Current therapies for dry eye disease, including artificial tear eye drops, are transient and palliative. The lacrimal gland, which consists of acini, ducts, and myoepithelial cells, develops from its organ germ via reciprocal epithelial-mesenchymal interactions during embryogenesis. Lacrimal tissue stem cells have been identified for use in regenerative therapeutic approaches aimed at restoring lacrimal gland functions. Fully functional organ replacement, such as for tooth and hair follicles, has also been developed via a novel three-dimensional stem cell manipulation, designated the Organ Germ Method, as a next-generation regenerative medicine. Recently, we successfully developed fully functional bioengineered lacrimal gland replacements after transplanting a bioengineered organ germ using this method. This study represented a significant advance in potential lacrimal gland organ replacement as a novel regenerative therapy for dry eye disease. In this review, we will summarize recent progress in lacrimal regeneration research and the development of bioengineered lacrimal gland organ replacement therapy. PMID- 26264035 TI - Intraocular Implants for the Treatment of Autoimmune Uveitis. AB - Uveitis is the third leading cause of blindness in developed countries. Currently, the most widely used treatment of non-infectious uveitis is corticosteroids. Posterior uveitis and macular edema can be treated with intraocular injection of corticosteroids, however, this is problematic in chronic cases because of the need for repeat injections. Another option is systemic immunosuppressive therapies that have their own undesirable side effects. These systemic therapies result in a widespread suppression of the entire immune system, leaving the patient susceptible to infection. Therefore, an effective localized treatment option is preferred. With the recent advances in bioengineering, biodegradable polymers that allow for a slow sustained-release of a medication. These advances have culminated in drug delivery implants that are food and drug administration (FDA) approved for the treatment of non-infectious uveitis. In this review, we discuss the types of ocular implants available and some of the polymers used, implants used for the treatment of non-infectious uveitis, and bioengineered alternatives that are on the horizon. PMID- 26264036 TI - Antibody Affinity Maturation in Fishes-Our Current Understanding. AB - It has long been believed that fish lack antibody affinity maturation, in part because they were thought to lack germinal centers. Recent research done on sharks and bony fishes indicates that these early vertebrates are able to affinity mature their antibodies. This article reviews the functionality of the fish homologue of the immunoglobulin (Ig) mutator enzyme activation-induced cytidine deaminase (AID). We also consider the protein and molecular evidence for Ig somatic hypermutation and antibody affinity maturation. In the context of recent evidence for a putative proto-germinal center in fishes we propose some possible reasons that observed affinity maturation in fishes often seems lacking and propose future work that might shed further light on this process in fishes. PMID- 26264037 TI - Removal of tetracycline from contaminated water by Moringa oleifera seed preparations. AB - The aim of this study was to evaluate tetracycline antibiotic (TA) removal from contaminated water by Moringa oleifera seed preparations. The composition of synthetic water approximate river natural contaminated water and TA simulated its presence as an emerging pollutant. Interactions between TA and protein preparations (extract; fraction and lectin) were also evaluated. TA was determined by solid-phase extraction followed by high-performance liquid chromatography-mass spectrometry. Moringa extract and flour removed TA from water. The extract removed TA in all concentrations, and better removal (40%) was obtained with 40 mg L(-1); seed flour (particles < 5 mm), 1.25 and 2.50 g L(-1) removed 28% and 29% of tetracycline, respectively; particles > 5 mm (0.50 g L( 1)) removed 55% of antibiotic. Interactions between TA and seed preparations were assayed by haemagglutinating activity (HA). Specific HA (SHA) of extract (pH 7) was abolished with tetracycline (5 mg L(-1)); fraction (75%) and lectin HA (97%) were inhibited with TA. Extract SHA decreased by 75% at pH 8. Zeta potential (ZP) of extract 700 mg L(-1) and tetracycline 50 mg L(-1) , pH range 5-8, showed different results. Extract ZP was more negative (-10.73 to -16.00 mV) than tetracycline ZP (-0.27 to -20.15 mV); ZP difference was greater in pH 8. The focus of this study was achieved since Moringa preparations removed TA from water and compounds interacting with tetracycline involved at least lectin-binding sites. This is a natural process, which do not promote environmental damage. PMID- 26264038 TI - Is there a relationship between genetic merit and enteric methane emission rate of lactating Holstein-Friesian dairy cows? AB - The present study was undertaken to examine the effect of cow genetic merit on enteric methane (CH4) emission rate. The study used a data set from 32 respiration calorimeter studies undertaken at this Institute between 1992 and 2010, with all studies involving lactating Holstein-Friesian dairy cows. Cow genetic merit was defined as either profit index (PIN) or profitable lifetime index (PLI), with these two United Kingdom genetic indexes expressing the expected improvement in profit associated with an individual cow, compared with the population average. While PIN is based solely on milk production, PLI includes milk production and a number of other functional traits including health, fertility and longevity. The data set had a large range in PIN (n=736 records, -L30 to +L63) and PLI (n=548 records, -L131 to +L184), days in milk (18 to 354), energy corrected milk yield (16.0 to 45.6 kg/day) and CH(4) emission (138 to 598 g/day). The effect of cow genetic merit (PIN or PLI) was evaluated using ANOVA and linear mixed modelling techniques after removing the effects of a number of animal and diet factors. The ANOVA was undertaken by dividing each data set of PIN and PLI into three sub-groups (PIN:L15, PLI:L67) with these being categorised as low, medium and high genetic merit. Within the PIN and PLI data sets there was no significant differences among the three sub-groups in terms of CH(4) emission per kg feed intake or per kg energy corrected milk yield, or CH(4) energy (CH(4)-E) output as a proportion of energy intake. Linear regression using the whole PIN and PLI data sets also demonstrated that there was no significant relationship between either PIN or PLI, and CH(4) emission per kg of feed intake or CH(4)-E output as a proportion of energy intake. These results indicate that cow genetic merit (PIN or PLI) has little effect on enteric CH(4) emissions as a proportion of feed intake. Instead enteric CH(4) production may mainly relate to total feed intake and dietary nutrient composition. PMID- 26264039 TI - Neuroprotective effect of Tagara, an Ayurvedic drug against methyl mercury induced oxidative stress using rat brain mitochondrial fractions. AB - BACKGROUND: Methyl mercury (MeHg), an important environmental toxicant is implicated in neurological disorders such as Hunter-Russell syndrome and Autism. Therefore, the present work is in search of new drugs that can alleviate MeHg toxicity. In this connection, Tagara, an ayurvedic drug is used for assessing its neuro protective effect against MeHg toxicity. METHODS: In the present study, we assessed the phytochemical contents of Tagara by colorimetric and HPLC analyses. The neuroprotective effect of Tagara on MeHg induced neurotoxicity was measured in terms of viability by MTT assay and oxidative stress in terms of catalase activity, glutathione and thiobarbituric acid reactive substance levels. Further, the chelating effect of Tagara towards MeHg was performed to identify the molecular mechanism. Statistical analysis was done by statistical package for social sciences (SPSS) version 16.0. RESULTS: The results demonstrated that Tagara contains significant amounts of phenols and flavonoids. Also, HPLC analysis of Tagara revealed the presence of essential oils such as hydroxyvalerenic and valerenic acids. Our results demonstrated that exposure of rat brain mitochondrial fractions to MeHg resulted in a dose dependent death in MTT assay and IC50 value was found to be 10 MUM. However, a 250 MUg dose of Tagara effectively prevented MeHg induced mitochondrial damage. The oxidative stress caused by MeHg results in elevated levels of reactive oxygen species as evidenced by elevated TBARS (Thiobarbituric acid-reactive substances) levels and diminished catalase enzyme activity and glutathione content. However, Tagara at 250 MUg concentration offsets these alterations caused by MeHg. Further, Tagara also diminished GSH oxidation caused by MeHg, confirming its chelating effect, one of the molecular mechanisms that triggers protection against oxidative damage. CONCLUSION: Our results revealed that MeHg induced toxicity is predominantly mediated through oxidative stress mechanism and the propensity of Tagara to abolish such reactions. Hence, we propose that Tagara with a source of potential neuroprotectants may be a useful approach to alleviate MeHg associated neurotoxicity. PMID- 26264040 TI - Alcohol intake and associated risk of major cardiovascular outcomes in women compared with men: a systematic review and meta-analysis of prospective observational studies. AB - BACKGROUND: The prevalence of alcohol intake is increasing among women in some populations. Alcohol consumption plays an important role in the risk of major cardiovascular outcomes and total mortality. Here, we conducted a meta-analysis to estimate the association between alcohol intake and major cardiovascular outcomes or total mortality in women compared with men. METHODS: We searched the PubMed, Embase, and the Cochrane Library databases for relevant articles published prior to June 2014. Among these potential included prospective studies, the different dose categories of alcohol intake were compared with the lowest alcohol intake or non-drinkers between women and men for the outcomes of major cardiovascular or total mortality. RESULTS: We included 23 prospective studies (18 cohorts) reporting data on 489,696 individuals. The summary relative risk ratio (RRR; female to male) for total mortality was significantly increased with moderate alcohol intake compared with the lowest alcohol intake (RRR, 1.10; 95 % confidence interval [CI]: 1.00-1.21; P = 0.047); no such significance was observed with other levels of alcohol intake (low intake: RRR, 1.07; 95 % CI: 0.98-1.17; P = 0.143; heavy intake: RRR, 1.09; 95 % CI: 0.99-1.21; P = 0.084). There was no evidence of a sex difference in the relative risk for coronary disease, cardiac death, stroke, or ischemic stroke between participants with low to heavy alcohol intake compared with those who never consumed alcohol or had the lowest alcohol intake. CONCLUSIONS: Women with moderate to heavy alcohol intake had a significantly increased risk of total mortality compared with men in multiple subpopulations. Control of alcohol intake should be considered for women, particularly for young women who may be susceptible to binge drinking. PMID- 26264041 TI - Association of SNPs in LCP1 and CTIF with hearing in 11 year old children: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort and the G-EAR consortium. AB - BACKGROUND: The genetic basis of hearing loss in humans is relatively poorly understood. In recent years, experimental approaches including laboratory studies of early onset hearing loss in inbred mouse strains, or proteomic analyses of hair cells or hair bundles, have suggested new candidate molecules involved in hearing function. However, the relevance of these genes/gene products to hearing function in humans remains unknown. We investigated whether single nucleotide polymorphisms (SNPs) in the human orthologues of genes of interest arising from the above-mentioned studies correlate with hearing function in children. METHODS: 577 SNPs from 13 genes were each analysed by linear regression against averaged high (3, 4 and 8 kHz) or low frequency (0.5, 1 and 2 kHz) audiometry data from 4970 children in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth-cohort at age eleven years. Genes found to contain SNPs with low p-values were then investigated in 3417 adults in the G-EAR study of hearing. RESULTS: Genotypic data were available in ALSPAC for a total of 577 SNPs from 13 genes of interest. Two SNPs approached sample-wide significance (pre-specified at p = 0.00014): rs12959910 in CBP80/20-dependent translation initiation factor (CTIF) for averaged high frequency hearing (p = 0.00079, beta = 0.61 dB per minor allele); and rs10492452 in L-plastin (LCP1) for averaged low frequency hearing (p = 0.00056, beta = 0.45 dB). For low frequencies, rs9567638 in LCP1 also enhanced hearing in females (p = 0.0011, beta = -1.76 dB; males p = 0.23, beta = 0.61 dB, likelihood-ratio test p = 0.006). SNPs in LCP1 and CTIF were then examined against low and high frequency hearing data for adults in G-EAR. Although the ALSPAC results were not replicated, a SNP in LCP1, rs17601960, is in strong LD with rs9967638, and was associated with enhanced low frequency hearing in adult females in G-EAR (p = 0.00084). CONCLUSIONS: There was evidence to suggest that multiple SNPs in CTIF may contribute a small detrimental effect to hearing, and that a sex-specific locus in LCP1 is protective of hearing. No individual SNPs reached sample-wide significance in both ALSPAC and G-EAR. This is the first report of a possible association between LCP1 and hearing function. PMID- 26264042 TI - Cilantro microbiome before and after nonselective pre-enrichment for Salmonella using 16S rRNA and metagenomic sequencing. AB - BACKGROUND: Salmonella enterica is a common cause of foodborne gastroenteritis in the United States and is associated with outbreaks in fresh produce such as cilantro. Salmonella culture-based detection methods are complex and time consuming, and improvments to increase detection sensitivity will benefit consumers. In this study, we used 16S rRNA sequencing to determine the microbiome of cilantro. We also investigated changes to the microbial community prior to and after a 24-hour nonselective pre-enrichment culture step commonly used by laboratory analysts to resuscitate microorganisms in foods suspected of contamination with pathogens. Cilantro samples were processed for Salmonella detection according to the method in the United States Food and Drug Administration Bacteriological Analytical Manual. Genomic DNA was extracted from culture supernatants prior to and after a 24-hour nonselective pre-enrichment step and 454 pyrosequencing was performed on 16S rRNA amplicon libraries. A database of Enterobacteriaceae 16S rRNA sequences was created, and used to screen the libraries for Salmonella, as some samples were known to be culture positive. Additionally, culture positive cilantro samples were examined for the presence of Salmonella using shotgun metagenomics on the Illumina MiSeq. RESULTS: Time zero uncultured samples had an abundance of Proteobacteria while the 24-hour enriched samples were composed mostly of Gram-positive Firmicutes. Shotgun metagenomic sequencing of Salmonella culture positive cilantro samples revealed variable degrees of Salmonella contamination among the sequenced samples. CONCLUSIONS: Our cilantro study demonstrates the use of high-throughput sequencing to reveal the microbiome of cilantro, and how the microbiome changes during the culture-based protocols employed by food safety laboratories to detect foodborne pathogens. Finding that culturing the cilantro shifts the microbiome to a predominance of Firmicutes suggests that changing our culture-based methods will improve detection sensitivity for foodborne enteric pathogens. PMID- 26264043 TI - Responsiveness, construct and criterion validity of the Personal Care Participation Assessment and Resource Tool (PC-PART). AB - BACKGROUND: The Personal Care-Participation Assessment and Resource Tool (PC PART) was designed to measure participation restrictions in activities of daily living required for community life. Rasch analysis has confirmed that the PC-PART contains two unidimensional scales providing interval-level measurement: the Self Care and Domestic Life scales. This study investigated validity and responsiveness of these PC-PART scales using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) approach. METHODS: Thirteen hypotheses about Self Care and Domestic Life scale scores were established prior to conducting the analyses. Data from a prospective randomized controlled trial of additional (weekend) inpatient rehabilitation in Melbourne, Australia, were used. The 996 participants had a mean (SD) age of 74 (13) years and were admitted with orthopaedic (n = 581), neurological (n = 203) or other disabling impairments (n = 212). Self Care and Domestic Life scores were compared to functional independence (FIM), comorbidity (Charlson Comorbidity Index), whether activities of daily living goals were met, and discharge destination. RESULTS: Low to moderate correlations between FIM and PC-PART scales' scores supported hypotheses that the PC-PART measures a different construct from functional independence: Self Care r s -0.52(95 % CI -.46 to -.57) and Domestic Life r s -0.32(95 % CI -.25 to -.38). The scales had low to moderate discriminative ability for discharge destination, with the area under the curve for Self Care, 0.70 (95 % CI 0.62-0.78), and Domestic Life, 0.72 (95 % CI 0.64 0.80). The discharge to community living cut-off scores for Self Care: 5.50 (sensitivity .83, specificity .53) and Domestic Life: 7.50 (sensitivity .75, specificity .60), represented patients having no participation restrictions. Change scores from admission to discharge demonstrated larger effect sizes for the Self Care (1.67) and Domestic Life (1.50) scales than for the FIM (1.10), supporting hypotheses about responsiveness. Ten of the 13 hypotheses were supported. CONCLUSIONS: This study provided evidence supporting construct validity, criterion validity and responsiveness of the PC-PART Self Care and Domestic Life scales for inpatient rehabilitation. Clinicians, managers and researchers who wish to measure the patterns and extent of people's participation restrictions in activities of daily living and the associated burden of care, before and/or after intervention, can be somewhat confident about the PC-PART's validity and responsiveness for this purpose. TRIAL REGISTRATION: Data used in this research were gathered during a registered randomized controlled trial: Australian and New Zealand Clinical Trials Registry ACTRN12609000973213. PMID- 26264044 TI - Ossifying metaplasia of urothelial metastases: original case with review of the literature. AB - BACKGROUND: Ossifying metaplasia is an unusual feature of urothelial carcinoma, with only a few cases reported. The largest series included 17 cases and was published in 1991. The mechanism of ossification is unknown and hypotheses of osteogenic precursor cells, inducing bone formation, are proposed. CASE PRESENTATION: A 75 year-old patient was treated for a high grade transitional cell carcinoma of the bladder by surgery, chemotherapy and radiotherapy. Histology showed foci of bone metaplasia, both at the periphery of the tumor, and in a lymph node metastasis. 1 year later, a heterotopic bone formation was discovered in the right retroperitoneal space, near the lumbar spine, increasing rapidly in size during follow-up. Several imaging exams were performed (2 CT, 1 MRI, 1 Pet-CT), but in the absence of typical features of sarcoma, diagnosis remained unclear. Histology of a CT-guided percutaneous biopsy showed urothelial carcinoma and mature lamellar bone. Integration of these findings with the radiological description of extraosseous localization was consistent with a diagnosis of osseous metaplasia of an urothelial carcinoma metastasis. The absence of bone atypia in both the primary and metastases argues against sarcomatoid urothelial carcinoma with osteosarcomatous differentiation. CONCLUSION: Osseous metaplasia of an urothelial carcinoma metastasis is unusual, and difficult to distinguish from radiotherapy induced sarcoma, or from sarcomatoid carcinoma. Rapid progression, sheathing of adjacent structures such as vessels (like inferior vena cava in our case) and nerves and bony feature of lymph node metastases necessitate histological confirmation and rapid treatment. Our case illustrates this disease and evaluates the imaging features. In addition we discuss the differential diagnosis of osseous retroperitoneal masses. PMID- 26264045 TI - Effects of Methylmercury on Harbour Seal Peripheral Blood Leucocytes In Vitro Studied by Electron Microscopy. AB - Methylmercury (MeHg) is highly immunotoxic and can alter the health status of the harbour seal, Phoca vitulina, from the North Sea. To investigate the mechanism of MeHg-induced toxicity in harbour seal lymphocytes, Concanavalin A (ConA) stimulated peripheral blood leucocytes were exposed in vitro to sublethal concentrations of MeHgCl (0.2, 1, and 2 uM) for 72 h and then analysed for their viability and ultrastructure. After 72 h of incubation, cells were counted with a propidium iodide staining technique, a metabolic MTS assay was performed, and cells exposed to 1 uM of MeHgCl were observed by transmission electron microscopy (TEM). Alive cell numbers decreased with increased MeHgCl concentrations. In presence of ConA and 1 uM of MeHgCl, TEM images revealed a higher frequency of apoptotic cells. Exposed cells displayed condensation of the chromatin at the nuclear membrane and mitochondrial damages. The results suggest that in vitro MeHgCl-induced apoptosis in harbour seal lymphocytes through a mitochondrial pathway. PMID- 26264046 TI - Potential Threat of Microplastics to Zooplanktivores in the Surface Waters of the Southern Sea of Korea. AB - The potential impact of microplastic to zooplanktivores was assessed by measuring a ratio of neustonic microplastics to zooplankton by abundance in the southern sea of Korea. Neustonic microplastics and zooplankton (0.33-2 mm) were collected using a 330-MUm mesh Manta trawl in Geoje eastern Bay and Jinhae Bay before and after the rainy season in 2012 and 2013. The mean microplastic to zooplankton ratios were 0.086 (May) and 0.022 (July) in 2012, and 0.016 (June) and 0.004 (July) in 2013, indicating that zooplanktivores could be more likely to feed on microplastics than natural preys before the rainy season in 2012 and 2013. In particular, the relatively high ratio occurred in a semi-enclosed bay characterized by a shipyard and a beach resort in Geoje Bay, and at stations close to a wastewater treatment plant and an aquaculture facility in Jinhae Bay before the rainy season. Among dominant microplastics and zooplankton before the rainy season, meroplankton of macrobenthos could be confused with paint particles in Geoje Bay, 2012, whereas Styrofoam could be mistaken as immature copepods by predators in Jinhae Bay, 2013. These observations suggest that zooplanktivores could be more likely to feed on microplastics than natural preys around Geoje and Jinhae Bays before the rainy season. PMID- 26264047 TI - Quantification of autofluorescence imaging can accurately and objectively assess the severity of ulcerative colitis. AB - BACKGROUND AND AIMS: No endoscopic examination has been able to evaluate severity of ulcerative colitis (UC) by quantification. This prospective study investigated the efficacy of quantifying autofluorescence imaging (AFI) to assess the severity of UC, which captures the fluorescence emitted from intestinal tissue and then quantifies the intensity using an image-analytical software program. MATERIALS AND METHODS: Eleven endoscopists separately evaluated 135 images of conventional endoscopy (CE) and AFI from a same lesion. A CE image corresponding to Mayo endoscopic subscore 0 or 1 was defined as being inactive. The fluorescence intensities of AFI were quantified using an image-analytical software program (F index; FI). Active inflammation was defined when Matts' histological grade was 2 or more. A cut-off value of the FI for active inflammation was determined using a receiver operating characteristic (ROC) analysis. The inter-observer consistency was calculated by unweighted kappa statistics. RESULTS: The correlation coefficient for the FI was inversely related to the histological severity (r = 0.558, p < 0.0001). The ROC analysis showed that the optimal cut-off value for the FI for active inflammation was 0.906. The average diagnostic accuracy of the FI was significantly higher than those of the CE (84.7 vs 78.5 %, p < 0.01). The kappa values for the inter-observer consistency of CE and the FI were 0.60 and 0.95 in all participants, 0.53 and 0.97 in the less-experienced endoscopists group and 0.67 and 0.93 in the expert group, respectively. CONCLUSIONS: The quantified AFI is considered to be an accurate and objective indicator that can be used to assess the activity of ulcerative colitis, particularly for less experienced endoscopists. PMID- 26264048 TI - Urinary and sexual dysfunction rates and risk factors following rectal cancer surgery. AB - OBJECTIVE: The aim of this study was to express the effects of demographic characteristics, the type of the surgery, tumour characteristics and adjuvant therapy on urinary and sexual dysfunctions. MATERIALS AND METHOD: Pre-operational urinary and sexual dysfunctions of the patients were evaluated by using the surveys prepared according to International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF) in men and Index of Female Sexual Function (IFSF) in women. FINDINGS: A total of 56 patients were included in the study; 20 of them were women and 36 of them were men. The mean age was 56. Abdominoperineal resection (APR) was performed on 11 patients, and low anterior resection (LAR) was performed on 45. The post-treatment IPSS classes were worsened at a rate of 12.7 % compared to the pre-treatment. The mean post treatment sexual dysfunction score of both men and women were decreased by 27.5 and 17.8 %, respectively. Rectal tumours located in the lower part resulted in more sexual dysfunction. CONCLUSION: The tumour in the 1/3 lower part of the rectal area was determined to be the most effective factor that caused both urinary and sexual dysfunction. Patients should be informed about the urinary and sexual dysfunctions in the pre-operative consultations. PMID- 26264049 TI - Risk of readmission after laparoscopic vs. open colorectal surgery. AB - PURPOSE: Laparoscopic colorectal resection (LC) is associated with known recovery benefits and earlier discharge when compared to open colorectal resection (OC). Whether earlier discharge leads to a paradoxical increase in readmission has not been well characterized. The aim of this study is to compare the risk of readmission after the two procedures in a large, nationally representative sample. METHODS: Patients who underwent colorectal resection in 2011 were identified from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database. LC and OC patients were compared for patient factors, complications, and readmission rates. A multivariable analysis controlling for significant factors was performed to evaluate factors associated with readmission. RESULTS: Of 30,428 patients who underwent colorectal resection, 40.2% underwent LC. Length of stay (LOS) after LC was shorter than after OC (5.7 vs. 9.7 days, p < 0.001). LC was associated with a significantly lower rate of surgical site infections (SSI), bleeding, reoperation, 30-day mortality, and complications. Risk of readmission was greater for patients undergoing proctectomy than colectomy (12.7 vs. 10.6 %, p < 0.001), but was lower after laparoscopic than open for both procedures after controlling for confounding factors. Obesity, DM, operating time >=180 min, steroid use, and ASA class 3-5 were found to be associated with readmission. CONCLUSION: Despite its technical complexity, LC can be performed without concerns for increased complications or readmission. The shorter length of stay and the lower risk of readmissions underline the true benefits of the laparoscopic approach for colorectal resection. PMID- 26264050 TI - Modifications of perineuronal nets and remodelling of excitatory and inhibitory afferents during vestibular compensation in the adult mouse. AB - Perineuronal nets (PNNs) are aggregates of extracellular matrix molecules surrounding several types of neurons in the adult CNS, which contribute to stabilising neuronal connections. Interestingly, a reduction of PNN number and staining intensity has been observed in conditions associated with plasticity in the adult brain. However, it is not known whether spontaneous PNN changes are functional to plasticity and repair after injury. To address this issue, we investigated PNN expression in the vestibular nuclei of the adult mouse during vestibular compensation, namely the resolution of motor deficits resulting from a unilateral peripheral vestibular lesion. After unilateral labyrinthectomy, we found that PNN number and staining intensity were strongly attenuated in the lateral vestibular nucleus on both sides, in parallel with remodelling of excitatory and inhibitory afferents. Moreover, PNNs were completely restored when vestibular deficits of the mice were abated. Interestingly, in mice with genetically reduced PNNs, vestibular compensation was accelerated. Overall, these results strongly suggest that temporal tuning of PNN expression may be crucial for vestibular compensation. PMID- 26264051 TI - Erratum to: Birth defects and congenital health risks in children conceived through assisted reproduction technology (ART): a meeting report. PMID- 26264052 TI - Subdivision of M category for nasopharyngeal carcinoma with synchronous metastasis: time to expand the M categorization system. AB - INTRODUCTION: The current metastatic category (M) of nasopharyngeal carcinoma (NPC) is a "catch-all" classification, covering a heterogeneous group of tumors ranging from potentially curable to incurable. The aim of this study was to design an M categorization system that could be applied in planning the treatment of NPC with synchronous metastasis. METHODS: A total of 505 NPC patients diagnosed with synchronous metastasis at Sun Yat-sen University Cancer Center between 2000 and 2009 were involved. The associations of clinical variables, metastatic features, and a proposed M categorization system with overall survival (OS) were determined by using Cox regression model. RESULTS: Multivariate analysis showed that Union for International Cancer Control (UICC) N category (N1 3/N0), number of metastatic lesions (multiple/single), liver involvement (yes/no), radiotherapy to primary tumor (yes/no), and cycles of chemotherapy (>4/<=4) were independent prognostic factors for OS. We defined the following subcategories based on liver involvement and the number of metastatic lesions: M1a, single lesion confined to an isolated organ or location except the liver; M1b, single lesion in the liver and/or multiple lesions in any organs or locations except the liver; and M1c, multiple lesions in the liver. Of the 505 cases, 74 (14.7%) were classified as M1a, 296 (58.6%) as M1b, 134 (26.5%) as M1c, and 1 was not specified. The three M1 subcategories showed significant difference in OS [M1b vs. M1a, hazard ratio (HR) = 1.69, 95% confidence interval (CI) = 1.16 2.48, P = 0.007; M1c vs. M1a, HR = 2.64, 95% CI = 1.75-3.98, P < 0.001]. CONCLUSIONS: We developed an M categorization system based on the independent factors related to the prognosis of patients with metastatic NPC. This system may be helpful to further optimize individualized care for NPC patients. PMID- 26264053 TI - StressMicrobesInfo: Database of Microorganisms Responsive to Stress Conditions. AB - Microorganisms are continuously exposed to numerous stress conditions and had evolved with numerous evolutionary adaptations and physiological acclimation mechanisms against stress effects. Any information related to the microbes responsive to stress conditions will help scientists working in the area of stress biology. Currently, there is lack of information resource on this aspect and for getting information about microbes susceptible or tolerant to different environmental changes, literature searching is the only option. Here, we present a database StressMicrobesInfo that was developed with a mandate to provide information about microbes responding to various biotic and abiotic stress conditions. This database currently contains information about 183 microbes along with a brief detail for each. StressMicrobesInfo will facilitate researchers working on stress-related microbes as a starting point and will facilitate them with the microbes which are susceptible or resistant towards particular stress conditions. PMID- 26264054 TI - In Silico Elucidation and Inhibition Studies of Selected Phytoligands Against Mitogen-Activated Protein Kinases of Protozoan Parasites. AB - Parasitic MAPKs exhibiting significant divergence with humans and playing an imperative role in parasitic metabolic activities have been exploited from several years as important targets for development of novel therapeutics. In addition, the emergence of the drug-resistant variants of parasitic diseases in the recent years has aroused a great need for the development of potent inhibitors against them. In the present study, we selected the metabolically active MAPKs LmxMPK4, PfMAP2 and TbMAPK5 of the three parasitic protozoans Leishmania mexicana, Plasmodium falciparum and Trypanosoma brucei, respectively. The homology modeling technique was used to develop the 3D structures of these proteins, and the same was validated by PROCHECK, ERRAT, ProQ and ProSA web servers to check the reliability. Ten phytoligands were employed for molecular docking studies with these proteins to search for potent phytoligand as a broad spectrum inhibitor. In this regard, two phytoligands (aspidocarpine for LmxMPK4 and TbMAPK5 and cubebin for PfMAP2) were found to be more effective inhibitors, in terms of robust binding energy, strong inhibition constant and better interactions between protein-ligand complexes. Furthermore, predicted ADME and toxicity properties suggested that these identified phytoligands exhibited comparable results to control drugs potentiating them as persuasive therapeutic agents for Leishmania, Trypanosoma and Plasmodium sp. PMID- 26264055 TI - Evolving-Pattern Analysis of Transient and Long-Term Biomarkers for Cancers: Hepatocellular Carcinoma as a Case. AB - Cancer is a complex disease arises from combinations of changes that occur over a period of time. With the development of bioinformatics, more and more biomarkers representing changes in cancers had been identified using gene expression profiles. However, biomarkers alone are quite limited in explaining the molecular processes occurred in the due process. In this paper, we develop an evolving pattern analysis pipeline for in-depth studies of gene expression changes during different disease stages, choosing hepatocellular carcinoma (HCC) as a case. Enrichment analyses were performed on three levels: functional terms, validated genes, and regulation factors for all the biomarkers to find out their biological characters. Our results show that biomarkers with distinct evolving patterns exhibit quite different characteristics on functional and regulation levels. For the case of HCC, transient biomarkers are mostly annotated to metabolic processes, while long-term biomarkers are mostly annotated to regulation processes, with a larger number of enriched regulation factors. Furthermore, our pipeline reveals the important roles of microRNAs in various evolving patterns, which are known to be closely related to HCC. These results confirm that evolving pattern analysis may provide a new sight for in-depth studies of biomarkers and diseases. PMID- 26264056 TI - Comparative Analysis of the Molecular Adjuvants and Their Binding Efficiency with CR1. AB - There are so many obstacles in developing a vaccine or vaccine technology for diseases like cancer and human immunodeficiency virus infection. While developing vaccines that target specific infection, molecular adjuvants are indispensable. These molecular adjuvants act as a vaccine delivery vehicle to the immune system to increase the effectiveness of the specific antigens. In the present work, a computational study has been done on molecular adjuvants like IgGFc, GMCSF and C3d to find out how efficiently they are binding to CR1. Sequence, structure and mutational analysis are performed on the molecular adjuvants to understand the features important for their binding with the receptor. Results obtained from our study indicate that the adjuvant IgGFc complexed with the receptor CR1 has the best binding efficiency, which can be used further to develop better vaccine technologies. PMID- 26264057 TI - Heart rate analysis by sparse representation for acute pain detection. AB - Objective pain assessment methods pose an advantage over the currently used subjective pain rating tools. Advanced signal processing methodologies, including the wavelet transform (WT) and the orthogonal matching pursuit algorithm (OMP), were developed in the past two decades. The aim of this study was to apply and compare these time-specific methods to heart rate samples of healthy subjects for acute pain detection. Fifteen adult volunteers participated in a study conducted in the pain clinic at a single center. Each subject's heart rate was sampled for 5-min baseline, followed by a cold pressor test (CPT). Analysis was done by the WT and the OMP algorithm with a Fourier/Wavelet dictionary separately. Data from 11 subjects were analyzed. Compared to baseline, The WT analysis showed a significant coefficients' density increase during the pain incline period (p < 0.01) and the entire CPT (p < 0.01), with significantly higher coefficient amplitudes. The OMP analysis showed a significant wavelet coefficients' density increase during pain incline and decline periods (p < 0.01, p < 0.05) and the entire CPT (p < 0.001), with suggestive higher amplitudes. Comparison of both methods showed that during the baseline there was a significant reduction in wavelet coefficient density using the OMP algorithm (p < 0.001). Analysis by the two-way ANOVA with repeated measures showed a significant proportional increase in wavelet coefficients during the incline period and the entire CPT using the OMP algorithm (p < 0.01). Both methods provided accurate and non-delayed detection of pain events. Statistical analysis proved the OMP to be by far more specific allowing the Fourier coefficients to represent the signal's basic harmonics and the wavelet coefficients to focus on the time-specific painful event. This is an initial study using OMP for pain detection; further studies need to prove the efficiency of this system in different settings. PMID- 26264058 TI - Identifying relevant group of miRNAs in cancer using fuzzy mutual information. AB - MicroRNAs (miRNAs) act as a major biomarker of cancer. All miRNAs in human body are not equally important for cancer identification. We propose a methodology, called FMIMS, which automatically selects the most relevant miRNAs for a particular type of cancer. In FMIMS, miRNAs are initially grouped by using a SVM based algorithm; then the group with highest relevance is determined and the miRNAs in that group are finally ranked for selection according to their redundancy. Fuzzy mutual information is used in computing the relevance of a group and the redundancy of miRNAs within it. Superiority of the most relevant group to all others, in deciding normal or cancer, is demonstrated on breast, renal, colorectal, lung, melanoma and prostate data. The merit of FMIMS as compared to several existing methods is established. While 12 out of 15 selected miRNAs by FMIMS corroborate with those of biological investigations, three of them viz., "hsa-miR-519," "hsa-miR-431" and "hsa-miR-320c" are possible novel predictions for renal cancer, lung cancer and melanoma, respectively. The selected miRNAs are found to be involved in disease-specific pathways by targeting various genes. The method is also able to detect the responsible miRNAs even at the primary stage of cancer. The related code is available at http://www.jayanta.droppages.com/FMIMS.html . PMID- 26264059 TI - A new device combining mechanical stimulation of plantar sole and Achilles' tendon to alleviate the consequences of muscle deconditioning. AB - Limb immobilization or confinement to bed results in a severe atrophy and weakness of lower leg muscles. Full recovery of muscle strength and physical function is rare and may impact the patient's outcome. Studies performed on rodents have demonstrated that the deleterious structural and functional adaptations which occur during muscle deconditioning can be counteracted through adequate physiological stimuli. Thus, based on this fundamental work, we developed a device that combines mechanical stimulation of proprioceptors located in the plantar sole and Achilles' tendon. The device is adapted to patients immobilized and confined to bed. Stimulations can be applied on muscle in passive state. The protocol is non-invasive and is well accepted by patients. This paper presents the technical features of the device, as well as preliminary results of the first clinical study. This device might allow considering new therapeutic strategies for prevention of atrophy in many pathologies. PMID- 26264060 TI - Abstracts of 51st EASD Annual Meeting. PMID- 26264062 TI - Analysis of the xynB5 gene encoding a multifunctional GH3-BglX beta-glucosidase beta-xylosidase-alpha-arabinosidase member in Caulobacter crescentus. AB - The Caulobacter crescentus (NA1000) xynB5 gene (CCNA_03149) encodes a predicted beta-glucosidase-beta-xylosidase enzyme that was amplified by polymerase chain reaction; the product was cloned into the blunt ends of the pJet1.2 plasmid. Analysis of the protein sequence indicated the presence of conserved glycosyl hydrolase 3 (GH3), beta-glucosidase-related glycosidase (BglX) and fibronectin type III-like domains. After verifying its identity by DNA sequencing, the xynB5 gene was linked to an amino-terminal His-tag using the pTrcHisA vector. A recombinant protein (95 kDa) was successfully overexpressed from the xynB5 gene in E. coli Top 10 and purified using pre-packed nickel-Sepharose columns. The purified protein (BglX-V-Ara) demonstrated multifunctional activities in the presence of different substrates for beta-glucosidase (pNPG: p-nitrophenyl-beta-D glucoside) beta-xylosidase (pNPX: p-nitrophenyl-beta-D-xyloside) and alpha arabinosidase (pNPA: p-nitrophenyl-alpha-L-arabinosidase). BglX-V-Ara presented an optimal pH of 6 for all substrates and optimal temperature of 50 degrees C for beta-glucosidase and alpha-L-arabinosidase and 60 degrees C for beta xylosidase. BglX-V-Ara predominantly presented beta-glucosidase activity, with the highest affinity for its substrate and catalytic efficiency (Km 0.24 +/- 0.0005 mM, Vmax 0.041 +/- 0.002 umol min(-1) mg(-1) and Kcat/Km 0.27 mM(-1) s( 1)), followed by beta-xylosidase (Km 0.64 +/- 0.032 mM, Vmax 0.055 +/- 0.002 umol min(-1) mg(-1) and Kcat/Km 0.14 mM(-1)s(-1)) and finally alpha-L-arabinosidase (Km 1.45 +/- 0.05 mM, Vmax 0.091 +/- 0.0004 umol min(-1) mg(-1) and Kcat/Km 0.1 mM(-1) s(-1)). To date, this is the first report to demonstrate the characterization of a GH3-BglX family member in C. crescentus that may have applications in biotechnological processes (i.e., the simultaneous saccharification process) because the multifunctional enzyme could play an important role in bacterial hemicellulose degradation. PMID- 26264061 TI - Physical activity attenuates the mid-adolescent peak in insulin resistance but by late adolescence the effect is lost: a longitudinal study with annual measures from 9-16 years (EarlyBird 66). AB - AIMS/HYPOTHESIS: The aim of this work was to test whether the mid-adolescent peak in insulin resistance (IR) and trends in other metabolic markers are influenced by long-term exposure to physical activity. METHODS: Physical activity (7 day ActiGraph accelerometry), HOMA-IR and other metabolic markers (glucose, fasting insulin, HbA1c, lipids and BP) were measured annually from age 9 years to 16 years in 300 children (151 boys) from the EarlyBird study in Plymouth, UK. The activity level of each child was characterised, with 95% reliability, by averaging their eight annual physical activity measures. Age-related trends in IR and metabolic health were analysed by multi-level modelling, with physical activity as the exposure measure (categorical and continuous) and body fat percentage (assessed by dual-energy X-ray absorptiometry) and pubertal status (according to age at peak height velocity and Tanner stage) as covariates. RESULTS: The peak in IR at age 12-13 years was 17% lower (p < 0.001) in the more active adolescents independently of body fat percentage and pubertal status. However, this difference diminished progressively over the next 3 years and had disappeared completely by the age of 16 years (e.g. difference was -14% at 14 years, -8% at 15 years and +1% at 16 years; 'physical activity * age(2), interaction, p < 0.01). Triacylglycerol levels in girls (-9.7%, p = 0.05) and diastolic blood pressure in boys (-1.20 mmHg, p = 0.03) tended to be lower throughout adolescence in the more active group. CONCLUSIONS/INTERPRETATION: Our finding that physical activity attenuates IR during mid-adolescence may be clinically important. It remains to be established whether the temporary attenuation in IR during this period has implications for the development of diabetes in adolescence and for future metabolic health generally. PMID- 26264063 TI - Pachymeningeal enhancement-a comprehensive review of literature. AB - Pachymeningeal enhancement, synonymous with dural enhancement, is a radiological feature best appreciated on a contrast-enhanced magnetic resonance imaging (MRI). The vasculature of the dura mater is permeable, facilitating avid uptake of contrast agent and subsequent enhancement. Thin, discontinuous enhancement can be normal, seen in half the normal population. In patients complaining of postural headaches worse on sitting, gadolinium-enhanced MRI findings of diffuse pachymeningeal enhancement is highly suggestive of benign intracranial hypotension. In these cases, the process of pachymeningeal enhancement is explained by the Monro-Kellie doctrine as compensatory volume changes by vasocongestion and interstitial oedema of the dura mater due to decreased cerebrospinal fluid (CSF) pressure. Focal and diffuse pachymeningeal enhancement can also be attributed to infectious or inflammatory, neoplastic and iatrogenic aetiologies. Correction of the underlying pathology often results in spontaneous resolution of the pachymeningeal enhancement. There have also been reports of pachymeningeal enhancement associated with cerebral venous sinus thrombosis, temporal arteritis, baroreceptor reflex failure syndrome and arteriovenous fistulae. PMID- 26264064 TI - Therapeutic Hypothermia After Resuscitation From a Non-Shockable Rhythm Improves Outcomes in a Regionalized System of Cardiac Arrest Care. AB - OBJECTIVE: Therapeutic hypothermia (TH) improves neurologic outcome in patients resuscitated from ventricular fibrillation. The purpose of this study was to evaluate TH effects on neurologic outcome in patients resuscitated from a non shockable out-of-hospital cardiac arrest rhythm. DESIGN AND SETTING: This is a retrospective cohort study of data reported to a registry in an emergency medical system in a large metropolitan region. Patients achieving field return of spontaneous circulation are transported to designated hospitals with TH protocols. PATIENTS: Patients with an initial non-shockable rhythm were identified. Patients were excluded if awake in the Emergency Department or if TH was withheld due to preexisting coma or death prior to initiation. The decision to initiate TH was determined by the treating physician. MEASUREMENTS: The primary outcome was survival with good neurologic outcome defined by a cerebral performance category of 1 or 2. MAIN RESULTS: Of the 2772 patients treated for cardiac arrest during the study period, there were 1713 patients resuscitated from cardiac arrest with an initial non-shockable rhythm and 1432 patients met inclusion criteria. The median age was 69 years [IQR 59-82]; 802 (56%) male. TH was induced in 596 (42%) patients. Survival with good neurologic outcome was 14% in the group receiving TH, compared with 5% in those not treated with TH (risk difference = 8%, 95% CI 5-12%). The adjusted OR for a CPC 1 or 2 with TH was 2.9 (95% CI 1.9-4.4). CONCLUSION: Analyzing the data collected from the registry of the standard practice in a large metropolitan region, TH is associated with improved neurologic outcome in patients resuscitated from initial non-shockable rhythms in a regionalized system for post-resuscitation care. PMID- 26264065 TI - Relationship Between Cardiac Dysfunction and Cerebral Perfusion in Patients with Aneurysmal Subarachnoid Hemorrhage. AB - INTRODUCTION: Cardiac dysfunction may occur after aneurysmal subarachnoid hemorrhage (aSAH). Although it is associated with poor outcome, the pathophysiological mechanism of this association remains unclear. We investigated the relationship between cardiac function and cerebral perfusion in patients with aSAH. METHODS: We studied 72 aSAH patients admitted within 72 h after ictus with echocardiography and cerebral CT perfusion within 24 h after admission. Cardiac dysfunction was defined as myocardial wall motion abnormalities or positive troponin. In patients with and without cardiac dysfunction, we calculated the mean perfusion [cerebral blood flow (CBF) and time-to-peak (TTP)] in standard regions of interest and calculated differences with 95% confidence intervals (95% CI). RESULTS: In 35 patients with cardiac dysfunction minimal CBF was 15.83 mL/100 g/min compared to 18.59 in 37 without (difference of means -2.76; 95% CI 5.43 to -0.09). Maximal TTP was 26.94 s for patients with and 23.10 s for patients without cardiac dysfunction (difference of means 3.84; 95% CI 1.63 6.05). Mean global CBF was 21.71 mL/100 g/min for patients with cardiac dysfunction and 24.67 mL/100 g/min for patients without cardiac dysfunction ( 2.96; 95% CI -6.19 to 0.27). Mean global TTP was 25.27 s for patients with cardiac dysfunction and 21.26 for patients without cardiac dysfunction (4.01; 95% CI 1.95-6.07). CONCLUSION: aSAH patients with cardiac dysfunction have decreased focal and global cerebral perfusion. Further studies should evaluate whether this relation is explained by a direct effect of cardiac dysfunction on cerebral circulation or by an external determinant, such as a hypercatecholaminergic or hypometabolic state, influencing both cardiac function and cerebral perfusion. PMID- 26264066 TI - SSRI/SNRI Use is Not Associated with Increased Risk of Delayed Cerebral Ischemia After aSAH. AB - BACKGROUND: To determine the effect of selective serotonin reuptake inhibitor (SSRI)/selective norepinephrine reuptake inhibitor (SNRI) use on the risk of symptomatic vasospasm and delayed cerebral ischemia (DCI) in patients hospitalized with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Retrospective review of consecutive patients with aSAH at Mayo Clinic, Rochester from January 2001 to December 2013. The variables collected and analyzed included age, sex, SSRI/SNRI use, active smoking, transfusion, modified Fisher score, WFNS grade, and outcome at discharge. Multivariate logistic regression analysis was used to evaluate factors associated with DCI, symptomatic vasospasm, and poor outcome (modified Rankin score 3-6) within 1 year. RESULTS: 579 [females 363 (62.7%)] patients with a median age of 55 (IQR 47-65) years were admitted with aSAH during the study period. WFNS at nadir was IV-V in 240 (41.5%), and modified Fisher score was 3-4 in 434 (75.0%). 81 (13.9%) patients had been prescribed an SSRI or SNRI prior to admission and all continued to receive these medications during hospitalization. Symptomatic vasospasm was present in 154 (26.4%), radiological infarction in 172 (29.5%), and DCI in 250 (42.9%) patients. SSRI/SNRI use was not associated with the occurrence of DCI (p = 0.458), symptomatic vasospasm (p = 0.097), radiological infarction (p = 0.972), or poor functional outcome at 3 months (p = 0.376). CONCLUSIONS: The use of SSRI/SNRI prior to and during hospitalization is not associated with DCI or functional outcome in patients with aSAH. PMID- 26264067 TI - Nitric oxide stimulates early egress of Toxoplasma gondii tachyzoites from Human foreskin fibroblast cells. AB - BACKGROUND: Egress is a vital step in the life cycle of Toxoplasma gondii which attracts attentions of many groups. Previous studies have shown that exogenous nitric oxide (NO) stimulates the early egress of T. gondii from infected peritoneal macrophages, a kind of immune cells. However, because Toxoplasma forms cysts in brain and muscle tissues, the development of autonomous immunity in non immune cells is vital for limiting parasite burden and cyst formation. Therefore, we attempted to investigate whether exogenous NO could induce the early egress of T. gondii from infected non-immune cells. METHODS: T. gondii tachyzoites were cultured in human foreskin fibroblast (HFF) cells and were then treated with NO released by sodium nitroferricyanide (III) dihydrate (SNP). The egressed parasites were analysed by flow cytometry. RESULTS: The results showed that NO induced the early egress of parasites from HFF cells before completing their intracellular life cycles. We also found that the occurrence of egress was dependent on intracellular calcium (Ca(2+)) levels and the mobility of the parasite. Compared with freshly isolated tachyzoites, the developmental ability and virulence of egressed tachyzoites presented no difference. CONCLUSIONS: Taken together, our findings demonstrate a novel assay for the analysis of egress signalling mechanisms and an avenue of parasite clearance by hosts of T. gondii. PMID- 26264068 TI - Letter of response to "Individualization of deep brain stimulation targets for movement disorders". PMID- 26264070 TI - Isolated unilateral chemosis with superior forniceal conjunctiva prolapse following frontal craniotomy. PMID- 26264069 TI - Growth stabilization and regression of meningiomas after discontinuation of cyproterone acetate: a case series of 12 patients. AB - BACKGROUND: The relationship between meningiomas and exogenous sex hormones is well known, but cyproterone acetate (CA), a progesterone agonist, seems to have a stronger influence on tumor growth. OBJECTIVE: To show the close relationship between CA treatment and meningioma growth. METHODS: Since 2010, all patients referred to our clinic for a suspicion of meningioma were questioned specifically about exogenous sex hormone intake and more specifically about CA intake. Twelve patients harboring one or multiple meningiomas and treated with CA were identified. CA was stopped in all cases. Tumor volumes and diameters were measured on serial MRIs and compared to the last MRI before CA withdrawal. RESULTS: Ten patients with multiple tumors had been taking the drug for a longer period of time (mean of 20.4 years) than the two patients with one tumor (10 years). Two patients with multiple tumors underwent surgery because of rapidly decreased visual acuity at the time of diagnosis. Discontinuation of CA led to tumor shrinkage in 11 patients and a stop in tumor growth in one [mean tumor volume reduction was around 10 cm(3)/year; range (0.00; 76)]. There was no regrowth during a mean follow-up period of 12 months (range: 5-35). CONCLUSION: For patients diagnosed with a meningioma and treated with CA, medication withdrawal followed by observation should be the first line of treatment. Care should be taken with long-term use of high doses of CA, and serial brain MRIs should be considered after several years of CA. PMID- 26264071 TI - Subdural effusion in decompressive craniectomy. PMID- 26264072 TI - Roles of silkworm endoplasmic reticulum chaperones in the secretion of recombinant proteins expressed by baculovirus system. AB - Baculovirus expression vector system (BEVS) is widely used for production of recombinant eukaryotic proteins in insect larvae or cultured cells. BEVS has advantages over bacterial expression system in producing post-translationally modified secreted proteins. However, for some unknown reason, it is very difficult for insects to secrete sufficiently for certain proteins of interest. To understand the reasons why insect cells fail to secrete some kinds of recombinant proteins, we here employed three mammalian proteins as targets, EPO, HGF, and Wnt3A, with different secretion levels in BEVS and investigated their mRNA transcriptions from the viral genome, subcellular localizations, and interactions with silkworm ER chaperones. Moreover, we observed that no significantly influence on the secretion amounts of all three proteins when depleting or overexpressing most endogenous ER chaperone genes in cultured silkworm cells. However, among all detected ER chaperones, the depletion of BiP severely decreased the recombinant protein secretion in BEVS, indicating the possible central role of Bip in silkworm secretion pathway. PMID- 26264074 TI - Role of multi-modality therapy in peritoneal carcinomatosis and visceral metastasis: a case report and review of the literature. AB - INTRODUCTION: Treatment for advanced stage colorectal cancer with synchronous peritoneal carcinomatosis (PC) and hepatic metastasis (HM) has progressed significantly over the past 10 years. CASE REPORT: We present the case of a 39 year-old female patient with stage IV colorectal cancer with bilateral HM, pulmonary oligometastatic disease, and diffuse PC who underwent hyperthermic intraperitoneal chemotherapy (HIPEC) and complete cytoreductive surgery (CRS) for her intra-abdominal disease. The patient had an uneventful immediate post operative recovery, and subsequently tolerated multiple cycles of adjuvant chemotherapy and percutaneous radiofrequency ablation of pulmonary lesions. At her 22-month follow-up assessment, the patient remains alive with disease. CONCLUSION: Current recommendations for surgical management of synchronous colorectal cancer PC and HM indicate that patients with less than three HMs, a low peritoneal cancer index (PCI), and good functional status will benefit most from CRS and HIPEC. Our patient had an elevated PCI of 12 as measured by computed tomography imaging, and five HMs (all less than 3 cm in size); however, given that her life expectancy on systemic chemotherapy was estimated to be approximately 12 months, we have observed carefully selected patients to benefit from an aggressive multi-modality approach. This case report demonstrates an all too common scenario for surgeons managing patients with advanced CRC, and highlights the importance of patient selection for surgical management as part of multidisciplinary cancer care in this patient population. PMID- 26264073 TI - Combined therapeutic efficacy of carvacrol and X-radiation against 1,2-dimethyl hydrazine-induced experimental rat colon carcinogenesis. AB - Colon cancer is one of the most commonly diagnosed cancers, and is a major cause of cancer morbidity and mortality worldwide. The objective of the present study is to evaluate the combined therapeutic efficacy of carvacrol (CVC) and X radiation against 1,2-dimethylhydrazine-induced colon cancer. Male albino Wistar rats were randomly divided into six groups. Group 1 served as control; group 2 received 40 mg/kg b.wt of CVC orally everyday throughout the experimental period (32 weeks); groups 3-6 received subcutaneous injections of DMH (20 mg/kg b.wt), once a week for the first 15 weeks; group 4 received a single dose of X-radiation at the 31st week; group 5 received CVC (40 mg/kg b.wt) two days after the last injection of DMH and continued everyday till the end of the experimental period; group 6 received CVC as in group 5 and radiation as in group 4. DMH-treated rats showed increased incidence of aberrant crypt foci (ACF), dysplastic aberrant crypt foci (DACF), mast cell number, argyrophilic nucleolar organizer regions; elevated activities of phase I enzymes, decreased activities of phase II enzymes, decreased mucin content and altered colonic and liver histology as compared to control rats. Though the individual treatments with CVC and X-radiation to DMH treated rats reversed the above changes, the combined treatment with both CVC and X-radiation showed a marked effect. Our findings emphasize the potential role of combined therapeutic effect of CVC and X-radiation against DMH-induced colon carcinogenesis. PMID- 26264075 TI - Thymoquinone Anticancer Discovery: Possible Mechanisms. AB - Medicinal plants are known for their many advantages, including the ability to treat diseases such as cancer. Nigella sativa and its active constituent thymoquinone (TQ) have long been used in traditional medicine for treating various conditions related to the respiratory and gastrointestinal systems as well as breast, colorectal, gastric, hepatic, pancreatic cancers and leukemia. TQ has been documented to possess chemo-preventive and chemotherapeutic antitumor effects. Studies reported that TQ inhibits the growth of cancer cells in animal models and culture tumors. This review summarizes the in vitro and in vivo possible mechanisms of TQ anticancer effect. PMID- 26264076 TI - Convenient synthesis and application of versatile nucleic acid lipid membrane anchors in the assembly and fusion of liposomes. AB - Hydrophobic moieties like lipid membrane anchors are highly demanded modifications for nucleic acid oligomers. Membrane-anchor modified oligonucleotides are applicable in biomedicine leading to new delivery strategies as well as in biophysical investigations towards the assembly and fusion of liposomes or the construction of DNA origami structures. We present herein the synthesis and applications of versatile lipid membrane anchor building blocks suitable for solid-supported oligonucleotide synthesis. These are readily synthesized in bulk in five to seven steps from commercially available precursors and can be incorporated at any position within an oligonucleotide without significantly altering the duplex stability and structure as was proven by thermal denaturation experiments and circular dichroism. Furthermore, their applicability could be demonstrated by the assembly and fusion of liposomes mediated by lipid-modified oligonucleotides. PMID- 26264077 TI - Non-innocent adsorption of Co-pyrphyrin on rutile(110). AB - Solar-light driven water splitting is a promising way for the sustainable production of molecular hydrogen, the latter representing an efficient carrier for energy storage and conversion into common liquid fuels. In search of novel catalysts for high-performance water splitting devices, Co-pyrphyrin (CoPy) has been recently synthesized and successfully used as a homogeneous water reduction catalyst. We investigate the adsorption of this molecule on the rutile TiO2(110) surface as a possible first step towards the design of a heterogeneous water reduction system. We find that the adsorption of the molecule is stabilized by the interaction of the cyano groups with the under-coordinated Ti centers present at the surface. This interaction induces the rehybridization of the molecular orbitals localized on the cyano groups and the realignment of the lowest unoccupied molecular states. Moreover, the highest occupied molecular orbital of CoPy@rutile(110) is localized on CoPy and the energy gap turns out to be significantly smaller than the gap of pristine rutile(110). This implies that direct or indirect injection of electrons from CoPy to the rutile(110) surface is in principle possible upon the absorption of light in the visible range. On the other hand, the electronic properties of the Co(ii) center are not modified by the adsorption, which suggests that CoPy and its derivatives may be used in water electrolysis for hydrogen production also in the adsorbed state. PMID- 26264078 TI - Spatial correlations of elementary relaxation events in glass-forming liquids. AB - The dynamical facilitation scenario, by which localized relaxation events promote nearby relaxation events in an avalanche process, has been suggested as the key mechanism connecting the microscopic and the macroscopic dynamics of structural glasses. Here we investigate the statistical features of this process via numerical simulations of a model structural glass. First we show that the relaxation dynamics of the system occurs through particle jumps that are irreversible, and that cannot be decomposed in smaller irreversible events. Then we show that each jump does actually trigger an avalanche. The characteristics of this avalanche change upon cooling, suggesting that the relaxation dynamics crossovers from a noise dominated regime, where jumps do not trigger other relaxation events, to a regime dominated by the facilitation process, where a jump triggers more relaxation events. PMID- 26264079 TI - Supramolecular nanofibers of self-assembling peptides and proteins for protein delivery. AB - We report an efficient strategy for intracellular protein delivery by co assembled supramolecular nanofibers of peptides and proteins. PMID- 26264081 TI - Where to publish. PMID- 26264080 TI - Protease Activity and Cell-Free DNA in Blood Plasma of Healthy Donors and Breast Cancer Patients. AB - Tumor development is generally accompanied by increased protease activity and cell-free DNA (cfDNA) levels in the blood. An immunoassay for protease activity was developed based on the binding of anti-peptide antibodies onto polystyrene plates, followed by incubation with peptides and protein hydrolyzing enzymes. The data obtained demonstrate the peptide CD34-1 composed of uncharged amino acids was the best substrate for the estimation of plasma protease activity in breast cancer patients and healthy donors. Anti-CD34-1 peptide protease activity was shown to correlate with circulating DNA concentrations in cancer patients and healthy subjects (P = 0.001, r = 0.676), demonstrating the role of protease activity in the regulation of cfDNA levels. PMID- 26264082 TI - Delayed healing of lower limb fractures with bisphosphonate therapy. AB - INTRODUCTION: Bisphosphonate therapy (BT) is used commonly in the management of osteoporosis. A systematic review was conducted investigating delayed union of lower limb, long bone fractures in patients on BT. We specifically assessed whether BT increases the risk of delayed union or non-union in lower limb, long bone fractures. METHODS: A literature search was conducted in the PubMed and EmbaseTM on 4 November 2014. Articles that investigated lower limb fractures, history of BT and fracture union were included in the review. RESULTS: A total of 9,809 papers were retrieved and 14 were deemed suitable for this review. The mean time to union in patients on BT was 8.5 months. A longer time to union was reported in a study investigating BT users versus controls (6.5 vs 4.8 months respectively). The mean rate of delayed or non-union for BT associated atypical fractures was 20% per fracture. Specifically in one study, delayed union was more common in the cohort with more than three years of BT (67%) than in the group with less than three years of BT (26%). Surgical fixation was associated with improved outcomes compared with non-operative management. CONCLUSIONS: BT has been described to be associated with multiple adverse outcomes related to atypical fractures. Current evidence recommends operative management for this patient group. Further investigation is required to evaluate the exact effects of BT on lower limb fractures, in particular typical femoral fractures. PMID- 26264083 TI - Small bowel obstruction in pregnancy is a complex surgical problem with a high risk of fetal loss. AB - INTRODUCTION: Small bowel obstruction (SBO) in pregnancy is rare and is most commonly caused by adhesions from previous abdominal surgery. Previous literature reviews have emphasised the need for prompt laparotomy in all cases of SBO because of the significant risks of fetal loss and maternal mortality. We undertook a review of the contemporary literature to determine the optimum management strategy for SBO in pregnancy. METHODS: The MEDLINE(r) and PubMed databases were searched for cases of SBO in pregnancy between 1992 and 2014. Two cases from our own institution were also reviewed. RESULTS: Forty-six cases of SBO in pregnancy were identified, with adhesions being the most common aetiology (50%). The overall risk of fetal loss was 17% and the maternal mortality rate was 2%. In cases of adhesional SBO, 91% of cases were managed surgically, with 14% fetal loss. Two cases (9%) were managed conservatively with no complications. Magnetic resonance imaging (MRI) was used to diagnose SBO in 11% of cases. CONCLUSIONS: Based on our experience and the contemporary literature, we recommend that urgent MRI of the abdomen should be undertaken to diagnose the aetiology of SBO in pregnancy. In cases of adhesional SBO, conservative treatment may be safely commenced, with a low threshold for laparotomy. In other causes, such as volvulus or internal hernia, laparotomy remains the treatment of choice. PMID- 26264084 TI - Laparoscopic splenectomy is emerging 'gold standard' treatment even for massive spleens. AB - INTRODUCTION: Since its first description by Delaitre and Maignien in 1991, laparoscopic splenectomy (LS) has evolved as treatment of choice for mild-to moderately-enlarged spleens and for benign haematological disorders. LS is a challenge if massive spleens or malignant conditions necessitate treatment, but we report our method and its feasibility in this study. METHODS: We undertook a retrospective study of prospectively collected data of all elective splenectomies carried out in our firm of upper gastrointestinal surgeons from June 2003 to June 2012. Only patients opting for elective LS were included in this study. RESULTS: From June 2003 to June 2012, elective splenectomy was carried out in 80 patients. Sixty-seven patients underwent LS and 13 underwent open splenectomy (OS). In the LS group, there were 38 males and 29 females. Age ranged from 6 years to 82 years. Spleen size in the LS group ranged from <=11 cm to 27.6 cm. Twelve patients had a spleen size of >20 cm. Weight ranged from 35 g to 2,400 g. Eighteen patients had a spleen weight of 600-1,600 g and eight had a spleen weight >1,600 g. Operating times were available for 56 patients. Mean operating time for massive spleens was 129.73 min. There was no conversion to OS. There were no major complications. CONCLUSIONS: With improved laparoscopic expertise and advancing technology, LS is safe and feasible even for massive spleens and splenic malignancies. It is the emerging 'gold standard' for all elective splenectomies and has very few contraindications. PMID- 26264085 TI - Acute afferent loop syndrome in the early postoperative period following pancreaticoduodenectomy. AB - INTRODUCTION: Afferent loop syndrome (ALS) is a recognised complication of foregut surgery caused by mechanical obstruction at the gastrojejunostomy anastomosis itself or at a point nearby. Acute ALS has only been reported following pancreaticoduodenectomy (PD) after several years due to recurrence of malignancy at the anastomotic site. We report five cases of acute ALS in the first postoperative week. METHODS: The presentation, clinical findings and successful management of the 5 patients with ALS were obtained from a prospectively collected database of 300 PDs. All five patients with early acute ALS presented with signs and symptoms of a bile leak. Since the fifth patient, the surgical technique has been modified with the creation of a larger window in the transverse mesocolon and a Braun enteroenterostomy. RESULTS: There have been no further incidents of ALS since the adoption of these modifications to the standard technique of PD and there has also been a reduction in postoperative bile leaks (6.4% vs 3.6%, p=0.416). CONCLUSIONS: Acute ALS is a rare but important complication in the immediate postoperative period following PD and causes disruption to adjacent anastomoses, resulting in a bile leak. A prophylactic Braun anastomosis and wide mesocolic window may prevent this complication and subsequent deterioration. PMID- 26264086 TI - The two-port laparoscopic retroperitoneal approach for minimal access pancreatic necrosectomy. AB - INTRODUCTION: Despite advances in surgery and critical care, severe pancreatitis continues to be associated with a high rate of mortality, which is increased significantly in the presence of infected pancreatic necrosis. Controversy persists around the optimal treatment for such cases, with specialist units variously advocating open necrosectomy, simple percutaneous drainage or one of several minimal access approaches. We describe our technique and outcomes with a two-port laparoscopic retroperitoneal necrosectomy (2P-LRN). METHODS: Thirteen consecutive patients with proven infected pancreatic necrosis were treated by 2P LRN over a three-year period in the setting of a specialist hepatopancreatobiliary unit. The median patient age was 46 years (range: 28-87 years) and 10 of the patients were male. RESULTS: The median number of procedures required to clear the necrosis was 2 (range: 1-5), with a median time to discharge following the procedure of 44 days (range: 10-135 days). There was no 90-day mortality and the morbidity rate was 38%, consisting of pancreatic fistula (31%) and bleeding (23%). CONCLUSIONS: Two-port laparoscopic retroperitoneal necrosectomy has been demonstrated to confer similar or better outcomes to other techniques for necrosectomy. It carries the additional advantages of better visualisation, leading to fewer procedures and the opportunity to deploy simple laparoscopic instruments such as diathermy or haemostatic clips. PMID- 26264087 TI - The use of health related quality of life data to produce information sheets for patients with head and neck cancer. AB - INTRODUCTION: Health related quality of life information gives patients and carers an indication of how they will be affected following treatment. Such knowledge can promote realistic expectations and help patients come to terms with their outcome. The aim of this paper is to describe the background development of patient information sheets produced at our unit. METHODS: The data were compiled using a common head and neck cancer specific quality of life questionnaire (University of Washington Quality of Life [UW-QOL]). There are 12 domains comprising activity, appearance, anxiety, chewing, mood, pain, recreation, saliva, shoulder, speech, swallowing and taste. The data were collected over 19 years at our unit and focus on follow-up records at around 2 years as this gives a good indication of health related quality of life in survivorship. UW-QOL questionnaires were available from 1,511 patients treated following primary diagnosis of head and neck cancer, and there were 24 subgroups based on cancer site, stage and treatment. There were 2 other subgroups: 132 having transoral laser resection and 176 having laryngectomy. RESULTS: The patient and carer research forum helped to design the information sheets, which display overall quality of life, percentages with 'good' outcome and 'significant problem' by domain, and the most important domains. Three examples are included in this paper: early stage oral cancer treated by surgery alone, early laryngeal cancer treated by surgery alone, and late stage oropharyngeal cancer treated by surgery and postoperative radiotherapy. All 26 subgroup information sheets are available in booklet form and on the internet. CONCLUSIONS: How the surgical community best utilises this type of resource needs further research. PMID- 26264088 TI - Improving postoperative pain management in subpectoral tissue expander implant reconstruction of the breast using an elastomeric pump. AB - INTRODUCTION: Postoperative pain after breast surgery is one of the major factors contributing to delay in mobilisation and prolonged hospital stay. A retrospective analysis was performed of patients undergoing skin sparing mastectomy and insertion of a subpectoral implant. The aim was to determine whether the use of an elastomeric local anaesthetic pump improved pain control and length of stay. METHODS: Twenty-five consecutive patients undergoing the above procedure were sited with an elastomeric local anaesthetic infusion pump intraoperatively, in addition to standard regular and pro re nata analgesia. The control group comprised 25 patients undergoing the same procedure in the same year who received standard analgesia alone. Visual analogue scale scores were recorded for the duration of inpatient stay, as was any further analgesic requirement. RESULTS: The median age was 51 years (range: 26-75 years) in the intervention group and 50 years (range: 28-70 years) in the control group. The mean visual analogue scale score was 0.28 (standard deviation [SD]: 0.61) at 24 hours for the intervention group and 1.84 (SD: 0.37) for the control group (p<0.0001). The mean length of stay was 1.8 days (SD: 0.71 days) for the intervention group and 2.28 days (SD: 0.94 days) for the control group (p=0.15). There were no complications involving catheter placement, leakage or toxicity relating to use of the local anaesthetic. CONCLUSIONS: There was significantly reduced pain with the use of the local anaesthetic infusion pump. The elastomeric pump is a step towards enhanced patient recovery after breast surgery in the case of skin sparing mastectomy and subpectoral tissue expander reconstruction. PMID- 26264089 TI - Colorectal cancer screening characteristics of patients presenting with symptoms of colorectal cancer and effect on clinical outcomes. AB - INTRODUCTION: National colorectal cancer screening, utilising a faecal occult blood test (FOBT), is now well established in the UK. The aim of this study was to define the screening characteristics of patients presenting to secondary care with symptoms of colorectal cancer and to assess the effect of screening outcome on subsequent symptomatic presentation. METHODS: This was a retrospective analysis of all patients of screening age presenting within one calendar year in a tertiary trust via a two-week wait (2WW) pathway owing to suspicion of colorectal cancer. Colorectal cancer related outcomes were compared between patients in the cohort who had previously accepted bowel cancer screening and patients who had previously declined bowel cancer screening. The primary endpoint was overall incidence of colorectal neoplasia. Secondary endpoints included incidence of colorectal malignancy, cancer related mortality, cancer related outcomes and polyp related outcomes. RESULTS: Overall, 2,227 patients presented via the 2WW pathway; 955 were aged 60-75 years. Among the latter, 411 (43%) had been screened previously and had a negative FOBT, and 544 (57%) had declined screening. Incidence of colorectal neoplasia did not differ between the two groups (113 [27%] vs 143 [26%], p=0.7). Of those with a negative FOBT and subsequent symptomatic presentation, 16 (3.9%) were diagnosed with a colorectal malignancy compared with 36 (6.6%) of those who declined screening and had subsequent symptomatic presentation (relative risk: 1.7, 95% confidence interval: 0.96-3.02, p=0.08). There were no differences between the two groups with regard to TNM (tumour, lymph nodes, metastasis) stage, Dukes' stage, metastases, number of polyps or cancer related mortality (median follow-up duration: 20 months). CONCLUSIONS: The incidence of colorectal neoplasia was similar among patients who previously had a negative FOBT and those who declined screening. There was a higher incidence of colorectal cancer detected among those who declined screening but it did not reach statistical significance. All other cancer and polyp outcomes were similar between the groups. PMID- 26264090 TI - Anterior parasternal approach for creation of a pericardial window. AB - INTRODUCTION: The optimal method for creation of a pericardial window (PW) is still controversial and it remains a surgical challenge, mainly in obese patients. The aim of this study was to evaluate the efficacy and safety of a novel approach that has not been described previously, for creation of a PW in patients with symptomatic, chronic, large pericardial effusion. METHODS: We retrospectively analysed the records of 30 patients (14 men, 16 women) who underwent a PW procedure between 2001 and 2011. The mean age was 63 years (standard deviation [SD]: 17 years, median: 60 years, range: 27-90 years) and the mean body mass index was 34 kg/m(2) (SD: 2 kg/m(2)). The operation was performed through a curvilinear parasternal approach, 6-8 cm in length, followed by a mini thoracotomy between ribs 4 and 5. Discharged patients were followed up clinically. RESULTS: The mean operative time was 73 minutes (SD: 21 minutes) and a median of 658 ml (range: 300-1,500 ml) of fluid was evacuated. The main aetiologies were idiopathic in 17 patients (57%) and malignant in 9 (30%). Seven patients (23%) died in hospital owing to underlying malignancy. Postoperative complications included mild renal failure (20%), respiratory failure (20%), pneumonia (13%), atrial fibrillation (10%) and atelectasis (6%). There were no wound infections. The median length of stay following the procedure was 8 days. In a median follow-up period of 3.8 years, 16 patients with non-malignant effusion were free of recurrence of pericardial effusion. CONCLUSIONS: The anterior parasternal approach for creation of a PW is simple, safe and efficacious, and results in long-term symptomatic improvement, specifically in patients with non-malignant effusions. This approach may be more appealing in obese patients. PMID- 26264091 TI - The incidence of hypomagnesaemia following abdominal aortic aneurysm surgery. AB - INTRODUCTION: Magnesium is important for cardiac function. Hypomagnesaemia is associated with a higher incidence of arrhythmias and poorer outcomes in cardiac surgery. No studies have investigated the incidence or impact of postoperative hypomagnesaemia after abdominal aortic aneurysm (AAA) surgery. We aim to assess the incidence of hypomagnesaemia after AAA repair in our population. METHODS: Retrospective analysis was performed of patients who underwent elective AAA surgery at a single vascular centre. The last 110 patients undergoing open or endovascular AAA repair were identified. The hospital pathology system was used to identify the immediate postoperative serum magnesium levels as well as patient demographics and admission details. Hypomagnesaemia was defined as serum magnesium of <0.7 mmol/l. RESULTS: A total of 211 patients were studied and there were 3 deaths. Of the patients included, 101 underwent open elective AAA repair and 110 underwent endovascular repair. In the elective open repair group, 73 patients (73%) were hypomagnesaemic. In the endovascular repair group, 35 (32%) had hypomagnesaemia. A t-test showed a statistically significant difference in hypomagnesaemia between the open and endovascular groups (p<0.001). CONCLUSIONS: AAA surgery is associated with a high incidence of postoperative hypomagnesaemia, which is significantly greater among open repair patients. This is likely to have an effect on cardiac activity and lead to cardiac complications such as arrhythmias and poorer postoperative outcomes, especially in the open AAA repair subgroup. This stresses the importance of serum magnesium and cardiac monitoring in the postoperative phase. A prospective study is proposed to further investigate these findings, and their potential implications on perioperative morbidity and mortality. PMID- 26264092 TI - A two-year follow-up observational study of the T-14 paediatric throat disorders outcome measure in tonsillectomy and adenotonsillectomy. AB - INTRODUCTION: The T-14 questionnaire is a validated patient reported outcome measure used to assess the value of paediatric tonsillectomy from the patient's perspective. There are currently limited data revealing the long-term postoperative effects of tonsillectomy on quality of life in the paediatric population. A previously published study was therefore extended to provide additional data at 12 and 24 months following surgery. METHODS: A prospective uncontrolled observational study was undertaken examining 54 paediatric patients undergoing tonsillectomy at Portsmouth Hospitals NHS Trust. Parents of children having surgery were invited to complete a T-14 questionnaire preoperatively as well as at 3, 6 (previously published), 12 and 24 months postoperatively. RESULTS: The questionnaire was completed for 50 of the 54 patients preoperatively as well as at 3, 6 and 12 months postoperatively, with 44 being completed at 24 months. The mean difference between the preoperative T-14 scores and the scores at 3, 6, 12 and 24 months following surgery were highly statistically significant (p<0.001). CONCLUSIONS: This is the first study published in the literature to assess the T-14 questionnaire at 12 and 24 months following paediatric tonsillectomy, providing evidence of the ongoing benefit of patient reported outcome measures. This further confirms the value of tonsillectomy in the paediatric population and demonstrates its ongoing positive effects on quality of life. PMID- 26264093 TI - National survey on endoscopy training in the UK. AB - INTRODUCTION: Gastrointestinal (GI) endoscopy is an important skill for both gastroenterologists and general surgeons but concerns have been raised about the provision and delivery of training. This survey aimed to evaluate and compare the delivery of endoscopy training to gastroenterology and surgical trainees in the UK. METHODS: A nationwide electronic survey was carried out of UK gastroenterology and general surgery trainees. RESULTS: There were 216 responses (33% gastroenterologists, 67% surgeons). Gastroenterology trainees attended more non-training endoscopy lists (mean: 3.0 vs 1.2) and training lists than surgical trainees (mean: 0.9 vs 0.5). A significantly higher proportion of gastroenterologists had already achieved accreditation in gastroscopy (60.8% vs 28.9%), colonoscopy (66.7% vs 1.4%) and flexible sigmoidoscopy (33.3% vs 3.0%). More gastroenterology trainees aspired to achieve accreditation in gastroscopy (97.2% vs 79.2%), flexible sigmoidoscopy (91.7% vs 70.1%) and colonoscopy (88.8% vs 55.5%) by completion of training. By completion of training, surgeons were less likely than gastroenterologists to have completed the required number of procedures to gain accreditation in gastroscopy (60.3% vs 91.3%), flexible sigmoidoscopy (64.6% vs 68.6%) and colonoscopy (60.3% vs 70.3%). CONCLUSIONS: This survey highlights marked disparities between surgical and gastroenterology trainees in both aiming for and achieving accreditation in endoscopy. Without changes to the delivery and provision of training as well as clarification of the role of endoscopy training in a surgical training programme, future surgeons will not be able to perform essential endoscopic assessment of patients as part of their management algorithm. PMID- 26264094 TI - Acute appendicitis in the developing world is a morbid disease. AB - INTRODUCTION: Acute appendicitis in the developing world has a markedly different disease profile to that in the developed world. METHODS: A retrospective study was undertaken over a four-year period at a university hospital in South Africa to review the disease spectrum and the clinical outcome of acute appendicitis. RESULTS: A total of 1,004 patients (54% male, median age: 18 years) with intraoperatively confirmed appendicitis were reviewed. Over half (56%) were from the urban district within the city of Pietermaritzburg and the remaining 44% were from the rural health district. The median duration of illness from onset to definitive care was 4 days. Sixty per cent of appendices were perforated and associated with intra-abdominal contamination. Forty per cent of patients required reoperation to control intra-abdominal sepsis. Ten per cent required admission to the intensive care unit. The median overall length of hospital stay was 5 days. The mortality rate was 1%. Rural patients had a longer median duration of illness (3 vs 5 days, p<0.001) as well as a more advanced disease profile associated with perforation and severe intra-abdominal sepsis (19% vs 71%, p<0.001). Female patients had a longer median duration of illness (3 vs 4 days, p<0.001), were more likely to present with severe intra-abdominal sepsis (31% vs 54%, p<0.001) and were more likely to require a laparotomy (50% vs 73%, p<0.001). The total cost of managing the entire cohort of 1,004 patients over the 4-year period was L2,060,972. CONCLUSIONS: Acute appendicitis in South Africa is a serious disease associated with significant morbidity. Late presentation is common. Female and rural patients have the worst clinical outcomes, with significant cost to the health system. PMID- 26264095 TI - 'Rain chain' for ankle arthroscopy. PMID- 26264096 TI - How to 'jimmy' the chest in emergency median sternotomy. PMID- 26264097 TI - Minimally invasive removal of sharp radio-opaque foreign bodies in the foot. PMID- 26264098 TI - A simple transanal technique to complete perineal dissection of a proctectomy when the limits are not visible from above or below. PMID- 26264099 TI - The novel use of the Yankauer sucker as a radiolucent drill guide in orthopaedic surgery. PMID- 26264100 TI - The use of the Explant(r) device in metal backed ExeterTM acetabular component revision. PMID- 26264101 TI - A novel way to augment a tibial prosthesis for significant bone loss. PMID- 26264102 TI - A novel technique to assist arthroscopic screw removal. PMID- 26264103 TI - Technical tip in the use of obstetric forceps to remove high rectal foreign bodies. PMID- 26264104 TI - Albarran deflecting bridge: an aid to intra-detrusor injection of botulinum toxin. PMID- 26264105 TI - The treatment of deep infection by intraoperative manufacture of removable, antibiotic impregnated bead strings. PMID- 26264106 TI - Brunner's gland hamartoma of the duodenum. AB - Brunner's gland hamartoma (BGH) is a rare benign tumour of the duodenum. We present a case of duodenal obstruction caused by a BGH, which required surgical resection after a failed attempt at endoscopic removal. PMID- 26264107 TI - A combined vascular surgical and clinical genetics approach to diffuse aneurysmal disease. AB - We report two patients who presented with extensive aneurysmal disease, in association with minimal external physical signs. Patient 1 remained genetically undiagnosed despite multiple structural, biochemical and genetic investigations. He made a good recovery following surgery for popliteal and left axillary artery aneurysms. Patient 2 was diagnosed with vascular type Ehlers-Danlos syndrome, associated with a high degree of tissue and blood vessel fragility, and is being managed conservatively. Early multidisciplinary assessment of such patients facilitates accurate diagnosis and management. PMID- 26264108 TI - A diaphragmatic retroperitoneal cyst. AB - Diaphragmatic lesions are usually congenital bronchogenic cysts. A patient with a known diaphragmatic cyst presented with new onset right upper quadrant pain. Repeat imaging showed enlargement of the cyst, the CA19-9 cancer marker was raised at 312 iu/ml (normal: <27 iu/ml) and positron emission tomography combined with computed tomography showed focally increased uptake in the cystic wall. In view of symptoms and risk of neoplasia, the lesion was excised. Histology showed a benign epidermoid cyst. Features falsely suggesting neoplasia have been reported previously with benign splenic cysts but not with a benign diaphragmatic epidermoid cyst. PMID- 26264109 TI - A case of small-bowel obstruction after insertion of a percutaneous endoscopic gastrostomy tube due to mesenteric penetration. AB - A case of small-bowel obstruction after insertion of a percutaneous endoscopic gastrostomy (PEG) tube is described. At laparotomy, the PEG tube was found to have penetrated the jejunal mesentery at two points, thereby acting as a focus for a volvulus. Direct injury and obstruction to the small bowel have been described but volvulus due to mesenteric penetration has not. PMID- 26264110 TI - Epidural abscess with associated spondylodiscitis following prostatic biopsy. AB - Spondylodiscitis is often iatrogenic in nature. We report the case of a 69-year old man presenting with spondylodiscitis and associated epidural abscess following transrectal ultrasonography guided prostate biopsy despite ciprofloxacin cover. To our knowledge, this is the first case of spondylodiscitis secondary to fluoroquinolone resistant Escherichia coli. PMID- 26264113 TI - Friction coefficient analysis during high-heeled gait. PMID- 26264111 TI - An undigested cherry tomato as a rare cause of small bowel obstruction. AB - Small bowel obstruction due to undigested fibre from fruits and vegetables is a rare but known medical condition. We report a case of small bowel obstruction caused by a whole cherry tomato in a patient without a past medical history of abdominal surgery. A 66-year-old man presented to the emergency department complaining of lower abdominal pain with nausea and vomiting. His last bowel movement had occurred on the morning of presentation. He underwent abdominal computed tomography (CT), which showed a sudden change of diameter in the distal ileum with complete collapse of the proximal small bowel segment. Laparoscopy confirmed a small bowel obstruction with a transition point close to the ileocaecal valve. An enterotomy was performed and a completely undigested cherry tomato was retrieved. To our knowledge, this is the first reported case of a small bowel obstruction caused by a whole cherry tomato. PMID- 26264114 TI - Sequence-dependent rotation axis changes and interaction torque use in overarm throwing. AB - We examined the role of rotation axes during an overarm throwing task. Participants performed such task and were asked to throw a ball at maximal velocity at a target. The purpose of this study was to examine whether the minimum inertia axis would be exploited during the throwing phases, a time when internal-external rotations of the shoulder are particularly important. A motion capture system was used to evaluate the performance and to compute the potential axes of rotation (minimum inertia axis, shoulder-centre of mass axis and the shoulder-elbow axis). More specifically, we investigated whether a velocity dependent change in rotational axes can be observed in the different throwing phases and whether the control obeys the principle of minimum inertia resistance. Our results showed that the limbs' rotational axis mainly coincides with the minimum inertia axis during the cocking phase and with the shoulder-elbow axis during the acceleration phase. Besides these rotation axes changes, the use of interaction torque is also sequence-dependent. The sequence-dependent rotation axes changes associated with the use of interaction torque during the acceleration phase could be a key factor in the production of hand velocity at ball release. PMID- 26264116 TI - Combatting bacterial persister cells. AB - Most bacterial cells lead lives of quiet desperation in biofilms, combatting stress; yet, their prevalence attests to their ability to alter gene regulation to cope with myriad insults. Since biofilm bacteria are faced with starvation and other environmental stress (e.g., antibiotics from competitors, oxidative stress from host immune systems), it behooves them to be able to ramp down their metabolism in a highly regulated manner and enter a resting state known as persistence to weather stress. Hence, persister cells are metabolically dormant cells that arise predominantly as a response to stress through elegant gene regulation that includes toxin/antitoxin systems. In this review, an analysis is made of the genetic pathways that lead to persistence, of cell signaling via the interspecies and interkingdom signal indole that leads to persistence, and the means found to date for combatting these cells which are frequently tolerant to a range of antibiotics. PMID- 26264115 TI - Genetic variants of numb gene were associated with elevated total cholesterol level and low density lipoprotein cholesterol level in Chinese subjects, in Xinjiang, China. AB - BACKGROUND: Hypercholesterolemia is one of the most common risk factors for Coronary Artery Disease (CAD), which is the leading cause of death worldwide. As Numb is an important regulating factor regarding intestinal cholesterol absorption and plasma cholesterol level, the aim of the present study is to investigate the relationship between human Numb gene polymorphism and cholesterol level in Chinese subjects. METHODS: All participants came from the First Affiliated Hospital of Xinjiang Medical University (Male: 1052 and Female: 596), and four tagging SNPs (rs2108552, rs12435797, rs1019075 and rs17781919) of Numb gene were genotyped by using TaqMan assays and analyzed in an ABI 7900HT Fast Real-Time PCR System. Further, general liner model was applied for assessing the relationship between cholesterol level and genotypes. RESULTS: By analyzing a dominant model, recessive model and an additive model, we have found that SNP rs2108552 was associated with total cholesterol (TC) and low density lipoprotein cholesterol level (LDL-C) (P = 0.000 and P = 0.007; P =0.042 and P =0.009; P = 0.006 and P = 0.030). C allele of SNP rs17781919 had significantly lower plasma TC level (3.46 +/- 0.74 mmol/L vs 4.27 +/- 1.1 mmol/L) and LDL-C level (0.98 +/- 0.55 mmol/L vs 2.64 +/- 0.93 mmol/L) when compared with T allele. Additionally, SNP rs12435797 was associated with TC level and SNP rs1019075 was associated with LDL-C level by analyses of a dominant model, recessive model and an additive model (P = 0.000, P = 0.005 and P = 0.004; P = 0.016, P = 0.008 and P = 0.033). Further, the association of rs2108552, rs12435797, rs1019075 and rs17781919 with aforementioned different kinds of cholesterol levels remained statistically significant after multivariate adjustment of ethnicity, gender, age, smoking and obesity. CONCLUSIONS: Our results indicated that both rs2108552 and rs17781919 in the Numb gene were associated with total cholesterol level and density lipoprotein-cholesterol level in Chinese subjects. PMID- 26264117 TI - Systematic Review of Preventive and Acute Treatment of Menstrual Migraine. AB - OBJECTIVE: The aim of this systematic review is to identify the efficacy of different categories of treatments for menstrual migraines as found in randomized controlled trials or open label studies with similar efficacy endpoints. BACKGROUND: Menstrual migraine is very common and approximately 50% of women have increased risk of developing migraines related to the menstrual cycle. Attacks of menstrual migraine are usually more debilitating, of longer duration, more prone to recurrence, and less responsive to acute treatment than nonmenstrual migraine attacks. METHODS: Search for evidence was done in 4 databases that included PubMed, EMBASE, Science Direct, and Web of Science. Eighty-four articles were selected for full text review by 2 separate readers. Thirty-six of the 84 articles were selected for final inclusion. Articles included randomized controlled and open label trials that focused on efficacy of acute and preventative therapies for menstrual migraine. Secondary analyses where excluded because the initial study population was not women with menstrual migraine. RESULTS: After final screening, 11 articles were selected for acute and 25 for preventive treatment of menstrual migraine. These were further subdivided into treatment categories. For acute treatment: triptans, combination therapy, prostaglandin synthesis inhibitor, and ergot alkaloids. For preventive treatment: triptans, combined therapy, oral contraceptives, estrogen, nonsteroidal anti inflammatory drug, phytoestrogen, gonadotropin-releasing hormone agonist, dopamine agonist, vitamin, mineral, and nonpharmacological therapy were selected. Overall, triptans had strong evidence for treatment in both acute and short term prevention of menstrual migraine. CONCLUSIONS: Based on this literature search, of all categories of treatment for menstrual migraine, triptans have the most extensive research with strong evidence for both acute and preventive treatment of menstrual migraine. Further randomized controlled trials should be performed for other therapies to strengthen their use in the care of menstrual migraine patients. PMID- 26264118 TI - Sequential sampling: a novel method in farm animal welfare assessment. AB - Lameness in dairy cows is an important welfare issue. As part of a welfare assessment, herd level lameness prevalence can be estimated from scoring a sample of animals, where higher levels of accuracy are associated with larger sample sizes. As the financial cost is related to the number of cows sampled, smaller samples are preferred. Sequential sampling schemes have been used for informing decision making in clinical trials. Sequential sampling involves taking samples in stages, where sampling can stop early depending on the estimated lameness prevalence. When welfare assessment is used for a pass/fail decision, a similar approach could be applied to reduce the overall sample size. The sampling schemes proposed here apply the principles of sequential sampling within a diagnostic testing framework. This study develops three sequential sampling schemes of increasing complexity to classify 80 fully assessed UK dairy farms, each with known lameness prevalence. Using the Welfare Quality herd-size-based sampling scheme, the first 'basic' scheme involves two sampling events. At the first sampling event half the Welfare Quality sample size is drawn, and then depending on the outcome, sampling either stops or is continued and the same number of animals is sampled again. In the second 'cautious' scheme, an adaptation is made to ensure that correctly classifying a farm as 'bad' is done with greater certainty. The third scheme is the only scheme to go beyond lameness as a binary measure and investigates the potential for increasing accuracy by incorporating the number of severely lame cows into the decision. The three schemes are evaluated with respect to accuracy and average sample size by running 100 000 simulations for each scheme, and a comparison is made with the fixed size Welfare Quality herd-size-based sampling scheme. All three schemes performed almost as well as the fixed size scheme but with much smaller average sample sizes. For the third scheme, an overall association between lameness prevalence and the proportion of lame cows that were severely lame on a farm was found. However, as this association was found to not be consistent across all farms, the sampling scheme did not prove to be as useful as expected. The preferred scheme was therefore the 'cautious' scheme for which a sampling protocol has also been developed. PMID- 26264119 TI - Esophagogastric junction distensibility in the management of achalasia patients: relation to treatment outcome. AB - BACKGROUND: Achalasia is characterized by a functional esophagogastric junction (EGJ) obstruction. The functional luminal imaging probe (EndoFLIP) is a method to assess EGJ distensibility. In a homogeneous group of newly diagnosed achalasia patients treated with pneumatic dilation (PD), we aimed (i) to determine whether the assessment of EGJ distensibility has added value in the management of achalasia patients and (ii) to evaluate whether EGJ distensibility differs between achalasia subtypes. METHODS: Twenty-six newly diagnosed achalasia patients were treated by graded PD (30 and 35 mm) separated by 1 week. EGJ distensibility was measured with the EndoFLIP technique before and after 30 mm PD. Good clinical outcome was defined as an Eckardt score <4 at 1-year follow-up. Fifteen healthy controls underwent an EndoFLIP measurement as control group. KEY RESULTS: Newly diagnosed achalasia patients had reduced EGJ distensibility compared to healthy controls (0.9 [0.7-1.5] vs 3.4 [2.7-4.2] mm(2) /mmHg, p < 0.01), and EGJ distensibility was lower in type II compared to type I patients (0.8 [0.7-1.1] vs 1.5 [0.9-1.9] mm(2) /mmHg, p = 0.02). EGJ distensibility was increased after PD from 0.9 (0.7-1.5) to 4.2 (3.0-5.7) mm(2) /mmHg (p < 0.001). No difference was found in EGJ distensibility directly after PD between patients with good and poor clinical outcome at 1-year follow-up. CONCLUSIONS & INFERENCES: Assessment of EGJ distensibility with the EndoFLIP technique is able to demonstrate the functional EGJ obstruction in newly diagnosed achalasia patients and EGJ distensibility differs between achalasia subtypes. Although PD improves EGJ distensibility, assessment of EGJ distensibility with a limited number of distension steps provides no additional information that is useful for clinical evaluation and management of achalasia patients. PMID- 26264120 TI - Discriminating different causes of transfusion-associated pulmonary edema. PMID- 26264122 TI - Assisted reproductive technology: an uncommon, but increasing, cause of parent child ABO discrepancy. PMID- 26264123 TI - Efficacy of education as an intervention to reduce red blood cell utilization: the importance of a precise description of what is meant by "education". PMID- 26264124 TI - Evaluation of "Transfusion Camp," a postgraduate transfusion medicine education program using the BEST-TEST knowledge assessment tool. PMID- 26264125 TI - ERRATUM. PMID- 26264127 TI - The clinical utility of naturalistic action test in differentiating mild cognitive impairment from early dementia in memory clinic. AB - OBJECTIVE: This study aimed to examine the validity of the Naturalistic Action Test in differentiating Mild Cognitive Impairment from early dementia compared to clinical diagnosis and ascertain Naturalistic Action Test cut-off points. METHODS: This was a cross-sectional study of 70 consecutive patients diagnosed with Mild Cognitive Impairment attending the memory clinic in St James's Hospital, Dublin, Ireland. Patients with a diagnosis of Mild Cognitive Impairment who attended for routine annual assessment were asked to participate in the study. The Naturalistic Action Test was carried out after the patient had completed their routine assessment in the clinic. RESULTS: The Area under the Curve, AUC +/- SE was 0.808 +/- 0.058, p < 0.001 with 95% CI (0.695-0.922). There was concordance in 40 and discrepancy in 30 patients between the NAT and the gold standard consensus diagnosis (PPV 38%, NPV 96%, sensitivity 94%, specificity 46% and accuracy 59%) using cut-off point of >=14 for normal function on Naturalistic Action Test. The difference was not related to age, sex, level of education or informant. Using the Youden index, we determined a Naturalistic Action Test cut off score of >=11 for Mild Cognitive Impairment in our study (PPV 50%, NPV 91%, sensitivity 78%, specificity 73% and accuracy of 74%). There was discrepancy in 18 patients using the new cut-off point (>=11 for Mild Cognitive Impairment vs <=10 for dementia). CONCLUSION: The Naturalistic Action Test is a useful tool that can increase diagnostic accuracy in differentiating Mild Cognitive Impairment from early dementia. PMID- 26264128 TI - Preparing the next generation of genomicists: a laboratory-style course in medical genomics. AB - The growing gap between the demand for genome sequencing and the supply of trained genomics professionals is creating an acute need to develop more effective genomics education. In response we developed "Practical Analysis of Your Personal Genome", a novel laboratory-style medical genomics course in which students have the opportunity to obtain and analyze their own whole genome. This report describes our motivations for and the content of a "practical" genomics course that incorporates personal genome sequencing and the lessons we learned during the first three iterations of this course. PMID- 26264129 TI - Individual and collective empowerment and associated factors among Brazilian adults: a cross-sectional study. AB - BACKGROUND: The empowerment embedded in the health area is defined as a process that can facilitate control over the determinants of health of individuals and population as a way to improve health. The aim of this study was to verify the association between individual and collective empowerment with sociodemographic conditions, lifestyle, health conditions and quality of life. METHOD: A cross sectional analytical study was conducted with 1150 individuals (aged 35 to 44 years). The empowerment was determined by questions from the Integrated Questionnaire for the Measurement of Social Capital (IQ-MSC). The quality of life was measured using the WHOQOL (World Health Organization Quality of Life-Bref). Lifestyle and health conditions were obtained by adapted questions from the Fantastic Lifestyle Questionnaire The DMFT Index was incorporated in the health conditions questions. Logistic regression or multinomial regression was performed. RESULTS: The practice of physical activity was related to individual (OR: 2.70) and collective (OR: 1.57) empowerment. Regarding individual empowerment, people with higher education level (5-11 years - OR: 3.46 and >=12 years - OR: 4.41), who felt more able to deal with stress (OR:3.76), who presented a high score on quality of life (psychological domain) (OR:1.23) and that smoked (OR:1.49) were more likely to feel able to make decisions and participate in community activities. The increase in the DMFT Index represented less chance of individuals to feel more able to make decisions (OR: 0.96). Regarding the collective empowerment, being religious (catholic) (OR: 1.82), do not drink or drink just a little (OR: 1.66 and 2.28, respectively), and increased score of overall quality of life (OR: 1.08) were more likely to report that people cooperate to solve a problem in their community. CONCLUSION: The two approaches to empowerment, the individual and collective are connected, and the physical activity showed to be a good strategy for the empowerment construction. PMID- 26264130 TI - Increased number of structured diabetes education attendance was not associated with the improvement in patient-reported health-related quality of life: results from Patient Empowerment Programme (PEP). AB - AIMS: To assess the effect of a structured education intervention, Patient Empowerment Programme (PEP) patient-reported health-related quality of life (HRQOL) among type 2 diabetes mellitus (T2DM) patients, and if positive effect is confirmed, to further explore any association between frequency of sessions attendance and HRQOL. METHODS: A total of 298 T2DM patients were recruited when they attended the first session of PEP, between March and September 2010, and were followed over a one-year period from baseline. HRQOL data were assessed using Short Form-12 Health Survey version 2 (SF-12) and Short Form-6 Dimension (SF-6D) at baseline and one-year follow-up. Individuals' anthropometric and biomedical data were extracted from an administrative database in Hong Kong. Unadjusted and adjusted analyses of linear regression models were performed to examine the impact of PEP session attendance on the change in the HRQOL scores, accounting for the socio-demographic and clinical characteristics at baseline. RESULTS: Of the 298 eligible patients, 257 (86.2%) participated in the baseline assessment and 179 (60.1%) patients completed the follow-up assessment, respectively. Overall, PEP resulted in a significant improvement in SF-12 bodily pain and role emotional subscales and SF-6D utility scores. These positive changes were not associated with the level of participation as shown in both unadjusted and adjusted analyses. CONCLUSIONS: The PEP made significant improvement in bodily pain, role emotional and overall aspects of HRQOL. Higher number of session attendance was not associated with improvement in HRQOL in primary care real-world setting. Key Messages ? Participants with type 2 diabetes mellitus who participated in structured diabetes education programme made significant improvement in bodily pain and role emotional subscales and SF-6D scores. ? There was no association between the number of sessions attended and any aspect of HRQOL. PMID- 26264131 TI - Barriers to cervical cancer screening experienced by lesbian women: a qualitative study. AB - AIMS AND OBJECTIVES: To provide deeper insights into the experiences of lesbian women in accessing cervical cancer screening and to inform strategies to increase the uptake of these services for this group of women. BACKGROUND: Lesbian women continue to face significant health disparities and are at increased risk for specific medical conditions. With cervical cancer being largely a preventable disease, early detection through the Papanicolaou test is crucial, as it enables treatment to commence early and limit the progression of the disease. Although the rates of cervical abnormalities among lesbian women are similar to that of the general population, lesbian women are less likely to have regular cervical screening. The reasons for this are largely unknown and there is a paucity of research that explores cervical cancer screening in lesbian women. DESIGN: Qualitative descriptive design. METHODS: Participants (n = 9) were recruited via media release and those living in New South Wales who self-identified as lesbian, meeting the inclusion criteria were recruited for the study. Semi-structured, face to face and telephone interviews were used to obtain narrative data from lesbian women on their experiences of cervical screening. RESULTS: Three main themes emerged from the data: 'Lack of opportunistic screening'; 'Fear of penetration' and 'Encountering heterosexism and discrimination'. CONCLUSIONS: This current study builds on existing knowledge and further, has identified issues that have not been previously raised in the literature. New findings from this study highlight participants' fear of penetration, and stigma associated with accessing information, as substantial barriers to cervical screening. RELEVANCE TO CLINICAL PRACTICE: This study's findings can guide future research and highlight possibilities for specific strategies to reduce health disparities among lesbian women. PMID- 26264132 TI - The Glutamine-Alanine Repeat Domain of TCERG1 is Required for the Inhibition of the Growth Arrest Activity of C/EBPalpha. AB - TCERG1 was characterized previously as a repressor of the transcription factor C/EBPalpha through a mechanism that involved relocalization of TCERG1 from nuclear speckles to pericentromeric regions. The inhibitory activity as well as the relocalization activity has been demonstrated to lie in the amino terminal half of the protein, which contains several discrete motifs including an imperfect glutamine-alanine (QA) repeat. In the present study, we showed that deletion of this domain completely abrogated the ability of TCERG1 to inhibit the growth arrest activity of C/EBPalpha. Moreover, the QA repeat deletion mutant of TCERG1 lost the ability to be relocalized from nuclear speckles to pericentromeric regions, and caused an increase in the average size of individual speckles. We also showed that deletion of the QA repeat abrogated the complex formation between TCERG1 and C/EBPalpha. Examination of mutants with varying numbers of QA repeats indicated that a minimal number of repeats are required for inhibitory activity as well as relocalization ability. These data contribute to our overall understanding of how TCERG1 can have gene-specific effects in addition to its more general roles in coordinating transcription elongation and splicing. PMID- 26264133 TI - Direct PCR Improves the Recovery of DNA from Various Substrates. AB - This study reports on the comparison of a standard extraction process with the direct PCR approach of processing low-level DNA swabs typical in forensic investigations. Varying concentrations of control DNA were deposited onto three commonly encountered substrates, brass, plastic, and glass, left to dry, and swabbed using premoistened DNA-free nylon FLOQswabs(TM) . Swabs (n = 90) were either processed using the DNA IQ(TM) kit or, for direct PCR, swab fibers (~2 mm(2) ) were added directly to the PCR with no prior extraction. A significant increase in the height of the alleles (p < 0.005) was observed when using the direct PCR approach over the extraction methodology when controlling for surface type and mass of DNA deposited. The findings indicate the potential use of direct PCR for increasing the PCR product obtained from low-template DNA samples in addition to minimizing contamination and saving resources. PMID- 26264134 TI - Development and validation of a novel patient-reported treatment satisfaction measure for hyperfunctional facial lines: facial line satisfaction questionnaire. AB - BACKGROUND: Facial lines or wrinkles are among the most visible signs of aging, and minimally invasive cosmetic procedures are becoming increasingly popular. AIMS: The aim of this study was to develop and validate the Facial Line Satisfaction Questionnaire (FLSQ) for use in adults with upper facial lines (UFL). METHODS: A literature review, concept elicitation interviews (n = 33), and cognitive debriefing interviews (n = 23) of adults with UFL were conducted to develop the FLSQ. The FLSQ comprises Baseline and Follow-up versions and was field-tested with 150 subjects in a US observational study designed to assess its psychometric performance. Analyses included acceptability (item and scale distribution [i.e. missingness, floor, and ceiling effects]), reliability, and validity (including concurrent validity). RESULTS: In total, 69 concepts were elicited during patient interviews. Following cognitive debriefing interviews, the FLSQ-Baseline version included 11 items and the Follow-up version included 13 items. Response rates for the FLSQ were 100% and 73% at baseline and follow-up, respectively; no items had excessive missing data. Questionnaire scale scores were normally distributed. Most domain scores demonstrated good internal consistency reliability (Cronbach's alpha >= 0.70). Most items within their respective domains exhibited good convergent (item-scale correlations > 0.40) and discriminant (items had higher correlation with their hypothesized scales than other scales) validity. Concurrent validity correlation coefficients of the FLSQ domain scores with the associated concurrent measures were acceptable (range: r = 0.40-0.70). Six FLSQ items demonstrated reliability and validity as stand-alone items outside their domains. CONCLUSIONS: The FLSQ is a valid questionnaire for assessing treatment expectations, satisfaction, impact, and preference in adults with UFL. PMID- 26264135 TI - Characterization of self-generated variants in Pseudoalteromonas lipolytica biofilm with increased antifouling activities. AB - Pseudoalteromonas is widespread in various marine environments, and most strains can affect invertebrate larval settlement and metamorphosis by forming biofilms. However, the impact and the molecular basis of population diversification occurring in Pseudoalteromonas biofilms are poorly understood. Here, we show that morphological diversification is prevalent in Pseudoalteromonas species during biofilm formation. Two types of genetic variants, wrinkled (frequency of 12+/-5%) and translucent (frequency of 5+/-3%), were found in Pseudoalteromonas lipolytica biofilms. The inducing activities of biofilms formed by the two variants on larval settlement and metamorphosis of the mussel Mytilus coruscus were significantly decreased, suggesting strong antifouling activities. Using whole genome re-sequencing combined with genetic manipulation, two genes were identified to be responsible for the morphology alternations. A nonsense mutation in AT00_08765 led to a wrinkled morphology due to the overproduction of cellulose, whereas a point mutation in AT00_17125 led to a translucent morphology via a reduction in capsular polysaccharide production. Taken together, the results suggest that the microbial behavior on larval settlement and metamorphosis in marine environment could be affected by the self-generated variants generated during the formation of marine biofilms, thereby rendering potential application in biocontrol of marine biofouling. PMID- 26264137 TI - Selective elimination of bacterial faecal indicators in the Schmutzdecke of slow sand filtration columns. AB - Slow sand filtration (SSF) is an effective low-tech water treatment method for pathogen and particle removal. Yet despite its application for centuries, it has been uncertain to which extent pathogenic microbes are removed by mechanical filtration or due to ecological interactions such as grazing and competition for nutrients. In this study, we quantified the removal of bacterial faecal indicators, Escherichia coli and Enterococcus faecalis, from secondary effluent of a wastewater treatment plant and analysed the microbial community composition in compartments of laboratory model SSF columns. The columns were packed with different sand grain sizes and eliminated 1.6-2.3 log units of faecal indicators, which translated into effluents of bathing water quality according to the EU directive (<500 colony forming units of E. coli per 100 ml) for columns with small grain size. Most of that removal occurred in the upper filter area, the Schmutzdecke. Within that same zone, total bacterial numbers increased however, thus suggesting a specific elimination of the faecal indicators. The analysis of the microbial communities also revealed that some taxa were removed more from the wastewater than others. These results accentuate the contribution of biological mechanisms to water purification in SSF. PMID- 26264136 TI - A novel aldose-aldose oxidoreductase for co-production of D-xylonate and xylitol from D-xylose with Saccharomyces cerevisiae. AB - An open reading frame CC1225 from the Caulobacter crescentus CB15 genome sequence belongs to the Gfo/Idh/MocA protein family and has 47 % amino acid sequence identity with the glucose-fructose oxidoreductase from Zymomonas mobilis (Zm GFOR). We expressed the ORF CC1225 in the yeast Saccharomyces cerevisiae and used a yeast strain expressing the gene coding for Zm GFOR as a reference. Cell extracts of strains overexpressing CC1225 (renamed as Cc aaor) showed some Zm GFOR type of activity, producing D-gluconate and D-sorbitol when a mixture of D glucose and D-fructose was used as substrate. However, the activity in Cc aaor expressing strain was >100-fold lower compared to strains expressing Zm gfor. Interestingly, C. crescentus AAOR was clearly more efficient than the Zm GFOR in converting in vitro a single sugar substrate D-xylose (10 mM) to xylitol without an added cofactor, whereas this type of activity was very low with Zm GFOR. Furthermore, when cultured in the presence of D-xylose, the S. cerevisiae strain expressing Cc aaor produced nearly equal concentrations of D-xylonate and xylitol (12.5 g D-xylonate l(-1) and 11.5 g D-xylitol l(-1) from 26 g D-xylose l(-1)), whereas the control strain and strain expressing Zm gfor produced only D-xylitol (5 g l(-1)). Deletion of the gene encoding the major aldose reductase, Gre3p, did not affect xylitol production in the strain expressing Cc aaor, but decreased xylitol production in the strain expressing Zm gfor. In addition, expression of Cc aaor together with the D-xylonolactone lactonase encoding the gene xylC from C. crescentus slightly increased the final concentration and initial volumetric production rate of both D-xylonate and D-xylitol. These results suggest that C. crescentus AAOR is a novel type of oxidoreductase able to convert the single aldose substrate D-xylose to both its oxidized and reduced product. PMID- 26264138 TI - Overexpression of yeast thioredoxin TRX2 reduces p53-mediated cell death in yeast. AB - We have previously shown that overexpression of the human tumor suppressor protein P53 causes cell death of the yeast Saccharomyces cerevisiae. P53 overproduction led to transcriptional downregulation of some yeast genes, such as the TRX1/2 thioredoxin system, which plays a key role in cell protection against various oxidative stresses induced by reactive oxygen species (ROS). In the present work, the impact of TRX2 overexpression on apoptosis mediated by p53 overexpression in yeast is investigated. In yeast cells expressing P53 under an inducible promoter together with TRX2 under a strong constitutive promoter, we showed that Tr2p overproduction reduced the apoptotic effect exerted by P53 and increased the viability of the P53-overproducing cells. Furthermore, measurements of ROS amounts by flow cytometry and fluorescence microscopy indicated that the TRX2 protein acted probably through its increased detoxifying activity on the P53 generated ROS. The steady-state level and activity of P53 were not affected by TRX2 overexpression, as shown by western blotting and functional analysis of separated alleles in yeast (FASAY), respectively. The growth inhibitory effect of P53 was partially reversed by the antioxidant N-acetylcysteine. Our data strengthen the idea that overexpression of a single gene (trx2) decreases the p53 mediated cell death by decreasing ROS accumulation. PMID- 26264139 TI - Two-step nitrification in a pure moving bed biofilm reactor-membrane bioreactor for wastewater treatment: nitrifying and denitrifying microbial populations and kinetic modeling. AB - The moving bed biofilm reactor-membrane bioreactor (MBBR-MBR) is a novel solution to conventional activated sludge processes and membrane bioreactors. In this study, a pure MBBR-MBR was studied. The pure MBBR-MBR mainly had attached biomass. The bioreactor operated with a hydraulic retention time (HRT) of 9.5 h. The kinetic parameters for heterotrophic and autotrophic biomasses, mainly nitrite-oxidizing bacteria (NOB), were evaluated. The analysis of the bacterial community structure of the ammonium-oxidizing bacteria (AOB), NOB, and denitrifying bacteria (DeNB) from the pure MBBR-MBR was carried out by means of pyrosequencing to detect and quantify the contribution of the nitrifying and denitrifying bacteria in the total bacterial community. The relative abundance of AOB, NOB, and DeNB were 5, 1, and 3%, respectively, in the mixed liquor suspended solids (MLSS), and these percentages were 18, 5, and 2%, respectively, in the biofilm density (BD) attached to carriers. The pure MBBR-MBR had a high efficiency of total nitrogen (TN) removal of 71.81+/-16.04%, which could reside in the different bacterial assemblages in the fixed biofilm on the carriers. In this regard, the kinetic parameters for autotrophic biomass had values of YA=2.3465 mg O2 mg N(-1), MUm, A=0.7169 h(-1), and KNH=2.0748 mg NL(-1). PMID- 26264140 TI - A Noble-Metal-Free Nickel(II) Polypyridyl Catalyst for Visible-Light-Driven Hydrogen Production from Water. AB - The complex [Ni(bpy)3](2+) (bpy=2,2'-bipyridine) is an active catalyst for visible-light-driven H2 production from water when employed with [Ir(dfppy)2 (Hdcbpy)] [dfppy=2-(3,4-difluorophenyl)pyridine, Hdcbpy=4-carboxy-2,2'-bipyridine 4'-carboxylate] as the photosensitizer and triethanolamine as the sacrificial electron donor. The highest turnover number of 520 with respect to the nickel(II) catalyst is obtained in a 8:2 acetonitrile/water solution at pH 9. The H2 evolution system is more stable after the addition of an extra free bpy ligand, owing to faster catalyst regeneration. The photocatalytic results demonstrate that the nickel(II) polypyridyl catalyst can act as a more effective catalyst than the commonly utilized [Co(bpy)3 ](2+). This study may offer a new paradigm for constructing simple and noble-metal-free catalysts for photocatalytic hydrogen production. PMID- 26264142 TI - Effect of the synthetic cannabinoid HU-210 on quorum sensing and on the production of quorum sensing-mediated virulence factors by Vibrio harveyi. AB - BACKGROUND: Bacterial populations communicate through the cell density-dependent mechanism of quorum sensing (QS). Vibrio harveyi, one of the best studied model organisms for QS, was used to explore effects of the synthetic cannabinoid HU-210 on QS and different QS-regulated physiological processes in bacteria. RESULTS: Analysis of QS-regulated bioluminescence in wild-type and mutant strains of V. harveyi revealed that HU-210 affects the autoinducer-2 (AI-2) pathway, one of three known QS cascades of V. harveyi. Furthermore, QS-mediated biofilm formation and swimming motility in the mutant strain BB152 (AI-1(-), AI-2(+)) were significantly reduced in the presence of HU-210. HU-210 inhibited QS-mediated virulence factor production without any inhibitory effect on bacterial growth. It also alters the expression of several genes, which are regulated by QS, specifically downregulating the genes of the AI-2 QS cascade. CONCLUSION: First evidence is being provided for interference of bacterial signal-transduction systems by a synthetic cannabinoid. The effect of HU-210 was specific to the AI-2 cascade in V. harveyi. AI-2 is known as a "universal autoinducer" and interference with its activity opens a broad spectrum of applications for synthetic cannabinoids in future research as a potential anti-QS agent. PMID- 26264143 TI - Impact of nocturnal hemodialysis on peripheral uremic neuropathy. AB - BACKGROUND: Uremic neuropathy is a common complication in patients with end stage kidney disease. Its pathogenesis has been attributed to accumulation of uremic toxins. Kidney transplantation has been the best therapeutic option. CASE PRESENTATION: We describe a case of severe uremic peripheral neuropathy, which improved after conversion from a conventional renal replacement therapy to nocturnal hemodialysis. CONCLUSION: Enhanced uremic control by intensive hemodialysis may contribute at least in part to clinical and neurophysiological improvements of uremic neuropathy. PMID- 26264144 TI - Genealogy of breastfeeding. AB - Decline and resurgence of breastfeeding (BF) characterized last century. Several factors influencing BF outcome were identified. Despite the huge literature on BF, no data on its matrilineal transmission are available. BF practice was prospectively followed in 2546 Italian mothers. Lactation and BF outcome were related, besides to known factors interfering with BF, to the occurrence of previous maternal and paternal BF. Recalls of grandmaternal and grand grandmaternal BF behaviours allowed the construction of familiar pedigrees of BF across three generations. Having been breastfed was the strongest factor addressing successful BF establishment (odds ratio (OR) 9.33; 95% confidence interval (CI) 7.40-11.84; p < 0.0001) and BF duration (at 6 months: OR 3.79; 95% CI 3.11-4.64; p < 0.0001). The hazard ratio for breastfed vs non-breastfed mothers was 0.46 (95% CI 0.41-0.50; log-rank p < 0.0001). The rate of BF failures was fivefold higher in non-breastfed mothers, mostly occurring during lactogenesis when the let-down reflex becomes essential. CONCLUSION: At any generation, mothers are likely to have daughters repeating their BF experience. Differently from the intergenerational effects of environmental factors responsible for the BF secular trend, this trait is transgenerationally transmitted and reversible, with temporal and clinical features of lactation failure. Accordingly, we speculate that epigenetic mechanisms might alter offspring's oxytocinergic receptor signalling. WHAT IS KNOWN: Several cultural and socio-demographic factors are known to influence breastfeeding outcome. The generational effects of breastfeeding itself have not been investigated so far. WHAT IS NEW: Maternal breastfeeding is the most important factor addressing daughters' breastfeeding outcome. This behavior is transmitted transgenerationally, with features suggesting epigenetic mechanisms. PMID- 26264145 TI - Prevalence of common fusion transcripts in acute lymphoblastic leukemia: A report of 304 cases. AB - AIM: Information about fusion transcripts in acute lymphoblastic leukemia (ALL) is used to risk-stratify patients, decide on the treatment and to detect minimal residual disease. This study was conducted to determine the frequency of common fusion transcripts BCR-ABL, TEL-AML1, MLL-AF4 and E2A-PBX1 for B-ALL and SIL-TAL1 for T-ALL as seen at a tertiary care center in India. METHODS: Up to 304 new cases of ALL (271 B-ALL and 33 T-ALL) diagnosed on morphology, cytochemistry and immunophenotyping were studied. All were screened for the common fusion transcripts by RT-PCR. RESULTS: Both our B- (218/271; 80.4%) and T-ALL (26/33; 78.8%) patients were largely children. In the B-ALL children, BCR-ABL was detected in 26/218 (11.9%), E2A-PBX1 in 13/218 (5.9%), TEL-AML1 in 16/218 (7.3%) and MLL-AF4 in 3/218 (1.4%) patients. Adult B-ALL cases had BCR-ABL in 15/53 (28.3%) and E2A-PBX in 2/53 (3.8%); however, no other fusion transcript was detected. SIL-TAL1 was found in four of 26 pediatric (15%) and zero of 7 adult T ALL cases. CONCLUSION: The higher incidence of BCR-ABL and lower incidence of TEL AML1 in our ALL patients, both in children and adults as compared with the West, suggests that patients in India may be biologically different. This difference may explain at least in part the higher relapse rate and poorer outcome in our B ALL cases. PMID- 26264146 TI - The prognostic value of serum C-reactive protein-bound serum amyloid A in early stage lung cancer. AB - BACKGROUND: Elevated levels of serum C-reactive protein (CRP) have been reported to have prognostic significance in lung cancer patients. This study aimed to further identify CRP-bound components as prognostic markers for lung cancer and validate their prognostic value. METHODS: CRP-bound components obtained from the serum samples from lung cancer patients or healthy controls were analyzed by differential proteomics analysis. CRP-bound serum amyloid A (CRP-SAA) was evaluated by co-immunoprecipitation (IP). Serum samples from two independent cohorts with lung cancer (retrospective cohort, 242 patients; prospective cohort, 222 patients) and healthy controls (159 subjects) were used to evaluate the prognostic value of CRP-SAA by enzyme-linked immunosorbent assay. RESULTS: CRP SAA was identified specifically in serum samples from lung cancer patients by proteomic analysis. CRP binding to SAA was confirmed by co-IP in serum samples from lung cancer patients and cell culture media. The level of CRP-SAA was significantly higher in patients than in healthy controls (0.37 +/- 0.58 vs. 0.03 +/- 0.04, P < 0.001). Elevated CRP-SAA levels were significantly associated with severe clinical features of lung cancer. The elevation of CRP-SAA was associated with lower survival rates for both the retrospective (hazard ration [HR] = 2.181, 95% confidence interval [CI] = 1.641-2.897, P < 0.001) and the prospective cohorts (HR = 2.744, 95% CI = 1.810-4.161, P < 0.001). Multivariate Cox analysis showed that CRP-SAA was an independent prognostic marker for lung cancer. Remarkably, in stages I-II patients, only CRP-SAA, not total SAA or CRP, showed significant association with overall survival in two cohorts. Moreover, univariate and multivariate Cox analyses also showed that only CRP-SAA could be used as an independent prognostic marker for early-stage lung cancer patients. CONCLUSION: CRP-SAA could be a better prognostic marker for lung cancer than total SAA or CRP, especially in early-stage patients. PMID- 26264147 TI - Inhibitory effect of Samul-tang on retinal neovascularization in oxygen-induced retinopathy. AB - BACKGROUND: Retinal neovascularization is a common cause of vision loss in proliferative diabetic retinopathy, retinopathy of prematurity and age-related macular degeneration. Samul-tang (SMT) is a widely used traditional herbal medicine in East Asia and is also known as Shimotsu-to in Japanese and Si-Wu decoction in Chinese. This study was designed to evaluate the inhibitory effect of SMT on retinal pathogenic angiogenesis in a mouse model of oxygen-induced retinopathy (OIR). METHOD: The mice were exposed to a 75% concentration of oxygen for five days, starting on postnatal day 7 (P7-P12). The mice were then exposed to room air and were intraperitoneally injected with SMT (10 mg/kg or 50 mg/kg) once per day for five days (P12-P16). On P17, we measured retinal neovascularization and evaluated both the expression of angiogenesis-related proteins and changes in the gene expression level in the mRNA. RESULTS: SMT reduced the area of the central retina and reduced retinal neovascularization in OIR mice. The protein array revealed that SMT reduced the level of SDF-1 protein expression. Quantitative real-time PCR revealed that the HIF-1alpha, SDF-1, CXCR4 and VEGF mRNA levels in the retinas of OIR mice were elevated compared with those of normal control mice. However, SMT decreased the levels of HIF-1alpha, SDF-1, CXCR4 and VEGF mRNA in OIR mice. CONCLUSION: We are the first to elucidate that SMT inhibits the retinal pathogenic angiogenesis induced by ischemic retinopathy in OIR mice. SMT significantly inhibited retinal neovascularization by downregulating HIF-1alpha, SDF-1, CXCR4 and VEGF. Based on the results of our study, SMT could be a useful herbal medicine for treating ischemic retinopathy. PMID- 26264148 TI - Stress-triggered redox signalling: what's in pROSpect? AB - Reactive oxygen species (ROS) have a profound influence on almost every aspect of plant biology. Here, we emphasize the fundamental, intimate relationships between light-driven reductant formation, ROS, and oxidative stress, together with compartment-specific differences in redox buffering and the perspectives for their analysis. Calculations of approximate H2 O2 concentrations in the peroxisomes are provided, and based on the likely values in other locations such as chloroplasts, we conclude that much of the H2 O2 detected in conventional in vitro assays is likely to be extracellular. Within the context of scant information on ROS perception mechanisms, we consider current knowledge, including possible parallels with emerging information on oxygen sensing. Although ROS can sometimes be signals for cell death, we consider that an equally important role is to transmit information from metabolism to allow appropriate cellular responses to developmental and environmental changes. Our discussion speculates on novel sensing mechanisms by which this could happen and how ROS could be counted by the cell, possibly as a means of monitoring metabolic flux. Throughout, we place emphasis on the positive effects of ROS, predicting that in the coming decades they will increasingly be defined as hallmarks of viability within a changing and challenging environment. PMID- 26264149 TI - Impact of body mass index on posttransplant outcomes reexamined. PMID- 26264150 TI - Vemurafenib-induced progression of breast cancer: a case report and review of the literature. AB - Vemurafenib, a specific inhibitor of mutated BRAF kinase, may activate wild-type BRAF and therefore induce squamous cell skin carcinomas in patients treated for melanoma. All vemurafenib clinical trials excluded patients with multiple primary malignant tumors; therefore, the action of this drug on concurrent BRAF wild-type malignancies remains insufficiently studied. We observed a patient, who was administered vemurafenib for BRAF mutation-containing melanoma, but experienced immediate relapse of previously controlled breast cancer disease. Interestingly, breast cancer lesions underwent regression soon after vemurafenib discontinuation. Therefore, caution must be taken while considering vemurafenib treatment for patients with multiple tumors. PMID- 26264151 TI - [Age and infections: From time immemorial two of the most closely linked topics]. PMID- 26264152 TI - Transepidermal elimination of mucin is a very common but not yet reported phenomenon in digital myxoid cysts: a study of 35 cases. AB - We present a series of 35 cases of digital myxoid cyst in which we specifically looked for transepidermal migration of mucin. We found it in 57.14% of the cases (20/35). In these cases, there were collections of mucin in an intraepidermal bulla as well as multiple intercellular droplets of mucin in many cases. All cases of perforating mucinosis described so far in the literature have presented clinically as papular eruptions. We therefore conclude that (1) perforating mucinoses do not exclusively present as multiple papules but also occur as single lesions; (2) transepidermal elimination of mucin is a very common but not yet reported phenomenon in digital myxoid cysts; (3) the morphological findings suggest real transepidermal migration of the mucin instead of exposure of the mucin to the surface via ulceration. PMID- 26264153 TI - Application of F+RNA Coliphages as Source Tracking Enteric Viruses on Parsley and Leek Using RT-PCR. AB - The objective of this study was to identify sources of fecal contamination in leek and parsley, by using four different F(+)RNA coliphage genogroups (IV, I indicate animal fecal contamination and II, III indicate human fecal contamination). Three different concentrations (10(2), 10(4), 10(6) pfu/ml) of MS2 coliphage were inoculated on the surface of parsley and leek samples for detection of phage recovery efficiency among two methods of elution concentration (PEG-precipitation and Ultracentrifugation) by performing double agar layer (DAL) assay in three replications. Highest recovery of MS2 was observed in PEG method and in 10(6) inoculation concentration. Accordingly, the PEG method was used for washing and isolation of potentially contaminated phages of 30 collected samples (15 samples from the market and 15 samples from the farm). The final solutions of PEG method were tested for the enumeration of plaques by DAL assay. Total RNA was then extracted from recovered phages, and RT-PCR was performed by using four primer sets I, II, III, and IV. Incidence of F(+)RNA coliphages was observed in 12/15 (80 %) and 10/15 (66/6 %) of samples were obtained from farm and market, respectively, using both DAL and RT-PCR test methods. Different genotypes (I, II, and IV) of F(+)RNA coliphages were found in farm samples, while only genotype I was detected in market samples by using the primer sets. Due to the higher frequency of genotype I and IV, the absence of genotype III, and also the low frequency of genotype II, it is concluded that the contamination of vegetable (parsley and leek) in Neyshabour, Iran is most likely originated from animal sources. PMID- 26264154 TI - Assessing mediators between discrimination, health behaviours and physical health outcomes: a representative cross-sectional study. AB - PURPOSE: Discrimination is a social determinant of health; however, the pathways linking discrimination to ill-health are under-researched. This study investigated the mediators through which discrimination affects health behaviours and physical health outcomes, as well as assessed whether sex moderated these mechanisms. METHODS: Data from a representative survey (n = 1023) of undergraduate students enrolled in a Brazilian university in 2012 were used. Structural equation models were applied to assess the following mediation mechanisms--(1) discrimination influences self-rated health and body mass index via anxiety/depression; (2) discrimination affects behaviours (alcohol consumption, problem drinking, smoking, fruit/vegetable consumption, and physical activity) through discomfort associated with discriminatory experiences. The potential of sex to act as an effect-modifying variable was also explored in each of the postulated pathways. RESULTS: The effect of discrimination on self-rated poor health was totally (100.0%) mediated by anxiety/depression, while body mass index was not correlated with discrimination. Self-reported discrimination was associated with some behaviours via discomfort. Particularly, discomfort partially mediated the positive association between discrimination, leisure time physical activity (43.3%), and fruit/vegetable consumption (52.2%). Sex modified the association between discrimination, discomfort and physical activity in that such mechanism (more discrimination -> more discomfort -> more physical activity) was statistically significant in the entire sample and among females, but not among males. CONCLUSIONS: This is one of the first studies to demonstrate that discrimination is associated with physical health outcomes and behaviours via distinct pathways. Future investigations should further explicate the mediational pathways between discrimination and key health outcomes. PMID- 26264155 TI - External morphological anomalies in ixodid ticks from Thrace, Turkey. AB - Of 18,667 ticks examined, 33 specimens from species identified as Haemaphysalis parva, Hyalomma marginatum, Hy. scupense, Rhipicephalus bursa and Rh. turanicus were found to have external morphological anomalies. Anomalous Ha. parva, Hy. scupence and Rh. turanicus were reported in this study for the first time. General anomalies manifested as asymmetry and deformations of the idiosoma, whereas local anomalies occurred in legs, exoskeleton, spiracular, adanal, subanal and accessory plates, mouthparts and capitulum. With this study describing a gynandromorphic Hy. marginatum, the number of gynandromorphic tick cases has been raised to two in Turkey. PMID- 26264156 TI - Taxonomic distribution of defensive alkaloids in Nearctic oribatid mites (Acari, Oribatida). AB - The opisthonotal (oil) glands of oribatid mites are the source of a wide diversity of taxon-specific defensive chemicals, and are likely the location for the more than 90 alkaloids recently identified in oribatids. Although originally recognized in temperate oribatid species, alkaloids have also been detected in related lineages of tropical oribatids. Many of these alkaloids are also present in a worldwide radiation of poison frogs, which are known to sequester these defensive chemicals from dietary arthropods, including oribatid mites. To date, most alkaloid records involve members of the superfamily Oripodoidea (Brachypylina), although few species have been examined and sampling of other taxonomic groups has been highly limited. Herein, we examined adults of more than 60 species of Nearctic oribatid mites, representing 46 genera and 33 families, for the presence of alkaloids. GC-MS analyses of whole body extracts led to the detection of 15 alkaloids, but collectively they occur only in members of the genera Scheloribates (Scheloribatidae) and Protokalumma (Parakalummidae). Most of these alkaloids have also been detected previously in the skin of poison frogs. All examined members of the oripodoid families Haplozetidae and Oribatulidae were alkaloid-free, and no mites outside the Oripodoidea contained alkaloids. Including previous studies, all sampled species of the cosmopolitan oripodoid families Scheloribatidae and Parakalummidae, and the related, mostly tropical families Mochlozetidae and Drymobatidae contain alkaloids. Our findings are consistent with a generalization that alkaloid presence is widespread, but not universal in Oripodoidea. Alkaloid presence in tropical, but not temperate members of some non-oripodoid taxa (in particular Galumnidae) deserves further study. PMID- 26264157 TI - Re: Lars Budaus, Sami-Ramzi Leyh-Bannurah, Georg Salomon, et al. Initial Experience of (68)Ga-PSMA PET/CT Imaging in High-risk Prostate Cancer Patients Prior to Radical Prostatectomy. Eur Urol 2016;69:393-6. PMID- 26264158 TI - Magnetic Resonance Imaging Before Prostate Biopsy: Time to Talk. AB - MRI directed prostate biopsy will change the cancer risk profiles of diagnosed patients, towards those requiring radical treatments. Increased costs can be balanced by improvements in the efficiency of the patient pathway. Effective communication of imaging findings and improved urological understanding of imaging limitations will improve the quality of care for prostate cancer patients. PMID- 26264159 TI - Single-agent Taxane Versus Taxane-containing Combination Chemotherapy as Salvage Therapy for Advanced Urothelial Carcinoma. AB - BACKGROUND: Single-agent taxanes are commonly used as salvage systemic therapy for patients with advanced urothelial carcinoma (UC). OBJECTIVE: To study the impact of combination chemotherapy delivering a taxane plus other chemotherapeutic agents compared with single-agent taxane as salvage therapy. DESIGN, SETTING, AND PARTICIPANTS: Individual patient-level data from phase 2 trials of salvage systemic therapy were used. INTERVENTIONS: Trials evaluating either single agents (paclitaxel or docetaxel) or combination chemotherapy (taxane plus one other chemotherapeutic agent or more) following prior platinum based therapy were used. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Information regarding the known major baseline prognostic factors was required: time from prior chemotherapy, hemoglobin, performance status, albumin, and liver metastasis status. Cox proportional hazards regression was used to evaluate the association of prognostic factors and combination versus single-agent chemotherapy with overall survival (OS). RESULTS AND LIMITATIONS: Data were available from eight trials including 370 patients; two trials (n=109) evaluated single-agent chemotherapy with docetaxel (n=72) and cremophor-free paclitaxel (n=37), and six trials (n=261) evaluated combination chemotherapy with gemcitabine-paclitaxel (two trials, with n=99 and n=24), paclitaxel cyclophosphamide (n=32), paclitaxel-ifosfamide-nedaplatin (n=45), docetaxel ifosfamide-cisplatin (n=26), and paclitaxel-epirubicin (n=35). On multivariable analysis after adjustment for baseline prognostic factors, combination chemotherapy was independently and significantly associated with improved OS (hazard ratio: 0.60; 95% confidence interval, 0.45-0.82; p=0.001). The retrospective design of this analysis and the trial-eligible population were inherent limitations. CONCLUSIONS: Patients enrolled in trials of combination chemotherapy exhibited improved OS compared with patients enrolled in trials of single-agent chemotherapy as salvage therapy for advanced UC. Prospective randomized trials are required to validate a potential role for rational and tolerable combination chemotherapeutic regimens for the salvage therapy of advanced UC. PATIENT SUMMARY: This retrospective study suggests that a combination of chemotherapy agents may extend survival compared with single-agent chemotherapy in selected patients with metastatic urothelial cancer progressing after prior chemotherapy. PMID- 26264160 TI - Outcomes for Patients with Clinical Lymphadenopathy Treated with Radical Prostatectomy. AB - Clinical lymphadenopathy (cN+) from prostate cancer (PCa) identified on imaging remains a contraindication to radical prostatectomy (RP) according to guidelines. We tested the hypothesis that there would be no difference in survival between patients with and without cN+ on preoperative imaging who underwent RP and pelvic lymph node dissection with detection of pelvic lymph node metastasis (LNM). A total of 302 patients with LNM were retrospectively reviewed (1988-2003) and stratified according to cN status on the basis of preoperative imaging. Univariable and multivariable Cox regression analyses were performed to evaluate cN+ as a predictor of survival. Of the 302 patients, 50 (17%) had cN+; the 252 (83%) patients with negative preoperative imaging comprised the cN0 group. During median follow-up of 17.4 yr, 161 deaths were recorded, 70 of which were from PCa. Among the entire LNM cohort, the number of positive lymph nodes (hazard ratio [HR] 1.10; p=0.02) and pathologic Gleason score 8-10 versus <=6 (HR 2.37; p=0.04) were significant predictors of cancer-specific mortality (CSM). cN+ was not a significant predictor of CSM (p=0.6). Selected patients with cN+ have similar clinical outcomes to those with normal preoperative imaging in the setting of LNM. PATIENT SUMMARY: Clinical lymph node metastases are not a factor in determining survival after radical prostatectomy and pelvic lymph node dissection in patients with prostate cancer. Thus, the presence of clinical lymph node metastases should not be considered as an absolute contraindication to treatment with curative intent. PMID- 26264161 TI - Fluoride release and recharging ability of new dental sealants. AB - AIM: This in vitro investigation was to evaluate the fluoride release and recharge abilities of three recently introduced dental fissure sealants (FS). METHODS: Three dental FS were assessed: Teethmate F-1 (Kuraray), Fissurit F (Voco), BeautiSealant (Shofu), and a conventional glass ionomer cement FX-II (Shofu) as a control. Eight cylindrical specimens (7 * 2 mm) of each material were made and immersed individually in 5 ml de-ionized water in plastic containers. Fluoride release of the tested materials was evaluated during the experimental period (28 days) utilising a fluoride ion-selective electrode. At the end of the test period, the specimens were soaked for 5 min in a fluoride solution (0.05 % NaF) and fluoride release was evaluated for the next 5 days. The data were statistically analysed using one-way ANOVA and Bonferroni post hoc test and the level of significance was preset at alpha = 0.05. RESULTS: The total fluoride release over the 28-day period for each material was: FX-II (408.6 +/- 45.66 MUg/cm(2)) > Teethmate F-1 (89.45 +/- 12.32 MUg/cm(2)) > Fissurit F (68.62 +/- 8.72 MUg/cm(2)) > BeautiSealant (33.32 +/- 4.91 MUg/cm(2)), (p < 0.05). After the re-fluoridation of the specimens with 0.05 % NaF solution the cumulative fluoride re-release during the 5-day period for each material was: FX-II (99.53 +/- 13.21 MUg/cm(2)) > Teethmate F-1 (9.76 +/- 1.62 MUg/cm(2)) > BeautiSealant (5.69 +/- 0.89 MUg/cm(2)) > Fissurit F (4.76 +/- 0.72 MUg/cm(2)), (p < 0.05). CONCLUSIONS: The three tested sealants exhibited different capabilities to release and uptake fluoride ions after re-fluoridation but significantly lower than the glass ionomer tested. PMID- 26264162 TI - Endocrine activity of persistent organic pollutants accumulated in human silicone implants--Dosing in vitro assays by partitioning from silicone. AB - Persistent organic pollutants (POPs) accumulated in human tissues may pose a risk for human health by interfering with the endocrine system. This study establishes a new link between actual human internal POP levels and the endocrine active dose in vitro, applying partitioning-controlled dosing from silicone to the H295R steroidogenesis assay: (1) Measured concentrations of POPs in silicone breast implants were taken from a recent study and silicone disks were loaded according to these measurements. (2) Silicone disks were transferred into H295R cell culture plates in order to control exposure of the adrenal cells by equilibrium partitioning. (3) Hormone production of the adrenal cells was measured as toxicity endpoint. 4-Nonylphenol was used for method development, and the new dosing method was compared to conventional solvent-dosing. The two dosing modes yielded similar dose-dependent hormonal responses of H295R cells. However, with the partitioning-controlled freely dissolved concentrations (Cfree) as dose metrics, dose-response curves were left-shifted by two orders of magnitude relative to spiked concentrations. Partitioning-controlled dosing of POPs resulted in up to 2-fold increases in progestagen and corticosteroid levels at Cfree of individual POPs in or below the femtomolar range. Silicone acted not only as source of the POPs but also as a sorption sink for lipophilic hormones, stimulating the cellular hormone production. Methodologically, the study showed that silicone can be used as reference partitioning phase to transfer in vivo exposure in humans (silicone implants) to in vitro assays (partition-controlled dosing). The main finding was that POPs at the levels at which they are found in humans can interfere with steroidogenesis in a human adrenocortical cell line. PMID- 26264163 TI - Telmisartan mediates anti-inflammatory and not cognitive function through PPAR gamma agonism via SARM and MyD88 signaling. AB - Telmisartan (TM), an angiotensin II receptor I (AT1) blocker, has been reported to have agonist property with respect to PPAR-gamma. Activation of PPAR-gamma receptor by TM attenuated the lipopolysaccharide (LPS) mediated TLR4 central downstream inflammatory responses. However, the missing link between PPAR-gamma and TLR4 signaling with TM stimulation has not been clarified. Hence, the present study has been designed to evaluate the molecular mechanism involving PPARgamma TLR4 signaling with TM stimulation in LPS induced inflammatory model. LPS was administered in rats through ICV and the rats were treated with either PPAR-gamma antagonist GW9662 (GW) or TM or both. After 14days of LPS administration, the rats were subjected to behavioral tests and their brains were isolated for blotting techniques. The protein study includes NF-kappaB, PPAR-gamma receptors, and their downstream proteins (MyD88 & SARM). The pro-inflammatory cytokines (TNF alpha, IL-1beta, IL-6) levels were measured by ELISA and cresyl violet staining in the hippocampus region to measure the neuroprotective activity. Results have shown that TM significantly increased the motor co-ordination, cognitive functions, and activated SARM and PPAR-gamma protein levels. Also, TM treatment decreased the NF-kappaB, MyD88 activation, and cytokines release in LPS rats. The co-administration of GW attenuated the TM responses in the parameters studied except cognitive functions. TM (10mg/kg) has significantly reduced the LPS mediated inflammatory responses. This resulted in effective regeneration of hippocampal neurons as observed by cresyl violet staining. It can be concluded that the activation of PPAR-gamma receptors may increase the SARM and decrease the MyD88 and NF-kappaB expression. This negative regulation of SARM dependent inflammation control could be a possible mechanism for TM anti-neuroinflammatory activity. This study of TM in neuro-inflammatory model may further confirm the dual activities of TM that controls hypertension and cognition through AT1 blockade and also attenuates neuro-inflammation via PPAR-gamma agonistic property. PMID- 26264165 TI - Adaptation and psychometric testing of the Practice Environment Scale for use with midwives. AB - BACKGROUND: The Practice Environment Scale (PES) has been used extensively to measure the quality of the practice environment of nurses working in a variety of work settings, and has been linked with quality of care, nurse wellbeing, job dissatisfaction and burnout. Although developed for nurses, many of the aspects addressed by the PES are also relevant to the midwifery profession, and may provide a tool to better understand midwives' decision to leave the profession. AIM: To adapt the PES for use with midwives and to assess its psychometric properties. METHODS: An online survey containing the adapted version of the PES was distributed to a sample of hospital-employed New Zealand midwives (n=600). Exploratory factor analysis was conducted to identify subscales which were compared for midwives who had, versus had not considered, leaving the midwifery profession. FINDINGS: Four subscales were identified, showing good internal consistency reliability (Quality of Management, Midwife-Doctor Relations, Resource Adequacy and Opportunities for Development). The lowest mean score was recorded for Resource Adequacy (M=2.38). All subscales of the adapted 20-item PES:Midwives were significant predictors of the decision to leave the profession (p<.001) with odds ratios above 2.0. The strongest predictor was Quality of Management (OR=2.6). CONCLUSION: The PES:Midwives was successfully adapted for use with midwives and provides a psychometrically sound tool for research to identify factors associated with the wellbeing, job satisfaction and risk of attrition amongst hospital employed midwives. The PES:Midwives also provides a means of comparing the practice environment across different models of care and employing organizations. PMID- 26264164 TI - A Comprehensive Analysis of Influence ERCC Polymorphisms Confer on the Development of Brain Tumors. AB - Within DNA repair genes, there lie a number of single nucleotide polymorphisms that may impair protein function and attenuate DNA repair capability, resulting in genomic instability and individual predisposition to malignancies. The purpose of this study was to assess the previously reported inconsistent association of polymorphisms in ERCC1 (rs11615, rs3212986), ERCC2 (rs13181, rs1799793, rs238406), and ERCC5 (rs17655) with the development of brain tumors. In the present work, we carried out a comprehensive meta-analysis of results from all published data (5 data sets for rs11615, 7 for rs3212986, 11 for rs13181, 5 for rs1799793, 3 for rs238406, and 4 for rs17655) to evaluate risk of brain tumors contributed by the polymorphisms being investigated. Either the analytic method described by Mantel and Haenszel or that proposed by DerSimonian and Laird was properly used to summarize the risk estimates (OR and 95% CI). Data analyses were done with Stata version 12.0. Meta-analyses were performed for all polymorphisms, and only rs3212986 in the ERCC1 gene showed a significant association with glioma incidence. In the homozygote comparison, we found 1.26-fold elevated risk of glioma in relation to presence of the AA genotype (OR = 1.26, 95% CI = 1.05-1.52, P OR = 0.013, P heterogeneity = 0.849, I(2) = 0.0%). We also noted that individuals with the rs3212986-AA as compared to those with rs3212986-CC/CA had a 28% higher risk to develop glioma (OR = 1.28, 95% CI = 1.06-1.53, P OR = 0.008, Pheterogeneity = 0.808, I(2) = 0.0%). No major effects were observed for Caucasians or Asians in subgroup analysis by ethnicity. ERCC1 rs3212986 is a common single nucleotide polymorphism and may contribute toward individual susceptibility for glioma. Further research in this filed is required to verify the association obtained based on a relatively small number. PMID- 26264166 TI - Reverse micelles prepared from amphiphilic polylactide-b-poly(ethylene glycol) block copolymers for controlled release of hydrophilic drugs. AB - This work aims to evaluate the potential of reverse micelles prepared from amphiphilic polylactide-b-poly(ethylene glycol) (PLA-b-PEG) block copolymers for controlled release of hydrophilic drugs. Different PLA-b-PEG diblock and triblock copolymers were synthesized by ring-opening polymerization of D- or L-lactide in the presence of a PEG macroinitiator. Reverse micelles were prepared by self assembly of copolymers in a solvent/co-solvent/water system. Toluene was used as solvent, and ethanol as co-solvent to solubilize appropriate amount of water. The resulting nano-sized reverse micelles were able to encapsulate heparin in the hydrophilic core. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) were used to determine the size and morphology of reverse micelles. The results show that reverse micelles are spherical in shape with sizes below 100 nm. Drug loaded reverse micelles were embedded in biocompatible membranes by mixing with 10% PLA solution in toluene with 1:3 volume ratio. In vitro release studies were realized in phosphate buffer saline (PBS) at 37 degrees C. Heparin was almost totally released within 24h. Triblock copolymer reverse micelles exhibited faster drug release than diblock ones probably due to the more compact micelle structure of the latter. Therefore, PLA-b-PEG reverse micelles could be promising for applications as carrier of hydrophilic drugs when embedded in biocompatible membranes. PMID- 26264167 TI - Low cancer suspicion following experience of a cancer 'warning sign'. AB - AIM: Lower socioeconomic status (SES) is associated with a higher risk of late stage cancer diagnosis. A number of explanations have been advanced for this, but one which has attracted recent attention is lower patient knowledge of cancer warning signs, leading to delay in help-seeking. However, although there is psychometric evidence of SES differences in knowledge of cancer symptoms, no studies have examined differences in 'cancer suspicion' among people who are actually experiencing a classic warning sign. METHODS: A 'health survey' was mailed to 9771 adults (?50years, no cancer diagnosis) with a symptom list including 10 cancer 'warning signs'. Respondents were asked if they had experienced any of the symptoms in the past 3months, and if so, were asked 'what do you think caused it?' Any mention of cancer was scored as 'cancer suspicion'. SES was indexed by education. RESULTS: Nearly half the respondents (1732/3756) had experienced a 'warning sign', but only 63/1732 (3.6%) mentioned cancer as a possible cause. Lower education was associated with lower likelihood of cancer suspicion: 2.6% of respondents with school-only education versus 7.3% with university education suspected cancer as a possible cause. In multivariable analysis, low education was the only demographic variable independently associated with lower cancer suspicion (odds ratio (OR)=0.34, confidence interval (CI): 0.20-0.59). CONCLUSION: Levels of cancer suspicion were low overall in this community sample, and even lower in people from less educated backgrounds. This may hinder early symptomatic presentation and contribute to inequalities in stage at diagnosis. PMID- 26264169 TI - Papaverine 7-O-demethylase, a novel 2-oxoglutarate/Fe(2+)-dependent dioxygenase from opium poppy. AB - Opium poppy (Papaver somniferum) produces several pharmacologically important benzylisoquinoline alkaloids including the vasodilator papaverine. Pacodine and palaudine are tri-O-methylated analogs of papaverine, which contains four O linked methyl groups. However, the biosynthetic origin of pacodine and palaudine has not been established. Three members of the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy display widespread O-dealkylation activity on several benzylisoquinoline alkaloids with diverse structural scaffolds, and two are responsible for the antepenultimate and ultimate steps in morphine biosynthesis. We report a novel 2ODD from opium poppy catalyzing the efficient substrate- and regio-specific 7-O-demethylation of papaverine yielding pacodine. The occurrence of papaverine 7-O-demethylase (P7ODM) expands the enzymatic scope of the 2ODD family in opium poppy and suggests an unexpected biosynthetic route to pacodine. PMID- 26264168 TI - Managing perianal Crohn's fistula in the anti-TNFalpha era. AB - Perianal fistulas in Crohn's disease are common and difficult to treat. Their aetiology is poorly understood. Assessment is clinical, endoscopic and radiological, and management is undertaken by a multidisciplinary team of gastroenterologists, surgeons and radiologists. Surgical drainage of the fistula tract system with the placement of loose setons precedes combined therapy with immunosuppressant and anti-TNFalpha agents in most patients. Proctitis should be rigorously eliminated where possible. Definitive surgical repair is sometimes possible and diversion or proctectomy are occasionally required. Combined medical and surgical management represents a promising avenue for the future. PMID- 26264170 TI - Finite time stabilization of delayed neural networks. AB - In this paper, the problem of finite time stabilization for a class of delayed neural networks (DNNs) is investigated. The general conditions on the feedback control law are provided to ensure the finite time stabilization of DNNs. Then some specific conditions are derived by designing two different controllers which include the delay-dependent and delay-independent ones. In addition, the upper bound of the settling time for stabilization is estimated. Under fixed control strength, discussions of the extremum of settling time functional are made and a switched controller is designed to optimize the settling time. Finally, numerical simulations are carried out to demonstrate the effectiveness of the obtained results. PMID- 26264171 TI - Matrix measure method for global exponential stability of complex-valued recurrent neural networks with time-varying delays. AB - In this paper, based on the matrix measure method and the Halanay inequality, global exponential stability problem is investigated for the complex-valued recurrent neural networks with time-varying delays. Without constructing any Lyapunov functions, several sufficient criteria are obtained to ascertain the global exponential stability of the addressed complex-valued neural networks under different activation functions. Here, the activation functions are no longer assumed to be derivative which is always demanded in relating references. In addition, the obtained results are easy to be verified and implemented in practice. Finally, two examples are given to illustrate the effectiveness of the obtained results. PMID- 26264172 TI - Maximum margin semi-supervised learning with irrelevant data. AB - Semi-supervised learning (SSL) is a typical learning paradigms training a model from both labeled and unlabeled data. The traditional SSL models usually assume unlabeled data are relevant to the labeled data, i.e., following the same distributions of the targeted labeled data. In this paper, we address a different, yet formidable scenario in semi-supervised classification, where the unlabeled data may contain irrelevant data to the labeled data. To tackle this problem, we develop a maximum margin model, named tri-class support vector machine (3C-SVM), to utilize the available training data, while seeking a hyperplane for separating the targeted data well. Our 3C-SVM exhibits several characteristics and advantages. First, it does not need any prior knowledge and explicit assumption on the data relatedness. On the contrary, it can relieve the effect of irrelevant unlabeled data based on the logistic principle and maximum entropy principle. That is, 3C-SVM approaches an ideal classifier. This classifier relies heavily on labeled data and is confident on the relevant data lying far away from the decision hyperplane, while maximally ignoring the irrelevant data, which are hardly distinguished. Second, theoretical analysis is provided to prove that in what condition, the irrelevant data can help to seek the hyperplane. Third, 3C-SVM is a generalized model that unifies several popular maximum margin models, including standard SVMs, Semi-supervised SVMs (S(3)VMs), and SVMs learned from the universum (U-SVMs) as its special cases. More importantly, we deploy a concave-convex produce to solve the proposed 3C-SVM, transforming the original mixed integer programming, to a semi-definite programming relaxation, and finally to a sequence of quadratic programming subproblems, which yields the same worst case time complexity as that of S(3)VMs. Finally, we demonstrate the effectiveness and efficiency of our proposed 3C-SVM through systematical experimental comparisons. PMID- 26264173 TI - Effect of Resistance Exercises on the Indicators of Muscle Reserves and Handgrip Strength in Adult Patients on Hemodialysis. AB - OBJECTIVE: Although resistance exercise has been associated with improvement in the muscle reserves, muscle strength and quality of life in end-stage renal disease patients, the objective of this paper is to evaluate the effect of resistance exercise performed during hemodialysis sessions on the anthropometric indicators of muscle reserve and handgrip strength in sedentary malnourished patients with end-stage renal disease. METHODS: Patients were randomized to perform resistance exercise during hemodialysis sessions with ankle weights and resistance bands. The exercises were performed twice a week over the course of 12 weeks. The control group underwent a hemodialysis session alone. The outcomes measures were the following anthropometric measurements: arm muscle circumference and arm muscle area. Dynamometry was used to measure the handgrip strength. RESULTS: Sixty-one sedentary patients with a median age of 29 years (interquartile range [IQR] 21-39 years), and 83% presenting with some grade of malnutrition were equally randomized to either the intervention or control group. In the resistance exercise group, there was an increase in the arm muscle circumference from 233.6 (IQR 202-254) mm to 241.4 (IQR 203-264) mm (P= .001), arm muscle area from 35.9 (26-41) cm(2) to 36.6 (IQR 26-46) cm(2) (P= .002), and handgrip strength from 19.6 (IQR 11-28) kg to 21.2 (IQR 13-32) kg between the basal and final measurements (P < .05). The tolerance to exercise was adequate, and no adverse events were reported during the practical exercise. CONCLUSIONS: Resistance exercise at least twice a week is safe and represents an opportunity for improving the muscle mass and strength in adult patients who are on hemodialysis, including in those with malnutrition. PMID- 26264175 TI - Discrimination of driver and passenger mutations in epidermal growth factor receptor in cancer. AB - Cancer is one of the most life-threatening diseases and mutations in several genes are the vital cause in tumorigenesis. Protein kinases play essential roles in cancer progression and specifically, epidermal growth factor receptor (EGFR) is an important target for cancer therapy. In this work, we have developed a method to classify single amino acid polymorphisms (SAPs) in EGFR into disease causing (driver) and neutral (passenger) mutations using both sequence and structure based features of the mutation site by machine learning approaches. We compiled a set of 222 features and selected a set of 21 properties utilizing feature selection methods, for maximizing the prediction performance. In a set of 540 mutants, we obtained an overall classification accuracy of 67.8% with 10 fold cross validation using support vector machines. Further, the mutations have been grouped into four sets based on secondary structure and accessible surface area, which enhanced the overall classification accuracy to 80.2%, 81.9%, 77.9% and 75.1% for helix, strand, coil-buried and coil-exposed mutants, respectively. The method was tested with a blind dataset of 60 mutations, which showed an average accuracy of 85.4%. These accuracy levels are superior to other methods available in the literature for EGFR mutants, with an increase of more than 30%. Moreover, we have screened all possible single amino acid polymorphisms (SAPs) in EGFR and suggested the probable driver and passenger mutations, which would help in the development of mutation specific drugs for cancer treatment. PMID- 26264174 TI - Quantitative assessment of non-motor fluctuations in Parkinson's disease using the Non-Motor Symptoms Scale (NMSS). AB - Data on frequency, severity and correlations of NMS with motor complications are only available for a limited number of NMS. The NMS Scale (NMSS) is a validated tool to assess a broad range of NMS, which has not been used in NMS fluctuations. We assessed fluctuations of a broad range of non-motor symptom (NMS) for a 1 month time period in fluctuating Parkinson's disease (PD) in a multicenter cross sectional study using the NMSS assessing NMS in motor On (NMSSOn) and Off state (NMSSOff) combined with clinical NMS and motor function scoring in 100 fluctuating PD patients. DeltaNMSSOn/Off was defined as the differences of NMSS scores between On and Off. Complete NMSS datasets were available from 73 patients (53 % men; age: 68.2 +/- 9.7 years) with mean total NMSS score in On state of 41.5 +/- 37.6 and in Off state of 75.6 +/- 42.3 (P < 0.001). Scores were higher in Off compared to On state for all domains except for domain "perceptual problems/hallucinations" (P = 0.608). Clinimetric properties of the NMSS were similar to those reported previously for NMS assessments independent of motor oscillations. NMSSOn, NMSSOff and DeltaNMSSOn/Off showed weak to moderate correlations with demographics, indicators of motor symptom severity as well as with other measures of NMS, depression and quality of life. Correlations of NMSS items/domains with independent measures of related constructs were weak to moderate. In conclusion, when assessed with the NMSS, a broad range of NMS fluctuate with motor oscillations, but these fluctuations do neither correlate with motor function nor with measures of disease progression. PMID- 26264176 TI - Posttraumatic Total Knee Arthroplasty Continues to Have Worse Outcome Than Total Knee Arthroplasty for Osteoarthritis. AB - Small studies have shown that patients who undergo TKA following a distal femur and/or tibial plateau fracture have inferior results. The purpose of this study was to evaluate the mid-term outcomes of a large group of patients undergoing TKA following periarticular knee fractures. We identified 531 patients who underwent a TKA following a periarticular fracture from 1990 to 2012; comparing outcomes to 19,641 patients undergoing primary TKA for osteoarthritis. Periarticular fracture significantly increased the risk of revision TKA, infection and complications. There was no difference in the need for revision TKA or infection based on fracture location. Patients with TKA following a periarticular fracture have worse overall revision free survival compared to with OA, with 1 in 4 patients requiring revision TKA by 15 years. PMID- 26264177 TI - Total Hip Arthroplasty after Previous Acetabular Osteotomy: Comparison of Three Types of Acetabular Osteotomy. AB - To compare surgical results of total hip arthroplasty (THA) following acetabular osteotomy, operative records of 13 hips following Chiari osteotomy (Chiari group), 22 hips following rotational periacetabular osteotomy (RAO; RAO group), 16 hips following shelf acetabuloplasty (Shelf group), and 2475 hips without previous osteotomy (Control group) were retrospectively reviewed. The operative time was significantly longer in the RAO group than in the Control group. Bulk bone augmentation was required more often in the Chiari and RAO groups than in the Control group. An early migration of the acetabular cup occurred in 2 hips in the RAO group. RAO made conversion to THA more complicated than did the Chiari osteotomy or the shelf acetabuloplasty. PMID- 26264178 TI - Comparison of Alignment Correction Angles Between Fixed-Bearing and Mobile Bearing UKA. AB - Good outcomes have been reported with both fixed-bearing and mobile-bearing unicompartmental knee arthroplasty (UKA). However, overcorrected alignment could induce the progression of arthritis on the non-arthroplasty side. Changes of limb alignment after UKA with both types of bearings (fixed bearing: 24 knees, mobile bearing: 28 knees) were investigated. The mean difference between the preoperative standing femoral-tibial angle (FTA) and postoperative standing FTA was significantly larger in mobile bearing UKA group. In fixed-bearing UKA, there must be some laxity in MCL tension so that a 2-mm tension gauge can be inserted. In mobile-bearing UKA, appropriate MCL tension is needed to prevent bearing dislocation. This difference in MCL tension may have caused the difference in the correction angle between the groups. PMID- 26264179 TI - Limitations of the Vastus Lateralis Muscle as a Substitute for Lost Abductor Muscle Function: An Anatomical Study. AB - Abductor insufficiency after hip arthroplasty resulting from an impaired gluteus medius and minimus remains an unsolved problem in orthopaedic surgery. The vastus lateralis (VL) was described as a functional substitute for abductor insufficiency in 2004. We carried out a macrodissection of twelve cadaveric hemipelvises to investigate the innervation of the VL and adjacent muscles to assess the extent the VL can be safely transferred. Results showed that direct muscle branches to proximal portions of the VL are too short to allow a significant shift; the shift may be as small as 13 mm. Nerves that supply the VL also extend to the vastus intermedius. This innervation pattern makes it impossible to shift the VL significantly without damaging branches to both. PMID- 26264180 TI - The effects of experimental knee pain on lower limb corticospinal and motor cortex excitability. AB - INTRODUCTION: Notable weakness of the quadriceps muscles is typically observed as a consequence of knee joint arthritis, knee surgery and knee injury. This is partly due to ongoing neural inhibition that prevents the central nervous system from fully activating the quadriceps, a process known as arthrogenic muscle inhibition (AMI). To investigate the mechanisms underlying AMI, this study explored the effects of experimental knee pain on lower limb corticospinal and motor cortex excitability. METHODS: Twenty-four healthy volunteers participated in this study. In experiment 1, experimental knee pain was induced by the injection of hypertonic saline into the infrapatellar fat pad (n = 18). In experiment 2, isotonic saline was injected into the fat pad as a non-painful control (n = 8). Pain intensity was measured on a 10-cm electronic visual analogue scale. Transcranial magnetic stimulation and electromyography were used to measure lower limb motor-evoked potential amplitude and short-interval intracortical inhibition before and after the injection. RESULTS: The peak VAS score following hypertonic saline (5.0 +/- 0.5 cm) was higher than after isotonic saline (p <0.001). Compared with baseline, there was a significant increase in vastus lateralis (p = 0.02) and vastus medialis motor-evoked potential amplitude (p = 0.02) during experimental knee pain that was not apparent during the control condition. Biceps femoris and tibialis anterior motor-evoked potential amplitude did not change following injection (all p >0.05). There was no change in short interval intracortical inhibition measured from vastus lateralis following injection (both p >0.05). CONCLUSIONS: Quadriceps corticospinal excitability increases during experimental knee pain, providing no evidence for a supraspinal contribution to quadriceps AMI. PMID- 26264181 TI - Myeloid cell leukemia 1 (Mcl(-1)) protects against 1-methyl-4-phenylpyridinium ion (MPP+) induced apoptosis in Parkinson's disease. AB - The myeloid cell leukemia 1 (Mcl(-1)) is an anti-apoptotic member of the Bcl-2 family, which plays an essential role in protecting cells against apoptosis. The expression pattern and potential roles of Mcl(-1) in Parkinson's diseases (PD) are still unknown. In this study, our results indicated that 1-methyl-4 phenylpyridinium (MPP+) treatment augmented the expression of Mcl(-1) at both messenger RNA (mRNA) and protein levels in a dose-dependent manner in SH-SY5Y cells. Moreover, we observed increased phosphorylation of Elk-1at Ser383 as well as nuclear translocation of Elk-1 in exposure to MPP+ treatment. Importantly, the elevated expression of Mcl(-1) induced by MPP+ was abolished by knockdown of Elk 1. It was also found that inhibition of Mcl(-1) by small RNA transfection exacerbates MPP + -induced LDH release after 48 h incubation. In addition, Hoechst 33,258 nuclear staining results demonstrated that silence of Mcl(-1) induced a significant increase in apoptosis in cells when compared with the control condition. Mechanistically, the levels of cleaved Caspase3 and PARP were elevated in MPP+ treated cells, which was exacerbated by knockdown of Mcl(-1). These findings suggest that Mcl(-1) might be a potential therapeutic target for PD treatment. PMID- 26264182 TI - Mesenchymal stromal cells are genetically stable under a hostile in vivo-like scenario as revealed by in vitro micronucleus test. AB - BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) have elicited a great hope in the field of regenerative medicine because of their high therapeutic potential in treating several disorders. Therefore, from the clinical point of view, it is essential to understand genetic stability and survival of MSCs under different in vivo scenarios. Recently, we have reported nuclear blebs and micronuclei as a marker of genetic instability in MSCs. METHODS: In our present study, we exposed umbilical cord MSCs and placenta-derived MSCs to diverse conditions simulating an in vivo scenario and studied their genetic stability by use of an in vitro micronucleus test. RESULTS: We observed that a sudden decrease in oxygen concentration led to an increase in the number of nuclear blebs and decrease in proliferation rate without inducing senescence. Moreover, we also observed that 2.5% hypoxia exerted a markedly different pattern of regulation of various cell cycle checkpoint genes such as hypoxia-inducible factor-1alpha (HIF-1alpha), ataxia telangiectasia mutated (ATM), ataxia telangiectasia and Rad3 related (ATR), p53, p21, p27 and p21 than did 5% hypoxia. It is interesting to note that the MSCs were genetically stable under hyperglycemic and ischemic conditions and underwent quiescence on serum starvation accompanied by hypoxia. We also tested the genotoxicity of conditioned media derived from adverse conditions and observed that it did not result in genetic instability. CONCLUSIONS: Our data demonstrate for the first time that umbilical MSCs and placenta-derived MSCs are genetically stable under hostile in vivo situations, indicating their suitability for therapeutic purposes. PMID- 26264183 TI - Monitoring microbial metabolites using an inductively coupled resonance circuit. AB - We present a new approach to monitor microbial population dynamics in emulsion droplets via changes in metabolite composition, using an inductively coupled LC resonance circuit. The signal measured by such resonance detector provides information on the magnetic field interaction with the bacterial culture, which is complementary to the information accessible by other detection means, based on electric field interaction, i.e. capacitive or resistive, as well as optical techniques. Several charge-related factors, including pH and ammonia concentrations, were identified as possible contributors to the characteristic of resonance detector profile. The setup enables probing the ionic byproducts of microbial metabolic activity at later stages of cell growth, where conventional optical detection methods have no discriminating power. PMID- 26264184 TI - Six principles to enhance health workforce flexibility. AB - This paper proposes approaches to break down the boundaries that reduce the ability of the health workforce to respond to population needs, or workforce flexibility. Accessible health services require sufficient numbers and types of skilled workers to meet population needs. However, there are several reasons that the health workforce cannot or does not meet population needs. These primarily stem from workforce shortages. However, the health workforce can also be prevented from responding appropriately and efficiently because of restrictions imposed by professional boundaries, funding models or therapeutic partitions. These boundaries limit the ability of practitioners to effectively diagnose and treat patients by restricting access to specific skills, technologies and services. In some cases, these boundaries not only reduce workforce flexibility, but they introduce inefficiencies in the form of additional clinical transactions and costs, further detracting from workforce responsiveness. Several new models of care are being developed to enhance workforce flexibility by enabling existing staff to work to their full scope of practice, extend their roles or by introducing new workers. Expanding on these concepts, this theoretical paper proposes six principles that have the potential to enhance health workforce flexibility, specifically: 1. Measure health system performance from the perspective of the patient. 2. Minimise training times. 3. Regulate tasks (competencies), not professions. 4. Match rewards and indemnity to the levels of skill and risk required to perform a particular task, not professional title. 5. Ensure that practitioners have all the skills they need to perform the tasks required to work in the environment in which they work 6. Enable practitioners to work to their full scope of practice delegate tasks where required These proposed principles will challenge some of the existing social norms around health-care delivery; however, many of these principles are already being applied, albeit on a small scale. This paper discusses the implications of these reforms. PROPOSED DISCUSSION POINTS: 1. Is person-centred care at odds with professional monopolies? 2. Should the state regulate professions and, by doing so, protect professional monopolies or, instead, regulate tasks or competencies? 3. Can health-care efficiency be enhanced by reducing the number of clinical transactions required to meet patient needs? PMID- 26264185 TI - Readout-segmented echo-planar diffusion-weighted imaging improves geometric performance for image-guided radiation therapy of pelvic tumors. AB - BACKGROUND AND PURPOSE: Diffusion-weighted imaging using echo-planar imaging (EPI) is prone to geometric inaccuracy, which may limit application to image guided radiation therapy planning, as well as for voxel-based quantitative multi parametric or multi-modal approaches. This research investigates pelvic applications at 3 T of a standard single-shot (ssEPI) and a prototype readout segmented (rsEPI) technique. MATERIALS AND METHODS: Apparent diffusion coefficient (ADC) accuracy and geometric performance of rsEPI and ssEPI were compared using phantoms, and in vivo, involving 8 patients prior to MR-guided brachytherapy for locally advanced cervical cancer, and 19 patients with prostate cancer planned for tumor-targeted radiotherapy. Global and local deviations in geometric performance were tested using Dice Similarity Coefficients (DC) and Hausdorff Distances (HD). RESULTS: In cervix patients, DC increased from 0.76+/ 0.14 to 0.91+/-0.05 for the high risk clinical target volume, and 0.62+/-0.26 to 0.85+/-0.08 for the gross tumor target volume. Tumors in the peripheral zone of the prostate gland were partly projected erroneously outside of the posterior anatomic boundary of the gland by 3.1+/-1.6 mm in 11 of 19 patients using ADC ssEPI but not with ADC-rsEPI. CONCLUSIONS: Both cervix and prostate ssEPI are prone to clinically relevant geometric distortions at 3T. rsEPI provides improved geometric performance without post-processing. PMID- 26264187 TI - Cyclic polymers revealing topology effects upon self-assemblies, dynamics and responses. AB - A variety of single- and multicyclic polymers having programmed chemical structures with guaranteed purity have now become obtainable owing to a number of synthetic breakthroughs achieved in recent years. Accordingly, a broadening range of studies has been undertaken to gain updated insights on fundamental polymer properties of cyclic polymers in either solution or bulk, in either static or dynamic states, and in self-assemblies, leading to unusual properties and functions of polymer materials based on their cyclic topologies. In this article, we review recent studies aiming to achieve distinctive properties and functions by cyclic polymers unattainable by their linear or branched counterparts. We focus, in particular, on selected examples of unprecedented topology effects of cyclic polymers upon self-assemblies, dynamics and responses, to highlight current progress in Topological Polymer Chemistry. PMID- 26264186 TI - Inhibition of ZEB1 expression induces redifferentiation of adult human beta cells expanded in vitro. AB - In-vitro expansion of functional adult human beta-cells is an attractive approach for generating insulin-producing cells for transplantation. However, human islet cell expansion in culture results in loss of beta-cell phenotype and epithelial mesenchymal transition (EMT). This process activates expression of ZEB1 and ZEB2, two members of the zinc-finger homeobox family of E-cadherin repressors, which play key roles in EMT. Downregulation of ZEB1 using shRNA in expanded beta-cell derived (BCD) cells induced mesenchymal-epithelial transition (MET), beta-cell gene expression, and proliferation attenuation. In addition, inhibition of ZEB1 expression potentiated redifferentiation induced by a combination of soluble factors, as judged by an improved response to glucose stimulation and a 3-fold increase in the fraction of C-peptide-positive cells to 60% of BCD cells. Furthermore, ZEB1 shRNA led to increased insulin secretion in cells transplanted in vivo. Our findings suggest that the effects of ZEB1 inhibition are mediated by attenuation of the miR-200c target genes SOX6 and SOX2. These findings, which were reproducible in cells derived from multiple human donors, emphasize the key role of ZEB1 in EMT in cultured BCD cells and support the value of ZEB1 inhibition for BCD cell redifferentiation and generation of functional human beta like cells for cell therapy of diabetes. PMID- 26264188 TI - Label-free photoelectrochemical cytosensing via resonance energy transfer using gold nanoparticle-enhanced carbon dots. AB - A universal and label-free photoelectrochemical cytosensing strategy was designed based on resonance energy transfer (RET) between carbon dots and cysteamine capped gold nanoparticles. RET promoted photo-to-current conversion efficiency and enhanced detection sensitivity. This proposed photoelectrochemical cytosensing platform exhibited a good performance for the assay of tumor cells with overexpressed receptors on cells. PMID- 26264189 TI - Improved determination of dynamic balance using the centre of mass and centre of pressure inclination variables in a complete golf swing cycle. AB - Golf requires proper dynamic balance to accurately control the club head through a harmonious coordination of each human segment and joint. In this study, we evaluated the ability for dynamic balance during a golf swing by using the centre of mass (COM)-centre of pressure (COP) inclination variables. Twelve professional, 13 amateur and 10 novice golfers participated in this study. Six infrared cameras, two force platforms and SB-Clinic software were used to measure the net COM and COP trajectories. In order to evaluate dynamic balance ability, the COM-COP inclination angle, COM-COP inclination angular velocity and normalised COM-COP inclination angular jerk were used. Professional golfer group revealed a smaller COM-COP inclination angle and angular velocity than novice golfer group in the lead/trail direction (P < 0.01). In the normalised COM-COP inclination angular jerk, the professional golfer group showed a lower value than the other two groups in all directions. Professional golfers tend to exhibit improved dynamic balance, and this can be attributed to the neuromusculoskeletal system that maintains balance with proper postural control. This study has the potential to allow for an evaluation of the dynamic balance mechanism and will provide useful basic information for swing training and prevention of golf injuries. PMID- 26264190 TI - Estimation of 2D strain in abdominal organs during an impact based on ultrafast ultrasound images: a physical landmark-based approach. PMID- 26264191 TI - Giant spin thermoelectric effects in all-carbon nanojunctions. AB - We examine the thermospin properties of an all-carbon nanojunction constructed by a graphene nanoflake (GNF) and zigzag-edged graphene nanoribbons (ZGNRs), bridged by the carbon atomic chains. The first-principles calculations show that the phonon thermal conductance is much weaker than the electron thermal conductance at the Fermi level, and even the former is a few percent of the latter in the low temperature regime. In the meantime, the carbon-based device possesses an excellent spin transport property at the Fermi level due to the appearance of half-metallic property. Furthermore, the single-spin Seebeck coefficient has a larger value at the Fermi level. These facts ultimately result in a significant enhancement of spin thermoelectric figure of merit (FOM) ZST. By controlling the carbon-chain lengths and the temperature, the maximal value of ZST can reach 30. Moreover, we also find that the room temperature ZST displays an odd-even effect with the carbon-chain lengths, and it is always larger than the charge thermoelectric FOM ZCT. PMID- 26264192 TI - The photochemical mechanism of a B12-dependent photoreceptor protein. AB - The coenzyme B12-dependent photoreceptor protein, CarH, is a bacterial transcriptional regulator that controls the biosynthesis of carotenoids in response to light. On binding of coenzyme B12 the monomeric apoprotein forms tetramers in the dark, which bind operator DNA thus blocking transcription. Under illumination the CarH tetramer dissociates, weakening its affinity for DNA and allowing transcription. The mechanism by which this occurs is unknown. Here we describe the photochemistry in CarH that ultimately triggers tetramer dissociation; it proceeds via a cob(III)alamin intermediate, which then forms a stable adduct with the protein. This pathway is without precedent and our data suggest it is independent of the radical chemistry common to both coenzyme B12 enzymology and its known photochemistry. It provides a mechanistic foundation for the emerging field of B12 photobiology and will serve to inform the development of a new class of optogenetic tool for the control of gene expression. PMID- 26264193 TI - Stable analogues of nojirimycin--synthesis and biological evaluation of nojiristegine and manno-nojiristegine. AB - Two novel iminosugars called nojiristegines, being structural hybrids between nor tropane alkaloid calystegine and nojirimycins, have been synthesised and found to be stable molecules despite the presence of a hemiaminal functionality. The synthesised iminosugars were evaluated against a panel of glycosidases and the best inhibition (IC50), found against alpha-glucosidases, was in the micromolar region. The compounds were also evaluated as potential antibiotics but no useful level of activity was observed. PMID- 26264194 TI - Nanomedical strategies for targeting skin microbiomes. AB - Nanoparticles can be effective drug delivery systems for treating bacterial and fungal infections in the skin. The nanoparticles used for drug therapy give many advantages over conventional formulations, such as increased solubility and storage stability, improved permeability and bioavailability, prolonged half life, tissue targeting, and minimal side effects. In recent years, the concept of using nanoparticles to treat skin-microbiomerelated diseases has attracted increasing attention. This review article aimed to introduce recent progress using nanomedical strategies for drug delivery. Various modalities of nanocarriers can be used for antimicrobial therapy of disease, including liposomes, microemulsions, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and polymeric nanoparticles. This review systematically describes the structures and physicochemical properties of different nanocarriers, emphasizing antibacterial activity of nanoparticles for inhibiting infection. Nanoparticles for treating appendageal bacteria have gained attention in recent years, in particular, nanomedical approaches for managing acne. Issues related to the treatment of non-appendageal bacteria and fungi are also discussed. Finally, current obstacles to using nanocarriers for delivering medicines aimed at inhibiting infection and future developments are addressed. PMID- 26264195 TI - Propionibacterium acnes in the pathogenesis and immunotherapy of acne vulgaris. AB - Acne vulgaris, a multi-factorial disease, is one of the most common skin diseases, affecting an estimated 80% of Americans at some point during their lives. The gram-positive and anaerobic Propionibacterium acnes (P. acnes) bacterium has been implicated in acne inflammation and pathogenesis. Therapies for acne vulgaris using antibiotics generally lack bacterial specificity, promote the generation of antibiotic-resistant bacterial strains, and cause adverse effects. Immunotherapy against P. acnes or its antigens (sialidase and CAMP factor) has been demonstrated to be effective in mice, attenuating P. acnes induced inflammation; thus, this method may be applied to develop a potential vaccine targeting P. acnes for acne vulgaris treatment. This review summarizes reports describing the role of P. acnes in the pathogenesis of acne and various immunotherapy-based approaches targeting P. acnes, suggesting the potential effectiveness of immunotherapy for acne vulgaris as well as P. acnes-associated diseases. PMID- 26264196 TI - Characterization of fungal and bacterial components in gut/fecal microbiome. AB - The gut microbiota is a complex ecosystem that affects the development, nutritional status and immunological responses of the host. Prokaryotes and fungi in the community have the abilities to withstand the adverse conditions of high temperature, low oxygen etc. and to decompose complex organic molecules. The novel approaches of metagenomics and metaproteomics provide data that allow the detection of patterns of constancy or changes in time or under different conditions, such as different diets, disease condition and antibiotic therapy. These large-scale patterns can be correlated with certain health or disease conditions. From the organismic point of view, however, the species identity of the organisms and their interactions in the gut and how these interactions influence the prevention or development of disease are poorly known. The diversity and roles of fungi in animal feces appear to be better known than in human gut/feces. A combined compilation of the diverse methods applied towards prokaryotes and fungi in the gut/feces microbiome serves as a base for meeting the challenges of masses of large-scale datasets on the one hand and lack of substantial organismic understanding on the other. Starting from long-term monitoring and large-scale characterization of the composition of microbiome from systematic higher groups down to the genus level, microbial genomes and proteomes, particular key components with antimicrobial or immune functions can be selected and investigated in detail with respect to understanding of host microbiota interaction, disease pathogenesis and developing diagnostic and therapeutic tools. PMID- 26264197 TI - Mass Spectrometry Imaging: Applications in Drug Distribution Studies. AB - In the past decade, mass spectrometry imaging (MSI) has received an increasing amount of attention due to its ability in displaying the spatial distribution of a wide range of molecules, including peptides, proteins, lipids, endogenous and exogenous metabolites, and xenobiotics in biological tissues. Information regarding drug localization within tissues provides a better understanding of pharmacokinetic behaviors and pharmacological and toxicological effects. This review presents an introduction to MSI, along with an in-depth analysis of its general process. In addition, we highlighted several examples of various intensive applications of imaging drugs and metabolites in tissues by mass spectrometry. Furthermore, we present the prospect of quantitative MSI of small molecular chemicals, which may be particularly attractive to researchers in the pharmaceutical industry today. It is expected that with technological advancement, MSI will become an increasingly powerful tool in drug disposition studies and other fields of biomedical research. PMID- 26264198 TI - Interactions between Transporters and Herbal Medicines/Drugs: A Focus on Hepatoprotective Compounds. AB - Many herbal medicines and drugs are available in the clinic as potent hepatoprotective agents for the treatment of commonly occurring liver diseases. Recently, herbal medicines such as silymarin and curcumin have gained more attention and popularity for the treatment of various liver diseases because of their safety and efficacy profiles. Some of them are related to transporters for drug disposition processes, therapeutic efficacy and/or adverse drug reactions. Currently, herbal medicines and diet supplements made from natural products are widely used in patients who are being treated with conventional prescription medicines, which are related to an increasing risk of herbal-drug interactions (HDIs) and/or drug-drug interactions (DDIs). The purpose of present review is to summarize the contemporary knowledge of transporter-mediated HDIs or DDIs for herbal medicines/drugs focusing on hepatoprotective compounds. Several herbal medicines/drugs are discussed in detail in this review. PMID- 26264199 TI - Theory and Application of Microdialysis in Pharmacokinetic Studies. AB - The major aim of current pharmacokinetic studies is to investigate the drug absorption, disposition, metabolism and excretion in animals and humans. The time courses of plasma concentrations are usually characterized and linked to the pharmacodynamic effect to evaluate drug efficacy. However, under certain circumstance, site of action is located in tissues rather than in circulation, which requires direct measurement of tissue concentrations instead of plasma concentrations. Microdialysis is one of those techniques that have been demonstrated to be feasible for measurement of free drug concentration in many tissues, and is capable of being applied in most pharmacokinetic studies to enhance drug efficacy and reduce the unnecessary side effects. This paper reviews this technique from the perspective of theoretical background including the history of development, basic principle, components and their functions. Moreover, the relative recovery of microdialysis and the key factors are discussed, followed by calibration methods available to reduce the systemic bias. In addition, microdialysis is compared with conventional tissue sampling technique for superiorities and limitations. At last, the application of microdialysis in pharmacokinetic study is summarized, especially in assessment of drug efficacy and safety in different tissues. So far, microdialysis is a valuable tool in drug development and will play an unique role in a variety of pharmacokinetic and pharmacodynamic studies in future. PMID- 26264200 TI - Physiologically Based In vitro Models to Predict the Oral Dissolution and Absorption of a Solid Drug Delivery System. AB - To understand the sophisticated dynamic behaviors of drug elution and permeation in the gastrointestinal tract (GIT), researchers have tried to reemerge it by employing various in vitro experimental models. However, official in vitro apparatuses routinely used for quality control purposes, employ simple, non physiologic buffers, and hydrodynamics conditions, and can not accurately perform continuous, dynamic in vivo pharmacokinetics (PK) behaviors. Therefore, different angles of GI physiology information are incorporate into novel models to forecast the dissolution and permeation of drug solid dosage forms. This review, in general, discusses some related studies of physiologically-based mechanical models to predict human absorption following oral administration in four sections. First the GIT, taken out of a complex physiological environment, where the drug is absorbed, distributed, metabolized and excreted (ADME) in the human body, is considered as the physiological basis for active pharmaceutics ingredients (API) dissolved and permeated through the epithelial cell. The second part embodies the theoretical foundation of in vitro models to predict human absorption and the corresponding in vitro.in vivo correlations (IVIVC). The third section summarizes physiologically based dissolution models developed recently, ranging from dynamic compartmental dissolution models, to biorelevant dissolution models based on certain physiological factors, to biphasic dissolution models. The last part is devoted to combined dissolution and absorption models that can be employed to simulate the continuous, dynamic behavior of oral drug delivery being dissolved and subsequently permeated across the GIT. Along with physiologically-based mechanically models spring up, pharmaceutical researchers will harvest better level A IVIVC for oral drug delivery systems, especially for sustained and controlled release preparations. On the other way hand, it will successively promote more effective bionic models to optimize prescription, design formulation, and develop innovative products. PMID- 26264201 TI - Adverse Drug Reactions to Anti-TB Drugs: Pharmacogenomics Perspective for Identification of Host Genetic Markers. AB - Adverse drug reactions (ADRs) are associated with clinical morbidity and, in severe cases, even mortality. Globally billions of dollars are spent on managing these ADRs for common and uncommon diseases. The developing world suffers from a high burden of tuberculosis, which requires 6-8 months of multi-drug treatment. In spite of most cases being treatable the problem persists mainly due to a high attrition rate associated with ADR mediated complications. Due to these reasons drug resistant strains have emerged and are now a serious challenge to TB eradication. To effectively deliver the available treatment regimen and ensure patient compliance it is important to manage ADRs more efficiently. Recent studies have demonstrated that drug outcomes are patient-specific and can, therefore be predicted. A few of these drugs, including a few administered for TB, have shown excellent correlation with response rates and development of ADRs. In this review, we profile information available in public domain for existing anti-TB drugs to understand the genesis of ADRs and patient response. Additionally, human genome variation databases have been used to correlate the frequency of these markers and their genomic variants in different populations. PMID- 26264203 TI - Emerging Strategies and Challenges for Controlled Delivery of Taxanes: A Comprehensive Review. AB - Taxanes introduction in the mid 90 s leads to significant advancement as well as superlative improvement in the treatment of cancer. Since then, several strategies have been designed to enhance therapeutic potential of these agents by overcoming the limitations in drug delivery and pharmacokinetic constraints associated with conventional delivery. In this regard, controlled drug delivery systems for taxanes have contributed enormously by altering the pharmacokinetic profile, thus ultimately enhancing their therapeutic response. With their conferred stellar merits, controlled drug delivery systems have been able to surmount many of the challenges associated with conventional drug delivery systems. The altered absorption, resistance, low toxicity and cellular uptake profiles that lead to better safety from variegated carrier systems like nanocarriers, liposomes, solid lipid nanoparticles, nanoemulsions, nanocapsules, hydrogels and micelles for controlled delivery of taxanes call for an exhaustive review for future progressive work. Therefore, this review focuses on the altered pharmacokinetic, pharmacodynamic and toxicity patterns achieved from various controlled drug delivery approaches, with the latter half highlighting the clinical profile set ups and commercial aspects of controlled release drug delivery systems. PMID- 26264204 TI - Magnetic Nanoparticles: Properties, Synthesis and Biomedical Applications. AB - Importance of magnetic nanoparticles in daily life including biomedical applications in near future cannot be overlooked. This review focuses on the properties of magnetic nanoparticles (MNPs), various approaches for their synthesis, and their biomedical applications. First part of this review focuses on the classes, physical properties, and characteristics of MNPs. The second part sheds light on strategies developed for the synthesis of MNPs, with special attention given to biological, physical, and chemical approaches as well as recent modifications in the preparation of monodispersed samples. Furthermore, this review deals with the biomedical applications of MNPs, which includes applications in targeted drug delivery, diagnostics, gene therapy, hyperthermia and advantages in the field of medicine. PMID- 26264205 TI - Nanoparticles, Neurotoxicity and Neurodegenerative Diseases. AB - Our modern era is witnessing an increased prevalence of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease and brain tumors. This is accompanied by an increased production of nanoparticles (NPs) and the subsequent release of NPs in the environment shared by humans. NPs are extremely small molecules measuring about 100 nm in diameter. Due to minuscule size, NPs have the potential to penetrate human body through various pathways and eventually cross the blood-brain barrier to potentially cause neurotoxicity, neuroinflammation and neurodegeneration of the central nervous system. Until recently, the mechanisms by which NPs cause neuroinflammation and neurodegeneration were unknown. However, recent in vivo, ex vivo and in vitro studies have significantly advanced our understanding of the mechanisms by which NPs may cause neurotoxicity and neurodegeneration. In light of this understanding, various pathways have been identified as the basic mechanisms by which NPs cause damage in the brain. The goal of this review is to summarize new mechanistic findings and different pathways of NP-induced neurotoxicity. Better knowledge of such pathways can lead researchers to devise effective therapeutic strategies for neuroprotection against nanoparticles. PMID- 26264206 TI - Solid Matrix Based Lipidic Nanoparticles in Oral Cancer Chemotherapy: Applications and Pharmacokinetics. AB - Chemotherapeutic delivery by oral route in cancer patients has the potential to create "hospitalization free chemotherapy" which is a vision of oncologists, formulation scientists and patients. Such a therapeutic approach will improve patients' compliance, ease the burden of the patients' caregivers and significantly reduce the cost of treatment. In current clinical practice, chemotherapy carried out by intravenous injection or infusion leads to undesired side-effects such as plasma concentrations crossing the maximum safe concentration, rapid body clearance and lower bioavailability. Despite the presence of challenges such as poor aqueous solubility and stability of drugs and the presence of biological barriers like multidrug efflux transporter in the GI tract, oral cancer chemotherapy has the potential to surmount those obstacles. Lipid nanoparticles (LNPs) such as solid lipid nanoparticle, nanostructured lipid carriers, nano lipid-drug conjugates, mixed micelles, liposomes and nanoemulsions have shown some promising results for use in oral anticancer drug delivery through nanotechnological approach. LNPs demonstrate enhanced oral bioavailability owing to their ability to inhibit first pass metabolism via lymphatic absorption by chylomicron-linked and/or M-cell uptake. LNPs reduce the inter- and intrasubject pharmacokinetics variability of administrated drugs. Moreover, certain classes of phospholipids and surfactants used in the formulations of LNPs can suppress the P-glycoprotein efflux system. Here, we shall be discussing the biopharmaceutical challenges in oral cancer chemotherapy and how the LNPs may provide solutions to such challenges. The effect of GI tract environment on LNPs and pharmacokinetics shall also be discussed. PMID- 26264207 TI - The Ins and Outs of Nanoparticle Technology in Neurodegenerative Diseases and Cancer. AB - As we enter the twenty-first century, several therapies based on using nanoparticles (NPs) ranging in size 1 - 1000 nm have been successfully brought to the clinic to treat cancer, pain and infectious diseases. These therapies bring together the ability of NPs to target the delivery of drugs more precisely, to improve solubility, to prevent degradation, to improve their therapeutic index and to reduce the immune response. NPs come in all shapes and sizes, designed specifically for biomedical applications such as solid lipid polymers, liposomes, dendrimers, nanogels, and quantum dots. These NPs offer many attractive characteristics such as biological stability and biocompatibility, thus incorporating different biological or drug molecules. Among the major therapeutic challenges from neurological diseases through to cancer is the development of nanomaterials that are able to be effective against the disease. In the case of neurodegeneration, one of the most difficult areas to penetrate for drug discovery in the body is the central nervous system, protected by the blood-brain barrier. Whilst in the case of cancer, the biggest problem is how to specifically target a tumor with sufficient drug without causing side effects or inducing resistance. A new generation of intelligent NPs are emerging for the treatment of human disease such as neurological disorders and cancer. The use of natural alternative therapy is an encouraging idea in drug discovery. To this end as we gain more knowledge into the biological function of exosomes, this will allow us to harness their potential as natural NPs in future therapeutics. PMID- 26264202 TI - Diallyl Sulfide: Potential Use in Novel Therapeutic Interventions in Alcohol, Drugs, and Disease Mediated Cellular Toxicity by Targeting Cytochrome P450 2E1. AB - Diallyl sulfide (DAS) and other organosulfur compounds are chief constituents of garlic. These compounds have many health benefits, as they are very efficient in detoxifying natural agents. Therefore, these compounds may be useful for prevention/treatment of cancers. However, DAS has shown appreciable allergic reactions and toxicity, as they can also affect normal cells. Thus their use as in the prevention and treatment of cancer is limited. DAS is a selective inhibitor of cytochrome P450 2E1 (CYP2E1), which is known to metabolize many xenobiotics including alcohol and analgesic drugs in the liver. CYP2E1-mediated alcohol/drug metabolism produce reactive oxygen species and reactive metabolites, which damage DNA, protein, and lipid membranes, subsequently causing liver damage. Several groups have shown that DAS is not only capable of inhibiting alcohol- and drug-mediated cellular toxicities, but also HIV protein- and diabetes-mediated toxicities by selectively inhibiting CYP2E1 in various cell types. However, due to known DAS toxicities, its use as a treatment modality for alcohol/drug- and HIV/diabetes-mediated toxicity have only limited clinical relevance. Therefore, effort is being made to generate DAS analogs, which are potent and selective inhibitor of CYP2E1 and poor substrate of CYP2E1. This review summarizes current advances in the field of DAS, its anticancer properties, role as a CYP2E1 inhibitor, preventing agent of cellular toxicities from alcohol, analgesic drugs, xenobiotics, as well as, from diseases like HIV and diabetes. Finally, this review also provides insights toward developing novel DAS analogues for chemical intervention of many disease conditions by targeting CYP2E1 enzyme. PMID- 26264208 TI - In my end is my beginning: developmental trajectories of adverse childhood experiences to late-life suicide. AB - OBJECTIVES: Converging evidence suggests that the sequelae of adverse childhood experiences (ACEs) including childhood abuse (e.g., sexual, physical, emotional/verbal abuse, neglect) and other ACE (e.g., family dysfunction, parental loss, parental psychopathology, substance abuse, incarceration, and domestic violence) have pronounced effects on suicidal behaviors (suicidal ideation, attempts, and death by suicide) in older age. There are fundamental changes in the developmental trajectory of biological, psychological and behavioral processes that result from ACE and that exert influence throughout the life span. Different moderators and mediators may affect the extent and nature of the relationship. However, the literature on the specific mechanisms whereby ACE affects suicidality in later life has not been well identified. METHOD: We review and draw from extant multidisciplinary evidence to develop a heuristic framework through which to understand how ACE may lead to suicide in later life. RESULTS: Proposed mechanisms span biological factors (neurological, gene-environment), psychiatric and health functioning, and psychosocial development (cognitive biases, coping resources, interpersonal deficits). Evidence suggests that ACEs affect each of these constructs, and it is likely in the interaction of these constructs with late-life stressors that suicidality in older adulthood emerges. CONCLUSION: ACEs have persistent and multifaceted effects on suicidality in late life. This association is due to multi-varied pathways. It is believed that the explanatory framework developed herein--in which biological, psychological and behavioral factors are organized, and the role of late-life stressors is highlighted--will spark further scientific inquiry into this important area. PMID- 26264209 TI - Experimental Comparison of Efficiency of First Aid Dressings in Burning White Phosphorus on Bacon Model. AB - BACKGROUND: The aim of this study was to determine effectiveness of first aid dressings in extinguishing burning white phosphorous (WP), eliminating WP pieces from the surface, inhibiting re-ignition on the model (fresh bacon covered with military uniform), and preventing from late re-ignition caused by persistent WP pieces. MATERIAL AND METHODS: Burning WP was extinguished with several dressings: tactical Military Dressing (WJ10), wet gauze, 2 hydrocolloids, and 3 prototypes of hydrocolloids developed by the authors. RESULTS: All examined dressings were effective in extinguishing WP provided that the entire area of the burning substance was completely covered. Moist gauze was especially effective in extinguishing WP, and also removed and absorbed the majority of the WP mass, preventing deeper penetration of WP particles. The immediate re-ignition was observed when all the remaining examined dressings were removed from the bacon. A stream of water was dangerous, as it splashed and transferred pieces of WP around. CONCLUSIONS: Moist gauze placed on burning WP for approximately 3 min was most effective in extinguishing WP and removing most of the WP pieces. We recommend moist gauze, used once or twice, as the best primary means for WP elimination and preventing tissue penetration. As a dressing used for medical evacuation (MEDEVAC), or as a second step after complete removal of visible WP, innovative hydrocolloid or hydrogel dressings should be used. PMID- 26264210 TI - Oxygen-responsive genetic circuits constructed in Synechocystis sp. PCC 6803. AB - As photoautotrophic prokaryotes, cyanobacteria are promising platforms for producing value-added bioproducts. However, few regulatory genetic parts and devices (e.g., inducible promoters and regulatory circuits) have been developed for these potential hosts. Furthermore, the devices that have been created respond only to a single input. To address these issues, we developed an inducible genetic circuit that generates heterologous proteins in response to oxygen, an environmental signal. To test its performance and utility in Synechocystis sp. PCC 6803, a model cyanobacterial strain, we connected this circuit to either heterologous nifHDK genes, which encode oxygen-sensitive nitrogenase's structural proteins, or a fluorescent protein gene. The circuit was transcriptionally activated to generate nifHDK transcripts or fluorescent output only in low oxygen conditions. We expanded the oxygen-responsive circuit into a more complex circuit by building a two-input AND gate, which allows Synechocystis to specifically control expression of the fluorescent reporter in response to two signals, low oxygen and high anhydrotetracycline. To our knowledge, the AND gate is the first complex logic circuit built in a cyanobacterial strain. This work expands the synthetic biology tools available for complex gene expression in cyanobacteria, increasing their potential as biotechnology platforms. PMID- 26264212 TI - Foraging behaviour, nutrient intake from pasture and performance of free-range growing pigs in relation to feed CP level in two organic cropping systems. AB - In organic pig production one of the major challenges is to be able to fulfil amino acid requirements based on organic and locally grown protein feed crops. The pig is an opportunistic omnivore with a unique capacity for foraging above and below the soil surface. It is hypothesized that direct foraging in the range area can pose an important contribution in terms of fulfilling nutrient requirements of growing pigs. Foraging activity, lucerne nutrient intake and pig performance were investigated in 36 growing pigs, foraging on lucerne or grass and fed either a standard organic pelleted feed mixture (HP: high protein) or a grain mixture containing 48% less CP (LP: low protein) compared with the high protein feed mixture, from an average live weight of 58 kg to 90 kg in a complete block design in three replicates. The pigs were fed 80% of energy recommendations and had access to 4 m2 of pasture/pig per day during the 40 days experimental period from September to October 2013. Behavioural observations were carried out 12 times over the entire experimental period. For both crops, LP pigs rooted significantly more compared with HP pigs but the effect of CP level was more pronounced in grass (44% v. 19% of all observations) compared with lucerne (28% v. 16% of all observations). Feed protein level turned out not to have any significant effect on grazing behaviour but pigs foraging on lucerne grazed significantly more than pigs foraging on grass (10% v. 4% of all observations). Daily weight gain and feed conversion ratio were significantly affected by feed protein and forage crop interactions. Compared to HP pigs, LP treated pigs had 33% lower daily weight gain (589 v. 878 g) and 31% poorer feed conversion ratio (3.75 v. 2.59 kg feed/kg weight gain) in grass paddocks, whereas in lucerne paddocks LP pigs only had 18% lower daily weight gain (741 v. 900 g) and a 14% poorer feed conversion ratio (2.95 v. 2.54 kg feed/kg weight gain) compared with HP pigs. LP pigs foraging on lucerne used 169 g less concentrate CP/kg weight gain, compared with HP pigs, indicating the nitrogen efficiency of the system. The results indicate that direct foraging of lucerne may be a valuable strategy in terms of accommodating CP and lysine requirements of organic growing pigs. PMID- 26264211 TI - STAT3 polymorphisms may predict an unfavorable response to first-line platinum based therapy for women with advanced serous epithelial ovarian cancer. AB - Cancer stem cells (CSC) contribute to epithelial ovarian cancer (EOC) progression and therapeutic response. We hypothesized that germline single nucleotide polymorphisms (SNPs) in CSC-related genes may predict an initial therapeutic response for women newly diagnosed with EOC. A nested case-control design was used to study 361 women with advanced-stage serous EOC treated with surgery followed by first-line platinum-based combination therapy at Moffitt Cancer Center or as part of The Cancer Genome Atlas Study. "Cases" included 102 incomplete responders (IRs) and "controls" included 259 complete clinical responders (CRs) to therapy. Using Illumina genotyping arrays and imputation, DNA samples were evaluated for 5,509 SNPs in 24 ovarian CSC-related genes. We also evaluated the overall significance of each CSC gene using the admixture maximum likelihood (AML) test, and correlated genotype with EOC tumor tissue expression. The strongest SNP-level associations with an IR to therapy were identified for correlated (r(2) > 0.80) SNPs within signal transducer and activator of transcription 3 (STAT3) [odds ratio (OR), 2.24; 95% confidence interval (CI), 1.32-3.78; p = 0.0027], after adjustment for age, population stratification, grade and residual disease. At the gene level, STAT3 was significantly associated with an IR to therapy (pAML = 0.006). rs1053004, a STAT3 SNP in a putative miRNA binding site, was associated with STAT3 expression (p = 0.057). This is the first study to identify germline STAT3 variants as independent predictors of an unfavorable therapeutic response for EOC patients. Findings suggest that STAT3 genotype may identify high-risk women likely to respond more favorably to novel therapeutic combinations that include STAT3 inhibitors. PMID- 26264213 TI - Effect of anesthesia on gastroesophageal reflux in children: a study using BRAVO wireless pH study measurements. AB - BACKGROUND: Adult studies suggest conscious sedation increases gastroesophageal reflux (GER), but the role of anesthesia on GER in children is unclear. Our aim was to study the anesthesia effects on GER and pH study interpretation in children. METHODS: Children undergoing BRAVO wireless pH capsule placement under anesthesia and study duration >36 h were included. We evaluated the pH parameters (number of reflux episodes >5 min, duration of longest reflux episode, time pH <4 and fraction time pH <4) at 1, 2, 6-h and total study duration blocks using 2 cutoff values (5.3% and 6%) for the worst day, average of both days, and 1st day alone. We compared time blocks to evaluate the effect of anesthesia on GER and the proportions of studies changing interpretation after excluding the 1st hour and 1st 2-h blocks to evaluate anesthesia effect on study interpretation. KEY RESULTS: A total of 150 children were included. We found a significant increase on the pH parameters in the 1st hour compared to subsequent block times suggesting an effect of anesthesia on GER. We found no significant change in the proportion of studies interpreted as normal vs abnormal, however, excluding the initial 2 h of the study would change the study interpretation from abnormal to normal in up to 5% of patients. CONCLUSIONS & INFERENCES: We found an effect of anesthesia increasing the GER parameters mainly in the 1st hour and up to the first 6 h of the study that may result in a change in the study interpretation. PMID- 26264214 TI - Protein Labelling with Versatile Phosphorescent Metal Complexes for Live Cell Luminescence Imaging. AB - To take advantage of the luminescent properties of d(6) transition metal complexes to label proteins, versatile bifunctional ligands were prepared. Ligands that contain a 1,2,3-triazole heterocycle were synthesised using Cu(I) catalysed azide-alkyne cycloaddition "click" chemistry and were used to form phosphorescent Ir(III) and Ru(II) complexes. Their emission properties were readily tuned, by changing either the metal ion or the co-ligands. The complexes were tethered to the metalloprotein transferrin using several conjugation strategies. The Ir(III)/Ru(II)-protein conjugates could be visualised in cancer cells using live cell imaging for extended periods without significant photobleaching. These versatile phosphorescent protein-labelling agents could be widely applied to other proteins and biomolecules and are useful alternatives to conventional organic fluorophores for several applications. PMID- 26264215 TI - Alcohol use disorder severity and reported reasons not to seek treatment: a cross sectional study in European primary care practices. AB - BACKGROUND: Alcohol use disorders are among the mental disorders with the lowest treatment rates. Increasing the treatment rates requires insight on the reasons why patients do not seek treatment. This study examined self-reported reasons for not seeking treatment and their association with alcohol use disorder severity among primary health care patients diagnosed with an alcohol use disorder. METHODS: Alcohol use disorders, health service utilization, and reasons for not seeking treatment were assessed via interviews on regionally representative samples of primary care patients from 6 European countries (Italy, Germany, Hungary, Latvia, Poland and Spain, total N = 9,098). Additionally, general practitioners had to fill in a questionnaire assessing their patients' alcohol use and alcohol use disorders. A multinomial logistic regression was performed to investigate the association between reasons for not seeking treatment and alcohol use disorder severity. RESULTS: Of 1,008 patients diagnosed with an alcohol use disorder (via general practitioner or patient interview) in the past 12 months, the majority (N = 810) did not receive treatment and 251 of those gave a reason for not seeking treatment. The most frequent reason was 'lack of problem awareness' (55.3% of those who responded), the second most common response was 'stigma or shame' (28.6%), followed by 'encounter barriers' (22.8%) and 'cope alone' (20.9%). The results indicated lower probabilities of reporting 'denial' and higher probabilities to report 'encounter barriers' as alcohol use disorders severity increases. However, both trends were discontinued for patients with severe alcohol use disorders. CONCLUSIONS: Particularly at lower levels of alcohol use disorder severity, a lack of problem awareness prevents patients from seeking treatment. Routinely alcohol consumption monitoring in primary care practices could help primary and secondary prevention of alcohol use disorders and increase treatment coverage. PMID- 26264217 TI - Nurses' perceptions of their professional practice environment: a cross-sectional study. AB - AIMS AND OBJECTIVES: To describe nurses' perceptions concerning their professional practice environment in mainland China and identify factors associated with these views. BACKGROUND: Globally, the environments in which nurses work influence the quality of nursing practice and health care. DESIGN: A cross-sectional descriptive survey using both paper- and online-based delivery modes was used. METHOD: A convenience sampling method was used. The survey questionnaire was composed of sociodemographic items and the 38-item Chinese version of Professional Practice Environment survey. The content of the paper based questionnaire was identical to the online survey. Pearson's chi-square test was conducted to compare the demographic characteristics of these two data sets. Descriptive statistics analysis included frequency, percentage, mean and standard deviation. Multiple linear regression analysis using the Backwards method was applied to identify independent predictors of each subscale of the 38-item Chinese version of Professional Practice Environment. RESULTS: A total of 573 questionnaires were analysed. The mean score of each subscale of the 38-item Chinese version of Professional Practice Environment in this study ranged from 2.66-3.05. All subscales except work motivation (3.05, standard deviation: 0.44) scored less than 3.0. Areas rated as most in need of improvement included control over practice, interpersonal interaction, supportive leadership and handling conflict, and staff relationships with physicians and autonomy. CONCLUSION: This study has identified nurses' perspectives regarding their workplaces in contemporary China. These data have provided an important baseline for developing and implementing culturally appropriate strategies to improve the working environment of Chinese nurses. RELEVANCE TO CLINICAL PRACTICE: A supportive and enabling work environment promotes professional development and the safety and quality of health care. Addressing these factors is important in optimising work place environments. PMID- 26264216 TI - Review article: biomarkers and personalised therapy in functional lower gastrointestinal disorders. AB - BACKGROUND: Treatment of IBS and functional lower gastrointestinal disorders is still based predominantly on symptoms; biomarkers that reflect the mechanism or pathophysiology have been identified. Given the diverse mechanisms that result in the same clinical phenotype of IBS, it is hypothesised that identification of biomarkers may lead to individualisation of medical therapy. AIM: To review the biomarkers that have been appraised in IBS. METHODS: A single author reviewed the published literature on biomarkers appraised in IBS. RESULTS: The current literature suggests that these biomarkers are insufficiently sensitive or specific to differentiate IBS from health or from other diseases causing similar symptoms, such as coeliac disease or inflammatory bowel disease. Most of the proposed biomarkers are not actionable, that is, they do not lead to an efficacious therapy based on the biological inference of the biomarker itself. However, among proposed biomarkers in IBS, some are actionable, as they specifically reflect a quantitative difference in a mediator of dysfunction or result in a quantifiable disturbance of function that can be specifically treated. Such biomarkers may potentially identify relevant subgroups that respond to specific therapy. The most promising actionable biomarkers are measurement of colonic transit (leading to treatments that reverse the abnormal transit) and measurements of bile acid diarrhoea to identify responders to bile acid sequestrants. CONCLUSIONS: Therefore, although biomarkers are not ready for prime time as diagnostic tests in IBS, some biomarkers could identify subgroups of patients with IBS for inclusion in clinical trials that target specific dysfunctions. Such an approach may enhance treatment efficacy, and may ultimately help reduce costs in drug development and in the management of patients in clinical practice. PMID- 26264218 TI - Postmortem Intervals in Mice Submerged in Aqueous Environments at 20 degrees C. AB - Aqueous submersion can impede decay and produce decomposition stages not seen in terrestrial burials. To further understand the variances, fifty-four mice were submerged in freshwater, marine water, and a control environment at 20 degrees C. The mice displayed sequential stages at differing rates over 6 weeks. Regression plots and comparative t-tests demonstrated that internal putrefaction, weight difference, and abdominal circumference of the aqueous environments varied significantly from the control group. The aqueous subjects did not vary significantly from each other quantitatively. The postmortem intervals were not consistent regardless of temperature or environment although a clear variance was noted between the control and the submerged groups. PMID- 26264219 TI - Obliterative portal venopathy without portal hypertension: an underestimated condition. AB - BACKGROUND & AIMS: Obliterative portal venopathy without portal hypertension has been described by a single study in a limited number of patients, thus very little is known about this clinical condition. This study aimed to investigate the prevalence of obliterative portal venopathy and its clinical-pathological correlations in patients with cryptogenic chronic liver test abnormalities without clinical signs of portal hypertension. METHODS: We analysed 482 liver biopsies from adults with non-cirrhotic cryptogenic chronic liver disorders and without any clinical signs of portal hypertension, consecutively enrolled in a 5 year period. Twenty cases of idiopathic non-cirrhotic portal hypertension diagnosed in the same period, were included for comparison. Histological findings were matched with clinical and laboratory features. RESULTS: Obliterative portal venopathy was identified in 94 (19.5%) of 482 subjects and in all 20 cases of idiopathic non-cirrhotic portal hypertension: both groups shared the entire spectrum of histological changes described in the latter condition. The prevalence of incomplete fibrous septa and nodular regenerative hyperplasia was higher in the biopsies of idiopathic non-cirrhotic portal hypertension (P = 0.006 and P = 0.002), a possible hint of a more advanced stage of the disease. The two groups also shared several clinical laboratory features, including a similar liver function test profile, concomitant prothrombotic conditions and extrahepatic autoimmune disorders. CONCLUSION: Obliterative portal venopathy occurs in a substantial proportion of patients with unexplained chronic abnormal liver function tests without portal hypertension. The clinical-pathological profile of these subjects suggests that they may be in an early (non-symptomatic) stage of idiopathic non-cirrhotic portal hypertension. PMID- 26264220 TI - High-resolution ultrasound of peripheral nerves in systemic sclerosis: a pilot study of computer-aided quantitative assessment of nerve density. AB - OBJECTIVES: To quantitatively evaluate and compare nerve density in patients with limited cutaneous systemic sclerosis (lcSSc) and control subjects using high resolution ultrasound (US) with a computer-aided assessment. METHODS: Forty patients and 40 age- and sex-matched control subjects were prospectively enrolled. Ultrasound (US) examination (17-5 MHz probe) of the median nerve at the elbow was performed bilaterally by one radiologist. A software quantified the ratio between the hypoechoic and hyperechoic areas of peripheral nerves on ultrasound. Two observers set the threshold in the images acquired, and three observers performed the digital analysis of nerve density. Statistical analysis included Mann-Whitney U-test of patients versus control subjects and subgroup analysis of symptomatic and non-symptomatic patients. Intra and inter-observer agreement of the three observers were assessed with the kappa statistic. RESULTS: In all, 160 median nerves were evaluated. According to the US, nerve density was significantly reduced in lcSSc patients compared to control subjects (mean and standard deviation: 41 +/- 3 vs 56 +/- 4, p < 0.01). Subgroup analysis showed that symptomatic patients (n = 15) had reduced nerve density compared to non symptomatic (n = 25) patients (39 +/- 5 vs 43 +/- 4, p < 0.01). Intra-observer agreement was very good (K = 0.82). Inter-observer agreements were good: reader 1 vs reader 2: k = 0.78 (95% confidence interval 0.65 to 0.91); reader 2 vs reader 3: k = 0.72 (95% confidence interval 0.65 to 0.82); reader 3 vs reader 1: k = 0.71 (95% confidence interval 0.64-0.81). CONCLUSIONS: In lcSSc patients, nerve density was reduced, especially in the symptomatic group, compared to control subjects. PMID- 26264221 TI - A DFT Study of Tungsten-Methylidene Formation on a W/ZSM-5 Zeolite: The Metathesis Active Site. AB - Tungsten-methylidene formation from ethene on either the W(IV) , W(V) , or W(VI) active sites of a W/ZSM-5 zeolite is investigated by using the M06-L functional. The reaction is assumed to proceed in two steps; the first step is the [2+2] cycloaddition between ethene and the W-O active site to form an oxametallacycle intermediate. The intermediate is then decomposed to produce the W-methylidene active site from the metathesis reaction. The overall activation barrier of the reaction on W(VI) (27.3 kcal mol(-1) ) is considerably lower than the ones for W(IV) and W(V) (69.4 and 37.1 kcal mol(-1) , respectively). Moreover, the reaction involving the W(VI) site also stabilizes intermediates and products to a larger extent than the ones on the W(IV) and W(V) sites. As a result, we have demonstrated that the reaction of the W-methylidene metathesis active site is both kinetically and thermodynamically favored to occur on the W(VI) active site of the zeolite. PMID- 26264223 TI - Can hepatic resection provide a long-term cure for patients with intrahepatic cholangiocarcinoma? AB - BACKGROUND: A patient can be considered statistically cured from a specific disease when their mortality rate returns to the same level as that of the general population. In the current study, the authors sought to assess the probability of being statistically cured from intrahepatic cholangiocarcinoma (ICC) by hepatic resection. METHODS: A total of 584 patients who underwent surgery with curative intent for ICC between 1990 and 2013 at 1 of 12 participating institutions were identified. A nonmixture cure model was adopted to compare mortality after hepatic resection with the mortality expected for the general population matched by sex and age. RESULTS: The median, 1-year, 3-year, and 5-year disease-free survival was 10 months, 44%, 18%, and 11%, respectively; the corresponding overall survival was 27 months, 75%, 37%, and 22%, respectively. The probability of being cured of ICC was 9.7% (95% confidence interval, 6.1%-13.4%). The mortality of patients undergoing surgery for ICC was higher than that of the general population until year 10, at which time patients alive without tumor recurrence can be considered cured with 99% certainty. Multivariate analysis demonstrated that cure probabilities ranged from 25.8% (time to cure, 9.8 years) in patients with a single, well-differentiated ICC measuring <=5 cm that was without vascular/periductal invasion and lymph nodes metastases versus <0.1% (time to cure, 12.6 years) among patients with all 6 of these risk factors. A model with which to calculate cure fraction and time to cure was developed. CONCLUSIONS: The cure model indicated that statistical cure was possible in patients undergoing hepatic resection for ICC. The overall probability of cure was approximately 10% and varied based on several tumor specific factors. Cancer 2015;121:3998-4006. (c) 2015 American Cancer Society. PMID- 26264222 TI - FoxM1 transactivates PTTG1 and promotes colorectal cancer cell migration and invasion. AB - BACKGROUND: Metastasis is the major cause of cancer-related death. Forkhead Box M1 (FoxM1) is a master regulator of tumor metastasis. This study aims to identify new FoxM1 targets in regulating tumor metastasis using bioinformatics tools as well as biological experiments. METHODS: Illumina microarray was used to profile WT and PTTG1 knockout HCT116 cells. R2 Genomics Analysis was used to identify PTTG1 as a potential FoxM1 targeted gene. Luciferase reporter array, EMSA and Chromatin Immunoprecipitation (ChIP) were used to determine the binding of FoxM1 to PTTG1 promoter. Boyden chamber assay was used to evaluate the effects of FoxM1 PTTG1 on cell migration and invasion. Splenic-injection induced liver metastasis model was used to evaluate the effects of FoxM1-PTTG1 on liver metastasis of colorectal cancer. RESULTS: Analyses of multiple microarray datasets derived from human colorectal cancer indicated that correlation levels of FoxM1 and pituitary tumor transforming gene (PTTG1) are highly concordant (R = 0.68 ~ 0.89, p = 2.1E 226 ~ 9.6E-86). FoxM1 over-expression increased and knock-down decreased PTTG1 expression. Luciferase reporter assay identified that the -600 to -300 bp region of PTTG1 promoter is important for FoxM1 to enhance PTTG1 promoter activity. EMSA and ChIP assays confirmed that FoxM1 directly binds to PTTG1 promoter at the -391 to -385 bp region in colorectal cancer cells. Boyden chamber assay indicated that both FoxM1 and PTTG1 regulate migration and invasion of HCT116 and SW620 colorectal cancer cells. Further in vivo assays indicated that PTTG1 knock out decreased the liver metastasis of FoxM1 over-expressing HCT116 cells. Microarray analyses identified 662 genes (FDR < 0.05) differentially expressed between WT and PTTG1(-/-) HCT116 cells. Among them, dickkopf homolog 1 (DKK1), a known WNT pathway inhibitor, was suppressed by PTTG1 and FoxM1. CONCLUSIONS: PTTG1 is a FoxM1 targeted gene. FoxM1 binds to PTTG1 promoter to enhance PTTG1 transcription, and FoxM1-PTTG1 pathway promotes colorectal cancer migration and invasion. PMID- 26264224 TI - Colorectal cancer risk factors in patients with serrated polyposis syndrome: a large multicentre study. AB - OBJECTIVE: Serrated polyposis syndrome (SPS) is associated with an increased colorectal cancer (CRC) risk, although the magnitude of the risk remains uncertain. Whereas intensive endoscopic surveillance for CRC prevention is advised, predictors that identify patients who have high CRC risk remain unknown. We performed a multicentre nationwide study aimed at describing the CRC risk in patients with SPS and identifying clinicopathological predictors independently associated with CRC. DESIGN: From March 2013 through September 2014, patients with SPS were retrospectively recruited at 18 Spanish centres. Data were collected from medical, endoscopy and histopathology reports. Multivariate logistic regression was performed to identify CRC risk factors. RESULTS: In 296 patients with SPS with a median follow-up time of 45 months (IQR 26-79.7), a median of 26 (IQR 18.2-40.7) serrated polyps and 3 (IQR 1-6) adenomas per patient were detected. Forty-seven patients (15.8%) developed CRC at a mean age of 53.9+/ 12.8, and 4 out of 47 (8.5%) tumours were detected during surveillance (cumulative CRC incidence 1.9%). Patients with >2 sessile serrated adenomas/polyps (SSA/Ps) proximal to splenic flexure and >=1 proximal SSA/P with high-grade dysplasia were independent CRC risk factors (incremental OR=2, 95% CI 1.22 to 3.24, p=0.006). Patients with no risk factors showed a 55% decrease in CRC risk (OR=0.45, 95% CI 0.24 to 0.86, p=0.01). CONCLUSIONS: Patients with SPS have an increased risk of CRC, although lower than previously published. Close colonoscopy surveillance in experienced centres show a low risk of developing CRC (1.9% in 5 years). Specific polyp features (SSA/P histology, proximal location and presence of high-grade dysplasia) should be used to guide clinical management. PMID- 26264225 TI - Role of macrophage secretions on rat polycystic ovary: its effect on apoptosis. AB - Polycystic ovarian syndrome is the most common endocrine disorder among women of reproductive age. Little is known about its etiology, although the evidence suggests an intrinsic ovarian abnormality in which endocrine, metabolic, neural and immune factors would be involved. In this work, the effects of macrophage (MO) secretion on ovarian apoptosis in a polycystic ovary syndrome rat model (PCO rat) induced by estradiol valerate are studied. Spleen MO secretions were used to stimulate ovaries and ovarian interstitial and granulosa cells from both PCO and control rats. Ovarian hormones and prostaglandin E2 (PGE2) were measured by RIA; ovarian mRNA levels of Bax, Bcl2 and NFkB by RT-PCR; and ovarian inducible nitric oxide synthase (iNOS) by western blot. The number of apoptotic cells was evaluated by TUNEL. In the PCO ovary, the MO secretions from PCO rats increased the Bax and NFkB mRNA expressions and increased TUNEL staining in both granulosa and theca cells. In addition, the PCO MO secretions produced a decrease of nitric oxide release, iNOS protein level and PGE2 content in the PCO ovary, and it also induced an increase of androstenedione production by PCO interstitial cells, in comparison with control MO secretions. Considering these results and knowing that testosterone stimulates tumour necrosis factor-alpha production by PCO MO modifying ovarian response by increasing androstenedione, it is reasonable to suggest that the increase of androgens stimulated in ovarian cells by PCO MO secretions could in turn stimulate the cytokine production from MO, thus maintaining an apoptotic vicious cycle in the PCO ovary. PMID- 26264226 TI - Close the loop to show patients the value of taking part in research. PMID- 26264227 TI - Installation of speed humps and pedestrian-motor vehicle collisions in Toronto, Canada: a quasi-experimental study. AB - BACKGROUND: Evidence related to the effectiveness of speed humps on reducing pedestrian-motor vehicle collisions (PMVC) has been conflicting. The purpose of this study was to determine the association between speed hump installation and changes in PMVC rates in Toronto, Canada. METHODS: Speed humps were mapped along with police-reported pedestrian collisions from 2000-2011 and built environment roadway characteristics. A quasi-experimental study identified collision counts before and after speed hump installation, modeled using repeated measures Poisson regression adjusted for season and roadway characteristics. Stratified analyses were conducted by age group and injury severity. RESULTS: There were 27,827 PMVC, with 1344 collisions along 409 roadways with speed humps. PMVC incidence rates/meters of road/month decreased after installation of speed humps (IRR 0.78 95 % CI 0.66, 0.91). Winter, collector roads (versus local), pre-amalgamated city centre and increased land use mix were associated with more collisions. The association between speed humps and PMVC rates decreased more for children (IRR 0.57, 95 % CI 0.41, 0.79) than for adults (IRR 0.80, 95 % CI 0.68, 0.95). CONCLUSIONS: Speed humps are an easily replicated method of traffic calming which have a significant protective effect on PMVC on the roadways where they are installed, particularly for children. There is a need for an area-wide analysis to determine the effects of the installation of speed humps to ensure that PMVC are not being displaced to surrounding roadways. PMID- 26264228 TI - Oesophagectomy in a patient with azygos vein continuation of the inferior vena cava: report of a case. AB - The azygos system of veins varies greatly in its mode of origin, but the variation in which the azygos vein is a continuation of the inferior vena cava (IVC) is rare. During an oesophagectomy, the azygos vein typically is transected as a requirement of the surgery. In this case, the enlarged azygos and its arch were a continuation of the IVC. During our procedure, we first established a bypass between the right femoral vein and the jugular vein in case of injury to the azygos vein, and we then performed a McKeown oesophagectomy without transecting the azygos vein. Our experience suggests that an oesophagectomy in cases with an azygos vein continuation of the IVC is feasible. An adequate medical examination and careful reading of the imaging is crucial for the safety of these surgical procedures. An appropriate surgical approach should be selected according to the location of the tumour, the size of the tumour and its anatomical features. The establishment of a veno-venous bypass and protection of the azygos arch in patients whose azygos vein is a continuation of IVC is necessary. PMID- 26264229 TI - Knudson's hypothesis revisited in Indian retinoblastoma patients. AB - AIM: Retinoblastoma (RB) is the most common primary intraocular malignancy affecting children under 5 years of age. This study aims to correlate the clinical parameters with RB1 mutation in the light of Knudson's two-hit hypothesis in Indian RB patients. METHODS: We analyzed the clinical details of 73 RB patients visiting Aravind Eye Hospital, Madurai, India, between January and October 2012. Data on gender, presenting age and sign, laterality, number of tumors in each eye and family history were collected. A semi log plot was derived based on Knudson's two-hit hypothesis. Genetic analysis of RB1 was carried out to identify the two hits. RESULTS: The mean age at diagnosis for unilateral and bilateral cases was 24.0 +/- 15.1 and 9.8 +/- 11.5 months, respectively. Familial RB was seen in 13 (17.8%) patients of whom 11 were bilateral. Multiple tumors were observed more frequently in bilateral than in unilateral cases. All unilateral and bilateral patients followed the two-hit and one-hit curves, respectively, confirming Knudson's hypothesis in Indian patients. Genetic analysis identified two somatic mutations in tumor samples of sporadic unilateral cases. Among the two bilateral patients, one received the first hit from her father and the other patient developed a de novo germline mutation during early development. CONCLUSION: The two-hit hypothesis has been reestablished in Indian patients. Genetic analysis of tumor samples has also complemented the statistical analysis to reaffirm the two hits in tumor development. PMID- 26264230 TI - In vitro efficacy of allicin on chicken Eimeria tenella sporozoites. AB - Chicken coccidiosis is a major parasitic disease caused by Eimeria spp. It is controlled and treated using chemical anticoccidial agents. Development of partial or complete resistance toward these anticoccidials is considered a major problem in poultry industry. Allicin is an organosulfur compound produced as a result of the reaction between alliin and alliinase after hacking of garlic. In this study, tenfold dilution from 180 mg/ml to 1.8 ng/ml of allicin in distilled water was tested against E. tenella in vitro. The percent of inhibition in allicin was from 99.9 to 71.53% using 180 mg/ml and 180 ng/ml, respectively. The percent of inhibition was 56.24% using 1.8 ng/ml. We used allicin as a treatment from plants against chicken coccidiosis; however, in vivo study should be performed to confirm these results. PMID- 26264231 TI - Abnormalities in the WFU strain of Taenia crassiceps (Cyclophyllidea: Taeniidae) following years of propagation in mice. AB - Asexually proliferating Taenia crassiceps (Zeder, 1800) metacestodes isolated within past decades have been successfully sub-cultured under experimental conditions using Mus musculus Linnaeus, 1758 mice. However, during their development, morphological irregularities of scolex structures have been reported in two of the three strains of this cestode species maintained in mice - ORF and KBS. The main goal of this work is to describe the abnormalities observed in a sample of 118 cysticerci of the third T. crassiceps strain used at present - WFU. Morphological abnormalities were detected in 39.8% of the evaginated scoleces; they consisted of supernumerary suckers (n= 2), duplicated (n= 2) or absent rostellum (n= 1), as well as absent or aberrant (n= 29) hooks, which were significantly shorter when compared to the large and short hook lengths referred to in the literature. PMID- 26264233 TI - Once-daily prolonged release tacrolimus in liver transplantation: Experts' literature review and recommendations. AB - The efficacy and safety of tacrolimus (Tac) twice daily (bid) and once a day (qd) formulations are considered to be similar. However, the available information regarding initiation of Tac qd is sparse, and practical information is lacking. On the basis of a literature review, clinical efficacy, and safety trials, French experts in the liver transplantation field were asked to highlight pharmacokinetic (PK) differences between both formulations to assess efficacy and safety of the qd formulation in the context of de novo initiation or conversion and to provide their recommendations for initiation and day-to-day management of Tac qd. The same efficacy and safety profile is found for both immediate-release and prolonged-release Tac. PK differences carry on absorption because of the difference in formulations but not on metabolism or excretion. Tac qd offers a better reproducibility in exposure than Tac bid but is associated with an increased risk of disturbed absorption in case of a change in intestinal motility. The same therapeutic drug monitoring with Tac qd and bid could be applied, based on minimal concentration (trough level; C(min)), as there is a similar strong correlation between C(min) and the area under the curve (AUC) for both formulations. Different protocols for Tac qd initiation were described through numerous studies, except for early conversion: initiation on day 0, using 0.10 to 0.20 mg/kg/day as monotherapy, or lower dosages in case of concomitant immunosuppressant treatment or poor graft quality; early conversion from day 5 to 6 months, preferably before hospital discharge, using a 1 to 1.3 mg/kg/day schedule and with first C(min) assessment 48 hours after the conversion; and later conversion (>6 months posttransplantation) using a milligram-to-milligram dosage schedule, and with dose adjustment based on weekly C(min) measurement. Experts underline that an increase in treatment adherence was expected using Tac qd in liver recipients. In conclusion, Tac qd has the same efficacy and safety profile as Tac bid. De novo introduction or later conversion are well documented but could differ from day-to-day practice. PMID- 26264232 TI - WAC loss-of-function mutations cause a recognisable syndrome characterised by dysmorphic features, developmental delay and hypotonia and recapitulate 10p11.23 microdeletion syndrome. AB - BACKGROUND: Rare de novo mutations have been implicated as a significant cause of idiopathic intellectual disability. Large deletions encompassing 10p11.23 have been implicated in developmental delay, behavioural abnormalities and dysmorphic features, but the genotype-phenotype correlation was not delineated. Mutations in WAC have been recently reported in large screening cohorts of patients with intellectual disability or autism, but no full phenotypic characterisation was described. METHODS: Clinical and molecular characterisation of six patients with loss-of-function WAC mutations identified by whole exome sequencing was performed. Clinical data were obtained by retrospective chart review, parental interviews, direct patient interaction and formal neuropsychological evaluation. RESULTS: Five heterozygous de novo WAC mutations were identified in six patients. Three of the mutations were nonsense, and two were frameshift; all are predicted to cause loss of function either through nonsense-mediated mRNA decay or protein truncation. Clinical findings included developmental delay (6/6), hypotonia (6/6), behavioural problems (5/6), eye abnormalities (5/6), constipation (5/6), feeding difficulties (4/6), seizures (2/6) and sleep problems (2/6). All patients exhibited common dysmorphic features, including broad/prominent forehead, synophrys and/or bushy eyebrows, depressed nasal bridge and bulbous nasal tip. Posteriorly rotated ears, hirsutism, deep-set eyes, thin upper lip, inverted nipples, hearing loss and branchial cleft anomalies were also noted. CONCLUSIONS: Our case series show that loss-of-function mutations in WAC cause a recognisable genetic syndrome characterised by a neurocognitive phenotype and facial dysmorphism. Our data highly suggest that WAC haploinsufficiency is responsible for most of the phenotypic features associated with deletions encompassing 10p11.23. PMID- 26264234 TI - An Arabidopsis mutant of inositol pentakisphosphate 2-kinase AtIPK1 displays reduced arsenate tolerance. AB - Arsenate [As(V)] toxicity is considered to be derived from similarities in the chemical properties of As(V) and phosphate (Pi). An Arabidopsis thaliana mutant of inositol pentakisphosphate 2-kinase (AtIPK1), atipk1-1, has previously exhibited lower level of phytate and higher level of Pi, relative to wild-type (WT). Here, atipk1-1 displayed hypersensitivity to As(V) stress and less As(V) uptake when compared to WT. Overexpression of AtIPK1 controlled by the CaMV 35S promoter partially rescued the As(V)-sensitive phenotype of atipk1-1. When compared to control Pi status, addition of Pi enhanced As(V) tolerance of both WT and atipk1-1 plants, while the arsenic concentration was less reduced in the latter genotype. Despite the higher Pi level in atipk1-1 than did WT plants, the mutant suffered more severe Pi starvation under Pi limitation stress, indicating that Pi homeostasis was altered in the mutant. Gene expression analysis of WT and atipk1-1 plants showed the diverse effect of As(V) stress on Pi starvation dependent regulation of Pi-responsive genes. Our study suggested that a particular mechanism of As(V) toxicity existed in atipk1-1 mutant, and may offer new insights into the interactions between Pi homeostasis and As(V) detoxification in plants. PMID- 26264235 TI - Geographic Disparities in Access to Agencies Providing Income-Related Social Services. AB - Geographic location is an important factor in understanding disparities in access to health-care and social services. The objective of this cross-sectional study is to evaluate disparities in the geographic distribution of income-related social service agencies relative to populations in need within Boston. Agency locations were obtained from a comprehensive database of social services in Boston. Geographic information systems mapped the spatial relationship of the agencies to the population using point density estimation and was compared to census population data. A multivariate logistic regression was conducted to evaluate factors associated with categories of income-related agency density. Median agency density within census block groups ranged from 0 to 8 agencies per square mile per 100 population below the federal poverty level (FPL). Thirty percent (n = 31,810) of persons living below the FPL have no access to income related social services within 0.5 miles, and 77 % of persons living below FPL (n = 83,022) have access to 2 or fewer agencies. 27.0 % of Blacks, 30.1 % of Hispanics, and 41.0 % of non-Hispanic Whites with incomes below FPL have zero access. In conclusion, some neighborhoods in Boston with a high concentration of low-income populations have limited access to income-related social service agencies. PMID- 26264236 TI - [Immunological memory of the bone marrow]. PMID- 26264237 TI - Pleomorphic dermal sarcoma: a more aggressive neoplasm than previously estimated. AB - BACKGROUND: Pleomorphic dermal sarcoma (PDS) is a rare neoplasm sharing pathological features with atypical fibroxanthoma, but adding tumor necrosis, invasion beyond superficial subcutis or vascular or perineural infiltration. Although its metastatic risk has been estimated to be less than 5%, its real outcome is presently uncertain because of its rarity and to the lack of homogeneous criteria used in reported cases. METHODS: Retrospective clinicopathological study of 18 cases of PDS. RESULTS: The lesions presented as tumors or plaques (size: 7-70 mm) on the head of elderly patients (median: 81 years), without a gender predominance. Histopathologically, they consisted of spindle cells arranged in a fascicular pattern, containing pleomorphic epithelioid and giant multinucleated cells in varying proportions, and usually exhibiting numerous mitotic figures and infiltrative tumor margins. No immunoexpression for cytokeratins, S100 protein, desmin or CD34 was observed. Necrosis and venous invasion were found in three tumors each (17%). Follow-up was available in 15 cases (median: 33 months). Three patients (20%) had local recurrences, all with incomplete primary surgical resections. Three patients (20%) developed distant metastases in the skin, regional lymph nodes and/or lungs and died from the disease. CONCLUSION: Our data suggest that PDS may be a more aggressive neoplasm than previously estimated. PMID- 26264238 TI - Influence of rhizobacterial volatiles on the root system architecture and the production and allocation of biomass in the model grass Brachypodium distachyon (L.) P. Beauv. AB - BACKGROUND: Plant growth-promoting rhizobacteria are increasingly being seen as a way of complementing conventional inputs in agricultural systems. The effects on their host plants are diverse and include volatile-mediated growth enhancement. This study sought to assess the effects of bacterial volatiles on the biomass production and root system architecture of the model grass Brachypodium distachyon (L.) Beauv. RESULTS: An in vitro experiment allowing plant-bacteria interaction throughout the gaseous phase without any physical contact was used to screen 19 bacterial strains for their growth-promotion ability over a 10-day co cultivation period. Five groups of bacteria were defined and characterised based on their combined influence on biomass production and root system architecture. The observed effects ranged from unchanged to greatly increased biomass production coupled with increased root length and branching. Primary root length was increased only by the volatile compounds emitted by Enterobacter cloacae JM22 and Bacillus pumilus T4. Overall, the most significant results were obtained with Bacillus subtilis GB03, which induced an 81 % increase in total biomass, as well as enhancing total root length, total secondary root length and total adventitious root length by 88.5, 201.5 and 474.5 %, respectively. CONCLUSIONS: This study is the first report on bacterial volatile-mediated growth promotion of a grass plant. Contrasting modulations of biomass production coupled with changes in root system architecture were observed. Most of the strains that increased total plant biomass also modulated adventitious root growth. Under our screening conditions, total biomass production was strongly correlated with the length and branching of the root system components, except for primary root length. An analysis of the emission kinetics of the bacterial volatile compounds is being undertaken and should lead to the identification of the compounds responsible for the observed growth-promotion effects. Within the context of the inherent characteristics of our in vitro system, this paper identifies the next critical experimental steps and discusses them from both a fundamental and an applied perspective. PMID- 26264239 TI - Breastfeeding modifies the effects of environment tobacco smoke exposure on respiratory diseases and symptoms in Chinese children: the Seven Northeast Cities Study. AB - To evaluate the potential effect of interaction between breastfeeding and environmental tobacco smoke (ETS) exposure on respiratory health, we studied 31 049 children (aged 2-14 years) from 25 districts of seven cities in northeast China. Parents of the children completed standardized questionnaires that characterized the children's histories of respiratory symptoms and illness, feeding methods, ETS exposure, and other associated risk factors. Breastfeeding was defined as having been mainly breastfed for 3 months or more. The results showed that the association of ETS exposure with childhood respiratory conditions/diseases was modified by breastfeeding, and the association for nonbreastfed children was stronger than that for breastfed children. In particular, for nonbreastfed children, the odds ratios (ORs) for the effect of current ETS exposure asthma was 1.71 (95% CI: 1.43-2.05); however, the OR for breastfed children was 1.33 (95% CI: 1.20-1.48), indicating that the interactions between breastfeeding and current ETS exposure on asthma were statistically significant (P = 0.019). When stratified by school (kindergarten vs. elementary school), breastfeeding was more protective for asthma-related symptoms among children from kindergarten. In conclusion, this study shows that breastfeeding is associated with smaller associations between ETS exposure and respiratory conditions in children, suggesting that breastfeeding reduces susceptibility to the respiratory effects of ETS. PMID- 26264240 TI - Chronic Alcohol Exposure Decreases 53BP1 Protein Levels Leading to a Defective DNA Repair in Cultured Primary Cortical Neurons. AB - Chronic alcohol consumption may cause neurodevelopmental and neurodegenerative disorders. Alcohol neurotoxicity is associated with the production of acetaldehyde and reactive oxygen species that induce oxidative DNA damage. However, the molecular mechanisms by which ethanol disturbs the DNA damage response (DDR), resulting in a defective DNA repair, remain unknown. Here, we have used cultured primary cortical neurons exposed to 50 or 100 mM ethanol for 7 days to analyze the ethanol-induced DDR. Ethanol exposure produced a dose dependent generation of double strand breaks and the formation of DNA damage foci immunoreactive for the histone gammaH2AX, a DNA damage marker, and for the ubiquitylated H2A, which is involved in chromatin remodeling at DNA damage sites. Importantly, these DNA damage foci failed to recruit the protein 53BP1, a crucial DNA repair factor. This effect was associated with a drop in 53BP1 mRNA and protein levels and with an inhibition of global transcription. Moreover, ethanol exposed neurons treated with ionizing radiation (2 Gy) also failed to recruit 53BP1 at DNA damage foci and exhibited a greater vulnerability to DNA lesions than irradiated control neurons. Our results support that defective DNA repair, mediated by the deficient expression and recruitment of 53BP1 to DNA damage sites, represents a novel mechanism involved in ethanol neurotoxicity. The design of therapeutic strategies that increase or stabilize 53BP1 levels might potentially promote DNA repair and partially compensate alcohol neurotoxicity. PMID- 26264241 TI - Structural elucidation of some antimicrobial constituents from the leaf latex of Aloe trigonantha L.C. Leach. AB - BACKGROUND: The incidents of drug resistant microorganisms and the need of treatments for newly emerging pathogens are of great concern to the global community. Our ability to treat infectious diseases is dependent on the development of new pharmaceuticals, and one potential source being medicinal plants with traditional claims. The leaves of Aloe trigonantha L.C. Leach, an endemic Ethiopian plant, are locally used for the treatment of infectious and inflammatory diseases. This study explores the potential of the latex of this plant and compounds isolated thereof for their in vitro antibacterial and antifungal properties. METHODS: Analytical RP-HPLC and silica gel preparative TLC were used for identification and isolation of active constituents, respectively. Characterization of the compounds was based on UV, IR, HR-ESIMS, (1)H and (13)C NMR, and 2D-NMR spectral assignments. Antimicrobial activity studies were carried out against 21 pathogenic bacterial and 4 fungal strains using the disk diffusion method. Minimum inhibitory concentrations (MICs) were determined by the broth dilution method. RESULTS: A C-glycosylated chromone identified as aloesin, and three C-glycosylated anthrones characterized as 8-O-methy-7-hydroxyaloin A/B, aloin A/B and aloin-6'-O-acetate A/B were isolated. The latex and isolated compounds exhibited in vitro antibacterial activity against the tested pathogens. In some cases the activity of the isolated compounds (MIC = 10 MUg/mL) was comparable with that of the standard drug ciprofloxacin, particularly against some of the Gram-negative bacterial strains tested. However, their activity towards the fungal pathogens tested was relatively weaker showing maximum activity against Candida albicans with MIC value of 400 MUg/mL. CONCLUSION: The present findings can be used for further research aimed at the development of new antibacterial agents, and may also justify the ethnomedicinal claim of the plant for the treatment of infectious diseases. PMID- 26264242 TI - Retinoblastoma-binding protein 2 induces epithelial-mesenchymal transition in esophageal squamous cancer cells. AB - OBJECTIVES: To investigate the effect of retinoblastoma-binding protein 2 (RBP2) on epithelial-mesenchymal transition (EMT) in esophageal squamous cancer cells and to compare the effect of RBP2 in lung squamous cancer cells and esophageal squamous cancer cells. RESULTS: When transfected with RBP2 siRNA, the migrated cells were 36.3 +/- 6.03 by transwell migration assay, compared to 107 +/- 6.7 cells in the control group. The mRNA level of epithelial cadherin (E-cadherin) was 1.54 +/- 0.14 times higher than in the control group, and that of neural cadherin (N-cadherin) fell to 0.76 +/- 0.03 times. The relative luciferase activity of E-cadherin promoter rose to 3.84 +/- 0.23 times. Correspondingly, the expression of E-cadherin protein increased and that of N-cadherin protein decreased. When SK-MES-1 cells were transfected with RBP2 siRNA, their relative mRNA level of E-cadherin was 8.6 +/- 0.37 times as high as that in control group, which was higher than that in Eca-109 cells. The E-cadherin protein was also greater in SK-MES-1 cells. CONCLUSION: RBP2 could induce EMT in esophageal cancer cells and exert a greater effect on the expression of E-cadherin in lung squamous cells than in esophageal squamous cells. PMID- 26264243 TI - Reductive dehalogenation of 3,5-dibromo-4-hydroxybenzoate by an aerobic strain of Delftia sp. EOB-17. AB - OBJECTIVES: To confirm the reductive dehalogenation ability of the aerobic strain of Delftia sp. EOB-17, finding more evidences to support the hypothesis that reductive dehalogenation may occur extensively in aerobic bacteria. RESULTS: Delftia sp. EOB-17, isolated from terrestrial soil contaminated with halogenated aromatic compounds, completely degraded 0.2 mM DBHB in 28 h and released two equivalents of bromides under aerobic conditions in the presence of sodium succinate. LC-MS analysis revealed that DBHB was transformed to 4-hydroxybenzoate via 3-bromo-4-hydroxybenzoate by successive reductive dehalogenation. Highly conserved DBHB-degrading genes, including reductive dehalogenase gene (bhbA3) and the extra-cytoplasmic binding receptor gene (bhbB3), were also found in strain EOB-17 by genome sequencing. The optimal temperature and pH for DBHB reductive dehalogenation activity are 30 degrees C and 8, respectively, and 0.1 mM Cd(2+), Cu(2+), Hg(2+) and Zn(2+) strongly inhibited dehalogenation activity. CONCLUSIONS: The aerobic strain of Delftia sp. EOB-17 was confirmed to reductively dehalogenate DBHB under aerobic conditions, providing another evidence to support the hypothesis that reductive dehalogenation occurs extensively in aerobic bacteria. PMID- 26264244 TI - Unplanned extubation: securing the tool of our trade. PMID- 26264245 TI - Epidemiology of gastrointestinal bleeding in adult patients on extracorporeal life support. PMID- 26264246 TI - Colistin-tigecycline versus colistin-imipenem-cilastatin combinations for the treatment of Acinetobacter baumannii ventilator-acquired pneumonia: a prognosis study. PMID- 26264247 TI - Fragility fractures of the pelvis: treatment and preliminary results. AB - BACKGROUND: With increasing life expectancy, fragility fractures of the pelvic ring (FFP) are becoming frequent. In elderly, osteoporosis leads to a decrease of bone strength and resistance to the ligament's traction; this represents the most important difference between FFP and fractures in young patients. Usually, these fractures are underestimated and treatment is often conservative. AIMS: To evaluate clinical and surgical outcomes of surgically treated patients with FFP. METHODS: We retrospectively enrolled 14 patients, in our Trauma Center, underwent surgery procedures for FFP between 2012 and 2014. All patients attended clinical and radiological investigation at 1, 3, and 6 months postoperatively and every year after surgery with a mean follow-up of 22 months. RESULTS: At 6-month follow up, 11 patients resulted asymptomatic: able to maintain standing position and walk without crunches. Two patients were able to walk with one crunch. The patient with history of previous acetabular fracture walks with two crunches and is still waiting for total hip arthroplasty. DISCUSSION: The compromised health status and the diminished bone-healing capacity, in elderly, decrease chances for a good clinical outcome. In literature, many authors suggest that mortality rate in patients with FFP is similar to those with hip fracture. Diagnosis of FFP is very important: these fractures are highly disabling in elderly and can lead to displacement and instability. For these reasons, correct diagnosis and well conduct preoperative plan are necessary to improve stability of fractures and support bone healing. After diagnosis, an anti-osteoporotic treatment is indicated to improve bone quality and bone healing. CONCLUSIONS: Our study shows encouraging results and demonstrates that minimally or less invasive osteosynthesis technique could lead to good outcome in these patients. PMID- 26264248 TI - Chronic kidney disease and cognitive impairment among the very old in China. AB - BACKGROUND AND AIMS: Previous studies have confirmed that chronic kidney disease (CKD) influences the cognitive function of adults. However, few studies focused the relationships among the very old. The purpose of this study was to determine whether CKD is associated with cognitive impairment among nonagenarians and centenarians in China. METHOD: This work was conducted as a cross-sectional study. 767 unrelated Chinese nonagenarians and centenarians participated in the study. The 30-item mini-mental state examination (MMSE) was used to assess cognitive function. Estimated glomerular filtration rate (eGFR) was estimated using the Modification of Diet in Renal Disease equation (Chinese version). CKD was defined as eGFR less than 60 mL/min/1.73 m(2). RESULTS: The cohort was 68.2 % female and mean (SD) age was 93.8 (3.5) years. There were 113 (14.7 %) and 577 (75.2 %) prevalent cases of CKD and cognitive impairment, respectively. After adjusting for sociodemographic variables, multivariate logistic regression showed CKD was not significantly associated with cognitive impairment (OR 0.81, 95 % CI 0.49-1.33). When other disease-related variables were adjusted, the result remained substantially unchanged. However, age, gender, education and income may largely or entirely explain the lack of association between CKD and cognitive impairment as measured according to the MMSE. CONCLUSION: Among Chinese nonagenarians and centenarians, CKD was not directly correlated with cognitive impairment. PMID- 26264249 TI - Echinococcus canadensis transmission in the North. AB - The Echinococcus granulosus complex (EG) is the causative agent of cystic echinococcosis (CE). Northern cervid Echinococcus was previously suggested to be the ancestor of the entire EG. During the last century, it was regarded to have three (or four) different, but often overlapping, transmission cycles in the circumpolar North: the original wolf-wild cervid (reindeer or elk)-cycle; the semi-synanthropic cycle involving sled and hunting dogs and wild cervids; and the synanthropic cycle involving herding dogs and semi-domesticated reindeer. Human infections mainly derived from the latter two cycles. In Fennoscandia, the synanthropic cycle has been eliminated during the last 50 years due to changes in reindeer husbandry methods; machinery making herding dogs largely redundant. Typical to human CE in the North has been the relatively benign nature of the disease compared with CE caused by E. granulosus sensu stricto. The metacestodes in humans and in the natural cervid hosts predominantly appear in the lungs. The causative agents have been identified as EG mitochondrial genotypes G8 and G10, now together with G6 (camel), G7 (pig) and G9 genotypes constituting the Echinococcus canadensis species. Based on recent findings in reindeer in Yakutia, G6 might also be recognised among cervid genotypes. The geographical distribution of both G8 and G10 is circumpolar, with G10 currently apparently more prevalent both in the Palearctic and Nearctic. Because of the disappearance of the working dog, E. canadensis in Fennoscandia is again highly dependent on the wolf, as it was before domestication of the dog. Pet and sled dogs, if their number further increases, may to a minor part participate in the life cycle. Human CE in the North was mostly diagnosed by mass chest tuberculosis radiography campaigns, which have been discontinued. PMID- 26264250 TI - Taxonomy and molecular epidemiology of Echinococcus granulosus sensu lato. AB - Echinococcus granulosus, formerly regarded as a single species with a high genotypic and phenotypic diversity, is now recognised as an assemblage of cryptic species, which differ considerably in morphology, development, host specificity (including infectivity/pathogenicity for humans) and other aspects. This diversity is reflected in the mitochondrial and nuclear genomes and has led to the construction of phylogenetic trees and hypotheses on the origin and geographic dispersal of various taxa. Based on phenotypic characters and gene sequences, E. granulosus (sensu lato) has by now been subdivided into E. granulosus sensu stricto (including the formerly identified genotypic variants G1 3), Echinococcus felidis (the former 'lion strain'), Echinococcus equinus (the 'horse strain', genotype G4), Echinococcus ortleppi (the 'cattle strain', genotype G5) and Echinococcus canadensis. The latter species, as recognised here, shows the highest diversity and is composed of the 'camel strain', genotype G6, the 'pig strain', genotype G7, and two 'cervid strains', genotypes G8 and G10. There is debate whether the closely related G6 and G7 should be placed in a separate species, but more morphological and biological data are needed to support or reject this view. In this classification, the application of rules for zoological nomenclature led to the resurrection of old species names, which had before been synonymised with E. granulosus. This nomenclatural subdivision of the agents of cystic echinococcosis (CE) may appear inconvenient for practical applications, especially because molecular tools are needed for identification of the cyst stage, and because retrospective data on 'E. granulosus' are now difficult to interpret without examination of voucher specimens. However, the increased awareness for the diversity of CE agents - now emphasised by species names rather than genotype numbers - has led to a large number of recent studies on this issue and a rapid increase of knowledge on geographical spread, host range and impact on human health of the various species. E. granulosus s.s., often transmitted by sheep, is now clearly identified as the principal CE agent affecting humans. Contrary to previous assumptions, genotypes G6/7 of E. canadensis readily infect humans, although CE incidences are rather low where E. canadensis predominates. Sub-Saharan Africa seems to be the region with the highest diversity of Echinococcus, and wild carnivores may play a more important role in the lifecycles of various species than previously assumed. Still, a number of issues remain unclear, e.g. possibly diverging parameters of diagnostic tests among the species, different responses to vaccines and, importantly, possibly required modifications of clinical management due to differences in pathogenicity. PMID- 26264251 TI - Trichinella britovi from domestic to wild animals of Sardinia, Italy. AB - The zoonotic nematode Trichinella britovi has been documented in animals and/or humans of the Mediterranean islands of Corsica and Sardinia since 2004. From 2005 to 2007 in the Sardinia island, several surveys had shown that T. britovi was circulating among backyard and free-ranging pigs reared in the Orgosolo municipality but all attempts had failed to detect this parasite in wild susceptible animals. The aim of the present work was to investigate the circulation of T. britovi in pigs and wildlife of the Orgosolo municipality, and of surrounding municipalities and provinces in the 2010-2014 slaughtering/hunting seasons. The results show that the T. britovi circulation was still restricted to the Orgosolo municipality with a prevalence of 2.6% in free-ranging pigs and 0.2% in backyard pigs but, for the first time, this parasite was detected also in 0.4% of wild boar, and 27.6% of red foxes. No infection was detected in backyard pigs, wild boar, and red foxes of the other municipalities and provinces. Since 1978, African swine fever is endemic in Sardinia and foci of this virus are still active in the investigated areas favoring cannibalism and, consequently, the T. britovi transmission, due to the high mortality rate caused by this virus. This is the first documented report on the transmission of T. britovi between the domestic and the sylvatic cycle. The health authority of the island must provide a service to dispose animal carcasses and offal, stamping out illegal free ranging pigs, and train hunters and pig owners to manage waste and by-products according to the EU regulations. PMID- 26264252 TI - Participation in muscle-strengthening activities as an alternative method for the prevention of multimorbidity. AB - OBJECTIVE: Participating in muscle-strengthening activities (MSA) has been shown to reduce the risks associated with many individual chronic diseases; however, the impact of MSA on multimorbidity remains unexplored. Therefore, the purpose of this study was to determine the association between MSA and multimorbidity. METHODS: Data from the 2003-2006 NHANES were used including 4587 adults (>=20 years old). Participation in MSA was defined as self-reported involvement within the last 30 days. Multimorbidity was deemed as having >=2 of the 14 chronic diseases. RESULTS: After adjustments (including accelerometry-assessed physical activity), individuals participating in MSA had a 26% reduced odds of having multimorbidity (OR=0.74; 95% CI: 0.62-0.88; p=0.001) and each 2 day/week increase in MSA was associated with an 8% reduced odds of being multimorbid (OR=0.92; 95% CI: 0.84-1.00; p=0.05). CONCLUSION: Independent of accelerometry-assessed physical activity, the participation in MSA may reduce the odds of being multimorbid, with evidence of a dose-response relationship. PMID- 26264253 TI - Predictive factors for 24 weeks sustained virologic response (SVR24) and viral relapse in patients treated with simeprevir plus peginterferon and ribavirin. AB - BACKGROUND: Simeprevir with peginterferon and ribavirin has been used for the treatment of chronic hepatitis caused by genotype 1 hepatitis C virus (HCV). We explored the predictive factors for sustained virological response (SVR) and viral relapse using datasets from four Japanese phase 3 studies (CONCERTO). METHODS: We used a multiple logistic regression model. First, an integrated dataset comprising 357 patients was analyzed. Subsequently, prior treatment-naive and relapser (223 patients) and nonresponder (134 patients) of interferon-based treatment subsets were analyzed to identify predictors of SVR. A subset of nonresponders (106 patients) who were treated >=24 weeks was also analyzed to identify predictors for viral relapse. RESULTS: In the integrated dataset, prior treatment response was significantly associated with SVR. In subset analyses, interleukin-28B (IL28B) TT genotype and undetectable plasma HCV RNA level at week 4 were associated in treatment-naive patients and relapsers [odds ratio (OR); 4.106 and 3.701, respectively]. In the nonresponders, the IL28B TT genotype population was very small, and inosine triphosphatase (ITPA) and undetectable plasma HCV RNA at week 4 were associated (OR; 2.506 and 3.333, respectively). Furthermore, ribavirin dose intensity (RBV-DI) and detectable plasma HCV RNA at week 4 were significantly associated with viral relapse (OR; 0.327 and 2.922, respectively). CONCLUSION: IL28B and plasma HCV RNA level at week 4 were clinically relevant predictive factors for SVR in treatment-naive patients and relapsers. Moreover, RBV-DI and plasma HCV level at week 4 were identified as relevant predictive factors for viral relapse in nonresponders. PMID- 26264254 TI - Transcriptome of the Antarctic amphipod Gondogeneia antarctica and its response to pollutant exposure. AB - Gondogeneia antarctica is widely distributed off the western Antarctic Peninsula and is a key species in the Antarctic food web. In this study, we performed Illumina sequencing to produce a total of 4,599,079,601 (4.6Gb) nucleotides and a comprehensive transcript dataset for G. antarctica. Over 46 million total reads were assembled into 20,749 contigs, and 12,461 annotated genes were predicted by Blastx. The RNA-seq results after exposure to three pollutants showed that 658, 169 and 367 genes that were potential biomarkers of responses to pollutants for this species were specifically upregulated after exposure to PCBs (Polychlorinated biphenyls), PFOS (Perfluorooctanesulfonic acid) and PFOA (Perfluorooctanoic acid), respectively. These data represent the first transcriptome resource for the Antarctic amphipod G. antarctica and provide a useful resource for studying Antarctic marine species. PMID- 26264255 TI - Age-related differences in muscle recruitment and reaction-time performance. AB - Previously, we showed that prolonged reaction-time (RT) in older persons is related to increased antagonist muscle co-activation, occurring already before movement onset. Here, we studied whether a difference in temporal agonist and antagonist muscle activation exists between young and older persons during an RT test. We studied Mm. Biceps (antagonist muscle) & Triceps (agonist muscle) Brachii activation time by sEMG in 60 young (26 +/- 3 years) and 64 older (80 +/- 6 years) community-dwelling subjects during a simple point-to-point RT-test (moving a finger using standardized elbow-extension from one pushbutton to another following a visual stimulus). RT was divided in pre-movement-time (PMT, time for stimulus processing) and movement-time (MT, time for motor response completion). Muscle activation time 1) following stimulus onset (PMAT) and 2) before movement onset (MAT) was calculated. PMAT for both muscles was significantly longer for the older subjects compared to the young (258 +/- 53 ms versus 224 +/- 37 ms, p=0.042 for Biceps and 280 +/- 70 ms versus 218 +/- 43 ms for Triceps, p<0.01). Longer agonist muscle PMAT was significantly related to worse PMT and RT in young (respectively r=0.76 & r=0.68, p<0.001) and elderly (respectively r=0.42 & r=0.40, p=0.001). In the older subjects we also found that the antagonist muscle activated significantly earlier than the agonist muscle ( 22 +/- 55 ms, p=0.003). We conclude that in older persons, besides the previously reported increased antagonist muscle co-activation, the muscle firing sequence is also profoundly altered. This is characterized by a delayed muscle activation following stimulus onset, and a significantly earlier recruitment of the antagonist muscle before movement onset. PMID- 26264256 TI - Concurrent Acoustic Activation of the Medial Olivocochlear System Modifies the After-Effects of Intense Low-Frequency Sound on the Human Inner Ear. AB - >Human hearing is rather insensitive for very low frequencies (i.e. below 100 Hz). Despite this insensitivity, low-frequency sound can cause oscillating changes of cochlear gain in inner ear regions processing even much higher frequencies. These alterations outlast the duration of the low-frequency stimulation by several minutes, for which the term 'bounce phenomenon' has been coined. Previously, we have shown that the bounce can be traced by monitoring frequency and level changes of spontaneous otoacoustic emissions (SOAEs) over time. It has been suggested elsewhere that large receptor potentials elicited by low-frequency stimulation produce a net Ca(2+) influx and associated gain decrease in outer hair cells. The bounce presumably reflects an underdamped, homeostatic readjustment of increased Ca(2+) concentrations and related gain changes after low-frequency sound offset. Here, we test this hypothesis by activating the medial olivocochlear efferent system during presentation of the bounce-evoking low-frequency (LF) sound. The efferent system is known to modulate outer hair cell Ca(2+) concentrations and receptor potentials, and therefore, it should modulate the characteristics of the bounce phenomenon. We show that simultaneous presentation of contralateral broadband noise (100 Hz-8 kHz, 65 and 70 dB SPL, 90 s, activating the efferent system) and ipsilateral low-frequency sound (30 Hz, 120 dB SPL, 90 s, inducing the bounce) affects the characteristics of bouncing SOAEs recorded after low-frequency sound offset. Specifically, the decay time constant of the SOAE level changes is shorter, and the transient SOAE suppression is less pronounced. Moreover, the number of new, transient SOAEs as they are seen during the bounce, are reduced. Taken together, activation of the medial olivocochlear system during induction of the bounce phenomenon with low frequency sound results in changed characteristics of the bounce phenomenon. Thus, our data provide experimental support for the hypothesis that outer hair cell calcium homeostasis is the source of the bounce phenomenon. PMID- 26264257 TI - Risk factor analysis of recurrence in low-grade endometrial adenocarcinoma. AB - Prognosis of endometrial adenocarcinoma is favorable; however, the risk of recurrence ranges from 7% to 13%. Recurrence has been related to age, tumor type, International Federation of Gynecology and Obstetrics grade, depth of invasion, and lymphovascular invasion (LVI); however, morphologic features that would predict the site of recurrence have not been established. In this multi institutional study, we reviewed 589 patients with International Federation of Gynecology and Obstetrics grades 1 or 2 endometrial adenocarcinoma, endometrioid type. Cox proportional hazard analysis was used to identify univariate and multivariate risk factors for recurrence and survival. Univariate analysis revealed features of tumors that recurred only in the vagina: low nuclear grade; superficial myoinvasion; minimal to no LVI; and minimal myoinvasion with microcystic, elongated, and fragmented (MELF) pattern; low nuclear grade and superficial myoinvasion persisted on multivariate analysis. Features of tumors that recurred at other sites included large size, deep myoinvasion, tumor necrosis, 1 or more LVI foci, LVI foci distant/deeper than invasive tumor front, MELF myoinvasion pattern, lower uterine segment and cervical stromal involvement, pelvic and/or paraaortic lymph node metastases at presentation, and higher grade of tumor in the metastatic foci, whereas increased percentage of solid component and lower percentage of mucinous features were marginally associated. Tumors with recurrences only in vagina had different features than tumors that recurred at other sites. The presence of tumor necrosis, MELF foci at the invasive tumor front, and the percentage of solid component and mucinous features could be helpful in grading endometrioid adenocarcinomas, if a 2-tier rather than a 3-tier grading system is accepted in the future. PMID- 26264258 TI - Substance Use and Risky Sexual Behaviors Among Young Men Working at a Rural Roadside Market in Malawi. AB - Using an ecological model, we describe substance use and sexual risk behaviors of young male laborers at a roadside market in Malawi. Data included observations and interviews with 18 key market leaders and 15 laborers (ages 18-25 years). Alcohol, marijuana, and commercial sex workers (CSWs) were widely available. We identified three patterns of substance use: 6 young men currently used, 6 formerly used, and 3 never used. Substance use was linked to risky sex, including sex with CSWs. The market supported risky behaviors through availability of resources; supportive norms, including beliefs that substance use enhanced strength; and lack of restraints. Community-level poverty, cultural support for alcohol, interpersonal family/peer influences, early substance use, and school dropout also contributed to risky behaviors. Parental guidance was protective but not often reported. Local programs addressing substance use and risky sex simultaneously and better national substance use policies and mental health services are needed. PMID- 26264259 TI - Effects of ketanserin on microcirculatory alterations in septic shock: An open label pilot study. AB - INTRODUCTION: Microcirculatory alterations in sepsis are associated with increased morbidity and mortality. These alterations occur despite macrohemodynamic resuscitation. Alternative pro-microcirculatory strategies, including vasodilatory drugs, have been suggested to improve capillary blood flow. Ketanserin, a serotonin receptor antagonist, is an attractive candidate because of its vasodilatory, antithrombotic, and anti-inflammatory effects. METHODS: This is an open-label pilot study on the effect of ketanserin administration on microcirculatory alterations in septic shock, defined as microvascular flow index (MFI)<=2.5 after a strict macrohemodynamic resuscitation protocol. Sidestream dark-field imaging was applied to assess the microcirculation. A stepwise incremental dose regiment was applied until an MFI>2.9, the primary end point, was reached. RESULTS: Ten patients (Acute Physiology and Chronic Health Evaluation IV scores of 115 [100-136]) were included. Baseline MFI was 1.71 (1.31-2.32) and was significantly increasing to 2.96 (2.54-3.00; P=.021) during the ketanserin infusion. The total ketanserin dose was 0.09 (0.08-0.13) mg/kg per patient in 60 (30-60) minutes. In 3 patients (30%), the ketanserin infusion was discontinued due to refractory hypotension. CONCLUSION: An improvement in microcirculatory perfusion was observed during ketanserin administration in patients with septic shock after macrohemodynamic resuscitation. This finding needs further exploration in a placebo-controlled setting. PMID- 26264260 TI - Activity of several kinds of drugs against Neospora caninum. AB - Neosporosis caused by Neospora caninum is a serious disease in cattle and dogs worldwide. It is the major cause of abortion and neonatal mortality in cattle. In this study, we evaluated the anti-N. caninum activity of Chinese medicine extracts (curcumin, artemether), herbicides (atrazine, glyphosate), anticoccidiosis drugs (toltrazuril and ponazuril), cyclophosphamide, diminazene aceturate and praziquantel in vitro using parasite growth, replication and host cell invasion assays in human foreskin fibroblast cultures. Curcumin, artemether, atrazine, toltrazuril and ponazuril exhibited inhibitory activity with 50% growth inhibitory concentration (IC50) of 1.1+/-0.4, 1.0+/-0.05, 11.2+/-2.7, 30.3+/-2.0 and 33.3+/-4.1MUg/ml, respectively, in the growth inhibition assay. They were also active against protozoa replication, but only curcumin was effective against host cell invasion. Glyphosate, cyclophosphamide, diminazene aceturate and praziquantel were ineffective. In an in vivo infection model, curcumin showed no activity against N. caninum infection. We showed that curcumin, artemether, atrazine, toltrazuril, and ponazuril exhibited anti-N. caninum activity in vitro, providing important information for further studies on anti-N. caninum drugs. PMID- 26264261 TI - Congenital toxoplasmosis and pregnancy malaria detection post-partum: Effective diagnosis and its implication for efficient management of congenital infection. AB - Congenital toxoplasmosis (CT) and pregnancy malaria (PM) have been individually reported to cause severe negative outcomes in pregnancies but the diagnostic method is still debatable. This study sought to estimate the prevalence of PM and CT single and co-infections in pregnant women by using various specimens including plasma and placental tissues. Genomic DNA extracted from the placenta, cord blood or blood of mothers was tested by PCR. Conventional method of immunodiagnosis was done for CT. We tested 79 pregnant women aged 18-42 years (mean: 28+/-1.06). Prevalence of Plasmodium falciparum infection determined by PCR on mother's peripheral blood specimen was 6.3% whiles 57.3% was recorded for placental tissues (p<0.01). PCR testing for placental tissues showed 29.2% positive for Toxoplasma gondii, whiles 76.0% of mothers had serum IgG against T. gondii. It should be noted that 6.3% of the placental tissues showed PCR positive for SAG 3, a marker of active infection in T. gondii. Although there were no enhanced foetal disorders at birth in our study, there is a possibility of active transmission of T. gondii from mothers to foetuses even in immune mothers. Our study suggests that foetuses were exposed to P. falciparum and T. gondii in utero, and placenta is a better specimen for PCR in detecting such episodes. In cases of PCR-positive samples, clinical follow-up after birth may be important. PMID- 26264262 TI - Increased Oxidative Damage and Reduced DNA Repair Enzyme XPD Involvement in High Glucose-Mediated Enhancement of Levobupivacaine-Induced Neurotoxicity. AB - Levobupivacaine is one of the major clinical local anesthetics, but it can cause neuron toxic damage. Hyperglycemia can cause neuronal DNA oxidative damage and inhibit expression of the DNA repair gene Xeroderma pigmentosum complementation group D (XPD). This study was designed to determine whether high glucose levels inhibit XPD expression and enhance levobupivacaine-induced DNA damage. We evaluated XPD mRNA and protein expression in SH-SY5Y cells after glucose and levobupivacaine exposure. We next investigated cells reactive oxygen species (ROS) levels, DNA damage and apoptosis with redox-sensitive fluorescent dye DCFH DA (2',7'-dichlorofluorescein diacetate), comet assays, flow cytometry, and TUNEL (terminal deoxynucleotidyl transferased UTP nick end labeling) assays. XPD expression was inhibited in cells exposed to prolonged high glucose with a concomitant increase in ROS production and more severe DNA damage compared to control culture conditions, and these changes were further exacerbated by levobupivacaine. Our findings indicate that subjects with diabetes may experience more detrimental effects following local anesthetic use. PMID- 26264263 TI - Electrochemical magneto-actuated biosensor for CD4 count in AIDS diagnosis and monitoring. AB - The counting of CD4(+) T lymphocytes is a clinical parameter used for AIDS diagnosis and follow-up. As this disease is particularly prevalent in developing countries, simple and affordable CD4 cell counting methods are urgently needed in resource-limited settings. This paper describes an electrochemical magneto actuated biosensor for CD4 count in whole blood. The CD4(+) T lymphocytes were isolated, preconcentrated and labeled from 100 MUL of whole blood by immunomagnetic separation with magnetic particles modified with antiCD3 antibodies. The captured cells were labeled with a biotinylated antiCD4 antibody, followed by the reaction with the electrochemical reporter streptavidin peroxidase conjugate. The limit of detection for the CD4 counting magneto actuated biosensor in whole blood was as low as 44 cells MUL(-1) while the logistic range was found to be from 89 to 912 cells MUL(-1), which spans the whole medical interest range for CD4 counts in AIDS patients. The electrochemical detection together with the immunomagnetic separation confers high sensitivity, resulting in a rapid, inexpensive, robust, user-friendly method for CD4 counting. This approach is a promising alternative for the costly standard flow cytometry and suitable as diagnostic tool at decentralized practitioner sites in low resource settings, especially in less developed countries. PMID- 26264264 TI - A reusable optical biosensor for the ultrasensitive and selective detection of unamplified human genomic DNA with gold nanostars. AB - A Surface Plasmon Resonance imaging (SPRi) based DNA sensors for the selective and ultrasensitive human genomic DNA detection, directly extracted from lymphocytes (bypassing PCR amplification), is reported. To achieve DNA detection, a rationally chosen star-shaped nanoparticle (NP), namely gold nanostar (AuNS), has been applied, for the first time, in a sandwich-like assay based on the selective capturing of specific DNA targets and the subsequent signal amplification by a secondary DNA probe linked to AuNS. The plasmonic profile, size and electric field enhancements at the star tips contributed to the maximization of plasmon coupling between LSPs and SPs as aimed for analytical signal magnification. The system was first tested using short synthetic DNA target sequences and applied to DNA biosensing, lowering 610-fold the detection limit from 6.1 nM (without NSs labeling) to 10 pM (with NSs labeling). Then the biosensor was applied to genomic DNA samples, extracted from human lymphocytes and undergoing only to a simple ultrasonic fragmentation, lowering (~435 fold) the detection limit from 3.0 fM (without NSs labeling) to 6.9 aM (with NSs labeling). Thanks to the assay optimization, we proved that tuning the NSs surface coverage with DNA linked to nanoparticles is crucial not only for the increase of signals but also for the regenerability/reusability of the biosensor for tens of measurement cycles. PMID- 26264265 TI - The performance and mechanism of modified activated carbon air cathode by non stoichiometric nano Fe3O4 in the microbial fuel cell. AB - Cathodic catalyst is one of the key materials in microbial fuel cell (MFC). The addition of non-stoichiometric nano Fe3O4 in activated carbon (NSFe3O4/AC) air cathode was beneficial to boosting the charge transfer of the cathode accompanying with the enhancement of power performance in MFC. The air cathode modified by NSFe3O4 (5%, Wt%) increased the maximum power density by 83.3% from 780 mW/m(2) to 1430 mW/m(2) compared with bare air cathode. The modified cathodes showed enhanced electrochemical properties and appeared the maximum exchange current density of 18.71*10(-4) A/cm(2) for oxygen reduction reaction. The mechanism of oxygen reduction for the NSFe3O4/AC catalyst was a 4-electron pathway. The oxygen vacancy of the NSFe3O4 played a crucial role in electrochemical catalytic activity. The great catalytic performance made NSFe3O4 have a promising outlook applied in MFC. PMID- 26264266 TI - Comparative investigations for adenovirus recognition and quantification: Plastic or natural antibodies? AB - Comparative and comprehensive investigations for adenovirus recognition and detection were conducted using plastic and natural antibodies to compare three different strategies. The implementation of molecularly imprinted polymer (MIP) technology for specific and sensitive recognition of viruses with the combination of biosensors was reported. Plastic antibodies (MIPs nanoparticles) were produced for adenovirus by employing a novel solid phase synthesis method. MIP receptors were then characterised using dynamic light scattering (DLS) and transmission electron microscopy (TEM) techniques prior to immobilisation on a surface plasmon resonance (SPR) sensor as affinity receptor for adenovirus detection. Two different templates were also imprinted as control MIPs (vancomycin-MIP and MS2 MIP). The specific recognition of adenovirus was investigated in the concentration range of 0.01-20 pM and the limit of detection was achieved as 0.02 pM. As an alternative to MIP receptors, direct and sandwich assays were developed for adenovirus quantification using natural antibodies. The detection limit of direct and sandwich assays were found as 0.3 pM and 0.008 pM, respectively. The kinetic data analyses were performed for three different adenovirus recognition methods and cross-reactivity studies were also conducted using MS2 phage as control virus and an excellent specificity was achieved with all assays types. This work confirmed the suitability of the MIPs SPR sensor for the detection of viruses. PMID- 26264267 TI - Novel signal amplification approach for HRP-based colorimetric genosensors using DNA binding protein tags. AB - The need for sensitive detection of DNA is growing as more specific DNA sequences are being correlated to gene markers for disease diagnosis, food safety and other security related applications. Detection in hybridization-based assays is usually achieved with target-specific ssDNA probes conjugated directly to enzyme labels like HRP that provide signal amplification or with nanoparticles functionalized with DNA and multiple HRP molecules. In order to overcome some of the drawbacks presented by these approaches, we developed a unique DNA sensing platform based on an HRP-DNA binding protein tag conjugate and a hybrid ssDNA-dsDNA detection probe. Specifically, in this work we describe the preparation and characterization of an HRP conjugate with scCro DNA binding protein tag and its application for the detection of a model ssDNA target sequence. By using the HRP scCro conjugate together with a hybrid detection probe containing three scCro specific dsDNA binding sites, we demonstrate an improvement by over 3-fold in both sensitivity and limit of detection of high-risk human papillomavirus (HPV16), compared to the standard ssDNA-HRP conjugate. These results show that the HRP-DNA binding protein tag conjugate can be used as an alternative and universal tool for signal enhancement in enzyme-linked assays suitable for integration in point-of-care systems. PMID- 26264268 TI - A microfluidic device for label-free detection of Escherichia coli in drinking water using positive dielectrophoretic focusing, capturing, and impedance measurement. AB - While sensors that allow for high-throughput enumeration of microorganisms within drinking water are useful for water quality monitoring, it is particularly challenging to accurately quantify microorganisms that are present in low numbers (<100 CFU/mL) in a high-throughput manner. Negative dielectrophoresis (nDEP) is typically utilized in DEP-based cell focusing methods; however, due to its low conductivity, drinking water cannot be analyzed by this approach. Here, we report a positive DEP (pDEP)-based Escherichia coli detection system that is integrated with a focusing and sensing electrode. By incorporating a passivation layer, we avoided issues with adhesion of E. coli to the electrode, and achieved efficient cell focusing under high flow rate conditions (1500 MUL/h). The resulting focused E. coli cells were then trapped on the sensor electrode, resulting in changes in impedance. The proposed system was evaluated using four different E. coli populations (150-1500 CFU/mL). We successfully enumerated populations as low as 300 CFU/mL within 1 min, and the signal variation was 1.13+/-0.37%. The device introduced in this study provides the basis for the development of portable, highly sensitive microorganism sensors that enable rapid detection of bacteria in drinking water. PMID- 26264269 TI - A label-free photoelectrochemical aptasensor based on nitrogen-doped graphene quantum dots for chloramphenicol determination. AB - A photoelectrochemical (PEC) sensing platform for chloramphenicol (CAP) detection was constructed using nitrogen-doped graphene quantum dots (N-GQDs) as transducer species and label-free aptamer as biological recognition element. N-GQDs, synthesized via a facile one-step hydrothermal method, were explored to achieve highly efficient photon-to-electricity conversion under visible light irradiation. The obtained N-GQDs were characterized by transmission electron microscopy (TEM), which displayed a narrow size distribution with a mean diameter of 2.14 nm. The X-ray photoelectron spectroscopic (XPS) and Fourier transform infrared spectroscopic (FT-IR) analysis confirmed that nitrogen was successfully doped in GQDs. The UV-visible absorption spectra indicated that nitrogen doping obviously enhanced the absorption of GQDs in visible light region. As a result, the PEC activity of GQDs was promoted by nitrogen doping. Additionally, the pi conjugated structure of N-GQDs provided an excellent platform for aptamer immobilization via pi-pi stacking interaction. Such an aptamer/N-GQDs based sensor showed a linear PEC response to CAP concentration in the range of 10-250 nM with a detection limit (3 S/N) of 3.1 nM. The developed PEC aptasensor exhibited high sensitivity and selectivity, good reproducibility and high stability. PMID- 26264270 TI - TiO2 nanoparticle modified organ-like Ti3C2 MXene nanocomposite encapsulating hemoglobin for a mediator-free biosensor with excellent performances. AB - TiO2 nanoparticle modified organ-like Ti3C2 MXene (TiO2-Ti3C2) nanocomposite has been synthesized and then used to immobilize hemoglobin (Hb) to fabricate a mediator-free biosensor. The morphology and structure of TiO2-Ti3C2 nanocomposite were characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). Spectroscopic and electrochemical results revealed that TiO2-Ti3C2 nanocomposite is an excellent immobilization matrix with biocompatibility for redox protein, affording good protein bioactivity and stability. Due to the special organ-like hybrid structure of TiO2-Ti3C2, the direct electron transfer of Hb is facilitated and the prepared biosensors displayed good performance for the detection of H2O2 with a wide linear range of 0.1-380 MUM for H2O2 (sensitivity of 447.3 MUA mM(-1) cm(-2)), an extremely low detection limit of 14 nM for H2O2. Especially, numerous TiO2 nanoparticles with excellent biocompatibility on the surface of the nanocomposite may provide a protective microenvironment for Hb to make the prepared biosensor improve long-term stability. The TiO2-Ti3C2 based biosensor retains 94.6% of the initial response to H2O2 after 60-day storage. TiO2-Ti3C2 nanocomposite could be a promising matrix for the fabrication of mediator-free biosensors, and might find wide potential applications in environmental analysis and biomedical detection. PMID- 26264272 TI - Prescribing for Australians living with dementia: study protocol using the Delphi technique. AB - INTRODUCTION: Prescribing is complicated for people living with dementia, and careful consideration should be given to continuing and initiating all medicines. This study aims to elicit opinion and gain consensus on appropriate medicine use for people living with dementia in Australia to create a consensus-based list of explicit prescribing criteria. METHODS AND ANALYSIS: A Delphi technique will be used to develop explicit criteria of medication use in adults aged 65 years and above. An interdisciplinary panel of Australian experts in geriatric therapeutics will be convened that will consist of a minimum of 10 participants. To develop the consensus-based criteria, this study will use an iterative, anonymous, multistaged approach with controlled feedback. Round 1 questionnaire will be administered, and subsequently qualitatively analysed. The round 1 results will be fed back to the panel members, and a round 2 questionnaire developed using questions on a five-point Likert scale. This process will repeat until consensus is developed, or diminishing returns are noted. ETHICS AND DISSEMINATION: All participants will be provided with a participant information sheet, and sign a written consent form. Ethical approval has been granted from the University of Western Australia's Human Research Ethics Committee (HREC) (reference: RA/4/1/7172). We expect that data from this study will result in a paper published in a peer-reviewed clinical journal and will also present the results at conferences. PMID- 26264273 TI - Relationship between individual characteristics, neighbourhood contexts and help seeking intentions for mental illness. AB - OBJECTIVE: Encouraging help-seeking for mental illness is essential for prevention of suicide. This study examined the relationship between individual characteristics, neighbourhood contexts and help-seeking intentions for mental illness for the purpose of elucidating the role of neighbourhood in the help seeking process. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional web-based survey was conducted among Japanese adults aged 20-59 years in June 2014. Eligible respondents who did not have a serious health condition were included in this study (n=3308). MAIN OUTCOME MEASURES: Participants were asked how likely they would be to seek help from someone close to them (informal help) and medical professionals (formal help), respectively, if they were suffering from serious mental illness. Path analysis with structural equation modelling was performed to represent plausible connections between individual characteristics, neighbourhood contexts, and informal and formal help-seeking intentions. RESULTS: The acceptable fitting model indicated that those who had a tendency to consult about everyday affairs were significantly more likely to express an informal help seeking intention that was directly associated with a formal help-seeking intention. Those living in a communicative neighbourhood, where neighbours say hello whenever they pass each other, were significantly more likely to express informal and formal help-seeking intentions. Those living in a supportive neighbourhood, where neighbours work together to solve neighbourhood problems, were significantly more likely to express an informal help-seeking intention. Adequate health literacy was directly associated with informal and formal help seeking intentions, along with having an indirect effect on the formal help seeking intention through developed positive perception of professional help. CONCLUSIONS: The results of this study bear out the hypothesis that neighbourhood context contributes to help-seeking intentions for mental illness. Living in a neighbourhood with a communicative atmosphere and having adequate health literacy were acknowledged as possible facilitating factors for informal and formal help seeking for mental illness. PMID- 26264271 TI - Afrostyrax lepidophyllus extracts exhibit in vitro free radical scavenging, antioxidant potential and protective properties against liver enzymes ion mediated oxidative damage. AB - BACKGROUND: Several studies described the phytochemical constituents of plants in relation with the free radical scavenging property and inhibition of lipid peroxidation. This study investigated the in vitro antioxidant property, and the protective effects of ethanolic and aqueous ethanol extract of the leaves and barks of Afrostyrax lepidophyllus (Huaceae) against ion mediated oxidative damages. METHODS: Four extracts (ethanol and aqueous-ethanol) from the leaves and barks of A. lepidophyllus were used in this study. The total phenols content, the antiradical and antioxidant properties were determined using standard colorimetric methods. RESULTS: The plant extracts had a significant scavenging potential on the 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl (OH), nitrite oxide (NO) and 2,2-azinobis (3-ethylbenzthiazoline)-6-sulfonic acid (ABTS) radicals with the IC50 varied between 47 and 200 ug/mL depending on the part of plant and the type of extract. The ethanol extract of A. lepidophyllus bark (GEE) showed the highest polyphenolic (35.33 +/- 0.29) and flavonoid (12.00 +/- 0.14) content. All the tested extracts demonstrated a high protective potential with the increased of superoxide dismutase, catalase and peroxidase activities. CONCLUSION: Afrostyrax lepidophyllus extracts exhibited higher antioxidant potential and significant protective potential on liver enzymes. PMID- 26264274 TI - Patients recording clinical encounters: a path to empowerment? Assessment by mixed methods. AB - OBJECTIVE: To examine the motivations of patients recording clinical encounters, covertly or otherwise, and why some do not wish to record encounters. DESIGN: Mixed-methods analysis of survey data and nested semistructured interviews. SETTING: Survey to UK audience, using social media and radio broadcast. PARTICIPANTS: 168 survey respondents, of whom 161 were 18 years of age or older (130 completions). Of the 56 participants who agreed to be contacted, we included data from 17 interviews. RESULTS: 19 (15%) respondents indicated having secretly recorded a clinical encounter and 14 (11%) were aware of someone who had secretly recorded a clinical encounter. 45 (35%) said they would consider recording secretly and 44 (34%) said they would record after asking permission. Totally, 69% of respondents indicated their desire to record clinical encounters, split equally between wanting to do so covertly or with permission. Thematic analysis of the interviews showed that most patients are motivated by the wish to replay, relisten and share the recording with others. Some are also motivated by the idea of owning a personal record, and its potential use as verification of a poor healthcare experience. The rationale for permission seeking was based on the wish to prioritise a trusting relationship with a health professional. Those who preferred to record covertly described a pre-existing lack of trust, a fear that recording would be denied, and a concern that an affronted clinician would deny them access to future care. There was a general wish that recording should be facilitated. CONCLUSIONS: Patients' prime motivation for recording is to enhance their experience of care, and to share it with others. Patients know that recording challenges the 'ceremonial order of the clinic', and so some decide to act covertly. Patients wanted clearer, more permissive policies to be developed. PMID- 26264276 TI - Durability of Kinase-Directed Therapies--A Network Perspective on Response and Resistance. AB - Protein kinase-directed cancer therapies yield impressive initial clinical responses, but the benefits are typically transient. Enhancing the durability of clinical response is dependent upon patient selection, using drugs with more effective pharmacology, anticipating mechanisms of drug resistance, and applying concerted drug combinations. Achieving these tenets requires an understanding of the targeted kinase's role in signaling networks, how the network responds to drug perturbation, and patient-to-patient network variations. Protein kinases create sophisticated, malleable signaling networks with fidelity coded into the processes that regulate their presence and function. Robust and reliable signaling is facilitated through network processes (e.g., feedback regulation, and compensatory signaling). The routine use of kinase-directed therapies and advancements in both genomic analysis and tumor cell biology are illuminating the complexity of tumor network biology and its capacity to respond to perturbations. Drug efficacy is attenuated by alterations of the drug target (e.g., steric interference, compensatory activity, and conformational changes), compensatory signaling (bypass mechanisms and phenotype switching), and engagement of other oncogenic capabilities (polygenic disease). Factors influencing anticancer drug response and resistance are examined to define the behavior of kinases in network signaling, mechanisms of drug resistance, drug combinations necessary for durable clinical responses, and strategies to identify mechanisms of drug resistance. PMID- 26264277 TI - Sphingosine Kinase-1 Protects Multiple Myeloma from Apoptosis Driven by Cancer Specific Inhibition of RTKs. AB - Activation of acid sphingomyelinase (ASM) leads to ceramide accumulation and induces apoptotic cell death in cancer cells. In the present study, we demonstrate that the activation of ASM by targeting cancer-overexpressed 67-kDa laminin receptors (67LR) induces lipid raft disruption and inhibits receptor tyrosine kinase (RTK) activation in multiple myeloma cells. Sphingosine kinase 1 (SphK1), a negative regulator of ceramide accumulation with antiapoptotic effects, was markedly elevated in multiple myeloma cells. The silencing of SphK1 potentiated the apoptotic effects of the green tea polyphenol epigallocatechin-3 O-gallate (EGCG), an activator of ASM through 67LR. Furthermore, the SphK1 inhibitor safingol synergistically sensitized EGCG-induced proapoptotic cell death and tumor suppression in multiple myeloma cells by promoting the prevention of RTK phosphorylation and activation of death-associated protein kinase 1 (DAPK1). We propose that targeting 67LR/ASM and SphK1 may represent a novel therapeutic strategy against multiple myeloma. PMID- 26264278 TI - Gene Knockdown by EpCAM Aptamer-siRNA Chimeras Suppresses Epithelial Breast Cancers and Their Tumor-Initiating Cells. AB - Effective therapeutic strategies for in vivo siRNA delivery to knockdown genes in cells outside the liver are needed to harness RNA interference for treating cancer. EpCAM is a tumor-associated antigen highly expressed on common epithelial cancers and their tumor-initiating cells (TIC, also known as cancer stem cells). Here, we show that aptamer-siRNA chimeras (AsiC, an EpCAM aptamer linked to an siRNA sense strand and annealed to the siRNA antisense strand) are selectively taken up and knock down gene expression in EpCAM(+) cancer cells in vitro and in human cancer biopsy tissues. PLK1 EpCAM-AsiCs inhibit colony and mammosphere formation (in vitro TIC assays) and tumor initiation by EpCAM(+) luminal and basal-A triple-negative breast cancer (TNBC) cell lines, but not EpCAM(-) mesenchymal basal-B TNBCs, in nude mice. Subcutaneously administered EpCAM-AsiCs concentrate in EpCAM(+) Her2(+) and TNBC tumors and suppress their growth. Thus, EpCAM-AsiCs provide an attractive approach for treating epithelial cancer. PMID- 26264275 TI - Heavier smoking may lead to a relative increase in waist circumference: evidence for a causal relationship from a Mendelian randomisation meta-analysis. The CARTA consortium. AB - OBJECTIVES: To investigate, using a Mendelian randomisation approach, whether heavier smoking is associated with a range of regional adiposity phenotypes, in particular those related to abdominal adiposity. DESIGN: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730 in the CHRNA5-CHRNA3 CHRNB4 gene region) as a proxy for smoking heaviness, of the associations of smoking heaviness with a range of adiposity phenotypes. PARTICIPANTS: 148,731 current, former and never-smokers of European ancestry aged >= 16 years from 29 studies in the consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA). PRIMARY OUTCOME MEASURES: Waist and hip circumferences, and waist-hip ratio. RESULTS: The data included up to 66,809 never-smokers, 43,009 former smokers and 38,913 current daily cigarette smokers. Among current smokers, for each extra minor allele, the geometric mean was lower for waist circumference by 0.40% (95% CI -0.57% to -0.22%), with effects on hip circumference, waist-hip ratio and body mass index (BMI) being -0.31% (95% CI -0.42% to -0.19), -0.08% ( 0.19% to 0.03%) and -0.74% (-0.96% to -0.51%), respectively. In contrast, among never-smokers, these effects were higher by 0.23% (0.09% to 0.36%), 0.17% (0.08% to 0.26%), 0.07% (-0.01% to 0.15%) and 0.35% (0.18% to 0.52%), respectively. When adjusting the three central adiposity measures for BMI, the effects among current smokers changed direction and were higher by 0.14% (0.05% to 0.22%) for waist circumference, 0.02% (-0.05% to 0.08%) for hip circumference and 0.10% (0.02% to 0.19%) for waist-hip ratio, for each extra minor allele. CONCLUSIONS: For a given BMI, a gene variant associated with increased cigarette consumption was associated with increased waist circumference. Smoking in an effort to control weight may lead to accumulation of central adiposity. PMID- 26264280 TI - Prevalence and predictors of childhood enuresis in southwest Nigeria: Findings from a cross-sectional population study. AB - INTRODUCTION: Childhood enuresis is common, but the prevalence and factors associated with childhood enuresis in Africa have been poorly described. Furthermore, most studies from the continent have not provided data distinguishing monosymptomatic from non-monosymptomatic enuresis. This distinction is important as it guides enuresis therapy. OBJECTIVES: The primary objective of this study was to determine the prevalence of enuresis in children aged 5-17 years in a community in Nigeria. The secondary objectives were to determine the relative proportions of monosymptomatic and non-monosymptomatic enuresis and identify independent sociodemographic and clinical predictors of enuresis. STUDY DESIGN: Parents or guardians in the community were interviewed using a pretested questionnaire. Standardized definitions were used, as recommended by the International Children's Continence Society. RESULTS: A total of 928 children were included in the study. The prevalence of enuresis or daytime incontinence and enuresis was 28.3% (enuresis 24.4%, and daytime incontinence and enuresis 4%); it decreased with age. Primary and monosymptomatic enuresis were the most common types of enuresis. In multiple logistic regressions, children aged 5-9 years were 10.41 (5.14-21.05) times more likely to have enuresis or daytime incontinence and enuresis compared with those aged 14-17 years. Other predictors of enuresis or daytime incontinence and enuresis were: male gender (OR 1.56 (1.13-2.14)); constipation (OR 2.56 (1.33-4.93)); and a sibling (OR 2.20 (1.58-3.06)) or parent (OR 3.14 (2.13-4.63)) with enuresis. Enuresis or daytime incontinence and enuresis was 1.92 (1.06-3.48) times more likely in fourth-born, or higher, children compared with first-born children. Only parents of nine (3.4%) children with enuresis had consulted a medical doctor about it. DISCUSSION: The high prevalence of childhood enuresis in the present study was consistent with most studies from developing countries and contrasted sharply with the lower rates reported among children in developed countries. Common reasons for this disparity were the influence of socioeconomic status on enuresis rates and the low utilization of effective enuresis therapies in developing countries. Consistent with published literature, monosymptomatic enuresis was the commonest form of enuresis in the present study. Furthermore, younger age, male gender and a family history of enuresis were strongly associated with enuresis. A major limitation of the study was the lack of use of a voiding diary. CONCLUSION: Childhood enuresis was common in the community but parents rarely sought medical attention. Predictors of enuresis were younger age, male gender, constipation, higher birth order, and a family history of enuresis. PMID- 26264279 TI - Antiandrogen Therapy with Hydroxyflutamide or Androgen Receptor Degradation Enhancer ASC-J9 Enhances BCG Efficacy to Better Suppress Bladder Cancer Progression. AB - Recent studies suggest that the androgen receptor (AR) might play important roles in influencing bladder cancer progression, yet its clinical application remains unclear. Here, we developed a new combined therapy with Bacillus Calmette-Guerin (BCG) and the AR degradation enhancer ASC-J9 or antiandrogen hydroxyflutamide (HF) to better suppress bladder cancer progression. Mechanism dissection revealed that ASC-J9 treatment enhanced BCG efficacy to suppress bladder cancer cell proliferation via increasing the recruitment of monocytes/macrophages that involved the promotion of BCG attachment/internalization to the bladder cancer cells through increased integrin-alpha5beta1 expression and IL6 release. Such consequences might then enhance BCG-induced bladder cancer cell death via increased TNFalpha release. Interestingly, we also found that ASC-J9 treatment could directly promote BCG-induced HMGB1 release to enhance the BCG cytotoxic effects for suppression of bladder cancer cell growth. In vivo approaches also concluded that ASC-J9 could enhance the efficacy of BCG to better suppress bladder cancer progression in BBN-induced bladder cancer mouse models. Together, these results suggest that the newly developed therapy combining BCG plus ASC-J9 may become a novel therapy to better suppress bladder cancer progress. PMID- 26264281 TI - Silver Nanorods Wrapped with Ultrathin Al2O3 Layers Exhibiting Excellent SERS Sensitivity and Outstanding SERS Stability. AB - Silver nanostructures have been considered as promising substrates for surface enhanced Raman scattering (SERS) with extremely high sensitivity. The applications, however, are hindered by the facts that their morphology can be easily destroyed due to the low melting points (~100 degrees C) and their surfaces are readily oxidized/sulfured in air, thus losing the SERS activity. It was found that wrapping Ag nanorods with an ultrathin (~1.5 nm) but dense and amorphous Al2O3 layer by low-temperature atomic layer deposition (ALD) could make the nanorods robust in morphology up to 400 degrees C, and passivate completely their surfaces to stabilize the SERS activity in air, without decreasing much the SERS sensitivity. This simple strategy holds great potentials to generate highly robust and stable SERS substrates for real applications. PMID- 26264282 TI - Pathway analysis of body mass index genome-wide association study highlights risk pathways in cardiovascular disease. AB - Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. It is reported that body mass index (BMI) is risk factor for CVD. Genome-wide association studies (GWAS) have recently provided rapid insights into genetics of CVD and its risk factors. However, the specific mechanisms how BMI influences CVD risk are largely unknown. We think that BMI may influences CVD risk by shared genetic pathways. In order to confirm this view, we conducted a pathway analysis of BMI GWAS, which examined approximately 329,091 single nucleotide polymorphisms from 4763 samples. We identified 31 significant KEGG pathways. There is literature evidence supporting the involvement of GnRH signaling, vascular smooth muscle contraction, dilated cardiomyopathy, Gap junction, Wnt signaling, Calcium signaling and Chemokine signaling in CVD. Collectively, our study supports the potential role of the CVD risk pathways in BMI. BMI may influence CVD risk by the shared genetic pathways. We believe that our results may advance our understanding of BMI mechanisms in CVD. PMID- 26264283 TI - Functionalized ultrathin palladium nanosheets as patches for HepG2 cancer cells. AB - Flexible, charged Pd nanosheets were prepared by using short chain thiolated carboxylic acids and amines. They could wrap around amine or hydroxyl functionalized micron-sized spheres driven by electrostatic interactions. Upon incubation with HepG2 cells, the positively charged cysteamine (CA) functionalized Pd nanosheets exhibited a much higher cytotoxicity, showing more than 80% cell death at 100 ppm than the negatively charged 3-mercaptopropionic acid (MPA) functionalized ones which caused 30% cell death. The results show through surface functionalization Pd nanosheets can be modified to interact differently with HepG2 cancerous cells, resulting in varied cytotoxicity. PMID- 26264286 TI - Cell shapes and patterns as quantitative indicators of tissue stress in the plant epidermis. AB - In a confluent, single-cell tissue layer, we show that cell shapes and statistics correlate directly with the tissue's mechanical properties, described by an energy functional with generic interfacial terms only. Upon increasing the cohesive component of the model, we observe a clear transition from a tense state with isotropic cells to a relaxed state with anisotropic cells. Signatures of the transition are present in the interfacial mechanics, the domain geometry, and the domain statistics, thus linking all three fields of study. This transition persists for all cell size distributions, but its exact position is crucially dependent on fluctuations in the parameter values of the functional (quenched disorder). The magnitude of fluctuations can be matched to the observed shape distribution of cells, so that visual observation of cell shapes and statistics provides information about the mechanical state of the tissue. Comparing with experimental data from the Cucumis epidermis, we find that the system is located right at the transition, allowing the tissue to relieve most of the local stress while maintaining integrity. PMID- 26264284 TI - Design of symmetric TIM barrel proteins from first principles. AB - BACKGROUND: Computational protein design is a rapidly maturing field within structural biology, with the goal of designing proteins with custom structures and functions. Such proteins could find widespread medical and industrial applications. Here, we have adapted algorithms from the Rosetta software suite to design much larger proteins, based on ideal geometric and topological criteria. Furthermore, we have developed techniques to incorporate symmetry into designed structures. For our first design attempt, we targeted the (alpha/beta)8 TIM barrel scaffold. We gained novel insights into TIM barrel folding mechanisms from studying natural TIM barrel structures, and from analyzing previous TIM barrel design attempts. METHODS: Computational protein design and analysis was performed using the Rosetta software suite and custom scripts. Genes encoding all designed proteins were synthesized and cloned on the pET20-b vector. Standard circular dichroism and gel chromatographic experiments were performed to determine protein biophysical characteristics. 1D NMR and 2D HSQC experiments were performed to determine protein structural characteristics. RESULTS: Extensive protein design simulations coupled with ab initio modeling yielded several all-atom models of ideal, 4-fold symmetric TIM barrels. Four such models were experimentally characterized. The best designed structure (Symmetrin-1) contained a polar, histidine-rich pore, forming an extensive hydrogen bonding network. Symmetrin-1 was easily expressed and readily soluble. It showed circular dichroism spectra characteristic of well-folded alpha/beta proteins. Temperature melting experiments revealed cooperative and reversible unfolding, with a Tm of 44 degrees C and a Gibbs free energy of unfolding (DeltaG degrees ) of 8.0 kJ/mol. Urea denaturing experiments confirmed these observations, revealing a Cm of 1.6 M and a DeltaG degrees of 8.3 kJ/mol. Symmetrin-1 adopted a monomeric conformation, with an apparent molecular weight of 32.12 kDa, and displayed well resolved 1D-NMR spectra. However, the HSQC spectrum revealed somewhat molten characteristics. CONCLUSIONS: Despite the detection of molten characteristics, the creation of a soluble, cooperatively folding protein represents an advancement over previous attempts at TIM barrel design. Strategies to further improve Symmetrin-1 are elaborated. Our techniques may be used to create other large, internally symmetric proteins. PMID- 26264287 TI - How to estimate solid-electrolyte-interphase features when screening electrolyte materials. AB - Computational screening of battery electrolyte components is an extremely challenging task because very complex features like solid-electrolyte-interphase (SEI) formation and graphite exfoliation need to be taken into account at least in the final screening stage. We present estimators for both SEI formation and graphite exfoliation based on a combinatorial approach using quantum chemistry calculations on model system reactions, which can be applied automatically for a large number of compounds and thus allows for the systematic first assessment of the relevant properties using screening approaches. The thermodynamic effects are assessed using quantum mechanical calculations, while a more heuristic approach is used to estimate the kinetic effects. PMID- 26264288 TI - Identifying representative muscle synergies in overhead football throws. PMID- 26264289 TI - Generic emergence of classical features in quantum Darwinism. AB - Quantum Darwinism posits that only specific information about a quantum system that is redundantly proliferated to many parts of its environment becomes accessible and objective, leading to the emergence of classical reality. However, it is not clear under what conditions this mechanism holds true. Here we prove that the emergence of classical features along the lines of quantum Darwinism is a general feature of any quantum dynamics: observers who acquire information indirectly through the environment have effective access at most to classical information about one and the same measurement of the quantum system. Our analysis does not rely on a strict conceptual splitting between a system-of interest and its environment, and allows one to interpret any system as part of the environment of any other system. Finally, our approach leads to a full operational characterization of quantum discord in terms of local redistribution of correlations. PMID- 26264290 TI - Effect of bridgehead substitution in the Grob fragmentation of norbornyl ketones: a new route to substituted halophenols. AB - Grob fragmentation of suitably designed bicyclic species often generates novel organic skeletons in a facile manner. Herein, we report a comprehensive account of an effective acid-catalyzed Grob fragmentation of trihalonorbornyl ketones to dihalophenol derivatives in good yields. The transformation entails tri-n butyltin hydride (TBTH) mediated regioselective reduction of one of the two bridgehead halogens of readily available Diels-Alder adducts resulting from 1,2,3,4-tetrahalo-5,5-dimethoxycyclopentadiene and vinyl acetate derivatives, followed by its conversion to substituted halophenol species via a three-step hydrolysis-oxidation-rearrangement/aromatization strategy. Both alkyl and aryl substituted norbornyl ketones were studied. A detailed mechanistic analysis employing an isotope labeling experiment revealed plausible mechanistic pathways. Among the two bridgehead substituents, when halogen (X = Cl, Br) stays at C-1 and hydrogen (H, or deuterium, D) at C-4, then product formation takes place via exclusive protonation (supplied by an external acid) at beta carbon (i.e. C-1) of a dienol moiety formed in situ during the Grob-fragmentation, followed by the removal of acidic 4-H (or 4-D) and halide ion (X(-)) from the resulting cyclohexenone intermediate prior to nucleophilic attack on the oxocarbenium ion by X(-) and final enolisation of cyclohexadienone species. A sharp deviation was observed with the regioisomeric bicyclic ketone, wherein the 4-X triggers a facile removal of X(-) and forms the end products without necessitating the involvement of the C-1 substituent (i.e. 1-H/D), thereby retaining it in the final halophenols. It clearly demonstrates how the bridgehead substituents in the two regioisomeric trihalo-norbornyl ketones steer the bicyclic systems to follow entirely different reaction pathways thus suggesting their crucial yet distinct roles in the overall reaction. The present transformation thus manifests the relevance of bridgehead substituents in the Grob fragmentation of such norbornyl systems. Our current strategy also allows one to access ortho-deuterated halophenol compounds. PMID- 26264292 TI - When a student speaks, managers should listen. PMID- 26264293 TI - GBBO is the icing on the cake for baker Alvin. PMID- 26264291 TI - Cannabis use frequency and use-related impairment among African-American and White users: the impact of cannabis use motives. AB - OBJECTIVES: Cannabis use motives are differentially related to cannabis-related impairment and coping motives appear to have the strongest relation to use related impairment. However, it is currently unknown whether African-American individuals differ from White persons in reasons for using cannabis. It is also unknown whether motives' relations to cannabis use and related impairment vary as a function of race. The present study examined the role of race on cannabis use motives and tested whether motives' relations with cannabis use and related impairment differed by race. DESIGN: The sample consisted of 111 (67.6% non Hispanic White, 32.4% African-American) current cannabis-using adults. RESULTS: African-American participants did not significantly differ from White participants on cannabis use frequency or use-related impairment. African American participants endorsed more social motives than White participants. Race interacted with social, coping, and conformity motives to predict cannabis related impairment such that these motives were positively related to cannabis impairment among African-American, but not White, participants. CONCLUSION: Although African-American and White participants do not differ in their cannabis use frequency or cannabis-related impairment, they appear to use cannabis for different reasons. Further, conformity, coping, and social motives were differentially associated with cannabis-related impairment as a function of race. Findings suggest motives for cannabis use should be contexualised in the context of race. PMID- 26264294 TI - Trusts must not let financial woes threaten safe staffing, RCN warns. PMID- 26264295 TI - 'Piecemeal' regulation needs overhaul, says PSA. PMID- 26264296 TI - RCN wins weekend rates and overtime payments for private firm employees. PMID- 26264297 TI - College general secretary wants to meet members. PMID- 26264299 TI - Tram named in nurse's honour. PMID- 26264298 TI - Calais migrant camp conditions are desperate, says nurse volunteer. PMID- 26264301 TI - Legislation aims to ensure staff are fluent in English. PMID- 26264300 TI - Alert over health visitor workloads. PMID- 26264303 TI - Nurse specialist leads the way. PMID- 26264304 TI - Music played during operations can impair team communication. PMID- 26264305 TI - Rethink for end of life care aims to put people before process. PMID- 26264311 TI - Breast cancer. PMID- 26264312 TI - Better care ahead for infants and parents. PMID- 26264313 TI - Miners' nurse recalls going down the pit. PMID- 26264314 TI - In the front line of risk from violence. PMID- 26264322 TI - Saving Lives. PMID- 26264325 TI - Sleep Diary. PMID- 26264327 TI - Accentuate good end of life care but don't side-step the bad. PMID- 26264328 TI - Nurses are being driven to work abroad yet no one seems to care. PMID- 26264329 TI - Gove attack highlights why we urgently need to defend our NHS. PMID- 26264330 TI - Issues relating to disseminating nursing research are unchanged. PMID- 26264332 TI - Help the QNI identify common barriers to effective discharge. PMID- 26264335 TI - Prone positioning in acute respiratory distress syndrome. AB - Acute respiratory distress syndrome (ARDS) is a condition with a high morbidity and mortality rate, and treatment is often long and costly. Prone positioning is a rarely used intervention for patients with this syndrome, although research suggests it may be effective. A literature search was undertaken to examine the effects of prone positioning on oxygenation, morbidity and mortality in patients with ARDS. It revealed that prone positioning, when used with low tidal volume ventilation over an extended period, may reduce mortality rates in selected patients with severe ARDS. The selection of patients with severe ARDS for prone positioning should be done on a case-by-case basis to maximise benefits and minimise complications. Further research is required on the use of prone positioning in patients with severe ARDS to support or disclaim the therapy's use in practice, and to compare confounding variables such as ideal prone duration and mechanical versus manual pronation. PMID- 26264336 TI - Type 1 diabetes and alcohol consumption. AB - Type 1 diabetes is a challenging and complex disorder to manage, and this becomes more difficult when young people are beginning to experience the pleasures and effects of alcohol consumption. For a young person with type 1 diabetes, alcohol consumption can have harmful effects on their current and future wellbeing. The article focuses on the effects of alcohol in type 1 diabetes and the difficulties a young person faces in maintaining glycaemic control when drinking alcohol. The effects of living in an alcohol permissive culture and the knowledge and risks of alcohol consumption, as well as issues associated with depression and denial are discussed. In addition, we aim to raise awareness of best practice guidelines for healthcare professionals to reduce short and long-term complications associated with alcohol-induced hypoglycaemia. PMID- 26264337 TI - Integrating the 6Cs of nursing into mentorship practice. AB - Nurses and midwives are asked to demonstrate the 6Cs (care, compassion, competence, communication, courage and commitment) of nursing in 'everything we do'. Mentors have a crucial role in the provision of health care and in educating nurses and midwives. This article aims to provide guidance to mentors on how to integrate the 6Cs into their mentorship practice, when mentoring pre-registration nursing and midwifery students. It emphasises the importance for mentors of role modelling in relation to the 6Cs. Addressing each of the 6Cs in turn, the article outlines strategies that may be used in mentorship practice to endorse the 6Cs with pre-registration students. The article concludes by considering the mentor's role in robust assessment of the 6Cs. PMID- 26264338 TI - Communication skills. PMID- 26264339 TI - Tips for preceptorship. PMID- 26264341 TI - Care home role needs direction. PMID- 26264342 TI - Caring beyond the bedside. PMID- 26264343 TI - Apply a critical eye to statistics in research. PMID- 26264344 TI - Cancer-type Organic Anion Transporting Polypeptide 1B3: Current Knowledge of the Gene Structure, Expression Profile, Functional Implications and Future Perspectives. AB - Human organic anion transporting polypeptide 1B3 (OATP1B3) is a hepatocyte drug transporter that facilitates uptake of various therapeutic drugs from the circulatory system. Shortly after its initial identification in the liver, OATP1B3 expression was also reported in various solid cancer tissues. In the years since that time, it has been presumed that the OATP1B3 expressed in cancer tissues is identical to that expressed in the liver. However, we have recently identified a new OATP1B3 mRNA variant in cancer tissues, which we have named cancer-type OATP1B3 (Ct-OATP1B3). Given that the identification of Ct-OAT1B3 as a bona fide cancer-associated isoform revises a longstanding study premise, it is essential to fully elucidate the molecular function of Ct-OATP1B3 in cancer cells. Based on the predicted Ct-OATP1B3 protein structure, it is reasonable to assume that it functions as a transporter, but there are a number of ongoing arguments regarding Ct-OATP1B3 protein expression and its functions. With the above points in mind, this review will summarize current knowledge of Ct-OATP1B3 mRNA expression features in cancer tissues and its proposed, yet currently controversial, functions. Based on that background, our future perspectives related to Ct-OATP1B3 studies will also be presented. PMID- 26264345 TI - Novel Lipid and Polymeric Materials as Delivery Systems for Nucleic Acid Based Drugs. AB - Nucleic acid based drugs (NADBs) are short DNA/RNA molecules that include among others, antisense oligonucleotides, aptamers, small interfering RNAs and micro interfering RNAs. Despite the different mechanisms of actions, NABDs have the ability to combat the effects of pathological gene expression in many experimental systems. Thus, nowadays, NABDs are considered to have a great therapeutic potential, possibly superior to that of available drugs. Unfortunately, however, the lack of effective delivery systems limits the practical use of NABDs. Due to their hydrophilic nature, NABDs cannot efficiently cross cellular membrane; in addition, they are subjected to fast degradation by cellular and extracellular nucleases. Together these aspects make the delivery of NABDs as naked molecules almost un-effective. To optimize NABD delivery, several solutions have been investigated. From the first attempts described in the beginning of the 1980s, a burst in the number of published papers occurred in the beginning of 1990 s reaching a peak in 2012-13. The extensive amount of work performed so far clearly witnesses the interest of the scientific community in this topic. In the present review, we will concentrate on the description of the most interesting advances in the field. Particular emphasis will be put on polymeric and lipid materials used alone or in combination with a promising delivery strategy based on the use of carbon nanotubes. The data presented suggest that, although further improvements are required, we are not far from the identification of effective delivery systems for NABDs thus making the clinical use of these molecules closer to reality. PMID- 26264346 TI - Current Strategies to Overcome Resistance to ALK-Inhibitor Agents. AB - The rearrangements of the anaplastic lymphoma kinase (ALK) gene are key drivers in the carcinogenesis of a portion of anaplastic large cell lymphomas (ALCL) and non-small cell lung cancers (NSCLC). Crizotinib, an orally available small molecule, has been the first ALK inhibitor to demonstrate a significant clinical activity in patients with ALK-positive tumors and, thus, to achieve the US food and drug administration approval for the treatment of advanced NSCLC harboring ALK-rearrangements. However, despite initially dramatic and quite durable responses in most cases, acquired resistance to crizotinib arises unavoidably often within the first year of treatment. Three main mechanisms of resistance to crizotinib have been identified to date: mutations in the ALK kinase domain, amplifications of ALK gene, and activation of escape signaling pathways. As ALK signaling dependence is retained in most cases become refractory to crizotinib, newer and more potent ALK-inhibitors have been developed and tested in clinical trials with encouraging activity results. Ceritinib has been recently approved by FDA for the treatment of locally advanced and metastatic NSCLC, and several more agents, including alectinib, ASP3026, and X396, are in active clinical development, demonstrating to be safe, selective and potent. Dual inhibition approaches targeting both ALK and the escape pathways bypassing ALK are currently under investigation. Moreover, being ALK a partner of the heat shock protein Hsp90, inhibitors of this chaperone have been proposed as potential alternative therapeutic strategies for ALKdriven tumors. PMID- 26264347 TI - Functional Brain Imaging Reveals Rapid Blockade of Abdominal Pain Response Upon Anti-TNF Therapy in Crohn's Disease. PMID- 26264348 TI - Index-based dietary patterns and risk of lung cancer in the NIH-AARP diet and health study. AB - BACKGROUND/OBJECTIVES: Dietary pattern analysis considers combinations of food intake and may offer a better measure to assess diet-cancer associations than examining individual foods or nutrients. Although tobacco exposure is the major risk factor for lung cancer, few studies have examined whether dietary patterns, based on preexisting dietary guidelines, influence lung cancer risk. After controlling for smoking, we examined associations between four diet quality indices-Healthy Eating Index-2010 (HEI-2010), Alternate Healthy Eating Index-2010 (AHEI-2010), alternate Mediterranean Diet score (aMED) and Dietary Approaches to Stop Hypertension (DASH)-and lung cancer risk in the NIH-AARP (National Institutes of Health-American Association of Retired Persons) Diet and Health study. SUBJECTS/METHODS: Baseline dietary intake was assessed in 460 770 participants. Over a median of 10.5 years of follow-up, 9272 incident lung cancer cases occurred. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and confidence intervals (CIs). RESULTS: Comparing highest to lowest quintiles, HRs (95% CIs) for lung cancer were as follows: HEI-2010=0.83 (0.77 0.89), AHEI-2010=0.86 (0.80-0.92), aMED=0.85 (0.79-0.91) and DASH=0.84 (0.78 0.90). Among the individual components of the dietary indices, higher consumption of whole grains and fruits was significantly inversely associated with lung cancer risk for several of the diet indices. Total index score analyses stratified by smoking status showed inverse associations with lung cancer for former smokers; however, only HEI-2010 was inversely associated in current smokers and no index score was inversely associated among never smokers. CONCLUSIONS: Although smoking is the factor most strongly associated with lung cancer, this study adds to a growing body of evidence that diet may have a modest role in reducing lung cancer risk, especially among former smokers. PMID- 26264349 TI - Serum 25-hydroxyvitamin D and self-reported mental health status in adult Danes. AB - BACKGROUND/OBJECTIVES: Vitamin D receptors and vitamin D-metabolising enzymes are present in the brain and in the central nervous system at sites responsible for the regulation of emotions and behaviour. This raises the hypothesis that low vitamin D is related to poor mental health. Our aim was to examine the association between serum 25-hydroxyvitamin D (25(OH)D) and the self-reported symptoms and diagnosis of depression and anxiety in the adult general population. SUBJECTS/METHODS: Serum 25(OH)D was measured in three Danish population-based studies, including 5308 adults aged 18-64 years. After 5 years, 2004 participants were re-examined. Symptoms of depression and anxiety were assessed by the Symptom Check List (SCL)-90-R, and self-reported doctor-diagnosed depression and anxiety was recorded by using a questionnaire. RESULTS: Serum 25(OH)D was not associated with SCL average scores for depression and anxiety when analysed by quantile median regression adjusted for sex, age and other potential confounders. The beta coefficient and 95% confidence interval (CI) per 10 nmol/l serum 25(OH)D were 0.00 (-0.00 to 0.01) and P=0.23 for depression and -0.00 (-0.01 to 0.00) and P=0.19 for anxiety. Furthermore, no evidence of an association was observed with longitudinal changes (combining depression and anxiety score: beta (95% CI)=0.00 (-0.00 to 0.00), P=0.90), with scores >90 percentiles (odds ratio (OR) (95% CI)=1.02 (0.98-1.07), P=0.32), or with self-reported history (OR (95% CI)=1.02 (0.97-1.07), P=0.47) or incidence (OR (95% CI)=1.02 (0.92-1.12), P=0.77) of doctor-diagnosed depression and/or anxiety. CONCLUSIONS: Our results suggest that low serum 25(OH)D is not associated with self-reported symptoms/diagnosis of depression and anxiety. PMID- 26264350 TI - Eating behaviour and weight status at 2 years of age: data from the Cork BASELINE Birth Cohort Study. AB - BACKGROUND/OBJECTIVES: To conduct an analysis of associations between eating behaviours and weight status in 2-year-old children. SUBJECTS/METHODS: Data were collected prospectively in the maternal-infant dyad Cork BASELINE Birth Cohort Study. The weight status of children aged 2 years (n=1189) was assigned using the International Obesity Task Force BMI cutoffs using measured heights and weights. Eating behaviours were assessed using the Children's Eating Behaviour Questionnaire (CEBQ). RESULTS: Eighty percent of children were of normal weight, 14% were overweight or obese and 6% were underweight. From the CEBQ, food approach behaviours including Enjoyment of Food (odds ratio (OR)=1.90, 95% confidence interval (CI)=1.46-2.48) and Food Responsiveness (OR=1.73, 95% CI=1.47 2.03) were associated with overweight/obesity (all P<0.001). The food avoidant behaviours of Satiety Responsiveness (OR=2.03, 95% CI=1.38-2.98) and Slowness in Eating (OR=1.44, 95% CI=1.01-2.04) were associated with underweight at 2 years (all P<0.05). CONCLUSIONS: Eating behaviours are associated with weight status as early as 2 years of age. PMID- 26264351 TI - Narrative review of models and success factors for scaling up public health interventions. AB - BACKGROUND: To maximise the impact of public health research, research interventions found to be effective in improving health need to be scaled up and delivered on a population-wide basis. Theoretical frameworks and approaches are useful for describing and understanding how effective interventions are scaled up from small trials into broader policy and practice and can be used as a tool to facilitate effective scale-up. The purpose of this literature review was to synthesise evidence on scaling up public health interventions into population wide policy and practice, with a focus on the defining and describing frameworks, processes and methods of scaling up public health initiatives. METHODS: The review involved keyword searches of electronic databases including MEDLINE, CINAHL, PsycINFO, EBM Reviews and Google Scholar between August and December 2013. Keywords included 'scaling up' and 'scalability', while the search terms 'intervention research', 'translational research', 'research dissemination', 'health promotion' and 'public health' were used to focus the search on public health approaches. Studies included in the review were published in English from January 1990 to December 2013 and described processes, theories or frameworks associated with scaling up public health and health promotion interventions. RESULTS: There is a growing body of literature describing frameworks for scaling health interventions, with the review identifying eight frameworks, the majority of which have an explicit focus on scaling up health action in low and middle income country contexts. Key success factors for scaling up included the importance of establishing monitoring and evaluation systems, costing and economic modelling of intervention approaches, active engagement of a range of implementers and the target community, tailoring the scaled-up approach to the local context, the use of participatory approaches, the systematic use of evidence, infrastructure to support implementation, strong leadership and champions, political will, well defined scale-up strategy and strong advocacy. CONCLUSIONS: Effective scaling up requires the systematic use of evidence, and it is essential that data from implementation monitoring is linked to decision making throughout the scaling up process. Conceptual frameworks can assist both policy makers and researchers to determine the type of research that is most useful at different stages of scaling up processes. PMID- 26264352 TI - The Notch pathway in colorectal cancer. AB - Colorectal cancer (CRC) is the third leading cause of cancer death worldwide. It is also the third most common cancer diagnosis among men, and the second most common cancer diagnosis among women. Globally, CRC can account for nearly 694,000 annual deaths. It is widely appreciated that CRC is the result of dysregulated cellular pathways that promote an inappropriate stem-cell-like phenotype, apoptotic resistance, unchecked proliferation and metastatic spread. While no single pathway is responsible for all of these attributes, an array of recent studies suggests a pivotal role for abnormal Notch-1 signaling in CRC, in part due to interconnectivity of Notch with other pathways. This review will summarize recent evidence for a role of Notch signaling in CRC, will consider interconnectivity between Notch and other pathways involved in CRC and will discuss the possible utility of targeting Notch as a CRC therapeutic. PMID- 26264353 TI - Impact of smoking on neurodegeneration and cerebrovascular disease markers in cognitively normal men. AB - BACKGROUND AND PURPOSE: Smoking is a major risk factor for cognitive decline and dementia. However, the exact pathobiology of smoking remains unknown. The effects of smoking on cortical thickness as a biomarker of neurodegeneration or white matter hyperintensities and lacunes as biomarkers of cerebrovascular burden were concurrently evaluated. METHODS: Our study included 977 cognitively normal men who visited a health promotion centre and underwent medical check-ups, including 3.0 T magnetic resonance imaging. Participants were categorized into never smoker, past smoker or current smoker groups and pack-years and the years of smoking cessation were used as continuous variables. RESULTS: The current smoker group exhibited cortical thinning in frontal and temporo-parietal regions compared with the never smoker group. These effects were particularly prominent in smokers with a high cumulative exposure to smoking in the current smoker group. However, there was no association between smoking and the severity of white matter hyperintensity or number of lacunes. CONCLUSION: Our findings indicate that smoking might impact on neurodegeneration rather than cerebrovascular burdens in cognitively normal men, suggesting that smoking might be an important modifiable risk factor for the development of Alzheimer's disease. PMID- 26264355 TI - Ethyl-Zinc(II)-Cation Equivalents: Synthesis and Hydroamination Catalysis. AB - Ion-like ethylzinc(II) compounds with weakly coordinating aluminates [Al(OR(F))4](-) and [(R(F)O)3Al-F-Al(OR(F))3](-) (R(F)=C(CF3)3) were synthesized in a one-pot reaction and fully characterized by single-crystal X-ray diffraction, NMR and vibrational spectroscopy, and by quantum chemical calculations. The catalytic activity of ion-like Et-Zn[Al(OR(F))4] in intermolecular hydroamination and in the unusual double hydroamination of anilines and alkynes was investigated. Favorable performance was also found in comparison to the Et2Zn/[PhNMe2H](+)[B(C6F5)4](-) system generated in situ at lower catalyst loadings of 2.5 mol %. PMID- 26264354 TI - Effects of nitrogen fertilisation rate and maturity of grass silage on methane emission by lactating dairy cows. AB - Grass silage is typically fed to dairy cows in temperate regions. However, in vivo information on methane (CH(4)) emission from grass silage of varying quality is limited. We evaluated the effect of two rates of nitrogen (N) fertilisation of grassland (low fertilisation (LF), 65 kg of N/ha; and high fertilisation (HF), 150 kg of N/ha) and of three stages of maturity of grass at cutting: early maturity (EM; 28 days of regrowth), mid maturity (MM; 41 days of regrowth) and late maturity (LM; 62 days of regrowth) on CH(4) production by lactating dairy cows. In a randomised block design, 54 lactating Holstein-Friesian dairy cows (168+/-11 days in milk; mean+/-standard error of mean) received grass silage (mainly ryegrass) and compound feed at 80 : 20 on dry matter basis. Cows were adapted to the diet for 12 days and CH(4) production was measured in climate respiration chambers for 5 days. Dry matter intake (DMI; 14.9+/-0.56 kg/day) decreased with increasing N fertilisation and grass maturity. Production of fat- and protein-corrected milk (FPCM; 24.0+/-1.57 kg/day) decreased with advancing grass maturity but was not affected by N fertilisation. Apparent total-tract feed digestibility decreased with advancing grass maturity but was unaffected by N fertilisation except for an increase and decrease in N and fat digestibility with increasing N fertilisation, respectively. Total CH(4) production per cow (347+/ 13.6 g/day) decreased with increasing N fertilisation by 4% and grass maturity by 6%. The smaller CH(4) production with advancing grass maturity was offset by a smaller FPCM and lower feed digestibility. As a result, with advancing grass maturity CH(4) emission intensity increased per units of FPCM (15.0+/-1.00 g CH(4)/kg) by 31% and digestible organic matter intake (33.1+/-0.78 g CH(4)/kg) by 15%. In addition, emission intensity increased per units of DMI (23.5+/-0.43 g CH(4)/kg) by 7% and gross energy intake (7.0+/-0.14% CH(4)) by 9%, implying an increased loss of dietary energy with advancing grass maturity. Rate of N fertilisation had no effect on CH(4) emissions per units of FPCM, DMI and gross energy intake. These results suggest that despite a lower absolute daily CH(4) production with a higher N fertilisation rate, CH(4) emission intensity remains unchanged. A significant reduction of CH(4) emission intensity can be achieved by feeding dairy cows silage of grass harvested at an earlier stage of maturity. PMID- 26264357 TI - National Hispanic Heritage Month. PMID- 26264356 TI - The common PNPLA3 variant p.I148M is associated with liver fat contents as quantified by controlled attenuation parameter (CAP). AB - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is becoming the most prevalent liver disorder. The PNPLA3 (adiponutrin) variant p.I148M has been identified as common genetic modifier of NAFLD. Our aim was to assess the relationships between genetic risk and non-invasively measured liver fat content. METHODS: Hepatic steatosis was quantified by transient elastography, using the controlled attenuation parameter (CAP) in 174 patients with chronic liver diseases (50% women, age 18-77 years). In addition, a cohort of 174 gender matched healthy controls (50% women, age 32-77 years) was recruited. The PNPLA3 mutation as well as the novel NAFLD-predisposing genetic variant (TM6SF2 p.E167K) were genotyped with allele-specific probes. RESULTS: The PNPLA3 genotype correlated significantly (P = 0.001) with hepatic CAP measurements. The p.148M risk allele increased the odds of developing liver steatosis (OR = 2.39, P = 0.023). In multivariate models, BMI and PNPLA3 mutation were both independently associated with CAP values (P < 0.001 and P = 0.007, respectively). Carriers of the TM6SF2 risk allele presented with increased aminotransferase activities (ALT: P = 0.007, AST: P = 0.004), but the presence of this variant did not affect CAP values. CONCLUSIONS: The PNPLA3 p.I148M variant represents the most important prosteatotic genetic risk factor. NAFLD carriers of this variant should be followed up carefully, with elastography and CAP being ideally suited for this purpose. PMID- 26264358 TI - President's Message: There IS an "I" in Team. PMID- 26264359 TI - Systematic review with meta-analysis: faecal diversion for management of perianal Crohn's disease. AB - BACKGROUND: Temporary faecal diversion is sometimes used for management of refractory perianal Crohn's disease (CD) with variable success. AIMS: To perform a systematic review with meta-analysis to evaluate the effectiveness, long-term outcomes and factors associated with success of temporary faecal diversion for perianal CD. METHODS: Through a systematic literature review through 15 July 2015, we identified 16 cohort studies (556 patients) reporting outcomes after temporary faecal diversion. We estimated pooled rates [with 95% confidence interval (CI)] of early clinical response, attempted and successful restoration of bowel continuity after temporary faecal diversion (without symptomatic relapse), and rates of re-diversion (in patients with attempted restoration) and proctectomy (with or without colectomy and end-ileostomy). We identified factors associated with successful restoration of bowel continuity. RESULTS: On meta analysis, 63.8% (95% CI: 54.1-72.5) of patients had early clinical response after faecal diversion for refractory perianal CD. Restoration of bowel continuity was attempted in 34.5% (95% CI: 27.0-42.8) of patients, and was successful in only 16.6% (95% CI: 11.8-22.9). Of those in whom restoration was attempted, 26.5% (95% CI: 14.1-44.2) required re-diversion because of severe relapse. Overall, 41.6% (95% CI: 32.6-51.2) of patients required proctectomy after failure of temporary faecal diversion. There was no difference in the successful restoration of bowel continuity after temporary faecal diversion in the pre-biological or biological era (13.7% vs. 17.6%, P = 0.60), in part due to selection bias. Absence of rectal involvement was the most consistent factor associated with restoration of bowel continuity. CONCLUSIONS: Temporary faecal diversion may improve symptoms in approximately two-thirds of patients with refractory perianal Crohn's disease, but bowel restoration is successful in only 17% of patients. PMID- 26264360 TI - Significant Variation in Blood Transfusion Practice Persists following Upper GI Cancer Resection. AB - PURPOSE: Perioperative blood transfusions are costly and linked to adverse clinical outcomes. We investigated the factors associated with variation in blood transfusion utilization following upper gastrointestinal cancer resection and its association with infectious complications. METHODS: The Statewide Planning and Research Cooperative System was queried for elective esophagectomy, gastrectomy, and pancreatectomy for malignancy in NY State from 2001 to 2013. Bivariate and hierarchical logistic regression analyses were performed to assess the factors associated with receiving a perioperative allogeneic red blood cell transfusion. Additional multivariable analysis examined the relationship between transfusion and infectious complications. RESULTS: Among 14,875 patients who underwent upper GI cancer resection, 32 % of patients received a perioperative blood transfusion. After controlling for patient, surgeon, and hospital-level factors, significant variation in transfusion rates was present across both surgeons (p < 0.0001) and hospitals (p < 0.0001). Receipt of a blood transfusion was also independently associated with wound infection (OR = 1.68, 95% CI = 1.47 and 1.91), pneumonia (OR = 1.98, 95% CI = 1.74 and 2.26), and sepsis (OR = 2.49, 95% CI = 2.11 and 2.94). CONCLUSION: Significant variation in perioperative blood transfusion utilization is present at both the surgeon and hospital level. These findings are unexplained by patient-level factors and other known hospital characteristics, suggesting that variation is due to provider preferences and/or lack of standardized transfusion protocols. Implementing institutional transfusion guidelines is necessary to limit unwarranted variation and reduce infectious complication rates. PMID- 26264361 TI - Penetrating Disease, Narcotic Use, and Loop Ostomy Are Associated with Ostomy and IBD-related Complications After Ostomy Surgery in Crohn's Disease Patients. AB - BACKGROUND: For medically refractory or obstructive Crohn's disease (CD), ostomy surgery remains an important therapeutic option. Outcomes and complications of this approach have not been well described in the era of biological therapies. Our study aims to characterize CD patients undergoing ostomy creation and assess outcome predictors. METHODS: We performed a retrospective chart review of CD patients who underwent ostomy creation in our center from 2011 to 2014. Data collected include patient demographics, detailed disease- and surgery-related variables, and clinical outcomes after 26 weeks of follow-up. RESULTS: Of the 112 patients, 54 % were female, the median age was 39 years (range 19-78), the median disease duration was 13 years (range 0-50), 54 % had ileo-colonic disease, 55 % had stricturing phenotype, and 59 % had perianal disease. Sixty-two percent received end ostomies, and 38 % received loop ostomies. The leading indications for surgery were stricturing, fistulizing, and perianal disease (35 %). Forty three (38 %) patients had 76 major complications, including dehydration (22 cases), intra-abdominal infection (16), and obstruction (14). Increased major postoperative complications correlated with penetrating disease (p = 0.02, odds ratio [OR] = 5.52, 95 % confidence interval [CI] = 1.25-24.42), the use of narcotics before surgery (p = 0.04, OR = 2.54, 95 % CI = 1.02-6.34), and loop ostomies (p = 0.004, OR = 4.2, 95 % CI = 1.57-11.23). CONCLUSIONS: Penetrating phenotype, the use of narcotics before surgery, and loop ostomies are associated with major complications in CD patients undergoing ostomy creation. These findings may influence risk management of CD patients needing ostomies. PMID- 26264362 TI - Acute Cholecystitis-Optimal Timing for Early Cholecystectomy: a French Nationwide Study. AB - BACKGROUND: The recommended treatment for acute calculous cholecystitis combines antibiotics and cholecystectomy. To reduce morbidity and mortality, guidelines recommend early cholecystectomy. However, the optimal timing for surgery on first admission remains controversial. This study aims to determine the best timing for cholecystectomy in patients presenting with acute calculous cholecystitis. STUDY DESIGN: The French national health-care database was analyzed to identify all patients undergoing cholecystectomy for acute cholecystitis during the same hospital stay between January 2010 and December 2013. Data regarding patients, procedures, and hospitals characteristics were collected. The relationship between surgery's timing and clinical outcome was evaluated by multiple logistic regressions. RESULTS: Overall, 42,452 patients from 507 hospitals were included in the study. Postoperative complications requiring invasive treatment occurred in 961 patients (2.3 %), and the mortality rate was 1.1 %. Adverse postoperative outcomes-intensive care admission, reoperation, and postoperative sepsis-were significantly lower when surgery was performed between days 1 and 3 (3-3.3, 0.5 0.6, and 3.8-4.1 %, respectively) when compared to surgery performed on the day of admission (5.6, 1.2, and 5.2 %, p < 0.001) or from day 5 onward (4.5, 1, and 6.5 %, respectively; p < 0.001). Mortality was also significantly lower in patients undergoing cholecystectomy between days 1 and 3 after admission (0.8-1 %) when compared to patients operated on the day of admission or after day 3 (1.4 % on day 0, 1.2 % on day 4, and 1.9 % from day 5: all p < 0.001). CONCLUSION: For patients with acute calculous cholecystitis, all efforts should be made to perform cholecystectomy within 3 days after hospital admission in order to decrease morbidity and mortality. PMID- 26264363 TI - Duct-to-Mucosa Versus Invagination Pancreaticojejunostomy Following Pancreaticoduodenectomy: a Systematic Review and Meta-Analysis. AB - BACKGROUND: Postoperative pancreatic fistula (POPF) is one of the most common complications after pancreaticoduodenectomy (PD). The ideal choice of pancreaticojejunostomy (PJ) anastomosis remains a matter of debate. METHODS: A meta-analysis of randomized controlled trials (RCTs) comparing duct-to-mucosa with invagination PJ following PD was performed. Pooled odds ratio (OR) with 95 % confidence intervals (CI) were calculated using fixed-effects or random-effects models. RESULTS: In total, five RCTs involving 654 patients were included. Meta analysis revealed no significant difference in POPF rate between the duct-to mucosa and invagination PJ techniques (OR = 1.23, 95 % CI = 0.78-1.93; P = 0.38). Two of five trials applied the POPF definition proposed by the International Study Group of Pancreatic Surgery (ISGPS). Using this definition, the incidence of clinically relevant POPF was lower in patients undergoing invagination PJ than in those undergoing duct-to-mucosa PJ (OR = 2.94, 95 % CI = 1.31-6.60; P = 0.009). There was no significant difference in terms of delayed gastric emptying, intra-abdominal collection, overall morbidity and mortality, reoperation rate, and length of hospital stay between the two groups. CONCLUSION: Invagination PJ is not superior to duct-to-mucosa PJ in terms of POPF and other complications but appears to reduce clinically relevant POPF. Further well-designed RCTs that use ISGPS definition are still required before strong evidence-based recommendations can be formulated. PMID- 26264364 TI - A prospective evaluation on external jugular vein cut-down approach for TIVAD implantation. AB - BACKGROUND: Totally implantable venous access devices can be implanted both by percutaneous approaches and by surgical approaches with cephalic vein or external jugular vein cut-down techniques that are related to low intraoperative complication rates. The authors report a prospective evaluation of 83 consecutive external jugular vein cut-down approaches for totally implantable venous access devices implantation. METHODS: Eighty three consecutive patients (28 M, 55 F, mean age 54.2) suffering from solid tumors (58) or hematologic diseases (25) were consecutively submitted to totally implantable venous access devices insertion through external jugular vein cut-down approach (75 on right side, 8 on left side). RESULTS: All devices were surgically implanted; no instances of intraoperative complications were detected. After a minimum follow-up of 150 days, only one case of wound hematoma and one case of device malfunction due to incorrect catheter angulation were noted. Postoperative patient satisfaction was evaluated by the use of specific questionnaire that demonstrated a good satisfaction and compliance (92.8%) of patients with implanted devices. CONCLUSIONS: Despite the lack of controlled studies comparing external jugular vein cut-down approach vs other approaches, this approach should be considered as a tool for long-term central vein catheters positioning, both as an alternative and for primary approach. PMID- 26264365 TI - Sensory dysfunction and quality of life after great auricular nerve sacrifice during parotidectomy: our experience. AB - OBJECTIVE: This study aimed to investigate the impact on patients' quality of life of great auricular nerve sacrifice during parotidectomy. METHODS: A retrospective review was conducted of 191 consecutive patients who underwent parotidectomy with great auricular nerve sacrifice between 2006 and 2011. Residual sensory dysfunction and its impact on quality of life was analysed using an eight-item quality of life survey. RESULTS: In all, 139 out of 191 patients (72.8 per cent) experienced one or more abnormal sensations in the ear or neck region after surgery. There was a moderate inverse correlation between the number of abnormal sensations and time elapsed since surgery. Moreover, the degree of discomfort correlated significantly with the frequency of symptom occurrence (p < 0.001), duration of the abnormal sensation (p < 0.001) and size of the affected area (p < 0.001). CONCLUSION: Sacrifice of the great auricular nerve has only a small impact on patient quality of life; their daily activities are not significantly affected. PMID- 26264366 TI - Call for a review of services for people with neurological disorders. PMID- 26264368 TI - A case of Fahr's disease examined by multi-modal imaging. PMID- 26264367 TI - Y-27632 is associated with corticosteroid-potentiated control of pulmonary remodeling and inflammation in guinea pigs with chronic allergic inflammation. AB - BACKGROUND: Previously, we showed that treatment with the Rho-kinase inhibitor Y 27632 was able to control airway responsiveness, inflammation, remodeling, and oxidative stress in an animal model of asthma, suggesting that this drug is beneficial in asthma. However, studies evaluating the effects of these inhibitors in conjunction with corticosteroids on chronic pulmonary inflammation have not been conducted. Therefore, we evaluated the effects of treatment with the Rho kinase inhibitor Y-27632, with or without concurrent dexamethasone treatment, on airway and lung tissue mechanical responses, inflammation, extracellular matrix remodeling, and oxidative stress in guinea pigs with chronic allergic inflammation. METHODS: The guinea pigs were subjected to seven ovalbumin or saline inhalation exposures. Treatment with Y-27632 (1 mM) and dexamethasone (2 mg/kg) started at the fifth inhalation. Seventy-two hours after the seventh inhalation, the pulmonary mechanics were evaluated and exhaled nitric oxide (ENO) levels were determined. The lungs were removed and histological analysis was performed using morphometry. RESULTS: The treatment of guinea pigs with the Rho kinase inhibitor and dexamethasone (ORC group) decreased ENO, the maximal mechanical responses after antigen challenge, inflammation, extracellular matrix remodeling and oxidative stress in the lungs. This therapeutic strategy reduced the levels of collagen and IFN-gamma in the airway walls, as well as IL-2, IFN gamma, 8-iso-PGF2alpha and NF-kappaB in the distal parenchyma, when compared to isolated treatment with corticosteroid or Rho-kinase inhibitor (P < 0.05) and reduced the number of TIMP-1-positive cells and eosinophils in the alveolar septa compared to corticosteroid-treated animals (P < 0.05). The combined treatment with the Rho-kinase inhibitor and the corticosteroid provided maximal control over the remodeling response and inflammation in the airways and parenchyma. CONCLUSIONS: Rho-kinase inhibition, alone or in combination with corticosteroids, can be considered a future pharmacological tool for the control of asthma. PMID- 26264369 TI - Why New Journals? The Growth of the EJNMMI Family. PMID- 26264370 TI - Identification of genes expressed in the migrating primitive myeloid lineage of Xenopus laevis. AB - BACKGROUND: During primitive hematopoiesis in Xenopus, cebpa and spib expressing myeloid cells emerge from the anterior ventral blood island. Primitive myeloid cells migrate throughout the embryo and are critical for immunity, healing, and development. Although definitive hematopoiesis has been studied extensively, molecular mechanisms leading to the migration of primitive myelocytes remain poorly understood. We hypothesized these cells have specific extracellular matrix modifying and cell motility gene expression. RESULTS: In situ hybridization screens of transcripts expressed in Xenopus foregut mesendoderm at stage 23 identified seven genes with restricted expression in primitive myeloid cells: destrin; coronin actin binding protein, 1a; formin-like 1; ADAM metallopeptidase domain 28; cathepsin S; tissue inhibitor of metalloproteinase-1; and protein tyrosine phosphatase nonreceptor 6. A detailed in situ hybridization analysis revealed these genes are initially expressed in the aVBI but become dispersed throughout the embryo as the primitive myeloid cells become migratory, similar to known myeloid markers. Morpholino-mediated loss-of-function and mRNA-mediated gain-of-function studies revealed the identified genes are downstream of Spib.a and Cebpa, key transcriptional regulators of the myeloid lineage. CONCLUSIONS: We have identified genes specifically expressed in migratory primitive myeloid progenitors, providing tools to study how different gene networks operate in these primitive myelocytes during development and immunity. PMID- 26264371 TI - Risk stratification in patients with pulmonary hypertension undergoing transcatheter aortic valve replacement. AB - OBJECTIVE: Pulmonary hypertension (PH) is associated with increased mortality after surgical or transcatheter aortic valve replacement (TAVR) for aortic stenosis (AS), and when the pulmonary artery pressure is particularly elevated, there may be questions about the clinical benefit of TAVR. We aimed to identify clinical and haemodynamic factors associated with increased mortality after TAVR among those with moderate/severe PH. METHODS: Among patients with symptomatic AS at high or prohibitive surgical risk receiving TAVR in the Placement of Aortic Transcatheter Valves (PARTNER) I randomised trial or registry, 2180 patients with an invasive measurement of mean pulmonary artery pressure (mPAP) recorded were included, and moderate/severe PH was defined as an mPAP >=35 mm Hg. RESULTS: Increasing severity of PH was associated with progressively worse 1-year all cause mortality: none (n=785, 18.6%), mild (n=838, 22.7%) and moderate/severe (n=557, 25.0%) (p=0.01). The increased hazard of mortality associated with moderate/severe PH was observed in females, but not males (interaction p=0.03). In adjusted analyses, females with moderate/severe PH had an increased hazard of death at 1 year compared with females without PH (adjusted HR 2.14, 95% CI 1.44 to 3.18), whereas those with mild PH did not. Among males, there was no increased hazard of death associated with any severity of PH. In a multivariable Cox model of patients with moderate/severe PH, oxygen-dependent lung disease, inability to perform a 6 min walk, impaired renal function and lower aortic valve mean gradient were independently associated with increased 1-year mortality (p<0.05 for all), whereas several haemodynamic indices were not. A risk score, including these factors, was able to identify patients with a 15% vs 59% 1-year mortality. CONCLUSIONS: The relationship between moderate/severe PH and increased mortality after TAVR is altered by sex, and clinical factors appear to be more influential in stratifying risk than haemodynamic indices. These findings may have implications for the evaluation of and treatment decisions for patients referred for TAVR with significant PH. TRIAL REGISTRATION: NCT00530894. PMID- 26264372 TI - Complete chloroplast genome sequence of MD-2 pineapple and its comparative analysis among nine other plants from the subclass Commelinidae. AB - BACKGROUND: Pineapple (Ananas comosus var. comosus) is known as the king of fruits for its crown and is the third most important tropical fruit after banana and citrus. The plant, which is indigenous to South America, is the most important species in the Bromeliaceae family and is largely traded for fresh fruit consumption. Here, we report the complete chloroplast sequence of the MD-2 pineapple that was sequenced using the PacBio sequencing technology. RESULTS: In this study, the high error rate of PacBio long sequence reads of A. comosus's total genomic DNA were improved by leveraging on the high accuracy but short Illumina reads for error-correction via the latest error correction module from Novocraft. Error corrected long PacBio reads were assembled by using a single tool to produce a contig representing the pineapple chloroplast genome. The genome of 159,636 bp in length is featured with the conserved quadripartite structure of chloroplast containing a large single copy region (LSC) with a size of 87,482 bp, a small single copy region (SSC) with a size of 18,622 bp and two inverted repeat regions (IRA and IRB) each with the size of 26,766 bp. Overall, the genome contained 117 unique coding regions and 30 were repeated in the IR region with its genes contents, structure and arrangement similar to its sister taxon, Typha latifolia. A total of 35 repeats structure were detected in both the coding and non-coding regions with a majority being tandem repeats. In addition, 205 SSRs were detected in the genome with six protein-coding genes contained more than two SSRs. Comparative chloroplast genomes from the subclass Commelinidae revealed a conservative protein coding gene albeit located in a highly divergence region. Analysis of selection pressure on protein-coding genes using Ka/Ks ratio showed significant positive selection exerted on the rps7 gene of the pineapple chloroplast with P less than 0.05. Phylogenetic analysis confirmed the recent taxonomical relation among the member of commelinids which support the monophyly relationship between Arecales and Dasypogonaceae and between Zingiberales to the Poales, which includes the A. comosus. CONCLUSIONS: The complete sequence of the chloroplast of pineapple provides insights to the divergence of genic chloroplast sequences from the members of the subclass Commelinidae. The complete pineapple chloroplast will serve as a reference for in-depth taxonomical studies in the Bromeliaceae family when more species under the family are sequenced in the future. The genetic sequence information will also make feasible other molecular applications of the pineapple chloroplast for plant genetic improvement. PMID- 26264373 TI - Diversity within the genus Elymus (Poaceae: Triticeae) II: analyses of variation within 5S nrDNA restrict membership in the genus to species with StH genomes. AB - The genus Elymus is a repository for a large number of species that have been difficult to classify by traditional techniques due to their remarkable levels of polymorphism. Following the genome analyses of Yen and Yang (Genus Elymus 5:58 362, 2013), we used sequences of the nr5SDNA to investigate diversity within those 24 species having St and H haplomes (Baum et al. Mol Genet Genomics 290:329 42, 2015) and for which the genome status was known. The present work extends this analysis to include eight species for which there was no information on genomic status. Our results show that these eight have nr5SDNA sequences that can be assigned to unit classes of orthologous sequences found in St and H haplomes, suggesting that the presence of St and H haplomes is characteristic of the genus. We then carried out a set of canonical discriminant analyses based on 247 DNA new sequences from these 8 species plus the 1054 sequences previously identified from 24 Elymus species. Sequences were analyzed to answer the following questions: Do the species integrate or are they different? Are the tetraploids different from the higher-ploid species? Are the species united within sections, or the same within regions? How do the species fare when divided according to sections? The main results of the canonical discriminant analyses are that the species are united within the tetraploids and within the hexaploids, within each region and within each section. In addition, a series of classificatory discriminant analyses showed that the identification tests are different, although not sufficiently useful for the discrimination of all the species. We also demonstrate the power of our approach by showing that the voucher for Elymus mobilis is not Elymus at all, but Leymus. PMID- 26264374 TI - Effects of combined extract of cocoa, coffee, green tea and garcinia on lipid profiles, glycaemic markers and inflammatory responses in hamsters. AB - BACKGROUND: Dyslipidaemia is highly associated with cardiovascular and cerebrovascular diseases, which have been ranked second and third place of leading causes of death in Taiwan. Some plant extracts have been proved effective against dyslipidaemia. However, the combination of plant extracts was rarely studied. The purpose of the present study is to understand the beneficial effects of a combined extract (comprising cocoa, coffee, green tea and garcinia; CCGG) on lipid profiles in serum, liver, and faeces as well as glycaemic markers and related proinflammatory cytokines by using an appropriate animal model, the golden Syrian hamster. METHODS: A total of 40 male hamsters were randomly assigned to five groups: (1) vehicle control, (2) high-cholesterol diet control, (3) high-cholesterol diet of 311 mg/kg/d of CCGG, (4) high-cholesterol diet of 622 mg/kg/d of CCGG and (5) high-cholesterol diet of 1555 mg/kg/d of CCGG. At the end of the experiment, blood, tissue and faecal samples were collected for further analysis. RESULTS: After 6 weeks of treatment, CCGG supplementation significantly reduced serum lipid content (triglycerides, total cholesterol and LDL-C) and hepatic lipid content (triglycerides and cholesterol) with dose dependent effects. In addition, an increase in excretion of faecal lipids (bile acids) was observed after supplementation. Furthermore, the homeostasis model assessment of insulin resistance (HOMA-IR) index and serum proinflammatory cytokine levels (TNF-alpha and IL-6) involved in dyslipidaemia was markedly improved. In addition, by monitoring biochemical parameters as well as histopathology of major tissues, no toxicity was observed after the consumption of CCGG. CONCLUSION: Dietary CCGG supplementation may exert potential effects on ameliorating hyperlipidaemia, insulin resistance, liver steatosis and related inflammation. PMID- 26264375 TI - Ictal Magnetic Source Imaging in Presurgical Assessment. AB - Ictal MEG recordings constitute rare data. The objective of this study was to evaluate ictal magnetic source localization (MSI), using two algorithms: linearly constrained minimum variance (LCMV), a beamforming technique and equivalent current dipole (ECD). Ictal MSI was studied in six patients. Three of them were undergoing post-operative re-evaluation. For all patients, results were validated by the stereoelectroencephalographic (SEEG) definition of the epileptogenic zone (EZ). EZ was quantified using the epileptogenicity index (EI) method, which accounts for both the propensity of a brain area to generate rapid discharges and the time for this area to become involved in the seizure. EI values range from 0 (no epileptogenicity) to 1 (maximal epileptogenicity). Levels of concordance between ictal MSI and EZ were determined as follows: A: ictal MSI localized the site whose value EI = 1, B: MSI localized a part of the EZ (not corresponding to the maximal value of EI = 1), C: a region could be identified on ictal MSI but not on SEEG, D: a region could be identified on SEEG but not on MSI, E: different regions were localized on MSI and SEEG. Ictal MEG pattern consisted of rhythmic activities between 10 and 20 Hz for all patients. For LCMV (first maxima), levels of concordance were A (two cases), B (two cases) and E (two cases). For ECD fitted on each time point separately (location characterized by the best goodness of-fit value), levels of concordance were A (one case), B (one case), D (three cases) and E (one case). For ECD calculated for the whole time window, levels of concordance were A (two cases) and D (four cases). Source localization methods performed on rhythmic patterns can localize the EZ as validated by SEEG. In terms of concordance, LCMV was superior to ECD. In some cases, LCMV allows extraction of several maxima that could reflect ictal dynamics. In a medial temporal lobe epilepsy case, ictal MSI indicated an area of delayed propagation and was non contributory to the presurgical assessment. PMID- 26264376 TI - An Analysis of the Characteristics of Thoracic and Abdominal Injuries Due to Gunshot Homicides in Israel. AB - De-identified wound data from 197 homicidal gunshot postmortems were obtained between 2000 and 2008. Forensic ballistics data were only available for cases between 2004 and 2008. Males represent 91% of gunshot victims and were struck in the thorax/abdomen with an average of 2.3 bullets. The type of firearms involved were semi-automatic pistols in the predominant caliber 9-mm Luger and assault rifles in caliber 5.56 * 45 mm and caliber 7.62 * 39 mm Soviet, using full metal jacket bullets. The majority of shootings occurred at ranges of 1 m or greater. The most common bullet path was front to back in 66% of cases. Entry wounds occurred more often on the left side of the thorax, abdomen, and back. The most common critical organs/tissues to sustain bullet trauma in descending order were as follows: heart, lungs, liver, aorta, spleen, kidneys, and vena cava. Ribs were struck by most bullets that entered the thorax. PMID- 26264377 TI - Neuropathology in a case of episodic ataxia type 4. PMID- 26264378 TI - Phase 2 study of sunitinib in patients with metastatic mucosal or acral melanoma. AB - BACKGROUND: Patients with mucosal and acral melanomas have limited treatment options and a poor prognosis. Mutations of the KIT oncogene in these melanoma subtypes provide a potential therapeutic target. METHODS: A multicenter phase 2 trial of sunitinib was conducted in patients with unresectable stage III or IV melanoma of a mucosal or acral primary origin. Patients were treated in 2 cohorts: cohort A received sunitinib at a dose of 50 mg daily for 4 weeks of a 6 week cycle, and cohort B received sunitinib at a dose of 37.5 mg daily on a continuous basis. Dose reductions were permitted for treatment-related toxicities, and tumor assessments were performed every 2 months. RESULTS: Fifty two patients were enrolled: 21 in cohort A and 31 in cohort B. Four patients had confirmed partial responses, which lasted 5 to 10 months (1 with a KIT mutation). In both cohorts, the proportion of patients alive and progression-free at 2 months was 52% (95% confidence interval, 38%-66%); this was significantly larger than the hypothesized null of 5%. There was no significant difference in response or overall survival between the 25% of patients with a KIT mutation and those without one (response rate, 7.7% vs 9.7%; overall survival, 6.4 vs 8.6 months). The overall disease control rate was 44%, and a high rate of toxicity was associated with the treatment. CONCLUSIONS: Sunitinib showed activity in the treatment of mucosal and acral melanoma that was not dependent on the presence of a KIT mutation. However, the medication was poorly tolerated, and there were no prolonged responses. Cancer 2015;121:4007-4015. (c) 2015 American Cancer Society. PMID- 26264379 TI - Breast cancer quality of care in Taiwan in relation to hospital volume: a population-based cohort study. AB - AIM: To evaluate, compare and improve quality of care for patients with breast cancer at the institution and population level requires a standard set of core measures. We performed a population-based cohort study to examine the association between hospital volume and breast cancer core measures compliance in Taiwan. METHODS: Data were obtained from the Health Promotion Administration, Ministry of Health and Welfare, Taiwan. All women with a diagnosis of breast cancer between 2007 and 2011 were selected. Hospitals were divided into quartiles of hospital volume based on the total number of breast cancer surgery performed from 2007 to 2011. The core measure set that evaluates the quality of care for breast cancer included one preoperation and nine treatment-related indicators. RESULTS: Our final study population included 38 943 patients from 74 hospitals. An increase in hospital volume was associated with better core measures compliance as indicated by higher adherence rates. As compared with the lower quartiles (quartiles 1/2/3) of hospital volume, quartile 4 (high volume) showed significantly higher adherence rate in two indicators measured ("percentage of breast cancer patients whose diagnoses were histologically and cytologically confirmed before surgery" and "percentage of stage 1 and 2 patients with sentinel node sampling performed," P = 0.011 and 0.016, respectively). An increasing trend in compliance for "percentage of stage 1 patients who underwent breast conserving surgery" was observed in high-volume but not low-volume hospitals (P < 0.001). CONCLUSION: This institution and population-based study showed a certain degree of variation to core measures compliance among hospitals. In some aspects of pre- and postoperative care, high-volume hospitals demonstrated higher and more improved quality as supported by increased adherence rates. Further research is needed to determine whether better core measures compliance would result in better outcomes. PMID- 26264380 TI - Is PLC repair of a peel-off femoral lesion an effective option in a multiligament setting? AB - PURPOSE: Treatment of posterolateral corner (PLC) injury in the multiligament injured knee is still controversial. The aim of this study was to investigate the clinical outcome of acute or sub-acute surgical repair of Type 1 and 2 PLC peel off lesions in a multiligament setting. METHODS: Mini-open direct repair of the PLC was performed in 13 patients. Combined PCL, ACL and MCL injuries were simultaneously managed. Telos valgus and varus stress radiographs at 30 degrees of flexion with 150 N load were used to investigate medial and lateral joint opening. Posterior stress radiograph with 150 N load was used to investigate the function of the PCL. External rotational laxity was assessed with a dial test at 30 degrees of knee flexion, and photographs were taken to measure angles. Anterior displacement was examined using the manual maximum test performed with a KT-1000 arthrometer. RESULTS: A statistically significant reduction between pre- and postoperative laxity values was achieved for every test. Particularly, lateral joint opening side-to-side difference reduced from 10.3 +/- 4.0 to 1.0 +/ 3.2 mm and external rotation reduced from 15 +/- 8 degrees to 0 degrees +/- 6 degrees more than that of the contralateral uninjured knee. The medial joint opening side-to-side difference reduced from 11.5 +/- 5.6 to 2.6 +/- 2.7 mm in the 7 patients surgically managed for MCL lesion. The anterior tibial displacement side-to-side difference reduced from 14.0 +/- 5.0 to 3.0 +/- 5.0 mm in the 9 patients surgically managed for ACL lesion. The posterior tibial translation side-to-side difference reduced from 11.1 +/- 5.1 to 4.4 +/- 3.9 mm in the 11 patients treated for PCL lesion. CONCLUSION: The main finding of the current study is that acute repair of Type 1 and 2 PLC peel-off injury proved to be an effective procedure to restore PLC function in a multiligament-injured knee. These data enabled the current literature with an effective treatment option to face such a complex and various scenarios such as multiligament-injured knee. LEVEL OF EVIDENCE: IV. PMID- 26264381 TI - Endoscopic treatment of the posterior ankle impingement syndrome on amateur and professional athletes. AB - PURPOSE: To determine whether professional and amateur athletes showed differences in ankle function when treated with endoscopic technique for posterior ankle impingement syndrome, to verify the impact of the presence of associated lesions in clinical evolution and to assess time to return to sport (we hypothesize that time will be the only difference between groups). METHODS: Thirty-two athletes with a diagnosis of posterior impingement syndrome underwent surgery endoscopically. The American Orthopaedics Foot and Ankle Society (AOFAS) scale was used to compare functional results between amateur (15) and professional athletes (17). The satisfaction, time to return to sport, operative time, intraoperative findings and complications were evaluated, and the presence of associated injuries interfering in these results was verified. RESULTS: The preoperative AOFAS score range for the professional group was 62.9 +/- 14 preoperatively and 92.3 +/- 7.7 postoperatively, and for the amateur group was 67.9 +/- 19.7 and 94 +/- 9.3. The satisfaction was excellent or good in 94 % of all cases and fair in 6%. The average time of surgery was 48.3 + 25 min. Bone involvement was present in 100% of cases and complications in three cases. Time to return to sports was similar (n.s.) in both groups, and the mean time was 15.6 +/- 13.7 and 16.3 +/- 9 weeks, respectively. CONCLUSION: No significant difference regarding functional results and time to return to sports between professionals and amateur athletes operated was found. Athletes showed mainly good and excellent results and low complication rate. The presence of associated injuries did not significantly influence the results. With these results, the high-level athlete can better programme their surgeries so they can fully recover and perform better in the most important competitions. LEVEL OF EVIDENCE: Level III. PMID- 26264383 TI - The role of the meniscotibial ligament in posteromedial rotational knee stability. AB - PURPOSE: Tears of the posterior horn of the medial meniscus (PHMM) are very common in the ACL-deficient knee. Specific lesions of the PHMM have been described in the setting of ACL rupture: ramp lesions and injuries to the meniscotibial ligament. There are little data available regarding the role these lesions play in knee instability. The aim of this study is to analyse the biomechanical consequences of ramp and meniscotibial ligament lesions on knee stability. Our hypothesis was that these lesions would cause increased instability in the setting of ACL rupture. METHODS: A cadaveric study was undertaken: ten knees were included for analysis. The biomechanical repercussions of different meniscoligamentous injuries were studied in four stages: stage 1 involved testing the intact knee, stage 2 after transection of the ACL, stage 3 following creation of a ramp lesion, and stage 4 after detachment of the meniscotibial ligament. Four parameters were measured during the experiment: anterior tibial translation under a force of 134 N, internal and external tibial rotation under a torque of 5 Nm, and valgus angulation under a torque of 10 Nm. Measurements were taken in four knee flexion positions: 0 degrees or full extension, 30 degrees , 70 degrees , and 90 degrees of flexion. RESULTS: There was a statistically significant increase in anterior tibial translation for stage 2 (6.8 +/- 1.3 mm, p <= 0.001), stage 3 (9.4 +/- 1.3 mm, p <= 0.001), and stage 4 (9.3 +/- 1.3 mm, p <= 0.001) compared to stage 1. There was no significant difference between stage 2 and stage 3 (2.6 mm, n.s.) or stage 4 (2.5 mm, n.s.). We did, however, demonstrate an increase in anterior tibial translation of 2.6 mm after the creation on a lesion of the PHMM compared to isolated division of the ACL, for all flexion angles combined. There was an increase in internal tibial rotation between stage 1 and stage 4 (3.2 degrees +/- 0.7 degrees , p <= 0.001) and between stage 2 and stage 4 (2.0 degrees +/- 0.7 degrees , p = 0.023). A significant difference was demonstrated for external rotation under 5 Nm torque between stages 4 and 1 (2.2 degrees +/- 0.5 degrees , p <= 0.001) and between stages 4 and 2 (1.7 degrees +/- 0.5 degrees , p = 0.007) for all knee flexion angles combined. No created lesion had a significant effect on medial laxity under a 10-Nm valgus torque at any degree of knee flexion. CONCLUSION: Lesions of the posterior horn of the medial meniscus are frequent in cases of anterior cruciate ligament rupture. These lesions appear to play a significant role in knee stability. Ramp lesions increase the forces in the ACL, and the PHMM is a secondary restraint to anterior tibial translation. Lesions of the meniscotibial ligament may increase rotatory instability of the knee. PMID- 26264382 TI - Single-dose intra-articular bupivacaine plus morphine versus bupivacaine alone after arthroscopic knee surgery: a meta-analysis of randomized controlled trials. AB - PURPOSE: The purpose of this meta-analysis was to compare the efficacy and safety of single-dose intra-articular bupivacaine plus morphine versus bupivacaine alone for pain management following arthroscopic knee surgery. METHOD: A comprehensive literature search was conducted to identify randomized controlled trials that used single-dose intra-articular bupivacaine plus morphine and bupivacaine alone for post-operative pain, using MEDLINE (1966-2014), Cochrane Library and EMBASE databases. The weighted mean difference (WMD), relative risk (RR) and their corresponding 95 % confidence intervals (CIs) were calculated using RevMan statistical software. RESULT: A total of twenty-nine trials (n = 1167) were included. The post-operative visual analog scale (VAS) pain score of the bupivacaine plus morphine group compared with the bupivacaine alone group was significantly lower (WMD -1.15, 95 % CI -1.67 to -0.63, p < 0.0001). As far as safety, there was no significant difference in side effects between the two groups (RR 1.10, 95 % CI 0.59-2.04, n.s.). Sensitivity analyses suggested that the results of these two primary outcomes were stable and reliable. However, the current evidence did not suggest a superior effect with respect to the time to first analgesic request (WMD 51.33, 95 % CI -110.99 to 213.65, n.s.) and the number of patients requiring supplementary analgesia (RR 1.13, 95 % CI 0.92-1.39, n.s.). CONCLUSIONS: On the basis of the currently available literature, this study is the first to suggest that single-dose intra-articular bupivacaine plus morphine was shown to be significantly better than bupivacaine alone at relieving post-operative pain after arthroscopic knee surgery without increasing the short term side effects. Routine use of single-dose intra-articular bupivacaine plus morphine is an effective way for pain management after arthroscopic knee surgery. LEVEL OF EVIDENCE: II. PMID- 26264384 TI - TWEAK/Fn14 activation induces keratinocyte proliferation under psoriatic inflammation. AB - Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) has been reported to induce keratinocyte apoptosis in vitro by engaging its sole receptor of fibroblast growth factor-inducible 14 (Fn14). In this study, we explored the role of TWEAK/Fn14 pathway in the growth of psoriatic keratinocytes that is, however, characterized by suppressed apoptotic cell death. Skin tissues from the patients with psoriasis or healthy donors were determined for TWEAK and Fn14 expression, and primary keratinocytes were evaluated under the stimulation of psoriatic proinflammatory cytokines or plus TWEAK. The results showed that both TWEAK and Fn14 were highly expressed in psoriatic skins. Moreover, the stimulation of psoriatic cytokines enhanced Fn14 expression by keratinocytes in vitro, which expressed TNF receptor 2 predominantly and proliferated increasingly with the addition of TWEAK. Furthermore, TWEAK stimulation enhanced the synthesis of survivin, inhibitor of apoptosis protein 2 and cellular FLICE-inhibitory protein in lesional keratinocytes. Therefore, TWEAK/Fn14 interaction prefers to enhance proliferation but not apoptosis of keratinocytes under psoriatic inflammation. The activation of nuclear factor-kappaB signalling-dependent anti apoptotic proteins and biased expression of TNF receptors may be responsible for such a novel principle in keratinocytes under psoriatic inflammation. PMID- 26264385 TI - Calcium phosphate crystallization on titania in a flowing Kokubo solution. AB - Dry titania layers on air-oxidized titanium substrates have been found to be active enough to cause apatite to be deposited in Kokubo's simulated body fluid (SBF) in narrow confined spaces, such as those in narrow grooves and thin gaps. Such in vitro apatite deposition is the basis of the GRAPE((r)) technique. The aim of the present study is to determine why GRAPE conditions favor apatite deposition when laminar SBF flow (at 0.01-0.3 ml/min) passes through a shallow channel (0.5 mm) between a pair of titanium substrates each with a dry layer of titania. Assessing the factors that control the heterogeneous nucleation process led to the proposal of the working hypothesis that there are nucleation pre embryos, ion assemblies that can be stabilized to form embryos, on the titania layer but that they are removed by the SBF flow. Specimens were subjected to different combinations of processes. One combination was that titania layers were exposed to still or flowing SBF, and the other was that half of a specimen, the inlet or outlet side, was exposed to still or flowing SBF with the other half being covered. The surface morphologies of the specimens were then compared in detail. The conclusion was that exposure to still SBF for 2 days before exposure to flowing SBF was required for apatite to be deposited. Some complicated apatite deposition modes were observed, e.g., apatite was deposited even on areas unexposed to still SBF. All of the results were successfully interpreted using the working hypothesis. The conclusion was that the GRAPE((r)) technique depends on the confined space holding pre-embryo and embryo assemblies. PMID- 26264386 TI - Recommendations for post-surgical thyroid ablation in differentiated thyroid cancer: a 2015 position statement of the Italian Society of Endocrinology. AB - Post-surgical ablation of thyroid remnant with radioactive iodine (RAI) in differentiated thyroid cancer (DTC) is aimed to destroy any thyroid remnant in the thyroid bed (remnant ablation) and any microscopic foci of cancer cells eventually present within the thyroid remnant (adjuvant therapy). The present text is an attempt to offer practice guidelines for the indication of thyroid ablation and the preparation of DTC patients considering the latest achievement in the field and the changing epidemiology of DTC observed in the last 10 years. METHODOLOGY: The executive committee of the Italian Society of Endocrinology appointed a task force of thyroid cancer expert including Nuclear Medicine Physicians and Endocrinologists to provide a consensus on the post-surgical ablation in thyroid cancer patients. The task force had no conflict of interest and had no commercial support. A number of specific topics were selected and the members selected relevant papers by searching in the Pubmed for articles published from 2000 to January 2015. Selected studies were categorized by level of evidence, and the recommendations were graded according to the level of evidence as high (A), moderate (B), or low (C). PMID- 26264387 TI - Differential effects of calcium- and vitamin D-fortified milk with FOS-inulin compared to regular milk, on bone biomarkers in Chinese pre- and postmenopausal women. AB - PURPOSE: To compare the effects of a high-calcium vitamin D-fortified milk with added FOS-inulin versus regular milk on serum parathyroid hormone, and bone turnover markers in premenopausal (Pre-M) and postmenopausal (PM) women over 12 weeks. METHODS: Premenopausal women (n = 136, mean age 41 (+/-5) years) and postmenopausal women [n = 121, mean age 59 (+/-4) years] were recruited, and each age group randomised into two groups to take two glasses per day of control = regular milk (500 mg calcium per day) or intervention (Int) = fortified milk (1000 mg calcium for pre-M women and 1200 mg calcium for PM women, 96 mg magnesium, 2.4 mg zinc, 15 ug vitamin D, 4 g FOS-inulin per day). At baseline, week 4 and week 12 serum minerals and bone biochemical markers were measured and bone density was measured at baseline. RESULTS: Mean 25-hydroxyvitamin D [25(OH) vitamin D3] levels among groups were between 49 and 65 nmol/L at baseline, and over the 12 weeks of supplementation, the fortified milk improved vitamin D status in both Int groups. CTx-1 and PINP reduced significantly in both Pre-M and PM groups over the 12 weeks, with the changes in CTx-1 being significantly different (P < 0.035) between PM control and PM Int groups at week 12. Parathyroid hormone levels were significantly reduced in all groups over time, except for control PM group where levels increased at 12 weeks. CONCLUSION: The overall pattern of responses indicates that while both regular milk and fortified milk reduce bone resorption in young and older women, fortified milk is measurably more effective. PMID- 26264388 TI - Time-dependent cellular response in the liver and heart in a dietary-induced obese mouse model: the potential role of ER stress and autophagy. AB - PURPOSE: Both endoplasmic reticulum stress (ER stress) and autophagy are essential for the response of the protein quality control system to cellular stresses. This study investigated the influence of the duration of a high-fat diet (HFD) in mice on tissue-specific cellular responses, specifically with regard to the role of autophagy and ER stress. METHODS: Male mice aged 6-7 weeks were fed ad libitum with a standard chow diet or with a HFD for 2, 4, 8, or 16 weeks. RESULTS: The HFD progressively increased mean body weight and induced tissue hypertrophy. The expression of PERK was suppressed in the liver after 16 weeks of the HFD and in the heart after 8 weeks of the HFD. Procaspase 12 and its activated form were induced in the liver with the HFD after 2 weeks, but not in the heart over the 16-week period. The activation of hepatic AMPK was elevated following 4 weeks of the HFD, but was inhibited after 16 weeks of the HFD. The ratio of LC3II to LC3I in the liver did not increase except in those mice fed the HFD for 16 weeks. The expression of AMPK and LC3 in the heart did not change over the entire 16 weeks of feeding the HFD. Cleaved PARP was increased in the liver and heart of mice receiving the HFD for 8 weeks. CONCLUSIONS: This study provides evidence that a HFD affects the cellular protein quality control processes responsible for metabolic disorder in a tissue- and duration-dependent manner. PMID- 26264389 TI - The MS@Work study: a 3-year prospective observational study on factors involved with work participation in patients with relapsing-remitting Multiple Sclerosis. AB - BACKGROUND: Multiple Sclerosis (MS) is the most common cause of neurological disability in young and middle-aged adults. At this stage in life most people are in the midst of their working career. The majority of MS patients are unable to retain employment within 10 years from disease onset. Leading up to unemployment, many may experience a reduction in hours or work responsibilities and increased time missed from work. The MS@Work study examines various factors that may influence work participation in relapsing-remitting MS patients, including disease-related factors, the working environment and personal factors. METHODS/DESIGN: The MS@Work study is a multicenter, 3-year prospective observational study on work participation in patients with relapsing-remitting MS. We aim to include 350 patients through 15-18 MS outpatient clinics in the Netherlands. Eligible participants are 18 years and older, and either currently employed or within three years since their last employment. At baseline and after 1, 2 and 3 years, the participants are asked to complete online questionnaires (including questions on work participation, work problems and accommodations, cognitive and physical ability, anxiety, depression, psychosocial stress, quality of life, fatigue, empathy, personality traits and coping strategies) and undergo cognitive and neurological examinations. After six months, patients are requested to only complete online questionnaires. Patient perspectives on maintaining and improving work participation and reasons to stop working are gathered through semi-structured interviews in a sub-group of patients. DISCUSSION: Prospective studies with long-term follow-up on work participation in MS are rare, or take into account a limited number of factors. The MS@Work study provides a 3-year follow-up on various factors that may influence work participation in patients with relapsing-remitting MS. We aim to identify factors that relate to job loss and to provide information about preventative measures for physicians, psychologists and other professionals working in the field of occupational health. PMID- 26264391 TI - Benefits and Barriers of Cancer Practitioners Discussing Physical Activity with their Cancer Patients. AB - Our aim was to synthesise the existing empirical literature and theoretical perspectives on the physical activity (PA) promotion practices and determinants of cancer clinicians and health professionals. We conducted a narrative review of theory and evidence to develop practice recommendations for improving the promotion of PA to cancer patients. Surveyed health professionals were aware of many benefits of PA for their cancer patients, although only ~40 % promoted PA to selected cancer patients. Walking was the most commonly promoted form of PA, with this promoted to assist patients control their weight and cardiovascular health risk. Barriers to promotion of PA included lack of time and knowledge of PA and behaviour change skills. Health professionals appear interested in promoting PA to their cancer patients, yet encounter several barriers. Further research is warranted to assist health professionals improve their PA promotion. An adapted reflective-impulsive model of social behaviour shows promise for assisting health professionals overcome barriers and provides an evidence-based theoretical framework for improving communication with patients. Universities, hospitals and/or health-care accreditation organisations also have important roles to play in assisting health professionals improve their promotion of PA to patients. PMID- 26264390 TI - Why Wait Until Our Community Gets Cancer?: Exploring CRC Screening Barriers and Facilitators in the Spanish-Speaking Community in North Carolina. AB - Colorectal cancer (CRC) is a leading cause of death among Hispanics in the United States. Despite the benefits of CRC screening, many Hispanics are not being screened. Using a combined methodology of focus groups and discrete choice experiment (DCE) surveys, the objectives for this research were as follows: (1) to improve understanding of preferences regarding potential CRC screening program characteristics, and (2) to improve understanding of the barriers and facilitators around CRC screening with the Hispanic, immigrant community in North Carolina. Four gender-stratified focus groups were conducted and DCE surveys were administered to 38 Spanish-speaking individuals across four counties in North Carolina. In-depth content analysis was used to examine the focus group data; descriptive analyses and mean attribute importance scores for cost of screening and follow-up care, travel time, and test options were calculated from DCE data. Data analyses showed that this population has a strong interest in CRC screening but experience barriers such as lack of access to resources, cost uncertainty, and stigma. Some of these barriers are unique to their cultural experiences in the United States, such as an expressed lack of tailored CRC information. Based on the DCE, cost variables were more important than testing options or travel time. This study suggests that Hispanics may have a general awareness of and interest in CRC screening, but multiple barriers prevent them from getting screened. Special attention should be given to designing culturally and linguistically appropriate programs to improve access to healthcare resources, insurance, and associated costs among Hispanics. PMID- 26264392 TI - Hospital outpatient clinics as a potential hazard for healthcare associated infections. AB - Healthcare acquired infections are no longer confined to the hospital environment. Recently, many reported outbreaks have been linked to outpatient settings and attributed to non-adherence to recommended infection-prevention procedures. This study was divided into two parts: The first is a descriptive cross-sectional part, to assess the healthcare personnel's knowledge and compliance with Standard Precautions (SP). The second is an intervention part to assess the role of health education on reducing the level of environmental and reusable medical equipment bacterial contamination. Assessment of the doctors' and nurses' knowledge and compliance with SP was performed using a self administered questionnaire. Assessment of environmental cleaning (EC) and reusable medical equipment disinfection has been performed using aseptic swabbing method. The extent of any growth was recorded according to the suggested standards: (A) Presence of indicator organisms, with the proposed standard being <1cfu/cm(2). These include Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus, MRSA), Enterococci, including vancomycin-resistant Enterococci (VRE) and various multidrug-resistant Gram-negative bacilli. (B) Aerobic colony count, the suggested standard is <5cfu/cm(2). The effect of health education intervention on cleaning and disinfection had been analyzed by comparing the difference in cleaning level before and after interventional education. Good knowledge and compliance scores were found in more than 50% of participants. Primary screening found poor EC and equipment disinfection as 67% and 83.3% of stethoscopes and ultrasound transducers, respectively, were contaminated with indicator organisms. For all indicator organisms, a significant reduction was detected after intervention (p=0.00). Prevalence of MRSA was 38.9% and 16.7%, of the total S. aureus isolates, before and after intervention, respectively. Although 27.8% of the total Enterococcus isolates were VRE before intervention, no VRE isolates were detected after intervention. These differences were significant. Development and monitoring of the implementation of infection prevention policies and training of HCP is recommended. PMID- 26264393 TI - Key messages from a guideline. Management of petechial rash. PMID- 26264394 TI - Y-doped Li8ZrO6: A Li-Ion Battery Cathode Material with High Capacity. AB - We study--experimentally and theoretically--the energetics, structural changes, and charge flows during the charging and discharging processes for a new high capacity cathode material, Li8ZrO6 (LZO), which we study both pure and yttrium doped. We quantum mechanically calculated the stable delithiated configurations, the delithiation energy, the charge flow during delithiation, and the stability of the delithiated materials. We find that Li atoms are easier to extract from tetrahedral sites than octahedral ones. We calculate a large average voltage of 4.04 eV vs Li/Li(+) for delithiation of the first Li atom in a primitive cell, which is confirmed by galvanostatic charge/discharge cycling data. Energy calculations indicate that topotactic delithiation is kinetically favored over decomposition into Li, ZrO2, and O2 during the charging process, although the thermodynamic energy of the topotactic reaction is less favorable. When one or two lithium atoms are extracted from a primitive cell of LZO, its volume and structure change little, whereas extraction of the third lithium greatly distorts the layered structure. The Li6ZrO6 and Li5ZrO6 delithiation products can be thermodynamically metastable to release of O2. Experimentally, materials with sufficiently small particle size for efficient delithiation and relithiation were achieved within an yttrium-doped LZO/carbon composite cathode that exhibited an initial discharge capacity of at least 200 mAh/g over the first 10 cycles, with 142 mAh/g maintained after 60 cycles. Computations predict that during the charging process, the oxygen ion near the Li vacancy is oxidized for both pure LZO and yttrium-doped LZO, which leads to a small-polaron hole. PMID- 26264395 TI - Suppression effects of O-demethyldemethoxycurcumin on thapsigargin triggered on endoplasmic reticulum stress in SK-N-SH cells. AB - Endoplasmic reticulum (ER) stress is involved in neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Therefore, interventions that attenuate ER stress may contribute to induction in apoptotic cell death. This study aimed to evaluate the potential involvement of O demethyldemethoxycurcumin, an analog of curcuminoids, on thapsigargin-induced apoptosis in cultured neuroblastoma (SK-N-SH) cells through the ER stress signaling pathway. The results showed that O-demethyldemethoxycurcumin reduced thapsigargin induced cell death in SK-N-SH cells and the release of lactate dehydrogenase (LDH) by decreasing the apoptotic cell death induced by thapsigargin. Consistent with these findings, O-demethyldemethoxycurcumin inhibited the thapsigargin-induced activation of cleavagecaspase-12. Moreover, O demethyldemethoxycurcumin attenuated the intracellular Ca(2+) level and the expression of the calpain protein. O-demethyldemethoxycurcumin also downregulated the expression of ER stress signaling proteins, including the phosphorylation of PKR-like endoplasmic reticulum kinase (p-PERK), the phosphorylation of inositol requiring enzyme 1 (p-IRE1), activating transcription factor 6 (ATF6), binding immunoglobulin protein (BiP) and C/EBP homologous protein (CHOP). Our findings suggest that O-demethyldemethoxycurcumin could protect against thapsigargin induced ER stress in SK-N-SH cells. PMID- 26264396 TI - Structural and multi-scale rheophysical investigation of diphasic magneto sensitive materials based on biopolymers. AB - We present a structural and a multi-scale rheophysical investigation of magneto sensitive materials based on biopolymers, namely aqueous solutions of sodium alginate incorporating magnetic maghemite nanoparticles, functionalized with adsorbed negative citrate ions. The large alginate ionic strength impacts the structure and the rheology of these nanocomposites in zero magnetic field. In given physico-chemical conditions, the system is fluid and homogeneous on macroscopic scales while it is diphasic on microscopic ones, containing micro droplets coming from the demixion of the system. These micro-droplets are liquid and deformable under magnetic field. Their under-field elongation and their zero field relaxation are directly observed by optical microscopy to determine their interfacial tension, their magnetic susceptibility and their internal viscosity. A structural analysis of the solutions of alginate chains and of the phase separated mixtures of alginate and nanoparticles by Small Angle Scattering completes the local description of the system. PMID- 26264397 TI - Nutritional alterations after very low-calorie diet before bariatric surgery. AB - INTRODUCTION: There has been an alarming worldwide increase of obese people in recent years. Currently, there is no consensus on whether patients that are scheduled to undergo bariatric surgery should lose weight before the intervention. The objective of this research is to analyse the influence of pre surgery loss of weight in the nutritional parameters of patients. METHODS: Fifty patients that were scheduled to undergo bariatric surgery followed a very low caloric diet during 4 weeks prior to the surgery. The nutritional parameters were analysed at 3 specific moments: before starting the diet, at the moment of surgery (when the diet was concluded) and one month after the surgery. RESULTS: Average values for hemoglobin, albumina and lymphocytes were kept within the range of normal values at all moments, even though the decrease of those parameters was statistically significant throughout the study (P<.05). By following the very low caloric diet, less than 9.5% of the sample suffered anaemia. CONCLUSIONS: Loss of weight prior to surgery does not have a significant influence in the nutritional parameters of the patient. These results would support the indication of losing weight for patients that are considered candidates for bariatric surgery. PMID- 26264398 TI - Pretreating wheat straw by the concentrated phosphoric acid plus hydrogen peroxide (PHP): Investigations on pretreatment conditions and structure changes. AB - Wheat straw was pretreated by PHP (the concentrated H3PO4 plus H2O2) to clarify effects of temperature, time and H3PO4 proportion on hemicellulose removal, delignification, cellulose recovery and enzymatic digestibility. Overall, hemicellulose removal was intensified by PHP comparing to the concentrated H3PO4. Moreover, efficient delignification specially happened in PHP pretreatment. Hemicellulose removal and delignification by PHP positively responded to temperature and time. Increasing H3PO4 proportion in PHP can promote hemicellulose removal, however, decrease the delignification. Maximum hemicellulose removal and delignification were achieved at 100% and 83.7% by PHP. Enzymatic digestibility of PHP-pretreated wheat straw was greatly improved by increasing temperature, time and H3PO4 proportion, and complete hydrolysis can be achieved consequently. As temperature of 30-40 degrees C, time of 2.0 h and H3PO4 proportion of 60% were employed, more than 92% cellulose was retained in the pretreated wheat straw, and 29.1-32.6g glucose can be harvested from 100g wheat straw. PMID- 26264399 TI - Effects of exenatide on measures of diabetic neuropathy in subjects with type 2 diabetes: results from an 18-month proof-of-concept open-label randomized study. AB - OBJECTIVE: Experimental studies have reported potential benefit of glucagon-like peptide-1(GLP-1) receptor agonists in preventing diabetic peripheral neuropathy (DPN). We therefore performed a proof-of-concept pilot study to evaluate the effect of exenatide, a GLP-1 agonist, on measures of DPN and cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: Forty-six T2D subjects (age 54+/-10years, diabetes duration 8+/-5years, HbA1c 8.2+/-1.3%) with mild to moderate DPN at baseline were randomized to receive either twice daily exenatide (n=22) or daily insulin glargine (n=24). The subjects, with similar HbA1c levels, were followed for 18months. The primary end point was the prevalence of confirmed clinical neuropathy (CCN). Changes in measures of CAN, other measures of small fiber neuropathy such as intra-epidermal nerve fiber density (IENFD), and quality of life were also analyzed. RESULTS: Glucose control was similar in both groups during the study. There were no statistically significant treatment group differences in the prevalence of CCN, IENFD, measures of CAN, nerve conductions studies, or quality of life indices. CONCLUSIONS: In this pilot study of patients with T2D and mild to moderate DPN, 18months of exenatide treatment had no significant effect on measures of neuropathy compared with glargine treatment. PMID- 26264400 TI - Comparison of glycemic control and variability in patients with type 2 and posttransplantation diabetes mellitus. AB - AIM: Posttransplantation diabetes mellitus (PTDM) is a common complication after renal transplantation leading to increased cardiovascular morbidity and mortality. In subjects with type 2 diabetes (T2DM) increased glycemic variability and poor glycemic control have been associated with cardiovascular complications. We therefore aimed at determining glycemic variability and glycemic control in subjects with PTDM in comparison to T2DM subjects. METHODS: In this observational study we analyzed 10 transplanted subjects without diabetes (Control), 10 transplanted subjects with PTDM, and 8 non-transplanted T2DM subjects using Continuous Glucose Monitoring (CGM). Several indices of glycemic control quality and variability were computed. RESULTS: Many indices of both glycemic control quality and variability were different between control and PTDM subjects, with worse values in PTDM. The indices of glycemic control, such as glucose mean, GRADE and M-value, were similar in PTDM and T2DM, but some indices of glycemic variability, that is CONGA, lability index and shape index, showed a markedly higher (i.e., worse) value in T2DM than in PTDM (P value range: 0.001-0.035). CONCLUSIONS: Although PTDM and T2DM subjects showed similar glycemic control quality, glycemic variability was significantly higher in T2DM. These data underscore potential important pathophysiological differences between T2DM and PTDM indicating that increased glycemic variability may not be a key factor for the excess cardiovascular mortality in patients with PTDM. PMID- 26264401 TI - Accumulation status, sources and phytoavailability of metals in greenhouse vegetable production systems in Beijing, China. AB - The accumulation status, sources and phytoavailability of selected metals in greenhouse vegetable production systems in peri-urban areas of Beijing were investigated. The mean concentrations of As, Cd, Cr, Hg and Pb in greenhouse soils were 8.44, 0.25, 69.0, 0.09 and 22.0 mg kg(-1), dw, respectively. According to principal component analysis, As, Cd, Cr and Hg are mainly from anthropogenic source, but Pb is likely from natural source. Metal concentrations in all vegetable samples were decreased in the order of Cr>As>Pb>Cd>Hg. Compared with root and fruit vegetables, leaf vegetables had relatively high concentrations and transfer factors of heavy metals, except for Cd. By including soil pH, OM and greenhouse soil metals, 10 empirical models were derived using stepwise multiple linear regression analysis to predict heavy metal concentrations in the edible parts of different vegetables. Among the different vegetable groups, the highest intakes of metals occurred through consumption of leaf vegetables for the two age groups, except for Cd. The HI value of the studied metals were all below 1, indicating that consumption of vegetables grown in greenhouse soils was of low risk to consumers in our study area. PMID- 26264402 TI - Nucleotide sequence and genome organization of a new proposed crinivirus, tetterwort vein chlorosis virus. AB - The genome of tetterwort vein chlorosis virus (TVCV) from South Korea has been completely sequenced. Its genomic organization resembles those of other criniviruses, with several new features, indicating that TVCV is a member of a new species in the genus Crinivirus, family Closteroviridae. RNA1 contains 8467 nucleotides, with at least four opening reading frames (ORFs). ORF1a encodes a protein with predicted papain-like protease, methyltransferase, and helicase activities. ORF1b encodes a putative RNA-dependent RNA polymerase that is apparently expressed through a +1 ribosomal frameshift. RNA2 contains 8113 nucleotides encoding at least nine proteins, similar to most crinivirus RNA2s. The 3' untranslated regions of the bipartite RNA genome share 82.1% nucleotide sequence identity. PMID- 26264403 TI - Nucleotide sequence and genome organization of atractylodes mottle virus, a new member of the genus Carlavirus. AB - The complete genome sequence of a member of a distinct species of the genus Carlavirus in the family Betaflexiviridae, tentatively named atractylodes mottle virus (AtrMoV), has been determined. Analysis of its genomic organization indicates that it has a single-stranded, positive-sense genomic RNA of 8866 nucleotides, excluding the poly(A) tail, and consists of six open reading frames typical of members of the genus Carlavirus. The individual open reading frames of AtrMoV show moderately low sequence similarity to those of other carlaviruses at the nucleotide and amino acid sequence levels. Pairwise comparison and phylogenetic analysis suggest that AtrMoV is most closely related to chrysanthemum virus B. PMID- 26264404 TI - Detection and genetic variation analysis of grapevine fanleaf virus (GFLV) isolates in China. AB - To investigate the prevalence and genetic variation of grapevine fanleaf virus (GFLV) in China, 142 grapevine samples from 13 provinces and regions were tested using DAS-ELISA, RT-PCR, and nested RT-PCR. Of the samples, 38% tested positive for GFLV by DAS-ELISA, and 26.8% tested positive by RT-PCR and nested RT-PCR. Movement protein (MP) and coat protein (CP) gene PCR products were cloned and sequenced. The MP or CP nucleotide and protein sequences shared identities that ranged from 94.9% to 100%. Phylogenetic analysis revealed that Chinese GFLV isolates obtained in this study were distinct from the isolates reported in GenBank. PMID- 26264405 TI - Two-Photon Sensing and Imaging of Endogenous Biological Cyanide in Plant Tissues Using Graphene Quantum Dot/Gold Nanoparticle Conjugate. AB - One main source of cyanide (CN(-)) exposure for mammals is through the plant consumption, and thus, sensitive and selective CN(-) detection in plants tissue is a significant and urgent work. Although various fluorescence probes have been reported for CN(-) in water and mammalian cells, the detection of endogenous biological CN(-) in plant tissue remains to be explored due to the high background signal and large thickness of plant tissue that hamper the effective application of traditional one-photo excitation. To address these issues, we developed a new two-photo excitation (TPE) nanosensor using graphene quantum dots (GQDs)/gold nanoparticle (AuNPs) conjugate for sensing and imaging endogenous biological CN(-). With the benefit of the high quenching efficiency of AuNPs and excellent two-photon properties of GQDs, our sensing system can achieve a low detection limit of 0.52 MUM and deeper penetration depth (about 400 MUm) without interference from background signals of a complex biological environment, thus realizing sensing and imaging of CN(-) in different types of plant tissues and even monitoring CN(-) removal in food processing. To the best of our knowledge, this is the first time for fluorescent sensing and imaging of CN(-) in plant tissues. Moreover, our design also provides a new model scheme for the development of two-photon fluorescent nanomaterial, which is expected to hold great potential for food processing and safety testing. PMID- 26264406 TI - Examining the role of collaboration in studies of health information technologies in biomedical informatics: A systematic review of 25 years of research. AB - PURPOSE: Our objective was to identify and examine studies of collaboration in relation to the use of health information technologies (HIT) in the biomedical informatics field. METHODS: We conducted a systematic literature review of articles through PubMed searches as well as reviewing a variety of individual journals and proceedings. Our search period was from 1990-2015. We identified 98 articles that met our inclusion criteria. We excluded articles that were not published in English, did not deal with technology, and did not focus primarily on individuals collaborating. RESULTS: We categorized the studies by technology type, user groups, study location, methodology, processes related to collaboration, and desired outcomes. We identified three major processes: workflow, communication, and information exchange and two outcomes: maintaining awareness and establishing common ground. Researchers most frequently studied collaboration within hospitals using qualitative methods. DISCUSSION: Based on our findings, we present the "collaboration space model", which is a model to help researchers study collaboration and technology in healthcare. We also discuss issues related to collaboration and future research directions. CONCLUSION: While collaboration is being increasingly recognized in the biomedical informatics community as essential to healthcare delivery, collaboration is often implicitly discussed or intertwined with other similar concepts. In order to evaluate how HIT affects collaboration and how we can build HIT to effectively support collaboration, we need more studies that explicitly focus on collaborative issues. PMID- 26264408 TI - Optogenetic dissection of neural circuitry: from synaptic causalities to blue prints for novel treatments of behavioral diseases. AB - Optogenetics has enabled the characterization of the neural circuits involved in brain diseases, such as addiction, depression or obsessive compulsive disorders. Recently, the technique has also been used to propose blueprints for novel treatments aiming at restoring circuit function through the reversal of specific forms of synaptic plasticity. Since optogenetic manipulations cannot be immediately translated to human use, we argue that an intermediate strategy could consist of emulating optogenetic protocols with deep brain stimulation (DBS). This translational path to rational, optogenetically inspired DBS protocols starts by refining existing approaches and carries the hope to expand to novel indications. PMID- 26264407 TI - Proton Magnetic Resonance Spectroscopy: Relevance of Glutamate and GABA to Neuropsychology. AB - Proton Magnetic Resonance Spectroscopy (MRS) has been widely used to study the healthy and diseased brain in vivo. The availability of whole body MR scanners with a field strength of 3 Tesla and above permit the quantification of many metabolites including the neurotransmitters glutamate (Glu) and gamma aminobutyric acid (GABA). The potential link between neurometabolites identified by MRS and cognition and behavior has been explored in numerous studies both in healthy subjects and in patient populations. Preliminary findings suggest direct or opposite associations between GABA or Glu with impulsivity, anxiety, and dexterity. This chapter is intended to provide an overview of basic principles of MRS and the literature reporting correlations between GABA or Glu and results of neuropsychological assessments. PMID- 26264410 TI - Telemedicine interventions for gestational diabetes mellitus: A systematic review and meta-analysis. AB - OBJECTIVE: To evaluate the effect of telemedicine on GDM service and maternal, and foetal outcomes. METHODS: A systematic review and meta-analysis of randomised controlled trials (RCT) of telemedicine interventions for GDM was conducted. We searched English publications from 01/01/1990 to 31/08/2013, with further new publication tracking to June 2015 on MEDLINE, EMBASE, PUBMED, CINAHL, the Cochrane Central Register of Controlled Trials and the World Health Organization International Clinical Trials Registry electronic databases. Findings are presented as standardised mean difference (SMD) and odds ratios (OR) or narrative and quantitative description of findings where meta-analysis was not possible. RESULTS: Our search yielded 721 abstracts. Four met the inclusion criteria; two publications arose from the same study, resulting in three studies for review. All studies compared telemedicine to usual care. Telemedicine was associated with significantly fewer unscheduled GDM clinic visits, SMD. Quality of life, glycaemic control (HbA1c, pre and postprandial blood glucose level (BGL)), and caesarean section rate were similar between the telemedicine and usual care groups. None of the studies evaluated costs. CONCLUSIONS: Telemedicine has the potential to streamline GDM service utilisation without compromising maternal and foetal outcomes. Its advantage may lie in the convenience of reducing face-to face and unscheduled consultations. Studies are limited and more trials that include cost evaluation are required. PMID- 26264409 TI - Variable alterations of the microbiota, without metabolic or immunological change, following faecal microbiota transplantation in patients with chronic pouchitis. AB - Faecal microbiota transplantation (FMT) is effective in the treatment of Clostridium difficile infection, where efficacy correlates with changes in microbiota diversity and composition. The effects of FMT on recipient microbiota in inflammatory bowel diseases (IBD) remain unclear. We assessed the effects of FMT on microbiota composition and function, mucosal immune response, and clinical outcome in patients with chronic pouchitis. Eight patients with chronic pouchitis (current PDAI >=7) were treated with FMT via nasogastric administration. Clinical activity was assessed before and four weeks following FMT. Faecal coliform antibiotic sensitivities were analysed, and changes in pouch faecal and mucosal microbiota assessed by 16S rRNA gene pyrosequencing and (1)H NMR spectroscopy. Lamina propria dendritic cell phenotype and cytokine profiles were assessed by flow cytometric analysis and multiplex assay. Following FMT, there were variable shifts in faecal and mucosal microbiota composition and, in some patients, changes in proportional abundance of species suggestive of a "healthier" pouch microbiota. However, there were no significant FMT-induced metabolic or immunological changes, or beneficial clinical response. Given the lack of clinical response following FMT via a single nasogastric administration our results suggest that FMT/bacteriotherapy for pouchitis patients requires further optimisation. PMID- 26264411 TI - Subjective sleep impairment in adults with type 1 or type 2 diabetes: Results from Diabetes MILES--The Netherlands. AB - AIMS: Despite growing recognition of the impact of sleep on diabetes, a clear profile of people with diabetes regarding subjective sleep impairment has yet to be established. This study examines: (1) subjective sleep characteristics in adults with type 1 and type 2 diabetes; (2) the relationship of poor subjective sleep quality with glycaemic control, self-care and daytime functioning; (3) possible risk markers for poor sleep quality. METHODS: In a cross-sectional study, Dutch adults with type 1 (n=267) or type 2 diabetes (n=361) completed an online survey, including the Pittsburgh Sleep Quality Index (PSQI), socio demographic, clinical, self-care and psychological measures. RESULTS: Poor sleep quality (PSQI-score >5) was reported by 31% of adults with type 1 and 42% of adults with type 2 diabetes. Participants with good and poor sleep quality did not differ in self-reported HbA1c or the frequency of meeting lifestyle recommendations. Poor sleep quality was related to a higher self-care burden and higher levels of daytime sleepiness, fatigue, depressive and anxiety symptoms, and diabetes-specific distress. In multivariable logistic regression analyses examining risk markers, poor sleep quality was associated with depressive symptoms in adults with type 1 (OR=1.39, 95% CI 1.25-1.54) and type 2 diabetes (OR=1.31, 1.16-1.47), and with being female in those with type 2 diabetes (OR=2.72, 1.42-5.20). CONCLUSIONS: Poor subjective sleep quality is prevalent both in adults with type 1 and type 2 diabetes, and is related to poor daytime functioning and higher self-care burden. The temporal relation with depression and merits of therapy should be explored. PMID- 26264412 TI - Impact of mass media on the utilization of antenatal care services among women of rural community in Nepal. AB - BACKGROUND: Antenatal care has several benefits for expecting mothers and birth outcomes; yet many mothers do not utilise this service in Nepal. Mass media may play an important role in increasing the use of antenatal care and other maternal health services. However, the effect of mass media on increasing health service utilisation has remained an under studied area in Nepal. The aim of this study was to investigate the impact of mass media on the utilisation of antenatal care services in rural Nepal. METHODS: A community-based cross-sectional study was conducted in Sinurjoda Village Development Committee of Dhanusha District, Nepal. A total of 205 mothers of children aged under 1 year were selected using systematic random sampling. Logistic regression was employed to examine the association between selected antenatal care services and mass media exposure after adjusting for other independent variables. RESULTS: A majority of mothers were exposed to mass media. Radio was accessible to most (60.0%) of the participants followed by television (43.41%). Mothers exposed to mass media were more likely to attending antenatal visits [Odds ratio (OR) 6.28; 95% CI (1.01 38.99)], taking rest and sleep during pregnancy [OR 2.65; 95% CI (1.13-6.26)], and receiving TT immunization [OR 5.12; 95% CI (1.23-21.24)] than their non exposed counterparts. CONCLUSIONS: The study reported a positive influence of mass media on the utilisation of antenatal care services in Nepal. Therefore, further emphasis should be given to increase awareness of women of rural Nepal through mass media to improve utilisation of antenatal care services in Nepal. PMID- 26264413 TI - In vitro degradation of pure Mg in response to glucose. AB - Magnesium and its alloys are promising biodegradable biomaterials but are still challenging to be used in person with high levels of blood glucose or diabetes. To date, the influence of glucose on magnesium degradation has not yet been elucidated, this issue requires more attention. Herein, we present pure Mg exhibiting different corrosion responses to saline and Hank's solutions with different glucose contents, and the degradation mechanism of pure Mg in the saline solution with glucose in comparison with mannitol as a control. On one hand, the corrosion rate of pure Mg increases with the glucose concentration in saline solutions. Glucose rapidly transforms into gluconic acid, which attacks the oxides of the metal and decreases the pH of the solution; it also promotes the absorption of chloride ions on the Mg surface and consequently accelerates corrosion. On the other hand, better corrosion resistance is obtained with increasing glucose content in Hank's solution due to the fact that glucose coordinates Ca(2+) ions in Hank's solution and thus improves the formation of Ca P compounds on the pure Mg surface. This finding will open up new avenues for research on the biodegradation of bio-Mg materials in general, which could yield many new and interesting results. PMID- 26264415 TI - Economic Outcomes of Extracorporeal Membrane Oxygenation With and Without Ambulation as a Bridge to Lung Transplantation. AB - BACKGROUND: An increasing number of centers are using active rehabilitation and ambulation for critically ill patients on extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation. This investigation assessed the economic impact at a single center of ambulatory versus non-ambulatory ECMO strategies as a bridge to lung transplantation. METHODS: We conducted a single center retrospective cohort analysis of all subjects supported with ECMO as a bridge to lung transplantation (N = 9) from 2007 to 2012. Subjects who were rehabilitated while supported with ECMO before lung transplantation were compared with those who were not rehabilitated during ECMO. Hospital cost data for the month before transplantation through 12 months after the initial post-transplant hospital discharge were compared. RESULTS: The median cost (interquartile range [IQR]) in the 30 d before transplant for the ambulatory cohort was $88,137 (IQR $38,589-$122,111) compared with $52,124 (IQR $23,824-$69,929) for the non ambulatory cohort (P = .08). The median post-transplant ICU cost for the ambulatory cohort was $38,468 (IQR $23,611-$64,126) compared with $143,407 (IQR $112,199-$168,993) for the non-ambulatory cohort (P = .01). The median total hospital cost for subjects supported with ambulatory ECMO was $213,086 (IQR $166,767-$264,536) compared with $273,291 (IQR $237,299-$374,175) for non ambulatory ECMO subjects (P = .05). The median total cost for the ambulatory cohort was $268,194 (IQR $219,972-$517,320) compared with $300,307 (IQR $274,262 $394,913) for the non-ambulatory cohort (P = .14). CONCLUSIONS: Subjects supported with ambulatory ECMO had a 22% ($60,204) reduction in total hospital cost, 73% ($104,939) reduction in post-transplant ICU cost, and 11% ($32,133) reduction in total cost compared with non-ambulatory ECMO subjects. This analysis demonstrates the potential economic benefit of rehabilitation and ambulation during ECMO compared with a traditional strategy. PMID- 26264414 TI - Efficient enzymatic production of rebaudioside A from stevioside. AB - Stevioside and rebaudioside A are the chief diterpene glycosides present in the leaves of Stevia rebaudiana. Rebaudioside A imparts a desirable sweet taste, while stevioside produces a residual bitter aftertaste. Enzymatic synthesis of rebaudioside A from stevioside can increase the ratio of rebaudioside A to stevioside in steviol glycoside products, providing a conceivable strategy to improve the organoleptic properties of steviol glycoside products. Here, we demonstrate the efficient conversion of stevioside to rebaudioside A by coupling the activities of recombinant UDP-glucosyltransferase UGT76G1 from S. rebaudiana and sucrose synthase AtSUS1 from Arabidopsis thaliana. The conversion occurred via regeneration of UDP-glucose by AtSUS1. UDP was applicable as the initial material instead of UDP-glucose for UDP-glucose recycling. The amount of UDP could be greatly reduced in the reaction mixture. Rebaudioside A yield in 30 h with 2.4 mM stevioside, 7.2 mM sucrose, and 0.006 mM UDP was 78%. PMID- 26264416 TI - A Qualitative Exploration of Exercise Among Pulmonary Rehabilitation Participants: Insight From Multiple Sources of Social Influence. AB - BACKGROUND: Exercise training within the pulmonary rehabilitation (PR) context is considered the most effective strategy to reduce COPD symptoms. However, participation in PR and continued exercise training following program completion are low. Previous research examined factors related to attendance and adherence, but the knowledge base to date has been limited to quantitative findings that focus solely on participants diagnosed with COPD. In addition to quantitative research, exploring multiple perspectives (eg, PR participants, significant others, staff, and stakeholders) using qualitative research methods opens a window of additional understanding. The goal of this study was to obtain multiple perspectives on PR to gain insight into factors that affect exercise participation among individuals diagnosed with COPD. METHODS: A total of 26 participants were interviewed via telephone, including 8 individuals diagnosed with COPD (4 men and 4 women, mean age of 67 [range of 58-77] y), 4 family members, 11 PR staff, and 3 community stakeholders. RESULTS: Analysis revealed 3 themes: task self-efficacy for exercise, provision of support and encouragement, and perceptions of gender differences. Despite initial concerns, individuals diagnosed with COPD reported becoming more confident during PR and emphasized the importance of being supported by staff. PR staff perceived that men tended to approach exercise in a more eager and aggressive manner compared with women, who were more cautious and hesitant. CONCLUSIONS: In addition to enhancing task self efficacy, findings suggest that exercise participation and adherence within the PR environment may be improved by adopting a gender-tailored approach. PMID- 26264417 TI - Acute Mucociliary Clearance Response to Aerobic Exercise in Smokers. AB - BACKGROUND: Mucociliary clearance is the main defense mechanism of the respiratory system, and it is influenced by several stimuli, including aerobic exercise and cigarette smoking. We evaluated the acute response of mucociliary clearance to aerobic exercise in smokers and nonsmokers compared with that found after acute smoking and smoking combined with exercise. Also, we investigated whether there was a correlation between mucociliary clearance and the autonomic nervous system under these conditions. METHODS: Twenty-one smokers were evaluated for mucociliary clearance by saccharin transit time (STT), and the response of the autonomic nervous system was evaluated by heart rate variability after aerobic exercise, after exercise followed by smoking, after acute smoking, and after rest. For comparison, 17 nonsmokers were also assessed during exercise. Repeated-measures analysis of variance with the Tukey test or the Friedman test followed by the Dunn test was used to evaluate the STT, autonomic response, and other variables to exercise and/or smoking in smokers. A paired t test or Wilcoxon test was used to analyze responses to exercise in nonsmokers. Correlations were evaluated using Pearson or Spearman coefficients. RESULTS: The STT was reduced after exercise in both groups, with similar responses between them. Other stimuli also reduced the STT. The STT showed a negative correlation with sympathetic activity in smokers and a positive correlation with the parasympathetic system in nonsmokers. CONCLUSIONS: Although impaired in smokers, mucociliary clearance responded to the stimulus of exercise, as demonstrated by similar STTs compared with nonsmokers. This response was correlated with the autonomic nervous system in both groups. In smokers, mucociliary clearance also responded to the stimuli of smoking and exercise followed by smoking. PMID- 26264418 TI - Predicting the Outcomes of Subjects With Severe Community-Acquired Pneumonia Using Monocyte Human Leukocyte Antigen-DR. AB - BACKGROUND: The objective was to study the level of monocyte-human leukocyte antigen-DR (mHLA-DR), an immune function-related biomarker, at 24 h after admission, to predict the outcomes of subjects with severe pneumonia. METHODS: Subjects with severe community-acquired pneumonia (n = 102) were included in the study. Blood samples were collected from each subject 24 h after admission. Data regarding age, sex, PaO2 /FIO2, comorbidities, occurrence of altered mental status, bacteremia, septic shock, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and Sequential Organ Failure Assessment (SOFA) score within the first 24 h; the highest temperature within 24 h after admission; mechanical ventilation usage; timing of antibiotic therapy; ICU stay; and 28-d survival were collected. Expression of mHLA-DR was measured by flow cytometry. RESULTS: APACHE II score and SOFA score were significantly higher (P < .001), whereas the mHLA-DR expression was significantly lower (P < .001) in the non-survivors than in the survivors. The outcomes at day 28 after admission were significantly associated with the APACHE II score (P = .002, odds ratio [OR] = 1.27, 95% CI 1.10-1.48), the SOFA score (P = .003, OR = 1.52, 95% CI 1.15-2.00), and mHLA-DR level (P = .01, OR = 0.91, 95% CI 0.85-0.98), as shown by logistic regression. The area under the receiver operating characteristic curve was 0.877 (95% CI 0.81-0.94, P < .001), 0.862 (95% CI 0.79-0.93, P < .001), and 0.781 (95% CI 0.69-0.87, P < .001) for APACHE II score, SOFA score, and the mHLA-DR expression, respectively. The optimal threshold for mHLA-DR level was 27.2%. Kaplan-Meier survival analysis showed that subjects with mHLA-DR >= 27.2% had significantly better outcomes compared with < 27.2% level (P < .001, log rank test, hazard ratio = 0.963, 95% CI 0.94-0.99). CONCLUSIONS: mHLA-DR may be a reliable biomarker that can predict the outcomes of patients with severe community-acquired pneumonia, and 27.2% may be the cut-off value to predict the outcomes. PMID- 26264419 TI - A red emitting mitochondria-targeted AIE probe as an indicator for membrane potential and mouse sperm activity. AB - In this work, a red emission AIE active mitochondrial probe is developed. It is the first non-self-quenching mitochondria specific probe with membrane potential sensitivity. Its application in sensing the membrane potential differences in mouse sperm cells is demonstrated. PMID- 26264420 TI - Near-wall dynamics of concentrated hard-sphere suspensions: comparison of evanescent wave DLS experiments, virial approximation and simulations. AB - In this article we report on a study of the near-wall dynamics of suspended colloidal hard spheres over a broad range of volume fractions. We present a thorough comparison of experimental data with predictions based on a virial approximation and simulation results. We find that the virial approach describes the experimental data reasonably well up to a volume fraction of phi~ 0.25 which provides us with a fast and non-costly tool for the analysis and prediction of evanescent wave DLS data. Based on this we propose a new method to assess the near-wall self-diffusion at elevated density. Here, we qualitatively confirm earlier results [Michailidou, et al., Phys. Rev. Lett., 2009, 102, 068302], which indicate that many-particle hydrodynamic interactions are diminished by the presence of the wall at increasing volume fractions as compared to bulk dynamics. Beyond this finding we show that this diminishment is different for the particle motion normal and parallel to the wall. PMID- 26264421 TI - How does low temperature coupled with different pressures affect initiation mechanisms and subsequent decompositions in nitramine explosive HMX? AB - We have performed ab initio molecular dynamics simulations to study coupling effects of temperature (534-873 K) and pressure (1-20 GPa) on the initiation mechanisms and subsequent chemical decompositions of nitramine explosive 1,3,5,7 tetranitro-1,3,5,7-tetrazocane (HMX). A new initiation decomposition mechanism of HMX was found to be the unimolecular C-H bond breaking, and this mechanism was independent of the coupling effects of different temperatures and pressures. The formed hydrogen radicals could promote subsequent decompositions of HMX. Subsequent decompositions were very sensitive to the pressure at low temperatures (534 and 608 K), while the temperature became the foremost factor that affected the decomposition at a high temperature (873 K) instead of the pressure. Our study may provide a new insight into understanding the coupling effects of the temperature and pressure on the initiation decomposition mechanisms of nitramine explosives. PMID- 26264422 TI - Field propagation-induced directionality of carrier-envelope phase-controlled photoemission from nanospheres. AB - Near-fields of non-resonantly laser-excited nanostructures enable strong localization of ultrashort light fields and have opened novel routes to fundamentally modify and control electronic strong-field processes. Harnessing spatiotemporally tunable near-fields for the steering of sub-cycle electron dynamics may enable ultrafast optoelectronic devices and unprecedented control in the generation of attosecond electron and photon pulses. Here we utilize unsupported sub-wavelength dielectric nanospheres to generate near-fields with adjustable structure and study the resulting strong-field dynamics via photoelectron imaging. We demonstrate field propagation-induced tunability of the emission direction of fast recollision electrons up to a regime, where nonlinear charge interaction effects become dominant in the acceleration process. Our analysis supports that the timing of the recollision process remains controllable with attosecond resolution by the carrier-envelope phase, indicating the possibility to expand near-field-mediated control far into the realm of high field phenomena. PMID- 26264423 TI - Chemical composition and insecticidal activities of essential oils against diamondback moth, Plutella xylostella (L.) (Lepidoptera: Yponomeutidae). AB - Five Himalayan plants namely, Acorus calamus, Cedrus deodara, Aegle marmelos, Tagetes minuta and Murraya koenigii were used for the extraction of essential oils through hydrodistillation and the major volatile constituents as identified by GC and GC-MS techniques were beta-asarone (91.1%), beta-himachalene (45.8%), limonene (59.5%), Z-ocimene (37.9%) and alpha-pinene (54.2%), respectively. Essential oils were tested for their insecticidal properties against larvae of diamondback moth, Plutella xylostella (L.) (Lepidoptera: Yponomeutidae). Results showed that A. calamus was most toxic (LC50 = 0.29 mg mL(-1)) to P. xylostella followed by C. deodara (LC50 = 1.08 mg mL(-1)) and M. koenigii (LC50 = 1.93 mg mL(-1)) via residual toxicity bioassay. Per cent feeding deterrence index and growth inhibition was significantly higher in A. calamus (42.20 and 68.55, respectively) followed by C. deodara (35.41 and 52.47). In repellent activity studies, C. deodara showed high repellence (64.76%) followed by A. calamus (55.05%). PMID- 26264424 TI - Isolation and structural determination of non-racemic tertiary cathinone derivatives. AB - The racemic tertiary cathinones N,N-dimethylcathinone (1), N,N-diethylcathinone (2) and 2-(1-pyrrolidinyl)-propiophenone (3) have been prepared in reasonable yield and characterized using NMR and mass spectroscopy. HPLC indicates that these compounds are isolated as the anticipated racemic mixture. These can then be co-crystallized with (+)-O,O'-di-p-toluoyl-D-tartaric, (+)-O,O'-dibenzoyl-D tartaric and (-)-O,O'-dibenzoyl-L-tartaric acids giving the single enantiomers S and R respectively of 1, 2 and 3, in the presence of sodium hydroxide through a dynamic kinetic resolution. X-ray structural determination confirmed the enantioselectivity. The free amines could be obtained following basification and extraction. In methanol these are reasonably stable for the period of several hours, and their identity was confirmed by HPLC and CD spectroscopy. PMID- 26264425 TI - Differential effects of strength training and testosterone treatment on soluble CD36 in aging men: Possible relation to changes in body composition. AB - PURPOSE: We measured soluble CD36 (sCD36) and body composition to determine the effects of testosterone treatment (TT) and/or strength training (ST) on cardiovascular risk in men with low normal testosterone levels. METHODS: Double blinded, placebo-controlled study in 54 men aged 60-78 years with bioavailable testosterone < 7.3 nmol/L and waist > 94 cm randomized to TT (gel, 50-100 mg/day, n = 20), placebo (n = 18) or ST (n = 16) for 6 months. Moreover, the ST group was randomized to TT (ST + TT, n = 7) or placebo (ST + placebo, n = 9) after 3 months. OUTCOMES: sCD36, total and regional fat mass were established by Dual X ray absorptiometry and magnetic resonance imaging. Data are presented as median (quartiles). Kruskal-Wallis and Mann-Whitney tests were performed on delta values at 0, 3 and 6 months. RESULTS: ST + placebo decreased sCD36 levels by 21% [from 0.80 (0.68-1.22) to 0.63 (0.51-0.73) rel. units] vs. TT and vs. placebo (p < 0.05). ST + placebo did not change bioavailable testosterone and lean body mass. Fat mass measures significantly improved during ST + placebo, ST + TT, and TT vs. placebo. During ST + placebo, delta sCD36 was associated with delta total fat mass (r = 0.81) and delta central fat mass (r = 0.84). CONCLUSIONS: Compared to testosterone treatment, six months of strength training reduced sCD36 levels suggesting decreased cardiovascular risk, possibly due to a reduction in central fat mass. PMID- 26264426 TI - Validation of a competitive ELISA assay for the quantification of human serum hepcidin. AB - BACKGROUND: Hepcidin-25 is a potential marker for iron disorders with a demand for accessible assays. This study aimed to evaluate a commercial competitive enzyme-linked immunosorbent assay (cELISA) for hepcidin quantitation. METHODS: Serum samples; 95 healthy subjects (HS), six patients with iron deficiency (ID), 84 patients with liver disorders (LD) and 220 hemodialysis patients (HD), were analyzed. Controls were used for imprecision, while accuracy was evaluated by quantitating hepcidin-25 with LC-MS/MS in 149 samples. Cross-reactivity for hepcidin-20 and hepcidin-22 was tested. Hepcidin-mRNA expression in 37 liver biopsies was measured. RESULTS: S-hepcidin ranged from 8-76 and 2-31 MUg/L in healthy men and women. Levels in ID, LD and HD significantly differed from HS. Total coefficients of variation (CV) for controls were 24% and 22%. Within-sample CV was 10%. Despite a good correlation with LC-MS/MS (r = 0.89), the cELISA showed higher values and detected hepcidin-20 and hepcidin-22. Hepcidin-mRNA correlated well with S-hepcidin using cELISA and LC-MS/MS (r = 0.69 and 0.64). CONCLUSIONS: The correlation with LC-MS/MS is good and the examined kit can differentiate between patient groups although it is not specific for hepcidin-25. Considering ELISA's capacity to readily be set up, the investigated kit can be applied. Specific reference ranges are required. PMID- 26264428 TI - ImmunExplorer (IMEX): a software framework for diversity and clonality analyses of immunoglobulins and T cell receptors on the basis of IMGT/HighV-QUEST preprocessed NGS data. AB - BACKGROUND: Today's modern research of B and T cell antigen receptors (the immunoglobulins (IG) or antibodies and T cell receptors (TR)) forms the basis for detailed analyses of the human adaptive immune system. For instance, insights in the state of the adaptive immune system provide information that is essentially important in monitoring transplantation processes and the regulation of immune suppressiva. In this context, algorithms and tools are necessary for analyzing the IG and TR diversity on nucleotide as well as on amino acid sequence level, identifying highly proliferated clonotypes, determining the diversity of the cell repertoire found in a sample, comparing different states of the human immune system, and visualizing all relevant information. RESULTS: We here present IMEX, a software framework for the detailed characterization and visualization of the state of human IG and TR repertoires. IMEX offers a broad range of algorithms for statistical analysis of IG and TR data, CDR and V-(D)-J analysis, diversity analysis by calculating the distribution of IG and TR, calculating primer efficiency, and comparing multiple data sets. We use a mathematical model that is able to describe the number of unique clonotypes in a sample taking into account the true number of unique sequences and read errors; we heuristically optimize the parameters of this model. IMEX uses IMGT/HighV-QUEST analysis outputs and includes methods for splitting and merging to enable the submission to this portal and to combine the outputs results, respectively. All calculation results can be visualized and exported. CONCLUSION: IMEX is an user-friendly and flexible framework for performing clonality experiments based on CDR and V-(D)-J rearranged regions, diversity analysis, primer efficiency, and various different visualization experiments. Using IMEX, various immunological reactions and alterations can be investigated in detail. IMEX is freely available for Windows and Unix platforms at http://bioinformatics.fh-hagenberg.at/immunexplorer/. PMID- 26264429 TI - External validation of a prognostic CT-based radiomic signature in oropharyngeal squamous cell carcinoma. AB - BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) is one of the fastest growing disease sites of head and neck cancers. A recently described radiomic signature, based exclusively on pre-treatment computed tomography (CT) imaging of the primary tumor volume, was found to be prognostic in independent cohorts of lung and head and neck cancer patients treated in the Netherlands. Here, we further validate this signature in a large and independent North American cohort of OPSCC patients, also considering CT artifacts. METHODS: A total of 542 OPSCC patients were included for which we determined the prognostic index (PI) of the radiomic signature. We tested the signature model fit in a Cox regression and assessed model discrimination with Harrell's c-index. Kaplan-Meier survival curves between high and low signature predictions were compared with a log-rank test. Validation was performed in the complete cohort (PMH1) and in the subset of patients without (PMH2) and with (PMH3) visible CT artifacts within the delineated tumor region. RESULTS: We identified 267 (49%) patients without and 275 (51%) with visible CT artifacts. The calibration slope (beta) on the PI in a Cox proportional hazards model was 1.27 (H0: beta = 1, p = 0.152) in the PMH1 (n = 542), 0.855 (H0: beta = 1, p = 0.524) in the PMH2 (n = 267) and 1.99 (H0: beta = 1, p = 0.002) in the PMH3 (n = 275) cohort. Harrell's c-index was 0.628 (p = 2.72e-9), 0.634 (p = 2.7e-6) and 0.647 (p = 5.35e-6) for the PMH1, PMH2 and PMH3 cohort, respectively. Kaplan-Meier survival curves were significantly different (p < 0.05) between high and low radiomic signature model predictions for all cohorts. CONCLUSION: Overall, the signature validated well using all CT images as is, demonstrating a good model fit and preservation of discrimination. Even though CT artifacts were shown to be of influence, the signature had significant prognostic power regardless if patients with CT artifacts were included. PMID- 26264430 TI - Quercetin mitigates fenitrothion-induced testicular toxicity in rats. AB - Fenitrothion (FNT) is a widely used organophosphorus pesticide in agriculture. Quercetin (QR), a plant-derived flavonoid, has a free radical scavenging property. This study investigated the protective effect of QR on FNT-induced testicular toxicity in rats. Twenty-four male rats were divided into four groups. Group I (control) received normal saline. Group II was administered QR at the dose of 50 mg kg(-1) b.wt. Group III was orally administered FNT (20 mg kg(-1) b.wt). Group IV was gavaged FNT and QR together at the same doses. All administrations were performed daily by gavage and maintained for 70 days. Sperm parameters and histopathological changes in testes were investigated. Serum testosterone and luteinising hormone were estimated using radioimmunoassay kits. In testes, expressions of steroidogenic genes (3beta-hydroxysteroid dehydrogenase type 6, 17 beta-hydroxysteroid dehydrogenase type 3 and steroidogenic factor-1) and oxidative stress genes (catalase and superoxide dismutase) were determined using real-time PCR. FNT administration caused significant decreases in sperm count, motility and hormonal levels, a significant increase in abnormal sperm morphology and a significant down-regulation of steroidogenic and antioxidant genes in the testis. However, QR administration ameliorated FNT-induced toxic effects. Our results concluded that QR effectively mitigated testicular damage induced by FNT in rats. PMID- 26264431 TI - Computer-aided diagnosis of colorectal polyp histology by using a real-time image recognition system and narrow-band imaging magnifying colonoscopy. AB - BACKGROUND AND AIMS: It is necessary to establish cost-effective examinations and treatments for diminutive colorectal tumors that consider the treatment risk and surveillance interval after treatment. The Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) committee of the American Society for Gastrointestinal Endoscopy published a statement recommending the establishment of endoscopic techniques that practice the resect and discard strategy. The aims of this study were to evaluate whether our newly developed real-time image recognition system can predict histologic diagnoses of colorectal lesions depicted on narrow-band imaging and to satisfy some problems with the PIVI recommendations. METHODS: We enrolled 41 patients who had undergone endoscopic resection of 118 colorectal lesions (45 nonneoplastic lesions and 73 neoplastic lesions). We compared the results of real-time image recognition system analysis with that of narrow-band imaging diagnosis and evaluated the correlation between image analysis and the pathological results. RESULTS: Concordance between the endoscopic diagnosis and diagnosis by a real-time image recognition system with a support vector machine output value was 97.5% (115/118). Accuracy between the histologic findings of diminutive colorectal lesions (polyps) and diagnosis by a real-time image recognition system with a support vector machine output value was 93.2% (sensitivity, 93.0%; specificity, 93.3%; positive predictive value (PPV), 93.0%; and negative predictive value, 93.3%). CONCLUSIONS: Although further investigation is necessary to establish our computer-aided diagnosis system, this real-time image recognition system may satisfy the PIVI recommendations and be useful for predicting the histology of colorectal tumors. PMID- 26264432 TI - Electrosurgery in gastrointestinal endoscopy: terminology matters. PMID- 26264433 TI - Underwater endoscopic mucosal resection of a duodenal neuroendocrine tumor. PMID- 26264434 TI - A novel technique for salvaging a dislodged lumen-apposing metal stent during creation of an endoscopic gastrojejunostomy. PMID- 26264435 TI - Use of polidocanol in colon polypectomy. PMID- 26264436 TI - Cyst fluid: moving beyond the carcinoembryonic antigen. PMID- 26264437 TI - Biallelic RFX6 mutations can cause childhood as well as neonatal onset diabetes mellitus. AB - Neonatal diabetes is a highly genetically heterogeneous disorder. There are over 20 distinct syndromic and non-syndromic forms, including dominant, recessive and X-linked subtypes. Biallelic truncating or mis-sense mutations in the DNA-binding domain of the RFX6 transcription factor cause an autosomal recessive, syndromic form of neonatal diabetes previously described as Mitchell-Riley syndrome. In all, eight cases have been reported, with the age at onset of diabetes in the first 2 weeks of life. Here we report two individuals born to double first cousins in whom intestinal atresias consistent with a diagnosis of Mitchell-Riley syndrome were diagnosed at birth, but in whom diabetes did not present until the ages of 3 and 6 years. Novel compound heterozygous RFX6 nonsense mutations (p.Arg726X/p.Arg866X) were identified at the 3' end of the gene. The later onset of diabetes in these patients may be due to incomplete inactivation of RFX6. Genetic testing for RFX6 mutations should be considered in patients presenting with intestinal atresias in the absence of neonatal diabetes. PMID- 26264438 TI - Search for new loci and low-frequency variants influencing glioma risk by exome array analysis. AB - To identify protein-altering variants (PAVs) for glioma, we analysed Illumina HumanExome BeadChip exome-array data on 1882 glioma cases and 8079 controls from three independent European populations. In addition to single-variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally there was a strong relationship between effect size and PAVs predicted to be damaging (P=2.29 * 10(-49)); however, these variants which are most likely to impact on risk, are rare (MAF<5%). Although no single variant showed an association which was statistically significant at the genome-wide threshold a number represented promising associations - BRCA2:c.9976A>T, p.(Lys3326Ter), which has been shown to influence breast and lung cancer risk (odds ratio (OR)=2.3, P=4.00 * 10(-4) for glioblastoma (GBM)) and IDH2:c.782G>A, p.(Arg261His) (OR=3.21, P=7.67 * 10(-3), for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20 * 10(-6)). Genome scans of low-frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power. PMID- 26264439 TI - How communication of genetic information within the family is addressed in genetic counselling: a systematic review of research evidence. AB - Supporting consultands to communicate risk information with their relatives is key to obtaining the full benefits of genetic health care. To understand how health-care professionals address this issue in clinical practice and what interventions are used specifically to assist consultands in their communication of genetic information to appropriate relatives, we conducted a systematic review. Four electronic databases and four subject-specific journals were searched for papers published, in English, between January 1997 and May 2014. Of 2926 papers identified initially, 14 papers met the inclusion criteria for the review and were heterogeneous in design, setting and methods. Thematic data analysis has shown that dissemination of information within families is actively encouraged and supported by professionals. Three overarching themes emerged: (1) direct contact from genetic services: sending letters to relatives of mutation carriers; (2) professionals' encouragement of initially reluctant consultands to share relevant information with at-risk relatives and (3) assisting consultands in communicating genetic information to their at-risk relatives, which included as subthemes (i) psychoeducational guidance and (ii) written information aids. Findings suggest that professionals' practice and interventions are predicated on the need to proactively encourage family communication. We discuss this in the context of what guidance of consultands by professionals might be appropriate, as best practices to facilitate family communication, and of the limits to non directiveness in genetic counselling. PMID- 26264440 TI - Plakophilin-2 c.419C>T and risk of heart failure and arrhythmias in the general population. AB - A rare genetic variant in the desmosomal gene plakophilin-2 (PKP2) c.419C>T(p.(S140F)) has repeatedly been identified in patients with dilated cardiomyopathy (DCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC). Whether this is a disease-causing variant remains highly controversial. We tested this hypothesis using three approaches. Initially, in a prospective study of 10 407 individuals from the general population, including 2688 who developed heart failure or arrhythmias during >14 years of follow-up, PKP2 c.419C>T was identified in 98 individuals (0.94%). PKP2 genotype was not associated with electrocardiographic or echocardiographic changes, or with plasma levels of probrain natriuretic peptide (all P>=0.05). In c.419C>T carriers versus non carriers, multifactorially adjusted hazard ratios were 1.26 (95% confidence interval: 0.77-2.07) for heart failure, 1.40 (0.90-2.17) for arrhythmias, 1.15 (0.78-1.71) for end points combined, and 1.33 (0.98-1.80) for all-cause mortality. The cumulative survival as a function of age and PKP2 genotype was similar among carriers and non-carriers (P=0.14). Second, comparing 517 patients referred for genetic testing with 1918 matched controls, odds ratios as a function of c.419C>T genotype were 2.11 (0.50-8.99) for ARVC, 0.72 (0.16-3.28) for hypertrophic cardiomyopathy (HCM)/DCM, and 1.28 (0.46-3.54) for end points combined. Third, in in vitro studies cellular localization of plakophilin-2, plakoglobin, connexin-43, or N-cadherin were similar in cells transfected with wild-type or mutant plakophilin-2. In conclusion, combining epidemiological data, with data on patients referred for genetic testing for ARVC or HCM/DCM, and data from in vitro studies, PKP2 c.419C>T did not associate with heart failure, arrhythmias, or premature death, with ARVC or HCM/DCM, or with effects in vitro, suggesting that this is not a disease-causing variant. PMID- 26264441 TI - The circadian Clock gene regulates acrosin activity of sperm through serine protease inhibitor A3K. AB - Our previous study found that CLOCK knockdown in the testes of male mice led to a reduced fertility, which might be associated with the lower acrosin activity. In this present study, we examined the differential expression in proteins of CLOCK knockdown sperm. Clock gene expression was knocked down in cells to confirm those differentially expressions and serine protease inhibitor SERPINA3K was identified as a potential target. The up-regulated SERPINA3K revealed an inverse relationship with Clock knockdown. Direct treatment of normal sperm with recombinant SERPINA3K protein inhibited the acrosin activity and reduced in vitro fertilization rate. The luciferase reporter gene assay showed that the down regulated of Clock gene could activate the Serpina3k promoter, but this activation was not affected by the mutation of E-box core sequence. Co-IP demonstrated a natural interaction between SERPIAN3K and RORs (alpha and beta). Taken together, these results demonstrated that SERPINA3K is involved in the Clock gene-mediated male fertility by regulating acrosin activity and provide the first evidence that SERPINA3K could be regulated by Clock gene via retinoic acid related orphan receptor response elements. PMID- 26264443 TI - Phosphatase and tensin homolog deleted on chromosome 10 contributes to phenotype transformation of fibroblasts in idiopathic pulmonary fibrosis via multiple pathways. AB - Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease and considered as a cancer-like disease. The phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor has drawn attention in the pathogenesis of IPF. However, the role of PTEN in phenotypic transformation of lung fibroblasts, particularly in the migratory and invasive phenotype, is still elusive. Our data showed that PTEN expression was markedly reduced in both fibroblasts and myofibroblasts from IPF patients. Furthermore, loss of PTEN led to the transformation of normal fibroblasts to myofibroblasts and increased proliferation, apoptosis resistance, and migration/invasion activities. PTEN deficiency upregulated hyaluronan synthase 2 expression and thereby enhanced the invasion ability of fibroblasts. Cross-talk between PTEN and the transforming growth factor beta1 (TGF-beta1) pathway and PTEN reduction by hypoxia were observed. These findings suggest that PTEN is implicated in multiple pathways and plays a crucial role in the pathogenesis of IPF. PMID- 26264442 TI - The neuronal porosome complex in health and disease. AB - Cup-shaped secretory portals at the cell plasma membrane called porosomes mediate the precision release of intravesicular material from cells. Membrane-bound secretory vesicles transiently dock and fuse at the base of porosomes facing the cytosol to expel pressurized intravesicular contents from the cell during secretion. The structure, isolation, composition, and functional reconstitution of the neuronal porosome complex have greatly progressed, providing a molecular understanding of its function in health and disease. Neuronal porosomes are 15 nm cup-shaped lipoprotein structures composed of nearly 40 proteins, compared to the 120 nm nuclear pore complex composed of >500 protein molecules. Membrane proteins compose the porosome complex, making it practically impossible to solve its atomic structure. However, atomic force microscopy and small-angle X-ray solution scattering studies have provided three-dimensional structural details of the native neuronal porosome at sub-nanometer resolution, providing insights into the molecular mechanism of its function. The participation of several porosome proteins previously implicated in neurotransmission and neurological disorders, further attest to the crosstalk between porosome proteins and their coordinated involvement in release of neurotransmitter at the synapse. PMID- 26264444 TI - A new heterologous fibrin sealant as a scaffold to cartilage repair-Experimental study and preliminary results. AB - Autologous fibrin gel is commonly used as a scaffold for filling defects in articular cartilage. This biomaterial can also be used as a sealant to control small hemorrhages and is especially helpful in situations where tissue reparation capacity is limited. In particular, fibrin can act as a scaffold for various cell types because it can accommodate cell migration, differentiation, and proliferation. Despite knowledge of the advantages of this biomaterial and mastery of the techniques required for its application, the durability of several types of sealant at the site of injury remains questionable. Due to the importance of such data for evaluating the quality and efficiency of fibrin gel formulations on its use as a scaffold, this study sought to analyze the heterologous fibrin sealant developed from the venom of Crotalus durissus terrificus using studies in ovine experimental models. The fibrin gel developed from the venom of this snake was shown to act as a safe, stable, and durable scaffold for up to seven days, without causing adverse side effects. Fibrin gel produced from the venom of the Crotalus durissus terrificus snake possesses many clinical and surgical uses. It presents the potential to be used as a biomaterial to help repair skin lesions or control bleeding, and it may also be used as a scaffold when applied together with various cell types. The intralesional use of the fibrin gel from the venom of this snake may improve surgical and clinical treatments in addition to being inexpensive and adequately consistent, durable, and stable. The new heterologous fibrin sealant is a scaffold candidate to cartilage repair in this study. PMID- 26264445 TI - Decitabine enhances stem cell antigen-1 expression in cigarette smoke extract induced emphysema in animal model. AB - Stem cell antigen-1 (Sca-1) is a mouse glycosyl phosphatidylinositol-anchored protein and a cell surface marker found on hematopoietic stem cells (HSCs). Despite decades of study, its biological functions remain little known. Sca-1 is a typical marker of bone marrow-derived HSCs, it is also expressed by a mixture of tissue-resident stem, progenitor cells in nonhematopoietic organs. Endothelial progenitor cell (EPC) is a subtype of HSC and contributes to endothelial repair by homing in on locations of injury. Abnormal genetic methylation has been detected in smoking-related diseases. The present study aimed to investigate the lung function and histomorphology, the expression of Sca-1 gene in lung tissues, and bone marrow-derived EPCs in cigarette smoke extract (CSE)-induced emphysema mice, and to further determine whether Decitabine (Dec), the most widely used inhibitor of DNA methylation, could protect against the damages caused by CSE. The results of the present study demonstrated that Dec could partly protect against CSE-induced emphysema in mice, enhance Sca-1 expression in lung tissue, and bone marrow-derived EPCs. The results suggested that the depletion of the progenitor cell pool and DNA methylation of Sca-1 gene may be involved in the progression of emphysema in mice. PMID- 26264446 TI - Increased breast cancer screening and downstaging in Colombian women: A randomized trial of opportunistic breast-screening. AB - The lack of breast cancer screening in low and middle-income countries results in later stage diagnosis and worsened outcomes for women. A cluster randomized trial was performed in Bogota, Colombia between 2008 and 2012 to evaluate effects of opportunistic breast cancer screening. Thirteen clinics were randomized to an intervention arm and 13 to a control arm. Physicians in intervention clinics were instructed to perform clinical breast examination on all women aged 50-69 years attending clinics for non-breast health issues, and then refer them for mammographic screening. Physicians in control clinics were not explicitly instructed to perform breast screening or mammography referrals, but could do so if they thought it indicated ("usual care"). Women were followed for 2-years postrandomization. 7,436 women were enrolled and 7,419 (99.8%) screened in intervention clinics, versus 8,419 enrolled and 1,108 (13.1%) screened in control clinics. Incidence ratios (IR) of early, advanced and all breast cancers were 2.9 (95% CI 1.1-9.2), 1.0 (0.3-3.5) and 1.9 (0.9-4.1) in the first (screening) year of the trial, and the cumulative IR for all breast cancers converged to 1.4 (0.7 2.8) by the end of follow-up (Year 2). Eighteen (69.2%) of 26 women with early stage disease had breast conservation surgery (BCS) versus 6 (42.5%) of 14 women with late-stage disease (p = 0.02). Fifteen (68.2%) of 22 women with breast cancer in the intervention group had BCS versus nine (50.0%) of 18 women in the control group (p = 0.34). Well-designed opportunistic clinic-based breast cancer screening programs may be useful for early breast cancer detection in LMICs. PMID- 26264447 TI - Quantifying spatial habitat loss from hydrocarbon development through assessing habitat selection patterns of mule deer. AB - Extraction of oil and natural gas (hydrocarbons) from shale is increasing rapidly in North America, with documented impacts to native species and ecosystems. With shale oil and gas resources on nearly every continent, this development is set to become a major driver of global land-use change. It is increasingly critical to quantify spatial habitat loss driven by this development to implement effective mitigation strategies and develop habitat offsets. Habitat selection is a fundamental ecological process, influencing both individual fitness and population-level distribution on the landscape. Examinations of habitat selection provide a natural means for understanding spatial impacts. We examined the impact of natural gas development on habitat selection patterns of mule deer on their winter range in Colorado. We fit resource selection functions in a Bayesian hierarchical framework, with habitat availability defined using a movement-based modeling approach. Energy development drove considerable alterations to deer habitat selection patterns, with the most substantial impacts manifested as avoidance of well pads with active drilling to a distance of at least 800 m. Deer displayed more nuanced responses to other infrastructure, avoiding pads with active production and roads to a greater degree during the day than night. In aggregate, these responses equate to alteration of behavior by human development in over 50% of the critical winter range in our study area during the day and over 25% at night. Compared to other regions, the topographic and vegetative diversity in the study area appear to provide refugia that allow deer to behaviorally mediate some of the impacts of development. This study, and the methods we employed, provides a template for quantifying spatial take by industrial activities in natural areas and the results offer guidance for policy makers, mangers, and industry when attempting to mitigate habitat loss due to energy development. PMID- 26264448 TI - Vaping cannabis (marijuana): parallel concerns to e-cigs? AB - The proliferation of vaporization ('vaping') as a method for administering cannabis raises many of the same public health issues being debated and investigated in relation to e-cigarettes (e-cigs). Good epidemiological data on the prevalence of vaping cannabis are not yet available, but with current trends towards societal approval of medicinal and recreational use of cannabis, the pros and cons of vaping cannabis warrant study. As with e-cigs, vaping cannabis portends putative health benefits by reducing harm from ingesting toxic smoke. Indeed, vaping is perceived and being sold as a safer way to use cannabis, despite the lack of data on the health effects of chronic vaping. Other perceived benefits include better taste, more efficient and intense effects and greater discretion which allows for use in more places. Unfortunately, these aspects of vaping could prompt an increased likelihood of trying cannabis, earlier age of onset, more positive initial experiences, and more frequent use, thereby increasing the probability of problematic use or addiction. Sales and marketing of vaping devices with no regulatory guidelines, especially related to advertising or product development targeting youth, parallels concerns under debate related to e-cigs and youth. Thus, the quandary of whether or not to promote vaping as a safer method of cannabis administration for those wishing to use cannabis, and how to regulate vaping and vaping devices, necessitates substantial investigation and discussion. Addressing these issues in concert with efforts directed towards e-cigs may save time and energy and result in a more comprehensive and effective public health policy on vaping. PMID- 26264449 TI - Drug-induced immune hemolytic anemia associated with anti-carboplatin and the first example of anti-paclitaxel. AB - BACKGROUND: Combined chemotherapy with carboplatin and paclitaxel is first-line treatment for lung and ovarian cancer. Drug-induced antibodies to carboplatin are rare but can cause severe, even fatal, hemolysis. Paclitaxel-induced immune hemolysis has not been reported. We describe a case of immune-mediated hemolysis associated with antibodies to carboplatin and paclitaxel in a woman with ovarian cancer who had received multiple chemotherapeutic agents over 7 years, including several courses of these two drugs. She required many transfusions. During a chemotherapy infusion the patient became hypotensive, was pale, and had rigors and red urine. The nadir hematocrit was 12.4%; peak bilirubin and lactate dehydrogenase were 16.3 mg/dL and 1188 units/L, respectively. STUDY DESIGN AND METHODS: Blood samples collected within hours after chemotherapy and 2 days later were tested for antibodies to carboplatin and paclitaxel. RESULTS: The direct antiglobulin test was positive with anti-IgG (3+) and anti-C3 (2+). The plasma collected shortly after chemotherapy agglutinated carboplatin-treated red blood cells (RBCs); untreated and paclitaxel-treated RBCs both reacted at the antiglobulin test most likely due to circulating carboplatin, paclitaxel, or both drugs. Serum collected 2 days later agglutinated (titer 2) and sensitized (titer 128) carboplatin-treated RBCs; untreated and paclitaxel-treated RBCs were nonreactive. An acid eluate reacted weakly in the presence of polyethylene glycol with carboplatin-treated RBCs. The serum reacted with untreated and enzyme treated RBCs in the presence of soluble carboplatin and paclitaxel. CONCLUSION: Anti-carboplatin and the first example of anti-paclitaxel were detected in this patient's sample. PMID- 26264450 TI - Risk factors associated with lambing traits. AB - The objective of this study was to establish the risk factors associated with both lambing difficulty and lamb mortality in the Irish sheep multibreed population. A total of 135 470 lambing events from 42 675 ewes in 839 Irish crossbred and purebred flocks were available. Risk factors associated with producer-scored ewe lambing difficulty score (scale of one (no difficulty) to four (severe difficulty)) were determined using linear mixed models. Risk factors associated with the logit of the probability of lamb mortality at birth (i.e. binary trait) were determined using generalised estimating equations. For each dependent variable, a series of simple regression models were developed as well as a multiple regression model. In the simple regression models, greater lambing difficulty was associated with quadruplet bearing, younger ewes, of terminal breed origin, lambing in February; for example, first parity ewes experienced greater (P7.0 kg) birth weights, quadruplet born lambs and lambs that experienced a more difficult lambing (predicted probability of death for lambs that required severe and veterinary assistance of 0.15 and 0.32, respectively); lambs from dual purpose breeds and born to younger ewes were also at greater risk of mortality. In the multiple regression model, the association between ewe parity, age at first lambing, year of lambing and lamb mortality no longer persisted. The trend in solutions of the levels of each fixed effect that remained associated with lamb mortality in the multiple regression model, did not differ from the trends observed in the simple regression models although the differential in relative risk between the different lambing difficulty scores was greater in the multiple regression model. Results from this study show that many common flock- and animal level factors are associated with both lambing difficulty and lamb mortality and management of different risk category groups (e.g. scanned litter sizes, ewe age groups) can be used to appropriately manage the flock at lambing to reduce their incidence. PMID- 26264451 TI - A Review of Diabetes Mellitus and Exposure to the Environmental Toxicant Cadmium with an Emphasis on Likely Mechanisms of Action. AB - There is increasing interest in how exposure to environmental substances can contribute to the onset of Type II diabetes mellitus (T2DM). Impaired insulin release is a hallmark of type I diabetes mellitus and is involved in the progression of T2DM. Both epidemiological and experimental studies show that exposure to the environmental pollutant cadmium (Cd), is associated with hyperglycemia, T2DM and reduced serum insulin. The goal of this review is to examine likely mechanisms of action of Cd-induced dysglycemia based on experimental studies in the literature and from the most recent findings in the Edwards lab. The primary focus of this review will examine how Cd may cause islet dysfunction and subsequent impaired insulin release. Recent findings in the Edwards lab indicate that Cd causes timedependent and statistically significant changes in fasting leptin, Glucose-dependent Insulinotropic Polypeptide (GIP) and pancreas polypeptide hormone levels in a subchronic animal model of Cd-induced hyperglycemia. This review summarizes the most likely cellular mechanisms by which the ubiquitous environmental contaminant Cd disrupts glucose homeostasis. While individual cellular effects of Cd are reviewed it is likely that no one single mechanism is involved, rather multiple mechanisms exist and work synergistically resulting in islet dysfunction and ultimately dysglycemia. PMID- 26264452 TI - Liver transplant recipients and prioritization of anti-HCV therapy: an Italian cohort analysis. AB - BACKGROUND AND AIMS: In patients with hepatitis C virus (HCV), recurrence of infection after liver transplant (LT) is universal and associated with worst survival. We present the results of an Italian cohort to compare the 3-year outcome of HCV-Ab-positive and HCV-Ab-negative LT recipients and to assess the potential interaction between HCV-Ab sero-status and other risk factors for LT failure. METHODS: The study is a multicentre cohort including a sample of liver transplant centres. Participant's information was collected at the local level. The best functional form of variables was decided according to the objective methods based on information theory. Association between transplant failure and potential risk factors was assessed in univariate and multivariate Poisson regression model with random intercept. RESULTS: Between June 2007 and May 2009, 1164 LT recipients were enrolled in 16 Italian transplant centres, of them 275 (23.63%) experienced LT failure. Incidence rates of LT failure was 0.32 and 0.23 per 1000 person-days in HCV-Ab-positive and HCV-Ab-negative recipients respectively (P = 0.003). Inferential models according to Akaike information criterion indicated that donor-recipient age difference and donor-recipient sex matching were more informative to predict LT failure than the age and the sex as separate variables. Multivariate analysis provided evidence that HCV-Ab sero status, time after LT, donor-recipient age difference, donor-recipient sex matching and recipient's MELD score were significantly associated with LT failure. Moreover, the effect of HCV-Ab sero-status on LT failure was modified by the simultaneous action of time after LT and donor-recipient age difference. No interaction was found between recipient's HCV-Ab sero-status and either recipient's MELD or donor-recipient sex matching. CONCLUSION: In view of the imminent introduction of new anti-HCV therapies, our study provides information to assess which LT recipients should be prioritized for receiving these highly effective, but expensive, new treatments. This is particularly relevant for those clinical settings where healthcare prioritization is endorsed by national authorities. PMID- 26264453 TI - Developing educational competencies for dissemination and implementation research training programs: an exploratory analysis using card sorts. AB - BACKGROUND: With demand increasing for dissemination and implementation (D&I) training programs in the USA and other countries, more structured, competency based, and tested curricula are needed to guide training programs. There are many benefits to the use of competencies in practice-based education such as the establishment of rigorous standards as well as providing an additional metrics for development and growth. As the first aim of a D&I training grant, an exploratory study was conducted to establish a new set of D&I competencies to guide training in D&I research. METHODS: Based upon existing D&I training literature, the leadership team compiled an initial list of competencies. The research team then engaged 16 additional colleagues in the area of D&I science to provide suggestions to the initial list. The competency list was then additionally narrowed to 43 unique competencies following feedback elicited from these D&I researchers. Three hundred additional D&I researchers were then invited via email to complete a card sort in which the list of competencies were sorted into three categories of experience levels. Participants had previous first-hand experience with D&I or knowledge translation training programs in the past. Participants reported their self-identified D&I expertise level as well as the country in which their home institution is located. A mean score was calculated for each competency based on their experience level categorization. From these mean scores, beginner-, intermediate-, and advanced-level tertiles were created for the competencies. RESULTS: The card sort request achieved a 41 % response rate (n = 124). The list of 43 competencies was organized into four broad domains and sorted based on their experience level score. Eleven competencies were classified into the "Beginner" category, 27 into "Intermediate," and 5 into "Advanced." CONCLUSIONS: Education and training developers can use this competency list to formalize future trainings in D&I research, create more evidence-informed curricula, and enable overall capacity building and accompanying metrics in the field of D&I training and research. PMID- 26264454 TI - Hip range-of-motion (ROM) is less than normal after rotational acetabular osteotomy for developmental dysplasia of the hip: A simulated ROM analysis. AB - The optimal reorientation of the acetabulum for developmental dysplasia of the hip (DDH) is unknown in terms of hip range-of-motion (ROM). The simulated ROMs of 52 DDHs after rotational acetabular osteotomy (RAO) with several patterns of femoral head coverage and those of 73 normal hips were analyzed using computer models reconstructed from CT images. After RAO with a lateral center edge angle (LCEA) of 30 degrees and an anterior center edge angle (ACEA) of 55 degrees producing coverage similar to that of normal hips, the maximal flexion and maximal internal rotation at 110 degrees flexion with 20 degrees adduction were significantly smaller than those of the normal group. To achieve ROMs after RAO similar to those of the normal group, an LCEA of 30 degrees with an ACEA of 45 degrees , an LCEA of 25 degrees with an ACEA of 45 degrees to 50 degrees , and an LCEA of 20 degrees with an ACEA of 50 degrees could be preferred angles to target, even though they provided smaller coverage than that of normal hips. After RAO producing femoral head coverage similar to that of normal hips, the maximal flexion and the maximal internal rotation at 110 degrees flexion with 20 degrees adduction were significantly smaller than those of the normal group. PMID- 26264455 TI - Faecal microbiota transplant for recurrent Clostridium difficile infection using long-term frozen stool is effective: clinical efficacy and bacterial viability data. AB - BACKGROUND: Faecal microbial transplant (FMT) for recurrent Clostridium difficile infection (rCDI) is greatly facilitated by frozen stool banks. However, the effect of frozen storage of stool for greater than 2 months on the viability of stool bacteria is unknown and the efficacy of FMT is not clear. AIM: To evaluate the viability of bacteria in stool frozen for up to 6 months, and the clinical efficacy of FMT with stool frozen for 2-10 months, for the treatment of rCDI. METHODS: Viability of six representative groups of faecal bacteria after 2 and 6 months of storage at -80 degrees C, in normal saline (NS) or 10% glycerol were assessed by culture on plate media. The clinical outcomes of 16 consecutive patients with rCDI treated with aliquots of stool frozen in 10% glycerol and stored for 2-10 months were also examined. RESULTS: Viability at both 2 and 6 months was similar to baseline, in specimens stored in 10% glycerol and at 2 months in stool stored in NS, but was reduced by >1 log at 6 months for Aerobes (P < 0.01), total Coliforms (P < 0.01) and Lactobacilli (P < 0.01) in NS. Using stool frozen for 2-10 months in 10% glycerol, the cure rate for rCDI was 88% with one FMT and 100% after repeat FMT in those who relapsed. CONCLUSION: Stool for faecal microbial transplant to treat rCDI can be safely stored frozen in 10% glycerol for at least 6 months without loss of clinical efficacy or viability in the six bacterial groups tested. PMID- 26264456 TI - Scrub Typhus (Tsutsugamushi Disease) Presenting as Fever with an Eschar. PMID- 26264457 TI - Improving maternal nutrition for better pregnancy outcomes. AB - Much has been learned during the past several decades about the role of maternal nutrition in the outcome of pregnancy. While the bulk of the data is derived from animal models, human observations are gradually accumulating. There is need to improve maternal nutrition because of the high neonatal mortality rate especially in developing countries. The author used a conceptual framework which took both primary and secondary factors into account when interpreting study findings. Nutrition plays a vital role in reducing some of the health risks associated with pregnancy such as risk of fetal and infant mortality, intra-uterine growth retardation, low birth weight and premature births, decreased birth defects, cretinism, poor brain development and risk of infection. Adequate nutrition is essential for a woman throughout her life cycle to ensure proper development and prepare the reproductive life of the woman. Pregnant women require varied diets and increased nutrient intake to cope with the extra needs during pregnancy. Use of dietary supplements and fortified foods should be encouraged for pregnant women to ensure adequate supply of nutrients for both mother and foetus. The author concludes that nutrition education should be a core component of Mother and Child Health Clinics and every opportunity should be utilised to give nutrition education on appropriate diets for pregnant women. PMID- 26264459 TI - Letter to the Editor: Essential Surgery: The Way Forward. PMID- 26264458 TI - Changes in the Surgical Management of Parastomal Hernias Over 15 Years: Results of 135 Cases. AB - BACKGROUND: Over the years, various open and laparoscopic approaches toward the repair of parastomal hernias (PSH) have been described. The variety of published techniques itself can be seen as an indicator for the often low level of satisfaction reached with the surgical procedures. METHODS: From January 1999 to January 2014, we assessed all cases of PSH repair performed at the three participating surgical departments in a retrospective analysis. The results were evaluated with regard to different surgical techniques focusing on complications and recurrences. RESULTS: One hundred and thirty-five individuals could be included in the analysis. They were operated on with eight different surgical techniques. Laparoscopic procedures were carried out in 46.7 % (63/135) of the cases. Median follow-up was 54 months (12-146 months). We found 44 cases of recurrence (32.6 %) and 24 (17.8 %) of the patients experienced perioperative complications and 12 of them needed to return to theater. Fourteen of the 135 patients (10.4 %) were operated as emergency cases which were associated with a mortality of 28.6 % (4/14). In case of elective PSH repair, no mortality occured. CONCLUSION: The results achieved by direct suture or the use of incised flat meshes for the repair of PSH were poor with these procedures having unacceptably high recurrence rates. With regard to the latter ostomy revision through three dimensional funnel-shaped meshes and the laparoscopic sandwich technique showed the best results. Emergency procedures were linked to a dramatic increase in morbidity and mortality (p < 0.001). PMID- 26264460 TI - Expanding the Molecular and Clinical Phenotype of SSR4-CDG. AB - Congenital disorders of glycosylation (CDG) are a group of mostly autosomal recessive disorders primarily characterized by neurological abnormalities. Recently, we described a single CDG patient with a de novo mutation in the X linked gene, Signal Sequence Receptor 4 (SSR4). We performed whole-exome sequencing to identify causal variants in several affected individuals who had either an undifferentiated neurological disorder or unsolved CDG of unknown etiology based on abnormal transferrin glycosylation. We now report eight affected males with either de novo (4) or inherited (4) loss of function mutations in SSR4. Western blot analysis revealed that the mutations caused a complete loss of SSR4 protein. In nearly all cases, the abnormal glycosylation of serum transferrin was only slightly above the accepted normal cutoff range. PMID- 26264461 TI - Involvement of Rho-associated protein kinase (ROCK) and bone morphogenetic protein-binding endothelial cell precursor-derived regulator (BMPER) in high glucose-increased alkaline phosphatase expression and activity in human coronary artery smooth muscle cells. AB - BACKGROUND: Vascular calcification is an independent risk factor for cardiovascular disease. Diabetes mellitus increases the incidence of vascular calcification; however, detailed molecular mechanisms of vascular calcification in diabetes mellitus remain unknown. We recently reported that bone morphogenetic protein-binding endothelial cell precursor-derived regulator (BMPER) regulates osteoblast-like trans-differentiation of human coronary artery smooth muscle cells (HCASMCs). METHODS: We investigated the effect of a hydroxymethylglutaryl coenzyme A reductase inhibitor (statin), commonly used in patients with atherosclerotic diseases and diabetes mellitus, on alkaline phosphatase (ALP) mRNA expression in aortas of streptozotocin-induced diabetic mice. We also investigated the effects of the statin, Rho-associated protein kinase (ROCK) inhibitors and BMPER knockdown on ALP mRNA expression and activity in HCASMCs cultured in high glucose-containing media. RESULTS: Alkaline phosphatase mRNA expression was increased in aortas of streptozotocin-induced diabetic mice, and the increase was inhibited by rosuvastatin. ALP mRNA expression and activity were increased in HCASMCs cultured in high glucose-containing media, and the increases were suppressed by rosuvastatin. This suppression was reversed by the addition of mevalonate or geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate. High glucose-increased ALP mRNA expression and activity were suppressed by ROCK inhibitors. Moreover, BMPER mRNA expression was increased in diabetic mouse aortas and in HCASMCs cultured in high glucose-containing media, but was not inhibited by rosuvastatin or ROCK inhibitors. Knockdown of BMPER suppressed high glucose-increased ALP activity, but not ROCK activity in HCASMCs. CONCLUSIONS: There are at least two independent pathways in high glucose-induced ALP activation in HCASMCs: the Rho-ROCK signaling pathway and the BMPER-dependent pathway. PMID- 26264463 TI - An unusual cause of overt gastrointestinal bleeding in a malnourished child. AB - Trichuris trichiura (T. Trichiura) is a known parasite infestation among tropical children. Humans acquire Trichuriasis infection after ingestion of embryonated eggs via contaminated food or water. Most of them are asymptomatic. A severe form of trichuris infestation is known as Trichuris dysentery syndrome (TDS). It manifests as mucous diarrhoea, bleeding, malnutrition and stunting, or even life threatening anaemia. We are reporting an interesting case of a 7-year-old girl who presented with bloody diarrhoea for 2 years. Her growth was stunted as she was not gaining weight. Severe inflammatory bowel disease was suspected clinically. Physical examination revealed marked pallor, pedal oedema and koilonychia along with sparse and hypopigmented hair. On evaluationT. Trichiurahelminths were seen on stool examination and massive worm load was visualised directly on colonoscopy. A diagnosis of TDS was made. She was successfully treated with oral Albendazole (400 mg) and blood transfusion. PMID- 26264462 TI - Expression of miR-296-5p as predictive marker for radiotherapy resistance in early-stage laryngeal carcinoma. AB - PURPOSE: Definitive radiation therapy is the mainstay of treatment for early stage laryngeal squamous cell carcinoma (LSCC). However, up to 30% of the patients do not respond to radiotherapy. Unfortunately, we are unable to predict which tumors are likely to respond to radiation, and which will be resistant and persist. Therefore, the development of novel markers to predict response to radiotherapy is urgently needed. This study was designed to evaluate the expression pattern of microRNAs (miRNAs) in LSCC in order to identify markers capable of segregating radioresistant and radiosensitive tumors and to investigate the relationship between the expression of these miRNAs and the prognosis of LSCC. METHODS: The expression profile of 667 miRNAs was determined in an initial screening of nine early-stage LSCC samples (5 radioresistant and 4 radiosensitive) using TaqMan Low-Density Array (TLDA). Real-time polymerase chain reactions were performed to validate the expression of selected miRNAs in an expanded LSCC cohort (20 radioresistant and 14 radiosensitive). The miRNA expression level was scored as high or low based on the median of the expression in the LSCC samples. RESULTS: A comprehensive miRNA expression profiling enabled the identification of four miRNAs (miR-296-5p miR-452, miR-183* and miR-200c) differentially expressed in radioresistant LSCC. Moreover, the analysis of additional 34 LSCC samples, confirmed the expression of miR-296-5p as significantly related to radioresistance (p = 0.002) as well as an association of this marker with recurrence (p = 0.025) in early stage laryngeal cancer. CONCLUSIONS: This study indicates that miR-296-5p expression is associated with resistance to radiotherapy and tumor recurrence in early stage LSCC, showing the feasibility of this marker as a novel prognostic factor for this malignance. Furthermore, miR-296-5p expression could be helpful in the identification of tumors resistant to radiotherapy; thus aiding the clinicians in the choice of the best therapeutic scheme to be used in each case. PMID- 26264464 TI - 'Splitting versus lumping': Temple-Baraitser and Zimmermann-Laband Syndromes. AB - KCNH1 mutations have recently been described in six individuals with Temple Baraitser syndrome (TMBTS) and six individuals with Zimmermann-Laband syndrome (ZLS). TMBTS is characterized by intellectual disability (ID), epilepsy, dysmorphic facial features, broad thumbs and great toes with absent/hypoplastic nails. ZLS is characterized by facial dysmorphism including coarsening of the face and a large nose, gingival enlargement, ID, hypoplasia of terminal phalanges and nails and hypertrichosis. In this study, we present four additional unrelated individuals with de novo KCNH1 mutations from ID cohorts. We report on a novel recurrent pathogenic KCNH1 variant in three individuals and add a fourth individual with a previously TMBTS-associated KCNH1 variant. Neither TMBTS nor ZLS was suspected clinically. KCNH1 encodes a voltage-gated potassium channel, which is not only highly expressed in the central nervous system, but also seems to play an important role during development. Clinical evaluation of our mutation positive individuals revealed that one of the main characteristics of TMBTS/ZLS, namely the pronounced nail hypoplasia of the great toes and thumbs, can be mild and develop over time. Clinical comparison of all published KCNH1 mutation positive individuals revealed a similar facial but variable limb phenotype. KCNH1 mutation-positive individuals present with severe ID, neonatal hypotonia, hypertelorism, broad nasal tip, wide mouth, nail a/hypoplasia, a proximal implanted and long thumb and long great toes. In summary, we show that the phenotypic variability of individuals with KCNH1 mutations is more pronounced than previously expected, and we discuss whether KCNH1 mutations allow for "lumping" or for "splitting" of TMBTS and ZLS. PMID- 26264465 TI - Factor analyses of an Adult Epilepsy Self-Management Measurement Instrument (AESMMI). AB - The purpose of this study was to test the psychometric properties of an enhanced Adult Epilepsy Self-Management Measurement Instrument (AESMMI). An instrument of 113 items, covering 10 a priori self-management domains, was generated through a multiphase process, based on a review of the literature, validated epilepsy and other chronic condition self-management scales and expert input. Reliability and exploratory factor analyses were conducted on data collected from 422 adults with epilepsy. The instrument was reduced to 65 items, converging on 11 factors: Health-care Communication, Coping, Treatment Management, Seizure Tracking, Social Support, Seizure Response, Wellness, Medication Adherence, Safety, Stress Management, and Proactivity. Exploratory factors supported the construct validity for 6 a priori domains, albeit with significant changes in the retained items or in their scope and 3 new factors. One a priori domain was split in 2 subscales pertaining to treatment. The configuration of the 11 factors provides additional insight into epilepsy self-management behaviors. Internal consistency reliability of the 65-item instrument was high (alpha=.935). Correlations with independent measures of health status, quality of life, depression, seizure severity, and life impact of epilepsy further validated the instrument. This instrument shows potential for use in research and clinical settings and for assessing intervention outcomes and self-management behaviors in adults with epilepsy. PMID- 26264467 TI - Impact of disease management programs on women with breast cancer in Germany. AB - The aim of the study was to analyze the impact of disease management programs (DMPs) on adherence in women with breast cancer (BC) in Germany. Data on 4915 BC patients [1874 DMP and 3041 standard care (SC)] who started hormone therapy between 2008 and 2013 in 234 gynecological practices in Germany were analyzed retrospectively. The primary outcome measure was the rate of discontinuation of hormone therapy within 3 years of the start of treatment. Discontinuation of therapy was defined as a period of at least 90 days without treatment. A multivariate Cox regression model was created to determine the effect of DMPs on the risk of discontinuation. Region (western vs. eastern Germany), patient age, and concomitant diagnoses (depression, osteoporosis, thrombosis, and diabetes) were included as covariates. There was a significant difference between DMPs and SC in terms of age (63 +/- 12 years vs. 64 +/- 12 years, p value = 0.0012) and region (79.2% of patients living in western Germany vs. 88.6%, p value < 0.0001), but not initial therapy (51.8% vs. 52%, p value = 0.8696). Depression was also more common in patients in DMPs than those in SC (26.8% vs. 17.3%, p value < 0.0001). Within 3 years of therapy initiation, 32.7% of DMP patients and 39.6% of SC patients had discontinued their treatment (p < 0.001). Women with BC who were enrolled in a DMP had a lower risk of discontinuing therapy (HR = 0.91, 95% CI: 0.85-0.98, p value = 0.0092). This risk was also slightly higher in western Germany (HR = 1.13, 95% CI: 1.02-1.24, p value = 0.0143). Involvement in DMPs has a positive impact on the adherence of BC patients. PMID- 26264466 TI - Third International Congress on Epilepsy, Brain, and Mind: Part 2. AB - Epilepsy is both a disease of the brain and the mind. Here, we present the second of two papers with extended summaries of selected presentations of the Third International Congress on Epilepsy, Brain and Mind (April 3-5, 2014; Brno, Czech Republic). Humanistic, biologic, and therapeutic aspects of epilepsy, particularly those related to the mind, were discussed. The extended summaries provide current overviews of epilepsy, cognitive impairment, and treatment, including brain functional connectivity and functional organization; juvenile myoclonic epilepsy; cognitive problems in newly diagnosed epilepsy; SUDEP including studies on prevention and involvement of the serotoninergic system; aggression and antiepileptic drugs; body, mind, and brain, including pain, orientation, the "self-location", Gourmand syndrome, and obesity; euphoria, obsessions, and compulsions; and circumstantiality and psychiatric comorbidities. PMID- 26264468 TI - The effects of erythropoiesis-stimulating agents on the short-term and long-term survivals in metastatic breast cancer patients receiving chemotherapy: a SEER population-based study. AB - Current clinical guidelines state that the use of erythropoiesis-stimulating agents (ESAs) may be considered to treat chemotherapy-induced anemia in the non curative setting to alleviate anemia-related symptoms. However, no convincing survival benefit has been demonstrated to support the use of ESAs in these patients. Using the comprehensive data collected in the National Cancer Institute (NCI)-surveillance epidemiology and end results (SEER) and Medicare-linked database, we analyzed the effect of ESA use on the short-term (18-month) and long term (60-month) survival rates of chemotherapy-treated metastatic breast cancer patients. Confounding variables were adjusted using a propensity score approach. We also analyzed the effects of ESA on the survival of patients receiving trastuzumab, a commonly prescribed targeted therapy agent in treating HER2 positive tumors. Metastatic breast cancer patients who received ESA treatment exhibited similar 60-month survival rate to those without ESA treatment (22.8 vs. 24.9%, p = 0.8). ESA-treated patients had a trend toward better 18-month survival [crude hazard ratio (HR) 0.86, 95% confidence intervals (CI) 0.68-1.09, p = 0.21]. This protective effect during the first 18 months of chemotherapy became marginally significant after adjusting for the propensity of receiving ESAs (HR 0.80, 95% CI 0.63-1.01, p = 0.070). An interaction effect between ESA and trastuzumab on patient survival was noticeable but not statistically significant. ESAs did not negatively affect the long-term survival of metastatic breast cancer patients. Moreover, ESAs improved patients' survival during the first 18 months of chemotherapy treatment. These findings endorse the current clinical guideline. Given the short survival of these patients, the potential short-term beneficial effects of ESAs are clinically meaningful. PMID- 26264469 TI - Complex fibroadenoma and breast cancer risk: a Mayo Clinic Benign Breast Disease Cohort Study. AB - The purpose of this study is to examine the breast cancer risk overall among women with simple fibroadenoma or complex fibroadenoma and to examine the association of complex fibroadenoma with breast cancer through stratification of other breast cancer risks. The study included women aged 18-85 years from the Mayo Clinic Benign Breast Disease Cohort who underwent excisional breast biopsy from 1967 through 1991. Within this cohort, women who had fibroadenoma were compared to women who did not have fibroadenoma. Breast cancer risk (observed versus expected) across fibroadenoma levels was assessed through standardized incidence ratios (SIRs) by using age- and calendar-stratified incidence rates from the Iowa Surveillance, Epidemiology, and End Results registry. Analyses were performed overall, within subgroups of involution status, with other demographic characteristics (age, year of biopsy, indication for biopsy, and family history), and with histologic characteristics, including overall impression [nonproliferative disease, proliferative disease without atypia (PDWA), or atypical hyperplasia]. Fibroadenoma was identified in 2136 women [noncomplex, 1835 (85.9%); complex, 301 (14.1%)]. SIR for noncomplex fibroadenoma was 1.49 (95% CI 1.26-1.74); for complex fibroadenoma, it was 2.27 (95% CI 1.63-3.10) (test for heterogeneity in SIR, P = .02). However, women with complex fibroadenoma were more likely to have other, concomitant high-risk histologic characteristics (e.g., incomplete involution and PDWA). In analyses stratified by involution status and PDWA, complex fibroadenoma was not an independent risk marker for breast cancer. Complex fibroadenoma does not confer increased breast cancer risk beyond other established histologic characteristics. PMID- 26264471 TI - Impact of fecal immunochemical test-based screening programs on proximal and distal colorectal cancer surgery rates: A natural multiple-baseline experiment. AB - BACKGROUND: Colorectal cancer (CRC) screening programs based on the fecal immunochemical test (FIT) were found to reduce overall CRC surgery rates, but to the authors' knowledge data by subsite are lacking. The objective of the current study was to assess the impact of FIT-based screening on proximal and distal CRC surgical resection rates. METHODS: The Veneto region in Italy can be subdivided into 3 areas with staggered introduction of FIT-based screening programs: early (2002-2004), intermediate (2005-2007), and late (2008-2009) areas. Time series of proximal and distal CRC surgery were investigated in the 3 populations between 2001 and 2012 by Joinpoint regression analysis and segmented Poisson regression models. RESULTS: The impact of screening was similar in the study populations. Rates of distal CRC surgical resection were stable before screening, increased at the time of screening implementation (rate ratio [RR], 1.25; 95% confidence interval [95% CI], 1.14-1.37), and thereafter declined by 10% annually (RR, 0.90; 95% CI, 0.88-0.92). Rates of proximal CRC surgical resection increased by 4% annually before screening (RR, 1.04; 95% CI, 1.03-1.05) but, after a peak at the time of screening initiation, the trend was reversed. The percentage represented by proximal CRC surgery rose from 28% in 2001 to 41% in 2012. CONCLUSIONS: In this natural multiple-baseline experiment, consistent findings across each time series demonstrated that FIT-based screening programs have an impact both on proximal and distal CRC surgery rates. However, underlying preexisting epidemiological trends are leading to a rapidly increasing percentage of proximal CRC. PMID- 26264470 TI - Which field walking test should be used to assess functional exercise capacity in lung cancer? An observational study. AB - BACKGROUND: There is emerging evidence regarding the efficacy of exercise training to improve exercise capacity for individuals with non-small cell lung cancer (NSCLC). Cardiopulmonary exercise testing (CPET) is the gold standard measure of exercise capacity; however this laboratory test has limitations for use in research and clinical practice. Alternative field walking tests are the six-minute walk test (6MWT), incremental-shuttle walk test (ISWT) and endurance shuttle walk test (ESWT); however there is limited information about their clinimetric properties in NSCLC. AIMS: In NSCLC to determine the 1) criterion validity of the 6MWT, ISWT and ESWT against CPET; 2) construct validity of the 6MWT, ISWT and ESWT against measures of function, strength, respiratory function and health-related quality of life (HRQoL); and 3) clinical applicability of the tests. METHODS: Twenty participants (40 % male, mean +/- SD age 66.1 +/- 6.5 years) with stage I-IIIb NSCLC completed the 6MWT, ISWT, ESWT and CPET within six months of treatment. Testing order was randomised. Additional measures included Eastern Cooperative Oncology Group Performance-Status (ECOG-PS, function), respiratory function, hand-grip dynamometry and HRQoL. Correlations and regression analyses were used to assess relationships. RESULTS: The ISWT demonstrated criterion validity with a moderate relationship between ISWT distance and CPET peak oxygen consumption (r = 0.61, p = 0.007). Relationships between CPET and six minute walk distance (6MWD) (r = 0.24, p = 0.329) or ESWT time (r = 0.02, p = 0.942) were poor. Moderate construct validity existed for the 6MWD and respiratory function (forced vital capacity % predicted r = 0.53, p = 0.019; forced expiratory volume in the first second % predicted r = 0.55, p = 0.015). There were no relationships between the walking tests and measures of function, strength or HRQoL. The ESWT had a ceiling effect with 18 % reaching maximum time. No floor effects were seen in the tests. The mean +/- SD time required to perform the individual 6MWT, ISWT and ESWT was 12.8 +/- 2.5, 14.7 +/- 3.7 and 16.3 +/- 5.0 min respectively; in comparison to CPET which was 51.2 +/- 12.7 min. Only one assessor was required to perform all field walking tests and no adverse events occurred. CONCLUSIONS: The ISWT is a promising measure of functional exercise capacity in lung cancer. Findings need to be confirmed in a larger sample prior to translation into practice. PMID- 26264472 TI - Time to abandon the use of HSMRs in the NHS. PMID- 26264473 TI - Cancer in Australia 2014: actual incidence data from 1982 to 2011 and mortality data from 1982 to 2012 with projections to 2014. AB - AIM: The Australian Institute of Health and Welfare (AIHW) is a major national agency that provides authoritative information and statistics on Australia's health and welfare. The AIHW and the Australasian Association of Cancer Registries collaborate every year to provide updated information on cancer occurrences and trends in Australia. METHOD: The actual number of cases diagnosed and deaths, for all cancers combined and selected cancers, are presented from 1982 to 2011 for incidence and from 1982 to 2012 for mortality, with projections to 2014. Data on key population groups, survival, prevalence, hospitalizations and national population screening programs are also provided. RESULTS: In 2014, it was estimated that 123 920 new cases of cancer (excluding basal and squamous cell carcinoma of the skin) were diagnosed. Prostate cancer was the most commonly diagnosed cancer in males whereas breast cancer was the most commonly diagnosed cancer in females. It was estimated that 45 780 deaths from cancer occurred in Australia in 2014. Lung cancer was the most common cause of cancer death in both males and females. CONCLUSION: From 1982 to 2014, it was estimated that the number of new cancer cases diagnosed in Australia more than doubled from 47 417 to 123 920. More males (55%) than females (45%) were diagnosed with cancer in 2014. From 1982 to 2014, the number of people who died in Australia from cancer almost doubled from 24 922 to 45 780. In 2014, more males (57%) than females (43%) were estimated to have died from cancer. PMID- 26264474 TI - Retropubic tension-free vaginal tape and inside-out transobturator tape: a long term randomized trial. AB - INTRODUCTION AND HYPOTHESIS: The tension-free vaginal tape (TVT) and inside-out transobturator tape (TVT-O) are first-line surgical treatments for stress urinary incontinence (SUI). However, there is a lack of information regarding the long term comparative safety of these procedures. METHODS: A total of 140 SUI patients were randomized to the TVT or TVT-O procedure and were interviewed by an independent investigator at the follow-up. The primary outcomes were the proportions of patients with long-term postoperative complications. The secondary outcomes included the cure rates, quality of life (QOL) and sexual function based on validated questionnaires. RESULTS: One hundred and twenty (85.71%) patients completed the long-term follow-up. More TVT patients experienced perioperative complications (P < 0.05). However, in a mean follow-up of 95 months, no significant between-group difference was found in the proportions of patients with long-term complications or in the variety of reported complications. The long-term complication rates for TVT and TVT-O were 43.1% and 27.4% respectively (P = 0.07). De novo voiding (15.8%) and storage symptoms (10.8%) were the primary long-term complications. Tape exposure was possible up to 7 years after TVT-O. The objective cure rates of TVT and TVT-O procedures were 79.30 and 69.35% respectively, which were not significantly higher than the subjective rates. The Pelvic Floor Impact Questionnaire (PFIQ-7) scores remained improved (P < 0.001) after both procedures, even at the 95-month follow-up. No difference was observed in the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire Short Form (PISQ-12) scores after either procedure. CONCLUSIONS: In the long term, the proportion of patients with complications and the cure rates of the two procedures did not differ significantly. The long-term complication rates were high, but morbidity was low, and the QOL remained improved. PMID- 26264475 TI - Preoperative vaginal estrogen and midurethral sling exposure: a retrospective cohort study. AB - INTRODUCTION AND HYPOTHESIS: We evaluated whether the use of estrogen vaginally prior to synthetic midurethral sling insertion mediates the risk of mesh exposure. A secondary aim was to evaluate other factors that may be associated with mesh exposure. METHODS: We performed a retrospective cohort study of patients undergoing midurethral sling insertion from January to December 2010 within the Southern California Permanente Medical Group. Women who used estrogen vaginally prior to surgery were classified as those who filled a prescription between 1 and 45 days before surgery or whose medical records indicated its use at the time of preoperative evaluation. Logistic regression analysis was used to calculate odds ratios (OR) and 95 % confidence intervals (CI) for factors associated with mesh exposure while controlling for confounding variables. RESULTS: A total of 1544 patients met inclusion criteria, of whom 248 (16.1 %) used estrogen vaginally prior to surgery. Mean age was 53.7 years (range 27-89). Thirty-seven (2.4 %) women were diagnosed with mesh exposure, of whom 19 underwent surgical reoperation. In multivariate logistic regression analysis, preoperative use of estrogen vaginally was not associated with the risk of mesh exposure (OR 0.79, CI 0.26-2.38, p = 0.67). Age, body mass index, menopausal status, use of hormone replacement therapy, smoking status, and diabetes were not associated with risk of mesh exposure. CONCLUSIONS: Preoperative use of estrogen vaginally did not appear to mediate the risk of mesh exposure following midurethral sling placement in this cohort. PMID- 26264476 TI - Digitation associated with defecation: what does it mean in urogynaecological patients? AB - INTRODUCTION AND HYPOTHESIS: Obstructed defecation is a common symptom complex in urogynaecological patients, and perineal, vaginal and/or anal digitation may required for defecation. Translabial ultrasound can be used to assess anorectal anatomy, similar to defecation proctography. The aim of the present study was to determine the association between different forms of digitation (vaginal, perineal and anal) and abnormal posterior compartment anatomy. METHODS: A total of 271 patients were analysed in a retrospective study utilising archived ultrasound volume datasets. Symptoms of obstructed defecation (straining at stool, incomplete bowel emptying, perineal, vaginal and anal digitation) were ascertained on interview. Postprocessing of stored 3D/4D translabial ultrasound datasets obtained on maximal Valsalva was used to diagnose descent of the rectal ampulla, rectocoele, enterocoele and rectal intussusception at a later date, blinded to all clinical data. RESULTS: Digitation was reported by 39 % of our population. The position of the rectal ampulla on Valsalva was associated with perineal (p = 0.02) and vaginal (p = 0.02) digitation. The presence of a true rectocoele was significantly associated with perineal (p = 0.04) and anal (p = 0.03) digitation. Rectocoele depth was associated with all three forms of digitation (P = 0.005-0.02). The bother of symptoms of obstructed defecation was strongly associated with digitation (all P < = 0.001), with no appreciable difference in bother among the three forms. CONCLUSION: Digitation is common, and all forms of digitation are associated with abnormal posterior compartment anatomy. It may not be necessary to distinguish between different forms of digitation in clinical practice. PMID- 26264477 TI - Reduction in keratin aggregates in epidermolysis bullosa simplex keratinocytes after pretreatment with trimethylamine N-oxide. PMID- 26264479 TI - Protective effects of (-)-epigallocatechin-3-gallate against acetaminophen induced liver injury in rats). AB - (-)-Epigallocatechin-3-gallate (EGCG) is the most abundant catechin with various biological activities found in tea. In this study, the effects of EGCG on the metabolism and toxicity of acetaminophen in rat liver were investigated. Male Sprague-Dawley rats were fed a controlled diet without or with EGCG (0.54 %, w/w) for 1 week and were then intraperitoneally injected with acetaminophen (1 g/kg body weight) and killed after 12 h. Concentrations of acetaminophen and its conjugates in plasma and liver were then determined. The cytochrome P450 (CYP) and phase II enzymes activities were also evaluated. Rats fed the EGCG diet had lower plasma alanine aminotransferase and aspartate aminotransferase activities, as indices of hepatotoxicity, after acetaminophen treatment. Morphological damage by acetaminophen was lower in rats fed the EGCG diet. In addition, EGCG significantly reduced hepatic activities of midazolam 1-hydroxylation (CYP3A), nitrophenol 6-hydroxylase (CYP2E1), UDP-glucurosyltransferase, and sulfotransferase. Finally, EGCG feeding reduced acetaminophen-glucuronate and acetaminophen-glutathione contents in plasma and liver. These results indicate that EGCG feeding may reduce the metabolism and toxicity of acetaminophen in rats. PMID- 26264480 TI - The Malnutrition Universal Screening Tool (MUST) and a nutrition education program for high risk cancer patients: strategies to improve dietary intake in cancer patients. AB - Four hundred and forty-four high-risk oncology patients with malnutrition participated in this study aimed at assessing the effectiveness of nutrition education on improving an oncology patient's dietary intake. We used a nutritional risk screening to select oncology patients in need of nutritional care. Team Nutrition provides technical assistance for foodservice, nutrition education for patients and their caregivers, and support for healthy eating and physical activity to improve their diets and their lives. The average contribution of protein and total energy of each patient increased after imparting the nutritional education to them. Thus, nutritional education is an effective measure to bring about a favorable and significant change in oncology patients' nutrient intake. PMID- 26264478 TI - Molecular dynamics simulation of water permeation through the alpha-hemolysin channel. AB - The alpha-hemolysin (AHL) nanochannel is a non-selective channel that allows for uncontrolled transport of small molecules across membranes leading to cell death. Although it is a bacterial toxin, it has promising applications, ranging from drug delivery systems to nano-sensing devices. This study focuses on the transport of water molecules through an AHL nanochannel using molecular dynamics (MD) simulations. Our results show that AHL can quickly transport water across membranes. The first-passage time approach was used to estimate the diffusion coefficient and the mean exit time. To study the energetics of transport, the potential of mean force (PMF) of a water molecule along the AHL nanochannel was calculated. The results show that the energy barriers of water permeation across a nanopore are always positive along the channel and the values are close to thermal energy (kBT). These findings suggest that the observed quick permeation of water is due to small energy barriers and a hydrophobic inner channel surface resulting in smaller friction. We speculate that these physical mechanisms are important in how AHL causes cell death. PMID- 26264481 TI - The P-wave morphology: what does it tell us? AB - P-wave morphology and duration reveals several aspects of the atria: Proper function, fibrosis, dyssynchrony, and activation paths can be inferred from the surface P-wave analysis. Surface electrocardiogram (ECG) can help differentiating enlargements of the atria from conduction defects including intra- and interatrial block.The purpose of this paper is to review normal atrial morphology and the most relevant abnormal patterns. PMID- 26264482 TI - Bradycardia: sinus and AV node dysfunction. AB - The surface electrocardiogram (ECG) holds many clues with regard to the etiology of bradycardia and site of atrioventricular (AV) block. Bedside maneuvers may prove helpful in cases of 2:1 AV block or situations where the data is not all concordant. Wenckebach conduction may occur in any region of the heart, and there are nonpathologic mimickers of Mobitz II AV block as well. The surface ECG may aid in the inference of etiology for better than expected or slowed rather than blocked AV conduction. Sinus node dysfunction may present in several forms and often accompanies other conduction system disease. On occasion invasive studies may be required to help elucidate the mechanism of bradycardia. PMID- 26264483 TI - [Mapping and ablation of a mechanically blocked concealed accessory pathway under repeated adenosine bolus infusions]. AB - During mapping and catheter ablation of an accessory pathway, a mechanically induced conduction block can occur. Adenosine is used to detect dormant conduction of incomplete ablation lesions. Presented in this article is the case of a patient with a left-sided accessory pathway, which was mechanically blocked during the mapping procedure and could only be successfully ablated after repeated adenosine bolus infusions, which resulted in intermittent restitution of conduction via the accessory pathway. PMID- 26264484 TI - Erratum. PMID- 26264490 TI - Novel binders derived from an albumin-binding domain scaffold targeting human prostate secretory protein 94 (PSP94). PMID- 26264491 TI - High doses of Baclofen as suicide attempt in patients with alcohol use disorders A serious concern. AB - Baclofen is increasingly being used as an off label anti-craving agent in alcohol use disorders in various parts of the world. The lack of proper recommendations regarding the dosage has important implications for safety in clinical management. In this context, we report two patients who were started with Baclofen as an anti-craving agent, and later developed serious complications following acute self inflicted overdose. We also highlight the important mechanisms of such complications and precautions that needs to be exerted while prescribing. PMID- 26264492 TI - Biomarkers to enhance accuracy and precision of prediction of short-term and long term outcome after spontaneous intracerebral haemorrhage: a study protocol for a prospective cohort study. AB - BACKGROUND: Several studies reported prognostic value of biomarker in intracerebral hemorrhagic (ICH) but they are either preliminary observation or inadequately powered to analyse independent contribution of biomarkers over and above clinical and neuroimaging data. OBJECTIVE: To examine whether the biomarker can significantly add to the predictive accuracy of prognosis of ICH. METHOD/DESIGN: In a multi-centric prospective cohort study, 1020 patients with ICH within 72 hours of onset are being recruited. After obtaining written informed consent from patients/proxy, venous blood sample (10 ml) is being collected and analysed for C-reactive protein (CRP) level, S100B, Glial fibrillary acidic protein (GFAP), Troponin, change in leukocyte count and Copeptin levels. The patients are telephonically followed using stroke scales (Barthel Index and modified Rankin Scale) at 3, 6, 12 months and 2 years after the recruitment. DISCUSSION: This protocol will aim at predicting the short term or long term prognosis with the use of clinical, neuroimaging and biomarkers in order to help clinician to stratify patients for early referral or intervention. PMID- 26264494 TI - Time-Resolved Detection and Analysis of Single Nanoparticle Electrocatalytic Impacts. AB - There is considerable interest in understanding the interaction and activity of single entities, such as (electro)catalytic nanoparticles (NPs), with (electrode) surfaces. Through the use of a high bandwidth, high signal/noise measurement system, NP impacts on an electrode surface are detected and analyzed in unprecedented detail, revealing considerable new mechanistic information on the process. Taking the electrocatalytic oxidation of H2O2 at ruthenium oxide (RuOx) NPs as an example, the rise time of current-time transients for NP impacts is consistent with a hydrodynamic trapping model for the arrival of a NP with a distance-dependent NP diffusion-coefficient. NP release from the electrode appears to be aided by propulsion from the electrocatalytic reaction at the NP. High-frequency NP impacts, orders of magnitude larger than can be accounted for by a single pass diffusive flux of NPs, are observed that indicate the repetitive trapping and release of an individual NP that has not been previously recognized. The experiments and models described could readily be applied to other systems and serve as a powerful platform for detailed analysis of NP impacts. PMID- 26264493 TI - Elevated levels of factor VIII and subsequent risk of all-cause mortality: results from the MEGA follow-up study. AB - BACKGROUND: Factor VIII (FVIII) levels are increased in individuals with a non-O blood group and play a role in the etiology of thrombosis. High FVIII levels have also been associated with increased all-cause mortality. OBJECTIVE: We explored whether elevated FVIII levels are associated with an increased risk of death in patients who had venous thrombosis and in individuals from the general population, and to what extent this association is causal. METHODS: We followed 2178 patients with previous venous thrombosis and 2827 age and sex-matched community controls for on average 5.5 years and measured their FVIII levels and ABO blood group. RESULTS: All-cause mortality increased in a dose-response fashion with increasing percentiles of FVIII levels. In the thrombosis patients the risk was highest above the 97.5th percentile (FVIII > 199 IU dL(-1) ) with an adjusted hazard ratio (HR) of 3.1 (95% confidence interval [CI], 0.9-10.8) as compared with patients in the 25th percentile category (FVIII <= 85 IU dL(-1) ). The adjusted HR was 4.5 (95% CI, 1.4-14.3) in controls. Using non-O blood group as a measure of genetically elevated FVIII levels to determine a causal relationship between FVIII and death showed observed HRs of 0.99 (95% CI, 0.72 1.36) in patients and 1.25 (95% CI, 0.82-1.90) in controls. CONCLUSIONS: We showed a dose-response relationship between high FVIII levels and risk of death in venous thrombosis patients and in individuals from the general population. However, environmental factors, such as chronic comorbidities and chronic inflammation, are at least in part responsible for the association between factor VIII and mortality. PMID- 26264495 TI - Galectin 3 as a guardian of the tumor microenvironment. AB - Galectin 3 is a member of a family of beta-galactoside binding proteins and has emerged as an important regulator of diverse functions critical in cancer biology including apoptosis, metastasis, immune surveillance, molecular trafficking, mRNA splicing, gene expression, and inflammation. Galectin 3's ability to support cancer cell survival by intra-cellular and extra-cellular mechanisms suggests this molecule is an important component of the tumor microenvironment that potentially could be targeted for therapy. Data is emerging that Galectin 3 is elevated in many cancers including solid tumors and the cancers of the blood. Galectin 3 also appears to be a key molecule produced by tumor microenvironment support cells including mesenchymal stromal cells (MSC) to suppress immune surveillance by killing T cells and interfering with NK cell function and by supporting metastasis. Levels of Galectin 3 increase in the MSC of aging mice and perhaps this contributes to the development of cancer in the elderly. Galectin 3 modulates surface protein expression of a diverse set of glycoproteins including CD44 by regulating endocytosis of these proteins. In addition, Galectin 3 binding to receptor kinases such as CD45 and the T cell receptor is critical in the regulation of their function. In this review I will examine the various mechanisms how Galectin 3 supports chemoresistance and metastasis in solid tumors and in leukemia and lymphoma. I will also discuss possible therapeutic strategies to target this Galectin for cancer therapy. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza. PMID- 26264496 TI - Effect of neck cut position on time to collapse in halal slaughtered cattle without stunning. AB - This study examined the effect of neck cut position on the time to physical collapse in upright restrained halal slaughtered cattle (n = 644). Time to collapse was used as an indirect indicator of the early stages of onset of unconsciousness. Cattle were slaughtered with either a conventional low (LNC) (n=561) or a high neck cut (HNC) (n = 83). Mean time to final collapse was higher in the LNC compared to HNC group (18.9 +/- 1.1s and 13.5 +/- 1.3s respectively (P < 0.01)). The mean false aneurysm scores were higher in the LNC cattle (0.8 +/- 0.0) compared to the HNC (0.6 +/- 0.1) (P < 0.01). Animals that took > 20s to final collapse had larger false aneurysms. In summary, the HNC reduced the mean time to final collapse and the frequency of animals that took longer than 20s to collapse. PMID- 26264498 TI - A morphoelastic model for dermal wound closure. AB - We develop a model of wound healing in the framework of finite elasticity, focussing our attention on the processes of growth and contraction in the dermal layer of the skin. The dermal tissue is treated as a hyperelastic cylinder that surrounds the wound and is subject to symmetric deformations. By considering the initial recoil that is observed upon the application of a circular wound, we estimate the degree of residual tension in the skin and build an evolution law for mechanosensitive growth of the dermal tissue. Contraction of the wound is governed by a phenomenological law in which radial pressure is prescribed at the wound edge. The model reproduces three main phases of the healing process. Initially, the wound recoils due to residual stress in the surrounding tissue; the wound then heals as a result of contraction and growth; and finally, healing slows as contraction and growth decrease. Over a longer time period, the surrounding tissue remodels, returning to the residually stressed state. We identify the steady state growth profile associated with this remodelled state. The model is then used to predict the outcome of rewounding experiments designed to quantify the amount of stress in the tissue, and also to simulate the application of pressure treatments. PMID- 26264497 TI - Tumor-associated macrophages in cancers. AB - Tumor-associated macrophages (TAMs) are major component of leukocytic infiltrate of tumors and play important roles in progression and regression of tumors. Tumor microenvironment determines the mutual conversion between M1 and M2 macrophages. In many kinds of tumors, M2 type macrophages are of the majority in TAMs and promote tumor progression and metastasis. The dynamic balance and interaction between TAMs and tumor cells have important effects on the occurrence and development of tumor. TAMs in malignant tumors are useful for clinical diagnosis and may provide a novel target for cancer treatment. PMID- 26264499 TI - Effect of knee position on the ultrasound elastography appearance of the patellar tendon. PMID- 26264500 TI - Synthesis and biological evaluation of new symmetric curcumin derivatives. AB - A series of novel curcumin bisacetamides aiming of enriching their biological activities have been synthesized. The synthesized compounds were screened for their in vitro antioxidant, anti-inflammatory and cytotoxic activities. All the compounds exhibited potent to good anti-inflammatory, antioxidant and noteworthy cytotoxic activities. PMID- 26264501 TI - Factors influencing the cytotoxicity of alpha-methylene-gamma-hydroxy esters against pancreatic cancer. AB - A systematic study to identify the factors influencing the cytotoxicity of alpha methylene-gamma-hydroxy esters against three pancreatic cancer cell lines (Panc 1, MIA-PaCa-2, and BxPC-3) has established that, in addition to Michael acceptor abilities, the possibility to lactonize to alpha-methylene-gamma-butyrolactones is as important. The substitution pattern and the number of carbons between the hydroxy and ester moieties also influence the bio-activity. PMID- 26264502 TI - Biological evaluation of angular disubstituted naphthoimidazoles as anti inflammatory agents. AB - A series of naphthoimidazoles derivatives (3a-3f) were tested for potential anti inflammatory activity on lipopolysaccharide (LPS)-treated macrophages. Naphthoimidazole 3e exhibited significant inhibitory effects on nitric oxide (NO) production (IC50 <10MUM) and decreased the expression of nitric oxide synthase-2 (NOS-2) and cycloxygenase-2 (COX-2) enzymes. It also inhibited the activation of transcription factor NF-kappaB. Naphthoimidazole 3e might represent a starting point for the synthesis of new anti-inflammatory naphthoimidazoles derivatives. PMID- 26264503 TI - Discovery of 1-hydroxypyridine-2-thiones as selective histone deacetylase inhibitors and their potential application for treating leukemia. AB - Histone deacetylase (HDAC) is a validated target for pursuing anticancer agents. However, obtaining a selective inhibitor against a given HDAC member remains a significant challenge. We report here the use of 1-hydroxypyridine-2-thione (1HPT) as a key pharmacophore for zinc-binding can result in highly selective HDAC inhibitors. 1HPT-6-carboxylic acid exhibits selective inhibition of HDAC6 with an IC50 of 150 nM that corresponds to a remarkable 0.9 ligand efficiency. Two analogs with simple amino acids shows nearly 600-fold selectivity among the eleven zinc-dependent HDACs. At low micromolar concentration these compounds inhibit the growth of HDAC8-overexpressing chronic myelogenous leukemia cells and specific form of acute myelogenous leukemia cells. Their potential mode of binding was examined by molecular docking and their stability was assessed in mouse and human plasma. Together the results suggest 1HPT analogs exhibit promising therapeutic potential for further development as anticancer agents to treat leukemia. PMID- 26264504 TI - Trauma versus no trauma: an analysis of the effect of tear mechanism on tendon healing in 1300 consecutive patients after arthroscopic rotator cuff repair. AB - BACKGROUND: Patients with rotator cuff tears often recall a specific initiating event (traumatic), whereas many cannot (nontraumatic). It is unclear how important a history of trauma is to the outcomes of rotator cuff repair. METHODS: This question was addressed in a study cohort of 1300 consecutive patients who completed a preoperative questionnaire regarding their shoulder injury and had a systematic evaluation of shoulder range of motion and strength, a primary arthroscopic rotator cuff repair performed by a single surgeon, an ultrasound scan, and the same subjective and objective measurements made of their shoulder 6 months after surgery. Post hoc, this cohort was separated into 2 groups: those who reported no history of trauma on presentation (n = 489) and those with a history of traumatic injury (n = 811). RESULTS: The retear rate in the group with no history of trauma was 12%, whereas that of the group with a history of trauma was 14% (P = .36). Those patients with a history of shoulder trauma who waited longer than 24 months had higher retear rates (20%) than those who had their surgery earlier (13%) (P = .040). CONCLUSION: Recollection of a traumatic initiating event had little effect on the outcome of arthroscopic rotator cuff repair. Duration of symptoms was important in predicting retears if patients recalled a specific initiating event but not in patients who did not recall any specific initiating event. Patients with a history of trauma should be encouraged to have their rotator cuff tear repaired within 2 years. PMID- 26264505 TI - Peripartum changes in partnership quality among women with and without anxiety and depressive disorders prior to pregnancy: a prospective-longitudinal study. AB - The purpose of this study is to prospectively examine peripartum changes in partnership characteristics among women with and without anxiety and depressive disorders prior to pregnancy. In the prospective-longitudinal Maternal Anxiety in Relation to Infant Development (MARI) study, n = 306 expectant mothers completed up to seven waves of assessment from early pregnancy until 16 months postpartum. Lifetime anxiety and depressive disorders according to the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) were evaluated at baseline using the Composite International Diagnostic Interview for Women (CIDI V, Martini et al. 2009). Partnership characteristics were assessed during pregnancy as well as 4 and 16 months postpartum using the Partnership Questionnaire (Hahlweg 1996). Linear regressions were applied to test associations between diagnostic status prior to pregnancy and peripartum partnership characteristics. Compared to women without anxiety and depressive disorders prior to pregnancy, women with comorbid anxiety and depressive disorders reported less tenderness during pregnancy, less postpartum tenderness, satisfaction, and overall partnership quality as well as a lower decrease in communication from pre- to postpartum. Women with pure depressive disorders and comorbid anxiety and depressive disorders prior to pregnancy indicated a higher increase in quarreling from pre- to postpartum. Findings suggest that women with depressive (and comorbid anxiety) disorders prior to pregnancy are at elevated risk for an unfavorable peripartum partnership development and might thus profit from targeted family interventions during this period. PMID- 26264506 TI - Women's experiences of symptoms of posttraumatic stress disorder (PTSD) after traumatic childbirth: a review and critical appraisal. AB - This paper critically analyses nine studies on postnatal posttraumatic stress disorder (PTSD) following traumatic childbirth, in order to find common themes of PTSD symptoms, using the cognitive model of PTSD as a guide; it critically appraised one of the studies in depth and it attempted to explain the lived experience of women suffering from postnatal PTSD following traumatic childbirth and the suitability of cognitive behavioural therapy (CBT) for postnatal PTSD. This paper found that women following traumatic childbirth do experience postnatal PTSD; postnatal PTSD symptoms are similar to PTSD symptoms of other events and that CBT for PTSD of other events is just as effective for postnatal PTSD. Future recommendations include more qualitative studies with interpretative phenomenological approach in order to establish evidence-based CBT treatment for this client group, and more referrals need to be sent to the psychological services for CBT intervention. PMID- 26264507 TI - Fumed Silica-Based Single-Ion Nanocomposite Electrolyte for Lithium Batteries. AB - A composite lithium electrolyte composed of polyelectrolyte-grafted nanoparticles and polyethylene glycol dimethyl ether (PEGDME) is synthesized and characterized. Polyanions immobilized by the silica nanoparticles have reduced anion mobility. Composite nanoparticles grafted by poly(lithium 4-styrenesulfonate) only have moderate conductivity at 60 degrees C. Almost an order increase of the conductivity to ~10(-6) S/cm is achieved by co-polymerization of the poly(ethylene oxide) methacrylate with sodium 4-styrenesulfonate, which enhances dissociation between lithium cation and polyanion and facilitates lithium ion transfer from the inner part of the polyelectrolyte layer. This composite electrolyte has the potential to suppress lithium dendrite growth and enable the use of lithium metal anode in rechargeable batteries. PMID- 26264509 TI - Nanomechanics of RDX Single Crystals by Force-Displacement Measurements and Molecular Dynamics Simulations. AB - Nanoenergetic material modifications for enhanced performance and stability require an understanding of the mechanical properties and molecular structure property relationships of materials. We investigate the mechanical and tribological properties of single-crystal hexahydro-1,3,5-trinitro-s-triazine (RDX) by force-displacement microscopy and molecular dynamics (MD). Our MD simulations reveal the RDX reduced modulus (Er) depends on the particular crystallographic surface. The predicted Er values for the respective (210) and (001) surfaces are 26.8 and 21.0 GPa. Further, our simulations reveal a symmetric and fairly localized deformation occurring on the (001) surface compared to an asymmetric deformation on the (210) surface. The predicted hardness (H) values are nearly equal for both surfaces. The predicted Er and H values are ~33% and 17% greater than the respective experimental values of 0.798 +/- 0.030 GPa and 22.9 +/- 0.7 GPa for the (210) surface and even larger than those reported previously. Our experimental H and Er values are ~19% and 9% greater than those reported previously for the (210) surface. The difference between the experimental values reported here and elsewhere stems in part from an inaccurate determination of the contact area. We employ the parameter ?H/Er, which is independent of area, as a means to compare present and past results, and find excellent agreement, within a few percent, between our predicted and experimental results and between our results and those obtained from previous nanoindentation experiments. Also, we performed nanoscratch simulations of the (210) and (001) surfaces and nanoscratch tests on the (210) surface and present values of the dynamic coefficient of deformation friction. PMID- 26264508 TI - Angiotensin-(1-7) counteracts the effects of Ang II on vascular smooth muscle cells, vascular remodeling and hemorrhagic stroke: Role of the NFkB inflammatory pathway. AB - Angiotensin (Ang)-(1-7) is a potential vasoprotective peptide. In the present study, we investigated its counteractive effects to Ang II on vascular smooth muscle cells (VSMCs) and intracerebral hemorrhagic stroke (ICH) through inflammatory mechanism. In in vitro experiments, human brain VSMCs (HBVSMCs) were treated with vehicle, Ang II, Ang II+Ang-(1-7), Ang II+A-779 or Ang II+Ang-(1 7)+A-779 (Mas receptor antagonist). HBVSMC proliferation, migration and apoptosis were determined by methyl thiazolyltetrazolium, wound healing assay and flow cytometry, respectively. In in vivo experiments, C57BL/6 mice were divided into vehicle, Ang II, Ang II+Ang-(1-7), Ang II+A-779 or Ang II+Ang-(1-7)+A-779 groups before they were subjected to collagenase-induced ICH or sham surgery. Hemorrhage volume and middle cerebral artery (MCA) remodeling were determined by histological analyses. Levels of NFkappaB, inhibitor of kappaBalpha (IkappaBalpha), tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein 1 (MCP-1) and interleukin (IL-8) were measured by western blot or ELISA. We found that 1) Ang II increased HBVSMC migration, proliferation and apoptosis, and increased the blood pressure (BP), neurological deficit score, MCA remodeling and hemorrhage volume in ICH mice. 2) Ang-(1-7) counteracted these effects of Ang II, which was independent of BP, with the down-regulation of NFkappaB, up regulation of IkappaBalpha, and decreased levels of TNF-alpha, MCP-1 and IL-8. 3) The beneficial effects of Ang-(1-7) could be abolished by A-779. In conclusion, Ang-(1-7) counteracts the effects of Ang II on ICH via modulating NFkappaB inflammation pathway in HBVSMCs and cerebral microvessels. PMID- 26264510 TI - Elucidation of Molecular Mechanisms Behind the Self-Assembly Behavior of Chitosan Amphiphilic Derivatives Through Experiment and Molecular Modeling. AB - PURPOSE: Chitosan-based polymeric micelles (CBPMs) are considered as promising carriers for delivery of anticancer drugs, imaging agents and genes. To optimize the physicochemical, pharmaceutical and biological properties of CBPMs, the molecular mechanisms behind the self-assembly behavior of chitosan (CHI) amphiphilic derivatives are elucidated. METHODS: This study has two stages. In the experimental stage, dexamethasone (DEX) as a hydrophobic group is grafted to CHI in three degrees of substitution in order to obtain CHI derivatives with different degrees of hydrophobicity. These new CHI amphiphilic derivatives (CHI_DEXs) form micelles in water where their critical aggregation concentration (CAC), size and zeta potential are measured. Through comparing the results of these measurements, the change of self-assembly behavior of CHI_DEXs in response to increasing their hydrophobicity is evaluated. Correlating this evaluation with the results of the 13 MD simulations conducted on CHI_DEXs in atomistic molecular dynamics (MD) simulation stage, reveals the molecular mechanisms behind the self assembly behavior of CHI_DEXs. RESULTS: Our evaluation of the experimental results reveals that increasing hydrophobicity of a CHI amphiphilic derivative would not necessarily cause it to form micelles with lower CAC value, smaller size and lower zeta potential. The MD simulations reveal that there exists a balance between intra- and inter-chain interactions which is responsible for the self-assembly behavior of CHI amphiphilic derivatives. CONCLUSION: An increase in DS of the hydrophobic group triggers a cascade of molecular events that shifts the balance between intra- and inter-chain interactions leading to changes in the CAC, size and zeta potential of the CBPMs. PMID- 26264511 TI - Development of a Sustained Release Solid Dispersion Using Swellable Polymer by Melting Method. AB - PURPOSE: This study is to design a sustained release solid dispersion using swellable polymer by melting method. METHODS: Polyethylene glycol 6000 (PEG 6000) and hydroxypropyl methylcellulose 4000 (HPMC 4000) were used in solid dispersion for not only enhancing drug dissolution rate but also sustaining drug release. HPMC 4000 is a common swellable polymer in matrix sustained release dosage form, but could not be used in preparation of solid dispersion by melting method. However, the current study utilized the swelling capability of HPMC 4000 accompanied by the common carrier PEG 6000 in solid dispersion to accomplish the goal. RESULTS: While PEG 6000 acted as a releasing stimulant carrier and provided an environment to facilitate the swelling of HPMC 4000, this swellable polymer could act as a rate-controlling agent. This greatly assisted the dissolution enhancement by changing the crystalline structure of drug to more amorphous form and creating a molecular interaction. CONCLUSIONS: These results suggested that this useful technique can be applied in designing a sustained release solid dispersion with many advantages. PMID- 26264512 TI - Development of Disposal Systems for Deactivation of Unused/Residual/Expired Medications. AB - PURPOSE: The objective of this work was to identify deactivation agents and develop a disposal system for unused/ residual/ expired medications. METHODS: Deactivation agents screened included oxidizing agent-sodium percarbonate, hydrolysis agent- sodium carbonate and adsorbants- zeolite and activated carbon. Deactivation studies using these agents were performed on four active pharmaceutical agents (APIs) including ketoprofen, dexamethasone sodium phosphate, metformin hydrochloride and amoxicillin trihydrate. Disposal systems were also designed for deactivation studies on dexamethasone pills, amoxicillin trihydrate capsules and fentanyl transdermal patches (Duragesic(r)). Briefly, APIs/ dosage forms were allowed to be in close contact with deactivation agents for a specified period of time and percentage decrease in the amount of API from the initial amount was measured. RESULTS: Sodium percarbonate and sodium carbonate were only successful in deactivation of amoxicillin trihydrate API. Adsorption agents resulted in more universal deactivation with activated carbon resulting in efficient deactivation of most APIs and all dosage forms tested. Also adsorption of oral dosage medications on activated carbons was maintained even on dilution and shaking and no desorption was observed. CONCLUSIONS: Deactivation systems containing activated carbon are promising for efficient, safe and environment friendly disposal of unused/residual/expired medications. PMID- 26264513 TI - Allogeneic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy. AB - Haematopoietic stem cell transplantation has been proposed as treatment for mitochondrial neurogastrointestinal encephalomyopathy, a rare fatal autosomal recessive disease due to TYMP mutations that result in thymidine phosphorylase deficiency. We conducted a retrospective analysis of all known patients suffering from mitochondrial neurogastrointestinal encephalomyopathy who underwent allogeneic haematopoietic stem cell transplantation between 2005 and 2011. Twenty four patients, 11 males and 13 females, median age 25 years (range 10-41 years) treated with haematopoietic stem cell transplantation from related (n = 9) or unrelated donors (n = 15) in 15 institutions worldwide were analysed for outcome and its associated factors. Overall, 9 of 24 patients (37.5%) were alive at last follow-up with a median follow-up of these surviving patients of 1430 days. Deaths were attributed to transplant in nine (including two after a second transplant due to graft failure), and to mitochondrial neurogastrointestinal encephalomyopathy in six patients. Thymidine phosphorylase activity rose from undetectable to normal levels (median 697 nmol/h/mg protein, range 262-1285) in all survivors. Seven patients (29%) who were engrafted and living more than 2 years after transplantation, showed improvement of body mass index, gastrointestinal manifestations, and peripheral neuropathy. Univariate statistical analysis demonstrated that survival was associated with two defined pre-transplant characteristics: human leukocyte antigen match (10/10 versus <10/10) and disease characteristics (liver disease, history of gastrointestinal pseudo-obstruction or both). Allogeneic haematopoietic stem cell transplantation can restore thymidine phosphorylase enzyme function in patients with mitochondrial neurogastrointestinal encephalomyopathy and improve clinical manifestations of mitochondrial neurogastrointestinal encephalomyopathy in the long term. Allogeneic haematopoietic stem cell transplantation should be considered for selected patients with an optimal donor. PMID- 26264514 TI - Network localization of neurological symptoms from focal brain lesions. AB - A traditional and widely used approach for linking neurological symptoms to specific brain regions involves identifying overlap in lesion location across patients with similar symptoms, termed lesion mapping. This approach is powerful and broadly applicable, but has limitations when symptoms do not localize to a single region or stem from dysfunction in regions connected to the lesion site rather than the site itself. A newer approach sensitive to such network effects involves functional neuroimaging of patients, but this requires specialized brain scans beyond routine clinical data, making it less versatile and difficult to apply when symptoms are rare or transient. In this article we show that the traditional approach to lesion mapping can be expanded to incorporate network effects into symptom localization without the need for specialized neuroimaging of patients. Our approach involves three steps: (i) transferring the three dimensional volume of a brain lesion onto a reference brain; (ii) assessing the intrinsic functional connectivity of the lesion volume with the rest of the brain using normative connectome data; and (iii) overlapping lesion-associated networks to identify regions common to a clinical syndrome. We first tested our approach in peduncular hallucinosis, a syndrome of visual hallucinations following subcortical lesions long hypothesized to be due to network effects on extrastriate visual cortex. While the lesions themselves were heterogeneously distributed with little overlap in lesion location, 22 of 23 lesions were negatively correlated with extrastriate visual cortex. This network overlap was specific compared to other subcortical lesions (P < 10(-5)) and relative to other cortical regions (P < 0.01). Next, we tested for generalizability of our technique by applying it to three additional lesion syndromes: central post stroke pain, auditory hallucinosis, and subcortical aphasia. In each syndrome, heterogeneous lesions that themselves had little overlap showed significant network overlap in cortical areas previously implicated in symptom expression (P < 10(-4)). These results suggest that (i) heterogeneous lesions producing similar symptoms share functional connectivity to specific brain regions involved in symptom expression; and (ii) publically available human connectome data can be used to incorporate these network effects into traditional lesion mapping approaches. Because the current technique requires no specialized imaging of patients it may prove a versatile and broadly applicable approach for localizing neurological symptoms in the setting of brain lesions. PMID- 26264517 TI - Asymmetrical diacylglycerol dynamics on the cytosolic and lumenal sides of a single endomembrane in living cells. AB - The elucidation of lipid dynamics on the cytosolic and lumenal sides of a single endomembrane has been challenging in living cells because of the lack of appropriate methods. Diacylglycerol (DAG) is a lipid second messenger that is produced by enzymes that reside on both the cytosolic and lumenal sides of the endomembrane. In the present study, we attempted to observe both the cytosolic and lumenal DAG dynamics at endomembranes including the Golgi apparatus and the endoplasmic reticulum in Madin-Darby canine kidney (MDCK) cells. We developed a Forster resonance energy transfer (FRET)-based probe to detect DAG at the luminal side (lumenal DAG) of endomembranes. In combination with the FRET-based cytosolic DAG probe that has already been established, it was found that lumenal DAG is generated in a calcium-dependent manner by thapsigargin, which increases cytosolic calcium concentrations. In contrast, DAG production at the cytosolic side of endomembranes did not occur under the same experimental conditions. The thapsigargin-induced DAG generation was abolished by treatment with an inhibitor of sphingomyelin synthase (SMS) and phosphatidylcholine-specific phospholipase C (PC-PLC), which produce lumenal DAG. Thus, we have established a successful method for monitoring both cytosolic and lumenal DAG dynamics at the endomembrane in living cells. PMID- 26264515 TI - Structural imaging biomarkers of sudden unexpected death in epilepsy. AB - Sudden unexpected death in epilepsy is a major cause of premature death in people with epilepsy. We aimed to assess whether structural changes potentially attributable to sudden death pathogenesis were present on magnetic resonance imaging in people who subsequently died of sudden unexpected death in epilepsy. In a retrospective, voxel-based analysis of T1 volume scans, we compared grey matter volumes in 12 cases of sudden unexpected death in epilepsy (two definite, 10 probable; eight males), acquired 2 years [median, interquartile range (IQR) 2.8] before death [median (IQR) age at scanning 33.5 (22) years], with 34 people at high risk [age 30.5 (12); 19 males], 19 at low risk [age 30 (7.5); 12 males] of sudden death, and 15 healthy controls [age 37 (16); seven males]. At-risk subjects were defined based on risk factors of sudden unexpected death in epilepsy identified in a recent combined risk factor analysis. We identified increased grey matter volume in the right anterior hippocampus/amygdala and parahippocampus in sudden death cases and people at high risk, when compared to those at low risk and controls. Compared to controls, posterior thalamic grey matter volume, an area mediating oxygen regulation, was reduced in cases of sudden unexpected death in epilepsy and subjects at high risk. The extent of reduction correlated with disease duration in all subjects with epilepsy. Increased amygdalo-hippocampal grey matter volume with right-sided changes is consistent with histo-pathological findings reported in sudden infant death syndrome. We speculate that the right-sided predominance reflects asymmetric central influences on autonomic outflow, contributing to cardiac arrhythmia. Pulvinar damage may impair hypoxia regulation. The imaging findings in sudden unexpected death in epilepsy and people at high risk may be useful as a biomarker for risk-stratification in future studies. PMID- 26264518 TI - Car Gestures - Advisory warning using additional steering wheel angles. AB - Advisory warning systems (AWS) notify the driver about upcoming hazards. This is in contrast to the majority of currently deployed advanced driver assistance systems (ADAS) that manage emergency situations. The target of this study is to investigate the effectiveness, acceptance, and controllability of a specific kind of AWS that uses the haptic information channel for warning the driver. This could be beneficial, as alternatives for using the visual modality can help to reduce the risk of visual overload. The driving simulator study (N=24) compared an AWS based on additional steering wheel angle control (Car Gestures) with a visual warning presented in a simulated head-up display (HUD). Both types of warning were activated 3.5s before the hazard object was reached. An additional condition of unassisted driving completed the experimental design. The subjects encountered potential hazards in a variety of urban situations (e.g. a pedestrian standing on the curbs). For the investigated situations, subjective ratings show that a majority of drivers prefer visual warnings over haptic information via gestures. An analysis of driving behavior indicates that both warning approaches guide the vehicle away from the potential hazard. Whereas gestures lead to a faster lateral driving reaction (compared to HUD warnings), the visual warnings result in a greater safety benefit (measured by the minimum distance to the hazard object). A controllability study with gestures in the wrong direction (i.e. leading toward the hazard object) shows that drivers are able to cope with wrong haptic warnings and safety is not reduced compared to unassisted driving as well as compared to (correct) haptic gestures and visual warnings. PMID- 26264519 TI - Serum matrix metalloproteinase-9 in colorectal cancer family-risk population screening. AB - Matrix metalloproteinase-9 (MMP-9) is related to tumour development and progression in colorectal cancer (CRC) and its utility as biomarker has been suggested. The aim of our study was to measure serum MMP-9 in asymptomatic first degree relatives of CRC patients, and to analyse its diagnostic accuracy for the detection of advanced neoplasia (AN: advanced adenomas and CRC). Additionally, we compared its diagnostic capability with the most used non-invasive faecal immunochemical test (FIT). Serum MMP-9 was quantified by ELISA in 516 asymptomatic individuals that underwent a colonoscopy and a FIT. MMP-9 levels were significantly related to age and gender and therefore the concentration was corrected by these confounders. Corrected MMP-9 (cMMP-9) levels were higher in individuals with advanced adenomas (AA; p-value = 0.029) and AN (p-value = 0.056) compared to individuals with no neoplasia. Moreover, elevated cMMP-9 concentration was associated with more severe characteristics of adenomas (number of lesions, size and histology). Nevertheless, the diagnostic accuracy of cMMP-9 was considerably lower than that of FIT for identifying AA (22.64% vs. 47.17% sensitivity, 90% specificity) or AN (19.30% vs. 52.63% sensitivity, 90% specificity). According to our results, serum MMP-9 cannot be considered of utility for the diagnosis of AN in CRC family-risk population screening. PMID- 26264520 TI - Pyrroloquinoline quinone (PQQ) is reduced to pyrroloquinoline quinol (PQQH2) by vitamin C, and PQQH2 produced is recycled to PQQ by air oxidation in buffer solution at pH 7.4. AB - Measurements of the reaction of sodium salt of pyrroloquinoline quinone (PQQNa2) with vitamin C (Vit C) were performed in phosphate-buffered solution (pH 7.4) at 25 degrees C under nitrogen atmosphere, using UV-vis spectrophotometry. The absorption spectrum of PQQNa2 decreased in intensity due to the reaction with Vit C and was changed to that of pyrroloquinoline quinol (PQQH2, a reduced form of PQQ). One molecule of PQQ was reduced by two molecules of Vit C producing a molecule of PQQH2 in the buffer solution. PQQH2, thus produced, was recycled to PQQ due to air oxidation. PQQ and Vit C coexist in many biological systems, such as vegetables, fruits, as well as in human tissues. The results obtained suggest that PQQ is reduced by Vit C and functions as an antioxidant in biological systems, because it has been reported that PQQH2 shows very high free-radical scavenging and singlet-oxygen quenching activities in buffer solutions. PMID- 26264521 TI - Profile of cytokines in the lungs of BALB/c mice after intra-nasal infection with Histoplasma capsulatum mycelial propagules. AB - The host pulmonary response to the fungus Histoplasma capsulatum was evaluated, through the profile of cytokines detected by the MagPix magnetic beads platform in lung homogenates and by lung-granulomas formation, from mice intra-nasally infected with mycelial propagules (M-phase) of two virulent H. capsulatum strains, EH-46 and G-217B. Results highlight that mice lung inflammatory response depends on the H. capsulatum strain used, during the first step of the fungal infection. IL-1beta and TNF-alpha increased their concentrations in mice infected with both strains. The highest levels of IL-6, IL-17, and IL-23 were found in EH 46-infected mice, whereas levels of IL-22 were variable at all post-infection times for both strains. Significant increases of IL-12, IFN-gamma, IL-4, and IL 10 were associated to EH-46-infected mice. Histological lung findings from EH-46 infected mice revealed incipient and numerous well-developed granulomas, distributed in lung-lobes at the 14th and the 21st days after infection, according to cytokine profiles. PMID- 26264522 TI - Intestinal pathogens, diarrhoea and acute phase proteins in naturally infected dairy calves. AB - In this study, the association between Eimeria spp. related signs and innate immune response in dairy calves was examined. Calves (n=100) aged 15-60 days were clinically examined and faecal samples, blood samples and deep nasopharyngeal swabs obtained. The samples were analysed for intestinal pathogens, acute phase proteins and WBC count, and respiratory tract pathogens, respectively. Diarrhoea was diagnosed in 32.6% (23.3-43.0%, 95% CI) of calves. An association between the pathogenic Eimeria spp. and diarrhoea was detected by multiple correspondence analysis. Eimeria related signs (diarrhoea, presence of pathogenic species and total oocyst count) were combined resulting a four level variable. Calves with weak signs of eimeriosis had decreased haptoglobin concentrations (p=0.02) and increased fibrinogen concentrations (p=0.048) compared to no signs. Increased haptoglobin and fibrinogen concentrations were associated with respiratory tract infection and umbilical infection. Serum amyloid A and WBC counts showed no association with signs of eimeriosis or clinical diagnoses. PMID- 26264523 TI - Presence of antibodies to Salmonella in tuatara (Sphenodon punctatus) sera. AB - Colonisation of a host by pathogenic microorganisms is a near constant threat to the health of all vertebrates and most species have evolved an efficient adaptive immune response which produces antibodies following exposure to a specific antigen. The strength of this response can be influenced by many factors including sex and season. Tuatara are exposed to Salmonella through contact with infected skinks and soil; however, no gastrointestinal colonisation of tuatara with Salmonella has been found. Using Western blot and flow cytometry we have demonstrated that tuatara possess antibodies which recognise Salmonella antigens, but many of these antibodies are not specific and are cross-reactive with two closely related and ubiquitous bacteria, Escherichia coli and Citrobacter koseri. Our study describes the anti-Salmonella immune responses in tuatara and will help to inform decisions around maintaining wildlife health, as well as providing important insights into the role and development of adaptive immunity in reptilian species. PMID- 26264524 TI - Experimental infection of chicken embryos with recently described Brucella microti: Pathogenicity and pathological findings. AB - Brucellae are facultative intracellular pathogens causing disease in a wide range of domestic and wild animals as well as in humans. Brucella (B.) microti is a recently recognized species and was isolated from common voles (Microtus arvalis), red foxes and soil in Austria and the Czech Republic. Its pathogenicity for livestock and its zoonotic potential has not been confirmed yet. In the present study 25 SPF chicken embryos were inoculated at day 11 of age with 1.6*10(3) and 1.6*10(5)B. microti by yolk sac and allantoic sac routes. Re isolation of B. microti indicated rapid multiplication of bacteria (up to 1.7*10(12)CFU). B. microti provoked marked gross lesions, i.e. hemorrhages and necroses. All inoculated embryos were dead (100% mortality) in between 2nd and 4th day post inoculation. The predominant histopathological lesion was necroses in liver, kidneys, lungs, spleen, gastrointestinal tract, spinal meninges, yolk sac and chorioallantoic membrane. Immunohistochemical examination showed the presence of Brucella antigen in nearly all of these organs, with infection being mainly restricted to non-epithelial cells or tissues. This study provides the first results on the multiplication and pathogenicity of the mouse pathogenic B. microti in chicken embryos. These data suggest that, even though chicken are not mammals, they could provide a useful tool for understanding the pathogenesis of B. microti associated disease. PMID- 26264525 TI - Reversible stimulus-responsive Cu(I) iodide pyridine coordination polymer. AB - We present a structurally flexible copper-iodide-pyridine-based coordination polymer showing drastic variations in its electrical conductivity driven by temperature and sorption of acetic acid molecules. The dramatic effect on the electrical conductivity enables the fabrication of a simple and robust device for gas detection. X-ray diffraction studies and DFT calculations allow the rationalisation of these observations. PMID- 26264526 TI - Tip-enhanced Raman spectroscopy of bradykinin and its B2 receptor antagonists adsorbed onto colloidal suspended Ag nanowires. AB - The tip-enhanced Raman scattering (TERS) spectra of bradykinin (BK) and its potent B2 BK receptor antagonists, [d-Arg(0),Hyp(3),Thi(5,8),l-Pip(7)]BK and [d Arg(0),Hyp(3),Thi(5),d-Phe(7),l-Pip(8)]BK, approximately with a size of about 40 nm, adsorbed onto colloidal suspended Ag nanowires with diameter in the range of 350-500 nm and length of 2-50 MUm were recorded. The metal surface plasmon resonance and morphology of the Ag nanowires were studied by ultraviolet-visible (UV-Vis) spectroscopy and scanning electron microscopy (SEM). Briefly, it was shown that two C-terminal amino acids of BK and [d-Arg(0),Hyp(3),Thi(5,8),l Pip(7)]BK are involved in the interaction with the colloidal suspended Ag nanowire surface, whereas three last amino acids of the [d-Arg(0),Hyp(3),Thi(5),d Phe(7),l-Pip(8)]BK sequence attached the Ag surface. Thus, BK adsorbs on the colloidal suspended Ag nanowires mainly through the Phe(5/8) ring (tilted orientation) and the one oxygen atom of the carboxylate group and the H2N-C-NH CH2- fragment of Arg(9). In the case of [d-Arg(0),Hyp(3),Thi(5,8),l-Pip(7)]BK, the Thi(8) ring (through the lone electron pair on the sulfur atom) and the both oxygen atoms of the carboxylate group and the amine group of Arg(9) mainly participated in the interaction with the Ag nanowire surface. For [d Arg(0),Hyp(3),Thi(5),d-Phe(7),l-Pip(8)]BK, the d-Phe(7) ring, the Pip(8) ring, and the Arg(9) side-chain assisted in the peptide interaction with the Ag surface. The obtained results emphasize the importance of the C-terminal part of these peptides in the adsorption process onto the colloidal suspended Ag nanowires. PMID- 26264527 TI - Airway management of ruptured pulmonary artery "Rasmussen" aneurysm and massive hemoptysis. AB - BACKGROUND: Pulmonary tuberculosis is caused by Mycobacterium tuberculosis and its manifestations may include parenchymal, airway, vascular, pleural, mediastinal and chest wall lesions. Hemoptysis is a common complication of the disease. Massive hemoptysis occurs in about 8% of cases; with associated mortality ranging from 5 to 25% Massive hemoptysis secondary to pulmonary artery aneurysm rupture is a rare phenomenon presenting unique challenges in airway management and stabilization of oxygenation, ventilation and blood pressure. CASE HISTORY: We present a case of a patient with necrotizing pulmonary tuberculosis complicated by a ruptured pulmonary artery "Rasmussen" aneurysm requiring emergent intubation and embolization. CONCLUSION: Massive hemoptysis should be treated as a medical emergency requiring the coordinated care of multiple specialists including intensivists, interventional radiologists, anesthesiologists, and surgeons. Airway management and stabilization of cardiorespiratory status should be the highest priority, followed by timely diagnostic procedures to localize the site and cause of the bleeding. PMID- 26264528 TI - Flow-enhanced solution printing of all-polymer solar cells. AB - Morphology control of solution coated solar cell materials presents a key challenge limiting their device performance and commercial viability. Here we present a new concept for controlling phase separation during solution printing using an all-polymer bulk heterojunction solar cell as a model system. The key aspect of our method lies in the design of fluid flow using a microstructured printing blade, on the basis of the hypothesis of flow-induced polymer crystallization. Our flow design resulted in a ~90% increase in the donor thin film crystallinity and reduced microphase separated donor and acceptor domain sizes. The improved morphology enhanced all metrics of solar cell device performance across various printing conditions, specifically leading to higher short-circuit current, fill factor, open circuit voltage and significantly reduced device-to-device variation. We expect our design concept to have broad applications beyond all-polymer solar cells because of its simplicity and versatility. PMID- 26264530 TI - Rh(III)-catalyzed cyclization reaction of azoles with alkynes: efficient synthesis of azole-fused-pyridines. AB - A Rh(iii)-catalyzed cyclization of azoles with alkynes has been developed. A variety of azole-fused-pyridines were obtained in good to excellent yields and regioselectivity. Both the C5 and the C4 position of azoles were suitable for the reaction. PMID- 26264529 TI - Isolation and identification of a new neo-clerodane diterpenoid from Teucrium chamaedrys L. AB - Teucrium chamaedrys L. is an aromatic and medicinal plant used as traditional medicine. Aerial parts of the plant material were dried and extracted with hexane dichloromethane (extract 1), ethyl acetate-dichloromethane (extract 2) and methanol-dichloromethane (extract 3) in a ratio of 1:1 at rt successively. The solvents were evaporated to give crude extracts. Extract 1 was suspended in water at 60 degrees C then partitioned successively with hexane and ethyl acetate to give hexane and ethyl acetate portions. After the column chromatography (silica gel) of ethyl acetate extract, one new and four known compounds were isolated. The new compound was named as 1(12S,18R)-15,16-epoxy-2beta,6beta-dihydroxy-neo cleroda-13(16),14-dien-20,l2-olide-l8,l9-hemiacetal (teuchamaedryn D) (4). The known compounds were teucrin A (1), dihydroteugin (2), teucroxide (3), syspirensin A (5). The chromatographic methods were also applied for extract 3 to isolate verbascoside (6) and teucrioside (7). The structure of isolated compounds was elucidated by spectroscopic methods including LC-TOF/MS, 1D NMR and 2D NMR. PMID- 26264531 TI - Acitretin-induced spiny follicular hyperkeratosis. AB - Spiny follicular hyperkeratosis (SFH) is follicular flesh-colored hyperkeratotic spicules that are linked to different situations including drug reactions. Previously suspected drugs are BRAF inhibitors and cyclosporine. We described a 51-year-old psoriasis patient with SFH who had been using acitretin. PMID- 26264532 TI - The effectiveness and reliability of posterior sub-Tenon triamcinolone acetonide injection in branch retinal vein occlusion-related macular edema. AB - OBJECTIVE: To investigate the effectiveness and reliability of posterior sub Tenon triamcinolone acetonide (PSTA) application in branch retinal vein occlusion (BRVO)-related macular edema. METHODS: Patients with confirmed BRVO-related macular edema were enrolled in the study. Patients were injected with a single, therapeutic dose of 40 mg PSTA. Detailed ophthalmic examination was performed at baseline and at 1, 3 and 6 months after the treatment. Best corrected visual acuity (BCVA), intraocular pressure (IOP), cataractogenic change (CC) and macular optical coherence tomography (OCT) analysis results were evaluated. The results were compared statistically. RESULTS: Forty-one eyes of 41 patients with a mean age of 63.49 +/- 10.99 (55-86) years, 15 (36.6%) females, were included in the study. BCVA in LogMAR values at 1 and 3 months were significantly better than at baseline, while no significant difference from baseline was observed in sixth month values (p < 0.001, p < 0.001 and p = 0.846, respectively). Central macular thickness values obtained using OCT were significantly lower at the first, third and sixth months compared to baseline (p < 0.001 for all). IOP elevation was determined in only two eyes (4.8%) at the end of the study period, and no CC was detected in any case. CONCLUSION: PSTA application is an effective and safe option in BRVO-related macular edema. PMID- 26264533 TI - The short-term and long-term adverse ocular effects of fesoterodine fumarate. AB - AIM: To evaluate the short-term and long-term effects of fesoterodine fumarate treatment which is used for overactive bladder (OAB) on pupil diameter (PD), intraocular pressure (IOP) and accommodation amplitude (AA). METHOD: Ophthalmic examination was performed before and after receiving medication (on the 30th and 90th day) on 120 eyes of 120 women whom were planned to begin anticholinergic treatment (fesoterodine fumarate, 4 mg/day, peroral) for OAB, prospectively. The changes in PD, IOP and AA were analyzed statistically. RESULTS: The mean age of 120 women was 52.06 +/- 9.39 years (30-70 years). The mean PD, IOP and AA values were 4.12 +/- 0.61 mm (3.00-5.70 mm), 15.58 +/- 1.74 mmHg (11-20 mmHg) 2.28 +/- 1.26 Diopter (D) (0.50-5.50 D) at baseline; 4.68 +/- 0.65 mm (3.20-5.80 mm), 16.11 +/- 1.72 mmHg (11-20 mmHg), 1.68 +/- 1.04 D (0.25-4.50 D) at 30th day; and 4.28 +/- 0.58 mm (3.10-5.70 mm), 16.09 +/- 1.96 mmHg (11-19 mmHg), 2.18 +/- 1.19 D (0.50-5.00 D) at 90th day, respectively. Although increases in PD values and decreases in AA values were statistically significant (p < 0.001 for each), the changes in IOP values were not as such (p = 0.642). Visual complaint was not observed in any patient. DISCUSSION: The newest anticholinergic medication in women with OAB increased the PD and decreased the AA statistically significantly. Clinically, it seems to be well-tolerated by the patient. PMID- 26264534 TI - Erlotinib-related keratopathy in a patient underwent laser in situ keratomileusis. AB - Erlotinib is a tyrosine kinase inhibitor of the epidermal growth factor receptor. Since there is a wide expression of the epidermal growth factor receptors in the epithelial tissues of ocular surface and adnexa, ocular adverse reactions may happen during systemic administration of erlotinib. Previously reported ocular adverse reactions of erlotinib include trichomegaly, periorbital rash, ectropion, blepharitis, persistent corneal epithelial defect, corneal ulcer and perforation. We report the first case of erlotinib-related keratopathy in a patient who had received laser in situ keratomileusis. The patient presented a special picture of flap striae related to erlotinib. Improvement of keratopathy after cessation of erlotinib was demonstrated. PMID- 26264535 TI - The role of emotion transition for the perception of social dominance and affiliation. AB - Individuals who show anger are rated as higher in dominance and lower in affiliation, whereas those who express sadness are rated lower in dominance and higher in affiliation. Little is known about situations where people show both expressions in sequence as happens when a first emotional reaction is followed by a second, different one. This question was examined in two studies. Overall, we found that the last emotion shown had a strong impact on perceived behavioural intentions. However, the information about the previously shown emotion was also integrated. The specific mode of integration was dependent on the salience of the change and naive theories about the type of person who changes their emotion in the face of changing events. PMID- 26264536 TI - With this issue we mark the passing of Philip F. Barretta. Introduction. PMID- 26264537 TI - Obituary. PMID- 26264538 TI - A Special Moment of Wisdom. PMID- 26264539 TI - Hypnosis Treatment of Gastrointestinal Disorders: A Comprehensive Review of the Empirical Evidence. AB - Hypnotherapy has been investigated for 30 years as a treatment for gastrointestinal (GI) disorders. There are presently 35 studies in the published empirical literature, including 17 randomized controlled trials (RCTs) that have assessed clinical outcomes of such treatment. This body of research is reviewed comprehensively in this article. Twenty-four of the studies have tested hypnotherapy for adult irritable bowel syndrome (IBS) and 5 have focused on IBS or abdominal pain in children. All IBS hypnotherapy studies have reported significant improvement in gastrointestinal symptoms, and 7 out of 10 RCTs in adults and all 3 RCTs in pediatric patient samples found superior outcomes for hypnosis compared to control groups. Collectively this body of research shows unequivocally that for both adults and children with IBS, hypnosis treatment is highly efficacious in reducing bowel symptoms and can offer lasting and substantial symptom relief for a large proportion of patients who do not respond adequately to usual medical treatment approaches. For other GI disorders the evidence is more limited, but preliminary indications of therapeutic potential can be seen in the single randomized controlled trials published to date on hypnotherapy for functional dyspepsia, functional chest pain, and ulcerative colitis. Further controlled hypnotherapy trials in those three disorders should be a high priority. The mechanisms underlying the impact of hypnosis on GI problems are still unclear, but findings from a number of studies suggest that they involve both modulation of gut functioning and changes in the brain's handling of sensory signals from the GI tract. PMID- 26264540 TI - Alert Hypnotic Inductions: Use in Treating Combat Post-Traumatic Stress Disorder. AB - Alert hypnosis can be a valuable part of the treatment protocol for the resolution of post-traumatic stress disorder (PTSD). Research indicates that combat veterans with PTSD are more hypnotically susceptible than the general population. For that reason, it is hypothesized that they should be better able to use hypnosis in treatment. As opposed to the traditional modality, eyes-open alert hypnosis allows the patient to take advantage of hypnotic phenomena while participating responsibly in work, social life, and recreation. Three case studies are reported on combat veterans with PTSD who learned to overcome their symptoms using alert hypnosis. PMID- 26264541 TI - Transcultural Factors in Hypnotizability Scales: Limits and Prospects. AB - Hypnotic suggestibility--loosely termed hypnotizability--is difficult to assess across cultures. Investigators often use translated research instruments to guide their inquiry in disparate geographic locations. Present-day hypnosis researchers rely heavily on two primary scales that are more than half a century old: the Stanford Hypnotic Susceptibility Scale: Form C (SHSS:C) (Weitzenhoffer & Hilgard, 1959) and the Harvard Group Scale of Hypnotic Susceptibility: Form A (HGSHS:A) (Shor & Orne, 1962). Scholars typically translate these scales to measure hypnotizability transculturally. This approach, however, operates under the specious assumption that the concept of hypnotizability is largely monolithic or universal across cultures. Whereas translations likely conserve the linguistic content, they may arguably imply different cultural meanings and historical subtexts. Whereas social scientists acknowledge the importance of qualitative and phenomenological accounts in the study of altered consciousness, including suggestibility, researchers interested in hypnotizability consider the impact of findings from anthropology and ethnography too little. Clinicians and scholars of hypnosis would stand to benefit from incorporating the insights afforded by transcultural research in the overarching investigation of a concept as nuanced as hypnotizability. PMID- 26264542 TI - Hypnosis for Asthma and Vocal Cord Dysfunction in a Patient With Autism. AB - Wheezing in children often is the result of asthma, but vocal cord dysfunction (VCD) may cause stridor or sounds that sometimes are misattributed to the wheezing of asthma. The frequent comorbidity of asthma and VCD also adds to the difficulty in making a clear diagnosis. The challenges of evaluating and treating wheezing are complicated further in children with developmental disorders, such as autism, because of the difficulties of obtaining an adequate history and assessing the clinical response to treatment. This article presents a patient with multiple psychiatric problems, including autism, with severe recurrent wheezing as a result of vocal cord dysfunction and asthma. Hypnosis has previously proven efficacious for treating vocal cord dysfunction, and in this case, hypnotic techniques were major factors in successful symptom control. PMID- 26264543 TI - Effects of Dry Flotation Restricted Environmental Stimulation on Hypnotizability and Pain Control. AB - The effects of dry flotation restricted environmental stimulation (REST) on hypnotizability and pain control were tested in lighted and unlighted conditions. Participants (N = 30, ages 18-30) were exposed to hypnosis maximizing (plateauing) experiences prior to the experiment. Participants were exposed to 6 hours of lighted REST (N = 10), 6 hours of unlighted REST (N = 10), or 6 hours of normal stimulation (N = 10). The Stanford Hypnotic Susceptibility Scale: Form C (SHSS: C) (Weitzenhoffer & Hilgard, 1962) and standardized ischemic pain tests were administered before and after the conditions and at a 2-week follow-up. Both REST groups shared significantly higher SHSS: C scores and significantly lower pain scores from pre-test to post-test and follow-up. The lighted REST group showed significantly higher SHSS: C scores and significantly lower pain scores than the unlighted REST group at post-test and follow-up. The findings supported Barabasz's (1982) theory of REST responding. PMID- 26264544 TI - Successful Treatment of Ptyalism Gravidarum With Concomitant Hyperemesis Using Hypnosis. AB - Ptyalism gravidarum, or sialorrhea, is the excessive secretion of saliva during pregnancy. Treatment of ptyalism gravidarum is often challenging due to its unknown etiologies. This article discusses a case of ptyalism gravidarum with concomitant hyperemesis in which the condition was successfully treated with hypnosis. A 28-year-old woman presented with ptyalism 2 months into her pregnancy and hyperemesis 3 months into pregnancy with associated vomiting that occurred following every meal. Hypnosis was administered at week 16 of pregnancy to eliminate ptyalism and hyperemesis, to prepare for childbirth, and to increase overall psychological well-being. Ptyalism resolved by week 36, concurrent with the final hypnosis session. PMID- 26264548 TI - A FISH-based chromosome map for the European corn borer yields insights into ancient chromosomal fusions in the silkworm. AB - A significant feature of the genomes of Lepidoptera, butterflies and moths, is the high conservation of chromosome organization. Recent remarkable progress in genome sequencing of Lepidoptera has revealed that syntenic gene order is extensively conserved across phylogenetically distant species. The ancestral karyotype of Lepidoptera is thought to be n=31; however, that of the most well studied moth, Bombyx mori, is n=28, and diverse studies suggest that three chromosomal fusion events occurred in this lineage. To identify the boundaries between predicted ancient fusions involving B. mori chromosomes 11, 23 and 24, we constructed fluorescence in situ hybridization (FISH)-based chromosome maps of the European corn borer, Ostrinia nubilalis (n=31). We first determined a 511 Mb genomic sequence of the Asian corn borer, O. furnacalis, a congener of O. nubilalis, and isolated bacterial artificial chromosomes and fosmid clones that were expected to localize in candidate regions for the boundaries using these sequences. Combined with FISH and genetic analysis, we narrowed down the candidate regions to 40 kb-1.5 Mb, in strong agreement with a previous estimate based on the genome of a butterfly, Melitaea cinxia. The significant difference in the lengths of the candidate regions where no functional genes were observed may reflect the evolutionary time after fusion events. PMID- 26264549 TI - Two recently sequenced vertebrate genomes are contaminated with apicomplexan species of the Sarcocystidae family. AB - This paper highlights a general problem, namely that host genome sequences can easily be contaminated with parasite sequences, thus careful isolation of genetic material and careful bioinformatics analysis are needed in all cases. Two recently published genomes are shown here to be contaminated with sequences of apicomplexan parasites which belong to the Sarcocystidae family. Sequences of the characteristic apicomplexan organelle, the apicoplast, were used as queries in BLASTN searches against nucleotide sequences of various animal groups looking for possible contamination. Draft genomes of a bird, Colinus virginianus (Halley et al., 2014), and a bat, Myotis davidii (Zhang et al., 2013) were found to contain at least six and 17 contigs, respectively, originating from the apicoplast of an apicomplexan species, and other genes specific to this phylum can also be found in the published genomes. Obviously, the sources of the genetic material, the muscle and the kidney of the animals, respectively, contained the parasitic cysts. Phylogenetic analyses using 18S rRNA and internal transcribed spacer 1 genes show that the parasite contaminating C. virginianus is a species of Sarcocystis related to ones known to cycle between avian and mammalian hosts. In the case of M. davidii it belongs to the Nephroisospora genus, the only member of which, Nephroisospora eptesici, has been recently identified from the kidney of big brown bats (Eptesicus fuscus). PMID- 26264550 TI - Dietary counselling has no effect on cardiovascular risk factors among Chinese Grade 1 hypertensive patients: a randomized controlled trial. AB - AIMS: To evaluate the effectiveness of Dietary Approaches to Stop Hypertension (DASH) by one-off dietary counselling on reducing cardiovascular risk factors among Chinese Grade 1 hypertensive patients in primary care. METHODS AND RESULTS: A parallel-group, randomized controlled trial (ChiCTR-TRC-13003014) was conducted among patients (40-70 years old) newly diagnosed with Grade 1 hypertension in primary care settings in Hong Kong. Subjects were randomized to usual care (standard education, control) (n = 275), or usual care plus DASH-based dietary counselling (intervention) (n = 281). The study endpoints included blood pressure (BP), lipid profile, and body mass index (BMI) at 6- and 12-months. Outcome data were available for 504 (90.6%) and 485 (87.2%) patients at 6 and 12 months, respectively. Blood pressure levels reduced in both groups at follow-ups. However, the intervention group did not show a significantly greater reduction in either systolic BP (-0.7 mmHg, 95%CI -3.0-1.5 at 6-month; -0.1 mmHg, 95%CI -2.4 2.2 at 12-month) or diastolic BP (-1.0 mmHg, 95%CI -2.7-0.7 at 6-month; -1.1 mmHg, 95%CI -2.9-0.6 at 12-month), when compared with the control group. The improvements in lipid profile and BMI were observed among all subjects, yet no significant differences were detected between intervention and control groups. CONCLUSION: The DASH diet by one-off dietitian counselling which resembled the common primary care practice might confer no added long-term benefits on top of physician's usual care in optimizing cardiovascular risk factors. Physicians may still practice standard usual care, yet further explorations on different DASH delivery models are warranted to inform best clinical practice. PMID- 26264551 TI - Ivabradine and the SIGNIFY conundrum. PMID- 26264553 TI - Circulating microRNAs as biomarkers for diagnosis of early hepatocellular carcinoma associated with hepatitis B virus. AB - Hepatocarcinogenesis is a multistep process that evolves from cirrhosis or dysplastic nodule (DN), and eventually leads to overt hepatocellular carcinoma (HCC). Differentiation between early HCC and DN is an important issue in the clinical setting. This study aims to investigate the potential of circulating microRNA (miRNA) levels in the diagnosis of early HCC. RNA was extracted from sera of 30 chronic hepatitis B patients with pathologically proven DN and 120 age and sex-matched patients with early HCC. Paired samples were collected from ten patients with DN who developed overt HCC in the follow-up. A panel of ten cancer associated miRNAs was analyzed by quantitative real-time reverse-transcription polymerase chain reaction. Serum levels of miR-16, miR-122, miR-221, let-7b and miR-15b were significantly lower in patients with DN than in the HCC group. When DN progressed to overt HCC, serum miR-122, miR-let-7b and miR-15b levels increased significantly (p = 0.046, 0.043 and 0.044, respectively). As a single marker, alpha-fetoprotein (AFP) and miR-122 as well as let-7b had the similar performance for differentiate HCC from DN. As limited to subjects with normal AFP, let-7b resulted in a sensitivity of 84.8% and a specificity of 50% in separating HCC and DN with a cutoff value of 3.5 (p = 0.001). In conclusion, miR 122 and let-7b, which are upregulated in the serum of early-HCC patients, can be useful markers for differentiating early HCC from DN in chronic hepatitis B patients. PMID- 26264555 TI - Glucokinase activation is beneficial or toxic to cultured rat pancreatic islets depending on the prevailing glucose concentration. AB - In rat pancreatic islets, beta-cell gene expression, survival, and subsequent acute glucose stimulation of insulin secretion (GSIS) are optimally preserved by prolonged culture at 10 mM glucose (G10) and markedly altered by culture at G5 or G30. Here, we tested whether pharmacological glucokinase (GK) activation prevents these alterations during culture or improves GSIS after culture. Rat pancreatic islets were cultured 1-7 days at G5, G10, or G30 with or without 3 MUM of the GK activator Ro 28-0450 (Ro). After culture, beta-cell apoptosis and islet gene mRNA levels were measured, and the acute glucose-induced increase in NAD(P)H autofluorescence, intracellular calcium concentration, and insulin secretion were tested in the absence or presence of Ro. Prolonged culture of rat islets at G5 or G30 instead of G10 triggered beta-cell apoptosis and reduced their glucose responsiveness. Addition of Ro during culture differently affected beta-cell survival and glucose responsiveness depending on the glucose concentration during culture: it was beneficial to beta-cell survival and function at G5, detrimental at G10, and ineffective at G30. In contrast, acute GK activation with Ro increased the glucose sensitivity of islets cultured at G10 but failed at restoring beta-cell glucose responsiveness after culture at G5 or G30. We conclude that pharmacological GK activation prevents the alteration of beta-cell survival and function by long-term culture at G5 but mimics glucotoxicity when added to G10. The complex effects of glucose on the beta-cell phenotype result from changes in glucose metabolism and not from an effect of glucose per se. PMID- 26264552 TI - Reduced appropriate implantable cardioverter-defibrillator therapy after cardiac resynchronization therapy-induced left ventricular function recovery: a meta analysis and systematic review. AB - AIMS: For patients undergoing cardiac resynchronization therapy (CRT) with implantable cardioverter-defibrillator (ICD; CRT-D), the effect of an improvement in left ventricular ejection fraction (LVEF) on appropriate ICD therapy may have significant implications regarding management at the time of ICD generator replacement. METHODS AND RESULTS: We conducted a meta-analysis to determine the effect of LVEF recovery following CRT on the incidence of appropriate ICD therapy. A search of multiple electronic databases identified 709 reports, of which 6 retrospective cohort studies were included (n = 1740). In patients with post-CRT LVEF >=35% (study n = 4), the pooled estimated rate of ICD therapy (5.5/100 person-years) was significantly lower than patients with post-CRT LVEF <35% [incidence rate difference (IRD): -6.5/100 person-years, 95% confidence interval (95% CI): -8.8 to -4.2, P < 0.001]. Similarly, patients with post-CRT LVEF >=45% (study n = 4) demonstrated lower estimated rates of ICD therapy (2.3/100 person-years) compared with patients without such recovery (IRD: 5.8/100 person-years, 95% CI: -7.6 to -4.0, P < 0.001). Restricting analysis to studies discounting ICD therapies during LVEF recovery (study n = 3), patients with LVEF recovery (>=35 or >=45%) had significantly lower rates of ICD therapy compared with patients without such recovery (P for both <0.001). Patients with primary prevention indication for ICD, regardless of LVEF recovery definition, had very low rates of ICD therapy (0.4 to 0.8/100-person years). CONCLUSION: Recovery of LVEF post-CRT is associated with significantly reduced appropriate ICD therapy. Patients with improvement of LVEF >=45% and those with primary prevention indication for ICD appear to be at lowest risk. PMID- 26264556 TI - Dynamics of glucose-induced insulin secretion in normal human islets. AB - The biphasic pattern of glucose-induced insulin secretion is altered in type 2 diabetes. Impairment of the first phase is an early sign of beta-cell dysfunction, but the underlying mechanisms are still unknown. Their identification through in vitro comparisons of islets from diabetic and control subjects requires characterization and quantification of the dynamics of insulin secretion by normal islets. When perifused normal human islets were stimulated with 15 mmol/l glucose (G15), the proinsulin/insulin ratio in secretory products rapidly and reversibly decreased (~50%) and did not reaugment with time. Switching from prestimulatory G3 to G6-G30 induced biphasic insulin secretion with flat but sustained (2 h) second phases. Stimulation index reached 6.7- and 3.6-fold for the first and second phases induced by G10. Concentration dependency was similar for both phases, with half-maximal and maximal responses at G6.5 and G15, respectively. First-phase response to G15-G30 was diminished by short (30-60 min) prestimulation in G6 (vs. G3) and abolished by prestimulation in G8, whereas the second phase was unaffected. After 1-2 days of culture in G8 (instead of G5), islets were virtually unresponsive to G15. In both settings, a brief return to G3 G5 or transient omission of CaCl2 restored biphasic insulin secretion. Strikingly, tolbutamide and arginine evoked immediate insulin secretion in islets refractory to glucose. In conclusion, we quantitatively characterized the dynamics of glucose-induced insulin secretion in normal human islets and showed that slight elevation of prestimulatory glucose reversibly impairs the first phase, which supports the view that the similar impairment in type 2 diabetic patients might partially be a secondary phenomenon. PMID- 26264557 TI - Implementation of a patient blood management monitoring and feedback program significantly reduces transfusions and costs. AB - BACKGROUND: Patient blood management (PBM) measures have been shown to be effective in reducing transfusions while maintaining patient outcome. The issuance of transfusion guidelines is seen as being key to the success of PBM programs. As the introduction of guidelines alone did not visibly reduce transfusions in our center, a monitoring and feedback program was established. The aim of our study was to show the effectiveness of such measures in reducing transfusions and cost. STUDY DESIGN AND METHODS: We designed a prospective, interventional cohort study with a 3-year time frame (January 1, 2012 to December 31, 2014). In total, 101,794 patients aged 18 years or older were included. The PBM monitoring and feedback program was introduced on January 1, 2014, with the subsequent issuance of quarterly reporting. RESULTS: Within the first year of introduction, transfusion of all allogeneic blood products per 1000 patients was reduced by 27% (red blood cell units, -24%; platelet units, -25%; and fresh frozen plasma units, -37%; all p < 0.001) leading to direct allogeneic blood product related savings of more than 2 million USD. The number of blood products transfused per case was significantly reduced from 9 +/- 19 to 7 +/- 14 (p < 0.001). With an odds ratio of 0.86 (95% confidence interval, 0.82-0.91), the introduction of our PBM monitoring and feedback program was a significant independent factor in the reduction of transfusion probability (p < 0.001). CONCLUSION: Our PBM monitoring and feedback program was highly efficacious in reducing the transfusion of allogeneic blood products and transfusion-related costs. PMID- 26264558 TI - Deterring driving under the influence of cannabis. PMID- 26264559 TI - leBIBIQBPP: a set of databases and a webtool for automatic phylogenetic analysis of prokaryotic sequences. AB - BACKGROUND: Estimating the phylogenetic position of bacterial and archaeal organisms by genetic sequence comparisons is considered as the gold-standard in taxonomy. This is also a way to identify the species of origin of the sequence. The quality of the reference database used in such analyses is crucial: the database must reflect the up-to-date bacterial nomenclature and accurately indicate the species of origin of its sequences. DESCRIPTION: leBIBI(QBPP) is a web tool taking as input a series of nucleotide sequences belonging to one of a set of reference markers (e.g., SSU rRNA, rpoB, groEL2) and automatically retrieving closely related sequences, aligning them, and performing phylogenetic reconstruction using an approximate maximum likelihood approach. The system returns a set of quality parameters and, if possible, a suggested taxonomic assigment for the input sequences. The reference databases are extracted from GenBank and present four degrees of stringency, from the "superstringent" degree (one type strain per species) to the loosely parsed degree ("lax" database). A set of one hundred to more than a thousand sequences may be analyzed at a time. The speed of the process has been optimized through careful hardware selection and database design. CONCLUSION: leBIBI(QBPP) is a powerful tool helping biologists to position bacterial or archaeal sequence commonly used markers in a phylogeny. It is a diagnostic tool for clinical, industrial and environmental microbiology laboratory, as well as an exploratory tool for more specialized laboratories. Its main advantages, relatively to comparable systems are: i) the use of a broad set of databases covering diverse markers with various degrees of stringency; ii) the use of an approximate Maximum Likelihood approach for phylogenetic reconstruction; iii) a speed compatible with on-line usage; and iv) providing fully documented results to help the user in decision making. PMID- 26264561 TI - Hybrid Diphenylalkyne-Dipeptide Oligomers Induce Multistrand beta-Sheet Formation. AB - Functionalized diphenylalkynes provide a template for the presentation of protein like surfaces composed of multistrand beta-sheets. The conformational properties of three-, four-, and seven-stranded systems have been investigated in the solid- and solution-state. This class of molecule may be suitable for the mediation of therapeutically relevant protein-protein interactions. PMID- 26264560 TI - Maternal group B Streptococcus and the infant gut microbiota. AB - Early patterns of gut colonization may predispose children to adult disease. Exposures in utero and during delivery are associated with the infant gut microbiome. Although ~35% of women carry group B strep (GBS; Streptococcus agalactiae) during pregnancy, it is unknown if GBS presence influences the infant gut microbiome. As part of a population-based, general risk birth cohort, stool specimens were collected from infant's diapers at research visits conducted at ~1 and 6 months of age. Using the Illumina MiSeq (San Diego, CA) platform, the V4 region of the bacterial 16S rRNA gene was sequenced. Infant gut bacterial community compositional differences by maternal GBS status were evaluated using permutational multivariate analysis of variance. Individual operational taxonomic units (OTUs) were tested using a zero-inflated negative binomial model. Data on maternal GBS and infant gut microbiota from either 1 (n=112) or 6-month-old stool (n=150) specimens was available on 262 maternal-child pairs. Eighty women (30.5%) were GBS+, of who 58 (72.5%) were given intrapartum antibiotics. After adjusting for maternal race, prenatal antifungal use and intrapartum antibiotics, maternal GBS status was statistically significantly associated with gut bacterial composition in the 6 month visit specimen (Canberra R 2=0.008, P=0.008; Unweighted UniFrac R 2=0.010, P=0.011). Individual OTU tests revealed that infants of GBS+ mothers were significantly enriched for specific members of the Clostridiaceae, Ruminococcoceae, and Enterococcaceae in the 6 month specimens compared with infants of GBS- mothers. Whether these taxonomic differences in infant gut microbiota at 6 months lead to differential predisposition for adult disease requires additional study. PMID- 26264562 TI - Lycopene reduces cholesterol absorption through the downregulation of Niemann Pick C1-like 1 in Caco-2 cells. AB - SCOPE: Elevated blood cholesterol is an important risk factor associated with atherosclerosis and coronary heart disease. Tomato lycopene has been found to have a hypocholesterolemic effect, and the effect was considered to be related to inhibition of cholesterol synthesis. However, since plasma cholesterol levels are also influenced by the absorption of cholesterol in the gut, the present study is to investigate whether lycopene affects cholesterol absorption in the intestinal Caco-2 cells. METHODS AND RESULTS: The Caco-2 cells were pretreated with lycopene at different concentrations for 24 h and then incubated with radioactive micellar cholesterol for 2 h. The absorption of radioactive cholesterol was quantified by liquid scintillation. The expression of Niemann-Pick C1-like 1 (NPC1L1) and liver X receptor alpha (LXRalpha) was analyzed by Western blot and qPCR. We found that lycopene dose dependently inhibited cholesterol absorption and the expression of NPC1L1 protein and NPC1L1 mRNA. The inhibitory effects of lycopene on cholesterol absorption and NPC1L1 expression could be prevented by blockade of the LXRalpha pathway. CONCLUSION: This study provides the first evidence that lycopene inhibits cholesterol absorption in the intestinal cells and this inhibitory effect of lycopene is mediated, at least in part, by LXRalpha-NPC1L1 signaling pathway. PMID- 26264564 TI - Toward teleoperated needle steering under continuous MRI guidance for prostate percutaneous interventions. AB - BACKGROUND: To propose a human-operated in-room master-slave bevel-tip needle steering system under continuous MRI guidance for prostate biopsy, in which the patient is kept in the scanner at all times and the process of needle placement is under continuous control of the physician. METHODS: A 2-DOF MRI-compatible needle steering module is developed and integrated with an existing 4-DOF transperineal robot, creating a 6-DOF robotic platform for prostate interventions. An MRI-compatible 2-DOF master robot is also developed to enable remote needle steering. An MRI-compatible 2-DOF force/torque sensor was used on the master side. Bevel-tip needle steering is implemented in order to compensate for the targeting error due to needle-tissue interaction. RESULTS: MRI compatibility results demonstrated maximum 20% loss in signal to noise ratio (SNR). Robot functionality was not influenced by the magnetic field. Targeting error was reduced from 4.2 mm to 0.9 mm as a result of bevel-tip needle steering. CONCLUSIONS: The feasibility of teleoperated bevel-tip needle steering using the proposed system was shown in a phantom experiment. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26264565 TI - Developments and advances concerning the hyperpolarisation technique SABRE. AB - To overcome the inherent sensitivity issue in NMR and MRI, hyperpolarisation techniques are used. Signal Amplification By Reversible Exchange (SABRE) is a hyperpolarisation technique that utilises parahydrogen, a molecule that possesses a nuclear singlet state, as the source of polarisation. A metal complex is required to break the singlet order of parahydrogen and, by doing so, facilitates polarisation transfer to analyte molecules ligated to the same complex through the J-coupled network that exists. The increased signal intensities that the analyte molecules possess as a result of this process have led to investigations whereby their potential as MRI contrast agents has been probed and to understand the fundamental processes underpinning the polarisation transfer mechanism. As well as discussing literature relevant to both of these areas, the chemical structure of the complex, the physical constraints of the polarisation transfer process and the successes of implementing SABRE at low and high magnetic fields are discussed. PMID- 26264563 TI - Abnormal connexin expression in human chronic wounds. AB - BACKGROUND: Regulated alteration of connexin expression has been shown to be integral to acute wound repair. Downregulation of the gap-junction protein connexin 43 at the wound edge has been correlated with keratinocyte and fibroblast migration, while abnormal overexpression of connexin 43 significantly perturbs healing, as shown in the streptozotocin diabetic rodent impaired healing model. OBJECTIVES: To examine the protein expression levels of connexin 43, in addition to connexins 26 and 30, in a variety of human chronic wounds. METHODS: Wound-edge punch biopsies and a matched control from the arm were taken from a cohort of patients with venous leg, diabetic foot or pressure ulcers. Wound connexin expression in each patient was compared with that in a matched, nonwounded arm punch. Tissue was sectioned, stained and imaged by confocal microscopy using identical parameters per patient to permit quantification. RESULTS: Epidermal connexin 43, connexin 26 and connexin 30, and dermal connexin 43 were discovered to be strikingly upregulated in every ulcer from all three wound types, pointing to connexin upregulation as a common feature between chronic wounds. CONCLUSIONS: This result supports efforts to target connexin 43 to promote cell migration and wound healing in chronic ulcers. PMID- 26264566 TI - Nitric oxide regulates antagonistically phagocytic and neurite outgrowth inhibiting capacities of microglia. AB - Traumatic injury or the pathogenesis of some neurological disorders is accompanied by inflammatory cellular mechanisms, mainly resulting from the activation of central nervous system (CNS) resident microglia. Under inflammatory conditions, microglia up-regulate the inducible isoform of NOS (iNOS), leading to the production of high concentrations of the radical molecule nitric oxide (NO). At the onset of inflammation, high levels of microglial-derived NO may serve as a cellular defense mechanism helping to clear the damaged tissue and combat infection of the CNS by invading pathogens. However, the excessive overproduction of NO by activated microglia has been suggested to govern the inflammation mediated neuronal loss causing eventually complete neurodegeneration. Here, we investigated how NO influences phagocytosis of neuronal debris by BV-2 microglia, and how neurite outgrowth of human NT2 model neurons is affected by microglial derived NO. The presence of NO greatly increased microglial phagocytic capacity in a model of acute inflammation comprising lipopolysaccharide (LPS)-activated microglia and apoptotic neurons. Chemical manipulations suggested that NO up regulates phagocytosis independently of the sGC/cGMP pathway. Using a transwell system, we showed that reactive microglia inhibit neurite outgrowth of human neurons via the generation of large amounts of NO over effective distances in the millimeter range. Application of a NOS blocker prevented the LPS-induced NO production, totally reversed the inhibitory effect of microglia on neurite outgrowth, but reduced the engulfment of neuronal debris. Our results indicate that a rather simple notion of treating excessive inflammation in the CNS by NO synthesis blocking agents has to consider functionally antagonistic microglial cell responses during pharmaceutic therapy. PMID- 26264567 TI - Society for Paediatric and Perinatal Epidemiology 2015 Annual Meeting: Present and Future. PMID- 26264568 TI - Consumption of Fish and Long-Chain n-3 Polyunsaturated Fatty Acids During Pregnancy: has the Tide Turned? PMID- 26264569 TI - Anti-inflammatory effects of Sanguisorbae Radix on contact dermatitis induced by dinitrofluorobenzene in mice. AB - OBJECTIVE: To investigate the anti-inflflammatory effects of Sanguisorbae Radix on contact dermatitis (CD). METHODS: Mice were sensitized by painting 30 uL of 1 fluoro-2,4-dinitrofluorobenzene (DNFB) onto each ear for 3 days. Four days later, mice were challenged by painting with 50 uL of DNFB onto the shaved dorsum every 2 days. Sanguisorbae Radix methanol extract (MESR) was applied onto the shaved dorsum every 2 days. The effects of MESR on skin thickness, skin weights, histopathological changes, skin lesions and cytokine production in DNFB-induced CD mice were investigated, as well as its effects on body weights and spleen/body weight ratio. RESULTS: Topical application of MESR effectively inhibited enlargement of skin thickness and weight (P<0.05). MESR treatment also inhibited hyperplasia, spongiosis and immune cell infiltration induced by DNFB in inflamed tissues and improved lesions on dorsum skin in CD mice. Moreover, treatment with MESR suppressed the increase in the levels of tumor necrosis factor alpha (TNF alpha,P<0.01) and interferon gamma (IFN-gamma,P<0.05), respectively. Finally, MESR had no effect on body weight gain or spleen/body weight ratio. CONCLUSION: These data suggest that MESR acts as an anti-inflflammatory agent that decreases the production of TNF-alpha and IFN-gamma, resulting in reductions of skin lesions and histopathological changes in inflamed skin tissues. PMID- 26264570 TI - The application status of Chinese herbal medicine in military health service in China. AB - Military medicine has had a long history in China since the emergence of the war. Chinese medicine, especially Chinese herbs, was widely used in China as well as other Asian countries for the prevention and treatment of diseases in the military for hundreds of years. However, the use of Chinese medicine in military health service has never been well studied. In this article, we briefly summarize the application status of Chinese herbal medicine in military health service in China, putting particular emphasis on special military environment, in an attempt to build a bridge between Chinese medicine and military health service and promote the quality of health service for the military and maintain world peace. PMID- 26264571 TI - Shen-Fu Injection () alleviates post-resuscitation myocardial dysfunction by up regulating expression of sarcoplasmic reticulum Ca(2+)-ATPase. AB - OBJECTIVE: To compare the effect of Shen-Fu Injection (SFI) and epinephrine on the expression of sarcoplasmic reticulum Ca(2+) ATPase 2a (SERCA2a) in a pig model with post-resuscitation myocardial dysfunction. METHODS: Ventricular fibrillation (VF) was electrically induced in Wu-zhi-shan miniature pigs. After 8 min of untreated VF and 2 min of cardiopulmonary resuscitation (CPR), all animals were randomly administered a bolus injection of saline placebo (SA group, n=10), SFI (0.8 mg/kg, SFI group, n=10) or epinephrine (20 MUg/kg, EPI group, n=10). After 4 min of CPR, a 100-J shock was delivered. If the defibrillation attempt failed to attain restoration of spontaneous circulation (ROSC), manual chest compressions were rapidly resumed for a further 2 min followed by a second defibrillation attempt. Hemodynamic variables were recorded, and plasma concentrations of catecholamines were measured. Adenylate cyclase (AC), cyclic adenosine monophosphate (cAMP) and the expressions of beta1-adrenoceptor (AR) and SERCA 2a were determined. RESULTS: Cardiac output, left ventricular dp/dtmax and negative dp/dtmax were significantly higher in the SFI group than in the SA and EPI groups at 4 and 6 h after ROSC. The expression of beta1-AR and SERCA2a at 24 h after ROSC were significantly higher in the SFI group than in the SA and EPI groups (P<0.05 or P<0.01). CONCLUSIONS: The administration of epinephrine during CPR decreased the expression of SERCA2a and aggravated postresuscitation myocardial function (P<0.01). SFI attenuated post-resuscitation myocardial dysfunction, and the mechanism might be related to the up-regulation of SERCA2a expression. PMID- 26264572 TI - Effects on the tumor specific growth factor and tumor necrosis factor alpha in rats' precancerous lesion of primary hepatocellular carcinoma by direct moxibustion at Ganshu (BL 18) acupoint. AB - OBJECTIVE: To investigate the effect of direct moxibustion at Ganshu (BL18) on the serum concentrations of tumor specific growth factor (TSGF) and tumor necrosis factor alpha (TNF-alpha) in a rat model with precancerous lesion of primary hepatocellular carcinoma (HCC), so as to explore the mechanism of moxibustion underlying improvement of HCC. METHODS: Sixty male Wistar rats were randomly divided into control group (n=10), model group (n=20), prevention group 1 (n=15) and prevention group 2 (n=15). The normal rats were injected with physiological saline as blank control. At the same time, the rats of other three groups were injected with diethylnitrosamine to establish the HCC model. Direct moxibustion with grain-sized moxa was applied to bilateral Ganshu acupoint of the rats in the prevention group 1 (1 treatment course, 20 days) and prevention group 2 (2 treatment courses, 40 days), 5 doses for each acupoint, 0.5 mg/dose, once every other day. At each time point (before model establishment, the end of 1st course prevention, the end of 2nd course prevention and the end of model establishment), serum levels of TSGF and TNF-alpha were detected using enzyme linked immunosorbent assay. RESULTS: Compared with the control group, there was a remarkably increase of serum TSGF and TNF-alpha contents in the model group at the end of the experiment (P<0.05). At the end of the 1st course of direct moxibustion, the contents of serum TSGF and TNF-alpha of rats in the prevention group 1 were significantly increased compared with that of the model group (P<0.05). At the end of the 2nd course of direct moxibustion, serum TSGF and TNF alpha levels of rats in the model group were higher than the normal group with significantly difference (P<0.05), and the levels of TSGF and TNF-alpha in the prevention group 2 were significantly reduced in comparison with the model group (P<0.05). CONCLUSION: It was possible that direct moxibustion could inhibit precancerous lesion and postpone hepatocarcinogenesis, and the therapeutic effect of two courses were better than one course. PMID- 26264573 TI - Effects of agkistrodon in different dosage forms on collagen-induced arthritis in rats. AB - OBJECTIVE: To determine the effective dosage and formulation of agkistrodon in collagen-induced arthritis (CIA) rats. METHODS: CIA was induced by injection of collagen in complete/incomplete Freund's adjuvant. Agkistrodon decoction, agkistrodon powder, and agkistrodon wine were administered daily starting from the onset of arthritis. Paw swelling degree was measured by using a volume measuring instrument every 7 days after primary immunization. Arthritis index was measured and calculated using the "five scoring method" every 7 days. The levels of serum interleukin-1beta (IL-1beta) and type II collagen IgG antibodies were detected by enzyme-linked immunosorbent assay. Finally, all ankles were removed, and X-ray radiography was performed with In-vivo Imaging System FX. Samples were counterstained with hematoxylin and eosin for analysis. RESULTS: Among the various dosage formulations of agkistrodon, high-dose powder, which was equivalent to an amount of 6 g/day in adults, showed better effects on the inhibition of joint swelling and reduction of arthritis index score. The relatively low levels of serum IL-1 and anti-type II collagen IgG antibodies, as well as the X-ray radiography and pathology results, further proved the superiority of the high-dose powder over the other formulations. The effect of decoction on inhibiting joint swelling was inversely proportional to the dosage. Other effects, such as reduction of arthritis index score and the levels of serum IL-1 and anti-type II collagen IgG antibodies, were directly proportional to the dosage. While the use of large dose agkistrodon wine led to negative effects. CONCLUSION: These data highlight the potential function of high-dose agkistrodon powder, which was equivalent to an amount of 6 g/day in adults. The powder can quickly relieve the symptoms of rheumatoid arthritis and prevent aggravation of disease, especially during the early period. PMID- 26264574 TI - Cornel iridoid glycoside reduces infarct size measured by magnetic resonance imaging and improves neurological function after focal cerebral ischemia in rats. AB - OBJECTIVE: To investigate the effect of cornel iridoid glycoside (CIG), an ingredient extracted from traditional Chinese herb Cornus offificinalis, on neurological function and infarct size in rats as measured by magnetic resonance imaging (MRI) after ischemic stroke. METHODS: Sprague-Dawley rats were divided into three group: control (n=11), model (n=20) and CIG (n=16) groups. Rats in the model and CIG groups underwent 90-min middle cerebral artery occlusion (MCAO) followed by reperfusion. Their neurological defect was measured by using a modified neurological severity score (mNSS). T2-weighted MRI (T2-MRI) of the brain was performed in vivo from 2 to 28 days after MCAO. The infarct volume in the brain was also measured using 2,3,5-triphenyltetrazolium chloride (TTC) staining 28 days after stroke. RESULTS: CIG, 60 mg/(kg day), administered by oral gavage starting from 6 h after the onset of MCAO improved neurological function at 7, 14, 21, and 28 days post occlusion (P<0.05 orP<0.01) and decreased mortality. The infarct volumes computed from the T2-MR images were reduced in the CIG-treated group compared with the model group at 7, 14 and 28 days after MCAO (P<0.05); and the rate at which the infarct volume decreased from 2 to 28 days was higher in the CIG-treated group than that in the model group (P<0.05). The infarct volumes measured by TTC staining were also decreased 28 days after stroke (P<0.05). CONCLUSION: CIG treatment, starting from 6 h after MCAO, reduced infarct size in the brain as measured by MRI and improved neurological function 2 28 days after focal cerebral ischemia in rats, suggesting that CIG could be a clinical application in improving stroke treatment. PMID- 26264575 TI - Structural insights into aberrant cortical morphometry and network organization in psychogenic erectile dysfunction. AB - Functional neuroimaging studies have revealed abnormal brain dynamics of male sexual arousal (SA) in psychogenic erectile dysfunction (pED). However, the neuroanatomical correlates of pED are still unclear. In this work, we obtained cortical thickness (CTh) measurements from structural magnetic resonance images of 40 pED patients and 39 healthy control subjects. Abnormalities in CTh related to pED were explored using a scale space search based brain morphometric analysis. Organizations of brain structural covariance networks were analyzed as well. Compared with healthy men, pED patients showed significantly decreased CTh in widespread cortical regions, most of which were previously reported to show abnormal dynamics of male SA in pED, such as the medial prefrontal, orbitofrontal, cingulate, inferotemporal, and insular cortices. CTh reductions in these areas were found to be significantly correlated with male sexual functioning degradation. Moreover, pED patients showed decreased interregional CTh correlations from the right lateral orbitofrontal cortex to the right supramarginal gyrus and the left angular cortex, implying disassociations between the cognitive, motivational, and inhibitory networks of male SA in pED. This work provides structural insights on the complex phenomenon of psychogenic sexual dysfunction in men, and suggests a specific vulnerability factor, possibly as an extra "organic" factor, that may play an important role in pED. PMID- 26264576 TI - Elucidating the role of the A2A adenosine receptor in neurodegeneration using neurons derived from Huntington's disease iPSCs. AB - Huntington's disease (HD) is an autosomal-dominant degenerative disease caused by a cytosine-adenine-guanine trinucleotide expansion in the Huntingtin (htt) gene. The most vulnerable brain areas to mutant HTT-evoked toxicity are the striatum and cortex. In spite of the extensive efforts that have been devoted to the characterization of HD pathogenesis, no disease-modifying therapy for HD is currently available. The A2A adenosine receptor (A2AR) is widely distributed in the brain, with the highest level observed in the striatum. We previously reported that stimulation of the A2AR triggers an anti-apoptotic effect in a rat neuron-like cell line (PC12). Using a transgenic mouse model (R6/2) of HD, we demonstrated that A2AR-selective agonists effectively ameliorate several major symptoms of HD. In the present study, we show that human iPSCs can be successfully induced to differentiate into DARPP32-positive, GABAergic neurons which express the A2AR in a similar manner to striatal medium spiny neurons. When compared with those derived from control subjects (CON-iPSCs), these HD-iPSC derived neurons exhibited a higher DNA damage response, based on the observed expression of gammaH2AX and elevated oxidative stress. This is a critical observation, because oxidative damage and abnormal DNA damage/repair have been reported in HD patients. Most importantly, stimulation of the A2AR using selective agonists reduced DNA damage and oxidative stress-induced apoptosis in HD-iPSC-derived neurons through a cAMP/PKA-dependent pathway. These findings support our hypothesis that human neurons derived from diseased iPSCs might serve as an important platform to investigate the beneficial effects and underlying mechanisms of A2AR drugs. PMID- 26264577 TI - Repeated low doses of morpholino antisense oligomer: an intermediate mouse model of spinal muscular atrophy to explore the window of therapeutic response. AB - The human SMN2 transgenic mice are well-established models of spinal muscular atrophy (SMA). While the severe type I mouse model has a rapidly progressive condition mimicking type I SMA in humans, the mild type III mice do not faithfully recapitulate chronic SMA variants affecting children. A SMA mouse model that clinically mimics the features of type II and III SMA in human is therefore needed. In this study, we generated intermediately affected SMA mice by delivering low-dose morpholino oligomer (PMO25) into the existing severe SMA mice. We show that a single low-dose administration of PMO25 moderately extended the survival of severe type I SMA mice. The neuromuscular pathology is also modestly but significantly improved in these mice. A second administration of PMO25 at postnatal day 5 (PND5) demonstrated an additive effect on survival. Additional systemic administration of low-dose PMO25 at 2-week intervals suppressed the occurrence of distal necrosis beyond postnatal day 100, and induced more complete phenotypic rescue than a single bolus high-dose injection at PND0. Our study demonstrates that survival of motor neuron (SMN) is required early at a critical threshold to prevent symptoms and suggests that subsequent systemic administration of low-dose PMO25 in SMA mice can provide therapeutic benefit and phenotypic rescue, presumably via peripheral SMN restoration. Our work also provides additional insight into the time window of response to administration of antisense oligonucleotides to SMA mice with an intermediate phenotype. This information is crucial at a time when a number of therapeutic interventions are in clinical trials in SMA patients. PMID- 26264578 TI - Long-term engraftment of myogenic progenitors from adipose-derived stem cells and muscle regeneration in dystrophic mice. AB - Stem cell therapy is a promising approach for treating Duchenne muscular dystrophy (DMD); however, its application is hindered by poor cell engraftment. There have been no reports to date describing the efficient generation of myogenic progenitors from adipose-derived stem cells (ADSCs) that can contribute to muscle regeneration. In this study, we examined the in vivo myogenic potential of progenitors differentiated from ADSCs using forskolin, basic fibroblast growth factor, the glycogen synthase kinase 3beta inhibitor 6-bromoindirubin-3'-oxime as well as the supernatant of ADSC cultures. The results indicate that a proliferative population of myogenic progenitors can be derived from ADSCs that have characteristics similar to muscle satellite cells and are capable of terminal differentiation into multinucleated myotubes. When transplanted into DMD model mdx mice either by intramuscular injection or systemic delivery, progenitors were successfully engrafted in skeletal muscle for up to 12 weeks, and generated new muscle fibers, restored dystrophin expression and contributed to the satellite cell compartment. These findings highlight the potential application of myogenic progenitors derived from ADSCs to the treatment of muscular dystrophy. PMID- 26264579 TI - Altered cytoskeletal organization characterized lethal but not surviving Brtl+/- mice: insight on phenotypic variability in osteogenesis imperfecta. AB - Osteogenesis imperfecta (OI) is a heritable bone disease with dominant and recessive transmission. It is characterized by a wide spectrum of clinical outcomes ranging from very mild to lethal in the perinatal period. The intra- and inter-familiar OI phenotypic variability in the presence of an identical molecular defect is still puzzling to the research field. We used the OI murine model Brtl(+/-) to investigate the molecular basis of OI phenotypic variability. Brtl(+/-) resembles classical dominant OI and shows either a moderately severe or a lethal outcome associated with the same Gly349Cys substitution in the alpha1 chain of type I collagen. A systems biology approach was used. We took advantage of proteomic pathway analysis to functionally link proteins differentially expressed in bone and skin of Brtl(+/-) mice with different outcomes to define possible phenotype modulators. The skin/bone and bone/skin hybrid networks highlighted three focal proteins: vimentin, stathmin and cofilin-1, belonging to or involved in cytoskeletal organization. Abnormal cytoskeleton was indeed demonstrated by immunohistochemistry to occur only in tissues from Brtl(+/-) lethal mice. The aberrant cytoskeleton affected osteoblast proliferation, collagen deposition, integrin and TGF-beta signaling with impairment of bone structural properties. Finally, aberrant cytoskeletal assembly was detected in fibroblasts obtained from lethal, but not from non-lethal, OI patients carrying an identical glycine substitution. Our data demonstrated that compromised cytoskeletal assembly impaired both cell signaling and cellular trafficking in mutant lethal mice, altering bone properties. These results point to the cytoskeleton as a phenotypic modulator and potential novel target for OI treatment. PMID- 26264580 TI - Safe and bodywide muscle transduction in young adult Duchenne muscular dystrophy dogs with adeno-associated virus. AB - The ultimate goal of muscular dystrophy gene therapy is to treat all muscles in the body. Global gene delivery was demonstrated in dystrophic mice more than a decade ago using adeno-associated virus (AAV). However, translation to affected large mammals has been challenging. The only reported attempt was performed in newborn Duchenne muscular dystrophy (DMD) dogs. Unfortunately, AAV injection resulted in growth delay, muscle atrophy and contracture. Here we report safe and bodywide AAV delivery in juvenile DMD dogs. Three ~2-m-old affected dogs received intravenous injection of a tyrosine-engineered AAV-9 reporter or micro-dystrophin (MUDys) vector at the doses of 1.92-6.24 * 10(14) viral genome particles/kg under transient or sustained immune suppression. DMD dogs tolerated injection well and their growth was not altered. Hematology and blood biochemistry were unremarkable. No adverse reactions were observed. Widespread muscle transduction was seen in skeletal muscle, the diaphragm and heart for at least 4 months (the end of the study). Nominal expression was detected in internal organs. Improvement in muscle histology was observed in MUDys-treated dogs. In summary, systemic AAV gene transfer is safe and efficient in young adult dystrophic large mammals. This may translate to bodywide gene therapy in pediatric patients in the future. PMID- 26264581 TI - The wasting continuum in heart failure: from sarcopenia to cachexia. AB - Sarcopenia (muscle wasting) and cachexia share some pathophysiological aspects. Sarcopenia affects approximately 20 %, cachexia <10 % of ambulatory patients with heart failure (HF). Whilst sarcopenia means loss of skeletal muscle mass and strength that predominantly affects postural rather than non-postural muscles, cachexia means loss of muscle and fat tissue that leads to weight loss. The wasting continuum in HF implies that skeletal muscle is lost earlier than fat tissue and may lead from sarcopenia to cachexia. Both tissues require conservation, and therapies that stop the wasting process have tremendous therapeutic appeal. The present paper reviews the pathophysiology of muscle and fat wasting in HF and discusses potential treatments, including exercise training, appetite stimulants, essential amino acids, growth hormone, testosterone, electrical muscle stimulation, ghrelin and its analogues, ghrelin receptor agonists and myostatin antibodies. PMID- 26264582 TI - Superficial temporal artery: the "C" shape half-buttonhole configuration as it courses over the zygomatic arch. AB - PURPOSE: To describe the course and configuration of the superficial temporal artery (STA) around the zygomatic arch. METHODS: Volume rendered 3D reconstructions of computed tomography angiography of 25 healthy patients were performed and analyzed at Duke University Hospitals. RESULTS: The STA coursed over the zygomatic arch or over the condylar process of the mandible in all cases (25/25 pts, 100 %). The STA courses over the posterior zygomatic arch in 23/25 pts (92 %), creating a characteristic "C" shape half-buttonhole configuration as it embraces the arch. When the STA travels posterior to the zygomatic arch, there is no C shape configuration (2/25 pts, 8 %). The STA bifurcates distal to the zygomatic arch in 24/25 pts (96 %). CONCLUSIONS: The "C" shape half-buttonhole configuration is a useful identifying characteristic of the most common course of the STA-over the posterior zygomatic arch before it bifurcates. PMID- 26264583 TI - Bilateral comparison of the vascular pattern of the superficial temporal artery based on digital subtraction angiography. AB - PURPOSE: This study was performed to investigate any bilateral differences in the vascular pattern and microsurgical relevant parameters of the superficial temporal artery (STA) in vivo. METHODS: Digital subtraction angiographies of the STA of 38 individuals were retrospectively analyzed. A bilateral comparison of the branching pattern as well as of surgically relevant diameters and lengths of the main branches of the STA was performed. Moreover, gender-specific differences were assessed. RESULTS: Only 10 cases (26%) demonstrated an identical type and subtype of the STA pattern bilaterally. The diameters of the STA at its origin and bifurcation level as well as of its parietal branch were statistically significant wider on the right than on the left side (p(o) = 0.0009, p(b) = 0.006, p(p) = 0.030). Moreover, the diameters of the STA at its origin level on the right side, at its bifurcation level on both sides and of the frontal branch on both sides were statistically significant wider in males than females. No statistically significant differences of the lengths of the STA and its main branches between the right and the left side were identified. CONCLUSION: The occurrence of the vascular pattern of the STA in vivo is random for each side of the same person and cannot be predicted by the vascular pattern of the opposite side. The calibers of the main branches of the STA are gender specific and commonly larger on the right than on the left side. PMID- 26264585 TI - Tendon grafts: their natural history, biology and future development. AB - The use of tendon grafts has diminished as regimes of primary repairs and rehabilitation have improved, but they remain important in secondary reconstruction. Relatively little is known about the cellular biology of grafts, and the general perception is that they have little biological activity. The reality is that there is a wealth of cellular and molecular changes occurring with the process of engraftment that affect the quality of the repair. This review highlights the historical perspectives and modern concepts of graft take, reviews the different attachment techniques and revisits the biology of pseudosheath formation. In addition, we discuss some of the future directions in tendon reconstruction by grafting, which include surface modification, vascularized tendon transfer, allografts, biomaterials and cell-based therapies. PMID- 26264586 TI - Re: Jordan et al. Surgical adhesive BioGlueTM does not benefit tendon repair strength: an ex vivo study. J Hand Surg Eur. 2015, 40: 700-4. PMID- 26264587 TI - Re: Wada T, Oda T. Mallet fingers with bone avulsion and DIP joint subluxation. J Hand Surg Eur. 2015, 40: 63-7. PMID- 26264590 TI - Long-term effects of neoadjuvant chemoradiotherapy followed by sphincter preserving resection on anal sphincter function in relation to quality of life among locally advanced rectal cancer patients: a cross-sectional analysis. AB - BACKGROUND: There is growing recognition for the consequences of rectal cancer treatment to maintain an adequate functional sphincter in the long-term rather than preserving the anal sphincter itself. This study aims to evaluate long-term effects of neoadjuvant chemoradiotherapy (nCRT) followed by sphincter-preserving resection on anal sphincter function in relation to quality of life (QoL) among locally advanced rectal cancer patients. METHODS: Twenty-nine patients treated with nCRT followed by low anterior resection surgery were included in this study. Data on patient demographics, tumor location and symptoms of urgency and fecal soiling were recorded and evaluated with respect to Wexner Fecal Incontinence Scoring Scale, European Organization for Research and Cancer (EORTC) cancer specific (EORTC QLQ-C30) and colorectal cancer-specific (EORTC QLQ-CR38) questionnaires and anorectal manometrical findings. Correlation of manometrical findings with Wexner Scale, EORTC QLQ-CR38 scores and EORTC QLQ-C30 scores was also evaluated. RESULTS: Median follow-up was 45.6 months (ranged 7.5-98 months. Higher scores for incontinence for gas (p = 0.001), liquid (p = 0.048) and solid (p = 0.019) stool, need to wear pad (p = 0.001) and alteration in life style (p = 0.004) in Wexner scale, while lower scores for future perspective (p = 0.010) and higher scores for defecation problems (p = 0.001) in EORTC QLQ-CR38 were noted in patients with than without urgency. Manometrical findings of resting pressure (mmHg) was positively correlated with body image (r = 0.435, p = 0.030) and sexual functioning (r = 0.479, p = 0.011) items of functional scale, while rectal sensory threshold (RST) volume (mL) was positively correlated with defecation problems (r = 0.424, p = 0.031) items of symptom scale in EORTC QLQ-CR38 and negatively correlated with social function domain (r = -0.479, p = 0.024) in EORTC QLQ-C30. RST volume was also positively correlated with Wexner scores including incontinence for liquid stool (r = 0.459, p = 0.024), need to wear pad (r = 0.466, p = 0.022) and alteration in lifestyle (r = 0.425, p = 0.038). CONCLUSION: The high risk of developing functional anal impairment as well as the systematic registration of not only oncological but also functional and QoL related outcomes seem important in rectal cancer patients in the long-term disease follow-up. PMID- 26264591 TI - In vivo analysis of trypanosome mitochondrial RNA function by artificial site specific RNA endonuclease-mediated knockdown. AB - Trypanosomes possess a unique mitochondrial genome called the kinetoplast DNA (kDNA). Many kDNA genes encode pre-mRNAs that must undergo guide RNA-directed editing. In addition, alternative mRNA editing gives rise to diverse mRNAs and several kDNA genes encode open reading frames of unknown function. To better understand the mechanism of RNA editing and the function of mitochondrial RNAs in trypanosomes, we have developed a reverse genetic approach using artificial site specific RNA endonucleases (ASREs) to directly silence kDNA-encoded genes. The RNA-binding domain of an ASRE can be programmed to recognize unique 8-nucleotide sequences, allowing the design of ASREs to cleave any target RNA. Utilizing an ASRE containing a mitochondrial localization signal, we targeted the extensively edited mitochondrial mRNA for the subunit A6 of the F0F1 ATP synthase (A6) in the procyclic stage of Trypanosoma brucei. This developmental stage, found in the midgut of the insect vector, relies on mitochondrial oxidative phosphorylation for ATP production with A6 forming the critical proton half channel across the inner mitochondrial membrane. Expression of an A6-targeted ASRE in procyclic trypanosomes resulted in a 50% reduction in A6 mRNA levels after 24 h, a time dependent decrease in mitochondrial membrane potential (DeltaPsim), and growth arrest. Expression of the A6-ASRE, lacking the mitochondrial localization signal, showed no significant growth defect. The development of the A6-ASRE allowed the first in vivo functional analysis of an edited mitochondrial mRNA in T. brucei and provides a critical new tool to study mitochondrial RNA biology in trypanosomes. PMID- 26264592 TI - RNA polymerase II CTD phospho-sites Ser5 and Ser7 govern phosphate homeostasis in fission yeast. AB - Phosphorylation of the tandem YSPTSPS repeats of the RNA polymerase II CTD inscribes an informational code that orchestrates eukaryal mRNA synthesis. Here we interrogate the role of the CTD in phosphate homeostasis in fission yeast. Expression of Pho1 acid phosphatase, which is repressed during growth in phosphate-rich medium and induced by phosphate starvation, is governed strongly by CTD phosphorylation status, but not by CTD repeat length. Inability to place a Ser7-PO4 mark (as in S7A) results in constitutive derepression of Pho1 expression in phosphate-replete medium. In contrast, indelible installation of a Ser7-PO4 mimetic (as in S7E) hyper-represses Pho1 in phosphate-replete cells and inhibits Pho1 induction during starvation. Pho1 phosphatase is derepressed by ablation of the CTD Ser5-PO4 mark, achieved either by mutating Ser5 in all consensus heptads to alanine, or replacing all Pro6 residues with alanine. We find that Ser5 status is a tunable determinant of Pho1 regulation, i.e., serial decrements in the number of consensus Ser5 heptads from seven to two elicits a progressive increase in Pho1 expression in phosphate-replete medium. Pho1 is also derepressed by hypomorphic mutations of the CTD kinase Cdk9. Inactivation of the CTD phosphatase Ssu72 attenuates Pho1 induction in wild-type cells and blocks Pho1 derepression in S7A cells. These experiments implicate Ser5, Pro6, and Ser7 as component letters of a CTD coding "word" that transduces a repressive transcriptional signal via serine phosphorylation. PMID- 26264594 TI - Agitation increases expansion of cord blood hematopoietic cells and promotes their differentiation into myeloid lineage. AB - Mechanical stress caused by agitation is one of the factors that can affect hematopoietic stem cell expansion in suspension bioreactors. Therefore, we have investigated the effects of agitation on umbilical cord blood hematopoietic stem cell (UCB-HSC) growth and differentiation. A comparison was made between various agitation rates (20, 40 and 60 rpm) in spinner-flask and cells cultured in glass petri dish as a static culture. Moreover, the fluid dynamic at various agitation rates of spinner-flask was analyzed to determine shear stress. The spinner-flask contained a rotational moving mixer with glass ball and was kept in tissue culture incubator. To reduce consumption of cytokines, UCB-serum was used which widely decreased the costs. Our results determined that, agitation rate at 40 rpm promoted UCB-HSCs expansion and their colony forming potential. Myeloid progenitors were the main type of cells at 40 rpm agitation rate. The results of glucose consumption and lactic acid production were in complete agreement with colony assay and expansion data and indicated the superiority of culture in spinner-flask when agitated at 40 rpm over to other agitation speeds and also static culture. Cell viability and colony count was affected by changing the agitation speed. We assume that changes in cell growth resulted from the effect of shear stress directly on cell viability, and indirectly on signaling pathways that influence the cells to differentiate. PMID- 26264593 TI - Secondary Voice Restoration After Laryngotracheal Separation (LTS) for Dysphagia with Intractable Aspiration. AB - Intractable aspiration is a serious, often life-threatening condition due to its potential impact on pulmonary function. Aspiration requires therapeutic measures, starting with conservative management but often necessitating surgical treatment. The basic surgical principle is to separate the alimentary and respiratory tracts through a variety of procedures which, unfortunately, nearly all result in the loss of phonation, with the exception of total laryngectomy (TL) which includes the placement of an indwelling voice prosthesis. In this study, we present a modified laryngotracheal separation (LTS) technique that, we believe, offers multiple advantages compared to standard TL. After reviewing the medical records of 35 patients with intractable aspiration who have undergone LTS, we describe the surgical technique and present the postoperative result. In a second surgical procedure about two months following LTS, we aimed to achieve voice restoration by placement of an indwelling voice prosthesis. Intractable aspiration was successfully treated in all patients. Placement of an indwelling voice prosthesis during a second operation was successful in 15 patients, representing the largest reported cohort thus far. LTS is a reliable surgical technique to treat intractable aspiration, with restoration of oral intake, thereby improving the general condition and quality of life of these unfortunate patients. Furthermore, voice restoration can be achieved in selected patients, by placement of a voice prosthesis. PMID- 26264595 TI - Establishment and characterization of a Satureja khuzistanica Jamzad (Lamiaceae) cell suspension culture: a new in vitro source of rosmarinic acid. AB - An in vitro approach to the production of rosmarinic acid (RA), a medicinally important caffeic acid ester, in a cell suspension culture (CSC) of Satureja khuzistanica Jamzad (Lamiaceae) has been investigated for the first time. The CSC was established from friable calli derived from shoot tip explants in Gamborg's B5 liquid medium supplemented with 30 g/L sucrose, 20 mg/L L-glutamine, 200 mg/L casein hydrolysate, 5 mg/L benzyladenine (BA) and 1 mg/L indole-3-butyric acid (IBA). The effect of nitrogen source (KNO3 and (NH4)2SO4) and their different concentrations on the fresh and dry weight (g/L), as well as RA content (mg/g dry weight) were measured. CSC growth measurements indicated a maximum specific cell growth rate of 1.5/day, a doubling time of 7.6 days and a high percentage of cell viability (96.4 %) throughout the growth cycle. Maximum cell fresh weight (353.5 g/L), dry weight (19.7 g/L) and RA production (180.0 mg/g) were attained at day 21 of culture. Cell growth and RA content were affected by nitrogen deficiency. Media containing 8.3 mM of total nitrogen (1/4 of B5 standard medium) led to a minimum cell fresh weight (243.0 g/L), dry weight (17.4 g/L) and RA content (38.0 mg/g) after 21 days. The established CSC provided useful material for further optimization experiments aimed at a large-scale production of RA. PMID- 26264596 TI - Therapeutic Potential of Denosumab in Patients With Lung Cancer: Beyond Prevention of Skeletal Complications. AB - Approximately up to 40% of patients with lung cancer develop bone metastasis, with 22% to 59% of them experiencing skeletal-related events (SREs), which result in an important quality of life deterioration and economic burden. Denosumab, a fully human antibody that targets the receptor activator of nuclear factor-kappaB (RANK) ligand (RANKL), is indicated for prevention of SREs in patients with solid tumors and has demonstrated superiority in breast and prostate cancer, and in other solid tumors, in reducing the risk of first SRE by 17% versus zoledronic acid. In the subset of patients with non-small-cell lung carcinoma (NSCLC), denosumab has also shown a positive trend to SRE risk reduction. Denosumab might have direct or indirect antitumor effects. Cancer cells produce factors that stimulate increased bone resorption by osteoclasts, which in turn release tumor growth factors into the bone microenvironment, initiating a tumor/bone vicious cycle. An increasing body of evidence suggests RANK/RANKL signaling plays a role in this tumorigenesis. Both proteins are overexpressed in different tumor types including lung cancer cells. RANK/RANKL signaling activates nuclear factor-kappaB pathways related to lung carcinogenesis and increases intercellular adhesion molecule 1 expression and MEK/extracellular signal-regulated kinase phosphorylation, which in turn enhances tumor cell migration. In animal NSCLC models, denosumab delayed bone metastases and reduced skeletal tumor growth. In patients with lung cancer (post hoc analysis), denosumab prolonged overall survival by 1.2 months versus zoledronic acid (P = .01). This hypothesis generating outcome warrants further investigation and 2 studies in lung cancer are ongoing to elucidate the therapeutic potential of denosumab beyond SRE prevention. PMID- 26264597 TI - Modification of targets related to the Entner-Doudoroff/pentose phosphate pathway route for methyl-D-erythritol 4-phosphate-dependent carotenoid biosynthesis in Escherichia coli. AB - BACKGROUND: In engineered strains of Escherichia coli, bioconversion efficiency is determined by not only metabolic flux but also the turnover efficiency of relevant pathways. Methyl-D-erythritol 4-phosphate (MEP)-dependent carotenoid biosynthesis in E. coli requires efficient turnover of precursors and balanced flux among precursors, cofactors, and cellular energy. However, the imbalanced supply of glyceraldehyde 3-phosphate (G3P) and pyruvate precursors remains the major metabolic bottleneck. To address this problem, we manipulated various genetic targets related to the Entner-Doudoroff (ED)/pentose phosphate (PP) pathways. Systematic target modification was conducted to improve G3P and pyruvate use and rebalance the precursor and redox fluxes. RESULTS: Carotenoid production was improved to different degrees by modifying various targets in the Embden-Meyerhof-Parnas (EMP) and ED pathways, which directed metabolic flux from the EMP pathway towards the ED pathway. The improvements in yield were much greater when the MEP pathway was enhanced. The coordinated modification of ED and MEP pathway targets using gene expression enhancement and protein coupling strategies in the pgi deletion background further improved carotenoid synthesis. The fine-tuning of flux at the branch point between the ED and PP pathways was important for carotenoid biosynthesis. Deletion of pfkAB instead of pgi reduced the carotenoid yield. This suggested that anaplerotic flux of G3P and pyruvate might be necessary for carotenoid biosynthesis. Improved carotenoid yields were accompanied by increased biomass and decreased acetate overflow. Therefore, efficient use of G3P and pyruvate precursors resulted in a balance among carotenoid biosynthesis, cell growth, and by-product metabolism. CONCLUSIONS: An efficient and balanced MEP-dependent carotenoid bioconversion strategy involving both the ED and PP pathways was implemented by the coordinated modification of diverse central metabolic pathway targets. In this strategy, enhancement of the ED pathway for efficient G3P and pyruvate turnover was crucial for carotenoid production. The anaplerotic role of the PP pathway was important to supply precursors for the ED pathway. A balanced metabolic flux distribution among precursor supply, NADPH generation, and by-product pathways was established. PMID- 26264598 TI - Disparities in early death and survival in children, adolescents, and young adults with acute promyelocytic leukemia in California. AB - BACKGROUND: Findings from clinical trials and population-based studies have differed with regard to whether mortality within 30 days of diagnosis (early death) of acute promyelocytic leukemia (APL) has decreased in the era of all trans retinoic acid and anthracycline-based chemotherapy. METHODS: Using data from the California Cancer Registry, the authors investigated 7-day and 30-day mortality and survival in 772 patients who were aged birth to 39 years when they were diagnosed with APL during 1988 to 2011. Logistic regression and Cox proportional models were used to examine the association of early death and survival, respectively, with sociodemographic and clinical factors. RESULTS: The overall 30-day mortality decreased significantly over time, from 26% (1988-1995) to 14% (2004-2011) (P =.004). On multivariable analysis, the odds of 30-day mortality were 3 times as high during 1988 through 1995 than 2004 through 2011 (P =.001). However, 7-day mortality did not improve over time (P =.229). When patients who died within 7 days of diagnosis were excluded, the 30-day mortality during 1996 to 2011 was 3% to 8%, which is similar to levels reported in clinical trials. Higher early death and lower survival were associated with a lack of health insurance (1996-2011) (early death odds ratio, 2.67; P =.031) and Hispanic race/ethnicity (early death odds ratio, 2.13; P =.014). Early death was not found to be associated with age, sex, socioeconomic status, or hospital type. Black patients also experienced worse survival. CONCLUSIONS: The findings of the current study revealed a decreased 30-day mortality during the all-trans retinoic acid era, but 7-day mortality remained high. Efforts to achieve equal outcomes in young patients with APL should focus on improving access to effective treatment, mainly among uninsured patients and those of Hispanic and black race/ethnicity. PMID- 26264599 TI - Increased number of circulating exosomes and their microRNA cargos are potential novel biomarkers in alcoholic hepatitis. AB - BACKGROUND: It has been well documented that alcohol and its metabolites induce injury and inflammation in the liver. However, there is no potential biomarker to monitor the extent of liver injury in alcoholic hepatitis patients. MicroRNAs (miRNAs) are a class of non-coding RNAs that are involved in various physiologic and pathologic processes. In the circulation, a great proportion of miRNAs is associated with extracellular vesicles (EVs)/exosomes. Here, we hypothesized that the exosome-associated miRNAs can be used as potential biomarkers in alcoholic hepatitis (AH). METHODS: Exosomes were isolated from sera of alcohol-fed mice or pair-fed mice, and plasma of alcoholic hepatitis patients or healthy controls by ExoQuick. The exosomes were characterized by transmission electron microscopy and Western blot and enumerated with a Nanoparticle Tracking Analysis system. FireflyTM microRNA Assay was performed on miRNA extracted from mice sera. TaqMan microRNA assay was used to identify differentially expressed miRNAs in plasma of cohort of patients with AH versus controls followed by construction of receiver operating characteristic (ROC) curves to determine the sensitivity and specificity of the candidates. RESULTS: The total number of circulating EVs was significantly increased in mice after alcohol feeding. Those EVs mainly consisted of exosomes, the smaller size vesicle subpopulation of EVs. By performing microarray screening on exosomes, we found nine inflammatory miRNAs which were deregulated in sera of chronic alcohol-fed mice compared to controls including upregulated miRNAs: miRNA-192, miRNA-122, miRNA-30a, miRNA-744, miRNA-1246, miRNA 30b and miRNA-130a. The ROC analyses indicated excellent diagnostic value of miRNA-192, miRNA-122, and miRNA-30a to identify alcohol-induced liver injury. We further validated findings from our animal model in human samples. Consistent with the animal model, total number of EVs, mostly exosomes, was significantly increased in human subjects with AH. Both miRNA-192 and miRNA-30a were significantly increased in the circulation of subjects with AH. miRNA-192 showed promising value for the diagnosis of AH. CONCLUSION: Elevated level of EVs/exosomes and exosome-associated miRNA signature could serve as potential diagnostic markers for AH. In addition to the biomarker diagnostic capabilities, these findings may facilitate development of novel strategies for diagnostics, monitoring, and therapeutics of AH. PMID- 26264601 TI - Kinetic and isotherm study of Sudan black B removal. AB - In this research, the removal of Sudan black B (SBB) by cadmium hydroxide nanowires loaded on activated carbon is described. After optimizing the variables involved, Langmuir, Freundlich, Tempkin, and Dubinin-Radushkevich models were applied to fit the experimental data. The adsorbent correlation coefficient and error analysis indicated the applicability of Langmuir model for the interpretation of equilibrium data. Different kinetic models were applied to analyze the time evolution of removal data. It was found that low quantity of adsorbent (<0.03 g) is capable of removal of large amount of SBB in reasonably short time (<40 min). The adsorption process was found to be described by both pseudo-second-order kinetics and interparticle diffusion mechanism. The effects of variables such as pH, amount of adsorbent, and contact time on batch adsorption process were investigated and optimized. PMID- 26264600 TI - Visceral adipose tissue-derived serine protease inhibitor augments acetylcholine induced relaxation via the inhibition of acetylcholine esterase activity in rat isolated mesenteric artery. AB - AIM: Visceral adipose tissue-derived serine protease inhibitor (vaspin) is an adipocytokine with insulin-sensitizing activity originally identified in visceral adipose tissues of obesity-related type II diabetic rats. We previously showed that vaspin inhibits vascular cell migration and apoptosis as well as inflammatory responses, which are crucial for the development of hypertension. However, little is known about the effects of vaspin on vascular reactivity. The aim of this study was thus to explore the effects of vaspin on contraction and relaxation of isolated blood vessel. METHODS: After mesenteric arteries were isolated from male Wistar rats, the effects of pretreatment with vaspin (3 ng mL( 1) , 30 min) on concentration-contraction and concentration-relaxation relationships for each agent were examined. The effects of vaspin on acetylcholine (ACh)-induced phosphorylation of endothelial nitric oxide (NO) synthase (eNOS) and ACh esterase (AChE) activity were also examined using Western blotting and colorimetric method respectively. RESULTS: Vaspin did not affect noradrenaline- or 5-hydroxytryptamine-induced contraction. In contrast, vaspin augmented ACh- but not histamine-, A23187- or carbachol-induced NO-mediated relaxation. Vaspin significantly increased ACh-induced eNOS phosphorylation and inhibited AChE activity. CONCLUSION: We for the first time demonstrate that vaspin augments the ACh-induced NO-mediated endothelium-dependent relaxation via the inhibition of AChE activity. PMID- 26264602 TI - Comparative study of diseases of the stomatognathic system and specific parameters of osteoporosis. AB - What are the specific parameters of dental health that present with modifications in osteoporosis (OP)? Both OP and a decreased bone mass can affect dental health. A low mineral density may lead to the loss of dentures because the jaw is exposed to the effects of periodontitis and without strong sustainability the teeth may lose their stability. INTRODUCTION: We compared the values of the periodontal index (IP) with a T score for women presenting with OP at menopause and those without OP. We found that there is a relation between OP and the loss of bone mass at the oral-facial level. METHODS: The study included 87 patients, aged between 35 and 75 years. We correlated gums and IP with the T score for the two groups. RESULTS: We found a significant difference between the values of the IP index for the group with OP in comparison with the control group. Thus a correlation between OP and IP was confirmed. CONCLUSIONS: IP was statistically significantly higher in women at menopause with OP than those without OP. Gum retraction was significantly higher in women at menopause with OP than in the control group. There was thus a real correlation between bone mineral density (BMD) and IP, while between BMD and dental mobility we found no correlation. PMID- 26264603 TI - Thyrotropin serum levels are differentially associated with biochemical markers of bone turnover and stiffness in women and men: results from the SHIP cohorts. AB - In two large German population-based cohorts, we showed positive associations between serum thyrotropin (TSH) concentrations and the Fracture Risk Assessment score (FRAX) in men and positive associations between TSH concentrations and bone turnover markers in women. INTRODUCTION: The role of thyroid hormones on bone stiffness and turnover is poorly defined. Existing studies are confounded by differences in design and small sample size. We assessed the association between TSH serum concentrations and bone stiffness and turnover in the SHIP cohorts, which are two population-based cohorts from a region in Northern Germany comprising 2654 men and women and 3261 men and women, respectively. METHODS: We calculated the bone stiffness index using quantitative ultrasound (QUS) at the calcaneus, employed FRAX score for assessment of major osteoporotic fractures, and measured bone turnover markers, N-terminal propeptide of type I procollagen (P1NP), bone-specific alkaline phosphatase (BAP), osteocalcin, and type I collagen cross-linked C-telopeptide (CTX) in all subjects and sclerostin in a representative subgroup. RESULTS: There was no association between TSH concentrations and the stiffness index in both genders. In men, TSH correlated positively with the FRAX score both over the whole TSH range (p < 0.01) and within the reference TSH range (p < 0.01). There were positive associations between TSH concentrations and P1NP, BAP, osteocalcin, and CTX (p < 0.01) in women but not in men. There was no significant association between TSH and sclerostin levels. CONCLUSIONS: TSH serum concentrations are associated with gender-specific changes in bone turnover and stiffness. PMID- 26264604 TI - Diabetes mellitus and risk of hip fractures: a meta-analysis. AB - This meta-analysis revealed that diabetic adults had a twofold greater risk of hip fractures compared with non-diabetic populations, and this association was more pronounced in type 1 diabetes. INTRODUCTION: The relationship between diabetes mellitus and risk of hip fracture yielded conflicting results. We conducted a meta-analysis to investigate the association between diabetes mellitus and the risk of hip fractures based on observational studies. METHODS: We conducted a systematic literature search of PubMed and Embase databases through May 2015. We selected cohort and case-control studies providing at least age-adjusted risk ratio (RR) and corresponding 95 % confidence intervals (CI) of hip fractures among diabetic and non-diabetic subjects. Moreover, we pooled the female-to-male RR of hip fractures from studies that reported gender-specific risk estimate in a single study. RESULTS: Twenty-one studies involving 82,293 hip fracture events among 6,995,272 participants were identified. Diabetes mellitus was associated with an increased risk of hip fractures (RR 2.07; 95 % CI 1.83 2.33) in a random effects model. Subgroup analysis indicated that excess risk of hip fracture was more pronounced in type 1 diabetes (RR 5.76; 95 % CI 3.66-9.07) than that in type 2 diabetes (RR 1.34; 95 % CI 1.19-1.51). The pooled female-to male RR of hip fractures was 1.09 (95 % CI 0.93-1.28). CONCLUSIONS: Individuals with diabetes mellitus have an excessive risk of hip fractures, and this relationship is more pronounced in type 1 diabetes. The association between diabetes and hip fracture risk is similar in men and women. PMID- 26264605 TI - Towards better use of the net reclassification improvement (NRI) index. PMID- 26264606 TI - GATA2 deficiency in children and adults with severe pulmonary alveolar proteinosis and hematologic disorders. AB - BACKGROUND: The majority of cases with severe pulmonary alveolar proteinosis (PAP) are caused by auto-antibodies against GM-CSF. A multitude of genetic and exogenous causes are responsible for few other cases. Goal of this study was to determine the prevalence of GATA2 deficiency in children and adults with PAP and hematologic disorders. METHODS: Of 21 patients with GM-CSF-autoantibody negative PAP, 13 had no other organ involvement and 8 had some form of hematologic disorder. The latter were sequenced for GATA2. RESULTS: Age at start of PAP ranged from 0.3 to 64 years, 4 patients were children. In half of the subjects GATA2-sequence variations were found, two of which were considered disease causing. Those two patients had the typical phenotype of GATA2 deficiency, one of whom additionally showed a previously undescribed feature - a cholesterol pneumonia. Hematologic disorders included chronic myeloic leukemia, juvenile myelo-monocytic leukemia, lymphoblastic leukemia, sideroblastic anemia and two cases of myelodysplastic syndrome (MDS). A 4 year old child with MDS and DiGeorge Syndrome Type 2 was rescued with repetitive whole lung lavages and her PAP was cured with heterologous stem cell transplant. CONCLUSIONS: In children and adults with severe GM-CSF negative PAP a close cooperation between pneumologists and hemato-oncologists is needed to diagnose the underlying diseases, some of which are caused by mutations of transcription factor GATA2. Treatment with whole lung lavages as well as stem cell transplant may be successful. PMID- 26264607 TI - Comparison of end-tidal CO2 measured by transportable capnometer (EMMATM capnograph) and arterial pCO2 in general anesthesia. AB - An end-tidal CO2 monitor (capnometer) is used most often as a noninvasive substitute for PaCO2 in anesthesia, anesthetic recovery, and intensive care. Additionally, the wide spread on-site use of portable capnometers in emergency and trauma situations is now observed. This study was conducted to compare PaCO2 measurement between the EMMATM portable-capnometer and sidestream capnometry. End tidal CO2 (portable capnometer: EMMATM capnograph, side stream capnometry module: Datex-Ohmeda S5 Anesthesia Monitor) levels were recorded at the time of arterial blood gas sampling of patients undergoing general anesthesia. Data were compared using the Bland and Altman method, and by evaluating the clinical significance performed by calculating the percent error (%). A total of 100 data were obtained from 35 patients. The bias of PaCO2 and portable capnometer was 6.0 mmHg, where the upper and lower limits of the agreement were 11.8 and 0.3 mmHg, respectively. The percent error was 18.0 %. The bias of side stream capnometry and portable capnometer was 2.2 mmHg, where the upper and the lower limits of the agreement were 6.0 and -1.6 mmHg, respectively. The percent error was 13.0 %. Significant differences between the PETCO2 and PaCO2 values of the EMMATM portable-capnometer were not observed for patients undergoing general anesthesia. ClinicalTrials.gov identifier NCT02184728. PMID- 26264609 TI - A clinicopathologic study of diencephalic pediatric low-grade gliomas with BRAF V600 mutation. AB - Among brain tumors, the BRAF (V600E) mutation is frequently associated with pleomorphic xanthoastrocytomas (PXAs) and gangliogliomas (GGs). This oncogenic mutation is also detected in ~5 % of other pediatric low-grade gliomas (LGGs) including pilocytic astrocytomas (PAs) and diffuse astrocytomas. In the current multi-institutional study of 56 non-PXA/non-GG diencephalic pediatric LGGs, the BRAF (V600) mutation rate is 36 %. V600-mutant tumors demonstrate a predilection for infants and young children (297 cells/MUL was 12.2 and 35.3 months, respectively (P < 0.001). Patients with post ALC <=698 and >698 cells/MUL had an overall survival of 19.3 and 46.9 months, respectively (P = 0.001). The median overall survival of the lymphopenia (min ALC <= 297 cells/MUL or post ALC <= 698 cells/MUL) and the non-lymphopenia group (min ALC > 297 cells/MUL and post ALC > 698 cells/MUL) was 19.0 and 131.7 months, respectively, while the median progression survival was 8.1 and 16.6 months, respectively (P < 0.001 and P = 0.001). Radiation-related lymphopenia could predict poor survival in LS-SCLC. Its prognostic role should be evaluated in further prospective studies. PMID- 26264619 TI - Vascular endothelial growth factor polymorphisms and a synchronized examination of plasma and tissue expression in epithelial ovarian cancers. AB - In this study, we have analyzed six genetic polymorphisms of the VEGF-A gene and correlated the genetic data with plasma and tissue expression of VEGF-A in epithelial ovarian carcinomas. A total of 130 cases including 95 malignant carcinomas, 17 low malignant potential and 18 benign tumours were studied. rs699947, rs833061, rs1570360, rs2010963, rs1413711 and rs3025039 were studied by polymerase chain reaction and restriction fragment length polymorphism (PCR RFLP). Plasma levels of VEGF-A were estimated by enzyme-linked immunosorbent assay (ELISA) and tissue expression of VEGF-A by immunohistochemistry (IHC). Four polymorphisms of the above excluding rs699947 and rs3025039 showed significant association with malignancy, and we observed the presence of positive correlation between haplotype CCGGCC and increased expression of VEGF-A in both plasma and tissues which also correlated with poor prognosis and recurrence suggesting a probable increase in resistance to treatment in such carriers. Highly upregulated tissue expression of VEGF-A was seen in all epithelial ovarian carcinomas with intensity of expression increasing from benign to malignant cases. ELISA data from our study showed an increase in circulating levels of VEGF-A in malignancies. VEGF-A plasma levels can be employed as a biomarker for high-grade malignancy in epithelial ovarian cancers alongside tissue expression and CA-125 levels. This study is unique due to the fact that a simultaneous analysis of plasma and tissue expression has been demonstrated and is a first such study in epithelial ovarian cancers and representing the Indian population (South-east Asian) synchronized with genetic polymorphism data as well. PMID- 26264620 TI - Reply to: "in vivo post-contrast 1H-MRS evaluation of malignant and benign breast lesions: a meta-analysis". PMID- 26264623 TI - Effects of novel auto-inducible medium on growth, activity and CO2 capture capacity of Escherichia coli expressing carbonic anhydrase. AB - A glucose-based auto-inducible medium (glucose-AIM) has been developed to enhance both growth and expression of lac operon-linked carbonic anhydrase (CA) expression in a recombinant strain of Escherichia coli. When the E. coli expressing CA was grown on various media, the glucose-based auto-inducible medium (glucose AIM) resulted in a CA activity of 1022 mU OD(600 nm)(-1) mL(-1) at 24 h and a specific growth rate of 0.082 h(-1). The CA activity was four to fourteen times higher than those by LB-IPTG. The E. coli expressing CA grown on the glucose-AIM showed highest activity at pH8.5 while it kept high stability up to 40 degrees C and an inlet CO2 concentration of 6%. These findings indicate that the glucose-AIM would be a cost-effective medium to support high cell growth, CA activity and stability for effective CO2 capture. PMID- 26264621 TI - The use of the Godin-Shephard Leisure-Time Physical Activity Questionnaire in oncology research: a systematic review. AB - BACKGROUND: The Godin-Shephard Leisure-Time Physical Activity Questionnaire (GSLTPAQ) is one of the most often used questionnaires in oncology research, yet modifications to the scale are done with little evidence of psychometric testing. This study aimed to (i) document the frequency of use of the questionnaire for ranking (i.e., level of activity) and classification (i.e., active versus insufficiently active) purposes, (ii) summarize how the GSLTPAQ is used in terms of item content and scoring, and (iii) evaluate the extent to which validity evidence supports the use of the scale among cancer survivors. METHODS: A systematic review was conducted with evidence drawn from English-written articles published between January 1(st) 1985 (year the GSLTPAQ was published) and December 31, 2014. A search of six databases, a scan of reference list of included articles, and a cited reference search identified articles that reported using the GSLTPAQ among cancer survivors. RESULTS: A total of 212 articles were retrieved. The GSLTPAQ was used for classifying cancer survivors into active and insufficiently active categories in 51 % of the articles. Moreover, a modified version of the questionnaire was used in 81 % of the research studies. Three studies reported validity evidence based on the relationship between the scores on the GSLTPAQ (i.e., leisure score index, LSI) and accelerometer or pedometer derived activity data. Validity evidence supporting the use of the GSLTPAQ for assessing changes in LSI was computed from six randomized trials. CONCLUSIONS: The use of the GSLTPAQ for classification purpose in oncology research is common. Standardization in the use and interpretation of the GSLTPAQ in oncology research is warranted. Although limited, there is support for using the original form of the GSLTPAQ and interpreting the LSI for ranking cancer survivors from the lowest to highest levels of leisure-time physical activity. PMID- 26264622 TI - A novel pathway of cellular activation mediated by antiphospholipid antibody induced extracellular vesicles. AB - BACKGROUND: Elevated levels of endothelial cell (EC)-derived extracellular vesicles (EVs) circulate in patients with antiphospholipid antibodies (APLAs), and APLAs, particularly those against beta2 -glycoprotein I (beta2 GPI), stimulate EV release from ECs. However, the effects of EC-derived EVs have not been characterized. OBJECTIVE: To determine the mechanism by which EVs released from ECs by anti-beta2 GPI antibodies activate unstimulated ECs. PATIENTS/METHODS: We used interleukin (IL)-1 receptor inhibitors, small interfering RNA (siRNA) against Toll-like receptors (TLRs) and microRNA (miRNA) profiling to assess the mechanism(s) by which EVs released from ECs exposed to anti-beta2 GPI antibodies activated unstimulated ECs. RESULTS AND CONCLUSIONS: Anti-beta2 GPI antibodies caused formation of an EC inflammasome and the release of EVs that were enriched in mature IL-1beta, had a distinct miRNA profile, and caused endothelial activation. However, activation was not inhibited by an IL 1beta antibody, an IL-1 receptor antagonist, or IL-1 receptor siRNA. EC activation by EVs required IL-1 receptor-associated kinase 4 phosphorylation, and was inhibited by pretreatment of cells with TLR7 siRNA or RNase A, which degrades ssRNA. Profiling of miRNA in EVs released from ECs incubated with beta2 GPI and either control IgG or anti-beta2 GPI antibodies revealed numerous differences in the content of specific miRNAs, including a significant decrease in mIR126. These observations demonstrate that, although anti-beta2 GPI-derived endothelial EVs contain IL-1beta, they activate unstimulated ECs through a TLR7-dependent and ssRNA-dependent pathway. Alterations in miRNA content may contribute to the ability of EVs derived from ECs exposed to anti-beta2 GPI antibodies to activate unstimulated ECs in an autocrine or paracrine manner. PMID- 26264624 TI - Cecal drop reflects the chickens' cecal microbiome, fecal drop does not. AB - Microbiota in the gastro-intestinal tract are closely related to both the intestinal and overall health of the host. Experimental chickens have always been euthanized in order to identify and quantify the bacteria in cecal content. In this study, quantification and identification of the microbial populations in cecal drop, cecal content and fecal drop samples from chickens showed that cecal drop contains a bacterial community that is very similar (concerning bacterial diversity, richness and species composition) to cecal content, as opposed to the bacterial community found in fecal drop. Cecal drop analysis thus allows for longitudinal experiments on chickens' cecal bacteria. The varying results in the analysis of fecal samples question the method's reliability in reflecting the true cecal microbiota in chickens. PMID- 26264625 TI - PCR-RFLP on beta-tubulin gene for rapid identification of the most clinically important species of Aspergillus. AB - Aspergillus species are important agents of life-threatening infections in immunosuppressed patients. Proper speciation in the Aspergilli has been justified based on varied fungal virulence, clinical presentations, and antifungal resistance. Accurate identification of Aspergillus species usually relies on fungal DNA sequencing but this requires expensive equipment that is not available in most clinical laboratories. We developed and validated a discriminative low cost PCR-based test to discriminate Aspergillus isolates at the species level. The Beta tubulin gene of various reference strains of Aspergillus species was amplified using the universal fungal primers Bt2a and Bt2b. The PCR products were subjected to digestion with a single restriction enzyme AlwI. All Aspergillus isolates were subjected to DNA sequencing for final species characterization. The PCR-RFLP test generated unique patterns for six clinically important Aspergillus species, including Aspergillus flavus, Aspergillus fumigatus, Aspergillus nidulans, Aspergillus terreus, Aspergillus clavatus and Aspergillus nidulans. The one-enzyme PCR-RFLP on Beta tubulin gene designed in this study is a low-cost tool for the reliable and rapid differentiation of the clinically important Aspergillus species. PMID- 26264627 TI - Problems with sickness certification tasks: experiences from physicians in different clinical settings. A cross-sectional nationwide study in Sweden. AB - BACKGROUND: Many physicians find sickness certification of patients problematic. The aims were to explore problems that physicians in different clinical settings experience with sickness certification tasks in general and with assessment of function, work capacity, and need for sick leave, as well as handling of sick leave spells of different durations. METHODS: Data from a questionnaire sent to 33,144 physicians aged <68 years, living and working in Sweden in 2012 were analysed. The response rate was 57.6%. The study group comprised the 12,933 responders who had sickness certification tasks. Frequencies and odds ratios with 95% confidence intervals were calculated for questions concerning how problematic the physicians experienced different assessments related to patients' function, work capacity, and need for sick leave, as well as handling sick-leave spells of different durations. RESULTS: There were large differences between clinical settings regarding how often and to what extent sickness certification consultations were perceived as problematic. Physicians working in primary health care (PHC) had the highest proportions experiencing sickness certification consultations as problematic at least once a week (49.5%) and as very or fairly problematic (56.6%), followed by physicians working in psychiatry, pain management, or orthopaedics. More than half of the responders found it very or fairly problematic to assess patients' work capacity (57.8%), to make a long-term prognosis about patients' future work capacity (55.7%), and to handle long-term or very long-term sickness certifications (51.9% and 51.8%). The proportions were highest among physicians working in PHC, rheumatology, neurology, or psychiatry. CONCLUSIONS: The rates of physicians finding sickness certification task problematic varied much with clinical setting, and were highest among physicians in PHC. More knowledge is needed about the work conditions and prerequisites for optimal handling of sickness certification in different clinical settings. PMID- 26264628 TI - Continuous Positive Airway Pressure for Motion Management in Stereotactic Body Radiation Therapy to the Lung: A Controlled Pilot Study. AB - OBJECTIVE: To determine the effect of continuous positive airway pressure (CPAP) on tumor motion, lung volume, and dose to critical organs in patients receiving stereotactic body radiation therapy (SBRT) for lung tumors. METHODS AND MATERIALS: After institutional review board approval in December 2013, patients with primary or secondary lung tumors referred for SBRT underwent 4-dimensional computed tomographic simulation twice: with free breathing and with CPAP. Tumor excursion was calculated by subtracting the vector of the greatest dimension of the gross tumor volume (GTV) from the internal target volume (ITV). Volumetric and dosimetric determinations were compared with the Wilcoxon signed-rank test. CPAP was used during treatment if judged beneficial. RESULTS: CPAP was tolerated well in 10 of the 11 patients enrolled. Ten patients with 18 lesions were evaluated. The use of CPAP decreased tumor excursion by 0.5 +/- 0.8 cm, 0.4 +/- 0.7 cm, and 0.6 +/- 0.8 cm in the superior-inferior, right-left, and anterior posterior planes, respectively (P <= .02). Relative to free breathing, the mean ITV reduction was 27% (95% confidence interval [CI] 16%-39%, P<.001). CPAP significantly augmented lung volume, with a mean absolute increase of 915 +/- 432 cm(3) and a relative increase of 32% (95% CI 21%-42%, P=.003), contributing to a 22% relative reduction (95% CI 13%-32%, P=.001) in mean lung dose. The use of CPAP was also associated with a relative reduction in mean heart dose by 29% (95% CI 23%-36%, P=.001). CONCLUSION: In this pilot study, CPAP significantly reduced lung tumor motion compared with free breathing. The smaller ITV, the planning target volume (PTV), and the increase in total lung volume associated with CPAP contributed to a reduction in lung and heart dose. CPAP was well tolerated, reproducible, and simple to implement in the treatment room and should be evaluated further as a novel strategy for motion management in radiation therapy. PMID- 26264629 TI - Single Vocal Cord Irradiation: Image Guided Intensity Modulated Hypofractionated Radiation Therapy for T1a Glottic Cancer: Early Clinical Results. AB - PURPOSE: To report, from a retrospective analysis of prospectively collected data, on the feasibility, outcome, toxicity, and voice-handicap index (VHI) of patients with T1a glottic cancer treated by a novel intensity modulated radiation therapy technique developed at our institution to treat only the involved vocal cord: single vocal cord irradiation (SVCI). METHODS AND MATERIALS: Thirty patients with T1a glottic cancer were treated by means of SVCI. Dose prescription was set to 16 * 3.63 Gy (total dose 58.08 Gy). The clinical target volume was the entire vocal cord. Setup verification was done by means of an online correction protocol using cone beam computed tomography. Data for voice quality assessment were collected prospectively at baseline, end of treatment, and 4, 6, and 12 weeks and 6, 12, and 18 months after treatment using VHI questionnaires. RESULTS: After a median follow-up of 30 months (range, 7-50 months), the 2-year local control and overall survival rates were 100% and 90% because no single local recurrence was reported and 3 patients died because of comorbidity. All patients have completed the intended treatment schedule; no treatment interruptions and no grade 3 acute toxicity were reported. Grade 2 acute dermatitis or dysphagia was reported in only 5 patients (17%). No serious late toxicity was reported; only 1 patient developed temporary grade 2 laryngeal edema, and responded to a short course of corticosteroid. The VHI improved significantly, from 33.5 at baseline to 9.5 and 10 at 6 weeks and 18 months, respectively (P<.001). The control group, treated to the whole larynx, had comparable local control rates (92.2% vs 100%, P=.24) but more acute toxicity (66% vs 17%, P<.0001) and higher VHI scores (23.8 and 16.7 at 6 weeks and 18 months, respectively, P<.0001). CONCLUSION: Single vocal cord irradiation is feasible and resulted in maximal local control rate at 2 years. The deterioration in VHI scores was slight and temporary and subsequently improved to normal levels. Long-term follow-up is needed to consolidate these promising results. PMID- 26264630 TI - Clinical, radiographic, and histologic analysis of the effects of acemannan used in direct pulp capping of human primary teeth: short-term outcomes. AB - Acemannan has been previously reported as a direct pulp-capping agent in animal study. This natural material demonstrated its biocompatibility and enhanced reparative dentin formation. The objective of this study was to investigate the action of acemannan as a direct pulp-capping material in human primary teeth with deep caries. Forty-two deeply carious mandibular primary molars from 37 children, aged 7-11 years old diagnosed with reversible pulpitis were studied. After completely removing the infected dentine, teeth with a pinpoint pulpal exposure were randomly divided into two treatment groups: acemannan or calcium hydroxide. A glass-ionomer cement base was applied to all teeth prior to restoration with stainless steel crowns. Clinical and radiographic evaluation was performed 6 months post-treatment. The teeth due to exfoliate were extracted and histopathologically evaluated for inflammation, dentine bridge formation, and soft tissue organization. At 6 months, the overall clinical and radiographic success rates of direct pulp capping with acemannan and calcium hydroxide at 6 months were 72.73 and 70.0 %, respectively. The histopathological results indicated that the acemannan-treated group had significantly better histopathological responses compared with the calcium hydroxide-treated group (p < 0.05). These data suggest acemannan offers a valuable alternative biomaterial for vital pulp therapy in primary teeth. PMID- 26264631 TI - How a New Health Intervention Affects the Health Systems? Learnings from Pentavalent Vaccine Introduction in India. AB - OBJECTIVES: To summarize the findings from a Post Introduction Evaluation (PIE) of pentavalent vaccine in Tamil Nadu and Kerala state of India and to understand how the health systems could be prepared for (prior to) introducing a new intervention and how such introduction could affect the health systems (afterwards). METHODS: A post introduction evaluation (PIE) of Haemophilus influenzae type b (Hib) as pentavalent (DPT + HepB + Hib) vaccine was conducted in Tamil Nadu and Kerala states of India in July-Aug 2012. The PIE was conducted as per World Health Organization PIE methods and tools specifically adapted for India. This PIE adopted a 'mixed method approach' with qualitative data focus. RESULTS: The planning for the introduction of pentavalent vaccine provided opportunities to strengthen various functions of the health system i.e., piloting of Open Vial Policy, strengthening surveillance system, improving Adverse Events Following Immunization (AEFI) reporting system and formation of the technical expert groups. It provided opportunity for bringing attention on the immunization programme in general as well. After the vaccine introduction, the beneficial effects were noted on stewardship (increased oversight by top level policy makers and programme managers), creating resources (investment and trainings of staff in immunization), service delivery (increased coverage with the vaccines and improved quality of services) and financing (increased financial allocation and reduced out of pocket expenditures as more people started attending public health facilities). The vaccine introduction was found to be associated with improvement in the health equity, efficiency and service utilization (effective coverage). CONCLUSIONS: New vaccine introduction provides opportunities (both before and after) for strengthening the health systems in setting such as India. Preparing the health system for new challenges has potential to strengthen the health systems, if done in well-coordinated and planned manner. Considering that essential steps are largely similar, these lessons could be applicable for the introduction of other new health interventions in the similar settings. PMID- 26264632 TI - Adult Attention Deficit Hyperactivity Disorder and Parenting Styles. AB - The aim of the present study was to compare the parenting styles in parents with and without adult attention deficit hyperactivity disorder (ADHD) who had children with ADHD. It was a case-control study with convenience sampling strategy. Participants were recruited from the parents of previously diagnosed children with ADHD referred to Imam Hossein Hospital, Tehran/ Iran. Ninety parents with adult ADHD and 120 normal parents were chosen by Conner's Adult ADHD Screening Scale (CAARS) and psychiatrist interview. Using Baumrind Parenting Styles Questionnaire and Arnold Parenting Scale, parenting styles were assessed in both the groups. Results from independent samples t-test indicated that Authoritarian parenting style (F = 0.576, p 0.022) and Over reacting style (F = 7.976, p 0.045) were significantly higher in cases. On the other hand, controls were using Permissive style (F = 0.131, p 0.044) more than cases. The results are consistent with prior studies; these findings can improve the content of parent training for children with ADHD, who have adult ADHD themselves. PMID- 26264633 TI - An Outbreak of Burkholderia cepacia Bacteremia in a Neonatal Intensive Care Unit. AB - OBJECTIVES: To identify the source of infection, to study the clinical profile and outcomes of neonates with Burkholderia septicemia and to determine the antimicrobial susceptibility patterns of the isolates. METHODS: The authors describe a 3 mo outbreak of nosocomial Burkholderia cepacia bacteremia involving 12 neonates. During the outbreak, ventilator humidifier water, intravenous solutions and other possible sources were taken from the concerned neonatal intensive care units (NICUs); cultured and isolates identified by standard microbiological techniques and VITEK system. Clinical details of affected babies were also obtained to ascertain the clinical significance of the isolates. RESULTS: All neonates had clinical and biochemical evidence of sepsis and the source could be tracked to intravenous solutions of 5% dextrose, normal saline (opened bottles) and continuous positive airway pressure humidifier water. Strain relatedness of the environmental isolates with the clinical isolates is likely as antibiotic susceptibility patterns were similar. CONCLUSIONS: The investigations revealed the source of the nosocomial outbreak which is crucial for initiating appropriate control measures. PMID- 26264635 TI - Interphalangeal Arthrodesis of the Toe With a New Radiolucent Intramedullary Implant (Toegrip). AB - BACKGROUND: Interphalangeal arthrodesis is a very common surgical treatment of rigid hammertoe and claw toe deformities. The K-wires habitually used in this procedure are sometimes complicated by pin tract infection, migration, discomfort, and breakage. The aim of this study is to evaluate the results of an interphalangeal arthrodesis with a new radiolucent angulated intramedullary implant. METHODS: A total of 377 implants were placed in 297 patients between October 1, 2011, and October 1, 2012. In this study, 157 patients had more than 1 year follow-up and 142 patients were reviewed. The operation technique is explained in detail. RESULTS: This intramedullary device offers a good immediate mechanical stability, adequate deformity correction, and a high rate of consolidation (83%). The satisfaction rate of patients in this series was 94%. CONCLUSIONS: This study demonstrates good results with a new generation of radiolucent implants. LEVEL OF EVIDENCE: Therapeutic, Level IV: Case series. PMID- 26264634 TI - Association of the Apolipoprotein E polymorphism with migraine: a meta-analysis. AB - BACKGROUND: Apolipoprotein E (ApoE) gene has been reported to be associated with migraine and tension-type headache (TTH), but the results are conflicting. This study aimed to evaluate the association of ApoE with migraine by a meta-analysis. METHODS: MEDLINE, ISI Web of Knowledge, The Cochrane Central Register of Controlled Trials, and EMBASE databases were searched to identify eligible studies published in English from 2000 to 2014. Data were extracted using standardized forms. The association was assessed by relative risk (RR) with 95% confidence intervals (CIs) using a fixed or random effects model. RESULTS: Four studies, comprising 649 migraineurs, 229 TTH subjects and 975 controls, met all the criteria and were included in the meta-analysis. No significant difference was found comparing genotypic and allelic frequencies in the case of migraineurs versus controls and TTH subjects versus controls. Only when migraineurs and TTH subjects were considered as a whole group, ApoE4 was found to increase the relative risk of headache by 1.48 (95% CI 1.16, 1.90; P = 0.002), compared to controls. CONCLUSIONS: ApoE epsilon4 allele is not associated with migraine susceptibility, but is positively related to headache (including migraine and TTH). PMID- 26264636 TI - Trends of Concurrent Ankle Arthroscopy at the Time of Operative Treatment of Ankle Fracture: A National Database Review. AB - BACKGROUND: The purpose of this study was to report trends associated with concurrent ankle arthroscopy at the time of operative treatment of ankle fracture. METHOD: The current procedural terminology (CPT) billing codes were used to search the PearlDiver Patient Record Database and identify all patients who were treated for acute ankle fracture in the United States. The Medicare Standard Analytic Files were searchable between 2005 and 2011 and the United Healthcare Orthopedic Dataset from 2007 to 2011. Annual trends were expressed only between 2007 and 2011, as it was the common time period among both databases. Demographic factors were identified for all procedures as well as the cost aspect using the Medicare data set. RESULTS: In total, 32 307 patients underwent open reduction internal fixation (ORIF) of an ankle fracture, of whom 313 (1.0%) had an ankle arthroscopy performed simultaneously. Of those 313 cases, 70 (22.4%) patients received microfracture treatment. Between 2005 and 2011, 85 203 patients were treated for an ankle fracture whether via ORIF or closed treatment. Of these, a total of 566 patients underwent arthroscopic treatment within 7 years. The prevalence of arthroscopy after ankle fracture decreased significantly by 45% from 2007 to 2011 (P< .0001). When ORIF and microfracture were performed concurrently, the total average charge for both procedures drops to $4253.00 and average reimbursement to $818.00 compared with approximately $4964.00 and $1069.00, respectively, when they were performed subsequently. CONCLUSION: Despite good evidence in favor of arthroscopy at the time of ankle fracture treatment, it appears that only a small proportion of surgeons in the United States perform these procedures concurrently. LEVELS OF EVIDENCE: Therapeutic, Level IV: Retrospective. PMID- 26264637 TI - Tibiotalocalcaneal Arthrodesis Using a Nitinol Intramedullary Hindfoot Nail. AB - Tibiotalocalcaneal (TTC) arthrodesis using an intramedullary hindfoot nail is a common procedure for deformity correction and the treatment of combined tibiotalar and subtalar end-stage arthritis. Nonunion at one or both fusion sites is a difficult complication that can result in reoperation, significant morbidity, and below-knee amputation. There is currently a need for sustained compression across fusion sites using a TTC hindfoot nail with good mechanical stability. The DynaNail TTC Fusion System (MedShape, Inc, Atlanta, GA) uses an internal nitinol compression element to apply sustained compression across the tibiotalar and subtalar joints after surgery. In preliminary clinical cases, we have found that the nail is safe, reliable, and has promising clinical and radiographic results in settings of hindfoot arthritis, complex deformity, Charcot arthropathy, and talar avascular necrosis. LEVELS OF EVIDENCE: Expert opinion, Level V. PMID- 26264638 TI - Citrullination in the periodontium--a possible link between periodontitis and rheumatoid arthritis. AB - OBJECTIVES: The aim of the present study was to assess human and bacterial peptidylarginine deiminase (PAD) activity in the gingival crevicular fluid (GCF) in the context of serum levels of antibodies against citrullinated epitopes in rheumatoid arthritis and periodontitis. MATERIALS AND METHODS: Human PAD and Porphyromonas gingivalis-derived enzyme (PPAD) activities were measured in the GCF of 52 rheumatoid arthritis (RA) patients (48 with periodontitis and 4 without) and 44 non-RA controls (28 with periodontitis and 16 without). Serum antibodies against citrullinated epitopes were measured by ELISA. Bacteria being associated with periodontitis were determined by nucleic-acid-based methods. RESULTS: Citrullination was present in 26 (50%) RA patients and 23 (48%) controls. PAD and PPAD activities were detected in 36 (69%) and 30 (58%) RA patients, respectively, and in 30 (68%) and 21 (50%) controls, respectively. PPAD activity was higher in RA and non-RA patients with periodontitis than in those without (p = 0.038; p = 0.004), and was detected in 35 of 59 P. gingivalis positive samples, and in 16 of 37 P. gingivalis-negative samples in association with high antibody levels against that species. CONCLUSIONS: PAD and PPAD activities within the periodontium are elevated in RA and non-RA patients with periodontitis. PPAD secreted by P. gingivalis residing in epithelial cells may exert its citrullinating activity in distant regions of the periodontium or even distant tissues. CLINICAL RELEVANCE: In periodontitis, the citrullination of proteins/peptides by human and bacterial peptidylarginine deiminases may generate antibodies after breaching immunotolerance in susceptible individuals. PMID- 26264639 TI - Loss of cytokeratin 10 indicates malignant transformation in actinic cheilitis. AB - OBJECTIVES: The aim of this study was to investigate the relationship the expression of cytokeratins (CK10 and CK13) and the cell proliferation index determined by Ki-67 of lip squamous cell carcinoma and actinic cheilitis with different degrees of dysplasia. MATERIALS AND METHODS: Forty-five paraffin embedded actinic cheilitis with and without dysplasia and 20 lip squamous cell carcinoma were analyzed by immunohistochemistry using anti-human anti-CK10, anti CK13, and anti-Ki-67 antibodies. RESULTS: The majority of actinic cheilitis showed immunopositivity for CK10 and CK13 with decrease or loss of expression in dysplastic areas. In lip squamous cell carcinoma of the lip, heterogeneous expression of CK13 and immunonegativity for CK10 were observed. There was a statistically significant difference between CK10 expression in lip squamous cell carcinoma and in actinic cheilitis with or without dysplasia (p < 0.001). The cell proliferation index was higher in actinic cheilitis with dysplasia and lip squamous cell carcinoma than in actinic cheilitis without epithelial dysplasia. A significant correlation was found between the intensity of the epithelial dysplasia and the cell proliferation index (p < 0.001). CONCLUSION: These results provide evidence that there is a downregulation of CK10 expression in dysplastic areas of patients with actinic cheilitis and in those with lip squamous cell carcinoma (LSCC) and that the index of cell proliferation, determined by Ki-67, is directly correlated with the intensity of the epithelial dysplasia. CLINICAL RELEVANCE: Altogether, these results suggest that CK10 expression and the epithelial cell proliferation index can help to identify malignant transformation in the lip region. PMID- 26264640 TI - Cesarean Section Delivery Is Not a Risk Factor for Development of Inflammatory Bowel Disease: A Population-based Analysis. AB - BACKGROUND & AIMS: Mode of birth affects development of the intestinal microbiota, and microbial dysbiosis has been associated with inflammatory bowel disease (IBD). We performed a population-based analysis to determine whether mode of delivery (cesarean section vs. vaginal delivery) affects risk of IBD. METHODS: We collected data from the University of Manitoba IBD Epidemiology Database, which contains records on all Manitobans diagnosed with IBD from 1984 through 2010. Starting in 1970, 6-digit family health registration numbers were used in Manitoba to link mothers with their offspring. Maternal health records, including dates and modes of delivery and siblings of individuals with IBD, were identified. RESULTS: We obtained data on 1671 individuals with IBD and 10,488 controls (individuals without IBD, matched by age, sex, and area of residence at IBD diagnosis) linked to mothers' obstetrical records. Higher proportions of urban than rural residents were delivered by cesarean section for IBD cases (12.8% vs. 9.7%, P = .05) and controls (13.3% vs. 9.4%, P < .0001). A higher percentage of men with Crohn's disease than women with Crohn's disease were born via cesarean section (13.5% vs. 8.4%, P = .01). Overall, there was no difference in the percentage of IBD cases born by cesarean section (11.6%) vs. controls (11.7%, P = .93). In multivariate analysis, birth by cesarean section was not associated with an increased risk of subsequent IBD, controlling for age, sex, urban residence, and income (odds ratio, 1.04; 95% confidence interval, 0.89 1.23). Persons with IBD were no more likely to have been born by cesarean section than their siblings without IBD (1740 siblings from 1615 families) (11.6% vs. 11.3%; odds ratio, 1.14; 95% confidence interval, 0.72-1.80; P = .79). CONCLUSIONS: People with IBD were not more likely to have been born via cesarean section than controls or siblings without IBD. These findings indicate that events of the immediate postpartum period that shape the developing intestinal microbiome do not affect risk for IBD. PMID- 26264641 TI - Nitrogen-Doped Carbon Nanocoil Array Integrated on Carbon Nanofiber Paper for Supercapacitor Electrodes. AB - Integrating a nanostructured carbon array on a conductive substrate remains a challenging task that presently relies primarily on high-vacuum deposition technology. To overcome the problems associated with current vacuum techniques, we demonstrate the formation of an N-doped carbon array by pyrolysis of a polymer array that was electrochemically grown on carbon fiber paper. The resulting carbon array was investigated for use as a supercapacitor electrode. In-depth surface characterization results revealed that the microtextural properties, surface functionalities, and degree of nitrogen incorporated into the N-doped carbon array can be delicately controlled by manipulating carbonization temperatures. Furthermore, electrochemical measurements showed that subtle changes in these physical properties resulted in significant changes in the capacitive behavior of the N-doped carbon array. Pore structures and nitrogen/oxygen functional groups, which are favorable for charge storage, were formed at low carbonization temperatures. This result showed the importance of having a comprehensive understanding of how the surface characteristics of carbon affect its capacitive performance. When utilized as a substrate in a pseudocapacitive electrode material, the N-doped carbon array maximizes capacitive performance by simultaneously achieving high gravimetric and areal capacitances due to its large surface area and high electrical conductivity. PMID- 26264642 TI - The Development of Conversation Training Therapy: A Concept Paper. AB - OBJECTIVES: To introduce the conceptual, theoretical, and practical foundations of a novel approach to voice therapy, called conversation training therapy (CTT), which focuses exclusively on voice awareness and efficient voice production in patient-driven conversational narrative, without the use of a traditional therapeutic hierarchy. CTT is grounded in motor learning theory, focused on training target voice goals in spontaneous, conversational speech in the first session and throughout. CTT was developed by a consensus panel of expert clinical voice-specialized speech-language pathologists (SLPs) and patients with voice problems. STUDY DESIGN: This is a prospective, clinical consensus design. METHODS: A preliminary CTT approach to voice therapy was developed by the first and last authors (J.G-S. and A.I.G.) and incorporated six interchangeable tenets: clear speech, auditory/kinesthetic awareness, rapport building, negative practice, basic training gestures, and prosody. Five expert voice-specialized clinical SLPs (consensus group) were then presented CTT and a discussion ensued. Later, an informal interview by a neutral third party person occurred for further recommendations for CTT. RESULTS: The CTT approach was modified to reflect all the consensus groups' recommendations, which included the need for more detail and rationale in the program, troubleshooting suggestions, and the concern for potential challenges for novice clinicians. CONCLUSIONS: CTT is a new therapy approach based on motor learning theory, which exclusively uses patient-driven conversational narrative as the sole therapeutic stimuli. CTT is conceptually innovative because it represents an approach to voice therapy developed without the use of a traditional therapeutic hierarchy. It is also developed using input from patients with voice disorders and expert clinical providers. PMID- 26264643 TI - Bioinspired photonic structures by the reflector layer of firefly lantern for highly efficient chemiluminescence. AB - Fireflies have drawn considerable attention for thousands of years due to their highly efficient bioluminescence, which is important for fundamental research and photonic applications. However, there are few reports on the reflector layer (RL) of firefly lantern, which contributes to the bright luminescence. Here we presented the detailed microstructure of the RL consisting of random hollow granules, which had high reflectance in the range from 450 nm to 800 nm. Inspired by the firefly lantern, artificial films with high reflectance in the visible region were fabricated using hollow silica microparticles mimicking the structure of the RL. Additionally, the bioinspired structures provided an efficient RL for the chemiluminescence system and could substantially enhance the initial chemiluminescence intensity. The work not only provides new insight into the bright bioluminescence of fireflies, but also is importance for the design of photonic materials for theranostics, detection, and imaging. PMID- 26264644 TI - Specific photothermal therapy to the tumors with high EphB4 receptor expression. AB - Photothermal therapy (PTT) employs photo-absorbing agents to generate heat from optical energy, leading to the 'burning' of tumor cells. Real-time imaging of in vivo distribution of photothermal agents and monitoring of post-treatment therapeutic outcomes are very important to design and optimize personalized PTT treatment. In this work, we used chitosan-stearic acid copolymer (CSO-SA) to encapsulate hollow gold nanospheres (HAuNS) and near-infrared (NIR) fluorescent tracer, DiR. Then, the surface of nanoparticles was further conjugated with a peptide (TNYL), which facilitates EphB4-positive tumor targeting delivery. Using a paired tumor mode in vivo and a double tumor-cell co-culture strategy in vitro, we demonstrated the feasibility of increasing the accumulation of our nanoparticles (DiR loaded and TNYL-CSO-SA coated HAuNS (DTCSH)) into EphB4 positive tumors through interaction between TNYL-peptide on the nanoparticles and EpHB4 receptors on tumor cells. When combined with NIR laser irradiation, our nanoparticles induced more EphB4-positive tumor cells death in vitro. We further developed optical imaging to temporally and spatially monitor the biodistribution of DTCSH. Under NIR laser irradiation, PTT exhibited dramatically stronger antitumor effect against EphB4-positive tumors than EphB4-negative tumors. This was attributed to enhanced accumulation of our nanoparticles in EphB4-positive tumors. PMID- 26264645 TI - Development of tailored and self-mineralizing citric acid-crosslinked hydrogels for in situ bone regeneration. AB - Bone tissue engineering demands alternatives overcoming the limitations of traditional approaches in the context of a constantly aging global population. In the present study, elastin-like recombinamers hydrogels were produced by means of carbodiimide-catalyzed crosslinking with citric acid, a molecule suggested to be essential for bone nanostructure. By systematically studying the effect of the relative abundance of reactive species on gelation and hydrogel properties such as functional groups content, degradation and structure, we were able to understand and to control the crosslinking reaction to achieve hydrogels mimicking the fibrillary nature of the extracellular matrix. By studying the effect of polymer concentration on scaffold mechanical properties, we were able to produce hydrogels with a stiffness value of 36.13 +/- 10.72 kPa, previously suggested to be osteoinductive. Microstructured and mechanically-tailored hydrogels supported the growth of human mesenchymal stem cells and led to higher osteopontin expression in comparison to their non-tailored counterparts. Additionally, tailored hydrogels were able to rapidly self-mineralize in biomimetic conditions, evidencing that citric acid was successfully used both as a crosslinker and a bioactive molecule providing polymers with calcium phosphate nucleation capacity. PMID- 26264646 TI - Nanoparticle delivery of CDDO-Me remodels the tumor microenvironment and enhances vaccine therapy for melanoma. AB - Lipid-calcium-phosphate nanoparticle (NP) delivery of Trp2 peptide vaccine is one of the most effective vaccine strategies against melanoma. However, due to the immunosuppressive microenvironment in the tumor, the achievement of potent immune responses remains a major challenge. NP delivery systems provide an opportunity to deliver chemotherapy agent to modulate the tumor microenvironment (TME) and improve the vaccine activity. Anti-inflammatory triterpenoid methyl-2-cyano-3,12 dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) is a broad spectrum inhibitor of several signaling pathways that are important in both cancer cells and cells in the TME. Intravenous delivery of CDDO-Me using poly-lactic-glycolic-acid NP combination with subcutaneous Trp2 vaccine resulted in an increase of antitumor efficacy and apoptotic tumor tissue than Trp2 vaccine alone in B16F10 melanoma. There was a significant decrease of both Treg cells and MDSCs and a concomitant increase in the cytotoxic T-lymphocyte infiltration in TEM of the vaccinated animals. Also, CDDO-Me remodeled the tumor associated fibroblasts, collagen and vessel in TME, meanwhile, enhanced the Fas signaling pathway which could sensitize the tumor cells for cytotoxic T lymphocyte mediated killing. The combination of systemic induction of antigen-specific immune response using Trp2 nanovaccine and targeted modification of the TME with the NP delivered CDDO-Me offers a powerful combination therapy for melanoma. PMID- 26264647 TI - Visualizing myocardial inflammation in a rat model of type 4 cardiorenal syndrome by dual-modality molecular imaging. AB - Type 4 cardiorenal syndrome (CRS) is a life-threatening world health problem in which chronic kidney disease leads to progressive cardiovascular disease. In type 4 CRS, cardiac inflammation is an excellent target for both detection and therapy; however, this progression was underestimated by previous studies due to the lack of effective detection methods. To noninvasively visualize cardiac inflammation and monitor therapeutic efficacy of anti-inflammatory treatment in type 4 CRS, we here synthesized a dual-modality magneto-fluorescent nanoparticle (MNP) by combining ultrasmall superparamagnetic iron oxide nanoparticle and Rhodamine B for both magnetic resonance imaging (MRI) and optical imaging. This dual-functional MNP exhibited excellent performance such as high r2 relaxivity coefficient (283.4 mM(-1) s(-1)), high magnetism (96.7 emu/g iron) and a near neutral surface charge to minimize the reticuloendothelial system uptake. In vivo cardiac MRI showed significant negative contrast in the type 4 CRS rats, and the signal intensity on optical imaging was significantly higher in the type 4 CRS group compared with sham-operated and drug-treated groups. The specific targeting profile of MNPs to monocyte-macrophages was proven by histopathological analysis. Taken together, we demonstrate that this dual-modality strategy is feasible for noninvasively assessing myocardial inflammation and monitoring therapeutic efficacy in type 4 CRS. PMID- 26264649 TI - Acoustic suppression of the coffee-ring effect. AB - We study the influence of acoustic fields on the evaporative self-assembly of solute particles suspended inside sessile droplets of complex fluids. The self assembly process often results in an undesirable ring-like heterogeneous residue, a phenomenon known as the coffee-ring effect. Here we show that this ring-like self-assembly can be controlled acoustically to form homogeneous disc-like or concentrated spot-like residues. The principle of our method lies in the formation of dynamic patterns of particles in acoustically excited droplets, which inhibits the evaporation-driven convective transport of particles towards the contact line. We elucidate the mechanisms of this pattern formation and also obtain conditions for the suppression of the coffee-ring effect. Our results provide a more general solution to suppress the coffee-ring effect without any physiochemical modification of the fluids, the particles or the surface, thus potentially useful in a broad range of industrial and analytical applications that require homogenous solute depositions. PMID- 26264648 TI - Examination of early group dynamics and treatment outcome in a randomized controlled trial of group cognitive behavior therapy for binge eating disorder. AB - This study examined whether perceptions of group dynamics early in treatment predicted eating disorder outcomes in a sample of adults (N = 190) with binge eating disorder (BED) who participated in a 15-session group cognitive behavior therapy (gCBT) treatment with differing levels of therapist involvement (therapist led, therapist assisted, and self-help). The group dynamic variables included the Engaged subscale of the Group Climate Questionnaire--Short Form and the Group Attitude Scale, measured at session 2 and session 6. Treatment outcome was assessed in terms of global eating disorder severity and frequency of binge eating at end of treatment, 6-month, and 12-month follow-up. Session 2 engagement and group attitudes were associated with improved outcome at 12-month follow-up. No other group dynamic variables were significantly associated with treatment outcome. Group dynamic variables did not differ by levels of therapist involvement. Results indicate that early engagement and attitudes may be predictive of improved eating disorder psychopathology at 12 month follow-up. However, the pattern of mostly insignificant findings indicates that in gCBT, group process variables may be less influential on outcomes relative to other treatment components. Additionally, participants were able to engage in group treatment regardless of level of therapist involvement. PMID- 26264650 TI - Increased expression of transcription factor EB (TFEB) is associated with autophagy, migratory phenotype and poor prognosis in non-small cell lung cancer. AB - OBJECTIVES: We investigated the role of lysosomal biogenesis and hydrolase activity in the clinical behavior and postoperative outcome of lung cancer. MATERIALS AND METHODS: Using immunohistochemistry we investigated the expression of the transcription factor EB (TFEB) which orchestrates lysosomal biogenesis, the lysosome membrane protein LAMP2a and of the lysosomal hydrolase cathepsin D in a series of 98 non-small cell lung carcinomas (NSCLC) treated with surgery alone. In vitro experiments with the A549 and H1299 lung cancer cell lines were also performed. RESULTS: Overexpression of TFEB, LAMP2a and Cathepsin D was noted in 47/98 (47.9%), 43/98 (43.9%) and 39/98 (39.8%) cases, respectively, and were significantly correlated with each other and with adenocarcinomas. High LAMP2a was related to high histology grade. Linear regression analysis confirmed significant association of TFEB with BNIP3 (p=0.0003, r=0.35) and LC3A with LAMP2a expression (p=0.0002, r=0.37). An inverse association of Cathepsin D expression with stone-like structures (SLS) was recorded (p=0.02, r=0.22). On univariate analysis all three lyososomal variables were associated with poor prognosis (p=0.05, 0.04 and 0.01, for TFEB, Cathepsin D and LAMP2a, respectively). Multivariate analysis showed that the SLS number (p=0.0001, HR5.37), Cathepsin D expression (p=0.01, HR=2.2) and stage (p=0.01, HR=1.5) were independent prognostic variables. Silencing of TFEB with siRNAs in the A549 and H1299 lung cancer cell lines did not affect proliferation but resulted in reduced migration ability. CONCLUSION: Lysosomal biogenesis is linked to autophagosomal protein expression in NSCLC and characterizes subgroups of high risk patients after complete surgical lung tumor resection. PMID- 26264651 TI - Cold plasma treatment enhances oilseed rape seed germination under drought stress. AB - Effects of cold plasma treatment on seed germination, seedling growth, antioxidant enzymes, lipid peroxidation levels and osmotic-adjustment products of oilseed rape under drought stress were investigated in a drought-sensitive (Zhongshuang 7) and drought-tolerant cultivar (Zhongshuang 11). Results showed that, under drought stress, cold plasma treatment significantly improved the germination rate by 6.25% in Zhongshuang 7, and 4.44% in Zhongshuang 11. Seedling growth characteristics, including shoot and root dry weights, shoot and root lengths, and lateral root number, significantly increased after cold plasma treatment. The apparent contact angle was reduced by 30.38% in Zhongshuang 7 and 16.91% in Zhongshuang 11. Cold plasma treatment markedly raised superoxide dismutase and catalase activities by 17.71% and 16.52% in Zhongshuang 7, and by 13.00% and 13.21% in Zhongshuang 11. Moreover, cold plasma treatment significantly increased the soluble sugar and protein contents, but reduced the malondialdehyde content in seedlings. Our results suggested that cold plasma treatment improved oilseed rape drought tolerance by improving antioxidant enzyme activities, increasing osmotic-adjustment products, and reducing lipid peroxidation, especially in the drought-sensitive cultivar (Zhongshuang 7). Thus, cold plasma treatment can be used in an ameliorative way to improve germination and protect oilseed rape seedlings against damage caused by drought stress. PMID- 26264652 TI - Lack of the evidence for the enzymatic catabolism of Man1GlcNAc2 in Saccharomyces cerevisiae. AB - In the cytosol of Saccharomyces cerevisiae, most of the free N-glycans (FNGs) are generated from misfolded glycoproteins by the action of the cytoplasmic peptide: N-glycanase (Png1). A cytosol/vacuole alpha-mannosidase, Ams1, then trims the FNGs to eventually form a trisaccharide composed of Manbeta1,4GlcNAc beta1,4GlcNAc (Man1GlcNAc2). Whether or not the resulting Man1GlcNAc2 is enzymatically degraded further, however, is currently unknown. The objective of this study was to unveil the fate of Man1GlcNAc2 in S. cerevisiae. Quantitative analyses of the FNGs revealed a steady increase in the amount of Man1GlcNAc2 produced in the post-diauxic and stationary phases, suggesting that this trisaccharide is not catabolized during this period. Inoculation of the stationary phase cells into fresh medium resulted in a reduction in the levels of Man1GlcNAc2. However, this reduction was caused by its dilution due to cell division in the fresh medium. Our results thus indicate that Man1GlcNAc2 is not enzymatically catabolized in S. cerevisiae. PMID- 26264653 TI - Patient-reported outcome after treatment of urinary incontinence in a multidisciplinary pelvic care clinic. AB - OBJECTIVES: To assess patient-reported outcome and satisfaction regarding urinary incontinence 1 year after the end of treatment in a multidisciplinary pelvic care clinic. METHODS: A total of 647 patients with urinary incontinence seen in an academic multidisciplinary pelvic care clinic were prospectively included in a specific triage system. Patient-reported improvement of urinary incontinence and patient satisfaction were assessed by telephone survey 1 year after the end of treatment. RESULTS: Just 15.6% of patients presented with one single pelvic floor problem, most had two or three pelvic functional disorders simultaneously, such as urinary incontinence, pelvic organ prolapse and constipation or fecal incontinence. One year after the end of treatment, of 440 responders (68%), 18.2% reported no remaining complaints, and 33.4% reported only one complaint. Patients reported a significant improvement of the mean severity (scale 0-10) of urinary incontinence from 7.2 +/-1.6 pretreatment (=T0) to 4.3 +/- 3.0 1 year after the end of treatment (P < 0.001). A total of 20.6% of patients reported no urinary incontinence after 1 year (P < 0.001), and 27.6% (P < 0.001) stopped using incontinence pads. Patients claimed high satisfaction with the clinic and care received, with 35.8% being "satisfied" and 45.5% "very satisfied." CONCLUSION: At 1 year after the end of treatment, one out of five patients with urinary incontinence recovered completely, and more than one out of four stopped using incontinence absorption pads. One out of three patients went from having a multifactorial health problem to a monofactorial health problem. High satisfaction rates were reported by more than four out of five patients. PMID- 26264654 TI - miR-544a induces epithelial-mesenchymal transition through the activation of WNT signaling pathway in gastric cancer. AB - The epithelial-mesenchymal transition (EMT) contributes to cancer progression, as well as the development of normal organs, wound healing and organ fibrosis. We established a cell-based reporter system for identifying EMT-inducing microRNAs (miRNAs) with a gastric cancer (GC) cell line, MKN1, transfected with a reporter construct containing a promoter sequence of VIM in the 5' upstream region of the TurboRFP reporter gene. Function-based screening using this reporter system was performed with a 328-miRNA library, and resulted in the identification miR-544a as an EMT-inducing miRNA. Although miR-544a is already known to be involved in the regulation of CDH1, the mechanism by which EMT occurs remains poorly understood. Herein, we demonstrated that overexpression of miR-544a induces VIM, SNAI1 and ZEB1 expression, and reduces CDH1 expression, resulting in an EMT phenotype. In addition, we found that CDH1 and AXIN2, which are related to the degradation and the translocation of beta-catenin, are direct targets of miR 544a. Subsequently, the reduction of CDH1 and AXIN2 by miR-544a induced the nuclear import of beta-catenin, suggesting that miR-544a may activate the WNT signaling pathway through the stabilization of beta-catenin in nucleus. Our findings raise the possibility that inhibition of miR-544a may be a therapeutic target of metastatic GC. PMID- 26264655 TI - A remarkable enhancement of selectivity towards versatile analytes by a strategically integrated H-bonding site containing phase. AB - A double beta-alanylated L-glutamide-derived organic phase has been newly designed and synthesized in such a way that integrated H-bonding (interaction) sites make it very suitable for the separation of versatile analytes, including shape-constrained isomers, and nonpolar, polar and basic compounds. The beta alanine residues introduced into two long-chain alkyl group moieties provide ordered polar groups through H-bonding among the amide groups. PMID- 26264656 TI - High thermoelectric performance in two-dimensional graphyne sheets predicted by first-principles calculations. AB - The thermoelectric properties of two-dimensional graphyne sheets are investigated by using first-principles calculations and the Boltzmann transport equation method. The electronic structure indicates a semiconducting phase for graphyne, compared with the metallic phase of graphene. Consequently, the obtained Seebeck coefficient and the power factor of graphyne are much higher than those of graphene. The calculated phonon mean free path for graphene is 866 nm, which is in good agreement with the experimental value of 775 nm. Meanwhile the phonon mean free path of graphyne is only 60 nm, leading to two order lower thermal conductivity than graphene. We show that the low thermal conductivity of graphyne is due to its mixed sp/sp(2) bonding. Our calculations show that the optimized ZT values of graphyne sheets can reach 5.3 at intermediate temperature by appropriate doping. PMID- 26264659 TI - In vitro antibiofilm activity of the freshwater bryozoan Hyalinella punctata: a case study of Pseudomonas aeruginosa PAO1. AB - The antibiofilm and possible antiquorum sensing effects against the strain Pseudomonas aeruginosa PAO1 of five crude extracts of the freshwater bryozoan Hyalinella punctata (Hancock, 1850) were evaluated in vitro for the first time. H. punctata ethyl acetate extract (HpEtAc) exhibited the highest antibiofilm activity reducing the biofilm formation of P. aeruginosa PAO1 in the range of 80.63-88.13%. While all tested extracts reduced the twitching motility of the aforementioned bacterial strain, HpEtAc showed to be the most effective. Finally, at a concentration of 0.5 MIC, the same extract mostly inhibited the production of pyocyanin by P. aeruginosa PAO1 (71.53%). In comparison both with the positive controls used (streptomycin and ampicillin, 67.13 and 69.77%, respectively), HpEtAc was found to inhibit pyocyanin in a higher extent. An extensive chemical characterisation of this particular extract may result in isolation and identification of novel lead compounds targeting P. aeruginosa, an opportunistic human pathogen. PMID- 26264660 TI - NMR study on the interaction of the conserved CREX 'stem-loop' in the Hepatitis E virus genome with a naphthyridine-based ligand. AB - A 2-amino-1,8-naphthyridine derivative that is described to bind single guanine bulges in RNA-DNA and RNA-RNA duplexes was synthesized and its interaction with the single G bulge in the conserved CREX of the Hepatitis E Virus (HEV) genome was explored by NMR and molecular modeling. Results indicate that the ligand intercalates in the internal loop, though none of the expected hydrogen bonds with the single G in the bulge could be demonstrated. PMID- 26264658 TI - MRI detection of breast cancer micrometastases with a fibronectin-targeting contrast agent. AB - Metastasis is the primary cause of death in breast cancer patients. Early detection of high-risk breast cancer, including micrometastasis, is critical in tailoring appropriate and effective interventional therapies. Increased fibronectin expression, a hallmark of epithelial-to-mesenchymal transition, is associated with high-risk breast cancer and metastasis. We have previously developed a penta-peptide CREKA (Cys-Arg-Glu-Lys-Ala)-targeted gadolinium-based magnetic resonance imaging (MRI) contrast agent, CREKA-Tris(Gd-DOTA)3 (Gd-DOTA (4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecyl gadolinium), which binds to fibrin-fibronectin complexes that are abundant in the tumour microenvironment of fast-growing breast cancer. Here we assess the capability of CREKA-Tris(Gd-DOTA)3 to detect micrometastasis with MRI in co-registration with high-resolution fluorescence cryo-imaging in female mice bearing metastatic 4T1 breast tumours. We find that CREKA-Tris(Gd-DOTA)3 provides robust contrast enhancement in the metastatic tumours and enables the detection of micrometastases of size <0.5 mm, extending the detection limit of the current clinical imaging modalities. These results demonstrate that molecular MRI with CREKA-Tris(Gd-DOTA)3 may facilitate early detection of high-risk breast cancer and micrometastasis in the clinic. PMID- 26264661 TI - Assessment of successful smoking cessation by psychological factors using the Bayesian network approach. AB - The association between psychological factors and smoking cessation is complicated and inconsistent in published researches, and the joint effect of psychological factors on smoking cessation is unclear. This study explored how psychological factors jointly affect the success of smoking cessation using a Bayesian network approach. A community-based case control study was designed with 642 adult male successful smoking quitters as the cases, and 700 adult male failed smoking quitters as the controls. General self-efficacy (GSE), trait coping style (positive-trait coping style (PTCS) and negative-trait coping style (NTCS)) and self-rating anxiety (SA) were evaluated by GSE Scale, Trait Coping Style Questionnaire and SA Scale, respectively. Bayesian network was applied to evaluate the relationship between psychological factors and successful smoking cessation. The local conditional probability table of smoking cessation indicated that different joint conditions of psychological factors led to different outcomes for smoking cessation. Among smokers with high PTCS, high NTCS and low SA, only 36.40% successfully quitted smoking. However, among smokers with low pack-years of smoking, high GSE, high PTCS and high SA, 63.64% successfully quitted smoking. Our study indicates psychological factors jointly influence smoking cessation outcome. According to different joint situations, different solutions should be developed to control tobacco in practical intervention. PMID- 26264662 TI - Peritumoral D2-40 Chalkley score independently predicts metastases and survival in patients with cutaneous malignant melanoma. AB - BACKGROUND: Many observational studies investigated the prognostic significance of angiogenesis and lymphangiogenesis in patients with melanoma. However, the obtained results are rather contradictory, probably due to the lack of the consensus methodology. METHODS: To investigate the prognostic significance of angiogenesis and lymphangiogenesis-related parameters in patients with melanoma, we performed a retrospective investigation following the consensus recommendations for angiogenesis and lymphangiogenesis quantification in solid tumors and reporting recommendations for tumor marker (REMARK) criteria for reporting the results. Blood and lymphatic vessel Chalkley scores, endothelial cell proliferation fractions and microvessel densities were quantified using a double immunostaining for endothelial marker CD34 or lymphendothelial marker D240 and the proliferation marker Ki-67 in 196 patients with melanoma. These parameters were evaluated separately for peritumoral (PT) and intratumoral areas and were correlated with outcome. RESULTS: In multivariate analysis PT D240 Chalkley score was identified as a strongest predictor for sentinel lymph node metastases, non-sentinel lymph node metastases, distant metastases, disease free survival and overall survival in patients with melanoma. CONCLUSIONS: If additional studies corroborate our findings, we believe that the inclusion of PT D240 Chalkley counts to the routine pathology examination of melanoma samples would provide additional information for identifying high-risk patients. PMID- 26264663 TI - The impact of the phosphomimetic eIF2alphaS/D on global translation, reinitiation and the integrated stress response is attenuated in N2a cells. AB - A plethora of stresses trigger a rapid downregulation of protein synthesis. However, a fraction of mRNAs continue to be recruited onto polysomes and their protein products play a key role in deciding cell fate. These transcripts are characterized by the presence of uORFs within their 5' TL coupling protein expression to reinitiation. The translational brake arises due to the activation of a family of kinases targeting the alpha subunit of the trimolecular eIF2(alphabetagamma) initiation factor. Phosphorylation of eIF2alphaSer51 inhibits ternary complex regeneration reducing the pool of 43S ribosomes. It is popular to mimic this event, and hence the integrated stress response (ISR), by the expression of the phosphomimetic eIF2alphaS51D. However, we report that whereas the ISR is reproduced by eIF2alphaS51D expression in human HEK293T cells this is not the case in N2a mouse neuroblastoma cells. With regards to translational downregulation, this arises due to the failure of the phosphomimetic protein to assemble an eIF2 complex with endogenous eIF2beta/gamma. This can be compensated for by the transient co-expression of all three subunits. Curiously, these conditions do not modulate reinitiation and consequently fail to trigger the ISR. This is the first demonstration that the inhibitory and reinitiation functions of eIF2alphaS/D can be separated. PMID- 26264664 TI - Structural basis for selective targeting of leishmanial ribosomes: aminoglycoside derivatives as promising therapeutics. AB - Leishmaniasis comprises an array of diseases caused by pathogenic species of Leishmania, resulting in a spectrum of mild to life-threatening pathologies. Currently available therapies for leishmaniasis include a limited selection of drugs. This coupled with the rather fast emergence of parasite resistance, presents a dire public health concern. Paromomycin (PAR), a broad-spectrum aminoglycoside antibiotic, has been shown in recent years to be highly efficient in treating visceral leishmaniasis (VL)-the life-threatening form of the disease. While much focus has been given to exploration of PAR activities in bacteria, its mechanism of action in Leishmania has received relatively little scrutiny and has yet to be fully deciphered. In the present study we present an X-ray structure of PAR bound to rRNA model mimicking its leishmanial binding target, the ribosomal A site. We also evaluate PAR inhibitory actions on leishmanial growth and ribosome function, as well as effects on auditory sensory cells, by comparing several structurally related natural and synthetic aminoglycoside derivatives. The results provide insights into the structural elements important for aminoglycoside inhibitory activities and selectivity for leishmanial cytosolic ribosomes, highlighting a novel synthetic derivative, compound 3: , as a prospective therapeutic candidate for the treatment of VL. PMID- 26264665 TI - Structure and primase-mediated activation of a bacterial dodecameric replicative helicase. AB - Replicative helicases are essential ATPases that unwind DNA to initiate chromosomal replication. While bacterial replicative DnaB helicases are hexameric, Helicobacter pylori DnaB (HpDnaB) was found to form double hexamers, similar to some archaeal and eukaryotic replicative helicases. Here we present a structural and functional analysis of HpDnaB protein during primosome formation. The crystal structure of the HpDnaB at 6.7 A resolution reveals a dodecameric organization consisting of two hexamers assembled via their N-terminal rings in a stack-twisted mode. Using fluorescence anisotropy we show that HpDnaB dodecamer interacts with single-stranded DNA in the presence of ATP but has a low DNA unwinding activity. Multi-angle light scattering and small angle X-ray scattering demonstrate that interaction with the DnaG primase helicase-binding domain dissociates the helicase dodecamer into single ringed primosomes. Functional assays on the proteins and associated complexes indicate that these single ringed primosomes are the most active form of the helicase for ATP hydrolysis, DNA binding and unwinding. These findings shed light onto an activation mechanism of HpDnaB by the primase that might be relevant in other bacteria and possibly other organisms exploiting dodecameric helicases for DNA replication. PMID- 26264666 TI - DNA binding fluorescent proteins for the direct visualization of large DNA molecules. AB - Fluorescent proteins that also bind DNA molecules are useful reagents for a broad range of biological applications because they can be optically localized and tracked within cells, or provide versatile labels for in vitro experiments. We report a novel design for a fluorescent, DNA-binding protein (FP-DBP) that completely 'paints' entire DNA molecules, whereby sequence-independent DNA binding is accomplished by linking a fluorescent protein to two small peptides (KWKWKKA) using lysine for binding to the DNA phosphates, and tryptophan for intercalating between DNA bases. Importantly, this ubiquitous binding motif enables fluorescent proteins (Kd = 14.7 MUM) to confluently stain DNA molecules and such binding is reversible via pH shifts. These proteins offer useful robust advantages for single DNA molecule studies: lack of fluorophore mediated photocleavage and staining that does not perturb polymer contour lengths. Accordingly, we demonstrate confluent staining of naked DNA molecules presented within microfluidic devices, or localized within live bacterial cells. PMID- 26264667 TI - ROTS: reproducible RNA-seq biomarker detector-prognostic markers for clear cell renal cell cancer. AB - Recent comprehensive assessments of RNA-seq technology support its utility in quantifying gene expression in various samples. The next step of rigorously quantifying differences between sample groups, however, still lacks well-defined best practices. Although a number of advanced statistical methods have been developed, several studies demonstrate that their performance depends strongly on the data under analysis, which compromises practical utility in real biomedical studies. As a solution, we propose to use a data-adaptive procedure that selects an optimal statistic capable of maximizing reproducibility of detections. After demonstrating its improved sensitivity and specificity in a controlled spike-in study, the utility of the procedure is confirmed in a real biomedical study by identifying prognostic markers for clear cell renal cell carcinoma (ccRCC). In addition to identifying several genes previously associated with ccRCC prognosis, several potential new biomarkers among genes regulating cell growth, metabolism and solute transport were detected. PMID- 26264668 TI - Quantification of DNA cleavage specificity in Hi-C experiments. AB - Hi-C experiments produce large numbers of DNA sequence read pairs that are typically analyzed to deduce genomewide interactions between arbitrary loci. A key step in these experiments is the cleavage of cross-linked chromatin with a restriction endonuclease. Although this cleavage should happen specifically at the enzyme's recognition sequence, an unknown proportion of cleavage events may involve other sequences, owing to the enzyme's star activity or to random DNA breakage. A quantitative estimation of these non-specific cleavages may enable simulating realistic Hi-C read pairs for validation of downstream analyses, monitoring the reproducibility of experimental conditions and investigating biophysical properties that correlate with DNA cleavage patterns. Here we describe a computational method for analyzing Hi-C read pairs to estimate the fractions of cleavages at different possible targets. The method relies on expressing an observed local target distribution downstream of aligned reads as a linear combination of known conditional local target distributions. We validated this method using Hi-C read pairs obtained by computer simulation. Application of the method to experimental Hi-C datasets from murine cells revealed interesting similarities and differences in patterns of cleavage across the various experiments considered. PMID- 26264670 TI - New perspective on the haplosporidian parasites of molluscs. AB - The protist phylum Haplosporidia comprises over 40 described species with representatives infecting a range of mollusc hosts, including several ecologically and economically significant pathogens. Continuing exploration of haplosporidian diversity has added ten new species in recent years and brought the phylogenetics of the group into somewhat clearer focus, with monophyletic Bonamia and Minchinia lineages continuing to be supported. However, the addition of new sequences to phylogenetic analyses has left the paraphyletic genus Haplosporidium's picture less resolved. It is not clear that even two genera will be enough to accommodate the species presently drawn to the Haplosporidium regions of the haplosporidian tree. In this review, we summarize recent findings in haplosporidian diversity and phylogenetics, and provide a synthesis of our understanding of the life cycles and environmental influences on haplosporidians, with particular emphasis on the important pathogens Haplosporidium nelsoni and Bonamia ostreae. Additionally, we consider the evolution of the "microcell haplosporidian" lifestyle of Bonamia parasites, and suggest that colonization of high-density oyster host populations in relatively stable euhaline marine environments may have been an important development favoring the evolution of the microcell haplosporidian life strategy. PMID- 26264669 TI - Identification of large-scale genomic variation in cancer genomes using in silico reference models. AB - Identifying large-scale structural variation in cancer genomes continues to be a challenge to researchers. Current methods rely on genome alignments based on a reference that can be a poor fit to highly variant and complex tumor genomes. To address this challenge we developed a method that uses available breakpoint information to generate models of structural variations. We use these models as references to align previously unmapped and discordant reads from a genome. By using these models to align unmapped reads, we show that our method can help to identify large-scale variations that have been previously missed. PMID- 26264671 TI - Pathogenicity of Isaria fumosorosea to Bemisia tabaci, with some observations on the fungal infection process and host immune response. AB - Isaria fumosorosea is an important pathogen of whiteflies, and is used as a mycoinsecticide against this pest in many regions of the world. We quantified the pathogenicity of the Chinese isolate IF-1106 against different life stages of sweetpotato whitefly, Bemisia tabaci, on cucumber plants, and describe the infection process and aspects of the host immunological response in the laboratory. The second instar was the most susceptible life stage to infection, with mortality rates at 10(7)conidia/ml ~83% after 7d. Scanning electron microscopy was used to monitor morphological aspects of the infection process. The following stages were observed; conidia adhered on the cuticle of B. tabaci and began to germinate within 6h of inoculation, appressoria development after 24h, germ tube penetration within 48h, emergent hyphae within 72h, secondary conidiogenesis within 96h with mass hyphal proliferation occurring on cadavers within 120h. The activities of endogenous enzymes were evaluated from host homogenate at various intervals post infection. Three enzymes associated with antioxidant activity [superoxide dismutase (SOD), perioxidase (POD), and catalase (CAT)], and two with detoxification [glutathione S-transferase (GSTs) and carboxylesterase (CarE)] were apparently upregulated in second instars infected by I. fumosorosea. Enzyme activities reached peak values at 48-60h post infection, then decreased to significantly lower than controls in 84h as mycosis occurred. Our results provide new insights into the pathogenicity and potential physiological response of B. tabaci to this fungal isolate. PMID- 26264672 TI - Transracial adoptees bridging heritage and national cultures: Parental socialisation, ethnic identity and self-esteem. AB - Transracial adoptees represent a specific group of immigrants who experience unique immigration processes that bring them face-to-face with two cultural backgrounds: that of their heritage culture on one hand and that of their national culture on the other hand. However, there is a scarcity of studies focused on the way these processes unfold within adoptive families. This study was aimed at exploring how transracial adoptees cope with the construction of their ethnic identity. Administering a self-report questionnaire to 127 transracial adoptees and their mothers, for a total of 254 participants, we first investigated the association between mothers' cultural socialisation (enculturation and preparation for bias strategies) and adoptees' ethnic identity (i.e. ethnic identity exploration and ethnic identity affirmation dimensions). We then investigated whether ethnic identity affects self-esteem by testing the hypothesis that national identity moderates the relationship between ethnic identity and self-esteem. Results revealed that mothers' enculturation (but not their preparation for bias) supported adoptees' ethnic identity exploration, which in turn was positively associated with ethnic identity affirmation. Moreover, we confirmed the moderation effect: ethnic identity affirmation enhanced the level of self-esteem, but only for those adoptees who perceived a higher degree of national identity affirmation. PMID- 26264675 TI - Mental health among UK inner city non-heterosexuals: the role of risk factors, protective factors and place. AB - BACKGROUND: Sexual minorities experience excess psychological ill health globally, yet the UK data exploring reasons for poor mental health among sexual minorities is lacking. This study compares the prevalence of a measure of well being, symptoms of common mental disorder (CMD), lifetime suicidal ideation, harmful alcohol and drug use among inner city non-heterosexual and heterosexual individuals. It is the first UK study which aims to quantify how much major, everyday and anticipated discrimination; lifetime and childhood trauma; and coping strategies for dealing with unfair treatment, predict excess mental ill health among non-heterosexuals. Further, inner city and national outcomes are compared. METHODS: Self-report survey data came from the South East London Community Health study (N = 1052) and the Adult Psychiatric Morbidity Survey (N = 7403). RESULTS: Adjustments for greater exposure to measured experiences of discrimination and lifetime and childhood trauma had a small to moderate impact on effect sizes for adverse health outcomes though in fully adjusted models, non heterosexual orientation remained strongly associated with CMD, lifetime suicidal ideation, harmful alcohol and drug use. There was limited support for the hypothesis that measured coping strategies might mediate some of these associations. The inner city sample had poorer mental health overall compared with the national sample and the discrepancy was larger for non-heterosexuals than heterosexuals. CONCLUSIONS: Childhood and adult adversity substantially influence but do not account for sexual orientation-related mental health disparities. Longitudinal work taking a life course approach with more specific measures of discrimination and coping is required to further understand these associations. Sexual minorities should be considered as a priority in the design and delivery of health and social services. PMID- 26264673 TI - Is the intention-behaviour gap greater amongst the more deprived? A meta-analysis of five studies on physical activity, diet, and medication adherence in smoking cessation. AB - OBJECTIVES: Unhealthy behaviour is more common amongst the deprived, thereby contributing to health inequalities. The evidence that the gap between intention and behaviour is greater amongst the more deprived is limited and inconsistent. We tested this hypothesis using objective and self-report measures of three behaviours, both individual- and area-level indices of socio-economic status, and pooling data from five studies. DESIGN: Secondary data analysis. METHODS: Multiple linear regressions and meta-analyses of data on physical activity, diet, and medication adherence in smoking cessation from 2,511 participants. RESULTS: Across five studies, we found no evidence for an interaction between deprivation and intention in predicting objective or self-report measures of behaviour. Using objectively measured behaviour and area-level deprivation, meta-analyses suggested that the gap between self-efficacy and behaviour was greater amongst the more deprived (B = .17 [95% CI = 0.02, 0.31]). CONCLUSIONS: We find no compelling evidence to support the hypothesis that the intention-behaviour gap is greater amongst the more deprived. STATEMENT OF CONTRIBUTION: What is already known on this subject? Unhealthy behaviour is more common in those who are more deprived. This may reflect a larger gap between intentions and behaviour amongst the more deprived. The limited evidence to date testing this hypothesis is mixed. What does this study add? In the most robust study to date, combining results from five trials, we found no evidence for this explanation. The gap between intentions and behaviour did not vary with deprivation for the following: diet, physical activity, or medication adherence in smoking cessation. We did, however, find a larger gap between perceived control over behaviour (self-efficacy) and behaviour in those more deprived. These findings add to existing evidence to suggest that higher rates of unhealthier behaviour in more deprived groups may be reduced by the following: ? Strengthening behavioural control mechanisms (such as executive function and non-conscious processes) or ? Behaviour change interventions that bypass behavioural control mechanisms. PMID- 26264676 TI - Paraneoplastic acanthosis nigricans: the first reported case associated with Sezary syndrome. PMID- 26264674 TI - Pretransplant platelet transfusion refractoriness is not associated with platelet nonengraftment in T-replete hematopoietic progenitor cell transplantation for hematologic malignancies. AB - BACKGROUND: Cellular engraftment after allogeneic hematopoietic progenitor cell transplantation (HPCT) can be affected by pre-HPCT antibodies against donor human leukocyte antigen (HLA; donor-specific antibodies [DSAs]), which are commonly acquired by either pregnancy or transfusion. Issues regarding high assay sensitivity and variable interpretation limit routine screening for DSAs. Platelet (PLT) transfusion refractoriness (PTR) is relatively common in patients with hematologic malignancies, and anti-HLA alloantibodies can be identified in up to 20% of cases. For patients with PTR undergoing subsequent allogeneic HPCT, however, the effect if any on subsequent PLT nonengraftment is unknown. STUDY DESIGN AND METHODS: We conducted a retrospective study of 480 adults who underwent T-replete HPCT for hematologic malignancy and compared the posttransplantation clinical outcomes between patients who were PTR before HPCT and those who were not. RESULTS: Multivariate analysis demonstrated that PTR was not directly associated with PLT nonengraftment or graft failure, but did predict for early intensive care unit admission, which was the only variable associated with these outcomes (p < 0.0001). CONCLUSION: Our findings suggest that PTR before HPCT identifies patients at higher risk of early clinical rather than immunologic complications. PMID- 26264677 TI - Evidence for fumonisin inhibition of ceramide synthase in humans consuming maize based foods and living in high exposure communities in Guatemala. AB - SCOPE: Fumonisin (FB) occurs in maize and is an inhibitor of ceramide synthase (CerS). We determined the urinary FB1 (UFB1 ) and sphingoid base 1-phosphate levels in blood from women consuming maize in high and low FB exposure communities in Guatemala. METHODS AND RESULTS: FB1 intake was estimated using the UFB1 . Sphinganine 1-phosphate (Sa 1-P), sphingosine 1-phosphate (So 1-P), and the Sa 1-P/So 1-P ratio were determined in blood spots collected on absorbent paper at the same time as urine collection. In the first study, blood spots and urine were collected every 3 months (March 2011 to February 2012) from women living in low (Chimaltenango and Escuintla) and high (Jutiapa) FB exposure communities (1240 total recruits). The UFB1 , Sa 1-P/So 1-P ratio, and Sa 1-P/mL in blood spots were significantly higher in the high FB1 intake community compared to the low FB1 intake communities. The results were confirmed in a follow-up study (February 2013) involving 299 women living in low (Sacatepequez) and high (Santa Rosa and Chiquimula) FB exposure communities. CONCLUSIONS: High levels of FB1 intake are correlated with changes in Sa 1-P and the Sa 1-P/So 1-P ratio in human blood in a manner consistent with FB1 inhibition of CerS. PMID- 26264678 TI - Evaluation of an immunochromatographic test for feline AB system blood typing. AB - OBJECTIVE: To determine the accuracy of an immunochromatographic cartridge (IC) test for blood typing feline type A, B, and AB blood samples. DESIGN: Prospective observational study. SETTING: University teaching hospital. SAMPLES: Fifty-one nonanemic and 19 anemic feline blood samples. INTERVENTIONS: Samples were blood typed by both card agglutination (CA) and IC techniques. Discordant results were analyzed using a back-typing technique for the presence of alloantibodies. Repeatability and reproducibility of the IC method were evaluated. Accuracy of the IC method was determined for feline whole blood anticoagulated with EDTA and citrate phosphate dextrose adenine (CPDA1), for feline-packed RBCs with CPDA1 and saline adenine glucose-mannitol, and for autoagglutinated and hemolytic samples. Accuracy of IC testing was determined for feline blood after room temperature, 4 +/- 2, -20, and -80 degrees C storage following 24, 48, 72, and 96 hours, and after 1, 2, 3, and 4 weeks of storage. MEASUREMENTS AND MAIN RESULTS: In anemic and nonanemic samples the IC technique had a specificity, sensitivity, positive predictive value, and negative predictive value of 100% in detecting feline blood types A, B, and AB, outperforming a CA test. Results were repeatable and reproducible. Using IC it was possible to blood type samples anticoagulated with EDTA and CPDA1, packed RBC samples with CPDA1 and saline adenine glucose mannitol, autoagglutinated and hemolytic samples, and samples stored at 4 +/- 2 degrees C and at room temperature for up to 1 month. CONCLUSIONS: The IC technique is an accurate assay for the identification of A, B, and AB blood types in anemic and nonanemic feline blood. It has a higher sensitivity and specificity than the CA test, and can be used in samples stored with common anticoagulants or preservative solutions used in feline transfusion medicine. PMID- 26264679 TI - Introduction to the special issue on neural mechanisms of behavioral maturation. PMID- 26264680 TI - Research is needed on the difficult-to-cure population of hepatitis C virus patients with disability. PMID- 26264681 TI - Generation of high-value products by photosynthetic microorganisms: from sunlight to biofuels. Introduction. PMID- 26264683 TI - Functionalization of graphene using deep eutectic solvents. AB - Deep eutectic solvents (DESs) have received attention in various applications because of their distinctive properties. In this work, DESs were used as functionalizing agents for graphene due to their potential to introduce new functional groups and cause other surface modifications. Eighteen different types of ammonium- and phosphonium-salt-based DESs were prepared and characterized by FTIR. The graphene was characterized by FTIR, STA, Raman spectroscopy, XRD, SEM, and TEM. Additional experiments were performed to study the dispersion behavior of the functionalized graphene in different solvents. The DESs exhibited both reduction and functionalization effects on DES-treated graphene. Dispersion stability was investigated and then characterized by UV-vis spectroscopy and zeta potential. DES-modified graphene can be used in many applications, such as drug delivery, wastewater treatment, catalysts, composite materials, nanofluids, and biosensors. To the best of our knowledge, this is the first investigation on the use of DESs for graphene functionalization. PMID- 26264682 TI - A simplicial complex-based approach to unmixing tumor progression data. AB - BACKGROUND: Tumorigenesis is an evolutionary process by which tumor cells acquire mutations through successive diversification and differentiation. There is much interest in reconstructing this process of evolution due to its relevance to identifying drivers of mutation and predicting future prognosis and drug response. Efforts are challenged by high tumor heterogeneity, though, both within and among patients. In prior work, we showed that this heterogeneity could be turned into an advantage by computationally reconstructing models of cell populations mixed to different degrees in distinct tumors. Such mixed membership model approaches, however, are still limited in their ability to dissect more than a few well-conserved cell populations across a tumor data set. RESULTS: We present a method to improve on current mixed membership model approaches by better accounting for conserved progression pathways between subsets of cancers, which imply a structure to the data that has not previously been exploited. We extend our prior methods, which use an interpretation of the mixture problem as that of reconstructing simple geometric objects called simplices, to instead search for structured unions of simplices called simplicial complexes that one would expect to emerge from mixture processes describing branches along an evolutionary tree. We further improve on the prior work with a novel objective function to better identify mixtures corresponding to parsimonious evolutionary tree models. We demonstrate that this approach improves on our ability to accurately resolve mixtures on simulated data sets and demonstrate its practical applicability on a large RNASeq tumor data set. CONCLUSIONS: Better exploiting the expected geometric structure for mixed membership models produced from common evolutionary trees allows us to quickly and accurately reconstruct models of cell populations sampled from those trees. In the process, we hope to develop a better understanding of tumor evolution as well as other biological problems that involve interpreting genomic data gathered from heterogeneous populations of cells. PMID- 26264684 TI - Carbon Nanotube Flexible and Stretchable Electronics. AB - The low-cost and large-area manufacturing of flexible and stretchable electronics using printing processes could radically change people's perspectives on electronics and substantially expand the spectrum of potential applications. Examples range from personalized wearable electronics to large-area smart wallpapers and from interactive bio-inspired robots to implantable health/medical apparatus. Owing to its one-dimensional structure and superior electrical property, carbon nanotube is one of the most promising material platforms for flexible and stretchable electronics. Here in this paper, we review the recent progress in this field. Applications of single-wall carbon nanotube networks as channel semiconductor in flexible thin-film transistors and integrated circuits, as stretchable conductors in various sensors, and as channel material in stretchable transistors will be discussed. Lastly, state-of-the-art advancement on printing process, which is ideal for large-scale fabrication of flexible and stretchable electronics, will also be reviewed in detail. PMID- 26264685 TI - Carbon and Binder-Free Air Electrodes Composed of Co3O 4 Nanofibers for Li-Air Batteries with Enhanced Cyclic Performance. AB - In this study, to fabricate a carbon free (C-free) air electrode, Co3O4 nanofibers were grown directly on a Ni mesh to obtain Co3O4 with a high surface area and good contact with the current collector (the Ni mesh). In Li-air cells, any C present in the air electrode promotes unwanted side reactions. Therefore, the air electrode composed of only Co3O4 nanofibers (i.e., C-free) was expected to suppress these side reactions, such as the decomposition of the electrolyte and formation of Li2CO3, which would in turn enhance the cyclic performance of the cell. As predicted, the Co3O4-nanofiber electrode successfully reduced the accumulation of reaction products during cycling, which was achieved through the suppression of unwanted side reactions. In addition, the cyclic performance of the Li-air cell was superior to that of a standard electrode composed of carbonaceous material. PMID- 26264686 TI - Enhanced Photovoltaic Performance of Dye-Sensitized Solar Cells by Efficient Near Infrared Sunlight Harvesting using Upconverting Y2O 3:Er (3+)/Yb (3+) Phosphor Nanoparticles. AB - We report the efficiency enhancement in dye-sensitized solar cells (DSSCs) using Er(3+)/Yb(3+)-co-doped Y2O3 (i.e., Y2O3:Er(3+)/Yb(3+)) phosphor nanoparticles, prepared by a simple and cost-effective urea-based homogeneous precipitation method, for efficient near-infrared (NIR) sunlight harvesting. Under the light excitation at a wavelength of 980 nm, the as-prepared samples exhibited strong upconversion emissions at green and red visible wavelengths. To investigate the influence of Y2O3:Er(3+)/Yb(3+) nanoparticles on the photovoltaic performance of DSSCs, the phosphor nanoparticles were incorporated into titanium dioxide films to form a composite photoelectrode. For the resulting DSSCs, the increased power conversion efficiency (PCE) of 6.68 % was obtained mainly by the increased photocurrent of J SC = 13.68 mA/cm(2) due to the light harvesting enhancement via the NIR-to-visible upconversion process (cf., PCE = 5.94 %, J SC = 12.74 mA/cm(2) for the reference DSSCs without phosphor nanoparticles), thus, indicating the PCE increment ratio of ~12.4 %. PMID- 26264687 TI - Fabrication and Optimization of Vertically Aligned ZnO Nanorod Array-Based UV Photodetectors via Selective Hydrothermal Synthesis. AB - Vertically aligned ZnO nanorod array (NRA)-based ultraviolet (UV) photodetectors (PDs) were successfully fabricated and optimized via a facile hydrothermal process. Using a shadow mask technique, the thin ZnO seed layer was deposited between the patterned Au/Ti electrodes to bridge the electrodes. Thus, both the Au electrodes could be connected by the ZnO seed layer. As the sample was immersed into growth solution and heated at 90 degrees C, the ZnO NRAs were crystallized and vertically grown on the ZnO seed layer, thus creating a metal semiconductor-metal PD structure. To investigate the size effect of ZnO NRAs on photocurrent, the PDs were readily prepared with different concentrations of growth solution. For the ZnO NRAs grown at 25 mM of concentration, the PD with 10 MUm of channel width (i.e., gap distance between two electrodes) exhibited a high photocurrent of 1.91 * 10(-4) A at an applied bias of 10 V under 365 nm of UV light illumination. The PD was optimized by adjusting the channel width. For 15 MUm of channel width, a relatively high photocurrent on-off ratio of 37.4 and good current transient characteristics were observed at the same applied bias. These results are expected to be useful for cost-effective and practical UV PD applications. PMID- 26264688 TI - Effects of Energy Relaxation via Quantum Coupling Among Three-Dimensional Motion on the Tunneling Current of Graphene Field-Effect Transistors. AB - We report theoretical study of the effects of energy relaxation on the tunneling current through the oxide layer of a two-dimensional graphene field-effect transistor. In the channel, when three-dimensional electron thermal motion is considered in the Schrodinger equation, the gate leakage current at a given oxide field largely increases with the channel electric field, electron mobility, and energy relaxation time of electrons. Such an increase can be especially significant when the channel electric field is larger than 1 kV/cm. Numerical calculations show that the relative increment of the tunneling current through the gate oxide will decrease with increasing the thickness of oxide layer when the oxide is a few nanometers thick. This highlights that energy relaxation effect needs to be considered in modeling graphene transistors. PMID- 26264689 TI - Dietary carbohydrate and control of hepatic gene expression: mechanistic links from ATP and phosphate ester homeostasis to the carbohydrate-response element binding protein. AB - Type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) are associated with elevated hepatic glucose production and fatty acid synthesis (de novo lipogenesis (DNL)). High carbohydrate diets also increase hepatic glucose production and lipogenesis. The carbohydrate-response element-binding protein (ChREBP, encoded by MLXIPL) is a transcription factor with a major role in the hepatic response to excess dietary carbohydrate. Because its target genes include pyruvate kinase (PKLR) and enzymes of lipogenesis, it is regarded as a key regulator for conversion of dietary carbohydrate to lipid for energy storage. An alternative hypothesis for ChREBP function is to maintain hepatic ATP homeostasis by restraining the elevation of phosphate ester intermediates in response to elevated glucose. This is supported by the following evidence: (i) A key stimulus for ChREBP activation and induction of its target genes is elevation of phosphate esters; (ii) target genes of ChREBP include key negative regulators of the hexose phosphate ester pool (GCKR, G6PC, SLC37A4) and triose phosphate pool (PKLR); (iii) ChREBP knock-down models have elevated hepatic hexose phosphates and triose phosphates and compromised ATP phosphorylation potential; (iv) gene defects in G6PC and SLC37A4 and common variants of MLXIPL, GCKR and PKLR in man are associated with elevated hepatic uric acid production (a marker of ATP depletion) or raised plasma uric acid levels. It is proposed that compromised hepatic phosphate homeostasis is a contributing factor to the elevated hepatic glucose production and lipogenesis that associate with type 2 diabetes, NAFLD and excess carbohydrate in the diet. PMID- 26264690 TI - RE: Breast Cancer Risk After Salpingo-Oophorectomy in Healthy BRCA1/2 Mutation Carriers: Revisiting the Evidence for Risk Reduction. PMID- 26264691 TI - Response. PMID- 26264692 TI - Cytotoxic effects of high concentrations of sodium ascorbate on human myeloid cell lines. AB - The effect of high doses of intravenous (sodium) ascorbate (ASC) in the treatment of cancer has been controversial although there is growing evidence that ASC in high (pharmacologic) concentrations induces dose-dependent pro-apoptotic death of tumor cells, in vitro. Very few data are available on the role of ASC in the treatment of acute myeloid leukemia (AML). Ascorbate behaves as an antioxidant at low (physiologic), and as pro-oxidant at pharmacologic, concentrations, and this may account for the differences reported in different experimental settings, when human myeloid cell lines, such as HL60, were treated with ASC. Considering the myeloid origin of HL60 cells, and previous literature reports showing that some cell lines belonging to the myeloid lineage could be sensitive to the pro apoptotic effects of high concentrations of ASC, we investigated in more details the effects of high doses (0.5 to 7 mM) of ASC in vitro, on a variety of human myeloid cell lines including the following: HL60, U937, NB4, NB4-R4 (retinoic acid [RA]-resistant), NB4/AsR (ATO-resistant) acute promyelocytic leukemia (APL) derived cell lines, and K562 as well as on normal CD34+ progenitors derived from human cord blood. Our results indicate that all analyzed cell lines including all trans retinoic acid (ATRA)- and arsenic trioxide (ATO)-resistant ones are highly sensitive to the cytotoxic, pro-oxidant effects of high doses of ASC, with an average 50 % lethal concentration (LC50) of 3 mM, depending on cell type, ASC concentration, and time of exposure. Conversely, high doses of ASC neither did exert significant cytotoxic effects nor impaired the differentiation potential in cord blood (CB) CD34+ normal cells. Since plasma ASC concentrations within the millimolar (mM) range can be easily and safely reached by intravenous administration, we conclude that phase I/II clinical trials using high doses of ASC should be designed for patients with advanced/refractory AML and APL. PMID- 26264693 TI - Preemptive administration of human alphabeta T cell receptor-targeting monoclonal antibody GZ-alphabetaTCR potently abrogates aggressive graft-versus-host disease in vivo. AB - GVHD, both acute and chronic, remains the major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Thus, there is still a great need for therapeutic tools for the prevention and treatment of GVHD. Several biologics have shown promising results in salvage therapies but are attendant on an increased risk for opportunistic infections, lymphoproliferative disorders, and relapse. This is partly due to efficient T cell elimination that neither dissects alloreactive from non-alloreactive T cells nor considers functional and structural distinctiveness of pathogen- and malignancy-reactive gammadelta and iNKT T cells. A novel, humanized monoclonal antibody, GZ alphabetaTCR, specific for the human alphabeta T cell receptor, was evaluated in a xenogeneic GVHD model for its potential to prevent or ameliorate GVHD and prolong survival. We could show that GZ-alphabetaTCR significantly attenuated clinical signs of GVHD and prolonged survival by preferential depletion of CD4 cells and the naive T cell compartment, the trigger and driver of GVHD. In a regimen that included a preemptive dose, GZ-alphabetaTCR treatment sufficiently abrogated GVHD. Importantly, GZ-alphabetaTCR's specificity spared host cell mediated immune competence of cell types other than alphabetaT cells: namely gammadeltaT cells. GZ-alphabetaTCR's outstanding capacity to prevent GVHD and ameliorate an ongoing GVHD while sparing immune cells other than alphabetaT cells strongly recommends GZ-alphabetaTCR for the prevention and treatment of acute GVHD in clinical settings. PMID- 26264694 TI - Thermodynamics of Abeta16-21 dissociation from a fibril: Enthalpy, entropy, and volumetric properties. AB - Here, we provide insights into the thermodynamic properties of A beta16-21 dissociation from an amyloid fibril using all-atom molecular dynamics simulations in explicit water. An umbrella sampling protocol is used to compute potentials of mean force (PMF) as a function of the distance xi between centers-of-mass of the A beta16-21 peptide and the preformed fibril at nine temperatures. Changes in the enthalpy and the entropic energy are determined from the temperature dependence of these PMF(s) and the average volume of the simulation box is computed as a function of xi. We find that the PMF at 310 K is dominated by enthalpy while the entropic energy does not change significantly during dissociation. The volume of the system decreases during dissociation. Moreover, the magnitude of this volume change also decreases with increasing temperature. By defining dock and lock states using the solvent accessible surface area (SASA), we find that the behavior of the electrostatic energy is different in these two states. It increases (unfavorable) and decreases (favorable) during dissociation in lock and dock states, respectively, while the energy due to Lennard-Jones interactions increases continuously in these states. Our simulations also highlight the importance of hydrophobic interactions in accounting for the stability of A beta16-21. PMID- 26264695 TI - Liquid storage of boar semen: Current and future perspectives on the use of cationic antimicrobial peptides to replace antibiotics in semen extenders. AB - Antibiotics are of great importance in boar semen extenders to ensure long shelf life of spermatozoa and to reduce transmission of pathogens into the female tract. However, the use of antibiotics carries a risk of developing resistant bacterial strains in artificial insemination laboratories and their spread via artificial insemination. Development of multiresistant bacteria is a major concern if mixtures of antibiotics are used in semen extenders. Minimal contamination prevention techniques and surveillance of critical hygiene control points proved to be efficient in reducing bacterial load and preventing development of antibiotic resistance. Nevertheless, novel antimicrobial concepts are necessary for efficient bacterial control in extended boar semen with a minimum risk of evoking antibiotic resistance. Enhanced efforts have been made in recent years in the design and use of antimicrobial peptides (AMPs) as alternatives to conventional antibiotics. The male genital tract harbors a series of endogenic substances with antimicrobial activity and additional functions relevant to the fertilization process. However, exogenic AMPs often exert dose- and time-dependent toxic effects on mammalian spermatozoa. Therefore, it is important that potential newly designed AMPs have only minor impacts on eukaryotic cells. Recently, synthetic magainin derivatives and cyclic hexapeptides were tested for their application in boar semen preservation. Bacterial selectivity, proteolytic stability, thermodynamic resistance, and potential synergistic interaction with conventional antibiotics propel predominantly cyclic hexapeptides into highly promising, leading candidates for further development in semen preservation. The time scale for the development of resistant pathogens cannot be predicted at this moment. PMID- 26264696 TI - Doxycycline shows dose-dependent changes in hernia repair strength after mesh repair. AB - BACKGROUND: Ventral hernia is a commonly occurring surgical problem. Our earlier studies have shown that a 30 mg/kg dose of doxycycline can significantly impact the strength of polypropylene (PP) mesh in a rat hernia repair model at 6 and 12 weeks. The objective of the present study was to investigate the dose dependence of doxycycline treatment on hernia repair strengths in rats. STUDY DESIGN: Fifty six Sprague-Dawley rats underwent hernia repair with either PP mesh (n = 28) or sutures only (primary; n = 28); both groups were further divided into four doxycycline groups of seven animals each: control (0 mg/kg), low (3 mg/kg), medium (10 mg/kg), and high (30 mg/kg). One day before hernia repair surgery, animals received doxycycline doses by gavage and continued receiving daily until euthanasia. After 8 weeks, rats were euthanized and tissue samples from hernia repaired area were collected and analyzed for tensile strength using a tensiometer (Instron, Canton, MA, USA), while MMPs 2, 3, and 9, and collagen type 1 and 3 were analyzed by western blotting. RESULTS: In mesh-repaired animals, medium and high doxycycline dose repaired mesh fascia interface (MFI) showed significant increase in tensile strength when compared to control. In the primary repaired animals, there was no significant difference in MFI tensile strength in any dose group. In medium-dose MFI, there was a significant reduction in MMPs 2, 3, and 9. In this animal group, MFI showed significant increase in collagen 1 and significant reduction in collagen type 3 when compared to control. CONCLUSION: It is possible to improve the strength of mesh-repaired tissue by administering a significantly lower dose of the drug, which has implications for translation of the findings. PMID- 26264697 TI - Transanal endoscopic resection with peritoneal entry: a word of caution. AB - BACKGROUND: Peritoneal entry during transanal endoscopic microsurgery (TEM) can usually be managed transanally with full-thickness suture closure by experienced operators. The preliminary safety of transanal minimally invasive surgery (TAMIS) has been demonstrated, but the reported experience with upper rectal tumors is limited. The incidence and management of peritoneal entry during transanal endoscopic surgery across various platforms have not been previously evaluated. METHODS: Retrospective analysis of a prospectively maintained database of all transanal endoscopic resections performed at a single institution between January 2008 and December 2014 was conducted. Cases with and without peritoneal entry were evaluated with respect to transanal platform used, surgical indication, size, location and distance from the anal verge, and incidence of postoperative complications. RESULTS: A total of 78 transanal endoscopic procedures were performed on 76 patients using the rigid transanal endoscopic operation (TEO, 65.4 %), TEM (26.9 %), and TAMIS platform (7.7 %). The most common surgical indication included endoscopically unresectable adenomas (50 %). The average distance of lesions from the anal verge (AV) was 9.6 cm (range 4-20 cm). Peritoneal entry occurred in 22 cases (28.2 %). Platform used (TAMIS vs. rigid, p < 0.05), mean distance from the AV (p < 0.0001), location along the rectum (p = 0.01), and mean specimen size (p = 0.01) were associated with a higher likelihood of peritoneal entry. All rectal defects associated with peritoneal entry were successfully closed transanally except for two (TEM and TEO) cases that required conversion to laparoscopic low anterior resection and laparoscopic Hartmann's, respectively. There were four TAMIS cases that required conversion to TEO platforms. CONCLUSION: In this high-risk TEM, TEO, and TAMIS series (one-third of rectal lesions located in the upper rectum), 91 % of all peritoneal entries were managed transanally without increased morbidity. TAMIS for upper rectal lesions was associated with a high risk of complicated peritoneal entry requiring conversion to a rigid platform. PMID- 26264698 TI - Matrix Metalloproteinase 9 and Vasodilator-Stimulated Phosphoprotein Related to Acute Kidney Injury in Severe Acute Pancreatitis Rats. AB - BACKGROUND: Severe acute pancreatitis (SAP) usually results in acute renal failure. Matrix metalloproteinase 9 (MMP-9) and vasodilator-stimulated phosphoprotein (VASP) may participate in disease progression. AIM: To investigate the renal expression of MMP-9 and VASP in SAP rats with acute kidney injury. METHODS: A total of 100 rats were randomly assigned to sham 6-h, sham 12-h, sham 24-h, sham 36-h, sham 48-h, SAP 6-h, SAP 12-h, SAP 24-h, SAP 36-h, and SAP 48-h treatment groups (n = 10 per group). Levels of serum amylase (AMY), creatinine (Cr), and blood urea nitrogen (BUN) were determined. Renal pathology and ultrastructural examinations were performed, and renal mRNA and protein expression of MMP-9 and VASP were determined by real-time RT-PCR and Western blot, respectively. The activity of MMP-9 was assessed by gelatin zymography. RESULTS: In the SAP groups, serum levels of AMY, Cr, and BUN were markedly higher than in the sham groups. The peak value of AMY was observed from 12 to 24 h, but that of Cr and BUN was observed at 36 h. Capillary endothelial cells in the renal interstitium were impaired and expression of MMP-9 and VASP in the kidney was significantly increased when compared with the sham groups. Expression of MMP-9 and VASP declined when renal damage reached a maximum after 24 h. CONCLUSIONS: In the presence of acute kidney injury in SAP, the renal expression of MMP-9 and VASP is related to damage of endothelial cells in capillaries, which reached a maximum at 24 h and declined afterwards. PMID- 26264699 TI - Erratum to: Platelet Activation Markers Are Associated with Crohn's Disease Activity in Patients with Low C-Reactive Protein. PMID- 26264700 TI - Functional Gastrointestinal Symptoms Are Associated with Higher Serum Total IgE Levels, but Less Atopic Sensitization. AB - BACKGROUND: The relation of gastrointestinal (GI) complaints to IgE-mediated allergy is not well understood. Increased numbers of "IgE-armed" mast cells have been observed in duodenal mucosa of patients with functional GI complaints. AIMS: To explore whether total IgE and atopic sensitization were associated with functional GI complaints. METHODS: Levels of serum total and specific IgE and GI complaints were measured in 161 patients and in a general population sample of 478 persons. Standard inhalant allergens were measured in the patient group, and selected inhalant allergens in the general population. GI complaints were assessed by two standardized questionnaires. The associations between GI complaints and total IgE were analyzed in multiple regression models. RESULTS: GI complaints were positively associated with higher total IgE levels (all: b = 0.028, p = 0.012; patient group: b = 0.038, p = 0.072; general population: b = 0.038, p = 0.005), but negatively associated with atopic sensitization (all: b = 11.256, p = 0.181; patient group: b = -85.667, p < 0.001; general population: b = -14.394, p = 0.083). The relationship between total IgE and GI complaints was consistent among sensitized and non-sensitized persons, among men and women, and across age groups. CONCLUSION: Serum total IgE was positively associated with GI complaints, while atopic sensitization was inversely associated with GI complaints. This suggests that IgE-mediated immunology plays a role in the pathophysiology of functional GI complaints. The biological mechanisms reflected in higher total IgE levels, but less atopic sensitization, warrant further studies. PMID- 26264701 TI - Impact of fertility preservation counseling and treatment on psychological outcomes among women with cancer: A systematic review. AB - BACKGROUND: For many female cancer survivors, the preservation of reproductive potential is central to quality of life (QOL), and concerns regarding infertility may affect treatment decisions. Despite the existence of several consensus guidelines supporting routine fertility preservation consultation, to the authors' knowledge little is known regarding psychological outcomes in female cancer patients who undergo fertility preservation counseling/consultation (FPC), with or without fertility preservation (FP). METHODS: This literature review examined the effect of FPC alone, or with FP, on psychological outcomes including satisfaction, decisional regret, and QOL. PubMed and PsychINFO were systematically searched for English-language publications from the earliest available publication date of each database through March 2015. Among 111 unique articles concerning oncofertility, 13 met inclusion criteria: peer-reviewed articles reporting primary data regarding satisfaction and psychological outcomes among women who underwent FPC alone or with FP. RESULTS: A majority of women receiving FPC reported that the possibility of FP was instrumental to improved coping. Receiving FPC reduced long-term regret and dissatisfaction concerning fertility, and was associated with improved physical QOL and trends toward improved psychological QOL. Women also desired prompt, standardized, and written information addressing perceived unmet needs specific to oncofertility. Offering FPC was perceived as critical regardless of age or parity. CONCLUSIONS: To the best of the authors' knowledge, little research to date has addressed the impact of FPC alone, or with FP, on QOL in women with cancer. Clinicians should recognize the existing evidence base supporting the psychological benefit of prompt FPC. Future research must be conducted to elucidate the long-term psychosocial effects of FP. PMID- 26264702 TI - CYP-mediated drug-drug interactions with evacetrapib, an investigational CETP inhibitor: in vitro prediction and clinical outcome. AB - AIMS: Evacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor under development for reducing cardiovascular events in patients with high risk vascular disease. CETP inhibitors are likely to be utilized as 'add-on' therapy to statins in patients receiving concomitant medications, so the potential for evacetrapib to cause clinically important drug-drug interactions (DDIs) with cytochromes P450 (CYP) was evaluated. METHODS: The DDI potential of evacetrapib was investigated in vitro, followed by predictions to determine clinical relevance. Potential DDIs with possible clinical implications were then investigated in the clinic. RESULTS: In vitro, evacetrapib inhibited all of the major CYPs, with inhibition constants (K(i)) ranging from 0.57 uM (CYP2C9) to 7.6 uM (CYP2C19). Evacetrapib was a time-dependent inhibitor and inducer of CYP3A. The effects of evacetrapib on CYP3A and CYP2C9 were assessed in a phase 1 study using midazolam and tolbutamide as probe substrates, respectively. After 14 days of daily dosing with evacetrapib (100 or 300 mg), midazolam exposures (AUC) changed by factors (95% CI) of 1.19 (1.06, 1.33) and 1.44 (1.28, 1.62), respectively. Tolbutamide exposures (AUC) changed by factors of 0.85 (0.77, 0.94) and 1.06 (0.95, 1.18), respectively. In a phase 2 study, evacetrapib 100 mg had minimal impact on AUC of co-administered simvastatin vs. simvastatin alone with a ratio of 1.25 (1.03, 1.53) at steady-state, with no differences in reported hepatic or muscular adverse events. CONCLUSIONS: Taken together, the extent of CYP-mediated DDI with the potential clinical dose of evacetrapib is weak and clinically important DDIs are not expected to occur in patients taking concomitant medications. PMID- 26264704 TI - Palbociclib: a first-in-class CDK4/CDK6 inhibitor for the treatment of hormone receptor positive advanced breast cancer. AB - Palbociclib was approved by the FDA for use in combination with letrozole for the treatment of postmenopausal women with hormone-receptor-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy. In addition, the combination of palbociclib with fulvestrant resulted in superior outcome than fulvestrant alone in those who had progressed during prior endocrine therapy. This research highlight summarized the current development of CDK4/CDK6 inhibitors and future directions in the treatment of advanced hormone-receptor positive breast cancer. PMID- 26264703 TI - The Glasgow Benefit Inventory: a systematic review of the use and value of an otorhinolaryngological generic patient-recorded outcome measure. AB - BACKGROUND: The Glasgow Benefit Inventory (GBI) is a validated, generic patient recorded outcome measure widely used in otolaryngology to report change in quality of life post-intervention. OBJECTIVES OF REVIEW: To date, no systematic review has made (i) a quality assessment of reporting of Glasgow Benefit Inventory outcomes; (ii) a comparison between Glasgow Benefit Inventory outcomes for different interventions and objectives; (iii) an evaluation of subscales in describing the area of benefit; (iv) commented on its value in clinical practice and research. TYPE OF REVIEW: Systematic review. SEARCH STRATEGY: 'Glasgow Benefit Inventory' and 'GBI' were used as keywords to search for published, unpublished and ongoing trials in PubMed, EMBASE, CINAHL and Google in addition to an ISI citation search for the original validating Glasgow Benefit Inventory paper between 1996 and January 2015. EVALUATION METHOD: Papers were assessed for study type and quality graded by a predesigned scale, by two authors independently. Papers with sufficient quality Glasgow Benefit Inventory data were identified for statistical comparisons. Papers with <50% follow-up were excluded. RESULTS: A total of 118 eligible papers were identified for inclusion. A national audit paper (n = 4325) showed that the Glasgow Benefit Inventory gave a range of scores across the specialty, being greater for surgical intervention than medical intervention or 'reassurance'. Fourteen papers compared one form of surgery versus another form of surgery. In all but one study, there was no difference between the Glasgow Benefit Inventory scores (or of any other outcome). The most likely reason was lack of power. Two papers took an epidemiological approach and used the Glasgow Benefit Inventory scores to predict benefit. One was for tonsillectomy where duration of sore throat episodes and days with fever were identified on multivariate analysis to predict benefit albeit the precision was low. However, the traditional factor of number of episodes of sore throat was not predictive. The other was surgery for chronic rhinosinusitis where those with polyps on univariate analysis had greater benefit than those without. Forty-three papers had a response rate of >50% and gave sufficient Glasgow Benefit Inventory total and subscales for meta-analysis. For five of the 11 operation categories (vestibular schwannoma, tonsillectomy, cochlear implant, middle ear implant and stapes surgery) that were most likely to have a single clear clinical objective, score data had low-to-moderate heterogeneity. The value in the Glasgow Benefit Inventory having both positive and negative scores was shown by an overall negative score for the management of vestibular schwannoma. The other six operations gave considerable heterogeneity with rhinoplasty and septoplasty giving the greatest percentages (98% and 99%) most likely because of the considerable variations in patient selection. The data from these operations should not be used for comparative purposes. Five papers also reported the number of patients that had no or negative benefit, a potentially a more clinically useful outcome to report. Glasgow Benefit Inventory subscores for tonsillectomy were significantly different from ear surgery suggesting different areas of benefit CONCLUSIONS: The Glasgow Benefit Inventory has been shown to differentiate the benefit between surgical and medical otolaryngology interventions as well as 'reassurance'. Reporting benefit as percentages with negative, no and positive benefit would enable better comparisons between different interventions with varying objectives and pathology. This could also allow easier evaluation of factors that predict benefit. Meta-analysis data are now available for comparison purposes for vestibular schwannoma, tonsillectomy, cochlear implant, middle ear implant and stapes surgery. Fuller report of the Glasgow Benefit Inventory outcomes for non-surgical otolaryngology interventions is encouraged. PMID- 26264705 TI - Bifunctional siRNA containing immunostimulatory motif enhances protection against pandemic H1N1 virus infection. AB - RATIONALE: The first influenza pandemic of 21(st) century was attributed to a novel quadruple reassortant H1N1 virus that emerged in 2009. Currently available therapies for influenza have drugresistant. Therefore, there is a need to develop new generation immunotherapeutic antiviral strategy. This study described the efficacy of a novel bifunctional immunostimulatory siRNAs against H1N1pdm swine flu virus by targeting the Nucleocapsid (NP) gene. METHODS & FINDINGS: Small interfering RNAs (siRNA) targeting conserved region of NP were screened for antiviral efficacy in human lung epithelial cells (A549). Further, a bifunctional siRNA was synthesized by combining immunostimulatory sequence (5'-UGUGU-3') with NP specific siRNA. This immunostimulatory siRNA (NP-1-is) revealed strong antiviral effect through reduction in mRNA copies (99.58%), reduction in virus associated cell apoptosis and inhibition of nucleocapsid protein in western blot. This immunostimulatory siRNA was found more effective than nontagged siRNA. Further studies including dose dependent and time course kinetics revealed that the NP-1-is siRNA is more effective at 20-80 nM with significant protection upto 48 hpi. Besides, the qRT-PCR and western blot analysis confirmed higher antiviral response of immunostimulatory siRNA was due to upregulation of TLR-7 MyD88, IRF-7 and IFN-alpha. CONCLUSIONS: This study paves the way for broad-spectrum RNAi based therapeutics using immunostimulatory motif towards improved antiviral effect. Hence this approach will be useful to confront the sudden emergence of pandemic strains. PMID- 26264706 TI - Folate-conjugated chitosan-poly(ethylenimine) copolymer as an efficient and safe vector for gene delivery in cancer cells. AB - Folic acid (FA) has high affinity to folate receptors (FRs), which have three isoforms: FRalpha, FRbeta and FRgamma. Among them, FRalpha is a tumor specific receptor, as it is frequently over-expressed in diverse malignancies but not in normal tissues. In this study, we have conjugated FA to a chitosan poly(ethylenimine) copolymer, and have confirmed the low cytotoxicity of the product (namely "CP1.3K-FA") in cancer cells. The transfection efficiency of CP1.3K-FA has been shown by the EGFP transfection assay to be higher than that of the unmodified chitosan-poly(ethylenimine) copolymer under optimal conditions. Results of the luciferase activity assay have also indicated that the transfection efficiency of CP1.3K-FA is comparable to that of Fugene HD in B16 and U87 cells. Our results have suggested that CP1.3K-FA warrants further development as a vector for gene delivery in cancer cells. PMID- 26264707 TI - Biodistribution of LV-TSTA transduced rat bone marrow cells used for "ex-vivo" regional gene therapy for bone repair. AB - "Ex vivo" regional gene therapy using lentiviral (LV) vectors to over-express bone morphogenetic protein 2 (BMP-2) is an effective way to enhance bone healing in animal models. Here, we evaluated two different "ex vivo" approaches using either "same day" rat bone marrow cells (SDRBMCs) or cultured rat bone marrow cells (C-RBMCs), both transduced with a LV based two-step transcriptional activation system overexpressing GFP (LV-TSTA-EGFP), to assess the fate of the transduced cells and the safety of this approach. The transduced cells were implanted in femoral defects of syngeneic rats. Animals were sacrificed at 4, 14, 28 and 56 days after surgery (n=5 per group). Viral copies were detectable in the defect site of SD-RBMC group and gradually declined at 8w (5 log decrease compared to 4d). In the C-RBMC animals, there was a 2-4 log decline in the viral copy numbers at 2w and 4w, but at 8w there was a relative rise (about 100 fold) in the number of the viral vectors in the defect site of 4 (out of 5) animals compared to the previous time points. For both gene transfer approaches, the pattern of tissue distribution was non-specific and no histological abnormalities were noted in either group. In summary, we demonstrated that the LV-TSTA transduced cells remain in the defect site for at least 56 days, though the numbers decreased over time. There were no consistent findings of viral copies in internal organs which is encouraging with respect to the development of this strategy for use in humans. PMID- 26264708 TI - CFTR inactivation by lentiviral vector-mediated RNA interference and CRISPR-Cas9 genome editing in human airway epithelial cells. AB - BACKGROUND: Polarized airway epithelial cell cultures modelling Cystic Fibrosis Transmembrane conductance Regulator (CFTR) defect are crucial for CF and biomedical research. RNA interference has proven its value to generate knockdown models for various pathologies. More recently, genome editing using CRISPR-Cas9 artificial endonuclease was a valuable addition to the toolbox of gene inactivation. METHODS: Calu-3 cells and primary HAECs were transduced with HIV-1 derived lentiviral vectors (LVV) encoding small hairpin RNA (shRNA) sequence or CRISPR-Cas9 components targeting CFTR alongside GFP. After sorting of GFP positive cells, CFTR expression was measured by RT-qPCR and Western blot in polarized or differentiated cells. CFTR channel function was assessed in Ussing chambers. Il-8 secretion, proliferation and cell migration were also studied in transduced cells. RESULTS: shRNA interference and CRISPRCas9 strategies efficiently decreased CFTR expression in Calu-3 cells. Strong CFTR knockdown was confirmed at the functional level in CRISPR-Cas9-modified cells. CFTR-specific shRNA sequences did not reduce gene expression in primary HAECs, whereas CRISPR Cas9-mediated gene modification activity was correlated with a reduction of transepithelial secretion and response to a CFTR inhibitor. CFTR inactivation in the CRISPR-Cas9-modified Calu-3 cells did not affect migration and proliferation but slightly increased basal interleukin-8 secretion. CONCLUSION: We generated CFTR inactivated cell lines and demonstrated that CRISPR-Cas9 vectorised in a single LVV efficiently promotes CFTR inactivation in primary HAECs. These results provide a new protocol to engineer CF primary epithelia with their isogenic controls and pave the way for manipulation of CFTR expression in these cultures. PMID- 26264709 TI - Therapy for dominant inherited diseases by allele-specific RNA interference: successes and pitfalls. AB - RNA interference (RNAi) is a conserved mechanism for post-transcriptional gene silencing mediated by messenger RNA (mRNA) degradation. RNAi is commonly induced by synthetic siRNA or shRNA which recognizes the targeted mRNA by base pairing and leads to target-mRNA degradation. RNAi may discriminate between two sequences only differing by one nucleotide conferring a high specificity of RNAi for its target mRNA. This property was used to develop a particular therapeutic strategy called "allele-specific-RNA interference" devoted to silence the mutated allele of genes causing dominant inherited diseases without affecting the normal allele. Therapeutic benefit was now demonstrated in cells from patients and animal models, and promising results of the first phase Ib clinical trial using siRNA based allele-specific therapy were reported in Pachyonychia Congenita, an inherited skin disorder due to dominant mutations in the Keratin 6 gene. Our purpose is to review the successes of this strategy aiming to treat dominant inherited diseases and to highlight the pitfalls to avoid. PMID- 26264710 TI - Overexpression of artificially fused bifunctional enzyme 4CL1-CCR: a method for production of secreted 4-hydroxycinnamaldehydes in Escherichia coli. AB - BACKGROUND: 4-Hydroxycinnamaldehydes are important intermediates in several secondary metabolism pathways, including those involved in the biosynthesis of phenolic acids, flavonoids, terpenoids and monolignols. They are also involved in the biosynthesis and degradation of lignins, which are important limiting factors during the processes of papermaking and biofuel production. Access to these aromatic polymers is necessary to explore the secondary biometabolic pathways they are involved in. Coniferaldehyde, sinapaldehyde, p-coumaraldehyde and caffealdehyde are members of the 4-hydroxycinnamaldehyde family. Although coniferaldehyde and sinapaldehyde can be purchased from commercial sources, p coumaraldehyde and caffealdehyde are not commercially available. Therefore, there is increasing interest in producing 4-hydroxycinnamaldehydes. Here, we attempted to produce 4-hydroxycinnamaldehydes using engineered Escherichia coli. RESULTS: 4 Coumaric acid: coenzyme A ligase (4CL1) and cinnamoyl coenzyme A reductase (CCR) were fused by means of genetic engineering to generate an artificial bifunctional enzyme, 4CL1-CCR, which was overexpressed in cultured E. coli supplemented with phenylpropanoic acids. Three 4-hydroxycinnamaldehydes, p-coumaraldehyde, caffealdehyde and coniferaldehyde, were thereby biosynthesized and secreted into the culture medium. The products were extracted and purified from the culture medium, and identically characterized by the HPLC-PDA-ESI-MSn. The productivity of this new metabolic system were 49 mg/L for p-coumaraldehyde, 19 mg/L for caffealdehyde and 35 mg/L for coniferaldehyde. Extracellular hydroxycinnamoyl coenzyme A thioesters were not detected, indicating that these thioesters could not pass freely through the cellular membrane. The fusion enzyme 4CL1-CCR can catalyze sequential multistep reactions, thereby avoiding the permeability problem of intermediates, which reveals its superiority over a mixture of individual native enzymes. Moreover, we have described a highly sensitive and selective method for separation and identification of phenylpropanoic acids and their corresponding cinnamaldehydes in the present paper. The feasibility of this method has been proven in the application of the method to the analysis of the metabolites of whole-cell catalysts. CONCLUSIONS: We have established a bioconversion pathway for the microbial production of valuable 4 hydroxycinnamaldehydes from phenylpropanoic acids. This biotransformation method is both convenient and environmentally friendly, and provides new insights into the biosynthesis of natural plant secondary products. PMID- 26264711 TI - Comparative studies on radioluminescent and thermoluminescent spectra of LiF:Mg,Cu,P and LiF:Mg,Cu,Si. AB - The influence of various annealing treatments on radioluminescent (RL) and thermoluminescent (TL) spectra of LiF:Mg,Cu,Si and LiF:Mg,Cu,P was investigated. The TL and RL emission bands for LiF:Mg,Cu,P are not the same; however, the emission band peaking at ~383 nm is predominant in the TL and RL emission for LiF:Mg,Cu,Si. With the increase in annealing temperatures in the range of 240-300 degrees C, for LiF:Mg,Cu,P, the intensity of TL decreases much more rapidly than that of RL. For LiF:Mg,Cu,Si, the area ratios of the two bands of RL and TL remain constant within experimental errors. It suggests that there is a significant decrease in the concentration of recombination centres in LiF:Mg,Cu,P after the annealing, in addition to the decrease in trapping centres, the recombination centres for main TL emission and RL emission in LiF:Mg,Cu,Si are the same, and the recombination centres for TL emission and RL emission in LiF:Mg,Cu,P are not the same. P is a more effective dopant than Si. PMID- 26264712 TI - Strong founder effect of p.P240L in CDH23 in Koreans and its significant contribution to severe-to-profound nonsyndromic hearing loss in a Korean pediatric population. AB - BACKGROUND: Despite the prevalence of CDH23 mutations in East Asians, its large size hinders investigation. The pathologic mutation p.P240L in CDH23 is common in East Asians. However, whether this mutation represents a common founder or a mutational hot spot is unclear. The prevalence of CDH23 mutations with prelingual severe-to-profound sporadic or autosomal recessive sensorineural hearing loss (arSNHL) is unknown in Koreans. METHODS: From September 2010 to October 2014, children with severe-to-profound sporadic or arSNHL without phenotypic markers, and their families, were tested for mutations in connexins GJB2, GJB6 and GJB3. Sanger sequencing of CDH23 p.P240L was performed on connexin-negative samples without enlarged vestibular aqueducts (EVA), followed by targeted resequencing of 129 deafness genes, including CDH23, unless p.P240L homozygotes were detected in the first screening. Four p.P240L-allele-linked STR markers were genotyped in 40 normal-hearing control subjects, and the p.P240L carriers in the hearing-impaired cohort, to identify the haplotypes. RESULTS: Four (3.1 %) of 128 children carried two CDH23 mutant alleles, and SLC26A4 and GJB2 accounted for 18.0 and 17.2 %, respectively. All four children showed profound nonsyndromic SNHL with minimal residual hearing. Interestingly, all had at least one p.P240L mutant allele. Analysis of p.P240L-linked STR markers in these children and other postlingual hearing-impaired adults carrying p.P240L revealed that p.P240L was mainly carried on a single haplotype. CONCLUSIONS: p.P240L contributed significantly to Korean pediatric severe arSNHL with a strong founder effect, with implications for future phylogenetic studies. Screening for p.P240L as a first step in GJB2 negative arSNHL Koreans without EVA is recommended. PMID- 26264713 TI - Elective removal of implants after open reduction and internal fixation of Tibial Plateau fractures improves clinical outcomes. AB - INTRODUCTION: Tibial plateau fractures are common injuries often treated with open reduction and internal fixation. We have noted improved patient satisfaction following implant removal for these patients. The purpose of this study was to assess the effect of removal of surgical implants after union on patient reported outcomes. MATERIALS AND METHODS: All patients at our Level 1 Trauma Center undergoing open reduction an internal fixation by the senior surgeon are offered enrollment into a prospective registry and have clinical outcomes recorded at follow-up [Knee Outcomes Survey (KOS), Lower Extremity Functional Scale (LEFS), Short Form-36 Physical and Mental Component Summary (SF-36 PCS, SF-36 MCS), and Visual analog pain scale (VAS)]. Routinely, removal of surgical implants is offered after fracture union resulting in two cohorts: those who had undergone elective removal of surgical implants and those who had not. Outcome scores were compared before and after implant removal as well as between the two study populations at final follow-up. RESULTS: Seventy-five patients were identified as having 12 month outcome scores: 36 (48%) had retained implants; 39 (52%) had implants removed. KOS and LEFS outcomes improved significantly after implant removal (p < 0.05). Clinical outcomes (KOS, SF-36 PCS) were also significantly better in patients who had implants removed compared to those that did not at final follow-up (p < 0.05). There was no statistical difference seen in VAS pain scores. CONCLUSIONS: The results of this study indicate that patients who have elective removal of their surgical implants after open reduction and internal fixation of a tibial plateau fracture have improved clinical outcomes after removal and also demonstrate significantly better outcomes than those who have retained implants at final follow-up. Patients who are unhappy with their clinical result should be counseled that removal of the implant may improve function, but may not improve pain. PMID- 26264714 TI - Mesophase and size manipulation of itraconazole liquid crystalline nanoparticles produced via quasi nanoemulsion precipitation. AB - The fabrication of drug nanoparticles (NPs) with process-mediated tunable properties and performances continues to grow rapidly during the last decades. This study investigates the synthesis and phase tuning of nanoparticulate itraconazole (ITR) mesophases using quasi nanoemulsion precipitation from acetone/water systems to seek out an alternative pathway to the nucleation-based NP formation. ITR liquid crystalline (LC) phases were formed and nematic-smectic mesomorphism was achieved via controlling solvent:antisolvent temperature difference (DeltaTS:AS). The use of DeltaTS:AS=49.5 degrees C was associated with a nematic assembly, while intercalated smectic A layering was observed at DeltaTS:AS=0 degrees C, with both phases confined in the nanospheres at room temperature. The quasi emulsion system has not been investigated at the nanoscale to date and in contrary to the microscale, quasi nanoemulsion was observed over the solvent:antisolvent viscosity ratios of 1:7-1:1.4. Poly(acrylic acid) in the solvent phase exhibited a concentration dependent interaction when ITR formed NPs. This nanodroplet-based approach enabled the preparation of a stable ITR nanodispersion using Poloxamer 407 at 80 degrees C, which was unachievable before using precipitation via nucleation. Findings of this work lay groundwork in terms of rationalised molecular assembly as a tool in designing pharmaceutical LC NPs with tailored properties. PMID- 26264715 TI - Keep calm and carry on: Maintaining self-control when intoxicated, upset, or depleted. AB - This study tested within-person associations between intoxication, negative affect, and self-control demands and two forms of self-control failure, interpersonal conflict, and neglecting responsibilities. Effortful control was hypothesised to act as a buffer, reducing individual susceptibility to these within-person effects. In contrast, reactivity was hypothesised to potentiate the within-person associations. 274 young adults aged 18-27 (56% women, 93% white) completed experience sampling assessments for up to 49 days over the course of 1.3 years. Results indicated independent within-person effects of intoxication, negative affect, and self-control demands on the outcomes. Hypothesised moderating effects of reactivity were not supported. Effortful control did not moderate the effects of self-control demands as expected. However, effortful control exhibited a protective effect when individuals were intoxicated or upset to reduce the likelihood of maladaptive behavioural outcomes. PMID- 26264716 TI - Contributions of a global network of tree diversity experiments to sustainable forest plantations. AB - The area of forest plantations is increasing worldwide helping to meet timber demand and protect natural forests. However, with global change, monospecific plantations are increasingly vulnerable to abiotic and biotic disturbances. As an adaption measure we need to move to plantations that are more diverse in genotypes, species, and structure, with a design underpinned by science. TreeDivNet, a global network of tree diversity experiments, responds to this need by assessing the advantages and disadvantages of mixed species plantations. The network currently consists of 18 experiments, distributed over 36 sites and five ecoregions. With plantations 1-15 years old, TreeDivNet can already provide relevant data for forest policy and management. In this paper, we highlight some early results on the carbon sequestration and pest resistance potential of more diverse plantations. Finally, suggestions are made for new, innovative experiments in understudied regions to complement the existing network. PMID- 26264718 TI - The modulation of corticosteroid metabolism by hydrocortisone therapy in patients with hypopituitarism increases tissue glucocorticoid exposure. AB - CONTEXT: Patients with hypopituitarism have increased morbidity and mortality. There is ongoing debate about the optimum glucocorticoid (GC) replacement therapy. OBJECTIVE: To assess the effect of GC replacement in hypopituitarism on corticosteroid metabolism and its impact on body composition. DESIGN AND PATIENTS: We assessed the urinary corticosteroid metabolite profile (using gas chromatography/mass spectrometry) and body composition (clinical parameters and full body DXA) of 53 patients (19 female, median age 46 years) with hypopituitarism (33 ACTH-deficient/20 ACTH-replete) (study A). The corticosteroid metabolite profile of ten patients with ACTH deficiency was then assessed prospectively in a cross over study using three hydrocortisone (HC) dosing regimens (20/10 mg, 10/10 mg and 10/5 mg) (study B) each for 6 weeks. 11 beta hydroxysteroid dehydrogenase 1 (11beta-HSD1) activity was assessed by urinary THF+5alpha-THF/THE. SETTING: Endocrine Centres within University Teaching Hospitals in the UK and Ireland. MAIN OUTCOME MEASURES: Urinary corticosteroid metabolite profile and body composition assessment. RESULTS: In study A, when patients were divided into three groups - patients not receiving HC and patients receiving HC<=20 mg/day or HC>20 mg/day - patients in the group receiving the highest daily dose of HC had significantly higher waist-to-hip ratio (WHR) than the ACTH replete group. They also had significantly elevated THF+5alpha-THF/THE (P=0.0002) and total cortisol metabolites (P=0.015). In study B, patients on the highest HC dose had significantly elevated total cortisol metabolites and all patients on HC had elevated THF+5alpha-THF/THE ratios when compared to controls. CONCLUSIONS: In ACTH-deficient patients daily HC doses of >20 mg/day have increased WHR, THF+5alpha-THF/THE ratios and total cortisol metabolites. GC metabolism and induction of 11beta-HSD1 may play a pivitol role in the development of the metabolically adverse hypopituitary phenotype. PMID- 26264719 TI - Genetics of primary bilateral macronodular adrenal hyperplasia: a model for early diagnosis of Cushing's syndrome? AB - Long-term consequences of cortisol excess are frequent despite appropriate treatment after cure of Cushing's syndrome. This might be due to diagnostic delay, often difficult to reduce in rare diseases. The identification of a genetic predisposing factor might help to improve early diagnosis by familial screening. Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of Cushing's syndrome. Hypercortisolism in PBMAH is most often diagnosed between the fifth and sixth decades of life. The bilateral nature of the adrenocortical tumors and the occurrence of rare clear familial forms suggest a genetic origin. Indeed, a limited subset of PBMAH can be observed as part of multiple tumors syndromes due to alterations of the APC, Menin or Fumarate Hydratase genes. Rare variants of the phosphodiesterases PDE11A have been associated with PBMAH. The recent identification of ARMC5 germline alterations in 25-50% of PBMAH patients without obvious familial history or associated tumors opens new perspectives. ARMC5 alterations follow the model of a tumor suppressor gene: a first germline inactivating mutation of this 16p located gene is followed by a somatic secondary hit on the other allele (inactivating mutation or allelic loss). Functional studies demonstrate that ARMC5 controls apoptosis and steroid synthesis. The phenotype of index cases patients with the mutation seems more severe than the one of WT index cases. However, phenotype variability within a family is often observed. This review summarizes the genetics of PBMAH, focusing on ARMC5, which offer new perspectives for early diagnosis of Cushing's syndrome. PMID- 26264717 TI - Outcome of corticosteroid administration in autoimmune pulmonary alveolar proteinosis: a retrospective cohort study. AB - BACKGROUND: Although no report has demonstrated the efficacy of corticosteroid therapy for autoimmune pulmonary alveolar proteinosis (aPAP), we sometimes encounter patients who have received this therapy for various reasons. However, as corticosteroids can suppress alveolar macrophage function, corticosteroid therapy might worsen disease severity and increase the risk of infections. METHODS: For this retrospective cohort study, we sent a screening form to 165 institutions asking for information on aPAP patients treated with corticosteroids. Of the resulting 45 patients screened, 31 were enrolled in this study. We collected demographic data and information about corticosteroid treatment period, dose, disease severity score (DSS) over the treatment period, and complications. RESULTS: DSS deteriorated during corticosteroid therapy in 23 cases (74.1 %) and the estimated overall cumulative worsening rate was 80.8 % for the total observation period. The worsening rate was significantly higher in patients treated with high-dose prednisolone (>18.9 mg/day, n = 16) than treated with low-dose prednisolone (<=18.9 mg/day, n = 15) divided by median daily dose (p < 0.02). Of patients with worsening, one died of disseminated aspergillosis and another of respiratory failure. Infections newly emerged in 6 cases during corticosteroid therapy (p < 0.05). Median serum granulocyte/macrophage colony stimulating factor (GM-CSF) autoantibody levels were similar to previously reported data in a large cohort study. CONCLUSION: The results demonstrate that corticosteroid therapy may worsen DSS of aPAP, increasing the risk for infections. PMID- 26264720 TI - The growth response to GH treatment is greater in patients with SHOX enhancer deletions compared to SHOX defects. AB - OBJECTIVE: Short stature caused by point mutations or deletions of the short stature homeobox (SHOX) gene (SHOX haploinsufficiency (SHI)) is a registered indication for GH treatment. Patients with a SHOX enhancer deletion (SED) have a similar phenotype, but their response to GH is unknown. It is uncertain if duplications of SHOX or its enhancer (SDUP) cause short stature. This study aimed to describe the clinical characteristics and growth response to GH treatment in patients with aberrations of SHOX and its enhancers. DESIGN: In this retrospective multi-center study (2002-March 2014) clinical information was available from 130 patients (72 SHI, 44 SED, and 14 SDUP) of whom 52 patients were treated with GH. We evaluated height, sitting height (SH), arm span, dysmorphic features and indicators of the growth response to GH (delta height SDS, height velocity, and index of responsiveness). RESULTS: Patients with SEDs showed similar HtSDS to patients with SHI (-2.3 and -2.6, respectively, P=0.2), but they were less disproportionate (SH/height ratio SDS 2.0 vs 3.1 (P<0.01) and extremities/trunk ratio 2.57 vs 2.43 (P=0.03)). The 1st year growth response to GH treatment was significantly greater in prepubertal patients with SEDs than SHI. None of the patients with an SDUP was disproportionate and SDUP cosegregated poorly with short stature; their growth response to GH treatment (n=3) was similar to the other groups. CONCLUSIONS: Patients with SEDs are equally short, but less disproportionate than patients with SHI, and show a greater response to GH. PMID- 26264721 TI - Nearly Missed: Postpartum Type B Aortic Dissection. PMID- 26264722 TI - Determinants of physical activity in minimally impaired people with multiple sclerosis. AB - OBJECTIVE: Despite the commonly known benefits of physical activity, evidence shows that people with multiple sclerosis (pwMS) are relatively inactive. There are several studies about factors affecting physical activity in pwMS. However, these factors have not investigated in minimally impaired pwMS who do not have remarkable symptoms and walking disturbance. The objective was to determine factors affecting physical activity in minimally impaired pwMS. PATIENTS AND METHODS: We recruited 52 minimally impaired pwMS and measured physical activity with Godin Leisure-Time Exercise Questionnaire (GLTEQ) and an accelerometer used for the 7-day period. Demographic data were recorded. Walking (speed, endurance, dexterity, and quality), fatigue, depression, and quality of life were measured. METHODS: We recruited 52 minimally impaired pwMS and measured physical activity with Godin Leisure-Time Exercise Questionnaire (GLTEQ) and an accelerometer used for the 7-day period. Demographic data were recorded. Walking (speed, endurance, dexterity, and quality), fatigue, depression, and quality of life were measured. RESULTS: The walking speed assessed by the Timed 25-Foot Walk and gender were found the determinants of physical activity level assessed by the GLTEQ and accelerometer, respectively. Walking (speed, endurance, and dexterity), gender, employment status, and quality of life were associated with physical activity. Either female or unemployed participants had significantly less physical activity. There were no significant difference between physical activity levels and the other subgroups. CONCLUSION: Either to be a female or to have slower walking speed was associated with less physical activity. Strategies to improve walking should be focused on female pwMS with minimal impairment. PMID- 26264723 TI - Cerebellar white matter changes in patients with newly diagnosed partial epilepsy of unknown etiology. AB - OBJECTIVE: We hypothesize that pre-existing susceptible structures in the brain may be associated with the development of newly diagnosed partial epilepsy of unknown etiology. METHODS: Twenty-two patients with newly diagnosed partial epilepsy of unknown etiology and 36 healthy controls were enrolled in this study. In addition, we included 24 patients with chronic partial epilepsy of unknown etiology as a disease control group. We analyzed whole-brain T1-weighted MRIs using FreeSurfer 5.1. The volumes of the hippocampus, amygdala, thalamus, caudate, putamen, pallidum, brainstem, cerebellar gray and white matter, as well as cerebral gray and white matter were compared between the groups. We also analyzed the changes in brain volumes associated with the chronicity of epilepsy in the patients with chronic epilepsy compared to newly diagnosed epilepsy. RESULTS: The volume of cerebellar white matter in patients with newly diagnosed epilepsy was significantly smaller than that which was observed in the healthy controls (p=0.0001). This finding was also observed in patients with chronic epilepsy (p<0.0001). Cerebral white matter volume was negatively correlated with the duration of epilepsy (r=-0.4, p=0.04). CONCLUSION: These findings support our hypothesis that cerebellar white matter changes may constitute a pre-existing susceptible structure in the brain that is associated with the development of partial epilepsy of unknown etiology. In addition, cerebral white matter was the structure that was the most vulnerable to the progression of epilepsy. PMID- 26264724 TI - Blame Attributions of Victims and Perpetrators: Effects of Victim Gender, Perpetrator Gender, and Relationship. AB - Although research has been conducted on rape myth acceptance (RMA) and other factors associated with attribution formation, researchers have not yet determined how the combination of such factors simultaneously affects levels of victim blame and perpetrator blame. The current investigation recruited 221 students from an all-women's college to examine differences in blame attributions across RMA, victim gender, and perpetrator gender, and the relationship between the two parties (i.e., stranger vs. acquaintance). Results suggested that RMA, victim gender, and perpetrator gender account for a significant amount of variance in blame attributions for both victims and perpetrators. In sum, victim blame with female perpetrators was relatively consistent across levels of RMA, but increased substantially for male perpetrators as individuals endorsed higher levels of RMA. Perpetrator blame, however, was highest with male perpetrators when individuals endorsed low levels of RMA and lowest for male perpetrators when individuals endorsed relatively higher levels of RMA. Findings demonstrate the continued influence of RMA on blame attributions for both victims and perpetrators, and the stigma faced by male victims. More research is needed on the differing attributions of male and female victims and perpetrators, as well as differing attributions based on type of relationship. Such research will lead to a better and more thorough understanding of sexual assault and rape. PMID- 26264725 TI - Gendered Pathways From Child Abuse to Adult Crime Through Internalizing and Externalizing Behaviors in Childhood and Adolescence. AB - Gender differences in externalizing and internalizing pathways from child abuse to adult crime were examined across four waves of an extended longitudinal study ( N = 186 males and 170 females) using multiple-group structural equation modeling. Results show that child abuse was associated with both internalizing and externalizing behaviors in the elementary school years for both males and females. However, gender differences were found such that internalizing behaviors increased the risk of adult crime for females only, and externalizing behaviors increased the risk of adult crime for males only. Internalizing behaviors among males actually lessened the risk of adult crime, and externalizing behaviors were unrelated to adult crime among females. Findings confirm distinct pathways leading from child abuse to later crime for males and females, which is important for prevention and intervention strategies. PMID- 26264726 TI - Drospirenone enhances GPIb-IX-V-mediated platelet activation. AB - BACKGROUND: Epidemiologic studies recently revealed that using drospirenone (DRSP)-containing contraceptives is associated with an increased risk of thrombosis in women. However, the underlying causality is unclear. OBJECTIVE: To study the effects of DRSP on coagulation in vitro and the probable mechanisms involved. METHODS: First, the effects of DRSP on the activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen (FIB) were measured. Then, the effects of DRSP on platelet activation were investigated in response to low levels of collagen, adenosine 5'-diphosphate (ADP), thrombin, U46619, adrenaline and botrocetin/von Willebrand factor (VWF). RESULTS: DRSP has no direct effect on APTT, PT, TT, FIB and platelet aggregation induced by low levels of collagen, ADP, thrombin, U46619 or adrenaline. However, DRSP enhances botrocetin/VWF-induced platelet aggregation and VWF receptor glycoprotein Ib-IX-V (GPIb-IX-V)-mediated signaling. This enhancement can be blocked by the progesterone receptor membrane component 1 (PGRMC1) inhibitor AG205, or by the ADP scavenger apyrase and the cyclooxygenase inhibitor indomethacin. CONCLUSIONS: Although DRSP did not directly induce platelet activation, it obviously facilitated VWF receptor GPIb-IX-V-mediated platelet activation. The potential DRSP-binding protein PGRMC1 may play a role in this process. Our study also suggested that the inhibition of thromboxane A2 production and the activation of ADP receptors might prevent the side-effects of DRSP. PMID- 26264727 TI - Differences in proxy-reported and patient-reported outcomes: assessing health and functional status among medicare beneficiaries. AB - BACKGROUND: Proxy responses are very common when surveys are conducted among the elderly or disabled population. Outcomes reported by proxy may be systematically different from those obtained from patients directly. The objective of the study is to examine the presence, direction, and magnitude of possible differences between proxy-reported and patient-reported outcomes in health and functional status measures among Medicare beneficiaries. METHODS: This study is a pooled cross-sectional study of a nationally representative sample of community-dwelling Medicare beneficiaries from 2006 to 2011. Survey respondents can respond to the Medicare Current Beneficiary Survey either by themselves or via proxies. Health and functional status was assessed across five domains: physical, affective, cognitive, social, and sensory status. Propensity score matching was used to get matched pairs of patient-reports and proxy-reports. RESULTS: After applying the propensity score matching, the study identified 7,780 person-years of patient reports paired with 7,780 person-years of proxy-reports. Except for the sensory limitation, differences between proxy-reported and patient-reported outcomes were present in physical, affective, cognitive, and social limitations. Compared to patient-reports, a question regarding survey respondents' difficulties in managing money was associated with the largest proxy response bias (relative risk, RR = 3.83). With few exceptions, the presence, direction, and magnitude of differences between proxy-reported and patient-reported outcomes did not vary much in the subgroup analysis. CONCLUSIONS: When there is a difference between proxy-reported and patient-reported outcomes, proxies tended to report more health and functional limitations among the elderly and disabled population. The extent of proxy response bias depended on the domain being tested and the nature of the question being asked. Researchers should accept proxy reports for sensory status and objective, observable, or easy questions. For physical, affective, cognitive, or social status and private, unobservable, or complex questions, proxy-reported outcomes should be used with caution when patient-reported outcomes are not available. PMID- 26264728 TI - Psychiatric assessment is a necessary part of humane care. PMID- 26264730 TI - Correction to A 90 Day Safety Assessment of Genetically Modified Rice Expressing Cry1Ab/1Ac Protein Using an Aquatic Animal Model. PMID- 26264729 TI - 17beta-Estradiol modulates huntingtin levels in rat tissues and in human neuroblastoma cell line. AB - 17beta-Estradiol (E2) exerts neurotrophic and neuroprotective functions in the brain. Here, E2-induced increased levels of huntingtin (HTT), a protein involved in several crucial neuronal functions is reported. E2 physiological concentrations up-regulate HTT in hippocampus and striatum of rats as well as in human neuroblastoma cells. This effect requires both nuclear and extra-nuclear estrogen receptor (ER)alpha activities. Intriguingly, HTT silencing completely prevents E2 protective effects against oxidative stress injury. In conclusion, these data indicate for the first time that HTT is an E2-inducible protein involved in the first steps of E2-induced signaling pathways committed to neuronal protection against oxidative stress. PMID- 26264731 TI - A Rotatable Quality Control Phantom for Evaluating the Performance of Flat Panel Detectors in Imaging Moving Objects. AB - As the use of diagnostic X-ray equipment with flat panel detectors (FPDs) has increased, so has the importance of proper management of FPD systems. To ensure quality control (QC) of FPD system, an easy method for evaluating FPD imaging performance for both stationary and moving objects is required. Until now, simple rotatable QC phantoms have not been available for the easy evaluation of the performance (spatial resolution and dynamic range) of FPD in imaging moving objects. We developed a QC phantom for this purpose. It consists of three thicknesses of copper and a rotatable test pattern of piano wires of various diameters. Initial tests confirmed its stable performance. Our moving phantom is very useful for QC of FPD images of moving objects because it enables visual evaluation of image performance (spatial resolution and dynamic range) easily. PMID- 26264732 TI - The effect of aging on vertical postural control during the forward and backward shift of the center of pressure. AB - Preventing fall-related injuries is becoming a priority as the world population ages. This study's purpose was to examine the effect of aging on vertical postural control in the community-dwelling elderly. Thirty-six elderly individuals and twenty-two healthy young adults were asked to shift their centers of pressure (COPs) as far as possible while standing. The COP position, angle of each lower leg joint, and postural muscle activities were measured using a force plate, three-dimensional motion analyzer, and electromyogram, respectively. The vertical position of the center of mass (COM) was also measured to assess the change in vertical postural control. The backward COP shift in the elderly group was significantly smaller than that in the young group, and both the forward and backward COM shifts were significantly smaller in elders relative to those in youths. The COM position in the elderly group during the backward COP shift was also significantly lower than that in the young group. Knee and ankle joint movements differed between the two groups during the backward COP shift. Factor analysis indicated that dorsal and ventral muscle groups were involved in the COP shift. Specifically, the relationship between the biceps femoris muscle and the voluntary COP shift was reinforced in the elderly group. These findings suggest that the vertical postural strategy changes in the elderly during the backward COP shift. PMID- 26264733 TI - Squaring the circle: a priority-setting method for evidence-based service development, reconciling research with multiple stakeholder views. AB - BACKGROUND: This study demonstrates a technique to aid the implementation of research findings through an example of improving services and self-management in longer-term depression. In common with other long-term conditions, policy in this field requires innovation to be undertaken in the context of a whole system of care, be cost-effective, evidence-based and to comply with national clinical guidelines. At the same time, successful service development must be acceptable to clinicians and service users and choices must be made within limited resources. This paper describes a novel way of resolving these competing requirements by reconciling different sources and types of evidence and systematically engaging multiple stakeholder views. METHODS: The study combined results from mathematical modelling of the care pathway, research evidence on effective interventions and findings from qualitative research with service users in a series of workshops to define, refine and select candidate service improvements. A final consensus-generating workshop used structured discussion and anonymised electronic voting. This was followed by an email survey to all stakeholders, to achieve a pre-defined criterion of consensus for six suggestions for implementation. RESULTS: An initial list of over 20 ideas was grouped into four main areas. At the final workshop, each idea was presented in person, visually and in writing to 40 people, who assigned themselves to one or more of five stakeholder groups: i) service users and carers, ii) clinicians, iii) managers, iv) commissioners and v) researchers. Many belonged to more than one group. After two rounds of voting, consensus was reached on seven ideas and one runner up. The survey then confirmed the top six ideas to be tested in practice. CONCLUSIONS: The method recruited and retained people with diverse experience and views within a health community and took account of a full range of evidence. It enabled a diverse group of stakeholders to travel together in a direction that converged with the messages coming out of the research and successfully yielded priorities for service improvement that met competing requirements. PMID- 26264734 TI - Functional insights from molecular modeling, docking, and dynamics study of a cypoviral RNA dependent RNA polymerase. AB - Antheraea mylitta cytoplasmic polyhedrosis virus (AmCPV) contains 11 double stranded RNA genome segments and infects tasar silkworm A. mylitta. RNA-dependent RNA polymerase (RdRp) is reported as a key enzyme responsible for propagation of the virus in the host cell but its structure function relationship still remains elusive. Here a computational approach has been taken to compare sequence and secondary structure of AmCPV RdRp with other viral RdRps to identify consensus motifs. Then a reliable pairwise sequence alignment of AmCPV RdRp with its closest sequence structure homologue lambda3 RdRp is done to predict three dimensional structure of AmCPV RdRp. After comparing with other structurally known viral RdRps, important sequence and/or structural features involved in substrate entry or binding, polymerase reaction and the product release events have been identified. A conserved RNA pentanucleotide (5'-AGAGC-3') at the 3'-end of virus genome is predicted as cis-acting signal for RNA synthesis and its docking and simulation study along with the model of AmCPV RdRp has allowed to predict mode of template binding by the viral polymerase. It is found that template RNA enters into the catalytic center through nine sequence-independent and two sequence-dependent interactions with the specific amino acid residues. However, number of sequence dependent interactions remains almost same during 10 nano-second simulation time while total number of interactions decreases. Further, docking of N(7)-methyl-GpppG (mRNA cap) on the model as well as prediction of RNA secondary structure has shown the template entry process in the active site. These findings have led to postulate the mechanism of RNA-dependent RNA polymerization process by AmCPV RdRp. To our knowledge, this is the first report to evaluate structure function relationship of a cypoviral RdRp. PMID- 26264735 TI - Testing the efficacy of web-based cognitive behavioural therapy for adult patients with chronic fatigue syndrome (CBIT): study protocol for a randomized controlled trial. AB - BACKGROUND: Cognitive behavioural therapy (CBT) is an effective treatment for fatigue and disabilities in patients with chronic fatigue syndrome (CFS). However, treatment capacity is limited. Providing web-based CBT and tailoring the amount of contact with the therapist to the individual needs of the patient may increase the efficiency of the intervention. Web-based CBT for adolescents with CFS has proven to be effective in reducing fatigue and increasing school attendance. In the proposed study the efficacy of a web-based CBT intervention for adult patients with CFS will be explored. Two different formats of web-based CBT will be tested. In the first format named protocol driven feedback, patients report on their progress and receive feedback from a therapist according to a preset schedule. In the second format named support on demand, feedback and support of the therapist is only given when patients ask for it. The primary objective of the study is to determine the efficacy of a web-based CBT intervention on fatigue severity. METHOD/DESIGN: A randomized clinical trial will be conducted. Two-hundred-forty adults who have been diagnosed with CFS according to the US Centers for Disease Control and Prevention (CDC) consensus criteria will be recruited and randomized to one of three conditions: web-based CBT with protocol driven feedback, web-based CBT with support on demand, or wait list. Feedback will be delivered by therapists specialized in CBT for CFS. Each of the web-based CBT interventions will be compared to a wait list condition with respect to its effect on the primary outcome measure; fatigue severity. Secondary outcome measures are level of disability, physical functioning, psychological distress, and the proportion of patients with clinical significant improvement in fatigue severity. Outcomes will be assessed at baseline and six months post randomization. The web-based CBT formats will be compared with respect to the time therapists need to deliver the intervention. DISCUSSION: As far as we know this is the first randomized controlled trial (RCT) that evaluates the efficacy of a web-based CBT intervention for adult patients with CFS. TRIAL REGISTRATION: NTR4013. PMID- 26264736 TI - System-level understanding of the potential acid-tolerance components of Acidithiobacillus thiooxidans ZJJN-3 under extreme acid stress. AB - In previous study, two extremely acidophilic strains Acidithiobacillus thiooxidans ZJJN-3 (collection site: bioleaching leachate) and ZJJN-5 (collection site: bioleaching wastewater) were isolated from a typical industrial bio-heap in China. Here, we unraveled the potential acid-tolerance components of ZJJN-3 by comparing the physiological differences with ZJJN-5 under different acid stresses. The parameters used for comparison included intracellular pH (pHin), capsule morphology, fatty acid composition of cell membrane, transcription of key molecular chaperones, H(+)-ATPase activities and NAD(+)/NADH ratio. It was indicated that the acid-tolerance of A. thiooxidans ZJJN-3 was systematically regulated. Capsule first thickened and then shed off along with increased acid stress. Cell membrane maintained the intracellular stability by up-regulating the proportion of unsaturated fatty acid and cyclopropane fatty acids. Meanwhile, the transcription of key repair molecular chaperones (GrpE-DnaK-DnaJ) was up regulated by 2.2-3.5 folds for ensuring the proper folding of peptide. Moreover, low pHin promoted ZJJN-3 to biosynthesize more H(+)-ATPase for pumping H(+) out of cells. Furthermore, the NAD(+)/NADH ratio increased due to the decreased H(+) concentration. Based on the above physiological analysis, the potential acid tolerance components of A. thiooxidans ZJJN-3 were first proposed and it would be useful for better understanding how these extremophiles responded to the high acid stress. PMID- 26264737 TI - Using IT to improve access, communication, and asthma in African American and Hispanic/Latino Adults: Rationale, design, and methods of a randomized controlled trial. AB - Asthma morbidity is high among inner-city minority adults. Improving access to care and patient-provider communication are believed to be essential for improving outcomes. Access and communication in turn increasingly rely on information technology including features of the Electronic Health Record. Its patient portal offers web-based communication with providers and practices. How patients with limited resources and educational opportunities can benefit from this portal is unclear. In contrast, home visits by community health workers (CHWs) have improved access to care for asthmatic children and promoted caretaker clinician communication. We describe the planning, design, and methodology of an ongoing randomized controlled trial for 300 adults, predominantly African American and Hispanic/Latino, with uncontrolled asthma recruited from low income urban neighborhoods who are directed to the most convenient internet access and taught to use the portal, with and without home visits from a CHW. The study 1) compares the effects of the 1-year interventions on asthma outcomes (improved asthma control, quality of life; fewer ED visits and hospitalizations for asthma or any cause), 2) evaluates whether communication (portal use) and access (appointments made/kept) mediate the interventions' effects on asthma outcomes, and 3) investigates effect modification by literacy level, primary language, and convenience of internet access. In home visits, CHWs 1) train patients to competency in portal use, 2) enhance care coordination, 3) communicate the complex social circumstances of patients' lives to providers, and 4) compensate for differences in patients' health literacy skills. The practical challenges to design and implementation in the targeted population are presented. PMID- 26264738 TI - Graphene Quantum Dot Layers with Energy-Down-Shift Effect on Crystalline-Silicon Solar Cells. AB - Graphene quantum dot (GQD) layers were deposited as an energy-down-shift layer on crystalline-silicon solar cell surfaces by kinetic spraying of GQD suspensions. A supersonic air jet was used to accelerate the GQDs onto the surfaces. Here, we report the coating results on a silicon substrate and the GQDs' application as an energy-down-shift layer in crystalline-silicon solar cells, which enhanced the power conversion efficiency (PCE). GQD layers deposited at nozzle scan speeds of 40, 30, 20, and 10 mm/s were evaluated after they were used to fabricate crystalline-silicon solar cells; the results indicate that GQDs play an important role in increasing the optical absorptivity of the cells. The short-circuit current density was enhanced by about 2.94% (0.9 mA/cm(2)) at 30 mm/s. Compared to a reference device without a GQD energy-down-shift layer, the PCE of p-type silicon solar cells was improved by 2.7% (0.4 percentage points). PMID- 26264739 TI - Predictive value of left atrial deformation on prognosis in severe primary mitral regurgitation. AB - BACKGROUND: Impaired left atrial (LA) deformation is noted in patients with severe primary mitral regurgitation (MR), but its prognostic value is unknown. The aim of this study was to investigate the prognostic significance of LA deformation parameters in patients with chronic severe primary MR. METHODS: A total of 104 patients with asymptomatic chronic severe primary MR (Carpentier type II) and preserved left ventricular systolic function were prospectively recruited. Global peak positive strain of the left atrium (LASp) and strain rate in the LA filling phase (LASRr) as well as strain rate in the LA conduit phase were identified using two-dimensional speckle-tracking echocardiography. RESULTS: During a mean follow-up period of 13.2 +/- 9.5 months, 22 patients reached a composite end point of death and mitral valve repair or replacement prompted by heart failure development. Among the clinical and echocardiographic parameters, LV end-systolic volume index (19.5 +/- 9.5 vs 15.7 +/- 6.3 mL/m(2), P = .028), LASp (22.7 +/- 10.4% vs 27.2 +/- 9.1%, P = .049), and LASRr (1.97 +/- 0.6 vs 2.33 +/- 0.6 1/sec, P = .013) varied between the two groups in terms of end points but not age, LA volume index, left ventricular ejection fraction, pulmonary artery systolic pressure, and presence of atrial fibrillation. After multivariate analysis, low LASp (odds ratio, 3.606; 95% CI, 1.294-10.052; P = .014) and low LASRr (odds ratio, 2.857; 95% CI, 1.078-7.572; P = .035) remained powerful outcome indicators. CONCLUSIONS: In patients with asymptomatic severe primary MR, reduced LASp and LASRr predicted a worse prognosis. These findings may offer additional information to guide early surgery. PMID- 26264740 TI - Thermodynamic and Structural Evidence for Reduced Hydrogen Bonding among Water Molecules near Small Hydrophobic Solutes. AB - The structure of water molecules near a hydrophobic solute remains elusive despite a long history of scrutiny. Here, we re-examine the subtle issue by a combination of thermodynamic analysis for Henry's constants of several nonpolar gases over a broad range of temperatures and molecular dynamic simulations for the water structure in the hydration shell using several popular semiempirical models of liquid water. Both the structural and thermodynamic data indicate that hydrophobic hydration reduces the degree of the hydrogen bonding among water molecules, and the effect becomes more prominent at high temperatures. Hydrogen bond formation is slightly hindered near a hydrophobic solute due to the restriction of the degree of freedom for water molecules in the solvation shell, and the confinement effect becomes more significant as temperature increases. Reduction in the extent of hydrogen bonding is fully consistent with a positive contribution of a small hydrophobic solute to the solution heat capacity. As predicted by the scaled-particle theory, both Henry's constants and simulation results suggest that the hydration entropy is determined primarily by cavity formation in liquid water, with its magnitude rising with the solute size but declining with temperature. PMID- 26264741 TI - A conserved histidine in switch-II of EF-G moderates release of inorganic phosphate. AB - Elongation factor G (EF-G), a translational GTPase responsible for tRNA-mRNA translocation possesses a conserved histidine (H91 in Escherichia coli) at the apex of switch-II, which has been implicated in GTPase activation and GTP hydrolysis. While H91A, H91R and H91E mutants showed different degrees of defect in ribosome associated GTP hydrolysis, H91Q behaved like the WT. However, all these mutants, including H91Q, are much more defective in inorganic phosphate (Pi) release, thereby suggesting that H91 facilitates Pi release. In crystal structures of the ribosome bound EF-G*GTP a tight coupling between H91 and the gamma-phosphate of GTP can be seen. Following GTP hydrolysis, H91 flips ~140 degrees in the opposite direction, probably with Pi still coupled to it. This, we suggest, promotes Pi to detach from GDP and reach the inter-domain space of EF G, which constitutes an exit path for the Pi. Molecular dynamics simulations are consistent with this hypothesis and demonstrate a vital role of an Mg(2+) ion in the process. PMID- 26264742 TI - Abrogated cardioprotective effect of ischemic preconditioning in ovariectomized rat heart. AB - BACKGROUND: Ischemic heart disease is the leading cause of death in postmenopausal women. The expression of caveolin, a membrane protein and a negative regulator of nitric oxide (NO), increases after menopause. The present study was designed to determine the effect of daidzein (DDZ), a phytoestrogen in attenuated cardioprotective effect of ischemic preconditioning (IPC) in ovariectomized rat heart. METHODS: Heart was isolated from ovariectomized rat and mounted on Langendorff's apparatus, subjected to 30 min ischemia and 120 min reperfusion. IPC was mediated by four cycles of 5 min ischemia and 5 min reperfusion. The infarct size was estimated using triphenyltetrazolium chloride stain, and coronary effluent was analyzed for lactate dehydrogenase and creatine kinase MB (CK-MB) release to assess the degree of myocardial injury. The release of NO was estimated indirectly by measuring the release of nitrite in coronary effluent. RESULTS: IPC-induced cardioprotection was significantly attenuated in ovariectomized rats as compared to normal rats, which was restored by treatment of DDZ, a caveolin inhibitor (0.2 mg/kg subcutaneously) for 1 week. However, this observed cardioprotection was significantly attenuated by perfusion of l nitroarginine methyl ester, an endothelial nitric oxide synthase (eNOS) inhibitor (100 uM/L) and glibenclamide, an adenosine triphosphate-sensitive potassium ion channel blocker (10 uM/L) alone or in combination, noted in terms of increase in myocardial infarct size, release of LDH and CK-MB, and also decrease in the release of NO. CONCLUSION: Thus, it is suggested that DDZ restores the attenuated cardioprotective effect in ovariectomized rat heart, which may be due to downregulation of caveolin and subsequent increase in the activity of eNOS. PMID- 26264743 TI - Tricking the balance: NK cells in anti-cancer immunity. AB - Natural Killer (NK) cells are classically considered innate immune effector cells involved in the first line of defense against infected and malignant cells. More recently, NK cells have emerged to acquire properties of adaptive immunity in response to certain viral infections such as expansion of specific NK cell subsets and long-lasting virus-specific responses to secondary challenges. NK cells distinguish healthy cells from abnormal cells by measuring the net input of activating and inhibitory signals perceived from target cells through NK cell surface receptors. Acquisition of activating ligands in combination with reduced expression of MHC class I molecules on virus-infected and cancer cells activates NK cell cytotoxicity and release of immunostimulatory cytokines like IFN-gamma. In the cancer microenvironment however, NK cells become functionally impaired by inhibitory factors produced by immunosuppressive immune cells and cancer cells. Here we review recent progress on the role of NK cells in cancer immunity. We describe regulatory factors of the tumor microenvironment on NK cell function which determine cancer cell destruction or escape from immune recognition. Finally, recent strategies that focus on exploiting NK cell anti-cancer responses for immunotherapeutic approaches are outlined. PMID- 26264744 TI - Subclass analysis of donor HLA-specific IgG in antibody-incompatible renal transplantation reveals a significant association of IgG4 with rejection and graft failure. AB - Donor HLA-specific antibodies (DSAs) can cause rejection and graft loss after renal transplantation, but their levels measured by the current assays are not fully predictive of outcomes. We investigated whether IgG subclasses of DSA were associated with early rejection and graft failure. DSA levels were determined pretreatment, at the day of peak pan-IgG level and at 30 days post transplantation in eighty HLA antibody-incompatible kidney transplant recipients using a modified microbead assay. Pretreatment IgG4 levels were predictive of acute antibody-mediated rejection (P = 0.003) in the first 30 days post transplant. Pre-treatment presence of IgG4 DSA (P = 0.008) and day 30 IgG3 DSA (P = 0.03) was associated with poor graft survival. Multivariate regression analysis showed that in addition to pan-IgG levels, total IgG4 levels were an independent risk factor for early rejection when measured pretreatment, and the presence of pretreatment IgG4 DSA was also an independent risk factor for graft failure. Pretreatment IgG4 DSA levels correlated independently with higher risk of early rejection episodes and medium-term death-censored graft survival. Thus, pretreatment IgG4 DSA may be used as a biomarker to predict and risk stratify cases with higher levels of pan-IgG DSA in HLA antibody-incompatible transplantation. Further investigations are needed to confirm our results. PMID- 26264745 TI - Regulatory dynamics of network architecture and function in tristable genetic circuit of Leishmania: a mathematical biology approach. AB - The emerging field of synthetic biology has led to the design of tailor-made synthetic circuits for several therapeutic applications. Biological networks can be reprogramed by designing synthetic circuits that modulate the expression of target proteins. IPCS (inositol phosphorylceramide synthase) has been an attractive target in the sphingolipid metabolism of the parasite Leishmania. In this study, we have constructed a tristable circuit for the IPCS protein. The circuit has been validated and its long-term behavior has been assessed. The robustness and evolvability of the circuit has been estimated using evolutionary algorithms. The tristable synthetic circuit has been specifically designed to improve the rate of production of phosphatidylcholine: ceramide cholinephosphotransferase 4 (SLS4 protein). Site-specific delivery of the circuit into the parasite-infected macrophages could serve as a possible therapeutic intervention of the infectious disease 'Leishmaniasis'. PMID- 26264746 TI - Triply cyclometalated trinuclear iridium(III) and trinuclear palladium(II) complexes with a tri-mesoionic carbene ligand. AB - The first example of a triply cyclometalated homopolynuclear tri-Ir(III) complex with additional carbene donors is presented. Cooperative catalysis and the interplay between homogenous and heterogeneous catalyses are discussed for the tri-Ir(III) complex and a related non-cyclometalated tri-Pd(II) complex. PMID- 26264747 TI - A plum-pudding like mesoporous SiO2/flake graphite nanocomposite with superior rate performance for LIB anode materials. AB - A novel kind of plum-pudding like mesoporous SiO2 nanospheres (MSNs) and flake graphite (FG) nanocomposite (pp-MSNs/FG) was designed and fabricated via a facile and cost-effective hydrothermal method. Transmission electron microscopy (TEM) analysis showed that most of the MSNs were well anchored on FG. This special architecture has multiple advantages, including FG that offers a conductive framework and hinders the volume expansion effect. Moreover, the porous structure of MSNs could provide more available lithium storage sites and extra free space to accommodate the mechanical strain caused by the volume change during the repeated reversible reaction between Li(+) and active materials. Due to the synergetic effects of its unique plum-pudding structure, the obtained pp-MSNs/FG nanocomposite exhibited a decent reversible capacity of 702 mA h g(-1) (based on the weight of MSNs in the electrode material) after 100 cycles with high Coulombic efficiency above 99% under 100 mA g(-1) and a charge capacity of 239.6 mA h g(-1) could be obtained even under 5000 mA g(-1). Their high rate performance is among the best-reported performances of SiO2-based anode materials. PMID- 26264749 TI - Preface: Pharmaceutical applications of Raman spectroscopy--From diagnosis to therapeutics. PMID- 26264748 TI - Quantitative analysis reveals how EGFR activation and downregulation are coupled in normal but not in cancer cells. AB - Ubiquitination of the epidermal growth factor receptor (EGFR) that occurs when Cbl and Grb2 bind to three phosphotyrosine residues (pY1045, pY1068 and pY1086) on the receptor displays a sharp threshold effect as a function of EGF concentration. Here we use a simple modelling approach together with experiments to show that the establishment of the threshold requires both the multiplicity of binding sites and cooperative binding of Cbl and Grb2 to the EGFR. While the threshold is remarkably robust, a more sophisticated model predicted that it could be modulated as a function of EGFR levels on the cell surface. We confirmed experimentally that the system has evolved to perform optimally at physiological levels of EGFR. As a consequence, this system displays an intrinsic weakness that causes--at the supraphysiological levels of receptor and/or ligand associated with cancer--uncoupling of the mechanisms leading to signalling through phosphorylation and attenuation through ubiquitination. PMID- 26264751 TI - Effects of two different injury prevention resistance exercise protocols on the hamstring torque-angle relationship: a randomized controlled trial. AB - The effects of two different 6-week lower body injury prevention programmes on knee muscle torque-angle relationship were examined in soccer players. Thirty-two men were randomly assigned to three groups: hamstring-eccentric (ECC) (n = 11), unstable-squatting (UNS) (n = 11), and control (n = 10). Intervention groups performed three training sessions per week using only three ECC or UNS exercises, respectively. Maximal peak knee flexion torque was measured at 35 degrees , 45 degrees , 60 degrees , 80 degrees , 90 degrees , and 100 degrees , pre- and post intervention. Peak torque increased at 35 degrees (P = 0.034, Cohen's d = 0.67) and 45 degrees (P = 0.004, Cohen's d = 0.96) in the ECC group, and at 60 degrees (P = 0.024, Cohen's d = 1.16), 80 degrees (P = 0.018, Cohen's d = 1.21), and 90 degrees (P = 0.001, Cohen's d = 1.38) in the UNS group. As these specific modifications might respectively and differentially protect athletes against hamstring and knee-joint injuries, the integration of both types of exercises should be considered when designing injury prevention programmes for soccer players. PMID- 26264753 TI - Kaposi sarcoma following postmastectomy lymphedema. AB - Classical Kaposi sarcoma (KS) usually appears on lower extremities accompanied or preceded by local lymphedema. However, the development in areas of chronic lymphedema of the arms following mastectomy, mimicking a Stewart-Treves syndrome, has rarely been described. We report an 81-year-old woman who developed multiple, erythematous to purple tumors, located on areas of post mastectomy lymphedema. Histopathological examination evidenced several dermal nodules formed by spindle shaped cells that delimitated slit-like vascular spaces with some red cell extravasation. Immunohistochemically, the human herpesvirus type 8 (HHV-8) latent nuclear antigen-1 was detected in the nuclei of most tumoral cells confirming the diagnosis of KS. Lymphedema could promote the development of certain tumors by altering immunocompetence. Although angiosarcoma (AS) is the most frequent neoplasia arising in the setting of chronic lymphedema, other tumors such as benign lymphangiomatous papules (BLAP) or KS can also develop in lymphedematous limbs. It is important to establish the difference between AS and KS because their prognosis and treatment are very different. Identification by immunohistochemistry of HHV-8 is useful for the distinction between KS and AS or BLAP. PMID- 26264754 TI - Differential detergent sensitivity of extracellular vesicle subpopulations. AB - Extracellular vesicles (including exosomes, microvesicles and apoptotic bodies) are currently attracting rapidly increasing attention from various fields of biology due to their ability to carry complex information and act as autocrine, paracrine and even endocrine intercellular messengers. In the present study we investigated the sensitivity of size-based subpopulations of extracellular vesicles to different concentrations of detergents including sodium dodecyl sulphate, Triton X-100, Tween 20 and deoxycholate. We determined the required detergent concentration that lysed each of the vesicle subpopulations secreted by Jurkat, THP-1, MiaPaCa and U937 human cell lines. We characterized the vesicles by tunable resistive pulse sensing, flow cytometry and transmission electron microscopy. Microvesicles and apoptotic bodies were found to be more sensitive to detergent lysis than exosomes. Furthermore, we found evidence that sodium dodecyl sulphate and Triton X-100 were more effective in vesicle lysis at low concentrations than deoxycholate or Tween 20. Taken together, our data suggest that a combination of differential detergent lysis with tunable resistive pulse sensing or flow cytometry may prove useful for simple and fast differentiation between exosomes and other extracellular vesicle subpopulations as well as between vesicular and non-vesicular structures. PMID- 26264755 TI - Mental and nonmental health hospital admissions among chronically homeless adults before and after supportive housing placement. AB - Individuals experiencing chronic homelessness may utilize hospital services more frequently than the general population. Understanding the benefits of providing permanent supportive housing to these individuals can lead to improved services for this population. This study examined the effect of supportive housing placement on hospital admissions of adults who were homeless. Admissions were examined for a period of one-year pre- and postsupportive housing placement for 23 adults. Results showed a reduction in the number of emergency department admissions and an increase in outpatient admissions during the year following housing placement, indicating that supportive housing may encourage more appropriate use of health care services. PMID- 26264756 TI - Why stigmatize overweight young people as hypertensive by using normative percentiles from non-overweight youth? PMID- 26264757 TI - Serum 25-Hydroxyvitamin D associated with indicators of body fat and insulin resistance in prepubertal chilean children. AB - BACKGROUND: Consistent data on the relation between vitamin D, body fat and insulin resistance (IR) in children are lacking. OBJECTIVES: (1) To evaluate the association between serum 25-Hydroxyvitamin D [25(OH)D] and key indicators of: adiposity (total and central), IR, and (2) to estimate serum 25(OH)D cut-offs that best reflect IR and total and central adiposity in children. SUBJECTS/METHODS: Prepubertal children (n=435, ~53% girls; ~age 7 years) from the Growth and Obesity Chilean Cohort Study were evaluated for potential associations between serum 25(OH)D and indicators of: (1) total adiposity (body mass index by age (BAZ), body fat (including three-component model)), central adiposity (waist circumference and trunk fatness); (2) IR (homeostasis model assessment of IR) and insulin sensitive (quantitative insulin sensitivity check index) using standardized multiple regression models with standardized coefficients and receiver operating characteristic curves. RESULTS: Overall, mean serum 25(OH)D was 32.1+/-9.2 ng ml(-1), while 19.4% of children were obese (BAZ?2 s.d.). Serum 25(OH)D was inversely associated with indicators of total and central adiposity and with IR indicators. Effect sizes were moderate in girls (~0.3 for adiposity and IR indicators), while, weaker values were found in boys. Serum 25(OH)D estimated cut-offs that best predicted total, central adiposity and IR were~30 ng ml(-1). Children with suboptimal serum 25(OH)D (<30 ng ml(-1)) had a higher risk (two to three times) of being obese (high BAZ, body fat percent and/or central adiposity); and three to four times greater risk for IR. CONCLUSIONS: Serum 25(OH)D was inversely associated with adiposity (total and central) and IR indicators in prepubertal Chilean children. The conventional cut-off of vitamin D sufficiency (?30 ng ml(-1)) was adequate to assess obesity and IR risk in this age group. PMID- 26264758 TI - Lipopolysaccharide responsiveness is an independent predictor of death in patients with chronic heart failure. AB - BACKGROUND: The origin of pro-inflammatory activation in chronic heart failure (HF) remains a matter of debate. Lipopolysaccharide (LPS) may enter the blood stream through the morphologically altered and leaky gut barrier. We hypothesized that lower LPS reactivity would be associated with worse survival as compared to normal or higher LPS reactivity. METHODS: LPS responsiveness was studied in 122 patients with chronic HF (mean+/-SD: age 67.3+/-10.3 years, 24 female, New York Heart Association class [NYHA] class: 2.5+/-0.8, left ventricular ejection fraction [LVEF]: 33.5+/-12.5%) and 27 control subjects of similar age (63.7+/-7.7 years, p>0.05). Reference LPS was added at increasing doses to ex vivo whole blood samples and necrosis factor-alpha (TNFalpha) was measured. Patients were subgrouped into good- and poor-responder status according to their potential to react to increasing doses of LPS (delta TNFalpha secretion). The optimal cut-off value was calculated by receiver-operator characteristic curve (ROC) analysis. RESULTS: A total of 56 patients with chronic HF died from any cause during follow up. At 24 months, cumulative mortality was 16.4% (95% confidence interval 16.0 16.7%). The delta TNFalpha value representing the optimal cut-off for the prediction of mortality was 1522 pg/mL (24 months) with a sensitivity of 49.3% (95% confidence interval 37.2-61.4%) and specificity of 81.5% (95% confidence interval 61.9-93.6%). LPS responder status remained an independent predictor of death after multivariable adjustment (hazard ratio 0.09 for good- vs. poor responders, 95% confidence interval 0.01-0.67, p<0.05). CONCLUSIONS: LPS responsiveness in patients with chronic HF is an independent predictor of death. PMID- 26264760 TI - Genetic diversity of Mycoplasma arginini isolates based on multilocus sequence typing. AB - The contribution of Mycoplasma arginini to mycoplasmosis in small ruminants remains unclear because it is recovered from both healthy and diseased animals. In order to gain a better understanding of any relationships between isolates from different sites and different geographical locations, we developed a method for genotyping M. arginini using multilocus sequence typing (MLST). A MLST scheme based on five housekeeping genes was used to characterize M. arginini isolates from flocks of sheep and goats. A high level of genetic variability was detected between strains and within herds. PMID- 26264761 TI - The Histone-Deacetylase-Inhibitor Suberoylanilide Hydroxamic Acid Promotes Dental Pulp Repair Mechanisms Through Modulation of Matrix Metalloproteinase-13 Activity. AB - Direct application of histone-deacetylase-inhibitors (HDACis) to dental pulp cells (DPCs) induces chromatin changes, promoting gene expression and cellular reparative events. We have previously demonstrated that HDACis (valproic acid, trichostatin A) increase mineralization in dental papillae-derived cell-lines and primary DPCs by stimulation of dentinogenic gene expression. Here, we investigated novel genes regulated by the HDACi, suberoylanilide hydroxamic acid (SAHA), to identify new pathways contributing to DPC differentiation. SAHA significantly compromised DPC viability only at relatively high concentrations (5 MUM); while low concentrations (1 MUM) SAHA did not increase apoptosis. HDACi exposure for 24 h induced mineralization-per-cell dose-dependently after 2 weeks; however, constant 14d SAHA-exposure inhibited mineralization. Microarray analysis (24 h and 14 days) of SAHA exposed cultures highlighted that 764 transcripts showed a significant >2.0-fold change at 24 h, which reduced to 36 genes at 14 days. 59% of genes were down-regulated at 24 h and 36% at 14 days, respectively. Pathway analysis indicated SAHA increased expression of members of the matrix metalloproteinase (MMP) family. Furthermore, SAHA-supplementation increased MMP 13 protein expression (7 d, 14 days) and enzyme activity (48 h, 14 days). Selective MMP-13-inhibition (MMP-13i) dose-dependently accelerated mineralization in both SAHA-treated and non-treated cultures. MMP-13i-supplementation promoted expression of several mineralization-associated markers, however, HDACi-induced cell migration and wound healing were impaired. Data demonstrate that short-term low-dose SAHA-exposure promotes mineralization in DPCs by modulating gene pathways and tissue proteases. MMP-13i further increased mineralization associated events, but decreased HDACi cell migration indicating a specific role for MMP-13 in pulpal repair processes. Pharmacological inhibition of HDAC and MMP may provide novel insights into pulpal repair processes with significant translational benefit. J. Cell. Physiol. 231: 798-816, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26264759 TI - Acetylation mediates Cx43 reduction caused by electrical stimulation. AB - Communication between cardiomyocytes depends upon gap junctions (GJ). Previous studies have demonstrated that electrical stimulation induces GJ remodeling and modifies histone acetylase (HAT) and deacetylase (HDAC) activities, although these two results have not been linked. The aim of this work was to establish whether electrical stimulation modulates GJ-mediated cardiac cell-cell communication by acetylation-dependent mechanisms. Field stimulation of HL-1 cardiomyocytes at 0.5 Hz for 24 h significantly reduced connexin43 (Cx43) expression and cell-cell communication. HDAC activity was down-regulated whereas HAT activity was not modified resulting in increased acetylation of Cx43. Consistent with a post-translational mechanism, we did not observe a reduction in Cx43 mRNA in electrically stimulated cells, while the proteasomal inhibitor MG132 maintained Cx43 expression. Further, the treatment of paced cells with the HAT inhibitor Anacardic Acid maintained both the levels of Cx43 and cell-cell communication. Finally, we observed increased acetylation of Cx43 in the left ventricles of dogs subjected to chronic tachypacing as a model of abnormal ventricular activation. In conclusion, our findings suggest that altered electrical activity can regulate cardiomyocyte communication by influencing the acetylation status of Cx43. PMID- 26264762 TI - The irreversibility of sensitive period effects in language development: evidence from second language acquisition in international adoptees. AB - The question of a sensitive period in language acquisition has been subject to extensive research and debate for more than half a century. While it has been well established that the ability to learn new languages declines in early years, the extent to which this outcome depends on biological maturation in contrast to previously acquired knowledge remains disputed. In the present study, we addressed this question by examining phonetic discriminatory abilities in early second language (L2) speakers of Swedish, who had either maintained their first language (L1) (immigrants) or had lost it (international adoptees), using native speaker controls. Through this design, we sought to disentangle the effects of the maturational state of the learner on L2 development from the effects of L1 interference: if additional language development is indeed constrained by an interfering L1, then adoptees should outperform immigrant speakers. The results of an auditory lexical decision task, in which fine vowel distinctions in Swedish had been modified, showed, however, no difference between the L2 groups. Instead, both L2 groups scored significantly lower than the native speaker group. The three groups did not differ in their ability to discriminate non-modified words. These findings demonstrate that L1 loss is not a crucial condition for successfully acquiring an L2, which in turn is taken as support for a maturational constraints view on L2 acquisition. A video abstract of this article can be viewed at: https://youtu.be/1J9X50aePeU. PMID- 26264763 TI - Reflective and Agentive Functions of Narrative Writing: a Qualitative Study on the Narratives of University Students. AB - There is a lively debate in the literature on reflective processes and on the necessity to view them as consisting with differing levels of complexity. Within a semiotic and psychodynamic perspective, we present a conceptualization on reflective processes which distinguishes between reflection and reflectivity and articulates their relationship with narrative devices.The study analyzes 224 narratives of critical events written by 77 underachieving university students that took part in group training courses during the INSTALL European project.The corpus was subjected to a qualitative analysis of narrative function, with the aim of detecting narrative functions of reflection, reflectivity and agency, the latter being considered as an interconnected construct to the reflective process.The functions were discussed both on the basis of how the narrators reacted to the discontinuity in their self-image caused by the critical event, and based upon different types of narrative coherence (chronological, causal, thematic, autobiographical).The results highlighted that narratives with a reflection function, attribute the discontinuity generated by the event to the self, and show a causal coherence; those whose function is reflectivity interpret the discontinuity attributing it to the self in relation to others and present a thematic coherence; those of agency ascribe the discontinuity to a potential selves in action, and are characterized by an autobiographical coherence.The implications of the study will be discussed with reference to the value of narrative writing in promoting reflective-agentive processes. PMID- 26264764 TI - Fear of blood draw and total draw time combine to predict vasovagal reactions among whole blood donors. AB - BACKGROUND: Fear of blood draws is a predictor of vasovagal reaction risk among whole blood donors, and this relationship is particularly evident among less experienced donors. This study examines the combined effect of donor fear and total blood draw time on vasovagal reactions. STUDY DESIGN AND METHODS: After successfully completing the blood donor health screening, 2730 whole blood donors attending high school drives were asked about their fear of having blood drawn. Donor reports of fear versus no fear were combined with total blood draw time to predict phlebotomist ratings of donor vasovagal reactions. RESULTS: Both fear and draw time were significant predictors of vasovagal reactions, with observed reaction rates of 31.2% for fearful donors whose blood draw lasted 10 minutes or more versus 5.0% for nonfearful donors whose draw lasted less than 6 minutes. Binomial regression analyses revealed that fear remained a significant predictor of reaction rates across all blood draw intervals examined (odds ratio, 2.8-4.1; all p < 0.001) and that these effects were maintained after controlling for donor sex, weight, estimated blood volume, pulse rate, and donation status. CONCLUSION: This report shows that both fear and blood draw time increase vasovagal reaction rates, and the two are additive. These findings suggest that fearful donors should be the focus of special attention to reduce their distress before donation as well as careful observation throughout the draw. PMID- 26264765 TI - Balancing Radiation and Contrast Media Dose in Single-Pass Abdominal Multidetector CT: Prospective Evaluation of Image Quality. AB - RATIONALE AND OBJECTIVES: As both contrast and radiation dose affect the quality of CT images, a constant image quality in abdominal contrast-enhanced multidetector computed tomography (CE-MDCT) could be obtained balancing radiation and contrast media dose according to the age of the patients. MATERIALS AND METHODS: Seventy-two (38 Men; 34 women; aged 20-83 years) patients underwent a single-pass abdominal CE-MDCT. Patients were divided into three different age groups: A (20-44 years); B (45-65 years); and C (>65 years). For each group, a different noise index (NI) and contrast media dose (370 mgI/mL) was selected as follows: A (NI, 15; 2.5 mL/kg), B (NI, 12.5; 2 mL/kg), and C (NI, 10; 1.5 mL/kg). Radiation exposure was reported as dose-length product (DLP) in mGy * cm. For quantitative analysis, signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were calculated for both the liver (L) and the abdominal aorta (A). Statistical analysis was performed with a one-way analysis of variance. Standard imaging criteria were used for qualitative analysis. RESULTS: Although peak hepatic enhancement was 152 +/- 16, 128 +/- 12, and 101 +/- 14 Hounsfield units (P < .001) for groups A, B, and C, respectively, no significant differences were observed in the corresponding SNRL with 9.2 +/- 1.4, 9.1 +/- 1.2, and 9.2 +/- 3. Radiation (mGy * cm) and contrast media dose (mL) administered were 476 +/- 147 and 155 +/- 27 for group A, 926 +/- 291 and 130 +/- 16 for group B, and 1981 +/- 451 and 106 +/- 15 for group C, respectively (P < .001). None of the studies was graded as poor or inadequate by both readers, and the prevalence-adjusted bias adjusted kappa ranged between 0.48 and 0.93 for all but one criteria. CONCLUSIONS: A constant image quality in CE-MDCT can be obtained balancing radiation and contrast media dose administered to patients of different age. PMID- 26264766 TI - Exertional Heat Illnesses and Environmental Conditions During High School Football Practices. AB - BACKGROUND: Guidelines for preventing exertional heat illnesses (EHIs) during extreme heat stress should be specific to regional environments, age, and sport and should be based on evidence of reducing the risk. Each year in the United States, over 1 million high school football players practice in the August heat; however, no published data describe the incidence of EHIs in these athletes. PURPOSE: To describe the environmental conditions and incidence of EHIs during high school football practices over a 3-month period. STUDY DESIGN: Descriptive epidemiology study. METHODS: For a 3-month period (August-October), athletic trainers at 12 high schools in North Central Florida recorded the practice time and length, environmental conditions (wet-bulb globe temperature), and incidences of EHIs in varsity football athletes. RESULTS: Athletes suffered 57 total EHIs during 29,759 athlete-exposures (AEs) for the 3-month data collection period (rate = 1.92/1000 AEs). August accounted for the majority of all EHIs, with 82.5% (47/57) and the highest rate (4.35/1000 AEs). Of total heat illnesses, heat cramps accounted for 70.2% (40/57), heat exhaustion 22.8% (13/57), and heat syncope 7.0% (4/57). The odds ratio indicated that athletes in August practices that lasted longer than the recommended 3 hours were 9.84 times more likely to suffer a heat illness than those in practices lasting <=3 hours. CONCLUSION: The highest rate of EHIs was during August. Practices in August that exceeded the recommended 3 hours were associated with a greater risk of heat illnesses. The overall rate of EHIs was lower for the high school football athletes observed in the study compared with that reported for collegiate football athletes in the region. The low rates of EHIs recorded suggest that the prevention guidelines employed by sports medicine teams are appropriate for the region and population. CLINICAL RELEVANCE: Team physicians and athletic trainers should employ evidence based, region- and population-specific EHI prevention guidelines. Sports medicine teams, coaches, and athletes should be aware of the increased risk of EHIs during August practices and the risk of prolonged practices during August. PMID- 26264767 TI - Five-year changes in gait biomechanics after concomitant high tibial osteotomy and ACL reconstruction in patients with medial knee osteoarthritis. AB - BACKGROUND: Concomitant high tibial osteotomy (HTO) and anterior cruciate ligament (ACL) reconstruction is a combined surgical procedure intended to improve kinematics and kinetics in the unstable ACL-deficient knee with varus malalignment and medial compartment knee osteoarthritis (OA). PURPOSE: To investigate 5-year changes in gait biomechanics as well as radiographic and patient-reported outcomes bilaterally after unilateral, concomitant medial opening wedge HTO and ACL reconstruction. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 33 patients (mean +/- SD age, 40 +/- 9 years) with varus malalignment (mean mechanical axis angle, -5.9 degrees +/- 2.9 degrees ), medial compartment knee OA, and ACL deficiency completed 3-dimensional gait analysis preoperatively and 2 and 5 years postoperatively. Primary outcomes were the peak external knee adduction (first peak) and flexion moments. Secondary outcomes were the peak external knee extension and transverse plane moments, peak knee angles in all 3 planes, radiographic static knee alignment measures (mechanical axis angle and posterior tibial slope), and the Knee injury and Osteoarthritis Outcome Score (KOOS). RESULTS: There was a substantial decrease in the knee adduction moment in the surgical limb (%BW * H, -1.49; 95% CI, -1.75 to 1.22) and a slight increase in the nonsurgical limb (%BW * H, 0.16; 95% CI, 0.03 to 0.30) from preoperatively to 5 years postoperatively. There was also a decrease in the knee flexion moment for both the surgical (%BW * H, -0.67; 95% CI, -1.19 to -0.15) and nonsurgical limbs (%BW * H, -1.06; 95% CI, -1.49 to 0.64). Secondary outcomes suggested that substantial improvements were maintained at 5 years, although smaller declines were observed in several measures and in both limbs from 2 to 5 years. CONCLUSION: Changes in the peak external moments about the knee in all 3 planes during walking were observed 5 years after concomitant medial opening wedge HTO and ACL reconstruction. These findings are consistent with an intended, sustained shift in the mediolateral distribution of knee loads. CLINICAL RELEVANCE: These findings suggest that concomitant HTO and ACL reconstruction results in substantial changes in gait biomechanics. Future clinical research comparing treatment strategies is both warranted and required for this relatively uncommon but seemingly biomechanically efficacious procedure. PMID- 26264768 TI - The Interrater and Intrarater Agreement of a Modified Neer Classification System and Associated Treatment Choice for Lateral Clavicle Fractures. AB - BACKGROUND: As there is substantial variation in the classification and diagnosis of lateral clavicle fractures, proper management can be challenging. Although the Neer classification system modified by Craig has been widely used, no study has assessed its validity through inter- and intrarater agreement. PURPOSE: To determine the inter- and intrarater agreement of the modified Neer classification system and associated treatment choice for lateral clavicle fractures and to assess whether 3-dimensional computed tomography (3D CT) improves the level of agreement. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3. METHODS: Nine experienced shoulder specialists and 9 orthopaedic fellows evaluated 52 patients with lateral clavicle fractures, completing fracture typing according to the modified Neer classification system and selecting a treatment choice for each case. Web-based assessment was performed using plain radiographs only, followed by the addition of 3D CT images 2 weeks later. This procedure was repeated 4 weeks later. Fleiss kappa values were calculated to estimate the inter- and intrarater agreement. RESULTS: Based on plain radiographs only, the inter- and intrarater agreement of the modified Neer classification system was regarded as fair (kappa = 0.344) and moderate (kappa = 0.496), respectively; the inter- and intrarater agreement of treatment choice was both regarded as moderate (kappa = 0.465 and 0.555, respectively). Based on the plain radiographs and 3D CT images, the inter- and intrarater agreement of the classification system was regarded as fair (kappa = 0.317) and moderate (kappa = 0.508), respectively; the inter- and intrarater agreement of treatment choice was regarded as moderate (kappa = 0.463) and substantial (kappa = 0.623), respectively. There were no significant differences in the level of agreement between the plain radiographs only and plain radiographs plus 3D CT images for any kappa values (all P > .05). CONCLUSION: The level of interrater agreement of the modified Neer classification system for lateral clavicle fractures was fair. Additional 3D CT did not improve the overall level of interrater or intrarater agreement of the modified Neer classification system or associated treatment choice. To eliminate a common source of disagreement among surgeons, a new classification system to focus on unclassifiable fracture types is needed. PMID- 26264769 TI - Catastrophic Failure of an Acetabular Stress Fracture in a Healthy Male Power Lifter. PMID- 26264770 TI - Knee Kinematics During Noncontact Anterior Cruciate Ligament Injury as Determined From Bone Bruise Location. AB - BACKGROUND: The motions causing noncontact anterior cruciate ligament (ACL) injury remain unclear. Tibiofemoral bone bruises are believed to be the result of joint impact near the time of ACL rupture. The locations and frequencies of these bone bruises have been reported, but there are limited data quantifying knee position and orientation near the time of injury based on these contusions. HYPOTHESIS: Knee position and orientation near the time of noncontact ACL injury include extension and anterior tibial translation. STUDY DESIGN: Descriptive laboratory study. METHODS: Magnetic resonance images of 8 subjects with noncontact ACL injuries were acquired within 1 month of injury and were subsequently analyzed. All subjects exhibited bruises on both the femur and tibia in both medial and lateral compartments. The outer margins of bone and the bone bruise surfaces were outlined on each image to create a 3-dimensional model of each subject's knee in its position during magnetic resonance imaging (MRI position). Numerical optimization was used to maximize overlap of the bone bruises on the femur and tibia and to predict the position of injury. Flexion angle, valgus orientation, internal tibial rotation, and anterior tibial translation were measured in both the MRI position and the predicted position of injury. Differences in kinematics between the MRI position, which served as an unloaded reference, and the predicted position of injury were compared by use of paired t tests. RESULTS: Flexion angle was near full extension in both the MRI position and the predicted position of injury (8 degrees vs 12 degrees ; P = .2). Statistically significant increases in valgus orientation (5 degrees ; P = .003), internal tibial rotation (15 degrees ; P = .003), and anterior tibial translation (22 mm; P < .001) were observed in the predicted position of injury relative to the MRI position. CONCLUSION: These results suggest that for the bone bruise pattern studied, landing on an extended knee is a high risk for ACL injury. Extension was accompanied by increased anterior tibial translation (22 mm), internal tibial rotation (15 degrees ), and valgus rotation (5 degrees ) in the predicted position of injury relative to the MRI position. CLINICAL RELEVANCE: This study provides novel data characterizing the motions associated with ACL injury, information critical to improving strategies aimed at injury prevention. PMID- 26264771 TI - Length Changes of the Anterolateral Ligament During Passive Knee Motion: A Human Cadaveric Study. AB - BACKGROUND: Persistent rotatory instability after anterior cruciate ligament (ACL) reconstruction may be a result of unaddressed insufficiency of the anterolateral structures. Recent publications about the anatomy of the anterolateral ligament (ALL) have led to a renewed interest in lateral extra articular procedures, and several authors have proposed ALL reconstruction to supplement intra-articular ACL reconstruction. However, only limited knowledge about the biomechanical characteristics of the ALL exists. PURPOSE/HYPOTHESIS: The purpose of this study was to analyze length changes of the ALL during passive knee motion. The study hypothesis was that the ALL lengthens with knee flexion and internal tibial rotation. STUDY DESIGN: Controlled laboratory study. METHODS: The ALL of 6 cadaveric knees was dissected. Specimens were mounted in a specifically designed test rig that allowed unconstrained passive flexion/extension movement between 0 degrees and 90 degrees as well as external/internal tibial rotation of 25 degrees at various flexion angles. Highly elastic, capacitive polydimethylsiloxane strain gauges were attached to the insertion sites of the ALL. Length changes were recorded continuously at flexion angles between 0 degrees and 90 degrees and during internal/external tibial rotation at 0 degrees , 15 degrees , 30 degrees , 45 degrees , 60 degrees , 75 degrees , and 90 degrees . All measurements were calculated as the relative length change (%) of the ALL compared with 0 degrees of flexion and neutral rotation. RESULTS: The mean relative length of the ALL significantly increased with increasing knee flexion (P < .001), with an estimated mean length change of +0.15% per degree. Both internal and external tibial rotation were independent determinants for length change; internal rotation significantly increased the length of the ALL (P < .001), whereas external rotation significantly decreased its length (P < .001). The mean length change with internal rotation increased with knee flexion, with a significantly greater length change at 90 degrees compared with 0 degrees (P = .048), 15 degrees (P = .033), and 30 degrees (P = .015). The maximum mean length change was +33.77% +/- 9.62%, which was observed at 25 degrees of internal rotation and 90 degrees of flexion. CONCLUSION: The ALL is a nonisometric structure that tensions with knee flexion and internal tibial rotation. Length changes with internal rotation were greater at higher flexion angles, with the greatest length change of the ALL observed at 90 degrees of flexion. CLINICAL RELEVANCE: The ALL can be considered a stabilizer against internal tibial rotation, especially at deep flexion angles. With regard to ALL reconstruction procedures, tensioning and fixation of the graft should be performed near 90 degrees of flexion because graft tensioning near extension may cause excessive ligament strain with increasing knee flexion. PMID- 26264772 TI - Configuration of the Shoulder Complex During the Arm-Cocking Phase in Baseball Pitching. AB - BACKGROUND: The role of the scapula during high-velocity baseball pitching has been described without 3-dimensional kinematic data. It has been speculated that the scapula functions to align the humerus with the spine of the scapula on both the transverse and scapular planes at the end of the arm-cocking phase. HYPOTHESIS: Two hypotheses were formulated: (1) the scapulothoracic protraction angle correlates with the humerothoracic horizontal adduction angle among participants, and (2) the scapulohumeral rhythm of the humerothoracic elevation is not the same as the normal ratio (2:1) observed widely in controlled abductions. STUDY DESIGN: Descriptive laboratory study. METHODS: A total of 20 Japanese professional baseball pitchers were asked to pitch 3 fastballs as they would normally during pitching practice. The 3-dimensional kinematic data of the thorax, scapulae, humeri, and pelvis were recorded using an electromagnetic tracking device operating at 240 Hz. Humerothoracic, scapulothoracic, and glenohumeral joint configurations were determined at the instant of stride-foot contact (SFC) and the end of the arm-cocking phase (MER). RESULTS: The mean (+/ SD) glenohumeral horizontal adduction (-6 degrees +/- 7 degrees ) and elevation (85 degrees +/- 10 degrees ) angles at the MER indicated that the humerus was positioned almost parallel to the spine of the scapula. The mean scapulothoracic protraction angle (15 degrees +/- 10 degrees ) was significantly correlated with the humerothoracic horizontal adduction angle (10 degrees +/- 11 degrees ) at the MER (r = 0.76, P < .001) but not at the SFC (r = 0.13, P = .58). The scapulohumeral rhythm (4.2 [+/-1.9]:1) expressed as the ratio of the glenohumeral elevation angle to the scapulothoracic upward rotation angle at the MER was significantly greater than the normal ratio (2:1) (P < .01). CONCLUSION: The results supported the hypotheses, providing evidence to corroborate the widely accepted concept that the scapula functions to align the humerus with the spine of the scapula so as to limit the glenohumeral joint configuration within the "safe zone" at the MER. CLINICAL RELEVANCE: Disruption of coordination, such as abnormal patterns including "SICK" scapula (scapular malposition, inferior medial border prominence, coracoid pain, and dyskinesis) and scapular dyskinesis, may result in an abnormal configuration of the glenohumeral joint at the MER. PMID- 26264773 TI - Authentic leadership and thriving among nurses: the mediating role of empathy. AB - AIM: To examine the relationship between perceived authentic leadership and two dimensions of thriving (learning and vitality) among nurses, and to study the mediating role of empathy in this relationship. BACKGROUND: Nurses' thriving is a key asset for health care organisations, and its significant role warrants the need to identify the underlying key determinants and psychological mechanisms. METHOD: A cross-sectional design was carried out in a large hospital in September 2013. Self-administered questionnaires were distributed to 360 nurses. The main hypotheses were tested through hierarchical regression analyses. RESULTS: The significant positive relationship between perceived authentic leadership and vitality was mediated by perceived empathy. This mediation, however, was not confirmed in relation to learning. CONCLUSIONS: Nurse managers' authentic leadership enhances nurses' thriving at work. Furthermore, empathic nurse managers seem to increase the vitality of their nurses. IMPLICATIONS FOR NURSING MANAGEMENT: Training nurse managers in authentic leadership skills is important for the nursing field, as those skills help nurse managers to better express empathy and consequently foster thriving in nursing. PMID- 26264775 TI - Skin cancers detected as casual findings with reflectance confocal microscopy in the assessment of melasma treatment. PMID- 26264774 TI - Protein acetylation dynamics in response to carbon overflow in Escherichia coli. AB - In Escherichia coli, acetylation of proteins at lysines depends largely on a non enzymatic acetyl phosphate-dependent mechanism. To assess the functional significance of this post-translational modification, we first grew wild-type cells in buffered tryptone broth with glucose and monitored acetylation over time by immunochemistry. Most acetylation occurred in stationary phase and paralleled glucose consumption and acetate excretion, which began upon entry into stationary phase. Transcription of rprA, a stationary phase regulator, exhibited similar behavior. To identify sites and substrates with significant acetylation changes, we used label-free, quantitative proteomics to monitor changes in protein acetylation. During growth, both the number of identified sites and the extent of acetylation increased with considerable variation among lysines from the same protein. As glucose-regulated lysine acetylation was predominant in central metabolic pathways and overlapped with acetyl phosphate-regulated acetylation sites, we deleted the major carbon regulator CRP and observed a dramatic loss of acetylation that could be restored by deleting the enzyme that degrades acetyl phosphate. We propose that acetyl phosphate-dependent acetylation is a response to carbon flux that could regulate central metabolism. PMID- 26264776 TI - Discovery of urinary biomarkers of whole grain rye intake in free-living subjects using nontargeted LC-MS metabolite profiling. AB - SCOPE: Whole grain (WG) intake is associated with decreased risk of developing colorectal cancer, type 2 diabetes, and cardiovascular disease and its comorbidities. However, the role of specific grains is unclear. Moreover, intake of specific WG is challenging to measure accurately with traditional dietary assessment methods. Our aim was to use nontargeted metabolite profiling to discover specific urinary biomarkers for WG rye to objectively reflect intake under free-living conditions. METHODS AND RESULTS: WG rye intake was estimated by weighed food records, and 24 h urine collections were analyzed by LC-MS. Multivariate modeling was undertaken by repeated double cross-validated partial least squares regression against reported WG rye intake, which correlated well with multivariate prediction estimates (r = 0.67-0.80, p < 0.001), but not with intakes of WG wheat or oats. Hydroxyhydroxyphenyl acetamide sulfate, 3,5 dihydroxyphenylpropionic acid sulfate, caffeic acid sulfate, and hydroxyphenyl acetamide sulfate were among the 20 features that had the greatest potential as intake biomarkers of WG. In addition, three compounds exhibited MS/MS fragmentation of carnitine structures. CONCLUSION: With this nontargeted approach, we confirmed the specificity of alkylresorcinol metabolites as biomarkers for WG rye intake, but also discovered other compounds that should be evaluated as putative biomarkers in future studies. PMID- 26264777 TI - Magnetic field dependence of spatial frequency encoding NMR as probed on an oligosaccharide. AB - The magnetic field dependence of spatial frequency encoding NMR techniques is addressed through a detailed analysis of (1)H NMR spectra acquired under spatial frequency encoding on an oligomeric saccharide sample. In particular, the influence of the strength of the static magnetic field on spectral and spatial resolutions that are key features of this method is investigated. For this purpose, we report the acquisition of correlation experiments implementing broadband homodecoupling or J-edited spin evolutions, and we discuss the resolution enhancements that are provided by these techniques at two different magnetic fields. We show that performing these experiments at higher field improves the performance of high resolution NMR techniques based on a spatial frequency encoding. The significant resolution enhancements observed on the correlation spectra acquired at very high field make them valuable analytical tools that are suitable for the assignment of (1)H chemical shifts and scalar couplings in molecules with highly crowded spectrum such as carbohydrates. PMID- 26264778 TI - Development of anemia, phlebotomy practices, and blood transfusion requirements in 45 critically ill cats (2009-2011). AB - OBJECTIVE: To describe the incidence of the development of anemia, the number of phlebotomies performed daily, the approximate volume of blood withdrawn, the transfusion requirements and their association with duration of hospitalization and survival to discharge in critically ill cats. DESIGN: Retrospective study from January 2009 to January 2011. SETTING: University teaching hospital. ANIMALS: Cats hospitalized in the intensive care unit (ICU) for >48 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records of cats hospitalized for >48 hours in the ICU were examined. Of the 45 cats included, 60% (27/45) were not anemic upon admission to the ICU. Of these, 74.1% (20/27) developed anemia during their ICU stay. Development of anemia was associated with a longer duration of hospitalization (P = 0.002) but not with survival (P = 0.46). Fourteen cats (31.1%; 14/45) received one or more packed red blood cell transfusions and had significantly longer ICU stays (P < 0.001). Transfusion requirements were not associated with survival (P = 0.66). The median number of phlebotomies per day for all cats in the ICU was 3 (range 1-6). This was significantly associated with the development of anemia (P = 0.0011) and higher transfusion requirements (P = 0.16) in the 14 cats that received a transfusion. The estimated volume phlebotomized was significantly (P < 0.001) greater in cats that required a transfusion (median volume 3.32 mL/kg/ICU stay) compared to cats that did not require a transfusion (median volume 1.11 mL/kg/ICU stay) but was not associated with survival to discharge (P = 0.84). CONCLUSIONS: Development of anemia necessitating blood transfusions is common in critically ill cats and leads to significantly longer duration of ICU hospitalization. Iatrogenic anemia from frequent phlebotomies is an important cause for increased transfusion requirement. Fewer phlebotomies and other blood conserving strategies in these patients may help reduce the incidence of anemia and decrease transfusion requirements, as well as result in shorter hospital stays. PMID- 26264779 TI - Fecal microbiota transplantation in the management of hepatic encephalopathy. PMID- 26264780 TI - Defining end-stage renal disease in clinical trials: a framework for adjudication. AB - Unlike definition of stroke and myocardial infarction, there is no uniformly agreed upon definition to adjudicate end-stage renal disease (ESRD). ESRD remains the most unambiguous and clinically relevant end point for clinical trialists, regulators, payers and patients with chronic kidney disease. The prescription of dialysis to patients with advanced chronic kidney disease is subjective and great variations exist among physicians and countries. Given the difficulties in diagnosing ESRD, the presence of estimated GFR <15 mL/min/1.7 3m(2) itself has been suggested as an end point. However, this definition is still a surrogate since many patients may live years without being symptomatic or needing dialysis. The purpose of this report is to describe a framework to define when the kidney function ends and when ESRD can be adjudicated. Discussed in this report are (i) the importance of diagnosing symptomatic uremia or advanced asymptomatic uremia thus establishing the need for dialysis; (ii) establishing the chronicity of dialysis so as to distinguish it from acute dialysis; (iii) establishing ESRD when dialysis is unavailable, refused or considered futile and (iv) the adjudication process. Several challenges and ambiguities that emerge in clinical trials and their possible solutions are provided. The criteria proposed herein may help to standardize the definition of ESRD and reduce the variability in adjudicating the most important renal end point in clinical trials of chronic kidney disease. PMID- 26264781 TI - Development and validation of a carers quality-of-life questionnaire for parkinsonism (PQoL Carers). AB - PURPOSE: Atypical parkinsonism (AP) has a considerable impact on the lives not only of patients but also of their carers. The aim of this study was to develop an instrument for assessing the quality of life (QoL) of carers of patients with AP. METHODS: A 40-item pool was generated from in-depth interviews with carers of patients with AP, a thorough review of the existing literature and consultation with movement disorder experts. Item refinement and reduction was performed using the results of pilot testing and a survey in 282 carers of multiple system atrophy (MSA) patients and 226 carers of progressive supranuclear palsy (PSP) patients. A validation study, with responses of 243 carers of MSA and 187 carers of PSP patients, was undertaken to evaluate the psychometric properties of the final 26-item scale. RESULTS: The validation study results suggest that the scale is unidimensional and has high internal consistency (Cronbach's alpha = 0.96). The correlations of scale scores with patients' health status and QoL measures, such as PDQ-39 summary score and EQ-5D index (Spearman's rho = 0.56 and -0.31, respectively, P < 0.001), as well as carers' measures, such as Caregiver Burden Inventory (CBI) total and EQ-5D index (Spearman's rho = 0.85 and -0.39, respectively, P < 0.001), document the convergent and concurrent validity of the scale. ANOVA results support the discriminant validity of the scale, as evidenced by its capacity to differentiate between carers with varying levels of self reported health. CONCLUSIONS: The 26-item Parkinsonism Carers QoL (PQoL Carer) is a concise instrument with adequate psychometric qualities that can be used for clinical and research purposes. PMID- 26264783 TI - MultiSETTER: web server for multiple RNA structure comparison. AB - BACKGROUND: Understanding the architecture and function of RNA molecules requires methods for comparing and analyzing their tertiary and quaternary structures. While structural superposition of short RNAs is achievable in a reasonable time, large structures represent much bigger challenge. Therefore, we have developed a fast and accurate algorithm for RNA pairwise structure superposition called SETTER and implemented it in the SETTER web server. However, though biological relationships can be inferred by a pairwise structure alignment, key features preserved by evolution can be identified only from a multiple structure alignment. Thus, we extended the SETTER algorithm to the alignment of multiple RNA structures and developed the MultiSETTER algorithm. RESULTS: In this paper, we present the updated version of the SETTER web server that implements a user friendly interface to the MultiSETTER algorithm. The server accepts RNA structures either as the list of PDB IDs or as user-defined PDB files. After the superposition is computed, structures are visualized in 3D and several reports and statistics are generated. CONCLUSION: To the best of our knowledge, the MultiSETTER web server is the first publicly available tool for a multiple RNA structure alignment. The MultiSETTER server offers the visual inspection of an alignment in 3D space which may reveal structural and functional relationships not captured by other multiple alignment methods based either on a sequence or on secondary structure motifs. PMID- 26264784 TI - Asymmetries in children's production of relative clauses: data from English and Korean. AB - We report here on a series of elicited production experiments that investigate the production of indirect object and oblique relative clauses by monolingual child learners of English and Korean. Taken together, the results from the two languages point toward a pair of robust asymmetries: children manifest a preference for subject relative clauses over indirect object relative clauses, and for direct object relative clauses over oblique relative clauses. We consider various possible explanations for these preferences, of which the most promising seems to involve the requirement that the referent of the head noun be easily construed as what the relative clause is about. PMID- 26264785 TI - The Accordant Trend of Both Parameters (rgs Expression and cAMP Content) Follows the Pattern of Development of Fruiting Body in Volvariella volvacea. AB - The formation of fruiting body in Volvariella volvacea is affected by endogenous genes and environmental factors. However, its regulation at a molecular level is still poorly understood. To study the genes involved in the formation of fruiting body, we cloned a new regulator of the G protein signaling (RGS) encoding gene (rgs) from V. volvacea. Phylogenetic analysis showed that RGS in V. volvacea and other basidiomycete RGS proteins from Schizophyllum commune and Coprinus cinereus belong to the same clade. In addition, we assayed intracellular cAMP content in the three developmental stages (mycelium, fruiting body primordia, and button). We also found that the expression of rgs was highly positively correlated to the content of intracellular cAMP during fruiting body formation. The conserved protein sequences and expression of rgs, together with high concent of cAMP at primordia tissue, suggested that rgs gene and cAMP may play a crucial role in fruiting body formation in V. volvacea. PMID- 26264786 TI - Ultrasmall microdisk and microring lasers based on InAs/InGaAs/GaAs quantum dots. AB - Ultrasmall microring and microdisk lasers with an asymmetric air/GaAs/Al0.98Ga0.02As waveguide and an active region based on InAs/InGaAs/GaAs quantum dots emitting around 1.3 MUm were fabricated and studied. The diameter D of the microrings and microdisks was either 2 or 1.5 MUm, and the inner diameter d of the microrings varied from 20% to 70% of the outer diameter D. The microring with D = 2 MUm and d = 0.8 MUm demonstrated a threshold pump power as low as 1.8 MUW at room temperature. Lasing was observed up to 100 degrees C owing to the use of quantum dots providing high confinement energy both for electrons and holes. Tuning spectral positions of the whispering gallery modes via changing the inner diameters of the microrings was demonstrated. PACS: 78.67.Hc; 42.55.Sa; 42.50.Pq; 78.55.Cr. PMID- 26264787 TI - Mindfulness in cultural context. AB - Mindfulness meditation and other techniques drawn from Buddhism have increasingly been integrated into forms of psychotherapeutic intervention. In much of this work, mindfulness is understood as a mode of awareness that is present-centered and nonevaluative. This form of awareness is assumed to have intrinsic value in promoting positive mental health and adaptation by interrupting discursive thoughts that give rise to suffering. However, in the societies where it originated, mindfulness meditation is part of a larger system of Buddhist belief and practice with strong ethical and moral dimensions. Extracting techniques like mindfulness meditation from the social contexts in which they originate may change the nature and effects of the practice. The papers in this issue of Transcultural Psychiatry explore the implications of a cultural and contextual view of mindfulness for continued dialogue between Buddhist thought and psychiatry. This introductory essay considers the meanings of mindfulness meditation in cultural context and the uses of mindfulness as a therapeutic intervention in contemporary psychiatry and psychology. PMID- 26264788 TI - Ready-JET-Go: Split Flow Accelerates ED Throughput. AB - PROBLEM: Struggling to keep up with The Centers for Medicare and Medicaid Services out-patient throughput metrics, an adult emergency department serving Burlington and Camden Counties, New Jersey, sought to redefine its care delivery model by adopting the patient segmentation initiatives of the split-flow process of patient care. METHODS: A multidisciplinary team of ED clinicians collaboratively defined the patient segmentation criteria. A joint assessment team approach to patient care was instituted. A 3-pronged approach was adopted to prepare staff for the patient care changes in line with an existing framework specified by the Institute of Medicine. Simulation and queuing analyses were used to estimate the accompanying resource needs. RESULTS: Since implementing split flow, the emergency department has witnessed significant improvements in patient throughput and patient satisfaction, despite a sustained 10% increase in patient volumes after split-flow implementation. The median length of stay for discharged patients and the door-to-diagnostic evaluation time are now down to 112 minutes and 30 minutes, respectively, compared with pre-split-flow values of 192 minutes and 72 minutes, respectively. IMPLICATIONS FOR PRACTICE: Working collaboratively with all stakeholders to define the right patient care delivery model, combined with an understanding of the right resource assignments to optimally support that care delivery model, an emergency department can institute cost-effective changes to realize and sustain significant patient throughput improvements. PMID- 26264789 TI - The determinants of bond angle variability in protein/peptide backbones: A comprehensive statistical/quantum mechanics analysis. AB - The elucidation of the mutual influence between peptide bond geometry and local conformation has important implications for protein structure refinement, validation, and prediction. To gain insights into the structural determinants and the energetic contributions associated with protein/peptide backbone plasticity, we here report an extensive analysis of the variability of the peptide bond angles by combining statistical analyses of protein structures and quantum mechanics calculations on small model peptide systems. Our analyses demonstrate that all the backbone bond angles strongly depend on the peptide conformation and unveil the existence of regular trends as function of psi and/or phi. The excellent agreement of the quantum mechanics calculations with the statistical surveys of protein structures validates the computational scheme here employed and demonstrates that the valence geometry of protein/peptide backbone is primarily dictated by local interactions. Notably, for the first time we show that the position of the H(alpha) hydrogen atom, which is an important parameter in NMR structural studies, is also dependent on the local conformation. Most of the trends observed may be satisfactorily explained by invoking steric repulsive interactions; in some specific cases the valence bond variability is also influenced by hydrogen-bond like interactions. Moreover, we can provide a reliable estimate of the energies involved in the interplay between geometry and conformations. PMID- 26264791 TI - Investigations of the presence of caffeine in the Rudawa River, Krakow, Poland. AB - Caffeine concentration in surface water (Rudawa River, Krakow, Poland) has been being investigated since 2011. The method applied for investigations was developed in 2011, and the first series of measurements of caffeine concentration in surface water began in 2011. Caffeine concentration was determined by the gas chromatography-mass spectrometry (GC-MS) method. Solid phase extraction (SPE) was used to enrich the concentration of caffeine in water samples. As an internal standard, the caffeine isotope (13)C3 in methanol (Sigma Aldrich) was used. The values of four additional parameters (concentration of nitrates, biochemical oxygen demand after 7 days, number of Escherichia coli and number of Enterococcus faecalis) were determined for the water sample analyzed. Caffeine was detected in all studied samples. The control series of measurements during 2011-2014 confirmed that caffeine is present in Rudawa River water and that the concentration of this substance in Rudawa River ranges from 14.0 to 852.0 ng/dm(3). There is no correlation between the concentration of caffeine and the concentration of other anthropogenic contaminants determined in water. PMID- 26264790 TI - How does your kidney smell? Emerging roles for olfactory receptors in renal function. AB - Olfactory receptors (ORs) are chemosensors that are responsible for one's sense of smell. In addition to this specialized role in the nose, recent evidence suggests that ORs are also found in a variety of additional tissues including the kidney. As this list of renal ORs continues to expand, it is becoming clear that they play important roles in renal and whole-body physiology, including a novel role in blood pressure regulation. In this review, we highlight important considerations that are crucial when studying ORs and present the current literature on renal ORs and their emerging relevance in maintaining renal function. PMID- 26264792 TI - Effects of food on pharmacokinetics of immediate release oral formulations of simple analgesics: potential implications for drug use, safety and efficacy. PMID- 26264793 TI - The Placenta--An Undervalued Miracle. PMID- 26264795 TI - Helping Women Understand Treatment Options for Vulvar and Vaginal Atrophy. AB - Vulvar and vaginal atrophy (VVA) is a common and progressive medical condition in postmenopausal women. The REVIVE (REal Women's VIews of Treatment Options for Menopausal Vaginal ChangEs) survey assessed knowledge about VVA and its impact in 3,046 postmenopausal U.S. women, and recorded women's attitudes about their interactions with health care providers and about available treatments. REVIVE identified poor disease awareness and understanding among women, failure of health care professionals to evaluate women for VVA signs and symptoms, low treatment rates and concerns about the safety and efficacy of available therapies. Strategies to address these needs include proactive screening, education for women and clinicians about VVA and recommendations for treatment and follow-up. PMID- 26264796 TI - Implications of Using Pulse Oximetry to Screen for Critical Congenital Heart Disease in Newborns. AB - In recent years, pulse oximetry screening for critical congenital heart disease (CCHD) in newborns has been added to the list of recommended uniform screening panels and recommended by several health care organizations. Most states use pulse oximetry to screen for CCHD. Studies have identified problems with compliance and higher failure rate at moderate altitudes than at sea level, suggesting the need for alternate algorithms. Altitude, time, health status of newborns and type of cardiac defect appear to affect results. Early detection of CCHD improves health outcomes and reduces morbidity and mortality. Barriers to screening include out-of-hospital births, cost and knowledge deficits among health care professionals. PMID- 26264797 TI - Prevention, Treatment and Parent Education for Diaper Dermatitis. AB - Diaper dermatitis is a common cutaneous condition characterized by an acute inflammatory eruption of the skin in the diaper area of an infant. Although this condition is relatively common, it can cause considerable pain and stress for infants and can be troublesome for their caregivers. In the United States, the frequency of diaper dermatitis is substantial and accounts for a high number of visits to health care providers. The three most common types of diaper dermatitis are chafing dermatitis, irritant contact dermatitis and diaper candidiasis. This article reviews common causes, differential diagnosis, current prevention and treatment recommendations, nursing implications and practical tips for families to utilize while caring for their infants at home. PMID- 26264798 TI - Latest Evidence on Alcohol and Pregnancy. AB - Alcohol increases risk for miscarriage, birth defects and other problems, and it is the sole cause of the range of physical, developmental and cognitive problems known as fetal alcohol spectrum disorders (FASD), which can affect up to 5 percent of all pregnancies. Many women report drinking early in pregnancy, often before they know they're pregnant. When knowledgeable of the latest research evidence, nurses can counsel women of the risks alcohol use poses to a healthy pregnancy. PMID- 26264799 TI - Serotonin Syndrome in Pregnancy. AB - Millions of people take selective serotonin reuptake inhibitors (SSRIs) for depression and anxiety, so nurses and other clinicians need to be aware of the potential for serotonin toxicity and serotonin syndrome. These conditions can occur when women taking SSRIs are given additional medications in the labor and birth or postpartum settings. Symptoms can have an acute onset and can include delirium, fever and hypertension. Understanding the mechanism and symptoms of serotonin syndrome can lead to timely treatment of this unusual condition. PMID- 26264800 TI - A Primer for Nurses on Perinatal/Neonatal Stroke. AB - Perinatal or neonatal stroke is not uncommon, but diagnosis is often missed. Perinatal nurses are often the first health professionals in the position to observe the most typical symptom of stroke in a newborn, which is focal seizure. Etiology, symptoms and outcomes are reviewed and discussed through the context of the author's personal story. PMID- 26264801 TI - Hospital Safety for Women With Nicotine Addiction. AB - Hospital smoke-free policies are expanding to include all hospital-owned land and property. Because some women will choose to leave the hospital to satisfy nicotine cravings, smoke-free policies should account for this. Components of a policy can include a carefully designed smoking waiver form, nicotine substitution, smoking cessation education, behavioral counseling and supervised transport of women who choose to leave the hospital to smoke. Education of women and their families, awareness by all staff, and clearly defined guidelines can lead to improved safety. PMID- 26264802 TI - HPV9 Vaccine for the Prevention of Human Papillomavirus-Related Cancers. AB - Human papillomavirus (HPV) is the most common sexually transmitted infection (STI) in the United States, with approximately 79 million Americans currently infected. Persistent infection with HPV has been identified as the causative factor in the development of invasive cervical cancer as well as other oral and genital cancers in women and men. The quadravalent HPV4 vaccine has been available since 2006. In December 2014, the U.S. Food and Drug Administration (FDA) approved the HPV9 vaccine that provides coverage for five additional oncogenic strains of HPV that are not included in the first generation vaccine. PMID- 26264803 TI - New Clinical Protocol on Breastfeeding and Substance Abuse. PMID- 26264804 TI - Help Put an End to Diaper Need. PMID- 26264805 TI - Birth Intuition. PMID- 26264807 TI - Knowing When to Be "Rational": Flexible Economic Decision Making and Executive Function in Preschool Children. AB - Failure to delay gratification may not indicate poor control or irrationality, but might be an adaptive response. Two studies investigated 3.5- and 4.5-year-old children's ability to adapt their delay and saving behavior when their preference (e.g., to delay or not delay) became nonadaptive. In Study 1 (N = 140), children's delay preference was associated with a risk of losing rewards. In Study 2 (N = 142), children's saving preference was associated with an inability to play an attractive game. Whereas baseline delaying and saving preferences were unrelated to a standardized executive function measure, children who switched to their nonpreferred choice scored higher, suggesting flexibility of decision making may be a more meaningful dependent variable than baseline performance in developmental research on self-control. PMID- 26264806 TI - Dorzolamide synergizes the antitumor activity of mitomycin C against Ehrlich's carcinoma grown in mice: role of thioredoxin-interacting protein. AB - The antitumor activity of carbonic anhydrase (CA) inhibitors is attributed to their ability to induce a state of intracellular acidification. In fact, acidic intracellular pH was demonstrated to upregulate several tumor suppressor proteins and increase the activity of many chemotherapies. The present study aimed to investigate the antitumor activity of the CA inhibitor, dorzolamide, in combination with mitomycin C and to study the effect of these drugs on tumoral thioredoxin-interacting protein (TXNIP) as well as tumor cell proliferation and apoptosis. Solid tumors were induced by subcutaneous inoculation of Ehrlich's ascites carcinoma (EAC) cells in female mice. Mice were treated with dorzolamide (3, 10, or 30 mg/kg/day, i.p.) and/or mitomycin C (1 mg/kg, i.p.) weekly for 3 weeks. Treatment with mitomycin C increased TXNIP level in EAC solid tumors in mice. Likewise, treatment with dorzolamide upregulated TXNIP and p53 while downregulated bcl-2. Both drug therapies increased tumoral caspase 9, caspase 3, and PARP-1 cleavage in addition to decreasing the proliferative Ki-67-stained nuclear fraction. Indeed, a synergistic effect was detected between mitomycin C and dorzolamide. The current data demonstrated that the antitumor activity of mitomycin C and dorzolamide was, at least in part, mediated through stimulating tumoral expression of TXNIP and enhancing tumor apoptosis. PMID- 26264808 TI - Helping Couples Fulfill the "Highest of Life's Goals": Mate Selection, Marriage Counselling, and Genetic Counseling in United States. AB - This article traces the history of modern genetic counseling to mate selection and marriage counselling practices of the early-20th century. Mate selection revolved around a belief that human heredity could be improved and genetic diseases eradicated through better breeding. Marriage counselling, though interested in reproduction, was also concerned with the emotional and psychological well-being of couples. These two practices coalesced most obviously in the work of well-known geneticist Sheldon Reed. Even as marriage and genetic counselling diverged in the post-WWII period, vestiges of these practices remain in contemporary counseling experiences with family planning and genetic screening programs. Emphasizing points of continuity between "positive" eugenic ideologies and modern genetic practices elaborates the diverse origins of genetic counseling. It also exposes how genetic counselors have become involved in genetic enterprises beyond standard clinical settings, and prods at key issues in the interaction between genetic science and social values. PMID- 26264810 TI - Identification of key genes associated with the effect of estrogen on ovarian cancer using microarray analysis. AB - PURPOSE: To identify key genes related to the effect of estrogen on ovarian cancer. METHODS: Microarray data (GSE22600) were downloaded from Gene Expression Omnibus. Eight estrogen and seven placebo treatment samples were obtained using a 2 * 2 factorial designs, which contained 2 cell lines (PEO4 and 2008) and 2 treatments (estrogen and placebo). Differentially expressed genes were identified by Bayesian methods, and the genes with P < 0.05 and |log2FC (fold change)| >=0.5 were chosen as cut-off criterion. Differentially co-expressed genes (DCGs) and differentially regulated genes (DRGs) were, respectively, identified by DCe function and DRsort function in DCGL package. Topological structure analysis was performed on the important transcriptional factors (TFs) and genes in transcriptional regulatory network using tYNA. Functional enrichment analysis was, respectively, performed for DEGs and the important genes using Gene Ontology and KEGG databases. RESULTS: In total, 465 DEGs were identified. Functional enrichment analysis of DEGs indicated that ACVR2B, LTBP1, BMP7 and MYC involved in TGF-beta signaling pathway. The 2285 DCG pairs and 357 DRGs were identified. Topological structure analysis showed that 52 important TFs and 65 important genes were identified. Functional enrichment analysis of the important genes showed that TP53 and MLH1 participated in DNA damage response and the genes (ACVR2B, LTBP1, BMP7 and MYC) involved in TGF-beta signaling pathway. CONCLUSION: TP53, MLH1, ACVR2B, LTBP1 and BMP7 might participate in the pathogenesis of ovarian cancer. PMID- 26264809 TI - Drug-releasing mesenchymal cells strongly suppress B16 lung metastasis in a syngeneic murine model. AB - BACKGROUND: Mesenchymal stromal cells (MSCs) are considered an important therapeutic tool in cancer therapy. They possess intrinsic therapeutic potential and can also be in vitro manipulated and engineered to produce therapeutic molecules that can be delivered to the site of diseases, through their capacity to home pathological tissues. We have recently demonstrated that MSCs, upon in vitro priming with anti-cancer drug, become drug-releasing mesenchymal cells (Dr MCs) able to strongly inhibit cancer cells growth. METHODS: Murine mesenchymal stromal cells were loaded with Paclitaxel (Dr-MCsPTX) according to a standardized procedure and their ability to inhibit the growth of a murine B16 melanoma was verified by in vitro assays. The anti-metastatic activity of Dr-MCsPTX was then studied in mice injected i.v. with B16 melanoma cells that produced lung metastatic nodules. Lung nodules were counted under a dissecting stereomicroscope and metastasis investigated by histological analysis. RESULTS: We found that three i.v. injections of Dr-MCsPTX on day 5, 10 and 15 after tumor injection almost completely abolished B16 lung metastasis. Dr-MCsPTX arrested into lung by interacting with endothelium and migrate toward cancer nodule through a complex mechanism involving primarily mouse lung stromal cells (mL-StCs) and SDF 1/CXCR4/CXCR7 axis. CONCLUSIONS: Our results show for the first time that Dr MCsPTX are very effective to inhibit lung metastasis formation. Actually, a cure for lung metastasis in humans is mostly unlikely and we do not know whether a therapy combining engineered MSCs and Dr-MCs may work synergistically. However, we think that our approach using Dr-MCs loaded with PTX may represent a new valid and additive therapeutic tool to fight lung metastases and, perhaps, primary lung cancers in human. PMID- 26264811 TI - Effect of Tween 40 and DtsR1 on L-arginine overproduction in Corynebacterium crenatum. AB - BACKGROUND: L-Glutamate is an important precursor in the L-arginine (L-Arg) biosynthetic pathway. Various methods, including polyoxyethylene sorbitan monopalmitate (Tween 40) addition and dtsR1 disruption, have been widely used to induce L-glutamate overproduction in Corynebacterium glutamicum. In this study, a novel strategy for L-Arg overproduction through Tween 40 trigger and DeltadtsR1 mutant were proposed in Corynebacterium crenatum. RESULTS: Corynebacterium crenatum mutant (CCM01) was selected as a host strain, whose argR was lethal via mutagenesis screening, the proB gene was knocked out, and argB was replaced by argB M4 (E19R, H26E, D311R, and D312R) to release L-Arg feedback resistance. After Tween 40 trigger in the logarithmic period, L-Arg production increased from 15.22 to 17.73 g/L in CCM01 strain. When NCgl1221 and dtsR1 disruption (CCM03), L Arg production drastically increased to 27.45 g/L and then further to 29.97 g/L after Tween 40 trigger. Moreover, the specific activity of alpha-oxoglutarate dehydrogenase complex (ODHC) decreased, whereas the regeneration of NADP(+)/NADPH significantly increased after dtsR1 disruption and Tween 40 trigger. Results of real-time PCR showed that the transcriptional levels of odhA, sucB, and lpdA (encoding three subunits of the ODHC complex) were downregulated after Tween 40 trigger or dtsR1 disruption. By contrast, zwf transcription (encoding glucose-6 phosphate dehydrogenase) showed no significant difference among CCM01, CCM02 (DeltaNCgl1221), and CCM03 (DeltaNCgl1221DeltadtsR1) strains without Tween 40 trigger but evidently increased by 5.50 folds after Tween 40 trigger. CONCLUSION: A novel strategy for L-Arg overproduction by dtsR1 disruption and Tween 40 trigger in C. crenatum was reported. Tween 40 addition exhibited a bifunctional mechanism for L-Arg overproduction, including reduced ODHC activity and enhanced NADPH pools accumulation by downregulated dtsR1 expression and upregulated zwf expression, respectively. PMID- 26264812 TI - Insulin-based strategies to prevent hypoglycaemia during and after exercise in adult patients with type 1 diabetes on pump therapy: the DIABRASPORT randomized study. AB - AIMS: To validate strategies to prevent exercise-induced hypoglycaemia via insulin-dose adjustment in adult patients with type 1 diabetes (T1D) on pump therapy. METHODS: A total of 20 patients randomly performed four 30-min late post lunch (3 h after lunch) exercise sessions and a rest session: two moderate sessions [50% maximum oxygen consumption (VO2 max)] with 50 or 80% basal rate (BR) reduction during exercise + 2 h and two intense sessions (75% VO2 max) with 80% BR reduction or with their pump stopped. Two additional early post-lunch sessions (90 min after lunch) were analysed to compare hypoglycaemia incidence for BR reduction versus bolus reduction. RESULTS: In all, 100 late post-lunch sessions were analysed. Regardless of exercise type and BR reduction, no more hypoglycaemic events occurred in the period until the next morning than occurred after the rest sessions. In the afternoon, no more hypoglycaemic events occurred with 80% BR reduction/moderate exercise or with pump discontinuation/intense exercise than for the rest session, whereas more hypoglycaemic events occurred with 50% BR reduction/moderate exercise and 80% BR reduction/intense exercise. After early post-lunch exercise (n = 37), a trend towards fewer hypoglycaemic episodes was observed with bolus reduction versus BR reduction (p = 0.07). Mean blood glucose fell by ~3.3 mmol/l after 30 min of exercise, irrespective of dose reduction, remaining stable until the next morning with no rebound hyperglycaemia. CONCLUSION: In adults with T1D, to limit the hypoglycaemic risk associated with 30 min of exercise 3 h after lunch, without carbohydrate supplements, the best options seem to be to reduce BR by 80% or to stop the pump for moderate or intense exercise, or for moderate exercise 90 min after lunch, to reduce the prandial bolus rather than the BR. PMID- 26264814 TI - Endothelial Changes in Individuals with Prehypertension. AB - INTRODUCTION: Prehypertension is considered a precursor of systemic arterial hypertension and a predictor of morbidity-mortality due to cardiovascular diseases, which are the main causes of death in Brazil and the world. Thus, early diagnosis and the adoption of therapeutic measures in cases of prehypertension can reduce cardiovascular risk. The aim of the present study was to perform a selective review of the literature to identify and discuss early endothelial changes in individuals with pre-hypertension. RESULTS AND DISCUSSION: The findings indicate an increase in ET-1-mediated vasoconstrictor tone in prehypertension, with endothelial-dependent vasodilatation impairment. Moreover, significantly high levels of angiotensin, arginine and vasopressin were found in this group of patients. A reduction in endothelial fibrinolytic capacity was another important change found in patients with prehypertention and was associated with an increased risk for atherothrombotic events. CONCLUSION: The present findings demonstrate endothelial changes in individuals with prehypertension that contribute to the development of arterial hypertension as well as a high risk for cardiovascular events, underscoring the importance of the early adoption of optimized therapeutic measures for this population. PMID- 26264813 TI - T1 mapping and T2 mapping at 3T for quantifying the area-at-risk in reperfused STEMI patients. AB - BACKGROUND: Whether T1-mapping cardiovascular magnetic resonance (CMR) can accurately quantify the area-at-risk (AAR) as delineated by T2 mapping and assess myocardial salvage at 3T in reperfused ST-segment elevation myocardial infarction (STEMI) patients is not known and was investigated in this study. METHODS: 18 STEMI patients underwent CMR at 3T (Siemens Bio-graph mMR) at a median of 5 (4-6) days post primary percutaneous coronary intervention using native T1 (MOLLI) and T2 mapping (WIP #699; Siemens Healthcare, UK). Matching short-axis T1 and T2 maps covering the entire left ventricle (LV) were assessed by two independent observers using manual, Otsu and 2 standard deviation thresholds. Inter- and intra-observer variability, correlation and agreement between the T1 and T2 mapping techniques on a per-slice and per patient basis were assessed. RESULTS: A total of 125 matching T1 and T2 mapping short-axis slices were available for analysis from 18 patients. The acquisition times were identical for the T1 maps and T2 maps. 18 slices were excluded due to suboptimal image quality. Both mapping sequences were equally prone to susceptibility artifacts in the lateral wall and were equally likely to be affected by microvascular obstruction requiring manual correction. The Otsu thresholding technique performed best in terms of inter- and intra-observer variability for both T1 and T2 mapping CMR. The mean myocardial infarct size was 18.8 +/- 9.4 % of the LV. There was no difference in either the mean AAR (32.3 +/- 11.5 % of the LV versus 31.6 +/- 11.2 % of the LV, P = 0.25) or myocardial salvage index (0.40 +/- 0.26 versus 0.39 +/- 0.27, P = 0.20) between the T1 and T2 mapping techniques. On a per-slice analysis, there was an excellent correlation between T1 mapping and T2 mapping in the quantification of the AAR with an R(2) of 0.95 (P < 0.001), with no bias (mean +/- 2SD: bias 0.0 +/- 9.6 %). On a per-patient analysis, the correlation and agreement remained excellent with no bias (R(2) 0.95, P < 0.0001, bias 0.7 +/ 5.1 %). CONCLUSIONS: T1 mapping CMR at 3T performed as well as T2 mapping in quantifying the AAR and assessing myocardial salvage in reperfused STEMI patients, thereby providing an alternative CMR measure of the the AAR. PMID- 26264815 TI - How to Investigate the Vascular Changes in Resistant Hypertension. AB - The pathophysiological mechanism of resistant hypertension (RH) is related to increased vascular smooth muscle tone and blood volume, exacerbation of the activity of the sympathetic system and hyperactivity of the renin-angiotensin aldosterone system (RAAS), all of which are important regulatory mechanisms of blood pressure. Hypertension is associated with reduced endothelial homeostasis, and thus the best treatment would not only reduce blood pressure but also reverse endothelial injury. RH is associated with more serious vascular dysfunction, assessed by endothelium-dependent vasodilation and the presence of serum biomarkers. Arterial stiffness also constitutes an important independent factor that can determine risk of cardiovascular events in patients with RH; it is an important indicator of vascular changes, and is associated with cardiovascular mortality. Arterial stiffness can be assessed by 3 measures: central blood pressure, augmentation index (AIx) and pulse wave velocity (PWV). PWV is a recognized as main marker of the severity of vascular injury. The increase in central blood pressure caused by backward (reflected) waves can be evaluated as an index derived from an analysis of the central aortic blood pressure curve known as the AIx, and depends on the magnitude and time of the reflected waves and indirectly on heart frequency and arterial stiffness. The evaluation of patients with RH is focused on the identification of causes of hypertension guided by the clinical features of hypertension and metabolic, vascular, endocrine and family history. PMID- 26264817 TI - Shame, guilt, and facial emotion processing: initial evidence for a positive relationship between guilt-proneness and facial emotion recognition ability. AB - Shame and guilt are closely related self-conscious emotions of negative affect that give rise to divergent self-regulatory and motivational behaviours. While guilt-proneness has demonstrated positive relationships with self-report measures of empathy and adaptive interpersonal functioning, shame-proneness tends to be unrelated or inversely related to empathy and is associated with interpersonal difficulties. At present, no research has examined relationships between shame and guilt-proneness with facial emotion recognition ability. Participants (N = 363) completed measures of shame and guilt-proneness along with a facial emotion recognition task which assessed the ability to identify displays of anger, sadness, happiness, fear, disgust, and shame. Guilt-proneness was consistently positively associated with facial emotion recognition ability. In contrast, shame proneness was unrelated to capacity for facial emotion recognition. Findings provide support for theory arguing that guilt and empathy operate synergistically and may also help explain the inverse relationship between guilt-proneness and propensity for aggressive behaviour. PMID- 26264816 TI - Treatment Considerations of Clinical Physician on Hypertension Management in Asia. AB - BACKGROUND: There are important differences in the lifestyle and cardiovascular disease risks between Asian and Western populations. The objective of this survey was to investigate the awareness of these factors in the practice of hypertension management among Asian physicians. METHODS: General practitioners and specialists in Asia were surveyed by questionnaire with regard to their management of hypertension. Physicians attending international conferences or meetings on hypertension between March and May 2014 were asked to participate. RESULTS: In their treatment of hypertensive patients, 87% of the 133 respondents said they considered the Asian lifestyle and region-specific characteristics of hypertension in their treatment decisions, while just less than 11% did not. Almost all physicians (92%) recognized the necessity for an Asian-specific guideline for the management of hypertension. For patients with diabetes, 37% and 59% of the respondents used target systolic blood pressure (SBP) levels of 140 mmHg and 130 mmHg, respectively; for elderly patients, 37% and 53% of respondents used target SBP levels of 140 and l50 mmHg, respectively. Forty-eight percent of Asian physicians used calcium channel blockers as the first-line choice of antihypertensive drug while 34% selected angiotensin II receptor blockers, 14% angiotensin converting enzyme inhibitors and 3% diuretics. CONCLUSION: Asian physicians consider that an Asian-specific guideline is needed for hypertension management in the Asian population. PMID- 26264818 TI - Positive selection of digestive Cys proteases in herbivorous Coleoptera. AB - Positive selection is thought to contribute to the functional diversification of insect-inducible protease inhibitors in plants in response to selective pressures exerted by the digestive proteases of their herbivorous enemies. Here we assessed whether a reciprocal evolutionary process takes place on the insect side, and whether ingestion of a positively selected plant inhibitor may translate into a measurable rebalancing of midgut proteases in vivo. Midgut Cys proteases of herbivorous Coleoptera, including the major pest Colorado potato beetle (Leptinotarsa decemlineata), were first compared using a codon-based evolutionary model to look for the occurrence of hypervariable, positively selected amino acid sites among the tested sequences. Hypervariable sites were found, distributed within -or close to- amino acid regions interacting with Cys-type inhibitors of the plant cystatin protein family. A close examination of L. decemlineata sequences indicated a link between their assignment to protease functional families and amino acid identity at positively selected sites. A function diversifying role for positive selection was further suggested empirically by in vitro protease assays and a shotgun proteomic analysis of L. decemlineata Cys proteases showing a differential rebalancing of protease functional family complements in larvae fed single variants of a model cystatin mutated at positively selected amino acid sites. These data confirm overall the occurrence of hypervariable, positively selected amino acid sites in herbivorous Coleoptera digestive Cys proteases. They also support the idea of an adaptive role for positive selection, useful to generate functionally diverse proteases in insect herbivores ingesting functionally diverse, rapidly evolving dietary cystatins. PMID- 26264819 TI - Molecular characterization and first report of Cryptosporidium genotypes in human population in the Slovak Republic. AB - In our study, we examined 91 fecal samples from five different groups of people containing HIV patients, hemodialysis patients, kidney transplant recipients, immunocompetent humans without clinical signs, and humans with suspected cryptosporidiosis. The purpose of our study was to determine species and genotype composition of representatives of Cryptosporidium spp. using PCR analysis of small subunit ribosomal RNA gene and 60-kDa glycoprotein gene and examine their phylogenetic relationship. In HIV-positive/AIDS-infected group of patients and in hemodialysis patients, no presence of Cryptosporidium species was detected. In two kidney transplant recipients, we detected species/genotypes Cryptosporidium parvum IIaA13G1T1R1 (KT355488) and Cryptosporidium hominis IaA11G2R8 (KT355489) and in two immunocompetent patients with clinical symptoms, we identified Cryptosporidium muris and C. hominis IbA10G2T1 (KT355490). In the group of healthy immunocompetent individuals without clinical signs, we identified species/genotype C. hominis IbA11G2 (KT355491) in one sample. PMID- 26264821 TI - The challenge of post-operative peritonitis after gastrointestinal surgery. AB - Post-operative peritonitis (PP) is a life-threatening hospital-acquired intra abdominal infection with high rates of mortality. Diffuse PP remains a challenge for surgeons. Prognosis and outcome of patients are directly related to early diagnosis and prompt intervention. The diagnosis of PP may be difficult because there are no specific clinical signs and laboratory tests to reject or confirm the diagnosis. Atypical clinical features may be responsible for a delay in reoperation. An early diagnosis and prompt treatment is crucial to prevent the development of organ failure and improve the outcome of the patients with PP. The cornerstones in the management of patients with PP are early hemodynamic support, prompt source control and adequate antimicrobial therapy. PMID- 26264820 TI - A Neuroanatomical Signature for Schizophrenia Across Different Ethnic Groups. AB - Schizophrenia is a disabling clinical syndrome found across the world. While the incidence and clinical expression of this illness are strongly influenced by ethnic factors, it is unclear whether patients from different ethnicities show distinct brain deficits. In this multicentre study, we used structural Magnetic Resonance Imaging to investigate neuroanatomy in 126 patients with first episode schizophrenia who came from 4 ethnically distinct cohorts (White Caucasians, African-Caribbeans, Japanese, and Chinese). Each patient was individually matched with a healthy control of the same ethnicity, gender, and age (+/-1 year). We report a reduction in the gray matter volume of the right anterior insula in patients relative to controls (P < .05 corrected); this reduction was detected in all 4 ethnic groups despite differences in psychopathology, exposure to antipsychotic medication and image acquisition sequence. This finding provides evidence for a neuroanatomical signature of schizophrenia expressed above and beyond ethnic variations in incidence and clinical expression. In light of the existing literature, implicating the right anterior insula in bipolar disorder, depression, addiction, obsessive-compulsive disorder, and anxiety, we speculate that the neuroanatomical deficit reported here may represent a transdiagnostic feature of Axis I disorders. PMID- 26264822 TI - Reply: To PMID 25979617. PMID- 26264824 TI - Severe intrahepatic cholestasis of pregnancy is a risk factor for preeclampsia in singleton and twin pregnancies. PMID- 26264825 TI - Factors that affect duration of untreated illness in pregnant women with bipolar disorder. PMID- 26264826 TI - Singleton birthweight by gestational age following in vitro fertilization in the United States. AB - BACKGROUND: Assisted reproductive technology has been reported to account for a disproportionate higher number of low birthweight infants, even in singleton births. Low birthweight infants occur from preterm birth, decreased intrauterine growth, or both. It is unclear whether infants conceived by in vitro fertilization (IVF) have a reduced intrauterine growth rate or intrauterine growth restriction. Growth-restricted newborns have higher perinatal morbidity and are at increased risk for adult-onset illnesses. To date, there are no national standards for birthweight percentiles by gestational week, allowing for fetal growth assessment of singletons conceived by assisted reproductive technology in the United States. OBJECTIVE: The objective of the study was to establish US singleton IVF reference standards using birthweight percentiles by gestational age for singleton live births resulting from IVF in the United States. STUDY DESIGN: We studied birthweight by completed weeks of gestation for 93,443 singleton IVF births reported to the Society for Assisted Reproductive Technologies, 2006-2010. The third to 97th birthweight percentiles per completed week of gestation for weeks between 24 and 42 were calculated and were compared with recently published birthweight percentiles by gestational age for 3,812,730 US singleton births in 2011. RESULTS: Smoothed birthweight for gestational age charts and curves were created for all US IVF singletons and female-male singletons from 24 to 42 weeks. Over the span of 31-41 weeks of gestation, the 10th, 50th, and 90th birthweight percentile values of IVF singletons were comparable with recently published birthweight percentile values of US singletons. At 40 completed weeks of gestation, the 10th, 50th, and 90th birthweight percentiles of all IVF singletons were 3078, 3506, and 4053 g, as compared with corresponding 3005, 3499, and 4057 g of US singletons. The 10th, 50th, and 90th birthweight percentile values for female and male IVF singletons were also comparable with US female and male singletons. CONCLUSION: Birthweight percentiles per completed week of gestation of IVF and US singletons are approximately equal from 31 until 41 completed weeks, suggesting that intrauterine growth is not reduced in IVF singleton infants. PMID- 26264827 TI - Simulation-Based Learning as a Tactic for Teaching Evidence-Based Practice. AB - This column shares the best evidence-based strategies and innovative ideas on how to facilitate the learning of EBP principles and processes by clinicians as well as nursing and interprofessional students. Guidelines for submission are available at http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1741-6787. PMID- 26264823 TI - Vaginal progesterone, but not 17alpha-hydroxyprogesterone caproate, has antiinflammatory effects at the murine maternal-fetal interface. AB - OBJECTIVE: Progestogen (vaginal progesterone or 17-alpha-hydroxyprogesterone caproate [17OHP-C]) administration to patients at risk for preterm delivery is widely used for the prevention of preterm birth (PTB). The mechanisms by which these agents prevent PTB are poorly understood. Progestogens have immunomodulatory functions; therefore, we investigated the local effects of vaginal progesterone and 17OHP-C on adaptive and innate immune cells implicated in the process of parturition. STUDY DESIGN: Pregnant C57BL/6 mice received vaginal progesterone (1 mg per 200 MUL, n = 10) or Replens (control, 200 MUL, n = 10) from 13 to 17 days postcoitum (dpc) or were subcutaneously injected with 17OHP-C (2 mg per 100 MUL, n = 10) or castor oil (control, 100 MUL, n = 10) on 13, 15, and 17 dpc. Decidual and myometrial leukocytes were isolated prior to term delivery (18.5 dpc) for immunophenotyping by flow cytometry. Cervical tissue samples were collected to determine matrix metalloproteinase (MMP)-9 activity by in situ zymography and visualization of collagen content by Masson's trichrome staining. Plasma concentrations of progesterone, estradiol, and cytokines (interferon [IFN]gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-10, IL 12p70, keratinocyte-activated chemokine/growth-related oncogene, and tumor necrosis factor-alpha) were quantified by enzyme-linked immunosorbent assays. Pregnant mice pretreated with vaginal progesterone or Replens were injected with 10 MUg of an endotoxin on 16.5 dpc (n = 10 each) and monitored via infrared camera until delivery to determine the effect of vaginal progesterone on the rate of PTB. RESULTS: The following results were found: (1) vaginal progesterone, but not 17OHP-C, increased the proportion of decidual CD4+ regulatory T cells; (2) vaginal progesterone, but not 17OHP-C, decreased the proportion of decidual CD8+CD25+Foxp3+ T cells and macrophages; (3) vaginal progesterone did not result in M1->M2 macrophage polarization but reduced the proportion of myometrial IFNgamma+ neutrophils and cervical active MMP-9-positive neutrophils and monocytes; (4) 17OHP-C did not reduce the proportion of myometrial IFNgamma+ neutrophils; however, it increased the abundance of cervical active MMP-9 positive neutrophils and monocytes; (5) vaginal progesterone immune effects were associated with reduced systemic concentrations of IL-1beta but not with alterations in progesterone or estradiol concentrations; and (6) vaginal progesterone pretreatment protected against endotoxin-induced PTB (effect size 50%, P = 0.011). CONCLUSION: Vaginal progesterone, but not 17OHP-C, has local antiinflammatory effects at the maternal-fetal interface and the cervix and protects against endotoxin-induced PTB. PMID- 26264828 TI - Ventilator-associated Pneumonia caused by commensal oropharyngeal Flora; [corrected] a retrospective Analysis of a prospectively collected Database. AB - BACKGROUND: The significance of commensal oropharyngeal flora (COF) as a potential cause of ventilator-associated pneumonia (VAP) is scarcely investigated and consequently unknown. Therefore, the aim of this study was to explore whether COF may cause VAP. METHODS: Retrospective clinical, microbiological and radiographic analysis of all prospectively collected suspected VAP cases in which bronchoalveolar lavage fluid exclusively yielded >= 10(4) cfu/ml COF during a 9.5 year period. Characteristics of 899 recent intensive care unit (ICU) admissions were used as a reference population. RESULTS: Out of the prospectively collected database containing 159 VAP cases, 23 patients were included. In these patients, VAP developed after a median of 8 days of mechanical ventilation. The patients faced a prolonged total ICU length of stay (35 days [P < .001]), hospital length of stay (45 days [P = .001]), and a trend to higher mortality (39 % vs. 26 %, [P = .158]; standardized mortality ratio 1.26 vs. 0.77, [P = .137]) compared to the reference population. After clinical, microbiological and radiographic analysis, COF was the most likely cause of respiratory deterioration in 15 patients (9.4 % of all VAP cases) and a possible cause in 2 patients. CONCLUSION: Commensal oropharyngeal flora appears to be a potential cause of VAP in limited numbers of ICU patients as is probably associated with an increased length of stay in both ICU and hospital. As COF-VAP develops late in the course of ICU admission, it is possibly associated with the immunocompromised status of ICU patients. PMID- 26264829 TI - Surgical approach to hysterectomy for benign gynaecological disease. AB - BACKGROUND: The four approaches to hysterectomy for benign disease are abdominal hysterectomy (AH), vaginal hysterectomy (VH), laparoscopic hysterectomy (LH) and robotic-assisted hysterectomy (RH). OBJECTIVES: To assess the effectiveness and safety of different surgical approaches to hysterectomy for women with benign gynaecological conditions. SEARCH METHODS: We searched the following databases (from inception to 14 August 2014) using the Ovid platform: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; Cumulative Index to Nursing and Allied Health Literature (CINAHL) and PsycINFO. We also searched relevant citation lists. We used both indexed and free-text terms. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in which clinical outcomes were compared between one surgical approach to hysterectomy and another. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected trials, assessed risk of bias and performed data extraction. Our primary outcomes were return to normal activities, satisfaction, quality of life, intraoperative visceral injury and major long-term complications (i.e. fistula, pelvi-abdominal pain, urinary dysfunction, bowel dysfunction, pelvic floor condition and sexual dysfunction). MAIN RESULTS: We included 47 studies with 5102 women. The evidence for most comparisons was of low or moderate quality. The main limitations were poor reporting and imprecision. Vaginal hysterectomy (VH) versus abdominal hysterectomy (AH) (nine RCTs, 762 women)Return to normal activities was shorter in the VH group (mean difference (MD) -9.5 days, 95% confidence interval (CI) 12.6 to -6.4, three RCTs, 176 women, I(2) = 75%, moderate quality evidence). There was no evidence of a difference between the groups for the other primary outcomes. Laparoscopic hysterectomy (LH) versus AH (25 RCTs, 2983 women)Return to normal activities was shorter in the LH group (MD -13.6 days, 95% CI -15.4 to 11.8; six RCTs, 520 women, I(2) = 71%, low quality evidence), but there were more urinary tract injuries in the LH group (odds ratio (OR) 2.4, 95% CI 1.2 to 4.8, 13 RCTs, 2140 women, I(2) = 0%, low quality evidence). There was no evidence of a difference between the groups for the other primary outcomes. LH versus VH (16 RCTs, 1440 women)There was no evidence of a difference between the groups for any primary outcomes. Robotic-assisted hysterectomy (RH) versus LH (two RCTs, 152 women)There was no evidence of a difference between the groups for any primary outcomes. Neither of the studies reported satisfaction rates or quality of life.Overall, the number of adverse events was low in the included studies. AUTHORS' CONCLUSIONS: Among women undergoing hysterectomy for benign disease, VH appears to be superior to LH and AH, as it is associated with faster return to normal activities. When technically feasible, VH should be performed in preference to AH because of more rapid recovery and fewer febrile episodes postoperatively. Where VH is not possible, LH has some advantages over AH (including more rapid recovery and fewer febrile episodes and wound or abdominal wall infections), but these are offset by a longer operating time. No advantages of LH over VH could be found; LH had a longer operation time, and total laparoscopic hysterectomy (TLH) had more urinary tract injuries. Of the three subcategories of LH, there are more RCT data for laparoscopic-assisted vaginal hysterectomy and LH than for TLH. Single-port laparoscopic hysterectomy and RH should either be abandoned or further evaluated since there is a lack of evidence of any benefit over conventional LH. Overall, the evidence in this review has to be interpreted with caution as adverse event rates were low, resulting in low power for these comparisons. The surgical approach to hysterectomy should be discussed and decided in the light of the relative benefits and hazards. These benefits and hazards seem to be dependent on surgical expertise and this may influence the decision. In conclusion, when VH is not feasible, LH may avoid the need for AH, but LH is associated with more urinary tract injuries. There is no evidence that RH is of benefit in this population. Preferably, the surgical approach to hysterectomy should be decided by the woman in discussion with her surgeon. PMID- 26264830 TI - Characterization of Brassica napus Flavonol Synthase Involved in Flavonol Biosynthesis in Brassica napus L. AB - Recently, Brassica napus has become a very important crop for plant oil production. Flavonols, an uncolored flavonoid subclass, have a high antioxidative effect and are known to have antiproliferative, antiangiogenic, and neuropharmacological properties. In B. napus, some flavonoid structural genes have been identified, such as, BnF3H-1, BnCHS, and BnC4H-1. However, no studies on FLS genes in B. napus have been conducted. Thus, in this study, we cloned and characterized the function of BnFLS gene B. napus. By overexpression of the BnFLS gene, flavonol (kaempferol and quercetin) levels were recovered in the Arabidopsis atfls1-ko mutant. In addition, we found that the higher endogenous flavonol levels of BnFLS-ox in vitro shoots correlated with slightly higher ROS scavenging activities. Thus, our results indicate that the BnFLS gene encodes for a BnFLS enzyme that can be manipulated to specifically increase flavonol accumulation in oilseed plants and other species such as Arabidopsis. PMID- 26264831 TI - Polyethylenimine-coated SPION exhibits potential intrinsic anti-metastatic properties inhibiting migration and invasion of pancreatic tumor cells. AB - Due to its aggressive behavior, pancreatic cancer is one of the principal causes of cancer-related deaths. The highly metastatic potential of pancreatic tumor cells demands the development of more effective anti-metastatic approaches for this disease. Although polyethylenimine-coated superparamagnetic iron oxide nanoparticles (PEI-coated SPIONs) have been studied for their utility as transfection agents, little is known of their effect on tumor cell biology. Here we demonstrated that PEI-coated SPIONs have potent inhibitory effects on pancreatic tumor cell migration/invasion, through inhibition of Src kinase and decreased expression of MT1-MMP and MMP2 metalloproteinases. When treated with PEI-coated SPIONs, the pancreatic tumor cell line Pan02 showed reduced invadosome density and thus, a decrease in their ability to invade through basement membrane. These nanoparticles temporarily downmodulated microRNA-21, thereby upregulating the cell migration inhibitors PTEN, PDCD4 and Sprouty-1. PEI-coated SPIONs thus show intrinsic, possibly anti-metastatic properties for modulating pancreatic tumor cell migration machinery, which indicates their potential as anti-metastatic agents for treatment of pancreatic cancer. PMID- 26264832 TI - Multifunctional liposomes having target specificity, temperature-triggered release, and near-infrared fluorescence imaging for tumor-specific chemotherapy. AB - We designed functional liposomes with target specificity, temperature-triggered drug release, and near-infrared fluorescence imaging. We prepared the liposomes by triple functionalization of stable pegylated liposomes with thermosensitive poly[2-(2-ethoxy)ethoxyethyl vinyl ether] chains (lower critical solution temperature around 38 degrees C) with conjugation of antibody trastuzumab (Herceptin, HER), which targets human epidermal growth factor 2, and with incorporation of indocyanine green for near-infrared fluorescence imaging. The liposomes retained DOX in the interior below physiological temperature but released DOX immediately at temperatures higher than 40 degrees C. The liposomes exhibited excellent ability for association and internalization to target cells overexpressing Her-2, such as SK-OV3 and SB-BR3 cells, and killed these cells when heated at 45 degrees C for 5 min. When administered intravenously to mice bearing SK-OV3 tumor, the liposomes having HER accumulated in the tumor more efficiently than the liposomes without HER. They stayed there more than 48 h, as judged with near-infrared fluorescence imaging. Furthermore, when the tumor sites of the mice being administered with the DOX-loaded liposomes were heated mildly at 44 degrees C for 10 min at 7h after administration, tumor growth was suppressed strongly thereafter. Treatment with the HER-conjugated liposomes produced more efficient tumor-suppressive effects. Results demonstrate that the synergy of target-specific association, temperature-triggered drug release, and imaging is important for efficient tumor chemotherapy. PMID- 26264834 TI - The scope and sequence of growth factor delivery for vascularized bone tissue regeneration. AB - Bone regeneration is a complex process, that in vivo, requires the highly coordinated presentation of biochemical cues to promote the various stages of angiogenesis and osteogenesis. Taking inspiration from the natural healing process, a wide variety of growth factors are currently being released within next generation tissue engineered scaffolds (in a variety of ways) in order to heal non-union fractures and bone defects. This review will focus on the delivery of multiple growth factors to the bone regeneration niche, specifically 1) dual growth factor delivery signaling and crosstalk, 2) the importance of growth factor timing and temporal separation, and 3) the engineering of delivery systems that allow for temporal control over presentation of soluble growth factors. Alternative methods for growth factor presentation, including the use of gene therapy and platelet-rich plasma scaffolds, are also discussed. PMID- 26264833 TI - Controlled release strategies for modulating immune responses to promote tissue regeneration. AB - Advances in the field of tissue engineering have enhanced the potential of regenerative medicine, yet the efficacy of these strategies remains incomplete, and is limited by the innate and adaptive immune responses. The immune response associated with injury or disease combined with that mounted to biomaterials, transplanted cells, proteins, and gene therapies vectors can contribute to the inability to fully restore tissue function. Blocking immune responses such as with anti-inflammatory or immunosuppressive agents are either ineffective, as the immune response contributes significantly to regeneration, or have significant side effects. This review describes targeted strategies to modulate the immune response in order to limit tissue damage following injury, promote an anti inflammatory environment that leads to regeneration, and induce antigen (Ag) specific tolerance that can target degenerative diseases that destroy tissues and promote engraftment of transplanted cells. Focusing on targeted immuno modulation, we describe local delivery techniques to sites of inflammation as well as systemic approaches that preferentially target subsets of immune populations. PMID- 26264835 TI - Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes. AB - In recent years, in vitro transcribed messenger RNA (mRNA) has emerged as a potential therapeutic platform. To fulfill its promise, effective delivery of mRNA to specific cell types and tissues needs to be achieved. Lipid nanoparticles (LNPs) are efficient carriers for short-interfering RNAs and have entered clinical trials. However, little is known about the potential of LNPs to deliver mRNA. Here, we generated mRNA-LNPs by incorporating HPLC purified, 1 methylpseudouridine-containing mRNA comprising codon-optimized firefly luciferase into stable LNPs. Mice were injected with 0.005-0.250mg/kg doses of mRNA-LNPs by 6 different routes and high levels of protein translation could be measured using in vivo imaging. Subcutaneous, intramuscular and intradermal injection of the LNP encapsulated mRNA translated locally at the site of injection for up to 10days. For several days, high levels of protein production could be achieved in the lung from the intratracheal administration of mRNA. Intravenous and intraperitoneal and to a lesser extent intramuscular and intratracheal deliveries led to trafficking of mRNA-LNPs systemically resulting in active translation of the mRNA in the liver for 1-4 days. Our results demonstrate that LNPs are appropriate carriers for mRNA in vivo and have the potential to become valuable tools for delivering mRNA encoding therapeutic proteins. PMID- 26264837 TI - Acute inhalation of vaporized nicotine increases arterial pressure in young non smokers: a pilot study. AB - PURPOSE: Electronic cigarettes are growing in popularity, but the physiological consequences of vaporized nicotine are unknown. METHODS: Twenty healthy non smokers inhaled vaporized nicotine and placebo (randomized). RESULTS: Nicotine inhalation was associated with higher arterial pressures in the seated position, and increased arterial pressures in the head-up positions with no other effects on autonomic control. CONCLUSIONS: Our results show that vaporized nicotine inhalation is not innocuous. Longitudinal studies in otherwise healthy non smokers should be conducted. PMID- 26264838 TI - A walking disaster: a case of incomplete spinal cord injury with symptomatic orthostatic hypotension. AB - Eight months post-injury, an ambulatory 58-year-old male with an incomplete spinal cord injury experienced syncope and a 52-mmHg drop in his systolic blood pressure during a tilt-table assessment. This case study highlights the necessity to examine autonomic function in all cases of spinal cord injury, regardless of injury severity. PMID- 26264836 TI - Multistage vector (MSV) therapeutics. AB - One of the greatest challenges in the field of medicine is obtaining controlled distribution of systemically administered therapeutic agents within the body. Indeed, biological barriers such as physical compartmentalization, pressure gradients, and excretion pathways adversely affect localized delivery of drugs to pathological tissue. The diverse nature of these barriers requires the use of multifunctional drug delivery vehicles that can overcome a wide range of sequential obstacles. In this review, we explore the role of multifunctionality in nanomedicine by primarily focusing on multistage vectors (MSVs). The MSV is an example of a promising therapeutic platform that incorporates several components, including a microparticle, nanoparticles, and small molecules. In particular, these components are activated in a sequential manner in order to successively address transport barriers. PMID- 26264839 TI - Antimalarial benzoheterocyclic 4-aminoquinolines: Structure-activity relationship, in vivo evaluation, mechanistic and bioactivation studies. AB - A novel class of benzoheterocyclic analogues of amodiaquine designed to avoid toxic reactive metabolite formation was synthesized and evaluated for antiplasmodial activity against K1 (multidrug resistant) and NF54 (sensitive) strains of the malaria parasite Plasmodium falciparum. Structure-activity relationship studies led to the identification of highly promising analogues, the most potent of which had IC50s in the nanomolar range against both strains. The compounds further demonstrated good in vitro microsomal metabolic stability while those subjected to in vivo pharmacokinetic studies had desirable pharmacokinetic profiles. In vivo antimalarial efficacy in Plasmodium berghei infected mice was evaluated for four compounds, all of which showed good activity following oral administration. In particular, compound 19 completely cured treated mice at a low multiple dose of 4*10mg/kg. Mechanistic and bioactivation studies suggest hemozoin formation inhibition and a low likelihood of forming quinone-imine reactive metabolites, respectively. PMID- 26264840 TI - Exploring new Probenecid-based carbonic anhydrase inhibitors: Synthesis, biological evaluation and docking studies. AB - Novel Probenecid-based amide derivatives, incorporating different natural amino acids, were synthesized and assayed to test their effect on the human carbonic anhydrase (hCA, EC 4.2.1.1) transmembrane isoforms hCA IX and XII over the ubiquitous isoforms hCA I and II. Most of them presented a complete loss of hCA II inhibition (K(i)s > 10,000 nM) and strong inhibitory activity against hCA IX and XII in the nanomolar range with respect to the parent compound. A residual activity against hCA I was observed for some of them. These biological results have been explained by docking studies within the active sites of the four studied human carbonic anhydrases (with or without the zinc-bound water) and helped us to better comprehend the rationale behind the design of tertiary sulfonamide compounds as potent but atypical inhibitors of specific isoforms of human carbonic anhydrase. PMID- 26264841 TI - Molecular dynamics and density functional studies on the metabolic selectivity of antipsychotic thioridazine by cytochrome P450 2D6: Connection with crystallographic and metabolic results. AB - CYP2D6, a cytochrome P450 isoform, significantly contributes to the metabolism of many clinically important drugs. Thioridazine (THD) is one of the phenothiazine type antipsychotics, which exhibit dopamine D2 antagonistic activity. THD shows characteristic metabolic profiles compared to other phenothiazine-type antipsychotics such as chlorpromazine. The sulfur atom attached to the phenothiazine ring is preferentially oxidized mainly by CYP2D6, that is, the 2 sulfoxide is a major metabolite, and interestingly this metabolite shows more potent activity against dopamine D2 receptors than THD. On the other hand, the formation of this metabolite causes many serious problems for its clinical use. Wojcikowski et al. (Drug Metab. Dispos. 2006, 34, 471) reported a kinetic study of THD formed by CYP2D6. Recently, Wang et al. (J. Biol. Chem. 2012, 287, 10834 and J. Biol. Chem. 2015, 290, 5092) revealed the crystallographic structure of THD with CYP2D6. In the current study, the binding and reaction mechanisms at the atomic and electronic levels were computationally examined based on the assumption as to whether or not the different crystallographic binding poses correspond to the different metabolites. The binding and oxidative reaction steps in the whole metabolic process were investigated using molecular dynamics and density functional theory calculations, respectively. The current study demonstrated the essential importance of the orientation of the substrate in the reaction center of CYP2D6 for the metabolic reaction. PMID- 26264842 TI - A new small molecule inhibitor of soluble guanylate cyclase. AB - Soluble guanylate cyclase (sGC) is a haem containing enzyme that regulates cardiovascular homeostasis and multiple mechanisms in the central and peripheral nervous system. Commonly used inhibitors of sGC activity act through oxidation of the haem moiety, however they also bind haemoglobin and this limits their bioavailability for in vivo studies. We have discovered a new class of small molecule inhibitors of sGC and have characterised a compound designated D12 (compound 10) which binds to the catalytic domain of the enzyme with a KD of 11 MUM in a SPR assay. PMID- 26264843 TI - Photoaffinity labeling studies of the carbohydrate-binding proteins with different affinities. AB - Photoaffinity labeling has been used as a promising approach to detection and isolation of carbohydrate-binding proteins, which are typically characterized by low binding affinity and selectivity. When there are several specific binding proteins, it is desirable that a photoaffinity probe is capable of simultaneously crosslinking them and that the crosslinking yields depend on the relative binding affinities. In this study, we describe the design and synthesis of carbohydrate photoaffinity probes and their ability to capture lectins of different binding affinities. PMID- 26264844 TI - Phosphate-modified analogues of m(7)GTP and m(7)Gppppm(7)G-Synthesis and biochemical properties. AB - The synthesis and biochemical properties of 17 new mRNA cap analogues are reported. Six of these nucleotides are m(7)GTP derivatives, whereas 11 are 'two headed' tetraphosphate dinucleotides based on a m(7)Gppppm(7)G structure. The compounds contain either a boranophosphate or phosphorothioate moiety in the nucleoside neighbouring position(s) and some of them possess an additional methylene group between beta and gamma phosphorus atoms. The compounds were prepared by divalent metal chloride-mediated coupling of an appropriate m(7)GMP analogue with a given P(1),P(2)-di(1-imidazolyl) derivative. The analogues were evaluated as tools for studying cap-dependent processes in a number of biochemical assays, including determination of affinity to eukaryotic initiation factor eIF4E, susceptibility to enzymatic hydrolysis, and translational efficiency in vitro. The results indicate that modification in the phosphate chain can increase binding to cap-interacting proteins and provides higher resistance to degradation. Furthermore, modified derivatives of m(7)GTP were found to be potent inhibitors of cap-dependent translation in cell free systems. PMID- 26264845 TI - Design and synthesis of dithiocarbamate linked beta-carboline derivatives: DNA topoisomerase II inhibition with DNA binding and apoptosis inducing ability. AB - A series of new beta-carboline-dithiocarbamate derivatives bearing phenyl, dithiocarbamate and H/methyl substitutions at position-1, 3 and 9, respectively, were designed and synthesized. These derivatives 8a-l and 13a-l and their starting precursors (7 a-d and 12 a-d) have been evaluated for their in vitro cytotoxic activity on selected human cancer cell lines. Among the derivatives tested, 7 c, 12 c, 8 a, 8 d, 8 i, 8 j, 8 k, 8l and 13 d-l exhibited considerable cytotoxicity against most of the tested cancer cell lines (IC50<10MUM). Interestingly, most of the derivatives (8 a-l and 13a-l) exhibited enhanced activity than their precursors (7 a-d and 12 a-d), which indicates that the combination of dithiocarbamate with beta-carboline enhances the cytotoxicity of 8 a-l and 13 a-l. Moreover, the derivatives 8 j and 13 g exhibited significant cytotoxic activity with IC50 values of 1.34 MUM and 0.79 MUM on DU-145 cancer cells, respectively. Further, the induction of apoptosis by these derivatives was confirmed by Annexin V-FITC and Hoechst staining assays. However, both biophysical as well as molecular docking studies suggested a combilexin-type of interaction between these derivatives and DNA, unlike simple beta-carbolines. With a view to understand their mechanism of action, DNA topoisomerase II (topo II) inhibition assay was also performed. Overall, the present study emphasizes the importance of linking a dithiocarbamate moiety to the beta-carboline scaffold for exhibiting profound activity. PMID- 26264846 TI - Evaluation of transition-state mimics in a superior BACE1 cleavage sequence as peptide-mimetic BACE1 inhibitors. AB - A superior substrate sequence for BACE1 containing transition-state mimics at the scissile site was evaluated as a protease inhibitor. Hydroxymethylcarbonyl (HMC) and hydroxyethylamine (HEA) isosteres were selected as the transition state mimics, and incorporated into the scissile site of the superior sequence covering the P4 to P1' sites (Glu-Ile-Thi-Thi(*)Nva; (*)denotes the cleavage site). Isosteres having different absolute configurations of the hydroxyl group were synthesized separately, and the effect of the configuration was evaluated. Configuration of the hydroxyl group of each isostere showed a marked effect on the inhibitory activity; anti-configuration to the scissile site substituent had potent inhibitory activity in an HMC-type inhibitor, whereas anti-configuration of HEA-type inhibitors showed no inhibitory activity. Structural evaluations based on X-ray crystallographic analyses of recombinant BACE1 in complex with each inhibitor provided insights into the protein-ligand interactions, especially at the prime sites. PMID- 26264847 TI - Ribosome-targeting antibiotics as inhibitors of oncogenic microRNAs biogenesis: Old scaffolds for new perspectives in RNA targeting. AB - MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression at the post transcriptional level. It is now well established that the overexpression of some miRNAs (oncogenic miRNAs) is responsible for initiation and progression of human cancers and the discovery of new molecules able to interfere with their production and/or function represents one of the most important challenges of current medicinal chemistry of RNA ligands. In this work, we studied the ability of 18 different antibiotics, known as prokaryotic ribosomal RNA, to bind to oncogenic miRNA precursors (stem-loop structured pre-miRNAs) in order to inhibit miRNAs production. In vitro inhibition, binding constants, thermodynamic parameters and binding sites were investigated and highlighted that aminoglycosides and tetracyclines represent interesting pre-miRNA ligands with the ability to inhibit Dicer processing. PMID- 26264848 TI - The use of cardiovascular imaging in prognostic stratification. PMID- 26264849 TI - What is the effect of fasting on the lifespan of neurons? AB - Medical advancements have increased life expectancy but have consequently increased the incidence of age-related disease. Fasting or dietary restriction (DR) can help prevent these via anti-ageing effects; however, these effects in neurons are less well characterized. Here, a series of animal and human studies of the effects of DR on the structural and functional integrity of neurons and the underlying mechanisms are analyzed. DR improves the integrity of animal neurons via a wide range of possible mechanisms including changes in metabolism, oxidative damage, stress responses, growth factors, and gene expression. These mechanisms are extensively interlinked and point to an optimum range of calorie intake, above calorie deprivation and below burdensome calorie excess. Human studies also suggest that DR improves neuron integrity; however, due to ethical and methodological limitations, the most conclusive data on DR hinge upon on going life-long monkey experiments. Rather than developing pharmacological mimetics of DR, our focus should be on educating the public about DR in order to minimize age-related disease. PMID- 26264850 TI - Simulation-based estimation of mean and standard deviation for meta-analysis via Approximate Bayesian Computation (ABC). AB - BACKGROUND: When conducting a meta-analysis of a continuous outcome, estimated means and standard deviations from the selected studies are required in order to obtain an overall estimate of the mean effect and its confidence interval. If these quantities are not directly reported in the publications, they must be estimated from other reported summary statistics, such as the median, the minimum, the maximum, and quartiles. METHODS: We propose a simulation-based estimation approach using the Approximate Bayesian Computation (ABC) technique for estimating mean and standard deviation based on various sets of summary statistics found in published studies. We conduct a simulation study to compare the proposed ABC method with the existing methods of Hozo et al. (2005), Bland (2015), and Wan et al. (2014). RESULTS: In the estimation of the standard deviation, our ABC method performs better than the other methods when data are generated from skewed or heavy-tailed distributions. The corresponding average relative error (ARE) approaches zero as sample size increases. In data generated from the normal distribution, our ABC performs well. However, the Wan et al. method is best for estimating standard deviation under normal distribution. In the estimation of the mean, our ABC method is best regardless of assumed distribution. CONCLUSION: ABC is a flexible method for estimating the study specific mean and standard deviation for meta-analysis, especially with underlying skewed or heavy-tailed distributions. The ABC method can be applied using other reported summary statistics such as the posterior mean and 95 % credible interval when Bayesian analysis has been employed. PMID- 26264851 TI - Barriers facing medical education are methodological, not financial. PMID- 26264852 TI - Process of care in outpatient Integrative healthcare facilities: a systematic review of clinical trials. AB - BACKGROUND: Patients currently integrate complementary medicine (CM) and allopathic, choosing a combination of therapies rather than a single therapy in isolation. Understanding integrative healthcare (IHC) extends beyond evaluation of specific therapies to encompass evaluations of multidisciplinary complex interventions. IHC is defined as a therapeutic strategy integrating conventional and complementary medical practices and practitioners in a shared care setting to administer an individualized treatment plan. We sought to review the outcomes of recent clinical trials, explore the design of the interventions and to discuss the methodological approaches and issues that arise when investigating a complex mix of interventions in order to guide future research. METHOD: Five databases were searched from inception to 30 March 2013. We included randomized and quasi experimental clinical trials of IHC. Data elements covering process of care (initial assessment, treatment planning and review, means for integration) were extracted. RESULTS: Six thousand two hundred fifty six papers were screened, 5772 were excluded and 484 full text articles retrieved. Five studies met the inclusion criteria. There are few experimental studies of IHC. Of the five studies conducted, four were in people with lower back pain. The positive findings of these studies indicate that it is feasible to conduct a rigorous clinical trial of an integrative intervention involving allopathic and CM treatment. Further, such interventions may improve patient outcomes. CONCLUSIONS: The trials in our review provide a small yet critical base from which to refine and develop larger studies. Future studies need to be adequately powered to address efficacy, safety and include data on cost effectiveness. PMID- 26264853 TI - Predictors of Recurrent AKI. AB - Recurrent AKI is common among patients after hospitalized AKI and is associated with progressive CKD. In this study, we identified clinical risk factors for recurrent AKI present during index AKI hospitalizations that occurred between 2003 and 2010 using a regional Veterans Administration database in the United States. AKI was defined as a 0.3 mg/dl or 50% increase from a baseline creatinine measure. The primary outcome was hospitalization with recurrent AKI within 12 months of discharge from the index hospitalization. Time to recurrent AKI was examined using Cox regression analysis, and sensitivity analyses were performed using a competing risk approach. Among 11,683 qualifying AKI hospitalizations, 2954 patients (25%) were hospitalized with recurrent AKI within 12 months of discharge. Median time to recurrent AKI within 12 months was 64 (interquartile range 19-167) days. In addition to known demographic and comorbid risk factors for AKI, patients with longer AKI duration and those whose discharge diagnosis at index AKI hospitalization included congestive heart failure (primary diagnosis), decompensated advanced liver disease, cancer with or without chemotherapy, acute coronary syndrome, or volume depletion, were at highest risk for being hospitalized with recurrent AKI. Risk factors identified were similar when a competing risk model for death was applied. In conclusion, several inpatient conditions associated with AKI may increase the risk for recurrent AKI. These findings should facilitate risk stratification, guide appropriate patient referral after AKI, and help generate potential risk reduction strategies. Efforts to identify modifiable factors to prevent recurrent AKI in these patients are warranted. PMID- 26264854 TI - Loss of Epithelial Membrane Protein 2 Aggravates Podocyte Injury via Upregulation of Caveolin-1. AB - Nephrotic syndrome is a CKD defined by proteinuria with subsequent hypoalbuminemia, hyperlipidemia, and edema caused by impaired renal glomerular filtration barrier function. We previously identified mutations in epithelial membrane protein 2 (EMP2) as a monogenic cause of this disease. Here, we generated an emp2-knockout zebrafish model using transcription activator-like effector nuclease-based genome editing. We found that loss of emp2 in zebrafish upregulated caveolin-1 (cav1), a major component of caveolae, in embryos and adult mesonephric glomeruli and exacerbated podocyte injury. This phenotype was partially rescued by glucocorticoids. Furthermore, overexpression of cav1 in zebrafish podocytes was sufficient to induce the same phenotype observed in emp2 homozygous mutants, which was also treatable with glucocorticoids. Similarly, knockdown of EMP2 in cultured human podocytes resulted in increased CAV1 expression and decreased podocyte survival in the presence of puromycin aminonucleoside, whereas glucocorticoid treatment ameliorated this phenotype. Taken together, we have established excessive CAV1 as a mediator of the predisposition to podocyte injury because of loss of EMP2, suggesting CAV1 could be a novel therapeutic target in nephrotic syndrome and podocyte injury. PMID- 26264856 TI - Bimodal Exciplex Formation in Bimolecular Photoinduced Electron Transfer Revealed by Ultrafast Time-Resolved Infrared Absorption. AB - The dynamics of a moderately exergonic photoinduced charge separation has been investigated by ultrafast time-resolved infrared absorption with the dimethylanthracene/phthalonitrile donor/acceptor pair in solvents covering a broad range of polarity. A distinct spectral signature of an exciplex could be identified in the -C=N stretching region. On the basis of quantum chemistry calculations, the 4-5 times larger width of this band compared to those of the ions and of the locally excited donor bands is explained by a dynamic distribution of exciplex geometry with different mutual orientations and distances of the constituents and, thus, with varying charge-transfer character. Although spectrally similar, two types of exciplexes could be distinguished by their dynamics: short-lived, "tight", exciplexes generated upon static quenching and longer-lived, "loose", exciplexes formed upon dynamic quenching in parallel with ion pairs. Tight exciplexes were observed in all solvents, except in the least polar diethyl ether where quenching is slower than diffusion. The product distribution of the dynamic quenching depends strongly on the solvent polarity: whereas no significant loose exciplex population could be detected in acetonitrile, both exciplex and ion pair are generated in less polar solvents, with the relative population of exciplex increasing with decreasing solvent polarity. These results are compared with those reported previously with donor/acceptor pairs in different driving force regimes to obtain a comprehensive picture of the role of the exciplexes in bimolecular photoinduced charge separation. PMID- 26264855 TI - Comparison of Glomerular and Podocyte mRNA Profiles in Streptozotocin-Induced Diabetes. AB - Evaluating the mRNA profile of podocytes in the diabetic kidney may indicate genes involved in the pathogenesis of diabetic nephropathy. To determine if the podocyte-specific gene information contained in mRNA profiles of the whole glomerulus of the diabetic kidney accurately reflects gene expression in the isolated podocytes, we crossed Nos3(-/-) IRG mice with podocin-rtTA and TetON-Cre mice for enhanced green fluorescent protein labeling of podocytes before diabetic injury. Diabetes was induced by streptozotocin, and mRNA profiles of isolated glomeruli and sorted podocytes from diabetic and control mice were examined 10 weeks later. Expression of podocyte-specific markers in glomeruli was downregulated in diabetic mice compared with controls. However, expression of these markers was not altered in sorted podocytes from diabetic mice. When mRNA levels of glomeruli were corrected for podocyte number per glomerulus, the differences in podocyte marker expression disappeared. Analysis of the differentially expressed genes in diabetic mice also revealed distinct upregulated pathways in the glomeruli (mitochondrial function, oxidative stress) and in podocytes (actin organization). In conclusion, our data suggest reduced expression of podocyte markers in glomeruli is a secondary effect of reduced podocyte number, thus podocyte-specific gene expression detected in the whole glomerulus may not represent that in podocytes in the diabetic kidney. PMID- 26264857 TI - Design of substrate-based BCR-ABL kinase inhibitors using the cyclotide scaffold. AB - The constitutively active tyrosine kinase BCR-ABL is the underlying cause of chronic myeloid leukemia (CML). Current CML treatments rely on the long-term use of tyrosine kinase inhibitors (TKIs), which target the ATP binding site of BCR ABL. Over the course of treatment, 20-30% of CML patients develop TKI resistance, which is commonly attributed to point mutations in the drug-binding region. We design a new class of peptide inhibitors that target the substrate-binding site of BCR-ABL by grafting sequences derived from abltide, the optimal substrate of Abl kinase, onto a cell-penetrating cyclotide MCoTI-II. Three grafted cyclotides show significant Abl kinase inhibition in vitro in the low micromolar range using a novel kinase inhibition assay. Our work also demonstrates that a reengineered MCoTI-II with abltide sequences grafted in both loop 1 and 6 inhibits the activity of [T315I]Abl in vitro, a mutant Abl kinase harboring the "gatekeeper" mutation which is notorious for being multidrug resistant. Results from serum stability and cell internalization studies confirm that the MCoTI-II scaffold provides enzymatic stability and cell-penetrating properties to the lead molecules. Taken together, our study highlights that reengineered cyclotides incorporating abltide-derived sequences are promising substrate-competitive inhibitors for Abl kinase and the T315I mutant. PMID- 26264858 TI - Reserve-building activities in multiple sclerosis patients and healthy controls: a descriptive study. AB - BACKGROUND: Cognitive reserve has been implicated as a possible protective factor in multiple sclerosis (MS) but to date no study has compared reserve-building activities across disease course or to healthy controls. This study aims to describe differences in reserve-building activities across the MS disease course and healthy controls. METHODS: Secondary analysis of a cross-sectional cohort study that included 276 healthy controls, and subjects with clinically isolated syndrome (CIS; n = 67), relapsing-remitting MS (RRMS; n = 358) and secondary progressive MS (PMS; n = 109). Past reserve-building activities were operationalized as occupational attainment and education. Current activities comprised 6 strenuous and 6 non-strenuous activities, including 5 reserve building activities and television-watching. Multivariate Analysis of Variance models examined group differences in past and current activities, after adjusting for covariates. RESULTS: There were group differences in past and current reserve building activities. SPMS patients had lower past reserve-building activities than healthy controls. All forms of MS engaged in fewer strenuous current reserve building pursuits than healthy controls. RRMS read less than healthy controls. SPMS engaged in fewer job-related non-strenuous activities. All MS groups watched more television than healthy controls. CONCLUSIONS: MS patients show significantly fewer past and present reserve-building activities. Although it is difficult to establish causality without future prospective studies, lifestyle modifying interventions should prioritize expanding MS patients' repertoire of strenuous and non-strenuous activities. PMID- 26264859 TI - Impaired cognition and cerebral glucose regulation are associated with astrocyte activation in the parenchyma of metabolically stressed APPswe/PS1dE9 mice. AB - Although metabolic syndrome was suggested to be a risk factor for Alzheimer's disease (AD), the role of metabolic stress in the initiation of AD pathology remains unclear. In this study, metabolic stress was induced by a high-fat diet and low-dose injection of streptozotocin (HFSTZ) before the appearance of senile plaques in APP/PS1 transgenic mice. We found that, HFSTZ treatment exacerbated amyloid beta burden and astrocyte activation in the vicinity of plaques. Moreover, we observed an upregulation of astrocytic S100B expression in the brain parenchyma of HFSTZ-treated APP/PS1 mice concurrent with increased interleukin-6 expression in cerebral microvascular cells. To determine the impact of HFSTZ treatment on brain function, we performed [(18)F]fludeoxyglucose-positron emission tomography and analyzed nesting behavior. HFSTZ treatment impaired nest construction and cerebral glucose metabolism in several brain regions of APP/PS1 mice during the early stage of AD. These results suggest that HFSTZ-induced peripheral metabolic stress may contribute to vascular inflammation and astrocyte reactivity in the parenchyma and may impair activity of daily living skill and cerebral glucose metabolism in APP/PS1 mice. PMID- 26264860 TI - Size-segregated emissions and metal content of vehicle-emitted particles as a function of mileage: Implications to population exposure. AB - The study aims at investigating the characteristics (size distribution, active surface and metal content) of particles emitted by cars as a function of mileage using a novel methodology for characterizing particulate emissions captured by Exhaust Gas Suspension (EGS). EGS was obtained by passing the exhaust gases through a container of deionized water. EGS analysis was performed using laser granulometry, electron scanning microscopy, and high resolution mass spectrometry. Implications of the differences in key features of the emitted particles on population exposure were investigated using numerical simulation for estimating size-segregated PM deposition across human respiratory tract (HRT). It was found that vehicle mileage, age and the respective emissions class have almost no effect on the size distribution of the exhaust gas particulate released into the environment; about half of the examined vehicles with low mileage were found to release particles of aerodynamic diameter above 10 MUm. The exhaust gas particulate detected in the EGS of all cars can be classified into three major size classes: (1) 0.1-5 um - soot and ash particles, metals (Au, Pt, Pd, Ir); (2) 10-30 um - metal (Cr, Fe, Cu, Zr, Ni) and ash particles; (3) 400-1,000 um - metal (Fe, Cr, Pb) and ash particles. Newer vehicles with low mileage are substantial sources of soot and metal particles with median diameter of 200 nm with a higher surface area (up to 89,871.16 cm(2)/cm(3)). These tend to deposit in the lower part of the human respiratory tract. PMID- 26264861 TI - Computational full electron structure study of biological activity in Cyclophilin A. AB - Cyclosporine (CsA) is widely used in organ transplant patients to help prevent the patient's body from rejecting the organ. CsA has been shown to be a safe and highly effective immunosuppressive drug that binds with the protein Cyclophilin A (CypA) at active sites. However, the exact mechanism of this binding at the molecular level remains unknown. In this project, we elucidate the binding of CsA to CypA at the molecular level by computing their electron structures and revealing their interactions. We employ a novel technique called electron Computer-Aided Drug Design (eCADD) on the protein's full electron structure along with its hydrophobic pocket and the perturbation theory of the interaction between two wave functions. We have identified the wave function of CypA, the biological active residues and active atoms of CypA and CsA, the interaction site between CypA and CsA, and the hydrogen bonds in the ligand CsA binding site. All these calculated active residues, active atoms, and hydrogen bonds are in good agreement with recorded laboratory experiments and provide guidelines for designing new ligands of CypA. We believe that our eCADD framework can provide researchers with a cost-efficient new method of drug design based on the full electron structure of proteins. PMID- 26264862 TI - Surface immobilization of a protease through an inhibitor-derived affinity ligand: a bioactive surface with defensive properties against an inhibitor. AB - The concept of enzyme immobilization via an inhibitor-derived peptide was developed. This method of immobilization was shown to be advantageous over physical adsorption and covalent bonding in retaining the enzymatic activity. Moreover, the surface-immobilized enzyme exhibited resistance against its inhibitor due to the occupation of an inhibitor binding site on the enzyme. PMID- 26264863 TI - Ethanol photocatalysis on rutile TiO2(110): the role of defects and water. AB - In this work we present a stoichiometric reaction mechanism for the photocatalytic ethanol oxidation on TiO2(110). The reaction products are analyzed either under reaction conditions or after irradiation at lower temperatures. Water is identified as a quantitative by-product, which resides in a defect site. These water molecules cause a blocking of the defect sites which results in poisoning of the catalyst. By different preparation techniques of the TiO2(110) surface, the role of surface defects is further elucidated and the role of molecular oxygen is investigated. Based on the investigation, a complete photochemical reaction mechanism is given, which provides insights into general photon driven oxidation mechanisms on TiO2. PMID- 26264864 TI - Ionization-induced annealing of pre-existing defects in silicon carbide. AB - A long-standing objective in materials research is to effectively heal fabrication defects or to remove pre-existing or environmentally induced damage in materials. Silicon carbide (SiC) is a fascinating wide-band gap semiconductor for high-temperature, high-power and high-frequency applications. Its high corrosion and radiation resistance makes it a key refractory/structural material with great potential for extremely harsh radiation environments. Here we show that the energy transferred to the electron system of SiC by energetic ions via inelastic ionization can effectively anneal pre-existing defects and restore the structural order. The threshold determined for this recovery process reveals that it can be activated by 750 and 850 keV Si and C self-ions, respectively. The results conveyed here can contribute to SiC-based device fabrication by providing a room-temperature approach to repair atomic lattice structures, and to SiC performance prediction as either a functional material for device applications or a structural material for high-radiation environments. PMID- 26264866 TI - Optimal criteria and sampling interval to detect a VO2 plateau at VO2max in patients with metabolic syndrome. AB - This study sought to determine the optimal criteria and sampling interval to detect a VO2 plateau at VO2max in patients with metabolic syndrome. Twenty-three participants with criteria-defined metabolic syndrome underwent a maximal graded exercise test. Four different sampling intervals and three different VO2 plateau criteria were analysed to determine the effect of each parameter on the incidence of VO2 plateau at VO2max. Seventeen tests were classified as maximal based on attainment of at least two out of three criteria. There was a significant (p < 0.05) effect of 15-breath (b) sampling interval on the incidence of VO2 plateau at VO2max across the <= 50 and <= 80 mL ? min(-1) conditions. Strength of association was established by the Cramer's V statistic (phic); (<= 50 mL ? min( 1) [phic = 0.592, p < 0.05], <= 80 mL ? min(-1) [phic = 0.383, p < 0.05], <= 150 mL ? min(-1) [phic = 0.246, p > 0.05]). When conducting maximal stress tests on patients with metabolic syndrome, a 15-b sampling interval and <= 50 mL ? min(-1) criteria should be implemented to increase the likelihood of detecting VO2 plateau at VO2max. PMID- 26264867 TI - Evaluating acellular versus cellular perfusate composition during prolonged ex vivo lung perfusion after initial cold ischaemia for 24 hours. AB - Normothermic ex vivo lung perfusion (EVLP) has developed as a powerful technique to evaluate particularly marginal donor lungs prior to transplantation. In this study, acellular and cellular perfusate compositions were compared in an identical experimental setting as no consensus has been reached on a preferred technique yet. Porcine lungs underwent EVLP for 12 h on the basis of an acellular or a cellular perfusate composition after 24 h of cold ischaemia as defined organ stress. During perfusion, haemodynamic and respiratory parameters were monitored. After EVLP, the lung condition was assessed by light and transmission electron microscopy. Aerodynamic parameters did not show significant differences between groups and remained within the in vivo range during EVLP. Mean oxygenation indices were 491 +/- 39 in the acellular group and 513 +/- 53 in the cellular group. Groups only differed significantly in terms of higher pulmonary artery pressure and vascular resistance in the cellular group. Lung histology and ultrastructure were largely well preserved after prolonged EVLP and showed only minor structural alterations which were similarly present in both groups. Prolonged acellular and cellular EVLP for 12 h are both feasible with lungs prechallenged by ischaemic organ stress. Physiological and ultrastructural analysis showed no superiority of either acellular or cellular perfusate composition. PMID- 26264868 TI - Basal cell carcinomas showing histological features generally associated with cutaneous adnexal neoplasms. AB - Basal cell carcinoma (BCC) is the commonest malignant neoplasm in humans. Although a histopathological diagnosis of BCC is straightforward in the vast majority of cases, unusual histological variants can present a diagnostic challenge. A small proportion of BCCs show features which are generally associated with cutaneous adnexal neoplasms. Such changes may involve either the epithelium or the stroma and can mislead the pathologist particularly in small biopsies. Despite the growing evidence which speculate that BCC is a primitive follicular tumor, it is unusual to encounter tumors which actually show definitive signs of adnexal differentiation. This review aims to address this somewhat overlooked aspect of a very common tumor and offers practical guidance to distinguish them from adnexal neoplasms which they might mimic. PMID- 26264870 TI - A facile approach to the synthesis of structurally diverse 6,8a-dihydropyrido[2,3 d]pyrimidine derivatives via a three-component domino reaction. AB - A concise and efficient approach to the synthesis of structurally diverse 6,8a dihydropyrido[2,3-d]pyrimidine derivatives has been accomplished by a three component reaction involving sulfonyl acetonitrile, an aromatic aldehyde, and 6 aminouracil. The method involves the domino Knoevenagel condensation/Michael addition/cyclization cascade in the presence of triethylamine in refluxing ethanol. PMID- 26264871 TI - MR derived volumetric flow rate waveforms of internal carotid artery in patients treated for unruptured intracranial aneurysms by flow diversion technique. AB - Little is known about the hemodynamic disturbances induced by the cerebral aneurysms in the parent artery and the effect of flow diverter stents (FDS) on these latter. A better understanding of the aneurysm-parent vessel complex relationship may aid our understanding of this disease and to optimize its treatment. The ability of volumetric flow rate (VFR) waveform to reflect the arterial compliance modifications is well known. By analyzing the VFR waveform and the pulsatility in the parent vessel, this study aimed to test the hypotheses that (1) intracranial aneurysms might disrupt the blood flow of the parent vessel and (2) the treatment by FDS might have measurable corrective effect on these changes. Ten patients followed for unruptured intracranial aneurysms treated by FDS and ten healthy volunteers as control group were included in this study. Two dimensional quantitative phase-contrast magnetic resonance imaging (MRI) was performed on each patient on the ICA artery upstream and downstream to the aneurysm, and on each volunteer at similar locations. The aneurysms altered significantly the parent vessel pulsatility and this effect was correlated to their volume. The aneurysms treatment by FDS allowed for the restoration of a normally modulated flow and pulsatility correction in the parent vessel. PMID- 26264872 TI - DULIP: A Dual Luminescence-Based Co-Immunoprecipitation Assay for Interactome Mapping in Mammalian Cells. AB - Mapping of protein-protein interactions (PPIs) is critical for understanding protein function and complex biological processes. Here, we present DULIP, a dual luminescence-based co-immunoprecipitation assay, for systematic PPI mapping in mammalian cells. DULIP is a second-generation luminescence-based PPI screening method for the systematic and quantitative analysis of co-immunoprecipitations using two different luciferase tags. Benchmarking studies with positive and negative PPI reference sets revealed that DULIP allows the detection of interactions with high sensitivity and specificity. Furthermore, the analysis of a PPI reference set with known binding affinities demonstrated that both low- and high-affinity interactions can be detected with DULIP assays. Finally, using the well-characterized interaction between Syntaxin-1 and Munc18, we found that DULIP is capable of detecting the effects of point mutations on interaction strength. Taken together, our studies demonstrate that DULIP is a sensitive and reliable method of great utility for systematic interactome research. It can be applied for interaction screening and validation of PPIs in mammalian cells. Moreover, DULIP permits the specific analysis of mutation-dependent binding patterns. PMID- 26264874 TI - Pathogenesis and Management of Buerger's Disease. AB - Buerger's disease or thromboangiitis obliterans causes pain, ulceration, or gangrene in the lower or upper extremity. It is associated with chronic cigarette smoking and is believed to be an immune mediated vasculitis. The pathogenesis is still unknown but recent postulate of its association with odontal bacteria has generated much renewed interest. Despite its recognition more than a century ago, little progress has been made in its treatment. Until the pathogenesis is elucidated, abstinence from cigarette is the only effective therapy. PMID- 26264873 TI - The Telomere Binding Protein Cdc13 and the Single-Stranded DNA Binding Protein RPA Protect Telomeric DNA from Resection by Exonucleases. AB - The telomere is present at the ends of all eukaryotic chromosomes and usually consists of repetitive TG-rich DNA that terminates in a single-stranded 3' TG extension and a 5' CA-rich recessed strand. A biochemical assay that allows the in vitro observation of exonuclease-catalyzed degradation (resection) of telomeres has been developed. The approach uses an oligodeoxynucleotide that folds to a stem-loop with a TG-rich double-stranded region and a 3' single stranded extension, typical of telomeres. Cdc13, the major component of the telomere-specific CST complex, strongly protects the recessed strand from the 5' >3' exonuclease activity of the model exonuclease from bacteriophage lambda. The isolated DNA binding domain of Cdc13 is less effective at shielding telomeres. Protection is specific, not being observed in control DNA lacking the specific TG rich telomere sequence. RPA, the eukaryotic single-stranded DNA binding protein, also inhibits telomere resection. However, this protein is non-specific, equally hindering the degradation of non-telomere controls. PMID- 26264875 TI - Case Series of HIV Infection-Associated Arteriopathy: Diagnosis, Management, and Outcome Over a 5-Year period at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University. AB - Patients infected with human immunodeficiency virus (HIV) can present with 4 pathology types: drug-induced vasospasm (ergotism), arterial limb ischemia, critical limb ischemia, and aneurysm. Although these problems are common vascular problems, they result in increased morbidity and mortality in HIV-infected patients, especially aneurysm. Patients with these problems tend to be diagnosed with difficulty because of atypical symptoms and signs. Because of lack of data in treatment outcome literature, our report explores and provides information on HIV infection-related arteriopathy. There were 17 patients in our 5-year review. There was no death in patients except the aneurysm type. The survival of aneurysm patients was significantly lower than from other pathologies (P = .003). Our case series showed good short-term outcome, and patients were not at risk for less beneficial surgical procedures. PMID- 26264876 TI - Autophagy-Induced Apoptosis in Lung Cancer Cells by a Novel Digitoxin Analog. AB - We have synthesized a novel derivative of Digitoxin, termed "MonoD", which demonstrates cytotoxic effects in lung cancer cells with much higher potency as compared to Digitoxin. Our data show that within 1 h of MonoD treatment, H460 cells showed increased oxidative stress, increased formation of autophagic vacuoles, and increased expression of pro-autophagic markers Beclin-1 and LC3-II. Cells pretreated with MnTBAP, a superoxide scavenger not only lowered superoxide production, but also had lower levels of LC3-II and Beclin-1. Prolonged treatment with MonoD-induced apoptosis in lung cancer cells. We investigated MonoD dependent regulation of Akt and Bcl2, proteins that are known regulators of both autophagy and apoptosis. Molecular and pharmacologic inhibitors of Bcl2 and Akt, when combined with MonoD, led to higher expression of LC3-II and Beclin-1 as compared to MonoD alone, suggesting a repressive effect for these proteins in MonoD-dependent autophagy. Pretreatment of cells with an autophagy inhibitor repressed the apoptotic potential of MonoD, confirming that early autophagic flux is important to drive apoptosis. Therapeutic entities such as MonoD that target multiple pathways such as autophagy and apoptosis may prove advantageous over current therapies that have unimodal basis for action and may drive sustained tumor regression, which is highly desirable. J. Cell. Physiol. 231: 817-828, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26264877 TI - Developmental changes between childhood and adulthood in passive observational and interactive feedback-based categorization rule learning. AB - As children start attending school they are more likely to face situations where they have to autonomously learn about novel object categories (e.g. by reading a picture book with descriptions of novel animals). Such autonomous observational category learning (OCL) gradually complements interactive feedback-based category learning (FBCL), where a child hypothesizes about the nature of a novel object, acts based on his prediction, and then receives feedback indicating the correctness of his prediction. Here we tested OCL and FBCL skills of elementary school children and adults. In both conditions, participants performed complex rule-based categorization tasks that required associating novel objects with novel category-labels. We expected children to perform better in FBCL tasks than in OCL tasks, whereas adults to be skilled in both tasks. As hypothesized, in early-phase learning children performed better in FBCL tasks than in OCL tasks. Unexpectedly, adults performed somewhat better in OCL tasks. Early-phase FBCL performance in the two age groups was matched, but the OCL performance of adults was higher than that of children. In late-phase learning there was only an age group main effect (adults > children). Moreover, performance in post-learning categorization tasks, that did not require label recollection, indicated that in FBCL tasks children were likely to directly learn the associations between an object and a category label, whereas in the OCL tasks they were likely to first learn which feature-dimensions were relevant. These findings shed light on developmental changes in cognitive control and learning mechanisms. Implications for educational settings are discussed. PMID- 26264878 TI - Surgical challenges in a new theater of modern warfare: The French role 2 in Gao, Mali. AB - INTRODUCTION: On January 11th 2013, France launched Operation Serval in Mali following Resolution 2085 of the Security Council of the United Nations. Between January and March 2013, more than 4000 French soldiers were deployed to support the Malian National Army and the African Armed Forces. METHODS: All of the patients who had surgery during Operation Serval were entered into a computerised database. Patients' demographic data (age, sex, status) and types of performed surgical procedures (specialties, injury mechanisms) were recorded. RESULTS: 268 patients were operated on in Gao's Role 2 with a total of 296 surgeries. Among those operated on, 40% were Malian civilians, 24% were French soldiers, and 36% were soldiers of the International Coalition Forces. The majority of the surgeries were orthopaedic, and visceral surgeries were common as well, representing 43% of the total surgeries. Specialised surgical procedures including neurosurgery, thoracic, and vascular surgery were also performed. Forty percent of the surgeries were scheduled. War-related traumatic surgeries represented 22% of the surgical procedures, with non-war related surgeries and non-trauma emergency surgeries making up the rest. CONCLUSION: this analysis confirms the specific characteristic of asymmetric warfare that it results in a relatively reduced number of war-related casualties. Forward surgical teams have to deal with a wide range of injuries requiring several surgical specialties. Surgeries dedicated to medical aid provided to the population also represented an important part of the surgical activity. Because of the diversity and the technicality of the surgical procedures in Role 2, surgeons had to be trained in war surgery covering all of the surgical specialties, while they maintained their specific skills. In France in 2007, the French Military Health Service Academy (Ecole du Val-de-Grace, Paris, France) offered an advanced course in surgery for deployment in combat zones, with a special focus on damage control surgeries and the management of mass casualties incidents. PMID- 26264879 TI - Prehospital ultrasound of the abdomen and thorax changes trauma patient management: A systematic review. AB - BACKGROUND: Ultrasound examination of trauma patients is increasingly performed in prehospital services. It is unclear if prehospital sonographic assessments change patient management: providing prehospital diagnosis and treatment, determining choice of destination hospital, or treatment at the receiving hospital. OBJECTIVE: This review aims to assess and grade the evidence that specifically examines whether prehospital ultrasound (PHUS) of the thorax and/or abdomen changes management of the trauma patient. METHODS: A systematic review was conducted of trauma patients who had an ultrasound of the thorax or abdomen performed in the prehospital setting. PubMed, MEDLINE, Web of Science (CINAHL, EMBASE, Cochrane Central Register of Controlled Trials) and the reference lists of included studies were searched. Methodological quality was checked and risk of bias analysis performed, a level of evidence grade was assigned, and descriptive data analysis performed. RESULTS: 992 unique citations were identified, which included eight studies that met inclusion criteria with a total of 925 patients. There are no reports of randomised controlled trials. Heterogeneity exists between the included studies which ranged from a case series to retrospective and prospective non-randomised observational studies. Three studies achieved a 2+ Scottish Intercollegiate Guidelines Networks grade for quality of evidence and the remainder demonstrated a high risk of bias. The three best studies each provided examples of prehospital ultrasound positively changing patient management. CONCLUSION: There is moderate evidence that supports prehospital physician use of ultrasound for trauma patients. For some patients, management was changed based on the results of the PHUS. The benefit of ultrasound use in non-physician services is unclear. PMID- 26264880 TI - An audit of penetrating neck injuries in a South African trauma service. AB - INTRODUCTION: This study reviews and validates the practice of selective non operative management (SNOM) of penetrating neck injury (PNI) in a South African trauma service and reviews the impact new imaging modalities have had on the management of this injury. METHODOLOGY: This study was performed within the Pietermaritzburg Metropolitan Trauma Service, in the city of Pietermaritzburg, Kwazulu-Natal, South Africa. A prospectively maintained trauma registry was retrospectively interrogated. All patients with PNI treated over a 46-month period were included within the study. RESULTS: A total of 510 patients were included in the study. There were 452 stab wounds (SW) and 58 gunshot wounds (GSW). A total of 202 (40%) patients sustained isolated PNI, the remaining 308 (60%) patients sustained trauma to at least one additional anatomical region. An airway injury was identified in 29 (6%) patients; a pharyngo-oesophageal injury in 41 (8%) patients and a vascular injury in 86 (17%) patients. Associated injuries included three penetrating cardiac injuries (PCI) and 146 patients with haemo-pneumothoraces. Of the total cohort, 387 patients (76%) underwent CT Angiography (CTA), of which 70 (18%) demonstrated a vascular injury. Formal catheter directed angiogram (CDA) was performed on 16 patients with positive CTA but confirmed injury in only half of these patients. Of 212 patients (42%) who underwent water-soluble contrast swallow (WS-swallow), an injury was demonstrated in 29 (14%) cases. A total of 401 (79%) patients were successfully managed conservatively for PNI and 109 (21%) surgically or by endovascular intervention. Only five (1.2%) patients failed a trial of SNOM and required surgery. The in hospital mortality rate was 2%. No deaths could be attributed to a failure of SNOM. CONCLUSION: SNOM of PNI is a safe and appropriate management strategy. The conservative management of isolated pharyngeal injuries is well supported by our findings but the role of conservative treatment of oesophageal injuries needs to be further defined. The SNOM of small non-destructive upper airway injuries seems to be a safe strategy, while destructive airway injuries require formal repair. Imaging merely for proximity, is associated with a low yield. CTA has a significant false positive rate and good clinical assessment remains the cornerstone of management. PMID- 26264881 TI - Subtrochanteric fracture: the effect of cerclage wire on fracture reduction and outcome. AB - INTRODUCTION: Subtrochanteric neck of femur fractures are a challenge to treat due to anatomical and biomechanical factors. Poor reduction, varus deformity, nonunion and return to theatre risks are high. A cerclage wire can augment an intramedullary nail to help fracture reduction and construct stability. Concerns exist regarding the use of cerclage wire on fracture zone vascularity. The aim of this study was to assess the benefits and adverse outcomes associated with the use of cerclage wiring. PATIENTS AND METHODS: A 7-year retrospective review of all subtrochanteric fractures at a Level 1 trauma centre was performed. Pathological fractures, those associated with bisphosphonate use and segmental fractures were excluded. A clinical and radiographic review was performed. Our primary outcome measure was a composite of the major complications of this surgery, defined as either return to theatre for fixation failure, nonunion or implant failure. Fracture displacement, angulation and quality of reduction were measured as secondary outcome measures. Specific complications of the use of cerclage wiring were also reported. RESULTS: One hundred and thirty four cases met the inclusion criteria for primary outcome. Reduction was achieved closed in 51.9% (n=70), open in 33.3% (n=45) and open with cerclage wire in 14.8% (n=20). Overall there were a total of 13 (9.7%) major complications. No cases with cerclage wire had a return to theatre. If cerclage wire was not used the major complication rate was 11.4%. Fracture displacement (11.0mm vs. 7.69mm) and distraction were related to return to theatre (p<0.05). Cerclage wire use improved fracture displacement (3.2mm vs. 8.8mm), angulation and quality of reduction (p<0.05). CONCLUSIONS: Anatomical reduction is the key to success of subtrochanteric fractures. Cerclage wire use results in better fracture reduction. Some subtrochanteric fractures can be successfully treated with indirect reduction alone. If fractures cannot be reduced closed, reduction should be achieved by open methods. If a fracture is opened, a cerclage wire should be used, if the fracture pattern allows. PMID- 26264882 TI - Moderate- and high-intensity exhaustive exercise in the heat induce a similar increase in monocyte Hsp72. AB - This study examined the relationship between exhaustive exercise in the heat at moderate and high intensities on the intracellular heat shock protein 72 (iHsp72) response. Twelve male subjects cycled to exhaustion at 60 and 75% of maximal oxygen uptake in hot conditions (40 degrees C, 50% RH). iHsp72 concentration was measured in monocytes before, at exhaustion and 24 h after exercise. Rectal temperature, heart rate and oxygen uptake were recorded during exercise. Volitional exhaustion occurred at 58.9 +/- 12.1 and 27.3 +/- 9.5 min (P < 0.001) and a rectal temperature of 39.8 +/- 0.4 and 39.2 +/- 0.6 degrees C (P = 0.002), respectively, for 60 and 75 %. The area under the curve above a rectal temperature of 38.5 degrees C was greater at 60 % (17.5 +/- 6.6 degrees C min) than 75 % (3.4 +/- 4.8 degrees C min; P < 0.001), whereas the rate of increase in rectal temperature was greater at 75 % (5.1 +/- 1.7 vs. 2.2 +/- 1.4 degrees C h(-1); P < 0.001). iHsp72 concentration increased similarly at exhaustion relative to pre-exercise (P = 0.044) and then increased further at 24 h (P < 0.001). Multiple regression analysis revealed no predictor variables associated with iHsp72 expression; however, a correlation was observed between exercise intensities for the increase in iHsp expression at exhaustion and 24 h (P < 0.05). These results suggest that iHsp72 expression increased in relation to the level of hyperthermia attained and sustained at 60 % and the higher metabolic rate and greater rate of increase in core temperature at 75 %, with the further increase in iHsp72 concentration 24 h after exercise reinforcing its role as a chaperone and cytoprotective agent. PMID- 26264883 TI - Test-retest Reliability and Measurement Error Are Excellent for the Dutch Version of the VascuQol Questionnaire in Patients with Intermittent Claudication. AB - OBJECTIVES: Although the Vascular Quality of Life Questionnaire (VascuQol) is a widely used instrument to assess quality of life in patients with peripheral arterial disease (PAD), data on its reliability are scarce and its measurement error is unknown. The aim of this study was to determine test-retest reliability and measurement error of the Dutch version of the VascuQol in patients with intermittent claudication (IC). METHODS: Patients with intermittent claudication due to PAD presenting between October 2013 and April 2014 completed the VascuQol twice, with a 1 week interval. Test-retest reliability was expressed as the intraclass correlation coefficient (ICC) with 95% confidence interval (CI), and measurement error as a standard error of measurement (SEM). RESULTS: Sixty-one patients completed two VascuQol questionnaires sufficiently. The ICC for the VascuQol sumscore was 0.91 (95% CI 0.86-0.95). The ICC for the different VascuQol domains ranged between 0.77 (95% CI 0.64-0.86) and 0.87 (95% CI 0.79-0.92). The SEM of the sumscore was 0.34 and ranged between 0.44 and 0.76 for the different VascuQol domains. CONCLUSIONS: The test-retest reliability of the Dutch version of the VascuQol is excellent, both for the sumscore and for its different domains. The VascuQol has a measurement error that is sufficiently small to allow detection of clinically relevant changes. PMID- 26264884 TI - More on the genetical theory of multilevel selection. AB - In my article The genetical theory of multilevel selection, I provided a synthesis of the theory of multilevel selection (MLS) and the theory of natural selection in class-structured populations. I framed this synthesis within Fisher's genetical paradigm, taking a strictly genetical approach to traits and fitness. I showed that this resolves a number of long-standing conceptual problems that have plagued the MLS literature, including the issues of 'aggregate' vs. 'emergent' group traits, 'collective fitness1 ' vs. 'collective fitness2 ' and 'MLS1' vs. 'MLS2 '. In his commentary, Goodnight suggests this theoretical and conceptual synthesis is flawed in several respects. Here, I show this is incorrect, by: reiterating the theoretical and conceptual goals of my synthesis; clarifying that my genetical approach to traits is necessary for a proper analysis of the action of MLS independently of non-Darwinian factors; emphasizing that the Price-Hamilton approach to MLS provides a consistent, useful and conceptually superior theoretical framework; and explaining the role of reproductive value in the study of natural selection in class-structured populations. I also show that Goodnight's contextual analysis treatment of MLS in a class-structured population is mathematically, biologically and conceptually inadequate. PMID- 26264886 TI - Comment on 'Transient memory impairment and transient global amnesia induced by photodynamic therapy'. PMID- 26264885 TI - Cross-sectional relationships between dietary fat intake and serum cholesterol fatty acids in a Swedish cohort of 60-year-old men and women. AB - BACKGROUND: The present study aimed to describe the relationship between self reported dietary intake and serum cholesterol fatty acids (FAs) in a Swedish population of 60-year-old men and women. METHODS: Cross-sectional data collected in 1997-1998 from 4232 individuals residing in Stockholm County were used. Five diet scores were created to reflect the intake of saturated fats in general, as well as fats from dairy, fish, processed meat and vegetable oils and margarines. Gas chromatography was used to assess 13 FAs in serum cholesterol esters. The association between each diet score and specific FAs was assessed by percentile differences (PD) with 95% confidence intervals (CI) at the 10th, 25th, 50th, 75th and 90th percentile of each FA across levels of diet scores using quantile regression. RESULTS: Fish intake was associated with high proportions of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). For each point increase in fish score, the 50th PD in EPA and DHA was 32.78% (95% CI = 29.22% to 36.35%) and 10.63% (95% CI = 9.52% to 11.74%), respectively. Vegetable fat intake was associated with a high proportion of linoleic acid and total polyunsaturated fatty acids (PUFA) and a low proportion of total saturated fatty acids (SFA). The intake of saturated fats in general and dairy fat was slightly associated with specific SFA, although the intake of fat from meat was not. CONCLUSIONS: In the present study population, using a rather simple dietary assessment method, the intake of fish and vegetable fats was clearly associated with serum PUFA, whereas foods rich in saturated fats in general showed a weak relationship with serum SFA. Our results may contribute to increased knowledge about underlying biology in diet-cardiovascular disease associations. PMID- 26264887 TI - Profiling the metabolome changes caused by cranberry procyanidins in plasma of female rats using (1) H NMR and UHPLC-Q-Orbitrap-HRMS global metabolomics approaches. AB - SCOPE: The objective was to investigate the metabolome changes in female rats gavaged with partially purified cranberry procyanidins (PPCP) using (1) H NMR and UHPLC-Q-Orbitrap-HRMS metabolomics approaches, and to identify the contributing metabolites. METHODS AND RESULTS: Twenty-four female Sprague-Dawley rats were randomly separated into two groups and administered PPCP or partially purified apple procyanidins (PPAP) for three times using a 250 mg extracts/kg body weight dose. Plasma was collected 6 h after the last gavage and analyzed using (1) H NMR and UHPLC-Q-Orbitrap-HRMS. No metabolome difference was observed using (1) H NMR metabolomics approach. However, LC-HRMS metabolomics data show that metabolome in the plasma of female rats administered PPCP differed from those gavaged with PPAP. Eleven metabolites were tentatively identified from a total of 36 discriminant metabolic features based on accurate masses and/or product ion spectra. PPCP caused a greater increase of exogenous metabolites including p hydroxybenzoic acid, phenol, phenol-sulphate, catechol sulphate, 3, 4 dihydroxyphenylvaleric acid, and 4'-O-methyl-(-)-epicatechin-3'-O-beta glucuronide in rat plasma. Furthermore, the plasma level of O-methyl-(-) epicatechin-O-glucuronide, 4-hydroxy-5-(hydroxyphenyl)-valeric acid-O-sulphate, 5 (hydroxyphenyl)-Upsilon-valerolactone-O-sulphate, 4-hydroxydiphenylamine, and peonidin-3-O-hexose were higher in female rats administered with PPAP. CONCLUSION: The metabolome changes caused by cranberry procyanidins were revealed using an UHPLC-Q-Orbitrap-HRMS global metabolomics approach. Exogenous and microbial metabolites were the major identified discriminate biomarkers. PMID- 26264888 TI - Clinical praxis for assessment of dry weight in Sweden and Denmark: A mixed methods study. AB - Overhydration is an independent predictor of mortality in hemodialysis (HD) patients. More than 30% of HD patients are overhydrated, motivating the development of new methods for assessing hydration status. This study surveyed clinical praxis and local guidelines for dry weight (DW) assessment in Swedish and Danish HD units, and examined if differences in routines and utilization of bioimpedance spectroscopy (BIS) and other assistive technology affected frequency of DW adjustments and blood pressure (BP) levels. Cross-sectional information on praxis, guidelines and routines, plus treatment-related data from 99 stratified patients were collected. Qualitative data were analyzed with content analysis and interpreted in convergence with statistical analysis of quantitative data in a mixed-methods design. Local guidelines concerning DW existed in 54% of the units. A BIS device was present in 52%, but only half of those units used it regularly, and no correlations to frequency of DW adjustments or BP were found. HD nurses were authorized to adjust DW in 60% of the units; in these units, the frequency of DW adjustments was 1.6 times higher and systolic BP pre-HD 8 mmHg lower. There is a wide variation in routines for DW determination, and there are indications that authorization of HD nurses to adjust DW may improve DW assessment. BIS is sparsely used; its implementation may have been delayed by uncertainty over how to manage the device and interpret measurements. Hence, better methods and guidelines for assessing DW and using BIS need to be developed. PMID- 26264889 TI - Natural killer cells regulate T cell immune responses in primary biliary cirrhosis. AB - The hallmark of primary biliary cirrhosis (PBC) is the presence of autoreactive T and B-cell responses that target biliary epithelial cells (BECs). Biliary cell cytotoxicity is dependent upon initiation of innate immune responses followed by chronic adaptive, as well as bystander, mechanisms. Critical to these mechanisms are interactions between natural killer (NK) cells and BECs. We have taken advantage of the ability to isolate relatively pure viable preparations of liver derived NK cells, BECs, and endothelial cells, and studied interactions between NK cells and BECs and focused on the mechanisms that activate autoreactive T cells, their dependence on interferon (IFN)-gamma, and expression of BEC major histocompatibility complex (MHC) class I and II molecules. Here we show that at a high NK/BEC ratio, NK cells are cytotoxic for autologous BECs, but are not dependent on autoantigen, yet still activate autoreactive CD4(+) T cells in the presence of antigen presenting cells. In contrast, at a low NK/BEC ratio, BECs are not lysed, but IFN-gamma production is induced, which facilitates expression of MHC class I and II molecules on BEC and protects them from lysis upon subsequent exposure to autoreactive NK cells. Furthermore, IFN-gamma secreted from NK cells after exposure to autologous BECs is essential for this protective function and enables autoreactive CD4(+) T cells to become cytopathic. CONCLUSIONS: NK cell-mediated innate immune responses are likely critical at the initial stage of PBC, but also facilitate and maintain the chronic cytopathic effect of autoantigen-specific T cells, essential for progression of disease. PMID- 26264890 TI - Proposed criteria for identifying GE crop plants that pose a low or negligible risk to the environment under conditions of low-level presence in seed. AB - The low-level presence (LLP) of genetically engineered (GE) seeds that have been approved in the country of origin but not the country of import presents challenges for regulators in both seed importing and exporting countries, as well as for the international seed trade and the farmers who rely on it. In addition to legal, financial and regulatory challenges, such LLP situations in seed may also require an environmental risk assessment by the country of import. Such assessments have typically been informed by the national framework established to support decisions related to wide scale cultivation, and frequently do not take into account the low environmental exposure and prior regulatory history of the GE plant. In addition, such assessment processes may not be well suited to the decision-making timeframe that is necessary when dealing with an LLP situation in imported seed. In order to facilitate regulatory decision making, this paper proposes a set of scientific criteria for identifying GE crop plants that are expected to pose a low or negligible risk to the environment under LLP conditions in seed. Regulatory decision makers in some importing countries may decide to use these criteria to assist in risk analysis associated with LLP situations they are experiencing or could experience in the future, and might choose to proactively apply the criteria to identify existing GE plants with regulatory approvals in other countries that would be expected to pose low risk under conditions of LLP in seed. PMID- 26264892 TI - Morphometric Study of Diabetes Related Alterations in Human Parotid Gland and Comparison with Submandibular Gland. AB - Type 2 diabetes mellitus represents one of the principal diseases that afflict the world population and is often associated with malfunction of salivary glands and consequent oral diseases. We recently described significant ultrastructural alterations in the human submandibular gland in diabetic patients without evident oral pathologies. Herein, an analogs morphometrical investigation was focused on the parotid gland in order to evaluate if one of the two glands is more affected by diabetes. Parotid fragments from diabetic and nondiabetic patients were fixed, dehydrated, and processed for light and electron microscopy. Serous cells were randomly photographed and the density and size of several structures involved in the secretory process were examined by morphometry. Scanning electron microscopy images revealed significant changes in the number of apically docked granules and vesicles, suggesting that the last steps in exocytosis are somehow altered in diabetic cells. Other variables analyzed by light and transmission electron microscopy such as the size of acini and secretory granules did not show significant changes, but comparison with previous data obtained with submandibular gland cells demonstrated that the two glands are affected differently. PMID- 26264893 TI - Communitywide cryptosporidiosis outbreak associated with a surface water-supplied municipal water system--Baker City, Oregon, 2013. AB - Cryptosporidium, a parasite known to cause large drinking and recreational water outbreaks, is tolerant of chlorine concentrations used for drinking water treatment. Human laboratory-based surveillance for enteric pathogens detected a cryptosporidiosis outbreak in Baker City, Oregon during July 2013 associated with municipal drinking water. Objectives of the investigation were to confirm the outbreak source and assess outbreak extent. The watershed was inspected and city water was tested for contamination. To determine the community attack rate, a standardized questionnaire was administered to randomly sampled households. Weighted attack rates and confidence intervals (CIs) were calculated. Water samples tested positive for Cryptosporidium species; a Cryptosporidium parvum subtype common in cattle was detected in human stool specimens. Cattle were observed grazing along watershed borders; cattle faeces were observed within watershed barriers. The city water treatment facility chlorinated, but did not filter, water. The community attack rate was 28.3% (95% CI 22.1-33.6), sickening an estimated 2780 persons. Watershed contamination by cattle probably caused this outbreak; water treatments effective against Cryptosporidium were not in place. This outbreak highlights vulnerability of drinking water systems to pathogen contamination and underscores the need for communities to invest in system improvements to maintain multiple barriers to drinking water contamination. PMID- 26264895 TI - Readmissions Following Gastric Bypass Surgery. AB - BACKGROUND: Interest is growing in preventing readmissions as payers start to link reimbursement to readmission rates. The purpose of this study was to assess factors contributing to 30-day readmission for patients undergoing gastric bypass (GB) and determine whether these readmissions may be preventable. METHODS: Data were from the Pennsylvania Health Care Cost Containment Council (PHC4) and included all patients undergoing elective GB for obesity in 2011 (n = 4427). The outcomes measured were length of stay (LOS) and 30-day readmission. Univariate comparisons between characteristics of readmitted (n = 298) and non-readmitted (n = 4133) patients were performed. Readmission was modeled using multivariate logistic regression; LOS was modeled using linear regression. RESULTS: Of the 298 (6.6%) patients who were readmitted, the most common causes for readmission were bleeding (11.84%), infection (8.88%), and abdominal pain (7.89%). In multivariate analyses, black race, open GB, and history of myocardial infarction or rheumatoid arthritis were associated with increased odds of readmission. Longer LOS was also predictive of readmission (OR 1.10, p = <0.0001). Patients who were >50 years old and those with history of congestive heart failure, peripheral vascular, and kidney diseases were more likely to have longer LOS. Black race, open surgery, and discharge to an extended care facility were also predictive of prolonged LOS. CONCLUSIONS: The most common causes of readmission following elective GB were bleeding, infection, and abdominal pain. Since several patient-specific factors were associated with higher odds of readmission and longer LOS, there are opportunities to design interventions to prevent readmissions and decrease LOS in this patient population. PMID- 26264894 TI - The intersection of cancer, cancer stem cells, and the immune system: therapeutic opportunities. AB - During brain neoplasia, malignant cells subjugate the immune system to provide an environment that favors tumor growth. These mechanisms capitalize on tumor promoting functions of various immune cell types and typically result in suppression of tumor immune rejection. Immunotherapy efforts are underway to disrupt these mechanisms and turn the immune system against developing tumors. While many of these therapies are already in early-stage clinical trials, understanding how these therapies impact various tumor cell populations, including self-renewing cancer stem cells, may help to predict their efficacy and clarify their mechanisms of action. Moreover, interrogating the biology of glioma cell, cancer stem cell, and immune cell interactions may provide additional therapeutic targets to leverage against disease progression. In this review, we begin by highlighting a series of investigations into immune cell-mediated tumor promotion that do not parse the tumor into stem and non-stem components. We then take a closer look at the immune-suppressive mechanisms derived specifically from cancer stem cell interactions with the immune system and end with an update on immunotherapy and cancer stem cell-directed clinical trials in glioblastoma. PMID- 26264896 TI - Functional changes in Hofbauer cell glycobiology during human pregnancy. AB - INTRODUCTION: This study examines the glucose metabolism and glycosylation of villous macrophages (Hofbauer cells) over the course of pregnancy. MATERIALS AND METHODS: Sections of placentae from 6 weeks to term were stained with antibodies to alpha-amylase, glycogen synthase, glycogen phosphorylase and glucose transporters 1 and 3 (GLUT-1 and GLUT-3) while a panel of 24 lectins was applied to resin sections from 4 weeks onwards. Hofbauer cells were identified by the binding of anti-CD 163 antibody. RESULTS: Little stored glycogen could be demonstrated by Bandeiraea simplicifolia-II agglutinin binding and, by immunocytochemistry, low levels of glycogen synthase were located within the cells, though glycogen phosphorylase expression, an enzyme releasing glucose from glycogen chains, was intense. Glucose transporter-3 but not -1 was present in the cells as has been found in other types of macrophage. Lectin histochemistry showed that many classes of glycan were present in the cells, both N and O linked, though simple fucose residues could not be demonstrated. Glycan profiles were obtained for Hofbauer cell plasma membranes, cytosol, lysosomes and small granules. With some lectins, the intensity of binding diminished after the second trimester. Morphological changes also occurred over the course of pregnancy. DISCUSSION: Hofbauer cells have properties commensurate with their phagocytic activity with numerous lysosomal vacuoles and heavily glycosylated plasma membranes and granules, most evident in the first half of pregnancy. Their carbohydrate metabolism appears to rely on glucose mobilisation rather than storage as glycogen, reflecting their peripatetic mode of existence. PMID- 26264897 TI - [Neuropathic pain. How to open the blackbox]. AB - This article, without presuming to be comprehensive, gives a brief outline of the development of research on neuropathic pain in Germany. Current clinical research on this subject focusses on the validation of human models, patient phenotyping, mechanism-based classification and treatment as well as on molecular pathomechanisms. This clinical research is based to a large extent on the work of several internationally recognized basic researchers in the 1990s. In particular, findings from system physiology led to the analysis of clinical phenotypes and the underlying pathophysiology. In parallel, basic research achieved international top levels through the development of innovative methods. Close cooperation, building of consortia and European networking made major contributions to the success of this research. PMID- 26264898 TI - [Opioids for noncancer pain in the elderly]. AB - BACKGROUND: Opioids are increasingly used in the elderly. Side effects differ compared to other analgesics. PURPOSE: In this review article, special aspects about using opioids for noncancer pain in older people and in geriatric patients are identified. CURRENT SITUATION: So far randomized controlled trials for the indication of and comparison between various opioids have been performed in middle-aged patients and not exclusively in geriatric patients or elderly (> 75 years). Furthermore, the evidence for multimorbid elderly patients with respect to side effects is also very poor. RECOMMENDATIONS: The indication for opioid therapy should be narrow. The patient and their caregivers must be provided patient information regarding opioid therapy. The principle "start low, go slow" is highly recommended. To reduce the risk of falls, longer acting opioids should be used and short acting opioids should be avoided. Everyday relevant negative effects on cognition are possible in opioid use and have to be observed. As recommended in the recently published German guideline for long-term use of opioids in noncancer pain a critical check after 3 months and in case of dosing over 120 mg morphine equivalents is advisable, especially for older patients. Liver and kidney function and drug interactions have to be taken into consideration like in every age group. PMID- 26264899 TI - [Healthcare services research on pain in Germany. A survey]. AB - Within the last ten years healthcare services research has developed into an independent interdisciplinary field of research. A selective search of the literature was conducted in the database Google Scholar and the database on healthcare services research in Germany (http://versorgungsforschung deutschland.de) for healthcare services research projects on pain in Germany. Healthcare services research projects were conducted by pharmaceutical companies, patient self-help organizations, scientific societies, statutory health insurance companies and university departments on acute and chronic pain. Valid data on the epidemiology, grading and treatment of chronic pain are available. There was an overuse of opioids and invasive procedures in patients with chronic low back pain, fibromyalgia syndrome and somatoform pain disorders. Databases for patients with chronic pain are currently constructed by pain societies. The fragmentation of data from health insurance companies, old age pension insurances, clinical institutions and population surveys and inconsistencies in diagnosing or encoding chronic pain impede the carrying out of significant longitudinal studies. Based on the data available, the needs of care for patients with chronic pain and the necessary care services cannot be derived. Important topics of future healthcare services research on pain are longitudinal studies on the cost efficacy and risks of inpatient and outpatient pain therapy based on routine data of health insurance companies, old age pension insurances and pain registries, longitudinal studies on "patient careers" (i.e. sequences of healthcare) and the identification of potential starting points for control of healthcare. PMID- 26264900 TI - [Pain medicine from intercultural and gender-related perspectives]. AB - Cultural setting and sex and gender of the patient are important factors affecting the occurrence, severity, clinical course and prognosis of pain and pain-related diseases. Intercultural differences in the perception and verbal expression of symptoms and emotional function are fundamental and it is important to realize these differences in order to understand patients with a migration background. A trusting doctor-patient relationship is generally very sensitive and it is even more difficult to establish when differences in the cultural background impair mutual understanding. Regarding sex and gender there is evidence that females are more susceptible to developing chronic pain conditions, experience more severe pain and respond differently to pain therapy; however, results of recent studies indicate that females are not that different to males when comparing several modalities of experimental pain (although some differences exist). Similarly, sex and gender differences in postoperative pain seem to exist but the differences are relatively small when pain scores are compared. Other aspects, such as the response to analgesics and role of psychosocial factors should be addressed when sex and gender aspects are studied. Similarly, sex and gender differences in the prevalence of chronic pain exist but the results of some studies, e.g. those controlling for confounders, are not very clear. Research is needed to delineate the role of specific aspects affecting sex and gender differences and the underlying mechanisms (e.g. reduced inhibitory control, hormones, psychological aspects and social factors). Altogether, we need to open our minds to some intercultural and sex and gender aspects in the clinical setting. For sex and gender differences we may need a more biopsychosocial approach to understand the underlying differences and differentiate between sex and gender and sex and gender-associated aspects for acute and chronic pain. PMID- 26264901 TI - [Headache. Current status of research and treatment]. AB - The starting point for German headache research and clinical education was the engagement of D. Soyka in the 1970s, which enabled the foundation of the German Headache Society (DMKG) on 28 June 1979 and, some years later, the founding congress of the International Headache Society (IHS) in Munich 1982. As a result of these activities, in 1988 the first international classification of headache disorders was published. This classification was one of the major milestones in the development of basic as well as clinical headache research. In the following years, epidemiological studies all over the world showed a 1-year prevalence for headache of approximately 60%, making headaches one of the most frequent medical complaints. Basic research showed an involvement of serotonergic mechanisms in migraine pain and triptans were one of the first drugs designed to influence these mechanisms. Functional brain imaging studies in migraine patients further showed a cyclic modulation of the activity of brainstem areas independent of the current pain state. Various research groups were involved in the clarification of the role of calcitonin gene-related peptide (CGRP) in migraine and cluster headache. A specific development in the German headache scene is the establishment of integrated headache centers and reflects the primarily multimodal treatment approach in Germany which contrasts with the settings in other countries. These successful developments are increasingly being undermined by the fact that the low financial support of headache research, for example, by the German science council is causing a decreasing interest in headache research, with the consequence that the clinical education of students as well as young medical doctors shows increasing deficits. The consequence for the future will be a deficit in the clinical care of the population. PMID- 26264902 TI - The effect of personal medical history and family history of cancer on the uptake of risk-reducing salpingo-oophorectomy. AB - Women with an increased lifetime risk of ovarian cancer are advised to undergo risk-reducing salpingo-oophorectomy (RRSO) to reduce risk of adnexal cancer. We investigated the uptake of RRSO and evaluated the influence of personal medical history of (breast) cancer, risk-reducing mastectomy (RRM) and family history of ovarian and/or breast cancer on the RRSO decision. This single center retrospective observational cohort study was performed in a tertiary multidisciplinary clinic for hereditary cancer of the University Medical Centre Utrecht, The Netherlands. Women >=35 years old with an estimated lifetime risk of ovarian cancer >=10%, who had completed childbearing, were eligible for RRSO. Uptake and timing of RRSO were analyzed. Influence of personal medical history and family history on RRSO decision making, were evaluated with logistic regression. The study population consisted of 218 women (45.0% BRCA1 mutation carrier, 28.0% BRCA2 mutation carrier, 27.0% with familial susceptibility) with 87.2% RRSO uptake. The median age at RRSO was 44.5 (range 28-73) years. Of the women undergoing RRSO, 78.3% needed <=3 consultations to reach this decision. Multivariable analysis showed a significant difference in RRSO uptake for women with a history of RRM [OR 3.66 95% CI (1.12-11.98)], but no significant difference in women with a history of breast cancer [OR 1.38 95% CI (0.50-3.79)], nor with a family history of ovarian and/or breast cancer [OR 1.10 95% CI (0.44 2.76)]. We conclude that RRSO counseling, without the alternative of screening, is effective. The uptake is increased in women with a history of RRM. PMID- 26264903 TI - Resilience to amphetamine in mouse models of netrin-1 haploinsufficiency: role of mesocortical dopamine. AB - RATIONALE: Signaling through the netrin-1 receptor, deleted in colorectal cancer (DCC), in dopamine neurons controls the extent of their innervation to the medial prefrontal cortex (mPFC) during adolescence. In mice, dcc haploinsufficiency results in increased mPFC dopamine innervation and concentrations in adulthood. In turn, dcc haploinsufficiency leads to resilience to the effects of stimulant drugs of abuse on dopamine release in the nucleus accumbens and behavior. OBJECTIVES: First, we set out to determine whether increased mPFC dopamine innervation causes blunted behavioral responses to amphetamine in adult dcc haploinsufficient mice. Second, we investigated whether unc5c, another netrin-1 receptor expressed by dopamine neurons, is involved in these effects. Third, we assessed whether haploinsufficiency of netrin-1 itself leads to blunted behavioral responding to amphetamine, whether this phenotype emerges before or after adolescence and whether increased mPFC dopamine input is the underlying mechanism. RESULTS: Adult, but not adolescent, dcc, unc5c and netrin-1 haploinsufficient mice exhibit blunted behavioral responses to amphetamine. Furthermore, adult dcc, unc5c, and netrin-1 haploinsufficient mice have exaggerated mPFC dopamine concentrations in comparison to their wild-type littermates. Importantly, resilience to amphetamine-induced behavioral activation in all the three mouse models is abolished by selective dopamine depletion in the medial prefrontal cortex. CONCLUSIONS: dcc, unc5c, or netrin-1 haploinsufficiency leads to increased dopamine content in the mPFC and to resilience against amphetamine-induced behavioral activation. Our findings raise the hypothesis that DCC, UNC5C, and netrin-1 act in concert to organize the adolescent development of mesocortical dopamine innervation and, in turn, determine behavioral responses to drugs of abuse. PMID- 26264904 TI - Facilitation of spatial working memory performance following intra-prefrontal cortical administration of the adrenergic alpha1 agonist phenylephrine. AB - RATIONALE: Spatial working memory is dependent on the appropriate functioning of the prefrontal cortex (PFC). PFC activity can be modulated by noradrenaline (NA) released by afferent projections from the locus coeruleus. The coreuleo-cortical NA system could therefore be a target for cognitive enhancers of spatial working memory. Of the three classes of NA receptor potentially involved, the alpha2 and alpha1 classes seem most significant, though agents targeting these receptors have yielded mixed results. This may be partially due to the use of behavioural assays that do not translate effectively from the laboratory to the clinical setting. Use of a paradigm with improved translational potential may be essential to resolve these discrepancies. OBJECTIVES: The objective of this study was to assess the effects of PFC-infused alpha2 and alpha1 adrenergic receptor agonists on spatial working memory performance in the touchscreen continuous trial-unique non-matching to location (cTUNL) task in rats. METHODS: Young male rats were trained in the cTUNL paradigm. Cannulation of the mPFC allowed direct administration of GABA agonists for task validation, and phenylephrine and guanfacine to determine the effects of adrenergic agonists on task performance. RESULTS: Infusion of muscimol and baclofen resulted in a delay-dependent impairment. Administration of the alpha2 agonist guanfacine had no effect, whilst infusion of the alpha1 agonist phenylephrine significantly improved working memory performance. CONCLUSIONS: Spatial working memory as measured in the rat cTUNL task is dependent on the mPFC. Enhancement of noradrenergic signalling enhanced performance in this paradigm, suggesting a significant role for the alpha1 receptor in this facilitation. PMID- 26264906 TI - Association of CYP2C19, CYP3A5 and GPIIb/IIIa gene polymorphisms with Aspirin and Clopidogrel Resistance in a cohort of Indian patients with Coronary Artery Disease. AB - INTRODUCTION: Dual antiplatelet therapy with clopidogrel and aspirin is the current standard of care in the management of patients with coronary artery disease (CAD) and acute coronary syndrome (ACS). The variability in response to these antiplatelet agents may be due to the underlying genetic diversity. This study was designed to determine the resistance to aspirin and clopidogrel in Indian patients and to look for correlation, if any, with selected polymorphisms. METHODS: Platelet function testing by light transmission aggregometry was performed on 72 patients with CAD/ACS who were stable on dual antiplatelet therapy (clopidogrel 75 mg OD and aspirin 150 mg OD) along with 72 controls. Aspirin resistance was considered as mean platelet aggregation >= 70% with 10 MUm ADP and >= 20% with 0.75 mm arachidonic acid. Clopidogrel resistance was defined as <10% decrease from the baseline in platelet aggregation in response to ADP 10 MUm and semi-response as <30% decrease from the baseline. Polymorphisms CYP2C19*2, *3, CYP3A5*3 and PLA1/A2 were genotyped. RESULTS: We found 51.4% patients with inadequate response to clopidogrel (1.4% resistant and 50% semi responders) and 5.5% patients semi-responders to aspirin, none being completely resistant. The genotype and allele frequencies of CYP2C19*2 and PLA1/A2 gene polymorphisms were significantly different between clopidogrel semi-responders and responders. Carriers of CYP2C19*2 and CYP3A5*3 showed diminished inhibition of platelet aggregation. No significant correlation was found between coronary events, type of coronary intervention with clopidogrel nonresponsiveness. CONCLUSION: Unlike aspirin, a high proportion of partial responders to clopidogrel were identified. In an interim analysis on 72 Indian patients, a significant association was found between CYP2C19*2 and PLA1/A2 in clopidogrel semi-responders. PMID- 26264905 TI - Pituitary adenylate cyclase-activating polypeptide induces a depressive-like phenotype in rats. AB - BACKGROUND: Major depressive disorder (MDD) is a chronic, life-threatening psychiatric condition characterized by depressed mood, psychomotor alterations, and a markedly diminished interest or pleasure in most activities known as anhedonia. Available pharmacotherapies have limited success and the need for new strategies is clear. Recent studies attribute a major role to the pituitary adenylate cyclase-activating polypeptide (PACAP) system in mediating the response to stress. PACAP knockout mice display profound alterations in depressive-like behaviors, and genetic association studies have demonstrated that genetic variants of the PACAP gene are associated with MDD. However, the effects of PACAP administration on depressive-like behaviors in rodents have not yet been systematically examined. OBJECTIVES: The present study investigated the effects of central administration of PACAP in rats on depressive-like behaviors, using well-established animal models that represent some of the endophenotypes of depression. METHODS: We used intracranial self-stimulation (ICSS) to assess the brain reward function, saccharin preference test to assess anhedonia, social interaction to assess social withdrawal, and forced swim test (FST) to assess behavioral despair. RESULTS: PACAP raised the current threshold for ICSS, elevation blocked by the PACAP antagonist PACAP(6-38). PACAP reduced the preference for a sweet saccharin solution and reduced the time the rats spent interacting with a novel animal. Interestingly, PACAP administration did not affect immobility in the FST. CONCLUSIONS: Our results demonstrate a role for the central PACAP/PAC1R system in the regulation of depressive-like behaviors and suggest that hyperactivity of the PACAP/PAC1R system may contribute to the pathophysiology of depression, particularly the associated anhedonic symptomatology and social dysfunction. PMID- 26264907 TI - The Willow Hill Community Health Assessment: Assessing the Needs of Children in a Former Slave Community. AB - The overall purpose of this community needs assessment was to explore the perceptions of health and educational needs among youth residing in a rural Georgia community, document existing assets that could be utilized to meet those needs, and to identify socioeconomic barriers and facilitators in health education. A sequential mixed method design was used. Intercept surveys were conducted followed by individual, key informant interviews and a focus group. Survey data was entered into an Excel spreadsheet and SPSS for analysis and descriptive statistics including means and frequencies were calculated. For qualitative interviews, full transcripts were created from audio-recordings and uploaded into NVivo for content analysis. Several health issues were highlighted by the Willow Hill/Portal Georgia community members, including teachers, parents, youth and Willow Hill Heritage and Renaissance Center board members. Some of the health issues identified by youth in the community were low levels of physical activity, obesity, diabetes, lack of healthy food choices, and access to health care services. Including the issues identified by youth, the parents, teachers and board members identified additional health issues in the community such as asthma, hygiene and lack of dental and eye care facilities. Overall, there is a need for better infrastructure and awareness among community members. Utilizing identified assets, including active community leaders, involved faith-based organizations, commitment of community members, presence of land resources, and commitment to physical activity and sports, could modify the current community landscape. PMID- 26264909 TI - The 21st century cures act: Opportunities and challenges. AB - On July 10, 2015, the U.S. House of Representatives overwhelmingly voted (344-77) to approve the 21st Century Cures Act, setting the stage for the Senate to consider its own version of the bill this fall. Such strong bipartisan support, rare in an age of congressional gridlock, might logically be interpreted as a sign of the Act's promise to foster innovative drug and device development. However, careful inspection reveals that while the Act contains some positive features, it represents a poor deal for Americans on balance that could result in the entry of more dangerous and ineffective drugs and devices onto the market and erode trust in the US Food and Drug Administration (FDA). PMID- 26264908 TI - Pre-clinical evaluation of a minimally invasive laryngeal pacemaker system in mini-pig. AB - Microlaryngoscopic enlargement techniques have been the standard treatment for bilateral vocal fold paralysis (BVFP) for decades. Laryngeal pacing is a promising alternative treatment based on the electrostimulation of the posterior cricoarytenoid (PCA) muscle. This paper reports on the results of a pre-clinical study aiming to evaluate this method. Eight Gottingen mini-pigs were implanted with a laryngeal pacemaker (LP) implant prototype and with two LP electrodes, one in each PCA muscle. The 6-week follow-up included endoscopic stimulation controls in general anaesthesia and radiographic controls of electrode integrity and position stability. Stimulation parameters for optimal glottal opening were evaluated via videolaryngoscopy. Histopathology was performed upon conclusion of the study. 7/8 (87.5 %) animals were successfully implanted with the LP implant prototype and two LP electrodes. In general, stimulation was effectively delivered and correlated with the expected PCA muscle activation. 2/14 (14.3 %) electrodes dislocated and 1/14 (7.1 %) electrode tip broke. The LP system used in this experiment to induce vocal fold abduction by means of selective functional electrical stimulation of the PCA showed promising results. It may be a valid alternative to the current golden standard for BVFP treatment. Clinical studies are needed to confirm the medical relevance of the LP. PMID- 26264910 TI - Caloric restriction increases ratio of estrogen to androgen receptors expression in murine ovaries--potential therapeutic implications. AB - Both estrogens and androgens are involved in the development and normal functioning of the ovaries. It is also known that ovarian function is regulated by diet. The goal of this study was to estimate the expression of sex hormone receptors in ovaries of mice that were on a 9-month caloric restriction (alternate-day feeding) as compared to normal control animals fed ad libitum. We found that prolonged caloric restriction in mouse ovaries led to increased expression of estrogen receptors (ERs) but did not affect expression of the androgen receptor (AR). This increase in ER:AR ration as result of caloric restriction may lead to higher sensitivity to estrogens and upon return to normal diet may increase ovulation. Thus our observation shed more light on a role of beneficial effect of calorie restriction on female reproduction. PMID- 26264911 TI - Differences between multimedia and text-based assessments of emotion management: An exploration with the multimedia emotion management assessment (MEMA). AB - People process emotional information using visual, vocal, and verbal cues. However, emotion management is typically assessed with text based rather than multimedia stimuli. This study (N = 427) presents the new multimedia emotion management assessment (MEMA) and compares it to the text-based assessment of emotion management used in the MSCEIT. The text-based and multimedia assessment showed similar levels of cognitive saturation and similar prediction of relevant criteria. Results demonstrate that the MEMA scores have equivalent evidence of validity to the text-based MSCEIT test scores, demonstrating that multimedia assessment of emotion management is viable. Furthermore, our results inform the debate as to whether cognitive saturation in emotional intelligence (EI) measures represents "noise" or "substance". We find that cognitive ability associations with EI represent substantive variance rather than construct-irrelevant shared variance due to reading comprehension ability required for text-based items. PMID- 26264912 TI - Simultaneous determination of nucleoside and purine compounds in human urine based on a hydrophobic monolithic column using capillary electrochromatography. AB - A novel capillary electrochromatography method was developed by using a polymethacrylate ester based monolithic column for the simultaneous separation and determination of five nucleoside and purine compounds in urine. The porous monolithic column was first designed by mean of in situ copolymerizing stearyl methacrylate, trihydroxymethylpropyl trimethylacrylate, and 2-acrylamido-2-methyl 1-propanesulfonic acid in a ternary porogenic solvent including cyclohexanol, 1,4 butanediol, and water. The performance and influence factors of the monolithic columns were investigated and evaluated by a CEC method. The five compounds including guanine, adenine, adenosine, cytidine, and N6 -methyladenosine were selected as analytes. Under the optimized condition of 6.0 mM phosphate buffer at pH 5.0 without ACN, five analytes were rapidly separated in 4 min with the high separation efficiency. The recoveries of spiked samples were ranged from 89.0 to 109.0% with RSDs less than 4.83%. Therefore, the proposed method could possibly provide for rapid separation and detection of the nucleoside and purine compounds in biomedicine sample. PMID- 26264913 TI - A systematic, realist review of zooprophylaxis for malaria control. AB - BACKGROUND: Integrated vector management (IVM) is recommended as a sustainable approach to malaria control. IVM consists of combining vector control methods based on scientific evidence to maximize efficacy and cost-effectiveness while minimizing negative impacts, such as insecticide resistance and environmental damage. Zooprophylaxis has been identified as a possible component of IVM as livestock may draw mosquitoes away from humans, decreasing human-vector contact and malaria transmission. It is possible, however, that livestock may actually draw mosquitoes to humans, increasing malaria transmission (zoopotentiation). The goal of this paper is to take a realist approach to a systematic review of peer reviewed literature to understand the contexts under which zooprophylaxis or zoopotentiation occur. METHODS: Three electronic databases were searched using the keywords 'zooprophylaxis' and 'zoopotentiation', and forward and backward citation tracking employed, to identify relevant articles. Only empirical, peer reviewed articles were included. Critical appraisal was applied to articles retained for full review. RESULTS: Twenty empirical studies met inclusion criteria after critical appraisal. A range of experimental and observational study designs were reported. Outcome measures included human malaria infection and mosquito feeding behaviour. Two key factors were consistently associated with zooprophylaxis and zoopotentiation: the characteristics of the local mosquito vector, and the location of livestock relative to human sleeping quarters. These associations were modified by the use of bed nets and socio-economic factors. DISCUSSION: This review suggests that malaria risk is reduced (zooprophylaxis) in areas where predominant mosquito species do not prefer human hosts, where livestock are kept at a distance from human sleeping quarters at night, and where mosquito nets or other protective measures are used. Zoopotentiation occurs where livestock are housed within or near human sleeping quarters at night and where mosquito species prefer human hosts. CONCLUSION: The evidence suggests that zooprophylaxis could be part of an effective strategy to reduce malaria transmission under specific ecological and geographical conditions. The current scientific evidence base is inconclusive on understanding the role of socio economic factors, optimal distance between livestock and human sleeping quarters, and the effect of animal species and number on zooprophylaxis. PMID- 26264915 TI - SOD1 deficiency decreases proteasomal function, leading to the accumulation of ubiquitinated proteins in erythrocytes. AB - We previously demonstrated that elevated levels of ROS in red blood cells (RBCs) are responsible for anemia in SOD1-deficient mice, suggesting that the oxidative stress-induced massive destruction of RBCs is an underlying mechanism for autoimmune hemolytic anemia. In the current study, we examined the issue of how elevated ROS are involved in the destruction of RBCs and the onset of anemia from the view point of the proteolytic removal of oxidatively-damaged proteins. We found that poly-ubiquitinated proteins had accumulated and had undergone aggregation in RBCs from SOD1-deficient mice and from phenylhydrazine-induced anemic mice. Although the protein levels of the three catalytic components of the proteasome, beta1, beta2, and beta5, were not significantly altered, their proteolytic activities were decreased in the SOD1-deficient RBCs. These data suggest that oxidative-stress triggers the dysfunction of the proteasomal system, which results in the accumulation of the aggregation of poly-ubiquitinated proteins. We conclude that an oxidative stress-induced malfunction in the scavenging activity of proteasomes accelerates the accumulation of damaged proteins, leading to a shortened lifespan of RBCs and, hence, anemia. PMID- 26264916 TI - Expression and characterization of manganese lipoxygenase of the rice blast fungus reveals prominent sequential lipoxygenation of alpha-linolenic acid. AB - Magnaporthe oryzae causes rice blast disease and has become a model organism of fungal infections. M. oryzae can oxygenate fatty acids by 7,8-linoleate diol synthase, 10R-dioxygenase-epoxy alcohol synthase, and by a putative manganese lipoxygenase (Mo-MnLOX). The latter two are transcribed during infection. The open reading frame of Mo-MnLOX was deduced from genome and cDNA analysis. Recombinant Mo-MnLOX was expressed in Pichia pastoris and purified to homogeneity. The enzyme contained protein-bound Mn and oxidized 18:2n-6 and 18:3n 3 to 9S-, 11-, and 13R-hydroperoxy metabolites by suprafacial hydrogen abstraction and oxygenation. The 11-hydroperoxides were subject to beta fragmentation with formation of 9S- and 13R-hydroperoxy fatty acids. Oxygen consumption indicated apparent kcat values of 2.8 s(-1) (18:2n-6) and 3.9 s(-1) (18:3n-3), and UV analysis yielded apparent Km values of 8 and 12 MUM, respectively, for biosynthesis of cis-trans conjugated metabolites. 9S Hydroperoxy-10E,12Z,15Z-octadecatrienoic acid was rapidly further oxidized to a triene, 9S,16S-dihydroperoxy-10E,12Z,14E-octadecatrienoic acid. In conclusion, we have expressed, purified and characterized a new MnLOX from M. oryzae. The pathogen likely secretes Mo-MnLOX and phospholipases to generate oxylipins and to oxidize lipid membranes of rice cells and the cuticle. PMID- 26264917 TI - Quality assurance in the pre-analytical phase of human urine samples by (1)H NMR spectroscopy. AB - Metabolomic approaches investigate changes in metabolite profiles, which may reflect changes in metabolic pathways and provide information correlated with a specific biological process or pathophysiology. High-resolution (1)H NMR spectroscopy is used to identify metabolites in biofluids and tissue samples qualitatively and quantitatively. This pre-analytical study evaluated the effects of storage time and temperature on (1)H NMR spectra from human urine in two settings. Firstly, to evaluate short time effects probably due to acute delay in sample handling and secondly, the effect of prolonged storage up to one month to find markers of sample miss-handling. A number of statistical procedures were used to assess the differences between samples stored under different conditions, including Projection to Latent Structure Discriminant Analysis (PLS-DA), non parametric testing as well as mixed effect linear regression analysis. The results indicate that human urine samples can be stored at 10 degrees C for 24 h or at -80 degrees C for 1 month, as no relevant changes in (1)H NMR fingerprints were observed during these time periods and temperature conditions. However, some metabolites most likely of microbial origin showed alterations during prolonged storage but without facilitating classification. In conclusion, the presented protocol for urine sample handling and semi-automatic metabolite quantification is suitable for large-scale epidemiological studies. PMID- 26264918 TI - Assessment of collagen crosslinking and denaturation for the design of regenerative scaffolds. AB - Crosslinking and denaturation were two variables that deeply affected the performance of collagen-based scaffolds designed for tissue regeneration. If crosslinking enhances the mechanical properties and the enzymatic resistance of collagen, while masking or reducing the available cell binding sites, denaturation has very opposite effects, as it impairs the mechanical and the enzymatic stability of collagen, but increases the number of exposed cell adhesive domains. The quantification of both crosslinking and denaturation was thus fundamental to the design of collagen-based scaffolds for selected applications. The aim of this work was to investigate the extents of crosslinking and denaturation of collagen-based films upon dehydrothermal (DHT) treatment, that is, one of the most commonly employed methods for zero-length crosslinking that shows the unique ability to induce partial denaturation. Swelling measurements, differential scanning calorimetry, Fourier transform infrared spectroscopy, colorimetric assays for the quantification of primary amines, and mechanical tests were performed to analyze the effect of the DHT temperature on crosslinking and denaturation. In particular, chemically effective and elastically effective crosslink densities were evaluated. Both crosslinking and denaturation were found to increase with the DHT temperature, although according to different trends. The results also showed that DHT treatments performed at temperatures up to 120 degrees C maintained the extent of denaturation under 25%. Coupling a mild DHT treatment with further crosslinking may thus be very useful not only to modulate the crosslink density, but also to induce a limited amount of denaturation, which shows potential to partially compensate the loss of cell binding sites caused by crosslinking. PMID- 26264914 TI - Molecular Targets of Cannabidiol in Neurological Disorders. AB - Cannabis has a long history of anecdotal medicinal use and limited licensed medicinal use. Until recently, alleged clinical effects from anecdotal reports and the use of licensed cannabinoid medicines are most likely mediated by tetrahydrocannabinol by virtue of: 1) this cannabinoid being present in the most significant quantities in these preparations; and b) the proportion:potency relationship between tetrahydrocannabinol and other plant cannabinoids derived from cannabis. However, there has recently been considerable interest in the therapeutic potential for the plant cannabinoid, cannabidiol (CBD), in neurological disorders but the current evidence suggests that CBD does not directly interact with the endocannabinoid system except in vitro at supraphysiological concentrations. Thus, as further evidence for CBD's beneficial effects in neurological disease emerges, there remains an urgent need to establish the molecular targets through which it exerts its therapeutic effects. Here, we conducted a systematic search of the extant literature for original articles describing the molecular pharmacology of CBD. We critically appraised the results for the validity of the molecular targets proposed. Thereafter, we considered whether the molecular targets of CBD identified hold therapeutic potential in relevant neurological diseases. The molecular targets identified include numerous classical ion channels, receptors, transporters, and enzymes. Some CBD effects at these targets in in vitro assays only manifest at high concentrations, which may be difficult to achieve in vivo, particularly given CBD's relatively poor bioavailability. Moreover, several targets were asserted through experimental designs that demonstrate only correlation with a given target rather than a causal proof. When the molecular targets of CBD that were physiologically plausible were considered for their potential for exploitation in neurological therapeutics, the results were variable. In some cases, the targets identified had little or no established link to the diseases considered. In others, molecular targets of CBD were entirely consistent with those already actively exploited in relevant, clinically used, neurological treatments. Finally, CBD was found to act upon a number of targets that are linked to neurological therapeutics but that its actions were not consistent withmodulation of such targets that would derive a therapeutically beneficial outcome. Overall, we find that while >65 discrete molecular targets have been reported in the literature for CBD, a relatively limited number represent plausible targets for the drug's action in neurological disorders when judged by the criteria we set. We conclude that CBD is very unlikely to exert effects in neurological diseases through modulation of the endocannabinoid system. Moreover, a number of other molecular targets of CBD reported in the literature are unlikely to be of relevance owing to effects only being observed at supraphysiological concentrations. Of interest and after excluding unlikely and implausible targets, the remaining molecular targets of CBD with plausible evidence for involvement in therapeutic effects in neurological disorders (e.g., voltage-dependent anion channel 1, G protein-coupled receptor 55, CaV3.x, etc.) are associated with either the regulation of, or responses to changes in, intracellular calcium levels. While no causal proof yet exists for CBD's effects at these targets, they represent the most probable for such investigations and should be prioritized in further studies of CBD's therapeutic mechanism of action. PMID- 26264920 TI - Mycobacterium tuberculosis Low Molecular Weight Phosphatases (MPtpA and MPtpB): From Biological Insight to Inhibitors. AB - Mycobacterium tuberculosis (Mtb), the main aetiological agent of tuberculosis (TB) in humans, is estimated to cause nearly two million deaths every year. Despite their huge therapeutic value, existing antitubercular drugs have several shortcomings, such as for instance the insurgence of drug resistance, which is mostly triggered by lack of compliance during the lengthy treatment. Novel and more effective drugs against Mtb acting on new molecular targets are therefore in demand in order to reduce treatment time and address the severe issue related to the progressive loss of antibiotic efficacy. Mtb encodes for two low molecular weight tyrosine specific phosphatases (MPtpA and MPtpB) that are crucially involved in Mtb pathogenesis. While MPtpA interferes with phagosome acidification blocking its maturation, MPtpB disrupts host signal transduction cascades, causing immune response subversion in the host. The important role played by both MPtpA and MPtpB in host-pathogen interaction makes them appealing targets for TB drug discovery. Here, we provide an exhaustive review of the current knowledge on MPtpA and MPtpB characterization and role in TB pathogenesis. In particular, special emphasis is placed on all class of inhibitors that have been developed and studied to date; their binding mode, design strategies, biological activities, main pharmacophore features as well as the efforts to overcome the poor druggability of their target are summarized in detail. PMID- 26264921 TI - From Bitopic Inhibitors to Multitarget Drugs for the Future Treatment of Alzheimer's Disease. AB - Dementia is one of the main causes of the disease burden in developed regions. According to the World Health Organization (WHO), it will become the world's second leading cause of death by the middle of the century, overtaking cancer. This will have a dramatic impact on medical care, and have important social and economic implications, unless more effective preventive procedures or treatments become available. Alzheimer's disease (AD) is the most common cause of dementia, accounting for approximately 50-75% of all dementias worldwide, followed by vascular dementia, mixed dementia, and Lewy body dementia. Currently, acetylcholinesterase (AChE) inhibitors, such as donepezil, rivastigmine and galantamine are used to treat mild to moderate AD. An alternative therapy for severe AD is memantine, an antagonist of the NMDA-subtype of glutamate receptors. However, these drugs provide only temporary symptom improvement, and do not alter disease progression, except temporarily in some patients. In recent years different approaches have been developed to provide a more effective treatment for AD. These approached include the discovery of emerging targets and new drugs aiming at a single target, but given the complexity of the disease, different targets may need to be engaged simultaneously. New strategies have explored bitopic inhibitors, for example a single drug that acts on different sites of the acetylcholinesterase enzyme to produce at least two different activities, and multitarget drugs that act on multiple therapeutic targets. In this review, we explore the journey from a bitopic inhibitor strategy to multitarget drugs for the future treatment of AD. PMID- 26264922 TI - Progress in the Search for New Dopamine Transporter Inhibitors. AB - In the present review, we provide a comprehensive summary of recent pharmacological studies on dopamine transporter (DAT) inhibitors, which are potential treatments for neurodegenerative and psychiatric disorders. Extensive structure-activity relationship studies have identified numerous tropane-based ligands with high affinity and selectivity for the DAT or with high affinity to the DAT and other monoamine transporters (dual and triple monoamine reuptake inhibitors). The review covers advances in the field in past fifteen years. Among the described compounds, many appear to be promising drug candidates, while other may serve as valuable tools for research or as prototypes for new classes of selective DAT inhibitors. Special attention is being paid to separation of the DAT inhibition from NET and SERT inhibition. PMID- 26264919 TI - Extracellular volume quantification in isolated hypertension - changes at the detectable limits? AB - BACKGROUND: Diffuse myocardial fibrosis (DMF) is important in cardiovascular disease, however until recently could only be assessed by invasive biopsy. We hypothesised that DMF measured by T1 mapping is elevated in isolated systemic hypertension. METHODS: In a study of well-controlled hypertensive patients from a specialist tertiary centre, 46 hypertensive patients (median age 56, range 21 to 78, 52 % male) and 50 healthy volunteers (median age 45, range 28 to 69, 52 % male) underwent clinical CMR at 1.5 T with T1 mapping (ShMOLLI) using the equilibrium contrast technique for extracellular volume (ECV) quantification. Patients underwent 24-hours Automated Blood Pressure Monitoring (ABPM), echocardiographic assessment of diastolic function, aortic stiffness assessment and measurement of NT-pro-BNP and collagen biomarkers. RESULTS: Late gadolinium enhancement (LGE) revealed significant unexpected underlying pathology in 6 out of 46 patients (13 %; myocardial infarction n = 3; hypertrophic cardiomyopathy (HCM) n = 3); these were subsequently excluded. Limited, non-ischaemic LGE patterns were seen in 11 out of the remaining 40 (28 %) patients. Hypertensives on therapy (mean 2.2 agents) had a mean ABPM of 152/88 mmHg, but only 35 % (14/40) had left ventricular hypertrophy (LVH; LV mass male > 90 g/m(2); female > 78 g/m(2)). Native myocardial T1 was similar in hypertensives and controls (955 +/- 30 ms versus 965 +/- 38 ms, p = 0.16). The difference in ECV did not reach significance (0.26 +/- 0.02 versus 0.27 +/- 0.03, p = 0.06). In the subset with LVH, the ECV was significantly higher (0.28 +/- 0.03 versus 0.26 +/- 0.02, p < 0.001). CONCLUSION: In well-controlled hypertensive patients, conventional CMR discovered significant underlying diseases (chronic infarction, HCM) not detected by echocardiography previously or even during this study. T1 mapping revealed increased diffuse myocardial fibrosis, but the increases were small and only occurred with LVH. PMID- 26264923 TI - Quercetin in Cancer Treatment, Alone or in Combination with Conventional Therapeutics? AB - Cancer is a problem of global importance, since the incidence is increasing worldwide and therapeutic options are generally limited. Thus, it becomes imperative to find new therapeutic targets as well as new molecules with therapeutic potential for tumors. Flavonoids are polyphenolic compounds that may be potential therapeutic agents. Several studies have shown that these compounds have a higher anticancer potential. Among the flavonoids in the human diet, quercetin is one of the most important. In the last decades, several anticancer properties of quercetin have been described, such as cell signaling, pro apoptotic, anti-proliferative and anti-oxidant effects, growth suppression. In fact, it is now well known that quercetin has diverse biological effects, inhibiting multiple enzymes involved in cell proliferation, as well as, in signal transduction pathways. On the other hand, there are also studies reporting potential synergistic effects when combined quercetin with chemotherapeutic agents or radiotherapy. In fact, several studies which aim to explore the anticancer potential of these combined treatments have already been published, the majority with promising results. Actually it is well known that quercetin can act on the chemosensitization and radiosensitization but also as chemoprotective and radioprotective, protecting normal cells of the side effects that results from chemotherapy and radiotherapy, which obviously provides notable advantages in their use in anticancer treatment. Thus, all these data indicate that quercetin may have a key role in anticancer treatment. In this context, this review is focused on the relationship between flavonoids and cancer, with special emphasis on the role of quercetin. PMID- 26264924 TI - Role of Serum and Glucocorticoid-Inducible Kinase (SGK)-1 in Senescence: A Novel Molecular Target Against Age-Related Diseases. AB - Senescence is a phenomenon characterized by a progressive decline of body homeostasis. Premature senescence acts when the cellular system is not able to adequately respond to noxious stimuli by synthesis of stressor molecules. Among those, serum-and-glucocorticoidinducible kinase-1 (SGK-1) dramatically increases under typical physiopathological conditions, such as glucocorticoid or mineralcorticoids exposure, inflammation, hyperglycemia, and ischemia. SGK-1 has been implicated in mechanism regulating oxidative stress, apoptosis, and DNA damage, which are all leading to a state of accelerating aging. Moreover, SGK-1 sensitive ion channels participate in the regulation of renal Na(+)/K(+) regulation, blood pressure, gastric acid secretion, cardiac action potential, and neuroexcitability. Recently, we demonstrated in endothelial cells as an increase in SGK-1 activity and expression reduces oxidative stress, improves cell survival and restores insulin-mediated nitric oxide production after hyperglycemia. Moreover, we showed as SGK-1 delays the onset of senescence by increasing telomerase activity, significantly decreasing reactive oxygen species (ROS) production, and by directly interacting with hTERT. Therefore, SGK-1 may represent a specific target to further develop novel therapeutic options against chronic diseases such as diabetes typical of aging. SGK-1 has been also associated with cancer, neurodegenerative diseases, and cardiovascular disease, among other age-related diseases. However, to date, the data available on SGK-1 and aging, are sparse, controversial, and only from C. elegans experimental models. In this review we sought to discuss the possible implication of SGK-1 in mechanisms regulating senescence and age-related diseases. Moreover, we aimed to discuss and identify the possible role of SGK-1 as possible molecular target to counteract and prevent aging. PMID- 26264925 TI - Quinoxalines Potential to Target Pathologies. AB - The study of quinoxalines has increased immeasurably during the last two decades, due firstly to their relatively simple chemical synthesis, which has generated a vast variety of compounds with diverse structural modifications, and secondly, to the wide therapeutic potential and biological activities exhibited by this family of compounds. Quinoxalines constitute a rising biomedical class of low-molecular weight heterocyclic compounds with potential functions as antitumour, anti inflammatory, antibacterial, antiviral, antifungal, antiparasitic and antidiabetic agents, as well as being of interest for the potential treatment of glaucoma, insomnia, cardiovascular and neurological diseases, among others. However, a deeper knowledge of the molecular targets of quinoxalines that fulfil a key role in certain pathologies is required for the development of new and more specific drugs through a rational design strategy to avoid undesirable side effects. In the present review, we summarize the most important molecular targets of the quinoxaline derivatives discovered to date, thus providing a first reference index for researchers to identify the potential targets of their quinoxalines derived collections, which could facilitate the development of new quinoxaline- based therapies. PMID- 26264926 TI - Production of Y-86 and other radiometals for research purposes using a solution target system. AB - INTRODUCTION: Diagnostic radiometals are typically obtained from cyclotrons by irradiating solid targets or from radioisotope generators. These methods have the advantage of high production yields, but require additional solid target handling infrastructure that is not readily available to many cyclotron facilities. Herein, we provide an overview of our results regarding the production of various positron-emitting radiometals using a liquid target system installed on a 13 MeV cyclotron at TRIUMF. Details about the production, purification and quality control of (89)Zr, (68)Ga and for the first time (86)Y are discussed. METHODS: Aqueous solutions containing 1.35-1.65 g/mL of natural-abundance zinc nitrate, yttrium nitrate, and strontium nitrate were irradiated on a 13 MeV cyclotron using a standard liquid target. Different target body and foil materials were investigated for corrosion. Production yields were calculated using theoretical cross-sections from the EMPIRE code and compared with experimental results. The radioisotopes were extracted from irradiated target material using solid phase extraction methods adapted from previously reported methods, and used for radiolabelling experiments. RESULTS: We demonstrated production quantities that are sufficient for chemical and biological studies for three separate radiometals, (89)Zr (Asat = 360 MBq/MUA and yield = 3.17 MBq/MUA), (86)Y (Asat = 31 MBq/MUA and yield = 1.44 MBq/MUA), and (68)Ga (Asat = 141 MBq/MUA and yield = 64 MBq/MUA) from one hour long irradiations on a typical medical cyclotron. (68)Ga yields were sufficient for potential clinical applications. In order to avoid corrosion of the target body and target foil, nitrate solutions were chosen as well as niobium as target-body material. An automatic loading system enabled up to three production runs per day. The separation efficiency ranged from 82 to 99%. Subsequently, (68)Ga and (86)Y were successfully used to radiolabel DOTA based chelators while deferoxamine was used to coordinate (89)Zr. PMID- 26264927 TI - PET-CT imaging with [(18)F]-gefitinib to measure Abcb1a/1b (P-gp) and Abcg2 (Bcrp1) mediated drug-drug interactions at the murine blood-brain barrier. AB - INTRODUCTION: The efflux transporters P-glycoprotein (P-gp, ABCB1) and breast cancer resistance protein (BCRP, ABCG2) are expressed at the blood-brain barrier (BBB), and can limit the access of a wide range of drugs to the brain. In this study we developed a PET-CT imaging method for non-invasive, quantitative analysis of the effect of ABCB1 and ABCG2 on brain penetration of the anti-cancer drug gefitinib, and demonstrated the applicability of this method for identification and quantification of potential modulators of ABCB1 and ABCB2 using the dual inhibitor elacridar. METHODS: In vitro cellular accumulation studies with [(14)C]-gefitinib were conducted in LLC-PK1, MDCKII, and the corresponding ABCB1/Abcb1a and ABCG2/Abcg2 overexpressing cell lines. Subsequently, in vivo brain penetration of [(18)F]-gefitinib was quantified by PET-CT imaging studies in wild-type, Abcg2(-/-), Abcb1a/1b(-/-), and Abcb1a/1b;Abcg2(-/-) mice. RESULTS: In vitro studies showed that [(14)C] gefitinib is a substrate of the human ABCB1 and ABCG2 transporters. After i.v. administration of [(18)F]-gefitinib (1mg/kg), PET-CT imaging showed 2.3-fold increased brain levels of [(18)F]-gefitinib in Abcb1a/1b;Abcg2(-/-) mice, compared to wild-type. Levels in single knockout animals were not different from wild-type, showing that Abcb1a/1b and Abcg2 together limit access of [(18)F] gefitinib to the brain. Furthermore, enhanced brain accumulation of [(18)F] gefitinib after administration of the ABCB1 and ABCG2 inhibitor elacridar (10 mg/kg) could be quantified with PET-CT imaging. CONCLUSIONS: PET-CT imaging with [(18)F]-gefitinib is a powerful tool to non-invasively assess potential ABCB1- and ABCG2-mediated drug-drug interactions (DDIs) in vivo. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: This minimally-invasive, [(18)F]-based PET-CT imaging method shows the interplay of ABCB1 and ABCG2 at the BBB in vivo. The method may be applied in the future to assess ABCB1 and ABCG2 activity at the BBB in humans, and for personalized treatment with drugs that are substrates of ABCB1 and/or ABCG2. PMID- 26264928 TI - Towards the commercialization of Botryococcus braunii for triterpenoid production. AB - Botryococcus braunii can accumulate unusually high levels of triterpenoid hydrocarbons making it a potential source of high value chemicals. However, its commercial application is hampered by its slow growth and lack of large-scale studies of triterpenoid hydrocarbon production. This study investigated hydrocarbon production in two race B of B. braunii strains, Overjuyo-3 and Kossou 4, at 25 degrees C in 500 L open tanks under artificial lighting in modified BG11 medium over 60 days. Maximum growth was reached by 40 days with Overjuyo-3 producing more biomass (3.05 g L(-1)) than Kossou-4 (2.55 g L(-1)). However, Kossou-4 produced more oil (0.75 g L(-1)) and triterpenoid hydrocarbons (C30-C34; 50 % of oil weight) compared to 0.63 g L(-1) of oil in Overjuyo-3 with triterpenoid hydrocarbons making up 29 % of oil weight. This research demonstrates for the first time that large-scale production of high value triterpenoid hydrocarbon for commercial application is feasible with Kossou-4 strain. PMID- 26264929 TI - Model-based evaluation of ferrous iron oxidation by acidophilic bacteria in chemostat and biofilm airlift reactors. AB - This article presents a model-based evaluation of ferrous iron oxidation in chemostat and biofilm airlift reactors inoculated with a mixed culture of Acidithiobacillus ferrooxidans and Leptospirillum ferrooxidans bacteria. The competition between the two types of bacteria in the chemostat and in the biofilm airlift reactors together with the distribution of both bacteria along the biofilm thickness at different time sections has been studied. The bacterial distribution profiles along the biofilm in the airlift reactor at different time scales show that in the beginning A. ferrooxidans bacteria are dominant, but when the reactor operates for a long time the desirable L. ferrooxidans species outcompete A. ferrooxidans as a result of the low Fe(2+) and high Fe(3+) concentrations. The results obtained from the simulation were compared with the experimental data of continuously operated internal loop airlift biofilm reactor. The model results are in good agreement with the experimental results. PMID- 26264930 TI - Bioprocess for efficient production of recombinant Pichia anomala phytase and its applicability in dephytinizing chick feed and whole wheat flat Indian breads. AB - The phytase of the yeast Pichia anomala (PPHY) is a suitable biocatalyst as a food and feed additive because of its adequate thermostability, acid stability, protease insensitivity and broad substrate spectrum. The cell-bound nature and low phytase titres are the main bottlenecks for its utility in food and feed industries. In this investigation, we have overcome the problems by constitutive secretory expression of PPHY under glyceraldehyde phosphate dehydrogenase (GAP) promoter. A ~44-fold increase in rPPHY titre has been achieved after optimization of cultural variables by one-variable-at-a-time approach and two factorial statistical design. The use of GAP promoter makes the cultivation of the recombinant P. pastoris straight forward and eliminates the requirement of methanol for induction and hazards associated with its storage. Among metal phytate complexes, Ca(2+) phytate is hydrolyzed more efficiently by rPPHY than Co(2+), Mn(2+), Mg(2+), Fe(3+) and Zn(2+) phytates. The enzyme is effective in dephytinizing whole wheat unleavened flat Indian breads (naan and tandoori) and different broiler feeds, thus mitigating anti-nutritional effects of phytates. PMID- 26264931 TI - Lead recovery from scrap cathode ray tube funnel glass by hydrothermal sulphidisation. AB - This research focused on the application of the hydrothermal sulphidisation method to separate lead from scrap cathode ray tube funnel glass. Prior to hydrothermal treatment, the cathode ray tube funnel glass was pretreated by mechanical activation. Under hydrothermal conditions, hydroxyl ions (OH(-)) were generated through an ion exchange reaction between metal ions in mechanically activated funnel glass and water, to accelerate sulphur disproportionation; no additional alkaline compound was needed. Lead contained in funnel glass was converted to lead sulphide with high efficiency. Temperature had a significant effect on the sulphidisation rate of lead in funnel glass, which increased from 25% to 90% as the temperature increased from 100 degrees C to 300 degrees C. A sulphidisation rate of 100% was achieved at a duration of 8 h at 300 degrees C. This process of mechanical activation and hydrothermal sulphidisation is efficient and promising for the treatment of leaded glass. PMID- 26264932 TI - Comparative biochemical analysis after steam pretreatment of lignocellulosic agricultural waste biomass from Williams Cavendish banana plant (Triploid Musa AAA group). AB - The accessibility of fermentable substrates to enzymes is a limiting factor for the efficient bioconversion of agricultural wastes in the context of sustainable development. This paper presents the results of a biochemical analysis performed on six combined morphological parts of Williams Cavendish Lignocellulosic Biomass (WCLB) after steam cracking (SC) and steam explosion (SE) pretreatments. Solid (S) and liquid (L) fractions (Fs) obtained from SC pretreatment performed at 180 degrees C (SLFSC180) and 210 degrees C (SLFSC210) generated, after diluted acid hydrolysis, the highest proportions of neutral sugar (NS) contents, specifically 52.82 +/- 3.51 and 49.78 +/- 1.39%w/w WCLB dry matter (DM), respectively. The highest proportions of glucose were found in SFSC210 (53.56 +/- 1.33%w/w DM) and SFSC180 (44.47 +/- 0.00%w/w DM), while the lowest was found in unpretreated WCLB (22.70 +/- 0.71%w/w DM). Total NS content assessed in each LF immediately after SC and SE pretreatments was less than 2%w/w of the LF DM, thus revealing minor acid autohydrolysis consequently leading to minor NS production during the steam pretreatment. WCLB subjected to SC at 210 degrees C (SC210) generated up to 2.7 fold bioaccessible glucan and xylan. SC and SE pretreatments showed potential for the deconstruction of WCLB (delignification, depolymerization, decrystallization and deacetylation), enhancing its enzymatic hydrolysis. The concentrations of enzymatic inhibitors, such as 2-furfuraldehyde and 5-(hydroxymethyl)furfural from LFSC210, were the highest (41 and 21 ug ml(-1), respectively). This study shows that steam pretreatments in general and SC210 in particular are required for efficient bioconversion of WCLB. Yet, biotransformation through biochemical processes (e.g., anaerobic digestion) must be performed to assess the efficiency of these pretreatments. PMID- 26264934 TI - Debilitating fatigue as a treatment indication in chronic hepatitis C. PMID- 26264933 TI - Ubiquitin C-terminal hydrolase 1: A novel functional marker for liver myofibroblasts and a therapeutic target in chronic liver disease. AB - BACKGROUND & AIMS: Ubiquitination is a reversible protein modification involved in the major cellular processes that define cell phenotype and behaviour. Ubiquitin modifications are removed by a large family of proteases named deubiquitinases. The role of deubiquitinases in hepatic stellate cell (HSC) activation and their contribution to fibrogenesis are poorly defined. We have identified that the deubiquitinase ubiquitin C-terminal hydrolase 1 (UCHL1) is highly induced following HSC activation, determined its function in activated HSC and its potential as a therapeutic target for fibrosis. METHODS: Deubiquitinase expression was determined in day 0 and day 10 HSC. Increased UCHL1 expression was confirmed in human HSC and in an alcoholic liver disease (ALD) patient liver. The importance of UCHL1 in hepatic fibrosis was investigated in CCl4 and bile duct ligation injured mice using a pharmacological inhibitor (LDN 57444). The effects of UCHL1 inhibition on HSC proliferation were confirmed by Western blot and 3H thymidine incorporation. RESULTS: Here we report that pharmacological inhibition of UCHL1 blocks progression of established fibrosis in CCl4 injured mice. UCHL1 siRNA knockdown, LDN 57444 treatment, or HSC isolated from UCHL1(-/-) mice show attenuated proliferation in response to the mitogen, platelet-derived growth factor. Additionally, we observed changes in the phosphorylation of the cell cycle regulator retinoblastoma protein (Rb) in the absence of UCHL1 highlighting a potential mechanism for the reduced proliferative response. CONCLUSIONS: UCHL1 expression is highly upregulated upon HSC activation and is involved in the regulation of HSC proliferation. This study highlights therapeutic opportunities for pharmacological targeting of UCHL1 in chronic liver disease. PMID- 26264935 TI - Repurposing of metformin in liver injury: The JNK conundrum. PMID- 26264936 TI - Activation of Slit2-Robo1 signaling promotes liver fibrosis. AB - BACKGROUND & AIMS: The secretory protein Slit2 and its receptor Robo1 are believed to regulate cell growth and migration. Here, we aimed to determine whether Slit2-Robo1 signaling mediates the pathogenesis of liver fibrosis. METHODS: Serum levels of Slit2 in patients with liver fibrosis were determined by ELISA. Liver fibrosis was induced in wild-type (WT), Slit2 transgenic (Slit2-Tg) and Robo1(+/-)Robo2(+/-) double heterozygotes (Robo1/2(+/-)) mice by carbon tetrachloride (CCl4). The functional contributions of Slit2-Robo1 signaling in liver fibrosis and activation of hepatic stellate cells (HSCs) were investigated using primary mouse HSCs and human HSC cell line LX-2. RESULTS: Significantly increased serum Slit2 levels and hepatic expression of Slit2 and Robo1 were observed in patients with liver fibrosis. Compared to WT mice, Slit2-Tg mice were much more vulnerable to CCl4-induced liver injury and more readily develop liver fibrosis. Development of hepatic fibrosis in Slit2-Tg mice was associated with a stronger hepatic expression of collagen I and alpha-smooth muscle actin (alpha SMA). However, liver injury and hepatic expression of collagen I and alpha-SMA were attenuated in CCl4-treated Robo1/2(+/-) mice in response to CCl4 exposure. In vitro, Robo1 neutralizing antibody R5 and Robo1 siRNA downregulated phosphorylation of Smad2, Smad3, PI3K, and AKT in HSCs independent of TGF-beta1. R5 and Robo1 siRNA also inhibited the expression of alpha-SMA by HSCs. Finally, the protective effect of R5 on the CCl4-induced liver injury and fibrosis was further verified in mice. CONCLUSIONS: Slit2-Robo1 signaling promotes liver injury and fibrosis through activation of HSCs. PMID- 26264938 TI - Preconception risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease. AB - BACKGROUND: Globally, about five per cent of children are born with congenital or genetic disorders. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in specific patient populations. Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions, with some of these choices not being available if genetic counselling is only offered in an antenatal setting. OBJECTIVES: To assess the effectiveness of systematic preconception genetic risk assessment to improve reproductive outcomes in women and their partners who are identified as carriers of thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease in healthcare settings when compared to usual care. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Registers. In addition, we searched for all relevant trials from 1970 (or the date at which the database was first available if after 1970) to date using electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), clinical trial databases (National Institutes of Health, Clinical Trials Search portal of the World Health Organization, metaRegister of controlled clinical trials), and hand searching of key journals and conference abstract books from 1998 to date (European Journal of Human Genetics, Genetics in Medicine, Journal of Community Genetics). We also searched the reference lists of relevant articles, reviews and guidelines and also contacted subject experts in the field to request any unpublished or other published trials.Date of latest search of the registers: 25 June 2015.Date of latest search of all other sources: 10 December 2014. SELECTION CRITERIA: Any randomised or quasi-randomised control trials (published or unpublished) comparing reproductive outcomes of systematic preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay Sachs disease when compared to usual care. DATA COLLECTION AND ANALYSIS: We identified 19 papers, describing 13 unique trials which were potentially eligible for inclusion in the review. However, after assessment, no randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease were found. MAIN RESULTS: No randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease were found. AUTHORS' CONCLUSIONS: As no randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis, or Tay-Sachs disease were found for inclusion in this review, the research evidence for current policy recommendations is limited to non-randomised studies.Information from well-designed, adequately powered, randomised trials is desirable in order to make more robust recommendations for practice. However, such trials must also consider the legal, ethical, and cultural barriers to implementation of preconception genetic risk assessment. PMID- 26264937 TI - Quality of life and acquired organ damage are intimately related to activity limitations in patients with systemic lupus erythematosus. AB - BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune multi-organ disease, characterized by episodes of disease flares and remissions over time, which may restrain affected patients' ability to perform daily activities. The purpose of the present study was to characterize variation in activity limitations among well-defined SLE patients, and to describe disease phenotypes, acquired organ damage and their relations to activity limitation and self reported health, respectively. METHODS: The disease phenotypes were organized into 4 different clinical groups and logistic regression analyses were used to identify how an elevated health assessment questionnaire (HAQ) score was related to disease variables such as phenotypes, disease activity and damage accrual. Correlation and multiple linear regression analyses were used to examine the association between each group of variables - background variables, disease variables and self-reported measurements - and the degree of elevated HAQ. RESULTS: We found a higher proportion of activity limitation in patients with skin and joint involvement compared to others. The presence of activity limitation, as detected by the HAQ instrument, was significantly associated with quality of life (EuroQol-5D) and accrual of organ damage using the Systemic Lupus International Collaborative Clinics/ACR damage index. CONCLUSIONS: The findings highlight the differing requirements of the multi-professional rehabilitation interventions for the various SLE phenotypes in order to optimize the clinical care of the patients. PMID- 26264939 TI - Site-Selective Conjugate Addition Through Catalytic Generation of Ion-Pairing Intermediates. AB - Site-selectivity in conjugate addition reactions is tightly associated with the principle of vinylogy. Various vinylogous nucleophiles and electrophiles have been applied to stereoselective conjugate additions directed by chiral small molecule catalysts. This chapter focuses on the systems that control site- and stereoselectivity via chiral ion-pairing intermediates under organocatalytic conditions and describes individual vinylogous substrates in a separate section. Although site-selectivity originates largely from the intrinsic stereoelectronic nature of individual substrates, catalyst-controlled site-selectivity can be attained in certain cases. PMID- 26264940 TI - Insights into IL-37, the role in autoimmune diseases. AB - Autoimmune diseases are characterized by the impaired function and the destruction of tissues that are caused by an immune response in which aberrant antibodies are generated and attack the body's own cells and tissues. Interleukin (IL) -37, a new member of the IL-1 family, broadly reduces innate inflammation as well as acquired immune responses. Recently, studies have shown that expression of IL-37 was abnormal in autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), ankylosing spondylitis (AS), psoriasis, Graves' disease (GD). In addition, functional analysis indicated that IL-37 is negatively involved in the development and pathogenesis of these autoimmune disorders. The strong association of this cytokine with autoimmune diseases promotes us to systematically review what had been published recently on the crucial nature of IL-37 in relation to autoimmune diseases gaining attention for its regulatory capability in these autoimmune disorders. PMID- 26264941 TI - Thrombolysis for stroke in pregnancy at 39 weeks gestation with a subsequent normal delivery. AB - Stroke during pregnancy is fortunately a rare event, however, it can have severe consequences, with 9.5% of all maternal deaths being related to stroke. The most common presentation is an ischaemic stroke. There has been much debate as to the correct treatment for such cases' and whether thrombolysis can be used safely in pregnancy. Our case describes a 28-year-old woman with a previous normal vaginal delivery presenting in her third trimester with a sudden onset of dense left hemiparesis. She was successfully treated with alteplase, an intravenous recombinant tissue-type plasminogen activator, and made a full recovery after normal delivery of a healthy infant. This case report highlights one of the first documented successful outcomes from thrombolysis for this condition in the UK and may help inform future management of these women. PMID- 26264942 TI - Toxic shock syndrome post open reduction and Kirschner wire fixation of a humeral lateral condyle fracture. AB - Use of Kirschner wires (K-wires) is the most common method of fracture stabilisation in lateral condyle fracture fixation in children. We report a case of toxic shock syndrome (TSS) following an open reduction and internal fixation using K-wires for a humeral lateral condyle fracture in a 5-year-old girl. TSS is a toxin-mediated multisystem illness. It typically presents with shock and it is most often attributed to toxin-producing strains of Staphylococcus aureus and Streptococcus pyogenes. It can lead to multiorgan failure and, ultimately, death. It is important to be aware of TSS, as it can present within any setting. Patients often have non-specific symptoms and their condition can worsen rapidly. TSS postorthopaedic surgery is rare; however, due to the serious nature of this disease, it is important to promptly recognise and diagnose TSS, and to ensure appropriate treatment is started without delay. PMID- 26264943 TI - Myositis ossificans of the quadriceps femoris in a soccer player. AB - A young soccer player was diagnosed with myositis ossificans 6 weeks after a muscle strain in the right thigh. Radiographic and sonographic investigations initially helped to confirm diagnosis and later supported clinical improvement. We present our approach to the case and discuss pathophysiology, prevention and treatment of this rare condition. PMID- 26264944 TI - Streptococcus gordonii prosthetic joint infection in the setting of vigorous dental flossing. AB - A 65-year-old woman with osteoarthritis, who underwent knee replacement 5 years prior, developed sudden onset knee pain and swelling. She had voluntarily starting a vigorous dental flossing regimen prior to the onset of symptoms. The patient underwent right knee arthrotomy, irrigation and debridement of right total knee arthroplasty and exchange of polyethylene with retention of the prosthesis. Intraoperative cultures grew Streptococcus gordonii. She was treated with 6 weeks of ceftriaxone and was later placed on oral antibiotic suppression. PMID- 26264945 TI - Use of steroids for management of varicella pneumonia. AB - Varicella pneumonia (VP) is a critical complication of varicella infection and still carries significant morbidity and mortality, often requiring intensive care unit admission. Current accepted treatment is with intravenous aciclovir and organ support, if required. We report two cases of VP with acute respiratory failure, successfully treated with intravenous steroids in addition to aciclovir. Further research into the benefits of steroid therapy in VP is warranted. PMID- 26264946 TI - Obstructive eosinophilic gastroenteritis in a patient with rheumatoid arthritis. AB - Eosinophilic gastroenteritis (EG) is a rare disease characterised by abnormal eosinophilic infiltration of the gastrointestinal tract. We describe a case of EG presenting as an intestinal obstruction in a patient with rheumatoid arthritis (RA). A 54-year-old man with RA presented to the emergency department with abdominal pain and vomiting. On examination, his abdomen was distended and tender. Laboratory data showed leucocytosis with raised inflammatory markers and without eosinophilia. CT revealed dilated small bowel loops, with a couple of loops forming a mass and abscess formation. Emergency laparotomy was performed with segmental resection of the ileum and side-to-side anastomosis. Histology confirmed the diagnosis of EG. The patient recovered well and was asymptomatic at the time of writing this report. PMID- 26264948 TI - Transient renal medullary hyperechogenicity in a term neonate. AB - Although neonatal renal medullary hyperechogenicity can occur in a variety of pathological conditions, it has been reported to occur transiently with or without renal abnormalities in term as well as in preterm neonates. Variably described in the literature as Tamm-Horsfall nephropathy, or stasis nephropathy, the pathogenesis is unknown, but has an excellent prognosis. The authors describe a 3-day-old neonate with transient renal medullary hyperechogenicity, with no other abnormalities, which resolved within 2 weeks. PMID- 26264947 TI - Treatment for tuberculosis in a patient with Dubin-Johnson syndrome. AB - Dubin-Johnson syndrome (DJS) is an autosomal recessive disorder characterised by conjugated hyperbilirubinemia resulting from mutations of ABCC2/MRP2 gene. The beneficial effects of ursodeoxycholic acid (UDCA) and rifampicin were found to be complementary in the treatment of cholestatic liver disease secondary to DJS. We present a case of a young woman with tubercular meningitis. She was started on modified antitubercular therapy in view of conjugated hyperbilirubinemia. However, reinitiation of rifampicin resulted in redevelopment of jaundice. Liver biopsy was suggestive of DJS. The patient was started on rifampicin along with UDCA. There was improvement in hyperbilirubinemia and a full course of antituberculous therapy without further worsening of the disorder was possible. This is a rare case of DJS with tuberculosis, showing beneficial effects of rifampicin and UDCA combination therapy, which so far has been considered doubtful. It is uncertain what the level of efficacy of therapy is in various MRP2 gene mutations. PMID- 26264949 TI - Isolated hydatid cyst of the pancreas masquerading as pancreatic pseudocyst. AB - Hydatid cyst of the pancreas is very rare and usually presents with obstructive jaundice. We report a case of a 7-year-old girl with cyst of the pancreas without any obstructive jaundice. The child was treated surgically and hydatid cyst of pancreas was found. Partial pericystectomy was performed. After 1 month on follow up, the child developed pseudocyst of pancreas, which needed cystogastrostomy. Postoperatively, the child improved and is remaining well after 3 months of follow-up. Hydatid cysts of pancreas are very difficult to diagnose preoperatively and should be kept as a differential diagnosis of cystic intrapancreatic lesions. Serological tests can help in early diagnosis. PMID- 26264950 TI - Orbital metastasis from prostate cancer. PMID- 26264951 TI - Non-union of the great toe in a 4-year-old child. AB - Phalangeal fractures of the foot are very rare in children. They are treated with closed reduction and splinting. Cases reported of non-union in children are rare. We report on treatment of a 4-year-old child with non-union of the proximal phalanx of the great toe foot following an open fracture caused by a motor vehicle accident 4 months prior. No graft was used. We present this case with good clinical outcome at 1 year follow-up. PMID- 26264952 TI - An unusual cause of proptosis. PMID- 26264953 TI - XDR TB presenting as a transphyseal lytic lesion in the proximal tibia. PMID- 26264954 TI - A morphometric 3D model of coronary artery bypass graft dysfunction with multidetector computed tomography. AB - OBJECTIVE: The objective was to assess, with computed tomography (CT) angiography, quantitative morphological parameters of a composite coronary artery bypass grafting (CABG) strategy and to correlate these with graft dysfunction. FINDINGS: Forty patients [median postoperative time, 32 (14-51) months] underwent CT angiography. Graft patency was assessed, and specific quantitative morphological parameters of the graft were collected. Graft segments had an overall patency rate of 93% (78/84). Two specific morphological parameters were found to be associated with graft dysfunction. CONCLUSION: A CT morphometric model can be used to identify quantitative 3D parameters associated with graft dysfunction. Such an approach could help in developing and improving CABG designs. PMID- 26264955 TI - Elevated Z line: a new sign of Barrett's esophagus on double-contrast barium esophagograms. AB - We describe an elevated Z line as a new radiographic sign of Barrett's esophagus characterized by a transversely oriented, zigzagging, barium-etched line extending completely across the circumference of the midesophagus. An elevated Z line is rarely seen in other patients, so this finding should be highly suggestive of Barrett's esophagus on double-contrast barium esophagograms. If the patient is a potential candidate for surveillance, endoscopy and biopsy should be performed to confirm the presence of Barrett's esophagus. PMID- 26264956 TI - Can computed tomography esophagography reliably diagnose traumatic penetrating upper digestive tract injuries? AB - OBJECTIVE: To determine the sensitivity and specificity of computed tomography (CT) esophagography in diagnosing penetrating esophageal and hypopharyngeal injuries in trauma patients and to see if it can be used as the only imaging method in diagnosing these injuries. The confidence of radiologists using only CT esophagography was also measured. PATIENTS AND METHODS: A prospective cross sectional analytic study was done on haemodinamically stable patients requiring multidetector CT after external penetrating neck or chest trauma. Each patient was given oral contrast consisting of 50 ml 50% iohexol solution, within 5 min of commencement of the CT examination and in the supine position. An attempt was made to confirm all CT esophagography findings with at least one secondary method. Images were evaluated separately by two general departmental radiologists who were blinded to the results of the confirmation method. RESULTS: Between December 2012 and November 2014, 102 patients were included, of which 93 (91.2%) were male. Stab wounds were responsible for 85.3% (n=87) of penetrating wounds. Ninety-four patients (92.2%) had CT angiography (CTA) in conjunction with CT esophagography. There were 20 confirmed upper digestive tract injuries; 11 (55.0%) in the hypopharynx and 9 (45.0%) in the esophagus. With the exception of one case, all upper digestive tract injuries were diagnosed using only CT esophagography. No upper digestive tract injuries were correctly identified in 70 and 75 out of 82 true negative cases respectively, suggesting a sensitivity of 95.0% for both radiologists and specificity of 85.4% and 91.5% for CT esophagography. A number of false positive diagnoses were reported when CT esophagography was done in conjunction with CTA, resulting in a positive predictive value of 61.3% and 79.1% for this technique. Reviewers were positive to very confident about the CT esophagography findings in 90.0% and 100% of patients with injuries and 79.0% and 87.0%, respectively, in the no injury group. CONCLUSION: CT esophagography is reliable in diagnosing penetrating upper digestive tract injuries. In conjunction with CTA, false positive findings may occur. Radiologists were generally positive to very confident about their CT esophagography findings, not needing further imaging in more than 60% of cases. PMID- 26264957 TI - Diagnostic accuracy of reused Pronto Drytest and CLOtest in the detection of Helicobacter pylori infection. AB - BACKGROUND: Unchanged substrate in a negative rapid urease test may be reused to detect Helicobacter pylori (H. pylori). This could potentially reduce costs and wastage in low prevalence and resource-poor settings. We thus aimed to investigate the diagnostic accuracy of reused Pronto Dry and CLOtest kits, comparing this to the use of new Pronto Dry test kits and histopathological evaluation of gastric mucosal biopsies. METHODS: Using a cross-sectional study design, subjects who presented for upper endoscopy due to various non-emergent causes had gastric biopsies obtained at three adjacent sites. Biopsy samples were tested for H. pylori using a reused Pronto Dry test, a reused CLOtest, a new Pronto Dry test and histopathological examination. Concordance rates, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy were then determined. RESULTS: A total of 410 subjects were recruited. The sensitivity and diagnostic accuracy of reused Pronto Dry tests were 72.60 % (95% CI, 61.44 - 81.51) and 94.15% (95% CI, 91.44 - 96.04) respectively. For reused CLOtests, the sensitivity and diagnostic accuracy were 93.15% (95% CI 85.95 - 97.04) and 98.29% (95% CI 96.52 - 99.17) respectively. There were more true positives for new and reused Pronto Dry pallets as compared to new and reused CLOtests when comparing colour change within 30 min vs. 31-60 min (P < 0.001 and P = 0.7 respectively). CONCLUSION: Negative Pronto Dry and CLOtest kits may be reused in a low prevalence setting where cost issues remain paramount. Reused CLOtest kits have better accuracy than reused Pronto Dry tests. Reused Pronto Dry tests however have a more rapid colour change whilst maintaining diagnostic accuracy. PMID- 26264958 TI - Metal Free Azide-Alkyne Click Reaction: Role of Substituents and Heavy Atom Tunneling. AB - Metal free click reactions provide an excellent noninvasive tool to modify and understand the processes in biological systems. Release of ring strain in cyclooctynes on reaction with azides on the formation of triazoles results in small activation energies for various intermolecular Huisgen reactions (1-9). Substitution of difluoro groups at the alpha, alpha' position of the cyclooctyne ring enhances the rates of cycloadditions by 10 and 20 times for methyl azide and benzyl azide respectively at room temperature. The computed rate enhancement on difluoro substitution using direct dynamical calculations using the canonical variational transition state theory (CVT/CAG) with small curvature tunneling (SCT) corrections are in excellent agreement with the experimental results. For the intramolecular click reaction (10) notwithstanding its much higher activation energy, quantum mechanical tunneling (QMT) enhances the rate of cycloaddition significantly and increases the N(14)/N(15) primary kinetic isotope effect at 298 K. QMT is shown to be rather efficient in 10 due to a thin barrier of ~2.4 A. The present study shows that tunneling effects can be significant for intramolecular click reactions. PMID- 26264959 TI - Y-chromosomal testing of brown bears (Ursus arctos): Validation of a multiplex PCR-approach for nine STRs suitable for fecal and hair samples. AB - High-resolution Y-chromosomal markers have been applied to humans and other primates to study population genetics, migration, social structures and reproduction. Y-linked markers allow the direct assessment of the genetic structure and gene flow of uniquely male inherited lineages and may also be useful for wildlife conservation and forensics, but have so far been available only for few wild species. Thus, we have developed two multiplex PCR reactions encompassing nine Y-STR markers identified from the brown bear (Ursus arctos) and tested them on hair, fecal and tissue samples. The multiplex PCR approach was optimized and analyzed for species specificity, sensitivity and stutter-peak ratios. The nine Y-STRs also showed specific STR-fragments for male black bears and male polar bears, while none of the nine markers produced any PCR products when using DNA from female bears or males from 12 other mammals. The multiplex PCR approach in two PCR reactions could be amplified with as low as 0.2 ng template input. Precision was high in DNA templates from hairs, fecal scats and tissues, with standard deviations less than 0.14 and median stutter ratios from 0.04 to 0.63. Among the eight di- and one tetra-nucleotide repeat markers, we detected simple repeat structures in seven of the nine markers with 9-25 repeat units. Allelic variation was found for eight of the nine Y-STRs, with 2-9 alleles for each marker and a total of 36 alleles among 453 male brown bears sampled mainly from Northern Europe. We conclude that the multiplex PCR approach with these nine Y-STRs would provide male bear Y-chromosomal specificity and evidence suited for samples from conservation and wildlife forensics. PMID- 26264960 TI - Genetic distribution of 39 STR loci in 1027 unrelated Han individuals from Northern China. PMID- 26264961 TI - Accurate chromosome segregation by probabilistic self-organisation. AB - BACKGROUND: For faithful chromosome segregation during cell division, correct attachments must be established between sister chromosomes and microtubules from opposite spindle poles through kinetochores (chromosome bi-orientation). Incorrect attachments of kinetochore microtubules (kMTs) lead to chromosome mis segregation and aneuploidy, which is often associated with developmental abnormalities such as Down syndrome and diseases including cancer. The interaction between kinetochores and microtubules is highly dynamic with frequent attachments and detachments. However, it remains unclear how chromosome bi orientation is achieved with such accuracy in such a dynamic process. RESULTS: To gain new insight into this essential process, we have developed a simple mathematical model of kinetochore-microtubule interactions during cell division in general, i.e. both mitosis and meiosis. Firstly, the model reveals that the balance between attachment and detachment probabilities of kMTs is crucial for correct chromosome bi-orientation. With the right balance, incorrect attachments are resolved spontaneously into correct bi-oriented conformations while an imbalance leads to persistent errors. In addition, the model explains why errors are more commonly found in the first meiotic division (meiosis I) than in mitosis and how a faulty conformation can evade the spindle assembly checkpoint, which may lead to a chromosome loss. CONCLUSIONS: The proposed model, despite its simplicity, helps us understand one of the primary causes of chromosomal instability-aberrant kinetochore-microtubule interactions. The model reveals that chromosome bi-orientation is a probabilistic self-organisation, rather than a sophisticated process of error detection and correction. PMID- 26264962 TI - How to develop a more accurate risk prediction model when there are few events. PMID- 26264963 TI - Higher freshwater fish and sea fish intake is inversely associated with colorectal cancer risk among Chinese population: a case-control study. AB - The association between specific fish intake and colorectal cancer risk remains controversial. This study aimed to examine the association between specific fish intake and colorectal cancer risk in Chinese population in a large case control study. During July 2010 to November 2014, 1189 eligible colorectal cancer cases and 1189 frequency-matched controls (age and sex) completed in-person interviews. A validated food frequency questionnaire was used to estimate dietary intake. Multivariate logistical regression models were used to estimate the odds ratio (OR) and 95% confidence interval (95% CI) after adjusting for various confounders. A strong inverse association was found between freshwater fish intake and colorectal cancer risk. Compared with the lowest quartile, the highest quartile intake showed a risk reduction of 53% (OR 0.47, 95% CI = 0.36-0.60, Ptrend < 0.01) after adjustment for various confounders. The inverse association were also observed for sea fish (OR 0.79, 95%CI = 0.62-0.99, Ptrend < 0.01) and fresh fish (OR 0.49, 95%CI = 0.38-0.62, Ptrend < 0.01). No statistically significant association was found between dried/salted fish and shellfish intake and colorectal cancer risk. These results indicate that higher consumption of freshwater fish, sea fish and fresh fish is associated with a lower risk of colorectal caner. PMID- 26264964 TI - Continuous neurodegeneration and death pathway activation in neurons and glia in an experimental model of severe chronic epilepsy. AB - Whether seizures might determine the activation of cell death pathways and what could be the relevance of seizure-induced cell death in epilepsy are still highly debated issues. We recently developed an experimental model of acquired focal cortical dysplasia (the MAM-pilocarpine or MP rat) in which the occurrence of status epilepticus--SE--and subsequent seizures induced progressive cellular/molecular abnormalities and neocortical/hippocampal atrophy. Here, we exploited the same model to verify when, where, and how cell death occurred in neurons and glia during epilepsy course. We analyzed Fluoro Jade (FJ) staining and the activation of c-Jun- and caspase-3-dependent pathways during epilepsy, from few hours post-SE up to six months of spontaneous recurrent seizures. FJ staining revealed that cell injury in MP rats was not temporally restricted to SE, but extended throughout the different epileptic stages. The region-specific pattern of FJ staining changed during epilepsy, and FJ(+) neurons became more prominent in the dorsal and ventral hippocampal CA at chronic epilepsy stages. Phospho-c-Jun- and caspase-3-dependent pathways were selectively activated respectively in neurons and glia, at early but even more conspicuously at late chronic stages. Phospho-c-Jun activation was associated with increased cytochrome c staining, particularly at chronic stages, and the staining pattern of cytochrome-c was suggestive of its release from the mitochondria. Taken together, these data support the content that at least in the MP rat model the recurrence of seizures can also sustain cell death mechanisms, thus continuously contributing to the pathologic process triggered by the occurrence of SE. PMID- 26264965 TI - VaCPK20, a calcium-dependent protein kinase gene of wild grapevine Vitis amurensis Rupr., mediates cold and drought stress tolerance. AB - Abiotic stresses, such as drought, salinity, cold and heat, are major environmental factors that limit crop productivity. Vitis amurensis Rupr. is a wild grapevine species displaying a high level of abiotic and biotic stress resistance. Protein kinases, including Ca(2+)-dependent protein kinases (CDPKs), are known to mediate plant acclimation to various environmental changes. However, the functions of most grape CDPKs have not been clarified. A recent CDPK gene expression analysis revealed that 10 CDPK genes of V. amurensis were up-regulated under different abiotic stress treatments. The expression of the VaCPK20 gene was significantly up-regulated under low and high temperature stress in V. amurensis. In the current study, the effects of overexpressing the VaCPK20 gene in callus cell lines of V. amurensis and transgenic plants of A. thaliana on their responses to abiotic stresses were investigated. Transgenic Arabidopsis overexpressing the VaCPK20 gene showed higher tolerance to freezing and drought stresses, and transgenic grape cell cultures overexpressing the VaCPK20 gene showed higher resistance to cold stress in comparison with the controls transformed by the "empty" vector. Heat and salt stress resistance of the transgenic V. amurensis calli and A. thaliana was comparable to that of the wild type and vector controls. Overexpression of the VaCPK20 gene increased the expression of stress-responsive genes, such as COR47, NHX1, KIN1, or ABF3, in the transgenic Arabidopsis plants under non-stress conditions, after freezing, and under drought stress. The results imply that VaCPK20 may act as a regulatory factor involved in cold and drought stress response pathways. PMID- 26264966 TI - A proteome map of a quadruple photoreceptor mutant sustains its severe photosynthetic deficient phenotype. AB - Light is the environmental factor that most affects plant growth and development through its impact on photomorphogenesis and photosynthesis. A quadruple photoreceptor mutant lacking four of the most important photoreceptors in plants, phytochromes A and B (phyA, phyB) and cryptochromes 1 and 2 (cry1, cry2), is severely affected in terms of growth and development. Previous studies have suggested that in addition to a photomorphogenic disorder, the phyA phyB cry1 cry2 quadruple mutant might have severe alterations in photosynthetic ability. Here, we investigated the photosynthetic processes altered in the quadruple mutant and performed a proteomic profiling approach to identify some of the proteins involved. The phyA phyB cry1 cry2 quadruple mutant showed reduced leaf area and total chlorophyll content. Photosynthetic rates at high irradiances were reduced approximately 65% compared to the wild type (WT). Light-saturated photosynthesis and the response of net CO2 exchange to low and high internal CO2 concentrations suggest that the levels or activity of the components of the Calvin cycle and electron transport might be reduced in the quadruple mutant. Most of the under-expressed proteins in the phyA phyB cry1 cry2 quadruple mutant consistently showed a chloroplastic localization, whereas components of the Calvin cycle and light reaction centers were overrepresented. Additionally, Rubisco expression was reduced threefold in the phyA phyB cry1 cry2 quadruple mutant. Together, these results highlight the importance of the phytochrome and cryptochrome families in proper autotrophy establishment in plants. They also suggest that an overall limitation in the chlorophyll levels, expression of Rubisco, and enzymes of the Calvin Cycle and electron transport that affect ribulose-1,5-biphosphate (RuBP) regeneration reduced photosynthetic capacity in the phyA phyB cry1 cry2 quadruple mutant. PMID- 26264967 TI - Recovery of tomato (Solanum lycopersicum L.) leaves from continuous light induced injury. AB - Continuous light (CL) causes leaf injuries in tomato plants, but very little has been done to study the nature of recovery from these leaf injuries. To facilitate this, tomato plants (Solanum lycopersicum L. cv. 'Aromata') were first exposed to CL for 11 days in order to study the development of the leaf injuries. Afterwards, the plants were exposed to a photoperiodic treatment with a dark period of eight hours to study the nature of recovery of the leaves. Plants were grown in two photoperiodic treatments in climate chambers; a control treatment with a 16/8h light/dark and a CL treatment with 24h light. The two treatments had different light intensities to maintain a similar daily light integral (15 mol m( 2)d(-1)). The temperature and humidity were adjusted to maintain a similar vapor pressure deficit (VPD) of 1kPa in the two treatments. After 11 days of CL, 12% of the total leaflet area appeared light green in spots on the leaf surface aligned with lower total leaf chlorophyll content. The light green spots partially reversed while the leaf chlorophyll content increased to similar levels as seen in control leaves after 11 days of recovery. The CL significantly reduced the stomatal conductance (gs) and net photosynthesis (PN) and altered the carbohydrate content in the leaves. These negative effects of CL were also rapidly restored to the control levels when the plants were returned to the 16h photoperiodic conditions. The results demonstrate that, though leaf discoloration is only partially recovered, tomato plants can be grown for 11 days in CL conditions with the development of chlorotic discoloration of the leaves covering 12% of the leaf surface and rapidly recover physiological processes affected by CL by shortening the photoperiod to 16h. PMID- 26264968 TI - The context, influences and challenges for undergraduate nurse clinical education: Continuing the dialogue. AB - INTRODUCTION: Approaches to clinical education are highly diverse and becoming increasingly complex to sustain in complex milieu OBJECTIVE: To identify the influences and challenges of providing nurse clinical education in the undergraduate setting and to illustrate emerging solutions. METHOD: A discursive exploration into the broad and varied body of evidence including peer reviewed and grey literature. DISCUSSION: Internationally, enabling undergraduate clinical learning opportunities faces a range of challenges. These can be illustrated under two broad themes: (1) legacies from the past and the inherent features of nurse education and (2) challenges of the present, including, population changes, workforce changes, and the disconnection between the health and education sectors. Responses to these challenges are triggering the emergence of novel approaches, such as collaborative models. CONCLUSION(S): Ongoing challenges in providing accessible, effective and quality clinical learning experiences are apparent. PMID- 26264969 TI - Downregulation of key regulatory proteins in androgen dependent prostate tumor cells by oncolytic reovirus. AB - As prostate tumor cell growth depends on hormones, androgen ablation is an effective therapy for prostate cancer (PCa). However, progression of PCa cells to androgen independent growth (castrate resistant prostate cancer, CRPC) results in relapse and mortality. Hypoxia, a microenvironment of low oxygen that modifies the activity of PCa regulatory proteins including the androgen receptor (AR), plays a critical role in progression to CRPC. Therapies targeting hypoxia and the AR may lengthen the time to CRPC progression thereby increasing survival time of PCa patients. Mammalian Orthoreovirus (MRV) has shown promise for the treatment of prostate tumors in vitro and in vivo. In this study, we found that MRV infection induces downregulation of proteins implicated in CRPC progression, interferes with hypoxia-induced AR activity, and induces apoptosis in androgen dependent cells. This suggests MRV possesses traits that could be exploited to create novel therapies for the inhibition of progression to CRPC. PMID- 26264970 TI - Characterization of Frog Virus 3 knockout mutants lacking putative virulence genes. AB - To identify ranavirus virulence genes, we engineered Frog Virus 3 (FV3) knockout (KO) mutants defective for a putative viral caspase activation and recruitment domain-containing (CARD) protein (Delta64R-FV3) and a beta-hydroxysteroid dehydrogenase homolog (Delta52L-FV3). Compared to wild type (WT) FV3, infection of Xenopus tadpoles with Delta64R- or Delta52L-FV3 resulted in significantly lower levels of mortality and viral replication. We further characterized these and two earlier KO mutants lacking the immediate-early18kDa protein (FV3 Delta18K) or the truncated viral homolog of eIF-2alpha (FV3-DeltavIF-2alpha). All KO mutants replicated as well as WT-FV3 in non-amphibian cell lines, whereas in Xenopus A6 kidney cells replication of DeltavCARD-, DeltavbetaHSD- and DeltavIF 2alpha-FV3 was markedly reduced. Furthermore, Delta64R- and DeltavIF-2alpha-FV3 were more sensitive to interferon than WT and Delta18-FV3. Notably, Delta64R-, Delta18K- and DeltavIF-2alpha- but not Delta52L-FV3 triggered more apoptosis than WT FV3. These data suggest that vCARD (64R) and vbeta-HSD (52L) genes contribute to viral pathogenesis. PMID- 26264972 TI - An in silico approach towards the identification of novel inhibitors of the TLR-4 signaling pathway. AB - Precise functioning and fine-tuning of Toll-like receptor 4 (TLR4) signaling is a critical requirement for the smooth functioning of the innate immune system, since aberrant TLR4 activation causes excessive production of pro-inflammatory cytokines and interferons. This can result in life threatening conditions such as septic shock and other inflammatory disorders. The TRIF-related adaptor molecule (TRAM) adaptor protein is unique to the TLR4 signaling pathway and abrogation of TRAM-mediated TLR4 signaling is a promising strategy for developing therapeutics aimed at disrupting TRAM interactions with other components of the TLR4 signaling complex. The VIPER motif from the vaccinia virus-producing protein, A46 has been reported to disrupt TRAM-TLR4 interactions. We have exploited this information, in combination with homology modeling and docking approaches, to identify a potential binding site on TRAM lined by the BB loop and alphaC helix. Virtual screening of commercially available small molecules targeting the binding site enabled to short-list 12 small molecules to abrogate TRAM-mediated TLR4 signaling. Molecular dynamics and molecular mechanics calculations have been performed for the analysis of these receptor-ligand interactions. PMID- 26264971 TI - Changes in the biochemical and immunological components of serum and colostrum of overweight and obese mothers. AB - BACKGROUND: Obesity in pregnancy is associated with systemic inflammation, immunological changes and adverse maternal-fetal outcomes. Information on the association between maternal obesity and breast milk composition is scarce. This study describes changes and relationships between biochemical and immunological parameters of colostrum and serum of overweight and obese women. METHODS: Colostrum and blood samples were collected from 25 normal weight, 24 overweight and 19 obese women for determination of glucose, total protein, triglycerides, cholesterol, immunoglobulins, complement proteins (C3 and C4), fat and calorie content and C-reactive protein (CRP). RESULTS: Glucose was higher in colostrum of obese women (p = .002). In normal weight and obese women, total protein content was higher in colostrum than in serum (p = .001). Serum triglycerides (p = .008) and cholesterol (p = .010) concentrations were significantly higher in overweight and obese women than in their normal weight counterparts, but in colostrum their concentrations were similar across the three groups. Secretory IgA (sIgA) in colostrum and IgA in serum concentrations were significantly higher (p = .001) in overweight and obese mothers, whereas IgG and IgM concentrations did not vary among the groups (p = .825). Serum C3 (p = .001) and C4 (p = .040) concentrations were higher in obese women. No differences in colostrum complement proteins were detected among the groups. Calorie content (p = .003) and fat (p = .005) concentrations in colostrum and serum CRP (p = .002) were higher in obese women. CONCLUSIONS: The results corroborate the hypothesis that colostrum of overweight and obese women undergoes biochemical and immunological changes that affect its composition, namely increasing glucose concentrations, calorie content, fat and sIgA concentrations. PMID- 26264973 TI - Dipeptide recognition in water mediated by mixed monolayer protected gold nanoparticles. AB - Mixed monolayer protected gold nanoparticles were prepared featuring functional groups on their surfaces that can engage in interactions with peptides. DOSY NMR binding studies indicate that nanoparticles containing a combination of three orthogonal functional groups are more efficient in binding to dipeptides than mono or difunctionalised analogues. PMID- 26264974 TI - Appearance of annular ring-like intermediates during amyloid fibril formation from human serum albumin. AB - The self-assembly of proteins triggered by a conformational switch into highly ordered beta-sheet rich amyloid fibrils has captivated burgeoning interest in recent years due to the involvement of amyloids in a variety of human diseases and a diverse range of biological functions. Here, we have investigated the mechanism of fibrillogenesis of human serum albumin (HSA), an all-alpha-helical protein, using an array of biophysical tools that include steady-state as well as time-resolved fluorescence, circular dichroism and Raman spectroscopy in conjunction with atomic force microscopy (AFM). Investigations into the temporal evolution of nanoscale morphology using AFM revealed the presence of ring-like intermediates that subsequently transformed into worm-like fibrils presumably by a ring-opening mechanism. Additionally, a multitude of morphologically-diverse oligomers were observed on the pathway to amyloid formation. Kinetic analysis using multiple structural probes in-tandem indicated that HSA amyloid assembly is a concerted process encompassing a major structural change that is primarily mediated by hydrophobic interactions between thermally-induced disordered segments originating in various domains. A slower growth kinetics of aggregates suggested that the protein structural reorganization is a prerequisite for fibril formation. Moreover, time-dependent Raman spectroscopic studies of HSA aggregation provided key molecular insights into the conformational transitions occurring within the protein amide backbone and at the residue-specific level. Our data revealed the emergence of conformationally-diverse disulfides as a consequence of structural reorganization and sequestration of tyrosines into the hydrophobic amyloid core comprising antiparallel cross beta-sheets. PMID- 26264975 TI - Extensive Loss of Islet Mass Beyond the First Day After Intraportal Human Islet Transplantation in a Mouse Model. AB - Clinical islet transplantation is characterized by a progressive deterioration of islet graft function, which renders many patients once again dependent on exogenous insulin administration within a couple of years. In this study, we aimed to investigate possible engraftment factors limiting the survival and viability of experimentally transplanted human islets beyond the first day after their transplantation to the liver. Human islets were transplanted into the liver of nude mice and characterized 1 or 30 days after transplantation by immunohistochemistry. The factors assessed were endocrine mass, cellular death, hypoxia, vascular density and amyloid formation in the transplanted islets. One day posttransplantation, necrotic cells, as well as apoptotic cells, were commonly observed. In contrast to necrotic death, apoptosis rates remained high 1 month posttransplantation, and the total islet mass was reduced by more than 50% between 1 and 30 days posttransplantation. Islet mass at 30 days posttransplantation correlated negatively to apoptotic death. Vascular density within the transplanted islets remained less than 30% of that in native human islets up to 30 days posttransplantation and was associated with prevailing hypoxia. Amyloid formation was rarely observed in the 1-day-old transplants, but was commonly observed in the 30-day-old islet transplants. We conclude that substantial islet cell death occurs beyond the immediate posttransplantation phase, particularly through apoptotic events. Concomitant low vascularization with prevailing hypoxia and progressive amyloid development was observed in the human islet grafts. Strategies to improve engraftment at the intraportal site or change of implantation site in the clinical setting are needed. PMID- 26264976 TI - Corrigendum: Genome-wide adaptive complexes to underground stresses in blind mole rats Spalax. PMID- 26264977 TI - [Nursing and clinical safety. What is the way?]. PMID- 26264980 TI - Teneligliptin improves metabolic abnormalities in a mouse model of postmenopausal obesity. AB - A decrease in serum estrogen levels in menopause is closely associated with the development of visceral obesity and the onset of type 2 diabetes in women. In the present study, we demonstrated the therapeutic effects of the novel DPP4 inhibitor, teneligliptin, on the features of postmenopausal obesity in mice. In the control group, female C57BL/6 mice were sham-operated and maintained on a standard diet. In the postmenopausal obese group, ovariectomized (OVX) mice were maintained on a high-fat diet, and were referred to as OVX-HF. In the treated group, teneligliptin at 60 mg/kg per day was administrated to OVX-HF, and were referred to as Tene. After a 12-week food challenge, the metabolic phenotypes of these mice were analyzed. Body weight, fat accumulation, and glucose intolerance were greater in OVX-HF than in control, while these abnormalities were markedly improved without alterations in calorie intake in Tene. Teneligliptin effectively ameliorated the characteristics of metabolic abnormalities associated with postmenopausal obesity. Regarding chronic inflammation in visceral adipose tissue, the numbers of F4/80(+)CD11c(+)CD206(-) M1-macrophages in flow cytometry, crown-like structure formation in immunohistochemistry, and proinflammatory cytokine expression were significantly attenuated in Tene. Hepatic steatosis was also markedly improved. Furthermore, decreased energy consumption in the dark and light phases, reduced locomotor activity in the dark phase, and lowered core body temperature in OVX-HF were ameliorated in Tene. Since obesity and reduced energy metabolism are a common physiology of menopause, teneligliptin appears to be beneficial as a treatment for type 2 diabetes in postmenopausal obesity. PMID- 26264981 TI - Aging-related premature luteinization of granulosa cells is avoided by early oocyte retrieval. AB - Why IVF pregnancy rates decline sharply after age 43 is unknown. In this study, we compared granulosa cell (GC) function in young oocyte donors (n=31, ages 21 29), middle-aged (n=64, ages 30-37) and older infertile patients (n=41, ages 43 47). Gene expressions related to gonadotropin activity, steroidogenesis, apoptosis and luteinization were examined by real-time PCR and western blot in GCs collected from follicular fluid. FSH receptor (FSHR), aromatase (CYP19A1) and 17beta-hydroxysteroid dehydrogenase (HSD17B) expression were found down regulated with advancing age, while LH receptor (LHCGR), P450scc (CYP11A1) and progesterone receptor (PGR) were up regulated. Upon in vitro culture, GCs were found to exhibit lower proliferation and increased apoptosis with aging. While FSH supplementation stimulated GCs growth and prevented luteinization in vitro. These observations demonstrate age-related functional declines in GCs, consistent with premature luteinization. To avoid premature luteinization in women above age 43, we advanced oocyte retrieval by administering human chorionic gonadotropin at maximal leading follicle size of 16 mm (routine 19-21 mm). Compared to normal cycles in women of similar age, earlier retrieved patients demonstrated only a marginal increase in oocyte prematurity, yet exhibited improved embryo numbers as well as quality and respectable clinical pregnancy rates. Premature follicular luteinization appears to contribute to rapidly declining IVF pregnancy chances after age 43, and can be avoided by earlier oocyte retrieval. PMID- 26264983 TI - Differentiating confluent and reticulated papillomatosis from acanthosis nigricans. AB - BACKGROUND: Confluent and reticulated papillomatosis (CRP) is an uncommon dermatosis with a reticular pattern. As differentiation between CRP and benign acanthosis nigricans (AN) can be challenging because of their similar clinicopathological features, we aimed to distinguish the two diseases. METHODS: We retrospectively reviewed the clinical characteristics of 60 CRP and 30 AN patients. Histological examinations were conducted on 33 CRP and 30 AN lesions. RESULTS: While CRP was concentrated on the trunk, AN mostly appeared in the axilla. In the AN group, the number of obese patients was higher, and acanthosis and papillomatosis were more evident. In both group, increases in Ki-67 and keratin 16 expression were similar. Bacterial infection was detected at a higher rate in CRP lesions than in AN lesions.AN lesions had greater pigmentation because of a high number of melanocytes than CRP lesions. CONCLUSIONS: The location of skin lesions and body mass index are the main clinical factors that enable differentiation between CRP and AN. The epidermal histological changes in CRP are milder than those in AN. AN lesions also showed a greater degree of pigmentation and melanocytic proliferation. PMID- 26264982 TI - Clinical islet isolation and transplantation outcomes with deceased cardiac death donors are similar to neurological determination of death donors. AB - In islet transplantation, deceased cardiac death (DCD) donation has been identified as a potential extended source. There are currently no studies comparing outcomes between these categories, and our goal was to compare islet isolation success rates and transplantation outcomes between DCD and neurological determination of death (NDD) donors. Islet isolations from 15 DCD and 418 NDD were performed in our centre between September 2008 and September 2014. Donor variables, islet yields, metabolic function of isolated isled and insulin requirements at 1-month post-transplant were compared. Compared to NDD, pancreata from DCD were more often procured locally and donors required less vasopressive support (P < 0.001 and P = 0.023, respectively), but the other variables were similar between groups. Pre- and postpurification islet yields were similar between NDD and DCD (576 vs. 608 * 10(3) islet equivalent, P = 0.628 and 386 vs. 379, P = 0.881, respectively). The metabolic function was similar between NDD and DCD, as well as the mean decrease in insulin requirement at 1-month post transplantation (NDD: 64.82%; DCD: 60.17% reduction, P = 0.517). These results support the broader use of DCD pancreata for islet isolation. A much larger DCD islet experience will be required to truly determine noninferiority of both short and long-term outcomes. PMID- 26264986 TI - Unsymmetrical 1,1-diborated multisubstituted sp(3)-carbons formed via a metal free concerted-asynchronous mechanism. AB - We have experimentally proved the unsymmetrical 1,1-diboration of diazo compounds, formed in situ from aldehydes and cyclic and non-cyclic ketones, in the absence of any transition metal complex. The heterolytic cleavage of the mixed diboron reagent, Bpin-Bdan, and the formation of two geminal C-Bpin and C Bdan bonds has been rationalised based on DFT calculations to occur via a concerted-asynchronous mechanism. Diastereoselection is attained on substituted cyclohexanones and DFT studies provide understanding on the origin of the selectivity. The alkoxide-assisted selective deborylation of Bpin from multisubstituted sp(3)-carbon and generation of a Bdan stabilized carbanion, easily conducts a selective protodeboronation sequence. PMID- 26264985 TI - Retrospective benzene exposure assessment for a multi-center case-cohort study of benzene-exposed workers in China. AB - Quality of exposure assessment has been shown to be related to the ability to detect risk of lymphohematopoietic disorders in epidemiological investigations of benzene, especially at low levels of exposure. We set out to build a statistical model for reconstructing exposure levels for 2898 subjects from 501 factories that were part of a nested case-cohort study within the NCI-CAPM cohort of more than 110,000 workers. We used a hierarchical model to allow for clustering of measurements by factory, workshop, job, and date. To calibrate the model we used historical routine monitoring data. Measurements below the limit of detection were accommodated by constructing a censored data likelihood. Potential non linear and industry-specific time-trends and predictor effects were incorporated using regression splines and random effects. A partial validation of predicted exposures in 2004/2005 was performed through comparison with full-shift measurements from an exposure survey in facilities that were still open. Median cumulative exposure to benzene at age 50 for subjects that ever held an exposed job (n=1175) was 509 mg/m(3) years. Direct comparison of model estimates with measured full-shift personal exposure in the 2004/2005 survey showed moderate correlation and a potential downward bias at low (<1 mg/m(3)) exposure estimates. The modeling framework enabled us to deal with the data complexities generally found in studies using historical exposure data in a comprehensive way and we therefore expect to be able to investigate effects at relatively low exposure levels. PMID- 26264987 TI - From Overlooked to Looking Over: Lesbians in Children's and Young Adult Literature. AB - This introduction focuses on the relative absence of lesbians in scholarly and intellectual conversations about homosexuality in children's and young adult literature. It also discusses the various articles in this special issue of the Journal of Lesbian Studies. PMID- 26264988 TI - Representations in Award-Winning LGBTQ Young Adult Literature from 2000-2013. AB - Lesbian, gay, bisexual, transgendered, and queer (LGBTQ) young adult (YA) literature is increasing in popularity, with novels like Bil Wright's Putting Makeup on the Fat Boy winning the two LGBTQ YA honors--the Lambda Literary and Stonewall Book Awards--as well awards commending their cultural diversity. Despite the upsurge of celebrated LGBTQ YA literature, a study of the protagonists in Lambda- and Stonewall-winning YA novels from 2000-2013 reveals three findings: the dominance of White, gay, male characters contradicts the trend toward strong female protagonists in mainstream YA; stories about lesbians are primarily tragic; and there are no bisexual protagonists. PMID- 26264989 TI - If I Could Be Mine: Personal Power in Sara Farizan's If You Could Be Mine. AB - This article examines Sarah Farizan's young adult novel If You Could Be Mine. It concludes that the author evokes transnational and transgender issues as secondary story lines, while the novel's primary concern is with female personal power in an age of unprecedented opportunities for young lesbian women. Through the character of Sahar, the author models a way forward wherein women can insist on freely given love in the absence of the male body. Through Farizan's illustration of the progression of Sahar's and Nasrin's relationship, the author re-contextualizes what it means to fulfill lesbian desire. PMID- 26264990 TI - Rapunzel Loves Merida: Melodramatic Expressions of Lesbian Girlhood and Teen Romance in Tangled, Brave, and Femslash. AB - This article explores the melodramatic expression of lesbian girlhood and teen romance in Disney's Tangled (2010) and Disney Pixar's Brave (2012), as well as "Meripunzel" femslash, fan-authored romantic pairings of the animations' female protagonists. First, Anne Sexton's poem, "Rapunzel," offers a literary precedent for exploring lesbian themes in the fairy tale. The next section shows how Tangled and Brave invoke the narrative conventions of the family melodrama. This generic association reveals the films' uses of rhetoric familiar to youth coming out narratives, as well as other visual and aural coding suggestive of queer styles. The last section shows how Meripunzel femslash taps into the films' existing melodramatic narrative forms and visual aesthetics, rehearsing their coming-out rhetoric while addressing the pleasures of and problems facing lesbian teen romance. I conclude by problematizing the often conventional expressions of lesbian girlhood in femslash, ultimately arguing for their empowering potential, especially as they indicate revised definitions of "princess." PMID- 26264991 TI - The Best Lesbian Show Ever!: The Contemporary Evolution of Teen Coming-Out Narratives. AB - This article examines developing trends within adolescent lesbian coming-out narratives in contemporary literary fiction and television shows. I argue that these texts, including ABC Family's Pretty Little Liars (2010-present), Madeleine George's The Difference Between You and Me (2012), A.S. King's Ask the Passengers (2012), and MTV's Faking It (2014-present), all experiment with the coming-out process in ways that complicate traditional narratives of adolescent queerness. By positioning their respective queer protagonists within broader queer and allied communities, these works articulate new complexities facing the young lesbian and her developing sexuality. PMID- 26264992 TI - An Interview with Leslea Newman: A Punchy New Heather, Dolly Parton, and Orange is the New Black. AB - This interview with Leslea Newman took place on Monday, September 22, 2014. Newman, while quite prolific, is probably best known for her children's picture book, Heather Has Two Mommies, initially published in 1989. Heather became the cultural touchstone in discussions of not only lesbianism and children's literature, but book challenges and censorship, as well. In this interview, Newman speaks about the evolution of Heather and her various editions, new frontiers in both children's literature and representations of lesbians, identity politics and authorship, transgender issues and children's literature, and the continued need for diversity in literature for young readers. PMID- 26264993 TI - Reconceptualizing the Archetypal Trickster in Audre Lorde's Zami: A New Spelling of My Name. AB - Carl Jung categorizes the trickster as a psychological archetype and sets certain parameters for it. This article examines Audre Lorde's trickster Afrekete in Zami: A New Spelling of My Name (1982) and poses the question of how typically archetypal a Black, female, lesbian trickster can be. Lorde occupies an idiosyncratic position in the canon in terms of race, gender, and sexual orientation. She bestows new qualities on her trickster coming from the peripheries she dwells in and challenges the Jungian model. Through Afrekete's linguistic dexterity and sexual identity, Lorde transforms the trickster from being seemingly innocuous into a figure of resistance grounded in lesbian erotica. PMID- 26264995 TI - Olfaction in chemotherapy for head and neck malignancies. AB - OBJECTIVE: Systemic chemotherapy for different malignancies occurs alongside various side effects, including reduced sensory function. To date, little is known about the effect of chemotherapeutic agents on olfaction. The aim of this study was to provide new data about changes in sense of smell during chemotherapy among patients with advanced squamous cell carcinomas of the head and neck region. METHODS: In a prospective, controlled cohort study of patients undergoing up to three courses of chemotherapy (cis- or carboplatin, 5-fluorouracil and docetaxel), olfaction was evaluated prior to and directly following completing a cycle, as well as 3 weeks later with the beginning of the next cycle. For evaluation of sense of smell, the established Sniffin' Sticks test with a determination of threshold, discrimination and identification (TDI) was used. Thirty-three patients (44-85 years old, 25 men and 8 women) were included in the study. Most malignancies were located in the oropharynx. RESULTS: Among the 28 patients who scored normosmic or hyposmic at the beginning of the study, the mean decrease in TDI-score was 0.72 points (24.0-23.2) in the first cycle, 2.1 points (24.5-22.4) in the second cycle and 0.77 points (24.2-23.4) in the third cycle. The decrease during the second cycle was significant. Age (>55 years) had a significant (negative) influence in the first and the second cycles. Smoking only showed a tendency to decreased TDI-scores in chemotherapy. In-between consecutive cycles an increase in TDI-score was obvious (+1.0 points after the first and +1.5 points after the second cycle). CONCLUSION: Chemotherapy with cisplatin, 5 fluorouracil and docetaxel significantly affected sense of smell to a small extent. This effect was more pronounced in elderly patients and smokers. This fact must be taken into account as a possible additional negative effect in usually prevailing malnutrition in these patients. Furthermore, no cumulative effect of the administered therapeutic agents on olfaction could be proven during this study and recovery occurred within a 3-week period. PMID- 26264996 TI - Examining the phenotypic heterogeneity of early autism spectrum disorder: subtypes and short-term outcomes. AB - BACKGROUND: Phenotypic heterogeneity among toddlers presenting with ASD symptoms complicates diagnostic considerations and limits our ability to predict long-term outcomes. To address this concern, we sought to identify more homogeneous subgroups within ASD based on toddlers' clinical profiles in the second year of life, evaluating diagnostic stability and clinical outcomes within the subgroups 1-2 years later. METHODS: One hundred toddlers referred for suspected ASD underwent comprehensive assessments at 22 months (SD = 3) and 37 months (SD = 4). At 22 months, they were clustered based on symptom severity, developmental skills, and adaptive functioning. Diagnostic stability and clinical outcomes were evaluated within the clusters. RESULTS: Four clusters characterized by distinct clinical profiles at the time of the first diagnosis were identified. Diagnostic stability was excellent in 3 out of 4 clusters (93%-100%) and was lowest in the initially least affected cluster (85%). Autism symptom severity was stable, except for one group where it increased over time (16% of the sample). A large proportion of toddlers showed significant improvements in verbal and communication skills. Only a small group (17%) exhibited very low levels of functioning and limited gains over time. CONCLUSIONS: Diagnostic stability and developmental progression from the second to third year of life in toddlers with ASD vary depending on their initial early profiles of relative strengths and deficits. Although a small minority of toddlers with more complex clinical presentations may not retain their diagnoses by the age of three, most children continue to exhibit symptoms of autism. Despite limited improvements in symptom severity, many children show significant gains in verbal functioning. Only a small proportion of children (17%) exhibit very limited gains despite intensive intervention. These findings support continued efforts to examine determinants of developmental trajectories including factors mediating and moderating response to treatment. PMID- 26264997 TI - Creating pathways towards aromatic building blocks and fine chemicals. AB - Aromatic compounds represent a broad class of chemicals with a range of industrial applications, all of which are conventionally derived from petroleum feedstocks. However, owing to a diversity of available pathway precursors along with natural and engineered enzyme 'parts', microbial cell factories can be engineered to create alternative, renewable routes to many of the same aromatic products. Drawing from the latest tools and strategies in metabolic engineering and synthetic biology, such efforts are becoming an increasingly systematic practice, while continued efforts promise to open new doors to an ever-expanding range and diversity of renewable chemical and material products. This short review will highlight recent and notable achievements related for the microbial production of aromatic chemicals. PMID- 26264998 TI - Importance of Reporting the Gleason Score at the Positive Surgical Margin Site: Analysis of 4,082 Consecutive Radical Prostatectomy Cases. AB - PURPOSE: Since 2010 pathologists at our institution have routinely been documenting the Gleason score at the margin and length of the positive surgical margin after prostatectomy. In this study we evaluate how the Gleason score and positive surgical margin length correlate with the grade and adverse pathological characteristics of the final specimen, and whether the positive surgical margin Gleason score affects the risk of early biochemical recurrence. MATERIALS AND METHODS: A total of 4,082 consecutive patients undergoing radical prostatectomy and pelvic lymph node dissection between 2010 and 2014 for localized prostate cancer were included in the study, of whom 405 had a Gleason score of 7 or greater of the primary nodule and a positive surgical margin with the length and Gleason score recorded at the margin. Concordance rates between the Gleason score at the margin and the final pathological specimen were compared. Logistic regression models were used to predict the risk of unfavorable pathology. Cox proportional hazards models controlling for Gleason score, preoperative prostate specific antigen, pathological stage and adjuvant radiation were used to predict biochemical recurrence, and Kaplan-Meier estimates of recurrence-free survival were calculated by Gleason score. RESULTS: Among patients with positive margins biochemical recurrence was identified in 22% (vs 5.6% without positive margins), metastases in 3% (vs 0.5%) and adjuvant radiation in 30% (vs 4.1%). Mean followup was 22 months (range 12 to 48). The Gleason score at the positive surgical margin was the same as the final pathology specimen in 44% of patients, and a lower Gleason score in 56% of patients. A shorter positive surgical margin was independently associated with a lower Gleason score at the margin (p=0.02). Kaplan-Meier estimates demonstrated improved freedom from biochemical recurrence among patients with a lower Gleason score at the margin. In multivariate Cox models having a lower grade margin was associated with a decreased risk of biochemical recurrence (HR 0.50, OR 0.25-0.97). CONCLUSIONS: A lower Gleason score at the positive surgical margin is independently associated with a shorter margin length and a decreased risk of early biochemical recurrence. Thus, the Gleason score at the margin should be documented. PMID- 26264999 TI - The association between depressive symptoms and physical status including physical activity, aerobic and muscular fitness tests in children. AB - OBJECTIVES: The aims of the study were to explore the association between depressive symptoms (DS), physical activity (PA), aerobic and muscular fitness in a sample of children. METHODS: Four hundred and fifty-six schoolboys aged 7-11 year-old underwent standard anthropometry and various physical fitness tests (e.g., aerobic fitness, strength, speed, power, agility and flexibility). DS and PA were obtained by questionnaires. RESULTS: After adjustment for potential confounders (e.g., age, socioeconomic status and adiposity), PA was significantly and negatively related to DS (P < 0.05). Among the physical fitness tests, just time in one-mile run/walk was significantly related to DS (P < 0.05). CONCLUSION: Physical activity and aerobic fitness were significantly correlated with DS; however, no significant relationship was observed between DS and the muscular fitness tests in the children. PMID- 26265000 TI - Efficacy and safety of radiofrequency ablation and transcatheter arterial chemoembolization for treatment of hepatocellular carcinoma: A meta-analysis. AB - AIM: To investigate the efficacy and safety of radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE) for treatment of patients with hepatocellular carcinoma (HCC). METHODS: All eligible studies were collected from PubMed, the Cochrane Libraries and Embase. The evaluation indices included overall survival (OS) rate, recurrence-free survival rate, local tumor progression rate and major complications. All statistical analysis was performed by RevMan version 5.2 software. RESULTS: There were 21 studies with 3073 patients included in this meta-analysis. The RFA monotherapy was associated with higher 3- and 5-year OS rates (OR3-year = 2.33, 95% confidence interval [CI] = 1.34-4.05; OR5-year = 2.05, 95% CI = 1.48-2.85) compared with TACE alone. The combination of RFA and TACE was associated with higher 1-, 3- and 5-year OS rates (OR1-year = 1.94, 95% CI = 1.28-2.96; OR3-year = 1.56, 95% CI = 1.19-2.04; OR5-year = 1.53, 95% CI = 1.13-2.07) compared with RFA alone. CONCLUSION: The combination of TACE with RFA could obviously improve the short- and long-term survival rates and significantly provide a better prognosis for patients with intermediate-size HCC. RFA was associated with a higher long-term OS rate than that of TACE-treated patients with HCC. PMID- 26265001 TI - Evaluation of oxidized buckypaper as material for the solid phase extraction of cobalamins from milk: Its efficacy as individual and support sorbent of a hydrophilic-lipophilic balance copolymer. AB - This work describes a new analytical method for the determination of four cobalamins (adenosylcobalamin (AdoCbl), methylcobalamin (MeCbl), hydroxocobalamin (OHCbl) and cyanocobalamin (CNCbl)) in cow's milk. The extraction procedure is fast and based on dilution/protein precipitation of a milk sample with 50mM sodium acetate buffer (pH 4.6), followed by solid phase extraction (SPE) of the filtered supernatant. Relative recoveries higher than 60% have been obtained for all the cobalamins by combining two different types of sorbents in the same SPE cartridge: two disks of buckypaper (BP), a nanoporous felt composed of oxidized multiwalled carbon nanotubes (MWCNTs), separated by a Teflon frit from OASIS HLB (500mg), a hydrophilic-lipophilic balance copolymer. Before its use as sorbent, BP was characterized in terms of porosity, permeability, surface area, specific adsorption capacity and tested for a potential reuse after adequate chemical regeneration. The analysis of the extracts was performed by liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) on an analytical C18 column in less than 10min. After validation, the method was applied to the determination of the natural content of the four B12 homologues in cow's milk samples, providing data lacking in the literature. PMID- 26265002 TI - Instrument platforms for nano liquid chromatography. AB - The history of liquid chromatography started more than a century ago and miniaturization and automation are two leading trends in this field. Nanocolumn liquid chromatography (nano LC) and largely synonymous capillary liquid chromatography (capillary LC) are the most recent results of this process where miniaturization of column dimensions and sorbent particle size play crucial role. Very interesting results achieved in the research of extremely miniaturized LC columns at the end of the last century lacked distinctive raison d'etre and only advances in mass spectrometry brought a real breakthrough. Configuration of nano LC-electrospray ionization mass spectrometry (LC-ESI-MS) has become a basic tool in bioanalytical chemistry, especially in proteomics. This review discusses and summarizes past and current trends in the realization of nano liquid chromatography (nano LC) platforms. Special attention is given to the mobile phase delivery under nanoflow rates (isocratic, gradient) and sample injection to the nanocolumn. Available detection techniques applied in nano LC separations are also briefly discussed. We followed up the key themes from the original scientific reports over gradual improvements up to the contemporary commercial solutions. PMID- 26265003 TI - Band target entropy minimization for retrieving the information of individual components from overlapping chromatographic data. AB - Band target entropy minimization (BTEM) is a self-modeling curve resolution (SMCR) approach relying on non-negative criterion and minimization of Shannon entropy. In this study, BTEM algorithm was applied to retrieving the information of individual components from overlapping gas chromatography-mass spectrometry (GC-MS) data. The algorithm starts with dividing the whole data into bands along the retention time. In each band, singular value decomposition (SVD) is used to decompose the data into scores and loadings. Because the pure chromatographic signal possesses the lowest Shannon entropy, the chromatographic signal of each component can be constructed by optimizing the combination of the loadings with minimal Shannon entropy under non-negative criterion. To show the efficiency of the algorithm, a simulated four-component overlapping GC-MS data and an experimental GC-MS data of 18 organophosphorus pesticide mixture are investigated. The results show that both the chromatographic profiles and mass spectra of the components can be successfully extracted from the overlapping signals. PMID- 26265004 TI - Carboxyl modified magnetic nanoparticles coated open tubular column for capillary electrochromatographic separation of biomolecules. AB - Carboxyl modified magnetic nanoparticles (Fe3O4-COOH MNPs) coated open tubular (OT) columns were prepared for capillary electrochromatography. The Fe3O4-COOH MNPs coatings were constructed on the surface of positively charged poly(diallydimethylammonium chloride) (PDDA) modified capillaries through electrostatic self-assembly approach. The as-prepared PDDA@Fe3O4-COOH MNPs coated OT columns were characterized by scanning electron microscopy and electroosmotic flow measurement. The electrochromatographic characterization of the OT columns was evaluated by separation of amino acids, dipeptides and proteins. The influences of background solution pH, concentration, and organic modifier content on separation were investigated. The separation of these analytes was primarily based on the electrophoretic mechanism in combination with chromatographic mechanism. The Fe3O4-COOH MNPs coatings improved the separation resolution of these analytes due to their large surface area. Three variants of bovine serum albumin, two variants of beta-lactoglobulin and nine glycoisoforms of ovalbumin were successfully separated. The relative standard deviations of migration times of analytes representing run-to-run, day-to-day and column-to-column were less than 4.3%. Furthermore, the feasibility of the PDDA@Fe3O4-COOH MNPs coated OT column was verified by successful separation of acidic proteins in egg white. PMID- 26265005 TI - Optimising environmental risk assessments: Accounting for ecosystem services helps to translate broad policy protection goals into specific operational ones for environmental risk assessments. PMID- 26265006 TI - TRAIL+ monocytes and monocyte-related cells cause lung damage and thereby increase susceptibility to influenza-Streptococcus pneumoniae coinfection. AB - Streptococcus pneumoniae coinfection is a major cause of influenza-associated mortality; however, the mechanisms underlying pathogenesis or protection remain unclear. Using a clinically relevant mouse model, we identify immune-mediated damage early during coinfection as a new mechanism causing susceptibility. Coinfected CCR2(-/-) mice lacking monocytes and monocyte-derived cells control bacterial invasion better, show reduced epithelial damage and are overall more resistant than wild-type controls. In influenza-infected wild-type lungs, monocytes and monocyte-derived cells are the major cell populations expressing the apoptosis-inducing ligand TRAIL. Accordingly, anti-TRAIL treatment reduces bacterial load and protects against coinfection if administered during viral infection, but not following bacterial exposure. Post-influenza bacterial outgrowth induces a strong proinflammatory cytokine response and massive inflammatory cell infiltrate. Depletion of neutrophils or blockade of TNF-alpha facilitate bacterial outgrowth, leading to increased mortality, demonstrating that these factors aid bacterial control. We conclude that inflammatory monocytes recruited early, during the viral phase of coinfection, induce TRAIL-mediated lung damage, which facilitates bacterial invasion, while TNF-alpha and neutrophil responses help control subsequent bacterial outgrowth. We thus identify novel determinants of protection versus pathology in influenza-Streptococcus pneumoniae coinfection. PMID- 26265007 TI - Selective influence of Sox2 on POU transcription factor binding in embryonic and neural stem cells. AB - Embryonic stem cell (ESC) identity is orchestrated by co-operativity between the transcription factors (TFs) Sox2 and the class V POU-TF Oct4 at composite Sox/Oct motifs. Neural stem cells (NSCs) lack Oct4 but express Sox2 and class III POU-TFs Oct6, Brn1 and Brn2. This raises the question of how Sox2 interacts with POU-TFs to transcriptionally specify ESCs versus NSCs. Here, we show that Oct4 alone binds the Sox/Oct motif and the octamer-containing palindromic MORE equally well. Sox2 binding selectively increases the affinity of Oct4 for the Sox/Oct motif. In contrast, Oct6 binds preferentially to MORE and is unaffected by Sox2. ChIP-Seq in NSCs shows the MORE to be the most enriched motif for class III POU-TFs, including MORE subtypes, and that the Sox/Oct motif is not enriched. These results suggest that in NSCs, co-operativity between Sox2 and class III POU-TFs may not occur and that POU-TF-driven transcription uses predominantly the MORE cis architecture. Thus, distinct interactions between Sox2 and POU-TF subclasses distinguish pluripotent ESCs from multipotent NSCs, providing molecular insight into how Oct4 alone can convert NSCs to pluripotency. PMID- 26265009 TI - Methodological recommendations for a heartbeat detection-based measure of interoceptive sensitivity. AB - Heartbeat detection tasks are often used to measure cardiac interoceptive sensitivity-the ability to detect sensations from one's heart. However, there is little work to guide decisions on the optimum number of trials to use, which should balance reliability and power against task duration and participant burden. Here, 174 participants completed 100 trials of a widely used heartbeat detection task where participants attempt to detect whether presented tones occurred synchronously or asynchronously with their heartbeats. First, we quantified measurement reliability of the participant's accuracy derived from differing numbers of trials of the task using a correlation metric; we found that at least 40-60 trials were required to yield sufficient reliability. Next, we quantified power by simulating how the number of trials influenced the ability to detect a correlation between cardiac interoceptive sensitivity and other variables that differ across participants, including a variable measured from our sample (body mass index) as well as simulated variables of varying effect sizes. Using these simulations, we quantified the trade-offs between sample size, effect size, and number of trials in the heartbeat detection task such that a researcher can easily determine any one of these variables at given values of the other two variables. We conclude that using fewer than 40 trials is typically insufficient due to poor reliability and low power in estimating an effect size, although the optimal number of trials can differ by study. PMID- 26265010 TI - Effect of chronic urticaria on US patients: analysis of the National Health and Wellness Survey. AB - BACKGROUND: Chronic idiopathic (also called spontaneous) urticaria (CIU/CSU) is the most common form of chronic urticaria and has been associated with impairment to health outcomes, although the effect has never been assessed using a nationally representative sample in the United States. OBJECTIVES: To assess the burden of CIU/CSU from the patients' perspective in terms of health related quality of life, impairment to work and nonwork activities, and health care resource use. METHODS: Data were obtained from the US National Health and Wellness Survey. Current use of a prescription for the treatment of chronic hives was used as a proxy for CIU/CSU. Patients with CIU/CSU in the proxy group were matched 1:4 to respondents without chronic hives using survey year, sex, age, and race. Generalized linear models were adjusted for comorbidities, smoking, body mass index, and health insurance status. Outcome measures included the Medical Outcomes Study 12-Item and 36-Item Short Form Health Surveys; self-reported depression, anxiety, and sleep difficulties; the Work Productivity and Activity Impairment questionnaire, and health care resource use. RESULTS: After matching and adjustment for covariates, those currently using a prescription for chronic hives had mental component summary scores 5.7 points lower, physical component summary scores 6.5 points lower, and health utility scores 0.11 points lower than controls, as well as higher adjusted odds of reporting depression, anxiety, and sleep difficulties. Mean adjusted work impairment was approximately double in prescription-treated chronic hives relative to controls, as was frequency of health care visits. CONCLUSION: Chronic hives substantially affects quality of life, nonwork activities, capacity to work, and health care use, providing further evidence of a high burden of CIU/CSU across multiple health outcomes and unmet need for effective treatment. PMID- 26265008 TI - Integrative genomics positions MKRN1 as a novel ribonucleoprotein within the embryonic stem cell gene regulatory network. AB - In embryonic stem cells (ESCs), gene regulatory networks (GRNs) coordinate gene expression to maintain ESC identity; however, the complete repertoire of factors regulating the ESC state is not fully understood. Our previous temporal microarray analysis of ESC commitment identified the E3 ubiquitin ligase protein Makorin-1 (MKRN1) as a potential novel component of the ESC GRN. Here, using multilayered systems-level analyses, we compiled a MKRN1-centered interactome in undifferentiated ESCs at the proteomic and ribonomic level. Proteomic analyses in undifferentiated ESCs revealed that MKRN1 associates with RNA-binding proteins, and ensuing RIP-chip analysis determined that MKRN1 associates with mRNAs encoding functionally related proteins including proteins that function during cellular stress. Subsequent biological validation identified MKRN1 as a novel stress granule-resident protein, although MKRN1 is not required for stress granule formation, or survival of unstressed ESCs. Thus, our unbiased systems level analyses support a role for the E3 ligase MKRN1 as a ribonucleoprotein within the ESC GRN. PMID- 26265011 TI - A new, faster, and safe nasal provocation test method for diagnosing mite allergic rhinitis. AB - BACKGROUND: Diagnosing house dust mite (HDM) allergic rhinitis is difficult. The nasal provocation test (NPT) has been shown to be the most pertinent, but several methods are available. According to guidelines, the NPT requires a skin end-point titration and an objective measurement of nasal patency. Hence, NPT is time consuming and its use is limited. OBJECTIVE: To evaluate the sensitivity, specificity, and safety of a new, more rapid, and simple alternative NPT (NPT-R) to HDM. METHODS: Eighty-eight patients with from rhinitis (49 allergic to HDM and 39 controls with and without atopy) were included. Allergic rhinitis to HDM was confirmed by a "classic" NPT based on the Lebel score and rhinomanometry. After a period of 4 weeks, NPT-R was performed and only the clinical score was measured. RESULTS: The study population was young (mean +/- SD, 27.7 +/- 8.5 years old), composed mostly of women (61 vs 27 men), and 24% reported asthma. The sensitivity and specificity of NPT-R were 83.7% and 100%, respectively. The correlation between the NPTs was statistically significant (0.833, P < .0001, n = 88) and the 2 NPTs were completely safe. Performing NPT-R was more rapid (mean +/- SD, 22 +/- 8 minutes) than the classic NPT (97 +/- 20 minutes). CONCLUSION: The NPT-R is safe and easier and faster than the classic NPT. This new method appears to be a very useful tool in the diagnosis of HDM allergic rhinitis when the diagnosis is uncertain or before initiating immunotherapy. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT01485523. PMID- 26265012 TI - Multilevel selection theory and evidence: a critique of Gardner, 2015. AB - Gardner (2015) recently developed a model of a 'Genetical Theory of Multilevel Selection, which is a thoughtfully developed, but flawed model. The model's flaws appear to be symptomatic of common misunderstandings of the multi level selection (MLS) literature and the recent quantitative genetic literature. I use Gardner's model as a guide for highlighting how the MLS literature can address the misconceptions found in his model, and the kin selection literature in general. I discuss research on the efficacy of group selection, the roll of indirect genetic effects in affecting the response to selection and the heritability of group level traits. I also discuss why the Price multilevel partition should not be used to partition MLS, and why contextual analysis and, by association, direct fitness are appropriate for partitioning MLS. Finally, I discuss conceptual issues around questions concerning the level at which fitness is measured, the units of selection, and I present a brief outline of a model of selection in class-structured populations. I argue that the results derived from the MLS research tradition can inform kin selection research and models, and provide insights that will allow researchers to avoid conceptual flaws such as those seen in the Gardner model. PMID- 26265013 TI - Carnitine deficiency in children receiving continuous renal replacement therapy. AB - Carnitine deficiency is known to occur in chronic hemodialysis; however, the effect of continuous renal replacement therapy (CRRT) on carnitine homeostasis has not been studied. We hypothesized that children receiving CRRT are at risk for deficiency because of continuous removal, absent intake, decreased production, and comorbidities related to critical illness. Records of patients with acute kidney injury receiving CRRT at Children's National Health System between 2011 and 2014 were reviewed for total carnitine (TC), free carnitine (FC), feeding modality, severity of illness, and survival outcome. The proportion of carnitine-deficient patients at baseline, 1, 2, and >=3 weeks on CRRT were compared by chi-square, and relationships with other variables assessed by Pearson's correlation and logistic regression. The study group included 42 CRRT patients, age 7.9 + 1.1 years. At baseline, 30.7% and 35.7% of patients were TC and FC deficient. Within 1 week, 64.5% (P = 0.03) and 70% (P = 0.03) were TC and FC deficient, and prevalence of deficiency increased to 80% (P = 0.01) and 90% (P = 0.008) by 2 weeks; 100% of patients were TC and FC deficient after being on CRRT for >=3 weeks (P = 0.005 and P = 0.01, respectively, vs. baseline). TC and FC levels negatively correlated with days on CRRT (r = -0.39, P = 0.001 and r = 0.35, P = 0.005). Patients with TC and FC deficiency had 5.9 and 4.9 greater odds of death than those with normal levels (P = 0.02 and P = 0.03). Carnitine is significantly and rapidly depleted with longer time on CRRT, and carnitine deficiency is associated with increased mortality. Consequences of deficiency and benefits of supplementation in the pediatric CRRT population should be investigated. PMID- 26265014 TI - A Hierarchical Z-Scheme CdS-WO3 Photocatalyst with Enhanced CO2 Reduction Activity. AB - The development of an artificial photosynthetic system is a promising strategy to convert solar energy into chemical fuels. Here, a direct Z-scheme CdS-WO(3) photocatalyst without an electron mediator is fabricated by imitating natural photosynthesis of green plants. Photocatalytic activities of as-prepared samples are evaluated on the basis of photocatalytic CO(2) reduction to form CH(4) under visible light irradiation. These Z-scheme-heterostructured samples show a higher photocatalytic CO(2) reduction than single-phase photocatalysts. An optimized CdS WO(3) heterostructure sample exhibits the highest CH(4) production rate of 1.02 MUmol h(-1) g(-1) with 5 mol% CdS content, which exceeds the rates observed in single-phase WO(3) and CdS samples for approximately 100 and ten times under the same reaction condition, respectively. The enhanced photocatalytic activity could be attributed to the formation of a hierarchical direct Z-scheme CdS-WO(3) photocatalyst, resulting in an efficient spatial separation of photo-induced electron-hole pairs. Reduction and oxidation catalytic centers are maintained in two different regions to minimize undesirable back reactions of the photocatalytic products. The introduction of CdS can enhance CO(2) molecule adsorption, thereby accelerating photocatalytic CO(2) reduction to CH(4). This study provides novel insights into the design and fabrication of high-performance artificial Z-scheme photocatalysts to perform photocatalytic CO(2) reduction. PMID- 26265015 TI - Cohort study of malignancies and hospitalized infectious events in treated and untreated patients with psoriasis and a general population in the United States. AB - BACKGROUND: Psoriasis is associated with risk of malignancy. Some psoriasis treatments may increase the risk of hospitalized infectious events (HIEs). OBJECTIVES: To evaluate rates of malignancies and HIEs in patients with psoriasis. METHODS: This retrospective cohort study utilized data from MarketScan((r)) databases. Cohorts included adult general population (GP), patients with psoriasis, and patients with psoriasis treated with nonbiologics, adalimumab, etanercept, infliximab or phototherapy. Outcomes included incidence rates (IRs) per 10 000 person-years observation (PYO) for all malignancies excluding nonmelanoma skin cancer (NMSC), lymphoma, NMSC, and per 10 000 person years of exposure (PYE) for HIEs. RESULTS: Incidence rates [95% confidence interval (CI)] for all malignancies except NMSC were 129 (127-130) and 142 (135 149) for GP (PYO = 51 071 587) and psoriasis (PYO = 119 432) cohorts, respectively; 10.9 (10.5-11.3) and 12.9 (10.9-14.8) for lymphoma; and 145 (144 147) and 180 (173-188) for NMSC. Rates for all malignancies excluding NMSC were similar among treatments but variable for lymphoma and NMSC. IRs (95% CI) for HIEs were 332 (256-408) for the nonbiologic cohort (PYE = 3528); 288 (206-370) for etanercept (PYE = 6563); 325 (196-455) for adalimumab (PYE = 2772); 521 (278 765) for infliximab (PYE = 1058); and 334 (242-427) for phototherapy (PYE = 1797). IRs for HIEs were lowest for etanercept and higher in patients on baseline systemic corticosteroids across treatment cohorts. CONCLUSIONS: Malignancy rates were higher in patients with psoriasis than the GP, but these treatments did not appear to increase malignancy risk. PMID- 26265016 TI - Breastfeeding and childhood acute otitis media: a systematic review and meta analysis. AB - AIM: To synthesise the evidence on the association between duration and exclusivity of breastfeeding and the risk of acute otitis media (AOM). METHODS: Systematic review and meta-analysis following searching of PubMed, CINAHL and EMBASE electronic databases. RESULTS: Twenty-four studies, all from the USA or Europe, met the inclusion criteria. In the pooled analyses, any form of breastfeeding was found to be protective for AOM in the first 2 years of life. Exclusive breastfeeding for the first 6 months was associated with the greatest protection (OR 0.57 95% CI 0.44, 0.75), followed by 'more vs less' breastfeeding (OR 0.67; 0.59, 0.76) and 'ever vs never' breastfeeding (OR 0.67; 0.56, 0.80). CONCLUSION: This systematic review and meta-analysis provides evidence that breastfeeding protects against AOM until 2 years of age, but protection is greater for exclusive breastfeeding and breastfeeding of longer duration. Exclusive breastfeeding during the first 6 months was associated with around a 43% reduction in ever having AOM in the first 2 years of life. After 2 years of age, there is no evidence that breastfeeding protects against AOM; however, there were few studies and the evidence quality was low. PMID- 26265017 TI - Effect of different combinations of soybean-maize silage on its chemical composition, nutrient intake, degradability, and performance of Pelibuey lambs. AB - Sheep raising in the state of Guerrero, Mexico, is a primary activity that is worth about US$3,251,931 annually. The objective of the present study was to evaluate the chemical composition, degradability, nutrient intake, and animal performance of Pelibuey lambs fed on different combinations of maize-soybean silages. Twenty-one combinations of maize silage (MS) and soybean silage (SS) were evaluated at day 45 post-ensiling; in each combination, MS was replaced by 5 % of SS. The 21 combinations were analysed for crude protein (CP) and chemical composition. In order to obtain a statistical criterion of potential treatments for the animal feeding test, a cluster analysis was performed based on the CP contents of all combinations at day 45 post-ensiling. From cluster analysis, four treatments were selected T1 = 100-0 % (MS/SS), T8 = 65-35 %, T12 = 45-55 %, and T16 = 25-75 %. Results indicated that cluster analysis was useful for identifying the potential treatments for animal feeding based on the crude protein content. The dry matter (DM), organic matter (OM), and acid detergent lignin (ADL) contents did not declined significantly (P > 0.05) during the fermentation of silages but CP content decreased from day 0 to 45 post-ensiling. The treatment with the highest estimated microbial crude protein synthesis was T8 and it showed the highest metabolizable energy intake, high feed efficiency with a forage concentrate ratio of 84:16. PMID- 26265018 TI - Prophylactic and Therapeutic Potential of Acetyl-L-carnitine against Acetaminophen-Induced Hepatotoxicity in Mice. AB - Prophylactic and therapeutic effects of acetylcarnitine against acetaminophen induced hepatotoxicity were studied in mice. To evaluate the prophylactic effects of acetylcarnitine, mice were supplemented with acetylcarnitine (2 mmol/kg/day per oral (p.o.) for 5 days) before a single dose of acetaminophen (350 mg/kg intraperitoneal (i.p.)). Animals were sacrificed 6 h after acetaminophen injection. Acetaminophen significantly increased the markers of liver injury, hepatic reactive oxygen species, and nitrate/nitrite, and decreased hepatic glutathione (GSH) and the antioxidant enzymes. Acetylcarnitine supplementation resulted in reversal of all biochemical parameters toward the control values. To explore the therapeutic effects of acetylcarnitine, mice were given a single dose of acetylcarnitine (0.5, 1, and 2 mmol/kg p.o.) 1.5 h after acetaminophen. Animals were sacrificed 6 h after acetaminophen. Acetylcarnitine administration resulted in partial reversal of liver injury only at 2 mmol/kg p.o. At equimolar doses, N-acetylcystiene was superior as therapeutic agent to acetylcarnitine. However, acetylcarnitine potentiated the effect of N-acetylcystiene in the treatment of acetaminophen toxicity. PMID- 26265023 TI - Case report of an acute foreign object airway obstruction resolved by back blows alone. PMID- 26265022 TI - Exploring preferences for domain-specific goal management in patients with polyarthritis: what to do when an important goal becomes threatened? AB - Usually priorities in goal management--intended to minimize discrepancies between a given and desired situation--are studied as person characteristics, neglecting possible domain-specific aspects. However, people may make different decisions in different situations depending on the importance of the personal issues at stake. Aim of the present study therefore was to develop arthritis-related vignettes to examine domain-specific goal management and to explore patients' preferences. Based on interviews and literature, situation-specific hypothetical stories were developed in which the main character encounters a problem with a valued goal due to arthritis. Thirty-one patients (61 % female, mean age 60 years) evaluated the face validity of the newly developed vignettes. Secondly, 262 patients (60 % female, mean age 63 years) were asked to come up with possible solutions for the problems with attaining a goal described in a subset of the vignettes. Goal management strategies within the responses and the preference for the various strategies were identified. The 11 developed vignettes in three domains were found to be face-valid. In 90 % of the responses, goal management strategies were identified (31 % goal maintenance, 29 % goal adjustment, 21 % goal disengagement, and 10 % goal re-engagement). Strategy preference was related to domains. Solutions containing goal disengagement were the least preferred. Using vignettes for measuring domain-specific goal management appears as valuable addition to the existing questionnaires. The vignettes can be used to study how patients with arthritis cope with threatened goals in specific domains from a patient's perspective. Domain-specific strategy preference emphasizes the importance of a situation-specific instrument. PMID- 26265024 TI - Prevalent emm types and superantigen gene patterns of group A Streptococcus in Thailand. AB - Group A Streptococcus (GAS) are globally distributed bacterial pathogens. We examined the emm genotypes, which are important indicators of virulence, of 349 clinical GAS isolates collected using two surveillance systems, i.e. Invasive Bacterial Infection Surveillance (IBIS) from 2010 to 2011 (234 isolates) and routine surveillance of clinically isolated bacteria from various hospitals during 1996-2011 (115 isolates) in Thailand. The major emm genotypes in IBIS samples were emm44 (12.0%), emm104 (6.8%), emm22 (5.6%), and emm81 (5.6%), whereas only one isolate (0.4%) had the emm1 genotype, which is significantly more common in invasive cases in the Western world. In samples collected during routine surveillance, emm238 (10.4%), emm44 (8.7%), and emm165 (7.0%) were dominant. The major superantigen gene profiles were similar between the groups, and 30.1% of isolates did not possess the phage-encoded superantigens (speA, speC, speH, speI, speK, speL, speM, ssa). Although most isolates exhibited limited gene profiles, emm44 isolates had highly variable gene profiles (15 patterns). We conclude that emm44 is the predominant GAS genotype in Thailand, and isolates varied in superantigen gene profiles. PMID- 26265026 TI - Rural-Urban Differences in Perceptions of Child Overweight Among Children and Adolescents, Their Guardians and Health Care Professionals in the United States. AB - RESEARCH OBJECTIVE: Children and adolescents residing in rural environments with higher prevalence of an overweight population may develop inaccurate perceptions of a healthy weight. This study examines rural-urban differences in perceptions of child overweight among overweight (85 <= BMI percentile < 95) and obese children (BMI percentile >= 95), their guardians and health care providers (HCPs), and children's concomitant weight control. METHODS: The cross-sectional study was based on the 2005-2010 NHANES data (1,844 overweight and obese children and adolescents, aged 8-15 years). Rurality was defined using the 2003 RUCC. The weight status was based on the standardized measures of children's height and weight. Children reported whether they considered themselves overweight and whether they were trying to lose weight. Proxy respondents (ie, guardians) reported whether they considered their child to be overweight and whether an HCP had ever told them their child was overweight. Weighted percentages and predicted probabilities from multivariable logistic regressions were calculated, accounting for the complex, multistage, probability sampling design and nonresponse. FINDINGS: Rural residents comprised 18.8% of the study population; 41.8% of them were overweight and 58.2% were obese compared to 46.7% and 53.3% of urban peers, respectively. Misperceptions of children's weight status were 11.3 and 6.0 percentage points higher in rural children and their guardians, respectively. Recall of an HCP identification of child overweight was 6.3 percentage points lower among rural versus urban guardians. CONCLUSION: Obesity prevention efforts may be fostered by improving accuracy of child overweight perceptions. This may be particularly impactful in rural settings, where weight misperceptions are high. PMID- 26265025 TI - The body composition phenotype of Irish adults aged 18-81 years. AB - BACKGROUND: Regional distribution of adiposity and lean tissue mass are predictors of health risk that cannot be defined by body mass index but can be attained by dual-energy X-ray absorptiometry (DXA). Age and sex-related adult ranges of whole-body and regional adiposity and lean tissue are not available for Irish men and women. AIMS: The aim of this study was to construct a DXA-based body composition profile of Irish adults, focusing on age- and sex-related difference in total and regional adiposity and lean tissue mass. METHODS: The study population comprised a convenience sample of 1606 participants, aged 18-81 years participating in the University of Limerick Body Composition study. Data were analysed to construct stature-normalised indices of body fat mass (BFMI), site-specific visceral adiposity, lean tissue mass (LTMI) and appendicular lean tissue mass (ALTMI). RESULTS: Compared to the young adult (18-29 years), BFMI was higher in women (p < 0.001) but plateaued in men aged >50 years. For men, age related difference in LTMI was not evident but ALTMI was significantly lower in those >50 years. For women, there was evidence of significantly lower LTMI with advancing age and, similar to men, significantly lower ALTMI in those >50 years. CONCLUSIONS: These data provide an insight into the age-related anthropometric phenotype of Irish adults. Centile data have been constructed that provide informative data of the age and sex-specific range of adiposity and lean tissue mass. These data may assist in identification of those at risk of aberrant, body composition-related disease. PMID- 26265027 TI - Birth of the Allostatic Model: From Cannon's Biocracy to Critical Physiology. AB - Physiologists and historians are still debating what conceptually differentiates each of the three major modern theories of regulation: the constancy of the milieu interieur, homeostasis and allostasis. Here I propose that these models incarnate two distinct regimes of politization of the life sciences. This perspective leads me to suggest that the historicization of physiological norms is intrinsic to the allostatic model, which thus divides it fundamentally from the two others. I analyze the allostatic model in the light of the Canguilhemian theory, showing how the former contributed to the development of a critical epistemology immune to both naturalist essentialism and social constructivism. With a unique clarity in the history of physiology, allostasis gives us a model of the convergence of historical epistemology and scientific practice. As such it played a key role in codifying the epistemological basis of certain current research programs that, in the fields of social epidemiology and feminist neuroscience, promote what we name here a critical physiology. PMID- 26265028 TI - Dementia, medication and transitions of care. AB - BACKGROUND: Persons with dementia (PWD) often have complex medication regimens and are at risk of medication problems during the multiple transitions of care experienced as the condition progresses. OBJECTIVES: To explore medication processes in acute care episodes and care transitions for PWD and to make recommendations to improve practice. METHOD: Semi-structured interviews were conducted by two pharmacy researchers from a focused purposive sample of fifty one participants (carers, health professionals, Alzheimer's Australia staff) from urban and rural Australia. After written consent, the interviews were audio recorded then transcribed verbatim for face-to-face interviews, or notes were taken during the interview if conducted by telephone. The transcripts were checked for accuracy by the pharmacy researchers. Thematic analysis of the data was undertaken independently by the two researchers to reduce bias and any disagreements were resolved by discussion. RESULTS: Themes identified were: medication reconciliation; no modified planning for care transitions; underutilization of information technology; multiple prescribers; residential aged care facilities; and medication reviews by pharmacists. Sub themes were: access to appropriate staff; identification of dementia; dose administration aids; and staff training. CONCLUSIONS: Medication management is sub-optimal for PWD during care transitions and may compromise safety. Suggested improvements included: increased involvement of pharmacists in care transitions; outreach or transitional health care professionals; modified planning for care transitions for individuals over 80 years; co-ordinated electronic records; structured communication; and staff training. PMID- 26265029 TI - Structural Characteristics of Migrant Farmworkers Reporting a Relationship with a Primary Care Physician. AB - Migrant farmworkers are disproportionately affected by many adverse health conditions, but access healthcare sparingly. This study of migrant farmworkers examined the distribution and general characteristics associated with having access to healthcare. Access to healthcare was measured by asking whether the participants (N = 413) had a primary care physician. Majority of participants did not have a primary care physician. Female migrant workers (AOR = 2.823 CI: 1.575 4.103) with insurance (AOR = 6.183 CI: 4.956-11.937) who lived at study site for more than 5 years (AOR = 2.728 CI: 1.936-7.837) and born in the United States (AOR = 2.648 CI: 1.373-3.338) had greater odds to have a primary care physician than recent male migrants without insurance who were born outside United States. There is a need to focus on Community Health Centers and Migrant Health Centers in tailoring their services and to widen the implementation and improve funding of Accountable Care Organizations to improve access to care of migrant farmworkers. PMID- 26265030 TI - Inappropriate sexual behaviour in adolescents with autism spectrum disorder: what education is recommended and why. AB - AIM: Autism spectrum disorder (ASD) is a neurodevelopmental disorder impairing social skills and communication. Adolescents with ASD have sexual needs, but may not understand their physical and emotional development resulting in inappropriate sexual behaviour. The aim of this review is to describe the type of inappropriate behaviour that presents in these adolescents, explain why such behaviours occur, suggest what education is suitable and identify current gaps in research. METHOD: The databases EMBASE, OVID MEDLINE and PSYCINFO were searched for relevant articles. In total, 5241 articles were found, with an additional 15 sources found via soft searches, of which 42 met inclusion criteria and were subsequently reviewed. RESULTS: Sexual behaviours that occur in these adolescents with ASD include hypermasturbation, public masturbation, inappropriate romantic gestures, inappropriate arousal and exhibitionism. Such behaviours are thought to be caused via a lack of understanding of normal puberty, the absence of appropriate sex education, the severity of their ASD and other associated problems. It is suggested that individualized, repetitive education should be started from an early age in an accessible form. Social skills development is also important before more technical aspects of sex education are taught. CONCLUSION: Despite being such a common problem for schools, institutions and families to manage, it is surprising how sparse literature is particularly regarding why inappropriate behaviour occurs and what education is effective. PMID- 26265031 TI - Recent developments in stable isotope dilution assays in mycotoxin analysis with special regard to Alternaria toxins. AB - Stable isotope dilution assays (SIDAs) are becoming ever commoner in mycotoxin analysis, and the number of synthesized or commercially available isotopically labelled compounds has greatly increased in the 7 years since our last review dealing with this topic. Thus, this review is conceived as an update for new applications or improvements of SIDAs for compounds discussed earlier, but the main focus is on newly introduced labelled substances and the development of SIDAs for, for example, fusarin C, moniliformin or the enniatins. Mycotoxin research has concentrated on the emerging group of Alternaria toxins in recent years, and a series of SIDAs have been developed, including ones for tenuazonic acid, alternariol, altertoxins and tentoxin that are discussed in detail in this review. Information about synthetic routes, isotopic purity and mass spectrometric characterization of labelled compounds is given, as well as about the development and validation of SIDAs and their application to foods, feeds or biological samples. As the number of commercially available labelled standards is increasing continuously, a general tendency for the use of analytical methods based on liquid chromatography coupled with mass spectrometry capable of identifying a series of mycotoxins simultaneously ("multimethods") and using one or more labelled internal standards can be observed. An overview of these applications is given, thus demonstrating that SIDAs are increasingly being used in routine analysis. PMID- 26265032 TI - Analysis and calibration of stage axial vibration for synchrotron radiation nanoscale computed tomography. AB - Synchrotron radiation nanoscale computed tomography (SR nano-CT) is a powerful analysis tool and can be used to perform chemical identification, mapping, or speciation of carbon and other elements together with X-ray fluorescence and X ray absorption near edge structure (XANES) imaging. In practical applications, there are often challenges for SR nano-CT due to the misaligned geometry caused by the sample stage axial vibration. It occurs quite frequently because of experimental constraints from the mechanical error of manufacturing and assembly and the thermal expansion during the time-consuming scanning. The axial vibration will lead to the structure overlap among neighboring layers and degrade imaging results by imposing artifacts into the nano-CT images. It becomes worse for samples with complicated axial structure. In this work, we analyze the influence of axial vibration on nano-CT image by partial derivative. Then, an axial vibration calibration method for SR nano-CT is developed and investigated. It is based on the cross correlation of plane integral curves of the sample at different view angles. This work comprises a numerical study of the method and its experimental verification using a dataset measured with the full-field transmission X-ray microscope nano-CT setup at the beamline 4W1A of the Beijing Synchrotron Radiation Facility. The results demonstrate that the presented method can handle the stage axial vibration. It can work for random axial vibration and needs neither calibration phantom nor additional calibration scanning. It will be helpful for the development and application of synchrotron radiation nano-CT systems. PMID- 26265033 TI - Dawning of a new era for acute stroke therapy. PMID- 26265034 TI - Altered functional connectivity density in major depressive disorder at rest. AB - Major depressive disorder is characterized by abnormal brain connectivity at rest. Currently, most studies investigating resting-state activity rely on a priori restrictions on specific networks or seed regions, which may bias observations. We hence sought to elicit functional alterations in a hypothesis free approach. We applied functional connectivity density (FCD) to identify abnormal connectivity for each voxel in the whole brain separately. Comparing resting-state fMRI in 21 MDD patients and 23 matched healthy controls, we identified atypical connections for regions exhibiting abnormal FCD and compared our results to those of an independent component analysis (ICA) on networks previously investigated in MDD. Patients showed reduced FCD in mid-cingulate cortex (MCC) and increased FCD in occipital cortex (OCC). These changes in global FCD were driven by abnormal local connectivity changes and reduced functional connectivity (FC) toward the left amygdala for MCC, and increased FC toward the right supplementary motor area for OCC. The altered connectivity was not reflected in ICA comparison of the salience and visual networks. Abnormal FC in MDD is present in cingulate and OCC in terms of global FCD. This converges with previous structural and metabolic findings; however, these particular changes in connectivity would not have been identified using canonical seed regions or networks. This implies the importance of FC measures in the investigation of brain pathophysiology in depression. PMID- 26265035 TI - Genotyping of a family with a novel deleterious DPYD mutation supports the pretherapeutic screening of DPD deficiency with dihydrouracil/uracil ratio. AB - Despite the growing evidence that dihydropyrimidine dehydrogenase deficiency (DPD, encoded by the DPYD gene) confers a higher risk of developing severe toxicity, most patients are not screened for DPD deficiency before fluoropyrimidine treatment. We report here the genetic and phenotypic analyses of DPD in a family related to a patient who died after a first cycle of 5 fluorouracil and in 15 additional retrospective patients having a partial DPD deficiency (as measured by plasma dihydrouracil/uracil ratio). The patient with lethal toxicity was found to be a compound heterozygote for two DPYD mutations: a novel 8-bp duplication (c.168_175dupGAATAATT, p.Phe59Ter) and c.1679T>G (Ile560Ser). The patient's dihydrouracil/uracil ratio indicates complete DPD deficiency. The novel mutation was found in two members of the patient's family. Deleterious DPYD mutations were identified in 9 out of the 15 patients. The relationship between genotype and dihydrouracil/uracil values in the 22 patients of the present study was significant (P = 0.01). PMID- 26265037 TI - Use of multi-InDels as novel markers to analyze 13 X-chromosome haplotype loci for forensic purposes. AB - Many studies have been proposed to identify insertion/deletion (InDel) polymorphisms in humans for forensic genetic studies. However, the discriminatory power of InDels is limited by the poor polymorphisms of diallelic markers. To improve their discriminatory power, we developed multi-InDel, a novel autosomal marker comprising more than two InDel loci that are tightly linked by their physical position and combined into a specific marker by a pair of PCR primers. This strategy gives at least three haplotypes for each multi-InDel marker. Such markers can be potentially very useful in forensic applications. In this study, we focused on multi-InDel markers located on X chromosome (ChrX). A multiplex system with 13 multi-InDel markers, including 28 InDel loci in ChrX, was developed. To validate the multi-InDel panel, the haplotype distribution in a population sample and in a set of pedigrees was investigated. This study demonstrates usefulness of these markers for individual identification and relationship studies. We highlight the fact that the multi-InDel markers located on ChrX can provide new supporting information for complex kinship testing. PMID- 26265036 TI - Genome-wide association study of warfarin maintenance dose in a Brazilian sample. AB - AIM: Extreme discordant phenotype and genome-wide association (GWA) approaches were combined to explore the role of genetic variants on warfarin dose requirement in Brazilians. METHODS: Patients receiving low (<= 20 mg/week; n = 180) or high stable warfarin doses (>= 42.5 mg/week; n = 187) were genotyped with Affymetrix Axiom((r)) Biobank arrays. Imputation was carried out using data from the combined 1000 Genomes project. RESULTS: Genome-wide signals (p <= 5 * 10(-8)) were identified in the well-known VKORC1 (lead SNP, rs749671; OR: 20.4; p = 1.08 * 10(-33)) and CYP2C9 (lead SNP, rs9332238, OR: 6.8 and p = 4.4 * 10(-13)) regions. The rs9332238 polymorphism is in virtually perfect LD with CYP2C9*2 (rs1799853) and CYP2C9*3 (rs1057910). No other genome-wide significant regions were identified in the study. CONCLUSION: We confirmed the important role of VKORC1 and CYP2C9 polymorphisms in warfarin dose. Original submitted 14 January 2015; Revision submitted 26 May 2015. PMID- 26265038 TI - First tobacco product tried: associations with smoking status and demographics among college students. AB - INTRODUCTION: As the tobacco market expands, so too have the opportunities for youth to be introduced to nicotine. The goal of this study was to identify product choice for initial tobacco trial, correlates associated with product choice, and the relationship between first product and current cigarette smoking among college students. METHODS: A cross-sectional web survey of 3146 first-year students at 11 universities in North Carolina and Virginia was conducted in fall 2010. RESULTS: Weighted prevalence of ever use of tobacco was 48.6%. Cigarettes were the most common first product (37.9%), followed by cigars (29.3%), hookahs (24.6%), smokeless tobacco (6.1%), and bidis/kreteks (2.2%). Two thirds (65%) of current smokers initiated with cigarettes, but 16.4% started with cigars, 11.1% with hookahs, 5.7% with smokeless, and 1.7% with bidis/kreteks. Females were more likely to report their first product was cigarettes and hookahs, while males were more likely to start with cigars and smokeless tobacco. Compared to those whose first product trial occurred after the age of 18, younger age of initiation (17years or younger) was associated with cigarettes and smokeless as first products, while older age of initiation (18 or older) was associated with starting with hookahs and cigars. Dual or poly tobacco use was more common among those who initiated with hookahs and smokeless tobacco. CONCLUSIONS: While over a third of students used cigarettes first, two thirds started with a non-cigarette product. Just about a third of current cigarette smokers initiated with a non cigarette product, suggesting that those non-cigarette products may have facilitated escalation to cigarettes. PMID- 26265039 TI - On the Fine Isotopic Distribution and Limits to Resolution in Mass Spectrometry. AB - Mass spectrometry enables the study of increasingly larger biomolecules with increasingly higher resolution, which is able to distinguish between fine isotopic variants having the same additional nucleon count, but slightly different masses. Therefore, the analysis of the fine isotopic distribution becomes an interesting research topic with important practical applications. In this paper, we propose the comprehensive methodology for studying the basic characteristics of the fine isotopic distribution. Our approach uses a broad spectrum of methods ranging from generating functions--that allow us to estimate the variance and the information theory entropy of the distribution--to the theory of thermal energy fluctuations. Having characterized the variance, spread, shape, and size of the fine isotopic distribution, we are able to indicate limitations to high resolution mass spectrometry. Moreover, the analysis of "thermorelativistic" effects (i.e., mass uncertainty attributable to relativistic effects coupled with the statistical mechanical uncertainty of the energy of an isolated ion), in turn, gives us an estimate of impassable limits of isotopic resolution (understood as the ability to distinguish fine structure peaks), which can be moved further only by cooling the ions. The presented approach highlights the potential of theoretical analysis of the fine isotopic distribution, which allows modeling the data more accurately, aiming to support the successful experimental measurements. PMID- 26265040 TI - Ion Yields in the Coupled Chemical and Physical Dynamics Model of Matrix-Assisted Laser Desorption/Ionization. AB - The Coupled Chemical and Physical Dynamics (CPCD) model of matrix assisted laser desorption ionization has been restricted to relative rather than absolute yield comparisons because the rate constant for one step in the model was not accurately known. Recent measurements are used to constrain this constant, leading to good agreement with experimental yield versus fluence data for 2,5 dihydroxybenzoic acid. Parameters for alpha-cyano-4-hydroxycinnamic acid are also estimated, including contributions from a possible triplet state. The results are compared with the polar fluid model, the CPCD is found to give better agreement with the data. PMID- 26265041 TI - Software Analysis of Uncorrelated MS1 Peaks for Discovery of Post-Translational Modifications. AB - The goal in proteomics to identify all peptides in a complex mixture has been largely addressed using various LC MS/MS approaches, such as data dependent acquisition, SRM/MRM, and data independent acquisition instrumentation. Despite these developments, many peptides remain unsequenced, often due to low abundance, poor fragmentation patterns, or data analysis difficulties. Many of the unidentified peptides exhibit strong evidence in high resolution MS(1) data and are frequently post-translationally modified, playing a significant role in biological processes. Proteomics Workbench (PWB) software was developed to automate the detection and visualization of all possible peptides in MS(1) data, reveal candidate peptides not initially identified, and build inclusion lists for subsequent MS(2) analysis to uncover new identifications. We used this software on existing data on the autophagy regulating kinase Ulk1 as a proof of concept for this method, as we had already manually identified a number of phosphorylation sites Dorsey, F. C. et al (J. Proteome. Res. 8(11), 5253-5263 (2009)). PWB found all previously identified sites of phosphorylation. The software has been made freely available at http://www.proteomicsworkbench.com . Graphical Abstract ?. PMID- 26265042 TI - Lipoprotein lipase is an important modulator of lipid uptake and storage in hypothalamic neurons. AB - LPL is the rate-limiting enzyme for uptake of TG-derived FFA in peripheral tissues, and the enzyme is expressed in the brain and CNS. We previously created a mouse which lacks neuronal LPL. This animal becomes obese on a standard chow, and we observed reduced lipid uptake in the hypothalamus at 3 months preceding obesity. In our present study, we replicated the animal phenotype in an immortalized mouse hypothalamic cell line (N41) to examine how LPL affects expression of AgRP as well as entry and storage of lipids into neurons. We show that LPL is able to modulate levels of the orexigenic peptide AgRP. LPL also exerts effects on lipid uptake into culture neurons, and that uptake of neutral lipid can be enhanced even by mutant LPL lacking catalytic activity. N41 cells also accumulate neutral lipid in droplets, and this is at least in part regulated by LPL. These data in addition to those published in mice with neuron-specific deletion of LPL suggest that neuronal LPL is an important regulator of lipid homeostasis in neurons and that alterations in LPL levels may have important effects on systemic metabolism and neuronal lipid biology. PMID- 26265043 TI - Pharmacokinetics and pharmacodynamics of orally administered acetylenic tricyclic bis(cyanoenone), a highly potent Nrf2 activator with a reversible covalent mode of action. AB - The acetylenic tricyclic bis(cyanoenone) TBE-31 is a highly potent cysteine targeting compound with a reversible covalent mode of action; its best characterized target being Kelch-like ECH-associated protein-1 (Keap1), the cellular sensor for oxidants and electrophiles. TBE-31 reacts with cysteines of Keap1, impairing its ability to target nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) for degradation. Consequently, Nrf2 accumulates and orchestrates cytoprotective gene expression. In this study we investigated the pharmacokinetic and pharmacodynamic properties of TBE-31 in C57BL/6 mice. After a single oral dose of 10 MUmol/kg (~200 nmol/animal), the concentration of TBE-31 in blood exhibited two peaks, at 22.3 nM and at 15.5 nM, 40 min and 4 h after dosing, respectively, as determined by a quantitative stable isotope dilution LC-MS/MS method. The AUC0-24h was 195.5 h/nmol/l, the terminal elimination half-life was 10.2 h, and the kel was 0.068 h(-1). To assess the pharmacodynamics of Nrf2 activation by TBE-31, we determined the enzyme activity of its prototypic target, NAD(P)H: quinone oxidoreductase 1 (NQO1) and found it elevated by 2.4- and 1.5 fold in liver and heart, respectively. Continuous feeding for 18 days with diet delivering the same daily doses of TBE-31 under conditions of concurrent treatment with the immunosuppressive agent azathioprine had a similar effect on Nrf2 activation without any indications of toxicity. Together with previous reports showing the cytoprotective effects of TBE-31 in animal models of carcinogenesis, our results demonstrate the high potency, efficacy and suitability for chronic administration of cysteine targeting reversible covalent drugs. PMID- 26265044 TI - MicroRNA-17-mediated down-regulation of apoptotic protease activating factor 1 attenuates apoptosome formation and subsequent apoptosis of cardiomyocytes. AB - Heart diseases such as myocardial infarction (MI) can damage individual cardiomyocytes, leading to the activation of cell death programs. The most scrutinized type of cell death in the heart is apoptosis, and one of the key events during the propagation of apoptotic signaling is the formation of apoptosomes, which relay apoptotic signals by activating caspase-9. As one of the major components of apoptosomes, apoptotic protease activating factor 1 (Apaf-1) facilitates the formation of apoptosomes containing cytochrome c (Cyto-c) and deoxyadenosine triphosphate (dATP). Thus, it may be possible to suppress the activation of the apoptotic program by down-regulating the expression of Apaf-1 using miRNAs. To validate this hypothesis, we selected a number of candidate miRNAs that were expected to target Apaf-1 based on miRNA target prediction databases. Among these candidate miRNAs, we empirically identified miR-17 as a novel Apaf-1-targeting miRNA. The delivery of exogenous miR-17 suppressed Apaf-1 expression and consequently attenuated formation of the apoptosome complex containing caspase-9, as demonstrated by co-immunoprecipitation and immunocytochemistry. Furthermore, miR-17 suppressed the cleavage of procaspase-9 and the subsequent activation of caspase-3, which is downstream of activated caspase-9. Cell viability tests also indicated that miR-17 pretreatment significantly prevented the norepinephrine-induced apoptosis of cardiomyocytes, suggesting that down-regulation of apoptosome formation may be an effective strategy to prevent cellular apoptosis. These results demonstrate the potential of miR-17 as an effective anti-apoptotic agent. PMID- 26265045 TI - AMPK dependent protective effects of metformin on tumor necrosis factor-induced apoptotic liver injury. AB - Tumor necrosis factor alpha (TNF-alpha)-induced cellular apoptosis represents a common pathological mechanism underlying the progression of various liver disorders. Recently studies revealed that the anti-diabetic metformin provided protective benefits in several animal models of liver injury. In the present study, the potential modulatory effects of metformin on TNF-alpha-dependent apoptotic liver damage was investigated in mice with TNF-alpha/d-galactosamine (D Gal)-induced liver injury. The results indicated that treatment with metformin significantly suppressed the elevation of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the activation of caspase cascade and the induction of cleaved caspase-3. Morphological analysis showed that metformin alleviated histopathological abnormalities and reduced TUNEL-positive apoptotic cells. Co-administration of the AMPK inhibitor compound C completely abolished the inhibitory effects of metformin on caspase cascade activation, significantly reversed the beneficial effects of metformin on histopathological abnormalities and hepatocytes apoptosis, and partially abolished the suppressive effects of metformin on plasma ALT elevation. These data indicated that metformin effectively alleviated TNF-alpha/D-Gal-induced apoptotic liver injury and these beneficial effects were at least partially mediated by AMPK. PMID- 26265046 TI - Regulation of MALAT1 expression by TDP43 controls the migration and invasion of non-small cell lung cancer cells in vitro. AB - MALAT1 is a non-coding RNA overexpressed in non-small cell lung cancer (NSCLC). TDP-43 is a ubiquitously expressed, MALAT1-binding protein implicated in cancer development. We hypothesized that MALAT1 expression level is regulated in lung cancer by TDP-43. We analyzed their functions in cultured NSCLC cells. Downregulation of MALAT1 or TDP-43 expression by siRNA not only markedly suppressed NSCLC cell growth, as measured by the MTT assay in vitro cultured NSCLC cells (P < 0.05), but also noticeably impaired the migration and invasion of NSCLC cells, as analyzed by the migration and invasion assay. We also confirm that TDP-43 directly bound to MALAT1 RNA by a RNA immunoprecipitation (RIP) assay and by luciferase reporter activity assay. In a RT-PCR assay, silencing TDP-43 expression effectively decreased MALAT1 RNA transcript level. In contrast, TDP-43 overexpression markedly increased MALAT1 transcript level. In summary, these findings demonstrated that MALAT1 expression by regulation of TDP-43 controls cellular growth, migration, and invasion of NSCLCs. PMID- 26265047 TI - Cellular activity of Wharton's Jelly-derived mesenchymal stem cells on electrospun fibrous and solvent-cast film scaffolds. AB - It was shown that topography and surface chemistry of materials influence cell behaviors. In this study, the effects of chemistry and topography of scaffold surface on adhesion, proliferation and differentiation of Wharton's Jelly mesenchymal (WJMSCs) stem cells into motor neurons were investigated. WJMSCs were cultivated in an neurogenic inductive medium on the surface of modified and unmodified polycaprolactone (PCL) electrospun fibrous and solvent-cast film scaffolds. All the scaffolds were characterized according to their ability to support cell attachment and viability by SEM and MTT assay. The expression of motor neuron-specific markers was assayed by real-time PCR after 15days post induction. Results showed that attachment, proliferation and differentiation of WJMSCs into motor neuron-like cells on the nanotopographic surface was higher than that of the cells on the solvent-cast scaffolds. In addition, regardless of their topography, WJMSCs cultured on collagen-coated PCL nanofibrous showed results similar to collagen-coated PCL films. Results suggested that surface chemistry has more impact on WJMSCs behaviour rather than topography. In conclusion, collagen-coated electrospun PCL have potential for being used in neural tissue engineering because of its bioactive and three-dimensional structure which enhance viability and differentiation of WJMSCs. PMID- 26265049 TI - Resection of a juvenile nasoangiofibroma by Le Fort I osteotomy: Experience with 40 cases. AB - PURPOSE: The aim of this study was to determine the rate of success and complications of juvenile nasoangiofibroma resection by Le Fort I osteotomy. MATERIAL AND METHODS: Data were obtained from the medical records of 40 patients with a diagnosis of juvenile nasoangiofibroma confirmed by anatomopathological examination. All tumors were resected by Le Fort I osteotomy between 1983 and 2010. The data obtained were gender, age, symptoms, sites of invasion, preoperative embolization, routes of surgical access, duration of surgery, complications, need for transfusion, relapses, and follow-up time. RESULTS: All patients were male, ranging in age from 7 to 27 years. The most common symptom was nasal obstruction, and central nervous system (CNS) invasion was present in 27.5% of cases. Craniotomy was associated with Le Fort I osteotomy in only one case. The mean duration of surgery was 216 min. Complications occurred in 15% of cases, with intraoperative bleeding being the most frequent one. Relapses occurred in 5% of cases. The mean follow-up was 48.8 months. CONCLUSION: Exclusively surgical treatment by Le Fort I access proved to be a safe and effective method for the treatment of nasoangiofibromas, permitting the removal of tumors even in patients with extension to the CNS, with a low rate of complications and relapses. PMID- 26265048 TI - Targeting lysyl oxidase for molecular imaging in breast cancer. AB - INTRODUCTION: Lysyl oxidase (LOX; ExPASy ENZYME entry: EC 1.4.3.13) and members of the LOX-like family, LOXL1-LOXL4, are copper-dependent enzymes that can modify proteins of the extracellular matrix. Expression of LOX is elevated in many human cancers, including breast cancer. LOX expression correlates with the level of tissue hypoxia, and it is known to play a critical role in breast cancer metastasis. The goal of the present study was to target LOX with (1) molecular probe fluorescent labeling to visualize LOX in vitro and (2) a radiolabeled peptide to target LOX in vivo in three different preclinical models of breast cancer. METHODS: Gene expression of all five members of the LOX family was analyzed at the transcript level via microarray analysis using tissue biopsy samples from 176 patients with breast cancer. An oligopeptide sequence (GGGDPKGGGGG) was selected as a substrate-based, LOX-targeting structure. The peptide was labeled with fluorescein isothiocyanate (FITC) for confocal microscopy experiments with the murine breast cancer cell line EMT-6. In vivo molecular imaging experiments were performed using a C-terminal amidated peptide, GGGDPKGGGGG, labeled with a short-lived positron emitter, fluorine-18 ((18)F), for positron emission tomography (PET) in three different breast cancer models: EMT6, MCF-7 and MDA-MB-231. The PET experiments were carried out in the presence or absence of beta-aminopropionitrile (BAPN), an irreversible inhibitor of LOX. RESULTS: Immunostaining experiments using a LOX-specific antibody on EMT-6 cells cultured under hypoxic conditions confirmed the elevation of LOX expression in these cells. An FITC-labeled oligopeptide, FITC-Ava-GGGDPKGGGGG-NH2, was found to be localized in different cellular compartments under these conditions. After injection of [(18)F]fluorobenzoate-GGGDPKGGGGG-NH2, radioactivity uptake was visible in all three breast cancer models in vivo. Tumor uptake was reduced by predosing the animals with 2 mg of BAPN 4 h or 24 h before injection of the radiotracer. CONCLUSIONS: The present data support further investigation into the development of LOX-binding radiolabeled peptides as molecular probes for molecular imaging of LOX expression in cancer. PMID- 26265050 TI - Non-actual motion: phenomenological analysis and linguistic evidence. AB - Sentences with motion verbs describing static situations have been seen as evidence that language and cognition are geared toward dynamism and change (Talmy in Toward a cognitive semantics, MIT Press, Cambridge, 2000; Langacker in Concept, image, and symbol: the cognitive basis of grammar, Mouton de Gruyter, Berlin and New York, 1990). Different concepts have been used in the literature, e.g., fictive motion, subjective motion and abstract motion to denote this. Based on phenomenological analysis, we reinterpret such concepts as reflecting different motivations for the use of such constructions (Blomberg and Zlatev in Phenom Cogn Sci 13(3):395-418, 2014). To highlight the multifaceted character of the phenomenon, we propose the concept non-actual motion (NAM), which we argue is more compatible with the situated cognition approach than explanations such as "mental simulation" (e.g., Matlock in Studies in linguistic motivation, Mouton de Gruyter, Berlin, 2004). We investigate the expression of NAM by means of a picture-based elicitation task with speakers of Swedish, French and Thai. Pictures represented figures that either afford human motion or not (+/-afford); crossed with this, the figure extended either across the picture from a third person perspective (3 pp) or from a first-person perspective (1 pp). All picture types elicited NAM-sentences with the combination [+afford, 1 pp] producing most NAM-sentences in all three languages. NAM-descriptions also conformed to language specific patterns for the expression of actual motion. We conclude that NAM shows interaction between pre-linguistic motivations and language-specific conventions. PMID- 26265051 TI - Patients' perceptions on the impact of coffee consumption in inflammatory bowel disease: friend or foe?--a patient survey. AB - BACKGROUND: Environmental factors are an integral component in the pathogenesis of inflammatory bowel disease (IBD). There is an increasing interest in nutritive components. While the potential disease-modifying role of coffee has been intensively investigated in a variety of gastrointestinal diseases, the data on the potential impact on IBD is very limited. We aimed to determine the patients' perspective on coffee consumption in IBD. METHODS: We conducted a questionnaire among IBD patients in Switzerland, assessing key questions regarding coffee consumption. Descriptive statistics including chi square testing were used for analysis of questionnaire data. RESULTS: Among a total of 442 patients 73% regularly consume coffee. 96% of patients attributing a positive and 91% of patients attributing no impact of coffee intake on IBD regularly drink coffee and surprisingly even 49% of those patients that assign a negative impact on disease symptoms. Among those patients refraining from regular coffee intake 62% are convinced that coffee adversely influences intestinal symptoms, significantly more in Crohn's disease (CD) than in ulcerative colitis (UC) (76% vs. 44%, p = 0.002). In total, 38% of all study subjects suppose that coffee has an effect on their symptoms of disease, significantly more in CD (54%) compared to UC patients (22%, p < 0.001). Moreover, while 45% of CD patients feel that coffee has a detrimental influence, only 20% of UC patients share this impression (p < 0.001). CONCLUSION: Two thirds of IBD patients regularly consume coffee. More than twice as many CD compared to UC patients attribute a symptom-modifying effect of coffee consumption, the majority a detrimental one. However, this negative perception does not result in abstinence from coffee consumption. PMID- 26265052 TI - Antioxidant peroxiredoxin 6 protein rescues toxicity due to oxidative stress and cellular hypoxia in vitro, and attenuates prion-related pathology in vivo. AB - Protein misfolding, mitochondrial dysfunction and oxidative stress are common pathomechanisms that underlie neurodegenerative diseases. In prion disease, central to these processes is the post-translational transformation of cellular prion protein (PrP(c)) to the aberrant conformationally altered isoform; PrP(Sc). This can trigger oxidative reactions and impair mitochondrial function by increasing levels of peroxynitrite, causing damage through formation of hydroxyl radicals or via nitration of tyrosine residues on proteins. The 6 member Peroxiredoxin (Prdx) family of redox proteins are thought to be critical protectors against oxidative stress via reduction of H2O2, hydroperoxides and peroxynitrite. In our in vitro studies cellular metabolism of SK-N-SH human neuroblastoma cells was significantly decreased in the presence of H2O2 (oxidative stressor) or CoCl2 (cellular hypoxia), but was rescued by treatment with exogenous Prdx6, suggesting that its protective action is in part mediated through a direct action. We also show that CoCl2-induced apoptosis was significantly decreased by treatment with exogenous Prdx6. We proposed a redox regulator role for Prdx6 in regulating and maintaining cellular homeostasis via its ability to control ROS levels that could otherwise accelerate the emergence of prion-related neuropathology. To confirm this, we established prion disease in mice with and without astrocyte-specific antioxidant protein Prdx6, and demonstrated that expression of Prdx6 protein in Prdx6 Tg ME7-animals reduced severity of the behavioural deficit, decreased neuropathology and increased survival time compared to Prdx6 KO ME7-animals. We conclude that antioxidant Prdx6 attenuates prion-related neuropathology, and propose that augmentation of endogenous Prdx6 protein represents an attractive adjunct therapeutic approach for neurodegenerative diseases. PMID- 26265055 TI - HLA alleles and haplotypes in Burmese (Myanmarese) and Karen in Thailand. AB - This is the first report on human leukocyte antigen (HLA) allele and haplotype frequencies at three class I loci and two class II loci in unrelated healthy individuals from two ethnic groups, 170 Burmese and 200 Karen, originally from Burma (Myanmar), but sampled while residing in Thailand. Overall, the HLA allele and haplotype frequencies detected by polymerase chain reaction sequence-specific primer (PCR-SSP) at five loci (A, B, C, DRB1 and DRQB1) at low resolution showed distinct differences between the Burmese and Karen. In Burmese, five HLA-B*15 haplotypes with different HLA-A and HLA-DR/DQ combinations were detected with three of these not previously reported in other Asian populations. The data are important in the fields of anthropology, transplantation and disease-association studies. PMID- 26265053 TI - Inducible nitric oxide synthase mediates DNA double strand breaks in Human T-Cell Leukemia Virus Type 1-induced leukemia/lymphoma. AB - BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive and fatal malignancy of CD4(+) T-lymphocytes infected by the Human T-Cell Virus Type 1 (HTLV-1). The molecular mechanisms of transformation in ATLL have not been fully elucidated. However, genomic instability and cumulative DNA damage during the long period of latency is believed to be essential for HTLV-1 induced leukemogenesis. In addition, constitutive activation of the NF-kappaB pathway was found to be a critical determinant for transformation. Whether a connection exists between NF-kappaB activation and accumulation of DNA damage is not clear. We recently found that the HTLV-1 viral oncoprotein, Tax, the activator of the NF kappaB pathway, induces DNA double strand breaks (DSBs). RESULTS: Here, we investigated whether any of the NF-kappaB target genes are critical in inducing DSBs. Of note, we found that inducible nitric oxide synthase (iNOS) that catalyzes the production of nitric oxide (NO) in macrophages, neutrophils and T cells is over expressed in HTLV-1 infected and Tax-expressing cells. Interestingly, we show that in HTLV-1 infected cells, iNOS expression is Tax dependent and specifically requires the activation of the classical NF-kappaB and JAK/STAT pathways. A dramatic reduction of DSBs was observed when NO production was inhibited, indicating that Tax induces DSBs through the activation of NO synthesis. CONCLUSIONS: Determination of the impact of NO on HTLV-1-induced leukemogenesis opens a new area for treatment or prevention of ATLL and perhaps other cancers in which NO is produced. PMID- 26265056 TI - A novel HLA-B allele, HLA-B*58:66. AB - HLA-B*58:66 differs from B*58:01:01 by a single-synonymous nucleotide at position 685 where G -> T (codon 205 GCC -> TCC, Ala>Ser). PMID- 26265057 TI - Nomenclature for factors of the HLA system, update April 2015. PMID- 26265058 TI - Nomenclature for factors of the HLA system, update May 2015. PMID- 26265059 TI - Nomenclature for factors of the HLA system, update June 2015. PMID- 26265061 TI - Investigating the role of Pluronic-g-Cationic polyelectrolyte as functional stabilizer for nanocrystals: Impact on Paclitaxel oral bioavailability and tumor growth. AB - Paclitaxel (PTX) is a potent anticancer drug which suffers limitations of extremely low oral bioavailability due to low solubility, rapid metabolism and efflux by P-gp transporters. The main objective of this study was to overcome the limitation of PTX by designing delivery systems that can enhance the absorption using multiple pathways. A novel Pluronic-grafted chitosan (Pl-g-CH) copolymer was developed and employed as a functional stabilizer for nanocrystals (NCs) and hypothesized that it would improve PTX absorption by several mechanisms and pathways. Pl-g-CH was synthesized and characterized using (1)H NMR and then used as a stabilizer during nanocrystal development. To establish our proof of concept the optimized formulation having a particle size 192.7 +/- 9.2 nm and zeta potential (+) 38.8 +/- 3.12 mV was studied extensively on in vitro Caco-2 model. It was observed that nanocrystals rendered higher PTX accumulation inside the cell than TaxolTM. P-gp inhibitory potential of Pl-g-CH was proved by flow cytometry and fluorescence microscopy where the much enhanced fluorescence intensity of Rhodamine 123 (Rho-123, P-gp substrate) was observed in the presence of Pl-g-CH. In addition, a significant decrease in Trans Epithelial Electrical Resistance (TEER) of Caco-2 cell monolayers was observed with nanocrystals as well as with TaxolTM (in the presence of free Pl-g-CH compared to only TaxolTM). This supports the role of the stabilizer in reversible opening of tight junctions between cells which can allow paracellular transport of drug. The in vivo results were in complete corroboration with in vitro results. Nanocrystals resulted in much enhanced absorption with 12.6-fold improvement in relative bioavailability to that of TaxolTM. Concomitantly efficacy data in B16 F10 murine melanoma model also showed a significant reduction in tumor growth with nanocrystals compared to TaxolTM and control. Based on the results it can be suggested that nanocrystals with functional stabilizers can be a promising approach for the oral delivery of anticancer drugs which are P-gp substrates STATEMENT OF SIGNIFICANCE: Nanocrystals are currently one of the most explored novel drug delivery systems especially for oral delivery of drugs because of ease in synthesis and high drug loading. But their use is still limited for oral delivery of anticancer drugs which are P-gp substrates. This particular study aims at widening the scope of nanocrystals by using a functional stabilizer which participates in enhancing the oral absorption of anticancer drugs and controlling the tumor growth. PMID- 26265060 TI - Intramyocardial injection of hydrogel with high interstitial spread does not impact action potential propagation. AB - Injectable biomaterials have been evaluated as potential new therapies for myocardial infarction (MI) and heart failure. These materials have improved left ventricular (LV) geometry and ejection fraction, yet there remain concerns that biomaterial injection may create a substrate for arrhythmia. Since studies of this risk are lacking, we utilized optical mapping to assess the effects of biomaterial injection and interstitial spread on cardiac electrophysiology. Healthy and infarcted rat hearts were injected with a model poly(ethylene glycol) hydrogel with varying degrees of interstitial spread. Activation maps demonstrated delayed propagation of action potentials across the LV epicardium in the hydrogel-injected group when compared to saline and no-injection groups. However, the degree of the electrophysiological changes depended on the spread characteristics of the hydrogel, such that hearts injected with highly spread hydrogels showed no conduction abnormalities. Conversely, the results of this study indicate that injection of a hydrogel exhibiting minimal interstitial spread may create a substrate for arrhythmia shortly after injection by causing LV activation delays and reducing gap junction density at the site of injection. Thus, this work establishes site of delivery and interstitial spread characteristics as important factors in the future design and use of biomaterial therapies for MI treatment. STATEMENT OF SIGNIFICANCE: Biomaterials for treating myocardial infarction have become an increasingly popular area of research. Within the past few years, this work has transitioned to some large animals models, and Phase I & II clinical trials. While these materials have preserved/improved cardiac function the effect of these materials on arrhythmogenesis, which is of considerable concern when injecting anything into the heart, has yet to be understood. Our manuscript is therefore a first of its kind in that it directly examines the potential of an injectable material to create a substrate for arrhythmias. This work suggests that site of delivery and distribution in the tissue are important criteria in the design and development of future biomaterial therapies for myocardial infarction treatment. PMID- 26265063 TI - Antibiotic therapy in fully impacted lower third molar surgery: randomized three arm, double-blind, controlled trial. AB - PURPOSE: The aim of this study was to evaluate the efficacy of three drug protocols in patients undergoing extraction of fully impacted lower third molars. METHODS: Eighty surgeries were performed on healthy patients using three randomized double-blind drug protocols: group 1 (G1), amoxicillin (1 g) 1 h before surgery + 500 mg 8/8 h for 7 days; group 2 (G2), 1-g amoxicillin 1 h before surgery plus placebo, with identical appearance to G1, 8/8 h for 7 days; and group 3 (G3), placebo 1 h before surgery and 500 mg 8/8 h for 7 days. The primary outcome criterion was mouth opening, and the secondary outcome criteria were facial edema and pain. Signals as body temperature, lymphadenopathy, and dysphagia characterize the sample. Evaluation was performed at baseline and on the 4th and 7th postoperative days by the same researcher. RESULTS: There was no difference among groups with respect to any of the parameters evaluated (p > 0.05). CONCLUSION: Under these experimental conditions, there is no advantage in the administration of antibiotics in healthy patients undergoing extraction of fully impacted lower third molars with a controlled aseptic chain. PMID- 26265062 TI - Bone mineral density after implantation of a femoral neck hip prosthesis--a prospective 5 year follow-up. AB - BACKGROUND: Bone resorption in the proximal femur due to stress shielding has been observed in a number of conventional cementless implants used in total hip arthroplasty. Short femoral-neck implants are claiming less interference with the biomechanics of the proximal femur. The goal of this study was to prospectively investigate the in vivo changes of bone-mineral density as a parameter of bone remodeling around a short, femoral neck prosthesis over the first 5 years following implantation. The secondary goal was to report on its clinical outcome. METHODS: We are reporting on the changes of bone mineral density of the proximal femur and the clinical outcome up to five years after implantation of a short femoral neck prosthesis. Bone mineral density was determined using dual energy x ray absorptiometry, performed 10 days, three, 12 and 60 months after surgery. 20 patients with a mean age of 47 years (range 17 to 65) were clinically assessed using the Harris Hip Score. The WOMAC was used as a patient-relevant outcome measure. RESULTS: In contrast to conventional implants DEXA-scans overall revealed a slight increase of bone mineral density in the proximal femur in the 12 months following the implantation. The Harris Hip Score improved from an average preoperative score of 46 to a postoperative score at 12 months of 91 points and 95 points at 60 months, the global WOMAC index from 5.3 preoperatively to 0.8 at 12 months and 0.6 at 60 months postoperatively. CONCLUSION: At 60 months after implantation of a short femoral neck prosthesis, all regions except one (region of interest #5) showed no significant changes in BMD compared to baseline measurements at 10 days which is less to the changes in bone mineral density seen in conventional implants. PMID- 26265064 TI - Sinus grafting and simultaneous removal of large antral pseudocysts of the maxillary sinus with a micro-invasive intraoral access. AB - Large antral pseudocysts of the maxillary sinus (APCs) may hamper the elevation of the Schneiderian membrane during sinus grafting and may impair osteo-meatal complex patency after sinus augmentation. Therefore, these should be removed prior to or at the time of sinus grafting. This study presents a new technique that combines enucleation of large APCs during sinus grafting via a lateral approach with preservation of the Schneiderian membrane periosteal layer. Twelve patients underwent a sinus graft via lateral approach during the years 2004-2012. Simultaneous APC removal was achieved through a small additional bony access, preserving the integrity of the periosteal layer of the Schneiderian membrane. Nineteen implants were inserted at the time of sinus augmentation or during a second stage. Prosthetic rehabilitation was started at 4-6 months after implant placement. No patient developed surgical complications or APC recurrence. The survival rate of implants and related prostheses was 100% over a mean follow-up of 50 months (range 12-96 months) after completion of the prosthetic restorations. This technique may represent an effective procedure to achieve APC removal at the time of sinus grafting, preserving the integrity of the Schneiderian membrane periosteal layer. PMID- 26265065 TI - Comparison of virtual and titanium clip marking of tumour resection margins for improved radiation planning in head and neck cancer surgery. AB - Communication between the surgeon and the radiation oncologist is improved with the use of virtual models of the final tumour resection, combining three dimensional imaging and conventional clip marking with computer-aided navigation. This investigation was designed to determine the deviation of virtual marking procedures compared to conventional marking by titanium ligature clips in oral cancer with different localizations. Seventeen patients with surgically placed clips and virtual landmarks on the resection margin after complete tumour ablation were evaluated. To determine whether the virtual landmarks remain predictive of the resection margin, the deviation of the virtual points from their corresponding clips was analyzed by measuring the distance between their centres of gravity. In total, 189 clips were evaluated. Metric analyses of the deviation between the virtual points and clips showed a deviation of 2.3 +/- 0.6mm for tumours with a maxilla localization, 7.2 +/- 2.5mm for tumours with a mandible localization, and 12.6 +/- 3.8mm for tumours with a tongue localization. A significant statistical relationship was demonstrated in the virtual point-clip deviation as a function of tumour localization. Virtual marking of maxillary tumour resection margins allows accurate definition of the former tumour bed and could lead to novel adjuvant treatment strategies. PMID- 26265066 TI - Who tests whom? A comprehensive overview of Chlamydia trachomatis test practices in a Dutch region among different STI care providers for urogenital, anorectal and oropharyngeal sites in young people: a cross-sectional study. AB - OBJECTIVES: To evaluate and compare Chlamydia trachomatis (CT) diagnostic test practices of different sexually transmitted infection (STI) care providers in 16 29 year olds from one defined geographic Dutch region (280,000 inhabitants). Both number and proportion of positive CT tests (ie, test positivity) were assessed, and factors associated with these outcomes. METHODS: Data on laboratory testing and diagnosis of urogenital, anorectal and oropharyngeal CT between 2006 and 2010 were retrieved from general practitioners (GPs), gynaecologists, an STI clinic and a population-based chlamydia screening programme. Multivariable regression analyses explored associations between age, sex, test year, socio-economic status (SES) and STI care provider and the outcomes being the number of tests and test positivity. RESULTS: Overall, 22,831 tests were performed (1868 positive; 8.2%). Extragenital (ie, anorectal and oropharyngeal) tests accounted for 4% of all tests (7.5% positive) and were almost exclusively (99%) performed by the STI clinic. STI clinics tested most men (37.2% of all tested men), whereas GPs tested most women (29.9% of all tested women). GPs and STI clinics accounted for 73.3% (1326/1808) of urogenital CT diagnoses. In women, the number of tests increased with age, whereas test positivity decreased for all STI care providers. Lower SES was associated with higher test positivity in GP and gynaecology patients. CONCLUSIONS: STI clinics performed most CT tests in men, whereas GPs performed most CT tests in women. GPs and STI clinics accounted for the majority of positives. Extragenital CT testing is rarely performed outside the STI clinic and needs to be promoted, especially in men who have sex with men. PMID- 26265067 TI - Global Analysis of Protein Expression and Phosphorylation Levels in Nicotine Treated Pancreatic Stellate Cells. AB - Smoking is a risk factor in pancreatic disease; however, the biochemical mechanisms correlating smoking with pancreatic dysfunction remain poorly understood. Strategies using multiplexed isobaric tag-based mass spectrometry facilitate the study of drug-induced perturbations on biological systems. Here, we present the first large-scale analysis of the proteomic and phosphoproteomic alterations in pancreatic stellate cells following treatment with two nicotinic acetylcholine receptor (nAChR) ligands: nicotine and alpha-bungarotoxin. We treated cells with nicotine or alpha-bungarotoxin for 12 h in triplicate and compared alterations in protein expression and phosphorylation levels to mock treated cells using a tandem mass tag (TMT9plex)-based approach. Over 8100 proteins were quantified across all nine samples, of which 46 were altered in abundance upon treatment with nicotine. Proteins with increased abundance included those associated with neurons, defense mechanisms, indicators of pancreatic disease, and lysosomal proteins. In addition, we measured differences for ~16 000 phosphorylation sites across all nine samples using a titanium dioxide-based strategy, of which 132 sites were altered with nicotine and 451 with alpha-bungarotoxin treatment. Many altered phosphorylation sites were involved in nuclear function and transcriptional events. This study supports the development of future targeted investigations to establish a better understanding for the role of nicotine and associated receptors in pancreatic disease. PMID- 26265068 TI - Neopterin predicts cardiac dysfunction following cardiac surgery. AB - OBJECTIVES: Oxidative stress following ischaemia and reperfusion, as well as inflammation, are thought to be important for the development of cardiac dysfunction after cardiac surgery. Our main objective was to investigate whether the inflammatory biomarkers C-reactive protein (CRP), lactoferrin, neopterin and the terminal complement complex (TCC) were associated with cardiac dysfunction after cardiac surgery. Another objective was to assess whether the biomarkers could improve prediction of postoperative cardiac dysfunction compared with clinical variables only. METHODS: Blood samples and clinical data from 1018 consecutive patients undergoing cardiac surgery from 1 April 2008 to 19 April 2010 at St. Olavs University Hospital, Trondheim, Norway, were collected prospectively. The end-point was postoperative cardiac dysfunction, defined as the need for more than one inotropic agent or an intra-aortic balloon pump occurring after the operation and until the patient was discharged from the department. CRP, lactoferrin, neopterin and TCC were analysed in plasma, and we used logistic regression to evaluate the association of the biomarkers with postoperative cardiac dysfunction. We adjusted for the following clinical variables previously associated with postoperative cardiac dysfunction: urgent operation, operation type, previous cardiac surgery, chronic heart failure, pulmonary hypertension, previous myocardial infarction and haemoglobin. The likelihood ratio test, the integrated discrimination improvement and receiver operating characteristic (ROC) curves were used to assess whether the biomarkers could improve prediction of postoperative cardiac dysfunction compared with clinical variables alone. RESULTS: Neopterin was the only biomarker significantly associated with postoperative cardiac dysfunction (odds ratio 2.73, 95% confidence interval 1.65-4.51) after adjustment for clinical variables. Neopterin improved risk prediction of cardiac dysfunction following heart surgery compared with clinical variables alone according to the likelihood ratio test (P < 0.0001) and the integrated discrimination improvement (P = 0.02), particularly for patients with intermediate risks. CONCLUSIONS: Neopterin was associated with cardiac dysfunction following cardiac surgery, and improved the accuracy of risk prediction of postoperative cardiac dysfunction. At present, we do not suggest that neopterin should be measured routinely before heart surgery, but our findings support the hypothesis of the role of oxidative stress and inflammation in development of cardiac dysfunction following heart surgery. PMID- 26265069 TI - Safety and efficacy of glucose-insulin-potassium treatment in coronary artery bypass graft surgery and percutaneous coronary intervention. AB - The purpose of this meta-analysis was to evaluate protective effects of glucose insulin-potassium (GIK) on outcomes after coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). We systematically searched Medline/Pubmed, Elsevier, Embase, Web of Knowledge and Google Scholar. A total of 1206 studies were retrieved during the extensive literature search of all major databases; however, 38 trials reporting the end-point of interest were selected. We performed a pooled analysis of outcomes following PCI: incidence of cardiac arrest [odds ratio (OR) of 0.91; 95% confidence interval (CI): 0.76-1.09; P = 0.3], stroke (OR of 1.71; 95% CI: 0.37-1.37; P = 0.3), cardiogenic shock (OR of 1.02; 95% CI: 0.92-1.14; P = 0.6), reinfarction (OR of 0.95; 95% CI: 0.81-1.14; P = 0.5) and mortality (OR of 1.04; 95% CI: 0.96-1.13; P = 0.3); and following CABG: incidence of atrial fibrillation (OR of 0.86; 95% CI: 0.70-1.05; P = 0.1), incidence of ventricular fibrillation (OR of 0.83; 95% CI: 0.62-1.13; P = 0.2), reinfarction (OR of 0.97; 95% CI: 0.74-1.27; P = 0.8), infection (OR of 1.04; 95% CI: 0.67-1.62; P = 0.8), length of intensive care unit stay (LIS) [standard mean differences (SMD) of -0.27; 95% CI: -0.40 to -0.14; P = 0.000], length of hospital stay (LHS) (SMD of -0.035; 95% CI: -0.12 to -0.05; P = 0.4) and mortality (OR of 0.72; 95% CI: 0.41-1.26; P = 0.2). Our results showed that GIK did not have considerable cardioprotective effects. However, patients undergoing CABG seem to be better responders to GIK therapy compared with patients undergoing PCI. Furthermore, in contrast to CABG, GIK therapy in patients undergoing PCI might be associated with more complications rather than protective effects. PMID- 26265070 TI - Transcatheter aortic valve implantation in a patient with bicuspid aortic stenosis and a borderline-sized annulus. AB - Bicuspid aortic valve (BAV) is currently considered an exclusion criterion for transcatheter aortic valve implantation (TAVI). The risk of adverse aortic events such as incomplete sealing, severe paravalvular regurgitation or dislocation due to elliptic shape and asymmetric calcifications in annulus are higher in TAVI. In this case report, we detailed a case of successful trans-femoral TAVI in a 51 year old male with BAV and its management without in-hospital and 30-day complications. The challenge in this case was the patient's anatomy with a 27-mm annulus for balloon expandable device. The applied strategy was balloon sizing and overdilating the 29-mm stented valve with additional volume that obviated re ballooning. Trans-femoral TAVI was performed uneventfully under fluoroscopic and transoesophageal echocardiography guidance. A multidetector computed tomography (MDCT) evaluation at 1 month did not show device dislodgement or any other complications. Evidence for evaluation post-TAVI is not sufficient in BAV. We believe patients with BAV should undergo a comprehensive assessment after TAVI including MDCT evaluation. PMID- 26265071 TI - Apical closure device for transapical valve procedures. AB - OBJECTIVES: Transapical transcatheter valve procedures are performed through a left minithoracotomy and require apical sutures to seal the apical access site. The use of large-calibre devices compromises any attempt to fully perform the procedure with a thoracoscopic approach or percutaneously. We report our preliminary experience in animals with a new sutureless self-expandable apical occluder, engineered to perform transapical access site closure in a minimally invasive setting with large-size introducer sheaths. METHODS: The apical occluder with extendable waist was implanted in six young pigs during an acute animal study. Under general anaesthesia, animals (mean weight: 62 +/- 8 kg) received full heparinization (heparin: 100 UI/kg; activated clotting time above 250 s). Through a median sternotomy, a 21-Fr CertitudeTM introducer sheath (outer diameter: 25 Fr) was placed over the wire into the cardiac apex. The delivery catheter carrying the constrained apical plug was inserted into the sheath and deployed under fluoroscopic control, whereas the CertitudeTM was retrieved. After protamine infusion, we observed and recorded the 1-h bleeding with standard haemodynamic parameters. Animals were sacrificed, and hearts analysed. RESULTS: Six apical closure devices were successfully introduced and deployed in six pig hearts through large-size apical sheaths at first attempt. In all animals, the plugs guaranteed immediate apical sealing and traces of blood were collected in the pericardium during the 1-h observational period (mean of 16 +/- 3.4 ml of blood loss per animal). Haemodynamic parameters remained stable during the entire study period and no plug dislodgement was detected with normal systemic blood pressure (mean arterial mean blood pressure: 65 +/- 7 mmHg). Post-mortem analysis confirmed the full deployment and good fixation of all plugs, without macroscopic damages to the surrounding myocardium. CONCLUSIONS: This sutureless self expandable apical occluder is a simple device capable of sealing large-size apical access sites (20-35 Fr) in an acute animal study. This approach is a step further towards less invasive transapical valve procedures in the clinical setting, and further animal tests will be performed to confirm the long-term efficacy and safety of this device. PMID- 26265072 TI - Deletion of the tyrosine phosphatase Shp2 in Sertoli cells causes infertility in mice. AB - The male's ability to reproduce is completely dependent on Sertoli cells. However, the mechanisms governing the functional integrity of Sertoli cells have remained largely unexplored. Here, we demonstrate that deletion of Shp2 in Sertoli cells results in infertility in mice. In Shp2 knockout mice (SCSKO), a normal population of Sertoli cells was observed, but the blood-testis barrier (BTB) was not formed. Shp2 ablation initiated the untimely and excessive differentiation of spermatogonial stem cells (SSCs) by disturbing the expression of paracrine factors. As a consequence, the process of spermatogenesis was disrupted, and the germ cells were depleted. Furthermore, Shp2 deletion impaired the cell junctions of the primary Sertoli cells and failed to support the clonal formation of SSCs co-cultured with SCSKO Sertoli cells. As expected, Shp2 restoration largely restores the cell junctions of the primary Sertoli cells and the clonal formation of SSCs. To identify the underlying mechanism, we further demonstrated that the absence of Shp2 suppressed Erk phosphorylation, and thus, the expression of follicle-stimulating hormone (FSH)- and testosterone-induced target genes. These results collectively suggest that Shp2 is a critical signaling protein that is required to maintain Sertoli cell function and could serve as a novel target for male infertility therapies. PMID- 26265074 TI - Atrial septal defect and training-induced changes in loading conditions: clinical management and implications for competitive athletes. AB - Atrial septal defect (ASD) is the most common congenital heart disease in adults. When right heart dilation occurs, prompt closure should be considered. In the athletic population, however, the management of ASD can be challenging. Indeed, while the training-induced haemodynamic effects on the right heart of an athlete with open ASD are not well known, possible device-related consequences may occur after percutaneous closure. We report the case of a competitive athlete with secundum ASD in which changes in the training regime significantly affected the right heart. Prompt normalisation of right ventricular size and of pulmonary artery pressures was demonstrated 2 months after percutaneous ASD closure. PMID- 26265073 TI - For whom the cells pull: Hydrogel and micropost devices for measuring traction forces. AB - While performing several functions, adherent cells deform their surrounding substrate via stable adhesions that connect the intracellular cytoskeleton to the extracellular matrix. The traction forces that deform the substrate are studied in mechanotrasduction because they are affected by the mechanics of the extracellular milieu. We review the development and application of two methods widely used to measure traction forces generated by cells on 2D substrates: (i) traction force microscopy with polyacrylamide hydrogels and (ii) calculation of traction forces with arrays of deformable microposts. Measuring forces with these methods relies on measuring substrate displacements and converting them into forces. We describe approaches to determine force from displacements and elaborate on the necessary experimental conditions for this type of analysis. We emphasize device fabrication, mechanical calibration of substrates and covalent attachment of extracellular matrix proteins to substrates as key features in the design of experiments to measure cell traction forces with polyacrylamide hydrogels or microposts. We also report the challenges and achievements in integrating these methods with platforms for the mechanical stimulation of adherent cells. The approaches described here will enable new studies to understand cell mechanical outputs as a function of mechanical inputs and advance the understanding of mechanotransduction mechanisms. PMID- 26265075 TI - Effects of short term elastic resistance training on muscle mass and strength in untrained older adults: a randomized clinical trial. AB - BACKGROUND: The current recommendations on resistance training involving older adults have reported an improvement of body composition variables. Despite this, there is a lack of knowledge on how elastic resistance training (ERT) affects the muscle mass in older adults population. The purpose of this study was to determine the effects of a short-term ERT on muscle mass of health and untrained older adults. METHODS: Forty older adults were randomized into two groups of 20 individuals each: Control Group (CG = 66.2 +/- 6.6 years) and Training Group (TG = 69.1 +/- 6.3 years). TG underwent an ERT twice a week during 8 weeks and control group did not receive any specific intervention. The primary outcome was the upper and lower limbs muscle mass, measured by Dual-energy x-ray absorptiometry. The secondary outcomes were knee isokinetic peak torque (PT) at 60 degrees /s and 120 degrees /s speeds and isometric handgrip strength. A 2*2 mixed model (group [TG and CG] * time [pre and post]) analysis of variance (ANOVA) was applied to determine the effect on primary and secondary outcomes. RESULTS: The results of the ANOVA showed no significant effects in group x time interaction for (1) upper limbs fat free mass (F [1.38] = 1.80, p = 0.19, effect size [ES] = 0.1) and for (2) lower limbs fat free mass (F [1.38] = 0.03, p = 0.88, ES = 0.02). Regarding muscle strength, the ANOVA showed no significant effects in group x time interaction for (3) PT at 60 degrees /s (F [1.38] = 0.33, p = 0.56, ES = 3.0), for (4) PT at 120 degrees /s (F [1.38] = 0.80, p = 0.38, ES = 4.1) and for handgrip strength (F [1.38] = 0.65, p = 0.42-value, ES = 0.9). Analysis of PT in TG showed a significant change of 4.5%, but only at 120 degrees /s (p = 0.01) when comparing pre and post-training (time interaction). CONCLUSIONS: Eight weeks of ERT did not show significant changes in muscle mass and strength of untrained older adults. TRIAL REGISTRATION: NCT02253615 (09/25/14). PMID- 26265076 TI - Obituary: Herbert Lochs - A charismatic speaker. PMID- 26265077 TI - Frailty: a tale of two concepts. AB - Frailty is increasingly relevant for clinicians to improve care for vulnerable older adults. Prominent frailty measures include the frailty phenotype and the frailty index. The frailty phenotype is grounded in a theoretical construct hypothesized to have an underlying biological basis. The frailty index describes frailty as a nonspecific age-associated vulnerability, reflected in an accumulation of medical, social, and functional deficits. Building on this model, Minitski et al. describe the development of a biological index that proves to be a reasonable method to predict mortality when compared to other frailty measurements. Strengths include its ability to import clinical measures, interchangeable components, and its potential ability to identify latent risk factors. Obstacles include the lack of a unifying biological theory related to aging, inclusion of costly research measures, and its inability to provide specific clues to the etiology of frailty according to the frailty index definition. Refinement in measures focused on aging-related biological changes rather than using measures that result from chronic disease states could help provide important biological insights and aid in the development of future treatment and preventive modalities.Please see related article: http://www.biomedcentral.com/1741-7015/13/161 . PMID- 26265078 TI - Medical schools should prohibit financial ties between individual academics and industry. PMID- 26265079 TI - The effect of solids residence time on phosphorus adsorption to hydrous ferric oxide floc. AB - The impact of solids residence time (SRT) on phosphate adsorption to hydrous ferric oxide (HFO) floc when striving for ultra-low P concentrations was characterized and an equilibrium model that describes the adsorption of P onto HFO floc of different ages was developed. The results showed that fresh HFO had a higher adsorption capacity in comparison to aged (2.8, 7.4, 10.8 and 22.8 days) HFO and contributed substantially to P removal at steady state. P adsorption onto HFO solids was determined to be best described by the Freundlich isotherm. P desorption from HFO solids was negligible supporting the hypothesis that chemisorption is the mechanism of P adsorption on HFO solids. A model that included the contribution of different classes of HFO solids (i.e. High, Low or Old, containing high concentration, low concentration or no active surface sites, respectively) to adsorption onto HFO from a sequencing batch reactor (SBR) system was found to adequately describe P adsorption onto HFO solids of different ages. From the model it was determined that the fractions of High and Low HFO decreased with SRT while the fraction of Old HFO increased with SRT. The transformation of High HFO to Low HFO did not limit the overall production of Old HFO and the fresh HFO solids contributed more to P removal at steady state than the aged solids. PMID- 26265080 TI - Support for gay men: an Australian study. AB - Recently, research in the U.S.A. has shown that women, and young people in particular, have become increasingly supportive of gay men. The current study used a cross-sectional, correlational design to investigate these same issues in Australia. The sample included 575 heterosexual participants, 184 men and 390 women. Because a literature search failed to identify an Australian measure of support for gay men, a Support for Gay Men Scale was developed by the researchers. Multiple regression analyses were used to investigate whether scores on the Brief Multidimensional Measure of Religiousness/Spirituality and the respondents' sex predicted scores on the Support for Gay Men subscales, and the strength of these relationships. Findings reveal that this relatively young university undergraduate Australian sample indicated they strongly supported gay men. PMID- 26265081 TI - Characterization of a heterobimetallic nonheme Fe(III)-O-Cr(III) species formed by O2 activation. AB - We report the generation and spectroscopic characterization of a heterobimetallic [(TMC)Fe(III)-O-Cr(III)(OTf)4] species (1) by bubbling O2 into a mixture of Fe(TMC)(OTf)2 and Cr(OTf)2 in NCCH3. Complex 1 also formed quantitatively by adding Cr(OTf)2 to [Fe(IV)(O)(TMC)(NCCH3)](2+). The proposed O2 activation mechanism involves the trapping of a Cr-O2 adduct by Fe(TMC)(OTf)2. PMID- 26265082 TI - Phase separation and crystallization in sodium lanthanum phosphate glasses induced by electrochemical substitution of sodium ions with protons. AB - Electrochemical substitution of sodium ions with protons (alkali-proton substitution; APS), and the injection of proton carriers was applied to sodium lanthanum phosphate glasses. A clear and homogeneous material was obtained for a glass of composition 25NaO1/2-8LaO3/2-66PO5/2-1GeO2 following APS, with a resulting proton conductivity of 4 * 10(-6) S cm(-1) at 250 degrees C. The glass underwent phase separation and crystallization at temperatures >255 degrees C, forming a highly hygroscopic and proton conducting H3PO4 phase in addition to LaP5O14 and other unidentified phases. A glass of composition 25NaO1/2-8LaO3/2 67PO5/2 underwent phase separation and crystallization during APS, forming both H3PO4 and LaP5O14 phases. Sodium lanthanum phosphate glasses are prone to phase separation and crystallization during APS unlike the previously reported NaO1/2 WO3-NbO5/2-LaO3/2-PO5/2 glasses. The phase separation was explained by a reduction in viscosity following APS and the introduction of protons, which exhibit high field strength. Thus, phase separation and crystallization of glasses during APS was difficult to avoid. An approach to suppress phase separation is discussed. PMID- 26265083 TI - Corrigendum: Salicylic acid biosynthesis is enhanced and contributes to increased biotrophic pathogen resistance in Arabidopsis hybrids. PMID- 26265084 TI - Differing roles for TGF-beta/Smad signaling in osteitis in chronic rhinosinusitis with and without nasal polyps. AB - BACKGROUND: Chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) and with nasal polyps (CRSwNP) is reported to involve different inflammatory processes in sinonasal mucosa and bone tissue, and these processes remain uncharacterized. OBJECTIVE: We aimed to investigate the molecular mechanisms of osteitis in Chinese patients with CRS to better understand the pathogenesis of CRS. METHODS: The study included 10 controls, 16 patients with CRSsNP, and 23 patients with CRSwNP. Ethmoid bone tissue samples were evaluated by histologic examination. Quantitative real-time reverse transcription polymerase chain reaction was used to assess expression of transforming growth factor (TGF) beta1, TGF-beta receptor I and II, Smad2, and Smad3. Immunohistochemical examination of osteoblast expression of TGF-beta1, TGF-beta receptor I and II, phosphorylated (p) Smad2, and p-Smad3 in ethmoid bone tissue was also performed. RESULTS: The histopathologic evaluation of ethmoid sinus bone tissue showed that eosinophils had infiltrated the periosteum and induced TGF-beta1 expression, periosteal thickening, increased osteoblast activity, and neo-osteogenesis. Messenger RNA levels of TGF-beta1, TGF-beta receptor I, and Smad3 in CRSwNP ethmoid bone tissues were significantly higher than those in ethmoid bone tissues of patients with CRSsNP and the controls. Immunohistochemical staining showed that TGF-beta1, TGF-beta receptor I, p-Smad2, and p-Smad3 protein expression was upregulated in patients with CRSwNP, consistent with the corresponding messenger RNA levels. CONCLUSION: Different signaling pathways are involved in osteitis in CRS and are activated by the TGF-beta/Smad signaling pathway in CRSwNP versus the TGF beta/Smad-independent signaling pathway in CRSsNP. Eosinophil infiltration of the periosteum, along with TGF-beta1 expression, in CRSwNP indicates that eosinophils may play an important role in the bone remodeling process in CRSwNP. PMID- 26265085 TI - SDF-1/CXCR4/CXCR7 is pivotal for vascular smooth muscle cell proliferation and chronic allograft vasculopathy. AB - Chronic rejection remains a major obstacle in transplant medicine. Recent studies suggest a crucial role of the chemokine SDF-1 on neointima formation after injury. Here, we investigate the potential therapeutic effect of inhibiting the SDF-1/CXCR4/CXCR7 axis with an anti-SDF-1 Spiegelmer (NOX-A12) on the development of chronic allograft vasculopathy. Heterotopic heart transplants from H-2bm12 to B6 mice and aortic transplants from Balb/c to B6 were performed. Mice were treated with NOX-A12. Control animals received a nonfunctional Spiegelmer (revNOX A12). Samples were retrieved at different time points and analysed by histology, RT-PCR and proliferation assay. Blockade of SDF-1 caused a significant decrease in neointima formation as measured by intima/media ratio (1.0 +/- 0.1 vs. 1.8 +/- 0.1, P < 0.001 AoTx; 0.35 +/- 0.05 vs. 1.13 +/- 0.27, P < 0.05 HTx). In vitro treatment of primary vascular smooth muscle cells with NOX-A12 showed a significant reduction in proliferation (0.42 +/- 0.04 vs. 0.24 +/- 0.03, P < 0.05). TGF-beta, TNF-alpha and IL-6 levels were significantly reduced under SDF-1 inhibition (3.42 +/- 0.37 vs. 1.67 +/- 0.33, P < 0.05; 2.18 +/- 0.37 vs. 1.0 +/- 0.39, P < 0.05; 2.18 +/- 0.26 vs. 1.6 +/- 0.1, P < 0.05). SDF-1/CXCR4/CXCR7 plays a critical role in the development of chronic allograft vasculopathy (CAV). Therefore, pharmacological inhibition of SDF-1 with NOX-A12 may represent a therapeutic option to ameliorate chronic rejection changes. PMID- 26265086 TI - Pseudocheckerboard pattern: an interesting histopathological finding in mechanic's hands. AB - BACKGROUND: Mechanic's hands are a well-known symptom often associated with dermatomyositis and are similar to hand eczema clinically. Histopathology of them usually shows hyperkeratosis, focal parakeratosis, psoriasiform acanthosis, basal vacuolar changes and necrotic keratinocytes in the epidermis and upper dermal mucin deposition. However, there have been few comparative histopathologic evaluations of mechanic's hands and palmoplantar eczema. METHODS: We evaluated the histopathology of mechanic's hands in 6 patients with dermatomyositis who visited our hospital between 2006 and 2014 comparing with histopathology of 27 patients with palmoplantar eczema, retrospectively. RESULTS: As previously reported, hyperkeratosis, basal vacuolar change and necrotic keratinocytes were seen in all cases of mechanic's hands. Basal vacuolar change was not observed in any cases of palmoplantar eczema. Three cases of mechanic's hands demonstrated a characteristic finding, a pseudocheckerboard pattern, in the hyperkeratotic horny layer; there were areas of alternating parakeratosis and orthokeratosis in a vertical arrangement and these areas alternated with the completely orthokeratotic areas in a horizontal arrangement. This pattern has not been focused in mechanic's hands so far. Same pattern was also observed in four patients with palmoplantar eczema. CONCLUSION: 'Pseudocheckerboard pattern' was not specific but may be a possible diagnostic clue for mechanic's hands. PMID- 26265089 TI - Copper catalyzed oxygen assisted C(CNOH)-C(alkyl) bond cleavage: a facile conversion of aryl/aralkyl/vinyl ketones to aromatic acids. AB - A novel copper-catalyzed aerobic oxidative C(NOH)-C(alkyl) bond cleavage reaction of aryl/aralkyl/vinyl ketones for the synthesis of aromatic/acrylic acids is described. A series of ketones having aryl/aralkyl/vinyl at the one end and methyl to any higher alkyl at the other end can be selectively cleaved and converted into the corresponding acids via oxime intermediates. PMID- 26265087 TI - Birth location preferences of mothers and fathers in rural Ghana: Implications for pregnancy, labor and birth outcomes. AB - BACKGROUND: Maternal deaths in Sub-Saharan Africa are largely preventable with health facility delivery assisted by skilled birth attendants. Examining associations of birth location preferences on pregnant women's experiences is important to understanding delays in care seeking in the event of complications. We explored the influence of birth location preference on women's pregnancy, labor and birth outcomes. METHODS: A qualitative study conducted in rural Ghana consisted of birth narratives of mothers (n = 20) who experienced pregnancy/labor complications, and fathers (n = 18) whose partners experienced such complications in their last pregnancy. All but two women in our sample delivered in a health facility due to complications. We developed narrative summaries of each interview and iteratively coded the interviews. We then analyzed the data through coding summaries and developed analytic matrices from coded transcripts. RESULTS: Birth delivery location preferences were split for mothers (home delivery-9; facility delivery-11), and fathers (home delivery-7; facility delivery-11). We identified two patterns of preferences and birth outcomes: 1) preference for homebirth that resulted in delayed care seeking and was likely associated with several cases of stillbirths and postpartum morbidities; 2) Preference for health facility birth that resulted in early care seeking, and possibly enabled women to avoid adverse effects of birth complications. CONCLUSION: Safe pregnancy and childbirth interventions should be tailored to the birth location preferences of mothers and fathers, and should include education on the development of birth preparedness plans to access timely delivery related care. Improving access to and the quality of care at health facilities will also be crucial to facilitating use of facility based delivery care in rural Ghana. PMID- 26265090 TI - Extremely preterm infants small for gestational age are at risk for motor impairment at 3 years corrected age. AB - BACKGROUND: Few studies have targeted psychomotor development and associated perinatal risk factors in Japanese very low birth weight (VLBW) infants who are severely small for gestational age (SGA). DESIGN/SUBJECTS: A single-center study was conducted in 104 Japanese VLBW infants who were born preterm, due to maternal, umbilical cord, or placental abnormalities, between 2000 and 2007. Psychomotor development as a developmental quotient (DQ) was assessed using the Kyoto Scale of Psychological Development at 3 years corrected age. Severely SGA was defined as birth weight or length below -2 standard deviation values of the mean values at the same gestation. VLBW infants were divided into 2 subgroups based on gestational age at birth: ?28 weeks (n=64) and <28 weeks (n=40). DQs of infants with severe SGA were compared with those of infants who were appropriate for gestational age (AGA). Factors associated with developmental disabilities in VLBW infants with severe SGA (n=23) were determined. RESULTS: In the group born at ?28 weeks gestation, infants with severe SGA had normal DQ values and did not significantly differ from those with AGA. However, in the group born at <28 weeks gestation, severe SGA infants had significantly lower postural-motor DQ values than AGA infants. Gestational age <28 weeks was an independent factor for low postural-motor DQ, regardless of the cause of severe SGA or pregnancy termination. CONCLUSIONS: Extremely preterm newborns with severe SGA are at risk of motor developmental disability at age 3 years. PMID- 26265091 TI - Continuous versus step-by-step scanning mode of a novel 3D scanner for CyberKnife measurements. AB - The purpose of the study is to investigate the continuous versus step-by-step scanning mode of a commercial circular 3D scanner for commissioning measurements of a robotic stereotactic radiosurgery system. The 3D scanner was used for profile measurements in step-by-step and continuous modes with the intent of comparing the two scanning modes for consistency. The profile measurements of in plane, cross-plane, 15 degree, and 105 degree were performed for both fixed cones and Iris collimators at depth of maximum dose and at 10cm depth. For CyberKnife field size, penumbra, flatness and symmetry analysis, it was observed that the measurements with continuous mode, which can be up to 6 times faster than step-by step mode, are comparable and produce scans nearly identical to step-by-step mode. When compared with centered step-by-step mode data, a fully processed continuous mode data gives rise to maximum of 0.50% and 0.60% symmetry and flatness difference respectfully for all the fixed cones and Iris collimators studied. PMID- 26265092 TI - Multi-objective experimental design for (13)C-based metabolic flux analysis. AB - (13)C-based metabolic flux analysis is an excellent technique to resolve fluxes in the central carbon metabolism but costs can be significant when using specialized tracers. This work presents a framework for cost-effective design of (13)C-tracer experiments, illustrated on two different networks. Linear and non linear optimal input mixtures are computed for networks for Streptomyces lividans and a carcinoma cell line. If only glucose tracers are considered as labeled substrate for a carcinoma cell line or S. lividans, the best parameter estimation accuracy is obtained by mixtures containing high amounts of 1,2-(13)C2 glucose combined with uniformly labeled glucose. Experimental designs are evaluated based on a linear (D-criterion) and non-linear approach (S-criterion). Both approaches generate almost the same input mixture, however, the linear approach is favored due to its low computational effort. The high amount of 1,2-(13)C2 glucose in the optimal designs coincides with a high experimental cost, which is further enhanced when labeling is introduced in glutamine and aspartate tracers. Multi objective optimization gives the possibility to assess experimental quality and cost at the same time and can reveal excellent compromise experiments. For example, the combination of 100% 1,2-(13)C2 glucose with 100% position one labeled glutamine and the combination of 100% 1,2-(13)C2 glucose with 100% uniformly labeled glutamine perform equally well for the carcinoma cell line, but the first mixture offers a decrease in cost of $ 120 per ml-scale cell culture experiment. We demonstrated the validity of a multi-objective linear approach to perform optimal experimental designs for the non-linear problem of (13)C metabolic flux analysis. Tools and a workflow are provided to perform multi objective design. The effortless calculation of the D-criterion can be exploited to perform high-throughput screening of possible (13)C-tracers, while the illustrated benefit of multi-objective design should stimulate its application within the field of (13)C-based metabolic flux analysis. PMID- 26265093 TI - Measurement of Free Versus Total Therapeutic Monoclonal Antibody in Pharmacokinetic Assessment is Modulated by Affinity, Incubation Time, and Bioanalytical Platform. AB - Decisions about efficacy and safety of therapeutic proteins (TP) designed to target soluble ligands are made in part by their ex vivo quantification. Ligand binding assays (LBAs) are critical tools in measuring serum TP levels in pharmacokinetic, toxicokinetic, and pharmacodynamic studies. This study evaluated the impact of reagent antibody affinities, assay incubation times, and analytical platform on free or total TP quantitation. An ELISA-based LBA that measures monoclonal anti-sclerostin antibody (TPx) was used as the model system. To determine whether the method measures free or total TPx, the effects of K on, K off, and K D were determined. An 8:1 molar ratio of sclerostin (Scl) to TPx compared to a 1:1 molar ratio produced by rabbit polyclonal antibodies to TPx was required to achieve IC50, a measure of TPx interference effectiveness, making it unclear whether the ELISA truly measured free TPx. Kinetic analysis revealed that Scl had a rapid dissociation rate (K off) from TPx and that capture and detection antibodies had significantly higher binding affinities (K D) to TPx. These kinetic limitations along with long ELISA incubation times lead to the higher molar ratios (8:1) required for achieving 50% inhibition of TPx. However, a microfluidic platform with the same reagent pairs required shorter incubations to achieve a lower Scl IC50 molar ratio (1:1). The findings from this study provide the bioanalytical community with a deeper understanding of how reagent and platform selection for LBAs can affect what a particular method measures, either free or total TP concentrations. PMID- 26265094 TI - Visual Predictive Check in Models with Time-Varying Input Function. AB - The nonlinear mixed effects models are commonly used modeling techniques in the pharmaceutical research as they enable the characterization of the individual profiles together with the population to which the individuals belong. To ensure a correct use of them is fundamental to provide powerful diagnostic tools that are able to evaluate the predictive performance of the models. The visual predictive check (VPC) is a commonly used tool that helps the user to check by visual inspection if the model is able to reproduce the variability and the main trend of the observed data. However, the simulation from the model is not always trivial, for example, when using models with time-varying input function (IF). In this class of models, there is a potential mismatch between each set of simulated parameters and the associated individual IF which can cause an incorrect profile simulation. We introduce a refinement of the VPC by taking in consideration a correlation term (the Mahalanobis or normalized Euclidean distance) that helps the association of the correct IF with the individual set of simulated parameters. We investigate and compare its performance with the standard VPC in models of the glucose and insulin system applied on real and simulated data and in a simulated pharmacokinetic/pharmacodynamic (PK/PD) example. The newly proposed VPC performance appears to be better with respect to the standard VPC especially for the models with big variability in the IF where the probability of simulating incorrect profiles is higher. PMID- 26265095 TI - Erratum to: Is Extrapolation of the Safety and Efficacy Data in One Indication to Another Appropriate for Biosimilars? PMID- 26265096 TI - A Structural Ensemble for the Enzyme Cyclophilin Reveals an Orchestrated Mode of Action at Atomic Resolution. AB - For enzyme activity, an exact structural and motional orchestration of the active site and its surroundings is believed to be key. In order to reveal such possible phenomena at atomic resolution on the basis of experimental evidence, an experimental restraint driven two-state ensemble of the prototypical enzyme cyclophilin was determined by using a recently introduced exact NOE approach. The ensemble description reveals the presence of an open and a closed state of cyclophilin, which is indicative of large-scale correlated motion. In the open state, the catalytic site is preorganized for catalysis, thus suggesting the mechanism of action to be conformational sampling, while the ligand-binding loop appears to act through an induced fit mechanism. This finding is supported by affinity measurements of a cyclophilin designed to be more open. Overall, more than 60-70 % of the side-chain conformations of cyclophilin appear to be correlated. PMID- 26265097 TI - Specificity for each of the 46 criteria of the Selvester QRS score for electrocardiographic myocardial scar sizing in left bundle branch block. AB - BACKGROUND: The Selvester QRS score consists of a set of electrocardiographic criteria designed to identify, quantify and localize scar in the left ventricle using the morphology of the QRS complex. These criteria were updated in 2009 to expand their use to patients with underlying conduction abnormalities, but these versions have thus far only been validated in small and carefully selected populations. AIM: To determine the specificity for each of the criteria of the left bundle branch block (LBBB) modified Selvester QRS Score (LB-SS) in a population with strict LBBB and no myocardial scar as verified by cardiovascular magnetic resonance imaging with late gadolinium enhancement (CMR-LGE). METHODS: We identified ninety-nine patients with LBBB without scar on CMR-LGE, who underwent a clinically indicated CMR scan at three different centers. The ECG recording date was any time prior to or <30days after the CMR scan. The LB-SS was applied and specificity for detection of scar in each of the 46 separate criteria was determined. RESULTS: The specificity ranged between 41% and 100% for the 46 criteria of LB-SS and 27/46 (59%) met >=95% specificity. The mean+/-SD specificity was 90%+/-14%. CONCLUSION: Several of the criteria in the LB-SS lack adequate specificity. Elimination or modification of these nonspecific QRS morphology criteria may improve the specificity of the overall LB-SS. PMID- 26265098 TI - Population plasma and urine pharmacokinetics of ivabradine and its active metabolite S18982 in healthy Korean volunteers. AB - Ivabradine, a selective inhibitor of the pacemaker current (If ), is used for heart failure and coronary heart disease and is mainly metabolized to S18982. The purpose of this study was to explore the pharmacokinetics (PK) of ivabradine and S18982 in healthy Korean volunteers. Subjects in a phase I study were randomized to receive 2.5, 5, or 10 mg of ivabradine administered every 12 hours for 4.5 days, and serial plasma and urine concentrations of ivabradine and S18982 were measured. The plasma PK of ivabradine was best described by a 2-compartment model with mixed 0- and first-order absorption, linked to a 2-compartment model for S18982. The introduction of interoccasional variabilities and period as covariate into absorption-related parameters improved the model fit. Urine data have been applied to estimate renal and nonrenal clearance, enabling a more detailed description of the elimination process. We developed a population PK model describing the plasma and urine PK of ivabradine and S18982 in healthy Korean adult males. This model might be useful for predicting the plasma and urine PK of ivabradine, potentially helping to identify the optimal dosing regimens in various clinical situations. PMID- 26265099 TI - Evaluating Intestinal Permeability by Measuring Plasma Endotoxin and Diamine Oxidase in Children with Acute Lymphoblastic Leukemia Treated with High-dose Methotrexate. AB - BACKGROUND AND AIM: The incidence of acute lymphoblastic leukemia (ALL) is highest in childhood malignant tumor in China. The high-dose methotrexate (HDMTX) treatment is very effective in ALL, and it can improve event-free survival rate. However, while executing the anti-tumor effect, it produces highly toxic effects on rapidly dividing cells which are normal. It seems probable that the HDMTX treatment injures intestinal mucosal barrier. The changes of intestinal mucosal barrier can be evaluated through measuring the level of plasma endotoxin and diamine oxidase (DAO). METHOD: Blood samples were collected from 30 normal children and 30 children with ALL at 1h, 24h, 44h and 68h after HDMTX. The levels of plasma endotoxin and DAO were measured at 1h, 24h, 44h and 68h after HDMTX with spectrophotometry. The levels of endotoxin and DAO were also measured in 4 different courses in 7 children with ALL. RESULTS: The levels of plasma endotoxin and DAO at 1h, 24h, 44h and 68h after HDMTX were higher than in normal children (P<0.01). The levels of plasma endotoxin and DAO at 24h and 44h after HDMTX were both higher than at 1h and 68h (P<0.01). There was no significant difference found in the measured results of plasma endotoxin and DAO at 1h and 68h after HDMTX (P>0.05). There was no significant difference found in the increased levels of endotoxin and DAO at 1h, 24h, 44h and 68h after HDMTX in 4 different courses of 7 children with ALL(P>0.05). CONCLUSION: By measuring the level of plasma endotoxin and DAO in children with ALL and during HDMTX chemotherapy, the results suggest that there is increased intestinal permeability. PMID- 26265101 TI - Quality Matters, Doesn't It? PMID- 26265100 TI - Evolutionarily advanced ant farmers rear polyploid fungal crops. AB - Innovative evolutionary developments are often related to gene or genome duplications. The crop fungi of attine fungus-growing ants are suspected to have enhanced genetic variation reminiscent of polyploidy, but this has never been quantified with cytological data and genetic markers. We estimated the number of nuclei per fungal cell for 42 symbionts reared by 14 species of Panamanian fungus growing ants. This showed that domesticated symbionts of higher attine ants are polykaryotic with 7-17 nuclei per cell, whereas nonspecialized crops of lower attines are dikaryotic similar to most free-living basidiomycete fungi. We then investigated how putative higher genetic diversity is distributed across polykaryotic mycelia, using microsatellite loci and evaluating models assuming that all nuclei are either heterogeneously haploid or homogeneously polyploid. Genetic variation in the polykaryotic symbionts of the basal higher attine genera Trachymyrmex and Sericomyrmex was only slightly enhanced, but the evolutionarily derived crop fungi of Atta and Acromyrmex leaf-cutting ants had much higher genetic variation. Our opposite ploidy models indicated that the symbionts of Trachymyrmex and Sericomyrmex are likely to be lowly and facultatively polyploid (just over two haplotypes on average), whereas Atta and Acromyrmex symbionts are highly and obligatorily polyploid (ca. 5-7 haplotypes on average). This stepwise transition appears analogous to ploidy variation in plants and fungi domesticated by humans and in fungi domesticated by termites and plants, where gene or genome duplications were typically associated with selection for higher productivity, but allopolyploid chimerism was incompatible with sexual reproduction. PMID- 26265102 TI - Meta-analytic research on the relationship between cumulative risk alleles and risk of type 2 diabetes mellitus. AB - BACKGROUND: Our aim is to examine the dose-response association between cumulative genetic risk and actual risk of type 2 diabetes mellitus (T2DM) and the influence of adjustment for covariates on T2DM risk through a comprehensive meta-analysis of observational studies. METHODS: Electronic literature search using EMBASE and MEDLINE (from 2003 to 2014) was conducted for cross-sectional or longitudinal studies that presented the odds ratio (OR) for T2DM in each group with categories based on the total number of risk alleles (RAs) carried (RAtotal ) using at least two single-nucleotide polymorphisms. Spline regression model was used to determine the shape of the relationship between the difference from the referent group of each study in RAtotal (DeltaRAtotal ) and the natural logarithms of ORs (log OR) for T2DM. RESULTS: Sixty-five eligible studies that included 68 267 cases among 182 603 participants were analysed. In both crude and adjusted ORs, defined by adjusting the risk for at least two confounders among age, gender and body mass index, the slope of the log OR for T2DM became less steep as the DeltaRAtotal increased. In the analysis limited to 14 cross sectional and four longitudinal studies presenting both crude and adjusted ORs, regression curves of both ORs in relation to DeltaRAtotal were almost identical. CONCLUSION: Using only single-nucleotide polymorphisms for T2DM screening was of limited value. However, when genotypic T2DM risk was considered independently from risk in relation to covariates, it was suggested that genetic profiles might have a supplementary role related to conventional T2DM risk factors in identifying individuals at high risk of T2DM. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26265103 TI - A Robust and Cost-Effective Superhydrophobic Graphene Foam for Efficient Oil and Organic Solvent Recovery. AB - Water pollution caused by chemical reagent leaking, industrial wastewater discharging, and crude oil spills has raised global concerns on environmental sustainability, calling for high-performance absorbent materials for effective treatments. However, low-cost materials capable of effectively separating oils and organic solvents from water with a high adsorption capacity and good recyclability are rare on the market. Here, a cost-effective method is reported to fabricate high-performance graphene modified absorbents through the facile thermal reduction of graphene oxide on the skeletons of melamine foam. By integrating the high porosity, superior elasticity, and mechanical stability of raw sponge with the chemical stability and hydrophobicity of graphene sheets, the as-fabricated graphene foam not only possesses a rough and superhydrophobic surface, but also exhibits an excellent adsorption performance and extraordinary recyclability for various oils and organic solvents. It is worth mentioning that the superhydrophobic surface also endows the graphene foam with an excellent efficiency for oil/water separation. More importantly, the cost-effective fabrication method without involving expensive raw materials and sophisticated equipment permits a scale-up of the graphene foam for pollution disposal. All these features make the graphene foam an ideal candidate for removal and collection of oils and organic solvents from water. PMID- 26265104 TI - Causative drug detection by drug-induced lymphocyte stimulation test in drug induced linear IgA bullous dermatosis. PMID- 26265105 TI - REM sleep behavior disorder and neuropathology in Parkinson's disease. AB - INTRODUCTION: Rapid eye movement (REM) sleep behavior disorder (RBD) in Parkinson's disease (PD) is associated with differences in clinical phenotype, including dementia, autonomic loss, and gait dysfunction. The pathological basis for this remains unclear. METHODS: Parkinson's disease subjects in a longitudinal clinicopathologic study were screened for probable RBD with the Mayo Sleep Questionnaire. After death, semiquantitative analyses were conducted for synuclein, amyloid, neurofibrillary tangles, and cerebrovascular lesions. RESULTS: Forty cases had probable RBD (PD+RBD), and 41 did not (PD-RBD). Despite similar age at death (~80 y) and disease duration (~14.5 y), PD+RBD had increased synuclein deposition in all regions examined, with nine of 10 regions significantly different. The Lewy body 10-region total score (scale = 0-40) was 29.5 in PD+RBD versus 24.5 in PD-RBD (Cohen-d effect size = 0.79, P = 0.002). Cerebrovascular lesion burden was slightly higher in PD-RBD. CONCLUSIONS: Although overlap occurs between groups, PD patients with probable RBD may have greater density and range of synuclein pathology on autopsy. PMID- 26265106 TI - Biphasic Effect of Basic Fibroblast Growth Factor on Anterior Pituitary Folliculostellate TtT/GF Cell Coupling, and Connexin 43 Expression and Phosphorylation. AB - Basic fibroblast growth factor (bFGF) is a mitogenic and differentiating cytokine. In the anterior pituitary, folliculostellate (FS) cells constitute the major source of bFGF. bFGF affects endocrine cell proliferation and secretion in the anterior pituitary. In addition, bFGF increases its own expression by acting directly on FS cells. FS cell Cx43-mediated gap junction intercellular communication allows the establishment of an intrapituitary network for the transmission of information. In the present study, we assessed how bFGF regulates FS cell coupling. Time course studies were carried out on the FS cell line TtT/GF. Short-term bFGF treatment induced a transient cell uncoupling and the phosphorylation in Ser368 of membrane-bound Cx43 without modifying Cx43 levels. We demonstrated the involvement of the protein kinase C (PKC) isoform alpha in the phosphorylation of Cx43 in S368. Moreover, we showed that bFGF induced PKCalpha activation by stimulating its expression, phosphorylation and association with the plasma membrane. The long-term incubation with bFGF increased TtT/GF cell coupling, total Cx43 levels and Cx43 accumulation at the cell membrane of cytoplasmic projections. The Cx43 level increase was a result of the stimulation of Cx43 gene transcription as mediated by the extracellular regulated kinase 1/2 signalling pathway. Taken together, the data show that bFGF modulates TtT/GF cell coupling by activating different pathways that lead to opposite effects on Cx43 phosphorylation and expression depending on the duration of the exposure of the cells to bFGF. A short-term bFGF exposure reduces cell-to cell communication as a mean of desynchronising FS cells. By contrast, long-term exposure to bFGF enhances cell-to-cell communication and facilitates coordination among FS cells. PMID- 26265107 TI - Non-neoplastic parenchymal changes in kidney cancer and post-partial nephrectomy recovery of renal function. AB - OBJECTIVE: To explore the association of non-neoplastic parenchymal changes (nNPC) with patients' health and renal function recovery after partial nephrectomy (PN). MATERIALS AND METHODS: This retrospective review identified 800 pT1a patients who underwent PN at Memorial Sloan Kettering Cancer Center from 2007 to 2012. Pathology reports were reviewed for nNPC graded as mild or severe: vascular sclerosis (VS), glomerulosclerosis (GS), and fibrosis/scarring. Correlations between nNPC and known preoperative predictors of renal function [age, sex, African-American race, estimated glomerular filtration rate (eGFR), American Society of Anesthesiologists (ASA) score, body mass index, coronary artery disease, and hypertension (HTN)] were assessed using Spearman's rank correlation (rho). Multivariable linear regression, adjusted for the described known preoperative risk predictors, was performed to evaluate whether the parenchymal features were able to predict 6-month postoperative eGFR. RESULTS: In this study, 46 % of tumors had benign surrounding parenchyma. We noted statistically significant yet weak associations of VS with age (rho = 0.19; p < 0.001), ASA (rho = 0.09; p < 0.001), preoperative eGFR (rho = -0.14; p < 0.001), and HTN (rho = 0.14; p < 0.001). GS also significantly correlated with HTN, but the correlation was again small (rho = 0.12; p < 0.001). After adjusting for known risk predictors, only GS was a significant predictor of 6-month postoperative eGFR. When compared with no GS, mild and severe GS were negatively associated with a decrease of 4.9 and 10.8 mL/min/1.73 m(2) in 6-month postoperative eGFR, respectively. CONCLUSIONS: Presence of VS and GS correlated with patients' baseline health, and presence of GS predicted postoperative renal function recovery. PMID- 26265108 TI - Relationship between mild-to-moderate chronic kidney disease and decreased bone mineral density in Chinese adult population. AB - BACKGROUND: Several studies have shown ethnic differences in bone and mineral metabolism in healthy people and patients with chronic kidney disease (CKD). However, there have been few studies regarding CKD and bone mineral density (BMD) in Chinese population. We aimed to explore the relationship between mild-to moderate CKD and decreased BMD in Chinese adult population. METHODS: A total of 24,002 adults were enrolled in this cross-sectional study. Mild-to-moderate CKD was defined as 30 < estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) or eGFR >= 60 mL/min/1.73 m(2) with proteinuria greater than 1+. BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine. Either osteopenia or osteoporosis was defined as decreased BMD. Multivariate logistic regression analysis was used to estimate the associations with decreased BMD. RESULTS: The subjects comprised 71.5 % men and 28.5 % women, the age was 49.9 +/- 13.9 years. The overall prevalence of CKD was 2.9 %. Decreased BMD was 22.1, 19.9 % had osteopenia, and 2.2 % had osteoporosis. The percentage of patients with decreased BMD, osteopenia and osteoporosis were statistically higher (P < 0.05) in CKD patients compared with those of non-CKD participants, which was 29.5 versus 21.9 %, 25.9 versus 19.8 % and 3.6 versus 2.1 %, respectively. The risk for decreased BMD increased with CKD in a simple logistic analysis. However, the correlation disappeared after adjusted for age, sex, smoking, drinking, hypertension, diabetes and obesity. CONCLUSIONS: Subjects with worse renal function have significantly lower BMD, but after adjusted for confounders, mild to-moderate CKD is not independently associated with decreased BMD. PMID- 26265109 TI - Combination of warming blanket and prewarmed intravenous infusion is effective for rewarming in infants with postoperative hypothermia in China. AB - BACKGROUND: Postoperative hypothermia in the postanesthesia care unit (PACU) in neonates and infants is a well-known serious complication as it can increase the risk of blood loss, wound infections, and cardiac arrhythmias. AIM: To identify an effective rewarming method for neonates and infants in China with postoperative hypothermia, an open-label, randomized, and controlled study was performed to compare the effects of three different rewarming methods. METHODS: Neonates and infants (<1 year) admitted to the PACU after surgery between June 2011 and November 2012 in a local hospital were investigated. Patients diagnosed with hypothermia were randomly divided into three groups and rewarmed with only blanket (blanket group), blanket plus electric blanket (heating blanket group), and blanket plus prewarmed intravenous (i.v.) infusion (warmed infusion group). From the beginning of rewarming, the rectal temperature was recorded every 10 min up to 180 min. RESULTS: The incidence of postoperative hypothermia in neonates and infants was 5.9%. Patients rewarmed with warming blanket plus prewarmed i.v. infusions showed the shortest rewarming time (67.0 +/- 2.6 min, P = 0.02) and highest rewarming efficiency (0.027 +/- 0.0008 degrees C.min(-1) , P = 0.039). CONCLUSIONS: The combination of conventional blanket rewarming and prewarmed i.v. infusion was shown to be an effective rewarming method for hypothermic infants in China. PMID- 26265110 TI - The use of FNA samples for whole-exome sequencing and detection of somatic mutations in breast cancer surgical specimens. AB - BACKGROUND: The availability of suitable biospecimens is critical to the success of advanced genomic analyses. The objective of this study was to assess the sensitivity of fine-needle aspiration (FNA) compared with gross surgical sampling (GSS) from surgical specimens for the detection of somatic mutations in breast cancer using whole-exome sequencing (WES). METHODS: DNA was extracted from paired GSS tissues and FNA samples of surgically resected breast cancer from 12 patients and was used for WES. Sanger sequencing was performed to validate selected somatic mutations. Tumor purity was calculated for each sample using sequencing data. RESULTS: There was no difference in the total amount of DNA extracted from GSS tissues and FNA samples. WES was successfully performed for all 12 pairs of samples. The median number of somatic mutations identified in individual samples was higher in FNA samples than in GSS tissues (39.5 vs 18.5; P = .036). The somatic mutation profiles from both sampling methods were well correlated for samples that had GSS tissues with high tumor content, as indicated by hematoxylin and eosin staining. Nineteen mutations that were identified exclusively in FNA samples were subjected to Sanger sequencing, and 13 of those mutations (68.4%) were validated. The mean estimated tumor purity was higher in FNA samples than in GSS tissues (55.87% vs 25.76%), and FNA samples were estimated to have a consistently higher proportion of malignant cells. CONCLUSIONS: The current results suggest that FNA is feasible for the collection of tumor samples sufficient for WES analysis and that the higher purity obtained using this method may make it more reliable for genomic studies. PMID- 26265113 TI - T cell metabolism and susceptibility to autoimmune diseases. AB - During an immune response, T cell differentiation and function are tightly regulated to ensure protection against pathogens and prevent the autoimmune attack versus self-antigens. It is now established that cellular activation is coupled to profound changes in cellular metabolism. Indeed, pathways that control immune cell function and metabolism are intimately related, and different metabolic programs have been shown to control specific T cell fate. This review aims to provide an integrated view of T cell metabolism and of the molecular pathways controlling an appropriate T cell receptor (TCR) engagement. We describe here how different aspects of metabolism can influence T cell functions, focusing on the emerging role of the key metabolic pathways regulating T cell activation and their alterations in different autoimmune conditions. Manipulating these programs or their substrates could provide insights into mechanisms involved in inflammatory/autoimmune conditions, unveiling the potential for developing novel therapeutic approaches to treat these diseases. PMID- 26265112 TI - A mutant Synechococcus gene encoding glutamate 1-semialdehyde aminotransferase confers gabaculine resistance when expressed in tobacco plastids. AB - KEY MESSAGE: A mutant glutamate 1-semialdehyde aminotransferase gene from the Synechococcus , inserted into tobacco plastid DNA by means of particle bombardment and antibiotic selection, conferred gabaculine resistance allowing to attain homoplasmy. Many plant species are recalcitrant to plastid genome transformation. New selections systems may help to overcome this limitation and to extend the application of this technology. A mutant hemL gene from the photosynthetic cyanobacterium Synechococcus, encoding a gabaculine-insensitive glutamate 1-semialdehyde aminotransferase (GSA), is an efficient selectable marker gene for nuclear transformation of tobacco, alfalfa and durum wheat. Since GSA functions in the plastid, we introduced the mutant hemL gene into the tobacco plastid genome along with the conventional antibiotic resistance aadA gene, in the attempt to develop a new selection system for plastome transformation. Although we were unable to directly regenerate gabaculine resistant transplastomic plants, we demonstrated the functionality of hemL in tobacco plastids by using gabaculine selection in the second and third rounds of in vitro selection that permitted to obtain the homoplasmic state in transgenic plants. Thus, the mutant hemL gene functions as a secondary selection marker in tobacco plastids. Our results encourage further attempts to test gabaculine resistant GSA for plastome transformation of crop plants in which gabaculine has stronger regeneration-inhibiting effects with respect to tobacco. PMID- 26265114 TI - Sprouty2 suppresses the inflammatory responses in rheumatoid arthritis fibroblast like synoviocytes through regulating the Raf/ERK and PTEN/AKT signals. AB - AKT and ERK pathways are known to be activated in human rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS), which play crucial roles in the pathogenesis and joint destruction of RA. Sprouty2 (SPRY2) has been known as a tumor suppressor by preventing both ERK and AKT signaling activations. Whether SPRY2 can function as a suppressor in tumor-like inflammatory FLS through negatively regulating AKT and ERK pathways, has not been reported. The purpose of this study was to determine whether SPRY2 might have antiinflammatory effects on RA FLS. The recombinant adenovirus containing SPRY2 complementary DNA (AdSPRY2) was used to deliver SPRY2 and express the protein in RA FLS. Adenoviral vector encoding green fluorescent protein (AdGFP) was used as the control. AdSPRY2 treatment suppressed the production of proinflammatory cytokines and matrix metalloproteinases (MMPs), and the cell proliferation, induced by TNFalpha in RA FLS. SPRY2 overexpression reduced AKT and ERK phosphorylation in TNFalpha-stimulated FLS, through mediating or interfering with the activity of PTEN or Raf respectively. These results suggest that using SPRY2 to block the AKT and ERK pathways suppresses the inflammatory responses of RA FLS, and the development of an immunoregulatory strategy based on SPRY2 may therefore have therapeutic potential in the treatment of RA. PMID- 26265115 TI - Reasons for measles cases not being vaccinated with MMR: investigation into parents' and carers' views following a large measles outbreak. AB - Uptake rates for the combined measles, mumps and rubella (MMR) vaccine have been below the required 95% in the UK since a retracted and discredited article linking the MMR vaccine with autism and inflammatory bowel disease was released in 1998. This study undertook semi-structured telephone interviews among parents or carers of 47 unvaccinated measles cases who were aged between 13 months and 9 years, during a large measles outbreak in Merseyside. Results showed that concerns over the specific links with autism remain an important cause of refusal to vaccinate, with over half of respondents stating this as a reason. A quarter stated child illness during scheduled vaccination time, while other reasons included general safety concerns and access issues. Over half of respondents felt that more information or a discussion with a health professional would help the decision-making process, while a third stated improved access. There was clear support for vaccination among respondents when asked about current opinions regarding MMR vaccine. The findings support the hypothesis that safety concerns remain a major barrier to MMR vaccination, and also support previous evidence that experience of measles is an important determinant in the decision to vaccinate. PMID- 26265116 TI - Semi-parametric estimation of random effects in a logistic regression model using conditional inference. AB - This paper describes a new approach to the estimation in a logistic regression model with two crossed random effects where special interest is in estimating the variance of one of the effects while not making distributional assumptions about the other effect. A composite likelihood is studied. For each term in the composite likelihood, a conditional likelihood is used that eliminates the influence of the random effects, which results in a composite conditional likelihood consisting of only one-dimensional integrals that may be solved numerically. Good properties of the resulting estimator are described in a small simulation study. PMID- 26265117 TI - Superficial Femoral Artery Intervention: Creating an Algorithmic Approach for the Use of Old and Novel (Endovascular) Technologies. AB - OPINION STATEMENT: Femoropopliteal (FP) disease is a common presentation of peripheral arterial disease (PAD), and a challenging anatomic region for durable treatment. Surgical bypass has historically been the primary therapeutic modality, but has been supplanted in the last decade by endovascular therapy, even with the most complex presentation of disease. Endovascular therapy has the advantage of a more favorable and rapid recovery, while preserving future treatment options. Endovascular management of FP disease, initially with "Plain Old" balloon angioplasty (POBA) has yielded over the years to bare metal stents (BMS), and more recently, to technologies seeking to limit BMS use due to difficult-to-treat patterns of in-stent restenosis (ISR). Despite a myriad number of endovascular devices and strategies, the approach to FP intervention lends itself to an algorithmic schema largely predicated on lesion length, severity of calcification, recanalization method, and clinical goals based upon individual patient status. In addition, treatment costs are a growing consideration in device selection. These criteria can be summarized into what we have termed as a "CADENCE" approach to treatment, an acronym representing the following factors: Clinical scenario, Anatomy, Device performance specifications, Experience/Ease, Novelty, Cost, and Evidence-base (Fig. 1). While the individual components of the CADENCE strategy are not always hierarchical, they combine to give a framework for reasonable interventional strategies for a given patient presentation and lesion appearance. Since there is a notable lack of prospective data for FP interventions, most notably with regard to direct device comparisons, actual practice is often experiential, and further data to guide optimal patient care are needed. PMID- 26265118 TI - Barriers and Facilitators to Cervical Cancer Screening Among Women in Rural Ontario, Canada: The Role of Self-Collected HPV Testing. AB - PURPOSE: The addition of human papillomavirus (HPV) testing to primary cervical cancer screening provides an opportunity to employ less invasive cervical cancer screening modalities. The objective of this study was to explore the initial reaction and perception to HPV self-collected testing, in the context of current barriers and facilitators to cervical cancer screening, among women in an underscreened community in rural Ontario. METHODS: Age-stratified focus groups were conducted with women 18-70 years of age in rural Ontario to discuss cervical cancer screening. Women were recruited using purposive sampling of underscreened women and women in the general community. Qualitative thematic analysis of focus group transcripts identified the barriers, facilitators, and role of HPV self collected testing for cervical cancer screening. RESULTS: Four focus groups were conducted with a total of 25 women. Overall, women were very positive toward self collected HPV testing. HPV self-collected testing was felt to address many of the logistical (eg, inconvenient clinic hours, lack of time) and procedural barriers (embarrassment, lack of social distance in a small town) to current screening practices. However, self-collected HPV testing does not address barriers related to cervical cancer knowledge (eg, fear of cancer). Women identified issues related to test reliability, confidence in the ability to self-collect, and education around testing that would need to be addressed prior to implementation. Generational differences were noted in the acceptability of self-collected HPV testing between older and younger women. CONCLUSIONS: HPV self-collected testing was perceived as a facilitator for screening, and it was well accepted in this rural community. PMID- 26265119 TI - Transdermal granisetron versus palonosetron for prevention of chemotherapy induced nausea and vomiting following moderately emetogenic chemotherapy: a multicenter, randomized, open-label, cross-over, active-controlled, and phase IV study. AB - BACKGROUND: Palonosetron is the second-generation 5-hydroxytryptamine 3 receptor antagonist (5-HT3RA) that has shown better efficacy than the first-generation 5 HT3RA for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC). Granisetron transdermal delivery system (GTDS), a novel transdermal formulation, was developed to deliver granisetron continuously over 7 days. This study compared the efficacy and tolerability of the GTDS to palonosetron for the control of CINV following MEC. MATERIAL AND METHOD: A total of 196 patients were randomized to GP or PG group. In this multicenter, randomized, open-label, cross-over, active controlled, Phase IV study, GP group was assigned to receive transdermal granisetron (one GTDS patch, 7 days) in the first chemotherapy cycle, palonosetron (iv 0.25 mg/day, 1 days) in the second chemotherapy cycle before receiving MEC, and PG group was assigned to receive palonosetron in the first cycle and GTDS in the second cycle. Primary endpoint was the percentage of chemotherapy cycles achieving complete response (CR; defined as no emetic episodes and no rescue medication use) during the acute phase (0-24 h in post chemotherapy; non-inferiority comparison with palonosetron). RESULTS: Total 333 cycles (165 in GTDS and 168 in palonosetron) were included in the per protocol analysis. The GTDS cycles showed non-inferiority to palonosetron cycles during the acute phase: CR was achieved by 124 (75.2 %) patients in the GTDS cycles and 134 (79.8 %) patients in the palonosetron cycles (treatment difference, -4.6 %; 95 % confidence interval, -13.6-4.4). There was no significant difference in CR rate during acute phase after the end of the first and second chemotherapy cycle between GP and PG group (p = 0.405, p = 0.074). Patients' satisfaction, assessed using Functional Living Index-Emesis (FLI-E), GTDS cycle were higher than those of palonosetron cycle in GP group (FLI-E score; median 1549.5 in GTDS cycle, median 1670.0 in palonosetron cycle). Both treatments were well tolerated and safe. CONCLUSION: Transdermal granisetron is a good alternative therapeutic option to palonosetron for preventing CINV after MEC. PMID- 26265120 TI - Identification of Rab6a as a New Target of microRNA-155 Involved in Regulating Lipopolysaccharide-Induced TNF Secretion. AB - This study aims to provide experimental proof that Rab6a is an efficient target of microRNA-155 in regulating pro-inflammatory tumor necrosis factor (TNF) secretion stimulated by lipopolysaccharide (LPS) in macrophages. We identified Rab6a as a new target of microRNA-155 (miR-155) and found that overexpression of miR-155 decreased Rab6a expression at both protein and mRNA levels, which resulted in a significant reduction of TNF secretion induced by lipopolysaccharide stimulation. We have demonstrated that miR-155 can negatively regulate inflammatory TNF secretion in lipopolysaccharide stimulated macrophages, partly by targeting Rab6a, thereby providing new insights into the role of miR 155 in cytokine secretion in inflammatory macrophages. PMID- 26265121 TI - Conjugated oligoelectrolyte represses hydrogen oxidation by Geobacter sulfurreducens in microbial electrolysis cells. AB - A conjugated oligoelectrolyte (COE), which spontaneously aligns within cell membranes, was shown to completely inhibit H2 uptake by Geobacter sulfurreducens in microbial electrolysis cells. Coulombic efficiencies that were 490+/-95%, due to H2 recycling between the cathode and microorganisms on the anode, were reduced to 86+/-2% with COE addition. The use of the COE resulted in a 67-fold increase in H2 gas recovery, and a 4.4-fold increase in acetate removal. Current generation, H2 recovery and COD removals by Geobacter metallireducens, which cannot use H2, were unaffected by COE addition. These results show that this COE is an effective H2 uptake inhibitor, and that it can enable improved and sustained H2 gas recovery in this bioelectrochemical system. PMID- 26265123 TI - Influence of short incompatible practice on the Simon effect: transfer along the vertical dimension and across vertical and horizontal dimensions. AB - In spatial compatibility and Simon tasks, the response is faster when stimulus and response locations are on the same side than when they are on opposite sides. It has been shown that a spatial incompatible practice leads to a subsequent modulation of the Simon effect along the horizontal dimension. It has also been reported that this modulation occurs both along and across vertical and horizontal dimensions, but only after intensive incompatible training (600 trials). In this work, we show that this modulatory effect can be obtained with a smaller number of incompatible trials, changing the spatial arrangement of the vertical response keys to obtain a stronger dimensional overlap between the spatial codes of stimuli and response keys. The results of Experiment 1 showed that 80 incompatible vertical trials abolished the Simon effect in the same dimension. Experiment 2 showed that a modulation of the vertical Simon effect could be obtained after 80 horizontal incompatible trials. Experiment 3 explored whether the transfer effect can also occur in a horizontal Simon task after a brief vertical spatial incompatibility task, and results were similar to the previous experiments. In conclusion, we suggest that the spatial arrangement between response key and stimulus locations may be critical to establish the short-term memory links that enable the transfer of learning between brief incompatible practices and the Simon effects, both along the vertical dimension and across vertical and horizontal dimensions. PMID- 26265124 TI - Inertial torque during reaching directly impacts grip-force adaptation to weightless objects. AB - A hallmark of movement control expressed by healthy humans is the ability to gradually improve motor performance through learning. In the context of object manipulation, previous work has shown that the presence of a torque load has a direct impact on grip-force control, characterized by a significantly slower grip force adjustment across lifting movements. The origin of this slower adaptation rate remains unclear. On the one hand, information about tangential constraints during stationary holding may be difficult to extract in the presence of a torque. On the other hand, inertial torque experienced during movement may also potentially disrupt the grip-force adjustments, as the dynamical constraints clearly differ from the situation when no torque load is present. To address the influence of inertial torque loads, we instructed healthy adults to perform visually guided reaching movements in weightlessness while holding an unbalanced object relative to the grip axis. Weightlessness offered the possibility to remove gravitational constraints and isolate the effect of movement-related feedback on grip force adjustments. Grip-force adaptation rates were compared with a control group who manipulated a balanced object without any torque load and also in weightlessness. Our results clearly show that grip-force adaptation in the presence of a torque load is significantly slower, which suggests that the presence of torque loads experienced during movement may alter our internal estimates of how much force is required to hold an unbalanced object stable. This observation may explain why grasping objects around the expected location of the center of mass is such an important component of planning and control of manipulation tasks. PMID- 26265122 TI - Steroid hormones, steroid receptors, and breast cancer stem cells. AB - The ovarian hormones progesterone and estrogen play important roles in breast cancer etiology, proliferation, and treatment. Androgens may also contribute to breast cancer risk and progression. In recent years, significant advances have been made in defining the roles of these steroid hormones in stem cell homeostasis in the breast. Stem cells are potential origins of breast cancer and may dictate tumor phenotype. At least a portion of breast cancers are proposed to be driven by cancer stem cells (CSCs), cells that mimic the self-renewing and repopulating properties of normal stem cells, and can confer drug resistance. Progesterone has been identified as the critical hormone regulating normal murine mammary stem cell (MaSC) populations and normal human breast stem cells. Synthetic progestins increase human breast cancer risk; one theory speculates that this occurs through increased stem cells. Progesterone treatment also increases breast CSCs in established breast cancer cell lines. This is mediated in part through progesterone regulation of transcription factors, signal transduction pathways, and microRNAs. There is also emerging evidence that estrogens and androgens can regulate breast CSC numbers. The evolving concept that a breast CSC phenotype is dynamic and can be influenced by cell signaling and external cues emphasizes that steroid hormones could be crucial players in controlling CSC number and function. Here we review recent studies on steroid hormone regulation of breast CSCs, and discuss mechanisms by which this occurs. PMID- 26265125 TI - Mannitol and Outcome in Intracerebral Hemorrhage: Propensity Score and Multivariable Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 Results. AB - BACKGROUND AND PURPOSE: Mannitol is often used to reduce cerebral edema in acute intracerebral hemorrhage but without strong supporting evidence of benefit. We aimed to determine the impact of mannitol on outcome among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). METHODS: INTERACT2 was an international, open, blinded end point, randomized controlled trial of 2839 patients with spontaneous intracerebral hemorrhage (<6 hours) and elevated systolic blood pressure allocated to intensive (target systolic blood pressure, <140 mm Hg within 1 hour) or guideline recommended (target systolic blood pressure, <180 mm Hg) blood pressure-lowering treatment. Propensity score and multivariable analyses were performed to investigate the relationship between mannitol treatment (within 7 days) and poor outcome, defined by death or major disability on the modified Rankin Scale score (3-6) at 90 days. RESULTS: There was no significant difference in poor outcome between mannitol (n=1533) and nonmannitol (n=993) groups: propensity score matched odds ratio of 0.90 (95% confidence interval, 0.75-1.09; P=0.30) and multivariable odds ratio of 0.87 (95% confidence interval, 0.71-1.07; P=0.18). Although a better outcome was suggested in patients with larger (>=15 mL) than those with smaller (<15 mL) baseline hematomas who received mannitol (odds ratio, 0.52 [95% confidence interval, 0.35-0.78] versus odds ratio, 0.91 [95% confidence interval, 0.72-1.15]; P homogeneity<0.03 in propensity score analyses), the association was not consistent in analyses across other cutoff points (>=10 and >=20 mL) and for differing grades of neurological severity. Mannitol was not associated with excess serious adverse events. CONCLUSIONS: Mannitol seems safe but might not improve outcome in patients with acute intracerebral hemorrhage. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00716079. PMID- 26265127 TI - Nursing Interventions for Poststroke Fatigue. PMID- 26265126 TI - Drugs to Enhance Motor Recovery After Stroke. PMID- 26265128 TI - Cross-National Key Performance Measures of the Quality of Acute Stroke Care in Western Europe. AB - BACKGROUND AND PURPOSE: There are no agreed measures of stroke care quality that enable the standardized comparison of stroke care between countries. We aimed to develop a set of measures of quality of acute stroke care involving stroke quality registers in Western Europe. METHODS: A multinational working group identified 6 regional or national stroke quality registers in Europe and reviewed their data sets, performance measures, and the method by which these had been developed. Measures used in the registers were presented for discussion to a consensus group of representatives from the quality registers identified, as well as other stroke experts, and the final set of common performance measures was agreed through majority consensus. RESULTS: Thirty final performance measures were agreed by the European consensus group, encompassing the domains of coordination of care (stroke unit-based care), diagnosis (brain imaging, vascular imaging, cardiac arrhythmia detection, and therapy assessment), preservation of neural tissue (thrombolytic therapy and door-to-needle time), prevention of complications (dysphagia screening), initiation of secondary prevention (antiplatelet, anticoagulation, lipid lowering, blood pressure lowering, carotid surgery, time from vascular imaging to carotid surgery, and smoking cessation), survival (90-day poststroke mortality), and functional outcomes (90-day modified Rankin Scale). CONCLUSIONS: On the basis of experience of quality registers in Europe, we have proposed a common set of performance measures that will facilitate the international comparison of acute stroke care quality. PMID- 26265129 TI - Intracerebral Hematoma Contributes to Hydrocephalus After Intraventricular Hemorrhage via Aggravating Iron Accumulation. AB - BACKGROUND AND PURPOSE: The intraventricular hemorrhage (IVH) secondary to intracerebral hemorrhage (ICH) was reported to be relevant to a higher incidence of hydrocephalus, which would result in poorer outcomes for patients with ICH. However, the mechanisms responsible for this relationship remain poorly characterized. Thus, this study was designed to further explore the development and progression of hydrocephalus after secondary IVH. METHODS: Autologous blood injection model was induced to mimic ICH with ventricular extension (ICH/IVH) or primary IVH in Sprague-Dawley rats. Magnetic resonance imaging, Morris water maze, brain water content, Evans blue extravasation, immunohistochemistry staining, Western blot, iron determination, and electron microscopy were used in these rats. Then, deferoxamine treatment was used to clarify the involvement of iron in the development of hydrocephalus. RESULTS: Despite the injection of equivalent blood volumes, ICH/IVH resulted in more significant ventricular dilation, ependymal cilia damage, and iron overload, as well as more severe early brain injury and neurological deficits compared with IVH alone. Systemic deferoxamine treatment more effectively reduced ventricular enlargement in ICH/IVH compared with primary IVH. CONCLUSIONS: Our results show that ICH/IVH caused more significant chronic hydrocephalus and iron accumulation than primary IVH alone. Intracerebral hematoma plays a vital role in persistent iron overload and aggravated hydrocephalus after ICH/IVH. PMID- 26265130 TI - Routing Ambulances to Designated Centers Increases Access to Stroke Center Care and Enrollment in Prehospital Research. AB - BACKGROUND AND PURPOSE: Emergency medical services routing of patients with acute stroke to designated centers may increase the proportion of patients receiving care at facilities meeting national standards and augment recruitment for prehospital stroke research. METHODS: We analyzed consecutive patients enrolled within 2 hours of symptom onset in a prehospital stroke trial, before and after regional Los Angeles County Emergency Medical Services implementation of preferentially routing patients with acute stroke to approved stroke centers (ASCs). From January 2005 to mid-November 2009, patients were transported to the nearest emergency department, whereas from mid-November 2009 to December 2012, patients were preferentially transported to first 9, and eventually 29, ASCs. RESULTS: There were 863 subjects enrolled before and 764 after emergency medical service preferential routing, with implementation leading to an increase in the proportion cared for at an ASC from 10% to 91% (P<0.0001), with a slight decrease in paramedic on-scene to emergency department arrival time (34.5 [SD, 9.1] minutes versus 33.5 [SD, 10.3] minutes; P=0.045). The effects of routing were immediate and included an increase in proportion of receiving ASC care (from 17% to 88%; P<0.001) and a greater number of enrollments (18.6% increase) when comparing 12 months before and after regional stroke system implementation. CONCLUSIONS: The establishment of a regionalized emergency medical services system of acute stroke care dramatically increased the proportion of patients with acute stroke cared for at ASCs, from 1 in 10 to >9 in 10, with no clinically significant increase in prehospital care times and enhanced recruitment of patients into a prehospital treatment trial. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059332. PMID- 26265131 TI - Robot-assisted hepatic mobilization and control of suprahepatic infradiaphragmatic inferior vena cava for level 3 vena caval thrombectomy: An IDEAL stage 0 study. AB - Robot-assisted level 1/2 inferior vena caval (IVC) thrombectomy techniques have been recently described for clinical use. Following the IDEAL recommendations on safe surgical innovation, we here describe a robotic approach for level 3 IVC thrombectomy in fresh frozen cadavers (IDEAL stage 0). In all cadavers (n = 3), hepatic mobilization with control of short hepatic veins, contralateral renal vein, infrarenal IVC and suprahepatic-infradiaphragmatic IVC could be achieved successfully, without converting to open surgery. Clinical feasibility of our technique remains to be tested. PMID- 26265133 TI - Therapeutic drug monitoring of monoclonal antibodies in inflammatory and malignant disease: Translating TNF-alpha experience to oncology. AB - Lack of response to monoclonal antibodies (mAbs) has been associated with inadequate mAb serum concentrations. Therapeutic drug monitoring (TDM) of mAbs has the potential to guide to more effective dosing in individual patients. This review discusses the mechanisms responsible for interpatient variability of mAb pharmacokinetics, summarizes exposure-response data of mAbs used in inflammatory and malignant disease, presents current evidence of mAb-TDM in inflammatory disease, and provides hurdles and required future steps for further implementing mAb-TDM. PMID- 26265132 TI - Integrated analyses of zebrafish miRNA and mRNA expression profiles identify miR 29b and miR-223 as potential regulators of optic nerve regeneration. AB - BACKGROUND: Unlike mammals, zebrafish have the ability to regenerate damaged parts of their central nervous system (CNS) and regain functionality of the affected area. A better understanding of the molecular mechanisms involved in zebrafish regeneration may therefore provide insight into how CNS repair might be induced in mammals. Although many studies have described differences in gene expression in zebrafish during CNS regeneration, the regulatory mechanisms underpinning the differential expression of these genes have not been examined. RESULTS: We used microarrays to analyse and integrate the mRNA and microRNA (miRNA) expression profiles of zebrafish retina after optic nerve crush to identify potential regulatory mechanisms that underpin central nerve regeneration. Bioinformatic analysis identified 3 miRNAs and 657 mRNAs that were differentially expressed after injury. We then combined inverse correlations between our miRNA expression and mRNA expression, and integrated these findings with target predictions from TargetScan Fish to identify putative miRNA-gene target pairs. We focused on two over-expressed miRNAs (miR-29b and miR-223), and functionally validated seven of their predicted gene targets using RT-qPCR and luciferase assays to confirm miRNA-mRNA binding. Gene ontology analysis placed the miRNA-regulated genes (eva1a, layna, nefmb, ina, si:ch211-51a6.2, smoc1, sb:cb252) in key biological processes that included cell survival/apoptosis, ECM cytoskeleton signaling, and heparan sulfate proteoglycan binding, CONCLUSION: Our results suggest a key role for miR-29b and miR-223 in zebrafish regeneration. The identification of miRNA regulation in a zebrafish injury model provides a framework for future studies in which to investigate not only the cellular processes required for CNS regeneration, but also how these mechanisms might be regulated to promote successful repair and return of function in the injured mammalian brain. PMID- 26265134 TI - Differential requirements for H/ACA ribonucleoprotein components in cell proliferation and response to DNA damage. AB - H/ACA ribonucleoproteins (RNPs) are comprised of four conserved proteins, dyskerin, NHP2, NOP10, and GAR1, and a function-specifying, noncoding H/ACA RNA. H/ACA RNPs contribute to telomerase assembly and stabilization, and posttranscriptional processing of nascent ribosomal RNA and spliceosomal RNA. However, very little is known about the coordinated action of the four proteins in other biologic processes. As described herein, we observed a differential requirement for the proteins in cell proliferation and identified a possible reliance for these factors in regulation of specific DNA damage biomarkers. In particular, GAR1 expression was upregulated following exposure to all forms of genotoxic stress tested. In contrast, levels of the other proteins were either reduced or unaffected. Only GAR1 showed an altered subcellular localization with a shift from the nucleolus to the nucleoplasm after ultraviolet-C irradiation and doxorubicin treatments. Transient siRNA-mediated depletion of GAR1 and dyskerin arrested cell proliferation, whereas loss of either NHP2 or NOP10 had no effect. Finally, loss of dyskerin, GAR1, NHP2, and NOP10, respectively, limited the accumulation of DNA damage biomarkers. However, the individual responses were dependent upon the specific type of damage incurred. In general, loss of GAR1 had the most suppressive effect on the biomarkers tested. Since the specific responses to genotoxic stress, the contribution of each protein to cell proliferation, and the activation of DNA damage biomarkers were not equivalent, this suggests the possibility that at least some of the proteins, most notably GAR1, may potentially function independently of their respective roles within H/ACA RNP complexes. PMID- 26265135 TI - Predicting paclitaxel-induced neutropenia using the DMET platform. AB - AIM: The use of paclitaxel in cancer treatment is limited by paclitaxel-induced neutropenia. We investigated the ability of genetic variation in drug metabolizing enzymes and transporters to predict hematological toxicity. PATIENTS & METHODS: Using a discovery and validation approach, we identified a pharmacogenetic predictive model for neutropenia. For this, a drug-metabolizing enzymes and transporters plus DNA chip was used, which contains 1936 SNPs in 225 metabolic enzyme and drug-transporter genes. RESULTS: Our 10-SNP model in 279 paclitaxel-dosed patients reached 43% sensitivity in the validation cohort. Analysis in 3-weekly treated patients only resulted in improved sensitivity of 79%, with a specificity of 33%. None of our models reached statistical significance. CONCLUSION: Our drug-metabolizing enzymes and transporters-based SNP-models are currently of limited value for predicting paclitaxel-induced neutropenia in clinical practice. Original submitted 9 March 2015; Revision submitted 20 May 2015. PMID- 26265136 TI - Van der Waals Effects on semiconductor clusters. AB - Van der Waals (vdW) interactions play an important role on semiconductors in nanoscale. Here, we utilized first-principles calculations based on density functional theory to demonstrate the growth mode transition from prolate to multiunit configurations for Gen (n = 10-50) clusters. In agreement with the injected ion drift tube techniques that "clusters with n < 70 can be thought of as loosely bound assemblies of small strongly bound fragments (such as Ge7 and Ge10 )," we found these stable fragments are connected by Ge6 , Ge9 , or Ge10 unit (from bulk diamond), via strong covalent bonds. Our calculated cations usually fragment to Ge7 and Ge10 clusters, in accordance with the experiment results that the spectra Ge7 and Ge10 correspond to the mass abundance spectra. By controlling a germanium cluster with vdW interactions parameters in the program or not, we found that the vdW effects strengthen the covalent bond from different units more strikingly than that in a single unit. With more bonds between units than the threadlike structures, the multiunit structures have larger vdW energies, explaining why the isolated nanowires are harder to produce. (c) 2015 Wiley Periodicals, Inc. PMID- 26265137 TI - Intrinsic network connectivity abnormalities in HIV-infected individuals over age 60. AB - Individuals infected with HIV are living longer due to effective treatment with combination antiretroviral therapy (cART). Despite these advances, HIV-associated neurocognitive disorders (HAND) remain prevalent. In this study, we analyzed resting state functional connectivity (rs-fc) data from HIV-infected and matched HIV-uninfected adults aged 60 years and older to determine associations between HIV status, neuropsychological performance, and clinical variables. HIV-infected participants with detectable plasma HIV RNA exhibited decreased rs-fc within the salience (SAL) network compared to HIV-infected participants with suppressed plasma HIV RNA. We did not identify differences in rs-fc within HIV-infected individuals by HAND status. Our analysis identifies focal deficits in the SAL network that may be mitigated with suppression of plasma virus. However, these findings suggest that rs-fc may not be sensitive as a marker of HAND among individuals with suppressed plasma viral loads. PMID- 26265139 TI - UBXN2A regulates nicotinic receptor degradation by modulating the E3 ligase activity of CHIP. AB - Neuronal nicotinic acetylcholine receptors (nAChRs) containing the alpha3 subunit are known for their prominent role in normal ganglionic transmission while their involvement in the mechanisms underlying nicotine addiction and smoking-related disease has been emerging only in recent years. The amount of information available on the maturation and trafficking of alpha3-containing nAChRs is limited. We previously showed that UBXN2A is a p97 adaptor protein that facilitates the maturation and trafficking of alpha3-containing nAChRs. Further investigation of the mechanisms of UBXN2A actions revealed that the protein interacts with CHIP (carboxyl terminus of Hsc70 interacting protein), whose ubiquitin E3 ligase activity regulates the degradation of several disease-related proteins. We show that CHIP displays E3 ligase activity toward the alpha3 nAChR subunit and contributes to its ubiquitination and subsequent degradation. UBXN2A interferes with CHIP-mediated ubiquitination of alpha3 and protects the nicotinic receptor subunit from endoplasmic reticulum associated degradation (ERAD). UBXN2A also cross-talks with VCP/p97 and HSC70/HSP70 proteins in a complex where alpha3 is likely to be targeted by CHIP. Overall,we identify CHIP as an E3 ligase for alpha3 and UBXN2A as a protein that may efficiently regulate the stability of CHIP's client substrates. PMID- 26265138 TI - New paradigms in GPCR drug discovery. AB - G protein-coupled receptors (GPCRs) remain a major domain of pharmaceutical discovery. The identification of GPCR lead compounds and their optimization are now structure-based, thanks to advances in X-ray crystallography, molecular modeling, protein engineering and biophysical techniques. In silico screening provides useful hit molecules. New pharmacological approaches to tuning the pleotropic action of GPCRs include: allosteric modulators, biased ligands, GPCR heterodimer-targeted compounds, manipulation of polypharmacology, receptor antibodies and tailoring of drug molecules to fit GPCR pharmacogenomics. Measurements of kinetics and drug efficacy are factors influencing clinical success. With the exception of inhibitors of GPCR kinases, targeting of intracellular GPCR signaling or receptor cycling for therapeutic purposes remains a futuristic concept. New assay approaches are more efficient and multidimensional: cell-based, label-free, fluorescence-based assays, and biosensors. Tailoring GPCR drugs to a patient's genetic background is now being considered. Chemoinformatic tools can predict ADME-tox properties. New imaging technology visualizes drug action in vivo. Thus, there is reason to be optimistic that new technology for GPCR ligand discovery will help reverse the current narrowing of the pharmaceutical pipeline. PMID- 26265140 TI - Connexin 43-targeted T1 contrast agent for MRI diagnosis of glioma. AB - Glioblastoma multiforme is the most aggressive form of brain tumor. Early and accurate diagnosis of glioma and its borders is an important step for its successful treatment. One of the promising targets for selective visualization of glioma and its margins is connexin 43 (Cx43), which is highly expressed in reactive astrocytes and migrating glioma cells. The purpose of this study was to synthesize a Gd-based contrast agent conjugated with specific antibodies to Cx43 for efficient visualization of glioma C6 in vivo. We have prepared stable nontoxic conjugates of monoclonal antibody to Cx43 and polylysine-DTPA ligands complexed with Gd(III), which are characterized by higher T1 relaxivity (6.5 mM( 1) s(-1) at 7 T) than the commercial agent Magnevist(r) (3.4 mM(-1) s(-1)). Cellular uptake of Cx43-specific T1 contrast agent in glioma C6 cells was more than four times higher than the nonspecific IgG-contrast agent, as detected by flow cytometry and confocal analysis. MRI experiments showed that the obtained agents could markedly enhance visualization of glioma C6 in vivo after their intravenous administration. Significant accumulation of Cx43-targeted contrast agents in glioma and the peritumoral zone led not only to enhanced contrast but also to improved detection of the tumor periphery. Fluorescence imaging confirmed notable accumulation of Cx43-specific conjugates in the peritumoral zone compared with nonspecific IgG conjugates at 24 h after intravenous injection. All these features of Cx43-targeted contrast agents might be useful for more precise diagnosis of glioma and its borders by MRI. PMID- 26265141 TI - Evidence for protective effect of lipoic acid and desvenlafaxine on oxidative stress in a model depression in mice. AB - Oxidative stress is implicated in the neurobiology of depression. Here we investigated oxidative alterations in brain areas of animals submitted to the model of depression induced by corticosterone (CORT) and the effects of the antioxidant compound alpha-lipoic acid (ALA) alone or associated with the antidepressant desvenlafaxine (DVS) in these alterations. Female mice received vehicle or CORT (20 mg/kg) during 14 days. From the 15th to 21st days different animals received further administrations of: vehicle, DVS (10 or 20 mg/kg), ALA (100 or 200 mg/kg), or the combinations of DVS10+ALA100, DVS20+ALA100, DVS10+ALA200, or DVS20+ALA200. Twenty-four hours after the last drug administration prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) were dissected for the determination of the activity of superoxide dismutase (SOD), reduced glutathione (GSH) and lipid peroxidation (LP) levels. CORT significantly increased SOD activity in the PFC and HC, decreased GSH levels in the HC and increased LP in all brain areas studied when compared to saline-treated animals. Decrements of SOD activity were observed in all groups and brain areas studied when compared to controls and CORT. The hippocampal decrease in GSH was reversed by ALA100, DVS10+ALA100, DVS20+ALA100 and DVS20+ALA200. The same DVS+ALA combination groups presented increased levels of GSH in the PFC and ST. The greater GSH levels were observed in the PFC, HC and ST of DVS20+ALA200 mice. LP was reversed in the groups ALA200 (PFC), DVS10+ALA100, DVS20+ALA100 (PFC, HC and ST), and DVS20+ALA200 (PFC, HC). Our findings contribute to the previous preclinical evidences implicating ALA as a promising agent for augmentation therapy in depression. PMID- 26265143 TI - Effect of maternal and treatment-related factors on the prevalence of birth defects after PESA-ICSI and TESE-ICSI: a retrospective cohort study. AB - INTRODUCTION: We performed a retrospective cohort study with the aim to evaluate the effect of maternal and treatment-related factors on the prevalence of birth defects after intracytoplasmic sperm injection (ICSI) using percutaneous epididymal sperm aspiration (PESA) and testicular sperm extraction (TESE). MATERIAL AND METHODS: 643 newborns born after PESA-ICSI (n = 406) and TESE-ICSI (n = 237) in Radboud University Medical Center, after a gestational age of 12 weeks, 1 January 2002-1 January 2011 and 1 March-1 November 2014, respectively, were included in this study. Three sources of data were used for analysis: questionnaires, national obstetrics registration forms, and a lab-database of all ICSI treatments. Data were analyzed using generalized estimating equations and logistic regression analysis. RESULTS: The prevalence of major birth defects in newborns born after PESA-ICSI was 6.9% and after TESE-ICSI was 5.9% (odds ratio 0.89, 95% confidence interval 0.46-1.75). No significant association was found between maternal or treatment-related factors and the prevalence of birth defects. CONCLUSIONS: We found a similar overall prevalence of birth defects in newborns born after PESA-ICSI and TESE-ICSI. The maternal and treatment-related factors investigated did not show a significantly increased cumulative risk of birth defects. PMID- 26265142 TI - Decoding breast cancer tissue-stroma interactions using species-specific sequencing. AB - INTRODUCTION: Decoding transcriptional effects of experimental tissue-tissue or cell-cell interactions is important; for example, to better understand tumor stroma interactions after transplantation of human cells into mouse (xenografting). Transcriptome analysis of intermixed human and mouse cells has, however, frequently relied on the need to separate the two cell populations prior to transcriptome analysis, which introduces confounding effects on gene expression. METHODS: To circumvent this problem, we here describe a bioinformatics-based, genome-wide transcriptome analysis technique, which allows the human and mouse transcriptomes to be decoded from a mixed mouse and human cell population. The technique is based on a bioinformatic separation of the mouse and human transcriptomes from the initial mixed-species transcriptome resulting from sequencing an excised tumor/stroma specimen without prior cell sorting. RESULTS: Under stringent separation criteria, i.e., with a read misassignment frequency of 0.2 %, we show that 99 % of the genes can successfully be assigned to be of mouse or human origin, both in silico, in cultured cells and in vivo. We use a new species-specific sequencing technology-referred to as S(3) ("S-cube")-to provide new insights into the Notch downstream response following Notch ligand-stimulation and to explore transcriptional changes following transplantation of two different breast cancer cell lines (luminal MCF7 and basal type MDA-MB-231) into mammary fat pad tissue in mice of different immunological status. We find that MCF7 and MDA-MB-231 respond differently to fat pad xenografting and the stromal response to transplantation of MCF7 and MDA-MB-231 cells was also distinct. CONCLUSIONS: In conclusion, the data show that the S(3) technology allows for faithful recording of transcriptomic changes when human and mouse cells are intermixed and that it can be applied to address a broad spectrum of research questions. PMID- 26265144 TI - The long non-coding RNA world in yeasts. AB - In recent years, it has become evident that eukaryotic genomes are pervasively transcribed and produce numerous non-coding transcripts, including long non coding RNAs (lncRNAs). Although research of such genomic enigmas is in the early stages, a growing number of lncRNAs have been characterized and found to be principal actors in a variety of biological processes rather than merely representing transcriptional noise. Here, we review recent findings on lncRNAs in yeast systems. We especially focus on lncRNA-mediated cellular regulations to respond to environmental changes in the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa. PMID- 26265145 TI - Methods for distinguishing between protein-coding and long noncoding RNAs and the elusive biological purpose of translation of long noncoding RNAs. AB - Long noncoding RNAs (lncRNAs) are a diverse class of RNAs with increasingly appreciated functions in vertebrates, yet much of their biology remains poorly understood. In particular, it is unclear to what extent the current catalog of over 10,000 annotated lncRNAs is indeed devoid of genes coding for proteins. Here we review the available computational and experimental schemes for distinguishing between coding and noncoding transcripts and assess the conclusions from their recent genome-wide applications. We conclude that the model most consistent with the available data is that a large number of mammalian lncRNAs undergo translation, but only a very small minority of such translation events results in stable and functional peptides. The outcomes of the majority of the translation events and their potential biological purposes remain an intriguing topic for future investigation. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa. PMID- 26265146 TI - Development of an in vivo tissue-engineered vascular graft with designed wall thickness (biotube type C) based on a novel caged mold. AB - Small-diameter biotube vascular grafts developed by in-body tissue architecture had high patency at implantation into rabbit carotid arteries or rat abdominal aortas. However, the thin walls (34 +/- 14 MUm) of the original biotubes made their implantation difficult into areas with low blood flow volumes or low blood pressure due to insufficient mechanical strength to maintain luminal shape. In this study, caged molds with several windows were designed to prepare more robust biotubes. The molds were assembled with silicone tubes (external diameter 2 mm) and cylindrical covers (outer diameter 7 mm) with 12 linear windows (1 * 9 mm). After the molds were embedded into beagle dorsal subcutaneous pouches for 4 weeks, type C (cage) biotubes were obtained by completely extracting the surrounding connective tissues from the molds and removing the molds. The biotube walls (778 +/- 31 MUm) were formed at the aperture (width 1 mm) between the silicone rods and the covers by connective cell migration through the windows of the covers. Excellent mechanical properties (external pressure resistance, approximately 4 times higher than beagle native femoral arteries; burst strength, approximately 2 times higher than original biotubes) were obtained. In the acute phase of implantation of the biotubes into beagle femoral arteries, perfect patency was obtained with little stenosis and no aneurysmal dilation. The type C biotubes may be useful for implantation into peripheral arteries or veins in addition to aortas. PMID- 26265147 TI - Post hoc interlaboratory comparison of single particle ICP-MS size measurements of NIST gold nanoparticle reference materials. AB - Single particle inductively coupled plasma-mass spectrometry (spICP-MS) is an emerging technique that enables simultaneous measurement of nanoparticle size and number quantification of metal-containing nanoparticles at realistic environmental exposure concentrations. Such measurements are needed to understand the potential environmental and human health risks of nanoparticles. Before spICP MS can be considered a mature methodology, additional work is needed to standardize this technique including an assessment of the reliability and variability of size distribution measurements and the transferability of the technique among laboratories. This paper presents the first post hoc interlaboratory comparison study of the spICP-MS technique. Measurement results provided by six expert laboratories for two National Institute of Standards and Technology (NIST) gold nanoparticle reference materials (RM 8012 and RM 8013) were employed. The general agreement in particle size between spICP-MS measurements and measurements by six reference techniques demonstrates the reliability of spICP-MS and validates its sizing capability. However, the precision of the spICP-MS measurement was better for the larger 60 nm gold nanoparticles and evaluation of spICP-MS precision indicates substantial variability among laboratories, with lower variability between operators within laboratories. Global particle number concentration and Au mass concentration recovery were quantitative for RM 8013 but significantly lower and with a greater variability for RM 8012. Statistical analysis did not suggest an optimal dwell time, because this parameter did not significantly affect either the measured mean particle size or the ability to count nanoparticles. Finally, the spICP-MS data were often best fit with several single non-Gaussian distributions or mixtures of Gaussian distributions, rather than the more frequently used normal or log-normal distributions. PMID- 26265148 TI - Client/patient perceptions of achieving equity in primary health care: a mixed methods study. AB - INTRODUCTION: To provide health care on equal terms has become a challenge for the health system. As the front line in health services, primary care has a key role to play in developing equitable health care, responsive to the needs of different population groups. Reducing inequalities in care has been a central and recurring theme in Swedish health reforms. The aim of this study is to describe and assess client/patient experiences and perceptions of care in four primary health care units (PHCUs) involved in Sweden's national Care on Equal Terms project. METHODS: Mixed Method Research (MMR) was chosen to describe and assess client/patient experiences and perceptions of health care with regard to equity. There was a focus group discussion, and individual interviews with 21 clients/patients and three representatives of patient associations. Data from the Swedish National Patient Survey (NPS), conducted in 2011 and followed up in 2013, were also used. RESULTS: The interview data were divided into two main categories and three subcategories. The first category "Perception of equitable health care" had two subcategories, namely "Health care providers' perceptions" and "Fairness and participation". The second category "To achieve more equitable health care" had four subcategories: "Encounter", "Access", "Interpreters and bilingual/diverse health care providers" and "Time pressure and continuity". Results from the NPS showed that two of the PHCUs improved in some aspects of patient perceived quality of care (PPQC) while two were not so successful. CONCLUSIONS: Clients/patients perceived health care providers' perceptions of their ethnic origin and mental health status as important for equitable health care. Discriminatory perceptions may lead to those in need of care refraining from seeking it. More equitable care means longer consultations, better accessibility in terms of longer opening hours, and ways of communicating other than just via voice mail. It also involves continuity in care and access to an interpreter if needed. Employing bilingual/diverse kinds of health providers is a way of providing more equitable primary health care. PMID- 26265149 TI - Socio-cultural factors, gender roles and religious ideologies contributing to Caesarian-section refusal in Nigeria. AB - BACKGROUND: The death of women from pregnancy-related causes is a serious challenge that international development initiatives, including the Millennium Development Goals, have been trying to redress for decades. The majority of these pregnancy-related deaths occur in developing countries especially in Sub-Saharan Africa. The provision of Emergency Obstetric Care (EmOC), including Caesarean section (CS) has been identified as one of the key ingredients necessary for the reduction of high maternal mortality ratios. However, it appears that creating access to EmOC facilities is not all that is required to reduce maternal mortality: socio-cultural issues in Sub-Saharan countries including Nigeria seem to deter women from accepting CS. This study seeks to explore some of the socio cultural concerns that reinforce delays and non-acceptance of CS in a Nigerian community. METHODS: This is a mixed method study that combined both qualitative and quantitative strategies of enquiry. The hospital's delivery records from 2006 2010 provided data for quantitative analysis. This quantitative data was supplemented with prospective data collected during one month. Semi-structured interviews, focus group discussions (FGD) and informal observations served as the sources of data on the qualitative end. RESULTS: In total, 22% of maternity clients refused CS and more than 90% of the CSs in the focal hospital were emergencies which may indicate late arrival at the hospital after seeking assistance elsewhere. The qualitative analysis reveals that socio-cultural meanings informed by gender and religious ideologies, the relational consequences of having a C-section, and the role of alternative providers are some key factors which influence when, where and whether women will accept C-section or not. CONCLUSION: There is need to find means of facilitating necessary CS by addressing the prevailing socio-cultural norms and expectations that hinder its acceptance. Engaging and guiding alternative providers (traditional birth attendants and faith healers) who wield much power in their communities, will be important to minimize delays and improve cultural acceptability of CS. PMID- 26265150 TI - Prediction of the filter no-reflow phenomenon in patients with angina pectoris by using multimodality: Magnetic resonance imaging, optical coherence tomography, and serum biomarkers. AB - BACKGROUND: Although the occurrence of no-reflow during percutaneous coronary intervention (PCI) has been shown to be associated with worse short- and long term clinical outcomes, the clinical relevance of preventing flow deterioration by using the filter-based distal protection devices (DPDs) is controversial. We investigated predictors of the filter no-reflow (FNR) phenomenon during PCI by using multimodality, such as hyperintense plaques (HIPs) in the coronary artery on T1-weighted imaging (T1WI) non-contrast magnetic resonance, plaque composition by using optical coherence tomography (OCT), and serum biomarkers, in patients with angina pectoris. METHODS AND RESULTS: Fifty lesions from 50 patients with angina were examined. All patients underwent T1WI within 24 h before invasive coronary angiography was performed, and preinterventional OCT was performed on a native atherosclerotic culprit lesion. The signal intensity of coronary plaque to cardiac muscle ratio (PMR) was calculated on a standard console of the magnetic resonance system. Of the 50 lesions, 20 lesions showed FNR during PCI, while non FNR was observed in 30 lesions. A cut-off value >1.85 of PMR had a sensitivity of 65%, a specificity of 93%, a positive predictive value of 87%, and a negative predictive value of 80% for identifying lesions with FNR. Multivariate analysis revealed that the presence of HIPs with PMR >1.85 (p=0.008) was the only independent predictor of the FNR phenomenon during PCI. CONCLUSIONS: This study shows that the presence of HIPs with PMR >1.85 on T1WI was a novel independent predictor of the FNR phenomenon during PCI in angina patients. This result may help in identifying high-risk lesions for no-reflow to deploy filter-based DPDs. PMID- 26265151 TI - Author's reply. PMID- 26265152 TI - Increasing incidence of rotator cuff repairs--A nationwide registry study in Finland. AB - BACKGROUND: Rotator cuff repair incidence rates have reportedly increased in the United States and England. Here we analyzed nationwide data relating to rotator cuff repairs recorded in the Finnish National Hospital Discharge Register (NHDR). METHODS: The NHDR was reviewed to identify adult patients who underwent rotator cuff repair between 1998 and 2011. Incidence rates per 10(5) person-years were calculated using the annual adult population size. RESULTS: During the 14-year time period, 50,646 rotator cuff repairs were performed on subjects aged 18 years or older. The incidence of rotator cuff repair showed an almost linear increase of 204%, from 44 per 10(5) person-years in 1998 to 131 per 10(5) person-years in 2011. The most common concomitant procedure was acromioplasty, which was performed in approximately 40% of rotator cuff repairs in 2011. Other common concomitant procedures included tenodesis (7%) and tenotomy (6%) of the long head of the biceps tendon, and resection of the acromioclavicular joint (3%). CONCLUSIONS: This nationwide analysis revealed a remarkable increase in the incidence of rotator cuff repair from 1998 to 2011 in Finland. This progress can be questioned, since there are not convincing data of the superiority of the operative treatment over non-operative management in all rotator cuff tears. PMID- 26265153 TI - The 5-lipoxygenase (5-LOX) Inhibitor Zileuton Reduces Inflammation and Infarct Size with Improvement in Neurological Outcome Following Cerebral Ischemia. AB - Stroke is one of the most frequent causes of death and disability worldwide causing a major clinical and socioeconomic impact. Although the pathophysiology of brain ischemia and reperfusion is complex, the inflammatory process plays an important role in pathogenesis, contributing to the expansion of brain injury. The 5-lipoxygenase (5-LOX) is a key enzyme in the biosynthesis of the leukotrienes and has been implicated and in the central nervous system (CNS) disorders such as Alzheimer's disease and acute ischemic stroke. Zileuton, a selective 5-LOX inhibitor, has antiinflammatory properties and exerts an inhibitory effect on inflammatory diseases. The objective of this study was to evaluate the effects of blocking 5-LOX activity in a murine model of transient and global brain ischemia. Zileuton improved neurological deficits and significantly decrease volume and density of lesion, compared to vehicle-ischemic animals measured by magnetic resonance imaging (MRI). In addition, the blockage of 5-LOX reduced infarct area and histopathological changes. Furthermore, by enzyme immunoassay (ELISA) increased brain levels of tumor necrosis factor-alpha (TNFalpha), interferon-gamma (IFN-gamma), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C-C motif) ligand 3 (CCL3) and chemokine (C-C motif) ligand 5 (CCL5) were detected in the vehicle-ischemic group, whereas in Zileuton-ischemic group presented reduction of these mediators. The concentration of the antiinflammatory cytokine interleukin-10 (IL-10) was increased after 5-LOX inhibition. Our results suggest that Zileuton decreases brain damage and reduces inflammatory cytokines expression in the CNS which contributes, at least in part, to improve the neurological outcome of brain ischemia. PMID- 26265154 TI - Curcumin, Hesperidin, and Rutin Selectively Interfere with Apoptosis Signaling and Attenuate Streptozotocin-Induced Oxidative Stress-Mediated Hyperglycemia. AB - Type I Diabetes is characterized by the presence of hyperglycemia due to insulin deficiency and consequent impaired hepatic glucose metabolism. During diabetes, the liver becomes the most important tissue for the regulation of serum glucose. However, elevated glucose causes continuous oxidative damage to the liver, reducing its capacity to ameliorate hyperglycemia, which contributes to macrovascular complications [1]. Numerous epidemiological studies have demonstrated that excess human consumption of diets rich in specific bioflavonoid phytochemicals attenuates the effects of diabetes. Thus, this study was designed to investigate whether a bioflavonoid mixture could : i) attenuate streptozotocin (STZ)-induced hyperglycemia, ii) potentiate antioxidant signaling in the liver, and iii) ameliorate the apoptotic signaling cascade in the liver of STZ-induced hyperglycemic mice. In order to examine our hypothesis, three well-investigated antioxidant phytochemicals, curcumin, hesperidin and rutin, were combined into a mixture (CHR) for this study. Diabetes was induced in 6-month-old female ICR mice by STZ (100 mg/kg, i.p.) administration, and CHR or vehicle control was orally administered (200 mg/kg per body weight of each ingredient) to the hyperglycemic mice (blood glucose levels > 250 mg/dl) for a period of 14 days. Administration of CHR to the hyperglycemic mice significantly reduced blood glucose levels, attenuated STZ-induced lipid peroxidation and total nitrate/nitrite levels, and significantly augmented the expression of superoxide dismutase and glutathione in the liver. STZ-induced hyperglycemia resulted in downregulation of antiapoptotic proteins Bcl-2 by 66% and Bcl-XL by 51%, and upregulation of the pro-apoptotic Bad (69%) with an increase in the ratio of cytosolic/mitochondrial cytochrome c by 81% in hepatic tissue. Administration of CHR significantly ameliorated apoptotic signaling in STZ-induced diabetic mice, significantly increasing Bad/Bcl-2 and Bad/Bcl-XL ratios to 410% and 244% respectively in the hyperglycemic group. This study demonstrated that a bioflavonoid mixture of curcumin, hesperidin and rutin (CHR) ameliorates hepatic oxidative stress caused by STZ-induced hyperglycemia, resulting in improved hepatic function and glucose regulation. PMID- 26265155 TI - Fast analysis of 29 polycyclic aromatic hydrocarbons (PAHs) and nitro-PAHs with ultra-high performance liquid chromatography-atmospheric pressure photoionization tandem mass spectrometry. AB - Polycyclic aromatic hydrocarbons (PAHs) and nitro-PAHs are ubiquitous in the environment. Some of them are probable carcinogens and some are source markers. This work presents an ultra-high performance liquid chromatography-atmospheric pressure photoionization-tandem mass spectrometry (UHPLC-APPI-MS/MS) method for simultaneous analysis of 20 PAHs and nine nitro-PAHs. These compounds are separated in 15 minutes in the positive mode and 11 minutes in the negative mode, one half of GC/MS analysis time. Two pairs of precursor/product ions are offered, which is essential for confirmation. This method separates and quantifies benzo[a]pyrene (the most toxic PAHs) and non-priority benzo[e]pyrene (isomers, little toxicity) to avoid overestimation of toxin levels, demonstrating its importance for health-related researches. With 0.5% 2,4-difluoroanisole in chlorobenzene as the dopant, limits of detection of PAHs except acenaphthylene and those of nitro-PAHs except 2-nitrofluoranthene are below 10 pg and 3 pg, respectively, mostly lower than or comparable to those reported using LC-related systems. The responses were linear over two orders of magnitude with fairly good accuracy and precision. Certified reference materials and real aerosol samples were analyzed to demonstrate its applicability. This fast, sensitive, and reliable method is the first UHPLC-APPI-MS/MS method capable of simultaneously analyzing 29 environmentally and toxicologically important PAHs and nitro-PAHs. PMID- 26265156 TI - Neural valuation of environmental resources. AB - How do people value environmental resources? To estimate public valuation of natural resources, researchers often conduct surveys that ask people how much they would be willing to pay to preserve or restore threatened natural resources. However, these survey responses often elicit complex affective responses, including negative reactions toward proposed destructive land uses of those resources. To better characterize processes that underlie the valuation of environmental resources, we conducted behavioral and neuroimaging experiments in which subjects chose whether or not to donate money to protect natural park lands (iconic versus non-iconic) from proposed land uses (destructive versus non destructive). In both studies, land use destructiveness motivated subjects' donations more powerfully than did the iconic qualities of the parks themselves. Consistent with an anticipatory affect account, nucleus accumbens (NAcc) activity increased in response to more iconic parks, while anterior insula activity increased in response to more destructive uses, and the interaction of these considerations altered activity in the medial prefrontal cortex (MPFC). Further, anterior insula activity predicted increased donations to preserve parks threatened by destructive uses, but MPFC activity predicted reduced donations. Finally, individuals with stronger pro-environmental attitudes showed greater anterior insula activity in response to proposed destructive uses. These results imply that negative responses to destructive land uses may play a prominent role in environmental valuation, potentially overshadowing positive responses to the environmental resources themselves. The findings also suggest that neuroimaging methods might eventually complement traditional survey methods by allowing researchers to disentangle distinct affective responses that influence environmental valuation. PMID- 26265158 TI - Monotonic non-linear transformations as a tool to investigate age-related effects on brain white matter integrity: A Box-Cox investigation. AB - Non-linear effects of age on white matter integrity are ubiquitous in the brain and indicate that these effects are more pronounced in certain brain regions at specific ages. Box-Cox analysis is a technique to increase the log-likelihood of linear relationships between variables by means of monotonic non-linear transformations. Here we employ Box-Cox transformations to flexibly and parsimoniously determine the degree of non-linearity of age-related effects on white matter integrity by means of model comparisons using a voxel-wise approach. Analysis of white matter integrity in a sample of adults between 20 and 89years of age (n=88) revealed that considerable portions of the white matter in the corpus callosum, cerebellum, pallidum, brainstem, superior occipito-frontal fascicle and optic radiation show non-linear effects of age. Global analyses revealed an increase in the average non-linearity from fractional anisotropy to radial diffusivity, axial diffusivity, and mean diffusivity. These results suggest that Box-Cox transformations are a useful and flexible tool to investigate more complex non-linear effects of age on white matter integrity and extend the functionality of the Box-Cox analysis in neuroimaging. PMID- 26265157 TI - Interactive effects of physical activity and APOE-epsilon4 on white matter tract diffusivity in healthy elders. AB - Older adult apolipoprotein-E epsilon 4 (APOE-epsilon4) allele carriers vary considerably in the expression of clinical symptoms of Alzheimer's disease (AD), suggesting that lifestyle or other factors may offer protection from AD-related neurodegeneration. We recently reported that physically active APOE-epsilon4 allele carriers exhibit a stable cognitive trajectory and protection from hippocampal atrophy over 18months compared to sedentary epsilon4 allele carriers. The aim of this study was to examine the interactions between genetic risk for AD and physical activity (PA) on white matter (WM) tract integrity, using diffusion tensor imaging (DTI) MRI, in this cohort of healthy older adults (ages of 65 to 89). Four groups were compared based on the presence or absence of an APOE epsilon4 allele (High Risk; Low Risk) and self-reported frequency and intensity of leisure time physical activity (PA) (High PA; Low PA). As predicted, greater levels of PA were associated with greater fractional anisotropy (FA) and lower radial diffusivity in healthy older adults who did not possess the APOE-epsilon4 allele. However, the effects of PA were reversed in older adults who were at increased genetic risk for AD, resulting in significant interactions between PA and genetic risk in several WM tracts. In the High Risk-Low PA participants, who had exhibited episodic memory decline over the previous 18-months, radial diffusivity was lower and fractional anisotropy was higher, compared to the High Risk-High PA participants. In WM tracts that subserve learning and memory processes, radial diffusivity (DR) was negatively correlated with episodic memory performance in physically inactive APOE-epsilon4 carriers, whereas DR was positively correlated with episodic memory performance in physically active APOE epsilon4 carriers and the two Low Risk groups. The common model of demyelination induced increase in radial diffusivity cannot directly explain these results. Rather, we hypothesize that PA may protect APOE-epsilon4 allele carriers from selective neurodegeneration of individual fiber populations at locations of crossing fibers within projection and association WM fiber tracts. PMID- 26265159 TI - Giant thymolipoma: A rare case presentation. AB - Thymolipoma is an unusual benign tumor of the mediastinum, comprising 2%-9% of thymic neoplasms. Most presentations are atypical. Here we present the case of a 68-year-old man with effort intolerance and fatigue for 4 months. Computed tomography of the chest revealed a lipomatous mass in the anterior mediastinum and bilateral hemithoraces. There were atelectatic changes in both lungs. The tumor was resected via a midline sternotomy. The patient had to be ventilated for 3 days postoperatively. The histopathological diagnosis was pleomorphic thymolipoma. PMID- 26265160 TI - Cancer patients' preferences of care within hospitals: a systematic literature review. AB - PURPOSE: Knowledge about cancer patients' preferences in health care is important because it enables care to be patient centered. However, the literature does not provide an overview. The aim of this study was to identify the dimensions of hospital-based cancer care that patients evaluate the most important using Patient-rated importance as a method. DATA SOURCE: PubMed was searched in 2013/2014. STUDY SELECTION: Studies were identified, if they were in accordance with specific search terms and focused on hospital-based cancer care. Totally, 11 studies were found. DATA EXTRACTION: The 11 studies comprised a total of 598 items. Of these, 592 items were categorized into 19 care dimensions. The highest rated quartile of items was identified as care elements patients evaluated to be the most important. Identification of the most important dimensions was done by calculating the percentages of items within each dimension that were within the highest quartile. RESULTS OF DATA SYNTHESIS: The 11 studies varied a lot in regard to aim and patient characteristics. The three most important dimensions were as follows: Rapid diagnosis and treatment; High professional standard; and Information about treatment and side(effects)/consequences. Within four dimensions, Psychosocial support, Physical facilities, Waiting time and Transparency in care, no items were within the highest quartile. CONCLUSION: Patient-rated importance was a useful method in identifying the care patients preferred. Due to a limited number of studies and great diversity within studies evaluated, interpretation of results should be cautious. However, it seems that cancer patients treated in hospitals with a curative intent find treatment related information, professional standard and short delay of diagnosis and treatment most important. PMID- 26265161 TI - Ethnic differences in help-seeking behaviour following child sexual abuse: a multi-method study. AB - In Western societies, groups from a minority ethnic background are under represented in formal mental health care. However, it is unknown if the minority ethnic victims of child sexual abuse differ from majority ethnic victims regarding their help-seeking behaviours. This study used a multi-method design to investigate the prevalence of (in) formal help-seeking after child sexual abuse and the influence of attitudes towards gender roles and sexuality on help-seeking among the Dutch minority ethnic and majority ethnic victims. We also examined differences in reasons not to seek help. Quantitative survey data on help-seeking patterns among 1496 child sexual abuse victims were collected. Four qualitative focus groups were conducted with professionals working in the field of child sexual abuse and minority ethnic groups to explore help-seeking behaviour. No significant differences between ethnicity emerged in help-seeking rates. However, respondents with more liberal gender attitudes were more likely to disclose than conservative respondents. Additionally, an interaction effect was observed between ethnicity and gender attitudes, indicating that, contrary to the main effect, young people of Moroccan and Turkish heritage with more liberal gender attitudes were less likely to disclose abuse. Reasons for not seeking help differed among groups. Focus group members emphasised mistrust towards counsellors and perceptions that inhibit minority ethnic youth from seeking help. PMID- 26265162 TI - Celebrating Soft Matter's 10th Anniversary: Cell division: a source of active stress in cellular monolayers. AB - We introduce the notion of cell division-induced activity and show that the cell division generates extensile forces and drives dynamical patterns in cell assemblies. Extending the hydrodynamic models of lyotropic active nematics we describe turbulent-like velocity fields that are generated by the cell division in a confluent monolayer of cells. We show that the experimentally measured flow field of dividing Madin-Darby Canine Kidney (MDCK) cells is reproduced by our modeling approach. Division-induced activity acts together with intrinsic activity of the cells in extensile and contractile cell assemblies to change the flow and director patterns and the density of topological defects. Finally we model the evolution of the boundary of a cellular colony and compare the fingering instabilities induced by cell division to experimental observations on the expansion of MDCK cell cultures. PMID- 26265163 TI - Linkage inversion assembled nano-aptasensors (LIANAs) for turn-on fluorescence detection. AB - A strategy for aptamer-based biosensing termed linkage inversion assembled nano aptasensors (LIANAs) is shown to be a generally applicable approach to the sensitive and specific detection of a target molecule in turn-on fluorescence solution-based and paper-based tests. PMID- 26265164 TI - Antiretroviral treatment use, co-morbidities and clinical outcomes among Aboriginal participants in the Australian HIV Observational Database (AHOD). AB - BACKGROUND: There are few data regarding clinical care and outcomes of Indigenous Australians living with HIV and it is unknown if these differ from non-Indigenous HIV-positive Australians. METHODS: AHOD commenced enrolment in 1999 and is a prospective cohort of HIV-positive participants attending HIV outpatient services throughout Australia, of which 20 (74 %) sites report Indigenous status. Data were collected up until March 2013 and compared between Indigenous and non Indigenous participants. Person-year methods were used to compare death rates, rates of loss to follow-up and rates of laboratory testing during follow-up between Indigenous and non-Indigenous participants. Factors associated with time to first combination antiretroviral therapy (cART) regimen change were assessed using Kaplan Meier and Cox Proportional hazards methods. RESULTS: Forty-two of 2197 (1.9 %) participants were Indigenous. Follow-up amongst Indigenous and non Indigenous participants was 332 & 16270 person-years, respectively. HIV virological suppression was achieved in similar proportions of Indigenous and non Indigenous participants 2 years after initiation of cART (81.0 % vs 76.5 %, p = 0.635). Indigenous status was not independently associated with shorter time to change from first- to second-line cART (aHR 0.95, 95 % CI 0.51-1.76, p = 0.957). Compared with non-Indigenous participants, Indigenous participants had significantly less frequent laboratory monitoring of CD4 count (rate:2.76 tests/year vs 2.97 tests/year, p = 0.025) and HIV viral load (rate:2.53 tests/year vs 2.93 tests/year, p < 0.001), while testing rates for lipids and blood glucose were almost half that of non-indigenous participants (rate:0.43/year vs 0.71 tests/year, p < 0.001). Loss to follow-up (23.8 % vs 29.8 %, p = 0.496) and death (2.4 % vs 7.1 %, p = 0.361) occurred in similar proportions of indigenous and non-Indigenous participants, respectively, although causes of death in both groups were mostly non-HIV-related. CONCLUSIONS: As far as we are aware, these are the first data comparing clinical outcomes between Indigenous and non-Indigenous HIV-positive Australians. The forty-two Indigenous participants represent over 10 % of all Indigenous Australians ever diagnosed with HIV. Although outcomes were not significantly different, Indigenous patients had lower rates of laboratory testing for HIV and lipid/glucose parameters. Given the elevated risk of cardiovascular disease in the general Indigenous community, the additional risk factor of HIV infection warrants further focus on modifiable risk factors to maximise life expectancy in this population. PMID- 26265165 TI - A chemistry and material perspective on lithium redox flow batteries towards high density electrical energy storage. AB - Electrical energy storage system such as secondary batteries is the principle power source for portable electronics, electric vehicles and stationary energy storage. As an emerging battery technology, Li-redox flow batteries inherit the advantageous features of modular design of conventional redox flow batteries and high voltage and energy efficiency of Li-ion batteries, showing great promise as efficient electrical energy storage system in transportation, commercial, and residential applications. The chemistry of lithium redox flow batteries with aqueous or non-aqueous electrolyte enables widened electrochemical potential window thus may provide much greater energy density and efficiency than conventional redox flow batteries based on proton chemistry. This Review summarizes the design rationale, fundamentals and characterization of Li-redox flow batteries from a chemistry and material perspective, with particular emphasis on the new chemistries and materials. The latest advances and associated challenges/opportunities are comprehensively discussed. PMID- 26265167 TI - Chronic fatigue in 812 testicular cancer survivors during long-term follow-up: increasing prevalence and risk factors. AB - BACKGROUND: Chronic fatigue (CF) has been reported to be slightly more prevalent in testicular cancer survivors (TCSs) than in the general population. In this study, we wished to explore possible determinants of CF in TCSs median 12 (survey I) and 19 years (survey II) after treatment, in particular the relation to late effects after treatment. PATIENTS AND METHODS: Overall, 812 TCSs treated between 1980 and 1994 provided blood samples (testosterone and luteinizing hormone) and completed questionnaires at survey I (1998-2002) and survey II (2007-2008). Hormone levels were categorized according to quartile thresholds for decadal age groups of controls. Associations between CF and possible risk factors, including the Hospital Anxiety and Depression Scale (HADS), treatment, physical activity, hormone levels, neurotoxicity, and comorbidity, were analyzed by logistic regression. RESULTS: Prevalence of CF increased from 15% at survey I to 27% at survey II (P < 0.001). At survey II, risk for CF was increased three- to four fold for high levels of neuropathy compared with no neuropathy, and two- to three fold for high levels of Raynaud-like phenomena, and having testosterone levels in the lowest quartile, while being moderately and highly physically active, had a protective effect. Risk for CF in TCSs with higher levels of HADS-Anxiety and HADS-Depression was increased two- to five-fold, respectively. CONCLUSIONS: The increasing prevalence of CF in TCSs is a novel finding. Lifestyle interventions, early detection and treatment of depression and anxiety, and possibly testosterone substitution might reduce the risk of CF. Extended long-term follow up seems to be important. PMID- 26265168 TI - Tivantinib added to erlotinib in nonsmall-cell lung cancer: the primary end point was not MET.... PMID- 26265169 TI - A real opportunity to improve neurology services in England. PMID- 26265166 TI - Mesenchymal stem/stromal cells as a delivery platform in cell and gene therapies. AB - Regenerative medicine relying on cell and gene therapies is one of the most promising approaches to repair tissues. Multipotent mesenchymal stem/stromal cells (MSC), a population of progenitors committing into mesoderm lineages, are progressively demonstrating therapeutic capabilities far beyond their differentiation capacities. The mechanisms by which MSC exert these actions include the release of biomolecules with anti-inflammatory, immunomodulating, anti-fibrogenic, and trophic functions. While we expect the spectra of these molecules with a therapeutic profile to progressively expand, several human pathological conditions have begun to benefit from these biomolecule-delivering properties. In addition, MSC have also been proposed to vehicle genes capable of further empowering these functions. This review deals with the therapeutic properties of MSC, focusing on their ability to secrete naturally produced or gene-induced factors that can be used in the treatment of kidney, lung, heart, liver, pancreas, nervous system, and skeletal diseases. We specifically focus on the different modalities by which MSC can exert these functions. We aim to provide an updated understanding of these paracrine mechanisms as a prerequisite to broadening the therapeutic potential and clinical impact of MSC. PMID- 26265170 TI - Complications Associated With Use of Long-Term Central Venous Catheters Among Commercially Insured Women With Breast Cancer. AB - PURPOSE: Despite some advantages to their use, long-term central venous catheters (CVCs) are associated with complications for patients who require chemotherapy. Understanding of these risks in commercially insured populations is limited. This information can inform medical policies that ensure the appropriate use of venous access devices. This study's objectives were to assess the extent of variation in use of long-term CVCs in a cohort of commercially insured women with breast cancer, and to assess risks of associated complications. METHODS: Retrospective cohort analysis was conducted using health insurance claims between January 2006 and October 2013. The cohort included commercially insured women age >= 18 years diagnosed with breast cancer who received infusion chemotherapy (N = 31,047). We conducted matched and case-mix adjusted Cox proportional hazard modeling to assess differences in bloodstream infections and thrombovascular complications between patients using long-term CVCs and those using temporary intravenous catheters. RESULTS: Approximately two thirds of the cohort had a long-term CVC, although rates varied across regions (57% to 75%), health plans (65% to 70%), and insurance coverage (63% to 68%). After propensity score matching, the adjusted hazard ratio for infection was 2.70 (95% CI, 2.31 to 3.16) and thrombovascular complications, 2.61 (95% CI, 2.33 to 2.93) in patients with long-term CVCs compared with those with temporary intravenous catheters. CONCLUSION: Although long-term CVCs may have benefits, they are associated with increased morbidity. Regional and health plan variation in long-term CVC insertion suggests that some of their use reflects provider- or institution-driven variation in practice. Evidence-based guidelines and tools may help decrease discretionary use of long term CVCs. PMID- 26265172 TI - Variation in the Cost of Radiation Therapy Among Medicare Patients With Cancer. AB - PURPOSE: Radiation therapy represents a major source of health care expenditure for patients with cancer. Understanding the sources of variability in the cost of radiation therapy is critical to evaluating the efficiency of the current reimbursement system and could shape future policy reform. This study defines the magnitude and sources of variation in the cost of radiation therapy for a large cohort of Medicare beneficiaries. PATIENTS AND METHODS: We identified 55,288 patients within the SEER database diagnosed with breast, lung, or prostate cancer between 2004 and 2009. The cost of radiation therapy was estimated from Medicare reimbursements. Multivariable linear regression models were used to assess the influence of patient, tumor, and radiation therapy provider characteristics on variation in cost of radiation therapy. RESULTS: For breast, lung, and prostate cancers, the median cost (interquartile range) of a course of radiation therapy was $8,600 ($7,300 to $10,300), $9,000 ($7,500 to $11,100), and $18,000 ($11,300 to $25,500), respectively. For all three cancer subtypes, patient- or tumor related factors accounted for < 3% of the variation in cost. Factors unrelated to the patient, including practice type, geography, and individual radiation therapy provider, accounted for a substantial proportion of the variation in cost, ranging from 44% with breast, 43% with lung, and 61% with prostate cancer. CONCLUSION: In this study, factors unrelated to the individual patient accounted for the majority of variation in the cost of radiation therapy, suggesting potential inefficiency in health care expenditure. Future research should determine whether this variability translates into improved patient outcomes for further evaluation of current reimbursement practices. PMID- 26265173 TI - Impact of the National Cancer Institute Community Cancer Centers Program on Clinical Trial and Related Activities at a Community Cancer Center in Rural Nebraska. AB - PURPOSE: Although 85% of patients with cancer are diagnosed and treated in the community setting, only 3% are enrolled onto clinical trials. Lack of adequate time, infrastructure, resources, incentives, and reimbursement adversely affect clinical trial participation. In July 2007, Saint Francis Cancer Treatment Center (SFCTC) in Grand Island, Nebraska, was selected as one of the initial 16 sites for the National Cancer Institute Community Cancer Centers Program (NCCCP). METHODS: Clinical trial and related activities data at SFCTC 5 years before and 5 years during the NCCCP were gathered and compared. Data included information on patients in clinical trials, number and type of trials, ratio of underserved patients, staffing, collection and storage of tissue samples, availability of new cancer services, and organizational infrastructure and linkage to National Cancer Institute-designated cancer centers. RESULTS: The number and percentage of patients enrolled onto clinical trials increased from 89 (3.2%) to 640 (23%; P<.001). All enrollees were rural Nebraskans, with 70%age > 65 years. Available treatment and nontreatment (eg, prevention, biospecimen,cancer control) trials increased from eight and three per year to 28 and 12 per year (P=.012), respectively. Staffing increased from 1.2 to 3.9 full-time equivalents (P=.012). A genetic counselor, smoking cessation counselor, and outreach project coordinator and two nurse navigators were hired. The number of tissue samples collected and/or stored increased from 26 (19%) to 320 (52%; P<.001). CONCLUSION: NCCCP participation had a direct and positive impact on all activities, with enhanced access to expanded types of trials and cancer care services. Our data demonstrate the feasibility of successful implementation of an expanded spectrum of clinical trials and programs in a rural community. PMID- 26265174 TI - Are Patients With Cancer Less Willing to Share Their Health Information? Privacy, Sensitivity, and Social Purpose. AB - PURPOSE: Growing use of electronic health information increases opportunities to build population cancer databases for research and care delivery. Understanding patient views on reuse of health information is essential to shape privacy policies and build trust in these initiatives. METHODS: We randomly assigned nationally representative participants (N = 3,336) with and without prior cancer to six of 18 scenarios describing different uses of electronic health information. The scenarios varied the user, use, and sensitivity of the information. Participants rated each scenario on a scale of 1 to 10 assessing their willingness to share their electronic health information. We used conjoint analysis to measure the relative importance of each attribute (ie, use, user, and sensitivity). RESULTS: Participants with and without a prior diagnosis of cancer had a similar willingness to share health information (0.27; P = .42). Both cancer and noncancer participants rated the purpose of information use as the most important factor (importance weights, 67.1% and 45.6%, respectively). For cancer participants, the sensitivity of the information was more important (importance weights, 29.8% v 1.2%). However, cancer participants were more willing to share their health information when the information included more sensitive genetic information (0.48; P = .015). Cancer and noncancer respondents rated uses and users similarly. CONCLUSION: The information sharing preferences of participants with and without a prior diagnosis of cancer were driven mainly by the purpose of information reuse. Although conventional thinking suggests patients with cancer might be less willing to share their health information, we found participants with cancer were more willing to share their inherited genetic information. PMID- 26265175 TI - Survey of the State of Implementation of the American Society of Clinical Oncology/Oncology Nursing Society Safety Standards for Chemotherapy Administration in India. AB - PURPOSE: The American Society of Clinical Oncology and the Oncology Nursing Society have proposed a set of standards for safe chemotherapy administration. The state of implementation of these standards in oncologic practices in India is not understood properly. METHODS: An anonymized survey was designed that consisted of items from all 37 standards that were described in the 2013 update of the standards. The survey was distributed via e-mail as well as in paper format among oncologists working in various oncology practices in the country. A standard was considered as fully implemented if more than 90% of the items beneath it had the most positive response (Yes/Always). RESULTS: Responses were obtained from 75 of 114 (65.8%) of the institutions surveyed. Only one institution had fully implemented the standards, whereas only six (8.0%) institutions had implemented more than 90% of the standards fully. The general chemotherapy administration-related domain was implemented fully by the least number of institutions. Although characteristics such as location, funding, and type of institution (teaching or not) failed to influence implementation rates, institutions of respondents who were aware of chemotherapy practice-related standards reported full implementation of a larger number of standards. Lack of national-level guidelines/policies was identified as the most common difficulty in implementing standards. CONCLUSION: This survey indicates that there is an urgent need to formulate national-level guidelines for safe chemotherapy administration. PMID- 26265177 TI - Subcellular trafficking and functional importance of herpes simplex virus type 1 glycoprotein M domains. AB - Herpes simplex virus type 1 (HSV-1) glycoprotein M (gM/UL10) is a 473 aa type III transmembrane protein that resides in various membrane compartments. HSV-1 gM contains several putative trafficking motifs, but their functional relevance remains to be elucidated. We show here that transiently expressed gM 19-343 was sufficient for transport to the trans-Golgi network (TGN), whilst gM 133-473, where the first two transmembrane domains were deleted, and gM 1-342, which lacked the final residue of the last transmembrane domain, were retained in the endoplasmic reticulum (ER), indicating that all transmembrane domains are required for proper folding and ER exit. A series of bacterial artificial chromosome mutants revealed that in addition to the authentic start codon, translation of gM can be initiated at methionine 19 and 133/135. Whilst a protein lacking the first 18 residues supported WT-like growth, gM 133/135-473 resulted in reduced plaque diameters resembling a UL10 deletion mutant. An HSV-1 mutant encoding gM 1-342 showed similar growth characteristics and accumulated non enveloped cytoplasmic particles, whilst gM 1-343 resulted in a gain of function, indicating that all transmembrane domains of the protein are important for viral growth. A C-terminal extension further supported viral propagation; however, the C-terminal trafficking motifs (residues 423-473) were completely dispensable. We propose a functional core within gM 19-343 comprised of all transmembrane domains that is sufficient to target the protein to the TGN, a favoured site for envelopment, and to support viral functions. PMID- 26265176 TI - LC3B globular structures correlate with survival in esophageal adenocarcinoma. AB - BACKGROUND: Esophageal adenocarcinoma has the fastest growing incidence of any solid tumor in the Western world. Prognosis remains poor with overall five-year survival rates under 25 %. Only a limited number of patients benefit from chemotherapy and there are no biomarkers that can predict outcome. Previous studies have indicated that induction of autophagy can influence various aspects of tumor cell biology, including chemosensitivity. The objective of this study was to assess whether expression of the autophagy marker (LC3B) correlated with patient outcome. METHODS: Esophageal adenocarcinoma tumor tissue from two independent sites, was examined retrospectively. Tumors from 104 neoadjuvant naive patients and 48 patients post neoadjuvant therapy were assembled into tissue microarrays prior to immunohistochemical analysis. Kaplan-Meier survival curves and log-rank tests were used to assess impact of LC3B expression on survival. Cox regression was used to examine association with clinical risk factors. RESULTS: A distinct globular pattern of LC3B expression was found to be predictive of outcome in both patient groups, irrespective of treatment (p < 0.001). Multivariate analysis found that this was a strong independent predictor of poor prognosis (p < 0.001). CONCLUSIONS: This distinctive staining pattern of LC3B represents a novel prognostic marker for resectable esophageal adenocarcinoma. PMID- 26265178 TI - Primitive follicular induction in molluscum contagiosum. AB - BACKGROUND: Molluscum contagiosum (MC) is the commonest human poxvirus infection. Follicular induction has rarely been observed in the epidermis surrounding lesions of MC. A virus-induced localized proliferation of germinative/stem cells of the folliculosebaceous-apocrine unit has been suggested as the underlying cause, however few reports of this peculiar phenomenon exist in the literature and the mechanisms involved in this proliferation require further study. METHODS: We prospectively collected MC cases showing multifocal areas of primitive follicular induction involving the adjacent undersurface epidermis. Immunohistochemical expression of BerEP4, PHLDA1 and cytokeratin 20 (CK20) was evaluated in the basaloid germs surrounding the lesions. For PHLDA1, we used epidermal melanocytes as a positive internal control. For BerEP4, we employed a basal cell carcinoma (BCC) and for CK20, colon as positive external controls. An incubation without the primary antibody functioned as an external negative control. RESULTS: All the cases studied showed an intense positive staining of the basaloid buds with BerEP4 and weaker stain for PHLDA1. CK20 showed the presence of scattered Merkel cells within the induced epidermal basaloid proliferations favoring their reactive origin. DISCUSSION: The pathogenetic mechanisms behind the development of these microscopic features and the link between follicular induction and poxvirus infection are explored. Awareness of this unusual phenomenon by dermatopathologists will be helpful in avoiding a misdiagnosis of a superficial BCC in such cases. CONCLUSIONS: BerEP4 and PHLDA1 were consistently expressed in the areas of primitive follicular induction surrounding lesions of MC. CK 20 stained the Merkel cells present in the basaloid buds. All these findings support the reactive origin of this phenomenon, which we believe is most probably viral-induced. PMID- 26265179 TI - Vascularized composite allotransplantation: current standards and novel approaches to prevent acute rejection and chronic allograft deterioration. AB - The advent of more potent immunosuppressants led to the first successful human upper extremity transplantation in 1998. At this time, >100 upper extremity transplants, 30 face transplants, and a variety of other vascularized composite allotransplantation (VCA) procedures have been performed around the world. VCA recipients present unique challenges for transplantation. The incidence of acute rejection exceeds 80% in hand and face transplantation and is well documented, whereas reports about antibody-mediated rejection and chronic rejection remain scarce. Immunosuppression protocols commonly used at US centers are derived from solid organ transplantation protocols. Novel approaches to minimize rejections in VCA may include improved HLA matching and considerations toward cytomegalovirus infection status. New graft preservation techniques may decrease immunogenicity prior to transplant. Novel monitoring methods such as valid biomarkers, ultrasound biomicroscopy, and sentinel flaps may enable earlier diagnosis of rejection. Cell-based therapies are being explored to achieve immunosuppressive regimen minimization or even tolerance induction. The efficacy of local immunosuppression in clinical VCA remains controversial. In conclusion, although immunosuppressive strategies adapted from SOT have demonstrated good midterm results, focusing on the unique features of VCA grafts may enable additional, more specific treatment strategies in the future and improved long-term graft outcomes. PMID- 26265180 TI - Identification and functional analysis of olfactory receptor family reveal unusual characteristics of the olfactory system in the migratory locust. AB - Locusts represent the excellent model of insect olfaction because the animals are equipped with an unusual olfactory system and display remarkable density dependent olfactory plasticity. However, information regarding receptor molecules involved in the olfactory perception of locusts is very limited. On the basis of genome sequence and antennal transcriptome of the migratory locust, we conduct the identification and functional analysis of two olfactory receptor families: odorant receptors (ORs) and ionotropic receptors (IRs). In the migratory locust, there is an expansion of OR family (142 ORs) while distinctly lower number of IR genes (32 IRs) compared to the repertoires of other insects. The number of the locust OR genes is much less than that of glomeruli in antennal lobe, challenging the general principle of the "one glomerulus-one receptor" observed in other insects. Most OR genes are found in tandem arrays, forming two large lineage specific subfamilies in the phylogenetic tree. The "divergent IR" subfamily displays a significant contraction, and most of the IRs belong to the "antennal IR" subfamily in the locust. Most ORs/IRs have olfactory-specific expression while some broadly- or internal-expressed members are also found. Differing from holometabolous insects, the migratory locust contains very similar expression profiles of ORs/IRs between nymph and adult stages. RNA interference and behavioral assays indicate that an OR-based signaling pathway, not IR-based, mediates the attraction of locusts to aggregation pheromones. These discoveries provide insights into the unusual olfactory system of locusts and enhance our understanding of the evolution of insect olfaction. PMID- 26265182 TI - Femtosecond UV-laser pulses to unveil protein-protein interactions in living cells. AB - A hallmark to decipher bioprocesses is to characterize protein-protein interactions in living cells. To do this, the development of innovative methodologies, which do not alter proteins and their natural environment, is particularly needed. Here, we report a method (LUCK, Laser UV Cross-linKing) to in vivo cross-link proteins by UV-laser irradiation of living cells. Upon irradiation of HeLa cells under controlled conditions, cross-linked products of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were detected, whose yield was found to be a linear function of the total irradiation energy. We demonstrated that stable dimers of GAPDH were formed through intersubunit cross-linking, as also observed when the pure protein was irradiated by UV-laser in vitro. We proposed a defined patch of aromatic residues located at the enzyme subunit interface as the cross-linking sites involved in dimer formation. Hence, by this technique, UV-laser is able to photofix protein surfaces that come in direct contact. Due to the ultra-short time scale of UV-laser-induced cross-linking, this technique could be extended to weld even transient protein interactions in their native context. PMID- 26265183 TI - Defining and treating high-risk multiple myeloma. AB - Multiple myeloma (MM) is more recently being recognized as a heterogeneous group of disease with variability in outcomes based on specific clinical and biologic predictors. MM patients can be broadly categorized into standard, intermediate and high risk for disease relapse, morbidity and mortality. The high-risk features include patient-specific factors such as old age, poor performance status and comorbidities; clinical features such as primary plasma cell leukemia and extramedullary disease; disease-specific biologic features such as deletion 17p, t(4;14) and high-risk gene expression profiling signatures. The current paper reviews the available data on best therapeutic approaches for high-risk MM. PMID- 26265181 TI - The multifaceted role of PIP2 in leukocyte biology. AB - Phosphatidylinositol 4,5-bisphosphate (PIP2) represents about 1 % of plasma membrane phospholipids and behaves as a pleiotropic regulator of a striking number of fundamental cellular processes. In recent years, an increasing body of literature has highlighted an essential role of PIP2 in multiple aspects of leukocyte biology. In this emerging picture, PIP2 is envisaged as a signalling intermediate itself and as a membrane-bound regulator and a scaffold of proteins with specific PIP2 binding domains. Indeed PIP2 plays a key role in several functions. These include directional migration in neutrophils, integrin-dependent adhesion in T lymphocytes, phagocytosis in macrophages, lysosomes secretion and trafficking at immune synapse in cytolytic effectors and secretory cells, calcium signals and gene transcription in B lymphocytes, natural killer cells and mast cells. The coordination of these different aspects relies on the spatio-temporal organisation of distinct PIP2 pools, generated by the main PIP2 generating enzyme, phosphatidylinositol 4-phosphate 5-kinase (PIP5K). Three different isoforms of PIP5K, named alpha, beta and gamma, and different splice variants have been described in leukocyte populations. The isoform-specific coupling of specific isoforms of PIP5K to different families of activating receptors, including integrins, Fc receptors, toll-like receptors and chemokine receptors, is starting to be reported. Furthermore, PIP2 is turned over by multiple metabolising enzymes including phospholipase C (PLC) gamma and phosphatidylinositol 3-kinase (PI3K) which, along with Rho family small G proteins, is widely involved in strategic functions within the immune system. The interplay between PIP2, lipid-modifying enzymes and small G protein-regulated signals is also discussed. PMID- 26265184 TI - Monoclonal antibodies in the treatment of multiple myeloma: current status and future perspectives. AB - The treatment landscape for patients with multiple myeloma (MM) is constantly evolving. Over the past decade, the introduction of novel agents such as proteasome inhibitors and immunomodulatory drugs has led to notable changes in therapeutic strategy, and improvements in survival, yet MM remains incurable in the vast majority of cases. More recently, a targeted approach to MM treatment has emerged, using monoclonal antibodies (mAbs) to target antigens expressed on the surface of MM cells. MAbs tested to date kill MM cells via the host's immune system and/or by promoting apoptosis, and appear to have generally improved tolerability compared with currently available treatments. Due to their distinct mode of action, mAbs are promising both for patients who have exhausted current regimens, and as part of first-line treatments in newly diagnosed patients. This review examines the recent developments in mAb-based therapy for MM, primarily focused on those agents in ongoing clinical testing. PMID- 26265186 TI - Metal-Organic Frameworks (MOFs) of a Cubic Metal Cluster with Multicentered Mn(I) Mn(I) Bonds. AB - MOFs with both multicentered metal-metal bonds and low-oxidation-state (LOS) metal ions have been underexplored hitherto. Here we report the first cubic [Mn(I) 8 ] cluster-based MOF (1) with multicentered Mn(I)-Mn(I) bonds and +1 oxidation state of manganese (Mn(I) or Mn(I)), as is supported by single-crystal structure determination, XPS analyses, and quantum chemical studies. Compound 1 possesses the shortest Mn(I)-Mn(I) bond of 2.372 A. Theoretical studies with density functional theory (DFT) reveal extensive electron delocalization over the [Mn(I) 8 ] cube. The 48 electrons in the [Mn(I) 8 ] cube fully occupy half of the 3d-based and the lowest 4s-based bonding orbitals, with six electrons lying at the nonbonding 3d-orbitals. This bonding feature renders so-called cubic aromaticity. Magnetic properties measurements show that 1 is an antiferromagnet. This work is expected to inspire further investigation of cubic metal-metal bonding, MOF materials with LOS metals, and metalloaromatic theory. PMID- 26265185 TI - HSP90 inhibition leads to degradation of the TYK2 kinase and apoptotic cell death in T-cell acute lymphoblastic leukemia. AB - We previously found that tyrosine kinase 2 (TYK2) signaling through its downstream effector phospho-STAT1 acts to upregulate BCL2, which in turn mediates aberrant survival of T-cell acute lymphoblastic leukemia (T-ALL) cells. Here we show that pharmacologic inhibition of heat shock protein 90 (HSP90) with a small molecule inhibitor, NVP-AUY922 (AUY922), leads to rapid degradation of TYK2 and apoptosis in T-ALL cells. STAT1 protein levels were not affected by AUY922 treatment, but phospho-STAT1 (Tyr-701) levels rapidly became undetectable, consistent with a block in signaling downstream of TYK2. BCL2 expression was downregulated after AUY922 treatment, and although this effect was necessary for AUY922-induced apoptosis, it was not sufficient because many T-ALL cell lines were resistant to ABT-199, a specific inhibitor of BCL2. Unlike ABT-199, AUY922 also upregulated the proapoptotic proteins BIM and BAD, whose increased expression was required for AUY922-induced apoptosis. Thus, the potent cytotoxicity of AUY922 involves the synergistic combination of BCL2 downregulation coupled with upregulation of the proapoptotic proteins BIM and BAD. This two-pronged assault on the mitochondrial apoptotic machinery identifies HSP90 inhibitors as promising drugs for targeting the TYK2-mediated prosurvival signaling axis in T-ALL cells. PMID- 26265187 TI - Plain radiography in children with spoke wheel injury: A retrospective cohort study. AB - BACKGROUND AND PURPOSE: Bicycle spoke injury (BSI) mostly occurs in children as a result of entrapment of the leg in the bicycle spokes. No guideline or protocol exists that defines what type of radiography is indicated to diagnose or rule out a fracture commonly associated with these injuries. The aim of this study was (1) to evaluate the type of radiographs that are obtained in children with BSI, (2) to assess in which anatomical regions fractures occur and (3) to evaluate on which radiographs a fracture can be detected in children with BSI. PATIENTS AND METHODS: A retrospective cohort study was performed in paediatric patients presenting at the Emergency Department (ED) of a university hospital with a paediatric surgery department between June 2008 and December 2013. RESULTS: In 99 of the 320 children (31.4%) evaluated with radiography following BSI a fracture was diagnosed. In almost two third of the patients (63%) radiographic imaging of two or more anatomical regions was performed. In 98 children (99%) the fracture was located at the distal tibia or fibula. All fractures were diagnosed on a radiograph of the ankle or lower leg (including the ankle region). No fractures of the foot were diagnosed. CONCLUSION: We suggest that in children with a clinical suspicion of a fracture at the ankle region, in which no fracture is seen at the radiograph of the ankle, no additional radiographs are necessary. PMID- 26265188 TI - Coatings of Eudragit(r) RL and L-55 Blends: Investigations on the Drug Release Mechanism. AB - In a previous study, generally lower drug release rates from RL:L55 blend coated pellets in neutral/basic release media than in acidic release media were reported. The aim of this study was to obtain information on the drug release mechanism of solid dosage forms coated with blends of Eudragit(r) RL (RL) and Eudragit(r) L-55 (L55). Swelling experiments with free films were analyzed spectroscopically and gravimetrically to identify the physicochemical cause for this release behavior. With Raman spectroscopy, the swelling of copolymer films could be monitored. IR spectroscopic investigations on RL:L55 blends immersed in media at pH 6.8 confirmed the formation of interpolyelectrolyte complexes (IPECs) that were not detectable after swelling in hydrochloric acid pH 1.2. Further investigations revealed that these IPECs decreased the extent of ion exchange between the quaternary ammonium groups of RL and the swelling media. This is presumably the reason for the previously reported decreased drug permeability of RL:L55 coatings in neutral/basic media as ion exchange is the determining factor in drug release from RL coated dosage forms. Gravimetric erosion studies confirmed that L55 was not leached out of the film blends during swelling in phosphate buffer pH 6.8. In contrast to all other investigated films, the 4:1 (RL:L55) blend showed an extensive swelling within 24 h at pH 6.8 which explains the reported sigmoidal release behavior of 4:1 blend coated pellets. These results help to understand the release behavior of RL:L55 blend coated solid dosage forms. PMID- 26265189 TI - Process and Method Variability Modeling to Achieve QbD Targets. AB - A statistical modeling tool is presented that enables real-time viewing of how changes in method, process, and stability variability/bias impact product acceptance rate. The tool can be used to set and justify specifications. As needed, additional sources of variability/bias can be added to further optimize the tool's prediction power. The tool can be used to assess each manufacturing run to ensure the process is in control. Aberrant results can then be investigated to see what source of variability/bias may have changed. To enable continuous improvement, the impact of new processes, methods, or technologies can also be addressed and such changes justified. PMID- 26265190 TI - Effervescence Assisted Fusion Technique to Enhance the Solubility of Drugs. AB - The solubility of five poorly soluble drugs was enhanced by using an effervescence assisted solid dispersion (EASD) technique. EASDs were prepared by using modified fusion method. Drug and hydrophilic carrier were melted, and in this molten mixture, effervescence was generated by adding effervescence couple comprising organic acid (citric acid) and carbonic base (sodium bicarbonate). Solubility of drug powders, solid dispersions, and EASDs was determined at 25 degrees C using shake flask method. Atorvastatin calcium, cefuroxime axetil, clotrimazole, ketoconazole, and metronidazole benzoate were estimated using a spectrophotometer at 246, 280, 260, 230, and 232 nm (lambda max), respectively. Solubility of atorvastatin calcium (from 100 to 345 MUg/ml), cefuroxime axetil (from 441 to 1948 MUg/ml), clotrimazole (from 63 to 677 MUg/ml), ketoconazole (from 16 to 500 MUg/ml), and metronidazole benzoate (from 112 to 208 MUg/ml) in EASDs was enhanced by 3.45-, 4.4-, 10.7-, 31.2-, and 1.8-fold, respectively. Scanning electron micrographs of drug powder, solid dispersion, and EASDs were compared. Scanning electron micrographs of EASDs showed a uniform distribution of drug particles in the carrier matrix. Morphology (size and shape) of cefuroxime axetil particles was altered in solid dispersion as well as in EASD. EASDs showed better solubility enhancement than conventional solid dispersions. The present technique is better suitable for drugs having a low melting point or melt without charring. Effervescence assisted fusion technique of preparing solid dispersions can be employed for enhancing solubility, dissolution, and bioavailability of poorly soluble drugs. PMID- 26265191 TI - Effect of therapeutic ultrasound on brain angiogenesis following intracerebral hemorrhage in rats. AB - Intracerebral hemorrhage (ICH) can produce severe neurological deficits in stroke survivors. However, few effective approaches are available to improve the recovery from ICH. Given that therapeutic ultrasound exposure can enhance on angiogenesis in peripheral tissues, the present study was designed to examine the effects of therapeutic ultrasound exposure on the brain angiogenesis following ICH. To this end, we applied once daily therapeutic ultrasound treatment to rats for 7 consecutive days after intracranial infusion of vehicle (Sham control) or collagenase (ICH). Repeated exposure to the low intensity of therapeutic ultrasound decreased behavioral scores in ICH rats, but not in sham control rats. Such an effect was correlated with an increased number of vessel-like structures and microvessels and PCNA positive cells in vWF-positive blood vessels in perihematomal brain tissues at post-ICH day 7. Furthermore, immunohistochemistry and western blotting results showed that ICH trigged the expression of extracellular matrix (ECM)-related molecules, including collagen Is, III, and IV, as well as integrins alphavbeta3 and alpha5beta1, and exposure to therapeutic ultrasound increased the expression of these molecules. Therefore, our results indicated that repeated exposure to a low intensity of therapeutic ultrasound can increase the expression of collagen and integrins of ECM-related molecules, promote the formation of a large number of vessel-like structure and capillaries around the hematoma, and accelerate the recovery of neurological function impaired by ICH. PMID- 26265192 TI - Near infrared spectroscopy (NIRS) to assess the effects of local ischemic preconditioning in the muscle of healthy volunteers and critically ill patients. AB - Near-infrared spectroscopy (NIRS) permits non-invasive evaluation of tissue oxygen saturation (StO2). A vascular occlusion test (VOT) produces transient controlled ischemia similar to that used in ischemic preconditioning. We hypothesized that we could evaluate local responses to ischemic preconditioning by performing repeated VOTs and observing the changes in different NIRS VOT derived variables. In healthy volunteers (n=20), four VOTs were performed at 30 min intervals on one day and, in a second group (n=21), two VOTs with time intervals of 5, 15 or 30min were performed on 3 separate days. Two cohorts of patients, one with circulatory shock (n=23) and a hemodynamically stable group (n=20), were also studied, repeating the VOT twice with a 5-min interval. In the 1-day volunteers, there was a median decrease of 15 (6-21)% in the Desc slope (StO2 decrease during VOT) after the second VOT, but no significant change in the Asc slope (StO2 increase after VOT). In the 3-day volunteers, the Desc slope also decreased, regardless of the time interval between VOTs. There was no overall decrease in the Desc slope in either patient cohort with repeated VOTs but there was marked individual patient variability. Patients in whom the Desc slope decreased had less organ dysfunction at admission, required less norepinephrine (0.00 vs 0.08mcg/kg/min, p=0.02), less frequently had sepsis (12 vs 50%, p=0.02) and had a lower mortality (6 vs 39%, p=0.03) compared to those in whom it did not decrease. Repeated NIRS VOT can non-invasively assess the local effects of ischemic preconditioning in the muscle. PMID- 26265193 TI - Surgical manifestations of gastrointestinal cytomegalovirus infection in children: Clinical audit and literature review. AB - INTRODUCTION: Gastrointestinal sequelae of cytomegalovirus are rare, usually associated with significant immune compromise, and carry a high morbidity and mortality. Gastrointestinal disease frequently requires surgical intervention for diagnosis and management. AIM: The aim of the study is to evaluate the incidence, presentation and management of gastrointestinal cytomegalovirus disease in a pediatric population. METHOD: Between January 2003 and June 2011, a retrospective folder review was conducted of all symptomatic children with proven CMV disease, presenting to the surgical service. Eligible patients were identified using the surgical, histopathology and serology databases. RESULTS: Thirty-eight patients (1.8/1000 surgical admissions) were identified with a median presenting age of 5months (range 3days-12years). Esophagitis (n=18) and small bowel disease (n=16) predominated, but CMV was seen throughout the gastrointestinal tract. Risk factors included HIV infection (n=21, 55%) and recent gastrointestinal surgery or infection (n=10, 26%). Characteristic multiple jejunoileal perforations were seen in six patients. Compared to upper GIT disease, intestinal involvement was associated with younger age and doubled mortality. In HIV-infected children, median CD4 (%) was lower in intestinal compared to upper gastrointestinal disease. Morbidities included anastomotic breakdowns (5), anastomotic strictures (3), relook laparotomies (10), resistant esophageal strictures (5) and prolonged parenteral nutrition (5). Anti-CMV drugs were given in 63%. Overall mortality was 32% (12/38) and was associated with lower GIT disease. CONCLUSION: Invasive CMV gastrointestinal disease in our children was predominantly HIV-associated, or followed a major lower gastrointestinal inflammatory insult in infants younger than 6months. Successful therapy requires a high index of suspicion of active CMV disease to allow early implementation of CMV viral load control and aggressive treatment of the underlying immune impairment. Multiple surgical interventions are often required for both tissue diagnosis and management of acute and chronic complications. CMV-viral-load-tailored anti-CMV therapy is supported by recent literature. PMID- 26265195 TI - Interaction of Policy, Politics, and Health. PMID- 26265194 TI - Distinct patterns of peritumoral histological findings in subtypes of intraductal papillary mucinous neoplasms of the pancreas. AB - Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are primary pancreatic neoplasms that can act as precursors to invasive adenocarcinoma of the pancreas. The peritumoral stroma has been increasingly recognized to play an important role in many types of tumors. Therefore, to investigate the clinicopathological significance of the peritumoral stroma in IPMNs, we examined the histological features of the peritumoral stroma in each subtype and histological grade of IPMNs. Eighty-two patients with IPMN, who underwent surgical resection, were reviewed clinicopathologically. Intraductal papillary mucinous neoplasms (86 lesions in total) were histologically subclassified into gastric (n = 51), intestinal (n = 22), pancreatobiliary (n = 11), and oncocytic (n = 2) subtypes. Peritumoral histological features between the gastric and intestinal subtypes were evaluated by each histological grade. The results showed that subepithelial edema and inflammatory cell infiltration were more commonly observed in the gastric subtype (74% and 79%, respectively) than in the intestinal subtype (12% and 25%, respectively) of low-grade IPMNs. On the other hand, mucus lakes were more commonly observed in the intestinal subtype (100%) than in the gastric subtype (0%) of high-grade IPMNs. In addition, pancreatobiliary subtype IPMNs tended to exhibit acute inflammation such as neutrophil predominance. This study showed that peritumoral histological features differed among subtypes of IPMNs from low-grade tumors. These differences suggest the possibility that each subtype of IPMNs has a distinct mechanism from an early stage of tumor progression, which is reflected in the properties of the peritumoral stroma. PMID- 26265196 TI - Sequential Healing at Implants with Different Configuration and Modified Surfaces: An Experimental Study in the Dog. AB - PURPOSE: To evaluate the peri-implant soft and hard tissue adaptation at implants with different modified surfaces and configurations. MATERIALS AND METHODS: Six Beagle dogs were used. Mandibular premolars and first molars were extracted bilaterally. After 3 months, full-thickness flaps were elevated, and two different types of trans-mucosal implants (ICX-Gold(r), Medentis Medical GmbH, Dernau, Germany and SLActive(r), Institute Straumann, Bern, Switzerland) and two different surfaces were randomly installed in the distal regions of one side of the mandible. Abutments were applied, and a nonsubmerged healing was allowed. After 1 month, the procedures were performed in the other side of the mandible, and after a further month, the animals were sacrificed, biopsies were collected, and ground sections prepared for histological examination. RESULTS: Similar results in marginal bone and soft tissues dimensions were observed after 1 month of healing at the two implant systems used, and no major changes could be observed after 2 months of healing. After 1 month, the percentage of new bone was 69.0% and 68.8% at ICX-Gold and SLActive surfaces, respectively. After 2 months, the percentage of new bone was 67.8% and 71.9% at ICX-Gold Medentis and SLActive surfaces, respectively. No statistically significant differences in osseointegration were found. CONCLUSION: The two implant systems used resulted in similar osseointegration after 1 and 2 months of healing. PMID- 26265197 TI - Topical diclofenac does not affect the antiplatelet properties of aspirin as compared to the intermediate effects of oral diclofenac: A prospective, randomized, complete crossover study. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) adversely interact with aspirin, diminishing its antiplatelet effect and potentially placing patients at an increased risk for recurrent thrombotic events. This crossover study aimed to determine whether the topical NSAID diclofenac epolamine 1.3% patch or oral diclofenac 50 mg interfered with the antiplatelet effects of aspirin 325 mg. Twelve healthy men and women aged 18-50 were included. Participants were randomized into 5 treatment arms: aspirin, diclofenac potassium 50 mg, diclofenac patch, diclofenac potassium plus ASA 325 mg, and diclofenac patch plus aspirin. Platelet responsiveness was determined using whole-blood impedance aggregation (WBA) to collagen 1 MUg/mL and arachidonic acid (AA) 0.5 mM and was sampled every 2 hours. No significant difference in platelet function was observed following the diclofenac patch and aspirin vs aspirin alone. Oral diclofenac produced a mixed effect with significant reduction in platelet inhibition at hour 2 and hour 8 following aspirin administration. Topical diclofenac does not significantly interfere with the antiplatelet effects of aspirin and may be a safer alternative to the oral formulation. PMID- 26265198 TI - Spata19 is critical for sperm mitochondrial function and male fertility. AB - Haploid round spermatids undergo differentiation and morphogenesis during spermiogenesis, resulting in mature spermatozoa. The molecular details underlying this transformation, however, remain poorly understood. In this study, we generated and analyzed germ cell-specific Spata19 knockout mice (Spata19(flox/flox) ; Stra8-Cre; hereafter termed "Spata19 cKO") to assess the model that SPATA19 contributes to mitochondrial function in differentiating spermatids. Spata19-cKO males were infertile, as their sperm exhibited disorganized mitochondrial structure; furthermore, their sperm-abundance of mitochondrial proteins, activities of mitochondrial respiratory chain complex IV, and ATP levels were significantly reduced. Yet, the infertility of Spata19-cKO males was rescued by intracytoplasmic sperm injection, so the sperm are capable of initiating development. Collectively, our findings suggest that SPATA19 plays an important role in sperm motility by regulating the organization and function of the mitochondria. PMID- 26265199 TI - Synthesis, Biological Evaluation and QSAR Studies of Newer Isoxazole Derivatives. AB - A series of newer 3-(4'-methoxyphenyl)-5-substituted phenylisoxazoles derivatives have been synthesized by reacting hydroxylamine hydrochloride with chalcones. The chalcones were formed by reacting different aromatic aldehydes with 4 methoxyacetophenone in presence of aqueos potassium hydroxide (KOH). The purity of all the synthesized compounds was checked by recording their melting points and the retention Factors (Rf) values from thin layer chromatography. The structures of the compounds were characterized by recording their infrared (IR) spectra and confirmed by recording their nuclear magnetic resonance ((1)H NMR) spectra. The acute toxicity study was carried out on all the synthesized compounds and they were screened for their antiinflammatory activity by carrageenan induced rat paw edema method. Anti-inflammatory studies showed statistically significant activity when compared to the control, indomethacin. The two most potent compounds giving good anti-inflammatory activity were further evaluated for their antiulcer activity. The compounds were subjected to quantitative structure activity relationships (QSAR) studies. A close correlation between the observed and the predicted anti-inflammatory activity (Log % inhibition) for the compounds indicated the development of the best QSAR model. The synthesized compounds were found to be non-ulcerogenic as compared to the standard, aspirin. PMID- 26265200 TI - Probing the Role of Side-Chain Interconnecting Groups in the Structural Hydrophobicity of Comblike Fluorinated Polystyrene by Solid-State NMR Spectroscopy. AB - In order to probe the role of side-chain interconnecting groups (-O-, -S-, and SO2- linkages between the polystyrene (PST) main chain and fluorooctyl side chain) in the hydrophobicity of the comblike fluorinated polystyrenes, the molecular motion and structure of polymers are explored using the spin-lattice relaxation times (T1 and T1rho) by solid-state (1)H and (19)F nuclear magnetic resonance spectroscopy. The chain-end motions of the polystyrene main chain and the fluorooctyl side chain are homogeneous, regardless of the interconnecting groups, which means that the chain-end motions of the main chain and the side chain maintain consistency, and these are irrelevant to each other. However, the local dynamic of the main chain shows the structural heterogeneity composed of the mobile and rigid regions, attributed to the rigidity of the side chain. The mobile dynamic portions of the main chain for PST-O and PST-S increase, and their rigid dynamic portions decrease as the temperature increases, whereas the ratio of structural heterogeneity for PST-SO2 is maintained despite increasing temperature. The activation energies (Ea) corresponding to the local motion of fluorooctyl side chains for PST-O and PST-S are drastically increased on the fast motion side compared to the slow motion side, suggesting the motional transformation of side chains for PST-O and PST-S from the small local motion into the large-scale movements related to a cooperative segmental motion when heated. Also, the local motion of the fluorooctyl side chain for PST-SO2 has similar Ea values on both sides, indicating that the relaxation time of PST-SO2 does not change with temperature. Therefore, PST-SO2 is structurally more stable than PST-O or PST-S, which can be attributed to the densely packed fluorooctyl side chain structure caused by the large dipole moment of the sulfone interconnecting group. PMID- 26265201 TI - Impact of Risk Assessment and Tailored versus Nontailored Risk Information on Colorectal Cancer Testing in Primary Care: A Randomized Controlled Trial. AB - BACKGROUND: Colorectal cancer screening is effective but underused. Guidelines for which tests are recommended and at what intervals depend on specific risks. We developed a tablet-based Cancer Risk Intake System (CRIS) that asks questions about risk prior to appointments and generates tailored printouts for patients and physicians summarizing and matching risk factors with guideline-based recommendations. METHODS: Randomized controlled trial among patients who: (i) used CRIS and they and their physicians received tailored printouts; (ii) used CRIS to answer questions but received standard information about cancer screening while their physicians received a standard electronic chart prompt indicating they were age-eligible but not currently adherent for colorectal cancer screening; or (iii) comprised a no-contact group that neither used CRIS nor received any information while their physicians received the standard prompt. Participation in testing was assessed via electronic medical record at 12 months. RESULTS: Participation in any colorectal cancer testing was three times higher for those who used the CRIS and received any printed materials, compared with no contact controls (47% vs. 16%; P < 0.0001). Among CRIS users ages 50 and older, participation in any testing was higher in the tailored group (53% vs. 44%, P = 0.023). CONCLUSION: Use of CRIS and receipt of any information facilitated participation in testing. There was more testing participation in the CRIS tailored than nontailored group. IMPACT: Asking patients questions about their specific risk factors and giving them and their providers information just prior to an appointment may increase participation in colorectal cancer testing. Tailoring the information has some added benefit. PMID- 26265202 TI - Prospectively Identified Incident Testicular Cancer Risk in a Familial Testicular Cancer Cohort. AB - BACKGROUND: Human testicular germ cell tumors (TGCT) have a strong genetic component and a high familial relative risk. However, linkage analyses have not identified a rare, highly penetrant familial TGCT (FTGCT) susceptibility locus. Currently, multiple low-penetrance genes are hypothesized to underlie the familial multiple-case phenotype. The observation that two is the most common number of affected individuals per family presents an impediment to FTGCT gene discovery. Clinically, the prospective TGCT risk in the multiple-case family context is unknown. METHODS: We performed a prospective analysis of TGCT incidence in a cohort of multiple-affected-person families and sporadic-bilateral case families; 1,260 men from 140 families (10,207 person-years of follow-up) met our inclusion criteria. Age-, gender-, and calendar time-specific standardized incidence ratios (SIR) for TGCT relative to the general population were calculated using SEER*Stat. RESULTS: Eight incident TGCTs occurred during prospective FTGCT cohort follow-up (versus 0.67 expected; SIR = 11.9; 95% CI, 5.1 23.4; excess absolute risk = 7.2/10,000). We demonstrate that the incidence rate of TGCT is greater among bloodline male relatives from multiple-case testicular cancer families than that expected in the general population, a pattern characteristic of adult-onset Mendelian cancer susceptibility disorders. Two of these incident TGCTs occurred in relatives of sporadic-bilateral cases (0.15 expected; SIR = 13.4; 95% CI, 1.6-48.6). CONCLUSIONS: Our data are the first to indicate that despite relatively low numbers of affected individuals per family, members of both multiple-affected-person FTGCT families and sporadic-bilateral TGCT families comprise high-risk groups for incident testicular cancer. IMPACT: Men at high TGCT risk might benefit from tailored risk stratification and surveillance strategies. PMID- 26265204 TI - Accessibility and Quality of Online Cancer-Related Clinical Trial Information for Naive Searchers. AB - Although the Internet may help to increase cancer patients' awareness of clinical trials, little is known about the accessibility and quality of online clinical trial information. We simulated the experience of a naive cancer patient without clinical trial knowledge by searching three popular search engines for treatment information for breast, lung, and prostate cancer, and myelodysplastic syndromes (MDS). Two coders independently evaluated website content for accessibility and quality. We screened 120 websites and identified 40 unique sites for analysis. Overall, 85% [95% confidence interval (CI), 70%-94%] of sites mentioned clinical trials on the landing page and 68% (51%-81%) included links to specific trials. Overall readability was poor. Approximately half of websites (36%-68%) included information on the potential benefits and risks of clinical trials and 40% provided information about when the site had been updated (25%-57%). Among sites with links to specific clinical trials, only 44% (25%-65%) provided an interactive interface that would allow patients to customize search results; breast (100%) and prostate (50%) sites were more interactive than lung (25%) and MDS (14%; P = 0.007). Although cancer clinical trial information is widely available on the Internet, its quality is highly variable. Given the fact that many emerging cancer therapeutics are personalized based on disease or genomic characteristics, interactive web-based interfaces could serve as powerful vehicles to help patients locate appropriate clinical trials. Without enhanced efforts to ensure greater interactivity of cancer treatment websites, patient awareness of relevant clinical trials may remain low. PMID- 26265203 TI - Longitudinal Study of DNA Methylation of Inflammatory Genes and Cancer Risk. AB - BACKGROUND: Chronic inflammation plays a key role in cancer etiology. DNA methylation modification, one of the epigenetic mechanisms regulating gene expression, is considered a hallmark of cancer. Human and animal models have identified numerous links between DNA methylation and inflammatory biomarkers. Our objective was to prospectively and longitudinally examine associations between methylation of four inflammatory genes and cancer risk. METHODS: We included 795 Normative Aging Study participants with blood drawn one to four times from 1999 to 2012 (median follow-up, 10.6 years). Promoter DNA methylation of IL6, ICAM-1, IFN, and TLR2 in blood leukocytes was measured using pyrosequencing at multiple CpG sites and averaged by gene for data analysis. We used Cox regression models to examine prospective associations of baseline and time-dependent methylation with cancer risk and compared mean methylation differences over time between cancer cases and cancer-free participants. RESULTS: Baseline IFN hypermethylation was associated with all-cancer (HR, 1.49; P = 0.04) and prostate cancer incidence (HR, 1.69; P = 0.02). Baseline ICAM-1 and IL6 hypermethylation were associated with prostate cancer incidence (HR, 1.43; P = 0.02; HR, 0.70; P = 0.03, respectively). In our time-dependent analyses, IFN hypermethylation was associated with all-cancer (HR, 1.79; P = 0.007) and prostate cancer (HR, 1.57; P = 0.03) incidence; and ICAM-1 and IL6 hypermethylation were associated with prostate cancer incidence (HR, 1.39; P = 0.02; HR, 0.69; P = 0.03, respectively). We detected significant ICAM-1 hypermethylation in cancer cases (P = 0.0003) 10 to 13 years prediagnosis. CONCLUSION: Hypermethylation of IFN and ICAM-1 may play important roles in early carcinogenesis, particularly that of prostate cancer. IMPACT: These methylation changes could inform the development of early detection biomarkers and potential treatments of inflammation-related carcinogenesis. PMID- 26265205 TI - 3D Mesoporous Graphene: CVD Self-Assembly on Porous Oxide Templates and Applications in High-Stable Li-S Batteries. AB - A nanostructured carbon with high specific surface area (SSA), tunable pore structure, superior electrical conductivity, mechanically robust framework, and high chemical stability is an important requirement for electrochemical energy storage. Porous graphene fabricated by chemical activation and liquid etching has a high surface area but very limited volume of electrochemically accessible mesopores. Herein, an effective strategy of in situ formation of hierarchically mesoporous oxide templates with small pores induced by Kirkendall diffusion and large pores attributed to evaporation of deliberately introduced volatile metal is proposed for chemical vapor deposition assembly of porous graphene frameworks (PGFs). The PGFs inherit the hierarchical mesoporous structure of the templates. A high SSA of 1448 m(2) g(-1), 91.6% of which is contributed by mesopores, and a mesopore volume of 2.40 cm(3) g(-1) are attained for PGFs serving as reservoirs of ions or active materials in electrochemical energy storage applications. When the PGFs are applied in lithium-sulfur batteries, a very high sulfur utilization of 71% and a very low fading rate of ~0.04% per cycle after the second cycle are achieved at a current rate of 1.0 C. This work provides a general strategy for the rational construction of mesoporous structures induced by a volatile metal, with a view toward the design of hierarchical nanomaterials for advanced energy storage. PMID- 26265207 TI - Occipital neuralgia after scalp biopsy and curettage. PMID- 26265206 TI - Cell cycle control, DNA damage repair, and apoptosis-related pathways control pre ameloblasts differentiation during tooth development. AB - BACKGROUND: Ameloblast differentiation is the most critical stepwise process in amelogenesis, and it is controlled by precise molecular events. To better understand the mechanism controlling pre-ameloblasts (PABs) differentiation into secretory ameloblasts (SABs), a more precise identification of molecules and signaling networks will elucidate the mechanisms governing enamel formation and lay a foundation for enamel regeneration. RESULTS: We analyzed transcriptional profiles of human PABs and SABs. From a total of 28,869 analyzed transcripts, we identified 923 differentially expressed genes (DEGs) with p < 0.05 and Fold change > 2. Among the DEGs, 647 genes showed elevated expression in PABs compared to SABs. Notably, 38 DEGs displayed greater than eight-fold changes. Comparative analysis revealed that highly expressed genes in PABs were involved in cell cycle control, DNA damage repair and apoptosis, while highly expressed genes in SABs were related to cell adhesion and extracellular matrix. Moreover, coexpression network analysis uncovered two highly conserved sub-networks contributing to differentiation, containing transcription regulators (RUNX2, ETV1 and ETV5), solute carrier family members (SLC15A1 and SLC7A11), enamel matrix protein (MMP20), and a polymodal excitatory ion channel (TRPA1). CONCLUSIONS: By combining comparative analysis and coexpression networks, this study provides novel biomarkers and research targets for ameloblast differentiation and the potential for their application in enamel regeneration. PMID- 26265208 TI - Can Near-infrared Spectroscopy Detect and Differentiate Implant-associated Biofilms? AB - BACKGROUND: Established bacterial diagnostic techniques for orthopaedic-related infections rely on a combination of imperfect tests that often can lead to negative culture results. Spectroscopy is a tool that potentially could aid in rapid detection and differentiation of bacteria in implant-associated infections. QUESTIONS/PURPOSES: We asked: (1) Can principal component analysis explain variation in spectral curves for biofilm obtained from Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa? (2) What is the accuracy of Fourier transformed-near infrared (FT-NIR)/multivariate data analysis in identifying the specific species associated with biofilm? METHODS: Three clinical isolates, S aureus, S epidermidis, and P aeruginosa were cultured to create biofilm on surgical grade stainless steel. At least 52 samples were analyzed per group using a FT-NIR spectrometer. Multivariate and principal component analyses were performed on the spectral data to allow for modeling and identification of the bacterial species. RESULTS: Spectral analysis was able to correctly identify 86% (37/43) of S aureus, 89% (16/18) of S epidermidis, and 70% (28/40) of P aeruginosa samples with minimal error. Overall, models developed using spectral data preprocessed using a combination of standard normal variant and first derivative transformations performed much better than models developed with the raw spectral data in discriminating between the three classes of bacteria because of its low Type 1 error and large intermodel distinction. CONCLUSIONS: The use of spectroscopic methods to identify and classify bacterial biofilms on orthopaedic implant material is possible and improves with advanced modeling that can be obtained rapidly with little error. The sensitivity for identification was 97% for S aureus (95% CI, 88-99%), 100% for S epidermidis (95% CI, 95-100%), and 77% for P aeruginosa (95% CI, 65-86%). The specificity of the S aureus was 86% (95% CI, 3-93%), S epidermidis was 89% (95% CI, 67-97%), and P aeruginosa was 70% (95% CI, 55-82%). CLINICAL RELEVANCE: This technique of spectral data acquisition and advanced modeling should continue to be explored as a method for bacterial biofilm identification. A spectral databank of bacterial and potentially contaminating tissues should be acquired initially through an in vivo animal model and quickly transition to explanted devices and the clinical arena. PMID- 26265210 TI - Adult-onset myoclonus ataxia associated with the mitochondrial m.8993T>C "NARP" mutation. PMID- 26265209 TI - Body mass index association with functional gastrointestinal disorders: differences between genders. Results from a study in a tertiary center. AB - BACKGROUND: Obesity is considered as a risk factor for many functional gastrointestinal disorders. The aim of the study was to evaluate if functional digestive disorders are associated with specific body mass index groups and gender. METHODS: A total of 1074 patients (50.3 +/- 16.5 years, 67 % females) filled out a standard Rome III questionnaire (79 % acceptance rate). The patients were assigned to five groups according to their body mass index: underweight (6 %), normal (49 %), overweight (28 %), obese (12 %), and morbidly obese (5 %). Data analysis was performed using multinomial logistic regression; subjects with the normal weight were the reference group. RESULTS: Patients presented specific demographic and clinical characteristics according to the weight groups. Underweight patients were younger (p < 0.001), and presented a female predominance (p = 0.006), dysphagia (p = 0.013) and soiling (p = 0.021). Overweight patients were older (p = 0.001), and reported more frequently globus (p = 0.001), regurgitation (p = 0.004), postprandial distress syndrome (p = 0.009). Obese patients reported more frequently regurgitation (p < 0.001). Morbid obese patients reported dyspepsia (p = 0.046). In patients, the odds of regurgitation increased with body mass index from underweight to obesity, but not when compared to morbid obesity. The probability of globus and regurgitation increased with body mass index and presented a steeper increase in females. CONCLUSIONS: In patients with functional gastrointestinal disorders, globus and regurgitation are associated with body mass index, mainly in female patients. PMID- 26265211 TI - Chromosomal copy number alterations for associations of ductal carcinoma in situ with invasive breast cancer. AB - INTRODUCTION: Screening mammography has contributed to a significant increase in the diagnosis of ductal carcinoma in situ (DCIS), raising concerns about overdiagnosis and overtreatment. Building on prior observations from lineage evolution analysis, we examined whether measuring genomic features of DCIS would predict association with invasive breast carcinoma (IBC). The long-term goal is to enhance standard clinicopathologic measures of low- versus high-risk DCIS and to enable risk-appropriate treatment. METHODS: We studied three common chromosomal copy number alterations (CNA) in IBC and designed fluorescence in situ hybridization-based assay to measure copy number at these loci in DCIS samples. Clinicopathologic data were extracted from the electronic medical records of Stanford Cancer Institute and linked to demographic data from the population-based California Cancer Registry; results were integrated with data from tissue microarrays of specimens containing DCIS that did not develop IBC versus DCIS with concurrent IBC. Multivariable logistic regression analysis was performed to describe associations of CNAs with these two groups of DCIS. RESULTS: We examined 271 patients with DCIS (120 that did not develop IBC and 151 with concurrent IBC) for the presence of 1q, 8q24 and 11q13 copy number gains. Compared to DCIS-only patients, patients with concurrent IBC had higher frequencies of CNAs in their DCIS samples. On multivariable analysis with conventional clinicopathologic features, the copy number gains were significantly associated with concurrent IBC. The state of two of the three copy number gains in DCIS was associated with a risk of IBC that was 9.07 times that of no copy number gains, and the presence of gains at all three genomic loci in DCIS was associated with a more than 17-fold risk (P = 0.0013). CONCLUSIONS: CNAs have the potential to improve the identification of high-risk DCIS, defined by presence of concurrent IBC. Expanding and validating this approach in both additional cross sectional and longitudinal cohorts may enable improved risk stratification and risk-appropriate treatment in DCIS. PMID- 26265213 TI - The partly Aalen's model for recurrent event data with a dependent terminal event. AB - Recurrent event data are commonly observed in biomedical longitudinal studies. In many instances, there exists a terminal event, which precludes the occurrence of additional repeated events, and usually there is also a nonignorable correlation between the terminal event and recurrent events. In this article, we propose a partly Aalen's additive model with a multiplicative frailty for the rate function of recurrent event process and assume a Cox frailty model for terminal event time. A shared gamma frailty is used to describe the correlation between the two types of events. Consequently, this joint model can provide the information of temporal influence of absolute covariate effects on the rate of recurrent event process, which is usually helpful in the decision-making process for physicians. An estimating equation approach is developed to estimate marginal and association parameters in the joint model. The consistency of the proposed estimator is established. Simulation studies demonstrate that the proposed approach is appropriate for practical use. We apply the proposed method to a peritonitis cohort data set for illustration. PMID- 26265212 TI - Myosin VI and cardiomyopathy: Left ventricular hypertrophy, fibrosis, and both cardiac and pulmonary vascular endothelial cell defects in the Snell's waltzer mouse. AB - In mice and humans, loss of myosin VI (Myo6) function results in deafness, and certain Myo6 mutations also result in cardiomyopathies in humans. The current studies have utilized the Snell's waltzer (sv) mouse (a functional null mutation for Myo6) to determine if this mouse also exhibits cardiac defects and thus used to determine the cellular and molecular basis for Myo6-associated heart disease. Myo6 is expressed in mouse heart where it is predominantly expressed in vascular endothelial cells (VECs) based on co-localization with the VEC cell marker CD31. Sv/sv heart mass is significantly greater than that of sv/+ littermates, a result of left ventricle hypertrophy. The left ventricle of the sv/sv exhibits extensive fibrosis, both interstitial and perivascular, based on histologic staining, and immunolocalization of several markers for fibrosis including fibronectin, collagen IV, and the fibroblast marker vimentin. Myo6 is also expressed in lung VECs but not in VECs of intestine, kidney, or liver. Sv/sv lungs exhibit increased periaveolar fibrosis and enlarged air sacs. Electron microscopy of sv/sv cardiac and lung VECs revealed abnormal ultrastructure, including luminal protrusions and increased numbers of cytoplasmic vesicles. Previous studies have shown that loss of function of either Myo6 or its adaptor binding partner synectin/GIPC results in impaired arterial development due to defects in VEGF signaling. However, examination of synectin/GIPC-/- heart revealed no fibrosis or significantly altered VEC ultrastructure, suggesting that the cardiac and lung defects observed in the sv/sv mouse are not due to Myo6 function in arterial development. PMID- 26265214 TI - Survival outcomes of supportive care versus dialysis therapies for elderly patients with end-stage kidney disease: A systematic review and meta-analysis. AB - AIM: Elderly people comprise a large and growing proportion of the global dialysis population. Regional differences in rates of dialysis in the elderly suggest multiple factors influence treatment decision-making including beliefs about the relative benefits and harms of dialysis and supportive (non-dialysis) care. We therefore systematically reviewed the literature reporting survival of elderly patients treated with either treatment pathway. METHODS: Systematic review and meta-analysis of cohort studies or randomized controlled trials identified in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials published before July 2014. Survival by treatment modality was calculated. Subgroup analyses by study design, study size, patient age and cohort era were conducted. RESULTS: Eighty-nine studies published between 1976 and 2014 reported on 294 921 elderly end-stage kidney disease (ESKD) patients. There was a paucity of data for supportive care (724 patients or 0.2% of the total patients) and supportive care studies were susceptible to lead-time bias. One-year survival for elderly patients treated with undifferentiated dialysis was 73.0% (95% confidence interval (CI) 66.3-79.7%), 78.4% (95% CI 75.2-81.6) for haemodialysis and 77.9% (95% CI 73.8-81.9) for peritoneal dialysis. Supportive care patients had a 1-year survival of 70.6% (95% CI 63.3-78.0%). Residual heterogeneity remained within individual treatment modalities despite subgroup analyses. CONCLUSIONS: While the available literature demonstrates a broadly similar 1-year survival in elderly ESKD patients, it does not allow a confident estimate of the relative survival benefits of dialysis or supportive care. This uncertainty needs urgent attendance by further prospective data, which avoid bias and allow comparisons of quality of life and survival. PMID- 26265215 TI - Nanomolar aluminum induces expression of the inflammatory systemic biomarker C reactive protein (CRP) in human brain microvessel endothelial cells (hBMECs). AB - C-reactive protein (CRP; also known as pentraxin 1, PTX1), a 224 amino acid soluble serum protein organized into a novel pentameric ring-shaped structure, is a highly sensitive pathogenic biomarker for systemic inflammation. High CRP levels are found in practically every known inflammatory state, and elevated CRP levels indicate an increased risk for several common age-related human degenerative disorders, including cardiovascular disease, cancer, diabetes, and Alzheimer's disease (AD). While the majority of CRP is synthesized in the liver for secretion into the systemic circulation, it has recently been discovered that an appreciable amount of CRP is synthesized in highly specialized endothelial cells that line the vasculature of the brain and central nervous system (CNS). These highly specialized cells, the major cell type lining the human CNS vasculature, are known as human brain microvessel endothelial cells (hBMECs). In the current pilot study we examined (i) CRP levels in human serum obtained from AD and age-matched control patients; and (ii) analyzed the effects of nanomolar aluminum sulfate on CRP expression in primary hBMECs. The three major findings in this short communication are: (i) that CRP is up-regulated in AD serum; (ii) that CRP serum levels increased in parallel with AD progression; and (iii) for the first time show that nanomolar aluminum potently up-regulates CRP expression in hBMECs to many times its 'basal abundance'. The results suggest that aluminum induced CRP may in part contribute to a pathophysiological state associated with a chronic systemic inflammation of the human vasculature. PMID- 26265216 TI - Extensive Four-Dimensional Chaos in a Mesoscopic Model of the Electroencephalogram. AB - BACKGROUND: In a previous work (Dafilis et al. in Chaos 23(2):023111, 2013), evidence was presented for four-dimensional chaos in Liley's mesoscopic model of the electroencephalogram. The study was limited to one parameter set of the model equations. FINDINGS: In this report we expand that result by presenting evidence for the extension of four-dimensional chaotic behavior to a large area of the biologically admissible parameter space. A two-parameter bifurcation analysis highlights the complexity of the dynamical landscape involved in the creation of such chaos. CONCLUSIONS: The extensive presence of high-order chaos in a well established physiological model of electrorhythmogenesis further emphasizes the applicability and relevance of mean field mesoscopic models in the description of brain activity at theoretical, experimental, and clinical levels. PMID- 26265217 TI - A Simple Mechanism for Beyond-Pairwise Correlations in Integrate-and-Fire Neurons. AB - The collective dynamics of neural populations are often characterized in terms of correlations in the spike activity of different neurons. We have developed an understanding of the circuit mechanisms that lead to correlations among cell pairs, but little is known about what determines the population firing statistics among larger groups of cells. Here, we examine this question for a simple, but ubiquitous, circuit feature: common fluctuating input arriving to spiking neurons of integrate-and-fire type. We show that this leads to strong beyond-pairwise correlations-that is, correlations that cannot be captured by maximum entropy models that extrapolate from pairwise statistics-as for earlier work with discrete threshold crossing (dichotomous Gaussian) models. Moreover, we find that the same is true for another widely used, doubly stochastic model of neural spiking, the linear-nonlinear cascade. We demonstrate the strong connection between the collective dynamics produced by integrate-and-fire and dichotomous Gaussian models, and show that the latter is a surprisingly accurate model of the former. Our conclusion is that beyond-pairwise correlations can be both broadly expected and possible to describe by simplified (and tractable) statistical models. PMID- 26265218 TI - A cohort study: temporal trends in prevalence of antecedents, comorbidities and mortality in Aboriginal and non-Aboriginal Australians with first heart failure hospitalization, 2000-2009. AB - BACKGROUND/OBJECTIVES: Little is known about trends in risk factors and mortality for Aboriginal Australians with heart failure (HF). This population-based study evaluated trends in prevalence of risk factors, 30-day and 1-year all-cause mortality following first HF hospitalization among Aboriginal and non-Aboriginal Western Australians in the decade 2000-2009. METHODS: Linked-health data were used to identify patients (20-84 years), with a first-ever HF hospitalization. Trends in demographics, comorbidities, interventions and risk factors were evaluated. Logistic and Cox regression models were fitted to test and compare trends over time in 30-day and 1-year mortality. RESULTS: Of 17,379 HF patients, 1,013 (5.8%) were Aboriginal. Compared with 2000-2002, the prevalence (as history) of myocardial infarction and hypertension increased more markedly in 2006-2009 in Aboriginal (versus non-Aboriginal) patients, while diabetes and chronic kidney disease remained disproportionately higher in Aboriginal patients. Risk factor trends, including the Charlson comorbidity index, increased over time in younger Aboriginal patients. Risk-adjusted 30-day mortality did not change over the decade in either group. Risk-adjusted 1-year mortality (in 30-day survivors) was non-significantly higher in Aboriginal patients in 2006-2008 compared with 2000-2002 (hazard ratio (HR) 1.44; 95% CI 0.85-2.41; p-trend = 0.47) whereas it decreased in non-Aboriginal patients (HR 0.87; 95% CI 0.78-0.97; p-trend = 0.01). CONCLUSIONS: Between 2000 and 2009, the prevalence of HF antecedents increased and remained disproportionately higher in Aboriginal (versus non-Aboriginal) HF patients. Risk-adjusted 1-year mortality did not improve in Aboriginal patients over the period in contrast with non-Aboriginal patients. These findings highlight the need for better prevention and post-HF care in Aboriginal Australians. PMID- 26265219 TI - Diagnosis of primary secretory otitis media in the cavalier King Charles spaniel. AB - BACKGROUND: Primary secretory otitis media (PSOM) is a disease reported in the cavalier King Charles spaniel (CKCS). The diagnosis of PSOM has been made based only on visualization of a bulging tympanic membrane and mucus in the middle ear post-myringotomy. No additional tests have been evaluated for the diagnosis of PSOM; CKCSs with early disease may have been missed. HYPOTHESIS/OBJECTIVES: The objective of this study was to compare otoscopy, tympanometry, pneumotoscopy and tympanic bulla ultrasonography, using computed tomography (CT) as the gold standard for the diagnosis of PSOM in the CKCS. ANIMALS: Sixty CKCSs with clinical signs suggestive of PSOM. METHODS: Otoscopy, CT scan, tympanic bulla ultrasonography, tympanometry and pneumotoscopy were performed; those CKCSs with a soft tissue density in the middle ear identified on CT had a myringotomy and middle ear flush. RESULTS: Forty-three (72%) CKCSs had PSOM (30 bilateral, 13 unilateral). A large bulging pars flaccida was identified in only those CKCS with PSOM (specificity of 100%); however, only 21 of 73 ears with PSOM had a large bulging pars flaccida (sensitivity of 29%). Sensitivity and specificity for tympanometry, pneumotoscopy and tympanic bulla ultrasonography were (84%, 47%), (75%, 79%) and (67%, 47%), respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Based on these results a large bulging pars flaccida indicates the presence of PSOM, whereas a flat pars flaccida may be present in CKCS that have PSOM as well as those that do not. In CKCSs with a flat pars flaccida none of the above diagnostic tests can be recommended in place of CT scan for the diagnosis of PSOM. PMID- 26265220 TI - Prolongation of antibiotic treatment for cystic fibrosis pulmonary exacerbations. AB - BACKGROUND: Pulmonary exacerbations frequently lead to an irrevocable loss of lung function in cystic fibrosis (CF) patients. Although extended antibiotic duration has not been shown to be associated with improved outcomes in CF overall, it is not known whether there is a subset of patients who may benefit from longer treatment courses. METHODS: This was a retrospective cohort study, using the Toronto CF Database from 1997 to 2012, of CF individuals with pulmonary exacerbations requiring intravenous antibiotic treatment. We investigated factors associated with improvement in forced expiratory volume in 1 second (FEV1) in patients treated with <=14 days and >14 days of antibiotic treatment. RESULTS: A total of 538 pulmonary exacerbations in 253 patients were used for these analysis; 39% of these exacerbations fully recovered lung function at follow-up. Exacerbations were more frequently treated with >14 days of antibiotics in older patients with lower FEV1 at exacerbation and higher rates of B. cepacia complex infections. Subjects with exacerbations treated for >14 days had a significantly greater increase in FEV1 from day 14 to follow up compared to those with <=14 days (p<0.001). On multivariable analysis, smaller changes from days 0 to 14 of antibiotics and treatment duration>14 days were associated with greater increases in FEV1 from day 14 to follow-up. In those who received >14 days of antibiotic therapy, smaller improvements in FEV1 change from day 0 to 14 and younger age at exacerbation were significantly associated with a greater FEV1 response from day 14 to end of treatment. Antibiotic treatment >14 days was not associated with longer time to subsequent exacerbation. CONCLUSIONS: This study highlights that in the treatment of pulmonary exacerbations, maximum lung function is not achieved within 14 days in all patients, and that there is continued improvement beyond this period. PMID- 26265221 TI - Interpersonal communication as an agent of normative influence: a mixed method study among the urban poor in India. AB - BACKGROUND: Although social norms are thought to play an important role in couples' reproductive decisions, only limited theoretical or empirical guidance exists on how the underlying process works. Using the theory of normative social behavior (TNSB), through a mixed-method design, we investigated the role played by injunctive norms and interpersonal discussion in the relationship between descriptive norms and use of modern contraceptive methods among the urban poor in India. METHODS: Data from a household survey (N = 11,811) were used to test the underlying theoretical propositions, and focus group interviews among men and women were then conducted to obtain more in-depth knowledge about decision-making processes related to modern contraceptive use. RESULTS: Spousal influence and interpersonal communication emerged as key factors in decision-making, waning in the later years of marriage, and they also moderated the influence of descriptive norms on behaviors. Norms around contraceptive use, which varied by parity, are rapidly changing with the country's urbanization and increased access to health information. CONCLUSION: Open interpersonal discussion, community norms, and perspectives are integral in enabling women and couples to use modern family planning to meet their current fertility desires and warrant sensitivity in the design of family planning policy and programs. PMID- 26265223 TI - Ramucirumab for Colon Cancer and the Problem of Rising Prices Independent of Benefits. PMID- 26265222 TI - Supporting Option B+ scale up and strengthening the prevention of mother-to-child transmission cascade in central Malawi: results from a serial cross-sectional study. AB - BACKGROUND: We established Safeguard the Family (STF) to support Ministry of Health (MoH) scale-up of universal antiretroviral therapy (ART) for HIV-infected pregnant and breastfeeding women (Option B+) and to strengthen the prevention of mother-to-child transmission (PMTCT) cascade from HIV testing and counseling (HTC) through maternal ART provision and post-delivery early infant HIV diagnosis (EID). To these ends, we implemented the following interventions in 5 districts: 1) health worker training and mentorship; 2) couples' HTC and male partner involvement; 3) women's psychosocial support groups; and 4) health and laboratory system strengthening for EID. METHODS: We conducted a serial cross-sectional study using facility-level quarterly (Q) program data and individual-level infant HIV-1 DNA PCR data to evaluate STF performance on PMTCT indicators for project years (Y) 1 (April-December 2011) through 3 (January-December 2013), and compared these results to national averages. RESULTS: Facility-level uptake of HTC, ART, infant nevirapine prophylaxis, and infant DNA PCR testing increased significantly from quarterly baselines of 66 % (n/N = 32,433/48,804), 23 % (n/N = 442/1,958), 1 % (n/N = 10/1,958), and 52 % (n/N = 1,385/2,644) to 87 % (n/N = 39,458/45,324), 96 % (n/N = 2,046/2,121), 100 % (n/N = 2,121/2,121), and 62 % (n/N = 1,462/2,340), respectively, by project end (all p < 0.001). Quarterly HTC, ART, and infant nevirapine prophylaxis uptake outperformed national averages over years 2-3. While transitioning EID laboratory services to MoH, STF provided first time HIV-1 DNA PCR testing for 2,226 of 11,261 HIV-exposed infants (20 %) tested in the MoH EID program in STF districts from program inception (Y2) through Y3. Of these, 78 (3.5 %) tested HIV-positive. Among infants with complete documentation (n = 608), median age at first testing decreased from 112 days (interquartile range, IQR: 57-198) in Y2 to 76 days (IQR: 46-152) in Y3 (p < 0.001). During Y3 (only year with national data for comparison), non significantly fewer exposed infants tested HIV-positive (3.6 %) at first testing in STF districts than nationally (4.1 %) (p = 0.4). CONCLUSIONS: STF interventions, integrated within the MoH Option B+ program, achieved favorable HTC, maternal ART, infant prophylaxis, and EID services uptake, and a low proportion of infants found HIV-infected at first DNA PCR testing. Continued investments are needed to strengthen the PMTCT cascade, particularly around EID. PMID- 26265224 TI - What Plagues Cancer: Does It Spread? PMID- 26265225 TI - Considering Efficacy and Cost, Where Does Ramucirumab Fit in the Management of Metastatic Colorectal Cancer? PMID- 26265226 TI - Is the endocrine research pipeline broken? A systematic evaluation of the Endocrine Society clinical practice guidelines and trial registration. AB - BACKGROUND: Very low quality (VLQ) evidence translates into very low confidence in the balance of risk and benefits based on the estimates drawn from the body of evidence. Consequently, this assessment highlights gaps in the research evidence, i.e. knowledge gaps, for important clinical questions. In this way, expert guideline panels identify priority knowledge gaps that, arguably, should inform the research agenda and prioritize scarce research economical resources. The extent to which the research agenda reflects the knowledge gaps identified in clinical practice guidelines is unknown. METHODS: A systematic evaluation of the Endocrine Society (ES) clinical practice guidelines portfolio from 2008 to 2014 was conducted with the objectives to identify (1) recommendations in the ES clinical practice guidelines based on VLQ evidence reflecting knowledge gaps in endocrinology, and (2) active research designed to address these gaps by searching the clinical trial registry, clinicaltrials.gov, using terms describing patients (diseases), interventions, comparison, and outcomes. RESULTS: In 25 ES guidelines, we found 660 recommendations, of which 131 (20 %) were supported by VLQ evidence. Clinical trialists are attempting to answer 28 (21 %) of these knowledge gaps by performing 69 clinical trials. CONCLUSION: The research enterprise is addressing one in five knowledge gaps identified in clinical practice recommendations in endocrinology. These findings suggest an inefficiency in the allocation of very scarce research economical resources. Linking the research agenda to evidence gaps in clinical practice guidelines may improve both the efficiency of the research enterprise and the translation of evidence into more confident clinical practice. PMID- 26265227 TI - Simultaneous treatment of pterygium complicated with conjunctivochalasis: analysis of pterygium excision and conjunctival autotransplantation combined with sclera fixation. AB - BACKGROUND: This prospective study investigated the safety and efficacy of a therapeutic method of treating pterygium complicated with conjunctivochalasis, using pterygium excision and conjunctival autotransplantation combined with sclera fixation, followed by therapeutic contact lens application. METHODS: Fifty seven patients (83 eyes) diagnosed as pterygium complicated with conjunctivochalasis, at our hospital from July 2011 to June 2012, were selected. Patients were treated with pterygium excision and conjunctival autotransplantation combined with sclera fixation surgery, then therapeutic bandage contact lenses were applied. The efficacy of simultaneous surgery was evaluated based on vision changes, tear dynamics, and other complications. Histopathological changes were investigated on removed bulbar conjunctival tissue, using hematoxylin eosin (HE) and Masson's trichrome staining. RESULTS: (1) Three months after the operation, the success of simultaneous surgery in the treatment of pterygium was 97.6 %, and the recurrence was 2.4 %. Based on subjective evaluation, the success of the simultaneous treatment of conjunctivochalasis was 95.2 %, and failure was 4.8 %. Based on objective evaluation, the success rate was 94.0 % and the recurrence rate was 6.0 %. (2) Visual acuity of the 83 eyes was significantly improved after surgery, and was statistically significant (X 2 = 10.29, P < 0.05). (3) Three months after surgery, the height and integrity of the tear meniscus, tear film break-up time, and chloramphenicol test results of the 83 eyes were significantly improved and there was a statistically significant difference (X 2 the height and integrity of tear meniscus = 147.24, X 2 tear film break-up time = 81.17, X 2 chloramphenicol test = 17.41, P < 0.01). (4) Complications after the operation such as granulation hyperplasia, constrictive fornix, oculomotor defect, and other complications were not observed. (5) Pathological observations, using HE and Masson's trichrome staining of removed bulbar conjunctival tissue, showed several pathological changes, including obvious squamous epithelial hyperplasia, parakeratosis, basal cell pigmentation, lamina propria hemorrhage, infiltration of lymphocytes, and reduction of elastic fibers and collagen fibers. CONCLUSION: Pterygium excision and conjunctival autotransplantation, combined with sclera fixation followed by therapeutic contact lens use was safe, effective, and suitable for simultaneous treatment of pterygium complicated with conjunctivochalasis. PMID- 26265228 TI - Advanced neuroimaging of cerebral palsy following extremely preterm birth. PMID- 26265229 TI - Evaluation of infectious bursal disease virus stability at different conditions of temperature and pH. AB - Infectious bursal disease (IBD) is one of the highly pathogenic viral diseases of poultry. The disease poses a serious threat to the economy of many developing countries where agriculture serves as the primary source of national income. Infectious bursal disease virus (IBDV) belongs to the family Birnaviridae. The IBDV is well characterized to cause immunosuppression in poultry. The live attenuated vaccine is the only way to protect the chickens from IBDV infection. The ineffectiveness of vaccine is one of the major causes of IBDV outbreaks in field condition. In the present study, we discuss briefly about the biology of IBDV genome and its proteins under different conditions of temperature and pH in order to evaluate its infectivity under adverse physical conditions. Our results indicate that the IBDV is non-infective above 42 degrees C and unstable above 72 degrees C. However, the change in pH does not significantly contribute to the IBDV stability. The study will be useful in estimating an optimum storage condition for IBDV vaccines without causing any deterioration in its viability and effectiveness. PMID- 26265230 TI - Funding for medical education research should not be based on anticipated improvements to patient care. PMID- 26265231 TI - Genetic and platelet function testing of antiplatelet therapy for percutaneous coronary intervention: the ARCTIC-GENE study. AB - BACKGROUND: The ARCTIC study randomized 2440 patients scheduled for stent implantation to a strategy of platelet function monitoring with drug adjustment in patients who had a poor response to antiplatelet therapy or to a conventional strategy without monitoring and drug adjustment. No significant improvement in clinical outcomes with platelet function monitoring was observed. OBJECTIVE: The purpose of this study is to assess the relationships between CYP2C19 genotypes, clopidogrel pharmacodynamic response, and clinical outcome. METHODS AND RESULTS: In the ARCTIC-GENE study, 1394 patients were genotyped for loss- and gain-of function CYP2C19 alleles. Randomization of treatment strategy was well balanced. Slow metabolizers identified as carriers of at least one loss-of-function allele CYP2C19*2 (n = 459) were more likely poor responders at randomization (41.6 vs. 31.6%, p = 0.0112) and 14 days later (23.8 vs. 10.4%, p < 0.0001) and more frequently on prasugrel (11.5 vs. 8.1%, p = 0.039) as compared with rapid metabolizers (n = 935). Intensification of antiplatelet treatment did not differ between slow and rapid metabolizers according to the study algorithm based on platelet function only. The primary study outcome defined as the composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization 1 year after stent implantation did not differ between slow and rapid metabolizers (HR 0.988, 95% CI [0.812;1.202], p = 0.90). Likewise, the primary safety outcome did not differ between rapid and slow metabolizer phenotype. CONCLUSIONS: The genetic clopidogrel profile was a good marker of platelet function response on clopidogrel but was not related to clinical outcome suggesting that the genetic added little to the pharmacodynamic information used in the study to adjust antiplatelet therapy. ClinicalTrials.gov: NCT00827411. PMID- 26265232 TI - Oral and inhaled p38 MAPK inhibitors: effects on inhaled LPS challenge in healthy subjects. AB - BACKGROUND: Inhaled LPS causes neutrophilic airway inflammation in healthy subjects. We compared the effects of p38 MAPK inhibitors and fluticasone propionate on the LPS response. METHODS: Three randomised, double-blind, placebo controlled, single dose crossover studies were performed. Active treatments were the oral p38 MAPK inhibitor PH-797804 30 mg (study 1), PH-797804 30 mg and the inhaled p38 MAPK inhibitor PF-03715455 20 mg (study 2) and inhaled fluticasone propionate 500 MUg (study 3). The primary endpoint was sputum neutrophil percentage. RESULTS: Sputum neutrophil percentage post-LPS challenge was significantly inhibited (15.1 and 15.3% reduction) by PH-797804 compared to placebo in studies 1 and 2 (p = 0.0096 and 0.0001, respectively), and by PF 03715455 (8.0% reduction, p = 0.031); fluticasone propionate had no effect. PH 797804 significantly inhibited the increase in inflammatory mediators (IL-6, MCP 1, MIP1beta and CC16) in sputum supernatant, while PF-03715455 had no effect. PH 797804 and PF-03715455 both inhibited IL-6, MCP-1, MIP1beta, CC16 and CRP levels in plasma, with PH-797804 having greater effects. Fluticasone propionate had no effect on sputum supernatant or plasma biomarkers. CONCLUSIONS: PH-797804 had the greatest impact on neutrophilic airway inflammation. Oral administration of p38 MAPK inhibitors may optimise pulmonary anti-inflammatory effects. PMID- 26265233 TI - Trefoil factors: Gastrointestinal-specific proteins associated with gastric cancer. AB - Trefoil factor family (TFF), composed of TFF1, TFF2, and TFF3, is a cluster of secreted peptides characterized by trefoil domain (s) and C-terminal dimerization domain. TFF1, a gastric tumor suppressor, is a single trefoil peptide originally detected in breast cancer cell lines but expressed mainly in the stomach; TFF2, a candidate of gastric cancer suppressor with two trefoil domains, is abundant in the stomach and duodenal Brunner's glands; and TFF3 is another single trefoil peptide expressed throughout the intestine which can promote the development of gastric carcinoma. According to multiple studies, TFFs play a regulatory function in the mammals' digestive system, namely in mucosal protection and epithelial cell reconstruction, tumor suppression or promotion, signal transduction and the regulation of proliferation and apoptosis. Action mechanisms of TFFs remain unresolved, but the recent demonstration of a GKN (gastrokine) 2-TFF1 heterodimer implicates structural and functional interplay with gastrokines. This review aims to encapsulate the structural and biological characteristics of TFF. PMID- 26265234 TI - Investigation of MDA-LDL (malondialdehyde-modified low-density lipoprotein) as a prognostic marker for coronary artery disease in patients with type 2 diabetes mellitus. AB - BACKGROUND: Although increased circulating levels of malondialdehyde-modified low density lipoprotein (MDA-LDL) are associated with coronary artery disease (CAD), there is no direct evidence that increased MDA-LDL is a prognostic factor for CAD. METHODS: Forty-two patients (20 diabetic and 22 non-diabetic patients) who underwent percutaneous coronary intervention (PCI) were enrolled, and their baseline MDA-LDL levels were determined by immunoassay. Follow-up coronary angiography was performed at 2 to 7 months post-PCI. The patients were then divided into 2 groups, with in-stent restenosis (ISR) (n=13) and without ISR (n=29), and the baseline MDA-LDL levels were compared. We also studied 34 diabetics with CAD for up to 57 months until the onset of the next coronary event. RESULTS: In the diabetic patients, the mean MDA-LDL level was significantly higher in those with ISR than in those without ISR (151+/-61 vs. 90+/-26 U/l, p=0.010). A baseline MDA-LDL value of 110 U/l for differentiating between diabetics with and without ISR was defined as the cut-off value. Kaplan Meier analysis demonstrated that a circulating MDA-LDL of >= 110 U/l correlated significantly with a higher prevalence of cardiac events than MDA-LDL <110 U/l (p=0.032). CONCLUSIONS: Circulating MDA-LDL is a useful prognostic marker for future cardiac event in diabetic patients with CAD. PMID- 26265235 TI - Rash in lapatinib-treated patients is not associated with human leukocyte antigen polymorphisms. AB - Rash is a common side effect of lapatinib treatment. Since human leukocyte antigen (HLA) alleles have been implicated in multiple drug-induced cutaneous reactions, this study investigated the association of HLA alleles with lapatinib induced rash. 1191 participants from a large lapatinib monotherapy trial underwent HLA genotyping, and allele carriage frequencies between rash cases and controls were compared. This analysis had adequate power to detect an association of common HLA alleles with rash, similar to those reported previously. No HLA alleles were significantly associated with lapatinib-induced rash, including the previously identified lapatinib hepatotoxicity biomarker HLA-DRB1*07:01 (p = 0.87). The present study is consistent with the view that lapatinib-induced rash is not the consequence of HLA-restricted, immune-mediated mechanisms. PMID- 26265236 TI - A Context-Aware Interactive Health Care System Based on Ontology and Fuzzy Inference. AB - In the present society, most families are double-income families, and as the long term care is seriously short of manpower, it contributes to the rapid development of tele-homecare equipment, and the smart home care system gradually emerges, which assists the elderly or patients with chronic diseases in daily life. This study aims at interaction between persons under care and the system in various living spaces, as based on motion-sensing interaction, and the context-aware smart home care system is proposed. The system stores the required contexts in knowledge ontology, including the physiological information and environmental information of the person under care, as the database of decision. The motion sensing device enables the person under care to interact with the system through gestures. By the inference mechanism of fuzzy theory, the system can offer advice and rapidly execute service, thus, implementing the EHA. In addition, the system is integrated with the functions of smart phone, tablet PC, and PC, in order that users can implement remote operation and share information regarding the person under care. The health care system constructed in this study enables the decision making system to probe into the health risk of each person under care; then, from the view of preventive medicine, and through a composing system and simulation experimentation, tracks the physiological trend of the person under care, and provides early warning service, thus, promoting smart home care. PMID- 26265237 TI - A Kinect-Based System for Lower Limb Rehabilitation in Parkinson's Disease Patients: a Pilot Study. AB - This work brings together the emerging virtual reality techniques and the natural user interfaces to offer new possibilities in the field of rehabilitation. We have designed a rehabilitation game based on a low cost device (Microsoft Kinect(TM)) connected to a personal computer. It provides patients having Parkinson's Disease (PD) with a motivating way to perform several motor rehabilitation exercises to improve their rehabilitation. The experiment was tested on seven Parkinson's Disease patients and results demonstrated significant improvements in completion time score and in the 10 Meters Walk Test score. Nevertheless, additional research is needed to determine if this type of training has a long-term impact. Both the device and protocol were well accepted by subjects, being safe and easy to use. We conclude that our work provides a simple and suitable tool resulting in a more enriching rehabilitation process where motivation is highly encouraged in PD patients. Feedback coming from participants corroborate the hypothesis that the system can be applied not only in clinical rehabilitation centers but at home. PMID- 26265238 TI - On the Effect of Previous Technological Experience on the Usability of a Virtual Rehabilitation Tool for the Physical Activation and Cognitive Stimulation of Elders. AB - We present and discuss our findings on the identified causes for the differences of the results of two usability studies on the borrowed use of Gesture Therapy, a virtual rehabilitation tool for the cognitive stimulation and physical activation of elders. The studies focused on usability aspects including perceived usefulness, ease of use, intention of use and user experience. In the first study, we used self-report techniques to gather data, and found that previous technological experience had a significant effect on the perceived anxiety of elders; while on the second study, we used indirect observation techniques to gather data, and found that previous technological experience had a significant effect on the perceived enjoyment of elders. After a further analysis of the video recordings of the playing sessions, we identified that elders developed two different approaches to their using the application (explore-and-learn and score and-compete), which could be related to their previous technological experience, and explain the identified differences. We observed that in the presence of problems, the response of participants was different depending on the adopted behavior. Based on this evidence, we distilled a set of preliminary guidelines to foster or inhibit certain behaviors and outcomes related to the effect of previous experience that were observed during our evaluation studies of virtual tools for the cognitive stimulation and physical activation of the elderly. PMID- 26265239 TI - Perioperative Smartphone Apps and Devices for Patient-Centered Care. AB - Smartphones have grown in ubiquity and computing power, and they play an ever increasing role in patient-centered health care. The "medicalized smartphone" not only enables web-based access to patient health resources, but also can run patient-oriented software applications and be connected to health-related peripheral devices. A variety of patient-oriented smartphone apps and devices are available for use to facilitate patient-centered care throughout the continuum of perioperative care. Ongoing advances in smartphone technology and health care apps and devices should expand their utility for enhancing patient-centered care in the future. PMID- 26265240 TI - Impact of inhalational exposure to ethanol fuel on the pharmacokinetics of verapamil, ibuprofen and fluoxetine as in vivo probe drugs for CYP3A, CYP2C and CYP2D in rats. AB - Occupational toxicology and clinical pharmacology integration will be useful to understand potential exposure-drug interaction and to shape risk assessment strategies in order to improve occupational health. The aim of the present study was to evaluate the effect of exposure to ethanol fuel on in vivo activities of cytochrome P450 (CYP) isoenzymes CYP3A, CYP2C and CYP2D by the oral administration of the probe drugs verapamil, ibuprofen and fluoxetine. Male Wistar rats exposed to filtered air or to 2000 ppm ethanol in a nose-only inhalation chamber during (6 h/day, 5 days/week, 6 weeks) received single oral doses of 10 mg/kg verapamil or 25 mg/kg ibuprofen or 10 mg/kg fluoxetine. The enantiomers of verapamil, norverapamil, ibuprofen and fluoxetine in plasma were analyzed by LC-MS/MS. The area under the curve plasma concentration versus time extrapolated to infinity (AUC(0-infinity)) was calculated using the Gauss Laguerre quadrature. Inhalation exposure to ethanol reduces the AUC of both verapamil (approximately 2.7 fold) and norverapamil enantiomers (>2.5 fold), reduces the AUC(0-infinity) of (+)-(S)-IBU (approximately 2 fold) and inhibits preferentially the metabolism of (-)-(R)-FLU. In conclusion, inhalation exposure of ethanol at a concentration of 2 TLV-STEL (6 h/day for 6 weeks) induces CYP3A and CYP2C but inhibits CYP2D in rats. PMID- 26265241 TI - Retinal vessel segmentation using multi-scale textons derived from keypoints. AB - This paper presents a retinal vessel segmentation algorithm which uses a texton dictionary to classify vessel/non-vessel pixels. However, in contrast to previous work where filter parameters are learnt from manually labelled image pixels our filter parameters are derived from a smaller set of image features that we call keypoints. A Gabor filter bank, parameterised empirically by ROC analysis, is used to extract keypoints representing significant scale specific vessel features using an approach inspired by the SIFT algorithm. We first determine keypoints using a validation set and then derive seeds from these points to initialise a k means clustering algorithm which builds a texton dictionary from another training set. During testing we use a simple 1-NN classifier to identify vessel/non-vessel pixels and evaluate our system using the DRIVE database. We achieve average values of sensitivity, specificity and accuracy of 78.12%, 96.68% and 95.05%, respectively. We find that clusters of filter responses from keypoints are more robust than those derived from hand-labelled pixels. This, in turn yields textons more representative of vessel/non-vessel classes and mitigates problems arising due to intra and inter-observer variability. PMID- 26265242 TI - Depression in elderly people living in rural Nigeria and its association with perceived health, poverty, and social network. AB - BACKGROUND: The relationship between late-life depression, poverty, social network, and perceived health is little studied in Africa; the magnitude of the problem remains largely unknown and there is an urgent need to research into this area. METHODS: We interviewed community dwelling elderly persons of two rural areas in Nigeria using Mini-Mental State Examination (MMSE) and Geriatric Depression Scale (GDS-30). Those who scored 11 and above on the GDS-30 were further interviewed using Geriatric Mental State Schedule (GMSS). Diagnosis of depression was based on the International Classification of Diseases 10th edition (ICD-10) and GMSS-Automated Geriatric Examination for Computer Assisted Taxonomy (GMMS-AGECAT). RESULTS: A total of 458 community dwelling elderly persons participated in the study of which 57% were females. Mean age of the participants was 73.65(+/-7.8) years (95% CI 72.93-74.37). The mean GDS-30 and MMSE scores were 4.15(+/-4.80) and 21.73(+/-4.67), respectively. A total of 59 and 58 participants had depression based on ICD-10 criteria and GMSS-AGECAT, respectively. Agreement between ICD-10 and AGECAT diagnoses was kappa = 0.931. By multiple logistic regression analysis, late-life depression was significantly associated with financial difficulties (Odds ratio 4.52 and bereavement Odds ratio 2.70). CONCLUSION: Late-life depression in this cohort is associated with health and socio-economic factors that are worth paying attention to, in a region of economic deprivation and inadequate healthcare. PMID- 26265243 TI - Quadruplex-and-Mg(2+) Connection (QMC) of DNA. AB - This work highlights a novel method of coupling of nucleic acids through formation of an extraordinary stable, specific and fully reversible quadruplex and-Mg(2+) connection (QMC). QMC employs the monomolecular tetrahelical architecture of DNA and has two key components: (i) shape complementarity between QMC partners, which is introduced by specific modifications of the quadruplexes, and (ii) Mg(2+) ions. The on-rate of QMC formation is between 10(5)-10(6) M(-1) s(-1), while the off-rate is undetectable even at 80 degrees C. However, QMC dissociates rapidly upon removal of Mg(2+) ions (i.e., by EDTA). QMC is characterized by high specificity, as even a single-nucleotide modification of one of the connectors inhibits complex-formation. QMC has the potential to revolutionize biotechnology by introducing a new class of capture molecules with major advantages over traditional systems such as streptavidin-biotin. The advantages include reversibility, multiplexing, higher stability and specificity, longer shelf life and low cost. PMID- 26265244 TI - Evaluation of the foetal time to death in mice after application of direct and indirect euthanasia methods. AB - Directive 2010/63/EU on the protection of animals used for scientific purposes requires that the killing of mammal foetuses during the last third of their gestational period should be accomplished through effective and humane methods. The fact that murine foetuses are resistant to hypoxia-mediated euthanasia renders the current euthanasia methods ineffective or humane for the foetuses when these methods are applied to pregnant female mice. We have assessed the time to death of foetuses after performing either indirect (dam euthanasia) or direct (via intraplacental injection--a new approach to euthanasia) euthanasia methods in order to determine a euthanasia method that is appropriate, ethical and efficient for the killing of mouse foetuses. The respective times to death of foetuses after performing the three most commonly used euthanasia methods (namely cervical dislocation, CO2inhalation and intraperitoneal sodium pentobarbital administration) were recorded. Absence of foetal heartbeat was monitored via ultrasound. We consider that the most effective and humane method of foetal euthanasia was the one able to achieve foetal death within the shortest possible period of time. Among the indirect euthanasia methods assessed, the administration of a sodium pentobarbital overdose to pregnant female mice was found to be the fastest for foetuses, with an average post-treatment foetal death of approximately 29.8 min. As for the direct euthanasia method assessed, foetal time to death after intraplacental injection of sodium pentobarbital was approximately 14 min. Significant differences among the different mouse strains employed were found. Based on the results obtained in our study, we consider that the administration of a sodium pentobarbital overdose by intraplacental injection to be an effective euthanasia method for murine foetuses. PMID- 26265245 TI - Electron transfer pathways in mixed-valence paracyclophane-bridged bis triarylamine radical cations. AB - A series of paracyclophane (PC) bridged mixed-valence (MV) bis-triarylamine radical cations with different ([2.2], [3.3], [4.4]) linkers, with and without additional ethynyl spacers, have been studied by quantum-chemical calculations (BLYP35-D3/TZVP/COSMO) of ground-state structures, thermal electron-transfer barriers, hyperfine couplings, and lowest-lying excited states. Such PC-bridged MV systems are important intra-molecular model systems for inter-molecular electron transfer (ET) via pi-stacked aromatics, since they allow enforcement of a more or less well-defined geometrical arrangement. Closely comparable ET barriers and electronic couplings for all [2.2] and [3.3] bridges are found for these class-II MV systems, irrespective of the use of pseudo-para and pseudo-meta connections. While the latter observation contradicts notions of quantum interference for off-resonant conduction through molecular wires, it agrees with the less intricate nodal structures of the highest occupied molecular orbitals. The ET in such MV systems may be more closely connected with hole conduction in the resonant regime. Computations on model cations, in which the [2.2] linkers have been truncated, confirm predominant through-space pi-pi electronic coupling. Systems with [4.4] PC bridges exhibit far more structural flexibility and concomitantly weaker electronic interactions between the redox centers. PMID- 26265246 TI - Factors Associated With the Prevalence of Prostate Cancer in Rural Saskatchewan: The Saskatchewan Rural Health Study. AB - PURPOSE: Prostate cancer is the most commonly diagnosed cancer in Canadian males, and it is the third most common cause of cancer-related deaths in men. Some studies suggest that occupational exposure may be associated with prostate cancer. However, the etiology of prostate cancer is ambiguous. The purpose of this study was to assess the rural occupational exposure, including farming, as a determinant of prostate cancer in rural men. We investigated the prevalence of prostate cancer and its putative relationship between rural exposures in the Saskatchewan province of Canada. METHODS: In 2010, a baseline mailed survey was conducted of 11,982 households located in 4 geographic regions (southwest, southeast, northwest, and northeast) of rural Saskatchewan, Canada. The questionnaires collected information on individual and contextual determinants from a rural population of men. In total 2,938 males older than 45 years were included in the logistic regression analysis. FINDINGS: The age-standardized prevalence of prostate cancer was 3.32%. Farm residence was a significant risk factor associated with prevalence of prostate cancer while farming occupation and duration were not. Men who were exposed to insecticides and fungicides together (OR [95% CI] = 2.23 [1.15-4.33], P = .02) at work showed an increased potential risk compared to the nonexposed. The effect of farm/nonfarm residence on prevalence of prostate cancer differed depending on personal smoking history and family history of cancer. CONCLUSION: Workplace exposure to insecticides and fungicides together were statistically significantly associated with prevalence of prostate cancer. PMID- 26265247 TI - Discovery of new feline paramyxoviruses in domestic cats with chronic kidney disease. AB - Paramyxoviruses constitute a large family of enveloped RNA viruses including important pathogens in veterinary and human medicine. Recently, feline paramyxoviruses, genus morbillivirus, were detected in cats from Hong Kong and Japan. Here we describe the discovery of several new feline paramyxoviruses. Infections with these diverse viruses were detected in urine samples from cats suffering from chronic kidney disease (CKD). No viral RNA was found in cats without clinical signs of uropathy highlighting an association between feline paramyxovirus (FPaV) infections and CKD. Phylogenetic analyses of the detected viruses showed that they represent at least two different species, one of them representing the feline morbilliviruses detected previously in Hong Kong and Japan. In addition, a new FPaV was detected sharing only 73 % homology on the nucleotide level of the viral L-gene to currently known paramyxoviral species. PMID- 26265248 TI - Isolation and sequence analysis of a canine distemper virus from a raccoon dog in Jilin Province, China. AB - Canine distemper virus (CDV) is a major pathogen not only in raccoon dogs but also in a variety of carnivorous animals, including domesticated animals, particularly if they have not been vaccinated. In this study, a wild-type strain of CDV was isolated from lung tissue from a raccoon dog kept at a fur farm in Jilin Province, China. Cytopathic effects typical of CDV infection were observed after three blind passages in Vero cells, yielding a virus titer of 10(4.6) TCID50/mL. Virus identification was carried out by RT-PCR, immunofluorescence, electron microscopy, and genome sequencing. The results showed that the isolated virus, termed the SY strain, corresponded to the Asia-1 genotype of CDV and has a genome of 15,690 nucleotides. This represents the first complete nucleotide sequence of a CDV strain circulating in raccoon dogs in China. PMID- 26265249 TI - Buckling surgery and supplemental intravitreal bevacizumab or photocoagulation on stage 4 retinopathy of prematurity eyes. AB - PURPOSE: To report the results of scleral buckling (SB) with or without photocoagulation (PC) and intravitreal bevacizumab (IVB) for stage 4 retinopathy of prematurity (ROP) eyes. METHODS: Forty-two eyes of 28 patients with SB and/or PC or IVB were studied. Twenty-nine eyes had stage 4A and 13 eyes had stage 4B ROP. Seventeen eyes underwent SB combined with additional intraoperative or postoperative treatments (combined group). Twenty-five eyes underwent SB without additional therapy (non-combined group). The concentrations of vascular endothelial growth factor (VEGF) in the aqueous humor determined by enzyme-linked immunosorbent assay were compared between the two groups. The initial and final reattachment rates were also compared. RESULTS: The gestational age and birth weight were 25.0 +/- 2.0 weeks and 786 +/- 222 g in the combined group, and 25.5 +/- 2.1 weeks and 899 +/- 315 g in the non-combined group. The postmenstrual age at the time of initial surgery was 38.0 +/- 1.9 in the combined and 44.1 +/- 4.0 weeks in the non-combined group (P < 0.001). The initial reattachment rate was 92% in stage 4A and 75% in stage 4B of ROP eyes in the combined group, and the rate was 93% in stage 4A and 33% in stage 4B of ROP eyes in the non-combined group. The mean VEGF concentration in aqueous humor was 1923 +/- 779 pg/ml in the combined group and 985 +/- 303 pg/ml in the non-combined group (P < 0.05). CONCLUSION: Our results show that the retinal reattachment rate after combined therapy was comparable to that in the non-combined group. We conclude that combined therapy may be effective even in ROP eyes with high activity. PMID- 26265250 TI - Oral-tolerization Prevents Immune Responses and Improves Transgene Persistence Following Gene Transfer Mediated by Adeno-associated Viral Vector. AB - Gene therapy represents a feasible strategy to treat inherited monogenic diseases and intramuscular (i.m.) injection of recombinant adeno-associated viral (AAV) vector is now recognized as a convenient and safe method of gene transfer. However, this approach is hampered by immune responses directed against the vector and against the transgenic protein. We used here to reproduce this situation a mouse model where robust immune responses are induced following injection of an AAV vector coding for an immunogenic transgenic protein. We show that prophylactic oral administration of the immunogenic protein before AAV mediated gene transfer completely prevented antibody formation and cytotoxic CD8(+) T-cell response. Consistently, prophylactic oral-tolerization considerably improved long-term transgene persistence and expression. Mechanistically, inhibition of the cytotoxic immune response involved abortive proliferation of antigen-specific cytotoxic CD8(+) T cells, upregulation of the PD-1 immunoregulatory molecule, downregulation of the Bcl-2 antiapoptotic factor, and their deletion in the context of AAV-mediated gene transfer. Hence, gene therapy may represent an ideal situation where oral-tolerization can be adopted before or at the same time as vector injection to efficiently prevent deleterious immune responses directed against the transgenic protein. PMID- 26265251 TI - Directed Alternative Splicing in Nijmegen Breakage Syndrome: Proof of Principle Concerning Its Therapeutical Application. AB - Over 90% of patients with Nijmegen breakage syndrome (NBS), a hereditary cancer disorder, are homoallelic for a 5 bp deletion in the NBN gene involved in the cellular response to DNA damage. This hypomorphic mutation leads to a carboxy terminal protein fragment, p70-nibrin, with some residual function. Average age at malignancy, typically lymphoma, is 9.7 years. NBS patients are hypersensitive to chemotherapeutic and radiotherapeutic treatments, thus prevention of cancer development is of particular importance. Expression of an internally deleted NBN protein, p80-nibrin, has been previously shown to be associated with a milder cellular phenotype and absence of cancer in a 62-year-old NBS patient. Here we show that cells from this patient, unlike other NBS patients, have DNA replication and origin firing rates comparable to control cells. We used here antisense oligonucleotides to enforce alternative splicing in NBS patient cells and efficiently generate the same internally deleted p80-nibrin protein. Injecting the same antisense sequences as morpholino oligomers (VivoMorpholinos) into the tail vein of a humanized NBS murine mouse model also led to efficient alternative splicing in vivo. Thus, proof of principle for the use of antisense oligonucleotides as a potential cancer prophylaxis has been demonstrated. PMID- 26265252 TI - Molecular Modeling Investigation of Folic Acid Conjugation to MDM2 Inhibitors for Enhanced Cellular Uptake and Target Binding. AB - The activation of tumor suppressor p53 protein through inhibition of its interaction with the oncogenic Murine Double Minute 2 (MDM2) protein presents a novel therapeutic strategy against cancer. Accordingly, several small-molecule inhibitors have been developed that mimic three hydrophobic groups of p53 involved in p53-MDM2 binding and thus block the p53-binding pocket on MDM2. Interestingly, presence of a fourth, solvent-exposed hydrophilic moiety in these MDM2 inhibitors is shown to enhance their binding to MDM2 by protecting the inhibitor-MDM2 binding interface from surrounding solvent. In this context, we hypothesized that vitamin folic acid (FA) may prove to be suitable as the hydrophilic cover for enhancing activity of present MDM2 inhibitors. The proposed conjugation of FA to MDM2 inhibitors may also lead to their enhanced and selective uptake by cancer cells, owing to significantly higher expression of the FA receptors on cancer cells compared to normal cells. Therefore, based on our novel hypothesis we designed FA-conjugated MDM2 inhibitors and investigated their binding with MDM2 protein as well as the FA receptor. Specifically, a molecular modeling approach combining flexible receptor docking and molecular mechanics energy minimization calculations revealed highly favorable interactions of FA conjugated MDM2 inhibitors with both MDM2 protein and the FA receptor as compared to native crystal ligands. Furthermore, these binding interactions were found to be stable using 50,000 ps molecular dynamics simulations. In summary, the newly designed molecules of this kind, with better MDM2 target binding and enhanced cellular uptake potential, may prove highly useful against cancer and thus warrant further experimental investigations. PMID- 26265253 TI - Ligand and Structure Based Models for the Identification of Beta 2 Adrenergic Receptor Antagonists. AB - Ligand bound beta 2 adrenergic receptor (beta2AR) crystal structures are in use for screening of compound libraries for identifying inducers and blockers. However, in case of G protein coupled receptors (GPCR), docking and binding energy (BE) calculations are not enough to discriminate agonist and antagonists. Absence of a reliable model for discriminating beta2AR antagonist is still a major hurdle. Docking of known antagonists and agonists into activated and ground state beta2AR revealed several key intermolecular interactions and H-bonding patterns, which in combination, emerged as a model for prediction of antagonists. Present study identifies an alternative binding orientation, within the binding pocket, for blockers and a minimum grid size to lessen the false positive predictions. Cluster analysis revealed structural variability among the antagonists and a conserved pattern in case of agonists. A combination of docking and structure activity relationship (SAR) model reliably discriminated antagonists. Based on key intermolecular interactions, a set of agonists and antagonists useful to SAR, quantitative structure activity relationship (QSAR) and pharmacophore modeling, has also been proposed for identifying antagonists. PMID- 26265255 TI - Molecular phylogeny of Percomorpha resolves Trichonotus as the sister lineage to Gobioidei (Teleostei: Gobiiformes) and confirms the polyphyly of Trachinoidei. AB - The percomorph fish clade Gobiiformes is a worldwide, tropical and temperate radiation with species occupying nearly all aquatic, and some semi-terrestrial, habitats. Early molecular phylogenetic studies led to the discovery of Gobiiformes, which contains Gobioidei, the gobies and sleepers, and a clade (Apogonoidei) consisting of Apogonidae and Kurtus, the cardinalfishes and nurseryfishes. Gobioidei is consistently resolved as monophyletic in molecular studies, and includes eight families whose members range from waterfall climbing stream gobies to several prominent lineages inhabiting coral reefs. The sister taxon to Gobioidei is also reliably resolved as Apogonoidei. Despite the consistent support for gobiiform monophyly in molecular studies, it is not known if percomorph lineages unsampled in molecular phylogenetic studies are closely related to Gobioidei or Apogonoidei. Here we assemble a large dataset of DNA sequence from ten protein-coding genes, sampling widely across Acanthomorpha and Percomorpha, including Gobioidei, Apogonidae, and Kurtus, along with representatives of all twelve families comprising the former Trachinoidei. The phylogenies inferred from the nuclear gene sequences show that Trachinoidei is polyphyletic, with constituent lineages spread widely among several major percomorph clades. Most notably, the sanddivers (Trichonotus) are resolved as the sister lineage of Gobioidei. This study clarifies the phylogenetic relationships of lineages previously classified in Trachinoidei, identifies Trichonotus as the sister lineage of gobies, provides a molecular phylogeny of the major lineages of Gobioidei, and offers suggested changes to percomorph classification. PMID- 26265254 TI - A high-resolution physical map integrating an anchored chromosome with the BAC physical maps of wheat chromosome 6B. AB - BACKGROUND: A complete genome sequence is an essential tool for the genetic improvement of wheat. Because the wheat genome is large, highly repetitive and complex due to its allohexaploid nature, the International Wheat Genome Sequencing Consortium (IWGSC) chose a strategy that involves constructing bacterial artificial chromosome (BAC)-based physical maps of individual chromosomes and performing BAC-by-BAC sequencing. Here, we report the construction of a physical map of chromosome 6B with the goal of revealing the structural features of the third largest chromosome in wheat. RESULTS: We assembled 689 informative BAC contigs (hereafter reffered to as contigs) representing 91% of the entire physical length of wheat chromosome 6B. The contigs were integrated into a radiation hybrid (RH) map of chromosome 6B, with one linkage group consisting of 448 loci with 653 markers. The order and direction of 480 contigs, corresponding to 87% of the total length of 6B, were determined. We also characterized the contigs that contained a part of the nucleolus organizer region or centromere based on their positions on the RH map and the assembled BAC clone sequences. Analysis of the virtual gene order along 6B using the information collected for the integrated map revealed the presence of several chromosomal rearrangements, indicating evolutionary events that occurred on chromosome 6B. CONCLUSIONS: We constructed a reliable physical map of chromosome 6B, enabling us to analyze its genomic structure and evolutionary progression. More importantly, the physical map should provide a high-quality and map-based reference sequence that will serve as a resource for wheat chromosome 6B. PMID- 26265256 TI - Ancient Neotropical origin and recent recolonisation: Phylogeny, biogeography and diversification of the Riodinidae (Lepidoptera: Papilionoidea). AB - We present the first dated higher-level phylogenetic and biogeographic analysis of the butterfly family Riodinidae. This family is distributed worldwide, but more than 90% of the c. 1500 species are found in the Neotropics, while the c. 120 Old World species are concentrated in the Southeast Asian tropics, with minor Afrotropical and Australasian tropical radiations, and few temperate species. Morphologically based higher classification is partly unresolved, with genera incompletely assigned to tribes. Using 3666bp from one mitochondrial and four nuclear markers for each of 23 outgroups and 178 riodinid taxa representing all subfamilies, tribes and subtribes, and 98 out of 145 described genera of riodinids, we estimate that Riodinidae split from Lycaenidae about 96Mya in the mid-Cretaceous and started to diversify about 81Mya. The Riodinidae are monophyletic and originated in the Neotropics, most likely in lowland proto Amazonia. Neither the subfamily Euselasiinae nor the Nemeobiinae are monophyletic as currently constituted. The enigmatic, monotypic Neotropical genera Styx and Corrachia (most recently treated in Euselasiinae: Corrachiini) are highly supported as derived taxa in the Old World Nemeobiinae, with dispersal most likely occurring across the Beringia land bridge during the Oligocene. Styx and Corrachia, together with all other nemeobiines, are the only exclusively Primulaceae-feeding riodinids. The steadily increasing proliferation of the Neotropical Riodininae subfamily contrasts with the decrease in diversification in the Old World, and may provide insights into factors influencing the diversification rate of this relatively ancient clade of Neotropical insects. PMID- 26265257 TI - Comparison of five methods for delimitating species in Ophion Fabricius, a diverse genus of parasitoid wasps (Hymenoptera, Ichneumonidae). AB - DNA taxonomy has been proposed as a method to quickly assess diversity and species limits in highly diverse, understudied taxa. Here we use five methods for species delimitation and two genetic markers (COI and ITS2) to assess species diversity within the parasitoid genus, Ophion. We searched for compensatory base changes (CBC's) in ITS2, and determined that they are too rare to be of practical use in delimiting species in this genus. The other four methods used both COI and ITS2, and included distance-based (threshold analysis and ABGD) and tree-based (GMYC and PTP) models. We compared the results of these analyses to each other under various parameters and tested their performance with respect to 11 Nearctic species/morphospecies and 15 described Palearctic species. We also computed barcode accumulation curves of COI sequences to assess the completeness of sampling. The species count was highly variable depending on the method and parameters used, ranging from 47 to 168 species, with more conservative estimates of 89-121 species. Despite this range, many of the Nearctic test species were fairly robust with respect to method. We concluded that while there was often good congruence between methods, GMYC and PTP were less reliant on arbitrary parameters than the other two methods and more easily applied to genetic markers other than COI. However, PTP was less successful at delimiting test species than was GMYC. All methods, as well as the barcode accumulation curves, indicate that several Palearctic species remain undescribed and that we have scarcely begun to appreciate the Nearctic diversity within this genus. PMID- 26265258 TI - Parametric and non-parametric species delimitation methods result in the recognition of two new Neotropical woody bamboo species. AB - The Neotropical woody bamboo genus Otatea is one of five genera in the subtribe Guaduinae. Of the eight described Otatea species, seven are endemic to Mexico and one is also distributed in Central and South America. Otatea acuminata has the widest geographical distribution of the eight species, and two of its recently collected populations do not match the known species morphologically. Parametric and non-parametric methods were used to delimit the species in Otatea using five chloroplast markers, one nuclear marker, and morphological characters. The parametric coalescent method and the non-parametric analysis supported the recognition of two distinct evolutionary lineages. Molecular clock estimates were used to estimate divergence times in Otatea. The results for divergence time in Otatea estimated the origin of the speciation events from the Late Miocene to Late Pleistocene. The species delimitation analyses (parametric and non parametric) identified that the two populations of O. acuminata from Chiapas and Hidalgo are from two separate evolutionary lineages and these new species have morphological characters that separate them from O. acuminata s.s. The geological activity of the Trans-Mexican Volcanic Belt and the Isthmus of Tehuantepec may have isolated populations and limited the gene flow between Otatea species, driving speciation. Based on the results found here, I describe Otatea rzedowskiorum and Otatea victoriae as two new species, morphologically different from O. acuminata. PMID- 26265259 TI - Morphological and genetic analyses reveal a cryptic species complex in the echinoid Echinocardium cordatum and rule out a stabilizing selection explanation. AB - Preliminary analyses revealed the presence of at least five mitochondrial clades within the widespread sea urchin Echinocardium cordatum (Spatangoida). In this study, we analyzed the genetic (two mitochondrial and two nuclear sequence loci) and morphological characteristics (20 indices) from worldwide samples of this taxon to establish the species limits, morphological diversity and differentiation. Co-occurring spatangoid species were also analyzed with mitochondrial DNA. The nuclear sequences confirm that mitochondrial lineages correspond to true genetic entities and reveal that two clades (named A and B1) hybridize in their sympatry area, although a more closely related pair of clades (B1 and B2), whose distributions widely overlap, does not display hybridization. The morphology of all E. cordatum clade pairs was significantly differentiated, but no morphological diagnostic character was evidenced. By contrast, other spatangoid species pairs that diverged more recently than the E. cordatum clades display clear diagnostic characters. Morphological diversity thus appears responsible for the absence of diagnostic characters, ruling out stabilizing selection, a classical explanation for cryptic species. Alternative classical explanations are (i) environmental plasticity or (ii) a high diversity of genes determining morphology, maintained by varying environmental conditions. We suggest a new hypothesis that the observed morphological diversity is selectively neutral and reflects high effective population sizes in the E. cordatum complex. It is supported by the higher abundance of this taxon compared with other taxa, a trend for the genetic and morphological diversity to be correlated in Europe, and the higher genetic and morphological diversities found in clades of E cordatum (except B1) than in other spatangoid samples in Europe. However, the Pacific clades do not confirm these trends. PMID- 26265261 TI - Asymmetry in genitalia does not increase the rate of their evolution. AB - Left-right asymmetry is a frequently encountered phenomenon in the copulation organs of insects. While various causes have been proposed for genital asymmetry, we raise the question of whether asymmetry might facilitate, or even accelerate, morphological divergence of genitalia between species. We tested this hypothesis in the scarab chafer genus Schizonycha, which comprises species with symmetric as well as asymmetric male genitalia. Morphometric analyses were conducted in the context of their phylogeny, inferred from mitochondrial and nuclear ribosomal DNA sequence data (cox1, rrnL, and 28S) for a sample of 99 South African specimens, including 34 species and 5 outgroup taxa. Trees were reconstructed with maximum likelihood and Bayesian analysis. The extent of asymmetry and the variation of male copulation organs were analyzed with Generalized Procrustes analysis (GPA), by quantifying shape divergence of the parameres. We found a continuous transition in the degree of asymmetry among the investigated species. Ancestral state reconstruction revealed multiple origins and a high degree of evolutionary plasticity of paramere asymmetry in Schizonycha. However, no significant correlation between evolutionary rates of paramere shape divergence and the degree of paramere asymmetry was found, and so we conclude that asymmetric genitalia in Schizonycha do not increase the rate of genital shape divergence. PMID- 26265260 TI - A hairy case: The evolution of filtering carnivorous Drusinae (Limnephilidae, Trichoptera). AB - The caddisfly subfamily Drusinae BANKS comprises roughly 100 species inhabiting mountain ranges in Europe, Asia Minor and the Caucasus. A 3-gene phylogeny of the subfamily previously identified three major clades that were corroborated by larval morphology and feeding ecologies: scraping grazers, omnivorous shredders and filtering carnivores. Larvae of filtering carnivores exhibit unique head capsule complexities, unknown from other caddisfly larvae. Here we assess the species-level relationships within filtering carnivores, hypothesizing that head capsule complexity is derived from simple shapes observed in the other feeding groups. We summarize the current systematics and taxonomy of the group, clarify the systematic position of Cryptothrix nebulicola, and present a larval key to filtering carnivorous Drusinae. We infer relationships of all known filtering carnivorous Drusinae and 34 additional Drusinae species using Bayesian species tree analysis and concatenated Bayesian phylogenetic analysis of 3805bp of sequence data from six gene regions (mtCOI5-P, mtCOI3-P, 16S mrDNA, CADH, WG, 28S nrDNA), morphological cladistics from 308 characters, and a total evidence analysis. All analyses support monophyly of the three feeding ecology groups but fail to fully resolve internal relationships. Within filtering carnivores, variation in head setation and frontoclypeus structure may be associated with progressive niche adaptation, with less complex species recovered at a basal position. We propose that diversification of complex setation and frontoclypeus shape represents a recent evolutionary development, hypothetically enforcing speciation and niche specificity within filtering carnivorous Drusinae. PMID- 26265262 TI - Current status of robotic assisted radical cystectomy with intracorporeal ileal neobladder for bladder cancer. AB - To investigate the current status and feasibility of robotic neobladder diversion after robotic assisted radical cystectomy. A Medline search was conducted resulting in identification of 423 articles. After exclusion of ineligible studies, 3 case series and 5 case reports were considered with a total number of reported cases of 203. Although robotic intracorporeal neobladder reconstruction is in its starting phase, initial perioperative results seem to be comparable to open series. However, randomized studies are needed to confirm non-inferiority. PMID- 26265264 TI - Perinatal outcome after fetoscopic laser surgery for twin-to-twin transfusion syndrome in triplet pregnancies. AB - OBJECTIVES: The introduction of fetoscopic laser surgery of placental anastomoses has led to a significant improvement of perinatal outcome of twin pregnancies affected by twin-to-twin-transfusion syndrome (TTTS). To quantify the perinatal outcome and neurological morbidity in triplet pregnancies complicated by TTTS, which were treated with fetoscopic laser surgery. SEARCH STRATEGY: Medline, Embase, Cinahl and Cochrane were searched. SELECTION CRITERIA: The outcomes observed were: fetal and perinatal survival, preterm birth and abnormal neurological outcome. DATA COLLECTION AND ANALYSIS: Two authors reviewed all abstracts independently. Meta-analyses of proportions were used to combine data. MAIN RESULTS: Eight studies (126 triplet pregnancies, 104 dichorionic-triamniotic [DCTA] and 22 monochorionic-triamniotic [MCTA]) treated with fetoscopic laser surgery were included in this review. In DCTA and MCTA pregnancies, fetal losses were 18.9% and 28.9%, respectively; perinatal losses were 23.6% and 75.0%; preterm births <28 weeks of gestation were 16.9% and 37.1%; preterm births <32 weeks of gestation were 50.0% and 69.5%; at least one fetus survived in 95.4% and 88.9% of the pregnancies; at least two fetuses survived in 81.8% and 68.3% of the pregnancies; and in 55.9% and 48.4% pregnancies all triplets survived. Finally, the incidence of abnormal neurological outcomes ranged from 0 to 37% in DCTA and from 0 to 50% in MCTA triplets. CONCLUSIONS: Both DTCA and MCTA triplet pregnancies affected by TTTS are at high risk of adverse perinatal outcome. TWEETABLE ABSTRACT: Both DTCA and MCTA triplet pregnancies affected by TTTS are at high risk of adverse perinatal outcome. PMID- 26265265 TI - Hidradenoma papilliferum associated with pregnancy: a case report. AB - We present the case of a 33-year-old female who developed a cystic nodule on the vulva during pregnancy. Immediately following Cesarean section, the lesion was biopsied and histologic examination revealed a dermal tumor composed of glandular structures arranged in a labyrinth pattern. The glandular structures displayed cytoplasmic vacuolization, large atypical nuclei, prominent nucleoli and scattered eosinophilic luminal secretions. Immunohistochemistry showed the tumor cells to be diffusely positive for CK7 and progesterone receptor with focal expression of mammaglobin and GCDFP-15. The tumor cells were negative for estrogen receptor and CK20. These histologic and immunophenotypic findings were consistent with hidradenoma papilliferum. Our unusual (and to our knowledge first reported) case demonstrates hidradenoma papilliferum in association with pregnancy and raises the possibility of cytologic atypia and lactational change being secondary to hormonal changes in pregnancy. PMID- 26265266 TI - Multiple Sclerosis is a multifaceted disease. PMID- 26265263 TI - Association between anti-Porphyromonas gingivalis or anti-alpha-enolase antibody and severity of periodontitis or rheumatoid arthritis (RA) disease activity in RA. AB - BACKGROUND: Periodontitis (PD) has been reported to be associated with rheumatoid arthritis (RA). Porphyromonas gingivalis (P. gingivalis) is a gram-negative anaerobic bacterium that is recognized as one of the major pathogenic organisms in PD and is the only bacterium known to express peptidylarginine deiminase (PAD). Antibody against human alpha-enolase (ENO1) is one of the autoantibodies in RA. ENO1 is a highly conserved protein, and could be a candidate molecule for molecular mimicry between bacterial and human proteins. In the present study, we measured serum antibody against P. gingivalis and human ENO1 in patients with RA and investigated their association with the severity of PD or disease activity of RA. METHODS: Two hundred, forty-eight patients with RA and 85 age- and sex matched healthy controls were evaluated by rheumatologic and periodontal examinations. The serum levels of anti-P. gingivalis and anti-ENO1 antibodies were measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Patients with RA had significantly higher levels of anti-P. gingivalis and anti-ENO1 antibody titers than the controls (p = 0.002 and 0.0001, respectively). Anti-P. gingivalis antibody titers significantly correlated with anti-ENO1 antibody titers in RA patients (r = 0.30, p < 0.0001). There were significant correlations between anti-P. gingivalis antibody titers and the gingival index (GI), probing pocket depth (PPD), bleeding on probing (BOP) and clinical attachment level (CAL) (p = 0.038, 0.004, 0.004 and 0.002, respectively) in RA. Anti-P. gingivalis antibody titers were not correlated with disease activity score 28 (DAS28) or anti-CCP titer. However, anti-ENO1 antibody titers were significantly correlated not only with the periodontal indices, such as PPD, BOP, and CAL (p = 0.013, 0.023 and 0.017, respectively), but also RA clinical characteristics, such as DAS28, anti-CCP titer, and ESR (p = 0.009, 0.015 and 0.001, respectively). CONCLUSION: Anti-P. gingivalis and anti-ENO1 antibody titers were correlated with the severity of PD in RA. Anti-ENO1 antibody titers, but not anti-P. gingivalis antibody titers, were further associated with RA disease activity. PMID- 26265267 TI - Experimental autoimmune encephalomyelitis is a good model of multiple sclerosis if used wisely. AB - Although multiple sclerosis is a uniquely human disease, many pathological features can be induced in experimental autoimmune encephalomyelitis (EAE) models following induction of central nervous system-directed autoimmunity. Whilst it is an imperfect set of models, EAE can be used to identify pathogenic mechanisms and therapeutics. However, the failure to translate many treatments from EAE into human benefit has led some to question the validity of the EAE model. Whilst differences in biology between humans and other species may account for this, it is suggested here that the failure to translate may be considerably influenced by human activity. Basic science contributes to failings in aspects of experimental design and over-interpretation of results and lack of transparency and reproducibility of the studies. Importantly issues in trial design by neurologists and other actions of the pharmaceutical industry destine therapeutics to failure and terminate basic science projects. However animal, particularly mechanism-orientated, studies have increasingly identified useful treatments and provided mechanistic ideas on which most hypothesis-led clinical research is based. Without EAE and other animal studies, clinical investigations will continue to be "look-see" exercises, which will most likely provide more misses than hits and will fail the people with MS that they aim to serve. PMID- 26265268 TI - EAE is not a useful model for demyelinating disease. AB - Experimental allergic encephalomyelitis (EAE) is the commonest, readily induced, organspecific, autoimmune disorder of laboratory animals of its kind. It is an artificial disorder brought about by the immunisation of susceptible animals with brain antigens in complete Freund's adjuvant (CFA). Variations can be induced by altering the nature of the antigen and the conditions involving immunisation. Whilst it is often described as a demyelinating disease, in strict terms it is not, since the primary pathologic process is not demyelination but rather an encephalomyelitis that is immunologically induced. Rather, the prototype demyelinating disease is multiple sclerosis and its variants. In this paper, the central question we ask is whether the data gleaned from the EAE model contributes to our understanding of the pathological events in MS. Towards answering this, we describe the historical development of EAE and its hyperacute form, and discuss the findings studied extensively in the non-human primate which show that ordinary EAE is an exact model for ADEM in the human, and that the hyperacute form of EAE is represented by AHLE in the human. Additionally, we shall comment on the latest research on new variants of EAE, and explain our opinion regarding the use of EAE models in research aiming to understand the pathogenesis of multiple sclerosis. PMID- 26265269 TI - A web-based decision support tool for prognosis simulation in multiple sclerosis. AB - A multiplicity of natural history studies of multiple sclerosis provides valuable knowledge of the disease progression but individualized prognosis remains elusive. A few decision support tools that assist the clinician in such task have emerged but have not received proper attention from clinicians and patients. The objective of the current work is to implement a web-based tool, conveying decision relevant prognostic scientific evidence, which will help clinicians discuss prognosis with individual patients. Data were extracted from a set of reference studies, especially those dealing with the natural history of multiple sclerosis. The web-based decision support tool for individualized prognosis simulation was implemented with NetLogo, a program environment suited for the development of complex adaptive systems. Its prototype has been launched online; it enables clinicians to predict both the likelihood of CIS to CDMS conversion, and the long-term prognosis of disability level and SPMS conversion, as well as assess and monitor the effects of treatment. More robust decision support tools, which convey scientific evidence and satisfy the needs of clinical practice by helping clinicians discuss prognosis expectations with individual patients, are required. The web-based simulation model herein introduced proposes to be a step forward toward this purpose. PMID- 26265270 TI - Continuous prediction of secondary progression in the individual course of multiple sclerosis. AB - BACKGROUND: Prediction of the course of multiple sclerosis (MS) was traditionally based on features close to onset. OBJECTIVE: To evaluate predictors of the individual risk of secondary progression (SP) identified at any time during relapsing-remitting MS. METHODS: We analysed a database comprising an untreated MS incidence cohort (n=306) with five decades of follow-up. Data regarding predictors of all attacks (n=749) and demographics from patients (n=157) with at least one distinct second attack were included as covariates in a Poisson regression analysis with SP as outcome. RESULTS: The average hazard function of transition to SPMS was 0.046 events per patient year, showing a maximum at age 33. Three covariates were significant predictors: age, a descriptor of the most recent relapse, and the interaction between the descriptor and time since the relapse. A hazard function termed "prediction score" estimated the risk of SP as number of transition events per patient year (range <0.01 to >0.15). CONCLUSIONS: The insights gained from this study are that the risk of transition to SP varies over time in individual patients, that the risk of SP is linked to previous relapses, that predictors in the later stages of the course are more effective than the traditional onset predictors, and that the number of potential predictors can be reduced to a few (three in this study) essential items. This advanced simplification facilitates adaption of the "prediction score" to other (more recent, benign or treated) materials, and allows for compact web-based applications (http://msprediction.com). PMID- 26265271 TI - Associations between onset age and disability in multiple sclerosis patients studied using MSSS and a progression model. AB - BACKGROUND: While many factors have been examined, male gender and older age at multiple sclerosis onset are among few variables consistently associated with increased disability. Interestingly, the association between onset age and disability may not be linear with some data suggesting a faster rate of accumulation of disability in patients aged more than 30 years at onset. OBJECTIVE: Explore the relationship between onset age and disability. METHODS: We studied 500 MS patients grouped by cut-offs in onset age. Disability was assessed using Multiple Sclerosis Severity Scale (MSSS) and, a model based on time to reach an Extended Disability Severity Score (EDSS) (progression model). Data were analyzed using linear and logistic regression. RESULTS: The association between disability (assessed by both MSSS and the progression model) and onset age was different in patients whose MS onset occurred after an age band of 30-35 years. Before this age range, changing age was not associated with changes in disability while during and after this age range, disability was increased. CONCLUSION: We found a significant change in the relationship between disability and onset age after about 31 years supporting the idea that while onset age does not define a sharp cut-off, it can help define subgroups of patients with differing rates of accumulation of disability. PMID- 26265272 TI - Physical and social environment and the risk of multiple sclerosis. AB - BACKGROUND: The incidence of multiple sclerosis (MS) in Denmark has doubled in women since 1970, whereas it has been almost unchanged in men. The rapid epidemiological changes suggest that environmental factors may modify the risk of MS. OBJECTIVES: To investigate whether occupational, physical, or social environmental influence the risk of MS differently in women than in men. METHODS: The cohort consists of all 1403 patients (939 women, 464 men) identified through Danish Multiple Sclerosis Registry aged 1-55 of years at clinical onset between 2000 and 2004, and up to 25 control persons for each case, matched by sex, year of birth and residential municipality. The same cohort was previously used to investigate the influence of the reproductive factors on the risk of MS. RESULTS: By linkage to Danish population registers we found a slight albeit statistically significant excess for 6 female MS patients who had been employed in agriculture: OR 3.52; 95% CI 1.38-9.00, p=0.008 (0.046 when corrected for multiple significance) and a trend for exposure to outdoor work in 12 : OR 1.94, 95% CI 1.06-3.55, p=0.03 (0.09 when corrected for multiple significance), but the numbers of cases were small, and the effects were not found in men. Educational level, housing conditions in youth, or the presence of children unrelated by blood in the household did not influence the risk of MS. CONCLUSIONS: Our study did not reveal any additional factors beyond the previously published childbirths which could explain the extent of the MS incidence increase in women. PMID- 26265273 TI - Outcomes of switching directly to oral fingolimod from injectable therapies: Results of the randomized, open-label, multicenter, Evaluate Patient OutComes (EPOC) study in relapsing multiple sclerosis. AB - BACKGROUND: The Evaluate Patient OutComes (ClinicalTrials.gov Identifier: NCT01216072) study was conducted in North America to assess patient- and physician-reported treatment satisfaction in patients with relapsing multiple sclerosis (MS) who received oral fingolimod for 6 months after switching from an injectable disease-modifying therapy (iDMT), without an intervening washout. METHODS: In this open-label, multicenter study, patients were randomized 3:1 to once-daily fingolimod 0.5mg or iDMT. The primary study objective was to evaluate differences in satisfaction measured using the Treatment Satisfaction Questionnaire for Medication v1.4. RESULTS: Of 1053 patients randomized, 790 patients received fingolimod and 263 patients received iDMT. Treatment satisfaction improved significantly in patients who switched to fingolimod compared with those who continued iDMT. Patients also reported significant improvements in health-related quality of life, reduced depression, and reduced fatigue severity after a switch to fingolimod. No difference between the treatment groups was detected on the Patient Reported Indices for MS Activities scale. The safety profile of fingolimod was consistent with that reported in the pivotal phase 3 studies. The most commonly reported adverse events were more prevalent in patients who switched to fingolimod than in those who continued iDMT (headache: 12% vs 3%; fatigue: 12% vs 6%). No significant relationship between lymphocyte counts and infection rates was observed and there was no evidence of additive immune-system effects, which might be expected when switching to a different class of immunomodulatory therapy with no intervening washout. CONCLUSION: Patients who switched from iDMT to fingolimod had significant improvements in most self-reported outcomes compared with those who continued iDMT. PMID- 26265274 TI - First-dose effects of fingolimod after switching from injectable therapies in the randomized, open-label, multicenter, Evaluate Patient OutComes (EPOC) study in relapsing multiple sclerosis. AB - BACKGROUND: In pivotal phase 3 studies, fingolimod treatment initiation was associated with a transient reduction in heart rate (HR). Atrioventricular (AV) conduction delays, which were typically asymptomatic, were detected in a small minority of patients. OBJECTIVE: We report the first-dose effects of fingolimod in patients who switched from injectable therapies during the Evaluate Patient OutComes (EPOC) study (ClinicalTrials.gov Identifier: NCT01216072). METHODS: This was a phase 4, 6-month, randomized, active-comparator, open-label, multicenter study. It included over 900 fingolimod-treated patients with relapsing multiple sclerosis, with subgroups of individuals who were receiving common concomitant HR lowering medications or had pre-existing cardiac conditions (PCCs). Vital signs were recorded hourly for 6h post-dose. A 12-lead electrocardiogram was obtained at baseline and at 6h post-dose. RESULTS: A transient decrease in mean HR and blood pressure occurred within 6h of the first fingolimod dose. The incidence of symptomatic bradycardia was low (1%); eight patients reported dizziness and there was one case each of fatigue, palpitations, dyspnea, cardiac discomfort, and gait disturbance. These symptomatic events were typically mild or moderate in severity and all resolved spontaneously, without intervention or fingolimod discontinuation. CONCLUSION: First-dose effects in patients with PCCs and in those receiving concomitant HR-lowering medications were consistent with effects observed in the overall study population and with results from previous clinical trials. The EPOC study provides additional data demonstrating the transient and generally benign nature of fingolimod first-dose effects on HR and AV conduction in a large population that is more representative of patients encountered in routine clinical practice than in the pivotal trials. PMID- 26265275 TI - First-dose effects of fingolimod: Pooled safety data from three phase 3 studies. AB - Fingolimod treatment initiation is associated with a transient slowing of heart rate and atrioventricular conduction. This report presents first-dose fingolimod effects (0.5mg or 1.25mg) on cardiac parameters using phase 3 FREEDOMS, FREEDOMS II and TRANSFORMS pooled study data (n=3635 patients). Vital signs were recorded hourly for >=6h; 12-lead electrocardiogram (ECG) was obtained at baseline and at 6h post-dose. Clinical events were graded at the first-dose administrator's discretion. At screening, on day 1 and at month 3, 1073 patients underwent 24-h ambulatory electrocardiogram monitoring. A transient decrease in mean measured heart rate occurred 4-5h after the first dose, with a maximum reduction of 8 (fingolimod 0.5mg) and 11 beats per minute (fingolimod 1.25mg) below baseline. Symptomatic bradycardia at treatment initiation was reported in 0.6% (fingolimod 0.5mg) and 2.1% (fingolimod 1.25mg) of patients; events were typically mild or moderate in severity, and most resolved spontaneously. Atrioventricular (AV) conduction delays were observed in a few patients (Wenckebach (Mobitz type I) second-degree AV block, fingolimod 0.5mg, 0.2%; 1.25mg, 1%: 2:1 AV block fingolimod, 0.5mg, 0%; 1.25mg, 0.2% on ECG 6-h post-dose). These were usually well tolerated and first occurred within 6h of dosing. Consistent with its effects on atrial myocytes, fingolimod treatment initiation induced a transient slowing of heart rate and AV conduction. However, symptomatic bradycardia and second-degree AV block were uncommon and did not require intervention. PMID- 26265276 TI - CD20+inflammatory T-cells are present in blood and brain of multiple sclerosis patients and can be selectively targeted for apoptotic elimination. AB - BACKGROUND: A subset of T-cells expresses the B-cell marker CD20 and in rheumatoid arthritis secretes Interleukin (IL)-17. IL-17 secreting T-cells (Th17) have also been implicated in the inflammatory response in the central nervous system in multiple sclerosis (MS) and may be a potential target for elimination by biologic therapeutics. ScFvRit:sFasL comprises of a rituximab-derived antibody fragment scFvRit genetically fused to human soluble FasL that specifically eliminated T-cells. OBJECTIVE: To determine the presence and phenotype of CD20+T cells in blood and brain of MS patients. Second, to determine whether scFvRit:sFasL can selectively eliminate CD20+T-cells. After CD20-selective binding, scFvRit:sFasL is designed to trigger FasL-mediated activation-induced cell death of T-cells, but not B-cells. METHODS: Flow cytometry and immunohistochemistry were used to screen for CD20+inflammatory T-cells in MS blood and brain tissue. ScFvRit:sFasL pro-apoptotic activity was evaluated by Annexin-V/PI staining followed by flow cytometry assessment. RESULTS: Peripheral blood (n=11) and chronic but not active lesions of MS patient brains (n=5) contained CD20+inflammatory T-cells. Activated CD20+T-cells were predominantly CD4+and secreted both IL-17 and INF-gamma. ScFvRit:sFasL triggered CD20 restricted FasL-mediated activation-induced cell death in peripheral blood CD20+T cells, but not CD20+B-cells. CONCLUSION: CD20+inflammatory T-cells are present in blood and chronic brain lesions of MS patients. ScFvRit:sFasL selectively eliminated CD20+T-cells and may eliminate pathogenic T-cells without B-cell depletion. PMID- 26265277 TI - Immune reconstitution inflammatory syndrome and natalizumab-Is it possible before removing the drug? AB - Multiple sclerosis (MS) patients treated with natalizumab have a significant reduction in annualized relapse rate; in these patients, a relapse is uncommon but not unexpected. In contrast, the appearance of a severe exacerbation is striking and requires the differential diagnosis with progressive multifocal leukoencephalopathy. Here, we describe a case of a 22-year-old woman with relapsing-remitting MS who developed an unexpected response after the patient's fifth natalizumab infusion with an aggressive radiological and clinical evolution. Changing the patient's treatment to fingolimod resulted in the absence of new clinical relapses and the absence of active lesions on brain magnetic resonance images (MRI) during the first 12 months of follow-up. We hypothesize that the appearance of natalizumab antibodies in this patient triggered lymphocyte migration to the central nervous system in a rebound phenomenon; this is similar to what occurs during immune reconstitution inflammatory syndrome (IRIS) after removal of natalizumab. PMID- 26265278 TI - P wave duration and dispersion and QT interval in multiple sclerosis. AB - INTRODUCTION: Multiple sclerosis (MS) is one of the most frequent disorders of central nervous system, resulting in autonomic disturbances. Some electrocardiographic changes have been reported in these patients that can lead to arrhythmia. In this study we compared P wave duration and dispersion and QT interval of MS patients to healthy control subjects. MATERIAL AND METHODS: Eighty four multiple sclerosis patients and 84 healthy, age and sex-matched volunteers were included. A 12-lead electrocardiogram was undertaken in order to measure minimal and maximal P wave duration, P wave dispersion (PWD) and QT interval. RESULTS: In patient group, mean P wave duration, maximum P wave duration and PWD were significantly longer than control group. QT interval was longer in patient group but the difference was not significant. CONCLUSION: In this study, P wave duration and P wave dispersion was found to be higher in MS patients than healthy control subjects. PMID- 26265280 TI - Safety analysis of the oncological outcome after vein-preserving surgery for colorectal liver metastases detached from the main hepatic veins. AB - PURPOSE: Recent studies have reported that margins alone do not predict survival in patients with a positive chemotherapy response. The aim of this retrospective study is to analyze the surgical and oncological outcomes of patients who underwent chemotherapy and liver resection for colorectal liver metastases (CRLM) with lesions detached from the main hepatic veins, comparing the vein-preserving (VP) approach with traditional surgery. METHODS: Fourteen patients undergoing VP surgery from January 2006 to January 2013 were matched in a 1:2 ratio with a control group (CG) of 28 patients undergoing traditional resection. RESULTS: The median follow-up was 43 months. The radiological response was classified as 'partial response' in eight VP patients and 11 controls (57 vs. 39 %, p = 0.249) and as 'stable disease' in three VP patients and 9 controls (21 vs. 32 %, p = 0.465). Ten VP (71.4 %) and twenty CG patients (71.4 %) experienced tumor relapse (p = 0.99). No venous edge recurrences were recorded in the VP group, whereas 1/13 (7.7 %) was observed in the control group (p = 0.99). The pathological response rate was 64 vs. 39 % (p = 0.037) in VP and CG patients, respectively. The 5-year recurrence-free survival rate was 24 % for VP patients and 25 % for CG patients (p = 0.431). CONCLUSION: In patients with a positive CT response, CRLM can be detached from the hepatic veins, as the oncological outcome is similar to that of a larger resection. The VP approach offers the possibility to enlarge the surgical indications, thus optimizing future surgical treatment chances. PMID- 26265279 TI - Comparison of the effectiveness of low pressure pneumoperitoneum with profound muscle relaxation during laparoscopic donor nephrectomy to optimize the quality of recovery during the early post-operative phase: study protocol for a randomized controlled clinical trial. AB - BACKGROUND: Since technique modifications of laparoscopic donor nephrectomy, e.g. retroperitoneoscopic donor nephrectomy or hand-assistance, have not shown significant benefit regarding safety or improvement of recovery, further research should focus on improving postoperative recovery. The use of low pressure pneumoperitoneum has shown to significantly reduce postoperative pain after laparoscopy. To facilitate the use of low pressure pneumoperitoneum, deep neuromuscular block will be used. METHODS/DESIGN: This trial is a phase IV, single center, double-blind, randomized controlled clinical trial in which 64 patients will be randomized to: low pressure pneumoperitoneum (6 mmHg) and deep neuromuscular block or normal pressure pneumoperitoneum (12 mmHg) and deep neuromuscular block. Deep neuromuscular block is defined as post tetanic count < 5. Primary outcome measurement will be Quality of Recovery-40 questionnaire (overall score) on day 1. DISCUSSION: This study is the first randomized study to assess the combination of low pressure pneumoperitoneum in combination with deep neuromuscular block from a patients' perspective. The study findings may also be applicable for other laparoscopic procedures. TRIAL REGISTRATION: The trial was registered at trials.gov (NCT02146417) in July 2014. PMID- 26265283 TI - Virginity dilemma: Re-creating virginity through hymenoplasty in Iran. AB - Bridal virginity retains undeniable value in Iran's contemporary cultural landscape. Widely regarded as a sign of chastity and purity for unmarried girls, failure to prove virginity on the wedding night may have serious consequences for a girl. In this context, there has been a recent growth in the rate of hymen restoration surgery (hymenoplasty) due to an increase in the number of girls who engage in premarital sexual relationships. The present study attempts to elucidate the processes through which particular physical features come to be considered culturally meaningful, and explores the phenomenon of hymen reconstructing surgery from the perspective of young Tehrani girls and boys. Applying anthropological insights into gender roles, I explore how so-called 'rebellious' Iranian girls find - through the surgical reconstruction of their hymen - a means to negotiate between dominant models of gender and their own subjective experiences. While their actions challenge the premarital sex taboo, Iranian girls who participate in hymen restoration surgery also conform to the values that require them to be a virgin at the time of marriage, thus reinforcing existing power relations. PMID- 26265281 TI - Chiari I Malformation in Nephropathic Cystinosis. AB - OBJECTIVE: To determine the relative incidence of Chiari I malformations in children with cystinosis compared with those in the general population. STUDY DESIGN: Magnetic resonance imaging scans were performed on 53 patients with nephropathic cystinosis and 120 controls, age range 3-18 years. RESULTS: Ten of 53 (18.9%) patients with cystinosis had Chiari I or tonsillar ectopia, and only 2 of 120 controls (1.6%) had a similar finding. At least 2 of the patients had symptoms or signs thought to be related to the malformation, and one had surgical decompression. Two had an associated cervical syrinx. CONCLUSIONS: Children with cystinosis have a 12-fold higher prevalence of Chiari I malformations than the general pediatric population. Chiari I malformations should be high on the differential diagnosis when individuals with cystinosis develop neurologic signs and symptoms, and magnetic resonance imaging scans should be performed on children with cystinosis who present with new-onset headache, ataxia, incontinence, or other unexplained neurologic symptoms. PMID- 26265284 TI - Long non-coding RNA HOTTIP promotes tumor growth and inhibits cell apoptosis in lung cancer. AB - Lung cancer is one of the leading causes of cancer-related deaths worldwide. Early diagnosis is the best defense against this threat and is therefore of vital importance. In this study, we investigated the role of long non-coding RNA HOTTIP in the tumor growth of lung cancer. Initially, we found that expression of HOTTIP was significantly elevated in 20 cases of lung cancer. HOTTIP was also differentially expressed in a consecutive of lung cancer cell lines. Furthermore, specific shRNA against HOTTIP was employed to deplete expression of HOTTIP in A549 cells and NCI-H446 cells. After successfully depletion of HOTTIP, cell proliferation and colony formation were significantly inhibited in vitro. Tumor growth in vivo was also suppressed after depletion of HOTTIP in a mouse model of lung cancer. Moreover, depletion of HOTTIP caused cell cycle arrest in G0/G1 phase and induced significant cell apoptosis. Cell cycle regulators Cdc25C, Cyclin B1 and Cyclin D1 were decreased upon depletion of HOTTIP. Pro-apoptotic factor Bad was up-regulated, whereas anti-apoptotic factors Bcl-2 and Bcl-xL were down-regulated after HOTTIP ablation. These data suggest that lncRNA HOTTIP contributes to tumor growth in vivo and in vitro and inhibits cell apoptosis in lung cancer. PMID- 26265285 TI - A Fatality Related to Two Novel Hallucinogenic Compounds: 4-Methoxyphencyclidine and 4-Hydroxy-N-methyl-N-ethyltryptamine. AB - In this case report, we present an evaluation of postmortem concentration distribution of the hallucinogenic compound 4-methoxyphencyclidine (4-MeO-PCP) in a fatality principally attributed to this drug. Another hallucinogen, 4-hydroxy-N methyl-N-ethyltryptamine was also detected, but was not quantitated. A man--who had a history of recent 'strange' behavior--was found deceased, on his bed, in his locked room. Toxicology testing, which initially screened positive for phencyclidine (PCP) by ELISA, subsequently detected and confirmed the two hallucinogens by gas chromatography-mass spectrometry. 4-MeO-PCP concentrations were then quantified by a specific secondary testing technique. The peripheral blood concentration was 8.2 mg/L compared with the central blood concentration of 14 mg/L. The liver concentration was 120 mg/kg, the vitreous was 5.1 mg/L, the urine was 140 mg/L and the gastric contents contained 280 mg. PCP was not detected, but therapeutic concentrations of venlafaxine, olanzapine, lorazepam and hydroxyzine were confirmed. The cause of death was certified due to acute mixed drug intoxication, and the manner of death was certified as accident. PMID- 26265282 TI - Effects of Advancing Gestation and Non-Caucasian Race on Ductus Arteriosus Gene Expression. AB - OBJECTIVE: To identify genes affected by advancing gestation and racial/ethnic origin in human ductus arteriosus (DA). STUDY DESIGN: We collected 3 sets of DA tissue (n = 93, n = 89, n = 91; total = 273 fetuses) from second trimester pregnancies. We examined four genes, with DNA polymorphisms that distribute along racial lines, to identify "Caucasian" and "non-Caucasian" DA. We used real time polymerase chain reaction to measure RNA expression of 48 candidate genes involved in functional closure of the DA, and used multivariable regression analyses to examine the relationships between advancing gestation, "non Caucasian" race, and gene expression. RESULTS: Mature gestation and non-Caucasian race are significant predictors for identifying infants who will close their patent DA when treated with indomethacin. Advancing gestation consistently altered gene expression in pathways involved with oxygen-induced constriction (eg, calcium-channels, potassium-channels, and endothelin signaling), contractile protein maturation, tissue remodeling, and prostaglandin and nitric oxide signaling in all 3 tissue sets. None of the pathways involved with oxygen-induced constriction appeared to be altered in "non-Caucasian" DA. Two genes, SLCO2A1 and NOS3, (involved with prostaglandin reuptake/metabolism and nitric oxide production, respectively) were consistently decreased in "non-Caucasian" DA. CONCLUSIONS: Prostaglandins and nitric oxide are the most important vasodilators opposing DA closure. Indomethacin inhibits prostaglandin production, but not nitric oxide production. Because decreased SLCO2A1 and NOS3 expression can lead to increased prostaglandin and decreased nitric oxide concentrations, we speculate that prostaglandin-mediated vasodilation may play a more dominant role in maintaining the "non-Caucasian" patent DA, making it more likely to close when inhibited by indomethacin. PMID- 26265286 TI - Metallic Profile of Whole Blood and Plasma in a Series of 99 Healthy Children. AB - In recent years, special emphasis has been put on heavy metals. Children are very sensitive to accumulation of metals. Furthermore, as regards elements, the reference values in children are scarce in the literature as it is difficult to obtain the large quantity of blood necessary to analyze many metals by the conventional atomic absorption spectrometry technique. An inductively coupled plasma mass spectrometry (ICP-MS) procedure that uses a reduced sample of 0.3 mL whole blood or plasma is adapted to multielemental determinations. We applied a previously validated technique for adults that simultaneously quantifies 25 elements by ICP-MS in whole blood and 23 in plasma in a series of 99 healthy children ranging from under 5 years to <18 years, without exposure to metal or drug-containing metals. The aims of the study were to compare metallic concentrations according to the age among children and metallic concentration differences between children and adults. The blood and plasma pediatric metallic profile is a practical useful tool for many purposes in clinical toxicology, forensic toxicology and any cases of metal environmental exposure. PMID- 26265287 TI - Classification of unexpected infant deaths: what can we learn from international comparisons? PMID- 26265288 TI - Parental attitudes to clinical studies in healthy siblings. PMID- 26265289 TI - Altered topological properties in the heritable schizophrenic brain. PMID- 26265290 TI - Adjuvant radiotherapy in the treatment of gall bladder carcinoma: What is the current evidence. AB - Gall bladder carcinoma (GBC) is considered the fifth most common one of the most aggressive gastro intestinal tract malignancies. Owing to their large incidence randomised controlled trials have hardly been conducted to look into their optimum treatment. Over the years surgical resection has been considered the only curative treatment of these tumors. However, the outcome still remains guarded. The predominant pattern of failure is loco-regional followed by systemic. Hence, local adjuvant radiation has been used by different institutes with concurrent and adjuvant chemotherapy. The large retrospective series with their limitations showed improved survival in patients with regional spread or tumors infiltrating the liver when treated with adjuvant radiotherapy. In the present era with modern radiation techniques and target delineation radiation may further improve upon the impact without adding to the toxicity profile. Hence, radiation in gall bladder cancer needs a relook to optimize treatment outcome of such aggressive disease. PMID- 26265292 TI - Hyperpolarized (6)Li as a probe for hemoglobin oxygenation level. AB - Hyperpolarization by dissolution dynamic nuclear polarization (DNP) is a versatile technique to dramatically enhance the nuclear magnetic resonance (NMR) signal intensity of insensitive long-T1 nuclear spins such as (6)Li. The (6)Li longitudinal relaxation of lithium ions in aqueous solutions strongly depends on the concentration of paramagnetic species, even if they are present in minute amounts. We herein demonstrate that blood oxygenation can be readily detected by taking advantage of the (6)Li signal enhancement provided by dissolution DNP, together with the more than 10% decrease in (6)Li longitudinal relaxation as a consequence of the presence of paramagnetic deoxyhemoglobin. PMID- 26265293 TI - Dietary intake of iron, zinc, copper, and risk of Parkinson's disease: a meta analysis. AB - Although some studies have reported the associations between specific metal element intake and risk of Parkinson's disease (PD), the associations between specific metal element intake such as iron intake and PD are still conflicted. We aimed to determine whether intake of iron, zinc, and copper increases/decreases the risk of PD. PubMed, Embase, Web of Knowledge, and Google Scholar were searched. We pooled the multivariate-adjusted relative risks (RRs) or odds ratios using random effects. Study quality was evaluated by the Newcastle-Ottawa Scale. Five studies including 126,507 individuals remained for inclusion, pooled RRs of Parkinson's disease for moderate dietary iron intake was 1.08 (95 % CI 0.61-1.93, P = 0.787), and for high dietary iron intake was (1.03, 95 % CI 0.83-1.30, P = 0.766), respectively. The pooled RRs of Parkinson's disease for the highest compared with the lowest dietary iron intake were 1.47 (95 % CI 1.17-1.85, P = 0.001) in western population and in males (RR = 1.43, 95 % CI 1.01-2.01, P = 0.041). The pooled RRs of Parkinson's disease for moderate or high intake of zinc, and copper were not statistically different (P > 0.05). PD increased by 18 % (RR 1.18, 95 % CI 1.02-1.37) for western population by every 10-mg/day increment in iron intake. Higher iron intake appears to be not associated with overall PD risk, but may be associated with risk of PD in western population. Sex may be a factor influencing PD risk for higher iron intake. However, further studies are still needed to confirm the sex-selective effects. PMID- 26265294 TI - Pediatric paroxysmal hemicrania: a case report and some clinical considerations. PMID- 26265295 TI - Short-term high-fat diet increases postprandial trimethylamine-N-oxide in humans. AB - The gut microbiota plays an obligatory role in the metabolism of nutrients containing trimethylamine moieties, such as L-carnitine and choline, leading to the production of the proatherogenic trimethylamine-N-oxide (TMAO). We hypothesized that a short-term, high-fat diet would increase fasting and postprandial plasma concentrations of TMAO in response to a high-fat meal challenge. Following a 2-week eucaloric control diet, 10 nonobese men (18-30 years) consumed a eucaloric, high-fat diet (55% fat) for 5 days. Plasma TMAO was measured after a 12-hour fast and each hour after for 4 hours following a high fat meal (63% fat) at baseline and after the high-fat diet using ultraperformance liquid chromatography/ tandem mass spectrometry. Fasting plasma TMAO did not increase significantly following the high-fat diet (1.83 +/- 0.21 vs 1.6 +/- 0.24 MUmol/L). However, plasma TMAO was higher at hour 1 (2.15 +/- 0.28 vs 1.7 +/- 0.30 MUmol/L), hour 2 (2.3 +/- 0.29 vs 1.8 +/- 0.32 MUmol/L), hour 3 (2.4 +/- 0.34 vs 1.58 +/- 0.19 MUmol/L), and hour 4 (2.51 +/- 0.33 vs 1.5 +/- 0.12 MUmol/L) (all P < .05) following the high-fat diet as compared with the baseline postprandial response. In conclusion, a short-term, high-fat diet does not increase fasting plasma TMAO concentrations but appears to increase postprandial TMAO concentrations in healthy, nonobese, young men. Future studies are needed to determine the mechanisms responsible for these observations. PMID- 26265296 TI - Anthraquinone dyes for superhydrophobic cotton. AB - Water-repellent, self-cleaning and stain resistant textiles are of interest for industrial applications. Anthraquinone reactive dyes were covalently grafted onto cotton fabric surfaces obtaining bright colors with good wash-fastness properties and giving rise to breathable superhydrophobic textiles with self-cleaning properties. PMID- 26265297 TI - Localized population divergence of vervet monkeys (Chlorocebus spp.) in South Africa: Evidence from mtDNA. AB - OBJECTIVE: Vervet monkeys are common in most tree-rich areas of South Africa, but their absence from grassland and semi-desert areas of the country suggest potentially restricted and mosaic local population patterns that may have relevance to local phenotype patterns and selection. A portion of the mitochondrial DNA control region was sequenced to study patterns of genetic differentiation. METHODS: DNA was extracted, and mitochondrial DNA sequences were obtained from 101 vervet monkeys at 15 localities, which represent both an extensive (widely across the distribution range) and intensive (more than one troop at most of the localities) sampling strategy. Analyses utilized Arlequin 3.1, MEGA 6, BEAST v1.5.2, and Network V3.6.1. RESULTS: The dataset contained 26 distinct haplotypes, with six populations fixed for single haplotypes. Pairwise P distance among population pairs showed significant differentiation among most population pairs, but with nonsignificant differences among populations within some regions. Populations were grouped into three broad clusters in a maximum likelihood phylogenetic tree and a haplotype network. These clusters correspond to i) north-western, northern, and north-eastern parts of the distribution range as well as the northern coastal belt; ii) central areas of the country; and iii) southern part of the Indian Ocean coastal belt and adjacent inland areas. CONCLUSIONS: Apparent patterns of genetic structure correspond to current and past distribution of suitable habitat, geographic barriers to gene flow, geographic distance, and female philopatry. However, further work on nuclear markers and other genomic data are necessary to confirm these results. PMID- 26265298 TI - Imidazolin-2-ylidenaminophosphines as Highly Electron-Rich Ligands for Transition Metal Catalysts. AB - A variety of chemical transformations benefit from the use of strong electron donating ancillary ligands, such as alkylphosphines or N-heterocyclic carbenes when electron-rich metal centers are required. Herein, we describe a facile and highly modular access to monodentate and bidentate imidazolin-2-ylidenamino substituted phosphines. Evaluation of the phosphine's electronic properties substantiate that the formal replacement of alkyl or aryl groups by imidazolin-2 ylidenamino groups dramatically enhance their donor ability beyond that of alkylphosphines and even N-heterocyclic carbenes. The new phosphines have been coordinated onto palladium(II) centers, and the beneficial effect of the novel substitution patterns has been explored by using the corresponding complexes in the palladium-catalyzed Suzuki-Miyaura cross-coupling reaction of non-activated aryl chloride substrates. PMID- 26265299 TI - Long-term trajectories of positive and negative symptoms in first episode psychosis: A 10year follow-up study in the OPUS cohort. AB - OBJECTIVE: Knowledge about course of illness can help clinicians to develop effective interventions and improve treatment outcomes. The goal of this study was to construct positive and negative symptom trajectories based on structured clinical assessments collected over 10years within a cohort of people with first episode psychosis. METHOD: A cohort of 496 people with first episode psychosis (ICD-10, F20-28) originally recruited for the OPUS study (1998-2000) and treated in community psychiatric services were rated on clinical symptoms at 5 different occasions across ten years. Psychopathology was assessed using the Scales for Assessment of Positive and Negative Symptoms. Symptom trajectories were constructed using Latent Class Analysis. RESULTS: Five distinct trajectories were identified for positive symptoms (response - 47%, delayed response - 12%, relapse - 15%, non-response - 13% and episodic response - 13%). Four distinct trajectories were identified for negative symptoms (response - 28%, delayed response - 19%, relapse - 26% and non-response - 27%). Multivariable regression analysis of baseline characteristics identified that longer duration of untreated psychosis (OR 1.27-1.47, p<0.05) and substance abuse (OR 3.47-5.90, p<0.01) were associated with poorer positive symptom trajectories (higher levels of psychotic symptoms) while poor social functioning (OR 1.34-5.55, p<0.05), disorganized symptoms (OR 2.01-2.38, p<0.05) and schizophrenia diagnosis (OR 5.70-8.86, p<0.05) were associated with poorer negative symptom trajectories (higher levels of negative symptoms). A proportion of people displayed significant changes in symptoms several years after diagnosis. CONCLUSIONS: Trajectories of illness for positive and negative symptoms were heterogeneous among people with first episode psychosis. Positive symptoms showed a general pattern of reduction and stabilization over time while negative symptoms typically showed less variation over the ten years. Results have implications for the focus, timing and length of interventions in first episode psychosis. PMID- 26265300 TI - Obesity and anxiety during pregnancy and postpartum: A systematic review. AB - BACKGROUND: Obesity and anxiety during the perinatal period are common and associated with poor health outcomes for the mother and the child. Despite the well-documented health risks of both pregnancy obesity and anxiety, associations between the two have rarely been explored. With this review we aim to provide a systematic overview of the current state of evidence concerning associations between ante- and postnatal anxiety and pregnancy obesity, excessive gestational weight gain, and postpartum weight retention. METHODS: We conducted a systematic literature search in PubMed, Web of Science, and PsychINFO. RESULTS: 13 Records matched our inclusion criteria. Five out of seven studies focusing on pregnancy obesity and anxiety suggest a positive association with ante- or postnatal anxiety. Surprisingly, no study examined anxiety disorders according to DSM and it remains unknown whether anxiety symptomatology reaches clinical relevance. Results from a small number of life-style intervention studies (n=3) suggest that interventions could benefit from a stronger focus on mental health. There were not enough studies on associations between excessive gestational weight gain (n=2) or postpartum weight retention (n=3) and anxiety making it difficult to draw conclusions about possible associations. LIMITATION: The number of included studies is rather small and studies were included irrespective of the study quality which might limit the generalizability of the results. CONCLUSIONS: The majority of the included studies suggest that obese pregnant women might constitute a subgroup that is especially vulnerable for comorbid anxiety and in need of targeted psychological support. However, further high-quality studies, particularly including anxiety disorders, are needed. PMID- 26265301 TI - "Who Is My Neighbor?" Global Neurosurgery in a Non-Zero-Sum World. PMID- 26265302 TI - Profile of a Dictator. Could Hitler's Political Decisions Have Been Influenced by His State of Health? PMID- 26265303 TI - Neurosurgery Initiatives in Global Health. PMID- 26265304 TI - Excitatory orexinergic innervation of rat nucleus incertus--Implications for ascending arousal, motivation and feeding control. AB - Orexin/hypocretin peptides play a central role in the integrated control of feeding/reward and behavioural activation, principally via interactions with other neural systems. A brainstem area involved in behavioural activation is the nucleus incertus (NI), located in the posterior ventromedial central grey. Several studies have implicated NI in control of arousal/stress and reward/feeding responses. Orexin receptor mRNA expression identifies NI as a putative target of orexin modulation. Therefore, in this study we performed neural tract-tracing and immunofluorescence staining to characterise the orexinergic innervation of NI. Our results indicate a convergent innervation of the NI area by different orexin neuron populations, with an abundance of orexin-A containing axons making putative synaptic contacts with relaxin-3-positive NI neurons. The influence of orexin-A on NI neuron activity was investigated using patch-clamp recordings. Orexin-A depolarised the majority (64%) of recorded neurons and this effect was maintained in the presence of tetrodotoxin and glutamate and GABA receptor antagonists, indicating a likely postsynaptic action. Voltage-clamp experiments revealed that in 'type I' NI neurons comprising relaxin 3-positive cells, orexin-A acted via L-type calcium channels, whereas in 'type II' relaxin-3-negative neurons, activation of a sodium/calcium exchanger was involved. A majority of the orexin-A sensitive neurons tested for the presence of orexin receptor mRNA, were OX2 mRNA-positive. Immunohistochemical staining for putative orexin receptors on NI neurons, confirmed stronger expression of OX2 than OX1 receptors. Our data demonstrate a strong influence of orexin-A on NI neurons, consistent with an important role for this hypothalamic/tegmental circuit in the regulation of arousal/vigilance and motivated behaviours. PMID- 26265305 TI - Sonography of the chest wall: A pictorial essay. AB - Ultrasound (US) is increasingly being used as the first-line imaging modality for investigating the chest wall for soft tissue and bony lesions. This article describes the technique used for the US examination, the relevant chest-wall anatomy, and the appearances on US scanning of pathologic entities either unique to or common in the region of the chest wall. PMID- 26265307 TI - Development of an enzymatic assay system of D-lactate using D-lactate dehydrogenase and a UV-LED fluorescent spectrometer. AB - In this study, we aimed to develop a new enzymatic assay system of d-lactate with good precision, accuracy, and sensitivity for the determination of D-lactate concentrations in rat serum. D-Lactate dehydrogenase (D-LDH) was utilized to catalyze D-lactate and NAD(+) to pyruvate and NADH, respectively. The generated NADH was excited by using a 340-nm UV-light-emitting diode (LED), and the fluorescence at 491 nm was detected to determine the concentration of D-lactate in rat serum. The optics, consisting of the sample cuvette, were set on three dimensional stages to receive the most intensive fluorescence signal into the spectrometer. The optimal conditions of the D-LDH reaction were pH 8.5 and 25 degrees C for 90 min. The results showed that the new D-lactate assay system had good linearity (R(2)=0.9964) in the calibration range from 5 to 150 MUM. Intra day and inter-day accuracies were in the range of 103.96-109.09% and 102.84 104.59%, respectively, and the intra-day and inter-day precision was 4.28-6.82% and 4.04-12.40%, respectively. Finally, serum D-lactate concentrations determined by the proposed enzymatic assay system were compared with those obtained by a conventional HPLC method. The newly developed D-lactate assay system could detect 10-15 samples in 90 min, whereas the HPLC method could detect only one sample over the same time period. PMID- 26265306 TI - Hypersensitivity to intravenous iron: classification, terminology, mechanisms and management. AB - Intravenous (IV) iron therapy is widely used in iron deficiency anaemias when oral iron is not tolerated or ineffective. Administration of IV-iron is considered a safe procedure, but severe hypersensitivity reactions (HSRs) can occur at a very low frequency. Recently, new guidelines have been published by the European Medicines Agency with the intention of making IV-iron therapy safer; however, the current protocols are still non-specific, non-evidence-based empirical measures which neglect the fact that the majority of IV-iron reactions are not IgE-mediated anaphylactic reactions. The field would benefit from new specific and effective methods for the prevention and treatment of these HSRs, and the main goal of this review was to highlight a possible new approach based on the assumption that IV-iron reactions represent complement activation-related pseudo-allergy (CARPA), at least in part. The review compares the features of IV iron reactions to those of immune and non-immune HSRs caused by a variety of other infused drugs and thus make indirect inferences on IV-iron reactions. The process of comparison highlights many unresolved issues in allergy research, such as the unsettled terminology, multiple redundant classifications and a lack of validated animal models and lege artis clinical studies. Facts and arguments are listed in support of the involvement of CARPA in IV-iron reactions, and the review addresses the mechanism of low reactogenic administration protocols (LRPs) based on slow infusion. It is suggested that consideration of CARPA and the use of LRPs might lead to useful new additions to the management of high-risk IV-iron patients. PMID- 26265308 TI - Risk profile for osteoradionecrosis of the mandible in the IMRT era. AB - BACKGROUND: The risk for osteoradionecrosis (ORN) of the mandible is positively related to bone volume exposed to > ~ 60 Gy. We hypothesized that in combined treatment, surgery may also be a risk factor. PATIENTS AND METHODS: The impact of mandibular surgery on ORN in locally disease-free IMRT cohorts was retrospectively analyzed. RESULTS: Between October 2002 and October 2013, 531 of 715 patients with oral cavity cancer (OCC), mesopharyngeal cancer (MC), or salivary gland tumor were treated with the mandible bone exposed to ~ > 60 Gy (mean follow-up, 38 months; 7-143 months). Of the 531 patients, 36 developed ORN (7 %; 1.5 % with grade 3-4). The ORN rate in definitive IMRT MC (16/227) and in postoperative IMRT OCC patients with no mandibular surgery (3/46) was 7 % each; in OCC patients with mandibular surgery the rate was 29 % (15/60, p = 0.002). Marginal or periosteal bone resection was found to be a high risk factor (39 %, vs. 7 % followed by segmental or no resection, p < 0.0001). CONCLUSION: Marginal or periosteal bone resection of the mandible was identified as the highest ORN risk factor in our IMRT cohort. PMID- 26265309 TI - Mechanistic Understanding of the Plasmonic Enhancement for Solar Water Splitting. AB - H2 generation by solar water splitting is one of the most promising solutions to meet the increasing energy demands of the fast developing society. However, the efficiency of solar-water-splitting systems is still too low for practical applications, which requires further enhancement via different strategies such as doping, construction of heterojunctions, morphology control, and optimization of the crystal structure. Recently, integration of plasmonic metals to semiconductor photocatalysts has been proved to be an effective way to improve their photocatalytic activities. Thus, in-depth understanding of the enhancement mechanisms is of great importance for better utilization of the plasmonic effect. This review describes the relevant mechanisms from three aspects, including: i) light absorption and scattering; ii) hot-electron injection and iii) plasmon induced resonance energy transfer (PIRET). Perspectives are also proposed to trigger further innovative thinking on plasmonic-enhanced solar water splitting. PMID- 26265310 TI - Dominance of a Rhizopogon sister species corresponds to forest age structure. AB - Rhizopogon vesiculosus and Rhizopogon vinicolor are sister species of ectomycorrhizal fungi that associate exclusively with Douglas-fir (DF). They form tuberculate mycorrhizas and they can be easily distinguished using molecular tools. We are not aware of studies relating their relative abundance in forests with different age classes. Our objective was to determine whether a change in the number or relative abundance of R. vesiculosus and R. vinicolor tubercules and genotypes was related to a change in the percent of DF in a regenerating phase (<50 years old). R. vesiculosus and R. vinicolor were located by excavating tuberculate mycorrhizas from the forest floor. A DNA Alu1 digest was used to distinguish between the two species. Microsatellite markers were used to identify genotypes. The number of R. vesiculosus tubercules correlated positively with an increasing proportion of DF in a regenerating phase, while the number of R. vinicolor tubercules was similar across all forest age structures. The number of R. vesiculosus genotypes did not correlate with forest age structure, whereas the number of R. vinicolor genotypes showed a negative relationship with an increasing proportion of DF in a regenerating phase. When the numbers of R. vesiculosus tubercules and genotypes were expressed as a relative abundance of the two species, there was a positive correlation with an increasing proportion of DF in a regenerating phase for both genotypes and tubercules. Our results suggest that the degree of DF regeneration or ecosystem factors related to DF regeneration affect the population dynamics of R. vesiculosus and R. vinicolor differently. PMID- 26265311 TI - Pain-related anxiety mediates the relationship between depressive symptoms and pain interference in veterans with hepatitis C. AB - OBJECTIVE: Depression and chronic pain are common in persons chronically infected with the hepatitis C virus (HCV), although little is known about the rate of co occurrence or mechanisms by which they are associated. We evaluated whether pain related anxiety mediates the relationship between depressive symptoms and pain related physical functioning in patients with HCV. METHODS: Patients with HCV (n=175) completed self-report measures assessing demographic characteristics, pain-related function and mental health. Path analyses examined direct effects of cognitive-affective and somatic symptoms of depression on pain interference and indirect effects of these relationships via four subscales of the Pain Anxiety Symptoms Scale-20. RESULTS: Cognitive-affective and somatic symptoms of depression were positively and significantly related to pain interference. Pain related anxiety mediated the relationship between both cognitive-affective and somatic symptoms of depression, and this mediation was predominantly accounted for by the escape-avoidance component of pain-related anxiety. CONCLUSIONS: Findings indicate a potential mediating role of pain-related anxiety, particularly escape-avoidance anxiety, on the relationship between depression and pain interference in patients with HCV. These findings suggest that escape avoidance anxiety may be a particularly germane target for treatment in patients with HCV and chronic pain, particularly when depression, with characteristic features of withdrawal and inhibition, is a comorbid condition. PMID- 26265313 TI - A community-based approach to new antibiotic discovery. AB - The Community for Open Antimicrobial Drug Discovery aims to tap into the potential of the millions of compounds distributed around laboratories globally to be a source of new antibiotic leads by offering free screening for antimicrobial properties, with no strings attached. PMID- 26265314 TI - 'I have the world's best job' - staff experience of the advantages of caring for older people. AB - RATIONALE: Besides a growing demand for safe high-quality care for older people, long-term care (LTC) often struggles to recruit appropriately qualified nursing staff. Understanding what LTC staff value in their work may contribute to a more comprehensive understanding of what can attract staff and support person-centred care. AIM: To explore staff experience of the advantages of working in LTC settings for older people. METHODS: Narrative descriptions of 85 LTC staff in Ireland, the Netherlands and Sweden on what they value in their work were analysed with qualitative content analysis. ETHICS: Ethical approval was obtained according to the requirements of each country, and participants provided informed consent prior to the individual interviews. FINDINGS: Working in LTC signifies bonding with the older people residing there, their next of kin and the team members. It means autonomy in one's daily tasks amalgamated with being a part of an affirmative team. Participants reported a sense of accomplishment and fulfilment; caring meant consideration and recognition of the older people and the relationships formed, which provided for professional and personal growth. The sharing of compassion between staff and residents indicated reciprocity of the relationship with residents. STUDY LIMITATIONS: The findings may be transferable to LTC in general although they address only the positive aspects of caring for older people and only the experiences of those staff who had consented to take part in the study. CONCLUSIONS: The findings add to what underpins the quality of care in nursing homes: compassion in the nurse-resident relationship and person-centred care in LTC. They indicate reciprocity in the relations formed that may contribute to the empowerment of older people, but further studies are needed to explore this in more detail. PMID- 26265315 TI - ACS Nano and Nano Letters, Partners in Leading Nanoscience and Nanotechnology. PMID- 26265316 TI - Phenytoin inhibits contractions of rat gastrointestinal and portal vein smooth muscle by inhibiting calcium entry. AB - BACKGROUND: Phenytoin is widely used as a second-line treatment for status epilepticus. Besides its well-known cardiac pro-arrhythmogenicity, side effects on other organ systems have received less attention. METHODS: This study investigates the effects of phenytoin on gastrointestinal tissue function using an in vitro model of smooth muscle preparations from rats by combining registrations of pharmacological effects on mechanical contractions, electric field potentials, and dynamic intravital fluorescence microscopy. KEY RESULTS: When added to the bathing solution at a concentration of 30 MUM, phenytoin reduced the frequency of spontaneous activity significantly in antrum and portal vein preparations to 72.2 +/- 36.5% (p = 0.022) and 80.7 +/- 24.4% (p = 0.037) of control values, respectively. At a concentration of 100 MUM, the height of spontaneous contractions declined to 9.8 +/- 19.6% (p = 0.005) (antrum), 15.7 +/- 28.2% (p = 0.004) (portal vein), and 31.8 +/- 31.3% (p = 0.005) (colon) in comparison to the control conditions before the application of phenytoin. Depolarization triggered increases in calcium dependent fluorescence signals were reduced by 52.8 +/- 39.1% (p = 0.012) The inhibition of spontaneous activity caused by phenytoin was reduced in the presence of the L-type calcium channel agonist BAY K8644(-). CONCLUSIONS & INFERENCES: Phenytoin exerts strong inhibitory effects on the spontaneous and stimulated contractile activity of smooth muscles from both the upper and lower gastrointestinal tract. The mechanism underlying this effect is not related to the sodium channel blocking activity of phenytoin, but is rather caused by an inhibition of calcium entry through voltage dependent L-type calcium channels. The results of this study should raise vigilance to gastrointestinal complications in patients treated with phenytoin. PMID- 26265317 TI - Visible Light-Triggered On-Demand Drug Release from Hybrid Hydrogels and its Application in Transdermal Patches. AB - On-demand release from stimuli-responsive hydrogels has received great attention due to an increasing clinical need. Here, we have prepared spherical hydrogel beads showing visible light-induced volume change at body temper-ature. By spray injection of the monomer solution using the alginate templ-ating method, hybrid beads of several hundred micrometers, consisting of temperature-responsive poly(N isopropylacrylamide-co-vinyl-2-pyrrolidinone) hydrogel and magnetite nanoparticles (MNP), are produced. MNP dispersed in the hydrogel matrix absorbed visible light and generated heat, increasing the temperature of the matrix and resulting in shrinkage of the beads proportional to light intensity. It is demonstrated that light-induced volume change of dexamethasone-loaded hybrid beads result in on-demand and localized release of the drug by exposure to moderate visible light. As a potential application of the light-sensitive hybrid hydrogel beads, a transdermal patch is developed that incorporates drug-loaded hydrogel beads in multiple drug reservoirs, achieving enhanced release of a model drug when exposed to visible light. This platform should be applicable to on demand, sequential, and long-term release of drugs via light exposure. PMID- 26265318 TI - Studies of the mechanism of an antibacterial peptide (cecropinA-magainin) on methicillin-resistant Staphylococcus aureus membranes. AB - As bacterial resistance becomes increasingly common, a new hybrid peptide, cecropinA-magainin (KWALSKEGPGKFLGKKKKF), has been developed that can kill a broad spectrum of bacteria without damaging human cells. The mechanism of antibacterial toxicity for the hybrid peptides is unknown. Herein, we investigate the localization of the hybrid peptide in methicillin-resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentration was 64 ug/mL. The hybrid peptides could enhance the hydrophobicity of MRSA. Dye leakage experiments showed that the hybrid peptides caused dye leakage from liposomes. The hybrid peptides influenced the permeability of the outer membrane and plasma membrane of MRSA. After cecropinA-magainin treatment of MRSA, the membrane ultrastructure was damaged and the concentration of K+ increased. Ultimately, the peptide destroyed the integrity of the bacterial cell membrane, allowing the dye propidium iodide to enter the cytoplasm. Therefore, the hybrid antibacterial peptide can kill MRSA. PMID- 26265319 TI - More of me! Distinguishing self and reward bias using redundancy gains. AB - Participants show a perceptual bias favoring stimuli associated with the participants themselves over stimuli associated with other people. A major account of this self-bias effect is that self-related information is intrinsically rewarding, and that high-reward stimuli have enhanced perceptual processing. Here we used redundancy gains to examine the relations between self bias and reward, and whether self and reward biases modulate common levels of stimulus integration. We demonstrated that the self-association bias increases when more than one exemplar of the stimulus is presented (i.e., when participants are exposed to redundant stimuli). The larger self-bias effects for redundant than for single stimuli arose at both perceptual and conceptual levels of representation (respectively, for identical and nonidentical stimuli associated with the same category). In contrast, high-reward stimuli did not affect perceptual redundancy gains with identical shapes, but they did affect redundancy gains with nonidentical stimuli associated with the same category. The strong redundancy effects with self-related stimuli are consistent with self associations modulating stimulus integration at both perceptual and conceptual levels, whereas reward only modulated higher-level conceptual processes (with nonidentical stimuli). The data provide two novel theoretical advances, by showing that (i) self association modulates both early perceptual coding and higher-level conceptual coding, whereas reward only affects the higher-level process, and (ii) self bias can not be reduced simply to differential effects of reward. PMID- 26265312 TI - Strategies to increase nitric oxide signalling in cardiovascular disease. AB - Nitric oxide (NO) is a key signalling molecule in the cardiovascular, immune and central nervous systems, and crucial steps in the regulation of NO bioavailability in health and disease are well characterized. Although early approaches to therapeutically modulate NO bioavailability failed in clinical trials, an enhanced understanding of fundamental subcellular signalling has enabled a range of novel therapeutic approaches to be identified. These include the identification of: new pathways for enhancing NO synthase activity; ways to amplify the nitrate-nitrite-NO pathway; novel classes of NO-donating drugs; drugs that limit NO metabolism through effects on reactive oxygen species; and ways to modulate downstream phosphodiesterases and soluble guanylyl cyclases. In this Review, we discuss these latest developments, with a focus on cardiovascular disease. PMID- 26265320 TI - A Novel Arginase Inhibitor Derived from Scutellavia indica Restored Endothelial Function in ApoE-Null Mice Fed a High-Cholesterol Diet. AB - Elevated endothelial arginase activity decreases nitric oxide (NO) production by competing with the substrate l-arginine, previously reported, and reciprocally regulating endothelial nitric oxide synthase (eNOS) activity. Thus, arginase inhibitors may help treat vascular diseases associated with endothelial dysfunction. A screening of metabolites from medicinal plants revealed that (2S) 5,2',5'-trihydroxy-7,8-dimethoxy flavanone (TDF) was a noncompetitive inhibitor of arginase. We investigated whether TDF reciprocally regulated endothelial NO production and its possible mechanism. TDF noncompetitively inhibited arginase I and II activity in a dose-dependent manner. TDF incubation decreased arginase activity and increased NO production in human umbilical vein endothelial cells and isolated mouse aortic vessels and reduced reactive oxygen species (ROS) generation in the endothelium of the latter. These TDF-mediated effects were associated with increased eNOS phosphorylation and dimerization but not with changes in protein content. Endothelium-dependent vasorelaxant responses to acetylcholine (Ach) were significantly increased in TDF-incubated aortic rings and attenuated by incubation with soluble guanylyl cyclase inhibitor. Phenylephrine-induced vasoconstrictor responses were markedly attenuated in TDF treated vessels from wild-type mice. In atherogenic-prone ApoE(-/-) mice, TDF attenuated the high-cholesterol diet (HCD)-induced increase in arginase activity, which was accompanied by restoration of NO production and reduction of ROS generation. TDF incubation induced eNOS dimerization and phosphorylation at Ser1177. In addition, TDF improved Ach-dependent vasorelaxation responses and attenuated U46619-dependent contractile responses but did not change sodium nitroprusside-induced vasorelaxation or N-NAME-induced vasoconstriction. The findings suggest that TDF may help treat cardiovascular diseases by reducing pathophysiology derived from HCD-mediated endothelial dysfunction. PMID- 26265321 TI - The Prodrug 4-Chlorokynurenine Causes Ketamine-Like Antidepressant Effects, but Not Side Effects, by NMDA/GlycineB-Site Inhibition. AB - Currently approved antidepressant drug treatment typically takes several weeks to be effective. The noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist ketamine has shown efficacy as a rapid-acting treatment of depression, but its use is associated with significant side effects. We assessed effects following blockade of the glycineB co-agonist site of the NMDA receptor, located on the GluN1 subunit, by the selective full antagonist 7-chloro-kynurenic acid (7-Cl KYNA), delivered by systemic administration of its brain-penetrant prodrug 4 chlorokynurenine (4-Cl-KYN) in mice. Following administration of 4-Cl-KYN, 7-Cl KYNA was promptly recovered extracellularly in hippocampal microdialysate of freely moving animals. The behavioral responses of the animals were assessed using measures of ketamine-sensitive antidepressant efficacy (including the 24 hour forced swim test, learned helplessness test, and novelty-suppressed feeding test). In these tests, distinct from fluoxetine, and similar to ketamine, 4-Cl KYN administration resulted in rapid, dose-dependent and persistent antidepressant-like effects following a single treatment. The antidepressant effects of 4-Cl-KYN were prevented by pretreatment with glycine or the alpha amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 2,3 dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX). 4-Cl-KYN administration was not associated with the rewarding and psychotomimetic effects of ketamine, and did not induce locomotor sensitization or stereotypic behaviors. Our results provide further support for antagonism of the glycineB site for the rapid treatment of treatment-resistant depression without the negative side effects seen with ketamine or other channel-blocking NMDA receptor antagonists. PMID- 26265322 TI - Profiling of the small RNA populations in human testicular germ cell tumors shows global loss of piRNAs. AB - BACKGROUND: Small non-coding RNAs play essential roles in gene regulation, however, the interplay between RNA groups, their expression levels and deregulations in tumorigenesis requires additional exploration. In particular, a comprehensive analysis of microRNA (miRNA), PIWI-interacting RNAs (piRNAs), and tRNA-derived small RNAs in human testis and testicular germ cell tumor (TGCT) is lacking. RESULTS: We performed small RNA sequencing on 22 human TGCT samples from 5 histological subtypes, 3 carcinoma in situ, and 12 normal testis samples. miRNA was the most common group among the sequences 18-24 nt in length and showed histology-specific expression. In normal samples, most sequences 25-31 nucleotides in length displayed piRNA characteristics, whereas a large proportion of the sequences 32-36 nt length was derived from tRNAs. Expression analyses of the piRNA population demonstrated global loss in all TGCT subtypes compared to normal testis. In addition, three 5' small tRNA fragments and 23 miRNAs showed significant (p < 10(-6)) differential expression in cancer vs normal samples. CONCLUSIONS: We have documented significant changes in the small RNA populations in normal adult testicular tissue and TGCT samples. Although components of the same pathways might be involved in miRNA, piRNA and tRNA-derived small RNA biogenesis, our results showed that the response to the carcinogenic process differs between these pathways, suggesting independent regulation of their biogenesis. Overall, the small RNA deregulation in TGCT provides new insight into the small RNA interplay. PMID- 26265323 TI - Causes of elevated intraocular pressure following implantation of phakic intraocular lenses for myopia. AB - The purpose of this study is to present the causes and visual acuity outcomes in patients with elevated intraocular pressure (IOP) following implantable collamer lens (ICL) implantation. A chart review identified patients who developed high IOP at any postoperative examination and a minimum follow-up period of 3 months after ICL implantation. Data are reported out to 6 months postoperatively. Outcome measures included causes of elevated IOP, best-corrected visual acuity (BCVA) at last visit, number of glaucoma medications, other interventions, and glaucomatous damage. Elevated IOP occurred in 58 (10.8 %) of 534 eyes that received ICL. The mean age was 28 +/- 7.2 years. The preoperative IOP was 16.3 +/ 1.2 mmHg. Elevated IOP most commonly occurred on the first postoperative day (23/58 (39.7 %) eyes) due to retained viscoelastic. This was followed by steroid response in 22/58 (37.9 %) eyes at 2-4 weeks postoperatively. IOP elevation in 6 (10.3 %) eyes was related to high ICL vault and pupillary block, and in 4 (6.9 %) eyes due to synechial angle closure. At last visit, BCVA was 20/40 or better in 56/58 (96.6 %) eyes, and 5/58 (8.6 %) eyes remained on glaucoma medications due to persistent steroid response (2 eyes), synechial angle closure glaucoma (1 eye), and other causes (2 eyes). One eye showed glaucomatous damage. Two eyes with high vault and elevated IOP underwent ICL explantation. There is a moderate risk of transiently developing elevated IOP after ICL implantation. Thorough removal of viscoelastic and use of anti-glaucoma medications during steroid use will reduce the majority of cases with postoperative IOP elevation. PMID- 26265324 TI - Optical coherence tomography and pathological myopia: an update of the literature. AB - The purpose of this paper is to give an updated review of the last clinical entities in pathological myopia proposed by means of new generation optical coherence tomography (OCT), including enhanced depth imaging (EDI-OCT) and swept source OCT (SS-OCT). PubMed and Google engine search were carried out using the terms "pathological myopia" associated with "coherence tomography," "enhanced depth imaging," and "swept source OCT." Latest publications up to Jan 2015 about myopia-related complications, including open-angle chronic glaucoma, peripapillary retinal changes, acquired macular diseases, and choroidal neovascularization, have been reviewed. New OCT technologies have led to a greater insight in pathophysiology of high-grade myopia. However, further investigation is needed in order to prevent irreversible visual loss and optic nerve damage. PMID- 26265325 TI - Structure and content components of self-management interventions that improve health-related quality of life in people with inflammatory bowel disease: a systematic review, meta-analysis and meta-regression. AB - AIMS AND OBJECTIVES: The purpose of this review was to identify and categorise the components of the content and structure of effective self-management interventions for patients with inflammatory bowel disease. BACKGROUND: Inflammatory bowel diseases are chronic gastrointestinal disorders impacting health-related quality of life. Although the efficacy of self-management interventions has been demonstrated in previous studies, the most effective components of the content and structure of these interventions remain unknown. DESIGN: A systematic review, meta-analysis and meta-regression of randomised controlled trials was used. METHODS: A systematic search of six electronic databases, including Pubmed, Embase, Cochrane central register of controlled trials, Web of Science, Cumulative Index of Nursing and Allied Health Literature and Chinese Biomedical Literature Database, was conducted. Content analysis was used to categorise the components of the content and structure of effective self management interventions for inflammatory bowel disease. Clinically important and statistically significant beneficial effects on health-related quality of life were explored, by comparing the association between effect sizes and various components of self-management interventions such as the presence or absence of specific content and different delivery methods. RESULTS: Fifteen randomised controlled trials were included in this review. Distance or remote self management interventions demonstrated a larger effect size. However, there is no evidence for a positive effect associated with specific content component of self management interventions in adult patients with inflammatory bowel disease in general. CONCLUSIONS: The results showed that self-management interventions have positive effects on health-related quality of life in patients with inflammatory bowel disease, and distance or remote self-management programmes had better outcomes than other types of interventions. RELEVANCE TO CLINICAL PRACTICE: This review provides useful information to clinician and researchers when determining components of effective self-management programmes for patients with inflammatory bowel disease. More high-quality randomised controlled trials are needed to test the results. PMID- 26265326 TI - Development and initial validation of the Parental PELICAN Questionnaire (PaPEQu) -an instrument to assess parental experiences and needs during their child's end of-life care. AB - AIM: To develop and test the Parental PELICAN Questionnaire, an instrument to retrospectively assess parental experiences and needs during their child's end-of life care. BACKGROUND: To offer appropriate care for dying children, healthcare professionals need to understand the illness experience from the family perspective. A questionnaire specific to the end-of-life experiences and needs of parents losing a child is needed to evaluate the perceived quality of paediatric end-of-life care. DESIGN: This is an instrument development study applying mixed methods based on recommendations for questionnaire design and validation. METHOD: The Parental PELICAN Questionnaire was developed in four phases between August 2012-March 2014: phase 1: item generation; phase 2: validity testing; phase 3: translation; phase 4: pilot testing. Psychometric properties were assessed after applying the Parental PELICAN Questionnaire in a sample of 224 bereaved parents in April 2014. Validity testing covered the evidence based on tests of content, internal structure and relations to other variables. RESULTS: The Parental PELICAN Questionnaire consists of approximately 90 items in four slightly different versions accounting for particularities of the four diagnostic groups. The questionnaire's items were structured according to six quality domains described in the literature. Evidence of initial validity and reliability could be demonstrated with the involvement of healthcare professionals and bereaved parents. CONCLUSION: The Parental PELICAN Questionnaire holds promise as a measure to assess parental experiences and needs and is applicable to a broad range of paediatric specialties and settings. Future validation is needed to evaluate its suitability in different cultures. PMID- 26265327 TI - Clinical usefulness and validity of robotic measures of reaching movement in hemiparetic stroke patients. AB - BACKGROUND: Various robotic technologies have been developed recently for objective and quantitative assessment of movement. Among them, robotic measures derived from a reaching task in the KINARM Exoskeleton device are characterized by their potential to reveal underlying motor control in reaching movements. The aim of this study was to examine the clinical usefulness and validity of these robot-derived measures in hemiparetic stroke patients. METHODS: Fifty-six participants with a hemiparetic arm due to chronic stroke were enrolled. The robotic assessment was performed using the Visually Guided Reaching (VGR) task in the KINARM Exoskeleton, which allows free arm movements in the horizontal plane. Twelve parameters were derived based on motor control theory. The following clinical assessments were also administered: the proximal upper limb section in the Fugl-Meyer Assessment (FMA-UE(A)), the proximal upper limb part in the Stroke Impairment Assessment Set (SIAS-KM), the Modified Ashworth Scale for the affected elbow flexor muscles (MAS elbow), and seven proximal upper limb tasks in the Wolf Motor Function Test (WMFT). To explore which robotic measures represent deficits of motor control in the affected arm, the VGR parameters in the paretic arm were compared with those in the non-paretic arm using the Wilcoxon signed rank test. Then, to explore which VGR parameters were related to overall motor control regardless of the paresis, correlations between the paretic and non-paretic arms were examined. Finally, to investigate the relationships between the robotic measures and the clinical scales, correlations between the VGR parameters and clinical scales were investigated. Spearman's rank correlation coefficients were used for all correlational analyses. RESULTS: Eleven VGR parameters on the paretic side were significantly different from those on the non-paretic side with large effect sizes (|effect size| = 0.76-0.87). Ten VGR parameters correlated significantly with FMA-UE(A) (|r| = 0.32-0.60). Eight VGR parameters also showed significant correlations with SIAS-KM (|r| = 0.42-0.49), MAS elbow (|r| = 0.44 0.48), and the Functional Ability Scale of the WMFT (|r| = 0.52-0.64). CONCLUSIONS: The robot-derived measures could successfully differentiate between the paretic arm and the non-paretic arm and were valid in comparison to the well established clinical scales. PMID- 26265328 TI - Sustained low influenza vaccination in health care workers after H1N1 pandemic: a cross sectional study in an Italian health care setting for at-risk patients. AB - BACKGROUND: Despite consistent recommendations by all Public Health Authorities in support of annual influenza vaccination for at-risk categories, there is still a low uptake of influenza vaccine in these groups including health care workers (HCWs). Aim of this observational two-phase study was to estimate the immunization rates for influenza in four subsequent seasons and for pandemic H1N1 influenza in HCWs of a University Hospital, and to investigate its distribution pattern and the main determinants of immunization. Phase 1 data collection was performed in 2009-2010, during the peak of H1N1 pandemic. Phase 2 data collection, aimed to investigate seasonal influenza vaccination coverage in the three seasons after pandemic, was performed in 2012-2013. METHODS: The overall H1N1 vaccination rate was derived by the Hospital immunization registry. In 2010, the personnel of three Departments (Infectious Diseases, Pediatrics and Gynecology/Obstetrics) completed a survey on influenza. A second-phase analysis was performed in 2012 to investigate influenza vaccination coverage in three consecutive seasons. RESULTS: The first-phase survey showed a low coverage for influenza in all categories (17 %), with the lowest rate in nurses (8.1 %). A total of 37 % of health care workers received H1N1 vaccine, with the highest rate among physicians and the lowest in nurses. H1N1 vaccination was closely related to the Department, being higher in the Department of Infectious Diseases (53.7 %) and Pediatrics (42.4 %) than in Gynecology/Obstetrics (8.3 %). The second-phase survey showed the lowest rate of influenza vaccination in 2012/13 season. The main reasons for not being vaccinated were "Unsure of the efficacy of vaccine" and "Feel not at-risk of getting influenza or its complications". Despite recommendations, influenza vaccine uptake remains poor. CONCLUSION: Immunization is largely perceived as a personal protection rather than a measure needed to prevent disease spreading to at-risk patients. Compulsory vaccination against influenza should be considered as a possible strategy, at least in health institutions where at-risk patients are admitted. PMID- 26265332 TI - Correction. PMID- 26265331 TI - 2015 ACTERIA Prizes Awarded by EFIS. PMID- 26265337 TI - The Self-Presentation Motives for Physical Activity Questionnaire: Instrument Development and Preliminary Construct Validity Evidence. AB - With the aim of advancing the literature on impression management in physical activity settings, we developed a theoretically derived 2 by 2 instrument that was designed to measure different types of context-specific self-presentation motives. Following item generation and expert review (Study 1), the instrument was completed by 206 group exercise class attendees (Study 2) and 463 high school physical education students (Study 3). Our analyses supported the intended factor structure (i.e., reflecting acquisitive-agentic, acquisitive-communal, protective agentic, and protective-communal motives). We found some support for construct validity, and the self-presentation motives were associated with variables of theoretical and applied interest (e.g., impression motivation and construction, social anxiety, social and achievement goals, efficacy beliefs, engagement). Taken together, the results indicate that the Self-presentation Motives for Physical Activity Questionnaire (SMPAQ) may be useful for measuring various types of self-presentation motives in physical activity settings. PMID- 26265338 TI - Patterns of Change in Psychological Variables Leading up to Competition in Superior Versus Inferior Performers. AB - The study explored patterns of change in a number of potentially performance related variables (i.e., fatigue, social support, self-efficacy, autonomous motivation, mental skills) during the lead-up to a competitive triathlon, and whether these patterns of change differed for relatively superior versus inferior performers. Forty-two triathletes completed an inventory measuring the study variables every other day during a 2-week period leading up to competition. Performance was assessed using participants' race time, and using a self referenced relative score compared with personal best times. Multilevel growth curve analyses revealed significant differences in growth trajectories over the 2 week period in mental skills use, social support, and fatigue. The results provide novel insight into how athletes' fluctuating psychological state in the 2 weeks before competition may be crucial in determining performance. PMID- 26265339 TI - Antisocial and Prosocial Behavior in Sport: The Role of Motivational Climate, Basic Psychological Needs, and Moral Disengagement. AB - The purpose of this investigation was to examine whether the relationships between contextual factors and basic psychological needs were related to antisocial and prosocial behavior in sport. A two-study project employing Bayesian path analysis was conducted with competitive athletes (Study 1, n = 291; Study 2, n = 272). Coach and teammate autonomy-supportive climates had meaningful direct relations with need satisfaction and prosocial behavior. Coach and teammate controlling climates had meaningful direct relations with antisocial behavior. Need satisfaction was both directly and indirectly related with both prosocial and antisocial behavior, whereas moral disengagement was directly and indirectly related with antisocial behavior. Overall, these findings reflected substantial evidence from the literature on self-determination theory that autonomy-supportive motivational climates are important environmental influences for need satisfaction, and are important correlates of prosocial behavior in sport, whereas controlling coach and teammate climates, along with moral disengagement, were important correlates of antisocial behavior in sport. PMID- 26265340 TI - The Art of Athlete Leadership: Identifying High-Quality Athlete Leadership at the Individual and Team Level Through Social Network Analysis. AB - This research aimed to introduce social network analysis as a novel technique in sports teams to identify the attributes of high-quality athlete leadership, both at the individual and at the team level. Study 1 included 25 sports teams (N = 308 athletes) and focused on athletes' general leadership quality. Study 2 comprised 21 sports teams (N = 267 athletes) and focused on athletes' specific leadership quality as a task, motivational, social, and external leader. The extent to which athletes felt connected with their leader proved to be most predictive for athletes' perceptions of that leader's quality on each leadership role. Also at the team level, teams with higher athlete leadership quality were more strongly connected. We conclude that social network analysis constitutes a valuable tool to provide more insight in the attributes of high-quality leadership both at the individual and at the team level. PMID- 26265341 TI - Injury Risk Estimation Expertise: Cognitive-Perceptual Mechanisms of ACL-IQ. AB - Instrument-based biomechanical movement analysis is an effective injury screening method but relies on expensive equipment and time-consuming analysis. Screening methods that rely on visual inspection and perceptual skill for prognosticating injury risk provide an alternative approach that can significantly reduce cost and time. However, substantial individual differences exist in skill when estimating injury risk performance via observation. The underlying perceptual cognitive mechanisms of injury risk identification were explored to better understand the nature of this skill and provide a foundation for improving performance. Quantitative structural and process modeling of risk estimation indicated that superior performance was largely mediated by specific strategies and skills (e.g., irrelevant information reduction), and independent of domain general cognitive abilities (e.g., mental rotation, general decision skill). These cognitive models suggest that injury prediction expertise (i.e., ACL-IQ) is a trainable skill, and provide a foundation for future research and applications in training, decision support, and ultimately clinical screening investigations. PMID- 26265342 TI - Perfectionism and Burnout in Junior Athletes: A Three-Month Longitudinal Study. AB - Perfectionism in sports has been shown to be associated with burnout in athletes. Whether perfectionism predicts longitudinal changes in athlete burnout, however, is still unclear. Using a two-wave cross-lagged panel design, the current study examined perfectionistic strivings, perfectionistic concerns, and athlete burnout in 101 junior athletes (mean age 17.7 years) over 3 months of active training. When structural equation modeling was employed to test a series of competing models, the best-fitting model showed opposite patterns for perfectionistic strivings and perfectionistic concerns. Whereas perfectionistic concerns predicted increases in athlete burnout over the 3 months, perfectionistic strivings predicted decreases. The present findings suggest that perfectionistic concerns are a risk factor for junior athletes contributing to the development of athlete burnout whereas perfectionistic strivings appear to be a protective factor. PMID- 26265343 TI - Why the Three-Point Rule Failed to Sufficiently Reduce the Number of Draws in Soccer: An Application of Prospect Theory. AB - Incentives guide human behavior by altering the level of external motivation. We apply the idea of loss aversion from prospect theory (Kahneman & Tversky, 1979) to the point reward systems in soccer and investigate the controversial impact of the three-point rule on reducing the fraction of draws in this sport. Making use of the Poisson nature of goal scoring, we compared empirical results with theoretically deduced draw ratios from 24 countries encompassing 20 seasons each (N = 118.148 matches). The rule change yielded a slight reduction in the ratio of draws, but despite adverse incentives, still 18% more matches ended drawn than expected, t(23) = 11.04, p < .001, d = 2.25, consistent with prospect theory assertions. Alternative point systems that manipulated incentives for losses yielded reductions at or below statistical expectation. This provides support for the deduced concept of how arbitrary aims, such as the reduction of draws in the world's soccer leagues, could be more effectively accomplished than currently attempted. PMID- 26265344 TI - Examining Movement-Specific Reinvestment and Performance in Demanding Contexts. AB - Two experiments examined the roles of the dimensions of movement-specific reinvestment (movement self-consciousness and conscious motor processing) on performance under demanding conditions. In Experiment 1, novice golfers practiced a golf putting task and were tested under low- and high-anxiety conditions. Conscious motor processing was not associated with putting proficiency or movement variability; however, movement self-consciousness was positively associated with putting proficiency and appeared to be negatively associated with variability of impact velocity in low-anxiety conditions, but not in high-anxiety conditions. Increased anxiety and effort possibly left few attention resources for movement self-consciousness under high anxiety. In Experiment 2, participants performed a quiet standing task in single- and dual-task conditions. Movement self-consciousness was positively associated with performance when attention demands were low (single task) but not when attention demands were high (dual task). The findings provide insight into the differential influence of the two dimensions of movement-specific reinvestment under demanding conditions. PMID- 26265345 TI - Reappraising Threat: How to Optimize Performance Under Pressure. AB - Competitive situations often hinge on one pressurized moment. In these situations, individuals' psychophysiological states determine performance, with a challenge state associated with better performance than a threat state. But what can be done if an individual experiences a threat state? This study examined one potential solution: arousal reappraisal. Fifty participants received either arousal reappraisal or control instructions before performing a pressurized, single-trial, motor task. Although both groups initially displayed cardiovascular responses consistent with a threat state, the reappraisal group displayed a cardiovascular response more reflective of a challenge state (relatively higher cardiac output and/or lower total peripheral resistance) after the reappraisal manipulation. Furthermore, despite performing similarly at baseline, the reappraisal group outperformed the control group during the pressurized task. The results demonstrate that encouraging individuals to interpret heightened physiological arousal as a tool that can help maximize performance can result in more adaptive cardiovascular responses and motor performance under pressure. PMID- 26265346 TI - Translating DPYD genotype into DPD phenotype: using the DPYD gene activity score. AB - The dihydropyrimidine dehydrogenase enzyme (DPD, encoded by the gene DPYD) plays a key role in the metabolism of fluoropyrimidines. DPD deficiency occurs in 4-5% of the population and is associated with severe fluoropyrimidine-related toxicity. Several SNPs in DPYD have been described that lead to absent or reduced enzyme activity, including DPYD*2A, DPYD*13, c.2846A>T and c.1236G>A/haplotype B3. Since these SNPs differ in their effect on DPD enzyme activity, a differentiated dose adaption is recommended. We propose the gene activity score for translating DPYD genotype into phenotype, accounting for differences in functionality of SNPs. This method can be used to standardize individualized fluoropyrimidine dose adjustments, resulting in optimal safety and effectiveness. PMID- 26265347 TI - Proteomic analysis of aqueous humor proteins associated with cataract development. AB - BACKGROUND: Cataract is one of the most common eye diseases that can further cause blindness. Discovering susceptibility factors contributing to cataract development is helpful in identifying predisposed patients and improving treatment efficacy. Although proteomics technology has been used in study of protein markers related to eye diseases, few were on studies of cataract development. METHODS: To explore cataract-associated susceptibility factors in aqueous humor (AH), a quantitative proteomics study using the iTRAQ methodology was employed to compare AH protein profiles between high myopia patients & controls, glaucoma surgery patients & controls, and vitrectomy surgery patients & controls, respectively. RESULTS: A total of 445 AH proteins were identified, and 210 proteins were differentially expressed between myopia patients and controls, 262 proteins were differentially expressed between glaucoma surgery patients and controls, and 161 proteins were differentially expressed between vitrectomy surgery patients and controls. Among the 445 identified proteins, 77 were considered to be cataract-associated, and 5 of the 77 proteins were randomly selected and confirmed by ELISA assay. Biological functions of these 77 proteins were annotated by GO/pathways analysis. Additionally, 17 proteins were found to be involved in protein-protein interaction networks, 5 of which were associated with nervous system disease and eye diseases including cataract. CONCLUSIONS: The identified candidate protein biomarkers associated with cataract development may lead to more insights into the underlying mechanisms of cataract disease. PMID- 26265348 TI - Optimising plasma levels of clozapine during metabolic interactions: a review and case report with adjunct rifampicin treatment. AB - BACKGROUND: Clozapine is the only licensed medication for treatment-resistant schizophrenia. The metabolism of clozapine is affected by multiple pharmacokinetic interactions, so the co-administration of adjunct medications can have a significant clinical effect. The anti- tuberculosis medication rifampicin is a potent inducer of the cytochrome P450 system and therefore can cause a reduction in the plasma concentration of clozapine. There is limited clinical evidence regarding co-administration of these medications; in particular there is a lack of data regarding the effect on plasma clozapine levels, which is the key factor determining clinical efficacy. This is clinically relevant given evidence of an increased risk of tuberculosis in patients with schizophrenia. CASE PRESENTATION: We present a case of a 28 year old British man with a diagnosis of schizoaffective disorder who presented with persistent psychotic symptoms. He developed a systemic inflammatory condition, diagnosed as tuberculosis, and was commenced on a six month course of treatment that included rifampicin. This case presents comprehensive data to illustrate the effect on clozapine plasma levels of a complete course of tuberculosis therapy. CONCLUSION: This case report provides guidance to clinicians in managing drug interactions between clozapine and rifampicin to enable safe and effective treatment. The co-administration of these medications is likely to increase as the existing underuse of clozapine is recognised whilst the incidence of tuberculosis increases. PMID- 26265349 TI - Anaphylactoid reaction caused by sodium ceftriaxone in two horses experimentally infected by Borrelia burgdorferi. AB - BACKGROUND: Lyme borreliosis is a disease transmitted by ticks to mammals, especially in horses and humans. Caused by a spirochete Borrelia burgdorferi, it can result in lameness, arthritis, carditis, dermatitis and neurological signs. Anaphylactoid reactions are severe responses caused by direct action of substances (drugs, toxins), which can pose risks to life. Still poorly documented in horses, these reactions are caused by the effects of inflammatory mediators such as histamine, kinins and arachidonic acid metabolites. The last two are the most clinically relevant for the species. CASE PRESENTATION: The simultaneous occurrence of anaphylactoid reaction in two horses experimentally infected by Borrelia burgdorferi undergoing intravenous treatment with ceftriaxone sodium is reported. It was administered 4.7 * 10(8) spirochetes intradermal and subcutaneous applications in both horses to evaluate clinical aspects of the Lyme disease, 95 days before the application of sodium ceftriaxone. During the administration, one horse (a gelding) showed immediate and severe anaphylactoid symptoms such as urticaria, dyspnea, tachycardia, and eyelid edema, which were controlled by injecting dexamethasone. After 1 day, it expressed signs of abdominal discomfort, caused by severe bloat, which was treated surgically via celiotomy. Subsequently, this gelding had piroplasmosis and severe anemia, requiring treatment with an antimicrobial and blood transfusion. Second horse (a mare) showed signs of hypotension during the application of the antibiotic, which disappeared only when the application was interrupted. Days after the event, the mare developed moderate large colon bloat, which was treated with medication only. Subsequently the mare was evolved into the prodromal phase of laminitis in one of the forelimbs, which was treated for 10 days with non-steroidal anti inflammatory and rheology modifying drugs and cryotherapy. CONCLUSIONS: From the two cases presented here, it does appear that sodium ceftriaxone can induce anaphylactoid reactions in horses infected by Borrelia burgdorferi, which may evolve into colic syndrome, laminitis and the occurrence of opportunistic infections. However, further evidence should be collected in order to draw definite conclusions. PMID- 26265350 TI - Cavity lining after excavating caries lesions: meta-analysis and trial sequential analysis of randomized clinical trials. AB - OBJECTIVES: After removal of dentine caries lesions, cavity lining has been advocated. Non-clinical data support this approach, but clinical data are sparse and ambiguous. We aimed at evaluating the benefits and harms of cavity lining using meta-analysis and Trial Sequential Analysis. DATA: We included randomized clinical trials comparing restorations without versus with cavity lining for treating primary caries lesions. Only trials reporting failure (defined as need to re-retreat) after >=1 year follow-up were included. Trial selection, data extraction, and risk of bias assessment were conducted independently by two reviewers. We conducted random-effects intention-to-treat and per-protocol meta analyses, and Trial Sequential Analysis to control for random errors. SOURCES: Electronic databases (PubMed, Embase, CENTRAL) were systematically screened, and hand searches and cross-referencing performed. STUDY SELECTION: From 128 studies, three randomized trials (89/130 patients or teeth), all treating primary teeth, were included. The trials had high risk of bias. All trials compared no lining versus calcium hydroxide lining after selective caries removal followed by adhesive restoration. Follow-up was 36 to 53 months. Restoring the cavity without lining did not significantly affect the risk of failure (intention-to-treat relative risk (RR) (95% confidence interval) 0.71 (0.49-1.04), per-protocol RR 0.52 (0.24-1.10). According to Trial Sequential Analysis, no firm evidence was reached. The quality of evidence was very low. CONCLUSIONS: Strong recommendations for using cavity liners are unsubstantiated, but firm evidence for omitting lining is also unavailable. Our findings apply only to primary teeth and calcium hydroxide liner. CLINICAL SIGNIFICANCE: Whilst lining is frequently performed in dental practice, very few randomized clinical trials investigated this issue. The three trials included in this review treated deciduous teeth and did not find lining with calcium hydroxide beneficial. Lining is not supported by sufficient clinical evidence. PMID- 26265351 TI - Heterocyclic Scaffolds in the Design of Peptidomimetic Integrin Ligands: Synthetic Strategies, Structural Aspects, and Biological Activity. AB - The integrin receptors represent valuable targets for therapeutic interventions; being overexpressed in many pathological states, their inhibition can be effective to treat a number of severe diseases. Since integrin functions are mediated by interactions with ECM protein ligands, the inhibition can be achieved by interfering with such interactions using small mimetics of the integrin-ligand recognition motifs (e.g. RGD, LDV, etc.). In this review, we focus on the antagonists with peptideheterocycle hybrid structures. The introduction of well designed scaffolds has met considerable success in the rational design of highly stable, bioavailable, and conformationally defined antagonists. Two main approaches are discussed herein. The first approach is the use of scaffolds external to the main recognition motifs, aimed at improving conformational definition. In the second approach, heterocyclic cores are introduced within the recognition motifs, giving access to libraries of 3D diverse candidate antagonists. PMID- 26265353 TI - Current Understanding of the Mechanisms by which Membrane-Active Peptides Permeate and Disrupt Model Lipid Membranes. AB - Three classes of membrane active peptides (MAPs) are considered in this review: cell penetrating peptides (CPPs); anti-microbial peptides (AMPs), and amyloidal peptides. We summarize both experimental and theoretical results for several representative peptides in these different classes, which highlight commonalities in their interactions with model lipid membranes. While it is clear that no fixed set of mechanisms completely characterize any particular class of MAPs, there is certainly evidence that common mechanisms can be found within and between classes. For example, CPPs appear to undergo rapid translocation across lipid bilayers through small transient pores, which nevertheless appear not to cause persistent damage to membranes. On the other hand, AMPs also show evidence of rapid translocation, but associated with this, is membrane rupture to form large pores, which are subsequently stabilized by peptide adsorption to the pore edges. This disruption to the membrane is presumably responsible for cell death. Amyloidal peptides also show evidence of stable large pore formation, however, the mechanism for pore stabilization appears linked with their ability to form fibrils and prefibrillar aggregates and oligomers. There is some evidence that pores and membrane defects in fact act as nucleation sites for these structures. Where possible we have related the experimental and theoretical work to our own simulation findings in an effort to produce a comprehensive, albeit speculative picture for the mechanisms of action for this important group of peptides. PMID- 26265352 TI - Research Advances in the Treatment of Melanoma by Treat Melanoma. AB - Melanoma is a highly malignant tumor. Prognoses of melanoma patients are often unsatisfactory due to poor operational and chemoradiational efficacy. Recently, researches for melanoma treatment have found multipeptide vaccines a favorite and possible breakthrough as they are stable in chemical property and easy to be synthesized, have no carcinogenecity and dispense with virus vector. Studies have shown that the immunogenicity of multipeptide vaccines could be enhanced by use of immunoadjuvants, joining dendritic cells (DCs), full-length or epitope superposited antigen peptides, costimulatory molecules and cellpenetrating peptides fusion, thereby improving anti-tumor effect. Certain achievements have been obtained in clinical treatment of melanoma by multipeptide vaccines, but problems including poor immunogenicity and human leukocyte antigen (HLA) phenotype restriction may require further study. PMID- 26265354 TI - Peptide Bacteriocins--Structure Activity Relationships. AB - With the growing concerns in the scientific and health communities over increasing levels of antibiotic resistance, antimicrobial peptide bacteriocins have emerged as promising alternatives to conventional small molecule antibiotics. A substantial attention has recently focused on the utilization of bacteriocins in food preservation and health safety. Despite the fact that a large number of bacteriocins have been reported, only a few have been fully characterized and structurally elucidated. Since knowledge of the molecular structure is a key for understanding the mechanism of action and therapeutic effects of peptide, we centered our focus in this review on the structure activity relationships of bacteriocins with a particular focus in seven bacteriocins, namely, nisin, microcin J25, microcin B17, microcin C, leucocin A, sakacin P, and pediocin PA-1. Significant structural changes responsible for the altered activity of the recent bacteriocin analogues are discussed here. PMID- 26265355 TI - Peptide modules for overcoming barriers of nucleic acids transport to cells. AB - Absence of safe and efficient methods of nucleic acids delivery is one of the major issues which limits the development of human gene therapy. Highly efficient viral vectors raise questions due to safety reasons. Among non-viral vectors peptide-based carriers can be considered as good candidates for the development of "artificial viruses"--multifunctional polyplexes that mimic viruses. Suggested strategy to obtain multifunctionality is to combine several peptide modules into one modular carrier. Different kinds of peptide modules are needed for successful overcoming barriers of nucleic acids transport into the cells. Design of such modules and establishment of structure-function relationships are issues of importance to researchers working in the field of nucleic acids delivery. PMID- 26265356 TI - Early and recent psychosocial stress and telomere length in older adults. AB - BACKGROUND: Psychosocial stress has been associated with an increased risk for mental and somatic health problems across the life span. Some studies in younger adults linked this to accelerated cellular aging, indexed by shortened telomere length (TL). In older adults, the impact of psychosocial stress on TL may be different due to the lifetime exposure to competing causes of TL-shortening. This study aims to assess whether early and recent psychosocial stressors (childhood abuse, childhood adverse events, recent negative life events, and loneliness) were associated with TL in older adults. METHODS: Data were from the Netherlands Study of Depression in Older Persons (NESDO) in which psychosocial stressors were measured in 496 persons aged 60 and older (mean age 70.6 (SD 7.4) years) during a face-to-face interview. Leukocyte TL was determined using fasting blood samples by performing quantitative polymerase chain reaction (qPCR) and was expressed in base pairs (bp). RESULTS: Multiple regression analyses, adjusted for age, sex, and chronic diseases, showed that childhood abuse, recent negative life events and loneliness were unrelated to TL. Only having experienced any childhood adverse event was weakly but significantly negatively associated with TL. CONCLUSIONS: Our findings did not consistently confirm our hypothesis that psychosocial stress is associated with shorter TL in older adults. Healthy survivorship or other TL-damaging factors such as somatic health problems seem to dominate a potential effect of psychosocial stress on TL in older adults. PMID- 26265357 TI - Combination of Universal Mechanical Testing Machine with Atomic Force Microscope for Materials Research. AB - Surface deformation and fracture processes of materials under external force are important for understanding and developing materials. Here, a combined horizontal universal mechanical testing machine (HUMTM)-atomic force microscope (AFM) system is developed by modifying UMTM to combine with AFM and designing a height adjustable stabilizing apparatus. Then the combined HUMTM-AFM system is evaluated. Finally, as initial demonstrations, it is applied to analyze the relationship among macroscopic mechanical properties, surface nanomorphological changes under external force, and fracture processes of two kinds of representative large scale thin film materials: polymer material with high strain rate (Parafilm) and metal material with low strain rate (aluminum foil). All the results demonstrate the combined HUMTM-AFM system overcomes several disadvantages of current AFM-combined tensile/compression devices including small load force, incapability for large scale specimens, disability for materials with high strain rate, and etc. Therefore, the combined HUMTM-AFM system is a promising tool for materials research in the future. PMID- 26265358 TI - Simulations of thermodynamics and kinetics on rough energy landscapes with milestoning. AB - We investigated by computational means the kinetics and stationary behavior of stochastic dynamics on an ensemble of rough two-dimensional energy landscapes. There are no obvious separations of temporal scales in these systems, which constitute a simple model for the behavior of glasses and some biomaterials. Even though there are significant computational challenges present in these systems due to the large number of metastable states, the Milestoning method is able to compute their kinetic and thermodynamic properties exactly. We observe two clearly distinguished regimes in the overall kinetics: one in which diffusive behavior dominates and another that follows an Arrhenius law (despite the absence of a dominant barrier). We compare our results with those obtained with an exactly-solvable one-dimensional model, and with the results from the rough one dimensional energy model introduced by Zwanzig. (c) 2015 Wiley Periodicals, Inc. PMID- 26265359 TI - Cinacalcet and Clinical Outcomes in Dialysis. AB - Secondary hyperparathyroidism (SHPT) is a common complication of end-stage renal disease and is one of the most prominent causes of a markedly increased risk of death and cardiovascular disease in this patient population. Cinacalcet hydrochloride is a new option for the treatment of SHPT, and the efficacy and effectiveness to lower parathyroid hormone levels and to improve control of mineral metabolism, even in patients with severe disease, has been well established in many clinical trials and observational studies. Currently, the focus has moved to the impact of cinacalcet on hard clinical outcomes, and two randomized controlled trials, ADVANCE and EVOLVE, have been performed to assess the effects of cinacalcet on cardiovascular calcification and the risk of cardiovascular events and mortality, respectively. Although the primary analysis of both trials did not find significant effects of cinacalcet, the benefit of cinacalcet was suggested in the subanalyses in which the potential problems of the trials were taken into account. These positive results are consistent with experimental studies showing favorable effects of cinacalcet on bone metabolism and vascular calcification, providing plausibility to support the beneficial effects of cinacalcet. Definitive evidence is, however, still lacking, and further efforts should be made to establish the optimal role of cinacalcet in the treatment of SHPT. PMID- 26265361 TI - Authors' reply to Steele and colleagues. PMID- 26265360 TI - Antifungal activity of Brevibacillus laterosporus JX-5 and characterization of its antifungal components. AB - The establishment of safe and effective methods for controlling fungal disease is an urgent issue in agriculture and forestry. Microbiological control of plant disease is expected to achieve better results than use of chemically derived fungicides. This study aimed to establish Brevibacillus laterosporus JX-5 as a potential microbiological control agent of poplar canker. The bacterium was isolated from the poplar rhizosphere and demonstrated significant growth inhibition of several pathogenic fungi in vitro. The antifungal components of Br. laterosporus JX-5 were isolated and identified. The fermentation broth of Br. laterosporus JX-5 and its main antifungal component, designated as component B, reduced Botryosphaeria dothidea associated canker of the excised poplar branch by 70 and 90%, respectively. Component B is considerably heat-stable, adaptable to a broad pH range, and UV-resistant. It could inhibit Bo. dothidea by permeating the fungal membrane, fracturing the nuclei, damaging the cell wall, and eventually killing the pathogenic fungus. The antifungal activity exhibited by Br. laterosporus JX-5 and its bioactive metabolic products indicate its feasibility as a potential biocontrol agent for plant diseases. PMID- 26265362 TI - Effect of country-of-origin contextual factors and length of stay on immigrants' substance use in Spain. AB - BACKGROUND: Factors explaining disparities in risk of substance use between immigrants and natives and between immigrant subgroups are poorly understood. We aimed to describe such disparities and identify some explanatory factors in Spain. METHODS: Participants were residents aged 15-64 years from 2005 to 07 nationally representative surveys. Outcomes were prevalences of alcohol, tobacco, sedative-hypnotics, cannabis and other illegal substance use. Immigrants were recent if <5 years of Spanish stay and long term if >=10 years. Country-of-origin income per capita and population level of substance use were taken from international databases. Adjusted prevalence ratios (aPRs) and percent change from Poisson regression with robust variance were used to estimate risk disparities and effects of immigration variables. RESULTS: Most immigrants had lower substance use than natives, although it generally increased with increasing Spanish stay, especially for illegal substances. This lower risk could be partially explained by country-of-origin contextual factors as a lower level of income or substance use and religious or cultural factors such as Islam. By origin, recent immigrant aPRs and convergence-divergence risk patterns were, respectively, as follows: lower aPRs with upward convergence (often incomplete) toward natives' risk in immigrants from Muslim area, Eastern-Europe and Latin America excluding South-Cone, lower/similar aPRs with upward overtaking or divergent patterns in South-Cone Americans and similar/higher aPRs with stable or upward divergent patterns in Non-Eastern-Europeans. CONCLUSION: Spain is a host context that seems to facilitate increased substance use among immigrants, even those from countries with prevalences close to Spain. However, country-of-origin context is important in explaining disparities in substance use among immigrants. PMID- 26265363 TI - Association between second-hand smoking and acute coronary heart disease among Arab women with multiple risk factors. AB - BACKGROUND: Active smoking is a well-established risk factor for coronary heart disease (CHD). However, the role of second-hand smoking (SHS) needs further investigation. We aimed to study the association between SHS and CHD in Arab women in Israel. METHODS: A matched case-control study among non-smoking Arab women. The case group included women discharged from hospital after having acute coronary event. The control group was women without CHD who were individually matched for age and type-2 diabetes. The women were interviewed with structured questionnaires on exposure to SHS and on attitudes towards such exposure, and underwent anthropometric measurements. RESULTS: A total of 146 women were included, the majority had type-2 diabetes (68.5%) and were overweight or obese (89.4% of cases and 93.2% of controls, P = 0.727). The prevalence of exposure to domestic-SHS after marriage was higher among the cases than controls (91.8% vs. 53.4%, P < 0.001). After adjustment for hypertension, body mass index > 25 and family history, exposure to domestic-SHS after marriage was an independent risk factor for CHD (OR = 6.1, 95% CI 1.93-19.3). Compared with no exposure, the exposed for 2-6 h a day had an OR of 5.68 (1.48-21.73), and for >6 h a day the OR reached 26.12 (4.26-159.92). Women with CHD felt less comfortable voicing their concern about smoking near them and more highly agreed with prohibition of smoking. CONCLUSIONS: Exposure to domestic-SHS is independently associated with CHD in Arab women, with a strong dose-response relationship, emphasizing the need for public health initiatives to reduce exposure to domestic-SHS. PMID- 26265364 TI - Will the trilogue on the EU Data Protection Regulation recognise the importance of health research? PMID- 26265366 TI - Breast Cancer Management Updates: Young and Older, Pregnant, or Male. AB - Every year, more and more patients fall into rare or extreme categories of breast cancer-young, elderly, pregnant, or male. Contributing factors may be improved risk assessment and screening techniques (especially of dense breast tissue), delayed childbearing, and the aging population. These patients can challenge usual medical decision making because of their unique situation. There might be a concern for the fetus, worry about future fertility, a question of local control in a man, or concern for overdiagnosis or overtreatment in an older patient. Because these populations are seldom included in the large breast cancer trials from which standard treatment recommendations are made, an update on management for young, elderly, pregnant, and male breast cancer patients may be helpful. PMID- 26265365 TI - Breast-Conserving Surgery in Bilateral Breast Cancer. AB - BACKGROUND: Bilateral breast cancer (BBC) may present as synchronous (SBC) or metachronous breast cancer (MBC). Optimal surgical management of BBC patients is not well-defined. In this study, we report on histopathology, treatment, and outcomes in BBC patients. METHODS: Upon Institutional Review Board approval, we identified BBC patients diagnosed and treated for invasive breast cancer between 1999 and 2007. Retrospective chart review for demographics, histopathology, treatment, and outcomes was performed, and factors associated with BCS choice were collected. Contraindication to BCS was defined as any of the following one breast findings: multicentric disease, tumor considered too large for BCS, and a patient without a nominal breast size for acceptable cosmetic results. McNemar's test for matched pairs (binary variables) or the paired t test (continuous variables) were used to examine if a pathologic characteristic differed within a cancer pair. Kaplan-Meier methods estimated overall survival (OS). RESULTS: A total of 203 BBC patients (119 SBC, 84 MBC) comprised our study group. Histopathologic characteristics of the first and second cancers diagnosed in both the SBC and MBC patients were very similar in histologic type and molecular profiles. Overall, 57% of MBC patients underwent breast-conserving surgery (BCS) at initial diagnosis versus 34% of patients with SBC. BCS contraindications were similar in both groups: 16 (34%) MBC patients and 28 (36%) SBC patients. Kaplan Meier OS estimates at 5 and 10 years were 86 and 78% for MBC, and 87 and 77% for SBC patients, respectively. CONCLUSIONS: OS was excellent for both the MBC and SBC groups. Contraindications to BCS did not differ between groups. However, patients with SBC were less likely to undergo BCS compared with patients with MBC at the time of initial diagnosis. PMID- 26265367 TI - Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC): The Need for Accessible Data in Real Time. PMID- 26265368 TI - A Minimally Invasive Technique to Obtain Optimal Tumor Margins in Anatomically Confined Locations Using a Contoured Stapler. PMID- 26265369 TI - Injectable cryogel-based whole-cell cancer vaccines. AB - A biomaterial-based vaccination system that uses minimal extracorporeal manipulation could provide in situ enhancement of dendritic cell (DC) numbers, a physical space where DCs interface with transplanted tumour cells, and an immunogenic context. Here we encapsulate GM-CSF, serving as a DC enhancement factor, and CpG ODN, serving as a DC activating factor, into sponge-like macroporous cryogels. These cryogels are injected subcutaneously into mice to localize transplanted tumour cells and deliver immunomodulatory factors in a controlled spatio-temporal manner. These vaccines elicit local infiltrates composed of conventional and plasmacytoid DCs, with the subsequent induction of potent, durable and specific anti-tumour T-cell responses in a melanoma model. These cryogels can be delivered in a minimally invasive manner, bypass the need for genetic modification of transplanted cancer cells and provide sustained release of immunomodulators. Altogether, these findings indicate the potential for cryogels to serve as a platform for cancer cell vaccinations. PMID- 26265370 TI - Loss of hippocampal function impairs pattern separation on a mouse touch-screen operant paradigm. AB - The hippocampus is heavily involved in the learning and memory processes necessary to successfully encode environmental stimuli and representations over time. Impairment of hippocampal function is associated with numerous neuropsychiatric diseases and can lead to detriments in the quality of life. In order to take full advantage of preclinical models of these disorders, there is a need for the development of more refined measures of clinically relevant hippocampal behaviors. While arena-based navigation tasks have provided fundamental information regarding the role of the hippocampus in spatial memory, the development of automated operant variants have had mixed results. Recently, an automated touch-screen paradigm has been shown to be highly sensitive to hippocampal function in the rat and eliminated mediating strategies that arose in previous tasks. Here we show that mice with lesions encompassing the entire ventral portion of the dorsal hippocampus are impaired on pattern separation behavior using a delayed nonmatching-to-location (TUNL) adapted for mice. Lesioned mice readily acquired the task at control rates when separations were maximal and delay periods were short while decreasing separations significantly impaired lesion mice. However, in contrast to previously reported results in the rat, consistently increasing delays did not significantly impair performance in the lesion group. Presentation of a variable delay within a session significantly impaired performance in lesion mice across delay periods. The current results demonstrate the utility of a touch-screen paradigm for measuring hippocampal dependent pattern separation in the mouse and establish the paradigm as an important platform for future studies in disease models. PMID- 26265371 TI - Prognosis of spontaneous cervical artery dissection and transcranial Doppler findings associated with clinical outcomes. AB - OBJECTIVES: We categorised spontaneous cervical artery dissection (sCAD) by radiological features and investigated factors associated with favourable outcomes. METHODS: We retrospectively analysed 128 patients with sCAD with a median follow-up duration of 25 months. Twenty-nine constituted the aneurysm group, 52 the stenotic group, and 47 the occlusive group. Various relevant factors, including National Institute of Health Stroke Scale (NIHSS) scores, type of antithrombotic therapy, stroke progression in the first week, and transcranial Doppler (TCD) flow-waveforms (in the occlusive subgroup) were analysed. Favourable outcomes were defined as a 1-year modified Rankin-Scale score of 0-1. Favourable anatomical outcomes were defined as a reversal of dissection associated stenosis during follow-up. RESULTS: The aneurysm and stenotic groups showed favourable outcomes, while the occlusive group outcomes were less favourable. In the stenotic group, anticoagulation, an NIHSS score >=4, and stroke progression were inversely associated with favourable long-term outcomes. Remarkably, in the occlusive group, flow abnormality more severe than minimal flow was associated with stroke progression, unfavourable long-term outcome, and arterial irreversibility. CONCLUSIONS: The outcome of sCAD depends on its radiological subtype. In the occlusive subtype, which is associated with the worst outcome, TCD flow analysis may predict acute stroke progression and long term outcome. KEY POINTS: * Outcomes in cervical artery dissection may be determined by radiological subtypes. * The aneurysm and stenotic groups had favourable outcomes. * The occlusive group had less favourable functional outcomes. * Flow-waveform analysis by TCD could predict functional and anatomical outcomes. PMID- 26265372 TI - Do labetalol and methyldopa have different effects on pregnancy outcome? Analysis of data from the Control of Hypertension In Pregnancy Study (CHIPS) trial. AB - OBJECTIVE: To compare pregnancy outcomes, accounting for allocated group, between methyldopa-treated and labetalol-treated women in the CHIPS Trial (ISRCTN 71416914) of 'less tight' versus 'tight' control of pregnancy hypertension. DESIGN: Secondary analysis of CHIPS Trial cohort. SETTING: International randomised controlled trial (94 sites, 15 countries). POPULATION OR SAMPLE: Of 987 CHIPS recruits, 481/566 (85.0%) women treated with antihypertensive therapy at randomisation. Of 981 (99.4%) women followed to delivery, 656/745 (88.1%) treated postrandomisation. METHODS: Logistic regression to compare outcomes among women who took methyldopa or labetalol, adjusted for the influence of baseline factors. MAIN OUTCOME MEASURES: CHIPS primary (perinatal loss or high level neonatal care for >48 hours) and secondary (serious maternal complications) outcomes, birthweight <10th centile, severe maternal hypertension, pre-eclampsia and delivery at <34 or <37 weeks. RESULTS: Methyldopa and labetalol were used commonly at randomisation (243/987, 24.6% and 238/987, 24.6%, respectively) and post-randomisation (224/981, 22.8% and 433/981, 44.1%, respectively). Following adjusted analyses, methyldopa (versus labetalol) at randomisation was associated with fewer babies with birthweight <10th centile [adjusted odds ratio (aOR) 0.48; 95% CI 0.20-0.87]. Methyldopa (versus labetalol) postrandomisation was associated with fewer CHIPS primary outcomes (aOR 0.64; 95% CI 0.40-1.00), birthweight <10th centile (aOR 0.54; 95% CI 0.32-0.92), severe hypertension (aOR 0.51; 95% CI 0.31 0.83), pre-eclampsia (aOR 0.55; 95% CI 0.36-0.85), and delivery at <34 weeks (aOR 0.53; 95% CI 0.29-0.96) or <37 weeks (aOR 0.55; 95% CI 0.35-0.85). CONCLUSION: These nonrandomised comparisons are subject to residual confounding, but women treated with methyldopa (versus labetalol), particularly those with pre-existing hypertension, may have had better outcomes. TWEETABLE ABSTRACT: There was no evidence that women treated with methyldopa versus labetalol had worse outcomes. PMID- 26265373 TI - Gamma-delta T-cell lymphoma arising in a long-standing cutaneous plaque. AB - The precise classification and characterization of primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) has been hindered by clinical and morphologic features that overlap with other lymphomas, especially subcutaneous panniculitis-like T cell lymphoma (SPTCL). The recent World Health Organization/European Organization for Research and Treatment of Cancer (WHO/EORTC) classification distinguishes the more aggressive PCGD-TCL from the usually indolent SPTCL, however. We report a 30 year-old woman with an indurated violaceous plaque on the left cheek that had been present for several years. Biopsies showed a dense lymphocytic infiltrate involving the subcutis and dermis that consisted mostly of small and medium-sized lymphocytes, some with irregular nuclear contours and dense chromatin. These cells were positive for TIA-1, TCR-gamma and CD8, but negative for beta-F1 and granzyme-B. Staging with positron emission tomography-computed tomography (PET/CT), CBC and bone marrow with flow cytometry identified lymphadenopathy as well as blood and marrow involvement by an abnormal TCRgd-positive T-cell proliferation (Ann Arbor Stage IV). The patient's history of a long-standing lesion in this case is unusual, in that gamma-delta T-cell lymphomas are typically rapidly progressive neoplasms. As such, it raises the possibility of 'transformation' of a long-standing inflammatory process into an overt lymphoma. PMID- 26265374 TI - T-cell immunoglobulin mucin-3 expression in bladder urothelial carcinoma: Clinicopathologic correlations and association with survival. AB - BACKGROUND: T cell immunoglobulin mucin-3 (Tim-3) was initially recognized as a pivotal immune checkpoint inhibitor that maintains immune homeostasis and tolerance. Recently, Tim-3 has been demonstrated to play an important role in tumor-associated immune suppression and aberrant Tim-3 expression has been reported in several human malignancies. However, the role of Tim-3 in bladder urothelial carcinoma (BUC) remains largely unknown. The present study aims to investigate Tim-3 expression in BUC and analyze correlations with clinicopathologic outcomes and postoperative survival. METHODS: Tim-3 protein expressions were detected in paraffin embedded sections from 100 patients with BUC by immunohistochemistry. Expressions were correlated with clinicopathologic outcomes and postoperative survival. RESULTS: Tim-3 protein was over-expressed in bladder cancer cells, tumor infiltrating lymphocytes and endothelial cells from patients with BUC. The expression levels of Tim-3 were significantly correlated with advanced pathological grade and T stage. Moreover, another immune checkpoint molecule programmed death receptor-1(PD-1) was also over- expressed in BUC tissues and had a significant correlation with Tim-3. Multivariate analysis showed that Tim-3 expression, as well as PD-1 expression was both independent predictors of disease-free survival and overall survival in patients with BUC. CONCLUSION: Tim-3 over-expression implies adverse clinical outcomes for BUC, which suggests it is a potential prognostic biomarker and a novel therapeutic target in BUC. PMID- 26265375 TI - Commissioning for menopause specialist services: A local perspective: An internet based survey to assess the potential demand for menopause care in West Cheshire and the skills of local primary care clinicians in this field, with a view to informing future commissioning locally. AB - OBJECTIVE: This study explores the perceived volume of women affected by peri- or post-menopausal issues that present to primary care clinicians in West Cheshire, plus the self-reported confidence of those clinicians in managing the menopause, and whether or not they feel that they and their patients should have access to a specialist menopause service. STUDY DESIGN: Completion of an electronic survey. POPULATION: General practitioners and practice nurses working in West Cheshire. MAIN OUTCOME MEASURE: To provide evidence for future local commissioning of menopause services. RESULTS: Ninety-one clinicians working within West Cheshire were sent an email request to complete the survey with 53 responses received (58%). The majority were general practitioners and were within the 35-54 year age range. The majority perceived that, each week in their clinical practice, they see between one and eight women who are affected by peri- or post-menopausal symptoms. Regarding their self-reported skills and knowledge in managing the menopause, almost half felt they had 'good' knowledge but 'recognised (they) had learning needs'. Seven of the 53 (13%) felt their skills were 'not good'. Two thirds of those clinicians who completed the survey felt that they and their patients should have access to a specialist menopause service locally. CONCLUSIONS: In the area covered by West Cheshire clinical commissioning group, there is no currently commissioned menopause service. This study has demonstrated that a substantial number of women present each week to clinicians working in this area who are felt to have peri- or post-menopausal symptoms. The clinicians have self-reported learning needs. Qualitative data from the survey would suggest training can be difficult to access. There is a clear need, both ethically and medically, for the commissioning of a West Cheshire specialist menopause service, with the proposed model being an integrated and holistic care model. Menopause care, and post-reproductive healthcare generally, provides an opportunity for collaboration and partnership working within an outcomes-based commissioning model. This study could be reviewed and replicated in other areas for comparison. PMID- 26265376 TI - Recent progress in gene therapy to deliver nucleic acids with multivalent cationic vectors. AB - Due to the potential use as transfecting agents of nucleic acids (DNA or RNA), multivalent cationic non-viral vectors have received special attention in the last decade. Much effort has been addressed to synthesize more efficient and biocompatible gene vectors able to transport nucleic acids into the cells without provoking an immune response. Among them, the mostly explored to compact and transfect nucleic acids are: (a) gemini and multivalent cationic lipids, mixed with a helper lipid, by forming lipoplexes; and (b) cationic polymers, polycations, and polyrotaxanes, by forming polyplexes. This review is focused on the progress and recent advances experimented in this area, mainly during the present decade, devoting special attention to the lipoplexes and polyplexes, as follows: (a) to its biophysical characterization (mainly electrostatics, structure, size and morphology) using a wide variety of experimental methods; and (b) to its biological activity (transfection efficacy and cytotoxicity) addressed to confirm the optimum formulations and viability of these complexes as very promising gene vectors of nucleic acids in nanomedicine. PMID- 26265377 TI - Dermatoglyphics in hypertension: a review. AB - Hypertension is a major contributor to the global burden of disease and mortality. A major medical advancement would be a better means to ascertain which persons are at higher risk for becoming hypertensive beforehand. To that end, there have been a number of studies showing that certain dermatoglyphic markers are associated with hypertension. This association could be explained if the risk toward developing hypertension later on in life is somehow connected with fetal development of dermatoglyphics. It would be highly valuable from a clinical standpoint if this conjecture could be substantiated since dermatoglyphic markers could then be used for screening out individuals who might be at an elevated risk of becoming hypertensive. The aim of this review was to search for and appraise available studies that pertain to the association between hypertension and dermatoglyphics.A systematic literature search conducted using articles from MEDLINE (PubMed), Trip, Cochran, Google scholar, and gray literature until December 2014. Of the 37 relevant publications, 17 were included in the review. The review performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement.This review showed a fairly consistent finding of an increased frequency of whorl patterns along with a higher mean total ridge count in digital dermatoglyphic results in hypertensive samples compared to controls. However, it was imperative to discuss several limitations found in the studies that could make this association as yet unsettled. PMID- 26265378 TI - ALOMYbase, a resource to investigate non-target-site-based resistance to herbicides inhibiting acetolactate-synthase (ALS) in the major grass weed Alopecurus myosuroides (black-grass). AB - BACKGROUND: Herbicide resistance in agrestal weeds is a global problem threatening food security. Non-target-site resistance (NTSR) endowed by mechanisms neutralising the herbicide or compensating for its action is considered the most agronomically noxious type of resistance. Contrary to target site resistance, NTSR mechanisms are far from being fully elucidated. A part of weed response to herbicide stress, NTSR is considered to be largely driven by gene regulation. Our purpose was to establish a transcriptome resource allowing investigation of the transcriptomic bases of NTSR in the major grass weed Alopecurus myosuroides L. (Poaceae) for which almost no genomic or transcriptomic data was available. RESULTS: RNA-Seq was performed from plants in one F2 population that were sensitive or expressing NTSR to herbicides inhibiting acetolactate-synthase. Cloned plants were sampled over seven time-points ranging from before until 73 h after herbicide application. Assembly of over 159M high quality Illumina reads generated a transcriptomic resource (ALOMYbase) containing 65,558 potentially active contigs (N50 = 1240 nucleotides) predicted to encode 32,138 peptides with 74% GO annotation, of which 2017 were assigned to protein families presumably involved in NTSR. Comparison with the fully sequenced grass genomes indicated good coverage and correct representation of A. myosuroides transcriptome in ALOMYbase. The part of the herbicide transcriptomic response common to the resistant and the sensitive plants was consistent with the expected effects of acetolactate-synthase inhibition, with striking similarities observed with published Arabidopsis thaliana data. A. myosuroides plants with NTSR were first affected by herbicide action like sensitive plants, but ultimately overcame it. Analysis of differences in transcriptomic herbicide response between resistant and sensitive plants did not allow identification of processes directly explaining NTSR. Five contigs associated to NTSR in the F2 population studied were tentatively identified. They were predicted to encode three cytochromes P450 (CYP71A, CYP71B and CYP81D), one peroxidase and one disease resistance protein. CONCLUSIONS: Our data confirmed that gene regulation is at the root of herbicide response and of NTSR. ALOMYbase proved to be a relevant resource to support NTSR transcriptomic studies, and constitutes a valuable tool for future research aiming at elucidating gene regulations involved in NTSR in A. myosuroides. PMID- 26265379 TI - Association Study of IL-4 -590 C/T and DDX39B -22 G/C Polymorphisms with the Risk of Late-Onset Alzheimer's Disease in Iranian Population. AB - Interleukin-4 (IL-4), an important anti-inflammatory cytokine, is elucidated to regulate amyloid beta-induced production of the inflammatory cytokines such as IL 1 and IL-6. It is assumed that IL-4 may involve in the inflammation pathology of surrounding senile plaques in Alzheimer's disease (AD) patients. DEAD (Asp-Glu Ala-Asp) box polypeptide 39B (DDX39B), appears to be involved in regulation of the inflammatory cytokines which are in correlation with AD pathology. This study was conducted to investigate the two single nucleotide polymorphisms (SNPs), IL-4 -590 C/T and DDX39B -22 G/C, association with the risk of late-onset AD (LOAD) in Iranian population. In the present study, therefore, a cohort of 153 LOAD cases and 153 age-matched unrelated, non-dementia control subjects were analyzed for the two polymorphisms by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). Our results successfully demonstrate a protective association between the IL-4 -590 T allele, IL-4 -590 C/T heterozygous genotype (P= 0.01, OR= 0.53 and P= 0.041; OR= 0.56, respectively) and LOAD in Iranian population. A resemblance significant association was detected in female population when subjects were stratified by sex: the IL-4 -590 T allele (P= 0.02, OR= 0, 40) and the heterozygous genotype (P= 0.009, OR= 0.29). However, no significant association was observed between the DDX39B -22 G/C polymorphism in the cases and controls. Furthermore, it is clarified that the protective effect of IL-4 -590 is independent from APOE protective genotypes. Accordingly, the IL-4 -590 T allele may be applied as a protective marker in the development of LOAD in Iranian population. PMID- 26265380 TI - Regulation of carotid body oxygen sensing by hypoxia-inducible factors. AB - Oxygen (O2) sensing by the carotid body and its chemosensory reflex is critical for homeostatic regulation of breathing and blood pressure. Carotid body responses to hypoxia are not uniform but instead exhibit remarkable inter individual variations. The molecular mechanisms underlying variations in carotid body O2 sensing are not known. Hypoxia-inducible factor-1 (HIF-1) and HIF-2 mediate transcriptional responses to hypoxia. This article reviews the emerging evidence that proper expression of the HIF-alpha isoforms is a key molecular determinant for carotid body O2 sensing. HIF-1alpha deficiency leads to a blunted carotid body hypoxic response, which is due to increased abundance of HIF-2alpha, elevated anti-oxidant enzyme activity, and a reduced intracellular redox state. Conversely, HIF-2alpha deficiency results in augmented carotid body sensitivity to hypoxia, which is due to increased abundance of HIF-1alpha, elevated pro oxidant enzyme activity, and an oxidized intracellular redox state. Double heterozygous mice with equally reduced HIF-1alpha and HIF-2alpha showed no abnormality in redox state or carotid body O2 sensing. Thus, mutual antagonism between HIF-alpha isoforms determines the redox state and thereby establishes the set point for hypoxic sensing by the carotid body. PMID- 26265381 TI - Cavbeta2 transcription start site variants modulate calcium handling in newborn rat cardiomyocytes. AB - In the heart, the main pathway for calcium influx is mediated by L-type calcium channels, a multi-subunit complex composed of the pore-forming subunit CaV1.2 and the auxiliary subunits CaValpha2delta1 and CaVbeta2. To date, five distinct CaVbeta2 transcriptional start site (TSS) variants (CaVbeta2a-e) varying only in the composition and length of the N-terminal domain have been described, each of them granting distinct biophysical properties to the L-type current. However, the physiological role of these variants in Ca(2+) handling in the native tissue has not been explored. Our results show that four of these variants are present in neonatal rat cardiomyocytes. The contribution of those CaVbeta2 TSS variants on endogenous L-type current and Ca(2+) handling was explored by adenoviral-mediated overexpression of each CaVbeta2 variant in cultured newborn rat cardiomyocytes. As expected, all CaVbeta2 TSS variants increased L-type current density and produced distinctive changes on L-type calcium channel (LTCC) current activation and inactivation kinetics. The characteristics of the induced calcium transients were dependent on the TSS variant overexpressed. Moreover, the amplitude of the calcium transients varied depending on the subunit involved, being higher in cardiomyocytes transduced with CaVbeta2a and smaller in CaVbeta2d. Interestingly, the contribution of Ca(2+) influx and Ca(2+) release on total calcium transients, as well as the sarcoplasmic calcium content, was found to be TSS-variant dependent. Remarkably, determination of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) messenger RNA (mRNA) abundance and cell size change indicates that CaVbeta2 TSS variants modulate the cardiomyocyte hypertrophic state. In summary, we demonstrate that expression of individual CaVbeta2 TSS variants regulates calcium handling in cardiomyocytes and, consequently, has significant repercussion in the development of hypertrophy. PMID- 26265382 TI - Identification of proteins in hyperglycemia and stroke animal models. AB - BACKGROUND: Stroke is a major cause of disability and death in adults. Diabetes mellitus is a metabolic disorder that strongly increases the risk of severe vascular diseases. This study compared changes in proteins of the cerebral cortex during ischemic brain injury between nondiabetic and diabetic animals. METHODS: Adult male rats were injected with streptozotocin (40 mg/kg) via the intraperitoneal route to induce diabetes and underwent surgical middle cerebral artery occlusion (MCAO) 4 wk after streptozotocin treatment. Cerebral cortex tissues were collected 24 h after MCAO and cerebral cortex proteins were analyzed by two-dimensional gel electrophoresis and mass spectrometry. RESULTS: Several proteins were identified as differentially expressed between nondiabetic and diabetic animals. Among the identified proteins, we focused on the following metabolism-related enzymes: isocitrate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, adenosylhomocysteinase, pyruvate kinase, and glucose-6-phosphate isomerase (neuroleukin). Expression of these proteins was decreased in animals that underwent MCAO. Moreover, protein expression was reduced to a greater extent in diabetic animals than in nondiabetic animals. Reverse transcription-polymerase chain reaction analysis confirmed that the diabetic condition exacerbates the decrease in expression of metabolism-related proteins after MCAO. CONCLUSIONS: These results suggest that the diabetic condition may exacerbate brain damage during focal cerebral ischemia through the downregulation of metabolism-related proteins. PMID- 26265383 TI - Do patient safety indicators explain increased weekend mortality? AB - BACKGROUND: We sought to determine the differential role of patient safety indicator (PSI) events on mortality after weekend as compared with weekday admission. MATERIALS AND METHODS: We evaluated Agency for Healthcare Research and Quality PSI events within a cohort of patients with nonelective admissions. First, we identified all patients with a PSI based on day of admission (weekend versus weekday). Then, we evaluated the outcome of mortality after each PSI event. Finally, we entered age, sex, race, median household income, payer information, and Charlson comorbidity scores in regression models to develop risk ratios of weekend to weekday PSI events and mortality. RESULTS: There were 28,236,749 patients evaluated with 428,685 (1.5%) experiencing one or more PSI events. The rate of PSI was the same for patients admitted on weekends as compared to weekdays (1.5%). However, the risk of mortality was 7% higher if a PSI event occurred to a patient admitted on a weekend as compared with a weekday. In addition, compared to patients admitted on weekdays, patients admitted on weekends had a 36% higher risk of postoperative wound dehiscence, 19% greater risk of death in a low-mortality diagnostic-related group, 19% increased risk of postoperative hip fracture, and 8% elevated risk of surgical inpatient death. CONCLUSIONS: Risk adjusted data reveal that PSI events are substantially higher among patients admitted on weekends. The considerable differences in death after PSI events in patients admitted on weekends as compared with weekdays indicate that responses to adverse events may be less effective on weekends. PMID- 26265384 TI - 'They wrote "gay" on her file': transgender Ugandans in HIV prevention and treatment. AB - This paper examines the ways in which HIV-related programmes for heterosexual Ugandans and also for men who have sex with men work to deny healthcare services to transgender people in Uganda. Contrary to current conventional wisdom, the study found that the widespread use of the term 'men who have sex with men' produces greater barriers to healthcare for queer Ugandans than identity categories such as 'lesbian' or 'transgender'. Interventions for men who have sex with men assume a male-identified sexual subject with agency over sexual practices, such as frequency of condom use. Based on two years of ethnographic research in Kampala, I suggest that the focus on individual sexual practices harms transgender people in two ways. First, current HIV prevention and treatment programmes fail to account for risk factors that accrue to both male and female transgender Ugandans due to the social enforcement of gender norms. Second, the term men who have sex with men directs attention towards stigmatised sexual practices, producing the neglect and abuse of non-heteronormative individuals. In the context of Ugandan healthcare, terms such as 'transgender' and kuchu instead focus attention on the dignity and humanity of the rights-bearing person. These findings emphasise how health practitioners must pay attention to emic categories in order to address the ways in which vulnerability is distributed along social vectors of difference. PMID- 26265385 TI - Future therapy for hepatitis B virus infection. AB - We can now control hepatitis B virus infection by continuously administering nucleoside and nucleotide analogues such as entecavir and tenofovir. These drugs are generally safe and sufficiently effective, but future drugs are needed that can show off-treatment efficacy--in other words, eradication of latent hepatitis B virus DNA (covalently closed circular DNA) in the hepatocytes. This article is an overview of new drugs under development and some novel strategies to inhibit hepatitis B virus proliferation. PMID- 26265386 TI - Repurposing of anticancer drugs: in vitro and in vivo activities against Schistosoma mansoni. AB - BACKGROUND: Drug discovery for the neglected tropical disease schistosomiasis has a high priority. Anticancer drugs, especially protein kinase inhibitors, might serve as a starting point for drug discovery owing to the importance of protein kinases in helminth growth and development. Furthermore, the Schistosoma mansoni genome encodes several genes for targets of drugs marketed for human use, including several anticancer drugs. METHODS: In this study, we screened the approved oncology drug set of the National Cancer Institute's Developmental Therapeutic Program for antischistosomal activity. Drugs were tested in vitro against the larval and adult stage of S. mansoni. IC50 values and albumin binding were determined for active compounds. Lead compounds were tested in the chronic S. mansoni mouse model. RESULTS: Eleven of the 114 compounds tested revealed IC50 values <= 10 MUM against both S. mansoni stages. Five of these lost activity against adult S. mansoni in the presence of serum albumin. Of 6 compounds studied in vivo, the highest activity was observed from two kinase inhibitors trametinib, and vandetanib, which reduced worm burden by 63.6 and 48.1% respectively, after a single oral dose of 400 mg/kg body weight. CONCLUSION: Our study has confirmed that oncology drugs possess antischistosomal activity. There is space for further investigation, including elucidation of the mechanisms of action of schistosome active cancer drugs, application of different treatment courses, and structure activity relationship studies for improving drug potency. PMID- 26265387 TI - Exploring sources of construct-relevant multidimensionality in psychiatric measurement: A tutorial and illustration using the Composite Scale of Morningness. AB - This paper illustrates a psychometric approach of broad relevance to psychiatric research instruments. Many instruments include indicators related to more than one source of true-score variance due to the: (1) assessment of conceptually adjacent constructs; (2) the presence of a global construct underlying answers to items designed to assess multiple dimensions. Exploratory structural equation modelling (ESEM) is naturally suited to the investigation of the first source, whereas bifactor models are particularly suited to the investigation of the second source. When both sources are present, bifactor-ESEM becomes the model of choice. To illustrate this framework, we use the responses of 1159 adults [655 female, 504 male, mean age (Mage ) = 41.84] who completed the French Version of the Composite Scale of Morningness (CSM). We investigate the factor structure of the CSM, test the relations between CSM factors and body mass index, and verify the measurement invariance of the model across gender and age groups. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26265388 TI - Refinement of adsorptive coatings for fluorescent riboflavin-receptor-targeted iron oxide nanoparticles. AB - Flavin mononucleotide (FMN) is a riboflavin derivative that can be exploited to target the riboflavin transporters (RFTs) and the riboflavin carrier protein (RCP) in cells with high metabolic activity. In this study we present the synthesis of different FMN-coated ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) and their efficiency as targeting contrast agents. Since FMN alone cannot stabilize the nanoparticles, we used adenosine phosphates--AMP, ADP and ATP--as spacers to obtain colloidally stable nanoparticles. Nucleotides with di- and triphosphate groups were intended to increase the USPIO charge and thus improve zeta potential and stability. However, all nanoparticles formed negatively charged clusters with similar properties in terms of zeta potential ( 28 +/- 2 mV), relaxivity (228-259 mM(-1) s(-1) at 3 T) and hydrodynamic radius (53-85 nm). Molecules with a higher number of phosphate groups, such as ADP and ATP, have a higher adsorption affinity towards iron oxide, which, instead of providing more charge, led to partial desorption and replacement of FMN. Hence, we obtained USPIOs carrying different amounts of targeting agent, which significantly influenced the nanoparticles' uptake. The nanoparticles' uptake by different cancer cells and HUVECs was evaluated photometrically and with MR relaxometry, showing that the cellular uptake of the USPIOs increases with the FMN amount on their surface. Thus, for USPIOs targeted with riboflavin derivatives the use of spacers with increasing numbers of phosphate groups does not improve either zeta potential or the particles' stability, but rather detaches the targeting moieties from their surface, leading to lower cellular uptake. PMID- 26265389 TI - Uterine prolapse and its impact on quality of life in the Jhaukhel-Duwakot Health Demographic Surveillance Site, Bhaktapur, Nepal. AB - BACKGROUND: Uterine prolapse (UP) is a reproductive health problem and public health issue in low-income countries including Nepal. OBJECTIVE: We aimed to identify the contributing factors and stages of UP and its impact on quality of life in the Jhaukhel-Duwakot Health Demographic Surveillance Site of Bhaktapur, Nepal. DESIGN: Our three-phase study used descriptive cross-sectional analysis to assess quality of life and stages of UP and case-control analysis to identify contributing factors. First, a household survey explored the prevalence of self reported UP (Phase 1). Second, we used a standardized tool in a 5-day screening camp to determine quality of life among UP-affected women (Phase 2). Finally, a 1 month community survey traced self-reported cases from Phase 1 (Phase 3). To validate UP diagnoses, we reviewed participants' clinical records, and we used screening camp records to trace women without UP. RESULTS: Among 48 affected women in Phase 1, 32 had Stage II UP and 16 had either Stage I or Stage III UP. Compared with Stage I women (4.62%), almost all women with Stage III UP reported reduced quality of life. Decreased quality of life correlated significantly with Stages I-III. Self-reported UP prevalence (8.7%) included all treated and non treated cases. In Phase 3, 277 of 402 respondents reported being affected by UP and 125 were unaffected. The odds of having UP were threefold higher among illiterate women compared with literate women (OR=3.02, 95% CI 1.76-5.17), 50% lower among women from nuclear families compared with extended families (OR=0.56, 95% CI 0.35-0.90) and lower among women with 1-2 parity compared to >5 parity (OR=0.33, 95% CI 0.14-0.75). CONCLUSIONS: The stages of UP correlated with quality of life resulting from varied perceptions regarding physical health, emotional stress, and social limitation. Parity, education, age, and family type associated with UP. Our results suggest the importance of developing policies and programs that are focused on early health care for UP. Through family planning and health education programs targeting women, as well as women empowerment programs for prevention of UP, it will be possible to restore quality of life related to UP. PMID- 26265390 TI - Clinicopathological factors associated with HER2 status in gastric cancer: results from a prospective multicenter observational cohort study in a Japanese population (JFMC44-1101). AB - BACKGROUND: Human epidermal growth factor (HER) 2 positivity and its association with clinicopathological factors remain unclear in Japanese gastric cancer (GC) patients. We performed a prospective, multicenter, observational cohort study to evaluate HER2 protein expression and gene amplification in Japanese metastatic and recurrent GC patients, and explored its correlations with clinicopathological features. METHODS: HER2 protein expression and gene amplification were centrally assessed in formalin-fixed, paraffin-embedded GC tissue by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Patient information was collected, and associations between clinicopathological factors and HER2 positivity (IHC score 3+ and/or FISH positive) and low HER2 expression (IHC score 0/FISH positive or IHC score 1+/FISH positive) were examined. RESULTS: From September 2011 to June 2012, 1461 patients were registered across 157 sites, and the HER2 status of 1427 patients was evaluated. The rate of HER2 positivity was 21.2 %, whereas the rate of high HER2 expression (IHC score 2+/FISH positive or IHC score 3+) was 15.6 % and that of low HER2 expression was 7.0 %. Multiple logistic regression analysis identified intestinal type, absence of peritoneal metastasis, and hepatic metastasis as significant independent factors related to HER2 positivity. The intestinal type was confirmed to be the GC subtype predominantly associated with lower HER2 expression. Sampling conditions including number of biopsy samples, formalin concentration, and formalin-fixation time did not significantly affect HER2 positivity. CONCLUSIONS: HER2 expression in Japanese patients was comparable to that in other populations examined. Intestinal type was an independent factor related to HER2 positivity and low HER2 expression. PMID- 26265392 TI - An asymmetric allylic alkylation reaction of 3-alkylidene oxindoles. AB - An efficient asymmetric allylic alkylation reaction with respect to 3-alkylidene oxindoles and racemic Morita-Baylis-Hillman carbonate has been achieved by using a chiral biscinchona alkaloid catalyst, which delivers the gamma-substituted alkylideneoxindoles with a chiral tertiary center in moderate to good yields (up to 92%) and very good enantioselectivities (up to >99% ee). PMID- 26265391 TI - Epstein-Barr virus infection serves as an independent predictor of survival in patients with lymphoepithelioma-like gastric carcinoma. AB - BACKGROUND: The pathogenesis and clinicopathologic characteristics of Epstein Barr virus (EBV)-negative lymphoepithelioma-like gastric carcinoma (LELC) are still unclear. In addition, it remains controversial whether EBV infection itself affects the prognosis of LELC. METHODS: Between 1995 and 2011, 145 LELC patients (124 patients with EBV infection and 21 patients without EBV infection) underwent radical gastrectomy with D2 lymph node dissection. The clinicopathologic features and prognosis of EBV-negative LELC cases were compared with those of EBV-positive LELC cases. The median duration of follow-up after surgery was 55 months. Microsatellite instability (MSI) analysis was performed on 20 EBV-negative LELC cases. RESULTS: EBV-negative LELC accounted for 14.5 % of the total LELC cases. EBV-negative LELC was significantly associated with older age, female sex, advanced T stage, and advanced American Joint Committee on Cancer (AJCC) tumor stage compared with EBV-positive LELC. In univariate analysis, patients with EBV negative LELC had significantly shorter overall, disease-specific, and recurrence free survival than those with EBV-positive LELC. The 5-year overall survival rates were 81.0 % for patients with EBV-negative LELC and 96.2 % for patients with EBV-positive LELC. In a Cox proportional hazards model, EBV infection, age, and AJCC tumor stage were identified as independent predictors of overall survival. MSI-high, MSI-low, and microsatellite-stable tumors accounted for 25, 10, and 65 % of EBV-negative LELC cases, respectively. MSI status did not affect the prognosis of EBV-negative LELC cases. CONCLUSIONS: EBV infection serves as an independent predictor of survival in patients with LELC. EBV-negative LELC exhibited clinicopathologic features and prognosis distinct from those of EBV positive LELC. PMID- 26265393 TI - Tiwanaku influence and social inequality: A bioarchaeological, biogeochemical, and contextual analysis of the Larache cemetery, San Pedro de Atacama, Northern Chile. AB - OBJECTIVES: To assess the relationship between the Tiwanaku polity and the individuals buried at the Middle Horizon (~AD500-1000) cemetery of Larache in northern Chile, a site that has been singled out as a potential elite foreign enclave. MATERIALS AND METHODS: We explore this association through the skeletal remains of 48 individuals interred at the cemetery of Larache using bioarchaeological, biogeochemical, and artifactual evidence. Data from cranial modification practices, violent injury, and the mortuary assemblage are used to explore culturally constructed elements of status and identity, radiogenic strontium isotope analyses provide us with a perspective on the geographic origins of these individuals, and stable carbon and nitrogen analyses allow discussion of paleodiet and access to resources. RESULTS: Radiogenic strontium isotope values show the presence of multiple first generation migrants at Larache. Stable carbon and nitrogen isotope data reveal significant differences among individuals. The mortuary context reveals a standard pattern for the oases but also includes a series of unusual burials with abundant gold and few other objects. Interestingly, both local and nonlocal individuals with different head shapes had access to the differentiated burial context; however nonlocal individuals appear to be the only ones with a heavily maize-based diet. CONCLUSIONS: Our evidence shows that Larache served as a burial place for a diverse, yet culturally integrated and potentially elite segment of the Atacameno population, but not a foreign enclave as had been postulated. PMID- 26265394 TI - Human and Tree Shrew Alpha-synuclein: Comparative cDNA Sequence and Protein Structure Analysis. AB - The synaptic protein alpha-synuclein (alpha-syn) is associated with a number of neurodegenerative diseases, and homology analyses among many species have been reported. Nevertheless, little is known about the cDNA sequence and protein structure of alpha-syn in tree shrews, and this information might contribute to our understanding of its role in both health and disease. We designed primers to the human alpha-syn cDNA sequence; then, tree shrew alpha-syn cDNA was obtained by RT-PCR and sequenced. Based on the acquired tree shrew alpha-syn cDNA sequence, both the amino acid sequence and the spatial structure of alpha-syn were predicted and analyzed. The homology analysis results showed that the tree shrew cDNA sequence matches the human cDNA sequence exactly except at nucleotide positions 45, 60, 65, 69, 93, 114, 147, 150, 157, 204, 252, 270, 284, 298, 308, and 324. Further protein sequence analysis revealed that the tree shrew alpha-syn protein sequence is 97.1 % identical to that of human alpha-syn. The secondary protein structure of tree shrew alpha-syn based on random coils and alpha-helices is the same as that of the human structure. The phosphorylation sites are highly conserved, except the site at position 103 of tree shrew alpha-syn. The predicted spatial structure of tree shrew alpha-syn is identical to that of human alpha syn. Thus, alpha-syn might have a similar function in tree shrew and in human, and tree shrew might be a potential animal model for studying the pathogenesis of alpha-synucleinopathies. PMID- 26265395 TI - Solvents Production from a Mixture of Glucose and Xylose by Mixed Fermentation of Clostridium acetobutylicum and Saccharomyces cerevisiae. AB - To overcome the xylose utilization defect in ethanol fermentation by wide-type Saccharomyces cerevisiae and alleviate the carbon catabolite repression (CCR) in acetone-butanol-ethanol (ABE) fermentation by Clostridium acetobutylicum, a novel mixed fermentation of S. cerevisiae and C. acetobutylicum was developed. When S. cerevisiae was inoculated 24 h earlier than C. acetobutylicum CH02, a higher solvents yield was achieved with 0.41 g/g, compared to 0.38 g/g in ABE fermentation, and when S. cerevisiae and C. acetobutylicum CH02 were inoculated simultaneously, a higher productivity was achieved with 0.32 g/L/h, compared to 0.15 g/L/h in ABE fermentation. The total solvents yield was improved by the high ethanol yield from glucose. The CCR in mixed fermentation was alleviated when glucose was utilized quickly by S. cerevisiae, and therefore, the productivity was improved. This study suggests that mixed fermentation is an effective solvents production method from a mixture of glucose and xylose. PMID- 26265396 TI - Fe(II)-Co(II) Double Salt Incorporated Magnetic Hydrophobic Microparticles for Invertase Adsorption. AB - Invertase (beta-fructofuranoside fructohydrolase, EC 3.2.1.26) is an enzyme widely used in the food industry. Its main function is the formation of glucose and fructose through hydrolysis of sucrose. For the separation and purification of this commercially important enzyme from aqueous solutions, magnetic poly(2 hydroxyethyl methacrylate-N-methacryloyl-L-tryptophan), m-poly(HEMA-MATrp) microparticles were developed. Magnetic properties of microparticles are provided using ferromagnetic Fe(II)-Co(II) double salt. Characterization studies of magnetic microparticles were conducted via vibrating sample magnetometer (VSM), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) analysis. Specific surface area of magnetic microparticles is 6.75 m(2)/g. Because of all experiments performed in this study, the adsorption capability of magnetic microparticles was optimized by variation of different conditions (pH, interaction time, initial invertase concentration, temperature, and ionic strength) and maximum adsorption capacity was determined as 992.64 mg invertase/g magnetic microparticles. PMID- 26265397 TI - Neuroanatomical correlates of negative emotionality-related traits: A systematic review and meta-analysis. AB - Two central traits present in the most influential models of personality characterize the response to positive and, respectively, negative emotional events. Negative emotionality (NE)-related traits are linked to vulnerability to mood and anxiety disorders; this has fuelled a special interest in examining stable differences in brain morphology associated to these traits. Structural imaging methods including voxel-based morphometry, cortical thickness analysis and diffusion tensor imaging (DTI) have yielded inconclusive and sometimes contradictory results. This review summarizes the findings reported to date through these methods and discusses them in relation to the functional imaging results. To detect topographic convergence between studies showing positive and, respectively, negative grey matter associations with NE-traits, activation likelihood estimation (ALE) meta-analyses of VBM studies were performed. Individuals scoring high on NE-related traits show consistent morphological differences in a left-lateralized circuit: higher grey matter volume (GMV) in amygdala and anterior parahippocampal gyrus and lower GMV in the orbitofrontal cortex extending into perigenual anterior cingulate cortex. Most DTI studies indicate reduced white matter integrity in various brain regions and tracts, particularly in the uncinate fasciculus and in cingulum bundle. These results show that the behavioural phenotype associated to NE traits is reflected in structural differences within the cortico-limbic system, suggesting alterations in information processing and transmission. The results are discussed from the perspective of neuron-glia interactions. Future directions are outlined based on recent developments in structural imaging techniques. PMID- 26265398 TI - Transparent and through thickness conductive polystyrene films using external magnetic fields for "Z" alignment of nickel nanoparticles. AB - A combination of transparency, electrical conductivity and flexibility is desired in the emerging flexible electronics industry for current and future applications. In this paper, we report the development of through thickness electrical conductivity in polystyrene films filled with nickel nanopowder by external magnetic field application. This process leads to the formation of nanocolumns of nickel spanning across the thickness direction while generating nanoparticle depleted regions in between. This leads to directionally dependent enhancement in optical light transmission particularly in the normal direction of the films. With the use of as little as 2 wt% (0.22 vol%) nickel we were able to achieve high through thickness conductivity under the influence of a magnetic field. While these films exhibit high through thickness conductivity they remain non-conductive in their planes as a result of the unique nanomorphology created which eliminates potential side branch formations. These films are anticipated to be used as electrodes for touch screens, electric dissipative materials for electronic packaging and other sensors. PMID- 26265399 TI - Rescuer size impact on compression velocity/duty cycle and increased survival/favorable outcome. PMID- 26265400 TI - Late diagnosis of Wellens syndrome in a patient presenting with an atypical acute coronary syndrome. PMID- 26265401 TI - Internal versus external fixation of the anterior component in unstable fractures of the pelvic ring: pooled results from a systematic review. AB - PURPOSE: Improving reduction of the pelvic ring improves long-term functional outcomes for patients. It has been demonstrated that posterior internal fixation is necessary to adequately control fractures to the posterior ring and there is evidence that supplementing this with fixation of the anterior ring improves stability. It is accepted that internal fixation provides greater stability than external fixation of the anterior ring but long-term differences in radiographic and functional outcomes have not yet been quantified. METHODS: A search of electronic databases, reference lists and review articles from 1989 to 2015 yielded 18 studies (n = 884) that met our inclusion criteria. We included studies that discussed pelvic ring injuries in adults, reported functional or radiological outcomes or complications by anterior ring intervention and exceeded 14 patients. We excluded biomechanical and cadaver studies. RESULTS: Internal fixation of the anterior pelvic ring had better functional and radiographic outcomes. Residual displacement of >10 mm was less common with internal fixation (ER 0.12, 95 % CI 0.06-0.24) than external fixation (ER 0.31, 95 % CI 0.11-0.62). Unsatisfactory outcomes also occurred at a lower rate (ER 0.09, 95 % CI 0.03 0.22) compared to external fixation (ER 0.32, 95 % CI 0.18-0.50). Losses of reduction (ER 0.02, 95 % CI 0.01-0.04 versus ER 0.07, 95 % CI 0.02-0.21), malunions (ER 0.03, 95 % CI 0.01-0.08 versus ER 0.07, 95 % CI 0.02-0.21) and delayed/non-unions (ER 0.02, 95 % CI 0.01-0.05 versus ER 0.04, 95 % CI 0.02 0.07). CONCLUSIONS: Internal fixation of the anterior pelvic ring as supplementary fixation for unstable injuries to the pelvic ring appears to result in better radiographic and functional outcomes as well as fewer complications. However, data that separated outcomes and complications in relation to interventions of the anterior pelvic ring were limited. More studies looking specifically at outcomes in relation to the type of anterior ring intervention are needed. PMID- 26265402 TI - Artificial Protection Film on Lithium Metal Anode toward Long-Cycle-Life Lithium Oxygen Batteries. AB - An artificial while very stable solid electrolyte interphase film is formed on lithium metal using an electrochemical strategy. When this protected Li anode is first used in a Li-O2 battery, the film formed on the anode can effectively suppress the parasitic reactions on the Li anode/electrolyte interface and significantly enhance the cycling stability of the Li-O2 battery. PMID- 26265403 TI - Accuracy of CT-based patient-specific guides for total knee arthroplasty in patients with post-traumatic osteoarthritis. AB - Published clinical trials who studied the accuracy of patient-specific guides (PSG) for total knee arthroplasty exclude patients with articular deformity of the knee joint. We prospectively analysed a series of 30 patients with post traumatic osteoarthritis of the knee joint with use of PSG. At 1 year post operative, the achieved biomechanical (HKA) axis and varus/valgus of the femur and tibia components were measured on anterior-posterior (AP) long-standing weight-bearing radiographs. Flexion/extension of the femoral and AP slope of the tibia component was measured on standard lateral radiographs. Percentages >3 degrees deviation of the pre-operative planned HKA axis and individual implant components were considered as outliers. Approved and used implant size, median blood loss (ml) and operation time (min) were obtained from the operation records. Pre- and 1-year post-operative patient-reported outcome measures (PROMs) were performed. Eighty-three per cent of the patients had a HKA axis restored <3 degrees of the pre-operative planned alignment. Varus/valgus outliers were 0.0 and 6.7 % for the femoral and tibial components, respectively. Percentages of outliers of flexion/extension were 36.7 % for the femoral component and 10.0 % for the AP slope of the tibial component. Median blood loss was 300 ml (50-700), while operation time was 67 min (44-144). In 20 % of all cases, the approved implant size was changed into one size smaller. One-year post-operative PROMs improved significantly. We conclude that the accuracy of CT-based PSG is not impaired in patients with post-traumatic osteoarthritis and this modality can restore biomechanical limb alignment. PMID- 26265404 TI - Periosteal desmoplastic fibroma of the tibia in a 3-year-old child. AB - Desmoplastic fibroma is a rare benign fibrogenic, locally aggressive, primary bone tumor. It is the intraosseous counterpart of soft tissue aggressive fibromatosis. The lesion may very rarely appear as a superficial bone lesion arising from the periosteum; in such cases, a soft tissue mass with changes in the adjacent bone is evident. Periosteal lesions are very rare in the literature; diagnosis is usually based on the radiographic findings, and histological proof of the tumor origin is missing. A periosteal desmoplastic fibroma of the distal tibial metaphysis in a 3-year-old boy is presented. Radiographic investigation included plain radiographs and computed tomography imaging. Both demonstrated a soft tissue lesion involving the superficial bone tissues with non-aggressive looking borders and a pressure effect with a sclerotic rim in the bone. The lesion was excised, and the surgical as well as the histological findings indicated the diagnosis of a desmoplastic fibroma of bone arising from the periosteum. No recurrence was detected 5 years after surgery. PMID- 26265405 TI - Postoperative complications in obese children undergoing adenotonsillectomy. AB - OBJECTIVE: The incidence of obesity in the pediatric population is increasing. To date, data are limited regarding safety of adenotonsillectomy in this patient population. The purpose of this study is to assess perioperative outcomes of adenotonsillectomy in the obese pediatric patient. METHODS: A review of the 2012 Kids' Inpatient Database (KID) was conducted to compare patients with clinical modification codes for adenotonsillectomy plus obesity to patients with clinical modification codes for adenotonsillectomy alone. Elements for comparison included patient demographics and concurrent discharge. An in depth review of risk factors associated with respiratory complications in obese patients was also conducted. RESULTS: A weighted total of 899 obese and 20,535 non-obese patients admitted after adenotonsillectomy were identified. When these two groups were compared, respiratory complications were found in 16.2% of obese and 9.6% of non-obese patients (p<0.0001). A diagnosis of respiratory failure or pulmonary insufficiency was statistically more common in obese patients when compared to non-obese patients (5.0% versus 3.0%, p=0.007). In obese patients, respiratory complications were associated with male gender, low income, and concomitant asthma on multivariate analysis (p=0.01, 0.004, and 0.007 respectively). CONCLUSION: Performing adenotonsillectomy on the obese pediatric patient is safe. When performing adenotonsillectomy on this patient population, one must be aware that respiratory events are the most common type of complication and risk of respiratory complications is higher in males, patients of low socioeconomic status, and patients with comorbid asthma, regardless of race or insurance status. PMID- 26265406 TI - Cell cycle: repurposing MYC and E2F in the absence of RB. PMID- 26265407 TI - Translation: competition at the ribosome exit site. PMID- 26265408 TI - Cell migration: EMT promotes contact inhibition of locomotion. PMID- 26265409 TI - Cross-sectional study of soluble selectins, fractions of circulating microparticles and their relationship to lung and skin involvement in systemic sclerosis. AB - BACKGROUND: Endothelial damage and activation may play central roles in the pathogenesis of systemic sclerosis (SSc) and are reflected by microparticles (MPs) and soluble selectins. The objective of this study was to determine if these potential biomarkers are associated with specific organ involvements or cutaneous subgroups of SSc patients. METHOD: MPs in platelet-poor plasma from 121 patients with SSc, 79 and 42 with limited and diffuse cutaneous disease, respectively, were characterized by flow cytometry for their capacity to bind annexin V in combination with surface markers of either platelets (PMPs), leukocytes (LMPs) or endothelial cells (EMPs). Soluble E- and P-selectin levels were determined in plasma. By correlation analyses, this was held against involvement of skin, lung function, lung fibrosis, pulmonary artery hypertension, and serology. RESULTS: None of the markers were associated with cutaneous subgroups of SSc. Concentrations of annexin V non-binding EMPs and annexin V non binding LMPs were negatively correlated to pulmonary diffusing capacity (DLCO) (r = -0.28; p = 0.003; r = -0.26; p = 0.005) and forced vital capacity (FVC) (r = 0.24; p = 0.009; r = -0.29; p = 0.002), driven by patients with limited and diffuse cutaneous disease, respectively. Soluble E-selectin levels correlated negatively to DL(CO) (r = -0.21, p = 0.03) and FVC (r = -0.25; p = 0.007); and soluble P-selectin correlated negatively to DL(CO) (r = -0.23, p = 0.01). CONCLUSION: Negative correlations between annexin V non-binding EMP and LMP concentrations with lung function parameters (DL(CO) and FVC) differed between limited and diffuse cutaneous subsets of SSc, indicative of various pathogeneses of lung involvement in SSc, possibly with a differential role of MPs. PMID- 26265410 TI - "If I Were Nick": Men's Responses to an Interactive Video Drama Series to Support Smoking Cessation. AB - BACKGROUND: Men continue to smoke in greater numbers than women; however, few interventions have been developed and tested to support men's cessation. Men tend to rely on quitting strategies associated with stereotypical manliness, such as willpower, stoicism, and independence, but they may lack the self-efficacy skills required to sustain a quit. In this paper, we describe the development of and reception to an interactive video drama (IVD) series, composed of 7 brief scenarios, to support and strengthen men's smoking cessation efforts. The value of IVD in health promotion is predicated on the evidence that viewers engage with the material when they are presented characters with whom they can personally identify. The video dramatizes the challenges unfolding in the life of the main character, Nick, on the first day of his quit and models the skills necessary to embark upon a sustainable quit. OBJECTIVE: The objective was to describe men's responses to the If I were Nick IVD series as part of a study of QuitNow Men, an innovative smoking cessation website designed for men. Specific objectives were to explore the resonance of the main character of the IVD series with end-users and explore men's perceptions of the effectiveness of the IVD series for supporting their quit self-management. METHODS: Seven brief IVD scenarios were developed, filmed with a professional actor, and uploaded to a new online smoking cessation website, QuitNow Men. A sample of 117 men who smoked were recruited into the study and provided baseline data prior to access to the QuitNow Men website for a 6-month period. During this time, 47 men chose to view the IVDs. Their responses to questions about the IVDs were collected in online surveys at 3 month and 6-month time points and analyzed using descriptive statistics. RESULTS: The majority of participants indicated they related to the main character, Nick. Participants who "strongly agreed" they could relate to Nick perceived significantly higher levels of support from the IVDs than the "neutral" and "disagree" groups (P<.001, d=2.0, P<.001, d=3.1). The "agree" and "neutral" groups were significantly higher on rated support from the videos than the "disagree" (P<.001, d=2.2, P=.01, d=1.5). Participants' perception of the main character was independent of participant age, education attainment, or previous quit attempts. CONCLUSIONS: The findings suggest that IVD interventions may be an important addition to men's smoking cessation programs. Given that the use of IVD scenarios in health promotion is in its infancy, the positive outcomes from this study signal the potential for IVD and warrant ongoing evaluation in smoking cessation and, more generally, men's health promotion. PMID- 26265411 TI - [Persistence in the treatment of overactive bladder (OAB) with Mirabegron in a multicentre clinical study]. AB - OBJECTIVE: The objective of this monitoring was to evaluate persistence in the treatment of patients with overactive bladder syndrome (OAB) using mirabegron. DESIGN: Prospective clinical study. SETTING: 10 gynecological and urological departments in CZE. MATERIALS AND METHODS: This is an analysis of a prospective, multicenter monitoring which started in May 2014 and will continue for 1 year. This monitoring included patients 18 years old who have had symptoms of OAB for minimum 3 months. The patient check-up was performed 6 months (+/-2 weeks) after the first visit. The dosage of mirabegron was 50 mg per day. For the evaluation the treatment efficacy we employed the TS-VAS and PPBC. During the check-up it was ascertained how many patients discontinued the treatment with mirabegron, and reasons for this interruption were established. The statistics were calculated using the software SPSS 20.0. RESULTS: A prospective monitoring was performed on 206 patients. Their mean age was 62.8 years (range 23-89); mean body mass index for the whole group of patients was 27.3. At the check-up 6 months post initiation of treatment it emerged that 55/206 (27%) patiens had discontinued the treatment. The reasons for discontinuation of treatment were: 24/55 (43%) insufficient treatment efficacy, 29/55 (53%) other reasons (the main reasons here were hospitalisation, surgery, gravidity) and 2/55 discontinued therapy because of side effects. The side effects were tachycardia, eye irritation, lower abdominal pain and vasculitis, and they were mild in nature. The termination of the study was 7/28 (25%) in the group of patients without previous treatment before mirabegron. Discontinuation of the treatment in the group of patients with previous anticholinergic treatment was 48/178 (27%). At the evaluation of the efficacy of the treatment during the check-up 6 months after initiation of treatment the mean TS-VAS was 77.5, a decrease of the scale of bothers evaluated by PPBC before treatment from a mean value of 3.56 to a value of 1.77. CONCLUSIONS: Our hypothesis, that persistence in treat-ment with mirabegron would be relatively high due to reduced side effects and better cure effect, was confirmed, and this is the reason for higher rates of persistence in the treatment at 6 months check-up (73%). PMID- 26265412 TI - [Benefits and the accuracy of the intra-operative frozen section at suspected ovarian tumours]. AB - OBJECTIVE: To assess benefits and the accuracy of the intra-operative frozen section for the operative strategy at suspected ovarian tumours. TYPE OF STUDY: Retrospective study. SETTING: Department of Obstetrics and Gynaecology, Faculty of Medicine and Dentistry, Palacky University in Olomouc. MATERIALS AND METHODS: Intraoperative frozen section and final histopathology were compared in 53 patients who underwent operative treatment for suspected ovarian neoplazma. The accuracy of the frozen section findings was evaluated according to the histopatological type of tumours and categories - benign, malignant and borderline tumours. CONCLUSION: In accordance with literature reports a good reliability of the frozen section as for the sensitivity, specificity, positive and negative predictive values were proved. The majority of errors occured in diagnosing mucinous and borderline tumours. PMID- 26265413 TI - [The importance of HE4 in differential diagnosis of endometrial cancer]. AB - OBJECTIVE: The aim of the present study was to evaluate the use of human epididymis protein 4 (HE4) and cancer antigen 125 (CA 125) biomarkers in differential diagnosis of malignant and benign endometrial tumours in a population of Czech women. DESIGN: Prospective study. SETTING: Department of Gynaecology and Obstetrics, Faculty of Medicine at Masaryk University and Faculty Hospital in Brno. METHODS: Our prospective study includes 115 patients with endometrioid adenocarcinoma and 106 patients with benign endometrial tumours in the control group. They were diagnosed with endometrial biopsy in the period from 7/2010 to 6/2013. The patients with cancer underwent definitive surgical treatment to determine the stage of disease. The median and ranges of serum levels were determined in relation to the histological result (benign vs malignant disease). Statistical analysis operates with logarithm values of markers because their distribution is not normal and uses logistic regression. RESULTS: While analysing two groups of patients with different histology, there was demonstrated a statistically significant difference (p < 0.05), only in HE4, by cut-off 48,5 pmol/l there was achieved sensitivity of 87.8%, specificity of 56.6% and negative predictive value of 81.1%. COCLUSION: Diagnostic benefit of HE4 can be considered especially in patients with increased risk of endometrial cancer and in patients with serious internal co-morbidities. HE4 could help in combination with clinical and ultrasound finding in the differentiation of prognostically various groups of patients and in decision-making in relation to the individualization of the treatment plan. However, the optimal cut-off for HE4 has not been solved yet, and to do so, it will require more research with larger studies and their comparative analysis.. PMID- 26265414 TI - [Smoking in pregnancy - negative impacton mother and child Opinions on nicotine substitution]. AB - Cigarette smoking (tobacco abuse) is legal in the Czech Republic and use of this drug is more or less tolerated there. Argumentation about economic benefits of the production and sale of tobacco products in this country is not responsibly given in context with the level of damage to health. The state does not consistently take into action restrictive measures to prevent this negative phenomenon. Even the medical community adopts an indifferent attitude. Although there have been found countless hard evidence about the harmful effects of smoking on the mother and fetus/baby. Even very small amounts of cigarettes has a negative impact on mother, placental perfusion and ultimately the child. The aim of the article is to describe the pathophysiology of tobacco abuse on mother and baby and to simultaneously open a space for discussion about the treatment of smokers during their pregnancy. PMID- 26265415 TI - [The issue of certain infectious diseases of pregnant women in everyday practice Part II. Viral infections]. AB - OBJECT: Authors in their text are bringing the latest published findings on the impact of some of the most common infectious diseases on the course and outcome of pregnancies. DESIGN: Review. CONCLUSIONS: Recommendations for examination, treatment, and management of viral infection in pregnant women, especially from the view of a primary contact gynecologist. PMID- 26265416 TI - Polycystic ovary syndrome and metabolic syndrome. AB - Polycystic ovary syndrome (PCOS) is a heterogeneous disorder, where the main clinical features include menstrual irregularities, sub-fertility, hyperandrogenism, and hirsutism. The prevalence of PCOS depends on ethnicity, environmental and genetic factors, as well as the criteria used to define it. On the other hand, metabolic syndrome is a constellation of metabolic disorders which include mainly abdominal obesity, insulin resistance, impaired glucose metabolism, hypertension and dyslipidaemia. These associated disorders directly increase the risk of Type 2 diabetes mellitus (DMT2), coronary heart disease (CHD), cardiovascular diseases (CVD) and endometrial cancer. Many patients with PCOS have features of metabolic syndrome such as visceral obesity, hyperinsulinaemia and insulin resistance. These place patients with PCOS under high risk of developing cardiovascular disease (CVD), Type 2 diabetes (DMT2) and gynecological cancer, in particular, endometrial cancer. Metabolic syndrome is also increased in infertile women with PCOS. The aim of this review is to provide clear and up to date information about PCOS and its relationship with metabolic syndrome, and the possible interaction between different metabolic disorders. PMID- 26265417 TI - Translation and cross-cultural adaptation of the Pregnancy Physical Activity Questionnaire (PPAQ) to the Brazilian population. AB - OBJECTIVE: To evaluate the total activity performed by women with low-risk pregnancy as well as translate and pursue a cross-cultural adaptation of the Pregnancy Physical Activity Questionnaire (PPAQ) to the Brazilian reality. DESIGN: We conducted a cross-sectional quantitative study including 305 women between 16 and 40 years of age with low-risk pregnancies. SETTING: The Department of Public Health, State University of Ceara, Fortaleza, Brazil. METHODS: We applied an adapted version of PPAQ to assess the levels of physical activity and the intensity in the metabolic equivalent task (MET), which could be distinguished as follows: sedentary (< 1.5 METs), light (1.5-3.0 METs), moderate activity (3.0-6.0 METs), and vigorous activity (>6.0 METs). The Kruskal-Wallis test was used to compare energy expenditure (MET) with socio-demographic variables. RESULTS: More than half of the participants performed activities that were classified as light (51.4%). If we group the activities that were categorized as sedentary and light, this value increases to 74.7%, showing a high prevalence of insufficiently active pregnant women. Lower energy expenditure was observed in the third gestational trimester among pregnant women with lower educational level, single women, and mixed-race women (p < 0.05). CONCLUSION: There is a prevalence of physical inactivity during the three trimesters of pregnancy. The results validate PPAQ for the Brazilian population to serve as a basis for future public policies focused on combating the health problems of mother-infant pairs. PMID- 26265418 TI - [Surrogacy, yes or no? Case report]. AB - OBJECTIVE: Case study of surrogacy which did not come up to client-couple's expectation. DESIGN: Case report. SETTING: Department of Gynaecology and Obstetrics, Uherske Hradiste Hospital a. s., Uherske Hradiste. METHODOLOGY: Description of the case, case study. CONCLUSION: In the Czech Republic, missing legislation when subject matter is surrogacy does not allow to make a complex legal contract. This fact causes legal uncertainty to all participants. Irresponsible approach of doctors, surrogate mother, client-couple, and in the upshot care of disabled child at government expense can be results. PMID- 26265419 TI - [Different outcome in two case reports of births showing symptoms of amniotic fluid embolism in the years 2002 and 2012 in the district hospital of Decin]. AB - This paper presents two case reports of amniotic fluid embolism quite identical in the onset of symptoms, 1,20 hr, respectively 1,40 hr after extraction of the fetus during delivery by caesarean section, both births were induced by prostaglandins. Both newborns were male. One patient died with autopsy providing evidence of massive pulmonary embolism, laboratory findings showed hemolysis. The second patient survived with neurological disorders, laboratory findings temporarily showed nonspecific antibodies. Both patients were subdued to hysterectomy, no trace of amniotic fluid components were found in the uterine vessels in either one of them. PMID- 26265420 TI - Depressive symptoms and social demographic, stress and health risk behaviour among university students in 26 low-, middle- and high-income countries. AB - BACKGROUND: The aim of this study was to determine the prevalence and association between depressive symptoms, sociodemographic, social and health risk variables among undergraduate students in 26 low, middle and high income countries. METHOD: Using anonymous questionnaires, data were collected from 20222 undergraduate university students (mean age 20.8, SD = 2.8) from 27 universities in 26 countries in Africa, Asia, Caribbean and Latin America. RESULTS: Overall study participants had a prevalence of 24.0 % moderate and 12.8 % severe depressive symptoms. In multivariate logistic regression, demographic and social variables (being female gender, low organised religious activity, lack of social support and lack of personal control), stressful or traumatic life events (sexual violence and physical child abuse) and health risk behaviour (tobacco use, insufficient brushing of teeth, irregular sleep duration, increased salt intake, infrequent meals a day, heavy internet use and having sustained an injury) were associated with severe depressive symptoms. CONCLUSION: High rates of depressive symptoms were found. Several risk factors including social and health risk behaviour variables were identified which can be utilised in guiding interventions. PMID- 26265424 TI - Erratum. PMID- 26265425 TI - Highly Branched Poly(beta-Amino Esters): Synthesis and Application in Gene Delivery. AB - Highly branched poly(beta-amino esters) (HPAEs) are developed via a facile and controllable "A2+B3/B2" strategy successfully. As nonviral gene delivery vectors, the performance of HPAEs is superior to the well-studied linear counterpart as well as the leading commercial reagent Superfect. When combined with minicircle DNA construct, HPAEs can achieve ultrahigh gene transfection efficiency, especially in keratinocytes. PMID- 26265421 TI - Self-selected intensity exercise in the treatment of major depression: A pragmatic RCT. AB - OBJECTIVE: The purpose of the study was to determine the therapeutic effect of physical exercise for patients with unipolar depression. Participants took part in an 8-week walking/running aerobic exercise program at a local sports club. METHODS: Forty-six outpatients aged 18-65 years and diagnosed with mild to severe depression (ICD-10 criteria) were randomly assigned to an intervention group or wait list. Treatment as usual was continued. The Hamilton Rating Scale for Depression (HRSD-17) served as the main outcome measure. Secondary outcome measures were Beck Depression Inventory (BDI-II), Fitness Index (FI), and VO(2) max as estimated by Urho Kaleka Kekkonen or UKK 2-km Walk Test. RESULTS: Out of forty-six participants, 24% dropped out. Participants attended 58% of exercise sessions. All randomized participants were included in intention-to-treat (ITT) analysis. Analysis of covariance or ANCOVA showed a large reduction of depressive symptoms in HRSD-17 scores (Cohen's d: 1.8; mean change 8.2, p < .0001). BDI-II (Cohen's d: 0.50; mean change: 4.7, p = 0.09), FI scores (Cohen's d: 0.27; mean change: 5.3, p = 0.08), and VO2 max did not change significantly. CONCLUSIONS: We observed a large and clinically significant change in HRSD-17 scores. Moderate changes in BDI-II scores without clinical significance and small changes in physical fitness assessments were observed. PMID- 26265426 TI - Decementation Rates and the Peri-Implant Tissue Status of Implant-Supported Fixed Restorations Retained via Zinc Oxide Cement: A Retrospective 10-23-Year Study. AB - BACKGROUND: Long-term data on clinical outcomes of restorations attached to implants via zinc oxide (ZnO) cement have been sparse. PURPOSE: The purpose of this study was to retrospectively investigate decementation rates and peri implant tissue status of implant-supported fixed restorations retained by ZnO cement. MATERIALS AND METHODS: Between 1989 and 2003, 63 partially edentulous patients received 93 implants. Of these, 27 patients received 36 screwed single crowns (SC) and served as a control (C group). The other 36 patients had their restorations cemented using ZnO cement. They were subdivided into a SC group and a fixed dental prosthesis (FDP) group. After between 10 and 23 years (mean: 13.22 +/- 3.21), all decementation events and peri-implant soft tissue status were evaluated using patient records. RESULTS: Decementation was assessed in 57 implants supporting 30 SCs and 16 FDPs. Five cases of decementation (8.77%) were recorded after a mean of 9.27 +/- 7.05 years (range: 4.81-21.79). In the control group of vertically screwed SCs, five events of screw loosening (13.89%) were recorded in five patients (18.52%) after a mean of 5.84 +/- 5.96 years (range: 0.56-15.05) within a 14.30 year observation period. No cases of peri-implantitis were observed in any group. The mean values of periodontal probing depths and bleeding on probing (BOP+) were 3.74 mm and 31.58%, respectively, for ZnO cemented restorations, versus 3.76 mm and 25%, respectively, for the C group. No significant correlations regarding technical/biologic complications between the groups were detected. CONCLUSIONS: Within the limitations of this study, we conclude that the use of ZnO cement provides sufficient retention of implant supported fixed restorations over long periods without biologic complications in form of peri-implantitis. PMID- 26265427 TI - Gender differences in irritable bowel syndrome: the interpersonal connection. AB - BACKGROUND: While irritable bowel syndrome (IBS) affects women more than men, the reasons are unclear. Research on the female preponderance of IBS has focused on gender differences in sex-linked biological processes; much less attention has been paid to the role of psychosocial factors. Interpersonal difficulties may be one source of stress that may significantly impact on women with IBS. Because of the importance that women attach to relationships, we suspected they would be more reactive to interpersonal stress. METHODS: A total of 283 (M age = 41 years, F = 80%), Rome III-diagnosed IBS patients completed a test battery that included the IBS Symptom Severity Scale, McGill Pain Questionnaire, Inventory of Interpersonal Problems (IIP), interpersonal support evaluation list (social support), Negative Interactions Scale, Brief Symptom Inventory (distress), Beck Depression Inventory, Anxiety Sensitivity Inventory, and IBS-Quality of Life as part of baseline assessment of an NIH trial. KEY RESULTS: Males scored higher on two IIP scales reflecting a hostile-dominant interpersonal pattern, and reported less social support. The quality of relationship problems (more interpersonal difficulties, lower support) correlated with IBS symptom severity as measured mainly by gastroenterologists. CONCLUSIONS & INFERENCES: Male, not female, IBS patients reported more interpersonal difficulties. Male patients-a population for whom little is known-are characterized by hostile-dominant interpersonal problems. This finding has clinical importance, given that relationship problems may influence MDs' estimation of IBS symptom severity and undermine the physician patient relationship. PMID- 26265428 TI - Expression and characterization of a cellobiohydrolase (CBH7B) from the thermophilic fungus Thielavia terrestris in Pichia pastoris. AB - The gene encoding a cellobiohydrolase 7B (CBH7B) of the thermophilic fungus Thielavia terrestris was identified, subcloned, and expressed in Pichia pastoris. CBH7B encoded 455 amino acid residues with a molecular mass of 51.8 kDa. Domain analysis indicated that CBH7B contains a family 7 glycosyl hydrolase catalytic core but lacks a carbohydrate-binding module. Purified CBH7B exhibited optimum catalytic activity at pH 5.0 and 55 degrees C with 4-methylumbelliferryl cellobioside as the substrate and retained 85% of its activity following 24 H incubation at 50 degrees C. Despite the lack of activity toward microcrystalline substrates, this enzyme worked synergistically with the commercial enzyme cocktail Cellic(r) CTec2 to enhance saccharification by 39% when added to a reaction mixture containing 0.25% alkaline pretreated oil palm empty fruit bunch (OPEFB). Attenuated total reflectance Fourier transform infrared spectroscopy suggested a reduction of lignin and crystalline cellulose in OPEFB samples supplemented with CBH7B. Scanning electron microscopy revealed greater destruction extent of OPEFB strands in samples supplemented with CBH7B as compared with the nonsupplemented control. Therefore, CBH7B has the potential to complement commercial enzymes in hydrolyzing lignocellulosic biomass. PMID- 26265429 TI - Language-specific memory for everyday arithmetic facts in Chinese-English bilinguals. AB - The role of language in memory for arithmetic facts remains controversial. Here, we examined transfer of memory training for evidence that bilinguals may acquire language-specific memory stores for everyday arithmetic facts. Chinese-English bilingual adults (n = 32) were trained on different subsets of simple addition and multiplication problems. Each operation was trained in one language or the other. The subsequent test phase included all problems with addition and multiplication alternating across trials in two blocks, one in each language. Averaging over training language, the response time (RT) gains for trained problems relative to untrained problems were greater in the trained language than in the untrained language. Subsequent analysis showed that English training produced larger RT gains for trained problems relative to untrained problems in English at test relative to the untrained Chinese language. In contrast, there was no evidence with Chinese training that problem-specific RT gains differed between Chinese and the untrained English language. We propose that training in Chinese promoted a translation strategy for English arithmetic (particularly multiplication) that produced strong cross-language generalization of practice, whereas training in English strengthened relatively weak, English-language arithmetic memories and produced little generalization to Chinese (i.e., English training did not induce an English translation strategy for Chinese language trials). The results support the existence of language-specific strengthening of memory for everyday arithmetic facts. PMID- 26265430 TI - Is mental effort exertion contagious? AB - The presence of another person can influence task performance. What is, however, still unclear is whether performance also depends on what this other person is doing. In two experiments, two participants (A and B) jointly performed a Simon task, and we selectively manipulated the difficulty of the task for participant A only. This was achieved by presenting A with 90% congruent trials (creating an easy task requiring low effort investment) or 10% congruent trials (creating a difficult task requiring high effort investment). Although this manipulation is irrelevant for the task of participant B, we nevertheless observed that B exerted more mental effort when participant A performed the difficult version of the task, compared to the easy version. Crucially, in Experiment 2 this was found to be the case even when participants could not see each other's stimuli. These results provide a first compelling demonstration that the exertion of effort is contagious. PMID- 26265431 TI - Ultrasonographic Median Nerve Changes After Repeated Wheelchair Transfers in Persons With Paraplegia: Relationship With Subject Characteristics and Transfer Skills. AB - BACKGROUND: Wheelchair users with spinal cord injuries are susceptible to peripheral neuropathies from overuse, yet no studies have established a relationship between median neuropathy and wheelchair transfers. A more thorough understanding of how transfers and technique contribute to pathologic conditions may guide interventions that curtail its development. OBJECTIVE: To evaluate the effects of repeated transfers on ultrasound markers for carpal tunnel syndrome (CTS) in people with spinal cord injuries and to relate changes to subject characteristics and transfer skills. DESIGN: Cross-sectional, repeated measures. SETTING: Research laboratory and national wheelchair sporting events. PARTICIPANTS: A convenience sample of 30 wheelchair users with nonprogressive paraplegia were recruited via research registries and at the 2013 National Veterans Wheelchair Games and 2014 Paralyzed Veterans of America Buckeye Games. Participants were older than 18 years and could complete transfers independently within 30 seconds without use of their leg muscles. METHODS: Demographic questionnaires and physical examinations for CTS were completed. Quantitative ultrasound techniques were used to measure changes in the median nerve after a repeated-transfers protocol. The Transfer Assessment Instrument (TAI) was completed to quantify transfer ability. MAIN OUTCOME MEASUREMENTS: Median nerve cross-sectional area at the level of the pisiform (PCSA) and swelling ratio (SR), transfer quality, and skills via the TAI. RESULTS: PCSA increased after repeated transfers (P < .025). Participants who used safe hand positions had a lower baseline SR (beta = -0.728; P < .01). Participants with a higher body weight had a lower baseline SR provided they performed higher quality transfers. Participants who scooted to the front of the seat prior to transferring (TAI item 7; beta = 0.144; P < .05) and who weighed more (beta = 0.142; P < .05) exhibited greater increases in PCSA in response to transfers. CONCLUSIONS: An acute increase was observed in median nerve CSA at the pisiform after repeated wheelchair transfers. Changes were greater in persons with higher body weight and in persons who did not perform certain transfer skills correctly (according to the TAI). It is possible that these factors contribute to chronic injury and possibly CTS. PMID- 26265432 TI - Examining Early Behavioral Persistence as a Dynamic Process: Correlates and Consequences Spanning Ages 3-10 Years. AB - We investigated systematic changes in 3-year-olds' effortful persistence in a dyadic problem-solving context and explored their correlates (i.e., parenting behavior and demographic characteristics at 3 years) and consequences (i.e., child externalizing behavior at 3, 6, and 10 years) within a sample of 241 middle income families (118 girls). Results indicated that children may be grouped into three classes based on their behavioral profiles of persistence. Children who were highly persistent over the course of the task were more likely to have higher levels of IQ and mothers who were observed to be more behaviorally responsive than those who showed consistently low levels of task-related behavior. Additionally, children who demonstrated stably low levels of persistence were rated by teachers to display more externalizing behavior at 6 and 10 years than those in the other groups. Profiles of persistence did not predict concurrent levels of child externalizing behavior at the age of 3 years. The findings are discussed with respect to expanding the scope of research on child self-regulation by defining it as a time based construct and tracking its dynamic changes. PMID- 26265433 TI - Emotional Intelligence and Nurse Recruitment: Rasch and confirmatory factor analysis of the trait emotional intelligence questionnaire short form. AB - AIM: To examine the construct validity of the Trait Emotional Intelligence Questionnaire Short form. BACKGROUND: Emotional intelligence involves the identification and regulation of our own emotions and the emotions of others. It is therefore a potentially useful construct in the investigation of recruitment and retention in nursing and many questionnaires have been constructed to measure it. DESIGN: Secondary analysis of existing dataset of responses to Trait Emotional Intelligence Questionnaire Short form using concurrent application of Rasch analysis and confirmatory factor analysis. METHOD: First year undergraduate nursing and computing students completed Trait Emotional Intelligence Questionnaire-Short Form in September 2013. Responses were analysed by synthesising results of Rasch analysis and confirmatory factor analysis. RESULTS: Participants (N = 938) completed Trait Emotional Intelligence Questionnaire Short form. Rasch analysis showed the majority of the Trait Emotional Intelligence Questionnaire-Short Form items made a unique contribution to the latent trait of emotional intelligence. Five items did not fit the model and differential item functioning (gender) accounted for this misfit. Confirmatory factor analysis revealed a four-factor structure consisting of: self-confidence, empathy, uncertainty and social connection. All five misfitting items from the Rasch analysis belonged to the 'social connection' factor. CONCLUSIONS: The concurrent use of Rasch and factor analysis allowed for novel interpretation of Trait Emotional Intelligence Questionnaire Short form. Much of the response variation in Trait Emotional Intelligence Questionnaire Short form can be accounted for by the social connection factor. Implications for practice are discussed. PMID- 26265434 TI - A metabolomics strategy to explore urinary biomarkers and metabolic pathways for assessment of interaction between Danhong injection and low-dose aspirin during their synergistic treatment. AB - The drug combination of Danhong injection (DHI) and low-dose aspirin (ASA) was frequently applied for the treatment of cardiovascular and cerebrovascular diseases. Due to the drug interactions, a lot of potential benefits and risks might exist side by side in the course of combination therapy. However, there had been no studies of interaction between DHI and ASA. Metabolomics was a powerful tool to explore endogenous biomarkers and metabolic pathways. In present study, metabolic profiling with ultra-high-performance liquid chromatography coupled to quadrupole time of flight mass spectrometry (UHPLC-QTOF/MS) coupled with multivariate statistical analysis was performed to provide insight into understanding the interaction between DHI and low-dose ASA. Eleven potential biomarkers of three types were identified and seven metabolic pathways were constructed. The results showed that the interaction between DHI and low-dose ASA during synergistic treatment indeed affected some key endogenous biomarkers and metabolic pathways, which could not happen when DHI or low-dose ASA was used alone. The quality and quantity of endogenous metabolite were both influenced by interaction between DHI and low-dose ASA. In details, the amount of flavin mononucleotide, L-2, 4-diaminobutyric acid (DABA) and 4-aminohippuric acid were significantly increased. On the contrary, the amount of 3-methyluridine, 4, 6 dihydroxyquinoline, cortolone-3-glucuronide, and serotonin were significantly decreased. Furthermore, O-phosphotyrosine, 3-methyl-2-butenal, indoxyl sulfate and dolichyl diphosphate were disappeared in urine. As to metabolic pathways, riboflavin metabolism, pentose and glucuronate interconversions, and tryptophan metabolism were all significantly influenced. The emerging alterations of biomarkers and metabolic pathways were associated with a lot of drugs and diseases based on literature researches, which might influence the co administration of other drugs or the treatments of relevant diseases. Our paper presented some hints to uncover the mechanism of interaction between DHI and low dose ASA, which would provide some references for application of DHI and low-dose ASA combination. PMID- 26265435 TI - The effect of cognitive appraisal in middle-aged women stroke survivors and the psychological health of their caregivers: a follow-up study. AB - AIMS AND OBJECTIVES: This study identified the factors that affect health-related quality of life at one and six months post-stroke in women who have undergone a mild stroke and that affect their informal caregivers' psychological health status. BACKGROUND: Middle-aged women perform the main care roles in a family. When they suffer a stroke, it upsets the equilibrium of their family life. DESIGN: This is a longitudinal design. METHODS: This prospective follow-up study recruited 41 middle-aged women stroke survivors (mean age = 54.95, SD = 9.63) and their informal caregivers (mean age = 41.56, SD = 15.93). The Short-Form Health Survey (SF-36) was used to assess stroke survivor's health-related quality of life, and the Chinese Health Questionnaire was used to measure the level of depression of the stroke survivor's informal caregiver. Data were analysed through descriptive statistics, Wilcoxon signed-rank tests and the generalised estimating equation approach for modelling repeatedly measures. RESULTS: All stroke survivors showed significant improvement in the physical component summary of the health-related quality of life at one and six months after stroke, but there was no significant difference in the mental component summary. In addition, there was no significant difference in the health of the informal caregivers of the women over time. Generalised estimating equation analysis showed that the most important determinant of mental component summary of health-related quality of life among women stroke survivors was cognitive appraisal. The informal caregivers' most important determinants of health status, as measured by level of depression, were their sense of coherence, burden and patients' mental component summary of the health-related quality of life. CONCLUSION: This study highlights the impact of cognitive appraisal in determining health-related quality of life of women stroke survivors and how it affects their caregivers' mental health. RELEVANCE TO CLINICAL PRACTICE: The findings of this study may contribute to home care nurses' understanding the importance of the psychosocial impact of the stroke for the survivor and their ability to help the surviving women to promote the confidence needed for self-care, which will contribute to their quality of life and affect their caregivers' health. PMID- 26265436 TI - Serotonergic gene variation in substance use pharmacotherapy: a systematic review. AB - Drug addiction is a serious disease with damaging effects on the brain and physical health. Despite the increase in the number of affected individuals, there are few effective pharmacological treatment options for substance use disorders. The study of the influence of an individual's genetic features on the treatment response may help to identify more efficacious treatment options. This systematic review focuses on the serotonergic system because of its relevant role in mood and impulse control disorders, and its contribution to the development and maintenance of drug use disorders. In particular, we examine the role of serotonergic genes in the response to pharmacotherapy for alcohol, cocaine and nicotine addiction. Current evidence suggests that genetic variability of the serotonergic biosynthesis enzyme tryptophan hydroxylase 2 (TPH2) and the serotonin transporter (SLC6A4) genes mediates the efficacy of several addiction treatments, such as ondansetron and disulfiram, and the antidepressants bupropion, nortriptyline and sertraline. PMID- 26265437 TI - MicroRNA-1908 functions as a glioblastoma oncogene by suppressing PTEN tumor suppressor pathway. AB - BACKGROUND: We aimed to investigate whether miRNA-1908 is an oncogene in human glioblastoma and find the possible mechanism of miR-1908. METHODS: We investigated the growth potentials of miRNA-1908-overexpressing SW-1783 cells in vitro and in vivo. In order to identify the target molecule of miRNA-1908, a luciferase reporter assay was performed, and the corresponding downstream signaling pathway was examined using immunohistochemistry of human glioblastoma tissues. We also investigated the miRNA-1908 expression in 34 patients according to the postoperative risk of recurrence. RESULTS: The overexpression of miRNA 1908 significantly promoted anchorage-independent growth in vitro and significantly increased the tumor forming potential in vivo. MiRNA-1908 significantly suppressed the luciferase activity of mRNA combined with the PTEN 3'-UTR. Furthermore, the expression levels of miRNA-1908 were significantly increased in the patients with a high risk of recurrence compared to that observed in the low-risk patients, and this higher expression correlated with a poor survival. CONCLUSIONS: miRNA-1908 functions as an oncogene in glioblastoma by repressing the PTEN pathway. MiR-1908 is a potential new molecular marker for predicting the risk of recurrence and prognosis of glioblastoma. PMID- 26265438 TI - Alternative splicing of synuclein gamma in endometrial cancer: identification of a novel isoform. AB - Synuclein gamma (SNCG) is under consideration as a potential biomarker in cancer biology. Up to date four different SNCG variants are described. Due to growing evidence suggesting correlations between aberrant alternative splicing processes and cancer progression, we investigated the effects of peritumoural conditions on expression pattern of SNCG in endometrial cancer (EC) in vitro. Compared to breast cancer cell lines, mRNA expression levels of all known SNCG isoforms 1-4 are significantly reduced in EC cell lines. We identified a novel alternatively spliced variant of isoform 2 (isoform 2 short) which is found highly expressed in EC cell lines. Hypoxia and acidosis trigger an up-regulation of isoform 2 short. EC cell lines are characterized by low SNCG protein levels under control conditions, but exhibit a significant increase triggered by hypoxia and acidosis. In addition we analysed the potential association between SNCG protein expression and clinico-pathological parameters in human EC samples. Our findings indicate a grade-dependent induction of SNCG protein expression in endometrial cancer. We identified for the first time a novel isoform of SNCG that is found specifically expressed in EC. Our results also strongly indicate the existence of a corresponding protein of isoform 2 short that potentially plays a critical role in EC cancer progression. PMID- 26265439 TI - Metformin inhibits cell cycle progression of B-cell chronic lymphocytic leukemia cells. AB - B-cell chronic lymphocytic leukemia (CLL) was believed to result from clonal accumulation of resting apoptosis-resistant malignant B lymphocytes. However, it became increasingly clear that CLL cells undergo, during their life, iterative cycles of re-activation and subsequent clonal expansion. Drugs interfering with CLL cell cycle entry would be greatly beneficial in the treatment of this disease. 1, 1-Dimethylbiguanide hydrochloride (metformin), the most widely prescribed oral hypoglycemic agent, inexpensive and well tolerated, has recently received increased attention for its potential antitumor activity. We wondered whether metformin has apoptotic and anti-proliferative activity on leukemic cells derived from CLL patients. Metformin was administered in vitro either to quiescent cells or during CLL cell activation stimuli, provided by classical co culturing with CD40L-expressing fibroblasts. At doses that were totally ineffective on normal lymphocytes, metformin induced apoptosis of quiescent CLL cells and inhibition of cell cycle entry when CLL were stimulated by CD40-CD40L ligation. This cytostatic effect was accompanied by decreased expression of survival- and proliferation-associated proteins, inhibition of signaling pathways involved in CLL disease progression and decreased intracellular glucose available for glycolysis. In drug combination experiments, metformin lowered the apoptotic threshold and potentiated the cytotoxic effects of classical and novel antitumor molecules. Our results indicate that, while CLL cells after stimulation are in the process of building their full survival and cycling armamentarium, the presence of metformin affects this process. PMID- 26265440 TI - A novel HMGA1-CCNE2-YAP axis regulates breast cancer aggressiveness. AB - High Mobility Group A1 (HMGA1) is an architectural chromatin factor that promotes neoplastic transformation and progression. However, the mechanism by which HMGA1 exerts its oncogenic function is not fully understood. Here, we show that cyclin E2 (CCNE2) acts downstream of HMGA1 to regulate the motility and invasiveness of basal-like breast cancer cells by promoting the nuclear localization and activity of YAP, the downstream mediator of the Hippo pathway. Mechanistically, the activity of MST1/2 and LATS1/2, the core kinases of the Hippo pathway, are required for the HMGA1- and CCNE2-mediated regulation of YAP localization. In breast cancer patients, high levels of HMGA1 and CCNE2 expression are associated with the YAP/TAZ signature, supporting this connection. Moreover, we provide evidence that CDK inhibitors induce the translocation of YAP from the nucleus to the cytoplasm, resulting in a decrease in its activity. These findings reveal an association between HMGA1 and the Hippo pathway that is relevant to stem cell biology, tissue homeostasis, and cancer. PMID- 26265442 TI - Heightened risk of preterm birth and growth restriction after a first-born son. AB - PURPOSE: In Scandinavia, delivery of a first-born son elevates the risk of preterm delivery and intrauterine growth restriction of the next-born infant. External validity of these results remains unclear. We test this hypothesis for preterm delivery and growth restriction using the linked California birth cohort file. We examined the hypothesis separately by race and/or ethnicity. METHODS: We retrieved data on 2,852,976 births to 1,426,488 mothers with at least two live births. Our within-mother tests applied Cox proportional hazards (preterm delivery, defined as less than 37 weeks gestation) and linear regression models (birth weight for gestational age percentiles). RESULTS: For non-Hispanic whites, Hispanics, Asians, and American Indian and/or Alaska Natives, analyses indicate heightened risk of preterm delivery and growth restriction after a first-born male. The race-specific hazard ratios for preterm delivery range from 1.07 to 1.18. Regression coefficients for birth weight for gestational age percentile range from -0.73 to -1.49. The 95% confidence intervals for all these estimates do not contain the null. By contrast, we could not reject the null for non Hispanic black mothers. CONCLUSIONS: Whereas California findings generally support those from Scandinavia, the null results among non-Hispanic black mothers suggest that we do not detect adverse outcomes after a first-born male in all racial and/or ethnic groups. PMID- 26265441 TI - Phospho-T356RB1 predicts survival in HPV-negative squamous cell carcinoma of the head and neck. AB - Locally advanced squamous cell carcinoma of the head and neck (SCCHN) that is not associated with human papillomavirus (HPV) has a poor prognosis in contrast to HPV-positive disease. To better understand the importance of RB1 activity in HPV negative SCCHN, we investigated the prognostic value of inhibitory CDK4/6 phosphorylation of RB1 on threonine 356 (T356) in archival HPV-negative tumor specimens from patients who underwent surgical resection and adjuvant radiation. We benchmarked pT356RB1 to total RB1, Ki67, pT202/Y204ERK1/2, and TP53, as quantified by automatic quantitative analysis (AQUA), and correlated protein expression with tumor stage and grade. High expression of pT356RB1 but not total RB1 predicted reduced overall survival (OS; P = 0.0295), indicating the potential relevance of post-translational phosphorylation. Paired analysis of The Cancer Genome Atlas (TCGA) data for regulators of this RB1 phosphorylation identified loss or truncating mutation of negative regulator CDKN2A (p16) and elevated expression of the CDK4/6 activator CCND1 (cyclin D) as also predicting poor survival. Given that CDK4/6 inhibitors have been most effective in the context of functional RB1 and low expression or deletion of p16 in other tumor types, these data suggest such agents may merit evaluation in HPV-negative SCCHN, specifically in cases associated with high pT356RB1. PMID- 26265443 TI - "We can lose our life for the abortion": exploring the dynamics shaping abortion care in peri-urban Yangon, Myanmar. AB - OBJECTIVES: Induced abortion in Myanmar is severely legally restricted and permissible only to save a woman's life. As a result, unsafe abortion is common and contributes significantly to maternal mortality. Our overall study aimed to explore women's reproductive health needs in peri-urban Yangon, a dynamic series of townships on the periphery of the country's largest city characterized by poor infrastructure, slum settlements and a mobile, migrant population. In this paper, we focus specifically on the perceptions, opinions and experiences of both adult women and key informants with respect to induced abortion and postabortion care in peri-urban Yangon. STUDY DESIGN: In 2014, we conducted 18 key informant interviews with individuals working in reproductive health in peri-urban Yangon and seven focus group discussions with health service providers (n=2) and adult women (n=5). We analyzed these data for content and themes using a multiphased iterative approach. RESULTS: In peri-urban Yangon, unsafe abortion appears to be common and is largely provided by traditional birth attendants. Women use a range of mechanical, medication and traditional methods, often in combination. Postabortion care is available but misinformation and fear of harassment keep many women from accessing timely care. CONCLUSION: Efforts to reform the highly restrictive abortion law in Myanmar combined with implementation of harm reduction strategies have the potential to greatly improve a neglected area of women's health. Future research on the cost of unsafe abortion to the public sector could be instrumental in achieving legal and service delivery reform. IMPLICATIONS: Measures to increase access to safe, legal abortion care and reduce harm from unsafe abortion need to be expanded. Developing strategies to liberalize Myanmar's abortion law, raising awareness about misoprostol, training clinicians to provide woman-centered postabortion care and documenting the cost of unsafe abortion to the public sector appear warranted. PMID- 26265444 TI - Neuron matters: electric activation of neuronal tissue is dependent on the interaction between the neuron and the electric field. AB - In laboratory research and clinical practice, externally-applied electric fields have been widely used to control neuronal activity. It is generally accepted that neuronal excitability is controlled by electric current that depolarizes or hyperpolarizes the excitable cell membrane. What determines the amount of polarization? Research on the mechanisms of electric stimulation focus on the optimal control of the field properties (frequency, amplitude, and direction of the electric currents) to improve stimulation outcomes. Emerging evidence from modeling and experimental studies support the existence of interactions between the targeted neurons and the externally-applied electric fields. With cell-field interaction, we suggest a two-way process. When a neuron is positioned inside an electric field, the electric field will induce a change in the resting membrane potential by superimposing an electrically-induced transmembrane potential (ITP). At the same time, the electric field can be perturbed and re-distributed by the cell. This cell-field interaction may play a significant role in the overall effects of stimulation. The redistributed field can cause secondary effects to neighboring cells by altering their geometrical pattern and amount of membrane polarization. Neurons excited by the externally-applied electric field can also affect neighboring cells by ephaptic interaction. Both aspects of the cell-field interaction depend on the biophysical properties of the neuronal tissue, including geometric (i.e., size, shape, orientation to the field) and electric (i.e., conductivity and dielectricity) attributes of the cells. The biophysical basis of the cell-field interaction can be explained by the electromagnetism theory. Further experimental and simulation studies on electric stimulation of neuronal tissue should consider the prospect of a cell-field interaction, and a better understanding of tissue inhomogeneity and anisotropy is needed to fully appreciate the neural basis of cell-field interaction as well as the biological effects of electric stimulation. PMID- 26265445 TI - Therapeutic drug monitoring and the conservative management of chronic tuberculous empyema: case report and review of the literature. AB - BACKGROUND: Chronic tuberculous empyema (CTE) is a rare and unusual, low grade and protracted, infection of the pleural space resulting in marked thickening, even calcification of the visceral and parietal pleura. Historically its management has been extraordinarily challenging. Differential penetration of anti TB drugs into the pleural space has resulted in acquired drug resistance and surgery to remove the empyema or close a complicating bronchopleural fistula (BPF) has been technically difficult or unacceptably hazardous. On the basis of limited experience, the combination of tube thoracostomy or catheter drainage and high-end dosing of anti-TB drugs has been recommended as an initial approach to these lesions. Herein we report the first well documented case of closure of a BPF and cure of a CTE using this approach. The chances of a favorable outcome are improved, we suggest, by using therapeutic drug monitoring (TDM) to guide high end drug dosing. CASE PRESENTATION: An 84 year old male immigrant to Canada from Croatia was diagnosed with a CTE after he developed a BPF. The diagnosis was made 62 years after what was, in retrospect, an episode of tuberculous pleurisy. He was treated with computed tomography-guided catheter drainage and TDM-guided high end dosed anti-TB drugs (serum and pleural fluid drug concentrations) over a 10 month period. Sustained closure of the BPF and mycobacteriologic cure of the CTE was achieved. Drug concentrations in the present case and all other reported cases are summarized and interpreted. CONCLUSION: When serum concentrations of the anti-TB drugs isoniazid, pyrazinamide and ethambutol at the high end of the normal range are achieved, pleural fluid concentrations at the low end of the normal range may be anticipated in CTE. Though highly protein bound drugs such as rifampin and moxifloxacin appear to penetrate CTEs less well, their free concentrations in the pleural space may be proportionately higher on account of lower protein concentrations. Interventional radiology and TDM increase the chances that conservative management of CTE will be successful. PMID- 26265446 TI - The Mathematical Theory of Diffusion and Reaction in Enzymes Immoblized Artificial Membrane. The Theory of the Non-Steady State. AB - In this paper, mathematical model pertaining to the decomposition of enzyme substrate complex in an artificial membrane is discussed. Here the transport through liquid membrane phases is considered. The model involves the system of non-linear reaction diffusion equations. The non-linear terms in this model are related to Michaelis-Menten reaction scheme. Approximate analytical expressions for the concentrations of substrate and product have been derived by solving the system of non-linear reaction diffusion equations using new approach of homotopy perturbation method for all values of Michaelis-Menten constant, diffusion coefficient, and rate constant. Approximate flux expression for substrate and product for non-steady-state conditions are also reported. A comparison of the analytical approximation and numerical simulation is also presented. The results obtained in this work are valid for the entire solution domain. PMID- 26265447 TI - Multicentre randomized clinical trial to investigate the cost-effectiveness of an allogeneic single-donor fibrin sealant after coronary artery bypass grafting (FIBER Study). AB - BACKGROUND: Reduction of blood transfusion in cardiac surgery is an important target. The aim of this study was to investigate the cost-effectiveness of the use of CryoSeal(r), an allogeneic single-donor fibrin sealant, in patients undergoing coronary artery bypass grafting (CABG). METHODS: This randomized clinical study involved seven cardiac surgery centres in the Netherlands. Patients undergoing elective isolated CABG with the use of at least one internal thoracic artery (ITA) graft were assigned randomly to receive either CryoSeal(r) (5 ml per ITA bed) or no CryoSeal(r). Primary efficacy endpoints were units of transfused red blood cells, fresh frozen plasma and platelet concentrates, and duration of intensive care unit stay. Secondary efficacy endpoints were 48-h blood loss, reoperation for bleeding, mediastinitis, 30-day mortality and duration of hospital stay. RESULTS: Between March 2009 and January 2012, 1445 patients were randomized. The intention-to-treat (ITT) population comprised 1436 patients; the per-protocol (PP) population 1292. In both the ITT and the PP analysis, no significant difference between the treatment groups was observed for any of the primary and secondary efficacy endpoints. In addition, no significant difference between the groups was seen in the proportion of transfused patients. Estimated CryoSeal(r) costs were ?822 (95 per cent c.i. ?808 to ?836) per patient, which translated to ?72,000 per avoided transfusion (unbounded 95 per cent c.i.). CONCLUSION: The use of the fibrin sealant CryoSeal(r) did not result in health benefits. Combined with the high cost per avoided transfusion, this study does not support the implementation of routine CryoSeal(r) use in elective isolated CABG. REGISTRATION NUMBER: NTR1386 ( http://www.trialregister.nl). PMID- 26265448 TI - Mimicking disruption of brain-immune system-joint communication results in collagen type II-induced arthritis in non-susceptible PVG rats. AB - The brain-immune system-joint communication is disrupted during collagen type II (CII) arthritis in DA rats. Since PVG rats are not susceptible to arthritis induction, comparison of hypothalamic and peripheral neuro-endocrine and immune responses between immunized DA and PVG rats might help to explain their different susceptibility to develop the disease. PVG and DA rats were immunized with CII. Corticosterone, neurotransmitters, anti-CII antibodies, and cytokine concentrations in plasma, and hypothalamic neurotransmitters and cytokines were determined by ELISA, Luminex, HPLC and RT-qPCR. Adrenalectomy or sham-operation was performed in PVG and DA rats 14 days before immunization. Basal plasma corticosterone and adrenaline concentrations were significantly higher, and plasma cytokines and hypothalamic noradrenaline were lower in PVG rats than in DA rats. While DA rats developed severe arthritis upon immunization (maximum score 16), only 12 out of 28 PVG rats showed minimal symptoms (score 1-2). The density of sympathetic nerve fibers in arthritic joints of DA rats markedly decreased, but it remained stable in immunized PVG rats. The ratio corticosterone to IL 1beta levels in plasma was markedly higher in immunized PVG rats than in arthritic DA rats. Adrenalectomy resulted in severe arthritis in PVG rats upon immunization with CII. While DA rats show an altered immune-brain communication that favors the development of arthritis, PVG rats express a protective neuro endocrine milieu, particularly linked to the basal tone of the HPA axis. Mimicking disruption of this axis elicits arthritis in non-susceptible PVG rats. PMID- 26265449 TI - RAF-1 promotes survival of thyroid cancer cells harboring RET/PTC1 rearrangement independently of ERK activation. AB - Thyroid cancer (TC) is frequently associated with BRAF or RAS oncogenic mutations and RET/PTC rearrangements, with aberrant RAF-MEK-ERK and/or PI3K pathway activation. BRAF underlies ERK activation in most TC cells, but not in TPC-1 cells with RET/PTC1 rearrangement. Here, we show that depletion of RAF-1, a RAF family member with a poorly defined role in TC, decreases proliferation and increases apoptosis in TPC-1 cells and, less significantly, in cells harboring a BRAF(V600E) or HRAS(G13R) mutations, but without affecting ERK activation. We further demonstrate that constitutive activation of ERKs in TPC-1 cells is not caused by mutations in 50 oncogenes and tumor suppressors prone to activate the ERK pathway, or affected by inhibition of BRAF, MEK1/2 or PI3K. Our data indicate that RAF-1 is important for the survival of TPC-1 cells independently of the classical MEK1/2-ERK activation, offering new perspectives on RET/PTC signaling and for the therapy of thyroid cancers. PMID- 26265450 TI - Gonadal soma-derived factor (gsdf), a TGF-beta superfamily gene, induces testis differentiation in the teleost fish Oreochromis niloticus. AB - The Nile tilapia, Oreochromis niloticus, is a gonochoristic teleost fish with an XX/XY genetic system and is an excellent model for gonadal sex differentiation. In the present study, we screened novel genes that were expressed predominantly in either XY or XX undifferentiated gonads during the critical period for differentiation of gonads into ovaries or testes using microarray screening. We focused on one of the isolated 12 candidate genes, #9475, which was an ortholog of gsdf (gonadal soma-derived factor), a member of the transforming growth factor beta superfamily. #9475/gsdf showed sexual dimorphism in expression in XY gonads before any other testis differentiation-related genes identified in this species thus far. We also overexpressed the #9475/gsdf gene in XX tilapia, and XX tilapia bearing the #9475/gsdf gene showed normal testis development, which suggests that #9475/gsdf plays an important role in male determination and/or differentiation in tilapia. PMID- 26265451 TI - Comparison of Computerized Patients versus Live Moulaged Actors for a Mass casualty Drill. AB - INTRODUCTION: Multiple modalities for simulating mass-casualty scenarios exist; however, the ideal modality for education and drilling of mass-casualty incident (MCI) triage is not established. Hypothesis/Problem Medical student triage accuracy and time to triage for computer-based simulated victims and live moulaged actors using the pediatric version of the Simple Triage and Rapid Treatment (JumpSTART) mass-casualty triage tool were compared, anticipating that student performance and experience would be equivalent. METHODS: The victim scenarios were created from actual trauma records from pediatric high-mechanism trauma presenting to a participating Level 1 trauma center. The student-reported fidelity of the two modalities was also measured. Comparisons were done using nonparametric statistics and regression analysis using generalized estimating equations. RESULTS: Thirty-three students triaged four live patients and seven computerized patients representing a spectrum of minor, immediate, delayed, and expectant victims. Of the live simulated patients, 92.4% were given accurate triage designations versus 81.8% for the computerized scenarios (P=.005). The median time to triage of live actors was 57 seconds (IQR=45-66) versus 80 seconds (IQR=58-106) for the computerized patients (P<.0001). The moulaged actors were felt to offer a more realistic encounter by 88% of the participants, with a higher associated stress level. CONCLUSION: While potentially easier and more convenient to accomplish, computerized scenarios offered less fidelity than live moulaged actors for the purposes of MCI drilling. Medical students triaged live actors more accurately and more quickly than victims shown in a computerized simulation. PMID- 26265452 TI - The effects of repetitive transcranial magnetic stimulation in obese females with binge eating disorder: a protocol for a double-blinded, randomized, sham controlled trial. AB - BACKGROUND: Binge eating disorder is a new category in DSM-5 and highly associated with higher body mass index. The neural mechanisms that underlie binge eating are of great interest in order to improve treatment interventions. Brain mechanisms underlying drug and food craving are suggested to be similar: for example, both are reported to be associated with increased neural activity in the orbitofrontal and anterior cingulate cortex, and a diminished regulatory influence from lateral prefrontal circuits. Several studies have begun to assess the potential benefits of brain stimulation in reducing craving and addictive behaviors. Data from a study of a one-off session of transcranial magnetic stimulation in healthy women identified as strong cravers and of individuals with bulimic-type eating disorders, reported a reduction in food craving and binge eating episodes. This provides support for a more extensive investigation of the potential therapeutic benefits of transcranial magnetic stimulation. Lastly, brain imaging studies and a dimensional approach, will improve understanding of the neural correlates of the disorders and of the mode of action of transcranial magnetic stimulation. METHODS/DESIGN: Sixty eligible obese females, with binge eating disorder, will be randomly allocated to receive 20 sessions of transcranial magnetic stimulation intervention (n = 30) or the sham transcranial magnetic stimulation intervention (n = 30) scattered 3 days/week. Thirty eligible controls will complete the baseline assessment. The primary outcome (number of binge eating episodes) will be assed at each treatment sessions, and 8 weeks after intervention completion (follow-up). It is hypothesized that mean weekly binge-eating episodes will be reduced in the intervention group, compared to the sham group, and that the effect will be maintained at follow-up. DISCUSSION: Despite the severity associated with Binge Eating Disorder, there are limited treatment options. This study is an important step in the development of more effective treatments. Importantly, the study is the first to investigating binge eating disorder using a dimensional approach, by looking at the different aspects of the disorder, such as behavioral factors, biological factors, brain circuits and chemistry. TRIAL REGISTRATION: Clinical Trials NCT02180984 . Registered in July 2014. PMID- 26265453 TI - Inhibition of porcine reproductive and respiratory syndrome virus replication in vitro using DNA-based short antisense oligonucleotides. AB - BACKGROUND: Porcine reproductive and respiratory syndrome (PRRS) is caused by porcine reproductive and respiratory syndrome virus (PRRSV) and is an economically important disease in swine-producing areas. The objective of this study was to screen for effective antisense oligonucleotides (AS-ONs) which could inhibit PRRSV replication in MARC-145 cells and in pulmonary alveolar macrophages (PAM). RESULTS: Nine short AS-ON sequences against the well-conserved regions of PRRSV (5'-UTR, NSP9, ORF5 and ORF7) were selected. When MARC-145 cells or PAM were infected with PRRSV followed by transfection with AS-ONs, four AS-ON sequences targeting 5'-UTR, ORF5 or NSP9 were found to be the most effective oligonucleotides in decreasing the cytopathic effect (CPE) induced by PRRSV infection. Quantitative PCR and indirect immunofluorescence staining confirmed that ORF7 levels were significantly reduced both at RNA and protein levels. The PRRSV titration data furthermore indicated that transfection with AS-ON YN8 could reduce the PRRSV titer by 1000-fold compared with controls. CONCLUSION: The results presented here indicate that DNA-based antisense oligonucleotides can effectively inhibit PRRSV replication in MARC-145 cells and in PAM. Furthermore, comparing with the reported hit rates (approximately 10-30 %), we achieved a higher success rate (44 %). The strategy we took to design the antisense sequences might be applied to select AS-ONs that more efficiently reduce the expression of target genes. PMID- 26265454 TI - Enhancer of zeste homolog 2 silencing inhibits tumor growth and lung metastasis in osteosarcoma. AB - The enhancer of zeste homolog 2 (EZH2) methyltransferase is the catalytic subunit of polycomb repressive complex 2 (PRC2), which acts as a transcription repressor via the trimethylation of lysine 27 of histone 3 (H3K27me3). EZH2 has been recognised as an oncogene in several types of tumors; however, its role in osteosarcoma has not been fully elucidated. Herein, we show that EZH2 silencing inhibits tumor growth and lung metastasis in osteosarcoma by facilitating re expression of the imprinting gene tumor-suppressing STF cDNA 3 (TSSC3). Our previous study showed that TSSC3 acts as a tumor suppressor in osteosarcoma. In this study, we found that EZH2 was abnormally elevated in osteosarcoma, and its overexpression was associated with poor prognosis in osteosarcoma. Silencing of EZH2 resulted in tumor growth inhibition, apoptosis and chemosensitivity enhancement. Moreover, suppression of EZH2 markedly inhibited tumor growth and lung metastasis in vivo. Furthermore, EZH2 knockdown facilitated the re expression of TSSC3 by reducing H3K27me3 in the promoter region. Cotransfection with siEZH2 and siTSSC3 could partially reverse the ability of siEZH2 alone. We have demonstrated that EZH2 plays a crucial role in tumor growth and distant metastasis in osteosarcoma; its oncogenic role is related to its regulation of the expression of TSSC3. PMID- 26265455 TI - Biodegradation of paraffin wax by crude Aspergillus enzyme preparations for potential use in removing paraffin deposits. AB - Paraffin deposition problems have plagued the oil industry. Whist mechanical and chemical methods are problematic, microbiological method of paraffin removal is considered an alternative. However, studies have mainly investigated the use of bacteria, with little attention to the potential of fungi. The performance of six Aspergillus isolates to degrade paraffin wax was evaluated under laboratory conditions using solid enzyme preparations. The results showed that all the six enzyme preparations efficiently improved the solubility of paraffin wax in n hexane and degraded n-alkanes in paraffin wax. The degradation process was accompanied by dynamic production of gases (CO2 and H2 ) and organic acids (oxalate and propionate). The shape of wax crystals markedly changed after enzymatic degradation, with a rough surface and a loose structure. This study indicates that extracellular enzymes from Aspergillus spp. can efficiently degrade paraffin wax. These enzyme preparations have the potential for use in oil wells with paraffin deposition problems. PMID- 26265456 TI - Pathological concentrations of homocysteine increases IL-1beta production in macrophages in a P2X7, NF-KB, and erk-dependent manner. AB - Elevated plasma levels of homocysteine (Hcy) are associated with the development of coronary artery disease (CAD), peripheral vascular disease, and atherosclerosis. Hyperhomocysteinemia is likely related to the enhanced production of pro-inflammatory cytokines including IL-1beta. However, the mechanisms underlying the effects of Hcy in immune cells are not completely understood. Recent studies have established a link between macrophage accumulation, cytokine IL-1beta, and the advance of vascular diseases. The purpose of the present study is to investigate the effects of Hcy on IL-1beta secretion by murine macrophages. Hcy (100 MUM) increases IL-1beta synthesis via enhancement of P2X7 expression and NF-KB and ERK activation in murine macrophages. In addition, the antioxidant agent N-acetylcysteine (NAC) reduces NF kappaB activation, ERK phosphorylation, and IL-1beta production in Hcy-exposed macrophages, indicating the importance of ROS in this pro-inflammatory process. In summary, our results show that Hcy may be involved in the synthesis and secretion of IL-1beta via NF-KB, ERK, and P2X7 stimulation in murine macrophages. PMID- 26265457 TI - Coronary Stents: The Impact of Technological Advances on Clinical Outcomes. AB - Percutaneous coronary interventions (PCI) were proposed in the late 1970s as an alternative to surgical coronary artery bypass grafting for the treatment of coronary artery disease. Important technological progress has been made since. Balloon angioplasty was replaced by bare metal stents, which allowed to permanently scaffold the coronary vessel avoiding acute recoil and abrupt occlusion. Thereafter, the introduction of early generation drug-eluting stents (DES) has significantly improved clinical outcomes, primarily by markedly reducing the risk of restenosis. New generation DES with thinner stent struts, novel durable or biodegradable polymer coatings, and new limus antiproliferative agents, have further improved upon the safety and efficacy profile of early generation DES. The present article aims to review the impact of technological advances on clinical outcomes in the field of PCI with coronary stents, and to provide a brief overview on clinical margins of improvement and unmet needs of available DES. PMID- 26265458 TI - Solid Tumor Embolotherapy in Hepatic Arteries with an Anti-reflux Catheter System. AB - Unresectable hepatoma accounts for the majority of malignant liver tumor cases for which embolization therapy is considered a viable treatment option. However, the potential risk of aberrant particle deposition in non-target regions could cause severe side-effects, alongside diminished efficacy. A computational model has been developed to analyze the particle-hemodynamics before and after deployment of an FDA-approved anti-reflux catheter. The catheter features a retractable, porous cone-like tip designed to allow forward blood flow while preventing microsphere reflux. A patient-specific hepatic artery system, with different daughter branches connected to a liver tumor, was chosen as a representative test bed. In vitro as well as in vivo measurements were used to validate the computer simulation model. The model captures the effect of tip deployment on blood perfusion and pressure drop in an interactive manner under physiologically realistic conditions. A relationship between the pressure drop and embolization level was established, which can be used to provide clinicians with real-time information on the best infusion-stop point. However, the results show that the present procedure for embolization of downstream vessels which feed a tumor is quite arbitrary. Nevertheless, a method to recycle aberrant particles captured by the deployed tip was proposed to minimize side-effects. PMID- 26265459 TI - In Situ Hydroxyapatite Content Affects the Cell Differentiation on Porous Chitosan/Hydroxyapatite Scaffolds. AB - Highly porous chitosan/hydroxyapatite composite structures with different weight ratios (100/0; 90/10; 80/20; 70/30; 60/40; 50/50; 40/60) have been prepared by precipitation method and freeze-gelation technique using calcite, urea phosphate and chitosan as starting materials. The composition of prepared composite scaffolds was characterized by X-ray diffraction analysis and Fourier transformed infrared spectroscopy, while morphology of scaffolds was imaged by scanning electron microscopy. Mercury intrusion porosimetry measurements of prepared scaffolds have shown different porosity and microstructure regarding to the HA content, along with SEM observations of scaffolds after being immersed in physiological medium. The results of swelling capacity and compressive strength measured in Dulbecco's phosphate buffer saline (DPBS) have shown higher values for composite scaffolds with lower in situ HA content. Viability, proliferation and differentiation of MC3T3-E1 cells seeded on different scaffolds have been evaluated by live dead assay and confocal scan microscopy. Our results suggest that the increase of HA content enhance osteoblast differentiation confirming osteogenic properties of highly porous CS/HA scaffolds for tissue engineering applications in bone repair. PMID- 26265461 TI - Autologous Transplantation in Elderly Multiple Myeloma Patients: Is the Procedure Cost Effective? PMID- 26265460 TI - Hydraulic Conductivity of Smooth Muscle Cell-Initiated Arterial Cocultures. AB - The purpose of the study was to examine the effects of arterial coculture conditions on the transport properties of several in vitro endothelial cell (EC) smooth muscle cell (SMC)-porous filter constructs in which SMC were grown to confluence first and then EC were inoculated. This order of culturing simulates the environment of a blood vessel wall after endothelial layer damage due to stenting, vascular grafting or other vascular wall insult. For all coculture configurations examined, we observed that hydraulic conductivity (L(p)) values were significantly higher than predicted by a resistances-in-series (RIS) model accounting for the L(p) of EC and SMC measured separately. The greatest increases were observed when EC were plated directly on top of a confluent SMC layer without an intervening filter, presumably mediated by direct EC-SMC contacts that were observed under confocal microscopy. The results are the opposite of a previous study that showed L(p) was significantly reduced compared to an RIS model when EC were grown to confluency first. The physiological, pathophysiological and tissue engineering implications of these results are discussed. PMID- 26265462 TI - The Effect of Granulocyte Colony-Stimulating Factor on Immune-Modulatory Cytokines in the Bone Marrow Microenvironment and Mesenchymal Stem Cells of Healthy Donors. AB - Granulocyte colony stimulating factor (G-CSF) is sometimes administered to donors before bone marrow (BM) harvest. G-CSF-primed (G-BM) and unprimed BM (U-BM) derived mesenchymal stem cells (MSC) were obtained from 16 healthy donors and were expanded in vitro. Their proliferative characteristics, morphology, and differentiation capacity were examined. Supernatants of the second passage of MSCs were evaluated for transforming growth factor beta1, hepatocyte growth factor, and prostaglandin E2 (PGE2) levels and compared with controls. The analyses of cytokines in the G-BM- and U-BM-derived MSCs supernatants revealed that PGE2 levels were significantly lower in the G-CSF-primed samples. These cytokines were also measured in BM plasma. The level of hepatocyte growth factor in G-BM plasma was significantly increased. The current study is the first to show the effects of G-CSF on the BM microenvironment of healthy human donors. The preliminary data suggest that G-BM- and U-BM-derived MSCs have similar morphologic/phenotypic properties and differentiation capacity but differ in their secretory capacity. Significant changes in cytokine levels of BM plasma in G-CSF-primed donors were also demonstrated. These findings suggest that BM MSCs and changes in the BM microenvironment may contribute to the effects of G-CSF on inflammation and immunomodulation. PMID- 26265463 TI - Safety and Efficacy of Combination Antiretroviral Therapy in Human Immunodeficiency Virus-Infected Adults Undergoing Autologous or Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies. AB - The ability to continue combination antiretroviral therapy (cART) in human immunodeficiency virus (HIV)-infected patients undergoing hematopoietic cell transplantation (HCT) for treatment of hematologic malignancies is likely a critical factor in preventing the establishment of an HIV reservoir in transplanted stem cells. Thus, we studied the feasibility of continued antiretroviral therapy in our HIV-infected patients undergoing autologous or allogeneic transplantation. All HIV-infected adults undergoing HCT for hematologic malignancy at Fred Hutchinson Cancer Research Center between 2006 and 2014 were included; most were enrolled in a prospective clinical study to monitor HIV reservoirs after transplantation (NCT00968630 and NCT00112593). Non nucleotide reverse transcriptase inhibitor or integrase-strand inhibitor-anchored antiretroviral therapy regimens were continued or selected before HCT by infectious disease physicians. Plasma HIV RNA was measured every other day for the first 2 weeks after transplantation and then every 2 weeks. Missed doses of cART and reasons for changing the cART regimen during the post-transplantation hospitalization were documented through review of inpatient pharmacy records. Seven autologous and 8 allogeneic transplantations were performed. In 9 transplantations, the cART regimen was not altered after HCT and no doses were missed. In 2 patients who required alterations in their cART regimen because of development of acute renal failure (n = 1) and small bowel obstruction (n = 1) after HCT, enfuvirtide was used as a bridging component of the regimen. Plasma HIV RNA remained suppressed during the first 28 days in 12 of 15 transplantations, and no patients had a plasma HIV RNA >1000 copies/mL during long-term follow up. Non-nucleotide reverse transcriptase inhibitor- and integrase-strand inhibitor-based cART are safe and effective in HIV-infected persons during the peri-HCT period. Most patients undergoing HCT were able to continue cART without missed doses. Sustained HIV viremia and emergence of resistance were not detected. PMID- 26265464 TI - Visual attraction in Drosophila larvae develops during a critical period and is modulated by crowding conditions. AB - The development of social behavior is poorly understood. Many animals adjust their behavior to environmental conditions based on a social context. Despite having relatively simple visual systems, Drosophila larvae are capable of identifying and are attracted to the movements of other larvae. Here, we show that Drosophila larval visual recognition is encoded by the movements of nearby larvae, experienced during a specific developmental critical period. Exposure to moving larvae, only during a specific period, is sufficient for later visual recognition of movement. Larvae exposed to wild-type body movements, during the critical period, are not attracted to the movements of tubby mutants, which have altered morphology. However, exposure to tubby, during the critical period, results in tubby recognition at the expense of wild-type recognition indicating that this is true learning. Visual recognition is not learned in excessively crowded conditions, and this is emulated by exposure, during the critical period, to food previously used by crowded larvae. We propose that Drosophila larvae have a distinct critical period, during which they assess both social and resource conditions, and that this irreversibly determines later visually guided social behavior. This model provides a platform towards understanding the regulation and development of social behavior. PMID- 26265465 TI - The effects of an exercise programme during pregnancy on health-related quality of life in pregnant women: a Norwegian randomised controlled trial. AB - OBJECTIVE: To investigate whether a customised exercise programme influences pregnant women's psychological wellbeing and general health perception reflecting health-related quality of life (HRQoL) in late pregnancy. DESIGN: A two-armed, two-centred randomised controlled trial. SETTING: Trondheim and Stavanger University Hospitals, Norway. POPULATION: A total of 855 healthy Caucasian pregnant women. METHODS: The intervention group was offered a 12-week exercise programme between 20 and 36 weeks of pregnancy. One weekly group session was led by physiotherapists, in addition women were encouraged to follow a home exercise programme at least twice a week. The exercise programme followed standard recommendations and included both aerobic and strength training. The control group received regular antenatal care. Pretests and post-tests were performed at 18-22 and 32-36 weeks of pregnancy. MAIN OUTCOME MEASURES: In the original study primary outcome was gestational diabetes mellitus, but in this report the primary outcome is HRQoL. The questionnaire Psychological General Wellbeing Index (PGWBI) was used to assess psychological wellbeing and self-perceived general health before and after the intervention. PGWBI contains six subscales and it is also possible to summarise all items to a global score. RESULTS: No association between antenatal exercise programme allocation and PGWBI (global score and subscales) was found. The study population was homogeneous and had high educational level. CONCLUSIONS: The results indicate that offering women an exercise programme during pregnancy does not seem to influence healthy pregnant women's psychological wellbeing and self-perceived general health. Further research is needed to investigate the effects of exercise in pregnancy on psychological wellbeing and self-perceived general health among women from different sociocultural subgroups. TWEETABLE ABSTRACT: Exercise in pregnancy does not influence healthy pregnant women's health-related quality of life. PMID- 26265466 TI - Granulomatous slack skin-like clinical findings in Sezary syndrome. AB - Granulomatous slack skin (GSS) is a very rare condition that has been described as a variant of mycosis fungoides. It is characterized by the development of bulky and pendulous skin folds in flexural areas that are histologically formed by atypical T lymphocytes, histiocytes and giant cells. We report the case of a 37-year-old African-American female with history of Sezary syndrome (SS) that while on treatment for the disease and in a space of 1 month developed exorbitant slack folds in the axillae and cervical area mimicking GSS. The absence of giant cells and epithelioid granulomas in the biopsy ruled out this diagnosis. We report this peculiar SS presentation that clinically resembles GSS, but with histopathology that does not show the typical features of this condition. We also review the literature in regard to SS, GSS and granulomatous mycosis fungoides (GMF), particularly the existing criteria to differentiate these various entities. PMID- 26265467 TI - Elicitation effect of Saccharomyces cerevisiae yeast extract on main health promoting compounds and antioxidant and anti-inflammatory potential of butter lettuce (Lactuca sativa L.). AB - BACKGROUND: This paper presents a study on changes in the main phytochemical levels and antioxidant and anti-inflammatory activity of lettuce caused by different doses and times of application of yeast extracts. RESULTS: Elicitation with yeast extract caused an increase in the total phenolic compounds and chlorophyll content, which varied according to the dose and time of spraying, but it did not have a positive impact on vitamin C, flavonoid and carotenoid content in lettuce. The best effect was achieved by double spraying with 1% yeast extract and by single spraying with 0.1% yeast extract. The increase in phytochemical content was positively correlated with the antioxidant and anti-inflammatory activity of the studied lettuce leaves. Chicoric acid seems to be the major contributor to these antioxidant activities. CONCLUSION: Yeast extract may be used as a natural, environmentally friendly and safe elicitor for improving the health-promoting qualities of lettuce. (c) 2015 Society of Chemical Industry. PMID- 26265468 TI - Connexin Type and Fluorescent Protein Fusion Tag Determine Structural Stability of Gap Junction Plaques. AB - Gap junctions (GJs) are made up of plaques of laterally clustered intercellular channels and the membranes in which the channels are embedded. Arrangement of channels within a plaque determines subcellular distribution of connexin binding partners and sites of intercellular signaling. Here, we report the discovery that some connexin types form plaque structures with strikingly different degrees of fluidity in the arrangement of the GJ channel subcomponents of the GJ plaque. We uncovered this property of GJs by applying fluorescence recovery after photobleaching to GJs formed from connexins fused with fluorescent protein tags. We found that connexin 26 (Cx26) and Cx30 GJs readily diffuse within the plaque structures, whereas Cx43 GJs remain persistently immobile for more than 2 min after bleaching. The cytoplasmic C terminus of Cx43 was required for stability of Cx43 plaque arrangement. We provide evidence that these qualitative differences in GJ arrangement stability reflect endogenous characteristics, with the caveat that the sizes of the GJs examined were necessarily large for these measurements. We also uncovered an unrecognized effect of non-monomerized fluorescent protein on the dynamically arranged GJs and the organization of plaques composed of multiple connexin types. Together, these findings redefine our understanding of the GJ plaque structure and should be considered in future studies using fluorescent protein tags to probe dynamics of highly ordered protein complexes. PMID- 26265469 TI - Bacterial rotary export ATPases are allosterically regulated by the nucleotide second messenger cyclic-di-GMP. AB - The widespread second messenger molecule cyclic di-GMP (cdG) regulates the transition from motile and virulent lifestyles to sessile, biofilm-forming ones in a wide range of bacteria. Many pathogenic and commensal bacterial-host interactions are known to be controlled by cdG signaling. Although the biochemistry of cyclic dinucleotide metabolism is well understood, much remains to be discovered about the downstream signaling pathways that induce bacterial responses upon cdG binding. As part of our ongoing research into the role of cdG signaling in plant-associated Pseudomonas species, we carried out an affinity capture screen for cdG binding proteins in the model organism Pseudomonas fluorescens SBW25. The flagella export AAA+ ATPase FliI was identified as a result of this screen and subsequently shown to bind specifically to the cdG molecule, with a KD in the low micromolar range. The interaction between FliI and cdG appears to be very widespread. In addition to FliI homologs from diverse bacterial species, high affinity binding was also observed for the type III secretion system homolog HrcN and the type VI ATPase ClpB2. The addition of cdG was shown to inhibit FliI and HrcN ATPase activity in vitro. Finally, a combination of site-specific mutagenesis, mass spectrometry, and in silico analysis was used to predict that cdG binds to FliI in a pocket of highly conserved residues at the interface between two FliI subunits. Our results suggest a novel, fundamental role for cdG in controlling the function of multiple important bacterial export pathways, through direct allosteric control of export ATPase proteins. PMID- 26265471 TI - Using NHS data on statin outcomes. PMID- 26265470 TI - Amino Acid Proximities in Two Sup35 Prion Strains Revealed by Chemical Cross linking. AB - Strains of the yeast prion [PSI] are different folding patterns of the same Sup35 protein, which stacks up periodically to form a prion fiber. Chemical cross linking is employed here to probe different fiber structures assembled with a mutant Sup35 fragment. The photo-reactive cross-linker, p-benzoyl-l-phenylalanine (pBpa), was biosynthetically incorporated into bacterially prepared recombinant Sup(1-61)-GFP, containing the first 61 residues of Sup35, followed by the green fluorescent protein. Four methionine substitutions and two alanine substitutions were introduced at fixed positions in Sup(1-61) to allow cyanogen bromide cleavage to facilitate subsequent mass spectrometry analysis. Amyloid fibers of pBpa and Met/Ala-substituted Sup(1-61)-GFP were nucleated from purified yeast prion particles of two different strains, namely VK and VL, and shown to faithfully transmit specific strain characteristics to yeast expressing the wild type Sup35 protein. Intra- and intermolecular cross-linking were distinguished by tandem mass spectrometry analysis on fibers seeded from solutions containing equal amounts of (14)N- and (15)N-labeled protein. Fibers propagating the VL strain type exhibited intra- and intermolecular cross-linking between amino acid residues 3 and 28, as well as intra- and intermolecular linking between 32 and 55. Inter- and intramolecular cross-linking between residues 32 and 55 were detected in fibers propagating the VK strain type. Adjacencies of amino acid residues in space revealed by cross-linking were used to constrain possible chain folds of different [PSI] strains. PMID- 26265472 TI - The zebrafish miR-462/miR-731 cluster is induced under hypoxic stress via hypoxia inducible factor 1alpha and functions in cellular adaptations. AB - Hypoxia, a unique and essential environmental stress, evokes highly coordinated cellular responses, and hypoxia-inducible factor (HIF) 1 in the hypoxia signaling pathway, an evolutionarily conserved cellular signaling pathway, acts as a master regulator of the transcriptional response to hypoxic stress. MicroRNAs (miRNAs), a major class of posttranscriptional gene expression regulators, also play pivotal roles in orchestrating hypoxia-mediated cellular adaptations. Here, global miRNA expression profiling and quantitative real-time PCR indicated that the up-regulation of the miR-462/miR-731 cluster in zebrafish larvae is induced by hypoxia. It was further validated that miR-462 and miR-731 are up-regulated in a Hif-1alpha-mediated manner under hypoxia and specifically target ddx5 and ppm1da, respectively. Overexpression of miR-462 and miR-731 represses cell proliferation through blocking cell cycle progress of DNA replication, and induces apoptosis. In situ detection revealed that the miR-462/miR-731 cluster is highly expressed in a consistent and ubiquitous manner throughout the early developmental stages. Additionally, the transcripts become restricted to the notochord, pharyngeal arch, liver, and gut regions from postfertilization d 3 to 5. These data highlight a previously unidentified role of the miR-462/miR-731 cluster as a crucial signaling mediator for hypoxia-mediated cellular adaptations and provide some insights into the potential function of the cluster during embryonic development. PMID- 26265474 TI - Evolving trends in cerebral amyloid angiopathy research themes: insights from medical subject heading analysis. PMID- 26265475 TI - Residential mobility and risk of major depressive episode among adolescents in the National Survey on Drug Use and Health. AB - BACKGROUND: Prior research identified associations between residential moves during adolescence and depression, but studies used small or nonrepresentative samples. The aim of this study was to examine the associations between residential moves and major depressive episode (MDE) in a large, nationally representative sample of adolescents in the USA. METHODS: This study analyzed data on 139 606 adolescents (12-17 years old) from the National Survey on Drug Use and Health, an annual cross-sectional survey from 2005 to 2012. We analyzed data on MDE prevalence within the past 12 months and residential moves within the past 5 years, using multivariable logistic regression models to control for observable covariates. RESULTS: Adolescents who moved at least once in the past 5 years had 35% higher odds of MDE than those who did not (odds ratio, 1.35; 95% confidence interval, 1.28-1.43), with odds of MDE increasing as the number of moves increased. Associations were particularly strong among younger and higher income adolescents. CONCLUSION: Findings suggest that adolescents who move often may be a vulnerable group in need of mental health screening and services. Next steps in research include longitudinal studies with data on preexisting mental health issues and childhood adverse events. PMID- 26265473 TI - Dissociations of spatial congruence effects across response measures: an examination of delta plots. AB - Spatial congruence ("Simon") effects on reaction time (RT) and response force (RF) were studied in two experiments requiring speeded choice responses to the color of a stimulus located irrelevantly to the left or right of fixation. In Experiment 1 with unimanual responses, both RT and incorrect-hand RF were sensitive to spatial congruence, and both showed larger Simon effects following a congruent trial than following an incongruent one. RT and incorrect-hand RF were dissociated in distributional (i.e., delta plot) analyses, however. As in previous studies, the Simon effect on RT was largest for the fastest responses and diminished as RT increased (i.e., decreasing delta plot). In contrast, Simon effects on RF did not decrease for slower responses; if anything, they increased slightly. In Experiment 2 participants made bimanual responses, allowing measurement of the spatial congruence effect for each trial. Responses were both faster and more forceful with the spatially congruent hand than with the spatially incongruent one, but neither of these effects decreased for slower responses. Overall, the results demonstrate that at least some motor-level effects of irrelevant spatial location persist for slower responses. PMID- 26265476 TI - Evaluation of recruitment and selection for specialty training in public health: interim results of a prospective cohort study to measure the predictive validity of the selection process. AB - BACKGROUND: The recruitment process for public health specialty training includes an assessment centre (AC) with three components, Rust Advanced Numerical Reasoning Appraisal (RANRA), Watson-Glaser Critical Thinking Appraisal (WGCT) and a Situation Judgement Test (SJT), which determines invitation to a selection centre (SC). The scores are combined into a total recruitment (TR) score that determines the offers of appointment. METHODS: A prospective cohort study using anonymous record linkage to investigate the association between applicant's scores in the recruitment process and registrar's progress through training measured by results of Membership Faculty Public Health (MFPH) examinations and outcomes of the Annual Review of Competence Progression (ARCP). RESULTS: Higher scores in RANRA, WGCT, AC, SC and TR were all significantly associated with higher adjusted odds of passing Part A MFPH exam at the first attempt. Higher scores in AC, SC and TR were significantly associated with passing Part B exam at the first attempt. Higher scores in SJT, AC and SC were significantly associated with satisfactory ARCP outcomes. CONCLUSIONS: The current UK national recruitment and selection process for public health specialty training has good predictive validity. The individual components of the process are testing different skills and abilities and together they are providing additive value. PMID- 26265477 TI - Increase in socioeconomic inequalities in mortality in a Southern European region: a small-area ecological study. AB - BACKGROUND: This study sought to describe the total mortality trend by socioeconomic deprivation (SED) in the Madrid Autonomous Region, by sex and age group. METHODS: Cross-sectional ecological study by census tract, in two periods: 1994-2000 (P1) with SED of 1996 census and 2001-07 (P2) with SED of 2001 census. We calculated the relative risks (RRs) and their 95% credibility intervals (95% CIs) by SED quintile (Q), taking the quintile of least deprivation as reference. Besag-York-Mollie ecological regression models and the Integrated Nested Laplace Approximation procedure were applied. The absolute differences in age standardized rates were compared by SED quintile. RESULTS: Inequalities decreased in young adults: among men aged 20-39 years, the RR in Q5 versus Q1 ranged from 2.73 (95% CI, 2.51-3.02) in P1 to 1.93 (95% CI, 1.76-2.15) in P2, due to the greater improvement in the most underprivileged groups. In contrast, there was an increase in SED-related mortality in the 40-79 age group. Among men aged 40-59 years, the RR in Q5 versus Q1 rose from 1.88 (95% CI, 1.76-2.02) in P1 to 2.29 (95% CI, 2.17-2.43) in P2; the improvement was greater in the most privileged groups. CONCLUSION: In a context of an economic boom, inequalities were observed to increase among adults by a greater improvement in the most privileged groups. PMID- 26265478 TI - Non-invasive imaging in assessment of the asymptomatic diabetic patient: Is it of value? PMID- 26265480 TI - Evaluation of an educational website for parents of children with ADHD. AB - INTRODUCTION: ADHD is a relatively common neuro-developmental condition characterized by hyperactivity, impulsivity and inattention. The provision of timely and accurate information about the condition and about strategies to manage it is vital especially because of widespread misconceptions about it. AIM: To see the effect of an educational website on (i) parental perceptions (ii) knowledge levels, and to obtain feedback to optimise user-experience. METHOD: Parents whose children had ADHD (or were close to diagnosis) were recruited. Following a 30-item baseline knowledge test parents/carers were directed to an educational website on ADHD. After this they were re-contacted for follow up testing and feedback. RESULTS: n=172, 14 were lost to follow up. Ninety-one (59.4 %) participants were known to have accessed the website at follow up. The majority of carers accessed the website just once or twice (32.7%). Of those who did not access the website 65% cited a lack of time as the reason while 29% cited they were unable to access the internet at the time. The majority (74%) of those accessing the site were just browsing for general information. Parents showed increased knowledge post website use p=0.000. Of those accessing the website the majority (85.5%) felt it was relevant to them and would use it again (90.8%). Content analysis of open-ended feedback identified eight core themes including website appearance, content, functionality, perceptions, target audience, usability, usage patterns with areas for improvement noted in four areas. CONCLUSION: Websites can be used as an adjunct to information given at clinic. Although a majority of parents will access them, there are still barriers to access e.g. time. Websites do seem to improve parent/carer knowledge levels. PMID- 26265479 TI - Efficacy and safety of inhaled calcium lactate PUR118 in the ozone challenge model--a clinical trial. AB - BACKGROUND: The ozone challenge model can be used to assess the efficacy of anti inflammatory compounds in early phases of clinical drug development. PUR118, a calcium salt based formulation engineered in the iSPERSE(TM) dry powder delivery technology, is a novel anti-inflammatory drug for COPD. Here we evaluated the efficacy and safety of three doses of PUR118 in attenuating ozone-induced airway inflammation in healthy volunteers. METHODS: In a single-blind, phase 1B proof of concept study, 24 subjects were enrolled to sequentially receive three doses of PUR118 (5.5 mg, n = 18; 11.0 mg, n = 18; 2.8 mg, n = 16). Each dose was inhaled 3 times (1, 13, 25 h, preceded by 2 puffs salbutamol) before the ozone exposure (250 ppb, 3 h intermittent exercise). Sputum was induced 3 h after the end of exposure. RESULTS: Sputum neutrophils, sputum CD14+ cells, as well as concentrations of IL1B, IL6, IL8, MMP9, and TNFA in sputum supernatant significantly increased after ozone exposure (n = 24). The percentage of sputum neutrophils (n = 12 who completed all treatments) did not change following treatment with different doses of PUR118. The high dose treatment group (n = 16) showed a decrease in the percentage and number of sputum macrophages (p <= 0.05) as well as a decrease in blood neutrophils (p = 0.04), and an increase in blood CD14 + cells (p = 0.04) compared to baseline. All dosages of PUR118 were safe and well tolerated. CONCLUSION: Ozone challenge resulted in the expected and significant increase of sputum inflammatory parameters. Treatment with multiple rising doses of PUR118 was safe and three applications within 25 h prior to the ozone challenge had small effects on ozone-induced airway inflammation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01690949. Registered 12 September 2012. PMID- 26265481 TI - Changepoint detection in base-resolution methylome data reveals a robust signature of methylated domain landscape. AB - BACKGROUND: Base-resolution methylome data generated by whole-genome bisulfite sequencing (WGBS) is often used to segment the genome into domains with distinct methylation levels. However, most segmentation methods include many parameters to be carefully tuned and/or fail to exploit the unsurpassed resolution of the data. Furthermore, there is no simple method that displays the composition of the domains to grasp global trends in each methylome. RESULTS: We propose to use changepoint detection for domain demarcation based on base-resolution methylome data. While the proposed method segments the methylome in a largely comparable manner to conventional approaches, it has only a single parameter to be tuned. Furthermore, it fully exploits the base-resolution of the data to enable simultaneous detection of methylation changes in even contrasting size ranges, such as focal hypermethylation and global hypomethylation in cancer methylomes. We also propose a simple plot termed methylated domain landscape (MDL) that globally displays the size, the methylation level and the number of the domains thus defined, thereby enabling one to intuitively grasp trends in each methylome. Since the pattern of MDL often reflects cell lineages and is largely unaffected by data size, it can serve as a novel signature of methylome. CONCLUSIONS: Changepoint detection in base-resolution methylome data followed by MDL plotting provides a novel method for methylome characterization and will facilitate global comparison among various WGBS data differing in size and even species origin. PMID- 26265482 TI - Facility Mammography Volume in Relation to Breast Cancer Screening Outcomes. AB - OBJECTIVES: To clarify the relationship between facility-level mammography interpretive volume and breast cancer screening outcomes. METHODS: We calculated annual mammography interpretive volumes from 2000-2009 for 116 facilities participating in the U.S. Breast Cancer Surveillance Consortium (BCSC). Radiology, pathology, cancer registry, and women's self-report information were used to determine the indication for each exam, cancer characteristics, and patient characteristics. We examined the effect of annual total volume and percentage of mammograms that were screening on cancer detection rates using multinomial logistic regression adjusting for age, race/ethnicity, time since last mammogram, and BCSC registries. "Good prognosis" tumours were defined as screen-detected invasive cancers that were <15 mm, early stage, and lymph node negative at diagnosis. RESULTS: From 3,098,481 screening mammograms, 9,899 cancers were screen-detected within one year of the exam. Approximately 80% of facilities had annual total interpretive volumes of >2,000 mammograms, and 42% had >5,000. Higher total volume facilities were significantly more likely to diagnose invasive tumours with good prognoses (odds ratio [OR] 1.32; 95% confidence interval [CI] 1.10-1.60, for total volume of 5,000-10,000/year v. 1,000-2,000/year; p-for-trend <0.001). A concomitant decrease in tumours with poor prognosis was seen (OR 0.78; 95%CI 0.63-0.98 for total volume of 5,000 10,000/year v. 1,000-2,000/year). CONCLUSIONS: Mammography facilities with higher total interpretive volumes detected more good prognosis invasive tumours and fewer poor prognosis invasive tumours, suggesting that women attending these facilities may be more likely to benefit from screening. PMID- 26265483 TI - Treatment with high dose of erythropoiesis-stimulating agents and mortality: analysis with a sequential Cox approach and a marginal structural model. AB - BACKGROUND: Anemia-correction trials indicated higher mortality rates in chronic kidney disease patients assigned to higher hemoglobin targets. The safety of the high erythropoiesis-stimulating agent (ESA) doses that these patients received has therefore been questioned. However, no trial that directly compares treatment with different ESA doses has been published. We thus aimed to estimate the effect of high ESA dose on mortality in an observational cohort of dialysis patients. METHODS: The Netherlands Cooperative Study on the Adequacy of Dialysis is a Dutch cohort study of incident dialysis patients in which ESA dose, comorbidities, and laboratory parameters were collected every 6 months. Mortality in patients with a high ESA dose (above median 6000 units/week) was compared with that in patients with no or low ESA dose with Cox regression analyses. To handle time-dependent confounding, a sequential Cox approach was used conditional on baseline covariates, with inverse probability of censoring weights (IPCW) for dependent censoring. Analyses were repeated with a marginal structural model (MSM) with inverse probability of treatment weights and IPCW. RESULTS: Hazard ratio (HR) for high ESA dose was 1.20 (95%CI 0.83-1.73) with a sequential Cox and 1.54 (95%CI 1.08-2.18) with an MSM. Truncation of weights in the MSM did not affect estimates. To compare, conventional Cox analyses indicated a baseline adjusted HR of 1.66 (95%CI 1.20-2.31). CONCLUSION: Patients treated with high ESA dose have a 1.2-1.5 increased risk of mortality. Our analyses support guidelines advising a conservative ESA dosing regimen, which carefully weighs the patients' benefits and risks. PMID- 26265484 TI - Equilibrium-phase MR angiography: Comparison of unspecific extracellular and protein-binding gadolinium-based contrast media with respect to image quality. AB - The purpose of this study was to compare contrast and image quality of whole-body equilibrium-phase high-spatial-resolution MR angiography using a non-protein binding unspecific extracellular gadolinium-based contrast medium with that of two contrast media with different protein-binding properties. 45 patients were examined using either 15 mL of gadobutrol (non-protein-binding, n = 15), 32 mL of gadobenate dimeglumine (weakly protein binding, n = 15) or 11 mL gadofosveset trisodium (protein binding, n = 15) followed by equilibrium-phase high-spatial resolution MR-angiography of four consecutive anatomic regions. The time elapsed between the contrast injection and the beginning of the equilibrium-phase image acquisition in the respective region was measured and was up to 21 min. Signal intensity was measured in two vessels per region and in muscle tissue. Relative contrast (RC) values were calculated. Vessel contrast, artifacts and image quality were rated by two radiologists in consensus on a five-point scale. Compared with gadobutrol, gadofosveset trisodium revealed significantly higher RC values only when acquired later than 15 min after bolus injection. Otherwise, no significant differences between the three contrast media were found regarding vascular contrast and image quality. Equilibrium-phase high-spatial-resolution MR angiography using a weakly protein-binding or even non-protein-binding contrast medium is equivalent to using a stronger protein-binding contrast medium when image acquisition is within the first 15 min after contrast injection, and allows depiction of the vasculature with high contrast and image quality. The protein binding contrast medium was superior for imaging only later than 15 min after contrast medium injection. PMID- 26265486 TI - Gas-phase dynamics in graphene growth by chemical vapour deposition. AB - Chemical vapour deposition on a Cu substrate is becoming a very important approach to obtain high quality graphene samples. Previous studies of graphene growth on Cu mainly focus on surface processes. However, recent experiments suggest that gas-phase dynamics also plays an important role in graphene growth. In this article, gas-phase processes are systematically studied using computational fluid dynamics. Our simulations clearly show that graphene growth is limited by mass transport under ambient pressures while it is limited by surface reactions under low pressures. The carbon deposition rate at different positions in the tube furnace and the concentration of different gas phase species are calculated. Our results confirm that the previously realized graphene thickness control by changing the position of the Cu foil is a result of gas phase methane decomposition reactions. PMID- 26265485 TI - Food Shortage Causes Differential Effects on Body Composition and Tissue-Specific Gene Expression in Salmon Modified for Increased Growth Hormone Production. AB - Growth hormone (GH) transgenic salmon possesses markedly increased metabolic rate, appetite, and feed conversion efficiency, as well as an increased ability to compete for food resources. Thus, the ability of GH-transgenic fish to withstand periods of food deprivation as occurs in nature is potentially different than that of nontransgenic fish. However, the physiological and genetic effects of transgenic GH production over long periods of food deprivation remain largely unknown. Here, GH-transgenic coho salmon (Oncorhynchus kisutch) and nontransgenic, wild-type coho salmon were subjected to a 3-month food deprivation trial, during which time performance characteristics related to growth were measured along with proximate compositions. To examine potential genetic effects of GH-transgenesis on long-term food deprivation, a group of genes related to muscle development and liver metabolism was selected for quantitative PCR analysis. Results showed that GH-transgenic fish lose weight at an increased rate compared to wild-type even though proximate compositions remained relatively similar between the groups. A total of nine genes related to muscle physiology (cathepsin, cee, insulin-like growth factor, myostatin, murf-1, myosin, myogenin, proteasome delta, tumor necrosis factor) and five genes related to liver metabolism (carnitine palmitoyltransferase, fatty acid synthase, glucose-6 phosphatase, glucose-6-phosphate dehydrogenase, glucokinase) were shown to be differentially regulated between GH-transgenic and wild-type coho salmon over time. These genetic and physiological responses assist in identifying differences between GH-transgenic and wild-type salmon in relation to fitness effects arising from elevated growth hormone during periods of long-term food shortage. PMID- 26265487 TI - Ability of older people with dementia or cognitive impairment to manage medicine regimens: a narrative review. AB - Impaired cognition has a significant impact on a person's ability to manage their medicines. The aim of this paper is to provide a narrative review of contemporary literature on medicines management by people with dementia or cognitive impairment living in the community, methods for assessing their capacity to safely manage medicines, and strategies for supporting independent medicines management. Studies and reviews addressing medicines management by people with dementia or cognitive impairment published between 2003 and 2013 were identified via searches of Medline and other databases. The literature indicates that as cognitive impairment progresses, the ability to plan, organise, and execute medicine management tasks is impaired, leading to increased risk of unintentional non-adherence, medication errors, preventable medication-related hospital admissions and dependence on family carers or community nursing services to assist with medicines management. Impaired functional capacity may not be detected by health professionals in routine clinical encounters. Assessment of patients' (or carers') ability to safely manage medicines is not undertaken routinely, and when it is there is variability in the methods used. Self-report and informant report may be helpful, but can be unreliable or prone to bias. Measures of cognitive function are useful, but may lack sensitivity and specificity. Direct observation, using a structured, standardised performance based tool, may help to determine whether a person is able to manage their medicines and identify barriers to adherence such as inability to open medicine packaging. A range of strategies have been used to support independent medicines management in people with cognitive impairment, but there is little high-quality research underpinning these strategies. Further studies are needed to develop and evaluate approaches to facilitate safe medicines management by older people with cognitive impairment and their carers. PMID- 26265488 TI - The taphonomy of blood components in decomposing bone and its relevance to physical anthropology. AB - OBJECTIVES: The variation and persistence of blood components, in particular red blood cells (RBCs), within bone tissue during the decomposition process, especially at the early stages and in different taphonomic conditions, has never been thoroughly investigated, regardless of the fact that knowing how blood survives or degrades within bone could be of help in solving many anthropological issues, such as trauma analysis and interpretation. MATERIALS AND METHODS: This research investigated the influence of time and taphonomy on the persistence and detectability of blood components in parietal bone fragments (of different post mortem periods and taphonomic conditions) through histological (Hematoxilin and Eosin, HE) and immunohistochemical (Glycophorin A, GYPA) analyses. RESULTS: The immunohistochemical investigation for GYPA showed the presence of RBCs under the form of erythrocyte debris or residues otherwise morphologically unidentifiable using only HE staining. Hence, while well-defined RBCs can be observed only in the first week of decomposition, afterward these structures can be detectable with certainty only by immunohistochemical analysis, which reveals discrete quantities of RBC residues also in dry bone (post mortem interval, or PMI, of 15 years), but not in archaeological samples, in which the greater PMI and the different taphonomic conditions together could be the answer behind such difference. DISCUSSION: This study highlights the usefulness and potential of immunohistochemical detection of GYPA in RBC investigation and gives a realistic idea of the persistence and detectability of erythrocytes in different osteological taphonomic conditions, in contrast to results reported by some authors in literature. Another important result concerns the detection of RBC residues in dry bone, which opens the way to the possible use of RBCs in trauma interpretation. PMID- 26265489 TI - Evaluation of the Kots'iihtla ("We Light the Fire") Project: building resiliency and connections through strengths-based creative arts programming for Indigenous youth. AB - BACKGROUND: The creative arts - music, film, visual arts, dance, theatre, spoken word, literature, among others - are gradually being recognised as effective health promotion tools to empower, engage and improve the health and well-being in Indigenous youth communities. Arts-based programming has also had positive impacts in promoting health, mental wellness and resiliency amongst youth. However, often times the impacts and successes of such programming are not formally reported on, as reflected by the paucity of evaluations and reports in the literature. OBJECTIVE: The objective of this study was to evaluate a creative arts workshop for Tlicho youth where youth explored critical community issues and found solutions together using the arts. We sought to identify the workshop's areas of success and challenge. Ultimately, our goal is to develop a community led, youth-driven model to strengthen resiliency through youth engagement in the arts in circumpolar regions. DESIGN: Using a mixed-methods approach, we conducted observational field notes, focus groups, questionnaires, and reflective practice to evaluate the workshop. Four youth and five facilitators participated in this process overall. RESULTS: Youth reported gaining confidence and new skills, both artistic and personal. Many youth found the workshop to be engaging, enjoyable and culturally relevant. Youth expressed an interest in continuing their involvement with the arts and spreading their messages through art to other youth and others in their communities. CONCLUSIONS: Engagement and participation in the arts have the potential to build resiliency, form relationships, and stimulate discussions for community change amongst youth living in the North. PMID- 26265490 TI - First report outside Eastern Europe of West Nile virus lineage 2 related to the Volgograd 2007 strain, northeastern Italy, 2014. AB - BACKGROUND: West Nile virus (WNV) is a Flavivirus transmitted to vertebrate hosts by mosquitoes, maintained in nature through an enzootic bird-mosquito cycle. In Europe the virus became of major public health and veterinary concern in the 1990s. In Italy, WNV re-emerged in 2008, ten years after the previous outbreak and is currently endemic in many areas of the country. In particular, the northeastern part of Italy experience continuous viral circulation, with human outbreaks caused by different genovariants of WNV lineage 1, Western-European and Mediterranean subcluster, and WNV lineage 2, Hungarian clade. Alongside the WNV National Surveillance Program that has been in place since 2002, regional surveillance plans were implemented after 2008 targeting mosquitoes, animals and humans. FINDINGS: In July and September 2014, West Nile virus lineage 2 was detected in pools of Culex pipiens s.l. mosquitoes from northeastern Italy. Whole genome sequencing and phylogenetic analysis of two representative samples identified the presence of WNV lineage 2 related to the Volgograd 2007 strain (99.3 % nucleotide sequence identity), in addition to WNV lineage 2 Hungarian clade. CONCLUSIONS: This is the first evidence of the circulation of a WNV lineage 2 strain closely related to the Volgograd 2007 outside Eastern Europe, where it has caused large human outbreaks. This strain may pose a new threat to animal and human health in Italy. PMID- 26265491 TI - Thirty years of artificial intelligence in medicine (AIME) conferences: A review of research themes. AB - BACKGROUND: Over the past 30 years, the international conference on Artificial Intelligence in MEdicine (AIME) has been organized at different venues across Europe every 2 years, establishing a forum for scientific exchange and creating an active research community. The Artificial Intelligence in Medicine journal has published theme issues with extended versions of selected AIME papers since 1998. OBJECTIVES: To review the history of AIME conferences, investigate its impact on the wider research field, and identify challenges for its future. METHODS: We analyzed a total of 122 session titles to create a taxonomy of research themes and topics. We classified all 734 AIME conference papers published between 1985 and 2013 with this taxonomy. We also analyzed the citations to these conference papers and to 55 special issue papers. RESULTS: We identified 30 research topics across 12 themes. AIME was dominated by knowledge engineering research in its first decade, while machine learning and data mining prevailed thereafter. Together these two themes have contributed about 51% of all papers. There have been eight AIME papers that were cited at least 10 times per year since their publication. CONCLUSIONS: There has been a major shift from knowledge-based to data-driven methods while the interest for other research themes such as uncertainty management, image and signal processing, and natural language processing has been stable since the early 1990s. AIME papers relating to guidelines and protocols are among the most highly cited. PMID- 26265492 TI - Electro-acupuncture improves the social interaction behavior of rats. AB - Oxytocin (OXT) and arginine-vasopressin (AVP) are two closely related neuropeptides and implicated in the regulation of mammalian social behaviors. A prior clinical study in our laboratory suggested that electro-acupuncture (EA) alleviated social impairment in autistic children accompanied by changes of peripheral levels of OXT and AVP. However, it remains unclear whether EA stimulation had an impact on central OXT and AVP levels. In the present study, rats were subjected to a single session of EA (sEA) or repeated sessions of EA (rEA). Following the stimulation, mRNA levels and peptide levels of OXT/AVP systems were determined. The results showed that sEA led to region-specific up regulation of OXT and AVP mRNA levels in the hypothalamus where the peptides were produced, without affecting the content of OXT and AVP in the hypothalamus and peripheral blood. The rEA of 5 sessions in 9 days was given to the low socially interacting (LSI) rats. LSI rats that underwent rEA showed significant improvement of social behavior characterized by spending more time investigating the strange rats in the three-chamber sociability test. The improved sociability was accompanied by an up-regulation of mRNA and the peptide levels of OXT or AVP in SON of the hypothalamus as well as a significant increase of the serum level of AVP. It is concluded that activation of OXT/AVP systems may be associated with the pro-social effect caused by EA stimulation. PMID- 26265493 TI - Investigation of gender difference in human response to temperature step changes. AB - The purpose of this study was to examine gender difference in human response to temperature step changes. A total of three step-change conditions (S5: 32 degrees C-37 degrees C-32 degrees C, S11: 26 degrees C-37 degrees C-26 degrees C, and S15: 22 degrees C-37 degrees C-22 degrees C) were designed and a laboratory experiment with 12 males and 12 females was performed. Results of this study support our hypothesis that females differ from males in human response to sudden temperature changes from the perspectives of psychology, physiology and biomarkers. Females are more prone to show thermal dissatisfaction to cool environments while males are more likely to feel thermal discomfort in warm environments. It is logical that men have a stronger thermoregulation ability than women as male skin temperature change amplitude is smaller while the time to be stable for skin temperature is shorter than that of females after both up-steps and down-steps. In S15, males witnessed a more intensive decrease in RMSSD while females underwent a remarkable instant reduce in oral temperatures after the up-step. Marginal significance was observed in male IL-6 before and after the up-step in S15 while female IL-6 prominently increased after the down step in S15. PMID- 26265494 TI - Role of the heterojunctions in In2O3-composite SnO2 nanorod sensors and their remarkable gas-sensing performance for NO(x) at room temperature. AB - Establishing heterostructures, as a good strategy to improve gas sensing performance, has been studied extensively. In this research, In2O3-composite SnO2 nanorod (ICTOs) heterostructures have been prepared via electrospinning, followed by calcination. It is found that In2O3 can improve the carrier density and oxygen deficiency of SnO2. In particular, the 3ICTO (Sn : In atom ratio of 25 : 0.3) nanorods with special particle distributions show an excellent sensing response towards different concentrations of NOx at room temperature. The highest sensing response is up to 8.98 for 100 ppm NOx with a fast response time of 4.67 s, which is over 11 times higher than that of pristine SnO2 nanorods at room temperature and the lowest detection limit is down to 0.1 ppm. More significantly, it presents good stability after 30 days for NOx of low concentration (0.1 ppm and 0.5 ppm). In addition, the rational band structure model combined with the surface depletion model which describe the NOx gas sensing mechanism of 3ICTO are presented. The 3ICTO nanorods may be promising in the application of gas sensors. PMID- 26265495 TI - Protective efficacy of Nigella sativa seeds and oil against columnaris disease in fishes. AB - Columnaris disease, caused by the bacterium Flavobacterium columnare, is currently the most frequently reported bacterial disease affecting farm-raised channel catfish in the USA. Common treatments against the disease include the use of medicated feed that has led to emergent antibiotic resistant strains of F. columnare. Nigella sativa (Black cumin) is a medicinal herb commonly used by many cultures as a natural remedy for numerous disorders. Recently, we have discovered the antibacterial activity of N. sativa and its oil extract against F. columnare. In this study, we showed N. sativa oil (NSO) strongly inhibited the growth of all of the strains of F. columnare tested and yielded significantly larger zones of inhibition than those produced by oxytetracyclin. We tested the protective effect against columnaris disease in vivo by incorporating NSO (5%) or N. sativa seeds (NSS) (5%) into fish feeds. Fishes (Ictalurus punctatus and Danio rerio) fed amended diets displayed significantly lower mortality than those fed control diets. Per cent mortalities in control groups ranged from 77% to 44% and from 70% to 18% in zebrafish and channel catfish, respectively. A dose study using different NSS concentrations showed that 5% NSS offered the most protection against columnaris disease in channel catfish. PMID- 26265496 TI - The Critical Role of the Staff Nurse in Antimicrobial Stewardship--Unrecognized, but Already There. AB - An essential participant in antimicrobial stewardship who has been unrecognized and underutilized is the "staff nurse." Although the role of staff nurses has not formally been recognized in guidelines for implementing and operating antimicrobial stewardship programs (ASPs) or defined in the medical literature, they have always performed numerous functions that are integral to successful antimicrobial stewardship. Nurses are antibiotic first responders, central communicators, coordinators of care, as well as 24-hour monitors of patient status, safety, and response to antibiotic therapy. An operational analysis of inpatient admissions evaluates these nursing stewardship activities and analyzes the potential benefits of nurses' formal education about, and inclusion into, ASPs. PMID- 26265497 TI - Effect of the 13-Valent Pneumococcal Conjugate Vaccine on Pneumococcal Meningitis in Children. PMID- 26265498 TI - The Impact of Age on the Efficacy of 13-valent Pneumococcal Conjugate Vaccine in Elderly. AB - In a post hoc analysis of the Community-Acquired Pneumonia (CAP) immunization Trial in Adults the model-predicted 13-valent pneumococcal conjugate vaccine efficacy for preventing vaccine-type specific CAP and Invasive Pneumococcal Disease declined from 65% to 40% for subjects being 65 and 75 year olds at the time of vaccination, respectively. PMID- 26265499 TI - Postpartum Engagement in HIV Care: An Important Predictor of Long-term Retention in Care and Viral Suppression. AB - BACKGROUND: Human immunodeficiency virus (HIV)-infected women are at risk of virologic failure postpartum. We evaluated factors influencing retention in care and viral suppression in postpartum HIV-infected women. METHODS: We conducted a retrospective cohort analysis (2005-2011) of 695 deliveries involving 561 HIV infected women in Philadelphia. Multivariable logistic regression evaluated factors, including maternal age, race/ethnicity, substance use, antiretroviral therapy during pregnancy, timing of HIV diagnosis, previous pregnancy with HIV, adequacy of prenatal care, and postpartum HIV care engagement (>= 1 CD4 count or viral load [VL] test within 90 days of delivery), associated with retention in care (>= 1 CD4 count or VL test in each 6-month interval of the period with >= 60 days between tests) and viral suppression (VL <= 200 copies/mL at the last measure in the period) at 1 and 2 years postpartum. RESULTS: Overall, 38% of women engaged in HIV care within 90 days postpartum; with 39% and 31% retained in care and virally suppressed, respectively, at 1 year postpartum, and 25% and 34% retained in care and virally suppressed, respectively, at 2 years postpartum. In multivariable analyses, women who engaged in HIV care within 90 days of delivery were more likely to be retained (adjusted odds ratio [AOR], 11.38; 95% confidence interval [CI], 7.74-16.68) and suppressed (AOR, 2.60 [95% CI, 1.82-3.73]) at 1 year postpartum. This association persisted in the second year postpartum for both retention (AOR, 6.19 [95% CI, 4.04-9.50]) and suppression (AOR, 1.40 [95% CI, 1.01-1.95]). CONCLUSIONS: The prevalence of postpartum HIV-infected women retained in care and maintaining viral suppression is low. Interventions seeking to engage women in care shortly after delivery have the potential to improve clinical outcomes. PMID- 26265501 TI - Medicine's social contract across borders. PMID- 26265500 TI - Evaluation of cytokine profile and HLA association in benznidazole related cutaneous reactions in patients with Chagas disease. AB - BACKGROUND: Benznidazole is the drug of choice for Chagas disease. The major drawback of this drug is the high adverse events rate, being cutaneous reactions the most frequent one, leading to definitive withdrawal of treatment in 15%-30% of patients. METHODS: Prospective observational study where adult Chagas disease patients accepting to receive benznidazole (100 mg/8 hours for 60 days) were included. The objective was to characterize the skin toxicity of benznidazole in patients with Chagas disease, determine the serum cytokine profile, and evaluate the potential association with specific HLA alleles and benznidazole concentration. Serum cytokine levels were measured at day 0, 15, and 60 of treatment. Class I and II HLA alleles were determined. When cutaneous reaction was detected, a skin biopsy was performed. Serum benznidazole concentration was determined at the time of cutaneous reaction, or at day 15 of treatment. RESULTS: Fifty-two patients were included, 20(38.5%) had cutaneous reaction, and median time of appearance was 9 days. Skin biopsies showed histopathological findings consistent with drug eruption. Patients with cutaneous drug-reaction had higher proportion of eosinophilia during treatment, and higher interleukin (IL)-5 and IL 10 serum concentrations at day 15 of treatment than those without cutaneous reaction. Treatment interruption (that included moderate-severe cutaneous reactions) was more frequent in patients carrying HLA-B*3505 allele (45.5% vs 15.4%, P = .033). No differences in benznidazole serum concentration were found. CONCLUSIONS: Benznidazole related cutaneous reaction rate is high, and it was produced by a delayed hypersensitivity reaction with a Th2 response. Carrying HLA B*3505 allele could be associated with moderate-severe cutaneous reaction. PMID- 26265502 TI - The relationship between smoking and unemployment: New avenues for interdisciplinary research. PMID- 26265503 TI - Colour, culture and placebo response. PMID- 26265504 TI - Sequences of talk about emotional concerns in follow-up consultations with adolescent childhood cancer survivors. AB - OBJECTIVE: To explore practices regarding communication about emotional concerns in follow-up consultations with adolescent cancer survivors and pediatrician. METHOD: Seven video-taped follow-up consultations with adolescent survivors which contained many examples of emotional cues and concern were analyzed according to principles of conversation analysis. RESULTS: During talk about emotional concerns, a task-focused asymmetric pattern of pediatrician questions and patient responses was most often upheld. In a number of cases a gradual build-up of emotional expression from a weak hint to a more explicit expression of emotional concern was observed, often facilitated by the pediatricians. Most often work-up was relatively brief, sometimes with a brief positive reappraisal, but more comprehensive elaboration was also seen. Topic shifts were often abrupt. CONCLUSION: Pediatricians and patients used some of the same conventions as in everyday conversation during emotional talk in medical encounters. We observed shifts between informal talk and a typical task-focused mode. Conscious attention to such shifts and to the sequential nature of emotional talk could be helpful for doctors in designing their responses to patients' emotional concerns. PRACTICE IMPLICATIONS: Our findings may contribute to insight in how clinicians respond to emotional concerns in follow-up consultations and have implications for communication skills training. PMID- 26265505 TI - Emergent Functionality and Controllability in Few-Layer Metasurfaces. AB - Recent progress in metamaterial research has successfully exceeded the limitations imposed by conventional materials and optical devices, enabling the manipulation of electromagnetic waves as desired. The distinct characteristics and controlling abilities of metamaterials make them ideal candidates for novel photonics devices not only in traditional optics but also for biological detection, medical science, and metrology. However, the controllability and functionality of both single-layer metasurfaces and bulk metamaterials are not sufficient to meet the requirements of emerging technologies; hence, new solutions must be found. As such technologies advance, new functionalities will emerge as different or identical single-layer metasurfaces are combined. Thus, innovation in few-layer metasurfaces will become an increasingly important line of research. Here, these metasurfaces are classified according to their functionalities and the few-layer metasurfaces that have been proposed up to now are presented in a clear sequence. It is expected that, with further development in this area, few-layer metasurfaces will play an important role in the family of optical materials. PMID- 26265507 TI - Neurotransmission: Sticking the brakes on. PMID- 26265506 TI - New insights into the biological role of the osmoregulated periplasmic glucans in pathogenic and symbiotic bacteria. AB - This review emphasizes the biological roles of the osmoregulated periplasmic glucans (OPGs). Osmoregulated periplasmic glucans occur in almost all alpha-, beta- and gamma-Proteobacteria. This polymer of glucose is required for full virulence. The roles of the OPGs are complex and vary depending on the species. Here, we outline the four major roles of the OPGs through four different pathogenic and one symbiotic bacterial models (Dickeya dadantii, Salmonella enterica, Pseudomonas aeruginosa, Brucella abortus and Sinorhizobium meliloti). When periplasmic, the OPGs are a part of the signal transduction pathway and indirectly regulate genes involved in virulence. The OPGs can also be secreted. When outside of the cell, they interact directly with antibiotics to protect the bacterial cell or interact with the host cell to facilitate the invasion process. When OPGs are not found, as in the epsilon-Proteobacteria, OPG-like oligosaccharides are present. Their presence strengthens the evidence that OPGs play an important role in virulence. PMID- 26265512 TI - Experience of knowledge and skills that are essential in self-managing a chronic condition - a focus group study among people with type 2 diabetes. AB - AIMS: The purpose of the study was to gain new knowledge about how people experience participating in diabetes self-management courses with other people with type 2 diabetes and how they perceive this influences their health and ability to self-manage the disease. METHODS: We conducted five focus groups with 22 people with type 2 diabetes who had participated in a group-based diabetes self-management course. We systematically coded the data and analysed them using Knodel's method. FINDINGS: Participants gained more nuanced and specific knowledge by participating in a group setting. They increased their theoretical and practical understanding of how to handle diabetes in everyday life. The diabetes self-management course made the participants more aware of having a disease they had to take more seriously. Learning by being in the situation while guided by professionals was useful. In addition, the participation learned from each other by carrying out real tasks in a context with others struggling with similar treatment demands. They wished more room to perform practical tasks and more independent activity. Further, they suggested to make parts of the course accessible online. Still, it was noted that web-based solutions cannot replace the practical parts or the dialogue between the participants. They expressed both a need and a wish for a refresher course. CONCLUSION: This study underscored that the participants learned through concrete experience, and by trying out practical tasks by becoming part of the diabetes community. They felt safer regarding their own treatment by experiencing a variety of situations in real-life scenarios. PMID- 26265513 TI - Functional limitations and somatic diseases are independent predictors for incident depressive disorders in seniors: Findings from a nationwide longitudinal study. AB - PURPOSE: Few nationwide comprehensive studies analyzed the factors leading to the onset of depression in correlation with medical disease and other related factors concerning geriatric depression. This study examined medical diseases with other factors which lead to depression among the elderly. METHODS: This Taiwan-based longitudinal study examined a collection of 1467 seniors aged over 65. Subjects who fit this criteria were initially interviewed in 2003, and then four years later. Independent variables included baseline demographics, chronic medical illnesses, and the change of subjects' self-perceived health status, functional limitations including ADL, IADL and mobility limitation factors. The dependent variable was the symptoms of incident depression, as ascertained by the ten-item questionnaire during the later session. The logistic regression analyses were used to examine some of the predictors related to depressive disorders. RESULTS: The findings showed that heart conditions (adjusted OR=1.55, 95% CI: 1.12-2.15, p=0.008) and joint disorders (adjusted OR=1.51, 95% CI: 1.09-2.09, p=0.013), as well as functional limitations, particularly IADL (adjusted OR=1.81, 95% CI: 1.24 2.65, p=0.002) and ADL (adjusted OR=1.77, 95% CI: 1.27-2.47, p=0.001) were independently associated with the onset of depression among the elderly population. CONCLUSION: These findings indicated that when classifying symptoms of depression in geriatric patients with several underlying medical diseases, keen attention should be directed to the type of medical disorders and the functional deterioration in terms of daily activities and autonomic capabilities. PMID- 26265514 TI - The Most Prevalent Causes of Deaths, DALYs, and Geriatric Syndromes in Iranian Elderly People Between 1990 and 2010: findings from the Global Burden of Disease study 2010. AB - BACKGROUND: The substantial increase in life expectancy during recent decades has left all countries with a high number of elderly people that have particular health needs. Health policy-makers must be aware of the most prevalent causes of deaths and DALYs in this age group, as well as geriatric syndromes, in order to provide appropriate care and allocate resources in an equitable manner. METHODS: The Global Burden of Disease study 2010 (GBD 2010), conducted by the institute for Health Metrics and Evaluation team, estimated the worldwide burden of diseases from 1990 to 2010. Its estimations were conducted on the basis of the proportion of deaths, the duration of symptoms and disability weights for sequelae, years lived with disability (YLDs), years of life lost (YLLs), and disability adjusted life years (DALYs) attributable to different diseases. In the present study, we extracted the data regarding the top five most prevalent causes of deaths, DALYs, and geriatric syndromes in the elderly based on the aforementioned GBD 2010, discussed the results using some tables and figures, reviewed the results, described the limitations of GBD 2010, and finally provided some recommendations as potential solutions. RESULTS: According to GBD 2010, the total number of deaths in Iran in 1990 was 321,627, of which 116,100 were in elderly people (those aged 60 years and above), meaning that 36.10% of all deaths occurred in the elderly. Among all diseases in this year, the first to third ranked causes of death were ischemic heart disease (IHD; 29.44%), neoplasms (13.52%), and stroke (7.24%). In comparison, the total number of deaths in Iran increased to 351,814 in 2010, with 213,116 of these occurring in the elderly (60.58% of deaths), but the most prevalent causes of death remained the same as in 1990. The highest 1990 DALYs rates were the result of IHD (21.56%), neoplasms (10.70%), and stroke (4.85%). IHD (22.77%), neoplasms (9.48%), and low back pain (LBP; 5.72%) were the most prevalent causes of DALYs in older Iranian adults in 2010. The fourth and fifth ranked causes of deaths and DALYs in both 1990 and 2010, both in Iran and globally, were different diseases and geriatric syndromes in the elderly Iranian population. CONCLUSION: The aged population of Iran is growing steadily, and there is a need for health policy-makers to create appropriate programs to meet the health needs of elderly people. Although GBD 2010 results are useful in providing burden estimations at regional and national levels, each individual country should estimate its burden of diseases, injuries, and risk factors at a sub-national level to obtain further details regarding the health status of its people. As no comprehensive study regarding elderly people in Iran has previously been conducted, our study will be a major source for identifying the important causes of deaths, DALYs, and geriatric syndromes among this population. PMID- 26265515 TI - Burden of Drug and Alcohol Use Disorders in Iran: findings from the Global Burden of Disease Study 2010. AB - BACKGROUND: Due to its specific socio-cultural and geographical situation, Iran has a major public health problem in terms of drug and alcohol use. The aim of this study is to report and critique the burden of drug and alcohol use disorders in Iran, and to compare these measurements with similar findings. METHODS: This study used data for Iran for the years 1990, 2005, and 2010 derived from the Global Burden of Disease study (GBD 2010) conducted by the Institute for Health Metrics and Evaluation (IHME) in 2010. The burden of drug and alcohol use disorders was evaluated in terms of disability adjusted life years (DALYs), years of life lost to premature mortality (YLLs), and years lived with disability (YLDs). RESULTS: All rates were reported per 100,000 individuals. Death rates attributed to drug and alcohol use disorders were 7.7 and 0.16 for men, and 0.62 and 0.02 for women, respectively. YLL rates regarding drug use disorders were 351.8 and 24.8 for men and women, while these figures were 5.8 and 1.0 for alcohol use disorders for men and women, respectively. YLD rates of drug use disorders were 452.6 for men and 202.1 for women, and 105.8 for men and 23.7 for women for alcohol use disorders. DALY rates attributed to drug use disorders were 804.5 for men and 227 for women, while these rates were 111.7 for men and 24.7 for women, related to alcohol use disorders. CONCLUSION: Similar to the cases in many other countries, the burden of both drug and alcohol use disorders is higher for men than women in Iran. Although prevention policies and programs for drug and alcohol use are required for both genders, the need for drug and alcohol use intervention seems more urgent for men in Iran. PMID- 26265516 TI - Burden of Oral Diseases in Iran, 1990-2010: Findings from the Global Burden of Disease Study 2010. AB - BACKGROUND: Oral diseases, as a group of chronic diseases, are among the major public health problems that lead to disability throughout the world. The major part of burden of oral diseases is caused by dental caries, periodontal diseases, edentulism, mouth cancer, cleft lip, and cleft palate. The aim of the present paper is to report the global results for the burden of oral disease in Iran from 1990 to 2010, derived from GBD study 2010 by sex and age. METHODS: The Global Burden of Disease Study 2010 (GBD 2010) was a systematic effort with a common framework to estimate disability adjusted life years (DALYs) for diseases in different parts of the world. Years of life lost due to premature mortality (YLLs) were assessed based on cause-of-death estimates and by means of a cause of death ensemble model (CODEm). Years of life lost due to disability (YLDs) were computed by multiplying the prevalence, the disability weight for a sequel, and the duration of symptoms. A systematic review of published and unpublished data was conducted to estimate disease distribution using a Bayesian meta-regression method (DisMod-MR). Disability weights were measured by collecting data from population-based surveys. In this paper, we describe the results of GBD 2010 regarding oral diseases in Iran, critique the results, and provide some recommendations. RESULTS: Between 1990 and 2010 in Iran, an increase occurred in DALYs at all ages, attributed to dental caries (from 37,230 to 56,521) as well as periodontal diseases (from 21,482 to 43,308), and a decrease was found for edentulism (from 53,134 to 47,960). DALYs at all ages attributed to mouth cancer increased (from 5,597 to 7,771), while a decline was noted for cleft lip and cleft palate (from 6,157 to 5,034). The age-standardized DALY rates per 100,000 population did not considerably change for dental caries and periodontal diseases, while edentulism showed a reduction. The corresponding DALY rate due to mouth cancer decreased, while it remained almost unchanged for cleft lip and cleft palate over this period. DALY rates per 100,000 population due to dental caries and edentulism were higher among Iranian women than for Iranian men at all ages, while Iranian men suffered from a higher burden of periodontal disease, mouth cancer, cleft lip, and cleft palate. The most significant burden due to dental caries and periodontal diseases was found in Iranians aged 15-49 and 50-69 years, respectively and edentulism and mouth cancer led to the highest burden in Iranians older than 70 years of age. The highest burden caused by cleft lip and cleft palate occurred in children younger than 5 years old. CONCLUSION: The findings address the challenging changes in oral diseases and difficulties in responding to the urgent oral health needs in Iran. The burden of oral diseases should be considered as a priority in Iran. A need also exists to pay more attention to the oral health policies and principles of preventive oral care. Global analyses of disease burdens provide a useful framework to guide a suitable policy in response to disease changes. In fact, strong national and sub-national analyses will be required to provide more effective public health strategies. PMID- 26265517 TI - Tobacco Smoking Status and the Contribution to Burden of Diseases in Iran, 1990 2010: findings from the Global Burden of Disease Study 2010. AB - BACKGROUND: Tobacco smoking and exposure to second-hand smoke in the indoor environment are major public health risks worldwide. The aim of this paper is to report and critique a global assessment of smoking prevalence, smoking attributable deaths, and disability adjusted life years (DALYs) extracted from GBD study 2010, by sex and age in Iran from 1990 to 2010. METHODS: The Global Burden of Disease (GBD) Study 2010 estimated the distributions of exposure and relative risks per unit of exposure by systematically reviewing and analyzing published and unpublished data. These assessments were used, together with estimates of death and DALYs due to specific risk factors, to calculate the attributed burden for each risk factor exposure compared with the theoretical minimum-risk exposure. Uncertainties in the distribution of exposure, relative risks, and relevant outcomes were incorporated into estimates of attributable mortality and burden. In this study, our aim was to reformulate the GBD data, produce new graphs, and explain the results for Iran in greater detail. RESULTS: Between 1990 and 2010, the prevalence of tobacco smoking at all ages increased by 1% in men and declined by 2% in women in Iran, but the overall prevalence in the general population was unchanged (12%). A reduction was observed in the age standardized death and DALY rates (per 100,000 population) attributed to tobacco smoking, including second-hand smoke. The attributed DALY rate was greater for Iranian men than for Iranian women. The highest rates of DALYs because of tobacco smoking were found in smoker men and women aged 70+, but exposure to second-hand smoke had the most significant burden in children under 5 years old. In 1990, the three leading disease burdens attributed to tobacco smoking, including second hand smoke, were ischemic heart disease; communicable, maternal, neonatal, and nutritional disorders; and chronic respiratory diseases. In 2010, three leading burden of diseases attributed to tobacco smoking belonged to ischemic heart disease, chronic respiratory disease, and, and cerebrovascular disease, respectively. CONCLUSION: Despite a reduction in the rate of tobacco smoking, including second-hand smoke, since 1990, smoking exposure remained the fifth leading risk factor for deaths and DALYs in Iran in 2010. Overall, our data clearly show the need for new efforts in Iran to reduce the mortality and burden attributed to tobacco smoking. PMID- 26265518 TI - Burden of Hemoglobinopathies (Thalassemia, Sickle Cell Disorders and G6PD Deficiency) in Iran, 1990-2010: findings from the Global Burden of Disease Study 2010. AB - BACKGROUND: Hemoglobinopathies are known as the most common genetic disorders in Iran. The paper aims to provide global estimates of deaths and disability adjusted life years (DALYs) due to hemoglobinopathies in Iran by sex and age during 1990 to 2010 and describe the challenges due to limitations of the Global Burden of Disease Study 2010 (GBD 2010). METHODS: GBD 2010 estimates of the numbers of deaths and years of life lost (YLLs) due to premature mortality were calculated using the Cause of Death Ensemble model (CODEm). Years of life lost due to disability (YLDs) were computed by multiplication of prevalence, the disability weight for occurrence of sequelae, and the duration of symptoms. Prevalence was estimated through a systematic search of published and available unpublished data sources, with a Bayesian meta-regression model developed for GBD 2010. Disability weights were produced using collected data from population-based surveys. Uncertainty from all inputs was incorporated into the computations of DALYs using simulation methods. We aim to prepare and criticize the results of GBD 2010 and provide some recommendations for reaching better conclusions about the burden of hemoglobinopathies in Iran. RESULTS: Between 1990 and 2010, the overall deaths attributed to hemoglobinopathies decreased from 0.51% to 0.36% of total deaths, with the corresponding burden declining from 1% to 0.82% of total DALYs. There was a reduction in deaths and DALYs rates for all ages and the rates attributed to all ages followed the same pattern in Iranian men and women. The highest DALYs for hemoglobinopathies, thalassemia, sickle cell disorder, and glucose-6-phosphate dehydrogenase deficiency (G6PD-D) were found in those aged less than 5 years. The collective burden of all of these hemoglobin disorder was lower in 2010 than in 1990. CONCLUSION: Although the screening programs in Iran have been very successful in reducing the number of thalassemia patients between 1990 to 2010, in order to provide a better estimation of the burden of hemoglobin disorders, it is necessary to perform a national and sub-national study of hemoglobinopathies using multiple national and sub-national surveys. PMID- 26265519 TI - Burden of Hepatitis C in Iran Between 1990 and 2010: findings from the Global Burden of Disease Study 2010. AB - BACKGROUND: Hepatitis C virus (HCV) is the foremost cause of deaths attributable to cirrhosis and hepatocellular carcinoma. The Global Burden of Disease study 2010 (GBD 2010) quantifies and compares the degree of health loss as a result of diseases, injuries, and risk factors by age, sex, and geography overtime. This study aimed to present and critique the burden of hepatitis C and its trend in Iran between 1990 and 2010 by using the GBD study 2010. METHODS: We used the results of GBD 2010 for Iran to measure rates and trends of mortality, causes of deaths, years of life lost (YLLs), years lived with disability (YLDs), and disability adjusted life years (DALYs) due to hepatitis C. Hepatitis C was defined as the presence of hepatitis C virus in the serum. Data were presented in three categories: acute hepatitis C, cirrhosis secondary to hepatitis C, and liver cancer secondary to hepatitis C. RESULTS: HCV infection (including the three categories of the study) led to 57.29, 59.92, and 66.45 DALYs (per 100,000 population) in 1990, 2000, and 2010, respectively. DALYs and death rates showed a slight decreasing trend for HCV cirrhosis; however, DALYs and death rates increased for acute hepatitis and liver cancer due to patients with HCV. The majority of deaths and DALYs were in individuals aged 70 years and above in all three categories of HCV. YLLs made the greatest contributions to DALYs. CONCLUSION: DALYs due to HCV infection are increasing in Iran according to GBD 2010; however, the estimations of DALYs using GBD 2010 are mostly from model based data and there are significant uncertainties for extrapolated data. In this regard, a comprehensive study such as the National and Subnational Burden of Diseases (NASBOD) study would be needed to estimate and calculate precisely prevalence and burden of HCV-related diseases at national and subnational levels. PMID- 26265520 TI - PolyPill for Prevention of Cardiovascular Disease in an Urban Iranian Population with Special Focus on Nonalcoholic Steatohepatitis: A Pragmatic Randomized Controlled Trial within a Cohort (PolyIran - Liver) - Study Protocol. AB - BACKGROUND: Cardiovascular disease (CVD) is among the most common causes of mortality in all populations. Nonalcoholic steatohepatitis is a common finding in patients with CVD. Prevention of CVD in individual patients typically requires periodic clinical evaluation, as well as diagnosis and management of risk factors such as hypertension and hyperlipidemia. However, this is resource consuming and hard to implement, especially in developing countries. We designed a study to investigate the effects of a simpler strategy: a fixed-dose combination pill consisting of aspirin, valsartan, atorvastatin and hydrochlorthiazide (PolyPill) in an unselected group of persons aged over 50 years. DESIGN: The PolyIran-Liver study was performed in Gonbad city as an open label pragmatic randomized controlled trial nested within the Golestan Cohort Study. We randomly selected 2,400 cohort study participants aged above 50 years, randomly assigned them to intervention or usual care and invited them to participate in an additional measurement study (if they met the eligibility criteria) to measure liver related outcomes. Those agreeing and randomized to the intervention arm were offered a daily single dose of PolyPill. We will follow participants for 5 years. The primary outcome is major cardiovascular events, secondary outcomes include all cause mortality and liver related outcomes: liver stiffness and liver enzyme levels. Cardiovascular outcomes and mortality will be determined from the cohort study and liver-related outcomes in those consenting to follow up. Analysis will be by allocated group. TRIAL STATUS: Between October and December 2011, 1,320 intervention and 1,080 control participants were invited to participate in the additional measurement study. For all these participants, the major cardiovascular events will be determined using blind assessment of outcomes through the cohort study. In the intervention and control arms, 875 (66%) and 721 (67%) respectively, met the eligibility criteria and agreed to participate in the additional measurement study. Liver related outcomes will be measured in these participants. Of the 1,320 participants randomized to the intervention, 787 (60%) accepted the PolyPill. CONCLUSION: The PolyIran-liver urban study will provide us with important information on the effectiveness of PolyPill on major cardiovascular events, all-cause mortality and liver related outcomes. (ClinicalTrials.gov ID: NCT01245608). PMID- 26265521 TI - MicroRNA-21: Mechanisms of Oncogenesis and its Application in Diagnosis and Prognosis of Gastric Cancer. AB - Gastric cancer is a silent killer, claiming more than seven hundred thousand lives every year. This heavy burden creates an irrefutable need for accurate, noninvasive methods of population screening and early detection as well as disease monitoring and management. Gastric cancer is a multi-factorial disease with an uneven geographic distribution, mostly affecting the developing countries and Southeast Asia. The multi-dimensional roles of microRNAs in gene regulation and tumorigenesis have prompted investigators to explore their potentials in diagnosis and treatment of various cancers, including gastric cancer. In this respect, miR-21 has attracted much attention as well as generating some controversies. Here, we aim to describe, in a chronological order, the numerous studies which have explored 1) the interactions of this oncomir with Helicobacter pylori infection, as a class I gastric carcinogen, 2) its potential mechanisms of oncogenicity, by various induction/inhibition assays, and 3) its application as a diagnostic/prognostic invasive (tissue) and non-invasive (circulating) biomarker. PMID- 26265523 TI - Bilateral Femoral Neck Fatigue Fracture due to Osteomalacia Secondary to Celiac Disease: Report of Three Cases. AB - Bilateral non traumatic femoral neck fatigue fracture is a rare condition usually occurring secondary to medical conditions such as pregnancy, pelvic irradiation, corticosteroid exposure, chronic renal failure and osteomalacia. In this report, we present three young female patients with bilateral femoral neck fracture secondary to osteomalacia. The underlying cause of osteomalacia was Celiac disease in all patients. The patients were treated with closed reduction and internal fixation with cannulated lag screws. They were free of pain and full weight bearing was achieved at three months. There were no complications, avascular necrosis and nonunion during the follow up period. In patients with bone pain, non traumatic fractures and muscle weakness, osteomalacia should be kept in mind and proper diagnostic work-up should be performed to identify the underlying cause of osteomalacia such as celiac disease. PMID- 26265522 TI - Myeloid Antigen-positive T Cell Acute Lymphocytic Leukemia with t(14;18) and Trisomy 10: Report of a Case and Literature Review. AB - The chromosomal translocation t(14;18)(q32;q21) is commonly associated with neoplasms of follicular center cell origin and has also been reported in cases of chronic lymphocytic leukemia. However, T cell acute lymphoblastic (or lymphocytic) leukemia (T-ALL) with t(14;18)(q32;q21) has been rarely reported. Here, we report a case of myeloid antigen-positive T-ALL (My+T-ALL) with t(14;18)(q32;q21) and trisomy 10. This is the first reported case of My+T-ALL (L2) with such chromosomal abnormalities. Other published de novo ALL cases, with t(14;18)(q32;q21) and without a documented history of lymphoma, are summarized and reviewed in this report. The patient in this study was treated with remission induction therapy and intensive chemotherapy, followed by maintenance therapy. As of this writing, he has remained in remission for more than 3 years and has presented a better clinical outcome compared with other reported adult ALL patients with t(14;18)(q32;q21). PMID- 26265524 TI - Refractory Hyperlactatemia with Organ Insufficiency in Lipid Storage Myopathy. AB - Lipid storage myopathy is a metabolic disorder characterized by abnormal lipid accumulation in muscle fibers and progressive muscle weakness. Here, we report the case of a 17-year-old woman with progressive muscle weakness, refractory hyperlactatemia, and multiple organ insufficiency. Severe pneumonia was the initial diagnosis. After anti-infective treatment, fluid resuscitation, and mechanical ventilation, the patient's symptoms improved but hyperlactatemia and muscle weakness persisted. She was empirically treated with carnitine. Biochemical tests, electromyography, and muscle biopsy confirmed lipid storage myopathy. After 7 weeks of treatment, the patient resumed normal daily life. An empirical treatment with carnitine may be beneficial for patients before an accurate diagnosis of lipid storage myopathy is made. PMID- 26265525 TI - A Brief History of Ancient Iranian Medicine. PMID- 26265526 TI - Professor Parviz Haghighi and His Role in Promotion of Academic Pathology at the Shiraz School of Medicine in Iran (1969-1979). PMID- 26265527 TI - Establishment of the National Network of WHO Collaborating Centres in Iran to Contribute to the National Public Health Needs. PMID- 26265528 TI - Mansour Haghshenas, MD. PMID- 26265530 TI - Determination of Milk Fat Adulteration with Vegetable Oils and Animal Fats by Gas Chromatographic Analysis. AB - This study assessed the potential application of gas chromatography (GC) in detecting milk fat (MF) adulteration with vegetable oils and animal fats and of characterizing samples by fat source. One hundred percent pure MF was adulterated with different vegetable oils and animal fats at various concentrations (0%, 10%, 30%, 50%, 70%, and 90%). GC was used to obtain the fatty acid (FA) profiles, triacylglycerol (TG) contents, and cholesterol contents. The pure MF and the adulterated MF samples were discriminated based on the total concentrations of saturated FAs and on the 2 major FAs (oleic acid [C18:1n9c] and linoleic acid [C18:2n6c], TGs [C52 and C54], and cholesterol contents using statistical analysis to compared difference. These bio-markers enabled the detection of as low as 10% adulteration of non-MF into 100% pure MF. The study demonstrated the high potential of GC to rapidly detect MF adulteration with vegetable and animal fats, and discriminate among commercial butter and milk products according to the fat source. These data can be potentially useful in detecting foreign fats in these butter products. Furthermore, it is important to consider that several individual samples should be analyzed before coming to a conclusion about MF authenticity. PMID- 26265529 TI - Hybrid flagellin as a T cell independent vaccine scaffold. AB - BACKGROUND: To extend the potency of vaccines against infectious diseases, vaccines should be able to exploit multiple arms of the immune system. One component of the immune system that is under-used in vaccine design is the subset of B cells known to be capable of responding to repetitive antigenic epitopes and differentiate into plasma cells even in the absence of T cell help (T independent, TI). RESULTS: To target vaccine responses from T-independent B cells, we reengineered a bacterial Flagellin (FliC) by replacing its exposed D3 domain with a viral envelope protein from Dengue virus (DENV2). The resulting hybrid FliC protein (hFliC) was able to form stable filaments decorated with conformationally intact DENV2 envelope domains. These filaments were not only capable of inducing a T cell-dependent (TD) humoral antibody response, but also significant IgM and IgG3 antibody response in a helper T cell repertoire restricted transgenic mouse model. CONCLUSIONS: Our results provide proof-of principle demonstration that a reengineered hybrid FliC could be used as a platform for polymeric subunit vaccines, enhancing T cell-dependent and possibly inducing T-independent antibody responses from B-1 B cells as well. PMID- 26265531 TI - Identification of 1H-indene-(1,3,5,6)-tetrol derivatives as potent pancreatic lipase inhibitors using molecular docking and molecular dynamics approach. AB - Pancreatic lipase is a potential therapeutic target to treat diet-induced obesity in humans, as obesity-related diseases continue to be a global problem. Despite intensive research on finding potential inhibitors, very few compounds have been introduced to clinical studies. In this work, new chemical scaffold 1H-indene (1,3,5,6)-tetrol was proposed using knowledge-based approach, and 36 inhibitors were derived by modifying its functional groups at different positions in scaffold. To explore binding affinity and interactions of ligands with protein, CDOCKER and AutoDock programs were used for molecular docking studies. Analyzing results of rigid and flexible docking algorithms, inhibitors C_12, C_24, and C_36 were selected based on different properties and high predicted binding affinities for further analysis. These three inhibitors have different moieties placed at different functional groups in scaffold, and to characterize structural rationales for inhibitory activities of compounds, molecular dynamics simulations were performed (500 nSec). It has been shown through simulations that two structural fragments (indene and indole) in inhibitor can be treated as isosteric structures and their position at binding cleft can be replaced by each other. Taking into account these information, two lines of inhibitors can further be developed, each line based on a different core scaffold, that is, indene/indole. PMID- 26265533 TI - Erratum. PMID- 26265532 TI - Patient-Centered mHealth Living Donor Transplant Education Program for African Americans: Development and Analysis. AB - BACKGROUND: There is a critical need to expand the pool of available kidneys for African Americans who are on the transplant wait-list due to the disproportionally lower availability of deceased donor kidneys compared with other races/ethnic groups. Encouraging living donation is one method to fill this need. Incorporating mHealth strategies may be a way to deliver educational and supportive services to African American transplant-eligible patients and improve reach to those living in remote areas or unable to attend traditional group session-based programs. Before program development, it is essential to perform formative research with target populations to determine acceptability and cultivate a patient-centered and culturally relevant approach to be used for program development. OBJECTIVE: The objectives of this study were to investigate African American kidney transplant recipients' and kidney donors'/potential donors' attitudes and perceptions toward mobile technology and its viability in an mHealth program aimed at educating patients about the process of living kidney donation. METHODS: Using frameworks from the technology acceptance model and self determination theory, 9 focus groups (n=57) were administered to African Americans at a southeastern medical center, which included deceased/living donor kidney recipients and living donors/potential donors. After a demonstration of a tablet-based video education session and explanation of a group-based videoconferencing session, focus groups examined members' perceptions about how educational messages should be presented on topics pertaining to the process of living kidney donation and the transplantation. Questionnaires were administered on technology use and perceptions of the potential program communication platform. Transcripts were coded and themes were examined using NVivo 10 software. RESULTS: Qualitative findings found 5 major themes common among all participants. These included the following: (1) strong support for mobile technology use; (2) different media formats were preferred; (3) willingness to engage in video chats, but face-to-face interaction sometimes preferred; (4) media needs to be user friendly; (5) high prevalence of technology access. Our results show that recipients were willing to spend more time on education than the donors group, they wanted to build conversation skills to approach others, and preferred getting information from many sources, whereas the donor group wanted to hear from other living donors. The questionnaires revealed 85% or more of the sample scored 4+ on a 5-point Likert scale, which indicates high degree of interest to use the proposed program, belief that other mHealth technologies would help with adherence to medical regimens, and doctors would make regimen adjustments quicker. In addition, high utilization of mobile technology was reported; 71.9% of the participants had a mobile phone and 43.9% had a tablet. CONCLUSIONS: Our study supports the use of an mHealth education platform for African Americans to learn about living donation. However, potential recipients and potential donors have differing needs, and therefore, programs should be tailored to each target audience. PMID- 26265538 TI - Effect of lentiviral vector overexpression alpha-calcitonin gene-related peptide on titanium implant osseointegration in alpha-CGRP-deficient mice. AB - alpha-Calcitonin gene-related peptide (alpha-CGRP) plays a significant pathophysiological role in bone development, metabolism and remodeling around dental implants. However, the half-life of alpha-CGRP in plasma is only 10min, which affects its long-time application and an alternative approach should be developed to deliver alpha-CGRP over long periods of time. The aim of this study is to investigate whether a lentiviral alpha-CGRP overexpression vector system can express this target-gene longer at peri-implant sites, thus enhancing osseointegration. Animals were divided to the following groups: alpha-CGRP-/-, alpha-CGRP-/- with lentivirus transfection and alpha-CGRP+/+ mice. IVIS Spectrum imaging observations identified the successful transfection of alpha-CGRP around experimental implants inserted in the femurs at 5days after injection. Histomorphometrical analysis indicated an increase of bone-implant contact (BIC) at 1-month healing in the transfection group. Moreover, real-time RT-PCR and western blot results of bone-related markers Runx2, Osterix, and BSP levels elevated in lentivirus-transfected mice at 21days, compared to the untreated alpha-CGRP-/- mice. There was no significant difference between the transfection group and alpha-CGRP+/+ group. Further alpha-CGRP protein detection confirmed the persistent expression of this transgene at 21days post-operatively. These results suggest that this lentiviral vector system expresses alpha-CGRP in an effective, appropriate and sustained manner, which might have a potential application in enhancing titanium implant osseointegration. PMID- 26265539 TI - Proliferation-coupled osteoclast differentiation by RANKL: Cell density as a determinant of osteoclast formation. AB - Although it is widely recognized that the osteoclast differentiation induced by RANKL is linked to the anti-proliferative activity of the cytokine, we report here that RANKL in the presence of M-CSF actually stimulates DNA synthesis and cell proliferation during the early proliferative phase (0-48 h) of osteoclastogenesis ex vivo, while the same cytokine exerts an anti-proliferative activity in the latter half (48-96 h). A tracing of the individual cells using Fucci cell cycle indicators showed that waves of active DNA synthesis in the S phase during the period 0-48 h are followed by cell-cycle arrest and cell fusion after 48 h. Inhibition of DNA synthesis with hydroxyurea (HU) during the first half almost completely inhibited osteoclastogenesis; however, the same HU-treated cells, when re-plated at 48 h at increasing cell densities, exhibited restored osteoclast formation, suggesting that a sufficient number of cells, rather than prior DNA synthesis, is the most critical requirement for osteoclast formation. In addition, varying either the number of bone marrow macrophages at the start of osteoclastogenic cultures or pre-osteoclasts halfway through the process had a substantial impact on the number of osteoclasts that finally formed, as well as the timing of the peak of osteoclast formation. Thus, caution should be exerted in the performance of any manipulative procedure, whether pharmacological or genetic, that affects the cell number prior to cell fusion. Such procedures can have a profound effect on the number of osteoclasts that form, the final outcome of "differentiation", leading to misinterpretation of the results. PMID- 26265540 TI - Teaching and learning in the Biosciences: the development of an educational programme to assist student nurses in their assessment and management of patients with wounds. AB - AIMS AND OBJECTIVES: The aim of this project was to develop an educational package for undergraduate student nurses that would provide them with the theoretical knowledge and clinical judgement skills to care for a patient with a wound. BACKGROUND: Internationally there is concern over the adequacy of preparation of undergraduate nurses for the clinical skill of wound care. Deficits have also been identified in the underpinning biological sciences needed for this skill. Expectations associated with wound management have altered significantly in the last two decades with decision making around wound care coming under the scope of practice of nurses. The treatment and care options for patients with wounds must be based on a sound knowledge of how wounds are formed and healed. If nurses do not have the evidence-based knowledge, it can affect wound healing adversely leading to increased patient suffering, pain and delayed healing. From an organisational perspective, delayed healing will increase the cost of care. DESIGN: This project used constructivism learning theory to provide a framework for the development of a wound care educational package for undergraduate Irish nurses in their penultimate year of training. METHODS: Collaboration was formed with key stake holders. Pertinent curriculum content was mapped. Learning strategies to suit the incoming student learning styles were incorporated into newly developed theoretical content and practical skill sessions. CONCLUSION: The developed educational programme will assist student nurses in their care of patients with wounds. RELEVANCE TO CLINICAL PRACTICE: This study provides a model that can be followed to develop small units of the study to keep abreast of changes in health care delivery and the changing scope of practice of nurses. It also contributes to the debate on the teaching and learning of biosciences as it highlights the depth of biological knowledge required as a basis for good evidence-based nursing care. PMID- 26265541 TI - Discussing the putative role of obesity-associated genes in the etiopathogenesis of eating disorders. AB - In addition to the identification of mutations clearly related to Mendelian forms of obesity; genome-wide association studies and follow-up studies have in the last years pinpointed several loci associated with BMI. These genetic alterations are located in or near genes expressed in the hypothalamus that are involved in the regulation of eating behavior. Accordingly, it seems plausible that these SNPs, or others located in related genes, could also help develop aberrant conduct patterns that favor the establishment of eating disorders should other susceptibility factors or personality dimensions be present. However, and somewhat surprisingly, with few exceptions such as BDNF, the great majority of the genes governing these pathways remain untested in patients with anorexia nervosa, bulimia nervosa or binge-eating disorder. In the present work, we review the few existing studies, but also indications and biological concepts that point to these genes in the CNS as good candidates for association studies with eating disorder patients. PMID- 26265542 TI - Seek, and Ye Shall Find: Comment on "Primary and Secondary Stabbing Headache". PMID- 26265543 TI - Cancer Prevalence among a Cross-sectional Survey of Female Orthopedic, Urology, and Plastic Surgeons in the United States. AB - BACKGROUND: Exposure to ionizing radiation from fluoroscopy performed during surgery, although low and within established limits, remains a health concern among surgeons. Estimates of breast cancer prevalence among women across surgery specialties with different patterns of fluoroscopy use are needed to evaluate this concern. METHODS: Female U.S. surgeons in urology, plastics, and orthopedics were identified using national directories and mailed surveys to collect information on occupational and medical history, including cancer diagnoses. Standardized prevalence ratios (SPRs) and 95% CIs were calculated by dividing the observed number of cancers among female surgeons in each specialty by the expected number, based on the gender-specific, age-specific, and race-specific cancer prevalence statistics in the general U.S. RESULTS: Standard fluoroscopy use more than once per week was common among urologists (54%) and orthopedists (37%); the same frequency of mini fluoroscopy use was only common among orthopedics (31%) and hardly ever used by urologists. Plastic surgeons reported very infrequent use of any fluoroscopy. For orthopedic surgeons, a significantly greater than expected prevalence of any cancer (SPR, 1.85; 95% CI, 1.19-2.76) and breast cancer (SPR, 2.90; 95% CI, 1.66-4.71) were observed. There was no difference between the observed and expected prevalence of any cancer or breast cancer for urology or plastics. CONCLUSIONS: Using the first available cancer prevalence data comparing female surgeons across three specialties, we report that orthopedic surgeons have a greater than expected prevalence of cancer that may or may not be owing to occupational exposure to ionizing radiation. PMID- 26265544 TI - A functional tandem between transient receptor potential canonical channels 6 and calcium-dependent chloride channels in human epithelial cells. AB - TRPC6 plays important human physiological functions, notably in artery and arterioles constriction, in regulation of vascular volume and in bronchial muscle constriction. It is implicated in pulmonary hypertension, cardiovascular disease, and focal segmental glomerulosclerosis and seems to play a role in cancer development. Previously, we identified Guanabenz, an alpha2-adrenergic agonist used for hypertension treatment (Wytensin(r)), as an activator of calcium dependent chloride channels (CaCC) in human Cystic Fibrosis (CF) nasal epithelial cells by transiently increasing [Ca2+]i via an influx of extracellular Ca2+. In this study, using assays to measure chloride channel activity, we show that guanabenz is an activator of CaCC in freshly dissociated human bronchial epithelial cells from three CF patients with various genotypes (F508del/F508del, F508del/R1066C, F508del/H1085R). We further characterised the effect of guanabenz and show that it is independent of alpha-adrenergic receptors, is inhibited by the TRPC family inhibitor SKF-96365 but not by the TRPV family inhibitor ruthenium red. Using western-blotting, Ca2+ measurements and iodide efflux assay, we found that TRPC1 siRNA has no effect on guanabenz induced responses whereas TRPC6 siRNA prevented the guanabenz-dependent Ca2+ influx and the CaCC-dependent activity stimulated by guanabenz. In conclusion, we show that TRPC6 channel is pivotal for the activation of CaCC by guanabenz through a alpha2-adrenergic independent pathway in human airway epithelial cells. We suggest propose a functional coupling between TRPC6 and CaCC and guanabenz as a potential TRPC6 activator for exploring TRPC6 and CaCC channel functions and corresponding channelopathies. PMID- 26265546 TI - Studying host-microbiota interactions in Drosophila melanogaster. PMID- 26265547 TI - Awareness and practice patterns of family planning methods among antenatal women in Indian community: Are we hitting the bull's eye? AB - A questionnaire-based cross-sectional survey was undertaken to assess the awareness and practice patterns of family planning among the antenatal women in North India. The study included 400 respondents. Three-fourths of the respondents (74.2%, n = 297) were aware of family planning methods. Condoms were the most commonly used family planning method (78.2%), while intrauterine devices and oral contraceptive pills were used by 25.5% and 16.7% respondents, respectively. The main reasons cited for not using contraception were inadequate knowledge and fear of side-effects. Post counseling, 90.5% (n = 362) of the respondents clearly conveyed their desire to use one of the family planning methods in the postpartum period. Awareness and acceptance of family planning methods in the Indian community needs strengthening. Family planning counseling during antenatal check up is likely to increase the acceptance of family planning methods in the postpartum period. PMID- 26265548 TI - Meta-analysis comparing early versus delayed laparoscopic cholecystectomy for acute cholecystitis. AB - BACKGROUND: Previous studies comparing early laparoscopic cholecystectomy (ELC) with delayed laparoscopic cholecystectomy (DLC) for acute cholecystitis were incomplete. A meta-analysis was undertaken to compare the cost-effectiveness, quality of life, safety and effectiveness of ELC versus DLC. METHODS: PubMed, Embase, the Cochrane Library and Web of Science were searched for randomized clinical trials (RCTs) that compared ELC (performed within 7 days of symptom onset) with DLC (undertaken at least 1 week after symptoms had subsided) for acute cholecystitis. RESULTS: Sixteen studies reporting on 15 RCTs comprising 1625 patients were included. Compared with DLC, ELC was associated with lower hospital costs, fewer work days lost (mean difference (MD) -11.07 (95 per cent c.i. -16.21 to -5.94) days; P < 0.001), higher patient satisfaction and quality of life, lower risk of wound infection (relative risk 0.65, 95 per cent c.i. 0.47 to 0.91; P = 0.01) and shorter hospital stay (MD -3.38 (-4.23 to -2.52) days; P < 0.001), but a longer duration of operation (MD 11.12 (4.57 to 17.67) min; P < 0.001). There were no significant differences between the two groups in mortality, bile duct injury, bile leakage, conversion to open cholecystectomy or overall complications. CONCLUSION: For patients with acute cholecystitis, ELC appears as safe and effective as DLC. ELC might be associated with lower hospital costs, fewer work days lost, and greater patient satisfaction. PMID- 26265549 TI - Tone-language speakers show hemispheric specialization and differential cortical processing of contour and interval cues for pitch. AB - Electrophysiological studies demonstrate that the neural coding of pitch is modulated by language experience and the linguistic relevance of the auditory input; both rightward and leftward asymmetries have been observed in the hemispheric specialization for pitch. In music, pitch is encoded using two primary features: contour (patterns of rises and falls) and interval (frequency separation between tones) cues. Recent evoked potential studies demonstrate that these "global" (contour) and "local" (interval) aspects of pitch are processed automatically (but bilaterally) in trained musicians. Here, we examined whether alternate forms of pitch expertise, namely, tone-language experience (i.e., Chinese), influence the early detection of contour and intervallic deviations within ongoing pitch sequences. Neuroelectric mismatch negativity (MMN) potentials were recorded in Chinese speakers and English-speaking nonmusicians in response to continuous pitch sequences with occasional global or local deviations in the ongoing melodic stream. This paradigm allowed us to explore potential cross-language differences in the hemispheric weighting for contour and interval processing of pitch. Chinese speakers showed differential pitch encoding between hemispheres not observed in English listeners; Chinese MMNs revealed a rightward bias for contour processing but a leftward hemispheric laterality for interval processing. In contrast, no asymmetries were observed in the English group. Collectively, our findings suggest tone-language experience sensitizes auditory brain mechanisms for the detection of subtle global/local pitch changes in the ongoing auditory stream and exaggerates functional asymmetries in pitch processing between cerebral hemispheres. PMID- 26265551 TI - Animal models of recurrent or bipolar depression. AB - Animal models of mental disorders should ideally have construct, face, and predictive validity, but current animal models do not always satisfy these validity criteria. Additionally, animal models of depression rely mainly on stress-induced behavioral changes. These stress-induced models have limited validity, because stress is not a risk factor specific to depression, and the models do not recapitulate the recurrent and spontaneous nature of depressive episodes. Although animal models exhibiting recurrent depressive episodes or bipolar depression have not yet been established, several researchers are trying to generate such animals by modeling clinical risk factors as well as by manipulating a specific neural circuit using emerging techniques. PMID- 26265550 TI - Cold stress protein RBM3 responds to temperature change in an ultra-sensitive manner in young neurons. AB - Extremely mild hypothermia to 36.0 degrees C is not thought to appreciably differ clinically from 37.0 degrees C. However, it is possible that 36.0 degrees C stimulates highly sensitive hypothermic signaling mechanism(s) and alters biochemistry. To the best of our knowledge, no such ultra-sensitive pathway/mechanisms have been described. Here we show that cold stress protein RNA binding motif 3 (RBM3) increases in neuron and astrocyte cultures maintained at 33 degrees C or 36 degrees C for 24 or 48 h, compared to 37 degrees C controls. Neurons cultured at 36 degrees C also had increased global protein synthesis (GPS). Finally, we found that melatonin or fibroblast growth factor 21 (FGF21) augmented RBM3 upregulation in young neurons cooled to 36 degrees C. Our results show that a 1 degrees C reduction in temperature can induce pleiotropic biochemical changes by upregulating GPS in neurons which may be mediated by RBM3 and that this process can be pharmacologically mimicked and enhanced with melatonin or FGF21. PMID- 26265552 TI - A novel method for early diagnosis of Alzheimer's disease based on pseudo Zernike moment from structural MRI. AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common type of dementia among older people. The number of patients with AD will grow rapidly each year and AD is the fifth leading cause of death for those aged 65 and older. In recent years, one of the main challenges for medical investigators has been the early diagnosis of patients with AD because an early diagnosis can provide greater opportunities for patients to be eligible for more clinical trials and they will have enough time to plan for future, medical and financial decisions. An established risk factor for AD is mild cognitive impairment (MCI) which is described as a transitional state between normal aging and AD patients. Hence an accurate and reliable diagnosis of MCI can be very effective and helpful for early diagnosis of AD. Therefore in this paper we present a novel and efficient method based on pseudo Zernike moments (PZMs) for the diagnosis of MCI individuals from AD and healthy control (HC) groups using structural MRI. The proposed method uses PZMs to extract discriminative information from the MR images of the AD, MCI, and HC groups. Two types of artificial neural networks, which are based on pattern recognition and learning vector quantization (LVQ) networks, were used to classify the information extracted from the MRIs. We worked with 500 MRIs from the database of the Alzheimer's Disease Neuroimaging Initiative (ADNI 1 1.5T). The 1 slice of 500 MRIs used in this study included 180 AD patients, 172 MCI patients, and 148 HC individuals. We selected 50 percent of the MRIs randomly for use in training the classifiers, 25 percent for validation and we used 25 percent for the testing phase. The technique proposed here yielded the best overall classification results between AD and MCI (accuracy 94.88%, sensitivity 94.18%, and specificity 95.55%), and for pairs of the MCI and HC (accuracy 95.59%, sensitivity 95.89% and specificity 95.34%). These results were achieved using maximum order 30 of PZM and the pattern recognition network with the scaled conjugate gradient (SCG) back propagation training algorithm as a classifier. PMID- 26265553 TI - Processing Cantonese lexical tones: Evidence from oddball paradigms. AB - Two event-related potential (ERP) experiments were conducted to investigate whether Cantonese lexical tones are processed with general auditory perception mechanisms and/or a special speech module. Two tonal features (f0 direction and f0 height deviation) were manipulated to reflect acoustic processing, and the contrast between syllables and hums was used to reveal the involvement of a speech module. Experiment 1 adopted a passive oddball paradigm to study a relatively early stage of tonal processing. Mismatch negativity (MMN) and novelty P3 (P3a) were modulated by the interaction between tonal feature and stimulus type. Similar interactions were found for N2 and P3 in Experiment 2, where more in-depth tonal processing was examined with an active oddball paradigm. Moreover, detecting tonal deviants of syllables elicited N1 and P2 that were not found in hum detection. Together, these findings suggest that the processing of lexical tone relies on both acoustic and linguistic processes from the early stage. Another noteworthy finding is the absence of brain lateralization in both experiments, which challenges the use of a lateralization pattern as evidence for processing lexical tones through a special speech module. PMID- 26265554 TI - Unexpected observation of spatially separated Kondo scattering and ferromagnetism in Ta alloyed anatase TiO2 thin films. AB - We report the observation of spatially separated Kondo scattering and ferromagnetism in anatase Ta0.06Ti0.94O2 thin films as a function of thickness (10-200 nm). The Kondo behavior observed in thicker films is suppressed on decreasing thickness and vanishes below ~25 nm. In 200 nm film, transport data could be fitted to a renormalization group theory for Kondo scattering though the carrier density in this system is lower by two orders of magnitude, the magnetic entity concentration is larger by a similar magnitude and there is strong electronic correlation compared to a conventional system such as Cu with magnetic impurities. However, ferromagnetism is observed at all thicknesses with magnetic moment per unit thickness decreasing beyond 10 nm film thickness. The simultaneous presence of Kondo and ferromagnetism is explained by the spatial variation of defects from the interface to surface which results in a dominantly ferromagnetic region closer to substrate-film interface while the Kondo scattering is dominant near the surface and decreasing towards the interface. This material system enables us to study the effect of neighboring presence of two competing magnetic phenomena and the possibility for tuning them. PMID- 26265555 TI - Changes and roles of membrane compositions in the adaptation of Saccharomyces cerevisiae to ethanol. AB - Bioethanol fermentation by Saccharomyces cerevisiae is often stressed by the accumulation of ethanol. Cell membrane is the first assaulting target of ethanol. Ethanol-adapted S. cerevisiae strains provide opportunity to shed light on membrane functions in the ethanol tolerance. This study aimed at clarifying the roles of cell membrane in the ethanol tolerance of S. cerevisiae through comparing membrane components between S. cerevisiae parental strain and ethanol adapted strains. A directed evolutionary engineering was performed to obtain the ethanol-adapted S. cerevisiae strains. The parental, ethanol-adapted M5 and M10 strains were selected to be compared the percentage of viable cells after exposing to ethanol stress and cell membrane compositions (i.e., ergosterol, trehalose, and fatty acids). Compared with the parental strain, M5 or M10 strain had higher survival rate in the presence of 10% v/v ethanol. Compared with that in the parental strain, contents of trehalose, ergosterol, and fatty acids increased about 15.7, 12.1, and 29.3%, respectively, in M5 strain, and about 47.5, 107.8, and 61.5%, respectively, in M10 strain. Moreover, expression differences of genes involved in fatty acids metabolisms among the parental, M5 and M10 strains were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), and results demonstrated that M5 or M10 strain had higher expression of ACC1 and OLE1 than the parental strain. These results indicated that although being exposed to step-wise increased ethanol, S. cerevisiae cells might remodel membrane components or structure to adapt to the ethanol stress. PMID- 26265556 TI - Evaluating sirolimus-based immunosuppression for the prevention of cytomegalovirus replication after liver transplantation. PMID- 26265557 TI - 2015 ATS conference sleep talks overshadowed by the discussion about ASV negative outcome in heart failure: sleep medicine highlights from the 2015 ATS annual conference in Denver. PMID- 26265558 TI - Serum high-sensitivity C-reactive protein in patients with obstructive sleep apnea with special reference to metabolic syndrome. PMID- 26265559 TI - Comparison of a simple obstructive sleep apnea screening device with standard in laboratory polysomnography. AB - BACKGROUND: Obstructive sleep apnea (OSA) is a common underdiagnosed sleep disorder. Various strategies have been employed to easily screen for OSA. The ApneaStrip(r) (AS - S.L.P. Ltd, Tel Aviv, Israel) is an FDA approved OSA screening device applied to the upper lip at home. We evaluated the performance of this device against simultaneous in-laboratory polysomnography (PSG) in a group of well-characterized OSA patients. METHODS: Diagnostic PSG was performed in 56 patients (29 M, 37 F; age 48.9 +/- 14.6 years; body mass index [BMI] 37.5 +/- 9.0 kg/m(2); apnea-hypopnea index-events/h-[AHI] 32.8 +/- 22.9). The AS was applied and positioned to detect nasal and oral airflow. The AS gives a "positive" result for AHI >= 15. We examined the sensitivity and specificity of the AS against three thresholds derived from PSG: AHI >= 5, AHI >= 15 (company recommendation), and AHI >= 30. RESULTS: For PSG AHI >= 15, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the AS were 80, 54.5, 87.8, and 40 %, respectively. For PSG AHI >= 5, the values were 75.1, 66.7, 97.1, and 13.3 %, respectively. For PSG AHI >= 30, the values were 86.9, 36.2, 48.8, and 80 %, respectively. There were no significant modifying effects of age, BMI, gender, hypertension, diabetes, lung disease, and heart disease. CONCLUSION: The AS has a high sensitivity for detection of OSA with AHI >= 15, but only modest specificity. The AS could be a useful component of an OSA screening program; however, negative results should be interpreted cautiously. PMID- 26265560 TI - A pathway underlying the impact of CPAP adherence on intimate relationship with bed partner in men with obstructive sleep apnea. AB - PURPOSE: Our aim was to determine the pathway underlying the effects of continuous positive airway pressure (CPAP) adherence on intimate relationship with bed partner in men with obstructive sleep apnea (OSA). We hypothesized that CPAP with good adherence affected the intimate relationship with bed partner directly and indirectly, and it was mediated through daytime sleepiness and activity level in men with OSA. METHODS: Data were obtained from an education program for enhancing CPAP adherence. Men who were newly diagnosed of OSA and CPAP therapy naive were recruited in a tertiary teaching hospital. RESULTS: Self reported quality of life [Functional Outcomes of Sleep Questionnaire], daytime sleepiness [Epworth Sleepiness Scale (ESS)], and negative emotion symptoms [depression, anxiety, stress scale] were assessed before and after CPAP treatment at 1-year assessment. Seventy-three men were included in the data analysis, with a mean +/- SD age of 52 +/- 10 years, body mass index of 29.0 +/- 5.2 kg/m(2), ESS of 9.5 +/- 5.6, and median [interquartile range(IR)] apnea and hypopnea index of 31 (21, 56) events/h. The median (IR) CPAP daily usage was 4.3(0, 6.1) h/day. From the path analysis, CPAP therapy was shown to improve intimate relationship directly (beta = 0.185) and indirectly (beta = 0.050) by reducing daytime sleepiness and increasing activity level. However, negative emotion symptoms were not the mediators between CPAP adherence and the intimate relationship. CONCLUSIONS: CPAP therapy with good adherence is related directly and indirectly to a better intimate relationship with bed partner in men with OSA. It was possibly attributed to reduced daytime sleepiness and increased activity level. PMID- 26265561 TI - Developmental windows of susceptibility for epigenetic inheritance through the male germline. AB - Exposure of developing male germ cells to environmental insults has been linked to adverse effects in the offspring. One mechanism by which germ cell defects may be passed intergenerationally is through perturbations in the epigenome at the level(s) of DNA methylation, histone post-translational modifications and/or small non-coding RNAs. Epigenetic programs are particularly dynamic in germ cells undergoing erasure, re-establishment and maintenance of patterns, events potentially susceptible to prenatal and/or postnatal exposures. In this review, we focus on the epigenetic events occurring at each phase of male germ cell development including the prenatal period covering primordial germ cells and prospermatogonia and the postnatal period covering mitotic spermatogonia, meiotic spermatocytes and post-meiotic haploid spermatids and spermatozoa. Strong barriers to the passage of abnormal epigenetic patterns between generations are erected at two times of genome-wide epigenomic reprogramming, first in the germline in primordial germ cells and second, post-fertilization, during preimplantation development. Evidence from high resolution profiling studies that not all epigenetic marks are erased during germ cell and embryonic reprogramming provides a potential explanation for the intergenerational inheritance of abnormal epigenetic marks that may affect offspring health. PMID- 26265562 TI - Knee kinematics and joint moments during gait following anterior cruciate ligament reconstruction: a systematic review and meta-analysis. AB - BACKGROUND: Abnormal gait after anterior cruciate ligament reconstruction (ACLR) may contribute to development and/or progression of knee osteoarthritis. OBJECTIVE: To conduct a systematic review and meta-analysis of knee kinematics and joint moments during walking after ACLR. METHODS: We searched seven electronic databases and reference lists of relevant papers, for cross-sectional, human-based observational studies comparing knee joint kinematics and moments during level walking in individuals with ACLR, with the uninjured contralateral knee or healthy individuals as a control. Two independent reviewers appraised methodological quality (modified Downs and Black scale). Where possible, data were pooled by time post-ACLR (RevMan), otherwise narrative synthesis was undertaken. RESULTS: Thirty-four studies were included. Meta-analysis revealed significant sagittal plane deficits in ACLR knees. We found greater knee flexion angles (standardised mean difference: 1.06; 95% CI 0.39 to 1.74) and joint moments (1.61; 0.87 to 2.35) <6 months post-ACLR, compared to healthy controls. However, lower peak knee flexion angles were identified 1-3 years (-2.21; -3.16 to -1.26) and >=3 years post-ACLR (-1.38, -2.14 to -0.62), and lower knee flexion moment 6-12 months post-ACLR (-0.76; -1.40 to -0.12). Pooled data provided strong evidence of no difference in peak knee adduction moment >3 years after ACLR (vs healthy controls) (0.09; -0.63 to 0.81). No transverse plane conclusions could be drawn. CONCLUSIONS: Sagittal plane biomechanics, rather than the knee adduction moment, appear to be more relevant post-ACLR. Better understanding of sagittal plane biomechanics is necessary for optimal post-operative recovery, and to potentially prevent early onset and progression of knee OA after ACLR. TRIAL REGISTRATION NUMBER: PROSPERO systematic review protocol registration number CRD4201400882 2. PMID- 26265563 TI - Does the presence of placental basal plate myometrial fibres increase the risk of subsequent morbidly adherent placenta: a case-control study. AB - OBJECTIVE: Antenatal diagnosis of morbidly adherent placenta has been shown to improve outcomes, but existing predictors lack sensitivity. Our objective was to determine whether the presence of myometrial fibres attached to the placental basal plate (BPMYO) in an antecedent pregnancy is associated with subsequent morbidly adherent placenta. DESIGN: A case-control study. SETTING: Departments of Obstetrics and Gynecology and Pathology, Northwestern University, Chicago, IL, USA. SAMPLE: Women who had at least two pregnancies with placental pathological evaluation. METHODS: Cases were defined as women with evidence of morbidly adherent placenta (both clinically and pathologically) in their most recent pregnancy whereas women without evidence of morbidly adherent placenta served as controls. Pathological specimens of placentas from previous pregnancies were evaluated for BPMYO. The presence of BPMYO on a previous placenta was evaluated to determine whether it could be used to improve the antenatal diagnosis of morbidly adherent placenta. RESULTS: Of the 25 cases of morbidly adherent placenta, 19 (76%) had BPMYO present on their previous placenta compared with 41 (41%) of controls (odds ratio 4.8, 95% CI 1.8-13.0). Adding BPMYO to a regression including other risk factors for morbidly adherent placenta (i.e. maternal age, number of previous caesarean sections, placenta praevia, previous multiple gestation, any previous curettage, and ultrasonographic suspicion of placenta accreta) significantly improved the sensitivity of antenatal diagnosis of morbidly adherent placenta (61% versus 39%, P < 0.001) without a change in specificity (97% versus 97%, P = 1.00). CONCLUSION: BPMYO on previous placental pathology is associated with an increased risk of morbidly adherent placenta in a subsequent pregnancy. These findings may shed light on the pathophysiology of accreta and inform future research on predictors of accreta. TWEETABLE ABSTRACT: Previous basal plate myometrium improves the ability to detect subsequent morbidly adherent placenta. PMID- 26265565 TI - Lipid labeling from acetate or glycerol in cultured embryos of Camelina sativa seeds: A tale of two substrates. AB - Studies on the metabolism of lipids in seeds frequently use radiolabeled acetate and glycerol supplied to excised developing seeds to track the biosynthesis of acyl and lipid head groups, respectively. Such experiments are generally restricted to shorter time periods and the results may not quantitatively reflect in planta rates. These limitations can be removed by using cultured embryos, provided they mimic growth and lipid deposition observed for embryos in planta. Mid-maturation embryos from Camelina sativa were cultured in vitro to assess the use of sufficient acetate or glycerol concentrations and labeling periods for stable isotope labeling and mass spectrometric detection. Maximum incorporation of exogenous acetate into fatty acids occurred at 1mM and above. This provides about 5% of the total carbon flux entering fatty acids, enough for (13)C isotopomer analysis while maintaining normal biosynthetic rates for over 24h. Labeling analysis indicates that acetate reports lipid metabolism uniformly across the embryo. At higher acetate concentrations with longer incubations, the rate of fatty acid synthesis is reduced and the composition of newly synthesized fatty acids changes. While the mole fractions of oleate that undergo Delta12 desaturation or elongation are independent of biosynthetic flux, Delta15 desaturation shows a bimodal dependence. These observations are consistent with changes occurring in planta over seed development. Incorporation rates of the glyceryl moiety into lipids saturates at about 0.5mM exogenous glycerol. At saturation, the exogenous glycerol almost completely replaces the endogenous supply of glycerol-3-phosphate without affecting net lipid accumulation or fatty acid composition. It is concluded that acetate and glycerol labeling of cultured C. sativa embryos can provide an accurate representation of lipid metabolism in embryos in vivo, and that in Camelina embryos glycerol-3-phosphate levels do not co-limit triacylglycerol synthesis. PMID- 26265566 TI - Co-incidence or causality? Seizures after slow rTMS in stroke patients. PMID- 26265567 TI - Phytochemical Constituents and Biological Activities of Plants from the Genus Dryopteris. PMID- 26265568 TI - On the Quest of Dioxygen by Monomeric Sarcosine Oxidase. A Molecular Dynamics Investigation. AB - It is reported here on random acceleration molecular dynamics (RAMD) simulations with the 2GF3 bacterial monomeric sarcosine oxidase (MSOX), O2 , and furoic acid in place of sarcosine, solvated by TIP3 H2 O in a periodic box. An external tiny force, acting randomly on O2 , accelerated its relocation, from the center of activation between residue K265 and the si face of the flavin ring of the flavin adenine dinucleotide cofactor, to the surrounding solvent. Only three of the four O2 gates previously described for this system along a composite method technique were identified, while two more major O2 gates were found. The RAMD simulations also revealed that the same gate can be reached by O2 along different pathways, often involving traps for O2 . Both the residence time of O2 in the traps, and the total trajectory time for O2 getting to the solvent, could be evaluated. The new quick pathways discovered here suggest that O2 exploits all nearby interstices created by the thermal fluctuations of the protein, not having necessarily to look for the permanent large channel used for uptake of the FADH cofactor. To this regard, MSOX resembles closely KijD3 N-oxygenase. These observations solicit experimental substantiation, in a long term aim at discovering whether gates and pathways for the small gaseous ligands inside the proteins are under Darwinian functional evolution or merely stochastic control operates. PMID- 26265564 TI - Photochemistry and Photobiology of the Spore Photoproduct: A 50-Year Journey. AB - Fifty years ago, a new thymine dimer was discovered as the dominant DNA photolesion in UV-irradiated bacterial spores [Donnellan, J. E. & Setlow R. B. (1965) Science, 149, 308-310], which was later named the spore photoproduct (SP). Formation of SP is due to the unique environment in the spore core that features low hydration levels favoring an A-DNA conformation, high levels of calcium dipicolinate that acts as a photosensitizer, and DNA saturation with small, acid soluble proteins that alters DNA structure and reduces side reactions. In vitro studies reveal that any of these factors alone can promote SP formation; however, SP formation is usually accompanied by the production of other DNA photolesions. Therefore, the nearly exclusive SP formation in spores is due to the combined effects of these three factors. Spore photoproduct photoreaction is proved to occur via a unique H-atom transfer mechanism between the two involved thymine residues. Successful incorporation of SP into an oligonucleotide has been achieved via organic synthesis, which enables structural studies that reveal minor conformational changes in the SP-containing DNA. Here, we review the progress on SP photochemistry and photobiology in the past 50 years, which indicates a very rich SP photobiology that may exist beyond endospores. PMID- 26265569 TI - Phytochemical Analysis, Biological Activity, and Secretory Structures of Stachys annua (L.) L. subsp. annua (Lamiaceae) from Central Italy. AB - Stachys annua subsp. annua, well-known in central Italy as 'stregona annuale', is an annual, small, slightly-scented herb, commonly found in fields and uncultivated areas in almost all regions of Italy. In folk medicine, its aerial parts were used as anti-catarrhal, febrifuge, tonic, and vulnerary. In the present work, the chemical composition of the flowering aerial parts was studied. The hydrodistilled volatile oil, analysed by GC/MS, showed sesquiterpenoids as the major fraction (42.5%); phytol (9.8%), germacrene D (9.2%), and spathulenol (8.5%) were the most abundant constituents. The volatile oil was assayed for antioxidant and cytotoxic activity by DPPH, ABTS, FRAP, and MTT methods. The cytotoxicity results against HCT116, A375, and MDA-MB 231 human tumor cell lines were significant, with IC50 values of 23.5, 37.2, and 41.5 MUg/ml, respectively, whereas the antioxidant power was negligible. The EtOH extract was composed mainly of three glycosidic flavonoids, namely 7-{[2-O-(6-O-acetyl-beta-D allopyranosyl)-beta-D-glucopyranosyl]oxy}-5,8-dihydroxy-2-(4-methoxyphenyl)-4H-1 benzopyran-4-one (1), 7-{[6-O-acetyl-2-O-(6-O-acetyl-beta-D-allopyranosyl)-beta-D glucopyranosyl]oxy}-2-(3,4-dihydroxyphenyl)-5,8-dihydroxy-4H-1-benzopyran-4-one (2), and 7-{[6-O-acetyl-2-O-(beta-D-allopyranosyl)-beta-D-glucopyranosyl]oxy}-2 (3-hydroxy-4-methoxyphenyl)-5,8-dihydroxy-4H-1-benzopyran-4-one (3). On the contrary, iridoids, considered chemotaxonomic markers of the genus Stachys, were absent in this species. Finally, the morphological and histochemical survey showed that glandular trichomes were composed of two main types, i.e. peltate type A and capitate types B and C giving positive response for both lipids and polyphenols. PMID- 26265570 TI - HPTLC and GC/MS Study of Amaryllidaceae Alkaloids of Two Narcissus Species. AB - In this article, we report on the alkaloid profile and dynamic of alkaloid content and diversity in two Narcissus plants at different stages of development. The alkaloid profile of the two Narcissus species was investigated by GC/MS and HPTLC. Fifty eight Amaryllidaceae alkaloids were detected, and 25 of them were identified in the different organs of N. tazetta and N. papyraceus. The alkaloid 3-O-methyl-9-O-demethylmaritidine is tentatively identified here for the first time from the Amaryllidaceae family, and four alkaloids (tazettamide, sternbergine, 1-O-acetyllycorine, 2,11-didehydro-2-dehydroxylycorine) are tentatively identified for the first time in the genus Narcissus. The different organs of the two species analyzed showed remarkable differences in their alkaloid pattern, type of biosynthesis, main alkaloid and number of alkaloids. Lycorine-type alkaloids dominated the alkaloid, metabolism in N. papyraceus, while alkaloids of narciclasine-, galanthamine- and homolycorine-types were found only in the species N. tazetta L. PMID- 26265571 TI - Coleifolides A and B, Two New Sesterterpenoids from the Aerial Parts of Scutellaria coleifolia H.Lev. AB - Coleifolides A and B (1 and 2), two new sesterterpenoids with a beta-methyl alpha,beta-unsaturated-gamma-lactone moiety, were isolated from the aerial parts of Scutellaria coleifolia H.Lev. (Lamiaceae), together with three known compounds. Their structures were elucidated by NMR and MS examinations. Coleifolides A and B were concluded to be partially racemic compounds by the HPLC analysis using a chiral column or introduction of chiral derivatizing agents. The absolute configuration of the major isomer was determined by analyses of the CD spectrum as well as NMR data of (R)- and (S)-2-NMA derivatives. Coleifolides A and B are structurally similar to manoalide derivatives, previously isolated from marine sponges, and appear to be the first examples of this type of compounds being isolated from higher plants. PMID- 26265572 TI - Volatiles as Chemosystematic Markers for Distinguishing Closely Related Species within the Pinus mugo Complex. AB - Headspace solid-phase microextraction (HS-SPME) coupled to GC/MS analysis was used to identify the constituents of pine-needle volatiles differentiating three closely-related pine species within the Pinus mugo complex, i.e., P. uncinata Ramond ex DC., P. uliginosa G.E.Neumann ex Wimm., and P. mugo Turra. Moreover, chemosystematic markers were proposed for the three analyzed pine species. The major constituents of the pine-needle volatiles were alpha-pinene (28.4%) and bornyl acetate (10.8%) for P. uncinata, delta-car-3-ene (21.5%) and alpha-pinene (16.1%) for P. uliginosa, and alpha-pinene (20%) and delta-car-3-ene (18.1%) for P. mugo. This study is the first report on the application of the composition of pine-needle volatiles for the reliable identification of closely-related pine species within the Pinus mugo complex. PMID- 26265573 TI - Diterpene Constituents of Euphorbia exigua L. and Multidrug Resistance Reversing Activity of the Isolated Diterpenes. AB - Phytochemical investigation of the MeOH extract obtained from the aerial parts of the annual weed Euphorbia exigua L. resulted in the isolation of two novel (1, 2) and one known (3) jatrophane diterpenes. Their structures were established by extensive 1D- and 2D-NMR spectroscopy and HR-ESI-MS. The isolated compounds were evaluated for multidrug resistance (MDR) reversing activity on human MDR gene transfected L5178 mouse lymphoma cells; and all three compounds were found to modulate the intracellular drug accumulation. PMID- 26265574 TI - Lupane- and Friedelane-Type Triterpenoids from Celastrus stylosus. AB - Two new triterpenoids, 30-hydroxylup-20(29)-ene 3beta-caffeate (1) and 24-nor friedelan-6alpha,10-dihydroxy-1,2-dioxo-4,7-dien-29-oic acid (2), together with eight known compounds 3-10, were isolated from the roots of Celastrus stylosus. The structures of these compounds were elucidated on the basis of spectroscopic analyses. To the best of our knowledge, this represents the first study on the chemical constituents of C. stylosus. The antiproliferative activities of the triterpenoids against six human cancer cell lines (PANC-1, A549, PC-3, HepG2, SGC 7901, and HCCLM3) were evaluated. Compounds 3, 4, and 10 exhibited comparable activities against PC-3 and HCCLM3 cell lines as the positive control taxol. PMID- 26265575 TI - New Labdane Diterpenes and Their Glycoside Derivatives from the Roots of Isodon adenantha. AB - Two new labdane-type diterpenes (adenanthic acids A and B; 1 and 2, resp.) and three new labdane diterpene glycosides (adenanthosides A-C; 3-5, resp.) were isolated from the roots of Isodon adenantha, together with 23 known constituents including seven diterpenoids (6-12), eight triterpenoids (13-20), one lignan glycoside (21), six steroids (22-27), and one ceramide (28). Their structures were elucidated by spectroscopic methods including extensive 2D-NMR techniques. Cytotoxicity and antibacterial activities of the samples were measured by the MTT method and the filter paper disc agar diffusion method. But none of them showed significant activities. PMID- 26265576 TI - (Chemotaxonomic) Implications of Postharvest/Storage-Induced Changes in Plant Volatile Profiles--the Case of Artemisia absinthium L. Essential Oil. AB - The plant volatile profile and the essential-oil chemical composition change during the storage of plant material. The objective of this study was to develop a mathematical model able to predict, explain, and quantify these changes. Mathematical equations, derived under the assumption that the essential oil contained within plant material could be treated as an ideal solution (Raoult's law), were applied for tracking of postharvest changes in the volatile profile of Artemisia absinthium L. (the essential oils were analyzed by GC-FID and GC/MS). Starting from a specific chemical composition of an essential-oil sample obtained from plant material after a short drying period (typically 5-10 d), and by using the equations derived from this model, one could easily predict evaporation induced changes in the volatile profile of the plant material. Based on the composition of the essential-oil sample obtained after a given storage time t, it is possible to identify those components that were involved in chemical reactions, both as reactants and possible products. The established model even allowed the recognition of pairs of transformation, i.e., 'daughter' products and their 'parent' compounds. The obtained results highlight that the essential-oil composition is highly dependent on the storage period of any plant material and urges caution in different types of phytochemical studies, especially chemotaxonomic ones, or practical application. PMID- 26265577 TI - Three New Isomeric Indole Alkaloids from Nauclea officinalis. AB - Three new isomeric monoterpene indole alkaloids, naucleofficines I-III (1-3, resp.) were isolated from the stems (with bark) of Nauclea officinalis. Their structures were elucidated on the basis of spectroscopic methods and single crystal diffraction analyses. The cytotoxic activities of 1-3 against human colon cancer, human gastric cancer, and human hepatoma cells were also investigated. PMID- 26265578 TI - Biphenyl-Type Neolignan Derivatives from the Twigs of Magnolia denudata and Their Anti-Inflammatory Activity. AB - Two new biphenyl-type neolignan derivatives, 2-[2-(hydroxymethyl)-1-benzofuran-5 yl]-4-(prop-2-en-1-yl)phenol (1) and 2'-ethoxy-5,5'-di(prop-2-en-1-yl)biphenyl-2 ol (2), were isolated from the twigs of Magnolia denudata, together with six known compounds (3-8). The structures of 1 and 2 were determined through extensive 1D- and 2D-NMR and mass-spectrometric analyses. Magnolol (6) and honokiol (7) exhibited potent inhibition (IC50 values=4.4+/-0.2 and 0.71+/-0.13 MUg/ml, resp.) of O$?rm{{_{2}^{{^?cdot} -}}}$ generation by human nutrophils in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB). In addition, 2-[2-(hydroxymethyl)-1-benzofuran-5-yl]-4-(prop-2-en-1 yl)phenol (1), 2'-ethoxy-5,5'-di(prop-2-en-1-yl)biphenyl-2-ol (2), magnolol (6), and vanillic acid (8) inhibited fMLP/CB-induced elastase release with IC50 values=6.4+/-1.5, 2.4+/-0.4, 1.5+/-0.2, and 4.8+/-0.5 MUg/ml, respectively. PMID- 26265579 TI - Fatty-Acid Composition of Seeds and Chemotaxonomic Evaluation of Sixteen Sapindaceae Species. AB - Circumscriptions for the Sapindaceae family and its infrafamilial relationships have been widely discussed. Certain groups are highly morphologically similar; thus, it is difficult to identify certain taxa. DNA Analyses have also indicated complex phylogenetic relationships, and it is difficult to relate such analyses to morphological data. Given the above concerns, this study aimed to investigate the fatty-acid profiles of the seed oils of 16 Sapindaceae species belonging to five tribes and to evaluate their potential chemotaxonomic significance. In total, eleven fatty acids were identified, and eicosenoic acid predominated in nine species. Multivariate analyses (principal component and cluster analyses) of the fatty-acid profiles of the seed oils allowed to separate them in two major clusters. The first cluster, characterized by oils with high eicosenoic acid levels, included all species belonging to the Paullinieae tribe (Cardiospermum, Paullinia, and Serjania species). In the second main cluster, the chemical similarity of the oils was lower, and the species belonged to different tribes. Nevertheless, the tree investigated Allophylus species (Thouinieae tribe) constituted a separate subcluster. Thus, the results showed that the fatty-acid composition of the seed oils of Sapindaceae species provide chemotaxonomic support for the separation of the Paullinieae tribe from the other tribes studied. PMID- 26265580 TI - Five New Guaiane Sesquiterpenes from the Endophytic Fungus Xylaria sp. YM 311647 of Azadirachta indica. AB - Five new guaiane sesquiterpenes, 1-5, were isolated from the culture broth of the endophytic fungus Xylaria sp. YM 311647, isolated from Azadirachta indica A. Juss. The structures of these compounds were elucidated on the basis of spectroscopic analyses, and their inhibitory activities against five pathogenic fungi were evaluated. All guaiane sesquiterpenes showed moderate or weak antifungal activities in a broth microdilution assay. PMID- 26265581 TI - Editorial Comment: Jiangxienone, a New Compound with Potent Cytotoxicity against Tumor Cells from Traditional Chinese Medicinal Mushroom Cordyceps jiangxiensis. PMID- 26265582 TI - Use of faecal occult blood tests in symptomatic patients. PMID- 26265583 TI - Acute chest pain in contingency operations at a Role 1 facility. AB - Acute chest pain is a common medical presenting complaint which can be difficult to diagnose and treat outside of a fully equipped emergency department. In future contingency operations the number of personnel deployed is likely be smaller, with the medical cover appropriate for the population at risk, such that the deployed medical facilities will be smaller than the Role 3 unit with which we have become familiar over the last 10 years of operations in Afghanistan. Physician involvement in these smaller medical facilities is crucial to maintain clinical effect when dealing with patients presenting with disease and non-battle injury, which can often make up the majority of deployed healthcare work. Patients presenting with chest pain require rapid assessment and stabilisation prior to medical evacuation to a suitable definitive care unit. This article focuses on emergency acute chest pain presentations, non-cardiac causes of chest pain, risk reduction and how contingency will affect patient care. PMID- 26265584 TI - Pathophysiological responses to a schistosome infection in a wild population of mourning doves (Zenaida macroura). AB - The blood trematode Gigantobilharzia huronensis typically infects passerine birds and has not been reported in other orders of wild birds. However, in the summer of 2011 in Tempe, Arizona, USA, mourning doves (Zenaida macroura; order: Columbiformes) were collected with infections of G. huronensis. This is the first report of a natural schistosome infection found in wild populations of doves. We sought to determine if G. huronensis infections alter the general body condition and physiology of doves, a seemingly unlikely host for this parasite. Specifically, we hypothesized that birds infected with schistosomes would exhibit reduced weight as well as increased markers of stress and immune system activation. Adult male mourning doves (n=14) were captured using walk-in style funnel traps. After weighing the birds, blood and mesenteric tissue samples were collected. We measured biomarkers of stress including circulating heat shock proteins (HSPs) 60 and 70, as well as oxidized lipoproteins in schistosome infected and non-infected birds. Indices of immune system reactivity were assessed using agglutination and lysis assays in addition to determining the leukocyte to erythrocyte ratios and prevalence of hemoparasite infections from blood smears. Schistosome-infected mourning doves had significantly increased oxidative stress and evidence of HSP70 mobilization. There was no evidence for weight loss in schistosome-infected birds nor evidence of significant immune system activation associated with schistosome infection. This may be a reflection of the small sample size available for the study. These findings suggest that schistosome infections have pathological effects in doves, but the lack of mature worms suggests that infected birds in this sampling may not have been suitable hosts for parasite maturation. PMID- 26265585 TI - Head shape dimorphism in European glass eels (Anguilla anguilla). AB - The life cycle of the European eel (Anguilla anguilla) remained a mystery until the 20th century, when Schmidt discovered that the Sargasso Sea was its spawning area. However, many aspects of the eel's life cycle remain poorly understood. Among these is the bimodal distribution in head shape, with broad- and narrowheaded phenotypes reported in the yellow eel stage. Although this has been linked to dietary preferences of the yellow eels, very little is known about why, how and when this dimorphism arises during their ontogeny. To determine whether this dimorphism indeed appears in relation to trophic niche segregation, we examined head shape variation at an earlier ontogenetic stage, the glass eel stage, as at this stage eels are considered to be non-feeding. Head shape was studied in a large dataset, containing glass eels captured from the Yser river mouth, the Leopold Canal (Belgium) and from the rivers Severn, Trent and Parret (UK), by both taking measurements (head width/head length) and using an outline analysis. Our results show that there is already considerable variation in broadness and bluntness of the head at the glass eel stage. In most cases, equal support for a unimodal and bimodal head shape distribution is found, whereas some cases support head shape bimodality in glass eels, suggesting that glass eel head shape might be shifting from a unimodal to a bimodal distribution. This, in combination with the observation that variation in head width/head length ratios in non-feeding glass eels shows a similar range as in feeding yellow eels, indicates that head shape in European eel might be at least partially determined through other mechanisms than trophic segregation. PMID- 26265586 TI - The estrogenic retina: The potential contribution to healthy aging and age related neurodegenerative diseases of the retina. AB - These last two decades have seen an explosion of clinical and epidemiological research, and basic research devoted to envisage the influence of gender and hormonal fluctuations in the retina/ocular diseases. Particular attention has been paid to age-related disorders because of the overlap of endocrine and neuronal dysfunction with aging. Hormonal withdrawal has been considered among risk factors for diseases such as glaucoma, diabetic retinopathy and age-related macular disease (AMD), as well as, for Alzheimer's disease, Parkinson's disease, or other neurodegenerative disorders. Sex hormones and aging have been also suggested to drive the incidence of ocular surface diseases such as dry eye and cataract. Hormone therapy has been approached in several clinical trials. The discovery that the retina is another CNS tissue synthesizing neurosteroids, among which neuroactive steroids, has favored these studies. However, the puzzling data emerged from clinical, epidemiological and experimental studies have added several dimensions of complexity; the current landscape is inherently limited to the weak information on the influence and interdependence of endocrine, paracrine and autocrine regulation in the retina, but also in the brain. Focusing on the estrogenic retina, we here review our knowledge on local 17beta-oestradiol (E2) synthesis from cholesterol-based neurosteroidogenic path and testosterone aromatization, and presence of estrogen receptors (ERalpha and ERbeta). The first cholesterol-limiting step and the final aromatase-limiting step are discussed as possible check-points of retinal functional/dysfunctional E2. Possible E2 neuroprotection is commented as a group of experimental evidence on excitotoxic and oxidative retinal paradigms, and models of retinal neurodegenerative diseases, such as glaucoma, diabetic retinopathy and AMD. These findings may provide a framework to support clinical studies, although further basic research is needed. PMID- 26265587 TI - Reticulocyte parameters of delta beta thalassaemia trait, beta thalassaemia trait and iron deficiency anaemia. AB - AIMS: To analyse the differences in reticulocyte indices between delta beta thalassaemia trait (deltabeta-TT), beta thalassaemia trait (beta-TT) and iron deficiency anaemia (IDA), and to correlate those differences with the physiopathological features of these three types of microcytoses. METHODS: We performed a descriptive study of 428 samples (43 deltabeta-TT, 179 beta-TT and 206 IDA) that were run on Advia 2120 analyser (Siemens). The following reticulocyte indices were assessed: absolute reticulocyte count (ARC), percentage of reticulocytes, mean corpuscular volume of reticulocytes (MCVr), haemoglobin content of reticulocytes (CHr), mean corpuscular haemoglobin concentration of reticulocytes, red blood cell distribution width of reticulocytes (RDWr), haemoglobin distribution width of reticulocytes (HDWr) and reticulocyte subpopulations based on their fluorescence according to mRNA (low (L-R), medium (M-R) and high (H-R)), MCV ratio and MCHC ratio. Correlation between fetal haemoglobin (HbF) and RDWr in patients with thalassaemia was evaluated. RESULTS: RDWr was significantly higher in deltabeta-TT compared with beta-TT (15.03% vs 13.82%, p<0.001), and so were HDWr (3.65% vs 3.27%, p<0.001), CHr (23.68 vs 22.66 pg, p<0.001) and MCVr (88.3 vs 85.5 fL, p<0.001). A good correlation was observed between HbF and RDWr (r=0.551, p<0.001). IDA subjects have more immature reticulocytes, but less ARC than beta-TT, suggesting a certain degree of inefficient erythropoiesis in IDA in comparison with beta-TT. CONCLUSIONS: Previously described differences between deltabeta-TT, beta-TT and IDA in the corpuscular indices of mature red blood cell can also be observed in reticulocytes. The degree of anisocytosis in reticulocytes from patients with thalassaemia is correlated with HbF. PMID- 26265589 TI - Efficacy of additional psychosocial intervention in reducing low birth weight and preterm birth in teenage pregnancy: A systematic review and meta-analysis. AB - This systematic review aimed to assess the efficacy of psychosocial interventions in reducing risk of low birth weight (LBW) and preterm birth (PTB) in teenage pregnancy. Relevant studies were identified from Medline, Scopus, CINAHL, and CENTRAL databases. Randomized controlled trials investigating effect of psychosocial interventions on risk of LBW and PTB, compared to routine antenatal care (ANC) were eligible. Relative risks (RR) of LBW and PTB were pooled using inverse variance method. Mean differences of birth weight (BW) between intervention and control groups were pooled using unstandardized mean difference (USMD). Five studies were included in the review. Compared with routine ANC, psychosocial interventions significantly reduced risk of LBW by 40% (95%CI: 8%,62%) but not for PTB (pooled RR = 0.67, 95%CI: 0.42,1.05). Mean BW of the intervention group was significantly higher than that of the control group with USMD of 200.63 g (95% CI: 21.02, 380.25). Results of our study suggest that psychosocial interventions significantly reduced risk of LBW in teenage pregnancy. PMID- 26265590 TI - Brief report: A randomized controlled trial examining peer support and behavioral weight loss treatment. AB - Peer support among adolescents has been positively associated with heath behaviors; however, enhancing peer support for weight loss has rarely been studied among adolescents. This study examined whether a peer support training component delivered to enhance a standard weight loss program led to improved outcomes. Forty-one overweight adolescent females were randomly assigned to a Standard or Enhanced Peer Support intervention. The Enhanced group received in person peer support skills training and practiced skills using social networking. At 16 weeks, participants in the Enhanced condition reported significantly increased perceptions of friend support. Both groups demonstrated significant weight loss (6.4 lbs, +/- 8.3). Attendance and self-monitoring were associated with weight loss. Perceptions of peer support can be increased with a peer training component, but did not increase weight loss during the short term. PMID- 26265591 TI - Development and Implementation of CHOICES Group to Reduce Drinking, Improve Contraception, and Prevent Alcohol-Exposed Pregnancies in American Indian Women. AB - Public health officials assert that prevention of alcohol-exposed pregnancies (AEP) should begin before conception, by reducing alcohol consumption in women at risk for or planning pregnancy, and/or preventing pregnancy in women who are drinking at risky levels. One such effort is the Oglala Sioux Tribe (OST) CHOICES Program. While the OST CHOICES Program has been successfully implemented, a community-based needs assessment determined that the OST CHOICES intervention should expand and be delivered in a group setting using group motivational interviewing (MI) techniques. After extensive group MI and CHOICES group trainings, recruitment for CHOICES Group began and within a ten month period, a total of twelve groups with non-pregnant American Indian women were held for this pilot intervention. Evaluations completed by participants indicated that CHOICES Group sessions positively engaged members, had low levels of anger or tension, and had average levels of avoidance of personal responsibility. An evaluation of the CHOICES Group leaders indicated strengths in certain MI skills, although improvement is needed in some core MI and group leadership skills. This is an important expansion of a successful AEP prevention program (CHOICES), as well as a novel application of MI, and recommendations and future plans for this intervention are outlined. PMID- 26265592 TI - Nanoparticle-Loaded Protein-Polymer Nanodroplets for Improved Stability and Conversion Efficiency in Ultrasound Imaging and Drug Delivery. AB - A new formulation of volatile nanodroplets stabilized by a protein and polymer coating and loaded with magnetic nanoparticles is developed. The droplets show enhanced stability and phase conversion efficiency upon ultrasound exposure compared with existing formulations. Magnetic targeting, encapsulation, and release of an anticancer drug are demonstrated in vitro with a 40% improvement in cytotoxicity compared with free drug. PMID- 26265593 TI - Paths and determinants for Penicillium janthinellum to resist low and high copper. AB - Copper (Cu) tolerance was well understood in fungi yeasts but not in filamentous fungi. Filamentous fungi are eukaryotes but unlike eukaryotic fungi yeasts, which are a collection of various fungi that are maybe classified into different taxa but all characterized by growth as filamentous hyphae cells and with a complex morphology. The current knowledge of Cu resistance of filamentous fungi is still fragmental and therefore needs to be bridged. In this study, we characterized Cu resistance of Penicillium janthinellum strain GXCR and its Cu-resistance decreasing mutants (EC-6 and UC-8), and conducted sequencing of a total of 6 transcriptomes from wild-type GXCR and mutant EC-6 grown under control and external Cu. Taken all the results together, Cu effects on the basal metabolism were directed to solute transport by two superfamilies of solute carrier and major facilitator, the buffering free CoA and Acyl-CoA pool in the peroxisome, F type H(+)-transporting ATPases-based ATP production, V-type H(+)-transporting ATPases-based transmembrane transport, protein degradation, and alternative splicing of pre-mRNAs. Roles of enzymatic and non-enzymatic antioxidants in resistance to low and high Cu were defined. The backbone paths, signaling systems, and determinants that involve resistance of filamentous fungi to high Cu were determined, discussed and outlined in a model. PMID- 26265595 TI - Inconsistencies in reporting risk information: a pilot analysis of online news coverage of West Nile Virus. AB - West Nile Virus (WNV) has been reported as one of the worst epidemics in US history. This study sought to understand how WNV news stories were framed and how risk information was portrayed from its 1999 arrival in the US through the year 2012. The authors conducted a quantitative content analysis of online news articles obtained through Google News ( N = 428). The results of this analysis were compared to the CDC's ArboNET surveillance system. The following story frames were identified in this study: action, conflict, consequence, new evidence, reassurance and uncertainty, with the action frame appearing most frequently. Risk was communicated quantitatively without context in the majority of articles, and only in 2006, the year with the third-highest reported deaths, was risk reported with statistical accuracy. The results from the analysis indicated that at-risk communities were potentially under-informed as accurate risks were not communicated. This study offers evidence about how disease outbreaks are covered in relation to actual disease surveillance data. PMID- 26265594 TI - Developmental regulation of planar cell polarity and hair-bundle morphogenesis in auditory hair cells: lessons from human and mouse genetics. AB - Hearing loss is the most common and costly sensory defect in humans and genetic causes underlie a significant proportion of affected individuals. In mammals, sound is detected by hair cells (HCs) housed in the cochlea of the inner ear, whose function depends on a highly specialized mechanotransduction organelle, the hair bundle. Understanding the factors that regulate the development and functional maturation of the hair bundle is crucial for understanding the pathophysiology of human deafness. Genetic analysis of deafness genes in animal models, together with complementary forward genetic screens and conditional knock out mutations in essential genes, have provided great insights into the molecular machinery underpinning hair-bundle development and function. In this review, we highlight recent advances in our understanding of hair-bundle morphogenesis, with an emphasis on the molecular pathways governing hair-bundle polarity and orientation. We next discuss the proteins and structural elements important for hair-cell mechanotransduction as well as hair-bundle cohesion and maintenance. In addition, developmental signals thought to regulate tonotopic features of HCs are introduced. Finally, novel approaches that complement classic genetics for studying the molecular etiology of human deafness are presented. WIREs Dev Biol 2016, 5:85-101. doi: 10.1002/wdev.202 For further resources related to this article, please visit the WIREs website. PMID- 26265596 TI - 'Picture me healthy': a pilot study using photovoice to explore health perceptions among migrant youth in Beijing, China. AB - Globalization has resulted in an influx of migrant families from rural provinces into the urban areas of China. Although the migrant population may live in the same cities as urban residents, they experience different lives because of restricted access to job opportunities, social services, and schools for children. Limited research exists with Chinese rural-to-urban migrant youth, particularly using community-based approaches. This study explored migrant youths' perceptions of their nutrition, physical activity, and health environment, using the community-based participatory research method of photovoice. Twelve migrant youth (6 boys and 6 girls) in Beijing, China, participated in two photovoice assignments focused on personal safety, nutrition, and physical activity. The photographs taken by the youth guided group discussions and semi-structured interviews. Inductive and deductive processes were used to identify codes (ideas emerging from text); similar codes were grouped into themes. Pedestrian safety was the most common personal safety concern. Another safety issue was the excess garbage in the community. Garbage was also a barrier to nutrition and physical activity as it was a food sanitation concern and limited the physical environments where children could play. Schools and community recreation centers were perceived as facilitators of physical activity. However, community centers were also a barrier as a limited number of them caused overcrowding, resulting in safety concerns. Photovoice enables youth to express their health perceptions. Our data provide interesting preliminary insight into the lives of Chinese migrant youth, which could help inform the development of interventions and advocate for positive environmental changes for this marginalized population. PMID- 26265597 TI - Elaboration, characteristics and advantages of biochars for the management of contaminated soils with a specific overview on Miscanthus biochars. AB - Biochars are products that are rich in carbon obtained by pyrolysis processes that consist in introducing a biomass (such as wood or manure) in a closed container and heating it with little or no available air. This paper reports the impacts of pyrolysis parameters on biochar characteristics. A preliminary examination of the scientific literature revealed that the type of feedstock, the temperature, the heating rate and the gas flow were the major parameters influencing the biochar characteristics. This review highlights the multitude of biochars that can be made and shows the importance of characterizing them before their use in soils. Then we assess how the input of biochars in soils can affect soil parameters. A review of the literature showed modifications on: i) the physical properties of soils (i.e. the modification in soil structure and water retention), ii) the chemical properties of soils (i.e. the modification of pH, cation exchange capacity, nutrient availability, the organic matter content) and iii) the biological properties (i.e. the changes in microbial and faunal communities). All these modifications can lead to an increase in crop productivity, which confirms the value of biochars as a soil amendment. Moreover, biochars can also provide an advantage for soil remediation. Indeed, biochars efficiently reduce the bioavailability of organic and inorganic pollutants. In addition, this review focuses on a specific plant that can be used to produce biochars: Miscanthus, a non-wood rhizomatous C4 perennial grass. Miscanthus presents advantages for biochar production due to: i) its lignocellulosic content, ii) its silicon content, which can mitigate environmental stresses (notably for plants grown on contaminated sites) and iii) the greater surface area of the Miscanthus biochars compared to the biochars produced with other feedstock. PMID- 26265598 TI - Spray drift reduction techniques for vineyards in fragmented landscapes. AB - In intensive agricultural systems spray drift is one of the major potential diffuse pollution pathways for pesticides and poses a risk to the environment. There is also increasing concern about potential exposure to bystanders and passers-by, especially in fragmented landscapes like the Italian pre-Alps, where orchards and vineyards are surrounded by residential houses. There is thus an urgent need to do field measurements of drift generated by air-blast sprayer in vineyards, and to develop measures for its reduction (mitigation). A field experiment with an "event method" was conducted in north-eastern Italy in no-wind conditions, in the hilly area famed for Prosecco wine production, using an air blast sprayer in order to evaluate the potential spray drift from equipment and the effectiveness of some practical mitigation measures, either single or in combination. A definition of mitigation is proposed, and a method for the calculation of total effectiveness of a series of mitigation measures is applied to some what-if scenarios of interest. Results show that low-drift equipment reduced potential spray drift by 38% and that a fully developed vine curtain mitigated it by about 70%; when the last row was treated without air-assistance mitigation was about 74%; hedgerows were always very effective in providing mitigation of up to 98%. In conclusion, spray drift is not inevitable and can be markedly reduced using a few mitigation measures, most already available to farmers, that can be strongly recommended for environmental regulatory schemes and community-based participatory research. PMID- 26265599 TI - Improved waste water treatment by bio-synthesized Graphene Sand Composite. AB - The photocatalytic and antibacterial properties of graphene biosynthesized from sugar and anchored on sand particles has been focused here. The morphology and composition of the synthesized Graphene Sand Composite (GSC) was investigated by means of X-ray powder diffraction (XRD), Scanning Electron Microscopy (SEM), Energy Dispersive X-Ray Spectroscopy (EDAX), Fourier Transform Infra-red Spectroscopy (FTIR) and UV-Visible spectroscopy. SEM images show wrinkly edges. This is characteristic of graphenic morphology. Three types of waste water samples namely, textile waste (TW), sugarcane industrial waste water (SW) and domestic waste water from a local purification center at Kodaikanal (KWW) were collected and treated. Adsorption experiments showed effective removal of impurities at 0.2 g of GSC. Photocatalytic activity was analyzed under visible and ultraviolet irradiation. The rate constant for TW increased to 0.0032/min for visible light irradiation from 0.0029/min under UV irradiation. SW showed similar improved activity with rate constant as 0.0023/min in visible irradiation compared to 0.0016/min under UV irradiation. For KWW enhanced activity was seen only in visible light irradiation with rate constant 0.0025/min. GSC showed an inhibition zone of 20 mm against the bacterium Escherichia coli. Results suggest development of economic and effective waste water management systems. PMID- 26265600 TI - Arsenic and fluoride contaminated groundwaters: A review of current technologies for contaminants removal. AB - Chronic contamination of groundwaters by both arsenic (As) and fluoride (F) is frequently observed around the world, which has severely affected millions of people. Fluoride and As are introduced into groundwaters by several sources such as water-rock interactions, anthropogenic activities, and groundwater recharge. Coexistence of these pollutants can have adverse effects due to synergistic and/or antagonistic mechanisms leading to uncertain and complicated health effects, including cancer. Many developing countries are beset with the problem of F and As laden waters, with no affordable technologies to provide clean water supply. The technologies available for the simultaneous removal are akin to chemical treatment, adsorption and membrane processes. However, the presence of competing ions such as phosphate, silicate, nitrate, chloride, carbonate, and sulfate affect the removal efficiency. Highly efficient, low-cost and sustainable technology which could be used by rural populations is of utmost importance for simultaneous removal of both pollutants. This can be realized by using readily available low cost materials coupled with proper disposal units. Synthesis of inexpensive and highly selective nanoadsorbents or nanofunctionalized membranes is required along with encapsulation units to isolate the toxicant loaded materials to avoid their re-entry in aquifers. A vast number of reviews have been published periodically on removal of As or F alone. However, there is a dearth of literature on the simultaneous removal of both. This review critically analyzes this important issue and considers strategies for their removal and safe disposal. PMID- 26265601 TI - Adsorption removal of antiviral drug oseltamivir and its metabolite oseltamivir carboxylate by carbon nanotubes: Effects of carbon nanotube properties and media. AB - This investigation evaluated the adsorption behavior of the antiviral drugs of oseltamivir (OE) and its metabolites (i.e., oseltamivir carboxylate (OC)) on three types of carbon nanotubes (CNTs) including single-walled CNT (SWCNT), multi walled CNT (MWCNT), and carboxylated SWCNT (SWCNT-COOH). CNTs can efficiently remove more than 90% of the OE and OC from aqueous solution when the initial concentration was lower than 10(-4) mmol/L. The Polanyi-Manes model depicted the adsorption isotherms of OE and OC on CNTs better than the Langmuir and Freundlich models. The properties of OE/OC and the characteristics of CNTs, particularly the oxygen functional groups (e.g., SWCNT-COOH) played important roles during the adsorption processes. OE showed a higher adsorption affinity than OC. By comparing the different adsorbates adsorption on each CNT and each adsorbate adsorption on different CNTs, the adsorption mechanisms of hydrophobic interaction, electrostatic interaction, van der Waals force, and H-bonding were proposed as the contributing factors for OE and OC adsorption on CNTs. Particularly, for verifying the contribution of electrostatic interaction, the changes of adsorption partition efficiency (Kd) of OE and OC on CNTs were evaluated by varying pH from 2 to 11 and the importance of isoelectric point (pHIEP) of CNTs on OE and OC adsorption was addressed. PMID- 26265602 TI - From the Neonatal Resuscitation Program to Helping Babies Breathe: Global impact of educational programs in neonatal resuscitation. AB - Two educational programs in neonatal resuscitation, the Neonatal Resuscitation Program (NRP) and Helping Babies Breathe (HBB) have found widespread acceptance globally as practical tools to improve newborn survival and reduce death from perinatal asphyxia. The programs share a common scientific evidence base and both employ adult education principles with an emphasis on building skills. However, they differ in their target audience and context, their core content, and the methods used for knowledge translation. This review describes how the design of NRP transported it outside the USA to countries around the globe and how the program has contributed to improvements in care at multiple levels from the bedside to guidelines and research. It examines the gaps in the reach of NRP that stimulated the development of HBB and helped shape a different approach to education of health care providers in resource-limited settings. Implementation of HBB is summarized to date, and evidence provided of its effectiveness in reducing neonatal death and stillbirth. Finally, consideration of how the programs function together suggests their future potential to strengthen health systems and maximize the impact on the health of newborns. PMID- 26265603 TI - Silent War to Emerging or Re-emerging Respiratory Infection Diseases Badly Kept in Mind. PMID- 26265604 TI - A Nomogram for Predicting the Likelihood of Obstructive Sleep Apnea to Reduce the Unnecessary Polysomnography Examinations. AB - BACKGROUND: The currently available polysomnography (PSG) equipments and operating personnel are facing increasing pressure, such situation may result in the problem that a large number of obstructive sleep apnea (OSA) patients cannot receive timely diagnosis and treatment, we sought to develop a nomogram quantifying the risk of OSA for a better decision of using PSG, based on the clinical syndromes and the demographic and anthropometric characteristics. METHODS: The nomogram was constructed through an ordinal logistic regression procedure. Predictive accuracy and performance characteristics were assessed with the area under the curve (AUC) of the receiver operating characteristics and calibration plots, respectively. Decision curve analyses were applied to assess the net benefit of the nomogram. RESULTS: Among the 401 patients, 73 (18.2%) were diagnosed and grouped as the none OSA (apnea-hypopnea index [AHI] <5), 67 (16.7%) the mild OSA (5 <= AHI < 15), 82 (20.4%) the moderate OSA (15 <= AHI < 30), and 179 (44.6%) the severe OSA (AHI >= 30). The multivariable analysis suggested the significant factors were duration of disease, smoking status, difficulty of falling asleep, lack of energy, and waist circumference. A nomogram was created for the prediction of OSA using these clinical parameters and was internally validated using bootstrapping method. The discrimination accuracies of the nomogram for any OSA, moderate-severe OSA, and severe OSA were 83.8%, 79.9%, and 80.5%, respectively, which indicated good calibration. Decision curve analysis showed that using nomogram could reduce the unnecessary polysomnography (PSG) by 10% without increasing the false negatives. CONCLUSIONS: The established clinical nomogram provides high accuracy in predicting the individual risk of OSA. This tool may help physicians better make decisions on PSG arrangement for the patients referred to sleep centers. PMID- 26265605 TI - Presence of Fragmented QRS Complexes in Patients with Obstructive Sleep Apnea Syndrome. AB - BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is a disease with increasing prevalence, which is mainly characterized by increased cardiopulmonary mortality and morbidity. It is well-known that OSAS patients have increased prevalence of cardiovascular diseases including coronary heart disease, heart failure, and arrhythmias. The aim of this study was to evaluate the presence of prolonged and fragmented QRS complexes, which have previously been associated with cardiovascular mortality, in OSAS patients. METHODS: Our study included 51 patients (mean age 41.6 +/- 10.1 years) who were recently diagnosed with OSAS (apnea-hypopnea index [AHI] >=5 events/h) and never received therapy. The control group consisted of 34 volunteers (mean age 43.1 +/- 11.6 years) in whom OSAS was excluded (AHI <5 events/h). The longest QRS complexes was measured in the 12-lead electrocardiogram (ECG) and the presence of fragmentation in QRS complexes was investigated. RESULTS: Fragmented QRS frequency was significantly higher in patients with OSAS (n = 31 [61%] vs. n = 12 [35%], P = 0.021). QRS and QTc durations were also significantly longer in OSAS patients than controls (99.8 +/- 13.9 ms vs. 84.7 +/- 14.3 ms, P < 0.001; 411.4 +/- 26.9 ms vs. 390.1 +/- 32.2 ms, P = 0.001, respectively). Analysis of the patient and controls groups combined revealed a weak-moderate correlation between AHI and QRS duration (r = 0.292, P = 0.070). OSAS group had no correlation between AHI and QRS duration (r = -0.231, P = 0.203). CONCLUSIONS: In our study fragmented QRS frequency and QRS duration were found to increase in OSAS patients. Both parameters are related with increased cardiovascular mortality. Considering the prognostic importance of ECG parameters, it may be reasonable to recommend more detailed evaluation of OSAS patients with fragmented or prolonged QRS complexes with respect to presence of cardiovascular diseases. PMID- 26265606 TI - Obstructive Sleep Apnea Hypopnea Syndrome as a Reason for Active Management of Pulmonary Embolism. AB - BACKGROUND: Obstructive sleep apnea hypopnea syndrome (OSAHS) constitutes an independent factor for high warfarin dose for patients with pulmonary embolism (PE). The aim of this study was to investigate whether the 6-month anticoagulation treatment by warfarin is enough for patients with PE complicated by OSAHS. METHODS: We investigated 97 PE patients, 32 of them had OSAHS and 65 non-OSAHS. Warfarin was administered for 6-month if no abnormal circumstances occurred. All patients were followed up for 18 months. Adverse events (AE) included death, major bleeding, hospitalization due to heart failure or pulmonary hypertension, and recurrence or aggravation of PE (including deep vein thrombosis). Recurrence rate of PE after warfarin cessation was compared between the two groups. RESULTS: OSAHS patients required a significantly higher dose of warfarin than their non-OSAHS counterparts (4.73 mg vs. 3.61 mg, P < 0.001). During warfarin treatment, no major bleeding and aggravation of PE occurred among OSAHS patients, and the rates of various AE were not significantly different between the OSAHS and non-OSAHS groups. PE recurrence was higher in OSAHS than non-OSAHS groups after withdrawal of warfarin (21.43% vs. 6.78%, P = 0.047). Compared with non-OSAHS patients, OSAHS group had lower international normalized ratio (INR) value but higher plasminogen on baseline and INR resumed to a relatively low level after warfarin discontinuation. CONCLUSIONS: OSAHS patients may present with hypercoagulation and relatively high-risk of recurrence of PE after cessation of 6-month warfarin treatment. PMID- 26265607 TI - Nonstent Combination Interventional Therapy for Treatment of Benign Cicatricial Airway Stenosis. AB - BACKGROUND: Benign cicatricial airway stenosis (BCAS) is a life-threatening disease. While there are numerous therapies, all have their defects, and stenosis can easily become recurrent. This study aimed to investigate the efficacy and complications of nonstent combination interventional therapy (NSCIT) when used for the treatment of BCAS of different causes and types. METHODS: This study enrolled a cohort of patients with BCAS resulting from tuberculosis, intubation, tracheotomy, and other origins. The patients were assigned to three groups determined by their type of stenosis: Web-like stenosis, granulation stenosis, and complex stenosis, and all patients received NSCIT. The efficacy and complications of treatment in each group of patients were observed. The Chi square test, one-factor analysis of variance (ANOVA), and the paired t -test were used to analyze different parameters. RESULTS: The 10 patients with web-like stenosis and six patients with granulation stenosis exhibited durable remission rates of 100%. Among 41 patients with complex stenosis, 36 cases (88%) experienced remission and 29 cases (71%) experienced durable remission. When five patients with airway collapse were eliminated from the analysis, the overall remission rate was 97%. The average treatment durations for patients with web like stenosis, granulation stenosis, and complex stenosis were 101, 21, and 110 days, respectively, and the average number of treatments was five, two, and five, respectively. CONCLUSIONS: NSCIT demonstrated good therapeutic efficacy and was associated with few complications. However, this approach was ineffective for treating patients with airway collapse or malacia. PMID- 26265608 TI - Esophageal Functional Changes in Obstructive Sleep Apnea/Hypopnea Syndrome and Their Impact on Laryngopharyngeal Reflux Disease. AB - BACKGROUND: Obstructive sleep apnea/hypopnea syndrome (OSAHS) and laryngopharyngeal reflux (LPR) disease have a high comorbidity rate, but the potential causal relation between the two diseases remains unclear. Our objectives were to investigate the esophageal functional changes in OSAHS patients and determine whether OSAHS affects LPR by affecting esophageal functions. METHODS: Thirty-six OSAHS patients and 10 healthy controls underwent 24-h double-probed combined esophageal multichannel intraluminal impedance and pH monitoring simultaneously with polysomnography. High-resolution impedance manometry was applied to obtain a detailed evaluation of pharyngeal and esophageal motility. RESULTS: There were 13 OSAHS patients (36.1%) without LPR (OSAHS group) and 23 (63.9%) with both OSAHS and LPR (OSAHS and LPR group). Significant differences were found in the onset velocity of liquid swallows (OVL, P = 0.029) and the percent relaxation of the lower esophageal sphincter (LES) during viscous swallows (P = 0.049) between the OSAHS and control groups. The percent relaxation of LES during viscous swallows was found to be negatively correlated with upright distal acid percent time (P = 0.016, R = -0.507), and OVL was found to be negatively correlated with recumbent distal acid percent time (P = 0.006, R = -0.557) in the OSAHS and LPR group. CONCLUSIONS: OSAHS patients experience esophageal functional changes, and linear correlations were found between the changed esophageal functional parameters and reflux indicators, which might be the reason that LPR showed a high comorbidity with OSAHS and why the severity of the two diseases is correlated. PMID- 26265609 TI - P2X7 Receptor Antagonism Attenuates the Intermittent Hypoxia-induced Spatial Deficits in a Murine Model of Sleep Apnea Via Inhibiting Neuroinflammation and Oxidative Stress. AB - BACKGROUND: The mechanism of the neural injury caused by chronic intermittent hypoxia (CIH) that characterizes obstructive sleep apnea syndrome (OSAS) is not clearly known. The purpose of this study was to investigate whether P2X7 receptor (P2X7R) is responsible for the CIH-induced neural injury and the possible pathway it involves. METHODS: Eight-week-old male C57BL/6 mice were used. For each exposure time point, eight mice divided in room air (RA) and IH group were assigned to the study of P2X7R expression. Whereas in the 21 days-Brilliant Blue G (BBG, a selective P2X7R antagonist) study, 48 mice were randomly divided into CIH group, BBG-treated CIH group, RA group and BBG-treated RA group. The hippocampus P2X7R expression was determined by Western blotting and real-time polymerase chain reaction (PCR). The spatial learning was analyzed by Morris water maze. The nuclear factor kappa B (NFkappaB) and NADPH oxidase 2 (NOX2) expressions were analyzed by Western blotting. The expressions of tumor necrosis factor alpha, interleukin 1beta (IL-beta), IL-18, and IL-6 were measured by real time PCR. The malondialdehyde and superoxide dismutase levels were detected by colorimetric method. Cell damage was evaluated by Hematoxylin and Eosin staining and Terminal Transferase dUTP Nick-end Labeling method. RESULTS: The P2X7R mRNA was elevated and sustained after 3-day IH exposure and the P2X7R protein was elevated and sustained after 7-day IH exposure. In the BBG study, the CIH mice showed severer neuronal cell damage and poorer performance in the behavior test. The increased NFkappaB and NOX2 expressions along with the inflammation injury and oxidative stress were also observed in the CIH group. BBG alleviated CIH induced neural injury and consequent functional deficits. CONCLUSIONS: The P2X7R antagonism attenuates the CIH-induced neuroinflammation, oxidative stress, and spatial deficits, demonstrating that the P2X7R is an important therapeutic target in the cognition deficits accompanied OSAS. PMID- 26265610 TI - Predictive Ability of the SYNergy Between Percutaneous Coronary Intervention with TAXus and Cardiac Surgery Score II for Long-term Mortality in Patients with Three vessel Coronary Artery Disease Undergoing Percutaneous Coronary Intervention Treated with Second-generation Drug-eluting Stents. AB - BACKGROUND: The SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery Score II (SS-II) can well predict 4-year mortality in patients with complex coronary artery disease (CAD), and guide decision-making between coronary artery bypass graft surgery and percutaneous coronary intervention (PCI). However, there is lack of data regarding the utility of the SS-II in patients with three-vessel CAD undergoing PCI treated with second-generation drug eluting stents (DES). The purpose of the present study was to evaluate the ability of the SS-II to predict long-term mortality in patients with three-vessel CAD undergoing PCI with second-generation DES. METHODS: Totally, 573 consecutive patients with de novo three-vessel CAD who underwent PCI with second-generation DES were retrospectively studied. According to the tertiles of the SS-II, the patients were divided into three groups: The lowest SS-II tertile (SS-II <=20), intermediate SS-II tertile (SS-II of 21-31), and the highest SS-II tertile (SS-II >=32). The survival curves of the different groups were estimated by the Kaplan Meier method. Univariate and multivariate Cox proportional hazard regression analyses were performed to evaluate the relationship between the SS-II and 5-year mortality. The performance of the SS-II with respect to predicting the rate of mortality was studied by calculating the area under the receiver operator characteristic (ROC) curve. The predictive ability of the SS-II for 5-year mortality was evaluated and compared with the SS alone. RESULTS: The overall SS II was 27.6 +/- 9.0. Among patients in the lowest, intermediate and the highest SS-II tertiles, the 5-year rates of mortality were 1.6%, 3.2%, and 8.6%, respectively (P = 0.003); the cardiac mortality rates were 0.5%, 1.9%, and 5.2%, respectively (P = 0.014). By multivariable analysis, adjusting for the potential confounders, the SS-II was an independent predictor of 5-year mortality (hazard ratio: 2.45, 95% confidence interval: 1.38-4.36; P = 0.002). The SS-II demonstrated a higher predictive accuracy for 5-year mortality compared with the SS alone (the area under the ROC curve was 0.705 and 0.598, respectively). CONCLUSION: The SS-II is an independent predictor of 5-year mortality in patients with three-vessel CAD undergoing PCI treated with second-generation DES, and demonstrates a superior predictive ability over the SS alone. PMID- 26265611 TI - CYP2C19*2 and Other Allelic Variants Affecting Platelet Response to Clopidogrel Tested by Thrombelastography in Patients with Acute Coronary Syndrome. AB - BACKGROUND: To investigate the contributions of CYP2C19 polymorphisms to the various clopidogrel responses tested by thrombelastography (TEG) in Chinese patients with the acute coronary syndrome (ACS). METHODS: Patients were screened prospectively with ACS diagnose and were treated with clopidogrel and aspirin dual antiplatelet therapy. CYP2C19 loss of function (LOF) and gain of function (GOF) genotype, adenosine 5'-diphosphate (ADP)-channel platelet inhibition rate (PIR) tested by TEG and the occurrence of 3-month major adverse cardiovascular events and ischemic events were assessed in 116 patients. RESULTS: High on treatment platelet reactivity (HTPR) prevalence defined by PIR <30% by TEG in ADP channel was 32.76% (38/116). With respect to the normal wild type, CYP2C19*2, and *3 LOF alleles, and *17 GOF alleles, patients were classified into three metabolism phenotypes: 41.38% were extensive metabolizers (EMs), 56.90% were intermediate metabolizers (IMs), and 1.72% were poor metabolizers (PMs). Of the enrolled patients, 31.47%, 5.17%, and 0.43%, respectively, were carriers of *2, *3, and *17 alleles. The HTPR incidence differed significantly according to CYP2C19 genotypes, accounting for 18.75%, 41.54%, and 100.00% in EMs, IMs, and PMs, respectively. Eighteen (17.24%) ischemic events occurred during the 3-month follow-up, and there was a significant difference in ischemic events between HTPR group and nonhigh on-treatment platelet reactivity group. CONCLUSIONS: Genetic CYP2C19 polymorphisms are relative to the inferior, the antiplatelet activity after clopidogrel admission and may increase the incidence of ischemic events in patients with ACS. PMID- 26265612 TI - A Marked Increase in Obstetric Hysterectomy for Placenta Accreta. AB - BACKGROUND: Obstetric hysterectomy (OH) as a lifesaving measure to manage uncontrolled uterine hemorrhage appears to be increasing recently. The objective of this study was to determine the etiology and changing trends of OH and to identify those at particular risk of OH to enhance the early involvement of multidisciplinary intensive care. METHODS: A retrospective study was carried out in patients who had OH in China-Japan Friendship Hospital from 2004 to 2014. Maternal characteristics, preoperative evaluation, operative reports, and prenatal outcomes were studied in detail. RESULTS: There were 19 cases of OH among a total of 18,838 deliveries. Comparing the study periods between 2004-2010 and 2011-2014, OH increased from 0.8/1000 (10/12,890) to 1.5/1000 (9/5948). Indications for OH have changed significantly during this study period with uterine atony decreasing from 50.0% (5/10) to 11.1% (1/9) (P < 0.05), and placenta accreta as the indication for OH has increased significantly from 20.0% (2/10) to 77.8% (7/9) (P < 0.05). Ultrasonography and magnetic resonance imaging (MRI) have been used to make an exact antepartum diagnosis of placenta accreta. A multidisciplinary management led to improved outcomes for patients with placenta accreta. CONCLUSION: As the multiple cesarean delivery rates have risen, there has been a dramatic increase in OH for placenta accreta. An advance antenatal diagnosis of ultrasonography, and MRI, and a multidisciplinary teamwork can maximize patients' safety and outcome. PMID- 26265613 TI - Comparison of Therapeutic Efficacy between Gastrectomy with Transarterial Chemoembolization Plus Systemic Chemotherapy and Systemic Chemotherapy Alone in Gastric Cancer with Synchronous Liver Metastasis. AB - BACKGROUND: Systemic chemotherapy (SC) is the recommended treatment for gastric cancer with liver metastasis. However, the improvement in survival has been disappointing. The aim of this study was to compare the therapeutic efficacy of gastrectomy with transarterial chemoembolization plus SC (GTC) and SC alone for gastric cancer with synchronous liver metastasis. METHODS: From January 2008 to December 2013, 107 gastric cancer patients with synchronous liver metastasis attending the four participating centers were enrolled in this multicenter, ambispective, controlled cohort study. Patients who underwent GTC (n = 32) were compared with controls who were received SC alone (n = 75). The primary endpoints of the study were overall survival (OS) and progression-free survival (PFS). The secondary endpoints were response rate to treatment and treatment-related adverse effects. RESULTS: The median OS was 14.0 months (95% confidence interval [CI ]: 13.1-14.9 months) in the GTC treatment group and 8.0 months (95% CI : 6.6-9.4 months) in SC group, this difference being statistically significant (P < 0.001). The median PFS was significantly longer in the GTC than in the SC group (5 months, 95% CI : 2.2-7.8 months vs. 3 months, 95% CI : 2.3-3.4 months, respectively) (P < 0.001). The rate of response to treatment was significantly better in the GTC than the SC group (59.4% vs. 37.4%, respectively) (P = 0.035). According to multivariate analysis, OS in patients receiving combination treatment was significantly correlated with the size (P = 0.037) and extent of liver metastases (P < 0.001). PFS was also correlated with the extent of liver metastases (P = 0.003). CONCLUSIONS: GTC is more effective than SC alone in patients with gastric cancer with synchronous liver metastasis. GTC therapy prolongs the survival of selected gastric cancer patients with synchronous liver metastasis. PMID- 26265614 TI - Home-based Early Intervention on Auditory and Speech Development in Mandarin speaking Deaf Infants and Toddlers with Chronological Aged 7-24 Months. AB - BACKGROUND: Early auditory and speech development in home-based early intervention of infants and toddlers with hearing loss younger than 2 years are still spare in China. This study aimed to observe the development of auditory and speech in deaf infants and toddlers who were fitted with hearing aids and/or received cochlear implantation between the chronological ages of 7-24 months, and analyze the effect of chronological age and recovery time on auditory and speech development in the course of home-based early intervention. METHODS: This longitudinal study included 55 hearing impaired children with severe and profound binaural deafness, who were divided into Group A (7-12 months), Group B (13-18 months) and Group C (19-24 months) based on the chronological age. Categories auditory performance (CAP) and speech intelligibility rating scale (SIR) were used to evaluate auditory and speech development at baseline and 3, 6, 9, 12, 18, and 24 months of habilitation. Descriptive statistics were used to describe demographic features and were analyzed by repeated measures analysis of variance. RESULTS: With 24 months of hearing intervention, 78% of the patients were able to understand common phrases and conversation without lip-reading, 96% of the patients were intelligible to a listener. In three groups, children showed the rapid growth of trend features in each period of habilitation. CAP and SIR scores have developed rapidly within 24 months after fitted auxiliary device in Group A, which performed much better auditory and speech abilities than Group B (P < 0.05) and Group C (P < 0.05). Group B achieved better results than Group C, whereas no significant differences were observed between Group B and Group C (P > 0.05). CONCLUSIONS: The data suggested the early hearing intervention and home-based habilitation benefit auditory and speech development. Chronological age and recovery time may be major factors for aural verbal outcomes in hearing impaired children. The development of auditory and speech in hearing impaired children may be relatively crucial in thefirst year's habilitation after fitted with the auxiliary device. PMID- 26265615 TI - Rib Cartilage Assessment Relative to the Healthy Ear in Young Children with Microtia Guiding Operative Timing. AB - BACKGROUND: The optimal age at which to initiate for auricular reconstruction is controversial. Rib cartilage growth is closely related to age and determines the feasibility and outcomes of auricular reconstruction. We developed a method to guide the timing of auricular reconstruction in children with microtia ranging in age from 5 to 10 years. METHODS: Rib cartilage and the healthy ear were assessed using low-dose multi-slice computed tomography. The lengths of the eighth rib cartilage and the helix of the healthy ear (from the helical crus to the joint of the helix and the earlobe) were measured. Surgery was performed when the two lengths were approximately equal. RESULTS: The preoperative eighth rib measurements significantly correlated with the intraoperative measurements (P < 0.05). From 5 to 10 years of age, eighth rib growth was not linear. In 76 (62.8%) of 121 patients, the eighth rib length was approximately equal to the helix length in the healthy ear; satisfactory outcomes were achieved in these patients. In 18 (14.9%) patients, the eighth rib was slightly shorter than the helix, helix fabrication was accomplished by adjusting the length of the helical crus of stent, and satisfactory outcomes were also achieved. Acceptable outcomes were achieved in 17 (14.0%) patients in whom helix fabrication was accomplished by cartilage splicing. In 9 (7.4%) patients with insufficient rib cartilage length, the operation was delayed. In one (0.8%) patient with insufficient rib cartilage length, which left no cartilage for helix splicing, the result was unsatisfactory. CONCLUSIONS: Eighth rib cartilage growth is variable. Rib cartilage assessment relative to the healthy ear can guide auricular reconstruction and personalize treatment in young patients with microtia. PMID- 26265616 TI - Follow-up of N400 in the Rehabilitation of First-episode Schizophrenia. AB - BACKGROUND: The N400 component of event-related potentials (ERP) has recently drawn widespread attention at home and abroad. This study was to explore the relationship between N400 changes and risperidone treatment and rehabilitation infirst-episode schizophrenia (FES). METHODS: ERP component N400 was recorded by Guangzhou Runjie WJ-1 ERP instruments, in 58 FES before and 6 months, 15 months after risperidone treatment, and in 62 normal controls. The patients' syndromes were assessed by Positive and Negative Syndrome Scale (PANSS). And the stimuli are Chinese sentences with matching (congruent) or mismatching (incongruent) ending words. RESULTS: N400 latencies were prolonged, and amplitudes were decreased in Cz, Pz, Fz, C3, C4, in FES compared with in NC, before treatment. The prolonged N400 latencies and decreased amplitudes were negatively correlated with the patients' positive scale and total scale of PANSS. There are significant differences of N400 amplitudes and latencies in 6 months and 15 months follow-up after treatment. Before treatment, 6 months and 15 months after treatment, N400 latencies are 446 +/- 35 ms, 440 +/- 37 ms, 414 +/- 31 ms (F = 9.72, P < 0.01) in incongruent situation; N400 amplitudes are 5.2 +/- 4.6 MUV, 5.7 +/- 4.8 MUV, 7.3 +/- 5.0 MUV (F = 2.06, P > 0.05) in congruent situation, and 8.5 +/- 5.9 MUV, 10.1 +/- 5.0 MUV, 11.9 +/- 7.0 MUV (F = 3.697, P < 0.05) in incongruent situation. CONCLUSIONS: N400 could be used to predict the effects of treatment of schizophrenia to some degree. The linguistic and cognitive impairment in schizophrenia can be improved by antipsychotic drugs. PMID- 26265617 TI - Reduction of Glucose Metabolism in Olfactory Bulb is an Earlier Alzheimer's Disease-related Biomarker in 5XFAD Mice. AB - BACKGROUND: Early diagnosis assumes a vital role in an effective treatment of Alzheimer's disease (AD). Most of the current studies can only make an AD diagnosis after the manifestation of typical clinical symptoms. The present study aimed to investigate typical and other biomarkers of AD to find a possible early biomarker. METHODS: A total of 14 5XFAD mice (at 3 and 6 months old), with 14 age matched wild-type (WT) mice as control, were enrolled in this case-control study. Morris water maze test was performed to evaluate the cognitive function; buried food pellet test and olfactory maze test were employed to investigate the olfactory function; immunofluorescence to detect amyloid deposition and positron emission tomography to examine 2-deoxy-2-(18F) fluoro-D-glucose ([18F]-FDG) uptake in the hippocampus and cerebral cortex. RESULTS: With the increasing age, cognitive performance (P = 0.0262) and olfactory function were significantly deteriorated (day 1 P = 0.0012, day 2 P = 0.0031, day 3 P = 0.0160, respectively) and the (18F)-FDG uptake was markedly decreased in multi-cerebral regions including the olfactory bulb (P < 0.0001), hippocampus (P = 0.0121), and cerebral cortex (P < 0.0001). Of note, in 3-month-old 5XFAD mice, a significant decline of (18F)-FDG uptake in the olfactory bulb was found when compared with that of age matched WT mice (P = 0.023) while no significant difference was present when the uptakes in other cerebral regions were compared. CONCLUSIONS: The decline of (18F)-FDG uptake in the olfactory bulb occurs earlier than other incidents, serving as an earlier in vivo biological marker of AD in 5XFAD mice and making early diagnosis of AD possibly. PMID- 26265618 TI - Shikonin Promotes Skin Cell Proliferation and Inhibits Nuclear Factor-kappaB Translocation via Proteasome Inhibition In Vitro. AB - BACKGROUND: Shikonin is a major active chemical component extracted from Lithospermi Radix, an effective traditional herb in various types of wound healing. Shikonin can accelerate granulomatous tissue formation by the rat cotton pellet method and induce neovascularization in granulomatous tissue. The purpose of the study was to investigate its mechanism of action in human skin cells. METHODS: MTS assay was used to measure cell growth. The collagen type I (COL1 ) mRNA expression and procollagen type I C-peptide (PIP) production were detected by real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Immunofluorescence and western blot analyses were carried out to investigate nuclear factor-kappaB (NF-kappaB) signaling pathway. Cell-based proteasome activity assay was used to determine proteasome activity. RESULTS: In this study, we found that 10 MUmol/L shikonin stimulated the growth of normal human keratinocytes and 1 MUmol/L shikonin promoted growth of human dermal fibroblasts. However, shikonin did not directly induce COL1 mRNA expression and PIP production in dermal fibroblasts in vitro. In addition, 1 MUmol/L shikonin inhibited translocation of NF-kappaB p65 from cytoplasm to nucleus induced by tumor necrosis factor-alpha stimulation in dermal fibroblasts. Furthermore, shikonin inhibited chymotrypsin-like activity of proteasome and was associated with accumulation of phosphorylated inhibitor kappaB-alpha in dermal fibroblasts. CONCLUSIONS: These results suggested that shikonin may promote wound healing via its cell growth promoting activity and suppress skin inflammation via inhibitory activity on proteasome. Thus, shikonin may be a potential therapeutic reagent both in wound healing and inflammatory skin diseases. PMID- 26265619 TI - Prophylactic Antitumor Effect of Mixed Heat Shock Proteins/Peptides in Mouse Sarcoma. AB - BACKGROUND: To develop a vaccine-based immunotherapy for sarcoma, we evaluated a mixture of heat shock proteins (mHSPs) as a vaccine for sarcoma treatment in a mouse model. Heat shock protein/peptides (HSP/Ps) are autoimmune factors that can induce both adaptive and innate immune responses; HSP/Ps isolated from tumors can induce antitumor immune activity when used as vaccines. METHODS: In this study, we evaluated the effects of mHSP/Ps on prophylactic antitumor immunity. We extracted mHSP/Ps, including HSP60, HSP70, GP96, and HSP110, from the mouse sarcoma cell lines S180 and MCA207 using chromatography. The immunity induced by mHSP/Ps was assessed using flow cytometry, ELISPOT, lactate dehydrogenase release, and enzyme-linked immunosorbent assay. RESULTS: Of S180 sarcoma-bearing mice immunized with mHSP/Ps isolated from S180 cells, 41.2% showed tumor regression and long-term survival, with a tumor growth inhibition rate of 82.3% at 30 days. Of MCA207 sarcoma-bearing mice immunized with mHSP/Ps isolated from MCA207 cells, 50% showed tumor regression and long-term survival with a tumor growth inhibition rate of 79.3%. All control mice died within 40 days. The proportions of natural killer cells, CD8+, and interferon-gamma-secreting cells and tumor-specific cytotoxic T-lymphocyte activity were increased in the immunized group. CONCLUSIONS: Vaccination with a polyvalent mHSP/P cancer vaccine can induce an immunological response and a marked antitumor response to autologous tumors. This mHSP/P vaccine exerted greater antitumor effects than did HSP70, HSP60, or tumor lysates alone. PMID- 26265620 TI - Epithelial Sodium and Chloride Channels and Asthma. AB - OBJECTIVE: To focus on the asthmatic pathogenesis and clinical manifestations related to epithelial sodium channel (ENaC)/chlorine ion channel. DATA SOURCES: The data analyzed in this review were the English articles from 1980 to 2015 from journal databases, primarily PubMed and Google Scholar. The terms used in the literature search were: (1) ENaCs; cystic fibrosis (CF) transmembrane conductance regulator (CFTR); asthma/asthmatic, (2) ENaC/sodium salt; CF; asthma/asthmatic, (3) CFTR/chlorine ion channels; asthma/asthmatic, (4) ENaC/sodium channel/scnn1a/scnn1b/scnn1g/scnn1d/amiloride-sensitive/amiloride-inhibtable sodium channels/sodium salt; asthma/asthmatic, lung/pulmonary/respiratory/tracheal/alveolar, and (5) CFTR; CF; asthma/asthmatic (ti). STUDY SELECTION: These studies included randomized controlled trials or studies covering asthma pathogenesis and clinical manifestations related to ENaC/chlorine ion channels within the last 25 years (from 1990 to 2015). The data involving chronic obstructive pulmonary disease and CF obtained from individual studies were also reviewed by the authors. RESULTS: Airway surface liquid dehydration can cause airway inflammation and obstruction. ENaC and CFTR are closely related to the airway mucociliary clearance. Ion transporters may play a critical role in pathogenesis of asthmatic exacerbations. CONCLUSIONS: Ion channels have been the center of many studies aiming to understand asthmatic pathophysiological mechanisms or to identify therapeutic targets for better control of the disease. PMID- 26265621 TI - Commensal Microbiome Promotes Resistance to Local and Systemic Infections. AB - OBJECTIVE: In this review, to illustrate the resistance mechanism for pathogen insult, we discussed the role of the intestinal microbiome in promoting resistance to local gastrointestinal tract infections and to respiratory tract infections. DATA SOURCES: The review was based on data obtained from the published research articles. STUDY SELECTION: A total of 49 original articles were selected in accordance with our main objective to illustrate the resistance mechanism(s) by which commensal microbiota can contribute to host defense against local and systemic infections. RESULTS: Diverse microorganisms colonize human environmentally exposed surfaces such as skin, respiratory tract, and gastrointestinal tract. Co-evolution has resulted in these microbes with extensive and diverse impacts on multiple aspects of host biological functions. During the last decade, high-throughput sequencing technology developed has been applied to study commensal microbiota and their impact on host biological functions. By using pathogen recognition receptors pathway and nucleotide binding oligomerization domain-like receptors pathway, the commensal microbiome promotes resistance to local and systemic infections, respectively. To protect against the local infections, the microbiome functions contain the following: the competing for sites of colonization, direct production of inhibition molecules or depletion of nutrients needed for pathogens, and priming immune defenses against pathogen insult. At the same time, with the purpose to maintain homeostasis, the commensal bacteria can program systemic signals toward not only local tissue but also distal tissue to modify their function for infections accordingly. CONCLUSIONS: Commensal bacteria play an essential role in protecting against infections, shaping and regulating immune responses, and maintaining host immune homeostasis. PMID- 26265622 TI - Nipple-sparing Mastectomy in Breast Cancer: From an Oncologic Safety Perspective. AB - OBJECTIVE: To evaluate the oncologic safety of nipple-sparing mastectomy (NSM) for breast cancer patients based on current literature. DATA SOURCES: A comprehensive literature search of Medline, Embase databases was conducted for studies published through March 2014. STUDY SELECTION: Our search criteria included English-language studies that focused on NSM at nipple-areola complex (NAC) involvement, patient selection, and recurrence. Prophylaxis NSM, case series or reports that based on very small population were excluded. In the end, 42 studies concerning NSM and oncological safety were included into the review. RESULTS: NSM is a surgical procedure that allows the preservation of the skin and NAC in breast cancer patients or in patients with prophylactic mastectomy. However, the oncologic safety and patient selection criteria associated with NSM are still under debate. The incidence of NAC involvement of breast cancer in recent studies ranges from 9.5% to 24.6%, which can be decreased through careful patient selection. Tumour-nipple distance, tumour size, lymph node involvement and molecular characteristics can be evaluated preoperatively by clinical examinations, imaging studies and biopsies to predict the risk of NAC involvement. Currently, there is no available standard protocol for surgical approaches to NSM or pathological examination of NSM specimens. The local recurrence (ranges from 0% to 24%) of NSM is not significantly higher than that of traditional mastectomy in selected patients based on long-term follow-up. The role of radiotherapy in NSM is still controversial and is not universally accepted. CONCLUSIONS: NSM appears to be oncologically safe following careful patient selection and assessment of margins. PMID- 26265623 TI - Laparoscopic Partial Nephrectomy by Diode Laser with Highly Selective Clamping of Segmental Renal Arterial. PMID- 26265624 TI - Diagnosis and Management of 60 Children with Congenital Vascular Rings: A 10-year Experience: Corrigendum. PMID- 26265625 TI - Integrated Therapy for Invasive Pulmonary Aspergillosis in a Patient with Asthma and Chronic Obstructive Pulmonary Disease Overlap Syndrome. PMID- 26265626 TI - Successful Ablation of Cavo-tricuspid Isthmus Dependent Atrial Flutter in a Patient with Senning Operation. PMID- 26265627 TI - Identification of a Novel Four and a Half LIM Domain 1 Mutation in a Chinese Male Presented with Hypertrophic Cardiomyopathy and Mild Skeletal Muscle Hypertrophy. PMID- 26265628 TI - Paraneoplastic Eosinophilia in Clear Cell Renal Cell Carcinoma. PMID- 26265630 TI - A Rapid, High-Quality, Cost-Effective, Comprehensive and Expandable Targeted Next Generation Sequencing Assay for Inherited Heart Diseases. AB - RATIONALE: Thousands of mutations across >50 genes have been implicated in inherited cardiomyopathies. However, options for sequencing this rapidly evolving gene set are limited because many sequencing services and off-the-shelf kits suffer from slow turnaround, inefficient capture of genomic DNA, and high cost. Furthermore, customization of these assays to cover emerging targets that suit individual needs is often expensive and time consuming. OBJECTIVE: We sought to develop a custom high throughput, clinical-grade next-generation sequencing assay for detecting cardiac disease gene mutations with improved accuracy, flexibility, turnaround, and cost. METHODS AND RESULTS: We used double-stranded probes (complementary long padlock probes), an inexpensive and customizable capture technology, to efficiently capture and amplify the entire coding region and flanking intronic and regulatory sequences of 88 genes and 40 microRNAs associated with inherited cardiomyopathies, congenital heart disease, and cardiac development. Multiplexing 11 samples per sequencing run resulted in a mean base pair coverage of 420, of which 97% had >20* coverage and >99% were concordant with known heterozygous single nucleotide polymorphisms. The assay correctly detected germline variants in 24 individuals and revealed several polymorphic regions in miR-499. Total run time was 3 days at an approximate cost of $100 per sample. CONCLUSIONS: Accurate, high-throughput detection of mutations across numerous cardiac genes is achievable with complementary long padlock probe technology. Moreover, this format allows facile insertion of additional probes as more cardiomyopathy and congenital heart disease genes are discovered, giving researchers a powerful new tool for DNA mutation detection and discovery. PMID- 26265631 TI - Risk factors identified for owner-reported feline obesity at around one year of age: Dry diet and indoor lifestyle. AB - Obesity is considered the second most common health problem in pet cats in developed countries. Previous studies investigating risk factors for feline obesity have been cross-sectional, where reverse causality cannot be ruled out. This study is the first to use prospective data from a large scale longitudinal study of pet cats ('Bristol Cats') to identify early-life risk factors for feline overweight/obesity at around one year of age. Data analysed were collected via three owner-completed questionnaires (for cats aged 2-4 months, 6.5-7 months and 12.5-13 months) completed between May 2010 and August 2013. Owner-reported body condition scores (BCS) of cats at age 12.5-13 months, using the 5-point system, were categorised into a dichotomous variable: overweight/obese (BCS 4-5) and not overweight (BCS 1-3) and used as the dependent variable. Cat breed, neuter status, outdoor access, type of diet, frequency of wet and dry food fed and frequency of treats fed were analysed as potential risk factors. Of the 966 cats for which data were available, 7.0% were reported by their owners to be overweight/obese at 12.5-13 months of age. Descriptive data on type of diet fed at different cat ages suggest that a dry diet is the most popular choice for UK domestic cats. Significant potential explanatory variables from univariable logistic regression models were included in multivariable logistic regression models built using stepwise forward-selection. To account for potential hierarchical clustering of data due to multi-cat households these were extended to two-level random intercept models. Models were compared using Wald test p- values. Clustering had no impact on the analysis. The final multivariable logistic regression model identified two risk factors that were independently associated with an increased risk of feline obesity developing at 12.5-13 months of age: restricted or no outdoor access and feeding dry food as the only or major (>50%) type of food in the diet at age 12.5-13 months. The same relationship was revealed when only variables containing prospective data were included in the multivariable model. The study highlights the importance of a cat's early environment in the risk of obesity developing in early adulthood. The amount of food fed, opportunities for exercise and BCS of cats with no or restricted outdoor access and cats fed a dry diet should be monitored, especially whilst cats are aged below one year, to reduce the risk of overweight/obesity developing. PMID- 26265629 TI - Serine Protease Activation Essential for Endothelial-Mesenchymal Transition in Vascular Calcification. AB - RATIONALE: Endothelial cells have the ability to undergo endothelial-mesenchymal transitions (EndMTs), by which they acquire a mesenchymal phenotype and stem cell like characteristics. We previously found that EndMTs occurred in the endothelium deficient in matrix gamma-carboxyglutamic acid protein enabling endothelial cells to contribute cells to vascular calcification. However, the mechanism responsible for initiating EndMTs is not fully understood. OBJECTIVE: To determine the role of specific serine proteases and sex determining region Y-box 2 (Sox2) in the initiation of EndMTs. METHODS AND RESULTS: In this study, we used in vivo and in vitro models of vascular calcification to demonstrate that serine proteases and Sox2 are essential for the initiation of EndMTs in matrix gamma-carboxyglutamic acid protein-deficient endothelium. We showed that expression of a group of specific serine proteases was highly induced in endothelial cells at sites of vascular calcification in Mgp null aortas. Treatment with serine protease inhibitors decreased both stem cell marker expression and vascular calcification. In human aortic endothelial cells, this group of serine proteases also induced EndMTs, and the activation of proteases was mediated by Sox2. Knockdown of the serine proteases or Sox2 diminished EndMTs and calcification. Endothelial specific deletion of Sox2 decreased expression of stem cell markers and aortic calcification in matrix gamma-carboxyglutamic acid protein-deficient mice. CONCLUSIONS: Our results suggest that Sox2-mediated activation of specific serine proteases is essential for initiating EndMTs, and thus, may provide new therapeutic targets for treating vascular calcification. PMID- 26265632 TI - Court rules that FDA cannot restrict off-label marketing. PMID- 26265633 TI - Burning bright or burning out? PMID- 26265634 TI - Choroidal thickness profile in healthy Indian children. AB - PURPOSE: The purpose was to study choroidal thickness and its profile based on location in healthy Indian children using enhanced depth spectral-domain-optical coherence tomography (SD-OCT). METHODS: In this cross-sectional observational study 255 eyes of 136 children with no retinal or choroidal disease were consecutively scanned using enhanced depth SD-OCT. Eyes with any ocular disease or axial length (AXL) >25 mm or < 20 mm were excluded. A single observer measured choroidal thickness from the posterior edge of the retinal pigment epithelium to the choroid/sclera junction at 500-microns intervals up to 2500 microns temporal and nasal to the fovea. Generalized estimating equations were used to evaluate the correlation between choroidal thickness at various locations and age, AXL, gender and spherical equivalent (SEq). RESULTS: Mean age of the subjects was 11.9 +/- 3.4 years (range: 5-18 years). There were 62 Females and 74 males. The mean AXL was 23.55 +/- 0.74 mm. Mean subfoveal choroidal thickness was 312.1 +/- 45.40 MUm. Choroid was found to be thickest subfoveally, then temporally. Age, AXL and SEq showed a significant correlation with choroidal thickness, whereas gender did not affect choroidal thickness. CONCLUSION: Our study provides a valid normative database of choroidal thickness in healthy Indian children. This database could be useful for further studies evaluating choroidal changes in various chorioretinal disorders. Age and AXL are critical factors, which negatively correlated with choroidal thickness. PMID- 26265636 TI - Personal and practice profile of male and female ophthalmologists in India. AB - BACKGROUND: The aim of this study was to study the practice pattern, personal profile, and work-family balance of male and female ophthalmologists in India. MATERIALS AND METHODS: This study was conducted through 41 point questionnaire sent to the members of All India Ophthalmological Society dealing with practice profile and personal circumstances of ophthalmologists. RESULTS: Six hundred and twenty-two (8%) responses were obtained out of 7723 invitations sent. A total of 452 were male and 170 were female ophthalmologists. Age group of 30-39 years was most common age of respondents (male 155; 35.3%; female 81; 47.6%). Larger number of male ophthalmologists (157; 34.7%) worked for more than 9 h a day than female ophthalmologists (41; 24.1%) (P = 0.01). Larger number of male ophthalmologists (229; 50.7%) earned more than Rs. 1 lakh/month than female ophthalmologists (55; 32.4%) (P = 0.00001) More female ophthalmologists (21; 12.4%) than males (26; 5.8%) said that they faced cultural, ethnic or gender bias at work place (P = 0.002). Forty-four (25.9%) female and 54 (12%) male ophthalmologists said that they often curtailed their work for family needs (P = 0.0001). Two hundred and fifty-two (55.8%) male ophthalmologists and 78 (45.9%) female ophthalmologists considered their profession rewarding (P = 0.02). CONCLUSION: Ophthalmology as a profession was considered rewarding by both male and female ophthalmologists. However, female ophthalmologists were curtailing their work for family needs and earning less than male ophthalmologists. Female ophthalmologists were also subject to gender bias at workplace. These issues need to be tackled to improve the work satisfaction of ophthalmology workforce. PMID- 26265635 TI - Foveal slope measurements in diabetic retinopathy: Can it predict development of sight-threatening retinopathy? Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SN-DREAMS II, Report no 8). AB - AIM: The aim was to assess the foveal slope configuration in subjects with type 2 diabetes in a population-based study. MATERIALS AND METHODS: A subset of 668 subjects from Sankara Nethralaya Diabetic Retinopathy (DR) Epidemiology and Molecular Genetics Study II, a population-based study, were included in the current study. All the subjects underwent comprehensive ophthalmic evaluation including spectral domain optical coherence tomography. Foveal thickness was assessed in five central early treatment DR study quadrants from the three dimensional scan and foveal slope was calculated in all the four quadrants. RESULTS: Subjects with sight-threatening DR (STDR) had significantly shallow foveal slope in inferior quadrant (STDR: 7.33 +/- 6.26 vs. CONTROLS: 10.31 +/- 3.44; P = 0.021) when compared to controls and in superior (STDR: 7.62 +/- 5.81 vs. no DR: 9.11 +/- 2.82; P = 0.033), inferior (STDR: 7.33 +/- 6.26 vs. no DR: 8.81 +/- 2.81; P = 0.048), and temporal quadrants (STDR: 6.69 +/- 5.70 vs. no DR: 7.97 +/- 2.33; P = 0.030) when compared to subjects with no DR. Foveal slope was significantly shallow among the older age groups in subjects with no DR (P < 0.001) and non-STDR (P = 0.027). Average foveal slope in the diabetic subjects was independently and significantly correlated with increase in age (r = -0.241; P < 0.001) and central subfield thickness (r = -0.542; P < 0.001). CONCLUSION: Changes in foveal slope were seen with increasing age; however, in diabetes these segmental slope changes can be seen in late DR (STDR). PMID- 26265637 TI - Effect of biaxial versus coaxial microincision cataract surgery on optical quality of the cornea. AB - CONTEXT: Visual function is determined by a combination of the cornea, which has a larger effect and internal aberrations generated by the intraocular lens and those induced by the surgery. These corneal refractive changes are related to the location and size of the corneal incision. The smaller the incision, the lower the aberrations and the better the optical quality. AIMS: To compare the effect of uneventful coaxial versus biaxial microincision cataract surgery (MICS) on the corneal aberrations. SETTINGS AND DESIGN: Retrospective interventional nonrandomized comparative case study comprised 40 eyes of 36 patients with primary senile cataract. SUBJECTS AND METHODS: They were divided into two groups: Group I (20 eyes) had operated by biaxial MICS and Group II (20 eyes) had operated by coaxial MICS. Each group were assessed by corneal topography and wavefront analysis over 6 mm pupil size preoperatively and 1-month postoperatively. STATISTICAL ANALYSIS USED: Statistical analysis was performed using SPSS for Windows (version 17.0.1, SPSS, Inc.). The paired t-test was used to compare the mean values of corneal aberrations preoperatively and 1-month postoperatively in each group. RESULTS: There was a significant increase in trefoil and quatrefoil in biaxial MICS (P = 0.063, 0.032 respectively) while other aberrations insignificantly changed. The coaxial MICS showed a significant increase in root mean square (RMS) of total high order aberrations (HOAs) (P = 0.02) and coma (0.028), but not the others. In comparison to each other, there was the insignificant difference as regards astigmatism, RMS of individual and total HOAs. CONCLUSIONS: Coaxial and biaxial MICS are neutral on corneal astigmatism and aberrations. PMID- 26265638 TI - Outcome of different techniques of pterygium excision with conjunctival autografting in pediatric population: Our experience in central India. AB - AIM: To analyze surgical outcome of pterygium excision with conjunctival autografting in pediatric population <=16 years. SETTINGS AND DESIGN: Retrospective case series. MATERIALS AND METHODS: A case sheet review of 145 patients (167 eyes) aged <=16 years consecutively presented with pterygium from April 2008 to August 2014 in the single center was done. Twenty-six eyes of 25 children who underwent pterygium excision with conjunctival autograft were analyzed. Different techniques used to secure conjunctival autograft in a position were multiple interrupted 8-0 vicryl sutures, single 8-0 vicryl suture in the center of graft and sutureless glue free. Outcome measures were a failure of surgery and recurrence. RESULTS: Of the total 167 eyes, 26 eyes of 25 children, mean age 13.07 +/- 3.08 years (range 7-16 years) were managed surgically with pterygium excision and conjunctival autograft. The rest of the patients were managed conservatively. In 18 eyes, the graft was secured with multiple sutures, in 6 eyes with a single suture, whereas in 2 eyes, sutureless glue-free graft opposition was done. Mean follow-up was 8.03 months. No case of graft retraction, graft dehiscence or graft displacement was found. Recurrence occurred in 6 eyes and managed surgically. CONCLUSIONS: Occurrence of pterygium is not uncommon in the pediatric population. A single suture or sutureless glue free technique may be good alternative for securing conjunctival autograft after pterygium excision in children. PMID- 26265639 TI - Cost-effectiveness analysis should continually assess competing health care options especially in high volume environments like cataract surgery. AB - CONTEXT: Cost-effectiveness analysis should continually assess competing health care options especially in high volume environments like cataract surgery. AIMS: To compare the cost effectiveness of phacoemulsification (PE) versus manual small incision cataract surgery (MSICS). SETTINGS AND DESIGN: Prospective randomized controlled trial. Tertiary care hospital setting. SUBJECTS AND METHODS: A total of 52 consenting patients with age-related cataracts, were prospectively recruited, and block randomized to PE or MSICS group. Preoperative and postoperative LogMAR visual acuity (VA), visual function-14 (VF-14) score and their quality-adjusted life years (QALYs) were obtained, and the change in their values calculated. These were divided by the total cost incurred in the surgery to calculate and compare the cost effectiveness and cost utility. Surgery duration was also compared. STATISTICAL ANALYSIS USED: Two group comparison with Student's t-test. Significance set at P < 0.05; 95% confidence interval (CI) quoted where appropriate. RESULTS: Both the MSICS and PE groups achieved comparative outcomes in terms of change (difference in mean [95% CI]) in LogMAR VA (0.03 [-0.05-0.11]), VF-14 score (7.92 [-1.03-16.86]) and QALYs (1.14 [-0.89 3.16]). However, with significantly lower costs (INR 3228 [2700-3756]), MSICS was more cost effective, with superior cost utility value. MSICS was also significantly quicker (10.58 min [6.85-14.30]) than PE. CONCLUSIONS: MSICS provides comparable visual and QALY improvement, yet takes less time, and is significantly more cost-effective, compared with PE. Greater push and penetration of MSICS, by the government, is justifiably warranted in our country. PMID- 26265640 TI - Evaluating the change in central corneal thickness in neonates (term and preterm) in Indian population and the factors affecting it. AB - BACKGROUND AND AIM: Central corneal thickness (CCT) of term and preterm infants in Indian population is not known. We did a prospective noninterventional study to measure the CCT in term and preterm infants. MATERIALS AND METHODS: An ultrasonic pachymeter was used. The data regarding the date of birth, expected date of delivery, birth weight were recorded. The preterm and the term infants were followed up at 8 weeks, 20 weeks and at 1-year. RESULTS: A total of 85 (170 eyes) children were included in the study. The mean age was 264.6 +/- 21.8 days postconception. The mean birth weight and CCT were 1834.4 +/- 512.1 g and 595.8 +/- 72.4 MU respectively. A comparison of CCT on the basis postgestational age showed a mean thickness of 620.7 +/- 88.8 and 574.4 +/- 78.3 MU in the <260 days and >260 days age groups respectively. The difference was statistically significant (Student's test, P = 0.002). The CCT of preterm infants (<260 days) decreased from a mean value of 620.7 +/- 88.8 MU to 534.1 +/- 57.6 MU at the end of 1-year. CONCLUSION: We present the data of CCT in term and preterm infants in Indian population. We believe that the premature babies have slightly thicker corneas than mature term babies. PMID- 26265641 TI - Pars plana vitrectomy versus three intravitreal injections of bevacizumab for nontractional diabetic macular edema. A prospective, randomized comparative study. AB - BACKGROUND: The aim of this study was to compare the effectiveness of pars plana vitrectomy (PPV) and removal of the internal limiting membrane (ILM) with three, monthly, intravitreal bevacizumab (IVB) injections for refractory diabetic macular edema. MATERIALS AND METHODS: This was a prospective, randomized, comparative, interventional study. Forty-four patients were enrolled and randomized in two groups. Twenty-two eyes enrolled in Group I received three IVB injections at monthly interval. Twenty-two eyes were enrolled in Group II which underwent PPV with ILM removal. The primary outcomes measured were: (1) Best corrected logMAR visual acuity (BCVA) using Snellen's visual acuity chart. (2) Central macular thickness (CMT) on optical coherence tomography. The secondary outcome measures were: Complication rates like (1) progression of lens opacities, (2) high intraocular pressure needing further treatment/procedure, (3) development of vitreous hemorrhage related to the procedure employed, (4) retinal detachment and (5) severe inflammation/endophthalmitis. RESULTS: In Group I (IVB): 3 (13.6%) eyes showed no change in BCVA; 3 (13.6%) eyes reported decrease in BCVA and 16 (72.8%) eyes showed improvement in BCVA; (P = 0.0181). In Group II (PPV): 4 (18.2%) eyes showed no change in BCVA; 5 (22.7%) eyes showed decrease and 13 (59.1%) eyes showed improvement in BCVA (P = 0.0281). Mean decrease in CMT in IVB group was 108.45 MU, whereas mean decrease in CMT in PPV group was 161.36 MU. No major complications were seen in either group. CONCLUSION: Posttreatment decrease in CMT was more in PPV group and vision improvement more in IVB group. However, no statistically significant difference between the two methods was found. PMID- 26265642 TI - Impact of initial topical medical therapy on short-term quality of life in newly diagnosed patients with primary glaucoma. AB - PURPOSE: To evaluate the impact of initial topical medical therapy on newly diagnosed glaucoma patients using the Indian Vision Function Questionnaire (IND VFQ33). PATIENTS AND METHODS: The IND-VFQ33 was used to evaluate the quality of life (QoL) in 62 newly diagnosed patients with moderate to severe primary glaucoma and 60 healthy controls. IND-VFQ33 is a 33 item QoL assessment tool with three domains: General functioning, psychosocial impact and visual symptoms. The glaucoma patients were started on medical therapy and the QoL assessment was repeated after 3 months. RESULTS: Glaucoma patients (mean age: 55.6 +/- 9.6 years, range 40-77 years) and controls (mean age: 54.9 +/- 6.7 years, 42-73 years) were matched with respect to age (P = 0.72), gender (P = 0.91) and literacy (P = 0.18). Glaucoma patients had significantly worse QoL as compared to controls at baseline across all the three domains (P < 0.001). 3 months after initiation of treatment, the overall QoL life significantly worsened from baseline with a decrease in general functioning (P < 0.001) and psychosocial impact (P = 0.041). Visual acuity in better eye significantly co-related to poor QoL at baseline (P < 0.001) and at 3 months (P = 0.04). In addition, the use of >2 topical medications significantly co-related to poor QoL at 3 months (P = 0.01). CONCLUSIONS: Evaluation using the IND-VFQ33 revealed that newly diagnosed glaucoma patients have a significant worsening of QoL after initiation of topical ocular hypotensive therapy. This should be an important consideration when educating patients about the disease and its therapy. PMID- 26265643 TI - Cost-effectiveness of anti-oxidant vitamins plus zinc treatment to prevent the progression of intermediate age-related macular degeneration. A Singapore perspective. AB - PURPOSE: To determine if providing high dose anti-oxidant vitamins and zinc treatment age-related eye disease study (AREDS formulation) to patients with intermediate age-related macular degeneration (AMD) aged 40-79 years from Singapore is cost-effective in preventing progression to wet AMD. METHODS: A hypothetical cohort of category 3 and 4 AMD patients from Singapore was followed for 5 calendar years to determine the number of patients who would progress to wet AMD given the following treatment scenarios: (a) AREDS formulation or placebo followed by ranibizumab (as needed) for wet AMD. (b) AREDS formulation or placebo followed by bevacizumab (monthly) for wet AMD. (c) AREDS formulation or placebo followed by aflibercept (VIEW I and II trial treatment regimen). Costs were estimated for the above scenarios from the providers' perspective, and cost effectiveness was measured by cost per disability-adjusted life year (DALY) averted with a disability weight of 0.22 for wet AMD. The costs were discounted at an annual rate of 3%. RESULTS: Over 5400 patients could be prevented from progressing to wet AMD cumulatively if AREDS formulation were prescribed. AREDS formulation followed by ranibizumab was cost-effective compared to placebo ranibizumab or placebo-aflibercept combinations (cost per DALY averted: SGD$23,662.3 and SGD$21,138.8, respectively). However, bevacizumab (monthly injections) alone was more cost-effective compared to AREDS formulation followed by bevacizumab. CONCLUSION: Prophylactic treatment with AREDS formulation for intermediate AMD patients followed by ranibizumab or for patients who progressed to wet AMD was found to be cost-effective. These findings have implications for intermediate AMD screening, treatment and healthcare planning in Singapore. PMID- 26265644 TI - Sinonasal carcinoma presenting as chronic sinusitis and sequential bilateral visual loss. AB - Sinonasal undifferentiated carcinoma-related rhinogenic optic neuropathy is rare and may lead to visual loss. To the best of our knowledge, this is the first report of bilateral sequential visual loss induced by this etiology. It is important to differentiate between chronic sinusitis and malignancy on the basis of specific findings on magnetic resonance images. Surgical decompression with multidisciplinary therapy, including steroids, chemotherapy, and radiotherapy, is indicated. However, no visual improvement was noted in this case, emphasizing the rapid disease progression and importance of early diagnosis and treatment. PMID- 26265645 TI - Giant nevus of Ota. PMID- 26265646 TI - Microperimetry biofeedback training in a patient with bilateral myopic macular degeneration with central scotoma. AB - Microperimetry-1 (MP-1) evaluation and MP-1 biofeedback training were done in a case of bilateral myopic macular degeneration with a central scotoma. Fixation behavior, location and stability of preferred retinal locus, eye movement speed, and mean sensitivity were assessed. The mean retinal sensitivities before, after and at 1-year after training in the right eye were 2.9 dB, 2.9 dB and 3.7 dB and in the left eye were 3.5 dB, 3.7 dB and 1.8 dB. The fixation point in the 2 degrees gravitation circle, improved from 40% to 50% in the right eye and from 43% to 67% in the left eye. The average eye speed before, after and at 1-year after training in right eye were 0.19 degrees /s, 0.26 degrees /s and 0.25 degrees /s and in left eye were 0.36 degrees /s, 0.25 degrees /s and 0.27 degrees /s. Thus, biofeedback training using MP-1 can improve the visual function in patients with macular diseases and central scotoma. PMID- 26265647 TI - Traumatic central serous chorioretinopathy. AB - Central serous chorioretinopathy (CSR) is well described in the literature, with recognized associations such as systemic steroid therapy and stress; the association of blunt trauma with CSR is highly unusual. A 44-year-old male developed CSR rapidly after blunt trauma to his left eye with a significant reduction in visual acuity to hand movements. Serial optical coherence tomography and fundus fluorescein angiography images are presented. The patient was managed conservatively and spontaneous resolution occurred by 2 months with an excellent visual outcome. There was no evidence of an alternative underlying pathology for the presentation and particularly no signs of posterior uveitis. Investigations for an underlying vascular, inflammatory or infectious cause were all negative. The patient had previously had CSR in his other eye, and this may indicate a potential predisposition to developing the condition, triggered by blunt trauma. PMID- 26265648 TI - Mirtazapine-induced acute angle closure. AB - Acute angle closure (AAC) is an ocular emergency with symptoms including blurred vision, eye pain, headache, nausea, vomiting and reddening of the eye those results from increased intraocular pressure. This clinical condition can lead to permanent damage in vision, thus causing blindness by generating progressive and irreversible optic neuropathy if left untreated. There are several reasons of AAC, including several types of local and systemic medications; mainly sympathomimetics, cholinergics, anti-cholinergics, mydriatics, anti-histamines, antiepileptics like topiramate, tricyclic and tetracyclic antidepressants, serotonin reuptake inhibitors, antipsychotics, sulfa-based drugs and anticoagulants. Mirtazapine, a noradrenergic and specific serotonergic antidepressant, is an atypical antidepressant with a complex pharmacological profile. This case report describes a patient with major depressive disorder, who experienced AAC after the first dosage of mirtazapine treatment, and highlights the importance of close monitoring of individuals under antidepressant treatment particularly immediately after initiation of the drug. PMID- 26265649 TI - Bilateral periorbital and cervicofacial emphysema following retinal surgery and fluid gas exchange in a case of inadvertent globe perforation. AB - Surgical emphysema is defined as gas or air trapped in the subcutaneous tissue plane. Here, we report a rare case of bilateral periorbital and cervicofacial subcutaneous emphysema following a vitreoretinal surgery for inadvertent globe perforation during the administration of peribulbar anesthesia. This condition, although self-resolving when restricted to the subcutaneous plane has the potential to spread into deeper tissue planes such as the retropharyngeal space. The presence of crepitus helps to distinguish it from angioneurotic edema. Ophthalmologists must be sensitive to the fact that surgical emphysema can be a very rare, but possible complication of an intraocular surgery following globe perforation. PMID- 26265650 TI - Anterior segment ischemia following Hummelsheim procedure in a case of sixth nerve palsy. AB - A, 46-year-old Indian male, known hypertensive presented with left esotropia of 25 prism diopters (PD) after head injury in a roadside accident 9 months back. The deviation was constant in nature and was associated with complaints of diplopia in left lateral gaze. Traumatic sixth nerve palsy was diagnosed. The patient underwent left medial rectus recession of 5 mm and a split-tendon transposition of the left superior and inferior recti to the lateral rectus insertion (Hummelsheim procedure). On the first postoperative day, the patient developed corneal edema and anterior chamber reaction of flare 2+ and cells 2+. The pupil was semi-dilated and was sluggishly reacting to light. Anterior segment ischemia was diagnosed, which was managed with topical and systemic steroids. PMID- 26265651 TI - An innovative impression technique for fabrication of a custom made ocular prosthesis. AB - Various impression and fitting techniques have been described in the past for restoring ocular defects. The present article describes a new direct impression technique for recording and rehabilitating ocular defects, by custom-made ocular prosthesis. All the techniques described in the history, mainly concentrated in recording the tissue surface of the defect, which made it difficult to contour the palpebral surface resulting in the poor esthetics of the prosthesis. The present impression technique uses heavy bodied polyvinyl siloxane impression material, which facilitates accurate recording of the tissue surface and the palpebral surface of the defect, resulting in the fabrication of functionally and esthetically acceptable prosthesis. PMID- 26265652 TI - Anesthetic dilemma in planning bilateral cataract surgery for an infant associated with congenital cardiac anomaly. AB - In a patient with tetralogy of Fallot (TOF) and pulmonary atresia, treating the cardiac problem or the associated congenital illness is always a challenge. We describe the challenges and successful initial management of bilateral cataract to prevent visual loss in an infant with TOF with pulmonary atresia. PMID- 26265653 TI - A case of syringocystadenoma papilliferum of eyelid with literature review. AB - Syringocystadenoma papilliferum can rarely affect eyelid skin. The lesion is frequently misdiagnosed as basal cell carcinoma or cyst or squamous cell carcinoma. We are presenting a case that was clinically diagnosed as basal cell carcinoma of eyelid but was later histologically diagnosed as syringocystadenoma papilliferum. PMID- 26265654 TI - Orbital Chondroma: A rare mesenchymal tumor of orbit. AB - While relatively common in the skeletal system, cartilaginous tumors are rarely seen originating from the orbit. Here, we report a rare case of an orbital chondroma. A 27-year-old male patient presented with a painless hard mass in the superonasal quadrant (SNQ) of left orbit since 3 months. On examination, best corrected visual acuity of both eyes was 20/20, with normal anterior and posterior segment with full movements of eyeballs and normal intraocular pressure. Computerized tomography scan revealed well defined soft tissue density lesion in SNQ of left orbit. Patient was operated for anteromedial orbitotomy under general anesthesia. Mass was excised intact and sent for histopathological examination (HPE). HPE report showed lobular aggregates of benign cartilaginous cells with mild atypia suggesting of benign cartilaginous tumor - chondroma. Very few cases of orbital chondroma have been reported in literature so far. PMID- 26265655 TI - Exudative retinal detachment following strabismus surgery in Sturge-Weber syndrome. AB - A 15-year-old boy with Sturge-Weber syndrome underwent strabismus surgery (oculus sinister [OS]) for the treatment of exotropia. The patient's visual acuity (OS) decreased to hand motion 10 days after the surgery. One month after the surgery, the patient's visual acuity decreased to light perception, and a fundus examination showed total exudative retinal detachment (OS). PMID- 26265656 TI - Unicentric Castleman's disease in the orbit: A case report. AB - A 53-year-old man presented with a palpable mass on the left lower eyelid and occasional diplopia. Under suspicion of orbital lymphoma, an excisional biopsy was performed, and histopathology revealed Castleman's disease. Castleman's disease is a rare disorder of the lymphoid system, and only a few cases of Castleman's disease in the orbit have been reported. PMID- 26265657 TI - Heavy eye syndrome: Role of recessions, resections, loop myopexy, and transplants. PMID- 26265658 TI - The muscle transplantation and loop myopexy in so-called heavy eye syndrome. PMID- 26265659 TI - Anti-Inflammatory Treatment With Colchicine in Acute Myocardial Infarction: A Pilot Study. AB - BACKGROUND: Inflammatory processes have been identified as key mediators of the deleterious effects of ischemia/reperfusion in ST-segment-elevation myocardial infarction. Colchicine is a substance with potent anti-inflammatory properties, suitable for safe use in patients with cardiovascular disease. The purpose of this study was to test the hypothesis that a short course of colchicine treatment could lead to reduced infarct size. METHODS AND RESULTS: Patients presenting with ST-segment-elevation myocardial infarction <=12 hours from pain onset (treated with primary percutaneous coronary intervention) were randomly assigned to colchicine or placebo for 5 days. The primary outcome parameter was the area under the curve of creatine kinase-myocardial brain fraction concentration. A subset of patients underwent cardiac MRI with late gadolinium enhancement 6 to 9 days after the index ST-segment-elevation myocardial infarction. One hundred fifty-one patients were included (60 in the MRI substudy). The area under the creatine kinase-myocardial brain fraction curve was 3144 (interquartile range [IQR], 1754-6940) ng.h(-1).mL(-1) in the colchicine group in comparison with 6184 (IQR, 4456-6980) ng.h(-1).mL(-1) in controls (P<0.001). Indexed MRI-late gadolinium enhancement-defined infarct size was 18.3 (IQR, 7.6-29.9) mL/1.73 m(2) in the colchicine group versus 23.2 (18.5-33.4) mL/1.73 m(2) in controls (P=0.019). The relative infarct size (as a proportion to left ventricular myocardial volume) was 13.0 (IQR, 8.0-25.3) % and 19.8 (IQR, 13.7-29.8) %, respectively (P=0.034). CONCLUSIONS: These results suggest a potential benefit of colchicine in ST-segment-elevation myocardial infarction, but further clinical trials are necessary to draw secure conclusions, especially considering the fact that the present study was not powered to assess clinical end points. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01936285. PMID- 26265660 TI - A questionnaire-based survey on 3D image-guided brachytherapy for cervical cancer in Japan: advances and obstacles. AB - The purpose of this study is to survey the current patterns of practice, and barriers to implementation, of 3D image-guided brachytherapy (3D-IGBT) for cervical cancer in Japan. A 30-item questionnaire was sent to 171 Japanese facilities where high-dose-rate brachytherapy devices were available in 2012. In total, 135 responses were returned for analysis. Fifty-one facilities had acquired some sort of 3D imaging modality with applicator insertion, and computed tomography (CT) and magnetic resonance imaging (MRI) were used in 51 and 3 of the facilities, respectively. For actual treatment planning, X-ray films, CT and MRI were used in 113, 20 and 2 facilities, respectively. Among 43 facilities where X ray films and CT or MRI were acquired with an applicator, 29 still used X-ray films for actual treatment planning, mainly because of limited time and/or staffing. In a follow-up survey 2.5 years later, respondents included 38 facilities that originally used X-ray films alone but had indicated plans to adopt 3D-IGBT. Of these, 21 had indeed adopted CT imaging with applicator insertion. In conclusion, 3D-IGBT (mainly CT) was implemented in 22 facilities (16%) and will be installed in 72 (53%) facilities in the future. Limited time and staffing were major impediments. PMID- 26265661 TI - Evaluation of equivalent dose from neutrons and activation products from a 15-MV X-ray LINAC. AB - A high-energy photon beam that is more than 10 MV can produce neutron contamination. Neutrons are generated by the [gamma,n] reactions with a high-Z target material. The equivalent neutron dose and gamma dose from activation products have been estimated in a LINAC equipped with a 15-MV photon beam. A Monte Carlo simulation code was employed for neutron and photon dosimetry due to mixed beam. The neutron dose was also experimentally measured using the Optically Stimulated Luminescence (OSL) under various conditions to compare with the simulation. The activation products were measured by gamma spectrometer system. The average neutron energy was calculated to be 0.25 MeV. The equivalent neutron dose at the isocenter obtained from OSL measurement and MC calculation was 5.39 and 3.44 mSv/Gy, respectively. A gamma dose rate of 4.14 uSv/h was observed as a result of activations by neutron inside the treatment machine. The gamma spectrum analysis showed (28)Al, (24)Na, (54)Mn and (60)Co. The results confirm that neutrons and gamma rays are generated, and gamma rays remain inside the treatment room after the termination of X-ray irradiation. The source of neutrons is the product of the [gamma,n] reactions in the machine head, whereas gamma rays are produced from the [n,gamma] reactions (i.e. neutron activation) with materials inside the treatment room. The most activated nuclide is (28)Al, which has a half life of 2.245 min. In practice, it is recommended that staff should wait for a few minutes (several (28)Al half-lives) before entering the treatment room after the treatment finishes to minimize the dose received. PMID- 26265662 TI - Urgent Call for Research on Middle East Respiratory Syndrome (MERS) in Korea. PMID- 26265663 TI - The Economic Burden of Cancers Attributable to Metabolic Syndrome in Korea. AB - OBJECTIVES: Metabolic syndrome is an important etiologic factor in the development of certain types of cancers. The economic cost of the treatment of cancer has been steadily increasing. We therefore estimated the economic burden of cancers attributable to metabolic syndrome in Korea. METHODS: We reviewed metabolic syndrome-related cancers and relative risk and then calculated population attributable fractions. We analyzed insurance claims data for metabolic syndrome-related cancers in 2012 in order to estimate the direct costs associated with these cancers, including hospitalization, outpatient visits, transportation costs, and caregivers' costs as well as indirect costs such as loss of productivity due to cancer treatment and premature death. RESULTS: In 2012, 18,070 patients in Korea had cancers attributable to metabolic syndrome. The economic burden was USD 199.8 million and the direct and indirect costs were USD 124.5 million and USD 75.3 million, respectively. CONCLUSIONS: We estimated the economic burden of cancers attributable to metabolic syndrome in Korea and the efforts are necessary to reduce this burden. PMID- 26265664 TI - Associations Between the Continuity of Ambulatory Care of Adult Diabetes Patients in Korea and the Incidence of Macrovascular Complications. AB - OBJECTIVES: The goal of this study was to identify association between the continuity of ambulatory care of diabetes patients in South Korea (hereafter Korea) and the incidence of macrovascular complications of diabetes, using claims data compiled by the National Health Insurance Services of Korea. METHODS: This study was conducted retrospectively. The subjects of the study were 43 002 patients diagnosed with diabetes in 2007, who were over 30 years of age, and had insurance claim data from 2008. The macrovascular complications of diabetes mellitus were limited to ischemic heart disease and ischemic stroke. We compared the characteristics of the patients in whom macrovascular complications occurred from 2009 to 2012 to the characteristics of the patients who had no such complications. Multiple logistic regression was used to assess the effects of continuity of ambulatory care on diabetic macrovascular complications. The continuity of ambulatory diabetes care was estimated by metrics such as the medication possession ratio, the quarterly continuity of care and the number of clinics that were visited. RESULTS: Patients with macrovascular complications showed statistically significant differences regarding sex, age, comorbidities, hypertension, dyslipidemia and continuity of ambulatory diabetes care. Visiting a lower number of clinics reduced the odds ratio for macrovascular complications of diabetes. A medication possession ratio below 80% was associated with an increased odds ratio for macrovascular complications, but this result was of borderline statistical significance. CONCLUSIONS: Diabetes care by regular health care providers was found to be associated with a lower occurrence of diabetic macrovascular complications. This result has policy implications for the Korean health care system, in which the delivery system does not work properly. PMID- 26265665 TI - Dental Care Utilization for Examination and Regional Deprivation. AB - OBJECTIVES: Receiving proper dental care plays a significant role in maintaining good oral health. We investigated the relationship between regional deprivation and dental care utilization. METHODS: Multilevel logistic regression was used to identify the relationship between the regional deprivation level and dental care utilization purpose, adjusting for individual-level variables, in adults aged 19+ in the 2008 Korean Community Health Survey (n=220 258). RESULTS: Among Korean adults, 12.8% used dental care to undergo examination and 21.0% visited a dentist for other reasons. In the final model, regional deprivation level was associated with significant variations in dental care utilization for examination (p<0.001). However, this relationship was not shown with dental care utilization for other reasons in the final model. CONCLUSIONS: This study's findings suggest that policy interventions should be considered to reduce regional variations in rates of dental care utilization for examination. PMID- 26265666 TI - Correlations Between the Incidence of National Notifiable Infectious Diseases and Public Open Data, Including Meteorological Factors and Medical Facility Resources. AB - OBJECTIVES: This study was performed to investigate the relationship between the incidence of national notifiable infectious diseases (NNIDs) and meteorological factors, air pollution levels, and hospital resources in Korea. METHODS: We collected and stored 660,000 pieces of publicly available data associated with infectious diseases from public data portals and the Diseases Web Statistics System of Korea. We analyzed correlations between the monthly incidence of these diseases and monthly average temperatures and monthly average relative humidity, as well as vaccination rates, number of hospitals, and number of hospital beds by district in Seoul. RESULTS: Of the 34 NNIDs, malaria showed the most significant correlation with temperature (r=0.949, p<0.01) and concentration of nitrogen dioxide (r=-0.884, p<0.01). We also found a strong correlation between the incidence of NNIDs and the number of hospital beds in 25 districts in Seoul (r=0.606, p<0.01). In particular, Geumcheon-gu was found to have the lowest incidence rate of NNIDs and the highest number of hospital beds per patient. CONCLUSIONS: In this study, we conducted a correlational analysis of public data from Korean government portals that can be used as parameters to forecast the spread of outbreaks. PMID- 26265667 TI - Effects of Smoking on Menopausal Age: Results From the Korea National Health and Nutrition Examination Survey, 2007 to 2012. AB - OBJECTIVES: Decreased fertility and impaired health owing to early menopause are significant health issues. Smoking is a modifiable health-related behavior that influences menopausal age. We investigated the effects of smoking-associated characteristics on menopausal age in Korean women. METHODS: This study used data from the Korea National Health and Nutrition Examination Survey from 2007 to 2012. Menopausal age in relation to smoking was analyzed as a Kaplan-Meier survival curve for 11 510 women (aged 30 to 65 years). The risk of entering menopause and experiencing early menopause (before age 48) related to smoking were assessed using a Cox proportional hazards model. RESULTS: The menopausal age among smokers was 0.75 years lower than that among non-smokers (p<0.001). The results of the Cox proportional hazards model showed pre-correction and post correction risk ratios for entering menopause related to smoking of 1.26 (95% confidence interval [CI], 1.09 to 1.46) and 1.27 (95% CI, 1.10 to 1.47), respectively, and pre-correction and post-correction risk ratios for experiencing early menopause related to smoking of 1.36 (95% CI, 1.03 to 1.80) and 1.40 (95% CI, 1.05 to 1.85), respectively. CONCLUSIONS: Smokers reached menopause earlier than non-smokers, and their risk for experiencing early menopause was higher. PMID- 26265668 TI - The effect of occupational farming on lung function development in young adults: a 15-year follow-up study. AB - OBJECTIVES: Longitudinal studies on the effect of farming on lung function in young participants are few. Our objective was to explore if exposure to farming impaired lung function in young adults. METHODS: We studied 1964 farming students and 407 controls in 1992/2004, and carried out follow-up in 2007/2008. Spirometry, skin prick test and bronchial hyper-responsiveness (BHR) were assessed, height and weight measured, and questionnaires covering health and occupation were collected. Cumulative dust and endotoxin exposures were estimated from modelled personal dust measurements. Lung function effect was expressed as change in z-score during follow-up using the Global Lung Initiative 2012 project prediction equations. Longitudinal data were available for 1134 young participants <=25 years at baseline. RESULTS: We found no differences in lung function Deltaz-scores between farmers and controls, however, adjusted multivariable linear regression showed a negative effect among current farmers on DeltazFEV1 (forced expiratory volume in 1 s; -0.12, p=0.006) and DeltazFEV1/FVC (forced vital capacity; -0.15, p=0.009) compared to ex-farmers. An interaction was found between sex and farming, showing that current farming suppresses DeltazFEV1 and DeltazFVC more among females. Smoking in farmers had a deleterious effect on DeltazFEV1, which was not seen in controls, though no significant interaction was found. Farm upbringing protected against impairment of lung function, and BHR at baseline had a deleterious effect on DeltazFEV1 only in those not raised on a farm. CONCLUSIONS: We conclude that being a current farmer is associated with a negative effect on lung function, when compared to ex farmers, with females being more susceptible. Being raised on a farm protects against the adverse effect of BHR on change in lung function. PMID- 26265669 TI - Pleural mesothelioma and occupational and non-occupational asbestos exposure: a case-control study with quantitative risk assessment. AB - OBJECTIVES: Casale Monferrato (north west Italy) is an area with an exceptionally high incidence of mesothelioma caused by asbestos contamination at work and in the general environment from the asbestos-cement Eternit plant that was operational until 1986. The purpose of this study was to quantify the association between pleural malignant mesothelioma (PMM) and asbestos cumulative exposure using individual assessment of environmental and domestic exposure, as well as of occupational exposure. METHODS: This population-based case-control study included cases of PMM diagnosed between January 2001 and June 2006 among residents in the Casale Monferrato Local Health Authority. Population controls were randomly sampled, matched by age and sex to cases. Cumulative exposure was estimated to account for the lifelong exposure history. Analyses were conducted using unconditional logistic regression models adjusting for gender, age at diagnosis and type of interview (direct or proxy respondents). RESULTS: 200 PMM cases of 223 eligible cases (89.7%) and 348 (63%) of 552 eligible controls accepted to be interviewed. ORs increased with cumulative exposure index (p<0.0001) from 4.4 (CI 95% 1.7 to 11.3) (<1 f/mL-years) to 62.1 (CI 95% 22.2 to 173.2) (>=10 f/mL years). Among subjects never occupationally exposed, corresponding ORs were 3.8 (CI 95% 1.3 to 11.1) and 23.3 (CI 95% 2.9 to 186.9) (reference: background level of asbestos exposure). ORs of about 2, statistically significant, were observed for domestic exposure and for living in houses near buildings with large asbestos cement parts. CONCLUSIONS: Risk of PMM increased with cumulative asbestos exposure and also in analyses limited to subjects non-occupationally exposed. Our results also provide indication of risk associated with common sources of environmental exposure and are highly relevant for the evaluation of residual risk after the cessation of asbestos industrial use. PMID- 26265670 TI - Diminished pulmonary function in long-term workers exposed to cotton dust determined in a cross-sectional study in small Pakistani enterprises. AB - PURPOSE: While large cotton industry plants producing for the foreign market have undergone improvements of occupational hygiene lately, working conditions in power looms producing mainly for the local market are still poor. The respiratory health in workers of power looms has not been studied so far. METHODS: In a cross sectional study, 51 male cotton workers from power looms, 58 from large cotton factories and 52 controls were investigated by spirometry and a symptoms questionnaire. Spirometric measurements and respiratory symptoms were related to exposure duration in large and small factories by multivariate linear regression and logistic regression, respectively, with smoking, age and anthropometric parameters considered as confounders. RESULTS: Work duration in power looms was associated with declines in forced expiratory volume in 1 s, peak flow, maximum midexpiratory flow and forced expiratory flow 75 and an increased risk of obstruction (OR 1.09/year; 95% CI: 1.002 to 1.18) by applying the Global Lung Initiative equations. Except cough that was only associated with smoking, all respiratory symptoms (chest tightness, shortness of breath, fever) increased as a function of duration of exposure in power looms but not in large factories. CONCLUSIONS: Despite limitations inherent in the cross-sectional approach, there is evidence for workers in small weaving factories to face an increased risk of pulmonary function loss and respiratory symptoms. Industrial hygiene measures in these small enterprises should be encouraged. Failure to detect adverse respiratory outcomes from occupation in large factories could be due to a 'survivor' (healthy worker) effect. PMID- 26265671 TI - The mental health of deployed UK maritime forces. AB - OBJECTIVES: To establish the level of psychological symptoms and the risk factors for possible decreased mental health among deployed UK maritime forces. METHODS: A survey was completed by deployed Royal Navy (RN) personnel which measured the prevalence of common mental disorder (CMD), post-traumatic stress disorder (PTSD) and potential alcohol misuse. Military and operational characteristics were also measured including exposure to potentially traumatic events, problems occurring at home during the deployment, unit cohesion, leadership and morale. Associations between variables of interest were identified using binary logistic regression to generate ORs and 95% CIs adjusted for a range of potential confounding variables. RESULTS: In total, 41.2% (n=572/1387) of respondents reported probable CMD, 7.8% (n=109/1389) probable PTSD and 17.4% (n=242/1387) potentially harmful alcohol use. Lower morale, cohesion, leadership and problems at home were associated with CMD; lower morale, leadership, problems at home and exposure to potentially traumatic events were associated with probable PTSD; working in ships with a smaller crew size was associated with potentially harmful alcohol use. CONCLUSIONS: CMD and PTSD were more frequently reported in the maritime environment than during recent land-based deployments. Rates of potentially harmful alcohol use have reduced but remain higher than the wider military. Experiencing problems at home and exposure to potentially traumatic events were associated with experiencing poorer mental health; higher morale, cohesion and better leadership with fewer psychological symptoms. PMID- 26265672 TI - A collaborative strategy to improve geriatric medical education. AB - INTRODUCTION: Age-related demographic change is not being matched by a growth in relevant undergraduate medical education, in particular communication skills pertinent to elderly patients. To address this, a workshop for medical students focusing on important communication skills techniques for interacting with patients with dementia was designed by clinicians from the Geriatric, General Practice and Psychiatry departments at the University of Oxford. METHODS: One hundred and forty-four first-year clinical students (Year 4 of the 6-year course; Year 2 of the 4-year graduate-entry course) attended the teaching. One hundred and twenty-nine students returned feedback forms with 104 forms matched for individual performance before and after the session. Feedback forms assessed student-perceived confidence in communicating with patients with dementia before and after the session using a 4-point Likert scale with corresponding numerical value (low (1), medium (2), high (3), very high (4)). RESULTS: Using the Wilcoxon Signed-Rank Test on the 104 matched forms, student-perceived confidence was higher post-teaching intervention (median = 2.75) than pre-intervention (median = 1.50). This difference was statistically significant with large effect size, Z = 8.47, P < 0.001, r = -0.59. Free-text comments focused on non-verbal communication skills teaching, suggesting that these sessions were most beneficial for topics hardest to teach in lecture-based approaches. CONCLUSION: The teaching aimed to promote patient-centred care and multidisciplinary collaborative practice, encourage student self-reflection and peer-assisted education and provide insight into the needs of patients with dementia. Student feedback indicated that these objectives had been met. This easily replicable teaching method provides a simple means of improving communication skills. PMID- 26265673 TI - Emergency care for frail older people-urgent AND important-but what works? PMID- 26265674 TI - Discharging older patients from the emergency department effectively: a systematic review and meta-analysis. AB - BACKGROUND: a decline in health state and re-attendance are common in people aged >=65 years following emergency department (ED) discharge. Diverse care models have been implemented to support safe community transition. This review examined ED community transition strategies (ED-CTS) and evaluated their effectiveness. METHODS: a systematic review and meta-analysis using multiple databases up to December 2013 was conducted. We assessed eligibility, methodological quality, risk of bias and extracted published data and then conducted random effects meta analyses. Outcomes were unplanned ED representation or hospitalisation, functional decline, nursing-care home admission and mortality. RESULTS: five experimental and four observational studies were identified for qualitative synthesis. ED-CTS included geriatric assessment with referral for post-discharge community-based assistance, with differences apparent in components and delivery methods. Four studies were included in meta-analysis. Compared with usual care, the evidence indicates no appreciable benefit for ED-CTS for unplanned ED re attendance up to 30 days (odds ratio (OR) 1.32, 95% confidence interval (CI) 0.99 1.76; n = 1,389), unplanned hospital admission up to 30 days (OR 0.90, 95% CI 0.70-1.16; n = 1,389) or mortality up to 18 months (OR 1.04, 95% CI 0.83-1.29; n = 1,794). Variability between studies precluded analysis of the impact of ED-CTS on functional decline and nursing-care home admission. CONCLUSIONS: there is limited high-quality data to guide confident recommendations about optimal ED community transition strategies, highlighting a need to encourage better integration of researchers and clinicians in the design and evaluation process, and increased reporting, including appropriate robust evaluation of efficacy and effectiveness of these innovative models of care. PMID- 26265675 TI - Determinants of 25-hydroxyvitamin D in older Irish adults. AB - BACKGROUND: vitamin D deficiency is prevalent in older adults living in Northern Europe and is influenced by several factors which may vary significantly with age. OBJECTIVE: we aimed to investigate the determinants of 25-hydroxyvitamin D [25(OH)D] in older Irish adults and in particular to examine the effect of supplement use and surrogate markers of sun exposure. METHODS: subjects were non institutionalised community dwelling Irish adults aged over 60 years who were participants of a large cross-sectional study comprising three disease defined cohorts. Serum 25(OH)D was measured by liquid chromatography mass spectroscopy. Associations between 25(OH)D and potential confounders were explored in forward regression models in each cohort. RESULTS: the three cohorts comprised 1895, 1233 and 1316 participants (respective mean ages 70.1, 71.0 and 80.4 years). Statistical models explained between a fifth to a third of the variation in 25(OH)D. Supplement use and global solar radiation were positive predictors of 25(OH)D in all cohorts whereas the only universal negative predictor was body mass index. Supplement use was associated with a mean increase in 25(OH)D of between 21.4 and 35.4 nmol/l. The other main predictors varied by cohort but included sun holiday travel, enjoyment of sunshine when outside, use of vitamin D fortified milk, smoking, oily fish and egg consumption and physical frailty. CONCLUSION: supplement use was the most important determinant of vitamin D status. Vitamin D fortified milk and spending time in the sun, even in the oldest old may also be useful strategies to improve 25(OH)D. PMID- 26265676 TI - Horizontal beam technique to document position of percutaneously inserted central venous catheters. PMID- 26265677 TI - Intrauterine inflammation, cerebral oxygen consumption and susceptibility to early brain injury in very preterm newborns. AB - BACKGROUND: In utero exposure to inflammation results in elevated cerebral oxygen consumption. This increased metabolic demand may contribute to the association between chorioamnionitis and intraventricular haemorrhage (P/IVH). We hypothesised that intrauterine inflammation imposes an elevated cerebral metabolic load and increased fractional oxygen extraction (cFTOE) with cFTOE further increased in the presence of early P/IVH. METHODS: Eighty-three infants <=30 weeks gestation were recruited. Exposure to intrauterine inflammation was determined by placental histology. Total internal carotid blood flow (Doppler ultrasound) and near infrared spectroscopy were measured and cerebral oxygen delivery (mcerbDO2), consumption (mcerbVO2) and cFTOE were calculated on days 1 and 3 of life. Primary outcome was defined as death or P/IVH >grade II (cranial sonograph) by day 3. RESULTS: Infants exposed to intrauterine inflammation had higher total internal carotid blood flow (92 vs 63 mL/kg/min) and mcerbDO2 (13.7 vs 10.1 mL/kg/min) than those not exposed to inflammation. Newborns with P/IVH had both higher oxygen consumption and extraction compared with those without sonographic injury regardless of exposure to intrauterine inflammation. Further, in preterms exposed to inflammation, those with P/IVH had higher consumption (6.1 vs 4.8 mL/kg/min) and extraction than those without injury. These differences were observed only on day 1 of life. CONCLUSIONS: Although P/IVH is multifactorial in preterm newborns, it is likely that cerebral hypoxic-ischaemia plays a central pathophysiological role. These data provide a mechanistic insight into this process and suggests that the increased cerebral metabolic load imposed by the presence of inflammation results in a higher risk of critical hypoxic ischaemia in the preterm with increased susceptibility to significant P/IVH. PMID- 26265678 TI - Estimating umbilical catheter insertion depth in newborns using weight or body measurement: a randomised trial. AB - OBJECTIVE: Incorrectly positioned umbilical venous and arterial catheters (UVC and UAC) are associated with increased rates of complications in newborns. Catheter insertion depth is often estimated using body surface measurement. We wished to determine whether estimating insertion depth of umbilical catheters using birth weight (BW), rather than surface measurements, results in more correctly positioned catheters. INTERVENTIONS/OUTCOME: Newborns were randomised to have UVC and UAC insertion depth estimated using formulae based on BW or using graphs based on shoulder-umbilicus length. The primary outcome was correct catheter tip position on X-ray determined by one radiologist masked to group assignment. RESULTS: UVC insertion was successful in 97/101 (96%) infants but the catheter was not advanced to the estimated depth in 22. There was no difference in the proportion of correctly positioned UVCs between groups (weight 16/51 (31%) vs measurement 13/46 (28%), p=0.826). The tips of 52 (54%) UVCs were in the portal venous system or too low on X-ray. Attempted UAC insertion was successful in 62/87 (71%) infants. More infants in the weight group had a correctly positioned UAC tip (weight 29/32 (91%) vs measurement 15/30 (50%), p=0.001). CONCLUSIONS: UVCs were often not inserted to the estimated depth, and their tips were in the portal venous system or too low on X-ray. Using BW to estimate insertion depth did not result in more correctly positioned UVCs. UAC insertion attempts were often unsuccessful, but when successful, using BW to estimate insertion depth resulted in more correctly positioned catheters. TRIAL REGISTRATION NUMBER: (ISRCTN17864069). PMID- 26265679 TI - Millennials at work: workplace environments of young adults and associations with weight-related health. AB - BACKGROUND: The purpose of this study was to describe the workplace environments of young adults and examine associations with diet, physical activity (PA) and body mass index (BMI). METHODS: Cross-sectional data were collected (2008-2009) from 1538 employed young adult participants in Project EAT (Eating and Activity among Teens and Young Adults), a diverse population-based sample. Survey measures assessed height, weight, diet, moderate-to-vigorous PA, transportation-related PA and perceptions of the workplace food and PA environments (eg, soda availability, coworker support). Healthful characteristics were summed to reflect overall workplace healthfulness. Modified Poisson regression analyses conducted in 2015 identified associations between workplace food and PA environments and diet, PA and BMI. RESULTS: The healthfulness of workplace environments was suboptimal. Greater exposure to healthful workplace characteristics was related to more young adults engaged in favourable diet and PA behaviours and a lower prevalence obesity. For example, adjusted rates of obesity were 24% and 17% among those reporting low (<=1 characteristic) versus high (>=3 characteristics) exposure to healthful food environments, respectively (p<0.05). Workplace characteristics independently associated with weight-related outcomes included soda availability, proximity to a fast food outlet, living close to work and perceived ease of eating a healthy diet or being active at work. CONCLUSIONS: A more healthful workplace environment overall, including physical attributes and perceived social norms, may contribute to more favourable weight-related behaviours and lower prevalence of obesity among young adults. Employer-initiated and community initiated policies may represent one way to create healthier workplace environments for young adults. PMID- 26265680 TI - Methods to estimate maternal mortality: a global perspective. PMID- 26265681 TI - Speakers corner. To frack or not to frack? Why is that not a global public health question and how should public health practitioners address it? PMID- 26265682 TI - Technique to manage persistent leak from a prepyloric ulcer where a distal gastrectomy is not appropriate. AB - Perforated peptic ulcer disease remains a relatively frequent emergency surgery presentation. Persistent leak is the most common indication for return to theatre. We present a technique to manage patients in whom a more substantial resection is not possible. A 45-year-old woman underwent initial laparoscopic primary closure of a non-malignant perforated gastric ulcer. This subsequently leaked on return to the UK and had a further graham patch formed via a laparotomy. Unfortunately, the patch repair leaked and at reoperation a wedge excision or distal gastrectomy was not possible given the friability of the tissues and instability of the patient, a transgastric drain and perigastric drain were therefore placed. This created a controlled fistula, which was managed eventually as an outpatient. Transgastric drains in the context of the persistent perforated gastric ulcer leak are a safe way to manage the unstable patient with poor tissues where more substantial surgeries such as a distal gastrectomy are not possible. PMID- 26265683 TI - Cytology Specimen Management, Triage and Standardized Reporting of Fine Needle Aspiration Biopsies of the Pancreas. AB - The recent advances in pancreas cytology specimen sampling methods have enabled a specific cytologic diagnosis in most cases. Proper triage and processing of the cytologic specimen is pivotal in making a diagnosis due to the need for ancillary testing in addition to cytological evaluation, which is especially true in the diagnosis of pancreatic cysts. Newly proposed terminology for pancreaticobiliary cytology offers a standardized language for reporting that aims to improve communication among patient caregivers and provide for increased flexibility in patient management. This review focuses on these updates in pancreas cytology for the optimal evaluation of solid and cystic lesions of the pancreas. PMID- 26265684 TI - SALL4 Expression in Hepatocellular Carcinomas Is Associated with EpCAM-Positivity and a Poor Prognosis. AB - BACKGROUND: There is increasing interest in hepatocellular carcinomas (HCC) expressing "stemness"-related markers, as they have been associated with aggressive behavior and poor prognosis. In this study, we investigated the usefulness of Sal-like protein 4 (SALL4), a recently proposed candidate marker of "stemness." METHODS: Immunohistochemical stains were performed for SALL4, K19, and epithelial cellular adhesion molecule (EpCAM) on tissue microarrays constructed from 190 surgically resected HCCs, and the results were correlated with the clinicopathological features and patient survival data. RESULTS: Nuclear SALL4 expression was observed in 39/190 HCCs (20.5%), while K19 and EpCAM were expressed in 30 (15.9%) and 92 (48.7%) HCCs, respectively. The nuclear expression was generally weak, punctate or clumped. SALL4 expression was significantly associated with a poor overall survival compared to SALL4-negative HCCs (p = .014) compared to SALL4-negative HCCs. On multivariate analysis adjusted for tumor size, multiplicity, vascular invasion, and pathological tumor stage, SALL4 remained as a significant independent predictor of decreased overall survival (p= .004). SALL4 expression was positively correlated with EpCAM expression (p = .013) but not with K19 expression. HCCs that expressed both SALL4 and EpCAM were associated with significantly decreased overall survival, compared to those cases which were negative for both of these markers (p = .031). CONCLUSIONS: Although SALL4 expression was not significantly correlated with other clinicopathological parameters suggestive of tumor aggressiveness, SALL4 expression was an independent predictor of poor overall survival in human HCCs, and was also positively correlated with EpCAM expression. PMID- 26265685 TI - Membranous Insulin-like Growth Factor-1 Receptor (IGF1R) Expression Is Predictive of Poor Prognosis in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Lung Adenocarcinoma. AB - BACKGROUND: Insulin-like growth factor-1 receptor (IGF1R) is a membrane receptor type tyrosine kinase that has attracted considerable attention as a potential therapeutic target, although its clinical significance in non-small cell lung cancer (NSCLC) is controversial. This study aimed to clarify the clinical significance of IGF1R expression in human NSCLC. METHODS: IGF1R protein expression was evaluated using immunohistochemistry in 372 patients with NSCLC who underwent curative surgical resection (146 squamous cell carcinomas [SqCCs] and 226 adenocarcinomas [ADCs]). We then analyzed correlations between expression of IGF1R and clinicopathological and molecular features and prognostic significance. RESULTS: Membranous and cytoplasmic IGF1R expression were significantly higher in SqCCs than in ADCs. In patients with SqCC, membranous IGF1R expression was associated with absence of vascular, lymphatic, and perineural invasion; lower stage; and better progression-free survival (PFS) (hazard ratio [HR], 0.586; p = .040). In patients with ADC, IGF1R expression did not have a significant prognostic value; however, in the subgroup of epidermal growth factor receptor (EGFR)-mutant ADC, membranous IGF1R expression was associated with lymphatic and perineural invasion, solid predominant histology, and higher cancer stage and was significantly associated with worse PFS (HR, 2.582; p = .009). CONCLUSIONS: Lung ADC and SqCC showed distinct IGF1R expression profiles that demonstrated prognostic significance. High membranous IGF1R expression was predictive of poor PFS in EGFR-mutant lung ADC, while it was predictive of better PFS in SqCC. These findings will help improve study design for subsequent investigations and select patients for future anti-IGF1R therapy. PMID- 26265686 TI - Mediastinal Glomus Tumor: A Case Report and Literature Review. AB - A glomus tumor in the mediastinum is very uncommon, and only five cases have been reported in the English literature. We recently encountered a 21-year-old woman with an asymptomatic mediastinal mass that measured 5.3 * 4.0 cm. Surgical excision was performed, and the tumor was finally diagnosed as mediastinal glomus tumor with an uncertain malignant potential. After reviewing this case and previous reports, we analyzed the clinicopathologic features associated with progression of such a tumor. PMID- 26265687 TI - Indeterminate Dendritic Cell Tumor: A Case Report of a Rare Langerhans Cell Lineage Disease. PMID- 26265688 TI - Intrahepatic Cholangiocarcinoma with Ductal Plate Malformation-like Feature Associated with Bile Duct Adenoma. PMID- 26265689 TI - Oncocytic Renal Cell Carcinoma with Tubulopapillary Growth Having a Fat Component. AB - We report a rare case of oncocytic renal cell carcinoma (RCC) with tubulopapillary growth in the background of tuberculous end-stage kidney disease. Histology of the renal mass consisted of oncocytic cells forming solid, thin tubules and rare papillae. The tumor had abundant eosinophilic oncocytic cells containing occasional cytoplasmic Mallory body-like hyaline globules and a tiny focus of clear cells with intervening mature fat. Both the oncocytic cells and clear cells were immunoreactive for a-methylacyl-CoA racemase, vimentin, pancytokeratin, and CD10, and negative for transcription factor E3, CD15, human melanoma black 45, and c-kit. Mallory body-like hyaline globules were positive for CAM 5.2 and periodic acid-Schiff with or without diastase. Ultrastructurally, the tumor cells had abundant cytoplasmic mitochondria. The present case is a rare case of oncocytic RCC with tubulopapillary growth pattern. The case is unique in that the tumor was mixed with fat component, which is not common in RCC and thus can lead to misdiagnosis. PMID- 26265690 TI - Double Para-testicular Cellular Angiofibroma and Synchronous Testicular Microlithiasis. PMID- 26265691 TI - Multifocal Polypoid Endometriosis Mimicking Malignancy in a Young Woman with a History of Hormonal Treatment. PMID- 26265692 TI - A rabbit model of antegrade selective cerebral perfusion with cardioplegic arrest. AB - OBJECTIVE: Due to the weak ascending aorta, it is extremely challenging to establish an anterograde selective cerebral perfusion (ASCP) model in rabbits, especially when cardioplegic arrest is required. Herein, the aim of this study was to establish a rabbit ASCP model with cardiac arrest being easily performed and being similar to the clinical scenario. MATERIALS AND METHODS: Twenty-two adult New Zealand white rabbits were selected for ASCP model establishment and another 22 rabbits were utilized for blood donation. The cardiopulmonary bypass (CPB) circuit consisted of a roller pump, a membrane oxygenator, a heat-cooler system and a blood reservoir, which were connected by silicone tubing. The total priming volume of the circuit was 70 ml. Cannulations on the right and left subclavian arteries were used for arterial inflow and cardioplegia perfusion, respectively. Venous drainage was conducted through the right atrial appendage. ASCP was initiated by clamping the innominate artery; the flow rate was maintained 10 ml/kg/minute and sustained for 60 minutes. After 120 minutes of reperfusion, the rabbits were sacrificed. The mean arterial pressure, heart rate, electrocardiogram and urine output were monitored. Arterial blood samples were analyzed at the following time points: after anesthesia, immediately after CPB, after aorta cross-clamping and cardioplegia perfusion, 5 min after the re-opening of the aorta and at CPB termination. RESULTS: ASCP modeling was performed successfully on 18 rabbits and 4 rabbits unsuccessfully. Vital signs and blood gas indictors changed in an acceptable range throughout the experiments. One rabbit had ventricular fibrillation after re-opening of the ascending aorta. Obvious hemodilution occurred after the perfusion of cardioplegia, but the hematocrit improved after CPB termination. CONCLUSION: By using cannulation of the subclavian artery rather than the aorta and with a low priming volume, we established a modified rabbit model of ASCP with cardioplegic arrest. The model has excellent repeatability and operability, which is similar to the clinic process and is suitable for the study of cerebral, cardiac and renal protection. PMID- 26265693 TI - Prognostic and Chemotherapy Predictive Value of Gene-Expression Phenotypes in Primary Lung Adenocarcinoma. AB - PURPOSE: Primary lung adenocarcinoma remains a deadly disease. Gene-expression phenotypes (GEPs) in adenocarcinoma have potential to provide clinically relevant disease stratification for improved prognosis and treatment prediction, given appropriate clinical and methodologic validation. EXPERIMENTAL DESIGN: 2,395 transcriptional adenocarcinoma profiles were assembled from 17 public cohorts and classified by a nearest centroid GEP classifier into three subtypes: terminal respiratory unit (TRU), proximal-proliferative, and proximal-inflammatory, and additionally scored by five transcriptional metagenes representing different biologic processes, including proliferation. Prognostic- and chemotherapy predictive associations of the subtypes were analyzed by univariate and multivariate analysis using overall survival or distant metastasis-free survival as endpoints. RESULTS: Overall, GEPs were associated with patient outcome in both univariate and multivariate analyses, although not in all individual cohorts. The prognostically relevant division was between TRU- and non-TRU-classified cases, with expression of proliferation-associated genes as a key prognostic component. In contrast, GEP classification was not predictive of adjuvant chemotherapy response. GEP classification showed stability to random perturbations of genes or samples and alterations to classification procedures (typically <10% of cases/cohort switching subtype). High classification variability (>20% of cases switching subtype) was observed when removing larger or entire fractions of a single subtype, due to gene-centering shifts not addressable by the classifier. CONCLUSIONS: In a large-scale evaluation, we show that GEPs add prognostic value to standard clinicopathologic variables in lung adenocarcinoma. Subject to classifier refinement and confirmation in prospective cohorts, GEPs have potential to affect the prognostication of adenocarcinoma patients through a molecularly driven disease stratification. PMID- 26265694 TI - Pretreatment microRNA Expression Impacting on Epithelial-to-Mesenchymal Transition Predicts Intrinsic Radiosensitivity in Head and Neck Cancer Cell Lines and Patients. AB - PURPOSE: Predominant causes of head and neck cancer recurrence after radiotherapy are rapid repopulation, hypoxia, fraction of cancer stem cells, and intrinsic radioresistance. Currently, intrinsic radioresistance can only be assessed by ex vivo colony assays. Besides being time-consuming, colony assays do not identify causes of intrinsic resistance. We aimed to identify a biomarker for intrinsic radioresistance to be used before start of treatment and to reveal biologic processes that could be targeted to overcome intrinsic resistance. EXPERIMENTAL DESIGN: We analyzed both microRNA and mRNA expression in a large panel of head and neck squamous cell carcinoma (HNSCC) cell lines. Expression was measured on both irradiated and unirradiated samples. Results were validated using modified cell lines and a series of patients with laryngeal cancer. RESULTS: miRs, mRNAs, and gene sets that correlated with resistance could be identified from expression data of unirradiated cells. The presence of epithelial-to-mesenchymal transition (EMT) and low expression of miRs involved in the inhibition of EMT were important radioresistance determinants. This finding was validated in two independent cell line pairs, in which the induction of EMT reduced radiosensitivity. Moreover, low expression of the most important miR (miR-203) was shown to correlate with local disease recurrence after radiotherapy in a series of patients with laryngeal cancer. CONCLUSIONS: These findings indicate that EMT and low expression of EMT inhibiting miRs, especially miR-203, measured in pretreatment material, causes intrinsic radioresistance of HNSCC, which could enable identification and treatment modification of radioresistant tumors. Clin Cancer Res; 21(24); 5630-8. (c)2015 AACR. PMID- 26265696 TI - U-shaped mortality curve associated with platelet count among older people: a community-based cohort study. PMID- 26265695 TI - Depletion of the chromatin remodeler CHD4 sensitizes AML blasts to genotoxic agents and reduces tumor formation. AB - Chromodomain helicase DNA-binding protein 4 (CHD4) is an ATPase that alters the phasing of nucleosomes on DNA and has recently been implicated in DNA double stranded break (DSB) repair. Here, we show that depletion of CHD4 in acute myeloid leukemia (AML) blasts induces a global relaxation of chromatin that renders cells more susceptible to DSB formation, while concurrently impeding their repair. Furthermore, CHD4 depletion renders AML blasts more sensitive both in vitro and in vivo to genotoxic agents used in clinical therapy: daunorubicin (DNR) and cytarabine (ara-C). Sensitization to DNR and ara-C is mediated in part by activation of the ataxia-telangiectasia mutated pathway, which is preliminarily activated by a Tip60-dependent mechanism in response to chromatin relaxation and further activated by genotoxic agent-induced DSBs. This sensitization preferentially affects AML cells, as CHD4 depletion in normal CD34(+) hematopoietic progenitors does not increase their susceptibility to DNR or ara-C. Unexpectedly, we found that CHD4 is necessary for maintaining the tumor forming behavior of AML cells, as CHD4 depletion severely restricted the ability of AML cells to form xenografts in mice and colonies in soft agar. Taken together, these results provide evidence for CHD4 as a novel therapeutic target whose inhibition has the potential to enhance the effectiveness of genotoxic agents used in AML therapy. PMID- 26265697 TI - GVHD-associated, inflammasome-mediated loss of function in adoptively transferred myeloid-derived suppressor cells. AB - Myeloid-derived suppressor cells (MDSCs) are a naturally occurring immune regulatory population associated with inhibition of ongoing inflammatory responses. In vitro generation of MDSCs from bone marrow has been shown to enhance survival in an acute model of lethal graft-versus-host disease (GVHD). However, donor MDSC infusion only partially ameliorates GVHD lethality. In order to improve the potential therapeutic benefit and ultimately survival outcomes, we set out to investigate the fate of MDSCs after transfer in the setting of acute GVHD (aGVHD). MDSCs transferred to lethally irradiated recipients of allogeneic donor hematopoietic grafts are exposed to an intense inflammatory environment associated with aGVHD, which we now show directly undermines their suppressive capacity. Under a conditioning regimen and GVHD inflammatory settings, MDSCs rapidly lose suppressor function and their potential to inhibit GVHD lethality, which is associated with their induced conversion toward a mature inflammasome activated state. We find even brief in vitro exposure to inflammasome-activating mediators negates the suppressive potential of cultured murine and human-derived MDSCs. Consistent with a role for the inflammasome, donor MDSCs deficient in the adaptor ASC (apoptosis-associated speck-like protein containing a CARD), which assembles inflammasome complexes, conferred improved survival of mice developing GVHD compared with wild-type donor MDSCs. These data suggest the use of MDSCs as a therapeutic approach for preventing GVHD and other systemic inflammatory conditions will be more effective when combined with approaches limiting in vivo MDSC inflammasome activation, empowering MDSCs to maintain their suppressive potential. PMID- 26265698 TI - Hydroxyurea with AKT2 inhibition decreases vaso-occlusive events in sickle cell disease mice. AB - Heterotypic cell-cell adhesion and aggregation mediate vaso-occlusive events in patients with sickle cell disease (SCD). Although hydroxyurea (HU), an inducer of fetal hemoglobin, is the main therapy for treatment of SCD, it is unclear whether it has immediate benefits in acute vaso-occlusive events in SCD patients. Using real-time fluorescence intravital microscopy, we demonstrated that short-term coadministration of HU and Akti XII, an AKT2 inhibitor, efficiently reduced neutrophil adhesion and platelet-neutrophil aggregation in venules of Berkeley (SCD) mice challenged with tumor necrosis factor alpha (TNF-alpha) or hypoxia/reoxygenation. Importantly, compared with HU or Akti XII treatment alone, short-term treatment with both agents significantly improved survival in those mice. We found that the level of plasma nitric oxide species was elevated by HU but not Akti XII, AKT2 phosphorylation levels in activated neutrophils and platelets were reduced by Akti XII but not HU, and the expression of endothelial E-selectin and intercellular adhesion molecule 1 was decreased by either agent. Our results suggest that short-term coadministration of HU and Akti XII has immediate benefits for acute vaso-occlusive events and survival in SCD mice exceeding those seen for single therapy. PMID- 26265700 TI - [Congratulations to including in MEDLINE of Korean Journal of Medical Education]. PMID- 26265699 TI - Genetics of glucocorticoid-associated osteonecrosis in children with acute lymphoblastic leukemia. AB - Glucocorticoids are important therapy for acute lymphoblastic leukemia (ALL) and their major adverse effect is osteonecrosis. Our goal was to identify genetic and nongenetic risk factors for osteonecrosis. We performed a genome-wide association study of single nucleotide polymorphisms (SNPs) in a discovery cohort comprising 2285 children with ALL, treated on the Children's Oncology Group AALL0232 protocol (NCT00075725), adjusting for covariates. The minor allele at SNP rs10989692 (near the glutamate receptor GRIN3A locus) was associated with osteonecrosis (hazard ratio = 2.03; P = 3.59 * 10(-7)). The association was supported by 2 replication cohorts, including 361 children with ALL on St. Jude's Total XV protocol (NCT00137111) and 309 non-ALL patients from Vanderbilt University's BioVU repository treated with glucocorticoids (odds ratio [OR] = 1.87 and 2.26; P = .063 and .0074, respectively). In a meta-analysis, rs10989692 was also highest ranked (P = 2.68 * 10(-8)), and the glutamate pathway was the top ranked pathway (P = 9.8 * 10(-4)). Osteonecrosis-associated glutamate receptor variants were also associated with other vascular phenotypes including cerebral ischemia (OR = 1.64; P = 2.5 * 10(-3)), and arterial embolism and thrombosis (OR = 1.88; P = 4.2 * 10(-3)). In conclusion, osteonecrosis was associated with inherited variations near glutamate receptor genes. Further understanding this association may allow interventions to decrease osteonecrosis. These trials are registered at www.clinicaltrials.gov as #NCT00075725 and #NCT00137111. PMID- 26265702 TI - Efficient Endocytic Uptake and Maturation in Drosophila Oocytes Requires Dynamitin/p50. AB - Dynactin is a multi-subunit complex that functions as a regulator of the Dynein motor. A central component of this complex is Dynamitin/p50 (Dmn). Dmn is required for endosome motility in mammalian cell lines. However, the extent to which Dmn participates in the sorting of cargo via the endosomal system is unknown. In this study, we examined the endocytic role of Dmn using the Drosophila melanogaster oocyte as a model. Yolk proteins are internalized into the oocyte via clathrin-mediated endocytosis, trafficked through the endocytic pathway, and stored in condensed yolk granules. Oocytes that were depleted of Dmn contained fewer yolk granules than controls. In addition, these oocytes accumulated numerous endocytic intermediate structures. Particularly prominent were enlarged endosomes that were relatively devoid of Yolk proteins. Ultrastructural and genetic analyses indicate that the endocytic intermediates are produced downstream of Rab5. Similar phenotypes were observed upon depleting Dynein heavy chain (Dhc) or Lis1. Dhc is the motor subunit of the Dynein complex and Lis1 is a regulator of Dynein activity. We therefore propose that Dmn performs its function in endocytosis via the Dynein motor. Consistent with a role for Dynein in endocytosis, the motor colocalized with the endocytic machinery at the oocyte cortex in an endocytosis-dependent manner. Our results suggest a model whereby endocytic activity recruits Dynein to the oocyte cortex. The motor along with its regulators, Dynactin and Lis1, functions to ensure efficient endocytic uptake and maturation. PMID- 26265703 TI - The Spontaneous Mutation Rate in the Fission Yeast Schizosaccharomyces pombe. AB - The rate at which new mutations arise in the genome is a key factor in the evolution and adaptation of species. Here we describe the rate and spectrum of spontaneous mutations for the fission yeast Schizosaccharomyces pombe, a key model organism with many similarities to higher eukaryotes. We undertook an ~1700 generation mutation accumulation (MA) experiment with a haploid S. pombe, generating 422 single-base substitutions and 119 insertion-deletion mutations (indels) across the 96 replicates. This equates to a base-substitution mutation rate of 2.00 * 10(-10) mutations per site per generation, similar to that reported for the distantly related budding yeast Saccharomyces cerevisiae. However, these two yeast species differ dramatically in their spectrum of base substitutions, the types of indels (S. pombe is more prone to insertions), and the pattern of selection required to counteract a strong AT-biased mutation rate. Overall, our results indicate that GC-biased gene conversion does not play a major role in shaping the nucleotide composition of the S. pombe genome and suggest that the mechanisms of DNA maintenance may have diverged significantly between fission and budding yeasts. Unexpectedly, CpG sites appear to be excessively liable to mutation in both species despite the likely absence of DNA methylation. PMID- 26265704 TI - Obese Nondiabetic Pregnancies and High Maternal Glycated Hemoglobin at Delivery as an Indicator of Offspring and Maternal Postpartum Risks: The Prospective PEACHES Mother-Child Cohort. AB - BACKGROUND: We investigated whether obese pregnant women negative for gestational diabetes (GDM) still experience dysglycemia, as indicated by high glycated hemoglobin (Hb A1c) at delivery, and whether this impacts offspring and long-term maternal outcomes. METHODS: Data of 462 mother-child pairs of our prospective Programming of Enhanced Adiposity Risk in Childhood - Early Screening (PEACHES) cohort study were analyzed. Of 885 obese and normal-weight pregnancies prospectively enrolled after GDM testing according to the International Association of Diabetes and Pregnancy Study Groups criteria, 462 GDM-negative mothers and their offspring were investigated. We assessed associations of maternal Hb A1c at delivery with large-for-gestational-age (LGA) birth weights, cord-blood C-peptide, and biomarkers of glucose metabolism and inflammation in obese mothers followed for 2.9 years (median) postpartum (n = 42). RESULTS: Cumulative distribution analysis in GDM-negative normal-weight women (n = 155) revealed that 12% had Hb A1c >=5.7% at delivery (high Hb A1c). Among obese GDM negative women (n = 307), 31.9% (95% CI, 26.7%-37.4%) equaled or exceeded this cutoff. In obese GDM-negative women with Hb A1c >=5.7% (n = 98) vs <5.7% (n = 209) at delivery, newborns were more likely to be born LGA [adjusted odds ratio 3.56 (95% CI, 1.64-8.02)], and mean cordblood serum C-peptide was increased by 0.09 ng/mL (95% CI, 0.01-0.17 ng/mL). In the mothers at follow-up, mean postpartum Hb A1c, fasting glucose, high-sensitivity C-reactive protein, and fibrinogen concentrations were higher by 0.3% (95% CI, 0.1%-0.5%), 6.0 mg/dL (95% CI, 2.4-9.5 mg/dL), 6.8 mg/L (95% CI, 1.4-12.3 mg/L), and 74.9 mg/dL (95% CI, 13.6-136.2 mg/dL), respectively. CONCLUSIONS: Increased Hb A1c in obese GDM negative women at delivery indicates gestational dysglycemia, potentially conferring offspring and long-term maternal health risks. These findings should raise awareness as to careful monitoring of obese pregnancies. Measurement of Hb A1c at delivery could help select women who may need closer postpartum health checks. PMID- 26265705 TI - More people opt to use assisted dying laws for greater variety of reasons. PMID- 26265707 TI - Simple risk score for colon cancer identifies people likely to benefit from colonoscopy. PMID- 26265706 TI - Synthesis of efficient gene delivery systems by grafting pegylated alkylcarboxylate chains to PAMAM dendrimers: Evaluation of transfection efficiency and cytotoxicity in cancerous and mesenchymal stem cells. AB - The applications of polyamidoamine (PAMAM) dendrimers have attracted much attention in biomedicine specially non-viral gene delivery because of thier unique characteristics including hyperbranching, multivalency, and well-defined uniform globular three-dimensional structures. In the current study, in order to enhance the transfection efficiency and reduce the cytotoxicity of PAMAMs, bromoalkylcarboxylates with different chain length (2-bromoacetic, 6 bromohexanoic, 10-bromodecanoic and 16-bromohexadecanoic acids) were covalently conjugated with 10% and 30% of primary amines of generation 4 and 5 (G4 and G5) of PAMAM dendrimers to increase the hydrophobicity of the carrier. At the next stage, the alkylcarboxylate-PAMAMs were pegylaed to further modify the PAMAM structures for biological applications. Obtained results demonstrated that the prepared PAMAM derivatives had particle size around 140 nm with net-positive surface charge. None of the prepared PAMAM-based non-viral vactors exhibited significant hemolytic activity and also cytotoxicity. Meanwhile decahexanoate PAMAM G4 [G4(16C-10%)] and decanoate-PAMAM G4 conjugated to polyethylene glycol (PEG) (G4[(10C-30%)(10C-PEG)]) showed highest transfection efficiency in murine neuroblastoma (Neuro-2a) cell line, interestingly only the latter had improved transfection efficiency in mesenchymal stem cells (MSCs). This study proved the potential utility of alkylcarboxylate-grafted PAMAM dendrimers (G4 and G5) with or without PEG modification for efficient gene transfer into cancerous cells as well as MSCs. PMID- 26265708 TI - Defining criteria for good environmental journalism and testing their applicability: An environmental news review as a first step to more evidence based environmental science reporting. AB - While the quality of environmental science journalism has been the subject of much debate, a widely accepted benchmark to assess the quality of coverage of environmental topics is missing so far. Therefore, we have developed a set of defined criteria of environmental reporting. This instrument and its applicability are tested in a newly established monitoring project for the assessment of pieces on environmental issues, which refer to scientific sources and therefore can be regarded as a special field of science journalism. The quality is assessed in a kind of journalistic peer review. We describe the systematic development of criteria, which might also be a model procedure for other fields of science reporting. Furthermore, we present results from the monitoring of 50 environmental reports in German media. According to these preliminary data, the lack of context and the deficient elucidation of the evidence pose major problems in environmental reporting. PMID- 26265709 TI - UK science press officers, professional vision and the generation of expectations. AB - Science press officers can play an integral role in helping promote expectations and hype about biomedical research. Using this as a starting point, this article draws on interviews with 10 UK-based science press officers, which explored how they view their role as science reporters and as generators of expectations. Using Goodwin's notion of 'professional vision', we argue that science press officers have a specific professional vision that shapes how they produce biomedical press releases, engage in promotion of biomedical research and make sense of hype. We discuss how these insights can contribute to the sociology of expectations, as well as inform responsible science communication. PMID- 26265710 TI - Representing climate change on public service television: A case study. AB - Publicly funded broadcasters with a track record in science programming would appear ideally placed to represent climate change to the lay public. Free from the constraints of vested interests and the economic imperative, public service providers are better equipped to represent the scientific, social and economic aspects of climate change than commercial media, where ownership conglomeration, corporate lobbyists and online competition have driven increasingly tabloid coverage with an emphasis on controversy. This prime-time snapshot of the Australian Broadcasting Corporation's main television channel explores how the structural/rhetorical conventions of three established public service genres - a science programme, a documentary and a live public affairs talk show - impact on the representation of anthropogenic climate change. The study findings note implications for public trust, and discuss possibilities for innovation in the interests of better public understanding of climate change. PMID- 26265711 TI - Political implications of science popularisation strategies: Frontiers of S cience. AB - This examination of the mediation strategies of a very popular factual science comic strip series from the 1960s and 1970s illustrates, in this case by highlighting the ways in which women were targeted as an audience, that science popularisations are always political. For that reason, they should not be evaluated merely in terms of scientific accuracy. I demonstrate tensions between the dissemination model of communication used in the distribution of science popularisations, on the one hand, with the advocacy of a dialogue model in their content, on the other. PMID- 26265712 TI - Joint statement on redundant (duplicate) publication by the Editors of the undersigned cardio-thoracic journals. PMID- 26265713 TI - Cell-Based High-Throughput Luciferase Reporter Gene Assays for Identifying and Profiling Chemical Modulators of Endoplasmic Reticulum Signaling Protein, IRE1. AB - Endoplasmic reticulum (ER) stress activates three distinct signal transducers on the ER membrane. Inositol-requiring protein 1 (IRE1), the most conserved signal transducer, plays a key role in ER stress-mediated signaling. During ER stress, IRE1 initiates two discrete signaling cascades: the "adaptive" signaling cascade mediated by the XBP1 pathway and the "alarm" signaling cascade mediated by stress activated protein kinase pathways. Fine-tuning of the balance between the adaptive and alarm signals contributes significantly to cellular fate under ER stress. Thus, we propose that the design of high-throughput screening (HTS) assays to selectively monitor IRE1 mediated-signaling would be desirable for drug discovery. To this end, we report the generation of stable human neural cell lines and development of cell-based HTS luciferase (Luc) reporter gene assays for the identification of pathway-specific chemical modulators of IRE1. We implemented a cell-based Luc assay using a chimeric CHOP-Gal4 transcription factor in 384-well format for monitoring IRE1 kinase-mediated p38MAPK activation and an unfolded response pathway element (URPE)-Luc cell-based assay in 1536-well format for monitoring IRE1's RNase-mediated activation of XBP1. Chemical library screening was successfully conducted with both the CHOP/Gal4-Luc cells and UPRE Luc engineered cells. The studies demonstrate the feasibility of using these HTS assays for discovery of pathway-selective modulators of IRE1. PMID- 26265714 TI - A 22 year old woman with bilateral panuveitis and parotid swelling. PMID- 26265715 TI - Chronic Renal Insufficiency Cohort Study (CRIC): Overview and Summary of Selected Findings. AB - The Chronic Renal Insufficiency Cohort (CRIC) Study is a United States multicenter, prospective study of racially and ethnically diverse patients with CKD. Although the original aims of the study were to identify novel predictors of CKD progression and to elucidate the risk and manifestations of cardiovascular disease among nearly 4000 individuals with CKD, the CRIC Study has evolved into a national resource for investigation of a broad spectrum of CKD-related topics. The study has produced >90 published scientific articles, promoted many young investigative careers in nephrology, and fostered international collaborations focused on understanding the global burden of CKD. The third phase of the CRIC Study will complete enrollment of 1500 additional study participants in 2015 and is designed to answer questions regarding morbidity and mortality in mild-to moderate CKD and to assess the burden of CKD in older persons. This review highlights some of the salient findings of the CRIC Study in the areas of race and ethnicity, CKD progression, CKD and cognition, and cardiovascular disease outcomes; it also outlines the ongoing and forthcoming opportunities for the global nephrology community to enhance its understanding of CKD and related complications through the study. PMID- 26265716 TI - The Experiences of Korean Young Adult Survivors of Childhood Cancer: A Photovoice Study. AB - Photovoice was used to understand the impact of childhood cancer on Korean young adult survivors. Seven survivors of childhood cancer (currently aged 20-27 years), diagnosed before the age of 19 and with cancer treatment completed, participated in five sessions. The participants took photographs that captured their group's weekly topics and participated in discussions about their feelings and experiences. Fifty-six photo images with narratives on the survivors' experiences were produced on these four participant-selected themes: Relationships With Others, Stigma, Overcoming Difficulties, and The Future This study on Korean childhood cancer survivors sheds light on their perspectives about the impact of cancer. Using an innovative methodology that takes the participants' point of view, this study contributes to the literature on young adult cancer survivors' quality of life and their psychosocial adjustment. The results can inform educational programs and increase public awareness by providing survivors' schoolteachers and peers with knowledge about childhood cancer. PMID- 26265717 TI - Independent Co-Option of a Tailed Bacteriophage into a Killing Complex in Pseudomonas. AB - Competition between microbes is widespread in nature, especially among those that are closely related. To combat competitors, bacteria have evolved numerous protein-based systems (bacteriocins) that kill strains closely related to the producer. In characterizing the bacteriocin complement and killing spectra for the model strain Pseudomonas syringae B728a, we discovered that its activity was not linked to any predicted bacteriocin but is derived from a prophage. Instead of encoding an active prophage, this region encodes a bacteriophage-derived bacteriocin, termed an R-type syringacin. This R-type syringacin is striking in its convergence with the well-studied R-type pyocin of P. aeruginosa in both genomic location and molecular function. Genomic alignment, amino acid percent sequence identity, and phylogenetic inference all support a scenario where the R type syringacin has been co-opted independently of the R-type pyocin. Moreover, the presence of this region is conserved among several other Pseudomonas species and thus is likely important for intermicrobial interactions throughout this important genus. IMPORTANCE: Evolutionary innovation is often achieved through modification of complexes or processes for alternate purposes, termed co-option. Notable examples include the co-option of a structure functioning in locomotion (bacterial flagellum) to one functioning in protein secretion (type three secretion system). Similar co-options can occur independently in distinct lineages. We discovered a genomic region in the plant pathogen Pseudomonas syringae that consists of a fragment of a bacteriophage genome. The fragment encodes only the tail of the bacteriophage, which is lethal toward strains of this species. This structure is similar to a previously described structure produced by the related species Pseudomonas aeruginosa. The two structures, however, are not derived from the same evolutionary event. Thus, they represent independent bacteriophage co-options. The co-opted bacteriophage from P. syringae is found in the genomes of many other Pseudomonas species, suggesting ecological importance across this genus. PMID- 26265718 TI - Heat-Labile Enterotoxin IIa, a Platform To Deliver Heterologous Proteins into Neurons. AB - Cholera toxin (CT) and the related heat-labile enterotoxins (LT) of Escherichia coli have been implicated as adjuvants in human therapies, but reactivity upon intranasal delivery dampened efforts to develop other clinical applications. However, each CT family member variant has unique biological properties that may warrant development as therapeutic platforms. In the current study, a nontoxic variant of the heat-labile enterotoxin IIa (LTIIa) was engineered to deliver heterologous, functional proteins into the cytosol of neurons. As proof of principle, the LTIIa variant delivered two cargos into neurons. LTIIa delivered beta-lactamase efficiently into cells containing complex gangliosides, such as GD1b, as host receptors. LTIIa delivery of beta-lactamase was sensitive to brefeldin A, an inhibitor that collapses the Golgi compartment into the endoplasmic reticulum, but not sensitive to treatment with botulinum neurotoxin D (BoNT/D), an inhibitor of synaptic vesicle cycling. LTIIa delivered a single chain, anti-BoNT/A camelid antibody that inhibited SNAP25 cleavage during post BoNT/A exposure of neurons. Delivery of functional, heterologous protein cargos into neurons demonstrates the potential of LTII variants as platforms to deliver therapies to inactivate toxins and microbial infections and to reverse the pathology of human neurodegenerative diseases. IMPORTANCE: This study engineered a protein platform to deliver functional, heterologous proteins into neurons. The protein platform developed was a variant of the heat-labile enterotoxin IIa (LTIIa) which lacked the catalytic domain, yielding a nontoxic protein. As proof of principle, LTIIa variants delivered two functional proteins into neurons, beta lactamase and a camelid antibody. These studies show the utility of LTIIa variants to deliver therapies into neurons, which could be extended to inactivate toxins and microbial infections and potentially to reverse the progression of neurological diseases, such as Alzheimer's disease and Parkinson's disease. PMID- 26265720 TI - Statins May Decrease the Fatality Rate of Middle East Respiratory Syndrome Infection. PMID- 26265719 TI - Structural and Functional Adaptation of Vancomycin Resistance VanT Serine Racemases. AB - Vancomycin resistance in Gram-positive bacteria results from the replacement of the D-alanyl-D-alanine target of peptidoglycan precursors with D-alanyl-D-lactate or D-alanyl-D-serine (D-Ala-D-Ser), to which vancomycin has low binding affinity. VanT is one of the proteins required for the production of D-Ala-D-Ser terminating precursors by converting L-Ser to D-Ser. VanT is composed of two domains, an N-terminal membrane-bound domain, likely involved in L-Ser uptake, and a C-terminal cytoplasmic catalytic domain which is related to bacterial alanine racemases. To gain insight into the molecular function of VanT, the crystal structure of the catalytic domain of VanTG from VanG-type resistant Enterococcus faecalis BM4518 was determined. The structure showed significant similarity to type III pyridoxal 5'-phosphate (PLP)-dependent alanine racemases, which are essential for peptidoglycan synthesis. Comparative structural analysis between VanTG and alanine racemases as well as site-directed mutagenesis identified three specific active site positions centered around Asn696 which are responsible for the L-amino acid specificity. This analysis also suggested that VanT racemases evolved from regular alanine racemases by acquiring additional selectivity toward serine while preserving that for alanine. The 4-fold-lower relative catalytic efficiency of VanTG against L-Ser versus L-Ala implied that this enzyme relies on its membrane-bound domain for L-Ser transport to increase the overall rate of d-Ser production. These findings illustrate how vancomycin pressure selected for molecular adaptation of a housekeeping enzyme to a bifunctional enzyme to allow for peptidoglycan remodeling, a strategy increasingly observed in antibiotic-resistant bacteria. IMPORTANCE: Vancomycin is one of the drugs of last resort against Gram-positive antibiotic-resistant pathogens. However, bacteria have evolved a sophisticated mechanism which remodels the drug target, the D-alanine ending precursors in cell wall synthesis, into precursors terminating with D-lactate or D-serine, to which vancomycin has less affinity. D-Ser is synthesized by VanT serine racemase, which has two unusual characteristics: (i) it is one of the few serine racemases identified in bacteria and (ii) it contains a membrane-bound domain involved in L-Ser uptake. The structure of the catalytic domain of VanTG showed high similarity to alanine racemases, and we identified three specific active site substitutions responsible for L-Ser specificity. The data provide the molecular basis for VanT evolution to a bifunctional enzyme coordinating both transport and racemization. Our findings also illustrate the evolution of the essential alanine racemase into a vancomycin resistance enzyme in response to antibiotic pressure. PMID- 26265721 TI - A 1,000-Year-Old Antimicrobial Remedy with Antistaphylococcal Activity. AB - Plant-derived compounds and other natural substances are a rich potential source of compounds that kill or attenuate pathogens that are resistant to current antibiotics. Medieval societies used a range of these natural substances to treat conditions clearly recognizable to the modern eye as microbial infections, and there has been much debate over the likely efficacy of these treatments. Our interdisciplinary team, comprising researchers from both sciences and humanities, identified and reconstructed a potential remedy for Staphylococcus aureus infection from a 10th century Anglo-Saxon leechbook. The remedy repeatedly killed established S. aureus biofilms in an in vitro model of soft tissue infection and killed methicillin-resistant S. aureus (MRSA) in a mouse chronic wound model. While the remedy contained several ingredients that are individually known to have some antibacterial activity, full efficacy required the combined action of several ingredients, highlighting the scholarship of premodern doctors and the potential of ancient texts as a source of new antimicrobial agents. IMPORTANCE: While the antibiotic potential of some materials used in historical medicine has been demonstrated, empirical tests of entire remedies are scarce. This is an important omission, because the efficacy of "ancientbiotics" could rely on the combined activity of their various ingredients. This would lead us to underestimate their efficacy and, by extension, the scholarship of premodern doctors. It could also help us to understand why some natural compounds that show antibacterial promise in the laboratory fail to yield positive results in clinical trials. We have reconstructed a 1,000-year-old remedy which kills the bacteria it was designed to treat and have shown that this activity relies on the combined activity of several antimicrobial ingredients. Our results highlight (i) the scholarship and rational methodology of premodern medical professionals and (ii) the untapped potential of premodern remedies for yielding novel therapeutics at a time when new antibiotics are desperately needed. PMID- 26265722 TI - Dual-Use Research of Concern (DURC) Review at American Society for Microbiology Journals. PMID- 26265723 TI - Suitability of the Zenith p-Branch Standard Fenestrated Endovascular Graft for Treatment of Ruptured Abdominal Aortic Aneurysms. AB - PURPOSE: To evaluate the anatomic suitability of the Zenith pivot branch (p branch) fenestrated device in ruptured abdominal aortic aneurysms (rAAA). METHODS: Contrast-enhanced computed tomography (CT) images of 206 patients (mean age 75+/-8 years; 175 men) with rAAA were evaluated in a dedicated 3-dimensional vascular workstation. All aneurysms found unsuitable for standard infrarenal repair were evaluated for Zenith p-branch suitability according to the Investigational Device Exemption protocol for both device configurations (A, pivot fenestrations at the same level; B, right renal fenestration located more cranially). RESULTS: The suitability of the p-branch (A or B configuration) for short neck aneurysms (<15 mm; n=89) was 49%; of the 26 different combinations of exclusion criteria, a mismatch between a renal artery takeoff and the positioning of the corresponding fenestration was the most common. For juxta- and pararenal aneurysms (neck length <10 mm; n=66), suitability was 48%. Suitability assessed by target vessel positioning only (excluding all other limiting factors) was 58% for short neck aneurysms (n=52) and 55% for juxta- and pararenal aneurysms (n=36). CONCLUSION: Approximately half of patients with short neck rAAAs would be suitable for the Zenith p-branch fenestrated device according to the instructions for use. In almost 60%, the pivot fenestrations can accommodate the corresponding target vessels. More studies are needed to confirm these findings. PMID- 26265725 TI - Putting a price on empathy: against incentivising moral enhancement. AB - Concerns that people would be disinclined to voluntarily undergo moral enhancement have led to suggestions that an incentivised programme should be introduced to encourage participation. This paper argues that, while such measures do not necessarily result in coercion or undue inducement (issues with which one may typically associate the use of incentives in general), the use of incentives for this purpose may present a taboo trade-off. This is due to empirical research suggesting that those characteristics likely to be affected by moral enhancement are often perceived as fundamental to the self; therefore, any attempt to put a price on such traits would likely be deemed morally unacceptable by those who hold this view. A better approach to address the possible lack of participation may be to instead invest in alternative marketing strategies and remove incentives altogether. PMID- 26265724 TI - Hepatic encephalopathy due to liver cirrhosis. PMID- 26265726 TI - Antibiotics without prescription: more cons than pros. PMID- 26265727 TI - A High Omega-3 Fatty Acid Multinutrient Supplement Benefits Cognition and Mobility in Older Women: A Randomized, Double-blind, Placebo-controlled Pilot Study. AB - BACKGROUND: Mobility is a key determinant of frailty in older persons, and a variety of dietary factors, such as the omega-3 fatty acid docosahexaenoic acid (DHA), are positively associated with decreased frailty and improved mobility and cognition in older persons. METHODS: The effects of a multinutrient supplement on mobility and cognition were assessed in postmenopausal women (60-84 years). Participants received either Efalex Active 50+ (1g DHA, 160 mg eicosapentaenoic acid, 240 mg Ginkgo biloba, 60 mg phosphatidylserine, 20mg d-alpha tocopherol, 1mg folic acid, and 20 ug vitamin B12 per day; N = 15) or placebo (N = 12) for 6 months. Mobility was assessed by VICON 9 motion capture camera system synchronized with Kistler force plates, cognitive performance by computerized cognitive function tests, and blood fatty acid levels by pin-prick analysis. RESULTS: Significant effects of treatment were seen in two of the four cognitive tests, with shorter mean latencies in a motor screening task (p < .05) and more words remembered (p < .03), and one of the three primary mobility measures with improved habitual walking speed (p < .05). Compared with the placebo group, supplementation also resulted in significantly higher blood DHA levels (p < .02). CONCLUSIONS: In this pilot study, multinutrient supplementation improved cognition and mobility in able older females at clinically relevant levels, suggesting a potential role in reducing the decline to frailty. PMID- 26265728 TI - Identifying Sarcopenia in Metabolic Syndrome: Data from the Berlin Aging Study II. AB - BACKGROUND: The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors which has been linked with a decline in muscle mass. However, with a variety of sarcopenia definitions, it is unclear which approach is suitable to detect reduced muscle mass in subjects with MetS who are frequently characterized by an increased fat mass and higher body weight. METHODS: We analyzed cross sectional data of 1,402 (51.1% female; 69+/-3.7 years) old community-dwelling subjects of the Berlin Aging Study II. MetS was defined according to the guidelines of the International Diabetes Federation/American Heart Association/National Heart, Lung, and Blood Institute (IDF/AHA/NHLBI, 2009). Sarcopenia was defined as suggested by Baumgartner et al. (low appendicular lean mass corrected for height, ALM/HT(2)) and according to standardized residuals following the approach suggested by Newman et al., which corrects appendicular lean mass (ALM) for weight and height. RESULTS: MetS was identified in 35% of the participants, 25.6% had sarcopenia according to ALM/HT(2), 20% according to the residual approach. We compared the two operational parameters and found that the majority of physical and metabolic parameters were more impaired and self reported difficulties in physical performance were greater in individuals defined sarcopenic according to residuals than subjects who were sarcopenic according to a low ALM/HT(2). CONCLUSION: Our results indicate that an approach to define sarcopenia which corrects ALM both for height and weight is more suitable to detect increased physical limitations as well as higher metabolic impairment, compared to adjustment of ALM only for height. PMID- 26265729 TI - Tequila Regulates Insulin-Like Signaling and Extends Life Span in Drosophila melanogaster. AB - The aging process is a universal phenomenon shared by all living organisms. The identification of longevity genes is important in that the study of these genes is likely to yield significant insights into human senescence. In this study, we have identified Tequila as a novel candidate gene involved in the regulation of longevity in Drosophila melanogaster. We have found that a hypomorphic mutation of Tequila (Teq(f01792)), as well as cell-specific downregulation of Tequila in insulin-producing neurons of the fly, significantly extends life span. Tequila deficiency-induced life-span extension is likely to be associated with reduced insulin-like signaling, because Tequila mutant flies display several common phenotypes of insulin dysregulation, including reduced circulating Drosophila insulin-like peptide 2 (Dilp2), reduced Akt phosphorylation, reduced body size, and altered glucose homeostasis. These observations suggest that Tequila may confer life-span extension by acting as a modulator of Drosophila insulin-like signaling. PMID- 26265730 TI - Mortality is Written on the Face. AB - BACKGROUND: It is unknown whether facial or surrounding (eg, hair and clothing) cues have the strongest influence on the perceived age of subjects in photographic images, and which drives links between perceived age and survival. METHODS: In 2001, 187 Danish twin pairs (n = 374) aged 70+ years were photographed generating passport-type images. The faces of the twins in these images were swapped creating two new images per twin pair (748 images in total). Ten nurses rated the perceived age of the twin from the original and swapped facial images. The survival of the twins was determined through to the end of 2013. RESULTS: Changing the face or its surrounding significantly changed the perceived age of the images, with only a marginal difference between their effect sizes (difference of 0.5 years, 95% confidence interval CI -0.1 to 1.1). Perceived age, adjusting for chronological age, and sex, was a predictor of survival up to 7 years (hazard ratio 1.17, 95% CI 1.10-1.25) and also 7-12 years (hazard ratio 1.06, 95% CI 1.00-1.12) after the photographs were taken. Where the older looking twin died first they had a significantly older looking face (1.4 years older, 95% CI 0.3-2.6) but not surrounding (0.3 years older, 95% CI -0.8 to 1.4) compared to where the older looking twin died second. CONCLUSIONS: Facial visual cues but not hair or clothing cues drive the link between perceived age and survival. PMID- 26265731 TI - Association of Urinary 6-Sulfatoxymelatonin (aMT6s) Levels and Objective and Subjective Sleep Measures in Older Men: The MrOS Sleep Study. AB - BACKGROUND: Sleep and melatonin have been associated with healthy aging. In this study, we examine the association between melatonin levels and sleep among older men. METHODS: Cross-sectional study of a community-dwelling cohort of 2,821 men aged 65 years or older recruited from six U.S. centers. First morning void urine samples were collected to measure melatonin's major urinary metabolite, 6 sulfatoxymelatonin (aMT6s). We also assessed objective and subjective sleep parameters. We used logistic regression models to calculate multivariate (MV) odds ratios (ORs), and 95% confidence intervals (CIs) adjusted for important demographic variables and comorbidities. RESULTS: In the overall sample, the only significant finding in fully adjusted models was that aMT6s levels were inversely associated with subjectively measured daytime sleepiness (sleepiness mean score of 5.79 in the top aMT6s quartile, and 6.26 in the bottom aMT6s quartile, MV OR, 1.32; 95% CI, 0.95-1.84; p trend <= .02). When restricting to men without beta blocker use (a known melatonin suppressant), aMT6s levels were significantly associated with shorter sleep time, that is, less than 5 hours (MV OR, = 1.90; 95% CI, 1.21-2.99; p trend = .01), and worse sleep efficiency, that is, less than 70% (MV OR, 1.58; 95% CI, 1.28-2.65; p trend < .001). aMT6s were not associated with subjective sleep quality or respiratory disturbance in any of our analyses. CONCLUSION: Lower nocturnal melatonin levels were associated with worsened daytime sleepiness, sleep efficiency, and shorter sleep time in older men. The role of circadian interventions, and whether melatonin levels are a modifiable risk factor for poor sleep in older men, warrants further study. PMID- 26265733 TI - Choice architecture interventions for increased vegetable intake and behaviour change in a school setting: a systematic review. AB - AIMS: The primary objective of this review is to assess the prevalence and quality of published studies on the effect of choice architectural nudge interventions promoting vegetable consumption among adolescents. Additionally, this review aims to identify studies estimating adolescents' attitude towards choice architectural nudge interventions. METHODS: Web of Science, Scopus and PubMed were searched systematically for experimental studies with a predefined search strategy in the period November-December 2013. Publications were included following predetermined inclusion criteria. Studies were evaluated as of high, moderate or weak quality. Finally, studies were grouped by the type of intervention and underwent a narrative synthesis. RESULTS: The search showed that only very few studies investigated the effects of choice architectural nudging interventions on vegetable consumption, and none of them had attitude towards behavioural interventions as an outcome measure. Twelve studies met the inclusion criteria. The results of the 12 studies were inconclusive, and the majority of studies were of weak or moderate quality. CONCLUSION: This review uncovers a gap in knowledge on the effect of choice architectural nudge interventions aiming to promote the intake of vegetables among adolescents in a school context. It also highlights that no previous studies have considered the attitudes towards choice architectural nudge interventions as a potential factor for their success - or lack thereof - in achieving the desired goal of increased vegetable consumption. PMID- 26265732 TI - Antihypertensive Use and Recurrent Falls in Community-Dwelling Older Adults: Findings From the Health ABC Study. AB - BACKGROUND: Despite wide-spread use of antihypertensives in older adults, the literature is unclear about their association with incident recurrent falls over time. METHODS: Health, Aging and Body Composition study participants (n = 2,948) who were well functioning at baseline (1997) were followed to Year 7 (2004). The main outcome was recurrent falls (>=2) in the ensuing 12 months. Antihypertensive use was examined as: (a) any versus none, (b) long- versus short-term (>=2 vs <2 years), and by (c) summated standardized daily dose (SDD; 1 = maximum recommended daily dose for one antihypertensive), and (d) subclass. RESULTS: Controlling for potential demographic, health status/behavior and access to care confounders, we found no increase in risk of recurrent falls in antihypertensive users compared to nonusers (adjusted odds ratio [AOR] = 1.13; 95% CI = 0.88-1.46), or those taking higher SDDs or for longer durations. Only those using a loop diuretic were found to have a modest increased risk of recurrent falls (AOR = 1.50; 95% CI = 1.11-2.03). CONCLUSIONS: Antihypertensive use overall was not statistically significantly associated with recurrent falls after adjusting for important confounders. Loop diuretic use may be associated with recurrent falls and needs further study. PMID- 26265734 TI - Alcohol service provision for older people in an area experiencing high alcohol use and health inequalities. AB - BACKGROUND: UK society is ageing. Older people who drink alcohol, drink more than those from previous generations, drink more frequently than other age groups and are more likely to drink at home and alone. Alcohol problems in later life however are often under-detected and under-reported meaning older people experiencing alcohol problems have high levels of unmet need. METHODS: This study sought to identify existing services within South of Tyne, North East England to capture the extent of service provision for older drinkers and identify any gaps. The Age UK definition of 'older people' (aged 50 and over) was used. Services were contacted by telephone, managers or their deputy took part in semi structured interviews. FINDINGS: Forty six service providers were identified. Only one provided a specific intervention for older drinkers. Others typically provided services for age 18+. Among providers, there was no definitive definition of an older person. Data collection procedures within many organisations did not enable them to confirm whether older people were accessing services. Where alcohol was used alongside other drugs, alcohol use could remain unrecorded. CONCLUSION: To enable alcohol services to meet the needs of older people, greater understanding is needed of the patterns of drinking in later life, the experiences of older people, the scale and scope of the issue and guidance as to the most appropriate action to take. An awareness of the issues related to alcohol use in later life also needs to be integrated into commissioning of other services that impact upon older people. PMID- 26265735 TI - White blood cell and platelet count as adjuncts to standard clinical evaluation for risk assessment in patients at low probability of acute aortic syndrome. AB - AIMS: Pre-test probability assessment is key in the approach to suspected acute aortic syndromes (AASs). However, most patients with AAS-compatible symptoms are classified at low probability, warranting further evaluation for decision on aortic imaging. White blood cell count, platelet count and fibrinogen explore pathophysiological pathways mobilized in AASs and are routinely assayed in the workup of AASs. However, the diagnostic performance of these variables for AASs, alone and as a bundle, is unknown. We tested the hypothesis that white blood cell count, platelet count and/or fibrinogen at presentation may be applied as additional tools to standard clinical evaluation for pre-test risk assessment in patients at low probability of AAS. METHODS AND RESULTS: This was a retrospective observational study conducted on consecutive patients managed in our Emergency Department from 2009 to 2014 for suspected AAS. White blood cell count, platelet count and fibrinogen were assayed during evaluation in the Emergency Department. The final diagnosis was obtained by computed tomography angiography. The pre-test probability of AAS was defined according to guidelines. Of 1210 patients with suspected AAS, 1006 (83.1%) were classified at low probability, and 271 (22.4%) were diagnosed with AAS. Within patients at low probability, presence of at least one alteration among white blood cell count >9*103/ul, platelet count <200*103/ul and fibrinogen <350 mg/dl was associated with a sensitivity of 95.5% (89.7-98.5%) and a specificity of 18.3% (15.6-21.2%). In patients at low probability, white blood cell count >9*103/ul and platelet count <200*103/ul were found as independent predictors of AAS beyond established clinical risk markers. Within patients at low probability, the estimated risk of AAS based on the number of alterations amongst white blood cell count >9*103/ul and platelet count <200*103/ul was 2.7% (1.2-5.7%) with zero alterations, 11.3% (8.8-14.3%) with one alteration and 31.9% (24.8-40%) with two alterations ( p<0.001). CONCLUSION: In addition to standard clinical evaluation, white blood cell count and platelet count may be used in patients at low pre-test probability to fine-tune risk assessment of AAS. PMID- 26265736 TI - Editor's Choice-The role of the emergency department in the management of acute heart failure: An international perspective on education and research. AB - Emergency departments are a major entry point for the initial management of acute heart failure (AHF) patients throughout the world. The initial diagnosis, management and disposition - the decision to admit or discharge - of AHF patients in the emergency department has significant downstream implications. Misdiagnosis, under or overtreatment, or inappropriate admission may place patients at increased risk for adverse events, and add costs to the healthcare system. Despite the critical importance of initial management, data are sparse regarding the impact of early AHF treatment delivered in the emergency department compared to inpatient or chronic heart failure management. Unfortunately, outcomes remain poor, with nearly a third of patients dying or re-hospitalised within 3 months post-discharge. In the absence of robust research evidence, consensus is an important source of guidance for AHF care. Thus, we convened an international group of practising emergency physicians, cardiologists and advanced practice nurses with the following goals to improve outcomes for AHF patients who present to the emergency department or other acute care setting through: (a) a better understanding of the pathophysiology, presentation and management of the initial phase of AHF care; (b) improving initial management by addressing knowledge gaps between best practices and current practice through education and research; and PMID- 26265737 TI - Injectable anaesthesia for adult cat and kitten castration: effects of medetomidine, dexmedetomidine and atipamezole on recovery. AB - Objectives Rapid recovery from injectable anaesthesia benefits cat shelter neutering programmes. The effects of medetomidine, dexmedetomidine and atipamezole on recovery were evaluated in adult cats and kittens (?6 months old). Methods One hundred healthy male cats (age range 2-66 months, weight range 0.7 5.3 kg) admitted forneutering were randomly allocated to groups of 25. Anaesthesia was induced with 60 mg/m2 ketamine, 180 ug/m2 buprenorphine, 3 mg/m2 midazolam and either 600 ug/m2 medetomidine (groups M and MA) or 300 ug/m2 dexmedetomidine (groups D and DA) intramuscularly (IM). Groups MA and DA also received 1.5 mg/m2 atipamezole IM after 40 mins. Preparation time, surgical time, and times to sternal recumbency and standing were recorded. Data were analysed using the Kruskall-Wallis test, unpaired t-tests and ANOVA. Statistical significance was deemed to be P ?0.05. Results Groups did not differ significantly in age, body weight, preparation or surgical time. The time to sternal recumbency in group MA (64 +/- 34 mins) was less than in group M (129 +/- 32 mins), and in group DA it was less than in group D (54 +/- 6 mins vs 110 +/- 27 mins) ( P <0.001). There were no differences in duration of recovery to sternal recumbency between groups M and D or MA and DA. The time to standing in group MA (79 +/- 51 mins) was less than in group M (150 +/- 38 mins) ( P <0.001), and in group DA it was less than in group D (70 +/- 22 mins vs 126 +/- 27 mins) ( P <0.01). Time to standing in group D (126 +/- 27 mins) was less than in group M (150 +/- 38 mins) (P <0.05). Time to standing in groups DA and MA were not different. Kittens recovered faster than adults after atipamezole. Minimal adverse effects were seen. Conclusions and relevance Atipamezole reliably reduced recovery time after anaesthesia incorporating either dexmedetomidine or medetomidine; however, the choice of dexmedetomidine or medetomidine had little effect. Recovery was faster in kittens. PMID- 26265738 TI - Slipped capital femoral epiphysis in 17 Maine Coon cats. AB - Objectives From May 2009 to January 2015, 208 Maine Coon cats presented to the Tierklinik Hollabrunn - a small animal referral and first-opinion centre - and 17 (8.17%) cats were diagnosed with a slipped capital femoral epiphysis (SCFE). Over the same time period, 29 (0.67%) of 4348 cats (all breeds) were diagnosed with SCFE. Methods Clinical and orthopaedic examinations and diagnostic imaging were performed on all affected Maine Coons. Age at first presentation, sex, body weight, body condition score (BCS), unilateral or bilateral manifestation of the disease, activity level and duration of lameness, age at neutering and known family history of disease were recorded. Sixteen of 17 Maine Coons were surgically treated. Surgically removed femoral tissue samples were histologically examined in 13 cases. Results The mean age at first presentation was 21.47 months; male to female ratio was 16:1; mean body weight was 7.5 kg (range 5.3-9.3 kg); and mean BCS was 5.06/9.0. Seven cats were bilaterally affected; the median duration of decreased activity level and lameness was 2 weeks; mean age at neutering was 7.7 months (range 3.0-12.0 months); and four cats were littermates. Fourteen femoral head and neck ostectomies, eight total hip replacements and one primary fixation were performed. All 13 histologically available samples confirmed the diagnosis of SCFE. Conclusions and relevance To date, SCFE has been reported only occasionally in Maine Coon cats. However, the results of this study showed that Maine Coons were approximately 12-fold more likely to develop SCFE than the overall population of cats presenting to the Tierklinik Hollabrunn over the same time period. Male sex, neutering, delayed physeal closure and breed specific high body weight may play an important role in the pathogenesis of SCFE in Maine Coon cats. PMID- 26265739 TI - Need for proper trial protocols to assess side effects of drugs. PMID- 26265740 TI - A case of pulmonary Serratia marcescens granuloma radiologically mimicking metastatic malignancy and tuberculosis infection. AB - Serratia marcescens is a saprophytic gram-negative bacillus capable of causing a wide range of infections. A 57-year-old female was admitted to our hospital for four weeks with community acquired pneumonia. A chest x-ray, six weeks after discharge, demonstrated multiple, bilateral 'cannon ball'-like opacities and mediastinal lymphadenopathy which were highly suspicious of disseminated malignancy or tuberculosis. The only symptom that this patient had was a productive cough. She had multiple commodities, but no specific immunodeficiency disorder. Interestingly, her sputum and bronchial washing samples grew S. marcescens. The computed tomography-guided lung biopsy demonstrated necrotic granulomatous changes. There was no pathological evidence of tuberculosis or fungal infection, malignancy or vasculitis. There are only a handful of reported cases of Serratia granulomas. Thus, we are reporting a rare instance of pulmonary Serratia marcescens granuloma radiologically mimicking metastatic malignancy and tuberculosis infection. PMID- 26265741 TI - Combined Contribution of Increased Intestinal Permeability and Inhibited Deglycosylation of Ginsenoside Rb1 in the Intestinal Tract to the Enhancement of Ginsenoside Rb1 Exposure in Diabetic Rats after Oral Administration. AB - Panax ginseng is becoming a promising antidiabetic herbal medication. As the main active constituents of Panax ginseng, ginsenosides are well known, poorly absorbed chemicals. However, the pharmacokinetic behavior of ginsenosides under diabetic conditions is not fully understood. This study aimed to explore the alterations and potential mechanisms of pharmacokinetic behavior of ginsenoside Rb1 in diabetic rats compared with normal rats and rats fed a high-fat diet. Systemic exposure (area under the concentration-time curve extrapolated from zero to infinity) was significantly increased in diabetic rats after oral administration of Rb1. Oral bioavailability of Rb1 was significantly higher in diabetic rats (2.25%) compared with normal rats (0.90%) and rats fed a high-fat diet (0.78%). Further studies revealed that increased Rb1 exposure in diabetic rats may be mainly attributed to increased Rb1 absorption via the intestine and inhibited Rb1 deglycosylation by the intestinal microflora. Neither metabolic enzymes nor drug transporters displayed appreciable effects on Rb1 disposition. The transport of paracellular markers (fluorescein sodium and fluorescein isothiocyanate-dextran of 4 kDa) as well as Rb1 itself across the Caco-2 monolayer cultured with diabetic serum was promoted, demonstrating that increased paracellular permeability of the Caco-2 monolayer may benefit intestinal Rb1 absorption. In addition, Rb1 exposure was decreased in diabetic rats after Rb1 intravenous administration, which may result from increased Rb1 urinary excretion. In conclusion, Rb1 oral exposure was significantly increased under diabetic conditions, which is of positive significance to clinical treatment. The potential mechanism may be associated with the combined contribution of increased gut permeability and inhibited deglycosylation of ginsenoside Rb1 by intestinal microflora. PMID- 26265742 TI - Defining Human Pathways of Drug Metabolism In Vivo through the Development of a Multiple Humanized Mouse Model. AB - Variability in drug pharmacokinetics is a major factor in defining drug efficacy and side effects. There remains an urgent need, particularly with the growing use of polypharmacy, to obtain more informative experimental data predicting clinical outcomes. Major species differences in multiplicity, substrate specificity, and regulation of enzymes from the cytochrome P450-dependent mono-oxygenase system play a critical role in drug metabolism. To develop an in vivo model for predicting human responses to drugs, we generated a mouse, where 31 P450 genes from the Cyp2c, Cyp2d, and Cyp3a gene families were exchanged for their relevant human counterparts. The model has been improved through additional humanization for the nuclear receptors constitutive androgen receptor and pregnane X receptor that control the expression of key drug metabolizing enzymes and transporters. In this most complex humanized mouse model reported to date, the cytochromes P450 function as predicted and we illustrate how these mice can be applied to predict drug-drug interactions in humans. PMID- 26265743 TI - A Screen of Approved Drugs Identifies the Androgen Receptor Antagonist Flutamide and Its Pharmacologically Active Metabolite 2-Hydroxy-Flutamide as Heterotropic Activators of Cytochrome P450 3A In Vitro and In Vivo. AB - Once thought to be an artifact of microsomal systems, atypical kinetics with cytochrome P450 (CYP) enzymes have been extensively investigated in vitro and found to be substrate and species dependent. Building upon increasing reports of heterotropic CYP activation and inhibition in clinical settings, we screened a compound library of clinically approved drugs and various probe compounds to identify the frequency of heterotropism observed with different drug classes and the associated CYP enzymes thereof (1A2, 2C9, 2D6, and 3A4/5). Results of this screen revealed that the prescribed androgen receptor antagonist flutamide activated the intrinsic midazolam hydroxylase activity of CYP3A in human hepatic microsomes (66%), rat and human hepatocytes (36 and 160%, respectively), and in vivo in male Sprague-Dawley rats (>2-fold, combined area under the curve of primary rat in vivo midazolam metabolites). In addition, a screen of the pharmacologically active metabolite 2-hydroxy-flutamide revealed that this principle metabolite increased CYP3A metabolism of midazolam in human microsomes (30%) and hepatocytes (110%). Importantly, both flutamide and 2-hydroxy-flutamide demonstrated a pronounced increase in the CYP3A-mediated metabolism of commonly paired medications, nifedipine (antihypertensive) and amiodarone (antiarrhythmic), in multispecies hepatocytes (100% over baseline). These data serve to highlight the importance of an appropriate substrate and in vitro system selection in the pharmacokinetic modeling of atypical enzyme kinetics. In addition, the results of our investigation have illuminated a previously undiscovered class of heterotropic CYP3A activators and have demonstrated the importance of selecting commonly paired therapeutics in the in vitro and in vivo modeling of projected clinical outcomes. PMID- 26265744 TI - Inhibition of Anthracycline Alcohol Metabolite Formation in Human Heart Cytosol: A Potential Role for Several Promising Drugs. AB - The clinical efficacy of anthracyclines (e.g., doxorubicin and daunorubicin) in cancer therapy is limited by their severe cardiotoxicity, the etiology of which is still not fully understood. The development of anthracycline-induced cardiomyopathy has been found to correlate with myocardial formation and accumulation of anthracycline secondary alcohol metabolites (e.g., doxorubicinol and daunorubicinol) that are produced by distinct cytosolic NADPH-dependent reductases. The aim of the current study is to identify chemical compounds capable of inhibiting myocardial reductases implied in anthracycline reductive metabolism in an attempt to decrease the production of cardiotoxic C-13 alcohol metabolites. Among the variety of tested compounds (metal chelators, radical scavengers, antioxidants, beta-blockers, nitrone spin traps, and lipid-lowering drugs), ebselen, cyclopentenone prostaglandins, nitric oxide donors, and short chain coenzyme Q analogs resulted in being effective inhibitors of both doxorubicinol and daunorubicinol formation. In particular, ebselen (as well as ebselen diselenide, its storage form in the cells) was the most potent inhibitor of cardiotoxic anthracycline alcohol metabolites with 50% inhibition of doxorubicinol formation at 0.2 mol Eq of ebselen with respect to doxorubicin concentration. The high efficacy, together with its favorable pharmacological profile (low toxicity, lack of adverse effects, and metabolic stability) portends ebselen as a promising cardioprotective agent against anthracycline-induced cardiotoxicity. PMID- 26265745 TI - Immediate delivery in women with non-severe hypertensive disorders at 34-37 weeks' gestation does not reduce maternal complications, and increases neonatal risks more than under expectant management. PMID- 26265746 TI - Intermittent electrical stimulation of the right cervical vagus nerve in salt sensitive hypertensive rats: effects on blood pressure, arrhythmias, and ventricular electrophysiology. AB - Hypertension (HTN) is the single greatest risk factor for potentially fatal cardiovascular diseases. One cause of HTN is inappropriately increased sympathetic nervous system activity, suggesting that restoring the autonomic nervous balance may be an effective means of HTN treatment. Here, we studied the potential of vagus nerve stimulation (VNS) to treat chronic HTN and cardiac arrhythmias through stimulation of the right cervical vagus nerve in hypertensive rats. Dahl salt-sensitive rats (n = 12) were given a high salt diet to induce HTN. After 6 weeks, rats were randomized into two groups: HTN-Sham and HTN-VNS, in which VNS was provided to HTN-VNS group for 4 weeks. In vivo blood pressure and electrocardiogram activities were monitored continuously by an implantable telemetry system. After 10 weeks, rats were euthanized and their hearts were extracted for ex vivo electrophysiological studies using high-resolution optical mapping. Six weeks of high salt diet significantly increased both mean arterial pressure (MAP) and pulse pressure, demonstrating successful induction of HTN in all rats. After 4 weeks of VNS treatment, the increase in MAP and the number of arrhythmia episodes in HTN-VNS rats was significantly attenuated when compared to those observed in HTN-Sham rats. VNS treatment also induced changes in electrophysiological properties of the heart, such as reduction in action potential duration (APD) during rapid drive pacing, slope of APD restitution, spatial dispersion of APD, and increase in conduction velocity of impulse propagation. Overall, these results provide further evidence for the therapeutic efficacy of VNS in HTN and HTN-related heart diseases. PMID- 26265747 TI - Methylglyoxal-derived hydroimidazolone residue of plasma protein can behave as a predictor of prediabetes in Spontaneously Diabetic Torii rats. AB - Prediabetes, typically defined as impaired glucose tolerance and/or impaired fasting blood glucose, is a high-risk state of developing diabetes. The association of diabetes-related metabolites with prediabetes has not been investigated intensively. This study aimed to get insights into the metabolic behaviors of some typical diabetes-related metabolites in plasma of male Spontaneously Diabetic Torii (SDT) rats during pathogenic progress of diabetes and to assess in vivo if the variation in these metabolites related to the progression of prediabetic stage. To address this question, SDT rats and Sprague Dawley (SD) rats as control were maintained from the age of 7 to 25 weeks. Five typical advanced glycation end products (AGEs) residue of plasma protein and their free adducts were determined by liquid chromatography with tandem mass detection over the duration of the investigation. The SDT rats exhibited impaired glucose tolerance since the age of 12 weeks and developed diabetes with significantly elevated fasting glucose levels after 22 weeks. At the prediabetic stage (12-21 weeks), no significant differences were observed on AGE-free adducts levels of SDT rats compared with SD rats. However, methylglyoxal-derived hydroimidazolone (MG-H1) residue contents of plasma protein were significantly elevated in SDT rats at the age of 16 weeks, whereas other AGE residues of plasma protein did not show marked difference. The present study has revealed significant increase in MG-H1 residue content of plasma protein at the prediabetic stage of a spontaneously diabetic rat model, irrespective of unaltered fasting blood glucose and constant plasma levels of other AGEs. PMID- 26265748 TI - Perilipin 4 in human skeletal muscle: localization and effect of physical activity. AB - Perilipins (PLINs) coat the surface of lipid droplets and are important for the regulation of lipid turnover. Knowledge about the physiological role of the individual PLINs in skeletal muscle is limited although lipid metabolism is very important for muscle contraction. To determine the effect of long-term exercise on PLINs expression, 26 middle-aged, sedentary men underwent 12 weeks combined endurance and strength training intervention. Muscle biopsies from m. vastus lateralis and subcutaneous adipose tissue were taken before and after the intervention and total gene expression was measured with deep mRNA sequencing. PLIN4 mRNA exhibited the highest expression of all five PLINs in both tissues, and the expression was significantly reduced after long-term exercise in skeletal muscle. Moreover, PLIN4 mRNA expression levels in muscle correlated with the expression of genes involved in de novo phospholipid biosynthesis, with muscular content of phosphatidylethanolamine and phosphatidylcholine, and with the content of subsarcolemmal lipid droplets. The PLIN4 protein was mainly located at the periphery of skeletal muscle fibers, with higher levels in slow-twitch as compared to fast-twitch skeletal muscle fibers. In summary, we report reduced expression of PLIN4 after long-term physical activity, and preferential slow twitch skeletal muscle fibers and plasma membrane-associated PLIN4 location. PMID- 26265749 TI - Systemic adaptation of lipid metabolism in response to low- and high-fat diet in Nile tilapia (Oreochromis niloticus). AB - Natural selection endows animals with the abilities to store lipid when food is abundant and to synthesize lipid when it is limited. However, the relevant adaptive strategy of lipid metabolism has not been clearly elucidated in fish. This study examined the systemic metabolic strategies of Nile tilapia to maintain lipid homeostasis when fed with low- or high-fat diets. Three diets with different lipid contents (1%, 7%, and 13%) were formulated and fed to tilapias for 10 weeks. At the end of the feeding trial, the growth rate, hepatic somatic index, and the triglyceride (TG) contents of serum, liver, muscle, and adipose tissue were comparable among three groups, whereas the total body lipid contents and the mass of adipose tissue increased with the increased dietary lipid levels. Overall quantitative PCR, western blotting and transcriptomic assays indicated that the liver was the primary responding organ to low-fat (LF) diet feeding, and the elevated glycolysis and accelerated biosynthesis of fatty acids (FA) in the liver is likely to be the main strategies of tilapia toward LF intake. In contrast, excess ingested lipid was preferentially stored in adipose tissue through increasing the capability of FA uptake and TG synthesis. Increasing numbers, but not enlarging size, of adipocytes may be the main strategy of Nile tilapia responding to continuous high-fat (HF) diet feeding. This is the first study illuminating the systemic adaptation of lipid metabolism responding to LF or HF diet in fish, and our results shed new light on fish physiology. PMID- 26265750 TI - Lack of independent effect of type 2 diabetes beyond characteristic comorbidities and medications on small muscle mass exercising muscle blood flow and exercise tolerance. AB - Persons with type 2 diabetes (T2D) are believed to have reduced exercise tolerance; this may be partly due to impaired exercising muscle blood flow (MBF). Whether there is an impact of T2D on exercising MBF within the typical constellation of comorbidities (hypertension, dyslipidemia, obesity) and their associated medications has not been investigated. We tested the hypothesis that small muscle mass exercise tolerance is reduced in persons with T2D versus Controls (matched for age, body mass index, fitness, comorbidities, non-T2D medications) and that this is related to blunted MBF. Eight persons with T2D and eight controls completed a forearm critical force (fCFimpulse) test as a measure of exercise tolerance (10-min intermittent maximal effort forearm contractions; the average contraction impulse in the last 30 sec quantified fCFimpulse). Forearm blood flow (FBF; ultrasound) and mean arterial pressure (MAP; finger photoplethysmography) were measured; forearm vascular conductance (FVK) was calculated. Data are means +/- SD, T2D versus Control. fCFimpulse was not different between groups (136.9 +/- 47.3 N.sec vs. 163.1 +/- 49.7 N.sec, P = 0.371) nor was the ?FBF from rest to during exercise at fCFimpulse (502.9 +/- 144.6 vs. 709.1 +/- 289.2 mL/min, P = 0.092), or its determinants ?FVK and ?MAP (both P > 0.05), although there was considerable interindividual variability. ?FBF was strongly related to fCFimpulse (r = 0.727, P = 0.002), providing support for the relationship between oxygen delivery and exercise tolerance. We conclude that small muscle mass exercising MBF and exercise tolerance are not impaired in representative persons with T2D versus appropriately matched controls. This suggests that peripheral vascular control impairment does not contribute to reduced exercise tolerance in this population. PMID- 26265751 TI - Ovariectomy results in differential shifts in gut microbiota in low versus high aerobic capacity rats. AB - The increased risk for cardiometabolic disease with the onset of menopause is widely studied and likely precipitated by the decline in endogenous estradiol (E2), yet the precise mechanisms are unknown. The gut microbiome is involved in estrogen metabolism and has been linked to metabolic disease, suggesting its potential involvement in the postmenopausal phenotype. Furthermore, menopause associated risk factors, as well as gut ecology, are altered with exercise. Therefore, we studied microbial changes in an ovariectomized (OVX vs. Sham) rat model of high (HCR) and low (LCR) intrinsic aerobic capacity (n = 8-10/group) in relation to changes in body weight/composition, glucose tolerance, and liver triglycerides (TG). Nine weeks after OVX, HCR rats were moderately protected against regional adipose tissue gain and liver TG accumulation (P < 0.05 for both). Microbial diversity and number of the Bacteroidetes phylum were significantly increased in LCR with OVX, but unchanged in HCR OVX relative to Sham. Plasma short-chain fatty acids (SCFA), produced by bacteria in the gut and recognized as metabolic signaling molecules, were significantly greater in HCR Sham relative to LCR Sham rats (P = 0.05) and were decreased with OVX in both groups. These results suggest that increased aerobic capacity may be protective against menopause-associated cardiometabolic risk and that gut ecology, and production of signaling molecules such as SCFA, may contribute to the mediation. PMID- 26265752 TI - Seasonal variation in muscle sympathetic nerve activity. AB - Epidemiologic data suggest there are seasonal variations in the incidence of severe cardiac events with peak levels being evident in the winter. Whether autonomic indices including muscle sympathetic nerve activity (MSNA) vary with season remains unclear. In this report, we tested the hypothesis that resting MSNA varies with the seasons of the year with peak levels evident in the winter. We analyzed the supine resting MSNA in 60 healthy subjects. Each subject was studied during two, three, or four seasons (total 237 visits). MSNA burst rate in the winter (21.0 +/- 6.8 burst/min, mean +/- SD) was significantly greater than in the summer (13.5 +/- 5.8 burst/min, P < 0.001), the spring (17.1 +/- 9.0 burst/min, P = 0.03), and the fall (17.9 +/- 7.7 burst/min, P = 0.002). There was no significant difference in MSNA for other seasonal comparisons. The results suggest that resting sympathetic nerve activity varies along the seasons, with peak levels evident in the winter. We speculate that the seasonal changes in sympathetic activity may be a contribution to the previously observed seasonal variations in cardiovascular morbidity and mortality. PMID- 26265753 TI - Low-load resistance training during step-reduction attenuates declines in muscle mass and strength and enhances anabolic sensitivity in older men. AB - Step-reduction (SR) in older adults results in muscle atrophy and an attenuated rise in postprandial muscle protein synthesis (MPS): anabolic resistance. Knowing that resistance exercise (RT) can enhance MPS, we examined whether RT could enhance MPS following 2 weeks of SR. In addition, as we postulated that SR may impair feeding-induced vasodilation limiting nutrient delivery to muscle, we also examined whether citrulline (CIT), as an arginine and nitric oxide precursor, could attenuate muscle anabolic resistance accompanying SR. We used a unilateral leg model to compare older subjects' who had undergone SR to a loaded condition of SR plus RT (SR + RT). Thirty older men (70 +/- 1 years) underwent 14 days of SR (<1500 steps/day) with supplementation of either 5 g/day CIT or glycine placebo. Throughout SR, subjects performed unilateral low-load RT thrice weekly. We assessed muscle protein synthesis in the postabsorptive and postprandial state (20 g whey isolate plus 15 g glycine or as micellar-whey with 5 g CIT or 15 g glycine, n = 10/group). As MPS was similar after ingestion of either whey isolate, micellar-whey, or micellar-whey + CIT data related to different dietary groups were collapsed to compare SR and SR + RT legs. Subjects' daily steps were reduced by 80 +/- 2% during SR (P < 0.001) compared with baseline. Leg fat-free mass decreased with SR (-124 +/- 61 g) and increased in the SR + RT (+126 +/- 68 g; P = 0.003). Myofibrillar FSR was lower (P < 0.0001) in the SR as compared with the SR + RT leg in the postabsorptive (0.026 +/- 0.001%/h vs. 0.045 +/- 0.001%/h) and postprandial states (0.055 +/- 0.002%/h vs. 0.115 +/- 0.003%/h). We conclude that low-load RT, but not supplementation with CIT, can attenuate the deleterious effects of SR in aging muscle. PMID- 26265754 TI - Seasonal influence over serum and urine metabolic markers in submariners during prolonged patrols. AB - Within the framework of earlier publications, we have consistently dedicated our investigations to eliciting the effects of both seasonal vitamin D deficiency and submarine-induced hypercapnia on serum parameters for acid-base balance and bone metabolism in submariners over a 2-month winter (WP) or summer (SP) patrols. The latest findings reported herein, contribute further evidence with regard to overall physiological regulations in the same submariner populations that underwent past scrutiny. Hence, urine and blood samples were collected in WP and SP submariners at control prepatrol time as well as on submarine patrol days 20, 41, and 58. Several urine and serum metabolic markers were quantified, namely, deoxypyridinoline (DPD), lactate, albumin, creatinine, nonesterified fatty acids (NEFA), and ionized sodium (Na(+)) or potassium (K(+)), with a view to assessing bone, muscle, liver, or kidney metabolisms. We evidenced bone metabolism alteration (urine DPD, calcium, and phosphorus) previously recorded in submarine crewmembers under prolonged patrols. We also highlighted transitory modifications in liver metabolism (serum albumin) occurring within the first 20 days of submersion. We further evidenced changes in submariners' renal physiology (serum creatinine) throughout the entire patrol time span. Measurements of ionic homeostasis (serum Na(+) and K(+)) displayed potential seasonal impact over active ionic pumps in submariners. Finally, there is some evidence that submersion provides beneficial conditions prone to fend off seasonal lactic acidosis (serum lactate) detected in WP submariners. PMID- 26265755 TI - Impact of periconceptional and preimplantation undernutrition on factors regulating myogenesis and protein synthesis in muscle of singleton and twin fetal sheep. AB - In this study, we determined the effect of maternal undernutrition in the periconceptional (PCUN: ~80 days before to 6 days after conception) and preimplantation (PIUN: 0-6 days after conception) periods on the mRNA and protein abundance of key factors regulating myogenesis and protein synthesis, and on the relationship between the abundance of these factors and specific microRNA expression in the quadriceps muscle of singleton and twin fetal sheep at 135-138 days of gestation. PCUN and PIUN resulted in a decrease in the protein abundance of MYF5, a factor which determines the myogenic lineage, in singletons and twins. Interestingly, there was a concomitant increase in insulin-like growth factor-1 mRNA expression, a decrease in the protein abundance of the myogenic inhibitor, myostatin (MSTN), and an increase in the mRNA and protein abundance of the MSTN inhibitor, follistatin (FST), in the PCUN and PIUN groups in both singletons and twins. These promyogenic changes may compensate for the decrease in MYF5 protein abundance evoked by early embryonic undernutrition. PCUN and PIUN also increased the protein abundance of phosphorylated eukaryotic translation initiation factor binding protein 1 (EIF4EBP1; T70 and S65) in fetal muscle in singletons and twins. There was a significant inverse relationship between the expression of miR 30a-5p, miR-30d-5p, miR-27b-3p, miR106b-5p, and miR-376b and the protein abundance of mechanistic target of rapamycin (MTOR), FST, or MYF5 in singletons or twins. In particular, the expression of miR-30a-5p was increased and MYF5 protein abundance was decreased, in PCUN and PIUN twins supporting the conclusion that the impact of PCUN and PIUN is predominantly on the embryo. PMID- 26265756 TI - Local chemerin levels are positively associated with DSS-induced colitis but constitutive loss of CMKLR1 does not protect against development of colitis. AB - Inflammatory bowel disease (IBD) is a family of disorders including ulcerative colitis and Crohn's disease that are characterized by chronic and relapsing intestinal inflammation. Increased production of proinflammatory mediators, possibly combined with low expression of anti-inflammatory mediators, is thought to promote the development and progression of IBD. In the current study, we demonstrate that expression, secretion, and processing of chemerin, a potent chemoattractant for cells expressing chemokine-like receptor 1 (CMKLR1), increased in the cecum and colon along a gradient positively associated with the severity of inflammation in dextran sodium sulfate (DSS)-induced colitis. We also show that levels of circulating bioactive chemerin increased following DSS treatment. At both 6-8 and 14-16 weeks of age, CMKLR1 knockout mice developed signs of clinical illness more slowly than wild type and had changes in circulating cytokine levels, increased spleen weight, and increased local chemerin secretion following DSS treatment. However, knockout mice ultimately developed similar levels of clinical illness and local inflammation as wild type. Finally, contrary to previous reports, intraperitoneal injection of bioactive chemerin had no effect on the severity of DSS-induced colitis. This suggests that local chemerin levels have a greater impact than circulating levels in the pathogenesis of colitis. Considered altogether, bioactive chemerin represents a novel biomarker for IBD severity, although strategies to modulate endogenous chemerin signaling other than chronic CMKLR1 loss are necessary in order to exploit chemerin as a therapeutic target for the treatment of IBD. PMID- 26265757 TI - Response to the letter: role of remote ischemic preconditioning against acute mountain sickness during early phase by Sikri and Chawla. PMID- 26265758 TI - Role of remote ischemic preconditioning against acute mountain sickness during early phase. PMID- 26265759 TI - The development of hepatic stellate cells in normal and abnormal human fetuses - an immunohistochemical study. AB - The precise embryological origin and development of hepatic stellate cells is not established. Animal studies and observations on human fetuses suggest that they derive from posterior mesodermal cells that migrate via the septum transversum and developing diaphragm to form submesothelial cells beneath the liver capsule, which give rise to mesenchymal cells including hepatic stellate cells. However, it is unclear if these are similar to hepatic stellate cells in adults or if this is the only source of stellate cells. We have studied hepatic stellate cells by immunohistochemistry, in developing human liver from autopsies of fetuses with and without malformations and growth restriction, using cellular Retinol Binding Protein-1 (cRBP-1), Glial Fibrillary Acidic Protein (GFAP), and alpha-Smooth Muscle Actin (alphaSMA) antibodies, to identify factors that influence their development. We found that hepatic stellate cells expressing cRBP-1 are present from the end of the first trimester of gestation and reduce in density throughout gestation. They appear abnormally formed and variably reduced in number in fetuses with abnormal mesothelial Wilms Tumor 1 (WT1) function, diaphragmatic hernia and in ectopic liver nodules without mesothelium. Stellate cells showed similarities to intravascular cells and their presence in a fetus with diaphragm agenesis suggests they may be derived from circulating stem cells. Our observations suggest circulating stem cells as well as mesothelium can give rise to hepatic stellate cells, and that they require normal mesothelial function for their development. PMID- 26265760 TI - Altering Lignin Composition to Improve Biofuel Production. PMID- 26265761 TI - Conserved Gene Expression Programs in Developing Roots from Diverse Plants. AB - The molecular basis for the origin and diversification of morphological adaptations is a central issue in evolutionary developmental biology. Here, we defined temporal transcript accumulation in developing roots from seven vascular plants, permitting a genome-wide comparative analysis of the molecular programs used by a single organ across diverse species. The resulting gene expression maps uncover significant similarity in the genes employed in roots and their developmental expression profiles. The detailed analysis of a subset of 133 genes known to be associated with root development in Arabidopsis thaliana indicates that most of these are used in all plant species. Strikingly, this was also true for root development in a lycophyte (Selaginella moellendorffii), which forms morphologically different roots and is thought to have evolved roots independently. Thus, despite vast differences in size and anatomy of roots from diverse plants, the basic molecular mechanisms employed during root formation appear to be conserved. This suggests that roots evolved in the two major vascular plant lineages either by parallel recruitment of largely the same developmental program or by elaboration of an existing root program in the common ancestor of vascular plants. PMID- 26265763 TI - X-ray computed tomography to study rice (Oryza sativa L.) panicle development. AB - Computational tomography is an important technique for developing digital agricultural models that may help farmers and breeders for increasing crop quality and yield. In the present study an attempt has been made to understand rice seed development within the panicle at different developmental stages using this technique. During the first phase of cell division the Hounsfield Unit (HU) value remained low, increased in the dry matter accumulation phase, and finally reached a maximum at the maturation stage. HU value and seed dry weight showed a linear relationship in the varieties studied. This relationship was confirmed subsequently using seven other varieties. This is therefore an easy, simple, and non-invasive technique which may help breeders to select the best varieties. In addition, it may also help farmers to optimize post-anthesis agronomic practices as well as deciding the crop harvest time for higher grain yield. PMID- 26265764 TI - Sparse estimation of gene-gene interactions in prediction models. AB - Current assessment of gene-gene interactions is typically based on separate parallel analysis, where each interaction term is tested separately, while less attention has been paid on simultaneous estimation of interaction terms in a prediction model. As the number of interaction terms grows fast, sparse estimation is desirable from statistical and interpretability reasons. There is a large literature on sparse estimation, but there is a natural hierarchy between the interaction and its corresponding main effects that requires special considerations. We describe random-effect models that impose sparse estimation of interactions under both strong and weak-hierarchy constraints. We develop an estimation procedure based on the hierarchical-likelihood argument and show that the modelling approach is equivalent to a penalty-based method, with the advantage of the models being more transparent and flexible. We compare the procedure with some standard methods in a simulation study and illustrate its application in an analysis of gene-gene interaction model to predict body-mass index. PMID- 26265765 TI - Comparison of bias-corrected covariance estimators for MMRM analysis in longitudinal data with dropouts. AB - In longitudinal clinical trials, some subjects will drop out before completing the trial, so their measurements towards the end of the trial are not obtained. Mixed-effects models for repeated measures (MMRM) analysis with "unstructured" (UN) covariance structure are increasingly common as a primary analysis for group comparisons in these trials. Furthermore, model-based covariance estimators have been routinely used for testing the group difference and estimating confidence intervals of the difference in the MMRM analysis using the UN covariance. However, using the MMRM analysis with the UN covariance could lead to convergence problems for numerical optimization, especially in trials with a small-sample size. Although the so-called sandwich covariance estimator is robust to misspecification of the covariance structure, its performance deteriorates in settings with small-sample size. We investigated the performance of the sandwich covariance estimator and covariance estimators adjusted for small-sample bias proposed by Kauermann and Carroll ( J Am Stat Assoc 2001; 96: 1387-1396) and Mancl and DeRouen ( Biometrics 2001; 57: 126-134) fitting simpler covariance structures through a simulation study. In terms of the type 1 error rate and coverage probability of confidence intervals, Mancl and DeRouen's covariance estimator with compound symmetry, first-order autoregressive (AR(1)), heterogeneous AR(1), and antedependence structures performed better than the original sandwich estimator and Kauermann and Carroll's estimator with these structures in the scenarios where the variance increased across visits. The performance based on Mancl and DeRouen's estimator with these structures was nearly equivalent to that based on the Kenward-Roger method for adjusting the standard errors and degrees of freedom with the UN structure. The model-based covariance estimator with the UN structure under unadjustment of the degrees of freedom, which is frequently used in applications, resulted in substantial inflation of the type 1 error rate. We recommend the use of Mancl and DeRouen's estimator in MMRM analysis if the number of subjects completing is ( n + 5) or less, where n is the number of planned visits. Otherwise, the use of Kenward and Roger's method with UN structure should be the best way. PMID- 26265762 TI - Manipulation of Guaiacyl and Syringyl Monomer Biosynthesis in an Arabidopsis Cinnamyl Alcohol Dehydrogenase Mutant Results in Atypical Lignin Biosynthesis and Modified Cell Wall Structure. AB - Modifying lignin composition and structure is a key strategy to increase plant cell wall digestibility for biofuel production. Disruption of the genes encoding both cinnamyl alcohol dehydrogenases (CADs), including CADC and CADD, in Arabidopsis thaliana results in the atypical incorporation of hydroxycinnamaldehydes into lignin. Another strategy to change lignin composition is downregulation or overexpression of ferulate 5-hydroxylase (F5H), which results in lignins enriched in guaiacyl or syringyl units, respectively. Here, we combined these approaches to generate plants enriched in coniferaldehyde-derived lignin units or lignins derived primarily from sinapaldehyde. The cadc cadd and ferulic acid hydroxylase1 (fah1) cadc cadd plants are similar in growth to wild type plants even though their lignin compositions are drastically altered. In contrast, disruption of CAD in the F5H-overexpressing background results in dwarfism. The dwarfed phenotype observed in these plants does not appear to be related to collapsed xylem, a hallmark of many other lignin-deficient dwarf mutants. cadc cadd, fah1 cadc cadd, and cadd F5H-overexpressing plants have increased enzyme-catalyzed cell wall digestibility. Given that these CAD deficient plants have similar total lignin contents and only differ in the amounts of hydroxycinnamaldehyde monomer incorporation, these results suggest that hydroxycinnamaldehyde content is a more important determinant of digestibility than lignin content. PMID- 26265766 TI - A vine copula mixed effect model for trivariate meta-analysis of diagnostic test accuracy studies accounting for disease prevalence. AB - A bivariate copula mixed model has been recently proposed to synthesize diagnostic test accuracy studies and it has been shown that it is superior to the standard generalized linear mixed model in this context. Here, we call trivariate vine copulas to extend the bivariate meta-analysis of diagnostic test accuracy studies by accounting for disease prevalence. Our vine copula mixed model includes the trivariate generalized linear mixed model as a special case and can also operate on the original scale of sensitivity, specificity, and disease prevalence. Our general methodology is illustrated by re-analyzing the data of two published meta-analyses. Our study suggests that there can be an improvement on trivariate generalized linear mixed model in fit to data and makes the argument for moving to vine copula random effects models especially because of their richness, including reflection asymmetric tail dependence, and computational feasibility despite their three dimensionality. PMID- 26265767 TI - An extended sequential goodness-of-fit multiple testing method for discrete data. AB - The sequential goodness-of-fit (SGoF) multiple testing method has recently been proposed as an alternative to the familywise error rate- and the false discovery rate-controlling procedures in high-dimensional problems. For discrete data, the SGoF method may be very conservative. In this paper, we introduce an alternative SGoF-type procedure that takes into account the discreteness of the test statistics. Like the original SGoF, our new method provides weak control of the false discovery rate/familywise error rate but attains false discovery rate levels closer to the desired nominal level, and thus it is more powerful. We study the performance of this method in a simulation study and illustrate its application to a real pharmacovigilance data set. PMID- 26265768 TI - Introducing the fit-criteria assessment plot - A visualisation tool to assist class enumeration in group-based trajectory modelling. AB - Background and objective Group-based trajectory modelling is a model-based clustering technique applied for the identification of latent patterns of temporal changes. Despite its manifold applications in clinical and health sciences, potential problems of the model selection procedure are often overlooked. The choice of the number of latent trajectories (class-enumeration), for instance, is to a large degree based on statistical criteria that are not fail-safe. Moreover, the process as a whole is not transparent. To facilitate class enumeration, we introduce a graphical summary display of several fit and model adequacy criteria, the fit-criteria assessment plot. Methods An R-code that accepts universal data input is presented. The programme condenses relevant group based trajectory modelling output information of model fit indices in automated graphical displays. Examples based on real and simulated data are provided to illustrate, assess and validate fit-criteria assessment plot's utility. Results Fit-criteria assessment plot provides an overview of fit criteria on a single page, placing users in an informed position to make a decision. Fit-criteria assessment plot does not automatically select the most appropriate model but eases the model assessment procedure. Conclusions Fit-criteria assessment plot is an exploratory, visualisation tool that can be employed to assist decisions in the initial and decisive phase of group-based trajectory modelling analysis. Considering group-based trajectory modelling's widespread resonance in medical and epidemiological sciences, a more comprehensive, easily interpretable and transparent display of the iterative process of class enumeration may foster group-based trajectory modelling's adequate use. PMID- 26265769 TI - Bias-corrected estimates for logistic regression models for complex surveys with application to the United States' Nationwide Inpatient Sample. AB - For complex surveys with a binary outcome, logistic regression is widely used to model the outcome as a function of covariates. Complex survey sampling designs are typically stratified cluster samples, but consistent and asymptotically unbiased estimates of the logistic regression parameters can be obtained using weighted estimating equations (WEEs) under the naive assumption that subjects within a cluster are independent. Despite the relatively large samples typical of many complex surveys, with rare outcomes, many interaction terms, or analysis of subgroups, the logistic regression parameters estimates from WEE can be markedly biased, just as with independent samples. In this paper, we propose bias corrected WEEs for complex survey data. The proposed method is motivated by a study of postoperative complications in laparoscopic cystectomy, using data from the 2009 United States' Nationwide Inpatient Sample complex survey of hospitals. PMID- 26265770 TI - Bayesian nonparametric mixed-effects joint model for longitudinal-competing risks data analysis in presence of multiple data features. AB - Recently, the joint analysis of longitudinal and survival data has been an active research area. Most joint models focus on survival data with only one type of failure. The research on joint modeling of longitudinal and competing risks survival data is sparse. Even so, many joint models for this type of data assume parametric function forms for both longitudinal and survival sub-models, thus limits their use. Further, the common data features that are usually observed in practice, such as asymmetric distribution and missingness in response, measurement errors in covariate, need to be taken into account for reliable parameter estimation. The statistical inference is complicated when all these factors are considered simultaneously. In the article, driven by a motivating example, we assume nonparametric function forms for the varying coefficients in both longitudinal and competing risks survival sub-models. We propose a Bayesian nonparametric mixed-effects joint model for the analysis of longitudinal competing risks data with asymmetry, missingness, and measurement errors. Simulation studies are conducted to assess the performance of the proposed method. We apply the proposed method to an AIDS dataset and compare a few candidate models under various settings. Some interesting results are reported. PMID- 26265771 TI - Unbiased estimation for response adaptive clinical trials. AB - Bayesian adaptive trials have the defining feature that the probability of randomization to a particular treatment arm can change as information becomes available as to its true worth. However, there is still a general reluctance to implement such designs in many clinical settings. One area of concern is that their frequentist operating characteristics are poor or, at least, poorly understood. We investigate the bias induced in the maximum likelihood estimate of a response probability parameter, p, for binary outcome by the process of adaptive randomization. We discover that it is small in magnitude and, under mild assumptions, can only be negative - causing one's estimate to be closer to zero on average than the truth. A simple unbiased estimator for p is obtained, but it is shown to have a large mean squared error. Two approaches are therefore explored to improve its precision based on inverse probability weighting and Rao Blackwellization. We illustrate these estimation strategies using two well-known designs from the literature. PMID- 26265772 TI - What Makes a Manuscript Holistic? Revisited and Still Relevant. PMID- 26265774 TI - Drug coated balloon angioplasty in elderly patients with small vessel coronary disease. AB - BACKGROUND: Coronary angioplasty in advanced age is associated with higher rate of comorbidities and complications. Drug coated balloon only angioplasty (DCBA) has emerged as an alternative to treat small vessel coronary disease (SVCD), of reference vessel diameters <2.8 mm, with shorter duration of dual antiplatelet (DAPT). This is the first study to assess the DCBA efficacy in an elderly population with SVCD. METHODS AND RESULTS: We performed a prospective study of 447 patients (334 patients aged <75 and 113 patients aged ?75 years old) acquired from the SeQuent Please Small Vessel 'Paclitaxel-Coated Balloon Only' registry. In the older age group, more patients have hypertension (89% versus 77%; p = 0.006), renal insufficiency (21% versus 6%; p < 0.001), atrial fibrillation (17% versus 7%; p = 0.001), and calcified lesions (33% versus 20%; p = 0.006). At 30 days, there was one myocardial infarction requiring target lesion revascularization (TLR) in the younger group. No major adverse cardiac event (MACE) was observed in the older group. At 9 months, the MACE rate in the younger group was 4.2% and 6.1% in the older group (p = 0.453), with TLR rates at 3.9% and 3.0% (p = 0.704) respectively. There was no cardiac death observed. CONCLUSION: DBCA in the elderly with SVCD is as safe and effective compared with younger patients despite more complex anatomy and comorbidities. PMID- 26265775 TI - Multilayered Regulation of Ethylene Induction Plays a Positive Role in Arabidopsis Resistance against Pseudomonas syringae. AB - Ethylene, a key phytohormone involved in plant-pathogen interaction, plays a positive role in plant resistance against fungal pathogens. However, its function in plant bacterial resistance remains unclear. Here, we report a detailed analysis of ethylene induction in Arabidopsis (Arabidopsis thaliana) in response to Pseudomonas syringae pv tomato DC3000 (Pst). Ethylene biosynthesis is highly induced in both pathogen/microbe-associated molecular pattern (PAMP)-triggered immunity and effector-triggered immunity (ETI), and the induction is potentiated by salicylic acid (SA) pretreatment. In addition, Pst actively suppresses PAMP triggered ethylene induction in a type III secretion system-dependent manner. SA potentiation of ethylene induction is dependent mostly on MITOGEN-ACTIVATED PROTEIN KINASE6 (MPK6) and MPK3 and their downstream ACS2 and ACS6, two type I isoforms of 1-aminocyclopropane-1-carboxylic acid synthases (ACSs). ACS7, a type III ACS whose expression is enhanced by SA pretreatment, is also involved. Pst expressing the avrRpt2 effector gene (Pst-avrRpt2), which is capable of triggering ETI, induces a higher level of ethylene production, and the elevated portion is dependent on SALICYLIC ACID INDUCTION DEFICIENT2 and NONEXPRESSER OF PATHOGENESIS-RELATED GENE1, two key players in SA biosynthesis and signaling. High-order ACS mutants with reduced ethylene induction are more susceptible to both Pst and Pst-avrRpt2, demonstrating a positive role of ethylene in plant bacterial resistance mediated by both PAMP-triggered immunity and ETI. PMID- 26265776 TI - A Method of Accounting for Enzyme Costs in Flux Balance Analysis Reveals Alternative Pathways and Metabolite Stores in an Illuminated Arabidopsis Leaf. AB - Flux balance analysis of plant metabolism is an established method for predicting metabolic flux phenotypes and for exploring the way in which the plant metabolic network delivers specific outcomes in different cell types, tissues, and temporal phases. A recurring theme is the need to explore the flexibility of the network in meeting its objectives and, in particular, to establish the extent to which alternative pathways can contribute to achieving specific outcomes. Unfortunately, predictions from conventional flux balance analysis minimize the simultaneous operation of alternative pathways, but by introducing flux-weighting factors to allow for the variable intrinsic cost of supporting each flux, it is possible to activate different pathways in individual simulations and, thus, to explore alternative pathways by averaging thousands of simulations. This new method has been applied to a diel genome-scale model of Arabidopsis (Arabidopsis thaliana) leaf metabolism to explore the flexibility of the network in meeting the metabolic requirements of the leaf in the light. This identified alternative flux modes in the Calvin-Benson cycle revealed the potential for alternative transitory carbon stores in leaves and led to predictions about the light dependent contribution of alternative electron flow pathways and futile cycles in energy rebalancing. Notable features of the analysis include the light-dependent tradeoff between the use of carbohydrates and four-carbon organic acids as transitory storage forms and the way in which multiple pathways for the consumption of ATP and NADPH can contribute to the balancing of the requirements of photosynthetic metabolism with the energy available from photon capture. PMID- 26265777 TI - Genetic and Physical Interaction Studies Reveal Functional Similarities between ALBINO3 and ALBINO4 in Arabidopsis. AB - ALBINO3 (ALB3) is a well-known component of a thylakoid protein-targeting complex that interacts with the chloroplast signal recognition particle (cpSRP) and the cpSRP receptor, chloroplast filamentous temperature-sensitive Y (cpFtsY). Its protein-inserting function has been established mainly for light-harvesting complex proteins, which first interact with the unique chloroplast cpSRP43 component and then are delivered to the ALB3 integrase by a GTP-dependent cpSRP cpFtsY interaction. In Arabidopsis (Arabidopsis thaliana), a subsequently discovered ALB3 homolog, ALB4, has been proposed to be involved not in light harvesting complex protein targeting, but instead in the stabilization of the ATP synthase complex. Here, however, we show that ALB3 and ALB4 share significant functional overlap, and that both proteins are required for the efficient insertion of cytochrome f and potentially other subunits of pigment-bearing protein complexes. Genetic and physical interactions between ALB4 and ALB3, and physical interactions between ALB4 and cpSRP, suggest that the two ALB proteins may engage similar sets of interactors for their specific functions. We propose that ALB4 optimizes the insertion of thylakoid proteins by participating in the ALB3-cpSRP pathway for certain substrates (e.g. cytochrome f and the Rieske protein). Although ALB4 has clearly diverged from ALB3 in relation to the partner recruiting C-terminal domain, our analysis suggests that one putative cpSRP binding motif has not been entirely lost. PMID- 26265778 TI - Inflammatory Markers Related to Microbial Translocation Among HIV-Infected Pregnant Women: A Risk Factor of Preterm Delivery. AB - BACKGROUND: This study was performed to assess the role of lipopolysaccharide modulators as a marker of microbial translocation among human immunodeficiency virus (HIV)-infected women during pregnancy and to evaluate their association with preterm delivery. METHODS: The study had a prospective cohort design and was performed at the Hospital Clinic in Barcelona, Spain. Thirty-six pregnant women with and 36 without HIV infection, matched on the basis of age and parity, were included. Maternal blood samples were obtained during the first trimester, during the third trimester, and at delivery. Levels of soluble CD14 (sCD14), human lipopolysaccharide-binding protein (LBP), immunoglobulin M endotoxin core antibodies to lipopolysaccharide (EndoCAb), and interleukin 6 (IL-6) were determined. Fetal cord blood levels of sCD14, LBP, and IL-6 were determined. Results were compared between groups. RESULTS: First trimester sCD14 and LBP levels and third trimester sCD14 levels were significantly higher in the HIV infected group. HIV-infected women with preterm births and spontaneous preterm births had significantly increased levels of sCD14 throughout pregnancy and significantly increased levels of LBP during the first trimester, compared with HIV-infected women with delivery at term or with HIV-negative women. On multivariate analysis, an independent association was observed between first trimester sCD14 levels and preterm delivery among HIV-infected women. CONCLUSIONS: This is the first study to assess inflammatory markers related to microbial translocation during pregnancy among HIV-infected women. Higher levels of sCD14 and LBP were observed in HIV-infected pregnant women and were associated with preterm delivery. PMID- 26265779 TI - Antiretroviral Therapy and Adverse Pregnancy Outcome: The Elephant in the Room? PMID- 26265780 TI - Antiretroviral Therapy in Relation to Birth Outcomes among HIV-infected Women: A Cohort Study. AB - Although the beneficial effects of antiretroviral (ARV) therapy for preventing mother-to-child transmission are indisputable, studies in developed and developing countries have reported conflicting findings on the association between ARV exposure and adverse birth outcomes. We conducted a prospective observational study at 10 human immunodeficiency virus (HIV) care and treatment centers in Dar es Salaam, Tanzania. Multivariate log-binomial regression was used to investigate the associations between ARV use and adverse birth outcomes among HIV-negative HIV-exposed infants. Our findings demonstrate an increased risk of adverse birth outcomes associated with the use of highly active antiretroviral therapy during pregnancy. Further studies are needed to investigate the underlying mechanisms and identify the safest ARV regimens for use during pregnancy. PMID- 26265782 TI - New editor of the breast section in Acta Radiologica/Acta Radiologica Open. PMID- 26265781 TI - Combined PI3K/Akt and Hsp90 targeting synergistically suppresses essential functions of alloreactive T cells and increases Tregs. AB - Acute graft-versus-host disease is still a major cause of transplant-related mortality after allogeneic stem cell transplantation. It requires immunosuppressive treatments that broadly abrogate T cell responses, including beneficial ones directed against tumor cells or infective pathogens. Inhibition of the heat shock protein of 90 kDa has been demonstrated to eliminate tumor cells, as well as alloreactive T cells while preserving antiviral T cell immunity. Here, we show that the suppressive effects of heat shock protein of 90 kDa inhibition on alloreactive T cells were synergistically enhanced by concomitant inhibition of the PI3K/Akt signaling pathway, which is also strongly activated upon allogeneic stimulation. Molecular analyses revealed that this antiproliferative effect was mainly mediated by induction of cell-cycle arrest and apoptosis. In addition, we observed an increased proportion of activated regulatory T cells, which critically contribute to acute graft-versus-host disease control, upon combined heat shock protein of 90 kDa/Akt isoforms 1 and 2 or heat shock protein of 90 kDa/PI3K/p110delta isoform inhibition. Moreover, antiviral T cell immunity was functionally preserved after combined heat shock protein of 90 kDa/Akt isoforms 1 and 2 inhibition. Taken together, our data suggest that the combined heat shock protein of 90 kDa/PI3K/Akt inhibition approach represents a reasonable dual strategy to suppress residual tumor growth and efficiently deplete alloreactive T cells and thus, provide a rationale to prevent and treat acute graft-versus-host disease selectively without impairing pathogen-specific T cell immunity. PMID- 26265787 TI - Inner Workings: Using the atmosphere as a giant cosmic-ray detector. PMID- 26265789 TI - A retrospective cross-sectional study on the association between tobacco smoking and incidence of ST-segment elevation myocardial infarction and cardiovascular risk factors. AB - BACKGROUND: Cigarette smoking is a well-established risk factor for the development of coronary heart disease. However, the relationship between smoking and acute ST-segment elevation myocardial infarction (STEMI) is less well described. OBJECTIVE: To determine the relative risk of acute STEMI in smokers and ex-smokers, compared with individuals who had never smoked. METHODS: This observational study studied all patients with STEMI undergoing percutaneous coronary intervention (PCI) in South Yorkshire, UK from 1 January 2009 to 6 April 2012. Additional contemporary demographical data for the South Yorkshire population, supplied by the Office for National Statistics, allowed derivation of the incidence rate of STEMI in South Yorkshire-both overall and stratified by smoking status. Incidence rate ratios and population attributable risk (PAR) were calculated to quantify STEMI risk. RESULTS: There were 1715 STEMIs in 1680 patients during the study period. Smoking status was obtained in 96.2% patients. The prevalence of smoking was 47.3% in patients with STEMI and 22.0% in the general population. In patients with STEMI, smokers were ~10 years younger, mean (SD) 57.2 (11.1) years, than never-smokers, 66.4 (12.1) years, and ex-smokers, 67.9 (11.9) years. The age-standardised incident rate ratio of STEMI was 5.2 (4.5 6.1) for current smokers and 1.1 (1.0-1.3) for ex-smokers, with the reference group being never-smokers for both. Almost 50% of STEMIs were attributable to smoking (PAR=48.3%). CONCLUSION: Cigarette smoking is associated with a fivefold increased risk of STEMI. Smoking cessation reduced this risk to a level similar to never-smokers. PMID- 26265790 TI - Digoxin: its role in contemporary medicine. AB - Digoxin has been a key therapeutic for heart failure and atrial tachyarrhythmias for over 200 years following Withering's groundbreaking work depicting the therapeutic benefit of the common botanical foxglove in his 1785 monograph. The use of digoxin preceded any randomised evidence or even basic understanding of its mechanism of action. Over the past two decades, there has been mounting evidence further challenging the safety and efficacy of digoxin, while multiple other therapies for both heart failure and atrial tachyarrhythmias have proven to be more effective and safe. Altogether, digoxin still has an important role in contemporary pharmacotherapeutics, though its role remains controversial and should be reserved for selective patients and clinical situations, with careful attention to serum concentrations. PMID- 26265791 TI - Inflammation-induced microvascular insulin resistance is an early event in diet induced obesity. AB - Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications. PMID- 26265792 TI - Modified high-intensity interval training reduces liver fat and improves cardiac function in non-alcoholic fatty liver disease: a randomized controlled trial. AB - Although lifestyle changes encompassing weight loss and exercise remain the cornerstone of non-alcoholic fatty liver disease (NAFLD) management, the effect of different types of exercise on NAFLD is unknown. This study defines the effect of modified high-intensity interval training (HIIT) on liver fat, cardiac function and metabolic control in adults with NAFLD. Twenty-three patients with NAFLD [age 54+/-10 years, body mass index (BMI) 31+/-4 kg/m(2), intra-hepatic lipid >5%) were assigned to either 12 weeks HIIT or standard care (controls). HIIT involved thrice weekly cycle ergometry for 30-40 min. MRI and spectroscopy were used to assess liver fat, abdominal fat and cardiac structure/function/energetics. Glucose control was assessed by oral glucose tolerance test and body composition by air displacement plethysmography. Relative to control, HIIT decreased liver fat (11+/-5% to 8+/-2% compared with 10+/-4% to 10+/-4% P=0.019), whole-body fat mass (35+/-7 kg to 33+/-8 kg compared with 31+/ 9 kg to 32+/-9 kg, P=0.013), alanine (52+/-29 units/l to 42+/-20 units/l compared with 47+/-22 units/l to 51+/-24 units/l, P=0.016) and aspartate aminotransferase (AST; 36+/-18 units/l to 33+/-15 units/l compared with 31+/-8 units/l to 35+/-8 units/l, P=0.017) and increased early diastolic filling rate (244+/-84 ml/s to 302+/-107 ml/s compared with 255+/-82 ml/s to 251+/-82 ml/s, P=0.018). There were no between groups differences in glucose control. Modified HIIT reduces liver fat and improves body composition alongside benefits to cardiac function in patients with NAFLD and should be considered as part of the broader treatment regimen by clinical care teams. ISRCTN trial ID: ISRCTN78698481. PMID- 26265793 TI - Cerebrospinal Fluid Biomarkers in Spinocerebellar Ataxia: A Pilot Study. AB - Neurodegenerative diseases, including the spinocerebellar ataxias (SCA), would benefit from the identification of reliable biomarkers that could serve as disease subtype-specific and stage-specific indicators for the development and monitoring of treatments. We analyzed the cerebrospinal fluid (CSF) level of tau, alpha-synuclein, DJ-1, and glial fibrillary acidic protein (GFAP), proteins previously associated with neurodegenerative processes, in patients with the autosomal dominant SCA1, SCA2, and SCA6, and the sporadic disease multiple system atrophy, cerebellar type (MSA-C), compared with age-matched controls. We estimated disease severity using the Scale for the Assessment and Rating of Ataxia (SARA). Most proteins measured trended higher in disease versus control group yet did not reach statistical significance. We found the levels of tau in both SCA2 and MSA-C patients were significantly higher than control. We found that alpha-synuclein levels were lower with higher SARA scores in SCA1 and tau levels were higher with greater SARA in MSA-C, although this final correlation did not reach statistical significance after post hoc correction. Additional studies with larger sample sizes are needed to improve the power of these studies and validate the use of CSF biomarkers in SCA and MSA-C. PMID- 26265794 TI - Clinical Applications of Natriuretic Peptides in Assessment of Valvular Heart Disease. AB - Biomarkers such as natriuretic peptides (NPs) have evolving clinical utility beyond the scope of heart failure. The role of NPs in the management of valvular heart disease is a growing area of investigation. NPs have much potential in the assessment of asymptomatic patients with hemodynamically significant valvular lesions who have traditionally been excluded from consideration of surgical intervention. NPs also have a role in the risk stratification of these patients as well as in routine surveillance and monitoring. Together with echocardiographic data and functional status, NPs are being incorporated into the management of valvular heart disease. In this review we examine the evidence for the role of natriuretic peptides in assessment of VHD. PMID- 26265796 TI - Bilateral granular dystrophy: A clinicopathogenetic correlation after alcohol assisted debridement with phototherapeutic keratectomy. PMID- 26265795 TI - Serum GRP78 as a Tumor Marker and Its Prognostic Significance in Non-Small Cell Lung Cancers: A Retrospective Study. AB - INTRODUCTION: Glucose-regulated protein 78 (78 kDa, GRP78), which is also known as immunoglobulin heavy chain binding protein (BIP), is a major chaperone in the endoplasmic reticulum (ER). The expression and clinical significance of GRP78 in the serum of non-small cell lung cancer patients have not yet been clearly described. The aims of the present study were to investigate the expression of GRP78 in the serum of non-small cell lung cancer patients, the relationships with clinicopathological parameters, and the potential implications for survival. PATIENTS AND METHODS: A total of 163 peripheral blood samples from non-small cell lung cancer patients were prospectively collected at the Department of Thoracic Surgery, Fudan University Shanghai Cancer, China. Clinical characteristics data, including age, gender, stage, overall survival (OS) time, and relapse-free survival (RFS) time, were also collected. Serum GRP78 levels were measured using a commercially available ELISA kit. The associations between GRP78 levels and clinicopathological characteristics and survival were examined using Student's t test, Kaplan-Meier, or Cox regression analyses. RESULTS: The mean +/- standard error (SE) value of GRP78 was 326.5 +/- 49.77 pg/mL. This level was significantly lower compared with the level in late-stage non-small cell lung cancer patients (1227 +/- 223.6, p = 0.0001). There were no significant correlations with the clinicopathological parameters. No significant difference was found between high GRP78 expression and low GRP78 expression with regard to RFS (p = 0.1585). However, the OS of patients with higher GRP78 expression was significantly poorer (p = 0.0334). CONCLUSIONS: GRP78 was expressed in non-small cell lung cancer patients and was highly enriched in late-stage lung cancer. GRP78 may have an important role in the carcinogenesis of non-small cell lung cancer and may be a prognostic marker for non-small cell lung cancer. PMID- 26265797 TI - Lateral rectus palsy in a case of dengue fever. PMID- 26265798 TI - Onchocercoma in a United Nations Peacekeeper. PMID- 26265799 TI - A fatal case of staphylococcal toxic shock syndrome. PMID- 26265800 TI - Unusual presentation of mucinous adenocarcinoma in a post fistulectomy case. PMID- 26265801 TI - A rare complication of monochorionic twin pregnancy: Twin-reversed arterial perfusion (TRAP) sequence. PMID- 26265802 TI - An unusual case of axillary lymphadenopathy. PMID- 26265803 TI - Phacomatosis pigmentovascularis with Raynaud's phenomena. PMID- 26265804 TI - Role of multiplex reverse-transcriptase PCR for diagnosis of Acute myelosis in an infant with Down's syndrome. PMID- 26265805 TI - Cranio-thoraco-omphalopagus. PMID- 26265806 TI - Creating natural gingival profiles of missing anterior teeth using ovate pontic. PMID- 26265807 TI - Isolated unilateral IIIrd nerve palsy as the only sign of chronic subdural haematoma. PMID- 26265808 TI - Tumor emboli from intrahepatic cholangiocarcinoma causing obstructive jaundice. PMID- 26265809 TI - A bolt from the blue: Lightning injuries. PMID- 26265810 TI - A rare tumour of pancreas in an incidentally discovered pancreatic lipoma. PMID- 26265811 TI - Two cases of anaphylaxis under anaesthesia with vecuronium. PMID- 26265812 TI - A rare case of leukemic presentation of blastoid variant of mantle cell lymphoma with isolated splenic involvement: Flowcytometric revelation. PMID- 26265813 TI - Masseteric cysticercosis with abscess formation: A diagnostic dilemma. PMID- 26265814 TI - Inverted papilloma of frontal sinus with intracranial extension. PMID- 26265815 TI - Hyperperfusion Syndrome after Carotid Artery Stenting. PMID- 26265816 TI - A case of systemic sarcoidosis with ocular presentation. PMID- 26265817 TI - Rehabilitation of a gunshot wound with dental implants. PMID- 26265818 TI - 'White cerebellar sign' in immediate postpartum period. PMID- 26265819 TI - Cerebellar vermian epidermal cyst. PMID- 26265820 TI - Angiomyxolipoma: Unusual swelling of oral cavity. PMID- 26265821 TI - Sjogren's syndrome presenting as hypokalemic paralysis. PMID- 26265822 TI - Vesicouterine fistula: Youssef's syndrome. PMID- 26265823 TI - Ortner's syndrome: A rare cause in an elderly smoker. PMID- 26265824 TI - Polycystic horseshoe kidney. PMID- 26265825 TI - Inherited Factor X (Stuart-Prower Factor) deficiency and its management. PMID- 26265826 TI - Pachydermoperiostosis - Mimic to acromegaly. PMID- 26265827 TI - Xanthogranulomatous appendicitis: Uncommon histological variant of a common entity. PMID- 26265828 TI - Salivary reservoir denture - A novel approach to battle xerostomia. PMID- 26265829 TI - Mature cystic teratoma of gall bladder - Where do they come from? PMID- 26265830 TI - Snake venom ophthalmia. PMID- 26265831 TI - Giant recurrent lipoma of trunk weighing eight kilograms. PMID- 26265832 TI - Spontaneous intra-abdominal bleed following oral anticoagulant therapy. PMID- 26265833 TI - Toxic anterior segment syndrome - A sequel of uneventful cataract surgery. PMID- 26265834 TI - Arthroscopic removal of intraarticular fracture fragment after fracture dislocation of hip. PMID- 26265835 TI - Fracture penis - Is it really an uncommon entity? PMID- 26265836 TI - Reinfection of Varicella zoster in a vaccinated adult. PMID- 26265837 TI - Benign fibrous histiocytoma of the ethmoids in an infant. PMID- 26265838 TI - An unusual case of acute methotrexate toxicity manifesting as ulcers on psoriatic plaques in an elderly male. PMID- 26265839 TI - Restoration of fractured endodontically treated mandibular first molar using custom made cast post and core. AB - The successful treatment of posterior tooth with substantial damage to the tooth structure not only depends on root canal treatment but also by prompt restoration of lost coronal tooth structure. Endodontically treated teeth undergo loss of tooth substance due to dental caries, endodontic therapy or previous restoration and changes in physical characteristics, such as a reduced modulus of elasticity, which often leads to increased fracture susceptibility when compared to unrestored vital teeth.(1) Restoration of endodontically treated posterior teeth is more challenging because of their additional functional requirements. The restorative treatment of such teeth includes the decision of whether or not a post should be used. Post is a dental material placed in the root of structurally insufficient tooth when additional retention is needed to retain the core and coronal restoration.(2,3) However, preparation of a post space adds a certain degree of risk to restorative procedure like perforations and root fracture, especially if an over sized post channel is prepared. PMID- 26265840 TI - A case of transfusion related acute lung injury in a thalassemic child. PMID- 26265841 TI - Takayasu arteritis in pregnancy. PMID- 26265842 TI - Subcortical cysts in anterior temporal regions: Unusual imaging finding in congenital cytomegalovirus infection. PMID- 26265843 TI - Fatal massive hemoptysis: An autopsy study. PMID- 26265844 TI - A common but underreported entity of papulonecrotic tuberculid. PMID- 26265845 TI - Filariasis of the breast. PMID- 26265846 TI - Endovascular management of giant coronary artery aneurysm. PMID- 26265847 TI - Reticulate acropigmentation of Kitamura: A familial case with eyelid involvement. PMID- 26265848 TI - Prosthetic rehabilitation of a serving soldier with custom made ocular prosthesis. PMID- 26265849 TI - Immune reconstitution inflammatory syndrome. PMID- 26265850 TI - A case of familial hypercholesterolaemia Type IIa presenting with tuberous xanthomas. PMID- 26265851 TI - A rare case of idiopathic retinal vasculitis, aneurysms and neuroretinitis (IRVAN) syndrome. PMID- 26265852 TI - Bilateral sterile perforated corneal ulcer in an HIV case. PMID- 26265853 TI - Renal artery injury in paediatric blunt abdominal trauma. PMID- 26265854 TI - Open dislocation of fourth and fifth carpometacarpal joint - An easily missed injury. PMID- 26265855 TI - Frosted branch angiitis in a pregnant woman. PMID- 26265856 TI - Adult T cell large granular lymphocytic leukemia. PMID- 26265857 TI - Optical coherence tomography in the management of posterior scleritis. PMID- 26265858 TI - Severe anaphylactic reaction to diclofenac. PMID- 26265859 TI - Myxofibroma of the soft tissue of face. PMID- 26265860 TI - Interesting case of severe anterior uveitis caused by brimonidine eye drops. PMID- 26265861 TI - Anesthetic management of congenital lobar emphysema in a neonate. PMID- 26265862 TI - Rehabilitation of a case of partial rhinectomy with silicone nasal prosthesis. PMID- 26265863 TI - Post traumatic neovascularisation of a cataractous crystalline lens. PMID- 26265864 TI - A rare case of chronic idiopathic spinal epidural haematoma. PMID- 26265865 TI - Ethylene glycol poisoning. PMID- 26265866 TI - Cerebral sinovenous thrombosis in a child with homocystinuria. PMID- 26265867 TI - Conjunctival limbal autograft transplantation in pterygium surgery by natural haemostasis. PMID- 26265868 TI - Emergency surgical management of double penile fracture at a peripheral hospital. PMID- 26265869 TI - A rare case of intra-pericardial teratoma presenting as a mediastinal mass in an infant. PMID- 26265870 TI - Solid pseudopapillary neoplasm of the pancreas mimicking a pseudocyst of pancreas. PMID- 26265871 TI - A case of 'de novo' Histoid Hansen's disease. PMID- 26265872 TI - Hypercortisolism induced atypical central serous chorioretinopathy in pregnancy. PMID- 26265873 TI - An unusual case of human paragonimiasis. PMID- 26265874 TI - Interdisciplinary management of gingival recession associated with traumatic anterior malocclusion with orthodontics and periodontal plastic surgery. PMID- 26265875 TI - Pulse contour analysis guided management of a case of puerperal uterine inversion and hemorrhagic shock - 'Giving what it takes'. PMID- 26265876 TI - An interesting case of implantable contact lens. PMID- 26265877 TI - Spontaneous heterotopic pregnancy with tubal rupture and pregnancy progressing to term. PMID- 26265878 TI - Coexistence of filariasis with carcinoma breast - An incidental cytological finding. PMID- 26265879 TI - Catheter ablation of an elusive accessory pathway in Ebstein's anomaly - Innovative surrogate for electroanatomic mapping. PMID- 26265880 TI - Giant intra-articular extrasynovial osteochondroma of the Hoffa's fat pad. PMID- 26265881 TI - An uncommon case of primary iris cyst managed with Nd YAG laser. PMID- 26265882 TI - Spontaneous pneumomediastinum. PMID- 26265883 TI - Becker's nevus syndrome. PMID- 26265884 TI - Aspergilloma in a pre-existing unoperated pulmonary echinococcosis. PMID- 26265885 TI - Tonsillolith: A polymicrobial biofilm. PMID- 26265886 TI - Extrapyramidal symptoms after Fluoxetine. PMID- 26265887 TI - Referral Practices for Cognitive Behavioral Therapy for Insomnia: A Survey Study. AB - This study examined referring practices for cognitive behavioral therapy for insomnia (CBTI) by physicians at University of Michigan Hospitals and Weill Cornell Medical College of Cornell University. A five-item questionnaire was sent via email that inquired about the physician's patient load, number of patients complaining of insomnia, percent referred for CBTI, and impressions of what is the most effective method for improving sleep quality in their patients with insomnia. The questionnaire was completed by 239 physicians. More physicians believed a treatment other than CBTI and/or medication was most effective (N = 83). "Sleep hygiene" was recommended by a third of the sample. The smallest number of physicians felt that CBTI alone was the most effective treatment (N = 22). Additional physician education is needed. PMID- 26265888 TI - miR-106a Is Downregulated in Peripheral Blood Mononuclear Cells of Chronic Hepatitis B and Associated with Enhanced Levels of Interleukin-8. AB - AIMS: This study aimed to investigate miR-106a expression in peripheral blood mononuclear cells (PBMCs) of chronic hepatitis B (CHB) patients and to analyze the function of miR-106a. MATERIALS AND METHODS: miR-106a expression levels in PBMCs from 40 healthy controls and 56 CHB patients were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The luciferase activity assays were used to determine whether miR-106a binds to 3'UTR of IL-8. miR-106a mimics and inhibitors were transfected into healthy PBMCs. IL-8 mRNA and protein levels were detected and determined by qRT-PCR and ELISA, respectively. RESULTS: The qRT PCR results suggested that the PBMC miR-106a levels were decreased in CHB patients. IL-8 was augmented in CHB patients and was inversely correlated with miR-106a levels. The luciferase activity assays indicated that IL-8 is a target of miR-106a. Exogenous expression of miR-106a could significantly repress IL-8 expression at both mRNA and protein levels in PBMCs, whereas miR-106a inhibitor had the opposite effects. CONCLUSIONS: This study suggested that miR-106a is downregulated in PBMCs of CHB patients and that miR-106a may play an important role in CHB by targeting IL-8. PMID- 26265889 TI - Expression of Prostacyclin-Synthase in Human Breast Cancer: Negative Prognostic Factor and Protection against Cell Death In Vitro. AB - Endogenously formed prostacyclin (PGI2) and synthetic PGI2 analogues have recently been shown to regulate cell survival in various cell lines. To elucidate the significance of PGI2 in human breast cancer, we performed immunohistochemistry to analyze expression of prostacyclin-synthase (PGIS) in 248 human breast cancer specimens obtained from surgical pathology files. We examined patients' 10-year survival retrospectively by sending a questionnaire to their general practitioners and performed univariate analysis to determine whether PGIS expression correlated with patient survival. Lastly, the effects of PGI2 and its analogues on cell death were examined in a human breast cancer cell line (MCF-7) and a human T-cell leukemia cell line (CCRF-CEM). PGIS expression was observed in tumor cells in 48.7% of samples and was associated with a statistically significant reduction in 10-year survival (P = 0.038; n = 193). Transient transfection of PGIS into MCF-7 cells exposed to sulindac increased cell viability by 50% and exposure to carbaprostacyclin protected against sulindac sulfone induced apoptosis in CCRF-CEM cells. Expression of PGIS is correlated with a reduced patient survival and protects against cell death in vitro, suggesting that PGIS is a potential therapeutic target in breast cancer. PMID- 26265890 TI - Hemolytic uremic syndrome. AB - Hemolytic uremic syndrome (HUS) is a clinical syndrome characterized by the triad of thrombotic microangiopathy, thrombocytopenia, and acute kidney injury. Hemolytic uremic syndrome represents a heterogeneous group of disorders with variable etiologies that result in differences in presentation, management and outcome. In recent years, better understanding of the HUS, especially those due to genetic mutations in the alternative complement pathway have provided an update on the terminology, classification, and treatment of the disease. This review will provide the updated classification of the disease and the current diagnostic and therapeutic approaches on the complement-mediated HUS in addition to STEC-HUS which is the most common cause of the HUS in childhood. PMID- 26265891 TI - Mothers' views of milk banking: sample of Izmir. AB - AIM: The studies on human milk banking in Turkey, has being carried out at a hospital in Izmir province. There are different point of views about milk banking. The aim of the study is to determine the knowledge and the views of the mothers towards milk banking. MATERIAL AND METHODS: This study is a cross sectional survey. The study was carried out with 404 mothers who gave birth in a two maternity hospitals and one university hospital in Izmir using the face-to face interview technique between March 2014 and June 2014. The study data were collected using a 30-item socio-demographic questionnaire. RESULTS: The mothers' mean age was 28.4 years (16-46 years). Of the mothers, 45.5% were primary school graduates, 80.2% were members of a nuclear family, 75.7% had less than three children, 63.4% gave birth by caesarean section and only 79.5 percent were able to breastfeed before being discharged. Of the mothers, 41.6% were aware of milk banking, 71.3% were willing to receive milk bank services and 68.8% were willing to donate breastmilk. 62.2% of those who did not want to make donation stated risk of contagion as a reason, 8.2% of the participants had worked as wet-nurse before. CONCLUSIONS: Most mothers revealed positive approaches and opinions about establishment of milk banking and milk donation. However, there were some concerns due to the risk of infectious diseases and religious beliefs. Efforts should be made to raise awareness and mothers should be informed about the importance of breast milk and breastfeeding so that milk banks can be regarded as an additional choice. PMID- 26265892 TI - The role of tissue harmonic imaging ultrasound combined with power Doppler ultrasound in the diagnosis of childhood febrile urinary tract infections. AB - AIM: This study assessed the ability of tissue harmonic imaging ultrasound combined with power Doppler ultrasound in the detection of childhood febrile urinary tract infections in comparison with the gold standard reference method: Tc-99m dimercaptosuccinicacid renal cortical scintigraphy. MATERIAL AND METHODS: This prospective study included 60 patients who were hospitalized with a first episode of febrile urinary tract infections. All children were examined with dimercaptosuccinicacid scan and tissue harmonic imaging ultrasound combined with power Doppler ultrasound within the first 3 days of admission. RESULTS: Signs indicative of acute infection were observed in 29 patients according to the results of tissue harmonic imaging ultrasound combined with power Doppler ultrasound while dimercaptosuccinicacid scan revealed abnormal findings in 33 patients. The sensitivity, specificity, positive predictive value and negative predictive value of tissue harmonic imaging combined with power Doppler ultrasound using dimercaptosuccinicacid scintigraphy as the reference method in patients diagnosed with first episode febrile urinary tract infections were calculated as 57.58% (95% confidence interval: 40.81%-72.76%); 62.96% (95% confidence interval: 44.23%-78.47%); 65.52% (95% confidence interval: 52.04% 77%); 54.84% (95% confidence interval: 41.54%-67.52%); respectively. CONCLUSIONS: Although current results exhibit inadequate success of power Doppler ultrasound, this practical and radiation-free method may soon be comprise a part of the routine ultrasonographic evaluation of febrile urinary tract infections of childhood if patients are evaluated early and under appropriate sedation. PMID- 26265893 TI - Diagnostic evaluation of our patients with hemophilia A: 17-year experience. AB - AIM: Hemophilia A is a rare inherited bleeding disorder resulting from factor VIII deficiency and is a group of diseases characterized by intra-articular and intramuscular bleeding. In this study, we aimed to retrospectively evaluate the treatment outcomes, demographic and clinical characteristics of our patients who were treated and followed up for last 17 years in our pediatric hematology unit with a diagnosis of Hemophilia A. MATERIAL AND METHODS: The medical records of 83 patients who were diagnosed with Hemophilia A and followed up between 1997 and 2014 in our hospital's pediatric hematology clinic were reviewed retrospectively. The demographic data, prophylaxis state, development of inhibitors and clinical characteristics of the patients were evaluated. RESULTS: When the complaints at presentation were examined, it was found that 27 (32%) patients had hemarthrosis, 24 (29%) patients had ecchymosis and hematoma, 13 (16%) patients had prolonged bleeding after trauma or cut, 10 (12%) patients had gingival, mouth or nose bleeding, 4 (5%) patients had prolonged bleeding after circumcision, 4 (5%) patients had gastrointestinal bleeding, 1 (1%) patient had hematuria. Fifty (60%) patients were considered severe hemophilia A, 20 (24%) patients were considered moderate hemophilia A and 13 (16%) patients were considered mild hemophilia A according to factor activity. Among severe hemophilia A patients, primary prophylaxis was being administered in 2 (2%) patients and secondary prophylaxis was being administered in 40 (48%) patients. Inhibitor positivity was found in 8 (10%) of these patients. It is found that hemophilic artropathy developed in 17 patients and 8 of these 17 patients had undergone radioisotope synovectomy. CONCLUSIONS: Treatment of severe bleeding in hemophilia A patients should be performed in hospital and the presence of inhibitor must be investigated in cases of uncontrolled bleeding where adequate doses of factor concentrates have been administered for treatment. In order to decrease the development of inhibitor, prophlaxis should be suggested to patients rather than repetetive treatment when bleeding occurs. The radioactive synovectomy should not be overlooked in countries like ours in which factors can not be used adequately. PMID- 26265894 TI - Evaluation of blood cultures in a children's hospital located in Southeastern Anatolia. AB - AIM: Bloodstream infections in hospitalized patients are one of the most important causes of morbidity and mortality despite antimicrobial therapy. Early diagnosis and treatment of these infections is crucial. The aim of this study was to evaluate the distribution and antibiotic susceptibility of bacteria isolated from blood cultures in a children's hospital in the Southeastern Anatolia during an 18-month period. MATERIAL AND METHODS: 7 040 blood cultures which were sent from hospitalized patients in Gaziantep Children's Hospital between 01.07.2010 and 01.01.2012 were evaluated. RESULTS: A total of 7 040 blood cultures were evaluated in this study. Microbial growth was detected in 2075 (29.47%) blood cultures. The most frequently isolated bacteria were coagulase-negative staphylococci (%45.97) which were followed by Salmonella spp. (%7.8). 12.12% of enterococcal isolates were resistant to glycopeptide antibiotics. The most frequently isolated gram negative bacterium was Salmonella spp. 15.43% of Salmonella spp. showed decreased susceptibility against quinolones. The ESBL positivity rate of E. coli and K. pneumoniae strains was found to be 35.08% and 57.14%, respectively. The imipenem resistance rate of P. aeruginosa was found to be 33.33%. The most common nonfermentative bacterium was S. maltophilia. CONCLUSIONS: The distribution of bacteria isolated from blood cultures and antibiotic resistance rates differ among different regions of Turkey. Different results obtained in our study may be related with regional tendencies to infections and patient population. Distribution of infectious agents and antibiotic resistance rates should be evaluated at regular intervals. This will lead to establishment of proper antibiotic usage policies in our country. PMID- 26265895 TI - Childhood mastocytosis: results of a single center. AB - AIM: We aimed to retrospectively evaluate histopathological, demographic and clinical findings of children with mastocytosis diagnosed with mastocytosis in our clinic. MATERIAL AND METHODS: The files of 21 patients diagnosed with mastocytosis between 2000 and 2014 in our clinic were retrospectively analyzed. RESULTS: All patients had cutaneous mastocytosis, 19 patients had urticaria pigmentosa and 2 patients had mastocytoma. The male-female ratio was: 1/1.6. The median age for onset of disease was 12.1 months and the disease occured in the newborn period in 3 patients. While all patients had eruption, 10 patients had pruritis, 1 patient had a bullous formation, 1 patient had abdominal pain and 1 patient had attacks of redness throughout the body and a sense of burning in the chest. Two patients had a positive familial history. The diagnosis was confirmed with skin biopsy in all patients. The median follow up time of the patients were 5 years. The patients were treated with H1, H2 antihistaminics, local moisturizing creams and topical corticosteroid drugs. The lesions resolved completely in 4 patients who reached to puberty and 7 patients had marked improvement in a 5.5 year-follow-up period. Ten patients had stabile lesions in a 3.6 year-follow-up period. CONCLUSIONS: Most cases of childhood mastocytosis are observed in the form of cutaneous mastocytosis. The prognosis is good; the disease limits itself and is prone to regress in the adolescent period. PMID- 26265896 TI - McCune Albright syndrome in association with excessive GH secretion: case report. AB - McCune-Albright Syndrome is a rare syndrome characterized with excessive function of peripheral endocrine organs and activating mutations of the stimulatory G protein alpha subunit are involved in the pathogenesis. The three main findings of the disease include hyperpigmented cafe au lait spots, fibrous dysplasia and increased endocrine functions and excessive secretion of growth hormone is observed in 21% of the patients. Clinical signs may be missed in these patients because of precocious puberty and craniofacial fibrous dysplasia. Since radiotherapy causes to sarcomatous changes and transsphenoidal surgery may cause to severe thickening in the cranial bones, they are not appropriate treatment options and medical treatment is recommended. Bromocriptine, cabergoline and octreotide or different combinations of these drugs are used in treatment and pegvisomant has also been used in recent years. Here, we present a male patient aged 12 years and 7 months to show gigantism as a rare clinical reflection of McCune-Albright Syndrome with an excessive height (197 cm), cafe au lait spots, growht hormone levels which could not be supressed with oral glucose tolerance test and increased prolactin levels. PMID- 26265897 TI - A case of neonatal arterial thrombosis mimicking interrupted aortic arch. AB - Neonatal arterial thrombosis is a very rare entity with clinical findings resembling coarctation of aorta or interrupted aortic arch. A two day-old male newborn was admitted to a different hospital with difficulty in sucking and sleepiness. On echocardiographic examination, a diagnosis of interrupted aortic arch was made and he was treated with prostoglandin E2. When the patient presented to our center, physical examination revealed that his feet were bilaterally cold. The pulses were not palpable and there were ecchymotic regions in the lower extremities. Echocardiography ruled out interrupted aortic arch. Computerized tomographic angiography revealed a large thrombosis and total occlusion of the abdominal aorta. Since there was no response to treatment with tissue plasminogen activator, we performed thrombectomy. Homozygous Factor V Leiden and Methylenetetrahydrofolate reductase mutations were found in this patient. Neonatal aortic thrombosis which is observed very rarely and fatal should be considered in the differential diagnosis of coarctation of aorta and interrupted aortic arch. PMID- 26265898 TI - Kluyvera ascorbata infections in children: a case series. AB - Kluyvera is a relatively newly described member of the Enterobacteriaceae family that rarely causes infections in humans. In the pediatric population, it is described in association with clinically significant infections ranging from urinary tract infections to sepsis with multiorgan failure. Our aim is to determine the clinical significance of K. ascorbata infections in the pediatric population at our institution. We retrospectively analyzed clinical microbiology data as from 2006 and identified four clinically significant isolates in this period. The isolates were from four cases who presented with sepsis, bacteremia associated with central venous catheter, pyelonephritis and intraabdominal collection. The ages of these patients ranged between seven months to 17 years. All patients received prompt antimicrobial treatment on the basis of susceptibility testing and good clinical response was obtained in all patients. Successful treatment options include third-generation cephalosporins, aminoglycosides, betalactams with beta-lactamase inhibitors and carbapenems. Clinicians should be aware of the spectrum of disease and increasing clinical importance associated with this pathogen. PMID- 26265899 TI - A rare case of cardiac anomaly: prenatally diagnosed ectopia cordis. AB - Ectopia cordis is a rare congenital malformation in which the heart is located partially or totally outside the thoracic cavity. The estimated prevalence of ectopia cordis is 5.5-7.9 per million births and it comprises 0.1% of congenital heart diseases. Ectopia cordis is associated with other congenital heart diseases and various tissue and organ disorders. Common cardiac anomalies associated with ectopia cordis include ventricular septal defect, atrial septal defect, pulmonary stenosis, right ventricular diverticulum, double right ventricular outflow tract and tetralogy of Fallot. Extracardiac anomalies associated with ectopia cordis reported in the literature include omphalocele, gastrochisis, cleft lip and palate, scollosis and central nervous system malformations. Here we report a newborn with ectopia cordis who was diagnosed prenatally. PMID- 26265900 TI - Two important factors affecting the transition to breastfeeding in preterm infants: corrected age and periventricular leukomalacia. PMID- 26265901 TI - Validation of three pain scales among adult postoperative patients in Ghana. AB - BACKGROUND: Pain assessment is an important component of pain management and health professionals require valid tools to assess pain to guide their pain management decisions. The study sought to select, develop, and validate context appropriate unidimensional pain scales for pain assessment among adult post operative patients. METHODS: A mixed methods design was adopted. The study was conducted at two hospitals in Accra, Ghana. The qualitative phase involved 17 patients and 25 nurses, and the quantitative phase involved 150 post-operative patients. Qualitative data was collected iteratively through individual interviews and focus groups. RESULTS: Two existing pain scales (0-10 Numeric Rating Scale [NRS] and Wong-Baker FACES [FPS] scales) and one new pain scale (Colour-Circle Pain Scale-[CCPS]) were validated. The psychometric properties of the three scales were assessed when patients had fully recovered from anesthesia. The CCPS had higher scale preference than NRS and FPS. Convergent validity was very good and significant (0.70-0.75). Inter-rater reliability was high (0.923 0.928) and all the scales were sensitive to change in the intensity or level of pain experienced before and after analgesia such as paracetamol and diclofenac suppositories, injectable pethidine, and oral tramadol had been administered. CONCLUSION: Using a valid tool for pain assessment gives the clinician an objective criterion for pain management. Due to the subjective nature of pain, consideration of socio-cultural factors for the particular context ensures that the appropriate tool is used. PMID- 26265902 TI - No difference in hypertension prevalence in smokers, former smokers and non smokers after adjusting for body mass index and age: a cross-sectional study from the Czech Republic, 2010. AB - BACKGROUND: Several hypotheses suggest a temporary increase in blood pressure following smoking cessation. This may be the result of endocrine changes (e.g. alteration in adrenocorticotropic hormone and cortisol levels in post-cessation period) and/or post-cessation weight gain. Our aim was to identify factors that may be associated with the diagnosis of hypertension after quitting smoking. METHODS: In 2010, we conducted a cross-sectional survey in a sample of 2065 Czech adults, chosen by quota selection and representative according to age, gender, education, region of residence and the size of settlement, aged 18 to 94 years. We examined the association between age, gender, body mass index, smoking status, and education with the hypertension diagnosis in their personal history. Data were compiled and weighed by age categories. Statistical significance was measured by Pearson Chi-square test at the level of significance 95 %. RESULTS: Diagnosis of hypertension was reported in 461 (22 %) subjects, with no difference by gender. Based on univariate analysis, former smokers were more likely than non smokers to be diagnosed for hypertension (OR 1.450 (1.110-1.900), p = 0.006). However, after adjusting for body mass index and age, the occurrence of hypertension diagnosis did not differ among non-smokers, smokers and former smokers (OR 0.760 for smokers, p = 0.082 and OR 1.020 for former smokers, p = 0.915). CONCLUSION: We did not find any differences in hypertension diagnosis prevalence according to smoking status. PMID- 26265903 TI - Neuro-Behcet: Pons Involvement with Longitudinal Extension to Midbrain and Hypertrophic Olivary Degeneration. AB - A 21-year-old right-handed man developed progressive dysarthria and gait disturbance over 4 months (associated with intermittent hiccups). During that time, he also suffered from uveitis. A physical examination showed pseudobulbar and pyramidal signs and genital and oral ulcers. A brain MRI revealed an extensive lesion mainly located in the ventral pons, with an extension upwards to the midbrain. The inferior olivary nucleus also showed hyperintensity. After the treatment with intravenous methylprednisolone and pulses of cyclophosphamide, he improved. As observed on his MRI, his lesions also improved, except for an increase of the inferior olivary nucleus, consistent with hypertrophic olivary degeneration. Neuro-Behcet tropism for ventral brainstem explains the usual presentation with pyramidal syndrome. Hypertrophic olivary degeneration due to pons involvement could explain the hiccup attacks in a few known cases. PMID- 26265904 TI - Corneal Hydrops in Pellucid Marginal Degeneration: A Case Series. AB - PURPOSE: To report an unusual presentation of pellucid marginal degeneration (PMD) and its management by using air injection and tension sutures. CASE REPORT: We report 2 cases with a history of acute pain and loss of vision. Examination revealed hydrops at the 6-9 o'clock meridian with Descemet's membrane detachment and tear at the same area and advanced PMD in the other eye. DISCUSSION: Air injection with suturing to treat the hydrops in PMD and crescentic excision with lamellar grafting instead of lamellar keratoplasty lead to better results than conservative management. CONCLUSION: Corneal hydrops and perforation in patients with PMD is a rare presentation and can be managed by tension sutures and air injection. PMID- 26265905 TI - A Case of Coats' Disease with Spontaneous Retinal Reattachment after Total Detachment. AB - PURPOSE: To report a case of Coats' disease in which spontaneous reattachment occurred after total retinal detachment. PATIENT AND METHODS: A young boy (patient age: 4 years and 11 months) presented with leukocoria in the left eye. Slit-lamp examination revealed total retinal detachment with abnormal retinal blood vessels and subretinal exudation just behind the lens. Computed tomography imaging showed no solid mass lesion in the intraocular space. Secondary total retinal detachment as a complication of Coats' disease was diagnosed. No light perception was detected, so we determined that surgical treatment was not indicated. RESULTS: Four months after the initial diagnosis, the retina showed complete reattachment with a large amount of subretinal hard exudate. Visual acuity remained unchanged, with no light perception. CONCLUSIONS: We speculate that the spontaneous retinal reattachment in the present case was caused by the decreased permeability of the abnormal retinal vessels and the good functional effect of the retinal pigment epithelium. PMID- 26265906 TI - Complete Visual Rehabilitation in a Patient with No Light Perception after Surgical Management of a Penetrating Open-Globe Injury: A Case Report. AB - Open-globe injuries with no light perception (NLP) carry a poor prognosis, and many ophthalmologists select a primary enucleation or evisceration as a result. We present a case of complete visual rehabilitation in a patient who presented with NLP after a zone III penetrating open-globe injury. We recommend patient counseling regarding decision making and management of ocular trauma with NLP, since timely intervention and close follow-ups may restore useful or complete vision even in severely traumatized eyes. PMID- 26265907 TI - Optical Coherence Tomography in an Infant with Walker-Warburg Syndrome. AB - PURPOSE: Walker-Warburg syndrome (WWS) is a type of congenital muscular dystrophy (CMD) characterised by severe brain malformation, lissencephaly, and congenital eye abnormalities. Despite the coexistence of various eye abnormalities, results from optical coherence tomography (OCT) in WWS have not previously been reported. We herein report specific OCT findings in an infant with WWS. PATIENTS AND METHODS: The patient was a 14-day-old boy delivered by caesarean section at 38 weeks and 4 days of gestation and with a birth weight of 2,543 g. A cranial MRI showed lissencephaly, hydrocephalus, an encephalocele, and cerebellar hypoplasia, consistent with the diagnosis of WWS. RESULTS: A bilateral ocular examination showed no abnormalities of the anterior eye segment. A fundus examination showed a persistent hyaloid artery in the vitreous cavity, a widespread loss of fundus pigmentation, transparent choroidal vessels (some choroidal vessel sections were visible), and the absence of a distinct macular reflex. OCT showed no foveal pit and an indistinct laminar structure of the retina. The infant subsequently developed congenital glaucoma and he then died of respiratory failure at the age of 8 months. CONCLUSIONS: WWS is associated with a high incidence of congenital eye abnormalities, and this infant showed findings consistent with WWS. OCT revealed a marked retinal dysplasia. PMID- 26265908 TI - Intraoperative Optical Coherence Tomography-Assisted 27-Gauge Vitrectomy in Eyes with Vitreoretinal Diseases. AB - OBJECTIVE: To report intraoperative optical coherence tomography (iOCT)-assisted 27-gauge microincision vitrectomy surgery (MIVS) in eyes with vitreoretinal disease. METHODS: A retrospective, interventional case series performed at a single center, including 6 eyes with retinal disease that underwent iOCT-assisted 27-gauge MIVS. RESULTS: The advantages of iOCT were most notable when it was used to evaluate, in real time, different macular areas: the pre-macula, in vitreomacular traction or epiretinal membrane; the intra-macula, in macular edema or macular hole; and the sub-macula, in macular detachment. Real-time imaging and the minimization of shadows cast on the underlying tissues by the 27-gauge instrumentation made it possible to quickly select the best procedure at each critical juncture of the surgery. No patients experienced any complications. CONCLUSION: Real-time iOCT imaging during 27-gauge MIVS provided excellent intraoperative visualization of retinal tissues without causing significant obstructions to the surgeon. The positive feedback from the system allowed the surgeon to better judge the necessity of additional surgical procedures. PMID- 26265909 TI - Postsurgical Cystoid Macular Edema following Posterior Chamber Toric Phakic Intraocular Lens Implantation Surgery: A Case Report. AB - PURPOSE: To describe a case of cystoid macular edema (CME) developing after posterior chamber toric phakic intraocular lens (PIOL) implantation. METHODS: Case report. RESULTS: A 33-year-old male underwent implantation of toric implantable collamer lenses (ICL), a new generation of PIOLs, for both eyes. Preoperative best spectacle-corrected distance visual acuity (BCVA) was 20/25 in the right eye and 20/32 in the left eye, with a manifest refraction of -9.25 -4.0 * 4 degrees and -9.75 -4.25 * 171 degrees , respectively. On day 1 postoperatively, the left eye had an uncorrected distance visual acuity (UDVA) of 20/60 with a refraction of +2.0 -3.5 * 11 degrees . Despite the rotation of the PIOL, the cylindrical refractive component persisted in the left eye with a refraction of +2.0 -3.5 * 11 degrees . Two weeks after the initial surgery, he presented with a decrease in his visual acuity in the left eye. The UDVA and BCVA were both 20/100 in the left eye with a refraction of +2.0 -4.25 * 3 degrees . Dilated fundus examination and macular optical coherence tomography revealed a CME in the left eye. Following topical nepafenac therapy and explantation of the ICL, we observed a complete resolution of the CME at 3 months with an improvement in BCVA to 20/32 in the left eye. CONCLUSIONS: To our knowledge, this is the first reported case of postsurgical CME following toric ICL implantation. In cases of phakic eyes with an intact posterior capsule, postsurgical CME can develop, thus highlighting the purpose of this report. PMID- 26265910 TI - Short Door-to-Needle Times in Acute Ischemic Stroke and Prospective Identification of Its Delaying Factors. AB - BACKGROUND: The clinical benefit of intravenous thrombolysis (IVT) in acute ischemic stroke is time dependent. Several studies report a short median door-to needle time (DNT; 20 min), mainly in large tertiary referral hospitals equipped with a level 1 emergency department, a dedicated stroke team available 24/7, and on-site neuroimaging facilities. Meanwhile, in daily practice, the majority of stroke patients are admitted to secondary care hospitals, and in practice, even the generous benchmark of the American Heart Association (a DNT of 60 min in >80% of the cases) is met for a minority of patients treated with IVT. The first objective of our study was to investigate if, in a secondary care teaching hospital rather than a tertiary referral hospital, similar short DNTs can be accomplished with an optimized IVT protocol. Our second objective was to prospectively identify factors that delay the DNT in this setting. METHODS: A multicenter, consecutive cohort study of patients treated with IVT in one of two secondary care teaching hospitals. In both hospitals, data of consecutive stroke patients as well as median DNTs and factors delaying this were prospectively assessed for each patient. Multivariable logistic regression analysis was used to evaluate associations between patient-related and logistic factors with a delayed (i.e. exceeding 30 min) DNT. RESULTS: In total, 1,756 patients were admitted for ischemic stroke during the study period. Out of these, 334 (19.0%) patients were treated with IVT. The median DNT was 25 min (interquartile range: 20-35). A total of 71% (n = 238) had a DNT below 30 min. In 63% of the patients treated with IVT the DNT was delayed by at least one factor. Patients without any delaying factor had a 10 min shorter median DNT compared to patients with at least one delaying factor (p < 0.001). The following factors were independently associated with a delayed DNT: uncertainty about symptom onset, uncontrolled blood pressure, fluctuating neurological deficit, other treatment before IVT, uncertainty about (anti-)coagulation status, other patient-related factors, and incorrect triage. CONCLUSIONS: Short median DNTs can also be accomplished in secondary care. Despite the short DNTs, several delaying factors were identified that could direct future improvement measures. This study supports the view that as a performance measure, the current DNT targets are no longer ambitious enough and it adds to the knowledge of factors delaying the DNT. PMID- 26265911 TI - Clinical Characteristics of Transient Ischemic Attack Patients with Atrial Fibrillation: Analyses of a Multicenter Retrospective Study. AB - BACKGROUND: Atrial fibrillation (AF) is an important risk factor for transient ischemic attack (TIA). However, little is known about the characteristics of TIA patients with AF. This study investigated the characteristics of such patients, using data from a retrospective, observational, multicenter study. METHODS: TIA patients admitted to 13 stroke centers in Japan within 7 days of onset between January 2008 and December 2009 were included. The present analyses compared baseline characteristics, clinical symptoms, findings from diffusion-weighted imaging (DWI), and clinical outcomes between patients with and without AF (AF and non-AF groups). RESULTS: A total of 464 patients (292 men; mean age 68.5 +/- 13.2 years) were registered. Of these, 79 patients (17%) had AF. Patients in the AF group were older (73.9 +/- 9.1 vs. 67.4 +/- 13.6 years, p < 0.001) and more likely to show disturbance of consciousness (13 vs. 6%, p = 0.046) and aphasia (9 vs. 3%, p = 0.007) than patients in the non-AF group. Although no difference in the overall DWI-positive rate was seen between the groups (28 vs. 20%, p = 0.102), a single lesion (23 vs. 10%, p < 0.001), a lesion >=15 mm (11 vs. 4%, p = 0.006), and a single lesion >=15 mm (11 vs. 2%, p < 0.001) on DWI were more frequent in the AF group. Multivariate logistic regression analysis identified increased age [odds ratio (OR) 1.04; 95% confidence interval (CI) 1.02-1.07] and DWI single lesion >=15 mm (OR 5.67; 95% CI 1.92-16.7) as independently associated with the presence of AF. CONCLUSIONS: In this study, 17% of our TIA patients had AF. We found an association between the acute ischemic lesion pattern on DWI of a single lesion >=15 mm and AF in TIA patients. These results might lead to a better diagnosis of TIA patients with AF. PMID- 26265912 TI - Effect of the Interindividual Variability on Computational Modeling of Transcranial Direct Current Stimulation. AB - Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low intensity, direct current to cortical areas facilitating or inhibiting spontaneous neuronal activity. This paper investigates how normal variations in anatomy may affect the current flow through the brain. This was done by applying electromagnetic computational methods to human models of different age and gender and by comparing the electric field and current density amplitude distributions within the tissues. Results of this study showed that the general trend of the spatial distributions of the field amplitude shares some gross characteristics among the different human models for the same electrode montages. However, the physical dimension of the subject and his/her morphological and anatomical characteristics somehow influence the detailed field distributions such as the field values. PMID- 26265913 TI - Impact of a Virtual Clinic in a Paediatric Cardiology Network on Northeast Brazil. AB - Introduction. Congenital heart diseases (CHD) affect approximately 1% of live births and is an important cause of neonatal morbidity and mortality. Despite that, there is a shortage of paediatric cardiologists in Brazil, mainly in the northern and northeastern regions. In this context, the implementation of virtual outpatient clinics with the aid of different telemedicine resources may help in the care of children with heart defects. Methods. Patients under 18 years of age treated in virtual outpatient clinics between January 2013 and May 2014 were selected. They were divided into 2 groups: those who had and those who had not undergone a screening process for CHD in the neonatal period. Clinical and demographic characteristics were collected for further statistical analysis. Results. A total of 653 children and teenagers were treated in the virtual outpatient clinics. From these, 229 had undergone a neonatal screening process. Fewer abnormalities were observed on the physical examination of the screened patients. Conclusion. The implementation of pediatric cardiology virtual outpatient clinics can have a positive impact in the care provided to people in areas with lack of skilled professionals. PMID- 26265914 TI - Surgical and Pathological Changes after Radiofrequency Ablation of Thyroid Nodules. AB - Background. Radiofrequency ablation (RFA) has been recently advocated as an effective technique for the treatment of symptomatic benign thyroid nodules. It is not known to what extent it may affect any subsequent thyroid surgery and/or histological diagnosis. Materials and Methods. RFA was performed on 64 symptomatic Thy2 nodules (benign nodules) and 6 symptomatic Thy3 nodules (follicular lesions/follicular neoplasms). Two Thy3 nodules regrew after the procedure, and these patients accepted to undergo a total thyroidectomy. Here we present how RFA has affected the operation and the final pathological features of the surgically removed nodules. Results and Conclusions. RFA is effective for the treatment of Thy2 nodules, but it should not be recommended as first-line therapy for the treatment of Thy3 nodules (irrespective of their mutational status), as it delays surgery in case of malignancy. Moreover, it is unknown whether RFA might promote residual tumor progression or neoplastic progression of Thy3 lesions. Nevertheless, here we show for the first time that one session of RFA does not affect subsequent thyroid surgery and/or histological diagnosis. PMID- 26265915 TI - A Novel Mutation in the CYP11B1 Gene Causes Steroid 11beta-Hydroxylase Deficient Congenital Adrenal Hyperplasia with Reversible Cardiomyopathy. AB - Congenital adrenal hyperplasia (CAH) due to steroid 11beta-hydroxylase deficiency is the second most common form of CAH, resulting from a mutation in the CYP11B1 gene. Steroid 11beta-hydroxylase deficiency results in excessive mineralcorticoids and androgen production leading to hypertension, precocious puberty with acne, enlarged penis, and hyperpigmentation of scrotum of genetically male infants. In the present study, we reported 3 male cases from a Saudi family who presented with penile enlargement, progressive darkness of skin, hypertension, and cardiomyopathy. The elder patient died due to heart failure and his younger brothers were treated with hydrocortisone and antihypertensive medications. Six months following treatment, cardiomyopathy disappeared with normal blood pressure and improvement in the skin pigmentation. The underlying molecular defect was investigated by PCR-sequencing analysis of all coding exons and intron-exon boundary of the CYP11B1 gene. A novel biallelic mutation c.780 G>A in exon 4 of the CYP11B1 gene was found in the patients. The mutation created a premature stop codon at amino acid 260 (p.W260 (*) ), resulting in a truncated protein devoid of 11beta-hydroxylase activity. Interestingly, a somatic mutation at the same codon (c.779 G>A, p.W260 (*) ) was reported in a patient with papillary thyroid cancer (COSMIC database). In conclusion, we have identified a novel nonsense mutation in the CYP11B1 gene that causes classic steroid 11beta hydroxylase deficient CAH. Cardiomyopathy and cardiac failure can be reversed by early diagnosis and treatment. PMID- 26265917 TI - Comment on "Alternate Sequential Suture Tightening: A Novel Technique for Uncontrolled Postpartum Hemorrhage". PMID- 26265916 TI - The Impact of Subject Age, Gender, and Arch Length on Attitudes of Syrian Dentists towards Shortened Dental Arches. AB - Objective. This study aimed to investigate the impact of subject age, gender, and arch length on dentists' attitudes towards unrestored shortened dental arches. Materials and Methods. 93 Syrian dentists were interviewed and presented with 24 scenarios for male and female subjects of different ages and shortened dental arches of varying length. Participants were asked to indicate on a standardized visual analogue scale how they would value the health of the mouth if the posterior space was left unrestored. Results. A value of 0.0 represented the worst possible health state for a mouth and 1.0 represented the best. The highest mean value (0.73) was assigned to a shortened dental arch with missing second molar teeth in the mouth of a 70-year-old subject. A 35-year-old female subject with an extremely shortened dental arch (all molar and premolar teeth are missing) attracted the lowest mean value (0.26). The statistical analysis indicated a significant decrease in the value placed on unrestored shortened dental arches as the number of remaining teeth decreased (p < 0.008). While subject gender had almost no impact on dentists' attitudes towards shortened dental arches, the scenarios for the older shortened dental arch subjects attracted significantly higher values compared to the scenarios for the younger subjects (p < 0.017). Conclusion. Subject age and arch length affect dentists' attitudes towards shortened dental arches, but subject gender does not. PMID- 26265918 TI - Cattle Uterus: A Novel Animal Laboratory Model for Advanced Hysteroscopic Surgery Training. AB - In recent years, due to reduced training opportunities, the major shift in surgical training is towards the use of simulation and animal laboratories. Despite the merits of Virtual Reality Simulators, they are far from representing the real challenges encountered in theatres. We introduce the "Cattle Uterus Model" in the hope that it will be adopted in training courses as a low cost and easy-to-set-up tool. It adds new dimensions to the advanced hysteroscopic surgery training experience by providing tactile sensation and simulating intraoperative difficulties. It complements conventional surgical training, aiming to maximise clinical exposure and minimise patients' harm. PMID- 26265919 TI - 16 Y/O Female with "Watermelon Stomach"? AB - Background. Gastric antral vascular ectasia (GAVE) also known as "watermelon stomach" (WS) is an uncommon cause of gastrointestinal (GI) blood loss. It typically presents in middle aged females. We are presenting a case of GAVE at an unusually early age with atypical symptoms. Case. A previously healthy 16 y/o Caucasian female presented to the ER with a one-month history of upper abdominal pain. Physical examination was benign except tenderness in the epigastric region. There were no significant findings on laboratory data. Upper endoscopy showed incidental findings of linear striae in the antrum indicative of GAVE but histology was equivocal. Discussion. GAVE is a poorly understood but treatable entity and an increasingly identifiable cause of chronic iron deficiency anemia or acute or occult upper GI bleeding. The pathophysiology of GAVE remains unclear. It is an endoscopic finding characterized by longitudinal columns of tortuous red ectatic vessels (watermelon stripes), pathognomonic for WS. Treatment options include endoscopic, pharmacologic, and surgical approaches. Failure to recognize GAVE can result in delayed treatment for years. Our patient with GAVE was unusually young and was diagnosed incidentally. Due to lack of anemia on laboratory examination we elected to monitor her clinically for any future development of anemia. PMID- 26265920 TI - Review of Ethnobotanical, Phytochemical, and Pharmacological Study of Thymus serpyllum L. AB - Thymus serpyllum L. (wild thyme) is a perennial shrub, native to areas of northern and central Europe. Its aerial parts are most frequently used in ethnomedicine (mainly for treating illnesses and problems related to the respiratory and gastrointestinal systems), although recently its essential oils are becoming more popular as an important plant-derived product. The composition of these oils is affected by geographic region, the development stage of the plant, the harvest season, habitat, and climatic conditions. Wild thyme essential oil has an ever-growing number of uses in contemporary medicine due to its pharmacological properties: antioxidative, antimicrobial, and anticancerogenic activities. The antioxidative and antimicrobial properties of the essential oil are related to the synergistic and cumulative effect of its components. In terms of antitumor and cytotoxic activity, further research into the effects of essential oil is necessary, aimed at improving its cytotoxic effects, on the basis of which appropriate medicines can be formulated. Due to its pharmacological properties, the essential oil of wild thyme, a plant used in traditional medicine, represents an important natural resource for the pharmaceutical industry. In addition, it can be a source of natural antioxidants, nutritional supplements, or components of functional foods in the food industry. PMID- 26265922 TI - Evidence-Based Patient Classification for Traditional Chinese Medicine. PMID- 26265921 TI - Updates on Nutraceutical Sleep Therapeutics and Investigational Research. AB - Approximately 50% of the population will suffer from a sleep disorder over the course of their lifetime. There is increasing interest in nutraceuticals for these conditions. The quality of the evidence for the safety and effectiveness of using these supplements to treat sleep disorders varies substantially. In this review, we discuss the data about the effectiveness and safety of six commonly used plant-based sleep therapeutics: caffeine, chamomile, cherries, kava kava, L tryptophan, marijuana, and valerian. We explore both historical uses of each substance and the current state of the literature. PMID- 26265923 TI - Protective Effect of Ethanolic Extract of Grape Pomace against the Adverse Effects of Cypermethrin on Weanling Female Rats. AB - The adverse effect of cypermethrin on the liver and kidney of weanling female rats and the protective effect of ethanolic extract of grape pomace were investigated in the present study. Weanling female rats were given cypermethrin oral at a dose of 25 mg kg(-1) body weight for 28 consecutive days. An additional two Cyp-trated groups received extract at a dose of 100 and 200 mg kg(-1) body weight, respectively, throughout the experimental duration. Three groups more served as extract and control groups. Administration of Cyp resulted in a significant increase in serum marker enzymes, for example, aminotransferases (AST and ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT), and increases the level of urea nitrogen and creatinine. In contrast, Cyp caused significant decrease in levels of total protein and albumin and caused histopathological alterations in liver and kidneys of female rats. Coadministration of the extract to Cyp-treated female rats restored most of these biochemical parameters to within normal levels especially at high dose of extract. However, extract administration to Cyp-treated rats resulted in overall improvement in liver and kidney damage. This study demonstrated the adverse biohistological effects of Cyp on the liver and kidney of weanling female rats. The grape pomace extract administration prevented the toxic effect of Cyp on the above serum parameters. The present study concludes that grape pomace extract has significant antioxidant and hepatorenal protective activity. PMID- 26265924 TI - The Mechanism Underlying the Antibacterial Activity of Shikonin against Methicillin-Resistant Staphylococcus aureus. AB - Shikonin (SKN), a highly liposoluble naphthoquinone pigment isolated from the roots of Lithospermum erythrorhizon, is known to exert antibacterial, wound healing, anti-inflammatory, antithrombotic, and antitumor effects. The aim of this study was to examine SKN antibacterial activity against methicillin resistant Staphylococcus aureus (MRSA). The SKN was analyzed in combination with membrane-permeabilizing agents Tris and Triton X-100, ATPase inhibitors sodium azide and N,N'-dicyclohexylcarbodiimide, and S. aureus-derived peptidoglycan; the effects on MRSA viability were evaluated by the broth microdilution method, time kill test, and transmission electron microscopy. Addition of membrane permeabilizing agents or ATPase inhibitors together with a low dose of SKN potentiated SKN anti-MRSA activity, as evidenced by the reduction of MRSA cell density by 75% compared to that observed when SKN was used alone; in contrast, addition of peptidoglycan blocked the antibacterial activity of SKN. The results indicate that the anti-MRSA effect of SKN is associated with its affinity to peptidoglycan, the permeability of the cytoplasmic membrane, and the activity of ATP-binding cassette (ABC) transporters. This study revealed the potential of SKN as an effective natural antibiotic and of its possible use to substantially reduce the use of existing antibiotic may also be important for understanding the mechanism underlying the antibacterial activity of natural compounds. PMID- 26265925 TI - Comparison of Volatile Components between Raw and Vinegar Baked Radix Bupleuri by GC-MS Based Metabolic Fingerprinting Approach. AB - Radix Bupleuri (RB), also named Chaihu in Chinese, is a commonly used herbal drug in traditional Chinese medicine (TCM), and the processing of RB with vinegar to prepare vinegar-baked Radix Bupleuri (VBRB) has a long history in the clinic of TCM. In the present study, GC-MS coupled with multivariate data analysis was applied to compare the volatile components between crude and two vinegar processed RBs. After vinegar baking, the oil yields were decreased significantly, and the chemical compositions were also changed greatly. The chemical changes included the disappearance or appearance, as well as the content increase or decrease of some volatile compounds. The oil yields of two different VBRBs showed no significant difference but differed markedly in their chemical compositions, suggesting that the type of vinegar exerted great impacts on the vinegar-baking process. Thus, the effect of different vinegars on processing should be further investigated to ensure the therapeutic effect and safety of VBRB in clinic. PMID- 26265926 TI - Intake of Novel Red Clover Supplementation for 12 Weeks Improves Bone Status in Healthy Menopausal Women. AB - Objective. To investigate the effect by which daily consumption of a novel red clover (RC) extract influences bone health, inflammatory status, and cardiovascular health in healthy menopausal women. Design. A 12-week randomized, double-blinded, placebo-controlled trial involving 60 menopausal women receiving a daily dose of 150 mL RC extract containing 37.1 mg isoflavones (33.8 mg as aglycones) or placebo. Methods. Bone parameters were changes in bone mineral density (BMD), bone mineral content (BMC), and T-score at the lumbar spine and femoral neck. Bone turnover (CTx) and inflammatory markers were measured in plasma and finally blood pressure (BP) was evaluated. Results. RC extract had positive effect on bone health, and only the women receiving the placebo experienced a decline in BMD (p < 0.01) at the lumbar spine. T-score at the lumbar spine only decreased in the placebo group (p < 0.01). CTx decreased in the RC group with -9.94 (+/-4.93)%, although not significant. Conclusion. Daily consumption of RC extract over a 12-week period was found to have a beneficial effect on bone health in menopausal women based on BMD and T-score at the lumbar spine and plasma CTx levels. No changes in BP or inflammation markers were found and no side effects were observed. PMID- 26265927 TI - Erratum: Less functional variants of TLR-1/-6/-10 genes are associated with age. AB - [This corrects the article DOI: 10.1186/s12979-015-0034-z.]. PMID- 26265928 TI - Surveillance systems for neglected tropical diseases: global lessons from China's evolving schistosomiasis reporting systems, 1949-2014. AB - Though it has been a focus of the country's public health surveillance systems since the 1950s, schistosomiasis represents an ongoing public health challenge in China. Parallel, schistosomiasis-specific surveillance systems have been essential to China's decades-long campaign to reduce the prevalence of the disease, and have contributed to the successful elimination in five of China's twelve historically endemic provinces, and to the achievement of morbidity and transmission control in the other seven. More recently, an ambitious goal of achieving nation-wide transmission interruption by 2020 has been proposed. This paper details how schistosomiasis surveillance systems have been structured and restructured within China's evolving public health system, and how parallel surveillance activities have provided an information system that has been integral to the characterization of, response to, and control of the disease. With the ongoing threat of re-emergence of schistosomiasis in areas previously considered to have achieved transmission control, a critical examination of China's current surveillance capabilities is needed to direct future investments in health information systems and to enable improved coordination between systems in support of ongoing control. Lessons drawn from China's experience are applied to the current global movement to reduce the burden of helminthiases, where surveillance capacity based on improved diagnostics is urgently needed. PMID- 26265929 TI - High-fructose and high-fat diet-induced insulin resistance enhances atherosclerosis in Watanabe heritable hyperlipidemic rabbits. AB - BACKGROUND: Individuals with insulin resistance and resulting impaired glucose tolerance along with type 2 diabetes showed an increased prevalence of atherosclerosis. Our aim in this study was to address whether diet-induced insulin resistance plays any roles in the development of aortic and coronary atherosclerosis in hyperlipidemic rabbits. METHODS: We fed Watanabe heritable hyperlipidemic (WHHL) rabbits with a high-fructose and high-fat diet (HFFD) with restricted normal calories and compared the lesions of both aortic and coronary atherosclerosis with those of control WHHL rabbits fed a normal chow diet. RESULTS: HFFD-fed WHHL rabbits showed insulin resistance and impaired glucose tolerance accompanied by elevated plasma lipid levels and accumulation of adipose tissue even though their body weight was unchanged compared to the control rabbits. At 8 weeks, the aortic gross lesion area of HFFD-fed WHHL rabbits was increased by 40 % over the controls and their lesions were characterized by increased number of macrophages and smooth muscle cells. At 16 weeks, the lesions of HFFD-fed WHHL rabbits showed more advanced lesions such as lipid core formation and calcification. In addition, coronary atherosclerosis was significantly increased in HFFD-fed WHHL rabbits. CONCLUSIONS: These results suggest that insulin resistance accelerates lesion formation of atherosclerosis. PMID- 26265930 TI - Health of the corporate worker: health risk assessment among staff of a corporate organization in Ghana. AB - INTRODUCTION: Health promotion at the workplace and for workers is important to promote workers' health, improve working environments and work practices. The goal of this analysis was to provide an example of health risk assessment conducted in a large media organization in Ghana for its workers and to identify correlates of health risks identified among different categories of workers. METHODS: This was a cross sectional study of the health risk of staff in a large corporate media organization in Accra, Ghana, conducted in 2012. In all 161 members of staff were screened and records included in the analysis. An abstraction form was used to collect data on age and sex of staff, staff category, self-reported health risk, history of chronic disease and self-rated health status. Measurements included weight, height, Body Mass Index, fasting blood sugar, total cholesterol/ HDL cholesterol and blood pressure. Data were entered into SPSS version 21, and analyzed by simple frequencies, proportions and ratios. Measured health indices were analyzed by mean +/- standard deviation. Significant association between categorical outcome measures were determined with chi-square test at the 95 % confidence level. RESULTS: The sex characteristics of the workers indicated more males than females, male: female sex ratio of 2.3: 1. Close to half of the workers 66 (41.0 %) self-reported history of chronic disease and 40 (24.8 %) self-rated their overall state of health as poor. In all, 31.7 % of workers self-reported hypertension, while measured blood pressure indicated 60.2 % prevalence of diastolic blood pressure. Prevalence of obesity was 63.8 %; 49.1 % of staff had above normal total cholesterol levels and 12.4 % had blood glucose indicative of diabetes. Senior and management staff had relatively higher prevalence of obesity, high blood pressure, above normal cholesterol and fasting blood sugar levels. CONCLUSION: More staff were unaware of their individual health risks and the health risks were higher among senior staff and management members. Adoption of regular health educational and health promotion activities as well as health surveillance procedures is essential to improve health of workers and promote positive social climate at the work place. PMID- 26265931 TI - COP9-Signalosome deneddylase activity is enhanced by simultaneous neddylation: insights into the regulation of an enzymatic protein complex. AB - BACKGROUND: Cullin-RING ubiquitin ligases (CRLs) are regulated by neddylation, which is a post translation modification of the Cullin family proteins. Neddylation of Cul1 activates the ligase through some means of biochemical mechanisms. The rate of neddylation and its extent are regulated by 2 opposing enzymatic processes: neddylation by an enzymatic cascade, and deneddylation by COP9-Signalosome (CSN) complex protein. The mechanism by which COP9-Signalosome catalytic activity is regulated is not well understood. METHODS: We set an in vitro neddylation and deneddylation reaction using as a source for specific COP9/Signalosome deneddylase activity either Hela cells extract or purified Signalosome. Neddylation reaction of either endogenic Cul1 from Hela cells extract or recombinant Cul1 was catalyzed by recombinant neddylation enzymes. Deneddylation rate was tested either simultaneous to neddylation or after termination of neddylation by using an ATP depleting reaction or by directly inhibiting the neddylation activation enzyme named APP-BP1/UBA3 by its specific inhibitor MLN-4924. RESULTS: We demonstrated that neddylation and deneddylation are catalytically engaged and that inhibition of Cul1 neddylation significantly causes a decline in the rate of COP9-Signalosome deneddylase activity. Since neddylation is an ATP consuming reaction we managed to isolate the 2 opposing processes which surprisingly caused a decline in COP9 activity. Using MLN-4924 we demonstrated that direct inhibition of neddylation negatively influences the rate of deneddylation. The hypothesis that phosphorylation controls deneddylation was ruled out by the fact that no change in the rate of deneddylation was exemplified while converting the use of ATP with AMP-PNP. CONCLUSIONS: We demonstrated that deneddylation of Cul1 is positively regulated through direct simultaneous neddylation and is not dependent upon autophosphorylation. Defining the mechanism that regulates neddylation and deneddylation of Cullin proteins is important due to their effect on highly conserved cellular processes. We showed that minor changes in the degree of Cul1 neddylation linearly control the degree of p27 conjugation to ubiquitin, which emphasizes the hypothetic physiologic significance of our findings. PMID- 26265932 TI - SOSORT Award Winner 2015: a multicentre study comparing the SPoRT and ART braces effectiveness according to the SOSORT-SRS recommendations. AB - BACKGROUND: Data comparing different braces for adolescent idiopathic scoliosis (AIS) are scant. The SRS criteria represent some guidelines for comparing results from different studies, but controlled studies are much more reliable. Recently, super-rigid braces have been introduced in clinical practice with the aim of replacing Risser and EDF casts. The aim of the present study is to compare the short-term radiographic results of two super-rigid braces, the ART and the SPORT (Sforzesco) brace. METHODS: A group of consecutive patients with Cobb >40 degrees , Risser 0-4, age >10 treated with the ART brace for 6 months were matched with a group of similar patients taken from a prospective database of patients treated with the Sforzesco brace. Patients were matched according to Cobb severity, pattern and localization of the curve. All patients had a full-time brace prescription (23-24 hours per day) and an indication to perform scoliosis specific exercises and were assessed radiographically both immediately in the brace and after 6 months of treatment out of brace. Curves were analyzed according to the pattern and localization taking into consideration both the in brace correction and the 6-month out-of-brace results. STATISTICAL ANALYSIS: t test, ANOVA, linear regression, alpha set at 0.05. RESULTS: Twenty-six patients were included in the ART brace group, and 26 in the Sforzesco brace group. At baseline, no differences were noted for gender (3 males for each group), age (14.1 +/- 0.3 for ART vs 13.9 +/- 0.3 for Sforzesco), ATR (11.8 +/- 3.2 vs 11.5 +/- 4.2 for thoracic curves and 7.8 +/- 4.0 vs 7.1 +/- 6.1 for lumbar/thoracolumbar), Cobb angle (44.8 +/- 2 vs 45.5 +/- 2 for thoracic; 43.8 +/ 2 vs 46.0 +/- 2 for lumbar/thoracolumbar) or Risser sign (median 2 for both groups). The in-brace correction was slightly better for the ART brace, but didn't reach statistical significance (24.3 +/- 8.5 vs 28.0 +/- 6.8 for thoracic; 23.7 +/- 10.4 vs 29.9 +/- 4.2 for lumbar/thoracolumbar). At 6 months, results were similar both for thoracic (34.4 +/- 10.4 vs34.8 +/- 6.8) and for lumbar/thoracolumbar (32.8 +/- 10.8 vs 36.6 +/- 5.2). Also, with regard to the pattern, results were similar for double major and for thoracic, while there were not enough data for single lumbar to make a comparison. No differences for ATR were found (7.8 +/- 3.2 vs 8.6 +/- 2.9 for thoracic; 4.3 +/- 3.4 vs 4.3 +/- 3.7 for lumbar/thoracolumbar). CONCLUSION: These two super-rigid braces showed similar short-term results, despite the better in-brace correction for lumbar curves shown by the ART brace. According to our data, the asymmetric design showed results similar to the symmetric one. After these preliminary data, further studies are needed to check end growth results and the impact of compliance, rigidity of curve, exercise and assessing quality of life. PMID- 26265933 TI - Erratum to: Inferring interaction type in gene regulatory networks using co expression data. AB - [This corrects the article DOI: 10.1186/s13015-015-0054-4.]. PMID- 26265934 TI - p16(INK4a)/Ki-67 dual stain cytology for cervical cancer screening in Thika district, Kenya. AB - BACKGROUND: The identification of suited early detection tests is one among the multiple requirements to reduce cervical cancer incidence in developing countries. METHODS: We evaluated p16(INK4a)/Ki-67 dual-stain cytology in a screening population in Thika district, Kenya and compared it to high-risk human papillomavirus (HR-HPV) DNA testing and visual inspection by acetic acid (VIA) and Lugol's iodine (VILI). RESULTS: Valid results for all tests could be obtained in 477 women. 20.9 % (100/477) were tested positive for HR-HPV DNA, 3.1 % (15/477) had positive VIA/VILI and 8.2 % (39/477) positive p16(INK4a)/Ki-67 cytology. Of 22 women that showed up for colposcopy and biopsy, 6 women were diagnosed with CIN3 and two with CIN2. All women with CIN2/3 were negative in VIA/VILI screening and positive by HR-HPV DNA testing. But HPV was also positive in 91.7 % (11/12) of women with normal histology. p16(INK4a)/Ki-67 cytology was positive in all 6 women with CIN3, in one of the two CIN2 and in only 8.3 % (1/12) of women with normal histology. CONCLUSIONS: p16(INK4a)/Ki-67 cytology is an interesting test for further studies in developing countries, since our findings point to a lower fraction of false positive test results using p16(INK4a)/Ki-67 cytology compared to HPV DNA testing in a Kenyan screening population. VIA/VILI missed all histology-proven CIN2/3. PMID- 26265935 TI - Perceptions, attitude and use of family planning services in post conflict Gulu district, northern Uganda. AB - BACKGROUND: Northern Uganda was severely affected by two decades of civil war that led to the displacement and encampment of an estimated 1.6 million inhabitants. The objective of this study was to assess community perspectives, attitude and factors that influence use of family planning (FP) services in post conflict Gulu district. METHODS: We conducted a cross sectional study using multistage sampling technique. All three counties in the district were purposely selected. Two sub-counties per county and four parishes per sub-county were randomly selected. A total of 24 parishes (clusters) and 21 adult heads of households per cluster were randomly selected and interviewed. In total, 500 adults 117 males (23.4 %) and 383 females (76.6 %) were interviewed. We conducted 8 focus group discussions and 6 key informant interviews with family planning managers and service providers. Quantitative data were entered in EPI data and analyzed using STATA version 12. Qualitative data were analyzed manually using thematic content analysis. RESULTS: Contraceptive prevalence rate was 47.5 %. Communities perceive FP as acceptable, beneficial and geographically, temporally and financially accessible. Factors associated with FP use included age 26-35 years (AOR 1.92, 95 % CI 1.18-3.10, p = 0.008), and 36-45 years (AOR 2.27, 95 % CI 1.21-4.25, p = 0.010), rural residence (AOR = 0.41, 95 % CI 0.24-0.71, p = 0.001), cohabitation (AOR = 2.77, 95 % CI 1.15-6.65, p = 0.023), and being a farmer (AOR 0.59, 95 % CI 0.35-0.97, p = 0.037). The main reason for non-use of family planning was fear of side effects 88.2 %. The main source of FP services was government health facilities 94.2 %. CONCLUSION: Use of family planning is relatively high and communities view FP services as acceptable, beneficial and accessible. Family planning use is mainly determined by age, residence, occupation and marital status. Fear of side effects is the main impediment to FP use. There is need to increase awareness and effectively manage side effects of family planning in the settings. PMID- 26265938 TI - A tale of two specialties: primary care and public health. PMID- 26265936 TI - Parallel use of shake flask and microtiter plate online measuring devices (RAMOS and BioLector) reduces the number of experiments in laboratory-scale stirred tank bioreactors. AB - BACKGROUND: Conventional experiments in small scale are often performed in a 'Black Box' fashion, analyzing only the product concentration in the final sample. Online monitoring of relevant process characteristics and parameters such as substrate limitation, product inhibition and oxygen supply is lacking. Therefore, fully equipped laboratory-scale stirred tank bioreactors are hitherto required for detailed studies of new microbial systems. However, they are too spacious, laborious and expensive to be operated in larger number in parallel. Thus, the aim of this study is to present a new experimental approach to obtain dense quantitative process information by parallel use of two small-scale culture systems with online monitoring capabilities: Respiration Activity MOnitoring System (RAMOS) and the BioLector device. RESULTS: The same 'mastermix' (medium plus microorganisms) was distributed to the different small-scale culture systems: 1) RAMOS device; 2) 48-well microtiter plate for BioLector device; and 3) separate shake flasks or microtiter plates for offline sampling. By adjusting the same maximum oxygen transfer capacity (OTRmax), the results from the RAMOS and BioLector online monitoring systems supplemented each other very well for all studied microbial systems (E. coli, G. oxydans, K. lactis) and culture conditions (oxygen limitation, diauxic growth, auto-induction, buffer effects). CONCLUSIONS: The parallel use of RAMOS and BioLector devices is a suitable and fast approach to gain comprehensive quantitative data about growth and production behavior of the evaluated microorganisms. These acquired data largely reduce the necessary number of experiments in laboratory-scale stirred tank bioreactors for basic process development. Thus, much more quantitative information is obtained in parallel in shorter time. PMID- 26265939 TI - The future London Journal of Primary Care. PMID- 26265941 TI - Can community-oriented primary care help GP commissioning? PMID- 26265940 TI - Developing a community-oriented health and well-being service for Cumbria, through clinical commissioning: personal reflections. AB - This article includes my observations as Director of Public Health in Cumbria of success factors of clinical commissioning after a five-year experiment. PMID- 26265942 TI - NHS Future Forum. AB - Professor Steve Field led the Future Forum listening exercise during the pause in the progress of the Health and Social Care bill earlier this year. The Forum made a number of recommendations which led to significant amendments to the bill. Following this successful method of engagement, the Prime Minister David Cameron asked Professor Field to lead a second phase of the Forum looking at four new workstreams. The conclusions from three of the workstreams will inform the development of specific pieces of government policy, and in the case of the integration workstream consider wider issues about joined up care. PMID- 26265937 TI - Artificial cell-cell communication as an emerging tool in synthetic biology applications. AB - Cell-cell communication is a widespread phenomenon in nature, ranging from bacterial quorum sensing and fungal pheromone communication to cellular crosstalk in multicellular eukaryotes. These communication modes offer the possibility to control the behavior of an entire community by modifying the performance of individual cells in specific ways. Synthetic biology, i.e., the implementation of artificial functions within biological systems, is a promising approach towards the engineering of sophisticated, autonomous devices based on specifically functionalized cells. With the growing complexity of the functions performed by such systems, both the risk of circuit crosstalk and the metabolic burden resulting from the expression of numerous foreign genes are increasing. Therefore, systems based on a single type of cells are no longer feasible. Synthetic biology approaches with multiple subpopulations of specifically functionalized cells, wired by artificial cell-cell communication systems, provide an attractive and powerful alternative. Here we review recent applications of synthetic cell-cell communication systems with a specific focus on recent advances with fungal hosts. PMID- 26265943 TI - Improving the public health/primary care partnership: a perspective from NHS Hounslow. AB - The purpose of this article is to set out the importance of the public health role for clinical commissioning groups as they develop their role as commissioners and work to improve health and reduce inequalities. The article describes the experience of Public Health Hounslow that supports the local authority (Local Borough of Hounslow) and the emerging Hounslow Clinical Commissioning Group (HCCG). I review the roles of public health and primary care within the context of the current NHS reforms, and set out the rationale for the best ways to facilitate public health/primary care partnerships. PMID- 26265944 TI - University-linked localities. AB - In this article, we propose that reframing the old concept of 'academic general practices' as 'university-linked localities' will help to integrate the work of those leading commissioning, education, research and public health. It will provide a 'playground' for different disciplines to creatively interact for the benefit of all. PMID- 26265945 TI - West London Primary Care Consortium for Research and Innovation. PMID- 26265946 TI - Boundary spanning and health: invitation to a learning community. AB - Boundaries, which are essential for the healthy functioning of individuals and organisations, can become problematic when they limit creative thought and action. In this article, we present a framework for promoting health across boundaries and summarise preliminary insights from experience, conversations and reflection on how the process of boundary spanning may affect health. Boundary spanning requires specific individual qualities and skills. It can be facilitated or thwarted by organisational context. Boundary spanning often involves risk, but may reap abundant rewards. Boundary spanning is necessary to optimise health and health care. Exploring the process, the landscape and resources that enable boundary spanning may yield new opportunities for advancing health. We invite boundary spanners to join in a learning community to advance understanding and health. PMID- 26265947 TI - A global perspective on the education and training of primary care and public health professionals. AB - Background There is a critical shortage of health workers globally, which is not just a problem for low- and middle-income countries, but needs to be tackled through shared action. At the same time, public policy around the world is responding to changing health needs, social trends and technological possibilities by placing ever greater emphasis on primary care and public health, the interconnections between them and their relationships with other disciplines. All these themes mean that a new approach to the education and training of health workers is required. Setting Global, but with relevance to the UK. Question The education and training of professionals in public health and primary care need to adapt to the changing epidemiological, social, technological and policy environment, as well as to health worker shortages and resource constraints. Methods This article brings together the results of reviews undertaken by the Global Health Workforce Alliance taskforce on scaling up the education and training of the health workforce and the Lancet Commission 'Health professionals for a new century - transforming education to strengthen health systems in an interdependent world' (of both of which the author was a member) with the author's own experiences working in Africa, Asia and North America as well as in the UK. Results There are obvious differences in the needs and capabilities of health systems in different countries, but whatever the context - and whether they are high-, low- or middle-income countries - there are many similarities in the approach that is needed to educate and train professional and non professional health workers, and a great deal that all countries can learn from each other. Conclusion/discussion As the NHS enters a new phase in the continuing development of general practitioners as commissioners and providers there is a need to look for insights from around the world and to develop a new approach to educating and training primary care and public health professionals which takes account of this global perspective and global learning. PMID- 26265948 TI - Editorial response to Nigel Crisp: Is there consensus to re-design professional medical education? PMID- 26265949 TI - International sources of learning for the organisation of primary care. AB - This article explores the potential to learn from emerging international models of primary care organisation. It examines a series of exemplars from Southern Europe and Latin America which may help support moves towards a 'new localism' in the public management of primary care. Six lessons for the UK are identified. PMID- 26265950 TI - Integrating primary care and public health: learning from the Brazilian way. AB - After a long history of vertical programming, specialisation and disintegration, general practitioners are now being urged to take on wider commissioning and public health responsibilities. The support structures are not in place, and integration of primary care with good public health practice is new territory. Innovation can be found in unlikely places. The Brazilian government has a 20 year history of a nationwide, integrated, comprehensive, community health programme that seamlessly bridges two important interfaces - between the community and primary care, and between primary care and public health. Some elements of this approach could be translated into the UK and would likely bring about improved clinical care, cost savings, improved understanding of local epidemiological variations and therefore commissioning. Understanding this approach is the first step to a new way of integrated commissioning, spanning and not reinforcing traditional clinical domains. PMID- 26265951 TI - Partnerships between primary healthcare and population health: preventing chronic disease in Australia. AB - In Australia, partnership working between public health and primary healthcare for the prevention and management of chronic disease has been developing incrementally since the 2003 consensus statement developed by the Joint Advisory Group of the General Practice Partnership Advisory Council and the National Public Health Partnership Group. Australia's first national primary healthcare strategy (2010) provides a new opportunity to further develop this partnership, including multidisciplinary team-working in general practice for chronic disease prevention, and a new primary care organisation to oversee population health planning and health promotion. The needs of vulnerable and disadvantaged groups will be a central focus of the new planning structures. However, major barriers continue to frustrate collaborative population based planning and service development. Conclusion The jury is still out on how effective the partnership between state funded public health service and the new nationally funded primary care organisations will be. There is significant overlap in their functions, but few formal mechanisms for collaboration have been as yet established. PMID- 26265952 TI - Creating a patient-led NHS: some ethical and epistemological challenges. AB - This article responds to the Coalition government's recent Open Public Services White Paper and to proposals which call for the creation of a 'patient-led NHS' which will, wherever possible, seek to give patients direct control over the services they receive, through a greater degree of choice and participation. Its central contention is that affording patients greater influence over the consultation and commissioning processes will require the NHS to accommodate and respond to the beliefs, values and agendas of patients, as well as those of medical professionals and policy makers. Since it cannot be assumed that professionals and patients will share the same beliefs, values and agendas, the creation of a system of patient-led services has the potential to bring disagreement between professionals and patients to a head, particularly within the consultation and commissioning processes. Thus, a set of complex epistemic and ethical challenges accompanies the proposed creation of a 'patient-led NHS', greater awareness of which will be necessary for the successful implementation of such reforms. PMID- 26265953 TI - An account of my life. AB - This is the eighth instalment of the autobiography of John Horder. It was originally written for his grandchildren to read. John is a founding father of modern general practice. He was doing his medical finals when the NHS was founded in 1948 and has been an active advocate of whole person, family and community oriented general practice ever since. He was one of the two founders of the Leeuwenhorst European Study Group that defined the job description of a general practitioner in 1974. He was president of the Royal College of General Practitioners between 1979 and 1982. He assisted the setting up of general practice educational bodies in several western European countries, especially Yugoslavia and Portugal. He has been a tireless supporter of inter-disciplinary learning and founded the Centre for the Advancement of Inter-professional Education (CAIPE) in 1987. He lives in Primrose Hill with his wife Elizabeth June, who was also his partner in general practice. Abridged by Layla Stock (Ealing PCT). PMID- 26265954 TI - Reflection. PMID- 26265955 TI - Miasmatists and health reforms. PMID- 26265956 TI - General practitioners and fitness for work. PMID- 26265957 TI - Prenatal parental tobacco smoking, gene specific DNA methylation, and newborns size: the Generation R study. AB - BACKGROUND: Deleterious effects of prenatal tobacco smoking on fetal growth and newborn weight are well-established. One of the proposed mechanisms underlying this relationship is alterations in epigenetic programming. We selected 506 newborns from a population-based prospective birth cohort in the Netherlands. Prenatal parental tobacco smoking was assessed using self-reporting questionnaires. Information on birth outcomes was obtained from medical records. The deoxyribonucleic acid (DNA) methylation of the growth genes IGF2DMR and H19 was measured in newborn umbilical cord white blood cells. Associations were assessed between parental tobacco smoking and DNA methylation using linear mixed models and adjusted for potential confounders. RESULTS: The DNA methylation levels of IGF2DMR and H19 in the non-smoking group were median (90 % range), 54.0 % (44.6-62.0), and 30.0 % (25.5-34.0), in the first trimester only smoking group 52.2 % (44.5-61.1) and 30.8 % (27.1-34.1), and in the continued smoking group 51.6 % (43.9-61.3) and 30.2 % (23.7-34.8), respectively. Continued prenatal maternal smoking was inversely associated with IGF2DMR methylation (beta = -1.03, 95 % CI -1.76; -0.30) in a dose-dependent manner (P-trend = 0.030). This association seemed to be slightly more profound among newborn girls (beta = 1.38, 95 % CI -2.63; -0.14) than boys (beta = -0.72, 95 % CI -1.68; 0.24). H19 methylation was also inversely associated continued smoking <5 cigarettes/day (beta = -0.96, 95 % CI -1.78; -0.14). Moreover, the association between maternal smoking and newborns small for gestational age seems to be partially explained by IGF2DMR methylation (beta = -0.095, 95 % CI -0.249; -0.018). Among non-smoking mothers, paternal tobacco smoking was not associated with IGF2DMR or H19 methylation. CONCLUSIONS: Maternal smoking is inversely associated with IGF2DMR methylation in newborns, which can be one of the underlying mechanisms through which smoking affects fetal growth. PMID- 26265958 TI - Effect of an Echinacea-Based Hot Drink Versus Oseltamivir in Influenza Treatment: A Randomized, Double-Blind, Double-Dummy, Multicenter, Noninferiority Clinical Trial. AB - BACKGROUND: Echinacea has antiviral activity against influenza viruses in vitro and has traditionally been used for treatment of colds and flu. OBJECTIVES: This randomized, double-blind, double-dummy, multicenter, controlled clinical trial compared a new echinacea formulation with the neuraminidase inhibitor oseltamivir, the gold standard treatment for influenza. METHODS: Following informed consent, 473 patients with early influenza symptoms (<=48 hours) were recruited in primary care in the Czech Republic and randomized to either 5 days of oseltamivir followed by 5 days of placebo, or 10 days of an Echinacea purpurea based formulation called Echinaforce Hotdrink (A. Vogel Bioforce AG, Roggwil, Switzerland). The proportion of recovered patients (influenza symptoms rated as absent or mild in the evening) was analyzed for noninferiority between treatment groups using a generalized Wilcoxon test with significance level alpha = 0.05 (2 sided) and using a CI approach in the per-protocol sample. RESULTS: Recovery from illness was comparable in the 2 treatment groups at 1.5% versus 4.1% after 1 day, 50.2% versus 48.8% after 5 days, and 90.1% versus 84.8% after 10 days of treatment with Echinaforce Hotdrink and oseltamivir, respectively. Noninferiority was demonstrated for each day and overall (95% CI, 0.487-0.5265 by generalized Wilcoxon test). Very similar results were obtained in the group with virologically confirmed influenza virus infections and in a retrospective analysis during the peak influenza period. The incidence of complications was lower with Echinaforce Hotdrink than with oseltamivir (2.46% vs 6.45%; P = 0.076) and fewer adverse events (particularly nausea and vomiting) were observed with Echinaforce Hotdrink. CONCLUSIONS: Echinaforce Hotdrink is as effective as oseltamivir in the early treatment of clinically diagnosed and virologically confirmed influenza virus infections with a reduced risk of complications and adverse events. It appears to be an attractive treatment option, particularly suitable for self-care. Clinical trial identifier: Eudra-CT: 2010-021571-88. (Curr Ther Res Clin Exp. 2015; 77:66-72). PMID- 26265959 TI - Approach to Management of Intravascular Missile Emboli: Review of the Literature and Case Report. PMID- 26265960 TI - Poisonings with Suicidal Intent Aged 0-21 Years Reported to Poison Centers 2003 12. AB - INTRODUCTION: Few studies explore the clinical features of youth suicide by poisoning. The use of both social and clinical features of self-poisoning with suicidal intent could be helpful in enhancing existing and creating new prevention strategies. We sought to characterize self-poisonings with suicide intent in ages 0 to 21 years reported to three regional poison control centers from 2003-2012. METHODS: This study was a blinded retrospective review of intentional self-poisonings by those age 21 or younger captured by the Poison Information Control Network. Age, sex, substance(s) used, medical outcome, management site, clinical effects, and therapies were described using counts and percentages and analyzed using chi-square tests. We analyzed the medical outcome ranging from no effect to death using the Wilcoxon rank-sum test. Serious medical outcome was defined as death or major outcome. RESULTS: We analyzed a total of 29,737 cases. The majority were females (20,945;70.5%), of whom 274 (1.3%) were pregnant. Most cases were 15-18 year olds (15,520;52.2%). Many experienced no effects (9,068;30.5%) or minor medical outcomes (8,612;29%). Males had more serious medical outcomes (p<0.0001), but females were more likely to be admitted to a critical care unit (p<0.0001). There were 17 deaths (0.06%), most in males (10;p=0.008). Of the 52 substances reported in the death cases, 12 (23.1%) were analgesics. In eight (47.1%) of the deaths, over two substances were used. Overall, drowsiness/lethargy (7,097;19.3%) and single-dose charcoal (8,815;16.3%) were frequently reported. Nearly 20% were admitted to critical care units (5,727;19.3%) and 28.7% went to psychiatric facilities (8,523). Of those admitted to hospitals (8,203), nearly 70% (5,727) required critical care units. Almost half <10 years old were evaluated and released (43;47.2%). Of the 114 reported substances for this population, 22.8% involved psychotropic medications, 15.8% analgesics, and 14% Attention Deficit-Hyperactive Disorder (ADHD) medications. Analgesics (13,539;33.6%) were the most common medication category used by all age groups. Typically only one substance (20,549;69.1%) was used. CONCLUSION: Undiagnosed ADHD may be a potential underlying cause for self-harming behaviors in the very young. Gender-specific suicide prevention strategies may be more effective at identifying those at risk than traditional measures alone. Further study into admitting practices by emergency physicians is needed to understand the difference in critical care admission rates based on gender. Once identified to be at-risk for suicidal behavior, access to analgesics and psychotropics should be monitored by care-givers especially in those between the ages of 15-18. PMID- 26265961 TI - Prehospital Evaluation of Effusion, Pneumothorax, and Standstill (PEEPS): Point of-care Ultrasound in Emergency Medical Services. AB - INTRODUCTION: In the United States, there are limited studies regarding use of prehospital ultrasound (US) by emergency medical service (EMS) providers. Field diagnosis of life-threatening conditions using US could be of great utility. This study assesses the ability of EMS providers and students to accurately interpret heart and lung US images. METHODS: We tested certified emergency medical technicians (EMT-B) and paramedics (EMT-P) as well as EMT-B and EMT-P students enrolled in prehospital training programs within two California counties. Participants completed a pre-test of sonographic imaging of normal findings and three pathologic findings: pericardial effusion, pneumothorax, and cardiac standstill. A focused one-hour lecture on emergency US imaging followed. Post tests were given to all EMS providers immediately following the lecture and to a subgroup one week later. RESULTS: We enrolled 57 prehospital providers (19 EMT-B students, 16 EMT-P students, 18 certified EMT-B, and 4 certified EMT-P). The mean pre-test score was 65.2%+/-12.7% with mean immediate post-test score of 91.1%+/ 7.9% (95% CI [22%-30%], p<0.001). Scores significantly improved for all three pathologic findings. Nineteen subjects took the one-week post-test. Their mean score remained significantly higher: pre-test 65.8%+/-10.7%; immediate post-test 90.5%+/-7.0% (95% CI [19%-31%], p<0.001), one-week post-test 93.1%+/-8.3% (95% CI [21%-34%], p<0.001). CONCLUSION: Using a small sample of EMS providers and students, this study shows the potential feasibility for educating prehospital providers to accurately identify images of pericardial effusion, pneumothorax, and cardiac standstill after a focused lecture. PMID- 26265962 TI - Recommendations from the Council of Residency Directors (CORD) Social Media Committee on the Role of Social Media in Residency Education and Strategies on Implementation. AB - Social media (SM) is a form of electronic communication through which users create online communities and interactive platforms to exchange information, ideas, messages, podcasts, videos, and other user-generated content. Emergency medicine (EM) has embraced the healthcare applications of SM at a rapid pace and continues to explore the potential benefit for education. Free Open Access Meducation has emerged from the ever-expanding collection of SM interactions and now represents a virtual platform for sharing educational media. This guidance document constitutes an expert consensus opinion for best practices in the use of SM in EM residency education. The goals are the following: 1) Recommend adoption of SM as a valuable graduate medical education (GME) tool, 2) Provide advocacy and support for SM as a GME tool, and 3) Recommend best practices of educational deliverables using SM. These guidelines are intended for EM educators and residency programs for the development and use of a program-specific SM presence for residency education, taking into account appropriate SM stewardship that adheres to institution-specific guidelines, content management, Accreditation Council for GME milestone requirements, and integration of SM in EM residency curriculum to enhance the learner's experience. Additionally, potential obstacles to the uptake of SM as an educational modality are discussed with proposed solutions. PMID- 26265963 TI - Demographic, Operational, and Healthcare Utilization Factors Associated with Emergency Department Patient Satisfaction. AB - INTRODUCTION: The primary aim of this study was to determine which objectively measured patient demographics, emergency department (ED) operational characteristics, and healthcare utilization frequencies (care factors) were associated with patient satisfaction ratings obtained from phone surveys conducted by a third-party vendor for patients discharged from our ED. METHODS: This is a retrospective, observational analysis of data obtained between September 2011 and August 2012 from all English- and Spanish-speaking patients discharged from our ED who were contacted by a third-party patient satisfaction vendor to complete a standardized nine-item telephone survey by a trained phone surveyor. We linked data from completed surveys to the patient's electronic medical record to abstract additional demographic, ED operational, and healthcare utilization data. We used univariate ordinal logistic regression, followed by two multivariate models, to identify significant predictors of patient satisfaction. RESULTS: We included 20,940 patients for analysis. The overall patient satisfaction ratings were as follows: 1=471 (2%); 2=558 (3%); 3=2,014 (10%), 4=5,347 (26%); 5=12,550 (60%). Factors associated with higher satisfaction included race/ethnicity (Non-Hispanic Black; Hispanic patients), age (patients >=65), insurance (Medicare), mode of arrival (arrived by bus or on foot), and having a medication ordered in the ED. Patients who felt their medical condition did not improve, those treated in our ED behavioral health area, and those experiencing longer wait times had reduced satisfaction. CONCLUSION: These findings provide a basis for development and evaluation of targeted interventions that could be used to improve patient satisfaction in our ED. PMID- 26265964 TI - Differences in Presentation and Management of Pediatric Facial Lacerations by Type of Health Insurance. AB - INTRODUCTION: Limited data are available regarding differences in presentation and management of pediatric emergency department (PED) patients based on insurance status. The objective of the study was to assess the difference in management of pediatric facial lacerations based on medical insurance status. METHODS: We conducted a retrospective cohort study with universal sampling of patients with facial lacerations who were treated in an urban PED (45K visits/year) over a one-year period. Demographic features and injury characteristics for patients with commercial (private) insurance and those with Medicaid or Medicare (public) insurance were compared. RESULTS: Of 1235 children included in the study, 667 (54%) had private insurance and 485 (39%) had public insurance. The two groups did not differ in age or gender, arrival by ambulance, location of injury occurrence, mechanism of injury, part of face involved, length or depth of laceration, use of local anesthetic, or method of repair but differed in acuity assigned at triage. Patients with public insurance were found less likely to have subspecialty consultation in bivariable (OR=0.41, 95% CI [0.24 0.68]) and multivariable logistic regression analyses (OR=0.45, 95% CI [0.25 0.78]). Patients with public insurance received procedural sedation significantly less often than those with private insurance (OR=0.48, 95% CI [0.29-0.76]). This difference was not substantiated in multivariable models (OR=0.74, 95% CI [0.40 1.31]). CONCLUSION: Patients with public insurance received less subspecialty consultation compared to privately insured patients despite a similarity in the presentation and characteristics of their facial lacerations. The reasons for these disparities require further investigation. PMID- 26265965 TI - Predictors of Linkage to Care for Newly Diagnosed HIV-Positive Adults. AB - INTRODUCTION: Linkage to care following a human immunodeficiency virus (HIV) diagnosis is critical. In the U.S. only 69% of patients are successfully linked to care, which results in delayed receipt of antiretroviral therapy leading to immune system dysfunction and risk of transmission to others. METHODS: We evaluated predictors of failure to link to care at a large urban healthcare center in Philadelphia in order to identify potential intervention targets. We conducted a cohort study between May 2007 and November 2011 at hospital affiliated outpatient clinics, emergency departments (EDs), and inpatient units. RESULTS: Of 87 patients with a new HIV diagnosis, 63 (72%) were linked to care: 23 (96%) from the outpatient setting and 40 (63%) from the hospital setting (ED or inpatient) (p<0.01). Those who were tested in the hospital-based settings were more likely to be black (p=0.01), homeless (p=0.03), and use alcohol or drugs (p=0.03) than those tested in the outpatient clinics. Patients tested in the ED or inpatient units had a 10.9 fold (p=0.03) higher odds of failure to link compared to those diagnosed in an outpatient clinic. When testing site was controlled, unemployment (OR 12.2;p<0.01) and substance use (OR 6.4;p<0.01) were associated with failure to link. CONCLUSION: Our findings demonstrate the comparative success of linkage to care in outpatient medical clinics versus hospital-based settings. This study both reinforces the importance of routine opt out HIV testing in outpatient practices, and demonstrates the need to better understand barriers to linkage. PMID- 26265966 TI - How do Medical Societies Select Science for Conference Presentation? How Should They? AB - INTRODUCTION: Nothing has been published to describe the practices of medical societies in choosing abstracts for presentations at their annual meetings. We surveyed medical societies to determine their practices, and also present a theoretical analysis of the topic. METHODS: We contacted a convenience sample of large U.S. medical conferences, and determined their approach to choosing abstracts. We obtained information from web sites, telephone, and email. Our theoretical analysis compares values-based and empirical approaches for scoring system development. RESULTS: We contacted 32 societies and obtained data on 28 (response rate 88%). We excluded one upon learning that research was not presented at its annual meeting, leaving 27 for analysis. Only 2 (7%) made their abstract scoring process available to submitters. Reviews were blinded in most societies (21;78%), and all but one asked reviewers to recuse themselves for conflict of interest (96%). All required >=3 reviewers. Of the 24 providing information on how scores were generated, 21 (88%) reported using a single gestalt score, and three used a combined score created from pooled domain specific sub-scores. We present a framework for societies to use in choosing abstracts, and demonstrate its application in the development of a new scoring system. CONCLUSIONS: Most medical societies use subjective, gestalt methods to select research for presentation at their annual meetings and do not disclose to submitters the details of how abstracts are chosen. We present a new scoring system that is transparent to submitters and reviewers alike with an accompanying statement of values and ground rules. We discuss the challenges faced in selecting abstracts for a large scientific meeting and share the values and practical considerations that undergird the new system. PMID- 26265967 TI - Validation of ICD-9 Codes for Stable Miscarriage in the Emergency Department. AB - INTRODUCTION: International Classification of Disease, Ninth Revision (ICD-9) diagnosis codes have not been validated for identifying cases of missed abortion where a pregnancy is no longer viable but the cervical os remains closed. Our goal was to assess whether ICD-9 code "632" for missed abortion has high sensitivity and positive predictive value (PPV) in identifying patients in the emergency department (ED) with cases of stable early pregnancy failure (EPF). METHODS: We studied females ages 13-50 years presenting to the ED of an urban academic medical center. We approached our analysis from two perspectives, evaluating both the sensitivity and PPV of ICD-9 code "632" in identifying patients with stable EPF. All patients with chief complaints "pregnant and bleeding" or "pregnant and cramping" over a 12-month period were identified. We randomly reviewed two months of patient visits and calculated the sensitivity of ICD-9 code "632" for true cases of stable miscarriage. To establish the PPV of ICD-9 code "632" for capturing missed abortions, we identified patients whose visits from the same time period were assigned ICD-9 code "632," and identified those with actual cases of stable EPF. RESULTS: We reviewed 310 patient records (17.6% of 1,762 sampled). Thirteen of 31 patient records assigned ICD-9 code for missed abortion correctly identified cases of stable EPF (sensitivity=41.9%), and 140 of the 142 patients without EPF were not assigned the ICD-9 code "632"(specificity=98.6%). Of the 52 eligible patients identified by ICD-9 code "632," 39 cases met the criteria for stable EPF (PPV=75.0%). CONCLUSION: ICD-9 code "632" has low sensitivity for identifying stable EPF, but its high specificity and moderately high PPV are valuable for studying cases of stable EPF in epidemiologic studies using administrative data. PMID- 26265968 TI - Importance of Decision Support Implementation in Emergency Department Vancomycin Dosing. AB - INTRODUCTION: The emergency department (ED) plays a critical role in the management of life-threatening infection. Prior data suggest that ED vancomycin dosing is frequently inappropriate. The objective is to assess the impact of an electronic medical record (EMR) intervention designed to improve vancomycin dosing accuracy, on vancomycin dosing and clinical outcomes in critically ill ED patients. METHODS: Retrospective before-after cohort study of all patients (n=278) treated with vancomycin in a 60,000-visit Midwestern academic ED (March 2008 and April 2011) and admitted to an intensive care unit. The primary outcome was the proportion of vancomycin doses defined as "appropriate" based on recorded actual body weight. We also evaluated secondary outcomes of mortality and length of stay. RESULTS: The EMR dose calculation tool was associated with an increase in mean vancomycin dose ([14.1+/-5.0] vs. [16.5+/-5.7] mg/kg, p<0.001) and a 10.3% absolute improvement in first-dose appropriateness (34.3% vs. 24.0%, p=0.07). After controlling for age, gender, methicillin-resistant staphylococcus aureus infection, and Acute Physiology and Chronic Health Evaluation II score, 28 day in-hospital mortality (odds ratio OR 1.72; 95% CI [0.76-3.88], p=0.12) was not affected. CONCLUSION: A computerized decision-support tool is associated with an increase in mean vancomycin dose in critically ill ED patients, but not with a statistically significant increase in therapeutic vancomycin doses. The impact of decision-support tools should be further explored to optimize compliance with accepted antibiotic guidelines and to potentially affect clinical outcome. PMID- 26265969 TI - Point-of-care Ultrasound to Identify Distal Ulnar Artery Thrombosis: Case of Hypothenar Hammer Syndrome. AB - Hypothenar hammer syndrome (HHS) is a rare condition of distal ulnar artery injury and thrombosis secondary to repetitive blunt trauma to the hypothenar area. We present a case of HHS for which point-of-care ultrasound (POCUS) was used as the initial means of imaging, prompting management and disposition without further imaging studies ordered in the emergency department (ED). This case demonstrates the utility of POCUS to aid the Emergency Physician in the diagnosis and management of patients with extremity vascular issues in the ED, and details a rarely seen clinical entity in the ED. PMID- 26265970 TI - Choledochal Cyst Mimicking Gallbladder with Stones in a Six-Year-Old with Right sided Abdominal Pain. AB - Choledochal cysts are rare but serious bile duct abnormalities are found in young children, usually during the first year of life.1 They require urgent surgical intervention due to the risk of developing cholangiocarcinoma.2 Clinicians should consider this diagnosis and perform a point-of-care ultrasound (POCUS) when a child presents to the emergency department (ED) with findings of jaundice, abdominal pain, and the presence of an abdominal mass. We present the case of a six-year-old child presenting only with abdominal pain upon arrival to our ED and was ultimately diagnosed by POCUS to have a choledochal cyst. PMID- 26265972 TI - Esophageal Intubation of an Infant. PMID- 26265971 TI - Prochlorperazine-Induced Hemidystonia Mimicking Acute Stroke. AB - Prochlorperazine is frequently used in the treatment of refractory nausea and migraines. Known side effects include extrapyramidal symptoms such as akathisia and dystonia. We report a pregnant patient taking prochlorperazine for hyperemesis gravidarum who developed hemidystonia, which triggered an acute code stroke response from prehospital, emergency medicine and neurology providers. We suspect this report to be the first case of prochlorperazine-induced hemidystonia as a stroke mimic. PMID- 26265973 TI - Massive Hematochezia from Ascending Colonic Varices. PMID- 26265974 TI - Open Ring Sign Diagnostic of Multiple Sclerosis in the Emergency Department. PMID- 26265975 TI - Adult Intussusception Secondary to Inflammatory Fibroid Polyp. PMID- 26265976 TI - Leriche Syndrome Presenting with Multisystem Vaso-Occlusive Catastrophe. PMID- 26265977 TI - Norwegian Scabies. PMID- 26265978 TI - Comparison of Preloaded Bougie versus Standard Bougie Technique for Endotracheal Intubation in a Cadaveric Model. AB - INTRODUCTION: We compared intubating with a preloaded bougie (PB) against standard bougie technique in terms of success rates, time to successful intubation and provider preference on a cadaveric airway model. METHODS: In this prospective, crossover study, healthcare providers intubated a cadaver using the PB technique and the standard bougie technique. Participants were randomly assigned to start with either technique. Following standardized training and practice, procedural success and time for each technique was recorded for each participant. Subsequently, participants were asked to rate their perceived ease of intubation on a visual analogue scale of 1 to 10 (1=difficult and 10=easy) and to select which technique they preferred. RESULTS: 47 participants with variable experience intubating were enrolled at an emergency medicine intern airway course. The success rate of all groups for both techniques was equal (95.7%). The range of times to completion for the standard bougie technique was 16.0-70.2 seconds, with a mean time of 29.7 seconds. The range of times to completion for the PB technique was 15.7-110.9 seconds, with a mean time of 29.4 seconds. There was a non-significant difference of 0.3 seconds (95% confidence interval -2.8 to 3.4 seconds) between the two techniques. Participants rated the relative ease of intubation as 7.3/10 for the standard technique and 7.6/10 for the preloaded technique (p=0.53, 95% confidence interval of the difference -0.97 to 0.50). Thirty of 47 participants subjectively preferred the PB technique (p=0.039). CONCLUSION: There was no significant difference in success or time to intubation between standard bougie and PB techniques. The majority of participants in this study preferred the PB technique. Until a clear and clinically significant difference is found between these techniques, emergency airway operators should feel confident in using the technique with which they are most comfortable. PMID- 26265979 TI - Rural Ambulatory Access for Semi-Urgent Care and the Relationship of Distance to an Emergency Department. AB - INTRODUCTION: Availability of timely access to ambulatory care for semi-urgent medical concerns in rural and suburban locales is unknown. Further distance to an emergency department (ED) may require rural clinics to serve as surrogate EDs in their region, and make it more likely for these clinics to offer timely appointments. We determined the availability of urgent (within 48 hours) access to ambulatory care for non-established visiting patients, and assessed the effect of insurance and ability to pay cash on a patient's success in scheduling an appointment in rural and suburban Eastern United States. We also assessed how proximity to EDs and urgent care (UC) facilities influenced access to semi-urgent ambulatory appointments at primary care facilities. METHODS: The Appalachian Trail, which runs from Georgia to Maine, was used as a transect to select 190 rural and suburban primary care clinics located along its entire length. We calculated their location and distance to the nearest hospital-based ED or UC via Google Earth. A sham patient representing a non-established visiting patient called each clinic over a four-month period (2013), requesting an appointment in the next 48 hours for one of three scripted clinical vignettes representing common semi-urgent ambulatory concerns. We randomized the scenarios and insurance statuses (insured vs. uninsured). Each clinic was contacted twice, once with the caller representing an insured patient, once with the caller representing an uninsured patient. When the caller was representing an uninsured patient, any required upfront payment was requested from each clinic. One hundred dollars was used as a cutoff between the uninsured as a distinction between those able to afford substantial upfront sums and those who could not. To determine if proximity to other sources of care impacted a clinic's ability to grant an appointment, distance to the nearest ED or UC was modeled as a dichotomous variable using 30 miles as the divider. RESULTS: Of 380 requests, 96 (25.3%) resulted in appointments within 48 hours. Insured patients and uninsured patients able to pay a substantial amount upfront (>$100) were more likely to book an appointment (p-value <0.001, OR 18, CI [5-154]). Of the 47 clinics that granted uninsured patients appointments 89.3% required some form of payment up front. Farther distances from an ED did not result in greater likelihood of an appointment (OR 1.7, CI [0.4-11.3]). Clinics located within 30 miles of an UC were more likely to grant an appointment (OR 2.45, CI [1.19-5.80]). CONCLUSION: Almost 75% of rural clinics were unable to grant a new appointment for a semi urgent health complaint. Lack of insurance and large upfront charges appear to be significant barriers to rural ambulatory care appointments. Greater distance from an ED does not improve a clinic's ability to see semi-urgent appointments. Clinics located near an UC were more likely to grant an appointment than clinics without close alternative outpatient healthcare options. PMID- 26265981 TI - Daily Oxygen/O3 Treatment Reduces Muscular Fatigue and Improves Cardiac Performance in Rats Subjected to Prolonged High Intensity Physical Exercise. AB - Rats receiving daily intraperitoneal administration of O2 and running on a treadmill covered an average distance of 482.8 +/- 21.8 m/week as calculated during 5-week observation. This distance was increased in rats receiving daily intraperitoneal administration of an oxygen/O3 mixture at a dose of 100; 150; and 300 MUg/kg with the maximum increase being +34.5% at 300 MUg/kg and still present after stopping the administration of oxygen/O3. Oxygen/O3 decreased the mean arterial blood pressure (-13%), the heart rate (-6%), the gastrocnemius and cardiac hypertrophy, and fibrosis and reduced by 49% the left ventricular mass and relative wall thickness measurements. Systolic and diastolic functions were improved in exercised oxygen/O3 rats compared to O2 rats. Oxygen/O3 treatment led to higher MPI index starting from the dose of 150 MUg/kg (p < 0.05) and more effective (+14%) at a dose of 300 MUg/kg oxygen/O3. Oxygen/O3 dose-dependently increased the expression of the antioxidant enzymes Mn-SOD and GPx1 and of eNOS compared to the exercised O2 rats. The same doses resulted in decrease of LDH levels, CPK, TnI, and nitrotyrosine concentration in the heart and gastrocnemius tissues, arguing a beneficial effect of the ozone molecule against the fatigue induced by a prolonged high intensity exercise. PMID- 26265984 TI - Oxidative Stress-Mediated Reperfusion Injury 2014. PMID- 26265982 TI - Plant Natural Products Calycosin and Gallic Acid Synergistically Attenuate Neutrophil Infiltration and Subsequent Injury in Isoproterenol-Induced Myocardial Infarction: A Possible Role for Leukotriene B4 12-Hydroxydehydrogenase? AB - Leukotriene B4 12-hydroxydehydrogenase (LTB4DH) catalyzes the oxidation of proinflammatory LTB4 into less bioactive 12-oxo-LTB4. We recently discovered that LTB4DH was induced by two different natural products in combination. We previously isolated gallic acid from Radix Paeoniae through a bioactivity-guided fractionation procedure. The purpose of this study is to test the hypothesis that LTB4DH inducers may suppress neutrophil-mediated inflammation in myocardial infarction. We first isolated the active compound(s) from another plant, Radix Astragali, by the similar strategy. By evaluating LTB4DH induction, we identified calycosin and formononetin from Radix Astragali by HPLC-ESI-MS technique. We confirmed that gallic acid and commercial calycosin or formononetin could synergistically induce LTB4DH expression in HepG2 cells and human neutrophils. Moreover, calycosin and gallic acid attenuated the effects of LTB4 on the survival and chemotaxis of neutrophil cell culture. We further demonstrated that calycosin and gallic acid synergistically suppressed neutrophil infiltration and protected cardiac integrity in the isoproterenol-induced mice model of myocardial infarction. Calycosin and gallic acid dramatically suppressed isoproterenol induced increase in myeloperoxidase (MPO) activity and malondialdehyde (MDA) level. Collectively, our results suggest that LTB4DH inducers (i.e., calycosin and gallic acid) may be a novel combined therapy for the treatment of neutrophil mediated myocardial injury. PMID- 26265985 TI - Dietary Polyphenols and Their Effects on Cell Biochemistry and Pathophysiology 2014. PMID- 26265983 TI - Protective Effects of Kaempferol against Myocardial Ischemia/Reperfusion Injury in Isolated Rat Heart via Antioxidant Activity and Inhibition of Glycogen Synthase Kinase-3beta. AB - OBJECTIVE: This study aimed to evaluate the protective effect of kaempferol against myocardial ischemia/reperfusion (I/R) injury in rats. METHOD: Left ventricular developed pressure (LVDP) and its maximum up/down rate (+/-dp/dt max) were recorded as myocardial function. Infarct size was detected with 2,3,5 triphenyltetrazolium chloride staining. Cardiomyocyte apoptosis was determined using terminal deoxynucleotidyl nick-end labeling (TUNEL). The levels of creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione/glutathione disulfide (GSH/GSSG) ratio, and tumor necrosis factor-alpha (TNF-alpha) were determined using enzyme linked immunosorbent assay (ELISA). Moreover, total glycogen synthase kinase-3beta (GSK 3beta), phospho-GSK-3beta (P-GSK-3beta), precaspase-3, cleaved caspase-3, and cytoplasm cytochrome C were assayed using Western blot analysis. RESULTS: Pretreatment with kaempferol significantly improved the recovery of LVDP and +/ dp/dt max, as well as increased the levels of SOD and P-GSK-3beta and GSH/GSSG ratio. However, the pretreatment reduced myocardial infarct size and TUNEL positive cell rate, as well as decreased the levels of cleaved caspase-3, cytoplasm cytochrome C, CK, LDH, MDA, and TNF-alpha. CONCLUSION: These results suggested that kaempferol provides cardioprotection via antioxidant activity and inhibition of GSK-3beta activity in rats with I/R. PMID- 26265986 TI - What is the current role of endoscopy in primary sclerosing cholangitis? AB - Endoscopy has important roles in the management of primary sclerosing cholangitis (PSC), ranging from narrowing down the differential diagnoses, screening for complications, determining prognosis and therapy. While the need for a diagnostic endoscopic retrograde cholangiopancreatography (ERCP) may be obviated by a positive magnetic resonance cholangiopancreatography (MRCP), a negative MRCP does not exclude PSC and may therefore necessitate an ERCP, which is traditionally regarded as the gold standard. In this editorial we have not covered the endoscopic management of inflammatory bowel disease in the context of PSC nor of endoscopic surveillance and treatment of portal hypertension complicating PSC. PMID- 26265988 TI - Duodenal adenoma surveillance in patients with familial adenomatous polyposis. AB - Familial adenomatous polyposis (FAP) is a hereditary disorder caused by Adenomatous Polyposis Gene mutations that lead to the development of colorectal polyps with great malignant risk throughout life. Moreover, numerous extracolonic manifestations incorporate different clinical features to produce varied individual phenotypes. Among them, the occurrence of duodenal adenomatous polyps is considered an almost inevitable event, and their incidence rates increase as a patient's age advances. Although the majority of patients exhibit different grades of duodenal adenomatosis as they age, only a small proportion (1%-5%) of patients will ultimately develop duodenal carcinoma. Within this context, the aim of the present study was to review the data regarding the epidemiology, classification, genetic features, endoscopic features, carcinogenesis, surveillance and management of duodenal polyps in patients with FAP. PMID- 26265987 TI - Rare gastrointestinal lymphomas: The endoscopic investigation. AB - Gastrointestinal lymphomas represent up to 10% of gastrointestinal malignancies and about one third of non-Hodgkin lymphomas. The most prominent histologies are mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma. However, the gastrointestinal tract can be the site of rarer lymphoma subtypes as a primary or secondary localization. Due to their rarity and the multifaceted histology, an endoscopic classification has not been validated yet. This review aims to analyze the endoscopic presentation of rare gastrointestinal lymphomas from disease diagnosis to follow-up, according to the involved site and lymphoma subtype. Existing, new and emerging endoscopic technologies have been examined. In particular, we investigated the diagnostic, prognostic and follow-up endoscopic features of T-cell and natural killer lymphomas, lymphomatous polyposis and mantle cell lymphoma, follicular lymphoma, plasma cell related disease, gastrointestinal lymphomas in immunodeficiency and Hodgkin's lymphoma of the gastrointestinal tract. Contrarily to more frequent gastrointestinal lymphomas, data about rare lymphomas are mostly extracted from case series and case reports. Due to the data paucity, a synergism between gastroenterologists and hematologists is required in order to better manage the disease. Indeed, clinical and prognostic features are different from nodal and extranodal or the bone marrow (in case of plasma cell disease) counterpart. Therefore, the approach should be based on the knowledge of the peculiar behavior and natural history of disease. PMID- 26265989 TI - Uncommon complications of therapeutic endoscopic ultrasonography: What, why, and how to prevent. AB - There is an increasing role for endoscopic ultrasound (EUS)-guided interventions in the treatment of many conditions. Although it has been shown that these types of interventions are effective and safe, they continue to be considered only as alternative treatments in some situations. This is in part due to the occurrence of complications with these techniques, which can occur even when performed by experienced endosonographers. Although common complications have been described for many procedures, it is also crucial to be aware of uncommon complications. This review describes rare complications that have been reported with several EUS guided interventions. EUS-guided biliary drainage is accepted as an alternative treatment for malignant biliary obstruction. Most of the uncommon complications related to this procedure involve stent malfunction, such as the migration or malposition of stents. Rare complications of EUS-guided pancreatic pseudocyst drainage can result from air embolism and infection. Finally, a range of uncommon complications has been reported for EUS-guided celiac plexus neurolysis, involving neural and vascular injuries that can be fatal. The goal of this review is to identify possible complications and promote an understanding of how they occur in order to increase general awareness of these adverse events with the hope that they can be avoided in the future. PMID- 26265990 TI - New technologies and techniques to improve adenoma detection in colonoscopy. AB - Adenoma detection rate (ADR) is a key component of colonoscopy quality assessment, with a direct link between itself and future mortality from colorectal cancer. There are a number of potential factors, both modifiable and non-modifiable that can impact upon ADR. As methods, understanding and technologies advance, so should our ability to improve ADRs, and thus, reduce colorectal cancer mortality. This article will review new technologies and techniques that improve ADR, both in terms of the endoscopes themselves and adjuncts to current systems. In particular it focuses on effective techniques and behaviours, developments in image enhancement, advancement in endoscope design and developments in accessories that may improve ADR. It also highlights the key role that continued medical education plays in improving the quality of colonoscopy and thus ADR. The review aims to present a balanced summary of the evidence currently available and does not propose to serve as a guideline. PMID- 26265991 TI - Current role of non-anesthesiologist administered propofol sedation in advanced interventional endoscopy. AB - Complex and lengthy endoscopic examinations like endoscopic ultrasonography and/or endoscopic retrograde cholangiopancreatography benefit from deep sedation, due to an enhanced quality of examinations, reduced discomfort and anxiety of patients, as well as increased satisfaction for both the patients and medical personnel. Current guidelines support the use of propofol sedation, which has the same rate of adverse effects as traditional sedation with benzodiazepines and/or opioids, but decreases the procedural and recovery time. Non-anesthesiologist administered propofol sedation has become an option in most of the countries, due to limited anesthesiology resources and the increasing evidence from prospective studies and meta-analyses that the procedure is safe with a similar rate of adverse events with traditional sedation. The advantages include a high quality of endoscopic examination, improved satisfaction for patients and doctors, as well as decreased recovery and discharge time. Despite the advantages of non anesthesiologist administered propofol, there is still a continuous debate related to the successful generalization of the procedures. PMID- 26265992 TI - Endoscopic papillectomy: The limits of the indication, technique and results. AB - In the majority of cases, duodenal papillary tumors are adenomas or adenocarcinomas, but the endoscopy biopsy shows low accuracy to make the correct differentiation. Endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography are important tools for the diagnosis, staging and management of ampullary lesions. Although the endoscopic papillectomy (EP) represent higher risk endoscopic interventions, it has successfully replaced surgical treatment for benign or malignant papillary tumors. The authors review the epidemiology and discuss the current evidence for the use of endoscopic procedures for resection, the selection of the patient and the preventive maneuvers that can minimize the probability of persistent or recurrent lesions and to avoid complications after the procedure. The accurate staging of ampullary tumors is important for selecting patients to EP or surgical treatment. Compared to surgery, EP is associated with lower morbidity and mortality, and seems to be a preferable modality of treatment for small benign ampullary tumors with no intraductal extension. The EP procedure, when performed by an experienced endoscopist, leads to successful eradication in up to 85% of patients with ampullary adenomas. EP is a safe and effective therapy and should be established as the first-line therapy for ampullary adenomas. PMID- 26265993 TI - Gastric polyps: Association with Helicobacter pylori status and the pathology of the surrounding mucosa, a cross sectional study. AB - AIM: To assess the endoscopic characteristics of gastric polyps and their association with Helicobacter pylori (H. pylori) status in a predominantly Hispanic population. METHODS: We conducted a retrospective study of all esophagogastroduodenoscopies performed at our institution. Demographic, endoscopic and histopathological data were reviewed. Categorization of patients into Hispanic and Non-Hispanic was based on self-identification. Patients without resection/biopsy were not included in the analysis. Identification of polyps type was based on histological examination. One way analysis of variance was used to compare continuous variables among different polyp types and Fisher's exact test was used compare categorical variables among polyp types. Unadjusted and adjusted comparisons of demographic and clinical characteristics were performed according to the H. pylori status and polyp type using logistic regressions. RESULTS: Of 7090 patients who had upper endoscopy, 335 patients had gastric polyps (4.7%). Resection or biopsy of gastric polyps was performed in 296 patients (88.4%) with a total of 442 polyps removed or biopsied. Of 296 patients, 87 (29%) had hyperplastic polyps, 82 (28%) had fundic gland polyps and 5 (1.7%) had adenomatous polyps. Hyperplastic polyps were significantly associated with positive H. pylori status compared with fundic gland polyps (OR = 4.621; 95%CI: 1.92-11.13, P = 0.001). Hyperplastic polyps were also found to be significantly associated with portal hypertensive gastropathy compared with fundic gland polyps (OR = 6.903; 95%CI: 1.41-33.93, P = 0.0174). Out of 296 patients, 30 (10.1%) had a follow-up endoscopy with a mean duration of 26 +/- 16.3 mo. Interval development of cancer was not noted in any of the patients during follow up period. CONCLUSION: Gastric hyperplastic polyps were significantly associated with positive H. pylori status and portal hypertensive gastropathy as compared with fundic gland polyps. PMID- 26265994 TI - Glucose control in critical care. AB - Glycemic control among critically-ill patients has been a topic of considerable attention for the past 15 years. An initial focus on the potentially deleterious effects of hyperglycemia led to a series of investigations regarding intensive insulin therapy strategies that targeted tight glycemic control. As knowledge accumulated, the pursuit of tight glycemic control among critically-ill patients came to be seen as counterproductive, and moderate glycemic control came to dominate as the standard practice in intensive care units. In recent years, there has been increased focus on the importance of hypoglycemic episodes, glycemic variability, and premorbid diabetic status as factors that contribute to outcomes among critically-ill patients. This review provides a survey of key studies on glucose control in critical care, and aims to deliver perspective regarding glycemic management among critically-ill patients. PMID- 26265995 TI - Interpretation of cardiovascular outcome trials in type 2 diabetes needs a multiaxial approach. AB - In cardiovascular (CV) diabetology a "one-size fits-all" approach needs caution as vasculopathy and CV manifestations in patients with type 2 diabetes (T2D) with short disease duration are different as compared to those with longer duration. This is of relevance when interpreting results of CV outcome trials as responses to any intervention aimed to reduce CV risk might be different in patients with established vasculopathy as compared to those without, where also the duration of the intervention may play a role. Additionally, the mode-of-action of the intervention and its assumed time to peak CV risk modulation need to be taken into account: an intervention with possibly immediate effects, like on blood pressure or other direct functional dynamic parameters such as endothelial function or renal hemodynamics, could likely provide a meaningful impact on CV outcomes over a shorter time span than interventions that primarily target pathways that work on atherosclerotic processes, organ-remodelling, or vessel integrity. We are now faced with CV outcome results to interpret from a plethora of outcomes trials in T2D, some of which are testing the CV risk modulation predominantly beyond glucose lowering, e.g., as is the case for several trials testing the newer therapy classes di-peptidyl peptidase-4 inhibitors, glucagon like protein-1 receptor analogues and sodium glucose co-transporter-2 inhibitors, and this paper reviews the data that support a call for a multiaxial approach to interpret these results. PMID- 26265996 TI - Aloesin as a medical food ingredient for systemic oxidative stress of diabetes. AB - Diabetes is a chronic disease that requires a long term management where oxidative stress plays a pivotal role in disease progression and intensifying secondary complications. In spite of all the research on diabetes and recent advances in diabetes treatments, the reality is that there is no cure for diabetes and its devastating complications. While currently available anti diabetic therapies are effective in reducing blood glucose level, they are not without associated side effects when they are used for a long term applications. As a result, physicians and patients are inclining more towards to a safer therapy with less serious side effects in the form of medicinal foods and botanical alternatives that are suitable for chronic usage. Aloesin, an Aloe chromone, has previously been formulated with an aloe polysaccharide to give a composition called Loesyn, where it showed significant impact in reducing glycosylated hemoglobin, fasting blood glucose, fructosamine and plasma insulin level in humans. Radical scavenging activities of chromones and polysaccharides from Aloe have also been reported. Here we rationalize the relevance of use of Aloesin alone or in a standardized blend with Aloe polysaccharides, as a potential medical food to manage systemic oxidative stress and/or high blood glucose of diabetes. PMID- 26265997 TI - Limited joint mobility syndrome in diabetes mellitus: A minireview. AB - Limited joint mobility syndrome (LJMS) or diabetic cheiroarthropathy is a long term complication of diabetes mellitus. The diagnosis of LJMS is based on clinical features: progression of painless stiffness of hands and fingers, fixed flexion contractures of the small hand and foot joints, impairment of fine motion and impaired grip strength in the hands. As the syndrome progresses, it can also affect other joints. It is important to properly diagnose such a complication as LJMS. Moreover, it is important to diagnose LJMS because it is known that the presence of LJMS is associated with micro- and macrovascular complications of diabetes. Due to the lack of curative treatment options, the suggested method to prevent or decelerate the development of LJMS is improving or maintaining good glycemic control. Daily stretching excercises of joints aim to prevent or delay progression of joint stiffness, may reduce the risk of inadvertent falls and will add to maintain quality of life. PMID- 26265998 TI - Epigenetic profiles of pre-diabetes transitioning to type 2 diabetes and nephropathy. AB - AIM: To examine DNA methylation profiles in a longitudinal comparison of pre diabetes mellitus (Pre-DM) subjects who transitioned to type 2 diabetes mellitus (T2DM). METHODS: We performed DNA methylation study in bisulphite converted DNA from Pre-DM (n = 11) at baseline and at their transition to T2DM using Illumina Infinium HumanMethylation27 BeadChip, that enables the query of 27578 individual cytosines at CpG loci throughout the genome, which are focused on the promoter regions of 14495 genes. RESULTS: There were 694 CpG sites hypomethylated and 174 CpG sites hypermethylated in progression from Pre-DM to T2DM, representing putative genes involved in glucose and fructose metabolism, inflammation, oxidative and mitochondrial stress, and fatty acid metabolism. These results suggest that this high throughput platform is able to identify hundreds of prospective CpG sites associated with diverse genes that may reflect differences in Pre-DM compared with T2DM. In addition, there were CpG hypomethylation changes associated with a number of genes that may be associated with development of complications of diabetes, such as nephropathy. These hypomethylation changes were observed in all of the subjects. CONCLUSION: These data suggest that some epigenomic changes that may be involved in the progression of diabetes and/or the development of complications may be apparent at the Pre-DM state or during the transition to diabetes. Hypomethylation of a number of genes related to kidney function may be an early marker for developing diabetic nephropathy. PMID- 26266000 TI - Congenital megaurethra in a fetus with Meckel syndrome and in a fetus with female pseudoermanphroditism. The first report of these occurrences. AB - OBJECTIVE: the purpose of this paper is to report the first case of megaurethra in a fetus with Meckel syndrome and in a fetus with femal pseudoermaphroditism. RESULTS: the former case refers to a fetus of 13 weeks gestation with the three following prominent anomalies, observed by transonic scan and confirmed by autopsy: congenital megaurethra, anal atresia, single umbelical artery. The latter case refers to a fetus of 18 weeks gestation. Autopsy confirmed penile malformation and revealed ovaries in the abdomen. The karyotype was 46,XX with normal molecular karytype. The megaurethra was discovered by sonography at 18 weeks gestation. Autopsy confirmed penile malformation and revealed ovaries in the abdomen. The karyotype was 46,XX with normal molecular karyotype (Array-CGH, 1 Mb of resolution). METHODS: transonic scan, autopsy, karyotype, array-CGH. CONCLUSIONS: the first prenatal cases of two genetic syndromes with megaurethra have been reported, concening respectively a fetus with Meckel syndrome and a fetus with femal pseudoermaphroditism. The latter was confirmed by both autopsy and the normal female 46,XX karyotype. PMID- 26265999 TI - Comparison between modified Misgav-Ladach and Pfannenstiel-Kerr techniques for Cesarean section: review of literature. AB - In the last decades cesarean section rates increased in many countries becoming the most performed intraperitoneal surgical procedure. Despite its worldwide spread, a general consensus on the most appropriate technique to use has not yet been reached. The operative technique performed is made chiefly on the basis of the individual experience and preference of operators, the characteristics of patients, timing and urgency of intervention. We compared the two most known and used techniques, modified Misgav-Ladach and traditional Pfannenstiel-Kerr, and analyzed their impact on primary, short- and long-term outcomes and outcome related to health service use. PMID- 26266001 TI - Tubal primary metastatic choriocarcinoma coexistent with a viable early pregnancy: a case report. AB - INTRODUCTION: fallopian tube choriocarcinoma coexistent with viable intrauterine pregnancy is an extremely rare condition. CASE REPORT: we present the first case reported in literature of tubal choriocarcinoma coexistent with viable intrauterine pregnancy detected at early gestational age (20 weeks) and successfully managed by seriate monitoring of maternal and fetal health status until 31 weeks, then treated by cesarean section followed by etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA-CO) chemotherapy protocol. CONCLUSIONS: the outcome was favorable for both the mother and her fetus. PMID- 26266003 TI - Comparative study of aCGH and Next Generation Sequencing (NGS) for chromosomal microdeletion and microduplication screening. AB - BACKGROUND: prenatal genetic diagnosis of rare disorders is undergoing in recent years a significant enhancement through the application of methods of massive parallel sequencing. Despite the quantity and quality of the data produced, just few analytical tools and software have been developed in order to identify structural and numerical chromosomal anomalies through NGS, mostly not compatible with benchtop NGS platform and routine clinical diagnosis. METHODS: we developed technical, bioinformatic, interpretive and validation pipelines for Next Generation Sequencing to identify SNPs, indels, aneuploidies, and CNVs (Copy Number Variations). RESULTS: we show a new targeted resequencing approach applied to prenatal diagnosis. For sample processing we used an enrichment method for 4,813 genes library preparation; after sequencing our bioinformatic pipelines allowed both SNPs analysis for approximately thirty diseases or diseases family involved in fetus development and numerical chromosomal anomalies screening. CONCLUSIONS: results obtained are compatible with those obtained through the gold standard technique, aCGH array, moreover allowing identification of genes involved in chromosome deletions or duplications and exclusion of point mutation on allele not affected by chromosome aberrations. PMID- 26266002 TI - Retrospective study evaluating the performance of a first-trimester combined screening for trisomy 21 in an Italian unselected population. AB - OBJECTIVES: to assess the performance of a combined first-trimester screening for trisomy 21 in an unselected Italian population referred to a specialized private center for prenatal medicine. METHODS: a retrospective validation of first trimester screening algorithms [risk calculation based on maternal age and nuchal translucency (NT) alone, maternal age and serum parameters (free beta-hCG and PAPP-A) alone and a combination of both] for fetal aneuploidies evaluated in an unselected Italian population at Artemisia Fetal-Maternal Medical Centre in Rome. All measurements were performed between 11(+0) and 13(+6) weeks of gestation, between April 2007 and December 2008. RESULTS: of 3,610 single fetuses included in the study, we had a complete follow-up on 2,984. Fourteen of 17 cases of trisomy 21 were detected when a cut-off of 1:300 was applied [detection rate (DR) 82.4%, 95% confidence interval (CI) 64.2-100; false-positive rate (FPR) 4.7%, 95% CI 3.9-5.4; false-negative rate (FNR) 17.6%, 95% CI 0-35.8%]. CONCLUSION: in our study population the detection rate for trisomy 21, using the combined risk calculation based on maternal age, fetal NT, maternal PAPP-A and free beta-hCG levels, was superior to the application of either parameter alone. The algorithm has been validated for first trimester screening in the Italian population. PMID- 26266004 TI - Antenatal diagnosis of Seckel Syndrome: a rare case report. AB - INTRODUCTION: Seckel Syndrome is a rare autosomal recessive disorder characterized by dwarfism, microcephaly and the absence of visceral malformations. CASE REPORT: we observed sonographic features of a Seckel Syndrome, in a patient during the 24th week of pregnancy. Her family history was negative for malformation and chromosomal disorders. The diagnosis was later confirmed by molecular tests. CONCLUSION: diagnosis should be made only by expert operators. Karyotype analysis is essential to confirm the diagnosis. PMID- 26266005 TI - Adenocarcinoma of Small Bowel. AB - Small bowel cancer is one of the rarest cancers in the gastrointestinal tract. The diagnosis is usually late and most patients presented with the advanced stage. Because of this rarity, there is limited data when making decisions for treatment and biological behavior. Most forms of the cancer occur in the duodenum with surgery being the treatment of choice if the cancer is operable. Chemotherapy has an accepted role in duodenal cancer, with the best form being regimen, which yields the best result in combination with capecitabin and oxaliplatin. Our case patient was present with liver metastasis and a huge mass in her first duodenal region so we were required to use chemotherapy and radiotherapy. Like other duodenal cancers, the metastasis decreased her survival and she died about 13 months after diagnosis. PMID- 26266006 TI - Chronic Long Standing Shoulder Pain, Caused by Glomus Tumor. AB - Chronic shoulder pain can be caused by muscle, bone and joint inflammatory and tumoral lesions; however, chronic shoulder pain secondary to benign vascular tumor called glomus tumor is an extremely rare occurrence. To the best of our knowledge less than 15 cases of chronic shoulder pain have been reported secondary to glomus tumor. Herein we report our experience with a young lady who presented with chronic shoulder pain which turned out to be caused by a soft tissue glomus tumor. This case has also been unique because if its large size (about 5 cm in greatest diameter). PMID- 26266007 TI - Large Malignant Phyllodes Tumor of the Breast with Metastases to the Lungs. AB - Phyllodes tumors of the breast account for less than 0.5% of breast cancers and present most commonly in women 45 to 49 years old. The importance in managing fibroepithelial lesions lies in distinguishing fibroadenomas, which are benign, from phyllodes tumors, which can be malignant and require complete surgical excision. We report the case of a 56-year-old female who presented with a rapidly enlarging mass in her right breast 18 cm in maximum dimension that completely effaced the breast and distorted the nipple. The patient underwent a successful total mastectomy after core biopsy revealed a diagnosis of phyllodes tumor. Surgical resection is the primary treatment modality; neoadjuvant and adjuvant therapies remain controversial. Here, we report the case of a large malignant phyllodes tumor metastatic to the lungs, review the literature, and discuss diagnostic modalities and adjunct nonsurgical therapies. PMID- 26266008 TI - Amelanotic Melanoma Presenting with Plasmacytoid Morphology and BRAF V600 Mutation. AB - Plasmacytoid melanoma is an unusual variant of malignant melanoma. The plasmacytoid morphology can be found in a variety of other malignancies including carcinomas, plasma cell neoplasms, lymphoproliferative disorders, and sarcomas. The authors report a rare case of plasmacytoid amelanotic malignant melanoma in a 78-year-old man presenting with an enlarging palpable, erythematous mass on his left posterior shoulder. A fine needle aspirate showed atypical findings with single amelanotic cells with high nuclear to cytoplasmic ratio, mono- and multi nucleation with prominent nucleoli and intranuclear inclusions. Review of the excision and immunohistochemical analysis revealed the malignant plasmacytoid cells stained with vimentin, S-100, HMB-45, and other staining patterns consistent with melanoma. Initial evaluation was negative for other sites of disease. However, 4 months later, the patient was noted to have metastatic disease to his lungs and liver. Given that the tumor was noted to be BRAF V600R mutated, the patient was started on single agent dabrafenib. The plasmacytoid morphology can be found in a variety of malignancies. Melanoma should be considered in the differential diagnosis of any malignancy presenting with plasmacytoid features. PMID- 26266009 TI - CD10 Positive Recurrent Undifferentiated Mammary Sarcoma in a Young Female: A Rare Case Report with Brief Review of Literature. AB - Undifferentiated mammary sarcoma is extremely rare and the diagnosis is made only after exclusion of metaplastic carcinomas and malignant phyllodes tumor. Mammary sarcomas mostly display specified entities like liposarcomas or angiosarcomas. A 18-year-old female presented in 2010 with a right breast lump for which lumpectomy was done and on histopathological examination benign phyllodes tumor was diagnosed. In 2011, there was a recurrence at site of excised margin and on fine needle aspiration (FNA) the diagnosis of benign breast disease was made; a small biopsy was received for which diagnosis of myoepithelial lesion was given. Then, the whole mass was excised, but histopathological examination report could not be followed up. In 2013, she again presented with a mass arising from the previously excised margin; on FNA, it was diagnosed as malignant sarcomatous lesion. Microscopy showed spindle shaped cells in diffuse and fascicular pattern with plump ovoid nuclei; coarse chromatin and eosinophilic cytoplasm were seen. Few round to ovoid cells with eccentric nuclei and showing bi- or multi nucleation were present. Large area of necrosis and hemorrhage was present, too. No breast glands were found. Later on, diagnosis was confirmed on immunohistochemical examination. The case was considered worth due to the young age of the patient and lack of differentiation of the lesion in any specific type of sarcoma and CD10 positivity. PMID- 26266010 TI - Gastric Metastasis of Triple Negative Invasive Lobular Carcinoma. AB - Invasive lobular carcinomas are the second most common type (5% to 15%) of invasive breast carcinomas. The most frequent sites of breast cancer metastasis are the local and distant lymph nodes, brain, lung, liver, and bones; metastasis to the gastrointestinal system, especially to the stomach, is rare. When a mass is detected in an unusual place in a patient with invasive lobular carcinoma, it should be kept in mind that such a mass may be either a second primary carcinoma or the metastasis of an invasive lobular carcinoma. In this report, we present a case of gastric metastasis from triple-negative invasive lobular breast cancer. It is important to make an accurate diagnosis by distinguishing gastric metastasis from breast cancer in order to select the best initial treatment for systemic diseases of breast cancer. Considering our case, healthcare professionals should take into account that cases with invasive lobular breast cancer may experience unusual metastases. PMID- 26266011 TI - Breast Metastasis from Medullary Thyroid Carcinoma in a Male Patient: Case Report and Review of the Literature. AB - Medullary thyroid carcinoma (MTC) is a rare malignancy that may metastasize to liver, lungs and bones. Breast is an unusual metastatic site for MTC and only 20 female cases have been reported in the literature. We present a male patient in whom histological examination and immunohistochemistry of a breast mass were indicative of breast metastasis from MTC. A 67-year-old man with recent diagnosis of MTC and metastases to cervical and upper mediastinum lymph nodes was referred to our department for further treatment. At first evaluation, diagnostic imaging techniques showed lung and bone metastases and three months later the presence of liver metastases. Due to the extension of the disease, treatment with vandetanib was decided, but serious adverse events led to its interruption after two weeks. During follow-up, patient developed a painful swelling in the right breast. Ultrasound and mammography showed the presence of multiple masses to the right breast suspicious for malignancy. Core needle biopsy and histological examination of the specimen confirmed the presence of metastatic MTC. Palliative external beam irradiation was used to relieve local pain and, after one month, the patient died. Consequently, breast masses should be cautiously evaluated, mainly in the presence of a known primary malignancy. Histological and/or cytopathological examination are requisite diagnostic tools, while external beam irradiation and tyrosine kinase inhibitors may be used as palliative therapies in the concurrent presence of breast metastases from MTC. PMID- 26266012 TI - Large Mid-Esophageal Granular Cell Tumor: Benign Versus Malignant. AB - Granular cell tumors are rare soft tissue neoplasms, among which only 2% are malignant, arising from nervous tissue. Here we present a case of a large esophageal granular cell tumor with benign histopathological features which metastasized to the liver, but showing on positron emission tomography computerized tomography standardized uptake value suggestive of a benign lesion. PMID- 26266013 TI - Fine Needle Aspiration Cytology of Chondroid Tenosynovial Giant Cell Tumor of the Hand. AB - Giant cell tumor (GCT) of tendon sheath is a localized form of tenosynovial GCT, which preferentially affects the joints of hands and feet. Chondroid metaplasia is a rare phenomenon in tenosynovial GCT either in localized or diffuse types. The current case investigates the cytological and histopathological features of chondroid GCT of tendon sheath in a 22-year-old female presenting with wrist swelling. PMID- 26266014 TI - Pediatric Metastatic Odontogenic Ghost Cell Carcinoma: A Multimodal Treatment Approach. AB - Odontogenic ghost cell carcinoma (OGCC) is a rare and aggressive tumor wherein optimal treatment remains uncertain. We report the first pediatric metastatic OGCC case treated with multimodal therapy: surgery, adjuvant chemoradiation, and adjuvant immunotherapy. Adjuvant therapy was utilized due to locally advanced disease with pathologic features indicative of high recurrence risk. This multimodal approach was modeled after management of primary head and neck cancer, where adjuvant chemoradiation and immunotherapy are associated with improved outcomes. Our patient is alive and disease free at 14 months indicating a potentially positive role for multimodal therapy in the management of OGCC. PMID- 26266015 TI - An Unusual Presentation of Cystic Nephroma in an Adult Man. AB - Cystic nephroma (CN) is an uncommon, benign lesion of the kidney, whose clinical presentation is nonspecific with symptoms such as flack pain, hematuria and urinary tract infection. There are two peaks in the incidence of the tumor, with a bimodal distribution presenting in children between three months and two years, and in adults over 30-years of age. We report a case of CN in the middle part of the left kidney in a 66-year-old male that presented with a singular unilocular, well-circumscribed cyst containing numerous calcifications on the walls and with unremarkable thin or relatively thicker septa from the border with the renal parenchyma, but no solid components. Laparoscopic nephrectomy was performed. Images, histopathological and immunohistochemical features, that are potentially useful for refining this lesion, are discussed. PMID- 26266016 TI - Digital Papillary Adenocarcinoma: Presentation, Natural History and Management. AB - Digital papillary adenocarcinoma (DPA) is a rare malignant tumor of the sweat glands that often presents as a solitary painless mass on the digits of the hands or feet. We present a rare case of DPA on the ankle in a 54 year-old African American man. Although the most common location for digital papillary adenocarcinoma is on the hands and feet, it can present in other locations. Treatment modalities and concerns such as the level of margin resection, degree of negative margins, and the need for a sentinel lymph node biopsy might be different if the tumor is encountered in locations other than the digits. In the following manuscript, we discuss the natural history of this rare tumor including a review of the current literature with emphasis on documented treatment strategies as well as the approach in treating patients with a unique presentation. PMID- 26266017 TI - High Grade Leiomyosarcoma Mimicking a Recurrent Angiomyxoma in the Perineum. AB - Perineal leiomyosarcoma is an extremely rare and aggressive cancer with a high metastatic potential and no defined standard treatment. There are only a few (six) reported cases in the literature. We report the case of a 67-year-old woman with a perineal leiomyosarcoma arising at the same site of a previously resected superficial angiomyxoma. Initially, she was treated for a presumptive recurrence of angiomyxoma. As she did not respond to medical therapy, she underwent repeat surgical excision. Pathology revealed a high grade leiomyosarcoma, histologically strikingly distinct from the initial diagnosis. She received adjuvant local radiation therapy, and remains without evidence of recurrent disease 36 months after completion of all therapy. This is the first reported case of a high grade perineal leiomyosarcoma originating at the same site as a resected benign superficial angiomyxoma. Our case emphasizes the necessity of a prompt histological diagnosis in cases of presumed recurrent perineal angiomyxoma. PMID- 26266018 TI - Trabecular Variant of Juvenile Aggressive Ossifying Fibroma. AB - Juvenile aggressive ossifying fibroma (JAOF) is an uncommon benign lesion which is distinctly aggressive in behavior with high tendency for recurrence. It appears in early age and in 79% of patients is diagnosed before 15. It has two histological variants: psammomatoid and trabecular, with the latter being less common with a stronger tendency to recur. In this article, we present a case of trabecular JAOF, in which treatment could not be given despite the availability of all requisites for surgery and good financial status, due to parental indifference and negligence. PMID- 26266019 TI - Clinical Activity of Pazopanib in Metastatic Extraosseous Ewing Sarcoma. AB - We report a response to pazopanib in a 69-year-old man with heavily pre-treated metastatic extraosseous Ewing sarcoma in addition to molecular profiling of his tumor. To our knowledge, this case is the earliest to demonstrate activity of an oral multi-targeted kinase inhibitor in Ewing sarcoma. This case provides rationale for adding a Ewing sarcoma arm to SARC024, a phase II study of regorafenib, another multi-targeted kinase inhibitor, in patients with liposarcoma, osteosarcoma and Ewing and Ewing-like sarcomas (NCT02048371). This national multi-institutional study is ongoing. PMID- 26266020 TI - Socio-Cultural Context and Feelings of Hatred and Revenge in War Veterans with Post-Traumatic Stress Disorder 15 Years after War in Kosovo. AB - We aimed to assess, in socio-cultural context, the level of hatred and revenge in war veterans with post-traumatic stress disorder (PTSD). The sampling frame consisted of 215 Kosova War veterans, randomly selected. The Harvard Trauma Questionnaire was used to assess the prevalence of PTSD and Manchester Short Assessment of Life was used to assess social satisfactions. The participants were asked to declare the strength of feelings of hatred and revenge in the four preceding weeks by using four items scale: not at all, a little bit/sometimes, a lot and extremely. Willingness for action of veterans was assessed using three item scale: yes, no or maybe. A probability level of 0.05 was adopted to be considered as statistically significant for differences among groups. DSM-IV-TR criteria for PTSD (very similar to DSM-V) were met by 52.6% of veterans; the data have confirmed existence of thoughts and fantasies of revenge against opposing forces by 42.8% veterans; at the same level 42.8% manifested feelings of hatred. Fantasies of taking revenge a lot was recorded by 19.5% and extremely by 1.4% of veterans, while hateful thoughts at level a lot were likely expressed by 22.3% and extreme by 2.8% of veterans. It is important to note that 84.7% were confident to act based on their beliefs. Social-economic and cultural factors have played major role in the understanding of psychological problems of traumatized individuals with a direct impact on their ability to function socially. This study has confirmed the urgent need for the establishment of psychological rehabilitation programs as well as programs for the social and economic rehabilitation of War Veterans. PMID- 26266021 TI - Diagnostic Stability of Acute and Transient Psychotic Disorders in Developing Country Settings: An Overview. AB - Acute and transient psychotic disorders (ATPD), introduced in the International Classification of Diseases (ICD-10) diagnostic system in 1992, are not receiving much attention in developing countries. Therefore, the main objective of this article is to review the literature related to the diagnostic stability of ATPD in developing countries. A PubMed search was conducted to review the studies concerned with this issue in the context of developing countries, as diagnostic stability is more of a direct test of validity of psychiatric diagnoses. Four publications were found. According to the literature search, the stability percentage of the ICD-10 ATPD diagnosis is 63-100%. The diagnostic shift is more commonly either towards bipolar disorder or schizophrenia, if any. Shorter duration of illness (<1 month) and abrupt onset (<48 hours) predict a stable diagnosis of ATPD. Based on available evidence, the diagnosis of ATPD appears to be relatively stable in developing countries. However, it is difficult to make a definitive conclusion, as there is a substantial lack of literature in developing country settings. PMID- 26266022 TI - The Effects of Phosphatidylserine and Omega-3 Fatty Acid-Containing Supplement on Late Life Depression. AB - Late life depression is often associated with a poor response to antidepressants; therefore an alternative strategy for therapy is required. Although several studies have reported that phosphatidylserine (PS) may be effective for late life depression and that omega-3 fatty acids DHA and EPA have also proven beneficial for many higher mental functions, including depression, no concrete conclusion has been reached. This study was performed to clarify the effect of PS and omega 3 fatty acid-containing supplement for late life depression by not only clinical evaluation but also salivary cortisol levels. Eighteen elderly subjects with major depression were selected for the study. In all, insufficient improvement had been obtained by antidepressant therapy for at least 6 months. The exclusion criteria from prior brain magnetic resonance images (MRI) included the presence of structural MRI findings compatible with stroke or other gross brain lesions or malformations, but not white matter hypersensitivities. They took a supplement containing PS 100 mg, DHA 119 mg and EPA 70 mg three times a day for 12 weeks. The effects of the supplement were assessed using the 17-item Hamilton depression scale (HAM-D17) and the basal levels and circadian rhythm of salivary cortisol. The study adopted them as indices because: salivary cortisol levels are high in patients with depression, their circadian rhythm related to salivary cortisol is often irregular, and these symptoms are alleviated as depression improves. The mean HAM-D17 in all subjects taking the supplement was significantly improved after 12 weeks of taking the supplement. These subjects were divided into 10 non responders and 8 responders. The basal levels and circadian rhythm of salivary cortisol were normalized in the responders while not in non-responders. PS and omega-3 fatty acids, or other elements of the supplement, may be effective for late life depression, associated with the correction of basal levels and circadian rhythm of salivary cortisol. PMID- 26266023 TI - Balancing Life and Medical School. PMID- 26266024 TI - The Change of Music Preferences Following the Onset of a Mental Disorder. AB - A psychiatric population (n=123) was examined on how music preferences had changed after the onset of a mental disorder. Most patients did not change their previous music preference; this group of patients considered music helpful for their mental state, showed more attractivity and enforcement as personality traits and used music more for emotion modulation. Patients who experienced a preference shift reported that music had impaired them during the time of illness; these patients showed less ego-strength, less confidence and less enforcement and used music less for arousal modulation. A third subgroup stopped listening to music completely after the onset of the mental disorder; these patients attribute less importance to music and also reported that music had impaired their mental state. They showed more ego-strength and used music less for emotion modulation. The results suggest that the use of music in everyday life can be helpful as an emotion modulation strategy. However, some patients might need instructions on how to use music in a functional way and not a dysfunctional one. Psychiatrists and psychotherapists as well as music therapists should be aware of emotion modulation strategies, subjective valence of music and personality traits of their patients. Due to the ubiquity of music, psychoeducative instructions on how to use music in everyday life plays an increasing role in the treatment of mental illness. PMID- 26266025 TI - Vagal Nerve Stimulation for the Treatment of Autism. PMID- 26266026 TI - Psychopathology and Urine Toxicology in Methadone Patients. AB - Several studies reported high rates of psychiatric commorbidity among methadone patients. We examined the relationships of measures of psychopathology to outcomes of screening urine tests for cocaine, opiates, and benzodiazepines in a sample of 56 methadone patients. They also completed the Symptom Check List-90 Revised (SCL-90-R). The highest scales in the SCL-90-R profile of our patients were those indicating somatic discomfort, anger, phobic anxiety, paranoid ideation, and also obsessive-compulsive disorder symptoms (scores above the 39(th) percentile). The only significant correlations between urine tests and SCL 90-R psychopathology were those involving benzodiazepines: patients with urine tests positive for benzodiazepines had lower social self-confidence (r=0.48), were more obsessive-compulsive (r=0.44), reported a higher level of anger (r=0.41), of phobic tendencies (r=40), of anxiety (r=0.39), and of paranoid tendencies (r=0.38), and also reported more frequent psychotic symptoms (r=0.43). PMID- 26266027 TI - Olanzapine-Induced Neutropenia. AB - Olanzapine-induced neutropenia is a rare adverse effect that is currently poorly described in literature. Although neutropenia is a known adverse effect of clozapine, it has been associated with the use of other antipsychotic medications like olanzapine. This case report describes and reviews a case of olanzapine induced neutropenia in a schizophrenic patient. Although the mechanism of antipsychotic-induced neutropenia is still debated, this report attempts to discuss current theories as well as supply evidence in literature of this rare but potentially dangerous adverse effect. PMID- 26266028 TI - Musical Hallucinations in Schizophrenia. PMID- 26266029 TI - Coping Strategies and Locus of Control in Childhood Leukemia: A Multi-Center Research. AB - Acute lymphoblastic leukemia (ALL) is a very distressing experience for children and requires a special effort of adjustment. Therefore, it seems to be crucial to explore coping resources for the experienced risk condition. In this sense, the study focuses on coping strategies and locus of control in children with ALL during the treatment phase, and on their possible relation. The correlation between children and maternal coping strategies is also investigated. The participants involved were an experimental group of 40 children with ALL and their mothers, and 30 healthy children as the control group. The tools used were: the Child Behavioral Style Scale and the Monitor-Blunter Style Scale to assess the coping strategies of children and mothers; the locus of Control Scale for Children to analyze the children's perception of controlling the events. Both children with ALL and their mothers resorted to monitoring coping strategies with a statistically significant rate of occurrence (children: M=17.8, SD=3.8; mothers: M=10.48, SD=3.4). The data concerning the locus of control show this tendency towards internal causes (M=53.1, SD=4.7). There were statistically significant correlations between monitoring coping strategies and external locus of control (r=0.400, P<0.05). The results gained from the control group are almost equivalent. The outcomes show several interesting resources of the psychological functioning of children as well as of their mothers. PMID- 26266030 TI - Risk Factors for Intestinal Obstruction After Ladd Procedure. AB - Intestinal obstruction is a common complication after Ladd procedure. Ninety three cases who had undergone the Ladd procedure between 1977 and 2013 treated at our own institution were retrospectively reviewed to identify the causes and risk factors for intestinal obstruction. The Ladd procedure has been performed without any intestinal fixing. Of the 87 cases who survived to discharge, intestinal obstruction was observed in 22 (25.3%). Among the cases with intestinal obstruction, 13 (59.1%) showed intestinal ischemia at the initial operation; this incidence was notably high, although it is low when only those cases with another concurrent surgical digestive disease are considered. All cases of intestinal obstruction were caused not by recurrent volvulus, but by adhesion between the intestine and the mesentery. Intestinal fixing is not required to prevent recurrent volvulus, but it is important to achieve adequate widening of the mesenteric base. The risk of intestinal obstruction after the Ladd procedure, on the other hand, is high. Moreover, patients with intestinal ischemia have an increased risk of intestinal obstruction. PMID- 26266031 TI - Neonatal Sweet's Syndrome Associated with Rectovestibular Fistula with Normal Anus. AB - Sweet's syndrome, characterized by fever and a painful erythematous rash with a dermal neutrophilic infiltrate, develops primarily due to paraneoplastic phenomena in adults. Sweet's syndrome is very rare in neonates. We report a Japanese female neonate (age <2 months), who developed Sweet's syndrome with episodes of perineal infection in association with congenital rectovestibular fistula with normal anus. Sweet's syndrome was diagnosed basing on clinical features and histopathology of biopsied skin tissues. Rectovestibular fistula was confirmed after the signs of inflammation subsided and the rash disappeared. In the literature, we found another case of neonatal Sweet's syndrome associated with rectovestibular fistula in a Japanese female neonate. The perineal region should be screened for anomalies following diagnosis of Sweet's syndrome in neonates. PMID- 26266032 TI - Acute Disseminated Encephalomyelitis After Plasmodium Vivax Infection: Case Report and Review of Literature. AB - Acute demyelinating encephalomyelitis (ADEM) usually occurs after viral infections or vaccination. Its occurrence after Plasmodium vivax infection is extremely uncommon. We report the case of an 8-year-old girl who had choreo athetoid movements and ataxia after recovery from P.vivax infection. Diagnosis of ADEM was made on the basis of magnetic resonance imaging findings. The child responded to corticosteroids with complete neurological recovery. PMID- 26266033 TI - Paternal and Maternal Transition to Parenthood: The Risk of Postpartum Depression and Parenting Stress. AB - Transition to parenthood represents an important life event increasing vulnerability to psychological disorders. Postpartum depression and parenting distress are the most common psychological disturbances and a growing scientific evidence suggests that both mothers and fathers are involved in this developmental crisis. This paper aims to explore maternal and paternal experience of transition to parenthood in terms of parenting distress and risk of postpartum depression. Seventy-five couples of first-time parents were invited to compile the Edinburgh Postnatal Depression Scale and the Parenting Stress Index-Short Form in the first month of children life. Study sample reported very high levels of parenting distress and a risk of postpartum depression in 20.8% of mothers and 5.7% of fathers. No significant correlation between parenting distress and the risk of postpartum depression emerged, both in mothers than in fathers group while maternal distress levels are related to paternal one. The first month after partum represents a critical phase of parents life and it could be considered a developmental crisis characterized by anxiety, stress and mood alterations that could have important repercussions on the child psycho-physical development. PMID- 26266034 TI - A Novel Noonan Syndrome RAF1 Mutation: Lethal Course in a Preterm Infant. AB - Noonan syndrome is a relatively common and heterogeneous genetic disorder, associated with congenital heart defect in about 50% of the cases. If the defect is not severe, life expectancy is normal. We report a case of Noonan syndrome in a preterm infant with hypertrophic cardiomyopathy and lethal outcome associated to acute respiratory distress syndrome caused by Adenovirus pneumonia. A novel mutation in the RAF1 gene was identified: c.782C>G (p.Pro261Arg) in heterozygosity, not described previously in the literature. Consequently, the common clinical course in this mutation and its respective contribution to the early fatal outcome is unknown. No conclusion can be established regarding genotype/phenotype correlation. PMID- 26266035 TI - Reducing income-related inequalities in care and health: insights from Israel. AB - Amir Shmueli assessed income-related disparities in healthcare and health in Israel, extending earlier studies that focused primarily on education, ethnic or geographic differences. The new analysis finds that the poor are more likely to suffer from an array of chronic conditions, despite higher use of primary care and hospital services. The author suggests that lower use of preventive care, patient behaviors, and lack of adherence to physician recommendations likely contribute to the persistence of health disparities. However, the poor are more likely to work at jobs and live in neighborhoods or housing that put their health at risk. Policies will thus likely need to look beyond medical care to broader social services and workplace issues if the goal is to reduce disparities in disability and heart, lung, mental health and other chronic conditions. If Israeli databases include work and community attributes, it would be useful to include such information to enrich the baseline analysis and to assess the relative efficacy of Ministry of Health and sickness funds initiatives aimed at reducing health disparities. PMID- 26266036 TI - GLP1 and glucagon co-secreting pancreatic neuroendocrine tumor presenting as hypoglycemia after gastric bypass. AB - Post-prandial hypoglycemia is frequently found after bariatric surgery. Although rare, pancreatic neuroendocrine tumors (pNET), which occasionally are mixed hormone secreting, can lead to atypical clinical manifestations, including reactive hypoglycemia. Two years after gastric bypass surgery for the treatment of severe obesity, a 54-year-old female with previous type 2 diabetes, developed post-prandial sweating, fainting and hypoglycemic episodes, which eventually led to the finding by ultrasound of a 1.8-cm solid mass in the pancreatic head. The 72-h fast test and the plasma chromogranin A levels were normal but octreotide scintigraphy showed a single focus of abnormal radiotracer uptake at the site of the nodule. There were no other clinical signs of hormone secreting pNET and gastrointestinal hormone measurements were not performed. The patient underwent surgical enucleation with complete remission of the hypoglycemic episodes. Histopathology revealed a well-differentiated neuroendocrine carcinoma with low grade malignancy with positive chromogranin A and glucagon immunostaining. An extract of the resected tumor contained a high concentration of glucagon (26.707 pmol/g tissue), in addition to traces of GLP1 (471 pmol/g), insulin (139 pmol/g) and somatostatin (23 pmol/g). This is the first report of a GLP1 and glucagon co secreting pNET presenting as hypoglycemia after gastric bypass surgery. Although pNET are rare, they should be considered in the differential diagnosis of the clinical approach to the post-bariatric surgery hypoglycemia patient. LEARNING POINTS: pNETs can be multihormonal-secreting, leading to atypical clinical manifestations.Reactive hypoglycemic episodes are frequent after gastric bypass.pNETs should be considered in the differential diagnosis of hypoglycemia after bariatric surgery. PMID- 26266037 TI - Determination of toxic (Pb, Cd) and essential (Zn, Mn) metals in canned tuna fish produced in Iran. AB - BACKGROUND: Metal pollution of waterways directly affects human health and can impact the food chain. Seafood living in polluted water can accumulate trace metals. The purpose of this study was to analyze the toxic metals Pb and Cd and the dietary essential metals Zn and Mn in 120 cans of tuna species from four different brands processed in Iran and purchased in 2012. RESULTS: The mean level of metals for each brands of canned fish obtained in mg/kg were as follows: yellowfin tuna (Pb: 0.19 +/- 0.015, Zn: 5.77 +/- 4.17, Mn: 0.08 +/- 0.07, Cd: 0.15 +/- 0.12), Kilka (Pb: 0.95 +/- 0.88, Zn: 30.47 +/- 29.82, Mn: 1.01 +/- 0.73, Cd: 0.07 +/- 0.05), Kawakawa (Pb: 0.28 +/- 0.23, Zn: 6.77 +/- 5.21, Mn: 0.17 +/- 0.12, Cd: 0.12 +/- 0.09), longtail tuna (Pb: 1.59 +/- 1.56, Zn: 7.44 +/- 6.11, Mn: 0.04 +/- 0.03, Cd: 0.06 +/- 0.04). Pb, Zn and Cd levels were generally higher than the FAO/WHO permissible limits (Pb: 0.50 mg/kg, Zn: 50.0 mg/kg and Cd: 0.50 mg/kg) and the European Union acceptable dietary limits. CONCLUSIONS: Based on the United States Environmental Protection Agency health criteria, there is no health risk associated with Mn concentration in the samples analyzed. The limits of detection of the method for Pb, Zn, Mn and Cd in mg/kg were 0.01, 0.5, 0.01 and 0.01, respectively. The result of the one-way analysis of variance suggested significant variations (p < 0.05) in the concentration of the metals in the different types of canned fish with the following being outside of compliance levels. PMID- 26266038 TI - Strategic internal covalent cross-linking of TNF produces a stable TNF trimer with improved TNFR2 signaling. AB - BACKGROUND: Soluble TNF superfamily (TNFSF) ligands are less stable and less active than their transmembrane (tm) analogues. This is a problem for the therapeutic use of recombinant TNFSF ligands in diverse diseases including cancer and autoimmunity. Creating TNFSF ligand analogues with improved targeting of their respective receptors is important for research and therapeutic purposes. FINDINGS: Covalent internal cross-linking of TNF monomers by double mutations, S95C/G148C, results in stable trimers with improved TNFR2 function. The resulting mutein induced the selective death of autoreactive CD8 T cells in type-1 diabetic patients and demonstrates targeted proliferation and expansion of human CD4 Tregs. CONCLUSIONS: Stable TNF trimers, created by internal covalent cross linking, show improved signaling. The high structural homology within the TNF superfamily provides an opportunity to extend internal cross-linking to other TNF superfamily proteins to produce active trimers with improved stability and receptor signaling, and with potential applications for cancer, autoimmunity, infections, and transplantation. PMID- 26266039 TI - Implications of miscoding urological procedures in an era of financial austerity 'Every Penny Counts'. AB - OBJECTIVES: The study aimed to find out any inaccuracy in coding of elective urology procedures and associated financial implications. DESIGN: Retrospective audit and re-audit. SETTINGS: Introduction of payment by results was introduced in the NHS in England in 2002. This meant that hospitals are paid on individual patient basis according to their human resource group (HRG) rather than a block contract. Current coding system uses office of population census and surveys classification. These along with other variables determine the final human resource group code defining final payment. PARTICIPANTS: None. MAIN OUTCOME MEASURE: Retrospective analysis of coding for all inpatient urological procedures was performed over a period of two months. All documented Office of Population Census and Surveys codes were recorded and reviewed by urology trainee along with the head of professional coders. As a result of first analysis the deficiencies were identified and revised Office of Population Census and Surveys codes were used to generate the final human resource group codes. After six months a re audit was done. RESULTS: In the initial study, 121 cases were reviewed. Twenty per cent of these cases were miscoded. The revised Office of Population Census and Surveys codes led to change of final human resource group code and hence recovery of a payment of L10,716. Analysis after six months showed a considerable improvement with incorrect coding reduced to 11%. CONCLUSION: Our findings highlight potential discrepancies in coding which can lead to significant financial loss. It is important that surgeons involve and train the coding department so that coding errors can be avoided. This will put us in better position to deal with Nicolson Challenge. PMID- 26266040 TI - A case of HIV ulcer. AB - HIV-associated ulcers must be distinguished from idiopathic anal fissures in HIV positive patients and from other sexually transmitted diseases that cause anogenital ulcers as the treatments differ. PMID- 26266041 TI - Orf - an orphan disease? AB - Human orf should be considered based on a typical presentation with erythematous papule/nodule to avoid unnecessary over-treatment. PMID- 26266042 TI - Chronic kidney disease in congenital heart disease patients: a narrative review of evidence. AB - PURPOSE OF REVIEW: Patients with congenital heart disease have a number of risk factors for the development of chronic kidney disease (CKD). It is well known that CKD has a large negative impact on health outcomes. It is important therefore to consider that patients with congenital heart disease represent a population in whom long-term primary and secondary prevention strategies to reduce CKD occurrence and progression could be instituted and significantly change outcomes. There are currently no clear guidelines for clinicians in terms of renal assessment in the long-term follow up of patients with congenital heart disease. Consolidation of knowledge is critical for generating such guidelines, and hence is the purpose of this view. This review will summarize current knowledge related to CKD in patients with congenital heart disease, to highlight important work that has been done to date and set the stage for further investigation, development of prevention strategies, and re-evaluation of appropriate renal follow-up in patients with congenital heart disease. SOURCES OF INFORMATION: The literature search was conducted using PubMed and Google Scholar. FINDINGS: Current epidemiological evidence suggests that CKD occurs in patients with congenital heart disease at a higher frequency than the general population and is detectable early in follow-up (i.e. during childhood). Best evidence suggests that approximately 30 to 50 % of adult patients with congenital heart disease have significantly impaired renal function. The risk of CKD is higher with cyanotic congenital heart disease but it is also present with non-cyanotic congenital heart disease. Although significant knowledge gaps exist, the sum of the data suggests that patients with congenital heart disease should be followed from an early age for the development of CKD. IMPLICATIONS: There is an opportunity to mitigate CKD progression and negative renal outcomes by instituting interventions such as stringent blood pressure control and reduction of proteinuria. There is a need to invest time, thought and money to fill existing knowledge gaps to improve health outcomes in this population. This review should serve as an impetus for generation of follow-up guidelines of kidney health evaluation in patients with congenital heart disease. PMID- 26266043 TI - Comparison of Measurement of Central Corneal Thickness with Spectral Domain Optical Coherence Tomography and Standard Ultrasonic Pachymeter in Premature Infants. AB - Purpose. To evaluate the repeatability of measurement of central corneal thickness (CCT) by spectral domain optical coherence (SD-OCT) in premature infants and compare it to CCT measurement by ultrasonic pachymetry (USP). Methods. Three CCT measurements of the left eyes of 50 premature infants were obtained by SD-OCT using the iVue system. 10 CCT measurements of each 28 left eyes of 28 infants were obtained by USP using the Pacscan 300P system. Bland Altman plots were developed and the limit of agreement (LoA) was determined to compare the mean of the SD-OCT and USP measurements. Results. No statistically significant difference was found among the 3 CCT measurements by SD-OCT. Both USP and SD-OCT have been performed for only left eyes of 28 of the 50 babies. Those results have been compared with each other. A statistically significant difference was found between the mean CCT measurements by SD-OCT and USP (p < 0.05). The LoA between the SD-OCT and USP measurements ranged from 11.4 to -64.1. Conclusions. CCT can be measured using the iVue SD-OCT system with a high level of repeatability. Although measurement of CCT by SD-OCT and USP is highly correlated, the 2 systems cannot be used interchangeably in premature infants. PMID- 26266044 TI - The Fundus Autofluorescence Spectrum of Punctate Inner Choroidopathy. AB - Purpose. To investigate the fundus autofluorescence (FAF) spectrum of punctate inner choroidopathy (PIC). Methods. This is a retrospective observational case series of 27 consecutive patients with PIC admitted from October 2013 to March 2015, who underwent short-wavelength- (SW-) and near-infrared- (NIR-) FAF imaging, spectral domain optical coherence tomography (SD-OCT), fluorescein angiography (FA), and indocyanine green angiography (ICGA). Results. There were three primary findings on the FAF imaging of patients with PIC. First, active PIC lesions revealed hypoautofluorescent spots with hyperautofluorescent margin. After the lesions regressed, the hyperautoflurescent margin faded. Second, subclinical and most of the atrophic PIC lesions appeared to be hypoautofluorescent spots. But subclinical PIC lesions were more distinctive on NIR-FAF imaging than on SW-FAF imaging. Third, hypoautofluorescent spots of PIC lesions coexisted with hyperautofluorescent patches on SW-FAF imaging. These hyperautofluorescent patches were demonstrated to be multiple evanescent white dot syndrome (MEWDS) or acute zonal occult outer retinopathy (AZOOR) lesions by subsequent multimodal imaging and faded during follow-up examinations. Conclusion. FAF imaging helps in noninvasively tracking the evolution of PIC lesions and identifying the combined MEWDS or AZOOR lesions, complementary to SD OCT and angiographic studies. PMID- 26266045 TI - Short-Term Intraocular Pressure Elevations after Combined Phacoemulsification and Implantation of Two Trabecular Micro-Bypass Stents: Prednisolone versus Loteprednol. AB - Objective. To compare the effects of prednisolone and of loteprednol after combined phacoemulsification and trabecular micro-bypass stent implantation (phaco-iStent). Methods. Patients who underwent phaco-iStent between April 2013 and November 2014 were identified by retrospective chart review. Postoperatively, they received either prednisolone (n = 38) or loteprednol (n = 58). Baseline data was compared. Primary outcomes including intraocular pressure (IOP) and number of glaucoma medications (NGM) were analyzed at preoperative visit, postoperative day 1, weeks 1-2, weeks 3-4, and months 2-3. Results. Both groups had similar preoperative parameters (p > 0.05). The mean IOP spike occurred at postoperative weeks 1-2 with an increase of 2.21 +/- 7.30 mmHg in the loteprednol group and 2.54 +/- 9.28 mmHg in the prednisolone group. It decreased by weeks 3-4 in both groups and continued to improve at months 2-3. NGM showed significant reduction (p < 0.0001) after the surgery and remained stable in both groups. No significant group effect or time-group interaction in IOP and NGM evolution was detected (p > 0.05). The proportions of patients needing paracentesis were similar between the two groups. Conclusion. Similar early IOP elevations after combined phaco-iStent occurred with both prednisolone and loteprednol. Facilitated glucocorticoid infusion, altered aqueous humor outflow, and local inflammation may be contributing factors. PMID- 26266046 TI - Pain Sensitisation in Women with Active Rheumatoid Arthritis: A Comparative Cross Sectional Study. AB - Objectives. In some rheumatoid arthritis (RA) patients, joint pain persists without signs of inflammation. This indicates that central pain sensitisation may play a role in the generation of chronic pain in a subgroup of RA. Our aim was to assess the degree of peripheral and central pain sensitisation in women with active RA compared to healthy controls (HC). Methods. 38 women with active RA (DAS28 > 2.6) and 38 female HC were included in, and completed, the study. Exclusion criteria were polyneuropathy, pregnancy, and no Danish language. Cuff Pressure Algometry measurements were carried out on the dominant lower leg. Pain threshold, pain tolerance, and pain sensitivity during tonic painful stimulation were recorded. Results. Women with active RA had significantly lower pain threshold (p < 0.01) and pain tolerance (p < 0.01) than HC. The mean temporal summation- (TS-) index in RA patients was 0.98 (SEM: 0.09) and 0.71 (SEM: 0.04) in HC (p < 0.01). Conclusion. Patients with active RA showed decreased pressure pain threshold compared to HC. In addition, temporal summation of pressure-pain was increased, indicating central pain sensitization, at least in some patients. Defining this subgroup of patients may be of importance when considering treatment strategies. PMID- 26266047 TI - Aloe vera Gel: Effective Therapeutic Agent against Multidrug-Resistant Pseudomonas aeruginosa Isolates Recovered from Burn Wound Infections. AB - Objective. Aloe vera is an herbal medicinal plant with biological activities, such as antimicrobial, anticancer, anti-inflammatory, and antidiabetic ones, and immunomodulatory properties. The purpose of this study was investigation of in vitro antimicrobial activity of A. vera gel against multidrug-resistant (MDR) Pseudomonas aeruginosa isolated from patients with burn wound infections. Methods. During a 6-month study, 140 clinical isolates of P. aeruginosa were collected from patients admitted to the burn wards of a hospital in Tehran, Iran. Antimicrobial susceptibility test was carried out against the pathogens using the A. vera gel and antibiotics (imipenem, gentamicin, and ciprofloxacin). Results. The antibiogram revealed that 47 (33.6%) of all isolates were MDR P. aeruginosa. The extract isolated from A. vera has antibacterial activity against all of isolates. Also, 42 (89.4%) isolates were inhibited by A. vera gel extract at minimum inhibitory concentration (MIC) <= 200 ug/mL. MIC value of A. vera gel for other isolates (10.6%) was 800 ug/mL. All of MDR P. aeruginosa strains were inhibited by A. vera at similar MIC50 and MIC90 200 ug/mL. Conclusion. Based on our results, A. vera gel at various concentrations can be used as an effective antibacterial agent in order to prevent wound infection caused by P. aeruginosa. PMID- 26266048 TI - Prognosis of Acute Kidney Injury and Hepatorenal Syndrome in Patients with Cirrhosis: A Prospective Cohort Study. AB - Background/Aims. Acute kidney injury is a common problem for patients with cirrhosis and is associated with poor survival. We aimed to examine the association between type of acute kidney injury and 90-day mortality. Methods. Prospective cohort study at a major US liver transplant center. A nephrologist's review of the urinary sediment was used in conjunction with the 2007 Ascites Club Criteria to stratify acute kidney injury into four groups: prerenal azotemia, hepatorenal syndrome, acute tubular necrosis, or other. Results. 120 participants with cirrhosis and acute kidney injury were analyzed. Ninety-day mortality was 14/40 (35%) with prerenal azotemia, 20/35 (57%) with hepatorenal syndrome, 21/36 (58%) with acute tubular necrosis, and 1/9 (11%) with other (p = 0.04 overall). Mortality was the same in hepatorenal syndrome compared to acute tubular necrosis (p = 0.99). Mortality was lower in prerenal azotemia compared to hepatorenal syndrome (p = 0.05) and acute tubular necrosis (p = 0.04). Ten participants (22%) were reclassified from hepatorenal syndrome to acute tubular necrosis because of granular casts on urinary sediment. Conclusions. Hepatorenal syndrome and acute tubular necrosis result in similar 90-day mortality. Review of urinary sediment may add important diagnostic information to this population. Multicenter studies are needed to validate these findings and better guide management. PMID- 26266049 TI - Fingolimod Treatment in Relapsing-Remitting Multiple Sclerosis Patients: A Prospective Observational Multicenter Postmarketing Study. AB - Objective. The aim of this prospective observational multicenter postmarketing study was to evaluate fingolimod efficacy in a real world clinical setting. Methods. One hundred forty-two subjects with relapsing-remitting multiple sclerosis (RRMS) were enrolled in three multiple sclerosis centers throughout Central and Southern Italy between January 2011 and September 2013. After enrollment, regular visits and EDSS assessment were scheduled every 3 months, and MRI scan was obtained every 12 months. Patients were followed up from 1 to 33 months (mean 14.95 +/- 9.15 months). The main efficacy endpoints included the proportion of patients free from clinical relapses, from disability progression, from magnetic resonance imaging activity, and from any disease activity. Results. Out of 142 patients enrolled in the study, 88.1% were free from clinical relapse and 69.0% were free from disability progression; 68.5% of patients remained free from new or newly enlarging T2 lesions and 81.7% of patients were free from gadolinium enhancing lesions. Overall the proportion of patients free from any disease activity was 41.9%. Conclusions. Our data in a real world cohort are consistent with previous findings that yield convincing evidence for the efficacy of fingolimod in patients with RRMS. PMID- 26266050 TI - Locoregional Recurrence Risk in Breast Cancer Patients with Estrogen Receptor Positive Tumors and Residual Nodal Disease following Neoadjuvant Chemotherapy and Mastectomy without Radiation Therapy. AB - Among breast cancer patients treated with neoadjuvant chemotherapy (NAC) and mastectomy, locoregional recurrence (LRR) rates are unclear in women with ER+ tumors treated with adjuvant endocrine therapy without postmastectomy radiation (PMRT). To determine if PMRT is needed in these patients, we compared LRR rates of patients with ER+ tumors (treated with adjuvant endocrine therapy) with women who have non-ER+ tumors. 85 consecutive breast cancer patients (87 breast tumors) treated with NAC and mastectomy without PMRT were reviewed. Patients were divided by residual nodal disease (ypN) status (ypN+ versus ypN0) and then stratified by receptor subtype. Among ypN+ patients (n = 35), five-year LRR risk in patients with ER+, Her2+, and triple negative tumors was 5%, 33%, and 37%, respectively (p = 0.02). Among ypN+/ER+ patients, lymphovascular invasion and grade three disease increased the five-year LRR risk to 13% and 11%, respectively. Among ypN0 patients (n = 52), five-year LRR risk in patients with ER+, Her2+, and triple negative tumors was 7%, 22%, and 6%, respectively (p = 0.71). In women with ER+ tumors and residual nodal disease, endocrine therapy may be sufficient adjuvant treatment, except in patients with lymphovascular invasion or grade three tumors where PMRT may still be indicated. PMID- 26266051 TI - Assessment of MRI Issues at 3 Tesla for a New Metallic Tissue Marker. AB - Purpose. To assess the MRI issues at 3 Tesla for a metallic tissue marker used to localize removal areas of tissue abnormalities. Materials and Methods. A newly designed, metallic tissue marker (Achieve Marker, CareFusion, Vernon Hills, IL) used to mark biopsy sites, particularly in breasts, was assessed for MRI issues which included standardized tests to determine magnetic field interactions (i.e., translational attraction and torque), MRI-related heating, and artifacts at 3 Tesla. Temperature changes were determined for the marker using a gelled-saline filled phantom. MRI was performed at a relatively high specific absorption rate (whole body averaged SAR, 2.9-W/kg). MRI artifacts were evaluated using T1 weighted, spin echo and gradient echo pulse sequences. Results. The marker displayed minimal magnetic field interactions (2-degree deflection angle and no torque). MRI-related heating was only 0.1 degrees C above background heating (i.e., the heating without the tissue marker present). Artifacts seen as localized signal loss were relatively small in relation to the size and shape of the marker. Conclusions. Based on the findings, the new metallic tissue marker is acceptable or "MR Conditional" (using current labeling terminology) for a patient undergoing an MRI procedure at 3 Tesla or less. PMID- 26266052 TI - Computer-Assisted Diagnosis of the Sleep Apnea-Hypopnea Syndrome: A Review. AB - Automatic diagnosis of the Sleep Apnea-Hypopnea Syndrome (SAHS) has become an important area of research due to the growing interest in the field of sleep medicine and the costs associated with its manual diagnosis. The increment and heterogeneity of the different techniques, however, make it somewhat difficult to adequately follow the recent developments. A literature review within the area of computer-assisted diagnosis of SAHS has been performed comprising the last 15 years of research in the field. Screening approaches, methods for the detection and classification of respiratory events, comprehensive diagnostic systems, and an outline of current commercial approaches are reviewed. An overview of the different methods is presented together with validation analysis and critical discussion of the current state of the art. PMID- 26266055 TI - Mesalazine-Induced Myopericarditis in a Patient with a Recent Diagnosis of Crohn's Disease: Apropos of a Case. AB - Mesalazine- (5-aminosalicylic acid-) containing products are a well-known treatment for inflammatory bowel disease, often as first line. Myocarditis is recognized as a very rare possible side effect of this drug treatment. We present a case of mesalazine-induced myopericarditis that was successfully improved by immediate cessation of the medication. PMID- 26266053 TI - Effect of Prolonged Moderate Exercise on the Changes of Nonneuronal Cells in Early Myocardial Infarction. AB - Myocardial infarction (MI) is one of the leading causes of death in developed countries and it is characterized by several associated symptomatologies and poor quality of life. Recent data showed a possible interaction between infarction and brain inflammation and activity. Previous studies have demonstrated the beneficial effect of exercise training on deterioration in cardiac function after MI. In this study we analyzed in sedentary and trained rats the microglia and astrocytes 48 hours after MI in PVN, thalamus, prefrontal cortex, and hippocampus through immunofluorescence approach. We found significant changes in specific microglia phenotypes in the brain areas analyzed together with astrocytes activation. Prolonged exercise normalized these morphological changes of microglia and astrocytes in the prefrontal cortex, hippocampus, and thalamus but not in the PVN. Our data suggest that there is an early brain reaction to myocardial infarction induction, involving nonneuronal cells, that is attenuated by the prolonged exercise. PMID- 26266056 TI - Biventricular Noncompaction Cardiomyopathy in an Adult with Unique Facial Dysmorphisms: Case Report and Brief Review. AB - Left ventricular noncompaction (LVNC) is a rare cardiomyopathy that is believed it to arise from an arrest in embryonic endomyocardial development. More recent studies suggest that it can be acquired later on in life sporadically. It may be accompanied by life-threatening complications, which are most commonly heart failure, arrhythmias, and thromboembolic events. We report a case of biventricular noncompaction cardiomyopathy in a 36-year-old man presenting for the first time with clinical heart failure as well as atrial arrhythmia. Transthoracic echocardiography (TTE) revealed LVNC with depressed ejection fraction (EF). Cardiac magnetic resonance imaging (MRI) further revealed a left atrial appendage thrombus as well as right ventricular noncompaction involvement. His physical exam was unique for a characteristic facial dysmorphisms pattern and developmental delays reminiscent of the earliest descriptions of LVNC in the pediatric population and it was rarely described in adult patients. This unique presentation underscores the importance of a better understanding of the genetics and natural course of LVNC. This will help us to elucidate the uncertainty surrounding its clinical management, discussed in a brief review of the literature following the case. PMID- 26266054 TI - Withaferin A Inhibits Nuclear Factor-kappaB-Dependent Pro-Inflammatory and Stress Response Pathways in the Astrocytes. AB - Several lines of evidence suggest that astrocytes play a key role in modulating the immune responses of the central nervous system (CNS) to infections, injuries, or pathologies. Yet, their contribution to these processes remains mostly elusive. Astroglia are endowed with a wide range of toll-like receptors (TLR) by which they can sense infectious agents as well as endogenous danger signals released by damaged cells. Here we demonstrate that the activation of astrocytic TLR4 by bacterial lipopolysaccharide (LPS) challenge can promote nuclear factor kappaB (NF-kappaB)-dependent induction of pro-inflammatory and stress response mediators, particularly Tumor Necrosis Factor alpha (TNFalpha), cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS). Since the steroid lactone Withaferin A was described to inhibit NF-kappaB activity in different cell types, we next determined the impact of this natural compound towards the identified astrocytic signalling pathway. Innate immune activation was induced by stimulation of the LPS/TLR4 axis in spinal cord astrocytes. We provide evidence that both pre-treating and post-treating the cells with Withaferin A attenuate astrocytic NF-kappaB activity as well as the consequent production of TNFalpha, COX-2, and iNOS induced by stimulation of the LPS/TLR4 pathway. This study suggests that Withaferin A may be an eligible candidate for the treatment of neuroinflammatory and stress conditions characterized by an important astrocytic input. PMID- 26266057 TI - Canine Gouging: A Taboo Resurfacing in Migrant Urban Population. AB - Cosmopolitan cities have become a pool of migrants from different parts of the world, who carry their cultural beliefs and superstitions with them around the globe. Canine gouging is a kind of infant oral mutilation (IOM) which is widely practiced among rural population of Africa where the primary tooth bud of the deciduous canine is enucleated. The belief is that the life threatening illnesses in children like vomiting, diarrhoea, and fevers are caused by worms which infest on tooth buds. This case report is of a 15-year-old Somalian born boy, who presented at the dental institute with intermittent pain in his lower right permanent canine which was associated with a discharging intra oral buccal sinus. The tooth was endodontically treated and then restored with composite. General dental practitioners need to be vigilant when encountered with tooth presenting unusual morphology, unilateral missing tooth, and shift in the midline due to early loss of deciduous/permanent canines. Identification of any such dental mutilation practice will need further counselling of the individual and family members. It is the duty of every dental professional to educate and safeguard the oral and dental health of general public. PMID- 26266058 TI - A Rare Presentation of Transfusional Hemochromatosis: Hypogonadotropic Hypogonadism. AB - Hemochromatosis is a disease caused by extraordinary iron deposition in parenchymal cells leading to cellular damage and organ dysfunction. beta thalassemia major is one of the causes of secondary hemochromatosis due to regular transfusional treatment for maintaining adequate levels of hemoglobin. Hypogonadism is one of the potential complications of hemochromatosis, usually seen in patients with a severe iron overload, and it shows an association with diabetes and cirrhosis in adult patients. We describe a patient with mild transfusional hemochromatosis due to beta-thalassemia major, presenting with central hypogonadism in the absence of cirrhosis or diabetes. Our case showed an atypical presentation with hypogonadotropic hypogonadism without severe hyperferritinemia, cirrhosis, or diabetes. With this case, we aim to raise awareness of hypogonadotropic hypogonadism in patients with intensive transfused thalassemia major even if not severe hemochromatosis so that hypogonadism related complications, such as osteoporosis, anergia, weakness, sexual dysfunction, and infertility, could be more effectively managed in these patients. PMID- 26266059 TI - A Novel Endoscopic Method to Relieve Food Impaction Using an Inflatable Balloon. AB - Food impaction in the esophagus is a relatively common medical emergency. Most of these food impactions are relieved spontaneously. But for complete esophageal food impactions or impactions not relieved spontaneously, traditional endoscopic methods like using a Roth net, polypectomy snare, or rat or alligator tooth forceps are used to gently manipulate the food material into the stomach. However, these methods may not work in certain circumstances. We present a case of proximal esophageal food impaction that was relieved using an inflatable balloon after the conventional methods proved unsuccessful. PMID- 26266060 TI - Cannabinoid Hyperemesis Syndrome: A Paradoxical Cannabis Effect. AB - Despite well-established antiemetic properties of marijuana, there has been increasing evidence of a paradoxical effect in the gastrointestinal tract and central nervous system, given rise to a new and underrecognized clinical entity called the Cannabinoid Hyperemesis Syndrome. Reported cases in the medical literature have established a series of patients exhibiting a classical triad of symptoms: cyclic vomiting, chronic marijuana use, and compulsive bathing. We present a case of a 29-year-old man whose clinical presentation strongly correlates with cannabinoid hyperemesis syndrome. Despite a diagnosis of exclusion, this syndrome should be considered plausible in the setting of a patient with recurrent intractable vomiting and a strong history of cannabis use as presented in this case. PMID- 26266061 TI - A Rare Cause of Acute Abdomen: Perforation of Double Meckel's Diverticulum. AB - Meckel's diverticulum is the most common congenital anomaly of the gastrointestinal tract. In this report, we aimed to represent a case of intestinal perforation, caused by double Meckel's diverticulum, which is a very rare entity in surgical practice. The patient was a 20-year-old Caucasian man, admitted to hospital with complaints of abdominal pain, nausea, and vomitting during the last 3 days. Physical examination indicated tenderness, rebound, and guarding in the right lower quadrant of abdomen. Abdominal X-ray revealed a few air-liquid levels in the left upper quadrant. In the operation, 2 Meckel's diverticula were observed, one at the antimesenteric side, at 70 cm distance to the ileocecal valve, approximately in 3 cm size, and the other between the mesenteric and antimesenteric sides, approximately in 5 cm size. The first one had been perforated at the tip and wrapped with omentum. A 30 cm ileal resection, including both diverticula with end-to-end anastomosis, was performed. The diagnosis of symptomatic Meckel's diverticulum is considerably hard, especially when it is complicated. Diverticulectomy or segmentary resections are therapeutic options. In patients with acute abdomen clinic, Meckel's diverticulum and its complications should be kept in mind, and the intestines should be observed for an extra diverticulum for caution although it is a very rare condition. PMID- 26266062 TI - Coccidioidomycosis Masquerading as Eosinophilic Ascites. AB - Endemic to the southwestern parts of the United States, coccidioidomycosis, also known as "Valley Fever," is a common fungal infection that primarily affects the lungs in both acute and chronic forms. Disseminated coccidioidomycosis is the most severe but very uncommon and usually occurs in immunocompromised individuals. It can affect the central nervous system, bones, joints, skin, and, very rarely, the abdomen. This is the first case report of a patient with coccidioidal dissemination to the peritoneum presenting as eosinophilic ascites (EA). A 27-year-old male presented with acute abdominal pain and distention from ascites. He had eosinophilia of 11.1% with negative testing for stool studies, HIV, and tuberculosis infection. Ascitic fluid exam was remarkable for low serum ascites albumin gradient (SAAG), PMN count >250/mm(3), and eosinophils of 62%. Abdominal imaging showed thickened small bowel and endoscopic testing negative for gastric and small bowel biopsies. He was treated empirically for spontaneous bacterial peritonitis, but no definitive diagnosis could be made until coccidioidal serology returned positive. We noted complete resolution of symptoms with oral fluconazole during outpatient follow-up. Disseminated coccidioidomycosis can present in an atypical fashion and may manifest as peritonitis with low SAAG EA. The finding of EA in an endemic area should raise the suspicion of coccidioidal dissemination. PMID- 26266063 TI - 12q14 Microdeletions: Additional Case Series with Confirmation of a Macrocephaly Region. AB - To date, there have been only a few reports of patients carrying a microdeletion in chromosome 12q14. These patients usually present with pre- and postnatal growth retardation, and developmental delay. Here we report on two additional patients with both genotype and phenotype differences. Similar to previously published cases, one patient has haploinsufficiency of the HMGA2 gene and shows severe short stature and developmental delay. The second patient is only one of a handful without the loss of the HMGA2 gene and shows a much better growth profile, but with absolute macrocephaly. This patient's deletion is unique and hence defines a likely macrocephaly locus that contributes to the general phenotype characterising the 12q14 syndrome. PMID- 26266064 TI - Pulmonary Limited MPO-ANCA Microscopic Polyangiitis and Idiopathic Lung Fibrosis in a Patient with a Diagnosis of IgA Nephropathy. AB - We present a case of a male patient with chronic renal insufficiency, due to crescentic glomerulonephritis with IgA deposits, who successively developed (idiopathic) thrombocytopenic purpura (ITP) and MPO-ANCA microscopic polyangiitis (MPA) with pulmonary fibrosis. The patient presented with cough, weight loss, and dyspnea on exertion. CT imaging and pulmonary function tests were compatible with interstitial pneumonitis with pulmonary fibrosis. Laboratory results showed high MPO-ANCA titers; the urinary sediment was bland. The patient was treated successfully with cyclophosphamide and methyl-prednisolone. This unique case illustrates the diagnostic and therapeutic challenges of an unusual presentation of microscopic polyangiitis presenting first as isolated kidney disease with recurrence in the form of pneumonitis without renal involvement, in association with renal IgA deposits and ITP as coexisting autoimmune conditions. PMID- 26266065 TI - Endoscopic Transnasal Approach for Cholesterol Granuloma of the Petrous Apex. AB - Cholesterol granulomas are rare round or ovoid cysts. They contain cholesterol crystals surrounded by foreign bodies of giant cells and are characterized by chronic inflammation. Large cholesterol granuloma can compress surrounding tissue especially cranial nerves. There are several types of surgery for the resection of cholesterol granuloma. We describe 4 cases of cholesterol granuloma operated on via transnasal endoscopic approach. In this report, we describe radiologic and pathologic features of this lesion and explain the advantages and disadvantages of transsphenoidal endoscopic approach for these rare lesions. PMID- 26266066 TI - A Case of Giant Uterine Lipoleiomyoma Simulating Malignancy. AB - Introduction. Uterine leiomyoma is the most common benign pathology in women and lipoleiomyoma is an extremely rare and specific type of leiomyoma. Here, we report an unusual case of giant pedunculated subserous lipoleiomyoma misdiagnosed preoperatively as leiomyosarcoma. Case. A 45-year-old woman admitted to our gynecology outpatient clinic for complaints of abdominal distention, tiredness, and pelvic pain for the last 6 months. Sonography and abdominal magnetic resonance imaging (MRI) showed a giant semisolid mass that filled whole abdominal cavity from pelvis to subdiaphragmatic area. A primary diagnosis of uterine sarcoma or ovarian malignancy was made. On operation, total abdominal hysterectomy with a pedunculated mass of size 30 * 23 * 12 cm and weighing 5.4 kg and bilateral salpingo-oophorectomy were performed. The histopathology revealed a lipoleiomyoma with extensive cystic and fatty degeneration without any malignancy. Discussion. The diagnosis of leiomyoma is done usually with pelvic ultrasound but sometimes it is difficult to reach a correct diagnosis especially in cases of giant and pedunculated lipoleiomyoma that included fatty tissue which may mimick malignancy. Conclusion. Subserous pedunculated giant lipoleiomyoma should be kept in mind in the differential diagnosis of leiomyosarcoma or ovarian malignancy. PMID- 26266067 TI - Alveolar Rhabdomyosarcoma in a 69-Year-Old Woman Receiving Glucagon-Like Peptide 2 Therapy. AB - A 69-year-old woman was diagnosed with alveolar rhabdomyosarcoma (ARMS) of the nasopharynx. She has a history of catastrophic thromboembolic event in the abdomen that caused short-gut syndrome and dependence on total parenteral nutrition (TPN) twelve hours per day. She was treated for short-gut syndrome with teduglutide, a glucagon-like peptide-2 (GLP-2) analog, which led to reduction of TPN requirements. However, a few months later, she developed metastatic alveolar rhabdomyosarcoma. Though a causative relationship is unlikely between the peptide and ARMS due to the brief time course between teduglutide therapy and sarcoma diagnosis, neoplastic growth may have been accelerated by the GLP-2 analog, causing release of IGF-1. The transmembrane receptor for IGF-1 is frequently overexpressed in ARMS and is implicated in cell proliferation and metastatic behavior. This case describes a rare incidence of metastatic alveolar rhabdomyosarcoma in a sexagenarian and possibly the first case reported associated with the use of teduglutide. Teduglutide was discontinued due to a potential theoretical risk of acceleration of sarcoma growth, and the patient's rhabdomyosarcoma is in remission following sarcoma chemotherapy. PMID- 26266068 TI - Carpal Tunnel Syndrome Caused by Tumoral Calcinosis. AB - We present a case of carpal tunnel syndrome caused by systemic tumoral calcinosis. A 54-year-old woman experienced hand numbness that persisted for nine months. She had no family history or medical problem. A plain radiograph of her right wrist showed a calcified mass on the volar side of the wrist joint. The patient also experienced pain in her contralateral wrist joint and both right and left shoulders, which had calcification on radiography around the joint. Her condition was diagnosed as carpal tunnel syndrome caused by systemic tumoral calcinosis and a resection biopsy was performed. Histopathological analysis of the biopsied specimen showed basophile deposition inside the fibrous connective tissue. At 14 months after the treatment, she no longer had pain or numbness in her fingers and there was no recurrence of the mass. This patient's condition is considered as a case of nonfamilial, systemic primary tumoral calcinosis. Since incomplete resection leads to a recurrence of the lesion, a follow-up radiography examination is needed to monitor symptom recurrence. PMID- 26266069 TI - Fracture of the Modular Neck in Total Hip Arthroplasty. AB - Modularity of the components in total hip arthroplasty has had an increase in popularity in the last decades. We present the case of a 53-year-old man with a history of avascular necrosis of the femoral head due to a hypophyseal adenoma. A total hip modular arthroplasty was implanted. Three and a half years after the surgery the patient attended the emergency room due to acute left hip pain with no prior traumatism. Radiological examination confirmed a fracture of the modular neck. A revision surgery was performed finding an important pseudotumoral well organized periprosthetic tissue reaction. Through an extended trochanteric osteotomy the femoral component was removed, and a straight-stem revision prosthesis implanted. There are several potential advantages when using modularity in total hip arthroplasty that surgeons may benefit from, but complications have arisen and must be addressed. Various circumstances such as large femoral head with a long varus neck, corrosion, patient's BMI, and activity level may participate in creating the necessary environment for fatigue failure of the implant. PMID- 26266070 TI - An Isolated Phlebolith on the Lip: An Unusual Case and Review of the Literature. AB - Background. Calcified thrombi are a common finding, especially in the pelvic veins. There are generally multiple thrombi, and they are generally associated with vascular malformations. Design. Herein we report a rare case of a single labial phlebolith, not associated with any other vascular lesion. We aim to alert clinicians to the possibility of the occurrence of vascular thrombi in the mouth and to describe the clinical and histological characteristics of such lesions in order to simplify the diagnosis and treatment. Furthermore, we have reviewed the English-language literature published since 1970 reporting oral (including masticatory muscles) phleboliths. Results. Twenty-nine cases of phleboliths have been reported in the literature since 1970. Only three of the reported phleboliths were solitary and not associated with other vascular lesions, as in the case presented here. Conclusion. Although phleboliths not associated with other vascular lesions are not common, clinicians should be aware of the existence of this pathology and include it as differential diagnosis of oral lesions. PMID- 26266071 TI - Oral Myiasis Caused by Cochliomyia hominivorax in a Disabled Person. AB - Myiasis is a parasitic disease caused by developing maggots of fly species, which can infect humans. Patients with special needs, especially those with severe neuropsychomotor limitations, may have oral manifestations of this disease. Here, we present a clinical case in which a disabled person was affected by oral myiasis caused by Cochliomyia hominivorax. Maggots were found in two ulcerated lesions, a 2 cm diameter lesion in the maxilla and a 6 cm diameter lesion in the mandible. Forty-five maggots were removed during inspection, whereas 75 maggots were surgically removed under general anesthesia with nasotracheal intubation. Dipyrone, ivermectin, and clindamycin were prescribed, and the patient remained hospitalized for 3 days. Seven days after surgical intervention, no maggots were observed. Our study emphasizes that dentists must recognize the symptoms and behaviors of parasitic diseases that affect the oral cavity. PMID- 26266072 TI - Clozapine-Induced Myocarditis: A Case Report of an Adolescent Boy with Intellectual Disability. AB - Background. Although known for its efficacy in treatment-resistant schizophrenia, the usage of clozapine has been limited due to concerns over potential adverse effects. Myocarditis, one potential fatal complication, can develop at any point during treatment but has been most commonly observed 2-3 weeks after clozapine initiation. Objective. A case of acute clozapine-induced myocarditis is described, highlighting the history, onset, and treatment course of presentation. There is a need to raise awareness of this potential complication, especially in the pediatric population. Results. 17-year-old Puerto Rican boy, with history of schizophrenia, disorganized type (treatment resistant), and intellectual disability, developed myocarditis on the thirteenth day following clozapine commencement. Initial presenting symptoms included tachycardia, lethargy, and vague gastrointestinal distress. Patient fully recovered after supportive medical care and clozapine discontinuation. Conclusions. Myocarditis is a known potential complication of clozapine initiation; however, due to its limited usage in the pediatric population, reported cases are limited. There is a need to establish evidence-based monitoring guidelines for clozapine usage, particularly in the pediatric population where the presentation may be atypical and clinical suspicion may be overlooked. PMID- 26266073 TI - Embolic Stroke as the Initial Manifestation of Systemic Lupus Erythematosus. AB - We present a case of a 21-year-old African-American female with no significant medical history, who presented to the emergency department with a one-week history of blurry and double vision. Ophthalmology evaluation revealed bilateral retinal artery occlusion. Further workup with imaging of the brain was consistent with an ischemic stroke. Hereditary hypercoagulable workup was unremarkable and initial testing for antiphospholipid syndrome was positive. She underwent transesophageal echocardiogram (TEE), which showed severe mitral regurgitation and thickening of mitral valve leaflets consistent with Libman-Sacks endocarditis. Autoimmune workup was positive for IF-ANA, anti-RNP, and anti-Smith antibody. She fulfilled 4/11 of the ACR criteria and met 5 of the SLICC (Systemic Lupus International Collaborating Clinics) criteria for lupus (nonscaring alopecia, thrombocytopenia, positive ANA, and positive anti-Smith and positive anti-phospholipid antibodies). This case highlights the importance of early recognition of underlying connective tissue diseases and timely management of these diseases in young patients with no previous manifestations of diseases. PMID- 26266074 TI - Single Incision Laparoscopic Cholecystectomy for Gallbladder Duplication. AB - Duplication of the gallbladder is a rare congenital anomaly of the gallbladder, with an estimated prevalence of 1-3 per 3800 individuals. Unless properly diagnosed preoperatively, it can lead to biliary tract injuries and postoperative complications which may require reoperative surgeries. While previously reported cases have been treated with conventional laparoscopic cholecystectomy (LC), treatment with single incision laparoscopic surgery (SILS) has not been reported yet. We herein present the case of a 58-year-old female with gallbladder duplication who was successfully treated with SILS cholecystectomy. PMID- 26266075 TI - Duodenal Obstruction as First Presentation of Metastatic Breast Cancer. AB - The metastatic breast cancer to the duodenum is rare in spite of common breast cancer. In this paper, we are reporting a rare case of 50-year-old lady who presented with intestinal obstruction as result of metastatic breast cancer which completely responds to chemotherapy. The tumor presents again as brain metastasis after stop of Herceptin due to cardiac toxicity. PMID- 26266076 TI - Insights into the respiratory tract microbiota of patients with cystic fibrosis during early Pseudomonas aeruginosa colonization. AB - Pseudomonas aeruginosa plays a major role in cystic fibrosis (CF) progression. Therefore, it is important to understand the initial steps of P. aeruginosa infection. The structure and dynamics of CF respiratory tract microbial communities during the early stages of P. aeruginosa colonization were characterized by pyrosequencing and cloning-sequencing. The respiratory microbiota showed high diversity, related to the young age of the CF cohort (mean age 10 years). Wide inter- and intra-individual variations were revealed. A common core microbiota of 5 phyla and 13 predominant genera was found, the majority of which were obligate anaerobes. A few genera were significantly more prevalent in patients never infected by P. aeruginosa. Persistence of an anaerobic core microbiota regardless of P. aeruginosa status suggests a major role of certain anaerobes in the pathophysiology of lung infections in CF. Some genera may be potential biomarkers of pulmonary infection state. PMID- 26266077 TI - An in vivo morphometry study on the standard transsylvian trajectory for mesial temporal lobe epilepsy surgery. AB - A safe and appropriate surgical approach to the medial temporal structure is a prerequisite to perform surgeries for temporal lobe epilepsy. We used in vivo morphometry to identify the standard direction for entry into the inferior horn of the lateral ventricle via the Sylvian fissure: an important initial step in performing transsylvian selective amygdalohippocampectomy. 3D magnetic resonance images obtained from 28 patients without intra-parenchymal lesions were re oriented to demonstrate all points in the Talairach space of the brain. The limen insulae and the midpoint between the hippocampal sulcus and the innominate sulcus on the coronal slice through the posterior edge of the amygdala were defined as the start and target points, respectively. We evaluated the direction of the vector between these two points and its validity in the brain of 12 patients with temporal lobe epilepsy. The direction of the mean approach vector was 52.4 degrees posteriorly and 16.2 degrees inferiorly. The mean approach vector on the axial plane showed the approximate parallelism with the sphenoid ridge in individual cases. The computer simulation revealed that our average approach vector correctly entered the inferior horn of the lateral ventricle in all temporal lobe epilepsy brains. In vivo morphometry may contribute to the further development of safe and minimally-invasive neurosurgical procedures. PMID- 26266078 TI - Chronic hyperglycemia increases the risk of lateral epicondylitis: the Locomotive Syndrome and Health Outcome in Aizu Cohort Study (LOHAS). AB - BACKGROUND: Although humeral epicondylitis is a common health problem, there have been no reports that describe its prevalence in Japanese general population, and relatively little is known about its etiology and associated risk factors. QUESTIONS/PURPOSES: This study aimed to clarify the prevalence of humeral epicondilitis in Japanese general population, and investigate the associated risk factors using the data from a cross-sectional study of the Locomotive Syndrome and Health Outcome in Aizu Cohort Study (LOHAS). METHODS: A total of 1,777 participants who participated in health checkups conducted at rural area in Japan in 2010 were enrolled. The prevalence of lateral and medial epicondylitis was investigated. Logistic regression models were performed to examine the relationship between lateral epicondylitis and correlated factors such as occupational status, smoking and alcohol preferences, and medical characteristics. RESULTS: The overall prevalence of lateral and medial epicondylitis was 2.5 % and 0.3 %, respectively. A shortened version of the disabilities of the arm, shoulder and hand (The QuickDASH) score was significantly higher in subjects with lateral epicondylitis than in those without (15.0 +/- 12.7 vs 8.5 +/- 11.1). Subjects with definite chronic hyperglycemia (HbA1c >= 6.5) showed a 3.37-times higher risk of lateral epicondylitis than those with favorable glycemic control (HbA1c < 5.5) (95 % confidence interval (CI) 1.16-8.56). Age and sex, as well as occupational status, smoking and alcohol preference, and other metabolic factors were not significantly related to higher risk of lateral epicondylitis. CONCLUSIONS: Lateral epicondylitis influences activities of daily living. Chronic hyperglycemia might be one of the risk factor for lateral epicondylitis. CLINICAL RELEVANCE: Chronic hyperglycemia is significantly associated with lateral epicondylitis. PMID- 26266079 TI - Virulence of Candida albicans isolated from HIV infected and non infected individuals. AB - Candida sp contributes 33.1 % of fungal infections among HIV patients. Among the species of the genus Candida, Candida albicans is the most frequently isolated from HIV patients. This study aimed to analyze putative virulence factors of C. albicans isolated from oral cavities of HIV infected patients and healthy individuals. Twenty isolates from HIV infected patients and fourteen from healthy individuals were analyzed for phenotypic switching, cell growth rate, hyphae formation, hemolytic activity and biofilm formation characteristics. The frequency of phenotypic switching was low in both groups. The cell growth rate of C. albicans from HIV infected patients were significantly higher than those from healthy individuals (p < 0.001). After 48 h incubation, the concentration of C. albicans isolated from HIV infected patients was 8.6 * 10(6) cells/ml while the concentration of C. albicans isolated from healthy individuals was 7.8 * 10(6) cells/ml. After 72 h incubation, the concentration of C. albicans isolated from HIV infected patients was 9.5 * 10(6) cells/ml while the concentration of C. albicans isolated from healthy individuals was 8.2 * 10(6) cells/ml. In contrast, the hemolytic activity of C. albicans isolated from healthy individuals were significantly higher compared to those from HIV infected patients (p < 0.001) at both aerobic (6 vs. 3.5 mm) and anaerobic (3.8 vs. 1.3 mm) conditions. The percentages of hyphae forming cells were higher in C. albicans collected from HIV infected patients (27.5 %) compared to the healthy individual group (14.7 %). However, this trend was not statistically significant (p = 0.1). Candida albicans isolated from HIV infected patients have similar ability to develop biofilms compared to those from healthy individuals. (OR = 4.2; 95 % CI 0.724-26.559). The virulence factors of C. albicans isolated from HIV infected patients were not significantly different from those of healthy individuals. The results add new insights into the contribution of virulence factors in the pathogenesis of C. albicans infection in HIV infected patients. PMID- 26266080 TI - Migraine treatment: a chain of adverse effects. AB - This clinical vignette presents a 14 years old female, with a past medical history relevant only for migraine with typical aura of less than monthly frequency, complaining of a severe unilateral headache with rising intensity for the previous 4 h, associated with nausea, vomiting, photophobia and phonophobia. This episode of migraine with aura in a patient with recurrent migraine was complicated by side effects of medical diagnostic and therapeutic procedures (extrapyramidal symptoms, delirium, post-lumbar puncture headache, hospital admission) all of which could have been prevented-quaternary prevention. This case illustrates several important messages in migraine management: (1) use of acetaminophen is not based in high-quality evidence and better options exist; (2) among youngsters, domperidone should be preferred over metoclopramide because it does not cross the blood-brain barrier; (3) moderate to severe migraine crisis can be managed with triptans in teenagers over 12 years old; (4) it is important to recognize adverse drug effects; (5) harmful consequences of medical interventions do occur; (6) the school community must be informed about chronic diseases of the young. PMID- 26266081 TI - Dancing cheek to cheek: Cryptococcus neoformans and phagocytes. AB - Meningoencephalitis caused by Cryptococcus neoformans (Cn) has become one of the leading causes of mortality in AIDS patients. Understanding the interactions between Cn and phagocytes is fundamental in exploring the pathogenicity of cryptococcal meningoencephalitis. Cn may be extracellular or contained in the monocytes, macrophages, neutrophils, dendritic cells and even endothelial cells. The internalized Cn may proliferate inside the host cells, or cause the lysis of host cells, or leave the host cells via non-lytic exocytosis, or even hijack the host cells (Trojan horse) for the brain dissemination, which are regulated by microbe factors and also immune molecules. Coexistence of protective and deleterious roles of phagocytes in the progression of cryptococcosis warrant further investigation. PMID- 26266082 TI - Evaluating the reliability of the Attitudes to Randomized Trial Questionnaire (ARTQ) in a predominantly African American sample. AB - PURPOSE: To evaluate the reliability of the Attitudes to Randomized Trial Questionnaire (ARTQ) in measuring perceptions of cancer clinical trials in a predominantly African American (AA) sample in South Carolina (SC). METHODS: Principal Component Analysis (PCA) and Cronbach's alpha estimates were used to assess the reliability of the ARTQ in a convenience sample of 315 participants (81.4 % AA) who were recruited from 2008 to 2013, and who live in eleven different counties in South Carolina with high rates of racial disparities in cancer mortality rates. RESULTS: Slightly more than half of the 315 participants had at least a college education (77.9 %), 84.8 % were female, and 53.1 % had an annual income of $40,000 or more. In this study, PCA confirmed that the ARTQ is unidimensional. Cronbach's alpha for the ARTQ was 0.86. CONCLUSION: The ARTQ displayed strong evidence of high statistical reliability. This analysis has great implications for future research because it represents the first test of reliability of the ARTQ in a predominantly African American sample and lays the groundwork for use of the ARTQ in future studies in diverse populations. PMID- 26266083 TI - Simulation-based training for determination of brain death by pediatric healthcare providers. AB - BACKGROUND: Low competency for determination of brain death (BD) and unfamiliarity with Japanese BD (JBD) criteria among pediatricians were highlighted in previous nationwide studies. Because the JBD criteria were amended in 2010 to allow organ donation from pediatric brain-dead donors, we created a 2 day training course to assess knowledge and improve skill in the determination and diagnosis of pediatric BD. METHODS: The course consisted of two modules: a multistation round session and a group discussion session, and was bookended by a before and after 20-question test. In the multistation round session, participants rotated between stations staffed by expert faculty members. For hands-on skill development, we used the Sim Junior 3GTM simulation mannequin (Laerdal Medical, Wappingers Falls, NY, USA) for structured simulations. In the group discussion session, we implemented simulation-based role playing to practice decision making in prepared scenarios of complicated clinical situations. We investigated the participants' impressions of the course by self scoring and questionnaires. RESULTS: Of 147 pediatric healthcare providers from multiple specialties who participated in this course, 145 completed the entire process. The course was evaluated in three aspects with self-scoring and questionnaires: (1) value (4.58 +/- 0.64; range 1-5); (2) time schedule (2.40 +/- 0.61; range 1-3); and (3) difficulty (2.89 +/- 0.43; range 1-5). Finally, participants scored the entire course program (9.64 +/- 1.69; range 1-11). Various positive feedbacks were obtained from a total of 93 participants. Post test scores (83.6 %) were significantly higher than pre-test scores (62.9 %). CONCLUSION: This simulation-based course represents an effective method to train pediatric healthcare providers in determining BD in Japan and may improve baseline knowledge of BD among participants. PMID- 26266084 TI - The effects of distal interlocking screws on torsional stability in three-part intertrochanteric hip fractures. AB - OBJECTIVE: Many surgeons currently use long cephomedullary nails for the treatment of intertrochanteric fractures. The optimal indications for deploying distal interlocks are still debatable. This study examined the torsional biomechanical properties of 3-part intertrochanteric femur fractures in a cadaveric bone model using two different distal fixation strategies, an unlocked long cephalomedullary nail versus a dynamically locked nail. Our hypothesis is that a long cephalomedullary nail does not require distal locking fixation when used for treatment of a 3-part intertrochanteric fracture. METHODS: Five matched pairs of cadaveric femora were randomly assigned to one of two distal fixation treatment groups; a single distal interlock screw placed in the dynamic orientation or no distal fixation. A 3-part intertrochanteric fracture was produced. Specimens were potted and mounted in a double gimbal fixture facilitating unconstrained motion in the sagittal and coronal planes. Specimens were cyclically loaded dynamically in both internal and external rotation. Range of motion, internal and external rotation stiffness, torsion stiffness, torsion yield and ultimate torsion magnitude were calculated. RESULTS: The samples instrumented with a distal locking screw reported statistically greater external rotational stiffness than the unlocked samples in nondestructive testing. The results of the destructive data demonstrated no statistical difference between the locked and unlocked group with regard to yield torque (p = 0.282), peak torque (p = 0.340), stiffness (p = 0.220), displacement at yield torque (p = 0.0605), and displacement at peak torque (p = 0.280). CONCLUSION: Distal locking of a long cephalomedullary nail increases the stiffness of the nail-femur construct in a 3-part biomechanical fracture model. However, our testing illustrates that an unlocked construct will tolerate at least equal stress before catastrophic failure in a torsional loading model. PMID- 26266085 TI - Cardiorenal syndrome type 5: in vitro cytotoxicity effects on renal tubular cells and inflammatory profile. AB - Background. Cardiorenal Syndrome Type 5 (CRS Type 5) reflects concomitant cardiac and renal dysfunctions in the setting of a wide spectrum of systemic disorders. Our aim was to study in vitro effects of CRS Type 5 plasma on renal tubular cells (RTCs), in terms of cellular death and the characterization of inflammatory plasma profile in these patients. Material and Methods. We enrolled 11 CRS Type 5 patients from ICU and 16 healthy controls. Plasma from patients and controls was incubated with renal tubular cells (RTCs) and cell death was evaluated. Plasma cytokines were detected. Results. RTCs incubated with CRS Type 5 plasma showed significantly higher apoptosis and necrosis with respect to controls. Plasma cytokine profile of CRS Type 5 patients was significantly different from controls: we observed the production of pro- and anti-inflammatory mediators in these patients. Caspase-3, caspase-8, and caspase-9 were activated in cells treated with CRS Type 5 plasma compared to controls. Conclusions. Our results underline the cytotoxic effect of CRS Type 5 mediators on RTC viability, probably due to the activation of both intrinsic and extrinsic pathways of apoptosis and to the deregulation of cytokine release. The consequence may be the damage of distant organs which lead to the worsening of condition of patients. PMID- 26266086 TI - High percentage of ADAM-10 positive melanoma cells correlates with paucity of tumor-infiltrating lymphocytes but does not predict prognosis in cutaneous melanoma patients. AB - ADAM-10 (CDw156, CD156c, and kuzbanian) is a protein belonging to a superfamily of metalloproteases, enzymes capable of degrading the extracellular matrix. ADAMs have also been shown to be primarily involved in ectodomain cleavage. The aim of the study was to assess the expression and intracellular location of ADAM-10 in 104 primary skin melanomas and 16 metastatic lesions from regional lymph nodes. Also, prognostic significance of ADAM-10 expression in primary tumor cells and metastatic lesion cells was evaluated during 5-year observation. It was revealed that high expression of ADAM-10 positive cells was strictly related with lower intensity of tumor-infiltrating lymphocytes (P = 0.037), which suggests that ADAM 10 regulates immunoresponse in melanoma initiation and progression. No statistically significant correlations were found between ADAM-10 expression in primary tumor cells and nodal metastases and other histopathological parameters analyzed. Decreased immunoreactivity of ADAM-10 in cancer cells from regional lymph nodes was correlated with worse prognosis; however this correlation was statistically nonsignificant (P = 0.065). Review of the literature shows that our study is the first one ever to describe the significance of ADAM-10 expression in correlation with detailed histopathological parameters of the primary tumor and data on long-term survival of cutaneous melanoma patients. PMID- 26266087 TI - Glucagon-to-insulin ratio is pivotal for splanchnic regulation of FGF-21 in humans. AB - BACKGROUND & AIMS: Fibroblast growth factor 21 (FGF-21) is a liver-derived metabolic regulator induced by energy deprivation. However, its regulation in humans is incompletely understood. We addressed the origin and regulation of FGF 21 secretion in humans. METHODS: By determination of arterial-to-venous differences over the liver and the leg during exercise, we evaluated the organ specific secretion of FGF-21 in humans. By four different infusion models manipulating circulating glucagon and insulin, we addressed the interaction of these hormones on FGF-21 secretion in humans. RESULTS: We demonstrate that the splanchnic circulation secretes FGF-21 at rest and that it is rapidly enhanced during exercise. In contrast, the leg does not contribute to the systemic levels of FGF-21. To unravel the mechanisms underlying the regulation of exercise induced hepatic release of FGF-21, we manipulated circulating glucagon and insulin. These studies demonstrated that in humans glucagon stimulates splanchnic FGF-21 secretion whereas insulin has an inhibitory effect. CONCLUSIONS: Collectively, our data reveal that 1) in humans, the splanchnic bed contributes to the systemic FGF-21 levels during rest and exercise; 2) under normo physiological conditions FGF-21 is not released from the leg; 3) a dynamic interaction of glucagon-to-insulin ratio regulates FGF-21 secretion in humans. PMID- 26266088 TI - Glucose intolerance induced by blockade of central FGF receptors is linked to an acute stress response. AB - OBJECTIVE: Central administration of ligands for fibroblast growth factor receptors (FGFRs) such as fibroblast growth factor-19 (FGF19) and FGF21 exert glucose-lowering effects in rodent models of obesity and type 2 diabetes (T2D). Conversely, intracerebroventricular (icv) administration of the non-selective FGFR inhibitor (FGFRi) PD173074 causes glucose intolerance, implying a physiological role for neuronal FGFR signaling in glucose homeostasis. The current studies were undertaken to identify neuroendocrine mechanisms underlying the glucose intolerance induced by pharmacological blockade of central FGFRs. METHODS: Overnight fasted, lean, male, Long-Evans rats received icv injections of either PD173074 or vehicle (Veh) followed 30 min later by performance of a frequently sampled intravenous glucose tolerance test (FSIGT). Minimal model analysis of glucose and insulin data from the FSIGT was performed to estimate insulin-dependent and insulin-independent components of glucose disposal. Plasma levels of lactate, glucagon, corticosterone, non-esterified free fatty acids (NEFA) and catecholamines were measured before and after intravenous (iv) glucose injection. RESULTS: Within 20 min of icv PD173074 injection (prior to the FSIGT), plasma levels of lactate, norepinephrine and epinephrine increased markedly, and each returned to baseline rapidly (within 8 min) following the iv glucose bolus. In contrast, plasma glucagon levels were not altered by icv FGFRi at either time point. Consistent with a previous report, glucose tolerance was impaired following icv PD173074 compared to Veh injection and, based on minimal model analysis of FSIGT data, this effect was attributable to reductions of both insulin secretion and the basal insulin effect (BIE), consistent with the inhibitory effect of catecholamines on pancreatic beta-cell secretion. By comparison, there were no changes in glucose effectiveness at zero insulin (GEZI) or the insulin sensitivity index (SI). To determine if iv glucose (given during the FSIGT) contributed to the rapid resolution of the sympathoadrenal response induced by icv FGFRi, we performed an additional study comparing groups that received iv saline or iv glucose 30 min after icv FGFRi. Our finding that elevated plasma catecholamine levels returned rapidly to baseline irrespective of whether rats subsequently received an iv bolus of saline or glucose indicates that the rapid reversal of sympathoadrenal activation following icv FGFRi was unrelated to the subsequent glucose bolus. CONCLUSIONS: The effect of acute inhibition of central FGFR signaling to impair glucose tolerance likely involves a stress response associated with pronounced, but transient, sympathoadrenal activation and an associated reduction of insulin secretion. Whether this effect is a true consequence of FGFR blockade or involves an off-target effect of the FGFR inhibitor requires additional study. PMID- 26266089 TI - Knockout of STAT3 in skeletal muscle does not prevent high-fat diet-induced insulin resistance. AB - OBJECTIVE: Increased signal transducer and activator of transcription 3 (STAT3) signaling has been implicated in the development of skeletal muscle insulin resistance, though its contribution, in vivo, remains to be fully defined. Therefore, the aim of this study was to determine whether knockout of skeletal muscle STAT3 would prevent high-fat diet (HFD)-induced insulin resistance. METHODS: We used Cre-LoxP methodology to generate mice with muscle-specific knockout (KO) of STAT3 (mKO). Beginning at 10 weeks of age, mKO mice and their wildtype/floxed (WT) littermates either continued consuming a low fat, control diet (CON; 10% of calories from fat) or were switched to a HFD (60% of calories from fat) for 20 days. We measured body composition, energy expenditure, oral glucose tolerance and in vivo insulin action using hyperinsulinemic-euglycemic clamps. We also measured insulin sensitivity in isolated soleus and extensor digitorum longus muscles using the 2-deoxy-glucose (2DOG) uptake technique. RESULTS: STAT3 protein expression was reduced ~75-100% in muscle from mKO vs. WT mice. Fat mass and body fat percentage did not differ between WT and mKO mice on CON and were increased equally by HFD. There were also no genotype differences in energy expenditure or whole-body fat oxidation. As determined, in vivo (hyperinsulinemic-euglycemic clamps) and ex vivo (2DOG uptake), skeletal muscle insulin sensitivity did not differ between CON-fed mice, and was impaired similarly by HFD. CONCLUSIONS: These results demonstrate that STAT3 activation does not underlie the development of HFD-induced skeletal muscle insulin resistance. PMID- 26266090 TI - A novel crosstalk between Alk7 and cGMP signaling differentially regulates brown adipocyte function. AB - OBJECTIVE: Obesity is an enormous burden for patients and health systems world wide. Brown adipose tissue dissipates energy in response to cold and has been shown to be metabolically active in human adults. The type I transforming growth factor beta (TGFbeta) receptor Activin receptor-like kinase 7 (Alk7) is highly expressed in adipose tissues and is down-regulated in obese patients. Here, we studied the function of Alk7 in brown adipocytes. METHODS: Using pharmacological and genetic tools, Alk7 signaling pathway and its effects were studied in murine brown adipocytes. Brown adipocyte differentiation and activation was analyzed. RESULTS: Alk7 is highly upregulated during differentiation of brown adipocytes. Interestingly, Alk7 expression is increased by cGMP/protein kinase G (PKG) signaling, which enhances brown adipocyte differentiation. Activin AB effectively activates Alk7 and SMAD3 signaling. Activation of Alk7 in brown preadipocytes suppresses the master adipogenic transcription factor PPARgamma and differentiation. Stimulation of Alk7 during late differentiation of brown adipocytes reduces lipid content and adipogenic marker expression but enhances UCP1 expression. CONCLUSIONS: We found a so far unknown crosstalk between cGMP and Alk7 signaling pathways. Tight regulation of Alk7 is required for efficient differentiation of brown adipocytes. Alk7 has differential effects on adipogenic differentiation and the development of the thermogenic program in brown adipocytes. PMID- 26266092 TI - Corrigendum to "Nuclear Factor-Y is an adipogenic factor that regulates leptin gene expression"[Mol Metab 4 (2015) 392-405]. AB - [This corrects the article DOI: 10.1016/j.molmet.2015.02.002.]. PMID- 26266091 TI - Macrophages are essential for CTGF-mediated adult beta-cell proliferation after injury. AB - OBJECTIVE: Promotion of endogenous beta-cell mass expansion could facilitate regeneration in patients with diabetes. We discovered that the secreted protein CTGF (aka CCN2) promotes adult beta-cell replication and mass regeneration after injury via increasing beta-cell immaturity and shortening the replicative refractory period. However, the mechanism of CTGF-mediated beta-cell proliferation is unknown. Here we focused on whether CTGF alters cells of the immune system to enhance beta-cell replication. METHODS: Using mouse models for 50% beta-cell ablation and conditional, beta-cell-specific CTGF induction, we assessed changes in immune cell populations by performing immunolabeling and gene expression analyses. We tested the requirement for macrophages in CTGF-mediated beta-cell proliferation via clodronate-based macrophage depletion. RESULTS: CTGF induction after 50% beta-cell ablation increased both macrophages and T-cells in islets. An upregulation in the expression of several macrophage and T-cell chemoattractant genes was also observed in islets. Gene expression analyses suggest an increase in M1 and a decrease in M2 macrophage markers. Depletion of macrophages (without changes in T cell number) blocked CTGF-mediated beta-cell proliferation and prevented the increase in beta-cell immaturity. CONCLUSIONS: Our data show that macrophages are critical for CTGF-mediated adult beta-cell proliferation in the setting of partial beta-cell ablation. This is the first study to link a specific beta-cell proliferative factor with immune-mediated beta cell proliferation in a beta-cell injury model. PMID- 26266093 TI - Acute acalculous cholecystitis complicating chemotherapy for acute myeloblastic leukemia. AB - Acute acalculous cholecystitis is a rare complication in the treatment of acute myeloblastic leukemia. Diagnosis of acute acalculous cholecystitis remains difficult during neutropenic period. We present two acute myeloblastic leukemia patients that developed acute acalculous cholecystitis during chemotherapy induced neutropenia. They suffered from fever, vomiting and acute pain in the epigastrium. Ultrasound demonstrated an acalculous gallbladder. Surgical management was required in one patient and conservative treatment was attempted in the other patient. None treatment measures were effective and two patients died. Acute acalculous cholecystitis is a serious complication in neutropenic patients. Earlier diagnosis could have expedited the management of these patients. PMID- 26266094 TI - Pseudo-Guillain-Barre syndrome masking acute myeloid leukemia relapse: Brief report and review. AB - Central nervous system (CNS) relapse is not a rare presentation in acute myeloid leukemia (AML) as its incidence ranges between 2% and 9%. It manifests with meningeal leukemia, cranial nerve palsies or cerebral mesenchymal myeloid sarcoma. We herein report the case of a 69 year-old female that presented a pseudo-Guillain-Barre syndrome masking an AML CNS relapse. Her symptoms completely resolved upon administration of a tailored treatment. This case suggests that puzzling neurological manifestations in patients with a history of AML should be considered as a CNS recurrence and investigated accordingly even in the context of normal imaging findings. PMID- 26266095 TI - Chronic-phase chronic myeloid leukemia: Not always a reassuring diagnosis. AB - Primary resistance to tyrosine-kinase inhibitors (TKIs) is quite uncommon in chronic-phase Chronic Myeloid Leukemia (CML) and related to still poorly understood mechanisms, as ABL mutations are rarely detected in primary resistant patients. We report the challenging case of a CML patient who was resistant to multiple TKIs because of different emerging ABL mutations and became pregnant while on Nilotinib therapy despite repeated and clear discouragement to conceive. She decided to continue with her pregnancy, showing an admirable and incredible perseverance in the pursuit of her personal aims. PMID- 26266097 TI - Genetic basis of cystinosis in Tunisian patients: Identification of novel mutation in CTNS gene. AB - Nephropathic cystinosis (NC) is an autosomal recessive disorder characterized by defective transport of cystine across the lysosomal membrane and resulting in renal, ophthalmic, and other organ abnormalities. Mutations in the CTNS gene cause a deficiency of the transport protein, cystinosin. This study was performed to investigate mutations of the CTNS gene in three Tunisian families with NC. Polymerase chain reaction (PCR), ARMS multiplex PCR and direct sequencing were performed for molecular characterization of the CTNS gene in 3 unrelated Tunisian patients and their parents. Based on family history, prenatal diagnosis (PND) was performed in fetal DNA isolated from chorionic villi obtained at 10-12 weeks of gestation. None of the patients showed the most common 57-kb deletion in heterozygous or homozygous status. One patient was homozygous for the previously reported mutation c.1515G > A (p.G308R). One patient presented the novel gross deletion of 20,327 bp. One was homozygote for the previously reported mutation c.771_793del (p.Gly258Serfs*30). In addition, eight polymorphisms were identified in the 3 patients and their parents. The prenatal diagnosis in one family showed that the fetus DNA was heterozygous for the c.771_793del (p.Gly258Serfs*30) mutation. This study expands the mutational and population spectrum of NC, representing the first molecular diagnosis of NC in Tunisian population. The mutation screening of the CTNS gene was used for prenatal diagnosis to prevent and/or limit this inheritable disease in our country where the families are particularly large and have a high rate of consanguinity. PMID- 26266098 TI - Oligometastatic disease, the curative challenge in radiation oncology. AB - The concept of oligometastatic disease was first described by Hellman and Weichselbaum in 1995. The mere insight of this concept led to the hypothesis that this disease may be cured using local ablative weapons. Surgery has already demonstrated this hypothesis. Surgery limitations, either technical or due to refusal or associated comorbidity, have led to implement alternative ablative options such as stereotactic body radiation therapy (SBRT). SBRT evolved from (stereotactic radiosurgery) because of the need to irradiate extracranial lesions and has been shown to be safe and effective. SBRT achieves local control rates ranging from 70%-90%, but highly variable survival rates depending on the group analyzed. Series with heterogeneous metastatic sites and tumor origin have reported 20% survival rates at 2-3 years, similar to those achieved with surgery. Despite its excellent results, SBRT still faces significant clinical challenges. Its optimal integration with systemic treatment is unknown, and response assessment is very difficult. However, the greatest challenge lies in selection of patients most likely to remain oligometastatic, those who will most benefit from the technique. Biomarkers, molecular signatures, that accurately predict the biological behavior of malignancy are needed. The expression profile of specific miRNAs has been shown to have a potential in this regard. PMID- 26266096 TI - Individual classification of ADHD children by right prefrontal hemodynamic responses during a go/no-go task as assessed by fNIRS. AB - While a growing body of neurocognitive research has explored the neural substrates associated with attention deficit hyperactive disorder (ADHD), an objective biomarker for diagnosis has not been established. The advent of functional near-infrared spectroscopy (fNIRS), which is a noninvasive and unrestrictive method of functional neuroimaging, raised the possibility of introducing functional neuroimaging diagnosis in young ADHD children. Previously, our fNIRS-based measurements successfully visualized the hypoactivation pattern in the right prefrontal cortex during a go/no-go task in ADHD children compared with typically developing control children at a group level. The current study aimed to explore a method of individual differentiation between ADHD and typically developing control children using multichannel fNIRS, emphasizing how spatial distribution and amplitude of hemodynamic response are associated with inhibition-related right prefrontal dysfunction. Thirty ADHD and thirty typically developing control children underwent a go/no-go task, and their cortical hemodynamics were assessed using fNIRS. We explored specific regions of interest (ROIs) and cut-off amplitudes for cortical activation to distinguish ADHD children from control children. The ROI located on the border of inferior and middle frontal gyri yielded the most accurate discrimination. Furthermore, we adapted well-formed formulae for the constituent channels of the optimized ROI, leading to improved classification accuracy with an area under the curve value of 85% and with 90% sensitivity. Thus, the right prefrontal hypoactivation assessed by fNIRS would serve as a potentially effective biomarker for classifying ADHD children at the individual level. PMID- 26266099 TI - Concurrent chemoradiation for high-risk prostate cancer. AB - There are estimated to be 220800 cases of prostate cancer diagnosed in 2015, making up 26% of all cancer diagnoses. Fortunately, adenocarcinoma of the prostate is often a highly treatable malignancy. Even though the majority of prostate cancer patients present with localized disease, prostate cancer still accounts for over 27000 deaths a year. There is a subset of patients that are likely to recur after locoregional treatment that is thought of as a "high-risk" population. This more aggressive subset includes patients with clinical stage greater than T2b, Gleason score greater than 7, and prostate specific antigen greater than 20 ng/dL. The rate of biochemical relapse in this high risk group is 32%-70% within five years of definitive focal therapy. Given these discouraging outcomes, attempts have been made to improve cure rates by radiation dose escalation, addition of androgen depravation therapy, and addition of chemotherapy either sequentially or concurrently with radiation. One method that has been shown to improve clinical outcomes is the addition of chemotherapy to radiotherapy for definitive treatment. Concurrent chemoradiation with 5 fluorouracil, estramustine phosphate, vincristine, docetaxel, and paclitaxel has been studied in the phase I and/or II setting. These trials have identified the maximum tolerated dose of chemotherapy and radiation that can be safely delivered concurrently and established the safety and feasibility of this technique. This review will focus on the addition of concurrent chemotherapy to radiotherapy in the definitive management of high-risk prostate cancer. PMID- 26266100 TI - Concise review on the safety of exercise on symptoms of lymphedema. AB - Lymphedema is an atypical accumulation of high-protein fluid located just beneath the skin, which often occurs in the arm or leg. Exercising with lymphedema was traditionally considered to be unsafe. However, recent research indicates that exercise may be beneficial to individuals with lymphedema. Studies indicate that exercise can improve the range of motion and strength of the afflicted limb(s), as well as overall fitness and functional quality of life, and can be performed without exacerbating symptoms of lymphedema. PMID- 26266101 TI - Is there a role for epidermal growth factor receptor tyrosine kinase inhibitors in epidermal growth factor receptor wild-type non-small cell lung cancer? AB - Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with a world-wide annual incidence of around 1.3 million. The majority of patients are diagnosed with advanced disease and survival remains poor. However, relevant advances have occurred in recent years through the identification of biomarkers that predict for benefit of therapeutic agents. This is exemplified by the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors for the treatment of EGFR mutant patients. These drugs have also shown efficacy in unselected populations but this point remains controversial. Here we have reviewed the clinical data that demonstrate a small but consistent subgroup of EGFR wild-type patients with NSCLC that obtain a clinical benefit from these drugs. Moreover, we review the biological rationale that may explain this benefit observed in the clinical setting. PMID- 26266102 TI - Isolated limb infusion chemotherapy with or without hemofiltration for recurrent limb melanoma. AB - AIM: To better define the efficacy and the safety of intra-arterial infusion performed with or without hemofiltration for recurrent limb melanoma. METHODS: Patients with the following characteristics were included in the study: recurrent limb melanoma not indicated for surgical resection, measurable disease in the extremity, > 18 years, performances status (Eastern Cooperative Oncology Group ) was 0-1 and life expectancy of at least 6 mo. Twenty nine consecutive patients were enrolled in the study. Patients underwent fluoroscopic placement of angiographic arterial and venous catheters to infuse the drug in the artery [isolated limb infusion (ILI)], and to stop the out flow (venous). Melphalan was rapidly infused into the isolated limb via the arterial catheter after the inflation of venous balloon catheter. Then the circulation of the limb was completely blocked with a pneumatic cuff at the root of the limb. Haemofiltration (HF) was available only in the main center, and was performed with an extracorporeal perfusion system, in order to reduce high systemic toxic peaks of drug. RESULTS: Thirty seven ILI were done in 29 cases (31 ILI-HF and 6 ILI) between 2001 and 2014 at Ancona and Pesaro Hospitals, Italy. Clinical outcomes were monitored 30 d after treatment. Eleven patients (38%) received infusion of melphalan alone, 7 (24%) melphalan associated to mitomicin C and 7 (24%) melphalan associated to cisplatin, the remaining 4 were treated with cisplatin, melphalan and epirubicin or cisplatin and mitomicin C. The overall response rate was 66%, in particular, 3 patients (10%) were complete responders and 16 (56%) were partial responders; whereas 7 patients (24%) had stable disease, and 3 (10%) showed progressive disease. Limb toxicity was assessed adopting Wieberdink scale, with evidence of 90% of low grade (I and II) toxicity. CONCLUSION: ILI-HF and ILI are effective and safe treatments for recurrent non-resectable limb melanoma. They present evidence of favorable clinical benefit and is effective in delaying progression. PMID- 26266103 TI - Comparative analysis of the effectiveness of abiraterone before and after docetaxel in patients with metastatic castration-resistant prostate cancer. AB - AIM: To study the efficacy and safety of abiraterone in patients with and without prior chemotherapy. METHODS: The databases including PubMed and abstracts presented at the American Society of Clinical Oncology meetings up to April 2014 were systematically searched. Eligible studies included randomized controlled trials (RCTs) in which abiraterone plus prednisone was compared to placebo plus prednisone in metastatic castration-resistant prostate cancer (CRPC) patients. The summary incidence, relative risk, hazard ratio and 95%CI were calculated using random or fixed-effects models. Heterogeneity test was performed to test between-study differences in efficacy and toxicity. RESULTS: A total of two phase III RCTs were included in our analysis, with metastatic CPRC patients before (n = 1088) and after chemotherapy (n = 1195). Prior chemotherapy did not significantly alter the effect of abiraterone on overall survival (P = 0.92) and prostate specific antigen (PSA) progression-free survival (P = 0.13), but reduced its effect on radiographic-progression-free survival (P = 0.04), objective response rate (P < 0.001), and PSA response rate (P < 0.001). Prior chemotherapy significantly increased the specific risk of fluid retention and edema (P < 0.001) and hypokalemia (P < 0.001), but decreased the risk of all-grade hypertension (P < 0.001) attributable to abiraterone. There was no significant difference of cardiac disorders associated with abiraterone between the two settings (P = 0.58). CONCLUSION: Prior chemotherapy may reduce the effectiveness of abiraterone in patients with metastatic CRPC. PMID- 26266104 TI - Second-line treatments for advanced gastric cancer: Interpreting outcomes by network meta-analysis. AB - AIM: To study the effectiveness of second-line treatments for advancer gastric cancer by application of Bayesian network meta-analysis. METHODS: Our search covered the literature up to February 2015. The following 6 treatments were evaluated: (1) irinotecan (camptothecins); (2) paclitaxel (taxanes class); (3) docetaxel (taxanes); (4) everolimus (mammalian target of rapamycin inhibitors); (5) ramucirumab (vascular endothelial growth factor receptor 2 inhibitors); (6) ramucirumab + paclitaxel. Our methodology was based on standard models of Bayesian network meta-analysis. The reference treatment was best supportive care (BSC). The end-point was overall survival. Median survival was the outcome measure along with 95% credible intervals. RESULTS: Our search identified a total of 7 randomized controlled trials. These trials included 2298 patients (in 15 treatment arms) in whom a total of 6 active treatments were evaluated as well as BSC. There were 21 head-to-head comparisons (6 direct, 15 indirect). The difference in survival between each of two active treatments (paclitaxel and ramucirumab + paclitaxel) vs BSC was statistically significant, while the other 4 showed no statistical difference. In the 6 head-to-head comparisons between active treatments, no significant survival difference was demonstrated. CONCLUSION: Our results indicate that both paclitaxel monotherapy and ramucirumab + paclitaxel determine a significant prolongation in survival as compared with BSC. PMID- 26266105 TI - Morphometrical Analysis of Developing Cochlear Ganglion Neurons: A Light Microscopic Fetal Study. AB - BACKGROUND AND AIM: The cochlear or spiral ganglion neurons are the initial bridge between the external world of sound and its discernment in the brain. As the developing human fetal cochlea is known to start functioning in mid gestational period, its anatomical details when compared with adults could vary with each gestational age. The aim of current study was to assess morphometrical parameter of developing human fetal cochlear ganglion neurons and comparison of data in each gestational period. MATERIALS AND METHODS: Ten aborted human fetuses from 14th to 28th weeks of gestation were procured from Department of Obstetrics and Gynaecology of associated hospital, after obtaining ethical clearance and were processed for studying under light microscope. Area of neurons from each gestational age was measured on histophotomicrographs using image Proplus software. Standard statistical method was used to calculate area range and percentage of small and large ganglion neurons. RESULTS: The neuronal area increased progressively in successively higher gestation age fetuses. In the fetus belonging to lowest gestational age the area ranged from 4-37MUm2 while in highest gestational age fetus its range was 10-58.3MUm2. The small ganglion neurons were higher in 14 weeks (65.5%) fetuses and 16-20 weeks (81.03%) fetuses, while in higher gestational age fetuses' large ganglion neuronal population was higher (62-66%). CONCLUSION: A baseline morphometrical representation of fetal cochlear ganglion neurons could be of relevance in advanced human experimental studies on effect of neurotrophic factors in human fetuses with congenital deafness. It has been found that these factors directly influence neuronal maturation assessed by progressive increase in soma size and survival. PMID- 26266106 TI - Body Donation after Death: The Mental Setup of Educated People. AB - INTRODUCTION: Without dissection of cadavers teaching and learning of anatomy is nearly difficult; there remains a gap between the practical knowledge and the gathered theoretical knowledge. But there is a scarcity in the availability of the donated bodies for the sake of medical education. On the other hand a large number of people in our country are in waiting list for organ transplantation which could be overcome by deceased organ donation. AIM: Aim of the study was to evaluate the awareness regarding body donation after death. MATERIALS AND METHODS: A cross-sectional study was conducted among medical students, engineering students and doctors in Indian population. Total 300 participants were answered the questionnaire providing information about the knowledge and attitude towards body and organ donation. RESULT: 46.33% of entire study group had strongly positive attitude about cadaveric organ donation and 17% had no idea about this. 18% of total participants were unwilling for body donation after death. CONCLUSION: The present study has been done elaborately to find out the different barriers for body or organ donation. It is clear from the study that though there is high level of awareness, nobody has filled up the pledge form till now. It indicates that there is a gap between the knowledge and motivation for organ and body donation after death which has to be overcome by proper guidance and education. Media and other voluntary organisations could take an important role for this purpose. PMID- 26266107 TI - Variation in Tendinous Intersections of Rectus Abdominis Muscle in North Indian Population with Clinical Implications. AB - AIM OF THE STUDY: Incisions through the abdominal wall are based on anatomical principles and Rectus abdominis muscle provides an excellent myocutaneous flap. The present work was proposed to identify variations in numbers and location of tendinous intersections of the Rectus Abdominis muscle in the cadavers as a guide to the surgical procedures. MATERIALS AND METHODS: The study was conducted on 54 cadavers of North Indian origin allotted to undergraduate medical student for Anatomy dissection classes. Manual dissection was done to identify tendinous intersections of the Rectus Abdominis muscle with reference to number and location. RESULTS: In the present study one cadaver had five tendinous intersections (1.85%), one cadaver had four tendinous intersections (1.85%) and 52 cadavers had three tendinous intersections (96.29%). CONCLUSION: The present study is an effort to provide data about the anatomical variation in numbers and location of tendinous intersections of the Rectus Abdomini muscles. Rectus abdominis muscle provides an excellent myocutaneous flap because the muscle belly is separated from surrounding tissue within the rectus sheath. This study is representative of a small study of the human population and only serves to illustrate the variations in the anatomy of the tendinous intersections. More extensive studies are required to establish a definitive pattern among local populations to serve as a guide for surgical procedures. PMID- 26266108 TI - Aberrant Dual Origin of the Dorsal Scapular Nerve and Its Communication with Long Thoracic Nerve: An Unusual Variation of the Brachial Plexus. AB - Pre and post-fixed variations at roots of the brachial plexus have been well documented, however little is known about the variations that exist in the branches which arise from the brachial plexus. In this paper, we describe about one such rare variation related to the dorsal scapular and the long thoracic nerve, which are the branches arising from the roots of the brachial plexus. The variation was found during routine dissection. The dorsal scapular nerve, which routinely arises from the fifth cervical nerve root (C5), was seen to receive contributions from C5 as well as sixth cervical nerve (C6), while the long thoracic nerve arose from C6 and seventh cervical nerves (C7) only. Furthermore along with variations in origin of the dorsal scapular and long thoracic nerves, the brachial plexus was seen to exist as a prefixed plexus receiving a contribution from C4 nerve root. An aberrant communicating branch between the dorsal scapular and long thoracic nerve was also identified. Knowledge about the course and anatomy of such variations can be vital for understanding the aetiology of various conditions such as winging of scapula, interscapular pain, administration of cervical nerve blocks, surgeries and for effective management of regions and muscles supplied by dorsal scapular and long thoracic nerve. PMID- 26266109 TI - The Ossified Bifid Superior Transverse Scapular Ligament Causing a Double Suprascapular Foramen: A Case Report. AB - Ossified bifid superior transverse scapular ligament causing a double suprascapular foramen is a very rare finding. This ossified ligament reduces the suprascapular space by half of its original size. It is one of the precipitating factors of suprascapular nerve entrapment. Here we describe a double suprascapular foramen in a dry left scapula of Indian origin. There were two bony bars bridging the suprascapular notch thereby making two foramina. The bony bars were 'V' shaped with its apex attached to the lateral side of the suprascapular notch. The upper foramen was large and triangular whereas the lower foramen was small and oval. Considering the shape of the foramen and the 'V' shaped attachment of the bony bars, we conclude it to be due to the ossification of bifid superior transverse scapular ligament. A double suprascapular foramen should always be kept in mind while diagnosing and treating suprascapular nerve entrapment. Knowledge about the double suprascapular foramen would be useful to orthopaedic surgeons who perform decompression for suprascapular nerve entrapment through arthroscopy and open procedures. PMID- 26266110 TI - Variant Branching Pattern of Superior Thyroid Artery and Its Clinical Relevance: A Case Report. AB - Thyroid surgeries are most common neck surgeries; hence thorough knowledge of the blood supply of this gland to the surgeons is of immense importance to prevent any alarming haemorrhage. We report a rare unilateral branching pattern of superior thyroid artery (STA) on right side during routine dissection on an adult male cadaver in the Department of Anatomy, A.I.I.M.S, New Delhi. Left superior thyroid artery was normal. The common trunk (CT) arose from anterior surface of right external carotid artery (ECA) just above the bifurcation of common carotid artery (CCA) soon dividing into five branches i.e., infrahyoid, superior laryngeal, superior thyroid, cricothyroid and sternocleidomastoid artery. This variant branching pattern of STA is very rare. The inferior thyroid arteries did not show any unusual distribution. Knowledge of such arterial variations related to the thyroid gland is immensely helpful to the surgeons to avoid damage of the vital organs in this region. PMID- 26266111 TI - Impact of Admission Time on Treatment and Outcome of Stroke in Patients Admitted to Tertiary Care Hospital: A Pilot Study from Central India. AB - INTRODUCTION: Admission of patients within window period has been linked with efficacy of treatment outcome and recovery. The present study examined the effects of early vs delayed admission on functional outcome of Acute Ischemic Stroke (AIS) as well as added value of stroke markers in such patients admitted to a tertiary care hospital in Central India. MATERIALS AND METHODS: Hundred and four patients admitted to Neurology department of Central India Institute of Medical Sciences were grouped as early referrals (within 24 hour admission) and late referrals (after 24 hour admission) based on onset of symptoms and time of admission. Baseline data, throm bolysis eligibility, hospital and long term outcomes were determined in early and later referrals. Stroke markers NSE, S-100 betabeta and ITIH4 peptides were also screened in patients who were further categorized as improved and expired /dependent during hospital outcome. Outcome of death /dependency in both groups was analysed using multivariate regression analysis. Kaplan-Meier analysis was performed to determine the rate of stroke mortality in hospital and over 12 and 15 month period. RESULTS: Hospital outcome indicated higher percentage (90%) of improved cases in early referrals as opposed to 79% observed in late referrals. Similarly, the ratio of dependency was slighter higher in late referrals (18%) as compared to early referral (6%) cases. The long term outcome at 12 and 18 months showed more or less similar ratio of death/dependency in early (23%, 9%) and late referrals (32%,24%) respectively. Multivariate analysis revealed no significant impact of risk confounders at long term and short term outcome in both groups. Analysis of stroke marker revealed better prognosis with significant association between ITIH4 peptides and NSE & S 100 betabeta level with level of improvement in early referrals. CONCLUSION: Early admission of AIS patients is associated with better hospital outcome. However admission time has no major impact on long term outcome in AIS patients. Moreover, stroke markers such ITIH4, can be used as a predictor of stroke outcome and may have prognostic importance in AIS cases in future. PMID- 26266112 TI - Erythrocyte Antioxidant Defenses Against Cigarette Smoking in Ischemic Heart Disease. AB - BACKGROUND: Cigarette smoke promotes atherogenesis by producing oxygen-derived free radicals. AIM: The present study was conducted to determine the effect of cigarette smoking on lipid peroxidation and erythrocyte antioxidant status in ischemic heart disease (IHD). MATERIALS AND METHODS: A total of 327 male subjects were enrolled for this study, divided into two groups consisting of 200 patients, who were consecutively admitted for IHD in the intensive cardiac care unit (ICCU) of a Government Hospital and 127 age matched male healthy subjects. Both the groups were subsequently categorised into smokers and non smokers sub groups depending upon the smoking history {>/= 20 pack years of smoking; (20 cigarettes per day for one year constitutes one pack year)}. All 327 subjects were investigated for lipid profile, malondialdehyde (MDA) levels and the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX). STATISTICAL ANALYSIS: The differences in the parameters between the groups were tested for significance by one way ANOVA using the SPSS software version 19. A p-value of < 0.001 was considered to be significant statistically. Multiple comparisons were made between all the four groups by Post Hoc Tukey test. RESULTS: There was highly significant difference (p<0.001) observed in GPX activity, in comparison to CAT and SOD (p=0.032, p=0.009) between smokers vs non smokers in control group as well as patient group. The plasma MDA levels were found to be increased significantly (p<0.001) in IHD patients, who smoked as compared to those who did not. CONCLUSION: Chronic smoking enhances erythrocyte lipid peroxidation in IHD patients with concomitant failure of both plasma and erythrocyte antioxidant defense mechanisms. Along with conventional lipid markers and plasma MDA levels, the erythrocyte GPX activity was observed to be a better marker of oxidative stress, in chronic smokers, who are at risk of developing IHD. PMID- 26266113 TI - Effect of Sub Maximal Dynamic and Static Exercises on QTc interval in Healthy Young Men. AB - INTRODUCTION: The QTc interval depends largely on cardiac repolarization since the duration of cardiac depolarization is fairly constant in the normal heart. QTc at rest as well as during exercise has many clinical implications. In this study, we have compared the relative effects of dynamic and static exercise on QTc. AIM: To measure QTc interval in young men at rest and also assess how it is further modulated by submaximal dynamic and static exercises. MATERIALS AND METHODS: This observational study was conducted in the Department of Physiology on 30 non-obese young men randomly selected from the students of our institute after obtaining the consent and institutional ethical clearance. Continuous blood pressure monitoring and ECG recording was done in the subjects. Baseline (pre exercise), post submaximal dynamic (Harvard's step test) and post submaximal static exercise (hand-grip exercise) recordings of ABP and ECG were taken for analysis. The measured QT interval was corrected for heart rate using the formula of Bazett et al., {QTc=QT/RR(1/2)}.Statistical analysis was done using Graph pad Prism 5 software (California, USA). The baseline and post-exercise data were compared using paired t-test. A p<0.05 was taken to be statistical significant. RESULTS: There were statistically significant increases in HR, SBP, DBP and QTc interval after dynamic exercise in comparison to the baseline values (p<0.05). Significant increase in HR (p<0.05) with no significant change in QTc and other cardiovascular parameters were recorded following static exercise (p>0.05). CONCLUSION: Significant increase in QTc interval was observed after dynamic exercise, however, no change in QTc was observed following static exercise, and hence we conclude that static exercises may not be useful in assessing the cardiovascular status of an individual or in predicting cardiovascular events. PMID- 26266114 TI - Fibrinolytic Activity of Blood and its Determinants in Healthy Medical Students. AB - BACKGROUND: Decreased fibrinolytic activity results in longer fibrinolysis time of blood and an increased propensity for hypercoagulable states of blood. Subjects with less fibrinolytic activity are prone to coronary artery disease, stroke and thromboembolic phenomena. AIM: The study aims to identify the impact of gender, dietary habits, body mass index, physical activity level and menstrual cycle on fibrinolytic activity in healthy subjects. SETTINGS AND DESIGN: Cross sectional study on randomly selected 206 healthy medical students aged 17 to 23 years. MATERIALS AND METHODS: Anthropometric measurements, dietary habits, physical activity level and menstrual history were obtained. Fibrinolysis time of fasting venous blood sample was determined by Euglobulin Lysis Time (ELT) method. RESULTS: Highly significant gender difference was noted in mean fibrinolytic activity (p=0.002). Mean fibrinolytic activity also showed a significant relationship with BMI (p=0.001) and with different phases of menstrual cycle in females (p=0.004). However, such relationship was not observed with diet and physical activity (p>0.05) in boys and girls. CONCLUSION: Gender difference, body mass index and menstrual cycle phases have influences on the fibrinolytic activity of blood. This might be due to cyclical changes in the sex hormones levels, endometrium-derived plasmin and plasminogen activators and excess production of plasminogen activator inhibitor type-1 (PAI-I) in visceral adipocytes. PMID- 26266115 TI - Effect of Yoga Practice on Levels of Inflammatory Markers After Moderate and Strenuous Exercise. AB - BACKGROUND AND OBJECTIVES: To evaluate the effect of yoga practice and exercise challenge on Tumour Necrosis Factor alpha (TNF-alpha), Interleukin-6 (IL-6) levels and lipid profile. MATERIALS AND METHODS: Two hundred and eighteen subjects participated in the study. One hundred and nine volunteers (51 males and 58 females) in the age group of 20 to 60 years, who practiced yoga regularly for over five years for a period of one hour daily, performed a bout of moderate exercise and a bout of strenuous exercise as per Standardized Shuttle Walk test protocol. Anthropometrically matched, age matched and gender matched subjects, who did not practice yoga (non-yoga group) were chosen as controls (non-yoga, n=109). The non-yoga group also performed similar exercises. The blood samples of both the groups were collected before and after the exercises. TNF-alpha and IL-6 was analysed before and after the exercise by Sandwich ELISA (Enzyme Linked Immunosorbent Assay). RESULTS: Resting plasma TNF-alpha concentration was significantly higher in non-yoga group when compared to yoga group (p<0.05). There was an increase in TNF-alpha levels in both the groups in response to strenuous exercise. There was no gender difference in TNF-alpha and IL-6 levels before and after exercise in yoga and non-yoga groups. CONCLUSION: Regular practice of yoga lowers basal TNF-alpha and IL-6 levels. It also reduces the extent of increase of TNF-alpha and IL-6 to a physical challenge of moderate exercise and strenuous exercise. There is no significant gender difference in the TNF-alpha and IL-6 levels. Regular practice of yoga can protect the individual against inflammatory diseases by favourably altering pro-inflammatory cytokine levels. PMID- 26266116 TI - Role of Perceptual Factors on Endurance Profiles on Treadmill Exercise. AB - CONTEXT: It is common practice to unravel signs of possible cardiac ischemia by exposing the heart to graded degrees of exercise stress on treadmill under close monitoring and terminating it at safe limit. The safe limit of exercise duration and intensity is based on subjects who report a sense of exhaustion or appearance of any defined adverse sign whichever is earlier. Commonly, endurance is determined by subjective perception of distress leading to discontinuation of exercise. AIM: Scope of favourable manipulation of perception of stress was evaluated to extend the duration of exercise, and thereby the endurance. MATERIALS AND METHODS: The indices of endurance such as duration of exercise, the distance covered and equivalents of O2 consumption (METs) as well as Cardiovascular adaptational changes of 30 young healthy male medical students are compared between two sets of conditions; {1} Routine treadmill exercise without intervention (Mode A) and later {2} same exercise repeated with individualized musical experience to favourably distract the perception of stress (Mode B). RESULT: It has been conclusively demonstrated that perceptual modification of stress in Mode B caused significant improvement in endurance profiles, reflected by sustenance of longer duration of exercise, correspondingly greater cumulative distance covered and greater METs. Cardiovascular parameters of heart rate and blood pressure rise are comparatively less in Mode B, though not significant. The extent of cardiac stress evaluated by Rate-Pressure (R-P) product is also lesser spite of longer duration of exercise, pointing to better cardiovascular adaptational changes under states of perceptual modification (Mode B). CONCLUSION: Its relevance to day-to-day physical activities including exercise is obviously to make them enjoyable, rather than monotonous, for maximal benefit to health and endurance. PMID- 26266117 TI - Inflammation During Gestation Induced Spatial Memory and Learning Deficits: Attenuated by Physical Exercise in Juvenile Rats. AB - BACKGROUND: Gestational infections induced inflammation (GIII) is a cause of various postnatal neurological deficits in developing countries. Such intra uterine insults could result in persistent learning-memory disabilities. There are no studies elucidating the efficacy of adolescence exercise on spatial learning- memory abilities of young adult rats pre-exposed to inflammatory insult during fetal life. AIMS AND OBJECTIVES: The present study addresses the efficacy of physical (running) exercise during adolescent period in attenuating spatial memory deficits induced by exposure to GIII in rats. MATERIALS AND METHODS: Pregnant Wistar dams were randomly divided into control and lipopolysaccharide (LPS) groups, injected intra peritoneally (i.p) with saline (0.5ml) or lipopolysaccharide (LPS) (0.5mg/kg) on alternate days from gestation day 14 (GD 14) till delivery. After parturition, pups were divided into 3 groups (n=6/group) a) Sham control and LPS group divided into 2 subgroups- b) LPS and c) LPS exercise group. Running exercise was given only to LPS exercise group during postnatal days (PNDs) 30 to 60 (15min/day). Spatial learning and memory performance was assessed by Morris water maze test (MWM), on postnatal day 61 to 67 in all groups. RESULTS: Young rats pre-exposed to GIII and subjected to running exercise through juvenile period displayed significant decrease in latency to reach escape platform and spent significant duration in target quadrant in MWM test, compared to age matched LPS group. Results of the current study demonstrated that exercise through juvenile/adolescent period effectively mitigates gestational inflammation-induced cognitive deficits in young adult rats. CONCLUSION: Inflammation during gestation impairs offspring's spatial memory and learning abilities. Whereas, early postnatal physical exercise attenuates, to higher extent, cognitive impairment resulted from exposure to LPS induced inflammation during intrauterine growth period. PMID- 26266118 TI - Fungal Culture Positivity in Patients with Perforation Peritonitis. AB - BACKGROUND: Perforation peritonitis is the most common surgical emergency. A large number of microorganisms have been cultured from the abdominal fluid obtained from patients with gastrointestinal perforation peritonitis. The present study was undertaken to determine the frequency of positive fungal culture in perforation peritonitis as Candida co-infection is reported to be a bad prognostic factor in these patients. MATERIALS AND METHODS: The intraoperative specimens of abdominal fluid collected during laparotomy from 140 consecutive patients of gastro-intestinal perforation were analysed by microbial culture for bacteria and fungi. Their antimicrobial susceptibility was also studied. RESULTS: The mean presenting age of the patients was 35 years and 120 (85.7%) of them were males. Aerobic Gram Negative Bacilli (AGNB) were observed in 82 (79.6%) of the culture positive abdominal fluid specimens, of which 58 (70.7%) were Escherichia coli. Gram negative bacteria were most frequently isolated from colorectal perforation (100%) while Gram positive bacteria were from upper gastrointestinal perforation (47.2%). Candida was cultured in as many as 68 of 140 (48.6%) specimens. Its prevalence was highest in patients with gastroduodenal perforation (70.5%) and was altogether absent in patients having appendicular perforation. CONCLUSION: High prevalence of fungal culture positivity of peritoneal fluid of patients of perforation peritonitis shows that along with the bacterial culture, fungal cultures should always be asked for in such patients. Adequate and timely antimicrobial treatment including treatment of fungal infection could help reduce mortality in this group of patients. PMID- 26266119 TI - Molecular Characterization and Resistant Spectrum of Enterococci Isolated from a Haematology Unit in China. AB - OBJECTIVES: The present study screened clinical isolates of E. faecalis and E. faecium to determine resistant spectrum and the potential virulence genes characterization among them of haematology patients. METHODS: Clinical Enterococci isolates were obtained from a haematology unit in a tertiary care hospital in China. RESULTS: Among 125 isolates available for the investigation, 46 were identified as E. faecium, and 79 were E. faecalis. Urine was the most common source (82, 65.6%). E. faecium isolates were more resistant than E. faecalis. Among E. faecium, maximum resistance was seen against PEN 93.5% and AMP 93.5% followed by CIP 87%. Eight vancomycin-resistant E. faecium (VREfm) isolates were obtained, positive for vanA genotype. Of 125 Enterococci isolates, 67(53.6%) were acm, and 42.4%, 25.6%, 25.6%, 24.8%, 23.2%, 20.8%, 10.4% and 7.2% of isolates were positive for esp, cylL-A, asa 1, cylL-S, cpd, cylL-L, gel-E and ace, respectively. E. faecalis isolates have more virulence genes (VGs) than E. faecium. MLST analysis of VREfm identified three different STs (ST17, ST78 and ST203). CONCLUSION: The study provides the molecular characterization and resistant spectrum of Enterococci isolated from a haematology unit in China. Molecular analysis showed that all VREfm isolates belonged to pandemic clonal complex-17(CC17), associated with hospital-related isolates. Therefore, determining resistant spectrum and virulence characterization is crucial for the prevention and control of the spread of nosocomial infections caused by Enterococci in the haematology unit. PMID- 26266120 TI - Prevalence of MLSB Resistance and Observation of erm A & erm C Genes At A Tertiary Care Hospital. AB - BACKGROUND: The increasing resistance to macrolide, lincosamide, streptogramin B (MLSB) agents among Staphylococcus aureus is becoming a challenge to microbiologist. Clindamycin has been a useful drug for treatment of infection caused by the staphylococcus aureus, but change in clindamycin sensitivity pattern due to various mechanisms is leading to therapeutic failure. One of the important mechanisms is mediation of resistance by erm genes. Staphylococcus strains which have erm genes show inducible clindamycin resistance that cannot be determined by routine disk diffusion test resulting in treatment failure. AIM: This study was aimed to detect the prevalence of MLSBi and MLSBc resistance and observation of erm A & erm C genes among MLSBi isolates. MATERIALS AND METHODS: A total 500 Staphylococcus aureus were isolated; they were checked by disk induction test (D- Test). Those isolates which showed inducible clindamycin resistance were randomly selected and subjected to PCR for the observation of erm A and erm C genes. RESULTS: Prevalence of MLSBi and MLSBc isolates were almost similar that is 10.8% and 11.6% respectively. MLSBi isolates showed more resistance to drugs when compared to MLSBc isolates. Neither of MLSBi and MLSBc isolates was resistant to Vancomycin and Linezolid. Inducible clindamycin was mainly due to presence of erm A gene. CONCLUSION: D- test should be mandatory at every microbiology laboratory and should be used in routine antibiotic procedure which will minimize the misuse of drug ultimately minimize the risk of treatment failure. PCR should be performed for the detection of genes responsible for erythromycin resistance as it is a quick and most sensitive method. PMID- 26266121 TI - Necrotizing Fasciitis of Hand By Methicillin Resistant Staphylococcus aureus (MRSA) - A Sinister. AB - Necrotizing fasciitis (NF) is an aggressive and life-threatening infection of skin and soft tissue characterized by widespread fascial necrosis, leads to gross morbidity and mortality if left untreated. Although MRSA has become a common isolate associated with skin and soft tissue infections globally over the past few years, monomicrobial MRSA NF has been reported only in a few studies. Our case represents the development of NF followed by trivial trauma salvaged with daptomycin and amputation of the affected limb. Prompt diagnosis and surgical management with empiric MRSA cover in areas where community acquired MRSA (CA MRSA) is endemic for suspected cases of necrotizing fasciitis can prevent the dreaded consequences. PMID- 26266122 TI - Biofilm Production Correlating with Multidrug Resistance Among Clinical Isolates of Acinetobacter baumannii. PMID- 26266123 TI - Antifungal Breakpoints of Non-albicans Candida Clinical Isolates in Vitek-2 Compact. PMID- 26266124 TI - Giant Platelets in Platelet Donors - A Blessing in Disguise? AB - INTRODUCTION: Inherited thrombocytopenias, including inherited giant platelet disorders (IGPD) are relatively rare, but their prevalence is probably underestimated. Harris platelet syndrome, the most common IGPD reported from Indian subcontinent, mostly from eastern part, is characterised by a low platelet count, high mean platelet volume (MPV) and absence of bleeding. AIM: A short study was conducted to assess the prevalence of giant platelets in voluntary donors of single donor platelets (SDP) and analyse the effect of transfusion of such SDPs in patients. MATERIALS AND METHODS: Voluntary donors of SDPs were screened as per standard guidelines prior to the procedure. A complete blood count (including MPV) along with a peripheral smear was done. A total of 45 donors were screened for plateletpheresis. Following plateletpheresis from these donors, a platelet count from the collection bag was done after one hour. The SDP was transfused as a single unit or divided into two and transfused to the same patient at two different occasions, as per clinical need. Platelet counts on pateints were done after one hour and the platelet recovery was noted. RESULTS: Out of the 45 donors who were screened, 30 (66.67%) were found to have giant platelets. It was observed that the pre procedure platelet counts in donors having giant platelets were relatively low (1.5 -1.7 lacs) and so also the platelet yield (2.7-3x10(11)) compared to donors who did not, but the post transfusion platelet recovery was greater. CONCLUSION: Since presence of giant platelets has been seen to be common in the Eastern part of India, a peripheral smear examination should always be considered during screening of plateletpheresis donors to avoid rejecting donors with giant platelets whose platelet counts are given falsely low by autoanalysers. PMID- 26266125 TI - Helicobacter pylori Associated Gastritis in Northern Maharashtra, India: A Histopathological Study of Gastric Mucosal Biopsies. AB - INTRODUCTION: Helicobacter pylori (H.pylori) are of major concern today because of its causal relationships with gastrointestinal diseases. It represents one of the most common and medically important infections worldwide. H.pylori plays a key role in the aetiology of chronic gastritis, duodenal ulcer, gastric carcinoma and MALT lymphoma. There is paucity of literature regarding the morphological changes in H.pylori associated gastritis. AIM: We undertake this study to find out the association and prevalence of H.pylori associated gastritis by histopathological methods in North Maharashtra, India. MATERIALS AND METHODS: A total 310 patients with various upper gastrointestinal disorders were included in this study over the period of 19 months from July 2013 to January 2015. The detailed clinical history was taken and patients were subjected to video gastroscopy. Each biopsy was studied with Haematoxylin and Eosin/Giemsa method. RESULTS: The prevalence of H.pylori was high in third to fourth decades. Out of 310 patients of gastrocopy, 144 were H.pylori positive by Haematoxylin and Eosin/Giemsa method. Morphological changes specific for H.pylori was noted as atrophy and irregular gastric mucosa, lymphoid aggregates and reactive atypia. Male patient were outnumbered by female patients. CONCLUSION: Histopathological evaluation is the gold standard for diagnosing H.pylori infection. Prevalence of H.pylori in the present study was 46.5% in patients undergoing videogastroscopic biopsies for gastritis and vague upper gastrointestinal symptoms. Furthermore and large scale studies are required to establish the diagnostic modalities for H.pylori associated gastritis to prevent morbidity and mortality. PMID- 26266126 TI - Diagnosis of Salivary Gland Lesions By Fine Needle Aspiration Cytology and Its Histopathological Correlation in A Tertiary Care Center of Southern India. AB - BACKGROUND: Salivary glands may enlarge either due to inflammation or neoplastic conditions and the diagnosis is possible by fine needle aspiration cytology (FNAC). AIM: The present study was undertaken to determine utility of FNAC in the diagnosis of salivary gland lesions. MATERIALS AND METHODS: In this retrospective study, a total of 186 FNACs of salivary gland lesions were retrieved and evaluated. Of these, 146 cases had follow-up histopathological diagnosis. FNAC diagnoses were compared to histopathological diagnoses. RESULTS: The parotid glands were more commonly involved than others. Among the various diagnostic categories used in FNAC reports, Non neoplastic category was seen in 24 (16.4%), benign category in 86 (58.9%) and malignant category in 30 (20.6%) and unsatisfactory category in 6 (4.1%) of 146 cases. The overall sensitivity, specificity, accuracy, positive predictive value and negative predictive value of FNAC in the diagnosis of salivary gland lesions were 86.6%, 94.6%, 93.6%, 88.3%, and 94.6% respectively. CONCLUSION: The present study concluded that FNAC in the diagnosis of salivary gland lesions is highly sensitive, specific and accurate method. Hence, FNAC is a useful, quick and reliable diagnostic tool. It also appears to be a safe, cost effective and minimally invasive procedure, which provides information for management of salivary gland lesions. PMID- 26266127 TI - Spectrum of Oral Lesions in A Tertiary Care Hospital. AB - AIM: The present study was undertaken to study the spectrum and pattern of various oral cavity lesions in a tertiary care hospital in Rohilkhand region of Uttar Pradesh, India. BACKGROUND: Oral cavity is one of the most common sites for tumour and tumour like lesions especially in males. It has been observed that benign lesions are more common than malignant ones. MATERIALS AND METHODS: A retrospective study was carried out in a tertiary care hospital during the period of two years from June 2012 to May 2014. The study included 133 cases of oral cavity lesions. The parameters included in the study were age, gender, site of the lesion and histopathological diagnosis. Special stains and Immunohistochemical markers were applied as and when required. Data collected were analysed. RESULTS: A total of 133 cases were included in the present study. The age ranged from 8 to 80 years. Males were affected more often than females with a Male: Female ratio of 3.3:1. The most common involved site was tongue 39 (29.32%) followed by tonsil in 30 (22.56%), buccal mucosa 27(20.32%), floor of mouth 14 (10.53%), palate 12(9.02%), lower lip 8 (6.02%), upper lip 2(1.50%) and vestibule in 1 (0.75%) cases. Of the 133 cases, 63 cases (47.36%) were malignant, 52 non-neoplastic (39.10%) and 18 cases (13.53%) of benign neoplasias. The various lesions included - Squamous cell carcinoma, Verrucous carcinoma, Carcinoma-in-situ, Leukoplakia, Fibroma, Lipoma, Squamous cell papilloma, Lymphoid hyperplasia, Pseudoepitheliomatous hyperplasia, Haemangioma, Schwannoma, Atypical Pleomor -phic adenoma, Pleomorphic adenoma, Epidermal cyst, Retention cyst, Parasitic infestation, Tubercular pathology, Granulation tissue, Chronic Sialadenitis and Chronic non-specific inflammatory pathology. A larger epidemiopathological study in this region needs to be carried out for detailed statistical analysis. CONCLUSION: Benign lesions were the predominant pathology. Squamous cell carcinoma was the commonest malignant lesion. Histopathological typing of the lesion is mandatory to confirm or rule out malignancy and is essential for the rational management thus avoiding mutilating surgery. PMID- 26266128 TI - Lymphomas in Ile-Ife, Nigeria: Immunohistochemical Characterization and Detection of Epstein-Barr virus Encoded RNA. AB - BACKGROUND: The proper histopathological characterization of malignant lymphomas requires the use of immunohistochemistry along with other molecular pathology techniques. MATERIALS AND METHODS: Malignant lymphomas histologically diagnosed in our hospital were reclassified according to the WHO scheme using immunohistochemistry while in-situ hybridization was performed for the detection of Epstein-Barr virus encoded RNA. RESULTS: There were 83 cases of lymphoma. The male to female ratio was 1.9:1 while the overall mean age was 41.7 years. Non Hodgkin lymphomas (NHL) constituted about 79.5% of cases. The majority of cases (98.8%) were B-cell lymphomas. Nine subtypes of lymphomas were identified with diffuse large B-cell lymphomas (56.4% of which were of the germinal centre type) constituting the largest group (47.0%). Intermediate and high grade subtypes were more common. The majority of cases (72.3%) were nodal lymphomas with cervical lymph node being the commonest site (48.2%). Only classical Hodgkin lymphoma (HL) (20.5%) was seen of which the mixed cellularity subtype was the most common. Epstein Barr virus (EBV) encoded ribonucleic acid was detected in 7 cases (8.4%) including 4 cases of HL, 2 cases of Burkitt lymphoma and the only case of plasmablastic lymphoma. About five cases were reclassified as non-lymphoid malignant lesions. CONCLUSION: Immunohistochemistry is vital to the proper classification of lymphomas even in a resource poor environment. Although nine subtypes of lymphomas were identified, diffuse large B-cell lymphomas formed the largest single group. Epstein-Barr virus probably plays an important role in lymphomatogenesis in this environment. A larger multicentre study is required to prove this. PMID- 26266129 TI - Intramuscular Hibernoma: A Rare Tumour in Buttock. AB - Hibernomas are benign tumours of brown fat that does not recur after complete excision. These tumours are found most often in adults and most commonly in thigh. Four morphologic variants of hibernoma are identified: typical, myxoid, spindle cell, and lipoma-like. The most common histologic type is typical variant. In this report, we present the clinical, morphological features and discuss the differential diagnosis of a typical variant of intramuscular hibernoma. PMID- 26266130 TI - Non Functional Unilateral Adrenal Myelolipoma, A Case Report. AB - Adrenal myelolipoma is characterized by presence within the adrenal gland of mature adipose tissue and active bone marrow elements. Owing to their non functional nature most cases are incidental, either at autopsy or through computer tomography scan. Occasionally the lesions attain a large size to become clinically apparent. We present a case of a 58-year-old female with mass per abdomen. Preoperative computer tomography scan of abdomen, hormonal and urine analysis showed features of non functional adrenal myelolipoma. Gross specimen consists of unilateral ovoid mass, external surface having capsule with adherent fat and areas of congestion. Microscopic examination showed well encapsulated tumour tissue composed of mature adipose tissue with major blood forming elements like myeloid, erythroid and megakaryocytic series. The diagnosis was confirmed by histopathological examination of right sided adrenalectomy specimen. PMID- 26266131 TI - Mature Mediastinal Teratoma. AB - A teratoma is a tumour with tissue or organ components resembling normal derivatives of more than one germ layer. We present a case of mediastinal mature teratoma as they have a low incidence rate. A 45-year-old female presented with right sided chest pain and paroxysmal attacks of dry cough and fever. A diagnosis of pulmonary hydatid cyst was made on computed tomography (CT) examination. Microscopic study revealed a tumour composed of elements from all the three germ layers. A diagnosis of mature mediastinal teratoma was made which is the second common site for germ cell tumours. PMID- 26266132 TI - Mixed Mucinous and Infiltrating Carcinoma Occurring in Male Breast- Study of Clinico-Pathological Features: A Rare Case Report. AB - Mucinous carcinoma is a less common histologic variant of breast cancer. Cases of mucinous carcinomas in male breast are extremely rare. Here, we describe a case of mixed mucinous carcinoma i.e. mucinous carcinoma with infiltrating ductal carcinoma component and showing apocrine differentiation in a 73-year-old man. This uncommon tumour entity has dismal prognosis and treatment depends largely on the tumour type, size, lymph node involvement and hormonal status. PMID- 26266133 TI - Evaluation of Workload and its Impact on Satisfaction Among Pharmacy Academicians in Southern India. AB - OBJECTIVE: The purpose of this study was to determine the level of workload among pharmacy academicians working in public and private sector universities in India. The study also aimed to assess the satisfaction of academicians towards their workload. MATERIALS AND METHODS: A cross-sectional study was conducted for a period of 2 months among pharmacy academicians in Karnataka state of Southern India. Convenience sampling was used to select a sample and was contacted via email and/or social networking sites. Questionnaire designed by thorough review literature was used as a tool to collect data on workload (teaching, research, extracurricular services) and satisfaction. RESULTS: Of 214 participants, 95 returned the filled questionnaire giving the response rate of 44.39%. Private sector academicians had more load of teaching (p=0.046) and they appeared to be less involved in research activities (p=0.046) as compared to public sector academicians. More than half of the respondents (57.9%) were satisfied with their workload with Assistant Professors were least satisfied as compared to Professors (p=0.01). CONCLUSION: Overall, private sector academicians are more burdened by teaching load and also are less satisfied of their workload. Revision of private universities policies may aid in addressing this issue. PMID- 26266134 TI - Clinical Assessment of Weight Gain with Atypical Antipsychotics - Blonanserin vs Amisulpride. AB - BACKGROUND: Atypical antipsychotics appear to have the greatest potential to induce weight gain. Antipsychotic-induced weight gain is the one of main cause of non-compliance and discontinuation of treatment, often resulting in the relapse of psychosis. OBJECTIVE: To compare the weight gain between amisulpride and blonanserin treatment, in persons with psychosis. MATERIALS AND METHODS: Fifty six subjects with psychosis attending psychiatry department at KR Hospital, Mysore were randomized into two equal groups. After obtaining informed consent, subjects of group I received amisulpride tablets 200 mg BD, and group II received blonanserin tablets 4 mg BD, for eight weeks. Body weight, Body Mass Index (BMI) and Waist Hip Ratio (WHR) were measured at baseline, 4 weeks and 8 weeks. RESULTS: The mean weight gain with amisulpride at 4 weeks was 2.73 kg (5.21%) and at 8 weeks was 4.34 kg (8.28%) from the baseline. The mean weight gain with blonanserin at 4 weeks was 1.77 kg (3.46%) and at 8 weeks was 3.46 kg (6.75%) from the baseline. The mean BMI increase at 8 weeks with amisulpride was 1.66 +/- 0.56 and with blonanserin was 1.34 +/- 0.77. The mean WHR increase at 8 weeks with amisulpride was 0.036 +/- 0.026 and with blonanserin was 0.029 +/- 0.020. There was statistically significant increase in weight, BMI and WHR associated with both blonanserin and amisulpride at 8 weeks. But there was no statistically significant difference in those parameters between blonanserin and amisulpride, at eight weeks. CONCLUSION: Even though there was no significant difference in the weight gain caused by blonanserin, in comparison with amisulpride, both these drugs individually caused significant weight gain at 8 weeks, which is in contrast with the earlier studies, which needs to be further evaluated. PMID- 26266135 TI - A Study on the Dispensing Pattern of Over the Counter Drugs in Retail Pharmacies in Sarjapur Area, East Bangalore. AB - BACKGROUND: Over the counter drugs (OTC) are sold without the prescription of a registered medical practitioner. There are reports that OTC drug market in India is on the rise. This is attributed to the rising cost of health care, difficulty in accessing healthcare, and an alarming tendency to self manage symptoms. The outcome of this is OTC related adverse effects, abuse, and hospitalizations. Literature on OTC is sparse. Hence this study was undertaken to evaluate the dispensing pattern of OTC drugs in retail pharmacies in Sarjapur area, East Bangalore. MATERIALS AND METHODS: The study was conducted in 3 retail pharmacies in Sarjapur area, Bangalore East. The duration of the study was for a period of 10 days from August 1st to August 10th 2014. The common complaints for which the patients frequented the pharmacies were observed and recorded .The investigator personally interviewed the patients between 6pm to 9pm, near the respective pharmacies. During this study period around 216 patients visited pharmacies without prescription. The drugs supplied to 216 patients by private pharmacies without prescription was recorded. Data was analysed by descriptive statistics using Microsoft Excel. RESULTS AND OBSERVATIONS: Most commonly dispensed OTC drugs were analgesics (26.8%). The other categories of medications dispensed were antihistamines (15.2%), antacids (14.8%), antibiotics (10%), antipyretics (7.8%), Oral contraceptive (OC pills) (5.09%) and others (20%). The commonly dispensed antibiotics were Cefadroxil (250mg) for dental infection and Levofloxacin (500mg) for upper respiratory tract infection. The most common complaint for the use of OTC drugs was pain (25%). It was noted that 55.09% of the dispensed drugs belonged to schedule H. However, 13% patients were aware regarding the harmful effects of drugs. CONCLUSION: The use of OTC drugs is alarmingly high in Bangalore East. Pharmacists have to be trained and educated regarding rationale dispensing of drugs. The need for promoting the appropriate use of drugs in the Indian health care system is important. This can be achieved through educational, regulatory and managerial strategies. PMID- 26266136 TI - Ofloxacin Induced Cutaneous Reactions in Children. AB - Cutaneous adverse effects to antimicrobials are a major health problem. Though majority of them are mild and self-limiting, severe variants like Steven Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN) are not uncommon. Ofloxacin, a fluoroquinolone widely used for the treatment of urinary tract infections, acute bacterial diarrheas, enteric fever, STDs and other soft tissue infections either as a single drug or in combination with other drugs. Earlier a case of mucocutaneous maculopapular rash with oral ofloxacin and was reported in an adult. In the present hospital set up there were few reports of such reactions to adults. Here we report three different variants of reactions associated with oral ofloxacin in chlidren. Early detection of cutaneous lesions and immediate withdrawal of the offending drug can prevent progression of such reactions to their severe variants as well as morbidity and mortality. PMID- 26266137 TI - Add-on Effect of Levetiracetam on Cognitive Activity of Carbamazepine and Topiramate Treated Healthy Rats. AB - BACKGROUND: Many antiseizure drugs are used for non-epileptic indications like bipolar disorder, anxiety, neuropathic pain, prophylaxis of migraine, etc. Cognitive problems are known with many of these agents in epileptic situations but not to that extent in other situations. The antiepileptic Levetiracetam has been shown to improve a range of cognitive abilities. OBJECTIVE: To study the effect of levetiracetam, carbamazepine, topiramate and co-administration of levetiracetam with carbamazepine and topiramate on cognition in healthy rats. MATERIALS AND METHODS: Wistar albino rats of either sex were randomly assigned to 6 groups (n=6). Treatment groups: I - Normal saline; II, III & IV- Levetiracetam (180mg/kg), Carbamazepine (50mg/kg) and Topiramate (20mg/kg) respectively; V & VI Levetiracetam + Carbamazepine and VI- Levetiracetam + Topiramate respectively orally for 21 days. Morris Water Maze was used to study the spatial learning and memory in rats and the change in Escape transfer latency (ETL) was recorded to see the effect of drugs on it. Data analyzed by ANOVA followed by Dunnett's post hoc test. RESULTS: Twenty one days drug treatment significantly increased the ETL in rats treated with Topiramate (p=0.0001) and combination of Levetiracetam and Topiramate (p<0.0001) from their baseline values. At the same time, there was significant reduction in the time spent in target quadrant in Topiramate group (p= 0.033) and the combination group of Topiramate + Levetiracetam (p=0.026). No significant change was observed in the other groups when tested for both these parameters. CONCLUSION: Topiramate causes impairment of spatial memory in healthy rats after 21 days exposure and its combination with Levetiracetam could not overcome this cognitive deficit. PMID- 26266138 TI - Mental Foramen in Prediction of Age. PMID- 26266139 TI - Ebola Virus Disease (The Killer Virus): Another Threat to Humans and Bioterrorism: Brief Review and Recent Updates. AB - Ebola virus disease (EVD) described as "one of the world's most virulent diseases" by WHO was popularly known as Ebola haemorrhagic fever in the past. It is usually considered a severe and deadly illness when humans are concerned. EVD outbreaks have shown to have a very high fatality rate ranging from 50 - 90% with a reported occurrence primarily seen near the tropical rainforests of remote villages in Central and West Africa. The virus is transmitted to people from wild animals and within the human community through human-to-human contact. Natural host for Ebola virus is not yet conclusively identified but the most probable host appears to be the fruit bats of the Pteropodidae family. Five subspecies of Ebola virus are recognized till date, with Zaire Ebola virus being the most aggressive of all varieties and recording up to 90% mortality. All Ebola forms are highly contagious and hence have been classed as Category A Priority Pathogens by WHO. Severely ill patients warrant intensive support therapy. Medical workers working in affected areas need to undertake extensive measures to prevent contracting the disease. Till date, no particular anti-viral therapy has demonstrated effectiveness in Ebola virus infection. Also, no vaccine for use in humans is yet approved by the regulatory bodies. If Ebola was actually misused as a biological weapon, it could be a serious threat. Idea behind this article is to briefly review the history and present recent updates on Ebola virus, its pathogenesis and possible hopes for treatment. PMID- 26266140 TI - The Clinical Utility of Vestibular Evoked Myogenic Potentials in Patients of Benign Paroxysmal Positional Vertigo. AB - CONTEXT: Vestibular Evoked Myogenic Potentials (VEMP) is an emerging tool to diagnose Benign Paroxysmal Positional Vertigo (BPPV). The clinical utility of VEMP has been reported only in small accord in Indian literature. AIM: To study the latency and amplitude of VEMP in patients with BPPV and compare it with that of normal subjects. SETTINGS AND DESIGN: The study included two groups. Group one (control group) were 18 normal subjects. Group two (test group) were 15 subjects with unilateral BPPV. MATERIALS AND METHODS: Those subjects who fulfilled the selection criteria based on case history and audiological assessment were taken for the VEMP recording. The VEMP response consist of positive and negative successive waves (pI-nI), with latency values in adults about 13 and 23 milliseconds respectively. STATISTICAL ANALYSIS: Data was analysed using Statistical Package for Social Sciences (SPSS) version 12 (Chicago, IL, USA). Unpaired t-test was employed to measure the statistical difference between control group and test group. RESULTS: The difference in n23 and the peak to peak amplitude between the ipsilateral and contralateral ears of the test group were statistically significant, whereas such a difference in the p13 latency turned out to be statistically insignificant. It should be noted that, out of 15 patients in the test group, five patients showed only artifact tracer recordings in both the ears which is considered as no response. The heterogeneity of the results extended from absence of VEMP to prolongation of both p13, n23; prolongation of p13 alone; and even side to side variations. CONCLUSION: Absent response from the ipsilateral ear, prolonged latency of n23 and decreased peak to peak amplitude (p13, n23), indicates the disease pathology. However, large sample size is required to draw further conclusions and to consolidate the usage of VEMP in the diagnosis of BPPV. PMID- 26266141 TI - Large Plunging Ranula Presenting as Isolated Neck Swelling: Steps in Diagnosis and Surgical Steps in Management. AB - Ranula is a salivary gland cyst which typically present as localized superficial swelling over the floor of mouth. Complex or plunging ranulas develop when the mucus extravasation extends through or around the mylohyoid muscle, deeper into the neck, and present with neck lump along with or without swelling over floor of mouth. We report a case of large plunging ranula presenting as an isolated large neck mass in a 38-year-old female patient. The steps in diagnosis and surgical steps in management of the pathology are systematically described. PMID- 26266142 TI - Ewing's Sarcoma Multifocal Metastases to Temporal and Occipital Bone: A Rare Presentation. AB - Ewing's sarcoma (ES) is a common malignant bone tumour seen to involve long bones, flat pelvic bones and ribs and vertebrae in majority of cases. Here, we present a rare case of aggressive primary ES of pelvic bones with multifocal metastases to temporal bone and occipital bone. The patient presented with facial palsy and an occipital swelling, and was referred for chemotherapy. PMID- 26266144 TI - An Unusual Traumatic Lamellar Laceration of Cornea. AB - Lamellar laceration of the cornea may occur following ocular trauma. The management of lamellar laceration will depend on whether the lacerated corneal flaps are displaced or undisplaced. We hereby report an unusual case of large traumatic lamellar corneal laceration in right eye in a 14-year-old girl presenting with diminution of vision. Slit lamp biomicroscopic examination showed partial thickness corneal flap of 11.5mm X 7mm from 11o'clock to 6 o'clock position with 3 mm superonasal displacement associated with stromal folds and shifting of inferior limbus and conjunctiva. Surgery was the appropriate option which included visualization of inferior limbus by incising conjunctiva, repositioning of displaced corneal flap and securing it with sutures. Immediate examination and proper surgical management of lamellar corneal injuries results in good visual outcome and prevention of complications like fibrous ingrowth and infection. PMID- 26266143 TI - Nasal Foreign Body, Dislodged and Lost - Can the Adenoids Help? AB - Foreign body in the nasal cavity is one of the most common paediatric otolaryngology emergencies and needs to be promptly addressed. The incidence of nasal foreign body getting dislodged secondary to unsuccessful attempts to take it out is quite high and can be potentially dangerous as it might cause fatal airway compromise. The chances of it getting impacted and retained in the nasopharynx are practical, although such cases are seldom encountered for primarily nasal foreign bodies. Nevertheless, the nasopharynx should always be looked for as a site of impaction of hidden foreign objects. Presence of enlarged adenoids could be of help as it may prevent accidental lodgement of displaced foreign body in the airway, but might also result in difficulty in locating and retrieving the foreign body because it acts as an anchor-pad with its grooves and crevasses. This report presents a rare, interesting case of a child with enlarged adenoids anchoring a metallic ring and describes the clinical presentations and relevant management of a nasal foreign body dislodged and lost in the nasopharynx. PMID- 26266145 TI - Clinical Profile of Diabetic Ketoacidosis: A Prospective Study in a Tertiary Care Hospital. AB - BACKGROUND: Diabetic ketoacidosis, a well-known and major acute metabolic complication classically occurs in young patients with type 1 diabetes. However, it may occur in patients with type 2 Diabetes Mellitus too. OBJECTIVE: Aim of this study was to look into the clinical profile, precipitating factors and clinical outcome in the patients presenting with Diabetic ketoacidosis in the Emergency of a Tertiary care hospital. DESIGN: The study was a prospective study conducted over a period of two years in Kasturba Medical College, Manipal Karnataka, India. MATERIALS AND METHODS: Clinical profile of 60 diabetic patients admitted in the Emergency with the diagnosis of Diabetic ketoacidosis were analysed. RESULTS: Out of 60 patients, 12 were of Type 1 and 48 were Type 2 Diabetes Mellitus. Mean duration of diabetes was 8.65 years. Only 14 (23.3%) patients were taking regular treatment for Diabetes Mellitus whereas 32 (53.33%) patients were on irregular treatment and eight (13.33%) were not on any treatment at all. Among 12 Type 1 Diabetic patients, six patients were freshly diagnosed to be diabetic when they presented with Diabetic ketoacidosis complication. Nausea and vomiting (63.33%) were the most common symptoms of these patients. Infections (73.33%) were the most common precipitating factor for Diabetic ketoacidosis. Mean fluid requirement on first day of therapy was 3.51 liters. Mortality of 10% was seen. CONCLUSION: Diabetic ketoacidosis is a fatal acute metabolic complication of Diabetes Mellitus with heterogeneous clinical presentation. Early diagnosis and treatment can avoid morbidity & mortality. PMID- 26266146 TI - AGE-Related Differences of Novel Atherosclerotic Risk Factors and Angiographic Profile Among Gujarati Acute Coronary Syndrome Patients. AB - CONTEXT: Although numerous risk factors have been established to predict the development of acute coronary syndrome (ACS), the risk factor profile may be different between the younger and older individuals. AIM: To analyse the frequency and pattern of atherogenic risk factors and angiographic profiles in age-stratified Gujarati patients with ACS. MATERIALS AND METHODS: ACS patients undergoing coronary angiography at U.N. Mehta Institute of Cardiology and Research, Gujarat, India between January 2008 and December 2012 were classified in to two age groups with 40y as cut-off. Patients were assessed for conventional risk factors (diabetes mellitus, dyslipidaemia, hypertension, smoking, obesity), novel risk factors (high sensitivity C-reactive protein, lipoprotein (a), homocysteine), and angiographic profiles.The statistical difference between two age groups was determined by Student's t-test for continuous variables and Chi square or Fisher's exact test for categorical variables. RESULTS: A total of 200 patients, 100 patients <=40 y of age and 100 patients >40 y of age, were evaluated. Older patients had higher frequency of hypertension (32 vs. 16%, p=0.008), while family history of coronary artery disease was more common among younger patients (19 vs. 9%, p=0.041). The incidence of diabetes, dyslipidaemia, smoking and tobacco chewing did not vary significantly between the two groups. Total cholesterol and low-density lipoprotein cholesterol levels were significantly higher in the younger group (p<0.05). Lipoprotein (a), homocysteine and high-sensitivity C reactive protein levels were comparable between two age groups. Multi-vessel coronary artery disease was more common among older group. The most commonly affected coronary artery was the left anterior descending artery among younger patients (44%) and the left circumflex artery among older patients (38.1%). CONCLUSION: Young patients with ACS had different atherosclerotic risk profile and less extensive coronary artery disease as compared to older counterparts. Emphasis should be given on diagnosis and management of major modifiable risk factors. PMID- 26266147 TI - Association of Thyroid Function with Severity of Coronary Artery Disease in Euthyroid Patients. AB - INTRODUCTION: Thyroid hormone exerts multiple effects on the heart and vascular system. Variations of free T3 have been linked to coronary artery disease. We conducted a study to observe whether there is a relationship between the variation of the serum thyroid hormone levels (TSH, FT3 and FT4) and the presence and severity of CAD in the euthyroid patients. AIM: To study association of serum TSH, FT4 and FT3 levels within the normal range with presence and severity of coronary artery disease. MATERIALS AND METHODS: A total of 100 euthyroid patients with stable angina, who underwent coronary angiography were enrolled in the study. Coronary artery disease was defined as >50% stenosis in the luminal diameter in at least one major epicardial coronary artery. The Gensini scoring system was used to define the severity of the CAD and serum TSH, FT3 and FT4 levels were measured by the chemiluminescence method. RESULTS: Single vessel disease was found in 23%, double vessel disease in 15% and triple vessel disease in 17% of patients. TSH and FT4 levels were also comparable between the groups. Normal coronary group had significantly higher mean FT3 values than triple vessel disease (p=0.004) and FT3 levels showed an inverse relation with Gensini score (Pearson's correlation =- 0.30) (p =0.002). A level of FT3 <= 2.7 predicted the severity of CAD with a 70% sensitivity and 60% specificity (area under curve (AUC): 0.755, p=0.001). CONCLUSION: In the absence of primary thyroid disease and acute coronary syndrome, the occurrence of CAD is associated with lower serum levels of FT3. FT3 and not the FT4 and TSH levels may be used as an indicator of increased risk for severe CAD. The present study clearly shows the existence of a strong association between the reduction of biologically active T3 and severity of coronary artery disease. However, low T3 state could be at first interpreted as just a biological risk factor of severe coronary artery disease; only the demonstration of beneficial effects on cardiovascular, end points of long term T3 replacement in CAD patients with low T3 state can answer this fundamental issue. PMID- 26266148 TI - Assessment of the Presence of Carpal Tunnel Syndrome in Patients with Diabetes Mellitus, Hypothyroidism and Acromegaly. AB - INTRODUCTION: Carpal tunnel syndrome (CTS) is one of the most common entrapment neuropathies of the upper limbs. It results from compromised median nerve function of the wrist that is caused by increased pressure in the carpal tunnel. Repetitive use of the hand and wrist, obesity, pregnancy, rheumatoid diseases, trauma and endocrinopathies are some of the risk factors for CTS. AIM: The purpose of this study was to find out whether patients with diabetes mellitus (DM), hypothyroidism and acromegaly have an increased incidence of carpal tunnel syndrome compared to each other and normal population. MATERIALS AND METHODS: Patients were assigned into three groups as follows: patients with type II DM n: 100, patients with hypothyroidism n:48 and patients with acromegaly n:36. In addition, 50 healthy individuals were included in the study as control subjects. Patients were asked if they had any pain, symptoms of paraesthesia and numbness. Patients with peripheral neuropathy were excluded from the study. Boston Symptom Severity Scale and Functional Capacity Scale were used to assess symptom severity and functional capacity. CTS was investigated by performing electrophysiological study for both hands. RESULTS: The incidence of CTS was significantly higher in all three groups compared to the control group (p>0.05). In addition, the incidence of CTS was significantly higher in the DM group compared to the hypothyroid and acromegaly groups (p<0.001). The incidence of bilateral CTS in the DM group was significantly higher compared to both hypothyroid and acromegaly groups and the control group (p<0.001). CONCLUSION: CTS has a higher incidence in DM, hypothyroid and acromegaly patients compared to healthy individuals. Clinicians should be careful about development of CTS in DM, hypothyroidism and acromegaly. They should adopt a multidisciplinary approach and co-operate with the psychiatrist. PMID- 26266149 TI - Hypovitaminosis D and Other Risk Factors of Femoral Neck Fracture in South Indian Postmenopausal Women: A Pilot Study. AB - BACKGROUND: Non-communicable diseases like hip fractures are a significant problem in a developing country like India. The risk factors for hip fractures vary according to local practices and the availability of preventive health care delivery systems. There is paucity of data on risk factors for hip fracture in the south Indian population. AIM: This study was undertaken to assess risk factors associated with femoral neck (FN) fracture in South Indian postmenopausal women along with subsequent one year mortality. MATERIALS AND METHODS: One hundred four postmenopausal women with FN fracture and 104 age and BMI matched controls were included. Sedative use, visual impairment and other relevant risk factors were assessed. Bone biochemistry and Bone Mineral Density (BMD) were evaluated. A telephonic interview was done at the end of one year to ascertain the well-being. RESULTS: Sedative use, visual impairment, low FN BMD and vitamin D deficiency (<20 ng/ml) were seen more in fracture subjects compared to controls (p<=0.05). At the end of one year, 20% of the fracture subjects and 5% of the controls had died (p=0.001). CONCLUSION: Risk factors identified in our study are potentially correctable, and needs special attention in an Indian context to prevent hip fractures. PMID- 26266150 TI - Retinal Hemorrhages in Severe Non-cerebral Plasmodium vivax Malaria in an Adult. AB - Malaria is the most important parasitic diseases of humans and one of the leading causes of morbidity and mortality in tropical countries. Earlier Plasmodium vivax was considered as a benign infection, but now it is recognized as a cause of severe malarial disease. It causes severe malarial disease similar to those as Plasmodium falciparum including cerebral malaria, severe anaemia, severe thrombocytopenia, hepatic dysfunction, shock, acute respiratory distress syndrome (ARDS), acute renal failure, and pulmonary oedema. Malarial retinopathy includes retinal whitening, vessel changes, retinal hemorrhages and papilledema. However, retinal hemorrhages are very rare in Plasmodium vivax infestation. Hereby, we report a case of 30-year-old man, who presented with fever with chills and diminution of vision. He was found to have Plasmodium vivax infection with retinal hemorrhages. He was treated successfully with artisunate, primaquine and doxycycline, completely recovered after one month. PMID- 26266151 TI - Multiple Amoebic Liver Abscess As Initial Manifestation in Hiv Sero-Positive Male. AB - Amoebic liver abscess is the most frequent extra-intestinal manifestation of Entamoeba histolytica infection. Immunosuppression is known to predispose to amoebic liver abscess. Although amoebic liver abscess is seen more commonly in patients of Human-Immunodeficiency virus (HIV), first presentation of HIV sero positive patient as multiple liver abscess is quite uncommon.The author reports an unusual case of multiple liver abscesses in an HIV seropositive patient. This middle aged male with history of multiple unprotected sexual encounters presented with spasmodic abdominal pain, fever, diarrhoea and weight loss along with generalised ill-health and painful liver enlargement. HIV-1 serology was found to be reactive. Imaging revealed an enlarged liver with multiple, irregular, hypoechoic foci characteristic of abscesses. Amoebic aetiology was later confirmed by percutaneous aspiration and microscopy. Administration of appropriate chemotherapeutics along with institution of antiretroviral therapy led to both clinical resolution as well as disappearance of lesions. PMID- 26266153 TI - Unusual Presentation of Dengue Fever-Cerebral Venous Thrombosis. AB - Dengue infection can present as febrile illness with thrombocytopenia, dengue shock syndrome and dengue haemorrhagic fever. Neurological manifestation of dengue infection is more predominant in endemic region. Here, we report a case with unusual neurological presentation of dengue infection. A 16-year-old boy presented with fever for two week duration, headache and double vision involving left eye for two days. He had multiple erythematous rashes all over the body on 3rd day and treated conservatively. On examination he had bilateral papilloedema, left eye restricted abduction. His investigation revealed thrombocytopenia and positive dengue serology. His MRI brain with venogram showed bilateral transverse sinus thrombosis. Hence he was diagnosed as cerebral venous thrombosis due to dehydration with underlying dengue infection. He was hydrated and managed conservatively. On 3rd day his double vision started improving. His repeat MR Venogram was done after two week duration, which revealed recanalisation of bilateral transverse sinus. PMID- 26266152 TI - A Challenging Diagnosis of Fluctuating Dyspnea: Myasthenia Gravis. AB - Isolated respiratory muscles weakness is an unusual presentation of Myasthenia Gravis (MG). We present a case of 49-year-old male with undiagnosed MG who presented with fluctuating dyspnea on exertion and at rest. There was no peripheral muscle involvement, diagnostic tests and standard electromyography was normal, and the serologic tests were negative. The repetitive nerve stimulation and Single Fiber Electromyography revealed the diagnosis of MG. Interestingly the patient did not have sufficient therapeutic response on first line agents and required immunoglobulins and corticosteroids due to respiratory muscle involvement. Since skeletal muscle weakness is a cardinal feature of MG, dyspnea may be fluctuating as in our patient causing further difficulty in diagnosis as the pulmonary function tests performed during remission may be normal. This presentation highlights the need to consider MG in the differential diagnosis of unexplained dyspnea on exertion/rest. PMID- 26266154 TI - An Unusual Case of Foreign Body Aspiration Masquerading as Pulmonary Eosinophilia. AB - Foreign body aspiration into the airways is a common occurrence in inebriated conditions, paediatric age group and or loss of cough reflex. Acute symptoms, often times are recognized and medical assistance is sought. Subtle aspirations, unrecognized and stationed for longer time in the abode of airways pose variegated clinical picture. The authors present herewith an unsuspected case of Areca nut in a middle-aged woman mimicking eosinophilic pneumonia. PMID- 26266155 TI - Which one is Worse? Acute Myocarditis and Co-existing Non-compaction Cardiomyopathy in the Same Patient. PMID- 26266156 TI - Unusual Cause of Bilateral Pleural Effusion. PMID- 26266157 TI - Efficacy of Collagen Particles in Chronic Non Healing Ulcers. AB - INTRODUCTION: Chronic foot ulcers will lead to a significant and prolonged stress to the patients. Pain and discomfort that may be acute or continuous is the usual complaint in chronic non healing ulcers that may even exacerbate with change of the dressings. The end process in any wound healing is wound contracture and scar formation. Collagen plays an important role in this stage of wound healing. Collagen particles were used in chronic non healing ulcer management to prove their efficacy when compared with conventional dressing in a study conducted by us. OBJECTIVE: To compare the healing process in non healing ulcers using collagen particles with those of conventional method of dressing (betadine). MATERIALS AND METHODS: It was a non randomized, prospective study conducted for a period of October 2012 to October 2014 in hospitals belonging to Kasturba medical college. Non concurrent pre and post comparative study; between collagen group and conventional dressing group. A total of 110 patients with chronic ulcers were included; each group comprising 55 patients. RESULTS: There was a significant decrease in wound size with a mean difference of 37.29 in experimental group when compared to 14.29 in control group. CONCLUSION: Collagen dressing is effective in management of chronic non healing ulcers when compared to conventional betadine dressing. It heals by forming an early granulation tissue and thus reducing the length of hospital stay. PMID- 26266158 TI - Comparative Study of Prolene Hernia System and Lichtenstein Method for Open Inguinal Hernia Repair. AB - BACKGROUND: Prolene Hernia System (PHS) is a bi-layered polypropylene mesh with a connector that combines the anterior and posterior inguinal hernia repair, but still not very popular in this part of the country. Hence a prospective & randomized comparative study was undertaken to compare PHS with the already popular Lichtenstein Hernia Repair (LHR) and determine the post-operative outcome. MATERIALS AND METHODS: Total 67 inguinal hernia repairs were randomly assigned to either PHS or LHR method, and data was collected regarding various outcome measures like duration of surgery, post-operative pain, requirement of analgesia, return to normal activity, and early and late complications. RESULTS: Mean duration of surgery was significantly higher for PHS group than LHR group (65.4 min vs 51.26 min, p-value <0.0001). Significant difference was noted between the PHS and LHR group in terms of moderate to severe post-operative pain (15.15% vs 41.18%,p-value 0.018), time of requirement of analgesia (3.7 vs 4.6 days, p-value 0.024), and time to return to normal activity (2.7 vs 3.4 days, p value 0.023), all in favour of the former technique. No intra-operative complication was noted in either of the groups. 5 patients had early complications in PHS group and 6 in LHR group, but this was statistically not significant. The average time of follow-up for the study was 7.8 month, ranging from 1 to 18 months. Chronic inguinal pain was noted in 1 and 2 patients respectively in PHS and LHR group, again statistically not significant. No recurrence was noted in both the groups till the time of follow-up. CONCLUSION: PHS is a safe and better alternative to the time honored Lichtenstein hernia repair with the added advantage of strengthening whole of myopectineal orifice, and virtually eliminating any risk of recurrence. PMID- 26266159 TI - 'Tamsulosin and Darifenacin' Versus 'Tamsulosin Monotherapy' for 'BPH with Accompanying Overactive Bladder'. AB - PURPOSE: To evaluate the efficacy/safety of 'tamsulosin and darifenacin' (TD) vs. 'tamsulosin and placebo' (TP) for patients with symptomatic benign prostrate hyperplasia (BPH) with accompanying overactive bladder (OAB) symptoms. MATERIALS AND METHODS: This study included symptomatic patients of BPH with one or more of the following OAB symptoms; micturition frequency >8, nocturnal frequency > 2, urgency > 1 per 24 hour between November 2012 and February 2014. After protocol approval by ethics committee and obtaining informed consent, patients were randomly assigned to receive tamsulosin 0.4mg plus placebo (TP) (n=30) or tamsulosin 0.4 mg plus darifenacin 7.5 mg (TD) (n=30) for 8 weeks. The mean change from baseline in urinary frequency and incontinence episodes/24 hour (primary end points), and nocturnal frequency; mean change in PVR and changes in IPSS (secondary end points) were compared between groups at 0/eight week using voiding diary and ultrasonography. RESULTS: The mean change in frequency, incontinence, nocturnal frequency/24 hour and IPSS (International prostrate symptom score) were (-4.83 vs. -3.93, p=0.023), (-1.50 vs. 1.08, p=0.001), (-2.20 vs. -1.87, p<0.001) and (-7.90 vs. -6.27, p<0.001) in the TD/TP group respectively (significant). Apart from some minor side effects (12 vs. 9) all interventions appeared to be safe and well tolerated. The mean change in the PVR (Postvoid residual) was marginal (+10.84ml and -16.93) and the incidence of urinary retention was 13% and 3% in the TD and TP groups respectively (p=0.35). CONCLUSION: Treatment with tamsulosin and darifenacin for 8 weeks is an effective and safe treatment modality in select patients of BPH with accompanying OAB symptoms. PMID- 26266160 TI - Comparison of Clinical Presentation and Risk Factors in Diabetic and Non-Diabetic Females with Urinary Tract Infection Assessed as Per the European Association of Urology Classification. AB - INTRODUCTION: Diabetes has been known to cause severe complicated UTI as a result of its various changes in the genitourinary system. This study of UTI in diabetic females enables us to know the pattern of infections, their causative organisms and severity, particularly with reference to European Association of Urology (EUA) guidelines for UTI 2015. MATERIALS AND METHODS: This is a prospective single centre study done over a period of one year at Dayanand Medical College and Hospital on a total of 151 diabetic (Group A) and non-diabetic (Group B) female patients with diagnosis of UTI. A thorough history of the patients was taken which included looking for the anatomical level of infections, host risk factors; extra urogenital risk factors and nephropathy disease were assessed. All patients were adequately investigated. The UTI was classified according to the EAU classification for UTI, and an effort was made to find out the frequent class of UTI in this study group. RESULTS: A total of 151 females which included 70 diabetic (Group A) and 81 non diabetic (Group B) females were studied. The most common symptom was fever in both the groups. UTI was classified as per the EAU grades of UTI. In group A, the number of patients having severity grade from 1 to 6 were 47, 9, 4, 2, 4, and 4 respectively. The most common clinical presentation in both the groups was cystitis followed by pyelonephritis and urosepsis. In group B, the number of patients having severity grade from 1 to 6 were 66, 4, 5, 5, 0 and 1 respectively. Most common organism was E-coli, which was susceptible to most of the antibiotics. CONCLUSION: UTI in diabetic and non-diabetic female patients have different patterns. Uncontrolled diabetes was more commonly associated with severe UTI like pyelonephritis and emphysematous pyelonephritis. E. coli was most common isolate in either group, followed by klebsiella and Pseudomonas. Candida was isolated only from the diabetic population. Therefore, the most common type of UTI as per the EAU classification in both diabetic and non diabetic female was CY-1R: E. coli(a): 'simple cystitis but recurrent with susceptibility to standard antibiotics', in our study. PMID- 26266161 TI - The Impact of High Surgical Volume on Outcomes From Laparoscopic (Totally Extra Peritoneal) Inguinal Hernia Repair. AB - PURPOSE: Laparoscopic hernia repair is characterised by a steep learning curve for the surgeon, and proficiency and outcomes are dependent on experience. The aim of this study was to compare laparoscopic totally extra peritoneal (TEP) inguinal hernia repair outcomes conducted by a single surgeon as experience changed over time. MATERIALS AND METHODS: Clinical records of 100 consecutive patients who underwent laparoscopic TEP inguinal hernia repair (n=113 hernias) at Kent and Canterbury Hospital by a single laparoscopic surgeon over a four-year period were reviewed for postoperative outcomes. Outcomes were compared with a previous cohort of patients undergoing TEP repair in the preceding three years. RESULTS: One patient experienced chronic postoperative pain, but there were no recurrences, wound infections, haematomas, or conversions compared to three recurrences, three conversions to open operations, one haematoma, and one episode of postoperative pain in the preceding period. CONCLUSIONS: Laparoscopic TEP inguinal hernia repair can be further improved with surgical proficiency and high surgical volumes. PMID- 26266162 TI - Clinical and Radiological Outcome in Cases of Posterolateral Fusion with Instrumentation for Lumbar Spondylolisthesis. AB - INTRODUCTION: Lumbar Spondylolisthesis as a cause of low back pain and lower limb radiculopathy has been treated using varied surgical options. The role of laminectomy for decompression of neural elements and stabilization using instrumentation in the form of pedicle screws and rod construct has been a well established and time tested treatment modality. AIM AND OBJECTIVES: This study analyses the role of laminectomy and instrumentation in obtaining clinical and radiologically favourable outcome. MATERIALS AND METHODS: Data was analysed from the case records for the duration from January 2010 to March 2014. The study analyses the influence of lumbar decompression (laminectomy) and transpedicular instrumentation using titanium pedicle screws and intertransverse process iliac crest graft on patients with degenerative lumbar spondylolisthesis and spinal stenosis. CONCLUSION: Decompression primarily relieves radicular symptoms and neurogenic claudication whereas fusion primarily relieves back pain by elimination of instability. The addition of posterolateral instrumentation (pedicle screws) enhances the ability to obtain a solid arthrodesis. Posterolateral instrumentation enables improved functional outcome, better patient satisfaction and less back and lower limb symptomatology. This is irrespective of bony arthrodesis or pseudoarthrosis, at least in the short term follow-up. PMID- 26266163 TI - Clinico-Epidemiological Study and Treatment Outcome of Multinodular Goitre at A Tertiary Care Hospital. AB - BACKGROUND: Thyroid enlargement has been a common problem encountered in general surgical practice. Thyroid being an endocrine gland, its involvement has a diverse issue from a meagre cosmetic problem to a more concerned malignancy. AIM: This study was conducted to study the age and sex distribution along with the mode of presentation of Multinodular Goitre (MNG). The incidence of malignancy and the surgical complications in the study population were also studied. MATERIALS AND METHODS: In this descriptive study, patients diagnosed with MNG from January 2011 to July 2012 were chosen from the in-patient of our teaching hospital. One hundred such patients who qualified to undergo surgery were included in the study after a detailed history and clinical examination. Patients underwent Fine needle aspiration cytology (FNAC) for preoperative pathological diagnosis and the goitre was confirmed to be benign. Patients diagnosed with malignancy were excluded from the study. Following thyroidectomy, the thyroid specimens were subjected to histopathological examination. RESULTS: Among the 100 cases of MNG, 59% patients belonged to 3rd and 4th decade of life, 90% patients were females, 82% presented before 5yrs. The most common symptom at presentation was swelling (100%). Among the patients 80% were in euthyroid state, 19% were hyperthyroid and 1% hypothyroid. Most of the patients were treated with sub-total thyroidectomy (59%), followed by total (20%), near total (11%), and Hemithyroidectomy (10%). Following surgery complications like stridor and laryngeal oedema (3%), wound infection (2%), hypocalcemia (2%), haemorrhage (1%) and seroma (1%) were noted. On Histopathological examination (HPE) of the surgical specimen, 3% were reported to be malignant. CONCLUSION: As noted by this study, Multinodular Goitre is more common among females in the third and fourth decades. Patients can present with various complaints. MNG can present as hyperthyroid, hypothyroid but mostly in euthyroid state. The indication for surgery in patients with MNG includes cosmesis, hyperthyroidism, local compressive symptoms and most importantly malignancy. Subtotal thyroidectomy is the preferred surgery, but a trend towards total and near total thyroidectomy is noticeably replacing the old belief in subtotal thyroidectomy. PMID- 26266165 TI - Spontaneous Resolution of Non Traumatic Chronic Subdural Haematoma Despite Continued Antiplatelet Therapy: A Case Report. AB - Spontaneous resolution of traumatic chronic subdural haematoma (CSDH) has been reported in literature. However, those with non traumatic CSDH are exceedingly rare and none reported with continued antiplatelet therapy where it itself is an aetiological agent for development of non traumatic CSDH. A 50-year-old male presented to us with a non haemorrhagic cerebellar infarct with a concomitant CSDH without history of any trauma. Patient's PT/INR, Bleeding time and Clotting time were normal. Patient was started on antiplatelet therapy (Tablet Aspirin 150 mg OD) for the acute infarct. MR Brain at 1 month showed an increased size of CSDH. However patient denied surgical evacuation hence we continued conservative line of management, however we continued anti-platelet therapy with close neurological and coagulation profile monitoring that remained within normal range throughout the period of observation. CT at 5(th) month showed complete resolution of CSDH. Patient was on antiplatelet drugs throughout the period of observation. Our case argues about the role of antiplatelet therapy in patients with CSDH with contrary lesions requiring anticoagulation. PMID- 26266164 TI - A Prospective Randomized Trial of Open Wound Treatment vs Occlusive Dressings in Elective Surgical Cases with Respect to Surgical Site Infections. AB - BACKGROUND: Surgical wounds heal by primary intention in all the elective and emergency surgical procedures. Current practice is to place dressing over the closed wound before the patient leaves the sterile environment of the operating theatre. Dressing is a material applied to protect a wound and favour its healing. However, to leave wound open in direct contact to environment following any procedure by just applying some ointment on it, the so called open wound treatment is still controversial one. In the present study we have compared open wound treatment vs occlusive dressings in elective surgical cases with respect to surgical site infections. MATERIALS AND METHODS: The present study was conducted on 100 patients admitted for elective general surgery after taking written informed consent. Patients were divided randomly in to two equal groups each comprising of 50 patients. In Group A, patients had occlusive dressing till removal of stitches and in Group B, patients wounds were kept exposed to environment after the surgical procedure. RESULTS: In present study we observed total 7% of postoperative wounds were infected of all the clean and clean contaminated wounds we studied. In Group A, patients had occlusive dressing and these patients had 8% infection rate whereas in Group B patients, wounds were kept exposed to environment and these patients had 6% infection rate. CONCLUSION: It is hereby concluded that in the elective surgical cases there is no harm in leaving the wounds open postoperatively. This method not only helps in arresting the infective pathology at a lesser stage but also saves surgeon's time and patient's money. PMID- 26266166 TI - A Rare SOL of the Liver: Diagnostic and Management Dilemma. AB - Aetiology and clinical presentation of space occupying lesions (SOL) of liver are varied. It can be solid, cystic or heterogenous. Usually liver abscess presents as a symptomatic cystic SOL in a sick patient. Here, we are reporting a case of giant liver abscess presenting as simple benign cyst with corroborative image findings of simple cyst. He had significant co-morbid illness and jaundice on clinical evaluation. Liver abscess was not a differential diagnosis from clinical history. None of the haematological and biochemical parameters were suggestive of liver abscess. It was an intra-operative surprise to find such a huge liver abscess with 2 liters of pus, which was drained. We report this case because of its unusual presentation and associated findings. PMID- 26266167 TI - Intraabdominal Pseudocyst Developed after Ventriculoperitoneal Shunt: A Case Report. AB - Abdominal pseudocyst is a rare complication developing after ventriculoperitoneal shunt treatment. It is more commonly seen particularly in children. The underlying pathogenesis may be associated with repeat revisions or infections. Morphologically, it has no complete cyst wall, presenting only with a pseudocapsule among the intestinal loops, around the lower shunt tip. The principal problem appears to be the reduced peritoneal absorption capacity. The treatment is complicated and difficult. In this report, we present an 8-year-old abdominal pseudocyst case with a history of many shunt revisions. PMID- 26266168 TI - Retroperitoneal Accessory Spleen Presented As Metastatic Suprarenal Tumour- A Diagnostic Dilemma. AB - Accessory spleen may be formed during defective embryonic development. The retroperitoneal accessory spleen is a rare clinical entity and metastasis of renal carcinoma into this entity is extremely rare. We are presenting a case of a 50-year-old male patient who was admitted with complaints of left lower abdominal lump and pain. The computed tomography revealed a 7*4 cm mass at upper pole of left kidney. To rule out malignancy, we planned for surgical exploration. Suprarenal mass was densely adherent to left kidney so left nephouroureterectomy with suprarenal mass was performed. On histopathology examination left kidney showed transitional cell carcinoma with metastasis into suprarenal mass that was found to be an accessory spleen. Diagnosis was made retrospectively by histopathological observation. So this case highlights the difficulty in differentiation of these masses from malignant adrenal tumours. PMID- 26266169 TI - Do We Still Need to Perform Routine Histological Examination of Appendectomy Specimens? PMID- 26266170 TI - Prevalence; Characteristics and Management of Endometriosis Amongst Infertile Women: A One Year Retrospective Study. AB - BACKGROUND: Endometriosis appears to affect every aspect of a women's reproductive system resulting in infertility and spontaneous pregnancy loss. This study aims to find out the prevalence & clinical characteristics of endometriosis amongst infertile women. SETTINGS AND DESIGN: A Hospital based retrospective study over a period of one year. MATERIALS AND METHODS: It is a retrospective study conducted in the gynaecology department in Institute of Kidney Diseases & Research Centre; Ahmedabad from April 2012 to March 2013 amongst women with a primary complaint of infertility (Primary/Secondary).A total of 372 patients underwent diagnostic hysterolaparoscopy and of these 180 patients who had laparoscopic evidence of endometriosis was included in the study. All of these patients and their findings were analysed with respect to the clinical signs and symptoms. The outcome after appropriate management was analysed in subsequent follow up. STATISTICAL ANALYSIS: All collected data was entered into the SPSS version 20. Categorical data are expressed in frequency or percentage. Chi-Square test and Fisher-Exact test has been performed to carry out p-value for categorical data. P-value <0.05 shows statistically significant difference. RESULTS: The frequency of endometriosis among women with infertility subjected to diagnostic hysterolaparoscopy was found to be 48.38%. Statistical significant association with severity of disease was associated with symptoms like dysmenorrhea, chronic pelvic pain, restricted uterine mobility and adnexal tenderness. (p <0.01) Ultrasound finding of endometrioma with ground glas appearance also had statistical significant association with staging of disease (p <0.01). CONCLUSION: Endometriosis amongst infertile women is increasingly being detected due to greater use of laparoscopy in evaluation of infertility.Though most signs do not correlate with severity of disease however the presence of restricted uterine mobility, adnexal tenderness & chronic pelvic pain should always raise the suspicion of endometriosis. Laparoscopy remains the gold standard for diagnosing and staging endometriosis. PMID- 26266171 TI - Uranium-Toxicity and Uranium-Induced Osteosarcoma Using A New Regimen and Surgery : A First-Time Experience. AB - Uranium isotopes have always been problematic to mankind since many centuries. Different studies all over the world have been unable to reveal causal relationship between uranium and its toxic effects on kidneys, bone and lungs. In this case report, we present a rare association of uranium toxicity with renal dysfunction and possibility of induction of osteosarcoma by an unknown mechanism. The presentation of the 12-year-old patient was reduction in urine output along with joint pains, seemed like that of diabetes mellitus, as he was already on insulin. The patient later diagnosed to have uranium toxicity. This case is an instance of strong association between medicine and public health. With complete history, physical examination and required investigations, all common causes like NSAID toxicity, aminoglycoside toxicity and exacerbation of diabetes were ruled out. Uranium investigations were done lastly based on the toxicology report of drinking water (South African toxicologist, Caron Smith). In the management strategy, the new regimen CBMIDA, supported by studies in Europe, was used. However, to our surprise, joint symptoms tracked their way to a diagnosis of osteosarcoma, which was later operated upon by our orthopaedic surgery team. Histopathologically, it was found to be a chondroblastic type of osteosarcoma. PMID- 26266172 TI - Two Pelvic Digits on Same Side: Double Trouble? AB - Pelvic digit is a rare congenital anomaly of pelvis usually discovered incidentally on plain radiography. It usually develops in the soft tissue adjacent to the normal skeletal tissue. Its importance lays in its differentiation from heterotopic ossification, osteochondroma, Fong's disease and traumatic avulsion injuries of pelvis to avoid any unnecessary investigations and interventions. Here, we report a 32-year-old male presenting with complain of pain in right hip, was subjected to radiographic examination and two pelvic digits were noticed arising from the iliac bone in addition to features of osteoarthritis of hip joint. The symptomatology was attributed to osteoarthritis of hip after thorough physical examination and imaging investigations. PMID- 26266173 TI - Jumbo Cutter for Removal of A Bent Femoral Interlocking Nail: A Cost Effective Method. AB - Closed diaphyseal femoral shaft fractures can be treated with multiple surgical options. It is more challenging to remove a bent nail than a broken one because it is difficult to retrieve the bent nail through the intramedullary canal. Various authors have published their techniques for removal of bent femoral interlocking nail. This article describes a simple technique using Jumbo cutter for sectioning and removal of bent interlocking nail. This technique will help orthopaedic surgeons to remove bent nail without using any specialised metal cutting instruments. PMID- 26266174 TI - Sacral Agenesis with Neurogenic Bladder Dysfunction-A Case Report and Review of the Literature. AB - Sacral agenesis (part of the caudal regression syndrome) is a rare and severe sacral developmental abnormality. It is a congenital malformation of unknown aetiology with possible involvement of genetic and teratogenic factors. It is described by various degrees of developmental failure, the most extreme and rare being sirenomelia or mermaid syndrome. The associated malformations comprise anorectal, vertebral, urological, genital, and lower limb anomalies. Approximately 15-20% mothers of these children have insulin dependent diabetes mellitus. The case is being reported for its rarity and educative value because prognosis is good in isolated sacral agenesis. PMID- 26266175 TI - Clinico-radiological Approach to a Rare Case of Early Clavicle Tuberculosis: A Case Discussion Based Review of Differential Diagnosis. AB - A patient of 41 years of age presented with insidious onset atraumatic swelling arising from medial end of right clavicle with apparently normal radiograph. Initial computed tomography ascribed it to benign bony pathology requiring no specific treatment but patient did not respond to symptomatic management. FNAC done elsewhere was inconclusive, with no bacteria on Gram's staining and negative bacterial culture and AFB smear examinations. Patient had possible exposure to tuberculosis and Mantoux skin test done which showed significant induration. Possible differential diagnoses related to clavicle including infective, neoplastic, rheumatological, degenerative and idiopathic conditions considered. Magnetic resonance imaging (MRI) showed focal periosteal reaction with marrow signal changes with sparing of sternoclavicular joint. Correlation between patient's history, clinical findings and investigations done and diagnosis of isolated clavicle tuberculosis was made. Patient showed good response to anti tubercular chemotherapy. Repeat MRI showed resolution of initial imaging findings. At the end of 2 years patient was completely symptom free. PMID- 26266176 TI - Risk Factors for Discontinuation of Exclusive Breastfeeding by One Month of Postnatal Age Among High Risk Newborns: An Institution Based Case Control Study. AB - BACKGROUND: Beyond one month of age, there is generally a drop in the proportion of mothers providing exclusive breastfeeding to their infants. Infants with morbidities during neonatal period have been observed to be at higher risk of discontinuation. OBJECTIVE: To enumerate the prevalent factors behind discontinuation of breastfeeding among high risk newborns by first month of life. MATERIALS AND METHODS: A case control study conducted at high risk newborn followup clinic of a teaching medical institute in northern India between January and May 2013. Infants were divided on the basis of continuation (controls) or discontinuation (cases) of exclusive breastfeeding at one month of age. The socio demographic factors along with maternal and neonatal medical factors were compared among groups. RESULTS: During the study period, 112 newborns were screened. Forty seven cases and thirty eight controls were enrolled and finally evaluated. Female gender of newborn, less educated mothers and large families were observed to be associated with discontinuation of exclusive breastfeeding during first month of life among high risk newborns. Requirement of parenteral fluids during hospital stay emerged as the only independent medical reason. CONCLUSION: As in healthy newborns, the socio-cultural factors overshadow the medical reasons for discontinuation of exclusive breastfeeding during first month of life among high risk newborns. PMID- 26266177 TI - Root-Cause Analytical Survey for Measles Outbreak: Vaccination or Vaccine?- A Study From Madhepura District, Bihar, India. AB - INTRODUCTION: Though measles is a vaccine preventable disease, outbreaks still continue to occur because of poor immunization coverage rate at the national level. OBJECTIVE: To report the survey results of an outbreak of measles in Puraini village of Madhepura district in Bihar, India. MATERIALS AND METHODS: This cross-sectional survey was conducted among children aged 6 months to 12 years during an outbreak of measles in December 2008. WHO case definition criteria was used to define active measles cases. Demographic data, immunization status, and disease outcome among the cases was obtained by pre-structured questionnaires. Blood samples from 5 cases were sent for laboratory confirmation. RESULTS: A total of 52 cases and 8 deaths were reported with an attack rate of 28% and case fatality rate of 15.4%. Out of 35% cases of post-measles complications, dysentery with pneumonia was the most common. Anti-measles IgM antibody tested positive in all the 5 serum samples sent for confirmation. No child had received measles vaccination in the past, and the reasons were lack of awareness, lack of faith on vaccination, and unavailability of health workers. CONCLUSION: This survey calls for strengthening of disease surveillance and routine immunization coverage to achieve measles control in these communities. This has important public health implication for the whole country regarding measles elimination in near-future. PMID- 26266178 TI - Clinical Risk Index for Babies (CRIB II) Scoring System in Prediction of Mortality in Premature Babies. AB - BACKGROUND: Clinical Risk Index for Babies scoring system (CRIB II) score is a recently developed tool to predict initial risk of mortality amongst low birth weight babies, the utility of which is scarce in many developing countries. OBJECTIVE: To assess the efficiency of CRIB II score as a tool to predict the risk for neonatal mortality among the LBW babies admitted to neonatal intensive care unit (NICU) at a tertiary care facility Kasr El-Aini paediatric hospital, Cairo, Egypt. MATERIALS AND METHODS: Prospective cohort study design where 113 neonates, admitted during the first 24 hours to the NICU of Kasr El-Aini Hospital, from November 2013 till May 2014 were included. On admission, history taking, neonatal examination, arterial blood gas analysis and variables of CRIB II score were done. Subjects were followed up from admission till discharge or death. RESULTS: Male to female ratio was 1.1:1. Gestational age ranged from 25-32 weeks, the birth weight ranged from 700-1500 gm with mean of 1134.5 (+/- 202). CRIB II score ranged from 1-19 with a mean of 9.9 (+/- 4.0). The total mortality in the included cohort was 34.5% (31/113). Significant positive correlations were found between gestational age, birth weight, temperature, excess base, CRIB II score and the occurrence of mortality and with progressive increase in mortality with increasing CRIB II score (p=0.001). CRIB II score >= 11, gestational age <= 28 and birth weight <= 1100 were all found to be significantly associated with neonatal mortality. Area under ROC curve for CRIB II, gestational age and birth weight were found to be (0.968, 0.900 and 0.834) respectively. CRIB II score with cutoff point of >= 11 was the most sensitive (94.9%) with the predictive value (74.0%) and specificity (82.4%) compared to birth weight and gestational age. CRIB II score showed good calibration to predict neonatal mortality as demonstrated with Hosmer-lemeshow goodness of fit test (p= 0.952). CONCLUSION: CRIB II score is a valid tool of initial risk assessment in LBW, predicting outcome more accurately than birth weight or gestational age alone. It is easily applicable and should replace the traditional models as predictor of neonatal outcome. PMID- 26266179 TI - Normal Bowel Pattern in Children and Dietary and Other Precipitating Factors in Functional Constipation. AB - AIM: To study the bowel pattern of children in general population and children with habit constipation with respect to food habits and regarding psychosocial aspect of toileting. MATERIALS AND METHODS: A prospective descriptive study was done in the Institute of child health and hospital for children, Chennai, with two groups, Functional constipation group and Normal bowel pattern group. The functional group included the children with the age group of 2-12 years, of either sex who fulfilled the ROME III criteria for constipation. Normal bowel pattern group had school children of age group 6-12 years of age and 2-5-year-old children attending OPD for minor ailments. The demographic profile, socioeconomic status, complaints, psychosocial aspects affecting bowel pattern and diet chart were collected and recorded from the parents in proforma. Stool frequency and type of stool passed were recorded for a week, with Bristol stool chart. RESULTS: A total of 523 and 131 children were analysed for normal bowel pattern and functional constipation respectively. Data analysis done using SPSS version 15. The prevalence of functional constipation was noted in 13.5% with female preponderance and in the age group of 2-4 years. CONCLUSION: Constipation continues to be a problem, mostly under recognised in older population. Psychosocial factors had a significant effect on functional constipation. Skipping breakfast, early toilet training, low intake of vegetables and fruits were other factors of significance leading to constipation. PMID- 26266180 TI - Screening for Hearing Impairment in High Risk Neonates: A Hospital Based Study. AB - BACKGROUND: Hearing loss very early in life can have multiple deleterious effects on the new born most commonly being related to attainment of speech and language. Also, it can affect social, emotional and academic achievement of the child.Early identification of hearing impairment has been shown to improve prognosis and hence screening programs have been widely and strongly advocated. AIMS AND OBJECTIVES: To estimate the incidence of neonatal hearing loss in high risk neonates admitted in tertiary level teaching hospital and to determine the risk factors predictive of hearing impairment in them. MATERIALS AND METHODS: It was a prospective study over a period of one year. We screened high risk neonates for hearing impairment admitted to NICU using Brain stem Auditory Evoked Response (BAER).The morphology of the response and wave and interwave latencies was examined in respect to age-appropriate forms. Follow up BAER after one month was performed in cases where initial BAER was abnormal. Babies who tested abnormal on the follow-up were referred for detailed audiology diagnostic work up. RESULTS: A total of 200 cases comprising 118 males (59%) and 82 females (41%) were enrolled. On initial BAER testing, 18 (15.25%) males and 14 (17%) female neonates had hearing loss. Whereas 7 males (70%) and 3 females (30%) had hearing loss out of the total 10 hearing loss cases in the Follow up-BAER testing. Two out of the 6 neonates with birth weight <1500g had hearing loss in the follow up of BAER testing. Use of ototoxic medications, hyperbilirubinemia requiring exchange transfusion, perinatal asphyxia and bacterial meningitis were the major risk factors occurring in 45%, 30% and 26% and 10%. Five neonates had unilateral hearing loss and the rest five (5%) had bilateral impairment.Meningitis was the significant independent clinical risk factors for predicting hearing impairment in high risk neonates.The risk of BAER increased cumulatively with BAER abnormality rate of 4.2%, 22.2% and 33.3% with one two and three risk factors respectively. CONCLUSION: The overall incidence of hearing loss in initial BERA testing was 16%, in males it was 15.25% in males and in 17% in females,only 62.5% of neonates had a persistent abnormal BAER, with male gender a significant risk factor for this. The incidence of hearing loss increased with number of risk factors. The study highlights that although universal hearing screening programs are warranted; most newborns with a detected hearing loss can be identified based on the risk factors. Thus, a targeted approach for hearing screening may be more feasible in resource limited settings. PMID- 26266181 TI - Tuberculosis and Acute Deep Vein Thrombosis in a Paediatric Case. AB - Deep vein thrombosis (DVT) may be associated with tuberculosis infection. DVT in tuberculosis (TB) is implicated to the release of inflammatory cytokines, decrease synthesis of anti-coagulant proteins and increased fibrinogen levels. Drugs may also predispose to the hyper-coaguability. DVT may correlate with the severity of mycobacterium infection. We report a case of DVT in an 11-year-old child with sputum positive pulmonary tuberculosis. The patient was put on low molecular weight heparin after Doppler documentation of thrombosis of left femoral vein. She was then put on oral warfarin with complete resolution of the thrombosis. A clinician should be aware of this rare but dangerous association of tuberculosis and must not delay in early diagnosis and intervention. PMID- 26266182 TI - Sinonasal Neoplasia - Clinicopathological Profile And Importance of Computed Tomography. AB - BACKGROUND: Nasal cavity and Paranasal sinus malignancies are very rare, in which maxillary sinus is the commonest, followed by ethmoid, frontal and sphenoid sinus. Computed Tomography (CT) & Magnetic Resonance Imaging (MRI) play a key role in diagnosis, staging and management of paranasal sinuses and nasal pathologies. Multiplanar imaging in CT helps better imaging of critical anatomical areas. Aim of our study was to study the incidence, clinical features, CT features and its importance in the management of sinonasal neoplasms. MATERIALS AND METHODS: This prospective study was carried out in a tertiary care hospital of MP, India. Consecutive 40 histologically proven cases of sinonasal neoplasia who visited the Department of Otorhinolaryngology and Radiotherapy are included in our study. Demography and clinical features were recorded. Cases of nasal and paranasal sinus masses diagnosed on CT attending ENT and Radiotherapy OPD or admitted in the Radiotherapy ward forms the material of this study. This included patients of both sexes and all ages. Histopathological examination was asked to confirm the diagnosis made on CT. RESULTS: There were total 40 cases of sinonasal neoplasia among which 24 were benign. Almost all the benign cases were seen in the age group <40 y with mean age of 20 y and most of the malignant cases were seen in the age group above 40 y with mean age of 55 y. In our study we found male preponderance with male female ratio of 4:1 in both benign and malignant conditions. The commonest presenting symptoms of the patients with sinonasal masses in our study was nasal obstruction (75%) and nasal discharge (67.5%) followed by nasal mass (65%), epistaxis (62.5%) and headache (60%). Angiofibroma and papilloma were the commonest benign lesions. Commonest malignant lesion was squamous cell carcinoma. Of the malignant Sinonasal tumours studied in our series, maxillary sinus was involved in 13, ethmoid sinuses and nasal cavity in 10 cases each, and frontal sinuses in 2 cases. CONCLUSION: Contrast enhanced computed tomography with multiplanar reconstruction is an excellent modality for imaging sinonasal masses. CT can define the character of the sinonasal mass, thus differentiating benign from malignant. CT helps better imaging of critical anatomical areas and helpful in planning treatment procedures such as surgery and radiotherapy. PMID- 26266183 TI - Is the Mean Platelet Volume in Patients with Acute Cholecystitis an Inflammatory Marker? AB - INTRODUCTION: Acute cholecystitis is an inflammatory disease of the gallbladder. Ultrasonography (US) is the initial and the most valuable method in the diagnosis of acute cholecystitis. Also, laboratory findings are used to support the diagnosis. The aim of the present study was to evaluate the diagnostic value of mean platelet volume (MPV) and platelet (PLT) counts in patients with acute cholecystitis. MATERIALS AND METHODS: From January to August 2014, the medical records of patients were reviewed for the diagnosis of acute cholecystitis. The study included 60 age-matched patients with acute cholecystitis and 60 healthy individuals as a control group. Patients with a chronic disease were excluded from the study. Over all, patients with acute cholecystitis and patients in the control group were evaluated for their MPV, PLT count, platelet distribution width (PDW), platelet crit (PCT) and erythrocyte sedimentation rate (ESR) in a complete blood count (CBC). RESULTS: The MPV values were found to be significantly lower in the acute cholecystitis group when compared to the control group. The PDW and PCT were found to be significantly higher in the acute cholecystitis group when compered to the control group. When a correlation test was performed, MPV was negatively correlated with PLT and PCT counts. CONCLUSION: US is the initial and the most important imaging method for diagnosing and evaluating the biliary system. Also, laboratory findings such as WBC, ESR and CRP support the diagnosis but may have some undesirable limitations. However, MPV is an acute phase reactant that does not require an additional cost because it is already worked in the CBC. Therefore, MPV can be used as a marker in diagnosing inflammatory diseases. PMID- 26266184 TI - Is MRI Necessary for Skeletal Evaluation in Sickle Cell Disease. AB - BACKGROUND: More than 50% of the world's cases of sickle cell anaemia are in India with an estimated population of 1.27 billion as against estimated world's population of 7.24 billion. AIM: MRI of 103 patients of sickle cell disease were evaluated to assess the skeletal changes in proven cases of sickle cell disease and to find the incidence of bony infarcts in such patients. The conversion of red marrow to yellow marrow in these patients were also studied. MATERIALS AND METHODS: Sickle cell patients with musculoskeletal pain as well as asymptomatic sickle cell patients were evaluated by MRI. The standard sequences used wereT1WI, T2WI, STIR, T1WI + Gd Contrast. RESULTS: Persistent Red marrow was seen in axial and appendicular skeleton (62 cases). Extramedullary haematopoiesis was found in 4 cases, avascular necrosis of femur head (32 cases) and bone infarcts (46 cases) were also observed in our study. Osteomyelitis, septic arthritis and tubercular infections were associated with sickle cell disease in our study. CONCLUSION: MRI is very sensitive in detecting early stages of avascular necrosis, red marrow persistence, extramedullary haematopoiesis, changes of arthritis, infections and joint effusion. PMID- 26266185 TI - Diagnostic Utility of Conventional Radiography in Head Injury. AB - BACKGROUND: Head injury is the frequent cause of morbidity and mortality and frequently encountered in emergency department. Radiological examination of the skull is an indispensable part in the management of patients suffering from head trauma. AIM: To determine the accuracy of X-ray in detecting skull fractures, comparing the same with autopsy and CT evaluation. MATERIALS AND METHODS: The medico-legal cases that died of traumatic head injury and brought for autopsy over a period of two years were included in the study. Only those cases were selected who had underwent both X-ray and CT evaluation prior to death. RESULTS: When compared with autopsy, X-ray missed 19.1% of fractures while 11.9% fractures missed in contrast to CT scan. CONCLUSION: Skull X-ray is of little benefit when a CT scan is obtained. It has no added advantage over CT scan. Whenever there is facility of CT scan is available, the patient of head injury should not underwent X-ray as it can only delay the diagnosis of an associated intracranial injury and exposes the already traumatised patient to harmful radiations. PMID- 26266186 TI - Spontaneous Tracheal Rupture in a Case of Interstitial Lung Disease (ILD): A Case Report. AB - Spontaneous tracheal rupture is one of the rare life threatening conditions. Tracheal lacerations are generally secondary to cervical or chest trauma or occurring as a complication of endotracheal intubation. Only two cases of spontaneous tracheal rupture are reported, in adults, one due to acquired tracheobronchomalacia and other due to long term steroid use. We hereby report a very rare case of spontaneous tracheal rupture in young male patient of interstitial lung disease (ILD) who was on steroids for two months and developed spontaneous subcutaneous emphysema and pneumomediastinum. Tracheal rupture was diagnosed on unenhanced computed tomography (CT) and reconstructed virtual bronchoscopic images. Patient subsequently died due to cardiac arrest. PMID- 26266187 TI - Grave Complication of Pharyngitis: Lemierre syndrome. AB - Fusobacterium necrophorum is the causative agent in the pharyngitis. After invasion of the oropharyngeal mucosa by the organism leads to the development of the grave complications like superficial thrombophlebitis of internal jugular vein, septic emboli in the lung and coagulopathy. A 23-year-old male presented with chief complaints of sore throat, headache and high grade fever with past history of upper respiratory tract infection one month ago. On examination, he had high grade fever, tachycardia, hypotension and tender cervical lymph nodes. Oropharyngeal mucosa appeared ooedematous and congested. Leucocytosis with raised ESR was present. Blood culture positive for Fusobacterium necrophorum. Dilated right IJV with the hypoechoic thrombosis seen on Ultrasonography & Doppler. Patient was diagnosed as a case of Lemierre syndrome secondary to oropharyngeal infection was made. He was treated with intravenous imipenem and metronidazole, and then shifted to oral amoxicillin. After completion of full course of the therapy of 6 weeks, patient was improved clinically and all routine blood investigations were normalized. Blood culture was negative for Fusobacterium necrophorum. No evidence of thrombosis within the right internal jugular vein on Doppler. PMID- 26266188 TI - Spontaneous Chest Wall Interstitial Emphysema Secondary to Chronic Empyema Thoracis. AB - Spontaneous extension of air from the pleural space to the chest wall, also referred to as pneumothorax necessitans (PN), is a rare occurrence. Few of such cases have been reported in the literature, some appear to have a pattern of extension from pleural cavity to chest wall. Clinical conditions known to predispose to this complication are pneumothorax, empyema thoracis and tuberculosis of the pleural space or rib. We report a case of PN arising as complication of postpneumonectomy empyema (PPE) secondary to broncho-pleural fistula. Imaging features are highlighted emphasizing the likely pattern of spread. PMID- 26266189 TI - Oral Squamous Cell Carcinoma Metastases to the Kidneys: Is It Common? PMID- 26266190 TI - Fluid Administration Before Caesarean Delivery: Does Type and Timing Matter? AB - BACKGROUND: The effectiveness of fluid preloading is in doubt, so co-loading has been attempted to reduce the incidence of spinal anaesthesia induced hypotension in caesarean patients. AIM: To compare crystalloid preloading, colloid preloading and colloid co-loading for prevention of maternal hypotension in caesarean delivery. SETTINGS AND DESIGN: Study conducted in tertiary level hospital on 90 ASA I/II term parturients posted for elective caesarean section. Patients were randomly allocated to three Groups. MATERIALS AND METHODS: Group A (n=30) was given 10 ml/kg of 6% hydroxyethyl starch (HES) 20 minutes prior to spinal anaesthesia, Group B (n=30) was given 10 ml/kg of 6% HES by rapid infusion in 10 minutes immediately after spinal anaesthesia and Group C (n=30) was given 10 ml/kg of Ringer's Lactate 20 minutes prior to spinal anaesthesia. Intraoperatively, Heart rate, systolic, diastolic and mean arterial pressure were recorded every five minutes. Episodes of hypotension were recorded and treated with bolus of 5 mg of ephedrine and total amount of ephedrine was noted. Adverse effects, if any were recorded. STATISTICAL ANALYSIS: ANNOVA for Quantitative Analysis and chi-Square test and Z-test for Qualitative Analysis. RESULTS: Baseline parameters were similar in all the three Groups. Heart rate decreased from the baseline in all the three Groups, however, mean heart rate was highest in Group C. Heart rate was statistically similar in Groups A and B. MAP decreased in all three Groups from baseline, however, highest fall was recorded in Group C whereas, MAP was statistically similar in Groups A and B. Incidence of hypotension was 66.66% in Group C as compared to 36.66% in Groups A and 40% in Group B respectively. Group C patients received 5.33+/-4.54 mg of ephedrine as compared to 2.00+/-2.82 mg in Group A and 2.33+/-3.14 mg in Group B. Thus, the incidence of hypotension and ephedrine consumption was significantly higher in Group C as compared to Groups A and B whereas, this difference was statistically not significant among Groups A and B. CONCLUSION: Colloid preloading and co loading are equally effective and both are superior to crystalloid preloading for prevention of maternal hypotension in caesarean section patients. PMID- 26266191 TI - The Effect of Whole Body Massage on the Process and Physiological Outcome of Trauma ICU Patients: A Double-Blind Randomized Clinical Trial. AB - BACKGROUND AND AIM: Hospitalization of traumatic patients in the Intensive Care Unit (ICU) and their critical condition can cause haemodynamic instabilities and deterioration in the level of consciousness. The study aimed to investigate the effect of whole body massage on the vital signs, Glasgow Coma Scale (GCS) scores and arterial blood gases (ABG) in trauma ICU patients. MATERIALS AND METHODS: In a randomized, double-blind trial, 108 trauma ICU patients received whole body massage {experimental group (n=54)}, or routine care {control group (n=54)}. The patients vital signs; systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory rate (RR), pulse rate (PR), Temperature (T), GCS score and ABG parameters were measured by a nurse at the same time in both groups before the intervention and 1 hour and 3 hours after the intervention with a checklist. The patient in experimental group received full body massage in 45 minute by a family member. RESULTS: According to the findings, significant differences were observed between experimental and control groups in SBP 1 hour and 3 hours after intervention (p< 0.001), DBP, RR and PR 1 hour after intervention (p<0.001) and GCS 1 hour and 3 hours after intervention (p<0.05). Of ABG parameters, significant differences were observed between experimental and control groups in O2 saturation (p<0.001), PH (p<0.001) and pO2 (p<0.05). No significant differences between experimental and control groups in Temperature, pCO2 and HCO3 (p>0.05). CONCLUSION: With respect to this study, massage therapy is a safe and effective treatment in intensive care units to reduce patient's physical and psychological problems. Therefore the use of massage therapy is recommended to clinical practice as a routine method. PMID- 26266192 TI - The Incidence of Severe Diarrhea with Transdermal Fentanyl Patch: An Uncommon Event. AB - Cancer pain is a major problem for the health care providers. One of the most important aspects of cancer pain is palliative care management. Recently, different research finding shows the efficacy of opioid analgesics such as fentanyl transdermal patch in chronic pain management. Transdermal Fentanyl patches may cause side effects such as drowsiness, dizziness, itching, life threatening or serious breathing difficulties and diarrhea, mainly during the first 72 h of patient's treatment initiation and any time when the drug's dose is increased. We report three case reports of severe diarrhea without most common side effects associated with Fentanyl patches during first 72 h of patient's treatment. PMID- 26266193 TI - Anaesthesia for a "Scalped" Patient. AB - Trichilemmal carcinoma of scalp is a rare malignant tumour of scalp. A 52-year old female presented with an extensive ulcerative lesion of the scalp. As the location of the tumour was in the occipital region and there was loss of bony skull in the region, this case became challenging. This patient was managed in the left lateral which was a difficult situation for even the experienced Anaesthesiologist. Intravenous access was acquired, central venous catheter (CVC) was placed in the right internal jugular vein under ultrasonography (USG) guidance and intubation was carried out in the lateral position. After the procedure, patient was again returned to the left lateral position. The trachea was extubated in the lateral position once the patient was awake, after thorough reversal of neuromuscular blockade. Patient had an uneventful postoperative period. This case report highlights the management of an unusual case of Trichilemmal carcinoma of the scalp. PMID- 26266194 TI - Acute Pulmonary Oedema: A Post-Operative Complication Due to Neostigmine and Post Obstructive Pulmonary Oedema in a Case of Tonsillectomy. AB - Acute pulmonary oedema has been described in relation to perioperative period. The aetiology may be multifactorial and its management poses a challenge to the anaesthesiologist. Its occurrence in a normal healthy person with no other medical history makes the diagnosis difficult. The causes of pulmonary oedema are cardiac failure, fluid overload, airway obstruction, acid aspiration, gas embolism, anaesthetic drugs, sepsis, anaphylactic reaction and reaction to blood & blood products. Early detection, prompt management by an anaesthesiologist will help to prevent further postoperative complications. We report a case of 9-year old male child, posted for tonsillectomy under general anaesthesia, who developed acute pulmonary oedema following extubation after reversal with neostigmine and how we managed it successfully. PMID- 26266195 TI - Assesment of Heart Rate Variability As A Measure of Cardiac Autonomic Status in Psychiatric Patients Exposed to Chemical Irritants. AB - BACKGROUND AND PURPOSE: However, little is known about the cardiac autonomic activity due to chemicals in psychiatric patients. Therefore, the objective of this study was to assess the effect of chemical irritants on the ANS of the person and measure that in the form of Heart Rate Variability (HRV), a noninvasive method to estimate the cardiac autonomic activity. The autonomic nervous system can significantly compromised by use of chemical irritants. MATERIALS AND METHODS: A cross-sectional hospital based study was conducted in which 33 patients (mean age: 29.94 years) of depression/anxiety were compared with 37 age matched controls (mean age: 28.10). The patients who were diagnosed as either depressed or anxious by the psychiatry were included in the study group by random sampling. Out of these 8 patients gave positive history of odour use. Thirty seven age matched healthy persons were taken as controls. Grading of patients was done according to DSMV-IV criteria and short- term HRV was recorded. Five minute HRV recording was done and time domain and frequency domain indices of HRV were assessed using RMS Polyearite D. The result in case and control groups was compared. RESULTS: We have reported a poor HRV compared to control group in patients of depression/anxiety as reflected by NN50 values (p< 0.05). Although not significant the trend shows a better HRV control in almost all the time domain and frequency domain parameters in controls compared to cases. Regarding the history of use of chemical irritants the trend showed a poor HRV control in these cases compared to the patients who did not give any such history. CONCLUSION: Our results suggest that impaired cardiac autonomic nerve function characterized by sympathetic over activity may occur in depression/phobic patients. The study also proves a poor HRV in psychiatric subjects with history of use of odoriferous substances. PMID- 26266196 TI - A Comparative Study of Efficacy and Safety of Agomelatine and Escitalopram in Major Depressive Disorder. AB - BACKGROUND: Major depressive disorder (MDD) is a mental disorder characterized by episodes of depressed mood, loss of interest or pleasure, feeling of guilt or low self-esteem, loss of energy, altered sleep patterns and difficulty in concentration. OBJECTIVE: This study was carried out to compare the efficacy and safety of Agomelatine with Escitalopram in the treatment of major depressive disorder. DESIGN AND SETTING: This is a prospective study conducted at Outpatient Department of Psychiatry, GSL Medical College & General hospital, Rajahmundry, India. MATERIALS AND METHODS: Patients with newly diagnosed major depressive disorder (DSM-IV-TR) with minimum score of 20 in Hamilton depression rating scale were randomly assigned Agomelatine (25-50 mg/day) or Escitalopram (10-20 mg/day) for a period of 8 weeks. The main efficacy outcome considered was the mean change of HAM-D17 score from baseline to end of therapy. Secondary outcome measures were Clinical Global Impressions-improvement (CGI) and severity (CGI-S) rating scales. STATISTICAL ANALYSIS: Student t-test was used for comparing the groups and chi square test was used for assessing the qualitative variables. For all statistical analysis p<0.05 was considered statistically significant. RESULTS: The drugs under study effectively reduced depressive symptoms at all the time points. The percentage of responders at 8weeks (last post baseline value) was 65.38% with Agomelatine and 57.40% with Escitalopram. The difference between the drugs was statistically not significant in all evaluations (p>0.05). The mean CGI-S and CGI I scores were decreased in both the groups (p<0.05) and there was no statistically significant difference between the groups at any assessment during the study period. Both the treatment groups showed favourable safety profile. CONCLUSION: The study results supported that Agomelatine is therapeutically similar to Escitalopram in terms of antidepressant effect. PMID- 26266197 TI - Sociodemographic Pattern of Depression in Urban Settlement of Karachi, Pakistan. AB - INTRODUCTION: Depression is a global issue prevalent among developing countries like Pakistan as compared to developed countries. We conducted a study to assess the prevalence and identify the significant predictors of depression in an elite urban settlement in Karachi, Pakistan. MATERIALS AND METHODS: This cross sectional study was done in the elitist residential area of Karachi; Defence Housing Authority (DHA). Four hundred and twenty three participants were included by going to their residences. Self-administered questionnaires were handed out after taking informed consent. Level of depression was assessed by Patient Health Questionnaire (PHQ-9). Data were entered and analysed in Predictive Analytical Software v. 18.0. RESULTS: The mean and median total score of the scale were 5.9 +/- 5.4 and 4 (7) respectively with minimum score 0 and maximum 27. In this sequence, 139 (32.86%) respondents were identified to be depressed. It was found that females were slight more depressed than males (p = 0.063). Regression Model identified only gender and marital status as significant predictors of depression. Having a female gender increased 0.658 times chance of being depressed (p = 0.047). Unmarried person had 0.296 times more likely to be depressed (p = 0.019). Boredom was considered as significant factor of depression by the participants (p< 0.0001). Odds ratio signified depression occurred 0.310 times more if one was bored. DISCUSSION: Depression should be considered as a major public health issue for the city. Public awareness should be done in all parts of the city in an attempt to reduce depression especially among the female gender. PMID- 26266198 TI - Acute Psychosis after Recent Isoniazid Initiation. AB - Isoniazid as part of Directly Observed Treatment-Short course (DOTS) regimen is universally used. Although, associated psychosis in certain cases is documented earlier, type of symptoms and onset of symptoms remains highly variable. We describe a case of 54-year-old female on anti-tubercular therapy with onset of psychosis within three days of Isoniazid initiation characterised by agitation, loosening of association, echolalia with spontaneous remission after drug stoppage. This case highlights the importance of remaining vigilant and considering isoniazid as possible causative agent for psychosis even within days of its intiation and avoiding delay in management. PMID- 26266199 TI - Use of 90 degrees Hopkin's Telescopic Examination as an OPD Tool to Clinically Evaluate and Record Oral Cavity Lesions: Our Experience in Early Detection, Especially in Patients with Limited Mouth Opening. AB - INTRODUCTION: Restricted mouth opening due to premalignant lesions like oral sub mucous fibrosis, malignancies of oral cavity and postoperative status is very common in Indian patients. It is very difficult to evaluate, document and biopsy the lesions due to inability to access, vast area and diversity of premalignant lesions and subject variations. 90 degrees Hopkin's slender out-patient examination telescope was found useful tool in this. AIM: The aim of the study was to evaluate the use of magnified view and reach of a slender telescope to document and examine the oral cavity for any premalignant and malignant lesions, especially for patients with restricted mouth opening and to study its impact on management. MATERIALS AND METHODS: A 90(0) Hopkin's telescope was used to evaluate and document oral cavity examination in the Out Patients Department (OPD). The data of first 2000 patients was analysed. RESULTS: Difficult to reach areas, where mouth opening was severely restricted was the significant subset. A total of 1394 patients approached OPD for primary diagnosis at our tertiary cancer care centre. Six hundred and six patients were the ones in follow up after treatment in form of Surgery, Chemotherapy or Radiotherapy, or combination. Five twenty three patients (of 1394) with mouth opening <= 20mm formed the study group. Telescope guided biopsies were also taken in 50 patients from 56 sites. Serial recordings were compared objectively in premalignant, treatment evaluation and close watch groups. An increase of 5.6% in rate of diagnosis of malignancy was made possible with the help of telescopic examination in patients with mouth opening <= 20mm. CONCLUSION: A 90(0) Hopkin's telescopic examination is a useful tool to evaluate and record oral cavity lesions, especially in patients with restricted mouth openings. It is a useful tool for screening high risk group, giving definite advantage of objective evaluation and recording of the lesion. It can also be used to objectively evaluate response of neo-adjuvant chemotherapy and as a teaching tool for the fellows. PMID- 26266200 TI - Radiobiological Response of Cervical Cancer Cell Line in Low Dose Region: Evidence of Low Dose Hypersensitivity (HRS) and Induced Radioresistance (IRR). AB - BACKGROUND: Purpose of the present study was to examine the response of cervical cancer cell line (HeLa cell line) to low dose radiation using clonogenic assay and mathematical modeling of the low dose response by Joiner's induced repair model. MATERIALS AND METHODS: Survival of HeLa cells following exposure to single and fractionated low doses of gamma (gamma)-ray, 6 MV, and 15 MV photon was measured by clonogenic assay. RESULTS: HeLa cell line demonstrated marked low dose response consisting of an area of HRS and IRR in the dose region of <1 Gy. The two gradients of the low dose region (alphas and alphar) were distinctly different with a transition dose (Dc) of 0.28-0.40 cGy. CONCLUSION: HeLa cell line demonstrates marked HRS and IRR with distinct transition dose. This may form the biological basis of the clinical study to investigate the chemo potentiating effect of low dose radiation in cervical cancer. PMID- 26266201 TI - Preliminary Experience and Morbidity Analysis of Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC) from a Tertiary Cancer Center in India. AB - BACKGROUND: Peritoneal carcinomatosis (PC) can arise directly from peritoneum (primary) or from regional spread of gastrointestinal and gynecological malignancies. It is often considered a terminal event. CRS/HIPEC procedure provides encouraging outcomes in select sub-set of patients with PC. In this study we present our initial experience of this combined procedure from a tertiary cancer care center in India. MATERIALS AND METHODS: Between January 2014 to January 2015, 13 patients underwent CRS + HIPEC procedure at our center. Preoperative assessment for cytoreduction was done using contrast CT-scan of the abdomen and staging laparoscopy. All procedures were performed by the same surgical team. After cytoreduction, HIPEC was performed by closed method. RESULTS: Median patient age was 52 and median PCI was 13.5 (5-21). Ovarian cancers were commonest origin of PC in our series. All patients had a complete cytoreduction with a median operative time of 8.3 hours. Postoperative ileus was the commonest adverse event. In the immediate postoperative period, major complications were observed in 23% (3/13) of our patients (1. intra-abdominal abscess 2. Septicemia and liver function derangement 3. Bowel obstruction which required a re-operation. Median hospital stay was 12 days (range 9-45 days) and there was no perioperative mortality. CONCLUSION: Our initial results indicate that CRS + HIPEC procedure can be performed with acceptable morbidity and no mortality. Appropriate case selection by a multi-disciplinary team is vital to achieve complete cytoreduction and optimize outcomes. PMID- 26266202 TI - Pre-radiotherapy Haemoglobin Level is A Prognosticator in Locally Advanced Head and Neck Cancers Treated with Concurrent Chemoradiation. AB - INTRODUCTION: Radiation plays a major role in treatment of locoregional control of Head and Neck Squamous cell carcinoma (HNSCC). Anaemia is considered a contributor to intra-tumour hypoxia and tumour resistance to ionizing radiation and most evidences are from developed world, we prospectively investigated the exact role of anaemia in treatment outcome of Stage III/IVA HNSCC in our patient population. AIM OF THE STUDY: Primary end point: To analyse the Pre-Radiotherapy haemoglobin level and early response of treatment in stage III/IVA HNSCC and to determine the relationship of Pre-Radiotherapy haemoglobin level with other prognostic factors. MATERIALS AND METHODS: This non-interventional single blinded randomized study enrolled patients attending the OPD consecutively, who met our eligibility criteria. INCLUSION CRITERIA: HNSCC patients of Stage III/IVA aged >=18 years and <= 70 years with ECOG status of 1or 2 and willing for concurrent chemoradiation and at least 6 weeks of follow up. EXCLUSION CRITERIA: 1) Previous history of treatment for malignancy or radiation in head and neck site. 2) Patients with other fatal and non-fatal pre-morbid or co-morbid conditions that can affect the outcome or the overall survival. Patients with Pre-radiotherapy haemoglobin status < 10 g/dl were given haematinic support and/or blood transfusion. All patients received concurrent chemotherapy (weekly cisplatin) and radiation in conventionally fractionated dose of 66Gy. Early treatment responses were evaluated with Revised RECIST version 1.1 and Data analysis using SPSS version 17.0. RESULTS: Ninety one patients enrolled had mean age of 55.63 (range: 32-69), a median of 56 and mode of 60. Seventy one were males (78%) and 20 females (22%) with a performance status of ECOG 1 in 43 (47%) patients and ECOG 2 in 48 (53%); Pre-RT Hb level of <10.7 g/dl in 38 (42%) patients and >=10.7 in 53 (58%) patients; Pre-RT Hb level was <12 g/dl in 67 (74%) patients and >=12 in 24 (26%) patients. Tumour sites were - Nasopharynx 7 (8 %), Oral Cavity 18 (20 %), Oropharynx 32 (35 %), Hypopharynx 23 (25 %) and Larynx 11 (12 %). Twenty five (27%) had Grade 2 mucositis and 66 (73%) had Grade 3 mucositis. Fifty eight (64%) patients completed treatment with NO breaks and 33 (36%) with treatment breaks for >=5 days. Pre-radiotherapy haemoglobin >= 10.7 g/dl (p < 0.001), ECOG performance status (p = 0.0002), Treatment interruptions for > 5 days (p = <0.0001), Mucositis reaction (p = <0.0001) showed statistical significance with outcome of response. CONCLUSION: The study found that performance status, pre-RT haemoglobin level, radiotherapy interruptions > 5 days and non-development of grade III mucositis was found to be significantly associated with good loco regional control. Haemoglobin level >=10.7 g/dl was associated with better treatment outcome, higher performance status, fewer treatment interruptions and lesser degree of mucositis. Transfusion did not affect the outcome. Definitive conclusions and recommendations need further expansion of our study for better statistical power. PMID- 26266203 TI - An Atypical Case of POEMS Syndrome with an Osteolytic Bone Lesion. AB - POEMS syndrome is a rare multisystem disorder with an underlying plasma cell dyscrasia associated with Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin changes. Usually it is associated with sclerotic bone lesions. It usually manifests in 5(th)-6(th) decade of life with a mean survival period of eight years. We report an unusual case of a 28-year-old male diagnosed with POEMS syndrome and had a lytic bone lesion the in sternum. PMID- 26266204 TI - Tumour Angiogenesis and Angiogenic Inhibitors: A Review. AB - Angiogenesis is a complex process depending on the coordination of many regulators and there by activating angiogenic switch. Recent advances in understanding of angiogenic mechanism have lead to the development of several anti-angiogenic and anti-metastatic agents that use the strategy of regulation of angiogenic switch. Antiangiogenic therapy is a form of treatment not cure for cancer and represents a highly effective strategy for destroying tumour because vascular supply is the fundamental requirement for growth of tumour. Because of the quiescent nature of normal adult vasculature, angiogenic inhibitors are expected to confer a degree of specificity when compared to nonspecific modalities of chemo and radiotherapy, so it has the advantage of less toxicities, does not induce drug resistance and deliver a relatively non toxic, long term treatment of tumour. PMID- 26266205 TI - Evaluation of Musculoskeletal Disorders in Dentists and Application of DMAIC Technique to Improve the Ergonomics at Dental Clinics and Meta-Analysis of Literature. AB - INTRODUCTION: Musculoskeletal disorders (MSD) result in discomfort, pain and illness that can result in disruption or impairment of dental practice. MATERIALS AND METHODS: A cross-sectional study consisting of 60 dentists was carried out to determine musculoskeletal work related pain in major cities of Northern India. The study was planned in two phases. In the first phase, the subjects were given questionnaire related to the musculoskeletal pain happened over the last twelve months. In the second phase of study, improvement was carried out by recommending the subjects to implement ergonomics at their workplace. After three months subjects were again approached and given questionnaire about the musculoskeletal disorders. DMAIC (define, measure, analyse, improve and control) methodology of six sigma strategy was used to access the MSDs. Chi-square test was used for the analysis and a p-value of less than or equal to 0.05 was considered statistically significant. RESULTS: The overall prevalence of musculoskeletal problems in the present study was found to be 68.3%. After three months only 23 respondents applied ergonomics at their work place, prevalence of pain was reduced in neck from 47.8% to 21.7% out of total 23 respondents, shoulder pain 39.1% to 17.3%, pain in elbows from 26% to 21.7%, as well as in other locomotor organs. The p value was significant with p <0.05. CONCLUSION: MSD represents a major occupational health issue for dentists in India as well as worldwide and result revealed necessitates the need of workshops to create awareness of ergonomics as effective measures for reducing MSD among dentists. PMID- 26266206 TI - A Comparative Analysis of Antimicrobial Property of Wine and Ozone with Calcium Hydroxide and Chlorhexidine. AB - BACKGROUND: The antibacterial properties of wine and ozone have been established but their antibacterial efficacies against endodontic pathogens are yet to be ascertained. AIM: The purpose of this study is to comparatively evaluate the antibacterial property of ozonated water, white wine (14%) and de-alcoholised white wine. MATERIALS AND METHODS: S.mutans and E.faecalis were subcultured and inoculated in a nutrient broth for 24 hours. The following groups were formulated: Group 1A:2% Chlorhexidine (Control group); Group 1B:White wine; Group 1C:Dealcoholised white wine; Group 1D:Ozonated water; Group 2A: Ca(OH)2 + Chlorhexidine (Control group); Group 2B: White wine + Ca(OH)2; Group 2C:De alcoholised White wine + Ca(OH)2 + chlorhexidine; Group 2D:White wine + Ca(OH)2 + chlorhexidine and group 2E: Dealcoholised white wine + Ca(OH)2 + chlorhexidine. The samples were allowed to diffuse into the culture medium for two hours, later the S. mutans were streaked on to the blood agar medium and the E. faecalis were streaked on to the Muller Hilton agar medium and incubated for 48 hours at 370C the zone of inhibition was measured after 48 hours. RESULTS: There was no growth of microorganisms seen with ozonated water. Chlorhexidine showed large zone of inhibition compared to the other groups. White wine has better antimicrobial property than de-alcoholised white wine, but when mixed with calcium hydroxide the dealcoholised white wine has better action against the microorganisms. CONCLUSION: Ozonated water has the best antibacterial property and the antibacterial action of Calcium hydroxide is enhanced when it is mixed with de alcoholised white wine. PMID- 26266207 TI - Is Oral Health of the Sugar Mill Workers Being Compromised? AB - INTRODUCTION: Occupational environment has an immense influence on the general as well as oral health. The specific exposure to sugar and its byproducts might influence the dental health of sugar mill workers. AIM AND OBJECTIVES: The present study was conducted to assess and compare the oral health status of production line workers and administration staff working in the sugar mills of Western Uttar Pradesh. MATERIALS AND METHODS: A cross-sectional study was conducted in four Government aided and four Private sugar mills of West Uttar Pradesh, India among the production line workers and administration staff. Multistage random sampling methodology was employed to select total of 600 sugar mill factory workers (449 production line workers and 151 administration staff). The oral health status of the study subjects was assessed using the modified WHO Oral health survey Performa 1997. STATISTICAL ANALYSIS: SPSS 19 Version was used for statistical analysis. Mean, Standard Deviation and proportions were calculated for each clinical parameter. Student t-test and Chi-square analysis was done to analyse inter group comparison. RESULTS: Mean DMFT for production and non production line workers was 7.67+/- 2.99 and 0.15 +/- 1.34 (p= 0.001) respectively. 80.17% of production line workers had maximum CPI score 2 in contrast to 63.57% of administration staff (p=0.324). CONCLUSION: The dental health was found to be debilitated among the production line workers of Sugar mill as compared to the Administrative staff. It is therefore recommended to raise the awareness among the sugar mill workers regarding the same. PMID- 26266208 TI - Evaluation of Fluoride Retention Due to Most Commonly Consumed Estuarine Fishes Among Fish Consuming Population of Andhra Pradesh as a Contributing Factor to Dental Fluorosis: A Cross-Sectional Study. AB - BACKGROUND: Fluoride in drinking water is known for both beneficial and detrimental effects on health. The principal sources of fluoride include water, some species of vegetation, certain edible marine animals, dust and industrial processes. The purpose of this study was to evaluate the fluoride retention of most commonly consumed estuarine fishes among fish consuming population of Andhra Pradesh. MATERIALS AND METHODS: A cross-sectional study was conducted to evaluate the amount of fluoride retention due to ten most commonly consumed estuarine fishes as a contributing factor to Fluorosis by SPADNS Spectrophotometric method. The presence and severity of dental fluorosis among fish consuming population was recorded using Community Fluorosis Index. Statistical analysis was done using MedCalc v12.2.1.0 software. RESULTS: For Sea water fishes, the fluoride levels in bone were maximum in Indian Sardine (4.22 ppm). Amongst the river water fishes, the fluoride levels in bone were maximum in Catla (1.51 ppm). Also, the mean total fluoride concentrations of all the river fishes in skin, muscle and bone were less (0.86 ppm) as compared to the sea water fishes (2.59 ppm). It was unveiled that sea fishes accumulate relatively large amounts of Fluoride as compared to the river water fishes. The mean Community Fluorosis Index was found to be 1.06 amongst a sampled fish consuming population. Evaluation by Community Index for Dental fluorosis (CFI) suggested that fluorosis is of medium public health importance. CONCLUSION: It was analysed that bone tends to accumulate more amount of fluoride followed by muscle and skin which might be due to the increased permeability and chemical trapping of fluoride inside the tissues. The amount of fluoride present in the fishes is directly related to the severity of fluorosis amongst fish consuming population, suggesting fishes as a contributing factor to fluorosis depending upon the dietary consumption. PMID- 26266209 TI - Impact of Untreated Traumatic Injuries to Anterior Teeth on the Oral Health Related Quality of Life As Assessed By Video Based Smiling Patterns in Children. AB - INTRODUCTION: The aim of the study was to assess the correlation between the oral health status, oral health related quality of life and the evaluations of their smiles as assessed by the children, their parents, and through measurements of the children's videotaped smiles and compare the smiling patterns in children suffering from untreated traumatic injuries to anterior teeth and control group. MATERIALS AND METHODS: Fifty eight children of the age 5-15 years of both sexes were selected for the study and categorized into experimental group and control group. The experimental group consisted of 29 children with untreated trauma to one or more anterior teeth while the control group consisted of 29 children with good oral health. Oral examination of all children was done to include in study groups. Children and parents participating in the study responded to two separate Oral Health Related Quality of Life questionnaires for children and parents respectively. The children were asked to watch a funny cartoon show and a video was made while the children watched the show. The video was cropped into still images at 25 predetermined points. Width and openness of the children's mouth and number of teeth shown were measured during the taped sessions to assess the children's video-based smiling patterns. RESULTS: The children's self evaluation scores had statistically significant correlation with their smiling patterns, the number of traumatized teeth and the parental assessment of their children's oral health. Children with trauma to anterior teeth had more impacts on their smiling pattern compared to control group. CONCLUSION: Children suffering from trauma to anterior teeth had more effects on the emotions, the self confidence and social interaction than children without any traumatic injury. PMID- 26266210 TI - Orthodontic Treatment Provided by General Dentists with Different Types of Appliances in Chattishgarh, India. AB - OBJECTIVE: The study was done to determine the quantity of orthodontics and the type of appliance used for orthodontic treatment by general dentist. MATERIALS AND METHODS: A total of 410 dentists completely participated in the study. The study included questions to know the positive effects of orthodontic treatment done by general dentists and their opinions and qualities regarding the provision of treatment. STATISTICAL ANALYSIS: Statistical analysis was done using SPSS version of 16.0 was used at p <= 0.05. RESULTS: One forty six (35.6%) dentists answered that they practice orthodontic treatment to their patients, of which most were providing removable appliances (39.5%). There was a significant difference between the groups toward the benefits of orthodontic treatment according to experience of service and locality. General dentist were providing this treatment mainly in the mixed dentition period i.e. 96(65.8%). Most of the participants gave positive response regarding expansion of their syllabus related to orthodontics. CONCLUSION: A significant difference in response to the benefits of the treatment were seen according to experience and are of practice and most of the participants showed positive response increasing their courses in orthodontics at undergraduate level. PMID- 26266211 TI - Assessment of Periodontal Status of Konda Reddy Tribe in Bhadrachalam, Khammam District, India. AB - BACKGROUND: Though great strides have been taken globally in the fight against oral diseases, problems persist especially among poor, disadvantaged and socially marginalised communities like tribes. Konda Reddies are one of the most primitive tribes of Bhadrachalam who because of their isolation, inaccessibility to dental resources and lack of dental knowledge follow traditional methods of oral hygiene practices, which are found to be inadequate to maintain oral health. AIM AND OBJECTIVES: To assess the periodontal status of Konda reddy tribes residing in Bhadrachalam of Khammam district, India. MATERIALS AND METHODS: Based on availability and accessibility the tribes were gathered using convenient sampling method. The total study population consisted of 500 subjects. Using a preformed Performa the oral hygiene practices and periodontal status was recorded using CPI index. RESULTS: The total study population was 500, comprising of 225 males and 275 females in the age group ranging from 20- >70 years. The mean number of sextants with healthy condition were 0.04+/-0.19; calculus 4.69+/-1.21; pockets 4 5 mm 0.91+/-0.91 and pockets >6mm 0.02+/-0.15. CONCLUSION: Poor oral hygiene and periodontal status was seen among the tribes. Under these circumstances, the implementation of a basic oral health care programme for these tribes is a high priority. PMID- 26266212 TI - A Unique Bonding Technique for Immediate Orthognathic Surgery. AB - INTRODUCTION: A challenge in orthodontics is achieving ideal bracket position which determines treatment results and finishing. A new bonding method is done indirectly on the cast and bonded directly on the teeth, but it does not require conventional trays to carry the brackets to the teeth. MATERIALS AND METHODS: Heavy sized archwires like 0.019"x0.025" or 0.018" SS are bent to the malocclusion to generate a template which comprises of an Bracket -Archwire Assembly (BAA). This assembly is transferred onto the teeth using the molar bands with tubes which serves as a jig for proper orientation of the BAA, then the adhesive is cured at one shot to complete the bonding procedure. RESULTS: Two surgical cases successfully bonded with this technique is presented in this article. CONCLUSION: This bonding method finds specific advantages in surgical orthodontics - when the surgeon decides on a surgery-first treatment objective, management of single or a couple of periodontally extruded teeth, management of impacted teeth and in patients needing fixed functional appliance immediately before the completion of growth spurt. PMID- 26266213 TI - A Comparison of Masticatory Performance and Efficiency of Complete Dentures Made with High Impact and Flexible Resins: A Pilot Study. AB - BACKGROUND: In patients with extensive tooth loss, restoration of masticatory function and aesthetics is main concern for a prosthodontist. AIM OF STUDY: This study aimed to evaluate and compare differences in masticatory efficiency of patients treated with complete dentures made with either high impact or flexible resins. SETTING AND DESIGN: The sample size consisted of 10 study subjects. Two sets of dentures first conventional followed by flexible dentures were fabricated for each subject and both the sets of dentures were accessed for masticatory performance and efficiency. MATERIALS AND METHODS: This study compared the masticatory performance and efficiency of dentures by means of standardized mesh sieves. Masticatory efficiency was calculated by recording the total number of chewing cycles and time required to completely swallow a standardized food item. A patient satisfaction questionnaire was given and evaluated. STATISTICAL ANALYSIS USED: The statistical analyses were performed using Z-test of Proportion and Paired t-test. RESULTS: The masticatory performance ratio was found to be more for hard food in conventional dentures. The values of masticatory performance ratios for soft food, time and number of masticatory strokes were indicating better masticatory efficiency of conventional dentures. CONCLUSION: Though masticatory efficiency and performance were found to be better for patient's dentures made with Polymethyl methacrylate (PMMA), a statistically significant number of patients reported that the flexible dentures were more satisfying than the conventional dentures. PMID- 26266214 TI - Influence of Vitamin D & Calcium Supplementation in the Management of Periodontitis. AB - INTRODUCTION: It has long been recognized that vitamin D is a hormone and were many studies reporting that patients in periodontal maintenance programs taking vitamin D and calcium supplementation had a trend for better periodontal health compared to patients not taking supplementation. AIM: To evaluate the effect of vitamin D and calcium supplementation in reducing gingival inflammation, using clinical parameters like gingival index (GI), oral hygiene index-simplified (OHIS), probing pocket depth (PPD), clinical attachment level (CAL) and bone density (BD). Also, to assess whether calcium and vitamin D oral supplementation influences alveolar Bone Density (BD). DESIGN AND SETTINGS: A nonrandomised clinical trial done in Amrita School of dentistry, Kochi, India. MATERIALS AND METHODS: Group A taking vitamin D (250IU/day) and calcium (500 mg/day) supplementation, and Group B were not taking oral supplementation. All subjects had at least one or more teeth with chronic moderate periodontitis. Digital Orthopantomogram images were taken to assess bone density. Data were collected at baseline and three months. STATISTICAL ANALYSIS USED: OHI-S, GI, PPD, CAL, and Bone Densities (BD) were calculated per group. Karl Pearson Coefficient of correlation was used to test correlation of bone density with GI and OHI -S. Intergroup comparison of parameters were done using Independent two Sample t test. Intragroup comparison of parameters at recall interval was done using Paired sample t-test. The results were considered statistically significant when p-value was <0.05. RESULTS: Both Groups showed significant change in the periodontal parameters and bone density after three months and intragroup comparison showed highly significant results for vitamin D group in relation to GI, OHI S and bone density. CONCLUSION: Calcium and vitamin D supplementation has got a positive effect on periodontal health and it can be used as an adjunct to non surgical periodontal therapy. PMID- 26266215 TI - Proliferating Cell Nuclear Antigen in Premalignancy and Oral Squamous Cell Carcinoma. AB - INTRODUCTION: Cancer has multifactorial aetiology and is a multistep process involving initiation, promotion and tumour progression. Cellular proliferation is one of the important indicators for the biologic aggressiveness of a malignant lesion. The dysregulated proliferation may be a significant change to determine the potential prognosis of various malignant tumours. AIM: The aim of this study was to evaluate the expression of proliferating cell nuclear antigen (PCNA) as an indicator for clinical aggressiveness in oral premalignancy and squamous cell carcinoma. MATERIALS AND METHODS: A total of 50 blocks were taken from the Department of Oral Pathology which was diagnosed previously histopathologically. It comprised of normal oral mucosa (10), dysplasia (10) and grades of oral squamous cell carcinoma (30) of patients between the age group of 40-60 years. From each block, sections of 4 micro metre thicknesses were prepared and placed on poly- L lysine coated slides. These sections were immunohistochemically stained with monoclonal proliferating cell antibody (PC10). The stained slides were evaluated by a single examiner for cell count. RESULTS: A comparison between study groups and controls showed a probability value (p-value) < 0.05. Significant increase in the proliferative index from the normal to oral squamous cell carcinoma was noticed. Poorly differentiated squamous cell carcinoma showed maximum proliferative index followed by moderately differentiated, well differentiated squamous cell carcinoma, dysplasia and normal mucosa. CONCLUSION: Present study concluded that PCNA index can be used to assess the proliferation and aggressiveness in dysplasia and different grades oral squamous cell carcinoma. PMID- 26266216 TI - Maternal Dental Anxiety and its Effect on Caries Experience Among Children in Udaipur, India. AB - CONTEXT: Dental caries is a common oral disease among children. There are various factors that influence caries development. Parents and family environment influence oral health behaviours among children. Dental Anxiety is a common hindrance in seeking dental treatment. Mothers' dental anxiety may act as a barrier to seek professional advice about their children's caries experience. AIM: To evaluate dental anxiety among mothers and its possible relationship with caries experience in their children in Udaipur city, India. SETTING AND DESIGN: The sample was selected from those attending Darshan Dental College and Hospital, Udaipur for dental treatment. The study period was from June 2014 to November 2014. MATERIALS AND METHODS: A cross-sectional survey was designed. A total of 187 mother-child pairs were recruited for the study. The children's age ranged from 3-14 years. Modified Dental Anxiety Scale (MDAS), Hindi version, was used to evaluate dental anxiety among the mothers that categorizes the dental anxiety into five levels. Demographic detail such as age, educational level, and family income was also collected. The World Health Organization (WHO) criteria was utilized for the diagnosis of dental caries in children. DMFT (Decayed, missing and filled teeth) and DMFS (Decayed, missing and filled surfaces) scores were then calculated. STATISTICAL ANALYSIS: Statistical Package for Social Sciences (SPSS) version 20.0 was used to interpret data. Maternal anxiety scores taken as mean MDAS were compared with various independent variables. Statistical tests were used to compare maternal anxiety and children's caries experience. A p value equal or less than 0.05 was considered as statistically significant. RESULTS: Almost half (49.7%) of the mothers reported as being 'fairly anxious' or 'very anxious'. There was a significant (p=.001) difference in maternal dental anxiety level in relation to age of the children. Mothers of younger children reported higher anxiety scores. Similarly, mothers with lesser education and lesser family income reported higher anxiety scores. The mean decayed score in children of very anxious mothers and phobic mothers was significantly (p=.001) higher as compared to the children of the mothers with lower anxiety levels. CONCLUSION: There was a strong positive association between maternal dental anxiety and children's dental caries experience. PMID- 26266217 TI - A Study to Assess and Correlate Osteoporosis and Periodontitis in Selected Population of Maharashtra. AB - BACKGROUND: Osteoporosis is a systemic bone disorder characterized by decreased bone mass and increased risk for fracture. It has been proposed as a possible risk factor for periodontal disease progression. Recent literature has shown periodontitis to be a risk indicator for osteoporosis, suggesting a possible two way relationship. However the association between these two diseases still remains unclear leading to a scope of further research in this area. AIM: The aim of the present study was to assess and Correlate the severity of osteoporosis and periodontitis by using variables like probing pocket depth, clinical attachment loss, plaque index, body mass index and bone mineral density. MATERIALS AND METHODS: A total of 65 subjects aged between 45-75 years suffering from periodontitis were considered. All subjects were assessed for periodontal disease severity by plaque index (PI), probing pocket depth (PPD) and clinical attachment loss (CAL). The bone mineral density (BMD) of patients was assessed using dual energy X- ray absorptiometry (DXA) at lumbar spine (L1 - L4). The severity of periodontal disease was correlated with severity of osteoporosis. Descriptive statistics like frequency and percentage were calculated for all the variables. Chi-square test was performed to assess the association between the study variables. RESULT: Among the entire group 78.46% had high plaque index score, and the severity of periodontitis increased with increase in plaque index score showing a statistical significance. Osteopenia was observed in 25.33% of the subjects, out of whom 63.15% suffered from severe periodontitis. Osteoporosis was observed in 17.33% of the subjects, and all the subjects (100%) suffered from severe periodontitis. CONCLUSION: The results of the present study suggest that increasing severity of periodontitis increased the risk of osteoporosis and vice versa. We conclude that there is a definite association between periodontitis and osteoporosis. PMID- 26266218 TI - Enhancing the Dental Professional's Responsiveness Towards Domestic Violence; A Cross-Sectional Study. AB - BACKGROUND: Dentists may be the first health care professionals to treat patients who have experienced Oro-facial trauma resulting from Domestic violence (DV). Hence, as a national health concern, it challenges the social responsibility of a dentist in bringing down its prevalence. OBJECTIVE: To assess the knowledge of Domestic violence among dentists of Karnataka. MATERIALS AND METHODS: A cross sectional questionnaire survey was conducted among dentists of Karnataka to know their knowledge, its relation to dentistry and measures they practice to bring down the prevalence of DV victims. RESULTS: Overall knowledge about DV was very less among the dentists & out of 64% who said the dentist has a role in bringing down the prevalence, 28% reported the need for training. CONCLUSION: Based on analysis of the data, dentists were interested and would benefit from additional education opportunities concerning recognizing, referring and managing patients who may be the victim of domestic violence in order to enhance their role. PMID- 26266219 TI - Comparison of the Effect of Dentin Bonding, Dentin Sealing Agents on the Microleakage of Provisional Crowns Fabricated with Direct and Indirect Technique An Invitro Study. AB - BACKGROUND: Postoperative sensitivity after temporization is a common complaint in Fixed Partial Denture patients. It is caused by weak and ill fitting temporary restorations which results in microleakage. This can be controlled by providing good temporary restorations and by coating the exposed dentinal tubules of the prepared tooth with dentin bonding agent or dental varnish. AIM: The purpose of the study was to determine the effect of dentin-bonding, dentin sealing agents on the microleakage of temporary crowns made by tooth colored auto polymerizing resin fabricated with direct and indirect technique. MATERIALS AND METHODS: Thirty premolar and molar human teeth were collected which were extracted recently was used for the study. The teeth were marked and divided into 3 groups each containing 10 nos. They were individually mounted with self-cure acrylic resin. It was then mounted on a milling machine and crown preparations done. Temporary crowns were fabricated by direct and indirect method with two types of materials. In group A (Control group), the temporary crowns fabricated with both direct and indirect method were cemented directly with temporary luting cement. In group B dentine-bonding agent (solobond M) was applied once to the prepared surface of each tooth specimen before the cementation of temporary crowns where as in case of group C a single layer of dental varnish is applied prior to crown cementation. The entire specimens were immersed in 1% methylene blue and allowed to undergo thermal treatment. It was then sectioned in a hard tissue microtome. Each section was evaluated for dye penetration into the dentin tubules by comparing it with a visual scale. STATISTICAL ANALYSIS: SPSS Version 13 software was used for non-parametric data analysis by a qualified statistician. P-values less than 0.05 (p-value<0.05) were considered to be statistically significant. RESULTS: Group B (Dentin Bonding Agent) specimens cemented with crowns fabricated in direct technique showed the least amount of microleakage when compared with group A and group C. Group C (Dental Varnish) specimen showed comparatively more amount of microleakage than that of group B. Group A (control group) specimens showed the maximum amount of microleakage. CONCLUSION: The application of a single layer of Dental varnish appears to be of no significant benefit when compared to crowns cemented with the application of Dentin bonding agent on the tooth surface. The application of a single layer of Dentin bonding agent (Solobond M) and temporary crowns fabricated with direct technique may be of some benefit for crown preparations as an interim measure prior to the luting of final crown. PMID- 26266220 TI - Survival of Implants in Immediate Extraction Sockets of Anterior Teeth: Early Clinical Results. AB - BACKGROUND: The aims and objectives of this study were placement of implants in freshly extracted sockets of anterior teeth and to evaluate the implant stability, peri-implant radiolucency and gingival inflammation around implant over a short period of 30 months. MATERIALS AND METHODS: A total of 12 patients (8 male and 4 female), ranging in the age from 20 to 50 years, from March 2007 to June 2007, were evaluated for immediate implant placement into 22 fresh extraction sockets. Only maxillary and mandibular anterior teeth/roots (central incisors, lateral incisors and canines) were considered for replacement with implants. One piece implant with integrated abutment and integrated surface, non submerged, threaded and tapered at apical 5 mm, sand-blasted and acid etched surfaced implants (HI-TEC TRX-OP Implants of Life Care Company) were used. RESULTS: The mobility was not present in any of the implants at all the follow up visits. There were 2 implants at 6 month, 1 implant at 12 month, 1 implant at 18 month visits, showing peri-implant radiolucency at some sites at bone to implant contact site. Severe gingival inflammation was not observed in any of the implant site. At every follow-up visit, every implant met the criteria of success and none was found to be failed over a 30 months duration i.e. 100% success rate was achieved by implants in immediate extraction socket. CONCLUSION: The success rate of implant survival in this study was found 100%. These implants have fulfilled all the criteria of implant success and based on the defined criteria, the success rate of implants placed in immediate extraction sockets of anterior teeth compared favorably with the conventional implants. The early results of the present study showed that high survival rates with the implants in immediate extraction sockets can be achieved. PMID- 26266221 TI - Invitro Antifungal Evaluation of Denture Soft Liner Incorporated with Tea Tree Oil: A New Therapeutic Approach Towards Denture Stomatitis. AB - AIM: Adherence and colonization of candida on denture soft liners is the most important contributing factor in development of denture stomatitis. This invitro study is undertaken to investigate whether the incorporation of tea tree oil into denture soft liners would inhibit the growth of candida albicans. MATERIALS AND METHODS: Each 10 specimen disks incorporated with tea tree oil into soft liners (St) and without tea tree oil (S) were prepared. Both the tea tree oil daily. These disks were inoculated with candida albicans suspension for assessment of fungal growth and were rinsed with sterile water to remove loosely attached surface organisms. The attached yeasts were measured by inoculating them on saboraud's agar. Treated and control disks were stored in distilled water for 1, 30, 60 days and washed daily with wet cotton. Data between treated and control disks were compared by applying t-test. RESULTS: The mean colony forming units (CFU) per mm(2) for specimens without tea tree oil after water storage and wash with wet cotton for 1, 30 and 60 days was 7.1 * 10(6), 6.5 * 10(6), 6.8 * 10(6), respectively and for specimens with tea tree oil CFU decreased significantly to 2.1 * 10(6), 2.8 * 10(6), 3.1 * 10(6) after 1, 30 and 60 days. Treated disks were effective in controlling the growth of C.albicans for two months following water storage. CONCLUSION: Addition of tea tree oil to denture soft liner significantly reduced growth of C.albicans suggesting a new form of intra oral effective antifungal management for denture stomatitis. PMID- 26266222 TI - Oral Cysticercosis- A Diagnostic Dilemma. AB - Cysticercosis, a helminthic disease commonly seen in India, Latin America, Eastern Europe and Southern Africa, results from extraintestinal encystation of the larval form of Taenia solium. It is a condition in which man acts as intermediate host instead of definitive host. The most frequent sites of cysticercosis are subcutaneous layers, brain, muscles, heart, liver, lungs, and peritoneum. Oral cysticercosis is considered rare and cause cystic swellings or nodules in the mouth and a precise clinical diagnosis is not usually established. Here, we report a case of oral cysticercosis in a 32-year-old female occurring in the mentalis muscle presenting as asymptomatic nodule. PMID- 26266223 TI - Surgical Management of a Non-healing Intra-alveolar Root Fracture Associated with Pulpal Calcification and Root Resorption: A Case Report. AB - Radicular fractures are very challenging to address due to various complications like periodontal communication, increased mobility, and continued pulpal infection leading to necrosis and its long term sequelae like root resorption and pulp canal obliteration. This paper present a case of a long standing horizontal mid root fracture with root resorption and pulp canal obliteration, which was preserved functionally and aesthetically by surgical approach using MTA (mineral trioxide aggregate) and PRF (platelet rich fibrin). PMID- 26266224 TI - Retrieval of Iatrogenically Pushed Pulp Stone From Middle Third of Root Canal in Permanent Maxillary Central Incisor: A Case Report. AB - The pulp stones are the discrete nodular calcified masses commonly existing in coronal and occasionally in radicular pulp, placed freely, attached or embedded into the dentine. The present case report revealed the iatrogenic pushing of pulp stone and blockage of root canal that caused endodontic failure. The case enlightens the proper use of ultrasonic instruments with irrigating solutions to manage the calcifications in root canal for successful endodontic therapy. PMID- 26266225 TI - A Nonsyndromic Autosomal Dominant Oligodontia with A Novel Mutation of PAX9-A Clinical and Genetic Report. AB - Oligodontia is congenital absence of one or more teeth which has familial abnormality and attributable to various mutations or polymorphisms of genes often associated with malformative syndromes. The present case reports a rare case of non syndromic oligodontia in an 8-year-old girl with missing 14 permanent teeth excluding third molars in mixed dentition. It is a rare finding which has not been frequently documented in Indian children. Mutations in MSX1 and PAX9 have been described in families in which inherited oligodontia characteristically involves permanent incisors, lateral incisors, premolars and molars. Our study analysed one large family with dominantly inherited oligodontia clinically and genetically. This phonotype is distinct from oligodontia phenotypes associated with mutations in PAX9. Sequencing of the PAX9 revealed a novel mutation in the paired domain of the molecule. The multiple sequence alignment and SNP analysis of the PAX9 exon 2 revealed two mutations. PMID- 26266226 TI - Polymorphous Low Grade Adenocarcinoma of Retromolar Region - A Rare Case Report with Distinct Clinical Manifestations. AB - Polymorphous low grade adenocarcinoma (PLGA) is a rare, low-grade malignancy of minor salivary glands accounting for 2% of salivary gland tumours. The most common sites are palate (60%), lip, buccal mucosa, alveolar ridge and base of the tongue with retromolar region being very rare (0.5%). It is considered to be a low grade malignancy with indolent nature. Very few cases with metastatic spread to lymph nodes and lung have been reported in literature. This report of PLGA is a rare case presenting in an uncommon location (retromolar area) with suspected lymph node and lung metastases. PMID- 26266227 TI - An Unusual Complication with Use of Lignocaine: A Case Report. AB - Allergic responses to lignocaine (amide local anaesthesia) used in dentistry is extremely rare. It is widely used by Oral Maxillofacial surgeons to carry out various procedures safely, comfortably and efficiently. It is important for the practitioners to be aware that allergic reactions though very rare, can occur after injection of lignocaine intradermally for allergy testing. A proper diagnosis and management of such allergic reaction is very essential to avoid undesired consequences. We report a case of a 50-year-old male who suffered itching and generalized skin reaction within 5 minutes after administration of test dose of lignocaine intradermally for allergy testing. Clinical presentation, Diagnosis & management of such allergic reaction are discussed. As local anaesthetic agents are commonly used drugs in day to day practice clinicians are encouraged to be familiar with the presentation of various allergic reactions and there management. PMID- 26266228 TI - Primary Malignant Mixed Germ Cell Tumour with Squamous Cell Carcinoma of the Mandible; A Rare Entity. AB - Germ cell Tumours (GCT) are neoplasm derived from germ cells. GCT usually occurs inside the gonads. Extragonadal GCT's are rare. Most common GCT associated with head and neck region are the teratomas. Of the few teratomas found in the head and neck, malignant transformation of a teratomatous element is very uncommon, and primary bone involvement within the head and neck is even rare. We present a case of primary malignant mixed germ cell Tumour involving the mandible, the present case presented malignant transformation of the epithelial component showing foci of squamous cell carcinoma within the GCT. PMID- 26266229 TI - Rare Case of Spindle Cell Haemangioma. AB - Spindle cell haemangioma (SCH) is a benign vascular lesion which usually occurs on distal extremities. It was previously regarded as haemangioendothelioma and was initially perceived to be low grade angiosarcoma.They are characterized by cavernous blood vessels and spindle cell proliferation. It is now considered as a reactive lesion and conservative surgical excision is preferred treatment. Intraoral occurrence is rare; hence we present a case of SCH in a 33-year-old male that presented as a swelling below the tongue. Histopathology showed well circumscribed proliferating spindle cells attached to vessel walls, dilated vascular spaces. The lesion was positive for CD31 and CD34 markers suggesting it to be of endothelial cell origin. PMID- 26266230 TI - Primary Diffuse Large B-cell Lymphoma Arising in the Tongue Accompanied by Ataxia telangiectasia: A Case Report. AB - Ataxia-telangiectasia (AT) is a rare autosomal recessive disorder that is characterized by progressive cerebellar ataxia, telangiectasia, immunodeficiency, and a predisposition to leukemia/lymphoma. Here we report a rare case of lymphoma of the tongue accompanied by AT. Tumour extirpation was performed and diffuse large B-cell lymphoma was diagnosed following pathologic examination. A whole body survey showed no other enlarged lymph nodes or tumour. The female patient then received a modified dosage of COPAD (cyclophosphamide, vinblastine, pirarubicin, and prednisolone) plus rituximab to avoid severe complications. As of follow-up after 3 years and 5 months, she remains in complete remission. Patients showing AT need careful surveillance and long-term continuous follow-up. PMID- 26266231 TI - Aesthetic Management of Fluoresced Teeth with Ceramic Veneers and Direct Composite Bonding - An Overview and A Case Presentation. AB - Tooth discolouration is a common problem and affects people of all ages. Apart from the conventional treatment modalities for the same, newer options are available today with better techniques and materials. The present case report describes a 17-year-old girl who had stained and pitted teeth, attributable to dental fluorosis and she desired aesthetic treatment for the same. The pros and cons of all treatment options were carefully weighed and a multistep treatment process involving ceramic veneers and direct bonding were planned. The execution of the planned treatment yielded a good aesthetic and functional outcome. PMID- 26266232 TI - Juvenile Nasopharyngeal Angiofibroma Extending into the Oral Cavity: A Rare Entity. AB - Juvenile nasopharyngeal angiofibroma (JNA) is a rare vascular tumour which is benign but locally aggressive and occurs invariably in young and adolescent males. It seldom involves the oral cavity but has the tendency to invade the adjacent structures. Its characteristic features include slow progression, aggressive growth & an increased rate of persistence and recurrence due to its location in inaccessible areas. In literature, very few cases of JNA have been reported with extension into the oral cavity. Here, a case of JNA with extension into the oral cavity has been discussed who reported to our institute. PMID- 26266233 TI - Management of Radicular Cyst Using Platelet-Rich Fibrin & Iliac Bone Graft - A Case Report. AB - Radicular cyst is one of the most commonly occurring cyst in the oral cavity it is usually preceded by trauma or an infectious condition which is followed by enlargement. In recent times there are several treatment procedures that are being applied in order to improve the postoperative condition and to accelerate the process of healing and regeneration in the affected site. A 22-year-old patient reported to our OPD with the chief complaint of swelling on the left side of the face since 2-3 months, on investigating it was diagnosed as Radicular cyst which was initially treated by endodontic treatment of the involved tooth followed by enucleation of the cyst further an apicoectomy was done. Finally a PRF and iliac crest graft was placed for aesthetic rehabilitation with 21. PMID- 26266234 TI - Human Papilloma Virus (HPV) Induced Head & Neck Squamous Cell Carcinoma: A Comprehensive Retrospect. AB - Head and Neck Squamous Cell Carcinoma accounts for the sixth most common malignancy occurring worldwide with tobacco and alcohol being the two well established risk factors. In the recent years, substantial evidence has been obtained that Human Papilloma Virus (HPV) associated head and neck cancers are on the rise. This article provides an insight into the structure of HPV genome, molecular pathogenesis, detection methods and clinical implications of HPV positive Head and Neck Squamous Cell Carcinoma. PMID- 26266235 TI - Mitigation of Fluorosis - A Review. AB - Fluoride is required for normal development and growth of the body. It is found in plentiful quantity in environment and fluoride content in drinking water is largest contributor to the daily fluoride intake. The behaviour of fluoride ions in the human organism can be regarded as that of "double-edged sword". Fluoride is beneficial in small amounts but toxic in large amounts. Excessive consumption of fluorides in various forms leads to development of fluorosis. Fluorosis is major health problem in 24 countries, including India, which lies in the geographical fluoride belt. Various technologies are being used to remove fluoride from water but still the problem has not been rooted out. The purpose of this paper is to review the available treatment modalities for fluorosis, available technologies for fluoride removal from water and ongoing fluorosis mitigation programs based on literature survey. Medline was the primary database used in the literature search. Other databases included: PubMed, Web of Science, Google Scholar, WHO, Ebscohost, Science Direct, Google Search Engine, etc. PMID- 26266236 TI - OPN -Revisited. AB - Osteopontin (OPN), a matrix extracellular glyco-phosphoprotein is found in various tissues such as epithelium lined tissues, kidney, bone and teeth .It is also detected in all body fluids including blood and breast milk. OPN plays role in a number of physiological and pathologic events such as cell adhesion, migration and cell survival, angiogenesis, apoptosis, inflammation and wound healing. This review summarizes the current data of the biological activities of OPN in the development of tumour, its progression and metastasis. PMID- 26266237 TI - Partial Edentulism and its Correlation to Age, Gender, Socio-economic Status and Incidence of Various Kennedy's Classes- A Literature Review. AB - Partial edentulism, one or more teeth missing is an indication of healthy behaviour of dental practices in the society and attitude towards dental and oral care. The pattern of partial edentulism has been evaluated in many selected populations in different countries by different methods. Most of the studies have evaluated partial edentulism by surveying of Removable Partial Dentures (RPDs), patients visiting clinics, clinical records and population in particular locality. The objective of the study is to review the prevalence of partial edentulousness and its correlation to age,gender, arch predominance, socio economic factors and incidence of various Kennedy's Classes. Key observations drawn from the review are as below. There is no gender correlation for partial edentulism.Prevalence of partial edentulism is more common in mandibular arch than maxillary arch.Younger adults have more Class III and IV RPDs. Elders have more distal extension RPDs Class I and II. PMID- 26266239 TI - A Rare Case of Low Flow Vascular Malformation of Head and Neck Region Presenting with Multiple Phleboliths. PMID- 26266238 TI - Flowable Resin Composites: A Systematic Review and Clinical Considerations. AB - BACKGROUND: Little is known about flowable composite materials. Most literature mentions conventional composite materials at large, giving minimal emphasis to flowables in particular. This paper briefly gives an in depth insight to the multiple facets of this versatile material. AIM: To exclusively review the most salient features of flowable composite materials in comparison to conventional composites and to give clinicians a detailed understanding of the advantages, drawbacks, indications and contraindications based on composition and physical/mechanical properties. METHODOLOGY: DATA SOURCES: A thorough literature search from the year 1996 up to January 2015 was done on PubMed Central, The Cochrane Library, Science Direct, Wiley Online Library, and Google Scholar. Grey literature (pending patents, technical reports etc.) was also screened. The search terms used were "dental flowable resin composites". SEARCH STRATEGY: After omitting the duplicates/repetitions, a total of 491 full text articles were assessed. As including all articles were out of the scope of this paper. Only relevant articles that fulfilled the reviewer's objectives {mentioning indications, contraindications, applications, assessment of physical/mechanical/biological properties (in vitro/ in vivo /ex vivo)} were considered. A total of 92 full text articles were selected. CONCLUSION: Flowable composites exhibit a variable composition and consequently variable mechanical/ physical properties. Clinicians must be aware of this aspect to make a proper material selection based on specific properties and indications of each material relevant to a particular clinical situation. PMID- 26266240 TI - Use of the Open Coil Space Regainer for Tooth Movement Prior to Prosthodontic Treatment. PMID- 26266241 TI - Bilateral Paramolar Tubercles on the Distobuccal Surfaces of Mandibular Primary First Molars: A Rare Occurrence. PMID- 26266242 TI - Shear Bond Strength - New Reports. PMID- 26266243 TI - Successful Treatment of Idiopathic Eosinophilic Peritonitis by Oral Corticosteroid Therapy in a Continuous Ambulatory Peritoneal Dialysis Patient. AB - Eosinophilic peritonitis is a well-described complication of peritoneal dialysis and is often associated with either a reaction to the dialysis system constituent (tubing, sterilant or solution) or an underlying bacterial or fungal reaction. We report a case of eosinophilic peritonitis, which is treated by oral prednisone acetate therapy. A 43-year-old female patient developed end-stage renal disease and underwent continuous ambulatory peritoneal dialysis for 2.5 years. The patient received 2,000 ml of 1.5% dialysis solution (PD2) with three exchanges daily and 2,000 ml of 2.5% PDF overnight (PD2). She went to the consultation because of a constant turbid peritoneal dialysis effluent for 3 months without abdominal pain. Repeated peritoneal effluent samples showed an elevated white blood cell count of 500 cells/mm(3), with 87% eosinophils. The peripheral blood test revealed a white blood cell count of 3.8 * 10(9)/l, with 32.2% eosinophils. Etiology like bacterial and fungal infection was excluded by peritoneal fluid culture. Turbidness persisted in spite of diagnostic antibiotic treatment. Given the fact that we found a significant elevation of eosinophils in the peripheral blood and an absolute increase in the eosinophil count of >30/mm(3) in dialysis fluid (up to 400/mm(3) in our patient), obvious dialysate effluent turbidness, negative results of repeated peritoneal fluid cultures, inefficacy of antibiotic therapy, and negativity of serum tumor and immunological markers, we drew the conclusion that the patient had idiopathic eosinophilic peritonitis. Oral corticosteroid was administered at once (20 mg prednisone acetate daily), which was gradually weaned off and stopped over an 8-week period. Afterwards, the dialysis effluent became clear, and the cytological analysis showed that the white blood cell count decreased to 1 * 10(6)/l, with no eosinophils. This case reminds us that the diagnosis of eosinophilic peritonitis should be considered when repeated cultures are always negative and the turbidness of peritoneal dialysis effluent persists in spite of an antibiotic therapy. PMID- 26266244 TI - Peritoneal-Pleural Leaks Demonstrated by CT Peritoneography. AB - INTRODUCTION: Acute hydrothorax is an uncommon complication of peritoneal dialysis (PD). Currently, there is no specific diagnostic method. Although it is not a life-threatening complication, hydrothorax often requires interrupting or quitting PD. Misdiagnosis often leads to more serious consequences. CASE PRESENTATION: A 49-year-old woman (height 163 cm, weight 58 kg, BMI 21.82), who started PD 3 months previously, suddenly presented with acute dyspnea and a right pleural effusion. Blood routine examination, serum albumin and a series of laboratory tests were immediately performed. Except for the serum creatinine, all of the other tests were within normal range. Thoracentesis was performed to obtain pleural fluid specimens; there was also no evidence of a tumor or inflammation. Congestive heart failure, infection and hypoalbuminemia were excluded as well. Because PD-associated pleural leakage was suspected, computerized tomography (CT) peritoneography was performed next. The first CT scan showed that the CT value of pleural effusion was 6 Hounsfield units (HU). On the evening of the same day, 100 ml ionic contrast medium was mixed with 2 l dialysate and infused into the peritoneal cavity. The next morning, a CT scan was performed again. The CT value of pleural effusion at the same site increased to 40 HU. At the end, pleural leakage was clearly diagnosed. Subsequently, she received temporary hemodialysis and a small dose of automated PD. After 3 months, she successfully returned to PD without any recurrence of hydrothorax. CONCLUSION: Although similar case reports are not rare, this report provided a simple and effective method for diagnosing pleural leakage. Furthermore, noninvasive treatment of pleural effusion will also get a satisfactory outcome. PMID- 26266245 TI - Automated Peritoneal Dialysis is Suitable for Polycystic Kidney Disease Patients with End-Stage Renal Disease. AB - A female patient with polycystic kidney disease (PKD) was treated with automated peritoneal dialysis when she reached end-stage renal disease. The patient has been doing very well on automated peritoneal dialysis (APD) for almost 6 years without peritonitis or abdominal hernias. Intra-abdominal pressures are lower in the supine position than in an erect or sitting position. Larger volumes of dialysate are better tolerated while the patient is supine, as during nocturnal APD. Therefore, APD is an option of the renal replacement therapy for patients with PKD. PMID- 26266246 TI - Refractory Abdominal Pain in a Hemodialysis Patient. AB - Nonocclusive mesenteric ischemia (NOMI) is a rare disorder. Failure of an early diagnosis may cause progressive intestinal ischemia, leading to abdominal pain, sepsis, and death. Patients with end-stage renal disease are among the highest risk populations for developing this lethal complication. The key to a correct diagnosis at an early stage is a high index of suspicion in predisposed patients. In our case, we present a 62-year-old female undergoing maintenance hemodialysis for 8 years; she complained of abdominal pain after hemodialysis in the last 3 months; NOMI was suspected after a CT angiography. She partially recovered after multiple clinical interventions such as decreased ultrafiltration, an increased dose of low molecular-weight heparin and the use of vasoactive drugs. In conclusion, NOMI can be reversible if it is diagnosed as early as possible and after the necessary diagnostic measurements are initiated. PMID- 26266247 TI - Drug-Immune Thrombocytopenia with Thrombosis versus Heparin-Induced Thrombocytopenia: A Critical Clinical Controversy. AB - Heparin-induced thrombocytopenia (HIT) is a type of drug-induced immune thrombocytopenia (DITP). DITP is a rare and challenging clinical issue, especially when it is associated with thrombosis. A 62-year-old woman was admitted to our institution with end-stage renal failure. She received heparin for hemodialysis. Six days later, she became febrile and was treated with vancomycin and amikacin antibiotics. Two days after starting the vancomycin, she developed severe thrombocytopenia with extensive gangrenous deep vein thrombosis in her right leg, which required a below-the-knee amputation. The HIT test yielded positive results when heparin was already stopped, but her platelet count did not regenerate even after 3 months of heparin-free treatment. Courses of vancomycin treatment were given during several febrile episodes over the long period of severe thrombocytopenia. The patient was given both anti-immune thrombocytopenia and anticoagulant treatments because of both severe persistent thrombocytopenia and recurrent thrombotic episodes. The patient died as a result of severe thrombocytopenia, recurrent infection, and blood loss from the amputation site. Vancomycin is known to cause DITP, thrombosis, and immune complexes. DITP is a bleeding disorder, whereas HIT is a controversial thrombotic disorder. HIT tests can be influenced by cross-reacting antibodies and many other factors. Thus, there is no single method that can be considered 100% effective in confirming the HIT diagnosis. Anticoagulants must be used with great caution in patients with suspected DITP. Treatment of HIT-positive cases requires both clinical correlation and experience rather than reliance on HIT tests alone. PMID- 26266248 TI - Improvement in Gemcitabine-Induced Thrombotic Microangiopathy with Rituximab in a Patient with Ovarian Cancer: Mechanistic Considerations. AB - Gemcitabine is a potent and widely used anticancer drug. We report a case of gemcitabine-induced thrombotic microangiopathy (GCI-TMA), a known but not widely recognized complication of gemcitabine use, and our experience of treating GCI TMA with rituximab. A 74-year-old woman was referred to our clinic for an evaluation of worsening renal function. She has recently been treated for ovarian cancer (diagnosed in 2011) with surgery (tumor debulking and bilateral salpingo oophorectomy) along with cisplatin chemotherapy in 2012, followed by carboplatin/doxorubicin in 2013 and recent therapy for resistant disease with gemcitabine. Laboratory tests showed anemia, normal platelets and elevated lactate dehydrogenase. A peripheral smear revealed numerous schistocytes, and a kidney biopsy showed acute as well as chronic TMA. The patient continued on gemcitabine therapy, and treatment with plasma exchange was started. Since there was no response to treatment even after 5 sessions of plasma exchange, one dose of rituximab was given, which was associated with a drop in the creatinine level to 2 mg/dl. The pathogenesis of renal injury could be the effect of direct injury to the endothelium mediated by cytokines. Usual treatment includes withdrawing the drug and initiation of treatment with plasmapheresis with or without steroids. In cases resistant to plasmapheresis, treatment with rituximab can be tried. The mechanism of action of rituximab might be due to the reduced production of B-cell-dependent cytokines that drive endothelial dysfunction by depleting B cells. Patients receiving gemcitabine chemotherapy should be monitored for the development of TMA, and early treatment with plasma exchange along with rituximab might benefit these patients who already have a bad prognosis. PMID- 26266249 TI - ANCA-Negative Pauci-Immune Crescentic Glomerulonephritis Linked with Non-Small Cell Carcinoma of the Lung. AB - The association between malignancy and glomerular disease has been appreciated for decades [Baschinsky et al., Am J Kidney Dis 2000;36:E24]. Several types of glomerular injury in patients with cancer have been recognized [Morikawa et al., CEN Case Rep 2013;2:158-164; Baschinsky et al., Am J Kidney Dis 2000;36:E24]. The most common association is between nephrotic syndrome and carcinoma [Baschinsky et al., Am J Kidney Dis 2000;36:E24]. We report a case of anti-neutrophil cytoplasmic antibody-negative crescentic glomerulonephritis associated with lung cancer. To the best of our knowledge, only 1 other case of ANCA-negative pauci immune crescentic glomerulonephritis associated with lung cancer has been reported [Baschinsky et al., Am J Kidney Dis 2000;36:E24]. PMID- 26266251 TI - A New Era of Laparoscopic Revision of Kasai Portoenterostomy for the Treatment of Biliary Atresia. AB - PURPOSE: Kasai portoenterostomy is the standard therapy for biliary atresia (BA). If Kasai is unsuccessful, there is controversy over whether revision of Kasai restores adequate biliary drainage. Although there are several reports of laparoscopic Kasai (Lap-Kasai), none has described laparoscopic revision (Lap revision). The purposes of this study were to evaluate the feasibility and efficacy of Lap-revision. METHODS: 65 patients underwent open Kasai between November 2001 and November 2013, and 12 patients underwent Lap-Kasai between December 2013 to January 2015. The indications for revision included bile flow cessation and recurrent cholangitis. Clinical data were compared between open and laparoscopic revisions of Kasai. RESULTS: Open revision of Kasai was performed in 20 patients after open Kasai, and Lap-revision was performed in 4 patients after Lap-Kasai. Lap-revision was completed without conversion or major complication in any patient. The bilirubin level was normalized by Lap-revision in all four patients, and three of them were alive with their native liver. Open and laparoscopic revisions of Kasai were comparable in terms of the operation time, blood loss, and surgical outcomes. CONCLUSION: Lap-revision is a feasible and effective method for the treatment of BA and might herald a new era for the treatment of this disease. PMID- 26266250 TI - Genetics of Human and Canine Dilated Cardiomyopathy. AB - Cardiovascular disease is a leading cause of death in both humans and dogs. Dilated cardiomyopathy (DCM) accounts for a large number of these cases, reported to be the third most common form of cardiac disease in humans and the second most common in dogs. In human studies of DCM there are more than 50 genetic loci associated with the disease. Despite canine DCM having similar disease progression to human DCM studies into the genetic basis of canine DCM lag far behind those of human DCM. In this review the aetiology, epidemiology, and clinical characteristics of canine DCM are examined, along with highlighting possible different subtypes of canine DCM and their potential relevance to human DCM. Finally the current position of genetic research into canine and human DCM, including the genetic loci, is identified and the reasons many studies may have failed to find a genetic association with canine DCM are reviewed. PMID- 26266252 TI - A Novel Noninvasive Method for Measuring Fatigability of the Quadriceps Muscle in Noncooperating Healthy Subjects. AB - BACKGROUND: Critical illness is associated with muscle weakness leading to long term functional limitations. OBJECTIVES: To assess the reliability of a novel method for evaluating fatigability of the quadriceps muscle in noncooperating healthy subjects. METHODS: On two occasions, separated by seven days, nonvoluntary isometric contractions (twitch and tetanic) of the quadriceps femoris muscle evoked by transcutaneous electrical muscle stimulation were recorded in twelve healthy adults. For tetanic contractions, the Fatigue Index (ratio of peak torque values) and the slope of the regression line of peak torque values were primary outcome measures. For twitch contractions, maximum peak torque and rise time were calculated. Relative (intraclass correlation, ICC3.1) and absolute (standard error of measurement, SEM) reliability were assessed and minimum detectable change was calculated using a 95% confidence interval (MDC95%). RESULTS: The Fatigue Index (ICC3.1, 0.84; MDC95%, 0.12) and the slope of the regression line (ICC3.1, 0.99; MDC95%, 0.03) showed substantial relative and absolute reliability during the first 15 and 30 contractions, respectively. CONCLUSION: This method for assessing fatigability of the quadriceps muscle produces reliable results in healthy subjects and may provide valuable data on quantitative changes in muscle working capacity and treatment effects in patients who are incapable of producing voluntary muscle contractions. PMID- 26266253 TI - Effect of Fluoride-Modified Titanium Surface on Early Adhesion of Irradiated Osteoblasts. AB - OBJECTIVE: The present study aimed to investigate the effect of fluoride-modified titanium surface on adhesion of irradiated osteoblasts. MATERIALS AND METHODS: Fluoride-modified surface was obtained and the morphology, roughness, and chemical composition of the surface were evaluated by scanning electron microscopy, atomic force microscopy, and X-ray photoelectron spectroscopy, respectively. The adhesion of irradiated osteoblast-like cells, in terms of number, area, and fluorescence intensity on the titanium surface, was evaluated using immunofluorescence staining. RESULTS: Numerous nanosize pits were seen only in the F-TiO surface. The pits were more remarkable and uniform on F-TiO surface than on TiO surface; however, the amplitude of peaks and bottoms on F-TiO surface appeared to be smaller than on TiO surface. The Sa value and Sdr percentage of TiO surfaces were significantly higher than those of F-TiO surface. The concentrations of main elements such as titanium, oxygen, and carbon were similar on both surfaces. The number of irradiated osteoblasts adhered on the control surface was larger than on fluoride-modified surface. Meanwhile, the cells on the fluoride-modified surface formed more actin filaments. CONCLUSIONS: The fluoride modified titanium surface alters the adhesion of irradiated osteoblasts. Further studies are needed to investigate the proliferation, differentiation, maturation, gene expression, and cytokine production of irradiated osteoblasts on fluoride modified titanium surface. PMID- 26266254 TI - Prevalence and Prognostic Value of Early Repolarization in Low Risk Surgical Patients. AB - Recent epidemiological studies documented that early repolarization may be associated with increased risk of serious cardiac events, including cardiac death. Little is known about the prognostic significance of this pattern in low risk surgical patients. This retrospective study included 3028 patients over 18 years of age and with ASA class I and II risk, undergoing noncardiac elective surgery. We followed the patients for one year. Early repolarization in preoperative ECG was found in 219 patients (7.2%) and patients with early repolarization were more likely to be male and younger. Newly observed cardiac events were significantly higher in the early repolarization group (1.37% versus 0.21%; P = 0.003). Multivariate regression analysis reveals that early repolarization (odds ratio: 6.019, P = 0.013) significantly increased newly observed cardiac events. Our retrospective study suggests that low risk surgical patients with early repolarization have statistically higher opportunity of newly observed cardiac events within one year after surgery. PMID- 26266255 TI - The Impact of Endometriosis on the Health of Women. PMID- 26266256 TI - Sepsis and AKI in Clinical Emergency Room Patients: The Role of Urinary NGAL. AB - BACKGROUND: Few studies have investigated the predictive properties of urinary (u) NGAL as an AKI marker in septic population. OBJECTIVES: This study evaluated the efficacy of uNGAL as predictor of AKI and death in septic patients admitted to the clinical emergency room (ER). METHODOLOGY: We prospectively studied patients with sepsis admitted to the ER. Urine was analyzed for NGAL within the first 24 hours after admission (classified as NGAL1), between 24 and 48 h (NGAL2), and at moment of AKI diagnosis (NGAL3). RESULTS: Among 168 septic patients admitted to ER, 72% developed AKI. The uNGAL and its relationship with creatinine (Cr) were high in septic patients but statistically higher in those with sepsis and AKI. The uNGAL1 and uNGAL2, as well as uNGAL1/uCr1 and uNGAL2/uCr2, were good predictors for AKI (AUC-ROC 0.73, 0.70, 0.77, and 0.84, resp.). The uNGAL1 and uNGAL1/uCr1 were poor predictors for death (AUC-ROC 0.66 and 0.68, resp.), whereas uNGAL2 and uNGAL2/uCr2 were better predictors (AUC-ROC 0.70 and 0.81, resp.). CONCLUSION: The uNGAL is highly sensitive but nonspecific predictor of AKI and death in septic patients admitted into ER. PMID- 26266257 TI - Expression Profile of Sonic Hedgehog Pathway Members in the Developing Human Fetal Brain. AB - The Sonic Hedgehog (SHH) pathway plays a central role in the developing mammalian CNS. In our study, we aimed to investigate the spatiotemporal SHH pathway expression pattern in human fetal brains. We analyzed 22 normal fetal brains for Shh, Patched, Smoothened, and Gli1-3 expression by immunohistochemistry. In the telencephalon, strongest expression of Shh, Smoothened, and Gli2 was found in the cortical plate (CP) and ventricular zone. Patched was strongly upregulated in the ventricular zone and Gli1 in the CP. In the cerebellum, SHH pathway members were strongly expressed in the external granular layer (EGL). SHH pathway members significantly decreased over time in the ventricular and subventricular zone and in the cerebellar EGL, while increasing levels were found in more superficial telencephalic layers. Our findings show that SHH pathway members are strongly expressed in areas important for proliferation and differentiation and indicate a temporal expression gradient in telencephalic and cerebellar layers probably due to decreased proliferation of progenitor cells and increased differentiation. Our data about the spatiotemporal expression of SHH pathway members in the developing human brain serves as a base for the understanding of both normal and pathological CNS development. PMID- 26266258 TI - Cardamonin Regulates miR-21 Expression and Suppresses Angiogenesis Induced by Vascular Endothelial Growth Factor. AB - Cardamonin has promising potential in cancer prevention and therapy by interacting with proteins and modifying the expressions and activities, including factors of cell survival, proliferation, and angiogenesis. In our precious study, we have demonstrated that cardamonin suppressed vascular endothelial growth factor- (VEGF-) induced angiogenesis as evaluated in the mouse aortic ring assay. It is also known that microRNAs (miRNAs) play important roles in angiogenesis. Herein, we hypothesized whether antiangiogenesis effect of cardamonin in human umbilical vein endothelial cells (HUVECs) triggered by VEGF was associated with miRNAs. We found that cardamonin reduced the miR-21 expression induced by VEGF in HUVECs. Treatment with miR-21 mimics abolished the effects of cardamonin on VEGF induced cell proliferation, migration, and angiogenesis in HUVECs. However, treatment with miR-21 inhibitors presented the opposite effects, indicating the vital role of miR-21 in this process. Our study provides a new insight of the preliminary mechanism of anti-VEGF-induced angiogenesis by cardamonin in HUVECs. PMID- 26266259 TI - Radiologic Evaluation of Compressive Osseointegration for the Fixation of Reconstruction Prostheses after Tumor Resection. AB - OBJECTIVE: In pursuance of thoroughly understanding and facilitating the evaluation of the radiological changes in the preloaded bone by Compliant Pre Stress osseointegration (Compress Biomet, Warsaw, Indiana) a new staging method was created depicting four stages. METHODS: Two cohorts (10 and 17 patients resp., not-receiving and receiving chemotherapy) were compared in terms of progression of osseointegration. Based on the changes at the bone-metal interface seen on rontgenorgrams four stages were defined: stage 0: immediate postoperative status, no ingrowth, or noncalcified callus; stage 1: early mineralization, calcified callus; stage 2: mature mineralization; and stage 3: hypertrophy at the level of the pins. RESULTS: There were no significant differences between the two cohorts. Group 2, which was significantly younger than group 1 (p < 0.001), presented a delayed initial rate of bone formation and reached stage 1 at 6 months instead of 3 months like group 1. The children from the group 2 demonstrated a visible rebound ingrowth. CONCLUSION: Despite the fact that the staging fails to demonstrate a statistical difference, it is rather simple and can be used for future studies. PMID- 26266260 TI - Comparison of the Effect of Vaginal Zataria multiflora Cream and Oral Metronidazole Pill on Results of Treatments for Vaginal Infections including Trichomoniasis and Bacterial Vaginosis in Women of Reproductive Age. AB - Effect of Zataria multiflora on bacterial vaginosis and Trichomonas vaginalis is shown in vivo and in vitro. We compare the effectiveness of Zataria multiflora cream and oral metronidazole pill on results of treatment for vaginal infections including Trichomonas and bacterial vaginosis; these infections occur simultaneously. The study included 420 women with bacterial vaginosis, Trichomonas vaginalis, or both infections together, who were randomly divided into six groups. Criteria for diagnosis were wet smear and Gram stain. Vaginal Zataria multiflora cream and placebo pill were administered to the experiment groups; the control group received oral metronidazole pill and vaginal placebo cream. Comparison of the clinical symptoms showed no significant difference in all three vaginitis groups receiving metronidazole pill and vaginal Zataria multiflora cream. However, comparison of the wet smear test results was significant in patients with trichomoniasis and bacterial vaginosis associated with trichomoniasis in the two treatment groups (p = 0.001 and p = 0.01). Vaginal Zataria multiflora cream had the same effect of oral metronidazole tablets in improving clinical symptoms of all three vaginitis groups, as well as the treatment for bacterial vaginosis. It can be used as a drug for treatment of bacterial vaginosis and elimination of clinical symptoms of Trichomonas vaginitis. PMID- 26266261 TI - MicroRNA and Cardiovascular Disease. PMID- 26266262 TI - Right-to-Left Shunt Does Not Increase the Incidence of Silent Lacunar Infarcts in Patients with Migraine. AB - Right-to-left shunt (RLS) is associated with cryptogenic stroke and migraine. Herein we investigated the relationship between RLS and silent lacunar infarcts in patients with migraine. A total of 263 patients with migraine who met eligibility criteria were enrolled from January 2010 to December 2011, among which 127 subjects fell into RLS group. Baseline demographics were comparable between RLS and non-RLS groups (P > 0.05). The incidence of silent lacunar infarcts in RLS group was not significantly different from that of the non-RLS group (25.2% versus 21.3%, P > 0.05). Furthermore, we found that the incidence of silent lacunar infarcts in permanent and latent RLS subgroups was comparable with non-shunt RLS subgroup (28.6% versus 24% versus 21.3%, P > 0.05). Similarly, the incidence of silent lacunar infarcts in the non-RLS group, mild-shunt group, and large-shunt group was also comparable (21.3% versus 23.8% versus 29.3%, P > 0.05). In addition, RLS did not increase the incidence of silent lacunar infarcts in migraine patients with elder age (< 50 years age group: 15.8% versus 17.9%; >= 50 years age group: 53.1% versus 37.5%, both P > 0.05). In conclusion, RLS does not increase the incidence of silent lacunar infarcts in patients with migraine. Further prospective studies are warranted to validate this finding. PMID- 26266263 TI - Magnetic Resonance Imaging of Atherosclerosis Using CD81-Targeted Microparticles of Iron Oxide in Mice. AB - The goal of this study is to investigate the feasibility of using CD81- (Cluster of Differentiation 81 protein-) targeted microparticles of iron oxide (CD81-MPIO) for magnetic resonance imaging (MRI) of the murine atherosclerosis. CD81-MPIO and IgG- (Immunoglobulin G-) MPIO were prepared by covalently conjugating, respectively, with anti-CD81 monoclonal and IgG antibodies to the surface of the tosyl activated MPIO. The relevant binding capability of the MPIO was examined by incubating them with murine bEnd.3 cells stimulated with phenazine methosulfate (PMS) and its effect in shortening T2 relaxation time was also examined. MRI in apolipoprotein E-deficient mice was studied in vivo. Our results show that CD81 MPIO, but not IgG-MPIO, can bind to the PMS-stimulated bEnd.3 cells. The T2 relaxation time was significantly shortened for stimulated bEnd.3 cells when compared with IgG-MPIO. In vivo MRI in apolipoprotein E-deficient mice showed highly conspicuous areas of low signal after CD81-MPIO injection. Quantitative analysis of the area of CD81-MPIO contrast effects showed 8.96- and 6.98-fold increase in comparison with IgG-MPIO or plain MPIO, respectively (P < 0.01). Histological assay confirmed the expression of CD81 and CD81-MPIO binding onto atherosclerotic lesions. In conclusion, CD81-MPIO allows molecular assessment of murine atherosclerotic lesions by magnetic resonance imaging. PMID- 26266265 TI - Biometrics and Biosecurity 2014. PMID- 26266266 TI - Skin Regeneration, Repair, and Reconstruction. PMID- 26266267 TI - Beyond Culture and Language: Access to Diabetes Preventive Health Services among Somali Women in Norway. AB - Despite the high prevalence of type 2 diabetes in some immigrant and refugee communities in Norway, there is very little information available on their utilization of diabetes prevention interventions, particularly for women from Somali immigrant communities. A qualitative study of 30 Somali immigrant women aged 25 years and over was carried out in the Oslo area. Unstructured interviews were used to explore women's knowledge of diabetes, their access to preventive health facilities, and factors impeding their reception of preventive health programs targeted for the prevention of type 2 diabetes. The study participants were found to have a good knowledge of diabetes. They knew that a sedentary lifestyle and unhealthy diet are among the risk factors for diabetes. Regardless of their knowledge, participants reported a sedentary lifestyle accompanied with the consumption of an unhealthy diet. This was attributed to a lack of access to tailored physical activity services and poor access to health information. Considering gender-exclusive training facilities for Somali immigrant women and others with similar needs, in addition to access to tailored health information on diet, may encourage Somali women to adopt a healthy lifestyle, and it will definitely contribute to a national strategy for the prevention of diabetes. PMID- 26266268 TI - Type 1 Diabetes Modifies Brain Activation in Young Patients While Performing Visuospatial Working Memory Tasks. AB - In recent years, increasing attention has been paid to the effects of Type 1 Diabetes (T1D) on cognitive functions. T1D onset usually occurs during childhood, so it is possible that the brain could be affected during neurodevelopment. We selected young patients of normal intelligence with T1D onset during neurodevelopment, no complications from diabetes, and adequate glycemic control. The purpose of this study was to compare the neural BOLD activation pattern in a group of patients with T1D versus healthy control subjects while performing a visuospatial working memory task. Sixteen patients and 16 matched healthy control subjects participated. There was no significant statistical difference in behavioral performance between the groups, but, in accordance with our hypothesis, results showed distinct brain activation patterns. Control subjects presented the expected activations related to the task, whereas the patients had greater activation in the prefrontal inferior cortex, basal ganglia, posterior cerebellum, and substantia nigra. These different patterns could be due to compensation mechanisms that allow them to maintain a behavioral performance similar to that of control subjects. PMID- 26266264 TI - Animal Models for the Study of Rodent-Borne Hemorrhagic Fever Viruses: Arenaviruses and Hantaviruses. AB - Human pathogenic hantaviruses and arenaviruses are maintained in nature by persistent infection of rodent carrier populations. Several members of these virus groups can cause significant disease in humans that is generically termed viral hemorrhagic fever (HF) and is characterized as a febrile illness with an increased propensity to cause acute inflammation. Human interaction with rodent carrier populations leads to infection. Arenaviruses are also viewed as potential biological weapons threat agents. There is an increased interest in studying these viruses in animal models to gain a deeper understating not only of viral pathogenesis, but also for the evaluation of medical countermeasures (MCM) to mitigate disease threats. In this review, we examine current knowledge regarding animal models employed in the study of these viruses. We include analysis of infection models in natural reservoirs and also discuss the impact of strain heterogeneity on the susceptibility of animals to infection. This information should provide a comprehensive reference for those interested in the study of arenaviruses and hantaviruses not only for MCM development but also in the study of viral pathogenesis and the biology of these viruses in their natural reservoirs. PMID- 26266269 TI - Microbiome and Asthma: What Have Experimental Models Already Taught Us? AB - Asthma is a chronic inflammatory disease that imposes a substantial burden on patients, their families, and the community. Although many aspects of the pathogenesis of classical allergic asthma are well known by the scientific community, other points are not yet understood. Experimental asthma models, particularly murine models, have been used for over 100 years in order to better understand the immunopathology of asthma. It has been shown that human microbiome is an important component in the development of the immune system. Furthermore, the occurrence of many inflammatory diseases is influenced by the presence of microbes. Again, experimental models of asthma have helped researchers to understand the relationship between the microbiome and respiratory inflammation. In this review, we discuss the evolution of murine models of asthma and approach the major studies involving the microbiome and asthma. PMID- 26266271 TI - Numerical Algorithm for Delta of Asian Option. AB - We study the numerical solution of the Greeks of Asian options. In particular, we derive a close form solution of Delta of Asian geometric option and use this analytical form as a control to numerically calculate Delta of Asian arithmetic option, which is known to have no explicit close form solution. We implement our proposed numerical method and compare the standard error with other classical variance reduction methods. Our method provides an efficient solution to the hedging strategy with Asian options. PMID- 26266270 TI - Aeromonas salmonicida Infection Only Moderately Regulates Expression of Factors Contributing to Toll-Like Receptor Signaling but Massively Activates the Cellular and Humoral Branches of Innate Immunity in Rainbow Trout (Oncorhynchus mykiss). AB - Toll-like receptors (TLRs) are known to detect a defined spectrum of microbial structures. However, the knowledge about the specificity of teleost Tlr factors for distinct pathogens is limited so far. We measured baseline expression profiles of 18 tlr genes and associated signaling factors in four immune-relevant tissues of rainbow trout Oncorhynchus mykiss. Intraperitoneal injection of a lethal dose of Aeromonas salmonicida subsp. salmonicida induced highly increased levels of cytokine mRNAs during a 72-hour postinfection (hpi) period. In contrast, only the fish-specific tlr22a2 and the downstream factor irak1 featured clearly increased transcript levels, while the mRNA concentrations of many other tlr genes decreased. Flow cytometry quantified cell trafficking after infection indicating a dramatic influx of myeloid cells into the peritoneum and a belated low level immigration of lymphoid cells. T and B lymphocytes were differentiated with RT-qPCR revealing that B lymphocytes emigrated from and T lymphocytes immigrated into head kidney. In conclusion, no specific TLR can be singled out as a dominant receptor for A. salmonicida. The recruitment of cellular factors of innate immunity rather than induced expression of pathogen receptors is hence of key importance for mounting a first immune defense against invading A. salmonicida. PMID- 26266272 TI - Smart branched polymer drug conjugates as nano-sized drug delivery systems. AB - Polymer-drug conjugates represent excellent nanopharmaceutical candidates, as they offer multiple advantages related to their intrinsic characteristics. Many of the said characteristics are provided by the covalent bonding between the drug and the polymer. However, their clinical development has been slow and only one polymer-drug conjugate has reached the market, thus there remains an urgent need for the development of new and smart polymeric systems. Desirable characteristics of these new systems include higher molecular weight and degree of homogeneity, predictable conformations in solution, multivalency, and increased drug loading capacity, amongst others. With these aims in mind, branched polymers are ideal candidates due to their unique rheological, mechanical, and biomedical properties derived from their structure, inaccessible for linear polymers. Within this review, the synthetic strategies developed and the main efforts towards branched polymer implementation as carriers for polymer-drug conjugates will be addressed. PMID- 26266273 TI - Producing a road map that enables plants to cope with future climate change. PMID- 26266274 TI - Answer to comment. PMID- 26266275 TI - Retraction notice to "Clinical effectiveness of neoadjuvant chemotherapy in advanced gastric cancer: An updated meta-analysis of randomized controlled trials" [Eur J Surg Oncol 40 (10) (October 2014) 1321-1330]. PMID- 26266276 TI - Misleading acute promyelocytic leukemia morphology. PMID- 26266277 TI - Response to Dr. Richard Belley MD, CCFP, B.Sc; Dr. Dominique Buteau MD, CCFP(EM); Dr. Marie-Ludivine Chateau-Degat PhD. PMID- 26266278 TI - Reply. PMID- 26266279 TI - Sir Terry Pratchett: shaking hands with Death. PMID- 26266280 TI - Author response:. PMID- 26266281 TI - Letter to the Editor: Abrupt CMS Decision May Threaten Hundreds of Thousands of Wound Care Patients With Potential Limb Loss. PMID- 26266282 TI - Successful Pedicled Anterolateral Thigh Flap Reconstruction for a Recurrent Ischial Pressure Ulcer: A Case With Multiple Recurrences Over a 7-year Follow-up. AB - Ischial pressure ulcers are difficult ulcers to treat and have a low treatment success rate compared to sacral and trochanteric ulcers; regional flap failure further complicates the treatment. Reported here is a case of a 65-year-old man who experienced a spinal injury with paraplegia due to trauma 20 years ago. The patient experienced a recurrent ischial ulcer since 2007, and underwent several types of flap reconstruction with poor outcomes over a 7-year period. Therefore, the chosen intervention was a pedicled anterolateral thigh (pALT) fasciocutaneous flap reconstruction for the ischial ulcer via a subcutaneous route. Over the 10 month follow-up, the recurrent ischial ulcer healed without wound dehiscence. Island pALT reconstruction appears to be an alternative technique for treating recurrent ischial pressure ulcers. Though reconstruction of ischial ulcers via the pALT technique has been described previously, this may be the first case report to describe pALT flap in a patient with recurrent ischial ulcers after failed reconstructions using a gluteus maximus flap, V-Y advancement flap, and hatchet flap.Ischial pressure ulcers are difficult to treat and have a low treatment success rate1 compared to sacral and trochanteric ulcers. In addition, there are many different techniques that can be used to treat ischial pressure ulcers, including primary wound closure, gluteus maximus flaps, V-Y advancement flaps, or inferior gluteal artery perforator flaps. However, several experts have recently described using the pedicled anterolateral thigh (pALT) flap for reconstruction of recurrent ischial pressure ulcers.1,2 In the presented case, the authors followed a single patient with paraplegia with a recurrent ischial ulcer who had undergone several types of wound treatment over a 7-year period. The indurated ulcer was ultimately resolved by pALT reconstruction. PMID- 26266283 TI - New species of Rhyacodrilus (Annelida: Clitellata: Rhyacodrilinae) of North America, with re-description of R. sodalis (Eisen, 1879). AB - Six new Nearctic species of the aquatic oligochaete genus Rhyacodrilus (Annelida, Clitellata, Rhyacodrilinae), are described, five (R. saelonae sp. n., R. quileuticus sp. n., R. clio sp. n., R. alcyoneus sp. n. and R. longichaeta sp. n.) from western and one (R. propiporus sp. n.) from eastern North America. The taxonomy of the most common Rhyacodrilus species reported in the Nearctic region has been based largely on chaetal characters, which has generated certain confusion. The new species give a new perspective on the genus Rhyacodrilus in North America, suggesting a much higher diversity than previously expected. The description of R. longichaeta sp. n. questions the taxonomic status of R. montana (Brinkhurst), which is here regarded as species inquirenda. The taxonomic status of R. sodalis (Eisen) is discussed based on characters of the reproductive system, the existing Lake Tahoe neotype series is invalidated, and a neotype is described from Eisen's type locality. Based on the discussion of the characters of the genus Rhyacodrilus, the genus Stochidrilus Martinez-Ansemil et al. is proposed as a junior synonym of that genus. The presence of the widely reported species R. coccineus has not been confirmed in the study collections, although the species requires a sound revision. A key to the species bearing hair chaetae is provided, based mainly on features of the reproductive system. PMID- 26266284 TI - Typtonomenaeusformosanus gen. et sp. nov., a new sponge-associated pontoniine shrimp (Crustacea: Decapoda: Palaemonidae: Pontoniinae) from northern Taiwan. AB - A new genus and species of sponge-associated pontoniine shrimps (Crustacea: Decapoda: Palaemonidae: Pontoniinae) is described from northern part of Formosa Island (Taiwan). The new species can be clearly recognized by convex robust nail like apices on dactyli of both pereiopods II--a unique morphological structure among pontoniine shrimps. Morphological differences from all known sponge associated pontoniine genera are discussed. PMID- 26266285 TI - A new species of the spider genus Taczanowskia (Araneae, Araneidae) from Mexico. AB - A new species of the spider genus Taczanowskia, T. gustavoi n. sp. is described from Chiapas, Mexico. This finding extends the distribution of Taczanowskia species, hitherto known only from South America to Southern Mexico. T. gustavoi n. sp. can be differentiated from all other species in this genus by having more than six tubercles in the dorsum of its opisthosoma. This species is included in an earlier determination key for all previously known Taczanowskia species. PMID- 26266286 TI - A new species and records of Diolenius Thorell, 1870 (Araneae: Salticidae) from New Guinea. AB - Diolenius sarniensis sp. nov. is recorded, described and illustrated from New Guinea. PMID- 26266287 TI - Three new species of Pauropoda (Myriapoda) from Brazil with description of a new genus in Diplopauropodidae, Adelphopauropus. AB - Three new species of Pauropoda are described from Brazil, Allopauropus prolongus n.sp. and Decapauropus glomeratus n.sp. in Pauropodidae, and Adelphopauropus ichtyematos n. gen., n. sp. in Diplopauropodidae. PMID- 26266288 TI - Lethocerus patruelis (Stal, 1855) in Italy: a recent introduction or a natural westward spread? (Hemiptera: Heteroptera: Nepomorpha: Belostomatidae). AB - The paper provides new records and a critical review of the previous citations of Lethocerus patruelis (Stal, 1855) from Italy. The status of the species in Italy, and whether its presence can be related to a recent introduction or to a natural westward spread, is discussed, but further observations are needed to assess its effective status in the country. The dates of description for this species and of L. niloticus (Stal, 1855) are corrected, since they have up to the present time been incorrectly stated as 1854. PMID- 26266289 TI - Two new species of Fibuloides (Lepidoptera: Tortricidae) from eastern Thailand. AB - Two new species of Fibuloides are described from eastern Thailand: F. tratensis Jaikla and Pinkaew, n.sp., and F. bulla Jaikla and Pinkaew, n.sp. Males of F. tratensis have modified labial palpi with specialized scales that have not been reported for other Tortricidae. Descriptions and illustrations of adults and genitalia are provided for the two new species collected from Trat Agroforestry Research and Training Station, eastern Thailand. PMID- 26266290 TI - A note on Conchodytes kempi Bruce 1989 (Crustacea, Palaemonidae, Pontoniinae), with the designation of C. kempoides sp. nov.. PMID- 26266291 TI - Gyraulus elenae sp. n.--a new Planorbid snail from Eastern Turkey (Mollusca: Gastropoda: Planorbidae). PMID- 26266292 TI - Rusingeria nom. nov, a new substitute name for Usingeria Coetzee & Segerman, 1992 (Hemiptera: Heteroptera: Cimicidae). AB - Rusingeria nom. nov. is established as a new substitute name for Usingeria Coetzee & Segerman, 1992 (Hemiptera: Heteroptera: Cimicidae), which is junior homonym of Usingeria Schouteden, 1952 (Hemiptera: Heteroptera: Aradidae). The following new combination is proposed: Rusingeria transvaalensis (Coetzee & Segerman, 1992), comb. nov., for Usingeria transvaalensis Coetzee & Segerman, 1992. PMID- 26266293 TI - A new subgenus Wraseellus of the genus Pterostichus Bonelli (Coleoptera, Carabidae, Pterostichini) and new species descriptions. AB - A new subgenus Wraseiellus new subgenus (type species: Pterostichus andrewesi Jedlicka 1931) of the genus Pterostichus from China is described. Eight species and one subspecies are recognized in the new subgenus including three new species and one new subspecies: Pt. (Wraseiellus) comatus new species (Guangxi: Maoershan, N25.87 degrees , E110.42 degrees ), Pt. (Wraseiellus) crassiapex new species (Hubei: Tiechanghuang, N30.75 degrees , E110.30 degrees ), Pt. (Wraseiellus) pseduodiversus new species (Yunnan: Luguhu, N27.63 degrees , E100.82 degrees ), Pt. (Wraseiellus) stictopleurus cangshanensis new subspecies (Yunnan: Cangshan, N25.63 degrees , E100.14 degrees ). Feronia crebrepunctata Straneo, 1937 is newly proposed as junior synonym of Pterostichus meyeri Jedlicka, 1934. A key to all known species and subspecies, images of habitus and genitalia, and distribution maps are provided. PMID- 26266294 TI - Systematics of the weevil genus Mecinus Germar, 1821 (Coleoptera: Curculionidae). II. Phylogenetic analysis based on adult morphological characters and host plant information. AB - A phylogenetic analysis of all species belonging to the weevil genus Mecinus Germar, 1821 (Coleoptera: Curculionidae: Curculioninae: Mecinini) was carried out. Mecinus are exclusively Palaearctic and feed on Plantaginaceae belonging to the tribes Plantagineae and Antirrhineae. Based on a cladistic analysis of six outgroup and 47 ingroup taxa, and 31 adult morphological and three ecological characters, the monophyly of Mecinus appears strongly supported. In this genus six species groups and one monobasic group were recognized. Many species are morphologically similar to one another and lack phylogenetically useable apomorphies; thus for practical convenience these species, which produce highly polytomic topologies, have been treated as the M. pascuorum and the M. elongatus complexes. However, a large assemblage of species, characterized by elongate body shape, appears well supported. This includes the M. collaris, M. circulatus, M. heydenii and M. janthinus groups together with the M. simus group where a reversal to the primitive oval body shape in some species is presumed. Other well supported groups are the M. paratychioides and M. marina groups that appear more related to species of the M. pascuorum complex than to the main clade of elongate species. Optimizing host plant preferences onto the morphological phylogeny indicates that feeding on Plantagineae was the plesiomorphic condition for the genus Mecinus. All species feeding on Antirrhineae, which represent a minority, are included in two well supported groups, tht M. heydenii and M. janthinus groups, which however do not share unequivocal morphological synapomorphies. In general there are no strict relationships between groups of weevils and their specific feeding habits, since larvae of closely related species adopt different strategies, such as seed predators, stem borers or gall inducers. Similarly no distinct biogeographic pattern of Mecinus has been observed in light of the phylogeny. PMID- 26266295 TI - Chirostylidae of Australia's western continental margin (Crustacea : Decapoda: Anomura), with the description of five new species. AB - Five new species from the squat lobster family Chirostylidae are described from the continental margin of western Australia: Uroptychus albus sp. nov., Uroptychus bardi sp. nov., Uroptychus jawi sp. nov., Uroptychus taylorae sp. nov., and Uroptychus worrorra sp. nov. New records of Indo-West Pacific species for Australia are: Gastroptychus brachyterus Baba, 2005, Gastroptychus investigatoris Alcock, 1899, Uroptychodes grandirostris (Yokoya, 1933), Uroptychodes inortenseni (Van Dam, 1939), Uroptychus scandens Benedict, 1902, Uroptychus ciliatus (Van Dam, 1933) and Uroptychus vandamae Baba, 1988. New distributional records are given for species previously recorded from Australia: Uroptychus flindersi Ahyong & Poore, 2004, Uroptychus hesperius Ahyong & Poore, 2004, Uroptychusjoloensis Van Dam, 1939, Uroptychus nigricapillis Alcock, 1901, and Uroptychus spinirostris (Ahyong & Poore, 2004). These new records expand the number of chirostylid species in Australia from 34 to 46. Keys to Australian species of the genera Gastroptychus, Uroptychodes and Uroptychus are provided. PMID- 26266296 TI - Review of the genus Loxocephala Schaum, 1850 (Hemiptera: Fulgoromorpha: Eurybrachidae) with aescription of three new species from China. AB - The genus Loxocephala Schaum, 1850 is reviewed. Three new species: L. rugosa sp. nov., L. verticalis sp. nov. and L. mangkangensis sp. nov. are described from China. L., perpunctata Jacobi, 1944 and L. sinica Chou & Huang, 1985 are given supplementary descriptions. In addition, according to the male genitalia, L. sinica sichuanensis Chou & Huang, 1985 is upgraded to species level: L. sichuanensis Chou & Huang, 1985 stat. nov. A key to all the known species of the genus is provided. PMID- 26266297 TI - A taxonomical review of the Gnathophausia (Crustacea, Lophogastrida), with new records from the northern mid-Atlantic ridge. AB - Taxonomy of 11 species contained within the Lophogastrida genus Gnathophausia is presented. We report new records of G. affinis, G. gigas, G. ingens, and G. zoea from the Atlantic Ocean between Iceland and the Azores. We also describe a new species, G. bergstadi that resembles G. zoea, but differs in having a heart shaped apex on the telson and having the lower later keels of the carapace not fusing with the upper lateral keels. Gnathophausia is found to be most abundant at bathyal depths. G. zoea, G. gigas, and G. ingens are reported distributed throughout the world's oceans. G. affinis and G. bergstadi are confined to Atlantic water masses, whereas G. childressi, G. longispina, and G. elegans, are found in the Pacific. A more limited distribution in tropical regions of the world's oceans is observed in G gracilis, and also G. fagei and G. scapularis that are confined to the South China Sea and Indian Ocean, respectively. We include an identification key and known distribution of all accepted Gnathophausia species. PMID- 26266298 TI - Two new species of genus Apsilochorema Ulmer (Trichoptera: Hydrobiosidae) from India. AB - Two new species of Apsilochorema (Trichoptera: Hydrobiosidae) from India are described, Apsilochorema (Archichorema) kashnirensis sp. nov. and Apsilochorema (Archichorema) meyi sp. nov., bringing to 12 the number of species in the genus known from the country. PMID- 26266299 TI - Revision of the European species of Calotelea Westwood (Hymenoptera: Platygastroidea). AB - The European species of Calotelea are reviewed: previously known species are redescribed; two new species are described: Calotelea carbonaria n. sp. and Calotelea laminata n. sp.; and a key to all species is given. Calotelea affinis Kozlov & Kononova is a junior synonym of Calotelea elegans (Masi) syn. nov. and Calotelea ruficollis (Szelenyi) is transferred to Calliscelio comb. nov. Calotelea laminata n. sp. is the first species of Calotelea belonging to the ocularis group to be recorded from Europe. A morphometric analysis is made of the metasoma of females of all European species of Calotelea. PMID- 26266300 TI - A new species of Pseudoleptochelia Lang, 1973 (Crustacea: Peracarida: Tanaidacea: Leptocheliidae) from the Northwest Atlantic with observations on the status of the genus. AB - Pseudoleptocheliajuliae n. sp. is described from Puerto Rican waters in depths from 1 to 28 m. The new species and P. fairgo from western Australia are the only members of the genus as defined in this revision that have a distinct process on the posterior margin of the cheliped carpus. The male of P. juliae is distinguished from that of P. fairgo by this process being sub-acute and having a distinctly narrower propodus. Lang's generic diagnosis for the female of Pseudoleptochelia is incorrect, which has led to confusion. Based in examination of Mediterranean specimens attributed to the type species P. anomala (Sars), Pseudoleptochelia is rediagnosed to contain seven species; P. anomala; P. fairgo; . juliae; P. magna; P. mortenseni; P. occiporta; and P. straddi., The genus is reviewed and discussed and the taxonomic status for the remaining nine species previously assigned to the genus is re-evaluated. Pseudoleptochelia shares similarities with the more recently described Pacific genera Konarus and Parakonarus and to a lesser extent to the highly derived genus Makraleptochelia. PMID- 26266301 TI - Three new species of Collembola from soils of Mediterranean cork-oak forests of Sicily (Italy). AB - Three new species of soil Collembola from cork-oak (Quercus suber) forests located in eastern Sicily (Italy) are described Neonaphorura alicatai sp. nov., Friesea guarinoi sp. nov. and Arrhopalites antonioi sp. nov.. PMID- 26266302 TI - Two new species of Cardiodectes Wilson, 1917 (Copepoda: Siphonostomatoida: Pennellidae) from gobiid fishes (Actinopterygii: Perciformes) in the western Pacific Ocean. AB - Two new species of the genus Cardiodectes Wilson, 1917 (Siphonostonatoida: Pennellidae) are described based on females from gobiid fishes (Actinopterygii: Perciformes) in coastal waters of the Pacific Ocean. Both new species belong to the 'rubosus' group sharing a trunk without an abdomen. Cardiodectes bellwoodi n. sp. parasitizes Istigobius nigroocellatus (Gunther) in Australian waters and differs from members of the 'rubosus' group by having a trunk length less than twice its width, and a pair of large anterior lobes with branched processes. Cardiodectes shini n. sp. is similar to C. asper Uyeno & Nagasawa but is distinguishable by the presence of a well-developed, bilobed process between the bases of the maxillae, and by the cephalothorax bearing only two pairs of lobes. PMID- 26266303 TI - Review of the systematic status of Sceloporus arenicolus Degenhardt and Jones, 1972 with an estimate of divergence time. AB - The sagebrush lizards (Sceloporus graciosus group) consist of four taxa (S. graciosus graciosus, S. graciosus gracilis, S. graciosus vandenburgianus, and S. arenicolus) distributed in western North America. Of these, S. arenicolus is morphologically, behaviorally, and ecologically distinct as well as geographically disjunct from the other taxa, occurring only in the Mescalero Monahans Sandhills of southeastern New Mexico and adjacent Texas. Sceloporus arenicolus is a taxon of concern because of its small range and habitat alteration due to land use practices. Understanding evolutionary relationships among members of the S. graciosus group, and especially S. arenicolus, has important implications for conservation. We examine the phylogenetic relationship of S. arenicolus relative to the three recognized subspecies of S. graciosus at mitochondrial and nuclear loci for populations sampled throughout the ranges of these taxa. Additionally, we estimate the divergence time and clade age of S. arenicolus. We find that the S. graciosus group is in need of major taxonomic revision, and also confirm that S. arenicolus is a genetically distinct and divergent lineage. These results bear important consequences for conservation and management. PMID- 26266304 TI - New water mite species of the genus Piona Koch, 1842 (Acari, Hydrachnidia: Pionidae) from Northeastern Russia. AB - Descriptions of two new water mite species, Piona inagadanensis (male, female, deutonymph), Piona anadyrensis (male, female, deutonymph) and one new subspecies P interrupta interruptella (female) from standing waters of the Magadan Province and Chukotka of Russia are presented. PMID- 26266305 TI - New species and taxonomic rearrangements of Anostostomatid Crickets (Orthoptera: Stenopelmatoidea: Anostostomatidae) from the Neotropics. AB - This paper describes and illustrates a new species of the genus Anabropsis (Anostostomatidae: Anabropsinae) from Colombia, we group the species of this genus were grouped into three groups: Mexicana, Alata and Aptera. A brief review of the genus Apotetainenus (Anostostomatidae: Lutosinae) is also given including a new species from the Colombian rainforest; also A. clipeatus is redescribed and a new distribution data are provided. Finally A. politus (Brunner, 1915) is designated as synonym of A. clipeatus. PMID- 26266306 TI - Eriophyoid mites (Acari: Prostigmata: Eriophyidae) associated with Compositae in Iran. AB - Five species of eriophyoid mites were identified during surveys of mite fauna associated with plant species of the family Compositae from Southwest of East Azerbaijan province during 2010 and 2011. Two of them, Aceria virgatae n. sp. from Centaurea virgata Lam. and Aceria xeranthenzis n. sp. from Xeranthemumn squarrosum Boiss., were found to be new to science. No damage symptoms were observed on their host plants. Aceria xeranthemis n. sp. is the first eriophyoid collected from the plant genus Xeranthenun. Aculops centaureae (Farkas, 1960) from Centaurea albonitens Turrill and Aceria cichorii Petanovic et al. 2000 from Cichorium intybus L. are new records for Iranian mite fauna. The deutogyne female of Aceria anthocoptes (Nalepa) was recorded for the first time in Iran, too. A key to the species collected on Compositae in Iran is given. PMID- 26266307 TI - A new miniature species of Characidium Reinhardt (Ostariophysi: Characiformes: Crenuchidae) from the headwaters of the rio Araguaia, Brazil. AB - Characidium inirim is described from the rio das Mortes, rio Araguaia basin in Central Brazil. The new species is distinguished from its congeners by having an incomplete lateral line, a conspicuous dark longitudinal stripe and dark transverse bars not extending ventrally to the lateral line, and by lacking the adipose fin and the dark caudal blotch. A phylogenetic hypothesis based on the available data on the phylogenetic relationships of the subfamily Characidiinae is presented. Results suggest that the new species is closely related to C. bahiensis, C. interruptum, C. lagosantense, C. nupelia, C. lanei, C. laterale, C. occidentale, C. orientale, C. rachovii, C. stigmosun, C. vestigipinne and C. xavante. PMID- 26266308 TI - New species of Pyrrhulina (Ostariophysi: Characiformes: Lebiasinidae) from the Brazilian Shield, with comments on a putative monophyletic group of species in the genus. AB - Pyrrhulina marilynae, new species, is described. The new species can be distinguished among congeners mainly by presenting a conspicuous, dark, zigzag shaped primary stripe, extending to distal end of median caudal-fin rays, reduction of the number of precaudal vertebrae, absence of postecleithrum 2, and nine principal rays on caudal-fin dorsal lobe. The putative relationship of the new species with Pyrrhulina australis, P. vittata and P. zigzag, three small sized species of the genus, is discussed. PMID- 26266309 TI - The genus Hecabolus Curtis 1834 (Braconidae: Doryctinae) in South America, with description of six new species. AB - Six new species of the doryctinae wasp genus Hecabolus Curtis 1834 (Braconidae) are described from Brazil and Venezuela: H. assis sp. nov., H. julianoi sp. nov., H. robustus sp. nov., H. seniaridus sp. nov., H. shimborii sp. nov., and H. sulmatogrossensis sp. nov. A key to the nine described species of Hecabolus is provided. PMID- 26266310 TI - Two new species of Glossosoma subgenus Glossosoma (Trichoptera: Glossosomatidae) from India. AB - Two new species of the genus Glossosoma (Glossosoma) Curtis are described and illustrated: G. (G.) dirangense sp. nov, and G. (G.) sikkimnense sp. nov. from Dirang (Arunachal Pradesh) and Lachen (Sikkim), respectively. Glossosoma (G.) dirangense most closely resembles G. (G.) mnoselyi Kimmins 1953, but the males of these species can be distinguished by differences in the shapes of abdominal segments IX and X. Glossosoma (G.) sikkimense most closely resembles G. (G.) fissumn Martynov 1935 and G. (G.) caudatum Martynov 1931, but the male of G. (G.) sikkimense can be distinguished from these other species by differences in the shapes of abdominal segment X, sternite VI ventral process, and the phallus. PMID- 26266311 TI - Two new species of caddisflies (Trichoptera: Hydroptilidae, Psychomyiidae) from central and south Spain. PMID- 26266312 TI - Revision of Breda and proposal of a new genus (Araneae: Salticidae). AB - The genus Breda Peckham & Peckham, 1894 is revised and nine valid species are redescribed and illustrated. The monotypic Paradescanso Vellard, 1924 is established as a new junior synonym of the genus. Breda modesta (Taczanowski, 1878) comb. nov. is transferred from Balmaceda Peckham & Peckham. The following synonymies are also established: Paradescansofallax Vellard, 1924 = Breda apicalis Simon, 1901 syn. nov.; B. quinquedentata Badcock, 1932 = B. apicalis Simon, 1901 syn. nov.; B. leucoprocta Mello-Leitao, 1940 = B. modesta (Taczanowski, 1878) syn. nov.; B. spinimanu (Mello-Leitao, 1941) = B. modesta (Taczanowski, 1878) syn. nov. The females of B. bicruciata (Mello-Leitao, 1943) and B. bistriata (C.L. Koch, 1846) are described and illustrated for the first time, as well as the male of B. lubomirskii (Taczanowski, 1878). Both sexes of Breda akypueruna sp. nov. and males of B. nanica sp. nov. and B. paraensis sp. nov., all three from the Amazon, are described and illustrated, increasing the present member list up to 13 species. Druzia gen. nov. is proposed to include B.flavostriata Simon, 1901. The Australian "Breda" jovialis (L. Koch, 1879) is tentatively transferred to Ocrisiona Simon. PMID- 26266313 TI - Morphology and molecular phylogeny of Macrobrachium snpurii, a new species of the genus Macrobrachium Bate, 1868 from Kerala, India. AB - Macrobrachium snpurii sp. nov., collected from the Karamana River, in the lower reaches of Western Ghats, is described and illustrated. DNA barcoding using Cytochrome B gene sequences has elucidated the taxonomic status of the new species and the NJ tree reveals that M. snpurii sp. nov., is phylogenetically close to M. idella idella. However, morphometric and meristic features of the species share certain characters with M. idella idella, M. patheinense and M. tratense, while it diverges remarkably from these three species in distinctive diagnostic characters: rostral formula 12-14/4 with 2 postorbital teeth; carapace smooth with distal end of rostrum directed upwards; chelae with 2 proximal denticles both in the movable and immovable fingers. A wide gap present in the distal part of the chelae, when fingers are closed. Movable finger, longer than the immovable and distal end of fingers inwardly hook-like; palm more pigmented than fingers and telson extends beyond the level of the outer lateral spine of uropodal exopod. A pair of plumose setae is present between the inner pair of movable spines of telson. PMID- 26266314 TI - Review of the marine isopod crustacean genus Hansenium Serov and Wilson, 1995 (Asellota: Stenetriidae) from tropical Australia and Papua New Guinea, with description of a new genus. AB - The genus Hansenium is revised and a new diagnosis presented. A neotype is designated for the type species Hansenium hanseni (Muller, 1991), and the genus is restricted to the type species and Hansenium remocarpus Kensley and Schotte, 2002. Machatrium gen. nov. and the following species are described: Machatrium falcensis sp. nov. (type species), Machatrium thungku sp. nov. from Lizard Island, Great Barrier Reef; Machatrium wongat sp. nov. from Madang, Papua New Guinea, Machatrium tropex (Bolstad and Kensley, 1999), comb. nov. also from Madang, Papua New Guinea; a further five species are transferred from Hansenium to Machatrium gen. nov. The remaining species of Hansenium are retained as incertae sedis in their existing combination (11 species), reallocated to other genera (1 species) or regarded as species inquirenda (3 species). The principal differentiating characters of Hansenium, Machatrium gen. nov. and Stene triumn Haswell, 1881, are the pseudorostrum being short and trapezoid or long and anteriorly narrowed, morphology of the male pereopod 1, notably the shape of the propodus inferior margin, presence or absence of a process on the inferodistal margin of the merus and carpus; and the apex of the appendix masculina being acute or blunt, with or without a concavity and with or without terminal setae. PMID- 26266315 TI - Revision of the Japanese Ablabesmyia (Diptera: Chironomidae: Tanypodinae), with descriptions of three new species. AB - The Japanese species of Ablabesmyia Johannsen are reviewed on the basis of the type material and the specimens obtained recently. Four species of the subgenus Ablabesmyia, A. (A.) monilis (Linnaeus), A. (A.) amamisimplex Sasa, A. (A.)jogancornua Sasa et Okazawa and A. (A.) prorasha Kobayashi et Kubota, are recognized as valid. The adults, male and female, and the immature stages, pupa and larva, of the first species and the adult males of the remaining are redescribed, while the female adults and both immature stages of A. (A.) amamisimplex and A. (A.) jogancornua, and both immature stages of A. (A.) prorasha are described here for the first time. Reexamination of the holotypes of A. (A.) amamisimplex and A. (A.) jogancornua has shown that the respective original descriptions contain errors in some diagnostic aspects, which are corrected in this study. In addition, the male and female adults, pupa and larva of a new species of the subgenus Karelia Roback, A. (K.) nakarchenkoi n. sp., and the male adults of two new species, A. (K.) lata n. sp. and A. (K.) perexilis n. sp., are described and illustrated. PMID- 26266316 TI - Cryptic speciation within Asthenodipsas vertebralis (Boulenger, 1900) (Squamata: Pareatidae), the description of a new species from Peninsular Malaysia, and the resurrection of A. tropidonotus (Lidth de Jude, 1923) from Sumatra: an integrative taxonomic analysis. AB - A review of the taxonomic status of the Asian Slug Snake, Asthenodipsas vertebralis (Boulenger, 1900) based on an integrative taxonomic approach using molecular, morphological, color pattern, and ecological data indicate it is composed of three well supported monophyletic lineages: (1) Pulau Tioman and Fraser's Hill, Pahang and Bukit Larut, Perak; Peninsular Malaysia; (2) its sister lineage from Northern Sumatra; and (3) the remaining basal lineage from Peninsular Malaysia. Furthermore, we consider the high sequence divergence (6.3% 10.2%) between these lineages (especially in areas of sympatry) and discrete differences in their morphology, color pattern, and microhabitat preference as evidence they are not conspecific. As such, we resurrect the name A. tropidonotus (Lidth de Jeude, 1923) for the Sumatra populations, restrict the name A. vertebralis to the populations from Pulau Tioman, Genting Highlands, Fraser's Hill, Gunung Benom, and Bukit Larut that contain terrestrial, banded adults; and consider A. lasgalenensis sp. nov. to be restricted to the populations from Fraser's Hill, Cameron Highlands, and Bukit Larut that contain arboreal, unbanded adults. PMID- 26266317 TI - Description and host interactions of a new species of Exetasis Walker (Diptera: Acroceridae), with a key to species of the genus. AB - Exetasis jujuyensis Gillung sp. nov. (Acroceridae) is described from Argentina and a dichotomous key to species of Exetasis Walker is provided. Detailed observations are presented on the effect of fly larval development on the behavior of the host spider (Acanthoscurria sternalis Pocock (Theraphosidae)). PMID- 26266318 TI - Two new subspecies of the leaf-tailed gecko Phyllurus ossa (Lacertilia: Carphodactylidae) from mid-eastern Queensland, Australia. AB - Following the discovery of a new population of Phyllurus ossa on Whitsunday Island in the Cumberland Island Group, eastern Queensland, we conducted both genetic and morphological analyses to assess differences between all known populations. The analyses revealed three genetically distinct, morphologically diagnosable, geographical units. The differences are such that we recognise these as subspecies: Phyllurus ossa ossa restricted to the Mt Ossa/Mt Pelion/ Mt Charlton/ St Helens Gap area; P. ossa hobsoni subsp. nov. on Mt Dryander and in the Conway Range and P. ossa tamoya subsp. nov. currently only known from Whitsunday Island. There are now 11 recognised taxa in Phyllurus. The three P. ossa subspecies are narrowly distributed and closely associated with exposed rock in low to mid-elevation vine forests. Their current distributions are shaped by past climate change that progressively contracted and fragmented the distribution of rainforests in eastern Australia. The recognition of these subspecies has land management/conservation implications. PMID- 26266319 TI - Three new species of Caridina (Decapoda: Atyidae) from Central Sulawesi and Buton Island, Indonesia, and a checklist of the islands' endemic species. AB - Three atyid shrimp species of the genus Caridina Milne Edwards, 1837, Caridina boehmei n. sp., C. laroeha and C. butonensis n. sp., are described from the Indonesian islands Sulawesi and Buton. Caridina boehinei n. sp. differs from its apparently next congener C. sulawesi Cai & Ng, 2009 by the shape of the spinulation of the male sexual appendages. Caridina laroeha resembles C. mahalona and C. opaensis, but can be distinguished by the length and armature of the rostrum, the length ratio of segments of the third maxilliped and the number of spinules on the uropodal diaeresis. Caridina butonensis n. sp. resembles to C. boehmei n. sp. and C. opaensis but can be distinguished by its peculiar truncated rostrum and by a more reduced podobranch on the second maxilliped. PMID- 26266320 TI - Madeira's ptyctimous mites (Acari, Oribatida). AB - In the material recently collected in Madeira, 16 species of ptyctimous mites have been found. A new species of Austrophthiracarus rabacalensis Niedbala sp. nov. has been described. The presence of P. globosus and S. (R.) ortizi, reported earlier from Madeira has not been confirmed, but P. anonymus and P. montanus, so far not reported from this island, have been found. All 16 species identified in the material from Madeira studied occur in the Palaearctic Region; four of them are endemites, seven occur in western Palaearctic, four are panpalaearctic, while one is a semicosmopolitan. Morphological analysis has revealed a high similarity of two endemic species of Madeira with two European species: Steganacarus (Steganacarus) crassisetosus is similar to Steganacarus (Steganacarus) applicatus, while Steganacarus (Steganacarus) similis to Steganacarus (Steganacarus) spinosus. DNA-barcode analysis using COI and D2 28S rDNA sequences confirmed the species status of these four species. The phylogenetic analyses of COI amino acid data and D2 28S rDNA sequences suggest a closer relationship between S. (S.) crassisetosus and S. (S.) applicatus, pointing to a great genetic distance between S. (S.) spinosus and the other species of Steganacarus (Steganacarus). PMID- 26266321 TI - Nine new species of Soesilarishius from Brazil (Araneae: Salticidae: Euophryinae). AB - Nine new species of Soesilarishius Makhan, 2007 are described from Brazil, raising the genus member list up to 20 species. Soesilarishius chaplini sp. nov., S. paxiuba sp. nov. and S. muiratinga sp. nov. are described from the state of Para. Soesilarishius bicrescens sp. nov., S. excentricus sp. nov. and S. flagellator sp. nov. are described from the state of Piaui. Soesilarishius inacrochelis sp. nov. and S. cearensis sp. nov. are described from the state of Ceara. Soesilarishius tabernarius sp. nov. is described from the state of Bahia. Both sexes are described for the new species, except for S. inuiratinga, S. bicrescens, S. excentricus and S. tabernarius, whose females remain unknown. PMID- 26266322 TI - [Establishment of malaria early warning system in Jiangsu Province IV Implementation of key measures to eliminate malaria in Jiangsu Province in 2013]. AB - OBJECTIVE: To promote the malaria control process in the malaria elimination stage in Jiangsu Province. METHODS: The data from the network reporting system of medical institutions, the disease prevention and control institutions at all levels, and the special reports system of parasitic diseases were collected and analyzed statistically. RESULTS: There were 341 malaria cases directly reported from the Jiangsu provincial network in 2013. All were laboratory-confirmed cases. Except one case of blood transfusion infection, the rest were imported malaria cases abroad. All the malaria cases were reported after diagnosis within 24 hours through the directly reported network, and the implementation rate was 100%. All the malaria cases had an epidemiological investigation within 3 days with the implementation rate of 100%; in which 334 (97.95%) cases were investigated within 2 days. All the cases had an epidemical investigation and disposition within 7 days with the implementation rate of 100%, in which 319 cases (93.55%) were completed within 5 days. CONCLUSIONS: The implementation rate of malaria elimination work mode has reached 100% in Jiangsu Province in 2013, and there are no local infected malaria cases for two consecutive years. However, the inspection and supervision of case investigation and epidemic investigation and disposal are still need to he strengthened. PMID- 26266323 TI - Substrate effects on the monovacancies of silicene: studied from first principle methods. AB - The geometrical structures and electronic properties of defective silicene with monovacancies (MVs), placed on two different substrates, a h-BN sheet and an Ag(111) surface, have been investigated using the first-principles method. It is found that due to the weak van der Waals interaction from the h-BN sheet, there exists two kinds of MVs in the Si|h-BN composite, i.e., the self-healing MV-1 and MV-2 with a closed five- and nine-membered (5-9) pair of rings, with the former as the ground state MV, which is the same as in the case of the free-standing silicene with MVs. The electronic bands around the Fermi level of the Si|h-BN composite with the Si MVs are all induced by the Si atoms, leading to a nonmagnetically metallic ground state. But the Ag(111) substrate has a stronger coupling with the Si adlayer, leading to the existence of three kinds of inequivalent Si atoms, greatly changing the MV structures and the stability of the defective silicene adlayer, as well as its corresponding electronic structures. For example, the symmetric-like MVs are found to always be the stable MV structures in the Si|Ag(111) composite, no matter which type of inequivalent Si atom is removed from it. The Ag substrate has a dominant contribution to the electronic bands of the defective Si|Ag(111) composite with the Si MVs. Even so, some characteristic bands induced by the Si MV defects could still be found. PMID- 26266324 TI - Sarcopenia impairs survival in patients with potentially curable hepatocellular carcinoma. AB - BACKGROUND: A reduction in skeletal muscle mass (sarcopenia) independently predicts poor survival in patients with hepatocellular carcinoma (HCC) undergoing treatment with curative intent. Whether this is due to an increased risk of recurrence and disease specific death, or due to an increased risk of postoperative morbidity and mortality is currently unclear. In this study, we investigate the association between sarcopenia and death in a cohort of HCC patients undergoing treatment with curative intent. METHODS: Patients undergoing surgical resection or radiofrequency ablation for lesions <= 3 cm between 2002 and 2013 were identified. Clinicopathological characteristics, CT-assessed sarcopenia and outcomes were analyzed. RESULTS: Among 90 patients, 52 (57.8%) were found to be sarcopenic. Sarcopenic patients had a limited overall survival (median: 33 months vs. non-sarcopenic median: 105 months; P = 0.002), but not disease-free survival. Sarcopenia was an independent predictor for overall survival in multivariate Cox-regression analysis (HR 3.756; P = 0.001). Major complications (32.7% vs. 13.2%, P = 0.033) and treatment-related mortality (17.3% vs. 2.6%, P = 0.029) were more frequent in sarcopenic patients. CONCLUSION: Sarcopenia impairs survival in patients with potentially curable hepatocellular carcinoma, mainly due to an increase in treatment-related mortality. PMID- 26266325 TI - Construction of tissue microarrays from core needle biopsies - a systematic literature review. AB - In some clinical circumstances, core needle biopsy (CNB) may be the only source of material from cancer tissue for diagnostic use. The volume of tissue available in a CNB is low, and opportunities for research use can therefore be limited. The tissue microarray (TMA) principle, if applied to the use of CNBs, could facilitate research studies in circumstances where CNB specimens are available. However, various challenges are expected in applying such a technique in CNBs, which has limited their use in research. We therefore conducted a systematic review of the literature on this subject. A systematic search was carried out with CINAHL, EMBASE, the Cochrane library, and MEDLINE, to identify studies that have primarily developed methods for constructing TMAs from CNBs. Eight studies were found to meet the inclusion criteria; six of these employed the vertical rearrangement technique, and two used multiple layers of biopsy tissue. Representation of the CNB was significantly influenced by the quantity of tumour cells present in the original biopsy and the degree of heterogeneity of biomarker expression. This review shows that technologies have been developed to enable construction of TMAs from CNBs. However, challenges remain to improve amplification and representation. PMID- 26266326 TI - Fine-Tuning of Magnetic Properties in Nickel(II) Trinuclear EMACs via Modifications of Equatorial Ligands. AB - The relationship between equatorial ligands structures and magnetic response of [Ni3]6+ extended metal atom chain core has been investigated. The distances between metal ions in Ni metal strings are largely predefined by framework provided through equatorial ligands. The equatorial ligands thus have primary influence on the magnitude of magnetic coupling between terminal high spin centers. Since the sigma channel has greatest contribution to J, the variations in Ni-Ni bond lengths have immediate and strong effect on magnetic properties. The secondary, yet important role is played by ligand field strength and nucleophilicity. It has been shown that energy difference between singly occupied sigma-type MOs composed of d(z2) of terminal ions and doubly occupied sigma-type MO evolved from d(z2) of the central ion in antiferromagnetic state solution is inversely proportional to magnitude of J. Hence, the alignment between energies of d(z2) orbitals on HS and LS centers directly affected by ligand field strength governs the magnetic response. Moreover, the greater basicity of lone pairs coordinating terminal metal atoms correlates with the larger absolute value of magnetic coupling constant. PMID- 26266327 TI - Troponin T and NT ProBNP Levels in Gestational, Type 1 and Type 2 Diabetic Mothers and Macrosomic Infants. AB - This study compares NT proBNP and troponin T levels in umbilical cord arterial blood and postnatal echocardiographic findings for infants of gestational and pregestational diabetic mothers and macrosomic infants. Twenty-seven infants of pregestational diabetic mothers, 61 infants of gestational diabetic mothers and 37 macrosomic infants of nondiabetic mothers were prospectively enrolled in this study along with a control group of 58 healthy infants of mothers without any pregestational or gestational disorders as the control group. All enrollees were born after 34 weeks of gestation. For this study, umbilical cord blood was drawn during delivery to determine NT proBNP and troponin T levels. Echocardiography was performed 24-72 h after the delivery. Umbilical cord troponin T and NT proBNP levels were found to be higher in the diabetic and macrosomic groups than in the control group (all of them p < 0.001). NT proBNP levels were positively correlated with interventricular septum thickness in the pregestational and gestational infants of diabetic mothers groups (r = 0.564 and r = 0.560, respectively, p < 0.01). Both pregestational and gestational diabetic mothers were divided into two groups according to HbA1c levels in the third trimester as good (<6.1 %) and suboptimal (>6.1 %) metabolic control. In the good and suboptimal metabolic control diabetic groups, NT proBNP levels were also positively correlated with interventricular septum thickness (r = 0.536 and r = 0.576, respectively, p < 0.01). In the suboptimal metabolic control diabetic group, NT proBNP was only found to be positively correlated with the left ventricular mass index (r = 0.586, p < 0.01). While there was no correlation in the myocardial performance index between infants of diabetic mothers and the control group, the myocardial performance index of macrosomic infants was lower than that of the control group (p = 0.017). Cardiac biomarkers (NT proBNP and troponin T) were elevated in infants of diabetic mothers and macrosomic infants. While there was a positive correlation between NT proBNP levels and cardiac structure in infants of pregestational and gestational diabetic mothers, there was no relationship between NT proBNP levels and cardiac function. PMID- 26266328 TI - Progression of Aortic Regurgitation After Different Repair Techniques for Congenital Aortic Valve Stenosis. AB - We sought to characterize the incidence of AR progression and determine risk factors for AR progression in a consecutive series of infants and children after surgical correction of congenital aortic valvular and supravalvular stenosis. N = 30 patients underwent repair of the aortic valve for isolated congenital aortic valve stenosis (n = 14, 47 %) or combined with aortic regurgitation (AR, n = 16, 53%). N = 27 (90%) had a valvular and n = 3 patients (10%) presented with supravalvular pathology of their aortic valve. In n = 16 patients (53%) a bicuspid and in n = 2 (6%) patients, a unicuspid valve was present. Comparative survival was analyzed using the Cox model and log-rank calculations. Log-rank calculations were performed for variables reaching statistical significance in order to identify differences in survival between groups. Commissurotomy was performed in n = 20 patients, patch implantation in n = 4, cusp shaving in n = 8, cusp prolapse correction in n = 3, and cusp augmentation in n = 4 patients. In patients with combined dysfunction and preoperative AR, AR was successfully reduced by the initial procedure, and postoperatively the overall median AR grade was 1+ (range 0-2.5+, p = 0.001, for AR reduction among patients with any grade of preoperative AR). By the time of follow-up echocardiography, the median AR grade had significantly progressed toward 1.5+ (p = 0.004). At the time of mid term follow-up at 3.2 years, none of the patients had moderate or severe AR grades >2.5+. Patients with a monocuspid aortic valve and patients who had some kind of patch implantation into their cusps or commissures or shaving of thickened cusps were more likely to present with progression of aortic regurgitation. Monocuspid aortic valve and patch implantation, as well as cusp shaving, are probably linked to AR progression. The standard procedure of commissurotomy results in an absolute rate of AR progression of 40 % over a medium-term follow-up period. PMID- 26266329 TI - Consider a Nongenetic Pathogenesis of Noncompaction. PMID- 26266330 TI - Highly Transparent Dual-Sensitized Titanium Dioxide Nanotube Arrays for Spontaneous Solar Water Splitting Tandem Configuration. AB - Vertically aligned one-dimensional (1D) titanium dioxide (TiO2) arrays on transparent conducting oxide (TCO) substrates, which can act as host electron transport materials for low bandgap materials, were synthesized via a hydrothermal reaction combined with a controlled chemical etching process. By controlling the chemical etching conditions, we can maximize the light transmission properties of the 1D TiO2 arrays, which is beneficial for the front electrode in photoelectrochemical (PEC) tandem configurations. As a result, dual sensitization to form 1D TiO2@CdS@CdSe (CdS and CdSe coated 1D TiO2) results in excellent photocurrent density, as well as transparency, and the resulting material is able to pass unabsorbed photons through the front electrode into the rear bias solar cell. Owing to the improved light transmission in combination with the increased specific surface area of the obtained 1D TiO2 arrays from the controlled etching process, a high-efficiency PEC tandem device with ~2.1% was successfully fabricated for unassisted hydrogen evolution. Efficient PEC tandem device was fabricated for unassisted solar hydrogen generation using highly transparent composite electrode composed of dual sensitization to form 1D TiO2@CdS@CdSe. PMID- 26266331 TI - Theoretical spectroscopic studies on chemical and electronic structures of arginylglycine. AB - The energy differences between canonical and zwitterionic isomers of arginylglycine (ArgGly) at the CCSD/aug-cc-pVDZ level are too small (less than 1 kcal mol(-1)) to determine the dominant form in the gas phase from the energetic point of view. First-principles simulations have been performed for near-edge X ray absorption fine-structure (NEXAFS) spectra and X-ray photoelectron spectra (XPS) at C, N and O K-edges, as well as for infrared (IR) spectra of neutral ArgGly. Noticeable spectral differences were found which enable the unambiguous identification of different neutral groups. We thus demonstrate X-ray spectroscopy as a powerful technique to study the conformation dependent chemical and electronic properties of neutral ArgGly. PMID- 26266332 TI - Fluorescence Behaviour and Singlet Oxygen Production of Aluminium Phthalocyanine in the Presence of Upconversion Nanoparticles. AB - NaYF4:Yb/Er/Gd upconversion nanoparticles (UCNP) were synthesised and the photoemission stabilised by embedding them in electrospun fibers. The photophysical behaviour of chloro aluminium tetrasulfo phthalocyanine (ClAlTSPc) was studied in the presence of UCNPs when the two are mixed in solution. The fluorescence quantum yield value of ClAlTSPc decreased in the presence of UCNPs due to the heavy atom effect of UCNPs. This effect also resulted in increase in triplet quantum yields for ClAlTSPc in the presence of UCNPs. The fluorescence lifetimes for UCNPs were shortened at 658 nm in the presence of ClAlTSPc when the former was embedded in fiber and suspended in a dimethyl sulfoxide solution of the latter. A clear singlet oxygen generation by ClAlTSPc though Forster resonance energy transfer was demonstrated using a singlet oxygen quencher, 1,3 diphenylisobenzofuran. PMID- 26266333 TI - Rigid Coumarins: a Complete DFT, TD-DFT and Non Linear Optical Property Study. AB - The electronic structures and photophysical properties of rigid coumarin dyes have been studied by using quantum chemical methods. The ground-state geometries of these dyes were optimized using the Density Functional Theory (DFT) methods. The lowest singlet excited state was optimized using Time -Dependent Density Functional Theory [TD-B3LYP/6-31G(d)]. On the basis of ground- and excited-state geometries, the absorption and emission spectra have been calculated using the DFT and TD-DFT method. All the calculations were carried out in gas phase and in acetonitrile medium. The results show that the absorption maxima and fluorescence emission maxima calculated using the Time-Dependent Density Functional Theory is in good agreement with the available experimental results. To understand the Non- Linear Optical properties of coumarin dyes we computed dipole moment (MU), electronic polarizability (alpha), mean first hyperpolarizability (betao) and second hyperpolarizability (gamma) using B3LYP density functional theory method in conjunction with 6-31G(d) basis set. PMID- 26266334 TI - Adenosine Triphosphate-Triggered Release of Macromolecular and Nanoparticle Loads from Aptamer/DNA-Cross-Linked Microcapsules. AB - The synthesis of stimuli-responsive DNA microcapsules acting as carriers for different payloads, and being dissociated through the formation of aptamer-ligand complexes is described. Specifically, stimuli-responsive anti-adenosine triphosphate (ATP) aptamer-cross-linked DNA-stabilized microcapsules loaded with tetramethylrhodamine-modified dextran (TMR-D), CdSe/ZnS quantum dots (QDs), or microperoxidase-11 (MP-11) are presented. In the presence of ATP as trigger, the microcapsules are dissociated through the formation of aptamer-ATP complexes, resulting in the release of the respective loads. Selective unlocking of the capsules is demonstrated, and CTP, GTP, or TTP do not unlock the pores. The ATP triggered release of MP-11 from the microcapsules enables the MP-11-catalyzed oxidation of Amplex UltraRed by H2O2 to the fluorescent product resorufin. PMID- 26266335 TI - Imaging nano-objects by linear and nonlinear optical absorption microscopies. AB - Absorption based microscopy measurements are emerging as important tools for studying nanomaterials. This review discusses the three most common techniques for performing these experiments: transient absorption microscopy, photothermal heterodyne imaging, and spatial modulation spectroscopy. The focus is on the application of these techniques to imaging and detection, using examples taken from the authors' laboratory. The advantages and disadvantages of the three methods are discussed, with an emphasis on the unique information that can be obtained from these experiments, in comparison to conventional emission or scattering based microscopy experiments. PMID- 26266336 TI - Asymmetry in elite rowers: effect of ergometer design and stroke rate. AB - Between limb movement asymmetries and foot force production asymmetries are thought to be detrimental for both rower's performance and risk of injury, particularly when rowing frequently on ergometers. Several ergometers with different designs can be used by rowers as part of their indoor training. Hence, this study aimed to compare asymmetries in lower limb joint kinematics and foot force production with respect to ergometer design and rowing intensity. A new symmetry index was proposed to assess these asymmetries in elite rowers during a test on three ergometers. Additionally, the asymmetry in lower limb length was assessed to investigate its relationship with kinematic and kinetic asymmetries. Parameters describing medium (5-10%) or high (>10%) asymmetries were compared between rowing ergometers and intensities. Results indicated medium asymmetries for the ankle joint angle and hip-knee joint accelerations and high asymmetries for the resultant force and the ankle joint acceleration associated with a low inter-stroke variability. Kinetic asymmetry was neither correlated to kinematic asymmetry nor with lower limb length asymmetry. The use of a mobile ergometer led to higher joint acceleration asymmetries. Further studies are necessary to investigate the relation between these findings and muscular adaptations that may increase the risk of lower-back injury. PMID- 26266337 TI - High-frequency sensorineural hearing loss in children. AB - OBJECTIVES/HYPOTHESIS: Determine the prevalence of high-frequency sensorineural hearing loss (HFSNHL) in our hearing loss population and a diagnostic algorithm for these patients. STUDY DESIGN: Retrospective case series. METHODS: We identified patients diagnosed with sensorineural hearing loss (SNHL) at our pediatric tertiary care institution from 1981 to 2010. Based on audiometric profiles, these patients were subdivided into those with a flat SNHL configuration and those with HFSNHL. Imaging and genetic testing data and data regarding age at diagnosis, laterality, and risk factors were obtained for both groups. Comparisons were then made between the two groups. RESULTS: Of 2,867 patients included in the study, 7.6% had HFSNHL. Age at diagnosis was significantly higher in HFSNHL patients (8.3 years vs. 6.1 years; P < .0001). These patients also had a significantly higher proportion of unilateral versus bilateral loss (49.1% vs. 26.1%; P < .0001); unilateral losses were also less severe. Genetic testing showed no significant difference between groups in the proportion of patients tested or in those who tested positive. Similarly, imaging data revealed no difference in the proportion of patients tested in the two groups; however, overall diagnostic yield was significantly higher in flat SNHL patients (29.5% vs.17.3; P = .02). CONCLUSIONS: The positive predictive value of simple genetic testing is similar to that of imaging studies. However, given cost differences between genetic testing and imaging, it is prudent to perform genetic testing as the initial diagnostic test. Determination of whether high-throughput, multigene diagnostic platforms offer an added benefit in the evaluation of children requires further study. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1236 1240, 2016. PMID- 26266338 TI - Residential and occupational exposure to pesticides may increase risk for cutaneous melanoma: a case-control study conducted in the south of Brazil. AB - BACKGROUND: Incidences of primary cutaneous melanoma (CM) have risen over the last few decades, mainly among populations of White European extraction. Some risk factors for melanoma have been clearly established, but other potential risk factors, such as exposure to pesticides, are currently under study. METHODS: A case-control study on melanoma was conducted during 2012 and 2013 at three dermatological reference centers in Porto Alegre, Brazil. A total of 191 CM patients and sex- and age-matched control subjects were enrolled in the study. Data on domestic and occupational use of pesticides and the risk factors already established for CM were collected. Multivariate logistic regression was used to study the association between exposure to pesticides and melanoma risk. RESULTS: Subjects exposed to pesticides had twice the level of risk for melanoma (odds ratio [OR] 2.03, 95% confidence interval [CI] 1.03-6.89). When pesticides were used indoors for >10 years, the risk for CM increased further (OR 2.84, 95% CI 1.56-5.33). A high frequency of indoor use of pesticides (four or more times per year) was associated with a 44% increase in the risk for melanoma (OR 1.44, 95% CI 1.11-3.49). The domestic use of pesticides outdoors was not associated with increased risk. Subjects exposed to pesticides at an occupational level were at four times greater risk than subjects who were not occupationally exposed (OR 4.23, 95% CI 1.94-6.31). CONCLUSIONS: These findings indicate that the general use of pesticides, particularly indoor domestic use, frequently and over a long period, may be an independent environmental risk factor for CM. PMID- 26266340 TI - Hydrogen segregation and its roles in structural stability and metallization: silane under pressure. AB - We present results from first-principles calculations on silane (SiH4) under pressure. We find that a three dimensional P-3 structure becomes the most stable phase above 241 GPa. A prominent structural feature, which separates the P-3 structure from previously observed/predicted SiH4 structures, is that a fraction of hydrogen leaves the Si-H bonding environment and forms segregated H2 units. The H2 units are sparsely populated in the system and intercalated with a polymeric Si-H framework. Calculations of enthalpy of formation suggest that the P-3 structure is against the decomposition into Si-H binaries and/or the elemental crystals. Structural stability of the P-3 structure is attributed to the electron-deficient multicenter Si-H-Si interactions when neighboring silicon atoms are linked together through a common hydrogen atom. Within the multicenter bonds, electrons are delocalized and this leads to a metallic state, possibly also a superconducting state, for SiH4. An interesting outcome of the present study is that the enthalpy sum of SiH4 (P-3 structure) and Si (fcc structure) appears to be lower than the enthalpy of disilane (Si2H6) between 200 and 300 GPa (for all previously predicted crystalline forms of Si2H6), which calls for a revisit of the stability of Si2H6 under high pressure. PMID- 26266339 TI - The usefulness of immunotherapy in pediatric neurodegenerative disorders: A systematic review of literature data. AB - Immunotherapeutic strategies to treat neurodegenerative disorders have inspired the scientific community. The aim of our review is to address the translational aspects of neuroimmunology to describe the efficacy of immunotherapy in the treatment of pediatric neurodegenerative disorders. In the studies we analyzed IVIG were found to be efficient in the treatment of post-streptococcal neurodegenerative disorders, even if in PANDAS, plasma-exchange (PE) showed a higher efficiency. IVIG were also successfully used in ADEM and Guillan-Barre syndrome. In Sydenham Chorea the use of methylprednisolone was found in most cases as efficient as IVIG, while in Tourette's Syndrome, Colecoxib was successfully used in one patient. Pediatric Multiple Sclerosis seems to respond better to immunosuppressant agents (Mitoxantrone, Cyclophosphamide, Natalizumab), as well as Neuromyelitis optica (Rituximab, Mycofenolate). The importance of this review relies in the attempt to draw standardized guidelines for immunotherapy in pediatric neurodegeneratve disorders. PMID- 26266341 TI - Expression profile of critical genes involved in FGF signaling pathway in the developing human primary dentition. AB - Mammalian tooth development is regulated by paracrine signal molecules of several conserved family interactions between epithelium and mesenchyme. The expression patterns and regulative roles of FGF signaling have been extensively studied in the mouse odontogenesis; however, that is not well known in human tooth development. In order to unveil the molecular mechanisms that regulate human tooth morphogenesis, we examined the expression patterns of the critical molecules involved in FGF signaling pathway in the developing human tooth germ by in situ hybridization, immunohistochemistry, and real-time RT-PCR, including FGF ligands, receptors, and intracellular transducer. We found overlapping but distinct expression pattern of FGF ligands and receptors in the different stages and components. Expression of FGF4, FGF7, FGF8, and FGF9 persists widespread in human tooth mesenchyme, which is quite different to that of in mouse. FGFR1 may be the major receptor in regulate mechanisms of FGF signals in human tooth development. Real-time RT-PCR indeed confirmed the results of in situ hybridization. Results of K-Ras, p-ERK1/2, p-p38, p-JNK, and p-PDK1 expression reveal spatial and temporal patterns of FGF signaling during morphogenesis and organogenesis of human tooth germ. Activity of the FGF signaling transducer protein in human tooth germ was much higher than that of in mouse. Our results provided important FGF singling information in the developing process, pinpoint to the domains where the downstream target genes of FGF signaling can be sought, and enlightened our knowledge about the nature of FGF signaling in human tooth germ. PMID- 26266342 TI - Histone Peptide Recognition by KDM5B-PHD1: A Case Study. AB - A detailed understanding of the energetic contributions to histone peptide recognition would be valuable for a better understanding of chromatin anchoring mechanisms and histone diagnostic design. Here, we probed the energetic contributions to recognize the same unmodified histone H3 by three different plant homeodomain (PHD) H3K4me0 readers: hKDM5B-PHD1 (first PHD finger of hKDM5B), hBAZ2A-PHD, and hAIRE-PHD1. The energetic contributions of residues differ significantly from one complex to the next. For example, H3K4A substitution completely aborts the formation of the hAIRE-histone peptide complex, while it has only a small destabilizing effect on binding of the other readers, even though H3K4 methylation disrupts all three complexes. Packing density suggests that methylation of more tightly packed Lys/Arg residues can disrupt binding, even if the energetic contribution is small. The binding behavior of hKDM5B-PHD1 and hBAZ2A-PHD is similar, and like PHD H3R2 readers, both possess a pair of Asp residues in the treble clef for interaction with H3R2. PHD subtype sequences, especially the tandem PHD-PHD fingers, show enrichment in the treble clef Asp residues, suggesting that it is a subtype-specific property. These Asp residues make significant energetic contributions to the formation of the hKDM5B-histone peptide complex, suggesting that there are interactions in addition to those reported in the recent NMR structure. However, the presence of the treble clef Asp in PHD sequences may not always be sufficient for histone peptide binding. This study showcases reader-histone peptide interactions in the context of residue conservation, energetic contributions, interfacial packing, and sequence-based reader subtype predictability. PMID- 26266343 TI - Bivalirudin Anticoagulant Therapy With or Without Platelet Glycoprotein IIb/IIIa Inhibitors During Transcatheter Coronary Interventional Procedures: A Meta Analysis. AB - The safety and effectiveness of using the direct thrombin inhibitor bivalirudin during transcatheter coronary interventional procedures remains uncertain.This study aimed to systematically assess anticoagulation with bivalirudin alone or bivalirudin plus glycoprotein (GP) IIb/IIIa inhibitors (bivalirudin-based anticoagulant therapy) in patients undergoing percutaneous coronary intervention (PCI) procedures by a meta-analysis of randomized controlled trials (RCTs).Systematical searches of the MEDLINE, EMBASE, and Cochrane databases were conducted. RCTs comparing bivalirudin-based anticoagulant therapy with a comparable heparin therapy in patients undergoing PCI were eligible. Risk ratios (RRs) with 95% confidence intervals (CIs) served as summary statistics.A total of 38,096 patients from 17 RCTs were randomized to the bivalirudin group (n = 18,878) or heparin group (n = 19,218) in the meta-analysis. No significant differences in death, myocardial infarction or reinfarction, ischemia-driven revascularization, or in-stent thrombosis were observed between the 2 groups (all P > 0.05). Notably, bivalirudin-based therapy showed a highly significant 34% decrease in the incidence of major bleeding (RR = 0.66; 95% CI 0.54-0.81; P < 0.001) and a 28% reduction in the need for blood transfusion (RR = 0.72; 95% CI 0.56-0.91; P < 0.01). Meta-regression analyses demonstrated that additional administration of GP IIb/IIIa receptor inhibitors (P = 0.01), especially eptifibatide (P = 0.001) and tirofiban (P = 0.002), was likely to increase the major bleeding risk associated with bivalirudin.Bivalirudin, in comparison to heparin, is associated with a markedly lower risk of major bleeding, and the additional use of GP IIb/IIIa inhibitors may weaken this benefit. PMID- 26266344 TI - Tracheobronchial Stenoses in Granulomatosis With Polyangiitis (Wegener's): A Report on 26 Cases. AB - Tracheobronchial stenoses (TBSs) are potentially severe manifestations of granulomatosis with polyangiitis (Wegener's) (GPA) that usually respond poorly to corticosteroids and immunosuppressive agents. We describe 26 GPA patients with >=1 tracheal (mainly subglottic, SGS) and/or bronchial stenosis(ses) (BS(s)).Sixteen patients had solitary SGS and 10 had >=1 BS(s). The male/female sex ratio was 9:17, and the median age at GPA diagnosis was 32 years (3:13 and 28 years, respectively, for SGS patients). Antineutrophil cytoplasm antibodies were proteinase 3-positive in 65.5% of the patients (50% of those with SGS).Despite conventional GPA therapy, 62% patients experienced >=1 stenosis relapse(s) (81% of SGS patients, for a total of 1-8 relapses per patient). None of the several systemic or endoscopic treatments prevented future relapses. Cyclophosphamide induction therapy was effective in 4/6 patients with BS(s) and in 1 patient with SGS among the 7 treated. After many relapses, rituximab achieved remission in 3/4 SGS patients. Endoscopic treatments (dilation, laser, corticosteroid injection, etc.) had only transient efficacy. Other GPA manifestations relapsed independently of TBSs. One SGS patient died of acute respiratory distress syndrome.Our findings confirmed that TBSs are severe GPA manifestations that evolve independently of other organ involvements and do not respond to conventional systemic regimens. As previously described, our population was younger and comprised more females than usual GPA patients, especially those with SGS.The small number of patients and the wide variety of local and systemic treatments prevent us from drawing definitive conclusions about the contribution of each procedure. However, cyclophosphamide seemed to effectively treat BSs, but not SGS, and rituximab may be of interest for SGS management. PMID- 26266345 TI - Genetic Association Studies Reporting on Variants in the C-Reactive Protein Gene and Coronary Artery Disease: A Meta-Analysis. AB - C-reactive protein (CRP) is a commonly used inflammatory marker and elevated CRP levels are shown to increase the risk of coronary artery disease (CAD). Sequence variations in the CRP gene believed to influence the protein levels have been extensively investigated in CAD community. Most of the published studies, however, have reported mixed findings. The objective of the present study was to examine the associations of CRP variants (+942G>C, -717A>G, +1444C>T) with genetic risk of CAD by use of a meta-analysis.The human case-control studies were identified through online search, hand search, and contacting the authors of original articles. We performed both random-effect and fixed-effect meta-analysis to estimate CAD risk (odds ratios, OR). This analysis combined 16 studies in total. We found +942G>C was not associated with CAD risk when all data were pooled together, nor did we find a significant association in subgroup analyses. Meta-analysis of +1444C>T studies showed a similar trend. However, a borderline association with CAD risk was revealed for -717A>G (random-effect: OR = 0.53, 95% CI = 0.28-1.00 for the homozygous model; random-effect: OR = 0.51, 95% CI = 0.26 1.00 for the recessive model).These data suggest that the CRP gene variants examined may not modulate CAD risk. PMID- 26266346 TI - Clinical Spectrum Time Course in Anti Jo-1 Positive Antisynthetase Syndrome: Results From an International Retrospective Multicenter Study. AB - Anti Jo-1 antibodies are the main markers of the antisynthetase syndrome (ASSD), an autoimmune disease clinically characterized by the occurrence of arthritis, myositis, and interstitial lung disease (ILD). These manifestations usually co occur (for practical purpose complete forms) in the same patient, but cases with only 1 or 2 of these findings (for practical purpose incomplete forms) have been described. In incomplete forms, the ex novo occurrence of further manifestations is possible, although with frequencies and timing not still defined. The aim of this international, multicenter, retrospective study was to characterize the clinical time course of anti Jo-1 positive ASSD in a large cohort of patients. Included patients should be anti Jo-1 positive and with at least 1 feature between arthritis, myositis, and ILD. We evaluated the differences between complete and incomplete forms, timing of clinical picture appearance and analyzed factors predicting the appearance of further manifestations in incomplete ASSD. Finally, we collected 225 patients (58 males and 167 females) with a median follow-up of 80 months. At the onset, complete ASSD were 44 and incomplete 181. Patients with incomplete ASSD had frequently only 1 of the classic triad findings (110 cases), in particular, isolated arthritis in 54 cases, isolated myositis in 28 cases, and isolated ILD in 28 cases. At the end of follow-up, complete ASSD were 113, incomplete 112. Only 5 patients had an isolated arthritis, only 5 an isolated myositis, and 15 an isolated ILD. During the follow-up, 108 patients with incomplete forms developed further manifestations. Single main feature onset was the main risk factor for the ex novo appearance of further manifestation. ILD was the prevalent ex novo manifestation (74 cases). In conclusion, ASSD is a condition that should be carefully considered in all patients presenting with arthritis, myositis, and ILD, even when isolated. The ex novo appearance of further manifestations in patients with incomplete forms is common, thus indicating the need for an adequate clinical and instrumental follow-up. Furthermore, the study clearly suggested that in ASSD multidisciplinary approach involving Rheumatology, Neurology, Pneumology, and Internal Medicine specialists is mandatory. PMID- 26266347 TI - A Cohort Study of Myocardial Perfusion Imaging in Veteran Patients Without Symptoms: Contributing Factors and Results of Testing. AB - Myocardial perfusion imaging (MPI) is commonly used to detect ischemia. Concerns about silent ischemia may encourage orders for MPI in asymptomatic patients. Factors contributing to this practice are poorly described and the clinical utility is questionable.We conducted a single center retrospective cohort investigation on Veterans who underwent MPI between December 2010 and July 2011. We gathered data on symptoms, baseline characteristics, results of MPI, and cardiovascular events within 1 year. MPI were categorized using 2009 appropriate use criteria (AUC).Of 592 patients, 127 (21.5%) had no symptoms at the time of MPI. Comparing symptomatic and asymptomatic patients, no differences were observed in baseline characteristics except abnormal ECG, more common in asymptomatic patients (n = 86, 67.7% vs. n = 232, 49.9% for symptomatic patients, P < 0.0001). Asymptomatic MPI were more commonly inappropriate (n = 26, 21.5% vs. n = 31, 6.7% for appropriate/uncertain, P < 0.0001). Detection of ischemia between patients with and without symptoms was not different (P = 0.86); however, among asymptomatic MPI that also demonstrated ischemia, none were inappropriate (n = 10 appropriate, n = 7 uncertain). In multivariate regression, 2 factors were associated with asymptomatic status, abnormal ECG (odds ratio [OR] 2.29, 95% confidence interval [CI] 1.5-3.49) and age over the median (OR 0.63, 95% CI: 0.41 0.95).A substantial portion of MPI tests are ordered for patients without symptoms. When compared to symptomatic patients, MPI for asymptomatic patient were more commonly inappropriate; however, the prevalence of ischemia was similar. MPI may be clinically relevant in some asymptomatic patients and decisions to test should be based on the AUC. PMID- 26266348 TI - Gadolinium Ethoxybenzyl Diethylenetriamine Pentaacetic Acid (Gd-EOB-DTPA) Enhanced Magnetic Resonance Imaging and Multidetector-Row Computed Tomography for the Diagnosis of Hepatocellular Carcinoma: A Systematic Review and Meta-analysis. AB - The purpose of this meta-analysis was to compare the diagnostic accuracy of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) and multidetector-row computed tomography (MDCT) for hepatocellular carcinoma (HCC).Medline, Cochrane, EMBASE, and Google Scholar databases were searched until July 4, 2014, using combinations of the following terms: gadoxetic acid disodium, Gd-EOB-DTPA, multidetector CT, contrast-enhanced computed tomography, and magnetic resonance imaging. Inclusion criteria were as follows: confirmed diagnosis of primary HCC by histopathological examination of a biopsy specimen; comparative study of MRI using Gd-EOB-DTPA and MDCT for diagnosis of HCC; and studies that provided quantitative outcome data. The pooled sensitivity and specificity of the 2 methods were compared, and diagnostic accuracy was assessed with alternative-free response receiver operating characteristic analysis.Nine studies were included in the meta analysis, and a total of 1439 lesions were examined. The pooled sensitivity and specificity for 1.5T MRI were 0.95 and 0.96, respectively, for 3.0T MRI were 0.91 and 0.96, respectively, and for MDCT were 0.74 and 0.93, respectively. The pooled diagnostic odds ratio for 1.5T and 3.0T MRI was 242.96, respectively, and that of MDCT was 33.47. To summarize, Gd-EOB-DTPA-enhanced MRI (1.5T and 3.0T) has better diagnostic accuracy for HCC than MDCT. PMID- 26266350 TI - CT-Guided Percutaneous Radiofrequency Thermocoagulation for Recurrent Trigeminal Neuralgia After Microvascular Decompression: A Cohort Study. AB - This article evaluates the long-term outcomes of computed tomography (CT)-guided percutaneous radiofrequency thermocoagulation (PRT) for patients with recurrent trigeminal neuralgia (TN) after microvascular decompression (MVD).This is a retrospective study of 41 patients with intractable TN who after MVD underwent CT guided PRT procedures between 2002 and 2012.The mean length of follow-up after PRT was 44.4 months. Immediate pain relief was in 37 patients (90.2%); the percentage of patients who remained in "excellent" or "good" pain relief condition after CT-guided PRT procedure was 85% at 1 year, 80% at 2 years, 51% at 5 years, and 41% at 10 years. Six patients received the second PRT and all achieved "excellent" or "good" pain relief. In total, 34 of these patients (82.9%) received multi-PRT procedure and remained satisfied with their pain relief during the follow-up period. Postoperative complications included facial numbness in 36 patients, limited eyes opening in 1 patient, ear paresthesia in 1 patient, no tears in 1 patient, and taste hypesthesia in 1 patient; these symptoms were all improved in the process of follow-up and their life had not severely affected. No mortality was observed during and after CT-guided PRT procedures.CT-guided PRT should be considered as an alternative treatment for patients with recurrent TN after MVD. PMID- 26266351 TI - Association of Zinc Finger, C3HC-Type Containing 1 (ZC3HC1) rs11556924 Genetic Variant With Hypertension in a Finnish Population, the TAMRISK Study. AB - In a recent genome-wide association study, the zinc finger, C3HC-type containing 1 (ZC3HC1) polymorphism was strongly associated with coronary artery disease (CAD) by an unknown mechanism. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is related with CAD through low-density lipoprotein (LDL) metabolism. The association of both of the above genetic variants with hypertension was studied in a Finnish 50-year-old cohort.A total of 325 hypertensive cases and 444 nonhypertensive controls were obtained from the Tampere adult population cardiovascular risk study. Samples were genotyped for ZC3HC1 rs11556924 and PCSK9 rs11206510 polymorphisms using Competitive Allele Specific PCR technique. A subpopulation that had available follow-up data from ages of 40, 45, and 50 years was also analyzed.ZC3HC1 rs11556924 (C > T) genotype CC was associated with hypertension compared with the T-allele carriers (P = 0.013). PCSK9 rs11206510 (T > C) genotype was not associated with hypertension. Its major TT-genotype was associated with higher total cholesterol (P = 0.044) and LDL (P = 0.029) compared with the C-allele.We report for the first time that ZC3HC1 rs11556924 was associated with essential hypertension in 50-year-old patients. Although PCSK9 rs11206510 was not associated with hypertension, our study confirms its association with serum cholesterol levels. PMID- 26266349 TI - A New Insight Into Sudden Cardiac Death in Young People: A Systematic Review of Cases of Takotsubo Cardiomyopathy. AB - Takotsubo cardiomyopathy (TTC) causes sudden cardiac death and has garnered increased attention worldwide in recent years. However, few studies have clearly classified the risk factors for this disease, including gender, race and morbidity, as well as the physical and mental stressors that can exacerbate the disease, particularly in young patients. To better analyze the characteristics of young TTC patients, we performed a systematic review of reported cases involving young patients.A computer-assisted search was performed using prominent electronic medical information sources to identify literature published between January 1965 and December 2013. Relevant studies containing clinical data of young TTC patients were included.Ninety-six records that included information about 104 cases were ultimately selected for our review. Several of the following results were noted: First, physical stress was more likely to exacerbate TTC than was mental stress in young patients. Second, more female than male TTC patients were noted among both young patients and the general population. Third, ethnicity appears to play no role in the disease, as no significant differences were noted among individuals of different races with respect to clinical characteristics, morbidity or stressors. Fourth, the clinical manifestations of TTC were similar to those of other cardiac diseases, including coronary heart disease. However, TTC may be detected using the combination of echocardiography and ventriculography.Clinicians should consider TTC if young patients present with symptoms similar to those of coronary heart disease so that harmful treatments such as coronary artery stent placement may be avoided. Moreover, the answers to questions regarding the clinical diagnostic criteria, etiology, pathophysiology, and the management of this syndrome in youth remain unclear; therefore, further research is needed. PMID- 26266352 TI - Esophageal Perforation and Acute Bacterial Mediastinitis: Other Causes of Chest Pain That Can Be Easily Missed. AB - Esophageal perforation is a rare condition that is commonly missed. Male gender and alcohol use are predisposing risk factors. Most of the cases are iatrogenic or traumatic; nonetheless, spontaneous cases are not uncommon. It typically occurs after vomiting or straining as the increased intra-abdominal pressure transmits into the esophagus and results in the tear. One of the main complications is acute bacterial mediastinitis from contamination with esophageal flora. This condition can be life-threatening because it is very frequently misdiagnosed and appropriate management is often delayed.A 49-year-old man presented with worsening sudden-onset interscapular back pain that then changed to chest pain with odynophagia and was found to have fever and leukocytosis.Chest computed tomography revealed signs of mediastinitis with possible esophageal perforation. He reported symptoms started 2 days ago after lifting of heavy objects. Empiric antimicrobial was begun with conservative management and avoidance of oral intake. Barium esophagram and esophagogastroduodenoscopy revealed no signs of perforation or inflammation. His symptoms resolved and he gradually resumed oral intake. Blood cultures grew Methicillin-sensitive Staphylococcus aureus and he was discharged on appropriate antibiotics for 4 weeks. He did well on follow-up 3 months after hospitalization.The case highlights the importance of considering esophageal etiologies of chest pain. PMID- 26266353 TI - Fatal Events in Cancer Patients Receiving Anticoagulant Therapy for Venous Thromboembolism. AB - In cancer patients treated for venous thromboembolism (VTE), including deep-vein thrombosis (DVT) and pulmonary embolism (PE), analyzing mortality associated with recurrent VTE or major bleeding is needed to determine the optimal duration of anticoagulation.This was a cohort study using the Registro Informatizado de Enfermedad TromboEmbolica (RIETE) Registry database to compare rates of fatal recurrent PE and fatal bleeding in cancer patients receiving anticoagulation for VTE.As of January 2013, 44,794 patients were enrolled in RIETE, of whom 7911 (18%) had active cancer. During the course of anticoagulant therapy (mean, 181 +/ 210 days), 178 cancer patients (4.3%) developed recurrent PE (5.5 per 100 patient-years; 95% CI: 4.8-6.4), 194 (4.7%) had recurrent DVT (6.2 per 100 patient-years; 95% confidence interval [CI]: 5.3-7.1), and 367 (8.9%) bled (11.3 per 100 patient-years; 95% CI: 10.2-12.5). Of 4125 patients initially presenting with PE, 43 (1.0%) died of recurrent PE and 45 (1.1%) of bleeding; of 3786 patients with DVT, 19 (0.5%) died of PE, and 55 (1.3%) of bleeding. During the first 3 months of anticoagulation, there were 59 (1.4%) fatal PE recurrences and 77 (1.9%) fatal bleeds. Beyond the third month, there were 3 fatal PE recurrences and 23 fatal bleeds.In RIETE cancer patients, the rate of fatal recurrent PE or fatal bleeding was much higher within the first 3 months of anticoagulation therapy. PMID- 26266354 TI - Association Between Alcohol Consumption and the Risk of Barrett's Esophagus: A Meta-Analysis of Observational Studies. AB - The association between alcohol consumption and Barrett's esophagus (BE) remained uncertain and controversial in the previous studies. We performed a meta-analysis of observational studies to clarify the association.We searched PubMed, Web of Science, and Embase for studies on alcohol consumption and risk of BE published before February 2015. A total of 20 studies reporting the association between alcohol consumption and the risk of BE were identified. Subgroup analyses, meta regression analyses, sensitivity analyses, and publication bias tests were also performed. Several results from individual studies were pooled using a dose response meta-analysis.A total of 20 studies involving 45,181 participants and 4432 patients of BE were included in the meta-analysis. No association was found between alcohol consumption and BE (relative risk [RR] = 1.10, 95% confidence interval [CI] 0.96-1.27, I = 48.60%) in our study. In subgroup analysis, alcohol consumption was associated with an increased risk of BE in men (RR = 1.35, 95% CI 1.13-1.61, I = 0.00%) and Asian population (RR = 1.60, 95% CI 1.03-2.49, I = 60.60%). In beverage-specific consumption analysis, liquor was associated with an increased risk of BE (RR = 1.16, 95% CI 1.02-1.32, I = 0.00%). Multivariate meta regression analysis suggested that geographic area, and adjusted age, sex, body mass index, and smoke, might explain 70.75% of the heterogeneity between the studies. We also found the inverse association (RR = 0.84, 95% CI 0.72-0.98, I = 0.00%) between alcohol consumption and BE among subjects when compared with population controls.Overall, there was no significant association between alcohol consumption and BE. Alcohol consumption may be a risk factor of BE in men and Asian population, and liquor consumption may also increase the risk of BE. Significant inverse association was observed between alcohol consumption and BE, for comparisons with population controls. PMID- 26266356 TI - Braun Enteroenterostomy Following Pancreaticoduodenectomy: A Systematic Review and Meta-Analysis. AB - Pancreaticoduodenectomy (PD) holds high postoperative morbidity. How to resolve this issue is challenged. An additional anastomosis (Braun enteroenterostomy) following PD may decrease the postoperative morbidity, but holds conflicting results. The objective of this study is to investigate the advantages and disadvantages of Braun enteroenterostomy in PD.Clinical studies compared perioperative outcomes between the Braun group and the non-Braun group following PD before December 21, 2014 were retrieved and filtered from PubMed, EMBASE, Web of Science, the Cochrane Library, and Chinese electronic databases (VIP database, WanFang database, and CNKI database). Relevant data were extracted according to predesigned sheets. Blood loss, operating time, and postoperative mortality and morbidity were evaluated using odds ratio (OR), weighted mean difference, or standard mean difference (SMD).Ten studies concerning 1614 patients were included. No significant differences between the Braun and the non-Braun group were identified in mortality (OR: 0.65, 95% confidence interval [CI]: 0.26-1.60), intraoperative blood loss (SMD: -0.035, 95% CI: -0.253 to 0.183), postoperative pancreatic fistula (POPF) (OR: 0.67, 95% CI: 0.35-1.67), bile leakage (OR: 0.537, 95% CI: 0.287-1.004), postoperative gastrointestinal hemorrhage (OR: 1.17, 95% CI: 0.578-2.385), intraabdominal abscesses (OR: 0.793, 95% CI: 0.444-1.419), wound complications (OR: 0.806, 95% CI: 0.490-1.325), and hospital stay (SMD: 0.098, 95% CI: -0.23 to 0.033). Braun enteroenterostomy extended operating time (SMD: 0.39, 95% CI: 0.02-0.78), but it was associated with lower reoperation rate (OR: 0.380, 95% CI: 0.149-0.968), lower morbidity rate (OR: 0.66, 95% CI: 0.49 0.91), lower clinically relevant delayed gastric emptying (Grades B and C) (OR: 0.375, 95% CI: 0.164-0.858), lower nasogastric tube reinsertion (OR: 0.436, 95% CI: 0.232-0.818), and less postoperative vomiting (OR: 0.444, 95% CI: 0.262 0.755).Braun enteroenterostomy can be safely performed during PD. It is beneficial for patients and could be recommended in PD from the current published data.PROSPERO registration number: CRD42015016198. PMID- 26266355 TI - Pseudo-Peritoneal Carcinomatosis Presentation of a Crystal-Storing Histiocytosis With an Unmutated Monoclonal kappa Light Chain. AB - Crystal-storing histiocytosis (CSH) is a rare complication of monoclonal gammopathies caused by accumulation of crystalline material inside macrophages, and it may result in a variety of clinical manifestations depending on the involved organs. Although immunoglobulin kappa light chains (LCs) seem to be the most frequent pathogenic component, very few molecular data are currently available.A 69-year-old man presented with a very poor performance status. Remarkable features were mesenteric lymph node enlargement and proteinuria, including a monoclonal kappa LC. Light and electron microscopy studies revealed the presence of crystals within macrophages in the lymph nodes, bone marrow, and kidney, leading to the diagnosis of CSH. The pathogenic kappa LC variable domain sequence was identical to the germline Vk3-2001/Jk201 gene segments, without any somatic mutation, suggesting an extra-follicular B cell proliferation.The patient was successfully treated with 4 cycles of bortezomib and dexamethasone. After a 12-month follow-up, he remains in hematological and renal remission.CSH may present as pseudo-peritoneal carcinomatosis and relate to a monoclonal kappa LC encoded by an unmutated gene. Bortezomib-based therapy proved efficacious in this case. PMID- 26266357 TI - Cardiac Rehabilitation in Real Life. AB - Participation in cardiac rehabilitation programs (CRPs) improves prognosis in patients with coronary artery disease (CAD). However, not much is known about the effectiveness of CRP in real life. The aim of this analysis was to identify factors related to the referral to CRP following hospitalization for CAD and estimate the effectiveness of the programs in real life.Medical records of 1061 consecutive patients aged <=80 years, hospitalized due to an acute coronary syndrome or for a myocardial revascularization procedure in 5 hospitals serving the city and surrounding counties, were reviewed and 611 patients were interviewed 6-18 months posthospitalization.Of 611 patients participating in the interview, 212 (34.7%) were referred following the hospitalization to a center providing CRP. Age, hospitalization in a teaching hospital, and index diagnosis were independently related to being granted a referral. Among the referred patients, 86.3% participated in the CRP. Participation in CRP was related to the lower probability of having high total cholesterol (23% vs 32%, P < 0.05), fasting glucose (11% vs 18%, P = 0.05), HbA1c (8% vs 16%, P = 0.05), and body mass index (27% vs 37%, P < 0.05). Generally, the effect of the CRP was significant in participants with a higher education, but not in those with a low education level. Other factors were not significantly related to the effectiveness of CRP.This study shows that CRPs are effective, but underused in Poland. The participant's education level may influence the effectiveness of CRP. Therefore, in order to increase the impact of CRP, the content of such programs should vary depending on the education level of the participants. PMID- 26266358 TI - Risk Factors for Pterygium in Korea: The Korean National Health and Nutrition Examination Survey V, 2010-2012. AB - The aim of this study is to report general and age-specific risk factors for pterygium prevalence in the Korean population.This in an observational case series study.Data from total 24,812 participants (age 40 years or older) from the Korean National Health and Nutrition Examination Surveys conducted from 2010 to 2012 were retrieved. After applying exclusion criteria, data from 13,204 participants (821 with pterygium and 12,383 without) were used for univariate and multivariate analyses. General risk factors were identified and participants were grouped by decade: 40 s, 50 s, 60 s, 70 s, and 80+. Age-specific risk factors were investigated for each group.After univariate analysis, 2 multiple regression models were constructed. Model 1: age + sex + spherical equivalent (SE) + sun exposure hours + occupation (indoor vs outdoor) + residency area (rural vs urban) + education level; model 2: age + sex + SE + sun exposure hours. In model 1, older age (odds ratio [OR]: 1.05 95% confidence interval [CI]: 1.05-1.06), male gender (OR: 1.28, 95% CI: 1.01-1.61), and longer sun exposure hours (OR: 1.47, 95% CI: 1.11-1.94) were significant risk factors for pterygium prevalence whereas higher level of education (elementary school vs college, OR: 3.98, 95% CI: 2.24 7.06) and urban residency (vs rural residency, OR: 0.56, 95% CI: 0.45-0.70) were protective factors. Higher SE (OR 1.11, 95% CI: 1.03-1.19) refractive error was considered a risk factor when using model 2 for the analysis. Age-specific risk factors were different in each age group. Male gender was associated with higher pterygium prevalence in younger age groups while longer sun exposure (5+ hours/day) increased pterygium prevalence in older age groups.Previously characterized risk factors were also found in this large population study. However, we found that risk factors may vary according to the age group. Myopic eyes were found to have lower prevalence than hyperopic eyes. PMID- 26266359 TI - Intraoperative Management of an Incidentally Identified Ectopic Ureter Inserting Into the Prostate of a Patient Undergoing Radical Prostatectomy for Prostate Cancer: A Case Report. AB - Congenital variations in urinary tract anatomy present unique surgical challenges when they present without prior knowledge. Ectopic ureters occur as a rare anatomic variation of the urinary tract and are often associated with duplicated renal collecting systems. While the condition is uncommon, even more atypical is its discovery and subsequent diagnosis during surgical intervention for treatment of localized prostate cancer.We describe the intraoperative management of a unique case of bilateral ectopic ureters, with a right-sided ureter inserting into the prostate of a 54-year-old male undergoing robotic-assisted radical prostatectomy. While unknown at the time of surgery, this right-sided ureter was associated with a nonfunctioning right upper renal moiety of a duplex renal collecting system. This aberration was discovered intraoperatively and confirmed with imaging, and a robotic-assisted radical prostatectomy with right distal ureterectomy was performed. PMID- 26266360 TI - Evidence for Chronic Kidney Disease-Mineral and Bone Disorder Associated With Metabolic Pathway Changes. AB - Abnormalities in the levels of calcium, phosphorus, and parathyroid hormone (PTH) in serum are typical for patients with chronic kidney disease (CKD). They are used routinely to predict the onset of CKD-mineral and bone disorder (MBD). However, CKD-MBD associated with metabolic pathway imbalance is not well understood.The objective of the study was to identify endogenous metabolic signatures in patients with intact PTH using mass spectrometry-based metabolomics. This study was a cross-sectional study. Ultra performance liquid chromatography-Quadrupole Time-of-Flight/mass spectrometry-based metabolic profiling was employed to analyze serum samples from 19 disease controls (DCs) (intact parathyroid hormone [iPTH] 150-300 pg/mL) and 19 secondary hyperparathyroidism (SHPT) patients (iPTH >300 pg/mL) (the training data set) to identify metabolic biomarkers for CKD-MBD. Then, another set of samples including 19 DCs (iPTH 150-300 pg/mL) and 19 SHPT patients (iPTH >300 pg/mL) (the test data set) were used to validate the potential biomarkers identified.Metabolic profiling analyses revealed different patterns of endogenous metabolites between the SHPT and the DC groups. A total of 32 unique metabolites were identified and 30 metabolites were elevated in the iPTH compared with control serum pools. Cytidine and L-phenylalanine were downregulated in the SHPT patients. The metabolic signatures identified were assessed respectively by an internal 10-fold cross validation with an accuracy of 91.4% and an external validation with an accuracy of 71.1%, a sensitivity of 73.7%, and a specificity of 68.4%.Mass spectrometry-based metabolomic analyses for SHPT patients promises immense potential for early diagnosis and therapy monitoring. Our results indicated that the onset of CKD-MBD is associated with pathway changes of protein synthesis and metabolism, amino acid metabolism, energy metabolism, and steroid hormone metabolism, with obvious promise for better understanding the pathogenesis of this disease. Several metabolic biomarkers were identified, which warrant further development. PMID- 26266361 TI - IgG4-Related Disease: Results From a Multicenter Spanish Registry. AB - IgG4-related disease (IgG4-RD) is a rare entity consisting of inflammation and fibrosis that has been described in multiple organs. Concrete diagnostic criteria have been established recently and there is a lack of large series of patients.To describe the clinical presentation, histopathological characteristics, treatment and evolution of a series of IgG4-RD Spanish patients.A retrospective multicenter study was performed. Twelve hospitals across Spain included patients meeting the current 2012 consensus criteria on IgG4-RD diagnosis.Fifty-five patients were included in the study, 38 of whom (69.1%) were male. Median age at diagnosis was 53 years. Thirty (54.5%) patients were included in the Histologically Highly Suggestive IgG4-RD group and 25 (45.5%) in the probable IgG4-RD group. Twenty-six (47.3%) patients had more than 1 organ affected at presentation. The most frequently affected organs were: retroperitoneum, orbital pseudotumor, pancreas, salivary and lachrymal glands, and maxillary sinuses.Corticosteroids were the mainstay of treatment (46 patients, 83.6%). Eighteen patients (32.7%) required additional immunosuppressive agents. Twenty-four (43.6%) patients achieved a complete response and 26 (43.7%) presented a partial response (<50% of regression) after 22 months of follow-up. No deaths were attributed directly to IgG4-RD and malignancy was infrequent.This is the largest IgG4-RD series reported in Europe. Patients were middle-aged males, with histologically probable IgG4-RD. The systemic form of the disease was frequent, involving mainly sites of the head and abdomen. Corticosteroids were an effective first line treatment, sometimes combined with immunosuppressive agents. Neither fatalities nor malignancies were attributed to IgG4-RD. PMID- 26266362 TI - Efficacy of Adenosine in Patients With Acute Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A PRISMA-Compliant Meta-Analysis. AB - Whether adenosine offers cardioprotective effects when used as an adjunctive therapy for patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) remains controversial.To evaluate, via meta-analysis, the efficacy of adenosine in patients with AMI undergoing PCI.Randomized controlled trials (RCTs) published in Medline, Embase, and the Cochrane Central Register of Controlled Trials.RCTs of patients with AMI undergoing primary PCI, comparing adenosine treatment and placebo groups and reporting mortality, thrombolysis in myocardial infarction (TIMI) flow grade, myocardial blush grade (MBG), re-infarction, left-ventricular ejection fraction (LVEF), ST-segment elevation resolution (STR), recurrent angina, or heart failure (HF).Risk of bias was assessed by the Cochrane guidelines and publication bias by Egger's test. For studies reported in multiple publications, the most complete publication was used. Arms using different dosing schedules were merged. Mean differences (MDs) or risk ratios (RRs) were determined.Data were extracted from 15 RCTs involving 1736 patients. Compared with placebo, adenosine therapy was associated with fewer occurrences of heart failure (RR: 0.65, 95% confidence interval [CI]: 0.43-0.97, P[REPLACEMENT CHARACTER]=[REPLACEMENT CHARACTER]0.03) and no-reflow (TIMI flow grade <3, RR: 0.62, 95% CI: 0.45-0.85, P[REPLACEMENT CHARACTER]=[REPLACEMENT CHARACTER]0.003; MBG[REPLACEMENT CHARACTER]=[REPLACEMENT CHARACTER]0-1, RR: 0.81; 95% CI: 0.67-0.98, P[REPLACEMENT CHARACTER]=[REPLACEMENT CHARACTER]0.03), more occurrences of STR (RR: 1.19, 95% CI: 1.07-1.31, P[REPLACEMENT CHARACTER]<[REPLACEMENT CHARACTER]0.00001), but no overall improvement of LVEF (MD: 2.29, 95% CI: -0.09 to 4.67, P[REPLACEMENT CHARACTER]=[REPLACEMENT CHARACTER]0.06). Adenosine improved LVEF in the intravenous subgroup and the regular-dose intracoronary (IC) subgroup (0.24 2.25[REPLACEMENT CHARACTER]mg) compared with placebo (MD: 2.68, 95% CI: 0.66 4.70, P[REPLACEMENT CHARACTER]=[REPLACEMENT CHARACTER]0.009). Adenosine was associated with a poorer LVEF in the high-dose (4-6[REPLACEMENT CHARACTER]mg) IC subgroup (MD: -2.40; 95% CI: -4.72 to -0.09, P[REPLACEMENT CHARACTER]=[REPLACEMENT CHARACTER]0.04). There was no significant evidence that adenosine reduced rates of all-cause mortality, cardiovascular mortality or re infarction after PCI.Adenosine dosage and administration routes, baseline profiles, and endpoints differed among included RCTs. Performance, publication, and reporting biases remain possible.Adenosine therapy appears to improve several outcomes in patients with AMI after PCI, but there is no evidence that adenosine can reduce mortality rates. PMID- 26266363 TI - Application Value of a 6-Type Classification System for Common Hepatic Artery Absence During Laparoscopic Radical Resections for Gastric Cancer: A Large-Scale Single-Center Study. AB - The common hepatic artery (CHA) is an important blood vessel that must be vascularized during D2 lymphadenectomies for gastric cancer. When the CHA is absent, the risk of vascular injury increases.To explore the anatomic classification of CHA absence and its application value in laparoscopic radical resections for gastric cancer.Clinical data were collected prospectively from 2170 gastric cancer patients from June 2007 to December 2013, and the data were analyzed retrospectively. The anatomy of CHA absence was assessed synthetically by combining preoperative CT scans and intraoperative images, which were classified according to the anatomy of replaced hepatic arteries (RHAs) and were grouped into the early-year group (2007-2011) and the later-year group (2012 2013) based on the year in which the operation was performed.CHA absence was noted in 38 cases (1.8%) and was classified into 6 types: type I (replaced CHA [RCHA] from the superior mesenteric artery [SMA] with retropancreatic course, 28), type II (RCHA from the SMA with circumambulated course, 1), type III (RCHA from the aortic artery, 1), type IV (replaced left hepatic artery [RLHA] from the left gastric artery [LGA] and replaced right hepatic artery [RRHA] from the SMA, 5), type V (RLHA from the LGA and RRHA from the celiac artery, 2), and type VI (RLHA from the aberrant gastroduodenal artery and RRHA from the SMA, 1). Of the 38 cases, 17 cases (44.7%) belong to the early-year group, and 21 cases (55.3%) belong to the later-year group. The vascular injury rate was significantly lower in the later-year group than in the early-year group (4.8% [1/21] vs 41.2% [7/17], P = 0.005]. Additionally, the alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) values were significantly lower in the later-year group than in the early-year group on postoperative day 3 (all P < 0.05).A 6-type anatomic classification system can be used to demonstrate variations in features resulting from CHA absence in detail. Knowledge regarding a patient's classification is helpful for surgeons, and vascular injury and liver function damage may be reduced in patients who are properly classified prior to surgery. PMID- 26266364 TI - Symptomatic Atherosclerotic Disease and Decreased Risk of Cancer-Specific Mortality: A Prospective, Population-Based Study (NEDICES). AB - The few studies that have assessed the association between symptomatic atherosclerotic disease and risk of cancer have had conflicting results. In addition, these studies ascertained participants either from treatment settings (ie, service-based studies) or by using a records linkage system (ie, medical records of patients evaluated at clinics or hospitals) and, therefore, were prone to selection bias. Our purpose was to estimate the risk of cancer mortality in a large population-based sample of elderly people, comparing participants with symptomatic atherosclerotic disease (atherosclerotic stroke and coronary disease) to their counterparts without symptomatic atherosclerotic disease (ie, controls) in the same population.In this population-based, prospective study (Neurological Disorders of Central Spain, NEDICES), 5262 elderly community-dwelling participants with and without symptomatic atherosclerotic disease were identified and followed for a median of 12.1 years, after which the death certificates of those who died were reviewed.A total of 2701 (53.3%) of 5262 participants died, including 314 (68.6%) of 458 participants with symptomatic atherosclerotic disease and 2387 (49.7%) of 4804 controls. Cancer mortality was reported significantly less often in those with symptomatic atherosclerotic disease (15.6%) than in controls (25.6%) (P < 0.001). In an unadjusted Cox model, risk of cancer-specific mortality was decreased in participants with symptomatic atherosclerotic disease (HR = 0.74, 95% confidence interval [CI], 0.55-0.98, P = 0.04) vs. those without symptomatic atherosclerotic disease (reference group). In an adjusted Cox model, HR = 0.58; 95% CI, 0.38-0.89; P = 0.01.This population based, prospective study suggests that there is an inverse association between symptomatic atherosclerotic disease and risk of cancer mortality. PMID- 26266365 TI - Ossified Posterior Longitudinal Ligament With Massive Ossification of the Anterior Longitudinal Ligament Causing Dysphagia in a Diffuse Idiopathic Skeletal Hyperostosis Patient. AB - Descriptive case report.To report a case of a diffuse idiopathic skeletal hyperostosis (DISH) patient with both massive ossification of the anterior longitudinal ligament (OALL) leading to severe dysphagia as well as ossification of the posterior longitudinal ligament (OPLL) causing mild cervical myelopathy, warranting not only an anterior approach but also a posterior one.Although DISH can cause massive OALL in the cervical spine, severe dysphagia resulting from DISH is a rare occurrence. OALLs are frequently associated with OPLL. Treatment for a DISH patient with OPLL in setting of OALL-caused dysphagia is largely unknown.A 70-year-old man presented with severe dysphagia with mild cervical myelopathy. Neurological examination showed mild spastic paralysis and hyper reflex in his lower extremities. Plane radiographs and computed tomography of the cervical spine revealed a discontinuous massive OALL at C4-5 and continuous type OPLL at C2-6. Magnetic resonance imaging revealed pronounced spinal cord compression due to OPLL at C4-5. Esophagram demonstrated extrinsic compression secondary to OALL at C4-5.We performed posterior decompressive laminectomy with posterior lateral mass screw fixation, as well as both resection of OALL and interbody fusion at C4-5 by the anterior approach. We performed posterior decompressive laminectomy with posterior lateral mass screw fixation, as well as both resection of OALL and interbody fusion at C4-5 by the anterior approach. Severe dysphagia markedly improved without any complications.We considered that this patient not only required osteophytectomy and fusion by the anterior approach but also required decompression and spinal fusion by the posterior approach to prevent both deterioration of cervical myelopathy and recurrence of OALL after surgery. PMID- 26266366 TI - MicroRNA Expression Profile Reveals miR-17-92 and miR-143-145 Cluster in Synchronous Colorectal Cancer. AB - The expression of abnormal microRNA (miRNA, miR) is a ubiquitous feature of colorectal cancer (CRC). The pathological features and clinical behaviors of synchronous CRC have been comprehensively described; however, the expression profile of miRNA and small nucleolar RNA (snoRNA) in synchronous CRC has not been elucidated. In the present study, the expression profile of miRNA and snoRNA in 5 synchronous CRCs, along with the matched normal colorectal tissue was evaluated by microarray. Function and pathway analyses of putative targets, predicted from miRNA-mRNA interaction, were performed. Moreover, we analyzed clinicopathological and molecular characteristics of 22 patients with synchronous CRC and 579 solitary CRCs in a retrospective cohort study. We found a global dysregulation of miRNAs, including an oncogenic miR-17-92 cluster and oncosuppressive miR-143-145 cluster, and snoRNAs in synchronous CRC. Differential miRNA rather than snoRNA expression was robust enough to distinguish synchronous cancer from normal mucosa. Function analysis of putative targets suggested that miRNA clusters may modulate multiple effectors of oncogenic pathways involved in the pathogenesis of synchronous CRC. A comparison of normal mucosa between synchronous and solitary CRC suggested a differential genetic background of synchronous CRC from solitary CRC during carcinogenesis. Compared with solitary cancer patients, synchronous cases exhibited multiple extra-colonic cancers (P = 0.012), coexistence of adenoma (P = 0.012), microsatellite instability (P = 0.024), and less glucose transporter 1 (P = 0.037). Aberrant miRNA expression profiles could potentially be used as a diagnostic tool for synchronous CRC. Our findings represent the first comprehensive miRNA and snoRNA expression signatures for synchronous CRC, implicating that the miRNAs and snoRNAs may present therapeutic targets for synchronous CRC. PMID- 26266367 TI - The Lumbar Spine as a Dynamic Structure Depicted in Upright MRI. AB - Spinal canal stenosis is a dynamic phenomenon that becomes apparent during spinal loading. Current diagnostic procedures have considerable short comings in diagnosing the disease to full extend, as they are performed in supine situation. Upright MRI imaging might overcome this diagnostic gap.This study investigated the lumbar neuroforamenal diameter, spinal canal diameter, vertebral body translation, and vertebral body angles in 3 different body positions using upright MRI imaging.Fifteen subjects were enrolled in this study. A dynamic MRI in 3 different body positions (at 0 degrees supine, 80 degrees upright, and 80 degrees upright + hyperlordosis posture) was taken using a 0.25 T open configuration scanner equipped with a rotatable examination bed allowing a true standing MRI.The mean diameter of the neuroforamen at L5/S1 in 0 degrees position was 8.4 mm on the right and 8.8 mm on the left, in 80 degrees position 7.3 mm on the right and 7.2 mm on the left, and in 80 degrees position with hyperlordosis 6.6 mm (P < 0.05) on the right and 6.1 mm on the left (P < 0.001).The mean area of the neuroforamen at L5/S1 in 0 degrees position was 103.5 mm on the right and 105.0 mm on the left, in 80 degrees position 92.5 mm on the right and 94.8 mm on the left, and in 80 degrees position with hyperlordosis 81.9 mm on the right and 90.2 mm on the left.The mean volume of the spinal canal at the L5/S1 level in 0 degrees position was 9770 mm, in 80 degrees position 10600 mm, and in 80 degrees position with hyperlordosis 9414 mm.The mean intervertebral translation at level L5/S1 was 8.3 mm in 0 degrees position, 9.9 mm in 80 degrees position, and 10.1 mm in the 80 degrees position with hyperlordosis.The lordosis angle at level L5/S1 was 49.4 degrees in 0 degrees position, 55.8 degrees in 80 degrees position, and 64.7 mm in the 80 degrees position with hyperlordosis.Spinal canal stenosis is subject to a dynamic process, that can be displayed in upright MRI imaging. The range of anomalies is clinically relevant and dynamic positioning of the patient during MRI can provide essential diagnostic information which are not attainable with other methods. PMID- 26266368 TI - Botulinum Toxin Injection for Spastic Scapular Dyskinesia After Stroke: Case Series. AB - Spastic scapular dyskinesia after stroke is rare, which causes impaired shoulder active range of motion (ROM). To date, there has been no report about botulinum toxin injection to spastic periscapular muscles. This study presents botulinum toxin A injection for management of spastic periscapular muscles after stroke in 2 cases.This is a retrospective study of 2 cases of spastic scapular dyskinesia after stroke. Spasticity of periscapular muscles including rhomboid and lower trapezius was diagnosed by physical examination and needle electromyographic study. Botulinum toxin was injected into the spastic periscapular muscles under ultrasound imaging guidance.During the 3-week follow-up visit after injection, both patients showed increased shoulder active ROM, without any sign of scapular destabilization.The results suggest that botulinum toxin injection to spastic periscapular muscles can increase shoulder active ROM without causing scapular destabilization in patients with poststroke spastic scapular dyskinesia. PMID- 26266369 TI - Zolpidem Use Associated With Increased Risk of Pyogenic Liver Abscess: A Case Control Study in Taiwan. AB - The purpose of this study was to explore the association between zolpidem use and pyogenic liver abscess in Taiwan.This was a population-based case-control study using the database of the Taiwan National Health Insurance Program since 2000 to 2011. We identified 1325 patients aged 20 to 84 years with the first-attack of pyogenic liver abscess as the cases, and 5082 patients without pyogenic liver abscess matched with sex, age, comorbidities, and index year of hospitalization for pyogenic liver abscess as the controls. Patients whose last remaining 1 tablet for zolpidem was noted <=7 days before the date of admission for pyogenic liver abscess were defined as current use of zolpidem. Patients whose last remaining 1 tablet for zolpidem was noted >7 days before the date of admission for pyogenic liver abscess were defined as late use of zolpidem. Patients who never received 1 prescription for zolpidem were defined as never use of zolpidem. A multivariable unconditional logistic regression model was used to measure the odds ratio (OR) and 95% confidence interval (CI) to explore the association between zolpidem use and pyogenic liver abscess.After adjustment for possible confounding variables, the adjusted OR of pyogenic liver abscess was 3.89 for patients with current use of zolpidem (95% CI 2.89, 5.23), when compared with those with never use of zolpidem. The adjusted OR decreased to 0.85 for those with late use of zolpidem (95% CI 0.70, 1.03), but without statistical significance.Current use of zolpidem is associated with the increased risk of pyogenic liver abscess. Physicians should take the risk of pyogenic liver abscess into account when prescribing zolpidem. PMID- 26266370 TI - An Attempt to Evaluate Selected Aspects of "Bone-Fat Axis" Function in Healthy Individuals and Patients With Pancreatic Cancer. AB - Recently, much attention has been paid to a potential biochemical cross-talk between the metabolism of the adipose tissue (AT) and bone (marrow), termed "bone fat axis." We hypothesized that selected substances, participating in this "dialog," are associated with body mass and peripheral trafficking of bone marrow derived stem cells (BMSCs) in both healthy individuals and patients with obesity associated malignancies such as pancreatic adenocarcinoma.We performed an analysis of the systemic levels of selected substances involved in the regulation of bone (marrow) homeostasis (parathormone, calcitonin, osteopontin, osteonectin, stem cell factor [SCF], and fibroblast growth factor-23) in 35 generally healthy volunteers and 35 patients with pancreatic cancer. Results were correlated with the absolute number of circulating BMSCs and body mass values. Additionally, subcutaneous and visceral/omental AT levels of the aforementioned molecules were analyzed in lean and overweight/obese individuals.Intensified steady-state trafficking of only Lin-CD45 + CD133 + hematopoietic stem/progenitor cells was observed in overweight/obese individuals and this was associated with BMI values and elevated levels of both osteonectin and SCF, which also correlated with BMI. In comparison to healthy individuals, patients with cancer had significantly higher osteopontin levels and lower values of both osteonectin and osteonectin/osteopontin ratio. While no significant correlation was observed between BMI and the number of circulating BMSCs in patients with cancer, peripheral trafficking of CD34 + KDR + CD31 + CD45-endothelial progenitor cells and CD105 + STRO-1 + CD45-mesenchymal stem cells was associated with the osteonectin/osteopontin ratio, which also correlated with BMI (r = 0.52; P < 0.05). AT levels of the examined substances were similar to those measured in the plasma, except for osteonectin, which was about 10 times lower.Our study highlights the potential role of osteonectin, osteopontin, and SCF as communication signals between the bone (marrow) and AT in both healthy individuals and patients with pancreatic cancer. We postulate that these molecules may be overlooked biochemical players linking body mass and BMSCs with obesity-associated cancer development and/or progression in humans. PMID- 26266371 TI - Clinical Correlation Between Tumor Maximal Standardized Uptake Value in Metabolic Imaging and Metastatic Tumor Characteristics in Advanced Non-small Cell Lung Cancer. AB - This study aimed to elucidate whether the maximal standardized uptake value (SUVmax) of primary tumors in metabolic imaging correlated with pathological or metastatic characteristics and whether it was prognostic in stage IV nonsmall cell lung cancer (NSCLC).We retrospectively reviewed the medical records of 412 eligible patients between June 2007 and January 2013. All enrolled patients fulfilled the following criteria: they were newly diagnosed with stage IV NSCLC without any previous treatment and had undergone a systemic evaluation, including 18(F)-Fluoro-2-deoxyglucose positron emission tomography/computed tomography, to assess synchronous metastatic sites. Patient and tumor characteristics were analyzed, and clinical correlations between SUVmax and metastatic features were investigated.The median age of the study population was 65 years (range, 30-94), and 259 (62.9%) patients were male. The median SUVmax was statistically higher in males, in tumors with squamous cell histology, and in poorly differentiated tumors. Multivariate logistic regression analysis revealed that SUVmax >= 11.4 (top 30 percentiles) were significantly correlated with positive lymph node status (odds ratio [OR] 3.473), abdomen/pelvis metastasis (OR 1.949), and the absence of bone metastasis (OR 0.399) in the subgroup of nonsquamous NSCLC (n = 343). In Kaplan-Meier survival analysis, overall survival was significantly lower among cohorts with high SUVmax (>=11.4) than with low SUVmax (<11.4) (P < 0.001, median 7.4 months vs 12.1 months).The tumors with different SUVmax have distinctive metastatic and biological features in stage IV NSCLC. The underlying mechanisms of this unique metabolic biology need to be resolved in future studies. PMID- 26266372 TI - Reversible Severe Eosinophilic Endomyocardial Fibrosis During Pregnancy: A Case Report. AB - Idiopathic hypereosinophilic syndrome (HES) is a condition of unknown origin characterized by clinical manifestations attributable to eosinophilia and eosinophilic infiltration of tissues. Cardiac involvement is rare and threatening accounting for 33% to 43% of death in HES. Management of pregnant patients with HES is challenging and have rarely been reported, particularly in the setting of heart failure.We here report on the case of a 29-year-old woman with HES who developed severe endomyocardial fibrosis with heart failure during pregnancy. Outcome was favorable under treatment with prednisone and azathioprine.This case illustrates a favorable outcome of endomyocardial fibrosis during pregnancy. PMID- 26266373 TI - A Retrospective Study of Survivors of Endovascular Coiling for Posterior and Anterior Aneurysms: Medical and Patient Perspectives. AB - This article documents the longer-term medical and psychosocial outcomes of patients referred for endovascular coiling.There is limited research investigating outcome following endovascular coiling for posterior compared to anterior circulation aneurysms, and minimal understanding of how medical outcomes relate to patient experiences of treatment and quality of life.We studied a consecutive cohort of 80 patients referred Australia wide for endovascular coiling between 1995 and 2003 (49% posterior; 76% ruptured; 69% women, mean age 51.5 years). We used a mixed methods approach, assessing medical outcome with the Modified Rankin Scale (MRS) in 61 patients (76%), and health-related quality of life and psychosocial functioning using the EuroQol questionnaire and a qualitative semistructured interview in 49 patients (61%).Despite the high proportion of posterior aneurysms, the majority of patients (80%) showed good medical outcomes as indicated by regained independence of activities of daily living (MRS score <=3). Patients with unruptured aneurysms were significantly more likely to show good outcomes (P < 0.04), whereas aneurysm location (posterior, anterior, or mixed) showed no significant effect. In patients with good medical outcomes, greater functional disability was associated with neurological complications surrounding treatment (P < 0.05). Good outcomes correlated with higher EuroQol ratings (P < 0.001) and the experience of less change after treatment (P < 0.001), although psychosocial adjustment issues were reported by most of the patients, including those with no medical symptoms.These results support the long-term efficacy of endovascular coiling, particularly for posterior circulation aneurysms. They have implications for guiding clinicians and patients in their choice of treatment, as well as the provision of psychological counseling for patient adjustment issues posttreatment. PMID- 26266374 TI - Risk of Reverse Seroconversion of Hepatitis B Virus Surface Antigen in Rituximab Treated Non-Hodgkin Lymphoma Patients: A Large Cohort Retrospective Study. AB - Rituximab causes hepatitis B virus (HBV) reactivation in HBV surface antigen (HBsAg)-seronegative patients with CD20-positive B-cell non-Hodgkin lymphoma (CD20 NHL), especially for those seropositive to the antibody of core antigen (anti-HBc). Clinical hepatitis usually develops after reverse seroconversion of HBsAg (HBV-RS), indicated by the reappearance of HBsAg in serum. Because of the relatively high prevalence of anti-HBc seropositivity in unvaccinated HBsAg seronegative adults in an HBV hyperendemic area, we aimed to investigate additional factors influencing the development of rituximab-associated HBV RS.Between January 2000 and December 2010, unvaccinated HBsAg-seronegative adults with CD20 NHL who had received rituximab-containing therapy but not anti-HBV agents were enrolled. Patients with and without HBV-RS were compared in terms of clinical factors and treatments including the number of cycles of rituximab therapy, and transplantation. Competing risk regression was used to identify the factors associated with HBV-RS.For the 482 patients enrolled, the serological status of anti-HBc was available in 75.9%, with a seropositivity rate of 86.6%. At the last follow-up, a total of 33 (6.85%) patients had HBV-RS, with 95.8% anti HBc seropositive, 78.9% anti-HBs seropositive, and none anti-HCV seropositive. HBV-RS patients have received more cycles (>=6) and prolonged durations of rituximab therapy, and hematopoietic stem cell transplantation. The overall survival was not different between patients with and those without HBV-RS. At the time of HBV-RS, a total of 25 (78.1%) patients had hepatitis flare, especially when HBV-RS appeared during/after induction therapy (100%, 10 of 10). Three (9.1%) patients had fulminant hepatitis, resulting in death in 1 (3%) patient. A higher rituximab cycle intensity was associated with a higher rate of hepatitis flare at the time of HBV-RS. When death in the absence of HBV-RS was considered as the competing risk, the univariate and multivariate regression analyses showed that several factors were independently associated with the development of HBV RS, including anti-HCV seronegativity, histological subtype of posttransplant lymphoproliferative disorders, >=6 cycles of rituximab therapy, and succeeding hematopoietic stem cell transplantation.The findings of our study identify additional factors influencing the development of rituximab-associated HBV-RS in HBsAg-seronegative adults with CD20 NHL. PMID- 26266375 TI - Fetus in Fetu in the Scrotal Sac: Case Report and Literature Review. AB - Fetus in fetu (FIF) is a rare congenital anomaly. The most common site at which FIF occurs is the retroperitoneum. The mechanisms underlying the development of FIF have not been fully elucidated. The monozygotic twin theory postulates that FIF results from the unequal division of the totipotent cells of the blastocyst. However, the monozygotic twin theory does not explain all cases of FIF.Herein, we describe the clinical characteristics of a 20-day-old infant with scrotal sac swelling. Ultrasonography and computed tomography revealed the presence of a mass consistent with a FIF rather than a teratoma. Surgical removal and a subsequent pathological evaluation demonstrated that the anencephalic fetus exhibited limb buds adjacent to a palpable vertebral column, supporting the diagnosis of FIF. The infant had an uneventful recovery and was discharged on the fifth postoperative day. In the present report, the pathogenesis, presentation, diagnosis, and management of FIF, as well as new concepts emerging in this area of research, are discussed.Although the majority of cases of FIF may be diagnosed preoperatively, FIF should be distinguished from teratoma because the latter has substantial malignant potential. The recommended treatment for FIF is complete resection. To confirm the diagnosis of FIF, pathological examination, karyotyping, serologic marker assessment, and DNA restriction site mapping should be performed after removing the mass. Although FIF is thought to be a benign disorder, follow-up is necessary as a precaution against malignant recurrence, which has been described once. PMID- 26266376 TI - Effect of Intraoperative and Postoperative Infusion of Dexmedetomidine on the Quality of Postoperative Analgesia in Highly Nicotine-Dependent Patients After Thoracic Surgery: A CONSORT-Prospective, Randomized, Controlled Trial. AB - Smoking is one of the most common addictions in the world. Nicotine inhalation could increase the risk of cardiorespiratory diseases. However, the solution that improved postoperative analgesia for highly nicotine-dependent patients undergoing thoracic surgery has not been specifically addressed.This CONSORT prospective, randomized, double-blinded, controlled trial investigated the efficacy of combination of dexmedetomidine and sufentanil for highly nicotine (Fagerstrom test of nicotine dependence >=6)-dependent patients after thoracic surgery.One hundred seventy-four male patients who underwent thoracic surgery were screened between February 2014 and November 2014, and a total of forty-nine were excluded. One hundred thirty-two highly nicotine-dependent male patients who underwent thoracic surgery and received postoperative patient-controlled intravenous analgesia were divided into 3 groups after surgery in this double blind, randomized study: sufentanil (0.02 MUg/kg/h, Group S), sufentanil plus dexmedetomidine (0.02 MUg/kg/h each, Group D1), or sufentanil (0.02 MUg/kg/h) plus dexmedetomidine (0.04 MUg/kg/h) (Group D2). The patient-controlled analgesia (PCA) program was programmed to deliver a bolus dose of 2 ml, with background infusion of 2 ml/h and a lockout of 5 min, 4-hour limit of 40 ml, as our retrospective study. The primary outcome measure was the cumulative amount of self-administered sufentanil; the secondary outcome measures were pain intensity (numerical rating scale, NRS), level of sedation (LOS), Bruggrmann comfort scale (BCS), functional activity score (FAS), and concerning adverse effects.The amount of self-administered sufentanil were lower in group D2 compared with S and D1 groups during the 72 hours after surgery (P < 0.05), whereas the total dosage and dosage per body weight of sufentanil were significantly lower in D1 group than that of S group only at 4, 8, and 16 hours after surgery (P < 0.05). Compared with S group, the NRS scores at rest at 1, 4, and 8 hours after surgery and with coughing at 4, 8, 16, and 24 hours after surgery were significantly lower in D2 group (P < 0.05). However, compared with D1 group, the NRS scores both at rest and with coughing at 4 and 8 hours after surgery were significantly lower in D2 group (P < 0.05). The NRS scores both at rest and with coughing show that there were no significant differences between D1 group and S group at each time point after surgery (P > 0.05). LOS of group D2 was higher than S and D1 groups at 1 hour after surgery (P < 0.05), BCS of group D2 was higher than S and D1 groups at 4, 8, and 16 hours after surgery (P < 0.05), and FAS of group D2 was higher than S and D1 groups at 48 and 72 hours after surgery (P < 0.05). The number of rescue analgesia during 72 hours after surgery in D2 group was lower than S and D1 groups (P < 0.05). There were no significant differences among the 3 groups in terms of baseline clinical characteristics and postoperative adverse effects except for itching (P > 0.05).Among the tested patient-controlled analgesia options, the addition of dexmedetomidine (0.04 MUg/kg/h) and sufentanil (0.02 MUg/kg/h) showed better analgesic effect and greater patient satisfaction without other clinically relevant side effects for highly nicotine-dependent patients during the initial 72 hours after thoracic surgery. TRIAL REGISTRATION: chictr.org (ChiCTR-TRC-14004191). PMID- 26266377 TI - Does Tenascin have Clinical Implications in Pathological Grade of Glioma Patients?: A Systematic Meta-Analysis. AB - Tenascin (TN) is an extracellular oligomeric glycoprotein that participates in the adhesion of cells to extracellular matrixc (ECM). Studies have shown that the expression levels of TN are upregulated in a variety of cancers, including colon cancer, lung cancer, brain tumor, and breast cancer. However, the implications and utilities of TN in clinical grading and prognosis of glioma patients were seldom reported and the effects of its pathway are still unclear and controversial. Thus, it is essential to carry out a meta-analysis to draw a convincing conclusion.A literature search was carried out up to April 2015. Data was collected using a purpose-designed form including glioma's WHO grade, etc. Differences were expressed as odds ratios (ORs) or standard mean differences (SMDs) with 95% confidence intervals (CIs). Galbr figure, Cochran's Q test, and I test were all performed to judge the heterogeneity between included studies. To examine the stability of the pooled results, a sensitivity analysis was performed. Potential publication bias was assessed by visual inspection of funnel plot. As this meta-analysis, as a systematic review, does not involve animal experiments or direct human trials, there is no need to conduct special ethic review and the ethical approval is not necessary.In this meta-analysis, 8 eligible studies involving 456 patients were incorporated. Six studies with dichotomous data revealed TN overexpression in glioma tissues and/or surrounding neoplastic vessels was closely associated with high WHO grade (III + IV) (odds ratio 3.398, 95% confidence interval 1.933, 5.974; P = 0.000); three continuous data studies showed there were close statistical associations between TN and WHO grade (SMD -2.114, 95% CI -2.580, -1.649; P = 0.000) too. Sensitivity analysis indicated a statistically robust result. No publication bias was revealed.Our meta-analysis suggests that TN expression is potentially associated with higher WHO grade of gliomas. More evidences on the basis of the evidence-based medicine are needed to prove it. PMID- 26266378 TI - The Clinicopathologic and Prognostic Significance of Gross Classification on Solitary Hepatocellular Carcinoma After Hepatectomy. AB - The prevalence of hepatitis B virus (HBV) infection is extremely high in China. We aimed to investigate the clinicopathologic and prognostic significance of gross classification on solitary hepatocellular carcinoma (HCC) after hepatectomy.A total of 144 patients with solitary HCC who underwent hepatectomy were identified retrospectively. Based on the gross appearance, the tumors were divided into single nodular (SN), single nodular with extranodular growth (SNEG), confluent multinodular (CMN), and infiltrative types. Clinicopathologic variables and survival information were compared among patients with those 4 types.The 144 tumors composed of 25 SN, 34 SNEG, 33 CMN, and 52 infiltrative types. The serum alpha-fetoprotein (AFP) level and HBV infection rate of infiltrative type were significantly higher than other 3 types. The disease-free and overall survival times of infiltrative type were significantly shorter than other 3 types. Univariate and multivariate analysis showed that gross classification, microvascular invasion, and T stage were independent risk factors.In Chinese patients with solitary HCC, the infiltrative type accounted for a much higher proportion compared with other regions of the world. Infiltrative HCC had higher serum AFP level, HBV infection, and microvascular invasion rates with poorer prognosis compared with other 3 types. PMID- 26266379 TI - A Taiwanese Nationwide Cohort Study Shows Interferon-Based Therapy for Chronic Hepatitis C Reduces the Risk of Chronic Kidney Disease. AB - Hepatitis C virus (HCV) infection is a risk factor for chronic kidney disease (CKD). However, it remains unclear whether interferon-based therapy (IBT) for HCV was associated with reduced risk of CKD.From the Taiwan National Health Insurance Research Database, we identified 919 patients who received 3 months or more of IBT as our treated cohort. This cohort was propensity score-matched 1:4 with 3676 controls who had never received IBT for HCV infection (untreated cohort). Cumulative incidences of and hazard ratios (HRs) for CKD were calculated after adjusting for competing mortality.In the matched HCV cohort, the risk of CKD was significantly lower in the treated cohort (7-year cumulative incidence, 2.6%; 95% confidence interval [CI], 0.7%-6.9%) than in the untreated cohort (4%; 95% CI, 3.5%-5.2%) (P < 0.001), with an adjusted HR of 0.42 (95% CI, 0.20-0.92; P = 0.03). The results also held in the overall HCV cohort. The number needed to treat for 1 fewer CKD at 7 years was 58. The reduced risk of CKD was greatest (0.35; 0.14-0.87; P = 0.024) in HCV-infected patients who received 6 months or more of IBT. Multivariable stratified analysis verified that greater risk reduction of CKD was present in HCV-infected patients with hyperlipidemia, diabetes, hypertension, and those without coronary heart disease.In conclusion, IBT, especially for 6 or more months, is associated with reduced risk of CKD in HCV-infected patients. Hyperlipidemia, diabetes, hypertension, and coronary heart disease can modify this association. PMID- 26266380 TI - Examining the Association Between Quadriceps Strength and Cognitive Performance in the Elderly. AB - Emerging evidences showed impaired muscle strength was prevalent in older adults with mild cognition impairment or dementia. However, little was known about the role of quadriceps strength in the cognition decline among older population. The objective of our study was to investigate the relation between quadriceps strength and cognitive performance. Using data from the National Health and Nutrition Examination Survey (1999-2002), a total of 1799 participants aged >=60 years were enrolled in the study. Every subject completed a household interview, digit symbol substitution test (DSST), physical performances, and a questionnaire regarding personal health. Estimation of relationship between quadriceps strength and cognition was using multiple linear regression and quartile-based analysis with an extended-model approach for covariates adjustment. In a model adjusted for demographics, chronic diseases, health behaviors, and levels of folate and vitamin B12, the level of quadriceps strength was significantly associated with the scores of DSST. The beta coefficient interpreted as change of DSST scores for each Newton increment in quadriceps strength comparing participants in the highest quartile of quadriceps strength to those in the lowest quartile was 5.003 (95% confidence interval, 2.725-7.281, P < 0.001). The trends of incremental DSST score across increasing quartiles of quadriceps strength were statistically significant (all P for trend <0.001). Higher quadriceps strength was associated with better cognitive performance. PMID- 26266381 TI - Recurrence Risk Factors Analysis for Stage I Non-small Cell Lung Cancer. AB - Lung cancer is the leading cause of cancer-related death worldwide. Even early stage patients might encounter disease recurrence with relative high risk. Effective postoperative therapy is based on an accurate assessment of treatment failure after surgery. The aim of this study is to construct a disease-free survival (DFS) prediction model and stratify patients into different risk score groups.A total of 356 pathological stage I patients (7th American Joint Committee on Cancer) who underwent lung resection from January 2005 through June 2011 were retrospectively reviewed. Of these patients, 63 patients were eliminated for this study. A total of 293 p-stage I patients were included for further univariate and multivariate analysis. Clinical, surgical, and pathological factors associated with high risk of recurrence were analyzed, including age, gender, smoking status, additional primary malignancy (APM), operation method, histology, visceral pleural invasion, angiolymphatic invasion, tumor necrosis, and tumor size.Of the 293 p-stage I non-small cell lung cancer (NSCLC) patients examined, 143 were female and 150 were male, with a mean age of 62.8-years old (range: 25 83-years old). The 5-year DFS and overall survival rates after surgery were 58.9% and 75.3%, respectively. On multivariate analysis, current smoker (hazards ratio [HR]: 1.63), APM (HR: 1.86), tumor size (HR: 1.54, 2.03), nonanatomic resections (HR: 1.81), adenocarcinoma histology (HR: 2.07), visceral pleural invasion (HR: 1.54), and angiolymphatic invasion (HR: 1.53) were found to be associated with a higher risk of tumor recurrence. The final model showed a fair discrimination ability (C-statistic = 0.68). According to the difference risk group, we found patients with intermediate or higher risk group had a higher distal relapse tendency as compared with low risk group (P = 0.016, odds ratio: 3.31, 95% confidence interval: 1.21-9.03).Greater than 30% of disease recurrences occurred after surgery for stage I NSCLC patients. That is why we try to establish an effective DFS predicting model based on clinical, pathological, and surgical covariates. However, our initial results still need to be validated and refined into greater population for better application in clinical use. PMID- 26266382 TI - Pars Plana Vitrectomy and Evisceration Resulting in Death Due to Misdiagnosis of Retinoblastoma in Children: A Review of 3 Cases. AB - Retinoblastoma is a curable intraocular malignancy in children. However, in clinical practice, retinoblastoma can sometimes be misdiagnosed and mismanaged, leading to extraocular extension and even death. In this report, a series of 3 cases are related that emphasize the conditions and consequences resulting from misdiagnosis and mismanagement of retinoblastoma. The clinical features, imaging findings, histopatholigical examination, and management in 3 case reports of children with misdiagnosed retinoblastoma are presented. Two of the cases received pars plana vitrectomy after being misdiagnosed with Coats disease or ocular blunt trauma, whereas the third case received evisceration after being misdiagnosed with suppurative endophthalmitis. When the diagnosis of retinoblastoma had been confirmed after a second surgery was performed in our hospital, only 2 of the cases received adjuvant orbital radiotherapy. All 3 cases died of systemic tumor metastases. Intraocular surgical procedures should be avoided in any equivocal case until the possibility of latent retinoblastoma is eliminated.We strongly recommend that early enucleation be executed as soon as possible followed by postoperative adjuvant therapy under conditions wherein an intraocular surgery was inadvertently performed in an eye with retinoblastoma. PMID- 26266383 TI - Durability of Nucleos(t)ide Analogues Treatment in Patients With Chronic Hepatitis B. AB - Long-term nucleos(t)ide analogues (NUCs) treatment is usually required for patients with chronic hepatitis B (CHB). However, whether discontinuation of NUCs is possible in selected patients remains debated. The aim of this study was to assess the durability of NUCs and predictors of sustained response after cessation of NUCs.Ninety-three CHB patients (29 HBeAg-positive and 64 HBeAg negative) from 2 medical centers in Taiwan with discontinuation of NUCs after a median of 3 years' treatment were retrospectively reviewed. Fifteen (51.7%) HBeAg positive and 57 (89.1%) HBeAg-negative patients achieved APASL treatment endpoints. Virological relapse (VR) and clinical relapse (CR) were defined according to APASL guidelines.Achieving APASL endpoint was associated with longer median time to CR in HBeAg-positive patients, but not in HBeAg-negative cases. The cumulative 1-year VR and CR rates were 55.3% and 14.4% in HBeAg-positive patients, and 77.7% and 41.9% in HBeAg-negative patients, respectively. In HBeAg negative patients, baseline HBV DNA >10 IU/mL was the only predictor of VR (hazard ratio [HR] = 2.277, P = 0.019) and CR (HR = 3.378, P = 0.014). HBsAg >200 IU/mL at the end of treatment (EOT) was associated with CR (HR = 3.573, P = 0.023) in patients developing VR. HBeAg-negative patients with low baseline viral loads and low HBsAg levels at EOT had minimal risk of CR after achieving APASL treatment endpoint (P = 0.016).The VR rate is high, but the risk of CR is low within 1 year with consolidation treatment after HBeAg seroconversion. Longer consolidation treatment to reduce the risk of VR should be considered in HBeAg positive patients. As high risk of VR and CR, cessation of NUCs therapy could be considered only in selected HBeAg-negative patients. PMID- 26266384 TI - Hospital Blood Transfusion Patterns During Major Noncardiac Surgery and Surgical Mortality. AB - We retrospectively examined intraoperative blood transfusion patterns at US veteran's hospitals through description of national patterns of intraoperative blood transfusion by indication for transfusion in the elderly; assessment of temporal trends in the use of intraoperative blood transfusion; and relationship of institutional use of intraoperative blood transfusion to hospital 30-day risk adjusted postoperative mortality rates.Limited data exist on the pattern of intraoperative blood transfusion by indication for transfusion at the hospital level, and the relationship between intraoperative transfusion rates and institutional surgical outcomes.Using the Department of Veterans Affairs Surgical Quality Improvement Program database, we assigned 424,015 major noncardiac operations among elderly patients (>=65 years) in 117 veteran's hospitals, from 1997 to 2009, into groups based on indication for intraoperative blood transfusion according to literature and clinical guidelines. We then examined institutional variations and temporal trends in surgical blood use based on these indications, and the relationship between these institutional patterns of transfusion and 30-day postoperative mortality.Intraoperative transfusion occurred in 38,056/424,015 operations (9.0%). Among the 64,390 operations with an indication for transfusion, there was wide variation (median: 49.9%, range: 8.7% 76.2%) in hospital transfusion rates, a yearly decline in transfusion rates (average 1.0%/y), and an inverse relationship between hospital intraoperative transfusion rates and hospital 30-day risk-adjusted mortality (adjusted mortality of 9.8 +/- 2.8% vs 8.3 +/- 2.1% for lowest and highest tertiles of hospital transfusion rates, respectively, P = 0.02). In contrast, for the 225,782 operations with no indication for transfusion, there was little variation in hospital transfusion rates (median 0.7%, range: 0%-3.4%), no meaningful temporal change in transfusion (average 0.0%/y), and similar risk-adjusted 30-day mortality across all tertiles of hospital transfusion rates.Among patients >=65 years with an indication for intraoperative transfusion, intraoperative transfusion patterns varied widely across hospitals and declined through the 1997 to 2009 study period. Hospitals with higher transfusion rates in these patients have lower risk-adjusted 30-day postoperative mortality rates. PMID- 26266385 TI - Improvement of Short-Term Outcomes for High-Risk Bleeding Peptic Ulcers With Addition of Argon Plasma Coagulation Following Endoscopic Injection Therapy: A Randomized Controlled Trial. AB - A second endoscopic method together with injection therapy is recommended to treat high-risk bleeding peptic ulcers. This study investigated whether additional argon plasma coagulation (APC) treatment could influence hemostatic efficacy following endoscopic injection therapy to treat high-risk bleeding ulcers.From October 2010 to January 2012, eligible patients with high-risk bleeding ulcers were admitted to our hospital. They prospectively randomly underwent either APC therapy along with distilled water injection or distilled water injection alone. Episodes of rebleeding were retreated with endoscopic combination therapy. Patients in whom retreatment was ineffective underwent emergency surgery or transarterial embolization (TAE).A total of 116 enrolled patients were analyzed. The hemostatic efficacy in 58 patients treated with APC along with distilled water injection was compared with that in 58 patients treated with distilled water injection alone. The 2 treatment groups were similar with respect to all baseline characteristics. Initial hemostasis was accomplished in 56 patients treated with combined therapy, and 55 patients treated with distilled water injection therapy (97% vs 95%, P = 0.648). Bleeding recurred in 2 patients treated with combined therapy, and 9 patients treated with distilled water injection (3.6% vs 16%, P = 0.029). Treatment method was the only independent prognostic factor for recurrent bleeding (odds ratio 0.17; 95% confidence interval 0.03-0.84; P = 0.029). The 2 groups did not differ significantly in hospital stay, TAE, surgery, and mortality.Endoscopic therapy with APC following distilled water injection is more effective than distilled water injection alone for preventing rebleeding of peptic ulcer. PMID- 26266386 TI - Dexmedetomidine in Postoperative Analgesia in Patients Undergoing Hysterectomy: A CONSORT-Prospective, Randomized, Controlled Trial. AB - Both dexmedetomidine and sufentanil modulate spinal analgesia by different mechanisms, and yet no human studies are available on their combination for analgesia during the first 72 hours after abdominal hysterectomy.This CONSORT prospective, randomized, double-blinded, controlled trial sought to evaluate the safety and efficacy of the combination of dexmedetomidine and sufentanil in intravenous patient-controlled analgesia (PCA) for 72 hours after abdominal hysterectomy.Ninety women undergoing total abdominal hysterectomy were divided into 3 equal groups that received sufentanil (Group C; 0.02 MUg/kg/h), sufentanil plus dexmedetomidine (Group D1; 0.02 MUg/kg/h, each), or sufentanil (0.02 MUg/kg/h) plus dexmedetomidine (0.05 MUg/kg/h) (Group D2) for 72 hours after surgery in this double-blinded, randomized study. The primary outcome measure was the postoperative sufentanil consumption, whereas the secondary outcome measures were pain intensity (visual analogue scale), requirement of narcotic drugs during the operation, level of sedation, Bruggrmann comfort scale, and concerning adverse effects.The postoperative sufentanil consumption was significantly lower in Groups D1 and D2 than in Group C during the observation period (P < 0.05), but lower in Group D2 than in Group D1 at 24, 48, and 72 hours after surgery (P < 0.05). The heart rate after intubation and incision was lower in Groups D1 and D2 than in Group C (P < 0.05). On arrival at the recovery room, Groups D1 and D2 had lower mean blood pressure than Group C (P < 0.05). The intraoperative requirement of sevoflurane was 30% lesser in Groups D1 and D2 than in Group C. The sedation levels were greater in Groups D1 and D2 during the first hour (P < 0.05). Compared with Groups C and D1, Group D2 showed lower levels of the overall incidence of nausea and vomiting (P < 0.05).Among the tested PCA options, the addition of dexmedetomidine (0.05 MUg/kg/h) and sufentanil (0.02 MUg/kg/h) showed better analgesic effect and greater patient satisfaction without other clinically relevant side effects for patients undergoing hysterectomy during the first 72 hours after abdominal hysterectomy. PMID- 26266387 TI - Comparative Effects of Dexmedetomidine and Propofol on US-Guided Radiofrequency Ablation of Hepatic Neoplasm Under Monitored Anesthesia Care: A Randomized Controlled Study. AB - Percutaneous radiofrequency ablation (RFA) is a useful and safe procedure for treating hepatic neoplasm. However, liver RFA causes severe pain, which thereby increases the demand for monitored anesthesia care (MAC). Here, we compared the efficacy and safety of propofol and dexmedetomidine, which are commonly administered during MAC when performing RFA to assess hepatic neoplasm.In this randomized controlled trial, 40 patients were randomly allocated to 2 groups for elective RFA. Patients received either dexmedetomidine (group D) or propofol (group P). Both groups received the continuous infusion of remifentanil for pain control. The primary outcomes were opioid consumption and differences in partial pressure of arterial carbon dioxide (PaCO2) between pre- and postprocedure RFA. In addition, hemodynamic parameters, patient satisfaction, and interventional radiologist satisfaction were determined.There were significant differences in opioid consumption (50.1 +/- 16.8 ng/kg/min [group D] vs 71.2 +/- 18.7 ng/kg/min [group P]; P = 0.001) and delta PaCO2 (10.4 +/- 6.4 mm Hg vs 17.2 +/- 9.2 mm Hg, respectively; P = 0.016). Moreover, respiratory rates were significantly different between groups during RFA (P < 0.001). However, blood pressure and heart rate did not significantly change during RFA. Neither patient nor interventional radiologist satisfaction was significantly different between groups.Dexmedetomidine provides better respiratory stability and reduces opioid consumption in comparison with propofol when administered under MAC when performing RFA for hepatic neoplasm. PMID- 26266388 TI - Systematic Review and Meta-Analysis on the Influence of Surgeon Specialization on Outcomes Following Appendicectomy in Children. AB - The aim of this study is to assess the influence of surgeon specialization on outcomes following appendicectomy in children.General surgeons and pediatric surgeons manage appendicitis in children; however, the influence of subspecialization on outcomes remains unclear.Two authors searched Medline and Embase to identify relevant studies. Eligible studies were comparative and provided data on children who had appendicectomy while under the care of general or pediatric surgical teams. Two authors initially screened titles and abstracts and then full text manuscripts were evaluated. Data were extracted by 2 authors using an electronic spreadsheet. Pooled risk ratios and pooled mean differences were used in analyses.We identified 9 relevant studies involving 50,963 children who were managed by general surgery teams and 15,032 children who were managed by pediatric surgery teams. A normal appendix was removed in 4660/48,105 children treated by general surgery units and in 889/14,760 children treated by pediatric units (pooled risk ratio 1.79; 95% confidence interval [CI] 1.26-2.54; P = 0.001). Children managed in general units had shorter mean hospital stays compared with children managed in pediatric units (pooled mean difference -0.70 days; 95%CI -1.09 to -0.30; P = 0.0005). There were no significant differences regarding wound infections, intra-abdominal abscesses, readmissions, or mortality.We found that children who were managed by specialized pediatric surgery teams had lower rates of negative appendicectomy although mean length of stay was longer. Our article is based upon a group of heterogeneous and mostly retrospective studies and therefore there is little external validity. Further studies are needed. PMID- 26266389 TI - Understanding the Racial and Ethnic Differences in Cost and Mortality Among Advanced Stage Prostate Cancer Patients (STROBE). AB - The aims of the study were to understand the racial/ethnic differences in cost of care and mortality in Medicare elderly with advanced stage prostate cancer.This retrospective, observational study used SEER-Medicare data. Cohort consisted of 10,509 men aged 66 or older and diagnosed with advanced-stage prostate cancer between 2001and 2004. The cohort was followed retrospectively up to 2009. Racial/ethnic variation in cost was analyzed using 2 part-models and quantile regression. Step-wise GLM log-link and Cox regression was used to study the association between race/ethnicity and cost and mortality. Propensity score approach was used to minimize selection bias.Pattern of cost and mortality varies between racial/ethnic groups. Compared with other racial/ethnic groups, non Hispanic white patients had higher unadjusted costs in treatment and follow-up phases. Quintile regression results indicated that in treatment phase, Hispanics had higher costs in the 95th quantile and non-Hispanic blacks had lower cost in the 95th quantile, compared with non-Hispanic white men. In terminal phase non Hispanic blacks and Hispanics had higher cost. After controlling for treatment, all-cause and prostate cancer-specific mortality was not significant for non Hispanic black men, compared with non-Hispanic white men. However, for Asians, mortality remained significantly lower compared with non-Hispanic white men.In conclusion, relationship between race/ethnicity, cost of care, and mortality is intricate. For non-Hispanic black men, disparity in mortality can be attributed to treatment differences. To reduce racial/ethnic disparities in prostate cancer care and outcomes, tailored policies to address underuse, overuse, and misuse of treatment and health services are necessary. PMID- 26266390 TI - Increasing Receipt of High-Tech/High-Cost Imaging and Its Determinants in the Last Month of Taiwanese Patients With Metastatic Cancer, 2001-2010: A Retrospective Cohort Study. AB - One strategy for controlling the skyrocketing costs of cancer care may be to target high-tech/high-cost imaging at the end of life (EOL). This population based study investigated receipt of high-tech/high-cost imaging and its determinants for Taiwanese patients with metastatic cancer in their last month of life.Individual patient-level data were linked with encrypted identification numbers from computerized administrative data in Taiwan, that is, the National Register of Deaths Database, Cancer Registration System database, and National Health Insurance claims datasets, Database of Medical Care Institutions Status, and national census statistics (population/household income). We identified receipt of computerized tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and radionuclide bone scans (BSs) for 236,911 Taiwanese cancer decedents with metastatic disease, 2001 to 2010. Associations of patient, physician, hospital, and regional factors with receiving CT, MRI, and bone scan in the last month of life were evaluated by multilevel generalized linear-mixed models.Over one-third (average [range]: 36.11% [33.07%-37.31%]) of patients with metastatic cancer received at least 1 high-tech/high-cost imaging modality in their last month (usage rates for CT, MRI, PET, and BS were 31.05%, 5.81%, 0.25%, and 8.15%, respectively). In 2001 to 2010, trends of receipt increased for CT (27.96-32.22%), MRI (4.34-6.70%), and PET (0.00-0.62%), but decreased for BS (9.47-6.57%). Facilitative determinants with consistent trends for at least 2 high-tech/high-cost imaging modalities were male gender, younger age, married, rural residence, lung cancer diagnosis, dying within 1 to 2 years of diagnosis, not under medical oncology care, and receiving care at a teaching hospital with a larger volume of terminally ill cancer patients and greater EOL care intensity. Undergoing high-tech/high-cost imaging at EOL generally was not associated with regional characteristics, healthcare resources, and EOL care intensity.To more effectively use high-tech/high-cost imaging at EOL, clinical and financial interventions should target nonmedical oncologists/hematologists affiliated with teaching hospitals that tend to aggressively treat high volumes of terminally ill cancer patients, thereby avoiding unnecessary EOL care spending and transforming healthcare systems into affordable high-quality cancer care delivery systems. PMID- 26266391 TI - Individuals With Type 2 Diabetes Mellitus Are at an Increased Risk of Gout But This Is Not Due to Diabetes: A Population-Based Cohort Study. AB - The relationship between type 2 diabetes and gout is complex. The objective of this study was to understand the role of diabetes itself and its comorbidities within the association between type 2 diabetes and gout.We conducted a retrospective cohort study using the UK Clinical Practice Research Datalink (CPRD) GOLD. Persons with type 2 diabetes were identified as persons on a noninsulin antidiabetic drug (NIAD) between 2004 and 2012, and were matched to 1 control based on age, sex, and general practice. We estimated gout risk in NIAD users using Cox regression analysis. All analyses were stratified for sex.In total, 221,117 NIAD users were identified. NIAD users had an increased risk of gout (hazard ratio (HR) 1.48; 95% CI 1.41-1.54). This association was stronger in women (HR 2.23; 95% CI 2.07-2.41) compared with men (HR 1.19; 95% CI 1.13-1.26). After adjustments for BMI, eGFR, hypertension, renal transplantation, diuretics, statins, low-dose aspirin, ciclosporin, and tacrolimus, the risk disappeared in women (HR 1.01; 95% CI 0.92-1.11) and reversed in men (HR 0.61; 95% CI 0.58-0.66) (P for interaction <0.001). When stratifying gout risk according to HbA1c in male and female NIAD users, we found an inverse association between raising HbA1c and incident gout in men only. Further adjustment gave similar results.Individuals with type 2 diabetes are at increased risk of gout. This is not due to diabetes itself, but to the comorbid conditions. Diabetes itself is apparently associated with a decreased risk of gout, especially in men. PMID- 26266392 TI - Interrelationships Between Ki67, HER2/neu, p53, ER, and PR Status and Their Associations With Tumor Grade and Lymph Node Involvement in Breast Carcinoma Subtypes: Retrospective-Observational Analytical Study. AB - Various predictive and prognostic factors could affect breast carcinoma behavior, but to date no definitive correlation has been established between them and breast carcinoma subtypes. The present study was conducted to examine the interrelationships of these predictive and prognostic factors as well as their effects on breast carcinoma subtypes.The archives of all patients with breast carcinoma (from 2008 to 2014) were studied. Patients' data were extracted using a checklist that included age, histology type, size and grade of tumor, lymph node involvement, estrogen receptor (ER) and progesterone receptor (PR) status, along with the overexpression of human epidermal growth factor receptor (HER2/neu) and the rate of Ki67 and p53 mutations. All data were analyzed by SPSS-17 software with chi and Fisher exact tests, as well as the least significant difference pairwise comparison test.A total of 566 patients' records were included in this study. The mean age of patients was 50 +/- 12.9 with an age range of 17 to 98 years. A meaningful correlation was found between age and the type of tumor (P = 0.001). Infiltrating lobular carcinoma had a higher ER positivity between groups (85.7%), whereas noninvasive carcinomas had a higher PR positivity (67%). In addition, a meaningful correlation was detected between the type and grade of tumor (P = 0.001). No meaningful relationship was observed between the type of tumor and HER2/neu overexpression and number of lymph nodes involved. Between the groups, medullary carcinoma had the highest Ki67 index (P = 0.007). Meaningful correlation was found between the grade of tumor and lymph node involvement (P = 0.005) and also with HER2/neu overexpression (P = 0.002). Higher grades had greater positivity in Ki67 index and p53 mutation rates (P = 0.002, P = 0.01). HER2/neu positive tumors had a higher Ki67 index (P = 0.03).Higher Ki67 index tumors showed more HER2/neu overexpression, larger size, and more lymph node involvement compared with other types and maybe considered aggressive. Moreover, in young patients with breast carcinoma, the rates of Ki67 with the overexpression of HER2/neu and p53 mutations are higher, and it shows a more aggressive behavior than other tumors assessed in this age group. PMID- 26266393 TI - Rituximab for the Treatment of IgG4-Related Tubulointerstitial Nephritis: Case Report and Review of the Literature. AB - Immunoglobulin type gamma 4 (IgG4)-related disease is a relatively newly described clinical entity characterized by a distinctive histopathological appearance, increased numbers of IgG4 positive plasma cells and often, but not always, elevated serum IgG4 concentrations. The most common renal manifestation of IgG4-related disease is tubulointerstitial nephritis marked with proteinuria, hematuria, decreased kidney function, hypocomplementemia, and radiologic abnormalities. Renal biopsy characteristics include dense lymphoplasmacytic tubulointerstitial nephritis that stains for IgG4, storiform fibrosis, and immune complex deposition in the interstitium and along tubule basement membranes. Treatment traditionally consists of prolonged glucocorticoids but cases refractory to glucocorticoids have been reported.We report a case of a 58-year old Caucasian man who presented with fatigue, 50 pound weight loss, dyspnea, lymphadenopathy, and nephromegaly. The patient was first misdiagnosed as chronic interstitial nephritis secondary to renal sarcoid and was treated with repeated doses of prednisone. On his third relapse, he underwent a repeat renal biopsy and a diagnosis of IgG4-tubulointerstitial nephritis was confirmed. He was refractory to treatment with prednisone. The patient received Rituximab and had prompt sustained improvement in renal function. At 1 year post Rituximab treatment, his serum creatinine remains at baseline and imaging study revealed reduction in his kidney size.This is the first case report using Rituximab as a steroid sparing option for refractory IgG4-tubulointerstitial nephritis. More information is needed on the long-term effects of using of B-cell depleting agents for glucocorticoid resistant IgG4-tubulointerstitial nephritis. PMID- 26266394 TI - Frequency-Specific Alterations of Local Synchronization in Idiopathic Generalized Epilepsy. AB - Recurrently and abnormally hypersynchronous discharge is a striking feature of idiopathic generalized epilepsy (IGE). Resting-state functional magnetic resonance imaging has revealed aberrant spontaneous brain synchronization, predominately in low-frequency range (<0.1 Hz), in individuals with IGE. Little is known, however, about these changes in local synchronization across different frequency bands. We examined alterations to frequency-specific local synchronization in terms of spontaneous blood oxygen level-dependent (BOLD) fluctuations across 5 bands, spanning 0 to 0.25 Hz. Specifically, we compared brain activity in a large cohort of IGE patients (n = 86) to age- and sex-matched normal controls (n = 86). IGE patients showed decreased local synchronization in low frequency (<0.073 Hz), primarily in the default mode network (DMN). IGE patients also exhibited increased local synchronization in high-frequency (>0.073 Hz) in a "conscious perception network," which is anchored by the pregenual and dorsal anterior cingulate cortex, as well as the bilateral insular cortices, possibly contributing to impaired consciousness. Furthermore, we found frequency specific alternating local synchronization in the posterior portion of the DMN relative to the anterior part, suggesting an interaction between the disease and frequency bands. Importantly, the aberrant high-frequency local synchronization in the middle cingulate cortex was associated with disease duration, thus linking BOLD frequency changes to disease severity. These findings provide an overview of frequency-specific local synchronization of BOLD fluctuations, and may be helpful in uncovering abnormal synchronous neuronal activity in patients with IGE at specific frequency bands. PMID- 26266395 TI - Unintentional Injuries in Preschool Age Children: Is There a Correlation With Parenting Style and Parental Attention Deficit and Hyperactivity Symptoms. AB - Unintentional injuries are the leading cause of death among children. Previous research has shown that most of the injuries occur in and around the home. Therefore, parents have a key role in the occurrence and prevention of injuries. In this study, we examined the relationship among home injuries to children and parental attention deficit hyperactivity disorder (ADHD) symptoms, parental attitudes, and children's behavioral problems.Forty children who were admitted to the emergency department because of home injuries constitute the study group. The control group also consisted of 40 children, who were admitted for mild throat infections. The parents filled out questionnaires assessing parental ADHD, child behavioral problems, and parenting attitudes.Scores were significantly higher for both internalizing disorders and externalizing disorders in study groups. We also found that ADHD symptoms were significantly higher among fathers of injured children compared with fathers of control groups. Democratic parenting was also found to correlate with higher numbers of injuries.Parenting style, as well as the psychopathology of both the parents and children, is important factors in children's injuries. A child psychiatrist visit following an emergency procedure may help to prevent further unintentional injuries to the child. PMID- 26266396 TI - Intrathoracic Benign Goiter Imaged by 18F-FDG-PET: A Case Report. AB - A 55-year-old woman was referred for a suspicion of mediastinal tumor through plain X-ray photography (X-P). Magnetic resonance imaging (MRI) revealed a 3 cm diameter tumor which seemed to connect to the thyroid and projected into the mediastinum. A fine needle aspiration biopsy was tried but could not reach a conclusive diagnosis. Thereby, fluorine-18-fluorodeoxyglucose positron emission tomography (F-FDG-PET) was performed and a high accumulation was revealed with standardized uptake value (SUV) of 3.8. Thus, the right lobe excision procedure was enforced. The obtained tumor was continuous to the right lobe as expected. Microscopically, the encapsulated tumor consisted of atypical large-sized follicles without malignant characteristics. Thus, histological diagnosis was follicular thyroid adenoma.Thus, follicular adenoma of thyroid could present negative iodine-123-radioisotope (I-RI) uptake and positive F-FDG-PET accumulation. PMID- 26266397 TI - Cardiac Dextroversion after Right Lower Lobe Lobectomy. PMID- 26266398 TI - In Situ Synthesis of Catalytic Active Au Nanoparticles onto Gibbsite-Polydopamine Core-Shell Nanoplates. AB - We report a facile method to synthesize anisotropic platelike gibbsite-polymer core-shell particles. Dopamine is self-polymerized on the surface of gibbsite nanoplates and forms a homogeneous layer on it. Transmission electron microscopy characterization of the resulting latexes demonstrates the formation of well defined platelike core-shell particles. Reaction time and ultrasonification are found to be important factors to control the thickness of the polymer shell and avoid aggregation. Good control over the platelike morphology and 100% encapsulation efficiency have been achieved via this novel route. The resulting well-defined gibbsite-polydamine (G-PDA) core-shell nanoplates show excellent colloidal stability and can form opal-like columnar crystal with iridescent Bragg reflection after modest centrifugation. In addition, G-PDA core-shell nanoplates can serve both as reductant and stabilizer for the generation of Au nanoparticles (NPs) in situ. Au NPs with tunable size have been formed on the G-PDA particle surface, which show efficient catalytic activity for the reduction of 4 nitrophenol and Rhodamine B (RhB) in the presence of borohydride. Such nanocatalysts can be easily deposited on silicon substrate by spin-coating due to the large contact area of platelike G-PDA particles and the strong adhesive behavior of the PDA layer. The substrate-deposited nanocatalyst can be easily recycled which show excellent reusability for the reduction of RhB. PMID- 26266399 TI - A smart device for label-free and real-time detection of gene point mutations based on the high dark phase contrast of vapor condensation. AB - A smart device for label-free and real-time detection of gene point mutation related diseases was developed based on the high dark phase contrast of vapor condensation. The main components of the device included a Peltier cooler and a mini PC board for image processing. Heat from the hot side of the Peltier cooler causes the fluid in a copper chamber to evaporate, and the vapor condenses on the surface of a microarray chip placed on the cold side of the cooler. The high dark phase contrast of vapor condensation relative to the analytes on the microarray chip was explored. Combined with rolling circle amplification, the device visualizes less-to-more hydrophilic transitions caused by gene trapping and DNA amplification. A lung cancer gene point mutation was analysed, proving the high selectivity and multiplex analysis capability of this low-cost device. PMID- 26266401 TI - Intense pulsed light, near infrared pulsed light, and fractional laser combination therapy for skin rejuvenation in Asian subjects: a prospective multi center study in China. AB - Ablative skin rejuvenation therapies have limitations for Asian people, including post-inflammatory hyperpigmentation and long down time. Non-ablative lasers are safer but have limited efficacy. This study is to investigate the safety and efficacy of a combination therapy consisting of intense pulsed light (IPL), near infrared (NIR) light, and fractional erbium YAG (Er:YAG) laser for skin rejuvenation in Asian people. This study recruited 113 subjects from six sites in China. Subjects were randomly assigned to a full-face group, who received combination therapy, and split-face groups, in which one half of the face received combination therapy and the other half received IPL monotherapy. Each subject received five treatment sessions during a period of 90 days. Subjects were followed up at 1 and 3 months post last treatment. Three months after last treatment, the full-face group (n = 57) had a global improvement rate of 29 % and 29 % for wrinkles, 32 % for skin texture, 33 % for pigment spots, 28 % for pore size, respectively. For patients in the split-face groups (n = 54), monotherapy side had a global improvement rate of 23 % and 20 % for wrinkles, 27 % for skin texture, 25 % for pigment spots, 25 % for pore size, respectively. Both combination therapy and monotherapy resulted in significant improvements at the follow-up visits compared to baseline (P < 0.001). Combination therapy showed significantly greater improvements compared to monotherapy at two follow-up visits (P < 0.05). Combination therapy is a safe and more effective strategy than IPL monotherapy for skin rejuvenation in Asian people. PMID- 26266400 TI - Daily and annual cycles in thermoregulatory behaviour and cardio-respiratory physiology of black and white tegu lizards. AB - This study was designed to determine the manner in which metabolism is suppressed during dormancy in black and white tegu lizards (Tupinambis merianae). To this end, heart rate (fH), respiration rate (fR), and deep body temperature (Tb) were continuously monitored in outdoor enclosures by radio-telemetry for nine months. There was a continuous decline in nighttime breathing and heart rate, at constant Tb, throughout the late summer and fall suggestive of an active metabolic suppression that developed progressively at night preceding the entrance into dormancy. During the day, however, the tegus still emerged to bask. In May, when the tegus made a behavioural commitment to dormancy, Tb (day and night) fell to match burrow temperature, accompanied by a further reduction in fH and fR. Tegus, under the conditions of this study, did arouse periodically during dormancy. There was a complex interplay between changes in fH and Tb associated with the direct effects of temperature and the indirect effects of thermoregulation, activity, and changes in metabolism. This interplay gave rise to a daily hysteresis in the fH/Tb relationship reflective of the physiological changes associated with warming and cooling as preferred Tb alternated between daytime and nighttime levels. The shape of the hysteresis curve varied with season along with changes in metabolic state and daytime and nighttime body temperature preferences. PMID- 26266402 TI - Absorption-Enhancing Effects of Bile Salts. AB - Bile salts are ionic amphiphilic compounds with a steroid skeleton. Among the most important physiological properties of bile salts are lipid transport by solubilization and transport of some drugs through hydrophobic barriers. Bile salts have been extensively studied to enhance transepithelial permeability for different marker molecules and drugs. They readily agglomerate at concentrations above their critical micelle concentration (CMC). The mechanism of absorption enhancement by bile salts appears to be complex. The aim of the present article was to review bile salt structure and their application as absorption enhancers and the probable mechanism for increasing permeation based on previous studies. PMID- 26266403 TI - Anti-Inflammatory Activity of Heterocarpin from the Salt Marsh Plant Corydalis heterocarpa in LPS-Induced RAW 264.7 Macrophage Cells. AB - The inhibitory effect of three chromones 1-3 and two coumarins 4-5 on the production of nitric oxide (NO) was evaluated in LPS-induced RAW 264.7 macrophage cells. Among the compounds tested heterocarpin (1), a furochromone, significantly inhibited its production in a dose-dependent manner. In addition, heterocarpin suppressed prostaglandin E2 (PGE2) production and expression of cytokines such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6). PMID- 26266404 TI - Wnt3a Promotes the Vasculogenic Mimicry Formation of Colon Cancer via Wnt/beta Catenin Signaling. AB - Our previous study provided evidence that non-canonical Wnt signaling is involved in regulating vasculogenic mimicry (VM) formation. However, the functions of canonical Wnt signaling in VM formation have not yet been explored. In this study, we found the presence of VM was related to colon cancer histological differentiation (p < 0.001), the clinical stage (p < 0.001), and presence of metastasis and recurrence (p < 0.001). VM-positive colon cancer samples showed increased Wnt3a expression (p < 0.001) and beta-catenin nuclear expression (p < 0.001) compared with the VM-negative samples. In vitro, over-regulated Wnt3a expression in HT29 colon cancer cells promoted the capacity to form tube-like structures in the three-dimensional (3-D) culture together with increased expression of endothelial phenotype-associated proteins such as VEGFR2 and VE cadherin. The mouse xenograft model showed that Wnt3a-overexpressing cells grew into larger tumor masses and formed more VM than the control cells. In addition, the Wnt/beta-catenin signaling antagonist Dickkopf-1(Dkk1) can reverse the capacity to form tube-like structures and can decrease the expressions of VEGFR2 and VE-cadherin in Wnt3a-overexpressing cells. Taken together, our results suggest that Wnt/beta-catenin signaling is involved in VM formation in colon cancer and might contribute to the development of more accurate treatment modalities aimed at VM. PMID- 26266405 TI - Evaluation and Management of Neurogenic Bladder: What Is New in China? AB - Neurogenic bladder (NB) or neurogenic lower urinary tract dysfunction (NLUTD), a dysfunction of the urinary bladder and urethra due to disease of the central nervous system or peripheral nerves, is a major global medical and social problem. Numerous nervous system abnormalities, such as: stroke, Alzheimer's and Parkinson's diseases, traumatic spinal cord injury, spinal cord tumors, congenital spina bifida, and diabetes, can cause NB/NLUTD. There are two major types of bladder control problems associated with NB/NLUTD: the bladder becomes either overactive or underactive depending on the nature, level, and extent of nerve damage. This review specifically focuses on the diagnosis and management of NB/NLUTD in China as well as on recent efforts to treat this disease. PMID- 26266406 TI - Role of Pharmacogenetics in Hematopoietic Stem Cell Transplantation Outcome in Children. AB - Hematopoietic stem cell transplantation (HSCT) is an established therapeutic procedure for several congenital and acquired disorders, both malignant and nonmalignant. Despite the great improvements in HSCT clinical practices over the last few decades, complications, such as graft vs. host disease (GVHD) and sinusoidal obstructive syndrome (SOS), are still largely unpredictable and remain the major causes of morbidity and mortality. Both donor and patient genetic background might influence the success of bone marrow transplantation and could at least partially explain the inter-individual variability in HSCT outcome. This review summarizes some of the recent studies on candidate gene polymorphisms in HSCT, with particular reference to pediatric cohorts. The interest is especially focused on pharmacogenetic variants affecting myeloablative and immunosuppressive drugs, although genetic traits involved in SOS susceptibility and transplant related mortality are also reviewed. PMID- 26266407 TI - ALS-Linked P56S-VAPB Mutation Impairs the Formation of Multinuclear Myotube in C2C12 Cells. AB - Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder that affects upper and lower motor neurons. Since motor neurons target skeletal muscles, the maintenance system of muscles is disturbed in ALS; however, the mechanism by which this occurs is unknown. In the present study, we investigated the effects of ALS-associated P56S-vesicle-associated membrane protein-associated protein B (VAPB) (P56S-VAPB) on the IRE1-XBP1 pathway, which is involved in the unfolded protein response (UPR) of the mouse myoblast cell line (C2C12 cells). Experiments with C2C12 cells transfected with wild-type wt VAPB and P56S-VAPB expression vectors showed reduced myotube formation and aberrant myonuclear position in cells expressing P56S-VAPB. Activity of the IRE1 XBP1 pathway in the cells visualized with the ERAI system revealed that the pathway was disrupted in cells expressing P56S-VAPB, whereas the IRE1-XBP1 pathway activity was enhanced in the differentiation process of normal C2C12 cells. These results suggest that disruption of the IRE1-XBP1 pathway is a cause for the reduced myotube formation in P56S-VAPB-expressing cells. The expression level of the VAPB protein has been reported to be reduced in the neurons of patients with ALS. Therefore, it is expected that the IRE1-XBP1 pathway is also impaired in muscle tissues of patients with ALS, which causes a disturbance in the muscle maintenance system. PMID- 26266408 TI - Bioactive Compounds of Blueberries: Post-Harvest Factors Influencing the Nutritional Value of Products. AB - Blueberries, besides having commonly-recognized taste properties, are also a valuable source of health-promoting bioactive compounds. For several decades, blueberries have gained in popularity all over the world, and recent years have seen not only an increase in fresh consumption, but also in the importance of blueberries for the processing industry. Blueberry processing mostly consists of freezing and juicing. Recently, more attention has been drawn to dewatering and drying, which are promising areas for developing novel blueberry products. Processing affects each biologically-active compound in a different way, and it is still unknown what changes those compounds undergo at the molecular level after the application of different processing technologies. This work presents the most recent state of knowledge about the pre-treatment and processing methods applied to blueberries and their influence on the content of biologically-active compounds. The presentation of methods is preceded by a brief overview of the characteristics of the blueberry species, a description of the chemical composition of the fruit and a short note about the main growing areas, production volumes and the management of fruit crops. PMID- 26266410 TI - Distributed Wireless Monitoring System for Ullage and Temperature in Wine Barrels. AB - This paper presents a multipurpose and low cost sensor for the simultaneous monitoring of temperature and ullage of wine in barrels in two of the most important stages of winemaking, that being fermentation and maturation. The distributed sensor subsystem is imbedded within the bung of the barrel and runs on battery for a period of at least 12 months and costs around $27 AUD for all parts. In addition, software was designed which allows for the remote transmission and easy visual interpretation of the data for the winemaker. Early warning signals can be sent when the temperature or ullage deviates from a winemakers expectations so remedial action can be taken, such as when topping is required or the movement of the barrels to a cooler cellar location. Such knowledge of a wine's properties or storage conditions allows for a more precise control of the final wine quality. PMID- 26266409 TI - Changes of the Cytoplasmic Proteome in Response to Alcoholic Hepatotoxicity in Rats. AB - Proteomic analyses have already been used in a number of hepatological studies and provide important information. However, few reports have focused on changes in the cytoplasmic proteome. The present study therefore aimed to evaluate changes in cytoplasmic proteome of rats in response to alcoholic hepatotoxicity. Rats were fed a Liber-DeCarli liquid diet containing ethanol for four weeks. Cytoplasmic proteins except mitochondrial proteins from the livers of these animals were investigated using two-dimensional gel electrophoresis and mass spectrometry. Alcohol induced a decrease in body weight gain and an increase in alanine transaminase (ALT), cholesterol, and phospholipid levels. Histopathological observations revealed hepatic damage characterized by necrosis and fatty change in alcohol-treated group at week 2, which continues until week 4. Our proteomic analysis revealed that 25 proteins were differentially expressed in the ethanol-fed group. Of these, 12 cytoplasmic proteins are being reported for the first time. Taken together, our results provide further insights into the disease mechanism and therapeutic information of alcoholic liver disease. PMID- 26266411 TI - A Scalable Context-Aware Objective Function (SCAOF) of Routing Protocol for Agricultural Low-Power and Lossy Networks (RPAL). AB - In recent years, IoT (Internet of Things) technologies have seen great advances, particularly, the IPv6 Routing Protocol for Low-power and Lossy Networks (RPL), which provides a powerful and flexible routing framework that can be applied in a variety of application scenarios. In this context, as an important role of IoT, Wireless Sensor Networks (WSNs) can utilize RPL to design efficient routing protocols for a specific application to increase the ubiquity of networks with resource-constrained WSN nodes that are low-cost and easy to deploy. In this article, our work starts with the description of Agricultural Low-power and Lossy Networks (A-LLNs) complying with the LLN framework, and to clarify the requirements of this application-oriented routing solution. After a brief review of existing optimization techniques for RPL, our contribution is dedicated to a Scalable Context-Aware Objective Function (SCAOF) that can adapt RPL to the environmental monitoring of A-LLNs, through combining energy-aware, reliability aware, robustness-aware and resource-aware contexts according to the composite routing metrics approach. The correct behavior of this enhanced RPL version (RPAL) was verified by performance evaluations on both simulation and field tests. The obtained experimental results confirm that SCAOF can deliver the desired advantages on network lifetime extension, and high reliability and efficiency in different simulation scenarios and hardware testbeds. PMID- 26266412 TI - The Balanced Cross-Layer Design Routing Algorithm in Wireless Sensor Networks Using Fuzzy Logic. AB - Recently, the cross-layer design for the wireless sensor network communication protocol has become more and more important and popular. Considering the disadvantages of the traditional cross-layer routing algorithms, in this paper we propose a new fuzzy logic-based routing algorithm, named the Balanced Cross-layer Fuzzy Logic (BCFL) routing algorithm. In BCFL, we use the cross-layer parameters' dispersion as the fuzzy logic inference system inputs. Moreover, we give each cross-layer parameter a dynamic weight according the value of the dispersion. For getting a balanced solution, the parameter whose dispersion is large will have small weight, and vice versa. In order to compare it with the traditional cross layer routing algorithms, BCFL is evaluated through extensive simulations. The simulation results show that the new routing algorithm can handle the multiple constraints without increasing the complexity of the algorithm and can achieve the most balanced performance on selecting the next hop relay node. Moreover, the Balanced Cross-layer Fuzzy Logic routing algorithm can adapt to the dynamic changing of the network conditions and topology effectively. PMID- 26266413 TI - Secure and Authenticated Data Communication in Wireless Sensor Networks. AB - Securing communications in wireless sensor networks is increasingly important as the diversity of applications increases. However, even today, it is equally important for the measures employed to be energy efficient. For this reason, this publication analyzes the suitability of various cryptographic primitives for use in WSNs according to various criteria and, finally, describes a modular, PKI based framework for confidential, authenticated, secure communications in which most suitable primitives can be employed. Due to the limited capabilities of common WSN motes, criteria for the selection of primitives are security, power efficiency and memory requirements. The implementation of the framework and the singular components have been tested and benchmarked in our testbed of IRISmotes. PMID- 26266414 TI - Multi-Sensor Approach for the Monitoring of Halitosis Treatment via Lactobacillus brevis (CD2)-Containing Lozenges--A Randomized, Double-Blind Placebo-Controlled Clinical Trial. AB - The aim of this randomized clinical trial was to evaluate whether a recently described multi-sensor approach called BIONOTE((r)) is accurate enough to verify the efficacy of treatment of patients with halitosis. A treatment with Lactobacillus brevis (CD2)-containing lozenges, compared with placebo was tested. The BIONOTE((r)) was compared with traditional techniques used to detect halitosis: OralChromaTM and two calibrated odor judges enrolled for the organoleptic assessments. Twenty patients (10 treated and 10 placebo), suffering from active phase halitosis were included in the study. Treatment consisted of Lactobacillus brevis (CD2)-containing lozenges or placebo, 4 tablets/day for 14 days. t0 was before the beginning of the study; t1 was day 7 and t2 was day 14. The effectiveness of treatment was assessed through: (1) Rosenberg score; (2) Winkel tongue coating index (WTCI) anterior and posterior; (2) OralChromaTM; (3) the new developed multi-sensor approach, called BIONOTE((r)) (test technique). Only the WTCI anterior revealed statistically significant changes between t0 and t2 data (p = 0.014) in the treated group. Except for the WTCI anterior, all diagnostic methods revealed the lack of effectiveness for halitosis of a 14-days treatment with Lactobacillus brevis (CD2)-containing lozenges. The BIONOTE((r)) multisensor system seems accurate in addition to OralChromaTM to assess the initial condition of halitosis and its mitigation during treatment. PMID- 26266415 TI - Structure-Activity Relationships of the Bioactive Thiazinoquinone Marine Natural Products Thiaplidiaquinones A and B. AB - In an effort to more accurately define the mechanism of cell death and to establish structure-activity relationship requirements for the marine meroterpenoid alkaloids thiaplidiaquinones A and B, we have evaluated not only the natural products but also dioxothiazine regioisomers and two precursor quinones in a range of bioassays. While the natural products were found to be weak inducers of ROS in Jurkat cells, the dioxothiazine regioisomer of thiaplidiaquinone A and a synthetic precursor to thiaplidiaquinone B were found to be moderately potent inducers. Intriguingly, and in contrast to previous reports, the mechanism of Jurkat cell death (necrosis vs. apoptosis) was found to be dependent upon the positioning of one of the geranyl sidechains in the compounds with thiaplidiaquinone A and its dioxothiazine regioisomer causing death dominantly by necrosis, while thiaplidiaquinone B and its dioxothiazine isomer caused cell death via apoptosis. The dioxothiazine regioisomer of thiaplidiaquinone A exhibited more potent in vitro antiproliferative activity against human tumor cells, with NCI sub-panel selectivity towards melanoma cell lines. The non-natural dioxothiazine regioisomers were also more active in antiplasmodial and anti-farnesyltransferase assays than their natural product counterparts. The results highlight the important role that natural product total synthesis can play in not only helping understand the structural basis of biological activity of natural products, but also the discovery of new bioactive scaffolds. PMID- 26266416 TI - The Willingness-to-Pay for General Practitioners in Contractual Service and Influencing Factors among Empty Nesters in Chongqing, China. AB - BACKGROUND: In 2012, a pilot health policy of contractual service relations between general practitioners and patients was implemented in China. Due to the decline in body and cognitive function, as well as the lack of family care and narrow social support networks, the demand of health services among the elderly is much higher than that among the general population. This study aims to probe into the empty nesters' willingness-to-pay for general practitioners using a contractual service policy, investigating empty nesters' payment levels for the service, and analyze the main factors affecting the willingness of empty-nesters' general practitioners using contractual service supply cost. METHODS: This cross sectional study adopted a multistage stratified sampling method to survey 865, city empty nesters (six communities in three districts of one city) aged 60-85 years. A condition value method was used to infer the distribution of the willingness-to-pay; Cox's proportional hazards regression model was used to analyze the influencing factors of willingness-to-pay. RESULTS: More than seventy percent (76.6%) of the empty nesters in this city were willing to pay general practitioners using contract service in Chongqing. The level of willingness-to pay for the surveyed empty nesters was 34.1 yuan per year. The median value was 22.1 yuan per year, which was below the Chongqing urban and rural cooperative medical insurance individual funding level (60 yuan per year) in 2013. Cox's proportional hazards regression model analysis showed that the higher the education level was, the worse the self-reported health status would be, accompanied by higher family per capita income, higher satisfaction of community health service, and higher willingness-to-pay empty nesters using a contract service. Women had a higher willingness-to-pay than men. CONCLUSIONS: The willingness-to-pay for general practitioners by contractual service is high among city empty nesters in Chongqing, thus, individual financing is feasible. However, people are willing to pay less than half of the current personal financing of cooperative medical insurance of urban and rural residents. Education level, family per capita income, and self-reported health status are the main factors affecting the cost sharing intention for general practitioners using contract service supply. According to the existing situation of different empty nesters, it is important to perfect the design of general practitioners using a contractual service policy system, according to differentiated personal financing levels. PMID- 26266418 TI - eEF1A Interacts with the NS5A Protein and Inhibits the Growth of Classical Swine Fever Virus. AB - The NS5A protein of classical swine fever virus (CSFV) is involved in the RNA synthesis and viral replication. However, the NS5A-interacting cellular proteins engaged in the CSFV replication are poorly defined. Using yeast two-hybrid screen, the eukaryotic elongation factor 1A (eEF1A) was identified to be an NS5A binding partner. The NS5A-eEF1A interaction was confirmed by coimmunoprecipitation, glutathione S-transferase (GST) pulldown and laser confocal microscopy assays. The domain I of eEF1A was shown to be critical for the NS5A-eEF1A interaction. Overexpression of eEF1A suppressed the CSFV growth markedly, and conversely, knockdown of eEF1A enhanced the CSFV replication significantly. Furthermore, eEF1A, as well as NS5A, was found to reduce the translation efficiency of the internal ribosome entry site (IRES) of CSFV in a dose-dependent manner, as demonstrated by luciferase reporter assay. Streptavidin pulldown assay revealed that eEF1A could bind to the CSFV IRES. Collectively, our results suggest that eEF1A interacts with NS5A and negatively regulates the growth of CSFV. PMID- 26266417 TI - Replication and Inhibitors of Enteroviruses and Parechoviruses. AB - The Enterovirus (EV) and Parechovirus genera of the picornavirus family include many important human pathogens, including poliovirus, rhinovirus, EV-A71, EV-D68, and human parechoviruses (HPeV). They cause a wide variety of diseases, ranging from a simple common cold to life-threatening diseases such as encephalitis and myocarditis. At the moment, no antiviral therapy is available against these viruses and it is not feasible to develop vaccines against all EVs and HPeVs due to the great number of serotypes. Therefore, a lot of effort is being invested in the development of antiviral drugs. Both viral proteins and host proteins essential for virus replication can be used as targets for virus inhibitors. As such, a good understanding of the complex process of virus replication is pivotal in the design of antiviral strategies goes hand in hand with a good understanding of the complex process of virus replication. In this review, we will give an overview of the current state of knowledge of EV and HPeV replication and how this can be inhibited by small-molecule inhibitors. PMID- 26266421 TI - Ultrasound-Guided Injection of Botulinum Toxin Type A for Piriformis Muscle Syndrome: A Case Report and Review of the Literature. AB - Piriformis muscle syndrome (PMS) is caused by prolonged or excessive contraction of the piriformis muscle associated with pain in the buttocks, hips, and lower limbs because of the close proximity to the sciatic nerve. Botulinum toxin type A (BoNT-A) reduces muscle hypertonia as well as muscle contracture and pain inhibiting substance P release and other inflammatory factors. BoNT-A injection technique is important considering the difficult access of the needle for deep location, the small size of the muscle, and the proximity to neurovascular structures. Ultrasound guidance is easy to use and painless and several studies describe its use during BoNT-A administration in PMS. In the present review article, we briefly updated current knowledge regarding the BoNT therapy of PMS, describing also a case report in which this syndrome was treated with an ultrasound-guided injection of incobotulinumtoxin A. Pain reduction with an increase of hip articular range of motion in this patient with PMS confirmed the effectiveness of BoNT-A injection for the management of this syndrome. PMID- 26266420 TI - Homocysteine Metabolism Gene Polymorphisms (MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) Jointly Elevate the Risk of Folate Deficiency. AB - Folate deficiency is strongly associated with cardiovascular disease. We aimed to explore the joint effect of the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MTR) A2756G, and methionine synthase reductase (MTRR) A66G polymorphisms on folate deficiency in a Chinese hypertensive population. A total of 480 subjects aged 28-75 were enrolled in this study from September 2005-December 2005 from six hospitals in different Chinese regions. Known genotypes were detected by PCR-RFLP methods and serum folate was measured by chemiluminescence immunoassay. Our results showed that MTHFR 677TT and MTR 2756AG + GG were independently associated with a higher risk of folate deficiency (TT vs. CC + CT, p < 0.001 and AG + GG vs. AA p = 0.030, respectively). However, the MTHFR A1298C mutation may confer protection by elevating the serum folate level (p = 0.025). Furthermore, patients carrying two or more risk genotypes showed higher odds of folate deficiency than null risk genotype carriers, especially those carrying four risk genotypes. These findings were verified by generalized multifactor dimensionality reduction (p = 0.0107) and a cumulative effects model (p = 0.001). The results of this study have shown that interactions among homocysteine metabolism gene polymorphisms lead to dramatic elevations in the folate deficiency risk. PMID- 26266419 TI - Development of the Intervention Materials for the HomeStyles Obesity Prevention Program for Parents of Preschoolers. AB - Home environment is key to the development of obesity-preventing behaviors during childhood, yet few resources help preschool parents address factors at home associated with obesity risk. This paper describes creation of materials for an in-home intervention (HomeStyles) with this population. An advisory group of stakeholders and target audience members determined salient factors affecting childhood obesity to address in-home and developed program materials. The Social Cognitive Theory, Faith's Core Behavior Change Strategies to Treat Childhood Obesity, Adult Learning Theory and motivational interviewing techniques guided development of 12 guides targeting strategies parents can use to shape the home environment. Interviews were conducted to determine effectiveness of the guides. Cognitive testing of guide design (n = 251) and content (n = 261) occurred in English and Spanish in New Jersey and Arizona with parents and home visitation staff who would present the guides. Interviews investigated perceptions of content usefulness and parent comprehension. Findings were also examined in light of theoretical underpinnings. Both home visitation staff and parents felt the guides were very readable and useful. Parents appreciated use of motivational interviewing techniques and Adult Learning Theory. Current research is testing these guides through an in-home, randomized control trial. PMID- 26266423 TI - Treatment of Regional Metastatic Melanoma of Unknown Primary Origin. AB - (1) BACKGROUND: The purpose of this retrospective study was to evaluate the recurrence and survival rates of metastatic melanoma of unknown primary origin (MUP), in order to further refine current recommendations for the surgical treatment; (2) METHODS: Medical data of all MUP patients registered between 2000 and 2011, were analyzed. Seventy-eight patients were categorized in either lymph node (axilla, groin, head-and neck) or subcutaneous MUP. Axillary node MUPs were generally treated with dissections of levels I-III, inguinal node MUPs with combined superficial and deep groin dissections, and head-and-neck node MUPs with neck dissections to various extents, based on lymph drainage patterns. Subcutaneous lesions were excised with 1-2 cm margins. The primary outcome was treatment outcomes in terms of (loco)regional recurrence and survival rates; (3) RESULTS: Lymph node MUP recurred regionally in 11% of patients, with an overall recurrence rate of 45%. In contrast, subcutaneous MUP recurred locally in 65% of patients with an overall recurrence rate of 78%. This latter group had a significantly shorter disease-free interval than patients with lymph node MUP (p = 0.000). In the entire study population, 5-year and 10-year overall survival rates were 56% and 47% respectively, with no differences observed between the various subgroups; (4) CONCLUSION: The relatively low regional recurrence rate after regional lymph node dissection (11%) supports its current status as standard surgical treatment for lymph node MUP. Subcutaneous MUP, on the contrary, appears to recur both locally (65%) and overall (78%) at a significantly higher rate, suggesting a different biological behavior. However, wide local excision remains the best available option for this specific group. PMID- 26266422 TI - Molecular Targeted Intervention for Pancreatic Cancer. AB - Pancreatic cancer (PC) remains one of the worst cancers, with almost uniform lethality. PC risk is associated with westernized diet, tobacco, alcohol, obesity, chronic pancreatitis, and family history of pancreatic cancer. New targeted agents and the use of various therapeutic combinations have yet to provide adequate treatments for patients with advanced cancer. To design better preventive and/or treatment strategies against PC, knowledge of PC pathogenesis at the molecular level is vital. With the advent of genetically modified animals, significant advances have been made in understanding the molecular biology and pathogenesis of PC. Currently, several clinical trials and preclinical evaluations are underway to investigate novel agents that target signaling defects in PC. An important consideration in evaluating novel drugs is determining whether an agent can reach the target in concentrations effective to treat the disease. Recently, we have reported evidence for chemoprevention of PC. Here, we provide a comprehensive review of current updates on molecularly targeted interventions, as well as dietary, phytochemical, immunoregulatory, and microenvironment-based approaches for the development of novel therapeutic and preventive regimens. Special attention is given to prevention and treatment in preclinical genetically engineered mouse studies and human clinical studies. PMID- 26266424 TI - The Human Factors and Ergonomics of P300-Based Brain-Computer Interfaces. AB - Individuals with severe neuromuscular impairments face many challenges in communication and manipulation of the environment. Brain-computer interfaces (BCIs) show promise in presenting real-world applications that can provide such individuals with the means to interact with the world using only brain waves. Although there has been a growing body of research in recent years, much relates only to technology, and not to technology in use-i.e., real-world assistive technology employed by users. This review examined the literature to highlight studies that implicate the human factors and ergonomics (HFE) of P300-based BCIs. We assessed 21 studies on three topics to speak directly to improving the HFE of these systems: (1) alternative signal evocation methods within the oddball paradigm; (2) environmental interventions to improve user performance and satisfaction within the constraints of current BCI systems; and (3) measures and methods of measuring user acceptance. We found that HFE is central to the performance of P300-based BCI systems, although researchers do not often make explicit this connection. Incorporation of measures of user acceptance and rigorous usability evaluations, increased engagement of disabled users as test participants, and greater realism in testing will help progress the advancement of P300-based BCI systems in assistive applications. PMID- 26266426 TI - Bio-Inspired Aquaporinz Containing Double-Skinned Forward Osmosis Membrane Synthesized through Layer-by-Layer Assembly. AB - We demonstrated a novel AquaporinZ (AqpZ)-incorporated double-skinned forward osmosis (FO) membrane by layer-by-layer (LbL) assembly strategy. Positively charged poly(ethyleneimine) (PEI) and negatively charged poly(sodium 4 styrenesulfonate) (PSS) were alternately deposited on both the top and bottom surfaces of a hydrolyzed polyacrylonitrile (H-PAN) substrate. Subsequently, an AqpZ-embedded 1,2-dioleloyl-sn-glycero-3-phosphocholine (DOPC)/1,2-dioleoyl-3 trimethylammonium- propane (chloride salt) (DOTAP) supported lipid bilayer (SLB) was formed on PSS-terminated (T-PSS) membrane via vesicle rupture method. The morphology and structure of the biomimetic membranes were characterized by in situ atomic force microscopy (AFM), scanning electron microscope (SEM), Fourier transform infrared spectrometer using the attenuated total reflection technique (ATR-FTIR), and contact angle. Moreover, the FO performance of the resultant membrane was measured by using 2 M MgCl2 solution as draw solution and deionized (DI) water as feed solution, respectively. The membrane with a protein-to-lipid weight ratio (P/L) of 1/50 exhibits 13.2 L/m(2)h water flux and 3.2 g/m(2)h reversed flux by using FO mode, as well as 15.6 L/m(2)h water flux and 3.4 L/m(2)h reversed flux for PRO mode (the draw solution is placed against the active layer). It was also shown that the SLB layer of the double-skinned FO membrane can increase the surface hydrophilicity and reduce the surface roughness, which leads to an improved anti-fouling performance against humic acid foulant. The current work introduced a new method of fabricating high performance biomimetic FO membrane by combining AqpZ and a double-skinned structure based on LbL assembly. PMID- 26266425 TI - Can Stabilization and Inhibition of Aquaporins Contribute to Future Development of Biomimetic Membranes? AB - In recent years, the use of biomimetic membranes that incorporate membrane proteins, i.e., biomimetic-hybrid membranes, has increased almost exponentially. Key membrane proteins in these systems have been aquaporins, which selectively permeabilize cellular membranes to water. Aquaporins may be incorporated into synthetic lipid bilayers or to more stable structures made of block copolymers or solid-state nanopores. However, translocation of aquaporins to these alien environments has adverse consequences in terms of performance and stability. Aquaporins incorporated in biomimetic membranes for use in water purification and desalination should also withstand the harsh environment that may prevail in these conditions, such as high pressure, and presence of salt or other chemicals. In this respect, modified aquaporins that can be adapted to these new environments should be developed. Another challenge is that biomimetic membranes that incorporate high densities of aquaporin should be defect-free, and this can only be efficiently ascertained with the availability of completely inactive mutants that behave otherwise like the wild type aquaporin, or with effective non toxic water channel inhibitors that are so far inexistent. In this review, we describe approaches that can potentially be used to overcome these challenges. PMID- 26266427 TI - Phase 3 Randomized Double-Masked Study of Efficacy and Safety of Once-Daily 0.77% Olopatadine Hydrochloride Ophthalmic Solution in Subjects With Allergic Conjunctivitis Using the Conjunctival Allergen Challenge Model. AB - PURPOSE: To assess the efficacy and safety of a novel once-daily 0.77% olopatadine hydrochloride ophthalmic solution in subjects with allergic conjunctivitis (AC) using the conjunctival allergen challenge (CAC) model. METHODS: In this 5-week, multicenter, double-masked, phase 3, randomized trial, subjects aged >=18 years with a history of AC and a confirmed positive bilateral CAC response were randomized 2:2:2:1 to receive olopatadine 0.77%, olopatadine 0.2%, olopatadine 0.1%, or vehicle, respectively, following a single topical dose in each eye. The primary objective was superiority of olopatadine 0.77% over all comparators on ocular itching according to a 0 to 4 scale (0 = none and 4 = incapacitating itch) at 24-hour duration of action and over vehicle only at the onset of action (3, 5, and 7 minutes after CAC for both). RESULTS: In total, 345 subjects were randomized. Olopatadine 0.77% was superior to the vehicle at alleviating ocular itching at all post-CAC time points at the onset of action and at 24 hours (difference in means: -0.9 to -1.5; P < 0.0001). Superiority in relieving ocular itching was also demonstrated for olopatadine 0.77% versus olopatadine 0.2% and 0.1% at 24 hours (difference in means: -0.3 to -0.5; P < 0.05). Additionally, olopatadine 0.77% significantly improved conjunctival redness and total redness compared with all comparators at the onset of action (differences in means: -0.3 to -0.6 and -0.8 to -2.0, respectively; both P < 0.05). No safety concerns for olopatadine 0.77% were identified. CONCLUSIONS: Olopatadine 0.77% demonstrated a rapid onset and prolonged duration of action. It was superior to all comparators in alleviating AC-associated ocular itching with a favorable safety profile.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01743027. PMID- 26266428 TI - Inhibition of Pathologic Corneal Neovascularization by Topical Application of a Novel Peptide In Vivo. AB - PURPOSE: To investigate the antiangiogenic effect of topical application of H KI20, a novel 20-amino acid peptide from the hepatocyte growth factor, on 2 animal models of corneal neovascularization (NV), and its possible toxic effects on the cornea and conjunctiva. METHODS: The antiangiogenic effect of topical H KI20 in vivo was studied on corneal NV induced by a mouse corneal micropocket assay and rat intrastromal suture model. In each model, H-KI20, scrambled control peptide H-KI20S, bevacizumab, and phosphate buffer solution (PBS) were applied topically 4 times a day. Corneal NV was examined, photographed, and analyzed. Histological analysis of the corneas was performed. Tear film breakup time and gross and histological examinations were used to study the possible toxicity of topical H-KI20. RESULTS: Topical application of H-KI20 significantly inhibited corneal NV induced by vascular endothelial growth factor (VEGF), and intrastromal suture (P < 0.01 vs. the PBS group), and the area of corneal NV was suppressed by 80.3% and 83.6%, respectively (PBS group as 100%). No significant difference was found between 1.0 mg/mL H-KI20 and 10 mg/mL bevacizumab (P > 0.05). Both hematoxylin and eosin and CD34 staining revealed fewer new blood vessels in the H KI20 and bevacizumab groups. Tear film breakup time and histological examinations showed that H-KI20 had no obvious toxic effects on the cornea and conjunctiva in vivo. CONCLUSIONS: The novel peptide H-KI20 is an effective and safe inhibitor of corneal NV. It may provide a promising alternative for ocular topical antiangiogenic therapy. PMID- 26266429 TI - Comparison of Tear Meniscus Height Measurements Obtained With the Keratograph and Fourier Domain Optical Coherence Tomography in Dry Eye. AB - PURPOSE: To study the repeatability and reproducibility of tear meniscus height (TMH) measurements obtained with a keratograph and Fourier domain optical coherence tomography (FD-OCT) and to assess their agreement in patients with dry eye. METHODS: Sixty-four eyes with dry eye were analyzed by the Schirmer test, tear breakup time test, and fluorescein corneal staining. The TMH was measured 3 times using both devices by 2 different examiners. The repeatability and reproducibility of measurements were assessed by within-subject standard deviation (Sw), repeatability (2.77 Sw), coefficient of variation (CoV), and intraclass correlation coefficient. RESULTS: The TMH measured with the keratograph and FD-OCT was 0.232 +/- 0.074 mm and 0.308 +/- 0.129 mm, respectively (P < 0.01). A close correlation was found between the TMH measured with the keratograph and FD-OCT (r = 0.343). There was a negative correlation between the mean TMH and differences in the TMH measured with the keratograph and FD-OCT (r = 0.359). Both measurements correlated with the Schirmer test score, tear breakup time, and corneal staining score with P < 0.01. Intraexaminer CoV, 2.77 Sw, and intraclass correlation coefficient of the TMH were <6.5%, <0.059 mm, and >0.986, respectively, and interexaminer CoV and 2.77 Sw were 5.58% and 0.039 mm, respectively. CONCLUSIONS: Although the TMH measured with the keratograph tended to be lower than that measured with FD-OCT, the TMH measured with the keratograph closely correlated with the TMH measured with FD-OCT and conventional tests and had good repeatability and reliability. PMID- 26266430 TI - Contralateral Eye Comparison Between Femtosecond Small Incision Intrastromal Lenticule Extraction at Depths of 100 and 160 MUm. AB - PURPOSE: To compare the visual results, higher-order aberrations, and corneal biomechanical properties of femtosecond small incision lenticule extraction (SMILE) at depths of 100 and 160 MUm. METHODS: A prospective comparative interventional clinical trial of a series of patients who underwent SMILE. In the right eye, a refractive lenticule was created at a depth of 100 MUm, and in the left eye, a depth of 160 MUm was used. Manifest refraction, uncorrected visual acuity, total high-order aberrations (THOA), and corneal biomechanical properties of both eyes were evaluated 1 month postoperatively. RESULTS: Thirty patients with bilaterally stable refractive errors were included in this study. One month postoperatively, mean corneal hysteresis was 9.71 +/- 0.68 in the right eyes and 9.97 +/- 0.77 in the left eyes, whereas the mean corneal resistant factor was 9.13 +/- 1.04 and 9.31 +/- 0.92 in the right and left eyes, respectively. Both corneal hysteresis and corneal resistant factor showed statistically significantly higher values in the left eyes (lenticule at a depth of 160 MUm). No statistically significant differences were found between the right and the left eyes regarding manifest refraction, uncorrected visual acuity, and THOA. CONCLUSIONS: Creating the refractive lenticule at a depth of 160 MUm in SMILE had less effect on the corneal biomechanics than did creating a lenticule at a depth of 100 MUm with no statistically significant differences in the refractive outcome and THOA between both groups. PMID- 26266431 TI - Management of Ocular Neuropathic Pain With Vitamin B12 Supplements: A Case Report. AB - PURPOSE: To report the case of a 28-year-old patient with persistent bilateral burning pain and foreign body sensation in both eyes for the past 1 year. The patient showed a poor response to 0.05% cyclosporine eye drops and frequent instillations of artificial tears. Ocular examination showed few superficial punctate epithelial defects, well-positioned laser in situ keratomileusis (performed 5 years ago with symptomless recovery) flaps, and clear interfaces bilaterally, with a tear film breakup time of 7 and 8 seconds in the right and left eyes, respectively. The results of Schirmer tests, confocal microscopy, corneal esthesiometry, and meibography were normal for both eyes. The patient was incidentally diagnosed with vitamin B12 deficiency, with a serum vitamin B12 value of 90 pg/mL (reference range, 236-911 pg/mL), during routine laboratory tests. In view of weak correlation between signs and symptoms, a putative diagnosis of ocular neuropathic pain secondary to vitamin B12 deficiency was made. METHODS: Case report. RESULTS: The patient was treated with parenteral vitamin B12, and topical therapy was continued without any changes. The patient experienced dramatic improvement with a decrease in symptoms within 3 weeks of administering vitamin B12 supplements and was symptom-free in the absence of any topical medication 6 months after treatment. CONCLUSIONS: Vitamin B12 deficiency, although common in India, has not been reported to be associated with ocular symptoms, including pain and mimicking those seen in severe dry eye. Vitamin B12 deficiency should be considered in the differential diagnosis of ocular neuropathic pain and dry eye in patients presenting with recalcitrant ocular neuropathic pain. PMID- 26266432 TI - Fluctuations of Corneal Sensitivity in Dry Eye Syndromes--A Longitudinal Pilot Study. AB - PURPOSE: The aim of this study was to observe corneal sensitivity (CoS) longitudinally in patients with dry eye and to evaluate the correlation between CoS, severity, and the etiology of dry eye syndrome (DES). METHODS: In this prospective study, 46 patients with DES were examined on 4 occasions within 3 months. CoS was measured by the Cochet-Bonnet esthesiometer. Tear films were evaluated for lipid layer thickness, breakup time, fluorescein and lissamine green staining, and Schirmer test. Patients were classified into etiologic subgroups: hormonal, immunologic, toxic, neural, and environmental. For statistical statistics, Mann-Whitney and Kruskal-Wallis tests were used. RESULTS: Serial data curves of CoS demonstrated pronounced variability of values. CoS and SICCA scores were negatively correlated (r = -0.454, P = 0.007). The Schirmer test and CoS were positively correlated (r = 0.363, P = 0.013). The environmental group had the highest CoS values (5.5). There was no significant difference in CoS neither between nerve-induced and nonnerve-induced DES groups (P = 0.858) nor within the subgroups (P = 0.118). During 3 months, CoS increased in all patients (4.8-5.1). The DES severity was negatively correlated with CoS, indicating a reduction of neural function in severe DES. CONCLUSIONS: Our results showed diminished CoS in severe dry eye although there was a high variability of CoS. This supports the hypothesis of different states of compensation as the disease continues and an association of CoS with different causes of dry eye. However, no statistical differences were found between etiological subgroups. PMID- 26266433 TI - Tenonplasty Combined With Free Oral Buccal Mucosa Autografts for Repair of Sclerocorneal Melt Caused by Chemical Burns. AB - PURPOSE: To describe a surgical technique for repair of an intractable sclerocorneal melt caused by a serious chemical burn. METHODS: This study includes a technique description and review of 3 representative cases. RESULTS: The combination of tenonplasty with a free oral buccal mucosa autograft was used in 3 patients with sclerocorneal melts caused by chemical burns. Promising results were found in each of them. The area of the sclerocorneal melt healed successfully after surgery, and the integrities of the eyeballs were salvaged. CONCLUSIONS: This technique provides a new method for surgical repair of an intractable sclerocorneal melt caused by a chemical burn. PMID- 26266434 TI - Corneal Cross-Linking for Brittle Cornea Syndrome. AB - PURPOSE: To describe corneal cross-linking (CXL) as a treatment option for brittle cornea syndrome (BCS). METHODS: Case report. RESULTS: Ethical decision making enabled bilateral sequential transepithelial CXL in an 11-year-old girl with BCS. Postoperative courses were uneventful with a bilateral stromal demarcation line, unchanged corneal transparency, constant endothelial cell density, and stable topography 2 years after intervention. CONCLUSIONS: Modified CXL can safely be performed in patients with BCS. Ethical review may be helpful for interventions deviating from standard practice. PMID- 26266435 TI - Herpes Simplex Virus Disease of the Anterior Segment in Children. AB - PURPOSE: To analyze the clinical presentation, characteristics, treatment, recurrences, and final outcomes and complications of herpes simplex virus (HSV) disease of the anterior segment in patients aged 17 years or younger. METHODS: This is an observational and retrospective study with review of the medical records of all the children diagnosed with herpes simplex infection of the anterior segment at an ophthalmologic referral center, from 2002 to 2012. The diagnosis was made on the basis of the history and examination of patients and in specific cases by viral culture and the polymerase chain reaction. Main outcome measurements included final visual acuity, bilateral disease, and recurrence. Recurrent disease was analyzed with Kaplan-Meier curves. RESULTS: A total of 103 patients were included with a median age at presentation of 9 years. Of them, 6 had bilateral and simultaneous disease. The median follow-up time was 18 months (range, 18 days-12 years). The most common clinical manifestations were epithelial dendritic keratitis in 42 eyes (38.5%) and interstitial keratitis in 39 eyes (35.7%), with 15 patients presenting multiple forms of HSV disease. The median final visual acuity in the group of patients was 20/40. Recurrent disease was evident in 42 (38.5%) of the eyes, with a median recurrence time of 15 months (95% confidence interval, 8.1-26.2 months). CONCLUSIONS: In this study, epithelial dendritic and interstitial keratitis were the most frequent forms of disease in the pediatric population with HSV of the anterior segment. A high rate of recurrent disease was present. PMID- 26266436 TI - Transepithelial Versus Epithelium-Off Corneal Collagen Cross-Linking for Progressive Keratoconus: A Prospective Randomized Controlled Trial. AB - PURPOSE: To compare the safety and efficacy of transepithelial with epithelium off corneal cross-linking for progressive keratoconus. METHODS: In a prospective clinical trial, 70 patients with progressive keratoconus were randomized to undergo corneal cross-linking with intact epithelium (n = 34) or after deepithelialization (n = 36). The main outcome measure was a change in the maximum K reading (K(max)). RESULTS: With 3-year follow-up, K(max) decreased in the epithelium-off group with a mean of 2.4 D and no patient showed evidence of progression. In the transepithelial group, K(max) increased by a mean of 1.1 D, and 20 patients (55%) showed progression of keratoconus. CONCLUSIONS: In this study, epithelium-off was significantly more effective than transepithelial corneal cross-linking in halting the progression of keratoconus (P < 0.0001). PMID- 26266437 TI - Ocular Surface Epithelialization Pattern After Simple Limbal Epithelial Transplantation: An In Vivo Observational Study. AB - PURPOSE: To study the in vivo pattern of ocular surface epithelialization after simple limbal epithelial transplantation (SLET). METHODS: A retrospective interventional case series was performed at a cornea and anterior segment services of a referral tertiary care center between June 2012 and March 2015. Patients with unilateral limbal stem cell deficiency who underwent SLET and whose medical records had serial and detailed photographic documentation of ocular surface healing were reviewed. The outcome measures consisted of the pattern of ocular surface epithelialization, time taken for complete ocular surface epithelialization, and assessment of the possible variations in the explants' characteristics in vivo. RESULTS: Five patients fulfilled the inclusion criteria. Mean age was 30.8 years, the male:female ratio was 4:1. Mean follow-up after the SLET period was 10.8 months. A 2-line improvement in visual acuity was seen in 3 of 5 patients. The mean number of explants was 11.4 (range, 5-19). The first clinical evidence of proliferation of the corneal epithelium from the limbal explants was seen on the second day in all patients, and ocular surface epithelialization was complete in all cases within 14 days. The explants disappeared within 1 to 2 months in all but 1 case (24 weeks). Variations were seen in explant activity with the size and age of the explants. CONCLUSIONS: The in vivo pattern of ocular surface epithelialization after SLET appears to be similar to in vitro epithelialization observed after CLET. The observations in this study provide a lead for performing further laboratory and clinical research in SLET. PMID- 26266438 TI - Corneal Transplantation in the Developing World: Lessons Learned and Meeting the Challenge. AB - PURPOSE: To describe the current state of corneal blindness (CB) and corneal transplantation in the developing world. METHODS: Information on corneal transplantation was obtained from published articles, direct communication with corneal specialists in developing countries, data sourced from eye banks in the United States and abroad, and personal experience. RESULTS: CB is the fourth leading cause of global blindness. Most of those with CB live in India and Africa. Many developing countries lack sustainable eye banks, and there is a shortage of corneal transplant surgeons. India has started programs to address both these issues, whereas Africa seems the least prepared. Brazil and the Philippines have also made significant progress in eye banking. In addition, studies indicate a role for the use of a keratoprosthesis in select settings. Several international organizations and academic centers have targeted these system-wide deficiencies. CONCLUSIONS: There are an unacceptable number of people with cornea blindness in the developing world. Programs have been initiated to address eye bank sustainability and to increase surgeon capacity. However, much more work and effort will be needed to improve the current statistics. PMID- 26266439 TI - Response to "Pachymetry-Guided Intrastromal Air Injection ("Pachy-Bubble") for Deep Anterior Lamellar Keratoplasty: Results of the First 110 Cases". PMID- 26266440 TI - Acute toxicity of binary-metal mixtures of copper, zinc, and nickel to Pimephales promelas: Evidence of more-than-additive effect. AB - Metal mixture toxicity has been studied for decades. However, the results are not consistent, and thus ecological risk assessment and regulation of mixtures has been difficult. The objective of the present study was to use a systematic experimental design to characterize the toxicity of binary-metal mixture of Cu, Zn, and Ni to Pimephales promelas, typically to determine whether the effect of these binary-metal mixtures on P. promelas is more-than-additive. Standard 96-h toxicity tests were conducted with larval P. promelas based on US Environmental and Protection Agency methods to determine metal mixture effects. All experiments were conducted in synthetic moderately hard water with no addition of dissolved organic matter. Three different effect analysis approaches, the MixTox model, the Finney model, and the toxic unit method, were used for comparison. The results indicate that the toxicity of Cu+Zn, Cu+Ni, and Zn+Ni mixtures to P. promelas was more-than-additive. Among the 3 mixtures, the effect of the Cu+Ni mixture was the most profound. The results of the present study are useful for applications to models such as the metal mixture biotic ligand model. More research should be conducted to determine the mechanisms of acute and chronic toxicity of metal mixtures. PMID- 26266441 TI - The NMC may be doing better, but it's still failing. PMID- 26266442 TI - The BJN Award: recognising the role of unpaid nurses. PMID- 26266443 TI - Safeguarding the welfare of children: what is the nurse's role? AB - Everyone who works with children, including teachers, GPs, other medical professionals and the police, has a responsibility to keep children safe and protect them from harm. Simply put, safeguarding children is everyone's responsibility. Children should be protected from maltreatment and any impairment that may affect their health and development. In addition, we all have to ensure that children grow up with safe and effective care. At particular risk, and therefore in particular need of safeguarding, are children who are disabled; who have educational or other specific additional needs; and who bear signs of child abuse, substance abuse, or domestic violence. Under the Children Act 1989, local authorities are required to provide services for children in need for the purposes of safeguarding and promoting their welfare. Nurses are well-placed to identify children and young people who may be at risk, and to act to safeguard them. Nurses and other health professionals should be familiar with local referral arrangements, usually to children's social care. PMID- 26266444 TI - Impact of commissioning weight-loss surgery for bariatric patients. AB - Obesity is a major UK public health issue that is increasingly costly to an individual's personal health, the NHS and society. It requires an immediate intervention, as well as a long-term strategy to decrease the rising rates of obesity. NHS England (2013) has published a policy to commission bariatric surgery for carefully selected individuals according to National Institute for Health and Care Excellence (NICE) guidelines (NICE, 2006). This has been shown to be a clinically and cost effective weight-loss treatment option (Picot et al, 2009), but is invasive and expensive compared with non-surgical weight-loss programmes. In addition, there remains inequality in access to bariatric care services across England, thereby preventing potentially eligible patients from getting the treatment they need. Further clarity is required regarding the commissioning responsibilities across the four tiers of the obesity care services. This clarity would help to achieve a more 'joined-up' clinical pathway that is focused at a local level to improve access. However, there is criticism that too much funding is currently being invested in the provision of bariatric surgery when it could be better spent on national roll-out programmes for intensive lifestyle interventions that promote more sustainable weight loss across England. PMID- 26266445 TI - Learning to nurse: combining simulation with key theory. AB - Following a recent Nursing and Midwifery Council revalidation of a university undergraduate nursing programme, simulation skills sessions and anatomy and physiology theory were integrated into one unit (module). This was done in order to integrate the basis for patient assessment and care provision with the anatomical and physiological theory and thereby enhance student learning and nursing practice. Students evaluated the new unit well and valued the close link between theory and practice simulation. Improvements were seen in the simulation skills sessions as students were better able to apply their underlying theory to their actions. Learning was enhanced as both simulation and theory were seen as more meaningful to practice and patient care. PMID- 26266446 TI - Making a connection: the key to humanised care. PMID- 26266447 TI - Being equipped to care for patients at risk of self-harm and suicide. PMID- 26266448 TI - Valuing the workforce: staff wellbeing and patient care. PMID- 26266449 TI - Mental health care beyond prison. PMID- 26266450 TI - The Care Quality Commission hospital inspection process. PMID- 26266451 TI - Looking to other countries for lessons learned. PMID- 26266452 TI - Legal regulation of the management of waste. AB - Healthcare providers such as hospitals and clinics have a duty of care under the Environmental Protection Act 1990 and its regulations to ensure that the waste they produce does not cause pollution or present a hazard to health. Nurses are well placed to ensure that the trust they work for discharge that duty. In this article, Richard Griffith outlines the legislation regulating the safe management and disposal of waste and considers how the law applies to nurses. PMID- 26266453 TI - Relationships: from staff nurse to nurse consultant. Part 11: with yourself. PMID- 26266454 TI - Telling the truth--it's complicated. PMID- 26266455 TI - Single-molecule protein sequencing through fingerprinting: computational assessment. AB - Proteins are vital in all biological systems as they constitute the main structural and functional components of cells. Recent advances in mass spectrometry have brought the promise of complete proteomics by helping draft the human proteome. Yet, this commonly used protein sequencing technique has fundamental limitations in sensitivity. Here we propose a method for single molecule (SM) protein sequencing. A major challenge lies in the fact that proteins are composed of 20 different amino acids, which demands 20 molecular reporters. We computationally demonstrate that it suffices to measure only two types of amino acids to identify proteins and suggest an experimental scheme using SM fluorescence. When achieved, this highly sensitive approach will result in a paradigm shift in proteomics, with major impact in the biological and medical sciences. PMID- 26266456 TI - Molecular dynamics study of interfacial thermal transport between silicene and substrates. AB - In this work, the interfacial thermal transport across silicene and various substrates, i.e., crystalline silicon (c-Si), amorphous silicon (a-Si), crystalline silica (c-SiO2) and amorphous silica (a-SiO2) are explored by classical molecular dynamics (MD) simulations. A transient pulsed heating technique is applied in this work to characterize the interfacial thermal resistance in all hybrid systems. It is reported that the interfacial thermal resistances between silicene and all substrates decrease nearly 40% with temperature from 100 K to 400 K, which is due to the enhanced phonon couplings from the anharmonicity effect. Analysis of phonon power spectra of all systems is performed to interpret simulation results. Contradictory to the traditional thought that amorphous structures tend to have poor thermal transport capabilities due to the disordered atomic configurations, it is calculated that amorphous silicon and silica substrates facilitate the interfacial thermal transport compared with their crystalline structures. Besides, the coupling effect from substrates can improve the interface thermal transport up to 43.5% for coupling strengths chi from 1.0 to 2.0. Our results provide fundamental knowledge and rational guidelines for the design and development of the next generation silicene-based nanoelectronics and thermal interface materials. PMID- 26266457 TI - Oxidative stress, antioxidants and periodontal disease. PMID- 26266458 TI - Surfactants as Promising Media for the Preparation of Crystalline Inorganic Materials. AB - Given that surfactants can control the shape and size of micro-/nanoparticles, they should be able to direct the growth of bulk crystals. This Minireview summarizes recent developments in the application of surfactants for the preparation of new crystalline inorganic materials, including chalcogenides, metal-organic frameworks, and zeolite analogues. The roles of surfactants in different reaction systems are discussed. PMID- 26266459 TI - Treatment strategies for severe oligoasthenoteratozoospermia (OAT) (<0.1 million/mL) patients. AB - Intracytoplasmic sperm injection (ICSI) using spermatozoa from patients with severe oligoasthenoteratozoospermia is still a challenge. Although spermatozoa are available, lower fertilisation rates as well as compromised pregnancy rates are observed after ICSI. We aimed at identifying respective parameters in the pre values of ejaculate samples used for couple counselling. The clinical pre-values of 121 patients and their corresponding 228 ICSI cycles performed between 2002 and 2010 were retrospectively analysed. Patients were divided into three groups: (i) group 1 (G1, n = 51) where all patients showed at least once <0.1 million/mL and ICSI was performed using ejaculate alone; (ii) group 2 (G2, n = 14) patients had once <0.1 Mill/mL or azoospermia and a testicular biopsy before start of ICSI; (iii) group 3 (G3, n = 56) patients were azoospermic and directed immediately to testicular sperm extraction (TESE). The pre-values of G2 differed significantly from G1 in terms of volume and motility. Lutenizing hormone (LH) and follicle-stimulating hormone (FSH) values were equal in G1 and G2, but showed significant differences in comparison to G3. Testis volume was significantly higher in G3. In the corresponding ICSI cycles, the percentage of cancelled embryo transfers was highest in G3. We did not find any correlations of hormonal markers or sperm pre-values with the success rates of ICSI. In our patient cohort, spermatozoa retrieved either from ejaculate or testicular biopsies have nearly identical chances in achieving pregnancies. Patients in need of TESE before ICSI have significantly lower sperm counts. However, it is not possible to calculate threshold values as indicator for TESE. PMID- 26266460 TI - Good Neighbors: Shared Challenges and Solutions Toward Increasing Value at Academic Medical Centers and Universities. AB - Academic medical centers (AMCs) and universities are experiencing increasing pressure to enhance the value they offer at the same time that they are facing challenges related to outcomes, controlling costs, new competition, and government mandates. Yet, rarely do the leaders of these academic neighbors work cooperatively to enhance value. In this Perspective the author, a former university regional campus president with duties in an AMC as an academic physician, shares his insights into the shared challenges these academic neighbors face in improving the value of their services in complex environments. He describes the successes some AMCs have had in generating revenues from new clinical programs that reduce the overall cost of care for larger populations. He also describes how several universities have taken a comprehensive approach to reduce overhead and administrative costs. The author identifies six themes related to successful value improvement efforts and provides examples of successful strategies used by AMCs and their university neighbors to improve the overall value of their programs. He concludes by encouraging leaders of AMCs and universities to share information about their successes in value improvements with each other, to seek additional joint value enhancement efforts, and to market their value improvements to the public. PMID- 26266462 TI - Making Value-Based Payment Work for Academic Health Centers. AB - Under fee-for-service payment systems, physicians and hospitals can be financially harmed by delivering higher-quality, more efficient care. The author describes how current "value-based purchasing" initiatives fail to address the underlying problems in fee-for-service payment and can be particularly problematic for academic health centers (AHCs). Bundled payments, warranties, and condition-based payments can correct the problems with fee-for-service payments and enable physicians and hospitals to redesign care delivery without causing financial problems for themselves. However, the author explains several specific actions that are needed to ensure that payment reforms can be a "win-win-win" for patients, purchasers, and AHCs: (1) disconnecting funding for teaching and research from payment for service delivery, (2) providing predictable payment for essential hospital services, (3) improving the quality and efficiency of care at AHCs, and (4) supporting collaborative relationships between AHCs and community providers by allowing each to focus on their unique strengths and by paying AHC specialists to assist community providers in diagnosis and treatment. With appropriate payment reforms and a commitment by AHCs to redesign care delivery, medical education, and research, AHCs could provide the leadership needed to improve care for patients, lower costs for health care purchasers, and maintain the financial viability of both AHCs and community providers. PMID- 26266461 TI - The Creation of Standard-Setting Videos to Support Faculty Observations of Learner Performance and Entrustment Decisions. AB - Entrustable professional activities (EPAs) provide a framework to standardize medical education outcomes and advance competency-based assessment. Direct observation of performance plays a central role in entrustment decisions; however, data obtained from these observations are often insufficient to draw valid high-stakes conclusions. One approach to enhancing the reliability and validity of these assessments is to create videos that establish performance standards to train faculty observers. Little is known about how to create videos that can serve as standards for assessment of EPAs.The authors report their experience developing videos that represent five levels of performance for an EPA for patient handoffs. The authors describe a process that begins with mapping the EPA to the critical competencies needed to make an entrustment decision. Each competency is then defined by five milestones (behavioral descriptors of performance at five advancing levels). Integration of the milestones at each level across competencies enabled the creation of clinical vignettes that were converted into video scripts and ultimately videos. Each video represented a performance standard from novice to expert. The process included multiple assessments by experts to guide iterative improvements, provide evidence of content validity, and ensure that the authors successfully translated behavioral descriptions and vignettes into videos that represented the intended performance level for a learner. The steps outlined are generalizable to other EPAs, serving as a guide for others to develop videos to train faculty. This process provides the level of content validity evidence necessary to support using videos as standards for high-stakes entrustment decisions. PMID- 26266463 TI - Interweaving Curriculum Committees: A New Structure to Facilitate Oversight and Sustain Innovation. AB - Undergraduate medical education curricula have increased in complexity over the past 25 years; however, the structures for administrative oversight of those curricula remain static. Although expectations for central oversight of medical school curricula have increased, individual academic departments often expect to exert control over the faculty and courses that are supported by the department. The structure of a governance committee in any organization can aid or inhibit that organization's functioning. In 2013, following a major curriculum change in 2007, the Emory University School of Medicine (EUSOM) implemented an "interwoven" configuration for its curriculum committee to better oversee the integrated curriculum. The new curriculum committee structure involves a small executive committee and 10 subcommittees. Each subcommittee performs a specific task or oversees one element of the curriculum. Members, including students, are appointed to two subcommittees in a way that each subcommittee is composed of representatives from multiple other subcommittees. This interweaving facilitates communication between subcommittees and also encourages members to become experts in specific tasks while retaining a comprehensive perspective on student outcomes. EUSOM's previous structure of a single committee with members representing individual departments did not promote cohesive management. The interwoven structure aligns neatly with the goals of the integrated curriculum. Since the restructuring, subcommittee members have been engaged in discussions and decisions on many key issues and expressed satisfaction with the format. The new structure corresponds to EUSOM's educational goals, although the long-term impact on student outcomes still needs to be assessed. PMID- 26266464 TI - The Merits and Challenges of Three-Year Medical School Curricula: Time for an Evidence-Based Discussion. AB - The debate about three-year medical school curricula has resurfaced recently, driven by rising education debt burden and a predicted physician shortage. In this Perspective, the authors call for an evidence-based discussion of the merits and challenges of three-year curricula. They examine published evidence that suggests that three-year curricula are viable, including studies on three-year curricula in (1) U.S. medical schools in the 1970s and 1980s, (2) two Canadian medical schools with more than four decades of experience with such curricula, and (3) accelerated family medicine and internal medicine programs. They also briefly describe the new three-year programs that are being implemented at eight U.S. medical schools, including their own. Finally, they offer suggestions regarding how to enhance the discussion between the proponents of and those with concerns about three-year curricula. PMID- 26266465 TI - Pharmaceutical Role Expansion and Developments in Pharmacist-Physician Communication. AB - Expanded clinical pharmacist professional roles in the team-based patient centered medical home (PCMH) primary care environment require cooperative and collaborative relationships among pharmacists and primary care physicians (PCPs), but many PCPs have not previously worked in such a direct fashion with pharmacists. Additional roles, including formulary control, add further elements of complexity to the clinical pharmacist-PCP relationship that are not well described. Our objective was to characterize the nature of clinical pharmacist PCP interprofessional collaboration across seven federally funded hospitals and associated primary care clinics, following pharmacist placement in primary care clinics and incorporation of expanded pharmacist roles. In-depth and semistructured interviews were conducted with 25 practicing clinical pharmacists and 17 PCPs. Qualitative thematic analysis revealed three major themes: (1) the complexities of electronic communication (particularly electronic nonformulary requests) as contributing to interprofessional tensions or misunderstandings for both groups, (2) the navigation of new roles and traditional hierarchy, with pharmacists using indirect communication to prevent PCP defensiveness to recommendations, and (3) a preference for onsite colocation for enhanced communication and professional relationships. Clinical pharmacists' indirect communication practices may hold important implications for patient safety in the context of medication use, and it is important to foster effective communication skills and an environment where all team members across hierarchies can feel comfortable speaking up to reduce error when problems are suspected. Also, the lack of institutional communication about managing drug formulary issues and related electronic nonformulary request processes was apparent in this study and merits further attention for both researchers and practitioners. PMID- 26266466 TI - Maternal Psychological Control, Use of Supportive Parenting, and Childhood Depressive Symptoms. AB - The current study, operating from a stress-process framework, examined the interactive effects of supportive parenting practices (i.e., mothers' use of positive communication, positive parenting, and parental involvement) and maternal psychological control on mother- and child-reported child depressive symptoms in a community-recruited sample of 9-12 year-olds. Discrepancies between reports of depressive symptoms were also examined. Maternal psychological control was uniquely associated with child-, not mother-, reported depressive symptoms. Parental involvement was uniquely associated with mother-, not child-, reported depressive symptoms. Positive parent-child communication was associated with both reports of child depressive symptoms at the bivariate level, but not when unique associations were examined. Positive parenting was unrelated to either report of depressive symptoms. No interaction effects were detected. The current findings highlight the differential importance of parenting practices on child depressive symptoms, and also indicate the necessity of gathering both parent and child reports of symptomatology and family functioning. PMID- 26266467 TI - The Association Between Socioeconomic Disadvantage and Attention Deficit/Hyperactivity Disorder (ADHD): A Systematic Review. AB - This systematic review examines associations between parental socioeconomic disadvantage and childhood attention deficit/hyperactivity disorder (ADHD). Socioeconomic status (SES) was measured by parental income, education, occupation and marital status. Results were mixed by measure of SES with no one aspect being differentially related to ADHD. 42 studies were included in the review, of which 35 found a significant univariate association between socioeconomic disadvantage and ADHD. Meta-analyses of dimensions of SES and their association with ADHD indicate that children in families of low SES are on average 1.85-2.21 more likely to have ADHD than their peers in high SES families. In spite of substantial between-study heterogeneity, there is evidence for an association between socioeconomic disadvantage and risk of ADHD measured in different ways. This is likely mediated by factors linked to low SES such as parental mental health and maternal smoking during pregnancy. PMID- 26266468 TI - Ilizarov bone transport as a treatment of congenital pseudarthrosis of the tibia: a long-term follow-up study. AB - PURPOSE: Most studies on congenital pseudarthrosis of the tibia (CPT) report on the short-term union rate and refracture rate but do not take into account the long-term outcome. This review includes patients treated with an Ilizarov bone transport, who all reached skeletal maturity. It describes long-term results and highlights any prognostic factors that could predict the final outcome. METHODS: The records of patients with CPT treated with an Ilizarov bone transport in our institution were retrospectively evaluated. RESULTS: A total of 12 consecutive patients were studied. The mean follow-up was 24.5 years (range 6-39 years). Primary consolidation was seen in ten patients (83 %). Half of these patients had a refracture. At final follow-up, eight patients experienced union and four remained un-united, of whom one had an amputation. CONCLUSIONS: The present data confirm a good primary healing rate. However, tibial union at final follow-up was only seen in 67 %, indicating that refracture is the main issue. United bone is often of inferior biological and mechanical quality, so lifetime protection with intramedullary devices, braces or a combination of both is recommended. PMID- 26266469 TI - Two-photon absorption properties and (1)O2 generation ability of Ir complexes: an unexpected large cross section of [Ir(CO)2Cl(4-(para-di-n butylaminostyryl)pyridine)]. AB - The new complexes cis-[Ir(CO)2Cl(4-(para-di-n-butylaminostyryl)pyridine)] () and [Ir(cyclometallated-2-phenylpyridine)2(4,4'-(para-di-n-butylaminostyryl)-2,2' bipyridine)][PF6] () were synthesized and fully characterized along with the known complex Ir(cyclometallated-2-phenylpyridine)2(5-Me-1,10 phenanthroline)][PF6] (). Remarkably, complex , with an Ir(i) centre, displays fluorescence - as opposed to the phosphorescence typical of many Ir(iii) complexes - with a modestly high quantum yield in solution, opening a new route for the design of iridium-based emitters which should not be limited to the +3 oxidation state. It is also characterized by an unexpectedly large two-photon absorption (TPA) cross section, an order of magnitude higher than that previously reported for Ir(iii) or Pt(ii) complexes. The great potential of cyclometallated Ir(iii) complexes for photodynamic therapy was confirmed, with and showing a good singlet oxygen generation ability, coupled with a modest TPA activity for . PMID- 26266470 TI - Disseminated Cutaneous Cytomegalovirus Infection Following Total Body Electron Beam Irradiation for Mycosis Fungoides. PMID- 26266471 TI - [Education and continuing education - modern media for teaching and continuing education in surgery]. PMID- 26266472 TI - [Hand amputation - what is loss of a hand worth?]. PMID- 26266473 TI - [Inguinal Hernia Repair According to Desarda - Implementation of a Mesh-Free Method in a German University Hospital]. AB - Inguinal hernia repair shows a clear tendency towards mesh-based as well as laparoscopic approaches. This is widely reflected in data-based statistics and guidelines. In contrast we have initiated and hereby illustrate the surgical method according to Desarda using autologous fascia to repair inguinal hernia. PMID- 26266474 TI - [Editorial]. PMID- 26266475 TI - [Economic Analysis of Treatment Courses for Patients Over the Age of 80 Years at a Surgical Maximum Care Centre]. AB - BACKGROUND: The demographic change in Germany with an aging population and the resulting necessity of adequate surgical care for older patients was lately discussed with concern. One major aspect is the estimated higher treatment costs in the care of the elderly. MATERIALS AND METHODS: InEK data from all cases of patients over the age of 80, who were treated and discharged from 2008 to 2012 as inpatients at the Department of General, Visceral, Vascular and Thoracic Surgery at the Charite - Universitatsmedizin Berlin, Campus Mitte, were analysed. Of a total of 13,612 patients 626 patients were over the age of 80. Their lengths of stay, mode of discharge and discharge management as well as costs and reimbursements according to the relevant diagnosis-related groups were analysed. RESULTS: Cases of elderly patients amounted to a stable 5 % of all cases from 2008 until 2012. Their mean length of stay was 14 (median, 9), range, 1-129 days. 80 % of patients could be regularly discharged, 9 % died, 8 % were transferred to another hospital, 2 % discharged into a nursing home and 1 % into a rehabilitation centre. The elderly patients had a patient clinical complexity level of mean 2.84. Costs per day amounted to a mean 778 (median: 627) ?, range: 306-7740 ?, total costs to 10,686 (median: 5140) ?, range: 368-186,059 ?. The mean deficit was 491 (median: 176) ? per patient, range: - 30,470-75,144 ?. The discharge management was significantly different in comparison to patients under the age of 80 with respect to avoidance of discharge at the weekend. CONCLUSION: Patients over the age of 80 are a relevant group in surgery. They have an increased perioperative risk, but patients should not be denied surgery solely because of their age. The perioperative management of the elderly has to be of maximum standardised quality. From an economic perspective it can be stated that elderly patients currently pose no exceptional financial risk to a surgical department, but contribute relevantly to the turnover, whereby special attention has to be paid to an early structured discharge management. PMID- 26266476 TI - Median lethal concentration of formaldehyde and its genotoxic potential in bullfrog tadpoles (Lithobates catesbeianus). AB - In order to avoid that contaminated frog farms animals escaping in the environment and become potential vector of emergent diseases, studies with disinfection protocol are strictly necessary. The formaldehyde is one of the compounds tested in fungal disinfection protocols and also used in aquaculture. This study aimed to determine the median lethal concentration (LC50-96h) of formaldehyde in bullfrog tadpoles and to evaluate the possible genotoxic effects in acute exposition. Accordingly, the animals were exposed to formaldehyde in the concentrations of 6, 9, 12, 15, and 18 mg L(-1), and after 96 h blood samples were drawn for the micronucleus (MN) test. The LC50-96h was 10.53 mg L(-1), and the MN frequency increased in proportion to the formaldehyde concentrations, with an estimated frequency in the negative control being 1.35 MN/individual. We concluded that formaldehyde is genotoxic to tadpoles of bullfrogs in the tested concentrations, and the choice of this chemical should be contemplated before its use in animals in captivity. PMID- 26266477 TI - The Moderating Role of English Proficiency in the Association Between Immigrant Chinese Mothers' Authoritative Parenting and Children's Outcomes. AB - The authors' objective was to investigate the association between Chinese immigrant mothers' authoritative parenting and their children's socioemotional and behavioral difficulties. Participants were 136 first-generation Chinese immigrant mothers with 3-5-year-old children residing in the United States. Authoritative parenting was associated with lower socioemotional and behavioral difficulties in children as reported by preschool teachers. Further moderation analyses revealed that immigrant mothers' English proficiency moderated the association between authoritative parenting and children's difficulties. Specifically, authoritative parenting was significantly associated with fewer total difficulties only for children with mothers who reported higher English proficiency. PMID- 26266478 TI - Ethical principles and standards for the conduct of biomedical research and publication. PMID- 26266479 TI - Obstructive sleep apnoea and dementia: is there a link? AB - OBJECTIVE: Obstructive sleep apnoea is a common sleep disturbance in people of all ages, while dementia is an increasing entity among the ageing population of the world. Recent studies have established a link between sleep apnoea and cognitive decline. This literature review explores this relationship and examines the mechanisms, neurobiology and treatment modalities. DESIGN: The study was conducted with the use of narrative literature overview. RESULTS AND CONCLUSIONS: While there are numerous studies that establish a clear relationship between obstructive sleep apnoea, cognitive decline and dementia, more work is needed in understanding the mechanism and processes involved. A detailed understanding of pathophysiology of sleep and the relationship with cognitive decline will be vital in addressing the possibility of averting a likely reversible cause of dementia or cognitive decline. PMID- 26266480 TI - Effective Bone Regeneration Using Thermosensitive Poly(N-Isopropylacrylamide) Grafted Gelatin as Injectable Carrier for Bone Mesenchymal Stem Cells. AB - In this study, thermosensitive poly(N-isopropylacrylamide) (PNIPAAm) was grafted onto gelatin via atom transfer radical polymerization (ATRP). The chemical structure of PNIPAAm-grafted gelatin (Gel-PNIPAAm) was confirmed by XPS, ATR-IR, and (1)H NMR characterizations. Gel-PNIPAAm aqueous solution exhibited sol-to-gel transformation at physiological temperature, and was studied as injectable hydrogel for bone defect regeneration in a cranial model. The hydrogel was biocompatible and demonstrated the ability to enhance bone regeneration in comparison with the untreated group (control). With the incorporation of rat bone mesenchymal stem cells (BMSCs) into the hydrogel, the bone regeneration rate was further significantly enhanced. As indicated by micro-CT, histological (H&E and Masson) and immunohistochemical (osteocalcin and osteopontin) staining, newly formed woven bone tissue was clearly detected at 12 weeks postimplantation in the hydrogel/BMSCs treated group, showing indistinguishable boundary with surrounding host bone tissues. The results suggested that the thermosensitive Gel-PNIPAAm hydrogel was an excellent injectable delivery vehicle of BMSCs for in vivo bone defect regeneration. PMID- 26266481 TI - Forecasting methodologies for Ganoderma spore concentration using combined statistical approaches and model evaluations. AB - High concentration levels of Ganoderma spp. spores were observed in Worcester, UK, during 2006-2010. These basidiospores are known to cause sensitization due to the allergen content and their small dimensions. This enables them to penetrate the lower part of the respiratory tract in humans. Establishment of a link between occurring symptoms of sensitization to Ganoderma spp. and other basidiospores is challenging due to lack of information regarding spore concentration in the air. Hence, aerobiological monitoring should be conducted, and if possible extended with the construction of forecast models. Daily mean concentration of allergenic Ganoderma spp. spores in the atmosphere of Worcester was measured using 7-day volumetric spore sampler through five consecutive years. The relationships between the presence of spores in the air and the weather parameters were examined. Forecast models were constructed for Ganoderma spp. spores using advanced statistical techniques, i.e. multivariate regression trees and artificial neural networks. Dew point temperature along with maximum temperature was the most important factor influencing the presence of spores in the air of Worcester. Based on these two major factors and several others of lesser importance, thresholds for certain levels of fungal spore concentration, i.e. low (0-49 s m(-3)), moderate (50-99 s m(-3)), high (100-149 s m(-3)) and very high (150 < n s m(-3)), could be designated. Despite some deviation in results obtained by artificial neural networks, authors have achieved a forecasting model, which was accurate (correlation between observed and predicted values varied from r s = 0.57 to r s = 0.68). PMID- 26266482 TI - Effect of passive heat stress on arterial stiffness in smokers versus non smokers. AB - In non-smokers, passive heat stress increases shear stress and vasodilation, decreasing arterial stiffness. Smokers, who reportedly have arterial dysfunction, may have similar improvements in arterial stiffness with passive heat stress. Therefore, we examined the effects of an acute bout of whole-body passive heat stress on arterial stiffness in smokers vs. non-smokers. Thirteen smokers (8.8 +/ 5.5 [median = 6] cigarettes per day for > 4 years) and 13 non-smokers matched for age, mass, height, and exercise habits (27 +/- 8 years; 78.8 +/- 15.4 kg; 177.6 +/- 6.7 cm) were passively heated to 1.5 degrees C core temperature (T C) increase. At baseline and each 0.5 degrees C T C increase, peripheral (pPWV) and central pulse wave velocity (cPWV) were measured via Doppler ultrasound. No differences existed between smokers and non-smokers for any variables (all p > .05), except cPWV slightly increased from baseline (526.7 +/- 81.7 cm . s(-1)) to 1.5 degrees C DeltaT C (579.7 +/- 69.8 cm . s(-1); p < 0.005), suggesting heat stress acutely increased central arterial stiffness. pPWV did not change with heating (grand mean: baseline = 691.9 +/- 92.9 cm . s(-1); 1.5 degrees C DeltaT C = 691.9 +/- 79.5 cm . s(-1); p > 0.05). Changes in cPWV and pPWV during heating correlated (p < 0.05) with baseline PWV in smokers (cPWV: r = -0.59; pPWV: r = 0.62) and non-smokers (cPWV: r = -0.45; pPWV: r = -0.77). Independent of smoking status, baseline stiffness appears to mediate the magnitude of heating-induced changes in arterial stiffness. PMID- 26266483 TI - Relationships of self-identified cold tolerance and cold-induced vasodilatation in the finger. AB - This study was conducted to investigate relationships of self-identified cold tolerance and cold-induced vasodilatation (CIVD) in the finger. Nine males and 34 females participated in the following 2 tests: a CIVD test and a self-reported survey. The CIVD test was conducted 30-min cold-water immersion (3.8 +/- 0.3 degrees C) of the middle finger at an air temperature of 27.9 +/- 0.1 degrees C. The self-reported questionnaire consisted of 28 questions about whole and local body cold and heat tolerances. By a cluster analysis on the survey results, the participants were divided into two groups: high self-identified cold tolerance (HSCT, n = 25) and low self-identified cold tolerance (LSCT, n = 18). LSCT had lower self-identified cold tolerance (P < 0.001), preferred hot thermal stimulation (P = 0.006), and wore heavier clothing during daily life (P < 0.001) than HSCT. LSCT had significantly lower maximal finger temperatures (T max) (P = 0.040), smaller amplitude (P = 0.029), and delayed onset time of CIVD (P = 0.080) when compared to HSCT. Some questions examining the self-identified cold or heat tolerance had relationships with cold tolerance index, T max, and amplitude (P < 0.1). These results indicate that self-identified cold tolerance classified through a standardized survey could be a good index to predict physiological cold tolerance. PMID- 26266484 TI - Ethnic and geographic variations in HPV prevalence and genotype distribution in north-western Yunnan, China. AB - The prevalence and genotype distribution of human papillomavirus (HPV) vary throughout the world. To assess the prevalence and genotype distribution of HPV among three ethnic groups in two geographic locations in north-western Yunnan, we recruited 522 women in Shangri-le (n = 255) and Lijiang (n = 267). PCR amplification of HPV DNA was performed on cervical cells from these women using two consensus primer systems (MY09/11 and GP5/6). Amplified-HPV DNA was genotyped using the HPV GenoArray test. Geographically, the HPV prevalence was significantly higher (P = 0.002) among Shangri-le women than among Lijiang women. Infections with high-risk (HR)-HPV and with multiple HPV genotypes were also significantly more common (P = 0.001) among women in Shangri-le than women in Lijiang. Additionally, the prevalence of overall, HR-HPV, and single genotype HPV infections was significantly higher (P = 0.001) among Tibetan women than among Naxi and Han women. HPV-16 and HPV-33 were significantly more frequent in Shangri le women compared with Lijiang (P = 0.006) women. In addition, HPV-16 (9.81%) and HPV-33 (5.88%) were significantly more prevalent in Tibetan women than in Naxi and Han women. Here, for the first time, we highlight the significant variation in the prevalence and genotype distribution of HPV in various populations in the north-western region of Yunnan Province. PMID- 26266485 TI - A pigmented skin lesion on the back. PMID- 26266486 TI - Expression of Cocaine and Amphetamine Regulated Transcript (CART) in the Porcine Intramural Neurons of Stomach in the Course of Experimentally Induced Diabetes Mellitus. AB - In the present study, the effect of streptozotocin-induced diabetes on the cocaine- and amphetamine-regulated transcript-like immunoreactive (CART-LI) enteric nervous structures was investigated within the porcine stomach. To induce diabetes, the pigs were administered intravenously streptozotocin at a dose of 150 mg/kg of body weight. A significant decrease of the number of CART-LI perikarya was observed in the myenteric plexus of the gastric antrum, corpus, and pylorus in the experimental group. In contrast, submucous plexus was devoid of CART-positive neuronal cells both in control and experimental animals. In the control group, the highest densities of CART-LI nerve fibers were observed in the circular muscle layer of antrum and slightly less nerve fibers were present in the muscle layer of corpus and pylorus. In turn, submucous layer of all studied stomach regions revealed relatively smaller number of CART-positive nerve fibers. Diabetes caused statistically significant decrease in the expression of CART-LI nerve fibers only in the antrum circular muscle layer. Also, no changes in the CART-like immunoreactivity in the intraganglionic nerve fibers were observed. The obtained results suggest that acute hyperglycemia produced significant reduction of the CART expression in enteric perikarya throughout entire stomach as well as decrease of density the CART-LI fibers in circular muscle layer of the antrum. Additionally, we suggest that CART might be involved in the regulation of stomach function especially in the gastric motility. PMID- 26266487 TI - The Interplay of Akt and ERK in Abeta Toxicity and Insulin-Mediated Protection in Primary Hippocampal Cell Culture. AB - It is not known if insulin prevents Abeta-induced cell death, MAPK, and Akt activity in isolated hippocampal cell culture. This study was aimed to explore the effect of insulin on Abeta-induced cell death and ERK and Akt signaling alteration in isolated hippocampal cell culture. Additionally, it was desirable to assess if there is any interaction between these two pathways. The hippocampal cells were derived from fetuses at the embryonic day 18-19. The cells were treated with different drugs, and MTT assay, morphological assessments, and Western blot were done. Insulin prevented Abeta-induced cell death and caspase-3 cleavage. Abeta-induced toxicity was aligned with decrement of the phosphorylated Akt (pAkt) which was prevented by insulin. The PI3 kinase inhibitor, LY294002, decreased pAkt and abolished the protective effect of insulin. Abeta exposure increased phosphorylated ERK (pERK) in parallel with cell death and apoptosis. Insulin-inhibited ERK activation (phosphorylation) induced by Abeta and PD98059 (as ERK inhibitor) did not affect the protective effect of insulin. One of the interesting finding of this study was the interplay of Akt and ERK in Abeta toxicity and insulin-mediated protection; meaning that there is an inverse relation between pERK and pAkt, in a way that PI3-Akt pathway inhibition leads to pERK increment while ERK inhibition causes Akt phosphorylation (activation). This study showed, for the first time, that insulin protects against Abeta toxicity in isolated hippocampal cell culture via modulating Akt and ERK phosphorylation and also revealed an interaction between those signals in Abeta toxicity and insulin mediated protection. PMID- 26266488 TI - TCTP Expression After Rat Spinal Cord Injury: Implications for Astrocyte Proliferation and Migration. AB - Translationally controlled tumor protein (TCTP) is a ubiquitous and highly conserved protein which plays a role in cell proliferation and growth, apoptosis, and cell cycle regulation. However, its expression and function in spinal cord injury (SCI) are still unknown. Here, we demonstrated that expression of TCTP was dynamic changed after acute spinal cord injury. Our results showed that TCTP gradually increased, reached a peak at 3 day, and then declined to basal levels at 14 days after spinal cord injury. Upregulation of TCTP was accompanied with an increase in the levels of proliferation proteins such as PCNA. Immunofluorescent labeling also showed that TCTP located in astrocytes and traumatic SCI induced TCTP colocalizated with PCNA. These results indicated that TCTP might play an important role in astrocyte proliferation. To further probe the role of TCTP, TCTP-specific siRNA-transfected astrocytes showed significant decrease of primary astrocyte proliferation. Surprisingly, TCTP knockdown also reduced primary astrocyte migration, as the reorganization of microtubules and F-actin was disturbed after siRNA transfection. All above indicated that TCTP might play a crucial role in astrocyte proliferation and migration. Collectively, our data suggested that TCTP might play important roles in CNS pathophysiology after SCI. PMID- 26266489 TI - Assessment of the utility of contact-based restraints in accelerating the prediction of protein structure using molecular dynamics simulations. AB - Molecular dynamics (MD) simulation is a well-established tool for the computational study of protein structure and dynamics, but its application to the important problem of protein structure prediction remains challenging, in part because extremely long timescales can be required to reach the native structure. Here, we examine the extent to which the use of low-resolution information in the form of residue-residue contacts, which can often be inferred from bioinformatics or experimental studies, can accelerate the determination of protein structure in simulation. We incorporated sets of 62, 31, or 15 contact-based restraints in MD simulations of ubiquitin, a benchmark system known to fold to the native state on the millisecond timescale in unrestrained simulations. One-third of the restrained simulations folded to the native state within a few tens of microseconds-a speedup of over an order of magnitude compared with unrestrained simulations and a demonstration of the potential for limited amounts of structural information to accelerate structure determination. Almost all of the remaining ubiquitin simulations reached near-native conformations within a few tens of microseconds, but remained trapped there, apparently due to the restraints. We discuss potential methodological improvements that would facilitate escape from these near-native traps and allow more simulations to quickly reach the native state. Finally, using a target from the Critical Assessment of protein Structure Prediction (CASP) experiment, we show that distance restraints can improve simulation accuracy: In our simulations, restraints stabilized the native state of the protein, enabling a reasonable structural model to be inferred. PMID- 26266491 TI - Electron-Transport Properties of Few-Layer Black Phosphorus. AB - We perform the first-principles computational study of the effect of number of stacking layers and stacking style of the few-layer black phosphorus (BPs) on the electronic properties, including transport gap, current-voltage (i-v) relation, and differential conductance. Our computation is based on the nonequilibrium Green's function approach combined with density functional theory calculations. Specifically, we compute electron-transport properties of monolayer BP, bilayer BP, and trilayer BP as well as bilayer BPs with AB-, AA-, or AC-stacking. We find that the stacking number has greater influence on the transport gap than the stacking type. Conversely, the stacking type has greater influence on i-v curve and differential conductance than on the transport gap. This study offers useful guidance for determining the number of stacking layers and the stacking style of few-layer BP sheets in future experimental measurements and for potential applications in nanoelectronic devices. PMID- 26266490 TI - Widening the Product Profile of Carbon Dioxide Reduction by Vanadium Nitrogenase. AB - Two reaction systems based on vanadium nitrogenase were previously shown to reduce CO2 to hydrocarbons: 1) an enzyme-based system that used both components of V nitrogenase for ATP-dependent reduction of CO2 to <=C2 hydrocarbons; and 2) a cofactor-based system that employed SmI2 to supply electrons to the isolated V cluster for an ATP-independent reduction of CO2 to <=C3 hydrocarbons. Here, we report ATP-independent reduction of CO2 to hydrocarbons by a reaction system comprising Eu(II) DTPA and the VFe protein of V nitrogenase. Combining features of both enzyme- and cofactor-based systems, this system exhibits improved C-C coupling and a broader product profile of <=C4 hydrocarbons. The C-C coupling does not employ CO2 -derived CO, and it is significantly enhanced in D2 O. These observations afford initial insights into the characteristics of this unique reaction and provide a potential template for future design of catalysts to recycle the greenhouse gas CO2 into useful products. PMID- 26266493 TI - Liquid-Liquid Phase Transition and Its Phase Diagram in Deeply-Cooled Heavy Water Confined in a Nanoporous Silica Matrix. AB - Using neutron diffraction technique, we measure the average density of the heavy water confined in a nanoporous silica matrix, MCM-41, over the pressure temperature plane. The result suggests the existence of a line of liquid-liquid phase transition with its end point at 1.29 +/- 0.34 kbar and 213 +/- 3 K in a fully hydrated sample. This point would be the liquid-liquid critical point (LLCP) according to the "liquid-liquid critical point" scenario. The phase diagram of the deeply cooled confined heavy water is then discussed. Moreover, in a partially hydrated sample, the phase transition completely disappears. This result shows that it is the free water part, rather than the bound water part, of the confined water that undergoes a liquid-liquid transition. PMID- 26266492 TI - Residual CTAB Ligands as Mass Spectrometry Labels to Monitor Cellular Uptake of Au Nanorods. AB - Gold nanorods have numerous applications in biomedical research, including diagnostics, bioimaging, and photothermal therapy. Even though surfactant removal and surface conjugation with antifouling molecules such as polyethylene glycol (PEG) are required to minimize nonspecific protein binding and cell uptake, the reliable characterization of these processes remains challenging. We propose here the use of laser desorption/ionization mass spectrometry (LDI-MS) to study the ligand exchange efficiency of cetyltrimethylammonium bromide (CTAB)-coated nanorods with different PEG grafting densities and to characterize nanorod internalization in cells. Application of LDI-MS analysis shows that residual CTAB consistently remains adsorbed on PEG-capped Au nanorods. Interestingly, such residual CTAB can be exploited as a mass barcode to discern the presence of nanorods in complex fluids and in vitro cellular systems, even at very low concentrations. PMID- 26266494 TI - Surface Plasmon-Coupled Directional Enhanced Raman Scattering by Means of the Reverse Kretschmann Configuration. AB - Surface-enhanced Raman scattering (SERS) is a unique analytical technique that provides fingerprint spectra, yet facing the obstacle of low collection efficiency. In this study, we demonstrated a simple approach to measure surface plasmon-coupled directional enhanced Raman scattering by means of the reverse Kretschmann configuration (RK-SPCR). Highly directional and p-polarized Raman scattering of 4-aminothiophenol (4-ATP) was observed on a nanoparticle-on-film substrate at 46 degrees through the prism coupler with a sharp angle distribution (full width at half-maximum of ~3.3 degrees ). Because of the improved collection efficiency, the Raman scattering signal was enhanced 30-fold over the conventional SERS mode; this was consistent with finite-difference time domain simulations. The effect of nanoparticles on the coupling efficiency of propagated surface plasmons was investigated. Possessing straightforward implementation and directional enhancement of Raman scattering, RK-SPCR is anticipated to simplify SERS instruments and to be broadly applicable to biochemical assays. PMID- 26266495 TI - The "Metric" System: Yet More Chaos in Scholarly Publishing. PMID- 26266496 TI - Neither Two-State nor Three-State: Dimerization of Lambda Cro Repressor. AB - Lambda Cro repressor is one of the best studied dimeric transcription factors. However, there has still been an unsettled debate for decades about whether it is a two-state dimer or three-state dimer. We provide a new mechanism model that can reconcile these seemingly conflicting (mutually exclusive) experimental results. From simulations with all-atom structure-based model, we observe that the dimerization process of Lambda Cro repressor starts from one folded monomer with one unfolded monomer. Intrasubunit folding and intersubunit binding are partially coupled, in a fly casting manner. PMID- 26266497 TI - Electronic Structure of Sodium Superoxide Bulk, (100) Surface, and Clusters using Hybrid Density Functional: Relevance for Na-O2 Batteries. AB - Clarifying the electronic structure of sodium superoxide (NaO2) is a key step in understanding the electrochemical behavior of Na-O2 batteries. Here we report a density functional theory study to explore the effect of atomic structure and morphology on the electronic properties of different model systems: NaO2 bulk, (100) surface, and small (NaO2)n clusters (n = 3-8). We found that a correct description of the open-shell 2p electrons of O2(-) requires the use of a hybrid functional, which reveals a clear insulating nature of all of the investigated systems. This sheds light onto the capacity limitations of pure NaO2 as a discharge product and highlights the need for developing new strategies to enhance its electron transport in the optimization of Na-O2 cells. PMID- 26266498 TI - Theoretical Insights into a CO Dimerization Mechanism in CO2 Electroreduction. AB - In this work, we present DFT simulations that demonstrate the ability of Cu to catalyze CO dimerization in CO2 and CO electroreduction. We describe a previously unreported CO dimer configuration that is uniquely stabilized by a charged water layer on both Cu(111) and Cu(100). Without this charged water layer at the metal surface, the formation of the CO dimer is prohibitively endergonic. Our calculations also demonstrate that dimerization should have a lower activation barrier on Cu(100) than Cu(111), which, along with a more exergonic adsorption energy and a corresponding higher coverage of *CO, is consistent with experimental observations that Cu(100) has a high activity for C-C coupling at low overpotentials. We also demonstrate that this effect is present with cations other than H(+), a finding that is consistent with the experimentally observed pH independence of C2 formation on Cu. PMID- 26266499 TI - Evolution of Hydrogen Dynamics in Amorphous Ice with Density. AB - The single-particle dynamics of hydrogen atoms in several of the amorphous ices are reported using a combination of deep inelastic neutron scattering (DINS) and inelastic neutron scattering (INS). The mean kinetic energies of the hydrogen nuclei are found to increase with increasing density, indicating the weakening of hydrogen bonds as well as a trend toward steeper and more harmonic hydrogen vibrational potential energy surfaces. DINS shows much more pronounced changes in the O-H stretching component of the mean kinetic energy going from low- to high density amorphous ices than indicated by INS and Raman spectroscopy. This highlights the power of the DINS technique to retrieve accurate ground-state kinetic energies beyond the harmonic approximation. In a novel approach, we use information from DINS and INS to determine the anharmonicity constants of the O-H stretching modes. Furthermore, our experimental kinetic energies will serve as important benchmark values for path-integral Monte Carlo simulations. PMID- 26266500 TI - Single-Particle Spectroscopic Study on Fluorescence Enhancement by Plasmon Coupled Gold Nanorod Dimers Assembled on DNA Origami. AB - Metal-enhanced fluorescence has attracted much attention due to its scientific importance and lots of potential applications. Plasmon coupled metal nanoparticles have been demonstrated to further improve the enhancement effects. Conventional studies of metal-enhanced fluorescence on the bulk systems are complicated by the ensemble average effects over many critical factors with large variations. Here, fluorescence enhancement of ATTO-655 by a plasmon coupled gold nanorod dimer fixed on a DNA origami nanobreadboard was studied on the single particle level. A series of gold nanorod dimers with linear orientation and different gap distances ranging from 6.1 to 26.0 nm were investigated to explore the plasmon coupling effect on fluorescence enhancement. The results show that the dimer with the smallest gap (6.1 nm) gives the highest enhancement (470 fold), and the enhancement gradually decreases as the gap distance increases and eventually approaches that from a monomer (120-fold). This trend is consistent with the numerical calculation results. This study indicates that plasmon coupling in gold nanorod dimers offers further increased excitation efficiency to achieve large fluorescence enhancement. PMID- 26266501 TI - Critical Au Concentration for the Stabilization of Au-Cu Nanoparticles on Rutile against Dissociation under Oxygen. AB - Controlling aging of catalysts is of crucial importance to preserve their properties, in particular for bimetallic nanoparticles (NPs) where reaction can modify the composition. Herein, we have studied the stability upon oxygen exposure of gold-copper NPs supported on rutile. We have used in situ scanning tunneling microscopy to follow the evolution of individual Au, Cu and Au-Cu NPs with various compositions grown on the TiO2(110) surface, during each step from their nucleation to their modification with oxygen. We demonstrated a direct relation between the stability of the nanoparticles and their Au concentration. Whereas pure Cu nanoparticles dissociate under O2, Au-Cu NPs containing at least 20% Au are stable. This is explained by a modification of the local density of states of Cu atoms upon alloying. PMID- 26266502 TI - Directed Assembly of Optoplasmonic Hybrid Materials with Tunable Photonic Plasmonic Properties. AB - Optoplasmonic materials are metallo-dielectric hybrid structures that combine metallic and dielectric components in defined geometries in which plasmonic and photonic modes synergistically interact. These beneficial interactions can be harnessed by integrating plasmonic nanoantennas into defined photonic environments generated, for instance, by discrete optical resonators or extended systems of diffractively coupled nanoparticles. Optoplasmonic structures facilitate photonic-plasmonic mode coupling and offer degrees of freedom for creating optical fields with predefined amplitude and phase in space and time that are absent in conventional photonic or plasmonic structures. This Perspective reviews the fundamental electromagnetic mechanisms underlying selected optoplasmonic approaches with an emphasis on materials available through template-guided self-assembly strategies. PMID- 26266503 TI - Tuning the Flight Length of Molecules Diffusing on a Hydrophobic Surface. AB - Transport at solid-liquid interfaces is critical to self-assembly, biosensing, and heterogeneous catalysis, but surface diffusion remains difficult to characterize and rationally manipulate, due to the inherent heterogeneity of adsorption on solid surfaces. Using single-molecule tracking, we characterized the diffusion of a fluorescent long-chain surfactant on a hydrophobic surface, which involved periods of confinement alternating with bulk-mediated "flights". The concentration of methanol in solution was varied to tune the strength of the hydrophobic surface-molecule interaction. The frequency of confinement had a nonmonotonic dependence on methanol concentration that reflected the relative influence of anomalously strong adsorption sites. By carefully accounting for the effect of this surface heterogeneity, we demonstrated that flight lengths increased monotonically as the hydrophobic attraction decreased, in agreement with theoretical predictions for bulk-mediated surface diffusion. The theory provided an accurate description of surface diffusion, despite the system being heterogeneous, and can be leveraged to optimize molecular search and assembly processes. PMID- 26266505 TI - Band Gap Reduction in ZnO and ZnS by Creating Layered ZnO/ZnS Heterostructures. AB - Wurtzite-type zinc oxide (ZnO) and zinc sulfide (ZnS) have electronic band gaps that are too large for light-harvesting applications. Using screened hybrid density-functional methods, we show that the band gaps of ZnO and ZnS can be dramatically reduced by creating layered ZnO/ZnS bulk heterostructures in which m contiguous monolayers of ZnO alternate with n contiguous monolayers of ZnS. In particular, the band gap decreases by roughly 40% upon substitution of every tenth monolayer of ZnS with a monolayer of ZnO (and vice versa) and becomes as low as 1.5 eV for heterostructures with m = 3 to m = 9 contiguous monolayers of ZnO alternating with n = 10 - m monolayers of ZnS. The predicted band gaps of layered ZnO/ZnS heterostructures span the entire visible spectrum, which makes these materials suitable for photovoltaic device engineering. PMID- 26266504 TI - Ion-Induced Dipole Interactions and Fragmentation Times: Calpha-Cbeta Chromophore Bond Dissociation Channel. AB - The fragmentation times corresponding to the loss of the chromophore (Calpha Cbeta bond dissociation channel) after photoexcitation at 263 nm have been investigated for several small peptides containing tryptophan or tyrosine. For tryptophan-containing peptides, the aromatic chromophore is lost as an ionic fragment (m/z 130), and the fragmentation time increases with the mass of the neutral fragment. In contrast, for tyrosine-containing peptides the aromatic chromophore is always lost as a neutral fragment (mass = 107 amu) and the fragmentation time is found to be fast (<20 ns). These different behaviors are explained by the role of the postfragmentation interaction in the complex formed after the Calpha-Cbeta bond cleavage. PMID- 26266506 TI - Best Practices for Operando Battery Experiments: Influences of X-ray Experiment Design on Observed Electrochemical Reactivity. PMID- 26266507 TI - Multifaceted Excited State of CH3NH3PbI3. Charge Separation, Recombination, and Trapping. AB - A need to understand the excited-state behavior of organic-inorganic hybrid perovskites, such as CH3NH3PbI3, has arisen due to the rapid development of perovskite solar cells. The photoinduced processes leading to the efficient charge separation observed in these materials remain somewhat elusive. This Perspective presents an overview of the initial attempts to characterize the excited-state and charge recombination dynamics in the prototypical material CH3NH3PbI3. While much has been accomplished in designing high-efficiency solar cells, the multifaceted nature of the CH3NH3PbI3 excited state offers ample challenges for the photovoltaic community to better comprehend. Building on this foundation may enable us to tackle the stability concerns that have shadowed the rise of perovskite solar cells. Furthermore, a better understanding of the excited-state properties can provide insight into the specific properties that have thrust this material to the forefront of photovoltaic research. PMID- 26266508 TI - Ultrafast Intersystem-Crossing Dynamics and Breakdown of the Kasha-Vavilov's Rule of Naphthalenediimides. AB - The fluorescence quantum yield of a red naphthalenediimide dye (rNDI) with amino and Br core substituents has been found to decrease by a factor of almost 2 by going from S1 <- S0 to S2 <- S0 excitation. Time-resolved spectroscopic measurements reveal that this deviation from the Kasha-Vavilov's rule is due to an ultrafast, < 200 fs, intersystem-crossing (ISC) from the S2 state to the triplet manifold, due to the pipi* -> npi* character of the transition and to the presence of the heavy Br atom. In non-core substituted naphthalenediimide (pNDI), ISC is slower, ~2 ps, and was found to be reversible on a time scale shorter than that of vibrational cooling. The fluorescence and triplet quantum yields of rNDI, thus, can be substantially changed by a simple variation of the excitation wavelength. PMID- 26266509 TI - Looking Inside the Perchlorinated Trityl Radical/Metal Spinterface through Spectroscopy. AB - We report on a spectroscopic multitechnique approach to study the metal/radical spinterface formed by a perchlorinated trityl radical derivative and either gold or silver. The spectroscopic fingerprint of their paramagnetic properties could be determined by comparison with their diamagnetic precursor and by DFT calculations. Thanks to the presented approach, we could gain unprecedented insight into the radical-metal interaction and how this latter perturbs the spin polarization and consequently the magnetoelectronic properties of the radical adlayer. Knowledge of the factors influencing the spinterface is an essential tool toward the tailoring of the properties of spin-based electronic devices. PMID- 26266510 TI - Discovery of a Missing Link: Detection and Structure of the Elusive Disilicon Carbide Cluster. AB - The rotational spectrum of the elusive but fundamentally important silicon carbide SiCSi has been detected using sensitive microwave techniques aided by high-level ab initio methods. Its equilibrium structure has been determined to very high precision using isotopic substitution and vibrational corrections calculated quantum-chemically: it is an isosceles triangle with a Si-C bond length of 1.693(1) A, and an apex angle of 114.87(5) degrees . Now that all four Si(m)C(n) clusters with m + n = 3 have been observed experimentally, their structure and chemical bonding can be rigorously compared. Because Si2C is so closely linked to other Si-bearing molecules that have been detected in the evolved carbon star IRC+10216, it is an extremely promising candidate for detection with radio telescopes. PMID- 26266511 TI - Photonic-Plasmonic Devices Created by Templated Self-Assembly. PMID- 26266512 TI - Background-Free Fourth-Order Sum Frequency Generation Spectroscopy. AB - The recently developed 2D sum frequency generation spectroscopy offers new possibilities to analyze the structure and structural dynamics of interfaces in a surface-specific manner. Its implementation, however, has so far remained limited to the pump-probe geometry, with its inherent restrictions. Here we present 2D SFG experiments utilizing a novel noncollinear geometry of four incident laser pulses generating a 2D SFG response, analogous to the triangle geometry applied in bulk-sensitive 2D infrared spectroscopy. This approach allows for background free measurements of fourth-order nonlinear signals, which is demonstrated by measuring the fourth-order material response from a GaAs (110) surface. The implementation of phase-sensitive detection and broadband excitation pulses allows for both highest possible time resolution and high spectral resolution of the pump axis of a measured 2D SFG spectrum. To reduce the noise in our spectra, we employ a referencing procedure, for which we use noncollinear pathways and individual focusing for the signal and local oscillator beams. The 2D spectra recorded from the GaAs (110) surface show nonzero responses for the real and imaginary component, pointing to contributions from resonant electronic pathways to the chi((4)) response. PMID- 26266513 TI - Same-View Nano-XAFS/STEM-EDS Imagings of Pt Chemical Species in Pt/C Cathode Catalyst Layers of a Polymer Electrolyte Fuel Cell. AB - We have made the first success in the same-view imagings of 2D nano-XAFS and TEM/STEM-EDS under a humid N2 atmosphere for Pt/C cathode catalyst layers in membrane electrode assemblies (MEAs) of polymer electrolyte fuel cells (PEFCs) with Nafion membrane to examine the degradation of Pt/C cathodes by anode gas exchange cycles (start-up/shut-down simulations of PEFC vehicles). The same-view imaging under the humid N2 atmosphere provided unprecedented spatial information on the distribution of Pt nanoparticles and oxidation states in the Pt/C cathode catalyst layer as well as Nafion ionomer-filled nanoholes of carbon support in the wet MEA, which evidence the origin of the formation of Pt oxidation species and isolated Pt nanoparticles in the nanohole areas of the cathode layer with different Pt/ionomer ratios, relevant to the degradation of PEFC catalysts. PMID- 26266514 TI - Residue-Specific Force Field (RSFF2) Improves the Modeling of Conformational Behavior of Peptides and Proteins. AB - A recent report of (3)J(HNHalpha) scalar coupling constants for hundreds of two residue peptides has provided an important opportunity to test simulation force fields for proteins. Here, we compare the abilities of three derivatives of the Amber ff99SB force field to reproduce these data. We report molecular dynamics (MD) simulations of 256 two-residue peptides and show that the recently developed residue-specific force field (RSFF2) produces a dramatic improvement in the agreement with experimental (3)J(HNHalpha) coupling constants. We further show that RSFF2 also appears to produce a modest improvement in reproducing the (3)J(HNHalpha) coupling constants of five model proteins. Perhaps surprisingly, an analysis of neighboring residue effects (NREs) on the (3)J(HNHalpha) coupling constants of the two-residue peptides indicates little difference between the force fields' abilities to reproduce experimental NREs. We speculate that this might indicate limitations in the force fields' descriptions of nonbonded interactions between adjacent side chains or with terminal capping groups. PMID- 26266515 TI - Transformation of Au144(SCH2CH2Ph)60 to Au133(SPh-tBu)52 Nanomolecules: Theoretical and Experimental Study. AB - Ultrastable gold nanomolecule Au144(SCH2CH2Ph)60 upon etching with excess tert butylbenzenethiol undergoes a core-size conversion and compositional change to form an entirely new core of Au133(SPh-tBu)52. This conversion was studied using high-resolution electrospray mass spectrometry which shows that the core size conversion is initiated after 22 ligand exchanges, suggesting a relatively high stability of the Au144(SCH2CH2Ph)38(SPh-tBu)22 intermediate. The Au144 -> Au133 core size conversion is surprisingly different from the Au144 -> Au99 core conversion reported in the case of thiophenol, -SPh. Theoretical analysis and ab initio molecular dynamics simulations show that rigid p-tBu groups play a crucial role by reducing the cluster structural freedom, and protecting the cluster from adsorption of exogenous and reactive species, thus rationalizing the kinetic factors that stabilize the Au133 core size. This 144-atom to 133-atom nanomolecule's compositional change is reflected in optical spectroscopy and electrochemistry. PMID- 26266516 TI - Angle-Dependent Ionization of Small Molecules by Time-Dependent Configuration Interaction and an Absorbing Potential. AB - The angle-dependence of strong field ionization of O2, N2, CO2, and CH2O has been studied theoretically using a time-dependent configuration interaction approach with a complex absorbing potential (TDCIS-CAP). Calculation of the ionization yields as a function of the direction of polarization of the laser pulse produces three-dimensional surfaces of the angle-dependent ionization probability. These three-dimensional shapes and their variation with laser intensity can be interpreted in terms of ionization from the highest occupied molecular orbital (HOMO) and lower lying orbitals, and the Dyson orbitals for the ground and excited states of the cations. PMID- 26266517 TI - Toward the Ultra-incompressible Carbon Materials. Computational Simulation and Experimental Observation. AB - The common opinion that diamond is the stiffest material is disproved by a number of experimental studies where the fabrication of carbon materials based on polymerized fullerenes with outstanding mechanical stiffness was reported. Here we investigated the nature of this unusual effect. We present a model constituted of compressed polymerized fullerite clusters implemented in a diamond matrix with bulk modulus B0 much higher than that of diamond. The calculated B0 value depends on the sizes of both fullerite grain and diamond environment and shows close correspondence with measured data. Additionally, we provide results of experimental study of atomic structure and mechanical properties of ultrahard carbon material supported the presented model. PMID- 26266518 TI - Highs and Lows in English Attachment. AB - Grillo and Costa (2014) claim that Relative-Clause attachment ambiguity resolution is largely dependent on whether or not a Pseudo-Relative interpretation is available. Data from Italian, and other languages allowing Pseudo-Relatives, support this hypothesis. Pseudo-Relative availability, however, covaries with the semantics of the main predicate (e.g., perceptual vs. stative). Experiment 1 assesses whether this predicate distinction alone can account for prior attachment results by testing it with a language that disallows Pseudo Relatives (i.e. English). Low Attachment was found independent of Predicate-Type. Predicate-Type did however have a minor modulatory role. Experiment 2 shows that English, traditionally classified as a Low Attachment language, can demonstrate High Attachment with sentences globally ambiguous between a Small-Clause and a reduced Relative-Clause interpretation. These results support a grammatical account of previous effects and provide novel evidence for the parser's preference of a Small-Clause over a Restrictive interpretation, crosslinguistically. PMID- 26266521 TI - Impurities in Illicit Drug Preparations: Amphetamine and Methamphetamine. AB - In this review, attention is paid to chromatographic and mass spectral properties of already identified impurities found to be present in frequently abused drug preparations of illegal origin of amphetamine and methamphetamine. The most commonly employed methods of synthesis of drugs of this type are briefly described. Special emphasis is given to the Leuckart route, found to be the preferred method, in the illicit production of amphetamine. Furthermore, some isolation and preconcentration methods for the contaminants are discussed. The importance of identifying impurities present in amphetamine or methamphetamine cannot be overestimated. These impurities originate mostly from the improper purification in the end stage of the different syntheses used in the clandestine manufacture of the substances; it is possible to differentiate between the several kinds of illegal drug preparations, synthesized by various methods, by means of so-called "route specific" impurities. Finally, a survey is given of the impurities already known to be present in amphetamine and methamphetamine, together with their mass spectral and some chromatographic properties. PMID- 26266520 TI - Antitumoral activity of tyrosine kinase inhibitors in patients with non-small cell lung cancer harbouring rare epidermal growth factor receptor mutations. AB - INTRODUCTION: Mutations in the epidermal growth factor receptor (EGFR) have been reported as predictive markers of tumour response to tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). Although the "common" EGFR mutations have been associated with response to EGFR-TKIs, the correlation with response to treatment for many other rare mutations is still unclear. The aim of this study was to investigate the clinical significance of rare and complex mutations, and the efficacy of EGFR-TKIs in this selected group of patients. METHODS: Three hundred and thirty patients with stage IIIB/IV NSCLC (106 females aged 62.5 +/- 1.1 years; 224 males aged 68.0 +/- 0.6 years) were enrolled in the study. Formalin fixed paraffin embedded tissue samples were screened for mutations using a high resolution melting technique, followed by Sanger sequencing of exons 18-21 of the EGFR-gene. Mutation status was also tested using the Roche Cobas((r)) EGFR mutation test. RESULTS: EGFR mutations were detected in 31 tumours (9.4 %). Eleven cases carried novel mutations, six of these patients were treated with erlotinib or gefitinib. A response rate (RR) of 50.0 % was obtained in the group with rare EGFR mutations, the PFS was 3.0 months [standard deviation (STD) = 5.4 months]. The RR to EGFR-TKIs in patients with conventional EGFR mutations was 85 % with a median PFS of 10.5 months (STD = 3.6 months). CONCLUSION: We reported six patients with rare EGFR mutations of unknown clinical significance and their association with EGFR-TKIs. Report of cases harbouring rare mutations can support the decision making progress in this subset of patients. PMID- 26266519 TI - High frequency and poor prognosis of late childhood BCR-ABL-positive and MLL-AF4 positive ALL define the need for advanced molecular diagnostics and improved therapeutic strategies in pediatric B-ALL in Pakistan. AB - BACKGROUND: Fusion oncogenes (FOs) resulting from chromosomal abnormalities have an important role in leukemogenesis in pediatric B cell acute lymphoblastic leukemia (ALL). The most common FOs are BCR-ABL, MLL-AF4, ETV6-RUNX1, and TCF3 PBX1, all of which have important prognostic and drug selection implications. Moreover, frequencies of FOs have ethnic variations. We studied Pakistani frequencies of FOs, clinical pattern, and outcome in pediatric B-ALL. METHODS: FOs were studied in 188 patients at diagnosis using reverse transcriptase polymerase chain reaction (RT-PCR) and interphase fluorescent in situ hybridization (FISH). Data were analyzed using SPSS version 17 (SPSS Inc., Chicago, IL, USA). RESULTS: FOs were detected in 87.2 % of patients. Mean overall survival was 70.9 weeks, 3-year survival was 31.9 %, and 3-year relapse-free survival was 18.1 %. Four patients died of drug toxicities. ETV6-RUNX1 (19.14 %) had better survival (110.9 weeks; p = 0.03); TCF3-PBX1 (2.1 %) was associated with inferior outcome and higher central nervous system (CNS) relapse risk; MLL AF4 (18.1 %) was more common in the 8- to 15-year age group (24/34; p = 0.001) and was associated with organomegaly, low platelet count, and poor survival; and BCR-ABL (47.9 %) was associated with older age (7-15 years, 52/90), lower remission rates, shorter survival (43.73 +/- 4.24 weeks) and higher white blood cell count. Overall, MLL-AF4 and BCR-ABL were detected in 66 % of B-ALL, presented in later childhood, and were associated with poor prognosis and inferior survival. CONCLUSIONS: This study reports the highest ethnic frequency of BCR-ABL FO in pediatric ALL, and is consistent with previous reports from our region. Poor prognosis BCR-ABL and MLL-AF4 was detected in two-thirds of pediatric B-ALL and is likely to be the reason for the already reported poor survival of childhood ALL in South-East Asia. Furthermore, MLL-AF4, usually most common in infants, presented in later childhood in most of the ALL patients, which was one of the unique findings in our study. The results presented here highlight the need for mandatory inclusion of molecular testing for pediatric ALL patients in clinical decision making, together with the incorporation of tyrosine kinase inhibitors, as well as hematopoietic stem cell transplantation facilities, to improve treatment outcome for patients in developing countries. PMID- 26266522 TI - Morphine and Codeine in Biological Fluids: Approaches to Source Differentiation. AB - Heroin, morphine, and codeine are among the most abused opiate analgesics today. Analysis of individuals' urines for morphine and codeine is sued as an indication of prior ingestion of these dugs. Poppy seeds and products containing poppy seeds are found to have small amounts of morphine and codeine (usually less than 200 ug morphine/g seeds and much less codeine), which is enough to produce a positive urine test for opiates. This manuscript reviews current data on the analysis of various poppy seed products and urine specimens from individuals ingesting these products. A brief review of the metabolism and elimination of these drugs is presented, with general guidelines for differentiation of poppy seed use versus condone, morphine, or heroin abuse. PMID- 26266523 TI - Personal Identification of the Human Skull: Superimposition and Radiographic Techniques. AB - This paper constitutes a review of the literature and an evaluation of the anatomical relationships between skull and face, along with a discussion of the methodology involved in the various superimposition techniques used in forensic science. In addition, some unique anatomical traits and pathological findings are reviewed, with the hope that the information will find efficient use in the personal identification of unknown skulls. PMID- 26266524 TI - Pretreatment of Latent Prints for Laser Development. AB - The pretreatment procedures for laser detection of latent fingerprints is reviewed. The general features of laser detection and the operational aspects of the examination of physical evidence for laser fingerprint detection are enumerated in the initial sections. The literature review is divided into various pretreatment approaches. Cited studies prior to 1981 are primarily concerned with the demonstration of the viability of laser fingerprint detection, whereas work post-1981 addresses issues of compatibility with the traditional methods of fingerprint development, examination of difficult surfaces, and the routine implementation of laser detection by law enforcement agencies. Related topics of research, review articles, conference reports, case examinations, the research support climate, and future trends are also briefly addressed. PMID- 26266525 TI - The Use of Lectins in Forensic Science. AB - Lectins or receptor specific proteins have found a wide range of applications in biology and biochemistry as well as other life sciences. The original applications of these reagents in blood banking have been adapted to the unusual working conditions encountered by forensic scientists and lectins have been very useful in the analysis of blood and semen stains. First isolated as crude extracts from seeds, lectins are found in other plant parts as well and in a wide variety of invertebrate species. These reagents are now purified and characterized and have become versatile tools used to identify and group blood and other fluids both in clinical settings and in the often contaminated stains found at crime scenes. Human blood group antigens, especially the ABH antigens, have been extensively studied using these reagents, and the results have been extended to non-human blood group systems. Other applications include species determination and characterization. A review of the literature shows many papers delineating novel uses of lectins in the area of forensic serology. PMID- 26266526 TI - Structure and dynamics of a protein-surfactant assembly studied by ion-mobility mass spectrometry and molecular dynamics simulations. AB - The structure and dynamics of a protein-surfactant assembly studied by ion mobility mass spectrometry (IMS) and vacuum molecular dynamics (MD) simulations is reported. Direct evidence is provided for the ability of the surfactant dodecyl-beta-D-maltoside (DDM) to prevent charge-induced unfolding of the membrane protein (PagP) in the gas-phase. Restraints obtained by IMS are used to map the surfactant positions onto the protein surface. Surfactants occupying more exposed positions at the apexes of the beta-barrel structure are most in-line with the experimental observations. MD simulations provide additional evidence for this assembly organization through surfactant inversion and migration on the protein structure in the absence of solvent. Surfactant migration entails a net shift from apolar membrane spanning regions to more polar regions of the protein structure with the DDM molecule remaining attached to the protein via headgroup interactions. These data provide evidence for the role of protein-DDM headgroup interactions in stabilizing membrane protein structure from gas-phase unfolding. PMID- 26266527 TI - Building Evidence for Global Surgery One Experience at a Time. PMID- 26266528 TI - Controlling Short-Range Interactions by Tuning Surface Chemistry in HDPE/Graphene Nanoribbon Nanocomposites. AB - Unique dispersion states of nanoparticles in polymeric matrices have the potential to create composites with enhanced mechanical, thermal, and electrical properties. The present work aims to determine the state of dispersion from the melt-state rheological behavior of nanocomposites based on carbon nanotube and graphene nanoribbon (GNR) nanomaterials. GNRs were synthesized from nitrogen doped carbon nanotubes via a chemical route using potassium permanganate and some second acids. High-density polyethylene (HDPE)/GNR nanocomposite samples were then prepared through a solution mixing procedure. Different nanocomposite dispersion states were achieved using different GNR synthesis methods providing different surface chemistry, interparticle interactions, and internal compartments. Prolonged relaxation of flow induced molecular orientation was observed due to the presence of both carbon nanotubes and GNRs. Based on the results of this work, due to relatively weak interactions between the polymer and the nanofillers, it is expected that short-range interactions between nanofillers play the key role in the final dispersion state. PMID- 26266529 TI - Adequacy of nutritional intake among older men living in Sydney, Australia: findings from the Concord Health and Ageing in Men Project (CHAMP). AB - Previous research shows that older men tend to have lower nutritional intakes and higher risk of under-nutrition compared with younger men. The objectives of this study were to describe energy and nutrient intakes, assess nutritional risk and investigate factors associated with poor intake of energy and key nutrients in community-dwelling men aged >=75 years participating in the Concord Health and Ageing in Men Project - a longitudinal cohort study on older men in Sydney, Australia. A total of 794 men (mean age 81.4 years) had a detailed diet history interview, which was carried out by a dietitian. Dietary adequacy was assessed by comparing median intakes with nutrient reference values (NRV): estimated average requirement, adequate intake or upper level of intake. Attainment of NRV of total energy and key nutrients in older age (protein, Fe, Zn, riboflavin, Ca and vitamin D) was incorporated into a 'key nutrients' variable dichotomised as 'good' (>=5) or 'poor' (<=4). Using logistic regression modelling, we examined associations between key nutrients with factors known to affect food intake. Median energy intake was 8728 kJ (P5=5762 kJ, P95=12 303 kJ), and mean BMI was 27.7 (sd 4.0) kg/m2. Men met their NRV for most nutrients. However, only 1 % of men met their NRV for vitamin D, only 19 % for Ca, only 30 % for K and only 33 % for dietary fibre. Multivariate logistic regression analysis showed that only country of birth was significantly associated with poor nutritional intake. Dietary intakes were adequate for most nutrients; however, only half of the participants met the NRV of >=5 key nutrients. PMID- 26266530 TI - Tg in Adults as a Sensitive Biomarker of Iodine Status: A 5-Year Follow up Population Study in Different Levels of Iodine Intake Regions. AB - This study was to evaluate the usefulness of serum thymoglobulin (Tg) in adults to assess iodine status through a 5-year cohort study which was conducted in three regions with different levels of iodine intake: mild deficiency, more than adequate, and excess, from 1999 to 2004 in China. A total of 3099 subjects over 14 years old with normal serum levels of Tg in 1999 were eligible, of whom 2448 were followed in 2004. Serum levels of thyroid hormones and thyroid autoantibodies as well as urine iodine were measured, and B-mode ultrasonography of the thyroid was performed. A general linear model was performed to determine the determinant factors of serum Tg. Among subjects with mildly deficient iodine intake, those with more than adequate intake, and those with excessive intake, the baseline levels of serum Tg were substantially different (7.5MUg/L, 5.9MUg/L, and 6.8MUg/L respectively, P<0.01), which were associated with age, sex, the rate of positive TgAb, abnormal thyroid volume, abnormal TSH, and positive personal history of thyroid diseases. The data from 1856 subjects with normal range of thyroid parameters but no personal history of thyroid diseases were analyzed to clarify the effect of iodine intake on Tg. Among these three regions, the serum Tg levels were substantially different in both 1999 and 2004, with a similar pattern for increased Tg (DeltaTg) (3.1MUg/L, 2.5MUg/L and 3.5MUg/L respectively, P<0.01). The general linear model analysis revealed that age, Tg, and baseline TSH levels were the determinants of DeltaTg besides iodine intake. In conclusion, serum Tg in adults, resulting from a time-accumulative effect of iodine exposure, is a useful biomarker of regional iodine intake. PMID- 26266531 TI - Relationship between eating disturbance and dementia severity in patients with Alzheimer's disease. AB - BACKGROUND: Eating is one of the most important daily activities in managing patients with dementia. Although various eating disturbance occur as dementia progresses, to our knowledge, most of the studies focused on a part of eating disturbance such as swallowing and appetite. There have been few comprehensive studies including eating habits and food preference in patients with Alzheimer's disease (AD). The aims of this study were to investigate almost all eating disturbance and to examine the relationship of eating disturbance to dementia stage in AD. METHODS: A total of 220 patients with AD and 30 normal elderly (NE) subjects were recruited. Eating disturbance was assessed by a comprehensive questionnaire that had been previously validated. Potential relationships between the characteristics of eating disturbance and dementia stage as classified by the Clinical Dementia Rating (CDR) were assessed. RESULTS: Overall, 81.4% of patients with AD showed some eating and swallowing disturbance, whereas only 26.7% of the NE subjects had such a disturbance. Even in an early stage, patients with AD had many types of eating disturbance; "Appetite change" was shown in nearly half of the mild AD patients (49.5%). In the moderate stage, the scores of "change of eating habits and food preference" were highest, and in the severe stage "swallowing disturbance" became critical. CONCLUSION: In AD, the relationship of dementia stage to eating disturbance differs according to the type of eating disturbance. The relationships between various eating disturbance and the severity of dementia should be considered. PMID- 26266532 TI - Remediation of nitrobenzene contaminated soil by combining surfactant enhanced soil washing and effluent oxidation with persulfate. AB - The combination of surfactant enhanced soil washing and degradation of nitrobenzene (NB) in effluent with persulfate was investigated to remediate NB contaminated soil. Aqueous solution of sodium dodecylbenzenesulfonate (SDBS, 24.0 mmol L-1) was used at a given mass ratio of solution to soil (20:1) to extract NB contaminated soil (47.3 mg kg-1), resulting in NB desorption removal efficient of 76.8%. The washing effluent was treated in Fe2+/persulfate and Fe2+/H2O2 systems successively. The degradation removal of NB was 97.9%, being much higher than that of SDBS (51.6%) with addition of 40.0 mmol L-1 Fe2+ and 40.0 mmol L-1 persulfate after 15 min reaction. The preferential degradation was related to the lone pair electron of generated SO4*-, which preferably removes electrons from aromatic parts of NB over long alkyl chains of SDBS through hydrogen abstraction reactions. No preferential degradation was observed in *OH based oxidation because of its hydrogen abstraction or addition mechanism. The sustained SDBS could be reused for washing the contaminated soil. The combination of the effective surfactant-enhanced washing and the preferential degradation of NB with Fe2+/persulfate provide a useful option to remediate NB contaminated soil. PMID- 26266533 TI - Fat and carbohydrate intake over three generations modify growth, metabolism and cardiovascular phenotype in female mice in an age-related manner. AB - Environmental challenges such as a high fat diet during pregnancy can induce changes in offspring growth, metabolism and cardiovascular function. However, challenges that are sustained over several generations can induce progressive compensatory metabolic adjustments in young adults. It is not known if such effects persist during ageing. We investigated whether diets with different fat and carbohydrate contents over three generations modifies markers of ageing. Female C57BL/6 F0 mice were fed diets containing 5% or 21% fat (w/w) throughout pregnancy and lactation. Female offspring were fed the same diet as their dams until the F3 generation. In each generation, body weight, 24-hour food intake were recorded weekly, and plasma metabolites were measured by colorimetric assays, blood pressure by tail cuff plethysmography and vasoconstriction by myography on postnatal day 90 or 456. There was little effect of diet or generation on phenotypic markers in day 90 adults. There was a significant increase in whole body, liver and heart weight with ageing (d456) in the F3 21% fat group compared to the F1 and F3 5% groups. Fasting plasma glucose concentration was significantly increased with ageing in the 5% group in the F3 generation and in the 21% group in both generations. There was a significant effect of diet and generation on ex-vivo vasoconstriction in ageing females. Differences in dietary fat may induce metabolic compensation in young adults that persist over three generations. However, such compensatory effects decline during ageing. PMID- 26266534 TI - Correction: Analysis of Deregulated microRNAs and Their Target Genes in Gastric Cancer. PMID- 26266535 TI - Global Gene Expression Profiling through the Complete Life Cycle of Trypanosoma vivax. AB - The parasitic flagellate Trypanosoma vivax is a cause of animal trypanosomiasis across Africa and South America. The parasite has a digenetic life cycle, passing between mammalian hosts and insect vectors, and a series of developmental forms adapted to each life cycle stage. Each point in the life cycle presents radically different challenges to parasite metabolism and physiology and distinct host interactions requiring remodeling of the parasite cell surface. Transcriptomic and proteomic studies of the related parasites T. brucei and T. congolense have shown how gene expression is regulated during their development. New methods for in vitro culture of the T. vivax insect stages have allowed us to describe global gene expression throughout the complete T. vivax life cycle for the first time. We combined transcriptomic and proteomic analysis of each life stage using RNA seq and mass spectrometry respectively, to identify genes with patterns of preferential transcription or expression. While T. vivax conforms to a pattern of highly conserved gene expression found in other African trypanosomes, (e.g. developmental regulation of energy metabolism, restricted expression of a dominant variant antigen, and expression of 'Fam50' proteins in the insect mouthparts), we identified significant differences in gene expression affecting metabolism in the fly and a suite of T. vivax-specific genes with predicted cell surface expression that are preferentially expressed in the mammal ('Fam29, 30, 42') or the vector ('Fam34, 35, 43'). T. vivax differs significantly from other African trypanosomes in the developmentally-regulated proteins likely to be expressed on its cell surface and thus, in the structure of the host-parasite interface. These unique features may yet explain the species differences in life cycle and could, in the form of bloodstream-stage proteins that do not undergo antigenic variation, provide targets for therapy. PMID- 26266536 TI - Population genetics and new insight into range of CAG repeats of spinocerebellar ataxia type 3 in the Han Chinese population. AB - Spinocerebellar ataxia type 3 (SCA3), also called Machado-Joseph disease (MJD), is one of the most common SCAs worldwide and caused by a CAG repeat expansion located in ATXN3 gene. Based on the CAG repeat numbers, alleles of ATXN3 can be divided into normal alleles (ANs), intermediate alleles (AIs) and expanded alleles (AEs). It was controversial whether the frequency of large normal alleles (large ANs) is related to the prevalence of SCA3 or not. And there were huge chaos in the comprehension of the specific numbers of the range of CAG repeats which is fundamental for genetic analysis of SCA3. To illustrate these issues, we made a novel CAG repeat ladder to detect CAG repeats of ATXN3 in 1003 unrelated Chinese normal individuals and studied haplotypes defined by three single nucleotide polymorphisms (SNPs) closed to ATXN3. We found that the number of CAG repeats ranged from 13 to 49, among them, 14 was the most common number. Positive skew, the highest frequency of large ANs and 4 AIs which had never been reported before were found. Also, AEs and large ANs shared the same haplotypes defined by the SNPs. Based on these data and other related studies, we presumed that de novo mutations of ATXN3 emerging from large ANs are at least one survival mechanisms of mutational ATXN3 and we can redefine the range of CAG repeats as: ANs<=44, 45 <=AIs <=49 and AEs>=50. PMID- 26266537 TI - Spatiotemporal Spike Coding of Behavioral Adaptation in the Dorsal Anterior Cingulate Cortex. AB - The frontal cortex controls behavioral adaptation in environments governed by complex rules. Many studies have established the relevance of firing rate modulation after informative events signaling whether and how to update the behavioral policy. However, whether the spatiotemporal features of these neuronal activities contribute to encoding imminent behavioral updates remains unclear. We investigated this issue in the dorsal anterior cingulate cortex (dACC) of monkeys while they adapted their behavior based on their memory of feedback from past choices. We analyzed spike trains of both single units and pairs of simultaneously recorded neurons using an algorithm that emulates different biologically plausible decoding circuits. This method permits the assessment of the performance of both spike-count and spike-timing sensitive decoders. In response to the feedback, single neurons emitted stereotypical spike trains whose temporal structure identified informative events with higher accuracy than mere spike count. The optimal decoding time scale was in the range of 70-200 ms, which is significantly shorter than the memory time scale required by the behavioral task. Importantly, the temporal spiking patterns of single units were predictive of the monkeys' behavioral response time. Furthermore, some features of these spiking patterns often varied between jointly recorded neurons. All together, our results suggest that dACC drives behavioral adaptation through complex spatiotemporal spike coding. They also indicate that downstream networks, which decode dACC feedback signals, are unlikely to act as mere neural integrators. PMID- 26266538 TI - c-Myc Alters Substrate Utilization and O-GlcNAc Protein Posttranslational Modifications without Altering Cardiac Function during Early Aortic Constriction. AB - Hypertrophic stimuli cause transcription of the proto-oncogene c-Myc (Myc). Prior work showed that myocardial knockout of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we assessed the interplay between Myc, substrate oxidation and cardiac function during early pressure overload hypertrophy. Mice with cardiac specific, inducible Myc knockout (MycKO-TAC) and non-transgenic littermates (Cont-TAC) were subjected to transverse aortic constriction (TAC; n = 7/group). Additional groups underwent sham surgery (Cont-Sham and MycKO-Sham, n = 5 per group). After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. In sham hearts, Myc knockout did not affect cardiac function or substrate preferences for the citric acid cycle. However, Myc knockout altered fractional contributions during TAC. The unlabeled fractional contribution increased in MycKO-TAC versus Cont-TAC, whereas ketone and free fatty acid fractional contributions decreased. Additionally, protein posttranslational modifications by O-GlcNAc were significantly greater in Cont-TAC versus both Cont-Sham and MycKO-TAC. In conclusion, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy, which may regulate Myc-induced metabolic changes. PMID- 26266539 TI - Molecular Evolution of PvMSP3alpha Block II in Plasmodium vivax from Diverse Geographic Origins. AB - Block II of Plasmodium vivax merozoite surface protein 3alpha (PvMSP3alpha) is conserved and has been proposed as a potential candidate for a malaria vaccine. The present study aimed to compare sequence diversity in PvMSP3a block II at a local microgeographic scale in a village as well as from larger geographic regions (countries and worldwide). Blood samples were collected from asymptomatic carriers of P. vivax in a village at the western border of Thailand and PvMSP3alpha was amplified and sequenced. For population genetic analysis, 237 PvMSP3alpha block II sequences from eleven P. vivax endemic countries were analyzed. PvMSP3alpha sequences from 20 village-level samples revealed two length variant types with one type containing a large deletion in block I. In contrast, block II was relatively conserved; especially, some non-synonymous mutations were extensively shared among 11 parasite populations. However, the majority of the low-frequency synonymous variations were population specific. The conserved pattern of nucleotide diversity in block II sequences was probably due to functional/structural constraints, which were further supported by the tests of neutrality. Notably, a small region in block II that encodes a predicted B cell epitope was highly polymorphic and showed signs of balancing selection, signifying that this region might be influenced by the immune selection and may serve as a starting point for designing multi-antigen/stage epitope based vaccines against this parasite. PMID- 26266540 TI - Ethanol upregulates NMDA receptor subunit gene expression in human embryonic stem cell-derived cortical neurons. AB - Chronic alcohol consumption may result in sustained gene expression alterations in the brain, leading to alcohol abuse or dependence. Because of ethical concerns of using live human brain cells in research, this hypothesis cannot be tested directly in live human brains. In the present study, we used human embryonic stem cell (hESC)-derived cortical neurons as in vitro cellular models to investigate alcohol-induced expression changes of genes involved in alcohol metabolism (ALDH2), anti-apoptosis (BCL2 and CCND2), neurotransmission (NMDA receptor subunit genes: GRIN1, GRIN2A, GRIN2B, and GRIN2D), calcium channel activity (ITPR2), or transcriptional repression (JARID2). hESCs were differentiated into cortical neurons, which were characterized by immunostaining using antibodies against cortical neuron-specific biomarkers. Ethanol-induced gene expression changes were determined by reverse-transcription quantitative polymerase chain reaction (RT-qPCR). After a 7-day ethanol (50 mM) exposure followed by a 24-hour ethanol withdrawal treatment, five of the above nine genes (including all four NMDA receptor subunit genes) were highly upregulated (GRIN1: 1.93-fold, P = 0.003; GRIN2A: 1.40-fold, P = 0.003; GRIN2B: 1.75-fold, P = 0.002; GRIN2D: 1.86 fold, P = 0.048; BCL2: 1.34-fold, P = 0.031), and the results of GRIN1, GRIN2A, and GRIN2B survived multiple comparison correction. Our findings suggest that alcohol responsive genes, particularly NMDA receptor genes, play an important role in regulating neuronal function and mediating chronic alcohol consumption induced neuroadaptations. PMID- 26266542 TI - Fine-Scale Cartography of Human Impacts along French Mediterranean Coasts: A Relevant Map for the Management of Marine Ecosystems. AB - Ecosystem services provided by oceans and seas support most human needs but are threatened by human activities. Despite existing maps illustrating human impacts on marine ecosystems, information remains either large-scale but rough and insufficient for stakeholders (1 km2 grid, lack of data along the coast) or fine scale but fragmentary and heterogeneous in methodology. The objectives of this study are to map and quantify the main pressures exerted on near-coast marine ecosystems, at a large spatial scale though in fine and relevant resolution for managers (one pixel = 20 x 20 m). It focuses on the French Mediterranean coast (1,700 km of coastline including Corsica) at a depth of 0 to 80 m. After completing and homogenizing data presently available under GIS on the bathymetry and anthropogenic pressures but also on the seabed nature and ecosystem vulnerability, we provide a fine modeling of the extent and impacts of 10 anthropogenic pressures on marine habitats. The considered pressures are man-made coastline, boat anchoring, aquaculture, urban effluents, industrial effluents, urbanization, agriculture, coastline erosion, coastal population and fishing. A 1:10 000 continuous habitat map is provided considering 11 habitat classes. The marine bottom is mostly covered by three habitats: infralittoral soft bottom, Posidonia oceanica meadows and circalittoral soft bottom. Around two thirds of the bottoms are found within medium and medium high cumulative impact categories. Seagrass meadows are the most impacted habitats. The most important pressures (in area and intensity) are urbanization, coastal population, coastal erosion and man made coastline. We also identified areas in need of a special management interest. This work should contribute to prioritize environmental needs, as well as enhance the development of indicators for the assessment of the ecological status of coastal systems. It could also help better apply and coordinate management measures at a relevant scale for biodiversity conservation. PMID- 26266541 TI - Differential Effects of Sodium Butyrate and Lithium Chloride on Rhesus Monkey Trophoblast Differentiation. AB - Trophoblast differentiation during early placental development is critical for successful pregnancy and aberrant differentiation causes preeclampsia and early pregnancy loss. During the first trimester, cytotrophoblasts are exposed to low oxygen tension (equivalent to~2%-3% O2) and differentiation proceeds along an extravillous pathway (giving rise to invasive extravillous cytotrophoblasts) and a villous pathway (giving rise to multinucleated syncytiotrophoblast). Interstitial extravillous cytotrophoblasts invade the decidua, while endovascular extravillous cytotrophoblasts are involved in re-modelling uterine spiral arteries. We tested the idea that sodium butyrate (an epigenetic modulator) induces trophoblast differentiation in early gestation rhesus monkey trophoblasts through activation of the Wnt/beta-catenin pathway. The results show that syncytiotrophoblast formation was increased by butyrate, accompanied by nuclear accumulation of beta-catenin, and increased expression of EnvV2 and galectin-1 (two factors thought to be involved in trophoblast fusion). Surprisingly, the expression of GCM1 and syncytin-2 was not affected by sodium butyrate. When trophoblasts were incubated with lithium chloride, a GSK3 inhibitor that mimics Wnt activation, nuclear accumulation of beta-catenin also occurred but differentiation into syncytiotrophoblast was not observed. Instead the cells differentiated to mononucleated spindle-shaped cells and showed molecular and behavioral characteristics of endovascular trophoblasts. Another highly specific inhibitor of GSK3, CHIR99021, failed to induce endovascular trophoblast characteristics. These observations suggest that activation of the Wnt/beta catenin pathway correlates with both trophoblast differentiation pathways, but that additional factors determine specific cell fate decisions. Other experiments suggested that the differential effects of sodium butyrate and lithium chloride might be explained by their effects on TNFalpha production. The results provide valuable tools to manipulate trophoblast differentiation in vitro and to better understand the differentiation pathways that occur during early gestation. PMID- 26266543 TI - Behavior and Body Patterns of the Larger Pacific Striped Octopus. AB - Over thirty years ago anecdotal accounts of the undescribed Larger Pacific Striped Octopus suggested behaviors previously unknown for octopuses. Beak-to beak mating, dens shared by mating pairs, inking during mating and extended spawning were mentioned in publications, and enticed generations of cephalopod biologists. In 2012-2014 we were able to obtain several live specimens of this species, which remains without a formal description. All of the unique behaviors listed above were observed for animals in aquaria and are discussed here. We describe the behavior, body color patterns, and postures of 24 adults maintained in captivity. Chromatophore patterns of hatchlings are also shown. PMID- 26266545 TI - iMAR: An Interactive Web-Based Application for Mapping Herbicide Resistant Weeds. AB - Herbicides are the major weed control tool in most cropping systems worldwide. However, the high reliance on herbicides has led to environmental issues as well as to the evolution of herbicide-resistant biotypes. Resistance is a major concern in modern agriculture and early detection of resistant biotypes is therefore crucial for its management and prevention. In this context, a timely update of resistance biotypes distribution is fundamental to devise and implement efficient resistance management strategies. Here we present an innovative web based application called iMAR (interactive MApping of Resistance) for the mapping of herbicide resistant biotypes. It is based on open source software tools and translates into maps the data reported in the GIRE (Italian herbicide resistance working group) database of herbicide resistance at national level. iMAR allows an automatic, easy and cost-effective updating of the maps a nd provides two different systems, "static" and "dynamic". In the first one, the user choices are guided by a hierarchical tree menu, whereas the latter is more flexible and includes a multiple choice criteria (type of resistance, weed species, region, cropping systems) that permits customized maps to be created. The generated information can be useful to various stakeholders who are involved in weed resistance management: farmers, advisors, national and local decision makers as well as the agrochemical industry. iMAR is freely available, and the system has the potential to handle large datasets and to be used for other purposes with geographical implications, such as the mapping of invasive plants or pests. PMID- 26266544 TI - Differentiate or Die: 3-Bromopyruvate and Pluripotency in Mouse Embryonic Stem Cells. AB - BACKGROUND: Pluripotent embryonic stem cells grown under standard conditions (ESC) have a markedly glycolytic profile, which is shared with many different types of cancer cells. Thus, some therapeutic strategies suggest that pharmacologically shifting cancer cells towards an oxidative phenotype, using glycolysis inhibitors, may reduce cancer aggressiveness. Given the metabolic parallels between cancer and stemness would chemotherapeutical agents have an effect on pluripotency, and could a strategy involving these agents be envisioned to modulate stem cell fate in an accessible manner? In this manuscript we attempted to determine the effects of 3-bromopyruvate (3BrP) in pluripotency. Although it has other intracellular targets, this compound is a potent inhibitor of glycolysis enzymes thought to be important to maintain a glycolytic profile. The goal was also to determine if we could contribute towards a pharmacologically accessible metabolic strategy to influence cell differentiation. METHODOLOGY/PRINCIPAL FINDINGS: Mouse embryonic stem cells (mESC) grown under standard pluripotency conditions (in the presence of Leukemia Inducing Factor- LIF) were treated with 3BrP. As a positive control for differentiation other mESCs were grown without LIF. Overall our results demonstrate that 3BrP negatively affects pluripotency, forcing cells to become less glycolytic and with more active mitochondria. These changes in metabolism are correlated with increased differentiation, even under pluripotency conditions (i.e. in the presence of LIF). However, 3BrP also significantly impaired cell function, and may have other roles besides affecting the metabolic profile of mESCs. CONCLUSIONS/FINDINGS: Treatment of mESCs with 3BrP triggered a metabolic switch and loss of pluripotency, even in the presence of LIF. Interestingly, the positive control for differentiation allowed for a distinction between 3BrP effects and changes associated with spontaneous differentiation/loss of pluripotency in the absence of LIF. Additionally, there was a slight differentiation bias towards mesoderm in the presence of 3BrP. However, the side effects on cellular function suggest that the use of this drug is probably not adequate to efficiently push cells towards specific differentiation fates. PMID- 26266546 TI - Antihypertensive Effect of a Combination of Uracil and Glycerol Derived from Lactobacillus plantarum Strain TWK10-Fermented Soy Milk. AB - We previously demonstrated that angiotensin-converting enzyme (ACE) could be inhibited by soy milk that had been fermented with the Lactobacillus plantarum strain TWK10, suggesting great potential for the development of antihypertensive products. In this work, the bioactive ACE inhibitors in TWK10-fermented soy milk water extracts were isolated, and a combination of uracil and glycerol (CUG) was identified as one of the ACE inhibitors. We then examined the physiological effects of CUG treatment in short-term and long-term studies using spontaneously hypertensive rats (SHRs) as an experimental model. The results revealed that the fermented soy milk extracts and CUG decreased blood pressure by 11.97 +/- 3.71 to 19.54 +/- 9.54 mmHg, 8 h after oral administration, and exhibited antihypertensive effects in SHRs in a long-term study. In addition, CUG was shown to decrease blood pressure by suppressing either the renin activity or the ACE activity and, thus, decreasing the downstream vasoconstricting peptide angiotensin II and the hormone aldosterone. CUG also promoted nitric oxide production, resulting in vasodilation and further improvement to hypertension. This important finding suggests that TWK10-fermented soy milk and its functional ingredients, uracil and glycerol, exhibit antihypertensive effects via multiple pathways and provide a healthier and more natural antihypertensive functional food. PMID- 26266547 TI - Stepwise Expansion of Pd Chains from Binuclear Palladium(I) Complexes Supported by Tetraphosphine Ligands. AB - Reaction of [Pd2(XylNC)6]X2 (X = PF6, BF4) with a linear tetraphosphine, meso bis[(diphenylphosphinomethyl)phenylphosphino]methane (dpmppm), afforded binuclear Pd(I) complexes, [Pd2(MU-dpmppm)2]X2 ([2]X2), through an asymmetric dipalladium complex, [Pd2(MU-dpmppm)(XylNC)3](2+) ([1](2+)). Complex [2](2+) readily reacted with [Pd(0)(dba)2] (2 equiv) and an excess of isocyanide, RNC (R = 2,6-xylyl (Xyl), tert-butyl ((t)Bu)), to generate an equilibrium mixture of [Pd4(MU dpmppm)2(RNC)2](2+) ([3'](2+)) + RNC ? [Pd4(MU-dpmppm)2(RNC)3](2+) ([3](2+)), from which [Pd4(MU-dpmppm)2(XylNC)3](2+) ([3a](2+)) and [Pd4(MU dpmppm)2((t)BuNC)2](2+) ([3b'](2+)) were isolated. Variable-temperature UV-vis and (31)P{(1)H} and (1)H NMR spectroscopic studies on the equilibrium mixtures demonstrated that the tetrapalladium complexes are quite fluxional in the solution state: the symmetric Pd4 complex [3b'](2+) predominantly existed at higher temperatures (>0 degrees C), and the equilibrium shifted to the asymmetric Pd4 complex [3b](2+) at a low temperature (~-30 degrees C). The binding constants were determined by UV-vis titration at 20 degrees C and revealed that XylNC is of higher affinity to the Pd4 core than (t)BuNC. In addition, both isocyanides exhibited higher affinity to the electron deficient [Pd4(MU-dpmppmF2)2(RNC)2](2+) ([3F'](2+)) than to [Pd4(MU-dpmppm)2(RNC)2](2+) ([3'](2+)) (dpmppmF2 = meso-bis[{di(3,5 difluorophenyl)phosphinomethyl}phenylphosphino]methane). When [2]X2 was treated with [Pd(0)(dba)2] (2 equiv) in the absence of RNC in acetonitrile, linearly ordered octapalladium chains, [Pd8(MU-dpmppm)4(CH3CN)2]X4 ([4]X4: X = PF6, BF4), were generated through a coupling of two {Pd4(MU-dpmppm)2}(2+) fragments. Complex [2](2+) was also proven to be a good precursor for Pd2M2 mixed-metal complexes, yielding [Pd2Cl(Cp*MCl) (Cp*MCl2)(MU-dpmppm)2](2+) (M = Rh ([5](2+)), Ir ([6](2+)), and [Au2Pd2Cl2(dpmppm-H)2](2+) ([7](2+)) by treatment with [Cp*MCl2]2 and [AuCl(PPh3)], respectively. Complex [7](2+) contains an unprecedented PC(sp(3))P pincer ligand with a PCPCPCP backbone, dpmppm-H of deprotonated dpmppm. The present results demonstrated that the binuclear Pd(I) complex [2](2+) was a quite useful starting material to extend the palladium chains and to construct Pd-involved heteromultinuclear systems. PMID- 26266548 TI - Plasmonic mass and Johnson-Nyquist noise. AB - The fluctuation-dissipation theorem relates the thermal noise spectrum of a conductor to its linear response properties, with the ohmic resistance arising from the electron scattering being the most notable linear response property. But the linear response also includes the collective inertial acceleration of electrons, which should in principle influence the thermal noise spectrum as well. In practice, this effect would be largely masked by the Planck quantization for traditional conductors with short electron scattering times. But recent advances in nanotechnology have enabled the fabrication of conductors with greatly increased electron scattering times, with which the collective inertial effect can critically affect the thermal noise spectrum. In this paper we highlight this collective inertial effect-that is, the plasmonic effect-on the thermal noise spectrum under the framework of semiclassical electron dynamics, from both fundamental microscopic and practical modeling points of view. In graphene, where non-zero collective inertia arises from zero single-electron effective mass and where both electron and hole bands exist together, the thermal noise spectrum shows rich temperature and frequency dependencies, unseen in traditional conductors. PMID- 26266549 TI - A Conformational Shift in the Dissociated Cholera Toxin A1 Subunit Prevents Reassembly of the Cholera Holotoxin. AB - Cholera toxin (CT) consists of a catalytic A1 subunit, an A2 linker, and a homopentameric cell-binding B subunit. The intact holotoxin moves by vesicle carriers from the cell surface to the endoplasmic reticulum (ER) where CTA1 is released from the rest of the toxin. The dissociated CTA1 subunit then shifts to an unfolded conformation, which triggers its export to the cytosol by a process involving the quality control system of ER-associated degradation (ERAD). We hypothesized that the unfolding of dissociated CTA1 would prevent its non productive reassociation with CTA2/CTB5. To test this prediction, we monitored the real-time reassociation of CTA1 with CTA2/CTB5 by surface plasmon resonance. Folded but not disordered CTA1 could interact with CTA2/CTB5 to form a stable, functional holotoxin. Our data, thus, identified another role for the intrinsic instability of the isolated CTA1 polypeptide in host-toxin interactions: in addition to activating the ERAD translocation mechanism, the spontaneous unfolding of free CTA1 at 37 degrees C prevents the non-productive reassembly of a CT holotoxin in the ER. PMID- 26266550 TI - The evolution of carrying capacity in constrained and expanding tumour cell populations. AB - Cancer cells are known to modify their micro-environment such that it can sustain a larger population, or, in ecological terms, they construct a niche which increases the carrying capacity of the population. It has however been argued that niche construction, which benefits all cells in the tumour, would be selected against since cheaters could reap the benefits without paying the cost. We have investigated the impact of niche specificity on tumour evolution using an individual based model of breast tumour growth, in which the carrying capacity of each cell consists of two components: an intrinsic, subclone-specific part and a contribution from all neighbouring cells. Analysis of the model shows that the ability of a mutant to invade a resident population depends strongly on the specificity. When specificity is low selection is mostly on growth rate, while high specificity shifts selection towards increased carrying capacity. Further, we show that the long-term evolution of the system can be predicted using adaptive dynamics. By comparing the results from a spatially structured versus well-mixed population we show that spatial structure restores selection for carrying capacity even at zero specificity, which poses a solution to the niche construction dilemma. Lastly, we show that an expanding population exhibits spatially variable selection pressure, where cells at the leading edge exhibit higher growth rate and lower carrying capacity than those at the centre of the tumour. PMID- 26266551 TI - Activity in mice of recombinant BCG-EgG1Y162 vaccine for Echinococcus granulosus infection. AB - Cystic hydatid disease is a zoonotic parasitic disease caused by Echinococcus granulosus which is distributed worldwide. The disease is difficult to treat with surgery removal is the only cure treatment. In the high endemic areas, vaccination of humans is believed a way to protect communities from the disease. In this study we vaccinated BALB/c mice with rBCG-EgG1Y162, and then detected the level of IgG and IgE specifically against the recombinant protein by ELISA, rBCG EgG1Y162 induced strong and specific cellular and humoral immune responses. In vitro study showed that rBCG-EgG1Y162 vaccine not only promote splenocytes proliferation but also active T cell. In addition, the rBCG-EgG1Y162 induced a protection in the mice against secondary infection of Echinococcus granulosus. PMID- 26266553 TI - Outcomes of Surgical Treatment of Posterolateral Instability of the Knee. AB - The purpose of this review is to assess the outcomes of surgical treatment of posterolateral instability of the knee in an evidence-based manner. The majority of the existing outcomes literature on posterolateral instability consists of small, level IV case series and level III retrospective studies. Outcomes of surgical treatment of posterolateral instability of the knee are difficult to compare because of the heterogeneous presentation of posterolateral corner (PLC) injuries, the variability of their associated injuries, and their relative rarity. As such, three common types of surgical intervention for posterolateral instability are explored separately in this article, including acute repair, acute reconstruction, and chronic reconstruction. In general, the current literature supports early anatomic repair of all soft tissues and concomitant PLC reconstruction; however, because of the variability of posterolateral injury, surgical treatment options should be tailored to the patient, depending on the severity and chronicity of the posterolateral instability, as well as the associated injuries present. PMID- 26266552 TI - When and How Is Patella Tracking Best Assessed in Total Knee Arthroplasty Surgery? AB - Much emphasis has been placed on the role of patella resurfacing in total knee arthroplasty (TKA), yet the impact of soft tissue balancing has frequently been understated. The authors used a novel system to precisely assess patellofemoral joint (PFJ) tracking intraoperatively, to determine the impact of both retinacular reconstruction and tourniquet use on PFJ kinematics. PFJ kinematics assessed intraoperatively for 20 consecutive TKA patients. Measurements were recorded using both the "no thumb technique" and following reconstruction of the retinaculum with two positional sutures. The tourniquet was deflated and both measurements were repeated. Tourniquet inflation was not found to have a significant impact on the patella tracking (mean translation 0.9 mm, p = 0.15). Patella retinacular reconstruction generated a significant medialization of the patella by a mean of 5.5 mm (p < 0.0001) when compared with the traditional retinacular open "no thumb technique." The use of a tourniquet has been shown to have no effect on patella tracking. Reconstruction of the patella retinaculum markedly improves patella tracking, generating a mean medialization of 15%. The authors advocate the routine use of two positional sutures to restore the patella retinaculum, before trialing the patella component, as a reproducible means of assessing the PFJ kinematics. PMID- 26266554 TI - Competition Between H2SO4(-)(CH3)3N and H2SO4-H2O Interactions: Theoretical Studies on the Clusters [(CH3)3N].(H2SO4).(H2O)(3-7). AB - The role of the nucleation of sulfuric acid with amines in aerosol formation and its implications for environment is one of the fundamental unsettled questions in atmospheric chemistry. We have investigated the cluster of [(CH3)3N].(H2SO4).(H2O)n (n = 3-7) by molecular dynamics to obtain configurational sampling combination with CAM-B3LYP/6-311G(d,p) level to locate the global and many local minima for each cluster size. According to the binding energies at the method of MP2/6-311++G(d,p), the total binding energies decrease with the increasing of the water molecules. For each global minimum, the average binding energies decrease from n = 3 to 4, then increase slowly. The protons of H2SO4 are preferred to transfer to the (CH3)3N to form ion-pair HSO4(-) and (CH3)3NH(+), and the (CH3)3NH(+) ions are coordinated at the first hydrated shell of HSO4(-) when n is between 3 and 5 and coordinated at the second or third hydrated shell when n is larger than 5. PMID- 26266555 TI - Monitoring Assembly of Virus Capsids with Nanofluidic Devices. AB - Virus assembly is a coordinated process in which typically hundreds of subunits react to form complex, symmetric particles. We use resistive-pulse sensing to characterize the assembly of hepatitis B virus core protein dimers into T = 3 and T = 4 icosahedral capsids. This technique counts and sizes intermediates and capsids in real time, with single-particle sensitivity, and at biologically relevant concentrations. Other methods are not able to produce comparable real time, single-particle observations of assembly reactions below, near, and above the pseudocritical dimer concentration, at which the dimer and capsid concentrations are approximately equal. Assembly reactions across a range of dimer concentrations reveal three distinct patterns. At dimer concentrations as low as 50 nM, well below the pseudocritical dimer concentration of 0.5 MUM, we observe a switch in the ratio of T = 3 to T = 4 capsids, which increases with decreasing dimer concentration. Far above the pseudocritical dimer concentration, kinetically trapped, incomplete T = 4 particles assemble rapidly, then slowly anneal into T = 4 capsids. At all dimer concentrations tested, T = 3 capsids form more rapidly than T = 4 capsids, suggesting distinct pathways for the two forms. PMID- 26266557 TI - Relieving the pressure at LNS 2015. PMID- 26266556 TI - The Role of Short-Chain Fatty Acids, Produced by Anaerobic Bacteria, in the Cystic Fibrosis Airway. AB - RATIONALE: Anaerobic bacteria are present in large numbers in the airways of people with cystic fibrosis (PWCF). In the gut, anaerobes produce short-chain fatty acids (SCFAs) that modulate immune and inflammatory processes. OBJECTIVES: To investigate the capacity of anaerobes to contribute to cystic fibrosis (CF) airway pathogenesis via SCFAs. METHODS: Samples of 109 PWCF were processed using anaerobic microbiological culture with bacteria present identified by 16S RNA sequencing. SCFA levels in anaerobic supernatants and bronchoalveolar lavage (BAL) were determined by gas chromatography. The mRNA and/or protein expression of two SCFA receptors, GPR41 and GPR43, in CF and non-CF bronchial brushings and 16HBE14o(-) and CFBE41o(-) cells were evaluated using reverse transcription polymerase chain reaction, Western blot analysis, laser scanning cytometry, and confocal microscopy. SCFA-induced IL-8 secretion was monitored by ELISA. MEASUREMENTS AND MAIN RESULTS: Fifty-seven (52.3%) of 109 PWCF were anaerobe positive. Prevalence increased with age, from 33.3% to 57.7% in PWCF younger (n = 24) and older (n = 85) than 6 years of age. All evaluated anaerobes produced millimolar concentrations of SCFAs, including acetic, propionic, and butyric acids. SCFA levels were higher in BAL samples of adults than in those of children. GPR41 levels were elevated in CFBE41o(-) versus 16HBE14o(-) cells; CF versus non-CF bronchial brushings; and 16HBE14o(-) cells after treatment with cystic fibrosis transmembrane conductance regulator inhibitor CFTR(inh)-172, CF BAL, or inducers of endoplasmic reticulum stress. SCFAs induced a dose-dependent and pertussis toxin-sensitive IL-8 response in bronchial epithelial cells, with a higher production of IL-8 in CFBE41o(-) than in 16HBE14o(-) cells. CONCLUSIONS: This study illustrates that SCFAs contribute to excessive production of IL-8 in CF airways colonized with anaerobes via up-regulated GPR41. PMID- 26266558 TI - Managing the problem of excess exudate. AB - Wound healing is a normal response to injury and is initiated after the integrity of the skin has been interrupted. The management of exudate in practice can be challenging, as there are clinical situations where the patient's wound may produce copious amounts of exudate. It is therefore important that excess wound exudate is accurately assessed and diagnosed and subsequently managed effectively to relieve the significant burden it places on those who suffer with the problem. This article will look at the effect of Exufiber((r)) in the management of three wounds with different aetiologies. PMID- 26266559 TI - Is there a difference between debridement and desloughing? PMID- 26266560 TI - An observational evaluation of a new foam adhesive dressing. AB - Following the work of Winter demonstrating the benefits of moist wound healing, there has been a constant stream of wound care products launched into the market to support this concept. This article will describe the findings of an observational evaluation to observe, document and analyse the clinical effectiveness of a new foam adhesive dressing, UrgoTul(r) Absorb Border (Urgo Medical). The main objective of the evaluation was to define the parameters to allow data capture that would demonstrate the clinical effectiveness of the dressing. Parameters studied and analysed included atraumatic pain-free dressing changes; ease of dressing application; comfort and conformability; exudate management; ability of the dressing to stay in place; and peri-wound skin management. A total of 25 patients with wounds suitable to be dressed using the evaluation product were recruited following a full documented wound assessment by the tissue viability nurse. Participants were selected across the organisation from acute hospital wards and outpatient departments, care homes, wound care clinics and the participants' own homes. Digital photography was used to demonstrate improvement or deterioration of the wound bed and surrounding skin, and images were assessed by non-participating clinicians to confirm documented observations made within the evaluation. The dressing was found to be clinically effective in both chronic and acute wound types, and had an excellent level of participant acceptance. PMID- 26266562 TI - A 7-day NHS service for all? PMID- 26266561 TI - A clinical in-market evaluation of an alginate fibre dressing. AB - Practice nurses working in GP surgeries are responsible for caring for patients with both acute and chronic wounds. The management of wounds is challenging and it is important to achieve and maintain an optimum healing environment. As practice nurses play an integral part in managing both acute and chronic wounds within a community setting, it is essential that they can make informed decisions as to which products to use. A clinical in-market evaluation of 23 patients was carried out to assess the performance of ActivHeal Aquafiber(r) in clinical practice. Overall, the dressing performed well in respect of fluid handling and durability. The dressing addressed patient needs in terms of easy application and removal, prevention of leakage and wound progression. PMID- 26266563 TI - MRSA decontamination using octenidine-based products. AB - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infections are an increasing problem worldwide with a high risk of severe illness and mortality in hospitalised patients. Patients with chronic wounds are at particular risk of developing MRSA infections. As octenidine-based products have shown promising success in decontamination in the past, the aim of the present study was to determine its efficacy, safety, and tolerability in decontaminating hospitalised MRSA-positive patients. METHODS: From 1 April 2011 until 9 November 2012, 36 patients were screened MRSA-positive at the Republican Vilnius University Hospital, Vilnius, Lithuania. At least three swab tests were performed for each patient to screen for MRSA, one from each nostril and one from the perineum. In patients with wounds, an additional swab was taken from the wound surface. In the affected patients octenidine-based products were used in one or two cycles of 7 days each. In addition, adverse events were recorded and the tolerability was assessed using a 4-point scale ranging from 'very good' to 'poor'. RESULTS: Complete decontamination was achieved in 24 patients (67%) following treatment with the octenidine-based products. None of the patients experienced side-effects or secondary symptoms such as skin irritation or allergic reactions during the course of the study. In addition, octenidine was very well tolerated in the majority of patients (n=31; 86%). CONCLUSIONS: The results demonstrate that octenidine-based products are highly efficient in the multifaceted decontamination of hospitalised MRSA-positive patients. Having a range of products that can be used for full body decontamination (including the scalp and nasal passages) is of particular significance when developing an MRSA decontamination protocol, as multiple parts of the body can be affected. Combined with a favourable safety and tolerability profile, octenidine-based products thus represent a good choice in multifaceted MRSA decontamination regimes, which are necessary to curb the increasing problem of severe infections. PMID- 26266564 TI - How I got Leg Club up and running. PMID- 26266565 TI - Tissue Viability Nurse of the Year. BJN Award Runner Up. Nottingham CityCare Tissue Viability Service. PMID- 26266566 TI - Managing venous leg ulcers using compression therapy and dressings. AB - Patient comfort and satisfaction with both compression therapy and wound care are critical to the success of venous leg ulcer treatment. This study observed 22 patients with venous leg ulcers treated over 12 weeks with two-layer compression hosiery and a range of wound dressings. The mean duration of the ulcers was 10.5 months and 48% had a history of recurrent ulcers. Half the ulcers healed within 12 weeks; there was an increase in the proportion of patients reporting 'no impairment' to their mobility, but it was not significant. The ease of donning the two-layer hosiery was rated as excellent or good at 86% of control visits and the ease of doffing at 78%. In 95% of cases the clinicians said they would use the same combination of products again and 73% of patients were satisfied with it. PMID- 26266567 TI - Zinc-impregnated and odour-control two-layer compression. AB - This article presents the results of 40 patients using two versions of a new two layer compression system in a large primary care organisation. The evaluation was undertaken to explore the following areas formulary inclusion consideration: ease of use, clinical acceptability, clinical outcome and additional patient benefits of an alternative new low-profile bandage system containing zinc (n=30) and odour control properties (n=10). PMID- 26266568 TI - Tissue viability services for intravenous drug users. PMID- 26266569 TI - The expense of exudate management. PMID- 26266570 TI - Reducing the pollution risk of pesticide using nano networks induced by irradiation and hydrothermal treatment. AB - Traditional pesticides (TP) often do not adhere tightly to crop foliage. They can easily enter the surrounding environment through precipitation and volatilization. This can result in the pollution of the surrounding soil, water, and air. To reduce pesticide pollution, we developed a loss-control pesticide (LCP) by adding attapulgite with a nano networks structure fabricated using high energy electron beam (HEEB) irradiation and hydrothermal treatment to TP. HEEB irradiation effectively dispersed originally aggregated attapulgite through modified thermal, charge, and physical effects. Hydrothermal treatment further enhanced the dispersion of attapulgite to form nano porous networks via thermal and wet expansion effects, which are beneficial for pesticide binding. An LCP has improved retention on crop leaf surfaces. It has a higher adhesion capacity, reduced leaching and volatilization, and extended residual activity compared with the TP formulation. The treatment increases the residual activity of pesticides on crop foliage and decreases environmental pollution. PMID- 26266571 TI - Monitoring Demineralization and Subsequent Remineralization of Human Teeth at the Dentin-Enamel Junction with Atomic Force Microscopy. AB - Using atomic force microscopy, we monitored the nanoscale surface morphology of human teeth at the dentin-enamel junction after performing successive demineralization steps with an acidic soft drink. Subsequently, we studied the remineralization process with a paste containing calcium and phosphate ions. Repeated atomic force microscopy imaging of the same sample areas on the sample allowed us to draw detailed conclusions regarding the specific mechanism of the demineralization process and the subsequent remineralization process. The about 1 MUm-deep grooves that are caused by the demineralization process were preferentially filled with deposited nanoparticles, leading to smoother enamel and dentine surfaces after 90 min exposure to the remineralizing agent. The deposited material is found to homogeneously cover the enamel and dentine surfaces in the same manner. The temporal evolution of the surface roughness indicates that the remineralization caused by the repair paste proceeds in two distinct successive phases. PMID- 26266572 TI - Hydrogen-Deuterium Exchange Mass Spectrometry Reveals Unique Conformational and Chemical Transformations Occurring upon [4Fe-4S] Cluster Binding in the Type 2 L Serine Dehydratase from Legionella pneumophila. AB - The type 2 L-serine dehydratase from Legionella pneumophila (lpLSD) contains a [4Fe-4S](2+) cluster that acts as a Lewis acid to extract the hydroxyl group of L serine during the dehydration reaction. Surprisingly, the crystal structure shows that all four of the iron atoms in the cluster are coordinated with protein cysteinyl residues and that the cluster is buried and not exposed to solvent. If the crystal structure of lpLSD accurately reflects the structure in solution, then substantial rearrangement at the active site is necessary for the substrate to enter. Furthermore, repair of the oxidized protein when the cluster has degraded would presumably entail exposure of the buried cysteine ligands. Thus, the conformation required for the substrate to enter may be similar to those required for a new cluster to enter the active site. To address this, hydrogen deuterium exchange combined with mass spectrometry (HDX MS) was used to probe the conformational changes that occur upon oxidative degradation of the Fe-S cluster. The regions that show the most significant differential HDX are adjacent to the cluster location in the holoenzyme or connect regions that are adjacent to the cluster. The observed decrease in flexibility upon cluster binding provides direct evidence that the "tail-in-mouth" conformation observed in the crystal structure also occurs in solution and that the C-terminal peptide is coordinated to the [4Fe-4S] cluster in a precatalytic conformation. This observation is consistent with the requirement of an activation step prior to catalysis and the unusually high level of resistance to oxygen-induced cluster degradation. Furthermore, peptide mapping of the apo form under nonreducing conditions revealed the formation of disulfide bonds between C396 and C485 and possibly between C343 and C385. These observations provide a picture of how the cluster loci are stabilized and poised to receive the cluster in the apo form and the requirement for a reduction step during cluster formation. PMID- 26266573 TI - Sustained Changes of Treg and Th17 Cells During Interferon-alpha Therapy in Patients with Chronic Hepatitis B. AB - Chronic hepatitis B (CHB) is a worldwide infectious disease caused by hepatitis B virus (HBV). HBV mainly damages liver cells through immune response. The purpose of this study was to determine whether there were dynamic changes of Treg and Th17 cells and to judge the value of these indicators to antiviral treatment. Twenty-two CHB patients and selected 30 healthy adults were enrolled. Results showed that the expression of Treg (5.72+/-0.46 vs. 4.42+/-0.17, p=0.0019) and Th17 (3.94+/-0.64 vs. 2.66+/-3.12, p=0.0436) cells was significantly increased in CHB patients, as well as the level of interleukin-17 (IL-17) (16.88+/-5.37 vs. 8.59+/-3.31; p=0.004). Then, we monitored longitudinally the impact of the treatment with interferon-alpha and found that the suppression of viral replication induced by interferon-alpha resulted in a decrease in Treg, Th17 cells, and IL-17; we also found that the percentage of Treg and Th17 cells went up without clear evidence of clinical autoimmune disease at the end of treatment. Thus, Treg and Th17 cells might play an important role in interferon-alpha treatment to eliminate HBV. The level of changes may be served to determine the antiviral efficacy of interferon-alpha therapy. PMID- 26266575 TI - 3d-4f {Co(II)3Ln(OR)4} Cubanes as Bio-Inspired Water Oxidation Catalysts. AB - Although the {CaMn4O5} oxygen evolving complex (OEC) of photosystem II is a major paradigm for water oxidation catalyst (WOC) development, the comprehensive translation of its key features into active molecular WOCs remains challenging. The [Co(II)3Ln(hmp)4(OAc)5H2O] ({Co(II)3Ln(OR)4}; Ln = Ho-Yb, hmp = 2 (hydroxymethyl)pyridine) cubane WOC series is introduced as a new springboard to address crucial design parameters, ranging from nuclearity and redox-inactive promoters to operational stability and ligand exchange properties. The {Co(II)3Ln(OR)4} cubanes promote bioinspired WOC design by newly combining Ln(3+) centers as redox-inactive Ca(2+) analogues with flexible aqua-/acetate ligands into active and stable WOCs (max. TON/TOF values of 211/9 s(-1)). Furthermore, they open up the important family of 3d-4f complexes for photocatalytic applications. The stability of the {Co(II)3Ln(OR)4} WOCs under photocatalytic conditions is demonstrated with a comprehensive analytical strategy including trace metal analyses and solution-based X-ray absorption spectroscopy (XAS) investigations. The productive influence of the Ln(3+) centers is linked to favorable ligand mobility, and the experimental trends are substantiated with Born-Oppenheimer molecular dynamics studies. PMID- 26266574 TI - Sources of Health Information Among Select Asian American Immigrant Groups in New York City. AB - Health information can potentially mitigate adverse health outcomes among ethnic minority populations, but little research has examined how minorities access health information. The aim of this study was to examine variations in the use of health information sources among Asian American (AA) subgroups and to identify differences in characteristics associated with the use of these sources. We analyzed data from a foreign-born community sample of 219 Asian Indians, 216 Bangladeshis, 484 Chinese, and 464 Koreans living in New York City. Results found that use of health information sources varied by AA subgroup. Print media source use, which included newspapers, magazines, and/or journals, was highest among Chinese (84%), Koreans (75%), and Bangladeshis (80%), while radio was most utilized by Chinese (48%) and Koreans (38%). Television utilization was highest among Bangladeshis (74%) and Koreans (64%). Koreans (52%) and Chinese (40%) were most likely to use the Internet to access health information. Radio use was best explained by older age and longer time lived in the United States, while print media were more utilized by older individuals. Results also highlighted differences in native-language versus non-native-language media sources for health information by subgroup. Media sources can be used as a vehicle to disseminate health information among AAs. PMID- 26266576 TI - Enhanced Detection of Low-Abundance Host Cell Protein Impurities in High-Purity Monoclonal Antibodies Down to 1 ppm Using Ion Mobility Mass Spectrometry Coupled with Multidimensional Liquid Chromatography. AB - The enormous dynamic range of proteinaceous species present in protein biotherapeutics poses a significant challenge for current mass spectrometry (MS) based methods to detect low-abundance HCP impurities. Previously, an HCP assay based on two-dimensional chromatographic separation (high pH/low pH) coupled to high-resolution quadrupole time-of-flight (QTOF) mass spectrometry and developed in the author's laboratory has been shown to achieve a detection limit of about 50 ppm (parts per milion) for the identification and quantification of HCPs present in monoclonal antibodies following Protein A purification.1 To improve the HCP detection limit we have explored the utility of several new analytical techniques for HCP analysis and thereby developed an improved liquid chromatography-mass spectrometry (LC-MS) methodology for enhanced detection of HCPs. The new method includes (1) the use of a new charge-surface-modified (CSH) C18 stationary phase to mitigate the challenges of column saturation, peak tailing, and distortion that are commonly observed in the HCP analysis; (2) the incorporation of traveling-wave ion mobility (TWIM) separation of coeluting peptide precursors, and (3) the improvement of fragmentation efficiency of low abundance HCP peptides by correlating the collision energy used for precursor fragmentation with their mobility drift time. As a result of these improvements, the detection limit of the new methodology was greatly improved, and HCPs present at a concentration as low as 1 ppm (1 ng HCP/mg mAb) were successfully identified and quantified. The newly developed method was applied to analyze two high-purity mAbs (NIST mAb and Infliximab) expressed in a murine cell line. For both samples, low-abundance HCPs (down to 1 ppm) were confidently identified, and the identities of the HCPs were further confirmed by targeted MS/MS experiments. In addition, the performance of the assay was evaluated by an interlaboratory study in which three independent laboratories performed the same HCP assay on the mAb sample. The reproducibility of this assay is also discussed. PMID- 26266577 TI - All-polymer photonic sensing platform based on whispering-gallery mode microgoblet lasers. AB - We present an all-polymer photonic sensing platform based on whispering-gallery mode microgoblet lasers integrated into a microfluidic chip. The chip is entirely made from polymers, enabling the use of the devices as low-cost disposables. The microgoblet cavities feature quality factors exceeding 10(5) and are fabricated from poly(methyl methacrylate) (PMMA) using spin-coating, mask-based optical lithography, wet chemical etching, and thermal reflow. In contrast to silica based microtoroid resonators, this approach replaces technically demanding vacuum based dry etching and serial laser-based reflow techniques by solution-based processing and parallel thermal reflow. This enables scaling to large-area substrates, and hence significantly reduces device costs. Moreover, the resonators can be fabricated on arbitrary substrate materials, e.g., on transparent and flexible polymer foils. Doping the microgoblets with the organic dye pyrromethene 597 transforms the passive resonators into lasers. Devices have lasing thresholds below 0.6 nJ per pulse and can be efficiently pumped via free space optics using a compact and low-cost green laser diode. We demonstrate that arrays of microgoblet lasers can be readily integrated into a state-of-the-art microfluidic chip replicated via injection moulding. In a proof-of-principle experiment, we show the viability of the lab-on-a-chip via refractometric sensing, demonstrating a bulk refractive index sensitivity (BRIS) of 10.56 nm per refractive index unit. PMID- 26266578 TI - Document Examination: Applications of Image Processing Systems. AB - Dealing with images is a familiar business for an expert in questioned documents: microscopic, photographic, infrared, and other optical techniques generate images containing the information he or she is looking for. A recent method for extracting most of this information is digital image processing, ranging from the simple contrast and contour enhancement to the advanced restoration of blurred texts. When combined with a sophisticated physical imaging system, an image pricessing system has proven to be a powerful and fast tool for routine non destructive scanning of suspect documents. This article reviews frequent applications, comprising techniques to increase legibility, two-dimensional spectroscopy (ink discrimination, alterations, erased entries, etc.), comparison techniques (stamps, typescript letters, photo substitution), and densitometry. Computerized comparison of handwriting is not included. PMID- 26266579 TI - Forensic Science Applications of Ion Mobility Spectrometry. AB - The potential of ion mobility spectrometry (IMS) as a sensitive method for detecting hidden explosives and contraband drugs has been recognized since the advent of the technique twenty years ago. The IMS performed extremely well in laboratory studies of single-component chemical systems, and detection limits of sub-part-per-billion were reported for explosive vapor. However, in order to overcome the problems encountered in monitoring vapors in the ambient atmosphere, special means were needed to increase the sensitivity and specificity of IMS instruments. It took over a decade until single purpose IMS instruments were developed. These portable (or even hand-held) instruments are presently being tested as monitors for detection and identification of drugs or explosives, with sensitivity and specify that are unrivaled by other techniques. PMID- 26266580 TI - Urinary Excretion of Commonly Abused Drugs Following Uncommon Means of Administration. AB - Although abused drugs are administered most often by preferred routes, unconventional routes also may be employed. In addition, unsuspected drug exposure can occur by "unusual" routes, e.g., oral ingestion, passive inhalation, transcutaneous absorption, and in utero exposure. Urine testing is often used to document recent drug exposure. Much of the scientific literature on urine testing concerns studies of conventional routes of drug administration. This article reviews current data on urine testing following unconventional means of administration of drugs of abuse. In each section, a brief review of the principles involved in each unusual route is followed by a discussion of studies and case reports in which urine was tested for drugs of abuse. Special mention is made of the danger of passive inhalation to small children and in utero exposure to fetuses. It is hoped that this review will sensitize those involved in interpretation of urine test data to the many possible ways drugs can enter the human organism. PMID- 26266581 TI - The Use of Microspectrophotometry in the Examination of Paints. AB - With a brief introduction to paint, pigments, color measurement and micro spectrophotometers, this article reviews some of the early applications of microspectrophotometric techniques in forensic science. Practical problems involved in making colour measurements are considered together with the experimental procedures which have been used. The uses which forensic scientists have made of both visible reflectance spectra and colour measurements in casework are discussed, and the advantages over visual comparisons are illustrated. Emphasis is also placed on the use of colour measurements on paint samples recovered from the scene for identifying vehicles involved in hit-and-run accidents. This approach shows advantages in speed as well as specificity over visual comparison. Area which are likely to prove valuable in the future are identified. It seems likely that the use of microtomed thin sections will extend the range of applications of microspectrophotometric techniques for paint examination. PMID- 26266582 TI - Chemical Shielding Anisotropies for Chloroform Exchanging between a Free Site and a Complex with Cryptophane-D: A Cross-Correlated NMR Relaxation Study. AB - The case of (13)C-labeled chloroform exchanging between a free site in solution and the encaged site within the cryptophane-D cavity is investigated using the measurements of longitudinal cross-correlated relaxation rates, involving the interference of the dipole-dipole and chemical shielding anisotropy interactions. A compact theoretical expression is provided, along with an experimental protocol, based on INEPT (insensitive nuclei enhanced by polarization)-enhanced double-quantum-filtered inversion recovery measurements. The analysis of the build-up curves results in a set of cross-correlated relaxation rates for both the (13)C and (1)H spins at the two sites. It is demonstrated that the results can be given a consistent interpretation in terms of molecular-level properties, such as rotational correlation times, the Lipari-Szabo order parameter, and interaction strength constants. The analysis yields the bound-site carbon-13 chemical shielding anisotropy, DeltasigmaC = -58 +/- 8 ppm, in good agreement with most recent liquid-crystal measurements and the corresponding proton shielding anisotropy, DeltasigmaH = 14 +/- 2 ppm. PMID- 26266583 TI - An unusual density evolution between SrCdB2O5 polymorphs. AB - Owing to the effect of atomic vibrations, a high-temperature phase usually features a relatively smaller density when compared with a low-temperature phase. In this work, a new SrCdB2O5 phase has been discovered. According to the crystallization temperature from low to high, the new SrCdB2O5 phase can be regarded as the high-temperature beta-SrCdB2O5 phase. The density of beta SrCdB2O5 is obviously larger than that of alpha-SrCdB2O5, meanwhile beta-SrCdB2O5 is energetically favored. This unusual density evolution phenomenon has been investigated. In addition, the Pb(2+)-doped compounds, PbxSr1-xCdB2O5 (x = 0.125, 0.25, 0.375, 0.5), have also been investigated by powder refinement. PMID- 26266584 TI - Conformation-Selective Resonant Photoelectron Spectroscopy via Dipole-Bound States of Cold Anions. AB - Molecular conformation is important in chemistry and biochemistry. Conformers connected by low energy barriers can only be observed at low temperatures and are difficult to be separated. Here we report a new method to obtain conformation selective spectroscopic information about dipolar molecular radicals via dipole bound excited states of the corresponding anions cooled in a cryogenic ion trap. We observed two conformers of cold 3-hydroxyphenoxide anions [m-HO(C6H4)O(-)] in high-resolution photoelectron spectroscopy and measured different electron affinities, 18,850(8) and 18,917(5) cm(-1), for the syn and anti 3-hydroxyphenoxy radicals, respectively. We also observed dipole-bound excited states for m HO(C6H4)O(-) with different binding energies for the two conformers due to the different dipole moments of the corresponding 3-hydroxyphenoxy radicals. Excitations to selected vibrational levels of the dipole-bound states result in conformation-selective photoelectron spectra. This method should be applicable to conformation-selective spectroscopic studies of any anions with dipolar neutral cores. PMID- 26266585 TI - Distinguishing the Effects of Bond-Length Alternation versus Bond-Order Alternation on the Nonlinear Optical Properties of pi-Conjugated Chromophores. AB - Understanding the relationships between the molecular nonlinear optical (NLO) properties and the bond-length alternation (BLA) or pi-bond-order alternation (BOA) along the molecular backbone of linear pi-conjugated systems has proven widely useful in the development of NLO organic chromophores and materials. Here, we examine model polymethines to elucidate the reliability of these relationships. While BLA is solely a measure of molecular geometric structure, BOA includes information pertaining to the electronic structure. As a result, BLA is found to be a good predictor of NLO properties only when optimized geometries are considered, whereas BOA is more broadly applicable. Proper understanding of the distinction between BLA and BOA is critical when designing computational studies of NLO properties, especially for molecules in complex environments or in nonequilibrium geometries. PMID- 26266586 TI - Porous Carbon Mat as an Electrochemical Testing Platform for Investigating the Polysulfide Retention of Various Cathode Configurations in Li-S Cells. AB - Two optimized cathode configurations (a porous current collector and an interlayer) are utilized to determine the better architecture for improving the cycle stability and reversibility of lithium-sulfur (Li-S) cells. The electrochemical analysis on the upper-plateau discharge capacity (QH) and the lower-plateau discharge capacity (QL) is introduced for assessing, respectively, the polysulfide retention and the electrochemical reactivity of the cell. The analysis results in line with the expected materials chemistry principles suggest that the interlayer configuration offers stable cell performance for sulfur cathodes. The significance of the interlayer is to block the free migration of the dissolved polysulfides, which is a key factor for immobilizing and continuously utilizing the active material in sulfur cathodes. Accordingly, the carbon mat interlayers provide sulfur cathodes with a high discharge capacity of 864 mA h g(-1) at 1 C rate with a high capacity retention rate of 61% after 400 cycles. PMID- 26266587 TI - Conformation of Capping Ligands on Nanoplates: Facet-Edge-Induced Disorder and Self-Assembly-Related Ordering Revealed by Sum Frequency Generation Spectroscopy. AB - Surface-curvature-amplified conformational disorder in alkyl capping ligands has been observed previously when the nanoparticle radii approach the ligand length. Herein, sum frequency generation studies on oleic-acid-capped nanoplates show that even on faceted surfaces with dimensions tens of times greater than the ligand length a significant proportion of gauche defects exist in the capping layer. The molecular disorder on the nanosized facets is attributed to a facet edge effect, which is diminished when increasing the facet size or assembling the nanofacets side to side. This feature is further explored to probe the self assembly dynamics of nanoplates. PMID- 26266588 TI - Nonepitaxial Thin-Film InP for Scalable and Efficient Photocathodes. AB - To date, some of the highest performance photocathodes of a photoelectrochemical (PEC) cell have been shown with single-crystalline p-type InP wafers, exhibiting half-cell solar-to-hydrogen conversion efficiencies of over 14%. However, the high cost of single-crystalline InP wafers may present a challenge for future large-scale industrial deployment. Analogous to solar cells, a thin-film approach could address the cost challenges by utilizing the benefits of the InP material while decreasing the use of expensive materials and processes. Here, we demonstrate this approach, using the newly developed thin-film vapor-liquid-solid (TF-VLS) nonepitaxial growth method combined with an atomic-layer deposition protection process to create thin-film InP photocathodes with large grain size and high performance, in the first reported solar device configuration generated by materials grown with this technique. Current-voltage measurements show a photocurrent (29.4 mA/cm(2)) and onset potential (630 mV) approaching single crystalline wafers and an overall power conversion efficiency of 11.6%, making TF VLS InP a promising photocathode for scalable and efficient solar hydrogen generation. PMID- 26266589 TI - Calculating NMR Chemical Shifts for Paramagnetic Metal Complexes from First Principles. AB - Paramagnetic effects on NMR shifts (pNMR) for paramagnetic metal complexes are calculated from first-principles, without recourse to spin Hamiltonian parameters. A newly developed code based on complete active space (CAS) and restricted active space (RAS) techniques in conjunction with treating spin-orbit (SO) coupling via state interaction is applied to (13)C NMR shifts of actinyl tris-carbonate complexes, specifically [UO2(CO3)3](5-) and [NpO2(CO3)3](4-). The experimental pNMR shifts as well as the sizable difference of the (13)C NMR shift for these iso-electronic species are well reproduced by the calculations. Approximations to the pNMR shift equations using spin Hamiltonian parameters or the magnetic susceptibility are calculated for the same systems at the same level of theory, and it is shown how the approximations relate to the ab initio data. PMID- 26266590 TI - Fluctuating Dynamics of Nanoscale Chemical Oscillations: Theory and Experiments. AB - Chemical oscillations are observed in a variety of reactive systems, including biological cells, for the functionality of which they play a central role. However, at such scales, molecular fluctuations are expected to endanger the regularity of these behaviors. The question of the mechanism by which robust oscillations can nevertheless emerge is still open. In this work, we report on the experimental investigation of nanoscale chemical oscillations observed during the NO2 + H2 reaction on platinum, using field electron microscopy. We show that the correlation time and the variance of the period of oscillations are connected by a universal constraint, as predicted theoretically for systems subjected to a phenomenon called phase diffusion. These results open the way to a better understanding, modeling, and control of nanoscale oscillators. PMID- 26266591 TI - Directing Anisotropic Assembly of Metallic Nanoclusters by Exploiting Linear Trio Interactions and Quantum Size Effects: Au Chains on Ag(100) Thin Films. AB - Discovery and understanding of mechanisms for kinetically controlled growth of metal nanoclusters can be enabled by realistic atomistic-level modeling with ab initio kinetics. KMC simulation of such a model for Au deposition on Ag(100) films reveals the formation of single-atom-wide Au chains below 275 K, even though 2D islands are thermodynamically preferred. Chain formation is shown to reflect a combination of strong linear trio attractions guiding assembly and a weak driving force and slow rate of transformation of 1D chains to 2D islands (or sometimes irreversible rounding of adatoms from chain sides to ends). Behavior can also be tuned by quantum size effects: chain formation predominates on 2 monolayer Ag(100) films supported on NiAl(100) at 250 K for low coverages but not on 1- or 3-monolayer films, and longer chains form than on bulk Ag(100). Our predictive kinetic modeling shows the potential for simulation-guided discovery and analysis of novel self-assembly processes. PMID- 26266592 TI - Environmental Effects on the Photophysics of Organic-Inorganic Halide Perovskites. AB - The photophysical properties of films of organic-inorganic lead halide perovskites under different ambient conditions are herein reported. We demonstrate that their luminescent properties are determined by the interplay between photoinduced activation and darkening processes, which strongly depend on the atmosphere surrounding the samples. We have isolated oxygen and moisture as the key elements in each process, activation and darkening, both of which involve the interaction with photogenerated carriers. These findings show that environmental factors play a key role in the performance of lead halide perovskites as efficient luminescent materials. PMID- 26266593 TI - Organic-Inorganic Composites of Semiconductor Nanocrystals for Efficient Excitonics. AB - Nanocomposites of colloidal semiconductor nanocrystals integrated into conjugated polymers are the key to soft-material hybrid optoelectronics, combining advantages of both plastics and particles. Synergic combination of the favorable properties in the hybrids of colloidal nanocrystals and conjugated polymers offers enhanced performance and new functionalities in light-generation and light harvesting applications, where controlling and mastering the excitonic interactions at the nanoscale are essential. In this Perspective, we highlight and critically consider the excitonic interactions in the organic-inorganic nanocomposites to achieve highly efficient exciton transfer through rational design of the nanocomposites. The use of strong excitonic interactions in optoelectronic devices can trigger efficiency breakthroughs in hybrid optoelectronics. PMID- 26266594 TI - Ultrafast Dynamics of Carboxy-Hemoglobin: Two-Dimensional Infrared Spectroscopy Experiments and Simulations. AB - This Letter presents a comparison between experimental and simulated 2D mid infrared spectra of carboxy-hemoglobin in the spectral region of the carbon monoxide stretching mode. The simulations rely on a fluctuating potential energy surface that includes both the effect of heme and the protein surroundings computed from molecular dynamics simulations. A very good agreement between theory and experiment is obtained with no adjustable parameters. The simulations show that the effect of the distal histidine through the hydrogen bond is strong and is directly responsible for the slow decay of the frequency-frequency correlation function on a 10 ps time scale. This study confirms that fluctuations in carboxy-hemoglobin are more inhomogeneous than those in the more frequently studied carboxy-myoglobin. The comparison between simulations and experiments brings valuable information on the complex relation between protein structure and spectral diffusion. PMID- 26266595 TI - Ferroelectric Polarization of CH3NH3PbI3: A Detailed Study Based on Density Functional Theory and Symmetry Mode Analysis. AB - Ferroelectricity in halide perovskites currently represents a crucial issue, as it may have an important role for the enhancement of solar cells efficiency. Simulations of ferroelectric properties based on density functional theory are conceptually more demanding compared with "conventional" inorganic ferroelectrics due to the presence of both organic and inorganic components in the same compound. Here we present a detailed study focused on the prototypical CH3NH3PbI3 perovskite. By using density functional theory combined with symmetry mode analysis, we disentangle the contributions of the methylammonium cations and the role of the inorganic framework, therefore suggesting possible routes to enhance the polarization in this compound. Our estimate of the polarization for the tetragonal phase at low temperature is ~4.42 MUC/cm(2), which is substantially lower than that of traditional perovskite oxides. PMID- 26266596 TI - Toward Controlled Growth of Helicity-Specific Carbon Nanotubes. AB - The underlying mechanisms for the nucleation of carbon nanotubes as well as their helicity, remain elusive. Here, using van der Waals dispersion force calculations implemented within density functional theory, we study the cap formation, believed to be responsible for the chirality of surface-catalyzed carbon nanotubes. We find the energetics associated with growth along different facets to be independent of the surface orientation and that the growth across an edge along the axis of the metal particle leads to a perfect honeycomb lattice in a curved geometry. The formation of defects in the graphene matrix, which bend the carbon plane, requires that two or more graphene embryos with significantly different growth axis merge. Such scenario is only possible at the front- or back end of the metal particle where growth symmetry is broken. The graphene embryos reconstruct their hexagonal structure into pentagons, heptagons, and octagons counterpart to accommodate the tube curvature. PMID- 26266597 TI - Pedestrian Guide to Symmetry Properties of the Reference Cubic Structure of 3D All-Inorganic and Hybrid Perovskites. PMID- 26266598 TI - Mechanism of Decomposition of Surface Ethoxy Species to Ethene and Acidic OH Groups on H-ZSM-5. AB - The reaction mechanism of the decomposition of ethoxy species to ethene and acidic OH groups on H-ZSM-5 was studied by IR spectroscopy using isotope-labeled ethanol. The concerted mechanism occurring on both the ethoxy (acid) site and the counterpart lattice oxygen was suggested by GC-MS analysis of evolved d2-ethene and IR observation of the recovery of OH s groups on acid sites from the decomposition of CH3CD2O- ethoxy species. The concerted mechanism was further confirmed by the estimation of activation energy for decomposition of CH3CH2O-, CH3CD2O-, and CD3CD2O- ethoxy species, 122 +/- 3, 125 +/- 3, and 140 +/- 5 kJ mol(-1), respectively, where the kinetic isotope effect was observed for the cleavage of the CH or CD bond of the methyl group of the ethoxy species. PMID- 26266599 TI - Stabilization of Mixed Frenkel-Charge Transfer Excitons Extended Across Both Strands of Guanine-Cytosine DNA Duplexes. AB - The photoreactive pathways that may lead to DNA damage depend crucially upon the nature of the excited electronic states. The study of alternating guanine cytosine duplexes by fluorescence spectroscopy and quantum mechanical calculations identifies a novel type of excited states that can be populated following UVB excitation. These states, denoted High-energy Emitting Long-lived Mixed (HELM) states, extend across both strands and arise from mixing between cytosine Frenkel excitons and guanine-to-cytosine charge transfer states. They emit at energies higher than pipi* states localized on single bases, survive for several nanoseconds, are sensitive to the ionic strength of the solution, and are strongly affected by the structural transition from the B form to the Z form. Their impact on the formation of lesions of the genetic code needs to be assessed. PMID- 26266600 TI - Nanostructured Metal Carbides for Aprotic Li-O2 Batteries: New Insights into Interfacial Reactions and Cathode Stability. AB - The development of nonaqueous Li-oxygen batteries, which relies on the reversible reaction of Li + O2 to give lithium peroxide (Li2O2), is challenged by several factors, not the least being the high charging voltage that results when carbon is typically employed as the cathode host. We report here on the remarkably low 3.2 V potential for Li2O2 oxidation on a passivated nanostructured metallic carbide (Mo2C), carbon-free cathode host. Online mass spectrometry coupled with X ray photoelectron spectroscopy unequivocally demonstrates that lithium peroxide is simultaneously oxidized together with the Li(x)MoO3-passivated conductive interface formed on the carbide, owing to their close redox potentials. The process rejuvenates the surface on each cycle upon electrochemical charge by releasing Li(x)MoO3 into the electrolyte, explaining the low charging potential. PMID- 26266601 TI - Exploiting Fast Exciton Diffusion in Dye-Doped Polymer Nanoparticles to Engineer Efficient Photoswitching. AB - Photoswitching of bright fluorescent nanoparticles opens new possibilities for bioimaging with superior temporal and spatial resolution. However, efficient photoswitching of nanoparticles is hard to achieve using Forster resonance energy transfer (FRET) to a photochromic dye, because the particle size is usually larger than the Forster radius. Here, we propose to exploit the exciton diffusion within the FRET donor dyes to boost photoswitching efficiency in dye-doped polymer nanoparticles. To this end, we utilized bulky hydrophobic counterions that prevent self-quenching and favor communication of octadecyl rhodamine B dyes inside a polymer matrix of poly(D,L-lactide-co-glycolide). Among tested counterions, only perfluorinated tetraphenylborate that favors the exciton diffusion enables high photoswitching efficiency (on/off ratio ~20). The switching improves with donor dye loading and requires only 0.1-0.3 wt % of a diphenylethene photochromic dye. Our nanoparticles were validated both in solution and at the single-particle level. The proposed concept paves the way to new efficient photoswitchable nanomaterials. PMID- 26266602 TI - Less Is More: The Case of Metal Cocatalysts. AB - We provide evidence that for a multielectron reaction such as hydrogen reduction, the photocatalyst design should include only a single cocatalytic site per each segment of the semiconductor capable of light excitation. This is to ensure that intermediates are formed at close proximity. These findings are demonstrated by evaluating the efficiency for hydrogen production over a nanoparticle-based photocatalyst consisting of Pt-decorated CdSe@CdS rods. Rods decorated with a single Pt catalyst were found to be the most active for hydrogen production, with QE of 27%, while rods having two reduction sites reached QE of only 18% and rods with multiple sites showed very low activity. The advantage of using a single catalytic site became negligible when the rods were employed in catalyzing a single electron reaction. We believe the implications of this finding are of significance for the proper design of photocatalysts aimed at solar-to-fuel energy conversion. PMID- 26266603 TI - Molecular Design for Tuning Work Functions of Transparent Conducting Electrodes. AB - In this Perspective, we provide a brief background on the use of aromatic phosphonic acid modifiers for tuning work functions of transparent conducting oxides, for example, zinc oxide (ZnO) and indium tin oxide (ITO). We then introduce our preliminary results in this area using conjugated phosphonic acid molecules, having a substantially larger range of dipole moments than their unconjugated analogues, leading to the tuning of ZnO and ITO electrodes over a 2 eV range as derived from Kelvin probe measurements. We have found that these work function changes are directly correlated to the magnitude and the direction of the computationally derived molecular dipole of the conjugated phosphonic acids, leading to the predictive power of computation to drive the synthesis of new and improved phosphonic acid ligands. PMID- 26266604 TI - Catechol and HCl Adsorption on TiO2(110) in Vacuum and at the Water-TiO2 Interface. AB - Coadsorbed water is often unavoidable in electrochemistry and low-temperature catalysis. In addition, water influences the adsorption of biomolecules on surfaces. We use ab initio DFT molecular dynamics and ground-state calculations to study the adsorption of HCl and catechol on the rutile TiO2(110) surface and at a water-rutile interface. We find that a coadsorbed water film reduces the adsorption energy of both catechol and HCl significantly because water molecules must be displaced from the surface before catechol or HCl can adsorb. The adsorption energy of catechol (or HCl) at the water-rutile interface can be estimated as the adsorption energy in vacuum minus the energy to remove two water molecules (respectively, one water molecule) from the rutile surface in vacuum and place them in liquid water. This estimate predicts the effect of a surface water film on adsorption without the need of molecular dynamics. PMID- 26266605 TI - Single Nanoparticle-Based Heteronanojunction as a Plasmon Ruler for Measuring Dielectric Thin Films. AB - Nondestructive, noninvasive and accurate measurement of thin film thicknesses on dielectric substrates is challenging. In this work a ruler for measuring thin film thicknesses utilizes the heteronanojunction construct formed between a plasmonic nanoparticle and a high refractive index nonplasmonic substrate. The high near-field sensitivity in the nanojunction renders it suitable for measuring the thickness of intervening dielectric thin films. We demonstrate this by controlling the thickness of dielectric spacer layers created by overgrowing SiO2 thin films on commercially available silicon substrates. While Rayleigh (using dark-field) scattering measurements show that the spectral response is well correlated to the thickness of SiO2 spacer layers the distance-dependence is much steeper with surface-enhanced Raman scattering (SERS). Good agreement between 3D simulations and experimental results confirm the plasmon ruler construct's sensitivity to the dielectric thin film spacing. Thus, we postulate that this single nanoparticle based heteronanojunction configuration can serve as a convenient and simple ruler in metrology of thin films as well as a platform for SERS-based detection even in cases where plasmonically active films are not a suitable substrate. PMID- 26266606 TI - Methane Activation by Iron-Carbide Cluster Anions FeC6(-). AB - Laser-ablation-generated and mass-selected iron-carbide cluster anions FeC6(-) were reacted with CH4 in a linear ion trap reactor under thermal collision conditions. The reactions were characterized by mass spectrometry and density functional theory calculations. Adsorption product of FeC6CH4(-) was observed in the experiments. The identified large kinetic isotope effect suggests that CH4 can be activated by FeC6(-) anions with a dissociative adsorption manner, which is further supported by the reaction mechanism calculations. The large dipole moment of FeC6(-) (19.21 D) can induce a polarization of CH4 and can facilitate the cleavage of C-H bond. This study reports the CH4 activation by transition metal carbide anions, which provides insights into mechanistic understanding of iron-carbon centers that are important for condensed-phase catalysis. PMID- 26266607 TI - Crystal Morphologies of Organolead Trihalide in Mesoscopic/Planar Perovskite Solar Cells. AB - The crystal morphology of organolead trihalide perovskite (OTP) light absorbers can have profound influence on the perovskite solar cells (PSCs) performance. Here we have used a combination of conventional transmission electron microscopy (TEM) and high-resolution TEM (HRTEM), in cross-section and plan-view, to characterize the morphologies of a solution-processed OTP (CH3NH3PbI3 or MAPbI3) within mesoporous TiO2 scaffolds and within capping and planar layers. Studies of TEM specimens prepared with and without the use of focused ion beam (FIB) show that FIBing is a viable method for preparing TEM specimens. HRTEM studies, in conjunction with quantitative X-ray diffraction, show that MAPbI3 perovskite within mesoporous TiO2 scaffold has equiaxed grains of size 10-20 nm and relatively low crystallinity. In contrast, the grain size of MAPbI3 perovskite in the capping and the planar layers can be larger than 100 nm in our PSCs, and the grains can be elongated and textured, with relatively high crystallinity. The observed differences in the performance of planar and mesoscopic-planar hybrid PSCs can be attributed in part to the striking differences in their perovskite grain morphologies. PMID- 26266608 TI - Disentangling the Contribution of Multiple Isomers to the Infrared Spectrum of the Protonated Water Heptamer. AB - We use infrared/infrared double-resonance population labeling (IR(2)MS(2)) spectroscopy in the spectral region of the free and hydrogen-bonded OH stretching fundamentals (2880-3850 cm(-1)) to identify the number and to isolate the vibrational signatures of individual isomers contributing to the gas-phase IR spectra of the cryogenically cooled protonated water clusters H(+)(H2O)n.H2/D2 with n = 7-10. For n = 7, four isomers are identified and assigned. Surprisingly, the IR(2)MS(2) spectra of the protonated water octa-, nona-, and decamer show no evidence for multiple isomers. The present spectra support the prediction that the quasi-2D to 3D structural transition occurs in between n = 8 and 9 in the cold cluster regime. However, the same models have difficulty explaining the remarkable size dependence of the isomer population reported here. PMID- 26266609 TI - Two-Dimensional Vanadium Carbide (MXene) as Positive Electrode for Sodium-Ion Capacitors. AB - Ion capacitors store energy through intercalation of cations into an electrode at a faster rate than in batteries and within a larger potential window. These devices reach a higher energy density compared to electrochemical double layer capacitor. Li-ion capacitors are already produced commercially, but the development of Na-ion capacitors is hindered by lack of materials that would allow fast intercalation of Na-ions. Here we investigated the electrochemical behavior of 2D vanadium carbide, V2C, from the MXene family. We investigated the mechanism of Na intercalation by XRD and achieved capacitance of ~100 F/g at 0.2 mV/s. We assembled a full cell with hard carbon as negative electrode, a known anode material for Na ion batteries, and achieved capacity of 50 mAh/g with a maximum cell voltage of 3.5 V. PMID- 26266610 TI - Water on the MgO(001) Surface: Surface Reconstruction and Ion Solvation. AB - The interaction of water with the MgO(001) surface under ambient conditions is investigated by density functional theory combined with statistical thermodynamics. For water loadings of more than one monolayer, we show that the standard structure model, a fully hydroxylated surface, needs to be revised. Reconstructed surfaces, involving hydrated/hydroxylated Mg(2+) ions above the surface, are more stable. These findings provide a consistent picture for surface hydroxylation between low and high water coverage that is in agreement with available XPS data. PMID- 26266611 TI - Trend of Perovskite Solar Cells: Dig Deeper to Build Higher. PMID- 26266612 TI - Pancake pi-pi Bonding Goes Double: Unexpected 4e/All-Sites Bonding in Boron- and Nitrogen-Doped Phenalenyls. AB - Chemical bonding interactions are the main driving force for the formation of molecules and materials from atoms. The two-electron/multicenter pancake pi-pi bonding found in phenalenyl (PLY, 1) radical pi-dimers is intriguing due to its unconventional nature of covalent bonding for molecular aggregations and its propensity to induce unique optical, electronic, and magnetic properties. By using high-level quantum chemistry calculations, we show that the B- or N-doped PLYs (2 and 4), usually considered closed-shell and therefore trifling, can be rendered open-shell singlet by proper edge substitutions (3 and 5). The resulting two unpaired valence electrons on each molecular unit contribute to the formation of a genuine pancake-shaped 4e/all-sites double pi-pi bonding upon intermolecular pi-dimerization, in contrast to the 2e/half-sites single pi-pi bonding in the parent PLY pi-dimers. The unusual double pi-pi bonding motif discovered in these PLY analogues may broaden the landscape of, and find new applications for, intermolecular covalent bonding interactions. PMID- 26266613 TI - Photoinduced Reversible Structural Transformations in Free-Standing CH3NH3PbI3 Perovskite Films. AB - In the pursuit to better understand the mechanisms of perovskite solar cells we performed Raman and photoluminescence measurements of free-standing CH3NH3PbI3 films, comparing dark with working conditions. The films, grown on a glass substrate and sealed by a thin glass coverslip, were measured subsequent to dark and white-light pretreatments. The extremely slow changes we observe in both the Raman and photoluminescence cannot be regarded as electronic processes, which are much faster. Thus, the most probable explanation is of slow photoinduced structural changes. The CH3NH3PbI3 transformation between the dark and the light structures is reversible, with faster rates for the changes under illumination. The results seem to clarify several common observations associated with solar cell mechanisms, like performance improvement under light soaking. More important is the call for solar-cell-related investigation of CH3NH3PbI3 to take the photoinduced structural changes into consideration when measuring and interpreting the results. PMID- 26266614 TI - LHCII Populations in Different Quenching States Are Present in the Thylakoid Membranes in a Ratio that Depends on the Light Conditions. AB - LHCII is the major antenna complex of plants and algae, where it is involved in light harvesting and photoprotection. Its properties have been extensively studied in vitro, after isolation of the pigment-protein complex from the membranes, but are these properties representative for LHCII in the thylakoid membrane? In this work, we have studied LHCII in the cells of the green alga C. reinhardtii acclimated to different light conditions in the absence of the other components of the photosynthetic apparatus. We show that LHCII exists in the membranes in different fluorescence quenching states, all having a shorter excited-state lifetime than isolated LHCII in detergent. The ratio between these populations depends on the light conditions, indicating that the light is able to regulate the properties of the complexes in the membrane. PMID- 26266615 TI - Design and Preparation of Supported Au Catalyst with Enhanced Catalytic Activities by Rationally Positioning Au Nanoparticles on Anatase. AB - A synergistic effect between individual components is crucial for increasing the activity of metal/metal oxide catalysts. The greatest challenge is how to control the synergistic effect to obtain enhanced catalytic performance. Through density functional theory calculations of model Au/TiO2 catalysts, it is suggested that there is strong interaction between Au nanoparticles and Ti species at the edge/corner sites of anatase, which is favorable for the formation of stable oxygen vacancies. Motivated by this theoretical analysis, we have rationally prepared Au nanoparticles attached to edge/corner sites of anatase support (Au/TiO2-EC), confirmed by their HR-TEM images. As expected, this strong interaction is well characterized by Raman, UV-visible, and XPS techniques. Very interestingly, compared with conventional Au catalysts, Au/TiO2-EC exhibits superior catalytic activity in the oxidations using O2. Our approach to controlling Au nanoparticle positioning on anatase to obtain enhanced catalytic activity offers an efficient strategy for developing more novel supported metal catalysts. PMID- 26266616 TI - Identification of Trap States in Perovskite Solar Cells. AB - Thermally stimulated current (TSC) measurements are used to characterize electronic trap states in methylammonium lead iodide perovsite solar cells. Several TSC peaks were observed over the temperature range from 20 K to room temperature. To elucidate the origins of these peaks, devices with various organic charge transport layers and devices without transport layers were tested. Two peaks appear at very low temperatures, indicating shallow trap states that are mainly attributed to the PCBM/C60 electron transport bilayer. However, two additional peaks appear at higher temperatures, that is, they are deeper in energy, and are assigned to the perovskite layer. At around T = 163 K, a sharp peak, also present in the dark TSC measurements, is assigned to the orthorhombic tetragonal phase transition in the perovskite. However, a peak at around T = 191 K is assigned to trap states with activation energies of around 500 meV but with a rather low concentration of 1 * 10(21) m(-3). PMID- 26266617 TI - Efficient Carrier Separation and Intriguing Switching of Bound Charges in Inorganic-Organic Lead Halide Solar Cells. AB - We fabricated a mesoporous perovskite solar cell with a ~14% conversion efficiency, and we investigated its beneficial grain boundary properties of the perovskite solar cells through the use of scanning probe microscopy. The CH3NH3Pb(I0.88,Br0.12)3 showed a significant potential barrier bending at the grain boundary and induced passivation. The potential difference value in the x = 0.00 sample is ~50 mV, and the distribution of the positive potential is lower than that of the x = 0.12 sample. We also investigated the polarization and hysteretic properties of the perovskite thin films by measuring the local piezoresponse. Specifically, the charged grain boundaries play a beneficial role in electron-hole depairing and in suppressing recombination in order to realize high-efficiency perovskite solar cells. PMID- 26266618 TI - Crystalline LiN5 Predicted from First-Principles as a Possible High-Energy Material. AB - The search for stable polymeric nitrogen and polynitrogen compounds has attracted great attention due to their potential applications as high-energy-density materials. Here we report a theoretical prediction of an interesting LiN5 crystal through first-principles calculations and unbiased structure searching techniques. Theoretical calculations reveal that crystalline LiN5 is thermodynamically stable at pressures above 9.9 GPa, and remains metastable at ambient conditions. The metastability of LiN5 stems from the inherent stability of the N5(-) anions and strong anion-cation interactions. It is therefore possible to synthesize LiN5 by compressing solid LiN3 and N2 gas under high pressure and quench recover the product to ambient conditions. To the best of our knowledge, this is the first time that stable N5(-) anions are predicted in crystalline states. The weight ratio of nitrogen in LiN5 is nearly 91%, placing LiN5 as a promising high-energy material. The decomposition of LiN5 is expected to be highly exothermic, releasing an energy of approximately 2.72 kJ.g(-1). The present results open a new avenue to synthesize polynitrogen compounds and provide a key perspective toward the understanding of novel chemical bonding in nitrogen-rich compounds. PMID- 26266619 TI - Beyond Shockley-Queisser: Molecular Approaches to High-Efficiency Photovoltaics. AB - Molecular materials afford abundant flexibility in the tunability of physical and electronic properties. As such, they are ideally suited to engineering low-cost, flexible, light-harvesting materials that break away from the single-threshold paradigm. Single-threshold solar cells are capable of harvesting a maximum of 33.7% of incident sunlight, whereas two-threshold cells are capable of energy harvesting efficiencies exceeding 45%. In this Perspective, we provide the theoretical background with which upper efficiency limits for various multiple threshold solar cell architectures may be calculated and review and discuss various reports that employ processes such as triplet-triplet annihilation and singlet fission in multiple-threshold devices comprised of molecular materials. PMID- 26266620 TI - Effect of Ultrahigh Stiffness of Defective Graphene from Atomistic Point of View. AB - Well-known effects of mechanical stiffness degradation under the influence of point defects in macroscopic solids can be controversially reversed in the case of low-dimensional materials. Using atomistic simulation, we showed here that a single-layered graphene film can be sufficiently stiffened by monovacancy defects at a tiny concentration. Our results correspond well with recent experimental data and suggest that the effect of mechanical stiffness augmentation is mainly originated from specific bonds distribution in the surrounded monovacancy defects regions. We showed that such unusual mechanical response is the feature of presence of specifically monovacancies, whereas other types of point defects such as divacancy, 555-777 and Stone-Wales defects, lead to the ordinary degradation of the graphene mechanical stiffness. PMID- 26266621 TI - Radical Reactivity in the Condensed Phase: Intermolecular versus Intramolecular Reactions of Alkoxy Radicals. AB - Condensed-phase alkoxy (RO) radicals can undergo unimolecular (e.g., intramolecular H atom abstraction) reactions as well as bimolecular (intermolecular H atom abstraction) reactions, though the competition between these two channels is not well constrained. Here, we examine this branching by generating RO radicals from the photolysis of a large alkyl nitrite (C20H41ONO) in hexanes and nebulizing the mixture into an aerosol mass spectrometer for analysis. Product ions associated with unimolecular (isomerization) reactions were observed to increase upon photolysis. However, no formation of the C20 alcohol (C20H41OH, the expected product from RO + RH reactions) was observed, suggesting that bimolecular reactions are at most a minor channel for this condensed-phase system (involving saturated hydrocarbons). This result, combined with previous studies of liquid-phase RO radicals carried out at higher concentrations, suggests that when 1,5-H atom abstraction reactions are facile (i.e., in which a 1,5-H atom shift from a secondary or tertiary carbon can occur), this channel will dominate over bimolecular reactions. PMID- 26266622 TI - Crucial Role of Nuclear Dynamics for Electron Injection in a Dye-Semiconductor Complex. AB - We investigate the electron injection from a terrylene-based chromophore to the TiO2 semiconductor bridged by a recently proposed phenyl-amide-phenyl molecular rectifier. The mechanism of electron transfer is studied by means of quantum dynamics simulations using an extended Huckel Hamiltonian. It is found that the inclusion of the nuclear motion is necessary to observe the photoinduced electron transfer. In particular, the fluctuations of the dihedral angle between the terrylene and the phenyl ring modulate the localization and thus the electronic coupling between the donor and acceptor states involved in the injection process. The electron propagation shows characteristic oscillatory features that correlate with interatomic distance fluctuations in the bridge, which are associated with the vibrational modes driving the process. The understanding of such effects is important for the design of functional dyes with optimal injection and rectification properties. PMID- 26266623 TI - C60 as an Efficient n-Type Compact Layer in Perovskite Solar Cells. AB - Organic-inorganic halide perovskite solar cells have rapidly evolved over the last 3 years. There are still a number of issues and open questions related to the perovskite material, such as the phenomenon of anomalous hysteresis in current-voltage characteristics and long-term stability of the devices. In this work, we focus on the electron selective contact in the perovskite solar cells and physical processes occurring at that heterojunction. We developed efficient devices by replacing the commonly employed TiO2 compact layer with fullerene C60 in a regular n-i-p architecture. Detailed spectroscopic characterization allows us to present further insight into the nature of photocurrent hysteresis and charge extraction limitations arising at the n-type contact in a standard device. Furthermore, we show preliminary stability data of perovskite solar cells under working conditions, suggesting that an n-type organic charge collection layer can increase the long-term performance. PMID- 26266624 TI - Determination of ion pairing on capping structures of gold nanoparticles by phase extraction. AB - As nanoparticles with different capping structures in solution phases have found widespread applications of wide interest, understanding how the capping structure change influences their presence in phases or solutions is important for gaining full control over both the intended nanoactivity and the unintended nanotoxicity. This report describes a simple and effective phase extraction method for analyzing the degree of ion pairing in the capping molecular structure of nanoparticles. Gold nanoparticles of a few nanometers diameter with a mixed monolayer capping structure consisting of both hydrophobic and hydrophilic and reactive groups were studied as a model system, and a quantitative model was derived based on chemical equilibria in a two-phase system, and used to assess the experimental data for phase extraction by cationic species. In contrast to the traditional perception of 100% ion pairing, only a small fraction (~20%) of the negatively-charged groups was found to be responsible for the phase extraction. The viability of using this phase extraction method for analyzing the degree of ion-pairing in the capping molecular structure of different nanoparticles is also discussed, which has implications for the control of the nanoactivity and nanotoxicity of molecularly-capped or bio-conjugated nanoparticles. PMID- 26266625 TI - Mechanism of anisotropic surface self-diffusivity at the prismatic ice-vapor interface. AB - Predictive theoretical models for mesoscopic roughening of ice require improved understanding of attachment kinetics occurring at the ice-vapor interface. Here, we use classical molecular dynamics to explore the generality and mechanics of a transition from anisotropic to isotropic self-diffusivity on exposed prismatic surfaces. We find that self-diffusion parallel to the crystallographic a-axis is favored over the c-axis at sub-melt temperatures below about -35 degrees C, for three different representations of the water-water intermolecular potential. In the low-temperature anisotropic regime, diffusion results from interstitial admolecules encountering entropically distinct barriers to diffusion in the two in-plane directions. At higher temperatures, isotropic self-diffusion occurring deeper within the quasi-liquid layer becomes the dominant mechanism, owing to its larger energy of activation. PMID- 26266626 TI - John A. 'Jack' Smith, MD (Aug. 25, 1937-March 21, 2015). PMID- 26266628 TI - Strategies for Optimal MAC Parameters Tuning in IEEE 802.15.6 Wearable Wireless Sensor Networks. AB - Wireless body area networks (WBAN) has penetrated immensely in revolutionizing the classical heath-care system. Recently, number of WBAN applications has emerged which introduce potential limits to existing solutions. In particular, IEEE 802.15.6 standard has provided great flexibility, provisions and capabilities to deal emerging applications. In this paper, we investigate the application-specific throughput analysis by fine-tuning the physical (PHY) and medium access control (MAC) parameters of the IEEE 802.15.6 standard. Based on PHY characterizations in narrow band, at the MAC layer, carrier sense multiple access collision avoidance (CSMA/CA) and scheduled access protocols are extensively analyzed. It is concluded that, IEEE 802.15.6 standard can satisfy most of the WBANs applications throughput requirements by maximum achieving 680 Kbps. However, those emerging applications which require high quality audio or video transmissions, standard is not able to meet their constraints. Moreover, delay, energy efficiency and successful packet reception are considered as key performance metrics for comparing the MAC protocols. CSMA/CA protocol provides the best results to meet the delay constraints of medical and non-medical WBAN applications. Whereas, the scheduled access approach, performs very well both in energy efficiency and packet reception ratio. PMID- 26266629 TI - Discovery of gamma-MnP4 and the Polymorphism of Manganese Tetraphosphide. AB - A new polymorph of MnP4 was prepared by reaction of the elements via chemical vapor transport with iodine as transporting agent. The crystal structure was refined using single-crystal diffraction data (space group Cc, no. 9, a = 5.1049(8) A, b = 10.540(2) A, c = 10.875(2) A, beta = 93.80(2) degrees ). The phase is called gamma-MnP4 as it is isostructural with gamma-FeP4. It is the fourth reported binary polymorph in the MnP4 system, all of which are stacking variants of nets built with manganese and phosphorus atoms. In gamma-MnP4, there are two Mn-Mn distances (2.93 and 3.72 A) arising from a Peierls-like distortion effectively forming Mn2 dumbbells in the structure. Magnetic and electrical conductivity measurements show diamagnetism and a small anisotropic band gap (100 200 meV) with significantly enhanced conductivity along the crystallographic a axis. Calculations of the electronic and vibrational (phonon) structures show the P-P and Mn-P bonds within the nets are mainly responsible for the stability of the phase. The similar bonding motifs of the polymorphs give rise to the existence of numerous dynamically stable variants. The calculated Helmholtz energy shows the polymorph formation to be closely tied to temperature with the 6 MnP4 structure favorable at low temperatures, the 2-MnP4 favorable between approximately 800 and 2000 K, and 8-MnP4 preferred at high temperatures. PMID- 26266627 TI - Posttraumatic stress disorder and alcohol misuse among women: effects of ethnic minority stressors. AB - PURPOSE: The aims of this study were to examine the relationship between adult onset posttraumatic stress disorder (PTSD) and subsequent alcohol use outcomes (frequent heavy drinking, alcohol abuse, and alcohol dependence) in non-Hispanic white, non-Hispanic black, and Hispanic US women, and whether this relationship was moderated by ethnic minority stressors (discrimination and acculturation). METHODS: The study sample was drawn from two waves of the National Epidemiologic Surveys of Alcohol and Related Conditions, employing time-dependent data to conduct multiple extended Cox regression. RESULTS: Women with PTSD were over 50 % more likely than those without PTSD to develop alcohol dependence [adjusted hazards ratio (aHR) 1.55; 95 % confidence interval (CI) 1.15, 2.08]. Hispanic and black women were at lower risk of most alcohol outcomes than white women. In race /ethnic-specific analyses, however, PTSD only predicted alcohol abuse among Hispanic women (aHR 3.02; CI 1.33, 6.84). Higher acculturation was positively associated with all alcohol outcomes among Hispanic women and discrimination was associated with AUD among Hispanic and black women. Acculturation and discrimination modified the effect of PTSD on AUD among Hispanic women: PTSD predicted alcohol dependence among those with low acculturation (aHR 10.2; CI 1.27, 81.80) and alcohol abuse among those without reported discrimination (aHR 6.39; CI 2.76, 16.49). CONCLUSIONS: PTSD may influence the development of hazardous drinking, especially among Hispanic women. The influence of PTSD on alcohol outcomes is most apparent, however, when ethnic minority stressors are not present. PMID- 26266630 TI - Teneligliptin improves left ventricular diastolic function and endothelial function in patients with diabetes. AB - Incretin hormones have been reported to have cytoprotective actions in addition to their glucose-lowering effects. We evaluated whether teneligliptin, a novel dipeptidyl peptidase-4 (DPP-4) inhibitor, affects left ventricular (LV) function in patients with type 2 diabetes mellitus (T2DM). Twenty-nine T2DM patients not receiving any incretin-based drugs were enrolled and prescribed with teneligliptin for 3 months. Compared to baseline levels, hemoglobin A1c levels decreased (7.6 +/- 1.0 % to 6.9 +/- 0.7 %, p < 0.01) and 1,5-anhydro-D-glucitol levels increased (9.6 +/- 7.2 MUg/mL to 13.5 +/- 8.7 MUg/mL, p < 0.01) after treatment. Clinical parameters, including body mass index and blood pressure, did not show any difference before and after treatment. Three months after treatment, there were improvements in LV systolic and diastolic function [LV ejection fraction, 62.0 +/- 6.5 % to 64.5 +/- 5.0 %, p = 0.01; peak early diastolic velocity/basal septal diastolic velocity (E/e') ratio, 13.3 +/- 4.1 to 11.9 +/- 3.3, p = 0.01]. Moreover, there was an improvement in endothelial function (reactive hyperemia peripheral arterial tonometry [RH-PAT] index; 1.58 +/- 0.47 to 2.01 +/- 0.72, p < 0.01). There was a significant negative correlation between changes in the E/e' ratio and RH-PAT values. Furthermore, circulating adiponectin levels increased (27.0 +/- 38.5 pg/mL to 42.7 +/- 33.2 pg/mL, p < 0.01) without changes in patient body weight. Teneligliptin treatment was associated with improvements in LV function and endothelial functions, and an increase in serum adiponectin levels. These results support the cardio-protective effects of teneligliptin in T2DM patients and increase in serum adiponectin levels. PMID- 26266631 TI - Surgical management of left ventricular thrombus following severe dehydration. AB - We experienced a case involving a left ventricular ball-like thrombus caused by severe following a 150 mile cycling road race. The patient had lower-limb arterial obstruction due to systemic thromboembolism on admission with no significant embolism, including the cerebral arteries, were detected. Left ventricular wall motion was good with no evidence of left and right coronary artery occlusion; therefore, we performed emergency left ventricular thrombectomy. Although there are many reports of left ventricular thrombus following acute myocardial infarction, dehydration is a very rare cause. Herein, we describe the surgical and management approaches to the treatment of left ventricular thrombectomy in this case. PMID- 26266632 TI - Antiplatelet therapy in Takotsubo cardiomyopathy: does it improve cardiovascular outcomes during index event? AB - Plasma catecholamines may play an important role in Takotsubo cardiomyopathy (TCM) pathophysiology. Patients with disproportionately high catecholamine responses to stressful events are prone to worse clinical outcomes. Catecholamines stimulate platelet activation and, therefore, may determine the clinical presentation and outcomes of TCM. We conducted a retrospective, descriptive study TCM patients admitted between 2003 and 2013 to Einstein Medical Center, Philadelphia, PA, USA and Danbury Hospital, Danbury, CT, USA. A total of 206 patients met Modified Mayo TCM criteria. Using a multiple logistic model, we tested whether aspirin, dual antiplatelet therapy (DAPT) aspirin + clopidogrel, beta blocker, statin, or ACE inhibitor use were independent predictors of major adverse cardiovascular events (MACE) during the index hospitalization. MACE was defined as in-hospital heart failure, in-hospital death, stroke or respiratory failure requiring mechanical ventilation. Incidence of in-hospital heart failure was 26.7 %, in-hospital death was 7.3 %, stroke was 7.3 % and MACE was 42.3 %. In a multiple logistic regression model (adjusted for gender, race, age, physical stressor, hypertension, diabetes, hyperlipidemia, smoking history, body mass index, initial left ventricular ejection fraction, single antiplatelet therapy, DAPT, beta blocker, statin, and ACE inhibitor) aspirin and DAPT at the time of hospitalization were independent predictors of a lower incidence of MACE during the index hospitalization (aspirin: OR 0.4, 95 % CI (0.16-0.9), P = 0.04; DAPT: OR 0.23; 95 % CI (0.1-0.55); P < 0.01. Physical stressor itself was also found to be an independent predictor of worse MACE: OR 5.1; 95 % CI (2.4-11.5); P < 0.01. In our study, aspirin and DAPT were independent predictors of a lower incidence of MACE during hospitalization for TCM. Prospective clinical trials are needed to confirm the findings of this study. PMID- 26266633 TI - Prevalence, implication, and determinants of worsening renal function after surgery for congenital heart disease. AB - Accumulating data in adults indicate the prognostic importance of worsening renal function (WRF) during treatment of acute heart failure. Venous congestion appears to play a dominant role in WRF; however, data regarding WRF in children with congenital heart disease (CHD) are limited. The present study was conducted to elucidate the prevalence and characteristics of WRF after surgery for CHD in children. We also tested our hypothesis that, similar to adult heart failure, venous congestion is an important determinant of WRF independent of cardiac output in this population. Fifty-five consecutive pediatric patients who underwent cardiovascular surgery for CHD were studied (median age 0.7 years; range 3 days to 17 years). The degree of WRF was assessed by the difference between the maximum levels of postoperative serum creatinine (Cr) and preoperative serum Cr. There was a high prevalence of WRF in the present cohort: an increase in Cr level was observed in 47 patients (85 %) and a Cr increase >=0.3 mg/dL was seen in 23 (42 %). Importantly, WRF was significantly associated with a worse clinical outcome of a longer stay in the intensive care unit and hospital (both p < 0.05), even after controlling for age and operative factors. In addition, multivariate regression analysis revealed that central venous pressure, rather than cardiac output, was an independent determinant of WRF. Postoperative management to relieve venous congestion may help ameliorate or prevent WRF and thereby improve outcomes in patients with CHD. PMID- 26266634 TI - Comparison of clinical characteristics in patients with Takayasu arteritis with and without concomitant tuberculosis. AB - Because of frequent tuberculosis in patients with Takayasu arteritis (TA), a possible relationship between TA and tuberculosis has been proposed. However, there are no studies to date that have examined clinical manifestations in patients diagnosed with TA with or without tuberculosis. Two hundred sixty-seven patients were diagnosed with TA according to the 1990 American College of Rheumatology criteria between September 1994 and April 2014. Patients with TA were classified into groups with or without tuberculosis. Among the 267 patients with TA studied, 47 patients (17.7 %) who had a history of previous treatment of tuberculosis (34 patients), concurrent diagnosis of tuberculosis with TA (10 patients), or diagnosis of tuberculosis during the follow-up period for TA (3 patients) were included in the group with tuberculosis. The group with tuberculosis comprised of 33 patients (70.2 %) with pulmonary tuberculosis, 12 patients (25.5 %) with tuberculous lymphadenitis, and 2 patients (4.3 %) with tuberculosis of the skin and colon, respectively. Comorbid disease and patients' signs and symptoms were not significantly different between TA patients with and without tuberculosis. Additionally, the site of disease involvement in angiographic findings and distribution of angiographic type were similar between the two groups. In conclusion, tuberculosis including tuberculous lymphadenitis was frequently observed in patients with TA. Clinical features and angiographic findings in TA were not different according to the presence or absence of concomitant tuberculosis. PMID- 26266635 TI - Larger low voltage zone in endocardial unipolar map compared with that in epicardial bipolar map indicates difficulty in eliminating ventricular tachycardia by catheter ablation. AB - Patients with ischemic and non-ischemic cardiomyopathy often have substrate for ventricular tachycardia (VT) in the endocardium (ENDO), epicardium (EPI), and/or intramural. Although it has been reported that the ENDO unipolar (UNI) voltage map is useful in detecting EPI substrate, its feasibility to detect intramural scarring and its usefulness in radiofrequency catheter ablation (RFCA) remain unclear. To assess the relationship between the left ventricle (LV) ENDO UNI voltage map and the LV EPI bipolar (BIP) voltage map, and to determine the usefulness of the ENDO UNI voltage map to guide RFCA for VT in patients with cardiomyopathy undergoing combined ENDO- and EPI RFCA. Eleven patients with VT undergoing detailed ENDO and EPI electroanatomical mapping of the LV were included (mean age 59 +/- 11 years, 9 men). We assessed the value of the LV ENDO UNI voltage map in identifying EPI and/or intramural substrate in these 11 patients with non-ischemic or ischemic cardiomyopathy. The underlying heart disease was dilated cardiomyopathy in 4 patients, cardiac sarcoidosis in 3, hypertrophic cardiomyopathy in 2, and ischemic heart disease in 2 patients. The mean LV ejection fraction was 24 +/- 7 %. The low voltage zone (LVZ) was defined as <1.5 mV for LV ENDO BIP electrograms (EGMs), <8.3 mV for LV ENDO UNI EGMs, and <1.0 mV for LV EPI BIP EGMs. The surface area of each LVZ was measured. We also measured the LVZ of the spatial overlap between ENDO UNI and EPI BIP voltage maps using the transparency mode on CARTO software. We performed RFCA at the ENDO and EPI based on activation and/or substrate maps, targeting the LVZ and/or abnormal EGMs. The LVZ was present in the LV ENDO BIP voltage map in 10 of 11 patients (42 +/- 33 cm(2)), and in the LV ENDO UNI voltage map in 10 of 11 patients (72 +/- 45 cm(2)). The LVZ was present in the EPI BIP voltage map in 9 of 11 patients (70 +/ 61 cm(2)), and the LVZ in the ENDO UNI voltage map was also seen in all 9 patients. The location of the LVZ in the EPI BIP map matched that in 45 +/- 28 % of ENDO UNI voltage maps. The LVZ in the ENDO UNI voltage map was larger than that in the EPI BIP voltage map in 6 of 11 patients, and RFCA failed in 5 of these 6 patients. In the remaining 5 patients with a smaller LVZ in the ENDO UNI voltage map compared with the EPI BIP voltage map or no LVZ both at ENDO UNI and EPI BIP voltage map, VT was successfully eliminated in 4 of 5 patients. The LV ENDO UNI voltage map is useful in detecting EPI substrate in patients with cardiomyopathy. A larger LVZ in the ENDO UNI voltage map compared to that in the EPI BIP voltage map may indicate the presence of intramural substrate, which leads to difficulty in eliminating VT, even with combined ENDO- and EPI RFCA. PMID- 26266636 TI - Towards high throughput screening of electrochemical stability of battery electrolytes. AB - High throughput screening of solvents and additives with potential applications in lithium batteries is reported. The initial test set is limited to carbonate and phosphate-based compounds and focused on their electrochemical properties. Solvent stability towards first and second reduction and oxidation is reported from density functional theory (DFT) calculations performed on isolated solvents surrounded by implicit solvent. The reorganization energy is estimated from the difference between vertical and adiabatic redox energies and found to be especially important for the accurate prediction of reduction stability. A majority of tested compounds had the second reduction potential higher than the first reduction potential indicating that the second reduction reaction might play an important role in the passivation layer formation. Similarly, the second oxidation potential was smaller for a significant subset of tested molecules than the first oxidation potential. A number of potential sources of errors introduced during screening of the electrolyte electrochemical properties were examined. The formation of lithium fluoride during reduction of semifluorinated solvents such as fluoroethylene carbonate and the H-transfer during oxidation of solvents were found to shift the electrochemical potential by 1.5-2 V and could shrink the electrochemical stability window by as much as 3.5 V when such reactions are included in the screening procedure. The initial oxidation reaction of ethylene carbonate and dimethyl carbonate at the surface of the completely de-lithiated LiNi0.5Mn1.5O4 high voltage spinel cathode was examined using DFT. Depending on the molecular orientation at the cathode surface, a carbonate molecule either exhibited deprotonation or was found bound to the transition metal via its carbonyl oxygen. PMID- 26266637 TI - Targeted Therapy in Biliary Tract Cancers. AB - OPINION STATEMENT: A paradigm shift towards molecular-based, personalized cancer therapeutics has occurred in recent years and a number of targeted drugs have emerged. Various targeted therapies like erlotinib, trastuzumab, and cetuximab have been approved in lung, breast, and colon cancers, respectively. Numerous clinical trials involving targeted drugs in biliary tract cancers are currently in progress, though none have been approved for this disease. Biliary tract cancers are divided into separate entities both anatomically and in terms of pathogenesis but are grouped together in most trials given their rarity. Combination chemotherapy involving cisplatin and gemcitabine is the current standard of care in the metastatic setting. In this review, we will discuss the various molecular pathways implicated in biliary tract cancers and potential therapeutic targets. PMID- 26266638 TI - Factors governing the immunosuppressive effects of multipotent mesenchymal stromal cells in vitro. AB - Multipotent mesenchymal stem/stromal cells (MSCs) are of great interest to researchers because of the unique properties, such as enhanced proliferation, paracrine activity and multilineage differentiation. Their non-immunogenicity, in combination with immunomodulatory properties, opens up the opportunity for the allogeneic application of MSCs. The MSC immunomodulatory capacity is currently being actively studied in vitro using various experimental designs. However, the results are not always univocal. It was found that the outcome of the stromal/immune cell interaction depends on experimental conditions. In this review we considered the impact of different factors, such as the ratio of stromal/immune cells, interaction time, the path of immune cell activation, etc. on the MSC immunomodulation. We also accentuated the importance of local milieu, in particular, oxygen tension, for the realization of MSC immunosuppressive activity. PMID- 26266639 TI - Current status of local treatment for early rectal cancer in Japan: a questionnaire survey by the 81st Congress of the Japanese Society for Cancer of the Colon and Rectum (JSCCR) in 2014. AB - PURPOSE: The aim of this questionnaire survey was to assess the change in treatment modality over time and the current status of clinical outcomes of local treatment in Japanese patients with pathological T1 (pT1) rectal tumors. METHODS: A questionnaire survey was conducted by the 81st Congress of the Japan Society for Cancer of the Colon and Rectum. Clinical and pathological outcomes of all eligible patients undergoing local treatment were retrospectively collected from the medical records of each participating hospital. RESULTS: A total of 1371 pT1 patients from January 2006 to December 2008 (Period A), and 659 patients in 2013 (Period B) were registered. Approximately 70 % of patients underwent radical surgery in both periods. The rate of patients undergoing laparoscopic surgery increased from 46.5 % in Period A to 84.7 % in Period B. The indications for local excision were comparable with those for endoscopic intervention in 78 % of institutions. The rate of endoscopic submucosal dissection (ESD) increased from 20.1 % in Period A to 37.9 % in Period B, whereas local excision decreased from 36.9 to 24.1 %. Few patients received adjuvant therapy, and approximately 40 % of patients underwent additional surgery in both periods. Local recurrence was observed in 9.2 % of patients in Period A, with the median follow-up period being 59 months. Eighty-two percent of patients with local recurrence underwent salvage surgery. CONCLUSIONS: Local treatment with various modalities was properly performed for early rectal cancer. The number of less invasive modalities, such as laparoscopic surgery and ESD, increased between study periods. PMID- 26266641 TI - Erratum to: Gender differences in colorectal cancer survival in Japan. PMID- 26266640 TI - Phase I dose escalation study of amrubicin plus paclitaxel in previously treated advanced non-small cell lung cancer. AB - BACKGROUND: We conducted a phase I dose escalation study to determine the maximum tolerated dose (MTD), the recommended dose (RD) and the safety profile of amrubicin (AMR) plus paclitaxel (PTX) combination regimen for patients with previously treated non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: PTX was administered at a fixed dose of 150 mg/m(2)/day on day 1 and AMR was intravenously administered at a starting dose of 25 mg/m(2)/day on days 1-3, and this was repeated every 4 weeks. Doses of each drug were planned as follows-level 0, 20/150; level 1, 25/150; level 2, 30/150; level 3, 30/180 AMR mg/m(2) per day/PTX mg/m(2) per day. RESULTS: Twelve patients were enrolled in this study. The dose-limiting toxicity (DLT) of the regimen was assessed during the first cycle. At level 1, all three patients developed a DLT due to grade 4 neutropenia lasting >4 days, grade 4 thrombocytopenia and grade 3 febrile neutropenia. Therefore, level 1 was considered the MTD and level 0 was selected as the RD. Objective responses were seen in two patients (response rate 16.7 %). Overall disease control rate was 91.7 %. CONCLUSIONS: The combination of AMR and PTX is a feasible and well-tolerated regimen for the treatment of patients with previously treated advanced NSCLC. Although our study included a small number of patients, encouraging disease control and progression-free survival were achieved at the recommended doses. Further clinical trials are warranted. PMID- 26266642 TI - Relationship between quality of life instruments and phonatory function in tracheoesophageal speech with voice prosthesis. AB - BACKGROUND: The use of tracheoesophageal speech with voice prosthesis (T-E speech) after total laryngectomy has increased recently as a method of vocalization following laryngeal cancer. Previous research has not investigated the relationship between quality of life (QOL) and phonatory function in those using T-E speech. This study aimed to demonstrate the relationship between phonatory function and both comprehensive health-related QOL and QOL related to speech in people using T-E speech. METHODS: The subjects of the study were 20 male patients using T-E speech after total laryngectomy. At a visit to our clinic, the subjects underwent a phonatory function test and completed three questionnaires: the MOS 8-Item Short-Form Health Survey (SF-8), the Voice Handicap Index-10 (VHI-10), and the Voice-Related Quality of Life (V-RQOL) Measure. RESULTS: A significant correlation was observed between the physical component summary (PCS), a summary score of SF-8, and VHI-10. Additionally, a significant correlation was observed between the SF-8 mental component summary (MCS) and both VHI-10 and VRQOL. Significant correlations were also observed between voice intensity in the phonatory function test and both VHI-10 and V RQOL. Finally, voice intensity was significantly correlated with the SF-8 PCS. CONCLUSIONS: QOL questionnaires and phonatory function tests showed that, in people using T-E speech after total laryngectomy, voice intensity was correlated with comprehensive QOL, including physical and mental health. This finding suggests that voice intensity can be used as a performance index for speech rehabilitation. PMID- 26266643 TI - Electron Capture Dissociation of Sodium-Adducted Peptides on a Modified Quadrupole/Time-of-Flight Mass Spectrometer. AB - Electron capture dissociation (ECD), which generally preserves the position of labile post-translational modifications, can be a powerful method for de novo sequencing of proteins and peptides. In this report, ECD product-ion mass spectra of singly and doubly sodiated, nonphosphorylated, and phosphorylated peptides are presented and compared with the ECD mass spectra of their protonated counterparts. ECD of doubly charged, singly sodiated peptides yielded essentially the same sequence information as was produced by the corresponding doubly protonated peptides. The presence of several sodium binding sites on the polypeptide backbone, however, resulted in more complicated spectra. This situation is aggravated by the zwitterionic equilibrium of the free acid peptide precursors. The product-ion spectra of doubly and triply charged peptides possessing two sodium ions were further complicated by the existence of isomers created by the differential distribution of sodium binding sites. Triply charged, phosphorylated precursors containing one sodium, wherein the sodium is attached exclusively to the PO4 group, were found to be as useful for sequence analysis as the fully protonated species. Although sodium adducts are generally minimized during sample preparation, it appears that they can nonetheless provide useful sequence information. Additionally, they enable straightforward identification of a peptide's charge state, even on low-resolution instruments. The experiments were carried out using a radio frequency-free electromagnetostatic cell retrofitted into the collision-induced dissociation (CID) section of a hybrid quadrupole/time-of-flight tandem mass spectrometer. Graphical Abstract ?. PMID- 26266645 TI - Treatment of Enamel Surfaces After Bracket Debonding: Case Reports and Long-term Follow-ups. AB - After bracket debonding, residual bonded material may be observed on the enamel surface. When not properly removed, this residual material can interfere with the surface smoothness of the enamel, potentially resulting in staining at the resin/enamel interface and contributing to biofilm accumulation. Clinical case reports demonstrate clinical procedures to remove residual bonded material after bracket debonding. A water-cooled fine tapered 3195 FF diamond bur was used to remove the residual bonded material. Subsequently, the enamel surface was treated with Opalustre microabrasive compound. After one week, overnight dental bleaching was initiated using 10% carbamide peroxide in custom-formed trays for four weeks. The enamel microabrasion technique was found to be effective for polishing the enamel surface and for reestablishing the dental esthetics associated with dental bleaching. Longitudinal clinical controls of other clinical cases are presented. PMID- 26266646 TI - Effect of High-Fluoride Dentifrice on Enamel Erosion Adjacent to Restorations In Vitro. AB - AIM: This in vitro study analyzed the antierosive potential of a high-fluoride dentifrice on enamel adjacent to restorations. METHODS AND MATERIALS: Enamel blocks (6 * 6 * 3 mm) from bovine incisor teeth were restored with three different restorative materials (resin, conventional glass ionomer cement, and resin-modified glass ionomer cement) and treated with dentifrices containing 0, 1100, or 5000 ppm F. After restorative procedures, initial surface Vickers hardness of the blocks were obtained. The specimens were submitted to pH cycles (4 * 90 seconds in soft drink) and treatments for five days. Between the challenges and overnight, the blocks remained in artificial saliva. At the end of the experiment, the final hardness was assessed and the percentage of surface mineral loss (%SML) was calculated. A 3 * 3 factorial design was used to conduct statistical analysis. Data were analyzed by analysis of variance and t-test, with significance level fixed at 5%. RESULTS: High-fluoride dentifrice decreased demineralization caused by erosive challenge regardless of the restorative material used (p<0.001). Likewise, the blocks restored with conventional glass ionomer cement showed lower values of SML irrespective of dentifrice used (p<0.001). CONCLUSION: Use of a high-fluoride dentifrice on teeth restored with conventional glass ionomer cement offers additional protection against enamel erosion. PMID- 26266647 TI - Influence of Adhesive Core Buildup Designs on the Resistance of Endodontically Treated Molars Restored With Lithium Disilicate CAD/CAM Crowns. AB - OBJECTIVE: To assess the influence of adhesive core buildup designs (4-mm buildup, 2-mm buildup, and no buildup/endocrown) on the fatigue resistance and failure mode of endodontically treated molar teeth restored with lithium disilicate computer-aided design/computer-aided manufacturing (CAD/CAM) complete crowns placed with self-adhesive cement. METHODS AND MATERIALS: Forty-five extracted molars were decoronated at the level of the cementoenamel junction and endodontically treated. Specimens received different Filtek Z100 adhesive core buildups (4-mm buildup; 2-mm buildup; and no buildup endocrown preparation) and were restored with Cerec 3 CAD/CAM lithium disilicate crowns (IPS e.max CAD). The intaglio surfaces of restorations (n=15) were conditioned by hydrofluoric acid etching and silane, and prepared teeth were treated with airborne-particle abrasion, followed by cementation with RelyX Unicem 2 Automix. Specimens were then subjected to cyclic isometric loading at 10 Hz, beginning with a load of 200 N (*5000 cycles), followed by stages of 400, 600, 800, 1000, 1200, and 1400 N at a maximum of 30,000 cycles each. Specimens were loaded until failure or to a maximum of 185,000 cycles. The chewing cycle was simulated by an isometric contraction (load control) applied through a 10-mm in diameter composite resin sphere (Filtek Z100). Surviving specimens were axially loaded until failure or to a maximum load of 4500 N (crosshead speed 0.5 mm/min). The failure mode was assessed, and fractures were designated as catastrophic (tooth/root fracture that would require tooth extraction) or reparable (cohesive or cohesive/adhesive fracture of restoration only). Groups were compared using the life table survival analysis (log-rank test at p=0.05). Surviving specimens were loaded to failure and compared with one-way analysis of variance. RESULTS: The survival rates after the fatigue test were 100%, 93%, and 100% for 4-mm, 2-mm, and no buildup (endocrown), respectively and were not statistically different (only one specimen failed with a 2-mm buildup under a crown that cohesively fractured at 1,400 N). Postfatigue load to failure averaged 3181 N for 4-mm buildups (15 specimens), 3759 N for 2-mm buildups (12 specimens), and 3265 N for endocrowns (14 specimens). The 2-mm buildups were associated with higher loads to failure than endocrowns and 4-mm buildups, but no differences were found between 4-mm buildups and endocrowns (p<0.05.) One endocrown and 2 restorations with a 2-mm buildup survived the load-to-failure test (at 4500 N). Only catastrophic fractures occurred after the load-to-failure test. CONCLUSIONS: The buildup design influenced the performance of endodontically treated molars restored with lithium disilicate CAD/CAM complete crowns placed with self-adhesive resin cement. The 2 mm buildups were associated with higher loads to failure than the endocrown and the 4-mm buildup, but all restoration designs survived far beyond the normal range of masticatory forces. PMID- 26266648 TI - CAD/CAM Polymer vs Direct Composite Resin Core Buildups for Endodontically Treated Molars Without Ferrule. AB - OBJECTIVES: The aim of this study was to investigate the restoration of broken down endodontically treated molars without ferrule effect using glass ceramic crowns on different composite resin core buildups. METHODS AND MATERIALS: Forty five decoronated endodontically treated teeth (no ferrule) were restored with a semidirect buildup using an experimental computer-aided design/computer-aided manufacturing (CAD/CAM) high-performance polymer (HPP group) or with light-curing composite core buildups of Tetric EvoCeram with (TECP group) or without (TEC group) a glass-fiber-reinforced post. All teeth were prepared to receive bonded glass ceramic crowns (Empress CAD luted with Variolink II) and were subjected to accelerated fatigue testing. Cyclic isometric loading was applied to the palatal cusp at an angle of 30 degrees and a frequency of 5 Hz, beginning with a load of 200 N (*5000 cycles) and followed by stages of 400, 600, 800, 1000, 1200, and 1400 N at a maximum of 30,000 cycles each. Specimens were loaded until failure or to a maximum of 185,000 cycles. Groups were compared using the life-table survival analysis (log rank test at p=0.05). Average fracture loads and number of survived cycles were compared with one-way analysis of variance (Scheffe post hoc at p=0.05). RESULTS: None of the tested specimen withstood all 185,000 load cycles. There was a significant difference in mean fracture load, survived cycles, and survival; the HPP group (fracture load 975.27N+/-182.74) was significantly higher than the TEC (716.87N+/-133.43; p=0.001) and TECP (745.67+/ 156.34; p=0.001) groups, and the TEC and TECP groups showed no difference (p=0.884). Specimens in the TECP group were affected by an initial failure phenomenon (wide gap at the margin between the buildup/crown assembly and the root). CONCLUSIONS: Semidirect core buildup made from high-performance polymer enhanced the performance of all-ceramic leucite-reinforced glass ceramic crowns compared with direct light-curing composite resin buildups. The use of a fiber reinforced post system did not influence the fatigue strength of all-ceramic crowns. PMID- 26266649 TI - Effect of Bleaching Agents on the Nanohardness of Tooth Enamel, Composite Resin, and the Tooth-Restoration Interface. AB - This in vitro study aimed to evaluate the nanohardness of tooth enamel, composite resin, dental adhesive, and enamel hybrid layer exposed to 35% hydrogen peroxide based bleaching agents and analyze the tooth-restoration interface using scanning electron microscopy (SEM). This study used 40 crowns of bovine incisors, which were embedded in epoxy resin. A 2 * 2 * 2-mm cavity was prepared in the medial third of the flattened buccal surface of each tooth and restored (two-step etch and-rinse Adper Single Bond 2 + nanocomposite resin Filtek Z350 XT). The specimens were polished and divided into four groups (n=10), corresponding to each bleaching agent used (TB: Total Blanc Office, pH=7.22-6.33; HPB: Whiteness HP Blue, pH=8.89-8.85; HP: Whiteness HP, pH=6.65-6.04; PO: Pola Office, pH=3.56 3.8), applied in accordance with manufacturer protocols. The nanohardness of the substrates was measured before and immediately after the bleaching procedure and after 7-day storage in artificial saliva with an Ultra-Microhardness Tester (DUH 211S, Shimadzu). Loads used were 100 mN for tooth enamel and composite resin and 10 mN for adhesive and enamel hybrid layer. For SEM analysis, epoxy replicas were prepared through high-precision impressions of the specimens. For nanohardness, the statistical tests two-way analysis of variance and Tukey (p<0.05) revealed that the agent with the lowest pH value (PO) was the only one to decrease the nanohardness of enamel and the enamel hybrid layer immediately after its application; however, after 7-day storage in artificial saliva, the nanohardness levels of these substrates returned to their original values. SEM analysis revealed small gaps between tooth enamel and adhesive after the exposure to all bleaching agents; however, the most evident gap in the tooth-restoration interface was observed immediately after application of agent PO. No bleaching agent used changed the nanohardness of the composite resin and adhesive layer. PMID- 26266644 TI - How Does p73 Cause Neuronal Defects? AB - The p53-family member, p73, plays a key role in the development of the central nervous system (CNS), in senescence, and in tumor formation. The role of p73 in neuronal differentiation is complex and involves several downstream pathways. Indeed, in the last few years, we have learnt that TAp73 directly or indirectly regulates several genes involved in neural biology. In particular, TAp73 is involved in the maintenance of neural stem/progenitor cell self-renewal and differentiation throughout the regulation of SOX-2, Hey-2, TRIM32 and Notch. In addition, TAp73 is also implicated in the regulation of the differentiation and function of postmitotic neurons by regulating the expression of p75NTR and GLS2 (glutamine metabolism). Further still, the regulation of miR-34a by TAp73 indicates that microRNAs can also participate in this multifunctional role of p73 in adult brain physiology. However, contradictory results still exist in the relationship between p73 and brain disorders, and this remains an important area for further investigation. PMID- 26266650 TI - Effect of Different Light Sources and Enamel Preconditioning on Color Change, H2O2 Penetration, and Cytotoxicity in Bleached Teeth. AB - This study evaluated the effects of acid etching of the enamel and the combination of different light sources (halogen light, light-emitting diodes [LEDs], and LED/Laser) and the bleaching product on color change, penetration of hydrogen peroxide (H2O2), and cytotoxicity over time. The color change (DeltaE) and the amount of H2O2 that permeated the tooth tissue were analyzed using a spectrophotometer. Cell metabolism and morphology were evaluated using the methylthiazol tetrazolium assay and scanning electron microscopy, respectively. The DeltaE values and H2O2 permeation were not significantly different under any of the experimental conditions. Tooth whitening significantly reduced cell metabolism, regardless of whether a light source was used. Preconditioning the enamel did not influence the cellular metabolism in any group. In conclusion, combining the bleaching product with different light sources and/or preconditioning the enamel resulted in few significant changes in color, transenamel and transdentinal penetration of H2O2, or cytotoxicity and cell morphology. PMID- 26266651 TI - Effect of Restorative System and Thermal Cycling on the Tooth-Restoration Interface - OCT Evaluation. AB - The present study evaluated the tooth/noncarious cervical lesion restoration interface when using different adhesive systems and resin composites, submitted to thermal cycling (TC), using optical coherence tomography (OCT). Noncarious cervical lesion (NCCL) preparations (0.7 mm depth * 2 mm diameter) were performed on 60 human third molars and randomly divided into six groups, according to the adhesive system and resin composite used: group 1 = Adper Single Bond 2 (SB2) + Aelite LS Posterior (AP); group 2 = SB2 + Venus Diamond (VD); group = SB2 + Filtek Z250XT (Z250); group 4 = Clearfil SE Bond (CSE) + AP; group 5 = CSE + VD; group 6 = CSE + Z250. Selective enamel etching was performed for 30 seconds on groups 4, 5, and 6, while groups 1, 2, and 3 were etched for 30 seconds in enamel and 15 seconds in dentin. All groups were evaluated using OCT before and after TC (n=10). Images were analyzed using Image J software; enamel and dentin margins were separately evaluated. Data from OCT were submitted to PROC MIXED for repeated measurements and Tukey Kramer test (alpha = 0.05). No marginal gaps were observed in etched enamel, either before or after TC, for all adhesive and resin composite systems. A significant interaction was found between adhesive system and TC for the dentin groups; after TC, restorations with CSE showed smaller gaps at the dentin/restoration interface compared with SB2 for all resin composites. Increased gap percentages were noticed after TC compared with the gaps before TC for all groups. In conclusion, TC affected marginal integrity only in dentin margins, whereas etched enamel margins remained stable even after TC. Dentin margins restored with CSE adhesive system showed better marginal adaptation than those restored with SB2. Resin composites did not influence marginal integrity of NCCL restorations. PMID- 26266652 TI - Resin Bonding to a Hybrid Ceramic: Effects of Surface Treatments and Aging. AB - The aim of this study was to verify the effects of different surface treatments on the microtensile bond strength between resin cement and a hybrid ceramic. Thirty-two hybrid ceramic slices (8 * 10 * 3 mm) were produced and allocated among four groups according to the surface treatment: Cont = no treatment, HA = 10% hydrofluoric acid applied for 60 seconds, PA = 37% phosphoric acid applied for 60 seconds and CJ = air abrasion with silica particle coated alumina (Cojet Sand, 3M ESPE, 30 MUm/2.8 bar). As a control group, eight blocks of feldspathic ceramic (8 * 10 * 3 mm) were etched by hydrofluoric acid for 60 seconds (VMII). After the surface treatments, the ceramic slices were silanized (except the Cont group) and adhesively cemented to composite resin blocks (8 * 10 * 3 mm ) with a load of 750 g (polymerized for 40 seconds each side). The cemented blocks were cut into beams (bonded surface area of ~1 mm(2)). Half of the beams were aged (thermocycling of 5 degrees C-55 degrees C/6000 cycles + water storage at 37 degrees C/60 days), and the other half were tested immediately after being cut. Data were analyzed by Kruskal-Wallis and Dunn tests (non-aged groups) and by one way analysis of variance and Tukey test (aged groups; alpha=0.05%). The mode of failure was classified by stereomicroscopy. The surface treatment significantly affected the bond strength in each set of groups: non-aged (p=0.001) and aged (p=0.001). Before being aged, samples in the CJ, HA, and PA groups achieved the highest bond strength values. However, after being aged, only those in the HA group remained with the highest bond strength values. Adhesive failure was found most often. In conclusion, hydrofluoric acid etching should be used for surface conditioning of the studied hybrid ceramic. PMID- 26266653 TI - Marginal Integrity of Bulk Versus Incremental Fill Class II Composite Restorations. AB - Bulk-fill composites have been introduced to facilitate the placement of deep direct resin composite restorations. This study aimed at analyzing the cervical marginal integrity of bulk-fill vs incremental and open-sandwich class II resin composite restorations after thermomechanical cycling using replica scanning electron microscopy (SEM) and ranking according to the World Dental Federation (FDI) criteria. Box-only class II cavities were prepared in 91 maxillary premolars with the gingival margin placed 1 mm above and below the cemento-enamel junction. Eighty-four premolars were divided into self-etch and total-etch groups, then subdivided into six restorative subgroups (n=7): 1-Tetric Ceram HB (TC) was used incrementally and in the open-sandwich technique with 2-Tetric EvoFlow (EF) and 3-Smart Dentin Replacement (SD). Bulk-fill restoratives were 4 SonicFill (SF), 5-Tetric N-Ceram Bulk Fill (TN), and 6-Tetric EvoCeram Bulk Fill (TE). In subgroups 1-5, Tetric N-Bond self-etch and Tetric N-Bond total-etch adhesives were used, whereas in subgroup 6, AdheSE self-etch and ExciTE F total etch were used. One more group (n=7) was restored with Filtek P90 Low Shrink Posterior Restorative (P9) only in combination with its self-etch P90 System Adhesive. Materials were manipulated and light cured (20 seconds, 1600 mW/cm(2)), and restorations were artificially aged by thermo-occlusal load cycling. Polyvinyl-siloxane impressions were taken and poured with epoxy resin. Resin replicas were examined by SEM (200*) for marginal sealing, and percentages of perfect margins were analyzed. Moreover, samples were examined using loupes (3.5*) and explorers and categorized according to the FDI criteria. Results were statistically analyzed (SEM by Kruskal-Wallis test and FDI by chi-square test) without significant differences in either the replica SEM groups (p=0.848) or the FDI criteria groups (p>0.05). The best SEM results at the enamel margin were in TC+EF/total-etch and SF/total-etch and at the cementum margins were in SF/total etch and TE/self-etch, while the worst were in TC/self-etch at both margins. According to FDI criteria, the best was TE/total-etch at the enamel margin, and the poorest was P9/self-etch at the cementum margin. Groups did not differ significantly, and there was a strong correlation in results between replica SEM and FDI ranking. PMID- 26266654 TI - Influence of Light-curing Parameters on Biofilm Development and Flexural Strength of a Silorane-based Composite. AB - OBJECTIVES: The aim of this study was to evaluate the differences in biological and mechanical performances of a silorane-based and a methacrylate-based composite. Another aim was to assess the influence of light-curing time and light curing intensity on in vitro biofilm formation and flexural strength of the two tested composites. METHODS: Experiment 1: 432 specimens obtained from a silorane based composite and from a standard methacrylate-based composite were divided into six groups and light-cured for 10, 20, 30, 40, 60, or 80 seconds, using one of two light-curing intensities, 400 mW/cm(2) or 800 mW/cm(2). At 24 hours, a monospecific Streptococcus mutans biofilm adherent to the surfaces of the samples was obtained. Then, a colorimetric technique (MTT assay) was used to evaluate the adherent viable biomass. Two samples per group were observed using confocal laser scanning microscopy. Analysis of variance (ANOVA) and Tukey tests were used to analyze the results (p<0.05). Experiment 2: 192 bar-shaped specimens were obtained and light-cured as in the previous experiment. A three-point bend test using a universal testing machine was performed to obtain flexural strength values. ANOVA and Tukey tests were used to analyze the results (p<0.05). RESULTS: In experiment 1, a highly significant difference (p<0.0001) in biofilm development was shown between silorane-based and methacrylate-based composites. In fact, the silorane-based composite exhibited better biological performance. Significant differences were also found between the two light-curing intensities (p<0.018) and for curing times (p<0.0001): silorane-based composite light-cured for 80 seconds at 800 mW/cm(2) light-curing intensity showed the lowest biofilm development. In experiment 2, a significant difference in flexural strength (p<0.0318) was only found between the different composites. Nevertheless, both resin composites showed flexural strength values in accordance with International Organization for Standardization guidelines even after 10 seconds of light-curing time. CONCLUSIONS: Silorane-based composite was less prone to biofilm development compared with a methacrylate-based composite. Acceptable flexural strength values for both composites were obtained after 10 seconds of light-curing time. PMID- 26266655 TI - Fatigue Resistance of Y-TZP/Porcelain Crowns is Not Influenced by the Conditioning of the Intaglio Surface. AB - OBJECTIVES: The objective of this study was to investigate the effects of treatments of the intaglio surface of Y-TZP frameworks and luting agents on the fatigue resistance of all-ceramic crowns. METHODS: A research design was chosen that attempted to reduce the likelihood of Hertzian cracking and to increase the probability of fracture initiation at the intaglio surface of the framework. Ninety identical preparations were machined in a dentin-like epoxy composite. Each preparation was restored with a Y-TZP framework made by a CAD/CAM system and veneered using feldspathic ceramic. Prior to cementation the intaglio surface of the ceramic was treated using one of four treatments: 1) cleaning with isopropyl alcohol; 2) application of an overglaze; 3) sandblasting with 125 MUm aluminum oxide powder; and 4) sandblasting with 30 MUm silica powder (CJ). One of three luting cements were used: 1) zinc phosphate; 2) glass ionomer; and 3) adhesive resin cement (PN). All three cements were tested against frameworks that were alcohol cleaned. Only the PN cements were tested against frameworks that had been sandblasted or glazed. Altogether, six groups of 15 specimens each were tested. Fatigue resistance was evaluated using stepwise loads at 1.4 Hz until failure: 5000 cycles at maximum load of 200 N, followed by 10,000 cycles at maximum loads of 800, 1000, 1200, and 1400 N. The cement thickness and failure modes were analyzed using a stereomicroscope and scanning electron microscopy. The results were analyzed using the Kaplan-Meier and Mantel-Cox log rank tests (5%), a one way analysis of variance, Tukey multiple comparison test, and Weibull nonparametric test. RESULTS: The predominant failure mode was chipping of the veneer. The crowns cemented with the adhesive resin cement exhibited chipping failure at higher mean loads than did crowns cemented with cements that usually do not bond strongly with dentin. When the adhesive cement was used, glazing and sandblasting intaglio framework surface treatments exhibited lower mean loads at chipping than did crowns whose intaglio surface was only cleaned with alcohol. Weibull analysis indicated that all specimens had a high ratio of late-to-early failures. CONCLUSIONS: The fatigue experiment produced a pattern of failures that is very similar to that observed in clinical trials of Y-TZP crowns that are veneered with feldspathic porcelain. Crowns cemented with an adhesive resin cement exhibited chipping at a significantly higher mean load than those cemented with luting cements that do not usually form strong bonds with dentin. When cemented with adhesive resin cement, glazing or sandblasting the intaglio surface of the framework significantly reduced the mean fatigue loads at which chipping of veneers occurred, as compared to crowns whose intaglio surface had only been cleaned with alcohol. For this cement glazing or sandblasting the intaglio surface of the crown is not recommended. PMID- 26266656 TI - Influence of Staining Solution and Bleaching on Color Stability of Resin Used for Caries Infiltration. AB - OBJECTIVE: The objective of this study was to evaluate the color stability of Icon-infiltrated white spot lesions after staining and the bleaching effect on the infiltrated and stained surfaces. METHODS AND MATERIALS: Enamel-dentin specimens (N=30, 5 * 5 * 3 mm, 1-mm enamel + 2-mm dentin thickness) were prepared from bovine incisors and randomly allocated into three groups (n=10): control, demineralized, and infiltrated. Artificial enamel subsurface lesions were created using 50 mL of 0.05 M acetate buffer solution. Specimens were produced by Icon application in enamel caries-like lesions, according to the manufacturer's instruction. Baseline color readings were assessed using a spectrophotometer, and CIE L*a*b* measurements of each specimen were performed using a white background. To simulate extrinsic dietary staining, specimens were placed into a 4-mL coffee infusion, three times daily for 15 minutes, for 14 days. After the staining procedure, color measurements were performed again. Then, bleaching procedures were performed using 16% carbamide peroxide gel for four hours daily for 21 days, and a final color assessment was performed. To compare the baseline and final measurements, t-test was used (alpha =0.05). The statistical comparison between the groups was performed using the one-way analysis of variance and Tukey tests (alpha =0.05). RESULTS: Coffee staining provided a significant reduction of L* values and an increase of a* and b* in all groups (control, decayed, and infiltrated). The bleaching procedure provided a significant increase in L* and decrease of a* and b* values in all groups. There was no significant difference in DeltaE values between decayed and infiltrated groups before bleaching, and after bleaching, the infiltrated group showed the lowest DeltaE values. CONCLUSION: It can be concluded that enamel infiltrated with Icon presents significant alteration of color after staining when compared with sound enamel. However, if there is discoloration of the infiltrant, the bleaching treatment can be used successfully. PMID- 26266657 TI - Strengthening of Porcelain Provided by Resin Cements and Flowable Composites. AB - This study evaluated the effect of mechanical properties of resin-based luting agents on the strength of resin-coated porcelain. The luting agents tested were two flowable resin composites (Filtek Z350 Flow and Tetric-N Flow), a light-cured resin cement (Variolink Veneer [VV]), and a dual-cured resin cement (Variolink II) in either light-cured (base paste) or dual-cured (base + catalyst pastes [VD]) mode. Flexural strength (sigmaf) and modulus of elasticity (Ef) of the luting agents were measured in three-point bending mode (n=5). Porcelain discs (Vita VM7) were tested either untreated (control) or acid etched, silanized, and coated with the luting agents. Biaxial flexural strength (sigmabf) of the porcelain discs was tested using a ball-on-ring setup (n=30). The sigmabf of the resin-coated specimens was calculated at z-axial positions for multilayer specimens in the ball-on-ring test: position z = 0 (ceramic surface at the bonded interface) and position z = -t2 (luting agent surface above ring). The sigmaf and Ef data were subjected to analysis of variance and the Student-Newman-Keuls test (alpha=0.05). A Weibull analysis was performed for sigmabf data. Weibull modulus (m) and characteristic strength (sigma0) were calculated. Linear regression analyses investigated the relationship between mechanical properties of the luting agents and the strengthening of porcelain. VD had higher and VV had lower mechanical strength than the other materials. At z = 0, all resin-coated groups had higher sigmabf than the control group. No significant differences between the luting agents were observed for sigmabf and sigma0. At z = -t2, VD had the highest sigmabf and sigma0, whereas VV had the poorest results. No significant differences in m were observed across groups. A linear increase in flexural strength of the porcelain was associated with increased sigmaf and Ef of the luting agents at position z = -t2. In conclusion, resin coating and use of luting agents with better physical properties generally improved the mechanical performance of porcelain. PMID- 26266658 TI - Preventive effects of amino-acid-rich elemental diet Elental(r) on chemotherapy induced oral mucositis in patients with colorectal cancer: a prospective pilot study. AB - PURPOSE: The prospective pilot study was designed to evaluate the preventive effects of amino-acid-rich elemental diet (ED), Elental((r)), on chemotherapy induced oral mucositis in patients with colorectal cancer. The factors influencing its efficacy are also investigated. METHODS: A total of 22 eligible patients with colorectal cancer experiencing grade 1-3 oral mucositis during treatment with fluorouracil-based chemotherapy entered the current study. Their average age was 67 years. There were 10 male and 12 female. The PS was 0 in the majority of patients. Patients received two courses of the same chemotherapy regimen and Elental((r)) concurrently after recovery to grade 0 or 1 oral mucositis. RESULTS: FOLFOX6 + bevacizumab in 8 patients, FOLFIRI + bevacizumab in 8 patients, FOLFIRI + panitumumab in 1 patient, FOLFIRI in 1 patient, XELOX + bevacizumab in 2 patients, and S-1 + cetuximab in 2 patients were used as first line (16 cases) or as second-line (6 cases) chemotherapy. Dose reduction of 5 fluorouracil (5-FU) or oral fluoropyrimidine was performed in the 2 patients achieving grade 3 oral mucositis and in the 3 patients achieving grade 2 oral mucositis. The maximum grade of oral mucositis decreased in 18 of the 22 patients during the first treatment course with Elental((r)) (p = 0.0002) and in 20 of the 22 patients in the second course (p < 0.0001). Multivariate analyses found that the dose reduction in 5-FU or oral fluoropyrimidine, ED intake, and the prior administration of ED were each a significant factor for the preventive efficacy on oral mucositis. CONCLUSION: The amino-acid-rich elemental diet Elental((r)) may be useful as a countermeasure for 5-FU-based chemotherapy-induced oral mucositis in patients with colorectal cancer. PMID- 26266659 TI - Elemental diet plus glutamine for the prevention of mucositis in esophageal cancer patients receiving chemotherapy: a feasibility study. AB - PURPOSE: We investigated the effect of glutamine (Gln) and an elemental diet (ED) on chemotherapy-induced oral mucositis in esophageal cancer patients. METHODS: Thirty patients were randomized to the control group (no treatment: n = 10), Gln group (oral intake of 8910 mg Gln/day: n = 10), or Gln plus ED group (total oral intake of 8862 mg Gln/day, including the Gln in ED: n = 10). Oral administration of Gln and ED began 1 week before chemotherapy and continued during treatment. Oral mucositis was evaluated during 2 cycles of chemotherapy using Common Terminology Criteria for Adverse Events v3.0. RESULTS: The incidence of grade >=2 oral mucositis was 60 % in the control group, 70 % in the Gln group, and 10 % in the Gln plus ED group. Gln plus ED showed a significant preventive effect on the development and severity of oral mucositis. By multivariate analysis, Gln plus ED and cancer stage were independent factors affecting chemotherapy-induced oral mucositis. The percentage of change in body weight and diamine oxidase activity from before chemotherapy was higher in the Gln plus ED group than in the control group. CONCLUSIONS: Oral administration of Gln plus ED may prevent chemotherapy induced oral mucositis in esophageal cancer patients. PMID- 26266660 TI - Understanding domains of health-related quality of life concerns of Singapore Chinese patients with advanced cancer: a qualitative analysis. AB - PURPOSE: Quality of life concerns in patients with advanced diseases might be different from other patients and are shaped by sociocultural context. The objective of this qualitative study was to identify domains and themes of health related quality of life (HRQoL) that Chinese patients with advanced cancer in Singapore considered relevant and important. METHODS: English- and Chinese speaking patients with advanced solid cancer were recruited from a tertiary cancer center and a community-based hospice for in-depth interview or focused group discussion. Thematic analysis was used to identify subthemes, themes, and domains from the transcripts. RESULTS: Forty-six ethnic Chinese (aged 26-86, 48% male) participated in the study. Six domains of HRQoL concerns were identified: pain and suffering, physical health, social health, mental health, financial well being, and spiritual health. Pain and suffering are not limited to the physical domain, reflecting the multidimensional nature of this concept. Pain and suffering must also be understood within the cultural context. Healthcare relations (i.e., social health), existential well-being and religious well-being (i.e., spiritual health), and suffering (i.e., pain and suffering) are not fully captured in the existing HRQoL instruments. In addition, financial issues and the practice of secrecy in interpersonal relationships emerged as unique features possibly arising from our sociocultural context and healthcare financing landscape. CONCLUSION: Socioculturally specific issues not measured by the existing HRQoL instruments for use in patients with advanced cancers or terminal diseases were found in our study. These are non-physical pain and suffering, meaning of illness, meaning of death, financial issues, and practice of secrecy in interpersonal relationships. PMID- 26266661 TI - Post-transcriptional regulation tends to attenuate the mRNA noise and to increase the mRNA gain. AB - Post-transcriptional regulation is ubiquitous in prokaryotic and eukaryotic cells, but how it impacts gene expression remains to be fully explored. Here, we analyze a simple gene model in which we assume that mRNAs are produced in a constitutive manner but are regulated post-transcriptionally by a decapping enzyme that switches between the active state and the inactive state. We derive the analytical mRNA distribution governed by a chemical master equation, which can be well used to analyze the mechanism of how post-transcription regulation influences the mRNA expression level including the mRNA noise. We demonstrate that the mean mRNA level in the stochastic case is always higher than that in the deterministic case due to the stochastic effect of the enzyme, but the size of the increased part depends mainly on the switching rates between two enzyme states. More interesting is that we find that in contrast to transcriptional regulation, post-transcriptional regulation tends to attenuate noise in mRNA. Our results provide insight into the role of post-transcriptional regulation in controlling the transcriptional noise. PMID- 26266663 TI - Improved disease-free survival and overall survival after fluorescence-guided surgery of liver metastasis in an orthotopic nude mouse model. AB - BACKGROUND: In the present study, we sought to determine if fluorescence-guided surgery (FGS) would improve survival compared to standard bright light surgery (BLS) in an experimental colorectal liver metastasis nude mouse model. METHODS: Orthotopic nude-mouse models of human HT-29-GFP colon cancer liver metastasis were established in the left lobe of the liver of mice. Fourteen mice with a single liver metastasis were randomized into FGS or BLS groups of seven each. FGS of liver metastasis was performed using a hand-held portable fluorescence imaging system (Dino-Lite) to visualize the GFP fluorescence of the metastasis. The BLS- and FGS-treated mice were followed by weekly fluorescence imaging in order to detect recurrence. RESULTS: The bright fluorescence of GFP provided sufficient illumination to accurately distinguish the margins of the metastasis within the liver. Recurrence occurred in multiple sites including the liver, lung, and other organs in the BLS-treated mice but was significantly reduced in FGS-treated mice. The FGS-treated mice had significantly prolonged disease-free survival (P = 0.001) and overall survival (P = 0.027) compared to BLS-treated mice. CONCLUSION: The results of the present report demonstrate the feasibility and efficacy of FGS for liver metastasis and suggest its important clinical potential. PMID- 26266664 TI - Gleason and Fuhrman no longer make the grade. AB - Grading is an important prognostic parameter for prostate adenocarcinoma and renal cell carcinoma (RCC); however, the most frequently used classifications fail to account for advances in our understanding of the diagnostic features, classification and/or behaviour of these tumours. In 2005 and 2014, the International Society of Urological Pathology (ISUP) proposed changes to Gleason scoring with the adoption of the ISUP grading for prostate cancer in 2014 (grade 1, score 3 + 3; grade 2, score 3 + 4; grade 3, score 4 + 3; grade 4, score 8; grade 5, score 9-10). Internationally the Fuhrman grading system is widely employed despite criticisms related to its application, validity, and reproducibility. In 2012, the ISUP established a grading system for RCC (grade 1, the nucleolus is not seen or is inconspicuous and basophilic at *400 magnification; grade 2, nucleoli are eosinophilic and clearly visible at *400 magnification; grade 3, nucleoli are clearly visible at *100 magnification; grade 4, tumours show extreme pleomorphism or rhabdoid and/or sarcomatoid morphology). This grading has been validated for clear cell RCC and papillary RCC. It was further recommended that chromophobe RCC not be graded. For other morphotypes of RCC, ISUP grading has not been validated as a prognostic parameter, but can be used for descriptive purposes. PMID- 26266665 TI - Effect of three different chin-down maneuvers on swallowing pressure in healthy young adults. AB - OBJECTIVES/HYPOTHESIS: To determine the effects of three different chin-down maneuvers on swallowing pressure (SP) in healthy young adults using high resolution manometry (HRM). STUDY DESIGN: Repeated measures with subjects serving as their own controls. METHODS: Twenty-six healthy subjects (average age 26.4 [range 21-35] years) swallowed 5 mL of cold water to examine the maximum swallowing pressure (MSP) at the velopharynx, meso-hypopharynx, and upper esophageal sphincter (UES), and to determine the duration of lowered SP at the UES using HRM. The subjects swallowed in the neutral position as a control and in the following three chin-down positions: 1) head flexion (HF); 2) neck flexion (NF); and 3) combined head and neck flexion (HFNF). RESULTS: The MSP at the velopharynx and meso-hypopharynx did not significantly differ among the three chin-down positions. Upon swallowing in the NF posture, the MSP was significantly lower (P < 0.0001) at the UES, and the duration of the lowered SP at the UES was significantly prolonged (P = 0.0010) compared to the neutral position. In comparison, the duration of lowered SP at the UES was significantly (P = 0.0001) shorter in the HF position than in the neutral position. Moreover, the HFNF position significantly (P = 0.0276) lowered the MSP at the UES compared to the control position. CONCLUSION: In young healthy adults, NF maneuver resulted in significantly lower MSP and longer duration of the lowered swallowing pressure at the UES, which might assist bolus passage through the UES. LEVEL OF EVIDENCE: 3b. PMID- 26266666 TI - Acute postoperative pain in children. PMID- 26266667 TI - Reply to: Acute postoperative pain in children. PMID- 26266669 TI - Filament-Assisted Impulsive Raman Spectroscopy of Ozone and Nitrogen Oxides. AB - The filament-assisted impulsive Raman spectra of ozone, nitric oxide, and nitrogen dioxide are presented. The Raman response as a function of ozone concentration scales as N(2), where N is the number of oscillators in the interaction region. The system described has a detection limit of ~300 ppm for gas-phase ozone. Ozone produced via the strong field chemistry occurring within the filament pump was also detected. The measurements reveal spectral interference in the Raman features. Simulations show the spectral fringing results from interference of the Raman signal with pump-induced cross-phase modulation. The fringes are used to classify the symmetric mode of the low concentration filament-generated ozone. PMID- 26266670 TI - Multiple cutaneous lymphoproliferative disorders showing a retained tumor clone by T-cell receptor gene rearrangement analysis: a case series of four patients and review of the literature. AB - BACKGROUND: Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma (CTCL), followed by CD30+ lymphoproliferative disorders, including lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (pcALCL). The objective was to report on a series of patients with different types of CTCL at different times in their clinical course, with a focus on clonality studies. METHODS: Four patients with multiple diagnoses of CTCLs were identified. The clinical information, treatment interventions, and histopathology were reviewed. T-cell receptor (TCR) gene rearrangement studies were performed on all available specimens. RESULTS: The four patients carried diagnoses of: (1) pcALCL and MF; (2) pcALCL, LyP, and pcALCL; (3) LyP, MF, and pcALCL; (4) LyP, pcALCL, and MF; each with characteristic presentation and histopathologic findings. The results of the TCR polymerase chain reaction showed that all tumors expressed and retained a TCR clone(s) as follows: (1) biallelic clone; (2) single clone; (3) biallelic clone with additional clone; and (4) single clone, respectively. CONCLUSION: We report a series of four cases of individual patients with coexisting diagnoses of some combination of MF, LyP, and pcALCL, whose lesions presented in nontraditional sequence and demonstrated a retained clone by gene rearrangement analysis. PMID- 26266671 TI - Infrared Colloidal Quantum Dot Photovoltaics via Coupling Enhancement and Agglomeration Suppression. AB - Materials optimized for single-junction solar spectral harvesting, such as silicon, perovskites, and large-band-gap colloidal quantum dot solids, fail to absorb the considerable infrared spectral energy that lies below their respective band gap. Here we explore through modeling and experiment the potential for colloidal quantum dots (CQDs) to augment the performance of solar cells by harnessing transmitted light in the infrared. Through detailed balance modeling, we identify the CQD band gap that is best able to augment wafer-based, thin-film, and also solution-processed photovoltaic (PV) materials. The required quantum dots, with an excitonic peak at 1.3 MUm, have not previously been studied in depth for solar performance. Using computational studies we find that a new ligand scheme distinct from that employed in better-explored 0.95 MUm band gap PbS CQDs is necessary; only via the solution-phase application of a short bromothiol can we prevent dot fusion during ensuing solid-state film treatments and simultaneously offer a high valence band-edge density of states to enhance hole transport. Photoluminescence spectra and transient studies confirm the desired narrowed emission peaks and reduced surface-trap-associated decay. Electronic characterization reveals that only through the use of the bromothiol ligands is strong hole transport retained. The films, when used to make PV devices, achieve the highest AM1.5 power conversion efficiency yet reported in a solution-processed material having a sub-1 eV band gap. PMID- 26266672 TI - [Hometreatment- an effective alternative to inpatient treatment in child and adolescent psychiatry?]. AB - In many countries hometreatment (HT) offers a cost-effective alternative to hospitalization for children and adolescents with mental health problems requiring intensive mental healthcare. However, the database on HT varies as HT may refer to different models and settings of intensive outpatient treatment. In Germany HT is not used routinely in mental healthcare in child and adolescent psychiatry, therefore the data on HT in Germany, especially in child and adolescent psychiatry, are scarce although funding for studies investigating the effectiveness of HT is available. This review represents a comprehensive search in electronic databases (1980-2014) of literature on HT. It provides as well an overview of the underlying concepts of and the present evidence for HT. In addition, the evidence base on HT for specific child and adolescent mental health disorders is reviewed. Future prospects for the development of HT in Germany facing the upcoming change in health service commissioning (PEPP = "pauschalierendes Entgeltsystem in Psychiatric und Psychosomatik>>) are discussed, as HT in child and adolescent psychiatry, when accurately indicated, can be a valid alternative to inpatient treatment. PMID- 26266673 TI - [The methodological assessment and qualitative evaluation of psychometric performance tests based on the example of modern tests that assess reading and spelling skills]. AB - This article looks at a means of objectively evaluating the quality of psychometric tests. This approach enables users to evaluate psychometric tests based on their methodological characteristics, in order to decide which instrument should be used. Reading and spelling assessment tools serve as examples. The paper also provides a review of German psychometric tests for the assessment of reading and spelling skills. This method facilitates the identification of psychometric tests.of high methodological quality which can be used for the assessment of reading and spelling skills. Reading performance should ideally be assessed with the following instruments: ELFE 1-6, LGVT 6-12, LESEN 6-7, LESEN 8-9, or WLLP-R. The tests to be used for the evaluation of spelling skills are DERET 1-2+, DERET 3-4+, WRT 1+, WRT 2+, WRT 3+, WRT 4+ or HSP 1-10. PMID- 26266674 TI - Diffuse cutaneous leishmaniasis in coexistence with leprosy. AB - Cutaneous leishmaniasis and leprosy are diseases both caused by intracellular pathogens that represent a major health predicament even today. Both these diseases have some characteristics in common, such as the involvement of mucocutaneous tissue, a course with a chronic granulomatous response, a broad clinical spectrum in relation to the host's immunity, and they often affect the poor population in tropical countries. Co-infection of the two diseases, although known to occur, is rarely encountered and reported. Even though new cases of leprosy are diagnosed in the region of coastal Karnataka of India, cutaneous leishmaniasis is rarely reported. We hereby describe a patient who presented with concurrent leprosy and diffuse cutaneous leishmaniasis. PMID- 26266675 TI - Inhibin B, AMH, but not INSL3, IGF1 or DHEAS support differentiation between constitutional delay of growth and puberty and hypogonadotropic hypogonadism. AB - In pre-pubertal boys >= 14 years, the differentiation between constitutional delay of growth and puberty (CDGP) and hypogonadotropic hypogonadism (HH) is challenging, as current diagnostic tools have limitations in sensitivity and specificity. The aim of this study was to assess the usefulness of markers of gonadal activity, growth axis activation and adrenarche in differentiation between pre-pubertal CDGP and HH. This retrospective study was carried out between 2006 and 2015 in an academic out-patient referral centre. The clinical data of 94 boys, aged 13.9-23.2 years and referred for "pubertal delay" were reviewed. Definite diagnoses were established on initial work-up and clinical follow-up: 24 boys were diagnosed with HH, 22 boys with CDGP, pre-pubertal (PP CDGP) at referral and 28 boys with CDGP, early pubertal at referral (EP CDGP), the latter serving as control group. Twenty patients were excluded from evaluation because of previous sex steroid treatment or associated chronic disease. Inhibin B and AMH were measured in all (n = 74); INSL3, IGF1, IGFBP3 and DHEAS in a subset of patients (n = 45) in serum of first presentation. Inhibin B and AMH were higher in boys with PP CDGP than in boys with HH: inhibin B: 87.6 +/ 42.5 vs. 19.8 +/- 13.9 pg/mL; p < 0.001; AMH: 44.9 +/- 27.1 vs. 15.4 +/- 8.3 ng/mL; p < 0.001. Receiver operating characteristics (ROC) for the diagnosis of PPCDGP vs. HH (inhibin B >= 28.5 pg/mL): sensitivity: 95%, specificity: 75%; AUC: 0.955. In combination with an AMH cut-off >=20 ng/mL the specificity increased to 83%. INSL3, IGF1, IGFBP3 and DHEAS levels were not different. In boys with EP CDGP, inhibin B and IGF1 levels were highest (138.7 +/- 59.9 pg/mL/289.7 +/- 117 ng/mL), whereas AMH levels were lowest (11.7 +/- 9.1 ng/mL). Sertoli cell markers are helpful for establishing a prognosis, whether a boy with pubertal delay will enter puberty spontaneously, whereas Leydig cell, growth and adrenal markers are not. PMID- 26266676 TI - A Desulfonylative Approach in Oxidative Gold Catalysis: Regiospecific Access to Donor-Substituted Acyl Gold Carbenes. AB - Donor-substituted acyl gold carbenes are challenging to access selectively by gold-promoted intermolecular oxidation of internal alkynes as the opposite regioisomers frequently predominate. By using alkynyl sulfones or sulfonates as substrates, the oxidative gold catalysis in the presence of substituted pyridine N-oxides offers regiospecific access to acyl/aryl, acyl/alkenyl, and acyl/alkoxy gold carbenes by in situ expulsion of sulfur dioxide. The intermediacies of these reactive species are established by their reactivities, including undergoing further oxidation by the same oxidant, cyclopropanation of styrenes, engaging in a [3+2] cycloaddition with alpha-methylstyrene, and conversion into dienones. PMID- 26266678 TI - Calcifying Fibrous Pseudotumor of the Pleura. PMID- 26266677 TI - Observed surface lysine acetylation of human carbonic anhydrase II expressed in Escherichia coli. AB - Acetylation of surface lysine residues of proteins has been observed in Escherichia coli (E. coli), an organism that has been extensively utilized for recombinant protein expression. This post-translational modification is shown to be important in various processes such as metabolism, stress-response, transcription, and translation. As such, utilization of E. coli expression systems for protein production may yield non-native acetylation events of surface lysine residues. Here we present the crystal structures of wild-type and a variant of human carbonic anhydrase II (hCA II) that have been expressed in E. coli and exhibit surface lysine acetylation and we speculate on the effect this has on the conformational stability of each enzyme. Both structures were determined to 1.6 A resolution and show clear electron density for lysine acetylation. The lysine acetylation does not distort the structure and the surface lysine acetylation events most likely do not interfere with the biological interpretation. However, there is a reduction in conformational stability in the hCA II variant compared to wild type (~ 4 degrees C decrease). This may be due to other lysine acetylation events that have occurred but are not visible in the crystal structure due to intrinsic disorder. Therefore, surface lysine acetylation events may affect overall protein stability and crystallization, and should be considered when using E. coli expression systems. PMID- 26266679 TI - A new impact factor: what we are proud of and where we are heading. PMID- 26266680 TI - Late-onset systemic lupus erythematosus: clinical manifestations, course, and prognosis. PMID- 26266681 TI - CHA2DS2-VASc: towards a universal risk assessment in cardiovascular diseases? PMID- 26266682 TI - Abnormal serum free light chain ratio does not always indicate monoclonal gammopathy. PMID- 26266683 TI - Mortality in end-stage renal disease: the importance of the genetic background. PMID- 26266684 TI - In search for a biochemical marker of overhydration in hemodialysis: the "magic bullet" yet to be found. PMID- 26266685 TI - NT-proBNP: a biomarker with new potential application. PMID- 26266686 TI - Warning: hijacked journals. PMID- 26266687 TI - Surface-Enhanced Raman Scattering Based on Controllable-Layer Graphene Shells Directly Synthesized on Cu Nanoparticles for Molecular Detection. AB - Graphene shells with a controllable number of layers were directly synthesized on Cu nanoparticles (CuNPs) by chemical vapor deposition (CVD) to fabricate a graphene-encapsulated CuNPs (G/CuNPs) hybrid system for surface-enhanced Raman scattering (SERS). The enhanced Raman spectra of adenosine and rhodamine 6G (R6G) showed that the G/CuNPs hybrid system can strongly suppress background fluorescence and increase signal-to-noise ratio. In four different types of SERS systems, the G/CuNPs hybrid system exhibits more efficient SERS than a transferred graphene/CuNPs hybrid system and pure CuNPs and graphene substrates. The minimum detectable concentrations of adenosine and R6G by the G/CuNPs hybrid system can be as low as 10(-8) and 10(-10) M, respectively. The excellent linear relationship between Raman intensity and analyte concentration can be used for molecular detection. The graphene shell can also effectively prevent surface oxidation of Cu nanoparticles after exposure to ambient air and thus endow the hybrid system with a long lifetime. This work provides a basis for the fabrication of novel SERS substrates. PMID- 26266688 TI - Spatiotemporal closure of fractional laser-ablated channels imaged by optical coherence tomography and reflectance confocal microscopy. AB - BACKGROUND AND OBJECTIVE: Optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) offer high-resolution optical imaging of the skin, which may provide benefit in the context of laser-assisted drug delivery. We aimed to characterize postoperative healing of ablative fractional laser (AFXL) induced channels and dynamics in their spatiotemporal closure using in vivo OCT and RCM techniques. STUDY DESIGN/MATERIALS AND METHODS: The inner forearm of healthy subjects (n = 6) was exposed to 10,600 nm fractional CO2 laser using 5 and 25% densities, 120 MUm beam diameter, 5, 15, and 25 mJ/microbeam. Treatment sites were scanned with OCT to evaluate closure of AFXL-channels and RCM to evaluate subsequent re-epithelialization. RESULTS: OCT and RCM identified laser channels in epidermis and upper dermis as black, ablated tissue defects surrounded by characteristic hyper-and hyporeflective zones. OCT imaged individual laser channels of the entire laser grid, and RCM imaged epidermal cellular and structural changes around a single laser channel to the depth of the dermoepidermal junction (DEJ) and upper papillary dermis. OCT images visualized a heterogeneous material in the lower part of open laser channels, indicating tissue fluid. By OCT the median percentage of open channels was evaluated at several time points within the first 24 hours and laser channels were found to gradually close, depending on the used energy level. Thus, at 5 mJ/microbeam, 87% (range 73-100%) of channels were open one hour after laser exposure, which declined to 27% (range 20-100%) and 20% (range 7-93%) at 12 and 24 hours after laser exposure, respectively. At 25 mJ/microbeam, 100% (range 100-100%) of channels were open 1 hour after laser exposure while 53% (range 33-100%) and 40% (range 0-100%) remained open at 12 and 24 hours after exposure. Median depth and width of open channels decreased over time depending of applied energy. RCM verified initial re-epithelialization from day 2 for all energy levels used. Morphology of ablation defects by OCT and RCM corresponded to histological assessments. CONCLUSIONS: OCT and RCM enabled imaging of AFXL-channels and their spatiotemporal closure. Laser channels remained open up to 24 hours post laser, which may be important for the time perspective to deliver topical substances through AFXL channels. PMID- 26266689 TI - Comment on "MALDI-MS Imaging Analysis of Fungicide Residue Distributions on Wheat Leaf Surfaces". PMID- 26266690 TI - Response to Comment on "MALDI-MS Imaging Analysis of Fungicide Residue Distributions on Wheat Leaf Surfaces". PMID- 26266691 TI - Fate of PBDEs during food processing: Assessment of formation of mixed chlorinated/brominated diphenyl ethers and brominated dioxins/furans. AB - The aim of this study was to evaluate effects of food processing on PBDE levels, in particular influence of heat treatment on degradation of PBDEs, including possible formation of chlorinated diphenyl ethers or brominated dioxins/furans as degradation products. It was shown that PBDEs heated in the presence of chlorine (from either organic or inorganic sources) formed mixed chlorinated/brominated diphenyl ethers. However, no PCDEs were formed in the presence of lipids. Lipid medium increased stability of PBDEs exposed to UV irradiation. Profile of congeners formed in result of the debromination reaction was significantly different than profiles observed by some other authors in aliphatic organic solvents. Grilling processes increased concentrations (calculated on the fresh product basis) of the studied compounds by 4-8/22-34% for electric/coal grill, respectively. Depending on the congener and on the applied heat treatment, PBDE mass in pork meat after grilling dropped by 26-53%. No detectable quantities of either brominated dioxins or furans were formed during thermal processing of food containing typical levels of PBDEs. PMID- 26266692 TI - Mutations Proximal to Sites of Autoproteolysis and the alpha-Helix That Co-evolve under Drug Pressure Modulate the Autoprocessing and Vitality of HIV-1 Protease. AB - N-Terminal self-cleavage (autoprocessing) of the HIV-1 protease precursor is crucial for liberating the active dimer. Under drug pressure, evolving mutations are predicted to modulate autoprocessing, and the reduced catalytic activity of the mature protease (PR) is likely compensated by enhanced conformational/dimer stability and reduced susceptibility to self-degradation (autoproteolysis). One such highly evolved, multidrug resistant protease, PR20, bears 19 mutations contiguous to sites of autoproteolysis in retroviral proteases, namely clusters 1 3 comprising residues 30-37, 60-67, and 88-95, respectively, accounting for 11 of the 19 mutations. By systematically replacing corresponding clusters in PR with those of PR20, and vice versa, we assess their influence on the properties mentioned above and observe no strict correlation. A 10-35-fold decrease in the cleavage efficiency of peptide substrates by PR20, relative to PR, is reflected by an only ~4-fold decrease in the rate of Gag processing with no change in cleavage order. Importantly, optimal N-terminal autoprocessing requires all 19 PR20 mutations as evaluated in vitro using the model precursor TFR-PR20 in which PR is flanked by the transframe region. Substituting PR20 cluster 3 into TFR-PR (TFR-PR(PR20-3)) requires the presence of PR20 cluster 1 and/or 2 for autoprocessing. In accordance, substituting PR clusters 1 and 2 into TFR-PR20 affects the rate of autoprocessing more drastically (>300-fold) compared to that of TFR-PR(PR20-3) because of the cumulative effect of eight noncluster mutations present in TFR-PR20(PR-12). Overall, these studies imply that drug resistance involves a complex synchronized selection of mutations modulating all of the properties mentioned above governing PR regulation and function. PMID- 26266693 TI - Managing Stigma: Disclosure-Response Communication Patterns in Pro-Anorexic Websites. AB - Pro-anorexic websites are a popular online venue for individuals with anorexia, but recent research suggests that they play a role of "online negative enabling support groups" because they can undermine recovery and encourage negative behaviors by validating pro-anorexic views. By analyzing 22,811 messages from 5,590 conversations from the Pro-Ana Nation online discussion board forum, this study examines communicative mechanisms of online negative enabling support through language analysis of disclosure-response sequences, changes in the language of the initial discloser within an interaction exchange, and the role of responses in eliciting those changes. The findings show that initiating disclosures containing stigma-related emotion words, anorexia-specific content, and sociorelational content are typically met with negatively valenced responses from other members of the pro-anorexic community. Moreover, although the act of revealing stigmatized information has some cathartic effects, disclosers use more, not fewer, stigma-related emotion words when they receive negatively valenced responses. These results provide insight into communicative dynamics and effects of online negative enabling support through validation of the pro anorexic identity and the dangerous cycle of stigma escalation in disclosure response exchanges on pro-anorexic online communities. PMID- 26266694 TI - A [2 + 3] Reductive Cyclodimerization of Quinoline by SmI2. AB - Pyridine and its derivatives are rather difficult to reduce, and the products often undergo a very fast reoxidation to regain aromaticity. The reduction of quinoline by SmI2 results in an instantaneous [2 + 3] cyclization reaction, forming a bridged seven-membered ring within a polycyclic system. PMID- 26266695 TI - Enhanced Electroresponse of Alkaline Earth Metal-Doped Silica/Titania Spheres by Synergetic Effect of Dispersion Stability and Dielectric Property. AB - A series of alkaline earth metal-doped hollow SiO2/TiO2 spheres (EM-HST) are prepared as electrorheological (ER) materials via sonication-mediated etching method with various alkaline earth metal hydroxides as the etchant. The EM-HST spheres are assessed to determine how their hollow interior and metal-doping affects the ER activity. Both the dispersion stability and the dielectric properties of these materials are greatly enhanced by the proposed one-step etching method, which results in significant enhancement of ER activity. These improvements are attributed to increased particle mobility and interfacial polarization originating from the hollow nature of the EM-HST spheres and the effects of EM metal-doping. In particular, Ca-HST-based ER fluid exhibits ER performance which is 7.1-fold and 3.1-fold higher than those of nonhollow core/shell silica/titania (CS/ST) and undoped hollow silica/titania (HST)-based ER fluids, respectively. This study develops a versatile and simple approach to enhancing ER activity through synergetic effects arising from the combination of dispersion stability and the unique dielectric properties of hollow EM-HST spheres. In addition, the multigram scale production described in this experiment can be an excellent advantage for practical and commercial ER application. PMID- 26266696 TI - Erythema Multiforme Associated with Respiratory Disease in a Commercial Breeding Pig Herd. AB - This study describes an erythema multiforme (EM) in breeding sows, after their mixing in the group housing system. Sows at 30-35 days of gestation showed red and raised skin areas, depression, anorexia, fever, respiratory problems, and increased return to estrus. Blood and nasal samples from diseased sows were examined by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay for respiratory pathogens. Hematological and biochemical analyses were performed on the blood samples. From diseased sows, vaginal swabs for microbiological examinations and samples at slaughterhouse for gross and microscopic examinations were collected. Samples from the complete gestation and lactation feed were examined for mycotoxins. All sampled sows were seropositive for Actinobacillus pleuropneumoniae (App) and porcine reproductive and respiratory syndrome virus (PRRSV). No viremia for PRRSV and porcine circovirus type 2 were detected. All nasal samples were positive for Streptococcus suis, one for Swine Influenza Virus and one for App, Hemophilus parasuis, and S. suis. In all vaginal swabs, Escherichia coli and Streptococcus spp. were detected. Diseased sows had moderate leukocytosis, mild anemia, and thrombocytopenia. No mycotoxins were detected in feed. Histopathological examination revealed increased vascularization of the superficial and middle dermis. EM was likely due to illness caused by viral and bacterial infections. This study suggests that stress caused by the sows' mixing might have triggered the problem. PMID- 26266697 TI - Determination of iron content and dispersity of intact ferritin by superconducting tunnel junction cryodetection mass spectrometry. AB - Ferritin is a common iron storage protein complex found in both eukaryotic and prokaryotic organisms. Although horse spleen holoferritin (HS-HoloFt) has been widely studied, this is the first report of mass spectrometry (MS) analysis of the intact form, likely because of its high molecular weight ~850 kDa and broad iron-core mass distribution. The 24-subunit ferritin heteropolymer protein shell consists of light (L) and heavy (H) subunits and a ferrihydrite-like iron core. The H/L heterogeneity ratio of the horse spleen apoferritin (HS-ApoFt) shell was found to be ~1:10 by liquid chromatography-electrospray ionization mass spectrometry. Superconducting tunneling junction (STJ) cryodetection matrix assisted laser desorption ionization time-of-flight MS was utilized to determine the masses of intact HS-ApoFt, HS-HoloFt, and the HS-HoloFt dimer to be ~505 kDa, ~835 kDa, and ~1.63 MDa, respectively. The structural integrity of HS-HoloFt and the proposed mineral adducts found for both purified L and H subunits suggest a robust biomacromolecular complex that is internally stabilized by the iron-based core. However, cross-linking experiments of HS-HoloFt with glutaraldehyde, unexpectedly, showed the complete release of the iron-based core in a one-step process revealing a cross-linked HS-ApoFt with a narrow fwhm peak width of 31.4 kTh compared to 295 kTh for HS-HoloFt. The MS analysis of HS-HoloFt revealed a semiquantitative description of the iron content and core dispersity of 3400 +/- 1600 (2sigma) iron atoms. Commercially prepared HS-ApoFt was estimated to still contain an average of 240 iron atoms. These iron abundance and dispersity results suggest the use of STJ cryodetection MS for the clinical analysis of iron deficient/overload diseases. PMID- 26266699 TI - Efficiency optimisation of proteins on a chip. AB - This study elucidates that the protein reorientation on a chip can be changed by an external electric field (EEF) and optimised for achieving strong effective binding between proteins. Protein A and its binding protein immunoglobulin G (IgG) were used as an example, in addition to an anticancer peptide (CB1a) and its antibody (anti-CB1a). The binding forces (BFs) were measured by atomic force microscopy (AFM) with EEFs applied at different angles (EEF degrees ). The optimal angle (OA) of the EEF (OAEEF degrees ) corresponding to the maximum binding force (BFmax) was obtained. The results showed that the BFmax values between IgG/Protein A and anti-CB1a/CB1a were 6424.2 +/- 195.3 pN (OAEEF degrees = 45 degrees ) and 729.1 +/- 33.2 pN (OAEEF degrees = 22.5 degrees ), respectively. Without an EEF, the BF values were only 730.0 +/- 113.9 pN and 337.3 +/- 35.0 pN, respectively. Based on these observations, we concluded that the efficient optimisation of protein-protein interaction on a chip is essential. This finding is applicable to the industrial fabrication of all protein chips. PMID- 26266698 TI - Iron(II) Active Species in Iron-Bisphosphine Catalyzed Kumada and Suzuki-Miyaura Cross-Couplings of Phenyl Nucleophiles and Secondary Alkyl Halides. AB - While previous studies have identified FeMes2(SciOPP) as the active catalyst species in iron-SciOPP catalyzed Kumada cross-coupling of mesitylmagnesium bromide and primary alkyl halides, the active catalyst species in cross-couplings with phenyl nucleophiles, where low valent iron species might be prevalent due to accessible reductive elimination pathways, remains undefined. In the present study, in situ Mossbauer and magnetic circular dichroism spectroscopic studies combined with inorganic syntheses and reaction studies are employed to evaluate the in situ formed iron species and identify the active catalytic species in iron SciOPP catalyzed Suzuki-Miyaura and Kumada cross-couplings of phenyl nucleophiles and secondary alkyl halides. While reductive elimination to form Fe(eta(6) biphenyl)(SciOPP) occurs upon reaction of FeCl2(SciOPP) with phenyl nucleophiles, this iron(0) species is not found to be kinetically competent for catalysis. Importantly, mono- and bis-phenylated iron(II)-SciOPP species that form prior to reductive elimination are identified, where both species are found to be reactive toward electrophile at catalytically relevant rates. The higher selectivity toward the formation of cross-coupled product observed for the monophenylated species combined with the undertransmetalated nature of the in situ iron species in both Kumada and Suzuki-Miyaura reactions indicates that Fe(Ph)X(SciOPP) (X = Br, Cl) is the predominant reactive species in cross-coupling. Overall, these studies demonstrate that low-valent iron is not required for the generation of highly reactive species for effective aryl-alkyl cross-couplings. PMID- 26266701 TI - In situ ATR-FTIR study of H2O and D2O adsorption on TiO2 under UV irradiation. AB - The adsorption of water and deuterium oxide on TiO2 surfaces was investigated in the dark as well as under UV(A) irradiation using in situ ATR-FTIR spectroscopy under oxygen and oxygen free conditions. Adsorption of H2O-D2O mixtures revealed an isotopic exchange reaction occurring onto the surface of TiO2 in the dark. Under UV(A) irradiation, the amount of both OH and OD groups was found to be increased by the presence of molecular oxygen. Furthermore, the photocatalytic formation of hydroperoxide under oxygenated condition has been recorded utilizing Attenuated Total Reflection Fourier Transformed Infrared (ATR-FTIR) spectroscopy which appeared as new band at 3483 cm(-1). Different possible mechanisms are discussed in terms of the source of hydroxyl groups formed and/or hydration water on the TiO2 surface for the photocatalytic reaction and photoinduced hydrophilicity. PMID- 26266700 TI - Diels-Alder Hydrogels for Controlled Antibody Release: Correlation between Mesh Size and Release Rate. AB - Eight-armed PEG, molecular mass 10 kDa, was functionalized with furyl and maleimide groups, respectively; the obtained macromonomers were cross-linked via Diels-Alder chemistry. The mesh size (xi) of the prepared hydrogels was determined by swelling studies, rheology, and low field NMR spectroscopy. The in vitro release of fluorescein isothiocyanate labeled dextrans (FDs) and bevacizumab was investigated. The average mesh size (xiavg) increased from 5.8 +/ 0.1 nm to 56 +/- 13 nm during degradation, as determined by swelling studies. The result of the rheological measurements (8.0 nm) matched the initial value of xiavg. Low field NMR spectroscopy enabled the determination of the mesh size distribution; the most abundant mesh size was found to be 9.2 nm. In combination with the hydrodynamic radius of the molecule (Rh), the time-dependent increase of xiavg was used to predict the release profiles of incorporated FDs applying an obstruction-scaling model. The predicted release profiles matched the experimentally determined release profiles when Rh < xiavg. However, significant deviations from the theoretical predictions were observed when Rh >= xiavg, most likely due to the statistical distribution of xi in real polymer networks. The release profile of bevacizumab differed from those of equivalently sized FDs. The delayed release of bevacizumab was most likely a result of the globular structure and rigidity of the protein. The observed correlation between xi and the release rate could facilitate the design of controlled release systems for antibodies. PMID- 26266702 TI - Graphene scavenges free radicals to synergistically enhance structural properties in a gamma-irradiated polyethylene composite through enhanced interfacial interactions. AB - A unique strategy for scavenging free radicals in situ on exposure to gamma irradiation in polyethylene (PE) nanocomposites is presented. Blends of ultra high molecular weight PE and linear low-density PE (PEB) and their nanocomposites with graphene (GPEB) were prepared by melt mixing to develop materials for biomedical implants. The effect of gamma irradiation on the microstructure and mechanical properties was systematically investigated. The neat blend and the nanocomposite were subjected to gamma-ray irradiation in order to improve the interfacial adhesion between PE and graphene sheets. Structural and thermal characterization revealed that irradiation induced crosslinking and increased the crystallinity of the polymer blend. The presence of graphene further enhanced the crystallinity via crosslinks between the polymer matrix and the filler on irradiation. Graphene was found to scavenge free radicals as confirmed by electron paramagnetic resonance spectroscopy. Irradiation of graphene-containing polymer composites resulted in the largest increase in modulus and hardness compared to either irradiation or addition of graphene to PEB alone. This study provides new insight into the role of graphene in polymer matrices during irradiation and suggests that irradiated graphene-polymer composites could emerge as promising materials for use as articulating surfaces in biomedical implants. PMID- 26266703 TI - Analysis and Differentiation of Photocopy Toners. AB - The identification and classification of photocopiers presents particular problems for the document examiner. While comparison of defect marks serves to identify copies produced on an individual office copy machine, it is often necessary to eliminate large numbers of machines as possible sources before commencing this detailed examination. Differentiation of toners offers an effective means of achieving this elimination. This review describes the chemical and physical properties of different toners and how these properties can be used for toner discrimination. The chemical composition of bulk toners is outlined together with assessment of the chemical techniques, infrared spectroscopy, pyrolysis mass spectroscopy and energy dispersive x-ray analysis, which have been successfully applied to the analysis of toners removed from copy papers. The different physical properties of toners on paper are related to both their composition and the methods used to fuse toners to the paper. Simple observations such as color, texture and surface appearance, made visible by low power microscopy, offer much discrimination; more can be achieved from examination of magnetic properties and from the use of scanning electron microscopy to study surface morphology. Finally the effectiveness of each technique is assessed and a sequential approach to toner analysis suggested. PMID- 26266704 TI - Hair Protein Polymorphism and Its Application to Forensic Science Hair Comparison. AB - Hair protein is keratin, a hard protein which is naturally insoluble and resistant to attack by proteolytic enzymes. Keratin exhibits a lot of heterogeneity when it is reduced at the disulfide cross linkages. This nature of heterogeneity can provide forensic scientists who are engaged in hair comparison with information concerning species identification as well as individual discrimination. In this review the hair protein variation based on genetic or acquired origin are discussed critically with special reference to forensic hair comparison. PMID- 26266705 TI - Methods for the Determination of Shooting Distance. AB - The review deals with scientific methods for determining shooting distance. The different procedures are explained, their advantages and disadvantages are discussed. The methods are divided into chemographical processes and spectroscopic techniques. Special emphasis is given to the methods proven to be especially useful in daily work, but methods used in basic research are briefly described as well. Furthermore, attention is paid to newly developed ammunitions. In addition, a survey is given on the chemical elements found in gunshot residences (GSR). PMID- 26266706 TI - Specimen Adulteration in Drug Urinalysis. AB - Data from samples adulterated with a variety of substances have been described with respect to their effects on a number of testing methodologies. Several substances have been shown to produce false negative results while others cause positive results in the screening test. Some adulterants cause samples to be negative because the drug, or metabolites, of interest is changed or destroyed while others effect the assay itself. No evidence exists to suggest that an adulterant can cause a false positive result if good forensic procedures are followed including confirmation of initial positive results using a second methodology based on a different chemical principle such as gas chromatography/mass spectrometry. PMID- 26266707 TI - Changes in the Microenvironment of Nitroxide Radicals around the Glass Transition Temperature. AB - For structural characterization by pulsed EPR methods, spin-labeled macromolecules are routinely studied at cryogenic temperatures. The equilibration of the conformational ensemble during shock-freezing occurs to a good approximation at the glass transition temperature (Tg). In this work, we used X band power saturation continuous wave (cw) EPR to obtain information on the glass transition temperatures in the microenvironment of nitroxide radicals in solvents or bound to different sites in proteins. The temperature dependence of the saturation curve of nitroxide probes in pure glycerol or ortho-terphenyl showed detectable transitions at the respective Tg values, with the latter solvent characterized by a sharper change of the saturation properties, according to its higher fragility. In contrast, nitroxide probes in a glycerol/water mixture showed a discontinuity in the saturation properties close to the expected glass transition temperature, which made the determination of Tg complicated. Low temperature W-band cw EPR and W-band ELDOR-detected NMR experiments demonstrated that the discontinuity is due to local rearrangements of H-bonds between water molecules and the nitroxide reporter group. The change in the network of H-bonds formed between the nitroxide and water molecules that occurs around Tg was found to be site-dependent in spin-labeled proteins. This effect can therefore be modulated by neighboring residues with different steric hindrances and/or charge distributions and possibly by the glycerol enrichment on protein surfaces. In conclusion, if the thermal history of the sample is carefully reproduced, the nitroxide probe is extremely sensitive in reporting site-specific changes in the H-bonding to water molecules close to Tg and local glass transition temperatures in spin-labeled macromolecules. PMID- 26266708 TI - New findings and the current controversies for water oxidation by a copper(ii) azo complex: homogeneous or heterogeneous? AB - In this paper, new findings for the water-oxidizing activity of [(L)Cu(II)(NO3)], (L = (E)-3-(pyridin-2-yldiazenyl)naphthalen-2-ol (HL)) under both electro-water oxidation conditions and in the presence of cerium(iv) ammonium nitrate are reported. PMID- 26266710 TI - The Role of Ligand Packing Frustration in Body-Centered Cubic (bcc) Superlattices of Colloidal Nanocrystals. AB - This paper addresses the assembly of body centered-cubic (bcc) superlattices of organic ligand-coated nanocrystals. First, examples of bcc superlattices of dodecanethiol-capped Au nanocrystals and oleic acid-capped PbS and PbSe nanocrystals are presented and examined by transmission electron microscopy (TEM) and grazing incidence small-angle X-ray scattering (GISAXS). These superlattices tend to orient on their densest (110) superlattice planes and exhibit a significant amount of {112} twinning. The same nanocrystals deposit as monolayers with hexagonal packing, and these thin films can coexist with thicker bcc superlattice layers, even though there is no hexagonal plane in a bcc lattice. Both the preference of bcc in bulk films over the denser face-centered cubic (fcc) superlattice structure and the transition to hexagonal monolayers can be rationalized in terms of packing frustration of the ligands. A model is presented to calculate the difference in entropy associated with capping ligand packing frustration in bcc and fcc superlattices. PMID- 26266709 TI - Sister chromatid decatenation: bridging the gaps in our knowledge. AB - Faithful chromosome segregation is critical in preventing genome loss or damage during cell division. Failure to properly disentangle catenated sister chromatids can lead to the formation of bulky or ultrafine anaphase bridges, and ultimately genome instability. In this review we present an overview of the current state of knowledge of how sister chromatid decatenation is carried out, with particular focus on the role of TOP2A and TOPBP1 in this process. PMID- 26266712 TI - Diffusion-Induced Shape Evolution in Multinary Semiconductor Nanostructures. AB - The classical mechanism of crystal growth for architecting different nanomaterials in solution, although widely studied, is mainly restricted to binary semiconductor systems. However, this method is not applicable to multinary nanomaterials, which have multivalent cations possessing different reactivity under identical reaction conditions. Hence, the shape architectures of these nanostructures, which require a more sophisticated approach, remain relatively unexplored compared to those of binary semiconductors. Owing to the importance of the multinary materials, which are emerging as excellent green materials for both light harvesting and light emission, we investigated the diffusion-rate controlled formation of ternary AgGaSe2 nanostructures and studied their heterostructures with noble metals. Controlling the changes in the rate of diffusion of the Ag ions resulted in the formation of tadpole-shaped AgGaSe2 ternary nanostructures. In situ study by collecting a sequential collection of samples has been carried out, and the conversion of amorphous Ga-selenide to crystalline AgGaSe2 has been monitored. In addition, heterostructures of tadpole AgGaSe2 with noble metals, Au and Pt, were designed, and their photocatalytic behaviors were studied. PMID- 26266711 TI - Two-Color Nonlinear Spectroscopy for the Rapid Acquisition of Coherent Dynamics. AB - There has been considerable recent interest in the observation of coherent dynamics in photosynthetic systems by 2D electronic spectroscopy (2DES). In particular, coherences that persist during the "waiting time" in a 2DES experiment have been attributed to electronic, vibrational, and vibronic origins in various systems. The typical method for characterizing these coherent dynamics requires the acquisition of 2DES spectra as a function of waiting time, essentially a 3DES measurement. Such experiments require lengthy data acquisition times that degrade the signal-to-noise of the recorded coherent dynamics. We present a rapid and high signal-to-noise pulse-shaping-based approach for the characterization of coherent dynamics. Using chlorophyll a, we demonstrate that this method retains much of the information content of a 3DES measurement and provides insight into the physical origin of the coherent dynamics, distinguishing between ground and excited state coherences. It also enables high resolution determination of ground and excited state frequencies. PMID- 26266713 TI - Impact of Electrocatalyst Activity and Ion Permeability on Water-Splitting Photoanodes. AB - Electrocatalyst (EC)-modified semiconductor (SC) photoelectrodes are key elements of solar water-splitting systems. The SC|EC interface affects the composite photoelectrode behavior but is poorly understood. We uncover the role of EC activity and SC|EC interface properties using a range of metal (Ni, Fe, Ni-Fe, Co, Ir) oxide or (oxy)hydroxide ECs deposited on model single-crystal n-TiO2 photoanodes. The impedance and photoelectrochemical response of the system was nearly independent of EC oxygen evolution activity if the catalyst was deposited electrochemically as an ion-permeable (oxy)hydroxide or hydrous oxide. When dense oxides (e.g., ion-impermeable) ECs were used, the response depended strongly on the EC. These data demonstrate that the EC and SC interface structures are more important than the EC activity in determining the composite photoanode response, confirming recent SC|EC interface simulations for ion-permeable ECs. These results thus inform the design of high-performance water-oxidizing photoanodes with direct SC|EC interfaces. PMID- 26266714 TI - Conformationally Gated Charge Transfer in DNA Three-Way Junctions. AB - Molecular structures that direct charge transport in two or three dimensions possess some of the essential functionality of electrical switches and gates. We use theory, modeling, and simulation to explore the conformational dynamics of DNA three-way junctions (TWJs) that may control the flow of charge through these structures. Molecular dynamics simulations and quantum calculations indicate that DNA TWJs undergo dynamic interconversion among "well stacked" conformations on the time scale of nanoseconds, a feature that makes the junctions very different from linear DNA duplexes. The studies further indicate that this conformational gating would control charge flow through these TWJs, distinguishing them from conventional (larger size scale) gated devices. Simulations also find that structures with polyethylene glycol linking groups ("extenders") lock conformations that favor CT for 25 ns or more. The simulations explain the kinetics observed experimentally in TWJs and rationalize their transport properties compared with double-stranded DNA. PMID- 26266715 TI - Thermodynamics of Methane Adsorption on Copper HKUST-1 at Low Pressure. AB - Metal-organic frameworks (MOFs) can be engineered as natural gas storage materials by tuning the pore structures and surface properties. Here we report the direct measurement of CH4 adsorption enthalpy on a paddlewheel MOF (Cu HKUST 1) using gas adsorption calorimetry at 25 degrees C at low pressures (below 1 bar). In this pressure region, the CH4-CH4 intermolecular interactions are minimized and the energetics solely reflects the CH4-MOF interactions. Our results suggest moderately exothermic physisorption with an enthalpy of -21.1 +/- 1.1 kJ/mol CH4 independent of coverage. This calorimetric investigation complements previous computational and crystallographic studies by providing zero coverage enthalpies of CH4 adsorption. The analysis of the new and literature data suggests that in initial stages of adsorption the CH4-HKUST-1 interaction tends to be more sensitive to the pore dimension than to the guest polarizability, suggesting a less specific chemical binding role for the open Cu site. PMID- 26266716 TI - Optical and Electronic Properties of Nonconcentric PbSe/CdSe Colloidal Quantum Dots. AB - Lead chalcogenide colloidal quantum dots are attractive candidates for applications operating in the near infrared spectral range. However, their function is forestalled by limited stability under ambient conditions. Prolonged temperature-activated cation-exchange of Cd(2+) for Pb(2+) forms PbSe/CdSe core/shell heterostructures, unveiling a promising surface passivation route and a method to modify the dots' electronic properties. Here, we follow early stages of an-exchange process, using spectroscopic and structural characterization tools, as well as numerical calculations. We illustrate that preliminary-exchange stages involve the formation of nonconcentric heterostructures, presumably due to a facet selective reaction, showing a pronounced change in the optical properties upon the increase of the degree of nonconcentricity or/and plausible creation of core/shell interfacial alloying. However, progressive-exchange stages lead to rearrangement of the shell segment into uniform coverage, providing tolerance to oxygen exposure with a spectral steadiness already on the formation of a monolayer shell. PMID- 26266717 TI - Biological Water or Rather Water in Biology? PMID- 26266718 TI - How Important Is the Organic Part of Lead Halide Perovskite Photovoltaic Cells? Efficient CsPbBr3 Cells. AB - Hybrid organic-inorganic lead halide perovskite photovoltaic cells have already surpassed 20% conversion efficiency in the few years that they have been seriously studied. However, many fundamental questions still remain unanswered as to why they are so good. One of these is "Is the organic cation really necessary to obtain high quality cells?" In this study, we show that an all-inorganic version of the lead bromide perovskite material works equally well as the organic one, in particular generating the high open circuit voltages that are an important feature of these cells. PMID- 26266719 TI - Does Infrared Multiphoton Dissociation of Vinyl Chloride Yield Cold Vinylidene? AB - Velocity map imaging of the infrared multiphoton dissociation of vinyl chloride shows the formation of HCl in rotational levels below J = 10 that are associated with the three-center elimination pathway. The total translational energy release is observed to peak at 3-5 kcal/mol, which is consistent with the low reverse barrier predicted for the formation of HCl with vinylidene coproducts. Direct dynamics trajectory studies from the three-center transition state reproduce the observed distributions and show that the associated vinylidene is formed with only modest rotational excitation, precluding Coriolis-induced mixing among the excited vibrational levels of acetylene that would lead to distribution of vinylidene character into many vibrationally mixed acetylene vibrational levels. The results suggest that infrared multiphoton dissociation of vinyl chloride is an efficient route to synthesis of stable, cold vinylidene. PMID- 26266720 TI - Time-Resolved Photoelectron Spectroscopy of Dissociating 1,2-Butadiene Molecules by High Harmonic Pulses. AB - Using 42 nm high harmonic pulses, the dissociation dynamics of 1,2-butadiene was investigated by time-resolved photoelectron spectroscopy (TRPES), enabling us to observe dynamical changes of multiple molecular orbitals (MOs) with higher temporal resolution than conventional light sources. Because each lower-lying occupied MO has particular spatial electron distribution, the structural dynamics of photochemical reaction can be revealed. On the femtosecond time scale, a short lived excited state with a lifetime of 37 +/- 15 fs and the coherent oscillation of the photoelectron yield stimulated by Hertzberg-Teller coupling were observed. Ab initio molecular dynamics simulations in the electronically excited state find three relaxation pathways from the vertically excited structure in S1 to the ground state, and one of them is the dominant relaxation pathway, observed as the short-lived excited state. On the picosecond time scale, the photoelectron yields related to the C-C bond decreased upon photoexcitation, indicating C-C bond cleavage. PMID- 26266721 TI - Light-Induced Increase of Electron Diffusion Length in a p-n Junction Type CH3NH3PbBr3 Perovskite Solar Cell. AB - High band gap, high open-circuit voltage solar cells with methylammonium lead tribromide (MAPbBr3) perovskite absorbers are of interest for spectral splitting and photoelectrochemical applications, because of their good performance and ease of processing. The physical origin of high performance in these and similar perovskite-based devices remains only partially understood. Using cross-sectional electron-beam-induced current (EBIC) measurements, we find an increase in carrier diffusion length in MAPbBr3(Cl)-based solar cells upon low intensity (a few percent of 1 sun intensity) blue laser illumination. Comparing dark and illuminated conditions, the minority carrier (electron) diffusion length increases about 3.5 times from Ln = 100 +/- 50 nm to 360 +/- 22 nm. The EBIC cross section profile indicates a p-n structure between the n-FTO/TiO2 and p perovskite, rather than the p-i-n structure, reported for the iodide derivative. On the basis of the variation in space-charge region width with varying bias, measured by EBIC and capacitance-voltage measurements, we estimate the net-doping concentration in MAPbBr3(Cl) to be 3-6 * 10(17) cm(-3). PMID- 26266722 TI - In Search for the Best Environment for Single Molecule Studies: Photostability of Single Terrylenediimide Molecules in Various Polymer Matrices. AB - Photobleaching is the main limiting factor in single molecule studies by optical techniques. We investigated the dependence of photostability of terrylene diimide (TDI) derivative on its environment using confocal fluorescence microscopy. Seven different polymers were tested. Depending on the matrix, photobleaching quantum yields vary by 2 orders of magnitude. Their values correlate with parameters characterizing oxygen mobility in polymers: diffusion coefficient and permeability. Poly(vinyl chloride) (PVC) and poly(methyl methacrylate) (PMMA) exhibit the lowest photodestruction quantum yields. Additional enhancement of photostability can be achieved by aging of PVC or by flushing the sample with nitrogen, which confirms the involvement of oxygen in photodestruction. Different character of the time traces of the intensity of emission from single TDI molecules is observed for different polymer matrices, ranging from intense blinking in the least stable polycarbonate, to practically no blinking in the most stable PVC. These results suggest a photodegradation mechanism involving self-sensitized photooxidation in oxygen complexes of TDI. PMID- 26266723 TI - Electric-Field Tunable Band Offsets in Black Phosphorus and MoS2 van der Waals p n Heterostructure. AB - The structural and electronic properties of black phosphorus/MoS2 (BP/MoS2) van der Waals (vdW) heterostructure are investigated by first-principles calculations. It is demonstrated that the BP/MoS2 bilayer is a type-II p-n vdW heterostructure, and thus the lowest energy electron-hole pairs are spatially separated. The band gap of BP/MoS2 can be significantly modulated by external electric field, and a transition from semiconductor to metal is observed. It gets further support from the band edges of BP and MoS2 in BP/MoS2 bilayer, which show linear variations with E?. BP/MoS2 bilayer also exhibits modulation of its band offsets and band alignment by E?, resulting in different spatial distribution of the lowest energy electron-hole pairs. Our theoretical results may inspire much interest in experimental research of BP/MoS2 vdW heterostructures and would open a new avenue for application of the heterostructures in future nano- and optoelectronics. PMID- 26266724 TI - Modulating Exciton Dynamics in Composite Nanocrystals for Excitonic Solar Cells. AB - Quantum dots (QDs) represent one of the most promising materials for third generation solar cells due to their potential to boost the photoconversion efficiency beyond the Shockley-Queisser limit. Composite nanocrystals can challenge the current scenario by combining broad spectral response and tailored energy levels to favor charge extraction and reduce energy and charge recombination. We synthesized PbS/CdS QDs with different compositions at the surface of TiO2 nanoparticles assembled in a mesoporous film. The ultrafast photoinduced dynamics and the charge injection processes were investigated by pump-probe spectroscopy. We demonstrated good injection of photogenerated electrons from QDs to TiO2 in the PbS/CdS blend and used the QDs to fabricate solar cells. The fine-tuning of chemical composition and size of lead and cadmium chalcogenide QDs led to highly efficient PV devices (3% maximum photoconversion efficiency). This combined study paves the way to the full exploitation of QDs in next-generation photovoltaic (PV) devices. PMID- 26266725 TI - Ferroelectric Graphene-Perovskite Interfaces. AB - Owing to their record-breaking energy conversion efficiencies, hybrid organometallic perovskites have emerged as the most promising light absorbers and ambipolar carrier transporters for solution-processable solar cells. Simultaneously, due to its exceptional electron mobility, graphene represents a prominent candidate for replacing transparent conducting oxides. Thus, it is possible that combining these wonder materials may propel the efficiency toward the Schokley-Queisser limit. Here, using first-principles calculations on graphene-CH3NH3PbI3 interfaces, we find that graphene suppresses the octahedral tilt in the very first perovskite monolayer, leading to a nanoscale ferroelectric distortion with a permanent polarization of 3 mC/m(2). This interfacial ferroelectricity drives electron extraction from the perovskite and hinders electron-hole recombination by keeping the electrons and holes separated. The interfacial ferroelectricity identified here simply results from the interplay between graphene's planar structure and CH3NH3PbI3's octahedral connectivity; therefore, this mechanism may be effective in a much broader class of perovskites, with potential applications in photovoltaics and photocatalysis. PMID- 26266726 TI - Enhanced Carrier Lifetimes of Pure Iodide Hybrid Perovskite via Vapor Equilibrated Re-Growth (VERG). AB - Solution deposition of planar films of the hybrid perovskite (HP) methylammonium (MA) lead iodochloride (MAPbI3-xClx) often results in very low surface coverage, small grain size, and high density of defects, particularly for the pure iodide HP. These decrease the optoelectronic quality of MAPbI3 (minority lifetimes all less than 10 ns) and creates pinholes that may result in shunt pathways that severely degrade the efficiency of photovoltaic devices. The poor morphology is usually attributed to the formation of large disconnected grains of PbI2 that nucleate first and set the morphology of the final HP layer. As a result, many use PbCl2 as a lead source. The PbCl2 is less soluble, forms smaller grains, and promotes more continuous HP films. Here, we show a highly reproducible deposition method for pure iodide MAPbI3 that yields continuous films with large grain sizes and minority carrier lifetimes greater than 200 ns. The method consists of thermal evaporation of PbI2 and a post-deposition Vapor-Equilibrated Re-Growth (VERG) step at 110 degrees C in a closed vessel. PMID- 26266727 TI - Magnetic Particle Imaging Tracers: State-of-the-Art and Future Directions. AB - Magnetic particle imaging (MPI) is an emerging imaging modality with promising applications in diagnostic imaging and guided therapy. The image quality in MPI is strongly dependent on the nature of its iron oxide nanoparticle-based tracers. The selection of potential MPI tracers is currently limited, and the underlying physics of tracer response is not yet fully understood. An in-depth understanding of the magnetic relaxation processes that govern MPI tracers, gained through concerted theoretical and experimental work, is crucial to the development of optimized MPI tracers. Although tailored tracers will lead to improvements in image quality, tailored relaxation may also be exploited for biomedical applications or more flexible image contrast, as in the recent demonstration of color MPI. PMID- 26266728 TI - Interplay between Static and Dynamic Energy Transfer in Biofunctional Upconversion Nanoplatforms. AB - Clarification of the energy-transfer (ET) mechanism is of vital importance for constructing efficient upconversion nanoplatforms for biological/biomedical applications. Yet, most strategies of optimizing these nanoplatforms were casually based on a dynamic ET assumption. In this work, we have modeled quantitatively the shell-thickness-dependent interplay between dynamic and static ET in nanosystems and validated the model in a typical biofunctional upconversion nanoplatform composed of NaYF4:Er, Yb/NaYF4 upconversion nanoparticles (UCNPs), and energy-acceptor photosensitizing molecule Rose Bengal (RB). It was determined that with a proper thickness shell, the energy transferred via dynamic ET as well as static ET in this case could be significantly improved by ~4 and ~9 fold, respectively, compared with the total energy transferred from bare core UCNPs. Our results shall form the bedrock in designing highly efficient ET-based biofunctional nanoplatforms. PMID- 26266729 TI - Cryogenic Spectroscopy and Quantum Molecular Dynamics Determine the Structure of Cyclic Intermediates Involved in Peptide Sequence Scrambling. AB - Collision-induced dissociation (CID) is a key technique used in mass spectrometry based peptide sequencing. Collisionally activated peptides undergo statistical dissociation, forming a series of backbone fragment ions that reflect their amino acid (AA) sequence. Some of these fragments may experience a "head-to-tail" cyclization, which after proton migration, can lead to the cyclic structure opening in a different place than the initially formed bond. This process leads to AA sequence scrambling that may hinder sequencing of the initial peptide. Here we combine cryogenic ion spectroscopy and ab initio molecular dynamics simulations to isolate and characterize the precise structures of key intermediates in the scrambling process. The most stable peptide fragments show intriguing symmetric cyclic structures in which the proton is situated on a C2 symmetry axis and forms exceptionally short H-bonds (1.20 A) with two backbone oxygens. Other nonsymmetric cyclic structures also exist, one of which is protonated on the amide nitrogen, where ring opening is likely to occur. PMID- 26266730 TI - Nanotube-Enabled Vesicle-Vesicle Communication: A Computational Model. AB - Cell-to-cell communications via the tunneling nanotubes or gap junction channels are vital for the development and maintenance of multicellular organisms. Instead of these intrinsic communication pathways, how to design artificial communication channels between cells remains a challenging but interesting problem. Here, we perform dissipative particle dynamics (DPD) simulations to analyze the interaction between rotational nanotubes (RNTs) and vesicles so as to provide a novel design mechanism for cell-to-cell communication. Simulation results have demonstrated that the RNTs are capable of generating local disturbance and promote vesicle translocation toward the RNTs. Through ligand pattern designing on the RNTs, we can find a suitable nanotube candidate with a specific ligand coating pattern for forming the RNT-vesicle network. The results also show that a RNT can act as a bridged channel between vesicles, which facilitates substance transfer. Our findings provide useful guidelines for the molecular design of patterned RNTs for creating a synthetic channel between cells. PMID- 26266731 TI - CO2 Capture and Conversion on Rutile TiO2(110) in the Water Environment: Insight by First-Principles Calculations. AB - The conversion of CO2 by the virtue of sunlight has the great potential to produce useful fuels or valuable chemicals while decreasing CO2 emission from the traditional fossil fuels. Here, we use the first-principles calculations combined with the periodic continuum solvation model (PCSM) to explore the adsorption and reactivity of CO2 on rutile TiO2(110) in the water environment. The results exhibit that both adsorption structures and reactivity of CO2 are greatly affected by water coadsorption on rutile TiO2(110). In particular, the solvation effect can change the most stable adsorption configuration of CO2 and H2O on rutile TiO2(110). In addition, the detailed conversion mechanism of CO2 reduction is further explored in the water environment. The results reveal that the solvation effect cannot only greatly decrease the energy barrier of CO2 reduction but also affect the selectivity of the reaction processes. These results presented here show the importance of the aqueous solution, which should be helpful to understand the detailed reaction processes of photocatalysts. PMID- 26266733 TI - Photoexcited Carrier Dynamics of In2S3 Thin Films. AB - Indium sulfide (In2S3) is a promising absorber base for substitutionally doped intermediate band photovoltaics (IBPV); however, the dynamics of charge carriers traversing the electronic density of states that determine the optical and electronic response of thin films under stimuli have yet to be explored. The kinetics of photophysical processes in In2S3 grown by oxygen-free atomic layer deposition are deduced from photoconductivity, photoluminescence (PL), and transient absorption spectroscopy. We develop a map of excited-state dynamics for polycrystalline thin films including a secondary conduction band ~2.1 eV above the first, plus sulfur vacancy and indium interstitial defect levels resulting in long-lived (~100 ns) transients. Band-edge recombination produces PL and stimulated emission, which both intensify and red-shift as deposition temperature and grain size increase. The effect of rapid conduction band electron relaxation (<30 ps) and deep defect levels on IBPV employing In2S3-based absorbers is finally considered. PMID- 26266734 TI - Unusual Activity Trend for CO Oxidation on Pd(x)Au(140-x)@Pt Core@Shell Nanoparticle Electrocatalysts. AB - A theoretical and experimental study of the electrocatalytic oxidation of CO on PdxAu140-x@Pt dendrimer-encapsulated nanoparticle (DEN) catalysts is presented. These nanoparticles are comprised of a core having an average of 140 atoms and a Pt monolayer shell. The CO oxidation activity trend exhibits an unusual koppa shape as the number of Pd atoms in the core is varied from 0 to 140. Calculations based on density functional theory suggest that the koppa-shaped trend is driven primarily by structural changes that affect the CO binding energy on the surface. Specifically, a pure Au core leads to deformation of the Pt shell and a compression of the Pt lattice. In contrast, Pd, from the pure Pd cores, tends to segregate on the DEN surface, forming an inverted configuration having Pt within the core and Pd in the shell. With a small addition of Au, however, the alloy PdAu cores stabilize the core@shell structures by preventing Au and Pd from escaping to the particle surface. PMID- 26266732 TI - Biomolecular Crowding Arising from Small Molecules, Molecular Constraints, Surface Packing, and Nano-Confinement. AB - The effect of macromolecular crowding on the structure, dynamics, and reactivity of biomolecules is well established and the relevant research has been extensively reviewed. Herein, we focus our discussion on crowding effects arising from small cosolvent molecules and densely packed surface conditions. In addition, we highlight recent efforts that capitalize on the excluded volume effect for various tailored biochemical and biophysical applications. Specifically, we discuss how a targeted increase in local mass density can be exploited to gain insight into the folding dynamics of the protein of interest and how confinement via reverse micelles can be used to study a range of biophysical questions, from protein hydration dynamics to amyloid formation. PMID- 26266735 TI - Examining Substrate-Induced Plasmon Mode Splitting and Localization in Truncated Silver Nanospheres with Electron Energy Loss Spectroscopy. AB - Motivated by the need to study the size dependence of nanoparticle-substrate systems, we present a combined experimental and theoretical electron energy loss spectroscopy (EELS) study of the plasmonic spectrum of substrate-supported truncated silver nanospheres. This work spans the entire classical range of plasmonic behavior probing particles of 20-1000 nm in diameter, allowing us to map the evolution of localized surface plasmons into surface plasmon polaritons and study the size dependence of substrate-induced mode splitting. This work constitutes the first nanoscopic characterization and imaging of these effects in truncated nanospheres, setting the stage for the systematic study of plasmon mediated energy transfer in nanoparticle-substrate systems. PMID- 26266736 TI - Salt-Induced Universal Slowing Down of the Short-Time Self-Diffusion of a Globular Protein in Aqueous Solution. AB - The short-time self-diffusion D of the globular model protein bovine serum albumin in aqueous (D2O) solutions has been measured comprehensively as a function of the protein and trivalent salt (YCl3) concentration, noted cp and cs, respectively. We observe that D follows a universal master curve D(cs,cp) = D(cs = 0,cp) g(cs/cp), where D(cs = 0,cp) is the diffusion coefficient in the absence of salt and g(cs/cp) is a scalar function solely depending on the ratio of the salt and protein concentration. This observation is consistent with a universal scaling of the bonding probability in a picture of cluster formation of patchy particles. The finding corroborates the predictive power of the description of proteins as colloids with distinct attractive ion-activated surface patches. PMID- 26266737 TI - Electrostatic Interactions Influence Protein Adsorption (but Not Desorption) at the Silica-Aqueous Interface. AB - High-throughput single-molecule total internal reflection fluorescence microscopy was used to investigate the effects of pH and ionic strength on bovine serum albumin (BSA) adsorption, desorption, and interfacial diffusion at the aqueous fused silica interface. At high pH and low ionic strength, negatively charged BSA adsorbed slowly to the negatively charged fused silica surface. At low pH and low ionic strength, where BSA was positively charged, or in solutions at higher ionic strength, adsorption was approximately 1000 times faster. Interestingly, neither surface residence times nor the interfacial diffusion coefficients of BSA were influenced by pH or ionic strength. These findings suggested that adsorption kinetics were dominated by energy barriers associated with electrostatic interactions, but once adsorbed, protein-surface interactions were dominated by short-range nonelectrostatic interactions. These results highlight the ability of single-molecule techniques to isolate elementary processes (e.g., adsorption and desorption) under steady-state conditions, which would be impossible to measure using ensemble-averaging methods. PMID- 26266738 TI - Ten Reasons Why Peer Review Makes Sense. PMID- 26266739 TI - Controlling Charge Carrier Overlap in Type-II ZnSe/ZnS/CdS Core-Barrier-Shell Quantum Dots. AB - We describe the synthesis and spectroscopic characterization of colloidal ZnSe/ZnS/CdS nanocrystals, which exhibit a type-II electronic structure and wave function overlap that is strongly dependent on the thickness of the ZnS barrier. Barrier thickness is controlled by both the amount of deposited material and the reaction and annealing temperature of CdS shell growth. The results show that a single monolayer of ZnS mitigates the overlap significantly, while four and more monolayers effectively suppress band edge absorption and emission. Transient absorption spectra reveal a broad distribution of excitons with mixed S and P symmetry, which become allowed due to alloy formation and contribute to charge carrier relaxation across the barrier. We present a model of the core/shell interface based on cation diffusion, which allows one to estimate the extent of the diffusion layer from optical spectra. PMID- 26266740 TI - Genesis of Delaminated-Zeolite Morphology: 3-D Characterization of Changes by STEM Tomography. AB - Zeolite delamination increases the external surface area available for catalyzing the conversion of bulky molecules, but a fundamental understanding of the delamination process remains unknown. Here we report morphological changes accompanying delamination on the length scale of individual zeolite clusters determined by 3-D imaging in scanning transmission electron microscopy. The results are tomograms that demonstrate delamination as it proceeds on the nanoscale through two distinct key steps: a chemical treatment that leads to a swelled material and a subsequent calcination that leads to curling and peeling off of delaminated zeolite sheets over hundreds of nanometers. These results characterize the direct, local, 3-D morphological changes accompanying delaminated materials synthesis and, with corroboration by mercury porosimetry, provide unique insight into the morphology of these materials, which is difficult to obtain with any other technique. PMID- 26266741 TI - Impact of Ga-V Codoping on Interfacial Electron Transfer in Dye-Sensitized TiO2. AB - The improvement of charge transfer between an organic molecule and a semiconductor is an important and challenging goal in the fields of photovoltaics and photocatalysis. In this work, we present a time-dependent density functional theory investigation of the impact of Ga-V codoping of TiO2 on the excited-state electron injection from perylene-3-carboxylic acid. The doping is shown to raise the charge-transfer efficiency for the highest possible surface dye uptake by ~16%. The strength of the effect depends on the dopant-pair-dye separation, dopant concentration, and distribution of Ga, V atoms in TiO2. The doping of the superficial level turns out to be more favorable than those in the bulk. The changes in electron injection dynamics are attributed to the modification of accepting semiconductor levels and hybridization profile between molecular and semiconductor states. PMID- 26266742 TI - Structural Evidence of Amyloid Fibril Formation in the Putative Aggregation Domain of TDP-43. AB - TDP-43 can form pathological proteinaceous aggregates linked to ALS and FTLD. Within the putative aggregation domain, engineered repeats of residues 341-366 can recruit endogenous TDP-43 into aggregates inside cells; however, the nature of these aggregates is a debatable issue. Recently, we showed that a coil to beta hairpin transition in a short peptide corresponding to TDP-43 residues 341-357 enables oligomerization. Here we provide definitive structural evidence for amyloid formation upon extensive characterization of TDP-43(341-357) via chromophore and antibody binding, electron microscopy (EM), solid-state NMR, and X-ray diffraction. On the basis of these findings, structural models for TDP 43(341-357) oligomers were constructed, refined, verified, and analyzed using docking, molecular dynamics, and semiempirical quantum mechanics methods. Interestingly, TDP-43(341-357) beta-hairpins assemble into a novel parallel beta turn configuration showing cross-beta spine, cooperative H-bonding, and tight side-chain packing. These results expand the amyloid foldome and could guide the development of future therapeutics to prevent this structural conversion. PMID- 26266743 TI - First-Principles Investigation of Nanopore Sequencing Using Variable Voltage Bias on Graphene-Based Nanoribbons. AB - In this study, we examine the mechanism of nanopore-based DNA sequencing using a voltage bias across a graphene nanoribbon. Using density function theory and a nonequilibrium Green's function approach, we determine the transmission spectra and current profile for adenine, guanine, cytosine, thymine, and uracil as a function of bias voltage in an energy minimized configuration. Utilizing the transmission current, we provide a general methodology for the development of a three nanopore graphene-based device that can be used to distinguish between the various nucleobases for DNA/RNA sequencing. From our analysis, we deduce that it is possible to use different transverse currents across a multinanopore device to differentiate between nucleobases using various voltages of 0.5, 1.3, and 1.6 V. Overall, our goal is to improve nanopore design to further DNA/RNA nucleobase sequencing and biomolecule identification techniques. PMID- 26266744 TI - Large-Size CH3NH3PbBr3 Single Crystal: Growth and In Situ Characterization of the Photophysics Properties. AB - We reported a facile single-solution fabrication method to grow large-scale CH3NH3PbBr3 hybrid perovskite single crystal at room temperature. The obtained single crystal in this experiment was 14 * 14 mm. The sample's in situ photophysics properties under dark and illumination, including the surface morphology, work function, surface current distribution, microcosmic I-V curves, as well as the polarization behavior, were in situ characterized by integrated utilization of a scanning probe microscopy, respectively. Piezoresponse force microscopy (PFM) phase angles indicated the existence of "polarization" in CH3NH3PbBr3 lattice. Interestingly, the "polarization effect" was enhanced by the plus light source. Moreover, a surface potential shift as large as 200 mV was observed under the condition of the illumination on and off. This research is proposed to provide an opportunity to take a fresh look at the architectural design and photovoltaic performance origin of the hybrid perovskite solar cells. PMID- 26266745 TI - Non-Contact Local Conductance Mapping of Individual Graphene Oxide Sheets during the Reduction Process. AB - We used electrostatic force microscopy (EFM) to investigate local conducting states of atomically thin individual graphene oxide (GO) sheets and monitor the spatial evolution of their conducting properties during the reduction process. Because of the thinness of the GO sheets and finite carrier density, the electric field is partially screened in the reduced GO, which is manifested in the EFM phase signals. We found inhomogeneous oxidation states in as-prepared GO sheets and followed the evolution of reduction process in the individual GO sheets during both thermal and chemical reduction. We also compared the EFM measurement results with simultaneous IV characteristics to assess correlations between two measurements. PMID- 26266746 TI - Rate-Dependent Nucleation and Growth of NaO2 in Na-O2 Batteries. AB - Understanding the oxygen reduction reaction kinetics in the presence of Na ions and the formation mechanism of discharge product(s) is key to enhancing Na-O2 battery performance. Here we show NaO2 as the only discharge product from Na-O2 cells with carbon nanotubes in 1,2-dimethoxyethane from X-ray diffraction and Raman spectroscopy. Sodium peroxide dihydrate was not detected in the discharged electrode with up to 6000 ppm of H2O added to the electrolyte, but it was detected with ambient air exposure. In addition, we show that the sizes and distributions of NaO2 can be highly dependent on the discharge rate, and we discuss the formation mechanisms responsible for this rate dependence. Micron sized (~500 nm) and nanometer-scale (~50 nm) cubes were found on the top and bottom of a carbon nanotube (CNT) carpet electrode and along CNT sidewalls at 10 mA/g, while only micron-scale cubes (~2 MUm) were found on the top and bottom of the CNT carpet at 1000 mA/g, respectively. PMID- 26266747 TI - Anomalous Capacitance Maximum of the Glassy Carbon-Ionic Liquid Interface through Dilution with Organic Solvents. AB - We use electrochemical impedance spectroscopy to measure the effect of diluting a hydrophobic room temperature ionic liquid with miscible organic solvents on the differential capacitance of the glassy carbon-electrolyte interface. We show that the minimum differential capacitance increases with dilution and reaches a maximum value at ionic liquid contents near 5-10 mol% (i.e., ~1 M). We provide evidence that mixtures with 1,2-dichloroethane, a low-dielectric constant solvent, yield the largest gains in capacitance near the open circuit potential when compared against two traditional solvents, acetonitrile and propylene carbonate. To provide a fundamental basis for these observations, we use a coarse grained model to relate structural variations at the double layer to the occurrence of the maximum. Our results reveal the potential for the enhancement of double-layer capacitance through dilution. PMID- 26266748 TI - Ultrafast Exciton Dynamics in InGaN/GaN and Rh/Cr2O3 Nanoparticle-Decorated InGaN/GaN Nanowires. AB - Ultrafast exciton and charge-carrier dynamics in InGaN/GaN nanowires (NWs) with and without Rh/Cr2O3 nanoparticle (NP) decoration have been investigated using femtosecond transient absorption (TA) techniques with excitation at 415 nm and white-light probe (450-700 nm). By comparing the TA profiles between InGaN/GaN and InGaN/GaN-Rh/Cr2O3 NWs, an additional decay component on the medium time scale (~50 ps) was identified with Rh/Cr2O3 decoration, which is attributed to interfacial charge transfer from InGaN/GaN NWs to Rh/Cr2O3 NPs, desired for light energy conversion applications. This is consistent with reduced photoluminescence (PL) of the NWs by the Rh/Cr2O3 NPs. A kinetic model was developed to explain the TA results and gain further insight into the exciton and charge-carrier dynamics. PMID- 26266749 TI - Reagent-free and portable detection of Bacillus anthracis spores using a microfluidic incubator and smartphone microscope. AB - Bacillus anthracis is the causative agent of anthrax and can be contracted by humans and herbivorous mammals by inhalation, ingestion, or cutaneous exposure to bacterial spores. Due to its stability and disease potential, B. anthracis is a recognized biothreat agent and robust detection and viability methods are needed to identify spores from unknown samples. Here we report the use of smartphone based microscopy (SPM) in combination with a simple microfluidic incubation device (MID) to detect 50 to 5000 B. anthracis Sterne spores in 3 to 5 hours. This technique relies on optical monitoring of the conversion of the ~1 MUm spores to the filamentous vegetative cells that range from tens to hundreds of micrometers in length. This distinguishing filament formation is unique to B. anthracis as compared to other members of the Bacillus cereus group. A unique feature of this approach is that the sample integrity is maintained, and the vegetative biomass can be removed from the chip for secondary molecular analysis such as PCR. Compared with existing chip-based and rapid viability PCR methods, this new approach reduces assay time by almost half, and is highly sensitive, specific, and cost effective. PMID- 26266750 TI - Characterization and cross-protection evaluation of M949_1603 gene deletion Riemerella anatipestifer mutant RA-M1. AB - Riemerella anatipestifer infection causes high mortality for ducks which results in major economic losses in the duck industry. In this study, we identified a mutant strain RA-M1 by Tn4351 transposon mutagenesis, in which the M949_1603 gene encoding glycosyl transferase was inactivated. PCR analysis revealed that M949_1603 gene is specifically existed in R. anatipestifer serotype 1 strains. RA M1 presented no reactivity to the anti-lipopolysaccharide (LPS) MAb in an indirect ELISA. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) followed by Western blotting demonstrated that RA-M1 LPS had a deficiency in ladder-like binding pattern to rabbit antiserum against R. anatipestifer serotype 1 strain CH3, indicating that the O-antigen structure of RA-M1 was changed. RA-M1 showed significant attenuated virulence in ducks and higher sensitivity to normal duck serum, compared with its parent strain CH3. Furthermore, cross-protection of RA-M1 for R. anatipestifer serotypes 1, 2, and 10 strains was evaluated. Ducks that received two immunizations with inactivated RA-M1 vaccine were 100% protected from challenge with R. anatipestifer serotype 1 strain WJ4, serotype 2 strain Yb2, and serotype 10 strain HXb2. No changes were observed in the liver, heart, or spleen samples from the protected ducks during autopsy and histological examination. Furthermore, vaccination generated high antibody titers of 1:12,800 against serotypes 1, 2, and 10 strains and enhanced production of interleukin 2 (IL-2) and IL-4 in ducks. These results suggested that M949_1603 gene is associated with serotype 1 O-antigen biosynthesis, and mutant RA-M1 could be used as a novel cross-protection vaccine candidate to protect ducks against R. anatipestifer infection. PMID- 26266751 TI - Diversity of hydrolases from hydrothermal vent sediments of the Levante Bay, Vulcano Island (Aeolian archipelago) identified by activity-based metagenomics and biochemical characterization of new esterases and an arabinopyranosidase. AB - A metagenomic fosmid expression library established from environmental DNA (eDNA) from the shallow hot vent sediment sample collected from the Levante Bay, Vulcano Island (Aeolian archipelago) was established in Escherichia coli. Using activity based screening assays, we have assessed 9600 fosmid clones corresponding to approximately 350 Mbp of the cloned eDNA, for the lipases/esterases/lactamases, haloalkane and haloacid dehalogenases, and glycoside hydrolases. Thirty-four positive fosmid clones were selected from the total of 120 positive hits and sequenced to yield ca. 1360 kbp of high-quality assemblies. Fosmid inserts were attributed to the members of ten bacterial phyla, including Proteobacteria, Bacteroidetes, Acidobateria, Firmicutes, Verrucomicrobia, Chloroflexi, Spirochaetes, Thermotogae, Armatimonadetes, and Planctomycetes. Of ca. 200 proteins with high biotechnological potential identified therein, we have characterized in detail three distinct alpha/beta-hydrolases (LIPESV12_9, LIPESV12_24, LIPESV12_26) and one new alpha-arabinopyranosidase (GLV12_5). All LIPESV12 enzymes revealed distinct substrate specificities tested against 43 structurally diverse esters and 4 p-nitrophenol carboxyl esters. Of 16 different glycosides tested, the GLV12_5 hydrolysed only p-nitrophenol-alpha-(L) arabinopyranose with a high specific activity of about 2.7 kU/mg protein. Most of the alpha/beta-hydrolases were thermophilic and revealed a high tolerance to, and high activities in the presence of, numerous heavy metal ions. Among them, the LIPESV12_24 was the best temperature-adapted, retaining its activity after 40 min of incubation at 90 degrees C. Furthermore, enzymes were active in organic solvents (e.g., >30% methanol). Both LIPESV12_24 and LIPESV12_26 had the GXSXG pentapeptides and the catalytic triads Ser-Asp-His typical to the representatives of carboxylesterases of EC 3.1.1.1. PMID- 26266752 TI - The complicated substrates enhance the microbial diversity and zinc leaching efficiency in sphalerite bioleaching system. AB - This study used an artificial enrichment microbial consortium to examine the effects of different substrate conditions on microbial diversity, composition, and function (e.g., zinc leaching efficiency) through adding pyrite (SP group), chalcopyrite (SC group), or both (SPC group) in sphalerite bioleaching systems. 16S rRNA gene sequencing analysis showed that microbial community structures and compositions dramatically changed with additions of pyrite or chalcopyrite during the sphalerite bioleaching process. Shannon diversity index showed a significantly increase in the SP (1.460), SC (1.476), and SPC (1.341) groups compared with control (sphalerite group, 0.624) on day 30, meanwhile, zinc leaching efficiencies were enhanced by about 13.4, 2.9, and 13.2%, respectively. Also, additions of pyrite or chalcopyrite could increase electric potential (ORP) and the concentrations of Fe3+ and H+, which were the main factors shaping microbial community structures by Mantel test analysis. Linear regression analysis showed that ORP, Fe3+ concentration, and pH were significantly correlated to zinc leaching efficiency and microbial diversity. In addition, we found that leaching efficiency showed a positive and significant relationship with microbial diversity. In conclusion, our results showed that the complicated substrates could significantly enhance microbial diversity and activity of function. PMID- 26266753 TI - Proteomic insights into metabolic adaptation to deletion of metE in Saccharopolyspora spinosa. AB - Saccharopolyspora spinosa can produce spinosad as a major secondary metabolite, which is an environmentally friendly agent for insect control. Cobalamin independent methionine synthase (MetE) is an important enzyme in methionine biosynthesis, and this enzyme is probably closely related to spinosad production. In this study, its corresponding gene metE was inactivated, which resulted in a rapid growth and glucose utilisation rate and almost loss of spinosad production. A label-free quantitative proteomics-based approach was employed to obtain insights into the mechanism by which the metabolic network adapts to the absence of MetE. A total of 1440 proteins were detected from wild-type and DeltametE mutant strains at three time points: stationary phase of DeltametE mutant strain (S1DeltametE , 67 h), first stationary phase of wild-type strain (S1WT, 67 h) and second stationary phase of wild-type strain (S2WT, 100 h). Protein expression patterns were determined using an exponentially modified protein abundance index (emPAI) and analysed by comparing S1DeltametE /S1WT and S1DeltametE /S2WT. Results showed that differentially expressed enzymes were mainly involved in primary metabolism and genetic information processing. This study demonstrated that the role of MetE is not restricted to methionine biosynthesis but rather is involved in global metabolic regulation in S. spinosa. PMID- 26266754 TI - Improvement in the thermostability of a type A feruloyl esterase, AuFaeA, from Aspergillus usamii by iterative saturation mutagenesis. AB - Feruloyl or ferulic acid esterase (Fae, EC 3.1.1.73) catalyzes the hydrolysis of ester bonds between polysaccharides and phenolic acid compounds in xylan side chain. In this study, the thermostability of a type A feruloyl esterase (AuFaeA) from Aspergillus usamii was increased by iterative saturation mutagenesis (ISM). Two amino acids, Ser33 and Asn92, were selected for saturation mutagenesis according to the B-factors analyzed by B-FITTER software and DeltaDeltaG values predicted by PoPMuSiC algorithm. After screening the saturation mutagenesis libraries constructed in Pichia pastoris, 15 promising variants were obtained. The best variant S33E/N92-4 (S33E/N92R) produced a T m value of 44.5 degrees C, the half-lives (t1/2) of 35 and 198 min at 55 and 50 degrees C, respectively, corresponding to a 4.7 degrees C, 2.33- and 3.96-fold improvement compared to the wild type. Additionally, the best S33 variant S33-6 (S33E) was thermostable at 50 degrees C with a t1/2 of 82 min, which was 32 min longer than that of the wild type. All the screened S33E/N92 variants were more thermostable than the best S33 variant S33-6 (S33E). This work would contribute to the further studies on higher thermostability modification of type A feruloyl esterases, especially those from fungi. The thermostable feruloyl esterase variants were expected to be potential candidates for industrial application in prompting the enzymic degradation of plant biomass materials at elevated temperatures. PMID- 26266755 TI - Photosynthetic aeration in biological wastewater treatment using immobilized microalgae-bacteria symbiosis. AB - Chlorella vulgaris encapsulated in alginate beads were added into a bioreactor treating synthetic wastewater using Pseudomonas putida. A symbiotic CO2/O2 gas exchange was established between the two microorganisms for photosynthetic aeration of wastewater. During batch operation, glucose removal efficiency in the bioreactor improved from 50% in 12 h without aeration to 100% in 6 h, when the bioreactor was aerated photosynthetically. During continuous operation, the bioreactor was operated at a low hydraulic retention time of 3.3 h at feed concentrations of 250 and 500 mg/L glucose. The removal efficiency at 500 mg/L increased from 73% without aeration to 100% in the presence of immobilized microalgae. The initial microalgae concentration was critical to achieve adequate aeration, and the removal rate increased with increasing microalgae concentration. The highest removal rate of 142 mg/L-h glucose was achieved at an initial microalgae concentration of 190 mg/L. Quantification of microalgae growth in the alginate beads indicated an exponential growth during symbiosis, indicating that the bioreactor performance was limited by oxygen production rates. Under symbiotic conditions, the chlorophyll content of the immobilized microalgae increased by more than 30%. These results indicate that immobilized microalgae in symbiosis with heterotrophic bacteria are promising in wastewater aeration. PMID- 26266756 TI - Growth in children with choledochal malformations: effect of the Roux loop. AB - PURPOSE: Excision and biliary reconstruction using a Roux loop is the current standard for choledochal malformation (CM). This is un-physiological, delivering bile beyond the duodenum and excluding a significant length of the jejunum from intestinal absorption. We investigated whether this had an effect on post operative growth. METHODS: Retrospective case-note analysis of children surgically treated for CM. Growth variables were converted to standard deviation scores (SDS) and compared against population norms. P < 0.05 was significant. RESULTS: From 1994 to 2014, 135 children (<16 years) were identified. Median age at surgery was 3.3 (IQR 1.5-7) years. Morphology included: type 1 Cystic (n = 54, 40%), type 1 Fusiform (n = 58, 43%) and type 4 (intra and extra-hepatic) (n = 22, 16%). There was pre-operative growth failure [median weight SDS = -0.4 (-1.2 - 0.4), P = 0.0004] with a similar trend for height [SDS = -0.38 (-1.2 - 0.5), P = 0.08)]. This correlated with presentation bilirubin (r s = -0.24, P = 0.004), GGT (r s = -0.27, P = 0.002) and AST (r s = -0.27, P = 0.002) but not morphology (P = 0.82) or presentation (P = 0.4). Median follow-up was 1.9 (0.6-4.7) years, during which time both height (P = 0.73) and weight (P = 0.45) reverted to normal. CONCLUSION: This is the first report of growth in children with CM following a Roux-loop reconstruction and showed pre-operative growth failure probably attributed to a period of biliary obstruction but catch-up growth when corrected. PMID- 26266757 TI - The Hot and the Cold: Radiofrequency Versus Cryoballoon Ablation for Atrial Fibrillation. AB - Catheter ablation is superior to antiarrhythmic drugs in maintaining sinus rhythm for patients with atrial fibrillation (AF). Pulmonary vein (PV) isolation is the cornerstone of any AF ablation procedure. Conventionally, this is achieved by performing point by point lesions using radiofrequency (RF) energy. However, this is technically challenging, time consuming and is associated with a number of complications. Long-term durability of PV isolation is also a concern. To address these issues, 'one-shot' energy delivery systems and alternative energy sources have been developed. The cryoballoon system has emerged as the most commonly used alternative to point by point RF technology. In this paper, we compare the technology, biophysics and clinical data of cryoballoon to conventional RF ablation for AF. The safety and efficacy of cryoballoon compared to RF ablation is critically reviewed. We conclude by looking at future applications of this technology. PMID- 26266759 TI - Amplification of mutated NRAS leading to congenital melanoma in neurocutaneous melanocytosis. AB - The mechanisms behind malignant progression in patients with giant nevi are largely unknown. Here, we aim to describe novel genetic findings and explain possible mechanisms resulting in the most severe form of neurocutaneous melanocytosis. Detailed histological (biopsy and post-mortem) studies, tissue culture, and high-resolution cytogenetic analysis, including chromosome and array comparative genomic hybridization, Ion AmpliSeq Cancer Panel, and Sanger sequencing, were performed on tissues from a white male who succumbed at 17 months of age to congenital melanoma associated with a bathing-trunk nevus. We also used quantitative PCR to quantitatively assess the expression of NRAS among normal cells, including fibroblast and melanocytes, as well as melanoma cells from our patient. Full autopsy documented tumors in the brain, spinal cord, lung, liver, testis, bone marrow, and, retrospectively, in the placenta. Next generation sequencing and chromosome microarray in our patient revealed novel findings, including duplication of a mutated NRAS gene, leading to an aggressive clinical course and disseminated disease. Quantitative PCR showed a five-fold increase in NRAS expression in the melanoma cell line when compared with normal melanocytes. Finally, three amino acid-changing germline variants were detected: homozygous TP53 p.P72R, heterozygous KIT p.M541L, and homozygous KDR (VEGFR2) p.Q472H. These genes are involved in malignancy and other potentially relevant pathways, such as mast cell and melanocytic signaling, as well as angiogenesis. These findings provide novel insights into the biology of congenital melanocytic proliferations, showing that amplification of mutated NRAS seems to represent a new genetic mechanism leading to melanoma in the context of neurocutaneous melanocytosis. PMID- 26266760 TI - Single cell metastatic phenotyping using pulsed nanomechanical indentations. AB - The existing approach to characterize cell biomechanical properties typically utilizes switch-like models of mechanotransduction in which cell responses are analyzed in response to a single nanomechanical indentation or a transient pulsed stress. Although this approach provides effective descriptors at population level, at a single-cell-level, there are significant overlaps in the biomechanical descriptors of non-metastatic and metastatic cells which precludes the use of biomechanical markers for single cell metastatic phenotyping. This study presents a new promising marker for biosensing metastatic and non metastatic cells at a single-cell-level using the effects of a dynamic microenvironment on the biomechanical properties of cells. Two non-metastatic and two metastatic epithelial breast cell lines are subjected to a pulsed stresses regimen exerted by atomic force microscopy. The force-time data obtained for the cells revealed that the non-metastatic cells increase their resistance against deformation and become more stiffened when subjected to a series of nanomechanical indentations. On the other hand, metastatic cells become slightly softened when their mechanical microenvironment is subjected to a similar dynamical changes. This distinct behavior of the non-metastatic and metastatic cells to the pulsed stresses paradigm provided a signature for single-cell-level metastatic phenotyping with a high confidence level of ~95%. PMID- 26266758 TI - The Concept of Qailulah (Midday Napping) from Neuroscientific and Islamic Perspectives. AB - Napping/siesta during the day is a phenomenon, which is widely practised in the world. However, the timing, frequency, and duration may vary. The basis of napping is also diverse, but it is mainly done for improvement in alertness and general well-being. Neuroscience reveals that midday napping improves memory, enhances alertness, boosts wakefulness and performance, and recovers certain qualities of lost night sleep. Interestingly, Islam, the religion of the Muslims, advocates midday napping primarily because it was a practice preferred by Prophet Muhammad (pbuh). The objectives of this review were to investigate and compare identical key points on focused topic from both neuroscientific and Islamic perspectives and make recommendations for future researches. PMID- 26266761 TI - Optical filter selection for high confidence discrimination of strongly overlapping infrared chemical spectra. AB - Optical filter-based chemical sensing techniques provide a new avenue to develop low-cost infrared sensors. These methods utilize multiple infrared optical filters to selectively measure different response functions for various chemicals, dependent on each chemical's infrared absorption. Rather than identifying distinct spectral features, which can then be used to determine the identity of a target chemical, optical filter-based approaches rely on measuring differences in the ensemble response between a given filter set and specific chemicals of interest. Therefore, the results of such methods are highly dependent on the original optical filter choice, which will dictate the selectivity, sensitivity, and stability of any filter-based sensing method. Recently, a method has been developed that utilizes unique detection vector operations defined by optical multifilter responses, to discriminate between volatile chemical vapors. This method, comparative-discrimination spectral detection (CDSD), is a technique which employs broadband optical filters to selectively discriminate between chemicals with highly overlapping infrared absorption spectra. CDSD has been shown to correctly distinguish between similar chemicals in the carbon-hydrogen stretch region of the infrared absorption spectra from 2800-3100 cm(-1). A key challenge to this approach is how to determine which optical filter sets should be utilized to achieve the greatest discrimination between target chemicals. Previous studies used empirical approaches to select the optical filter set; however this is insufficient to determine the optimum selectivity between strongly overlapping chemical spectra. Here we present a numerical approach to systematically study the effects of filter positioning and bandwidth on a number of three-chemical systems. We describe how both the filter properties, as well as the chemicals in each set, affect the CDSD results and subsequent discrimination. These results demonstrate the importance of choosing the proper filter set and chemicals for comparative discrimination, in order to identify the target chemical of interest in the presence of closely matched chemical interferents. These findings are an integral step in the development of experimental prototype sensors, which will utilize CDSD. PMID- 26266762 TI - Transoral robotic surgery (TORS) for laryngeal and hypopharyngeal cancers. AB - Transoral robotic surgery (TORS) is increasingly used in laryngeal/hypopharyngeal cancer surgery. Ablative procedures described in these anatomical sites include: (i) supraglottic laryngectomy, (ii) total laryngectomy, (iii) glottic cordectomy, and (iv) partial pharyngectomy. TORS supraglottic laryngectomy remains the most commonly performed of these procedures. Initial oncologic and functional outcomes with these procedures are promising and comparable to other treatment options. As robotic instrumentation technology advances a rise in TORS laryngeal/hypopharyngeal surgery is anticipated. PMID- 26266764 TI - Tomographic reconstruction of ionospheric electron density during the storm of 5 6 August 2011 using multi-source data. AB - The insufficiency of data is the essential reason for ill-posed problem existed in computerized ionospheric tomography (CIT) technique. Therefore, the method of integrating multi-source data is proposed. Currently, the multiple satellite navigation systems and various ionospheric observing instruments provide abundant data which can be employed to reconstruct ionospheric electron density (IED). In order to improve the vertical resolution of IED, we do research on IED reconstruction by integration of ground-based GPS data, occultation data from the LEO satellite, satellite altimetry data from Jason-1 and Jason-2 and ionosonde data. We used the CIT results to compare with incoherent scatter radar (ISR) observations, and found that the multi-source data fusion was effective and reliable to reconstruct electron density, showing its superiority than CIT with GPS data alone. PMID- 26266763 TI - Angiopoietin-1 improves endothelial progenitor cell-dependent neovascularization in diabetic wounds. AB - BACKGROUND: The diabetic phenotype of wound healing is in part characterized by impaired neovascularization and deficient endothelial progenitor cell (EPC) recruitment. Angiopoietin-1 (Ang-1) is a potent mobilizer of EPCs from the bone marrow (BM). A suggested mechanism for EPC mobilization from the BM is mediated by matrix metalloproteinase 9 (MMP-9) and stem cell factor (SCF). Taken together, we hypothesized that overexpression of Ang-1 in diabetic wounds will recruit EPCs and improve neovascularization and wound healing. METHODS: An endothelial lineage BM-labeled murine model of diabetes was developed to track BM-derived EPCs. FVBN mice were lethally irradiated and then reconstituted with BM from syngeneic Tie2/LacZ donor mice. Diabetes was induced with streptozotocin. Dorsal wounds in BM-transplanted mice were treated with Ad-Ang-1, Ad-GFP, or phosphate-buffered saline. At day 7 after injury, wounds were harvested and analyzed. A similar experiment was conducted in EPC mobilization deficient MMP-9 -/- mice to determine whether the effects of Ang-1 were EPC-dependent. RESULTS: Overexpression of Ang-1 resulted in greatly improved re-epithelialization, neovascularization, and EPC recruitment in diabetic BM-transplanted wounds at day 7. Ang-1 treatment resulted in increased serum levels of proMMP-9 and SCF but had no effect on vascular endothelial growth factor levels. According to our FACS results, peripheral blood EPC (CD34(+)/Cd133(+)/Flk1(+)) counts at day 3 after wounding showed impaired EPC mobilization in MMP-9 -/- mice compared with those of wild-type controls. EPC mobilization was rescued by SCF administration, validating this model for EPC-mobilization-deficient mechanistic studies. In MMP 9 -/- mice, Ad-Ang-1 accelerated re-epithelialization in a similar manner, but had no effect on neovascularization. CONCLUSION: Our results show that Ang-1 administration results in improved neovascularization which is dependent on EPC recruitment and has direct effects on wound re-epithelialization. These data may represent a novel strategy to correct the phenotype of impaired diabetic neovascularization and may improve diabetic wound healing. PMID- 26266765 TI - Metformin and epithelial ovarian cancer therapeutics. AB - BACKGROUND: Ovarian cancer is one of the most common lethal gynecological malignancies world-wide. Despite an initial 70-80% response rate, most patients relapse within 1-2 years and develop chemo-resistance. Hence, the identification of novel drugs or the repositioning of known drugs to re-sensitize ovarian cancer cells to existing chemotherapy regimens is needed. Here, we evaluated the effect of metformin (an anti-diabetic drug) on ovarian cancer cells, based on its putative effect on other solid tumors. METHODS: Primary cultures of epithelial ovarian cancer cells established from ascitic fluids of untreated ovarian cancer patients and the SKOV-3 ovarian cancer-derived cell line were used. The respective cells were treated with metformin, carboplatin and paclitaxel alone and its various combinations and their effects, including the ability to induce apoptosis, were examined. Concomitantly, the cells were assessed for the expression of several apoptosis-related mRNAs and proteins using quantitative real time PCR, flowcytometry and Western blotting. RESULTS: We found that metformin induced apoptosis in the ovarian cancer cells tested, and provoked a cell cycle arrest in the G0/G1 and S-phase. Metformin induced apoptosis by down regulating Bcl-2 and Bcl-xL expression, and up-regulating Bax and Cytochrome c expression. We also found that the apoptosis induction by metformin could be enhanced by a combinatorial use of carboplatin and/or paclitaxel. CONCLUSIONS: Our data indicate that metformin can induce apoptosis in both primary ovarian cancer cells and in SKOV-3 cells. When metformin was combined with carboplatin or paclitaxel, an increased apoptotic activity was observed, implicating a chemo adjuvant potential. PMID- 26266766 TI - Prospective study of cyclophosphamide, thiotepa, carboplatin combined with adoptive DC-CIK followed by metronomic cyclophosphamide therapy as salvage treatment for triple negative metastatic breast cancers patients (aged <45). AB - BACKGROUND: The recent immunotherapy treatment on triple-negative breast cancer (TNBC) leads to the breakthrough assignation. In this study, we have tried the new combinations of specific chemo with DC-CIKs immunotherapy to treat those patients. PATIENTS AND METHODS: Twenty-three metastatic anthracyclines and taxanes pretreated TNBC younger (mean 41.5 years) patients were initially mobilized with cyclophosphamide (3 g/m(2)) for the preparation of CD34(+) peripheral blood mononuclear cells as the resources for generating DC/CIKs and marrow function supports. All cases were subsequently experienced 2 cycles of chemotherapy with cyclophosphamide 3 g/m(2), thiotepa 150 mg/m(2), and carboplatin AUC = 6, Q4w. The patients then received 3 infusions of DC-CIKs at the chemo intervals and followed by maintenance therapy with oral cyclophosphamide 50 mg daily. The endpoints were progression-free survival and overall survival. RESULTS: The partial response rate was 13.0 %, stable and progressive disease rates were 56.5 and 30.4 %, respectively. The median PFS was 13.5 months (95 % confidence interval (CI) 10.1-16.9 months) and OS was 15.2 months (95 % CI 12.5-18.1 months). The most common serious adverse events were neutropenia (100.0 %) and anemia (69.7 %) but without treatment-related mortality. CONCLUSION: These data suggested that such combination therapy model be effective and safe for younger metastatic TNBC exposure to previous anthracyclines and taxanes based adjuvant chemotherapy. PMID- 26266767 TI - Implantation of autologous muscle-derived stem cells in treatment of fecal incontinence: results of an experimental pilot study. AB - BACKGROUND: The aim of this study is to present results of the implantation of autologous myoblasts into the external anal sphincter (EAS) in ten patients with fecal incontinence. METHODS: After anatomical and functional assessment of the patients' EAS, a vastus lateralis muscle open biopsy was performed. Stem cells were extracted from the biopsy specimens and cultured in vitro. Cell suspensions were then administered to the EAS. Patients were scheduled for follow-up visits in 6-week intervals. Total follow-up was 12 months. RESULTS: All biopsy and cell implantation procedures were performed without complications. Nine of the patients completed a full 12-month follow-up. There was subjective improvement in six patients (66.7 %). In manometric examinations 18 weeks after implantation, squeeze anal pressures and high-pressure zone length increased in all patients, with particularly significant sphincter function recovery in five patients (55.6 %). Electromyographic (EMG) examination showed an increase in signal amplitude in all patients, detecting elevated numbers of propagating action potentials. Twelve months after implantation two patients experienced deterioration of continence, which was also reflected in the deterioration of manometric and EMG parameters. The remaining four patients (44.4 %) still described their continence as better than before implantation and retained satisfactory functional examination parameters. CONCLUSIONS: Implantation of autologous myoblasts gives good short term results not only in a subjective assessment, but also in objective functional tests. It seems that this promising technology can improve the quality of life of patients with fecal incontinence, but further study is required to achieve better and more persistent results. PMID- 26266768 TI - Stable admission rate for acute asthma in Danish children since 1977. AB - Childhood asthma is consistently reported to have increased in recent decades in most westernized countries, but it is unknown if this increase is similar across severities. We aimed to study the time-trend of acute hospital admission and readmission for asthma of school-aged children in the recent 35 years in Denmark. We analyzed time-trends in the national incidence rate of hospitalization for acute severe asthma in children aged 5-15 in Denmark during the 35-year period 1977-2012 in the Danish national registry. Only in-patient admissions with a principal diagnosis of asthma (ICD-8: 493** or ICD-10: J45** or J46**) were included. Among children with asthma hospitalizations, we investigated the risk of readmission beyond 1 month of first admission. Admissions were summarized as rates per thousand person years at risk. The overall time-trend is stable with a rate of one admission per year per thousand children at risk and a per-year incidence rate ratio 0.999 [95 % CI 0.997-1.001]. The rate of any readmission decreased from approximately 20 per thousand children in the eighties to less than 10 in the early nineties before stabilizing at around 10 per thousand children from mid-nineties and onwards. During 35 years of nation-wide follow-up, we find a highly stable incidence rate of first hospital admission for acute severe asthma in children. Moreover, rates of readmission halved during the seventies and stabilized in the last twenty years. In conclusion, our data suggest that the reported increase in childhood asthma is mainly due to less severe cases. PMID- 26266769 TI - Answer to the letter to the editor of S. Zhang et al. concerning "Continuous wound infusion of ropivacaine for the control of pain after thoracolumbar spinal surgery: a randomized clinical trial" (by Xu B, et al. (2015) Eur Spine J; 24: doi:10.1007/s00586-015-3979-x). PMID- 26266770 TI - A case of fourth atlanto-axial facet joint: anatomical description. AB - PURPOSE: To report a rare fourth atlanto-axial joint. METHODS: A cadaveric specimen of a young male adult from occiput to C4 was dissected for anatomical study of craniocervical region. A true fourth atlanto-axial joint was confirmed. Its morphological characteristics were described. RESULTS: The fourth atlantoaxial joint is rarely seen. The possible embryogenesis is discussed. This case raises an anatomical possibility of a new variant in this region. CONCLUSIONS: A unique case with an anatomically proven fourth atlantoaxial joint is reported. This anomaly can lead to misdiagnosis. CT scan coupled with MRI can facilitate accurate diagnosis. PMID- 26266772 TI - Answer to the Letter to the Editor of L. P. Ardigo et al. concerning "The validity and reliability of "Spinal Mouse" assessment of spinal curvatures in the frontal plane in pediatric adolescent idiopathic thoracolumbar curves" by Livanelioglu A, Kaya F, Nabiyev V, Demirkiran G, Firat T (2015) Eur Spine J Apr 22 [Epub ahead of print]. PMID- 26266771 TI - Symptomatic adjacent segment degeneration at the L3-4 level after fusion surgery at the L4-5 level: evaluation of the risk factors and 10-year incidence. AB - PURPOSE: There have been few studies on revision surgery for clinically symptomatic adjacent segment degeneration (CASD). We aimed to find the incidence of revision surgery due to CASD and to analyze the factors that affected CASD at the L3-4 level after L4-5 or L4-5-S1 level fusion surgery over a long-term follow up period. METHODS: Between January 2001 and October 2009, fusion surgeries were performed on 401 patients with spondylolisthesis at the L4-5 or L4-5-S1 level; 378 patients were followed up for a minimum of 2 years. We assessed CASD-free survival using Kaplan-Meier survival analysis. We also analyzed factors affecting the development of CASD, including sex, age, pelvic incidence, overall lordosis, segmental lordosis, lamina inclination angle, facet tropism, and the extent of disc and facet degeneration. Isthmic spondylolisthesis treated using total laminectomy or degenerative spondylolisthesis treated using subtotal laminectomy and interbody fusion (IBF) or posterolateral fusion (PLF) were also included in the risk factor analysis. The difference in disc height before and after initial surgery was also analyzed, as was inclusion of the sacrum in the fusion level. RESULTS: Fusion extension surgery was performed on 33 of these patients due to CASD at the L3-4 level during the follow-up period. Kaplan-Meier survival analysis indicated 3-, 5-, and 10-year disease-free survival rates of 99.20, 96.71, and 76.93 %. Statistically significant factors affecting CASD included old age, low overall lordosis, low segmental lordosis, progression of facet degeneration, total laminectomy-treated isthmic spondylolisthesis, and PLF-alone rather than IBF alone or IBF + PLF. CONCLUSION: We determined six significant factors affecting CASD development. Among these risk factors, facet degeneration, isthmic-type spondylolisthesis, and the type of fusion show higher hazard ratios and seem to be clinically more relevant than the other three factors (age, overall lordosis, and segmental lordosis). PMID- 26266773 TI - Prevalence of tuberculosis in post-mortem studies of HIV-infected adults and children in resource-limited settings: a systematic review and meta-analysis. AB - OBJECTIVES: Tuberculosis (TB) is estimated to be the leading cause of HIV-related deaths globally. However, since HIV-associated TB frequently remains unascertained, we systematically reviewed autopsy studies to determine the true burden of TB at death. METHODS: We systematically searched Medline and Embase databases (to end 2013) for literature reporting on health facility-based autopsy studies of HIV-infected adults and/or children in resource-limited settings. Using forest plots and random-effects meta-analysis, we summarized the TB prevalence found at autopsy and used meta-regression to explore variables associated with autopsy TB prevalence. RESULTS: We included 36 eligible studies, reporting on 3237 autopsies. Autopsy TB prevalence was extremely heterogeneous (range 0-64.4%), but was markedly higher in adults [pooled prevalence 39.7%, 95% confidence interval (CI) 32.4-47.0%] compared to children (pooled prevalence 4.5%, 95% CI 1.7-7.4%). Post-mortem TB prevalence varied by world region, with pooled estimates in adults of 63.2% (95% CI 57.7-68.7%) in South Asia (n = 2 studies); 43.2% (95% CI 38.0-48.3) in sub-Saharan Africa (n = 9 studies); and 27.1% (95% CI 16.0-38.1%) in the Americas (n = 5 studies). Autopsy prevalence positively correlated with contemporary estimates of national TB prevalence. TB in adults was disseminated in 87.9% (82.2-93.7%) of cases and was considered the cause of death in 91.4% (95% CI 85.8-97.0%) of TB cases. Overall, TB was the cause of death in 37.2% (95% CI 25.7-48.7%) of adult HIV/AIDS-related deaths. TB remained undiagnosed at death in 45.8% (95% CI 32.6-59.1%) of TB cases. CONCLUSIONS: In resource-limited settings, TB accounts for approximately 40% of facility-based HIV/AIDS-related adult deaths. Almost half of this disease remains undiagnosed at the time of death. These findings highlight the critical need to improve the prevention, diagnosis and treatment of HIV-associated TB globally. PMID- 26266774 TI - Muscle fatigue resistance in the rat hindlimb in vivo from low dietary intakes of tuna fish oil that selectively increase phospholipid n-3 docosahexaenoic acid according to muscle fibre type. AB - Dietary fish oil (FO) modulates muscle O2 consumption and contractile function, predictive of effects on muscle fatigue. High doses unattainable through human diet and muscle stimulation parameters used engender uncertainty in their physiological relevance. We tested the hypothesis that nutritionally relevant FO doses can modulate membrane fatty acid composition and muscle fatigue. Male Sprague-Dawley rats were randomised to control (10% olive oil (OO) by weight) or low or moderate FO diet (LowFO and ModFO) (HiDHA tuna fish oil) for 15 weeks (LowFO: 0.3% FO, 9.7% OO, 0.25% energy as EPA+DHA; ModFO: 1.25% FO, 8.75% OO, 1.0% energy as EPA+DHA). Hindlimb muscle function was assessed under anaesthesia in vivo using repetitive 5 s burst sciatic nerve stimulation (0.05 ms, 7-12 V, 5 Hz, 10 s duty cycle, 300 s). There were no dietary differences in maximum developed muscle force. Repetitive peak developed force fell to 50% within 62 (SEM 10) s in controls and took longer to decline in FO-fed rats (LowFO 110 (SEM 15) s; ModFO 117 (sem 14) s) (P<0.05). Force within bursts was better sustained with FO and maximum rates of force development and relaxation declined more slowly. The FO-fed rats incorporated higher muscle phospholipid DHA-relative percentages than controls (P<0.001). Incorporation of DHA was greater in the fast twitch gastrocnemius (Control 9.3 (SEM 0.8) %, LowFO 19.9 (SEM 0.4), ModFO 24.3 (SEM 1.0)) than in the slow-twitch soleus muscle (Control 5.1 (SEM 0.2), LowFO 14.3 (SEM 0.7), ModFO 18.0 (SEM 1.4)) (P<0.001), which was comparable with the myocardium, in line with muscle fibre characteristics. The LowFO and ModFO diets, emulating human dietary and therapeutic supplement intake, respectively, both elicited muscle membrane DHA enrichment and fatigue resistance, providing a foundation for translating these physiological effects to humans. PMID- 26266775 TI - Monitoring heart rate variability to assess experimentally induced pain using the analgesia nociception index: A randomised volunteer study. AB - BACKGROUND: Pain assessment using a numerical rating scale (NRS) is considered good clinical practice, but objective assessment in noncommunicating patients is still a challenge. A potential solution is to monitor changes in heart rate variability transformed into the analgesia nociception index (ANI), that offers a noninvasive means of pain quantification. OBJECTIVES: The aim was to measure magnitudes, descending slopes and time courses of ANI following expected and unexpected painful, nonpainful and sham experimental stimuli and compare these with pain intensity as assessed by NRS in conscious human volunteers. We expected a negative correlation between ANI and NRS after painful stimuli. DESIGN: Randomised stimuli and placebo-controlled, single-blinded study. SETTING: Experimental pain simulation laboratory, Bochum, Germany. PARTICIPANTS: Twenty healthy male students, (mean +/- standard deviation; 24.2 +/- 1.9 years) recruited via local advertising, were consecutively included. INTERVENTION: ANI values were continuously recorded. After resting, four stimuli were applied in a random order on the right forearm (unexpected and expected electrical pain, expected nonpainful and sham stimuli). Blinded volunteers were asked to rate all four stimuli on NRS. MAIN OUTCOME MEASURES: ANI means (0-100), amplitudes, maxima, minima and slopes with NRS pain intensity scores (0-10). RESULTS: Resting alert volunteers showed ANI values of 82.05 +/- 10.71. ANI decreased after a random stimulus (maximal decrease of 25.0 +/- 7.3%), but different kinds of stimuli evoked similar results. NRS scores (median; interquartiles) were significantly (P = 0.008) higher after expected (5.25; 3.5-6.75) compared with unexpected (4.50; 3.0-5.0) pain stimuli. No correlation was found between ANI and NRS. CONCLUSION: ANI did not allow a differentiation of painful, nonpainful or sham stimuli in alert volunteers. Therefore, ANI does not exclusively detect nociception, but may be modified by stress and emotion. Thus, we conclude that ANI is not a specific, robust measure for assessment of pain intensity. PMID- 26266776 TI - Podocyte and endothelial injury in focal segmental glomerulosclerosis: an ultrastructural analysis. AB - Podocyte injury contributes to the development of focal segmental glomerulosclerosis (FSGS). Endocapillary hypercellularity, which is one of the pathological characteristics of FSGS, suggests that glomerular endothelial injury may also be involved in the pathogenesis of FSGS. In electron micrographs of patients with FSGS (n = 43), we conducted morphometric measurements of foot process width (FPW) and podocyte detachment (PD) as markers of podocyte injury and subendothelial widening (SW) of the glomerular basement membrane as a marker of endothelial injury and compared them to those in patients with minimal change nephrotic syndrome (MCNS; n = 11) and control kidney donors (n = 5). Associations between ultrastructural and clinical parameters were analyzed according to the FSGS variants defined by the Columbia classification. FPW was significantly higher in the FSGS group than that in the MCNS and control groups, particularly in the collapsing, tip, and cellular variants of FSGS. Percentage of glomerular basement membrane (GBM) length showing PD and SW was significantly increased in the FSGS group, especially in the collapsing, cellular, and not otherwise specified variants. In FSGS, FPW was inversely correlated with disease duration, but not with proteinuria. Finally, the percentage of GBM length with SW significantly correlated with clinical parameters indicative of poor prognosis, such as lower remission rate and lower estimated glomerular filtration rate at the final observation. Quantitative measurement of podocyte and endothelial injury by electron microscopy might be useful for evaluating histological activity and predicting prognosis in FSGS. PMID- 26266777 TI - Primary thymic cholesteroloma: a clinicopathological correlation of four cases of an unusual benign lesion. AB - Four cases of an unusual thymic lesion characterized by the presence of extensive cholesterol cleft granulomata are presented. The patients were four men between the ages of 58 and 71 years (average 64.5 years). The anterior mediastinal masses were discovered during radiological evaluation, in one patient for cardiac disease and one for Barrett's esophagus. Another patient was symptomatic with cough and dyspnea while the fourth was asymptomatic and the lesion was discovered during routine chest imaging. Complete surgical resection was performed in all four patients. The resected lesions were described as tumor-like masses measuring between 2 and 6 cm in greatest diameter. Histologically, all cases showed identical features, mainly the presence of cholesterol cleft granulomata in an alveolar-like growth pattern. Foreign body-type giant cells and an inflammatory reaction were identified in all cases as well as the presence of remnants of thymic tissue. Clinical follow-up in these patients showed that all are alive and well without evidence of recurrence. The current cases highlight an unusual tumoral thymic lesion that can be clinically confused for an aggressive tumor and that will require complete surgical resection for definitive diagnosis. PMID- 26266778 TI - [Progress in genetic research of human height]. AB - It is well known that both environmental and genetic factors contribute to adult height variation in general population. However, heritability studies have shown that the variation in height is more affected by genetic factors. Height is a typical polygenic trait which has been studied by traditional linkage analysis and association analysis to identify common DNA sequence variation associated with height, but progress has been slow. More recently, with the development of genotyping and DNA sequencing technologies, tremendous achievements have been made in genetic research of human height. Hundreds of single nucleotide polymorphisms (SNPs) associated with human height have been identified and validated with the application of genome-wide association studies (GWAS) methodology, which deepens our understanding of the genetics of human growth and development and also provides theoretic basis and reference for studying other complex human traits. In this review, we summarize recent progress in genetic research of human height and discuss problems and prospects in this research area which may provide some insights into future genetic studies of human height. PMID- 26266779 TI - [The biological functions and regulations of competing endogenous RNA]. AB - Recent studies demonstrate that RNA species could regulate each other by competing for shared microRNA response elements (MREs). This regulatory model is called competing endogenous RNA (ceRNA). Currently, the identified ceRNAs cover coding and non-coding RNAs. The latter includes pseudogene transcripts, long non coding RNAs (lncRNAs), circular RNAs (circRNAs) and so on. In this review, we summarize the biological functions of regulatory networks consisting of various types of ceRNAs and their roles in the pathological and physiological processes. Additionally, several factors that may regulate ceRNAs were discussed. PMID- 26266780 TI - [Recent progress in gene mapping through high-throughput sequencing technology and forward genetic approaches]. AB - Traditional gene mapping using forward genetic approaches is conducted primarily through construction of a genetic linkage map, the process of which is tedious and time-consuming, and often results in low accuracy of mapping and large mapping intervals. With the rapid development of high-throughput sequencing technology and decreasing cost of sequencing, a variety of simple and quick methods of gene mapping through sequencing have been developed, including direct sequencing of the mutant genome, sequencing of selective mutant DNA pooling, genetic map construction through sequencing of individuals in population, as well as sequencing of transcriptome and partial genome. These methods can be used to identify mutations at the nucleotide level and has been applied in complex genetic background. Recent reports have shown that sequencing mapping could be even done without the reference of genome sequence, hybridization, and genetic linkage information, which made it possible to perform forward genetic study in many non-model species. In this review, we summarized these new technologies and their application in gene mapping. PMID- 26266781 TI - [Plastid genome engineering: novel optimization strategies and applications]. AB - The plastid genome engineering system allows site-specific modifications via two homologous recombination events. It is much safer, more precise and efficient compared with the nuclear transformation system. This technology can be applied to the basic research to expand plastid genome function analysis, and it also provides an excellent platform for not only high-level production of recombinant proteins but also plant breeding. In this review, we summarize the state of the art and progresses in this field. We focus on novel breeding strategies in transformation system improvement and new tools to enhance plastid transgene expression levels. In addition, we highlight selected applications in resistance engineering and quality improvement via metabolic engineering. We believe that by overcoming current technological limitations in the plastid transformation system can another green revolution for crop breeding beckon. PMID- 26266782 TI - [The roles of epigenetics and protein post-translational modifications in bacterial antibiotic resistance]. AB - The increasing antibiotic resistance is now threatening to take us back to a pre antibiotic era. Bacteria have evolved diverse resistance mechanisms, on which in depth research could help the development of new strategies to control antibiotic resistant infections. Epigenetic alterations and protein post-translational modifications (PTMs) play important roles in multiple cellular processes such as metabolism, signal transduction, protein degradation, DNA replication regulation and stress response. Recent studies demonstrated that epigenetics and PTMs also play vital roles in bacterial antibiotic resistance. In this review, we summarize the regulatory roles of epigenetic factors including DNA methylation and regulatory RNAs as well as PTMs such as phosphorylation and succinylation in bacterial antibiotic resistance, which may provide innovative perspectives on selecting antibacterial targets and developing antibiotics. PMID- 26266783 TI - [Functional analysis of autism-associated NRXN1beta gene promoter]. AB - Neurexins are neuron-specific synaptic proteins, and abnormal structure of Neurexin1beta is closely associated with autism. To characterize the minimal promoter of autism-associated NRXN1beta gene and identify functional elements regulating its transcription, luciferase reporter plasmids containing different regulatory regions upstream of NRXN1beta gene were constructed. After transfecting HEK293 cells with these plasmids, the minimal promoter region of NRXN1beta gene was determined by detecting the transcriptional activity of luciferase reporter genes while the corresponding functional elements that significantly enhance or inhibit the activity of reporter genes were further screened out. To identify cis-acting elements, continuous nucleotide mutation within the functional regions and adjacent DNA sequences were generated using site-directed mutagenesis techniques and then transcriptional regulatory elements in corresponding regions were analyzed using transcription factor binding prediction tool. Our results showed for the first time that the minimal promoter region of human NRXN1beta gene is located between positions -88 and +156 ( 88/+156); two regions -88/-73 and +156/+149 enhance while the region +229/+419 inhibits promoter activity. The region -84/-63 significantly enhances promoter activity as cis-acting elements, suggesting the presence of DBP and ABF1 transcription factor binding sites in this region. PMID- 26266784 TI - [A genome-wide association study on body weight traits of Jinghai yellow chicken]. AB - Body weight traits are important economic characters of broilers. This study was carried out to screen for molecular markers and candidate genes that can be used to improve the body weight traits. A herd of 400 female Jinghai yellow chickens were measured for body weights from 0 to 14 weeks of age. Genome-wide association study (GWAS) was carried out using specific-locus amplified fragment sequencing (SLAF-seq) technology to detect SNPs associated with body weight traits of Jinghai yellow chicken. Finally, 100 SNPs that associated with body weight traits were detected. The results showed that effects of 15 SNPs reached 5% Bonferroni genome-wide significance and 85 SNPs reached potential genome-wide significance. Genes in the candidate regions with 1 Mb windows (SNP position+/-0.5 Mb) surrounding each significant SNP were screened. Finally, nine candidate genes were obtained, among which four genes of FAM124A (Family with sequence similarity 124A), QDPR (Quinoid dihydropteridine reductase), WDR1 (WD repeat domain 1) and SLC2A9 (Solute carrier family 2 (facilitated glucose transporter), member 9) might be important candidate genes influencing body weight traits of Jinghai yellow chicken. Furthermore, it was also found that most SNPs associated with mid and late growth and body weights were intensively located in the region of 75.6 80.7 Mb on chromosome 4. Our study thus provides a basis for genetic understanding of the Jinghai yellow chicken body weight traits. PMID- 26266785 TI - [Effects of transgenic cotton expressing chitinase and glucanase genes on the diversity of soil bacterial community]. AB - The transgenic cotton expressing chitinase and glucanase genes was studied using nontransgenic cotton as a control. Specifically, the effects of exogenous genes on bacterial community diversity in rhizospheres of cotton at stages of seedling, budding, boll forming and boll opening were evaluated through comparing the number of cultivable bacteria and analyzing 16S rRNA gene clone libraries. The results showed that the number of cultivable bacteria was not affected by exogenous genes but the cotton growth period, and the number peaked at the stage of boll forming with vigorous metabolism. The 16S rRNA gene clone library prepared from soil bacteria in rhizospheres of transgenic and nontransgenic cotton at different stages contained 2400 clones which covered 283 genera. Among them, Acidobacterium was the most dominant group which contained 642 clones, followed by unclassified bacterium and Flavisolibacter. Compared with nontransgenic cotton, the rhizosphere bacterial diversity of transgenic cotton exhibited lower level at the same growth stage, however, their common bacterial communities increased with growth and development. Our results suggest that chitinase and glucanase genes decrease the rhizosphere bacterial diversity at distinct degrees, however, the difference of bacterial diversity between transgenic and nontransgenic cotton reduces gradually with the extension of cultivation period. PMID- 26266786 TI - [Transcriptome analysis of Dunaliella viridis]. AB - In order to understand the gene information, function, haloduric pathway (glycerolipid metabolism) and related key genes for Dunaliella viridis, we used Illumina HiSeqTM 2000 high-throughput sequencing technology to sequence its transcriptome. Trinity soft was used to assemble the data to form transcripts. Based on the Clusters of Orthologous Groups (COG), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG ) databases, we carried out functional annotation and classification, pathway annotation, and the opening reading fragment (ORF) sequence prediction of transcripts. The key genes in the glycerolipid metabolism were analyzed. The results suggested that 81,593 transcripts were found, and 77,117 ORF sequences were predicted, accounting for 94.50% of all transcripts. COG classification results showed that 16,569 transcripts were assigned to 24 categories. GO classification annotated 76,436 transcripts. The number of transcripts for biologcial processes was 30,678, accounting for 40.14% of all transcripts. KEGG pathway analysis showed that 26,428 transcripts were annotated to 317 pathways, and 131 pathways were related to metabolism, accounting for 41.32% of all annotated pathways. Only one transcript was annotated as coding the key enzyme dihydroxyacetone kinase involved in the glycerolipid pathway. This enzyme could be related to glycerol biosynthesis under salt stress. This study further improved the gene information and laid the foundation of metabolic pathway research for Dunaliella viridis. PMID- 26266787 TI - [The study of tomato fruit weight quantitative trait locus and its application in genetics teaching]. AB - The classical research cases, which have greatly promoted the development of genetics in history, can be combined with the content of courses in genetics teaching to train students' ability of scientific thinking and genetic analysis. The localization and clone of gene controlling tomato fruit weight is a pioneer work in quantitative trait locus (QTL) studies and represents a complete process of QTL research in plants. Application of this integrated case in genetics teaching, which showed a wonderful process of scientific discovery and the fascination of genetic research, has inspired students' interest in genetics and achieved a good teaching effect. PMID- 26266788 TI - In response to A new theory on the pathogenesis of acquired cholesteatoma: Mucosal traction. PMID- 26266789 TI - A new dawn for critical care research. PMID- 26266790 TI - Adrenomedullin binding improves catecholamine responsiveness and kidney function in resuscitated murine septic shock. AB - PURPOSE: Adrenomedullin (ADM) has been referred to as a double-edged sword during septic shock: On one hand, ADM supplementation improved organ perfusion and function, attenuated systemic inflammation, and ultimately reduced tissue apoptosis and mortality. On the other hand, ADM overproduction can cause circulatory collapse and organ failure due to impaired vasoconstrictor response and reduced myocardial contractility. Since most of these data originate from un resuscitated shock models, we tested the hypothesis whether the newly developed anti-ADM antibody HAM1101 may improve catecholamine responsiveness and thus attenuate organ dysfunction during resuscitated murine, cecal ligation and puncture (CLP)-induced septic shock. METHODS: Immediately after CLP, mice randomly received vehicle (phosphate-buffered saline, n = 11) or HAM1101 (n = 9; 2 MUg.g(-1)). Fifteen hours after CLP, animals were anesthetized, mechanically ventilated, instrumented, and resuscitated with hydroxyethylstarch and continuous i.v. norepinephrine to achieve normotensive hemodynamics (mean arterial pressure > 50 to 60 mmHg). RESULTS: HAM1101 pretreatment reduced the norepinephrine infusion rates required to achieve hemodynamic targets, increased urine flow, improved creatinine clearance, and lowered neutrophil gelatinase-associated lipocalin blood levels, which coincided with reduced expression of the inducible nitric oxide synthase and formation of peroxynitrite (nitrotyrosine immunostaining) in the kidney and aorta, ultimately resulting in attenuated systemic inflammation and tissue apoptosis. CONCLUSIONS: During resuscitated murine septic shock, early ADM binding with HAM1101 improved catecholamine responsiveness, blunted the shock-related impairment of energy metabolism, reduced nitrosative stress, and attenuated systemic inflammatory response, which was ultimately associated with reduced kidney dysfunction and organ injury. PMID- 26266791 TI - Epitope specificity of anti-Adrenomedullin antibodies determines efficacy of mortality reduction in a cecal ligation and puncture mouse model. AB - INTRODUCTION: Adrenomedullin (ADM), a circulating vasodilatory peptide, plays an important role in the development of sepsis-associated hemodynamic and microcirculatory disorders. While administration of exogenous ADM had beneficial effects in several septic animal models, elevated ADM concentrations are associated with a bad outcome. This prompted us to test the effect of various anti-ADM antibodies in a cecal ligation and puncture (CLP) mouse model. METHODS: To gain new potential compounds for the treatment or prevention of septic shock we followed an alternative strategy to influence the ADM system: High-affinity anti-ADM antibodies with different epitope specificities were developed and their antagonist activity in vitro and their ability to reduce mortality in a CLP mouse model were assessed. RESULTS: An anti-ADM antibody directed against the N terminus substantially increased the survival of mice in a CLP model (HR = 0.077 (CI = 0.0189 to 0.315), p = 0.0004), whereas other antibodies with similar affinities but different epitope specificities were much less potent. The efficacious antibody, in contrast to an anti-C-terminal antibody, only partially inhibited ADM agonist activity in vitro. Healthy mice were not negatively affected by the N-terminal antibody. CONCLUSIONS: An anti-N-terminal ADM antibody, as opposed to antibodies with other epitope specificities, strongly reduces mortality in CLP mice. PMID- 26266792 TI - Acid-base changes after fluid bolus: sodium chloride vs. sodium octanoate. AB - OBJECTIVES: This study aims to test the hypothesis that fluid loading with sodium chloride (150 mmol Na and 150 mmol Cl) or sodium octanoate (150 mmol Na, 100 mmol Cl, and 50 mmol octanoate) would lead to different acid-base changes. DESIGN: We performed a double-blind crossover experimental study. SETTING: The study was done at a University Physiology Laboratory. SUBJECTS: Eight Merino ewes were used as subjects. MEASUREMENTS AND MAIN RESULTS: We randomly assigned animals to a rapid intravenous infusion (1 L over 30 min) of either normal saline (NS) or sodium octanoate solution (OS). We collected blood samples at 0.5, 1, 2, 4, and 6 h after the start of the infusion for blood gas analyses and biochemistry. We calculated strong ion difference apparent (SIDa), effective strong ion difference, and strong ion gap (SIG). Animals in the NS group developed metabolic acidification immediately after fluid administration (pH 7.49 to 7.42, base excess 3.0 to -1.6 mEq/L), while the OS group did not (pH 7.47 to 7.51, base excess 1.1 to 1.4 mEq/L; P < 0.001). Additionally, the OS group had higher SIDa (36.2 vs. 33.2 mEq/L) and SIG (7.4 vs. 6.2 mEq/L) at the end of the infusion. CONCLUSIONS: Our findings provide further evidence that acidification induced by intravenous fluid loading is dependent on fluid composition and challenges the paradigm of the so-called dilutional acidosis. PMID- 26266793 TI - Activated protein C ameliorates impaired renal microvascular oxygenation and sodium reabsorption in endotoxemic rats. AB - INTRODUCTION: We aimed to test whether continuous recombinant human activated protein C (APC) administration would be able to protect renal oxygenation and function during endotoxemia in order to provide more insight into the role of coagulation and inflammation in the development of septic acute kidney injury. METHODS: In anesthetized, mechanically ventilated Wistar rats, endotoxemia was induced by lipopolysaccharide administration (10 mg/kg i.v. over 30 min). One hour later, the rats received fluid resuscitation with 0 (LPS + FR group; n = 8), 10 (APC10 group; n = 8), or 100 (APC100 group; n = 8) MUg/kg/h APC for 2 h. Renal microvascular oxygenation in the cortex and medulla were measured using phosphorimetry, and renal creatinine clearance rate and sodium reabsorption were measured as indicators of renal function. Statistical significance of differences between groups was tested using two-way ANOVA with Bonferroni post hoc tests. RESULTS: APC did not have notable effects on systemic and renal hemodynamic and oxygenation variables or creatinine clearance. The changes in renal microvascular oxygenation in both the cortex (r = 0.66; p < 0.001) and medulla (r = 0.80; p < 0.001) were correlated to renal sodium reabsorption. CONCLUSION: Renal sodium reabsorption is closely correlated to renal microvascular oxygenation during endotoxemia. In this study, fluid resuscitation and APC supplementation were not significantly effective in protecting renal microvascular oxygenation and renal function. The specific mechanisms responsible for these effects of APC warrant further study. PMID- 26266795 TI - A mouse is not a rat is not a man: species-specific metabolic responses to sepsis - a nail in the coffin of murine models for critical care research? PMID- 26266794 TI - The metabolic phenotype of rodent sepsis: cause for concern? AB - PURPOSE: Rodent models of sepsis are frequently used to investigate pathophysiological mechanisms and to evaluate putative therapeutic strategies. However, preclinical efficacy in these models has failed to translate to the clinical setting. We thus questioned the representativeness of such models and herein report a detailed comparison of the metabolic and cardiovascular phenotypes of long-term faecal peritonitis in fluid-resuscitated rats and mice with similar mortality profiles. METHODS: We conducted prospective laboratory controlled studies in adult male Wistar rats and C57 black mice. Animals were made septic by intraperitoneal injection of faecal slurry. Rats received continuous intravenous fluid resuscitation, whereas mice received intermittent fluid boluses subcutaneously. Sham-treated animals served as controls. Survival was assessed over 72 h. In separate studies, whole body metabolism (O2 consumption, CO2 production) was measured over 24 h with echocardiography performed at early (6 h) and established (24 h) phases of sepsis. Blood gas analysis was performed at 6 h (rats) and 24 h (rats, mice). RESULTS: Similar survival curves were seen in both rodent models with approximately 75% mortality at 72 h. In mice, sepsis caused severity-dependent falls in core temperature and global metabolism. Oxygen consumption in severely septic mice fell by 38% within 2 h, and 80% at 22 h compared with baseline values. This was only partially restored by external warming. By contrast, septic rats maintained core temperature; only severely affected animals showed a pre-mortem decline in oxygen consumption. Significant myocardial dysfunction was seen in mice during early and established sepsis, whereas peak velocity and other hemodynamic variables in rats were similar at 6 h and significantly worse by 24 h in severely septic animals only. CONCLUSIONS: Markedly differing metabolic and cardiovascular profiles were seen in long-term fluid-resuscitated rat and mouse models of bacterial sepsis despite similar mortality. The mouse model, in particular, does not represent the human condition. We urge caution in applying findings in murine models to septic patients, both with regard to our understanding of pathophysiology and the failure to translate preclinical efficacy into successful clinical trials. PMID- 26266796 TI - IL-1beta processing in mechanical ventilation-induced inflammation is dependent on neutrophil factors rather than caspase-1. AB - PURPOSE: Mechanical ventilation can cause ventilator-induced lung injury, characterized by a sterile inflammatory response in the lungs resulting in tissue damage and respiratory failure. The cytokine interleukin-1beta (IL-1beta) is thought to play an important role in the pathogenesis of ventilator-induced lung injury. Cleavage of the inactive precursor pro-IL-1beta to form bioactive IL 1beta is mediated by several types of proteases, of which caspase-1, activated within the inflammasome, is the most important. Herein, we studied the roles of IL-1beta, caspase-1 and neutrophil factors in the mechanical ventilation-induced inflammatory response in mice. METHODS: Untreated wild-type mice, IL-1alphabeta knockout and caspase-1 knockout mice, pralnacasan (a selective caspase-1 inhibitor)-treated mice, anti-keratinocyte-derived chemokine (KC)-treated mice and cyclophosphamide-treated neutrophil-depleted wild-type mice were ventilated using clinically relevant ventilator settings (tidal volume 8 ml/kg). The lungs and plasma were collected to determine blood gas values, cytokine profiles and neutrophil influx. RESULTS: Mechanical ventilation resulted in increased pulmonary concentrations of IL-1beta and KC and increased pulmonary neutrophil influx compared with non-ventilated mice. Ventilated IL-1alphabeta knockout mice did not demonstrate this increase in cytokines. No significant differences were observed between wild-type and caspase-1-deficient or pralnacasan-treated mice. In contrast, in anti-KC antibody-treated mice and neutropenic mice, inflammatory parameters decreased in comparison with ventilated non-treated mice. CONCLUSIONS: Our results illustrate that IL-1 is indeed an important cytokine in the inflammatory cascade induced by mechanical ventilation. However, the inflammasome/caspase-1 appears not to be involved in IL-1beta processing in this type of inflammatory response. The attenuated inflammatory response observed in ventilated anti-KC-treated and neutropenic mice suggests that IL-1beta processing in mechanical ventilation-induced inflammation is mainly mediated by neutrophil factors. PMID- 26266797 TI - Effects of the PPAR-beta/delta agonist GW0742 during resuscitated porcine septic shock. AB - BACKGROUND: In un-resuscitated rodent models of septic shock, the peroxisome proliferator-activated receptor-beta/delta (PPAR-beta/delta) agonist GW0742 improved visceral organ function. Therefore, we tested the hypothesis whether GW0742 would attenuate kidney injury during long-term, resuscitated, porcine polymicrobial septic shock. METHODS: Six, 12, and 18 h after the induction of fecal peritonitis by inoculation of autologous feces, anesthetized, mechanically ventilated, and instrumented male pigs with pre-existing atherosclerosis resulting from familial hypercholesteremia and atherogenic diet randomly received either vehicle (dimethyl sulfoxide, n = 12) or GW0742 (n = 10). Resuscitation comprised hydroxyethyl starch and norepinephrine infusion titrated to maintain mean arterial pressure at baseline values. RESULTS: Despite aggressive fluid resuscitation, fecal peritonitis was associated with arterial hypotension requiring norepinephrine infusion, ultimately resulting in progressive lactic acidosis and acute kidney injury. GW0742 did not beneficially affect any parameter of systemic and regional hemodynamics, gas exchange, metabolism, or organ function. The parameters of inflammation, oxidative and nitrosative stress, and organ injury (post-mortem analysis for histomorphology and markers of apoptosis) were not influenced either. Immunohistochemistry of pre-shock kidney biopsies from a previous study in this swine strain showed markedly lower PPAR beta/delta receptor expression than in healthy animals. CONCLUSIONS: In swine with pre-existing atherosclerosis, the PPAR-beta/delta agonist GW0742 failed to attenuate septic shock-induced circulatory failure and kidney dysfunction, most likely due to reduced receptor expression coinciding with cardiovascular and metabolic co-morbidity. PMID- 26266798 TI - Malignant perivascular epithelioid cell tumour with rhabdomyosarcomatous differentiation of the pelvic cavity. PMID- 26266799 TI - HbA1c alone is a poor indicator of cardiometabolic risk in middle-aged subjects with pre-diabetes but is suitable for type 2 diabetes diagnosis: a cross sectional study. AB - OBJECTIVES: Glycated haemoglobin A1c (HbA1c) measurement is recommended as an alternative to fasting plasma glucose (FPG) for the diagnosis of pre-diabetes and type 2 diabetes. However, evidence suggests discordance between HbA1c and FPG. In this study we examine a range of metabolic risk features, pro-inflammatory cytokines, acute-phase response proteins, coagulation factors and white blood cell counts to determine which assay more accurately identifies individuals at increased cardiometabolic risk. MATERIALS AND METHODS: This was a cross-sectional study involving a random sample of 2,047 men and women aged 46-73 years. Binary and multinomial logistic regression were employed to examine risk feature associations with pre-diabetes [either HbA1c levels 5.7-6.4% (39-46 mmol/mol) or impaired FPG levels 5.6-6.9 mmol/l] and type 2 diabetes [either HbA1c levels >6.5% (>48 mmol/mol) or FPG levels >7.0 mmol/l]. Receiver operating characteristic curve analysis was used to evaluate the ability of HbA1c to discriminate pre-diabetes and diabetes defined by FPG. RESULTS: Stronger associations with diabetes-related phenotypes were observed in pre-diabetic subjects diagnosed by FPG compared to those detected by HbA1c. Individuals with type 2 diabetes exhibited cardiometabolic profiles that were broadly similar according to diagnosis by either assay. Pre-diabetic participants classified by both assays displayed a more pro-inflammatory, pro-atherogenic, hypertensive and insulin resistant profile. Odds ratios of having three or more metabolic syndrome features were also noticeably increased (OR: 4.0, 95% CI: 2.8-5.8) when compared to subjects diagnosed by either HbA1c (OR: 1.4, 95% CI: 1.2-1.8) or FPG (OR: 3.0, 95% CI: 1.7-5.1) separately. CONCLUSIONS: In middle-aged Caucasian-Europeans, HbA1c alone is a poor indicator of cardiometabolic risk but is suitable for diagnosing diabetes. Combined use of HbA1c and FPG may be of additional benefit for detecting individuals at highest odds of type 2 diabetes development. PMID- 26266800 TI - 7, 8-Dihydroxyflavone Protects an Endothelial Cell Line from H2O2 Damage. AB - 7, 8-dihydroxyflavone (7, 8-DHF), a selective agonist for TrkB receptors, has been well studied for its neurotrophic functions. However, its roles outside the neural tissues have scarcely been studied as yet. In this study, we investigated the protecting roles of 7, 8-DHF in EA.hy926 cells, a human umbilic vein endothelial cell line which was exposed to hydrogen peroxide (H2O2). We found that 7, 8-DHF significantly protected the cells from being damaged by H2O2 through suppression of apoptosis, attenuation of inflammatory factor releasing and inhibition of reactive oxygen species generation. The potent biological effects of 7, 8-DHF were probably executed via its binding to TrkB receptors because the receptor specific antagonist ANA-12 significantly blocked its protecting effects. The protecting roles of 7, 8-DHF in EA.hy926 cells suggest that it will be a promising compound to be developed into a health product that definitely benefits endothelial functions and prevents cardiovascular diseases. PMID- 26266801 TI - A comparison of the biological effects of 125I seeds continuous low-dose-rate radiation and 60Co high-dose-rate gamma radiation on non-small cell lung cancer cells. AB - OBJECTIVES: To compare the biological effects of 125I seeds continuous low-dose rate (CLDR) radiation and 60Co gamma-ray high-dose-rate (HDR) radiation on non small cell lung cancer (NSCLC) cells. MATERIALS AND METHODS: A549, H1299 and BEAS 2B cells were exposed to 125I seeds CLDR radiation or 60Co gamma-ray HDR radiation. The survival fraction was determined using a colony-forming assay. The cell cycle progression and apoptosis were detected by flow cytometry (FCM). The expression of the apoptosis-related proteins caspase-3, cleaved-caspase-3, PARP, cleaved-PARP, BAX and Bcl-2 were detected by western blot assay. RESULTS: After irradiation with 125I seeds CLDR radiation, there was a lower survival fraction, more pronounced cell cycle arrest (G1 arrest and G2/M arrest in A549 and H1299 cells, respectively) and a higher apoptotic ratio for A549 and H1299 cells than after 60Co gamma-ray HDR radiation. Moreover, western blot assays revealed that 125I seeds CLDR radiation remarkably up-regulated the expression of Bax, cleaved caspase-3 and cleaved-PARP proteins and down-regulated the expression of Bcl-2 proteins in A549 and H1299 cells compared with 60Co gamma-ray HDR radiation. However, there was little change in the apoptotic ratio and expression of apoptosis-related proteins in normal BEAS-2B cells receiving the same treatment. CONCLUSIONS: 125I seeds CLDR radiation led to remarkable growth inhibition of A549 and H1299 cells compared with 60Co HDR gamma-ray radiation; A549 cells were the most sensitive to radiation, followed by H1299 cells. In contrast, normal BEAS-2B cells were relatively radio-resistant. The imbalance of the Bcl-2/Bax ratio and the activation of caspase-3 and PARP proteins might play a key role in the anti-proliferative effects induced by 125I seeds CLDR radiation, although other possibilities have not been excluded and will be investigated in future studies. PMID- 26266802 TI - Reliability and Validity Study of Clinical Ultrasound Imaging on Lateral Curvature of Adolescent Idiopathic Scoliosis. AB - BACKGROUND: Non-ionizing radiation imaging assessment has been advocated for the patients with adolescent idiopathic scoliosis (AIS). As one of the radiation-free methods, ultrasound imaging has gained growing attention in scoliosis assessment over the past decade. The center of laminae (COL) method has been proposed to measure the spinal curvature in the coronal plane of ultrasound image. However, the reliability and validity of this ultrasound method have not been validated in the clinical setting. OBJECTIVES: To evaluate the reliability and validity of clinical ultrasound imaging on lateral curvature measurements of AIS with their corresponding magnetic resonance imaging (MRI) measurements. METHODS: Thirty curves (ranged 10.2 degrees -68.2 degrees ) from sixteen patients with AIS were eligible for this study. The ultrasound scan was performed using a 3-D ultrasound unit within the same morning of MRI examination. Two researchers were involved in data collection of these two examinations. The COL method was used to measure the coronal curvature in ultrasound image, compared with the Cobb method in MRI. The intra- and inter-rater reliability of the COL method was evaluated by intra-class correlation coefficient (ICC). The validity of this method was analyzed by paired Student's t-test, Bland-Altman statistics and Pearson correlation coefficient. The level of significance was set as 0.05. RESULTS: The COL method showed high intra- and inter-rater reliabilities (both with ICC (2, K) >0.9, p<0.05) to measure the coronal curvature. Compared with Cobb method, COL method showed no significant difference (p<0.05) when measuring coronal curvature. Furthermore, Bland-Altman method demonstrated an agreement between these two methods, and Pearson's correlation coefficient (r) was high (r>0.9, p<0.05). CONCLUSION: The ultrasound imaging could provide a reliable and valid measurement of spinal curvature in the coronal plane using the COL method. Further research is needed to validate the proposed ultrasound measurement in larger clinical trial and to optimize the ultrasound scanning and measuring procedure. PMID- 26266803 TI - Regeneration patterns of European oak species (Quercus petraea (Matt.) Liebl., Quercus robur L.) in dependence of environment and neighborhood. AB - Quercus robur L. (pedunculate oak) and Quercus petraea (Matt.) Liebl. (sessile oak) are two European oak species of great economic and ecological importance. Even though both oaks have wide ecological amplitudes of suitable growing conditions, forests dominated by oaks often fail to regenerate naturally. The regeneration performance of both oak species is assumed to be subject to a variety of variables that interact with one another in complex ways. The novel approach of this research was to study the effect of many ecological variables on the regeneration performance of both oak species together and identify key variables and interactions for different development stages of the oak regeneration on a large scale in the field. For this purpose, overstory and regeneration inventories were conducted in oak dominated forests throughout southern Germany and paired with data on browsing, soil, and light availability. The study was able to verify the assumption that the occurrence of oak regeneration depends on a set of variables and their interactions. Specifically, combinations of site and stand specific variables such as light availability, soil pH and iron content on the one hand, and basal area and species composition of the overstory on the other hand. Also browsing pressure was related to oak abundance. The results also show that the importance of variables and their combinations differs among the development stages of the regeneration. Light availability becomes more important during later development stages, whereas the number of oaks in the overstory is important during early development stages. We conclude that successful natural oak regeneration is more likely to be achieved on sites with lower fertility and requires constantly controlling overstory density. Initially sufficient mature oaks in the overstory should be ensured. In later stages, overstory density should be reduced continuously to meet the increasing light demand of oak seedlings and saplings. PMID- 26266804 TI - Extinction events can accelerate evolution. AB - Extinction events impact the trajectory of biological evolution significantly. They are often viewed as upheavals to the evolutionary process. In contrast, this paper supports the hypothesis that although they are unpredictably destructive, extinction events may in the long term accelerate evolution by increasing evolvability. In particular, if extinction events extinguish indiscriminately many ways of life, indirectly they may select for the ability to expand rapidly through vacated niches. Lineages with such an ability are more likely to persist through multiple extinctions. Lending computational support for this hypothesis, this paper shows how increased evolvability will result from simulated extinction events in two computational models of evolved behavior. The conclusion is that although they are destructive in the short term, extinction events may make evolution more prolific in the long term. PMID- 26266805 TI - Does Interdisciplinary Research Lead to Higher Citation Impact? The Different Effect of Proximal and Distal Interdisciplinarity. AB - This article analyses the effect of degree of interdisciplinarity on the citation impact of individual publications for four different scientific fields. We operationalise interdisciplinarity as disciplinary diversity in the references of a publication, and rather than treating interdisciplinarity as a monodimensional property, we investigate the separate effect of different aspects of diversity on citation impact: i.e. variety, balance and disparity. We use a Tobit regression model to examine the effect of these properties of interdisciplinarity on citation impact, controlling for a range of variables associated with the characteristics of publications. We find that variety has a positive effect on impact, whereas balance and disparity have a negative effect. Our results further qualify the separate effect of these three aspects of diversity by pointing out that all three dimensions of interdisciplinarity display a curvilinear (inverted U-shape) relationship with citation impact. These findings can be interpreted in two different ways. On the one hand, they are consistent with the view that, while combining multiple fields has a positive effect in knowledge creation, successful research is better achieved through research efforts that draw on a relatively proximal range of fields, as distal interdisciplinary research might be too risky and more likely to fail. On the other hand, these results may be interpreted as suggesting that scientific audiences are reluctant to cite heterodox papers that mix highly disparate bodies of knowledge--thus giving less credit to publications that are too groundbreaking or challenging. PMID- 26266806 TI - Uncovering the differential molecular basis of adaptive diversity in three Echinochloa leaf transcriptomes. AB - Echinochloa is a major weed that grows almost everywhere in farmed land. This high prevalence results from its high adaptability to various water conditions, including upland and paddy fields, and its ability to grow in a wide range of climates, ranging from tropical to temperate regions. Three Echinochloa crus galli accessions (EC-SNU1, EC-SNU2, and EC-SNU3) collected in Korea have shown diversity in their responses to flooding, with EC-SNU1 exhibiting the greatest growth among three accessions. In the search for molecular components underlying adaptive diversity among the three Echinochloa crus-galli accessions, we performed de novo assembly of leaf transcriptomes and investigated the pattern of differentially expressed genes (DEGs). Although the overall composition of the three leaf transcriptomes was well-conserved, the gene expression patterns of particular gene ontology (GO) categories were notably different among the three accessions. Under non-submergence growing conditions, five protein categories (serine/threonine kinase, leucine-rich repeat kinase, signaling-related, glycoprotein, and glycosidase) were significantly (FDR, q < 0.05) enriched in up regulated DEGs from EC-SNU1. These up-regulated DEGs include major components of signal transduction pathways, such as receptor-like kinase (RLK) and calcium dependent protein kinase (CDPK) genes, as well as previously known abiotic stress responsive genes. Our results therefore suggest that diversified gene expression regulation of upstream signaling components conferred the molecular basis of adaptive diversity in Echinochloa crus-galli. PMID- 26266807 TI - Analytical Bias in the Measurement of Serum 25-Hydroxyvitamin D Concentrations Impairs Assessment of Vitamin D Status in Clinical and Research Settings. AB - Measured serum 25-hydroxyvitamin D concentrations vary depending on the type of assay used and the specific laboratory undertaking the analysis, impairing the accurate assessment of vitamin D status. We investigated differences in serum 25 hydroxyvitamin D concentrations measured at three laboratories (laboratories A and B using an assay based on liquid chromatography-tandem mass spectrometry and laboratory C using a DiaSorin Liaison assay), against a laboratory using an assay based on liquid chromatography-tandem mass spectrometry that is certified to the standard reference method developed by the National Institute of Standards and Technology and Ghent University (referred to as the 'certified laboratory'). Separate aliquots from the same original serum sample for a subset of 50 participants from the Ausimmune Study were analysed at the four laboratories. Bland-Altman plots were used to visually check agreement between each laboratory against the certified laboratory. Compared with the certified laboratory, serum 25-hydroxyvitamin D concentrations were on average 12.4 nmol/L higher at laboratory A (95% limits of agreement: -17.8,42.6); 12.8 nmol/L higher at laboratory B (95% limits of agreement: 0.8,24.8); and 10.6 nmol/L lower at laboratory C (95% limits of agreement: -48.4,27.1). The prevalence of vitamin D deficiency (defined here as 25-hydroxyvitamin D <50 nmol/L) was 24%, 16%, 12% and 41% at the certified laboratory, and laboratories A, B, and C, respectively. Our results demonstrate considerable differences in the measurement of 25 hydroxyvitamin D concentrations compared with a certified laboratory, even between laboratories using assays based on liquid chromatography-tandem mass spectrometry, which is often considered the gold-standard assay. To ensure accurate and reliable measurement of serum 25-hydroxyvitamin D concentrations, all laboratories should use an accuracy-based quality assurance system and, ideally, comply with international standardisation efforts. PMID- 26266808 TI - A Study of the Vaginal Microbiome in Healthy Canadian Women Utilizing cpn60-Based Molecular Profiling Reveals Distinct Gardnerella Subgroup Community State Types. AB - The vaginal microbiota is important in women's reproductive and overall health. However, the relationships between the structure, function and dynamics of this complex microbial community and health outcomes remain elusive. The objective of this study was to determine the phylogenetic range and abundance of prokaryotes in the vaginal microbiota of healthy, non-pregnant, ethnically diverse, reproductive-aged Canadian women. Socio-demographic, behavioural and clinical data were collected and vaginal swabs were analyzed from 310 women. Detailed profiles of their vaginal microbiomes were generated by pyrosequencing of the chaperonin-60 universal target. Six community state types (CST) were delineated by hierarchical clustering, including three Lactobacillus-dominated CST (L. crispatus, L. iners, L. jensenii), two Gardnerella-dominated (subgroups A and C) and an "intermediate" CST which included a small number of women with microbiomes dominated by seven other species or with no dominant species but minority populations of Streptococcus, Staphylococcus, Peptoniphilus, E. coli and various Proteobacteria in co-dominant communities. The striking correspondence between Nugent score and deep sequencing CST continues to reinforce the basic premise provided by the simpler Gram stain method, while additional analyses reveal detailed cpn60-based phylogeny and estimated abundance in microbial communities from vaginal samples. Ethnicity was the only demographic or clinical characteristic predicting CST, with differences in Asian and White women (p = 0.05). In conclusion, this study confirms previous work describing four cpn60 based subgroups of Gardnerella, revealing previously undescribed CST. The data describe the range of bacterial communities seen in Canadian women presenting with no specific vaginal health concerns, and provides an important baseline for future investigations of clinically important cohorts. PMID- 26266809 TI - Distinct Time Course of the Decrease in Hepatic AMP-Activated Protein Kinase and Akt Phosphorylation in Mice Fed a High Fat Diet. AB - AMP-activated protein kinase (AMPK) plays an important role in insulin resistance, which is characterized by the impairment of the insulin-Akt signaling pathway. However, the time course of the decrease in AMPK and Akt phosphorylation in the liver during the development of obesity and insulin resistance caused by feeding a high fat diet (HFD) remains controversial. Moreover, it is unclear whether the impairment of AMPK and Akt signaling pathways is reversible when changing from a HFD to a standard diet (SD). Male ddY mice were fed the SD or HFD for 3 to 28 days, or fed the HFD for 14 days, followed by the SD for 14 days. We examined the time course of the expression and phosphorylation levels of AMPK and Akt in the liver by immunoblotting. After 3 days of feeding on the HFD, mice gained body weight, resulting in an increased oil red O staining, indicative of hepatic lipid accumulation, and significantly decreased AMPK phosphorylation, in comparison with mice fed the SD. After 14 days on the HFD, systemic insulin resistance occurred and Akt phosphorylation significantly decreased. Subsequently, a change from the HFD to SD for 3 days, after 14 days on the HFD, ameliorated the impairment of AMPK and Akt phosphorylation and systemic insulin resistance. Our findings indicate that AMPK phosphorylation decreases early upon feeding a HFD and emphasizes the importance of prompt lifestyle modification for decreasing the risk of developing diabetes. PMID- 26266811 TI - Severe Rhabdomyolysis Associated with Staphylococcus aureus Acute Endocarditis Requiring Surgery. AB - BACKGROUND: Rhabdomyolysis has multiple etiologies with unclear mechanisms; however, rhabdomyolysis caused by Staphylococcus aureus infection is rare. CASE REPORT: A case report of severe rhabdomyolysis in a patient who presented with endocarditis caused by methicillin-susceptible S. aureus and review of relevant literature. RESULTS: The patient had a history of cardiac surgery for tetralogy of Fallot. He was admitted to the hospital because of fever and digestive symptoms. Respiratory and hemodynamic status deteriorated rapidly, leading to admission to the intensive care unit (ICU) for mechanical ventilation and vasopressor support. Laboratory tests disclosed severe rhabdomyolysis with a serum concentration of creatine kinase that peaked at 49,068 IU/L; all blood cultures grew methicillin-susceptible S. aureus. Antibiotic therapy was amoxicillin-clavulanic acid, ciprofloxacin, and gentamicin initially and was changed subsequently to oxacillin, clindamycin, and gentamicin. Transesophageal echocardiography showed vegetation on the pulmonary valve, thus confirming the diagnosis of acute endocarditis. Viral testing and computed tomography (CT) scan ruled out any obvious alternative etiology for rhabdomyolysis. Bacterial analysis did not reveal any specificity of the staphylococcal strain. The patient improved with antibiotics and was discharged from the ICU on day 26. He underwent redux surgery for valve replacement on day 53. CONCLUSIONS: Staphylococcal endocarditis should be suspected in cases of severe unexplained rhabdomyolysis with acute infectious symptoms. PMID- 26266810 TI - The PD-1/B7-H1 pathway modulates the natural killer cells versus mouse glioma stem cells. AB - PURPOSE: Glioblastoma multiforme (GBM) is the most malignant primary type of brain tumor in adults. There has been increased focus on the immunotherapies to treat GBM patients, the therapeutic value of natural killer (NK) cells is still unknown. Programmed death-1 (PD-1) is a major immunological checkpoint that can negatively regulate the T-cell-mediated immune response. We tested the combination of the inhibiting the PD-1/B7H1 pathway with a NK-cell mediated immune response in an orthotopic mouse model of GBM. METHODS AND MATERIALS: Mouse glioma stem cells (GL261GSCs) and mouse NK cells were isolated and identified. A lactate dehydrogenase (LDH) assay was perfomed to detect the cytotoxicity of NK cells against GL261GSCs. GL261GSCs were intracranially implanted into mice, and the mice were stratified into 3 treatment groups: 1) control, 2) NK cells treatment, and 3) PD-1 inhibited NK cells treatment group. Overall survival was quantified, and animal magnetic resonance imaging (MRI) was performed to determine tumor growth. The brains were harvested after the mice were euthanized, and immunohistochemistry against CD45 and PCNA was performed. RESULTS: The mouse NK cells were identified as 90% CD3- NK1.1+CD335+ by flow cytometric analysis. In the LDH assay, the ratios of the damaged GL261GSCs, with the E:T ratios of 2.5:1, 5:1, and 10:1, were as follows: 1) non-inhibited group: 7.42%, 11.31%, and 15.1%, 2) B7H1 inhibited group: 14.75%, 18.25% and 29.1%, 3) PD-1 inhibited group: 15.53%, 19.21% and 29.93%, 4) double inhibited group: 33.24%, 42.86% and 54.91%. In the in vivo experiments, the mice in the PD-1 inhibited NK cells treatment group and IL-2-stimulated-NK cells treatment group displayed a slowest tumor growth (F = 308.5, P<0.01) and a slower tumor growth compared with control group (F = 118.9, P<0.01), respectively. The median survival of the mice in the three groups were as follows: 1) conrol group: 29 days, 2) NK cells treatment group: 35 days (P = 0.0012), 3) PD-1 inhibited NK cells treatment group: 44 days (P = 0.0024). Immunologic data of PCNA-positive cell ratios and CD45-positive cell ratios of the tumor specimens in the three groups were as follows: 1) control group: 65.72% (PCNA) and 0.92% (CD45), 2) NK treatment group: 27.66% (PCNA) and 13.46% (CD45), and 3) PD-1 inhibited NK cells treatment group: 13.66% (PCNA) and 23.66% (CD45) (P<0.001). CONCLUSION: The results demonstrated that blockade of PD 1/B7H1 pathway could promote mouse NK cells to kill the GL261GSCs, and the PD-1 inhibited NK cells could be a feasible immune therapeutic approach against GBM. PMID- 26266812 TI - Recurrent desquamative vulvovaginitis in a young woman. PMID- 26266813 TI - Expression of PD-L1 on CD4+CD25+Foxp3+ Regulatory T Cells of Patients with Chronic HBV Infection and Its Correlation with Clinical Parameters. AB - Regulatory T cells (Tregs) play a pivotal role in suppressing specific antiviral immune responses during the progression of chronic hepatitis B virus infection (CHB) as well as tumorigenesis. Programmed death-1 ligand-1 (PD-L1) expressed on Tregs can transduce an inhibitory signal into effector T cells through interacting with programmed death-1 (PD-1). However, in CHB patients, the clinical significance of PD-L1 expression on Tregs has not been clearly described. This study investigated the frequency of circulating Tregs and PD-L1 expression on Tregs and analyzed their correlations with clinical parameters. The data show that both the frequency of CD4+CD25+FoxP3+ Tregs and PD-L1 expression on Tregs in the peripheral blood increased significantly in CHB patients when compared with healthy controls. At the same time, it is shown that PD-L1 expression on Tregs was positively correlated with the percentage of Tregs in CHB patients. Moreover, the results demonstrated that both Treg frequency and PD-L1 expression on Tregs positively correlated with the levels of alanine aminotransaminase (ALT) and aspartate aminotransferase (AST), both of which are indicators of the extent of liver injury. Taken together, these findings suggest that PD-L1 on Tregs might contribute to progression of hepatitis B virus infection through mediating the inhibitory function of Tregs. Thereby, blockade of interaction between Treg-expressing PD-L1 and PD-1 on effector T cells may be adopted as a potential therapeutic approach in CHB. PMID- 26266814 TI - Efficient Estimation of Mutation Rates during Individual Development by Minimization of Chi-Square. AB - Mutation primarily occurs when cells divide and it is highly desirable to have knowledge of the rate of mutations for each of the cell divisions during individual development. Recently, recessive lethal or nearly lethal mutations which were observed in a large mutation accumulation experiment using Drosophila melanogaster suggested that mutation rates vary significantly during the germline development of male Drosophila melanogaster. The analysis of the data was based on a combination of the maximum likelihood framework with numerical assistance from a newly developed coalescent algorithm. Although powerful, the likelihood based framework is computationally highly demanding which limited the scope of the inference. This paper presents a new estimation approach by minimizing chi square statistics which is asymptotically consistent with the maximum likelihood method. When only at most one mutation in a family is considered the minimization of chi-square is simplified to a constrained weighted minimum least square method which can be solved easily by optimization theory. The new methods effectively eliminates the computational bottleneck of the likelihood. Reanalysis of the published Drosophila melanogaster mutation data results in similar estimates of mutation rates. The new method is also expected to be applicable to the analysis of mutation data generated by next-generation sequencing technology. PMID- 26266815 TI - Correction: Biofilm Formation As a Response to Ecological Competition. PMID- 26266816 TI - Correction: Let-7, Mir-98 and Mir-181 as Biomarkers for Cancer and Schizophrenia. PMID- 26266818 TI - Effects of Immersion Solvent on Photovoltaic and Photophysical Properties of Porphyrin-Sensitized Solar Cells. AB - Memory effects in self-assembled monolayers (SAMs) of zinc porphyrin carboxylic acid on TiO2 electrodes have been demonstrated for the first time by evaluating the photovoltaic and electron transfer properties of porphyrin-sensitized solar cells prepared by using different immersion solvents sequentially. The structure of the SAM of the porphyrin on the TiO2 was maintained even after treating the porphyrin monolayer with different neat immersion solvents (memory effect), whereas it was altered by treatment with solutions containing different porphyrins (inverse memory effect). Infrared spectroscopy shows that the porphyrins in the SAM on the TiO2 could be exchanged with the same or analogous porphyrin, leading to a change in the structure of the porphyrin SAM. The memory and inverse memory effects are well correlated with a change in porphyrin geometry, mainly the tilt angle of the porphyrin along the long molecular axis from the surface normal on the TiO2, as well as with kinetics of electron transfer between the porphyrin and TiO2. Such a new structure-function relationship for DSSCs will be very useful for the rational design and optimization of photoelectrochemical and photovoltaic properties of molecular assemblies on semiconductor surfaces. PMID- 26266817 TI - SNAP23 Regulates Endothelial Exocytosis of von Willebrand Factor. AB - Endothelial exocytosis regulates vascular thrombosis and inflammation. The trafficking and release of endothelial vesicles is mediated by SNARE (Soluble NSF Attachment protein REceptors) molecules, but the exact identity of endothelial SNAREs has been unclear. Three SNARE molecules form a ternary complex, including isoforms of the syntaxin (STX), vesicle-associated membrane protein (VAMP), and synaptosomal-associated protein (SNAP) families. We now identify SNAP23 as the predominant endothelial SNAP isoform that mediates endothelial exocytosis of von Willebrand Factor (VWF). SNAP23 was localized to the plasma membrane. Knockdown of SNAP23 decreased endothelial exocytosis, suggesting it is important for endothelial exocytosis. SNAP23 interacted with the endothelial exocytic machinery, and formed complexes with other known endothelial SNARE molecules. Taken together, these data suggest that SNAP23 is a key component of the endothelial SNARE machinery that mediates endothelial exocytosis. PMID- 26266820 TI - The Nanoscale Basis of CO2 Trapping for Geologic Storage. AB - Carbon capture and storage (CCS) is likely to be a critical technology to achieve large reductions in global carbon emissions over the next century. Research on the subsurface storage of CO2 is aimed at reducing uncertainties in the efficacy of CO2 storage in sedimentary rock formations. Three key parameters that have a nanoscale basis and that contribute uncertainty to predictions of CO2 trapping are the vertical permeability kv of seals, the residual CO2 saturation Sg,r in reservoir rocks, and the reactive surface area ar of silicate minerals. This review summarizes recent progress and identifies outstanding research needs in these areas. Available data suggest that the permeability of shale and mudstone seals is heavily dependent on clay fraction and can be extremely low even in the presence of fractures. Investigations of residual CO2 trapping indicate that CO2 induced alteration in the wettability of mineral surfaces may significantly influence Sg,r. Ultimately, the rate and extent of CO2 conversion to mineral phases are uncertain due to a poor understanding of the kinetics of slow reactions between minerals and fluids. Rapidly improving characterization techniques using X-rays and neutrons, and computing capability for simulating chemical interactions, provide promise for important advances. PMID- 26266821 TI - A Population Health Perspective on Suicide Research and Prevention. PMID- 26266819 TI - Quantitative measurement of transmitters in individual vesicles in the cytoplasm of single cells with nanotip electrodes. AB - The quantification of vesicular transmitter content is important for studying the mechanisms of neurotransmission and malfunction in disease, and yet it is incredibly difficult to measure the tiny amounts of neurotransmitters in the attoliter volume of a single vesicle, especially in the cell environment. We introduce a novel method, intracellular vesicle electrochemical cytometry. A nanotip conical carbon-fiber microelectrode was used to electrochemically measure the total content of electroactive neurotransmitters in individual nanoscale vesicles in single PC12 cells as these vesicles lysed on the electrode inside the living cell. The results demonstrate that only a fraction of the quantal neurotransmitter content is released during exocytosis. These data support the intriguing hypothesis that the vesicle does not open all the way during the normal exocytosis process, thus resulting in incomplete expulsion of the vesicular contents. PMID- 26266823 TI - Ultrafast Dynamics of o-Nitrophenol: An Experimental and Theoretical Study. AB - The photolysis of o-nitrophenol (o-NP), a typical push-pull molecule, is of current interest in atmospheric chemistry as a possible source of nitrous acid (HONO). To characterize the largely unknown photolysis mechanism, the dynamics of the lowest lying excited singlet state (S1) of o-NP was investigated by means of femtosecond transient absorption spectroscopy in solution, time-resolved photoelectron spectroscopy (TRPES) in the gas phase and quantum chemical calculations. Evidence of the unstable aci-nitro isomer is provided both in the liquid and in the gas phase. Our results indicate that the S1 state displays strong charge transfer character, which triggers excited state proton transfer from the OH to the NO2 group as evidenced by a temporal shift of 20 fs of the onset of the photoelectron spectrum. The proton transfer itself is found to be coupled to an out-of-plane rotation of the newly formed HONO group, finally leading to a conical intersection between S1 and the ground state S0. In solution, return to S0 within 0.2-0.3 ps was monitored by stimulated emission. As a competitive relaxation channel, ultrafast intersystem crossing to the upper triplet manifold on a subpicosecond time scale occurs both in solution and in the gas phase. Due to the ultrafast singlet dynamics, we conclude that the much discussed HONO split-off is likely to take place in the triplet manifold. PMID- 26266825 TI - The Conundrum of Training in Global Surgery: Are We There Yet? PMID- 26266824 TI - Symmetry Controlled, Genetic Presentation of Bioactive Proteins on the P22 Virus like Particle Using an External Decoration Protein. AB - Viruses use spatial control of constituent proteins as a means of manipulating and evading host immune systems. Similarly, precise spatial control of proteins encapsulated or presented on designed nanoparticles has the potential to biomimetically amplify or shield biological interactions. Previously, we have shown the ability to encapsulate a wide range of guest proteins within the virus like particle (VLP) from Salmonella typhimurium bacteriophage P22, including antigenic proteins from human pathogens such as influenza. Expanding on this robust encapsulation strategy, we have used the trimeric decoration protein (Dec) from bacteriophage L as a means of controlled exterior presentation on the mature P22 VLP, to which it binds with high affinity. Through genetic fusion to the C terminus of the Dec protein, either the 17 kDa soluble region of murine CD40L or a minimal peptide designed from the binding region of the "self-marker" CD47 was independently presented on the P22 VLP capsid exterior. Both candidates retained function when presented as a Dec-fusion. Binding of the Dec domain to the P22 capsid was minimally changed across designed constructs, as measured by surface plasmon resonance, demonstrating the broad utility of this presentation strategy. Dec-mediated presentation offers a robust, modular means of decorating the exposed exterior of the P22 capsid in order to further orchestrate responses to internally functionalized VLPs within biological systems. PMID- 26266826 TI - Ulcerated plaque on the buttock of a nonagenarian woman. PMID- 26266827 TI - Role of B Cell-Activating Factor in Chronic Obstructive Pulmonary Disease. AB - RATIONALE: B cell-activating factor (BAFF) plays a major role in activation of B cells and in adaptive humoral immune responses. In chronic obstructive pulmonary disease (COPD), lymphoid follicles have been associated with disease severity, and overexpression of BAFF has been demonstrated within lymphoid follicles of patients with severe COPD. OBJECTIVES: To investigate expression and localization of BAFF in the lungs of patients with COPD and to study the role of BAFF in COPD by antagonizing BAFF in a mouse model of chronic cigarette smoke (CS) exposure. METHODS: We quantified and localized BAFF expression in lungs of never-smokers, smokers without COPD, and patients with COPD and in lungs of air- or CS-exposed mice by reverse-transcriptase polymerase chain reaction, ELISA, immunohistochemistry, and confocal imaging. Next, to investigate the role of BAFF in COPD, we antagonized BAFF by prophylactic or therapeutic administration of a soluble fusion protein of the BAFF-receptor, BAFFR-Fc, in mice exposed to air or CS for 24 weeks and evaluated several hallmarks of COPD and polarization of lung macrophages. MEASUREMENTS AND MAIN RESULTS: BAFF expression was significantly increased in lungs of patients with COPD and CS-exposed mice. BAFF staining in lymphoid follicles was observed around B cells, CD4(+) cells, dendritic cells, follicular dendritic cells, and fibroblastic reticular cells. Prophylactic and therapeutic administration of BAFFR-Fc in mice reduced pulmonary B-cell numbers and prevented CS-induced formation of lymphoid follicles and increases in immunoglobulin levels. Interestingly, prophylactic BAFFR-Fc administration significantly attenuated pulmonary inflammation and destruction of alveolar walls. Moreover, antagonizing BAFF altered the phenotype of alveolar and interstitial macrophages. CONCLUSIONS: BAFF is significantly increased in lungs of patients with COPD and is present around both immune and stromal cells within lymphoid follicles. Antagonizing BAFF in CS-exposed mice attenuates pulmonary inflammation and alveolar destruction. PMID- 26266828 TI - Liposomal formulation for co-delivery of paclitaxel and lapatinib, preparation, characterization and optimization. AB - Paclitaxel (PTX) is one of the most promising natural anticancer agents with a wide therapeutic range which is limited by its hydrophobic nature, low therapeutic index and more importantly, the emergence of multidrug resistance (MDR). Lapatinib (LPT) is a dual tyrosine kinase inhibitor with a significant potential to inhibit p-glycoproteins which form one of the main groups of proteins responsible for efflux pump mediated MDR. To overcome the PTX related MDR, a novel liposomal formulation was optimized for co-delivery of PTX and LPT by applying the D-optimal response surface methodology. The encapsulation efficiency (EE%) of the optimized formulation for LPT and PTX was 52 +/- 3% and 68 +/- 5, respectively. The optimized formulation showed a narrow size distribution with the average of 235 +/- 12 nm. The transmission electron microscopy image showed that liposomes were round in shape and discrete. The release profile exhibited 93% and 71% drug release for PTX and LPT after 40 h in the sink condition. The differential scanning calorimetry analysis indicated the conversion of both drugs from crystalline state to molecular state in the optimized lyophilized formulation. The cytotoxicity of the prepared formulation was studied against 4T1 murine mammary cells. The liposomal formulation showed better cytotoxicity in comparison to the binary mixture of free drugs. PMID- 26266829 TI - Long Distance Truck Drivers and the Structural Context of Health: A Culture Centered Investigation of Indian Truckers' Health Narratives. AB - Long-distance truck drivers (truckers) in India have been identified as a "high risk" group for the HIV/AIDS epidemic, and are consequently the targets of prevention and education-based interventions. While such interventions have addressed risk at the level of individual behavior, little attention has been paid to the structural barriers to health for truckers. Research among truckers in India has ignored the economic, social, and cultural context of health. In this article, I employ the culture-centered approach (CCA) to health communication in documenting truckers' narratives of health, which are innately connected to social and institutional structures around their lives. The data included 36 narrative interviews that I conducted as part of my fieldwork with Indian truckers, in addition to field notes and a reflexive journal. Through a reflexive analysis of these narratives, I present three themes: (a) the everyday violence of trucking, (b) health as sacrifice, and (c) migration and HIV/AIDS. I discuss how communication interventions can attend to the relationship between trucker health and the structural barriers they encounter. PMID- 26266830 TI - Reliability and Validity of Cutaneous Sarcoidosis Outcome Instruments Among Dermatologists, Pulmonologists, and Rheumatologists. AB - Importance: Dermatologists, pulmonologists, and rheumatologists study and treat patients with sarcoidosis with cutaneous manifestations. The validity of cutaneous sarcoidosis outcome instruments for use across medical specialties remains unknown. Objective: To assess the reliability and validity of cutaneous sarcoidosis outcome instruments for use by dermatologists and nondermatologists treating sarcoidosis. Design, Setting, and Participants: We performed a cross sectional study evaluating the use of the Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) and Sarcoidosis Activity and Severity Index (SASI) to assess cutaneous sarcoidosis disease severity and the Physician's Global Assessment (PGA) as a reference instrument. Four dermatologists, 3 pulmonologists, and 4 rheumatologists evaluated facial cutaneous sarcoidosis in 13 patients treated at a cutaneous sarcoidosis clinic in a 1-day study on October 24, 2014; data analysis was performed from November through December 2014. Main Outcomes and Measures: Interrater and intrarater reliability and convergent validity, with correlation with quality-of-life measures as the secondary outcome. Results: All instruments demonstrated excellent intrarater reliability. Interrater reliability (reported as intraclass correlation coefficient [95% CI]) was good for the CSAMI Activity scale (0.69 [0.51-0.87]) and PGA (0.66 [0.47 0.85]), weak for the CSAMI Damage scale (0.26 [0.11-0.52]), and excellent for the modified Facial SASI (0.78 [0.63-0.91]). The CSAMI Activity scale and modified Facial SASI showed moderate correlations (95% CI) with the PGA (0.67 [0.57-0.75] and 0.57 [0.45-0.66], respectively). The CSAMI Activity scale but not the modified Facial SASI showed significant correlations (95% CI) with quality-of life instruments, such as the Dermatology Life Quality Index (Spearman rank correlation, 0.70 [0.25-0.90]) and the Skin Stigma raw score of the Sarcoidosis Assessment Tool (Pearson product moment correlation, 0.56 [0.01-0.85]). Conclusions and Relevance: The CSAMI and SASI were reliable and valid in assessing cutaneous sarcoidosis among our diverse group of specialists. The CSAMI Activity score also correlated with quality-of-life measures and suggested construct validity. These results lend credibility to expand the use of the CSAMI and SASI by dermatologists and nondermatologists in assessing cutaneous sarcoidosis disease activity. PMID- 26266831 TI - The T-Box factor TBX3 is important in S-phase and is regulated by c-Myc and cyclin A-CDK2. AB - The transcription factor, TBX3, is critical for the formation of, among other structures, the heart, limbs and mammary glands and haploinsufficiency of the human TBX3 gene result in ulnar-mammary syndrome which is characterized by hypoplasia of these structures. On the other hand, the overexpression of TBX3 is a feature of a wide range of cancers and it has been implicated in several aspects of the oncogenic process. This includes its ability to function as an immortalizing gene and to promote proliferation through actively repressing negative cell cycle regulators. Together this suggests that TBX3 levels may need to be tightly regulated during the cell cycle. Here we demonstrate that this is indeed the case and that TBX3 mRNA and protein levels peak at S-phase and that the TBX3 protein is predominantly localized to the nucleus of S-phase cells. The increased levels of TBX3 in S-phase are shown to occur transcriptionally through activation by c-Myc at E-box motifs located at -1210 and -701 bps and post translationally by cyclin A-CDK2 phosphorylation. Importantly, when TBX3 is depleted by shRNA the cells accumulate in S-phase. These results suggest that TBX3 is required for cells to transit through S-phase and that this function may be linked to its role as a pro-proliferative factor. PMID- 26266832 TI - Biosilica-Entrapped Enzymes Studied by Using Dynamic Nuclear-Polarization Enhanced High-Field NMR Spectroscopy. AB - Enzymes are used as environmentally friendly catalysts in many industrial applications, and are frequently immobilized in a matrix to improve their chemical stability for long-term storage and reusability. Recently, it was shown that an atomic-level description of proteins immobilized in a biosilica matrix can be attained by examining their magic-angle spinning (MAS) NMR spectra. However, even though MAS NMR is an excellent tool for determining structure, it is severely hampered by sensitivity. In this work we provide the proof of principle that NMR characterization of biosilica-entrapped enzymes could be assisted by high-field dynamic nuclear polarization (DNP). PMID- 26266833 TI - Leveraging the Mechanism of Oxidative Decay for Adenylate Kinase to Design Structural and Functional Resistances. AB - Characterization of the mechanisms underlying hypohalous acid (i.e., hypochlorous acid or hypobromous acid) degradation of proteins is important for understanding how the immune system deactivates pathogens during infections and damages human tissues during inflammatory diseases. Proteins are particularly important hypohalous acid reaction targets in pathogens and in host tissues, as evidenced by the detection of chlorinated and brominated oxidizable residues. While a significant amount of work has been conducted for reactions of hypohalous acids with a range of individual amino acids and small peptides, the assessment of oxidative decay in full-length proteins has lagged in comparison. The most rigorous test of our understanding of oxidative decay of proteins is the rational redesign of proteins with conferred resistances to the decay of structure and function. Toward this end, in this study, we experimentally determined a putative mechanism of oxidative decay using adenylate kinase as the model system. In turn, we leveraged this mechanism to rationally design new proteins and experimentally test each system for oxidative resistance to loss of structure and function. From our extensive assessment of secondary structure, protein hydrodynamics, and enzyme activity upon hypochlorous acid or hypobromous acid challenge, we have identified two key strategies for conferring structural and functional resistance, namely, the design of proteins (adenylate kinase enzymes) that are resistant to oxidation requires complementary consideration of protein stability and the modification (elimination) of certain oxidizable residues proximal to catalytic sites. PMID- 26266834 TI - Peripheral natural killer cell and allo-stimulated T-cell function in kidney transplant recipients associate with cancer risk and immunosuppression-related complications. AB - Reducing immunosuppression has been proposed as a means of preventing cancer in kidney transplant recipients but this can precipitate graft rejection. Here we tested whether anti-tumor natural killer (NK) cell and allo-responsive T-cell function in kidney transplant recipients may predict cancer risk and define risk of rejection. NK cell function was measured by the release of lactate dehydrogenase and T-cell allo-response by interferon-gamma quantification using a panel of reactive T-cell enzyme-linked immunospot (ELISPOT) in 56 kidney transplant recipients with current or past cancer and 26 kidney transplant recipients without cancer. NK function was significantly impaired and the allo response was significantly lower in kidney transplant recipients with cancer. With prospective follow-up, kidney transplant recipients with poor NK cell function had a hazard ratio of 2.1 (95% confidence interval 0.97-5.00) for the combined end point of metastatic cancer, cancer-related death, or septic death. Kidney transplant recipients with low interferon-gamma release were also more likely to reach this combined end point. Thus, posttransplant monitoring of allo immunity and NK cell function is useful for assessing the risk of over immunosuppression for the development of malignancy and/or death from cancer or sepsis. PMID- 26266835 TI - Rapid, high-fluence multi-pass q-switched laser treatment of tattoos with a transparent perfluorodecalin-infused patch: A pilot study. AB - BACKGROUND AND OBJECTIVES: Perfluorodecalin (PFD) has previously been shown to rapidly dissipate the opaque, white micro-bubble layer formed after exposure of tattoos to Q-switched lasers [1]. The current pilot study was conducted to qualitatively determine if the use of a transparent PFD-infused silicone patch would result in more rapid clearance of tattoos than conventional through-air techniques. MATERIALS AND METHODS: Black or dark blue tattoos were divided into two halves in a single-site IRB-approved study with 17 subjects with Fitzpatrick skin types I-III. One half of each tattoo served as its own control and was treated with one pass of a standard Q-switched Alexandrite laser (755 nm). The other half of the tattoo was treated directly through a transparent perfluorodecalin (PFD) infused patch (ON Light Sciences, Dublin, CA). The rapid whitening reduction effect of the Patch routinely allowed three to four laser passes in a total of approximately 5 minutes. Both sides were treated at highest tolerated fluence, but the optical clearing, index-matching, and epidermal protection properties of the PFD Patch allowed significantly higher fluence compared to the control side. Standard photographs were taken at baseline, immediately prior to treatment with the PFD Patch in place, and finally before and after each treatment session. Treatments were administered at 4- to 6-week intervals. RESULTS: In a majority of subjects (11 of 17), tattoos treated through a transparent PFD-infused patch showed more rapid tattoo clearance with higher patient and clinician satisfaction than conventional treatment. In no case did the control side fade faster than the PFD Patch side. No unanticipated adverse events were observed. CONCLUSIONS: Rapid multi-pass treatment of tattoos with highest tolerated fluence facilitated by a transparent PFD-infused patch clears tattoos more rapidly than conventional methods. PMID- 26266836 TI - Low-temperature plasma ionization differential ion mobility spectrometry. AB - A low-temperature plasma (LTP) was used as an ionization source for differential ion mobility spectrometry (DMS) for the first time. This ionization source enhances the potential of DMS as a miniaturized system for on-site rapid monitoring. The effects of experimental parameters (e.g., discharge/carrier gas composition and flow rate, applied voltage) on the analysis of model aromatic compounds were investigated and discussed. It was found that the nature of reactant ion positive (RIP) is dependent on the discharge/carrier gas composition. The best response to the analyte was achieved when pure nitrogen was used as the discharge/carrier gas. The ability to perform analysis with zero helium consumption is especially attractive in view of the potential application of LTP-DMS for online (and on-site) monitoring. Analytical performance was determined with six environmentally relevant model compounds (benzene, toluene, ethylbenzene, p-xylene, 1,2,4-trimethylbenzene, and naphthalene) using LTP and directly compared to APPI and APCI ((63)Ni) ionization sources. When LTP was coupled to DMS, calculated LOD values were found to be in the range of 35-257 ng L(-1) (concentration in the carrier gas). These values are competitive with those calculated for two DMS equipped with traditional ionization sources (APPI, (63)Ni). The obtained results are promising enough to ensure the potential of LTP as ionization source for DMS. PMID- 26266837 TI - Investigation of the Binding Profiles of AZD2184 and Thioflavin T with Amyloid beta(1-42) Fibril by Molecular Docking and Molecular Dynamics Methods. AB - Detecting deposits of amyloid beta fibrils in the brain is of paramount importance for an early diagnosis of Alzheimer's disease. A number of PET tracers have been developed for amyloid imaging, but many suffer from poor specificity and large signal to background ratio. Design of tracers with specificity and improved binding affinity requires knowledge about various potential binding sites in the amyloid beta fibril available for the tracers and the nature of the local microenvironment of these sites. In this study we investigate the local structure of fibrils using two important probes, namely, thioflavin T (a fluorescent probe) and AZD2184 (a PET tracer). The target structures for amyloid beta(1-42) fibril are based on reported NMR solution models. By explicitly considering the effect of fibril flexibility on the available binding sites for all these models, the binding affinity of these probes has been investigated. The binding profiles of AZD2184 and thioflavin T were studied by molecular docking and molecular dynamics simulation methods. The two compounds were found to bind at the same sites of the fibril: three of which are within the fibril, and one is on the two sides of the Met35 residue on the surface. The binding affinity of AZD2184 and thioflavin T is found to be higher at the core sites than on the surface due to more contact residues. The binding affinity of AZD2184 is much higher than that of thioflavin T at every site due to electrostatic interaction and spatial restriction, which is in good agreement with experimental observation. However, the structural change of thioflavin T is much more significant than that of AZD2184, which is the chemical basis for its usage as a fluorescent probe. The ramifications of these results for the design and optimization of PET radioligands and fluorescent probes are briefly discussed. PMID- 26266839 TI - The Application of Chemical Derivatization in Forensic Drug Chemistry for Gas and High-Performance Liquid Chromatographic Methods of Analysis. AB - The analyses of solid-dosage forensic drug samples can be enhanced by chemical derivatization followed by gas chromatography or high-performance liquid chromatography. Using these techniques permits improved detection and chromatography of some illicit drugs and their manufacturing by-products. This review focuses on the use of chemical derivatization in conjunction with gas chromatography-flame ionization detection, gas chromatography-electron capture detection, gas chromatography-mass spectrometry, high-performance liquid chromatography-ultraviolet detection and high-performance liquid chromatography fluorescence detection in the analysis of illicit drug samples. These drugs include the amphetamines, barbiturates, cannabis, fentanyls, opium, and hallucinogens. Discussion on sensitivity enhancement and determination of enantiomeric composition using gas chromatography and high-performance liquid chromatography is included. An entire section is devoted to the chemical derivatization and chromatographic analyses of manufacturing by-products found in illicit amphetamine and methamphetamine, heroin, and cocaine samples. This review also includes a section that describes practical elements and experimental design associated with chemical derivatization-chromatographic analyses.. PMID- 26266838 TI - Predicting asthma morbidity in children using proposed markers of Th2-type inflammation. AB - BACKGROUND: Assessment of inflammation is becoming a common practice in the clinical work-up of children with persistent asthma. Biomarkers of Th2-mediated inflammation include blood eosinophils (B-Eos), exhaled nitric oxide (FeNO), total serum IgE (S-IgE), and serum periostin. The aim of this study was to investigate the associations between asthma morbidity and increased levels of these biomarkers in pediatric asthma. METHODS: School-age children (n = 96) with various manifestations of persistent asthma were included in this nationwide Swedish study. The protocol included the asthma control test, Juniper's quality of life questionnaire (QoL), assessment of pulmonary function, bronchial hyperresponsiveness, height-adjusted FeNO, blood sampling for S-IgE, B-Eos, and periostin, and high-resolution computed tomography (HRCT) of the lungs. RESULTS: Children with both high levels of height-adjusted FeNO and B-Eos were younger (p = 0.001), had more often severe asthma (p = 0.015), were more allergic (p < 0.001), had a reduced asthma control (p = 0.035), reduced QoL (p = 0.035), more exacerbations (p = 0.004), reduced FEV1/FVC (p = 0.001), and increased bronchial hyperresponsiveness (p < 0.001) as well as greater bronchial wall thickening on HRCT (p = 0.022) compared to those with low levels of both biomarkers. Grouping children according to high and low serum periostin levels did not relate to differences in clinical characteristics and biomarkers. CONCLUSIONS: Assessment of both local and systemic Th2-mediated inflammation by the analysis of easily attainable biomarkers such as exhaled NO and blood eosinophils has a high predictive value for the identification of children with the highest asthma morbidity. Adjusting FeNO values according to the individual child's height increases the clinical usefulness of this biomarker. PMID- 26266840 TI - Genetic Markers in Human Bone Tissue. AB - The use of genetic markers in bone and tissues as a method of human identification is reviewed in detail. Methods for the identification of human remains and the case situations requiring them are described. Some of the previous work on tissue and bone ABO grouping from both anthropological and medicolegal perspectives is reviewed; and some results from our own studies that have produced a highly reliable bone grouping procedure are presented. Some of our work and that of others on the typing of other classical genetic marker systems in bone is included. Recent work on DNA polymorphism typing and some actual and potential forensic applications of bone (and tissue) deoxyribonucleic acid (DNA) typing are discussed. PMID- 26266841 TI - Stability of Drugs of Abuse in Biological Specimens. AB - Knowledge about the stability of drugs in biological specimens is critical to proper interpretation of test results. Literature pertaining to the stability of drugs of abuse in blood, urine, saliva, and tissue specimens is reviewed in this article. Ethanol-related information are also included as it is an abused drug and its stability in blood and urine has been the subject of many studies. Other drug classes for which literature data were reviewed are barbiturates, benzodiazepines, cannabinoids, cocaine and benzoylecgonine, lysergic acid diethylamide, and phencyclidine. Stability characteristics for these drug classes depend on the drug, the specimen pH, and storage temperature. PMID- 26266843 TI - Understanding platelet dysfunction in sepsis. PMID- 26266844 TI - Electrochemical Barriers Made Simple. AB - A major challenge in the theoretical treatment of electrochemical charge transfer barriers is that simulations are performed at constant charge, which leads to dramatic potential shifts along the reaction path. Real electrochemical systems, however, operate at constant potential, which corresponds to a hypothetical model system of infinite size. Previous studies of hydrogen evolution have relied on a computationally costly scheme that extrapolates the barriers calculated on increasingly larger cells, and extension of this scheme to more complex reactions would be prohibitively costly. We present a new method to determine constant potential reaction energetics for simple charge transfer reactions that requires only (1) a single barrier calculation in an electrochemical environment and (2) the corresponding surface charge at the initial, transition, and final states. This method allows for a tremendous reduction in the computational resources required to determine electrochemical barriers and paves the way for a rigorous DFT-based kinetic analysis of electrochemical reactions beyond hydrogen evolution. PMID- 26266845 TI - Correction to "Two-Dimensional Metal Dichalcogenides and Oxides for Hydrogen Evolution: A Computational Screening Approach". PMID- 26266842 TI - Predictive value for weakness and 1-year mortality of screening electrophysiology tests in the ICU. AB - PURPOSE: Muscle weakness in long-stay ICU patients contributes to 1-year mortality. Whether electrophysiological screening is an alternative diagnostic tool in unconscious/uncooperative patients remains unknown. We aimed to determine the diagnostic properties of abnormal compound muscle action potential (CMAP), sensory nerve action potential (SNAP), and spontaneous electrical activity (SEA) for Medical Research Council (MRC)-defined weakness and their predictive value for 1-year mortality. METHODS: Data were prospectively collected during the EPaNIC trial (ClinicalTrials.gov: NCT00512122). First, sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of abnormal CMAP, SNAP, and SEA for weakness were determined. Subsequently, association between 1-year mortality and abnormal findings on electrophysiological screening was assessed by univariate and multivariate analyses correcting for weakness and other risk factors and the prediction model involved only a development phase. RESULTS: A total of 730 patients were electrophysiologically screened of whom 432 were tested for weakness. On day 8, normal CMAP excluded weakness with a high NPV (80.5 %). By day 15, abnormal SNAP and the presence of SEA had a high PPV (91.7 and 80.0 %, respectively). Only a reduced CMAP on day 8 was associated with higher 1-year mortality [35.6 vs 15.2 % (p < 0.001)]. This association remained significant after correction for weakness and other risk factors [OR 2.463 (95 % CI 1.113-5.452), p = 0.026]. Also among conscious/cooperative patients without weakness, reduced CMAP was independently associated with a higher likelihood of death occurring during 1 year [HR 2.818 (95 % CI 1.074-7.391), p = 0.035]. CONCLUSIONS: The diagnostic properties of electrophysiological screening vary over time. Abnormal CMAP documented early during critical illness carries information about longer-term outcome, which should be further investigated mechanistically. PMID- 26266846 TI - Ultrafast Hole Trapping and Relaxation Dynamics in p-Type CuS Nanodisks. AB - CuS nanocrystals are potential materials for developing low-cost solar energy conversion devices. Understanding the underlying dynamics of photoinduced carriers in CuS nanocrystals is essential to improve their performance in these devices. In this work, we investigated the photoinduced hole dynamics in CuS nanodisks (NDs) using the combination of transient optical (OTA) and X-ray (XTA) absorption spectroscopy. OTA results show that the broad transient absorption in the visible region is attributed to the photoinduced hot and trapped holes. The hole trapping process occurs on a subpicosecond time scale, followed by carrier recombination (~100 ps). The nature of the hole trapping sites, revealed by XTA, is characteristic of S or organic ligands on the surface of CuS NDs. These results not only suggest the possibility to control the hole dynamics by tuning the surface chemistry of CuS but also represent the first time observation of hole dynamics in semiconductor nanocrystals using XTA. PMID- 26266847 TI - High-Efficiency Polycrystalline Thin Film Tandem Solar Cells. AB - A promising way to enhance the efficiency of CIGS solar cells is by combining them with perovskite solar cells in tandem devices. However, so far, such tandem devices had limited efficiency due to challenges in developing NIR-transparent perovskite top cells, which allow photons with energy below the perovskite band gap to be transmitted to the bottom cell. Here, a process for the fabrication of NIR-transparent perovskite solar cells is presented, which enables power conversion efficiencies up to 12.1% combined with an average sub-band gap transmission of 71% for photons with wavelength between 800 and 1000 nm. The combination of a NIR-transparent perovskite top cell with a CIGS bottom cell enabled a tandem device with 19.5% efficiency, which is the highest reported efficiency for a polycrystalline thin film tandem solar cell. Future developments of perovskite/CIGS tandem devices are discussed and prospects for devices with efficiency toward and above 27% are given. PMID- 26266848 TI - Versatile Single-Layer Sodium Phosphidostannate(II): Strain-Tunable Electronic Structure, Excellent Mechanical Flexibility, and an Ideal Gap for Photovoltaics. AB - Density functional theory (DFT) calculations were performed to study the structural, mechanical, electrical, optical properties, and strain effects in single-layer sodium phosphidostannate(II) (NaSnP). We find the exfoliation of single-layer NaSnP from bulk form is highly feasible because the cleavage energy is comparable to graphite and MoS2. In addition, the breaking strain of the NaSnP monolayer is comparable to other widely studied 2D materials, indicating excellent mechanical flexibility of 2D NaSnP. Using the hybrid functional method, the calculated band gap of single-layer NaSnP is close to the ideal band gap of solar cell materials (1.5 eV), demonstrating great potential in future photovoltaic application. Furthermore, strain effect study shows that a moderate compression (2%) can trigger indirect-to-direct gap transition, which would enhance the ability of light absorption for the NaSnP monolayer. With sufficient compression (8%), the single-layer NaSnP can be tuned from semiconductor to metal, suggesting great applications in nanoelectronic devices based on strain engineering techniques. PMID- 26266849 TI - Charge-Transfer Dynamics of Fluorescent Dye-Sensitized Electrodes under Applied Biases. AB - The development of dye-sensitized solar cells requires an in-depth understanding of the interfacial charge-transfer dynamics that take place between dye sensitizers and semiconductors. Here, we describe a prototype system to probe these dynamics by monitoring in real time the fluorescence of two organic sensitizers, a perylene and a squaraine, bound to a SnO2 semiconductor thin film as a function of potentiostatic control of the Fermi level. The two different sensitizer fluorophores characterized by vastly different redox potentials undergo similar fluorescence modulation with applied bias, an indication that the density of states of the semiconductor largely influences the charge-transfer dynamics while energetics play a minimal role. We further show that the rate of photodegradation of the perylene sensitizer with applied bias provides a suitable marker to study the rate of charge injection and charge recombination. Taken together, our results demonstrate a suitable platform to visualize and study charge-transfer dynamics on films and constitute a step toward achieving single molecule resolution in our quest to decipher the static and dynamic heterogeneity of charge-transfer dynamics in dye-sensitized photoanodes. PMID- 26266850 TI - Vertical and Bidirectional Heterostructures from Graphyne and MSe2 (M = Mo, W). AB - Vertical and lateral heterostructures with atomically clean and sharp interfaces have opened up new realms in materials science, device physics and engineering. Herein, inspired by recent experiments, the unprecedented bidirectional heterostructures (BDHs) of gamma-graphyne@MoSe2/WSe2 as well as gamma graphyne@MoSe2 and gamma-graphyne@WSe2 are proposed and examined on the basis of first-principles calculations. Our results reveal that a novel wrinkled gamma graphyne with narrowed energy gap and strong binding strength is achieved on the planar and smooth substrate in gamma-graphyne@MoSe2/WSe2. The direct-indirect band gap crossover is also found in terms of interlayer coupling. Furthermore, we demonstrate that electron-hole pairs can be spatially separated, and the carrier mobility would be benefited from the absorbed gamma-graphyne in the BDHs. These results provide not only new insights into the physical and chemical properties of the vertical and bidirectional heterostructures, but also a new strategy for fabricating unprecedented 2D nanomaterials with exciting properties. PMID- 26266851 TI - Alternative Excitonic Structure in the Baseplate (BChl a-CsmA Complex) of the Chlorosome from Chlorobaculum tepidum. AB - In the photosynthetic green sulfur bacterium Chlorobaculum tepidum, the baseplate mediates excitation energy transfer from the light-harvesting chlorosome to the Fenna-Matthews-Olson (FMO) complex and subsequently toward the reaction center (RC). Literature data suggest that the baseplate is a 2D lattice of BChl a-CsmA dimers. However, recently, it has been proposed, using 2D electronic spectroscopy (2DES) at 77 K, that at least four excitonically coupled BChl a are in close contact within the baseplate structure [ Dostal , J. ; et al., J. Phys. Chem. Lett. 2014 , 5 , 1743 ]. This finding is tested via hole burning (HB) spectroscopy (5 K). Our results indicate that the four excitonic states identified by 2DES likely correspond to contamination of the baseplate with the FMO antenna and possibly the RC. In contrast, HB reveals a different excitonic structure of the baseplate chromophores, where excitation is transferred to a localized trap state near 818 nm via exciton hopping, which leads to emission near 826 nm. PMID- 26266852 TI - Strong Negative Temperature Dependence of the Simplest Criegee Intermediate CH2OO Reaction with Water Dimer. AB - The kinetics of the reaction of CH2OO with water vapor was measured directly with UV absorption at temperatures from 283 to 324 K. The observed CH2OO decay rate is second order with respect to the H2O concentration, indicating water dimer participates in the reaction. The rate coefficient of the CH2OO reaction with water dimer can be described by an Arrhenius expression k(T) = A exp(-Ea/RT) with an activation energy of -8.1 +/- 0.6 kcal mol(-1) and k(298 K) = (7.4 +/- 0.6) * 10(-12) cm(3) s(-1). Theoretical calculations yield a large negative temperature dependence consistent with the experimental results. The temperature dependence increases the effective loss rate for CH2OO by a factor of ~2.5 at 278 K and decreases by a factor of ~2 at 313 K relative to 298 K, suggesting that temperature is important for determining the impact of Criegee intermediate reactions with water in the atmosphere. PMID- 26266853 TI - Applicability of the Caldeira-Leggett Model to Vibrational Spectroscopy in Solution. AB - Formulating a rigorous system-bath partitioning approach remains an open issue. In this context, the famous Caldeira-Leggett model that enables quantum and classical treatment of Brownian motion on equal footing has enjoyed popularity. Although this model is by any means a useful theoretical tool, its ability to describe anharmonic dynamics of real systems is often taken for granted. In this Letter, we show that the mapping between a molecular system under study and the model cannot be established in a self-consistent way, unless the system part of the potential is taken effectively harmonic. Mathematically, this implies that the mapping is not invertible. This "invertibility problem" is not dependent on the peculiarities of particular molecular systems and is rooted in the anharmonicity of the system part of the Caldeira-Leggett model potential. PMID- 26266855 TI - Defects at the Two-Dimensional Limit. PMID- 26266854 TI - Hexagonal BC3: A Robust Electrode Material for Li, Na, and K Ion Batteries. AB - We have investigated the stability, maximum intercalation capacity, and voltage profile of alkali metal intercalated hexagonal BC3 (MxBC3), for 0 < x <= 2 and M = Li, Na, and K. Our calculations, based on dispersion-corrected density functional theory, show that these intercalation compounds are stable with respect to BC3 and their bulk metal counterparts. Moreover, we found that among all MxBC3 considered, the maximum stable capacity corresponds to an x value of 1.5, 1, and 1.5 for Li, Na, and K, respectively. These values are associated with large gravimetric capacities of 572 mA h/g for Na and 858 mA h/g for Li and K. Importantly, we show that metal intercalated hexagonal BC3 has the advantage of a small open-circuit voltage variation of approximately 0.49, 0.12, and 0.16 V for Li, Na, and K, respectively. Our results suggest that BC3 can become a robust alternative to graphitic electrodes in metal ion batteries, thus encouraging further experimental work. PMID- 26266856 TI - Flexoelectricity in Carbon Nanostructures: Nanotubes, Fullerenes, and Nanocones. AB - We report theoretical analysis of the electronic flexoelectric effect associated with nanostructures of sp(2) carbon (curved graphene). Through the density functional theory calculations, we establish the universality of the linear dependence of flexoelectric atomic dipole moments on local curvature in various carbon networks (carbon nanotubes, fullerenes with high and low symmetry, and nanocones). The usefulness of such dependence is in the possibility to extend the analysis of any carbon systems with local deformations with respect to their electronic properties. This result is exemplified by exploring of flexoelectric effect in carbon nanocones that display large dipole moment, cumulative over their surface yet surprisingly scaling exactly linearly with the length, and with sine-law dependence on the apex angle, dflex ~ L sin(alpha). Our study points out the opportunity of predicting the electric dipole moment distribution on complex graphene-based nanostructures based only on the local curvature information. PMID- 26266857 TI - Perovskite Solar Cells with Large-Area CVD-Graphene for Tandem Solar Cells. AB - Perovskite solar cells with transparent contacts may be used to compensate for thermalization losses of silicon solar cells in tandem devices. This offers a way to outreach stagnating efficiencies. However, perovskite top cells in tandem structures require contact layers with high electrical conductivity and optimal transparency. We address this challenge by implementing large-area graphene grown by chemical vapor deposition as a highly transparent electrode in perovskite solar cells, leading to identical charge collection efficiencies. Electrical performance of solar cells with a graphene-based contact reached those of solar cells with standard gold contacts. The optical transmission by far exceeds that of reference devices and amounts to 64.3% below the perovskite band gap. Finally, we demonstrate a four-terminal tandem device combining a high band gap graphene contacted perovskite top solar cell (Eg = 1.6 eV) with an amorphous/crystalline silicon bottom solar cell (Eg = 1.12 eV). PMID- 26266858 TI - What Is the Price of Open-Source Software? PMID- 26266859 TI - Negative Linear Compressibility in Organic Mineral Ammonium Oxalate Monohydrate with Hydrogen Bonding Wine-Rack Motifs. AB - Negative linear compressibility (NLC) is a relatively uncommon phenomenon and rarely studied in organic systems. Here we provide the direct evidence of the persistent NLC in organic mineral ammonium oxalate monohydrate under high pressure using synchrotron X-ray powder diffraction, Raman spectroscopy and density functional theory (DFT) calculation. Synchrotron X-ray powder diffraction measurement reveals that ammonium oxalate monohydrate shows both positive and negative linear compressibility along b-axis before 11.5 GPa. The red shift of the external Raman modes and abnormal changes of several selected internal modes in high-pressure Raman spectra further confirmed the NLC. DFT calculations demonstrate that the N-H...O hydrogen bonding "wine-rack" motifs result in the NLC along b-axis in ammonium oxalate monohydrate. We anticipate the high-pressure study of ammonium oxalate monohydrate may represent a promising strategy for accelerating the pace of exploitation and improvement of NLC materials especially in organic systems. PMID- 26266860 TI - Energy Transfer in Silicon Nanocrystal Solids Made from All-Inorganic Colloidal Silicon Nanocrystals. AB - Energy transfer between silicon (Si) nanocrystals (NCs) in Si-NC solids was demonstrated by photoluminescence (PL) spectroscopy. Clear differences of PL spectra and the decay rates between solutions and solids of Si-NCs were observed. The change in the PL properties caused by the formation of solids could be explained by the energy transfer from small to large NCs in the size distribution. In order to obtain further evidence of NC-to-NC energy transfer, the size distribution was intentionally modified by mixing solutions of NCs with different size distributions. NC solids made from the mixed solutions exhibited significantly different PL spectral shape and decay rates from those made from unmixed solutions, providing clear evidence of NC-to-NC energy transfer in Si-NC solids. PMID- 26266861 TI - Bringing Far-Field Subdiffraction Optical Imaging to Electronically Coupled Optoelectronic Molecular Materials Using Their Endogenous Chromophores. AB - We demonstrate that subdiffraction resolution can be achieved in fluorescence imaging of functional materials with densely packed, endogenous, electronically coupled chromophores by modifying stimulated emission depletion (STED) microscopy. This class of chromophores is not generally compatible with STED imaging due to strong two-photon absorption cross sections. Yet, we achieve 90 nm resolution and high contrast in images of clusters of conjugated polymer polyphenylenevinylene-derivative nanoparticles by modulating the excitation intensity in the material. This newfound capability has the potential to significantly broaden the range of fluorophores that can be employed in super resolution fluorescence imaging. Moreover, solution-processed optoelectronics and photosynthetic or other naturally luminescent biomaterials exhibit complex energy and charge transport characteristics and luminescence variations in response to nanoscale heterogeneity in their complex, physical structures. Our discovery will furthermore transform the current understanding of these materials' structure function relationships that have until now made them notoriously challenging to characterize on their native, subdiffraction scales. PMID- 26266862 TI - Modulation of the Hydrogen Bonding Structure of Water by Renal Osmolytes. AB - Osmolytes are an integral part of living organism, e.g., the kidney uses sorbitol, trimethylglycine, taurine and myo-inositol to counter the deleterious effects of urea and salt. Therefore, knowing that the osmolytes' act either directly to the protein or mediated through water is of great importance. Our experimental and computational results show that protecting osmolytes, e.g., trimethylglycine and sorbitol, significantly modulate the water H-bonding network structure, although the magnitude and spatial extent of osmolyte-induced perturbation greatly vary. In contrast, urea behaves neutrally toward local water H-bonding network. Protecting osmolytes studied here show strong concentration dependent behaviors (vibrational frequencies and lifetimes of two different infrared (IR) probes), while denaturant does not. The H-bond donor and/or acceptor (OH/NH) in a given osmolyte molecule play a critical role in defining their action. Our findings highlight the significance of the alteration of H bonding network of water under biologically relevant environment, often encountered in real biological systems. PMID- 26266863 TI - Tribochemical Decomposition of Light Ionic Hydrides at Room Temperature. AB - Tribochemical decomposition of magnesium hydride (MgH2) induced by deformation at room temperature was studied on a micrometric scale, in situ and in real time. During deformation, a near-full depletion of hydrogen in the micrometric affected zone is observed through an instantaneous (t < 1 s) and huge release of hydrogen (3-50 nmol/s). H release is related to a nonthermal decomposition process. After deformation, the remaining hydride is thermally decomposed at room temperature, exhibiting a much slower rate than during deformation. Confocal-microRaman spectroscopy of the mechanically affected zone was used to characterize the decomposition products. Decomposition was enhanced through the formation of the distorted structure of MgH2 with reduced crystal size by mechanical deformation. PMID- 26266864 TI - Same but Different: Dipole-Stabilized Shape Resonances in CuF(-) and AgF(.). AB - Electron attachment to closed-shell molecules is a gateway to various important processes in the gas and condensed phases. The properties of an electron-attached state, such as its energy and lifetime as well as the character of the molecular orbital to which the electron is attached, determine the fate of the anion. In this experimental and theoretical study of copper and silver fluoride anions, we introduce a new type of metastable anionic state. Abrupt changes in photoelectron angular distributions point to the existence of autodetaching states. Equation-of motion coupled-cluster singles and doubles calculations augmented by a complex absorbing potential identify some of these states as Sigma and Pi dipole stabilized resonances, a new type of shape resonance. In addition, these molecules support valence and dipole-bound states and a Sigma resonance of charge transfer character. By featuring five different types of anionic states, they provide a vehicle for studying fundamental properties of anions and for validating new theoretical approaches for metastable states. PMID- 26266865 TI - Phosphorene: Fabrication, Properties, and Applications. AB - Phosphorene, the single- or few-layer form of black phosphorus, was recently rediscovered as a two-dimensional layered material holding great promise for applications in electronics and optoelectronics. Research into its fundamental properties and device applications has since seen exponential growth. In this Perspective, we review recent progress in phosphorene research, touching upon topics on fabrication, properties, and applications; we also discuss challenges and future research directions. We highlight the intrinsically anisotropic electronic, transport, optoelectronic, thermoelectric, and mechanical properties of phosphorene resulting from its puckered structure in contrast to those of graphene and transition-metal dichalcogenides. The facile fabrication and novel properties of phosphorene have inspired design and demonstration of new nanodevices; however, further progress hinges on resolutions to technical obstructions like surface degradation effects and nonscalable fabrication techniques. We also briefly describe the latest developments of more sophisticated design concepts and implementation schemes that address some of the challenges in phosphorene research. It is expected that this fascinating material will continue to offer tremendous opportunities for research and development for the foreseeable future. PMID- 26266866 TI - Graphene-Based Membranes for Molecular Separation. AB - In comparison with traditional chemical separation processes, membrane separation is much simpler and more efficient. An ideal membrane for molecular separation should be as thin as possible to maximize its solvent flux, be mechanically robust to prevent it from fracture, and have well-defined pore sizes to guarantee its selectivity. Graphene is an excellent platform for developing size-selective membranes because of its atomic thickness, high mechanical strength, and chemical inertness. In this Perspective, we review the recent advancements on the fabrication of nanoporous graphene membranes and graphene oxide membranes (GOMs) for molecular separation. The methods of fabricating these membranes are summarized, and the mechanisms of molecular separation based on these two types of graphene membranes are compared. The challenges of synthesizing and transferring large-area nanoporous graphene membranes and engineering the performances of GOMs are discussed. PMID- 26266867 TI - Bright Fraction of Single-Walled Carbon Nanotubes through Correlated Fluorescence and Topography Measurements. AB - Correlated measurements of fluorescence and topography were performed for individual single-walled carbon nanotubes (SWNTs) on quartz using epifluorescence confocal microscopy and atomic force microscopy (AFM). Surprisingly, only ~11% of all SWNTs in DNA-wrapped samples were found to be highly emissive on quartz, suggesting that the ensemble fluorescence quantum yield is low because only a small population of SWNTs fluoresces strongly. Qualitatively similar conclusions were obtained from control studies using a sodium cholate surfactant system. To accommodate AFM measurements, excess surfactant was removed from the substrate. Though individual SWNTs on nonrinsed and rinsed surfaces displayed differences in fluorescence intensities and line widths, arising from the influence of the local environment on individual SWNT optical measurements, photoluminescence data from both samples displayed consistent trends. PMID- 26266868 TI - Dielectric Anomaly in Ice near 20 K: Evidence of Macroscopic Quantum Phenomena. AB - H2O is one of the most important substances needed in sustaining life; but not much is known about its ground state. Here a previously unidentified anomaly is identified in the form of a minimum in the imaginary part of the dielectric constant with respect to temperature near 20 K, while the real part remains monotonic. Isothermal dispersion and absorption measurements show coinciding results. For the case of heavy ice (D2O), no anomaly was identified, confirming an apparent isotope effect. Concerted quantum tunneling of protons is believed to be the main cause behind the reported anomaly. Our findings identify another system that exhibits macroscopic quantum phenomena that rarely occur in nature. PMID- 26266869 TI - Nd(3+)-Sensitized Ho(3+) Single-Band Red Upconversion Luminescence in Core-Shell Nanoarchitecture. AB - A strategy to achieve 808 nm excited single-band red upconversion luminescence of Ho(3+) via the core-shell nanoarchitecture design was provided. Specifically, the synthesized Yb/Ho/Ce: NaGdF4@Yb/Nd: NaYF4 active-core@active-shell nanoparticles were evidenced to enable high-content doping of Nd(3+) (~10 mol %) in the shell layer and, thus, markedly enhance red upconversion emission from Ho(3+) activators in the core with the assistance of spatially confined doping of Nd(3+) ions and efficient energy transfer of Nd(3+) -> Yb(3+)(shell) -> Yb(3+)(core) -> Ho(3+). Importantly, introducing Ce(3+) into the core was beneficial to the competition of radiation transitions from the two intermediate excited states of Ho(3+): (5)S2,(5)F4 (green-emitting) and Ho(3+): (5)F5 (red-emitting), which induced great enhancement in the red to green intensity ratio and ultimately intense single-band red upconversion emission. We believe that this preliminary study will provide an important advance in developing luminescent markers suitable for biolabeling applications. PMID- 26266870 TI - Temperature-Dependent Permeability of the Ligand Shell of PbS Quantum Dots Probed by Electron Transfer to Benzoquinone. AB - This paper describes an increase in the yield of collisionally gated photoinduced electron transfer (electron transfer events per collision) from oleate-capped PbS quantum dots (QDs) to benzoquinone (BQ) with increasing temperature (from 0 to 50 degrees C), due to increased permeability of the oleate adlayer of the QDs to BQ. The same changes in intermolecular structure of the adlayer that increase its permeability to BQ also increase its permeability to the solvent, toluene, resulting in a decrease in viscous drag and an apparent increase in the diffusion coefficient of the QDs, as measured by diffusion-ordered spectroscopy (DOSY) NMR. Comparison of NMR and transient absorption spectra of QDs capped with flexible oleate with those capped with rigid methylthiolate provides evidence that the temperature dependence of the permeability of the oleate ligand shell is due to formation of transient gaps in the adlayer through conformational fluctuations of the ligands. PMID- 26266871 TI - Ab Initio Study of BiFeO3: Thermodynamic Stability Conditions. AB - BiFeO3 is investigated intensively, mainly as a multiferroic material. In this paper, the state-of-the-art ab initio hybrid functional approach with atomic basis sets was employed for a study of the stability range of BiFeO3 with respect to its decomposition into binary oxides and elementary metals, as a function of temperature and oxygen partial pressure. The calculated atomic and electronic structure of BiFeO3 was compared with previous LDA+U calculations using plane wave basis sets. Based on performed calculations, the phase diagram was constructed, which allows us to predict the stability region of stoichiometric BiFeO3. PMID- 26266873 TI - Optical detection of glucose and glycated hemoglobin using etched fiber Bragg gratings coated with functionalized reduced graphene oxide. AB - An enhanced optical detection of D-glucose and glycated hemoglobin (HbA1c ) has been established in this study using etched fiber Bragg gratings (eFBG) coated with aminophenylboronic acid (APBA)-functionalized reduced graphene oxide (RGO). The read out, namely the shift in Bragg wavelength (DeltalambdaB ) is highly sensitive to changes that occur due to the adsorption of glucose (or HbA1c ) molecules on the eFBG sensor coated with APBA-RGO complex through a five-membered cyclic ester bond formation between glucose and APBA molecules. A limit of detection of 1 nM is achieved with a linear range of detection from 1 nM to 10 mM in the case of D-glucose detection experiments. For HbA1c , a linear range of detection varying from 86 nM to 0.23 mM is achieved. The observation of only 4 pm (picometer) change in DeltalambdaB even for the 10 mM lactose solution confirms the specificity of the APBA-RGO complex coated eFBG sensors to glucose molecules. PMID- 26266874 TI - PRESTO polarization transfer to quadrupolar nuclei: implications for dynamic nuclear polarization. AB - We show both experimentally and numerically on a series of model systems that in experiments involving transfer of magnetization from (1)H to the quadrupolar nuclei under magic-angle-spinning (MAS), the PRESTO technique consistently outperforms traditionally used cross polarization (CP), affording more quantitative intensities, improved lineshapes, better overall sensitivity, and straightforward optimization. This advantage derives from the fact that PRESTO circumvents the convoluted and uncooperative spin dynamics during the CP transfer under MAS, by replacing the spin-locking of quadrupolar nuclei with a single central transition selective 90 degrees pulse and using a symmetry-based recoupling sequence in the (1)H channel. This is of particular importance in the context of dynamic nuclear polarization (DNP) NMR of quadrupolar nuclei, where the efficient transfer of enhanced (1)H polarization is desired to obtain the highest sensitivity. PMID- 26266872 TI - New Insights into the Roles of Nogo-A in CNS Biology and Diseases. AB - Nogos have become a hot topic for its well-known number Nogo-A's big role in clinical matters. It has been recognized that the expression of Nogo-A and the receptor NgR1 inhibit the neuron's growth after CNS injuries or the onset of the MS. The piling evidence supports the notion that the Nogo-A is also involved in the synaptic plasticity, which was shown to negatively regulate the strength of synaptic transmission. The occurrence of significant schizophrenia-like behavioral phenotypes in Nogo-A KO rats also added strong proof to this conclusion. This review mainly focuses on the structure of Nogo-A and its corresponding receptor-NgR1, its intra- and extra-cellular signaling, together with its major physiological functions such as regulation of migration and distribution and its related diseases like stroke, AD, ALS and so on. PMID- 26266875 TI - Protein-protein interactions generate hidden feedback and feed-forward loops to trigger bistable switches, oscillations and biphasic dose-responses. AB - Protein-protein interactions (PPIs) defined as reversible association of two proteins to form a complex, are undoubtedly among the most common interaction motifs featured in cells. Recent large-scale proteomic studies have revealed an enormously complex interactome of the cell, consisting of tens of thousands of PPIs with numerous signalling hubs. PPIs have functional roles in regulating a wide range of cellular processes including signal transduction and post translational modifications, and de-regulation of PPIs is implicated in many diseases including cancers and neuro-degenerative disorders. Despite the ubiquitous appearance and physiological significance of PPIs, our understanding of the dynamic and functional consequences of these simple motifs remains incomplete, particularly when PPIs occur within large biochemical networks. We employ quantitative, dynamic modelling to computationally analyse salient dynamic features of the PPI motifs and PPI-containing signalling networks varying in topological architecture. Our analyses surprisingly reveal that simple reversible PPI motifs, when being embedded into signalling cascades, could give rise to extremely rich and complex regulatory dynamics in the absence of explicit positive and negative feedback loops. Our work represents a systematic investigation of the dynamic properties of PPIs in signalling networks, and the results shed light on how this simple event may potentiate diverse and intricate behaviours in vivo. PMID- 26266876 TI - On-chip surface modified nanostructured ZnO as functional pH sensors. AB - Zinc oxide (ZnO) nanostructures are promising candidates as electronic components for biological and chemical applications. In this study, ZnO ultra-fine nanowire (NW) and nanoflake (NF) hybrid structures have been prepared by Au-assisted chemical vapor deposition (CVD) under ambient pressure. Their surface morphology, lattice structures, and crystal orientation were investigated by scanning electron microscopy (SEM), x-ray diffraction (XRD), and transmission electron microscopy (TEM). Two types of ZnO nanostructures were successfully integrated as gate electrodes in extended-gate field-effect transistors (EGFETs). Due to the amphoteric properties of ZnO, such devices function as pH sensors. We found that the ultra-fine NWs, which were more than 50 MUm in length and less than 100 nm in diameter, performed better in the pH sensing process than NW-NF hybrid structures because of their higher surface-to-volume ratio, considering the Nernst equation and the Gouy-Chapman-Stern model. Furthermore, the surface coating of (3 Aminopropyl)triethoxysilane (APTES) protects ZnO nanostructures in both acidic and alkaline environments, thus enhancing the device stability and extending its pH sensing dynamic range. PMID- 26266878 TI - Genetic markers of recurrence in colorectal cancer. AB - Colorectal cancer (CRC) worldwide belongs to one of the most frequent cancers affecting both genders. Surgery and 5-fluorouracil-based adjuvant chemotherapy are recommended for patients with high-risk stage II and stage III colon carcinoma. Mutations of genes encoding for specific proteins may have an impact on the time to recurrence. These proteins act over specific signaling pathways, are implicated in metabolic processes and regulate the cell cycle. Though many retrospective studies show strong associations between genetic mutations and the clinical outcome of patients with CRC, currently no validated biomarkers are used in clinical routine settings. Therefore, large prospective validation studies should be carried out in order to strengthen the position of genetic mutations in personalized treatment of patients with CRC. PMID- 26266879 TI - Radiosurgery for mesial temporal lobe epilepsy. PMID- 26266877 TI - Ketamine for rapid reduction of suicidal ideation: a randomized controlled trial. AB - BACKGROUND: Suicide is a devastating public health problem and very few biological treatments have been found to be effective for quickly reducing the intensity of suicidal ideation (SI). We have previously shown that a single dose of ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, is associated with a rapid reduction in depressive symptom severity and SI in patients with treatment-resistant depression. METHOD: We conducted a randomized, controlled trial of ketamine in patients with mood and anxiety spectrum disorders who presented with clinically significant SI (n = 24). Patients received a single infusion of ketamine or midazolam (as an active placebo) in addition to standard of care. SI measured using the Beck Scale for Suicidal Ideation (BSI) 24 h post treatment represented the primary outcome. Secondary outcomes included the Montgomery-Asberg Depression Rating Scale--Suicidal Ideation (MADRS-SI) score at 24 h and additional measures beyond the 24-h time-point. RESULTS: The intervention was well tolerated and no dropouts occurred during the primary 7-day assessment period. BSI score was not different between the treatment groups at 24 h (p = 0.32); however, a significant difference emerged at 48 h (p = 0.047). MADRS-SI score was lower in the ketamine group compared to midazolam group at 24 h (p = 0.05). The treatment effect was no longer significant at the end of the 7 day assessment period. CONCLUSIONS: The current findings provide initial support for the safety and tolerability of ketamine as an intervention for SI in patients who are at elevated risk for suicidal behavior. Larger, well-powered studies are warranted. PMID- 26266880 TI - Abducent nerve palsy treated by microvascular decompression: a case report and review of the literature. AB - Too few cases of isolated abducent nerve palsy caused by neurovascular compression syndrome have been reported. We here report on a case of abducent nerve palsy caused by neurovascular compression syndrome that was successfully treated by microvascular decompression (MVD). A 46-year-old male presented with a 6-month history of right-sided persistent abducent nerve palsy. High-resolution magnetic resonance imaging revealed a neurovascular contact of the vertebral artery with the right abducent nerve. MVD was performed via a retrosigmoid craniotomy, with remarkable improvement of the palsy. Our report suggests that MVD might be considered as an optional treatment if the symptoms progress or persist. PMID- 26266881 TI - New Insights into the Conversion of Versicolorin A in the Biosynthesis of Aflatoxin B1. AB - A crucial and enigmatic step in the complex biosynthesis of aflatoxin B1 is the oxidative rearrangement of versicolorin A to demethylsterigmatocystin. This step is thought to proceed by an oxidation-reduction-oxidation sequence, in which the NADPH-dependent oxidoreductase AflM catalyzes the enclosed reduction step. AflM from Aspergillus parasiticus, after heterologous production in E. coli and purification, however, catalyzed the reduction of the hydroquinoid form of the starting compound versicolorin A (25% conversion) to a so far unknown product of aflatoxin biosynthesis. The asymmetric reduction of emodin hydroquinone to (R) 3,8,9,10-tetrahydroxy-6-methyl-3,4-dihydroanthracen-1(2H)-one (up to 82% for AflM) has also been observed in previous studies using MdpC from Aspergillus nidulans (monodictyphenone biosynthetic gene cluster). The first (nonenzymatic) reduction of emodin to emodin hydroquinone, for example with sodium dithionite, is obligatory for the enzymatic reduction by AflM or MdpC. These results imply an unprecedented role of AflM in the complex enzymatic network of aflatoxin biosynthesis. PMID- 26266882 TI - Testicular myxosporidiasis and ultrastructural characteristics of Myxobolus bufonis (Myxobolidae) infecting the Egyptian toad Bufo regularis (Bufonidae). A light and electron microscopic study. AB - The phylum Myxozoa comprises more than 2180 species, almost all of which are considered to be obligate parasites of aquatic fishes and amphibians. They are dangerous pathogens responsible for severe economic losses. From March to September 2014, 40 adult male Bufo regularis (Bufonidae) captured from different areas at Giza province, Egypt, were surveyed for myxosporean parasitic infection. Of these, 22 (55%) were infected by histozoic plasmodia, which produced spores after rupture belonging to Myxosporidia. The present investigation introduced a new data for the recorded parasite observed by light and transmission electron microscopy. The infection was diagnosed as large clusters of macroscopic plasmodia embedded in the testicular tissue causing distortion at the site of infection. The host reaction was manifested by the encapsulation of the plasmodia with a thick layer of connective tissue. Plasmodia were whitish in color, elliptical to ovoid in shape measuring 0.54 +/- 0.2 (0.34-0.63) mm in diameter. The spores were subspherical, reaching 7.1 +/- 0.2 (6.2-8.4) MUm in length and 6.3 +/- 0.2 (5.8-7.0) MUm in width with two equal-sized polar capsules regularly arranged at the anterior pole of each spore. They were 3.4 +/- 0.2 (3.0-4.2) MUm in length and 1.9 +/- 0.2 (1.6-2.4) in width with 6-8 turns of polar filaments. Ultrastructural analysis showed that the plasmodia were surrounded by a plasma membrane with numerous projections and pinocytotic channels extended toward the host cell. The generative cells and the different developmental stages were arranged at the periphery of the plasmodia while immature and mature spores were centrally arranged. Sporogenesis, capsulogenesis, valvogenesis, and spore maturation of the present parasite were also described. PMID- 26266883 TI - Development of a multiplex PCR for identification of Dictyocaulus lungworms in domestic and wild ruminants. AB - Dictyocaulus lungworms are the causative agents of parasitic bronchitis (dictyocaulosis) characterised by coughing and severe lung pathology in domestic and wild ruminants. The objective of this study was to design a simple molecular test that could detect of lungworm DNA from both adult and larval lungworms and could distinguish between the most common Dictyocaulus species found in cattle and in some species of wild ruminants. A multiplex PCR test with four novel primers targeting species-specific regions of the second internal transcribed spacer (ITS2) was designed based on our own sequence data as well as on available sequence information in GenBank. After PCR amplification of lungworms from European bison (Bison bonasus), cattle (Bos taurus), moose (Alces alces), red deer (Cervus elaphus) and roe deer (Capreolus capreolus), products were analysed with gel electrophoresis. This resulted in three specific bands of different size depending on the species analysed. Dictyocaulus viviparus collected from cattle or European bison resulted in a ca. 560 bp band, D. capreolus collected from roe deer produced a band ca. 400 bp and the longest DNA band (ca. 660 bp) was obtained with DNA from Dictyocaulus sp. collected from red deer and moose. Dictyocaulus eckerti bands with expected size of 714 bp were not observed in our study. The multiplex method produced consistent results with samples from both Sweden and Poland and overcame the limitations of traditional techniques based on differences in morphological features of parasites at different life stages. PMID- 26266884 TI - First acidic macro-mesocellular aluminosilicate monolithic foams "SiAl(HIPE)" and their catalytic properties. AB - A new type of acidic macrocellular and mesoporous silica-alumina foam is obtained via a one pot alkaline sol-gel route coupled with a concentrated emulsion-based templating technique. The mixed oxide monolith exhibits high surface acidity, translating into excellent performance in the acid-catalyzed dehydration of bioethanol to ethene. PMID- 26266885 TI - Concurrent use of strontium-89 with external beam radiotherapy for multiple bone metastases: early experience. AB - OBJECTIVE: The aim of the present study was to consider the safety and efficacy of concurrent use of strontium-89 (Sr-89) with external beam radiotherapy (EBRT) for multiple bone metastases, including lesions that require urgent therapy. METHODS: A retrospective review was performed of a consecutive series of patients who received Sr-89 for multiple bone metastases. Forty-five patients with multiple bone metastases received Sr-89 injection. Since 17 of the 45 patients had osteolytic bone lesions requiring emergent EBRT, they underwent concurrent use of Sr-89 with EBRT (concurrent group). The remaining 28 patients, none of whom had osteolytic lesions requiring urgent EBRT, were given Sr-89 injection only (singularity group). The injection of Sr-89 was to be given during EBRT, or on the day before the first day of EBRT. The dose of EBRT was 30 Gy in 10 fractions or 40 Gy in 20 fractions. Adverse events were evaluated according to hematological toxicity as measured by the Common Terminology Criteria for Adverse Events (V4.0). To assess efficacy, we checked changes in the pain scale and analgesic drug dosages, and the presence or absence of serious complications from bone metastases. RESULTS: Fifteen of 17 patients (88.2%) in the concurrent group and 17 of 28 patients (60.7%) in the singularity group reported bone pain relief. A statistically significant difference was found between the two groups, and severe complications (spinal cord compression and pathological fracture) from bone metastases could be prevented in all patients in the concurrent group. Severe hematological toxicity (grade 3 or higher) was not observed in the two groups. There was no statistical difference between the two groups. No one required additional intervention. The adverse events were tolerable. CONCLUSIONS: The results of our study suggest that concurrent use of Sr-89 with EBRT for multiple bone metastases can be performed safely if it is carried out with care, and that it may be an effective therapy in cases requiring emergency treatment. PMID- 26266886 TI - Patterns and Perceptions of Dextromethorphan Use in Adult Members of an Online Dextromethorphan Community. AB - Dextromethorphan (DXM) is a widely available antitussive that has, at elevated dose levels, euphoric and dissociative effects. This article presents the reported patterns and preferences of DXM use, and perceptions of DXM use among adult members of an online DXM community. Analyses were conducted of quantitative and qualitative responses from nine female and 43 male individuals, aged 18-63 years old. All respondents reported illegal and DXM drug use, beginning, on average, at 15.7 and 17.1 years of age, respectively. The majority of respondents first heard about DXM online or from a friend, preferred to use DXM alone, ingested substances concurrently with DXM to modify its effects, had not been to an emergency room or arrested because of their DXM use, and used DXM for its dissociative and mind-altering effects. DXM was perceived as safe and in no need of further regulation with only 14% of respondents mentioning DXM's addictive qualities. Findings from this sample of adult DXM users reveal a sophisticated subculture in which users report using DXM specifically to induce changes to their mental state and use a variety of substances to modify or enhance DXM's effects. PMID- 26266887 TI - Dosimetry of bone metastases in targeted radionuclide therapy with alpha-emitting (223)Ra-dichloride. AB - PURPOSE: Ra-dichloride is an alpha-emitting radiopharmaceutical used in the treatment of bone metastases from castration-resistant prostate cancer. Image based dosimetric studies remain challenging because the emitted photons are few. The aim of this study was to implement a methodology for in-vivo quantitative planar imaging, and to assess the absorbed dose to lesions using the MIRD approach. METHODS: The study included nine Caucasian patients with 24 lesions (6 humeral head lesions, 4 iliac wing lesions, 2 scapular lesions, 5 trochanter lesions, 3 vertebral lesions, 3 glenoid lesions, 1 coxofemoral lesion). The treatment consisted of six injections (one every 4 weeks) of 50 kBq per kg body weight. Gamma-camera calibrations for (223)Ra included measurements of sensitivity and transmission curves. Patients were statically imaged for 30 min, using an MEGP collimator, double-peak acquisition, and filtering to improve the image quality. Lesions were delineated on (99m)Tc-MDP whole-body images, and the ROIs superimposed on the (223)Ra images after image coregistration. The activity was quantified with background, attenuation, and scatter correction. Absorbed doses were assessed deriving the S values from the S factors for soft-tissue spheres of OLINDA/EXM, evaluating the lesion volumes by delineation on the CT images. RESULTS: In 12 lesions with a wash-in phase the biokinetics were assumed to be biexponential, and to be monoexponential in the remainder. The optimal timing for serial acquisitions was between 1 and 5 h, between 18 and 24 h, between 48 and 60 h, and between 7 and 15 days. The error in cumulated activity neglecting the wash-in phase was between 2 % and 12 %. The mean effective half life (T 1/2eff) of (223)Ra was 8.2 days (range 5.5-11.4 days). The absorbed dose (D) after the first injection was 0.7 Gy (range 0.2-1.9 Gy. Considering the relative biological effectiveness (RBE) of alpha particles (RBE = 5), D RBE = 899 mGy/MBq (range 340-2,450 mGy/MBq). The percent uptake of (99m)Tc and (223)Ra (activity extrapolated to t = 0) were significantly correlated. CONCLUSION: The feasibility of in vivo quantitative imaging in (223)Ra therapy was confirmed. The lesion uptake of (223)Ra-dichloride was significantly correlated with that of (99m)Tc-MDP. The D RBE to lesions per unit administered activity was much higher than that of other bone-seeking radiopharmaceuticals, but considering a standard administration of 21 MBq (six injections of 50 kBq/kg to a 70-kg patient), the mean cumulative value of D RBE was about 19 Gy, and was therefore in the range of those of other radiopharmaceuticals. The macrodosimetry of bone metastases in treatments with (223)Ra-dichloride is feasible, but more work is needed to demonstrate its helpfulness in predicting clinical outcomes. PMID- 26266888 TI - Accuracy of bone SPECT/CT for identifying hardware loosening in patients who underwent lumbar fusion with pedicle screws. AB - BACKGROUND: The aim of this retrospective study was to evaluate the accuracy of bone SPECT (single photon emission computed tomography)/CT (computed tomography) in diagnosing loosening of fixation material in patients with recurrent or persistent back pain that underwent lumbar arthrodesis with pedicle screws using surgery and clinical follow-up as gold standard METHODS: A total of 48 patients (median age 49 years, range 21-81 years; 17 men) who had undergone lumbar spinal arthrodesis were included in this retrospective analysis. SPECT/CT results were compared to the gold standard of surgical evaluation or clinical follow-up. Positive SPECT/CT results were considered true positives if findings were confirmed by surgery or if clinical and other examinations were completely consistent with the positive SPECT/CT finding. They were considered false positives if surgical evaluation did not find any loose pedicle screws or if symptoms subsided with non-surgical therapy. Negative SPECT/CT scans were considered true negatives if symptoms either improved without surgical intervention or remained stable over a minimum follow-up period of 6 months. Negative SPECT/CT scans were determined to be false negatives if surgery was still required and loosening of material was found. RESULTS: The median length of time from primary surgery to bone SPECT/CT referral was 29.5 months (range 12-192 months). Median follow-up was 18 months (range 6-57) for subjects who did not undergo surgery. Thirteen of the 48 patients were found to be positive for loosening on bone SPECT/CT. Surgical evaluation (8 patients) and clinical follow up (5 patients) showed that bone SPECT/CT correctly predicted loosening in 9 of 13 patients, while it falsely diagnosed loosening in 4 patients. Of 35 negative bone SPECT/CT scans, 12 were surgically confirmed. In 18 patients, bone SPECT/CT revealed lesions that could provide an alternative explanation for the symptoms of pain (active facet degeneration in 14 patients, and disc and sacroiliac osteodegeneration in 7 patients and 1 patient, respectively). Overall sensitivity and specificity for the detection of loosening were 100 % and 89.7 %, respectively. The positive and negative predictive values were 69 % and 100 %, respectively. CONCLUSIONS: This retrospective analysis suggests that bone SPECT/CT bone is a highly sensitive and specific tool for the exclusion of screw loosening in patients who present with recurrent low back pain after having undergone lumbar arthrodesis. In addition, it can identify other potential causes of recurrent low back pain in this patient population. PMID- 26266889 TI - Axonal Injury in Stroke: A Forensic Neuropathology Perspective. AB - The use of beta-amyloid precursor protein (beta-APP) immunocytochemistry is standard practice in forensic neuropathology to assess the presence and severity of traumatic axonal injury. However, axonal injury has many causes, in addition to trauma. The principal complicating factor in interpretation is where traumatic brain injury is associated with brain swelling or hemorrhage, resulting in ischemic axonal injury. Although it has been claimed that different patterns of beta-APP immunoreactivity are seen in trauma, as opposed to hypoxia-ischemia, there have been few systematic studies of beta-APP immunostaining patterns in ischemic or hemorrhagic stroke. This study investigated staining patterns in 96 cases of stroke with no history of head injury and found complex staining patterns, some of which were indistinguishable from those said to be specific for trauma. A questioning approach to the assessment of beta-APP immunostaining patterns in cases of head injury is proposed to ensure that the possibility of some or much of the staining being due to ischemia has been excluded, before concluding that the axonal injury identified is traumatic in causation. PMID- 26266890 TI - Sudden Death and Primary Leptomeningeal Melanocytosis: A Case Report With an Autopsy Diagnosis. AB - Meningeal melanocytoma is a rare benign pigmented tumor. It develops from melanocytes normally present in the meninges of the posterior fossa and medulla. It is an extra-axial tumor that manifests because of compression of adjacent structures. Although classified as a benign tumor, it can cause sudden death by several mechanisms. We report a rare case of meningeal melanocytoma and discuss the mechanism of death. A 21-year-old man with a previous history of recurrent lipothymia was admitted to the emergency department because of generalized seizures. Death occurred despite resuscitation. A medico-legal autopsy was performed. External examination of the body showed nonspecific asphyxia signs without any violence evidence. Necropsy noticed a brain edema with a dark color of the meninges especially in the frontal part. Histological examination concluded to diffuse meningeal melanocytoma with cerebral edema. PMID- 26266891 TI - A Fatal Case of Cervical Hemorrhage After Fine Needle Aspiration and Core Needle Biopsy of the Thyroid Gland. AB - Fine needle aspiration (FNA) and core needle biopsy (CNB) are recognized to be safe, useful, and inexpensive diagnostic tools for the evaluation of thyroid nodules. However, complications can arise during the procedure, albeit rarely and typically minor in nature. We report here an unusual fatal case of massive hematoma of the neck after FNA and CNB that may have caused airway obstruction. A 68-year-old Japanese woman underwent both procedures and was found dead at home later the same day. Although severe complications of FNA or CNB such as major bleeds or deaths are rarely reported, clinicians and forensic pathologists should be cognizant that complications can arise. PMID- 26266892 TI - A low-cost transcervical laryngeal injection trainer. AB - OBJECTIVES/HYPOTHESIS: To develop a low-cost, easy-to-construct model for education in transcervical laryngeal injection techniques. To validate the simulator among both fellowship-trained laryngologists and otolaryngology resident learners. STUDY DESIGN: Survey. METHODS: A transcervical laryngeal injection model was constructed. Fourteen otolaryngology residents used the model to practice vocal fold injection techniques. Survey feedback was obtained from all residents. RESULTS: Most learners agreed or strongly agreed that the simulator was easy to use (93%), was a good method to learn transcervical laryngeal injection technique (79%), improved their confidence with the procedure (78%), and could be applied to patients (72%). One hundred percent of the learners agreed or strongly agreed that they would recommend the simulator to other learners. CONCLUSION: Residents can be taught transcervical laryngeal injection techniques with a low-cost, easily constructed simulator prior to treating patients. This allows for a low-stress environment in which the learner can practice injection techniques. Resident feedback about the transcervical laryngeal injection simulator was very positive, including unanimous recommendation for use in other learners. LEVEL OF EVIDENCE: N/A. PMID- 26266893 TI - Effects of ECM protein micropatterns on the migration and differentiation of adult neural stem cells. AB - The migration and differentiation of adult neural stem cells (aNSCs) are believed to be strongly influenced by the spatial distribution of extracellular matrix (ECM) proteins in the stem cell niche. In vitro culture platform, which involves the specific spatial distribution of ECM protein, could offer novel tools for better understanding of aNSC behavior in the spatial pattern of ECM proteins. In this work, we applied soft-lithographic technique to design simple and reproducible laminin (LN)-polylysine cell culture substrates and investigated how aNSCs respond to the various spatial distribution of laminin, one of ECM proteins enriched in the aNSC niche. We found that aNSC preferred to migrate and attach to LN stripes, and aNSC-derived neurons and astrocytes showed significant difference in motility towards LN stripes. By changing the spacing of LN stripes, we were able to control the alignment of neurons and astrocytes. To the best of our knowledge, this is the first time to investigate the differential cellular responses of aNSCs on ECM protein (LN) and cell adhesive synthetic polymer (PDL) using surface micropatterns. Our findings would provide a deeper understanding in astrocyte-neuron interactions as well as ECM-stem cell interactions. PMID- 26266894 TI - Comparison between Monte Carlo simulation and measurement with a 3D polymer gel dosimeter for dose distributions in biological samples. AB - In this research, we used a 135 MeV/nucleon carbon-ion beam to irradiate a biological sample composed of fresh chicken meat and bones, which was placed in front of a PAGAT gel dosimeter, and compared the measured and simulated transverse-relaxation-rate (R2) distributions in the gel dosimeter. We experimentally measured the three-dimensional R2 distribution, which records the dose induced by particles penetrating the sample, by using magnetic resonance imaging. The obtained R2 distribution reflected the heterogeneity of the biological sample. We also conducted Monte Carlo simulations using the PHITS code by reconstructing the elemental composition of the biological sample from its computed tomography images while taking into account the dependence of the gel response on the linear energy transfer. The simulation reproduced the experimental distal edge structure of the R2 distribution with an accuracy under about 2 mm, which is approximately the same as the voxel size currently used in treatment planning. PMID- 26266895 TI - Melanoma survival: sex does matter, but we do not know how. AB - The objective of this study was to provide further insights into the prognostic role of female sex in skin melanoma. The prognostic effect of sex in a population based case series of 3900 skin melanomas in central Italy has been evaluated considering the possible confounding role of many demographic and clinical variables (age, period of diagnosis, Breslow's thickness, Clark level, ulceration, lymph node status, metastasis, histological type, skin site, and pathological T and N). Multiple imputations, according to chained equations, have been used for imputing incomplete values. A Cox proportional hazards model on the risk of death caused by melanoma was fitted. Univariate and multivariate effects of sex and of other variables were computed. The 5-year cause-specific survival was 87% (95% confidence interval: 86-89%) for women and 80% (78-82%) for men. Women had higher rates at any time since diagnosis. After adjustment for other confounders, women had a 34% reduced risk compared with men of dying from skin melanoma (hazard ratio=0.66, 95% confidence interval: 0.56-0.79). The present study confirmed a strong protective effect of female sex on skin melanoma mortality. The protective factor is still unknown. PMID- 26266896 TI - Addition of nitrite enhances the electrochemical defluorination of 2 fluoroaniline. AB - This study introduces a novel approach that uses the interaction of pollutants with added nitrite to produce diazonium salts, which cause in situ self-assembly of the pollutants on carbon electrodes, to improve their 2-fluoroaniline (2-FA) defluorination and removal performance. The 2-FA degradation performance, electrode properties, electrochemical properties and degradation pathway were investigated. The reactor containing NO2(-) achieved a 2-FA removal efficiency of 90.1% and a defluorination efficiency of 38% within 48 h, 1.4 and 2.3 times higher than the corresponding results achieved without NO2(-), respectively. The residual NO2(-) was less than 0.5mg/L in the reactor containing added NO2(-), which would not cause serious secondary pollution. Scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) results proved that the carbon anode surface was successfully modified with benzene polymer, and electrochemical tests confirmed that the electrochemical activity of the modified anode was enhanced significantly. The C-F bond was weakened by the effect of the positive charge of the benzenediazonium groups, and the high electrochemical activity of the carbon anode enhanced the electrochemical performance of the system to accelerate defluorination. Thus, the present electrical method involving nitrite nitrogen is very promising for the treatment of wastewater containing fluoroaniline compounds. PMID- 26266897 TI - Applying the Back-Propagation Neural Network model and fuzzy classification to evaluate the trophic status of a reservoir system. AB - The trophic state index, and in particular, the Carlson Trophic State Index (CTSI), is critical for evaluating reservoir water quality. Despite its common use in evaluating static water quality, the reliability of the CTSI may decrease when water turbidity is high. Therefore, this study examines the reliability of the CTSI and uses the Back-Propagation Neural Network (BPNN) model to create a new trophic state index. Fuzzy theory, rather than binary logic, is implemented to classify the trophic status into its three grades. The results show that compared to the CTSI with traditional classification, the new index with fuzzy classification can improve trophic status evaluation with high water turbidity. A reliable trophic state index can correctly describe reservoir water quality and allow relevant agencies to address proper water quality management strategies for a reservoir system. PMID- 26266898 TI - Integrating three tools for the environmental assessment of the Pardo River, Brazil. AB - There is a growing need for strategic assessment of environmental conditions in river basins around the world. In spite of the considerable water resources, Brazil has been suffering from water quality decrease in recent years. Pardo River runs through Minas Gerais and Sao Paulo, two of the most economically important states in Brazil, and is being currently promoted as a future drinking water source. This study aimed at integrating three different tools to conduct a hydromorphological assessment focused on the spatial complexity, connectivity, and dynamism of the Pardo River, Brazil. Twelve sampling stretches were evaluated in four sampling campaigns, in dry and rainy seasons. In each stretch, permanent preservation areas (PPAs), hydromorphological integrity by rapid assessment protocol (RAP), and physicochemical parameters were qualified. The kappa coefficient was used to assess statistical agreement among monitoring tools. The PPA analysis showed that in all stretches, the vegetation was modified. RAP results revealed environmental deterioration in stretches located near human activities and less variability of substrates available for aquatic fauna and sediment deposition as well. Low values for dissolved oxygen in the river mouth were noted in the rainy season. Electrical conductivity was higher in stretches near sugarcane crops. The poor agreement (k<0.35) between the RAP and physicochemical parameters indicates that the tools generate different and complementary information, while they are not replaceable. Potential changes of the hydromorphological characteristics and variations in physicochemical indicators must be related to extensive PPA modification. PMID- 26266899 TI - Occurrence and significance of polychlorinated biphenyls in water, sediment pore water and surface sediments of Umgeni River, KwaZulu-Natal, South Africa. AB - The Umgeni River is one of the main sources of water in KwaZulu-Natal, South Africa; however; there is currently a lack of information on the presence and distribution of polychlorinated biphenyls (PCBs) in its sediment, sediment pore water and surface water. This study aims to determine the occurrence and significance of selected PCBs in the surface water, sediment pore water and surface sediment samples from the Umgeni River. Liquid-liquid and soxhlet extractions were used for water or pore water, and sediments, respectively. Extracts were cleaned up using a florisil column and analysed by gas chromatography-mass spectrometry. The total concentrations of eight polychlorinated biphenyls were 6.91-21.69 ng/mL, 40.67-252.30 ng/mL and 102.60 427.80 ng/g (dry weight), in unfiltered surface water, unfiltered sediment pore water and surface sediments, respectively. The percentage contributions of various matrices were 4, 36 and 60 % for unfiltered surface water, unfiltered pore water and sediment, respectively. The highest concentrations of PCBs were found in water, pore water and sediment collected from sampling sites close to the Northern Wastewater Treatment Works. The highest chlorinated biphenyl, PCB 180, was the most abundant at almost all sampling sites. To our knowledge, this is the first report on occurrence of polychlorinated biphenyls in the Umgeni River water, pore water and sediment system and our results provide valuable information regarding the partitioning of the PCBs between the water and sediment systems as well as the organic chemical quality of the water. PMID- 26266901 TI - Adrenomedullin: its double-edged sword during sepsis slices yet again. PMID- 26266900 TI - Low expression of equilibrative nucleoside transporter 1 is associated with poor prognosis in chemotherapy-naive pT2 gallbladder adenocarcinoma patients. AB - AIMS: Equilibrative nucleoside transporter 1 (ENT1) is the major transporter of the chemotherapeutic drug gemcitabine, the current therapy for advanced gallbladder cancer (GBC). ENT1 expression has been proposed as a predictive marker for gemcitabine-treated pancreatic cancer patients. The aim of study was to explore the value of ENT1 measurement in chemotherapy-naive patients with advanced GBC. MATERIALS AND RESULTS: Immunohistochemistry for ENT1 was performed on 214 GBC samples from patients who had never undergone co-adjuvant or neo adjuvant chemotherapy. Advanced GBC cases were divided into groups with low or high ENT1 expression. Kaplan-Meier tests were used for survival analyses. The Cox regression method was used to assess the association of ENT1 expression with overall survival (OS). Low ENT1 expression was associated with younger patient age (P = 0.03) and moderate-to-poor histological differentiation (P = 0.01). pT2 patients with low ENT1 expression had shorter median survival (17.3 versus 28.7 months) and lower OS (17.3% versus 33.3%, P < 0.05) than patients with high ENT1 expression. Low ENT1 expression was an independent prognostic factor for OS (P = 0.036). CONCLUSIONS: ENT1 is a prognostic marker for pT2 GBC patients. Additional studies are needed to determine whether ENT1 has predictive value for gemcitabine response in GBC. PMID- 26266902 TI - Unilateral mechanical asymmetry: positional effects on lung volumes and transpulmonary pressure. AB - BACKGROUND: Ventilated patients with asymmetry of lung or chest wall mechanics may be vulnerable to differing lung stresses or strains dependent on body position. Our purpose was to examine transpulmonary pressure (P TP) and end expiratory lung volume (functional residual capacity (FRC)) during body positioning changes in an animal model under the influence of positive end expiratory pressure (PEEP) or experimental pleural effusion (PLEF). METHODS: Fourteen deeply anesthetized swine were studied including tracheostomy, thoracostomy, and esophageal catheter placement. Animals were ventilated at V T = 10 ml/kg, frequency of 15, I/E = 1:2, and FIO2 = 0.5. The animals were randomized to supine, prone, right lateral, left lateral, and semi-Fowler positions with a PEEP of 1 cm H2O (PEEP1) or a PEEP of 10 cm H2O (PEEP10) applied. Experimental PLEF was generated by 10 ml/kg saline instilled into either pleural space. P TP and FRC were determined in each condition. RESULTS: No significant differences in FRC were found among the four horizontal positions. Compared to horizontal positioning, semi-Fowler's increased FRC (p < 0.001) by 56% at PEEP1 and 54% at PEEP10 without PLEF and by 131% at PEEP1 and 98% at PEEP10 with PLEF. Inspiratory or expiratory P TP showed insignificant differences across positions at both levels of PEEP. Consistently negative end-expiratory P TP at PEEP1 increased to positive values with PEEP10. CONCLUSIONS: FRC did not differ among horizontal positions; however, semi-Fowler's positioning significantly raised FRC. P TP proved insensitive to mechanical asymmetry. While end-expiratory P TP was negative at PEEP1, applying PEEP10 caused a transition to positive P TP, suggestive of reopening of initially compressed lung units. PMID- 26266903 TI - A novel echocardiographic imaging technique, intracatheter echocardiography, to guide veno-venous extracorporeal membrane oxygenation cannulae placement in a validated ovine model. AB - BACKGROUND: Echocardiography plays a fundamental role in cannulae insertion and positioning for extracorporeal membrane oxygenation (ECMO). Optimal access and return cannulae orientation is required to prevent recirculation. The aim of this study was to compare a novel imaging technique, intracatheter echocardiography (iCATHe), with conventional intracardiac echocardiography (ICE) to guide placement of ECMO access and return venous cannulae. METHODS: Twenty sheep were commenced on veno-venous ECMO (VV ECMO). Access and return ECMO cannulae were positioned using an ICE-guided technique. Following the assessment of cannulae position, the ICE probe was then introduced inside the cannulae, noting location of the tip. After 24 h, the sheep were euthanized and cannulae position was determined at post mortem. The two-tailed McNemar test was used to compare iCATHe with ICE cannulae positioning. RESULTS: ICE and iCATHe imaging was possible in all 20 sheep commenced on ECMO. There was no significant difference between the two methods in assessing access cannula position (proportion correct for each 90%, incorrect 10%). However, there was a significant difference between ICE and iCATHe success rates for the return cannula (p = 0.001). Proportion correct for iCATHe and ICE was 80% and 15% respectively. iCATHe was 65% more successful (95% CI 27% to 75%) at predicting the placement of the return cannula. There were no complications related to the ICE or iCATHe imaging. CONCLUSION: iCATHe is a safe and feasible imaging technique to guide real-time VV ECMO cannulae placement and improves accuracy of return cannula positioning compared to ICE. PMID- 26266904 TI - Acute organ injury is associated with alterations in the cell-free plasma transcriptome. AB - BACKGROUND: Despite a genomic revolution in biological sciences, clinical medicine has yet to integrate diagnostics based upon gene expression into practice. While commonly used plasma protein assays rely on organ-specific origins, nearly all nucleic acid in whole blood is derived from white blood cells limiting their utility to diagnose non-immune disorders. The aim of the study was to use cell-free plasma to define circulating messenger RNA sequences diagnostic of acute organ injury, including myocardial infarction (MI) and acute kidney injury (AKI). METHODS: In healthy human subjects (N = 4) and patients with acute MI (N = 4), we characterized the concentration and nature of circulating plasma RNA through spectrophotometry and chromatography. Through reverse transcriptase polymerase chain reaction (RT-PCR) of amplicons up to 939 base pairs, we determined whether this mRNA was intact but of insufficient quantity to sequence. In mice, we induced an acute anterior myocardial infarction through 1 h of ischemia followed by reperfusion of the left anterior descending (LAD) artery. We compared the cell-free plasma transcriptome using cDNA microarray in sham operated mice compared to ischemia upon reperfusion and at 1 and 4 h. To determine organ specificity, we compared this profile to acute ischemia reperfusion of the kidney. RESULTS: In humans, there is more plasma RNA in those with acute MI than in healthy controls. In mice, ischemia-reperfusion of the LAD artery resulted in a time-dependent regulation of 589 circulating mRNA transcripts with less than a 5% overlap in sequences from acute ischemia reperfusion injury of the kidney. CONCLUSIONS: The mRNA derived from cell-free plasma defines organ injury in a time and injury-specific pattern. PMID- 26266905 TI - Bis maltolato oxovanadium (BMOV) and ischemia/reperfusion-induced acute kidney injury in rats. AB - BACKGROUND: The aim of the present study was to test the potential protective effects of the organic vanadium salt bis (maltolato) oxovanadium (BMOV; 15 mg/kg) in the context of renal ischemia/reperfusion (30 min of ischemia) and its effects on renal oxygenation and renal function in the acute phase of reperfusion (up to 90 min post-ischemia). METHODS: Ischemia was established in anesthetized and mechanically ventilated male Wistar rats by renal artery clamping. Renal microvascular and venous oxygenation were measured using phosphorimetry. Creatinine clearance rate, sodium reabsorption, and renal oxygen handling efficiency were considered markers for renal function. RESULTS: The main findings were that BMOV did not affect the systemic and renal hemodynamic and oxygenation variables and partially protected renal sodium reabsorption. CONCLUSIONS: Pretreatment with the organic vanadium compound BMOV did not protect the kidney from I/R injury. PMID- 26266906 TI - Administration of intrapulmonary sodium polyacrylate to induce lung injury for the development of a porcine model of early acute respiratory distress syndrome. AB - BACKGROUND: The loss of alveolar epithelial and endothelial integrity is a central component in acute respiratory distress syndrome (ARDS); however, experimental models investigating the mechanisms of epithelial injury are lacking. The purpose of the present study was to design and develop an experimental porcine model of ARDS by inducing lung injury with intrapulmonary administration of sodium polyacrylate (SPA). METHODS: The present study was performed at the Centre for Comparative Medicine, University of British Columbia, Vancouver, British Columbia. Human alveolar epithelial cells were cultured with several different concentrations of SPA; a bioluminescence technique was used to assess cell death associated with each concentration. In the anesthetized pig model (female Yorkshire X pigs (n = 14)), lung injury was caused in 11 animals (SPA group) by injecting sequential aliquots (5 mL) of 1% SPA gel in aqueous solution into the distal airway via a rubber catheter through an endotracheal tube. The SPA was dispersed throughout the lungs by manual bag ventilation. Three control animals (CON group) underwent all experimental procedures and measurements with the exception of SPA administration. RESULTS: The mean (+/- SD) ATP concentration after incubation of human alveolar epithelial cells with 0.1% SPA (0.92 +/- 0.27 MUM/well) was approximately 15% of the value found for the background control (6.30 +/- 0.37 MUM/well; p < 0.001). Elastance of the respiratory system (E RS) and the lung (E L) increased in SPA-treated animals after injury (p = 0.003 and p < 0.001, respectively). Chest wall elastance (E CW) did not change in SPA-treated animals. There were no differences in E RS, E L, or E CW in the CON group when pre- and post-injury values were compared. Analysis of bronchoalveolar lavage fluid showed a significant shift toward neutrophil predominance from before to after injury in SPA-treated animals (p < 0.001) but not in the CON group (p = 0.38). Necropsy revealed marked consolidation and congestion of the dorsal lung lobes in SPA-treated animals, with light-microscopy evidence of bronchiolar and alveolar spaces filled with neutrophilic infiltrate, proteinaceous debris, and fibrin deposition. These findings were absent in animals in the CON group. Electron microscopy of lung tissue from SPA-treated animals revealed injury to the alveolar epithelium and basement membranes, including intra-alveolar neutrophils and fibrin on the alveolar surface and intravascular fibrin (microthrombosis). CONCLUSIONS: In this particular porcine model, the nonimmunogenic polymer SPA caused a rapid exudative lung injury. This model may be useful to study ARDS caused by epithelial injury and inflammation. PMID- 26266907 TI - Uncontrolled sepsis: a systematic review of translational immunology studies in intensive care medicine. AB - BACKGROUND: The design of clinical immunology studies in sepsis presents several fundamental challenges to improving the translational understanding of pathologic mechanisms. We undertook a systematic review of bed-to-benchside studies to test the hypothesis that variable clinical design methodologies used to investigate immunologic function in sepsis contribute to apparently conflicting laboratory data, and identify potential alternatives that overcome various obstacles to improve experimental design. METHODS: We performed a systematic review of the design methodology employed to study neutrophil function (respiratory burst), monocyte endotoxin tolerance and lymphocyte apoptosis in the intensive care setting, over the past 15 years. We specifically focussed on how control samples were defined, taking into account age, gender, ethnicity, concomitant therapies, timing of sample collection and the criteria used to diagnose sepsis. RESULTS: We identified 57 eligible studies, the majority of which (74%) used case-control methodology. Healthy volunteers represented the control population selected in 83% of studies. Comprehensive demographic data on age, gender and ethnicity were provided in <=48% of case control studies. Documentation of diseases associated with immunosuppression, malignancy and immunomodulatory therapies was rare. Less than half (44%) of studies undertook independent adjudication for the diagnosis of sepsis while 68% provided microbiological data. The timing of sample collection was defined by highly variable clinical criteria. By contrast, surgical studies avoided many such confounders, although only one study in surgical patients monitored the study group for development of sepsis. CONCLUSIONS: We found several important and common limitations in the clinical design of translational immunologic studies in human sepsis. Major elective surgery overcame many of these methodological limitations. The failure of adequate clinical design in mechanistic studies may contribute to the lack of translational therapeutic progress in intensive care medicine. PMID- 26266908 TI - The effect of vitamin C on plasma volume in the early stage of sepsis in the rat. AB - BACKGROUND: Previous experimental studies have shown that vitamin C has several beneficial effects in sepsis and burns, such as decreased tissue oedema, improved endothelial barrier function and decreased transcapillary leakage of plasma markers. It has still not been investigated, though, if vitamin C has any impact specifically on plasma volume. The present study aims at testing the hypothesis that vitamin C decreases plasma volume loss in sepsis. METHODS: Anaesthetized male adult Sprague-Dawley rats were used in this prospective randomized study. All experiments were carried out at a university hospital laboratory. Sepsis was induced by caecal ligation and incision. After 3 h, vitamin C was given either as a bolus dose (66 mg/kg) followed by a continuous infusion (33 mg/kg/h) (n = 9), or as a single bolus dose (200 mg/kg) (n = 9). A sham group (n = 9) underwent the same surgical procedure, but no vitamin C was given. Plasma volume was measured ((125)I-dilution technique) at baseline, at 3 h after end of initiation of sepsis and at the end of the experiment 3 h later. Arterial blood samples for analyses of electrolytes, blood gases, haematocrit and lactate were taken at the same time points. RESULTS: There were no significant differences in plasma volumes or the physiological parameters analysed between any of the three groups at any time point. There was a significantly larger urine production in the single bolus dose group (200 mg/kg) compared to the sham group. CONCLUSIONS: Vitamin C treatment did not decrease the loss of plasma volume in the septic rat. The diuretic effect of vitamin C was in accordance with previous studies. PMID- 26266910 TI - Assessment of ventilation inhomogeneity during mechanical ventilation using a rapid-response oxygen sensor-based oxygen washout method. AB - PURPOSE: Ventilatory inhomogeneity indexes in critically ill mechanically ventilated patients could be of importance to optimize ventilator settings in order to reduce additional lung injury. The present study compared six inhomogeneity indexes calculated from the oxygen washout curves provided by the rapid oxygen sensor of the LUFU end-expiratory lung volume measurement system. METHODS: Inhomogeneity was tested in a porcine model before and after induction of acute lung injury (ALI) at four different levels of positive end-expiratory pressure (PEEP; 15, 10, 5 and 0 cm H2O). The following indexes were assessed: lung clearance index (LCI), mixing ratio, Becklake index, multiple breath alveolar mixing inefficiency, moment ratio and pulmonary clearance delay. RESULTS: LCI, mixing ratio, Becklake index and moment ratio were comparable with previous reported values and showed acceptable variation coefficients at baseline with and without ALI. Moment ratio had the highest precision, as calculated by the variation coefficients. LCI, Becklake index and moment ratio showed comparable increases in inhomogeneity during decremental PEEP steps before and after ALI. CONCLUSIONS: The advantage of the method we introduce is the combined measurement of end-expiratory lung volume (EELV) and inhomogeneity of lung ventilation with the LUFU fast-response medical-grade oxygen sensor, without the need for external tracer gases. This can be combined with conventional breathing systems. The moment ratio and LCI index appeared to be the most favourable for integration with oxygen washout curves as judged by high precision and agreement with previous reported findings. Studies are under way to evaluate the indexes in critically ill patients. PMID- 26266909 TI - Statins, fibrates, thiazolidinediones and resveratrol as adjunctive therapies in sepsis: could mitochondria be a common target? AB - Through their pleiotropic actions, statins, fibrates, thiazolidinediones and resveratrol can target multiple mechanisms involved in sepsis. Their actions on mitochondrial function are of interest in a pathological state where bioenergetic failure may play a key role in the development of organ dysfunction. We review these four drug groups as potential adjunctive therapies in sepsis with a particular focus upon mitochondria. Systematic review of clinical and experimental trials was done with a literature search using the PubMed database. Search terms included statins, fibrates, thiazolidinediones, resveratrol, mitochondria, sepsis, peroxisome proliferator-activated receptors, inflammation, oxidative stress and organ dysfunction. With the exception of statins, most of the compelling evidence for the use of these agents in sepsis comes from the experimental literature. The agents all exert anti-inflammatory and anti-oxidant properties, plus protective effects against mitochondrial dysfunction and stimulation of mitochondrial biogenesis. Improved outcomes (organ dysfunction, survival) have been reported in a variety of sepsis models. Notably, positive outcome effects were more commonly seen when the agents were given as pre- rather than post-treatment of sepsis. Statins, fibrates, thiazolidinediones and resveratrol prevent sepsis-induced injury to organs and organelles with outcome improvements. Their effects on mitochondrial function may be integral in offering this protection. Definitive clinical trials are needed to evaluate their utility in septic patients or those at high risk of developing sepsis. PMID- 26266911 TI - Reliability of the nitrogen washin-washout technique to assess end-expiratory lung volume at variable PEEP and tidal volumes. AB - BACKGROUND: End-expiratory lung volume measurement by the nitrogen washin-washout technique (EELVWI-WO) may help titrating positive end-expiratory pressure (PEEP) during acute respiratory distress syndrome (ARDS). Validation of this technique has been previously performed using computed tomography (EELVCT), but at mild PEEP levels, and relatively low fraction of inspired oxygen (FiO2), which may have insufficiently challenged the validity of this technique. The aims of this study were (1) to evaluate the reliability of EELVWI-WO measurements at different PEEP and V T during experimental ARDS and (2) to evaluate trending ability of EELVWI-WO to detect EELV changes over time. METHODS: ARDS was induced in 14 piglets by saline lavage. Optimal PEEP was selected during a decremental PEEP trial, based on best compliance, best EELVWI-WO, or a PEEP-FiO2 table. Eight V T (4 to 20 mL . kg(-1)) were finally applied at optimal PEEP. EELVWI-WO and EELVCT were determined after ARDS onset, at variable PEEP and V T. RESULTS: EELVWI-WO underestimated EELVCT with a non-constant linear bias, as it decreased with increasing EELV. Limits of agreement for bias were +/-398 mL. Bias between methods was greater at high PEEP, and further increased when high PEEP was combined with low V T. Concordance rate of EELV changes between consecutive measurements was fair (79%). Diagnostic accuracy was good for detection of absolute EELV changes above 200 mL (AUC = 0.79). CONCLUSIONS: The reliability of the WI-WO technique is critically dependent on ventilatory settings, but sufficient to accurately detect EELV change greater than 200 mL. PMID- 26266912 TI - Mechanical ventilation with heliox in an animal model of acute respiratory distress syndrome. AB - BACKGROUND: Heliox has a lower density and higher diffusion capacity compared to oxygen-in-air. We hypothesized that heliox ventilation allows for a reduction in minute volume ventilation and inspiratory pressures needed for adequate gas exchange in an animal model of an acute lung injury. METHODS: After intratracheal instillation of lipopolysaccharide (10 mg/kg), adult rats were randomized to ventilation with either a gas mixture of helium/oxygen (50:50%) or oxygen/air (50:50%). They were mechanically ventilated according to the ARDSnet recommendations with tidal volumes of 6 ml/kg and monitored with a pneumotachometer. Bronchoalveolar lavage fluid was analyzed for markers of lung injury, and embedded lung sections were histologically scored for lung injury. RESULTS: Heliox limited the increase in driving pressures needed to achieve preset tidal volumes, with a concomitant decrease in loss of compliance. Heliox did neither allow for reduced minute volume ventilation in this model nor improve gas exchange. Also, heliox did not reduce lung injury. CONCLUSIONS: Heliox modestly improved respiratory mechanics but did not improve lung injury in this rat model of acute respiratory distress syndrome. PMID- 26266913 TI - A standardized model of brain death, donor treatment, and lung transplantation for studies on organ preservation and reconditioning. AB - BACKGROUND: We set a model of brain death, donor management, and lung transplantation for studies on lung preservation and reconditioning before transplantation. METHODS: Ten pigs (39.7 +/- 5.9 Kg) were investigated. Five animals underwent brain death and were treated as organ donors; the lungs were then procured and cold stored (Ischemia). Five recipients underwent left lung transplantation and post-reperfusion follow-up (Graft). Cardiorespiratory and metabolic parameters were collected. Lung gene expression of cytokines (tumor necrosis factor alpha (TNFalpha), interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), interferon gamma (IFNgamma), high mobility group box-1 (HMGB-1)), chemokines (chemokine CC motif ligand-2 (CCL2-MCP-1), chemokine CXC motif ligand 10 (CXCL-10), interleukin-8 (IL-8)), and endothelial activation markers (endothelin-1 (EDN-1), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), selectin-E (SELE)) was assessed by real-time polymerase chain reaction (PCR). RESULTS: Tachycardia and hypertension occurred during brain death induction; cardiac output rose, systemic vascular resistance dropped (P < 0.05), and diabetes insipidus occurred. Lung-protective ventilation strategy was applied: 9 h after brain death induction, PaO2 was 192 +/- 12 mmHg at positive end-expiratory pressure (PEEP) 8.0 +/- 1.8 cmH2O and FiO2 of 40%; wet to-dry ratio (W/D) was 5.8 +/- 0.5, and extravascular lung water (EVLW) was 359 +/- 80 mL. Procured lungs were cold-stored for 471 +/- 24 min (Ischemia) at the end of which W/D was 6.1 +/- 0.9. Left lungs were transplanted and reperfused (warm ischemia 98 +/- 14 min). Six hours after controlled reperfusion, PaO2 was 192 +/- 23 mmHg (PEEP 8.7 +/- 1.5 cmH2O, FiO2 40%), W/D was 5.6 +/- 0.4, and EVLW was 366 +/- 117 mL. Levels of IL-8 rose at the end of donor management (BD, P < 0.05); CCL2-MCP-1, IL-8, HMGB-1, and SELE were significantly altered after reperfusion (Graft, P < 0.05). CONCLUSIONS: We have set a standardized, reproducible pig model resembling the entire process of organ donation that may be used as a platform to test in vivo and ex vivo strategies of donor lung optimization before transplantation. PMID- 26266914 TI - Moderately high frequency ventilation with a conventional ventilator allows reduction of tidal volume without increasing mean airway pressure. AB - BACKGROUND: The aim of this study was to explore if positive-pressure ventilation delivered by a conventional ICU ventilator at a moderately high frequency (HFPPV) allows a safe reduction of tidal volume (V T) below 6 mL/kg in a porcine model of severe acute respiratory distress syndrome (ARDS) and at a lower mean airway pressure than high-frequency oscillatory ventilation (HFOV). METHODS: This is a prospective study. In eight pigs (median weight 34 [29,36] kg), ARDS was induced by pulmonary lavage and injurious ventilation. The animals were ventilated with a randomized sequence of respiratory rates: 30, 60, 90, 120, 150, followed by HFOV at 5 Hz. At each step, V T was adjusted to allow partial pressure of arterial carbon dioxide (PaCO2) to stabilize between 57 and 63 mmHg. Data are shown as median [P25th,P75th]. RESULTS: After lung injury, the PaO2/FiO2 (P/F) ratio was 92 [63,118] mmHg, pulmonary shunt 26 [17,31]%, and static compliance 11 [8,14] mL/cmH2O. Positive end-expiratory pressure (PEEP) was 14 [10,17] cmH2O. At 30 breaths/min, V T was higher than 6 (7.5 [6.8,10.2]) mL/kg, but at all higher frequencies, V T could be reduced and PaCO2 maintained, leading to reductions in plateau pressures and driving pressures. For frequencies of 60 to 150/min, V T progressively fell from 5.2 [5.1,5.9] to 3.8 [3.7,4.2] mL/kg (p < 0.001). There were no detrimental effects in terms of lung mechanics, auto-PEEP generation, hemodynamics, or gas exchange. Mean airway pressure was maintained constant and was increased only during HFOV. CONCLUSIONS: During protective mechanical ventilation, HFPPV delivered by a conventional ventilator in a severe ARDS swine model safely allows further tidal volume reductions. This strategy also allowed decreasing airway pressures while maintaining stable PaCO2 levels. PMID- 26266915 TI - Genetic and pharmacologic inhibition of Tpl2 kinase is protective in a mouse model of ventilator-induced lung injury. AB - BACKGROUND: Mechanical stress induced by injurious ventilation leads to pro inflammatory cytokine production and lung injury. The extracellular-signal regulated-kinase, ERK1/2, participates in the signaling pathways activated upon mechanical stress in the lungs to promote the inflammatory response. Tumor progression locus 2 (Tpl2) is a MAP3kinase that activates ERK1/2 upon cytokine or TLR signaling, to induce pro-inflammatory cytokine production. The role of Tpl2 in lung inflammation, and specifically in the one caused by mechanical stress has not been investigated. The aim of the study was to examine if genetic or pharmacologic inhibition of Tpl2 could ameliorate ventilator-induced lung injury. METHODS: Adult male wild-type and Tpl2-deficient mice were ventilated with normal or high tidal volume for 4 h. Additional wild-type mice were treated with a Tpl2 inhibitor either before or 30 min after initiation of high tidal ventilation. Non ventilated mice of both genotypes served as controls. The development of lung injury was evaluated by measuring lung mechanics, arterial blood gases, concentrations of proteins, IL-6, and MIP-2 in bronchoalveolar lavage fluid (BALF) and by lung histology. Data were compared by Kruskal-Wallis non-parametric test and significance was defined as p < 0.05. RESULTS: Mechanical ventilation with normal tidal volume induced a mild increase of IL-6 in BALF in both strains. High tidal volume ventilation induced lung injury in wild-type mice, characterized by decreased lung compliance, increased concentrations of proteins, IL-6 and MIP-2 in BALF, and inflammatory cell infiltration on histology. All indices of lung injury were ameliorated in Tpl2-deficient mice. Wild-type mice treated with the Tpl2 inhibitor, either prior of after the initiation of high tidal volume ventilation were protected from the development of lung injury, as indicated by preserved lung compliance and lower BALF concentrations of proteins and IL-6, than similarly ventilated, untreated wild-type mice. CONCLUSIONS: Genetic and pharmacologic inhibition of Tpl2 is protective in a mouse model of ventilator-induced lung injury, ameliorating both high-permeability pulmonary edema and lung inflammation. PMID- 26266916 TI - Relevance of induced and accidental hypothermia after trauma-haemorrhage-what do we know from experimental models in pigs? AB - Recent experimental research has either focused on the role of accidental hypothermia as part of the lethal triad after trauma or tried to elucidate the effects of therapeutically induced hypothermia on the posttraumatic course. Induced hypothermia seems to reduce the mortality in experimental models of trauma-haemorrhage. As potential mechanisms, a decrease of cellular metabolism, beneficial effects on haemodynamic function and an attenuation of the inflammatory response have been described. However, negative side effects of hypothermia have to be considered, such as impairment of the coagulatory function and immunosuppressive effects. Furthermore, the optimal strategy for the induction of hypothermia (magnitude, duration, timing, cooling rate, etc.) and subsequent rewarming remains unclear. Nevertheless, this piece of information is essential before considering hypothermia as a treatment strategy for severely injured patients. This review aims to elaborate the differences between accidental and induced hypothermia and to summarize the current knowledge of the potential therapeutic use of induced hypothermia suggested in porcine models of trauma-haemorrhage. PMID- 26266917 TI - Regulation of lung oxidative damage by endogenous superoxide dismutase in sepsis. AB - BACKGROUND: The purpose of this research is to study the relationship between superoxide dismutase (SOD) and lung redox state in an animal model of sepsis. METHODS: Sepsis was induced in rats by the cecal ligation and perforation model (CLP). After 3, 6, and 12 h, CLP protein content and expression of SOD1, SOD2, and SOD3 were evaluated, and SOD activity was assessed. Oxidative damage was determined by quantifying nitrotyrosine content. Lung localization of SOD3 was performed by immunohistochemistry. The protective effect of a SOD mimetic on oxidative damage, inflammation, and lung permeability was assessed 12 and 24 h after sepsis induction. RESULTS: Lung levels of SOD1 decreased 3 and 12 h after sepsis, but SOD2 and SOD3 increased, as well as SOD activity. These alterations were not associated with changes in sod gene expression. Nitrotyrosine levels increased 3 and 12 h after sepsis. The administration of a SOD mimetic decreased nitrotyrosine and proinflammatory cytokine levels and improved lung permeability. CONCLUSIONS: SOD2 and SOD3 increased after sepsis induction, but this was insufficient to protect the lung. Treatments based on SOD mimetics could have a role in lung injury associated with sepsis. PMID- 26266918 TI - 'Chronomics' in ICU: circadian aspects of immune response and therapeutic perspectives in the critically ill. AB - Complex interrelations exist between the master central clock, located in the suprachiasmatic nuclei of the hypothalamus, and several peripheral clocks, such as those found in different immune cells of the body. Moreover, external factors that are called 'timekeepers', such as light/dark and sleep/wake cycles, interact with internal clocks by synchronizing their different oscillation phases. Chronobiology is the science that studies biologic rhythms exhibiting recurrent cyclic behavior. Circadian rhythms have a duration of approximately 24 h and can be assessed through chronobiologic analysis of time series of melatonin, cortisol, and temperature. Critically ill patients experience severe circadian deregulation due to not only the lack of effective timekeepers in the intensive care unit (ICU) environment but also systemic inflammation. The latter has been found in both animal and human studies to disrupt circadian rhythmicity of all measured biomarkers. The aims of this article are to describe circadian physiology during acute stress and to discuss the effects of ICU milieu upon circadian rhythms, in order to emphasize the value of considering circadian immune disturbance as a potential tool for personalized treatment. Thus, besides neoplastic processes, critical illness could be linked to what has been referred as 'chronomics': timing and rhythm. In addition, different therapeutic perspectives will be presented in association with environmental approaches that could restore circadian connection and hasten physical recovery. PMID- 26266919 TI - Effects of glycemic control on glucose utilization and mitochondrial respiration during resuscitated murine septic shock. AB - BACKGROUND: This study aims to test the hypothesis whether lowering glycemia improves mitochondrial function and thereby attenuates apoptotic cell death during resuscitated murine septic shock. METHODS: Immediately and 6 h after cecal ligation and puncture (CLP), mice randomly received either vehicle or the anti diabetic drug EMD008 (100 MUg . g(-1)). At 15 h post CLP, mice were anesthetized, mechanically ventilated, instrumented and rendered normo- or hyperglycemic (target glycemia 100 +/- 20 and 180 +/- 50 mg . dL(-1), respectively) by infusing stable, non-radioactive isotope-labeled (13)C6-glucose. Target hemodynamics was achieved by colloid fluid resuscitation and continuous i.v. noradrenaline, and mechanical ventilation was titrated according to blood gases and pulmonary compliance measurements. Gluconeogenesis and glucose oxidation were derived from blood and expiratory glucose and (13)CO2 isotope enrichments, respectively; mathematical modeling allowed analyzing isotope data for glucose uptake as a function of glycemia. Postmortem liver tissue was analyzed for HO-1, AMPK, caspase-3, and Bax (western blotting) expression as well as for mitochondrial respiratory activity (high-resolution respirometry). RESULTS: Hyperglycemia lowered mitochondrial respiratory capacity; EMD008 treatment was associated with increased mitochondrial respiration. Hyperglycemia decreased AMPK phosphorylation, and EMD008 attenuated both this effect as well as the expression of activated caspase-3 and Bax. During hyperglycemia EMD008 increased HO-1 expression. During hyperglycemia, maximal mitochondrial oxidative phosphorylation rate was directly related to HO-1 expression, while it was unrelated to AMPK activation. According to the mathematical modeling, EMD008 increased the slope of glucose uptake plotted as a function of glycemia. CONCLUSIONS: During resuscitated, polymicrobial, murine septic shock, glycemic control either by reducing glucose infusion rates or EMD008 improved glucose uptake and thereby liver tissue mitochondrial respiratory activity. EMD008 effects were more pronounced during hyperglycemia and coincided with attenuated markers of apoptosis. The effects of glucose control were at least in part due to the up regulation of HO-1 and activation of AMPK. PMID- 26266920 TI - Can computer simulators accurately represent the pathophysiology of individual COPD patients? AB - BACKGROUND: Computer simulation models could play a key role in developing novel therapeutic strategies for patients with chronic obstructive pulmonary disease (COPD) if they can be shown to accurately represent the pathophysiological characteristics of individual patients. METHODS: We evaluated the capability of a computational simulator to reproduce the heterogeneous effects of COPD on alveolar mechanics as captured in a number of different patient datasets. RESULTS: Our results show that accurately representing the pathophysiology of individual COPD patients necessitates the use of simulation models with large numbers (up to 200) of compartments for gas exchange. The tuning of such complex simulation models 'by hand' to match patient data is not feasible, and thus we present an automated approach based on the use of global optimization algorithms and high-performance computing. Using this approach, we are able to achieve extremely close matches between the simulator and a range of patient data including PaO2, PaCO2, pulmonary deadspace fraction, pulmonary shunt fraction, and ventilation/perfusion (/Q) curves. Using the simulator, we computed combinations of ventilator settings that optimally manage the trade-off between ensuring adequate gas exchange and minimizing the risk of ventilator-associated lung injury for an individual COPD patient. CONCLUSIONS: Our results significantly strengthen the credibility of computer simulation models as research tools for the development of novel management protocols in COPD and other pulmonary disease states. PMID- 26266921 TI - Brain function in iNOS knock out or iNOS inhibited (l-NIL) mice under endotoxic shock. AB - BACKGROUND: Microcirculatory dysfunction due to excessive nitric oxide production by the inducible nitric oxide synthase (iNOS) is often seen as a motor of sepsis related organ dysfunction. Thus, blocking iNOS may improve organ function. Here, we investigated neuronal functional integrity in iNOS knock out (-/-) or l-NIL treated wild-type (wt) animals in an endotoxic shock model. METHODS: Four groups of each 10 male mice (28 to 32 g) were studied: wt, wt + lipopolysaccharide (LPS) (5 mg/kg body weight i.v.), iNOS(-/-) + LPS, wt + LPS + l-NIL (5 mg/kg body weight i.p. 30 min before LPS). Electric forepaw stimulation was performed before LPS/vehicle and then at fixed time points repeatedly up to 4.5 h. N1-P1 potential amplitudes as well as P1 latencies were calculated from EEG recordings. Additionally, cerebral blood flow was registered using laser Doppler. Blood gas parameters, mean arterial blood pressure, and glucose and lactate levels were obtained at the beginning and the end of experiments. Moreover, plasma IL-6, IL 10, CXCL-5, ICAM-1, neuron-specific enolase (NSE), and nitrate/nitrite levels were determined. RESULTS: Decline in blood pressure, occurrence of cerebral hyperemia, acidosis, and increase in lactate levels were prevented in both iNOS blocked groups. SEP amplitudes and NSE levels remained in the range of controls. Effects were related to a blocked nitrate/nitrite level increase whereas IL-6, ICAM-1, and IL-10 were similarly induced in all sepsis groups. Only CXCL-5 induction was lower in both iNOS-blocked groups. CONCLUSIONS: Despite similar hyper-inflammatory responses, iNOS inhibition strategies appeared neurofunctionally protective possibly by stabilizing macro- as well as microcirculation. Overall, our data support modern sepsis guidelines recommending early prevention of microcirculatory failure. PMID- 26266922 TI - Effect of PEEP on breath sound power spectra in experimental lung injury. AB - BACKGROUND: Acute lung injury (ALI) is known to be associated with the emergence of inspiratory crackles and enhanced transmission of artificial sounds from the airway opening to the chest wall. Recently, we described the effect of ALI on the basic flow-induced breath sounds, separated from the crackles. In this study, we investigated the effects of positive end-expiratory pressure (PEEP) on these noncrackling basic lung sounds augmented during ALI. METHODS: Lung sounds were recorded in six anesthetized, intubated, and mechanically ventilated pigs at three locations bilaterally on the chest wall. Recordings were obtained before and after induction of lung injury with oleic acid and during application of incremental positive end-expiratory pressure. RESULTS: Oleic acid injections caused severe pulmonary edema predominately in the dependent-lung regions. Inspiratory spectral power of breath sounds increased in all lung regions over a frequency band from 150 to 1,200 Hz, with further power augmentation in dependent lung areas at higher frequencies. Incremental positive end-expiratory pressure reversed the spectral power augmentation seen with ALI, reducing it to pre-injury levels with PEEP of 10 and 15 cmH2O in all lung regions at all frequencies. The application of positive end-expiratory pressure to normal lungs attenuated spectral power slightly and only over a band from 150 to 1,200 Hz. CONCLUSIONS: We confirm a gravity-related spectral amplitude increase of basic flow-induced breath sounds recorded over lung regions affected by permeability-type pulmonary edema and show that such changes are reversible by alveolar recruitment with PEEP. PMID- 26266923 TI - The renal compartment: a hydraulic view. AB - BACKGROUND: The hydraulic behavior of the renal compartment is poorly understood. In particular, the role of the renal capsule on the intrarenal pressure has not been thoroughly addressed to date. We hypothesized that pressure and volume in the renal compartment are not linearly related, similar to other body compartments. METHODS: The pressure-volume curve of the renal compartment was obtained by injecting fluid into the renal pelvis and recording the rise in intrarenal pressure in six anesthetized and mechanically ventilated piglets, using a catheter Camino 4B(r) inserted into the renal parenchyma. RESULTS: In healthy kidneys, pressure has a highly nonlinear dependence on the injected volume, as revealed by an exponential fit to the data (R (2) = 0.92). On the contrary, a linear relation between pressure and volume is observed in decapsulated kidneys. We propose a biomechanical model for the renal capsule that is able to explain the nonlinear pressure-volume dependence for moderate volume increases. CONCLUSIONS: We have presented experimental evidence and a theoretical model that supports the existence of a renal compartment. The mechanical role of the renal capsule investigated in this work may have important implications in elucidating the role of decompressive capsulotomy in reducing the intrarenal pressure in acutely injured kidneys. PMID- 26266924 TI - A simple and easy in vitro model to test the efficacy of IV lines' needleless connectors against contamination. AB - BACKGROUND: Hub colonization after manipulation is responsible for 29% to 60% of catheter-related bloodstream infections (C-RBSI). Prevention can be achieved by the use of hub connectors, but its efficacy is generally based on instillation of high concentrations of microorganisms, which do not reflect the real contamination in daily practice. Our purpose was to create an in vitro model lasting long enough to be used for the comparison of the efficacy between various connectors against contamination simulating the real daily handling. METHODS: The model consisted of 40 blood culture bottles with an inserted cannula with a needle-free closed connector. Twice a day, each line was manipulated while instilling 1 mL of two different fluids (saline and propofol). We manipulated the bottles as follows: ten bottles with clean gloves and disinfecting connectors with alcohol (controls), ten bottles with hands (no gloves), ten bottles with gloves impregnated with a 0.5 McFarland (MF) solution of Staphylococcus aureus (SA), and ten bottles with gloves impregnated with a 0.05 MF solution of SA. The bottles were incubated in a BACTEC System at 37 degrees C under continuous agitation up to 10 days. When a bottle turned positive, 100 MUL of the fluid was cultured and incubated followed by microorganism identification using standard procedures. RESULTS: Overall, all bottles in the control group were negative at the end of the incubation time. In the three contamination experiments, almost all (38/40) bottles were positive during the incubation time. We only found differences regarding the median time to positivity (interquartile range (IQR)) between saline and propofol in the manipulation with SA 0.05 MF: 240 h (154.82 to 360.00) vs. 66 h (58.01 to 69.11), p = 0.008. CONCLUSIONS: A daily connector handling with 0.05 McFarland S. aureus solution while instilling saline proved to be a useful model lasting long enough to be used for the comparison of the efficacy of different types of closed needleless connectors against contamination. PMID- 26266925 TI - Effects of atrial natriuretic peptide on inter-organ crosstalk among the kidney, lung, and heart in a rat model of renal ischemia-reperfusion injury. AB - BACKGROUND: Renal ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury and a frequent occurrence in critically ill patients. Renal IRI releases proinflammatory cytokines within the kidney that induce crosstalk between the kidney and other organ systems. Atrial natriuretic peptide (ANP) has anti-inflammatory as well as natriuretic effects and serves important functions as a regulator of blood pressure, fluid homeostasis, and inflammation. The objective of the present study was to elucidate whether ANP post-treatment attenuates kidney-lung-heart crosstalk in a rat model of renal IRI. METHODS: In experiment I, a rat model of unilateral renal IRI with mechanical ventilation was prepared by clamping the left renal pedicle for 30 min. Five minutes after clamping, saline or ANP (0.2 MUg/kg/min) was infused. The hemodynamics, arterial blood gases, and plasma concentrations of lactate and potassium were measured at baseline and at 1, 2, and 3 h after declamping. The mRNA expression and localization of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL 6 in the kidney, lung, and heart were examined. In experiment II, a rat model of bilateral renal IRI without mechanical ventilation was prepared by clamping bilateral renal pedicles for 30 min. Thirty minutes after clamping, lactated Ringer's (LR) solution or ANP (0.2 MUg/kg/min) was infused. Plasma concentrations of TNF-alpha, IL-6, and IL-1beta were determined at baseline and at 3 h after declamping. RESULTS: In unilateral IRI rats with mechanical ventilation, ANP inhibited the following changes induced by IRI: metabolic acidosis; pulmonary edema; increases in lactate, creatinine, and potassium; and increases in the mRNA expression of TNF-alpha, IL-1beta, and IL-6 in the kidney and lung and IL-1beta and IL-6 in the heart. It also attenuated the histological localization of TNF alpha, IL-6, and nuclear factor (NF)-kappaB in the kidney and lung. In bilateral IRI rats without mechanical ventilation, ANP attenuated the IRI-induced increases of the plasma concentrations of potassium, IL-1beta, and IL-6. CONCLUSIONS: Renal IRI induced injury in remote organs including the lung and the contralateral kidney. ANP post-treatment ameliorated injuries in these organs by direct tissue protective effect and anti-inflammatory effects, which potentially inhibited inter-organ crosstalk. PMID- 26266926 TI - Macro- and micronutrient disposition in an ex vivo model of extracorporeal membrane oxygenation. AB - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) circuits have been shown to sequester circulating blood compounds such as drugs based on their physicochemical properties. This study aimed to describe the disposition of macro and micronutrients in simulated ECMO circuits. METHODS: Following baseline sampling, known quantities of macro- and micronutrients were injected post oxygenator into ex vivo ECMO circuits primed with the fresh human whole blood and maintained under standard physiologic conditions. Serial blood samples were then obtained at 1, 30 and 60 min and at 6, 12 and 24 h after the addition of nutrients, to measure the concentrations of study compounds using validated assays. RESULTS: Twenty-one samples were tested for thirty-one nutrient compounds. There were significant reductions (p < 0.05) in circuit concentrations of some amino acids [alanine (10%), arginine (95%), cysteine (14%), glutamine (25%) and isoleucine (7%)], vitamins [A (42%) and E (6%)] and glucose (42%) over 24 h. Significant increases in circuit concentrations (p < 0.05) were observed over time for many amino acids, zinc and vitamin C. There were no significant reductions in total proteins, triglycerides, total cholesterol, selenium, copper, manganese and vitamin D concentrations within the ECMO circuit over a 24-h period. No clear correlation could be established between physicochemical properties and circuit behaviour of tested nutrients. CONCLUSIONS: Significant alterations in macro- and micronutrient concentrations were observed in this single-dose ex vivo circuit study. Most significantly, there is potential for circuit loss of essential amino acid isoleucine and lipid soluble vitamins (A and E) in the ECMO circuit, and the mechanisms for this need further exploration. While the reductions in glucose concentrations and an increase in other macro- and micronutrient concentrations probably reflect cellular metabolism and breakdown, the decrement in arginine and glutamine concentrations may be attributed to their enzymatic conversion to ornithine and glutamate, respectively. While the results are generally reassuring from a macronutrient perspective, prospective studies in clinical subjects are indicated to further evaluate the influence of ECMO circuit on micronutrient concentrations and clinical outcomes. PMID- 26266927 TI - Early brain injury linearly correlates with reduction in cerebral perfusion pressure during the hyperacute phase of subarachnoid hemorrhage. AB - BACKGROUND: It is unclear how complex pathophysiological mechanisms that result in early brain injury (EBI) after subarachnoid hemorrhage (SAH) are triggered. We investigate how peak intracranial pressure (ICP), amount of subarachnoid blood, and hyperacute depletion of cerebral perfusion pressure (CPP) correlate to the onset of EBI following experimental SAH. METHODS: An entire spectrum of various degrees of SAH severities measured as peak ICP was generated and controlled using the blood shunt SAH model in rabbits. Standard cardiovascular monitoring, ICP, CPP, and bilateral regional cerebral blood flow (rCBF) were continuously measured. Cells with DNA damage and neurodegeneration were detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Fluoro jade B (FJB). RESULTS: rCBF was significantly correlated to reduction in CPP during the initial 15 min after SAH in a linear regression pattern (r (2) = 0.68, p < 0.001). FJB- and TUNEL-labeled cells were linearly correlated to reduction in CPP during the first 3 min of hemorrhage in the hippocampal regions (FJB: r (2) = 0.50, p < 0.01; TUNEL: r (2) = 0.35, p < 0.05), as well as in the basal cortex (TUNEL: r (2) = 0.58, p < 0.01). EBI occurred in animals with severe (relative CPP depletion >0.4) and moderate (relative CPP depletion >0.25 but <0.4) SAH. Neuronal cell death was equally detected in vulnerable and more resistant brain regions. CONCLUSIONS: The degree of EBI in terms of neuronal cell degeneration in both the hippocampal regions and the basal cortex linearly correlates with reduced CPP during hyperacute SAH. Temporary CPP reduction, however, is not solely responsible for EBI but potentially triggers processes that eventually result in early brain damage. PMID- 26266928 TI - Validation of computed tomography for measuring lung weight. AB - BACKGROUND: Lung weight characterises severity of pulmonary oedema and predicts response to mechanical ventilation. The aim of this study was to evaluate the accuracy of quantitative analysis of thorax computed tomography (CT) for measuring lung weight in pigs with or without pulmonary oedema. METHODS: Thirty six pigs were mechanically ventilated with different tidal volumes and positive end-expiratory pressures that did or did not induce pulmonary oedema. After 54 h, they underwent thorax CT (CT in vivo ) and were then sacrificed and exsanguinated. Fourteen pigs underwent a second thorax CT (CTpost-exsang.) after exsanguination. Lungs were excised and weighed with a balance (balancepost exsang.). Agreement between lung weights measured with the balance (considered as reference) and those estimated by quantitative analysis of CT was assessed with Bland-Altman plots. RESULTS: One animal unexpectedly died before CT in vivo . In 35 pigs, lung weight measured with balancepost-exsang. was 371 +/- 184 g and that estimated with CT in vivo was 481 +/- 189 g (p < 0.001). Bias between methods was -111 g (-35%) and limits of agreement were -176 (-63%) and -46 g (-8%). Measurement error was similar in animals with (-112 +/- 45 g; n = 11) or without (-110 +/- 27 g; n = 24) pulmonary oedema (p = 0.88). In 14 pigs with thorax CT after exsanguination, lung weight measured with balancepost-exsang. was 342 +/- 165 g and that estimated with CTpost-exsang. was 352 +/- 160 g (p = 0.02). Bias between methods was -9 g (-4%) and limits of agreement were -36 (-11%) and 17 g (3%). Measurement errors were similar in pigs with (-1 +/- 26 g; n = 11) or without (-12 +/- 7 g; n = 3) pulmonary oedema (p = 0.12). CONCLUSIONS: Compared to the balance, CT obtained in vivo constantly overestimated the lung weight, as it included pulmonary blood (whereas the balance did not). By contrast, CT obtained after exsanguination provided accurate and reproducible results. PMID- 26266929 TI - Systemic and renal hemodynamic effects of intra-arterial radiocontrast. AB - BACKGROUND: Decreased renal blood flow (RBF) and vasoconstriction are considered major mechanisms of contrast-induced acute kidney injury (CIAKI). To understand the severity and duration of such putative effects, we measured systemic and renal hemodynamics after intra-arterial radiocontrast administration. The subjects were six Merino ewes. The setting was a university-affiliated research institute. This is a randomized cross-over experimental study. METHODS: Transit time flow probes were implanted on the pulmonary and left renal arteries 2 weeks before experimentation. We simulated percutaneous coronary intervention by administering five intra-arterial boluses of 0.5 mL/kg saline (control) or radiocontrast (iodixanol) to a total of 2.5 mL/kg over 1 h. Cardiac output (CO), heart rate, mean arterial pressure (MAP), RBF, renal vascular conductance (RVC), urine output (UO), creatinine clearance (CrCl), and fractional excretion of sodium (FENa) were measured. RESULTS: In the first 8 h after intra-arterial administration of radiocontrast, CO, total peripheral conductance (TPC), and heart rate (HR) increased compared with those after normal saline administration. Thereafter, CO and TPC were similar between the two groups, but HR remained higher with radiocontrast (p < 0.001). After a short (30 min) period of renal vasoconstriction with preserved RBF secondary to an associated increase in MAP, RBF and RVC showed an earlier and greater increase (vasodilatation) with radiocontrast (p < 0.001) and remained higher during the first 2 days. Radiocontrast initially increased urine output (p < 0.001) and FENa (p = 0.003). However, the overall daily urine output decreased in the radiocontrast-treated animals at 2 days (p < 0.001) and 3 days (p = 0.006). Creatinine clearance was not affected. CONCLUSIONS: In healthy animals, intra-arterial radiocontrast increased RBF, induced renal vasodilatation, and caused a delayed period of oliguria. Our findings suggest that sustained reduction in RBF and renal vasoconstriction may not occur in normal large mammals after intra-arterial radiocontrast administration. PMID- 26266930 TI - Contrast-enhanced ultrasound evaluation of renal microcirculation in sheep. AB - BACKGROUND: Contrast-enhanced ultrasonography (CEUS) is a novel imaging modality to estimate microvascular perfusion. We aimed to assess renal cortical microcirculatory changes by CEUS during pharmacologically or mechanically induced modifications of renal blood flow (RBF) in experimental animals. METHODS: We implanted invasive transit-time Doppler flow probes and a vascular occluder around the renal artery in six Merino sheep. After induction of general anaesthesia, renal CEUS studies with destruction-replenishment sequences were performed at baseline and after different interventions aimed at modifying RBF. First, we administered angiotensin II (AngII) to achieve a 25% (AngII 25%) and 50% (AngII 50%) decrease in RBF. Then, we applied mechanical occlusion of the renal artery until RBF decreased by 25% (Occl 25%) and 50% (Occl 50%) of the baseline. Finally, a single dose of 25 mg of captopril was administered. CEUS sequences were analysed offline with dedicated software and perfusion indices (PI) calculated. RESULTS: Pharmacological reduction of RBF with AngII was associated with a 62% (range: 68 decrease to 167 increase) increase (AngII 25%) and a 5% increase in PI (range: 92% decrease to 53% increase) (AngII 50%) in PI. Mechanical occlusion of the renal artery was associated with a 2% (range: 43% decrease to 2% increase) decrease (Occl 25%) and a 67% (range: 63% decrease to a 120% increase) increase (Occl 50%) in PI. The administration of captopril was associated with a 8% (range: 25% decrease to a 101% increase) decrease in PI. Pooled changes in PI failed to reach statistical significance. The study was limited by the difficulty to obtain high quality images. CONCLUSIONS: CEUS derived parameters were highly heterogeneous in this sheep model. The current protocol and model did not allow the evaluation of the correlation between macro and microcirculation assessment by CEUS. PMID- 26266931 TI - Sepsis-induced acute kidney injury by standardized colon ascendens stent peritonitis in rats - a simple, reproducible animal model. AB - BACKGROUND: Up to 50% of septic patients develop acute kidney injury (AKI). The pathomechanism of septic AKI is poorly understood. Therefore, we established an innovative rodent model to characterize sepsis-induced AKI by standardized colon ascendens stent peritonitis (sCASP). The model has a standardized focus of infection, an intensive care set up with monitoring of haemodynamics and oxygenation resulting in predictable impairment of renal function, AKI parameters as well as histopathology scoring. METHODS: Anaesthetized rats underwent the sCASP procedure, whereas sham animals were sham operated and control animals were just monitored invasively. Haemodynamic variables and blood gases were continuously measured. After 24 h, animals were reanesthetized; cardiac output (CO), inulin and PAH clearances were measured and later on kidneys were harvested; and creatinine, urea, cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) were analysed. Additional sCASP-treated animals were investigated after 3 and 9 days. RESULTS: All sCASP-treated animals survived, whilst ubiquitous peritonitis and significantly deteriorated clinical and macrohaemodynamic sepsis signs after 24 h (MAP, CO, heart rate) were obvious. Blood analyses showed increased lactate and IL-6 levels as well as leucopenia. Urine output, inulin and PAH clearance were significantly decreased in sCASP compared to sham and control. Additionally, significant increase in cystatin C and NGAL was detected. Standard parameters like serum creatinine and urea were elevated and sCASP-induced sepsis increased significantly in a time-dependent manner. The renal histopathological score of sCASP-treated animals deteriorated after 3 and 9 days. CONCLUSIONS: The presented sCASP method is a standardized, reliable and reproducible method to induce septic AKI. The intensive care set up, continuous macrohaemodynamic and gas exchange monitoring, low mortality rate as well as the opportunity of detailed analyses of kidney function and impairments are advantages of this setup. Thus, our described method may serve as a new standard for experimental investigations of septic AKI. PMID- 26266932 TI - Rice bran prevents high-fat diet-induced inflammation and macrophage content in adipose tissue. AB - BACKGROUND: The inflammatory process associated with obesity mainly arises from white adipose tissue (WAT) alterations. In the last few years, nutritional-based strategies have been positioned as promising alternatives to pharmacological approaches against these pathologies. Our aim was to determine the potential of a rice bran enzymatic extract (RBEE)-supplemented diet in the prevention of metabolic, biochemical and functional adipose tissue and macrophage changes associated with a diet-induced obesity (DIO) in mice. METHODS: C57BL/6J mice were fed high-fat diet (HF), 1 and 5 % RBEE-supplemented high-fat diet (HF1 % and HF5 %, respectively) and standard diet as control. Serum cardiometabolic parameters, adipocytes size and mRNA expression of pro-inflammatory biomarkers and macrophage polarization-related genes from WAT and liver were evaluated. RESULTS: RBEE administration significantly decreased insulin resistance in obese mice. Serum triglycerides, total cholesterol, glucose, insulin, adiponectin and nitrites from treated mice were partially restored, mainly by 1 % RBEE-enriched diet. The incremented adipocytes size observed in HF group was reduced by RBEE treatment, being 1 % more effective than 5 % RBEE. Pro-inflammatory biomarkers in WAT such as IL-6 and IL-1beta were significantly decreased in RBEE-treated mice. Adiponectin, PPARgamma, TNF-alpha, Emr1 or M1/M2 levels were significantly restored in WAT from HF1 % compared to HF mice. CONCLUSIONS: RBEE-supplemented diet attenuated insulin resistance, dyslipidemia and morphological and functional alterations of adipose tissue in DIO mice. These benefits were accompanied by a modulating effect in adipocytes secretion and some biomarkers associated with macrophage polarization. Therefore, RBEE may be considered an alternative nutritional complement over metabolic syndrome and its complications. PMID- 26266933 TI - FAH domain containing protein 1 (FAHD-1) is required for mitochondrial function and locomotion activity in C. elegans. AB - The fumarylacetoacetate hydrolase (FAH) protein superfamily of metabolic enzymes comprises a diverse set of enzymatic functions, including beta-diketone hydrolases, decarboxylases, and isomerases. Of note, the FAH superfamily includes many prokaryotic members with very distinct functions that lack homologs in eukaryotes. A prokaryotic member of the FAH superfamily, referred to as Cg1458, was shown to encode a soluble oxaloacetate decarboxylase (ODx). Based on sequence homologies to Cg1458, we recently identified human FAH domain containing protein 1 (FAHD1) as the first eukaryotic oxaloacetate decarboxylase. The physiological functions of ODx in eukaryotes remain unclear. Here we have probed the function of fahd-1, the nematode homolog of FAHD1, in the context of an intact organism. We found that mutation of fahd-1 resulted in reduced brood size, a deregulation of the egg laying process and a severe locomotion deficit, characterized by a reduced frequency of body bends, reduced exploratory movements and reduced performance in an endurance exercise test. Notably, mitochondrial function was altered in the fahd-1(tm5005) mutant strain, as shown by a reduction of mitochondrial membrane potential and a reduced oxygen consumption of fahd 1(tm5005) animals. Mitochondrial dysfunction was accompanied by lifespan extension in worms grown at elevated temperature; however, unlike in mutant worms with a defect in the electron transport chain, the mitochondrial unfolded protein response was not upregulated in worms upon inactivation of fahd-1. Together these data establish a role of fahd-1 to maintain mitochondrial function and consequently physical activity in nematodes. PMID- 26266934 TI - Microevolution of Anthrax from a Young Ancestor (M.A.Y.A.) Suggests a Soil-Borne Life Cycle of Bacillus anthracis. AB - During an anthrax outbreak at the Pollino National Park (Basilicata, Italy) in 2004, diseased cattle were buried and from these anthrax-foci Bacillus anthracis endospores still diffuse to the surface resulting in local accumulations. Recent data suggest that B. anthracis multiplies in soil outside the animal-host body. This notion is supported by the frequent isolation of B. anthracis from soil lacking one or both virulence plasmids. Such strains represent an evolutionary dead end, as they are likely no longer able to successfully infect new hosts. This loss of virulence plasmids is explained most simply by postulating a soil borne life cycle of the pathogen. To test this hypothesis we investigated possible microevolution at two natural anthrax foci from the 2004 outbreak. If valid, then genotypes of strains isolated from near the surface at these foci should be on a different evolutionary trajectory from those below residing in deeper-laying horizons close to the carcass. Thus, the genetic diversity of B. anthracis isolates was compared conducting Progressive Hierarchical Resolving Assays using Nucleic Acids (PHRANA) and next generation Whole Genome Sequencing (WGS). PHRANA was not discriminatory enough to resolve the fine genetic relationships between the isolates. Conversely, WGS of nine isolates from near surface and nine from near-carcass revealed five isolate specific SNPs, four of which were found only in different near-surface isolates. In support of our hypothesis, one surface-isolate lacked plasmid pXO1 and also harbored one of the unique SNPs. Taken together, our results suggest a limited soil-borne life cycle of B. anthracis. PMID- 26266935 TI - Child Allergic Symptoms and Well-Being at School: Findings from ALSPAC, a UK Cohort Study. AB - BACKGROUND: Eczema and asthma are common conditions in childhood that can influence children's mental health. Despite this, little is known about how these conditions affect the well-being of children in school. This study examines whether symptoms of eczema or asthma are associated with poorer social and mental well-being in school as reported by children and their teachers at age 8 years. METHODS: Participants were from the Avon Longitudinal Study of Parents and Children. Measures of child well-being in school were child-reported (n = 6626) and teacher reported (n = 4366): children reported on their enjoyment of school and relationships with peers via a self-complete questionnaire; teachers reported child mental well-being using the Strengths and Difficulties Questionnaire [binary outcomes were high 'internalizing' (anxious/depressive) and 'externalizing' (oppositional/hyperactive) problems (high was >90th percentile)]. Child rash and wheeze status were maternally reported and symptoms categorised as: 'none'; 'early onset transient' (infancy/preschool only); 'persistent' (infancy/preschool and at school age); and 'late onset' (school age only). RESULTS: Children with persistent (OR 1.29, 95% CI 1.02 to 1.63) and late onset (OR 1.48, 95% CI 1.02 to 2.14) rash were more likely to report being bullied, and children with persistent wheeze to feel left out (OR 1.42, 95% CI 1.10 to 1.84). Late onset rash was associated with high teacher-reported internalising behaviours (OR 1.61, 95% CI 1.02 to 2.54), and persistent rash with high externalising behaviours (OR 1.37, 95% CI 1.02 to 1.84). Child sleep and maternal mental health explained some of the associations with teacher-reported mental well-being. CONCLUSION: Symptoms of eczema or asthma can adversely affect a child's social and mental well-being at primary school. This suggests interventions, such as additional support or education of peers, should begin at early stages in schooling. PMID- 26266936 TI - In vitro glycoengineering of IgG1 and its effect on Fc receptor binding and ADCC activity. AB - The importance and effect of Fc glycosylation of monoclonal antibodies with regard to biological activity is widely discussed and has been investigated in numerous studies. Fc glycosylation of monoclonal antibodies from current production systems is subject to batch-to-batch variability. If there are glycosylation changes between different batches, these changes are observed not only for one but multiple glycan species. Therefore, studying the effect of distinct Fc glycan species such as galactosylated and sialylated structures is challenging due to the lack of well-defined differences in glycan patterns of samples used. In this study, the influence of IgG1 Fc galactosylation and sialylation on its effector functions has been investigated using five different samples which were produced from one single drug substance batch by in vitro glycoengineering. This sample set comprises preparations with minimal and maximal galactosylation and different levels of sialylation of fully galactosylated Fc glycans. Among others, Roche developed the glycosyltransferase enzyme sialyltransferase which was used for the in vitro glycoengineering activities at medium scale. A variety of analytical assays, including Surface Plasmon Resonance and recently developed FcgammaR affinity chromatography, as well as an optimized cell-based ADCC assay were applied to investigate the effect of Fc galactosylation and sialylation on the in vitro FcgammaRI, IIa, and IIIa receptor binding and ADCC activity of IgG1. The results of our studies do not show an impact, neither positive nor negative, of sialic acid- containing Fc glycans of IgG1 on ADCC activity, FcgammaRI, and RIIIa receptors, but a slightly improved binding to FcgammaRIIa. Furthermore, we demonstrate a galactosylation-induced positive impact on the binding activity of the IgG1 to FcgammaRIIa and FcgammaRIIIa receptors and ADCC activity. PMID- 26266937 TI - New Caledonian crows rapidly solve a collaborative problem without cooperative cognition. AB - There is growing comparative evidence that the cognitive bases of cooperation are not unique to humans. However, the selective pressures that lead to the evolution of these mechanisms remain unclear. Here we show that while tool-making New Caledonian crows can produce collaborative behavior, they do not understand the causality of cooperation nor show sensitivity to inequity. Instead, the collaborative behavior produced appears to have been underpinned by the transfer of prior experience. These results suggest that a number of possible selective pressures, including tool manufacture and mobbing behaviours, have not led to the evolution of cooperative cognition in this species. They show that causal cognition can evolve in a domain specific manner-understanding the properties and flexible uses of physical tools does not necessarily enable animals to grasp that a conspecific can be used as a social tool. PMID- 26266938 TI - Kharon1 null mutants of Leishmania mexicana are avirulent in mice and exhibit a cytokinesis defect within macrophages. AB - In a variety of eukaryotes, flagella play important roles both in motility and as sensory organelles that monitor the extracellular environment. In the parasitic protozoan Leishmania mexicana, one glucose transporter isoform, LmxGT1, is targeted selectively to the flagellar membrane where it appears to play a role in glucose sensing. Trafficking of LmxGT1 to the flagellar membrane is dependent upon interaction with the KHARON1 protein that is located at the base of the flagellar axoneme. Remarkably, while Deltakharon1 null mutants are viable as insect stage promastigotes, they are unable to survive as amastigotes inside host macrophages. Although Deltakharon1 promastigotes enter macrophages and transform into amastigotes, these intracellular parasites are unable to execute cytokinesis and form multinucleate cells before dying. Notably, extracellular axenic amastigotes of Deltakharon1 mutants replicate and divide normally, indicating a defect in the mutants that is only exhibited in the intra-macrophage environment. Although the flagella of Deltakharon1 amastigotes adhere to the phagolysomal membrane of host macrophages, the morphology of the mutant flagella is often distorted. Additionally, these null mutants are completely avirulent following injection into BALB/c mice, underscoring the critical role of the KHARON1 protein for viability of intracellular amastigotes and disease in the animal model of leishmaniasis. PMID- 26266939 TI - Following the trail: factors underlying the sudden expansion of the Egyptian mongoose (Herpestes ichneumon) in Portugal. AB - Species range-limits are influenced by a combination of several factors. In our study we aimed to unveil the drivers underlying the expansion of the Egyptian mongoose in Portugal, a carnivore that was confined to southern Portugal and largely increased its range during the last three decades. We evaluated the expansion of the species in three periods (1980-1990, 1990-2000 and 2000-2010), by projecting the presence/absence data of the species in each temporal range and proposed four hypotheses to explain this sudden expansion associated to changes in the barrier effects of human infrastructure and topographic features, and in the availability of suitable areas due to climate change or land use. An exploratory analysis was made using Spearman rank correlation, followed by a hierarchical partitioning analysis to select uncorrelated potential explanatory variables associated with the different hypotheses. We then ran Generalized Linear Models (GLM) for every period for each hypothesis and for every combination of hypotheses. Our main findings suggest that dynamic transitions of land-use coupled with temperature and rainfall variations over the decades are the main drivers promoting the mongoose expansion. The geographic barriers and the human infrastructures functioned as barriers for mongoose expansion and have shaped its distribution. The expansion of the Egyptian mongoose across the Portuguese territory was due to a variety of factors. Our results suggest a rapid shift in species range in response to land-use and climate changes, underlining the close link between species ranges and a changing environment. PMID- 26266940 TI - A reddish nodule with viscous fluid secretion. Solid-cystic hidradenoma (SCH). PMID- 26266942 TI - Silver-coated endotracheal tubes for prevention of ventilator-associated pneumonia in critically ill patients. AB - BACKGROUND: Ventilator-associated pneumonia (VAP) is one of the most common nosocomial infections in intubated and mechanically ventilated patients. Endotracheal tubes (ETTs) appear to be an independent risk factor for VAP. Silver coated ETTs slowly release silver cations. It is these silver ions that appear to have a strong antimicrobial effect. Because of this antimicrobial effect of silver, silver-coated ETTs could be an effective intervention to prevent VAP in people who require mechanical ventilation for 24 hours or longer. OBJECTIVES: Our primary objective was to investigate whether silver-coated ETTs are effective in reducing the risk of VAP and hospital mortality in comparison with standard non coated ETTs in people who require mechanical ventilation for 24 hours or longer. Our secondary objective was to ascertain whether silver-coated ETTs are effective in reducing the following clinical outcomes: device-related adverse events, duration of intubation, length of hospital and intensive care unit (ICU) stay, costs, and time to VAP onset. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014 Issue 10, MEDLINE, EMBASE, EBSCO CINAHL, and reference lists of trials. We contacted corresponding authors for additional information and unpublished studies. We did not impose any restrictions on the basis of date of publication or language. The date of the last search was October 2014. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) and quasi-randomized trials that evaluated the effects of silver-coated ETTs or a combination of silver with any antimicrobial-coated ETTs with standard non-coated ETTs or with other antimicrobial-coated ETTs in critically ill people who required mechanical ventilation for 24 hours or longer. We also included studies that evaluated the cost-effectiveness of silver-coated ETTs or a combination of silver with any antimicrobial-coated ETTs. DATA COLLECTION AND ANALYSIS: Two review authors (GT, HV) independently extracted the data and summarized study details from all included studies using the specially designed data extraction form. We used standard methodological procedures expected by The Cochrane Collaboration. We performed meta-analysis for outcomes when possible. MAIN RESULTS: We found three eligible randomized controlled trials, with a total of 2081 participants. One of the three included studies did not mention the amount of participants and presented no outcome data. The 'Risk of bias' assessment indicated that there was a high risk of detection bias owing to lack of blinding of outcomes assessors, but we assessed all other domains to be at low risk of bias. Trial design and conduct were generally adequate, with the most common areas of weakness in blinding. The majority of participants were included in centres across North America. The mean age of participants ranged from 61 to 64 years, and the mean duration of intubation was between 3.2 and 7.7 days. One trial comparing silver-coated ETTs versus non-coated ETTs showed a statistically significant decrease in VAP in favour of the silver-coated ETT (1 RCT, 1509 participants; 4.8% versus 7.5%, risk ratio (RR) 0.64, 95% confidence interval (CI) 0.43 to 0.96; number needed to treat for an additional beneficial outcome (NNTB) = 37; low-quality evidence). The risk of VAP within 10 days of intubation was significantly lower with the silver-coated ETTs compared with non coated ETTs (1 RCT, 1509 participants; 3.5% versus 6.7%, RR 0.51, 95% CI 0.31 to 0.82; NNTB = 32; low-quality evidence). Silver-coated ETT was associated with delayed time to VAP occurrence compared with non-coated ETT (1 RCT, 1509 participants; hazard ratio 0.55, 95% CI 0.37 to 0.84). The confidence intervals for the results of the following outcomes did not exclude potentially important differences with either treatment. There were no statistically significant differences between groups in hospital mortality (1 RCT, 1509 participants; 30.4% versus 26.6%, RR 1.09, 95% CI 0.93 to 1.29; low-quality evidence); device-related adverse events (2 RCTs, 2081 participants; RR 0.65, 95% CI 0.37 to 1.16; low quality evidence); duration of intubation; and length of hospital and ICU stay. We found no clinical studies evaluating the cost-effectiveness of silver-coated ETTs. AUTHORS' CONCLUSIONS: This review provides limited evidence that silver coated ETT reduces the risk of VAP, especially during the first 10 days of mechanical ventilation. PMID- 26266941 TI - Comprehensive Assessment of Host Responses to 5-Fluorouracil-Induced Oral Mucositis through Transcriptomic Analysis. AB - BACKGROUND: Chemotherapy plays an important role in current cancer therapy; however, several problems remain unsolved on the issue of host-therapeutics interaction. The purpose of this study was to investigate the host responses after 5-flurouracil (5-FU) administration and to find the target genes and their relationship with other cytokines in the 5-FU-induced oral mucositis (OM) mouse model through transcriptomic analysis. MATERIALS AND METHODS: Thirty-six 6 to 8 week-old male BALB/c mice were randomly divided into the control group and 5-FU treated group. In the 5-FU group, mice received 5-FU (100 mg/kg, intraperitoneally) on day 1, day 8, day 15, day 22, and day 29, respectively. We evaluated the oral mucosal change under macroanalysis and histological examination at indicated periods, and then applied transcriptomic analysis of gene expression profile and Immunohistochemical stain to identify the target molecules related to 5-FU-induced OM. RESULTS: The most prominent histological change in this model was observed in the fifth week. The gene expression of Bone gamma-carboxyglutamate protein, related sequence 1 (Bglap-rs1) (-12.69-fold) and Chitinase 3-like 4 (Chi3l4) (-6.35-fold) were significantly down-regulated in this phase. The quantitative real-time PCR results also revealed the expression levels were 0.62-fold in Bglap-rs1 and 0.13-fold in Chi3l4 compared with the control group. Immunohistochemical stain showed significant expression of cluster of differentiation 11b (p<0.01), interleukin-1beta (p<0.001) and tumor necrosis factor-alpha (p<0.05), and down-regulation of Bglap-rs1 (p<0.01) compared with the control group. By Kyoto Encyclopedia of Genes and Genomes pathway analysis, there were twenty-three pathways significantly participated in this study (p<0.05). CONCLUSIONS: Through comprehensively transcriptomic analysis and IHC stain, we discovered several valuable pathways, verified the main pro inflammatory cytokines, and revealed two significantly down-regulated genes in the 5-FU-induced OM model. These findings highlighted the way of seeking effective therapeutic agents for chemotherapy-induced OM in future. PMID- 26266943 TI - Induction of Neural Progenitor-Like Cells from Human Fibroblasts via a Genetic Material-Free Approach. AB - BACKGROUND: A number of studies generated induced neural progenitor cells (iNPCs) from human fibroblasts by viral delivering defined transcription factors. However, the potential risks associated with gene delivery systems have limited their clinical use. We propose it would be safer to induce neural progenitor-like cells from human adult fibroblasts via a direct non-genetic alternative approach. METHODOLOGY/PRINCIPAL FINDINGS: Here, we have reported that seven rounds of TAT SOX2 protein transduction in a defined chemical cocktail under a 3D sphere culture gradually morphed fibroblasts into neuroepithelial-like colonies. We were able to expand these cells for up to 20 passages. These cells could give rise to cells that expressed neurons and glia cell markers both in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE: These results show that our approach is beneficial for the genetic material-free generation of iNPCs from human fibroblasts where small chemical molecules can provide a valuable, viable strategy to boost and improve induction in a 3D sphere culture. PMID- 26266944 TI - HCV Infection and Interferon-Based Treatment Induce p53 Gene Transcription in Chronic Hepatitis C Patients. AB - It is suggested that the tumor suppressor p53 gene, classified as an interferon stimulated gene, is implicated in the interferon (IFN)-mediated innate immunity against viruses. This study aimed to examine the transcriptional response of the p53 gene to hepatitis C virus (HCV) infection and IFN-based therapy in chronic hepatitis C (CHC) patients. The study included 65 CHC patients (HCV genotype 1), treated with pegylated IFN-alpha and ribavirin, and 51 healthy individuals. p53 gene expression was quantified by real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMCs). Analyses were performed before and at weeks 4 and 12 of treatment. p53 gene expression was significantly upregulated in CHC patients compared with healthy controls and at week 4 of therapy. No significant differences in p53 mRNA expression between rapid virologic responders, complete early virologic responders, and nonresponders were observed. No significant correlation was found between p53 gene expression and viral load. The results obtained indicate that HCV infection and IFN-based treatment induces p53 gene transcription in PBMCs. The p53 gene may therefore play a role in HCV infection but is not directly involved in treatment-induced HCV elimination. Moreover, variations in p53 gene expression do not determine on-treatment response in patients with chronic HCV genotype 1 infection. PMID- 26266945 TI - A Hamster Model of Diet-Induced Obesity for Preclinical Evaluation of Anti Obesity, Anti-Diabetic and Lipid Modulating Agents. AB - AIM: Unlike rats and mice, hamsters develop hypercholesterolemia, and hypertriglyceridemia when fed a cholesterol-rich diet. Because hyperlipidemia is a hallmark of human obesity, we aimed to develop and characterize a novel diet induced obesity (DIO) and hypercholesterolemia Golden Syrian hamster model. METHODS AND RESULTS: Hamsters fed a highly palatable fat- and sugar-rich diet (HPFS) for 12 weeks showed significant body weight gain, body fat accumulation and impaired glucose tolerance. Cholesterol supplementation to the diet evoked additional hypercholesterolemia. Chronic treatment with the GLP-1 analogue, liraglutide (0.2 mg/kg, SC, BID, 27 days), normalized body weight and glucose tolerance, and lowered blood lipids in the DIO-hamster. The dipeptidyl peptidase 4 (DPP-4) inhibitor, linagliptin (3.0 mg/kg, PO, QD) also improved glucose tolerance. Treatment with peptide YY3-36 (PYY3-36, 1.0 mg/kg/day) or neuromedin U (NMU, 1.5 mg/kg/day), continuously infused via a subcutaneous osmotic minipump for 14 days, reduced body weight and energy intake and changed food preference from HPFS diet towards chow. Co-treatment with liraglutide and PYY3-36 evoked a pronounced synergistic decrease in body weight and food intake with no lower plateau established. Treatment with the cholesterol uptake inhibitor ezetimibe (10 mg/kg, PO, QD) for 14 days lowered plasma total cholesterol with a more marked reduction of LDL levels, as compared to HDL, indicating additional sensitivity to cholesterol modulating drugs in the hyperlipidemic DIO-hamster. In conclusion, the features of combined obesity, impaired glucose tolerance and hypercholesterolemia in the DIO-hamster make this animal model useful for preclinical evaluation of novel anti-obesity, anti-diabetic and lipid modulating agents. PMID- 26266946 TI - Mobilizing Community Resources to Enhance Postdischarge Support for Breastfeeding in Massachusetts (USA): Results of a Catalyst Grant Approach. AB - BACKGROUND: The Massachusetts Department of Public Health's (MDPH) Mass in Motion Program (MiM) facilitates the adoption of community-level strategies that promote healthy weight in 52 municipalities. MiM provided the platform for enhancing postdischarge continuity of care for breastfeeding. OBJECTIVE: This study aimed to improve the continuity of breastfeeding care and support for mothers by enhancing postdischarge care infrastructure and supportive contacts for women and families. METHODS: The MDPH awarded catalyst grants to community-based organizations (CBOs) that facilitated the formation of teams for improving breastfeeding support. The effort focused on populations that often experience disparities in breastfeeding outcomes such as minority women and women receiving Medicaid. The Added Value Model of Community Coalitions was used to qualitatively assess effect across multiple levels of the socioecological model of influence. RESULTS: Six communities were awarded grants to enhance or convene Breastfeeding Continuity-of-Care Teams consisting of at least 3 CBOs, including 1 maternity hospital, the local Special Supplemental Nutrition Program for Women, Infants, and Children, and the local MiM representative. Teams implemented customized plans with performance indicators to create and strengthen infrastructure for supportive contacts with breastfeeding mothers. The project included Baby Cafe pilots in 3 additional MiM communities. Across all grantee communities, there was an average total increase of 491 contacts with mothers per month, an improvement of 8.5% over baseline. The project created 153 added value outcomes of community collaboration at 5 levels in the socioecological framework. CONCLUSION: The project demonstrated how cross-sector, coordinated efforts focused on vulnerable populations can leverage local strengths to establish/enhance breastfeeding support services customized to local needs. PMID- 26266947 TI - Breastfeeding Resources in Maternity Hospitals and Birth Centers in the Commonwealth of Massachusetts (USA): A Content Analysis of Discharge Packets. AB - BACKGROUND: Few studies have analyzed patient education materials provided at discharge. To the best of our knowledge, there are no comprehensive studies analyzing and reporting the content of breastfeeding discharge packets within the United States. OBJECTIVE: This study analyzed the extent to which patient education materials provided at discharge from maternity facilities in Massachusetts cover topics that support successful breastfeeding. METHODS: We collected discharge packets from all 48 maternity hospitals/birth centers. Topics for analysis were based on recommendations associated with the Baby-Friendly Hospital Initiative and content identified for discharge packets generally. Materials were reviewed independently and scored according to 39 criteria that we assembled from various sources for optimal breastfeeding information at discharge. Bivariate and multivariate analyses were used to explore if any hospital characteristics predicted presence of breastfeeding education topics in written information provided at discharge. RESULTS: An average of 25.4 of 39 criteria (65.2%, ranging from 30.7%-97.4%) were included in packets submitted by all 48 facilities. Exploratory multivariate analyses did not show relationships of hospital characteristics to contents of packets. Each facility received a 2 page report noting strengths, suggestions for improvement, and individual scores on all 39 criteria. CONCLUSION: Discharge packet contents varied widely; whereas some institutions' information met and/or exceeded recommended content, others were limited and/or missing information. These analyses provide a thorough review of discharge packet content for all facilities in Massachusetts; however, further study is needed to identify the implications of such variation for breastfeeding outcomes. PMID- 26266948 TI - Bcl-2 is required for the survival of doublecortin-expressing immature neurons. AB - In the adult brain only a small proportion of the neural stem and progenitor cells (NPCs) and their progeny survive to become mature neurons in the hippocampus. Recent studies have elucidated the roles for members of the B-cell lymphoma-2 (Bcl-2) family of proteins in regulating the survival of NPCs and their progeny at different stages of maturation, yet the requirement of Bcl-2 during this process remains unknown. Here we report that inducible removal of Bcl 2 from nestin-expressing neural stem/progenitor cells and their progeny resulted in a reduction in the survival of doublecortin-expressing cells in the absence of changing the number of radial-glial stem cells or dividing NPCs. The requirement of Bcl-2 for the survival of maturing NPCs was confirmed by removal of Bcl-2 through infecting NPCs using a retroviral strategy that resulted in the complete loss of Bcl-2 null cells by 30-day post-viral injection. Furthermore, we observed that the function of Bcl-2 in the adult-generated neurons was dependent on the Bcl-2-associated X (BAX) protein, since Bcl-2 null NPCs were rescued in BAX knockout mice. These results indicate that Bcl-2 is an essential regulator in the survival of doublecortin-expressing immature neurons through a mechanism that is upstream of BAX. PMID- 26266949 TI - Knowledge on HPV Vaccine and Cervical Cancer Facilitates Vaccine Acceptability among School Teachers in Kitui County, Kenya. AB - BACKGROUND: Vaccines against human papillomavirus (HPV) infection have the potential to reduce the burden of cervical cancer. School-based delivery of HPV vaccines is cost-effective and successful uptake depends on school teachers' knowledge and acceptability of the vaccine. The aim of this study is to assess primary school teachers' knowledge and acceptability of HPV vaccine and to explore facilitators and barriers of an ongoing Gavi Alliance-supported vaccination program in Kitui County, Kenya. METHODS: This was a cross-sectional, mixed methods study in Central Division of Kitui County where the Ministry of Health is offering the quadrivalent HPV vaccine to grade four girls. Data on primary school teachers' awareness, knowledge and acceptability of HPV vaccine as well as facilitators and barriers to the project was collected through self administered questionnaires and two focus group discussions. RESULTS: 339 teachers (60% female) completed the survey (62% response rate) and 13 participated in 2 focus group discussions. Vaccine awareness among teachers was high (90%), the level of knowledge about HPV and cervical cancer among teachers was moderate (48%, SD = 10.9) and females scored higher than males (50% vs. 46%, p = 0.002). Most teachers (89%) would recommend the vaccine to their daughter or close relatives. Those who would recommend the vaccine had more knowledge than those who would not (p = <0.001). The main barriers were insufficient information about the vaccine, poor accessibility of schools, absenteeism of girls on vaccine days, and fear of side effects. CONCLUSIONS: Despite low to moderate levels of knowledge about HPV vaccine among school teachers, vaccine acceptability is high. Teachers with little knowledge on HPV vaccine are less likely to accept the vaccine than those who know more; this may affect uptake if not addressed. Empowering teachers to be vaccine champions in their community may be a feasible way of disseminating information about HPV vaccine and cervical cancer. PMID- 26266950 TI - Gastric inhibitory polypeptide (GIP) is selectively decreased in the roux-limb of dietary obese mice after RYGB surgery. AB - Gastric inhibitory polypeptide (GIP, glucose-dependent insulinotropic polypeptide) is expressed by intestinal K cells to regulate glucose-induced insulin secretion. The impact of Roux-en Y bypass (RYGB) surgery on blood GIP is highly contraversial. This study was conducted to address the mechanism of controversy. GIP mRNA was examined in the intestine, and serum GIP was determined using Luminex and ELISA in diet-induced obese (DIO) mice. The assays were conducted in RYGB mice in fasting and fed conditions. Food preference, weight loss and insulin sensitivity were monitored in RYGB mice. In DIO mice, GIP mRNA was increased by 80% in all sections of the small intestine over the lean control. The increase was observed in both fasting and fed conditions. After RYGB surgery, the food-induced GIP expression was selectively reduced in the Roux limb, but not in the biliopancreatic and common limbs of intestine in fed condition. Lack of stimulation by glucose or cholesterol contributed to the reduction. Jejunal mucosa of Roux-limb exhibited hypertrophy, but villous surface was decreased by the undigested food. Serum GIP (total) was significantly higher in the fasting condition, but not in the fed condition due to attenuated GIP response to food intake in RYGB mice. The GIP alteration was associated with chow diet preference, sustained weight loss and insulin sensitization in RYGB mice. RYGB increased serum GIP in the fasting, but not in the fed conditions. The loss of food-induced GIP response in Roux-limb of intestine likely contributes to the attenuated serum GIP response to feeding. PMID- 26266951 TI - Definition of Eight Mulberry Species in the Genus Morus by Internal Transcribed Spacer-Based Phylogeny. AB - Mulberry, belonging to the order Rosales, family Moraceae, and genus Morus, has received attention because of both its economic and medicinal value, as well as for its important ecological function. The genus Morus has a worldwide distribution, however, its taxonomy remains complex and disputed. Many studies have attempted to classify Morus species, resulting in varied numbers of designated Morus spp. To address this issue, we used information from internal transcribed spacer (ITS) genetic sequences to study the taxonomy of all the members of generally accepted genus Morus. We found that intraspecific 5.8S rRNA sequences were identical but that interspecific 5.8S sequences were diverse. M. alba and M. notabilis showed the shortest (215 bp) and the longest (233 bp) ITS1 sequence length, respectively. With the completion of the mulberry genome, we could identify single nucleotide polymorphisms within the ITS locus in the M. notabilis genome. From reconstruction of a phylogenetic tree based on the complete ITS data, we propose that the Morus genus should be classified into eight species, including M. alba, M. nigra, M. notabilis, M. serrata, M. celtidifolia, M. insignis, M. rubra, and M. mesozygia. Furthermore, the classification of the ITS sequences of known interspecific hybrid clones into both paternal and maternal clades indicated that ITS variation was sufficient to distinguish interspecific hybrids in the genus Morus. PMID- 26266952 TI - Correction: A New Method for Estimating the Number of Undiagnosed HIV Infected Based on HIV Testing History, with an Application to Men Who Have Sex with Men in Seattle/King County, WA. PMID- 26266953 TI - The Beta Cell in Its Cluster: Stochastic Graphs of Beta Cell Connectivity in the Islets of Langerhans. AB - Pancreatic islets of Langerhans consist of endocrine cells, primarily alpha, beta and delta cells, which secrete glucagon, insulin, and somatostatin, respectively, to regulate plasma glucose. beta cells form irregular locally connected clusters within islets that act in concert to secrete insulin upon glucose stimulation. Due to the central functional significance of this local connectivity in the placement of beta cells in an islet, it is important to characterize it quantitatively. However, quantification of the seemingly stochastic cytoarchitecture of beta cells in an islet requires mathematical methods that can capture topological connectivity in the entire beta-cell population in an islet. Graph theory provides such a framework. Using large-scale imaging data for thousands of islets containing hundreds of thousands of cells in human organ donor pancreata, we show that quantitative graph characteristics differ between control and type 2 diabetic islets. Further insight into the processes that shape and maintain this architecture is obtained by formulating a stochastic theory of beta-cell rearrangement in whole islets, just as the normal equilibrium distribution of the Ornstein-Uhlenbeck process can be viewed as the result of the interplay between a random walk and a linear restoring force. Requiring that rearrangements maintain the observed quantitative topological graph characteristics strongly constrained possible processes. Our results suggest that beta-cell rearrangement is dependent on its connectivity in order to maintain an optimal cluster size in both normal and T2D islets. PMID- 26266955 TI - Recurrent pustules on an infant's scalp with neonatal onset. PMID- 26266954 TI - Optimizing stimulation and analysis protocols for neonatal fMRI. AB - The development of brain function in young infants is poorly understood. The core challenge is that infants have a limited behavioral repertoire through which brain function can be expressed. Neuroimaging with fMRI has great potential as a way of characterizing typical development, and detecting abnormal development early. But, a number of methodological challenges must first be tackled to improve the robustness and sensitivity of neonatal fMRI. A critical one of these, addressed here, is that the hemodynamic response function (HRF) in pre-term and term neonates differs from that in adults, which has a number of implications for fMRI. We created a realistic model of noise in fMRI data, using resting-state fMRI data from infants and adults, and then conducted simulations to assess the effect of HRF of the power of different stimulation protocols and analysis assumptions (HRF modeling). We found that neonatal fMRI is most powerful if block durations are kept at the lower range of those typically used in adults (full on/off cycle duration 25-30s). Furthermore, we show that it is important to use the age-appropriate HRF during analysis, as mismatches can lead to reduced power or even inverted signal. Where the appropriate HRF is not known (for example due to potential developmental delay), a flexible basis set performs well, and allows accurate post-hoc estimation of the HRF. PMID- 26266956 TI - Who Smells? Forecasting Taste and Odor in a Drinking Water Reservoir. AB - Taste and odor problems can impede public trust in drinking water and impose major costs on water utilities. The ability to forecast taste and odor events in source waters, in advance, is shown for the first time in this paper. This could allow water utilities to adapt treatment, and where effective treatment is not available, consumers could be warned. A unique 24-year time series, from an important drinking water reservoir in Saskatchewan, Canada, is used to develop forecasting models of odor using chlorophyll a, turbidity, total phosphorus, temperature, and the following odor producing algae taxa: Anabaena spp., Aphanizemenon spp., Oscillatoria spp., Chlorophyta, Cyclotella spp., and Asterionella spp. We demonstrate, using linear regression and random forest models, that odor events can be forecast at 0-26 week time lags, and that the models are able to capture a significant increase in threshold odor number in the mid-1990 s. Models with a fortnight time-lag show a high predictive capacity (R(2) = 0.71 for random forest; 0.52 for linear regression). Predictive skill declines for time lags from 0 to 15 weeks, then increases again, to R(2) values of 0.61 (random forest) and 0.48 (linear regression) at a 26-week lag. The random forest model is also able to provide accurate forecasting of TON levels requiring treatment 12 weeks in advance-93% true positive rate with a 0% false positive rate. Results of the random forest model demonstrate that phytoplankton taxonomic data outperform chlorophyll a in terms of predictive importance. PMID- 26266957 TI - Failure to Rescue Metric in Lung Surgery: A Needed Breath of Fresh Air. PMID- 26266958 TI - Chibby functions to preserve normal ciliary morphology through the regulation of intraflagellar transport in airway ciliated cells. AB - Airway cilia provide the coordinated motive force for mucociliary transport, which prevents the accumulation of mucus, debris, pollutants, and bacteria in our respiratory tracts. As airway cilia are constantly exposed to the environment and, hence, are an integral component of the pathogenesis of several congenital and chronic pulmonary disorders, it is necessary to understand the molecular mechanisms that control ciliated cell differentiation and ciliogenesis. We have previously reported that loss of the basal body protein Chibby (Cby) results in chronic upper airway infection in mice due to a significant reduction in the number of airway cilia. In the present work, we demonstrate that Cby is required for normal ciliary structure and proper distribution of proteins involved in the bidirectional intraflagellar transport (IFT) system, which consists of 2 distinct sub-complexes, IFT-A and IFT-B, and is essential for ciliary biogenesis and maintenance. In fully differentiated ciliated cells, abnormal paddle-like cilia with dilated ciliary tips are observed in Cby-/- airways and primary cultures of mouse tracheal epithelial cells (MTECs). In addition, IFT88, an IFT-B sub-complex protein, robustly accumulates within the dilated tips of both multicilia in Cby-/ MTECs and primary cilia in Cby-/- mouse embryonic fibroblasts (MEFs). Furthermore, we show that only IFT-B components, including IFT20 and IFT57, but not IFT-A and Bardet-Biedl syndrome (BBS) proteins, amass with IFT88 in these distended tips in Cby-/- ciliated cells. Taken together, our findings suggest that Cby plays a role in the proper distribution of IFT particles to preserve normal ciliary morphology in airway ciliated cells. PMID- 26266961 TI - Development of low density azithromycin-loaded polycaprolactone microparticles for pulmonary delivery. AB - CONTEXT: The development of low-density polymeric microparticles may be a useful approach to deliver antibiotics such as azithromycin into the lung. OBJECTIVE: The aim of this study was to develop azithromycin-loaded low density polycaprolactone microparticles by the double emulsion/solvent evaporation method. MATERIALS AND METHODS: Microparticles were prepared and characterized according to their physicochemical properties, drug loading, and drug release profiles. A full 23 factorial design was used to evaluate the effect of some independent variables on the drug loading and aerodynamic diameter of the particles. An in silico pulmonary deposition model was used to predict the lung deposition profiles for the formulations. RESULTS AND DISCUSSION: The resulting particles presented drug loading up to 23.1% (wt%) and mean geometric diameters varying from 4.0 um to 15.4 um. Bulk and tapped densities were low, resulting in good or excellent flow properties. SEM images showed spherical particles with a smooth surface. However, hollow inner structures were observed, which may explain the low values of bulk density. The estimated aerodynamic diameters ranged from 2.3 um to 8.9 um. The in silico pulmonary deposition profiles indicated, for some formulations, that a significant fraction of the particles would be deposited in the deeper lung regions. CONCLUSIONS: Statistical analysis demonstrated that not only drug loading but also the aerodynamic diameter of the microparticles is greatly affected by the preparation conditions. Overall, the results indicated that the low-density azithromycin-loaded microparticles with a relatively high respirable fraction may be obtained for the local treatment of lung infections. PMID- 26266959 TI - Minireview: Progesterone Regulation of Proliferation in the Normal Human Breast and in Breast Cancer: A Tale of Two Scenarios? AB - Progesterone (P), which signals through the P receptor (PR), is critical in normal development of the breast, but its signaling axis is also a major driver of breast cancer risk. Here we review recent advances in the understanding of P signaling in the normal human breast, with a focus on the importance of the balance between autocrine and paracrine signaling. To date, most data (which derive largely from mouse models or human breast cancer cell line studies) have demonstrated that the vast majority of PR+ cells appear to act as "sensor" cells, which respond to P stimulation by translating these hormonal cues into paracrine signals. However, growing evidence suggests that, dependent on the cellular context, P may also signal in an autocrine manner in a subset of cells in the normal mouse mammary gland and human breast. It has been suggested that it may be dysregulation of this autocrine signaling, resulting in a "switch" from a predominance of paracrine signaling to autocrine signaling in PR+ cells, which is an early event during breast tumorigenesis. This review summarizes current evidence in the literature that demonstrates the mechanisms through which P acts in the normal human breast, as well as highlighting the important questions that remain unanswered. PMID- 26266960 TI - Age-related increased prevalence of asthma and nasal polyps in chronic rhinosinusitis and its association with altered IL-6 trans-signaling. AB - We report that S100 proteins were reduced in patients with chronic rhinosinusitis (CRS). S100A8/9, which is important in epithelial barrier function, was particularly decreased in elderly patients with CRS. Epithelial expression of S100A8/9 is partly regulated by the IL-6 trans-signaling pathway. The goal of this study was to investigate whether or not age-related reduction of S100A8/9 in CRS is associated with blunting of IL-6 trans-signaling. The levels of IL-6, soluble IL-6 receptor (sIL-6R), soluble gp130 (sgp130), and S100A8/9 from control subjects (n = 10), and patients with CRS without nasal polyps (n = 13) and those with CRS with nasal polyps (CRSwNP) (n = 14), were measured by ELISA. Age-related differences in the level of each protein were investigated. Normal human bronchial epithelial cells were cultured in air-liquid interface and stimulated with IL-6/sIL-6R and tumor necrosis factor (TNF)-alpha with or without the addition of sgp130, a natural inhibitor of IL-6 trans-signaling. There was a significant age-related decline in S100A8/9 and an increase in sgp130 in nasal tissue samples from patients with CRSwNP, although there was no age-related difference in IL-6/sIL-6R production. Additionally, expression of the S100A8/9 gene and protein was increased significantly by IL-6/sIL-6R plus TNF-alpha in normal human bronchial epithelial cells. This increase was blocked by sgp130. These results suggest that increased sgp130 in older patients may inhibit IL-6 trans-signaling, impair barrier function, and decrease S1008/9 production in elderly patients with CRSwNP. Restoration of barrier function by targeting sgp130 may be a novel treatment strategy. PMID- 26266962 TI - Preparation of hydrogel embedded polymer-growth factor conjugated nanoparticles as a diabetic wound dressing. AB - CONTEXT: Growth factors act in an integrated manner to promote the wound-healing process. However, probably due to early inactivation of these molecules in the wound site, their topical administration scarcely leads to a significant improvement in chronic wound repair. OBJECTIVES: With the aim of identifying improved therapeutics, a sodium carboxymethyl chitosan-recombinant human epidermal growth factor conjugate (NaCMCh-rhEGF) was developed. It is believed that conjugation will protect rhEGF against proteolysis and will mediate rhEGF release by alpha-amylase. MATERIAL AND METHODS: As hydrogels possess most of the desirable characteristics of an ideal dressing, we used our previously described chitosan-based hydrogel as a carrier for NaCMCh-rhEGF nanoparticles to make a novel wound dressing system. To evaluate the biological activity of NaCMCh-rhEGF and free rhEGF, the proliferation of fibroblasts was measured using a colorimetric assay. Additionally the stability of conjugated and free rhEGF against proteases was estimated. RESULT AND DISCUSSION: In vitro results revealed that the conjugated form exhibited more stability against proteolysis and also preserved its biological activity. Furthermore, in vivo studies were performed using an excision wound model on diabetic rats. After 15 d, the wound area in NaCMCh-rhEGF-hydrogel dressing group was significantly smaller than other groups and showed histological parameters equal to positive wound control group. CONCLUSION: A polymer conjugated rhEGF was developed that was more stable against proteases and reserved the biological activity of the drug. This dressing appears to be a competent candidate for chronic wound healing. PMID- 26266963 TI - Risk assessment of supply chain for pharmaceutical excipients with AHP-fuzzy comprehensive evaluation. AB - As the essential components in formulations, pharmaceutical excipients directly affect the safety, efficacy, and stability of drugs. Recently, safety incidents of pharmaceutical excipients posing seriously threats to the patients highlight the necessity of controlling the potential risks. Hence, it is indispensable for the industry to establish an effective risk assessment system of supply chain. In this study, an AHP-fuzzy comprehensive evaluation model was developed based on the analytic hierarchy process and fuzzy mathematical theory, which quantitatively assessed the risks of supply chain. Taking polysorbate 80 as the example for model analysis, it was concluded that polysorbate 80 for injection use is a high-risk ingredient in the supply chain compared to that for oral use to achieve safety application in clinic, thus measures should be taken to control and minimize those risks. PMID- 26266964 TI - New trimethyl chitosan-based composite nanoparticles as promising antibacterial agents. AB - In the present study, densely dispersed silver nanoparticles (Ag NPs) were rapidly green synthesized in the presence of Rumex dentatus aqueous extract, followed by UV-irradiation reduction. The Ag NPs were characterized using UV-vis spectroscopy, FTIR, XRD, and TEM. Then, the Ag NPs were incorporated into interpenetrating polymeric networks based on cationic trimethyl chitosan (TMCS) and anionic poly(acrylamide-co-sodium acrylate) copolymer to develop a new series of composite nanoparticles as potential antibacterial agents. Both TMCS and poly(acrylamide-co-sodium acrylate) were prepared in the study, and characterized using FTIR, DSC, and SEM. The synthesized Ag NPs showed high purity and uniform particle size distribution with particle size ranged between 5 and 30 nm. The composite nanoparticles demonstrated homogeneous spherical shape with size in the range of 378-402 nm. Both Ag NPs and the composite nanoparticles showed promising bactericidal activity as compared with the control. Moreover, the antibacterial activity of the composite nanoparticles increased along with increasing the concentrations of Ag NPs and the TMCS. PMID- 26266965 TI - Use of the Flory-Huggins theory to predict the solubility of nifedipine and sulfamethoxazole in the triblock, graft copolymer Soluplus. AB - CONTEXT: Drug dispersed in a polymer can improve bioavailability; dispersed amorphous drug undergoes recrystallization. Solid solutions eliminate amorphous regions, but require a measure of the solubility. OBJECTIVE: Use the Flory Huggins Theory to predict crystalline drugs solubility in the triblock, graft copolymer Soluplus(r) to provide a solid solution. MATERIALS AND METHODS: Physical mixtures of the two drugs with similar melting points but different glass forming ability, sulfamethoxazole and nifedipine, were prepared with Soluplus(r) using a quick technique. Drug melting point depression (MPD) was measured using differential scanning calorimetry. The Flory-Huggins Theory allowed: (1) interaction parameter, chi, calculation using MPD data to provide a measure of drug-polymer interaction strength and (2) estimation of the free energy of mixing. A phase diagram was constructed with the MPD data and glass transition temperature (Tg) curves. RESULTS: The interaction parameters with Soluplus(r) and the free energy of mixing were estimated. Drug solubility was calculated by the intersection of solubility equations and that of MPD and Tg curves in the phase diagram. DISCUSSION: Negative interaction parameters indicated strong drug-polymer interactions. The phase diagram and solubility equations provided comparable solubility estimates for each drug in Soluplus(r). Results using the onset of melting rather than the end of melting support the use of the onset of melting. CONCLUSION: The Flory-Huggins Theory indicates that Soluplus(r) interacts effectively with each drug, making solid solution formation feasible. The predicted solubility of the drugs in Soluplus(r) compared favorably across the methods and supports the use of the onset of melting. PMID- 26266966 TI - Six-coordinate Group 13 complexes: the role of d orbitals and electron-rich multi center bonding. AB - Bonding in six-coordinate complexes based on Group 13 elements (B, Al, Ga, In, Tl) is usually considered to be identical to that in transition-metal analogues. We herein demonstrate through sophisticated electronic-structure analyses that the bonding in these Group 13 element complexes is fundamentally different and better characterized as electron-rich hypervalent bonding with essentially no role for the d orbitals. This characteristic is carried through to the molecular properties of the complex. PMID- 26266967 TI - The Enduring Search for the Koplik Spots of Psychosis. PMID- 26266968 TI - Strong Tunable Visible Absorption Predicted for Polysilo-acenes Using TDDFT Calculations. AB - The optical properties of polysilo-acenes with two to six fused rings are studied using time-dependent density functional theory. We show that there are three spectral features in the absorption spectra analogous to alpha, beta, and p-band peaks known for carbon-based acenes. The beta peak is the most prominent feature in each spectrum, which appears in the visible region. Both alpha and beta peaks originate due to identical transitions that are polarized along the long axis of the system. The constructive interaction of quasi-degenerate configurations gives rise to the strong beta peak, while their destructive interaction results in the alpha peak with a low oscillator strength. Because the constructive interaction of configurations is characteristic of plasmons in acenes and noble metal nanoparticles, the beta peak can be identified as plasmonic for polysilo-acenes. The strong visible absorption and the potential for use in existing Si-technology affirm the interest in polysilo-acenes. PMID- 26266969 TI - Early-Life Environmental Exposures and Height, Hypertension, and Cardiovascular Risk Factors Among Older Adults in India. AB - Environmental exposures like rainfall and temperature influence infectious disease exposure and nutrition, two key early-life conditions linked to later life health. However, few tests of whether early-life environmental exposures impact adult health have been performed, particularly in developing countries. This study examines the effects of experiencing rainfall and temperature shocks during gestation and up through the first four years after birth on measured height, hypertension, and other cardiovascular risk factors using data on adults aged 50 and above (N = 1,036) from the 2007-2008 World Health Organization Study on Global Ageing and Adult Health (SAGE) and district-level meteorological data from India. Results from multivariate logistic regressions show that negative rainfall shocks during gestation and positive rainfall shocks during the postbirth period increase the risk of having adult hypertension and CVD risk factors. Exposure to negative rainfall shocks and positive temperature shocks in the postbirth period increases the likelihood of falling within the lowest height decile. Prenatal shocks may influence nutrition in utero, while postnatal shocks may increase exposure to infectious diseases and malnutrition. The results suggest that gestation and the first two years after birth are critical periods when rainfall and temperature shocks take on increased importance for adult health. PMID- 26266970 TI - Early-Life Conditions, Rapid Demographic Changes, and Older Adult Health in the Developing World. AB - The demographic transition of the 1930s-1960s dramatically improved life expectancy in some developing countries. Cohorts born during this time are increasingly characterized by their survivorship of poor early-life conditions, such as poor nutrition and infectious diseases. As a result, they are potentially more susceptible to the effects of these conditions at older ages. This study examines this conjecture by comparing obesity, diabetes, and hypertension in older adults born in the beginning portion of the 1930s-1960s across different mortality regimes using a subset of harmonized cross-national data from seven low and middle-income countries (RELATE, n = 16,836). Using birthplace and height as indicators of early-life conditions, the results show (1) higher prevalence of obesity and diabetes and higher likelihood of obesity, diabetes, and hypertension in middle-income countries, but (2) no convincing evidence to indicate stronger effects of early-life conditions on health in these countries. However, shorter adults living in urban areas were more likely to be obese, indicating the overall importance of early-life conditions and the potential negative impact of urban exposures during adulthood. Obesity results may foreshadow the health of future cohorts born in the later portion of the 1930s-1960s as they reach older ages (60+). PMID- 26266971 TI - Babies of the War: The Effect of War Exposure Early in Life on Mortality Throughout Life. AB - There is increasing evidence that circumstances very early in our lives, and particularly during pregnancy, can affect our health for the remainder of life. Studies that have looked at this relationship have often used extreme situations, such as famines that occurred during wartime. Here we investigate whether less extreme situations during World War II also affected later-life mortality for cohorts born in Belgium, France, The Netherlands, and Norway. We argue that these occupied countries experienced a considerable deterioration in daily life situations and show that this resulted in strongly increased mortality rates and lower probabilities of survival until age 55 among civilian populations who had been prenatally exposed to wartime circumstances. However, this mortality effect among the prenatally exposed is entirely concentrated in the first years of life, particularly infanthood. Once we condition on having survived the first years of life, those who had been prenatally exposed do not have higher mortality rates. This suggests that "culling" is important and that effects found in earlier studies may have been biased downward substantially. PMID- 26266972 TI - Breakfast Skipping, Extreme Commutes, and the Sex Composition at Birth. AB - A growing body of literature has shown that environmental exposures in the period around conception can affect the sex ratio at birth through selective attrition that favors the survival of female conceptuses. Glucose availability is considered a key indicator of the fetal environment, and its absence as a result of meal skipping may inhibit male survival. We hypothesize that breakfast skipping during pregnancy may lead to a reduction in the fraction of male births. Using time use data from the United States we show that women with commute times of 90 minutes or longer are 20 percentage points more likely to skip breakfast. Using U.S. census data we show that women with commute times of 90 minutes or longer are 1.2 percentage points less likely to have a male child under the age of 2. Under some assumptions, this implies that routinely skipping breakfast around the time of conception leads to a 6 percentage point reduction in the probability of a male child. Skipping breakfast during pregnancy may therefore constitute a poor environment for fetal health more generally. PMID- 26266973 TI - Effects of Birth Month on Child Health and Survival in Sub-Saharan Africa. AB - Birth month is broadly predictive of both under-5 mortality rates and stunting throughout most of sub-Saharan Africa (SSA). Observed factors, such as mother's age at birth and educational status, are correlated with birth month but are not the main factors underlying the relationship between birth month and child health. Accounting for maternal selection via a fixed-effects model attenuates the relationship between birth month and health in many SSA countries. In the remaining countries, the effect of birth month may be mediated by environmental factors. This study found that birth month effects on mortality typically do not vary across age intervals; the differential mortality rates by birth month are evident in the neonatal period and continue across age intervals. The male-to female sex ratio at birth did not vary by birth month, which suggests that in utero exposures are not influencing fetal loss, and that therefore the birth month effects are not likely a result of selective survival during the in utero period. In one-third of the sample, the birth month effects on stunting diminished after the age of 2 years; therefore, some children were able to catch up. Policies to improve child health should target pregnant women and infants and must take seasonality into account. PMID- 26266974 TI - Highly Efficient Thermal and Light-Induced Spin-State Switching of an Fe(II) Complex in Direct Contact with a Solid Surface. AB - Spin crossover (SCO) complexes possess a bistable spin state that reacts sensitively to changes in temperature or excitation with light. These effects have been well investigated in solids and solutions, while technological applications require the immobilization and contacting of the molecules at surfaces, which often results in the suppression of the SCO. We report on the thermal and light-induced SCO of [Fe(bpz)2phen] molecules in direct contact with a highly oriented pyrolytic graphite surface. We are able to switch on the magnetic moment of the molecules by illumination with green light at T = 6 K, and off by increasing the temperature to 65 K. The light-induced switching process is highly efficient leading to a complete spin conversion from the low-spin to the high-spin state within a submonolayer of molecules. [Fe(bpz)2phen] complexes immobilized on weakly interacting graphite substrates are thus promising candidates to realize the vision of an optically controlled molecular logic unit for spintronic devices. PMID- 26266975 TI - PIK3CA(H1047R) induces multipotency and multi-lineage mammary tumours. AB - The adult mouse mammary epithelium contains self-sustained cell lineages that form the inner luminal and outer basal cell layers, with stem and progenitor cells contributing to its proliferative and regenerative potential. A key issue in breast cancer biology is the effect of genomic lesions in specific mammary cell lineages on tumour heterogeneity and progression. The impact of transforming events on fate conversion in cancer cells of origin and thus their contribution to tumour heterogeneity remains largely elusive. Using in situ genetic lineage tracing and limiting dilution transplantation, we have unravelled the potential of PIK3CA(H1047R), one of the most frequent mutations occurring in human breast cancer, to induce multipotency during tumorigenesis in the mammary gland. Here we show that expression of PIK3CA(H1047R) in lineage-committed basal Lgr5-positive and luminal keratin-8-positive cells of the adult mouse mammary gland evokes cell dedifferentiation into a multipotent stem-like state, suggesting this to be a mechanism involved in the formation of heterogeneous, multi-lineage mammary tumours. Moreover, we show that the tumour cell of origin influences the frequency of malignant mammary tumours. Our results define a key effect of PIK3CA(H1047R) on mammary cell fate in the pre-neoplastic mammary gland and show that the cell of origin of PIK3CA(H1047R) tumours dictates their malignancy, thus revealing a mechanism underlying tumour heterogeneity and aggressiveness. PMID- 26266976 TI - Switching on elusive organometallic mechanisms with photoredox catalysis. AB - Transition-metal-catalysed cross-coupling reactions have become one of the most used carbon-carbon and carbon-heteroatom bond-forming reactions in chemical synthesis. Recently, nickel catalysis has been shown to participate in a wide variety of C-C bond-forming reactions, most notably Negishi, Suzuki-Miyaura, Stille, Kumada and Hiyama couplings. Despite the tremendous advances in C-C fragment couplings, the ability to forge C-O bonds in a general fashion via nickel catalysis has been largely unsuccessful. The challenge for nickel-mediated alcohol couplings has been the mechanistic requirement for the critical C-O bond forming step (formally known as the reductive elimination step) to occur via a Ni(III) alkoxide intermediate. Here we demonstrate that visible-light-excited photoredox catalysts can modulate the preferred oxidation states of nickel alkoxides in an operative catalytic cycle, thereby providing transient access to Ni(III) species that readily participate in reductive elimination. Using this synergistic merger of photoredox and nickel catalysis, we have developed a highly efficient and general carbon-oxygen coupling reaction using abundant alcohols and aryl bromides. More notably, we have developed a general strategy to 'switch on' important yet elusive organometallic mechanisms via oxidation state modulations using only weak light and single-electron-transfer catalysts. PMID- 26266978 TI - Biodiversity: Multiple origins of mountain life. PMID- 26266977 TI - The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. AB - Protein aggregates and damaged organelles are tagged with ubiquitin chains to trigger selective autophagy. To initiate mitophagy, the ubiquitin kinase PINK1 phosphorylates ubiquitin to activate the ubiquitin ligase parkin, which builds ubiquitin chains on mitochondrial outer membrane proteins, where they act to recruit autophagy receptors. Using genome editing to knockout five autophagy receptors in HeLa cells, here we show that two receptors previously linked to xenophagy, NDP52 and optineurin, are the primary receptors for PINK1- and parkin mediated mitophagy. PINK1 recruits NDP52 and optineurin, but not p62, to mitochondria to activate mitophagy directly, independently of parkin. Once recruited to mitochondria, NDP52 and optineurin recruit the autophagy factors ULK1, DFCP1 and WIPI1 to focal spots proximal to mitochondria, revealing a function for these autophagy receptors upstream of LC3. This supports a new model in which PINK1-generated phospho-ubiquitin serves as the autophagy signal on mitochondria, and parkin then acts to amplify this signal. This work also suggests direct and broader roles for ubiquitin phosphorylation in other autophagy pathways. PMID- 26266981 TI - Organic chemistry: Light opens pathways for nickel catalysis. PMID- 26266980 TI - SEC14L2 enables pan-genotype HCV replication in cell culture. AB - Since its discovery in 1989, efforts to grow clinical isolates of the hepatitis C virus (HCV) in cell culture have met with limited success. Only the JFH-1 isolate has the capacity to replicate efficiently in cultured hepatoma cells without cell culture-adaptive mutations. We hypothesized that cultured cells lack one or more factors required for the replication of clinical isolates. To identify the missing factors, we transduced Huh-7.5 human hepatoma cells with a pooled lentivirus-based human complementary DNA (cDNA) library, transfected the cells with HCV subgenomic replicons lacking adaptive mutations, and selected for stable replicon colonies. This led to the identification of a single cDNA, SEC14L2, that enabled RNA replication of diverse HCV genotypes in several hepatoma cell lines. This effect was dose-dependent, and required the continuous presence of SEC14L2. Full-length HCV genomes also replicated and produced low levels of infectious virus. Remarkably, SEC14L2-expressing Huh-7.5 cells also supported HCV replication following inoculation with patient sera. Mechanistic studies suggest that SEC14L2 promotes HCV infection by enhancing vitamin E-mediated protection against lipid peroxidation. This provides a foundation for development of in vitro replication systems for all HCV isolates, creating a useful platform to dissect the mechanisms by which cell culture-adaptive mutations act. PMID- 26266982 TI - Cell biology: Tagged tags engage disposal. PMID- 26266983 TI - Structural biology: Lipid gymnastics. PMID- 26266984 TI - Structure and mechanism of an active lipid-linked oligosaccharide flippase. AB - The flipping of membrane-embedded lipids containing large, polar head groups is slow and energetically unfavourable, and is therefore catalysed by flippases, the mechanisms of which are unknown. A prominent example of a flipping reaction is the translocation of lipid-linked oligosaccharides that serve as donors in N linked protein glycosylation. In Campylobacter jejuni, this process is catalysed by the ABC transporter PglK. Here we present a mechanism of PglK-catalysed lipid linked oligosaccharide flipping based on crystal structures in distinct states, a newly devised in vitro flipping assay, and in vivo studies. PglK can adopt inward and outward-facing conformations in vitro, but only outward-facing states are required for flipping. While the pyrophosphate-oligosaccharide head group of lipid-linked oligosaccharides enters the translocation cavity and interacts with positively charged side chains, the lipidic polyprenyl tail binds and activates the transporter but remains exposed to the lipid bilayer during the reaction. The proposed mechanism is distinct from the classical alternating-access model applied to other transporters. PMID- 26266979 TI - Evolution of endemism on a young tropical mountain. AB - Tropical mountains are hot spots of biodiversity and endemism, but the evolutionary origins of their unique biotas are poorly understood. In varying degrees, local and regional extinction, long-distance colonization, and local recruitment may all contribute to the exceptional character of these communities. Also, it is debated whether mountain endemics mostly originate from local lowland taxa, or from lineages that reach the mountain by long-range dispersal from cool localities elsewhere. Here we investigate the evolutionary routes to endemism by sampling an entire tropical mountain biota on the 4,095-metre-high Mount Kinabalu in Sabah, East Malaysia. We discover that most of its unique biodiversity is younger than the mountain itself (6 million years), and comprises a mix of immigrant pre-adapted lineages and descendants from local lowland ancestors, although substantial shifts from lower to higher vegetation zones in this latter group were rare. These insights could improve forecasts of the likelihood of extinction and 'evolutionary rescue' in montane biodiversity hot spots under climate change scenarios. PMID- 26266986 TI - Non-invasive prenatal testing for aneuploidy: a systematic review of Internet advertising to potential users by commercial companies and private health providers. AB - BACKGROUND: The development of non-invasive prenatal testing has increased accessibility of fetal testing. Companies are now advertising prenatal testing for aneuploidy via the Internet. OBJECTIVES: The aim of this systematic review of websites advertising non-invasive prenatal testing for aneuploidy was to explore the nature of the information being provided to potential users. METHODS: We systematically searched two Internet search engines for relevant websites using the following terms: 'prenatal test', 'antenatal test', 'non-invasive test', 'noninvasive test', 'cell-free fetal DNA', 'cffDNA', 'Down syndrome test' or 'trisomy test'. We examined the first 200 websites identified through each search. Relevant web-based text was examined, and key topics were identified, tabulated and counted. To analyse the text further, we used thematic analysis. MAIN RESULTS: Forty websites were identified. Whilst a number of sites provided balanced, accurate information, in the majority supporting evidence was not provided to underpin the information and there was inadequate information on the need for an invasive test to definitely diagnose aneuploidy. CONCLUSIONS: The information provided on many websites does not comply with professional recommendations. Guidelines are needed to ensure that companies offering prenatal testing via the Internet provide accurate and comprehensible information. PMID- 26266985 TI - Reactivation of multipotency by oncogenic PIK3CA induces breast tumour heterogeneity. AB - Breast cancer is the most frequent cancer in women and consists of heterogeneous types of tumours that are classified into different histological and molecular subtypes. PIK3CA and P53 (also known as TP53) are the two most frequently mutated genes and are associated with different types of human breast cancers. The cellular origin and the mechanisms leading to PIK3CA-induced tumour heterogeneity remain unknown. Here we used a genetic approach in mice to define the cellular origin of Pik3ca-derived tumours and the impact of mutations in this gene on tumour heterogeneity. Surprisingly, oncogenic Pik3ca(H1047R) mutant expression at physiological levels in basal cells using keratin (K)5-CreER(T2) mice induced the formation of luminal oestrogen receptor (ER)-positive/progesterone receptor (PR) positive tumours, while its expression in luminal cells using K8-CReER(T2) mice gave rise to luminal ER(+)PR(+) tumours or basal-like ER(-)PR(-) tumours. Concomitant deletion of p53 and expression of Pik3ca(H1047R) accelerated tumour development and induced more aggressive mammary tumours. Interestingly, expression of Pik3ca(H1047R) in unipotent basal cells gave rise to luminal-like cells, while its expression in unipotent luminal cells gave rise to basal-like cells before progressing into invasive tumours. Transcriptional profiling of cells that underwent cell fate transition upon Pik3ca(H1047R) expression in unipotent progenitors demonstrated a profound oncogene-induced reprogramming of these newly formed cells and identified gene signatures characteristic of the different cell fate switches that occur upon Pik3ca(H1047R) expression in basal and luminal cells, which correlated with the cell of origin, tumour type and different clinical outcomes. Altogether our study identifies the cellular origin of Pik3ca-induced tumours and reveals that oncogenic Pik3ca(H1047R) activates a multipotent genetic program in normally lineage-restricted populations at the early stage of tumour initiation, setting the stage for future intratumoural heterogeneity. These results have important implications for our understanding of the mechanisms controlling tumour heterogeneity and the development of new strategies to block PIK3CA breast cancer initiation. PMID- 26266989 TI - Determination of Drugs of Abuse and Their Stereoisomers by Circular Dichroism. AB - More than half of the total drugs in the world are optically active, yet this physical property is all but ignored as an experimental means in drug analysis. Part of the reason may well be that, until recently, regulatory agencies have not required the verification of the absolute stereochemical configuration of a drug molecule. In a forensic context, isomeric confirmations are limited to the recognition of different habits in routine microcrystalline tests. Chirality confirmation is a new regulation introduced by the U.S. Food and Drug Administration for new drug submissions in the pharmaceutical sciences and a rapid, relatively routine procedure is needed. Of the three possible chiroptical detectors that might be used, circular dichroism (CD) has the greatest potential for selectivity and breadth of application with a minimum of sample preparation. The method, once perfected, will be equally invaluable to forensic analyses. Analytical results are reported for a number of drugs of abuse, both enantiomers and diastereoisomers. Chiroptical detection methods are critically compared with chromatographic option. PMID- 26266988 TI - Comprehensive size-determination of whole virus vaccine particles using gas-phase electrophoretic mobility macromolecular analyzer, atomic force microscopy, and transmission electron microscopy. AB - Biophysical properties including particle size distribution, integrity, and shape of whole virus vaccine particles at different stages in tick-borne encephalitis (TBE) vaccines formulation were analyzed by a new set of methods. Size-exclusion chromatography (SEC) was used as a conservative sample preparation for vaccine particle fractionation and gas-phase electrophoretic mobility macromolecular analyzer (GEMMA) for analyzing electrophoretic mobility diameters of isolated TBE virions. The derived particle diameter was then correlated with molecular weight. The diameter of the TBE virions determined after SEC by GEMMA instrumentation was 46.8 +/- 1.1 nm. Atomic force microscopy (AFM) and transmission electron microscopy (TEM) were implemented for comparison purposes and to gain morphological information on the virion particle. Western blotting (Dot Blot) as an immunological method confirmed biological activity of the particles at various stages of the developed analytical strategy. AFM and TEM measurements revealed higher diameters with much higher SD for a limited number of virions, 60.4 +/- 8.5 and 53.5 +/- 5.3 nm, respectively. GEMMA instrumentation was also used for fractionation of virions with specifically selected diameters in the gas-phase, which were finally collected by means of an electrostatic sampler. At that point (i.e., after particle collection), AFM and TEM showed that the sampled virions were still intact, exhibiting a narrow size distribution (i.e., 59.8 +/- 7.8 nm for AFM and 47.5 +/- 5.2 nm for TEM images), and most importantly, dot blotting confirmed immunological activity of the collected samples. Furthermore dimers and virion artifacts were detected, too. PMID- 26266990 TI - Forensic Identification of Explosives by Mass Spectrometry and Allied Techniques. AB - In forensic analysis of explosives, analytical methods are required that combine good separation characteristics with highly specific and sensitive detection. Two novel techniques, liquid chromatography/mass spectrometry (LC/MS) and tandem mass spectrometry (MS/MS) have such specifications. These are now well-established analytical techniques for separation and identification of mixtures and for trace analysis of selected components. The principles and instrumentation of LC/MS and MS/MS are described, as well as their applications, in forensic identification of explosives residues and detection of hidden explosives. PMID- 26266991 TI - A Historical and Comparative Review of the Reception of Forensic Medical and Scientific Evidence under Different Systems of Law. AB - The purpose of this paper is to review the historical basis for the substantial differences which exist between the two main systems of law (common law and civil law) in the reception of forensic medical and scientific evidence by courts of law, and in the medico-legal investigation of sudden deaths in the community. The historical reasons for these differences are explained, and the relevant merits of procedures for presenting expert evidence in the courts of common law and civil law countries are discussed. The early appearance of forensic medical and scientific evidence in continental European (civil law) courts is contrasted with its long delayed introduction into common law countries. Special attention is given to the role of such evidence in the routine investigation of sudden death, which now serves an important public health function. The paper concludes by pointing to the paradox that the civil law countries have succeeded in ensuring that their courts of law receive the best forensic medical and scientific evidence, whilst at the same time failing to ensure that sudden deaths of unexplained cause are adequately investigated. PMID- 26266992 TI - The Interaction of Ethanol with Drugs. AB - Ethanol is perhaps the most widely used drug in society today. Its reactions in the human body are varied and complex but mainly it depresses the central nervous system, which in turn causes a deleterious effect on psychomotor functions. When any of several classes of drugs is introduced into the body along with ethanol, each drug can affect the other's absorption, distribution, metabolism, and excretion. The toxic effects of the drug combination may be potentiated, depending upon several factors such as whether the ingested level of ethanol was acute or chronic, and the pharmacodynamics of the second drug. PMID- 26266993 TI - Methods of Fire Debris Preparation for Detection of Accelerants. AB - Forensic scientists use various techniques to separate accelerants from fire debris samples before instrumental identification of added fuels. Among the choices available, traditional micro-distillation, steam distillation, vacuum distillation, headspace, heated headspace, and several vapor adsorption/desorption methods provide various advantages and disadvantages. This communication reviews the development of these techniques from the 1950s and comparison studies performed. PMID- 26266994 TI - The impact of pain on systemic rheumatic diseases. AB - Pain is associated with the different types of rheumatic syndromes because it is often the most troubling symptom of patients affected by any of these diseases. Some risk factors clearly play a major role in the clinical expression of pain and related syndromes, including genetics, age, gender, co-morbidities, traumas and psychological patterns, but there are no specific clinical, laboratory or neuroimaging markers that can indicate why and when a patient's localised pain will become chronic and widespread. Any type of pain must be treated not only appropriately, but also rapidly because the likelihood of developing some form of chronic pain is related to the duration of the peripheral pain stimulus. Chronic pain inevitably has a major impact on patients' quality of life because the loss of function undermines their ability to do everyday activities. Pain can be most effectively treated by carefully selecting various pharmacological and non pharmacological interventions based on the characteristics of the pain itself, disease factors, psychological coping abilities, and lifestyle. PMID- 26266995 TI - Diagnosing and treating chronic musculoskeletal pain based on the underlying mechanism(s). AB - Until recently, most clinicians considered chronic pain to be typically due to ongoing peripheral nociceptive input (i.e., damage or inflammation) in the region of the body where the individual is experiencing pain. Clinicians are generally aware of a few types of pain (e.g., headache and phantom limb pain) where chronic pain is not due to such causes, but most do not realize there is not a single chronic pain state where any radiographic, surgical, or pathological description of peripheral nociceptive damage has been reproducibly shown to be related to the presence or severity of pain. The primary reason for this appears to be that both the peripheral and central nervous systems play a critical role in determining which nociceptive input being detected by sensory nerves in the peripheral tissues will lead to the perception of pain in humans. This manuscript reviews some of the latest findings regarding the neural processing of pain, with a special focus on how clinicians can use information gleaned from the history and physical examination to assess which mechanisms are most likely to be responsible for pain in a given individual, and tailors therapy appropriately. A critical construct is that, within any specific diagnostic category (e.g., fibromyalgia (FM), osteoarthritis (OA), and chronic low back pain (CLBP) are specifically reviewed), individual patients may have markedly different peripheral/nociceptive and neural contributions to their pain. Thus, just as low back pain has long been acknowledged to have multiple potential mechanisms, so also is this true of all chronic pain states, wherein some individuals will have pain primarily due to peripheral nociceptive input, whereas in others peripheral (e.g., peripheral sensitization) or central nervous system factors ("central sensitization" or "centralization" of pain via augmented pain processing in spinal and brain) may be playing an equally or even more prominent role in their pain and other symptoms. PMID- 26266996 TI - Update on the genetics of the fibromyalgia syndrome. AB - Fibromyalgia syndrome (FMS), a condition characterized by chronic widespread pain and tenderness, is a complex condition considered to represent a paradigm of centralized pain. FMS has demonstrated a clear familial aggregation, and hence it is considered to have a genetic background. Multiple candidate-gene studies have been conducted in this field, focusing on target genes that play a role in the transmission and processing of pain. While many of these have focused in the past on markers related to neurotransmitter systems such as catecholamines (catechol-O methyltransferase (COMT)) and serotonin, novel target genes have recently emerged. In addition, genome-wide sequencing scanning (genome-wide association study (GWAS)) is increasingly being harnessed for the study of chronic pain, including FMS. Micro RNAs are another novel field of research related to posttranscriptional inhibition of gene expression, which are currently regarding the pathogenesis of FMS. PMID- 26266997 TI - Neuroimaging of chronic pain. AB - Chronic pain is an important public health problem, and there is a need to understand the mechanisms that lead to pain chronification. From a neurobiological perspective, the mechanisms contributing to the transition from acute to subacute and chronic pain are heterogeneous and are thought to take place at various levels of the peripheral and central nervous system. In the past decade, brain imaging studies have shed light on neural correlates of pain perception and pain modulation, but they have also begun to disentangle neural mechanisms that underlie chronic pain. This review summarizes important and recent findings in pain research using magnetic resonance tomography. Especially new developments in functional, structural and neurochemical imaging such as resting-state connectivity and gamma-aminobutyric acid (GABA) spectroscopy, which have advanced our understanding of chronic pain and which can potentially be integrated in clinical practice, will be discussed. PMID- 26266998 TI - Pain in systemic inflammatory rheumatic diseases. AB - The sometimes intense, persistent and disabling pain associated with rheumatoid arthritis (RA) and spondyloarthritis frequently has a multifactorial, simultaneously central and peripheral origin, and it may be due to currently active inflammation or joint damage and tissue destruction caused by a previous inflammatory condition. The symptoms of inflammatory pain symptoms can be partially relieved by non-steroidal anti-inflammatory drugs, but many patients continue to experience moderate pain due to alterations in central pain regulation mechanisms, as in the case of the chronic widespread pain (CWP) characterising fibromyalgia. The importance of distinguishing CWP from inflammatory pain is underlined by the fact that drugs such as tumour necrosis factor inhibitors are expensive, and direct costs are higher in patients with concomitant CWP than in those without. The management of pain requires a combination approach that includes pharmacological analgesia, and biological and non-biological treatments because, although joint replacement surgery can significantly improve RA-related pain, it may only be available to patients with the most severe advanced disease. PMID- 26266999 TI - Pain in systemic connective tissue diseases. AB - Pain is frequent in patients with connective tissue diseases (CTDs), particularly those affected by systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) in which it is virtually ubiquitous and can have different causes. The SLE classification criteria include pain associated with musculoskeletal involvement, which are frequently the initial symptom of SLE and can include arthralgia, arthritis and/or myalgia. Chronic widespread pain, the cornerstone of fibromyalgia (FM), is also frequently associated with CTDs. Chronic pain has a considerable impact on mental health, and the professional and family lives of patients. It can be due to many disorders, but there are few reports concerning its prevalence during the course of other diseases. It is essential to identify the origin of pain in CTDs in order to avoid dangerous over-treatment in patients with co-existing widespread pain. Effective pain management is a primary goal of patient care, although it has not been investigated in detail in patients with SSc. PMID- 26267000 TI - Pain in primary Sjogren's syndrome. AB - Joint and muscle pain are commonly observed in patients with primary Sjogren's syndrome (pSS). Different types of pain can be distinguished, that is, articular pain, neuropathic pain and widespread pain. Articular pain is due to more or less evident synovitis, usually involving peripheral joints such as hand joints, wrists, knees and ankles. Drugs used to treat rheumatoid arthritis, or lupus synovitis, are also employed for articular involvement in pSS. Pure sensory neuropathies and, more often, small fibre neuropathies are responsible for neuropathic pain in pSS. This is usually localised in the legs and arms with a characteristic glove or sock distribution. Widespread pain, often assuming the features of fibromyalgia, has also been reported in patients with pSS. The pathological mechanisms underlying both neuropathic pain and widespread (fibromyalgia) pain in pSS have not been so far completely clarified. PMID- 26267001 TI - The words of pain in complex regional pain syndrome. AB - Complex regional pain syndrome (CRPS) encompasses a wide range of painful conditions, but it is characterised by continuing (spontaneous and/or evoked) limb pain that is seemingly disproportionate in time or degree to the usual course of any known trauma or other lesion. The pain is regional, with distal predominance usually but not related to a specific nerve territory or dermatome, and it is usually associated with abnormal sensory, motor, sudomotor, vasomotor and/or trophic findings. The complexity of the aetiopathogenetic factors making up the clinical picture of CRPS is mirrored by the inconsistency of almost all of the monotherapies used to treat it so far. Motor and sensory symptoms significantly interfere with the patients' daily function and quality of life, and almost all of them report substantial disability in their working and recreational activities, mood and mobility. PMID- 26267002 TI - Pain management in cryoglobulinaemic syndrome. AB - Cryoglobulinaemic syndrome (CS) includes clinical signs and symptoms that range from the classic triad of Meltzer and Franklin (purpura, weakness and arthralgias) to multiple organ involvement, and it may be characterised by nociceptive or neuropathic pain. Both types of pain use the same pathways and neurotransmitters, but nociceptive pain has an adaptive system and biological function whereas neuropathic pain does not. Managing CS means dealing with often very different clinical patterns, activity and severity with the aim of preventing irreversible organ damage, reducing pain, improving the patients' quality of life and reducing social costs. However, treatment is still largely empirical, and it is often delayed. The Italian Group for the Study of Cryoglobulinaemia (GISC) strongly recommended a low-antigen-content diet and colchicine for all symptomatic CS patients. Patients with mild-moderate symptoms (such as purpura, weakness, arthralgia and initial neuropathy) have been treated with low or medium doses of steroids, and, in the presence of chronic hepatitis C virus (HCV)-related hepatitis, an attempt has been made to eradicate HCV with pegylated interferon plus ribavirin. In the case of severe or rapidly progressive disease (glomerulonephritis, neuropathy, leg ulcers, widespread vasculitis or hyperviscosity syndrome), more aggressive treatment should be used (e.g., high doses of corticosteroids, plasma exchange plus cyclophosphamide or rituximab). Pain management in CS therefore depends on the type of pain (nociceptive, neuropathic or mixed), the characteristics of the patients and their co morbidities. Drug therapy should be carefully monitored in order to obtain prompt and beneficial results. PMID- 26267003 TI - Osteoarthritis pain. AB - Osteoarthritis (OA) represents one of the most frequently occurring painful conditions. Pain is the major OA symptom, involving both peripheral and central neurological mechanisms. OA pain is initiated from free axonal endings located in the synovium, periosteum bone, and tendons, but not in the cartilage. The nociceptive message involves not only neuromediators and regulating factors such as neuronal growth factor (NGF) but also central modifications of pain pathways. OA pain is a mixed phenomenon where nociceptive and neuropathic mechanisms are involved in both the local and central levels. OA pain perception is influenced by multiple environmental, psychological, or constitutional factors, and OA pain intensity is not correlated with joint degradation. OA pain may present with different clinical features: constant and intermittent pain, with or without a neuropathic component, and with or without central sensitization. Finally, OA pain should be considered as a complex and not unique pain condition, where precise clinical assessment may drive specific therapeutic approaches. PMID- 26267004 TI - Molecular mechanisms of pain in crystal-induced arthritis. AB - Crystal-induced arthritis (CIA) is characterized by an intense inflammatory reaction triggered by the deposition of monosodium urate, calcium pyrophosphate, and basic calcium phosphate crystals in articular and periarticular tissues. Severe, acute pain constitutes the most important clinical symptom in patients affected by these diseases. Pain along with redness, warmness, swelling, and stiffness in the affected joint arises abruptly in gout and disappears when the acute phase of the attack resolves. While an acute joint attack caused by calcium pyrophosphate crystals can mimic a gout flare, basic calcium phosphate crystal arthritis gives rise to a series of clinical manifestations, the most severe of which are calcific periarthritis, mostly asymptomatic, and a highly destructive arthritis known as Milwaukee shoulder syndrome, which is characterized by painful articular attacks. Pain development in CIA is mediated by several inflammatory substances that are formed after cell injury by crystals. The most important of these molecules, which exert their effects through different receptor subtypes present in both peripheral sensory neurons and the spinal cord, are prostaglandins, bradykinin, cytokines (in particular, interleukin (IL)-1beta), and substance P. The pharmacological treatment of pain in CIA is strictly associated with the treatment of acute phases and flares of the disease, during which crystals trigger the inflammatory response. According to international guidelines, colchicines, nonsteroidal anti-inflammatory drugs, and/or corticosteroids are first-line agents for the systemic treatment of acute CIA, while biologics, namely anti-IL-1beta agents, should be used only in particularly refractory cases. PMID- 26267005 TI - "Real-life" treatment of chronic pain: Targets and goals. AB - Treating chronic pain is a complex challenge. While textbooks and medical education classically categorize pain as originating from peripheral (nociceptive), neuropathic, or centralized origins, in real life each and every patient may present a combination of various pain sources, types, and mechanisms. Moreover, individual patients may evolve and develop differing types of pain throughout their clinical follow-up, further emphasizing the necessity to maintain clinical diligence during the evaluation and follow-up of these patients. Rational treatment of patients suffering from chronic pain must attempt at deconstructing complex pain cases, identifying variegate pain generators, and targeting them with appropriate interventions, while incorporating both pharmacological and non-pharmacological strategies, rather than focusing on the total pain level, which represents an integral of all pain types. Failing to recognize the coexistence of different types of pain in an individual patient and escalating medications only on the basis of total pain intensity are liable to lead to both ineffective control of pain and increased untoward effects. In the current review, we outline strategies for deconstructing complex pain and therapeutic suggestions. PMID- 26267007 TI - Meta-analyses of pain studies: What we have learned. AB - Meta-analysis is a statistical procedure that integrates the results of at least two independent studies. The biggest threats to meta-analysis are publication bias due to missing studies with negative results and low-quality evidence due to methodological limitations imposed by included studies. Tools to improve the quality of meta-analysis have been developed by the Cochrane Collaboration and by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Meta-analyses of trials have demonstrated that pain responses in patients with chronic pain, following treatment, are not normally distributed but have a bimodal distribution with the majority of patients having either very little or very good pain relief. The benefit can be detected within 2-4 weeks following drug administration. Further, the efficacy of drug and physical treatments is hampered by high placebo response rates, with modest average benefits with active treatments over placebo in both parallel and crossover design trials. PMID- 26267006 TI - Physical exercise as non-pharmacological treatment of chronic pain: Why and when. AB - Chronic pain broadly encompasses both objectively defined conditions and idiopathic conditions that lack physical findings. Despite variance in origin or pathogenesis, these conditions are similarly characterized by chronic pain, poor physical function, mobility limitations, depression, anxiety, and sleep disturbance, and they are treated alone or in combination by pharmacologic and non-pharmacologic approaches, such as physical activity (aerobic conditioning, muscle strengthening, flexibility training, and movement therapies). Physical activity improves general health, disease risk, and progression of chronic illnesses such as cardiovascular disease, type 2 diabetes, and obesity. When applied to chronic pain conditions within appropriate parameters (frequency, duration, and intensity), physical activity significantly improves pain and related symptoms. For chronic pain, strict guidelines for physical activity are lacking, but frequent movement is preferable to sedentary behavior. This gives considerable freedom in prescribing physical activity treatments, which are most successful when tailored individually, progressed slowly, and account for physical limitations, psychosocial needs, and available resources. PMID- 26267008 TI - Psychological aspects of chronic musculoskeletal pain. AB - Chronic musculoskeletal pain, by its very nature, is associated with negative emotions and psychological distress. There are individual differences in personality, coping skills, behavioral adaptation, and social support that dramatically alter the psychological outcomes of patients with chronic pain. Patients who have an aspect of central pain amplification associated with mechanical or inflammatory pain and patients with fibromyalgia (FM) are likely to exhibit higher levels of psychological distress and illness behaviors. This manuscript discusses several different constructs for the association between chronic pain, central pain amplification, and psychological distress. The first key question addresses mechanisms shared in common between chronic pain and mood disorders, including the individual factors that influence psychological comorbidity, and the second addresses how pain affects mood and vice versa. Finally, the utility of cognitive behavioral approaches in the management of chronic pain symptoms is discussed. PMID- 26267009 TI - Multidisciplinary treatment for rheumatic pain. AB - Chronic pain experienced by patients with rheumatic conditions is recognized to contribute importantly to suffering. Multidisciplinary pain clinics that adhere to the biopsychosocial concept of pain management provide an effective treatment strategy for many with chronic pain. Other than for low back pain and fibromyalgia, little attention has been given to the specific experience of treating those with rheumatic diseases in such a setting. It is, however, reasonable to suggest that many patients with chronic rheumatic pain could benefit from exposure to a multidisciplinary pain treatment programme that incorporates components of education, exercise and activity, as well as psychological techniques and support. Although the specifics of such a treatment will require defining, rheumatologists can look forward to expanded care for their patients with chronic rheumatic pain, and they should be encouraged to become more involved in these clinics. PMID- 26267010 TI - How to measure chronic pain: New concepts. AB - The assessment of chronic pain and its impact on physical, emotional and social functions requires the use of multidimensional qualitative and health-related quality of life instruments, but there is still little agreement concerning what these may be or which approach to adopt. Increasing focus on patient-reported outcomes in medicine has had the positive effect of giving prominence to the views and experiences of patients with chronic pain, and the ecological momentary assessment (EMA) approach allows patients' symptoms to be assessed in their natural environment in real time without the need for recall. Computerised EMA symptom diaries are now generally regarded as the 'gold standard' in the field of pain medicine, and they have recently attracted increasing attention as an essential component of health-care monitoring systems based on the information and communication technology. A web/Internet-based diary and patient terminal seem to provide a ubiquitous, easy-to-use and cost-efficient solution for patient centred data acquisition. In addition, telemonitoring is increasingly seen as an effective means of supporting shared decision-making as it can inform patients about typical symptoms, treatment options and prognosis, and it is widely accepted as an additional source of information. This article reviews some of the instruments used to assess chronic pain, including newly developed and well established validated multidimensional instruments and health-care monitoring systems based on information and communication technology, and it discusses their advantages and limitations. PMID- 26267011 TI - Discovery and Development of Pyridine-bis(imine) and Related Catalysts for Olefin Polymerization and Oligomerization. AB - For over 40 years following the polyolefin catalyst discoveries of Hogan and Banks (Phillips) and Ziegler (Max Planck Institute), chemists traversed the periodic table searching for new transition metal and lanthanide-based olefin polymerization systems. Remarkably, none of these "hits" employed iron, that is, until three groups independently reported iron catalysts for olefin polymerization in the late 1990's. The history surrounding the discovery of these catalysts was only the beginning of their uniqueness, as the ensuing years have proven these systems remarkable in several regards. Of primary importance are the pyridine-bis(imine) ligands (herein referred to as PDI), which produced iron catalysts that are among the world's most active for ethylene polymerization, demonstrated "staying power" despite over 15 years of ligand improvement efforts, and generated highly active polymerization systems with cobalt, chromium, and vanadium. Although many ligands have been employed in iron-catalyzed polymerization, the PDI family has thus far provided the most information about iron's capabilities and tendencies. For example, iron systems tend to be highly selective for ethylene over higher olefins, making them strong candidates for producing highly crystalline polyethylene, or highly linear alpha-olefins. Iron PDI polymerizes propylene with 2,1-regiochemistry via a predominantly isotactic, chain end control mechanism. Because the first insertion proceeds via 1,2 regiochemistry, iron (and cobalt) PDI systems can be tailored to make highly linear dimers of alpha-olefins by "head-to-head" coupling, resulting from a switch in regiochemistry after the first insertion. Finally, PDI ligands, while not being surpassed in activity, have inspired the development of related ligand families and complexes, such as pendant donor diimines (PDD), which are also highly efficient at producing linear alpha-olefins. This Account will detail a variety of oligomerization and polymerization results achieved with PDI and PDD catalysts. Our studies on ligand modification are discussed, but numerous ligands have been synthesized by others. Computational approaches, identification of catalyst active sites, noninnocent ligand studies, commercialization efforts, and other outstanding research are only briefly mentioned, at most. The reader is directed to review articles where appropriate, in order to address the cursory treatment of these areas. PMID- 26267012 TI - Management of hip fractures in older people in Beijing: a retrospective audit and comparison with evidence-based guidelines and practice in the UK. AB - Despite the high burden of hip fracture in China, there is limited information on its management. This study investigated the management of hip fractures in a Beijing tertiary hospital and compared practice with that in 180 hospitals in the UK. The findings show a significant gap exists between the countries. INTRODUCTION: The purpose of this study was to determine if the management of older people with hip fractures in a Beijing tertiary hospital is comparable with the UK best practice guidelines for hip fracture management and the UK National Hip Fracture Database 2012, obtained from 180 hospitals. METHODS: A retrospective audit was undertaken in a large tertiary care hospital in Beijing. Data were compared with the National Hip Fracture Database 2012 collected in 180 hospitals in the UK on the proportion of patients managed according to the UK Blue Book standards. RESULTS: Sixty-six percent of patients were admitted to an orthopaedic ward within 24 h of fracture, while 100 % of patients in the UK were admitted to an orthopaedic ward within 24 h of arrival to an accident and emergency department. Only 8 % of patients received surgery within 48 h of admission compared with 83 % in the UK; 10 % received no surgery compared with 2.5 % in the UK; and 27 % received orthogeriatrician assessment compared with 70 % in the UK. New pressure ulcers developed in 2 % of patients compared with 3.7 % of those in the UK; whereas, 0.3 % of patients were assessed for osteoporosis treatment and 3.8 % received falls assessment, and comparable figures for the UK were 94 and 92 %, respectively. CONCLUSIONS: Significant gaps exist in hip fracture management in the Beijing hospital compared with the best practice achieved in 180 UK hospitals, highlighting the need to implement and evaluate proactive strategies to increase the uptake of best practice hip fracture care in China. PMID- 26267013 TI - Fibrosis markers, hip fracture risk, and bone density in older adults. AB - We examined whether blood levels of two markers of fibrosis (transforming growth factor beta one (TGF-beta1) and procollagen type III N-terminal propeptide (PIIINP)) are related to hip fracture risk and to bone mineral density (BMD). TGF beta1 levels were associated with lower hip fracture risk in women and with lower BMD in men. PIIINP levels were not associated with either outcome. INTRODUCTION: TGF-beta1 serves several roles in bone formation and resorption. A consequence of TGF-beta1 activation is the production of PIIINP, a marker of collagen III deposition. Here, we explore whether these two biomarkers are related to incident hip fracture and bone mineral density (BMD) and whether their associations are modified by systemic inflammation, as measured by C-reactive protein (CRP) levels. METHODS: Participants were from the Cardiovascular Health Study (mean age 78 years; mean follow-up 8.3 years). We included 1681 persons with measured levels of TGF-beta1 (149 hip fractures) and 3226 persons with measured levels of PIIINP (310 hip fractures). RESULTS: Among women, higher TGF-beta1 levels were associated with lower hip fracture risk (HR, per doubling, 0.78 [95 % CI 0.61, 0.91]). Among men, TGF-beta1 levels were associated with hip fracture risk in a non-linear manner, but among those with elevated CRP levels, doubling was associated with increased risk of fracture (HR 2.22 [1.20, 4.08]) (p = 0.02, interaction between low and high CRP and TGF-beta1 on fracture risk). TGF-beta1 levels had no significant association with total hip or total body BMD in women but were significantly associated with lower BMD in men. There were no associations of PIIINP levels with hip fracture risk or BMD in men or women. CONCLUSIONS: TGF-beta1 levels appear to be associated with bone-related phenotypes in a sex-specific manner. The reasons for these differences between men and women regarding TGF-beta1 levels and hip fracture risk and bone density require further investigation. PMID- 26267014 TI - The gene expression profiling of hepatocellular carcinoma by a network analysis approach shows a dominance of intrinsically disordered proteins (IDPs) between hub nodes. AB - We have analyzed the transcriptomic data from patients with hepatocellular carcinoma (HCC) after viral HCV infection at the various stages of the disease by means of a networking analysis using the publicly available E-MTAB-950 dataset. The data was compared with those obtained in our group from HepG2 cells, a cancer cell line that lacks the viral infection. By sequential pruning of data, and also taking into account the data from cells of healthy patients as blanks, we were able to obtain a distribution of hub genes for the various stages that characterize the disease and finally, we isolated a metabolic sub-net specific to HCC alone. The general picture is that the basic organization to energetically and metabolically sustain the cells in both the normal and diseased conditions is the same, but a complex cluster of sub-networks controlled by hub genes drives the HCC progression with high metabolic flexibility and plasticity. In particular, we have extracted a sub-net of genes strictly correlated to other hub genes of the network from HepG2 cells, but specific for the HCC and mainly devoted to: (i) control at chromatin levels of cell division; (ii) control of ergastoplasmatic stress through protein degradation and misfolding; (iii) control of the immune response also through an increase of mature T-cells in the thymus. This sub-net is characterized by 26 hub genes coding for intrinsically disordered proteins with a high ability to interact with numerous molecular partners. Moreover, we have also noted that periphery molecules, that is, with one or very few interactions (e.g., cytokines or post-translational enzymes), which do not have a central role in the clusters that make up the global metabolic network, essentially have roles as information transporters. The results evidence a strong presence of intrinsically disordered proteins with key roles as hubs in the sub networks that characterize the various stages of the disease, conferring a structural plasticity to the net nodes but an inherent functional versatility to the whole metabolic net. Thus, our present article provides a novel way of targeting the intrinsic disorder in HCC networks to dampen the cancer effects and provides new insight into the potential mechanisms of HCC. Taken together, the present findings suggest novel targets to design strategies for drug design and may support a rational intervention in the pharmacotherapy of HCC and other associated diseases. PMID- 26267015 TI - Ethnic differences in peanut allergy patterns in South African children with atopic dermatitis. AB - BACKGROUND: The prevalence of peanut allergy in South Africa is unknown, but previously thought to be low, particularly in black South Africans. This study aimed to determine the prevalence of component patterns and predictive values of screening tests in peanut allergy in South African children with atopic dermatitis (AD). METHODOLOGY: This was a prospective, observational study in a pediatric university hospital in Cape Town. Children with AD, aged 6 months to 10 years, were recruited randomly. They were assessed for sensitization and allergy to peanut by questionnaire, skin prick tests (SPT), Immuno Solid Phase Allergen Chip test, ImmunoCAP component tests to Ara h 1, 2, 3, 8, and 9, and incremental food challenges. RESULTS: A total of 100 participants (59 black Africans and 41 of mixed race) were enrolled, median age 42 months. There was a high and comparable rate of peanut sensitization in both black African (41%) and mixed race patients (50%), but a significantly lower prevalence of peanut allergy in the black African group (15% vs. 38%, p = 0.01). The component Ara h 2 was the most useful in differentiating allergy from tolerance in both ethnic groups, but had a significantly lower predictive value for peanut allergy in blacks (53%) vs. mixed race (93%). Overall, SPT and Ara h 2 produced the highest area under the receiver operating characteristic curve. A total of 95% positive predictive values (PPV) for SPT, peanut-specific IgE, and Ara h 2 levels varied significantly between the two ethnic groups. CONCLUSION: The prevalence of peanut allergy is high in South African children with AD, but significantly lower in blacks compared to mixed race patients. The component Ara h 2 is useful for differentiating allergy from tolerance in both ethnic groups. Ninety-five% PPV for peanut allergy tests may need to be revised by ethnic group. PMID- 26267016 TI - Molecular Catalysis of the Electrochemical and Photochemical Reduction of CO2 with Earth-Abundant Metal Complexes. Selective Production of CO vs HCOOH by Switching of the Metal Center. AB - Molecular catalysis of carbon dioxide reduction using earth-abundant metal complexes as catalysts is a key challenge related to the production of useful products--the "solar fuels"--in which solar energy would be stored. A direct approach using sunlight energy as well as an indirect approach where sunlight is first converted into electricity could be used. A Co(II) complex and a Fe(III) complex, both bearing the same pentadentate N5 ligand (2,13-dimethyl-3,6,9,12,18 pentaazabicyclo[12.3.1]octadeca-1(18),2,12,14,16-pentaene), were synthesized, and their catalytic activity toward CO2 reduction was investigated. Carbon monoxide was formed with the cobalt complex, while formic acid was obtained with the iron based catalyst, thus showing that the catalysis product can be switched by changing the metal center. Selective CO2 reduction occurs under electrochemical conditions as well as photochemical conditions when using a photosensitizer under visible light excitation (lambda > 460 nm, solvent acetonitrile) with the Co catalyst. In the case of the Fe catalyst, selective HCOOH production occurs at low overpotential. Sustained catalytic activity over long periods of time and high turnover numbers were observed in both cases. A catalytic mechanism is suggested on the basis of experimental results and preliminary quantum chemistry calculations. PMID- 26267017 TI - Luminescence properties of some monomeric and dimeric cycloplatinated(ii) complexes containing biphosphine ligands. AB - The starting complexes [PtCl(C^N)(dmso)], in which C^N is either ppy = 2 phenylpyridinate, , or bhq = 7,8-benzo[h]quinolinate, , were prepared by a known method using the reaction of [PtCl2(dmso)2] with ppyH or bhqH, respectively, in toluene under reflux conditions. The reaction of [PtCl(C^N)(dmso)], or , with 1 equiv. of a number of biphosphine ligands, P^P, gave the cationic monomeric complexes [Pt(ppy)(P^P)]Cl, for which P^P is either 1,2 bis(diphenylphosphino)ethane (dppe), , 1,3-bis(diphenylphosphino)propane (dppp), , or bis(diphenylphosphino)methane (dppm), ; the bhq analogous complex [Pt(bhq)(dppe)]Cl, , was prepared similarly. However, the complex [Pt(ppy)(dfppe)]Cl, , in which dfppe is 1,2 bis(dipentafluorophenylphosphino)ethane, was prepared by the reaction of with excess amount of dfppe. When each of the starting complexes [PtCl(C^N)(dmso)], or , were reacted with 0.5 equiv. of any of the P^P ligands, the dimeric complexes [Pt2Cl2(ppy)2(MU-P^P)], , or [Pt2Cl2(bhq)2(MU-P^P)], , were formed. The complexes were fully characterized using multinuclear ((1)H and (31)P) NMR spectroscopy and elemental analysis. The structures of typical complexes , , , and were also confirmed by X-ray crystallography. The effect of ligands on the luminescent properties of the complexes was investigated and DFT calculations were performed to confirm the assignments. PMID- 26267018 TI - Toward an Enhancement of the Photoactivity of Multiphotochromic Dimers Using Plasmon Resonance: A Theoretical Study. AB - Building dimers of organic photochromic compounds paves the way to multifunctional switches, but such architectures often undergo partial photoreactivity only. Combining photochromism of molecules and plasmon resonance of gold nanoparticles (NPs) is known to affect the photochromism of monomers, yet the impact on multimers remains unknown. Here we propose a theoretical study of dimers of dithienylethenes by the mean of a hybrid calculation scheme (discrete interaction model/quantum mechanics). We aim to assess how the optical properties of multiphotochromes are tuned by the influence of the plasmon resonances. We show that, for a typical chemisorption orientation on the NP, the absorption bands responsible for the photochromism are significantly enhanced for both the doubly open and mixed closed-open isomers of the dyad, hinting that plasmon resonance could be used to boost the generally poor photoactivity of dithienylethene dyads. PMID- 26267020 TI - Does the Prostatic Urethral Lift Change the BPH Treatment Paradigm? PMID- 26267019 TI - Neuroinformatics Software Applications Supporting Electronic Data Capture, Management, and Sharing for the Neuroimaging Community. AB - Accelerating insight into the relation between brain and behavior entails conducting small and large-scale research endeavors that lead to reproducible results. Consensus is emerging between funding agencies, publishers, and the research community that data sharing is a fundamental requirement to ensure all such endeavors foster data reuse and fuel reproducible discoveries. Funding agency and publisher mandates to share data are bolstered by a growing number of data sharing efforts that demonstrate how information technologies can enable meaningful data reuse. Neuroinformatics evaluates scientific needs and develops solutions to facilitate the use of data across the cognitive and neurosciences. For example, electronic data capture and management tools designed to facilitate human neurocognitive research can decrease the setup time of studies, improve quality control, and streamline the process of harmonizing, curating, and sharing data across data repositories. In this article we outline the advantages and disadvantages of adopting software applications that support these features by reviewing the tools available and then presenting two contrasting neuroimaging study scenarios in the context of conducting a cross-sectional and a multisite longitudinal study. PMID- 26267021 TI - Legends in Urology. PMID- 26267022 TI - Delivering better care and value in urological procedures. PMID- 26267023 TI - Estimating high-risk castration resistant prostate cancer (CRPC) using electronic health records. AB - INTRODUCTION: Canadian guidelines define castration-resistant prostate cancer (CRPC) at high risk of developing metastases using PSA doubling time (PSADT) < 8 months, whereby men may be offered more frequent bone scans/imaging. We evaluated PSA data from nonmetastatic (M0) prostate cancer patients treated at urology and oncology clinics across the United States (US) to describe the proportion and characteristics of patients who met CRPC and high-risk criteria. MATERIALS AND METHODS: We identified M0 prostate cancer patients aged = 18 years receiving androgen deprivation therapy (ADT) in 2011 from electronic health records (EHR), covering 129 urology and 64 oncology practices across the US. We estimated the proportion of prostate cancer patients with evidence of CRPC (consecutive rising PSAs) and subsets that may be at high risk (using several PSA and PSADT cut points). RESULTS: Among 3121 M0 prostate cancer patients actively treated with ADT, 1188 (38%) had evidence of CRPC. Of these, 712 (60%) qualified as high risk in 2011 based on PSADT < 8 months (equivalent to = 8 months in these data). Men = 65 years were more likely to have evidence of CRPC than younger men, although younger men were more likely to have evidence of high-risk disease. CRPC was more common among men receiving ADT in the oncology setting than the urology setting (48% versus 37%). CONCLUSIONS: In this large EHR study with patient-level PSA data, 38% of men with M0 prostate cancer treated with ADT had CRPC. Approximately 60% of M0 CRPC patients may experience a PSADT of < 8 months. These findings require validation in a Canadian patient population. PMID- 26267024 TI - Changing trends in utilization of neoadjuvant chemotherapy in muscle-invasive bladder cancer. AB - INTRODUCTION: To reassess use of perioperative chemotherapy in muscle-invasive bladder cancer (MIBC) following implementation of monthly multidisciplinary meetings to facilitate optimal oncologic treatment. We previously reported from 2003 to 2008 17% of eligible patients with bladder cancer received cisplatin based neoadjuvant chemotherapy (NAC) at our institution. MATERIALS AND METHODS: A retrospective review of all patients who underwent radical cystectomy (RC) between 2008 and 2012 was performed. Information on clinical and pathologic stage, renal function, perioperative chemotherapy (CTX) use and oncologic outcomes was collected. Rationale for utilization decisions was obtained from physician encounter notes. Primary outcome was use of CTX among eligible patients. Secondary measures were type of CTX, pathologic and survival outcomes. RESULTS: Among 261 patients undergoing RC for bladder cancer, 162 were eligible for NAC. Overall 40.7% (n = 66) received NAC, and 86.4% were given platinum. Patients given NAC were younger and had more advanced clinical stage. The degree of chronic kidney disease (CKD) (0-3) did not impact likelihood of receiving NAC. NAC patients were more likely to be downstaged to non-muscle-invasive disease (21.2% versus 7.3% p < 0.01) or have a complete pathologic response (12.1% versus 3.1% p = 0.025). Receipt of NAC did not affect oncologic outcomes. Following RC 22.3% of high risk patients (n = 112) received adjuvant chemotherapy (AC). CONCLUSIONS: Our use of cisplatin-based NAC improved from 17% to 35% and overall utilization of NAC increased from 22% to 41%. NAC led to improved pT0 rates and increased pathologic downstaging. The degree of CKD (0-3) did not impact likelihood of receiving NAC. AC use decreased in part due to higher utilization of NAC. PMID- 26267025 TI - Single instillation of mitomycin C plus bacillus Calmette-Guerin (BCG) versus BCG alone in high grade non-muscle invasive bladder cancer. AB - INTRODUCTION: This study sought to determine if the addition of perioperative mitomycin C (MMC) to treatment with bacillus Calmette-Guerin (BCG) after transurethral resection (TURBT) is superior to TURBT plus BCG alone in high grade non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: Data for 719 patients diagnosed with NMIBC at the University of Pennsylvania Health System between 1977 and 2009 was reviewed retrospectively. Of these patients, 120 had high grade disease and were treated with either BCG alone or with a single instillation of 40 mg of MMC perioperatively in addition to BCG and were thus included in our study. The primary endpoints of this study included recurrence free survival, overall and disease-free survival as assessed via Kaplan-Meier analysis. RESULTS: Of the 120 patients identified who received treatment for high grade NMIBC, 97 were treated with BCG alone and 23 received a single instillation of perioperative MMC in addition to BCG. There were no statistically significant differences noted in demographic or pathologic variables. Patients were followed for a median of 4.5 years and a maximum of 21.8 years, with no differences demonstrated in recurrence-free survival (p = 0.75), overall survival (p = 0.93) or disease-free survival (p = 0.76). Both lack of lymphovascular invasion and BCG maintenance therapy reached significance as independent predictors of recurrence free survival (p = 0.19 and p = 0.28). CONCLUSIONS: While our study indicates that perioperative MMC likely offers little benefit in regards to recurrence or survival in high grade NMIBC, at this point in time, a larger scale, randomized, controlled trial is needed to adequately address this question. PMID- 26267026 TI - Minimally invasive post-chemotherapy retroperitoneal lymph node dissection for nonseminoma. AB - INTRODUCTION: We present our experience with minimally-invasive retroperitoneal lymph node dissection (MI-RPLND) in the post-chemotherapy (PC) setting for residual masses in patients with nonseminoma. MATERIALS AND METHODS: Nineteen men who underwent PC MI-RPLND (14--laparoscopic, 5--robotic) for low-volume residual disease (no more than 5 clinically enlarged retroperitoneal masses, size < 5 cm, no adjacent organ or vascular invasion) between 2006 and 2011 were identified. Clinicodemographic information and pathological outcomes were reported. RESULTS: Median age of our study population was 32 (interquartile range [IQR]: 28-39). Most patients presented with clinical stage II disease (63%) and were categorized as good risk (90%) by the International Germ Cell Consensus Classification. Median size of residual masses on PC imaging was 2.1 cm (IQR: 1.7-3). Full template bilateral RPLND was completed in 53% of cases, and modified left-sided RPLND in 47%. Median operative time was 370 minutes (IQR: 320-420), and median estimated blood loss was 300 cc (IQR: 150-450). Median length of stay was 3 days (IQR: 2-3). Five patients (26%) experienced a postoperative 30 day complication, but none were higher than Clavien grade II. On final pathology, median number of lymph nodes removed was 12 (IQR: 8-23), and 8 patients (42%) had residual teratoma. No patient experienced a recurrence at median follow up of 24 months (IQR: 5-76). CONCLUSIONS: PC MI-RPLND is a feasible option in a select group of patients with acceptable patient morbidity and short-term outcomes. Longer follow up is required to determine the oncologic efficacy of this approach. PMID- 26267027 TI - Significance of cystoscopic bladder trabeculations in women undergoing midurethral sling. AB - INTRODUCTION: To determine the significance of bladder trabeculations seen on preoperative cystoscopy prior to midurethral sling surgery with respect to lower urinary tract symptoms and sling outcomes. MATERIALS AND METHODS: This retrospective study included women with preoperative cystoscopy who underwent midurethral slings for urinary incontinence from 2006-2009. Cystoscopic findings of bladder trabeculations, as well as pre and postoperative urinary symptoms were recorded. Patients with and without bladder trabeculations were compared with respect to baseline characteristics, lower urinary tract symptoms, and sling outcomes. RESULTS: Of the 241 women included in the study, 14.9% had trabeculations on preoperative cystoscopy. At baseline, women with trabeculations were more likely to be older (64.8 years versus 57.8 years, p < 0.01), and have lower mean maximum cystometric capacity (341 mL +/- 136 versus 436 mL +/- 148, p < 0.01), compared to those without trabeculations. More women with trabeculations had mixed incontinence (p < 0.01) and less pure stress incontinence (p < 0.01) preoperatively. There was no difference between women with and without trabeculations with respect to pre and postoperative symptoms of urgency, frequency, and nocturia. Women with preoperative trabeculations were more likely to have preoperative treatment with anticholinergics (p = 0.02) and had a three times higher risk of postoperative sling failure (HR 2.95 [CI 1.11-7.85], p = 0.03). CONCLUSIONS: Preoperative cystoscopic bladder trabeculations are associated with significantly higher rate of midurethral sling failure. Trabeculations were not associated with pre or postoperative lower urinary tract symptoms. PMID- 26267028 TI - The UroCuff test: a non-invasive alternative to pressure flow studies in adult males with lower urinary tract symptoms secondary to bladder outlet obstruction. AB - INTRODUCTION: To assure that patients with lower urinary tract symptoms (LUTS) benefit from interventions, urologists must practice careful selection of surgical candidates. Currently, 15%-30% of men do not benefit optimally from these invasive and potentially morbid procedures. Success rates following transurethral resection of the prostate (TURP) are higher if bladder outlet obstruction (BOO) is confirmed prior to the procedure by invasive pressure flow studies (PFS). However, PFS may not be performed because of many reasons. We report a study of a non-invasive method of assessing BOO. MATERIALS AND METHODS: The UroCuff test was compared to invasive urodynamic studies in adult males with lower urinary tract symptoms. Patients undergoing PFS for LUTS presumed to be due to BOO were recruited from a single site to perform a penile cuff test (UroCuff) at the same time as PFS. Standard PFS were performed followed immediately by a penile cuff test in the same test setting. The results were compared using basic statistical analysis. RESULTS: A total of 19 men were evaluated by both PFS and UroCuff evaluation. Using PFS as the gold standard, the positive predictive value of the UroCuff penile cuff test to diagnose BOO was found to be 92%. The sensitivity of the UroCuff test for detecting BOO was 75%. When compared to PFS, patients preferred the UroCuff 100% of the time. CONCLUSIONS: The UroCuff test is accurate in predicting BOO when compared to conventional invasive pressure flow studies in men with LUTS. It is well tolerated and preferred over invasive pressure flow studies. PMID- 26267029 TI - '7-flap' perineal urethrostomy: an effective option for obese men with devastated urethras. AB - INTRODUCTION: To present an updated experience using our previously reported lateral perineal '7-flap' technique for perineal urethrostomy (PU), highlighting its role in a variety of patients with advanced urethral stricture disease. MATERIALS AND METHODS: All patients who underwent 7-flap PU from 2009-2013 were reviewed. PU was constructed by advancing a "7"-shaped laterally based perineal skin flap into a spatulated, amputated bulbomembranous urethra. The contralateral side of the amputated proximal urethra was then matured to the advanced perineal skin. Patients were stratified by body mass index (BMI) and outcomes were compared. RESULTS: Among 748 patients undergoing urethroplasty during the study period, 22 men (2.9%; mean age 61, range 31-80) received a 7-flap PU for advanced stricture disease (mean follow up 32 months). A majority of patients (14/22, 64%) were obese (BMI = 30). Disease etiologies consisted primarily of lichen sclerosus (9/22, 41%) while 6/22 (27%) had failed prior urethral reconstructions elsewhere. Mean operative time was 108 min (range 54-214), mean estimated blood loss (EBL) was 76 cc (30-200), and all patients were discharged immediately after surgery. Urethrostomy creation was possible in all patients regardless of BMI (mean 33, range 22-43), and there were no differences with regards to EBL (p = 0.71), operative time (p = 0.38), or success rate (p = 0.76) in obese versus non-obese patients undergoing 7-flap PU. Nearly all patients (21/22, 95%) are voiding spontaneously on follow up without the need for any additional procedure. CONCLUSION: In our updated experience, performance of 7-flap urethrostomy has resulted in durable long term success with acceptable performance in technically challenging cases. PMID- 26267030 TI - Robot-assisted renal tumor enucleo-resection in patients with a solitary kidney. AB - INTRODUCTION: Nephron-sparing surgery is most crucial for patients with a small renal mass in a solitary kidney. Historically, a minimally invasive approach in this setting has been discouraged. Tumor enucleo-resection, long established in the management of hereditary renal tumor syndromes, is currently being evaluated as a viable surgical technique in the sporadic renal cell carcinoma (RCC) population. This approach may significantly reduce or eliminate the need for hilar clamping. We sought to evaluate our experience with robot-assisted enucleo resection partial nephrectomy (EN-RAPN) in patients with solitary kidneys. MATERIALS AND METHODS: Records of patients with a solitary kidney requiring partial nephrectomy performed with robot-assisted enucleo-resection technique at four academic institutions between 2010 and 2013 were reviewed. Baseline demographic, perioperative and pathological data were collected. Functional and early operative outcomes were analyzed. RESULTS: Twelve patients underwent EN RAPN with a median age of 68 years (range 55-80) and follow up duration of 12.55 months (IQR: 5.25, 18.88). Median warm ischemia time was 5.5 minutes (IQR: 0, 13.25) with 6/12 (50%) done off-clamp (zero warm ischemia). Ten (83.3%) patients were pT1a and clear cell was the predominant pathology (9 patients, 75%). Surgical margins were negative in all patients. No patient experienced renal loss or required dialysis. Pre and postoperative estimated glomerular filtration rate (eGFR) at last follow up was similar (54.3, 48.9, Delta-7.0%; p = 0.313). CONCLUSIONS: Robot-assisted enucleo-resection partial nephrectomy in patients with a solitary kidney appears safe and feasible in our early experience. This approach may be utilized to maximize renal preservation and minimize hilar clamping in this setting. PMID- 26267031 TI - Alpha blocker monotherapy versus combination therapy with antimuscarinics in men with persistent LUTS refractory to alpha-adrenergic treatment: patterns of persistence. AB - INTRODUCTION: Patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) often present with voiding and storage symptoms, which may require combination therapy with an alpha blocker and an antimuscarinic (AM). This study compared treatment persistence in LUTS/BPH patients on alpha blocker monotherapy with those using combination alpha blocker and AM therapy (AB/AM). MATERIALS AND METHODS: Retrospective analysis of anonymized patient longitudinal prescription reimbursement claims data. All patients who had claims for any of four alpha blocker medications and six AM agents during an index period from April 1, 2011 to March 31, 2012 were included. For the combination therapy group, the effect of adherence with the AM medication on persistence to the alpha blocker was examined. RESULTS: Patients on AB/AM combination therapy remained on alpha blockers for longer than those on alpha blocker monotherapy (p = 0.04); 92.4% were persistent at 3 months versus 89.0%, and at 1 year 50.8% were persistent versus 49.6%, respectively. The highest number of days on therapy was reported for tamsulosin plus solifenacin. As confirmed by multivariate analysis, patients with the highest adherence to AM medication (= 80%) persisted on alpha blockers for longer than those with the lowest (< 50%) adherence (p < 0.05). CONCLUSIONS: Patients taking an AM in combination with an alpha blocker showed greater persistence with alpha blocker treatment over a 1 year period. When an AM is combined with an alpha blocker in patients with LUTS/BPH, the additional medication burden does not have a negative impact on persistence and may even improve it. PMID- 26267032 TI - Pediatric emphysematous cystitis: a report and review of a rare diagnosis in children. AB - An 11-year-old female with spastic quadriplegia was seen in the emergency room with abdominal pain, vomiting and anorexia. Labs revealed possible pancreatitis and signs of a urinary tract infection. A CT scan was performed to assess her abdominal pain and demonstrated circumferential air within the bladder wall. Following cultures being drawn, she was started on broad spectrum antibiotics. Her urine eventually grew Klebsiella Pneumoniae. Follow up imaging 2 weeks later demonstrated resolution of the air. Emphysematous cystitis is an exceedingly rare condition in the pediatric population, with this report representing the second case within the literature. PMID- 26267033 TI - Femoral hernias in the pediatric patient: a case report and review of the literature. AB - We report a case of a femoral hernia in a 9-year-old male. Femoral hernias in children are rare and a diagnostic challenge. Definitive treatment is with surgical repair. PMID- 26267034 TI - Primary renal extra-osseous osteosarcoma. AB - Primary renal extra-osseous osteosarcoma is an exceedingly rare and deadly kidney neoplasm with only 27 reported cases to date. Extra-osseous osteosarcoma is a mesenchymal sarcoma that produces osteoid, but has no skeletal or periosteal involvement and most commonly arises in the lower extremities. Yet, it can arise in other locations such as the kidney. Extra-osseous osteosarcoma behaves as a separate entity from osseous osteosarcoma and should be treated as such. The treatment is surgical resection. Five year overall survival is 46% for local and 10% for metastatic disease. Additionally, 45%-50% of patients experience disease recurrence. We present a 77-year-old woman who underwent work up for recurrent gross hematuria and subsequently underwent radical nephroureterectomy for presumed upper tract urothelial cell carcinoma. However, pathologic analysis revealed a diagnosis of primary renal extra-osseous osteosarcoma. She is alive with no evidence of disease 30 months after surgery. PMID- 26267035 TI - Penoscrotal lymphedema associated with metastatic renal cell carcinoma. AB - A 64-year-old male presented with lower back pain, radiating in a sciatic-type distribution, swelling in his lower abdomen and right leg, and edema of the scrotum and penile shaft. A sonogram and CT imaging indicated an enhancing mass in the right kidney and a spinal metastasis. The right lower extremity and penoscrotal lymphedema was caused by lymphatic obstruction due to a sacral metastasis of renal cell carcinoma. He was treated with cytoreductive nephrectomy, radiation and a systemic tyrosine kinase inhibitor. Pelvic imaging is suggested to determine whether malignant lymphatic obstruction is present when presented with idiopathic penoscrotal edema. PMID- 26267036 TI - The case of the shrinking testis. AB - We report the case of a man with idiopathic lymphocytic orchitis (LO) manifested by undifferentiated testicular pain and atrophy. Conventional investigation results were unremarkable. Oral ciprofloxacin only improved the pain temporarily. Scrotal exploration surgery was performed to exclude acute testicular torsion and a biopsy was taken during surgery for histological examination. Histology revealed severe LO with reduced spermatogenesis. A trial of oral steroids was initially effective but the effect was temporary. Due to chronic pain, he eventually underwent unilateral orchidectomy. Histology confirmed the initial diagnosis of LO. He was pain-free postoperatively. Idiopathic LO is a rarely reported cause of testicular atrophy. PMID- 26267037 TI - Acupuncture for hot flashes in men treated with androgen deprivation therapy. AB - In men with advanced carcinoma of the prostate being treated with androgen deprivation therapy (ADT), hot flashes can be a significant side effect of the treatment. In this paper we describe using acupuncture as a complementary alternative therapy for treatment of hot flashes in men. PMID- 26267038 TI - Is Postpartum Depression a Distinct Disorder? AB - The nosology of postpartum depression (PPD) is controversial. We review the evidence and arguments for and against the recognition of PPD as a distinct disorder and discuss the etiopathogenic and diagnostic validity of PPD as a distinct disorder, including its utility and indications for further research. Although multiple epidemiological and clinical studies have found that depression is more common following childbirth than at other times in a woman's life, there is conflicting evidence for the validity of PPD as a distinct disorder. PPD is likely to be a complex phenotype, encompassing several disorders with different disease pathways. It is plausible that for a sub-group of vulnerable women, childbirth triggers episodes of depression. However, even within this group, the mechanisms underpinning the mood disturbances are likely complex and heterogeneous. The distinction between depression occurring in the perinatal period and depression at other times is important for both research and clinical practice. Research should differentiate between episodes that begin during pregnancy and postpartum, as the pathogenetic factors involved may differ and require specialized treatment. PMID- 26267039 TI - Evaluation of DNA methyltransferase activity and inhibition via chiroplasmonic assemblies of gold nanoparticles. AB - Circular dichroism spectroscopy has been explored for detection of methyltransferase activity and inhibition based on DNA-induced chiroplasmonic assemblies of gold nanoparticles and endonuclease HpaII. Good accuracy, precision and sensitivity are obtained in complex matrices such as human serum samples, which is significant for clinical diagnosis and drug development. PMID- 26267040 TI - The potential versus current state of water splitting with hematite. AB - This review describes the potential of hematite as a photoanode material for photoelectrochemical (PEC) water splitting. The current understanding of key loss mechanisms of hematite are introduced and correlated to performance enhancement strategies. The significant voltage loss associated with overcoming the competitive water oxidation and surface state recombination has recently been surmounted through a combination of high temperature annealing and surface modification with water oxidation catalysts. Substantial efforts have been made at nanostructuring electrodes to increase the charge separation efficiency without sacrificing light absorption. Even in optimized nanostructured electrodes, however, charge separation continues to be the primary barrier to achieving efficient water splitting with hematite. Specifically, significant depletion region recombination results in voltage dependant photocurrent which constrains the fill factor. Thus, future directions to enhance the efficiency of hematite electrodes are discussed with an emphasis on circumventing depletion region recombination. PMID- 26267041 TI - Stacking fault related luminescence in GaN nanorods. AB - Optical and structural properties are presented for GaN nanorods (NRs) grown in the [0001] direction on Si(111) substrates by direct-current reactive magnetron sputter epitaxy. Transmission electron microscopy (TEM) reveals clusters of dense stacking faults (SFs) regularly distributed along the c-axis. A strong emission line at ~3.42 eV associated with the basal-plane SFs has been observed in luminescence spectra. The optical signature of SFs is stable up to room temperatures with the activation energy of ~20 meV. Temperature-dependent time resolved photoluminescence properties suggest that the recombination mechanism of the 3.42 eV emission can be understood in terms of multiple quantum wells self organized along the growth axis of NRs. PMID- 26267042 TI - Targeting tumor vasculature: expanding the potential of DNA cancer vaccines. AB - Targeting the tumor vasculature with anti-angiogenesis modalities is a bona fide validated approach that has complemented cancer treatment paradigms. Tumor vasculature antigens (TVA) can be immunologically targeted and offers multiple theoretical advantages that may enhance existing strategies against cancer. We focused on tumor endothelial marker 1 (TEM1/CD248) as a model TVA since it is broadly expressed on many different cancers. Our DNA-based vaccine approach demonstrated that CD248 can be effectively targeted immunologically; anti-tumor responses were generated in several mouse models; and CD8(+)/CD4(+) T cell responses were elicited against peptides derived from CD248 protein. Our work supports our contention that CD248 is a novel immunotherapeutic target for cancer treatment and highlights the efficient, safe and translatable use of DNA-based immunotherapy. We next briefly highlight ongoing investigations targeting CD248 with antibodies as a diagnostic imaging agent and as a therapeutic antibody in an early clinical trial. The optimal approach for generating effective DNA-based cancer vaccines for several tumor types may be a combinatorial approach that enhances immunogenicity such as combination with chemotherapy. Additional combination approaches are discussed and include those that alleviate the immunosuppressive tumor microenvironment induced by myeloid-derived suppressor cells and T regulatory cells. Targeting the tumor vasculature by CD248-based immunological modalities expands the armamentarium against cancer. PMID- 26267043 TI - Immune checkpoint targeting as anti-cancer immunotherapy: promises, questions, challenges and the need for predictive biomarkers at ASCO 2015. AB - Immunotherapy targeting "immune checkpoints" first made the headlines at the ASCO (American Society of Clinical Oncology) Annual Meeting in 2013, took centre stage at 2014 and consolidated its position as a potentially curative first-line therapy as reflected by the presentations at ASCO 2015. For the first time, previously refractory cancers are proving amenable to treatment, but still only a fraction, usually a minority, of patients respond. The hunt for factors predicting responses and for biomarkers to monitor treatment was a major theme of this year's meeting, as briefly discussed in this Editorial. PMID- 26267044 TI - Polymorphisms in SLCO1B3 and NR1I2 as genetic determinants of hematotoxicity of carboplatin and paclitaxel combination. AB - AIM: The goal of our study was to assess the impact of patients' genetic background on their sensitivity to carboplatin/paclitaxel hematotoxicity. PATIENTS & METHODS: Parameters describing sensitivity to neutropenia and to thrombocytopenia of 201 patients were extracted from a previous pharmacokinetic/pharmacodynamics analysis, in order to assess their association with 52 candidates SNPs in 18 genes. RESULTS: Carriers of a T allele of SLCO1B3 rs4149117 were 19% less sensitive to thrombocytopenia than the homozygotes for the G allele (p = 0.00279). Carriers of two copies of the ATG haplotypes of NR1I2 rs1523130, rs3814055 and rs1523127 were 19% less sensitive to thrombocytopenia than those harboring other haplotypes (p = 0.025). CONCLUSION: Our results revealed the importance of SLCO1B3 and NR1I2 in the sensitivity to carboplatin/paclitaxel thrombocytopenia. PMID- 26267045 TI - Predictors of Relapse and Dropout During a 12-Week Relapse Prevention Program for Methamphetamine Users. AB - In this research, the possible neuropsychological predictors of relapse and dropout of group cognitive behavioral therapy (CBT) for methamphetamine (MA) users were explored. Participants were 42 MA users sentenced by the judicial system to take part in an out-patient relapse prevention program for MA abuse and dependence that employs a CBT model once a week over the course of 12 weeks. Baseline neuropsychological functions were evaluated with the Conners' Continuous Performance Test, Wisconsin Card Sorting Test, Iowa Gambling Task, and Barratt Impulsiveness Scale. All participants had to submit to urine drug tests every week. Of the 42 participants, 69.0% had a MA positive urine screening result at least once throughout the program (relapse), while 40.5% dropped out of the treatment program prior to its completion. Short duration of MA abstinence at baseline and poor attention predicted relapse. Predictors of dropout included being unmarried and having risky decision making. Findings may be helpful for clinicians, who can screen for the aforementioned risk factors and provide strategies for high-risk patients to help prevent relapse and dropout among MA users in treatment programs. PMID- 26267046 TI - Two novel herbicide candidates affect Arabidopsis thaliana growth by inhibiting nitrogen and phosphate absorption. AB - Both 2-[(2,4-dichlorophenoxy)acetoxy](methy)lmethyl-5,5-dimethyl-1,3,2 dioxaphosphinan-2-one (termed as IIa) and 2-[(4-chloro-2-methyl-phenoxy) acetoxy](methyl)methyl-5,5-dimethyl-1,3,2-dioxaphosphinan-2-one (termed as IIr) are novel herbicide candidates that positively affect herbicidal activity via the introduction of a phosphorus-containing heterocyclic ring. This report investigated the mechanism of IIa and IIr on weed control in the model plant Arabidopsis thaliana at physiological, ultrastructural and molecular levels. IIa and IIr significantly inhibited the growth of A. thaliana and altered its root structure by inhibiting energy metabolism and lipid or protein biosynthesis. These compounds also significantly affected the absorption of nitrogen and phosphorus by down-regulating the transcripts of nitrate transporter-related genes, ammonium transporter-related genes and phosphorus transporter-related genes. PMID- 26267047 TI - Proteomic analysis on zoxamide-induced sensitivity changes in Phytophthora cactorum. AB - Zoxamide is an important fungicide for oomycete disease management. In this study, we established the baseline sensitivity of Phytophthora cactorum to zoxamide and assessed the risk of developing resistance to zoxamide using ultraviolet irradiation and fungicide taming methods. All 73 studied isolates were sensitive to zoxamide, with effective concentrations for 50% inhibition of mycelial growth ranging from 0.04 to 0.29 mg/L and mean of 0.15 mg/L. Stable zoxamide-resistant mutants of P. cactorum were not obtained from four arbitrarily selected isolates by either treating mycelial cultures with ultraviolet irradiation or adapting mycelial cultures to the addition of increasing zoxamide concentrations. However, the sensitivity of the isolates to zoxamide could be easily reduced by successive zoxamide treatments. In addition to displaying decreased sensitivity to zoxamide, these isolates also showed decreased sensitivity to the fungicides flumorph and cymoxanil. Proteomic analysis indicated that some proteins involved in antioxidant detoxification, ATP dependent multidrug resistance, and anti-apoptosis activity, are likely responsible for the induced decrease in the sensitivity of P. cactorum to zoxamide compared to controls. Further semi-quantitative PCR analysis demonstrated that the gene expression profiles of most of above proteins were consistent with the proteomic analysis. Based on the above results, P. cactorum shows low resistance risk to zoxamide; however, the fungicidal effect of zoxamide might be decreased due to induced resistance when this fungicide is continuously applied. PMID- 26267048 TI - Evaluation of lipid peroxidation and antioxidant status on fenvalerate, nitrate and their co-exposure in Bubalus bubalis. AB - The toxic effects of pesticides and minerals have been explored in different species, but still there is paucity of information regarding their combined toxicological effects. The present investigation reports oxidative stress induced by oral subacute exposure to fenvalerate (1 mg/kg) and sodium nitrate (20 mg/kg) alone, as well as in combination daily for 21 days in buffalo calves. Fenvalerate exposure produced significant elevation in lipid peroxidation (LPO), glutathione peroxidase (GPx), while it produced significant decline in blood glutathione (GSH) levels, superoxide dismutase (SOD) and catalase (CAT). No significant alteration was evidenced in nitric oxide (NOx) levels. Oral exposure to sodium nitrate produced significant inclination in LPO and NOx, while on the other hand significant depreciation in SOD and CAT with no significant change in GPx activity. Combined exposure to fenvalerate and sodium nitrate produced severe effects with an appreciably more prominent elevation in extent of LPO and decline in blood GSH levels. PMID- 26267049 TI - RETRACTED: Glyphosate herbicide induces genotoxic effect and physiological disturbances in Bulinus truncatus snails. AB - Herbicides are being used in agriculture for controlling noxious weed. Glyphosate is a herbicide that is widely applied to cereal crops in Egypt and is used in controlling a very broad spectrum of weeds. The present study was designed to investigate the response of the snail Bulinus truncatus as a bioindicator for physiological and molecular aspects of B. truncatus snails after exposure to sublethal concentrations of glyphosate for two weeks. In treating snails, glucose concentration (GL) in the haemolymph as well as lactate (LT) in soft tissues of treated snails increased, while glycogen (GN), pyruvate (PV), total protein (TP), nucleic acids (DNA and RNA) levels in snail's tissues decreased. The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR), thioredoxin reductase (TrxR), glycogen phosphorylase (GP), glucose-6-phosphatase (G-6-Pase), succinic dehydrogenase (SDH) and lactic dehydrogenase (LDH) enzymes in homogenate of snail's tissues were reduced in response to the treatment with the herbicide, while lipid peroxide (LP), sorbitol dehydrogenase (SDH) and transaminases (GOT and GPT) activity increased (P < 0.001). The changes in the number, position and intensity of DNA bands induced by glyphosate herbicide may be attributed to the fact that the herbicide can induce genotoxicity through DNA damage. Thus, the present result indicated that the genotoxicity products at low concentration and for long time treatment showed the hazard of herbicide addiction on man's life. PMID- 26267050 TI - Photosynthetic and antioxidative alterations in coffee leaves caused by epoxiconazole and pyraclostrobin sprays and Hemileia vastatrix infection. AB - Coffee leaf rust (CLR), caused by Hemileia vastatrix, is a major disease affecting coffee production worldwide. In this study, an in-depth analysis of the photosynthetic performance of coffee leaves challenged or not with H. vastatrix and sprayed with either epoxiconazole (EPO) or pyraclostrobin (PYR) was performed by combining chlorophyll a fluorescence images, photosynthetic pigment pools and the activities of chitinase (CHI), beta-1,3-glucanase (GLU), peroxidase (POX) and catalase (CAT). The CLR severity was higher in the control plants, but reduced in plants sprayed with both PYR and EPO. Also, the CLR severity was reduced in plants sprayed with PYR compared with plants sprayed with EPO. Plants sprayed with either EPO or PYR showed maximal photosystem II quantum efficiency (Fv/Fm) values ranging from 0.78 to 0.80, which were quite similar to those obtained with inoculated plants (values ranging from 0.74 to 0.77). The decreases in the Fv/Fm ratio values and parallel increases in the F0 values in the inoculated plants, which were not observed in the control plants (sprayed with water) and were confirmed by images of the initial fluorescence (F0) and Fv/Fm parameters in the regions of the leaf tissue containing pustules and in the asymptomatic leaf tissue, indicated that photosynthesis was negatively impacted. When effective photosystem II quantum yield (Y(II)) values approached zero with a high photosynthetic photon flux density, high values of quantum yield of regulated energy dissipation (Y(NPQ)) in association with a high carotenoid concentration were noted in the inoculated plants sprayed either with PYR or EPO. The increased CLR severity in inoculated plants in contrast to inoculated plants sprayed with either PYR or EPO was associated with greater POX activity and a reduced photosynthetic pigment concentration. POX and CAT activities were increased in inoculated plants sprayed with either EPO or PYR when compared with control plants. CHI and GLU activities were maintained at high levels in the leaves of inoculated plants, regardless of the fungicide sprayed, indicating that CHI and GLU are less important for coffee resistance against CLR. The results of the present study clearly demonstrated that plants sprayed with either EPO or PYR showed milder CLR symptoms with adequate photosynthetic performance and optimal conditioning of their antioxidant systems. PMID- 26267051 TI - ACCase mutations in Avena sterilis populations and their impact on plant fitness. AB - Avena sterilis (sterile oat) populations originating from wheat-growing regions of Greece, developed resistance to fenoxaprop, clodinafop and other herbicides. The partial ACCase gene sequence revealed six point mutations (Ile-1781-Leu, Trp 1999-Cys, Trp-2027-Cys, Ile-2041-Asn, Asp-2078-Gly, and Cys-2088-Arg) in 24 out of the 26 resistant (R) populations, confirming the molecular mechanism of resistance to ACCase-inhibiting herbicides. However, DNA sequence of two R populations did not reveal any known ACCase mutations, suggesting possible presence of unknown mutation or metabolism-based mechanism of resistance. The Cys 2088-Arg mutation is the first record for ACCase mutant conferring target-site resistance in A. sterilis worldwide. The evaluation of 12 R and 6 susceptible (S) populations under non-competitive field conditions did not indicate consistent mean growth rate differences, whereas the pot evaluation of the same (12 R and 6 S) populations grown in competition with wheat or in pure stands showed significant growth (fresh weight and panicle number) differences between six S populations and between six R populations containing the same ACCase mutation (Ile-2041-Asn). Finally, one S and five R (Trp-1999-Cys, Trp-2027-Cys, Ile-2041 Asn, Asp-2078-Gly, and Cys-2088-Arg) populations grown under field competitive conditions indicated fresh weight and panicle number differences in competition with other populations as compared with pure stands. These findings suggest clearly that the inconsistent fitness differences between R and S A. sterilis populations are not related with the ACCase resistance trait but they may result from other non-resistance fitness traits selected in their different geographical locations. PMID- 26267052 TI - Mosquito larvicidal and pupaecidal potential of prodigiosin from Serratia marcescens and understanding its mechanism of action. AB - Mosquitoes spread lethal diseases like malaria and dengue fever to humans. Considering mosquito vector control as one of the best alternatives to reduce new infections, here we have analyzed the effect of purified pigment prodigiosin extracted from Serratia marcescens (NMCC 75) against larval and pupal stages of Aedes aegypti and Anopheles stephensi mosquitoes. Mosquito larvicidal activities of purified prodigiosin revealed LC50 values of 14 +/- 1.2, 15.6 +/- 1.48, 18 +/- 1.3, 21 +/- 0.87 ug/ml against early IInd, IIIrd, IVth instar and pupal stages of Ae. aegypti, respectively. LC50 values for An. stephensi were found to be 19.7 +/ 1.12, 24.7 +/- 1.47, 26.6 +/- 1.67, 32.2 +/- 1.79 ug/ml against early IInd, IIIrd, IVth instar and pupae of An. stephensi, respectively. Further investigations toward understanding modes of action revealed variations in the activities of esterases, acetylcholine esterases, phosphatases, proteases and total proteins in the fourth instar larvae of Ae. aegypti indicating intrinsic difference in biochemical features due to prodigiosin treatment. Although there was no inhibition of enzymes like catalase and oxidase but may have profound inhibitory effect on carbonic anhydrase or H(+)-V-ATPase which is indicated by change in the pH of midgut and caeca of mosquito larvae. This reduced pH may be possibly due to the proton pump inhibitory activity of prodigiosin. Pure prodigiosin can prove to be an important molecule for mosquito control at larval and pupal stages of Ae. aegypti and An. stephensi. This is the first report on the mosquito pupaecidal activity of prodigiosin and its possible mechanism of action. PMID- 26267054 TI - Instar-dependent systemic RNA interference response in Leptinotarsa decemlineata larvae. AB - RNA interference (RNAi) is a promising approach to control Leptinotarsa decemlineata. In this study, RNAi efficiency by double-stranded RNA (dsRNA) targeting S-adenosyl-L-homocysteine hydrolase (LdSAHase) was compared among L. decemlineata first- to fourth-instar larvae. Ingesting dsLdSAHase successfully decreased the target gene expression, caused lethality, inhibited growth and impaired pupation in an instar- and concentration-dependent manner. To study the role of Dicer2 and Argonaute2 genes in RNAi efficiency, we identified LdDcr2a, LdDcr2b, LdAgo2a and LdAgo2b. Their expression levels were higher in young larvae than those in old ones. Exposure to dsegfp for 6 h significantly elevated LdDcr2a, LdDcr2b, LdAgo2a and LdAgo2b mRNA levels in the first-, second-, third- and fourth-instar larvae. When the exposure periods were extended, however, the expression levels were gradually reduced. Continuous exposure for 72 h significantly repressed the expression of LdAgo2a and LdAgo2b in the first, second and third larval instars, and the four genes in final instars. Moreover, we found that dsLdSAHase-caused LdSAHase suppressions and larval mortalities were influenced by previous dsegfp exposure: 12 h of previous exposure increased LdSAHase silencing and mortality of the final instar larvae, whereas 72 h of exposure reduced LdSAHase silencing and mortality. Thus, it seems the activities of core RNAi-machinery proteins affect RNAi efficiency in L. decemlineata. PMID- 26267053 TI - Molecular characterization of a ryanodine receptor gene from Spodoptera exigua and its upregulation by chlorantraniliprole. AB - Chlorantraniliprole is a novel diamide insecticide that targets the insect ryanodine receptor, a Ca(2+) release channel. Spodoptera exigua is a significant insect pest, and chlorantraniliprole is the most popular diamide insecticide used against this pest. To better understand the effects of diamides on RyR expression and [Ca(2+)], we isolated the SeRyR cDNA and investigated changes in SeRyR expression as a result of the application of chlorantraniliprole. The full-length cDNAs of SeRyR contain an open reading frame (ORF) of 15,357 bp with a predicted protein consisting of 5118 amino acids. SeRyR shares 77-92% identity with other insect RyR isoforms and 45-47% identity with vertebrate RyR isoforms. Furthermore, the relative expression abundances of RyR mRNA extracted from S. exigua fat body cells after 24 h of culture in 0.1, 1, 10, 100 nM, 1 uM and 100 uM of chlorantraniliprole changed 1.04-, 0.89-, 1.83-, 2.58-, 4.03- and 3.12-fold compared to blank control, respectively. The regression equation for the relative expression levels of SeRyR after 24 h as a function of the chlorantraniliprole concentration was Y = 0.6455 + 0.8188LgX, R(2) = 0.97093 for the cell line IOZCAS Spex-II. These results outline the effects of chlorantraniliprole on the expression of SeRyR and provide a basis for the discovery of a compound that may exhibit selective insect activity. PMID- 26267055 TI - NADPH oxidase mediated maneb- and paraquat-induced oxidative stress in rat polymorphs: Crosstalk with mitochondrial dysfunction. AB - Oxidative stress is a key factor in Parkinson's disease (PD) pathogenesis. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and impaired mitochondrion regulate oxidative stress-mediated maneb (MB)- and paraquat (PQ) induced Parkinsonism. However, their contribution in the MB- and PQ-induced toxicity in polymorphonuclear leukocytes (PMNs) is still elusive. The study investigated the role of NADPH oxidase and mitochondria in MB- and/or PQ-induced oxidative stress in the PMNs and the crossing point between the two. Animals were treated with MB and/or PQ for 1-3 weeks along with respective controls. In a few sets of experiments, rats were treated with/without NADPH oxidase inhibitor, apocynin, an hour prior to MB and/or PQ treatment. PMNs of MB and/or PQ treated animals were also treated with/without carbonyl cyanide 3-chlorophenylhydrazone (CCCP) to assess the role of the mitochondria in superoxide and total free radical productions. MB and/or PQ were found to increase the level of total reactive oxygen species (ROS), superoxide radicals, catalytic activity and expression of NADPH oxidase and superoxide dismutase (SOD1/2) and mitochondrial ROS content in a time dependent manner. Conversely, catalase activity and mitochondrial membrane potential were attenuated. Apocynin alleviated MB- and/or PQ-induced changes in total ROS, superoxide radicals, expression/catalytic activity of NADPH oxidase and SOD1/2 along with the mitochondrial ROS and membrane potential. CCCP also inhibited ROS and superoxide levels in the PMNs of MB and/or PQ-treated animals. The results demonstrate the involvement of NADPH oxidase and mitochondrial dysfunction in MB and PQ-induced oxidative stress in PMNs and a plausible crosstalk between them. PMID- 26267056 TI - Status of insecticide resistance and selection for imidacloprid resistance in the ladybird beetle Propylaea japonica (Thunberg). AB - Field populations or strains of Propylaea japonica collected from four places in southern China (Guangzhou, Nanning, Guilin, and Yuxi) were tested for susceptibility to four insecticides (abamectin, imidacloprid, beta-cypermethrin, and chlorpyrifos) by the Petri-dish Potter tower method and compared with an insecticide-susceptible strain. Concentrations that proved lethal for 50% of the tested individuals (LC50) were estimated by probit analysis, and resistance factors (RF) were calculated at the LC50 level, which ranged from 1.6 to 10.1, depending on the insecticide. In addition, the Guangzhou strain formed the original population for imidacloprid resistance selection. After selection for 20 generations, the resistance had increased 39.3-fold. Fitness analysis in terms of such traits as fecundity, days to maturity, and survival showed that although both resistant and susceptible populations developed at comparable rates, the resistant strain was less fecund (it laid fewer eggs and a smaller proportion of those eggs hatched and resulted in adults), attaining a fitness score of only 0.56 relative to the susceptible strain. These observations suggest that it is possible to detect strains of P. japonica highly resistant to insecticides under laboratory conditions, and that resistance to imidacloprid carries considerable fitness costs to P. japonica. The study served to expand our understanding of the impact of imidacloprid resistance on biological parameters of P. japonica in more detail and to facilitate the deployment of natural enemies resistant to insecticides in integrated pest management. PMID- 26267057 TI - An antenna-biased carboxylesterase is specifically active to plant volatiles in Spodoptera exigua. AB - Odorant-degrading enzymes (ODEs) in sensillar lymph are proposed to play important roles in the maintenance of the sensitivity of the olfactory sensilla, by timely degrading the odorants that have already fulfilled the activation of the odorant receptor (OR). Here we reported the cloning and characterization of an ODE gene (SexiCXE10) from the polyphagous insect pest Spodoptera exigua. SexiCXE10 is a carboxylesterase (CXE) gene, encoding a protein with 538 amino acid residues, and bearing typical characteristics of Carboxyl/cholinesterase (CCE, EC 3.1.1.1.) gene family. Tissue-temporal expression pattern by qPCR revealed that the SexiCXE10 mRNA was highly antenna biased, and maintained at high level throughout the adult stage. Further fluorescence in situ hybridization demonstrated that SexiCXE10 mRNA signal was detected under sensilla basiconica and short and long sensilla trichodea. Finally, enzymatic study using purified recombinant enzyme showed that SexiCXE10 had high activity specifically for ester plant volatiles with 7-10 carbon atoms, while no activity was found with S. exigua sex pheromone components and plant volatiles with more carbon atoms. In addition, SexiCXE10 displayed lower activity at acidic pH (pH 5.0), while higher activity was found at neutral and alkaline conditions (pH 6.5-9.0). Our results suggest that SexiCXE10 may play an important role in the degradation of the host plant volatiles, and thus contributes to the high sensitivity of the olfactory system in S. exigua. Meanwhile, the CXE would be a potential target for developing behavioral antagonists and pesticides against S. exigua. PMID- 26267058 TI - More than just one: multiplicity of Hirudins and Hirudin-like Factors in the Medicinal Leech, Hirudo medicinalis. AB - Blood-sucking leeches like the medicinal leech, Hirudo medicinalis, have been used for medical purposes since ancient times. During feeding, medicinal leeches transfer a broad range of bioactive substances into the host's wound to prevent premature hemostasis and blood coagulation. Hirudin is probably the best known of these substances. Despite its long history of investigation, recombinant production and clinical use, there still exist conflicting data regarding the primary structure of hirudin. Entirely unclear is the potential biological significance of three different subtypes and many isoforms of hirudins that have been characterized so far. Furthermore, there is only incomplete information on their cDNA sequences and no information at all on gene structures and DNA sequences are available in the databases. Our efforts to fill these gaps revealed the presence of multiple hirudin-encoding genes in the genome of Hirudo medicinalis. We have strong evidence for the expression of all three subtypes of hirudin within individual leeches and for the expression of additional hirudins or hirudin-like factors that may have different biological functions and may be promising candidates for new drugs. PMID- 26267059 TI - Altered Mucin and Glycoprotein Expression in Dry Eye Disease. AB - PURPOSE: Mucins are among the many important constituents of a healthy tear film. Mucins secreted and/or associated with conjunctival goblet cells, ocular mucosal epithelial cells, and the lacrimal gland must work together to create a stable tear film. Although many studies have explored the mechanism(s) whereby mucins maintain and protect the ocular surface, the effects of dry eye on the structure and function of ocular mucins are unclear. Here, we summarize current findings regarding ocular mucins and how they are altered in dry eye. METHODS: We performed a literature review of studies exploring the expression of mucins produced and/or associated with tissues that comprise the lacrimal functional unit and how they are altered in dry eye. We also summarize new insights on the immune-mediated effects of aqueous tear deficiency on ocular surface mucins that we discovered using a mouse model of dry eye. RESULTS: Although consistent decreases in MUC5AC and altered expression of membrane-bound mucins have been noted in both Sjogren and non-Sjogren dry eye, many reports of altered mucins in dry eye are contradictory. Mechanistic studies, including our own, suggest that changes in the glycosylation of mucins rather than the proteins themselves may occur as the direct result of local inflammation induced by proinflammatory mediators, such as interleukin-1. CONCLUSIONS: Altered expression of ocular mucins in dry eye varies considerably from study to study, likely attributed to inherent difficulties in analyzing small-volume tear samples, as well as differences in tear collection methods and disease severity in dry eye cohorts. To better define the functional role of ocular mucin glycosylation in the pathogenesis of dry eye disease, we propose genomic and proteomic studies along with biological pathway analysis to reveal novel avenues for exploration. PMID- 26267060 TI - Longitudinal Evaluation of Visual Function in Multiple Sclerosis. AB - PURPOSE: To evaluate longitudinal changes of visual function in relapsing remitting multiple sclerosis (RRMS). METHODS: Multifocal visual evoked potential (mfVEP), contrast sensitivity (CS), and Humphrey visual fields (HVFs) were obtained at two visits (mean follow-up, 1.5 [+/-0.9] years) in both eyes of 57 RRMS patients (53 eyes with optic neuritis [ON]: 14 ON within 6 months of first visit [ON < 6 months] and 39 ON >= 6 months; 57 non-ON). Longitudinal changes were assessed using mfVEP amplitude (log signal-to-noise ratio [logSNR]), latency, CS, and HVF mean deviation based on established 95% tolerance limits of test-retest variability. RESULTS: A significant percentage of eyes in the ON < 6 months group exceeded 95% tolerance limits for mfVEP logSNR (21%, p < 0.05), latency (35%, p < 0.01), and CS (31% p < 0.001); more improved than worsened over time (14% vs. 7% for logSNR, 21% vs. 14% for latency, and 31% vs. 0% for CS). Multifocal visual evoked potential latency decreased in 11% of non-ON eyes and in 10% of eyes in the ON >= 6 months group, and increased in 21% and 10%, respectively (p < 0.01 for all). Latency changes correlated negatively with baseline latency (r = -0.43 and -0.45 for non-ON and ON >= 6 months; p = 0.0008). Although a nonsignificant percentage of non-ON and ON >= 6 months eyes exceeded tolerance limits for logSNR, CS, or HVF, logSNR and latency changes correlated, and both measures correlated with changes in CS (r = 0.47 to 0.79, p < 0.01). CONCLUSIONS: Multifocal visual evoked potential, particularly latency, is potentially useful for assessing neuroprotective and remyelinating strategies in RRMS. PMID- 26267061 TI - The development of bioactive peptides from dietary proteins as a dipeptidyl peptidase IV inhibitor for the management of type 2 diabetes. AB - One of the new approaches to the management of type 2 diabetes mellitus (T2DM) consists of orally administered dipeptidyl peptidase-IV (DPP-IV) inhibitors. These synthetic drug inhibitors are reported to have some side effects and that subsequently limits their applications. There is a growing interest to develop natural DPP-IV inhibitors that will be potent without undesirable side effects. Many in vitro and some in vivo studies have highlighted the potential of food derived peptides functioning as effective DPPIV inhibitors. Bioactive peptides within original food-derived proteins are inactive but can be activated by being released during food processing (by enzymatic hydrolysis or fermentation) or during gastrointestinal digestion. Hence, the utilization of computer-aided techniques as screening tools may be helpful in predicting the potential of food proteins as precursors of DPP-IV inhibitory peptides. This paper reviews the current literature on DPP-IV inhibitory peptides, focusing on their in vitro activity and in vivo antidiabetic effects. In addition, the feasibility of various in silico approaches is also summarized in this review. PMID- 26267062 TI - Postpartum depression among visible and invisible sexual minority women: a pilot study. AB - PURPOSE: Significant numbers of sexual minority women are choosing to parent. Despite this, there is limited research on postpartum depression (PPD) with sexual minority mothers and less research considering differences within sexual minority women in the experience of PPD. This research examines two questions to address this gap in research: (1) Do experiences of PPD symptoms vary between different subgroups of sexual minority women, and (2) Which recruitment strategies effectively address the challenge of recruiting sexual minority women who are pregnant? METHODS: Two Canadian studies recruited participants via consecutive or convenience sampling from midwifery clinics and hospital sites. Participants completed prenatal and postnatal measures of PPD symptoms, social support, and perceived discrimination. RESULTS: Considering our first question, we found an interaction effect between past sexual behavior and current partner gender. Women currently partnered with men reported higher scores on the Edinburgh Postpartum Depression Scale when their sexual history included partners of more than one gender, whereas this effect was not found among women who were currently partnered with women or not partnered. Regarding our second question, most sexual minority participants recruited through convenience sampling were partnered with women and identified as lesbian or queer, while most participants recruited through consecutive sampling were partnered with men and identified as bisexual. CONCLUSIONS: Women whose sexual histories include more than one gender and are currently partnered with men may be at a higher risk for PPD symptoms. Recruitment method may influence the type of sample recruited for perinatal mental health research among sexual minority women. PMID- 26267063 TI - Anonymous birth law saves babies--optimization, sustainability and public awareness. AB - The aims of this study are to assess the impact of Austria's anonymous birth law from the time relevant statistical records are available and to evaluate the use of hatches versus anonymous hospital delivery. This study is a complete census of police-reported neonaticides (1975-2012) as well as anonymous births including baby hatches in Austria during 2002-2012. The time trends of neonaticide rates, anonymous births and baby hatches were analysed by means of Poisson and logistic regression model. Predicted and observed rates were derived and compared using a Bayesian Poisson regression model. Predicted numbers of neonaticides for the period of the active awareness campaign, 2002-2004, were more than three times larger than the observed number (p = 0.0067). Of the 365 women who benefitted from this legislation, only 11.5% chose to put their babies in a baby hatch. Since the law was introduced, a significant decreasing tendency of numbers of anonymous births (p = 047) was observed, while there was significant increase of neonaticide rates (p = 0.0001). The implementation of the anonymous delivery law is associated with a decrease in the number of police-reported neonaticides. The subsequent significantly decreasing numbers of anonymous births with an accompanying increase of neonaticides represents additional evidence for the effectiveness of the measure. PMID- 26267064 TI - Quercetin Protects Mice from ConA-Induced Hepatitis by Inhibiting HMGB1-TLR Expression and Down-Regulating the Nuclear Factor Kappa B Pathway. AB - The dietary flavonoid quercetin has hepatoprotective effects. We analyzed the effects of quercetin on concanavalin A (ConA)-induced hepatitis in mice and its underlying molecular mechanisms of action. Mice were administered quercetin (50 mg/kg body weight, i.p.) or vehicle 30 min before intravenous administration of ConA. Quercetin pretreatment significantly reduced the ConA-induced elevations in plasma aminotransferase concentrations and liver necrosis, as well as reducing serum concentrations of the pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interferon-gamma, and interleukin-4. Quercetin pretreatment also reduced expression of high-mobility group box 1 protein (HMGB1) and toll-like receptor (TLR)-2 and TLR-4 messenger RNA (mRNA) and protein in liver tissues. Quercetin pretreatment significantly inhibited degradation of inhibitory kappa B alpha and modulated ConA-induced nuclear translocation in the liver of nuclear factor kappa B (NF-kappaB) p65. These results demonstrate that quercetin protects against ConA-mediated hepatitis in mice by attenuating the HMGB1-TLRs-NF-kappaB signaling pathway. PMID- 26267066 TI - Simulated heat waves affected alpine grassland only in combination with drought. AB - The Alpine region is warming fast, and concurrently, the frequency and intensity of climate extremes are increasing. It is currently unclear whether alpine ecosystems are sensitive or resistant to such extremes. We subjected Swiss alpine grassland communities to heat waves with varying intensity by transplanting monoliths to four different elevations (2440-660 m above sea level) for 17 d. Half of these were regularly irrigated while the other half were deprived of irrigation to additionally induce a drought at each site. Heat waves had no significant impacts on fluorescence (Fv /Fm , a stress indicator), senescence and aboveground productivity if irrigation was provided. However, when heat waves coincided with drought, the plants showed clear signs of stress, resulting in vegetation browning and reduced phytomass production. This likely resulted from direct drought effects, but also, as measurements of stomatal conductance and canopy temperatures suggest, from increased high-temperature stress as water scarcity decreased heat mitigation through transpiration. The immediate responses to heat waves (with or without droughts) recorded in these alpine grasslands were similar to those observed in the more extensively studied grasslands from temperate climates. Responses following climate extremes may differ in alpine environments, however, because the short growing season likely constrains recovery. PMID- 26267065 TI - The Metabolome in Finnish Carriers of the MYBPC3-Q1061X Mutation for Hypertrophic Cardiomyopathy. AB - AIMS: Mutations in the cardiac myosin-binding protein C gene (MYBPC3) are the most common genetic cause of hypertrophic cardiomyopathy (HCM) worldwide. The molecular mechanisms leading to HCM are poorly understood. We investigated the metabolic profiles of mutation carriers with the HCM-causing MYBPC3-Q1061X mutation with and without left ventricular hypertrophy (LVH) and non-affected relatives, and the association of the metabolome to the echocardiographic parameters. METHODS AND RESULTS: 34 hypertrophic subjects carrying the MYBPC3 Q1061X mutation, 19 non-hypertrophic mutation carriers and 20 relatives with neither mutation nor hypertrophy were examined using comprehensive echocardiography. Plasma was analyzed for molecular lipids and polar metabolites using two metabolomics platforms. Concentrations of branched chain amino acids, triglycerides and ether phospholipids were increased in mutation carriers with hypertrophy as compared to controls and non-hypertrophic mutation carriers, and correlated with echocardiographic LVH and signs of diastolic and systolic dysfunction in subjects with the MYBPC3-Q1061X mutation. CONCLUSIONS: Our study implicates the potential role of branched chain amino acids, triglycerides and ether phospholipids in HCM, as well as suggests an association of these metabolites with remodeling and dysfunction of the left ventricle. PMID- 26267067 TI - The Pathogenic Role of Low Range Repeats in SCA17. AB - INTRODUCTION: SCA17 is an autosomal dominant cerebellar ataxia with expansion of the CAG/CAA trinucleotide repeats in the TATA-binding protein (TBP) gene. SCA17 can have various clinical presentations including parkinsonism, ataxia, chorea and dystonia. SCA17 is diagnosed by detecting the expanded CAG repeats in the TBP gene; however, in the literature, pathologic repeat numbers as low as 41 overlap with normal repeat numbers. METHODS: The subjects in this study included patients with involuntary movement disorders such as cerebellar ataxia, parkinsonism, chorea and dystonia who visited Seoul National University Hospital between Jan. 2006 and Apr. 2014 and were screened for SCA17. Those who were diagnosed with other genetic diseases or nondegenerative diseases were excluded. DNA from healthy subjects who did not have a family history of parkinsonism, ataxia, psychiatric symptoms, chorea or dystonia served as the control. In total, 5242 chromosomes from 2099 patients and 522 normal controls were analyzed. RESULTS: The total number of patients included in the analysis was 2099 (parkinsonism, 1706; ataxia, 345; chorea, 37; and dystonia, 11). In the normal control, up to 44 repeats were found. In the 44 repeat group, there were 7 (0.3%) patients and 1 (0.2%) normal control. In 43 repeat group, there were 8 (0.4%) patients and 2 (0.4%) normal controls. In the 42 repeat group, there were 16 (0.8%) patients and 3 (0.6%) normal controls. In 41 repeat group, there were 48 (2.3%) patients and 8 (1.5%) normal controls. Considering the overlaps and non-significant differences in allelic frequencies between the patients and the normal controls with low expansions, we could not determine a definitive cutoff value for the pathologic CAG repeat number of SCA17. CONCLUSION: Because the statistical analysis between the normal controls and patients with low range expansions failed to show any differences so far, we must consider that clinical cases with low range expansions could be idiopathic movement disorders showing coincidental CAG/CAA expansions. Thus, we need to reconsider the pathologic role of low range expansions (41-42). Long term follow up and comprehensive investigations using autopsy and imaging studies in patients and controls with low range expansions are necessary to determine the cutoff value for the pathologic CAG repeat number of SCA17. PMID- 26267068 TI - Automatic tissue segmentation of head and neck MR images for hyperthermia treatment planning. AB - A hyperthermia treatment requires accurate, patient-specific treatment planning. This planning is based on 3D anatomical models which are generally derived from computed tomography. Because of its superior soft tissue contrast, magnetic resonance imaging (MRI) information can be introduced to improve the quality of these 3D patient models and therefore the treatment planning itself. Thus, we present here an automatic atlas-based segmentation algorithm for MR images of the head and neck. Our method combines multiatlas local weighting fusion with intensity modelling. The accuracy of the method was evaluated using a leave-one out cross validation experiment over a set of 11 patients for which manual delineation were available. The accuracy of the proposed method was high both in terms of the Dice similarity coefficient (DSC) and the 95th percentile Hausdorff surface distance (HSD) with median DSC higher than 0.8 for all tissues except sclera. For all tissues, except the spine tissues, the accuracy was approaching the interobserver agreement/variability both in terms of DSC and HSD. The positive effect of adding the intensity modelling to the multiatlas fusion decreased when a more accurate atlas fusion method was used.Using the proposed approach we improved the performance of the approach previously presented for H&N hyperthermia treatment planning, making the method suitable for clinical application. PMID- 26267069 TI - Altered Fronto-Temporal Functional Connectivity in Individuals at Ultra-High-Risk of Developing Psychosis. AB - BACKGROUND: The superior temporal gyrus (STG) is one of the key regions implicated in psychosis, given that abnormalities in this region are associated with an increased risk of conversion from an at-risk mental state to psychosis. However, inconsistent results regarding the functional connectivity strength of the STG have been reported, and the regional heterogeneous characteristics of the STG should be considered. METHODS: To investigate the distinctive functional connection of each subregion in the STG, we parcellated the STG of each hemisphere into three regions: the planum temporale, Heschl's gyrus, and planum polare. Resting-state functional magnetic resonance imaging was obtained from 22 first-episode psychosis (FEP) patients, 41 individuals at ultra-high-risk for psychosis (UHR), and 47 demographically matched healthy controls. RESULTS: Significant group differences (in seed-based connectivity) were demonstrated in the left planum temporale and from both the right and left Heschl's gyrus seeds. From the left planum temporale seed, the FEP and UHR groups exhibited increased connectivity to the bilateral dorsolateral prefrontal cortex. In contrast, the FEP and UHR groups demonstrated decreased connectivity from the bilateral Heschl's gyrus seeds to the dorsal anterior cingulate cortex. The enhanced connectivity between the left planum temporale and right dorsolateral prefrontal cortex was positively correlated with positive symptom severity in individuals at UHR (r = .34, p = .03). CONCLUSIONS: These findings corroborate the fronto temporal connectivity disruption hypothesis in schizophrenia by providing evidence supporting the altered fronto-temporal intrinsic functional connection at earlier stages of psychosis. Our data indicate that subregion-specific aberrant fronto-temporal interactions exist in the STG at the early stage of psychosis, thus suggesting that these aberrancies are the neural underpinning of proneness to psychosis. PMID- 26267070 TI - Spalt-like transcription factor 4 immunopositivity is associated with epithelial cell adhesion molecule expression in combined hepatocellular carcinoma and cholangiocarcinoma. AB - AIM: Combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) (cHCC CC) is a rare biphasic liver cancer. Recent studies have demonstrated that cHCC CC originates from hepatic progenitor cells (HPCs). Spalt-like transcription factor 4 (SALL4) is a marker for a progenitor subclass of HCC with an aggressive phenotype. However, little has been revealed about SALL4 expression in cHCC-CC. The aims of this study were to report SALL4 immunopositivity and the results of clinicopathological analysis in cHCC-CC, and to examine the two different nuclear immunostaining patterns for SALL4. METHODS AND RESULTS: We defined the diffuse finely granular nuclear immunostaining pattern as immunopositive for SALL4; this was observed in eight (8.9%) of 90 cHCC-CCs. SALL4 immunopositivity was significantly associated with immunopositivity for alpha-fetoprotein, glypican 3, and epithelial cell adhesion molecule (EpCAM). There was no relationship between SALL4 immunopositivity and prognosis. We confirmed SALL4 mRNA expression in samples with a punctuate/clumped immunostaining pattern, which showed a significantly lower rate of immunopositivity for EpCAM than those with a diffuse finely granular pattern. CONCLUSIONS: SALL4 immunopositivity is not a prognostic factor in cHCC-CC; however, it is associated with alpha-fetoprotein, glypican 3 and EpCAM immunopositivity, indicating the mechanism of carcinogenesis. Further study is necessary to interpret the immunostaining pattern for SALL4. PMID- 26267072 TI - A system-wide approach from the community to the hospital for improving neurologic outcomes in out-of-hospital cardiac arrest patients. AB - OBJECTIVE: In the present study, we aimed to determine the effects of a system wide approach from the community to the hospital in improving the neurologic outcomes in out-of-hospital cardiac arrest (OHCA) patients within Sungbuk in Korea. METHODS: This study used a before-after design. In 2011, compression-only cardiopulmonary resuscitation (CPR) for citizens, a state-wide standard dispatcher assisted-CPR protocol, medical control for regional emergency medical service (EMS), provision of high-quality advanced cardiac life support (ACLS) with capnography and extracorporeal CPR, and the standard postcardiac arrest care protocol were implemented in the system-wide CPR program. CPR provision and outcomes were compared between the 2009-2010 and the 2012-2013 periods. A multivariate logistic regression model for good outcome of OHCA was used to identify interventions with a significant impact. RESULTS: In total, 581 adult nontraumatic OHCA patients who received resuscitation attempts from 2009 to 2013 were selected for the analysis of CPR provision and outcomes. CPR provision improved significantly, as indicated by the following results from 2009-2010 to 2012-2013: from 15.9 to 50.4% for bystander CPR (P<0.001), 6.0 to 0% for the proportion of no documented arrest rhythm by EMS (P=0.004), 41.4 to 62.2% for ACLS with capnography (P=0.008), 1.4 to 10.5% for extracorporeal CPR (P=0.052), 3.7 to 34.4% for successful therapeutic hypothermia in coma patients (P<0.001), and 61.5 to 87.1% for immediate coronary angiography for presumed cardiac etiology (P=0.005). Moreover, the proportion of OHCA patients who received early EMS activation, bystander CPR, appropriate attempt of defibrillation at the prehospital level, high-quality ACLS, and standard postcardiac arrest care increased from 0.5% in 2009-2010 to 8.5% in 2012-2013 (P<0.001). The rates of discharge with a good neurologic outcome improved from 3.3% in 2009-2010 to 8.5% in 2012-2013 (P<0.001). CONCLUSION: The system-wide CPR program was associated with enhancements in CPR performance at both the prehospital and the hospital level, and yielded improved neurologic outcomes in OHCA patients in a small region. PMID- 26267071 TI - A Pilot Study on Clinical and Neuroimaging Characteristics of Chinese Posterior Cortical Atrophy: Comparison with Typical Alzheimer's Disease. AB - Posterior cortical atrophy (PCA) is a clinicoradiologic neurodegenerative syndrome characterized by predominant impairment of higher visual functions. Neuroimaging and neuropathological studies show that PCA is probably an atypical presentation of Alzheimer's disease. However, in China PCA has rarely been studied and remains largely unknown. Our study therefore aimed to analyze the clinical manifestations and patterns of cerebral atrophy, amyloid beta deposition and regional glucose metabolism in Chinese PCA patients, comparing them directly with those of typical Alzheimer's disease (TAD). Seven PCA patients, 6 TAD patients and 5 controls underwent neuropsychological assessment, MRI scan, 11C PIB PET scan and 18F-FDG PET scan. Cerebral atrophy including ventricular enlargement, posterior atrophy and medial temporal lobe atrophy were evaluated with MRI. The uptake of 11C-PIB was quantified at the voxel level using the standardized uptake value ratio. Comparisons of regional cerebral glucose metabolism were calculated with statistical parametric mapping. PCA patients showed significant impairment on visuospatial function in neuropsychological assessment. And PCA patients showed more severe posterior atrophy and less severe left medial temporal lobe atrophy compared with TAD patients. The data from 11C PIB PET scanning showed that amyloid beta deposition in PCA was comparable to TAD. Moreover, in PCA the results from 18F-FDG PET scanning revealed significant hypometabolism in the temporoparietooccipital region and identified specific hypometabolism in the right occipital lobe, compared with TAD. Our study thus provides a preliminary view of PCA in Chinese patients. A further study with a larger number of subjects would be recommended to confirm these findings. PMID- 26267073 TI - Associations between perceived discrimination and health status among frequent Emergency Department users. AB - OBJECTIVE: Frequent Emergency Department (ED) users are vulnerable individuals and discrimination is usually associated with increased vulnerability. The aim of this study was to investigate frequent ED users' perceptions of discrimination and to test whether they were associated with increased vulnerability. METHODS: In total, 250 adult frequent ED users were interviewed in Lausanne University Hospital. From a previously published questionnaire, we assessed 15 dichotomous sources of perceived discrimination. Vulnerability was assessed using health status: objective health status (evaluation by a healthcare practitioner including somatic, mental health, behavioral, and social issues - dichotomous variables) and subjective health status [self-evaluation including health-related quality of life (WHOQOL) and quality of life (EUROQOL) - mean-scores]. We computed the prevalence rates of perceived discrimination and tested associations between perceived discrimination and health status (Fischer's exact tests, Mann Whitney U-tests). RESULTS: A total of 35.2% of the frequent ED users surveyed reported at least one source of perceived discrimination. Objective health status was not significantly related to perceived discrimination. In contrast, experiencing perceived discrimination was associated with worse subjective health status (P<0.001). CONCLUSION: Frequent ED users are highly likely to report perceived discrimination during ED use, and this was linked to a decrease in their own rating of their health. Hence, discrimination should be taken into account when providing care to such users as it may constitute an additional risk factor for this vulnerable population. Perceived discrimination may also be of concern to professionals seeking to improve practices and provide optimal care to frequent ED users. PMID- 26267074 TI - Effects of a media campaign on resuscitation performance of bystanders: a manikin study. AB - OBJECTIVE: Cardiac arrest is associated with a poor outcome if cardiopulmonary resuscitation (CPR) is delayed. Nevertheless, CPR performance by laypersons in witnessed cardiac arrest is frequently poor. The present study evaluated the effect of a media campaign on CPR performance. PARTICIPANTS AND METHODS: CPR performance of 1000 individuals who did not have any medical background was evaluated using a resuscitation manikin. The media campaign consisted of flyers, posters, and electronic advertisement. Five hundred individuals were evaluated before the media campaign and 500 individuals after the media campaign. Age and male/female ratio were comparable within each of the groups. Premedia campaign performance was compared with postmedia campaign performance with respect to chest compressions and ventilation metrics. RESULTS: Chest compression depth and total compression work were significantly higher after the media campaign: median depth 51 mm postcampaign versus 45 mm precampaign (P<0.001), median cumulative compression work postcampaign 4176 versus 2462 mm precampaign (P<0.001). Tidal volumes and ventilation work were significantly lower following the media campaign, but did not differ between participants who had acknowledged exposure to the campaign and those who did not. Ventilation performance was generally poor across the two groups both before and after the media campaign. CONCLUSION: A simple and cost-efficient media campaign appears to enhance the performance of chest compressions. Ventilation performance and the rate of CPR performance were not increased by the campaign. PMID- 26267075 TI - Testicular torsion and the acute scrotum: current emergency management. AB - The acute scrotum is a challenging condition for the treating emergency physician requiring consideration of a number of possible diagnoses including testicular torsion. Prompt recognition of torsion and exclusion of other causes may lead to organ salvage, avoiding the devastating functional and psychological issues of testicular loss and minimizing unnecessary exploratory surgeries. This review aims to familiarize the reader with the latest management strategies for the acute scrotum, discusses key points in diagnosis and management and evaluates the strengths and drawbacks of history and clinical examination from an emergency perspective. It outlines the types and mechanisms of testicular torsion, and examines the current and possible future roles of labwork and radiological imaging in diagnosis. Emergency departments should be wary of younger males presenting with the acute scrotum. PMID- 26267076 TI - Opportunities and barriers to cardiopulmonary resuscitation training in English secondary schools. AB - OBJECTIVES: Cardiopulmonary resuscitation rates and survival from out-of-hospital cardiac arrest are poor in the UK compared with areas abroad that deliver mandatory training to all school children. We sought to identify barriers to training and develop a strategy to enable delivery of this training. METHODS: Qualitative analysis, comprising semistructured interviews and group discussions, covering 14 schools in the metropolitan borough of Calderdale in West Yorkshire. RESULTS: Only three schools out of 14 were delivering training to entire year groups. Barriers include lack of resources, lack of training for teachers and difficulty in initiating a programme. Strategies were developed to overcome these barriers with the result that four additional schools are now teaching a whole year group. There is no single solution and bespoke plans may be needed for each school. CONCLUSION: The establishment of cardiopulmonary resuscitation training in secondary schools in the UK is achievable. The commonly perceived barriers to establishment of training are all surmountable, but solving them does not necessarily ensure universal coverage. Support from healthcare professionals, in particular public health, is essential to ensure that the training is as widespread as possible. Mandatory inclusion of this training on the school curriculum, as seen in other countries, would result in significantly improved survival rates from out-of-hospital cardiorespiratory arrest. Solutions to improve training have been proposed, which could be used in other parts of Europe where such training is not a mandatory requirement. PMID- 26267077 TI - Juvenile osteochondritis dissecans of the talus: predictors of conservative treatment failure. AB - BACKGROUND: The ideal treatment for juvenile osteochondritis dissecans of the talus (ODT) is still unclear. To determine predictors of failure of conservative treatment, children admitted for ODT were retrospectively analyzed. METHODS: Patient files were analyzed to search for children treated for an ODT between 2000 and 2011. X-rays and MRI at baseline were evaluated for grading of lesions and the patient history was obtained. Final follow-up evaluation was performed via questionnaire and complementary telephone interview. Outcome was measured using the AOFAS and the Olerud/Molander scores. Conservative treatment consisted of out of sports and modification of activity under full weight-bearing. In case of persisting pain, full load removal on crutches was initiated. For further analysis, two groups were formed: (1) successful conservative treatment; (2) converted to surgical therapy. A logistic regression was used to determine potential predictors of conservative treatment failure. RESULTS: Seventy-seven lesions in 67 children with a mean age of 11.4 years (range 4-15 years) at the time of diagnosis were identified. Every patient received conservative treatment as a first-line treatment after diagnosis of ODT except for one single patient with a grade IV lesion at time of diagnosis who received operative treatment directly after diagnosis. Sixty-one percent of the lesions failed conservative treatment. A higher age as well as a grade III lesion at time of diagnosis was predictive for failure of the conservative treatment (p = 0.03 and p = 0.02, respectively). Regarding the functional outcome, a higher grade lesion in general was predictive for an inferior outcome as measured by clinical score. CONCLUSION: Grade III ODT especially in older children leads significantly more often to treatment failure when treated non-surgically. No other predictors for treatment failure could be identified. LEVEL OF EVIDENCE: Level III (retrospective comparative study). PMID- 26267078 TI - Chemotherapy-induced neutropenia and febrile neutropenia in patients with gynecologic malignancy. AB - Chemotherapy-induced neutropenia is a common complication in cancer treatment. In this study, we investigated chemotherapy-induced neutropenia that was recently detected in all patients with gynecologic malignancy. Between January 2009 and December 2011, we examined cases of chemotherapy-induced neutropenia reported in our hospital. We analyzed the incidence and clinical features of chemotherapy induced neutropenia and febrile neutropenia in patients with gynecologic malignancy. During the study period, we administered over 1614 infusions (29 regimens) to 291 patients. The median age of the patients was 60 years (range 24 84 years). Chemotherapy-induced neutropenia occurred in 147 (50.5%) patients over 378 (23.4%) chemotherapy cycles. Febrile neutropenia occurred in 20 (6.9%) patients over 25 (1.5%) cycles. The mean duration of neutropenia and fever was 3.6 days (range 1-12 days) and 3.4 days (range 1-9 days), respectively. The source of fever was unexplained by examination or cultures in 14 (56.0%) cycles. There were two cases of neutropenia-related death. Chemotherapy-induced neutropenia was associated with older age (over 70 years) (P<0.0001), less than five previous chemotherapy cycles (P=0.02), disseminated disease (P=0.03), platinum-based regimens (P<0.0001), taxane-containing regimens (P<0.0001), and combined therapy (P<0.0001). Febrile neutropenia was associated with poor performance status (P<0.0001), no previous chemotherapy (P<0.05), disseminated disease (P<0.0001), and distant metastatic disease (P=0.03). Neither chemotherapy induced neutropenia nor febrile neutropenia was associated with bone marrow metastases or previous radiotherapy. By identifying risk factors for febrile neutropenia, such as performance status, no previous chemotherapy, disseminated disease, and distant metastatic disease, the safe management of chemotherapy induced neutropenia may be possible in patients with gynecologic malignancy. PMID- 26267079 TI - Endonasal identification of the orbital apex. AB - OBJECTIVES/HYPOTHESIS: To describe anatomical landmarks for endoscopic endonasal approaches to the orbital apex and to measure the distances between those landmarks. METHODS: In this anatomic study, the nasal fossae of 30 adult fresh cadavers were dissected (n = 60 half-skulls). One double-injected orbit was carefully dissected, mainly focusing on the neurovascular structures. The orbital apex was dissected under endoscopic endonasal visualization in all cases. The distances between the ethmoidal crest and choanal arch to the optic canal (OC) and superior orbital fissure (SOF) were measured and recorded. RESULTS: The sample was predominantly male (63.3%, 19/30 cadavers). The following correlations between measurements according to side were observed: ethmoidal crest to OC, r = 0.748 (P = 0.0001); ethmoidal crest to SOF, r = 0.785 (P = 0.0001); choanal arch to OC, r = 0.835 (P = 0.0001); choanal arch to SOF, r = 0.820 (P = 0.0001). CONCLUSIONS: In the cadavers studied in this sample, the ethmoidal crest and choanal arch were relevant structures and exhibited consistent measurements. Spearman correlation coefficients were greater than 0.7, which is indicative of good correlation between measurements obtained in the skull halves of each cadaver. Comparison of the measurements obtained in different sides showed similar values, with no statistically significant differences in the distances between any of the proposed anatomic landmarks. PMID- 26267080 TI - Results of hepatic and renal function tests to different CO2 pneumoperitoneum conditions: An experimental capnoperitoneum study in dogs. AB - Carbon dioxide (CO2) is the most commonly used insufflation gas to provide exposure in the abdominal cavity during laparoscopic surgery. This study investigated the results of hepatic and renal function tests after different capnoperitoneum intraabdominal pressures in dogs. Twenty-four beagle dogs (12 males and 12 females) were used (n = 6 dogs). The intraabdominal pressure was maintained for 60 minutes, and urinalysis, hepatic and renal function tests were carried out at designed times. No surgery was performed on any of the dogs during the capnoperitoneum. In this study, whether low or high pressure, significant increases of gamma-glutamyltransferase, alkaline phosphatase, aspartate aminotransferase and creatinine levels were observed after pneumoperitoneum. However, our results showed a trend toward higher serum concentrations of some enzymes in dogs at an insufflation pressure of 15 mmHg compared to that of the other groups, although these differences did not reach statistical significance. Therefore, low pressure capnoperitoneum should be considered for dogs with compromised splanchnic function, particularly those undergoing prolonged laparoscopic surgery. PMID- 26267081 TI - Expression of inflammation-associated genes in circulating leukocytes and activity of indoleamine-2,3-dioxygenase in dairy cattle with acute puerperal metritis and bacteremia. AB - OBJECTIVE: To investigate whether expression of genes associated with inflammation and activity of indoleamine-2,3-dioxygenase (IDO) correlated with disease status and prevalence of bacteremia in post-partum dairy cattle with and without acute puerperal metritis (APM). PROCEDURES: Blood was collected from cattle with APM and control cattle matched by parity and days in milk. Leukocytes were isolated and expression of 6 genes was quantified. Activity of IDO was measured in serum with higher performance liquid chromatography (HPLC). RESULTS: The relative expression of IL-1beta in cattle with APM was significantly lower than that in controls. IDO activity was not significantly different between bacteremic and non-bacteremic cattle CONCLUSIONS AND CLINICAL RELEVANCE: The expression of IL-1beta was lower in cattle with APM. The lower levels of IL-1beta expression in PBMCs of cattle with APM suggest impaired inflammatory responses and may contribute to the development of the disease in this population of animals. PMID- 26267082 TI - Evaluation of mean echogenicity of tendons and ligaments of the metacarpal region in neonatal foals: A preliminary study. AB - The aims of this research were to evaluate mean echogenicity (ME) of the deep and superficial digital flexor tendons (DDFT and SDFT), the interosseous muscle (IM), and the accessory ligament of the deep digital flexor tendon (ALDDFT) of the metacarpal region in neonatal foals, and determine the effect of sex, side and body weight on this quantitative ultrasonographic evaluation. Thirteen orthopedically sound neonatal foals were examined. Four areas of study (1A, 1B, 2A, 2B) were identified. Transverse scans of the DDFT, SDFT, IM and ALDDFT were obtained, recorded, and analyzed. The most echogenic structures were the ALDDFT and DDFT, while the SDFT was significantly less echogenic than all other structures (P<0.05). No influence of sex, forelimb, or body weight was observed. The echogenicity of the tenodesmic structures of foals partially overlapped that reported in the metacarpal region in adult horses, except for IM. PMID- 26267083 TI - Systemic leukopenia, evaluation of laminar leukocyte infiltration and laminar lesions in horses with naturally occurring colic syndrome. AB - The present study was aimed at identifying laminar lesions and leukocyte infiltration in hoof laminar tissue of horses with colic syndrome and its correlation with the total leukocyte count before death. Six healthy horses were used as control group (CG), and eighteen horses with lethal gastrointestinal disease were divided into two groups: leukopenic group (LG) with seven leukopenic horses, and non-leukopenic group (NLG) with 11 horses with total leukocyte count within reference range for the species. Leukocyte infiltration was examined by immunohistochemistry. Laminar lesions were observed in both LG and NLG, with no differences in severity between them. LG showed increase of the leukocyte infiltration in the hoof laminar tissue, when compared to CG and NLG. Horses with severe colic syndrome (LG and NLG) developed intense laminar lesions without clinical signs of laminitis, with increased leukocyte infiltration. However, the LG demonstrated an even higher increase of leukocyte infiltration compared to both CG and NLG. PMID- 26267084 TI - Concomitance and interactions of pathogens in the Iberian wolf (Canis lupus). AB - With the aim of improving our understanding of their epidemiological features, exposure to or presence of Canine Parvovirus (CPV), Canine Distemper Virus (CDV), Leishmania infantum and Sarcoptes scabiei were studied in 88 wild wolves from Asturias (Northern Spain) by means of long-term (2004-2010) serological and molecular data. Individual and population factors and the possible interactions between them were also statistically analyzed for better understanding the contact/presence of studied pathogens. The overall seroprevalence values were 19%, 61%, 20% and 0% for CDV, CPV, S. scabiei and Leishmania, respectively, while a 46% of studied wolves showed Leishmania genetic material presence. Sarcoptic mange, CDV and CPV showed higher seroprevalence values in the areas with higher wolf densities, and a positive association between CDV and S. scabiei antibody responses was detected. Reported data highlight the need of considering concomitant pathogens and their possible interactions for a better understanding of diseases and their management in wildlife. PMID- 26267085 TI - Serum concentrations of canine interleukin-1 receptor antagonist protein in healthy dogs after incubation using an autologous serum processing system. AB - The objectives of this study were to optimize and validate a canine IL-1RA ELISA using commercially available reagents and to determine the effect of an autologous serum processing system (IRAP II) on IL-1RA concentrations in canine serum. The clinical detection limit of the optimized ELISA was 188.8 to 39,965.6 pg/mL. The observed-to-expected ratio (O:E) for three serial dilutions for four serum samples ranged from 109.6 to 132.2%. The O:E for four serum samples spiked with four concentrations of canine IL-1 RA ranged from 98.7 to 114.3%. Coefficients of variances for intra- and interassay variability ranged from 1.4 to 3.0 and 6.3 to 9.8, respectively. The ELISA was sensitive, linear, accurate, precise, and reproducible. Mean+/-SD serum concentration of IL-1RA in 12 healthy dogs was 396.6+/-208.0 pg/mL. There was a significant increase in IL-1RA when blood was incubated in the IRAP II system (15,955.0+/-6421.0 pg/mL, P<0.0001). PMID- 26267086 TI - A conformational epitope mapped in the bovine herpesvirus type 1 envelope glycoprotein B by phage display and the HSV-1 3D structure. AB - The selected dodecapeptide (1)DRALYGPTVIDH(12) from a phage-displayed peptide library and the crystal structure of the envelope glycoprotein B (Env gB) from Herpes Simplex Virus type 1 (HSV-1) led us to the identification of a new discontinuous epitope on the Bovine herpesvirus type 1 (BoHV-1) Env gB. In silico analysis revealed a short BoHV-1 gB motif ((338)YKRD(341)) within a epitope region, with a high similarity to the motifs shared by the dodecapeptide N terminal region ((5)YxARD(1)) and HSV-1 Env gB ((326)YARD(329)), in which the (328)Arg residue is described to be a neutralizing antibody target. Besides the characterization of an antibody-binding site of the BoHV-1 Env gB, we have demonstrated that the phage-fused peptide has the potential to be used as a reagent for virus diagnosis by phage-ELISA assay, which discriminated BoHV-1 infected serum samples from negative ones. PMID- 26267087 TI - Torque teno sus virus 1 (TTSuV1) and 2 (TTSuV2) viral loads in serum of postweaning multisystemic wasting syndrome (PMWS)-affected and healthy pigs in Brazil. AB - Associations between Torque teno sus viruses (TTSuVs) and the occurrence of postweaning multisystemic wasting syndrome (PMWS) have been reported with controversial results. Currently, no studies have been performed comparing simultaneously viral loads of TTSuVs and PCV2. To examine the role for TTSuVs in PMWS-affected animals, a SYBR Green-based quantitative PCR (qPCR) was designed to detect and quantify TTSuV1, TTSuV2 and PCV2 genomes in swine sera. TTSuV1 genome loads were significantly higher in healthy adults than in young and SPF animals (p<0.05) suggesting that the prevalence of TTSuV1 infection increases with age and bears no association with PMWS. Regarding TTSuV2, no significant variation was detected in viral loads within any of the groups. As expected, PCV2 genome loads were higher in PMWS-affected swine than in healthy or SPF animals (p<0.001). These findings provide clear evidence to indicate that neither TTSuV1 nor TTSuV2 viral loads have any correlation with the occurrence of PMWS. PMID- 26267088 TI - Evaluation of MALDI-ToF as a method for the identification of bacteria in the veterinary diagnostic laboratory. AB - Matrix-Assisted Laser Desorption Ionisation-Time of Flight (MALDI-ToF) Mass Spectrometry with Bruker MALDI Biotyper software was evaluated as a method for identifying veterinary bacteria. For 620 isolates (~100 bacterial species), identification by MALDI-ToF and non-16S rDNA methods (mainly phenotypic/biochemical) agreed to species-level (95.3%) and to species/genus level (100%), but in the absence of 16S rDNA as a gold standard. For a further panel of 107 anaerobes and 234 aerobes (~100 bacteria species) using 16S rDNA results as the gold standard, MALDI-ToF/biochemical tests showed 97.8/96.6% species-level and 99.6/93.5% genus-level agreement for aerobes and 95.3/93.6% species-level and 100/95.3% genus-level agreement for anaerobes compared to the gold standard. Where results were obtained from direct spots, direct spots overlaid with formic acid and extracts, 89.4% of 180 aerobes and 90.1% of 152 anaerobes were identified by MALDI-ToF. MALDI-ToF was shown to be a rapid and reliable method to identify veterinary bacteria. PMID- 26267089 TI - In vitro and in vivo screening of native lactic acid bacteria toward their selection as a probiotic in broiler chickens. AB - Among 360 isolates from the gastrointestinal tract (GIT) of broilers, eleven isolates which showed in vitro probiotic properties were identified and selected for further tests. After the in vitro screening, three strains were chosen for the in vivo study of persistence of fresh cultures and then one strain was selected for the in vivo study of persistence of lyophilized culture. Lyophilized Lactobacillus salivarius DSPV 001P was capable of persisting in broilers during a complete rearing, even 28 days following cessation of administration. L. salivarius DSPV 001P administered to broilers and recovered from GIT was compared by pulsed-field gel electrophoresis (PFGE) to ensure that the same genotype was persistently identified. A combination of in vitro and in vivo screening of native lactic acid bacteria (LAB) described in this study may offer a method for selecting the most suitable strain for potential application as a broiler probiotic supplement. PMID- 26267090 TI - Evaluation of chemokines CXCL8 and CCL2, serotonin, and vascular endothelial growth factor serum concentrations in healthy dogs from seven breeds with variable predisposition for canine idiopathic pulmonary fibrosis. AB - The West Highland white terrier (WHWT) is particularly prone to canine idiopathic pulmonary fibrosis (CIPF). We hypothesized that higher circulating concentrations of chemokines CXCL8, CCL2, serotonin (5-HT), or vascular endothelial growth factor (VEGF) could serve as predisposing factors for CIPF development in the WHWT breed. Serum samples from 103 healthy dogs of seven different breeds variably predisposed to CIPF were collected. Serum CXCL8 concentrations were higher in healthy WHWT compared with each of the other groups of healthy dogs. Serum CCL2 concentrations were higher in healthy WHWT and Maltese compared with King Charles spaniels and Malinois Belgian shepherds. No relevant inter-breed differences were observed for serum 5-HT concentrations regarding CIPF predisposition. VEGF values from 89.3% of samples tested were below the kit detection limit. In conclusion, high CXCL8 blood concentrations and possibly CCL2 concentrations might be related to the breed predisposition of the WHWT for CIPF and warrants further investigations. PMID- 26267092 TI - In vitro acaricidal properties of Semecarpus anacardium fruit and Datura stramonium leaf extracts against acaricide susceptible (IVRI-I line) and resistant (IVRI-V line) Rhipicephalus (Boophilus) microplus. AB - In an attempt to identify plants having anti-tick properties, the 95% ethanolic and 50% hydro-ethanolic extracts of the fruits of Semecarpus anacardium and leaves of Datura stramonium were evaluated against reference tick lines of Rhipicephalus (Boophilus) microplus. The 95% ethanolic extracts of S. anacardium and D. stramonium caused 50% and 20% mortality, respectively, within 72 h of treatment by adult immersion test. The LC90 value of the ethanolic fruit extract of S. anacardium was determined as 13.5% (CI 12.05-15.12). The extract was also found efficacious (73.3%+/-3.3%) against the multi-acaricide-resistant IVRI-V line of R.(B.) microplus. The S. anacardium extract significantly affected the reproductive physiology of treated ticks by inhibiting the oviposition and was found safe. The HPTLC fingerprinting profile revealed the presence of pyrocatechol as a marker compound. The acaricidal property of S. anacardium against chemical acaricide-resistant R. (B.) microplus was discussed. PMID- 26267091 TI - Characteristics of invasion-reduced hilA gene mutant of Salmonella Enteritidis in vitro and in vivo. AB - Salmonella enterica serovar Enteritidis (Salmonella Enteritidis) is a facultative intracellular pathogen that causes huge losses in poultry industry and also food poisoning in humans due to its being a food-borne pathogen. Functions of Invasion related genes need to be explored, as invasion is a key step for Salmonella infection. In this study, a transposon mutant library of Salmonella Enteritidis isolate SM6 was constructed and screened for the invasion-related genes via incubation with Caco-2 cells. Three stably attenuated mutants were identified for significantly reduced invasion with insertions all in hilA (hyperinvasive locus A) gene. We constructed and evaluated the hilA deletion mutant in vivo and in vitro. SM6?hilA showed significantly reduced ability to invade Caco-2 cells and decreased pathogenicity in chicks. However, the bacterial load and pathological damage in the cecum were significantly higher than those in the SM6 in vivo. Present results provide new evidences for pathogenicity research on Salmonella Enteritidis. PMID- 26267093 TI - Application of acute phase protein measurements in meat extract collected during routine veterinary inspection at abattoirs. AB - The possible application of acute phase protein measurements of meat extract in porcine carcass inspection at abattoir, under routine conditions, was studied. Concentrations of two acute phase proteins, C-reactive protein and haptoglobin, were quantified in 357 samples from carcasses subjected to official veterinary inspection at slaughterhouses. Carcasses were classified according to their sanitary status in five groups of animals ranging from healthy animals, without any organ alteration (group 1), to completely condemned carcasses with gross alteration in several organic systems (group 5). The concentration of both acute phase proteins appeared significantly higher in groups 2 to 5 in comparison to group 1. Sensitivity of these proteins to detect animals with organ alterations was 86% when the values of both proteins were taken into account. The quantification of the levels of acute phase proteins could be of help during routine veterinary meat inspection by offering an objective tool for active disease detection. PMID- 26267094 TI - Effect of various dietary regimens on oral challenge with Mycobacterium avium subsp. paratuberculosis in a rabbit model. AB - Rabbits are susceptible to infection by Mycobacterium avium subspecies paratuberculosis (MAP) in both wildlife and experimental conditions. Under the hypotheses that nutrient balance might influence the establishment of infection, we designed an experiment where MAP intestinal colonization was assessed under three dietary regimens: high fiber, high protein, and regular diet in New Zealand white rabbits submitted to oral challenge with MAP. Lowest weight gain (F=5.17, p=0.024), higher tissue culture positivity rates (X(2)=7.43, p=0.024) and especially extended MAP-compatible lesions (F=5.78, p=0.017) were detected in the regular diet. Taken altogether, results indicate that paratuberculosis infection was achieved affecting mostly regular diet animals and showing that dietary changes may modulate the course of the infection. PMID- 26267095 TI - Dietary effects of Spirulina platensis on hematological and serum biochemical parameters of rainbow trout (Oncorhynchus mykiss). AB - This study evaluated the effects of diets containing 0, 2.5, 5, 7.5 and 10% of Spirulina platensis on hematological and serum biochemical parameters of rainbow trout (Oncorhynchus mykiss). Fish (n=180; 101+/-8 g) were randomly divided into fifteen 300 L fiberglass tanks in triplicates for a period of ten weeks. The RBC, WBC, hemoglobin, total protein and albumin levels increased significantly in the groups supplemented with S. platensis. Dietary inclusion of S. platensis had no significant effects on hematocrit, cholesterol, triglyceride and lactate of the blood. HDL-cholesterol was larger in rainbow trout fed 10% S. platensis in comparison with the other diets, whereas LDL-cholesterol significantly decreased with increasing of S. platensis inclusion. Cortisol and glucose significantly decreased with increasing of S. platensis inclusion. The present results demonstrate that inclusion of 10% S. platensis can be introduced as an immunostimulant in rainbow trout diets. PMID- 26267096 TI - Retrospective seroepidemiological investigations against Morbillivirus, Toxoplasma gondii and Brucella spp. in cetaceans stranded along the Italian coastline (1998-2014). AB - This study reports the results of seroepidemiological investigations carried out against Morbillivirus, Toxoplasma gondii and Brucella spp. on blood serum samples collected from 70 cetacean specimens found stranded along the Italian coastline between 1998 and 2014. A total number of 23 serum samples (32.8%) obtained from Stenella coeruleoalba, Tursiops truncatus, Balaenoptera physalus and Globicephala melas harboured anti-Morbillivirus neutralizing antibodies. Ten sera (16%) collected from S. coeruleoalba and T. truncatus were found positive against T. gondii, while no antibodies against Brucella spp. were found. These data reveal that stranded cetaceans provide a unique opportunity for monitoring the health status of free-ranging animals living in the Mediterranean Sea, in order to investigate the level of exposure of cetacean populations to selected infectious agents representing a serious threat for aquatic mammals. PMID- 26267097 TI - Cloning and expression of mink (Neovison vison) interferon-gamma gene and development of an antiviral assay. AB - Minks (Neovison vison) farming is under a threat of a variety of viral infections with increasingly growing number of breeding in Northeastern and Western China. While interferon is effective in controlling viral infection, IFN among different species rarely share high homology enough to provide cross protective effect on inhibition of virus replication. We cloned, sequenced, phlogenetically analyzed and expressed the miIFN-gamma gene in prokaryotic and eukaryotic cells. The anti vesicular stomatitis virus (VSV) activity of miIFN-gamma protein was tested in MDCK cells using in vitro cytopathic inhibition assay. The recombinant miIFN gamma could inhibit VSV replication in MDCK cells, which was confirmed by that pre-incubation of rabbit anti-miIFN-gamma antibodies with miIFN-gamma abrogated the miIFN-gamma protective effect. Our findings implicated that the miIFN-gamma gene may be a potential counter measure against viral infection in the mink farming. PMID- 26267098 TI - Plasma cytokine levels in dogs undergoing cardiopulmonary bypass. AB - Currently, there are no reports of inflammatory responses to CPB in dogs. We investigated the time course of pro- and anti-inflammatory cytokine levels during and after CPB. ANIMALS: The study group included 11 dogs that underwent mitral valve repair with CPB, and the control group included 7 healthy dogs that underwent ovariohysterectomy. METHODS: Blood samples from the study group dogs were collected before, during and after surgery and analyzed for plasma levels of interleukin-6 (IL-6), tissue necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), white blood cells (WBC), and C-reactive protein (CRP). Each inflammatory parameter was also compared with that of the control group dogs. RESULTS: After CPB, plasma levels of IL-6, WBC counts, and CRP levels were significantly higher than preoperative levels, and IL-6 levels in the study group were significantly higher than those in the control group. CONCLUSIONS: CPB induces a systemic inflammatory response in dogs. PMID- 26267099 TI - Cloning and distribution of neuropeptide W and its receptors in pigs. AB - Neuropeptide W (NPW), a novel hypothalamic peptide, is an endogenous ligand for the orphan G protein-coupled receptors GPR7 (NPBWR1) and GPR8 (NPBWR2). Although several studies have implicated NPW in the regulation of feeding and energy metabolism in many species, the precise physiological function of NPW in pigs remains unclear. In this study, we cloned and sequenced NPW, GPR7, and GPR8 cDNA from pigs. NPW, GPR7, and GPR8 mRNA expression was quantified in the pig brain and peripheral tissues by semiquantitative reverse transcriptase polymerase chain reaction. Immunohistochemistry showed that NPW protein expression was limited in the brain and abundant in peripheral tissues. These results suggest that NPW is involved in the regulation of various physiological functions in pigs. The molecular and morphological data from this study provide a basis for further research on the functions of NPW in pigs. PMID- 26267100 TI - Short communication: Proteomic characterization of tuberculin purified protein derivative from Mycobacterium bovis. AB - Bovine tuberculin purified protein derivative (bPPD) is used as an intradermal test (IT) reagent to detect bovine tuberculosis (bTB) in most countries. Identification of bPPD proteins is critical to understanding the immunological reaction of IT at the molecular level. While bPPD from the United Kingdom (UK) and Brazil (BR) have been recently defined at the proteomic level, bPPD from the Republic of Korea (KR) has not yet been analyzed. Here, bPPD KR proteome was examined for the first time. In total, 271 proteins were identified, including Mycobacterium bovis-specific proteins Mb0854c and Mb2898, and 42 known T cell antigens. On comparing with proteomes of bPPD UK and BR, 33 proteins were found to be common among all three bPPDs, of which 15 proteins were T cell antigens. M. bovis-specific antigens with T cell activity in bPPD may be novel candidates for use as alternatives to currently available bPPD in diagnostics. PMID- 26267101 TI - Apoptosis like cell death in Raillietina echinobothrida induced by resveratrol. AB - Northeast India is geographically nestled as one of the biodiversity hotspots, rich in traditionally used medicinal plants. Resveratrol, a naturally occurring phytoalexin found in berries, peanuts, grapes, red wine and also in numerous anthelmintic plants, has attracted wide interest because of its diverse pharmacological characteristics. Recently, anthelmintic potential of the compound is established. The present study was carried out to understand the possible mechanism of action of resveratrol on poultry tapeworm Raillietina echinobothrida. Resveratrol showed excellent cestocidal activity in a dose dependent manner as revealed through 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) reduction assay. The progressive ultrastructural alterations followed by complete disruption of nuclear membrane, chromosomal condensation and in situ DNA fragmentation confirm the occurrence of apoptosis like cell death. Increased pro-apoptotic caspase activity and significant decreases in mitochondrial membrane potential in R. echinobothrida exposed to resveratrol confirm the involvement of mitochondria in the process of apoptosis. PMID- 26267102 TI - Do umbilical outpouchings affect the behaviour or clinical condition of pigs during 6 h housing in a pre-transport pick-up facility? AB - This study focused on behavioural and clinical effects of umbilical outpouchings (UOs) in pigs. Matched pairs of pigs with UOs (diameter 12 cm; range 4-20; diagnosed p.m. as hernia or non-hernia) and controls (N=28) were compared during a 6-h stay in a pick-up facility. Overall, skin lesion scores were increased after the 6-h stay. Behaviour of the UO-pigs differed from the controls (a shorter latency to lie down (P<0.05) and decreased aggression (P<0.05)). Pigs with umbilical hernia showed e.g. increased sitting (P<0.05) and decreased lying (P<0.05) compared to pigs with non-hernia UOs. No effects of the size of the OUs were found. These results are among the first to establish knowledge about UO pigs and suggest that a stay in a pick-up facility can be challenging for pig welfare. The behavioural findings suggest that UO-pigs, and especially pigs with hernia, may be less fit for mixing and housing in barren environments. PMID- 26267103 TI - Cadmium exposure and consequence for the health and productivity of farmed ruminants. AB - This paper reviews Cd exposure and consequences for the health and productivity of farmed ruminants. In farmed ruminants, Cd exposure may be associated with a number of different activities, including industrial processing, mining, and agricultural practices, and is also higher in soils in some geographic regions. Cd kidney concentrations increase with age and Cd exposure. Although Cd toxicity in farmed ruminants has been demonstrated experimentally, there are no published reports of naturally occurring Cd toxicity in farmed ruminants. Clinical signs of Cd intoxication are unlikely with a daily dietary Cd intake of less than 5 mg/kg feed, which is 5-10 times higher than the maximum permitted Cd concentration in ruminant feed in the European Union. In farmed ruminants, Cd levels in tissue are largely dependent on the Cd content of diet. However, many factors affect Cd availability, relating to soils, plants and the presence of other trace elements including Ca, Cu, Fe, Mn, Mo, Se and Zn. Experimental studies have highlighted the ability of Cd to alter trace element status, and the protective effect of good mineral status, however, there remain gaps in knowledge of the impact of these interactions on the health and productivity of farmed animals. PMID- 26267104 TI - Effects of a synovial flap and gelatin/beta-tricalcium phosphate sponges loaded with mesenchymal stem cells, bone morphogenetic protein-2, and platelet rich plasma on equine osteochondral defects. AB - This study aimed to evaluate the efficacy of a synovial flap and gelatin/beta tricalcium phosphate (GT) sponge loaded with mesenchymal stem cells (MSCs), bone morphogenetic protein-2 (BMP-2), and platelet rich plasma (PRP) for repairing of osteochondral defects in horses. Osteochondral defects were created on the medial condyle of both femurs (n=5). In the test group, a GT sponge loaded with MSCs, BMP-2, and PRP (GT/MSCs/BMP-2/PRP) was inserted into the defect and then covered with a synovial flap. In the control group, the defect was treated only with the GT/MSCs/BMP-2/PRP. The test group showed significantly higher macroscopic scores than the control group. In addition, hyaline cartilaginous tissue was detected in the test group in areas larger than those in the control group. This study demonstrated that the combination of a synovial flap and GT sponge loaded with MSCs, BMP-2, and PRP promoted osteochondral regeneration in an equine model. PMID- 26267105 TI - Validation of behavioural indicators used to assess unconsciousness in sheep. AB - The validity of behavioural indicators to assess unconsciousness under different slaughter conditions is under (inter)national debate. The aim of this study was to validate eyelid-, withdrawal-, threat reflex and rhythmic breathing as indicators to assess unconsciousness in sheep. Sheep were monitored during repeated propofol anaesthesia (n=12) and during non-stunned slaughter (n=22). Changes in the EEG and behavioural indices of consciousness/unconsciousness were assessed and compared in sheep. Threat reflex and rhythmic breathing correlated with EEG activity during propofol anaesthesia whilst absence of non-rhythmic breathing or threat reflex indicated unconsciousness. None of the behavioural indicators correlated with EEG activity during non-stunned slaughter. Absence of regular breathing and eyelid reflex was observed 00:27+/-00:12 min and 00:59+/ 00:17 min (mean+/-SD) respectively after animals were considered unconscious, indicating that absence of regular breathing and eyelid reflex are distinctly conservative indicators of unconsciousness during non-stunned slaughter in sheep. PMID- 26267106 TI - Suitability of a Salmonella control programme based on serology in slaughter heavy pigs. AB - The key component of most European pig Salmonella control programmes is the classification of herds according to seroprevalence at slaughter. The objectives of this study were to estimate the true Salmonella seroprevalence, and investigate the association between the true status of infection and serology in slaughter heavy pigs. Blood of 3340 pigs was collected and tested with ELISA. From 385 pigs, also lymph nodes and cecal content were collected for bacteriology. Analysis was performed in a Bayesian framework. Results showed that a large proportion of pigs was serologically positive (herd seroprevalence 93% and within-herd seroprevalence higher than 81% in half of herds at cut-off 10 OD%). The association between the true status of infection and serology was not significant, and therefore the classification of heavy pig herds according to seroprevalence at slaughter would not be suitable to reduce the risk of introducing Salmonella into the food chain. PMID- 26267107 TI - Serum detection of IgG antibodies against Demodex canis by western blot in healthy dogs and dogs with juvenile generalized demodicosis. AB - The aim of this study was to investigate the presence of canine immunoglobulins (Ig) G against Demodex proteins in the sera of healthy dogs and of dogs with juvenile generalized demodicosis (CanJGD) with or without secondary pyoderma. Demodex mites were collected from dogs with CanJGD. Protein concentration was measured and a western blot technique was performed. Pooled sera from healthy dogs reacted mainly with antigen bands ranging from 55 to 72 kDa. Pooled sera from dogs with CanJGD without secondary pyoderma reacted either with 10 kDa antigen band or 55 to 72 kDa bands. Pooled sera from dogs with CanJGD with secondary pyoderma reacted only with a 10 kDa antigen band. The results of this study suggest that both healthy dogs and dogs with CanJGD develop a humoral response against different proteins of Demodex canis. PMID- 26267108 TI - Morphological and behavioral convergence in extinct and extant bugs: the systematics and biology of a new unusual fossil lace bug from the eocene. AB - The bug Gyaclavator kohlsi Wappler, Guilbert, Wedmann et Labandeira, gen. et sp. nov., represents a new extinct genus of lace bugs (Insecta: Heteroptera: Tingidae) occurring in latest early Eocene deposits of the Green River Formation, from the southern Piceance Basin of Northwestern Colorado, in North America. Gyaclavator can be placed within the Tingidae with certainty, perhaps it is sistergroup to Cantacaderinae. If it belongs to Cantacaderinae, it is the first fossil record of this group for North America. Gyaclavator has unique, conspicuous antennae bearing a specialized, highly dilated distiflagellomere, likely important for intra- or intersex reproductive competition and attraction. This character parallels similar antennae in leaf-footed bugs (Coreidae), and probably is associated with a behavioral convergence as well. PMID- 26267109 TI - Erratum: Cloning, overexpression and biocatalytic exploration of a novel Baeyer Villiger monooxygenase from Aspergillus fumigatus Af293. PMID- 26267110 TI - Construction of a biodynamic model for Cry protein production studies. AB - Mathematical models have been used from growth kinetic simulation to gen regulatory networks prediction for B. thuringiensis culture. However, this culture is a time dependent dynamic process where cells physiology suffers several changes depending on the changes in the cell environment. Therefore, through its culture, B. thuringiensis presents three phases related with the predominance of three major metabolic pathways: vegetative growth (Embded Meyerhof-Parnas pathway), transition (gamma-aminobutiric cycle) and sporulation (tricarboxylic acid cycle). There is not available a mathematical model that relates the different stages of cultivation with the metabolic pathway active on each one of them. Therefore, in the present study, and based on published data, a biodynamic model was generated to describe the dynamic of the three different phases based on their major metabolic pathways. The biodynamic model is used to study the interrelation between the different culture phases and their relationship with the Cry protein production. The model consists of three interconnected modules where each module represents one culture phase and its principal metabolic pathway. For model validation four new fermentations were done showing that the model constructed describes reasonably well the dynamic of the three phases. The main results of this model imply that poly-beta hydroxybutyrate is crucial for endospore and Cry protein production. According to the yields of dipicolinic acid and Cry from poly-beta-hydroxybutyrate, calculated with the model, the endospore and Cry protein production are not just simultaneous and parallel processes they are also competitive processes. PMID- 26267111 TI - Inhibitory effects of H-Ras/Raf-1-binding affibody molecules on synovial cell function. AB - Affibody molecules specific for H-Ras and Raf-1 were evaluated for their ability to inhibit synovial cell function. Affibody molecules targeting H-Ras (Zras122, Zras220, and Zras521) or Raf-1 (Zraf322) were introduced into the MH7A synovial cell line using two delivery methods: transfection with plasmids encoding the affibody molecules or direct introduction of affibody protein using a cell penetrating peptide reagent. Interleukin-6 (IL-6) and prostaglandin E2 (PGE2) production by MH7A cells were analyzed by enzyme-linked immunosorbent assay after stimulation with tumor necrosis factor-alpha (TNF-alpha). Cell proliferation was also analyzed. Phosphorylation of extracellular signal-regulated kinase (ERK) was analyzed by western blot. All affibody molecules could inhibit IL-6 and PGE2 production in TNF-alpha-stimulated MH7A cells. The inhibitory effect was stronger when affibody molecules were delivered as proteins via a cell-penetrating peptide reagent than when plasmid-DNA encoding the affibody moelcules was transfected into the cells. Plasmid-expressed Zras220 inhibited phosphorylation of ERK in TNF alpha-stimulated MH7A cells. Protein-introduced Zraf322 inhibited the production of IL-6 and PGE2 and inhibited cell proliferation in MH7A cells. These findings suggest that affibody molecules specific for H-Ras and Raf-1 can affect intracellular signal transduction through the MAP kinase pathway to inhibit cell proliferation and production of inflammatory mediators by synovial cells. PMID- 26267112 TI - Improved production of poly(lactic acid)-like polyester based on metabolite analysis to address the rate-limiting step. AB - The biosynthesis of poly(lactic acid) (PLA)-like polymers, composed of >99 mol% lactate and a trace amount of 3-hydroxybutyrate, in engineered Corynebacterium glutamicum consists of two steps; the generation of the monomer substrate lactyl coenzyme A (CoA) and the polyhydroxyalkanoate (PHA) synthase-catalyzed polymerization of lactyl-CoA. In order to increase polymer productivity, we explored the rate-limiting step in PLA-like polymer synthesis based on quantitative metabolite analysis using liquid chromatography mass spectroscopy (LC-MS). A significant pool of lactyl-CoA was found during polymer synthesis. This result suggested that the rate-limitation occurred at the polymerization step. Accordingly, the expression level of PHA synthase was increased by means of codon-optimization of the corresponding gene that consequently led to an increase in polymer content by 4.4-fold compared to the control. Notably, the codon optimization did not significantly affect the concentration of lactyl-CoA, suggesting that the polymerization reaction was still the rate-limiting step upon the overexpression of PHA synthase. Another important finding was that the generation of lactyl-CoA was concomitant with a decrease in the acetyl-CoA level, indicating that acetyl-CoA served as a CoA donor for lactyl-CoA synthesis. These results show that obtaining information on the metabolite concentrations is highly useful for improving PLA-like polymer production. This strategy should be applicable to a wide range of PHA-producing systems. PMID- 26267113 TI - Sulfobacillus thermosulfidooxidans strain Cutipay enhances chalcopyrite bioleaching under moderate thermophilic conditions in the presence of chloride ion. AB - Currently more than 90% of the world's copper is obtained through sulfide mineral processing. Among the copper sulfides, chalcopyrite is the most abundant and therefore economically relevant. However, primary copper sulfide bioleaching is restricted due to high ionic strength raffinate solutions and particularly chloride coming from the dissolution of ores. In this work we describe the chalcopyrite bioleaching capacity of Sulfobacillus thermosulfidooxidans strain Cutipay (DSM 27601) previously described at the genomic level (Travisany et al. (2012) Draft genome sequence of the Sulfobacillus thermosulfidooxidans Cutipay strain, an indigenous bacterium isolated from a naturally extreme mining environment in Northern Chile. J Bacteriol 194:6327-6328). Bioleaching assays with the mixotrophic strain Cutipay showed a strong increase in copper recovery from chalcopyrite concentrate at 50 degrees C in the presence of chloride ion, a relevant inhibitory element present in copper bioleaching processes. Compared to the abiotic control and a test with Sulfobacillus acidophilus DSM 10332, strain Cutipay showed an increase of 42 and 69% in copper recovery, respectively, demonstrating its high potential for chalcopyrite bioleaching. Moreover, a genomic comparison highlights the presence of the 2-Haloacid dehalogenase predicted-protein related to a potential new mechanism of chloride resistance in acidophiles. This novel and industrially applicable strain is under patent application CL 2013-03335. PMID- 26267114 TI - L-citrulline production by metabolically engineered Corynebacterium glutamicum from glucose and alternative carbon sources. AB - L-citrulline plays an important role in human health and nutrition and is an intermediate of the L-arginine biosynthetic pathway. L-citrulline is a by-product of L-arginine production by Corynebacterium glutamicum. In this study, C. glutamicum was engineered for overproduction of L-citrulline as major product without L-arginine being produced as by-product. To this end, L-arginine biosynthesis was derepressed by deletion of the arginine repressor gene argR and conversion of L-citrulline towards L-arginine was avoided by deletion of the argininosuccinate synthetase gene argG. Moreover, to facilitate L-citrulline production the gene encoding a feedback resistant N-acetyl L-glutamate kinase argB (fbr) as well as the gene encoding L-ornithine carbamoylphosphate transferase argF were overexpressed. The resulting strain accumulated 44.1 +/- 0.5 mM L-citrulline from glucose minimal medium with a yield of 0.38 +/- 0.01 g[Symbol: see text]g(-1) and a volumetric productivity of 0.32 +/- 0.01 g[Symbol: see text]l(-1)[Symbol: see text]h(-1). In addition, production of L-citrulline from the alternative carbon sources starch, xylose, and glucosamine could be demonstrated. PMID- 26267115 TI - Enhanced ethanol production and reduced glycerol formation in fps1? mutants of Saccharomyces cerevisiae engineered for improved redox balancing. AB - Ethanol is by volume the largest fermentation product. During ethanol production by Saccharomyces cerevisiae about 4-5% of the carbon source is lost to glycerol production. Different approaches have been proposed for improving the ethanol yield while reducing glycerol production. Here we studied the effect of reducing glycerol export/formation through deletion of the aquaglyceroporin gene FPS1 together with expressing gapN encoding NADP(+)-dependent non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase from Streptococcus mutans and overexpressing the ATP-NADH kinase gene UTR1 from S. cerevisiae. This strategy will allow reducing the redox balance problem observed when the glycerol pathway is blocked, and hereby improve ethanol production. We found that our strategy enabled increasing the ethanol yield by 4.6% in the case of the best producing strain, compared to the reference strain, without any major effect on the specific growth rate. PMID- 26267116 TI - ESEA: Discovering the Dysregulated Pathways based on Edge Set Enrichment Analysis. AB - Pathway analyses are playing an increasingly important role in understanding biological mechanism, cellular function and disease states. Current pathway identification methods generally focus on only the changes of gene expression levels; however, the biological relationships among genes are also the fundamental components of pathways, and the dysregulated relationships may also alter the pathway activities. We propose a powerful computational method, Edge Set Enrichment Analysis (ESEA), for the identification of dysregulated pathways. This provides a novel way of pathway analysis by investigating the changes of biological relationships of pathways in the context of gene expression data. Simulation studies illustrate the power and performance of ESEA under various simulated conditions. Using real datasets from p53 mutation, Type 2 diabetes and lung cancer, we validate effectiveness of ESEA in identifying dysregulated pathways. We further compare our results with five other pathway enrichment analysis methods. With these analyses, we show that ESEA is able to help uncover dysregulated biological pathways underlying complex traits and human diseases via specific use of the dysregulated biological relationships. We develop a freely available R-based tool of ESEA. Currently, ESEA can support pathway analysis of the seven public databases (KEGG; Reactome; Biocarta; NCI; SPIKE; HumanCyc; Panther). PMID- 26267118 TI - Urban environment and well-being: cross-cultural studies on Perceived Residential Environment Quality Indicators (PREQIs). AB - Architectural and environmental psychology literature has shown the importance of urban design in provoking stress feelings or enhancing well-being and quality of life. The aim of this contribution is to show the main results of a set of cross cultural survey studies concerning the perceived quality of urban features at the neighbourhood level. A questionnaire was used including the extended or the short version of the 11 scales measuring Perceived Residential Environment Quality Indicators (PREQIs), which cover architectural, social, functional, and contextual aspects. Both versions of PREQIs showed a similar factorial structure and a good (or at least acceptable) reliability across different geographical contexts, even though some differences emerged in those countries that are more distant from the Western linguistic and cultural milieu. The development of tools like PREQIs should increase a "user-centred" vision on urban issues. PMID- 26267117 TI - Oxygen-18 Kinetic Isotope Effects of Nonheme Iron Enzymes HEPD and MPnS Support Iron(III) Superoxide as the Hydrogen Abstraction Species. AB - Nonheme iron oxygenases that carry out four-electron oxidations of substrate have been proposed to employ iron(III) superoxide species to initiate this reaction [Paria, S.; Que, L.; Paine, T. K. Angew. Chem. Int. Ed. 2011, 50, 11129]. Here we report experimental evidence in support of this proposal. (18)O KIEs were measured for two recently discovered mononuclear nonheme iron oxygenases: hydroxyethylphosphonate dioxygenase (HEPD) and methylphosphonate synthase (MPnS). Competitive (18)O KIEs measured with deuterated substrates are larger than those measured with unlabeled substrates, which indicates that C-H cleavage must occur before an irreversible reductive step at molecular oxygen. A similar observation was previously used to implicate copper(II) superoxide in the H-abstraction reactions catalyzed by dopamine beta-monooxygenase [Tian, G. C.; Klinman, J. P. J. Am. Chem. Soc. 1993, 115, 8891] and peptidylglycine alpha-hydroxylating monooxygenase [Francisco, W. A.; Blackburn, N. J.; Klinman, J. P. Biochemistry 2003, 42, 1813]. PMID- 26267119 TI - Effects of a One Year Reusable Contraceptive Vaginal Ring on Vaginal Microflora and the Risk of Vaginal Infection: An Open-Label Prospective Evaluation. AB - BACKGROUND: A contraceptive vaginal ring (CVR) containing Nestorone(r) (NES) and ethinyl estradiol (EE) that is reusable for 1- year (13 cycles) is under development. This study assessed effects of this investigational CVR on the incidence of vaginal infections and change in vaginal microflora. METHODS: There were 120 women enrolled into a NES/EE CVR Phase III trial and a microbiology sub study for up to 1- year of cyclic product use. Gynecological examinations were conducted at baseline, the first week of cycle 6 and last week of cycle 13 (or during early discontinuation visits). Vaginal swabs were obtained for wet mount microscopy, Gram stain and culture. The CVR was removed from the vagina at the last study visit and cultured. Semi-quantitative cultures for Lactobacillus, Gardnerella vaginalis, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, anaerobic gram negative rods (GNRs), Candida albicans and other yeasts were performed on vaginal and CVR samples. Vaginal infections were documented throughout the study. RESULTS: Over 1- year of use, 3.3% of subjects were clinically diagnosed with bacterial vaginosis, 15.0% with vulvovaginal candidiasis, and 0.8% with trichomoniasis. The detection rate of these three infections did not change significantly from baseline to either Cycle 6 or 13. Nugent scores remained stable. H2O2-positive Lactobacillus dominated vaginal flora with a non-significant prevalence increase from 76.7% at baseline to 82.7% at cycle 6 and 90.2% at cycle 13, and a median concentration of 107 colony forming units (cfu) per gram. Although anaerobic GNRs prevalence increased significantly, the median concentration decreased slightly (104 to 103cfu per gram). There were no significant changes in frequency or concentrations of other pathogens. High levels of agreement between vaginal and ring surface microbiota were observed. CONCLUSION: Sustained use of the NES/EE CVR did not increase the risk of vaginal infection and was not disruptive to the vaginal ecosystem. TRIAL REGISTRATION: ClinicalTrials.gov NCT00263341, NCT00455156. PMID- 26267120 TI - Connective tissue adaptations in the fingers of performance sport climbers. AB - This study investigates the changes of the connective tissue in the fingers of performance sport climbers resulting after a minimum of 15 years of climbing. Evaluation was performed by ultrasonography on the palmar side of the fingers (Dig) II-V to measure the thickness of the A2 and A4 annular pulleys, the flexor digitorum superficialis (FDS) and profundus (FDP) tendons and the palmar plates (PP's) of the proximal interphalangeal (PIP) as well as distal interphalangeal (DIP) joint in sagittal and axial direction. Totally, 31 experienced male sport climbers (mean age 37y, 30-48y grade French scale median 8b, range 7b+ to 9a+) participated in the study. The control-group consisted of 20 male non-climbers (age 37y, 30-51y). The A2 and A4 pulleys in climbers were all significantly thicker (A2 Dig III 62%, Dig IV 69%; A4 Dig III 69%, Dig IV 76%) as compared to non-climbers pulleys. All PP's of the DIP joints were also significantly thicker, particularly at Dig III and IV (76 and 67%), whereas the PP's at PIP joints were only scarce significant for three joints. Differences of the diameter of the flexor tendons were less distinct (1-21%) being significant only over the middle phalanx. High load to the fingers of rock climbers after a minimum of 15 years of climbing years induced considerable connective tissue adaptions in the fingers, most distinct at the flexor tendon pulleys and joint capsule (PP) of the DIP joints and well detectable by ultrasound. PMID- 26267121 TI - Retiform hemangioendothelioma treated with conservative therapy: report of a case and review of the literature. AB - BACKGROUND: Retiform hemangioendothelioma (RH) is a locally aggressive vascular tumor. Wide surgical excision with tumor-free margins is the standard treatment strategy. However, surgical excision is not an option for lesions near critical anatomical structures, such as those on the face. We report the case of a patient with retiform hemangioendothelioma that responded to non-surgical treatments. METHODS: We describe the case of a 72-year-old male patient with a retiform hemangioendothelioma on the face that responded to a combination of pulsed dye laser, local corticosteroid injection, and application of imiquimod cream. In addition, we reviewed past case reports of patients with retiform hemangioendothelioma. RESULTS: Thirty-five cases that describe the management of RH, including the present case, have been reported. Review of the cases indicate a relatively low disease-free survival rate in cases that underwent surgical excision as the initial therapy for retiform hemangioendothelioma. CONCLUSION: Surgical excision might not be the best therapeutic option. Local control with conservative therapy is an acceptable strategy for lesions in anatomical regions including the face. PMID- 26267122 TI - Extent of lymph node dissection for adenocarcinoma of the stomach. AB - BACKGROUND: The impact of lymphadenectomy extent on the survival of patients with primary resectable gastric carcinoma is debated. OBJECTIVES: We aimed to systematically review and meta-analyze the evidence on the impact of the three main types of progressively more extended lymph node dissection (that is, D1, D2 and D3 lymphadenectomy) on the clinical outcome of patients with primary resectable carcinoma of the stomach. The primary objective was to assess the impact of lymphadenectomy extent on survival (overall survival [OS], disease specific survival [DSS] and disease free survival [DFS]). The secondary aim was to assess the impact of lymphadenectomy on post-operative mortality. SEARCH METHODS: We searched CENTRAL, MEDLINE and EMBASE until 2001, including references from relevant articles and conference proceedings. We also contacted known researchers in the field. For the updated review, CENTRAL, MEDLINE and EMBASE were searched from 2001 to February 2015. SELECTION CRITERIA: We considered randomized controlled trials (RCTs) comparing the three main types of lymph node dissection (i.e., D1, D2 and D3 lymphadenectomy) in patients with primary non metastatic resectable carcinoma of the stomach. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data from the included studies. Hazard ratios (HR) and relative risks (RR) along with their 95% confidence intervals (CI) were used to measure differences in survival and mortality rates between trial arms, respectively. Potential sources of between-study heterogeneity were investigated by means of subgroup and sensitivity analyses. The same two authors independently assessed the risk of bias of eligible studies according to the standards of the Cochrane Collaboration and the quality of the overall evidence based on the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) criteria. MAIN RESULTS: Eight RCTs (enrolling 2515 patients) met the inclusion criteria. Three RCTs (all performed in Asian countries) compared D3 with D2 lymphadenectomy: data suggested no significant difference in OS between these two types of lymph node dissection (HR 0.99, 95% CI 0.81 to 1.21), with no significant difference in postoperative mortality (RR 1.67, 95% CI 0.41 to 6.73). Data for DFS were available only from one trial and for no trial were DSS data available. Five RCTs (n = 3 European; n = 2 Asian) compared D2 to D1 lymphadenectomy: OS (n = 5; HR 0.91, 95% CI 0.71 to 1.17) and DFS (n=3; HR 0.95, 95% CI 0.84 to 1.07) findings suggested no significant difference between these two types of lymph node dissection. In contrast, D2 lymphadenectomy was associated with a significantly better DSS compared to D1 lymphadenectomy (HR 0.81, 95% CI 0.71 to 0.92), the quality of the body of evidence being moderate; however, D2 lymphadenectomy was also associated with a higher postoperative mortality rate (RR 2.02, 95% CI 1.34 to 3.04). AUTHORS' CONCLUSIONS: D2 lymphadenectomy can improve DSS in patients with resectable carcinoma of the stomach, although the increased incidence of postoperative mortality reduces its therapeutic benefit. PMID- 26267123 TI - Assessment of liver fibrosis by variable flip angle T1 mapping at 3.0T. AB - PURPOSE: To evaluate the possibility of using a variable flip angle (VFA) T1 mapping technique to diagnose liver fibrosis. MATERIALS AND METHODS: Liver fibrosis was induced in rabbits by repetitive administration of carbon tetrachloride (CCl4 ). T1 -weighted magnetic resonance imaging (MRI) was performed in 29 animals (liver fibrosis, n = 18; control, n = 11) using a series of nonenhanced liver acquisition volume acceleration (LAVA) with VFAs at 3.0T. Hepatic T1 relaxation times were measured via regions of interest, which were correlated with subsequent histologic confirmation. The results of T1 mapping in assessment of liver fibrosis were compared with that of apparent diffusion coefficient (ADC) values. RESULTS: The mean T1 relaxation time of the control group was the lowest (250.07 +/- 88.12 msec), followed by the nonadvanced fibrosis group (387.83 +/- 166.58 msec) and the advanced fibrosis group (496.90 +/- 291.24 msec). T1 relaxation time measurements differed significantly between the liver fibrosis group and control group (P < 0.05), with a trend of increased mean T1 relaxation times as the fibrotic stage increased. Statistically significant differences were observed between the control group and the nonadvanced fibrosis group (P < 0.05), however with much overlap between the less severe stages. In discriminating between the control group and liver fibrosis group, stage F0-1 (control and stage F1) and stage F2-3, stage F0-2 (control and stage F1-2) and stage F3, area under the receiver operating characteristic (ROC) curves were 0.803 (cutoff value 273.01 msec), 0.712 (cutoff value 371.54 msec), and 0.696 (cutoff value 276.99 msec), respectively. No difference was found between T1 relaxation times and ADC values in assessment of liver fibrosis in our study. CONCLUSION: VFA T1 mapping may become a noninvasive imaging tool for the diagnosis of liver fibrosis. PMID- 26267124 TI - Commentary on Sources of Ostracism Research. AB - This article briefly introduces and provides commentary on this special issue, "Investigating How Individuals Feel Ostracizing Others" in the Journal of Social Psychology. This commentary uses first-person recollections from early ostracism studies to help frame the special issue in the larger scope of ostracism research. Modern ostracism research started in the early 1990s and hundreds of studies have advanced our understanding of this phenomenon. However, the preponderance of research has focused on the target of ostracism (those being ostracized) and relied primarily on a single method in experimental studies. The present special issue includes articles that employed a variety of research approaches and focused exclusively on the sources (those who do the ostracism). Finally, this commentary invites researchers to more fully investigate this understudied aspect of a common phenomenon that people are likely to engage in regularly. PMID- 26267125 TI - Ostracizing for a Reason: A Novel Source Paradigm for Examining the Nature and Consequences of Motivated Ostracism. AB - Ostracism, a complex social phenomenon, involves both targets (ostracized individuals) and sources (ostracizers). The current experiment redressed a gap in the ostracism literature by devising a novel, three-phase paradigm to investigate motivated ostracizing. In the current study, 83 females were assigned to one of four conditions during a Cyberball game: motivated sources chose to ostracize an obnoxious fellow player, induced sources ostracized a fellow player at the behest of the experimenter, targets were ostracized, and included participants received the ball proportionately. Analysis of participants' primary needs, emotions, ratings of their co-players, and behavior toward their co-players indicated that being the target of ostracism was a robustly aversive experience. Both motivated and induced sources reported fortified control. Moreover, a motive for ostracizing influenced source experience: induced sources experienced greater levels of negative moral emotion and behaved more prosocially toward their target than motivated sources. The flexibility and demonstrated impact of this novel paradigm adds to the toolkit available to researchers interested in expanding insight into the psychological processes underlying, and the motivational and behavioral outcomes of being, a source of ostracism. PMID- 26267126 TI - Ostracism in Everyday Life: The Effects of Ostracism on Those Who Ostracize. AB - Ostracism is a negative interpersonal experience that has been studied primarily in laboratory settings. Moreover, these studies have focused primarily on how people feel when they have been ostracized. The present study extended this research by investigating ostracism as it occurs in daily life, focusing on how people feel about ostracizing someone. Using a method modeled after the Rochester Interaction Record (RIR), for two weeks, 64 participants (adults residing in the community) described what happened each time they ostracized someone. The questions in the diary were based on Williams's (2001) need-threat model of ostracism. Most ostracism episodes were directed toward people of equal status, and participants reported lower levels of belonging but higher levels of control after ostracizing someone. Punitive ostracism was associated with more positive outcomes for the source than when people ostracized someone for other reasons. PMID- 26267127 TI - Who Would Do That? A Theory-Based Analysis of Narratives of Sources of Family Ostracism. AB - There are many benefits derived from families, but not all family members are loving and accepting. Family members may act as sources of ostracism (people or groups who ostracize another person/group). We suggest sources engage in family ostracism for extended periods, their motives fit with prior theoretical models, and trait-level forgiveness may help understand source behavior. We analyzed data from 63 narratives and questionnaires to investigate the motives, power dynamics, and psychological correlates of sources of family ostracism. We found sources of ostracism are often of equal status to the targets of ostracism, and termination often occurs informally or is prompted by major changes in the family (e.g., birth, move). Also, sources of ostracism are often targets themselves suggesting family ostracism may be reciprocal in nature. Our findings support existing theory, but suggest ostracism in families has unique dynamics not captured in laboratory designs. PMID- 26267128 TI - Righting the Wrong: Reparative Coping After Going Along With Ostracism. AB - Most of the focus within the ostracism literature concerns the negative effects on the ostracized and how they cope following ostracism. Research is now beginning to illuminate negative psychological effects for ostracizers, yet no studies to date have examined their coping responses. This study continues this line of inquiry focusing on experiences of going along with ostracism, both by employing a face-to-face interaction and by exploring prosocial versus antisocial coping reactions in ostracizers. Results reveal that compared to those in a neutral condition, compliant ostracizers suffered because ostracizing someone else frustrated their psychological needs for autonomy and relatedness. Further, when given the chance, ostracizers were more inclusive of the person they previously ostracized. Discussion considers important avenues for future research as well as implications of results. PMID- 26267129 TI - The Role of Burden and Deviation in Ostracizing Others. AB - Ostracism (being excluded and ignored) is a painful experience, so why do individuals ostracize others? Previous research suggests individuals often ostracize those who are deviate, but not always. We posit that there may be two types of deviation, burdensome and non-burdensome, and the former is most likely to be ostracized. Study 1 manipulated burdensome deviation by programming a group member to perform more slowly (8 or 16 sec.) than others (4 sec.) in a virtual ball-toss game. Participants perceived slower players as more burdensome and deviate than normal speed players. Additionally, participants ostracized (gave fewer ball tosses to) the slowest player. Study 2 examined participant responses to both burdensome deviation (8- and 16-sec. players) and non-burdensome deviation (goth appearance). Participants again perceived the slower players to be burdensome and deviate, and ostracized them. They perceived the goth player to be deviate but not burdensome and did not ostracize this player. PMID- 26267130 TI - Atimia: A New Paradigm for Investigating How Individuals Feel When Ostracizing Others. AB - To date, researchers studying ostracism (being excluded and ignored) focused on examining the consequences of ostracism. However, researchers have not yet systematically investigated why individuals ostracize others. One impediment to this research is lacking multiple means to successfully induce individuals to be sources, those who ostracize others. Using Cyberball, researchers found participants ostracized a player delaying the game. To aid in systematic research on sources, we developed the game Atimia. In Atimia, players took turns solving remote associate word items and we varied the performance of a computer controlled player to perform equal to or significantly worse than the group. Without prompting, participants ostracized a poor- versus equal-performing player more and found the poor-performing player burdensome, less likable, and less desirable to work with on a future task. Study outcomes suggest Atimia is a viable paradigm for investigating sources of ostracism. PMID- 26267131 TI - How Does the Source of Rejection Perceive Innocent Victims? AB - Prior studies have consistently revealed a strong positive association between general just-world beliefs and victim blaming. The present research aims to extend the literature by testing whether an act of social rejection overrides the influence of general just-world beliefs on victim blaming. Building upon the theory of moral compensation that people are more prosocial after behaving undesirably, we predicted that people should be less likely to blame an innocent victim after rejecting another person and that general just-world beliefs were not associated with victim blaming among the sources of rejection. To test these predictions, participants first completed a measure of general just-world beliefs and then recalled a past incident in which they rejected or accepted another person. They then read a scenario about school bullying and made attributions for the victim's suffering. The results supported our predictions and the implications of the study are discussed. PMID- 26267132 TI - Insufficient Justification for Exclusion Prompts Compensatory Behavior. AB - This experiment examined participants' compensatory behavior toward an excluded stranger. Participants engaged in a four-person social introductions task and rank-ordered each other member of the group; the lowest ranked person was excluded from a subsequent game. Using a 2 * 2 design, participants were randomly assigned to a justification condition (insufficient vs. sufficient) and to an exclusion responsibility condition (responsible for exclusion vs. exclusion by random selection). Results revealed that after limited introductions (i.e., insufficient justification for one's ranking decision), being responsible for the exclusion prompted compensatory behavior toward the excluded stranger. However, after extended introductions (i.e., sufficient justification of one's ranking decision), participants did not compensate the excluded person. These results suggest that insufficient justification for exclusion may lead to compensatory behavior, when one is responsible for the exclusion. PMID- 26267133 TI - Measurement of separase proteolytic activity in single living cells by a fluorogenic flow cytometry assay. AB - ESPL1/Separase, an endopeptidase, is required for centrosome duplication and separation of sister-chromatides in anaphase of mitosis. Overexpression and deregulated proteolytic activity of Separase as frequently observed in human cancers is associated with the occurrence of supernumerary centrosomes, chromosomal missegregation and aneuploidy. Recently, we have hypothesized that increased Separase proteolytic activity in a small subpopulation of tumor cells may serve as driver of tumor heterogeneity and clonal evolution in chronic myeloid leukemia (CML). Currently, there is no quantitative assay to measure Separase activity levels in single cells. Therefore, we have designed a flow cytometry-based assay that utilizes a Cy5- and rhodamine 110 (Rh110)-biconjugated Rad21 cleavage site peptide ([Cy5-D-R-E-I-M-R]2-Rh110) as smart probe and intracellular substrate for detection of Separase enzyme activity in living cells. As measured by Cy5 fluorescence the cellular uptake of the fluorogenic peptide was fast and reached saturation after 210 min of incubation in human histiocytic lymphoma U937 cells. Separase activity was recorded as the intensity of Rh110 fluorescence released after intracellular peptide cleavage providing a linear signal gain within a 90-180 min time slot. Compared to conventional cell extract-based methods the flow cytometric assay delivers equivalent results but is more reliable, bypasses the problem of vague loading controls and unspecific proteolysis associated with whole cell extracts. Especially suited for the investigaton of blood- and bone marrow-derived hematopoietic cells the flow cytometric Separase assay allows generation of Separase activity profiles that tell about the number of Separase positive cells within a sample i.e. cells that currently progress through mitosis and about the range of intercellular variation in Separase activity levels within a cell population. The assay was used to quantify Separase proteolytic activity in leukemic cell lines and peripheral blood samples from leukemia patients. PMID- 26267135 TI - A recurrent vesiculobullous eruption on the head, trunk, and extremities. Bullous Sweet's syndrome. PMID- 26267134 TI - New Mechanisms of Flucytosine Resistance in C. glabrata Unveiled by a Chemogenomics Analysis in S. cerevisiae. AB - 5-Flucytosine is currently used as an antifungal drug in combination therapy, but fungal pathogens are rapidly able to develop resistance against this drug, compromising its therapeutic action. The understanding of the underlying resistance mechanisms is crucial to deal with this problem. In this work, the S. cerevisiae deletion mutant collection was screened for increased resistance to flucytosine. Through this chemogenomics analysis, 183 genes were found to confer resistance to this antifungal agent. Consistent with its known effect in DNA, RNA and protein synthesis, the most significant Gene Ontology terms over-represented in the list of 5-flucytosine resistance determinants are related to DNA repair, RNA and protein metabolism. Additional functional classes include carbohydrate and nitrogen-particularly arginine-metabolism, lipid metabolism and cell wall remodeling. Based on the results obtained for S. cerevisiae as a model system, further studies were conducted in the pathogenic yeast Candida glabrata. Arginine supplementation was found to relieve the inhibitory effect exerted by 5 flucytosine in C. glabrata. Lyticase susceptibility was found to increase within the first 30min of 5-flucytosine exposure, suggesting this antifungal drug to act as a cell wall damaging agent. Upon exponential growth resumption in the presence of 5-flucytosine, the cell wall exhibited higher resistance to lyticase, suggesting that cell wall remodeling occurs in response to 5-flucytosine. Additionally, the aquaglyceroporin encoding genes CgFPS1 and CgFPS2, from C. glabrata, were identified as determinants of 5-flucytosine resistance. CgFPS1 and CgFPS2 were found to mediate 5-flucytosine resistance, by decreasing 5 flucytosine accumulation in C. glabrata cells. PMID- 26267136 TI - The Mechanism by which 146-N-Glycan Affects the Active Site of Neuraminidase. AB - One of the most conserved glycosylation sites of neuraminidase (NA) is 146-N glycan. This site is adjacent to the 150-cavity of NA, which is found within the active site and thought to be a target for rational drug development against the antiviral resistance of influenza. Here, through a total of 2.4 MUs molecular dynamics (MD) simulations, we demonstrated that 146-N-glycan can stabilize the conformation of the 150-loop that controls the volume of the 150-cavity. Moreover, with 146-N-glycan, our simulation result was more consistent with crystal structures of NAs than simulations conducted without glycans. Cluster analysis of the MD trajectories showed that 146-N-glycan adopted three distinct conformations: monomer-bridged, dimer-bridged and standing. Of these conformations, the dimer-bridged 146-N-glycan was the most stable one and contributed to stabilization of the 150-loop conformation. Furthermore, our simulation revealed that various standing conformations of 146-N-glycan could block the entrance of the binding pocket. This result was consistent with experimental data and explained the relatively low activity of inhibitors with flexible substituents toward the 150-cavity. Together, our results lead us to hypothesize that rigid and hydrophobic substituents could serve as better inhibitors targeting the 150-cavity. PMID- 26267137 TI - Spatial and Temporal Characteristics of Historical Oil and Gas Wells in Pennsylvania: Implications for New Shale Gas Resources. AB - Recent large-scale development of oil and gas from low-permeability unconventional formations (e.g., shales, tight sands, and coal seams) has raised concern about potential environmental impacts. If left improperly sealed, legacy oil and gas wells colocated with that new development represent a potential pathway for unwanted migration of fluids (brine, drilling and stimulation fluids, oil, and gas). Uncertainty in the number, location, and abandonment state of legacy wells hinders environmental assessment of exploration and production activity. The objective of this study is to apply publicly available information on Pennsylvania oil and gas wells to better understand their potential to serve as pathways for unwanted fluid migration. This study presents a synthesis of historical reports and digital well records to provide insights into spatial and temporal trends in oil and gas development. Areas with a higher density of wells abandoned prior to the mid-20th century, when more modern well-sealing requirements took effect in Pennsylvania, and areas where conventional oil and gas production penetrated to or through intervals that may be affected by new Marcellus shale development are identified. This information may help to address questions of environmental risk related to new extraction activities. PMID- 26267138 TI - Guidelines for the Treatment of Severe Traumatic Brain Injury: Are They Used? PMID- 26267139 TI - Bocavirus Infection in Otherwise Healthy Children with Respiratory Disease. AB - To evaluate the role of human bocavirus (hBoV) as a causative agent of respiratory disease, the importance of the viral load in respiratory disease type and severity and the pathogenicity of the different hBoV species, we studied all hBoV-positive nasopharyngeal samples collected from children who attended an emergency room for a respiratory tract infection during three winters (2009-2010, 2011-2012, and 2013-2014). Human bocavirus was detected using the respiratory virus panel fast assay and real-time PCR. Of the 1,823 nasopharyngeal samples, 104 (5.7%) were positive for hBoV; a similar prevalence was observed in all three periods studied. Among hBoV-infected children, 53.8% were between 1-2 years old, and hBoV was detected alone in 57/104 (54.8%) cases. All of the detected hBoV strains belonged to genotype 1. The median hBoV load was significantly higher in samples containing strains with both the N546H and T590S mutations compared to other samples (p<0.05). Children with a single hBoV-1 infection more frequently had upper respiratory tract infections (URTIs) than those who were co-infected (37.0% vs 17.8%, respectively, p = 0.04). The duration of hospitalization was longer among children with high viral loads than that observed among children with low viral loads (8.0 +/-2.2 days vs 5.0 +/-1.5 days, respectively, p = 0.03), and the use of aerosol therapy was more frequent among children with high viral loads than among those with low viral loads (77.1% vs 55.7%, respectively, p = 0.04). This study shows that hBoV is a relatively uncommon but stable infectious agent in children and that hBoV1 seems to be the only strain detected in Italy in respiratory samples. From a clinical point of view, hBoV1 seems to have in the majority of healthy children relatively low clinical relevance. Moreover, the viral load influences only the duration of hospitalization and the use of aerosol therapy without any association with the site of the respiratory disease. PMID- 26267140 TI - Malignant Ureteral Obstruction: Functional Duration of Metallic versus Polymeric Ureteral Stents. AB - BACKGROUND: Ureteral obstruction caused by extrinsic compression is often associated with intra-abdominal cancers. Internal drainage with ureteral stents is typically the first-line therapy to relieve such obstructions. Novel designs of ureteral stents made of different materials have been invented to achieve better drainage. In this study, we described the functional outcomes of a Resonance metallic ureteral stent (Cook Medical, Bloomington, Indiana, USA) in patients with malignant ureteral obstruction and compare the functional duration of Resonance stents with regular polymeric stents in the same cohort. METHODS: Cancer patients who received polymeric stents and subsequent Resonance stents for ureteral obstruction between July 2009 and November 2012 were included in a chart review. Stent failure was detected by clinical symptoms, imaging studies, and renal function tests. The functional durations of each stent were calculated, and possible factors affecting stent patency were investigated. RESULTS: A total of 50 stents were successfully inserted into 50 ureteral units in 42 patients with malignant ureteral obstruction. There were 7 antegrade stents and 43 retrograde stents. There were no major complications. Stent-related symptoms were similar in both kinds of stents. After polymeric stents were replaced with Resonance metallic stents, hydronephrosis subsided or remained stable in 90% (45/50) of the ureteral units. Serum creatinine decreased or remained stable in 90% (38/42) of these patients. The Resonance stent exhibited a mean increase in functional duration of 4 months compared with the polymeric stents (p<0.0001), and 50% (25/50) of the Resonance stents exhibited a significant increase in functional duration (more than 3 months). Pre-operative serum creatinine < 2 was associated with a substantial increase in stent duration. CONCLUSIONS: Resonance stents are effective and safe in relieving malignant ureteral obstructions after polymeric stents failure. Resonance stents can provide a longer functional duration than polymeric stents and should be offered as an option for internal drainage. PMID- 26267141 TI - Evaluation of Integrated Community Case Management in Eight Districts of Central Uganda. AB - OBJECTIVE: Evidence is limited on whether Integrated Community Case Management (iCCM) improves treatment coverage of the top causes of childhood mortality (acute respiratory illnesses (ARI), diarrhoea and malaria). The coverage impact of iCCM in Central Uganda was evaluated. METHODS: Between July 2010 and December 2012 a pre-post quasi-experimental study in eight districts with iCCM was conducted; 3 districts without iCCM served as controls. A two-stage household cluster survey at baseline (n = 1036 and 1042) and end line (n = 3890 and 3844) was done in the intervention and comparison groups respectively. Changes in treatment coverage and timeliness were assessed using difference in differences analysis (DID). Mortality impact was modelled using the Lives Saved Tool. FINDINGS: 5,586 Village Health Team members delivered 1,907,746 treatments to children under age five. Use of oral rehydration solution (ORS) and zinc treatment of diarrhoea increased in the intervention area, while there was a decrease in the comparison area (DID = 22.9, p = 0.001). Due to national stock outs of amoxicillin, there was a decrease in antibiotic treatment for ARI in both areas; however, the decrease was significantly greater in the comparison area (DID = 5.18; p<0.001). There was a greater increase in Artemisinin Combination Therapy treatment for fever in the intervention areas than in the comparison area but this was not significant (DID = 1.57, p = 0.105). In the intervention area, timeliness of treatments for fever and ARI increased significantly higher in the intervention area than in the comparison area (DID = 2.12, p = 0.029 and 7.95, p<0.001, respectively). An estimated 106 lives were saved in the intervention area while 611 lives were lost in the comparison area. CONCLUSION: iCCM significantly increased treatment coverage for diarrhoea and fever, mitigated the effect of national stock outs of amoxicillin on ARI treatment, improved timeliness of treatments for fever and ARI and saved lives. PMID- 26267142 TI - Custom 4-Plex DiLeu Isobaric Labels Enable Relative Quantification of Urinary Proteins in Men with Lower Urinary Tract Symptoms (LUTS). AB - The relative quantification of proteins using liquid chromatography mass spectrometry (LC-MS) has allowed researchers to compile lists of potential disease markers. These complex quantitative workflows often include isobaric labeling of enzymatically-produced peptides to analyze their relative abundances across multiple samples in a single LC-MS run. Recent efforts by our lab have provided scientists with cost-effective alternatives to expensive commercial labels. Although the quantitative performance of these dimethyl leucine (DiLeu) labels has been reported using known ratios of complex protein and peptide standards, their potential in large-scale proteomics studies using a clinically relevant system has never been investigated. Our work rectifies this oversight by implementing 4-plex DiLeu to quantify proteins in the urine of aging human males who suffer from lower urinary tract symptoms (LUTS). Protein abundances in 25 LUTS and 15 control patients were compared, revealing that of the 836 proteins quantified, 50 were found to be differentially expressed (>20% change) and statistically significant (p-value <0.05). Gene ontology (GO) analysis of the differentiated proteins showed that many were involved in inflammatory responses and implicated in fibrosis. While confirmation of individual protein abundance changes would be required to verify protein expression, this study represents the first report using the custom isobaric label, 4-plex DiLeu, to quantify protein abundances in a clinically relevant system. PMID- 26267143 TI - A Bayesian Attractor Model for Perceptual Decision Making. AB - Even for simple perceptual decisions, the mechanisms that the brain employs are still under debate. Although current consensus states that the brain accumulates evidence extracted from noisy sensory information, open questions remain about how this simple model relates to other perceptual phenomena such as flexibility in decisions, decision-dependent modulation of sensory gain, or confidence about a decision. We propose a novel approach of how perceptual decisions are made by combining two influential formalisms into a new model. Specifically, we embed an attractor model of decision making into a probabilistic framework that models decision making as Bayesian inference. We show that the new model can explain decision making behaviour by fitting it to experimental data. In addition, the new model combines for the first time three important features: First, the model can update decisions in response to switches in the underlying stimulus. Second, the probabilistic formulation accounts for top-down effects that may explain recent experimental findings of decision-related gain modulation of sensory neurons. Finally, the model computes an explicit measure of confidence which we relate to recent experimental evidence for confidence computations in perceptual decision tasks. PMID- 26267145 TI - Effects of age and cognition on a cross-cultural paediatric adaptation of the Sniffin' Sticks Identification Test. AB - OBJECTIVES: To study the effects of age and cognition on the performance of children aged 3 to 18 years on a culturally adapted version of the 16 item smell identification test from Sniffin' Sticks (SS16). METHODS: A series of pilots were conducted on 29 children aged 3 to 18 years old and 23 adults to produce an adapted version of the SS16 suitable for Brazilian children (SS16-Child). A final version was applied to 51 children alongside a picture identification test (PIT SS16-Child) to access cognitive abilities involved in the smell identification task. In addition 20 adults performed the same tasks as a comparison group. RESULTS: The final adapted SS16-Child was applied to 51 children with a mean age of 9.9 years (range 3-18 years, SD=4.25 years), of which 68.3% were girls. There was an independent effect of age (p<0.05) and PIT-SS16-Child (p<0.001) on the performance on the SS16-Child, and older children reached the ceiling for scoring in the cognitive and olfactory test. Pre-school children had difficulties identifying items of the test. DISCUSSION/CONCLUSIONS: A cross-culturally adapted version of the SS16 can be used to test olfaction in children but interpretation of the results must take age and cognitive abilities into consideration. PMID- 26267144 TI - Mucosal B Cells Are Associated with Delayed SIV Acquisition in Vaccinated Female but Not Male Rhesus Macaques Following SIVmac251 Rectal Challenge. AB - Many viral infections, including HIV, exhibit sex-based pathogenic differences. However, few studies have examined vaccine-related sex differences. We compared immunogenicity and protective efficacy of monomeric SIV gp120 with oligomeric SIV gp140 in a pre-clinical rhesus macaque study and explored a subsequent sex bias in vaccine outcome. Each immunization group (16 females, 8 males) was primed twice mucosally with replication-competent Ad-recombinants encoding SIVsmH4env/rev, SIV239gag and SIV239nefDelta1-13 and boosted twice intramuscularly with SIVmac239 monomeric gp120 or oligomeric gp140 in MF59 adjuvant. Controls (7 females, 5 males) received empty Ad and MF59. Up to 9 weekly intrarectal challenges with low-dose SIVmac251 were administered until macaques became infected. We assessed vaccine-induced binding, neutralizing, and non-neutralizing antibodies, Env-specific memory B cells and plasmablasts/plasma cells (PB/PC) in bone marrow and rectal tissue, mucosal Env-specific antibodies, and Env-specific T-cells. Post-challenge, only one macaque (gp140-immunized) remained uninfected. However, SIV acquisition was significantly delayed in vaccinated females but not males, correlated with Env-specific IgA in rectal secretions, rectal Env-specific memory B cells, and PC in rectal tissue. These results extend previous correlations of mucosal antibodies and memory B cells with protective efficacy. The gp140 regimen was more immunogenic, stimulating elevated gp140 and cyclic V2 binding antibodies, ADCC and ADCP activities, bone marrow Env-specific PB/PC, and rectal gp140-specific IgG. However, immunization with gp120, the form of envelope immunogen used in RV144, the only vaccine trial to show some efficacy, provided more significant acquisition delay. Further over 40 weeks of follow-up, no gp120 immunized macaques met euthanasia criteria in contrast to 7 gp140-immunized and 2 control animals. Although males had higher binding antibodies than females, ADCC and ADCP activities were similar. The complex challenge outcomes may reflect differences in IgG subtypes, Fc glycosylation, Fc-R polymorphisms, and/or the microbiome, key areas for future studies. This first demonstration of a sex-difference in SIV vaccine-induced protection emphasizes the need for sex-balancing in vaccine trials. Our results highlight the importance of mucosal immunity and memory B cells at the SIV exposure site for protection. PMID- 26267146 TI - Hypoxia-induced DNp73 stabilization regulates Vegf-A expression and tumor angiogenesis similar to TAp73. AB - P73, the homolog of p53, exists in 2 major forms: either as a pro-apoptotic TAp73 or an amino-terminally truncated DNp73, the latter lacking the first transactivation domain. While TAp73s tumor suppressive functions have been established, DNp73 is an anti-apoptotic protein conferring chemoresistance and is associated with poor survival. However, both forms are variably overexpressed in many human cancers. In this context, we have recently demonstrated that TAp73 is stabilized by hypoxia, a tumor-relevant condition that is associated with cell survival, via HIF-1alpha-mediated suppression of Siah1 E3 ligase that degrades TAp73. Consequently, hypoxic signals lead to TAp73-mediated activation of several angiogenic genes and blood vessel formation, thereby supporting tumorigenesis. We show here that, similar to TAp73, DNp73 is stabilized by hypoxia in a HIF-1alpha dependent manner, which otherwise is degraded by Siah1. Moreover, DNp73 is capable of inducing the expression of Vegf-A, the prototypic angiogenic gene, and loss of DNp73 expression results in reduction in tumor vasculature and size. These data therefore indicate a common mode of regulation for both p73 forms by hypoxia, resulting in the promotion of angiogenesis and tumor growth, highlighting common functionality of these antagonistic proteins under specific physiological contexts. PMID- 26267147 TI - A novel FoxD3 Variant Is Associated With Vitiligo and Elevated Thyroid Auto Antibodies. AB - CONTEXT: Vitiligo frequently coincides with autoimmune endocrinopathies, particularly Hashimoto's thyroiditis (HT). Genetic susceptibility may underlie this coincident occurrence. One candidate region is the autoimmunity susceptibility locus on chromosome 1, which encompasses forkhead transcription factor D3 (FoxD3), a gene involved in embryonal melanogenesis. We identified a promotor variant (rs78645479) in an index case of vitiligo + HT + candidiasis and evaluated its clinical and functional relevance. DESIGN: We genotyped 281 patients with variable autoimmune endocrinopathies: HT, Graves' disease (GD), type 1 diabetes (T1D), Addison's disease (AD), autoimmune polyglandular syndrome (APS), and/or vitiligo and 1858 controls. Furthermore, we experimentally assessed the effect of the variant on promotor activity and assessed the expression of FoxD3 in human thyroid tissue samples. RESULTS: Patients with vitiligo had a higher frequency of the risk allele (30%) compared with healthy controls (18.2%). In addition, the variant was associated with the incidence of elevated anti-TPO antibodies and anti-Tg antibodies, but not with TSH, FT3, or FT4 levels and also not with GD, T1D, AD, or APS. Functionally, the variant increased transcriptional activity in Jurkat and in Hek293 cells. We confirmed gene expression of FoxD3 in human thyroid tissue, which seemed elevated in thyroid tissue samples of some patients with GD and nonautoimmune goiter but not in patients with HT. CONCLUSION: In addition to a possible association of rs78645479 in FoxD3 with vitiligo, our data on the association of this FoxD3 variant with thyroid autoantibodies suggest a potential involvement of FoxD3 in thyroid immunoregulation. PMID- 26267149 TI - The application of antitumor drug-targeting models on liver cancer. AB - Hepatocarcinoma animal models, such as the induced tumor model, transplanted tumor model, gene animal model, are significant experimental tools for the evaluation of targeting drug delivery system as well as the pre-clinical studies of liver cancer. The application of antitumor drug-targeting models not only furnishes similar biological characteristics to human liver cancer but also offers guarantee of pharmacokinetic indicators of the liver-targeting preparations. In this article, we have reviewed some kinds of antitumor drug targeting models of hepatoma and speculated that the research on this field would be capable of attaining a deeper level and expecting a superior achievement in the future. PMID- 26267148 TI - Flow Cytometric Analysis of Myeloid Cells in Human Blood, Bronchoalveolar Lavage, and Lung Tissues. AB - Clear identification of specific cell populations by flow cytometry is important to understand functional roles. A well-defined flow cytometry panel for myeloid cells in human bronchoalveolar lavage (BAL) and lung tissue is currently lacking. The objective of this study was to develop a flow cytometry-based panel for human BAL and lung tissue. We obtained and performed flow cytometry/sorting on human BAL cells and lung tissue. Confocal images were obtained from lung tissue using antibodies for cluster of differentiation (CD)206, CD169, and E cadherin. We defined a multicolor flow panel for human BAL and lung tissue that identifies major leukocyte populations. These include macrophage (CD206(+)) subsets and other CD206(-) leukocytes. The CD206(-) cells include: (1) three monocyte (CD14(+)) subsets, (2) CD11c(+) dendritic cells (CD14(-), CD11c(+), HLA-DR(+)), (3) plasmacytoid dendritic cells (CD14(-), CD11c(-), HLA-DR(+), CD123(+)), and (4) other granulocytes (neutrophils, mast cells, eosinophils, and basophils). Using this panel on human lung tissue, we defined two populations of pulmonary macrophages: CD169(+) and CD169(-) macrophages. In lung tissue, CD169(-) macrophages were a prominent cell type. Using confocal microscopy, CD169(+) macrophages were located in the alveolar space/airway, defining them as alveolar macrophages. In contrast, CD169(-) macrophages were associated with airway/alveolar epithelium, consistent with interstitial-associated macrophages. We defined a flow cytometry panel in human BAL and lung tissue that allows identification of multiple immune cell types and delineates alveolar from interstitial-associated macrophages. This study has important implications for defining myeloid cells in human lung samples. PMID- 26267150 TI - Selective and Regenerative Carbon Dioxide Capture by Highly Polarizing Porous Carbon Nitride. AB - Energy-efficient CO2 capture is a stringent demand for green and sustainable energy supply. Strong adsorption is desirable for high capacity and selective capture at ambient conditions but unfavorable for regeneration of adsorbents by a simple pressure control process. Here we present highly regenerative and selective CO2 capture by carbon nitride functionalized porous reduced graphene oxide aerogel surface. The resultant structure demonstrates large CO2 adsorption capacity at ambient conditions (0.43 mmol.g(-1)) and high CO2 selectivity against N2 yet retains regenerability to desorb 98% CO2 by simple pressure swing. First principles thermodynamics calculations revealed that microporous edges of graphitic carbon nitride offer the optimal CO2 adsorption by induced dipole interaction and allows excellent CO2 selectivity as well as facile regenerability. This work identifies a customized route to reversible gas capture using metal-free, two-dimensional carbonaceous materials, which can be extended to other useful applications. PMID- 26267152 TI - Coverage Dependence of Methanol Dissociation on TiO2(110). AB - Although the photochemistry of methanol on TiO2(110) has been widely investigated as a prototypical model of the photocatalytic reaction of organic molecules, the most fundamental question of the adsorption state of methanol on TiO2(110) is still unclear. We have investigated the adsorption of methanol on TiO2(110) using sum frequency generation vibrational spectroscopy (SFG-VS) and density functional theory (DFT) calculations. The SFG results indicate the dissociation of methanol is highly dependent on the coverage. The DFT calculations suggest that the methanol prefers the partially dissociated structure at low coverage, whereas the second layer methanol, which is hydrogen-bonded to the bridge-bonded oxygen site, largely blocks the dissociation of the first layer methanol. Our results not only resolves a long-standing debate regarding the adsorption state of methanol on TiO2(110) but also provides a detailed insight into the adsorption structure and sheds light on the photochemistry on this surface at the molecular level. PMID- 26267153 TI - [Cr(ddpd)2](3+): A Molecular, Water-Soluble, Highly NIR-Emissive Ruby Analogue. AB - Bright, long-lived emission from first-row transition-metal complexes is very challenging to achieve. Herein, we present a new strategy relying on the rational tuning of energy levels. With the aid of the large N-Cr-N bite angle of the tridentate ligand ddpd (N,N'-dimethyl-N,N'-dipyridine-2-ylpyridine-2,6-diamine) and its strong sigma-donating capabilities, a very large ligand-field splitting could be introduced in the chromium(III) complex [Cr(ddpd)2](3+), that shifts the deactivating and photoreactive (4)T2 state well above the emitting (2)E state. Prevention of back-intersystem crossing from the (2)E to the (4)T2 state enables exceptionally high near-infrared phosphorescence quantum yields and lifetimes for this 3d metal complex. The complex [Cr(ddpd)2](BF4)3 is highly water-soluble and very stable towards thermal and photo-induced substitution reactions and can be used for fluorescence intensity- and lifetime-based oxygen sensing in the NIR. PMID- 26267151 TI - Association of Thalamic Dysconnectivity and Conversion to Psychosis in Youth and Young Adults at Elevated Clinical Risk. AB - IMPORTANCE: Severe neuropsychiatric conditions, such as schizophrenia, affect distributed neural computations. One candidate system profoundly altered in chronic schizophrenia involves the thalamocortical networks. It is widely acknowledged that schizophrenia is a neurodevelopmental disorder that likely affects the brain before onset of clinical symptoms. However, no investigation has tested whether thalamocortical connectivity is altered in individuals at risk for psychosis or whether this pattern is more severe in individuals who later develop full-blown illness. OBJECTIVES: To determine whether baseline thalamocortical connectivity differs between individuals at clinical high risk for psychosis and healthy controls, whether this pattern is more severe in those who later convert to full-blown illness, and whether magnitude of thalamocortical dysconnectivity is associated with baseline prodromal symptom severity. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter, 2-year follow-up, case-control study, we examined 397 participants aged 12-35 years of age (243 individuals at clinical high risk of psychosis, of whom 21 converted to full-blown illness, and 154 healthy controls). The baseline scan dates were January 15, 2010, to April 30, 2012. MAIN OUTCOMES AND MEASURES: Whole-brain thalamic functional connectivity maps were generated using individuals' anatomically defined thalamic seeds, measured using resting-state functional connectivity magnetic resonance imaging. RESULTS: Using baseline magnetic resonance images, we identified thalamocortical dysconnectivity in the 243 individuals at clinical high risk for psychosis, which was particularly pronounced in the 21 participants who converted to full-blown illness. The pattern involved widespread hypoconnectivity between the thalamus and prefrontal and cerebellar areas, which was more prominent in those who converted to full-blown illness (t(173) = 3.77, P < .001, Hedge g = 0.88). Conversely, there was marked thalamic hyperconnectivity with sensory motor areas, again most pronounced in those who converted to full-blown illness (t(173) = 2.85, P < .001, Hedge g = 0.66). Both patterns were significantly correlated with concurrent prodromal symptom severity (r = 0.27, P < 3.6 * 10(-8), Spearman rho = 0.27, P < 4.75 * 10(-5), 2-tailed). CONCLUSIONS AND RELEVANCE: Thalamic dysconnectivity, resembling that seen in schizophrenia, was evident in individuals at clinical high risk for psychosis and more prominently in those who later converted to psychosis. Dysconnectivity correlated with symptom severity, supporting the idea that thalamic connectivity may have prognostic implications for risk of conversion to full-blown illness. PMID- 26267156 TI - Virus genotypes and responses of serum-specific antibodies in children with primary mumps and mumps reinfection. AB - BACKGROUND: Research on children with mumps reinfection after natural infection is limited; there are currently no studies on virus-specific antibody responses in paired sera or genotyping of isolated viruses. METHODS: This study included 281 children (147 boys and 134 girls, age: 1.2-15.9 y) with primary mumps (240), mumps reinfection after natural infection (9), mumps after previous vaccination (26), and vaccine-associated mumps (6). We measured mumps-specific serum antibodies and analyzed isolated virus genes. RESULTS: During acute illness, series-specific IgM and IgG titers exceeded cutoff values in 240 and 232 children with primary mumps, respectively. During convalescence, IgM antibodies were positive in seven and negative in two of nine children with mumps reinfection occurring after natural infection; among 26 previously vaccinated children, 13 were positive and 13 negative. Mumps viruses were isolated from viral cultures from 42 of the 51 children. Except for 6 vaccine-associated cases, all remaining 36 cases of isolated mumps virus were identified as genotype G. CONCLUSION: These results suggest that measurement of IgM antibody on any day of acute illness may be indicative of primary mumps but may be inconsistent for diagnosing mumps reinfection after natural infection or previous vaccination. PMID- 26267157 TI - Chromatographic Analysis of Inks for Forensic Science Applications. AB - This article reviews the use of chromatography for the separation and comparison of ink components. Thin layer chromatography (TLC) is the standard chromatographic procedure presently employed for the comparison of inks. Thin layer chromatography systems are described for the separation of different types of ink. The greater sensitivity and resolution offered by high performance liquid chromatography (HPLC) make it an attractive alternative to TLC for ink analysis, and recent work in this field is also outlined. Both techniques have been used for the measurement of changes occurring in the composition of inks with time, as a means of determining the age of an ink. Related analytical techniques, recent research, and future trends in ink analysis are also described. PMID- 26267155 TI - Comparison of biomarkers for systemic juvenile idiopathic arthritis. AB - BACKGROUND: Differentiation of systemic juvenile idiopathic arthritis (SJIA) fever from other childhood fevers is often delayed due to the lack of reliable, specific biomarkers. We hypothesized that PD-L1 expression is dysregulated in SJIA monocytes and compared it to other candidate SJIA biomarkers. METHODS: This pilot study enrolled children with fever without source and compared PD-L1 expression on myeloid cells to C-reactive protein, erythrocyte sedimentation rate, leukocyte counts, S100A12, S100A8, S100A9, calprotectin, and procalcitonin. Logistic regression models were fit to test SJIA diagnosis with each marker used as an independent predictor. Receiver operating characteristic curves and area under curve were calculated. Gene expression profiling on a subset of samples was performed. RESULTS: Twenty subjects (10 active SJIA, 10 febrile non-SJIA) were enrolled. S100 proteins were significantly elevated in SJIA with >80% sensitivity and >90% specificity. PD-L1 expression was significantly lower in SJIA. Other markers were not specific for SJIA. On exploratory gene analysis, 106 genes were significant for SJIA association, and several of these are associated with immune response pathways. CONCLUSION: In this small cohort, S100 proteins were specific diagnostic biomarkers for SJIA in children with fever. Decreased PD-L1 surface expression on circulating myeloid cells in SJIA suggests possible mechanism for loss of peripheral immune regulation. PMID- 26267154 TI - The role of Th17 and Treg responses in the pathogenesis of RSV infection. AB - The respiratory syncytial virus (RSV) represents the leading cause of viral bronchiolitis and pneumonia in children worldwide and is associated with high morbidity, hospitalization rate, and significant mortality rates. The immune response elicited by RSV is one of the main factors contributing to the pathogenesis of the disease. Two subsets of the cellular immune response, the T helper 17 cell (Th17) and the regulatory T-cell (Treg), and more particularly the balance between these two subsets, might play a significant role in the pathogenesis of the RSV infection. The developmental pathways of Th17 and Treg cells are closely and reciprocally interconnected and plasticity has been demonstrated from Treg toward Th17. During an RSV infection, the functions of both subsets are opposed to one another regarding viral clearance and clinical severity. Th17 and Treg cells offer a promising new view on the pathogenesis of an RSV infection and deserve further exploration. PMID- 26267158 TI - Forensic Identification of Explosives by Mass Spectrometry and Allied Techniques. AB - A review of the reported methods for the recovery of fingerprints from the skin of crime victims along with the efficacy of those methods is presented. The fundamental problems of retrieval of latent fingerprints from the skin are discussed together with the methods reported in the literature, which include electronography, iron powder-Dakty foil, iodine-silver plate transfer, Kromekote(r) lift, and laser detection, along with several less frequently used techniques. The limited successes achieved with these reported methods during actual casework are discussed; they are limited because they are often found to refer only to idealized research conditions. At present, the use of high-powered light sources such as lasers seems to be the only technique that may be useful for revealing fingerprints on skin when investigating a case. PMID- 26267159 TI - Forensic Analysis of Lubricants. AB - Lubricants are found everywhere as a matter of course, and thus would also likely be found at the scene of a crime. Many fields of applications for lubricants exist and numerous formulations can be used within a single field. In addition, the composition of a lubricant changes significantly during its use. These facts are an illustration that lubricants, especially those that have been used, will have features that may possess high evidential value. Most studies on lubricants deal with wear monitoring, monitoring of the degradation of lubricants, and chemical analysis of the base oil and additives. The methods used require sample sizes in the range of 0.5 g and can give an indication of the brand and its application. In contrast, the studies dealing with forensic problems utilize spectroscopic methods that require sample sizes in the microgram range, and can only compare samples. Their main drawback is that the sample matrix may have an adverse effect on the analysis. Analyses using a combination of chromatographic and spectroscopic methods for the detection of special compound classes require more sample but are not as affected by the matrix. Using the methods reviewed here, the forensic scientist may be able to identify the brand and application if the sample size exceeds 0.5 g or may compare samples if the size is very low. PMID- 26267160 TI - Sample Differentiation: Cocaine Example. AB - Since the analyses of drug samples in crime laboratories are often associated with investigations, potential differentiations of test samples are frequently requested and explored. Cocaine sample differentiation requires the determination of synthetic or natural origin. Synthetic samples are characterized by the presence of optical isomers, certain diastereoisomers and other by-products, and chemical residues used in synthesis. Samples derived from a natural origin (coca leaves) are characterized by the presence of certain natural products or their derivatives that are carried through the overall process and by residual chemicals reflecting the treatment procedures. Various approaches and analytical data available in the literature concerning the differentiation of cocaine samples are reviewed. Each sample must carry its own "signature"; however, true sample "individualization" cannot be accomplished using the technologies commonly available and used in crime laboratories, and is not usually needed. Alternatively, "classifying" cocaine samples in certain categories or groups can be accomplished routinely and often provides adequate information for investigatory purposes. PMID- 26267161 TI - Solid Phase Extraction of Abused Drugs. AB - The current standard for acceptable practice in forensic urine drug testing, as reflected in both National Institute for Drug Abuse (NIDA) and military guidelines, requires an initial immunoassay followed by gas chromatography/mass spectrometry (GC/MS) confirmation. The GC/MS confirmatory procedures mandate extraction of the drug from the urine matrix, followed in most cases by chemical derivatization, prior to injection into the gas chromatograph. Classically, the extraction step has been accomplished using liquid-liquid techniques, but in recent years, the use of solid phase chromatographic techniques has become increasingly popular. Numerous companies now market solid phase columns that are designed specifically for extraction of drugs, some of them containing as many as three different components for extracting acidic, basic, and neutral drugs. A survey of NIDA laboratories, conducted specifically for this review article, revealed that 40 to 50% of the extraction procedures currently performed involved the use of solid phase cartridges. This article reviews chromatographic separation techniques in general, specific products that are currently available on the market, the performance of those products, and examines the results of the survey of NIDA-certified laboratories. PMID- 26267162 TI - Publication rate of studies presented at veterinary anaesthesia specialty meetings during the years 2003-2008. AB - OBJECTIVE: To assess publication rates, factors predicting publication, and discrepancies between conference abstracts and subsequent full-text publications of abstracts from the veterinary meetings of the American College of Veterinary Anesthesiologists and the Association of Veterinary Anaesthetists from 2003 to 2008. STUDY DESIGN: Retrospective cohort study. METHODS: A total of 607 abstracts were identified and a database search (Scopus, PubMed, CAB) was conducted to identify matching publications. Authors of nonmatching abstracts were contacted to participate in a confidential online survey. Risk ratios were used to assess factors predicting publication and these were tested for significance (p < 0.05) using Fisher's exact test. RESULTS: The overall publication rate was 63.3% and the mean (+/- SD) time to publication was 25 +/- 19 months. Factors significantly associated with subsequent full publication (i.e. publication of a full manuscript in a peer-reviewed journal) were continent of origin (North America), study design (experimental studies), specialty (analgesia) and the presence of a source of funding. The principal reasons why studies remained unpublished were lack of time and responsibility lying with co-authors. Minor changes compared with the original abstract were found in 71.6% of all publications. Major changes were noted in 34.6% and the outcome of the study changed in 7.6%. CONCLUSIONS AND CLINICAL RELEVANCE: These data suggest that some of the abstracts reported preliminary findings. Therefore, caution is warranted when quoting abstracts as references in scientific publications. To date, major veterinary journals have not issued recommendations in their author guidelines addressing the use of abstracts as a reference. The authors propose the inclusion of such a statement in author guidelines. PMID- 26267163 TI - Inhibitory effects of Lactobacillus fermentum on microbial growth and biofilm formation. AB - Beneficial effects of Lactobacilli have been reported, and lactic bacteria are employed for conservation of foods. Therefore, the effects of a Lactobacillus fermentum strain were analyzed regarding inhibitory effects on staphylococci, Candida albicans and enterotoxigenic enterobacteria by transmission electron microscopy (TEM). TEM of bacterial biofilms was performed using cocultures of bacteriocin-producing L. fermentum 97 with different enterotoxigenic strains: Staphylococcus epidermidis expressing the ica gene responsible for biofilm formation, Staphylococcus aureus producing enterotoxin type A, Citrobacter freundii, Enterobacter cloaceae, Klebsiella oxytoca, Proteus mirabilis producing thermolabile and thermostable enterotoxins determined by elt or est genes, and Candida albicans. L. fermentum 97 changed morphological features and suppressed biofilm formation of staphylococci, enterotoxigenic enterobacteria and Candida albicans; a marked transition to resting states, a degradation of the cell walls and cytoplasm, and a disruption of mature bacterial biofilms were observed, the latter indicating efficiency even in the phase of higher cell density. PMID- 26267164 TI - Impact of exopolysaccharide production on functional properties of some Lactobacillus salivarius strains. AB - The aim of this work was to characterize functional properties of Lactobacillus salivarius strains isolated from chicken feces. Detection of genes responsible for exopolysaccharide (EPS) production revealed that all strains harbored a dextransucrase gene, but p-gtf gene was only detected in strain E4. Analysis of EPS production levels showed significant alterations among strains tested. Biofilm formation was found to be medium composition dependant, and there was a negative correlation with biofilm formation and EPS production. Autoaggregation properties and coaggregation of L. salivarius strains with chicken pathogens were appeared to be specific at strain level. An increment in bacterial adhesion to chicken gut explants was observed in L. salivarius strains with the reduction in EPS production levels. This study showed that strain-specific properties can determine the functional properties of L. salivarius strains, and the interference of these properties might be crucial for final selection of these strains for technological purposes. PMID- 26267165 TI - Deciphering the reaction between a hydrated electron and a hydronium ion at elevated temperatures. AB - The formation of a H atom in liquid water from the reaction of a hydrated electron with a hydronium cation is a very challenging subject in chemical processes. Here picosecond pulse radiolysis measurements are performed at elevated temperatures, up to 350 degrees C, of acidic H2O and D2O solutions (up to 0.1 mol L(-1) HClO4) with the aim of investigating several issues related to this reaction. First, the red shift of the solvated electron absorption band in D2O with increasing temperature is found to be affected by the presence of D3O(+) in solution. The modified absorption spectra demonstrate the formation of a transient pair between D3O(+) and solvated electrons at elevated temperature (200 250 degrees C) when the concentration of D3O(+) is higher than 0.05 mol L(-1). For higher temperatures at 300 and 350 degrees C when the rate constant is almost diffusion controlled, the pair is no longer observable. Second, the presolvated electron in D2O is not scavenged up to 250 degrees C in solution containing 0.1 mol L(-1) D3O(+). Third, the decays in the picosecond range obtained under different conditions show that the rate constants are strongly affected by the temperature and by ionic strength. The model with an equation of log(k/k0) = 2A(I)(0.5)/1 + b(I)(0.5) gives a good fit of the experimental results by taking into account the variation of ionic strength, I, and, in particular, by considering the temperature dependence of the constant A. PMID- 26267166 TI - Unexpected Swelling of Stiff DNA in a Polydisperse Crowded Environment. AB - We investigate the conformations of DNA-like stiff chains, characterized by contour length (L) and persistence length (lp), in a variety of crowded environments containing monodisperse soft spherical (SS) and spherocylindrical (SC) particles, a mixture of SS and SC, and a milieu mimicking the composition of proteins in the Escherichia coli cytoplasm. The stiff chain, whose size modestly increases in SS crowders up to phi ~ 0.1, is considerably more compact at low volume fractions (phi <= 0.2) in monodisperse SC particles than in a medium containing SS particles. A 1:1 mixture of SS and SC crowders induces greater chain compaction than the pure SS or SC crowders at the same phi, with the effect being highly nonadditive. We also discover a counterintuitive result that the polydisperse crowding environment, mimicking the composition of a cell lysate, swells the DNA-like polymer, which is in stark contrast to the size reduction of flexible polymers in the same milieu. Trapping of the stiff chain in a fluctuating tube-like environment created by large-sized crowders explains the dramatic increase in size and persistence length of the stiff chain. In the polydisperse medium, mimicking the cellular environment, the size of the DNA (or related RNA) is determined by L/lp. At low L/lp, the size of the polymer is unaffected, whereas there is a dramatic swelling at an intermediate value of L/lp. We use these results to provide insights into recent experiments on crowding effects on RNA and also make testable predictions. PMID- 26267168 TI - Effects of the NFL's Amendments to the Free Kick Rule on Injuries during the 2010 and 2011 Seasons. AB - Recognizing the chronic health effects associated with playing football, the National Football League (NFL) has enacted policies and rules aimed at improving player health and safety. Prior to the 2011 season, amendments to the Free Kick rule were implemented, whereby the restraining line was moved from the 30- to the 35-yard line and all kicking team players other than the kicker were required to line up no more than 5 yards behind their restraining line. The objective of this analysis was to evaluate the effects of these rule changes on injury rates. Data for injuries occurring on special teams plays during the 2010 and 2011 NFL seasons were obtained from publically available NFL gamebooks and injury reports. Injury rates for kickoff plays across seasons were statistically compared using incidence rate ratios (RR) and 95% confidence intervals. To evaluate whether injury rate changes could be attributable to the rule amendments, comparisons were made with punt injury rates (presumably unaffected by the Free Kick rule changes) and distributions of potential confounders were assessed across seasons. Incidence of injuries occurring on kickoff plays fell from 2010 to 2011 (RR: 0.45, 95% CI: 0.28-0.73), although on kickoff plays where the ball was returned, this decrease became non-significant (RR: 0.67, 95% CI: 0.41-1.08). While the incidence of head injuries decreased by approximately 3-fold during kickoff plays, this change was not statistically significant (RR: 0.33, 95% CI: 0.09 1.21). No difference was observed in injury incidence during punts between the two seasons, and the distribution of confounding factors was largely uniform across seasons. The observed decrease in injuries occurring during kickoffs was likely directly attributable to the Free Kick rule amendments, principally from the increased frequency of touchbacks. The absence of a significant change in head injuries during kickoffs was unexpected, but may be attributable to small sample size. Despite the injury rate reductions, the rule changes likely had little effect on player safety during active gameplay. PMID- 26267167 TI - Interaction between lanthanide ions and Saccharomyces cerevisiae cells. AB - Lanthanides are a group of non-essential elements with important imaging and therapeutic applications. Although trivalent lanthanide ions (Ln3+) are used as potent blockers of Ca2+ channels, the systematic studies correlating Ln3+ accumulation and toxicity to Ca2+ channel blocking activity are scarce. In this study, we made use of the eukaryotic model Saccharomyces cerevisiae to investigate the correlation between Ln3+ accumulation, their toxicity and their capacity to block the exogenous stress-induced Ca2+ influx into the cytosol. It was found that the Ln3+ blocked the Ca2+ entry into the yeast cells only when present at concentration high enough to allow rapid binding to cell surface. At lower concentrations, Ln3+ were taken up by the cell, but Ca2+ blockage was no longer achieved. At 1 mM concentration, all ions from the Ln3+ series could block Ca2+ entry into cytosol with the exception of La3+, and to a lesser extent, Pr3+ and Nd3+. The plasma membrane Ca2+-channel Cch1/Mid1 contributed to La3+ and Gd3+ entry into the cells, with a significant preference for La3+. The results open the possibility to obtain cells loaded with controlled amounts and ratios of Ln3+. PMID- 26267169 TI - Imaging Charge Transfer State Excitations in Polymer/Fullerene Solar Cells with Time-Resolved Electrostatic Force Microscopy. AB - We demonstrate nanoscale imaging of charge transfer state photoexcitations in polymer/fullerene bulk heterojunction solar cells using time-resolved electrostatic force microscopy (trEFM). We compare local trEFM charging rates and external quantum efficiencies (EQE) for both above-gap and below-gap excitation of the model system poly[2-methoxy-5-(3',7'-dimethyloctyloxy)-1,4 phenylenevinylene] (MDMO-PPV) and [6,6]-phenyl C61 butyric acid methyl ester (PCBM). We show that the local trEFM charging rate correlates with device EQE for both above-gap and below-gap photoexcitation, demonstrating that EFM methods have sufficient sensitivity to detect the low EQEs associated with CT state formation, a result that could be useful for probing weak subgap excitations in nanostructured materials such as quantum dot and organometal halide perovskite solar cells. Further, we use trEFM to map spatial variations in EQE arising from subgap CT excitation in organic photovoltaics (OPVs) and find that the local distribution of photocurrent arising from these states is nearly identical to the spatial variation in EQE from above-gap singlet excitation. These results are consistent with recent work showing that both above-gap and below-gap excitation have similar internal quantum efficiency. PMID- 26267170 TI - Subpicosecond to Second Time-Scale Charge Carrier Kinetics in Hematite-Titania Nanocomposite Photoanodes. AB - Water splitting with hematite is negatively affected by poor intrinsic charge transport properties. However, they can be modified by forming heterojunctions to improve charge separation. For this purpose, charge dynamics of TiO2:alpha-Fe2O3 nanocomposite photoanodes are studied using transient absorption spectroscopy to monitor the evolution of photogenerated charge carriers as a function of applied bias voltage. The bias affects the charge carrier dynamics, leading to trapped electrons in the submillisecond time scale and an accumulation of holes with a lifetime of 0.4 +/- 0.1 s. By contrast, slower electron trapping and only few long-lived holes are observed in a bare hematite photoanode. The decay of the long-lived holes is 1 order of magnitude faster for the composite photoanodes than previously published for doped hematite, indicative of higher catalytic efficiency. These results illustrate the advantages of using composite materials to overcome poor charge carrier dynamics, leading to a 30-fold enhancement in photocurrent. PMID- 26267171 TI - Reactivity of Hydrated Electron in Finite Size System: Sodium Pickup on Mixed N2O Water Nanoparticles. AB - We investigate the reactivity of hydrated electron generated by alkali metal deposition on small water particles with nitrous oxide dopant by means of mass spectrometry and ab initio molecular dynamics simulations. The mixed nitrous oxide/water clusters were generated in a molecular beam and doped with Na atoms in a pickup experiment, and investigated by mass spectrometry using two different ionization schemes: an electron ionization (EI), and UV photoionization after the Na doping (NaPI). The NaPI is a soft-ionization nondestructive method, especially for water clusters provided that a hydrated electron es- is formed in the cluster. The missing signal for the doped clusters indicates that the hydrated electron is not present in the N2O containing clusters. The simulations reveal that the hydrated electron is formed, but it immediately reacts with N2O, forming first N2O- radical anion, later O-, and finally an OH* and OH- pair. PMID- 26267172 TI - Curvature-Induced Anomalous Enhancement in the Work Function of Nanostructures. AB - An analytical theory to estimate the electronic work function in curved geometries is formulated under Thomas-Fermi approximation. The work function is framed as the work against the electrostatic self-capacitive energy. The contribution of surface curvature is characterized by mean and Gaussian curvature (through multiple scattering expansion). The variation in work function of metal and semimetal nanostructures is shown as the consequence of surface radius of curvature comparable to electronic screening length. For ellipsoidal particles, the maximum value of work function is observed at the equator and poles for oblate and prolate particles, respectively, whereas triaxial ellipsoid shows nonuniform distribution of the work function over the surface. Similarly, theory predicts manifold increase in the work function for a particle with atomic scale roughness. Finally, the theory is validated with experimental data, and it is concluded that the work function of a nanoparticle can be tailored through its shape. PMID- 26267173 TI - Effect of Chromophore Potential Model on the Description of Exciton-Phonon Interactions. AB - System-bath interactions in nonadiabatic simulations are often depicted by first performing molecular dynamics calculations and then by evaluating excitation energies at the trajectory snapshots. Usually, molecular mechanics models and quantum chemical calculations are used in a mixed manner toward a trade-off between efficiency and accuracy. Here we investigate how this mixing scheme affects that depiction by using various potential energy surfaces (PESs) of coumarin-153 chromophore, with the help of interpolated PESs that can closely match the accuracies of quantum chemical calculations. We find that although spectral densities are computed only with second stage data the PES characteristics during the first sampling stage can still prevail in the densities, with limited influences on related reorganization energies. Our results suggest that using the mixed scheme can be acceptable when dynamics is mainly governed by the integrated effect of all phonon modes, but care must be taken for understanding detailed effects from individual modes. PMID- 26267174 TI - Microscopic Origin of the Hofmeister Effect in Gelation Kinetics of Colloidal Silica. AB - The gelation kinetics of silica nanoparticles is a central process in physical chemistry, yet it is not fully understood. Gelation times are measured to increase by over 4 orders of magnitude, simply changing the monovalent salt species from CsCl to LiCl. This striking effect has no microscopic explanation within current paradigms. The trend is consistent with the Hofmeister series, pointing to short-ranged solvation effects not included in the standard colloidal (DLVO) interaction potential. By implementing a simple form for short-range repulsion within a model that relates the gelation timescale to the colloidal interaction forces, we are able to explain the many orders of magnitude difference in the gelation times at fixed salt concentration. The model allows us to estimate the magnitude of the non-DLVO hydration forces, which dominate the interparticle interactions on the length scale of the hydrated ion diameter. This opens the possibility of finely tuning the gelation time scale of nanoparticles by just adjusting the background electrolyte species. PMID- 26267175 TI - Effects of Solute-Solvent Hydrogen Bonding on Nonaqueous Electrolyte Structure. AB - We investigate the source of Raman background signal commonly misidentified as fluorescence in nonaqueous electrolytes via a variety of spectroscopies (Raman, fluorescence, NMR) and find evidence of hydrogen-bonding interactions. This hydrogen bonding gives rise to broadband anharmonic vibrational modes and suggests that anions play an important and underappreciated role in the structure of nonaqueous electrolytes. Controlling electrolyte structure has important applications in advancing in operando spectroscopy measurements as well as understanding the stability of high concentration electrolytes for next generation electrochemical energy storage devices. PMID- 26267176 TI - Exploration of Metal Chloride Uptake for Improved Performance Characteristics of PbSe Quantum Dot Solar Cells. AB - We explored the uptake of metal chloride salts with +1 to +3 metals of Na(+), K(+), Zn(2+), Cd(2+), Sn(2+), Cu(2+), and In(3+) by PbSe QD solar cells. We also compared CdCl2 to Cd acetate and Cd nitrate treatments. PbSe QD solar cells fabricated with a CdCl2 treatment are stable for more than 270 days stored in air. We studied how temperature and immersion times affect optoelectronic properties and photovoltaic cell performance. Uptake of Cd(2+) and Zn(2+) increase open circuit voltage, whereas In(3+) and K(+) increase the photocurrent without influencing the spectral response or first exciton peak position. Using the most beneficial treatments we varied the bandgap of PbSe QD solar cells from 0.78 to 1.3 eV and find the improved VOC is more prevalent for lower bandgap QD solar cells. PMID- 26267177 TI - Science in the Age of Digital Networking. PMID- 26267178 TI - Density and Compressibility of Liquid Water and Ice from First-Principles Simulations with Hybrid Functionals. AB - We determined the equilibrium density and compressibility of water and ice from first-principles molecular dynamics simulations using gradient-corrected (PBE) and hybrid (PBE0) functionals. Both functionals predicted the density of ice to be larger than that of water, by 15 (PBE) and 35% (PBE0). The PBE0 functional yielded a lower density of both ice and water with respect to PBE, leading to better agreement with experiment for ice but not for liquid water. Approximate inclusion of dispersion interactions on computed molecular-dynamics trajectories led to a substantial improvement of the PBE0 results for the density of liquid water, which, however, resulted to be slightly lower than that of ice. PMID- 26267179 TI - Probing Interfacial Water on Nanodiamonds in Colloidal Dispersion. AB - The structure of interfacial water layers around nanoparticles dispersed in an aqueous environment may have a significant impact on their reactivity and on their interaction with biological species. Using transmission soft X-ray absorption spectroscopy in liquid, we demonstrate that the unoccupied electronic states of oxygen atoms from water molecules in aqueous colloidal dispersions of nanodiamonds have a different signature than bulk water. X-ray absorption spectroscopy can thus probe interfacial water molecules in colloidal dispersions. The impacts of nanodiamond surface chemistry and concentration on interfacial water electronic signature are discussed. PMID- 26267180 TI - Infrared Spectroscopic Study of Vibrational Modes in Methylammonium Lead Halide Perovskites. AB - The organic cation and its interplay with the inorganic lattice underlie the exceptional optoelectronic properties of organo-metallic halide perovskites. Herein we report high-quality infrared spectroscopic measurements of methylammonium lead halide perovskite (CH3NH3Pb(I/Br/Cl)3) films and single crystals at room temperature, from which the dielectric function in the investigated spectral range is derived. Comparison with electronic structure calculations in vacuum of the free methylammonium cation allows for a detailed peak assignment. We analyze the shifts of the vibrational peak positions between the different halides and infer the extent of interaction between organic moiety and the surrounding inorganic cage. The positions of the NH3(+) stretching vibrations point to significant hydrogen bonding between the methylammonium and the halides for all three perovskites. PMID- 26267181 TI - Exciton Mobility in Organic Photovoltaic Heterojunctions from Femtosecond Stimulated Raman. AB - Exciton mobility is crucial to organic photovoltaic (OPV) efficiency, but accurate, quantitative measures and therefore precise understanding of this process are currently lacking. Here, we exploit the unique capabilities of femtosecond stimulated Raman spectroscopy (FSRS) to disentangle the signatures of the bulk and interfacial donor response in a bulk heterojunction composed of poly[2-methoxy-5-(3',7'-dimethyloctyloxy)-1,4-phenylenevinylene] (MDMO-PPV) and phenyl-C61-butyric acid methyl ester (PCBM). Surprisingly, we find that donor excitons are very mobile for the first ~300 fs following excitation (before thermalization) even though their overall lifetime is significantly longer (170 ps). A sharp decrease in mobility occurs after the system relaxes out of the Franck-Condon (FC) region. From this observation we predict that any polymer lacking a significant resonance Raman effect and fluorescence Stokes shift, indicating slow FC relaxation and small reorganization energy, will make an efficient OPV material. PMID- 26267182 TI - Differential Microscopic Mobility of Components within a Deep Eutectic Solvent. AB - From macroscopic measurements of deep eutectic solvents such as glyceline (1:2 molar ratio of choline chloride to glycerol), the long-range translational diffusion of the larger cation (choline) is known to be slower compared to that of the smaller hydrogen bond donor (glycerol). However, when the diffusion dynamics are analyzed on the subnanometer length scale, we find that the displacements associated with the localized diffusive motions are actually larger for choline. This counterintuitive diffusive behavior can be understood as follows. The localized diffusive motions confined in the transient cage of neighbor particles, which precede the cage-breaking long-range diffusion jumps, are more spatially constrained for glycerol than for choline because of the stronger hydrogen bonds the former makes with chloride anions. The implications of such differential localized mobility of the constituents should be especially important for applications where deep eutectic solvents are confined on the nanometer length scale and their long-range translational diffusion is strongly inhibited (e.g., within microporous media). PMID- 26267183 TI - Pathways for H2 Activation on (Ni)-MoS2 Catalysts. AB - The activation of H2 and H2S on (Ni)MoS2/Al2O3 leads to the formation of SH groups with acid character able to protonate 2,6-dimethylpyridine. The variation in concentrations of SH groups induced by H2 and H2S adsorption shows that both molecules dissociate on coordinatively unsaturated cations and neighboring S(2-). In the studied materials, one sulfur vacancy and four SH groups per 10 metal atoms exist at the active edges of MoS2 under the conditions studied. H2-D2 exchange studies show that Ni increases the concentration of active surface hydrogen by up to 30% at the optimum Ni loading, by increasing the concentration of H2 and H2S chemisorption sites. PMID- 26267184 TI - Thermal Recovery of Colloidal Quantum Dot Ensembles Following Photoinduced Dimming. AB - Colloidal CdSe quantum dot (QD) core ensembles were photodimmed and allowed to recover in the dark using ambient thermal energy at a range of temperatures. Nonlinear thermal recovery is well described by a stretched exponential function, and further analysis yields an underlying probability distribution of rate constants. Casting the rate constants as a collection of first-order activated processes provides an activation barrier probability distribution with significant density at room-temperature thermal energy that peaks at 200 meV before decaying to zero. This treatment for the recovery transition intuitively describes the distributed kinetics observed and complements commonly proposed blinking mechanisms. PMID- 26267185 TI - Family of Oxygen-Oxygen Radial Distribution Functions for Water. AB - In a typical X-ray diffraction experiment, the elastically scattered intensity, I(Q), is the experimental observable. I(Q) contains contributions from both intramolecular as well as intermolecular correlations embodied in the scattering factors, HOO(Q) and HOH(Q), with negligible contributions from HHH(Q). Thus, to accurately define the oxygen-oxygen radial distribution function, gOO(r), a model of the electron density is required to accurately weigh the HOO(Q) component relative to the intramolecular and oxygen-hydrogen correlations from the total intensity observable. In this work, we carefully define the electron density model and its underlying assumptions and more explicitly utilize two restraints on the allowable gOO(r) functions, which must conform to both very low experimental errors at high Q and the need to satisfy the isothermal compressibility at low Q. Although highly restrained by these conditions, the underdetermined nature of the problem is such that we present a family of gOO(r) values that provide equally good agreement with the high-Q intensity and compressibility restraints and with physically correct behavior at small r. PMID- 26267186 TI - Charge and Nuclear Dynamics Induced by Deep Inner-Shell Multiphoton Ionization of CH3I Molecules by Intense X-ray Free-Electron Laser Pulses. AB - In recent years, free-electron lasers operating in the true X-ray regime have opened up access to the femtosecond-scale dynamics induced by deep inner-shell ionization. We have investigated charge creation and transfer dynamics in the context of molecular Coulomb explosion of a single molecule, exposed to sequential deep inner-shell ionization within an ultrashort (10 fs) X-ray pulse. The target molecule was CH3I, methane sensitized to X-rays by halogenization with a heavy element, iodine. Time-of-flight ion spectroscopy and coincident ion analysis was employed to investigate, via the properties of the atomic fragments, single-molecule charge states of up to +22. Experimental findings have been compared with a parametric model of simultaneous Coulomb explosion and charge transfer in the molecule. The study demonstrates that including realistic charge dynamics is imperative when molecular Coulomb explosion experiments using short pulse facilities are performed. PMID- 26267187 TI - Quantum Chemical Insight into the LiF Interlayer Effects in Organic Electronics: Reactions between Al Atom and LiF Clusters. AB - It is well known that the aluminum cathode performs dramatically better when a thin lithium fluoride (LiF) layer inserted in organic electronic devices. The doping effect induced by the librated Li atom via the chemical reactions producing AlF3 as byproduct was previously proposed as one of possible mechanisms. However, the underlying mechanism discussion is quite complicated and not fully understood so far, although the LiF interlayer is widely used. In this paper, we perform theoretical calculations to consider the reactions between an aluminum atom and distinct LiF clusters. The reaction pathways of the Al-(LiF)n (n = 2, 4, 16) systems were discovered and the energetics were theoretically evaluated. The release of Li atom and the formation of AlF3 were found in two different chemical reaction routes. The undissociated Al-(LiF)n systems have chances to change to some structures with loosely bound electrons. Our findings about the interacted Al-(LiF)n systems reveal new insights into the LiF interlayer effects in organic electronics applications. PMID- 26267188 TI - Highly Anisotropic Dirac Fermions in Square Graphynes. AB - We predict a family of 2D carbon (C) allotropes, square graphynes (S-graphynes) that exhibit highly anisotropic Dirac fermions, using first-principle calculations within density functional theory. They have a square unit-cell containing two sizes of square C rings. The equal-energy contour of their 3D band structure shows a crescent shape, and the Dirac crescent has varying Fermi velocities from 0.6 * 10(5) to 7.2 * 10(5) m/s along different k directions. Near the Fermi level, the Dirac crescent can be nicely expressed by an extended 2D Dirac model Hamiltonian. Furthermore, tight-binding band fitting reveals that the Dirac crescent originates from the next-nearest-neighbor interactions between C atoms. S-graphynes may be used to build new 2D electronic devices taking advantages of their highly directional charge transport. PMID- 26267189 TI - All-Atom Molecular Dynamics Simulation of Protein Translocation through an alpha Hemolysin Nanopore. AB - Nanopore sensing is attracting the attention of a large and varied scientific community. One of the main issues in nanopore sensing is how to associate the measured current signals to specific features of the molecule under investigation. This is particularly relevant when the translocating molecule is a protein and the pore is sufficiently narrow to necessarily involve unfolding of the translocating protein. Recent experimental results characterized the cotranslocational unfolding of Thioredoxin (Trx) passing through an alpha hemolisin pore, providing evidence for the existence of a multistep process. In this study we report the results of all-atom molecular dynamics simulations of the same system. Our data indicate that Trx translocation involves two main barriers. The first one is an unfolding barrier associated with a translocation intermediate where the N-terminal region of Trx is stuck at the pore entrance in a conformation that strongly resembles the native one. After the abrupt unfolding of the N-terminal region, the Trx enters the alpha-hemolisin vestibule. During this stage, the constriction is occupied not only by the translocating residue but also by a hairpin-like structure forming a tangle in the constriction. The second barrier is associated with the disentangling of this region. PMID- 26267191 TI - Transformation Chemistry of Gold Nanoclusters: From One Stable Size to Another. AB - Controlling nanoparticles with atomic precision has long been a major dream of nanochemists. This dream has first been realized in the case of gold nanoparticles. We previously discussed a size-focusing methodology for the syntheses of atomically precise gold nanoclusters protected by thiolate ligands (referred to as Aun(SR)m, where n and m represent the exact numbers of gold atoms and surface ligands). This methodology led to molecularly pure nanoclusters such as Au25(SR)18, Au38(SR)24, Au144(SR)60, and many others in recent work. In this Perspective article, we shall further discuss a new methodology for controlling the size and structure of nanoclusters through ligand-exchange-induced transformation of Aun(SR)m nanoclusters. Notable examples include the transformations of Au25(SR)18 to Au28(SR')20, Au38(SR)24 to Au36(SR')24, and Au144(SR)60 to Au133(SR')52. Total structures of the new nanoclusters have also been attained. The transformation processes are remarkable and resemble the organic transformation chemistry. We have also achieved mechanistic understanding on the transformation process, and a disproportionation mechanism has been for the first time identified. This new methodology (i.e., ligand-exchange-induced size/structure transformation, LEIST for short) has not only demonstrated the important role of thiolate ligand in the transformation chemistry of clusters but also paved the way for creating an expanded "library" of Aun(SR)m nanoclusters for exploration of their magic sizes, structures, properties, and applications. PMID- 26267190 TI - Exciton Binding Energy and the Nature of Emissive States in Organometal Halide Perovskites. AB - Characteristics of nanoscale materials are often different from the corresponding bulk properties providing new, sometimes unexpected, opportunities for applications. Here we investigate the properties of 8 nm colloidal nanoparticles of MAPbBr3 perovskites and contrast them to the ones of large microcrystallites representing a bulk. X-ray spectroscopies provide an exciton binding energy of 0.32 +/- 0.10 eV in the nanoparticles. This is 5 times higher than the value of bulk crystals (0.084 +/- 0.010 eV), and readily explains the high fluorescence quantum yield in nanoparticles. In the bulk, at high excitation concentrations, the fluorescence intensity has quadratic behavior following the Saha-Langmuir model due to the nongeminate recombination of charges forming the emissive exciton states. In the nanoparticles, a linear dependence is observed since the excitation concentration per particle is significantly less than one. Even the bulk shows linear emission intensity dependence at lower excitation concentrations. In this case, the average excitation spacing becomes larger than the carrier diffusion length suppressing the nongeminate recombination. From these considerations we obtain the charge carrier diffusion length in MAPbBr3 of 100 nm. PMID- 26267192 TI - Pulling and Stretching a Molecular Wire to Tune its Conductance. AB - A scanning tunnelling microscope is used to pull a polythiophene wire from a Au(111) surface while measuring the current traversing the junction. Abrupt current increases measured during the lifting procedure are associated with the detachment of molecular subunits, in apparent contradiction with the expected exponential decrease of the conductance with wire length. Ab initio simulations reproduce the experimental data and demonstrate that this unexpected behavior is due to release of mechanical stress in the wire, paving the way to mechanically gated single-molecule electronic devices. PMID- 26267193 TI - Coherent Nuclear Wave Packets in Q States by Ultrafast Internal Conversions in Free Base Tetraphenylporphyrin. AB - Persistence of vibrational coherence in electronic transition has been noted especially in biochemical systems. Here, we report the dynamics between electronic excited states in free base tetraphenylporphyrin (H2TPP) by time resolved fluorescence with high time resolution. Following the photoexcitation of the B state, ultrafast internal conversion occurs to the Qx state directly as well as via the Qy state. Unique and distinct coherent nuclear wave packet motions in the Qx and Qy states are observed through the modulation of the fluorescence intensity in time. The instant, serial internal conversions from the B to the Qy and Qx states generate the coherent wave packets. Theory and experiment show that the observed vibrational modes involve the out-of-plane vibrations of the porphyrin ring that are strongly coupled to the internal conversion of H2TPP. PMID- 26267194 TI - Fostered Thermomagnetic Stabilities and Boosted Mechanical Reliability Related to High Trapped Field in Composite Bulk YBa2Cu3O(7-delta) Cryomagnets. AB - In the quest of YBa2Cu3O(7-delta) (Y123) bulk superconductors providing strong magnetic fields without failure, it is of paramount importance to achieve high thermal stabilities to safeguard the magnetic energy inside them during the trapping-field process, and sufficient mechanical reliability to withstand the stresses derived from the Lorenz force. Herein, we experimentally demonstrate a temperature rise induced by dissipative flux motion inside an Y123 thin-wall superconductor, and a significant thermal exchange in a composite bulk Y123 cryomagnet realized by embedding this superconductor with high thermal conductivity metal network. It resulted in stimulating the maximum trapped field Bm, which reached 6.46 T on 15.9 mm-diameter single disk superconductor after magnetization by field cooling to 17 K under 7 T, leading to an improvement of 18% compared to the thin-wall superconductor. The composite cryomagnet particularly revealed the potential to trap stronger fields if larger magnetic activation is available. By virtue of the pore-free and crack-free microstructure of this cryomagnet, its strength sigmaR was estimated to be 363 MPa, the largest one obtained so far for Y123 bulk superconductors, thus suggesting a striking mechanical reliability that seems to be sufficient to sustain stresses derived from trapped fields stronger than any values hitherto reported. PMID- 26267195 TI - Quenching of Charge Transfer in Nitrobenzene Induced by Vibrational Motion. AB - Although nitrobenzene is the smallest nitro-aromatic molecule, the nature of its electronic structure is still unclear. Most notably, the lowest-energy absorption band was assessed in numerous studies providing conflicting results regarding its charge-transfer character. In this study, we employ a combination of molecular dynamics and quantum chemical methods to disentangle the nature of the lowest energy absorption band of nitrobenzene. Surprisingly, the charge-transfer transition from the benzene moiety to the nitro group is found to be quenched by a flow of charge into the opposite direction induced by vibrational motion. Beyond clarifying the charge-transfer character of nitrobenzene, we show that the widely used approach of analyzing the ground-state minimum-energy geometry provides completely wrong conclusions. PMID- 26267196 TI - Ice Nucleation Properties of Oxidized Carbon Nanomaterials. AB - Heterogeneous ice nucleation is an important process in many fields, particularly atmospheric science, but is still poorly understood. All known inorganic ice nucleating particles are relatively large in size and tend to be hydrophilic. Hence it is not obvious that carbon nanomaterials should nucleate ice. However, in this paper we show that four different readily water-dispersible carbon nanomaterials are capable of nucleating ice. The tested materials were carboxylated graphene nanoflakes, graphene oxide, oxidized single walled carbon nanotubes and oxidized multiwalled carbon nanotubes. The carboxylated graphene nanoflakes have a diameter of ~30 nm and are among the smallest entities observed so far to nucleate ice. Overall, carbon nanotubes were found to nucleate ice more efficiently than flat graphene species, and less oxidized materials nucleated ice more efficiently than more oxidized species. These well-defined carbon nanomaterials may pave the way to bridging the gap between experimental and computational studies of ice nucleation. PMID- 26267197 TI - Impact of Space-Charge Layers on Sudden Death in Li/O2 Batteries. AB - The performance of Li/O2 batteries is thought to be limited by charge transport through the solid Li2O2 discharge product. Prior studies suggest that electron tunneling is the main transport mechanism through thin, compact Li2O2 deposits. The present study employs a new continuum transport model to explore an alternative scenario, in which charge transport is mediated by polaron hopping. Unlike earlier models, which assume a uniform carrier concentration or local electroneutrality, the possibility of nonuniform space charge is accounted for at the Li2O2/electrolyte and Li2O2/electrode interfaces, providing a more realistic picture of transport in Li2O2 films. The temperature and current-density dependences of the discharge curves predicted by the model are in good agreement with flat-electrode experiments over a wide range of rates, supporting the hypothesis that polaron hopping contributes significantly to charge transport. Exercising the model suggests that this mechanism could explain the observed enhancement in cell performance at elevated temperature and that performance could be further improved by tuning the interfacial orientation of Li2O2 crystallites. PMID- 26267198 TI - Tuning Properties in Silver Clusters. AB - The properties of Ag nanoclusters are not as well understood as those of their more precious Au cousins. However, a recent surge in the exploration of strategies to tune the physicochemical characteristics of Ag clusters addresses this imbalance, leading to new insights into their optical, luminescence, crystal habit, metal-core, ligand-shell, and environmental properties. In this Perspective, we provide an overview of the latest strategies along with a brief introduction of the theoretical framework necessary to understand the properties of silver nanoclusters and the basis for their tuning. The advances in cluster research and the future prospects presented in this Perspective will eventually guide the next large systematic study of nanoclusters, resulting in a single collection of data similar to the periodic table of elements. PMID- 26267199 TI - Formation of Positively Charged Liquid Helium Clusters in Supercritical Helium and their Solidification upon Compression. AB - Positively charged ions were produced in supercritical helium at temperatures from 6 to 10 K and up to 2 MPa using a corona discharge. Their mobility was measured via current-voltage curves, and the hydrodynamic radius was derived using Stokes law. An initial increase and subsequent decrease of hydrodynamic radius was observed and interpreted in terms of growth, compression and solidification of ion clusters. The mobility was modeled using a van der Waals type thermodynamic state equation for the ion-in-helium mixed system and a temperature-dependent Millikan-Cunningham factor, describing experimental data both in the Knudsen and the Stokes flow region. Regions of maximum hydrodynamic radius and large compressibility were interpreted as boiling points. These points were modeled over a large range of pressures and found to match the Frenkel line of pure helium up to 0.7 MPa, reflecting similarity of density fluctuations in pure supercritical helium and gas-liquid phase transitions of ionic helium clusters. PMID- 26267200 TI - Spatial Localization of Excitons and Charge Carriers in Hybrid Perovskite Thin Films. AB - The fundamental photophysics underlying the remarkably high-power conversion efficiency of organic-inorganic hybrid perovskite-based solar cells has been increasingly studied using complementary spectroscopic techniques. However, the spatially heterogeneous polycrystalline morphology of the photoactive layers owing to the presence of distinct crystalline grains has been generally neglected in optical measurements; therefore, the reported results are typically averaged over hundreds or even thousands of such grains. Here we apply femtosecond transient absorption microscopy to spatially and temporally probe ultrafast electronic excited-state dynamics in pristine methylammonium lead tri-iodide (CH3NH3PbI3) thin films and composite structures. We found that the electronic excited-state relaxation kinetics are extremely sensitive to the sample location probed, which was manifested by position-dependent decay time scales and transient signals. Analysis of transient absorption kinetics acquired at distinct spatial positions enabled us to identify contributions of excitons and free charge carriers. PMID- 26267201 TI - Revealing the Mechanism of the Viscous-to-Elastic Crossover in Liquids. AB - In this work, we report on inelastic X-ray scattering experiments combined with the molecular dynamics simulations on deeply supercritical Ar. The presented results unveil the mechanism and regimes of sound propagation in the liquid matter and provide compelling evidence for the adiabatic-to-isothermal longitudinal sound propagation transition. We introduce a Hamiltonian predicting low-frequency transverse sound propagation gaps, which is confirmed by experimental findings and molecular dynamics calculations. As a result, a universal link is established between the positive sound dispersion (PSD) phenomenon and the origin of transverse sound propagation revealing the viscous to-elastic crossover in liquids. The PSD and transverse phononic excitations evolve consistently with theoretical predictions. Both can be considered as a universal fingerprint of the dynamic response of a liquid, which is also observable in a subdomain of supercritical phase. The simultaneous disappearance of both these effects at elevated temperatures is a manifestation of the Frenkel line. We expect that these findings will advance the current understanding of fluids under extreme thermodynamic conditions. PMID- 26267202 TI - Controlling Exciton Diffusion and Fullerene Distribution in Photovoltaic Blends by Side Chain Modification. AB - The influence of crystallinity on exciton diffusion and fullerene distribution was investigated by blending amorphous and semicrystalline copolymers. We measured exciton diffusion and fluorescence quenching in such blends by dispersing fullerene molecules into them. We find that the diffusion length is more than two times higher in the semicrystalline copolymer than in the amorphous copolymer. We also find that fullerene preferentially mixes into disordered regions of the polymer film. This shows that relatively small differences in molecular structure are important for exciton diffusion and fullerene distribution. PMID- 26267203 TI - Deuteration of Perylene Enhances Photochemical Upconversion Efficiency. AB - Photochemical upconversion via triplet-triplet annihilation is a promising technology for improving the efficiency of photovoltaic devices. Previous studies have shown that the efficiency of upconversion depends largely on two rate constants intrinsic to the emitting species. Here, we report that one of these rate constants can be altered by deuteration, leading to enhanced upconversion efficiency. For perylene, deuteration decreases the first order decay rate constant by 16 +/- 9% at 298 K, which increases the linear upconversion response by 45 +/- 21% in the low excitation regime. PMID- 26267204 TI - Journal Impact Factor and the Real Impact of Your Paper. PMID- 26267205 TI - Absorption and Magnetic Circular Dichroism Analyses of Giant Zeeman Splittings in Diffusion-Doped Colloidal Cd(1-x)Mn(x)Se Quantum Dots. AB - Impurity ions can transform the electronic, magnetic, or optical properties of colloidal quantum dots. Magnetic impurities introduce strong dopant-carrier exchange coupling that generates giant Zeeman splittings (DeltaEZ) of excitonic excited states. To date, DeltaEZ in colloidal doped quantum dots has primarily been quantified by analysis of magnetic circular dichroism (MCD) intensities and absorption line widths (sigma). Here, we report DeltaEZ values detected directly by absorption spectroscopy for the first time in such materials, using colloidal Cd(1-x)Mn(x)Se quantum dots prepared by diffusion doping. A convenient method for decomposing MCD and absorption data into circularly polarized absorption spectra is presented. These data confirm the widely applied MCD analysis in the low field, high-temperature regime, but also reveal a breakdown at low temperatures and high fields when DeltaEZ/sigma approaches unity, a situation not previously encountered in doped quantum dots. This breakdown is apparent for the first time here because of the extraordinarily large DeltaEZ and small sigma achieved by nanocrystal diffusion doping. PMID- 26267206 TI - Charge Carriers in Planar and Meso-Structured Organic-Inorganic Perovskites: Mobilities, Lifetimes, and Concentrations of Trap States. AB - Efficient solar cells have been obtained using thin films of solution-processed organic-inorganic perovskites. However, there remains limited knowledge about the relationship between preparation route and optoelectronic properties. We use complementary time-resolved microwave conductivity (TRMC) and photoluminescence (PL) measurements to investigate the charge carrier dynamics in thin planar films of CH3NH3PbI(3-x)Cl(x), CH3NH3PbI3, and their meso-structured analogues. High mobilities close to 30 cm(2)/(V s) and microsecond-long lifetimes are found in thin films of CH3NH3PbI(3-x)Cl(x), compared to lifetimes of only a few hundred nanoseconds in CH3NH3PbI3 and meso-structured perovskites. We describe our TRMC and PL experiments with a global kinetic model, using one set of kinetic parameters characteristic for each sample. We find that the trap density is less than 5 * 10(14) cm(-3) in CH3NH3PbI(3-x)Cl(x), 6 * 10(16) cm(-3) in the CH3NH3PbI3 thin film and ca. 10(15) cm(-3) in both meso-structured perovskites. Furthermore, our results imply that band-to-band recombination is enhanced by the presence of dark carriers resulting from unintentional doping of the perovskites. Finally, our general approach to determine concentrations of trap states and dark carriers is also highly relevant to other semiconductor materials. PMID- 26267207 TI - Understanding the Interaction between Low-Energy Electrons and DNA Nucleotides in Aqueous Solution. AB - Reactions that can damage DNA have been simulated using a combination of molecular dynamics and density functional theory. In particular, the damage caused by the attachment of a low energy electron to the nucleobase. Simulations of anionic single nucleotides of DNA in an aqueous environment that was modeled explicitly have been performed. This has allowed us to examine the role played by the water molecules that surround the DNA in radiation damage mechanisms. Our simulations show that hydrogen bonding and protonation of the nucleotide by the water can have a significant effect on the barriers to strand breaking reactions. Furthermore, these effects are not the same for all four of the bases. PMID- 26267208 TI - Two-Dimensional Indium Selenides Compounds: An Ab Initio Study. AB - We use first-principle calculations to investigate the electronic structure of InSe and In2Se3. The interlayer binding energy is found to be in the same range as for other 2D systems, and the monolayers are found to be dynamically stable, which suggest the possibility to obtain them as isolated layers. The GW approximation including spin-orbit is used to obtain the bandgaps, which are in the range relevant for application in electronics. Also, it is shown that an electric field perpendicular to the layers can induce a semiconductor to metal transition in this family of compounds. PMID- 26267209 TI - Spontaneous Oxidation of Ni Nanoclusters on MgO Monolayers Induced by Segregation of Interfacial Oxygen. AB - We report the study of Ni nanoclusters deposited on MgO/Ag(100) ultrathin films (one monolayer) at T = 200 K. We show by STM analysis and DFT calculations that in the limit of low Ni coverage the formation of nanoclusters of four to six atoms occurs and that these aggregates are flat rather than 3D, as expected for Ni tetramers, pentamers, or hexamers. Both the shape of the clusters and the interatomic distance between neighboring Ni atoms are indicative that the nanoparticles do not consist of pure metal atoms but that a NiyOx structure has formed thanks to the availability of atomic oxygen accumulated at the MgO/Ag interface, with Ni clusters acting as oxygen pumps. Besides being of relevance in view of the use of metal nanoclusters in catalysis and other applications, this finding gives a further proof of the peculiar behavior of ultrathin oxide films. PMID- 26267210 TI - Dynamics of a One-Dimensional Holstein Polaron with the Hierarchical Equations of Motion Approach. AB - Dynamics of a one-dimensional Holstein molecular crystal model is investigated by making use of the hierarchical equations of motion (HEOM) introduced by Tanimura and Kubo [J. Phys. Soc. Jpn. 1989, 104, 101]. Our extended, numerically exact HEOM approach is capable of treating exciton-phonon coupling in a nonperturbative manner and is applicable to any temperature. It is revealed that strong exciton phonon coupling leads to excitonic localization, while a large exciton transfer integral facilitates exciton transport. Temperature effects on excitonic scattering have also been examined. A proof of concept, our work also serves as a benchmark for future comparisons with other numerical approaches to Holstein polaron dynamics. PMID- 26267211 TI - Tyrosine Photophysics During the Early Stages of beta-Amyloid Aggregation Leading to Alzheimer's. AB - We have monitored the formation of toxic beta-amyloid oligomers leading to Alzheimer's disease by detecting changes in the fluorescence decay of intrinsic tyrosine. A new approach based on the non-Debye model of fluorescence kinetics resolves the complexity of the underlying photophysics. The gradual disappearance of nonmonotonic fluorescence decay rates, at the early stages of aggregation as larger, tighter-packed oligomers are formed, is interpreted in terms of tyrosine peptide dielectric relaxation influencing the decay. The results demonstrate the potential for a new type of fluorescence lifetime sensing based on dual excited state/dielectric relaxation, with application across a broad range of biological molecules. The results also reconcile previously conflicting models of protein intrinsic fluorescence decay based on rotamers or dielectric relaxation by illustrating conditions under which both are manifest. PMID- 26267212 TI - Boron Subphthalocyanines as Triplet Harvesting Materials within Organic Photovoltaics. AB - Singlet fission, the generation of two excited triplet states from a single absorbed photon, is currently an area of significant interest to photovoltaic researchers. In this Letter, we outline how a polychlorinated boron subphthalocyanine, previously hypothesized to be an effective harvester of singlet fission derived triplets from pentacene, is relatively efficient at facilitating the process. As expected, we found a major increase in photocurrent generation at the expense of device voltage. For a direct point of comparison, we also have paired the same polychlorinated boron subphthalocyanine with alpha sexithiophene to probe the alternative technique of complementary absorption engineering. The sum of these efforts have let us present new guidelines for the molecular design of boron subphthalocyanine for organic photovoltaic applications. PMID- 26267213 TI - Reduction-induced facile isomerisation of metallacarboranes: synthesis and crystallographic characterisation of 4-Cp-4,1,2-closo-CoC2B9H11. AB - One-electron reduction of 3-Cp-3,1,2-closo-CoC2B9H11 followed by heating to reflux in DME (b.p. 85 degrees C) induces isomerisation to 4-Cp-4,1,2-closo CoC2B9H11, a compound previously only synthesised at much higher temperatures (>380 degrees C). The 4,1,2-isomer has been thoroughly characterised both spectroscopically and crystallographically. PMID- 26267214 TI - Ultralow Friction of Steel Surfaces Using a 1,3-Diketone Lubricant in the Thin Film Lubrication Regime. AB - Ultralow friction (coefficient of friction MU ~ 0.005) is observed when two steel surfaces are brought into sliding contact in the presence of a particular 1,3 diketone lubricant (1-(4-ethyl phenyl) nonane-1,3-dione). We investigate the friction process of such a system both experimentally and theoretically and show that the superlubricity is caused by a novel, unique mechanism: The formation of iron-1,3-diketonato complexes during frictional contact leads to a self-limiting, tribochemical polishing process while at the same time a self-assembled monolayer of the diketone is formed on the employed steel surfaces. This polishing process reduces the contact pressure and at the same time leads to formation of a boundary lubricant layer. During sliding the system transits from the original boundary lubrication regime toward hydrodynamic lubrication. Conductivity measurements across the friction gap during sliding show that the lubricant layer present in the gap between the two shearing surfaces is a only few 10 nanometers thick, so that the molecules experience under typical sliding conditions shear rates of a few 10(6) s(-1). Simulations show that under such strong shear the molecules become strongly oriented in the friction gap and the effective viscosity in sliding direction is significantly reduced so that the system is in the thin film lubrication regime and superlubricity is observed. The results of the experiments suggest that such diketones are promising lubricants to achieve a decrease of energy loss and frictional damage in steel based mechanical devices. PMID- 26267215 TI - Prevalence and detection of neuropsychiatric adverse effects during hepatitis C treatment. AB - BACKGROUND: Current treatment combinations for chronic hepatitis C virus infection still include pegylated interferon and ribavirin despite the new therapeutic options available. Interferon-based treatments are associated with a high incidence of adverse effects. Central nervous system events are among the most frequent adverse drug reactions and their influence on treatment adherence and effectiveness is controversial. OBJECTIVE: The aim of the study was to evaluate neuropsychiatric adverse effects of interferon-based treatment for chronic hepatitis C in standard multidisciplinary clinical practice. Risk factors for these adverse effects and their impact on adherence and sustained viral response were also evaluated. Setting Ambulatory care pharmacy in coordination with the liver unit and the infectious diseases unit at a 650-bed tertiary university hospital. METHODS: We included all consecutive patients with chronic hepatitis C who completed treatment with pegylated interferon and ribavirin between 2005 and 2013. All patients underwent a multidisciplinary follow-up during treatment. MAIN OUTCOME MEASURES: Neuropsychiatric adverse effects were evaluated in relation to severity, management and outcome. The presence of anxiety and depression was evaluated by means of specific tests. RESULTS: A total of 717 treatments in 679 patients were included. During treatment, we detected 1679 neuropsychiatric adverse effects in 618 patients (86.2 %), generating 1737 clinical interventions. Fifty-seven (3.3 %) neuropsychiatric adverse effects were severe and 2 (0.1 %) were life-threatening (suicidal attempts). Most neuropsychiatric adverse effects (1555 events, 92.6 %) resolved without sequelae. Psychiatric medication was required in 289 patients (40.3 %). Sustained viral response was achieved in 400 cases (55.8 %) and was associated with adherence (OR = 1.942, 95 % CI = 1.235-3.052, p = 0.004). A multivariate analysis did not show any relationship between neuropsychiatric adverse effects and treatment adherence or sustained viral response. A psychiatric history was a strong risk factor for depression, anxiety and other psychiatric disorders during treatment. CONCLUSION: Neuropsychiatric adverse effects during interferon-based treatments in patients with chronic hepatitis C were common but mostly mild or moderate. Early detection and accurate multidisciplinary management avoided treatment discontinuation, ensuring adherence and attaining sustained viral response. The identified risk factors could be used to determine patients eligible for interferon-free combinations, thus optimizing health system economics. PMID- 26267217 TI - Enhancer additivity and non-additivity are determined by enhancer strength in the Drosophila embryo. AB - Metazoan genes are embedded in a rich milieu of regulatory information that often includes multiple enhancers possessing overlapping activities. In this study, we employ quantitative live imaging methods to assess the function of pairs of primary and shadow enhancers in the regulation of key patterning genes-knirps, hunchback, and snail-in developing Drosophila embryos. The knirps enhancers exhibit additive, sometimes even super-additive activities, consistent with classical gene fusion studies. In contrast, the hunchback enhancers function sub additively in anterior regions containing saturating levels of the Bicoid activator, but function additively in regions where there are diminishing levels of the Bicoid gradient. Strikingly sub-additive behavior is also observed for snail, whereby removal of the proximal enhancer causes a significant increase in gene expression. Quantitative modeling of enhancer-promoter interactions suggests that weakly active enhancers function additively while strong enhancers behave sub-additively due to competition with the target promoter. PMID- 26267216 TI - Predicting effective microRNA target sites in mammalian mRNAs. AB - MicroRNA targets are often recognized through pairing between the miRNA seed region and complementary sites within target mRNAs, but not all of these canonical sites are equally effective, and both computational and in vivo UV crosslinking approaches suggest that many mRNAs are targeted through non canonical interactions. Here, we show that recently reported non-canonical sites do not mediate repression despite binding the miRNA, which indicates that the vast majority of functional sites are canonical. Accordingly, we developed an improved quantitative model of canonical targeting, using a compendium of experimental datasets that we pre-processed to minimize confounding biases. This model, which considers site type and another 14 features to predict the most effectively targeted mRNAs, performed significantly better than existing models and was as informative as the best high-throughput in vivo crosslinking approaches. It drives the latest version of TargetScan (v7.0; targetscan.org), thereby providing a valuable resource for placing miRNAs into gene-regulatory networks. PMID- 26267218 TI - Biomechanical comparison of bionic, screw and Endobutton fixation in the treatment of tibiofibular syndesmosis injuries. AB - BACKGROUND: The two prevalent fixation methods in the treatment of syndesmosis injuries, the rigid screw fixation and flexible Endobutton fixation, are not without issues; thus, we have designed a novel bionic fixation method which combines the features of both rigid and flexible fixations. The aim of this study was to compare the biomechanical properties of the bionic fixation to the screw and Endobutton fixations. METHODS: Six normal fresh-frozen legs from amputation surgery were used. After initial tests of intact syndesmosis, screw, bionic and Endobutton fixations were performed sequentially for each specimen. Axial loading as well as rotation torque were applied, in five different ankle positions: neutral position, dorsiflexion, plantar flexion, varus, and valgus. The displacement of the syndesmosis and the tibial strain were analysed using a biomechanical testing system. RESULTS: Whether receiving axial loading or rotation torque, in most situations (neutral position, dorsiflexion, varus, plantar flexion with low loading, valgus with high loading, internal and external rotation), the bionic group and Endobutton group had comparable displacements, and there was no significant difference among the intact, bionic, and Endobutton groups; whereas the displacements of the screw group were smaller than any of the other three groups. Results of the tibial strain were similar with that of the displacement. CONCLUSIONS: The bionic fixation at least equals the performance of Endobutton fixation; it also allows more physiologic movement of the syndesmosis when compared to the screw fixation and may serve as a viable option for the fixation of the tibiofibular syndesmosis. PMID- 26267219 TI - Rupatadine is effective in the treatment of chronic spontaneous urticaria in children aged 2-11 years. AB - BACKGROUND: Recommendations in current guidelines for the treatment of chronic spontaneous urticaria (CSU) in infants and children are mostly based on extrapolation of data obtained in adults. This study reports the efficacy and safety of rupatadine, a modern H1 and PAF antagonist recently authorized in Europe for children with allergic rhinitis and CSU. METHODS: A double-blind, randomized, parallel-group, multicentre, placebo-controlled compared study to desloratadine was carried out in children aged 2-11 years with CSU, with or without angio-oedema. Patients received either rupatadine (1 mg/ml), or desloratadine (0.5 mg/ml) or placebo once daily over 6 weeks. A modified 7-day cumulative Urticaria Activity Score (UAS7) was employed as the primary end-point. RESULTS: The absolute change of UAS7 at 42 days showed statistically significant differences between active treatments vs. placebo (-5.5 +/- 7.5 placebo, -11.8 +/ 8.7 rupatadine and -10.6 +/- 9.6 desloratadine; p < 0.001) and without differences between antihistamines compounds. There was a 55.8% decrease for rupatadine followed by desloratadine (-48.4%) and placebo (-30.3%). Rupatadine but not desloratadine was statistically superior to placebo in reduction of pruritus (-57%). Active treatments also showed a statistically better improvement in children's quality of life compared to placebo. Adverse events were uncommon and non-serious in both active groups. CONCLUSION: Rupatadine is effective and well tolerated in the relief of urticaria symptoms, improving quality of life over 6 weeks in children with CSU. This is the first study using a modified UAS to assess severity and efficacy outcome in CSU in children. PMID- 26267220 TI - The roles of nanocarriers on pigment epithelium-derived factor in the differentiation of human cardiac stem cells. AB - Over the past decade, adult stem cells have attracted great attention because of their ability to potentially regenerate desired tissues or entire organs. With the emergence of nanomaterial-based gene therapy, adult stem cells have been considered as a proper tool for the biomedical field. In this study, we utilized organically modified silica (ORMOSIL) nanoparticles to deliver small interfering RNA (siRNA) against pigment epithelium-derived factor (PEDF) and induce the differentiation of human cardiac stem cells (CSCs). We found that the down regulation of PEDF can inhibit the proliferation of human CSCs and induce cell differentiation. To further study the mechanism, we have tested the Notch signalling pathway genes, Hes1 and Hes5, and found that their expressions were inhibited by the PEDF down-regulation. Furthermore, with the restoration of PEDF, both the proliferation of human CSCs and expressions of Hes1 and Hes5 were recovered. Our results suggest for the first time the use of ORMOSIL as nanocarriers for the delivery of PEDF siRNA in human CSCs, and demonstrated the cooperation between PEDF and the Notch signalling pathway in maintaining the self renewal and pluripotency of stem cells. PEDF as the essential controller in differentiation may be a promising target for the regulation of cardiac homeostasis and damage repair, which opens new treatment strategies using nanomaterials for heart disease therapy. PMID- 26267221 TI - Kupffer-cell-expressed transmembrane TNF-alpha is a major contributor to lipopolysaccharide and D-galactosamine-induced liver injury. AB - Tumor necrosis factor (TNF)-alpha exists in two bioactive forms, a 26-kDa transmembrane form (tmTNF-alpha) and a 17-kDa soluble form (sTNF-alpha). sTNF alpha has been recognized as a key regulator of hepatitis; however, serum sTNF alpha disappears in mice during the development of severe liver injury, and high levels of serum sTNF-alpha do not necessarily result in liver damage. Interestingly, in a mouse model of acute hepatitis, we have found that tmTNF alpha expression on Kupffer cells (KCs) significantly increases when mice develop severe liver injury caused by lipopolysaccharide (LPS)/D-galactosamine (D-gal), and the level of tmTNF-alpha expression is positively related to the activity of serum transaminases. Therefore, we hypothesized that KC-expressed tmTNF-alpha constitutes a pathomechanism in hepatitis and have explored the role of tmTNF alpha in this disease model. Here, we have compared the impact of KCs(tmTNFlow) and KCs(tmTNFhigh) on acute hepatitis in vivo and ex vivo and have further demonstrated that KCs(tmTNFhigh), rather than KCs(tmTNFlow), not only exhibit an imbalance in secretion of pro- and anti-inflammatory cytokines, favoring inflammatory response and exacerbating liver injury, but also induce hepatocellular apoptosis via tmTNF-alpha and the expression of another pro apoptotic factor, Fas ligand. Our data suggest that KC(tmTNFhigh) is a major contributor to liver injury in LPS/D-gal-induced hepatitis. PMID- 26267222 TI - Mechanism of Li intercalation/deintercalation into/from the surface of LiCoO2. AB - Mechanism of Li diffusion at the LiCoO2(101[combining overline]4) surface and in bulk LiCoO2 is studied using density functional theory calculations. We find that there is almost no barrier for the diffusion of Li between the two topmost surface layers. The results show that Li intercalation occurs by the diffusion of Li ions from the first layer to the divacancy of Li sites created by removal of two neighboring Li ions in the first and second layer. However, Li deintercalation occurs by the diffusion of Li ions from the second layer to the missing row of topmost Li sites. The energy barrier for the process of intercalation/deintercalation of Li between the second and third surface layers is also lower than that in the bulk. This finding indicates that nanosized LiCoO2 with a large surface area/volume ratio is a promising cathode material for fast charging/discharging Li-ion batteries. PMID- 26267223 TI - Transmission-less attenuation estimation from time-of-flight PET histo-images using consistency equations. AB - In positron emission tomography (PET) imaging, attenuation correction with accurate attenuation estimation is crucial for quantitative patient studies. Recent research showed that the attenuation sinogram can be determined up to a scaling constant utilizing the time-of-flight information. The TOF-PET data can be naturally and efficiently stored in a histo-image without information loss, and the radioactive tracer distribution can be efficiently reconstructed using the DIRECT approaches. In this paper, we explore transmission-less attenuation estimation from TOF-PET histo-images. We first present the TOF-PET histo-image formation and the consistency equations in the histo-image parameterization, then we derive a least-squares solution for estimating the directional derivatives of the attenuation factors from the measured emission histo-images. Finally, we present a fast solver to estimate the attenuation factors from their directional derivatives using the discrete sine transform and fast Fourier transform while considering the boundary conditions. We find that the attenuation histo-images can be uniquely determined from the TOF-PET histo-images by considering boundary conditions. Since the estimate of the attenuation directional derivatives can be inaccurate for LORs tangent to the patient boundary, external sources, e.g. a ring or annulus source, might be needed to give an accurate estimate of the attenuation gradient for such LORs. The attenuation estimation from TOF-PET emission histo-images is demonstrated using simulated 2D TOF-PET data. PMID- 26267224 TI - Dissecting ancestry genomic background in substance dependence genome-wide association studies. AB - AIMS: To understand the role of ancestral genomic background in substance dependence (SD) genome-wide association studies (GWAS), we analyzed population diversity at genetic loci associated with SD traits and evaluated its effect on GWAS outcomes. MATERIALS & METHODS: We investigated 24 genes with variants associated with SD by GWAS; and 82 loci with putative subordinate roles with respect to SD-associated genes. RESULTS: We observed high ancestry-related frequency differences in common functional alleles in GWAS relevant genes and their interactive partners. Common functional alleles with high frequency differences demonstrated significant effects on the GWAS outcomes. CONCLUSION: Population differences in SD GWAS outcomes seem not to be influenced by general variation across the genome, but by ancestry-related local haplotype structures at SD-associated loci. PMID- 26267225 TI - Female Urethral Diverticulum: Current Diagnosis and Management. AB - While urethral diverticulum (UD) affects less than 20 per 1,000,000 women overall, it is thought to represent 1.4% of women with incontinence presenting to urology practices. It is hypothesized to evolve from periurethral glands that become obstructed, infected, and dilated over time, and patients typically present with dyspareunia, bothersome lower urinary tract symptoms (LUTS), and/or recurrent UTIs. In many patients, a periurethral mass can be appreciated on exam. In recent years, magnetic resonance imaging (MRI) has become the imaging test of choice for diagnosis of UD, but ultrasound (US) is a readily available alternative and provides good specificity at a lower cost. Surgical excision of the diverticulum with tension-free, water-tight, three-layer closure continues to be the mainstay of treatment of UD with most studies reporting cure rates of >90%. Concomitant treatment of preexisting stress incontinence with autologous fascial pubovaginal sling can be used at the time of diverticulectomy to avoid a secondary procedure. However, since secondary anti-incontinence procedures are needed in only a small number of patients, up-front stress incontinence treatment may result in significant overtreatment, and staged anti-incontinence procedures continue to be a reasonable option for patients with persistent bothersome stress urinary incontinence (SUI) after diverticulectomy. PMID- 26267226 TI - What is the Need for Prostatic Biomarkers in Prostate Cancer Management? AB - Discriminating patients with a low risk of progression from those with lethal prostate cancer is one of the main challenges in prostate cancer management. Indeed, such discrimination is essential if we aim to avoid overtreatment in men with indolent disease and to improve survival in those men with lethal disease. We are reporting on the current literature on such prognostic tools that are now available, their clinical role and their limitations in individualizing care. There is an urgent need to incorporate such genomic tools into new platform-based clinical trial structures to further develop and validate prognostic and predictive biomarkers and provide prostate cancer patients with an effective and cost-efficient access to new drugs in the setting of personalized treatment. PMID- 26267227 TI - Room temperature Coulomb blockade effects in Au nanocluster/pentacene single electron transistors. AB - Single-electron transistors incorporating single ~1 nm gold nanocluster (AuNCs) and pentacene as a complex charge transport system have been used to study the quantum Coulomb blockade and its single electron tunnelling behaviour at room temperature (RT) (300 K). Monodisperse ultra-small (0.86 +/- 0.30 nm) AuNCs were deposited by the tilted-target sputtering technique into 12 nm nanogaps fabricated by high-resolution e-beam lithography. Tunnelling resistance was modulated to ~10(9) Omega by addition of a pentacene layer, allowing clear observation of quantum staircases and Coulomb oscillations with on/off current modulation ratio of ~100 in RT current-voltage measurements. The electron addition energy and average quantized energy level spacing were found to be 282 and 80.4 meV, respectively, which are significantly larger than the thermal energy at 300 K (25.9 meV). PMID- 26267228 TI - Development of the Superaltricial Monk Parakeet (Aves, Psittaciformes): Embryo Staging, Growth, and Heterochronies. AB - Knowledge about the embryonic stages of birds is important in answering many questions about development and evolution. We give the first description of 41 embryological stages of the monk parakeet (Myiopsitta monachus) on the basis of external morphology and comparison with the chicken. We also provide measurements of some external morphological characters (i.e. body mass, crown-rump, beak, forelimb, and third toe lengths) and perform comparisons with other precocial and altricial birds with the aim of identifying heterochronous developmental features. The following differences in the development of characters in the monk parakeet when compared with other birds were found: (1) delay of the feathers primordia, (2) wing buds initially greater than leg buds, (3) forelimbs and hindlimbs with similar relative size, (4) retroversion of the toe IV, (5) ventral curvature of the upper jaw, (6) positive regressions between stages and beak length with acceleration and higher values and III toe lengths with deceleration and lower values in the monk parakeet compared to the chicken. The growth pattern of the monk paraket Myiopsitta monachus could be influenced by some heterochronic processes like post-displacement, acceleration and/or deceleration. Results of this research allow the standard identification of stages in different species of parrots, recognize similarities and differences between precocial (the chicken) and altricial species (Myiopsitta), and provide planning data for future studies. PMID- 26267230 TI - Corrigendum to: Genetic associations of leukoaraiosis indicate pathophysiological mechanisms in white matter lesions etiology. PMID- 26267229 TI - Integrated in silico and experimental methods revealed that Arctigenin inhibited angiogenesis and HCT116 cell migration and invasion through regulating the H1F4A and Wnt/beta-catenin pathway. AB - Arctigenin (ARG) has been previously reported to exert diverse biological activities including anti-proliferation, anti-inflammatory, and antiviral, etc. In the current study, the anti-metastasis and anti-angiogenesis activities of ARG were investigated. To further understand how ARG played these bioactivities, proteomic approaches were used to profile the proteome changes in response to ARG treatment using 2DE-MS/MS. Using these approaches, a total of 50 differentially expressed proteins were identified and clustered. Bioinformatics analysis suggested that multiple signalling pathways were involved. Moreover, ARG induced anti-metastatic and anti-angiogenesis activities were mainly accompanied by a deactivation of the Wnt/beta-catenin pathway in HCT116 cells. PMID- 26267231 TI - Compact and stable SNAP ligand-conjugated quantum dots as a fluorescent probe for single-molecule imaging of dynein motor protein. AB - Compact SNAP ligand-conjugated quantum dots (<10 nm) with high colloidal stability over a wide range of pH (5-9) have been synthesized as fluorescent probe for the single-molecule imaging of dynein motor protein. PMID- 26267233 TI - Adult-onset congenital thrombotic thrombocytopenic purpura caused by a novel compound heterozygous mutation of the ADAMTS13 gene. AB - Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease, characterized by microangiopathic hemolytic anaemia and thrombocytopenia, resulting in neurologic and/or renal abnormalities. We report a 49-year-old patient with a history of thrombotic events, renal failure, and thrombocytopenia. Blood analysis demonstrated no ADAMTS13 activity in the absence of antibodies against ADAMTS13. The complete ADAMTS13 gene was sequenced, and two mutations were identified: one mutation on exon 24 (Arg1060Asp), which had previously been described, and a mutation on exon 27 (Met1260IlefsX34), which has not been reported. For these mutations, compound heterozygosity appears to be necessary to cause TTP, as family members of the patient display only one of the mutations and all displayed normal ADAMTS13 activity. PMID- 26267232 TI - The longitudinal analysis of large granular lymphocytosis in patients with Philadelphia chromosome-positive leukemia treated with dasatinib. AB - Dasatinib, a 2nd-generation tyrosine kinase inhibitor (TKI), can specifically induce large granular lymphocytes (LGL) in some patients with Philadelphia chromosome (Ph)-positive leukemia. To investigate the properties of the induced LGLs, we performed prospective and longitudinal analyses. From Feb 2011 to Jan 2013, a total of 17 patients with Ph-positive leukemia who were previously untreated or refractory to imatinib were enrolled. T cell receptor (TCR) gamma/delta gene rearrangements and phenotypic profiles of lymphocytes were examined before and during administration of dasatinib. LGL lymphocytosis was observed in half of the dasatinib-treated cases (LGL+ group), showing a relation to increased achievement of complete cytogenetic response within 6 months. The phenotypes of the increased lymphocytes were revealed to be mostly natural killer cells. In the LGL+ group, clonal TCR-gamma gene rearrangements were frequently detected at diagnosis (six of nine cases) and persisted during therapy, compared with only two of eight in the LGL- group. The proportion of regulatory T cells to CD4+ T cells at diagnosis was lower in the LGL+ compared with the LGL- group (median 4.2 vs. 6.6 %), and this disparity was sustained throughout the therapeutic period. These results demonstrate that immunological condition at diagnosis may affect LGL lymphocytosis in some dasatinib-treated patients. PMID- 26267234 TI - Erratum to: Bone geometry, bone mineral density, and micro-architecture in patients with myelofibrosis: a cross-sectional study using DXA, HR-pQCT, and bone turnover markers. PMID- 26267235 TI - SNAPPE II Score As a Predictor of Survival in Neonates with Congenital Diaphragmatic Hernia: A Single Center Experience. AB - Introduction Prediction of mortality and morbidity in newborns with congenital diaphragmatic hernia (CDH) is too complex for practical use and may not be accurate. The main objective of this study was to evaluate the usefulness of the CDH Study Group equation and Score of Neonatal Acute Physiology Perinatal Extension (SNAPPE) II score to predict short-term outcomes of newborns with CDH. Materials and Methods Fifty-two neonates were admitted with CDH at Children's Hospital of Michigan from November 2001 to July 2009. Retrospective chart analysis was performed. Predicted survival rates were calculated using the equation published by the CDH Study Group in 2001. SNAPPE II scores were also obtained within 12 hours of admission. Statistical analysis was performed using SPSS statistical package. Results Thirty out of 52 (58%) neonates survived to discharge. SNAPPE II score was significantly lower (p < 0.0001) in survivors (20 +/- 15) versus nonsurvivors (41 +/- 16). When neonates were stratified according to the CDH Study Group, low-risk patients had a survival rate of 68% (predicted 84%), moderate-risk patients had a survival rate of 43% (predicted 57%), and high risk patients had a survival rate of 33% (predicted 36%). A total of 83% of the newborns who survived were operated within 48 hours of life, while only 17% of the nonsurvivors were operated within 48 hours of life. Conclusion SNAPPE II scores were better predictors of mortality than the CDH Study Group equation published in 2001. Further exploration is warranted to evaluate validity of survival advantage for those who were operated within 48 hours of life. A future study of combination of prenatal and postnatal factors may help in improved outcomes of the newborns with CDH. PMID- 26267236 TI - Body location and tail regeneration effects on osteoderms morphology-are they useful tools for systematic, paleontology, and skeletochronology in diploglossine lizards (squamata, anguidae)? AB - Although diploglossine osteoderms were mentioned in several systematic and paleontological studies, their morphological variability in single specimens or within species remains paradoxically undescribed. This is mainly the effect of the lack of attention paid hitherto to the morphological and histological characteristics of the tail osteoderms. This study demonstrated that a previously undescribed morphological variability exists in these osteoderms, especially in those resulting from tail regeneration. Indeed, regenerated osteoderms display a plesiomorphic anguid morphology that was previously considered to be absent in Diploglossinae. We also provide the first histological description of diploglossine osteoderms and new information about the obvious differences in growth dynamic between regenerated and nonregenerated osteoderms. These new data raise questions about the usefulness of diploglossine osteoderms in systematic, paleontological, and skeletochronological studies. Our study shows that the exact position on the trunk or on a regenerated or nonregenerated tail of each studied osteoderm must be known in order to avoid mistakes related to their important interspecies and intraspecies variability. PMID- 26267237 TI - Childhood Predictors and Adult Life Success of Adolescent Delinquency Abstainers. AB - While much is known about adolescent delinquency, considerably less attention has been given to adolescent delinquency abstention. Understanding how or why some adolescents manage to abstain from delinquency during adolescence is informative for understanding and preventing adolescent (minor) delinquency. Using data from the Cambridge Study in Delinquent Development (N = 411 males) to compare abstainers, self-report delinquents and convicted delinquents we found five childhood factors (ages 8-10) that predicted adolescent abstention (ages 10-18). First, we find that adolescent abstainers possess characteristics opposite to those of convicted delinquents (namely, abstainers are high on honesty, conformity and family income). However, we also found that abstainers also share some childhood characteristics with convicted delinquents (namely, low popularity and low school achievement). A latent class analysis indicated that the mixed factors predicting abstention can be accounted for by two groups of abstainers: an adaptive group characterized by high honesty, and a maladaptive group characterized by low popularity and low school achievement. Further, validation of these two types of abstainers using data collected at age 48 suggested that adaptive abstainers outperform all other adolescents in general life success, whereas maladaptive abstainers only fare better than delinquent adolescents in terms of lower substance use and delinquency later in life. PMID- 26267238 TI - The Role of Parent Psychopathology in Emotion Socialization. AB - This study examined the relation between parent psychopathology symptoms and emotion socialization practices in a sample of mothers and fathers of preschool aged children with behavior problems (N = 109, M age = 44.60 months, 50 % male). Each parent completed a self-report rating scale of their psychopathology symptoms and audio-recorded naturalistic interactions with their children, which were coded for reactions to child negative affect. Results supported a spillover hypothesis for mothers. Specifically, mothers who reported greater overall psychopathology symptoms, anxiety symptoms, substance use, and borderline and Cluster A personality symptoms were more likely to exhibit non-supportive reactions. Additionally, mothers who reported greater anxiety and Cluster A personality symptoms were more likely to not respond to child negative affect. Compensatory and crossover hypotheses were also supported. Partners of mothers who reported high levels of anxiety were more likely to use supportive reactions to child negative affect. In contrast, partners of mothers who reported high levels of borderline and Cluster A personality symptoms and overall psychopathology symptoms were more likely to show non-supportive reactions. With the exception of borderline personality symptoms, fathers' psychopathology was unrelated to parental responses to child negative affect. Results highlight the importance of maternal psychopathology in parental emotion socialization practices. PMID- 26267239 TI - A comparative public health and budget impact analysis of pneumococcal vaccines: The French case. AB - In 2002, a pneumococcal conjugate vaccine (PCV) was introduced to French infants and toddlers. A change has been witnessed in the incidence of pneumococcal diseases in adults: the incidence of invasive pneumococcal disease (IPD) of serotypes covered by PCV decreased, and serotypes not covered by PCV increased. This study aimed to quantify the public health and budget impact of pneumococcal vaccination strategies in at-risk adults in France over 5 years. A previously published population-based Markov model was adapted to the French situation. At risk adults received either PPV23 (pneumococcal polysaccharide vaccine; for the immunocompetent) or PCV13 (for the immunosuppressed). The strategy was compared to PCV13 alone. Uncertainty was addressed using extreme scenario analyses. Between 2014 and 2018, vaccination with PPV23/PCV13 led to a higher reduction in terms of IPD and non-bacteremic pneumococcal pneumonia cases avoided in most scenarios analyzed when compared to PCV13 alone. For budget impact, none of the scenarios was in favor of PCV13. Under conservative coverage assumptions, the total incremental budget impact ranged from ? 39.8 million to ? 69.3 million if PCV13 were to replace PPV23 in the immunocompetent. With the epidemiological changes of pneumococcal diseases and the broader serotype coverage of PPV23, the current program remains an optimal strategy from public health perspective. Given the additional budget required for the use of PCV13 alone and its uncertain public health benefits, vaccination with PPV23 remains the preferred strategy. PMID- 26267240 TI - Ethnic variation in colorectal cancer risk following a positive faecal occult blood test in an English bowel cancer screening programme centre. AB - BACKGROUND AND AIMS: The literature on colorectal cancer (CRC) screening and ethnic diversity is dominated by studies from the USA. There are no such published data from the UK bowel cancer screening programme (BCSP) population. The Wolverhampton Bowel Cancer Screening Centre serves a population of 900,000 in the Black Country and South Staffordshire. South Asians (SA) comprise 9% of the population. We aimed to determine the effects of ethnicity and sex on the risk for cancer or adenoma detected by colonoscopy following a positive faecal occult blood test over a 5-year period (2007-2011). METHODS: Data were collected from the prospectively maintained BCSP cohort. South Asian patients were identified and compared with those of non-South Asian ethnicity, and colonoscopy outcomes were determined. RESULTS: A total of 3552 participants underwent BCSP colonoscopy (non-South Asian=3363; SA=189). There were 271 cancers (7.6%) detected within the non-South Asian group and seven cancers (0.2%) in the South Asian population (P<0.05). The probability of colon cancer is higher [odds ratio (OR)=3.84, P<0.05] in non-South Asians compared with South Asians. Patients in the 65-70 year age group have the highest risk (OR=1.60; P<0.05) for CRC. During the study 1313 adenomas were detected. A total of 771 high-risk and intermediate-risk adenomas were detected in the non-South Asian group, and 14 were detected in the South Asian group. The risk of adenoma in non-South Asians is six times higher than in South Asians (OR=5.99, P<0.001) following positive faecal occult blood testing. CONCLUSION: There are fewer colorectal cancers in South Asians compared with the non-South Asian population in this regional study. This is the first such study in the BCSP population. PMID- 26267241 TI - Lemur Biorhythms and Life History Evolution. AB - Skeletal histology supports the hypothesis that primate life histories are regulated by a neuroendocrine rhythm, the Havers-Halberg Oscillation (HHO). Interestingly, subfossil lemurs are outliers in HHO scaling relationships that have been discovered for haplorhine primates and other mammals. We present new data to determine whether these species represent the general lemur or strepsirrhine condition and to inform models about neuroendocrine-mediated life history evolution. We gathered the largest sample to date of HHO data from histological sections of primate teeth (including the subfossil lemurs) to assess the relationship of these chronobiological measures with life history-related variables including body mass, brain size, age at first female reproduction, and activity level. For anthropoids, these variables show strong correlations with HHO conforming to predictions, though body mass and endocranial volume are strongly correlated with HHO periodicity in this group. However, lemurs (possibly excepting Daubentonia) do not follow this pattern and show markedly less variability in HHO periodicity and lower correlation coefficients and slopes. Moreover, body mass is uncorrelated, and brain size and activity levels are more strongly correlated with HHO periodicity in these animals. We argue that lemurs evolved this pattern due to selection for risk-averse life histories driven by the unpredictability of the environment in Madagascar. These results reinforce the idea that HHO influences life history evolution differently in response to specific ecological selection regimes. PMID- 26267242 TI - Novel Penicillin Analogues as Potential Antimicrobial Agents; Design, Synthesis and Docking Studies. AB - A number of penicillin derivatives (4a-h) were synthesized by the condensation of 6-amino penicillinic acid (6-APA) with non-steroidal anti-inflammatory drugs as antimicrobial agents. In silico docking study of these analogues was performed against Penicillin Binding Protein (PDBID 1CEF) using AutoDock Tools 1.5.6 in order to investigate the antimicrobial data on structural basis. Penicillin binding proteins function as either transpeptidases or carboxypeptidases and in few cases demonstrate transglycosylase activity in bacteria. The excellent antibacterial potential was depicted by compounds 4c and 4e against Escherichia coli, Staphylococcus epidermidus and Staphylococcus aureus compared to the standard amoxicillin. The most potent penicillin derivative 4e exhibited same activity as standard amoxicillin against S. aureus. In the enzyme inhibitory assay the compound 4e inhibited E. coli MurC with an IC50 value of 12.5 MUM. The docking scores of these compounds 4c and 4e also verified their greater antibacterial potential. The results verified the importance of side chain functionalities along with the presence of central penam nucleus. The binding affinities calculated from docking results expressed in the form of binding energies ranges from -7.8 to -9.2kcal/mol. The carboxylic group of penam nucleus in all these compounds is responsible for strong binding with receptor protein with the bond length ranges from 3.4 to 4.4 A. The results of present work ratify that derivatives 4c and 4e may serve as a structural template for the design and development of potent antimicrobial agents. PMID- 26267243 TI - Effect of repeated tracheostomy tube reprocessing on biofilm formation. AB - OBJECTIVES/HYPOTHESIS: To determine the effect of repeated reprocessing of pediatric tracheostomy tubes (TTs) on biofilm formation. STUDY DESIGN: In vitro microbiological study. METHODS: Pediatric, uncuffed, polyvinyl chloride (PVC) TTs from two different manufacturers (Tracoe Mini and Shiley) were reprocessed mechanically with household detergent and soaked in sodium hypochlorite (bleach). Two TTs of each brand were reprocessed 0 (control), 10, or 20 times. Twenty 2-mm coupons were then obtained from each TT, immersed in human mucus, and cultured with either Staphylococcus aureus or Pseudomonas aeruginosa. Biofilm formation was evaluated with bacterial counts. RESULTS: Bacterial counts of S. aureus for both brands were significantly higher on the TTs that were reprocessed 20 times compared to those that were not reprocessed (Tracoe: P = .040, Shiley: P < .0001) or those that were reprocessed 10 times (Tracoe: P = .022, Shiley: P = .0002). There was no difference between controls and TTs reprocessed 10 times (Tracoe: P = .76, Shiley: P = .24). P. aeuruginosa counts were not significantly different among the varying numbers of reprocessing cycles for either Tracoe or Shiley TTs (P = .08 and P = .97, respectively). CONCLUSIONS: Repeated reprocessing of PVC TTs with detergent and bleach paradoxically promotes S. aureus biofilm development, possibly due to degradation of the tube surface that facilitates bacterial attachment. Further investigation is needed to determine the optimal technique and limits of reprocessing TTs in clinical practice. LEVEL OF EVIDENCE: NA. PMID- 26267245 TI - Utility of Three-dimensional Echocardiography for Implantation of a Left Ventricular Assist Device. PMID- 26267244 TI - Concurrence of Intraoperative Hypotension, Low Minimum Alveolar Concentration, and Low Bispectral Index Is Associated with Postoperative Death. AB - BACKGROUND: An intraoperative concurrence of mean arterial pressure less than 75 mmHg, minimum alveolar concentration less than 0.8, and bispectral index less than 45 has been termed a "triple low" state. An association between triple low and postoperative mortality has been reported but was not replicated in a subsequent study. The authors pooled existing data from clinical trials to further evaluate the purported association in an observational study. METHODS: This retrospective observational study included 13,198 patients from three clinical trials: B-Unaware, BAG-RECALL, and Michigan Awareness Control Study. Patients with greater than 15 not necessarily consecutive minutes of triple low were propensity matched to controls with similar characteristics and comorbidities. A multivariable Cox proportional hazards model was used to evaluate the association between triple low duration and postoperative mortality. RESULTS: Thirty-day mortality was 0.8% overall, 1.9% in the triple low cohort, and 0.4% in the nontriple low cohort (odds ratio, 5.16; 95% CI, 4.21 to 6.34). After matching and adjusting for comorbidities, cumulative duration of triple low was significantly associated with an increased risk of mortality at 30 days (hazard ratio, 1.09; 95% CI, 1.07 to 1.11, per 15 min) and 90 days (hazard ratio, 1.09; 95% CI, 1.08 to 1.11, per 15 min). CONCLUSION: There is a weak independent association between the triple low state and postoperative mortality, and the propensity-matched analysis does not suggest that this is an epiphenomenon. PMID- 26267247 TI - Study of Nonlinear MHD Tribological Squeeze Film at Generalized Magnetic Reynolds Numbers Using DTM. AB - In the current article, a combination of the differential transform method (DTM) and Pade approximation method are implemented to solve a system of nonlinear differential equations modelling the flow of a Newtonian magnetic lubricant squeeze film with magnetic induction effects incorporated. Solutions for the transformed radial and tangential momentum as well as solutions for the radial and tangential induced magnetic field conservation equations are determined. The DTM-Pade combined method is observed to demonstrate excellent convergence, stability and versatility in simulating the magnetic squeeze film problem. The effects of involved parameters, i.e. squeeze Reynolds number (N1), dimensionless axial magnetic force strength parameter (N2), dimensionless tangential magnetic force strength parameter (N3), and magnetic Reynolds number (Rem) are illustrated graphically and discussed in detail. Applications of the study include automotive magneto-rheological shock absorbers, novel aircraft landing gear systems and biological prosthetics. PMID- 26267248 TI - Selectivity of Organic Products to Trichogramma pretiosum Riley (Hymenoptera: Trichogrammatidae). AB - The selectivity of various entomopathogens and one insecticide (chlorpyrifos = positive control) to Trichogramma pretiosum Riley (Hymenoptera: Trichogrammatidae) was evaluated in the laboratory, using the protocol established by the Working Group on "Pesticides and Beneficial Organisms" of the IOBC. The evaluated parameters were parasitism (%), adult emergence (%), and product repellency to the parasitoid when sprayed on host eggs prior to parasitism (free-choice and no-choice tests). Most of the studied entomopathogens (Bacillus thuringiensis var. kurstaki, Bacillus thuringiensis var. aizawai, Beauveria bassiana, Metarhizium anisopliae, and Trichoderma harzianum) had no effects on biological parameters and were classified as harmless to T. pretiosum. Emergence of parasitoids (progeny viability) was reduced, but remained above 90%, when host eggs were sprayed with Baculovirus anticarsia prior to parasitism in the free-choice test, and B. anticarsia was therefore considered harmless. Chlorpyrifos (positive control) caused high adult parasitoid mortality in all bioassays. While T. pretiosum and the tested entomopathogens may be used simultaneously in integrated pest management programs, the use of chlorpyrifos should be avoided. PMID- 26267246 TI - Characterization of Novel Factors Involved in Swimming and Swarming Motility in Salmonella enterica Serovar Typhimurium. AB - Salmonella enterica utilizes flagellar motility to swim through liquid environments and on surfaces. The biosynthesis of the flagellum is regulated on various levels, including transcriptional and posttranscriptional mechanisms. Here, we investigated the motility phenotype of 24 selected single gene deletions that were previously described to display swimming and swarming motility effects. Mutations in flgE, fliH, ydiV, rfaG, yjcC, STM1267 and STM3363 showed an altered motility phenotype. Deletions of flgE and fliH displayed a non-motile phenotype in both swimming and swarming motility assays as expected. The deletions of STM1267, STM3363, ydiV, rfaG and yjcC were further analyzed in detail for flagellar and fimbrial gene expression and filament formation. A DeltaydiV mutant showed increased swimming motility, but a decrease in swarming motility, which coincided with derepression of curli fimbriae. A deletion of yjcC, encoding for an EAL domain-containing protein, increased swimming motility independent on flagellar gene expression. A DeltaSTM1267 mutant displayed a hypermotile phenotype on swarm agar plates and was found to have increased numbers of flagella. In contrast, a knockout of STM3363 did also display an increase in swarming motility, but did not alter flagella numbers. Finally, a deletion of the LPS biosynthesis-related protein RfaG reduced swimming and swarming motility, associated with a decrease in transcription from flagellar class II and class III promoters and a lack of flagellar filaments. PMID- 26267249 TI - Free and bound excitonic effects in Al0.5Ga0.5N/Al0.35Ga0.65N MQWs with different Si-doping levels in the well layers. AB - Free exciton (FX) and bound exciton (BX) in Al0.5Ga0.5N/Al0.35Ga0.65N multiple quantum wells (MQWs) with different Si-doping levels in the well layers are investigated by photoluminescence (PL) spectra. Low temperature (10 K) PL spectra identify a large binding energy of 87.4 meV for the BX in undoped sample, and 63.6 meV for the BX in Si-doped (2 * 10(18 ) cm(-3)) sample. They are attributed to O-bound and Si-bound excitons, respectively. The large binding energies of BX are assumed to originate from the strong quantum confinement in the quantum wells, which also leads to a stronger FX PL peak intensity in comparison with BX at 10 K. Si-doping is found to suppress the FX quenching by reducing threading dislocation density (TDD) in the well layers, leading to a significant improvement of IQE from 33.7% to 45%. PMID- 26267250 TI - Critical Population Spotlight: HIV and the Garifuna of Honduras--Comment on Gandhi et al. "Migration, Multiple Sexual Partnerships, and Sexual Concurrency in the Garifuna Population of Honduras". PMID- 26267252 TI - Factors Associated to a Reactive Result of Rapid-HIV Test in Socio-culturally Adapted Services in Primary Care in Spain. AB - The Services of Prevention and Early diagnosis of HIV in Madrid (Spain) are set in selected primary care centers. Cultural mediators targeted to vulnerable groups (economic immigrants, MSM, sex workers...) perform risk assessment and counselling. Between 2010 and 2014 they performed 6 039 rapid-HIV test, 27.8 % in MSM, 41.2 % in men who have sex exclusively with women (MSW) and 31.0 % in women; 35.7 % in immigrants, mainly from Latin America. A reactive result was more common among MSM (6.0 %) compared to women (0.6 %) and MSW (0.5 %). In MSM it was associated to being immigrant and to antecedents of sexually transmitted infections (STI). Among MSW the factors associated to a reactive result were: seropositivity of sexual partner and heroine consumption, and in women: infrequent use of condoms, seropositivity of sexual partner and antecedents of STI. Preventive interventions to reduce risk of HIV transmission and for early detection should be adapted and targeted to high risk population. PMID- 26267253 TI - Mediation analysis of an effective sexual health promotion intervention for Spanish adolescents. AB - The objective of this study is to determinate the factors that mediate in the self-reported consistent condom use over the 24-months post-intervention period in adolescents who received COMPAS, a sexual health promotion intervention targeted to Spanish adolescents. Twelve high schools located in Spain were randomized to an intervention or a control group with baseline, immediate-post, 12 and 24-month post-intervention assessments. Self-reported consistent condom use by 24 months post-intervention was the primary outcome. Based on the theory of planned behavior, we identified which theory-based variables mediated the intervention's effect on consistent condom use. Serial multiple mediation analysis indicated that attitudes toward condom use, when there are obstacles to use it, and self-efficacy mediated the COMPAS's effect in increasing consistent condom use. This is the first study that identifies the theoretical constructs that mediate the efficacy of a school-based intervention to promote sexual health in adolescents from Spain. PMID- 26267251 TI - Running Backwards: Consequences of Current HIV Incidence Rates for the Next Generation of Black MSM in the United States. AB - Black men who have sex with men (MSM) in the United States are disproportionately impacted by HIV. To better understand this public health problem, we reviewed the literature to calculate an estimate of HIV incidence among Black MSM. We used this rate to model HIV prevalence over time within a simulated cohort, which we subsequently compared to prevalence from community-based samples. We searched all databases accessible through PubMed, and Conference on Retroviruses and Opportunistic Infections abstracts for HIV incidence estimates among Black MSM. Summary HIV incidence rates and 95 % confidence intervals (CIs) were calculated using random effects models. Using the average incidence rate, we modeled HIV prevalence within a simulated cohort of Black MSM (who were all HIV-negative at the start) from ages 18 through 40. Based on five incidence rates totaling 2898 Black MSM, the weighted mean incidence was 4.16 % per year (95 % CI 2.76-5.56). Using this annual incidence rate, our model predicted that 39.94 % of Black MSM within the simulated cohort would be HIV-positive by age 30, and 60.73 % by 40. Projections were similar to HIV prevalence found in community-based samples of Black MSM. High HIV prevalence will persist across the life-course among Black MSM, unless effective prevention and treatment efforts are increased to substantially reduce HIV transmission among this underserved and marginalized population. PMID- 26267254 TI - Estimation of the number of female sex workers in Yangon and Mandalay, Myanmar. AB - While it is known that HIV prevalence is higher among key affected populations, such as female sex workers (FSW), the sizes of these populations are difficult to estimate. This study aimed to estimate the numbers of FSW in the two largest cities of Myanmar using multiple data-driven methods. A total of 778 FSW (450 in Yangon, 328 in Mandalay) were recruited though time-location sampling during November and December 2013. Five multiplier methods and a modified wisdom of the crowds method were applied within the surveys to calculate the number of FSW in each city. The median of the methods estimated a population size of FSW in Yangon at 4992 (acceptable upper and lower bounds: 4482-5753) and 3315 (2992-3368) in Mandalay. These estimates translate to a population prevalence of FSW among adult women (age 18-49 years) of 0.35 % (0.32-0.40 %) in Yangon and 0.77 % (0.69-0.84 %) in Mandalay. PMID- 26267256 TI - Performance characteristics of Parkour practitioners: Who are the traceurs? AB - Parkour is a modern physical activity that consists of using the environment, mostly urban, as a playground of obstacles. The aims of this study were (i) to investigate age, anthropometric and training characteristics of Parkour practitioners, called 'traceurs' and (ii) to assess jump performances and muscular characteristics of traceurs, compared to those of gymnasts and power athletes. The mean age of the population of traceurs studied (n = 130) was 19.4 +/- 4.3 years, women represented 12.4% of the total field and mean training volume was 8.1 +/- 0.5 hours/week. Vertical and long jump performances were analysed on smaller samples of participants (four groups, n = 15 per group); and eccentric (-90 degrees s(-1), -30 degrees s(-1)), concentric (30 degrees s( 1), 90 degrees s(-1)) and isometric knee extensors torques were evaluated by means of an isokinetic dynamometer. Traceurs showed greater (P < .01) drop jump performance (64.9 +/- 1.5 cm) than gymnasts (60.9 +/- 1.1 cm) and greater (P < .001) counter movement jump with arms (59.2 +/- 1.5 cm) than power athletes (53.0 +/- 1.4 cm). Standing long jump performances were greater (P < .05) for traceurs (282.7 +/- 5.2 cm) compared to other athletes (gymnasts: 273.9 +/- 7.3 cm; power athletes: 261.3 +/- 6.7 cm). Eccentric knee extension torques were greater (P < .05) for traceurs compared to other athletes. This study revealed that Parkour training induces major development of jump and muscular skills. The use of such training has several practical applications as it provides a better resistance to high eccentric load and helps reinforce musculoskeletal structures. PMID- 26267257 TI - Disseminated coccidioidomycosis masquerading as a ruptured epidermal inclusion cyst in a healthy young adult from Philadelphia. PMID- 26267255 TI - Weak protein interactions and pH- and temperature-dependent aggregation of human Fc1. AB - The Fc (fragment crystallizable) is a common structural region in immunoglobulin gamma (IgG) proteins, IgG-based multi-specific platforms, and Fc-fusion platform technologies. Changes in conformational stability, protein-protein interactions, and aggregation of NS0-produced human Fc1 were quantified experimentally as a function of pH (4 to 6) and temperature (30 to 77 degrees C), using a combination of differential scanning calorimetry, laser light scattering, size exclusion chromatography, and capillary electrophoresis. The Fc1 was O glycosylated at position 3 (threonine), and confirmed to correspond to the intact IgG1 by comparison with Fc1 produced by cleavage of the parent IgG1. Changing the pH caused large effects for thermal unfolding transitions, but it caused surprisingly smaller effects for electrostatic protein-protein interactions. The aggregation behavior was qualitatively similar across different solution conditions, with soluble dimers and larger oligomers formed in most cases. Aggregation rates spanned approximately 5 orders of magnitude and could be divided into 2 regimes: (i) Arrhenius, unfolding-limited aggregation at temperatures near or above the midpoint-unfolding temperature of the CH2 domain; (ii) a non-Arrhenius regime at lower temperatures, presumably as a result of the temperature dependence of the unfolding enthalpy for the CH2 domain. The non Arrhenius regime was most pronounced for lower temperatures. Together with the weak protein-protein repulsions, these highlight challenges that are expected for maintaining long-term stability of biotechnology products that are based on human Fc constructs. PMID- 26267258 TI - The removal of chromium (VI) and lead (II) from groundwater using sepiolite supported nanoscale zero-valent iron (S-NZVI). AB - In this study, the synthesis and characterization of sepiolite-supported nanoscale zero-valent iron particles (S-NZVI) was investigated for the adsorption/reduction of Cr(VI) and Pb(II) ions. Nanoscale zero-valent iron (NZVI) supported on sepiolite was successfully used to remove Cr(VI) and Pb(II) from groundwater with high efficiency. The removal mechanism was proposed as a two step interaction including both the physical adsorption of Cr(VI) and Pb(II) on the surface or inner layers of the sepiolite-supported NZVI particles and the subsequent reduction of Cr(VI) to Cr(III) and Pb(II) to Pb(0) by NZVI. The immobilization of the NZVI particles on the surface of sepiolite could help to overcome the disadvantage of NZVI particles, which have strong tendency to agglomerate into larger particles, resulting in an adverse effect on both the effective surface area and reaction performance. The techniques of XRD, XPS, BET, Zeta potential, and TEM were used to characterize the S-NZVI and interaction between S-NZVI and heavy metals. The appropriate S-NZVI dosage was 1.6 g L(-1). The removal efficiency of Cr(VI) and Pb(II) by S-NZVI was not affected to any considerable extent by the presence of co-existing ions, such as H2PO4(-), SiO3(2 ), Ca(2+) and HCO3(-). The Cr(VI) and Pb(II) removal kinetics followed a pseudo first-order rate expression, and both Langmuir isotherm model and Freundlich isotherm model were proposed. The results suggested that supporting NZVI on sepiolite had the potential to become a promising technique for in situ heavy metal-contaminated groundwater remediation. PMID- 26267259 TI - The skin of Commerson's dolphins (Cephalorhynchus commersonii) as a biomonitor of mercury and selenium in Subantarctic waters. AB - The skin of bycaught Commerson's dolphins was tested for mercury (Hg) and selenium (Se) biomonitoring in Subantarctic environments. The correlation of levels detected in the skin with those found in internal tissues - lung, liver, kidney and muscle - was assessed to evaluate how skin represents internal Hg and Se distribution for monitoring purposes. Mercury in skin had a concentration range of 0.68-3.11 MUg g(-1) dry weight (DW), while Se had a higher concentration range of 74.3-124.5 MUg g(-1) DW. There was no significant correlation between selenium levels in any of the analyzed tissues. Thus, the skin selenium concentration did not reflect the tissular Se levels and did not provide information for biomonitoring. The lack of correlation is explained by the biological role of Se, provided that each tissue regulates Se levels according to physiological needs. However, the skin Hg level had significant positive correlation with the levels in internal tissues (ANOVA p<0.05), particularly with that of muscle (R(2)=0.79; ANOVA p=0.0008). Thus, this correlation permits the estimation of Hg content in muscle based on the multiplication of skin biopsy levels by a factor of 1.85. Mercury bioindication using skin biopsies is a non lethal approach that allows screening of a large number of specimens with little disturbance and makes possible an adequate sampling strategy that produces statistically valid results in populations and study areas. The correlation between Hg levels in the skin and internal tissues supports the use of the epidermis of Commerson's dolphins for Hg biomonitoring in the waters of the Subantarctic, which is a poorly studied region regarding Hg levels, sources and processes. PMID- 26267260 TI - From thought to action: young parents' reasons for participation in parenting support groups at child welfare centers. AB - In this article the focus is on young parents' engagement process in relation to participation in parenting support groups carried out at child welfare centers. This qualitative study focuses not only on young parents' reasons for participating or not participating in parenting support groups during different phases in their engagement process, but also on examining the circumstances that may contribute to such changes. The results show that these reasons can be divided into four categories: the staff, other participants, the social network, and practical circumstances. It also appears that these reasons change between different phases of their engagement process. Primarily three different circumstances contributed to variation in parents' reasons: difficulty in predicting the value of participation, increased closeness in relationships with staff and other parents, and the specific life phase in which young parents find themselves. The results have important implications for policy makers and practitioners in their work in formulating and updating parenting support; they also indicate what may be important to focus on in the recruitment of young parents, and also what may be crucial in regard to them completing their engagement in parent support groups. PMID- 26267262 TI - Severe pain in the fingertip. PMID- 26267261 TI - Molecular systematics of the Cape Parrot (Poicephalus robustus): implications for taxonomy and conservation. AB - The taxonomic position of the Cape Parrot (Poicephalus robustus robustus) has been the focus of much debate. A number of authors suggest that the Cape Parrot should be viewed as a distinct species separate from the other two P. robustus subspecies (P. r. fuscicollis and P. r. suahelicus). These recommendations were based on morphological, ecological, and behavioural assessments. In this study we investigated the validity of these recommendations using multilocus DNA analyses. We genotyped 138 specimens from five Poicephalus species (P. cryptoxanthus, P. gulielmi, P. meyeri, P. robustus, and P. rueppellii) using 11 microsatellite loci. Additionally, two mitochondrial (cytochrome oxidase I gene and 16S ribosomal RNA) and one nuclear intron (intron 7 of the beta-fibrinogen gene) markers were amplified and sequenced. Bayesian clustering analysis and pairwise FST analysis of microsatellite data identified P. r. robustus as genetically distinct from the other P. robustus subspecies. Phylogenetic and molecular clock analyses on sequence data also supported the microsatellite analyses, placing P. r. robustus in a distinct clade separate from the other P. robustus subspecies. Molecular clock analysis places the most recent common ancestor between P. r. robustus and P. r. fuscicollis / P. r. suahelicus at 2.13 to 2.67 million years ago. Our results all support previous recommendations to elevate the Cape Parrot to species level. This will facilitate better planning and implementation of international and local conservation management strategies for the Cape Parrot. PMID- 26267263 TI - Layered Double Hydroxides: Proposal of a One-Layer Cation-Ordered Structure Model of Monoclinic Symmetry. AB - Layered double hydroxides are obtained by partial isomorphous substitution of divalent metal ions by trivalent metal ions in the structure of mineral brucite, Mg(OH)2. The widely reported three-layer polytype of rhombohedral symmetry, designated as polytype 3R1, is actually a one-layer polytype of monoclinic symmetry (space group C2/m, a = 5.401 A, b = 9.355 A, c = 11.02 A, beta = 98.89 degrees ). This structure has a cation-ordered metal hydroxide layer defined by a supercell a = ?3 * a0; b = 3 * a0 (a0 = cell parameter of the cation-disordered rhombohedral cell). Successive layers are translated by (1/3, 0, 1) relative to one another. When successive metal hydroxide layers are translated by (2/3, 0, 1) relative to one another, the resultant crystal, also of monoclinic symmetry, generates a powder pattern corresponding to the polytype hitherto designated as 3R2. This structure model not only removes all the anomalies intrinsic to the widely accepted cation-disordered structure but also abides by Pauling's rule that forbids trivalent cations from occupying neighboring sites and suggests that it is unnecessary to invoke rhombohedral symmetry when the metal hydroxide layer is cation ordered. These results have profound implications for the correct description of polytypism in this family of layered compounds. PMID- 26267264 TI - Trends in the Prevalence of Overweight and Obesity among Chinese Preschool Children from 2006 to 2014. AB - OBJECTIVE: To examine the trends in the prevalence of overweight and obesity among preschool children from 2006 to 2014. METHODS: A total of 145,078 children aged 3-6 years from 46 kindergartens finished the annual health examination in Tianjin, China. Height, weight and other information were obtained using standardized methods. Z-scores for weight, height, and BMI were calculated based on the standards for the World Health Organization (WHO) child growth standards. RESULTS: From 2006 to 2014, mean values of height z-scores significantly increased from 0.34 to 0.54, mean values of weight z-scores kept constant, and mean values of BMI z-scores significantly decreased from 0.40 to 0.23. Mean values of height z-scores, weight z-scores, and BMI z-scores slightly decreased among children from 3 to 4 years old, and then increased among children from 4 to 6 years old. Between 2006 and 2014, there were no significant changes in prevalence of overweight (BMI z-scores >2 SD) and obesity (BMI z-scores >3 SD) among 3-4 years children. However, prevalence of obesity (BMI z-scores >2 SD) increased from 8.8% in 2006 to 10.1% in 2010, and then kept stable until 2014 among 5-6 years children. Boys had higher prevalence of obesity than girls. CONCLUSIONS: Mean values of BMI z-scores decreased from 2006 to 2014 among Chinese children aged 3-6 years old due to the significant increase of height z scores. Prevalence of obesity increased from 2006 to 2010, and then kept stable until 2014 among children aged 5-6 years. The prevalence of obesity was higher in boys than in girls. PMID- 26267265 TI - Effect of Gastric Bypass vs Duodenal Switch on High-Density Lipoprotein Cholesterol Level. PMID- 26267266 TI - Modeling and mapping the probability of occurrence of invasive wild pigs across the contiguous United States. AB - Wild pigs (Sus scrofa), also known as wild swine, feral pigs, or feral hogs, are one of the most widespread and successful invasive species around the world. Wild pigs have been linked to extensive and costly agricultural damage and present a serious threat to plant and animal communities due to their rooting behavior and omnivorous diet. We modeled the current distribution of wild pigs in the United States to better understand the physiological and ecological factors that may determine their invasive potential and to guide future study and eradication efforts. Using national-scale wild pig occurrence data reported between 1982 and 2012 by wildlife management professionals, we estimated the probability of wild pig occurrence across the United States using a logistic discrimination function and environmental covariates hypothesized to influence the distribution of the species. Our results suggest the distribution of wild pigs in the U.S. was most strongly limited by cold temperatures and availability of water, and that they were most likely to occur where potential home ranges had higher habitat heterogeneity, providing access to multiple key resources including water, forage, and cover. High probability of occurrence was also associated with frequent high temperatures, up to a high threshold. However, this pattern is driven by pigs' historic distribution in warm climates of the southern U.S. Further study of pigs' ability to persist in cold northern climates is needed to better understand whether low temperatures actually limit their distribution. Our model highlights areas at risk of invasion as those with habitat conditions similar to those found in pigs' current range that are also near current populations. This study provides a macro-scale approach to generalist species distribution modeling that is applicable to other generalist and invasive species. PMID- 26267267 TI - Imaging Electrogenerated Chemiluminescence at Single Gold Nanowire Electrodes. AB - We report electrogenerated chemiluminescence (ECL) generated at single gold nanowire electrodes supported on tin-doped indium oxide. Unlike other single nanoparticle electrochemical characterization techniques, ECL provides a massively parallel direct readout of electrochemical activity on individual nanoparticle electrodes without the need for extrinsic illumination or a scanning electrochemical probe. While ECL is not observed from as-purchased nanowires due to the surfactant layer, by removing the layer and coating the nanowires with a polymer blend, ECL from single nanowire electrodes is readily measured. With an increase in polymer thickness, an increase in ECL image quality and reproducibility over multiple redox cycles is observed. The polymer coating also provides a strategy for stabilizing gold nanoparticle electrodes against complete surface oxidation in aqueous environments. PMID- 26267268 TI - Genetics of Growth Reaction Norms in Farmed Rainbow Trout. AB - Rainbow trout is farmed globally under diverse uncontrollable environments. Fish with low macroenvironmental sensitivity (ES) of growth is important to thrive and grow under these uncontrollable environments. The ES may evolve as a correlated response to selection for growth in one environment when the genetic correlation between ES and growth is nonzero. The aims of this study were to quantify additive genetic variance for ES of body weight (BW), defined as the slope of reaction norm across breeding environment (BE) and production environment (PE), and to estimate the genetic correlation (rg(int, sl)) between BW and ES. To estimate heritable variance of ES, the coheritability of ES was derived using selection index theory. The BW records from 43,040 rainbow trout performing either in freshwater or seawater were analysed using a reaction norm model. High additive genetic variance for ES (9584) was observed, inferring that genetic changes in ES can be expected. The coheritability for ES was either -0.06 (intercept at PE) or -0.08 (intercept at BE), suggesting that BW observation in either PE or BE results in low accuracy of selection for ES. Yet, the rg(int, sl) was negative (-0.41 to -0.33) indicating that selection for BW in one environment is expected to result in more sensitive fish. To avoid an increase of ES while selecting for BW, it is possible to have equal genetic gain in BW in both environments so that ES is maintained stable. PMID- 26267270 TI - Swelling of Polyelectrolyte Multilayers: The Relation Between, Surface and Bulk Characteristics. AB - The odd-even effect, i.e., the influence of the outermost layer of polyelectrolyte multilayers (PEMs) on their swelling behavior, is investigated. For that purpose poly(styrene sodium sulfonate) (PSS)/poly(diallyl dimethylammonium chloride) (PDADMAC) polyelectrolyte multilayers are studied in air with 1% relative humidity (RH), 30% RH, 95% RH, and in liquid water by ellipsometry, atomic force microscopy (AFM), and X-ray reflectometry (XRR). Since the total amount of water uptake in swollen PEMs is divided into two fractions, the void water and the swelling water, a correct evaluation of the odd-even effect is only possible if both fractions are examined separately. In order to allow measuring samples over a larger thickness regime the investigation of a larger amount of samples is required. Therefore, the concept of separating void water from swelling water using neutron reflectometry is for the first time transferred to ellipsometry. The subsequent analysis of swelling water, void water, and roughness revealed the existence of two types of odd-even effects: an odd-even effect which addresses only the surface of the PEM (surface-odd-even effect) and an odd-even effect which addresses also the bulk of the PEM (bulk-odd even effect). The appearance of both effects is dependent on the environment; the surface-odd-even effect is only detectable in humid air while the bulk-odd-even effect is only detectable in liquid water. The bulk-odd-even effect is related to the osmotic pressure between the PEM and the surrounding water. A correlation between the amount of void water and both odd-even effects is not found. The amount of void water is independent of the terminated layer and the thickness of PEMs. PMID- 26267269 TI - Impact of Selection for Digestive Efficiency on Microbiota Composition in the Chicken. AB - OBJECTIVES: Feed efficiency and its digestive component, digestive efficiency, are key factors in the environmental impact and economic output of poultry production. The interaction between the host and intestinal microbiota has a crucial role in the determination of the ability of the bird to digest its food and to the birds' feed efficiency. We therefore investigated the phenotypic and genetic relationships between birds' efficiency and the composition of the cecal microbiota in a F2 cross between broiler lines divergently selected for their high or low digestive efficiency. METHODS: Analyses were performed on 144 birds with extreme feed efficiency values at 3 weeks, with feed conversion values of 1.41+/-0.05 and 2.02+/-0.04 in the efficient and non-efficient groups, respectively. The total numbers of Lactobacillus, L. salivarius, L. crispatus, C. coccoides, C. leptum and E. coli per gram of cecal content were measured. RESULTS: The two groups mainly differed in larger counts of Lactobacillus, L. salivarius and E. coli in less efficient birds. The equilibrium between bacterial groups was also affected, efficient birds showing higher C. leptum, C. coccoides and L. salivarius to E. coli ratios. The heritability of the composition of microbiota was also estimated and L. crispatus, C. leptum, and C. coccoides to E. coli ratios were moderately but significantly heritable (0.16 to 0.24). The coefficient of fecal digestive use of dry matter was genetically and positively correlated with L. crispatus, C. leptum, C. coccoides (0.50 to 0.76) and negatively with E. coli (-0.66). Lipid digestibility was negatively correlated with E. coli (-0.64), and AMEn positively correlated with C. coccoides and with the C. coccoides to Lactobacillus ratio (0.48 to 0.64). We also detected 14 Quantitative Trait Loci (QTL) for microbiota on the host genome, mostly on C. leptum and Lactobacillus. The QTL for C. leptum on GGA6 was close to genome-wide significance. This region mainly includes genes involved in anti-inflammatory responses and in the motility of the gastrointestinal tract. PMID- 26267271 TI - Antagonist Xist and Tsix co-transcription during mouse oogenesis and maternal Xist expression during pre-implantation development calls into question the nature of the maternal imprint on the X chromosome. AB - During the first divisions of the female mouse embryo, the paternal X-chromosome is coated by Xist non-coding RNA and gradually silenced. This imprinted X inactivation principally results from the apposition, during oocyte growth, of an imprint on the X-inactivation master control region: the X-inactivation center (Xic). This maternal imprint of yet unknown nature is thought to prevent Xist upregulation from the maternal X (X(M)) during early female development. In order to provide further insight into the X(M) imprinting mechanism, we applied single cell approaches to oocytes and pre-implantation embryos at different stages of development to analyze the expression of candidate genes within the Xic. We show that, unlike the situation pertaining in most other cellular contexts, in early growing oocytes, Xist and Tsix sense and antisense transcription occur simultaneously from the same chromosome. Additionally, during early development, Xist appears to be transiently transcribed from the X(M) in some blastomeres of late 2-cell embryos concomitant with the general activation of the genome indicating that X(M) imprinting does not completely suppress maternal Xist transcription during embryo cleavage stages. These unexpected transcriptional regulations of the Xist locus call for a re-evaluation of the early functioning of the maternal imprint on the X-chromosome and suggest that Xist/Tsix antagonist transcriptional activities may participate in imprinting the maternal locus as described at other loci subject to parental imprinting. PMID- 26267272 TI - Alcohol Involvement in Sexual Behaviour and Adverse Sexual Health Outcomes from 26 to 38 Years of Age. AB - BACKGROUND: Research on alcohol and sexual behaviour has focused on young adults or high-risk groups, showing alcohol use contributing to riskier sexual choices. Adults now in their late thirties have been exposed to heavier drinking norms than previously, raising questions about effects on sexual wellbeing. We examined self-reported use and consequences of alcohol in sexual contexts, and its association with usual drinking pattern at age 38, and also associations of heavy drinking occasion (HDO) frequency with number of sexual partners, sexually transmitted infections (STIs), and terminations of pregnancy (TOPs), from 26-32 and 32-38 years of age. METHODS: Members of the Dunedin Study birth cohort answered computer-presented questions about sexual behaviour and outcomes, and interviewer-administered alcohol consumption questions, at age 26, 32 and 38 years. RESULTS: Response level was >90% at each assessment. At 38, drinking before or during sex in the previous year was common (8.2% of men; 14.6% of women reported "usually/always"), and unwanted consequences were reported by 13.5% of men and 11.9% of women, including regretted sex or failure to use contraception or condoms. Frequent heavy drinkers were more likely to "use alcohol to make it easier to have sex" and regret partner choice, particularly women. Heavy drinking frequency was strongly associated with partner numbers for men and women at 32, but only for women at 38. Significantly higher odds of STIs amongst the heaviest drinking men, and TOPs amongst the heaviest drinking women were seen at 32-38. CONCLUSIONS: Alcohol involvement in sex continues beyond young adulthood where it has been well documented, and is common at 38. Women appear to be more affected than men, and heavy drinking is associated with poorer outcomes for both. Improving sexual health and wellbeing throughout the life course needs to take account of the role of alcohol in sexual behaviour. PMID- 26267273 TI - Synergistic Integration of Layer-by-Layer Assembly of Photosensitizer and Gold Nanorings for Enhanced Photodynamic Therapy in the Near Infrared. AB - A layer-by-layer (LbL) assembly strategy was used to incorporate high concentrations of Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) photosensitizer (PS) onto plasmonic Au nanorings (Au NRs) for increasing the cellular uptake of AlPcS4 and subsequently enhancing the efficacy of photodynamic therapy (PDT) of human breast cancer cells (MDA-MB-231) in the near-infrared (NIR) range. Au NRs with two layers of AlPcS4 (Au NR/(AlPcS4)2) markedly increased the cellular internalization of AlPcS4 and elevated the generation of reactive oxygen species (ROS). Quenching the photosensitivity of AlPcS4 on the Au NR surface during the uptake and then significant ROS formation only upon PS release inside the cellular compartment made it possible to achieve a high PDT specificity and efficacy. PDT of breast cancer cells following 4 h of incubation with various formula revealed the following cell destruction rate: ~10% with free AlPcS4, ~23% with singly layered Au NR/(AlPcS4)1 complex, and ~50% with doubly layered Au NR/(AlPcS4)2. Incubation with Au NR/(AlPcS4)2 for an additional 2 h resulted in ~85% cell killing, more than 8-fold increase compared to AlPcS4 alone. Together, integration of LbL of PS with Au NRs holds a significant promise for PDT therapeutic treatment of a variety of cancers. PMID- 26267274 TI - Viral Glycoprotein Complex Formation, Essential Function and Immunogenicity in the Guinea Pig Model for Cytomegalovirus. AB - Development of a cytomegalovirus (CMV) vaccine is a major public health priority due to the risk of congenital infection. A key component of a vaccine is thought to be an effective neutralizing antibody response against the viral glycoproteins necessary for cell entry. Species specificity of human CMV (HCMV) precludes direct studies in an animal model. The guinea pig is the only small animal model for congenital cytomegalovirus infection. Analysis of the guinea pig CMV (GPCMV) genome indicates that it potentially encodes homologs to the HCMV glycoproteins (including gB, gH, gL, gM, gN and gO) that form various cell entry complexes on the outside of the virus: gCI (gB); gCII (gH/gL/gO); gCIII (gM/gN). The gB homolog (GP55) has been investigated as a candidate subunit vaccine but little is known about the other homolog proteins. GPCMV glycoproteins were investigated by transient expression studies which indicated that homolog glycoproteins to gN and gM, or gH, gL and gO were able to co-localize in cells and generate respective homolog complexes which could be verified by immunoprecipitation assays. ELISA studies demonstrated that the individual complexes were highly immunogenic in guinea pigs. The gO (GP74) homolog protein has 13 conserved N-glycosylation sites found in HCMV gO. In transient expression studies, only the glycosylated protein is detected but in virus infected cells both N-glycosylated and non-glycosylated gO protein were detected. In protein interaction studies, a mutant gO that lacked N-glycosylation sites had no impact on the ability of the protein to interact with gH/gL which indicated a potential alternative function associated with these sites. Knockout GPCMV BAC mutagenesis of the respective glycoprotein genes (GP55 for gB, GP75 for gH, GP115 for gL, GP100 for gM, GP73 for gN and GP74 for gO) in separate reactions was lethal for virus regeneration on fibroblast cells which demonstrated the essential nature of the GPCMV glycoproteins. The gene knockout results were similar to HCMV, except in the case of the gO homolog, which was non essential in epithelial tropic virus but essential in lab adapted GPCMV. Overall, the findings demonstrate the similarity between HCMV and GPCMV glycoproteins and strengthen the relevance of this model for development of CMV intervention strategies. PMID- 26267275 TI - Generalization of Auditory Sensory and Cognitive Learning in Typically Developing Children. AB - Despite the well-established involvement of both sensory ("bottom-up") and cognitive ("top-down") processes in literacy, the extent to which auditory or cognitive (memory or attention) learning transfers to phonological and reading skills remains unclear. Most research has demonstrated learning of the trained task or even learning transfer to a closely related task. However, few studies have reported "far-transfer" to a different domain, such as the improvement of phonological and reading skills following auditory or cognitive training. This study assessed the effectiveness of auditory, memory or attention training on far transfer measures involving phonological and reading skills in typically developing children. Mid-transfer was also assessed through untrained auditory, attention and memory tasks. Sixty 5- to 8-year-old children with normal hearing were quasi-randomly assigned to one of five training groups: attention group (AG), memory group (MG), auditory sensory group (SG), placebo group (PG; drawing, painting), and a control, untrained group (CG). Compliance, mid-transfer and far transfer measures were evaluated before and after training. All trained groups received 12 x 45-min training sessions over 12 weeks. The CG did not receive any intervention. All trained groups, especially older children, exhibited significant learning of the trained task. On pre- to post-training measures (test retest), most groups exhibited improvements on most tasks. There was significant mid-transfer for a visual digit span task, with highest span in the MG, relative to other groups. These results show that both sensory and cognitive (memory or attention) training can lead to learning in the trained task and to mid-transfer learning on a task (visual digit span) within the same domain as the trained tasks. However, learning did not transfer to measures of language (reading and phonological awareness), as the PG and CG improved as much as the other trained groups. Further research is required to investigate the effects of various stimuli and lengths of training on the generalization of sensory and cognitive learning to literacy skills. PMID- 26267276 TI - Male Homosexual Preference: Where, When, Why? AB - Male homosexual preference (MHP) has long been of interest to scholars studying the evolution of human sexuality. Indeed, MHP is partially heritable, induces a reproductive cost and is common. MHP has thus been considered a Darwinian paradox. Several questions arise when MHP is considered in an evolutionary context. At what point did MHP appear in the human evolutionary history? Is MHP present in all human groups? How has MHP evolved, given that MHP is a reproductively costly trait? These questions were addressed here, using data from the anthropological and archaeological literature. Our detailed analysis of the available data challenges the common view of MHP being a "virtually universal" trait present in humans since prehistory. The conditions under which it is possible to affirm that MHP was present in past societies are discussed. Furthermore, using anthropological reports, the presence or absence of MHP was documented for 107 societies, allowing us to conclude that evidence of the absence of MHP is available for some societies. A recent evolutionary hypothesis has argued that social stratification together with hypergyny (the hypergyny hypothesis) are necessary conditions for the evolution of MHP. Here, the link between the level of stratification and the probability of observing MHP was tested using an unprecedented large dataset. Furthermore, the test was performed for the first time by controlling for the phylogenetic non-independence between societies. A positive relationship was observed between the level of social stratification and the probability of observing MHP, supporting the hypergyny hypothesis. PMID- 26267279 TI - Fibroblast Growth Factor 2 as a New Approach to Fighting Fear. PMID- 26267277 TI - Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies. AB - The broadly neutralizing HIV monoclonal antibodies (bnMAbs) PG9, PG16, PGT151, and PGT152 have been shown earlier to occasionally display an unusual virus neutralization profile with a non-sigmoidal slope and a plateau at <100% neutralization. In the current study, we were interested in determining the extent of non-sigmoidal slopes and plateaus at <100% for HIV bnMAbs more generally. Using both a 278 panel of pseudoviruses in a CD4 T-cell (U87.CCR5.CXCR4) assay and a panel of 117 viruses in the TZM-bl assay, we found that bnMAbs targeting many neutralizing epitopes of the spike had neutralization profiles for at least one virus that plateaued at <90%. Across both panels the bnMAbs targeting the V2 apex of Env and gp41 were most likely to show neutralization curves that plateaued <100%. Conversely, bnMAbs targeting the high mannose patch epitopes were less likely to show such behavior. Two CD4 binding site (CD4bs) Abs also showed this behavior relatively infrequently. The phenomenon of incomplete neutralization was also observed in a large peripheral blood mononuclear cells (PBMC)-grown molecular virus clone panel derived from patient viral swarms. In addition, five bnMAbs were compared against an 18-virus panel of molecular clones produced in 293T cells and PBMCs and assayed in TZM-bl cells. Examples of plateaus <90% were seen with both types of virus production with no consistent patterns observed. In conclusion, incomplete neutralization and non-sigmoidal neutralization curves are possible for all HIV bnMAbs against a wide range of viruses produced and assayed in both cell lines and primary cells with implications for the use of antibodies in therapy and as tools for vaccine design. PMID- 26267278 TI - One Size Doesn't Fit All - RefEditor: Building Personalized Diploid Reference Genome to Improve Read Mapping and Genotype Calling in Next Generation Sequencing Studies. AB - With rapid decline of the sequencing cost, researchers today rush to embrace whole genome sequencing (WGS), or whole exome sequencing (WES) approach as the next powerful tool for relating genetic variants to human diseases and phenotypes. A fundamental step in analyzing WGS and WES data is mapping short sequencing reads back to the reference genome. This is an important issue because incorrectly mapped reads affect the downstream variant discovery, genotype calling and association analysis. Although many read mapping algorithms have been developed, the majority of them uses the universal reference genome and do not take sequence variants into consideration. Given that genetic variants are ubiquitous, it is highly desirable if they can be factored into the read mapping procedure. In this work, we developed a novel strategy that utilizes genotypes obtained a priori to customize the universal haploid reference genome into a personalized diploid reference genome. The new strategy is implemented in a program named RefEditor. When applying RefEditor to real data, we achieved encouraging improvements in read mapping, variant discovery and genotype calling. Compared to standard approaches, RefEditor can significantly increase genotype calling consistency (from 43% to 61% at 4X coverage; from 82% to 92% at 20X coverage) and reduce Mendelian inconsistency across various sequencing depths. Because many WGS and WES studies are conducted on cohorts that have been genotyped using array-based genotyping platforms previously or concurrently, we believe the proposed strategy will be of high value in practice, which can also be applied to the scenario where multiple NGS experiments are conducted on the same cohort. The RefEditor sources are available at https://github.com/superyuan/refeditor. PMID- 26267283 TI - Corrigendum: Vacancy-controlled ultrastable nanoclusters in nanostructured ferritic alloys. PMID- 26267280 TI - Conflict bear translocation: investigating population genetics and fate of bear translocation in Dachigam National Park, Jammu and Kashmir, India. AB - The Asiatic black bear population in Dachigam landscape, Jammu and Kashmir is well recognized as one of the highest density bear populations in India. Increasing incidences of bear-human interactions and the resultant retaliatory killings by locals have become a serious threat to the survivorship of black bears in the Dachigam landscape. The Department of Wildlife Protection in Jammu and Kashmir has been translocating bears involved in conflicts, henceforth 'conflict bears' from different sites in Dachigam landscape to Dachigam National Park as a flagship activity to mitigate conflicts. We undertook this study to investigate the population genetics and the fate of bear translocation in Dachigam National Park. We identified 109 unique genotypes in an area of ca. 650 km2 and observed bear population under panmixia that showed sound genetic variability. Molecular tracking of translocated bears revealed that mostly bears (7 out of 11 bears) returned to their capture sites, possibly due to homing instincts or habituation to the high quality food available in agricultural croplands and orchards, while only four bears remained in Dachigam National Park after translocation. Results indicated that translocation success was most likely to be season dependent as bears translocated during spring and late autumn returned to their capture sites, perhaps due to the scarcity of food inside Dachigam National Park while bears translocated in summer remained in Dachigam National Park due to availability of surplus food resources. Thus, the current management practices of translocating conflict bears, without taking into account spatio-temporal variability of food resources in Dachigam landscape seemed to be ineffective in mitigating conflicts on a long-term basis. However, the study highlighted the importance of molecular tracking of bears to understand their movement patterns and socio-biology in tough terrains like Dachigam landscape. PMID- 26267284 TI - Spheroid and Tissue Assembly via Click Chemistry in Microfluidic Flow. AB - Proper cell-cell contact and communication are essential for the correct development and survival of higher order organisms. In order to study complex cell interactions that occur in vivo, model systems that are able to recapitulate 3D cell-cell interactions in vitro are key to advancing new biotechnologies, therapeutics, and tissue engineering applications. Herein, we show a new strategy to rapidly and efficiently generate complex multiple cell line containing spheroids and tissues in microfluidic flow without the use of scaffolds, molecular biology, or metabolic biosynthesis. The method relies on the integration of microfluidics, liposome fusion, bio-orthogonal chemistry, and cell surface engineering to rapidly click coculture cell assemblies in flow. We demonstrate this strategy by assembling various combinations of cell types with an interfacial cell to cell click chemistry in microfluidic flow to generate a range of spheroid types and oriented tissue multilayers. PMID- 26267285 TI - Application of Pyrolysis Gas Chromatography in Forensic Science. AB - In this review the range of evidentiary materials that may be successfully examined by pyrolysis gas chromatography is emphasized. Initial sections briefly discuss the main types of commercially available pyrolyzers, i.e., inductively heated devices (Curie point), those employing resistive heating, and furnace pyrolyzers. Sample introduction methods and the effects of various pyrolysis parameters are also considered. Applications to various types of samples, including paint, fibers, rubber and plastic traces, adhesives, photocopy toners, and hair, are then reviewed. PMID- 26267286 TI - Development in the Detection and Identification of Explosive Residues. AB - In the past 2 decades, developments in the sensitivity and selectivity of instrument detectors have significantly improved the detection limits for explosives, particularly nitrated organic compounds. Significant improvements have also been made in clean up and recovery procedures for explosive residues. Methods which also have met the criterion of proven effectiveness in identifying explosive components in "real-world" residues from test explosions have been incorporated into systematic analysis protocols for explosive residues. This article first reviews developments in the application of both traditional and novel methods to analysis of unreacted explosives and explosive residues. Compounds used to formulate commercial, military, and "homemade" explosives are then cross-referenced to the analytical methods that have been specifically applied to them, both as pure chemicals and in explosive mixtures. The subsequent focus is on the combinations of methods used to systematically analyze and positively identify residues from improvised explosive devices, from handswabs derived from persons suspected of handling explosives, and from organic gunshot residue. Technology is available to positively identify virtually any unreacted explosive in residue, but no one method can detect all components of all explosives. Investigators and the courts are best served by well-equipped forensic science laboratories staffed with scientists who have gained experience by the successful analysis of post-blast residues from an explosives range and have comprehensive reference collections of physical material, analytical data, and literature. The greatest progress has been made with respect to nitrated organic compounds, but the new generation of commercial explosive slurries and emulsions which are primarily formulated with inorganic salts and non-nitrated organic compounds offer an ongoing challenge. PMID- 26267287 TI - Important Considerations in the Interpretation of Forensic Urine Drug Test Results. AB - With sound analytical methodology, good laboratory practice, and intact specimen chain-of-custody, test result interpretation is the final element dictating the action to be taken following drug urinalysis. From a technical viewpoint, false test results may be reported as a result of adulteration, including the alteration of metabolic process through the intentional use of foreign material, or the outright addition of adulterants to specimens. Unintended exposure through contact or inhalation may result in the detection of targeted drug analytes at low levels, while the use of certain licit food and medicinal items, such as a salad dressing, a bagel containing poppy seeds, and Tylenol(r) III, may produce positive results using commonly reporting cutoff levels. For those specimens that test positively, the following factors should be considered when interpreting the meaning of a quantitative result: analyte stability, urine water content, and time lapse between drug exposure and specimen collection. PMID- 26267288 TI - Recovery and Stability of DNA in Samples of Forensic Science Significance. AB - The ability to recover sufficient amounts of deoxyribonucleic acid (DNA) from various biological evidentiary samples for individualization purposes is discussed. The chemistry and stability of DNA under various conditions is reviewed. The recovery of nondegraded DNA bears directly on the ability to successfully analyze such samples by restriction fragment length polymorphism analysis, as well as by methods utilizing the polymerase chain reaction (PCR), which includes (1) reverse dot-blot hybridization using allele-specific oligonucleotide probes and (2) allele-specific fragment length polymorphism analysis, steroids with A-ring modifications, steroids with an extra ring, and steroids with B-ring and C-ring modifications. Common metabolic pathways are noted and summarized. PMID- 26267289 TI - Nanosized ethosomes-based hydrogel formulations of methoxsalen for enhanced topical delivery against vitiligo: formulation optimization, in vitro evaluation and preclinical assessment. AB - The present investigation aimed for the development and characterization of ethosomes-based hydrogel formulations of methoxsalen for enhanced topical delivery and effective treatment against vitiligo. The ethosomes were prepared by central composite design (CCD) and characterized for various quality attributes like vesicle shape, size, zeta potential, lamellarity, drug entrapment and drug leaching. The optimized ethosomes were subsequently incorporated int Carbopol(r) 934 gel and characterized for drug content, rheological behavior, texture profile, in vitro release, ex vivo skin permeation and retention, skin photosensitization and histopathological examination. Ethosomes were found to be spherical and multilamellar in structures having nanometric size range with narrow size distribution, and high encapsulation efficiency. Ethosomal formulations showed significant skin permeation and accumulation in the epidermal and dermal layers. The fluorescence microscopy study using 123 Rhodamine exhibited enhanced permeation of the drug-loaded ethosomes in the deeper layers of skin. Also, the developed formulation showed insignificant phototoxicity and erythema vis-a-vis the conventional cream. The results were cross-validated using histopathological examination of skin segments. In a nutshell, the ethosomes based hydrogel formulation was found to be a promising drug delivery system demonstrating enhanced percutaneous penetration of methoxsalen with reduced phototoxicity and erythema, thus leading to improved patient compliance for the treatment against vitiligo. PMID- 26267290 TI - Quantum-Chemical Calculation of Carbododecahedron Formation in Carbon Plasma. AB - The ground state of the molecule consisting of 10 carbon atoms in C10(rg) "ring" conformation and the energy of its metastable C10(st) "star" conformation are reported. The reaction coordinate for the isomeric transition C10(st) -> C10(rg) was calculated using density functional theory (DFT) with UB3LYP/6-31G(d,p). It was established that a 5-fold symmetry axis is conserved in this isomeric transition. The total energy of the ring isomer is by 10.33 eV (9.16 eV as zero point energy corrected) lower than that of the star isomer. The energy barrier for the transition from the metastable star state to the ring state is 2.87 eV (3.57 eV as zero-point energy corrected). An analysis of possible chemical reactions in carbon plasma involving C10(st) and C10(rg) and leading to the formation of C20 fullerenes was performed. It was revealed that the presence of the C10(st) conformation in the reaction medium is a necessary condition for C20 fullerene formation. It was shown that the presence of hydrogen atoms in carbon plasma and UV radiation accelerate the C10(st) -> C10(rg) transition and thus suppress the C20 fullerene formation. PMID- 26267291 TI - Liver receptor homolog-1 is a critical determinant of methyl-pool metabolism. AB - Balance of labile methyl groups (choline, methionine, betaine, and folate) is important for normal liver function. Quantitatively, a significant use of labile methyl groups is in the production of phosphatidylcholines (PCs), which are ligands for the nuclear liver receptor homolog-1 (LRH-1). We studied the role of LRH-1 in methyl-pool homeostasis and determined its metabolic effects using the methionine and choline-deficient (MCD) diet, which depletes methyl groups and results in a deleterious decrease in the PC-to-phosphatidylethanolamine ratio. We found that MCD diet-fed, liver-specific LRH-1 knockout mice (Lrh-1(-/-) ) do not show the expected decreased methyl-pool and PC/phosphatidylethanolamine ratio and are resistant to the hepatitis and fibrosis normally induced by the diet. Adaptive responses observed in wild-type mice on the MCD diet were also observed in Lrh-1(-/-) mice on a normal diet. This includes reduced expression of the highly active glycine-n-methyltransferase and the biliary phospholipid floppase multidrug-resistance protein 2 (Mdr2/Abcb4), resulting in reduced consumption of methyl groups and biliary PC secretion. In vitro studies confirm that Gnmt and Mdr2 are primary LRH-1 target genes. Additional similarities between hepatic gene expression profiles in MCD diet-fed wild-type and untreated Lrh-1(-/-) mice suggest that methyl-pool deficiency decreases LRH-1 activity, and this was confirmed by in vitro functional results in cells maintained in MCD medium. CONCLUSION: LRH-1 is a novel transcriptional regulator of methyl-pool balance; when the methyl-pool is depleted, decreased LRH-1 transactivation suppresses expression of key genes to minimize loss of labile methyl groups. (Hepatology 2016;63:95-106). PMID- 26267292 TI - Sedative and cardiopulmonary effects of xylazine alone or in combination with methadone, morphine or tramadol in sheep. AB - OBJECTIVE: To evaluate the cardiopulmonary and sedative effects of xylazine alone or in combination with methadone, morphine or tramadol in sheep. STUDY DESIGN: Experimental, prospective, crossover, randomized, blinded study. ANIMALS: Six Santa Ines breed sheep (females) aged 12 +/- 8 months and weighing 39.5 +/- 7.4 kg. METHODS: Sheep were sedated with each of four treatments in a randomized, crossover design, with a minimum washout period of 7 days between treatments. Treatments were: X [xylazine (0.1 mg kg(-1))]; XM [xylazine (0.1 mg kg(-1)) and methadone (0.5 mg kg(-1))]; XMO [xylazine (0.1 mg kg(-1)) and morphine (0.5 mg kg(-1))], and XT [xylazine (0.1 mg kg(-1)) and tramadol (5 mg kg(-1))]. Each drug combination was mixed in the syringe and injected intravenously. Sedation, heart rate (HR), mean arterial blood pressure (MAP), rectal temperature (RT degrees C), respiratory rate (fR), arterial blood gases and electrolytes were measured before drug administration (T0) and then at 15 minute intervals for 120 minutes (T15 T120). RESULTS: Heart rate significantly decreased in all treatments compared with T0. PaCO2 values in XM and XMO were higher at all time points compared with T0. In treatments X and XM, pH, bicarbonate (HCO3-) and base excess were increased at all time points compared with T0. PaO2 was significantly decreased at T15-T75 in XM, at all time points in XMO, and at T15 and T30 in XT. Sedation at T15 and T30 in XM and XMO was greater than in the other treatments. CONCLUSIONS AND CLINICAL RELEVANCE: The combinations of methadone, morphine or tramadol with xylazine resulted in cardiopulmonary changes similar to those induced by xylazine alone in sheep. The combinations provided better sedation, principally at 15 minutes and 30 minutes following administration. PMID- 26267294 TI - The Mechanism of Iron(II)-Catalyzed Asymmetric Mukaiyama Aldol Reaction in Aqueous Media: Density Functional Theory and Artificial Force-Induced Reaction Study. AB - Density functional theory (DFT), combined with the artificial force-induced reaction (AFIR) method, is used to establish the mechanism of the aqueous Mukaiyama aldol reactions catalyzed by a chiral Fe(II) complex. On the bases of the calculations, we identified several thermodynamically stable six- or seven coordinate complexes in the solution, where the high-spin quintet state is the ground state. Among them, the active intermediates for the selectivity determining outer-sphere carbon-carbon bond formation are proposed. The multicomponent artificial force-induced reaction (MC-AFIR) method found key transition states for the carbon-carbon bond formation, and explained the enantioselectivity and diastereoselectivity. The overall mechanism consists of the coordination of the aldehyde, carbon-carbon bond formation, the rate determining proton transfer from water to aldehyde, and dissociation of trimethylsilyl group. The calculated full catalytic cycle is consistent with the experiments. This study provides important mechanistic insights for the transition metal catalyzed Mukaiyama aldol reaction in aqueous media. PMID- 26267293 TI - FTY720 and two novel butterfly derivatives exert a general anti-inflammatory potential by reducing immune cell adhesion to endothelial cells through activation of S1P(3) and phosphoinositide 3-kinase. AB - Sphingosine-1-phosphate (S1P) is a key lipid regulator of a variety of cellular responses including cell proliferation and survival, cell migration, and inflammatory reactions. Here, we investigated the effect of S1P receptor activation on immune cell adhesion to endothelial cells under inflammatory conditions. We show that S1P reduces both tumor necrosis factor (TNF)-alpha- and lipopolysaccharide (LPS)-stimulated adhesion of Jurkat and U937 cells to an endothelial monolayer. The reducing effect of S1P was reversed by the S1P1+3 antagonist VPC23019 but not by the S1P1 antagonist W146. Additionally, knockdown of S1P3, but not S1P1, by short hairpin RNA (shRNA) abolished the reducing effect of S1P, suggesting the involvement of S1P3. A suppression of immune cell adhesion was also seen with the immunomodulatory drug FTY720 and two novel butterfly derivatives ST-968 and ST-1071. On the molecular level, S1P and all FTY720 derivatives reduced the mRNA expression of LPS- and TNF-alpha-induced adhesion molecules including ICAM-1, VCAM-1, E-selectin, and CD44 which was reversed by the PI3K inhibitor LY294002, but not by the MEK inhibitor U0126.In summary, our data demonstrate a novel molecular mechanism by which S1P, FTY720, and two novel butterfly derivatives acted anti-inflammatory that is by suppressing gene transcription of various endothelial adhesion molecules and thereby preventing adhesion of immune cells to endothelial cells and subsequent extravasation. PMID- 26267295 TI - The performance of methallyl nickel complexes and boron adducts in the catalytic activation of ethylene: a conceptual DFT perspective. AB - In this work, global and local descriptors of chemical reactivity and selectivity are used to explain the differences in reactivities toward ethylene of methallyl nickel complexes and their B(C6F5)3 and BF3 adducts. DFT calculations were used to explain why nickel complexes alone are inactive in ethylene polymerization while their boron adducts can activate it. It is shown that chemical potential, hardness, electrophilicity and molecular electrostatic potential surfaces describe fairly well the reactivity and selectivity of these organometallic systems toward ethylene. Experimental data indicates that addition of a borane molecule to nickel complexes changes dramatically their reactivity-behavior that is confirmed computationally. Our results show that bare complexes are unable to activate ethylene-a Lewis base-because they also behave as Lewis bases. The addition of the co-catalyst-a Lewis acid-turns the adducts into Lewis acids, making them active towards ethylene. PMID- 26267296 TI - Interaction of YD2 and TiO2 in dye-sensitized solar cells (DSSCs): a density functional theory study. AB - The interaction of the dye YD2 with a cluster of (anatase-phase) TiO2 (which is utilized in dye-sensitized solar cells, DSSCs) and electron injection by the dye into the cluster were studied by performing density functional theory (DFT) calculations at the B3LYP, PBE, and TPSS levels of theory, including dispersion effects. We studied and quantified the interaction of the metallomacrocycle with the TiO2 cluster and the electronic spectrum of the complex. TDDFT calculations using the B3LYP functional were found to be the most suitable for describing the observed absorption energy bands of YD2 and YD2-TiO2. Our calculations show that the diarylamino groups act as electron donors in the photon-induced injection that occurs in DSSCs. The free-energy changes that take place during electron injection support the good performance of YD2 on TiO2 clusters. PMID- 26267297 TI - A comparative molecular dynamics study of thermophilic and mesophilic beta fructosidase enzymes. AB - Arabidopsis thaliana cell wall invertase 1 (AtcwINV1) and Thermotoga maritima beta-fructosidase (BfrA) are among the best structurally studied members of the glycoside hydrolase family 32. Both enzymes hydrolyze sucrose as the main substrate but differ strongly in their thermal stability. Mesophilic AtcwINV1 and thermophilic BfrA have divergent sequence similarities in the N-terminal five bladed beta-propeller catalytic domain (31 %) and the C-terminal beta-sandwich domain (15 %) of unknown function. The two enzymes were subjected to 200 ns molecular dynamics simulations at 300 K (27 degrees C) and 353 K (80 degrees C). Regular secondary structure regions, but not loops, in AtcwINV1 and BfrA showed no significant fluctuation differences at both temperatures. BfrA was more rigid than AtcwINV1 at 300 K. The simulation at 353 K did not alter the structural stability of BfrA, but did increase the overall flexibility of AtcwINV1 exhibiting the most fluctuating regions in the beta-propeller domain. The simulated heat treatment also increased the gyration radius and hydrophobic solvent accessible surface area of the plant enzyme, consistent with the initial steps of an unfolding process. The preservation of the conformational rigidity of BfrA at 353 K is linked to the shorter size of the protein loops. Shortening of BfrA loops appears to be a key mechanism for thermostability. PMID- 26267299 TI - Catalytic mechanisms of Au11 and Au11-nPt n (n=1-2) clusters: a DFT investigation on the oxidation of CO by O2. AB - The oxidation of CO catalyzed by clusters of Au11, Au10Pt and Au9Pt2 was investigated using the M06 functional suite of the density functional theory. Au and Pt atoms were described with the double-zeta valence basis set Los Alamos National Laboratory 2-double-z (LanL2DZ), whereas the standard 6-311++G(d,p) basis set was employed for the C and O atoms. Our theoretical model showed that (1) after coordination to Au and Au-Pt cluster, O2 and CO are apparently activated, and Mulliken charges show that the gold atoms in the active sites of Au11 are negatively charged; (2) Au-Pt clusters with 11 atoms can effectively catalyze the oxidation of CO by O2; (3) Au11 exhibits good catalytic performance for the oxidation of CO; (4) oxidation of CO occurs preferably on the Au-Pt active sites in Pt-doped clusters, and the single-center mechanisms are more favorable energetically than the two-center mechanisms; (5) after adsorption, an O2 molecule oxidates two CO molecules via stepwise mechanisms; and (6) the catalytic processes are highly exothermic. PMID- 26267298 TI - Computational design, functional analysis and antigenic epitope estimation of a novel hybrid of 12 peptides of hirudin and reteplase. AB - Cardiovascular and cerebrovascular diseases are leading causes of morbidity and mortality for human beings, and thrombosis is the major risk factor. Thrombolytic therapy has been testified to be the most effective approach to cure thrombosis related diseases. In clinical treatment, we often adopt a combination therapeutic regimen of both thrombolytic and anticoagulant agents to prevent the recurrence of thrombosis. Thus, a novel hybrid (HV12p-rPA) comprised of the C-terminal 12 residues of hirudin-PA (HV12p) and reteplase (rPA) was designed. The three dimensional structure of this hybrid was mimicked based on homology modeling and refined with dynamics simulation by utilizing Amber12.0 software. The function of the hybrid was analyzed by structure comparison and the root mean square deviation (RMSD) of Calpha atoms between the hybrid and native rPA was calculated. The results showed that HV12p, which was located in the N-terminus of the hybrid, was far from the rPA segment of the hybrid and had no influence on the conformational stability of the rPA domain. The RMSD of Calpha atoms of these superimposed proteins was about 40A, implying that the hybrid had a similar spatial conformation to that of native rPA. Additionally, the antigenic epitopes of the hybrid were predicted by estimations of Hopp-Wood hydrophilicity, Janin accessibility, Zimmermane-Simha polarity, Bhaskaran-Ponnuswamy flexibility, as well as secondary structure analysis and Kolaskar-Tongaonkar antigenicity prediction. The results showed that the most likely antigenic determinants were located at or near regions 148-152, 257-262 and 321-330. PMID- 26267300 TI - Water-soluble Ir(iii) complexes of deprotonated N-methylbipyridinium ligands: fluorine-free blue emitters. AB - New blue or blue-green emitting iridium complexes have been synthesised with cyclometalating ligands derived from the 1-methyl-3-(2'-pyridyl)pyridinium cation. Efficient luminescence is observed in MeCN or aqueous solutions, with a large range of lifetimes in the MUs region and relatively high quantum yields. PMID- 26267301 TI - Profiling stainless steel welding processes to reduce fume emissions, hexavalent chromium emissions and operating costs in the workplace. AB - Nine gas metal arc welding (GMAW) processes for stainless steel were assessed for fume generation rates, fume generation rates per g of electrode consumed, and emission rates for hexavalent chromium (Cr(6+)). Elemental manganese, nickel, chromium, iron emissions per unit length of weld, and labor plus consumables costs were similarly measured. Flux-cored arc welding and shielded metal arc (SMAW) processes were also studied. The objective was to identify the best welding processes for reducing workplace exposures, and estimate costs for all processes. Using a conical chamber, fumes were collected, weighed, recovered, and analyzed by inductively coupled atomic emission spectroscopy for metals, and by ion chromatography for Cr(6+). GMAW processes used were Surface Tension Transfer, Regulated Metal Deposition, Cold Metal Transfer, short-circuit, axial spray, and pulsed spray modes. Flux-cored welding used gas shielding; SMAW used E308 rods. Costs were estimated as dollars per m length of a 1/4 in (6.3 mm) thick horizontal butt weld; equipment costs were estimated as ratios of new equipment costs to a 250 ampere capacity SMAW welding machine. Results indicate a broad range of fume emission factors for the processes studied. Fume emission rates per g of electrode were lowest for GMAW processes such as pulsed-spray mode (0.2 mg/g), and highest for SMAW (8 mg fume/g electrode). Emission rates of Cr(6+) ranged from 50-7800 ug/min, and Cr(6+) generation rates per g electrode ranged from 1-270 ug/g. Elemental Cr generation rates spanned 13-330 ug/g. Manganese emission rates ranged from 50-300 ug/g. Nickel emission rates ranged from 4-140 ug/g. Labor and consumables costs ranged from $3.15 (GMAW pulsed spray) to $7.40 (SMAW) per meter of finished weld, and were measured or estimated for all 11 processes tested. Equipment costs for some processes may be as much as five times the cost of a typical SMAW welding machine. The results show that all of the GMAW processes in this study can substantially reduce fume, Cr(6+), manganese and costs relative to SMAW, the most commonly used welding process, and several have exceptional capabilities for reducing emissions. PMID- 26267302 TI - Wetting of Surfaces Made of Hydrophobic Cavities. AB - Templated electrodeposition through a close packed, monolayer array of 3 MUm polystyrene spheres followed by removal of the template by dissolution in an organic solvent was used to fabricate sphere segment void (SSV) surfaces in gold with heights up to 1.5 MUm. These surfaces were made hydrophobic by treating with 1-dodecanethiol. Contact angle measurements show that the wetting behavior of these surfaces change significantly with film thickness. The apparent advancing contact angle increases from 110 degrees for the flat 1-dodecanethiol-coated gold surface to 150 degrees for the film with a close-packed array of hemispherical cavities, in good agreement with the behavior predicted by the simple Cassie-Baxter equation. In contrast, the apparent receding angles have significantly smaller values in all cases, and water droplets are strongly pinned at the surface. Thus, these surfaces demonstrate "rose petal" behavior, in which a large apparent advancing contact angle, typical of a superhydrophobic surface, is accompanied by significant contact angle hysteresis. Observation of the shapes of drops on the surface during evaporation-driven recession shows that the drops adopt a dodecagonal shape, in which the drop perimeter is selectively pinned along the ?10? and ?11? directions on the hexagonally close-packed surface. PMID- 26267304 TI - Hypothalamic-pituitary sarcoidosis with vision loss and hypopituitarism: case series and literature review. AB - PURPOSE: Hypothalamic-pituitary (HP) neurosarcoidosis (NS) accounts for 0.5 % cases of sarcoidosis and 1 % of HP masses. Correlative data on endocrine and neurological outcomes is lacking. METHODS: Retrospective case series and literature review of presentation, treatment and outcome of HP NS. RESULTS: Our series includes 4 men, ages 34-59, followed for a median of 7.3 years (range 1.5 17). All had optic neuropathy, multiple pituitary hormone abnormalities (PHAs) and other organ involvement by sarcoidosis (lung, sino-nasal, brain/spine and facial nerve). Two patients had central diabetes insipidus and one impaired thirst with polydipsia. After treatment with high-dose glucocorticoids, optic neuropathy improved in one case and stabilized in the others. After treatment, HP lesions improved radiologically, but PHAs persisted in all cases. Review of four published series on HP NS in addition to ours yielded 46 patients, age 37 +/- 11.8 years, 65 % male. PHAs consisted of anterior hypopituitarism (LH/FSH 88.8 %, TSH 67.4 %, GH 50.0 %, ACTH 48.8 %), hyperprolactinemia (48.8 %) and diabetes insipidus (65.2 %). PHAs were the first sign of disease in 54.3 % patients. Vision problems occurred in 28.3 % patients, but optic neuropathy was not well documented in previous series. Most patients (93.5 %) received high-dose glucocorticoids followed by taper; 50 % also received other immunomodulators, including methotrexate, mycophenolate mofetil, cyclosporine, azathioprine, infliximab and hydrochloroquine. Only 13 % patients showed improvement in PHAs. All-cause mortality was 8.7 %. CONCLUSION: HP NS is a serious disease requiring multidisciplinary treatment and lifelong follow-up. Prospective multicentric studies are needed to determine a more standardized approach to HP NS and outline predictors of disease outcome. PMID- 26267303 TI - Extended transsphenoidal approach for pituitary adenomas invading the cavernous sinus using multiple complementary techniques. AB - PURPOSE: Transsphenoidal surgery is the treatment of choice for most pituitary adenomas (PA), except prolactinomas. Difficulties achieving radical resection with this method are encountered in patients with PAs invading the cavernous sinus (CS), due to the inability of the standard transsphenoidal approach to expose all tumors adequately. This study analyzed methods to resect PAs invading the CS and factors influencing the degree of tumor resection and occurrence of complications. METHODS: Outcomes were retrospectively analyzed in 52 patients with PA invading the CS who underwent surgery via the extended transsphenoidal approach utilizing multiple techniques, including microscopy, endoscopy, neuronavigation, and intraoperative Doppler ultrasonography. RESULTS: Gross-total resection (GTR) was achieved in 33 patients (63.5 %). GTR rate was significantly higher in patients with Knosp Grade 3 than Knosp Grade 4 (92.3 vs. 53.8 %) and in patients undergoing initial surgery than reoperation (77.1 vs. 35.3 %). One patient (2.9 %) undergoing initial surgery experienced transient cranial nerve palsy, without other postoperative complications. Postoperative complications were significantly higher after reoperation. Firm tumor consistency was significantly more frequent in patients undergoing reoperation than initial surgery (52.9 vs. 8.6 %). CONCLUSION: Extended transsphenoidal surgery incorporating multiple complementary techniques was highly effective for PAs invading the CS. Postoperative complications rates were relatively low, especially for patients undergoing initial surgery and those with Knosp Grade 3 tumors. Total resection of PAs invading the CS remains challenging, especially in patients undergoing reoperation or having firm tumors. PMID- 26267305 TI - Anatomical variations of the celiac trunk: cadaveric and radiological study. AB - PURPOSE: The celiac trunk (CT) is a vascular structure of the upper abdomen which gives off the left gastric artery (LGA), the splenic artery and the common hepatic artery. This study aims to compare the vascular patterns of the CT of two different samples (cadaveric and radiological) and to propose a simple classification of CT variations based on previous studies and our results. MATERIALS AND METHODS: To perform this study we examined 43 adult cadavers, 24 males and 19 females, ages ranged from 69 to 92. In addition, we analysed 596 MDCT (multidetector computed tomographic) angiography examinations of 430 males and 166 females, ages ranged from 42 to 82. RESULTS: According to the classification proposed, results were divided into Type I or complete CT (578/639 cases, 90.5 %), Type II or incomplete CT (61/639 cases, 9.5 %), Type III or absence of CT and Type IV or celiacomesenteric trunk with no cases reported. Type I was divided into Type Ia or bifurcated trunk with LGA arising first (368/639 cases, 57.6 %), Type Ib or trifurcated trunk (205/639 cases, 32.1 %) and Type Ic or tetrafurcated trunk with an extra branch (5/639 cases, 0.8 %). Type II included hepatosplenic (29/639 cases, 4.5 %), gastroplenic (32/639, 5 %) and hepatogastric trunks (0/639, 0 %) which represented Types IIa, IIb and IIc respectively. CONCLUSIONS: No significant differences were found between the cadaveric and radiological samples. Gender did not appear to be related to any variability of the structures either. A new, simple and complete classification of the anatomical variations of the CT is proposed. PMID- 26267307 TI - Reduced matrix rigidity promotes neonatal cardiomyocyte dedifferentiation, proliferation and clonal expansion. AB - Cardiomyocyte (CM) maturation in mammals is accompanied by a sharp decline in their proliferative and regenerative potential shortly after birth. In this study, we explored the role of the mechanical properties of the underlying matrix in the regulation of CM maturation. We show that rat and mouse neonatal CMs cultured on rigid surfaces exhibited increased myofibrillar organization, spread morphology, and reduced cell cycle activity. In contrast, compliant elastic matrices induced features of CM dedifferentiation, including a disorganized sarcomere network, rounding, and conspicuous cell-cycle re-entry. The rigid matrix facilitated nuclear division (karyokinesis) leading to binucleation, while compliant matrices promoted CM mitotic rounding and cell division (cytokinesis), associated with loss of differentiation markers. Moreover, the compliant matrix potentiated clonal expansion of CMs that involves multiple cell divisions. Thus, the compliant microenvironment facilitates CM dedifferentiation and proliferation via its effect on the organization of the myoskeleton. Our findings may be exploited to design new cardiac regenerative approaches. PMID- 26267308 TI - Difluorenyl carbo-Benzenes: Synthesis, Electronic Structure, and Two-Photon Absorption Properties of Hydrocarbon Quadrupolar Chromophores. AB - The synthesis, crystal and electronic structures, and one- and two-photon absorption properties of two quadrupolar fluorenyl-substituted tetraphenyl carbo benzenes are described. These all-hydrocarbon chromophores, differing in the nature of the linkers between the fluorenyl substituents and the carbo-benzene core (C-C bonds for 3 a, C-C=C-C expanders for 3 b), exhibit quasi-superimposable one-photon absorption (1PA) spectra but different two-photon absorption (2PA) cross-sections sigma2PA. Z-scan measurements (under NIR femtosecond excitation) indeed showed that the C=C expansion results in an approximately twofold increase in the sigma2PA value, from 336 to 656 GM (1 GM = 10(-50) cm(4) s molecule(-1) photon(-1)) at lambda = 800 nm. The first excited states of Au and Ag symmetry accounting for 1PA and 2PA, respectively, were calculated at the TDDFT level of theory and used for sum-over-state estimations of sigma2PA(lambdai), in which lambdai = 2 hc/Ei, h is Planck's constant, c is the speed of light, and Ei is the energy of the 2PA-allowed transition. The calculated sigma2PA values of 227 GM at 687 nm for 3 a and 349 GM at 708 nm for 3 b are in agreement with the Z-scan results. PMID- 26267306 TI - Aven recognition of RNA G-quadruplexes regulates translation of the mixed lineage leukemia protooncogenes. AB - G-quadruplexes (G4) are extremely stable secondary structures forming stacks of guanine tetrads. DNA G4 structures have been extensively studied, however, less is known about G4 motifs in mRNAs, especially in their coding sequences. Herein, we show that Aven stimulates the mRNA translation of the mixed lineage leukemia (MLL) proto-oncogene in an arginine methylation-dependent manner. The Aven RGG/RG motif bound G4 structures within the coding regions of the MLL1 and MLL4 mRNAs increasing their polysomal association and translation, resulting in the induction of transcription of leukemic genes. The DHX36 RNA helicase associated with the Aven complex and was required for optimal translation of G4 mRNAs. Depletion of Aven led to a decrease in synthesis of MLL1 and MLL4 proteins resulting in reduced proliferation of leukemic cells. These findings identify an Aven-centered complex that stimulates the translation of G4 harboring mRNAs, thereby promoting survival of leukemic cells. PMID- 26267309 TI - Impact of Human Rhinovirus Types and Viral Load on the Severity of Illness in Hospitalized Children With Lower Respiratory Tract Infections. AB - BACKGROUND: Human rhinovirus (HRV) is not only responsible for at least one-half of all common colds but also associated with bronchitis, bronchiolitis, pneumonia and acute asthma exacerbation. However, the impact of different HRV types and viral load on disease severity has not been thoroughly elucidated. METHODS: From January 2012 to September 2014, 1742 nasopharyngeal aspirate specimens from hospitalized children with lower respiratory tract infections were analyzed by quantitative HRV-specific real-time polymerase chain reaction. RESULTS: Among these 1742 children, HRV (407/1742, 23%) was the second most common viral agent after respiratory syncytial virus. HRV-A, HRV-B, HRV-C and HRV untyped were detected in 229 (56%), 27 (7%), 100 (25%) and 51 (13%) specimens, respectively. Children except who experienced wheezing were more common in the HRV-C detection group than in the HRV-A detection group; there were no other significant differences between the 2 groups, including the percent of children diagnosed with severe diseases. Logistic regression models demonstrated that there was no difference in disease severity among HRV types. In HRV-A detection group, in children younger than 2 years, the viral load was higher in the severe group than in the nonsevere group; but in the HRV-C detection group, there was no difference. CONCLUSIONS: HRV was frequently present in hospitalized children with lower respiratory tract infections in Chongqing, China. The disease severity for HRV-C and HRV-A was similar. A high load of HRV-A in the lower respiratory tract might be connected with disease severity in children younger than 2 years. PMID- 26267310 TI - Etiology and Incidence of Pleural Empyema in South African Children. AB - BACKGROUND: South Africa introduced the 7-valent pneumococcal conjugate vaccine (PCV7) in 2009 and PCV13 in 2011. The etiology and incidence of childhood empyema in an 8-year period overlapping the introduction of PCV was investigated. METHODS: Children younger than 12 years admitted with empyema at a tertiary pediatric hospital in Cape Town, South Africa, from December 2006 to December 2011 (cohort A) and January 2012 to December 2014 (cohort B) were investigated. Pathogens were identified by culture of pleural fluid and blood. In addition, polymerase chain reaction targeting bacterial pathogens and Streptococcus pneumoniae serotypes was conducted on pleural fluid in a subset of patients enrolled 2009-2011. RESULTS: Cohort A: 142 children were prospectively enrolled, with a median age of 17 months (interquartile range 8-43). Most (92%) children were unimmunized with PCV. S. pneumoniae and Staphylococcus aureus were the most common culture-identified pathogens (each 25 of 142; 18%); polymerase chain reaction of pleural fluid increased yield of S. pneumoniae detection by 31% [26 of 54 (48%) vs. 9 of 54 (17%), P < 0.001]. Serotypes were identified for 24 of 26 (92%) patients with S. pneumoniae, of which 22 of 24 (92%) were included in PCV13. Cohort B: 22 patients were retrospectively identified. No pathogen was found in 12 of 22 (54.5%) patients and S. pneumoniae in 1 patient (4.5%). Empyema incidence declined by 50% in cohort B compared with that of cohort A (4.2 vs. 10.4 cases per 1000 pneumonia admissions; risk ratio: 0.5; 95% confidence incidence: 0.3-0.7). CONCLUSION: S. pneumoniae is the commonest cause of childhood empyema in South Africa. PCV has been highly effective at reducing empyema incidence in South African children. PMID- 26267311 TI - Understanding the lateral dose response functions of high-resolution photon detectors by reverse Monte Carlo and deconvolution analysis. AB - The purpose of the present study is to understand the mechanism underlying the perturbation of the field of the secondary electrons, which occurs in the presence of a detector in water as the surrounding medium. By means of 'reverse' Monte Carlo simulation, the points of origin of the secondary electrons contributing to the detector's signal are identified and associated with the detector's mass density, electron density and atomic composition. The spatial pattern of the origin of these secondary electrons, in addition to the formation of the detector signal by components from all parts of its sensitive volume, determines the shape of the lateral dose response function, i.e. of the convolution kernel K(x,y) linking the lateral profile of the absorbed dose in the undisturbed surrounding medium with the associated profile of the detector's signal. The shape of the convolution kernel is shown to vary essentially with the electron density of the detector's material, and to be attributable to the relative contribution by the signal-generating secondary electrons originating within the detector's volume to the total detector signal. Finally, the representation of the over- or underresponse of a photon detector by this density dependent convolution kernel will be applied to provide a new analytical expression for the associated volume effect correction factor. PMID- 26267312 TI - Not the Last Word: Choosing Wisely. PMID- 26267313 TI - Threat processing: models and mechanisms. AB - The experience of fear is closely linked to the survival of species. Fear can be conceptualized as a brain state that orchestrates defense reactions to threats. To avoid harm, an organism must be equipped with neural circuits that allow learning, detecting, and rapidly responding to threats. Past experience with threat can transform neutral stimuli present at the time of experience into learned threat-related stimuli via associative learning. Pavlovian threat conditioning is the central experimental paradigm to study associative learning. Once learned, these stimulus-response associations are not always expressed depending on context or new experiences with the conditioned stimuli. Neural circuits mediating threat learning have the inherent plasticity to adapt to changing environmental threats. Encounters devoid of danger pave the way for extinction or reconsolidation to occur. Extinction and reconsolidation can both lead to changes in the expression of threat-induced defense responses, but differ in stability and have a different neural basis. This review presents the behavioral models and the system-level neural mechanisms in animals and humans of threat learning and modulation. PMID- 26267314 TI - The blood-cerebrospinal fluid barrier--first evidence for an active transport of organic mercury compounds out of the brain. AB - Exposure to organic mercury compounds promotes primarily neurological effects. Although methylmercury is recognized as a potent neurotoxicant, its transfer into the central nervous system (CNS) is not fully evaluated. While methylmercury and thiomersal pass the blood-brain barrier, limited data are available regarding the second brain regulating interface, the blood-cerebrospinal fluid (CSF) barrier. This novel study was designed to investigate the effects of organic as well as inorganic mercury compounds on, and their transfer across, a porcine in vitro model of the blood-CSF barrier for the first time. The barrier system is significantly more sensitive towards organic Hg compounds as compared to inorganic compounds regarding the endpoints cytotoxicity and barrier integrity. Whereas there are low transfer rates from the blood side to the CSF side, our results strongly indicate an active transfer of the organic mercury compounds out of the CSF. These results are the first to demonstrate an efflux of organic mercury compounds regarding the CNS and provide a completely new approach in the understanding of mercury compounds specific transport. PMID- 26267315 TI - A high precision apparatus for intracellular thermal response at single-cell level. AB - In this work, a nanoprobe that is highly thermo-sensitive to tiny temperature changes was prepared based on a thermocouple metal junction. A series of electro element apparatuses were integrated to accomplish single-cell temperature measurement. The temperature measurement probe (TMP) was constructed by tungsten (W), polyurethane (PU), and platinum (Pt). The tip size of TMP was characterized at less than 500 nm, and the tip angle was between 10 and 20 degrees with the resistance in the range of 500 to 1500 Omega. The single-cell temperature measurement probes were calibrated and calculated with a Seebeck coefficient ranging from 6 to 8 MUV degrees C(-1) at a precision of 0.1 degrees C. Monitoring the temperature at a single-cell level by inserting the TMP in marine lung epithelia (MLE)-12 cells displayed that the stimulation of lipopolysaccharide (LPS) and cobalt chloride induced different single-cell temperature fluctuation. This investigation could help reveal complex cellular functions and develop novel diagnoses. PMID- 26267316 TI - Mechanisms of Enhanced Electrocatalytic Activity for Oxygen Reduction Reaction on High-Index Platinum n(111)-(111) Surfaces. AB - Oxygen reduction reactions (ORRs) on high-index planes of Pt n(111)-(111) were studied by density functional theory (DFT). The stepped surfaces, where n = 2, 3, and 4, showed that O2, O, and OH exhibited higher binding energies along the step compared to the terrace plane. The Pt atoms along the step can become distorted through the binding of the O and OH, where the shift in position of the Pt atoms is the largest along the stepped sites, hence forming stronger bonds with O atoms. One of the two O atoms produced from the bond dissociation of O2 will push the other one down a step with lower binding energies, consequently reducing the energy required for the protonation reaction (O + H(+) -> OH, and OH + H(+) -> H2O). The quicker recovery back to the clean Pt surface would therefore improve the catalytic properties of Pt nanoparticles, especially those with exposure to high-indexed facets. PMID- 26267317 TI - The role of interleukin-8 (IL-8) and IL-8 receptors in platinum response in high grade serous ovarian carcinoma. AB - Platinum based drugs are the cornerstone of chemotherapy for ovarian cancer, however the development of chemoresistance hinders its success. IL-8 is involved in regulating several pro-survival pathways in cancer. We studied the expression of IL-8 and IL-8 receptors in platinum sensitive and resistant cell lines. Using qRT-PCR and immunohistochemistry, both platinum sensitive (PEA1, PEO14) and resistant (PEA2, PEO23) show increased expression of IL-8 and IL-8 receptors. IL 8RA shows nuclear and cytoplasmic expression, whilst IL-8RB is present solely in the cytoplasm. Knockdown of IL-8 increased sensitivity to cisplatin in platinum sensitive and reversed platinum resistance in resistant cell lines, decreased the expression of anti-apoptotic Bcl-2 and decreased inhibitory phosphorylation of pro-apoptotic Bad. IL-8 receptor antagonist treatment also enhanced platinum sensitivity. Nuclear localisation of IL-8RA was only detected in platinum resistant tumours. Inhibition of IL-8 signalling can enhance response in platinum sensitive and resistant disease. Nuclear IL-8RA may have potential as a biomarker of resistant disease. PMID- 26267318 TI - DNA repair prognostic index modelling reveals an essential role for base excision repair in influencing clinical outcomes in ER negative and triple negative breast cancers. AB - Stratification of oestrogen receptor (ER) negative and triple negative breast cancers (TNBCs) is urgently needed. In the current study, a cohort of 880 ER- (including 635 TNBCs) was immuno-profiled for a panel of DNA repair proteins including: Pol beta, FEN1, APE1, XRCC1, SMUG1, PARP1, BRCA1, ATR, ATM, DNA-PKcs, Chk1, Chk2, p53, and TOPO2. Multivariate Cox proportional hazards models (with backward stepwise exclusion of these factors, using a criterion of p < 0.05 for retention of factors in the model) were used to identify factors that were independently associated with clinical outcomes. XRCC1 (p = 0.002), pol beta (p = 0.032) FEN1 (p = 0.001) and BRCA1 (p = 0.040) levels were independently associated with poor BCSS. Subsequently, DNA repair index prognostic (DRPI) scores for breast cancer specific survival (BCSS) were calculated and two prognostic groups (DRPI-PGs) were identified. Patients in prognostic group 2 (DRPI-PG2) have higher risk of death (p < 0.001). Furthermore, in DRPI-PG2 patients, exposure to anthracycline reduced the risk of death [(HR (95% CI) = 0.79 (0.64-0.98), p = 0.032) by 21-26%. In addition, DRPI-PG2 patients have adverse clinicopathological features including higher grade, lympho-vascular invasion, Her-2 positive phenotype, compared to those in DRPI-PG1 (p < 0.01). Receiver operating characteristic (ROC) curves indicated that the DRPI outperformed the currently used prognostic factors and adding DRPI to lymph node stage significantly improved their performance as a predictor for BCSS [p < 0.00001, area under curve (AUC) = 0.70]. BER strongly influences pathogenesis of ER- and TNBCs. The DRPI accurately predicts BCSS and can also serve as a valuable prognostic and predictive tool for TNBCs. PMID- 26267319 TI - RTVP-1 promotes mesenchymal transformation of glioma via a STAT-3/IL-6-dependent positive feedback loop. AB - Glioblastomas (GBMs), the most aggressive primary brain tumors, exhibit increased invasiveness and resistance to anti-tumor treatments. We explored the role of RTVP-1, a glioma-associated protein that promotes glioma cell migration, in the mesenchymal transformation of GBM. Analysis of The Cancer Genome Atlas (TCGA) demonstrated that RTVP-1 expression was higher in mesenchymal GBM and predicted tumor recurrence and poor clinical outcome. ChiP analysis revealed that the RTVP 1 promoter binds STAT3 and C/EBPbeta, two master transcription factors that regulate mesenchymal transformation of GBM. In addition, IL-6 induced RTVP-1 expression in a STAT3-dependent manner. RTVP-1 increased the migration and mesenchymal transformation of glioma cells. Similarly, overexpression of RTVP-1 in human neural stem cells induced mesenchymal differentiation, whereas silencing of RTVP-1 in glioma stem cells (GSCs) decreased the mesenchymal transformation and stemness of these cells. Silencing of RTVP-1 also increased the survival of mice bearing GSC-derived xenografts. Using gene array analysis of RTVP-1 silenced glioma cells we identified IL-6 as a mediator of RTVP-1 effects on the mesenchymal transformation and migration of GSCs, therefore acting in a positive feedback loop by upregulating RTVP-1 expression via the STAT3 pathway. Collectively, these results implicate RTVP-1 as a novel prognostic marker and therapeutic target in GBM. PMID- 26267320 TI - Development and exploitation of a novel mutant androgen receptor modelling strategy to identify new targets for advanced prostate cancer therapy. AB - The persistence of androgen receptor (AR) signalling in castrate-resistant prostate cancer (CRPC) highlights the unmet clinical need for the development of more effective AR targeting therapies. A key mechanism of therapy-resistance is by selection of AR mutations that convert anti-androgens to agonists enabling the retention of androgenic signalling in CRPC. To improve our understanding of these receptors in advanced disease we developed a physiologically-relevant model to analyse the global functionality of AR mutants in CRPC. Using the bicalutamide activated AR(W741L/C) mutation as proof of concept, we demonstrate that this mutant confers an androgenic-like signalling programme and growth promoting phenotype in the presence of bicalutamide. Transcriptomic profiling of AR(W741L) highlighted key genes markedly up-regulated by the mutant receptor, including TIPARP, RASD1 and SGK1. Importantly, SGK1 expression was found to be highly expressed in the KUCaP xenograft model and a CRPC patient biopsy sample both of which express the bicalutamide-activated receptor mutant. Using an SGK1 inhibitor, AR(W741L) transcriptional and growth promoting activity was reduced indicating that exploiting functional distinctions between receptor isoforms in our model may provide new and effective therapies for CRPC patients. PMID- 26267321 TI - The PI3K/AKT/mTOR pathway is a potential predictor of distinct invasive and migratory capacities in human ovarian cancer cell lines. AB - OBJECTIVES: To explore the genetic and molecular events that control subclones exhibiting distinct invasive/migratory capacities derived from human epithelial ovarian cancer (EOC) cell line A2780 and SKOV3. METHODS: Single-cell subclones were isolated and established that were derived from the SKOV3 and A2780 cell lines through limiting dilution methodology. Transwell insert assays and MTT assays were performed to screen and identify the subclones exhibiting the highest and the lowest invasive/migratory capacities, and the selected subclones were renamed as A-H (A2780 high), A-L (A2780 low), S-H (SKOV3 high), and S-L (SKOV3 low). Their biological characteristics were evaluated. RNA-Seq was conducted on the targeted subclones. RESULTS: Compared with their corresponding counterparts, A-H/S-H cells exhibited significantly higher invasive/migratory capacities (P < 0.001 and = 0.001, respectively). A-H/S-H cells displayed a clear reduction in doubling time (P = 0.004 and 0.001, respectively), and a significant increase in the percentage of cells in S phase (P = 0.004 and 0.022, respectively). Additionally, the apoptotic rates of A-H/S-H cells were significantly lower than those of A-L/S-L cells (P = 0.002 and 0.026, respectively). At both mRNA and protein levels, caspase-3 and caspase-7 expression were reduced but Bcl-2 expression was increased in A-H/S-H cells. The TrkB (anoikis-related) and Beclin1 (autophagy-related) levels were consistently high and low, respectively, in both A-H/S-H cells. Resistance to chemotherapy in vitro and higher capacities on tumor formation in vivo was presented in both A-H/S-H cells. PI3K/AKT/mTOR pathway components, PIK3CA, PIK3CD, AKT3, ECM1, GPCR, mTOR and PRKCB were increased but that the Nur77 and PTEN were decreased in A-H/S-H cells, identified by RNA-Seq and consistently confirmed by RT-PCR and Western blot analyses. CONCLUSIONS: Heterogeneous cell subpopulations exhibiting distinct invasive and migratory capacities co-exist within the SKOV3 and A2780 cell lines. PI3K/AKT/mTOR pathway activation is associated with higher invasive and migratory capacities in subpopulations of human ovarian cancer cell lines. Inhibiting this pathway may be useful for the chemoprevention or treatment of EOC. PMID- 26267322 TI - IKK inhibition increases bortezomib effectiveness in ovarian cancer. AB - Ovarian cancer is associated with increased expression of the pro-angiogenic chemokine interleukin-8 (IL-8, CXCL8), which induces tumor cell proliferation, angiogenesis, and metastasis. Even though bortezomib (BZ) has shown remarkable anti-tumor activity in hematological malignancies, it has been less effective in ovarian cancer; however, the mechanisms are not understood. We have recently shown that BZ unexpectedly induces the expression of IL-8 in ovarian cancer cells in vitro, by IkappaB kinase (IKK)-dependent mechanism. Here, we tested the hypothesis that IKK inhibition reduces the IL-8 production and increases BZ effectiveness in reducing ovarian tumor growth in vivo. Our results demonstrate that the combination of BZ and the IKK inhibitor Bay 117085 significantly reduces the growth of ovarian tumor xenografts in nude mice when compared to either drug alone. Mice treated with the BZ/Bay 117085 combination exhibit smallest tumors, and lowest levels of IL-8. Furthermore, the reduced tumor growth in the combination group is associated with decreased tumor levels of S536P-p65 NFkappaB and its decreased recruitment to IL-8 promoter in tumor tissues. These data provide the first in vivo evidence that combining BZ with IKK inhibitor is effective, and suggest that using IKK inhibitors may increase BZ effectiveness in ovarian cancer treatment. PMID- 26267323 TI - Enhanced detection and comprehensive in situ phenotypic characterization of circulating and disseminated heteroploid epithelial and glioma tumor cells. AB - Conventional strategy of anti-EpCAM capture and immunostaining of cytokeratins (CKs) to detect circulating tumor cells (CTCs) is limited by highly heterogeneous and dynamic expression or absence of EpCAM and/or CKs in CTCs. In this study, a novel integrated cellular and molecular approach of subtraction enrichment (SE) and immunostaining-FISH (iFISH) was successfully developed. Both large or small size CTCs and circulating tumor microemboli (CTM) in various biofluid samples including cerebrospinal fluid (CSF) of cancer patients and patient-derived xenograft (PDX) mouse models were efficiently enriched and comprehensively identified and characterized by SE-iFISH. Non-hematopoietic CTCs with heteroploid chromosome 8 were detected in 87-92% of lung, esophageal and gastric cancer patients. Characterization of CTCs performed by CK18-iFISH showed that CK18, the dual epithelial marker and tumor biomarker, was strong positive in only 14% of lung and 24% of esophageal CTCs, respectively. Unlike conventional methodologies restricted only to the large and/or both EpCAM and CK positive CTCs, SE-iFISH enables efficient enrichment and performing in situ phenotypic and karyotypic identification and characterization of the highly heterogeneous CTC subtypes classified by both chromosome ploidy and the expression of various tumor biomarkers. Each CTC subtype may possess distinct clinical significance relative to tumor metastasis, relapse, therapeutic drug sensitivity or resistance, etc. PMID- 26267325 TI - A sulfonated polyaniline with high density and high rate Na-storage performances as a flexible organic cathode for sodium ion batteries. AB - A Na-rich cathode is developed by grafting the electron-withdrawing -SO3Na group on polyaniline chains. Due to the immobile doping and effective activation of the sulfonate group, this polymer demonstrates a high capacity (133 mA h g(-1)) and excellent cyclability through a cation-exchange reaction, offering a low cost and sustainable cathode for SIBs. PMID- 26267327 TI - Genetics of Apparently Sporadic Pheochromocytoma and Paraganglioma in a Chinese Population. AB - Identification of germline mutation in patients with apparently sporadic pheochromocytomas and paragangliomas is crucial. Clinical indicators, which include young age, bilateral or multifocal, extra-adrenal, malignant, or recurrent tumors, predict the likelihood of harboring germline mutation in Caucasian subjects. However, data on the prevalence of germline mutation, as well as the applicability of these clinical indicators in Chinese, are lacking. We conducted a cross-sectional study at a single endocrine tertiary referral center in Hong Kong. Subjects with pheochromocytomas and paragangliomas were evaluated for the presence of germline mutations involving 10 susceptibility genes, which included NF1, RET, VHL, SDHA, SDHB, SDHC, SDHD, TMEM 127, MAX, and FH genes. Clinical indicators were assessed for their association with the presence of germline mutations. Germline mutations, 2 being novel, were found in 24.4% of the 41 Chinese subjects recruited and 11.4% among those with apparently sporadic presentation. The increasing number of the afore-mentioned clinical indicators significantly correlated with the likelihood of harboring germline mutation in one of the 10 susceptibility genes. (r=0.757, p=0.026). The presence of 2 or more clinical indicators should prompt genetic testing for germline mutations in Chinese subjects. In conclusion, our study confirmed that a significant proportion of Chinese subjects with apparently sporadic pheochromocytoma and paraganglioma harbored germline mutations and these clinical indicators identified from Caucasians series were also applicable in Chinese subjects. This information will be of clinical relevance in the design of appropriate genetic screening strategies in Chinese populations. PMID- 26267326 TI - Metallothionein differentially affects the host response to Listeria infection both with and without an additional stress from cold-restraint. AB - Acute stress alters anti-bacterial defenses, but the neuroimmunological mechanisms underlying this association are not yet well understood. Metallothionein (MT), a cysteine-rich protein, is a stress response protein that is induced by a variety of chemical, biological, and psychological stressors, and MT has been shown to influence immune activities. We investigated MT's role in the management of anti-bacterial responses that occur during stress, using a C57BL/6 (B6) strain that has targeted disruptions of the Mt1 and Mt2 genes (B6 MTKO), and a B6 strain that has additional copies of Mt (B6-MTTGN). The well characterized listeriosis model was used to examine immune mechanisms that are altered by a 1-h stress treatment (cold-restraint, CR) administered just prior to bacterial infection. Intriguingly, MT gene doses both greater and lower than that of wild-type (WT) B6 mice were associated with improved host defenses against Listeria monocytogenes (LM). This augmented protection was diminished by CR stress in the MTKO mice, but transgenic mice with additional MT copies had no CR stress-induced increase in their listerial burden. During the transition from innate to adaptive immunity, on day 3 after infection, oxidative burst and apoptosis were assessed by flow cytometric methods, and cytokine transcription was measured by real-time quantitative PCR. MT gene expression and CR-stress affected the expression of IL-6 and TNFalpha. Additionally, these genetic and environmental modulations altered the generation of ROS responses as well as the number of apoptotic cells in livers and spleens. Although the level of MT altered the listerial response, MT expression was equally elevated by listerial infection with or without CR stress. These results indicate the ability of MT to regulate immune response mechanisms and demonstrate that increased amounts of MT can eliminate the immunosuppression induced by CR. PMID- 26267328 TI - Selenium Supplementation and the Effects on Reproductive Outcomes, Biomarkers of Inflammation, and Oxidative Stress in Women with Polycystic Ovary Syndrome. AB - Selenium supplementation could be effective on reproductive outcomes, biomarkers of inflammation, and oxidative stress among women with polycystic ovary syndrome (PCOS). The aim of the study was to determine the effects of selenium supplementation on reproductive outcomes, biomarkers of inflammation, and oxidative stress in PCOS patients. The present randomized double-blind, placebo controlled trial was conducted on 64 women aged 18-40 years old with PCOS at the clinic affiliated to Ardabil University of Medical Sciences, Ardabil, Iran. The participants were randomly assigned to 2 groups receiving either 200 MUg selenium daily (n=32) or placebo (n=32) for 8 weeks. Hormonal profiles, biomarkers of inflammation, and oxidative stress were measured and compared both before and after the treatment. After 8 weeks of intervention, pregnancy rate in the selenium group was higher than in the placebo group: 18.8 (6/32) vs. 3.1% (1/32), p=0.04. In addition, alopecia (40.6 vs. 9.4%, p=0.004) and acne (46.9 vs. 12.5 %, p=0.003) decreased following the consumption of selenium supplements compared with placebo. Additionally, patients who received selenium supplements had significantly decreased serum dehydroepiandrosterone (DHEA) levels (p=0.02), hirsutism (modified Ferriman-Gallwey scores) (p<0.001), serum high sensitivity C reactive protein (hs-CRP) (p=0.02), and plasma malondialdehyde (MDA) levels (p=0.01) compared with placebo. We did not observe any significant effects of taking selenium supplements on other hormonal profiles, nitric oxide (NO), and other biomarkers of oxidative stress. Taken together, selenium supplementation for 8 weeks among PCOS women had beneficial effects on reproductive outcomes, DHEA, hs-CRP, and MDA levels. Supporting Information for this article is available online at http://www.thieme-connect.de/products. PMID- 26267324 TI - Molecular classification of gastric cancer: Towards a pathway-driven targeted therapy. AB - Gastric cancer (GC) is the third leading cause of cancer mortality worldwide. Although surgical resection is a potentially curative approach for localized cases of GC, most cases of GC are diagnosed in an advanced, non-curable stage and the response to traditional chemotherapy is limited. Fortunately, recent advances in our understanding of the molecular mechanisms that mediate GC hold great promise for the development of more effective treatment strategies. In this review, an overview of the morphological classification, current treatment approaches, and molecular alterations that have been characterized for GC are provided. In particular, the most recent molecular classification of GC and alterations identified in relevant signaling pathways, including ErbB, VEGF, PI3K/AKT/mTOR, and HGF/ MET signaling pathways, are described, as well as inhibitors of these pathways. An overview of the completed and active clinical trials related to these signaling pathways are also summarized. Finally, insights regarding emerging stem cell pathways are described, and may provide additional novel markers for the development of therapeutic agents against GC. The development of more effective agents and the identification of biomarkers that can be used for the diagnosis, prognosis, and individualized therapy for GC patients, have the potential to improve the efficacy, safety, and cost effectiveness for GC treatments. PMID- 26267329 TI - Reply: To PMID 26031848. PMID- 26267330 TI - Re-conceptualizing ASD Within a Dimensional Framework: Positive, Negative, and Cognitive Feature Clusters. AB - Introduction of the National Institute of Mental Health's Research Domain Criteria and revision of diagnostic classification for Autism Spectrum Disorder in the latest diagnostic manual call for a new way of conceptualizing heterogeneous ASD features. We propose a novel conceptualization of ASD, borrowing from the schizophrenia literature in clustering ASD features along positive, negative, and cognitive dimensions. We argue that this dimensional conceptualization can offer improved ability to classify, diagnose, and treat, to apply and predict response to treatment, and to explore underlying neural and genetic alterations that may contribute to particular feature clusters. We suggest the proposed conceptualization can advance the field in a manner that may prove clinically and biologically useful for understanding and addressing heterogeneity within ASD. PMID- 26267331 TI - Collective intelligence meets medical decision-making: the collective outperforms the best radiologist. AB - While collective intelligence (CI) is a powerful approach to increase decision accuracy, few attempts have been made to unlock its potential in medical decision making. Here we investigated the performance of three well-known collective intelligence rules ("majority", "quorum", and "weighted quorum") when applied to mammography screening. For any particular mammogram, these rules aggregate the independent assessments of multiple radiologists into a single decision (recall the patient for additional workup or not). We found that, compared to single radiologists, any of these CI-rules both increases true positives (i.e., recalls of patients with cancer) and decreases false positives (i.e., recalls of patients without cancer), thereby overcoming one of the fundamental limitations to decision accuracy that individual radiologists face. Importantly, we find that all CI-rules systematically outperform even the best-performing individual radiologist in the respective group. Our findings demonstrate that CI can be employed to improve mammography screening; similarly, CI may have the potential to improve medical decision-making in a much wider range of contexts, including many areas of diagnostic imaging and, more generally, diagnostic decisions that are based on the subjective interpretation of evidence. PMID- 26267332 TI - A 2009 cross-sectional survey of procedures for post-mortem management of highly infectious disease patients in 48 isolation facilities in 16 countries: data from EuroNHID. AB - PURPOSE: The handling of human remains may pose a risk for transmission of highly infectious agents. The use of appropriate biosafety measures is very important in case of management of patients deceased from highly infectious diseases (HIDs), such as Ebola virus disease. This paper presents the capabilities and resources in this field in 16 European countries, and suggests indications for the safe post-mortem management of HID patients. METHODS: The European Network for Highly Infectious Diseases conducted in 2009 a survey in 48 isolation facilities in 16 European countries. A set of standardized checklists, filled during on-site visits, have been used for data collection. RESULTS: Thirty-nine facilities (81.2%) reported to have written procedures for the management of human remains, and 27 (56.2%) for the performance of autopsies in HID patients. A Biosafety Level 3 autopsy room was available in eight (16.6%) facilities, other technical devices for safe autopsies were available in nine (18.7%). Overall, four facilities (8.3%) reported to have all features explored for the safe management of human remains. Conversely, in five (10.4%) none of these features were available. CONCLUSIONS: The level of preparedness of surveyed isolation facilities in the field of post-mortem management in case of HIDs was not satisfactory, and improvements are needed. PMID- 26267333 TI - Optical spectroscopic determination of human meniscus composition. AB - This study investigates the correlation between the composition of human meniscus and its absorption spectrum in the visible (VIS) and near infrared (NIR) spectral range. Meniscus samples (n = 24) were obtained from nonarthritic knees of human cadavers with no history of joint diseases. Specimens (n = 72) were obtained from three distinct sections of the meniscus, namely; anterior, center, posterior. Absorption spectra were acquired from each specimen in the VIS and NIR spectral range (400-1,100 nm). Following spectroscopic probing, the specimens were subjected to biochemical analyses to determine the matrix composition, that is water, hydroxyproline, and uronic acid contents. Multivariate analytical techniques, including principal component analysis (PCA) and partial least squares (PLS) regression, were then used to investigate the correlation between the matrix composition and it spectral response. Our results indicate that the optical absorption of meniscus matrix is related to its composition, and this relationship is optimal in the NIR spectral range (750-1,100 nm). High correlations (R(2) (uronic) = 86.9%, R(2) (water) = 83.8%, R(2) (hydroxyproline) = 81.7%, p < 0.0001) were obtained between the spectral predicted and measured meniscus composition, thus suggesting that spectral data in the NIR range can be utilized for estimating the matrix composition of human meniscus. In conclusion, optical spectroscopy, particularly in the NIR spectral range, is a potential method for evaluating the composition of human meniscus. This presents a promising technique for rapid and nondestructive evaluation of meniscus integrity in real-time during arthroscopic surgery. PMID- 26267334 TI - Lung Cancer Onset in Wild Type Mice Following Bone Marrow Reconstitution with kras(v12) Cells. AB - A role for bone-marrow-derived cells (BMDCs) in tissue repair and malignancy onset has been proposed, but their contribution is still debated. We tested the ability of BMDCs containing the inducible kras(V12) oncogene to initiate lung adenocarcinoma. For our experimental strategy, we reconstituted lethally irradiated wild type mice with BMDCs carrying inducible kras(V12) and subsequently induced oncogene expression by 4-OHT administration. Epithelial lung lesions, from adenoma to adenocarcinomas, appeared at successive time points. These results show that lung tumors were derived from donor BMDCs and indicate a direct involvement of bone marrow cells in the development of epithelial cancers. PMID- 26267335 TI - Sinobacterium norvegicum sp. nov., isolated from great scallop (Pecten maximus) broodstock and emended description of Sinobacterium caligoides. AB - Six isolates were recovered from great scallop (Pecten maximus) broodstock in a hatchery in Bergen, Norway. The strains were thoroughly characterized by a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences indicated that these strains are related to the genus Sinobacterium, showing sequence similarities between 96.97 and 97.63 % with the only species of the genus, Sinobacterium caligoides. Phenotypic characterization showed that the strains are typical marine halophiles, Gram negative, aerobic chemoorganotrophs, and allowed their differentiation from the closely related taxa. The G+C content of the novel strains was 52.2 +/- 1 mol% and the predominant fatty acids were C16:0, C16:1 omega7c/C16:1 omega6c and C18:1 omega7c. The value for DNA-DNA relatedness between strain 3CM4(T) and the S. caligoides type strain LMG 25705(T) was 46 %. Hybridization values between strain 3CM4(T) and the other scallop isolates ranged from 82 to 93.6 %. Based on all data collected, the six scallop strains represent a novel species of the genus Sinobacterium, for which the name Sinobacterium norvegicum sp. nov., is proposed with strain 3CM4(T) (=CECT 8267(T); =CAIM 1884(T)) as type strain. PMID- 26267336 TI - Sup35 methionine oxidation is a trigger for de novo [PSI(+)] prion formation. AB - The molecular basis by which fungal and mammalian prions arise spontaneously is poorly understood. A number of different environmental stress conditions are known to increase the frequency of yeast [PSI(+)] prion formation in agreement with the idea that conditions which cause protein misfolding may promote the conversion of normally soluble proteins to their amyloid forms. A recent study from our laboratory has shown that the de novo formation of the [PSI(+)] prion is significantly increased in yeast mutants lacking key antioxidants suggesting that endogenous reactive oxygen species are sufficient to promote prion formation. Our findings strongly implicate oxidative damage of Sup35 as an important trigger for the formation of the heritable [PSI(+)] prion in yeast. This review discusses the mechanisms by which the direct oxidation of Sup35 might lead to structural transitions favoring conversion to the transmissible amyloid-like form. This is analogous to various environmental factors which have been proposed to trigger misfolding of the mammalian prion protein (PrP(C)) into the aggregated scrapie form (PrP(Sc)). PMID- 26267337 TI - Comparative Study for Efficacy and Safety of Adenoidectomy according to the Surgical Method: A Prospective Multicenter Study. AB - BACKGROUND/OBJECTIVE: There have been several operative techniques for adenoidectomy and their efficacy and morbidity are different according to the technique. This prospective multicenter study was aimed to compare the efficacy and morbidity of coblation adenoidectomy (CA) with those of power-assisted adenoidectomy. STUDY DESIGN: Prospective multi-institutional study. METHODS: Children who underwent CA, power-assisted adenoidectomy with cauterization (PAA+C) or without cauterization (PAA-C) due to adenoid hypertrophy were enrolled from 13 hospitals between July 2013 and June 2014. Mean operation time, degree of intraoperative bleeding and postoperative bleeding rate were evaluated. RESULTS: A total of 388 children (mean age +/- standard deviation = 6.6 +/- 2.5 years; 245 males and 143 females) were included. According to the adenoidectomy technique, the children were classified into 3 groups: (1) CA (n = 116); (2) PAA+C (n = 153); and (3) PAA-C (n = 119). Significant differences were not found in age and sex among three groups. In the CA group, mean operation time was significantly shorter (P < 0.001) and degree of intraoperative bleeding was significantly less (P < 0.001) compared to PAA+C or PAA-C group. Delayed postoperative bleeding rate of PAA-C group was significantly higher than that of CA or PAA+C group (P = 0.016). CONCLUSIONS: This prospective multicenter study showed that CA was superior to PAA in terms of mean operation time and degree of intraoperative bleeding. PMID- 26267338 TI - Soil Microbial Community Structure and Metabolic Activity of Pinus elliottii Plantations across Different Stand Ages in a Subtropical Area. AB - Soil microbes play an essential role in the forest ecosystem as an active component. This study examined the hypothesis that soil microbial community structure and metabolic activity would vary with the increasing stand ages in long-term pure plantations of Pinus elliottii. The phospholipid fatty acids (PLFA) combined with community level physiological profiles (CLPP) method was used to assess these characteristics in the rhizospheric soils of P. elliottii. We found that the soil microbial communities were significantly different among different stand ages of P. elliottii plantations. The PLFA analysis indicated that the bacterial biomass was higher than the actinomycic and fungal biomass in all stand ages. However, the bacterial biomass decreased with the increasing stand ages, while the fungal biomass increased. The four maximum biomarker concentrations in rhizospheric soils of P. elliottii for all stand ages were 18:1omega9c, 16:1omega7c, 18:3omega6c (6,9,12) and cy19:0, representing measures of fungal and gram negative bacterial biomass. In addition, CLPP analysis revealed that the utilization rate of amino acids, polymers, phenolic acids, and carbohydrates of soil microbial community gradually decreased with increasing stand ages, though this pattern was not observed for carboxylic acids and amines. Microbial community diversity, as determined by the Simpson index, Shannon-Wiener index, Richness index and McIntosh index, significantly decreased as stand age increased. Overall, both the PLFA and CLPP illustrated that the long-term pure plantation pattern exacerbated the microecological imbalance previously described in the rhizospheric soils of P. elliottii, and markedly decreased the soil microbial community diversity and metabolic activity. Based on the correlation analysis, we concluded that the soil nutrient and C/N ratio most significantly contributed to the variation of soil microbial community structure and metabolic activity in different stand ages of P. elliottii plantations. PMID- 26267339 TI - Muscle activation, blood lactate, and perceived exertion responses to changing resistance training programming variables. AB - Ratings of perceived exertion (RPE: 0-10) during resistance training with varying programming demands were examined. Blood lactate (BLa) and muscle activation (using surface electromyography: EMG) were measured as potential mediators of RPE responses. Participants performed three sets of single arm (preferred side) bicep curls at 70% of 1 repetition maximum over 4 trials: Trial (A) 3 sets * 8 repetitions * 120 s recovery between sets; (B) 3 sets * 8 repetitions * 240 s recovery; (C) 3 sets * maximum number of repetitions (MNR) * 120 s recovery; (D) 3 sets * MNR * 240 s recovery. Overall body (RPE-O) and active muscle (RPE-AM) perceptual responses were assessed following each set in each trial. Biceps brachii and brachioradialis muscle EMG was measured during each set for each trial. RPE-O and RPE-AM were not different between Trial A (3.5 +/- 1 and 6 +/- 1, respectively) and Trial B (3.5 +/- 1 and 5.5 +/- 1, respectively) (p < .05). However, RPE-AM was significantly greater in Trial C (7.5 +/- 1.5) and Trial D (7.5 +/- 1.5) than in Trial B (p < .05). There were no significant differences in muscle activation or BLa between trials; however, work rate (tonnage/min) was greater in Trials C and D compared to Trial B. In conclusion, BLa and muscle activation were not related to RPE, but resistance training variables, such as work rate, may impact on RPE when intensity (%1RM) and the number of sets completed remain constant. PMID- 26267340 TI - Of orange and yellow eyelids. PMID- 26267341 TI - Robust Gene-Gene Interaction Analysis in Genome Wide Association Studies. AB - Genome-wide association studies (GWAS) have successfully discovered hundreds of associations between genetic variants and complex traits. Most GWAS have focused on the identification of single variants. It has been shown that most of the variants that were discovered by GWAS could only partially explain disease heritability. The explanation for this missing heritability is generally believed to be gene-gene (GG) or gene-environment (GE) interactions and other structural variants. Generalized multifactor dimensionality reduction (GMDR) has been proven to be reasonably powerful in detecting GG and GE interactions; however, its performance has been found to decline when outlying quantitative traits are present. This paper proposes a robust GMDR estimation method (based on the L estimator and M-estimator estimation methods) in an attempt to reduce the effects caused by outlying traits. A comparison of robust GMDR with the original MDR based on simulation studies showed the former method to outperform the latter. The performance of robust GMDR is illustrated through a real GWA example consisting of 8,577 samples from the Korean population using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) level as a phenotype. Robust GMDR identified the KCNH1 gene to have strong interaction effects with other genes on the function of insulin secretion. PMID- 26267348 TI - Adverse childhood experiences, depression and mental health barriers to work among low-income women. AB - Recent research has connected childhood abuse to decreased physical and mental health for low-income women in Utah. Further, mental health has established a link to employment problems. This study conducted a secondary analysis of data collected from individuals accessing public assistance to investigate the relationships among retrospective self-reports of childhood emotional, physical and sexual abuse and prospective indicators of mental health and mental health barriers to work. Logistic regression models found strong relationships between childhood abuse and increased odds of depression and mental health barriers to work. Path models highlight the relative importance of depression for those reporting mental health as the biggest barrier to work. Recommendations for social workers, public health professionals, and program administrators are provided. PMID- 26267349 TI - In Vitro Biocompatibility of Surface-Modified Porous Alumina Particles for HepG2 Tumor Cells: Toward Early Diagnosis and Targeted Treatment. AB - Porous alumina photoluminescence-inherent particles are produced and proposed for the development of biomarkers detectors and localized treatment of HepG2 cells. Nanoporous alumina particles (NPAPs) are amorphous, consist of hexagonally ordered nanometric pores in an alumina matrix, have high chemical stability in physiological pH, and exhibit a high inherent photoluminescence in the visible spectrum independently of their size, selectable from nanometers to tens of micrometers. The surface of NPAPs is chemically modified using two different functionalization methods, a multistep method with (3-aminopropyl)triethoxysilane (APTES) and glutaraldehyde (GLTA) and a novel simplified-step method with silane PEG-NHS. Fourier Transform infrared spectroscopy analysis confirmed the proper surface modification of the particles for both functionalization methods. HepG2 cells were cultured during different times with growing concentrations of particles. The analysis of cytotoxicity and cell viability of HepG2 cells confirmed the good biocompatibility of NPAPs in all culture conditions. The results prove the suitability of NPAPs for developing new label-free biomarker detectors and advantageous carriers for localized drug delivery. PMID- 26267350 TI - Ferromagnetic Order, Strong Magnetocrystalline Anisotropy, and Magnetocaloric Effect in the Layered Telluride Fe(3-delta)GeTe2. AB - The ternary transition-metal compound Fe(3-delta)GeTe2 is formed for 0 < delta < 0.3. X-ray diffraction and Mossbauer spectroscopy reveal its layered crystal structure with occasional Fe vacancies in the Fe2 site, whereas no Fe atoms occupy the interlayer space, so that only van der Waals interactions exist between adjacent layers. We explore magnetic behavior and ensuing functional properties of Fe(2.9)GeTe2 via neutron diffraction, thermodynamic and transport measurements, Mossbauer spectroscopy, and electronic structure calculations. Below T(C) = 225 K, Fe(2.9)GeTe2 is ferromagnetically ordered with the magnetic moments of 1.95(5) and 1.56(4) MU(B) at T = 1.5 K, both directed along c, which is the magnetic easy axis. Electronic structure calculations confirm this magnetic structure and reveal a remarkably high easy-axis anisotropy of 4.2 meV/f.u. Mossbauer spectra reveal the magnetic ordering too, although a drastic influence of Fe vacancies on quadrupolar splittings and local magnetic fields has been observed. A moderate magnetocaloric effect with the magnetic entropy change upon the ferromagnetic ordering transition, -DeltaS ~ 1.1 J.kg(-1).K(-1) at 5 T, is found. PMID- 26267351 TI - Surgical Care of Pediatric Patients in the Humanitarian Setting: The Medecins Sans Frontieres Experience, 2012-2013. AB - IMPORTANCE: Little is known about the scope of practice and outcomes in pediatric surgery performed by humanitarian organizations in resource-poor settings and conflict zones. This study provides the largest report to date detailing such data for a major nongovernmental organization providing humanitarian surgical relief support in these settings. OBJECTIVE: To characterize pediatric surgical care provision by a major nongovernmental organization in specialized humanitarian settings and conflict zones. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted from August 15, 2014, to March 9, 2015, of 59,928 surgical interventions carried out from January 1, 2012, to December 31, 2013, by the Medecins Sans Frontieres Operational Centre Paris (MSF-OCP) program in 20 locations, including South Sudan, Yemen, Syria, Gaza, Pakistan, Nigeria, Central African Republic, Democratic Republic of Congo, and the Philippines. Surgical interventions were primarily for general surgical, traumatic, and obstetric emergencies and were categorized by mechanism, type of intervention, American Society of Anesthesia risk classification, and urgency of intervention. MAIN OUTCOMES AND MEASURES: Operative indications, type of intervention, and operative case mortality. RESULTS: Among all age groups, 59,928 surgical interventions were performed in dedicated trauma, obstetric, and reconstructive centers for 2 years. Nearly one-third of interventions (18,040 [30.1%]) involved preteen patients (aged <13 years) and 4571 (7.6%) involved teenaged patients (aged 13-17 years). The proportion of violence-related injuries in the preteen group was significantly lower than in the teenage group (4.8% vs 17.5%; P < .001). Burns (50.1%), other accidental injuries (16.4%), and infections (23.4%) composed the bulk of indications in the preteen group. Interventions in the teenage group were principally caused by trauma-related injuries (burns, 22.9%; traffic accidents, 10.1%; gunshot wounds, 8.0%). Crude perioperative case mortality rates were 0.07% in the preteen group, 0.15% in the teenage group, and 0.22% in the adult group (>17 years) (P = .001). One-third of the cases (33.4%) were deemed urgent, while most of the remaining cases (57.7%) were deemed semielective (surgical intervention to be performed within 48 hours). CONCLUSIONS AND RELEVANCE: When examining surgical interventions in a population of pediatric patients cared for in the specialized setting of humanitarian aid and conflict zones, burns, other accidental injuries, and infection composed the bulk of indications in the preteen group; interventions in the teenage group were principally caused by trauma-related injuries. Crude perioperative case mortality rates in the preteen group were significantly lower than in the adult group. Further work is needed to examine long-term outcomes of pediatric operations in these settings and to guide context-specific surgical program development. PMID- 26267352 TI - Artificial Photosynthesis on TiO2-Passivated InP Nanopillars. AB - Here, we report photocatalytic CO2 reduction with water to produce methanol using TiO2-passivated InP nanopillar photocathodes under 532 nm wavelength illumination. In addition to providing a stable photocatalytic surface, the TiO2 passivation layer provides substantial enhancement in the photoconversion efficiency through the introduction of O vacancies associated with the nonstoichiometric growth of TiO2 by atomic layer deposition. Plane wave-density functional theory (PW-DFT) calculations confirm the role of oxygen vacancies in the TiO2 surface, which serve as catalytically active sites in the CO2 reduction process. PW-DFT shows that CO2 binds stably to these oxygen vacancies and CO2 gains an electron (-0.897e) spontaneously from the TiO2 support. This calculation indicates that the O vacancies provide active sites for CO2 absorption, and no overpotential is required to form the CO2(-) intermediate. The TiO2 film increases the Faraday efficiency of methanol production by 5.7* to 4.79% under an applied potential of -0.6 V vs NHE, which is 1.3 V below the E(o)(CO2/CO2(-)) = 1.9 eV standard redox potential. Copper nanoparticles deposited on the TiO2 act as a cocatalyst and further improve the selectivity and yield of methanol production by up to 8-fold with a Faraday efficiency of 8.7%. PMID- 26267353 TI - Up-down hand position switch may delay the fatigue of non-dominant hand position rescuers and improve chest compression quality during cardiopulmonary resuscitation: a randomized crossover manikin study. AB - Previous studies have shown improved external chest compression (ECC) quality and delayed rescuer fatigue when the dominant hand (DH) was in contact with the sternum. However, many rescuers prefer placing the non-dominant hand (NH) in contact with the sternum during ECC. We aimed to investigate the effects of up down hand position switch on the quality of ECC and the fatigue of rescuers during cardiopulmonary resuscitation (CPR). After completion of a review of the standard adult basic life support (BLS) course, every candidate performed 10 cycles of single adult CPR twice on an adult manikin with either a constant hand position (CH) or a switched hand position (SH) in random order at 7-day intervals. The rescuers' general characteristics, hand positions, physiological signs, fatigue appearance and ECC qualities were recorded. Our results showed no significant differences in chest compression quality for the DH position rescuers between the CH and SH sessions (p>0.05, resp.). And also no significant differences were found for Borg score (p = 0.437) or cycle number (p = 0.127) of fatigue appearance after chest compressions between the two sessions. However, for NH position rescuers, the appearance of fatigue was delayed (p = 0.046), with a lower Borg score in the SH session (12.67 +/- 2.03) compared to the CH session (13.33 +/- 1.95) (p = 0.011). Moreover, the compression depth was significantly greater in the SH session (39.3 +/- 7.2 mm) compared to the CH session (36.3 +/- 8.1 mm) (p = 0.015). Our data suggest that the up-down hand position switch during CPR may delay the fatigue of non-dominant hand position rescuers and improve the quality of chest compressions. PMID- 26267354 TI - Behavioral and electrophysiological analysis of general anesthesia in 3 background strains of Drosophila melanogaster. AB - General anesthetics achieve behavioral unresponsiveness via a mechanism that is incompletely understood. The study of genetic model systems such as the fruit fly Drosophila melanogaster is crucial to advancing our understanding of how anesthetic drugs render animals unresponsive. Previous studies have shown that wild-type control strains differ significantly in their sensitivity to general anesthetics, which potentially introduces confounding factors for comparing genetic mutations placed on these wild-type backgrounds. Here, we examined a variety of behavioral and electrophysiological endpoints in Drosophila, in both adult and larval animals. We characterized these endpoints in 3 commonly used fly strains: wild-type Canton Special (CS), and 2 commonly used white-eyed strains, isoCJ1 and w(1118). We found that CS and isoCJ1 show remarkably similar sensitivity to isoflurane across a variety of behavioral and electrophysiological endpoints. In contrast, w(1118) is resistant to isoflurane compared to the other 2 strains at both the adult and larval stages. This resistance is however not reflected at the level of neurotransmitter release at the larval neuromuscular junction (NMJ). This suggests that the w(1118) strain harbors another mutation that produces isoflurane resistance, by acting on an arousal pathway that is most likely preserved between larval and adult brains. This mutation probably also affects sleep, as marked differences between isoCJ1 and w(1118) have also recently been found for behavioral responsiveness and sleep intensity measures. PMID- 26267355 TI - Synthesis and evaluation of chloramphenicol homodimers: molecular target, antimicrobial activity, and toxicity against human cells. AB - As fight against antibiotic resistance must be strengthened, improving old drugs that have fallen in reduced clinical use because of toxic side effects and/or frequently reported resistance, like chloramphenicol (CAM), is of special interest. Chloramphenicol (CAM), a prototypical wide-spectrum antibiotic has been shown to obstruct protein synthesis via binding to the bacterial ribosome. In this study we sought to identify features intensifying the bacteriostatic action of CAM. Accordingly, we synthesized a series of CAM-dimers with various linker lengths and functionalities and compared their efficiency in inhibiting peptide bond formation in an Escherichia coli cell-free system. Several CAM-dimers exhibited higher activity, when compared to CAM. The most potent of them, compound 5, containing two CAM bases conjugated via a dicarboxyl aromatic linker of six successive carbon-bonds, was found to simultaneously bind both the ribosomal catalytic center and the exit-tunnel, thus revealing a second, kinetically cryptic binding site for CAM. Compared to CAM, compound 5 exhibited comparable antibacterial activity against MRSA or wild-type strains of Staphylococcus aureus, Enterococcus faecium and E. coli, but intriguingly superior activity against some CAM-resistant E. coli and Pseudomonas aeruginosa strains. Furthermore, it was almost twice as active in inhibiting the growth of T leukemic cells, without affecting the viability of normal human lymphocytes. The observed effects were rationalized by footprinting tests, crosslinking analysis, and MD-simulations. PMID- 26267356 TI - Analysis of the Molecular Dialogue Between Gray Mold (Botrytis cinerea) and Grapevine (Vitis vinifera) Reveals a Clear Shift in Defense Mechanisms During Berry Ripening. AB - Mature grapevine berries at the harvesting stage (MB) are very susceptible to the gray mold fungus Botrytis cinerea, while veraison berries (VB) are not. We conducted simultaneous microscopic and transcriptomic analyses of the pathogen and the host to investigate the infection process developed by B. cinerea on MB versus VB, and the plant defense mechanisms deployed to stop the fungus spreading. On the pathogen side, our genome-wide transcriptomic data revealed that B. cinerea genes upregulated during infection of MB are enriched in functional categories related to necrotrophy, such as degradation of the plant cell wall, proteolysis, membrane transport, reactive oxygen species (ROS) generation, and detoxification. Quantitative-polymerase chain reaction on a set of representative genes related to virulence and microscopic observations further demonstrated that the infection is also initiated on VB but is stopped at the penetration stage. On the plant side, genome-wide transcriptomic analysis and metabolic data revealed a defense pathway switch during berry ripening. In response to B. cinerea inoculation, VB activated a burst of ROS, the salicylate dependent defense pathway, the synthesis of the resveratrol phytoalexin, and cell wall strengthening. On the contrary, in infected MB, the jasmonate-dependent pathway was activated, which did not stop the fungal necrotrophic process. PMID- 26267357 TI - Accuracy and reliability of 3D stereophotogrammetry: A comparison to direct anthropometry and 2D photogrammetry. AB - OBJECTIVE: To evaluate the accuracy of three-dimensional (3D) stereophotogrammetry by comparing it with the direct anthropometry and digital photogrammetry methods. The reliability of 3D stereophotogrammetry was also examined. MATERIALS AND METHODS: Six profile and four frontal parameters were directly measured on the faces of 80 participants. The same measurements were repeated using two-dimensional (2D) photogrammetry and 3D stereophotogrammetry (3dMDflex System, 3dMD, Atlanta, Ga) to obtain images of the subjects. Another observer made the same measurements for images obtained with 3D stereophotogrammetry, and interobserver reproducibility was evaluated for 3D images. Both observers remeasured the 3D images 1 month later, and intraobserver reproducibility was evaluated. Statistical analysis was conducted using the paired samples t-test, intraclass correlation coefficient, and Bland-Altman limits of agreement. RESULTS: The highest mean difference was 0.30 mm between direct measurement and photogrammetry, 0.21 mm between direct measurement and 3D stereophotogrammetry, and 0.5 mm between photogrammetry and 3D stereophotogrammetry. The lowest agreement value was 0.965 in the Sn-Pro parameter between the photogrammetry and 3D stereophotogrammetry methods. Agreement between the two observers varied from 0.90 (Ch-Ch) to 0.99 (Sn-Me) in linear measurements. For intraobserver agreement, the highest difference between means was 0.33 for observer 1 and 1.42 mm for observer 2. CONCLUSIONS: Measurements obtained using 3D stereophotogrammetry indicate that it may be an accurate and reliable imaging method for use in orthodontics. PMID- 26267358 TI - Tissue regeneration and biomineralization in sea urchins: role of Notch signaling and presence of stem cell markers. AB - Echinoderms represent a phylum with exceptional regenerative capabilities that can reconstruct both external appendages and internal organs. Mechanistic understanding of the cellular pathways involved in regeneration in these animals has been hampered by the limited genomic tools and limited ability to manipulate regenerative processes. We present a functional assay to investigate mechanisms of tissue regeneration and biomineralization by measuring the regrowth of amputated tube feet (sensory and motor appendages) and spines in the sea urchin, Lytechinus variegatus. The ability to manipulate regeneration was demonstrated by concentration-dependent inhibition of regrowth of spines and tube feet by treatment with the mitotic inhibitor, vincristine. Treatment with the gamma secretase inhibitor DAPT resulted in a concentration-dependent inhibition of regrowth, indicating that both tube feet and spine regeneration require functional Notch signaling. Stem cell markers (Piwi and Vasa) were expressed in tube feet and spine tissue, and Vasa-positive cells were localized throughout the epidermis of tube feet by immunohistochemistry, suggesting the existence of multipotent progenitor cells in these highly regenerative appendages. The presence of Vasa protein in other somatic tissues (e.g. esophagus, radial nerve, and a sub-population of coelomocytes) suggests that multipotent cells are present throughout adult sea urchins and may contribute to normal homeostasis in addition to regeneration. Mechanistic insight into the cellular pathways governing the tremendous regenerative capacity of echinoderms may reveal processes that can be modulated for regenerative therapies, shed light on the evolution of regeneration, and enable the ability to predict how these processes will respond to changing environmental conditions. PMID- 26267359 TI - Large-Scale Transcriptome Analysis in Faba Bean (Vicia faba L.) under Ascochyta fabae Infection. AB - Faba bean is an important food crop worldwide. However, progress in faba bean genomics lags far behind that of model systems due to limited availability of genetic and genomic information. Using the Illumina platform the faba bean transcriptome from leaves of two lines (29H and Vf136) subjected to Ascochyta fabae infection have been characterized. De novo transcriptome assembly provided a total of 39,185 different transcripts that were functionally annotated, and among these, 13,266 were assigned to gene ontology against Arabidopsis. Quality of the assembly was validated by RT-qPCR amplification of selected transcripts differentially expressed. Comparison of faba bean transcripts with those of better-characterized plant genomes such as Arabidopsis thaliana, Medicago truncatula and Cicer arietinum revealed a sequence similarity of 68.3%, 72.8% and 81.27%, respectively. Moreover, 39,060 single nucleotide polymorphism (SNP) and 3,669 InDels were identified for genotyping applications. Mapping of the sequence reads generated onto the assembled transcripts showed that 393 and 457 transcripts were overexpressed in the resistant (29H) and susceptible genotype (Vf136), respectively. Transcripts involved in plant-pathogen interactions such as leucine rich proteins (LRR) or plant growth regulators involved in plant adaptation to abiotic and biotic stresses were found to be differently expressed in the resistant line. The results reported here represent the most comprehensive transcript database developed so far in faba bean, providing valuable information that could be used to gain insight into the pathways involved in the resistance mechanism against A. fabae and to identify potential resistance genes to be further used in marker assisted selection. PMID- 26267361 TI - Ultra-wide bandwidth with enhanced microwave absorption of electroless Ni-P coated tetrapod-shaped ZnO nano- and microstructures. AB - A viable lightweight absorber is the current need for stealth technology as well as microwave absorption. Several microwave absorbers have been developed, but it is still a challenge to fabricate an absorber that facilitates microwave absorption in broad bandwidth or covers the maximum portion of the frequency range 2-18 GHz, the commonly used range for radar and other applications. Therefore, it is highly required to develop a wide bandwidth absorber that can provide microwave absorption in the most part of the frequency range 2-18 GHz while simultaneously being lightweight and can be fabricated in desired bulk quantities by the cost-effective synthesis methods. In this paper, an attempt has been made to design an ultra-wide bandwidth absorber with enhanced microwave absorption response by using nickel-phosphorus coated tetrapod-shaped ZnO (Ni-P coated T-ZnO). In the Ni-P coated T-ZnO absorber, ZnO acts as a good dielectric contributor, while Ni as a magnetic constituent to obtain a microwave absorbing composite material, which has favorable absorption properties. Ni-P coated ZnO nano-microstructures are synthesized by a simple and scalable two-step process. First, tetrapod-shaped ZnO (T-ZnO) structures have been grown by the flame transport synthesis (FTS) approach in a single step process and then they have been coated with Ni-P by an electroless coating technique. Their morphology, degree of crystallinity and existing phases were studied in detail by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray diffraction (XRD) techniques. The complex permittivity and permeability of the "as-fabricated" T-ZnO and Ni-P coated T-ZnO have been measured in the frequency range of 4-14 GHz and their microwave absorption properties are computed using the coaxial transmission-reflection method. The strongest reflection loss (RL) peak value of -36.41 dB has been obtained at a frequency of ~8.99 GHz with coating thickness of 3.4 mm for the Ni-P coated T-ZnO sample with a broad bandwidth of 10.0 GHz (RL < -10 dB) in the frequency range of 4.0-14.0 GHz. PMID- 26267360 TI - Improving Cancer Chemoradiotherapy Treatment by Dual Controlled Release of Wortmannin and Docetaxel in Polymeric Nanoparticles. AB - Combining molecularly targeted agents and chemotherapeutics is an emerging strategy in cancer treatment. We engineered sub-50 nm diameter diblock copolymer nanoparticles (NPs) that can sequentially release wortmannin (Wtmn, a cell signaling inhibitor) and docetaxel (Dtxl, genotoxic anticancer agent) to cancer cells. These NPs were studied in chemoradiotherapy, an important cancer treatment paradigm, in the preclinical setting. We demonstrated that Wtmn enhanced the therapeutic efficacy of Dtxl and increased the efficiency of radiotherapy (XRT) in H460 lung cancer and PC3 prostate cells in culture. Importantly, we showed that NPs containing both Wtmn and Dtxl release the drugs in a desirable sequential fashion to maximize therapeutic efficacy in comparison to administering each drug alone. An in vivo toxicity study in a murine model validated that NPs containing both Dtxl and Wtmn do not have a high toxicity profile. Lastly, we demonstrated that Dtxl/Wtmn-coencapsulated NPs are more efficient than each single-drug-loaded NPs or a combination of both single-drug loaded NPs in chemoradiotherapy using xenograft models. Histopathological studies and correlative studies support that the improved therapeutic efficacy is through changes in signaling pathways and increased tumor cell apoptosis. Our findings suggest that our nanoparticle system led to a dynamic rewiring of cellular apoptotic pathways and thus improve the therapeutic efficiency. PMID- 26267362 TI - Differential Structural Development of Adult-Born Septal Hippocampal Granule Cells in the Thy1-GFP Mouse, Nuclear Size as a New Index of Maturation. AB - Adult neurogenesis is frequently studied in the mouse hippocampus. We examined the morphological development of adult-born, immature granule cells in the suprapyramidal blade of the septal dentate gyrus over the period of 7-77 days after mitosis with BrdU-labeling in 6-weeks-old male Thy1-GFP mice. As Thy1-GFP expression was restricted to maturated granule cells, it was combined with doublecortin-immunolabeling of immature granule cells. We developed a novel classification system that is easily applicable and enables objective and direct categorization of newborn granule cells based on the degree of dendritic development in relation to the layer specificity of the dentate gyrus. The structural development of adult-generated granule cells was correlated with age, albeit with notable differences in the time course of development between individual cells. In addition, the size of the nucleus, immunolabeled with the granule cell specific marker Prospero-related homeobox 1 gene, was a stable indicator of the degree of a cell's structural maturation and could be used as a straightforward parameter of granule cell development. Therefore, further studies could employ our doublecortin-staging system and nuclear size measurement to perform investigations of morphological development in combination with functional studies of adult-born granule cells. Furthermore, the Thy1-GFP transgenic mouse model can be used as an additional investigation tool because the reporter gene labels granule cells that are 4 weeks or older, while very young cells could be visualized through the immature marker doublecortin. This will enable comparison studies regarding the structure and function between young immature and older matured granule cells. PMID- 26267363 TI - Cortical Granule Exocytosis Is Mediated by Alpha-SNAP and N-Ethilmaleimide Sensitive Factor in Mouse Oocytes. AB - Cortical granule exocytosis (CGE), also known as cortical reaction, is a calcium- regulated secretion that represents a membrane fusion process during meiotic cell division of oocytes. The molecular mechanism of membrane fusion during CGE is still poorly understood and is thought to be mediated by the SNARE pathway; nevertheless, it is unkown if SNAP (acronym for soluble NSF attachment protein) and NSF (acronym for N-ethilmaleimide sensitive factor), two key proteins in the SNARE pathway, mediate CGE in any oocyte model. In this paper, we documented the gene expression of alpha-SNAP, gamma-SNAP and NSF in mouse oocytes. Western blot analysis showed that the expression of these proteins maintains a similar level during oocyte maturation and early activation. Their localization was mainly observed at the cortical region of metaphase II oocytes, which is enriched in cortical granules. To evaluate the function of these proteins in CGE we set up a functional assay based on the quantification of cortical granules metaphase II oocytes activated parthenogenetically with strontium. Endogenous alpha-SNAP and NSF proteins were perturbed by microinjection of recombinant proteins or antibodies prior to CGE activation. The microinjection of wild type alpha-SNAP and the negative mutant of alpha-SNAP L294A in metaphase II oocytes inhibited CGE stimulated by strontium. NEM, an irreversibly inhibitor of NSF, and the microinjection of the negative mutant NSF D1EQ inhibited cortical reaction. The microinjection of anti-alpha-SNAP and anti-NSF antibodies was able to abolish CGE in activated metaphase II oocytes. The microinjection of anti-gamma SNAP antibody had no effect on CGE. Our findings indicate, for the first time in any oocyte model, that alpha-SNAP, gamma-SNAP, and NSF are expressed in mouse oocytes. We demonstrate that alpha-SNAP and NSF have an active role in CGE and propose a working model. PMID- 26267364 TI - In vivo photoacoustic flowmetry at depths of the diffusive regime based on saline injection. AB - We propose a saline injection-based method to quantify blood flow velocity in vivo with acoustic-resolution photoacoustic tomography. By monitoring the saline blood interface propagating in the blood vessel, the flow velocity can be resolved. We first demonstrated our method in phantom experiments, where a root mean square error of prediction of 0.29 mm/s was achieved. By injecting saline into a mouse tail vein covered with 1 mm chicken tissue, we showed that the flow velocity in the tail vein could be measured at depths, which is especially pertinent to monitoring blood flow velocity in patients undergoing intravenous infusion. PMID- 26267365 TI - Hybrid Structure of the Type 1 Pilus of Uropathogenic Escherichia coli. AB - Type 1 pili are filamentous protein assemblies on the surface of Gram-negative bacteria that mediate adhesion to host cells during the infection process. The molecular structure of type 1 pili remains elusive on the atomic scale owing to their insolubility and noncrystallinity. Herein we describe an approach for hybrid-structure determination that is based on data from solution-state NMR spectroscopy on the soluble subunit and solid-state NMR spectroscopy and STEM data on the assembled pilus. Our approach is based on iterative modeling driven by structural information extracted from different sources and provides a general tool to access pseudo atomic structures of protein assemblies with complex subunit folds. By using this methodology, we determined the local conformation of the FimA pilus subunit in the context of the assembled type 1 pilus, determined the exact helical pilus architecture, and elucidated the intermolecular interfaces contributing to pilus assembly and stability with atomic detail. PMID- 26267366 TI - An Evaluation of the Italian Version of the Yale Food Addiction Scale in Obese Adult Inpatients Engaged in a 1-Month-Weight-Loss Treatment. AB - Addiction is a compulsive need for and use of a specific substance leading to a habit, tolerance, and psychophysiological symptoms. Excessive food consumption is similar to that of substance addiction. Some individuals who have trouble losing weight display addictive eating symptoms. To investigate food addiction in a sample of obese adults referred to hospital for a 1-month-weight-loss treatment. The Italian version of the Yale Food Addiction Scale (YFAS-16) was used as a screening tool in 88 obese inpatients. The construct validity of the YFAS-16 was assessed by testing its correlations with measures of binge eating (Binge Eating Scale), impulsiveness (Barratt Impulsiveness Scale), and emotional dysregulation (Difficulties in Emotion Regulation Scale). 34.1% of our sample was diagnosed with YFAS food addiction. Such diagnosis was also supported by strong associations between FA and psychological and behavioral features, typically descriptive of classic addiction. Patients who endorsed the YFAS-16 criteria for food addiction (FA) had significantly higher binge eating levels, greater emotional dysregulation, and nonacceptance of negative feelings; they lacked goal oriented behavior, had little impulse control, had difficulty in emotion recognition, and attentional impulsivity; and they were unable to concentrate and lacked inhibitory control behavior, unlike participants who did not meet the FA criteria. Further research is needed to support the reliability of the YFAS-16. This measure has the potential to be applied in epidemiological research, estimating the prevalence of FA within the Italian population and to assess new treatments' efficacy for obese patients with food addiction symptoms seeking weight-loss treatments. PMID- 26267368 TI - Dendrimer-Linked Antifreeze Proteins Have Superior Activity and Thermal Recovery. AB - By binding to ice, antifreeze proteins (AFPs) depress the freezing point of a solution and inhibit ice recrystallization if freezing does occur. Previous work showed that the activity of an AFP was incrementally increased by fusing it to another protein. Even larger increases in activity were achieved by doubling the number of ice-binding sites by dimerization. Here, we have combined the two strategies by linking multiple outward-facing AFPs to a dendrimer to significantly increase both the size of the molecule and the number of ice binding sites. Using a heterobifunctional cross-linker, we attached between 6 and 11 type III AFPs to a second-generation polyamidoamine (G2-PAMAM) dendrimer with 16 reactive termini. This heterogeneous sample of dendrimer-linked type III constructs showed a greater than 4-fold increase in freezing point depression over that of monomeric type III AFP. This multimerized AFP was particularly effective at ice recrystallization inhibition activity, likely because it can simultaneously bind multiple ice surfaces. Additionally, attachment to the dendrimer has afforded the AFP superior recovery from heat denaturation. Linking AFPs together via polymers can generate novel reagents for controlling ice growth and recrystallization. PMID- 26267372 TI - Analysis of Drugs in Unconventional Samples. AB - Forensic scientists have long detected the presence of drugs in biological materials using body fluids such as urine, blood, and/or tissues. In recent years, remarkable advances in sensitive analytical techniques have prompted the analysis of drugs in unconventional biological samples such as hair, nail, saliva, and sweat. These samples are easily collected, although drug levels are often lower than the corresponding urine, blood, or tissue levels. This article reviews studies on the detection of drugs of abuse in hair, nail, saliva, and sweat. Preparation or pretreatment of samples, analytical procedures, and the interpretation of analytical results are discussed concomitantly.. PMID- 26267367 TI - Flexibility and extracellular opening determine the interaction between ligands and insect sulfakinin receptors. AB - Despite their fundamental importance for growth, the mechanisms that regulate food intake are poorly understood. Our previous work demonstrated that insect sulfakinin (SK) signaling is involved in inhibiting feeding in an important model and pest insect, the red flour beetle Tribolium castaneum. Because the interaction of SK peptide and SK receptors (SKR) initiates the SK signaling, we have special interest on the structural factors that influence the SK-SKR interaction. First, the three-dimensional structures of the two T. castaneum SKRs (TcSKR1 and TcSKR2) were generated from molecular modeling and they displayed significance in terms of the outer opening of the cavity and protein flexibility. TcSKR1 contained a larger outer opening of the cavity than that in TcSKR2, which allows ligands a deep access into the cavity through cell membrane. Second, normal mode analysis revealed that TcSKR1 was more flexible than TcSKR2 during receptor-ligand interaction. Third, the sulfated SK (sSK) and sSK-related peptides were more potent than the nonsulfated SK, suggesting the importance of the sulfate moiety. PMID- 26267373 TI - The Current Legal Status of Drug Testing and Its Implications. AB - Current U.S. law on drug testing is reviewed in this article. The widespread practices of drug abuse and drug testing in the United States are reviewed in the initial section. Legal questions are posed concerning constitutional rights and the rights organized labor has won in the courts during the last century. Federal appellate case law, federal and state statutory law, and military law on drug testing issues are examined in the context of their impact on public, private, criminal justice, and military sectors of American society. Future legal trends on drug testing are predicted in the conclusion. PMID- 26267374 TI - Development and Current Status of Skull-Image Superimposition - Methodology and Instrumentation. AB - This article presents a review of the literature and an evaluation on the development and application of skull-image superimposition technology - both instrumentation and methodology - contributed by a number of scholars since 1935. Along with a comparison of the methodologies involved in the two superimposition techniques - photographic and video - the author characterized the techniques in action and the recent advances in computer image superimposition processing technology. The major disadvantage of conventional approaches is its relying on subjective interpretation. Through painstaking comparison and analysis, computer image processing technology can make more conclusive identifications by direct testing and evaluating the various programmed indices. PMID- 26267375 TI - Impurities in Illicit Drug Preparations: 3,4-(Methylenedioxy)amphetamine and 3,4 (Methylenedioxy)methylamphetamine. AB - Attention is given here to the mass spectral data of impurities present in illicit drug preparations of 3,4-(methylenedioxy)amphetamine and 3,4 (methylenedioxy)methylamphetamine. These "designer" drugs, having emphatic properties, were synthesized following well-known procedures such as the reductive amination route, the Leuckart reaction, and the nitropropene and the bromopropane routes. Based on the structure elucidation of impurities - especially those so-called "route specific" ones - present in these illicit drug preparations conclusions can be drawn about the method of preparation of a drug sample. Furthermore, on the basis of this kind of information methods can be developed for the comparison of drug samples, by which questions about the origin of drug samples can be solved (commonly known as the signature method). PMID- 26267376 TI - Assessments of Thioridazine as a Helper Compound to Dicloxacillin against Methicillin-Resistant Staphylococcus aureus: In Vivo Trials in a Mouse Peritonitis Model. AB - INTRODUCTION: The rise in antimicrobial resistance is a major global concern and requires new treatment strategies. The use of helper compounds, such as thioridazine (TDZ), an antipsychotic drug, in combination with traditional antibiotics must be investigated. OBJECTIVES: The aim of this study was to investigate the efficacy of TDZ as a helper compound for dicloxacillin (DCX) against methicillin-resistant Staphylococcus aureus (MRSA) in vivo, and compare the combination treatment of DCX+TDZ with vancomycin (VAN). METHODS: Mice were inoculated with an intraperitoneal (IP) injection of MRSA (108 CFU) and treated in a 12-hour cycle for 48 hours. By termination, bacterial quantities in a peritoneal flush, spleen and kidneys were obtained. In the main trial the drugs were administered subcutaneously in five treatment groups: 1) DCX, 2) TDZ, 3) DCX+TDZ, 4) VAN, 5) SALINE. Additional smaller studies with IP administration and higher subcutaneous dosages (*1.5 and *4) of the drugs were subsequently performed. RESULTS: In the main trial no significant differences were found between DCX+TDZ and DCX or TDZ alone (p>=0.121-0.999). VAN performed significantly better than DCX+TDZ on all bacteriological endpoints (p<0.001). Higher subcutaneous dosages of DCX and TDZ improved the antibacterial efficacy, but the combination treatment was still not significantly better than monotherapy. IP drug administration of DCX+TDZ revealed a significantly better antibacterial effect than DCX or TDZ alone (p<0.001) but not significantly different from VAN (p>0.999). CONCLUSION: In conclusion, TDZ did not prove to be a viable helper compound for dicloxacillin against MRSA in subcutaneous systemic treatment. However, IP-administration of DCX+TDZ, directly at the infection site resulted in a synergetic effect, with efficacy comparable to that of VAN. PMID- 26267377 TI - A hybrid color space for skin detection using genetic algorithm heuristic search and principal component analysis technique. AB - Color is one of the most prominent features of an image and used in many skin and face detection applications. Color space transformation is widely used by researchers to improve face and skin detection performance. Despite the substantial research efforts in this area, choosing a proper color space in terms of skin and face classification performance which can address issues like illumination variations, various camera characteristics and diversity in skin color tones has remained an open issue. This research proposes a new three dimensional hybrid color space termed SKN by employing the Genetic Algorithm heuristic and Principal Component Analysis to find the optimal representation of human skin color in over seventeen existing color spaces. Genetic Algorithm heuristic is used to find the optimal color component combination setup in terms of skin detection accuracy while the Principal Component Analysis projects the optimal Genetic Algorithm solution to a less complex dimension. Pixel wise skin detection was used to evaluate the performance of the proposed color space. We have employed four classifiers including Random Forest, Naive Bayes, Support Vector Machine and Multilayer Perceptron in order to generate the human skin color predictive model. The proposed color space was compared to some existing color spaces and shows superior results in terms of pixel-wise skin detection accuracy. Experimental results show that by using Random Forest classifier, the proposed SKN color space obtained an average F-score and True Positive Rate of 0.953 and False Positive Rate of 0.0482 which outperformed the existing color spaces in terms of pixel wise skin detection accuracy. The results also indicate that among the classifiers used in this study, Random Forest is the most suitable classifier for pixel wise skin detection applications. PMID- 26267378 TI - Implicit Goalkeeper Influences on Goal Side Selection in Representative Penalty Kicking Tasks. AB - In well-controlled lab situations, marginal displacements of the goalkeeper on the goal line affect goal side selection of penalty takers implicitly, that is, without the penalty takers being consciously aware of the displacement. Whether this effect is retained in more representative real-life situations with competing goalkeepers and penalty takers has not been verified. In the current study, penalty takers were instructed to position the goalkeepers at the centre of the goal. They then performed penalty kicks adopting either a keeper independent or a keeper dependent strategy, while goalkeepers actually attempted to save the ball by strategically diving early or late. Analyses of trials in which penalty takers failed to place the goalkeeper in the centre of the goal (although they incorrectly believed they placed the goalkeeper at the centre of the goal) showed that implicit influences of the goalkeeper's position on goal side selection were overridden by the (conscious) perception of the direction of the goalkeeper's dive, but only if the penalty takers deliberately monitored the goalkeeper's action and the goalkeeper committed early enough for penalty takers to respond. In all other combinations of penalty kick and goalkeeper strategies more than 60% of the kicks were directed to the side of the goal with more space. Most importantly, however, the current study shows that influences of implicit perception on the penalty takers' decision making are rather pervasive considering that many supraliminal sources of information were available. That is, the current study demonstrates that implicit perception retains its influence on decision-making even if other (stronger) stimuli are also present. PMID- 26267379 TI - Morphological Characterization of the Action Potential Initiation Segment in GnRH Neuron Dendrites and Axons of Male Mice. AB - GnRH neurons are the final output neurons of the hypothalamic network controlling fertility in mammals. In the present study, we used ankyrin G immunohistochemistry and neurobiotin filling of live GnRH neurons in brain slices from GnRH-green fluorescent protein transgenic male mice to examine in detail the location of action potential initiation in GnRH neurons with somata residing at different locations in the basal forebrain. We found that the vast majority of GnRH neurons are bipolar in morphology, elaborating a thick (primary) and thinner (secondary) dendrite from opposite poles of the soma. In addition, an axon-like process arising predominantly from a proximal dendrite was observed in a subpopulation of GnRH neurons. Ankyrin G immunohistochemistry revealed the presence of a single action potential initiation zone ~27 MUm in length primarily in the secondary dendrite of GnRH neurons and located 30 to 140 MUm distant from the cell soma, depending on the type of process and location of the cell body. In addition to dendrites, the GnRH neurons with cell bodies located close to hypothalamic circumventricular organs often elaborated ankyrin G-positive axon like structures. Almost all GnRH neurons (>90%) had their action potential initiation site in a process that initially, or ultimately after a hairpin loop, was coursing in the direction of the median eminence. These studies indicate that action potentials are initiated in different dendritic and axonal compartments of the GnRH neuron in a manner that is dependent partly on the neuroanatomical location of the cell body. PMID- 26267380 TI - Inhibitory Effect of the Noncamptothecin Topoisomerase I Inhibitor LMP-400 on Female Mice Models and Human Pheochromocytoma Cells. AB - Metastatic pheochromocytoma continues to be an incurable disease, and treatment with conventional cytotoxic chemotherapy offers limited efficacy. In the present study, we evaluated a novel topoisomerase I inhibitor, LMP-400, as a potential treatment for this devastating disease. We found a high expression of topoisomerase I in human metastatic pheochromocytoma, providing a basis for the evaluation of a topoisomerase 1 inhibitor as a therapeutic strategy. LMP-400 inhibited the cell growth of established mouse pheochromocytoma cell lines and primary human tumor tissue cultures. In a study performed in athymic female mice, LMP-400 demonstrated a significant inhibitory effect on tumor growth with two drug administration regimens. Furthermore, low doses of LMP-400 decreased the protein levels of hypoxia-inducible factor 1 (HIF-1alpha), one of a family of factors studied as potential metastatic drivers in these tumors. The HIF-1alpha decrease resulted in changes in the mRNA levels of HIF-1 transcriptional targets. In vitro, LMP-400 showed an increase in the growth-inhibitory effects in combination with other chemotherapeutic drugs that are currently used for the treatment of pheochromocytoma. We conclude that LMP-400 has promising antitumor activity in preclinical models of metastatic pheochromocytoma and its use should be considered in future clinical trials. PMID- 26267382 TI - Extreme food-plant specialisation in Megabombus bumblebees as a product of long tongues combined with short nesting seasons. AB - Megabombus bumblebees have unusually long tongues and are generally more specialised than other bumblebees in their choice of food plants. The phylogeny of Megabombus bumblebees shows that speciation was concentrated in two periods. Speciation in the first period (ca 4.25-1.5 Ma) is associated with the late rise of the Hengduan Mountains at the eastern end of the Qinghai-Tibetan plateau. Speciation in the second period (1.2-0.3 Ma) is associated with climatic cooling in the northern forests. The most extreme food-specialist species belong to the second period, which may point to climate as a factor in specialisation. These extreme specialist species occur either in the far north (Bombus consobrinus), or at high elevations (Bombus gerstaeckeri), in situations where long tongues coincide with the shortest nesting seasons. Species with the longest tongues but occurring further south (even at high elevations) use a broader range of food plants. PMID- 26267383 TI - Design and Synthesis of Non-Peptide, Selective Orexin Receptor 2 Agonists. AB - Orexins are a family of neuropeptides that regulate sleep/wakefulness, acting on two G-protein-coupled receptors, orexin receptors 1 (OX1R) and 2 (OX2R). Genetic and pharmacologic evidence suggests that orexin receptor agonists, especially OX2R agonist, will be useful for mechanistic therapy of the sleep disorder narcolepsy/cataplexy. We herein report the discovery of a potent (EC50 on OX2R is 0.023 MUM) and OX2R-selective (OX1R/OX2R EC50 ratio is 70) agonist, 4'-methoxy N,N-dimethyl-3'-[N-(3-{[2-(3-methylbenzamido)ethyl]amino}phenyl)sulfamoyl]-(1,1' biphenyl)-3-carboxamide 26. PMID- 26267384 TI - Recent advances in the chemical physics of nanoalloys. PMID- 26267381 TI - Molecular Basis of Gene-Gene Interaction: Cyclic Cross-Regulation of Gene Expression and Post-GWAS Gene-Gene Interaction Involved in Atrial Fibrillation. AB - Atrial fibrillation (AF) is the most common cardiac arrhythmia at the clinic. Recent GWAS identified several variants associated with AF, but they account for <10% of heritability. Gene-gene interaction is assumed to account for a significant portion of missing heritability. Among GWAS loci for AF, only three were replicated in the Chinese Han population, including SNP rs2106261 (G/A substitution) in ZFHX3, rs2200733 (C/T substitution) near PITX2c, and rs3807989 (A/G substitution) in CAV1. Thus, we analyzed the interaction among these three AF loci. We demonstrated significant interaction between rs2106261 and rs2200733 in three independent populations and combined population with 2,020 cases/5,315 controls. Compared to non-risk genotype GGCC, two-locus risk genotype AATT showed the highest odds ratio in three independent populations and the combined population (OR=5.36 (95% CI 3.87-7.43), P=8.00*10-24). The OR of 5.36 for AATT was significantly higher than the combined OR of 3.31 for both GGTT and AACC, suggesting a synergistic interaction between rs2106261 and rs2200733. Relative excess risk due to interaction (RERI) analysis also revealed significant interaction between rs2106261 and rs2200733 when exposed two copies of risk alleles (RERI=2.87, P<1.00*10-4) or exposed to one additional copy of risk allele (RERI=1.29, P<1.00*10-4). The INTERSNP program identified significant genotypic interaction between rs2106261 and rs2200733 under an additive by additive model (OR=0.85, 95% CI: 0.74-0.97, P=0.02). Mechanistically, PITX2c negatively regulates expression of miR-1, which negatively regulates expression of ZFHX3, resulting in a positive regulation of ZFHX3 by PITX2c; ZFHX3 positively regulates expression of PITX2C, resulting in a cyclic loop of cross-regulation between ZFHX3 and PITX2c. Both ZFHX3 and PITX2c regulate expression of NPPA, TBX5 and NKX2.5. These results suggest that cyclic cross-regulation of gene expression is a molecular basis for gene-gene interactions involved in genetics of complex disease traits. PMID- 26267385 TI - A note from the Editor's desk. PMID- 26267386 TI - Advanced and In Situ Analytical Methods for Solar Fuel Materials. AB - In situ and operando techniques can play important roles in the development of better performing photoelectrodes, photocatalysts, and electrocatalysts by helping to elucidate crucial intermediates and mechanistic steps. The development of high throughput screening methods has also accelerated the evaluation of relevant photoelectrochemical and electrochemical properties for new solar fuel materials. In this chapter, several in situ and high throughput characterization tools are discussed in detail along with their impact on our understanding of solar fuel materials. PMID- 26267387 TI - How we approach a patient with symptoms of leukostasis requiring emergent leukocytapheresis. AB - Hyperleukocytosis can induce leukostasis, which can lead to vascular obstructions (usually in the lungs and central nervous system), tumor lysis syndrome, and disseminated intravascular coagulation. Although it has not been conclusively shown to improve long-term outcome, leukocytapheresis may be used as part of the management of hyperleukocytosis with or without leukostasis to rapidly reduce the white blood cell (WBC) burden. Since leukocytapheresis only temporarily decreases the WBC count, early initiation of more definite therapy, such as hydroxyurea and/or chemotherapy, is essential. In this article, clinical assessment of the patient's clinical status to determine the need for leukocytapheresis as well as a general guideline for management of the technical aspects and complications of the procedure are discussed. PMID- 26267388 TI - Controlling dimensionality via a dual ligand strategy in Ln-thiophene-2,5 dicarboxylic acid-terpyridine coordination polymers. AB - Eleven new lanthanide (Ln = Nd-Lu)-thiophene-2,5-dicarboxylic acid (25-TDC) 2,2':6',2''-terpyridine (terpy) coordination polymers () which employ a dual ligand strategy have been synthesized hydrothermally and structurally characterized by single crystal and powder X-ray diffraction. Two additional members of the series ( and ) were made with Ce(3+) and Pr(3+) and characterized via powder X-ray diffraction only. The series is comprised of three similar structures wherein differences due to the lanthanide contraction manifest in Ln(3+) coordination number as well as the number of bound and solvent water molecules within the crystal lattice. Structure type I (Ce(3+)-Sm(3+)) contains two nine-coordinate Ln(3+) metal centers each with a bound water molecule. Structure type II (Eu(3+)-Ho(3+)) features a nine and an eight coordinate Ln(3+) metal along with one bound and one solvent water molecule. Structure type III (Er(3+)-Lu(3+)) includes two eight-coordinate Ln(3+) metal centers with both water molecules residing in the lattice. Assembly into supramolecular 3D networks via pi-pi interactions is observed for all three structure types, whereas structure types II and III also feature hydrogen-bonding interactions via the well-known C-HO and O-HO synthons. Visible and near-IR luminescence studies were performed on compounds , , , and at room temperature. As a result characteristic near-IR luminescent bands of Pr(3+), Nd(3+), Sm(3+), and Yb(3+) as well as visible bands of Sm(3+) were observed. PMID- 26267389 TI - Multistep Molecular Dynamics Simulations Identify the Highly Cooperative Activity of Melittin in Recognizing and Stabilizing Membrane Pores. AB - The prototypical antimicrobial peptide, melittin, is well-known for its ability to induce pores in zwitterionic model lipid membranes. However, the mechanism by which melittin accomplishes this is not fully understood. We have conducted all atom and coarse-grained molecular dynamics simulations which suggest that melittin employs a highly cooperative mechanism for the induction of both small and large membrane pores. The process by which this peptide induces membrane pores appears to be driven by its affinity to membrane defects via its N-terminus region. In our simulations, a membrane defect was deliberately created through either lipid flip-flop or the reorientation of one adsorbed melittin peptide. In a cooperative response, other melittin molecules also inserted their N-termini into the created defect, thus lowering the overall free energy. The insertion of these peptide molecules ultimately allowed the defect to develop into a small transmembrane pore, with an estimated diameter of ~1.5 nm and a lifetime of the order of tens of milliseconds. In the presence of a finite membrane tension, we show that this small pore can act as a nucleation site for the stochastic rupture of the lipid bilayer, so as to create a much larger pore. We found that a threshold membrane tension of 25 mN/m was needed to create a ruptured pore. Furthermore, by actively accumulating at its edge, adsorbed peptides are able to cooperatively stabilize this larger pore. The defect-mediated pore formation mechanism revealed in this work may also apply to other amphipathic membrane active peptides. PMID- 26267390 TI - The Family Check Up and Adolescent Depression: An Examination of Treatment Responders and Non-Responders. AB - The Family Check Up (FCU) is a family-centered intervention for reducing children's problem behavior through improving parenting skills and family interactions. Although the FCU was designed to prevent conduct problems, we have also found the program to be effective in preventing escalating symptoms of depression in early adolescence. The current analyses examine heterogeneous patterns of response to treatment in an effort to identify factors associated with differential response to family intervention. We examined heterogeneity in trajectories of youth-reported depressive symptoms from grades 6 to 9, using a Latent Growth Mixture Modeling framework to identify patterns of treatment response and non-response. Three symptom trajectories were identified, including the following: (1) a large class exhibiting stable, low symptom levels, (2) a class exhibiting high and stable depressive symptoms, and (3) a class exhibiting low initial symptoms that increased over time. Significant intervention effects were identified only among the third class, as a preventive effect on depression from 7th to 9th grade for youth with low initial symptoms. No effect of intervention was observed in the other two classes. Comparisons of classes 2 and 3 suggested that class 3 members were more likely to be females with high baseline antisocial behavior, but lower initial levels of depression. The findings suggest the importance of exploring heterogeneity within a prevention design, as well as the importance of tailored approaches to the prevention of adolescent depression. PMID- 26267391 TI - Characterization of the superoxide dismutase genes of the halophyte Suaeda maritima in Japan and Egypt. AB - KEY MESSAGE: Suaeda maritima varieties native to Japan and Egypt were cultured under aseptic conditions. The varieties differed in genetic distance but exhibited similar expression profiles of superoxide dismutase isozyme genes. The expression characteristics of superoxide dismutase (SOD; EC 1.15.1.1) isozyme genes from halophytic Suaeda marit ima plants native to Japan and Egypt were analyzed using young plants grown under aseptic conditions. A phylogenetic tree based on internal transcribed spacer sequences suggested that Egyptian S. maritima is related to European and India S. maritima, while Japanese S. maritima belongs to a separate clade. An in-gel SOD activity staining assay revealed that leaves from both the Egyptian and Japanese varieties showed high levels of CuZn SOD and Fe-SOD activity, but no Mn-SOD activity; conversely, stems from both varieties showed Mn-SOD activity as well as other SOD isozyme activities. In Japanese S. maritima leaves, SOD activity was increased by incubation in growth medium containing 400 mM NaCl, while Egyptian S. maritima leaves showed elevated SOD activity in the absence of high salt. Genes encoding Mn-SOD and Fe-SOD were isolated from both plant types. RT-PCR analysis revealed that all SOD isozyme encoding genes were expressed at the same levels in leaves from both plant types grown in normal or high-salt medium. In contrast, the expression of genes encoding choline monooxygenase and betaine aldehyde dehydrogenase, which are involved in betacyanin biosynthesis, was increased in high-salt medium. In leaves of Japanese S. maritima plants, Fe deficiency without high salt exposure preferentially decreased Fe-SOD activity. On the other hand, Fe deficiency with high salt exposure decreased not only Fe-SOD activity but also CuZn-SOD activity, suggesting that Fe availability is involved in the up-regulation of SOD isozymes mediating salt tolerance. PMID- 26267392 TI - CRISPR EATING on a Low Budget. AB - In this issue of Developmental Cell, Lane et al. (2015) describe a simplified, inexpensive technique named "CRISPR EATING" for generating complex guide RNA libraries suitable for CRISPR/Cas9-based applications ranging from genome visualization and manipulation to genetic screens. PMID- 26267394 TI - In Situ Synthesis of Porous Carbons by Using Room-Temperature, Atmospheric Pressure Dielectric Barrier Discharge Plasma as High-Performance Adsorbents for Solid-Phase Microextraction. AB - A one-step, template-free method is described to synthesize porous carbons (PCs) in situ on a metal surface by using a room-temperature, atmospheric-pressure dielectric barrier discharge (DBD) plasma. This method not only features high efficiency, environmentally friendliness, and low cost and simple equipment, but also can conveniently realize large-area synthesis of PCs by only changing the design of the DBD reactor. The synthesized PCs have a regulated nestlike morphology, and thus, provide a high specific surface area and high pore volume, which result in excellent adsorption properties. Its applicability was demonstrated by using a PC-coated stainless-steel fiber as a solid-phase microextraction (SPME) fiber to preconcentrate polycyclic aromatic hydrocarbons (PAHs) prior to analysis by gas chromatography with flame ionization detection (GC-FID). The results showed that the fiber exhibited excellent enrichment factors (4.1*10(4) to 3.1*10(5)) toward all tested PAHs. Thus, the PC-based SPME GC-FID provides low limits of detection (2 to 20 ng L(-1)), good precision (<7.8%), and good recoveries (80-115%) for ultra-sensitive determination of PAHs in real water samples. In addition, the PC-coated fiber could be stable enough for more than 500 replicate extraction cycles. PMID- 26267393 TI - Organ Size Control: Lessons from Drosophila. AB - Of fundamental interest to biologists is how organs achieve a reproducible size during development. Studies of the developing Drosophila wing have provided many key insights that will help give a conceptual understanding of the process beyond the fly. In the wing, there is evidence for both "top-down" mechanisms, in which signals emanating from small subsets of cells direct global proliferation, and "bottom-up" mechanisms, in which the final size is an emergent property of local cell-cell interactions. Mechanical forces also appear to have an important role along with the Hippo pathway, which may integrate multiple types of inputs to regulate the extent of growth. PMID- 26267395 TI - Cartilage Regeneration in the Head and Neck Area: Combination of Ear or Nasal Chondrocytes and Mesenchymal Stem Cells Improves Cartilage Production. AB - BACKGROUND: Cartilage tissue engineering can offer promising solutions for restoring cartilage defects in the head and neck area and has the potential to overcome limitations of current treatments. However, to generate a construct of reasonable size, large numbers of chondrocytes are required, which limits its current applicability. Therefore, the authors evaluate the suitability of a combination of cells for cartilage regeneration: bone marrow-derived mesenchymal stem cells and ear or nasal chondrocytes. METHODS: Human bone marrow-derived mesenchymal stem cells were encapsulated in alginate hydrogel as single-cell-type populations or in combination with bovine ear chondrocytes or nasal chondrocytes at an 80:20 ratio. Constructs were either cultured in vitro or implanted directly subcutaneously into mice. Cartilage formation was evaluated with biochemical and biomechanical analyses. The use of a xenogeneic coculture system enabled the analyses of the contribution of the individual cell types using species-specific gene-expression analyses. RESULTS: In vivo, human bone marrow-derived mesenchymal stem cells/bovine ear chondrocytes or human bone marrow-derived mesenchymal stem cells/bovine nasal chondrocytes contained amounts of cartilage components similar to those of constructs containing chondrocytes only (i.e., bovine ear and nasal chondrocytes). In vitro, species-specific gene-expression analyses demonstrated that aggrecan was expressed by the chondrocytes only, which suggests a more trophic role for human bone marrow-derived mesenchymal stem cells. Furthermore, the additional effect of human bone marrow-derived mesenchymal stem cells was more pronounced in combination with bovine nasal chondrocytes. CONCLUSIONS: By supplementing low numbers of bovine ear or nasal chondrocytes with human bone marrow-derived mesenchymal stem cells, the authors were able to engineer cartilage constructs with properties similar to those of constructs containing chondrocytes only. This makes the procedure more feasible for future applicability in the reconstruction of cartilage defects in the head and neck area because fewer chondrocytes are required. PMID- 26267396 TI - Physical and Functional Ability Recovery Patterns and Quality of Life after Immediate Autologous Latissimus Dorsi Breast Reconstruction: A 1-Year Prospective Observational Study. AB - BACKGROUND: The authors evaluated arm and shoulder function and quality of life prospectively after breast reconstruction with the latissimus dorsi flap. METHODS: Muscle strength was checked by manual muscle test and range of motion preoperatively and then at five postoperative time points: week 2, week 6, month 3, month 6, and month 12. Functional disability and quality of life were also measured by the Disabilities of the Arm, Shoulder and Hand questionnaire and the 36-Item Short-Form Health Survey. The assessments were performed preoperatively and then at three postoperative time-points (i.e., months 3, 6, and 12). Statistical analysis was performed by repeated-measures analysis of variance. RESULTS: Thirty-one patients were included for analysis. All manual muscle test and range-of-motion scale scores at postoperative week 2 decreased significantly compared with preoperative scores. After postoperative month 3, scores for both manual muscle test and range of motion nearly recovered to preoperative status. However, functional disability, according to the Disabilities of the Arm, Shoulder and Hand instrument, was increased considerably after latissimus dorsi flap surgery, and a substantial amount of disability remained 1 year postoperatively. The mental component of the 36-Item Short-Form Health Survey improved consistently for 1 year postoperatively, whereas the physical component decreased significantly until the sixth month postoperatively and was still lower than the preoperative score at postoperative month 12. CONCLUSIONS: One year after latissimus dorsi flap surgery, shoulder strength and range of motion returned to baseline. However, functional disability and deteriorated physical aspects of quality of life persisted. PMID- 26267397 TI - Assessing the Impact of Blood Loss in Cranial Vault Remodeling: A Risk Assessment Model Using the 2012 to 2013 Pediatric National Surgical Quality Improvement Program Data Sets. AB - BACKGROUND: Most cranial vault remodeling for craniosynostosis is associated with substantial blood loss necessitating transfusion. The transfusion of over 25 ml/kg of red blood cells has long been considered an important safety threshold and has been proposed as a potential marker of health care quality, despite a lack of evidence. The authors sought to ascertain risk factors for transfusion in cranial vault remodeling and to quantify the effect of transfusion volume on postoperative complications. METHODS: Patients who underwent complex cranial vault remodeling for craniosynostosis were identified from the Pediatric National Surgical Quality Improvement Program database. Multivariate regression models were used to identify independent risk factors for transfusion and to assess its impact on subsequent outcomes. RESULTS: One thousand fifty-nine patients met inclusion criteria. Seven hundred seventy-seven patients (73.4 percent) required a transfusion and 520 patients (49.1 percent) required a transfusion in excess of 25 ml/kg. Neither transfusion nor transfusion volume in excess of 25 ml/kg had a significant effect on postoperative outcomes. Therefore, the authors sought to determine a more meaningful threshold. The top 20 percent of transfusion volumes were greater than or equal to 45.28 ml/kg. Recursive partitioning generated a threshold of 62.52 ml/kg, which independently predicted a greater number of complications and was associated with higher odds ratios than the quintile method. A threshold of 60 ml/kg was chosen for simplicity and was independently predictive of overall complications, medical complications, and increased length of stay. CONCLUSIONS: Transfusion is common in complex cranial vault remodeling. Currently described occurrence thresholds do not accurately convey postoperative risk. Transfusion in excess of 60 ml/kg significantly increases risk for complications and length of stay in cranial vault remodeling. PMID- 26267398 TI - The Plastic Surgery Hand Curriculum. AB - BACKGROUND: Designing an effective hand rotation for plastic surgery residents is difficult. The authors address this limitation by elucidating the critical components of the hand curriculum during plastic surgery residency. METHODS: Hand questions on the Plastic Surgery In-Service Training Exam for six consecutive years (2008 to 2013) were characterized by presence of imaging, vignette setting, question taxonomy, answer domain, anatomy, and topic. Answer references were quantified by source and year of publication. RESULTS: Two hundred sixty-six questions were related to hand surgery (22.7 percent of all questions; 44.3 per year) and 61 were accompanied by an image (22.9 percent). Vignettes tended to be clinic- (50.0 percent) and emergency room-based (35.3 percent) (p < 0.001). Questions required decision-making (60.5 percent) over interpretation (25.9 percent) and recall skills (13.5 percent) (p < 0.001). Answers focused on interventions (57.5 percent) over anatomy/pathology (25.2 percent) and diagnoses (17.3 percent) (p < 0.001). Nearly half of the questions focused on the digits. The highest yield topics were trauma (35.3 percent), reconstruction (24.4 percent), and aesthetic and functional problems (14.2 percent). The Journal of Hand Surgery (American volume) (20.5 percent) and Plastic and Reconstructive Surgery (18.0 percent) were the most-cited journals, and the median publication lag was 7 years. Green's Operative Hand Surgery was the most-referenced textbook (41.8 percent). CONCLUSIONS: These results will enable trainees to study hand surgery topics with greater efficiency. Faculty can use these results to ensure that tested topics are covered during residency training. Thus, a benchmark is established to improve didactic, clinical, and operative experiences in hand surgery. PMID- 26267399 TI - The Use of Pulse Oximetry for Objective Quantification of Vascular Injuries in the Hand. AB - BACKGROUND: Efficient identification of dysvascular finger(s) following trauma is critical for triaging surgical care and optimizing patient outcomes. The authors designed a study evaluating an objective measure of digital hypoxia followed by surgical exploration and correlation with vascular injury. METHODS: Patients with lacerating or penetrating trauma to the hand or digits were examined. A pulse oximeter was applied to the injured digit, and the oxygen saturation was recorded. The nonparametric Wilcoxon rank sum test was used to assess for differences in pulse oximetry for digits with and without an ischemic-type injury that required repair. Receiver operating characteristic curve analyses were used to determine cut-points. RESULTS: Twenty patients with digital lacerations were enrolled, with a total of 49 digit measurements of pulse oximetry. Twelve dysvascular injuries requiring repair or amputation were confirmed in the operating room. There was a significant difference in pulse oximetry measurement in digits with (76 percent; 95 percent CI, 64 to 87 percent) and without (98 percent; 95 percent CI, 97 to 99 percent) ischemic injury (p < 0.001). Injured digits ranged in pulse oximetry values from 53 to 92 percent. CONCLUSIONS: Pulse oximetry is widely available and offers an objective measure of tissue oxygenation. No digit with a pulse oximetry value of at least 95 percent had an ischemic injury, and all digits with a pulse oximetry value of 84 percent or lower required operative vascular treatment. Based on these data, pulse oximetry should be adopted as a routine measure for the evaluation and communication of a potentially dysvascular digit. PMID- 26267400 TI - Comparison of Outcomes following Autologous Breast Reconstruction Using the DIEP and Pedicled TRAM Flaps: A 12-Year Clinical Retrospective Study and Literature Review. AB - BACKGROUND: There are few studies that compare the deep inferior epigastric artery perforator (DIEP) flap to the pedicled transverse rectus abdominis myocutaneous (pTRAM) flap for use in reconstructive breast surgery. The authors examined four factors that aid in decision-making: donor-site morbidity, need for surgery related to abdominal morbidity, operative time, and complications. METHODS: This is a retrospective review of patients undergoing breast reconstruction using the DIEP or pTRAM flap at the University of British Columbia between 2002 and 2013. The authors compared operative time and abdomen- and flap related complications in both groups. RESULTS: Reconstruction was performed in 507 patients; 25.6 percent received DIEP flaps (n = 183 breasts) and 74.4 percent underwent pTRAM flap surgery (n = 444 breasts). Pedicled TRAM flap patients were more likely to require abdominal closure with mesh (44.2 percent versus 8.1 percent; p < 0.001); 21.2 percent of them had a postoperative bulge and/or hernia versus 3.1 percent of DIEP flap patients; and 12.7 percent of pTRAM flap patients required surgery for hernia/bulge. Controlling for confounders, there were five times the odds of a hernia/bulge in the pTRAM flap group. DIEP flap surgery was 234 minutes longer than pTRAM flap surgery. CONCLUSIONS: The benefits of the pTRAM flap may be offset by the need to correct abdominal wall complications. DIEP flap reconstruction had lower donor complications but increased operative time. A cost analysis is needed to determine the most economical procedure. CLINCIAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 26267401 TI - Risk of Thromboembolus after Application of Different Tissue Glues during Microvascular Anastomosis. AB - BACKGROUND: Tissue glues are a useful tool for hemostasis and a potential tool for microvascular anastomosis. The hemostatic power and thrombotic risk of these surgical aids have been the subject of debate, but studies regarding thromboembolic risks of tissue glues are lacking. METHODS: The authors compared the thromboembolic risk of three different tissue glues (six interrupted sutures complemented with fibrin, FloSeal, or TachoSil) against a control group (12 interrupted sutures) in the aorta-filter model in the rat. Each group consisted of 10 rats, examined 4 hours and 14 days postoperatively (total n = 80) using a structured protocol to assess the patency and condition of the filter, amount of thromboembolic material, and histologic appearance of the vessel wall. RESULTS: In total, 160 anastomoses were performed in 80 rats. The overall patency rate for the groups was 90 percent (control), 35 percent (fibrin glue), 25 percent (FloSeal), and 10 percent (TachoSil). All experimental groups had significantly faster mean anastomotic times and less blood loss compared with the control group. Patency rates were reduced and thromboembolic material was significantly increased in all experimental groups. Histologically, the use of tissue glue reduced the incidence of irritation of the internal elastic lamina and was associated with an increased incidence of fibrocyte infiltration of the media, hypercellularity of the adventitia, and adventitial neovascularization and lymphangiogenesis. CONCLUSION: The application of tissue glues in microvascular anastomosis reduces the time needed for anastomosis but was associated with a statistically significant increase in thromboembolism. PMID- 26267402 TI - Nutrient acquisition across a dietary shift: fruit feeding butterflies crave amino acids, nectivores seek salt. AB - Evolutionary dietary shifts have major ecological consequences. One likely consequence is a change in nutrient limitation-some nutrients become more abundant in the diet, others become more scarce. Individuals' behavior should change accordingly to match this new limitation regime: they should seek out nutrients that are deficient in the new diet. We investigated the relationship between diet and responses to nutrients using adult Costa Rican butterflies with contrasting feeding habits, testing the hypothesis that animals will respond more positively to nutrients that are scarcer in their diets. Via literature searches and our own data, we showed that nitrogen and sodium are both at lower concentration in nectar than in fruit. We therefore assessed butterflies' acceptance of sodium and four nitrogenous compounds that ranged in complexity from inorganic nitrogen (ammonium chloride) to protein (albumin). We captured wild butterflies, offered them aqueous solutions of each substance, and recorded whether they accepted (drank) or rejected each substance. Support for our hypothesis was mixed. Across the sexes, frugivores were four times more likely to accept amino acids (hydrolyzed casein) than nectivores, in opposition to expectation. In males, nectivores accepted sodium almost three times more frequently than frugivores, supporting expectations. Together, these results suggest that in butterflies, becoming frugivorous is associated with an increased receptivity to amino acids and decreased receptivity to sodium. Nectivory and frugivory are widespread feeding strategies in organisms as diverse as insects, birds, and bats; our results suggest that these feeding strategies may put different pressures on how animals fulfill their nutritional requirements. PMID- 26267403 TI - Environmental tolerances of rare and common mangroves along light and salinity gradients. AB - Although mangroves possess a variety of morphological and physiological adaptations for life in a stressful habitat, interspecific differences in survival and growth under different environmental conditions can shape their local and geographic distributions. Soil salinity and light are known to affect mangrove performance, often in an interactive fashion. It has also been hypothesized that mangroves are intrinsically shade intolerant due to the high physiological cost of coping with saline flooded soils. To evaluate the relationship between stress tolerance and species distributions, we compared responses of seedlings of three widespread mangrove species and one narrow endemic mangrove species in a factorial array of light levels and soil salinities in an outdoor laboratory experiment. The more narrowly distributed species was expected to exhibit a lower tolerance of potentially stressful conditions. Two of the widespread species, Avicennia germinans and Lumnitzera racemosa, survived and grew well at low-medium salinity, regardless of light level, but performed poorly at high salinity, particularly under high light. The third widespread species, Rhizophora mangle, responded less to variation in light and salinity. However, at high salinity, its relative growth rate was low at every light level and none of these plants flushed leaves. As predicted, the rare species, Pelliciera rhizophorae, was the most sensitive to environmental stressors, suffering especially high mortality and reduced growth and quantum yield under the combined conditions of high light and medium-high salinity. That it only thrives under shaded conditions represents an important exception to the prevailing belief that halophytes are intrinsically constrained to be shade intolerant. PMID- 26267405 TI - GEANT4 for breast dosimetry: parameters optimization study. AB - Mean glandular dose (MGD) is the main dosimetric quantity in mammography. MGD evaluation is obtained by multiplying the entrance skin air kerma (ESAK) by normalized glandular dose (DgN) coefficients. While ESAK is an empirical quantity, DgN coefficients can only be estimated with Monte Carlo (MC) methods. Thus, a MC parameters benchmark is needed for effectively evaluating DgN coefficients. GEANT4 is a MC toolkit suitable for medical purposes that offers to the users several computational choices. In this work we investigate the GEANT4 performances testing the main PhysicsLists for medical applications. Four electromagnetic PhysicsLists were implemented: the linear attenuation coefficients were calculated for breast glandularity 0%, 50%, 100% in the energetic range 8-50 keV and DgN coefficients were evaluated. The results were compared with published data. Fit equations for the estimation of the G-factor parameter, introduced by the literature for converting the dose delivered in the heterogeneous medium to that in the glandular tissue, are proposed and the application of this parameter interaction-by-interaction or retrospectively is discussed. G4EmLivermorePhysicsList shows the best agreement for the linear attenuation coefficients both with theoretical values and published data. Moreover, excellent correlation factor (r2>0.99) is found for the DgN coefficients with the literature. The final goal of this study is to identify, for the first time, a benchmark of parameters that could be useful for future breast dosimetry studies with GEANT4. PMID- 26267404 TI - Roots rather than shoot residues drive soil arthropod communities of arable fields. AB - Soil food webs are driven by plant-derived carbon (C) entering the soil belowground as rhizodeposits or aboveground via leaf litter, with recent research pointing to a higher importance of the former for driving forest soil food webs. Using natural abundance stable isotopes of wheat (C3 plant) and maize (C4 plant), we followed and quantified the incorporation of shoot residue- and root-derived maize C into the soil animal food web of an arable field for 1 year, thereby disentangling the importance of shoot residue- versus root-derived resources for arable soil food webs. On average, shoot residue-derived resources only contributed less than 12% to soil arthropod body C, while incorporation of root derived resources averaged 26% after 2 months of maize crop and increased to 32% after 1 year. However, incorporation of root-derived maize C did not consistently increase with time: rather, it increased, decreased or remained constant depending on species. Further, preference of shoot residue- or root-derived resources was also species-specific with about half the species incorporating mainly root-derived C, while only a few species preferentially incorporated shoot residue-derived C, and about 40% incorporated both shoot residue- as well as root derived C. The results highlight the predominant importance of root-derived resources for arable soil food webs and suggest that shoot residues only form an additional resource of minor importance. Variation in the use of plant-derived C between soil arthropod species suggests that the flux of C through soil food webs of arable systems can only be disentangled by adopting a species-specific approach. PMID- 26267406 TI - Candida rugosa Lipase Immobilized onto Acid-Functionalized Multi-walled Carbon Nanotubes for Sustainable Production of Methyl Oleate. AB - The chemical production of methyl oleate using chemically synthesized fatty acid alcohols and other toxic chemicals may lead to significant environmental hazards to mankind. Being a highly valuable fatty acid replacement raw material in oleochemical industry, the mass production of methyl oleate via environmentally favorable processes is of concern. In this context, an alternative technique utilizing Candida rugosa lipase (CRL) physically adsorbed on multi-walled carbon nanotubes (MWCNTs) has been suggested. In this study, the acid-functionalized MWCNTs prepared using a mixture of HNO3 and H2SO4 (1:3 v/v) was used as support for immobilizing CRL onto MWCNTs (CRL-MWCNTs) as biocatalysts. Enzymatic esterification was performed and the efficiency of CRL-MWCNTs was evaluated against the free CRL under varying conditions, viz. temperature, molar ratio of acid/alcohol, solvent log P, and enzyme loading. The CRL-MWCNTs resulted in 30 110 % improvement in the production of methyl oleate over the free CRL. The CRL MWCNTs attained its highest yield (84.17 %) at 50 degrees C, molar ratio of acid/alcohol of 1:3, 3 mg/mL of enzyme loading, and iso-octane (log P 4.5) as solvent. Consequently, physical adsorption of CRL onto acid-functionalized MWCNTs has improved the activity and stability of CRL and hence provides an environmentally friendly means for the production of methyl oleate. PMID- 26267407 TI - Oxytocin enables novelty seeking and creative performance through upregulated approach: evidence and avenues for future research. AB - Oxytocin is an evolutionary ancient hypothalamic neuropeptide well known for its role in reproduction, social bonding, and group affiliation. Recent work has linked oxytocin in humans to creative cognition--the ability to produce insights, ideas, and problem solutions that are original and potentially useful. Here we review this literature, focusing on the relationship between (1) single nucleotide polymorphisms in the oxytocin receptor (OXTR) gene; endogenous oxytocin from blood plasma, and intranasal administration of oxytocin (vs placebo), and (2) creativity-related traits (e.g., novelty seeking, extraversion, and openness to experience), and behaviors (e.g., exploration, divergent thinking, original ideation, and problem solving). Findings are interpreted in the context of the dual pathway to creativity model and except for OXTR: (1) reveal a weak to moderate but consistent association between oxytocin and creativity, which emerges because (2) oxytocin enables the cognitive flexibility pathway more than persistent information processing. Findings can be best understood in terms of oxytocin's putative effects on dopaminergic activity and concomitant approach tendency. PMID- 26267408 TI - A diffusive ink transport model for lipid dip-pen nanolithography. AB - Despite diverse applications, phospholipid membrane stacks generated by dip-pen nanolithography (DPN) still lack a thorough and systematic characterization that elucidates the whole ink transport process from writing to surface spreading, with the aim of better controlling the resulting feature size and resolution. We report a quantitative analysis and modeling of the dependence of lipid DPN features (area, height and volume) on dwell time and relative humidity. The ink flow rate increases with humidity in agreement with meniscus size growth, determining the overall feature size. The observed time dependence indicates the existence of a balance between surface spreading and the ink flow rate that promotes differences in concentration at the meniscus/substrate interface. Feature shape is controlled by the substrate surface energy. The results are analyzed within a modified model for the ink transport of diffusive inks. At any humidity the dependence of the area spread on the dwell time shows two diffusion regimes: at short dwell times growth is controlled by meniscus diffusion while at long dwell times surface diffusion governs the process. The critical point for the switch of regime depends on the humidity. PMID- 26267409 TI - Controlled MoS2 layer etching using CF4 plasma. AB - A few-layered molybdenum disulfide (MoS2) thin film grown by plasma enhanced chemical vapor deposition was etched using a CF4 inductively coupled plasma, and the possibility of controlling the MoS2 layer thickness to a monolayer of MoS2 over a large area substrate was investigated. In addition, damage and contamination of the remaining MoS2 layer surface after etching and a possible method for film recovery was also investigated. The results from Raman spectroscopy and atomic force microscopy showed that one monolayer of MoS2 was etched by exposure to a CF4 plasma for 20 s after an initial incubation time of 20 s, i.e., the number of MoS2 layers could be controlled by exposure to the CF4 plasma for a certain processing time. However, XPS data showed that exposure to CF4 plasma induced a certain amount of damage and contamination by fluorine of the remaining MoS2 surface. After exposure to a H2S plasma for more than 10 min, the damage and fluorine contamination of the etched MoS2 surface could be effectively removed. PMID- 26267410 TI - Nonintuitive Diabatic Potential Energy Surfaces for Thioanisole. AB - Diabatization of potential energy surfaces is a technique that enables convenient molecular dynamics simulations of electronically nonadiabatic processes, but diabatization itself is nonunique and can be inconvenient; the best methods to achieve diabatization are still under study. Here, we present the diabatization of two electronic states of thioanisole in the S-CH3 bond stretching and C-C-S-C torsion two-dimensional nuclear coordinate space containing a conical intersection. We use two systematic methods: the (orbital-dependent) 4-fold way and the (orbital-free) Boys localization diabatization method. These very different methods yield strikingly similar diabatic potential energy surfaces that cross at geometries where the adiabatic surfaces are well separated and do not exhibit avoided crossings, and the contours of the diabatic gap and diabatic coupling are similar for the two methods. The validity of the diabatization is supported by comparing the nonadiabatic couplings calculated from the diabatic matrix elements to those calculated by direct differentiation of the adiabatic states. PMID- 26267411 TI - Biomimetic synthesis of Tramadol. AB - Tramadol has recently been isolated from the roots and bark of Nauclea latifolia. A plausible biosynthetic pathway has been proposed and the product-precursor relationship has been probed by (13)C position-specific isotope analysis. By further exploring this pathway, we demonstrate that a key step of the proposed pathway can be achieved using mild conditions that mimic in vivo catalysis. PMID- 26267412 TI - Survival benefit of anti-HER2 therapy after whole-brain radiotherapy in HER2 positive breast cancer patients with brain metastasis. AB - AIM: We aimed to assess the survival benefit of epidermal growth factor receptor 2 (HER2)-positive breast cancer patients with brain metastasis (BM) after whole brain radiotherapy (WBRT) in combination with systemic treatments, especially anti-HER2 therapy. METHODS: This retrospective study analyzed the overall survival (OS) of 60 HER2-positive breast cancer patients with BM after WBRT in combination with systemic treatments. Among them, 42 patients received chemotherapy while 18 patients did not receive after WBRT. With regard to anti HER2 therapy, after WBRT, 17 patients received anti-HER2 treatment without prior adjuvant trastuzumab-based therapy, 7 patients received anti-HER2 treatment with prior adjuvant trastuzumab-based therapy, and 36 patients did not receive further anti-HER2 treatment. All patients were followed up regularly until January 23, 2013. RESULTS: The median OS of patients with BM was 12 months. Patients who received anti-HER2 therapy and chemotherapy after WBRT had significantly better survival compared with patients who did not receive further treatment. Patients who received anti-HER2 treatment after WBRT but did not receive adjuvant trastuzumab-based therapy for early breast cancer had better OS, followed by patients who received anti-HER2 agent both in adjuvant treatment and after WBRT and patients who did not receive anti-HER2 treatment. Multivariate analysis showed that Karnofsky Performance Status, control of extracranial metastases, chemotherapy after WBRT, and anti-HER2 therapy combined with WBRT were all independent predictors for OS. CONCLUSION: Both chemotherapy and anti-HER2 therapy after WBRT could improve OS. Moreover, patients without prior exposure to adjuvant anti-HER2 treatment may have survival benefit superior to those of patients with prior exposure. PMID- 26267413 TI - [The Hypereosinophilic Syndromes in Childhood]. AB - The hypereosinophilic syndromes are rare disorders in childhood and require extensive differential diagnostic considerations. In the last years the earlier "idiopathic HES" called syndromes could be differentiated into molecular biologically, immunophenotypically and clinically more characterized heterogeneous diseases with high therapeutic and prognostic relevance. Nowadays the term HES summarizes diseases, which go hand in hand with a local or systemic hypereosinophilia (HE) connected with an organ damage. Depending on the cause of the HE one differentiates primary/neoplastic HES (HESN) from secondary/reactive HES (HESR). The latter develops reactively in connection with allergies, parasitosis, medications, neoplasia or a clonal increase of T-lymphocytes among others. With HESN the HE results from a clonal increase of eosinophilic granulocytes. While for some subgroups of the HESN (among others FIP1L1-PDGFRA fusion gene) the administration of a tyrosine kinase inhibitor is a new and effective therapy option, glucocorticoids still represent the medication of first choice for many not PDGFRA associated variants. Different immunomodulatory drugs or cytostatic agents are necessary to allow dose reduction of glucocorticoids. The promising therapy with anti-IL-5 antibodies is still not approved in infancy, could however become a treatment option in the future. Due to the present lack of knowledge about the HES in infancy the establishment of a register should be aimed for the treatment of HES in infancy. PMID- 26267414 TI - Effect of silica on porosity, strength, and toughness of pressureless sintered calcium phosphate-zirconia bioceramics. AB - The preparation of dense, high-strength calcium phosphate-zirconia (CaP-ZrO2) composed bioceramics is realized via versatile pressureless sintering by adding silica nanoparticles. Two different weight ratios of HAp:ZrO2, 9:1 and 1:1, are used with varying silica contents from 5 to 20 wt%. After sintering at 1200 degrees C, the phase composition, microstructure, porosity, biaxial bending strength, and fracture toughness as well as SBF in vitro bioactivity are characterized. We show that the addition of silica altered the crystal phase composition, inhibiting the formation of non-favourable cubic ZrO2. Furthermore, SiO2 addition leads to an increase of the biaxial bending strength, and the fracture toughness of CaP-ZrO2-containing materials. With the addition of 20 wt% silica we find the highest characteristic strength (268 MPa) and toughness (2.3 +/- 0.1 MPam(0.5)) at <1% porosity. Both mechanical properties are 2 times higher than those of pure hydroxyapatite. At the same time we observe for the very same composition similar bioactivity to that of pure hydroxyapatite. PMID- 26267415 TI - Protective effect of vagotomy suggests source organ for Parkinson disease. PMID- 26267416 TI - Lower Brain-Derived Neurotropic Factor Levels in Untreated Adolescents With First Episode Psychosis. AB - OBJECTIVE: Brain-derived neurotropic factor (BDNF) is known to play a role in the pathogenesis of schizophrenia. However, the relationship between early onset schizophrenia and BDNF has not been extensively studied. The aim of the study was to compare the levels of BDNF between adolescent patients with first-episode psychosis (FEP) and the healthy control subjects. METHOD: The study was conducted in the Department of Child Psychiatry at Dicle University. A total of 26 adolescent patients aged between 11 and 17 years who had not received previous therapy and whose conditions were diagnosed with psychosis according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and 26 age and sex-matched healthy adolescent control subjects were included. Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime version, and the Positive and Negative Symptom Scale were conducted with all participants. The clinical global impression was used to evaluate disease severity. The BDNF levels were measured in the serum by enzyme-linked immunosorbent assay method. RESULTS: The mean (SD) age was 14.6 (1.6) years in both FEP group (male/female, 11/15) and the control group (P > 0.05). The FEP group had significantly lower serum BDNF levels (2.0 +/- 1.9 ng/mL) compared with the control group (3.4 +/- 3.0 ng/mL, P = 0.03). There was no significant relationship between BDNF concentration and the Positive and Negative Symptom Scale (positive and negative scores) scores (r = -0.14, P = 0.74 and r = 0.49, P = 0.22, respectively). There was no significant relationship between the duration of untreated psychosis and serum BDNF levels (r = -0.22, P = 0.32). CONCLUSIONS: High incidence of schizophrenia in patients with FEP suggests a relationship between BDNF levels and the pathogenesis of schizophrenia. We suggest that BDNF may be a useful neurobiological marker of early onset schizophrenia. PMID- 26267417 TI - Exploring Genetic Variability at PI, GSK3, HPA, and Glutamatergic Pathways in Lithium Response: Association With IMPA2, INPP1, and GSK3B Genes. AB - Lithium is considered the first-line treatment in bipolar disorder, although response could range from an excellent response to a complete lack of response. Response to lithium is a complex phenotype in which different factors, part of them genetics, are involved. In this sense, the aim of this study was to investigate the potential association of genetic variability at genes related to phosphoinositide, glycogen synthetase kinase-3 (GSK3), hypothalamic-pituitary adrenal, and glutamatergic pathways with lithium response. A sample of 131 bipolar patients (99 type I, 32 type II) were grouped and compared according to their level of response: excellent responders (ER), partial responders (PR), and nonresponders (NR). Genotype and allele distributions of the rs669838 (IMPA2), rs909270 (INNP1), rs11921360 (GSK3B), and rs28522620 (GRIK2) polymorphisms significantly differed between ER, PR, and NR. When we compared the ER versus PR+NR, the logistic regression showed significant association for rs669838-C (IMPA2; P = 0.021), rs909270-G (INPP1; P = 0.009), and rs11921360-A (GSK3B; P = 0.004) with lithium nonresponse. Haplotype analysis showed significant association for the haplotypes rs3791809-rs4853694-rs909270 (INPP1) and rs1732170 rs11921360-rs334558 (GSK3B) and lithium response. Our study is in line with previous studies reporting association between genetic variability at these genes and lithium response, pointing to an effect of IMPA2, INPP1, and GSK3B genes to lithium response in bipolar disorder patients. Further studies with larger samples are warranted to assess the strength of the reported associations. PMID- 26267418 TI - Antidepressants in Type II Versus Type I Bipolar Depression: A Randomized Discontinuation Trial. AB - BACKGROUND: We sought to test the hypothesis that antidepressants (ADs) may show preferential efficacy and safety among patients with type II bipolar disorder (BD, BD-II) more than patients with type I BD (BD-I). METHODS: Patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, BD-I (n = 21) and BD-II (n = 49) in acute major depressive episodes were treated with ADs plus mood stabilizers to euthymia sustained for 2 months and then randomized openly to continue or discontinue ADs for up to 3 years. Outcomes were episode recurrences and changes in standardized symptom ratings. RESULTS: In follow-up averaging 1.64 years, both subgroups showed improvement in depressive episode frequency with AD continuation, but contrary to the hypothesis, more improvement was seen in BD-I than in BD-II (for type II, mean [standard deviation] decrease in depressive episodes per year, 0.21 [0.26]; for type I, mean (SD) decrease, 0.35 [0.15]). Subjects with BD-II who continued on ADs had slightly more depressive, but fewer manic/hypomanic, episodes than subjects with BD-I. No notable differences were seen in either group in time to a recurrence of mood episodes or total time-in-remission. CONCLUSIONS: The findings do not confirm the hypothesis that long-term AD treatment in patients with BP-II has better outcomes than in patients with BD-I, except somewhat lower risk of manic/hypomanic episodes. PMID- 26267419 TI - Effectiveness and Predictors of Continuation of Paliperidone Palmitate Long Acting Injection Treatment: A 12-Month Naturalistic Cohort Study. AB - Antipsychotic long-acting injectable (LAI) medication has an important place as a treatment option in schizophrenia with evolving evidence to support clinical benefit over oral medication. Paliperidone palmitate is recently licensed as an LAI. We studied a naturalistic cohort of all identifiable patients who initiated paliperidone LAI in a specific United Kingdom region (Sussex) from first availability up to January 2013 (n = 179). Favorably, 60% of the cohort continued paliperidone LAI beyond 12 months from initiation. Schizophrenia diagnosis was significantly associated with 12-month continuation on univariate analysis (65% continuation rate at 12 months in this diagnostic subgroup). No baseline variables were identified as independently associated with 12-month continuation. However, fewer inpatient days after initiation (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.003-1.011; P = 0.002), dose adjustment up or down (OR, 3.46; 95% CI, 1.26-9.51; P = 0.016), and a higher maintenance dose (OR, 8.31; 95% CI, 1.84-37.51; P = 0.006) during treatment course were all independently associated with continuation on multivariate analysis. Our findings support the importance of a collaborative approach with the LAI recipient in treatment decision making to enhance treatment effectiveness. PMID- 26267420 TI - The Effect of Clozapine on Hematological Indices: A 1-Year Follow-Up Study. AB - Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and is linked to a need for mandatory hematological monitoring. Besides agranulocytosis, other hematological aberrations have resulted in premature termination in some cases. Considering clozapine's role in immunomodulation, we proceeded to investigate the impact of clozapine on the following 3 main hematological cell lines: red blood cells, platelets, white blood cells (WBCs), and its differential counts. Data were extracted from patients initiated on clozapine between January 2009 and December 2010 at a single hospital. Patients with a preclozapine complete blood count, who were receiving clozapine during the 1-year follow-up period, were included in the present investigation. Counts of red blood cells, platelets, WBC, and its differential including neutrophils, lymphocytes, monocytes, eosinophils, and basophils were extracted and trajectories plotted. One hundred one patients were included in this study and 66 remained on clozapine at the end of 1 year. There was a synchronized but transient increase in WBC, neutrophils, monocytes, eosinophils, basophils, and platelets beginning as early as the first week of clozapine treatment. There were no cases of agranulocytosis reported in this sample, and five developed neutropenia. A spike in neutrophils immediately preceded the onset of neutropenia in three of the five. The cumulative incidence rates were 48.9% for neutrophilia, 5.9% for eosinophilia, and 3% each for thrombocytosis and thrombocytopenia. Early hematological aberrations are visible across a range of cell lines, primarily of the myeloid lineage. These disturbances are transient and are probably related to clozapine's immunomodulatory properties. We do not suggest discontinuing clozapine as a consequence of the observed aberrations. PMID- 26267421 TI - Remission Rate and Functional Outcomes During a 6-Month Treatment With Osmotic Release Oral-System Methylphenidate in Children With Attention Deficit/Hyperactivity Disorder. AB - Many definitions have been used to evaluate remission in patients with attention deficit/hyperactivity disorder (ADHD) in different studies resulting with varied remission rates. This open-label, multicenter study investigated the remission rate in Chinese children (n = 239; aged 6-16 years) with a diagnosis of ADHD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), treated with osmotic-release oral-system methylphenidate at doses of 18, 36, and 54 mg, once daily. Two definitions of remission were used: (1) (primary end point): average scores of SNAP-IV (Swanson, Nolan, and Pelham, Fourth Edition) items of 1 or less (0-3 rating scale for each item) according to the subtype of ADHD (inattentive [1-9], hyperactive-impulsive [10-18], and combined type [1-18]), and (2) total score of SNAP-IV items 1 to 18 of 18 or less, at week 8. The study consisted of screening/baseline, titration/open-label treatment (8 weeks), and extended observation (up to 24 weeks) phases. Secondary efficacy assessments were Clinical Global Impression-Improvement (clinical efficacy), Behavior Rating Inventory of Executive Function Scale (BRIEF; executive function behaviors), and Weiss Functional Impairment Rating Scale (social function). Validity of remission was assessed by comparing the function measures (BRIEF and Weiss's) between patients who achieved remission and those who did not. At week 8, 69.3% (151/218) of patients achieved remission by definition 1, and 73.2% (161/220) by definition 2. At weeks 8 and 24, the remission group had significantly lower BRIEF, Weiss's, and Clinical Global Impression-Improvement scores (P < 0.001 for all) compared with the nonremission group. Overall, treatment with osmotic-release oral-system methylphenidate was well tolerated, with increased remission rates in children with ADHD. PMID- 26267422 TI - A retrospective classification of diagnoses in terms of DSM-5 for patients included in randomized controlled trials of Ginkgo biloba extract EGb 761((r)). AB - When the early trials of Ginkgo biloba extract EGb 761((r)) were conducted, different terms were used to denote ageing-associated neurocognitive disorders. With the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), a taxonomy covering dementia and pre-dementia stages of such disorders became available. DSM-5 diagnostic criteria for neurocognitive disorders (NCDs) were applied to patients with any type of ageing-associated cognitive impairment, including dementia, enrolled in randomized controlled clinical trials of EGb 761((r)), taking into account the reported inclusion and exclusion criteria and patient characteristics at baseline. For 23 of 31 trials (74 %), the inclusion diagnoses could be classified as NCD in accordance with DSM 5. Thirteen trials enrolled patients with major NCD, four trials enrolled patients with mild NCD and six trials enrolled patients with NCD, who could not be classified unambiguously as having mild or major NCD. Although various terms were formerly used for neurocognitive disorders, the patients enrolled in the majority of clinical trials with EGb 761((r)) could be classified retrospectively using modern DSM-5 diagnostic criteria. PMID- 26267423 TI - Clinical Effectiveness of Moisturizers in Atopic Dermatitis and Related Disorders: A Systematic Review. AB - BACKGROUND: Moisturizers are widely used for atopic dermatitis (AD) and related conditions, but available evidence of their effectiveness has not been reviewed in a systematic fashion. OBJECTIVES: Our objective was to investigate the effectiveness of emollients, as a group and individually, in the treatment of AD and related conditions, by means of a systematic review. DATA SOURCES: Studies indexed in MEDLINE and/or Embase before 16 January 2015. STUDY ELIGIBILITY CRITERIA: Controlled clinical studies comparing the clinical effect of a moisturizer against its vehicle, another moisturizer, or no treatment were eligible. For the outcomes transepidermal water loss (TEWL) and stratum corneum hydration, uncontrolled before-after designs were also eligible. PARTICIPANTS: Participants were patients with AD, irritant hand dermatitis, and/or ichthyosis vulgaris. RESULTS: Out of the 595 publications initially identified, 45 (48 studies, 3262 patients) were eligible for inclusion. A vast majority of studies indicate that moisturizers have beneficial effects on clinical symptoms [SCORAD (SCORing Atopic Dermatitis) reductions ranging from 0 to 2.7 points], TEWL (range 0 to -12.2 g/m(2)h) and stratum corneum hydration (range +8 to +100%). Direct comparisons between individual moisturizers are still scarce, but the clinical effect appears to be much more well-documented for urea and glycerin than, for example, propylene glycol, lactate, ceramide, and aluminum chlorohydrate. Compared with urea studies, glycerin studies were more often associated with a high risk of bias. LIMITATIONS: Due to differences in study designs and outcome measures, a quantitative meta-analytic approach was not deemed feasible, and formal indicators of publication bias such as funnel plots could not be used. However, a large number of moderately sized studies with positive outcomes could be compatible with selective publishing of favourable results. CONCLUSIONS: The clinical effect of moisturizers is well-documented. Urea-based preparations may be preferable as a first-line treatment, but there is an unmet need for well powered comparisons between individual moisturizers. PMID- 26267424 TI - Quality of Life and Gastrointestinal Symptoms in Long-Term Treated Dermatitis Herpetiformis Patients: A Cross-Sectional Study in Finland. AB - BACKGROUND: Dermatitis herpetiformis (DH) is a cutaneous manifestation of celiac disease. Both conditions are treated with a restrictive life-long gluten-free diet (GFD). Treated celiac disease patients have been shown to have more severe gastrointestinal symptoms and inferior quality of life compared with healthy controls, but evidence regarding quality of life in DH is lacking. OBJECTIVE: The aim was to evaluate whether long-term GFD-treated DH patients suffer from persistent gastrointestinal symptoms and if they experience a drawdown in quality of life. METHODS: Gastrointestinal symptoms and quality of life were assessed in 78 long-term GFD-treated DH patients using the validated Gastrointestinal Symptom Rating Scale, Psychological General Well-Being and Short Form 36 Health Survey questionnaires. The findings were compared with 110 healthy controls, population based reference values and 371 treated celiac disease controls. RESULTS: The median age of the DH patients at the time of the study was 57 years, and 51 % were male. Significant differences in gastrointestinal symptoms or quality of life were not detected when treated DH patients were compared with healthy controls, but treated DH patients had less severe gastrointestinal symptoms and increased quality of life compared with celiac disease controls. Female DH patients had more severe gastrointestinal symptoms and reduced vitality compared with male DH patients. The presence of skin symptoms and the adherence to or duration of GFD did not have any influence on gastrointestinal symptoms or quality of life. CONCLUSION: We conclude that long-term GFD-treated DH patients do not suffer from the burden of dietary treatment and have a quality of life comparable to that of controls. PMID- 26267425 TI - Influence of increasing construct constraint in the presence of posterolateral deficiency at knee replacement: A biomechanical study. AB - When faced with posterolateral corner (PLC) deficiency, surgeons must choose a total knee replacement (TKR) construct that provides the appropriate level of constraint. This should match the internal constraint of the device to the soft tissue host laxity pattern. Little guidance is available peroperatively, with factors influencing final component choice remaining ill defined. This study aimed to quantify the effect of PLC insufficiency on the "envelope of laxity" (EoL) after TKR and the effect of increasingly component constraint upon knee behavior through a functional arc of flexion. Using computer navigation, mixed effect modeling and loaded cadaveric legs--laxity was quantified under separate states: the native knee, after implantation of a posterior stabilized (PS)-TKR, after sectioning the lateral (fibular) collateral ligament and popliteus tendon (PS-TKR-PLC), and after re-implantation with a semi-constrained "total stabilized" knee replacement (TS-TKR). Laxity was quantified from 0 to 110 degrees of flexion for anterior draw, varus-valgus, and internal-external rotation. Implantation of the PS-TKR was consistently associated with increased constraint when compared to the native knee. PLC sectioning led to significantly increased laxity during varus stress from mid to deep flexion. Revision to a TS TKR construct restored constraint mimicking that of the primary state but only for the arc of motion 0-90 degrees . In a posterolateral deficient state, a fixed bearing semi-constrained TS-TKR restored the knee to near normal kinematics but this was only achieved from an arc of motion 0-90 degrees of flexion. At higher flexion angles, there remained an unfavorable laxity pattern with varus stress opening. PMID- 26267426 TI - The equal effectiveness of different defensive strategies. AB - Plants have evolved a variety of defensive strategies to resist herbivory, but at the interspecific level, the relative effectiveness of these strategies has been poorly evaluated. In this study, we compared the level of herbivory between species that depend on ants as indirect defenders and species that rely primarily on their own direct defenses. Using a dataset of 871 species and 1,405 data points, we found that in general, ant-associated species had levels of herbivory equal to those of species that are unattractive to ants; the pattern was unaffected by plant life form, climate and phylogenetic relationships between species. Interestingly, species that offer both food and nesting spaces for ants suffered significantly lower herbivory compared to species that offer either food or nesting spaces only or no reward for ants. A negative relationship between herbivory and latitude was detected, but the pattern can be changed by ants. These findings suggest that, at the interspecific level, the effectiveness of different defensive strategies may be equal. Considering the effects of herbivory on plant performance and fitness, the equal effectiveness of different defensive strategies may play an important role in the coexistence of various species at the community scale. PMID- 26267427 TI - Improving access and timeliness of care for veterans with head and neck squamous cell carcinoma: A multidisciplinary team's approach. AB - OBJECTIVES/HYPOTHESIS: With the prevalence of head and neck squamous cell carcinoma (HNSCC) nearly twice as high in veterans (6%) than general populations (3%), the noted problems of long waits and access to care in United States Veterans Affairs (VA) hospitals across the country are pressing. We examined primary outcome measures of timeliness and access to care for our patients with HNSCC assessing a multidisciplinary team approach at our VA hospital. STUDY DESIGN: Retrospective chart review. METHODS: Our patients newly diagnosed with HNSCC were identified from two 24-month periods: diagnosis before (group 1, 2005 2006) and after (group 2, 2008-2009) implementing our multidisciplinary team in 2007. No significant differences in age (P = .13) or disease stage (P = .18) occurred between groups. Primary and secondary outcomes (i.e., treatment modality, imaging, completion of treatment, survival) were compared. RESULTS: Timeliness to care improved for all measures. Improvement was significant for times from consult placed to seen in clinic (27.5-16.5 days; P < 0.0001) and from positive biopsy reported to date of initiating definitive treatment (35-27 days; P = 0.04). Pretreatment consults to various services represented by the multidisciplinary team increased from one to four (P < 0.0001). Two-year mortality was approximately the same between group 1 (33%) and group 2 (36%) (P = 0.035). Five-year mortality was slightly better in group 2 (50%) versus group 1 (61%), although not statistically significant. CONCLUSION: Our veteran population with HNSCC had improved timeliness and access to care with our multidisciplinary approach. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:627-631, 2016. PMID- 26267428 TI - Methane oxidation in a biofilter (Part 2): A lab-scale experiment for model calibration. AB - In this study an experimental study on a biological methane oxidation column presented with the aim to calibrate a mathematical model developed in an earlier study. The column was designed to reproduce at lab-scale a real biofilter trying to consider the more probable landfill boundary conditions. Although the methane oxidation efficiency in the column was lower than the expected (around 35%), an appropriate model implementation showed an acceptable agreement between the outcomes data of the model simulation and the experimental data (with Theil's Inequality Coefficient value of 0.08). A calibrated model allows a better management of the biofilter performance in terms of methane oxidation. PMID- 26267429 TI - Litter quality indirectly influences community composition, reproductive mode and trophic structure of oribatid mite communities: a microcosm experiment. AB - Our knowledge of the assembly processes of species-rich oribatid mite communities is fairly limited. Also, very little information is available on the effects of habitat factors on these processes. In this paper, the role of litter quality in pattern formation was investigated in a microcosm experiment using the "home field advantage" approach. Native (home) and foreign (away) types of microarthropod assemblages were extracted from three types of litter samples (Turkey oak, Scots pine and black locust tree), and transferred alive into 'home' and 'away' samples, which have been defaunated and reinoculated with microorganisms to form microcosms. Microarthropods were extracted from the microcosms after incubation for 3-12 months. In addition to species identification and abundance records, some chemical properties of the litter were measured. We hypothesized that oribatid mite communities deteriorate, the proportion of parthenogenetic individuals decreases and the proportion of omnivorous individuals increases in 'away' microcosms in contrast to 'home' systems. Pine and oak litter were favourable for all the three types of oribatid communities since their community traits in these types of litter were found to be similar to 'home' litter. Black locust litter was favourable only for its native oribatid community in the long run. The proportion of parthenogenetic individuals partly supported our hypothesis, mainly in black locust litter. The relative abundance of omnivorous individuals did not differ significantly between treatments. Litter quality is likely to influence oribatid mite assemblages only indirectly. PMID- 26267430 TI - Influenza vaccine effectiveness in the tropics: moderate protection in a case test-negative analysis of a hospital-based surveillance population in Bangkok between August 2009 and January 2013. AB - Influenza in the tropics occurs year round with peaks that correspond variably to temperate regions. However, data on influenza vaccine effectiveness (VE) in the tropics is sparse. We report on the effectiveness of influenza vaccine to prevent medically attended laboratory confirmed influenza from sentinel surveillance conducted at a Thai military medical facility in Bangkok, Thailand from August 2009 to January 2013. Patients >=6 months old presenting with influenza-like illness underwent combined nasal/throat swabs which were tested by influenza RT PCR. A case test-negative study design was used to evaluate VE. Of 2999 samples available for analysis,1059 (35.3%) were PCR-positive (cases) and 1940 (64.6%) were PCR-negative (test-negative controls). Five hundred and seven (16.9%) of these patients reported being vaccinated within the previous 12 months. Periods of high and low influenza activity were defined based on publicly available Thai Ministry of Public Health data. Overall VE adjusted for age and epiweek was found to be 50.1% (95%CI: 35.0, 61.9%). The May to April adjusted VE for year 2010, 2011 and 2012 was 57.7% (95%CI: 33.7, 73.8%), 57.1% (95% CI: 35.2, 68.3%) and 37.6% (95% CI: 3.5, 62.9%).During high influenza activity in years with the same vaccine formulation, the adjusted VE was 54.9% (95%CI: 38.9, 66.9%). VE appeared to be much higher during high versus low influenza activity periods. The adjusted point estimate for VE was highest in the 18-49 year age group (76.6%) followed by 6-23 months (58.1%) and 2-17 years (52.5%). Adjusted estimates were not done for those >=50 years of age due to small numbers. VE in patients with underlying disease was 75.5% compared to 48.0% in those without. Our findings demonstrate moderate protection by influenza vaccination and support the utility of influenza vaccination in the tropics including in very young children and those with underlying disease. PMID- 26267431 TI - Methotrexate ultraviolet reactivation reaction in the setting of voriconazole induced phototoxicity. PMID- 26267433 TI - Connecting evolution, medicine, and public health. PMID- 26267432 TI - Dipeptidyl peptidase 4 promotes epithelial cell transformation and breast tumourigenesis via induction of PIN1 gene expression. AB - BACKGROUND AND PURPOSE: Dipeptidyl peptidase 4 (DPP4) is an aminopeptidase that is widely expressed in different cell types. Recent studies suggested that DPP4 plays an important role in tumour progression in several human malignancies. Here we have examined the mechanisms by which up-regulation of DPP4 expression causes epithelial transformation and mammary tumourigenesis. EXPERIMENTAL APPROACH: Expression of DPP4 and the peptidylprolyl cis/trans isomerase, NIMA-interacting 1 (PIN1), and the cytotoxic effects of combined treatment with sitagliptin and juglone were investigated by immunohistochemistry, immunoblotting, real-time PCR, TUNEL and soft agar assays, using MCF7 cells. The effects of sitagliptin on tumour development in vivo were studied in the syngeneic 4T1 metastatic breast cancer model. KEY RESULTS: Activity of the transcription factor E2F1 induced by EGF was enhanced by DPP4, thus increasing PIN1 expression. Furthermore, DPP4 enhanced MEK/ERK and JNK/c-Jun signalling induced by EGF, inducing AP-1 activity and epithelial cell transformation. In contrast, DPP4 silencing or DPP4 inhibition in MCF7 cells inhibited PIN1 expression via E2F1 activity induced by EGF, decreasing colony formation and inducing DNA fragmentation. In the syngeneic 4T1 metastatic breast cancer model, DPP4 overexpression increased tumour development, whereas treatment with sitagliptin and/or juglone suppressed it. Consistent with these observations, DPP4 levels were positively correlated with PIN1 expression in human breast cancer. CONCLUSIONS AND IMPLICATIONS: DPP4 promoted EGF-induced epithelial cell transformation and mammary tumourigenesis via induction of PIN1 expression, suggesting that sitagliptin targeting of DPP4 could be a treatment strategy in patients with breast cancer. PMID- 26267434 TI - How are we made?: Even well-controlled experiments show the complexity of our traits. PMID- 26267436 TI - Rethinking the dispersal of Homo sapiens out of Africa. AB - Current fossil, genetic, and archeological data indicate that Homo sapiens originated in Africa in the late Middle Pleistocene. By the end of the Late Pleistocene, our species was distributed across every continent except Antarctica, setting the foundations for the subsequent demographic and cultural changes of the Holocene. The intervening processes remain intensely debated and a key theme in hominin evolutionary studies. We review archeological, fossil, environmental, and genetic data to evaluate the current state of knowledge on the dispersal of Homo sapiens out of Africa. The emerging picture of the dispersal process suggests dynamic behavioral variability, complex interactions between populations, and an intricate genetic and cultural legacy. This evolutionary and historical complexity challenges simple narratives and suggests that hybrid models and the testing of explicit hypotheses are required to understand the expansion of Homo sapiens into Eurasia. PMID- 26267438 TI - Crystal Structure Analysis of La2Ni6CoD(x) During Deuterium Absorption Process. AB - The crystal structures of La2Ni6CoD(x) (x = 5.2 and 9.6) were determined by in situ neutron diffraction along the P-C isotherm. La2Ni6CoD(5.2) (phase I) was found to be orthorhombic with lattice parameters a = 0.500670(2) nm, b = 0.867211(4) nm, and c = 2.99569(7) nm. The 10 deuterium sites were located in the MgZn2-type and CaCu5-type cells, with deuterium contents of 0.95 D/M and 0.39 D/M, respectively. The full deuteride La2Ni6CoD(9.6) (phase II) was monoclinic with lattice parameters a = 0.516407(3) nm, b = 0.894496(6) nm, c = 3.11206(1) nm, and beta = 90.15(1) degrees . The phase II had 11 sites for deuterium occupation. The deuterium contents of the MgZn2-type and the CaCu5-type cell were 1.63 D/M and 0.78 D/M, respectively. The sequence of phase transformation of La2Ni6Co was hexagonal, followed by orthorhombic (phase I), and then monoclinic (phase II), for the first absorption process. The phase transformation resulted in lowered symmetry and the variation of deuterium atom occupation. PMID- 26267435 TI - Led by the nose: Olfaction in primate feeding ecology. AB - Olfaction, the sense of smell, was a latecomer to the systematic investigation of primate sensory ecology after long years in which it was considered to be of minor importance. This view shifted with the growing understanding of its role in social behavior and the accumulation of physiological studies demonstrating that the olfactory abilities of some primates are on a par with those of olfactory dependent mammals such as dogs and rodents. Recent years have seen a proliferation of physiological, behavioral, anatomical, and genetic investigations of primate olfaction. These investigations have begun to shed light on the importance of olfaction in the process of food acquisition. However, integration of these works has been limited. It is therefore still difficult to pinpoint large-scale evolutionary scenarios, namely the functions that the sense of smell fulfills in primates' feeding ecology and the ecological niches that favor heavier reliance on olfaction. Here, we review available behavioral and physiological studies of primates in the field or captivity and try to elucidate how and when the sense of smell can help them acquire food. PMID- 26267439 TI - Developmental Trajectories of Social Skills during Early Childhood and Links to Parenting Practices in a Japanese Sample. AB - This study used data from a nationwide survey in Japan to model the developmental course of social skills during early childhood. The goals of this study were to identify longitudinal profiles of social skills between 2 and 5 years of age using a group-based trajectory approach, and to investigate whether and to what extent parenting practices at 2 years of age predicted developmental trajectories of social skills during the preschool period. A relatively large sample of boys and girls (N > 1,000) was assessed on three social skill dimensions (Cooperation, Self-control, and Assertion) at four time points (ages 2, 3, 4, and 5), and on four parenting practices (cognitive and emotional involvement, avoidance of restriction and punishment, social stimulation, and social support for parenting) at age 2. The results indicated that for each social skill dimension, group-based trajectory models identified three distinct trajectories: low, moderate, and high. Multinomial regression analysis revealed that parenting practice variables showed differential contributions to development of child social skills. Specifically, Cooperation and Assertion were promoted by cognitive and emotional involvement, Self-control by social stimulation, and Assertion by avoidance of restriction and punishment. Abundant social support for parenting was not associated with higher child social skills trajectories. We found heterogeneity in developmental profiles of social skills during the preschool ages, and we identified parenting practices that contributed to different patterns of social skills development. We discussed the implications of higher-quality parenting practices on the improvement of child social skills across early childhood. PMID- 26267440 TI - Lung Cancer Resection at Hospitals With High vs Low Mortality Rates. AB - IMPORTANCE: Wide variations in mortality rates exist across hospitals following lung cancer resection; however, the factors underlying these differences remain unclear. OBJECTIVE: To evaluate perioperative outcomes in patients who underwent lung cancer resection at hospitals with very high and very low mortality rates (high-mortality hospitals [HMHs] and low-mortality hospitals [LMHs]) to better understand the factors related to differences in mortality rates after lung cancer resection. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective cohort study, 1279 hospitals that were accredited by the Commission on Cancer were ranked on a composite measure of risk-adjusted mortality following major cancer resections performed from January 1, 2005, through December 31, 2006. We collected data from January 1, 2006, through December 31, 2007, on 645 lung resections in 18 LMHs and 25 HMHs. After adjusting for patient characteristics, we used hierarchical logistic regression to examine differences in the incidence of complications and "failure-to-rescue" rates (defined as death following a complication). MAIN OUTCOMES AND MEASURES: Rates of adherence to processes of care, incidence of complications, and failure to rescue following complications. RESULTS: Among 645 patients who received lung resections (441 in LMHs and 204 in HMHs), the overall unadjusted mortality rates were 1.6% (n = 7) vs 10.8% (n = 22; P < .001) for LMHs and HMHs, respectively. Following risk adjustment, the difference in mortality rates was attenuated (1.8% vs 8.1%; P < .001) but remained significant. Overall, complication rates were higher in HMHs (23.3% vs 15.6%; adjusted odds ratio [aOR], 1.79; 95% CI, 0.99-3.21), but this difference was not significant. The likelihood of any surgical (aOR, 0.73; 95% CI, 0.26 2.00) or cardiopulmonary (aOR, 1.23; 95% CI, 0.70-2.16) complications was similar between LMHs and HMHs. However, failure-to-rescue rates were significantly higher in HMHs (25.9% vs 8.7%; aOR, 6.55; 95% CI, 1.44-29.88). CONCLUSIONS AND RELEVANCE: Failure-to-rescue rates are higher at HMHs, which may explain the large differences between hospitals in mortality rates following lung cancer resection. This finding emphasizes the need for better understanding of the factors related to complications and their subsequent management. PMID- 26267441 TI - Sustaining Our Nation's Seniors through Federal Food and Nutrition Programs. AB - Food insecurity is a pressing issue in the United States where one in six people suffer from hunger. The older adult population faces unique challenges to receiving adequate nutrition. The federal government currently employs four food and nutrition programs that target the senior population in an effort to address their specific needs. These are the Congregate Meals and Home Delivered Meals Programs (provided through the Older Americans Act), and the Senior Farmers' Market Nutrition Program and Child and Adult Care Food Program (provided by the United States Department of Agriculture). As the older adult population continues to grow, it will be important to evaluate and improve these programs and the social policies related to them. This manuscript describes each policy in depth, considers economic and political elements that have shaped each policy, describes the level of program success, and offers suggestions for future research and program development. PMID- 26267442 TI - A Descriptive Study of the Fluid Intake, Hydration, and Health Status of Rehabilitation Inpatients without Dysphagia Following Stroke. AB - Adequate hydration is important for all people, particularly when hospitalized with illness. Individuals with dysphagia following stroke are considered to be at risk of inadequate fluid intake and, therefore, dehydration, but there is little information about the fluid intake or hydration of individuals without dysphagia poststroke. This cohort study measured the average beverage intake, calculated the urea/creatinine ratio as a measure of hydration, and documented specific health outcomes of 86 people without dysphagia poststroke who were inpatients in rehabilitation centers. Participants drank on average 1504 ml per day (SD 359 ml), which typically represented 67% of their estimated daily requirement. Approximately 44% of the participants in the sample were dehydrated based on a blood urea nitrogen/creatinine ratio >20:1. Sixteen percent of participants were diagnosed with one or more of the health outcomes of dehydration/hypernatremia, urinary tract infection, or constipation. A greater level of dependence was associated with poorer beverage intake and higher risk of an adverse health outcome. Those in the older/elderly age range (particularly older women) and those with poor mobility were most at risk of poor hydration. This study highlights that patients in rehabilitation facilities poststroke, even without dysphagia, may be at risk of suboptimal fluid intake and hydration. PMID- 26267443 TI - Dietary Protein and Vitamin D Intake and Risk of Falls: A Secondary Analysis of Postmenopausal Women from the Study of Osteoporotic Fractures. AB - More than 90% of hip fractures in older Americans result from a fall. Inadequate intake of dietary protein and vitamin D are common in older adults, and diets in low these could contribute to loss of muscle mass and strength or coordination, in turn increasing the risk of falling. The objective of the study was to evaluate the relationship between protein and vitamin D intake with the occurrence of falls in older women in the Study of Osteoporotic Fracture, a prospective cohort of more than 4000 postmenopausal women participating from January 1997 to September 1998. Incident falls were ascertained for one year. Protein and vitamin D intake was assessed by a food frequency questionnaire; associations with a reported fall were estimated with logistic regression, adjusted for fall-related covariates and energy. Protein and vitamin D were modeled separately because of high correlation (rho = 0.55, P < 0.001). A total of 1429 women reported a fall within one year. In separate, unadjusted models dietary protein (per 1 g/kg increase) and vitamin D (per 100 International Unit (IU) increase) significantly increased the odds ratio (OR) of falling (OR 1.35 95% CI 1.15-1.59, OR 1.11 95% CI 1.03-1.19, respectively). Once fall-related covariates were added to each model, dietary protein and vitamin D were noncontributory to falls. While we could find no direct association between vitamin D and protein intake and fall prevention, adequate intake of these two nutrients are critical for musculoskeletal health in older adults. PMID- 26267444 TI - Food Insecurity and Health Outcomes Among Older Adults: The Role of Cost-Related Medication Underuse. AB - The purpose of this study is to examine the relationship between food security and cost-related medication underuse among older adults (persons aged 65 years and older) in the United States; and to determine if this relationship differs by sex, chronic disease status, and type of health insurance. Data are from a combined sample of older adults in the 2011 and 2012 National Health Interview Survey (N = 10,401). Both bivariate and multivariate analyses show a dose response relationship between food insecurity and cost-related medication underuse among the elderly--increasing likelihood of cost-related medication underuse with increasing severity of food insecurity (P < 0.001). This association is not conditional on sex, chronic disease status, or type of health insurance. However, females and those with a chronic condition are more likely to report cost-related medication underuse than males and those without a chronic condition respectively; and older adults with Medicare and Medicaid or other public insurance are less likely to report cost-related medication underuse than older adults with only Medicare. PMID- 26267445 TI - Distilling a Visual Network of Retinitis Pigmentosa Gene-Protein Interactions to Uncover New Disease Candidates. AB - BACKGROUND: Retinitis pigmentosa (RP) is a highly heterogeneous genetic visual disorder with more than 70 known causative genes, some of them shared with other non-syndromic retinal dystrophies (e.g. Leber congenital amaurosis, LCA). The identification of RP genes has increased steadily during the last decade, and the 30% of the cases that still remain unassigned will soon decrease after the advent of exome/genome sequencing. A considerable amount of genetic and functional data on single RD genes and mutations has been gathered, but a comprehensive view of the RP genes and their interacting partners is still very fragmentary. This is the main gap that needs to be filled in order to understand how mutations relate to progressive blinding disorders and devise effective therapies. METHODOLOGY: We have built an RP-specific network (RPGeNet) by merging data from different sources: high-throughput data from BioGRID and STRING databases, manually curated data for interactions retrieved from iHOP, as well as interactions filtered out by syntactical parsing from up-to-date abstracts and full-text papers related to the RP research field. The paths emerging when known RP genes were used as baits over the whole interactome have been analysed, and the minimal number of connections among the RP genes and their close neighbors were distilled in order to simplify the search space. CONCLUSIONS: In contrast to the analysis of single isolated genes, finding the networks linking disease genes renders powerful etiopathological insights. We here provide an interactive interface, RPGeNet, for the molecular biologist to explore the network centered on the non-syndromic and syndromic RP and LCA causative genes. By integrating tissue-specific expression levels and phenotypic data on top of that network, a more comprehensive biological view will highlight key molecular players of retinal degeneration and unveil new RP disease candidates. PMID- 26267446 TI - Application of a Hybrid Forest Growth Model to Evaluate Climate Change Impacts on Productivity, Nutrient Cycling and Mortality in a Montane Forest Ecosystem. AB - Climate change introduces considerable uncertainty in forest management planning and outcomes, potentially undermining efforts at achieving sustainable practices. Here, we describe the development and application of the FORECAST Climate model. Constructed using a hybrid simulation approach, the model includes an explicit representation of the effect of temperature and moisture availability on tree growth and survival, litter decomposition, and nutrient cycling. The model also includes a representation of the impact of increasing atmospheric CO2 on water use efficiency, but no direct CO2 fertilization effect. FORECAST Climate was evaluated for its ability to reproduce the effects of historical climate on Douglas-fir and lodgepole pine growth in a montane forest in southern British Columbia, Canada, as measured using tree ring analysis. The model was subsequently used to project the long-term impacts of alternative future climate change scenarios on forest productivity in young and established stands. There was a close association between predicted sapwood production and measured tree ring chronologies, providing confidence that model is able to predict the relative impact of annual climate variability on tree productivity. Simulations of future climate change suggest a modest increase in productivity in young stands of both species related to an increase in growing season length. In contrast, results showed a negative impact on stemwood biomass production (particularly in the case of lodgepole pine) for established stands due to increased moisture stress mortality. PMID- 26267448 TI - Fetal Tissue Fallout. PMID- 26267447 TI - Expression of dengue virus NS3 protein in Drosophila alters its susceptibility to infection. AB - We developed a Drosophila model in which the dengue virus NS3 protein is expressed in a tissue specific and inducible manner. Dengue virus NS3 is a multifunctional protein playing a major role during viral replication. Both protease and helicase domains of NS3 are interacting with human and insect host proteins including innate immune components of the host machinery. We characterized the NS3 transgenic flies showing that NS3 expression did not affect fly development. To further study the links between NS3 and the innate immune response, we challenge the flies with gram-positive and gram-negative bacteria. Interestingly, the Drosophila transgenic flies expressing NS3 were more susceptible to bacterial infections than control flies. However ubiquitous or immune-specific NS3 expression affected neither the life span nor the response to a non-infectious stress of the flies. In conclusion, we generated a new in vivo system to study the functional impact of DENV NS3 protein on the innate immune response. PMID- 26267449 TI - Caring for Our Transgender Troops--The Negligible Cost of Transition-Related Care. PMID- 26267450 TI - Civil Rights and Health--Beyond Same-Sex Marriage. PMID- 26267451 TI - Planned Parenthood at Risk. PMID- 26267455 TI - High-Speed Electrochemical Imaging. AB - The design, development, and application of high-speed scanning electrochemical probe microscopy is reported. The approach allows the acquisition of a series of high-resolution images (typically 1000 pixels MUm(-2)) at rates approaching 4 seconds per frame, while collecting up to 8000 image pixels per second, about 1000 times faster than typical imaging speeds used up to now. The focus is on scanning electrochemical cell microscopy (SECCM), but the principles and practicalities are applicable to many electrochemical imaging methods. The versatility of the high-speed scan concept is demonstrated at a variety of substrates, including imaging the electroactivity of a patterned self-assembled monolayer on gold, visualization of chemical reactions occurring at single wall carbon nanotubes, and probing nanoscale electrocatalysts for water splitting. These studies provide movies of spatial variations of electrochemical fluxes as a function of potential and a platform for the further development of high speed scanning with other electrochemical imaging techniques. PMID- 26267454 TI - Budgetary impact of treating acute promyelocytic leukemia patients with first line arsenic trioxide and retinoic acid from an Italian payer perspective. AB - The objective of this study was to estimate the net cost of arsenic trioxide (ATO) added to all-trans retinoic acid (ATRA) compared to ATRA plus chemotherapy when used in first-line acute promyelocytic leukemia (APL) treatment for low to intermediate risk patients from the perspective of the overall Italian healthcare systemA Markov model was developed with 3 health states: stable disease, disease event and death. Each month, patients could move from stable to disease event or die from either state. After a disease event, patients discontinued initial treatment and switched to the other regimen as second-line therapy. Treatment regimens, efficacy and adverse events were derived from published sources and expert opinion; unit costs were collected from standard Italian sources. Clinical outcomes and costs for pre-ATO and post-ATO scenarios were combined with population and product utilization information to calculate the total budgetary impact using a 3-year time horizon; one-way sensitivity analyses were conducted. Three-year cumulative pharmacy costs for ATO+ATRA were ?46,700 per-patient versus ?6,500 for ATRA+chemotherapy; however, medical costs for ATO+ATRA were ?12,300 per-patient versus ?30,200 for ATRA+chemotherapy. The total budgetary impact was estimated to be an additional ?127,300, ?312,500 and ?477,800 in the first, second and third years, respectively. The model was most sensitive to changes in the cost of the ATO+ATRA regimen during the consolidation phase. Budgetary impact models are valuable to payers making formulary decisions regarding the access and affordability of new medicines. The cost of treatment analysis showed that pharmacy costs for ATO+ATRA were higher than for ATRA+chemotherapy, while all other evaluated costs were lower for ATO+ATRA treated patients. The average budgetary impact was ?305,900 per year overall, representing a 3.5% increase. Further research is needed to determine the cost-effectiveness of ATO+ATRA compared to the current first-line standard of care in APL. PMID- 26267456 TI - Decomposition of multilayer benzene and n-hexane films on vanadium. AB - Reactions of multilayer hydrocarbon films with a polycrystalline V substrate have been investigated using temperature-programmed desorption and time-of-flight secondary ion mass spectrometry. Most of the benzene molecules were dissociated on V, as evidenced by the strong depression in the thermal desorption yields of physisorbed species at 150 K. The reaction products dehydrogenated gradually after the multilayer film disappeared from the surface. Large amount of oxygen was needed to passivate the benzene decomposition on V. These behaviors indicate that the subsurface sites of V play a role in multilayer benzene decomposition. Decomposition of the n-hexane multilayer films is manifested by the desorption of methane at 105 K and gradual hydrogen desorption starting at this temperature, indicating that C-C bond scission precedes C-H bond cleavage. The n-hexane dissociation temperature is considerably lower than the thermal desorption temperature of the physisorbed species (140 K). The n-hexane multilayer morphology changes at the decomposition temperature, suggesting that a liquid like phase formed after crystallization plays a role in the low-temperature decomposition of n-hexane. PMID- 26267453 TI - Determinants of adherence to treatment in hypertensive patients of African descent and the role of culturally appropriate education. AB - BACKGROUND: In Western countries, better knowledge about patient-related determinants of treatment adherence (medication and lifestyle) is needed to improve treatment adherence and outcomes among hypertensive ethnic minority patients of African descent. OBJECTIVE: To identify patient-related determinants of adherence to lifestyle and medication recommendations among hypertensive African Surinamese and Ghanaian patients with suboptimal treatment results (SBP>=140) living in the Netherlands and how culturally appropriate hypertension education (CAHE) influenced those determinants. METHODS: This study analysed data of 139 patients who participated in the CAHE trial. Univariate logistic regression analysis was used to measure the association between patient-related determinants (medication self-efficacy, beliefs about medication and hypertension, social support, and satisfaction with care) and treatment adherence. We also tested whether CAHE influenced the determinants. RESULTS: Medication self-efficacy and social support were associated with medication adherence at baseline. At six months, more medication self-efficacy and fewer concerns about medication use were associated with improved medication adherence. Self-efficacy was also associated with adherence to lifestyle recommendations at baseline. CAHE influenced patients' illness perceptions by creating more understanding of hypertension, its chronic character, and more concerns about the associated risks. CONCLUSION: In this high-risk population, health care providers can support medication adherence by paying attention to patients' medication self efficacy, the concerns they may have about medication use and patients' perceptions on hypertension. The CAHE intervention improved patients' perception on hypertension. PMID- 26267457 TI - Baseline Hematologic Results for Free-ranging White Rhinoceros (Ceratotherium simum) in Kruger National Park, South Africa. AB - Complete blood counts (n = 115) and red blood cell analytes (n = 80) were assessed in free-ranging white rhinoceros (Ceratotherium simum) from Kruger National Park (KNP), South Africa. Blood was collected from healthy animals immobilized between February and September 2009-11 for management purposes. Our objectives were to establish baselines for KNP's white rhinoceros population and to compare results based on sex and age group. Significant differences in total white blood cells, total eosinophils, and hemoglobin were found between adult and subadult rhinoceros. Female rhinoceros had significantly higher total white blood cells and lower hemoglobin compared with males. Hematologic analytes were similar to those published for other rhinoceros populations, although the impact of capture and sampling methods, nutritional status, and habitat should be considered when comparing data. This baseline hematology for healthy free-ranging white rhinoceros in KNP may be useful in assessing health status for translocation and medical interventions, including treatment of poaching cases. PMID- 26267459 TI - Rabies Virus Infection in Ferret Badgers (Melogale moschata subaurantiaca) in Taiwan: A Retrospective Study. AB - Fifteen ferret badgers (Melogale moschata subaurantiaca), collected 2010-13 and stored frozen, were submitted for rabies diagnosis by direct fluorescent antibody test and reverse transcription PCR. We detected seven positive animal samples, including some from 2010, which indicated that the ferret badger population in Taiwan had been affected by rabies prior to 2010. PMID- 26267460 TI - Serologic Evidence for Babesia bigemina Infection in Wild Yak (Bos mutus) in Qinghai Province, China. AB - Piroplasmosis, caused by tick-borne protozoan parasites of the genera Theileria and Babesia, is one of the most economically important infections of domestic ruminants in China. We evaluated the prevalence of antibodies to Babesia bigemina in wild yaks (Bos mutus) from Qinghai Province, China. Of 91 samples, 24% had detectable B. bigemina antibodies, and significant differences in prevalence were observed between those older than 5 yr and those younger than 5 yr. We collected 1,679 ticks belonging to two Ixodid genera from the infested wild yaks. The most prevalent tick species was Dermacentor nuttalli (48.1%), followed by Haemaphysalis qinghaiensis (33.3%) and Dermacentor silvarum (18.6%). These results indicated that B. bigemina is most likely endemic in the study area, and active surveillance programs for piroplasmosis are needed for monitoring animal health status. PMID- 26267461 TI - Direct Detection of Escherichia coli Virulence Genes by Real-Time PCR in Fecal Samples from Bats in Brazil. AB - Guano samples from 412 Brazilian bats were screened with real-time PCR for the virulence genes (eae, est, elt, stx1, stx2, ehxA, invA, bfpA, aggR) representing five intestinal pathotypes of Escherichia coli. From 82 pooled samples, 22% contained Escherichia coli DNA, and eae, est, bfpA, aggR were detected. PMID- 26267462 TI - Interactions between the Avian Parasite, Philornis downsi (Diptera: Muscidae) and the Galapagos Flycatcher, Myiarchus magnirostris Gould (Passeriformes: Tyrannidae). AB - An incidental observation of the fly Philornis downsi parasitizing a Galapagos Flycatcher (Myiarchus magnirostris) nest has revealed new insights into the searching behavior and biology of this invasive fly parasite and its interactions with endemic landbirds in the Galapagos Islands. Observations suggest that P. downsi relies on olfactory cues, or olfactory cues combined with the activity of adult birds, to locate nests and that flies continue to visit nests when chicks are >3 d old. At least 200 eggs were laid by P. downsi in different parts of the nest and >40 early-instar larvae were found inside the head of one chick, with additional larvae found in the base of the nest. Parasitism was the likely cause of mortality of both chicks found in or near the nest. This description of P. downsi parasitizing chicks of M. magnirostris highlights the vulnerability of this endemic bird species to this invasive fly. PMID- 26267463 TI - A Serosurvey for Brucellosis in Wild Boar (Sus scrofa) in Sardinia, Italy. AB - Porcine brucellosis is a zoonotic disease caused by Brucella suis and hosted by pigs (Sus scrofa). Both domestic pigs and wild boars are affected. We measured the prevalence of antibody to Brucella spp. in wild boars in Sardinia, Italy. During 1 November 2009 to 31 January 2010, we collected 570 serum samples from legally hunted wild boars and tested them using a commercial competitive enzyme linked immunosorbent assay. Sex and age class of the sampled wild boars were also recorded. Thirty-five samples were positive for an apparent antibody prevalence of 6.1%. Antibody prevalences did not differ between sexes or among age classes. PMID- 26267464 TI - COMPARISON OF MODIFIED FLOTAC AND BAERMANN TECHNIQUES FOR QUANTIFYING LUNGWORM LARVAE IN FREE-RANGING BIGHORN SHEEP (OVIS CANADENSIS) FECES, MONTANA, USA. AB - Lungworms are important parasites of wildlife and host infection status is often evaluated using coprologic techniques, most commonly the Baermann method. Recently, the FLOTAC(r) has emerged as a new tool for diagnosing lungworm infections, and methodologic comparison studies in domestic species suggest that this method outperforms many other established techniques. We compared a modified FLOTAC with the beaker-modified (bm)-Baermann to evaluate the relative performance of the two techniques for counting lungworm larvae in bighorn sheep (Ovis canadensis) feces. Both methods generated equivalent larval counts and both were highly repeatable. The major difference between the two methods was that the FLOTAC was poorer at detecting mixed infections. The ultimate choice between using the FLOTAC and bm-Baermann methods for quantifying lungworm larvae in wildlife studies may depend on the specific nature of the research questions being addressed, balanced by practical constraints. PMID- 26267465 TI - Sampling of Sea Ducks for Influenza A Viruses in Alaska during Winter Provides Lack of Evidence for Epidemiologic Peak of Infection. AB - Sampling of sea ducks for influenza A viruses in Alaska during winter provided no evidence for an epidemiologic peak of infection. Isolates were recovered, however, that provide information on viral diversity and dispersal that may not be realized through sampling efforts focused on other avian taxa. PMID- 26267468 TI - Moritz Kaposi: A Notable Name in Dermatology. PMID- 26267469 TI - Buzzwords in Dermatology: Opening a Can of Worms. PMID- 26267470 TI - Dermatology and the American Experience in Space. PMID- 26267471 TI - Error in Author Name Tagging. PMID- 26267472 TI - Error in Figure Label and Caption. PMID- 26267473 TI - Length-based assessment of coral reef fish populations in the main and northwestern Hawaiian islands. AB - The coral reef fish community of Hawaii is composed of hundreds of species, supports a multimillion dollar fishing and tourism industry, and is of great cultural importance to the local population. However, a major stock assessment of Hawaiian coral reef fish populations has not yet been conducted. Here we used the robust indicator variable "average length in the exploited phase of the population ([Formula: see text])", estimated from size composition data from commercial fisheries trip reports and fishery-independent diver surveys, to evaluate exploitation rates for 19 Hawaiian reef fishes. By and large, the average lengths obtained from diver surveys agreed well with those from commercial data. We used the estimated exploitation rates coupled with life history parameters synthesized from the literature to parameterize a numerical population model and generate stock sustainability metrics such as spawning potential ratios (SPR). We found good agreement between predicted average lengths in an unfished population (from our population model) and those observed from diver surveys in the largely unexploited Northwestern Hawaiian Islands. Of 19 exploited reef fish species assessed in the main Hawaiian Islands, 9 had SPRs close to or below the 30% overfishing threshold. In general, longer-lived species such as surgeonfishes, the redlip parrotfish (Scarus rubroviolaceus), and the gray snapper (Aprion virescens) had the lowest SPRs, while short-lived species such as goatfishes and jacks, as well as two invasive species (Lutjanus kasmira and Cephalopholis argus), had SPRs above the 30% threshold. PMID- 26267474 TI - The Effect of DNA Sequence Directionality on G-Quadruplex Folding. AB - Sequence inversion in G-rich DNA from 5'->3' to 3'->5' exerts a substantial effect on the number of structures formed, while the type of G-quadruplex fold is in fact determined by the presence of K(+) or Na(+) ions. The melting temperatures of G-quadruplexes adopted by oligonucleotides with sequences in the 5'->3' direction are higher than those of their 3'->5' counterparts with both KCl and NaCl. CD, UV, and NMR spectroscopy demonstrates the importance of primary sequence for the structural diversity of G-quadruplexes. The changes introduced by mere sequence reversal of the G-rich DNA segment have a substantial impact on the polymorphic nature of the resulting G-quadruplexes and their potential physiological roles. The insights resulting from this study should enable extension of the empirical rules for the prediction of G-quadruplex topology. PMID- 26267475 TI - Glucocorticoid Receptor-DNA Dissociation Kinetics Measured in Vitro Reveal Exchange on the Second Time Scale. AB - The glucocorticoid receptor (GR) is a member of the steroid receptor family of ligand-activated transcription factors. Recent live cell imaging studies have revealed that interactions of GR with chromatin are highly dynamic, with average receptor residence times of only seconds. These findings were surprising because early kinetic studies found that GR-DNA interactions in vitro were much slower, having calculated residence times of minutes to hours. However, these latter analyses were conducted at a time when it was possible to work with only either partially purified holoreceptor or its purified but isolated DNA binding domain. Noting these limitations, we reexamined GR-DNA dissociation kinetics using a highly purified holoreceptor shown to be amenable to rigorous study. We first observe that GR-DNA interactions in vitro are not slow as previously thought but converge with in vivo behavior, having residence times of only seconds to tens of seconds. This rapid exchange is seen at six individual response elements and the multisite MMTV promoter used in live cell imaging. Second, GR dissociation rates are identical for all response elements. Thus, previously observed differences in receptor affinity toward these sequences are not due to differences in off rate but in on rate. Finally, dissociation kinetics are biphasic in character. A minimal kinetic model consistent with the data is that in which DNA-bound GR interconverts between states on a second time scale, with dissociation occurring via a multistep process. We speculate that receptor interconversion in this time frame can be recognized by the coregulatory proteins that interact with GR, leading to unique transcriptional responses. PMID- 26267476 TI - Progeny Clustering: A Method to Identify Biological Phenotypes. AB - Estimating the optimal number of clusters is a major challenge in applying cluster analysis to any type of dataset, especially to biomedical datasets, which are high-dimensional and complex. Here, we introduce an improved method, Progeny Clustering, which is stability-based and exceptionally efficient in computing, to find the ideal number of clusters. The algorithm employs a novel Progeny Sampling method to reconstruct cluster identity, a co-occurrence probability matrix to assess the clustering stability, and a set of reference datasets to overcome inherent biases in the algorithm and data space. Our method was shown successful and robust when applied to two synthetic datasets (datasets of two-dimensions and ten-dimensions containing eight dimensions of pure noise), two standard biological datasets (the Iris dataset and Rat CNS dataset) and two biological datasets (a cell phenotype dataset and an acute myeloid leukemia (AML) reverse phase protein array (RPPA) dataset). Progeny Clustering outperformed some popular clustering evaluation methods in the ten-dimensional synthetic dataset as well as in the cell phenotype dataset, and it was the only method that successfully discovered clinically meaningful patient groupings in the AML RPPA dataset. PMID- 26267477 TI - Item Anomaly Detection Based on Dynamic Partition for Time Series in Recommender Systems. AB - In recent years, recommender systems have become an effective method to process information overload. However, recommendation technology still suffers from many problems. One of the problems is shilling attacks-attackers inject spam user profiles to disturb the list of recommendation items. There are two characteristics of all types of shilling attacks: 1) Item abnormality: The rating of target items is always maximum or minimum; and 2) Attack promptness: It takes only a very short period time to inject attack profiles. Some papers have proposed item anomaly detection methods based on these two characteristics, but their detection rate, false alarm rate, and universality need to be further improved. To solve these problems, this paper proposes an item anomaly detection method based on dynamic partitioning for time series. This method first dynamically partitions item-rating time series based on important points. Then, we use chi square distribution (chi2) to detect abnormal intervals. The experimental results on MovieLens 100K and 1M indicate that this approach has a high detection rate and a low false alarm rate and is stable toward different attack models and filler sizes. PMID- 26267478 TI - Maize Domestication and Anti-Herbivore Defences: Leaf-Specific Dynamics during Early Ontogeny of Maize and Its Wild Ancestors. AB - As a consequence of artificial selection for specific traits, crop plants underwent considerable genotypic and phenotypic changes during the process of domestication. These changes may have led to reduced resistance in the cultivated plant due to shifts in resource allocation from defensive traits to increased growth rates and yield. Modern maize (Zea mays ssp. mays) was domesticated from its ancestor Balsas teosinte (Z. mays ssp. parviglumis) approximately 9000 years ago. Although maize displays a high genetic overlap with its direct ancestor and other annual teosintes, several studies show that maize and its ancestors differ in their resistance phenotypes with teosintes being less susceptible to herbivore damage. However, the underlying mechanisms are poorly understood. Here we addressed the question to what extent maize domestication has affected two crucial chemical and one physical defence traits and whether differences in their expression may explain the differences in herbivore resistance levels. The ontogenetic trajectories of 1,4-benzoxazin-3-ones, maysin and leaf toughness were monitored for different leaf types across several maize cultivars and teosinte accessions during early vegetative growth stages. We found significant quantitative and qualitative differences in 1,4-benzoxazin-3-one accumulation in an initial pairwise comparison, but we did not find consistent differences between wild and cultivated genotypes during a more thorough examination employing several cultivars/accessions. Yet, 1,4-benzoxazin-3-one levels tended to decline more rapidly with plant age in the modern maize cultivars. Foliar maysin levels and leaf toughness increased with plant age in a leaf-specific manner, but were also unaffected by domestication. Based on our findings we suggest that defence traits other than the ones that were investigated are responsible for the observed differences in herbivore resistance between teosinte and maize. Furthermore, our results indicate that single pairwise comparisons may lead to false conclusions regarding the effects of domestication on defensive and possibly other traits. PMID- 26267480 TI - Survey of microbial contamination and characterization of Escherichia coli in kiwifruit orchards in Shaanxi, China, 2013. AB - The aim of the study was to survey three foodborne pathogens in kiwifruit orchards as a continuous monitoring program. A total of 193 samples were collected from 11 kiwifruit orchards in Shaanxi province in October 2013. Among the 193 samples, 68 Escherichia coli isolates were recovered, while no Staphylococcus aureus and Salmonella was recovered. All E. coli isolates were characterized by antimicrobial susceptibility testing, detection of virulence genes, and the ability to produce biofilm formation. The isolates were further examined by random amplified polymorphic DNA (RAPD) analysis. E. coli isolates displayed resistance most frequently to tetracycline (48.5%). Two E. coli isolates (2.9%) were positive for the eae gene (the intimin gene). All E. coli isolates lacked the ability to make biofilm formation. Multilocus sequence typing analysis demonstrated that one isolate in kiwifruit orchards shared the same sequence type with a human clinical isolate. RAPD results showed a close relationship among E. coli isolates from fresh fruit, fallen fruit, soil, air, and irrigation water. This study could provide a further understanding of microbial contamination in kiwifruit orchards based on our previous study and help growers take appropriate measures for prevention. PMID- 26267479 TI - Alzheimer's Disease-Related Protein Expression in the Retina of Octodon degus. AB - New studies show that the retina also undergoes pathological changes during the development of Alzheimer's disease (AD). While transgenic mouse models used in these previous studies have offered insight into this phenomenon, they do not model human sporadic AD, which is the most common form. Recently, the Octodon degus has been established as a sporadic model of AD. Degus display age-related cognitive impairment associated with Abeta aggregates and phosphorylated tau in the brain. Our aim for this study was to examine the expression of AD-related proteins in young, adult and old degus retina using enzyme-linked or fluorescence immunohistochemistry and to quantify the expression using slot blot and western blot assays. Abeta4G8 and Abeta6E10 detected Abeta peptides in some of the young animals but the expression was higher in the adults. Abeta peptides were observed in the inner and outer segment of the photoreceptors, the nerve fiber layer (NFL) and ganglion cell layer (GCL). Expression was higher in the central retinal region than in the retinal periphery. Using an anti-oligomer antibody we detected Abeta oligomer expression in the young, adult and old retina. Immunohistochemical labeling showed small discrete labeling of oligomers in the GCL that did not resemble plaques. Congo red staining did not result in green birefringence in any of the animals analyzed except for one old (84 months) animal. We also investigated expression of tau and phosphorylated tau. Expression was seen at all ages studied and in adults it was more consistently observed in the NFL-GCL. Hyperphosphorylated tau detected with AT8 antibody was significantly higher in the adult retina and it was localized to the GCL. We confirm for the first time that Abeta peptides and phosphorylated tau are expressed in the retina of degus. This is consistent with the proposal that AD biomarkers are present in the eye. PMID- 26267481 TI - Kinetics of IO Production in the CH2I + O2 Reaction Studied by Cavity Ring-Down Spectroscopy. AB - Cavity ring-down spectroscopy was used to study the kinetics of formation of IO radicals in the reaction of CH2I + O2 in a flow cell at 52 +/- 3 Torr total pressure of N2 diluent and a temperature of 295 K. CH2I was produced by photolysis of CH2I2 at 355 nm and IO probed on the A(2)Pi3/2-X(2)Pi3/2 (3,0) and (3,1) bands at 435.70 and 448.86 nm, respectively. The rates of formation of IO(v" = 0) and IO(v" = 1) were measured as a function of O2 number density using either conventional transient absorption or the simultaneous kinetic and ring down technique, respectively. IO(v" = 1) was found to be formed with a significantly larger rate constant, but reached far smaller peak concentrations than IO(v" = 0). Kinetic modeling supports the conclusion that IO(v" = 0) is produced both directly and through secondary chemistry, most probably involving the initial formation of the Criegee intermediate CH2OO and subsequent reaction with I atoms, while IO(v" = 1) is produced exclusively via a direct mechanism. We propose that the reaction mechanism (direct or indirect) depends upon the degree of initial excitation of the photolytically produced CH2I reagent. PMID- 26267482 TI - Evaluating the Effects of Land Use Planning for Non-Point Source Pollution Based on a System Dynamics Approach in China. AB - Urbanization is proceeding rapidly in several developing countries such as China. This accelerating urbanization alters the existing land use types in a way that results in more Non-Point Source (NPS) pollution to local surface waters. Reasonable land use planning is necessary. This paper compares seven planning scenarios of a case study area, namely Wulijie, China, from the perspective of NPS pollution. A System Dynamics (SD) model was built for the comparison to adequately capture the planning complexity. These planning scenarios, which were developed by combining different land use intensities (LUIs) and construction speeds (CSs), were then simulated. The results show that compared to scenario S1 (business as usual) all other scenarios will introduce more NPS pollution (with an incremental rate of 22%-70%) to Wulijie. Scenario S6 was selected as the best because it induced relatively less NPS pollution while simultaneously maintaining a considerable development rate. Although LUIs represent a more critical factor compared to CSs, we conclude that both LUIs and CSs need to be taken into account to make the planning more environmentally friendly. Considering the power of SD in decision support, it is recommended that land use planning should take into consideration findings acquired from SD simulations. PMID- 26267483 TI - Discovery of 4-Amino-8-quinoline Carboxamides as Novel, Submicromolar Inhibitors of NAD-Hydrolyzing Enzyme CD38. AB - Starting from the micromolar 8-quinoline carboxamide high-throughput screening hit 1a, a systematic exploration of the structure-activity relationships (SAR) of the 4-, 6-, and 8-substituents of the quinoline ring resulted in the identification of approximately 10-100-fold more potent human CD38 inhibitors. Several of these molecules also exhibited pharmacokinetic parameters suitable for in vivo animal studies, including low clearances and decent oral bioavailability. Two of these CD38 inhibitors, 1ah and 1ai, were shown to elevate NAD tissue levels in liver and muscle in a diet-induced obese (DIO) C57BL/6 mouse model. These inhibitor tool compounds will enable further biological studies of the CD38 enzyme as well as the investigation of the therapeutic implications of NAD enhancement in disease models of abnormally low NAD. PMID- 26267485 TI - Progress toward the Quantitative Analysis of PAHs Adsorbed on Soot by Laser Desorption/Laser Ionization/Time-of-Flight Mass Spectrometry. AB - Ex situ analyses of substances extracted from flames provide useful albeit mostly qualitative information on the formation process of soot and on the impact of exhausts on the environment. An experimental setup based on the coupling of laser desorption, laser ionization and time-of-flight mass spectrometry (LD/LI/ToF-MS) is presented in past works as an alternative means to more traditional techniques like gas chromatography (GC) to characterize the polycyclic aromatic hydrocarbons (PAHs) content of soot. In this paper, we go one step further in the understanding of the laser desorption/laser ionization dynamics and propose a combined experimental/simulation approach: we estimate the limit of detection of LD/LI/ToF-MS as low as [0.2, 2.8] fmol per laser pulse and we make quantitative predictions on the concentration of PAHs desorbed from soot. In particular, external calibration with model samples where PAHs are adsorbed on black carbon at known concentrations allows us to link the concentration of PAHs desorbed and detected by photoionization ToF-MS to the concentration of PAHs adsorbed on soot. The comparison of data obtained from the analysis of flame sampled soot with standard commercial GC-MS run in parallel validates the approach and defines limits and potentialities of both techniques. PMID- 26267484 TI - Survey of sand flies (Diptera: Psychodidae) in an environmentally protected area in Brazil. AB - Brazil is one of the most important endemic areas for leishmaniasis worldwide. Protected areas that are tourist attractions likely present an important risk of transmission of cutaneous leishmaniasis (CL). Furthermore, with the geographical expansion of visceral leishmaniasis (VL), several studies have recorded the occurrence of its vector, Lutzomyia longipalpis, and cases of human and canine VL in such tourist areas. The Parque Estadual do Sumidouro is an environmentally protected area located in the Brazilian Cerrado biome and in an important area endemic for leishmaniasis in the state of Minas Gerais. The purpose of this study was to monitor the sand fly fauna in areas of tourist activity in the park. Sampling was performed every month, from September 2011 to August 2013, using CDC light traps at six sites of differing environmental characteristics. Sampled specimens were identified following Galati (2003), and females were submitted to molecular techniques for the detection and identification of Leishmania DNA. A total of 4,675 sand fly specimens of 25 species belonging to nine genera were collected. The most abundant species were Micropygomyia quinquefer, Lutzomyia renei and Pintomyia pessoai, although only Pi. pessoai is implicated in the transmission of Leishmania braziliensis. The species accumulation curve reached saturation on the 16th sampling event. Species richness, diversity and evenness differed among the sampled areas. The seasonal curve was not determined by a single unique species, and no single species was the most abundant in all environments sampled. The main vector of Leishmania (Leishmania) infantum, Lutzomyia longipalpis, accounted for only 5.35% of the specimens collected. Proven or suspected vectors of Leishmania (Viannia) braziliensis were recorded, and one female of the cortellezzii complex tested positive for Le. braziliensis DNA. Even with a low infection rate (0.62%), these data indicate the circulation of the parasite and reinforce the need for entomological and epidemiological surveillance in the park and its surroundings. PMID- 26267486 TI - MCF-7 Human Breast Cancer Cells Form Differentiated Microtissues in Scaffold-Free Hydrogels. AB - Three-dimensional (3D) cultures are increasing in use because of their ability to represent in vivo human physiology when compared to monolayer two-dimensional (2D) cultures. When grown in 3D using scaffold-free agarose hydrogels, MCF-7 human breast cancer cells self-organize to form directionally-oriented microtissues that contain a luminal space, reminiscent of the in vivo structure of the mammary gland. When compared to MCF-7 cells cultured in 2D monolayer culture, MCF-7 microtissues exhibit increased mRNA expression of luminal epithelial markers keratin 8 and keratin 19 and decreased expression of basal marker keratin 14 and the mesenchymal marker vimentin. These 3D MCF-7 microtissues remain responsive to estrogens, as demonstrated by induction of known estrogen target mRNAs following exposure to 17beta-estradiol. Culture of MCF-7 cells in scaffold-free conditions allows for the formation of more differentiated, estrogen-responsive structures that are a more relevant system for evaluation of estrogenic compounds than traditional 2D models. PMID- 26267487 TI - Beneficial effects of hyperbaric oxygen on edema in rat hippocampus following traumatic brain injury. AB - Hyperbaric oxygen (HBO) therapy helps alleviate secondary injury following brain trauma [traumatic brain injury (TBI)], although the mechanisms remain unclear. In this study, we assessed recovery of post-TBI spatial learning and memory in rats using the Morris water maze (MWM) and measured changes in apparent diffusion coefficient in the hippocampus by diffusion-weighted imaging (DWI) to evaluate possible therapeutic effects of HBO on TBI-associated brain edema. DWIs were obtained 8, 24, 48 h, 7 days, and 14 days post-TBI. Daily HBO therapy significantly improved post-TBI MWM performance and reduced edema in the ipsilateral hippocampus, suggesting that the therapeutic efficacy of HBO is mediated, at least in part, by a reduction in brain edema. PMID- 26267489 TI - Editor's perspectives--August 2015. PMID- 26267488 TI - New Routes to Phylogeography: A Bayesian Structured Coalescent Approximation. AB - Phylogeographic methods aim to infer migration trends and the history of sampled lineages from genetic data. Applications of phylogeography are broad, and in the context of pathogens include the reconstruction of transmission histories and the origin and emergence of outbreaks. Phylogeographic inference based on bottom-up population genetics models is computationally expensive, and as a result faster alternatives based on the evolution of discrete traits have become popular. In this paper, we show that inference of migration rates and root locations based on discrete trait models is extremely unreliable and sensitive to biased sampling. To address this problem, we introduce BASTA (BAyesian STructured coalescent Approximation), a new approach implemented in BEAST2 that combines the accuracy of methods based on the structured coalescent with the computational efficiency required to handle more than just few populations. We illustrate the potentially severe implications of poor model choice for phylogeographic analyses by investigating the zoonotic transmission of Ebola virus. Whereas the structured coalescent analysis correctly infers that successive human Ebola outbreaks have been seeded by a large unsampled non-human reservoir population, the discrete trait analysis implausibly concludes that undetected human-to-human transmission has allowed the virus to persist over the past four decades. As genomics takes on an increasingly prominent role informing the control and prevention of infectious diseases, it will be vital that phylogeographic inference provides robust insights into transmission history. PMID- 26267490 TI - Autofluorescence imaging in recurrent oral squamous cell carcinoma. AB - The survival of patients with oral cancer is decreased by locoregional recurrence after an initial multimodal treatment. In order to identify lesions in the oral cavity for a possible recurrence, clinical evaluation as well as MRI or CT scanning is advised. The evaluation of mucosa lesions is hampered by changes related to radio- and chemotherapy as well as reconstruction with tissue flaps. Several techniques for easier identification of tissue abnormalities in the oral cavity have been advocated as adjuncts in order to facilitate identification. Especially methods using altered tissue fluorescence have gained much interest during the last decade. The aim of our prospective study was to evaluate fluorescence properties of undiagnosed mucosa lesions with the VELscope device in patients with multimodal treated oral cancer prior to histological confirmation. In total, 41 patients with a history of oral squamous cell carcinomas (OSCC) (19 females and 22 males) with undiagnosed mucosa lesions where included in the study. After clinical evaluation, examination and documentation using the VELscope(r) device were performed. Then, an incisional biopsy was performed. An autofluorescence loss indicating a malignant or dysplastic mucosa condition could be detected in six patients (14.6 %); however, only one OSCC and one SIN revealed a complete autofluorescence loss. In four patients, OSCC was present in lesions with retained autofluorescence. Sensitivity and specificity for the VELscope(r) examination to identify malignant oral lesions by autofluorescence were 33.3 and 88.6 %, respectively. The positive and negative predictive values were 33.3 and 88.6 %, respectively. No statistical correlation between gender and lesion appearance versus autofluorescence loss could be detected. In contrast to mucosa lesions in patients with no prior treatment, the autofluorescence evaluation with the VELscope reveals no additional information in our analysis. Accordingly, invasive biopsies as gold standard are still needed to get sufficient evidence regarding potential malignancy in patients after multimodal treatment for oral cancer. PMID- 26267491 TI - How long is too long in contemporary peer review? Perspectives from authors publishing in conservation biology journals. AB - Delays in peer reviewed publication may have consequences for both assessment of scientific prowess in academics as well as communication of important information to the knowledge receptor community. We present an analysis on the perspectives of authors publishing in conservation biology journals regarding their opinions on the importance of speed in peer-review as well as how to improve review times. Authors were invited to take part in an online questionnaire, of which the data was subjected to both qualitative (open coding, categorizing) and quantitative analyses (generalized linear models). We received 637 responses to a total of 6,547 e-mail invitations sent. Peer-review speed was generally perceived as slow, with authors experiencing a typical turnaround time of 14 weeks while their perceived optimal review time is six weeks. Male and younger respondents seem to have higher expectations of review speed than females and older respondents. Majority of participants attributed lengthy review times to the 'stress' on the peer-review system (i.e., reviewer and editor fatigue), while editor persistence and journal prestige were believed to speed up the review process. Negative consequences of lengthy review times appear to be greater for early career researchers and can also have impact on author morale (e.g. motivation or frustration). Competition among colleagues were also of concern to respondents. Incentivizing peer review was among the top suggested alterations to the system along with training graduate students in peer review, increased editorial persistence, and changes to the norms of peer-review such as opening the peer review process to the public. It is clear that authors surveyed in this study view the peer-review system as under stress and we encourage scientists and publishers to push the envelope for new peer review models. PMID- 26267492 TI - Distinct vasopressin content in the hypothalamic supraoptic and paraventricular nucleus of rats exposed to low and high ambient temperature. AB - Both high and low ambient temperature represent thermal stressors that, among other physiological responses, induce activation of the hypothalamic-pituitary adrenal (HPA) axis and secretion of arginine-vasopressin (AVP). The exposure to heat also leads to disturbance of osmotic homeostasis. Since AVP, in addition to its well-known peripheral effects, has long been recognized as a hormone involved in the modulation of HPA axis activity, the aim of the present study was to elucidate the hypothalamic AVP amount in the acutely heat/cold exposed rats. Rats were exposed to high (+38 degrees C) or low (+4 degrees C) ambient temperature for 60min. Western blot was employed for determining hypothalamic AVP levels, and the difference in its content between supraoptic (SON) and paraventricular nucleus (PVN) was detected using immunohistochemical analysis. The results showed that exposure to both high and low ambient temperature increased hypothalamic AVP levels, although the increment was higher under heat conditions. On the other hand, patterns of AVP level changes in PVN and SON were stressor-specific, given that exposure to cold increased the AVP level in both nuclei, while heat exposure affected the PVN AVP content alone. In conclusion, our results revealed that cold and heat stress influence hypothalamic AVP amount with different intensity. Moreover, different pattern of AVP amount changes in the PVN and SON indicates a role of this hormone not only in response to heat as an osmotic/physical threat, but to the non-osmotic stressors as well. PMID- 26267493 TI - Effect of heat stress-induced production of mitochondrial reactive oxygen species on NADPH oxidase and heme oxygenase-1 mRNA levels in avian muscle cells. AB - Heat stress is a major factor inducing oxidative disturbance in cells. In the present study, we investigated the mechanism of overproduction of reactive oxygen species (ROS) in cultured avian muscle cells in response to heat stress, and also focused attention on the interaction of mitochondrial superoxide anions with altered NADPH oxidase (NOX), superoxide dismutase (SOD) and heme oxygenase-1 (HO 1) mRNA levels in heat-stressed cells. Exposure of cells to heat stress conditions (41 degrees C, 6h) resulted in increased mitochondrial superoxide and intracellular ROS levels, and increased carbonyl protein content as compared with that of normal cells (37 degrees C). The mitochondrial uncoupler 2,4 dinitrophenol lowered intracellular ROS levels in heat-stressed cells. Heat stress increased NOX4 mRNA and decreased HO-1 mRNA levels, while SOD1 and SOD2 mRNA levels remained relatively stable in heat-stressed cells. Addition of the superoxide scavenger 4-hydroxy TEMPO to the culture medium of heat-stressed cells restored mitochondrial superoxide and intracellular ROS levels as well as NOX4 and HO-1 mRNA levels to near-normal values. We suggest that mitochondrial superoxide production could play an influential role in augmenting oxidative damage to avian muscle cells, possibly via the up-regulation of NOX4 and down regulation of HO-1 in heat-stressed avian muscle cells. PMID- 26267494 TI - Potential for thermal tolerance to mediate climate change effects on three members of a cool temperate lizard genus, Niveoscincus. AB - Climatic changes are predicted to be greater in higher latitude and mountainous regions but species specific impacts are difficult to predict. This is partly due to inter-specific variance in the physiological traits which mediate environmental temperature effects at the organismal level. We examined variation in the critical thermal minimum (CTmin), critical thermal maximum (CTmax) and evaporative water loss rates (EWL) of a widespread lowland (Niveoscincus ocellatus) and two range restricted highland (N. microlepidotus and N. greeni) members of a cool temperate Tasmanian lizard genus. The widespread lowland species had significantly higher CTmin and CTmax and significantly lower EWL than both highland species. Implications of inter-specific variation in thermal tolerance for activity were examined under contemporary and future climate change scenarios. Instances of air temperatures below CTmin were predicted to decline in frequency for the widespread lowland and both highland species. Air temperatures of high altitude sites were not predicted to exceed the CTmax of either highland species throughout the 21st century. In contrast, the widespread lowland species is predicted to experience air temperatures in excess of CTmax on 1 or 2 days by three of six global circulation models from 2068-2096. To estimate climate change effects on activity we reran the thermal tolerance models using minimum and maximum temperatures selected for activity. A net gain in available activity time was predicted under climate change for all three species; while air temperatures were predicted to exceed maximum temperatures selected for activity with increasing frequency, the change was not as great as the predicted decline in air temperatures below minimum temperatures selected for activity. We hypothesise that the major effect of rising air temperatures under climate change is an increase in available activity period for both the widespread lowland and highland species. The consequences of a greater available activity period will depend on the extent to which changes in climate alters other related factors, such as the nature and level of competition between the respective species. PMID- 26267495 TI - Molecular characterization and expression analysis of hsp60 gene homologue of sheep blowfly, Lucilia cuprina. AB - The 60kDa heat shock protein (Hsp60) or chaperonin is one among the highly conserved families of heat shock proteins, known to be involved in variety of cellular activities, including protein folding, thermal protection, etc. In this study we sequence characterized hsp60 gene homologue of Lucilia cuprina, isolated and cloned from the genomic library as well as by genomic PCR, followed by RACE- PCR. The L. cuprina hsp60 gene/protein expression pattern was analyzed in various tissues, either at normal temperature (25+/-1 degrees C) or after exposure to heat stress (42 degrees C). The analysis of nucleotide sequence of Lchsp60 gene revealed absence of intron and the nuclear localizing signal (NLS). The deduced amino acid sequence showed presence of unique conserved sequences, such as those for mitochondrial localization, ATP binding, etc. Unlike Drosophila, Lucilia showed presence of only one isoform, i.e., hsp60A. Phylogenetic analysis of hsp60 gene homologues from different species revealed Lchsp60 to have >88.36% homology with D. melanogaster, 76.86% with L. sericata, 58.31% with mice, 57.99% with rat, and 57.72% with human. Expression analysis using Real Time PCR and fluorescence imaging showed significant enhancement in the expression level of Lchsp60 upon heat stress in a tissue specific manner, indicating its likely role in thermo tolerance as well as in normal cellular activities. PMID- 26267496 TI - A prediction model for ocular damage - Experimental validation. AB - With the increasing number of laser applications in medicine and technology, accidental as well as intentional exposure of the human eye to laser sources has become a major concern. Therefore, a prediction model for ocular damage (PMOD) is presented within this work and validated for long-term exposure. This model is a combination of a raytracing model with a thermodynamical model of the human and an application which determines the thermal damage by the implementation of the Arrhenius integral. The model is based on our earlier work and is here validated against temperature measurements taken with porcine eye samples. For this validation, three different powers were used: 50mW, 100mW and 200mW with a spot size of 1.9mm. Also, the measurements were taken with two different sensing systems, an infrared camera and a fibre optic probe placed within the tissue. The temperatures were measured up to 60s and then compared against simulations. The measured temperatures were found to be in good agreement with the values predicted by the PMOD-model. To our best knowledge, this is the first model which is validated for both short-term and long-term irradiations in terms of temperature and thus demonstrates that temperatures can be accurately predicted within the thermal damage regime. PMID- 26267497 TI - Correction of the heat loss method for calculating clothing real evaporative resistance. AB - In the so-called isothermal condition (i.e., Tair [air temperature]=Tmanikin [manikin temperature]=Tr [radiant temperature]), the actual energy used for moisture evaporation detected by most sweating manikins was underestimated due to the uncontrolled fabric 'skin' temperature Tsk,f (i.e., Tsk,f31 degrees C) triggers both an increment in mglc and suppression of MUmax, which together contribute to an upshift of Yatp/glc from the lower limit and thus compensate for the loss of the safety margin. This trade off allows adding 10 more degrees to Topt and extends the thermal window up to 40 degrees C, sustaining survival and reproduction in supraoptimal temperatures. Deeper understanding of the limits of thermal tolerance can be practically exploited in biotechnological applications. PMID- 26267507 TI - Effects of graduated compression stockings on skin temperature after running. AB - High skin temperatures reduce the thermal gradient between the core and the skin and they can lead to a reduction in performance and increased risk of injury. Graduated compression stockings have become popular among runners in the last years and their use may influence the athlete's thermoregulation. The aim of this study was to investigate the effects of graduated compression stockings on skin temperature during running in a moderate indoor environment. Forty-four runners performed two running tests lasting 30min (10min of warm-up and 20min at 75% of their maximal aerobic speed) with and without graduated compressive stockings. Skin temperature was measured in 12 regions of interest on the lower limb by infrared thermography before and after running. Heart rate and perception of fatigue were assessed during the last minute of the running test. Compression stockings resulted in greater increase of temperature (p=0.002 and ES=2.2, 95% CI [0.11-0.45 degrees C]) not only in the body regions in contact (tibialis anterior, ankle anterior and gastrocnemius) but also in the body regions that were not in contact with the garment (vastus lateralis, abductor and semitendinosus). No differences were observed between conditions in heart rate and perception of fatigue (p>0.05 and ES<0.8). In conclusion, running with graduated compression stockings produces a greater increase of skin temperature without modifying the athlete's heart rate and perception of fatigue. PMID- 26267508 TI - A novel personal cooling system (PCS) incorporated with phase change materials (PCMs) and ventilation fans: An investigation on its cooling efficiency. AB - Personal cooling systems (PCS) have been developed to mitigate the impact of severe heat stress for humans working in hot environments. It is still a great challenge to develop PCSs that are portable, inexpensive, and effective. We studied the performance of a new hybrid PCS incorporating both ventilation fans and phase change materials (PCMs). The cooling efficiency of the newly developed PCS was investigated on a sweating manikin in two hot conditions: hot humid (HH, 34 degrees C, 75% RH) and hot dry (HD, 34 degrees C, 28% RH). Four test scenarios were selected: fans off with no PCMs (i.e., Fan-off, the CONTROL), fans on with no PCMs (i.e., Fan-on), fans off with fully solidified PCMs (i.e., PCM+Fan-off), and fans on with fully solidified PCMs (i.e., PCM+Fan-on). It was found that the addition of PCMs provided a 54~78min cooling in HH condition. In contrast, the PCMs only offered a 19-39min cooling in HD condition. In both conditions, the ventilation fans greatly enhanced the evaporative heat loss compared with Fan off. The hybrid PCS (i.e., PCM+Fan-on) provided a continuous cooling effect during the three-hour test and the average cooling rate for the whole body was around 111 and 315W in HH and HD conditions, respectively. Overall, the new hybrid PCS may be an effective means of ameliorating symptoms of heat stress in both hot-humid and hot-dry environments. PMID- 26267509 TI - Simultaneous estimation of size, radial and angular locations of a malignant tumor in a 3-D human breast - A numerical study. AB - This article reports a numerical study pertaining to simultaneous estimation of size, radial location and angular location of a malignant tumor in a 3-D human breast. The breast skin surface temperature profile is specific to a tumor of specific size and location. The temperature profiles are always the Gaussian one, though their peak magnitudes and areas differ according to the size and location of the tumor. The temperature profiles are obtained by solving the Pennes bioheat equation using the finite element method based solver COMSOL 4.3a. With temperature profiles known, simultaneous estimation of size, radial location and angular location of the tumor is done using the curve fitting method. Effect of measurement errors is also included in the study. Estimations are accurate, and since in the inverse analysis, the curve fitting method does not require solution of the governing bioheat equation, the estimation is very fast. PMID- 26267510 TI - Thermal ecology of the fiddler crab Uca panacea: Thermal constraints and organismal responses. AB - Temperature is one of the primary environmental variables limiting organismal performance, fitness, and species distributions. Yet, understanding temperature effects requires thorough exploration of thermal constraints and organismal responses that can translate to fitness and non-lethal long-term consequences under both constant and changing thermal regimes. We examined the thermal ecology of the fiddler crab Uca panacea, including critical thermal limits, thermal sensitivity of locomotion, operative environmental temperatures, preferred body temperatures, and acclimation ability. Operative environmental temperatures frequently reached the critical thermal maximum (41.8+/-0.8 degrees C, mean +/- s.e.m.), especially in unvegetated microhabitats, indicating the need for behavioral thermoregulation to maintain diurnal activity patterns. Preferred body temperatures (21.1-28.6 degrees C) were substantially below the thermal optimum (30-40 degrees C), although further research is needed to determine the driver of this mismatch. Critical thermal limits shifted 2-4 degrees C in response to exposure to low (20 degrees C) or high (35 degrees C) temperatures, with full acclimation occurring in approximately 9d. This capacity for rapid acclimation, combined with the capacity for behavioral thermoregulation, is a strong candidate mechanism that explains the broad habitat use and could help explain the successful pantropical distribution of fiddler crabs. PMID- 26267511 TI - Seasonal variation in thermal tolerance, oxygen consumption, antioxidative enzymes and non-specific immune indices of Indian hill trout, Barilius bendelisis (Hamilton, 1807) from central Himalaya, India. AB - We studied the season dependent thermal tolerance, oxygen consumption, respiratory burst response and antioxidative enzyme activities in juveniles of Barilius bendelisis. The critical thermal maximum (CTmax), lethal thermal maximum (LTmax), critical thermal minimum (CTmin) and lethal thermal minimum (LTmin) were significantly different at five different seasons viz. winter (10.64 degrees C), spring (16.25 degrees C), summer (22.11 degrees C), rainy (20.87 degrees C) and autumn (17.77 degrees C). The highest CTmax was registered in summer (36.02 degrees C), and lowest CTmin was recorded during winter (2.77 degrees C). Water temperature, dissolved oxygen and pH were strongly related to CTmax, LTmax, CTmin and LTmin suggesting seasonal acclimatization of B. bendelisis. The thermal tolerance polygon area of the B. bendelisis juveniles within the range of seasonal temperature (10.64-22.11 degrees C) was calculated as 470.92 degrees C(2). Oxygen consumption rate was significantly different (p<0.05) between seasons with maximum value during summer (57.66mgO2/kg/h) and lowest in winter (32.60mgO2/kg/h). Total white blood cell count including neutrophil and monocytes also showed significant difference (p<0.05) between seasons with maximum value during summer and minimum number in winter and were found correlated to temperature, dissolved oxygen, pH and respiratory burst activity. Respiratory burst activity of blood phagocytes significantly differed (p<0.05) among seasons with higher value during summer (0.163 OD540nm) and minimum in winter season (0.054 OD540nm). The activity of superoxide dismutase, catalase and glutathione-s transferase both in liver and gill, also varied significantly (p<0.05) during different seasons. Overall results of this study suggest that multiple environmental factors play a role in seasonal acclimation in B. bendelisis, which modulate the thermal tolerance, oxygen consumption, respiratory burst activity and status of anti-oxidative potential in wild environment. PMID- 26267512 TI - Human thermal physiological and psychological responses under different heating environments. AB - Anecdotal evidence suggests that many residents of severely cold areas of China who use floor heating (FH) systems feel warmer but drier compared to those using radiant heating (RH) systems. However, this phenomenon has not been verified experimentally. In order to validate the empirical hypothesis, and research the differences of human physiological and psychological responses in these two asymmetrical heating environments, an experiment was designed to mimic FH and RH systems. The subjects participating in the experiment were volunteer college students. During the experiment, the indoor air temperature, air speed, relative humidity, globe temperature, and inner surface temperatures were measured, and subjects' heart rate, blood pressure and skin temperatures were recorded. The subjects were required to fill in questionnaires about their thermal responses during testing. The results showed that the subjects' skin temperatures, heart rate and blood pressure were significantly affected by the type of heating environment. Ankle temperature had greatest impact on overall thermal comfort relative to other body parts, and a slightly cool FH condition was the most pleasurable environment for sedentary subjects. The overall thermal sensation, comfort and acceptability of FH were higher than that of RH. However, the subjects of FH felt drier than that of RH, although the relative humidity in FH environments was higher than that of the RH environment. In future environmental design, the thermal comfort of the ankles should be scrutinized, and a FH cool condition is recommended as the most comfortable thermal environment for office workers. Consequently, large amounts of heating energy could be saved in this area in the winter. The results of this study may lead to more efficient energy use for office or home heating systems. PMID- 26267513 TI - Source term prediction in a multilayer tissue during hyperthermia. AB - One of the major challenges in the use of hyperthermia to treat cancer is determining the desired heating power of external source in such a way that the thermal injury is confined to the unhealthy tissue. In this study, an inverse method based on the sequential method is proposed to estimate the desired heating power as a function of time for a successful hyperthermia treatment. In order to simulate the measured temperature, the direct problem is solved for a multilayer skin tissue to obtain the temperature data at the skin surface. These data are employed in the inverse problem to estimate the heating power of external source. Two examples are considered to examine the accuracy of the inverse analysis. In addition, the effect of measurement errors is investigated. Results show that the proposed inverse algorithm is able to determine the desired heating power of external source accurately, even in the presence of measurement errors. However, for noisy data, more temperature measurements are required to achieve reliable results. PMID- 26267514 TI - Could human cold adaptation decrease the risk of cardiovascular disease? AB - The impact of repeated exposure to cold and cold adaptation on human cardiovascular health is not fully understood. The aim of the study was to determine the effect of cold adaptation on cardiovascular risk factors, thyroid hormones and the capacity of humans to reset the damaging effect of oxidative stress. Ten well cold-adapted winter swimmers (CA) and 16 non-adapted controls (CON) were enroled in this experiment to test whether cold adaptation could influence the parameters of lipoprotein metabolism, cholesterol efflux capacity (CEC), homocysteine, thyroid hormones, antioxidant defence markers (reduced glutathione (GSH), glutathione peroxidase 1 (GPX1), glutathione reductase (GR), catalase (CAT) and paraoxonase 1 (PON1)) and oxidative stress markers (concentration of conjugated dienes (CD)). A decreased apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio was found in the CA group (p<0.05), but other lipoprotein parameters, including CEC, did not differ significantly. Plasma homocysteine was lower in CA subjects in comparison with controls (p<0.05). Higher triiodothyronine (T3) values were observed in the CA compared to the CON (p<0.05) group, but TSH and other thyroid hormones did not differ between both groups. CA subjects had lower activity of GPX1 (p<0.05), lower concentrations of CD (p<0.05) and increased activities of PON1 (p<0.001) compared to CON subjects. A trend for decreased activity of CAT (p=0.06) in CA compared to CON groups was also observed, but GSH levels did not differ significantly. Zn concentration was higher in the CA group than in the CON group (p<0.001). Human cold adaptation can influence oxidative stress markers. Trends towards the improvement of cardiovascular risk factors in cold-adapted subjects also indicate the positive effect of cold adaptation on cardio-protective mechanisms. PMID- 26267515 TI - Differential expression patterns among heat-shock protein genes and thermal responses in the whitefly Bemisia tabaci (MEAM 1). AB - There is convincing evidence that heat-shock proteins (HSP) are upregulated by stress conditions in insects; however, the relative contribution of each HSP gene to the heat-shock response remains unclear. Here we considered the whitefly Bemisia tabaci (MEAM 1), a phloem feeder and invasive species whose molecular stress response is an important mechanism for overcoming heat stress. We assessed the expression of the hsp23, 40, 70 and 90 genes at the mRNA level when submitted to heat shocks of 40 and 44 degrees C/1h (control at 25 degrees C). For this, we evaluated a set of available and suitable reference genes in order to perform data normalization using the real-time polymerase chain reaction (qRT-PCR) technique, and then confirmed the production of HSP70 protein based on Western blot. Results were compared with the hardening capacity of B. tabaci, measured by fitness components as a response to heat shocks, using 40 degrees C as the induction temperature. Three of the four genes (hsp23, 70 and 90) were upregulated by heat stress at mRNA, showing differential expression patterns. Hsp70 expression was confirmed at the protein level. Hardening significantly increased fitness following heat stress, suggesting that HSPs may contribute to hardening capacity in B. tabaci. Potential role of each gene in the heat-shock response for whiteflies is discussed. PMID- 26267516 TI - Energy expenditure of the spotted snow skink, Niveoscincus ocellatus, at two climatic extremes of its distribution range. AB - The study of energy expenditure between populations of a wide ranging ectothermic species may provide an insight into how organisms respond to variation in environmental conditions. In this study, the energy expenditure of male spotted snow skinks, Niveoscincus ocellatus, living at the two extremes of the species' distribution range (warm lowland versus cold alpine site) was measured using the doubly labelled water method. Males at the cold alpine site expended more energy per gram per hour compared to their counterparts living at the warm lowland site. Lizards living at high altitude were active at lower temperatures compared with those at the low altitude site, which resulted in a longer activity time for the highland population. However, the differences in energy expenditure cannot be explained only by these differences in activity time. We further suggest that at the cold alpine site, lizards compensated for the low temperatures by elevating their metabolism which subsequently increased their energy expenditure. An elevated metabolic rate combined with modified thermoregulatory behaviour is likely an important mechanism allowing N. ocellatus to cope with the cold environments at high altitude sites. PMID- 26267518 TI - Acid-base balance disturbances in plasma exchange depend on the replacement fluid used. AB - BACKGROUND: Metabolic alkalosis occurs as a direct result of plasma exchange (PE) because of metabolism of citrate. However, we observed a decrease of serum pH and bicarbonate after PE when albumin was used as replacement fluid. STUDY DESIGN AND METHODS: The acid-base balance in 2730 PEs using different replacement fluids (albumin, fresh-frozen plasma [FFP], or both) was measured, and absolute changes (Delta) in acid-base balance were compared. The frequency of adverse effects (AEs) before and after using prophylactic administration of sodium bicarbonate was compared. RESULTS: A decrease of serum pH and bicarbonate was observed after PEs when albumin was used as replacement fluid (Delta pH = -0.06 +/- 0.04; Delta bicarbonate = -4.03 +/- 2.29 mmol/L; Delta base excess = -2.54 +/- 3.82 mmol/L). An increase of serum pH and bicarbonate was observed after PEs when FFP was used as replacement fluid (Delta pH = +0.04 +/- 0.05; Delta bicarbonate = +3.6 +/- 3.68 mmol/L; Delta base excess = +1.62 +/- 4.51 mmol/L). The prophylactic administration of sodium bicarbonate corrected partially the decrease of serum pH and bicarbonate after finishing PEs when albumin was used as replacement fluid (Delta pH = -0.04 +/- 0.04; Delta bicarbonate = -3.1 +/- 2.47 mmol/L; Delta base excess = -3.35 +/- 3.06 mmol/L). The frequency of AEs after using prophylactic administration of sodium bicarbonate was lower in comparison with the frequency of AEs before using prophylactic administration of sodium bicarbonate (2.0% vs. 4.8%; p < 0.001). CONCLUSION: A decrease of serum pH and bicarbonate appeared in patients after PEs when albumin was used as replacement fluid; it was corrected partially with prophylactic administration of sodium bicarbonate, and it was associated with fewer AEs. PMID- 26267517 TI - Activating Mutations in PIK3CA Lead to Widespread Modulation of the Tyrosine Phosphoproteome. AB - The human oncogene PIK3CA is frequently mutated in human cancers. Two hotspot mutations in PIK3CA, E545K and H1047R, have been shown to regulate widespread signaling events downstream of AKT, leading to increased cell proliferation, growth, survival, and motility. We used quantitative mass spectrometry to profile the global phosphotyrosine proteome of isogenic knock-in cell lines containing these activating mutations, where we identified 824 unique phosphopeptides. Although it is well understood that these mutations result in hyperactivation of the serine/threonine kinase AKT, we found a surprisingly widespread modulation of tyrosine phosphorylation levels of proteins in the mutant cells. In the tyrosine kinome alone, 29 tyrosine kinases were altered in their phosphorylation status. Many of the regulated phosphosites that we identified were located in the kinase domain or the canonical activation sites, indicating that these kinases and their downstream signaling pathways were activated. Our study demonstrates that there is frequent and unexpected cross-talk that occurs between tyrosine signaling pathways and serine/threonine signaling pathways activated by the canonical PI3K AKT axis. PMID- 26267519 TI - The inhibitory effect of vitamin K on RANKL-induced osteoclast differentiation and bone resorption. AB - To further understand the correlation between vitamin K and bone metabolism, the effects of vitamins K1, menaquinone-4 (MK-4), and menaquinone-7 (MK-7) on RANKL induced osteoclast differentiation and bone resorption were comparatively investigated. Vitamin K2 groups (MK-4 and MK-7) were found to significantly inhibit RANKL-medicated osteoclast cell formation of bone marrow macrophages (BMMs) in a dose-dependent manner, without any evidence of cytotoxicity. The mRNA expression of specific osteoclast differentiation markers, such as c-Fos, NFATc1, OSCAR, and TRAP, as well as NFATc1 protein expression and TRAP activity in RANKL treated BMMs were inhibited by vitamin K2, although MK-4 exhibited a significantly greater efficiency compared to MK-7. In contrast, the same dose of vitamin K1 had no inhibitory effect on RANKL-induced osteoclast cell formation, but increased the expression of major osteoclastogenic genes. Interestingly, vitamins K1, MK-4 and MK-7 all strongly inhibited osteoclastic bone resorption (p < 0.01) in a dose dependent manner. These results suggest that vitamins K1, MK-4 and MK-7 have anti-osteoporotic properties, while their regulation effects on osteoclastogenesis are somewhat different. PMID- 26267520 TI - Clinical feasibility of a myocardial signal intensity threshold-based semi automated cardiac magnetic resonance segmentation method. AB - OBJECTIVES: To assess the accuracy and efficiency of a threshold-based, semi automated cardiac MRI segmentation algorithm in comparison with conventional contour-based segmentation and aortic flow measurements. METHODS: Short-axis cine images of 148 patients (55 +/- 18 years, 81 men) were used to evaluate left ventricular (LV) volumes and mass (LVM) using conventional and threshold-based segmentations. Phase-contrast images were used to independently measure stroke volume (SV). LV parameters were evaluated by two independent readers. RESULTS: Evaluation times using the conventional and threshold-based methods were 8.4 +/- 1.9 and 4.2 +/- 1.3 min, respectively (P < 0.0001). LV parameters measured by the conventional and threshold-based methods, respectively, were end-diastolic volume (EDV) 146 +/- 59 and 134 +/- 53 ml; end-systolic volume (ESV) 64 +/- 47 and 59 +/ 46 ml; SV 82 +/- 29 and 74 +/- 28 ml (flow-based 74 +/- 30 ml); ejection fraction (EF) 59 +/- 16 and 58 +/- 17%; and LVM 141 +/- 55 and 159 +/- 58 g. Significant differences between the conventional and threshold-based methods were observed in EDV, ESV, and LVM mesurements; SV from threshold-based and flow-based measurements were in agreement (P > 0.05) but were significantly different from conventional analysis (P < 0.05). Excellent inter-observer agreement was observed. CONCLUSIONS: Threshold-based LV segmentation provides improved accuracy and faster assessment compared to conventional contour-based methods. KEY POINTS: * Threshold-based left ventricular segmentation provides time-efficient assessment of left ventricular parameters * The threshold-based method can discriminate between blood and papillary muscles * This method provides improved accuracy compared to aortic flow measurements as a reference. PMID- 26267521 TI - Silver Enhancement for Transmission Electron Microscopy Imaging of Antibody Fragment-Gold Nanoparticles Conjugates Immobilized on Ordered Mesoporous Silica. AB - Ordered mesoporous silica (OMS) materials are receiving great attention as possible carriers for valuable but unstable drugs as, for example, therapeutic proteins. A key issue is to prove that the therapeutic protein is effectively able to penetrate the pores of OMS during the adsorption step. Here, we immobilized an antibody fragment [F(ab')GAMIgG] conjugated with ultrasmall gold nanoparticles (GNPs) onto amino-functionalized SBA-15 (SBA-NH2) mesoporous silica. The aim of this work is the visualization of the location of the conjugates adsorbed onto SBA-NH2 with transmission electron microscopy (TEM). Because of the ultrasmall size of GNPs (<1 nm), we use the silver enhancement procedure to amplify their size. In this procedure, ultrathin sections of conjugate-loaded SBA-NH2 particles are prepared by a ultramicrotome sectioning technique. The ultrasmall GNPs located on the top side of the 70-90 nm thick slices act as microcrystallization nucleation sites for the deposition of reduced metallic silver. Consequently, the ultrasmall GNPs increase their size. This allows for the direct imaging of the conjugates adsorbed. We clearly localize the F(ab')GAMIgG-GNPs conjugates either on the external surface of the particles or inside the mesopores of SBA-NH2 through TEM. PMID- 26267522 TI - Nonnutritive Sweeteners in Breast Milk. AB - Nonnutritive sweeteners (NNS), including saccharin, sucralose, aspartame, and acesulfame-potassium, are commonly consumed in the general population, and all except for saccharin are considered safe for use during pregnancy and lactation. Sucralose (Splenda) currently holds the majority of the NNS market share and is often combined with acesulfame-potassium in a wide variety of foods and beverages. To date, saccharin is the only NNS reported to be found in human breast milk after maternal consumption, while there is no apparent information on the other NNS. Breast milk samples were collected from 20 lactating volunteers, irrespective of their habitual NNS intake. Saccharin, sucralose, and acesulfame potassium were present in 65% of participants' milk samples, whereas aspartame was not detected. These data indicate that NNS are frequently ingested by nursing infants, and thus prospective clinical studies are necessary to determine whether early NNS exposure via breast milk may have clinical implications. PMID- 26267523 TI - The impact of comorbid chronic conditions on quality of life in type 2 diabetes patients. AB - OBJECTIVE: To study the prevalence, impact and dose-response relationship of comorbid chronic conditions on quality of life of type 2 diabetes patients. RESEARCH DESIGN AND METHODS: Cross-sectional data of 1676 type 2 diabetes patients, aged 31-96 years, and treated in primary care, were analyzed. Quality of life (QoL) was measured using the mental component summary (MCS) and the physical component summary (PCS) scores of the Short Form-12. Diagnosis of type 2 diabetes was obtained from medical records and comorbidities from self-reports. RESULTS: Only 361 (21.5%) of the patients reported no comorbidities. Diabetes patients with comorbidities showed significantly lower mean difference in PCS [ 8.5; 95% confidence interval (CI) -9.8 to -7.3] and MCS scores (-1.9; 95% CI -3.0 to -0.9), compared to diabetes patients without. Additional adjustments did not substantially change these associations. Both MCS and PCS scores decrease significantly with the number of comorbid conditions, yet most pronounced regarding physical QoL. Comorbidities that reduced physical QoL most significantly were retinopathy, heart diseases, atherosclerosis in abdomen or legs, lung diseases, incontinence, back, neck and shoulder disorder, osteoarthritis and chronic rheumatoid arthritis, using the backwards stepwise regression procedure. CONCLUSION: Comorbidities are highly prevalent among type 2 diabetes patients and have a negative impact on the patient's QoL. A strong dose response relationship between comorbidities and physical QoL was found. Reduced physical QoL is mainly determined by musculoskeletal and cardiovascular disorders. PMID- 26267524 TI - Development of an item bank for computerized adaptive test (CAT) measurement of pain. AB - PURPOSE: Patient-reported outcomes should ideally be adapted to the individual patient while maintaining comparability of scores across patients. This is achievable using computerized adaptive testing (CAT). The aim here was to develop an item bank for CAT measurement of the pain domain as measured by the EORTC QLQ C30 questionnaire. METHODS: The development process consisted of four steps: (1) literature search, (2) formulation of new items and expert evaluations, (3) pretesting and (4) field-testing and psychometric analyses for the final selection of items. RESULTS: In step 1, we identified 337 pain items from the literature. Twenty-nine new items fitting the QLQ-C30 item style were formulated in step 2 that were reduced to 26 items by expert evaluations. Based on interviews with 31 patients from Denmark, France and the UK, the list was further reduced to 21 items in step 3. In phase 4, responses were obtained from 1103 cancer patients from five countries. Psychometric evaluations showed that 16 items could be retained in a unidimensional item bank. Evaluations indicated that use of the CAT measure may reduce sample size requirements with 15-25% compared to using the QLQ-C30 pain scale. CONCLUSIONS: We have established an item bank of 16 items suitable for CAT measurement of pain. While being backward compatible with the QLQ-C30, the new item bank will significantly improve measurement precision of pain. We recommend initiating CAT measurement by screening for pain using the two original QLQ-C30 pain items. The EORTC pain CAT is currently available for "experimental" purposes. PMID- 26267525 TI - LEUKEMIC OPTIC NERVE INFILTRATION IN A PATIENT WITH ACUTE LYMPHOBLASTIC LEUKEMIA. AB - PURPOSE: To describe the clinical presentation and imaging features of a patient with acute lymphoblastic leukemia that was complicated by optic nerve leukemic infiltration. METHODS: A 36-year-old man with history of acute lymphoblastic leukemia on treatment presented with decreased vision and optic nerve leukemic infiltrates. RESULTS: At presentation, ocular examination revealed decreased visual acuity at hand movement close to face in his right eye and 20/120 in his left eye. Fundus examination showed a pale optic disk with blurred margins and multiple flame-shaped and dot and blot retinal hemorrhages in his right eye and disk edema with whitish leukemic infiltrates over it with few dot and blot retinal hemorrhages in his left eye. The patient was referred to the treating oncologist, and curative orbital radiotherapy was administered. Vision improved dramatically to 20/40 in the right eye and to 20/20 in the left eye. He again reported with complaints of blurring of vision in the left eye after 1 month. Visual acuity was 20/20, but fundus revealed severe disk edema with whitish leukemic infiltrates. We diagnosed as relapse of leukemic optic nerve infiltration and referred to the treating oncologist for further management. CONCLUSION: Isolated optic nerve relapse of leukemic infiltration is of paramount importance to early diagnosis, as vision can be saved if treatment is initiated promptly. PMID- 26267526 TI - DEVELOPMENT OF EPSTEIN-BARR VIRUS UVEITIS AFTER REMISSION OF PRIMARY VITREORETINAL LYMPHOMA. AB - PURPOSE: To describe a case of Epstein-Barr virus (EBV) uveitis that occurred after the treatment and remission of primary vitreoretinal lymphoma (PVRL). METHODS: Descriptive case report. Complete ophthalmologic evaluation, cytology, polymerase chain reaction, cytokine analysis of aqueous humor, and diagnostic vitrectomy were performed. RESULTS: A 66-year-old Caucasian woman developed uveitis in the same eye 20 months after remission of PVRL. Empiric chemotherapy failed to treat the suspected PVRL recurrence, and aqueous humor cytology showed an absence of malignant cells. Qualitative polymerase chain reaction of aqueous humor confirmed the presence of EBV. Treatment for EBV resulted in remission of the uveitis. CONCLUSION: The authors describe a rare case of EBV uveitis that was preceded by PVRL. It is important to consider EBV in cases where suspected recurrence of PVRL does not respond to appropriate treatment. PMID- 26267527 TI - AN UNUSUAL PRESENTATION OF CHOROIDAL SARCOIDOSIS AND ITS MULTIMODAL IMAGING. AB - PURPOSE: The purpose of this study was to report a case of a Filipino woman with a history of breast cancer who presented with unilateral choroidal infiltration, which led to the diagnosis of sarcoidosis. METHODS: Case report and literature review. RESULTS: A 64-year-old Filipino woman with a history of breast cancer presented with unilateral choroidal nodules. Her blood tests were negative for common causes of choroidal infiltration (angiotensin-converting enzyme, lysozyme, Treponema pallidum particle agglutination), and Mantoux skin test and a chest x ray were negative. Her diagnosis could only be made by biopsy of the two hypermetabolic paratracheal nodes seen on the positron emission tomography computed tomography. CONCLUSION: Choroidal infiltration may be the presenting feature of sarcoidosis even in ethnicities known to have very low incidence of the disease. If the chest x-ray is negative and the clinical suspicion warrants it, a CT or positron emission tomography-computed tomography of the thorax may be helpful in identifying nonhilar mediastinal lymphadenopathy. As in our case, fine needle aspiration biopsy of these nodes may lead to confirmation of the diagnosis. PMID- 26267528 TI - PIPPing on AKT1: How Many Phosphatases Does It Take to Turn off PI3K? AB - In this issue of Cancer Cell, Ooms and colleagues show that the lipid phosphatase PIPP/INPP5J, frequently inactivated in triple-negative breast cancers, functions as a tumor suppressor by specifically modulating the activity of AKT1 in the context of oncogenic PI3K signaling, leading to inhibition of metastatic dissemination. PMID- 26267529 TI - A Kinase Divided. AB - In this issue of Cancer Cell, Herrero and colleagues identify an anti-tumorigenic small molecule that blocks ERK dimerization, but neither its catalytic activity nor its phosphorylation by MEK. These findings demonstrate that targeting protein dimerization could be a therapeutic avenue for inhibiting kinase signaling pathways associated with lower drug resistance. PMID- 26267530 TI - ROR1C Regulates Differentiation of Myeloid-Derived Suppressor Cells. AB - Myeloid-derived suppressor cells (MDSCs) play a major role in cancer. MDSC expansion is closely associated with tumor progression, but molecular mechanisms of this expansion remain poorly understood. In this issue of Cancer Cell, Strauss and colleagues describe the roles of the nuclear receptor ROR1C in the regulation of MDSC differentiation and expansion. PMID- 26267531 TI - Tumor Heterogeneity: Focus on the Leaves, the Trees, or the Forest? AB - Molecular studies of intra-tumor heterogeneity (ITH) are revealing a large amount of DNA-based variation in many individual tumors. In a recent publication by Yates and colleagues, the ITH of breast tumors was examined and shown to have important implications for the development of resistant disease, metastasis, and clinical sequencing efforts. PMID- 26267532 TI - Intercepting Cancer Communiques: Exosomes as Heralds of Malignancy. AB - In clinical oncology, detecting and treating disease as early as possible is the brass ring to be grasped. Does a new test based on circulating exosomes bring it closer for patients with pancreas cancer? PMID- 26267533 TI - The Inositol Polyphosphate 5-Phosphatase PIPP Regulates AKT1-Dependent Breast Cancer Growth and Metastasis. AB - Metastasis is the major cause of breast cancer mortality. Phosphoinositide 3 kinase (PI3K) generated PtdIns(3,4,5)P3 activates AKT, which promotes breast cancer cell proliferation and regulates migration. To date, none of the inositol polyphosphate 5-phosphatases that inhibit PI3K/AKT signaling have been reported as tumor suppressors in breast cancer. Here, we show depletion of the inositol polyphosphate 5-phosphatase PIPP (INPP5J) increases breast cancer cell transformation, but reduces cell migration and invasion. Pipp ablation accelerates oncogene-driven breast cancer tumor growth in vivo, but paradoxically reduces metastasis by regulating AKT1-dependent tumor cell migration. PIPP mRNA expression is reduced in human ER-negative breast cancers associated with reduced long-term outcome. Collectively, our findings identify PIPP as a suppressor of oncogenic PI3K/AKT signaling in breast cancer. PMID- 26267534 TI - Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes. AB - Nearly 50% of human malignancies exhibit unregulated RAS-ERK signaling; inhibiting it is a valid strategy for antineoplastic intervention. Upon activation, ERK dimerize, which is essential for ERK extranuclear, but not for nuclear, signaling. Here, we describe a small molecule inhibitor for ERK dimerization that, without affecting ERK phosphorylation, forestalls tumorigenesis driven by RAS-ERK pathway oncogenes. This compound is unaffected by resistance mechanisms that hamper classical RAS-ERK pathway inhibitors. Thus, ERK dimerization inhibitors provide the proof of principle for two understudied concepts in cancer therapy: (1) the blockade of sub-localization-specific sub signals, rather than total signals, as a means of impeding oncogenic RAS-ERK signaling and (2) targeting regulatory protein-protein interactions, rather than catalytic activities, as an approach for producing effective antitumor agents. PMID- 26267536 TI - Long-Pentraxin 3 Derivative as a Small-Molecule FGF Trap for Cancer Therapy. AB - The fibroblast growth factor (FGF)/FGF receptor (FGFR) system plays a crucial role in cancer by affecting tumor growth, angiogenesis, drug resistance, and escape from anti-angiogenic anti-vascular endothelial growth factor therapy. The soluble pattern recognition receptor long-pentraxin 3 (PTX3) acts as a multi-FGF antagonist. Here we demonstrate that human PTX3 overexpression in transgenic mice driven by the Tie2 promoter inhibits tumor growth, angiogenesis, and metastasis in heterotopic, orthotopic, and autochthonous FGF-dependent tumor models. Using pharmacophore modeling of the interaction of a minimal PTX3-derived FGF-binding pentapeptide with FGF2, we identified a small-molecule chemical (NSC12) that acts as an extracellular FGF trap with significant implications in cancer therapy. PMID- 26267535 TI - ERK2-Dependent Phosphorylation of CSN6 Is Critical in Colorectal Cancer Development. AB - Biomarkers for predicting prognosis are critical to treating colorectal cancer (CRC) patients. We found that CSN6, a subunit of COP9 signalosome, is overexpressed in CRC samples and that CSN6 overexpression is correlated with poor patient survival. Mechanistic studies revealed that CSN6 is deregulated by epidermal growth factor receptor (EGFR) signaling, in which ERK2 binds directly to CSN6 Leu163/Val165 and phosphorylates CSN6 at Ser148. Furthermore, CSN6 regulated beta-Trcp and stabilized beta-catenin expression by blocking the ubiquitin-proteasome pathway, thereby promoting CRC development. High CSN6 expression was positively correlated with ERK2 activation and beta-catenin overexpression in CRC samples, and inhibiting CSN6 stability with cetuximab reduced colon cancer growth. Taken together, our study's findings indicate that the deregulation of beta-catenin by ERK2-activated CSN6 is important for CRC development. PMID- 26267538 TI - RORC1 Regulates Tumor-Promoting "Emergency" Granulo-Monocytopoiesis. AB - Cancer-driven granulo-monocytopoiesis stimulates expansion of tumor promoting myeloid populations, mostly myeloid-derived suppressor cells (MDSCs) and tumor associated macrophages (TAMs). We identified subsets of MDSCs and TAMs based on the expression of retinoic-acid-related orphan receptor (RORC1/RORgamma) in human and mouse tumor bearers. RORC1 orchestrates myelopoiesis by suppressing negative (Socs3 and Bcl3) and promoting positive (C/EBPbeta) regulators of granulopoiesis, as well as the key transcriptional mediators of myeloid progenitor commitment and differentiation to the monocytic/macrophage lineage (IRF8 and PU.1). RORC1 supported tumor-promoting innate immunity by protecting MDSCs from apoptosis, mediating TAM differentiation and M2 polarization, and limiting tumor infiltration by mature neutrophils. Accordingly, ablation of RORC1 in the hematopoietic compartment prevented cancer-driven myelopoiesis, resulting in inhibition of tumor growth and metastasis. PMID- 26267537 TI - Characterization of a Steroid Receptor Coactivator Small Molecule Stimulator that Overstimulates Cancer Cells and Leads to Cell Stress and Death. AB - By integrating growth pathways on which cancer cells rely, steroid receptor coactivators (SRC-1, SRC-2, and SRC-3) represent emerging targets in cancer therapeutics. High-throughput screening for SRC small molecule inhibitors (SMIs) uncovered MCB-613 as a potent SRC small molecule "stimulator" (SMS). We demonstrate that MCB-613 can super-stimulate SRCs' transcriptional activity. Further investigation revealed that MCB-613 increases SRCs' interactions with other coactivators and markedly induces ER stress coupled to the generation of reactive oxygen species (ROS). Because cancer cells overexpress SRCs and rely on them for growth, we show that we can exploit MCB-613 to selectively induce excessive stress in cancer cells. This suggests that over-stimulating the SRC oncogenic program can be an effective strategy to kill cancer cells. PMID- 26267539 TI - Iodine(III)-Mediated Diazidation and Azido-oxyamination of Enamides. AB - In this study we demonstrate that the combination of bis(tert butylcarbonyloxy)iodobenzene and lithium azide in acetonitrile allows the diazidation of various enamide substrates. The azido-oxyamination of the same substrates can be carried out in the presence of 2,2,6,6-tetramethylpiperidine N oxide (TEMPO). Control experiments strongly suggest that this latter process occurs through a shift in nature of the in situ generated electrophilic species from a radical to a cation. Finally, the versatility of the novel compounds synthesized was also assessed by running various selective reactions on them. PMID- 26267540 TI - The Feasibility and Outcome of Oro-esophageal Tube Feeding in Patients with Various Etiologies. AB - The oro-esophageal tube (OE tube) is widely used in dysphagia patients although its success rate for transition to oral feeding is reported only in stroke patients. The aim of this study was to evaluate the feasibility and outcome of OE tube feeding for patients with dysphagia resulting from various etiologies. The authors reviewed the medical records of 1995 dysphagic patients that had undergone videofluoroscopic swallowing study (VFSS) in a tertiary hospital from April 2002 through December 2009. Of these, 97 patients were recommended to use OE tube feeding based on the VFSS findings. Follow-up VFSS were performed on 54 patients. The mean duration of tube use at the time of follow-up VFSS was 274 days. We evaluated clinical information including age, sex, diet, etiology of dysphagia, location of lesions, duration of intervention, and complications of OE tube feeding. Initially, all 54 patients were fed using the OE tube. After their last follow-up evaluation, 19 patients (35.2 %) resumed full oral feeding without the OE tube, 12 patients (22.2 %) used partial OE tube feeding, and 23 patients (42.6 %) continued OE tube feeding only. Full oral feeding was achieved again most often in brain tumor, stroke, and head and neck cancer patients (54.5, 27.3, and 20.0 %, respectively). Mild adverse events, such as blood-tinged sputum, nausea, dyspepsia, and regurgitation of food, were reported in 4 patients. OE tube feeding is a feasible feeding method also in conditions other than stroke such as brain tumors, and head and neck cancers. PMID- 26267542 TI - Phylogenetic, Morphological, and Pathogenic Characterization of Alternaria Species Associated with Fruit Rot of Blueberry in California. AB - Fruit rot caused by Alternaria spp. is one of the most important factors affecting the postharvest quality and shelf life of blueberry fruit. The aims of this study were to characterize Alternaria isolates using morphological and molecular approaches and test their pathogenicity to blueberry fruit. Alternaria spp. isolates were collected from decayed blueberry fruit in the Central Valley of California during 2012 and 2013. In total, 283 isolates were obtained and five species of Alternaria, including Alternaria alternata, A. tenuissima, A. arborescens, A. infectoria, and A. rosae, were identified based on DNA sequences of the plasma membrane ATPase, Alt a1 and Calmodulin gene regions in combination with morphological characters of the culture and sporulation. Of the 283 isolates, 61.5% were identified as A. alternata, 32.9% were A. arborescens, 5.0% were A. tenuissima, and only one isolate of A. infectoria and one isolate of A. rosae were found. These fungi were able to grow at temperatures from 0 to 35 degrees C, and mycelial growth was arrested at 40 degrees C. Optimal radial growth occurred between 20 to 30 degrees C. Pathogenicity tests showed that all five Alternaria spp. were pathogenic on blueberry fruit at 0, 4, and 20 degrees C, with A. alternata, A. arborescens, and A. tenuissima being the most virulent species, followed by A. infectoria and A. rosae. Previously A. tenuissima has been reported to be the primary cause of Alternaria fruit rot of blueberry worldwide. Our results indicated that the species composition of Alternaria responsible for Alternaria fruit rot in blueberry can be dependent on geographical region. A. alternata, A. arborescens, A. infectoria, and A. rosae are reported for the first time on blueberry in California. This is also the first report of A. infectoria and A. rosae infecting blueberry fruit. PMID- 26267541 TI - Evaluation of swallowing function after supracricoid laryngectomy as a primary or salvage procedure. AB - The primary functional issues following conservative therapy for advanced laryngeal cancer concern swallowing. Here, we evaluated the recovery of swallowing after supracricoid partial laryngectomy (SCL) in patients with primary or recurrent laryngeal cancer. We evaluated the swallowing recovery in 27 SCL patients through oropharyngoesophageal scintigraphy, and we evaluated their quality of life using EORTC questionnaires. Four patients underwent total laryngectomy during follow-up. Patients who retained their larynges were able to feed without nutritional support and without tracheostoma. The only significantly different parameter between the primary and salvage cases was the time elapsed to the removal of nasogastric/PEG tubes, which was longer in salvage cases. SCL has been demonstrated as a valuable option for primary and recurrent laryngeal cancer patients. The present data demonstrate good functional results, particularly in terms of swallowing after previous treatments and in primary settings. The combination of oropharyngoesophageal scintigraphy and questionnaires appears to be an adequate, standardizable approach to assessing swallowing function after SCL. PMID- 26267543 TI - Inheritance of Resistance to Powdery Mildew Race 1W in Watermelon. AB - Powdery mildew caused by Podosphaera xanthii is a major disease of watermelon in Israel. In this study, 291 accessions of Citrullus spp. were evaluated for resistance against P. xanthii race 1W. Only eight accessions exhibited high level of resistance. Inheritance of resistance against P. xanthii race 1W was studied by crossing three resistant accession of Citrullus lanatus var. citroides BIU 119, PI 189225, or PI 482312 with the susceptible cultivar 'Malali' or 'Sugar Baby'. Parents, F1, F2, and back cross progenies were evaluated for resistance in growth chambers at the cotyledon stage and the 4-leaf stage and in the field, at the 15-leaf stage. Resistance at the cotyledon stage was controlled by a single, partially dominant gene, whereas at the 4-leaf stage or the 15-leaf stage resistance was controlled by three complimentary, partially dominant genes. Crosses made among these resistant accessions revealed that BIU 119 and PI 189225 carry the same genes for resistance, whereas PI 482312 shares two out of three genes with both BIU 119 and PI 189225. A breeding line with high resistance level and good fruit qualities was developed from BIU 119 * HA5500. PMID- 26267544 TI - The Future of Imaging. PMID- 26267545 TI - Invisalign treatment of Class III malocclusion with lower-incisor extraction. PMID- 26267546 TI - The Herbst appliance 32 years after treatment. PMID- 26267547 TI - A customized appliance for molar uprighting and space regaining. PMID- 26267548 TI - Coordinated logopedic and lingual-orthodontic treatment of an open-bite case. PMID- 26267549 TI - Management of maxillary central incisor fenestration with a 2 x 2 appliance. PMID- 26267550 TI - Treatment of pseudo-class III malocclusion with a modified reverse twin block and fixed appliances. PMID- 26267551 TI - Clinical value of pulse wave velocity: a promising marker for arterial stiffness. PMID- 26267552 TI - In vitro and in vivo corrosion of the novel magnesium alloy Mg-La-Nd-Zr: influence of the measurement technique and in vivo implant location. AB - For the evaluation of new magnesium-based alloys, many different in vitro and in vivo methods are used. It was the aim of the current study to perform in vitro and in vivo corrosion studies of the new alloy Mg-La-Nd-Zr for its evaluation as a promising new degradable material and to compare commonly used evaluation methods. Die casted and subsequent extruded cylindrical pins (O1.5 mm; length 7 mm, [Formula: see text]) were implanted subcutaneously ([Formula: see text]), intramuscular ([Formula: see text]) and intramedullary ([Formula: see text]) in female Lewis rats with a postoperative follow up of 8 weeks; subsequent MU computed tomographical analyses (XTremeCT and MUCT80) were performed as well as weight analysis prior to and after implantation. Cubes (5 mm * 4 mm * 4 mm; surface area, 1.12 cm(2); [Formula: see text]) were used for in vitro corrosion (HBSS and RPMI 1640 + 10% FBS medium) and cytocompatibility studies (L929 cells). First of all it could be stated that implant location strongly influences the in vivo corrosion rate. In particular, intramedullary implanted pins corroded faster than pins in a subcutaneous or intramuscular environment. Considering the different evaluation methods, the calculated ex vivo MUCT-based corrosion rates resulted in comparable values to the corrosion rates calculated by the weight loss method, especially after chromatic acid treatment of the explanted pins. The in vitro methods used tend to show similar corrosion rates compared to in vivo corrosion, especially when a RPMI medium was used, and therefore are suitable to predict corrosion trends prior to in vivo studies. Regarding cytocompatibility, the novel magnesium alloy Mg-La-Nd-Zr showed sufficient cell viability and therefore can be considered as a promising alloy for further applications. PMID- 26267553 TI - Modulation and the Underlying Mechanism of T Cells in Thymus of Mice by Oral Administration of Sodium Fluoride. AB - The underlying mechanism of thymic T cell regulation has been a hot topic of research in recent years. Fluoride is toxic at high concentrations and fluoride toxicity to thymic T cells was assessed in our study. To explore T cell responses to excess fluoride, different concentrations of fluoride were uptake by mice for 6 weeks. The expression of genes, including Foxn1, Cbx4, DLL4, and IL-7 gene, associated with the development and differentiation of T cells in thymic epithelial cells(TECs) was lower in the experimental groups than that in the control group. The percentages of CD4(+) and CD8(+) T cells that decreased with the fluoride administration were confirmed by flow cytometry. The mRNA levels of immunoregulatory cytokines IL-2 and IL-10, which participate in T cell proliferation, also declined in the experimental groups as compared with the control group. Expression of the T cell function-related genes CD2, PTPRC, CD69, and CD101, which are involved in thymic function in mice, decreased with the fluoride administration. Our findings suggest that the administration of high concentrations of fluoride to mice induces a decrease in CD4(+) and CD8(+) thymus T cells by harming TECs leading to the dysfunction of the thymus by altering the expression of T cell function-related genes and immunoregulatory cytokine production. PMID- 26267554 TI - Prosody and language comprehension. AB - This review provides a summary of the most recent advances on the study of how prosody is used during language comprehension. Prosody is characterized as an abstract structure composed of discrete tonal elements aligned with the segmental composition of the sentence organized in constituents of increasing size, and this structure is influenced by the phonological, syntactic, and informational structures of the sentence. Here, we discuss evidence that listeners are affected by prosody when establishing those linguistic structures. Prosody has been shown to influence the segmentation of the utterance into syllables and words, and, in some cases, whether a syllable or word is judged to be present or not. The literature on how prosody informs the structural relationship between words and phrases is also discussed, contrasting views that assume a direct (albeit probabilistic) link between syntax and prosody with those that posit a complex interface between syntax and prosodic structure. Finally, the role of prosody in conveying important aspects pertaining to the sentence's information structure (i.e., which parts of the sentence's meaning are highlighted and brought forward to the discourse, which ones are presupposed and left in the background, which attitudes are being conveyed about the concepts or propositional content) has long been recognized. Current research focuses on which prosodic elements contribute to marking the dimensions (or semantic primitives) of the information structure. PMID- 26267556 TI - Cadmium potentiates toxicity of cypermethrin in zebrafish. AB - Co-occurrence of pesticides such as synthetic pyrethroids and metals in aquatic ecosystems raises concerns over their combined ecological effects. Cypermethrin, 1 of the top 5 synthetic pyrethroids in use, has been extensively detected in surface water. Cadmium (Cd) has been recognized as 1 of the most toxic metals and is a common contaminant in the aquatic system. However, little information is available regarding their joint toxicity. In the present study, combined toxicity of cypermethrin and Cd and the underlying mechanisms were investigated. Zebrafish embryos and adults were exposed to the individual contaminant or binary mixtures. Co-exposure to cypermethrin and Cd produced synergistic effects on the occurrence of crooked body, pericardial edema, and noninflation of swim bladder. The addition of Cd significantly potentiated cypermethrin-induced spasms and caused more oxidative stress in zebrafish larvae. Cypermethrin-mediated induction of transcription levels and catalytic activities of cytochrome P450 (CYP) enzyme were significantly down-regulated by Cd in both zebrafish larvae and adults. Chemical analytical data showed that in vitro elimination of cypermethrin by CYP1A1 was inhibited by Cd. The addition of Cd caused an elevation of in vivo cypermethrin residue levels in the mixture-exposed adult zebrafish. These results suggest that the enhanced toxicity of cypermethrin in the presence of Cd results from the inhibitory effects of Cd on CYP-mediated biotransformation of this pesticide. The authors' findings provide a deeper understanding of the mechanistic basis accounting for the joint toxicity of cypermethrin and Cd. PMID- 26267557 TI - Quantum dot/methylene blue FRET mediated NIR fluorescent nanomicelles with large Stokes shift for bioimaging. AB - Here we present a novel large Stokes shifting NIR fluorescent nanomicelle through the encapsulation of a quantum dot/methylene blue FRET pair, which is employed as an excellent contrast reagent for NIR fluorescence bioimaging. PMID- 26267558 TI - Synthesis and Optical Properties of PbSe Nanorods with Controlled Diameter and Length. AB - The synthesis of PbSe nanorods with low branching (<1%), high aspect ratios (up to ~16), and controlled lengths and diameters was demonstrated via the removal of water and oleic acid from the synthesis precursors. It was determined that the proper combination of reaction time and temperature allows for the control of PbSe nanorod length and diameter and therefore control over their electronic states, as probed through absorbance and photoluminescence measurements. Similar to PbSe nanowires, nanorods display higher Stokes shifts than for spherical nanocrystals due to intrananorod diameter fluctuations. PMID- 26267559 TI - Tailoring the strain in Si nano-structures for defect-free epitaxial Ge over growth. AB - We investigate the structural properties and strain state of Ge nano-structures selectively grown on Si pillars of about 60 nm diameter with different SiGe buffer layers. A matrix of TEOS SiO2 surrounding the Si nano-pillars causes a tensile strain in the top part at the growth temperature of the buffer that reduces the misfit and supports defect-free initial growth. Elastic relaxation plays the dominant role in the further increase of the buffer thickness and subsequent Ge deposition. This method leads to Ge nanostructures on Si that are free from misfit dislocations and other structural defects, which is not the case for direct Ge deposition on these pillar structures. The Ge content of the SiGe buffer is thereby not a critical parameter; it may vary over a relatively wide range. PMID- 26267560 TI - Assessment of Head Shape by Craniofacial Teams: Structuring Practice Parameters to Optimize Efficiency. AB - INTRODUCTION: Since the initiation of the "Back to Sleep Campaign" by the American Academy of Pediatrics in 1992, the incidence of referrals for positional plagiocephaly has increased by 600%. Although patients with positional plagiocephaly rarely require operative intervention, they often do require treatment with cranial molding helmets or positioning changes. The increased volume of patients makes the task of separating cases of craniosynostosis from positional head shape problems more difficult. The authors sought to determine how providers are handling this increased workload of head shape abnormality patients, especially with respect to the largest practices. MATERIALS AND METHODS: An electronic survey was created and distributed to members of the American Society of Maxillofacial Surgeons and the American Cleft Palate Association (ACPA). Practices were categorized by head shape patient volume as low (<4 new patients/month), medium (5-20 new patients/month), and high (>21 new patients/month). A Pearson's chi test was used to determine characteristics that differed significantly with practice volume. RESULTS: Response rate was 6.6%, with 88 responses. Regarding head shape evaluation, 17.6% of practices used a laser scanner (portable or stationary), 35.3% used caliper anthropometric measurements, 28.5% used two-dimensional digital photography, and 9.4% used three dimensional digital photography. In high-volume centers, 80% had a dedicated head shape clinic (P < 0.0005), 33.3% used a stationary laser scanner (P = 0.023), and 53.3% used a licensed independent provider (LIP) such as a nurse practitioner or physician assistant in the initial evaluation of head shape abnormalities (P = 0.032). Although using a multidisciplinary clinic was not a significant difference amongst groups, the most common additional provider in multidisciplinary clinic was orthotics (68%). CONCLUSIONS: High-volume practices are significantly more likely to use LIPs, stationary laser scanners, and plain films, as well as organizing head shape abnormality patients into a dedicated clinic. PMID- 26267561 TI - Tracheal Resection With Primary Anastomosis. AB - The aim of our study was to present our retrospective experience in the single stage surgical reconstruction of 21 tracheal stenosis (TS) patients during the last 17 years, considering the characteristics of the treated stenosis, surgical procedures performed, and postoperative outcomes and complications. All demographic and clinical data were collected retrospectively. Chest and neck computed tomography (CT) scans were performed to assess the stenosis, including length, location, and glottic involvement. The stenotic area was evaluated endoscopically according to an adapted Myer and Cotton grading scale. The aetiology of the (TS) was intubation related in 18 patients and idiopathic in three patients. The duration of intubation was 13.00 +/- 6.83 days (range, 1 hour to 27 days). According to the Myers-Cotton classification, mean stage of stenosis for the study group was 3.33 +/- 0.66 (range, 2-4). Mean length of the stenosis was 2.05 +/- 0.80 (range, 1-3.5) cm. The mean number of stenotic segment involved was 3.67 +/- 1.24 (range, 2-6). Mean follow-up for the study group, excluding two patients who died in the postoperative period, was 57 (range, 12-326) months. Of the 19 patients who survived, postoperative decannulation was achieved in 16 patients (76.19%), and decannulation was not achieved in 3 patients (14.29%) who are still on a T-tube. Of the 16 patients who are decannulated successfully, additional procedures were applied in 9 patients. Segmental resection with primary anastomosis is an effective method and can be used as the first option in selected patients of (TS). PMID- 26267562 TI - Family of Crouzon Syndrome Represents the Evolution of the Frontofacial Monobloc Advancement Technique: From Immediate Movement to Monobloc Distraction to Monobloc Bipartition Distraction. AB - Crouzon syndrome (CS) is an autosomal dominant disorder characterized by premature fusion of cranial sutures, midface and supraorbital ridge retrusion, exorbitism, and in some clinical scenarios strabismus, parrot-beaked nose, short upper lip and hypertelorbitism. Treatment of CS is overlapped with the beginning of craniofacial surgery and is grounded on morphologic and functional objectives. The authors reported on the outcomes and complications of family members (mother and 2 siblings) with CS, who were operated on by different techniques of frontofacial advancement and have attained skeletal maturity. Operations were performed in different moments throughout the last 3 decades of craniofacial surgery history. A 10-year-old Crouzon progenitor underwent a monobloc osteotomy with acute advancement, using rigid fixation and bone grafting in the osteotomy sites. An 8-year-old Crouzon daughter underwent gradual lengthening of a monobloc segment, using an external, institutionally made distracter device. In addition, a 10-year-old Crouzon son underwent gradual lengthening of a monobloc segment associated to facial bipartition, using an internal distracter device. After 30 years, the mother presented a mild relapse on the orbit level, but her children had satisfactory stable outcomes. The family members with CS have undergone different modifications of the monobloc approach based on different chronological momentum, from acute monobloc advancement, to monobloc distraction, to monobloc facial bipartition distraction. PMID- 26267563 TI - Isolated Unilateral Frontosphenoidal Craniosynostosis: A Rare Cause of Anterior Plagiocephaly. AB - Isolated unilateral frontosphenoidal synostosis is a rare and often misdiagnosed cause of synostotic frontal plagiocephaly. It is important to distinguish the various synostotic causes of frontal plagiocephaly from deformational frontal plagiocephaly because operative intervention is required in synostotic plagiocephaly to avoid progressive deformity, whereas deformational plagiocephaly typically improves without surgery. This study reports a patient with a unique case of anterior plagiocephaly caused by left-sided frontosphenoidal craniosynostosis. The workup should include a thorough history and clinical examination followed by computed tomography scan with three-dimensional reconstruction. Frontosphenoidal synostosis should be suspected in the absence of a coronal synostosis in a child with anterior unilateral plagiocephaly and treated surgically. Good aesthetic and functional results occur with prompt diagnosis and early surgical correction. PMID- 26267564 TI - Periosteal Transposition Flap for Graft Coverage and Ridge Preservation in the Aesthetic Zone. AB - Implant treatment in esthetic zone has been challenging for a long time. To achieve the best results optimum amounts of alveolar bone and soft tissue especially attached gingiva is needed. We presented the use of inverted periosteal flap which is a periosteal transposition flap in an esthetic zone. This flap may play a significant role in ridge augmentation and socket preservation in the esthetic zone and could be considered as an alternative for other local flaps. This flap provides sufficient-soft tissue coverage and reduces the risk of dehiscence. PMID- 26267565 TI - Functional Sharing of the Upper Orbicularis Oris Muscle for the Reconstruction of the Lower Lip. AB - The lip reconstruction is a very controversial topic in plastic surgery and many flaps have been described for this purpose. Despite all of the interventions, some patients still have problems such as drooling and gingival show that decrease their quality of life. In this study, the authors report a patient whose lower lip was resected totally for squamous cell carcinoma. His lip was reconstructed with radial forearm flap and the patient was referred to our clinic with the aforementioned complaints. A portion of the orbicularis oris muscle of the upper lip was designed as a bipedicled flap, and it was transposed to the lower lip to make the initial flap functional. After the operation, the sphincteric function of the lip was better, and the problems as drooling and gingival show were absent. In conclusion, this flap can be a good option to make the initial nonfunctional flaps (such as radial forearm flap), functional in the aspect of lower lip reconstruction. It has a function, and it is concordant with the principle of "reconstructing like with like." The native muscle tissue of the upper lip can be transferred partially to maintain physiologic oral competency. PMID- 26267566 TI - Dental Extractions Management in Bernard-Soulier Syndrome. PMID- 26267567 TI - Bone Healing in the Surgical Treatment of Dentigerous Cysts in Critically Ill Patients. PMID- 26267568 TI - An Experimental Model Design for Photoaging. AB - Autologous adipose-derived stem cells have shown great promise in applications that treat photodamaged skin. Adipose-derived stem cells also have an antiwrinkle effect; consequently, they have become a topic of primary interest. Nude mice have been used extensively in studies of adipose-derived stem cells, human dermal fibroblasts, and other filler injections. However, a nude mouse model of photoaging has not yet been developed. Thus, we attempted to develop a nude mouse model of photoaging in this study. MATERIALS AND METHODS: Fourteen, 5-week-old female BALB/c nude mice were irradiated with ultraviolet-B rays, 6 times a week for 6 weeks. The minimum erythema dose was established before the mice underwent ultraviolet irradiation to minimize the inflammation of the irradiated skin and to determine the initial irradiation dosage. The mean sizes of the wrinkled areas of skin and the mean depths of the wrinkles were compared between the study groups using replica analysis. Skin biopsies were performed on the 6th and 10th weeks of the study. RESULTS: The mean sizes of the wrinkled areas of skin and the mean depths of the wrinkles increased significantly in the ultraviolet-B irradiated nude mice compared with the nonirradiated mice, and the thicknesses of the epidermis and dermis of the skin from the upper and lower back were significantly greater after ultraviolet-B irradiation up to the 6th week of treatment (P < 0.05). Furthermore, the ultraviolet-B-irradiated group demonstrated reduced collagen fiber levels. CONCLUSIONS: We have successfully developed a nude mouse model for research into photoaging, and these results indicate that the nude mouse is a suitable model for investigating the development of photoaging. PMID- 26267569 TI - Reconstruction of Complex Facial Defects Using Cervical Expanded Flap Prefabricated by Temporoparietal Fascia Flap. AB - Reconstruction of complex facial defects using cervical expanded flap prefabricated by temporoparietal fascia flap. BACKGROUND: Complex facial defects are required to restore not only function but also aesthetic appearance, so it is vital challenge for plastic surgeons. Skin grafts and traditional flap transfer cannot meet the reconstructive requirements of color and texture with recipient. The purpose of this sturdy is to create an expanded prefabricated temporoparietal fascia flap to repair complex facial defects. METHODS: Two patients suffered severe burns on the face underwent complex facial resurfacing with prefabricated cervical flap. The vasculature of prefabricated flap, including the superficial temporal vessel and surrounding fascia, was used as the vascular carrier. The temporoparietal fascia flap was sutured underneath the cervical subcutaneous tissue, and expansion was begun in postoperative 1 week. After 4 to 6 months of expansion, the expander was removed, facial scars were excised, and cervical prefabricated flap was elevated and transferred to repair the complex facial defects. RESULTS: Two complex facial defects were repaired successfully by prefabricated temporoparietal fascia flap, and prefabricated flaps survived completely. On account of donor site's skin was thinner and expanded too fast, 1 expanded skin flap was rupture during expansion, but necrosis was not occurred after the 2nd operation. Venous congestion was observed in 1 patient, but after dressing, flap necrosis was not happened. Donor site was closed primarily. Postoperative follow-up 6 months, the color, texture of prefabricated flap was well-matched with facial skin. CONCLUSION: This method of expanded prefabricated flap may provide a reliable solution to the complex facial resurfacing. PMID- 26267570 TI - Chondrosarcoma of the Laryngeal Thyroid Cartilage. AB - Chondrosarcoma of the larynx is a rare tumor, accounting for 0.07% to 2% of all laryngeal cancers. Nevertheless, it represents the most frequent nonepithelial neoplasm of the laryngeal region.Laryngeal chondrosarcomas are usually characterized by slow growth and low metastatic potential.The exact etiopathogenesis of chondrosarcoma is still debated. Diagnosis can be difficult given the slow rate of growth and nonspecific patient symptoms at presentation.Because of its rarity, literature about laryngeal chondrosarcoma is mainly made up of case reports and small case series.Therefore, it is important to add any information regarding this pathology.The aim of this article was to present and discuss a new case of chondrosarcoma located in the thyroid cartilage in a 63-year-old woman. PMID- 26267571 TI - Effects of Vertical Movement of the Anterior Nasal Spine on the Maxillary Stability After LeFort I Osteotomy for Pitch Correction. AB - Few reports have so far evaluated the maxillary stability after LeFort I osteotomy (L-1) for pitch correction. In the current study, the authors assessed the SN-PP (palatal plane) to evaluate the skeletal stability after osteotomy with clockwise or counter-clockwise rotation and investigated the effects of anterior nasal spine (ANS) and posterior nasal spine (PNS) movement on the stability of the SN-PP.The SN-PP and the positions of ANS, PNS, and point A were measured on lateral cephalograms before surgery (T1), immediately after surgery (T2), and more than 1 year after surgery (T3).All measured angle and points were stable in 4 cases of counter-clockwise rotation. In the 16 cases of clockwise rotation, T3 T2 of SN-PP, ANS, and point A was -2.05 degrees , -2.56 mm, and -1.64 mm, when the SN-PP increased more than 4 degrees after osteotomy. When the ANS moved downward more than 3 mm, the ANS and point A relapsed significantly by 2.75 and 2.31 mm, while the SN-PP relapsed 1.61 degrees more than 1 year after surgery.When the SN-PP increased by more than 4 degrees or the ANS moved downward by more than 3 mm, the authors suggest shifting the PNS upward instead of moving the ANS downward. PMID- 26267572 TI - Clinical Characteristics and Surgical Treatment of Intraorbital Foreign Bodies in a Tertiary Eye Center. AB - PURPOSE: Intraorbital foreign body is relatively rare and therefore is often misdiagnosed in clinical practice. The purpose of this report is to summarize the clinical features of intraorbital foreign bodies and their surgical management. METHODS: A retrospective study of clinical cases. Clinical manifestations, imaging findings, and surgical treatments in patients with intraorbital foreign bodies, who were seen at the Zhongshan Ophthalmic Center of Sun Yat-sen University between January 2002 and July 2013, were retrospectively reviewed. RESULTS: Of the 22 cases reviewed, 19 were men and 3 women with a mean age of 22.2 years. Patients <=14 years of age accounted for 45.5% of the cases. The right orbit was affected in 10 patients and the left in 12 patients. Organic intraorbital foreign bodies comprised 72.7% of the patients. Foreign body locations within the orbit were superior (40.9%), medial (27.3%), lateral (18.2%), and inferior (9.1%). Half of the patients presented with preoperative visual impairments and 45.5% with limited motility/strabismus and ptosis. Orbital imaging revealed that organic foreign bodies consisted of a strip, rod-like high density image surrounding soft tissue on CT scan and hypointense on both T1WI and T2WI with MRI images. Complete removal of the intraorbital foreign body was accomplished by anterior orbitotomy in 21 patients and lateral orbitotomy in the remaining patients. Removal was achieved in a single surgery for 21 patients whereas 2 surgeries were required for the remaining patients. No postoperative complications were reported in any of the patients. CONCLUSIONS: Intraorbital foreign bodies requiring surgical removal mostly involved organic foreign bodies. These were most commonly found in male children. Orbital imaging played a critical role for an accurate presurgical diagnosis. Anterior orbitotomy provided the best surgical outcomes. PMID- 26267573 TI - Endotine Midface for Soft Tissue Suspension in Zygoma Fracture. AB - Treatment of zygomatic fractures necessitates dissection beneath the soft tissues of the cheek. Inadequate resuspension may lead to deformities, including cheek ptosis, lower lid ectropion, and lateral canthal dystopia. The authors present their experience using a biodegradable suspension device for cheek flap resuspension. Patients who received open reduction for unilateral zygomatic fracture between January, 2006 and December, 2013 at a single center were included in the study. Patients could choose whether or not to have Endotine midface inserted. Patients rated satisfaction on facial symmetry. Computed tomography (CT) at 15 months was assessed for soft tissue thickness at the level of the midpoint of the nasolabial fold on each side. Photographs at 15 months were viewed by 3 blinded plastic surgeons and rated for cheek drooping. The results for all 3 parameters were compared between the Endotine group and the control group. A total of 83 patients were included (43 in the Endotine group and 39 in the control group). Patient satisfaction scores were statistically higher (P = 0.03) in the Endotine group (3.70 +/- 0.76) than the control group (2.85 +/- 0.96). Computed tomography soft tissue thickness score ratio between affected and unaffected side was significantly lower (P < 0.001) in the Endotine group than the ratio in the control group. Photography evaluation score difference between affected and unaffected side for the Endotine group (0.70 +/- 0.77) was significantly (P = 0.041) smaller than the control group (1.92 +/- 1.24). Endotine midface is easy to apply and effective in repositioning the elevated cheek flap in zygomatic fracture patients. PMID- 26267574 TI - Experimental Research on Intranasally Administered Dexmedetomidine. PMID- 26267575 TI - Classification and Management of Metopic Craniosynostosis. AB - BACKGROUND: In the craniofacial surgery literature, there is a wide disparity of opinions regarding the management of nonsyndromic metopic synostosis. With the lack of level I evidence to support a particular regimen, we aimed to elucidate the current state of practice among craniofacial surgeons with the hope of establishing a standard of care. METHODS: A survey was sent to 102 craniofacial surgeons. The survey featured 2 parts: clinical scenarios and questions regarding the following: primary indication for surgery, preference of timing, and choice of operative intervention for patients presenting with nonsyndromic isolated metopic synostosis. Surgeons were also queried regarding preoperative, intraoperative, and postoperative protocols. RESULTS: The total response rate was 72% (73/102) for the clinical scenarios and 63% (64/102) for the complete survey. There was a large discrepancy when classifying and managing mild metopic synostosis, with between 16% and 35% of surgeons electing to operate on a mild case. All surgeons agreed to operate on moderate and severe cases. For 95% of respondents, skull deformity was the primary indication for treatment of craniosynostosis. Open surgical management was most commonly performed at 6 months (29%) of age. Open frontal orbital advancement was the most commonly performed procedure in mild (27%), moderate (77%), and severe (89%) cases. Endoscopic approaches were more likely to be used in milder cases by 19% of surgeons. CONCLUSION: Our survey demonstrates that there is a wide disparity of opinion among craniofacial surgeons regarding the diagnosis and management of mild nonsyndromic metopic synostosis. LEVEL OF EVIDENCE: Diagnostic, level 5. PMID- 26267576 TI - Pediatric Cranial Vault Fractures: Analysis of Demographics, Injury Patterns, and Factors Predictive of Mortality. AB - BACKGROUND: Pediatric cranial vault fractures are a unique subset of injuries that pose distinct management and treatment challenges. They are anatomically distinct from their adult counterparts with potential implications on the development of the brain and craniofacial skeleton, and require unique considerations for management and treatment outcomes.A detailed analysis of the characteristics and outcomes of pediatric cranial vault fractures remains understudied in this population. Thus, the aim of this study was to characterize the demographics, injury patterns, operative interventions, concomitant injuries, and factors predictive of mortality in pediatric patients sustaining cranial vault fractures. METHODS: A retrospective review of patients less than 18 years of age presenting to the emergency department of a pediatric level I trauma center between 2000 and 2005 with skull fractures was performed. All patients were included regardless of treating specialty, treatment modality, or inpatient status. Patients were stratified into 3 groups (age < = 5 yrs, 5.1-11 yrs, and >11 yrs). ZIP codes were mapped using ArcGIS 10.2 Software (ESRI Inc, Redlands, CA) with ZIP code shapefiles from ESRI's ArcGIS Online. Socioeconomic and demographic variables at the ZIP code level were linked to each geocoded location using the United States Census Bureau summary files, and spatial clusters of injury were performed using GeoDa to conduct a test of local indicator of spatial autocorrelation. Statistical analysis was performed using the SPSS version 17 (SPSS Inc, Chicago, IL). RESULTS: A total of 923 consecutive patients met the inclusion criteria for the study. Caucasian (P < 0.001) males (P = 0.055) were most likely to sustain cranial vault fractures. The average age at injury was 5.97 years. Falls (53.7%) were the most common cause of injury across all age groups, followed by collisions (20.8%), with falls being more common in the youngest age group (< = 5 yrs), and collisions being more common in the older age groups. Direct objects to the head had the highest rate of surgical intervention (P < 0.001). Parietal bone fractures were more frequent in the youngest age group, while frontal and temporal bone fractures were more common in the older age groups. Increasing age was an independent predictor of the need for surgical intervention (P < 0.0001). The overall incidence of blindness and hearing loss was low, and increased with increasing age. Patients with fractures as a result of violent mechanisms were more likely to come from highly impoverished zip codes, compared with patients with nonviolent mechanisms of injury (19.6% versus 8%). Overall mortality was low (2.9%). Temporal bone fractures had the greatest risk of mortality (P < 0.001) with age > = 5 years being an independent predictor of mortality (P < 0.001). Victims of falls, and patients with associated gastrointestinal or musculoskeletal injuries, had a statistically significant increased chance of survival, whereas victims of collisions and patients with concomitant cervical spine, cardiothoracic, or respiratory injuries had a significantly increased risk of death. CONCLUSIONS: Pediatric cranial vault fracture injury patterns are significantly correlated with demographics, mechanisms of injury, presence and type of concomitant injuries, need for surgical intervention, and mortality. Although the need for operative intervention and overall mortality is low, these variables play significant roles in portending prognosis, and an understanding of the metrics presented herein will enable practitioners optimize management and treatment in this unique patient population. PMID- 26267577 TI - Distinguishing Goldenhar Syndrome from Craniofacial Microsomia. AB - Goldenhar syndrome is characterized by the typical features of craniofacial microsomia (CFM) with the addition of epibulbar dermoids and vertebral anomalies. The aim of this study is to examine the objective differences between patients carrying a diagnosis of Goldenhar syndrome to those diagnosed with CFM. Thus, we performed an Institutional Review Board-approved retrospective chart review on all patients who presented with a diagnosis of CFM or Goldenhar syndrome from January 1990 to December 2012. Demographic, diagnosis, OMENS+ classification, accompanying diagnoses, and radiographic data were collected. For subjective analysis, subgroups were designed based on the diagnosis Goldenhar syndrome or CFM per history. For objective analysis, subgroups were designed based on the presence of epibulbar dermoids and/or vertebral anomalies. The cohorts were compared with respect to associated medical abnormalities and severity of CFM features. One hundred thirty eight patients met inclusion criteria. Epibulbar dermoids and vertebral anomalies were seen in 17% and 34% of the patients, respectively. Only 10 patients (7.2%) had both epibulbar dermoids and vertebral anomalies. The subjective "Goldenhar" group (N = 44, 32%) was found to have a higher percentage of bilaterally affected patients (P = 0.001), a more severe mandibular deformity (P = <0.001), a more severe soft tissue deformity (P = 0.01), and a higher incidence of macrostomia (P = 0.003). In the objective subgroup analysis, the only significant difference was found in the degree of soft tissue deficiency (P = 0.049). The diagnostic criteria of Goldenhar syndrome remain unclear, thereby making clinical use of the term "Goldenhar" inconsequential. Goldenhar syndrome is over diagnosed subjectively in patients who show more severe CFM features. PMID- 26267578 TI - Comparison of Direct and Digital Measures of Cranial Vault Asymmetry for Assessment of Plagiocephaly. AB - Measurement of cranial vault asymmetry (CVA) is a common feature in the treatment of patients with deformational plagiocephaly (DP). In many cases, this measure is the primary marker of improvement. CVA is typically measured with calipers and is subject to interrater variability. There is little research comparing results of calipers with those of three-dimensional (3D) photogrammetry.Fifty nine visits were made by 51 children previously diagnosed with DP. Thirty eight were male and 13 were female. Thirty one of the visits included a 3D photograph. Direct measures were obtained by 2 experienced anthropometrists and included head length, width, circumference, and CVA. Their results were compared to digital measures including measures unobtainable with calipers, asymmetry of head circumference and global asymmetry.The interrater reliability of all caliper measures was excellent (intraclass correlation coefficients > 0.94). Caliper and digital measures of length, width, cephalic index, and circumference were strongly correlated (R > 0.90). There was a consistent bias, caliper measures being 1 to 4 mm shorter than their digital analogues. Caliper measured CVA was highly correlated (R > 0.90) with the directly corresponding digital measures. It was poorly correlated with measures of overall hemispheric asymmetry (R < 0.10).The cranial measurements of children with DP taken independently by 2 experienced anthropometrists showed excellent interrater reliability. Caliper measures are consistently smaller than the digital measures, presumably due to pressure of the calipers and/or the use of skullcaps during photography. Like circumference and other assessments, cranial vault asymmetry measures correlate well with their analogous digital measurements. PMID- 26267579 TI - Frontal Encephalocele Associated With a Bilateral Tessier Number Three Cleft and Fraser Syndrome. AB - Oblique craniofacial clefts and encephaloceles are each rare conditions, and only a few instances of these findings in combination have been described. Each pathologic entity presents a unique reconstructive challenge. The authors report the case of a male infant who presented with a large right frontoencephalocele and bilateral Tessier number 3 clefts. A review of the pertinent literature, including specific considerations related to perioperative management and technical aspects of the surgical approach, is discussed. PMID- 26267580 TI - Calvarial Regeneration With Use of Acellular Dermal Matrix in Aplasia Cutis Congenita. AB - Aplasia cutis congenital (ACC) is a rare congenital anomaly, most commonly affecting the scalp, with a variable penetrance ranging from a small (<2 cm) area of missing skin to large defects characterized by absent skin, subcutaneous tissue, calvarium, and dura. Calvarial reconstruction in ACC can be challenging. Due to exposed neurologic structures, in large defects, ACC has a high mortality rate. A stable reconstruction is optimally achieved shortly after birth to minimize complications. Herein the authors present a case of a neonate with an extensive (4.5 * 7 cm) cutis aplasia defect associated with absent skin, subcutaneous tissue, calvarium, dura, and with exposed cortical surface and sagittal sinus. This defect was successfully reconstructed in a single stage with the use of an acellular dermal matrix/skin graft construct. The acelluar dermal matrix served as a scaffold for tissue ingrowth, promoting regeneration of the bony calvarium as well as soft tissue. At 18-month follow-up, the patient exhibits a 50% smaller calvarial defect as well as stable skin coverage. PMID- 26267581 TI - Reconstruction With Modified Face Lift and Orbicularis Oculi V-Y Advancement Flap for Sebaceous Carcinoma on Temple Area. AB - Extraocular sebaceous carcinoma that occurs on sebaceous gland is a rare malignant cancer with unknown causes and nonspecific clinical characters, but with distinct pathology and immunohistochemical finding. In Kangnam Sacred Heart Hospital, there was a case that the result of preoperative punch biopsy was squamous cell carcinoma and malignant proliferating trichilemmal tumor, but that of postoperative permanent biopsy was sebaceous carcinoma. The type of tumor, differentiation, location, and aesthetic results are considered to get both recurrence-safe and aesthetically pleasing result. Various flaps were considered, and modified face-lift flap, forehead rotation flap, orbicularis oculi V-Y advancement flap were planned. There were no sign of recurrence of cancer or functional and aesthetical deformities 6 months after the surgery. PMID- 26267582 TI - Electromyographic Evaluation of Temporalis Muscle Following Temporalis Tendon Transfer (Facial Reanimation) Surgery. AB - Facial paralysis is a significant functional and aesthetic handicap. Many techniques have been defined for facial reanimation. The aim of the study was to evaluate postoperative electromyographical (EMG) activity of temporalis muscle to assess the potential neural impairments related to the surgical procedure. METHODOLOGY: Four patients with facial paralysis were operated with the temporalis muscle tendon transfer technique. Simultaneous surface electromyographic (sEMG) activity at first postoperative year from the bilateral temporalis and masseter muscles was obtained at mandibular rest position and then during maximal clenching. RESULTS: Patients were followed for a minimum period of 18 months. Surface electromyographic evaluations during passive state revealed similar values for the operated and contralateral side. Measurements during active "clench-smiling" of the jaw revealed similar amplitudes for both muscles of the operated side in all cases except case #2. Case #2 revealed lower values for both measurements of temporalis and masseter muscles of the operated side compared with the contralateral side. Dissonant results of case #2 can be the consequence of impaired temporalis muscle activity because of the tension on the muscle as a consequence of overcorrection. CONCLUSION: Temporalis muscle transfer to the perioral region does not hinder contractility of the muscle as long as the facial deformity is not overcorrected. PMID- 26267583 TI - Characteristics of Maxillary Morphology in Unilateral Cleft Lip and Palate Patients Compared to Normal Subjects and Skeletal Class III Patients. AB - This study is to investigate the anatomical features of maxillae in unilateral cleft lip and palate (UCLP) patients with maxillary retrusion. Additionally, the dissimilarities of retruded maxillae between the UCLP patients and the skeletal class III patients were compared. Craniofacial measurements were carried out among 32 UCLP adult patients with maxillary retrusion (GC), 24 adult patients in class III (SNA < 80 degrees , ANB < 0 degrees ) patients (GIII), and 32 normal controls (GN). The authors measured the width and length of the maxillae, as well as their relative positions to the coronal plane passing through basion. The independent sample group t test was performed, and P < 0.05 was regarded as statistically significant. In the GC group, the anterior and posterior maxillary length (A1-P3M?CP and P3M-P6M?CP) and overall maxillary length (A1-P6M?CP) at the dental level, the interdental widths of the maxillae, the maxillary volume (GM), and the volume consisting of maxilla and maxillary sinus (GT) significantly reduced compared with the GN group (P < 0.05). The distances from the points on the maxillae to the coronal plane (A1?CP, P3M?CP, and P6M?CP) in the GC and GIII groups were smaller than those in the GN group (P < 0.05). In summary, for the UCLP patients, the decreased prominence of maxillary complex could be mainly caused by the shortened maxillary length; meanwhile, posterior position of the maxillary body may have some influence on the maxillary protrusion. While for the class III patients, maxillary retrusion was resulted from malposition and malmorphology on an equal basis. PMID- 26267584 TI - Double-Opposing Unilobar Rotation Flaps in the Reconstruction of Moderate-to Large Defects of the Scalp. AB - Closure of medium-to-large-size defects of the scalp are often associated with unacceptable aesthetic results, wound break down, alopecia, and excessive scarring. The authors present 2 cases of double-opposing unilobar rotation flaps for the reconstruction of large, that is, at least 7 cm diameter, full thickness defects of the scalp. Unlike previously described double flap closures of scalp defects, the double-opposing unilobar rotation flap design are true rotation flaps, which require a Burow triangle excisions and which have a versatility in both width and length of design to accommodate closure of large defects of the scalp. Some of the advantages of this technique are the retention of hair-bearing skin without distortion of the follicle position, an aesthetically pleasing scar, minimal tension at the wound closure site, and the versatility as well as simplicity of the technique. PMID- 26267585 TI - Effect of Restraining Devices on Facial Fractures in Motor Vehicle Collisions. AB - The aim of this systematic review is to summarize and critically evaluate the evidence for or against the effectiveness of restraining devices on facial fractures in motor vehicle collisions (MVCs).In a PubMed search, the search terms "facial bone fracture and seat belt," "facial bone fracture and air bag," and "facial bone fracture and restraining" were used. The authors abstracted the odds ratio (OR) and 95% confidence intervals (CIs) from each study. Weighted mean differences and 95% CIs were also calculated. The statistical analysis was performed with Review Manager (The Nordic Cochrane Centre).The authors found 30 potentially relevant articles, of which 6 articles met our inclusion criteria. Five studies were subgrouped, and a meta-analysis of these data suggested beneficial effects of seat belts on decreasing facial fractures in MVCs (n = 15,768,960, OR, 0.46, 95% CI = 0.35-0.60). Three studies were subgrouped, and a meta-analysis of these data suggested that there were beneficial effects of seat belts and air bags on decreasing facial fractures in MVCs (n = 15,768,021, OR, 0.59, 95% CI = 0.47-0.74). Four studies were subgrouped, and a meta-analysis of these data suggested there were no significant effects of an air bag on decreasing facial fracture in MVCs (n = 15,932,259, OR, 1.00, 95% CI = 0.72 1.39).A seat belt alone (OR, 0.46) or a seat belt and an air bag (OR, 0.59) were effective to decrease facial fractures in MVCs. However, air bags alone had no significant effect (OR, 1.00). In using air bags, seat belt should be applied together to prevent facial fractures in motor vehicle injuries. PMID- 26267586 TI - Recurrent Lymphoepithelial Carcinoma of the Parotid Gland. AB - BACKGROUND: Lymphoepithelial carcinomas (LECs) are rare tumors of parotid gland. Although few cases were reported in literature, there is no reported recurrent case. METHOD: The authors report a case of recurrent LEC after 8 months of primary surgery. Total parotidectomy and selective neck dissection surgery were performed. Radiation therapy after surgery was planned. Patient had partial facial weakness in the early postoperative period that was getting better with follow-up. CONCLUSIONS: In the diagnosis of LECs of parotid region, nasopharyngeal carcinomas must be excluded. If LECs are not treated properly, recurrences may occur. PMID- 26267587 TI - Clinicopathologic, Cone-Beam Computed Tomographic, and Surgical Findings in a Unique Maxillary Hybrid Odontogenic Tumor. PMID- 26267588 TI - Mandibular Osteomyelitis Caused by Periodontal Treatment in HIV Patient. PMID- 26267589 TI - Dielectric discontinuity in equilibrium block copolymer micelles. AB - The surface tension between the hydrophobic core and the solvent is known to play a major role in the self-assembly of diblock copolymer micelles in solution. Coulombic forces are also very important in the case of aggregates with weakly charged coronas. The aggregation number and morphology are often tuned by the addition of electrolytes to the solution via electrostatic screening and an eventual change in solvent quality. However, when the surface tension is low enough, dielectric discontinuity between the core and the solvent becomes important enough in comparison to other mechanisms, driving the surface tension at the same time it screens electrostatic interactions in the corona. Below, we demonstrate the importance of this effect for micelles with neutral and weakly charged coronas. PMID- 26267590 TI - Pharmacokinetics, safety, and cardiovascular tolerability of phenylephrine HCl 10, 20, and 30 mg after a single oral administration in healthy volunteers. AB - BACKGROUND AND OBJECTIVES: Phenylephrine HCl 10 mg has been used as a nasal decongestant for over 50 years, yet only limited pharmacokinetic and metabolic data are available. The purpose of this study was to evaluate single-dose pharmacokinetics and safety of phenylephrine HCl 10, 20, and 30 mg and to assess cardiovascular tolerability compared with baseline and placebo in healthy volunteers. METHODS: Twenty-eight adults were enrolled in this randomized, double blind, placebo-controlled, single-dose, four-treatment crossover study. Subjects remained housed for 6 days to permit time-matched, serial measurements of pulse, blood pressure, and electrocardiograms (ECGs) for baseline and complete treatments on consecutive days. After fasting overnight, subjects were dosed with oral phenylephrine HCl 10, 20, or 30 mg or placebo. Pharmacokinetic blood samples were collected over 7 h, whereas pulse, blood pressure, and ECGs were measured over 12 h. Urine was collected over each 24-h period to quantify phenylephrine and metabolites. RESULTS: After oral administration, phenylephrine was rapidly absorbed with median times to maximum plasma concentrations (t max) from 0.33 to 0.5 h. For phenylephrine HCl 10, 20, and 30 mg, the mean (standard deviation) maximum concentration (C max) was 1354 (954), 2959 (2122), and 4492 (1978) pg/mL, and total systemic exposure [area under the plasma concentration-time curve from time zero to infinity (AUCinfinity)] was 955.8 (278.5), 2346 (983.8), and 3900 (1764) pg.h/mL, respectively. Both parameters increased disproportionally with increasing dose, as beta >1 in the power model. Negligible amounts of phenylephrine and phenylephrine glucuronide were excreted in urine. With increasing dose, percentages by dose of phenylephrine sulfate decreased, whereas percentages of 3-hydroxymandelic acid increased. Eight subjects reported nine mild adverse events; one (somnolence) was deemed to be treatment related. Means of time-matched differences in pulse and blood pressure from baseline showed similar fluctuations over 12 h among phenylephrine HCl doses and placebo, although small differences in systolic pressure were observed during the initial 2 h. No apparent dose-related effects were observed for Fridericia-corrected QT interval (QTcF) values, and individual changes from time-matched baseline (DQTcF). CONCLUSIONS: Maximum and total systemic exposures following singe doses of phenylephrine HCl 10, 20, and 30 mg increased disproportionally with increasing dose. Safety and cardiovascular tolerability were comparable among doses and placebo. PMID- 26267591 TI - Caring from Afar: Asian H1B Migrant Workers and Aging Parents. AB - With the growth in engineering/technology industries, the United States has seen an increase in the arrival of highly skilled temporary migrant workers on H1B visas from various Asian countries. Limited research exists on how these groups maintain family ties from afar including caring for aging parents. This study explores the experiences and challenges that Asian H1B workers face when providing care from a distance. A total of 21 Chinese/Taiwanese, Korean, and Indian H1B workers participated in in-depth qualitative interviews. Key findings indicate that despite distance, caring relationships still continue through regular communications, financial remittances, and return visits, at the same time creating emotional, psychological, and financial challenges for the workers. Findings highlight the need for further research in understanding how the decline of aging parent's health impacts the migrants' adjustment and health in the United States. PMID- 26267592 TI - Comparison of patients' confidence in office, ambulatory, and home blood pressure measurements as methods of assessing for hypertension. AB - OBJECTIVE: Uncertainty exists when relying on office (clinic) blood pressure (BP) measurements to diagnose hypertension. Home BP monitoring and ambulatory BP monitoring (ABPM) provide measurements that are more strongly associated with cardiovascular disease. The degree to which patients exhibit uncertainty about office BP measurements is unknown, as is whether they would have less uncertainty about other BP measurement methods. We therefore assessed people's confidence in methods of BP measurement, comparing perceptions about office BP monitoring, home BP monitoring, and ABPM techniques. METHODS: We surveyed adults who were 30 years or older (n=193), all whom had undergone office BP measurements, two sessions of 24-h ABPM, and two 5-day periods of home BP monitoring. Respondents were asked to indicate their level of confidence on a 1 to 9 scale that BP measurements represented their 'usual' BP. RESULTS: Respondents had least confidence that assessments of BP made by office measurements (median 6) represented usual BP and greater confidence that assessments made by home BP monitoring (median 7, P<0.0001 vs. office) and ABPM (median 8, P<0.0001 vs. office) did so. Confidence levels did not vary significantly by BP levels, age, sex, race, or education level. CONCLUSION: The finding that patients do not have a great deal of confidence in office BP measurements, but have a higher degree of confidence in home BP and ambulatory BP assessment methods may be helpful in guiding strategies to diagnose hypertension and improve antihypertensive medication adherence. PMID- 26267593 TI - Heart rate variability assessment with fingertip photoplethysmography and polar RS800cx as compared with electrocardiography in obese adolescents. AB - AIM: This study investigated the accuracy and reliability of short-term resting heart rate variability (HRV) assessment by fingertip photoplethysmography (PPG) and using a cardiofrequencimeter (Polar RS800cx) in obese adolescents. Obesity in adolescents may be related to autonomic dysfunction due to insulin resistance and/or increased central fat. This fact may affect the accuracy and reliability of the evaluation of autonomic activity at rest. METHODS: Fourteen adolescents (15+/-2 years) classified as obese and exhibiting insulin resistance underwent the following procedures: (a) anthropometric measurements, and (b) two 25-min HRV recordings in a supine position conducted simultaneously using ECG, PPG, and Polar RS800cx. RESULTS: The results showed significant correlations between HRV markers obtained using Polar RS800cx and PPG and those obtained from ECG, with coefficients of determination (R) and intraclass correlation coefficients ranging from 0.60 to 0.98 (P-value ranging from 0.03 to 0.05) and 0.70 to 0.99 (P-value ranging from 0.01 to 0.05), respectively. The technical error of measurement and intraclass correlation coefficients for test-retest reliability ranged from 8.9 to 45.8% and 0.38 to 0.68 for ECG, 8.0 to 30.5% and 0.29 to 0.61 for Polar RS800cx, and 7.2 to 54.6% and 0.45 to 0.64 for PPG, respectively. CONCLUSION: HRV indices calculated by Polar RS800cx and PPG appear to be as accurate and reproducible as data from ECG when evaluating the autonomic control of heart rate at rest in obese adolescents. PMID- 26267594 TI - Adverse Childhood Events are Related to the Prevalence of Asthma and Chronic Obstructive Pulmonary Disorder Among Adult Women in Hawaii. AB - PURPOSE: In the US, women surpass men in the prevalence of lung diseases. Limited studies exist on the association of adverse childhood events (ACEs) to asthma and chronic obstructive pulmonary disorder (COPD) particularly among women and cohorts of understudied populations (e.g., Pacific Islanders). This study evaluated the ACEs-asthma and ACEs-COPD relationships among women in Hawaii and the contribution of poor health factors (smoking, binge drinking, and obesity) in these associations. METHODS: Using data from 3363 women in the Behavioral Risk Factor Surveillance System-Hawaii, we assessed how self-reported ACEs [count and type (household dysfunction, and physical, verbal and sexual abuse)] relate to asthma and COPD. Multivariable log-binomial regression, accounting for the sampling design, and model adjustments for socio-demographics, healthcare access, emotional support, current smoking, binge drinking, and BMI status were used to generate prevalence ratios. RESULTS: For every increase in ACE count, the likelihood for asthma increased by 7 % (CI = 1.02-1.13), and for COPD, by 21 % (CI = 1.12-1.31) accounting for socio-demographics, healthcare access, and emotional support. Verbal abuse was also associated with greater likelihood for asthma independent of these covariates (PR = 1.43, CI = 1.14-1.79). Household dysfunction (PR = 1.82, CI = 1.15-2.82) and physical (PR = 2.01, CI = 1.20-3.37), verbal (PR = 2.24, CI = 1.38-3.65) and sexual (PR = 1.81, CI = 1.10-2.97) abuse were all associated with COPD using similar adjustments. Additional adjustment for smoking, binge drinking, and BMI status did not impact the ACE-asthma associations and only modestly attenuated the ACE-COPD relationships. CONCLUSIONS: Primary and secondary prevention of ACEs may optimize the health of young girls in Hawaii, and reduce the burden of asthma and COPD among women in the state. PMID- 26267595 TI - Long-Term Survival After Lung Transplantation in Patients with Silicosis and Other Occupational Lung Disease. AB - BACKGROUND: Survival after lung transplantation (LTx) for patients with occupational lung disease (OLD) is not well studied. METHODS: The United Network for Organ Sharing (UNOS) database was queried from 2005 to 2013 to assess survival after LTx in patients with silicosis and non-silicotic OLD compared to non-OLD patients. RESULTS: Of 7273 adult LTx recipients, 7227 (24 with silicosis and 29 with non-silicotic OLD) were included in our univariate and Kaplan-Meier function analysis and 6370 for multivariate Cox models. Univariate Cox models did not identify survival differences in silicosis (HR 0.717; 95 % CI 0.358-1.435; p = 0.347) and non-silicotic OLDs (HR 0.934; 95 % CI 0.486-1.798; p = 0.839). Kaplan-Meier function analysis did not identify a survival disadvantage for either silicosis or non-silicotic OLD (log-rank test: chi (2) 0.93, p = 0.627). Patients with non-silicotic OLD were at risk for worse survival for the first 2.5 years post-transplant; however, at the conclusion of the study, this group had the highest survival rate. Multivariate Cox models confirmed no increased risk for mortality for silicosis (HR 1.264; 95 % CI 0.631-2.534; p = 0.509) and non silicotic OLD (HR 1.114; 95 % CI 0.578-2.147; p = 0.747). CONCLUSION: Long-term survival for adult patients with silicosis and non-silicotic OLD after LTx is not significantly different compared to the general lung transplant population. PMID- 26267596 TI - Dry Lung as a Physical Model in Studies of Aerosol Deposition. AB - A new physical model was developed to evaluate the deposition of micro- and nanoaerosol particles (NAPs) into the lungs as a function of size and charges. The model was manufactured of a dry, inflated swine lung produced by Nasco company (Fort Atkinson, WI). The dry lung was cut into two lobes and a conductive tube was glued into the bronchial tube. The upper 1-2-mm-thick layer of the lung lobe was removed with a razor blade to expose the alveoli. The lobe was further enclosed into a plastic bag and placed within a metalized plastic box. The probability of aerosol deposition was calculated by comparing the size distribution of NAPs passed through the lung with that of control, where aerosol passed through a box bypassing the lung. Using this new lung model, it was demonstrated that charged NAPs are deposited inside the lung substantially more efficiently than neutral ones. It was also demonstrated that deposition of neutral NAPs well fits prediction of the Multiple-Path Particle Dosimetry (MPPD) model developed by the Applied Research Associates, Inc. (ARA). PMID- 26267597 TI - Sustained release of bioactive protein from a lyophilized tissue-engineered construct promotes the osteogenic potential of mesenchymal stem cells. AB - Tissue-engineered constructs (TECs) seeded with mesenchymal stem cells (MSCs) represent a therapy for large bone defects. However, massive cell death in TECs in the early postimplantation period prompted us to investigate the osteoinductive mechanism of TECs. Previous studies demonstrated that stem cell extracts retained equivalent levels of bioactive proteins and exhibited an osteoinductive nature similar to that of intact cells. These data led us to hypothesize that despite the massive cell death in TECs, devitalized MSC-derived proteins remain on the scaffolds and are released to improve cell function. Here, TECs were prepared using demineralized bone matrix seeded with human umbilical cord Wharton's jelly-derived MSCs (hWJMSCs), and the cells seeded in TECs were devitalized by lyophilizing the TECs. Scanning electron microscopy, BCA protein assays, quantitative cytokine array analysis and immunofluorescent staining indicated that approximately 3 mg/cm(3) of total protein and 49 types of cytokines derived from hWJMSCs were preserved in the lyophilized TECs (LTECs). The sustainable release of total protein and cytokines from LTECs lasted for more than 2 weeks. The released protein improved the osteogenic behavior of and gene expression in MSCs. Furthermore, the lyophilized hWJMSC-derived proteins had immunoregulatory properties similar to those of live MSCs in mixed lymphocyte reactions. Collectively, we present a novel perspective on the osteoinductive mechanism of TECs and introduce LTECs as new systems for delivering multiple cytokines to enhance MSC behavior. PMID- 26267598 TI - Transcriptomic and metabolomic analyses identify a role for chlorophyll catabolism and phytoalexin during Medicago nonhost resistance against Asian soybean rust. AB - Asian soybean rust (ASR) caused by Phakopsora pachyrhizi is a devastating foliar disease affecting soybean production worldwide. Understanding nonhost resistance against ASR may provide an avenue to engineer soybean to confer durable resistance against ASR. We characterized a Medicago truncatula-ASR pathosystem to study molecular mechanisms of nonhost resistance. Although urediniospores formed appressoria and penetrated into epidermal cells of M. truncatula, P. pachyrhizi failed to sporulate. Transcriptomic analysis revealed the induction of phenylpropanoid, flavonoid and isoflavonoid metabolic pathway genes involved in the production of phytoalexin medicarpin in M. truncatula upon infection with P. pachyrhizi. Furthermore, genes involved in chlorophyll catabolism were induced during nonhost resistance. We further characterized one of the chlorophyll catabolism genes, Stay-green (SGR), and demonstrated that the M. truncatula sgr mutant and alfalfa SGR-RNAi lines showed hypersensitive-response-like enhanced cell death upon inoculation with P. pachyrhizi. Consistent with transcriptomic analysis, metabolomic analysis also revealed the accumulation of medicarpin and its intermediate metabolites. In vitro assay showed that medicarpin inhibited urediniospore germination and differentiation. In addition, several triterpenoid saponin glycosides accumulated in M. truncatula upon inoculation with P. pachyrhizi. In summary, using multi-omic approaches, we identified a correlation between phytoalexin production and M. truncatula defense responses against ASR. PMID- 26267599 TI - The efficacy of the interferon-gamma release assay for diagnosing cervical tuberculous lymphadenitis: A prospective controlled study. AB - OBJECTIVES/HYPOTHESIS: The whole-blood interferon (IFN)-gamma release assay (IGRA) has been studied mainly for diagnosing latent tuberculosis (TB). We prospectively evaluated its diagnostic usefulness in patients with suspected cervical TB lymphadenitis. STUDY DESIGN: Prospective cohort study. METHODS: An IGRA was performed in subjects with suspected TB lymphadenitis. To evaluate the diagnostic performance of the IGRA, we calculated the sensitivity and specificity of culture, radiologic imaging, polymerase chain reaction testing, fine needle aspiration, and excisional biopsy. RESULT: Of the 271 adult patients with suspected TB lymphadenitis, 42 were diagnosed with the disease. The overall sensitivity and specificity of the IGRA were 78.8% and 95.5%, respectively. When the cutoff value of IFN-gamma was set to 0.26 IU/mL, it met the inclusion criteria for suspicious TB lymphadenitis, with sensitivity and specificity of 83.3% and 95.1%, respectively. CONCLUSIONS: The IGRA is useful in diagnosing TB lymphadenitis, with high sensitivity and specificity. LEVEL OF EVIDENCE: 4. PMID- 26267600 TI - A prospective randomized controlled trial assessing the efficacy of adjunctive hyperbaric oxygen therapy in the treatment of hidradenitis suppurativa. AB - Hyperbaric oxygen therapy (HBOT) appears to enhance wound healing, increase bactericidal activity, and act synergistically with a number of antibiotics. The aim of this study was to evaluate the efficacy of HBOT as an adjunctive therapy in patients with hidradenitis suppurativa (HS) treated with a combination of systemic rifampicin and clindamycin. The study was a prospective, single-center, single-dose, open-label, randomized controlled clinical study of HBOT in patients with moderate to severe HS. Efficacy was measured by modified Sartorius score (SS), HS Severity Index (HSSI), Dermatology Life Quality Index (DLQI), and a visual analog scale (VAS) before treatment and after the completion of 4 and 10 weeks of treatment. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were also measured. Forty-three patients were enrolled in the study. More patients in the HBOT than in the control group showed a decrease of >=50% from baseline parameters at week 10 for SS (100%), HSSI (100%), DLQI (95.5%), VAS (100%), ESR (100%), and CRP (72.7%). Clinically and statistically significant improvements from baseline were observed at 4 and 10 weeks in HSSI (P = 0.009 at both), SS (P = 0.021 at both), and DLQI (P = 0.044 at week 4, P = 0.009 at week 10). Adjunctive HBOT was considered to be effective in significantly improving antibiotic treatment of HS. The treatment was well tolerated, and no unexpected safety issues were identified. PMID- 26267601 TI - Chlorin e6-Encapsulated Polyphosphoester Based Nanocarriers with Viscous Flow Core for Effective Treatment of Pancreatic Cancer. AB - Lack of effective treatment results in the low survival for patients with pancreatic cancer, and photodynamic therapy (PDT) with photosensitizers has emerged as an effective therapeutic option for treatment of various tumors by light-generated cytotoxic reactive oxygen species (ROS) to induce cell apoptosis or necrosis. However, the poor solubility, rapid blood clearance, and weak internalization of the photosensitizer seriously inhibit its anticancer efficacy. To overcome these obstacles, a polyphosphoester-based nanocarrier (NP-PPE) is employed as the carrier of the hydrophobic photosensitizer, chlorin e6 (Ce6), for photodynamic therapy. The Ce6-encapsulated nanocarrier (NP-PPE/Ce6) significantly promoted the cellular internalization of Ce6, enhanced the generation of ROS in the tumor cells after irradiation. Therefore, the cellular phototoxicity of NP PPE/Ce6 against BxPC-3 pancreatic cancer cells was markedly enhanced than that of free Ce6 in vitro. Furthermore, NP-PPE/Ce6 improved accumulation of Ce6 in tumor tissue and treatment with NP-PPE/Ce6 significantly enhanced antitumor efficacy in human BxPC-3 pancreatic cancer xenografts. These results suggest that using a polyphosphoester-based nanocarrier as the delivery system for a photosensitizer has great potential for PDT of pancreatic cancer. PMID- 26267602 TI - Methane oxidation in a biofilter (Part 1): Development of a mathematical model for designing and optimization. AB - The aim of this work is the evaluation of the efficiency of such a biofilter, through the application of a mathematical model which describes the biological oxidation process. This mathematical model is able to predict the efficiency of the system under varying operating conditions. Literature data have been used in order to build the model. The factors that mostly affect the process and which actually regulate the entire process have been highlighted in this work. Specifically, it was found that temperature, flow and methane concentration are the most important parameters that influence the system. The results obtained from the mathematical model showed also that the biofilter system is simple to implement and manage and allows the achievement of high efficiency of methane oxidation. In the optimal conditions for temperature (between 20-30 degrees C), residence time (between 0.7-0.8 h) and methane molar fraction (between 20-25%) the efficiency of methane oxidation could be around 50%. PMID- 26267603 TI - The research conundrum of acute appendicitis. PMID- 26267604 TI - Patterns of early resuscitation associated with mortality after penetrating injuries. AB - BACKGROUND: Penetrating injuries are rare in European populations so their management represents a particular challenge. The aim was to assess early therapeutic aspects that are associated with favourable outcomes in patients with penetrating trauma. METHODS: Patients with penetrating injuries documented from 2009 to 2013 in the TraumaRegister DGU(r) were analysed. Patients with a primary admission and an Injury Severity Score (ISS) of at least 9 were included. The Revised Injury Severity Classification (RISC) II score was used for mortality prediction, and a standardized mortality ratio (SMR) calculated per hospital. Hospitals with favourable outcome (SMR below 1) were compared with those with poor outcome (SMR 1 or more). RESULTS: A total of 50 centres had favourable outcome (1242 patients; observed mortality rate 15.7 per cent) and 34 centres had poor outcome (918 patients; observed mortality rate 24.4 per cent). Predicted mortality rates according to RISC-II were 20.4 and 20.5 per cent respectively. Mean(s.d.) ISS values were 22(14) versus 21(14) (P = 0.121). Patients in the favourable outcome group had a significantly shorter time before admission to hospital and a lower intubation rate. They received smaller quantities of intravenous fluids on admission to the emergency room, but larger amounts of fresh frozen plasma, and were more likely to receive haemostatic agents. A higher proportion of patients in the favourable outcome group were treated in a level I trauma centre. Independent risk factors for hospital death following penetrating trauma identified by multivariable analysis included gunshot injury mechanism and treatment in non-level I centres. CONCLUSION: Among penetrating traumas, gunshot injuries pose an independent risk of death. Treatment of penetrating trauma in a level I trauma centre was significantly and independently associated with lower hospital mortality. PMID- 26267605 TI - Experimental study of the characteristics of a novel mesh suture (Br J Surg 2015; 102: 1285-1292). PMID- 26267607 TI - Randomized clinical trial of mast cell inhibition in patients with a medium-sized abdominal aortic aneurysm. PMID- 26267610 TI - Combined Mossbauer Spectral and Density Functional Study of an Eight-Coordinate Iron(II) Complex. AB - The iron-57 Mossbauer spectra of the eight-coordinate complex, [Fe(L(N4))2](BF4)2, where L(N4) is the tetradentate N(1)(E),N(2)(E)-bis[(1-methyl 1H-imidazol-2-yl)methylene]-1,2-benzenediimine ligand, have been measured between 4.2 and 295 K and fit with a quadrupole doublet. The fit at 4.2 K yields an isomer shift, delta(Fe), of 1.260(1) mm/s and a quadrupole splitting, DeltaE(Q), of 3.854(2) mm/s, values that are typical of a high-spin iron(II) complex. The temperature dependence of the isomer shift yields a Mossbauer temperature, Theta(M), of 319(27) K and the temperature dependence of the logarithm of the Mossbauer spectral absorption area yields a Debye temperature, Theta(D), of 131(6) K, values that are indicative of high-spin iron(II). Nonrelativistic single point density functional calculations with the B3LYP functional, the full 6-311++G(d,p) basis set, and the known X-ray structures for [Mn(L(N4))2](2+), [Mn(L(N4))2](ClO4)2, 1, [Fe(L(N4))2](2+), and [Fe(L(N4))2](BF4)2, 2, yield small electric field gradients for the manganese(II) complexes and electric field gradients and s-electron densities at the iron-57 nuclide that are in good to excellent agreement with the Mossbauer spectral parameters. The structure of 2 with a distorted square-antiprism C1 iron(II) coordination symmetry exhibits four different Fe-N(imid) bonds to the imidazole nitrogens with an average bond distance of 2.253(2) A and four different Fe-N(imine) bonds to the benzenediimine nitrogens, with an average bond distance of 2.432(2) A; this large difference yields the large observed DeltaE(Q). An optimization of the [Fe(L(N4))2](2+) structure leads to a highly symmetric eight-coordination environment with S4 symmetry and four equivalent Fe-N(imid) bond distances of 2.301(2) A and four equivalent Fe-N(imine) bond distances of 2.487(2) A. In contrast, an optimization of the [Mn(LN4)2](2+) structure leads to an eight-coordination manganese(II) environment with D(2d) symmetry and four equivalent Mn-N(imid) bond distances of 2.350(3) A and four equivalent Mn-N(imine) bond distances of 2.565(3) A. PMID- 26267609 TI - Macrophage-tumor cell fusions from peripheral blood of melanoma patients. AB - BACKGROUND: While the morbidity and mortality from cancer are largely attributable to its metastatic dissemination, the integral features of the cascade are not well understood. The widely accepted hypothesis is that the primary tumor microenvironment induces the epithelial-to-mesenchymal transition in cancer cells, facilitating their escape into the bloodstream, possibly accompanied by cancer stem cells. An alternative theory for metastasis involves fusion of macrophages with tumor cells (MTFs). Here we culture and characterize apparent MTFs from blood of melanoma patients. METHODS: We isolated enriched CTC populations from peripheral blood samples from melanoma patients, and cultured them. We interrogated these cultured cells for characteristic BRAF mutations, and used confocal microscopy for immunophenotyping, motility, DNA content and chromatin texture analyses, and then conducted xenograft studies using nude mice. FINDINGS: Morphologically, the cultured MTFs were generally large with many pseudopod extensions and lamellipodia. Ultrastructurally, the cultured MTFs appeared to be macrophages. They were rich in mitochondria and lysosomes, as well as apparent melanosomes. The cultured MTF populations were all heterogeneous with regard to DNA content, containing aneuploid and/or high-ploidy cells, and they typically showed large sheets (and/or clumps) of cytoplasmic chromatin. This cytoplasmic DNA was found within heterogeneously-sized autophagic vacuoles, which prominently contained chromatin and micronuclei. Cultured MTFs uniformly expressed pan-macrophage markers (CD14, CD68) and macrophage markers indicative of M2 polarization (CD163, CD204, CD206). They also expressed melanocyte-specific markers (ALCAM, MLANA), epithelial biomarkers (KRT, EpCAM), as well as the pro carcinogenic cytokine MIF along with functionally related stem cell markers (CXCR4, CD44). MTF cultures from individual patients (5 of 8) contained melanoma specific BRAF activating mutations. Chromatin texture analysis of deconvoluted images showed condensed DNA (DAPI-intense) regions similar to focal regions described in stem cell fusions. MTFs were readily apparent in vivo in all human melanomas examined, often exhibiting even higher DNA content than the cultured MTFs. When cultured MTFs were transplanted subcutaneously in nude mice, they disseminated and produced metastatic lesions at distant sites. CONCLUSIONS AND HYPOTHESIS: Apparent MTFs are present in peripheral blood of patients with cutaneous melanomas, and they possess the ability to form metastatic lesions when transplanted into mice. We hypothesize that these MTFs arise at the periphery of primary tumors in vivo, that they readily enter the bloodstream and invade distant tissues, secreting cytokines (such as MIF) to prepare "niches" for colonization by metastasis initiating cells. PMID- 26267611 TI - Management of pediatric renal tumor: Past and future trials of the Japan Wilms Tumor Study Group. AB - The Japan Wilms Tumor Study group (JWiTS) was founded in 1996 to improve outcomes for children with renal tumor in Japan, and a nationwide multicenter cooperative study was initiated thereafter. JWiTS-1 (1996-2005) was analyzed, and JWiTS-2 (2005-2014) is now under analysis; the following problems have been identified and used to decide future study protocol: (i) there has been a decline in survival rate for patients with rhabdoid tumor of the kidney (RTK) and new treatment strategies are required; (ii) the survival rate for bilateral Wilms tumors (BWT) has improved, but results for renal preservation are unsatisfactory; (iii) the prognosis of stage IV favorable nephroblastoma is very good, suggesting that the current protocols provide overtreatment, particularly for patients with lung metastasis; and (iv) no effective biological risk factors exist for predicting the outcome of Wilms tumor, and a study of the genetic changes of these tumors is necessary to determine biological markers for use in risk classification. To solve these issues, the development of a new risk classification of pediatric renal tumors is required. In addition, different study protocols should be developed according to the risk-based classification of the patients. Further, a new study protocol for BWT began in 2015, and new study protocols are being prepared for RTK, and for Wilms tumor with lung metastasis. In addition, an analysis of biological markers with regard to risk classification is to be performed. Furthermore, to create new protocols for patients with rare renal tumors, international collaboration with Children's Oncology Group and International Society of Pediatric Oncology is necessary. PMID- 26267612 TI - A Consortium Approach to Surgical Education in a Developing Country: Educational Needs Assessment. AB - IMPORTANCE: Surgical disease is a global health priority, and improving surgical care requires local capacity building. Single-institution partnerships and surgical missions are logistically limited. The Alliance for Global Clinical Training (hereafter the Alliance) is a consortium of US surgical departments that aims to provide continuous educational support at the Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania (MUHAS). To our knowledge, the Alliance is the first multi-institutional international surgical collaboration to be described in the literature. OBJECTIVE: To assess if the Alliance is effectively responding to the educational needs of MUHAS and Muhimbili National Hospital surgeons. DESIGN, SETTING, AND PARTICIPANTS: During an initial 13-month program (July 1, 2013, to August 31, 2014), faculty and resident teams from 3 US academic surgical programs rotated at MUHAS as physicians and teachers for 1 month each. To assess the value of the project, we administered anonymous surveys. MAIN OUTCOMES AND MEASURES: Anonymous surveys were analyzed on a 5-point Likert-type scale. Free-text answers were analyzed for common themes. RESULTS: During the study period, Alliance members were present at MUHAS for 8 months (1 month each). At the conclusion of the first year of collaboration, 15 MUHAS faculty and 22 MUHAS residents completed the survey. The following 6 areas of educational needs were identified: formal didactics, increased clinical mentorship, longer-term Alliance presence, equitable distribution of teaching time, improved coordination and language skills, and reciprocal exchange rotations at US hospitals. The MUHAS faculty and residents agreed that Alliance members contributed to improved patient care and resident education. CONCLUSIONS AND RELEVANCE: A multi-institutional international surgical partnership is possible and leads to perceived improvements in patient care and resident learning. Alliance surgeons must continue to focus on training Tanzanian surgeons. Improving the volunteer surgeons' Swahili-language skills would be an asset. Future efforts should provide more teaching coverage, equitably distribute educational support among all MUHAS surgeons, and collaboratively develop a formal surgical curriculum. PMID- 26267613 TI - Facile Synthesis of 3-N-Alkyl Pyrimidin-2,4-diones from N-Sulfonyloxy Maleimides and Amines. AB - Reaction of variously substituted N-trifluoromethanesulfonyloxy maleimides with primary amines in the presence of potassium carbonate in DMF at room temperature results in the formation of 3-N-alkyl pyrimidin-2,4-diones in good yield. PMID- 26267614 TI - Cytogenetic and Molecular Data Suggest Deuterodon pedri Eigenmann, 1907 (Teleostei: Characidae) Is a Member of an Ancient Coastal Group. AB - The genus Deuterodon has been taxonomically recently redefined. Seven of its species have been included in this genus, whereas three others are regarded as Incertae Sedis in Characidae. One of latter is Deuterodon pedri, an endemic species from Santo Antonio River in Minas Gerais. Cytogenetic and molecular data on 21 specimens of D. pedri allowed to reevaluate the phylogenetic position of this taxon. The specimens showed karyotypic formula 12m+12sm+20st+6a, low heterochromatin content, nucleolar organizer regions present in two chromosome pairs, and 10 and 2 labeled regions by fluorescence in situ hybridization with 18S and 5S probes respectively, a karyotype similar to Deuterodon stigmaturus. The phylogenetic tree generated by a cytochrome oxidase subunit I fragment revealed that D. pedri and Deuterodon singularis are closely related and are the sister-group of Deuterodon parahybae, Deuterodon iguape, Astyanax giton, Astyanax intermedius, Astyanax ribeirae, Astyanax scabripinnis, and Probolodus heterostomus. The same arrangement was partially recovered with the nuclear gene RAG2. Our data indicate the genus Deuterodon is not monophyletic and that it is closely related to other species that occur in Brazil coastal basins. PMID- 26267615 TI - Combining the Estimated Date of HIV Infection with a Phylogenetic Cluster Study to Better Understand HIV Spread: Application in a Paris Neighbourhood. AB - OBJECTIVES: To relate socio-demographic and virological information to phylogenetic clustering in HIV infected patients in a limited geographical area and to evaluate the role of recently infected individuals in the spread of HIV. METHODS: HIV-1 pol sequences from newly diagnosed and treatment-naive patients receiving follow-up between 2008 and 2011 by physicians belonging to a health network in Paris were used to build a phylogenetic tree using neighbour-joining analysis. Time since infection was estimated by immunoassay to define recently infected patients (very early infected presenters, VEP). Data on socio demographic, clinical and biological features in clustered and non-clustered patients were compared. Chains of infection structure was also analysed. RESULTS: 547 patients were included, 49 chains of infection containing 108 (20%) patients were identified by phylogenetic analysis. analysis. Eighty individuals formed pairs and 28 individuals were belonging to larger clusters. The median time between two successive HIV diagnoses in the same chain of infection was 248 days [CI = 176-320]. 34.7% of individuals were considered as VEP, and 27% of them were included in chains of infection. Multivariable analysis showed that belonging to a cluster was more frequent in VEP and those under 30 years old (OR: 3.65, 95 CI 1.49-8.95, p = 0.005 and OR: 2.42, 95% CI 1.05-5.85, p = 0.04 respectively). The prevalence of drug resistance was not associated with belonging to a pair or a cluster. Within chains, VEP were not grouped together more than chance predicted (p = 0.97). CONCLUSIONS: Most newly diagnosed patients did not belong to a chain of infection, confirming the importance of undiagnosed or untreated HIV infected individuals in transmission. Furthermore, clusters involving both recently infected individuals and longstanding infected individuals support a substantial role in transmission of the latter before diagnosis. PMID- 26267617 TI - Parameter-free continuous drift-diffusion models of amorphous organic semiconductors. AB - Continuous drift-diffusion models are routinely used to optimize organic semiconducting devices. Material properties are incorporated into these models via dependencies of diffusion constants, mobilities, and injection barriers on temperature, charge density, and external field. The respective expressions are often provided by the generic Gaussian disorder models, parametrized on experimental data. We show that this approach is limited by the fixed range of applicability of analytic expressions as well as approximations inherent to lattice models. To overcome these limitations we propose a scheme which first tabulates simulation results performed on small-scale off-lattice models, corrects for finite size effects, and then uses the tabulated mobility values to solve the drift-diffusion equations. The scheme is tested on DPBIC, a state of the art hole conductor for organic light emitting diodes. We find a good agreement between simulated and experimentally measured current-voltage characteristics for different film thicknesses and temperatures. PMID- 26267616 TI - Associations between the Genetic Polymorphisms of Osteopontin Promoter and Susceptibility to Cancer in Chinese Population: A Meta-Analysis. AB - BACKGROUND AND AIM: Several studies have been conducted to examine the associations between osteopontin (OPN) promoter gene SPP1 polymorphisms with human cancers in Chinese population, but the results remain inconsistent. The aim of this meta-analysis is to clarify the associations between SPP1 polymorphisms and cancer susceptibility. METHODS: All eligible case-control studies published up to March 2015 were identified by searching PubMed, Web of Science, Embase, and Cochrane Library without language restrictions. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated using fixed- or random-effect model. RESULTS: A total of 11 case-control studies were included; of those, there were eleven studies (3130 cases and 3828 controls) for -443T>C polymorphism, ten studies (3019 cases and 3615 controls) for -156G>GG polymorphism, eight studies (2258 cases and 2846 controls) for -66T>G polymorphism. Overall, no evidence indicated that the -443 T>C polymorphism was associated with cancer risk (OR = 0.93, 95%CI 0.62-1.38 for dominant model, OR = 1.06, 95%CI 0.73-1.55 for recessive model, OR = 0.88, 95%CI 0.62-1.26 for CT vs TT model, OR = 1.03, 95%CI 0.61-1.73 for CC vs TT model). While, a significantly increase risk was found for -156 G>GG polymorphism (OR = 1.22, 95%CI 1.10-1.35 for dominant model, OR = 1.25, 95%CI 1.10-1.41 for recessive model, OR = 1.18, 95%CI 1.06-1.32 for GGG vs GG model, OR = 1.35, 95%CI 1.09-1.68 for GGGG vs GG model). For -66T>G polymorphism, we found a decrease risk of cancer (OR = 0.84, 95% CI 0.71-0.98 for dominant model), but this result changed (OR = 0.93, 95% CI 0.77-1.12 for dominant model) when we excluded a study. CONCLUSION: This meta-analysis suggests that in Chinese population the -156G>GG polymorphism of SPP1 might be a risk factor for human cancers, while -443T>C mutation is not associated with cancer risk. For -66T>G polymorphism, it may be a protective factor for human cancers. PMID- 26267618 TI - The Paternalism Preference--Choosing Unshared Decision Making. PMID- 26267619 TI - Innovation as Discipline, Not Fad. PMID- 26267620 TI - Differential Taxes for Differential Risks--Toward Reduced Harm from Nicotine Yielding Products. PMID- 26267621 TI - High HLA-DP Expression and Graft-versus-Host Disease. AB - BACKGROUND: Transplantation of hematopoietic cells from unrelated donors can cure blood disorders but carries a significant risk of acute graft-versus-host disease (GVHD). The risk is higher when the recipient and donor are HLA-DPB1-mismatched, but the mechanisms leading to GVHD are unknown. The HLA-DPB1 regulatory region variant rs9277534 is associated with HLA-DPB1 expression. We tested the hypothesis that the GVHD risk correlates with the rs9277534 allele linked to the mismatched HLA-DPB1 in the recipient. METHODS: We genotyped rs9277534 in 3505 persons to define rs9277534-DPB1 haplotypes. Among 1441 recipients of transplants from HLA-A,B,C,DRB1,DQB1-matched unrelated donors with only one HLA-DPB1 mismatch, linkage of the rs9277534 A and G alleles to the mismatched HLA-DPB1 was determined. HLA-DPB1 expression was assessed by means of a quantitative polymerase-chain-reaction assay. The risk of acute GVHD among recipients whose mismatched HLA-DPB1 allele was linked to rs9277534G (high expression) was compared with the risk among recipients whose mismatched HLA-DPB1 allele was linked to rs9277534A (low expression). RESULTS: The mean HLA-DPB1 expression was lower with rs9277534A than with rs9277534G. Among recipients of transplants from donors with rs9277534A-linked HLA-DPB1, the risk of acute GVHD was higher for recipients with rs9277534G-linked HLA-DPB1 mismatches than for recipients with rs9277534A-linked HLA-DPB1 mismatches (hazard ratio, 1.54; 95% confidence interval [CI], 1.25 to 1.89; P<0.001), as was the risk of death due to causes other than disease recurrence (hazard ratio, 1.25; 95% CI, 1.00 to 1.57; P=0.05). CONCLUSIONS: The risk of GVHD associated with HLA-DPB1 mismatching was influenced by the HLA-DPB1 rs9277534 expression marker. Among recipients of HLA-DPB1 mismatched transplants from donors with the low-expression allele, recipients with the high-expression allele had a high risk of GVHD. (Funded by the National Institutes of Health and others.). PMID- 26267625 TI - IMAGES IN CLINICAL MEDICINE. Constipation Associated with a Lipoma. PMID- 26267624 TI - Ischemic Limb Gangrene with Pulses. PMID- 26267626 TI - CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 25-2015. An 8-Year-Old Girl with a Chest-Wall Mass and a Pleural Effusion. PMID- 26267627 TI - Immunogenetics of HLA-DP--A New View of Permissible Mismatches. PMID- 26267628 TI - Cardiac Troponin and Risk Stratification in Ischemic Heart Disease. PMID- 26267623 TI - A Randomized Trial of Intrapartum Fetal ECG ST-Segment Analysis. AB - BACKGROUND: It is unclear whether using fetal electrocardiographic (ECG) ST segment analysis as an adjunct to conventional intrapartum electronic fetal heart rate monitoring modifies intrapartum and neonatal outcomes. METHODS: We performed a multicenter trial in which women with a singleton fetus who were attempting vaginal delivery at more than 36 weeks of gestation and who had cervical dilation of 2 to 7 cm were randomly assigned to "open" or "masked" monitoring with fetal ST-segment analysis. The masked system functioned as a normal fetal heart-rate monitor. The open system displayed additional information for use when uncertain fetal heart-rate patterns were detected. The primary outcome was a composite of intrapartum fetal death, neonatal death, an Apgar score of 3 or less at 5 minutes, neonatal seizure, an umbilical-artery blood pH of 7.05 or less with a base deficit of 12 mmol per liter or more, intubation for ventilation at delivery, or neonatal encephalopathy. RESULTS: A total of 11,108 patients underwent randomization; 5532 were assigned to the open group, and 5576 to the masked group. The primary outcome occurred in 52 fetuses or neonates of women in the open group (0.9%) and 40 fetuses or neonates of women in the masked group (0.7%) (relative risk, 1.31; 95% confidence interval, 0.87 to 1.98; P=0.20). Among the individual components of the primary outcome, only the frequency of a 5 minute Apgar score of 3 or less differed significantly between neonates of women in the open group and those in the masked group (0.3% vs. 0.1%, P=0.02). There were no significant between-group differences in the rate of cesarean delivery (16.9% and 16.2%, respectively; P=0.30) or any operative delivery (22.8% and 22.0%, respectively; P=0.31). Adverse events were rare and occurred with similar frequency in the two groups. CONCLUSIONS: Fetal ECG ST-segment analysis used as an adjunct to conventional intrapartum electronic fetal heart-rate monitoring did not improve perinatal outcomes or decrease operative-delivery rates. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and Neoventa Medical; ClinicalTrials.gov number, NCT01131260.). PMID- 26267629 TI - Taking Patients' Narratives about Clinicians from Anecdote to Science. PMID- 26267630 TI - Primary PCI with or without Thrombectomy. PMID- 26267631 TI - Primary PCI with or without Thrombectomy. PMID- 26267632 TI - Primary PCI with or without Thrombectomy. PMID- 26267633 TI - Primary PCI with or without Thrombectomy. PMID- 26267634 TI - Primary PCI with or without Thrombectomy. PMID- 26267635 TI - Primary PCI with or without Thrombectomy. PMID- 26267622 TI - Troponin and Cardiac Events in Stable Ischemic Heart Disease and Diabetes. AB - BACKGROUND: Cardiac troponin concentrations are used to identify patients who would benefit from urgent revascularization for acute coronary syndromes. We hypothesized that they might be used in patients with stable ischemic heart disease to identify those at high risk for cardiovascular events who might also benefit from prompt coronary revascularization. METHODS: We measured the cardiac troponin T concentration at baseline with a high-sensitivity assay in 2285 patients who had both type 2 diabetes and stable ischemic heart disease and were enrolled in the Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes trial. We tested for an association between the troponin T concentration and a composite end point of death from cardiovascular causes, myocardial infarction, or stroke; we then evaluated whether random assignment to prompt revascularization reduced the rate of the composite end point in patients with an abnormal troponin T concentration (>=14 ng per liter) as compared with those with a normal troponin T concentration (<14 ng per liter). RESULTS: Of the 2285 patients, 2277 (99.6%) had detectable (>=3 ng per liter) troponin T concentrations and 897 (39.3%) had abnormal troponin T concentrations at baseline. The 5-year rate of the composite end point was 27.1% among the patients who had had abnormal troponin T concentrations at baseline, as compared with 12.9% among those who had had normal baseline troponin T concentrations. In models that were adjusted for cardiovascular risk factors, severity of diabetes, electrocardiographic abnormalities, and coronary anatomy, the hazard ratio for the composite end point among patients with abnormal troponin T concentrations was 1.85 (95% confidence interval [CI], 1.48 to 2.32; P<0.001). Among patients with abnormal troponin T concentrations, random assignment to prompt revascularization, as compared with medical therapy alone, did not result in a significant reduction in the rate of the composite end point (hazard ratio, 0.96; 95% CI, 0.74 to 1.25). CONCLUSIONS: The cardiac troponin T concentration was an independent predictor of death from cardiovascular causes, myocardial infarction, or stroke in patients who had both type 2 diabetes and stable ischemic heart disease. An abnormal troponin T value of 14 ng per liter or higher did not identify a subgroup of patients who benefited from random assignment to prompt coronary revascularization. (Funded by the National Institutes of Health and Roche Diagnostics; BARI 2D ClinicalTrials.gov number, NCT00006305.). PMID- 26267636 TI - Antibiotics for Community-Acquired Pneumonia in Adults. PMID- 26267637 TI - Antibiotics for Community-Acquired Pneumonia in Adults. PMID- 26267638 TI - Antibiotics for Community-Acquired Pneumonia in Adults. PMID- 26267639 TI - Antibiotics for Community-Acquired Pneumonia in Adults. PMID- 26267640 TI - Antibiotics for Community-Acquired Pneumonia in Adults. PMID- 26267642 TI - IMAGES IN CLINICAL MEDICINE. Hemoptysis Associated with Paragonimus westermani. PMID- 26267641 TI - Pelvic Inflammatory Disease. PMID- 26267643 TI - INTERACTIVE MEDICAL CASE. A Man with Bizarre Behavior. PMID- 26267644 TI - Transcriptomic Analysis of Paeonia delavayi Wild Population Flowers to Identify Differentially Expressed Genes Involved in Purple-Red and Yellow Petal Pigmentation. AB - Tree peony (Paeonia suffruticosa Andrews) is a very famous traditional ornamental plant in China. P. delavayi is a species endemic to Southwest China that has aroused great interest from researchers as a precious genetic resource for flower color breeding. However, the current understanding of the molecular mechanisms of flower pigmentation in this plant is limited, hindering the genetic engineering of novel flower color in tree peonies. In this study, we conducted a large-scale transcriptome analysis based on Illumina HiSeq sequencing of cDNA libraries generated from yellow and purple-red P. delavayi petals. A total of 90,202 unigenes were obtained by de novo assembly, with an average length of 721 nt. Using Blastx, 44,811 unigenes (49.68%) were found to have significant similarity to accessions in the NR, NT, and Swiss-Prot databases. We also examined COG, GO and KEGG annotations to better understand the functions of these unigenes. Further analysis of the two digital transcriptomes revealed that 6,855 unigenes were differentially expressed between yellow and purple-red flower petals, with 3,430 up-regulated and 3,425 down-regulated. According to the RNA-Seq data and qRT-PCR analysis, we proposed that four up-regulated key structural genes, including F3H, DFR, ANS and 3GT, might play an important role in purple-red petal pigmentation, while high co-expression of THC2'GT, CHI and FNS II ensures the accumulation of pigments contributing to the yellow color. We also found 50 differentially expressed transcription factors that might be involved in flavonoid biosynthesis. This study is the first to report genetic information for P. delavayi. The large number of gene sequences produced by transcriptome sequencing and the candidate genes identified using pathway mapping and expression profiles will provide a valuable resource for future association studies aimed at better understanding the molecular mechanisms underlying flower pigmentation in tree peonies. PMID- 26267645 TI - A Risk Assessment Tool to Predict Sustained PTSD Symptoms Among Women Reporting Abuse. AB - BACKGROUND: Nationally and worldwide, 30% or more of women are likely to have experienced intimate partner violence. Maternal mental health symptoms predict child function. When mothers have sustained posttraumatic stress disorder (PTSD), their children at are risk for growth and developmental delays and poor behavioral outcomes that may adversely affect the course of their lives. While many who experience trauma will recover without intervention, a significant proportion will experience PTSD, with negative consequences for their personal lives and the lives of their families. Early identification of those at high risk for PTSD symptoms will support early interventions to prevent PTSD and its negative consequences. METHODS: This paper describes the development of a tool that can predict PTSD symptoms at 8 months in mothers who are primarily of low socioeconomic status and primarily members of underrepresented groups. The tool consists of four key measures. CONCLUSIONS: Using this tool to identify mothers at high risk for sustained PTSD and entering them into early intervention programs may protect mothers and their children from negative outcomes and promote their health and wellbeing. PMID- 26267648 TI - CO Oxidation Promoted by the Gold Dimer in Au2 VO3 (-) and Au2 VO4 (-) Clusters. AB - Investigations on the reactivity of atomic clusters have led to the identification of the elementary steps involved in catalytic CO oxidation, a prototypical reaction in heterogeneous catalysis. The atomic oxygen species O(.-) and O(2-) bonded to early-transition-metal oxide clusters have been shown to oxidize CO. This study reports that when an Au2 dimer is incorporated within the cluster, the molecular oxygen species O2 (2-) bonded to vanadium can be activated to oxidize CO under thermal collision conditions. The gold dimer was doped into Au2 VO4 (-) cluster ions which then reacted with CO in an ion-trap reactor to produce Au2 VO3 (-) and then Au2 VO2 (-) . The dynamic nature of gold in terms of electron storage and release promotes CO oxidation and O-O bond reduction. The oxidation of CO by atomic clusters in this study parallels similar behavior reported for the oxidation of CO by supported gold catalysts. PMID- 26267649 TI - Ultrasound-targeted microbubble destruction (UTMD) assisted delivery of shRNA against PHD2 into H9C2 cells. AB - Gene therapy has great potential for human diseases. Development of efficient delivery systems is critical to its clinical translation. Recent studies have shown that microbubbles in combination with ultrasound (US) can be used to facilitate gene delivery. An aim of this study is to investigate whether the combination of US-targeted microbubble destruction (UTMD) and polyethylenimine (PEI) (UTMD/PEI) can mediate even greater gene transfection efficiency than UTMD alone and to optimize ultrasonic irradiation parameters. Another aim of this study is to investigate the biological effects of PHD2-shRNA after its transfection into H9C2 cells. pEGFP-N1 or eukaryotic shPHD2-EGFP plasmid was mixed with albumin-coated microbubbles and PEI to form complexes for transfection. After these were added into H9C2 cells, the cells were exposed to US with various sets of parameters. The cells were then harvested and analyzed for gene expression. UTMD/PEI was shown to be highly efficient in gene transfection. An US intensity of 1.5 W/cm2, a microbubble concentration of 300MUl/ml, an exposure time of 45s, and a plasmid concentration of 15MUg/ml were found to be optimal for transfection. UTMD/PEI-mediated PHD2-shRNA transfection in H9C2 cells significantly down regulated the expression of PHD2 and increased expression of HIF-1alpha and downstream angiogenesis factors VEGF, TGF-beta and bFGF. UTMD/PEI, combined with albumin-coated microbubbles, warrants further investigation for therapeutic gene delivery. PMID- 26267650 TI - The physiological response of two green calcifying algae from the Great Barrier Reef towards high dissolved inorganic and organic carbon (DIC and DOC) availability. AB - Increasing dissolved inorganic carbon (DIC) concentrations associated with ocean acidification can affect marine calcifiers, but local factors, such as high dissolved organic carbon (DOC) concentrations through sewage and algal blooms, may interact with this global factor. For calcifying green algae of the genus Halimeda, a key tropical carbonate producer that often occurs in coral reefs, no studies on these interactions have been reported. These data are however urgently needed to understand future carbonate production. Thus, we investigated the independent and combined effects of DIC (pCO2 402 MUatm/ pHtot 8.0 and 996 MUatm/ pHtot 7.7) and DOC (added as glucose in 0 and 294 MUmol L-1) on growth, calcification and photosynthesis of H. macroloba and H. opuntia from the Great Barrier Reef in an incubation experiment over 16 days. High DIC concentrations significantly reduced dark calcification of H. opuntia by 130 % and led to net dissolution, but did not affect H. macroloba. High DOC concentrations significantly reduced daily oxygen production of H. opuntia and H. macroloba by 78 % and 43 %, respectively, and significantly reduced dark calcification of H. opuntia by 70%. Combined high DIC and DOC did not show any interactive effects for both algae, but revealed additive effects for H. opuntia where the combination of both factors reduced dark calcification by 162 % compared to controls. Such species-specific differences in treatment responses indicate H. opuntia is more susceptible to a combination of high DIC and DOC than H. macroloba. From an ecological perspective, results further suggest a reduction of primary production for Halimeda-dominated benthic reef communities under high DOC concentrations and additional decreases of carbonate accretion under elevated DIC concentrations, where H. opuntia dominates the benthic community. This may reduce biogenic carbonate sedimentation rates and hence the buffering capacity against further ocean acidification. PMID- 26267651 TI - Electrostatic Energetics of Bacillus subtilis Ribonuclease P Protein Determined by Nuclear Magnetic Resonance-Based Histidine pKa Measurements. AB - The pKa values of ionizable groups in proteins report the free energy of site specific proton binding and provide a direct means of studying pH-dependent stability. We measured histidine pKa values (H3, H22, and H105) in the unfolded (U), intermediate (I), and sulfate-bound folded (F) states of RNase P protein, using an efficient and accurate nuclear magnetic resonance-monitored titration approach that utilizes internal reference compounds and a parametric fitting method. The three histidines in the sulfate-bound folded protein have pKa values depressed by 0.21 +/- 0.01, 0.49 +/- 0.01, and 1.00 +/- 0.01 units, respectively, relative to that of the model compound N-acetyl-l-histidine methylamide. In the unliganded and unfolded protein, the pKa values are depressed relative to that of the model compound by 0.73 +/- 0.02, 0.45 +/- 0.02, and 0.68 +/- 0.02 units, respectively. Above pH 5.5, H22 displays a separate resonance, which we have assigned to I, whose apparent pKa value is depressed by 1.03 +/- 0.25 units, which is ~0.5 units more than in either U or F. The depressed pKa values we observe are consistent with repulsive interactions between protonated histidine side chains and the net positive charge of the protein. However, the pKa differences between F and U are small for all three histidines, and they have little ionic strength dependence in F. Taken together, these observations suggest that unfavorable electrostatics alone do not account for the fact that RNase P protein is intrinsically unfolded in the absence of ligand. Multiple factors encoded in the P protein sequence account for its IUP property, which may play an important role in its function. PMID- 26267652 TI - Social exclusion changes histone modifications H3K4me3 and H3K27ac in liver tissue of wild house mice. AB - Wild house mice form social hierarchies with aggressive males defending territories, in which females, young mice and submissive adult males share nests. In contrast, socially excluded males are barred from breeding groups, have numerous bite wounds and patches of thinning fur. Since their feeding times are often disrupted, we investigated whether social exclusion leads to changes in epigenetic marks of metabolic genes in liver tissue. We used chromatin immunoprecipitation and quantitative PCR to measure enrichment of two activating histone marks at 15 candidate loci. The epigenetic profiles of healthy males sampled from nest boxes differed significantly from the profiles of ostracized males caught outside of nests and showing bite wounds indicative of social exclusion. Enrichment of histone-3 lysine-4 trimethylation (H3K4me3) changed significantly at genes Cyp4a14, Gapdh, Nr3c1, Pck1, Ppara, and Sqle. Changes at histone-3 lysine-27 acetylation (H3K27ac) marks were detected at genes Fasn, Nr3c1, and Plin5. A principal components analysis separated the socialized from the ostracized mice. This was independent of body weight for the H3K4me3 mark, and partially dependent for H3K27ac. There was no separation, however, between healthy males that had been sampled from two different nests. A hierarchical cluster analysis also separated the two phenotypes, which was independent of body weight for both markers. Our study shows that a period of social exclusion during adult life leads to quantitative changes in histone modification patterns in mouse liver tissue. Similar epigenetic changes might occur during the development of stress-induced metabolic disorders in humans. PMID- 26267653 TI - Anomalous High-Energy Waterfall-Like Electronic Structure in 5 d Transition Metal Oxide Sr2IrO4 with a Strong Spin-Orbit Coupling. AB - The low energy electronic structure of Sr2IrO4 has been well studied and understood in terms of an effective Jeff = 1/2 Mott insulator model. However, little work has been done in studying its high energy electronic behaviors. Here we report a new observation of the anomalous high energy electronic structure in Sr2IrO4. By taking high-resolution angle-resolved photoemission measurements on Sr2IrO4 over a wide energy range, we have revealed for the first time that the high energy electronic structures show unusual nearly-vertical bands that extend over a large energy range. Such anomalous high energy behaviors resemble the high energy waterfall features observed in the cuprate superconductors. While strong electron correlation plays an important role in producing high energy waterfall features in the cuprate superconductors, the revelation of the high energy anomalies in Sr2IrO4, which exhibits strong spin-orbit coupling and a moderate electron correlation, points to an unknown and novel route in generating exotic electronic excitations. PMID- 26267654 TI - Seroprevalence of IgG1 and IgG4 class antibodies against Mycobacterium avium subsp. paratuberculosis in Japanese population. AB - Mycobacterium avium subsp. paratuberculosis (MAP) is the established causative agent of Johne's disease in cattle and other ruminants, and it has also been speculated to be a putative etiological agent of several human autoimmune diseases. It is acknowledged that dairy products deriving from infected animals play a role (could be vehicles) in exposing humans to MAP. MAP could stimulate the human immune system by means of their complex antigen (in the case of lipids, multivalent antigens) and may modulate it, acting as adjuvant molecules such as Freund's complete adjuvant. The immune system might be abnormally stimulated by the constant presence of MAP antigens (for example, in the dairy products), and this might be particularly relevant in genetically predisposed individuals. However, there is limited understanding about the current human exposure to MAP. The present study analyzed the antibody recognition profile of MAP lipophilic antigens in a cohort of 126 healthy Japanese. We measured the serum levels of total immunoglobulin G (IgG) and subclasses targeting MAP surface antigens through ethanol vortex indirect enzyme-linked immunosorbent assay (EVELISA) by using serum absorbed with Mycobacterium phlei. Elevated IgG (especially IgG1 and IgG4) responses were observed in 14% of the sera. To assess the specificity of EVELISA, the same samples were analyzed by means of a commercially available Johnelisa II kit. It was noteworthy that a high degree of correlation was observed when comparing the two methodologies (rs=0.7, p<0.0001). Moreover, in order to investigate the specificity of the binding, inhibition assay experiments were carried out also searching for antibodies against Bacillus Calmette-Guerin antigens, but no cross-reaction was observed. The result obtained represents the first evidence implying that the Japanese population is exposed to MAP, and additionally the existence of a foodborne chain of exposure that transmits MAP antigens to humans. PMID- 26267655 TI - Controlling tunnelling in methane loss from acetone ions by deuteration. AB - Energetic acetone cations decay by methane or methyl radical loss. Although the methane-loss barrier to form the ketene cation is higher and the activation entropy is lower, it has a significant branching ratio at low energies thanks to quantum tunnelling. H-atom tunnelling can be selectively quenched and the methane loss channel suppressed quantitatively by deuteration. PMID- 26267656 TI - A Novel Method for Inducing Amastigote-To-Trypomastigote Transformation In Vitro in Trypanosoma cruzi Reveals the Importance of Inositol 1,4,5-Trisphosphate Receptor. AB - BACKGROUND: Trypanosoma cruzi is a parasitic protist that causes Chagas disease, which is prevalent in Latin America. Because of the unavailability of an effective drug or vaccine, and because about 8 million people are infected with the parasite worldwide, the development of novel drugs demands urgent attention. T. cruzi infects a wide variety of mammalian nucleated cells, with a preference for myocardial cells. Non-dividing trypomastigotes in the bloodstream infect host cells where they are transformed into replication-capable amastigotes. The amastigotes revert to trypomastigotes (trypomastigogenesis) before being shed out of the host cells. Although trypomastigote transformation is an essential process for the parasite, the molecular mechanisms underlying this process have not yet been clarified, mainly because of the lack of an assay system to induce trypomastigogenesis in vitro. METHODOLOGY/PRINCIPAL FINDINGS: Cultivation of amastigotes in a transformation medium composed of 80% RPMI-1640 and 20% Grace's Insect Medium mediated their transformation into trypomastigotes. Grace's Insect Medium alone also induced trypomastigogenesis. Furthermore, trypomastigogenesis was induced more efficiently in the presence of fetal bovine serum. Trypomastigotes derived from in vitro trypomastigogenesis were able to infect mammalian host cells as efficiently as tissue-culture-derived trypomastigotes (TCT) and expressed a marker protein for TCT. Using this assay system, we demonstrated that T. cruzi inositol 1,4,5-trisphosphate receptor (TcIP3R)-an intracellular Ca2+ channel and a key molecule involved in Ca2+ signaling in the parasite-is important for the transformation process. CONCLUSION/SIGNIFICANCE: Our findings provide a new tool to identify the molecular mechanisms of the amastigote-to-trypomastigote transformation, leading to a new strategy for drug development against Chagas disease. PMID- 26267657 TI - Characterization of the MUC1-C Cytoplasmic Domain as a Cancer Target. AB - Mucin 1 (MUC1) is a heterodimeric protein that is aberrantly expressed in diverse human carcinomas and certain hematologic malignancies. The oncogenic MUC1 transmembrane C-terminal subunit (MUC1-C) functions in part by transducing growth and survival signals from cell surface receptors. However, little is known about the structure of the MUC1-C cytoplasmic domain as a potential drug target. Using methods for structural predictions, our results indicate that a highly conserved CQCRRK sequence, which is adjacent to the cell membrane, forms a small pocket that exposes the two cysteine residues for forming disulfide bonds. By contrast, the remainder of the MUC1-C cytoplasmic domain has no apparent structure, consistent with an intrinsically disordered protein. Our studies thus focused on targeting the MUC1 CQCRRK region. The results show that L- and D-amino acid CQCRRK-containing peptides bind directly to the CQC motif. We further show that the D-amino acid peptide, designated GO-203, blocks homodimerization of the MUC1 C cytoplasmic domain in vitro and in transfected cells. Moreover, GO-203 binds directly to endogenous MUC1-C in breast and lung cancer cells. Colocalization studies further demonstrate that GO-203 predominantly binds to MUC1-C at the cell membrane. These findings support the further development of agents that target the MUC1-C cytoplasmic domain CQC motif and thereby MUC1-C function in cancer cells. PMID- 26267658 TI - In Vitro Activity of Epigallocatechin Gallate and Quercetin Alone and in Combination versus Clinical Isolates of Methicillin-Resistant Staphylococcus aureus. AB - Topical infections can become life threatening in immunocompromised patients. However, fewer treatments are available as multi-drug-resistant bacteria become more common. The natural compounds epigallocatechin gallate (1) and quercetin (2) alone and in combination were tested as potential antimicrobial clinical therapies. Strong antimicrobial activity was produced by 1 alone against methicillin-resistant Staphylococcus aureus, and activity was significantly increased in the presence of 2. A synergistic interaction was observed between the two compounds. Kill kinetics indicate the combination is bactericidal over 24 h. PMID- 26267659 TI - Stevens Johnson Syndrome and Toxic Epidermal Necrolysis: Maternal and Foetal Outcomes in Twenty-Two Consecutive Pregnant HIV Infected Women. AB - INTRODUCTION: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) form a spectrum of a rare and life-threatening cutaneous drug reaction. SJS/TEN in pregnancy poses largely unknown risk factors and outcomes for both the mother and foetus compared to the general population. METHODS: We conducted a study of consecutive pregnant women admitted to single tertiary referral centre in South Africa with SJS/TEN over a 3 year period. They were all managed by the same medical team using the same protocols. We evaluated their underlying illnesses, offending drugs and the course of pregnancy and outcomes to determine factors influencing maternal and foetal outcomes. RESULTS: We identified twenty-two women who developed SJS/TEN while pregnant, all of them HIV-infected. Their median age was 29 years. The majority 16/22 (73%) had SJS, the milder variant of the disease affecting < 10% body surface area. Nevirapine was the offending drug in 21/22 (95%) cases. All 22 of the mothers survived with 3/22 (14%) developing postpartum sepsis. Pregnancy outcomes were known in 18/22 women and 9/18 (50%) babies were delivered by caesarean section. There were 2 foetal deaths at 21 and 31 weeks respectively and both were associated with post-partum sepsis. Postnatal complications occurred in 5 cases, 3 involving the respiratory system and the other two being low birth weight deliveries. Eight placentae and one foetus were sent for histology and none showed macroscopic or microscopic features of SJS/TEN. On follow-up, only 12/20 children were tested for HIV at 6 weeks post delivery and none of them were HIV-infected. All had received prophylactic ARVs including nevirapine. CONCLUSIONS: TEN, the severe form of the disease, was associated with poorer foetal outcomes. SJS/TEN-associated mortality is not increased in HIV-infected pregnant women. Maternal SJS/TEN does not seem to commonly manifest in the foetus. PMID- 26267660 TI - Detection of retinal changes in idiopathic Parkinson's disease using high resolution optical coherence tomography and heidelberg retina tomography. AB - PURPOSE: The study was performed to analyse the retina of patients with Parkinson's disease (PD) for morphological changes compared to healthy controls (HC) using spectral-domain optical coherence tomography (SD-OCT) and confocal scanning laser ophthalmoscopy. METHODS: We enrolled 108 patients with idiopathic PD and 165 HC. All study participants underwent an ophthalmological examination to exclude ophthalmological disorder potentially interfering with the retinal analyses. Peripapillary retinal nerve fibre layer (RNFL) thickness and macular thickness and volume were measured by a SD-OCT device (Heidelberg Spectralis((r)) ). Stereometric parameters of the optic disc were acquired by Heidelberg Retina Tomograph (HRT III). RESULTS: The RNFL thickness did not significantly differ between patients with PD and HC. The thickness of the central minimum and the centre of the macular area were significantly reduced in patients with PD, while the total macular volume did not significantly differ between the groups. Furthermore, we noted an inverse correlation between the central minimum thickness and the disease severity (assessed by the Hoehn and Yahr scale). HRT data showed no significant differences. CONCLUSION: The HRT device and the RNFL measurements of the SD-OCT did not prove to be a clinically valid diagnostic tool to distinguish eyes of patients with PD and HC. However, the macular region and especially the foveola (central minimum) with the highest density of photoreceptor cells seem to be more sensitive and might be potential biomarkers. PMID- 26267661 TI - Voxel-Wise Perfusion Assessment in Cerebral White Matter with PCASL at 3T; Is It Possible and How Long Does It Take? AB - PURPOSE: To establish whether reliable voxel-wise assessment of perfusion in cerebral white matter (WM) is possible using arterial spin labeling (ASL) at 3T in a cohort of healthy subjects. MATERIALS AND METHODS: Pseudo-continuous ASL (PCASL) with background suppression (BS) optimized for WM measurements was performed at 3T in eight healthy male volunteers aged 25-41. Four different labeling schemes were evaluated by varying the labeling duration (LD) and post labeling delay (PLD). Eight slices with voxel dimension 3.75x3.75x5 mm3 were acquired from the anterosuperior aspect of the brain, and 400 image/control pairs were collected for each run. Rigid head immobilization was applied using individually fitted thermoplastic masks. For each voxel in the resulting ASL time series, the time needed to reach a 95% significance level for the ASL signal to be higher than zero (paired t-test), was estimated. RESULTS: The four protocols detected between 88% and 95% (after Bonferroni correction: 75% and 88%) of WM voxels at 95% significance level. In the most efficient sequence, 80% was reached after 5 min and 95% after 53 min (after Bonferroni correction 40% and 88% respectively). For all protocols, the fraction of significant WM voxels increased in an asymptotic fashion with increasing scan time. A small subgroup of voxels was shown to not benefit at all from prolonged measurement. CONCLUSION: Acquisition of a significant ASL signal from a majority of WM voxels is possible within clinically acceptable scan times, whereas full coverage needs prohibitively long scan times, as a result of the asymptotic trajectory. PMID- 26267662 TI - Long-term objective esthetic outcome after breast-conserving therapy. AB - The prediction of unfavorable long-term esthetic outcome (AO) is important for patient consultation. We aimed to analyze variables characterizing the improvement and impairment of AO over time after breast-conserving surgery. A subgroup of a prospective, monocenter cohort study was analyzed to evaluate the results of the BCCT.core software (Breast Cancer Conservative Treatment.cosmetic results) which was used to objectively assess the AO before (n = 356), shortly after (n = 294) and in median 3 years after surgery (n = 356). We analyzed potential influencing factors (such as body mass index, (y)pT-stage, weight of resected specimen, etc.) on the AO using logistic regression analyses (n = 256). Finally, we tried to characterize groups of patients with improving or impaired AO over time (n = 294). Predictors for an unfavorable AO were an axillary lymphadenectomy (OR = 4.05), a tumor in the 12 o'clock position (OR = 2.22), a tumor stage larger or equal to (y)pT2 stage (OR = 2.11), and a surgical specimen weight >75 g (OR = 2.71). Patients with lower specimen weight were more likely to improve in the long-term follow-up (p = 0.018), whereas patients with a higher (y)pT-stage tended to become impaired with time. Although overall AO decreased over time, nearly half of the patients with an unfavorable AO shortly after surgery improved in the long-term follow-up. Predictors of unfavorable AO can be used in patient consultation preoperatively to prepare them for the postsurgical period and/or to recommend surgical alternatives (e.g., more complex oncoplastic techniques). Knowledge of improvement and impairment may help patients and physicians in the postsurgical consultation setting. PMID- 26267663 TI - Navigation surgery for intraoperative sentinel lymph node detection using Indocyanine green (ICG) fluorescence real-time imaging in breast cancer. AB - A new sensitive fluorescence imaging system was developed for the real-time identification of sentinel lymph nodes (SLNs) in patients with early breast cancer. The purpose of this study was to evaluate the utility of a color charge coupled device camera system for the intraoperative detection of SLNs and to determine its clinical efficacy and sensitivity in patients with operable breast cancer. We assessed a total of 168 patients diagnosed with or suspected of having early-stage breast cancer without metastasis in SLNs. The intraoperative detection of SLNs was performed using the conventional Indigo Carmine dye (indigotindisulfonate sodium) technique combined with a new Indocyanine green (ICG) imaging system (HyperEye Medical System: HEMS, MIZUHO IKAKOGYO, Japan) to map SLNs, in which the lymphatic vessels and SLNs were visualized transcutaneously with illuminating ICG fluorescence. Between January 2012 and May 2013, SLNs were successfully identified in all 168 patients (detection rate: 100%). By histopathology, the sensitivity was 93.8% for the detection of the metastatic involvement of SLNs (15 of 16 nodal-positive patients). After a median follow-up of 30.5 months, none of the patients presented with axillary recurrence. These results suggest that the HEMS imaging system is a feasible and effective method for the detection of SLNs in breast cancer. Furthermore, the HEMS device permitted the transcutaneous visualization of lymphatic vessels under light conditions, thus facilitating the identification and detection of SLNs without affecting the surgical procedure, together with a high sensitivity and specificity. PMID- 26267664 TI - Measurement of lipid accumulation in Chlorella vulgaris via flow cytometry and liquid-state 1H NMR spectroscopy for development of an NMR-traceable flow cytometry protocol. AB - In this study, we cultured Chlorella vulgaris cells with a range of lipid contents, induced via nitrogen starvation, and characterized them via flow cytometry, with BODIPY 505/515 as a fluorescent lipid label, and liquid-state 1H NMR spectroscopy. In doing so, we demonstrate the utility of calibrating flow cytometric measurements of algal lipid content using triacylglyceride (TAG, also known as triacylglycerol or triglyceride) content per cell as measured via quantitative 1H NMR. Ensemble-averaged fluorescence of BODIPY-labeled cells was highly correlated with average TAG content per cell measured by bulk NMR, with a linear regression yielding a linear fit with r2 = 0.9974. This correlation compares favorably to previous calibrations of flow cytometry protocols to lipid content measured via extraction, and calibration by NMR avoids the time and complexity that is generally required for lipid quantitation via extraction. Flow cytometry calibrated to a direct measurement of TAG content can be used to investigate the distribution of lipid contents for cells within a culture. Our flow cytometry measurements showed that Chlorella vulgaris cells subjected to nitrogen limitation exhibited higher mean lipid content but a wider distribution of lipid content that overlapped the relatively narrow distribution of lipid content for replete cells, suggesting that nitrogen limitation induces lipid accumulation in only a subset of cells. Calibration of flow cytometry protocols using direct in situ measurement of TAG content via NMR will facilitate rapid development of more precise flow cytometry protocols, enabling investigation of algal lipid accumulation for development of more productive algal biofuel feedstocks and cultivation protocols. PMID- 26267665 TI - Regional Distribution and Evolution of Gray Matter Damage in Different Populations of Multiple Sclerosis Patients. AB - BACKGROUND: Both gray-matter (GM) atrophy and lesions occur from the earliest stages of Multiple Sclerosis (MS) and are one of the major determinants of long term clinical outcomes. Nevertheless, the relationship between focal and diffuse GM damage has not been clarified yet. Here we investigate the regional distribution and temporal evolution of cortical thinning and how it is influenced by the local appearance of new GM lesions at different stages of the disease in different populations of MS patients. METHODS: We studied twenty MS patients with clinically isolated syndrome (CIS), 27 with early relapsing-remitting MS (RRMS, disease duration <5 years), 29 with late RRMS (disease duration >= 5 years) and 20 with secondary-progressive MS (SPMS). The distribution and evolution of regional cortical thickness and GM lesions were assessed during 5-year follow-up. RESULTS: The results showed that new lesions appeared more frequently in hippocampus and parahippocampal gyri (9.1%), insula (8.9%), cingulate cortex (8.3%), superior frontal gyrus (8.1%), and cerebellum (6.5%). The aforementioned regions showed the greatest reduction in thickness/volume, although (several) differences were observed across subgroups. The correlation between the appearance of new cortical lesions and cortical thinning was stronger in CIS (r2 = 50.0, p<0.001) and in early RRMS (r2 = 52.3, p<0.001), compared to late RRMS (r2 = 25.5, p<0.001) and SPMS (r2 = 6.3, p = 0.133). CONCLUSIONS: We conclude that GM atrophy and lesions appear to be different signatures of cortical disease in MS having in common overlapping spatio-temporal distribution patterns. However, the correlation between focal and diffuse damage is only moderate and more evident in the early phase of the disease. PMID- 26267666 TI - Improved clinical course of autologous skeletal myoblast sheet (TCD-51073) transplantation when compared to a propensity score-matched cardiac resynchronization therapy population. AB - We recently reported a multi-center, single-arm, phase II study that evaluated the efficacy and safety of autologous skeletal myoblast sheet (TCD-51073) transplantation. The advantage of this procedure over a control group has not yet been analyzed. Seven patients with advanced heart failure due to ischemic etiology (TCD-51073 group, New York Heart Association (NYHA) class III; left ventricular ejection fraction (LVEF) <35 %) refractory to optimal medical and coronary revascularization therapy, received TCD-51073 at 3 study centers between 2012 and 2013 with a 2-year follow-up period. As previously reported, 112 patients received cardiac resynchronization therapy (CRT) with follow-up at the University of Tokyo Hospital between 2007 and 2014. Of them, 21 patients were selected for the control group by propensity score matching. No significant difference in baseline variables between the groups was observed. LVEF and NYHA class improved significantly in the TCD-51073 group during the 6-month study period (p < 0.05). During the 2-year follow-up, 7 patients (33 %) in the CRT group and no patient in the TCD-51073 group died due to cardiac disease or received VAD implantation (p = 0.128 by the log-rank test). In conclusion, transplantation of TCD-51073 is clinically advantageous in facilitating LV reverse remodeling, improving HF symptoms, and preventing cardiac death in patients with ischemic etiology when compared to background-matched patients receiving CRT. PMID- 26267667 TI - Reducing Human-Tsetse Contact Significantly Enhances the Efficacy of Sleeping Sickness Active Screening Campaigns: A Promising Result in the Context of Elimination. AB - BACKGROUND: Control of gambiense sleeping sickness, a neglected tropical disease targeted for elimination by 2020, relies mainly on mass screening of populations at risk and treatment of cases. This strategy is however challenged by the existence of undetected reservoirs of parasites that contribute to the maintenance of transmission. In this study, performed in the Boffa disease focus of Guinea, we evaluated the value of adding vector control to medical surveys and measured its impact on disease burden. METHODS: The focus was divided into two parts (screen and treat in the western part; screen and treat plus vector control in the eastern part) separated by the Rio Pongo river. Population census and baseline entomological data were collected from the entire focus at the beginning of the study and insecticide impregnated targets were deployed on the eastern bank only. Medical surveys were performed in both areas in 2012 and 2013. FINDINGS: In the vector control area, there was an 80% decrease in tsetse density, resulting in a significant decrease of human tsetse contacts, and a decrease of disease prevalence (from 0.3% to 0.1%; p=0.01), and an almost nil incidence of new infections (<0.1%). In contrast, incidence was 10 times higher in the area without vector control (>1%, p<0.0001) with a disease prevalence increasing slightly (from 0.5 to 0.7%, p=0.34). INTERPRETATION: Combining medical and vector control was decisive in reducing T. b. gambiense transmission and in speeding up progress towards elimination. Similar strategies could be applied in other foci. PMID- 26267669 TI - Dense Deposition of Gold Nanoclusters Utilizing a Porphyrin/Inorganic Layered Material Complex as the Template. AB - We examined the deposition of gold clusters through the reduction of a gold precursor sensitized by nonaggregated, assembled porphyrin molecules on an inorganic layered material surface in order to develop a novel strategy for constructing assemblies of gold clusters. Visible light irradiation on nonaggregated, assembled porphyrin on the inorganic surface in the presence of the gold precursor and an electron donor induced the deposition of gold NPs on the surface of the inorganic layered material. Uniform gold clusters, with an average diameter of 1.5 nm, were deposited on the surface without aggregation. The average interparticle distance between adjacent gold clusters (center to center) was 2.3 nm, which agrees well with the average intermolecular distance of the nonaggregated, assembled porphyrin molecules on the inorganic surface. Thus, the generated gold clusters appear to reflect the nonaggregated, assembled structure of the porphyrin molecules on the inorganic surface. This method, termed the photosensitized template reduction (PTR) method, is a useful and novel technique for the deposition of metal nanoparticles on the surfaces of supporting materials. PMID- 26267668 TI - Parents' and professionals' perceptions on causes and treatment options for Autism Spectrum Disorders (ASD) in a multicultural context on the Kenyan Coast. AB - OBJECTIVE: To explore parents' and professionals' perceived causes and treatment of Autism Spectrum Disorders (ASD) on the Kenyan Coast. METHODS: In-depth interviews and focus group discussions using guiding questions were utilized in data collection. One hundred and three participants, who included parents of children with ASD, special needs teachers, clinicians, and social workers from diverse cultural background, participated in this study. The interviews and focus groups were recorded, transcribed verbatim and then translated to English. Themes were generated using content analysis. RESULTS: Preternatural causes were mentioned and included evil spirits, witchcraft, and curses. Biomedical causes comprised infections, drug abuse, birth complications, malnutrition, and genetic related problems. Treatment varied from traditional and spiritual healing to modern treatment in health facilities, and included consultations with traditional healers, offering prayers to God, and visits to hospitals. CONCLUSIONS: The results suggest that regardless of cultural backgrounds, people on the Kenyan Coast have similar views on perceived causes and treatment of ASD. These findings provide valuable conceptual understanding for professionals when planning and implementing community based rehabilitation interventions targeting children with ASD within a local context. PMID- 26267670 TI - Intraoperative and surgical specimen (ex vivo) ultrasound in the assessment of margins at partial nephrectomy. AB - PURPOSE: To correlate the accuracy of intraoperative and surgical specimen (ex vivo) ultrasound (US) with pathological margin status at partial nephrectomy. MATERIALS AND METHODS: Patients undergoing partial nephrectomy for T1 renal tumours in the period May 2010-January 2014 at a single institution who had intraoperative specimen US were included. PN was performed by standardised technique with intraoperative tumour localisation. Following excision, surgical specimen (ex vivo) US was performed and the margin status was compared to the final histopathological analysis. The specificity of US to identify margin status was calculated as was the correlation between the ultrasonographic and final pathological margin. RESULTS: Forty-five patients were included (median age 61 years). Mean tumour size was 28.1 +/- 10 mm, and 89 % were renal cell carcinomas with the remainder being oncocytomas. Forty-four cases had negative surgical margins on pathological analysis, and US had a specificity of 100 %. There was a strong correlation between the margin as measured on US and final analysis (Pearson's r = 0.86, p < 0.001). CONCLUSION: Results show that intraoperative, surgical specimen (ex vivo) US control of resection margins in patients undergoing PN is feasible and efficient. It represents a promising tool to ensure margin negativity during PN. PMID- 26267671 TI - Li17Sb13S28: A New Lithium Ion Conductor and addition to the Phase Diagram Li2S Sb2S3. AB - Li17Sb13S28 was synthesized by solid-state reaction of stoichiometric amounts of anhydrous Li2S and Sb2S3. The crystal structure of Li17Sb13S28 was determined from dark-red single crystals at room temperature. The title compound crystallizes in the monoclinic space group C2/m (no. 12) with a=12.765(2) A, b=11.6195(8) A, c=9.2564(9) A, beta=119.665(6) degrees , V=1193.0(2) A(3), and Z=4 (data at 20 degrees C, lattice constants from powder diffraction). The crystal structure contains one cation site with a mixed occupation by Li and Sb, and one with an antimony split position. Antimony and sulfur form slightly distorted tetragonal bipyramidal [SbS5E] units (E=free electron pair). Six of these units are arranged around a vacancy in the anion substructure. The lone electron pairs E of the antimony(III) cations are arranged around these vacancies. Thus, a variant of the rock salt structure type with ordered vacancies in the anionic substructure results. Impedance spectroscopic measurements of Li17Sb13S28 show a specific conductivity of 2.9*10(-9) Omega(-1) cm(-1) at 323 K and of 7.9*10(-6) Omega(-1) cm(-1) at 563 K, the corresponding activation energy is EA=0.4 eV below 403 K and EA=0.6 eV above. Raman spectra are dominated by the Sb-S stretching modes of the [SbS5] units at 315 and 341 cm(-1) at room temperature. Differential thermal analysis (DTA) measurements of Li17Sb13S28 indicate peritectic melting at 854 K. PMID- 26267672 TI - Causes and consequences of habitat fragmentation in river networks. AB - Increases in river fragmentation globally threaten freshwater biodiversity. Rivers are fragmented by many agents, both natural and anthropogenic. We review the distribution and frequency of these major agents, along with their effects on connectivity and habitat quality. Most fragmentation research has focused on terrestrial habitats, but theories and generalizations developed in terrestrial habitats do not always apply well to river networks. For example, terrestrial habitats are usually conceptualized as two-dimensional, whereas rivers often are conceptualized as one-dimensional or dendritic. In addition, river flow often leads to highly asymmetric effects of barriers on habitat and permeability. New approaches tailored to river networks can be applied to describe the network-wide effects of multiple barriers on both connectivity and habitat quality. The net effects of anthropogenic fragmentation on freshwater biodiversity are likely underestimated, because of time lags in effects and the difficulty of generating a single, simple signal of fragmentation that applies to all aquatic species. We conclude by presenting a decision tree for managing freshwater fragmentation, as well as some research horizons for evaluating fragmented riverscapes. PMID- 26267673 TI - Phase Transition of Glycolipid Membranes Studied by Coarse-Grained Simulations. AB - Glycolipids are important components of biological membranes. High concentrations of glycolipids are particularly found in lipid rafts, which take part in many physiological phenomena. This different partitioning and interaction pattern of glycolipids in the membrane as compared to those of phospholipids are likely due to their different chemical structures: the polar regions of glycosphingolipids can be even larger than for their hydrophobic moieties, giving rise to a rich conformational landscape. Here we study the influence of glycosphingolipids galactosylceramide (GCER) and monosialotetrahexosylganglioside (GM1) on the structural and thermodynamic properties of a phospholipid (DPPC) bilayer. Using the method of coarse-grained molecular dynamics simulation we show that both glycolipids increase the phase-transition temperature of phospholipid membranes and that the extent of this increase depends on the headgroup size and structure. GM1 shows a strong tendency to form mixed clusters with phospholipids, thereby stabilizing the membrane. In contrast, GCER is dispersed in the membrane. By occupying the interstitial space between phospholipids it causes a tighter packing of the lipids in the membrane. PMID- 26267674 TI - Neurological and neurocognitive functions from intrauterine methylmercury exposure. AB - In the 1950s, large-scale food poisoning caused by methylmercury was identified in Minamata, Japan. Although severe intrauterine exposure cases (ie, congenital Minamata disease patients) are well known, possible impacts of methylmercury exposure in utero among residents, which is likely at lower levels than in congenital Minamata disease patients, are rarely explored. In 2014, the authors examined neurological and neurocognitive functions among 18 exposed participants in Minamata, focusing on fine motor, visuospatial construction, and executive functions. More than half of the participants had some fine motor and coordination difficulties. In addition, several participants had lower performance for neurocognitive function tests (the Rey-Osterrieth Complex Figure test and Keio version of the Wisconsin card sorting test). These deficits imply diffuse brain damage. This study suggests possible neurological and neurocognitive impacts of prenatal exposure to methylmercury among exposed residents of Minamata. PMID- 26267675 TI - Selenium-containing polysaccharides from Ziyang green tea ameliorate high fructose diet induced insulin resistance and hepatic oxidative stress in mice. AB - The present study was designed to evaluate the effects of selenium-containing tea polysaccharides (Se-GTP) from a new variety of selenium-enriched Ziyang green tea against high fructose (HF)-induced insulin resistance and hepatic oxidative stress in mice. Healthy male Kunming mice were fed 20% high fructose water and administered 200, 400 and 800 mg per kg bw Se-GTP for 8 weeks. Mice fed HF in drinking water displayed significant insulin resistance, hepatic steatosis and oxidative stress observed by hyperglycemia and hyperinsulinemia, as well as increases in hepatic non-esterified fatty acid (NEFA) and malonaldehyde (MDA). The administration of Se-GTP at 400 and 800 mg per kg bw significantly improved insulin sensitivity, and reduced liver steatosis and oxidative stress damage, and brought back the antioxidants and hepatic lipids towards near-normal values. In the oral glucose tolerance test, the administration of Se-GTP at 400 and 800 mg per kg bw had reduced plasma glucose concentrations after 30 min of glucose loading in HF-fed mice, suggesting that Se-GTP improved glucose intolerance. Histopathological examination indicated that the impaired pancreatic/hepatic tissues were effectively restored in HF-fed mice following the Se-GTP treatment. This is the first report showing that Se-GTP can ameliorate the high fructose induced insulin resistance and hepatic oxidative injury. PMID- 26267677 TI - CT Dose Optimization in Pediatric Radiology: A Multiyear Effort to Preserve the Benefits of Imaging While Reducing the Risks. AB - The marked increase in radiation exposure from medical imaging, especially in children, has caused considerable alarm and spurred efforts to preserve the benefits but reduce the risks of imaging. Applying the principles of the Image Gently campaign, data-driven process and quality improvement techniques such as process mapping and flowcharting, cause-and-effect diagrams, Pareto analysis, statistical process control (control charts), failure mode and effects analysis, "lean" or Six Sigma methodology, and closed feedback loops led to a multiyear program that has reduced overall computed tomographic (CT) examination volume by more than fourfold and concurrently decreased radiation exposure per CT study without compromising diagnostic utility. This systematic approach involving education, streamlining access to magnetic resonance imaging and ultrasonography, auditing with comparison with benchmarks, applying modern CT technology, and revising CT protocols has led to a more than twofold reduction in CT radiation exposure between 2005 and 2012 for patients at the authors' institution while maintaining diagnostic utility. PMID- 26267676 TI - Platelet abnormalities in nephrotic syndrome. AB - Nephrotic syndrome (NS) is a common kidney disease associated with a significantly increased risk of thrombotic events. Alterations in plasma levels of pro- and anti-coagulant factors are involved in the pathophysiology of venous thrombosis in NS. However, the fact that the risk of both venous and arterial thrombosis is elevated in NS points to an additional role for blood platelets. Increased platelet counts and platelet hyperactivity have been observed in nephrotic children. Platelet hyperaggregability, increased release of active substances, and elevated surface expression of activation-dependent platelet markers have been documented. The mechanisms underlying those platelet alterations are multifactorial and are probably due to changes in plasma levels of platelet-interfering proteins and lipid changes, as a consequence of nephrosis. The causal relationship between platelet alterations seen in NS and the occurrence of thromboembolic phenomena remains unclear. Moreover, the efficiency of prophylactic treatment using antiplatelet agents for the prevention of thrombotic complications in nephrotic patients is also unknown. Thus, antiplatelet medication is currently not generally recommended for routine prophylactic therapy. PMID- 26267678 TI - PERIPAPILLARY RETINAL PIGMENT EPITHELIUM CHANGES IN AGE-RELATED MACULAR DEGENERATION. AB - PURPOSE: To describe peripapillary retinal pigment epithelium changes observed in patients with age-related macular degeneration (AMD) and evaluate their prevalence. METHODS: This study is a prospective, monocentric, comparative case series including 104 consecutive patients with AMD, and 34 patients who are more than 60 years old and consulting for other conditions (control group). Color and fundus autofluorescence images centered on the optic disk were taken and graded by 2 independent readers from 0 to 4: 0, absent; 1, uneven background; 2, focal hyperautofluorescent dots and spots; 3, light reticular pattern; 4, dense reticular pattern. Statistical analysis was performed to correlate the presence of peripapillary retinal pigment epithelium changes with age, sex, and AMD subtype. RESULTS: Peripapillary retinal pigment epithelium changes were observed in 76/104 AMD eyes (73.0%) and were significantly more frequent than in eyes with other conditions (14/34, 41.1%, P = 0.002), whereas groups did not differ for age (P = 0.14). Grade >=2 peripapillary retinal pigment epithelium changes were more frequently observed in patients with AMD than in controls (41.3 vs. 17.6%, P = 0.013). No differences were found between patients with AMD having peripapillary retinal pigment epithelium changes and other patients for age distribution (P = 0.14), sex ratio (P = 0.34), or AMD type (P = 0.57). CONCLUSION: Peripapillary retinal pigment epithelium changes were more frequent in patients with AMD than in controls, and when present, they were of higher grade. Peripapillary retinal pigment epithelium changes significance is not yet understood and needs further evaluation. PMID- 26267679 TI - Predictive modeling of synergistic effects in nanoscale ion track formation. AB - Molecular dynamics techniques in combination with the inelastic thermal spike model are used to study the coupled effects of the inelastic energy loss due to 21 MeV Ni ion irradiation with pre-existing defects in SrTiO3. We determine the dependence on pre-existing defect concentration of nanoscale track formation occurring from the synergy between the inelastic energy loss and the pre-existing atomic defects. We show that the size of nanoscale ion tracks can be controlled by the concentration of pre-existing disorder. This work identifies a major gap in fundamental understanding on the role of defects in electronic energy dissipation and electron-lattice coupling. PMID- 26267680 TI - [Screening and functional analysis of microRNA expression in HPV16-positive squamous carcinoma of the cervix ?in the Uygur of southern Xinjiang]. AB - OBJECTIVE: To explore the differential expression of microRNA (miRNA) in HPV16 positive squamous carcinoma of the cervix in the Uygur of southern Xinjiang and to predict the target genes of the miRNAs.? METHODS: Samples of HPV16-positive squamous carcinoma of the cervix from 5 Uygurs were collected for miRNA microarray assay. The differentially expressed miRNAs were selected for further verification by real-time quantitative RT-PCR. The software, including targetscan, miRwalk, miRanda and pictar, were used to predict the target genes of the verified miRNAs.? RESULTS: Eighteen differentially expressed miRNAs were identified by miRNA microarray assay. The significantly differentially expressed miRNA-138 and miRNA-720 were verified by real-time quantitative RT-PCR. According to the prediction, the target genes for miRNA-138 were EZH2, LYPLA1, ARHGEF3, CLNS1A, EIF4EBP1, GNAI2, LIMK1, RHOC, ROCK2, SLC20A1, TERT, and H2AFX, while for miRNA-720 were EZH2, AGAP2, SPOCK2, FGF14, HNRNPA2B1, QKI, FOXG1, ACVR1B, DNMT3A, EPHB2, LATS2, KRAS, CCND2, NBN, ENAM, AMELX, PRNP, and CALB1.? CONCLUSION: miR 138 and miR-720 are the down-regulated target miRNAs in HPV16-positive squamous carcinoma of the cervix in the Uygur of southern Xinjiang. The common target gene for miR-138 and miR-720 is EZH2, which might be related to cervical squamous carcinoma invasion and metastasis. PMID- 26267681 TI - [Geographical distribution of MTHFR and MTRR gene polymorphisms among the Han women in Zhengzhou city]. AB - OBJECTIVE: To explore the genotype distribution of 5,10-methylenetetrahydrofolate reductase (MTHFR) and 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) among Chinese Han women in Zhengzhou. ? METHODS: A total of 1 253 women were recruited from Zhengzhou city. The genotype of MTHFR C677T, A1298C and MTRR A66G was detected to analyze the distribution of gene polymorphisms and to compare them with the published data from other Han women.? RESULTS: The frequency of the MTHFR 1298CC genotypes (1.3%) in Zhengzhou was lower than that in Xiangtan (4.8%), Yanbian (3.8%), Zhenjiang (3.5%), Jingzhou (3.2%), Kunming (2.7%), Deyang (6.3%), Huizhou (7.2%) and Wulumuqi (3.4%) (all P<0.05). The difference in allele frequency was significant compared with that in Yantai, Yanbian, Wulumuqi, Zhenjiang, Jingzhou, Kunming, Dezhou, Xiangtan or Huizhou (all P<0.05). The frequency of the MTRR 66GG genotypes (5.4%) in Zhengzhou was lower than that in Deyang (8.2%) (P<0.01) and allele frequency between them was significant difference (P<0.05). ? CONCLUSION: The gene polymorphism of MTHFR A1298C and MTRR A66G among the Han women in Zhengzhou is statistically different from that in some regions of China. PMID- 26267682 TI - [Non-thermal effect of high-intensity focused ultrasound on ultrastructure and apoptosis in rabbit hepatic VX2 tumors]. AB - OBJECTIVE: To observe the micromorphological changes of ultrastructure, apoptosis related proteins expression and tumor cell apoptosis after ablation with the high intensity focused ultrasound (HIFU), and to explore the mechanisms responsible for the thermal and non-thermal effect.? METHODS: Forty rabbits with hepatic VX2 tumors were randomly divided into a thermal group (n=20) and a non-thermal group (n=20), and were subjected to HIFU ablation with thermal or non-thermal condition, respectively. Five animals in each group were sacrificed on the 1st, 3rd, 7th or 14th day after the ablation. The changes of ultrastructure, apoptosis related proteins expression and tumor cell apoptosis were detected.? RESULTS: The results of transmission electron microscope (TEM) revealed more severe injury on tissue and cells in the non-thermal group than that in the thermal group. The changes of apoptosis-related proteins expression and tumor cell apoptosis in transient zone were significantly different in comparison with that in the ablated area or peripheral area between the two groups. The expression of vascular endothelial growth factor (VEGF) was at low level on the 1st and 3rd day and elevated gradually on the 7th and 14th day, with no significant difference (all P>0.05). The expression of caspase-3 reached peak on the 3rd day and decreased on the 7th and 14th day. It was significantly higher in the non-thermal group than that in the thermal group on the 3rd and 7th day (all P<0.05). The expression of NF-kappaB was elevated from the 3rd day and reached peak on the 7th day while decreased on the 14th day. There was no significant difference at every time point between the 2 groups (all P>0.05). The apoptosis index in the non thermal group and the thermal group on the 3rd and 7th day were (28.60+/-1.14)% vs (21.80+/-1.92)% and (21.00+/-1.58)% vs (14.80+/-1.48)%, respectively. It was higher in the non-thermal group than that in the thermal group (both P<0.01).? CONCLUSION: Both the thermal and the non-thermal effect of HIFU can induce apoptosis in transient zone, but the latter have a stronger effect. PMID- 26267684 TI - [Changes in CD40 expression in the pallium and hippocampus in epileptic rats]. AB - OBJECTIVE: To investigate the expression of inflammatory molecule CD40 in the pallium and hippocampus of rats after status epilepticus (SE).? METHODS: The expression of CD40 in the pallium, the different areas of hippocampus and the different cells from the lithium-pilocarpine epileptic rats at different time points were examined by immunohistochemistry and double-immunofluorescent labeling.? RESULTS: After SE, CD40 expression was obviously inhibited, especially in hippocampus. CD40 was mainly expressed in the activated microglia. CD40 positive cells reached a peak at the 3rd day and returned to a slightly higher level at the 7th day after SE compared with the level before SE.? CONCLUSION: Elevation of CD40 expression in the activated microglia can promote inflammatory injury of rat's hippocampus, suggesting that CD40 induced-signal pathway is involved in inflammatory injury in the hippocampus after SE. PMID- 26267683 TI - [Fuzheng Huayu recipe promotes the fenestration of capillarization in liver sinusoidal endothelial cells]. AB - OBJECTIVE: To explore the effect of Fuzheng Huayu (FZHY) recipe on the fenestration of capillarization in liver sinusoidal endothelial cells (LSECs).? METHODS: Ten Sprague Dawley (SD) rats were fed with 0.46 g/kg FZHY powder by intragastric administration. Two hours later, a second gavage were given to the rats. The serum from rat heart at 1 hour after second gavage was collected (FZHY group, n=10). Another ten SD rats was administrated with distilled water through the same process and served as the control (control group, n=10). The serum from both groups were separately diluted with Dulbecco minimum essential medium (DMEM) for 10% and served as the culture medium for LSECs. At the different conditions, the vWF and CD31 expressions were detected by immunocytochemistry and Western blot, while the changes of LSECs fenestrae structure were observed under scanning electron microscopy.? RESULTS: 1) Immunocytochemistry and Western blot showed that the vWF and CD31 protein levels were lower in LSECs in the FZHY group than those in the control group. The gray levels of vWF and CD31 protein were 0.548+/ 0.020 and 0.262+/-0.010 in the FZHY group, and 0.845+/-0.090 and 0.383+/-0.010 in the control group respectively, with statistical significant difference (t=5.18, 9.61, both P<0.05). 2) The results from scanning electron microscopy showed that the fenestration of LSECs was closed and almost lost in the control group, but many fenestra appeared in the LSECs in the FZHY group.? CONCLUSION: FZHY recipe can suppress the expression of vWF and CD31, increase the fenestrae on the LSECs surface and reverse the capillarization of LSECs. PMID- 26267685 TI - [Effect of alprostadil on serum level of miRNA-155 ?in uremic patients]. AB - OBJECTIVE: To investigate the serum levels of microRNA-155 (miR-155) and interleukin-6 (IL-6) in uremic dialysis patients and to evaluate the effect of alprostadil (A) on them.? METHODS: A total of 81 chronic kidney disease (CKD) uremic patients were divided into 4 groups: the peritoneal dialysis group (PD group, n=20), the peritoneal dialysis plus alprostadil group (PD+A group, n=20), the hemodialysis group (HD group, n=21), the hemodialysis plus alprostadil group (HD+A group, n=20). Sixteen healthy people were taken as the normal control (NC) group. The peripheral blood of all objects were collected for serum preparation. The expression of miRNA-155 was determined by real-time qPCR and the serum level of IL-6 was measured by ELISA. Experimental and clinical data of all the objects were collected.? RESULTS: Serum levels of miRNA-155 and IL-6 were increased in all dialysis patients groups compared with NC group (P<0.05); miRNA-155 expression in PD+A group was down-regulated compared with PD group or HD group (P<0.05); the levels of IL-6 in PD+A and HD+A group were significantly decreased compared with PD group or HD group (P<0.05). Correlation analysis showed that serum level of miR-155 was positively correlated with the level of IL-6 as well as high-sensitivity C-reactive protein (hs-CRP), while miR-155 was negatively correlated with HDL and albumin (P<0.01). Linear stepwise regression analysis indicated that serum miR-155 was independently associated with albumin and hs CRP.? CONCLUSION: Serum miRNA-155 and IL-6 in uremic dialysis patients were remarkably increased compared to healthy objects. Serum miRNA-155 was positively correlated with the level of IL-6 as well as hs-CRP, while miR-155 was negatively correlated with HDL and albumin. Alprostadil could ameliorate the inflammatory conditions of uremic dialysis patients by inhibition of the IL-6 expression. Serum miRNA-155 may be a novel target for the treatment of uremic dialysis patients. PMID- 26267686 TI - [Association of metabolic syndrome with serum cystatin C in people undergoing health examination]. AB - OBJECTIVE: To investigate the relationship between metabolic syndrome (MetS) and cystatin C in people undergoing healthy examination.? METHODS: A total of 6 783 subjects were analyzed. They were divided into MetS group (n=1 578), metabolic disturbance (MetD) group (n=3 617) and healthy control (HC) group (n=1 588). The general information, anthropometry, blood sample and urine sample were collected for all the subjects. Multiple logistic regression analysis was used to identify risk factors for MetS and analysis of covariance was used to investigate the correlation between the number of metabolic disturbance components and cystatin C.? RESULTS: Compared with the HC group, the level of cystatin C significantly increased in MetS and MetD group; compared with MetD group, the level of cystatin C significantly increased in MetS group (P<0.05). After correction by age, sex, smoking, alcohol intake, menopause, waist circumference, body mass index, blood pressure, plasma cholesterol, fasting plasma glucose, estimated glomerular filtration rate, serum uric acid, microalbuminria, high sensitive C-reaction protein and homocysteine, the cystatin C was closely related with MetS (OR=1.951, 95% CI 1.265-3.009, P<0.05). Similarly, the OR value of risk with MetS was increased with the quartile of cystatin C level (P<0.05). In addition, with the increase in metabolic disturbance components, the level of cystatin C was also increased significantly (P<0.01).? CONCLUSION: Serum cystatin C in our study was significantly associated with MetS. Moreover, the level of cystatin C may be correlated with severity of MetD. PMID- 26267687 TI - [Screening time and schedule for outpatients with acute fatty liver of pregnancy]. AB - OBJECTIVE: To identify the screening time and prepare a screening schedule for outpatients with acute fatty liver of pregnancy (AFLP).? METHODS: AFLP patients who admitted to Xiangya Hospital and the Second Xiangya Hospital, Central South University, Hunan, China between November, 2006 and December, 2013, were retrospectively studied. The diagnosis of 78 AFLP patients met the domestic clinical and laboratory criteria and the Swansea criteria. Clinical and laboratory data obtained on admission were used for analysis. Contrastive analysis was conducted within our data and other large medical centers or general hospitals. ? RESULTS: The difference between domestic clinical and laboratory criteria and Swansea criteria in diagnosing AFLP patients in the 2 hospitals mentioned above was significant (P<0.05). The maternal mortality was 14.10% (11/78) and perinatal mortality was 17.95 % (14/78). The mean gestational age at delivery was 35.6 weeks. Based on the clinical and laboratory data, more than 85% of AFLP patients showed abnormal levels of transaminase, bilirubin, and white blood cells, as well as coagulation dysfunction. Gastrointestinal symptoms, such as abdominal pain and vomiting, jaundice, renal impairment and ascites or bright liver on ultrasound scan, were showed in 50%-85% of AFLP patients. Less than 50% of patients suffered from low blood sugar, high blood ammonia or hepatic encephalopathy.? CONCLUSION: The 34th gestation week might be important time for screening AFLP outpatients. Gastrointestinal symptoms, blood routine, liver function, and coagulant function tests are recommended as the first grade screening indicators. Renal function, blood sugar test, and abdominal ultrasound could be the second grade screening indicators for AFLP outpatients. PMID- 26267688 TI - [Echocardiographic diagnosis for ventricular non-compaction cardiomyopathy in foetus and the pathologically comparative study]. AB - OBJECTIVE: To evaluate the echocardiographic diagnosis for ventricular non compaction cardiomyopathy (NCCM) in foetus and to analyze the pathologic features of NCCM.? METHODS: A total of 9 patients with fetal NCCM were examined by prenatal echocardiography from 2004 to 2013, which was compared with postnatal echocardiography or autopsy to analyze the fetal characteristic of myocardial ultrastructure.? RESULTS: The results of echocardiography displayed an excessive muscle trabecular meshwork and muscle trabecular crypt, and the ventricular myocardium and non-compaction/compaction ratio was >=2.0. Among the 9 fetuses of NCCM, 6 fetuses were involved in left ventricle, 2 in both left and right ventricles and 1 in right ventricle. Two fetuses were confirmed by postnatal echocardiography, the remaining 7 patients were chosen to terminate their pregnancies, which were confirmed by autopsy later. Muscle biopsies revealed the abnormal myocardial mitochondria, sarcomeres and myocardial fibrosis.? CONCLUSION: It is feasible to accurately diagnose NCCM by prenatal echocardiography. Fetal NCCM most often involves the left ventricle, but it can involve the right ventricle or both, too. The myocardial ultrastructure of fetal NCCM possesses certain unique characteristics, such as the low maturation of the mitochondria, sarcomeres and myocardial fibers. PMID- 26267689 TI - [Relationship between the ischemic ST-T changes in ECG and the coronary artery diseases]. AB - OBJECTIVE: To analyze the relationship between the ischemic ST-T changes in electrocardiogram (ECG) and the coronary artery diseases based on the perspective of diagnostics.? METHODS: A total of 341 patients, who underwent coronary angiography in Department of Cardiology of Xiangya Hospital, Central South University from June 2013 to April 2014, were enrolled for this study. The internationally recognized diagnostic criteria for ischemic ST-T changes in ECG and the Judkins diagnostic criteria for coronary angiography were applied, respectively. The sensitivity and specificity of ECG were analyzed.? RESULTS: There were more ischemic ST-T changes in women than that in men (P<0.01). Ischemic changes in coronary angiography were not significantly different between male and female patients (P>0.05). For ischemic diagnostic tests by ECG ST-T, the total sensitivity and specificity was 83.6% and 54.4%, respectively. The sensitivity and specificity was 82.3% and 68.0% or 85.0% and 28.2% in the male or female group, respectively. ? CONCLUSION: Ischemic ST-T changes in ECG possess important value in the diagnosis of the coronary artery diseases. The sensitivity of ECG in the diagnosis of myocardial ischemia in women was higher than that in men, whereas the specificity of ECG in the diagnosis of myocardial ischemia in men was higher than that in women. PMID- 26267690 TI - [Analysis of pulmonary dysfunction of 1 953 coal miners ?in Hunan Province]. AB - OBJECTIVE: To explore the effect of dust exposure, type of work, age, length of service and duration of dust exposure on pulmonary function in coal miners by pulmonary function tests.? METHODS: A total of 1 953 coal miners, who received occupational healthy examination and pulmonary function tests during June, 2013 and August, 2014 in Hunan Prevention and Treatment Institute, were enrolled for this study.? RESULTS: A total of 1 302 miners (66.7%) displayed pulmonary dysfunction, including 1 139 with mild dysfunction (58.3%) and 163 with moderate or more serious dysfunction (8.3%). The risk factors for pulmonary dysfunction were age (OR=1.329, 95% CI: 1.196-1.620), dust exposure duration (OR=1.267, 95% CI: 1.136-1.413) and type of works (mining workers OR=1.156, 95% CI: 1.033-1.293; all P<0.05).? CONCLUSION: The incidence rate of pulmonary dysfunction in coal miners is relatively high in Hunan Province. Most of them are mild dysfunction. The incidence rate of pulmonary dysfunction in mining works is statistically higher than that in other work types. Older workers and long duration-exposed workers are more likely to have pulmonary dysfunction. PMID- 26267691 TI - Prognostic value of statin for cancer patients: ?A Meta-analysis. AB - OBJECTIVE: To systematically evaluate the effect of statins on prognosis for patients with cancers.? METHODS: Literature on PubMed, EMbase and Cochrane library was screened from the establishment of databases to March, 2015 to find relevant studies. Random-effects models were used to calculate the pooled hazard ratios (HR) and 95% confidence interval (CI) for the association between statin use and all-cause mortality and cancer-specific mortality.? RESULTS: A total of 25 studies covered 523 193 patients were identified and included in this Meta analysis. The pooled effect showed that statin application was associated with a reduction in all-cause mortality in cancer patients (HR, 0.82; 95% CI: 0.76 to 0.89). A significantly decreased mortality in prostate cancer was revealed in subgroup by cancer sites (HR, 0.66; 95% CI: 0.52 to 0.83). In addition, sensitivity analysis demonstrated a weakened association between statin application and all-cause mortality after excluding the studies with shorter follow-up duration (HR, 0.91; 95% CI: 0.75 to 1.10).? CONCLUSION: A beneficial effect of statin on all-cause mortality and cancer-specific mortality is presented in patients with cancer. However, further studies are needed to confirm the long term effect. PMID- 26267692 TI - [Meta-analysis of endoscopic axillary lymph node dissection versus conventional open excision for breast cancer]. AB - OBJECTIVE: To compare the surgical outcome and the clinical value between endoscopic axillary lymph node dissection and conventional open excision in the treatment of breast cancer. ? METHODS: A computer-based online search of Medline, PubMed, Embase, Ovid, Cochrane Library, Vip, Wanfang, CNKI and Chinese Biological Medicine Database was performed, and conference literatures were manually searched. Using the Cochrane Collaboration guidelines, all randomized controlled trials comparing endoscopic axillary lymph node dissection and conventional open excision were systematically reviewed. The Cochrane Collaboration's RevMan 5.0 software was used for data analysis. ? RESULTS: A total of 25 studies involving 3 028 patients were included. The results of Meta-analyses showed that there were no significant difference in the number of lymph nodes harvested and recurrence between endoscopic axillary lymph node dissection and conventional open excision (P>0.05). The operative time of endoscopic axillary lymph node dissection was longer than that of conventional open excision. However, it was superior to open excision in the rate of complication and intra-operative blood loss (P<0.05).? CONCLUSION: As a minimally invasive surgery technique to treat breast cancer, endoscopic axillary lymph node dissection might be a promising replacement for conventional axillary lymph node dissection. PMID- 26267694 TI - [Relationship between perioperative blood transfusion and post-operative hospital infection in patients with closed traumatic brain injury]. AB - OBJECTIVE: To explore the relationship between allogeneic transfusion and hospital infections in patients with closed traumatic brain injury in the perioperative period.? METHODS: The clinical data of 181 patients with open brain surgery suffering closed brain injury in Changsha Central Hospital from February, 2012 to December, 2013 were retrospectively collected. The patients were divided into a mild and moderate brain injury group (n=83) and a severe brain injury group (n=98) according to evaluation system of Glasgow coma scale (GCS). They were also divided into a autologous transfusion plus mild and moderate brain injury group (n=14), a autologous transfusion plus severe brain injury group (n=10); an allogeneic transfusion plus mild and moderate brain injury group (n=31), an allogeneic transfustion plus severe brain injury group (n=70); a non transfusion plus mild and moderate brain injury group (n=38) and a non transfusion plus severe brain injury group (n=18) according to the transfusion styles. The hospital infection of all the patients was examined.? RESULTS: The rate of hospital infection was significantly higher in the severe brain injury group than that in the mild and moderate brain injury group (P<0.05). The rate of post-operative hospital infection in the allogeneic transfusion plus severe brain injury group was also significantly higher than that in the autologous transfusion plus severe brain injury group (P<0.05). Similarly, the rate of post operative hospital infection in the allogeneic transfusion plus mild and moderate brain injury group is higher than that in the non-transfusion plus mild and moderate brain injury group (P<0.05).? CONCLUSION: The allogeneic transfusion at perioperative period may be one of the risk factors for post-operative hospital infection in the closed brain injury patients. The more severe the injury is, the higher risk the hospital infection will be. PMID- 26267693 TI - [Heparin-induced thrombocytopenia in patients ?undergoing cardiac surgery]. AB - OBJECTIVE: To investigate the incidence for heparin-induced thrombocytopenia (HIT) in patients undergoing cardiac surgery and to evaluate the risk factors for the generation of HIT-antibody.? METHODS: A total of 315 patients undergoing cardiac surgery in the Department of Cardiothoracic Surgery, Xiangya Hospital between December, 2013 and July, 2014 were enrolled for this study. Among them, 120, 154 and 41 were for surgery of congenital heart defect, valve and coronary artery bypass graft, respectively. There were 170 male patients and 69 patients were under 18 years old. Platelet counts, HIT-antibody and concentration of platelet factor 4 (PF4) were tested before and after the surgery. Diagnosis of HIT was based on "4Ts" (Pretest Clinical Scoring System). ? RESULTS: HIT was diagnosed in 11 patients (3.5%, 11/315). And thromboembolic events occurred in 2 of 11 patients with HIT. The positive ratio for HIT-antibody was 36.5% (115/315). The coronary artery disease patients had a higher incidence of HIT than that of either the valve disease or the congenital heart defect (17.1%, 7/41 versus 1.9%, 3/154 or 0.8%, 1/120; P<0.05). The congenital heart defect patients had a higher positive ratio for HIT-antibody than that of both the valve disease and the coronary artery disease. The valve disease patients had a higher positive ratio for HIT-antibody than that of the coronary artery disease (51.7%, 62/120 versus 30.5%, 47/154 versus 14.6%, 6/41; P<0.05). Major postoperative complications occurred more frequently in HIT patients (36.4%, 4/11 versus 10.5%, 32/304; P<0.05). Age was a risk factor for HIT (P=0.030, OR=1.083, 95% CI 1.008-1.163). Cardiopulmonary bypass (CPB) (P=0.037, OR=3.113, 95% CI 1.071-9.050) and age (P<0.001, OR=0.970, 95% CI 0.959-0.982) were risk factors for HIT-antibody.? CONCLUSION: The incidence of HIT is low during cardiac surgery, but HIT is a highly risk factor for the major postoperative complications. More attentions should be paid to these severe complications and the risk factors for HIT. PMID- 26267695 TI - [Preliminary clinical observation for platelet-rich fibrin in site preservation]. AB - OBJECTIVE: To observe the clinical effect on site preservation with self platelet rich fibrin (PRF) in posterior dental areas after extraction.? METHODS: Thirty patients who asked to extract posterior teeth and were ready for dental implantation were enrolled. PRF was implanted immediately in alveolar fossa after extraction. Cone beam computer tomography (CBCT) images were taken after 4-6 months and the changes in height and width of alveolar bone were observed.? RESULTS: There was no statistical difference in the height and width between the alveolar bone treated with PRF after the extraction of tooth and the bone condition before the extraction of tooth.? CONCLUSION: The site preservative technology with PRF could maintain the mass of alveolar bone in posterior dental areas, which provide a better bone condition for later dental implantation. PMID- 26267696 TI - [WEE1, histone and tumor]. AB - WEE1 is an important factor for histone transcription, chromosome condensation and regulation of cell cycle progression. WEE1 kinase can phosphorylate Cdc2 and down-regulate Cdc2 kinase activity. It can regulate G2 to M phase transition and cell mitosis. It plays a key role in chromosome condensation delay and histone synthesis, suggesting the important functions of WEE1 in the occurrence and development in cancer. At present, a multiple WEE1 inhibitors have been discovered. A great progress has been made in combination of WEE1 inhibitors with DNA damage treatment (chemotherapy or radiotherapy), which makes WEE1 an important target in cancer treatment. PMID- 26267697 TI - [Advances in the relationship between leptin and hypertensive-left ventricular hypertrophy]. AB - Leptin is a protein hormone produced mainly by obese gene and secreted by adipose tissue and exerts the biological effects through leptin receptors. With the progress in research on the function and receptor signal transduction related leptin and leptin resistance, it has been found that leptin is associated with the development and progression of many cardiovascular diseases, such as hypertension and left ventricular hypertrophy. Some studies have reported that leptin resistance is the pathologic basis for a variety of cardiovascular diseases. This paper will briefly review the advances in the study of correlation between leptin and hypertensive-left ventricular hypertrophy (HLVH), focusing on the relationship between leptin and various factors related to HLVH, such as sympathetic nervous system, renin angiotensin aldosterone system, growth factors, inflammatory factors and insulin resistance. PMID- 26267698 TI - [Advances in clinical application of quantitative susceptibility mapping in central nervous system]. AB - Susceptibility weighted imaging (SWI) is a magnetic resonance technology with a high resolution, three-dimensional gradient echo and fully velocity compensated sequence. It is also sensitive to substance with different magnetisability. Based on the quantitative reconstruction of SWI, quantitative susceptibility mapping (QSM) has been used in monitoring the change of intravenous iron, calcium, microbleeds and oxygen content. This article summarizes principle of QSM and the latest progress of QSM application in the diseases of central nervous system. PMID- 26267699 TI - [Five-case report for transvenous epicardial pacemaker implantation via coronary sinus in patients after prosthetic tricuspid valve replacement]. AB - Five patients after prosthetic tricuspid valve, who received pacemaker implantation via coronary sinus during Oct, 2011 and Jul, 2014, were enrolled. Pacemakers were implanted via coronary vein in 5 patients without complications. The stimulation thresholds keep stable and symptoms (such as short breath and fatigue) were disappeared during the follow-up. For patients after tricuspid valve replacement, implantation of pacemaker via coronary sinus provides a safe and invasive approach and avoids opening the chest again. PMID- 26267700 TI - A frame-supported ultrathin electrospun polymer membrane for transplantation of retinal pigment epithelial cells. AB - We report on the design and fabrication of a frame-supported nanofibrous membrane for the transplantation of retinal pigment epithelial (RPE) cells, which is a promising therapeutic option for the treatment of degenerative retinal disorders. The membranous cell carrier prepared from 640 nm-thick poly(DL-lactide) fibres uniquely combines high porosity, large pore size and low thickness, to maximize the nutrient supply to the transplanted cells in the subretinal space and thus to enhance the therapeutic effect of the transplantation. The carrier was prepared by electrospinning, which made it easy to embed a 95 MUm-thick circular supporting frame 2 mm in diameter. Implantations into enucleated porcine eyes showed that the frame enabled the ultrathin membrane to be handled without irreversible folding, and allowed the membrane to regain its flat shape when inserted into the subretinal space. We further demonstrated that the minimum membrane thickness compatible with the surgical procedure and instrumentation employed here was as low as 4 MUm. Primary porcine RPE cells cultivated on the membranes formed a confluent monolayer, expressed RPE-specific differentiation markers and showed transepithelial resistance close to that of the native RPE. Most importantly, the majority of the RPE cells transplanted into the subretinal space remained viable. The ultrathin, highly porous, and surgically convenient cell carrier presented here has the potential to improve the integration and the functionality of transplanted RPE cells. PMID- 26267701 TI - Review on the effects of influenza vaccination during pregnancy on preterm births. AB - Pregnant women are considered to be susceptible to severe influenza illness and are recommended as a priority group to be targeted for influenza vaccination in countries with vaccination programs. Increased rates of poor birth outcomes have also been temporally associated with influenza infection, especially when pandemics strains emerge. Even though the primary purpose for influenza vaccination during pregnancy is to decrease the risk of influenza infection in the women, other potential benefits include protection of their young infants against influenza illness and possibly improving birth outcomes. The 2009 influenza A/H1N1 pandemic highlighted the importance of influenza vaccination during pregnancy, after pregnant women were identified as a group with heightened morbidity and mortality during the pandemic. A few studies conducted before the 2009/10 season and a large number of reports during and after the 2009 pandemic have assessed the association between maternal influenza vaccination and birth outcomes. Although these studies indicate that influenza vaccination is safe for both the mother and the fetus, there are conflicting data on the effect of vaccination in improving preterm birth rates. We reviewed the 2 published randomized control trials and other observational studies that explored the relationship between maternal influenza vaccination and preterm births. PMID- 26267702 TI - New and emerging models of human intelligence. AB - In the last decade, new models of human intelligence have altered the theoretical landscape in psychometrics and cognitive science. In the current article, we provide an overview of key distinguishing features of these new models. Compared to 20th century models of intelligence, the new models proposed in the 21st century are unique for three primary reasons; (1) new models interpret the general factor, or g, as an emergent property reflecting the pattern of positive correlations observed among test scores, not as a causal latent variable, and therefore challenge the notion of general ability, (2) new models bridge correlational and experimental psychology and account for inter-individual differences in behavior in terms of intra-individual psychological processes, and (3) new models make novel predictions about the neural correlates of intelligent behavior. PMID- 26267703 TI - The Effects of Ketogenic Diet on Seizures, Cognitive Functions, and Other Neurological Disorders in Classical Phenotype of Glucose Transporter 1 Deficiency Syndrome. AB - OBJECTIVES: The purpose of this study was to characterize patients who were diagnosed with glucose transporter protein 1 deficiency syndrome (Glut1D), and also to assess the efficacy of ketogenic diet (KD) therapy on seizure control, cognitive functions, and other neurological disorders. PATIENTS AND METHODS: We studied six unrelated patients with the classical phenotype of Glut1D, focusing on clinical and laboratory features, the KD therapy and outcome over the 25-month follow-up period. RESULTS: Five patients became seizure-free with the onset of ketosis, and anticonvulsants were discontinued. Other neurological features such as ataxia, spasticity, and dystonia showed a less striking improvement than seizure control. There was no significant change in the intelligence quotient (IQ) level or microcephaly. In all patients, alertness, concentration, motivation, and activity resulted in a moderate improvement of variable degree. The early-onset adverse effects of KD were observed in five patients. The KD regimen failed in one patient, therefore, his diet was changed with an alternative to KD. CONCLUSIONS: Treatment with KD resulted in a marked improvement in seizures and cognitive functions but its effect appeared to be less striking on the other neurological disorders of the patients. When the classic KD is not tolerated, an alternative to KD may be helpful. PMID- 26267704 TI - Idiopathic Acute Transverse Myelitis in Children: A Retrospective Series. AB - OBJECTIVE: Acute transverse myelitis (ATM) is a focal inflammatory disorder of the spinal cord, resulting in motor, sensory, and autonomic dysfunction. In this study, we delineate the clinical manifestations, neuroimaging characteristics, and outcome-associated risk factors in children with idiopathic ATM. METHODS: We retrospectively reviewed the medical charts and neuroimages in nine children aged younger than 18 years diagnosed with ATM between January 2006 and August 2014. RESULTS: The mean onset age was 5 years and 9 months. Infectious prodromes were observed in six patients. Leg weakness was observed in all patients, autonomic sphincter dysfunction was observed in seven patients, and sensory deficits on admission were observed only in four patients. The diagnosis was delayed in patients younger than 5.5 years compared with older children. The adverse outcomes cannot be predicted by the course of the disease, the laboratory findings, nor the extent of magnetic resonance imaging-detected spinal lesions; however, these outcomes can be predicted by poor early response to corticosteroids and the requirement of additional treatments (p < 0.05). CONCLUSION: The diagnosis of ATM is challenging in young children. Children with ATM who responded early to corticosteroids had more favorable outcomes than those who required additional therapies. PMID- 26267706 TI - In Silico Analysis for Five Major Cereal Crops Phytocystatins. AB - Five major cereal crops such as rice, wheat, maize, barley and sorghum are continuously threatened by a multitude of pathogens and other disorders. Cystatins offers a pivotal role in deciding the promising plant response. The use of bioinformatics tools for phylogenetic relationships of five major cereal crop (rice, wheat, maize, barley and sorghum) phytocystatins based on amino acid sequence information was elucidated, and their secondary and tertiary structures were investigated for structural comparisons. Twenty-eight distinct phytocystatins from 28 plant species were investigated. Phytocystatins could be divided into five distinct phylogenetic groups. Five major cereal crops their structural features were highly conserved, and their amino acid sequence similarities ranged from 48 to 86 %. A new highly conserved amino acid sequence motif, YEAKxWxKxF, in the C-terminal end being unique to phytocystatins was identified. The predicted 3D homology models showed a high conservation of the general central structure of the phytocystatins, i.e., the 4-5 anti-parallel [Formula: see text]-sheets, wrapping halfway round a single central [Formula: see text]-helix and particularly the three active site regions, the N-terminal, the first and second hairpin loops. Any structural differences seem to be mainly in the length of the N- and C-terminal, the length of the second hairpin loop and the fifth [Formula: see text]-sheet. Via docking experiments, small heterogeneities were observed in the vicinity of the OC-I active sites that seemed to be influential in the binding process and stability of the resultant inhibitor-protease complex. PMID- 26267707 TI - PGWD: Integrating Personal Genome for Warfarin Dosing. AB - Warfarin is a drug normally used in the prevention of thrombosis and the formation of blood clots. The dosage of warfarin is strongly affected by genetic variants of CYP2C9 and VKORC1 genes. Current technologies for detecting the variants of these genes are mainly based on real-time PCR. In recent years, due to the rapidly dropping cost of whole genome sequencing and genotyping, more and more people get their whole genome sequenced or genotyped. However, current software for warfarin dosing prediction is based on low-throughput genetic information from either real-time PCR or melting curve methods. There is no bioinformatics tool available that can take the high-throughput genome sequencing data as input and determine the accurate dosage of warfarin. Here, we present PGWD, a web tool that analyzes personal genome sequencing data and integrates with clinical information for warfarin dosing. PMID- 26267708 TI - QM/MM MD and Free Energy Simulation Study of Methyl Transfer Processes Catalyzed by PKMTs and PRMTs. AB - Methyl transfer processes catalyzed by protein lysine methyltransferases (PKMTs) and protein arginine methyltransferases (PRMTs) control important biological events including transcriptional regulation and cell signaling. One important property of these enzymes is that different PKMTs and PRMTs catalyze the formation of different methylated product (product specificity). These different methylation states lead to different biological outcomes. Here, we review the results of quantum mechanics/molecular mechanics molecular dynamics and free energy simulations that have been performed to study the reaction mechanism of PKMTs and PRMTs and the mechanism underlying the product specificity of the methyl transfer processes. PMID- 26267705 TI - Epigenetics and Primary Biliary Cirrhosis: a Comprehensive Review and Implications for Autoimmunity. AB - Primary biliary cirrhosis (PBC) is a chronic inflammatory autoimmune disease that develops based upon the interaction of genetic and environmental factors. Recent genome-wide association studies (GWAS) have identified dozens of predisposing variants including HLA, IL12A, and CTLA4 but have been disappointed in identifying a "smoking gun." These discoveries highlight the importance of the genetic background involved in immunological dysregulation. Although concordance rate of PBC in monozygotic (MZ) twins is among the highest reported in autoimmune disorders, incomplete disease concordance in twins associated with differentially expressed genes has been demonstrated. However, little is understood about how environmental aspects contribute to the disease and why middle-aged women are more susceptible. As a result, epigenetic factors, which convert signals indicating environmental changes into dynamic and heritable alterations of transcriptional potential, are getting increased attention by researchers in both basic and clinical studies. Among epigenetic mechanisms, the instability and skewed gene expression in the X chromosome may account for the female preponderance in PBC. In addition, transcriptional regulation of histone modification and DNA methylation underscores potential involvement in disease pathogenesis. High-throughput techniques are being used to identify epigenetic regulators. In this review, we attempt to outline recent progress regarding epigenetics in PBC and other autoimmune diseases. PMID- 26267709 TI - Textile dyes induce toxicity on zebrafish early life stages. AB - Textile manufacturing is one of the most polluting industrial sectors because of the release of potentially toxic compounds, such as synthetic dyes, into the environment. Depending on the class of the dyes, their loss in wastewaters can range from 2% to 50% of the original dye concentration. Consequently, uncontrolled use of such dyes can negatively affect human health and the ecological balance. The present study assessed the toxicity of the textile dyes Direct Black 38 (DB38), Reactive Blue 15 (RB15), Reactive Orange 16 (RO16), and Vat Green 3 (VG3) using zebrafish (Danio rerio) embryos for 144 h postfertilization (hpf). At the tested conditions, none of the dyes caused significant mortality. The highest RO16 dose significantly delayed or inhibited the ability of zebrafish embryos to hatch from the chorion after 96 hpf. From 120 hpf to 144 hpf, all the dyes impaired the gas bladder inflation of zebrafish larvae, DB38 also induced curved tail, and VG3 led to yolk sac edema in zebrafish larvae. Based on these data, DB38, RB15, RO16, and VG3 can induce malformations during embryonic and larval development of zebrafish. Therefore, it is essential to remove these compounds from wastewater or reduce their concentrations to safe levels before discharging textile industry effluents into the aquatic environment. PMID- 26267710 TI - Atmospheric-pressure chemical ionization tandem mass spectrometry (APGC/MS/MS) an alternative to high-resolution mass spectrometry (HRGC/HRMS) for the determination of dioxins. AB - The use of a new atmospheric-pressure chemical ionization source for gas chromatography (APGC) coupled with a tandem quadrupole mass spectrometry (MS/MS) system, as an alternative to high-resolution mass spectrometry (HRMS), for the determination of PCDDs/PCDFs is described. The potential of using atmospheric pressure chemical ionization (APCI) coupled to a tandem quadrupole analyzer has been validated for the identification and quantification of dioxins and furans in different complex matrices. The main advantage of using the APCI source is the soft ionization at atmospheric pressure, which results in very limited fragmentation. APCI mass spectra are dominated by the molecular ion cluster, in contrast with the high energy ionization process under electron ionization (EI). The use of the molecular ion as the precursor ion in MS/MS enhances selectivity and, consequently, sensitivity by increasing the signal-to-noise ratios (S/N). For standard solutions of 2,3,7,8-TCDD, injections of 10 fg in the splitless mode on 30- or 60-m-length, 0.25 mm inner diameter (id), and 25 MUm film thickness low polarity capillary columns (DB5MS type), signal-to-noise (S/N) ratios of >10:1 were routinely obtained. Linearity was achieved in the region (correlation coefficient of r(2) > 0.998) for calibration curves ranging from 100 fg/MUL to 1000 pg/MUL. The results from a wide variety of complex samples, including certified and standard reference materials and samples from several QA/QC studies, which were previously analyzed by EI HRGC/HRMS, were compared with the results from the APGC/MS/MS system. Results between instruments showed good agreement both in individual congeners and toxic equivalence factors (TEQs). The data show that the use of APGC in combination with MS/MS for the analysis of dioxins has the same potential, in terms of sensitivity and selectivity, as the traditional HRMS instrumentation used for this analysis. However, the APCI/MS/MS system, as a benchtop system, is much easier to use. PMID- 26267711 TI - Nonspecific transcription factor binding can reduce noise in the expression of downstream proteins. AB - Transcription factors (TFs) interact with a multitude of binding sites on DNA and partner proteins inside cells. We investigate how nonspecific binding/unbinding to such decoy binding sites affects the magnitude and time-scale of random fluctuations in TF copy numbers arising from stochastic gene expression. A stochastic model of TF gene expression, together with decoy site interactions is formulated. Distributions for the total (bound and unbound) and free (unbound) TF levels are derived by analytically solving the chemical master equation under physiologically relevant assumptions. Our results show that increasing the number of decoy binding sides considerably reduces stochasticity in free TF copy numbers. The TF autocorrelation function reveals that decoy sites can either enhance or shorten the time-scale of TF fluctuations depending on model parameters. To understand how noise in TF abundances propagates downstream, a TF target gene is included in the model. Intriguingly, we find that noise in the expression of the target gene decreases with increasing decoy sites for linear TF target protein dose-responses, even in regimes where decoy sites enhance TF autocorrelation times. Moreover, counterintuitive noise transmissions arise for nonlinear dose-responses. In summary, our study highlights the critical role of molecular sequestration by decoy binding sites in regulating the stochastic dynamics of TFs and target proteins at the single-cell level. PMID- 26267712 TI - Non-Band-Gap Photoexcitation of Hydroxylated TiO2. AB - The photochemistry of TiO2 has been studied intensively since it was discovered that TiO2 can act as a photocatalyst. Nevertheless, it has proven difficult to establish the detailed charge-transfer processes involved, partly because the excited states involved are difficult to study. Here we present evidence of the existence of hydroxyl-induced excited states in the conduction band region. Using two-photon photoemission, we show that stepwise photoexcitation from filled band gap states lying 0.8 eV below the Fermi level of rutile TiO2(110) excites hydroxyl-induced states 2.73 eV above the Fermi level that has an onset energy of ~3.1 eV. The onset is shifted to lower energy by the coadsorption of molecular water, which suggests a means of tuning the energy of the excited state. PMID- 26267713 TI - Treatment of Hypertrophic Osteoarthropathy With Underlying Pulmonary Adenocarcinoma Using Zoledronic Acid. PMID- 26267714 TI - Fibrodysplasia Ossificans Progressiva. PMID- 26267715 TI - Listeria Meningoencephalitis in a Patient With Rheumatoid Arthritis on Anti Interleukin 6 Receptor Antibody Tocilizumab. PMID- 26267716 TI - Dual-Energy Computed Tomography Demonstrating Destructive Calcium Pyrophosphate Deposition Disease of the Distal Radioulnar Joint Mimicking Tophaceous Gout. AB - Calcium pyrophosphate dihydrate deposition (CPPD) disease is a common etiology of crystalline arthropathy; however, it can manifest in multiple patterns such as acute calcium pyrophosphate (CPP) crystal arthritis, osteoarthritis with CPPD, and chronic CPP crystal inflammatory arthritis. Tumoral or tophaceous-like CPPD is a rare manifestation that is occasionally mistaken for gouty tophus or a soft tissue malignancy. Dual-energy computed tomography (DECT) is a new imaging modality currently utilized in assessing monosodium urate crystal deposition; however, its value in CPPD is uncertain. We describe a case using DECT to diagnose tumoral CPPD mimicking tophaceous gout versus recurrence of a previous synovial sarcoma. The imaging findings on DECT prevented unnecessary surgery to assess for possible malignancy, allowing for the prompt diagnosis of tumoral CPPD. Further studies should be performed to determine the role of DECT in assessing for crystalline deposition disease other than gout. PMID- 26267717 TI - Anti-Citrullinated Peptide Antibodies in Tophaceous Gout: Prevalence in a Polynesian Population. PMID- 26267718 TI - Intestinal Flora Modification of Arthritis Pattern in Spondyloarthropathy. AB - BACKGROUND: The reactive form of spondyloarthropathy appears inducible by exposure to agents of infectious diarrhea, but do those organisms represent the tip of the iceberg, as indicated by renewed interest in gastrointestinal flora? Prevalence of spondyloarthropathy (20% of chimpanzees [Pan] and 28% of gorillas) is independent of subspecies and species, respectively. However, there are major differences in arthritis patterns, a characteristic shared with humans. OBJECTIVES: Do patterns of arthritis correlate with gastrointestinal flora? Could such associated modifications be in the form of disease induction or represent protective effectors (at least against the extent of peripheral arthritis)? METHODS: The skeletons of 2 chimpanzee subspecies (79 Pan troglodytes troglodytes and 26 Pan troglodytes schweinfurthii) and 2 gorilla species (99 Gorilla gorilla and 38 Gorilla beringei) adults were examined, and arthritis pattern noted. Feces of Eastern (P. schweinfurthii and G. beringei) and Western (great apes collected in their normal ranges) apes were assessed for 16S rRNA c and its character. RESULTS: Patterns of arthritis recognized on examination of skeletons showed geographic variation in skeletal distribution. East African apes (P. troglodytes schweinfurthii and G. beringei) had pauciarticular arthritis and frequent sacroiliac disease, whereas West African apes (P. troglodytes troglodytes and G. gorilla) had polyarticular peripheral joint disease with minimal sacroiliac involvement. DNA evidence revealed that Corynebactericeae were prominently represented in great apes with polyarticular disease, whereas Dietzia and Bifidobacterium exposure correlated with reduced peripheral joint arthritis distribution. CONCLUSIONS: Suggestions of a protective effect (in this case, limiting extent of peripheral arthritis, but not the disease itself) offered by these organisms are well represented by documented effects in other diseases (eg, tuberculosis) in the zoologic record. Perhaps it is this disease-modifying character that reduces the extent of the peripheral erosive disease, while increasing propensity to axial (sacroiliac) disease. A potential role for probiotic organisms in management of arthritis in humans is suggested, as has been documented for tuberculosis, gastrointestinal disorders, and food allergies. PMID- 26267719 TI - Eculizumab Induces Sustained Remission in a Patient With Refractory Primary Catastrophic Antiphospholipid Syndrome. AB - Catastrophic antiphospholipid syndrome (CAPS) is fatal in approximately 44% of patients in whom the diagnosis is made, thus demonstrating the inadequacy of current medical therapy. In this report, we discuss a 47-year-old man with a known history of primary antiphospholipid syndrome, who presented with CAPS after undergoing cholecystectomy and a treatment-refractory early relapse after development of colitis. Given the potential therapeutic efficacy of complement inhibition in antiphospholipid syndrome, the patient was administered eculizumab, a terminal complement inhibitor. Progressive clinical improvement and laboratory improvement were observed upon initiation of eculizumab. He has remained in remission for over 16 months of follow-up while on eculizumab. In conclusion, this case represents successful use of eculizumab for the treatment of primary CAPS. PMID- 26267720 TI - New Frontiers in Psoriasis Treatment. PMID- 26267721 TI - Randomized Pilot Clinical Trial of Tofacitinib Solution for Plaque Psoriasis: Challenges of the Intra-Subject Study Design. AB - Intra-subject, left-right, randomized, controlled study designs are often used for proof-of-concept studies in dermatology. This design was used to evaluate the safety and efficacy of a topical solution of tofacitinib (NCT00678561), a small molecule Janus kinase inhibitor under investigation for the topical and oral treatment of patients with chronic plaque psoriasis. Eighty-one patients, each with matched left and right target plaques, were randomized to 2%, 0.2%, or 0.02% tofacitinib or vehicle solution once or twice daily. Patients treated one plaque as per their randomization group (2%, 0.2%, 0.02% tofacitinib, or vehicle solution), and used vehicle to treat the contralateral plaque for 4 weeks. Except during clinic visits, study drug applications were performed unsupervised outside the clinical trial site. Intra-subject, vehicle-adjusted mean percent change from baseline in Target Plaque Severity Score at week 4 (primary efficacy endpoint) was not significantly different from baseline for any treatment group (P values of 0.28-0.68). However, skin biopsy analyses detected tofacitinib in both tofacitinib- and vehicle-treated plaques of some patients, suggesting cross contamination or solution misapplication. Lack of efficacy with tofacitinib relative to vehicle may be due to the intra-subject study design with unsupervised applications. These findings have potential implications for future intra-subject studies of topical treatments. PMID- 26267722 TI - Emerging Oral Immunomodulators for the Treatment of Psoriasis: A Review of Phase III Clinical Trials for Apremilast and Tofacitinib. AB - BACKGROUND: Increased knowledge of the molecular regulatory mechanisms that contribute to the pathogenesis of psoriasis and other inflammatory diseases has created new opportunities for the development of targeted drug therapy for inflammatory conditions. Two new oral medications, apremilast and tofacitinib, have been developed for their immunomodulatory properties, and their potential efficacy in treating psoriasis is being evaluated. METHODS: We reviewed phase III randomized, placebo-controlled clinical trial results for apremilast and tofacitinib for efficacy and safety in psoriasis. RESULTS: Psoriasis Area and Severity Index (PASI) 75 after 16 weeks for apremilast was between 28.8% and 33.1%. PASI 75 was 39.5% after 12 weeks on tofacitinib 5 mg, and 63.6% after 12 weeks on tofacitinib 10 mg. Common side effects for both drugs included nasopharyngitis and upper respiratory tract infections. Gastrointestinal disturbance was common for apremilast. Dyslipidemia and infections were more common with tofacitinib than placebo. CONCLUSION: Both new oral medications, apremilast and tofacitinib, appear to be effective in treating psoriasis PMID- 26267723 TI - Reproducible Novel Transcriptional Differences Between Psoriatic Lesional and Non Lesional Skin Show Increased Inflammation and Metabolism. AB - BACKGROUND: Psoriasis is a common but complex chronic inflammatory skin Disease. Array-based studies can help identify therapeutic targets. OBJECTIVE: To reproducibly assess single-gene transcriptional changes in psoriatic skin. METHODS: We evaluated 210 top candidate genes from a first psoriasis study group (population 1), and then confirmed differential expression in a second independent psoriasis study group (population 2). RESULTS: One hundred and thirty eight differentially expressed genes were replicated in the 2 studies, of which 57 have not previously been reported as associated with psoriasis. This is significantly greater than the 10 expected false positives. Lesional skin vs uninvolved areas showed inflammatory and cell regulation changes. CONCLUSION: Previously undescribed psoriasis-associated genes revealed in this study may provide potential future targets for development and assessment of novel therapeutic agents for psoriasis. PMID- 26267724 TI - Essential Truths for the Care and Management of Moderate-to-Severe Psoriasis. AB - Psoriasis is a systemic inflammatory disease. Effective management requires treatment with agents targeting inflammation in skin, joints, and other tissues. Biologics for psoriasis are directed at more specific targets, have a better safety profile, are better tolerated, and are more effective than conventional systemic agents. Despite these advances, many patients with psoriasis remain undertreated, and overall patient satisfaction remains low. The dichotomy between ideal therapeutic outcomes and suboptimal outcomes (which are currently commonplace) is likely largely due to misperceptions about psoriasis and biologic treatments. This article discusses these misperceptions, including the notions that psoriasis is a benign disorder, and that conventional systemic therapies are safer than biologics and adequate for most patients with moderate-to-severe disease. We present practical and evidence-based discussions to refute these misconceptions and provide useful resources for providers and patients that support access to advanced therapies. We believe that biologics represent optimal treatment for most patients with moderate-to-severe psoriasis, and until more effective approaches are generated, these efficacious and target-specific approaches should become the standard of care. PMID- 26267725 TI - Effect of Field Treatment of Actinic Keratosis With Ingenol Mebutate Gel on the Identification of Lesions for Biopsy. AB - Actinic keratoses (AKs) are premalignant skin lesions caused by cumulative ultraviolet-light exposure that may progress to invasive squamous cell carcinoma (SCC). As the clinical presentation of AKs varies widely, only a histopathologic analysis of a biopsied sample can eliminate or confirm a diagnosis of invasive SCC. Reducing the burden of AK with a combination of lesion-directed and field directed treatments may help to identify persistent, suspicious lesions that require further evaluation. We present 10 cases of SCC that were identified and histologically confirmed in 7 patients after complete or substantial clearance of AKs by sequential treatment of sun-damaged skin with cryosurgery and ingenol mebutate. PMID- 26267727 TI - Desoximetasone 0.25% Spray for the Relief of Scaling in Adults With Plaque Psoriasis. AB - Data from two Phase 3, double-blind, randomized, vehicle-controlled parallel studies were evaluated to determine the efficacy and safety of twice daily desoximetasone 0.25% spray for the treatment of plaque psoriasis. In addition to global disease assessments, scaling assessments were performed at baseline and at weeks 1, 2, and 4. To qualify for inclusion, subjects were required to have a clinical diagnosis of stable plaque psoriasis involving >=10% of the body surface area (BSA), a combined target lesion severity score (TLSS) of >=7 for the target lesion, a plaque elevation score of >=3 (moderate) for the target lesion, and a Physician Global Assessment (PGA) score of 3 (moderate) or 4 (severe) at baseline for the overall disease severity. At the baseline visit, the mean proportions of BSA affected by psoriasis were 17% (range 10% to 86%) in the desoximetasone 0.25% spray group and 16% (range 10% to 70%) in the vehicle spray group. Approximately 90% of the patients in each group had moderate to very severe scaling at baseline. Desoximetasone 0.25% spray was effective with significant improvements in overall severity and was well tolerated, with dryness, irritation, and pruritus at the application site being the only reported adverse events occurring in >1% of patients, each of which occurred in less than 3% of patients. As a large proportion of psoriasis patients (94%) have reported being bothered by scaling, the relief of scaling was examined in these studies. At week 1, 69.7% of patients on desoximetasone 0.25% spray had scaling that was considered clear / almost clear / mild compared with 48.3% for those on vehicle spray ( P = .0027). By week 4, the proportion of patients with clear / almost clear / mild scaling had risen to 83.9% in the desoximetasone 0.25% spray group (P < .0001). After four weeks of treatment, 66.4% of patients in the topical corticosteroid group had an overall improvement of at least two grades of disease severity. This demonstrates that desoximetasone 0.25% spray provided fast and effective relief of scaling in patients with plaque psoriasis affecting 10% to 86% of their BSA. PMID- 26267726 TI - Secukinumab Improves Physical Function in Subjects With Plaque Psoriasis and Psoriatic Arthritis: Results from Two Randomized, Phase 3 Trials. AB - BACKGROUND: Interleukin (IL)-17A is a key cytokine in the pathogenesis of psoriatic disease of the skin and joints. In phase 3 trials, secukinumab, a fully human anti-IL-17A monoclonal antibody, demonstrated robust efficacy in psoriasis, with rapid onset, high response rates, and durable response. OBJECTIVE: To evaluate the efficacy of secukinumab in subjects with psoriasis and concomitant psoriatic arthritis (PsA) with respect to psoriasis symptoms and physical function, we conducted pre-specified subanalyses of the phase 3 FIXTURE and ERASURE trials. METHODS: The 52-week FIXTURE and ERASURE trials randomized subjects with moderate-to-severe plaque psoriasis to subcutaneous secukinumab 300 or 150 mg (Baseline, weeks 1, 2, 3, every 4 weeks from week 4 until week 48), etanercept 50 mg (twice weekly through week 12, once weekly thereafter through week 51; FIXTURE only), or placebo. In this analysis, changes in Health Assessment Questionnaire-Disability Index (HAQ-DI) and PASI 75 responses were assessed in subpopulations with concomitant PsA (n=196, FIXTURE; n=171, ERASURE). RESULTS: Physical functioning (mean change from Baseline in HAQ-DI) was greater with secukinumab 300 mg vs. placebo at week 12 in both trials (FIXTURE, -0.41 vs. 0.02/P=0.0001; ERASURE, -0.35 vs. -0.08/P=0.0003); corresponding values were 0.29 for etanercept and -0.19 for secukinumab 150 mg in FIXTURE and -0.18 for secukinumab 150 mg in ERASURE. Greater responses were seen in subjects with greater Baseline disability (HAQ-DI >=05). Week 12 PASI 75 responses were higher with secukinumab 300 mg/150 mg vs. placebo in FIXTURE (72%/59% vs. 2%) and ERASURE (68%/70% vs. 4%; all P<0.0001) and with secukinumab 300 mg vs. etanercept (72% vs 39%; P=0.0084). CONCLUSION: Secukinumab 300 mg produced significant improvement in psoriasis and physical functioning in subjects with concomitant PsA. ClinicalTrials.gov numbers: NCT01358578 (FIXTURE); NCT01365455 (ERASURE) PMID- 26267728 TI - Erythema of Rosacea: Validation of Patient's Self-Assessment Grading Scale. AB - BACKGROUND: Facial erythema is a primary feature of rosacea. Currently, no validated scales exist that can accurately capture a patient's self-assessment of their own facial erythema. During phase 2 studies for brimonidine tartrate gel, a 5-point numeric rating scale was developed as a tool to allow subjects to provide an independent assessment of visible changes to the facial erythema associated with their rosacea. OBJECTIVE: The objective of this study was to validate the revised patient's self-assessment (PSA) scale and evaluate it for statistical reliability and validity in quantification of facial erythema of rosacea. METHODS: The validity of the PSA scale was evaluated by assessing the test-retest reliability, construct validity, and known-groups validity based on the data collected during a Phase 2b study on brimonidine gel for the treatment of persistent facial erythema of rosacea. RESULTS: Based on the results of this evaluation, this PSA scale demonstrated test-retest reliability, construct validity, and known-groups validity. LIMITATIONS: Study results are most generalizable to those with moderate to severe erythema. CONCLUSION: The PSA is an appropriate scale to assess facial erythema associated with rosacea. PMID- 26267730 TI - The Presence of an Air Gap Between the Nail Plate and Nail Bed in Onychomycosis Patients: Treatment Implications for Topical Therapy. AB - BACKGROUND: Transungual nail penetrance has traditionally been considered to be the only route of delivery for topical antifungals in onychomycosis. Subungual penetrance may be an alternate route of delivery. OBJECTIVE: To evaluate the ability of efinaconazole vehicle solution to reach the site of toenail onychomycosis through application to the hyponychium or hyponychium and dorsal nail surface, and assess the impact of the air gap between the nail plate and nail bed. METHODS: Twenty-three participants with moderate to severe, mycologically-confirmed onychomycosis were enrolled (mean age, 48.5 years). Two separate applications of vehicle solution containing fluorescein for visualization were applied at the hyponychium or hyponychium and dorsal nail surface. Affected nails were later clipped to allow examination of the nail bed and further examination of the ventral surface of the nail. Spread of formulation was assessed under visible and UV light conditions by photographing target toenails after vehicle application and after nail clipping. RESULTS: There was a positive correlation between the size of the air gap and degree of affected nail involvement (R2=0.064). Assessments under both visible and UV light indicated that the vehicle had spread to the site of infection, with deposition of fluorescein wherever vehicle had reached, irrespective of application methodology or size of air gap. Nail clippings also indicated absorption into the ventral surface of the nail plate. LIMITATIONS: The relative contributions of subungual versus transungual application of drug to the nail plate to the efficacy of efinaconazole topical solution, 10% in treating onychomycosis were not assessed. CONCLUSIONS: This study suggests that the low surface tension vehicle developed for efinaconazole topical solution, 10% can reach the site of infection by application to the hyponychium, dorsal or ventral nail surface and nail folds. This multidirectional approach to drug delivery at the site of fungal infection may contribute to the magnitude of efficacy seen in clinical trials. PMID- 26267729 TI - Biologic and Conventional Systemic Therapies Show Similar Safety and Efficacy in Elderly and Adult Patients With Moderate to Severe Psoriasis. AB - BACKGROUND/OBJECTIVE: Despite the aging population, few studies have documented the treatment of geriatric psoriasis. The purpose of this study is to compare the efficacy, safety, and prescribing patterns of biologics and conventional systemic medications in elderly versus adult psoriasis. METHODS: All patient visits coded for psoriasis or psoriatic arthritis (ICD-9 696.1 or 696.0) at the Tufts Medical Center General Dermatology Clinic from January 1, 2008, to March 1, 2015 were included in this retrospective cohort study. The outcome measure used was the validated simple-measure for assessing psoriasis activity (S-MAPA), the product of the physician's global assessment and the body surface area. RESULTS: 194 patients who underwent 278 treatment courses were included in the study. 48 patients were included in the elderly cohort (>= 65 years old) and 146 in the adult cohort (18-64 years old). There was no significant difference in S-MAPA improvement at 12 weeks between the two cohorts when treated with biologics (42.92% improvement in adults, 48.77% in elderly; P=0.498) or conventional systemics (43.96% and 51.82%, respectively; P=0.448). Within the elderly cohort, there was no significant difference in efficacy of biologics versus conventional systemics at any time point. Topical prescription rates were significantly higher in the elderly cohort ( P=0.004) while biologic prescription rates were significantly lower ( P=0.014) despite the same baseline S-MAPA in both age groups. For both biologics and conventional systemics, there was no statistically significant intergroup difference in the rate of adverse events ( P=0.322 for biologics; P=0.581 for conventional systemics) or infection ( P=0.753 for biologics; P=0.828 for conventional systemics). Within the elderly cohort, there was a higher rate of adverse events with conventional systemic treatment than with biologic treatment ( P=0.033). CONCLUSIONS: This study provides preliminary evidence to suggest that biologic and conventional systemic therapies are similarly safe and effective in the elderly and non-elderly cohorts. Within the elderly population, biologics may be a safer option than conventional systemic agents. PMID- 26267731 TI - Efficacy of Adalimumab Compared With Methotrexate or Placebo Stratified by Baseline BMI in a Randomized Placebo-Controlled Trial in Patients With Psoriasis. AB - INTRODUCTION: In the Comparative Study of Humira vs Methotrexate vs Placebo In Psoriasis Patients (CHAMPION) study, significantly more patients achieved >=75% improvement in the Psoriasis Area and Severity Index (PASI75) and >=90% improvement (PASI90) after 16 weeks of treatment with adalimumab (80 mg at week 0, then 40 mg every other week starting at week 1) compared with methotrexate (up to 25 mg/week orally) or placebo. In this exploratory analysis, the efficacy of adalimumab was evaluated in a subset of the CHAMPION patient population stratified by baseline body mass index (BMI). METHODS: PASI responses and Dermatology Life Quality Index (DLQI) scores through 16 weeks of treatment were examined by baseline BMI category (<25 kg/m2 [normal], 25 to <30 kg/m2 [overweight], and >=30 kg/m2 [obese]) in patients with psoriasis with a baseline PASI total score >=12. Treatment differences between the adalimumab and the methotrexate or placebo groups were compared using Fisher's exact test for PASI responses and 1-way analysis of variance for DLQI scores. RESULTS: In all BMI categories, adalimumab treatment led to significantly greater rates of PASI75/90 responses at weeks 12 and 16 compared with methotrexate or placebo (P<0.05 for all). In normal weight, overweight, and obese patients at week 16, the respective PASI75 response rates were 85.0%, 85.7%, and 61.3% with adalimumab; 43.3%, 29.3%, and 26.1% with methotrexate; and 28.6%, 16.7%, and 0% with placebo. PASI90 response rates were 70.0%, 53.6%, and 35.5% with adalimumab; 26.7%, 7.3%, and 8.7% with methotrexate; and 9.5%, 16.7%, and 0% with placebo. Across all BMI subgroups, the greatest decreases in DLQI scores from baseline occurred in the adalimumab group. CONCLUSION: Significantly higher PASI75/90 response rates and more pronounced improvements in DLQI scores at week 16 were identified in patients treated with adalimumab, compared with methotrexate or placebo, regardless of baseline BMI category. PMID- 26267732 TI - Prognostic Factors for Complete Cure Following Treatment of Mild and Moderate Toenail Onychomycosis With Efinaconazole Topical Solution 10. AB - OBJECTIVE: To identify those patients who are more likely to achieve treatment success with efinaconazole topical solution 10% based on clinical improvement and mycological status during treatment. METHODS: A subgroup analysis of patients, aged 18 to 70 years, randomized to receive efinaconazole topical solution 10% or vehicle from 2 identical multicenter, double-blind, vehicle-controlled 48-week studies evaluating safety and efficacy. The primary end point, complete cure rate (0% clinical involvement of target toenail, and both negative potassium hydroxide examination and fungal culture) at week 52 was evaluated based on mycologic cure at week 24, and the degree of clinical improvement in nail involvement at week 12. RESULTS: Over a quarter (25.1%) of patients treated with efinaconazole topical solution 10% who could demonstrate at least 10% improvement in affected nail involvement by week 12 progressed to complete cures at week 52. Similarly, 21.7% of patients who demonstrated mycologic cure at week 24 achieved complete cures at week 52. CONCLUSIONS: Early clinical improvement and mycologic clearance may help to predict treatment success with efinaconazole topical solution 10%. PMID- 26267733 TI - Tumor Necrosis Factor-alpha Inhibitor Use in Psoriasis Patients With a First degree Relative With Multiple Sclerosis. AB - Tumor necrosis factor (TNF)-alpha inhibitors are currently the gold standard for treating moderate to severe plaque psoriasis and other immune-mediated diseases. The presence of previously existing demyelinating disease is amongst the contraindications to their use. However, controversy surrounds the use of TNF alpha inhibitors in patients who are more predisposed to developing multiple sclerosis (MS), specifically first-degree relatives of MS patients. In fact, the major guidelines committees' recommendations on this issue by the American Academy of Dermatology, the British Association of Dermatologists, and the European S3-Guidelines are not consistent. The data we present suggest that the number needed to treat is at least an order of magnitude smaller than the number needed to harm across all comparisons of anti-TNF-alpha agents and first-degree relative relationships. Based on these data, physicians could weigh the treatment options available and work closely with neurological colleagues when prescribing anti-TNF-alpha therapy in this patient population rather than practicing absolute prohibition of anti-TNF-alpha agents in patients who have a first-degree relative with MS. PMID- 26267734 TI - Systemic Treatment of Recalcitrant Pediatric Psoriasis: A Case Series and Literature Review. AB - BACKGROUND/PURPOSE: No systemic drugs are approved by the Food and Drug Administration to treat pediatric psoriasis due to a lack of supporting data. The purpose of this study is to present cases demonstrating the use of systemic drugs in pediatric psoriasis. METHODS: In this case series, data were collected on patients <= 18 years old with moderate-to-severe psoriasis treated with systemic medications (traditional systemic drugs or biologics) from 2008 through 2014. Efficacy was measured using the validated simple measure for assessing psoriasis activity (S-MAPA), and the product of the body surface area and Physician Global Assessment. RESULTS: Twenty-seven patients aged 5 to 18 years were eligible, and 56 treatment courses were analyzed. Methotrexate (MTX) was the most frequently prescribed systemic (70%), followed by etanercept (59%). Clearance rates were highest on biologic medications (67% for etanercept and adalimumab, 33% for ustekinumab). Phototherapy, cyclosporine, and MTX were less effective in clearing psoriasis, although they were successful in improving S-MAPA >= 50% from baseline 100%, 67%, and 36% of the time, respectively. The most common adverse events were sunburn for patients on narrowband ultraviolet B phototherapy (14%), gastrointestinal intolerance and minor infections for patients on MTX (16% each), and minor infections for patients on etanercept (25%) and adalimumab (33%). The most common reasons for discontinuation were secondary failure (38% for etanercept, 33% for adalimumab) or lack of response (37% for MTX, 33% for cyclosporine). CONCLUSION: Although phototherapy, MTX, and cyclosporine are effective for controlling resistant pediatric psoriasis, concerns about long-term safety or inconvenience have led people to consider biologics in their place. However, there is a lack of literature on the use of biologics in pediatric psoriasis. These cases attest to the safety and efficacy of etanercept, adalimumab, and ustekinumab in pediatric psoriasis, expanding the treatment repertoire and guiding dermatologists in better managing recalcitrant pediatric psoriasis. PMID- 26267735 TI - The Use of Methotrexate, Alone or in Combination With Other Therapies, for the Treatment of Palmoplantar Psoriasis. AB - Palmoplantar psoriasis is a chronic debilitating type of psoriasis. Treatment options for this disease are poorly studied. This chart review evaluated the use of methotrexate alone and in combination with 7 other systemic therapies in 48 patients with palmoplantar psoriasis. The findings demonstrate that methotrexate is a relatively well-tolerated and effective treatment for palmoplantar psoriasis, amenable as either monotherapy or in combination with other systemic agents. PMID- 26267736 TI - Tumor Necrosis Factor Inhibitor Primary Failure Predicts Decreased Ustekinumab Efficacy in Psoriasis Patients. AB - BACKGROUND: Additional studies are needed to examine the efficacy of ustekinumab in psoriasis patients who have previously been exposed to tumor necrosis factor inhibitors (TNFi). OBJECTIVE: To examine the predictive effect of TNFi primary failure and the number of TNFi exposures on the efficacy of ustekinumab in psoriasis treatment. METHODS: This retrospective study examined 44 psoriasis patients treated at the Tufts Medical Center Department of Dermatology between January 2008 and July 2014. Patients were selected if they were treated with ustekinumab and had >= 1 previous TNFi exposure. The following subgroups were compared: patients with vs without a previous TNFi primary failure, and patients with one vs multiple previous TNFi exposures. The efficacy measure used was the previously validated Simple Measure for Assessing Psoriasis Activity (S-MAPA), which is calculated by the product of the body surface area and physician global assessment. The primary outcome was the percentage improvement S-MAPA from course baseline at week 12 of ustekinumab treatment. Secondary outcomes were the psoriasis clearance, primary failure, and secondary failure rates with ustekinumab treatment. RESULTS: Patients with a previous TNFi primary failure had a significantly lower percentage improvement in S-MAPA score at week 12 of ustekinumab treatment compared with patients without TNFi primary failure (36.2% vs 61.1%, P=.027). Multivariate analysis demonstrated that this relationship was independent of patient demographics and medical comorbidities. Patients with multiple TNFi exposures had a non-statistically significant lower percentage S MAPA improvement at week 12 (40.5% vs 52.9%, P=.294) of ustekinumab treatment compared with patients with a single TNFi exposure. CONCLUSIONS: Among psoriasis patients previously exposed to TNFi, a history of a previous TNFi primary failure predicts a decreased response to ustekinumab independent of patient demographics and medical comorbidities. PMID- 26267737 TI - Pulmonary Cryptococcosis in the Setting of Tofacitinib Therapy for Psoriasis. AB - Tofacitinib is a novel drug that inhibits the JAK-STAT signaling pathway. It has been approved for the treatment of psoriatic arthritis and it is under investigation for the treatment of psoriasis and other inflammatory disorders. We report a case of pulmonary cryptococcosis in an otherwise immunocompetent patient taking tofacitinib for psoriasis. We hypothesized that tofacitinib contributed to this infection through inhibition of cytokines required for differentiation of T cells and suppression of macrophage activation. As dermatologists begin to use this drug they should be aware of the potential for cryptococcocal infection, because delay of diagnosis may increase the risk of a life-threatening outcome. PMID- 26267738 TI - Pemphigoid Gestationis: A Case Report and Review of Management. AB - BACKGROUND: Pemphigoid gestationis (PG) is a rare pruritic autoimmune dermatosis associated with several adverse fetal outcomes. An appropriate pharmacotherapy regimen reduces these risks while also providing symptomatic relief. CASE: A woman in her second trimester presented with an intensely pruritic vesiculobullous rash diagnosed as PG. She was started on prednisone and gradually tapered to an appropriate maintenance dose until her uncomplicated delivery of a full-term healthy newborn. CONCLUSION: Proper management of PG requires a suitable pharmacotherapy regimen, close observation, and collaboration with a multi-disciplinary treatment team. These steps are crucial to reduce maternal morbidity, lessen fetal risk, and adequately prepare for the possibility of unfavorable obstetric outcomes. PMID- 26267739 TI - Emotional Lability in Patients with Attention-Deficit/Hyperactivity Disorder: Impact of Pharmacotherapy. AB - Attention-deficit/hyperactivity disorder (ADHD) is a neurobehavioral disorder defined by persistent inattention and/or hyperactivity and impulsivity. These symptoms occur more frequently and are more severe in individuals with ADHD compared with those at a similar developmental level without ADHD, and can be conceptualized as deficits in executive functioning (EF). EF includes domains of metacognition and inhibition, which influence the ability to regulate responses elicited by emotional stimuli. EF deficits can lead to emotional lability (EL), which is characterized by sudden changes in emotion and behaviors of inappropriately high intensity that may include sudden bouts of anger, dysphoria, sadness, or euphoria. EL is common and estimated to occur in about 3.3-10% of the population. Recent estimates of EL prevalence in children and adolescents with ADHD range from 38 to 75%. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition does not include EL in diagnostic criteria for ADHD, but does include ADHD-associated features of low frustration tolerance, irritability, or mood lability. The neurobiological basis of EL is not well understood, but brain imaging studies support dividing EF into "cool" cognitive networks encompassing attention and planning activities, and "hot" motivational networks involved in temporal discounting, reward processing, and reward anticipation. Dysfunction in "hot" networks is thought to be related to EL. EL symptoms are associated with more severe ADHD and co-morbidities, have significant impact on functioning, and may respond to treatment with medications frequently used to treat ADHD. Treatment outcomes and areas for future research are discussed. PMID- 26267740 TI - Prediction of improvement in left atrial function index after catheter ablation for atrial fibrillation. AB - PURPOSE: Although left atrial function index is reportedly a possible predictor of hospitalization for heart failure and of stroke irrespective of the presence or not of atrial fibrillation (AF), the effects of catheter ablation on left atrial function index have not yet been reported. METHODS: We performed catheter ablation on 55 patients (age 56.6 +/- 9.6 years; 44 men; 30 with paroxysmal and 25 with persistent, long-standing AF) and evaluated them by transthoracic echocardiography preoperatively and 3 monthly for 12-24 months after catheter ablation. We then compared clinical characteristics and echocardiographic variables before catheter ablation between two groups: the 42 subjects with the most recent left atrial function index <30 and the 13 in which it was >=30. RESULTS: Left atrial function index improved after catheter ablation in both groups, plateauing 6 months after the procedure. Univariate analysis showed statistically significant differences in the prevalence of chronic AF and left atrial emptying fraction, diameter, and maximum and minimum volume (prevalence of chronic AF, p < 0.05; others, p < 0.01) between the groups. Multivariate analysis showed that only maximum left atrial volume predicts left atrial function index after catheter ablation (p < 0.05). In addition, we used ROC analysis to calculate a cutoff value for LA maximum volume as a good predictor and found that a good cutoff value was 63.5 mL, the sensitivity and specificity being 0.75 and 0.75, respectively. CONCLUSIONS: Catheter ablation improves left atrial function index. However, in patients with left atrial maximum volume of over 63.5 mL on echocardiography, the index did not recover to within the normal range after catheter ablation. PMID- 26267741 TI - Right ventricular failure after left ventricular assist devices. AB - Most patients with advanced systolic dysfunction who are assessed for a left ventricular assist device (LVAD) also have some degree of right ventricular (RV) dysfunction. Hence, RV failure (RVF) remains a common complication of LVAD placement. Severe RVF after LVAD implantation is associated with increased peri operative mortality and length of stay and can lead to coagulopathy, altered drug metabolism, worsening nutritional status, diuretic resistance, and poor quality of life. However, current medical and surgical treatment options for RVF are limited and often result in significant impairments in quality of life. There has been continuing interest in developing risk models for RVF before LVAD implantation. This report reviews the anatomy and physiology of the RV and how it changes in the setting of LVAD support. We will discuss proposed mechanisms and describe biochemical, echocardiographic, and hemodynamic predictors of RVF in LVAD patients. We will describe management strategies for reducing and managing RVF. Finally, we will discuss the increasingly recognized and difficult to manage entity of chronic RVF after LVAD placement and describe opportunities for future research. PMID- 26267742 TI - The failing heart is a major source of circulating FGF23 via oncostatin M receptor activation. PMID- 26267743 TI - Heart transplantation of Middle Eastern patients in the United States: A brief report from the UNOS database. PMID- 26267744 TI - Bacteremic Inquilinus limosus empyema in an Australian lung transplant patient with cystic fibrosis. PMID- 26267745 TI - Association of total serum antioxidant capacity with the Tei index in echocardiography in patients with microvascular angina. AB - OBJECTIVES: Cardiac syndrome X (CSX) is a condition characterized by exercise induced chest pain that occurs considering a normal coronary angiogram. We aimed to investigate the total serum antioxidant capacity (TAC) and biventricular global functions using echocardiography in patients with CSX. PATIENTS AND METHODS: The study population included 55 patients with typical anginal symptoms and a positive exercise stress test, or ischemia in myocardial perfusion scintigraphy and normal coronary arteries detected angiographically, and 49 healthy volunteers with atypical chest pain and a negative stress test. TAC was assessed from blood samples. Transthoracic echocardiography was performed for the entire study population. The Tei index was calculated using the formula IVCT+IVRT/ET. RESULTS: TAC was found to be significantly lower in the CSX group compared with the control group (0.70+/-0.37 vs. 1.5+/-0.30, respectively, P<0.001). The Tei index was significantly higher in patients with CSX than the control group (0.60+/-0.18 vs. 0.42+/-0.12, respectively, P<0.001).There was a significant and inverse relationship between TAC and the Tei index (r=-0.41, P<0.001). When we divided the study population according to the normal range of TAC into the decreased TAC group (<1.30 mmol/l), the normal TAC group (1.30-1.77 mmol/l), and the increased TAC group (>1.77 mmol/l), it was found that the Tei index was higher in the decreased TAC group compared with the other groups (0.66+/-0.18 vs. 0.49+/-0.10 and 0.46+/-0.13 mmol/l, P<0.001, respectively). CONCLUSION: Our study suggested that TAC was significantly decreased in CSX patients and decreased antioxidant levels were related to impaired Tei index in echocardiography in patients with microvascular angina. PMID- 26267746 TI - Epicardial adipose tissue thickness can be used to predict major adverse cardiac events. AB - OBJECTIVE: Increase in epicardial adipose tissue (EAT) thickness is associated with subclinical and manifest coronary artery disease. In addition, it is associated with the severity and extent of coronary atherosclerosis. We aimed to investigate whether increased EAT thickness is associated with adverse cardiovascular outcomes. PATIENTS AND METHODS: Two hundred consecutive patients who were admitted with stable angina pectoris, unstable angina pectoris or acute myocardial infarction (MI), and had undergone coronary angiography were included and followed for revascularization, nonfatal MI, hospitalization for heart failure and cardiovascular death for 26 (5-30) months. RESULTS: There were significantly more revascularizations, nonfatal MI and cardiovascular death in patients with an initial EAT thickness more than 7 mm (P<0.001 for all). Significant predictors of cardiovascular death were identified as an EAT thickness more than 7 mm [hazard ratio (HR) 1.9, 95% confidence interval (CI) 0.4 8.3, P=0.039] and diabetes (HR 3.42, 95% CI 0.7-17.5, P=0.014) in the multivariate Cox regression analysis. Event-free survival for cardiovascular death in the EAT up to 7 mm group was 97.9%, whereas it was 90.7% in the EAT more than 7 mm group (P=0.021). In addition, significant predictors of MI were identified as an EAT thickness more than 7 mm (HR 2.4, 95% CI 0.6-10.0, P=0.021) and diabetes (HR 3.4, 95% CI 1.0-11.2, P=0.04). Event-free survival for MI in the EAT up to 7 mm group was 96.4%, whereas it was 68.2% in the EAT more than 7 mm group (P=0.001). CONCLUSION: Increase in EAT thickness independently predicts adverse cardiac events including MI and cardiovascular death. PMID- 26267747 TI - Effects of liposomal prostaglandin E1 on periprocedural myocardial injury in patients with unstable angina undergoing an elective percutaneous coronary intervention. AB - OBJECTIVES: The aim of this study was to explore whether intravenous administration of liposomal prostaglandin E1 (lipo-PGE1) can reduce the incidence of periprocedural myocardial injury (PMI) in patients with unstable angina undergoing an elective percutaneous coronary intervention (PCI). PATIENTS AND METHODS: In this randomized-controlled study, a total of 219 patients were randomly assigned to a lipo-PGE1 group (n=110) and a control group (n=109). Patients in the lipo-PGE1 group received 20 MUg/day of lipo-PGE1 diluted in 10 ml of normal saline through an intravenous injection over 5 min starting at 3 days before PCI and continuing for 4 days after PCI. In the control group, 10 ml of normal saline was administered using the same method. The primary end point was the occurrence of PMI defined as an elevation of cardiac troponin I above the upper limit of normal within 24 h after the procedure. The secondary end points were (i) changes in inflammatory factors including plasma high-sensitivity C reactive protein, tumor necrosis factor alpha, and interleukin 6 before and at 24 h after PCI; (ii) the incidence of major adverse cardiac events in the patients during hospitalization and 30 days of follow-up after discharge, including cardiac deaths, severe heart failure, malignant arrhythmias, and target vessel revascularization. RESULTS: Within 24 h after PCI, the incidence of PMI was significantly lower in the lipo-PGE1 group compared with that in the control group (20 vs. 36.69%, P=0.009). Although the procedure induced a significant increase in high-sensitivity C-reactive protein, tumor necrosis factor alpha, and interleukin 6 levels, the values were significantly lower in the lipo-PGE1 group than those in the control group at 24 h after PCI (P<0.05). The proportion of thrombolysis in myocardial infarction grade 3 in the lipo-PGE1 group was higher than that in the control group (92.72 vs. 82.56%, P=0.037). There were no significant differences between the lipo-PGE1 group and the control group in the incidence of major adverse cardiac events during hospitalization and 30 days of follow-up (2.1 vs. 4%, P=0.72). Multivariate logistic analysis showed that lipo PGE1 was an independent protective factor against PMI (odds ratio 0.385, 95% confidence interval 0.195-0.760, P=0.006). CONCLUSION: Intravenous lipo-PGE1 can reduce the incidence of PMI following elective PCI in patients with unstable angina. The benefit of lipo-PGE1 may be associated with the effects of anti inflammation as well as improvement in coronary microvascular perfusion. PMID- 26267748 TI - Elevated serum fibrinogen levels and risk of contrast-induced acute kidney injury in patients undergoing a percutaneous coronary intervention for the treatment of acute coronary syndrome. AB - OBJECTIVES: Contrast-induced acute kidney injury (CI-AKI) is a common complication of diagnostic and therapeutic catheterizations, especially in the setting of acute coronary syndrome (ACS). Fibrinogen is a well-known cardiovascular risk factor. We evaluated whether serum fibrinogen level is associated independently with CI-AKI in patients with ACS who underwent a percutaneous coronary intervention (PCI). METHODS: Patients (n=710, aged 61 +/- 13, 69% men) were classified into two groups: CI-AKI and non-CI-AKI. CI-AKI was defined as an increase of at least 0.5 mg/dl or at least 25% in the serum creatinine level within 72 h following PCI. RESULTS: CI-AKI occurred in 75 (10.6%) patients. We found significantly higher serum fibrinogen levels in patients who developed CI-AKI than in those who did not (498 +/- 152 vs. 386 +/- 96 mg/dl, P<0.001). Multivariate logistic regression analysis showed that serum fibrinogen level (odds ratio 1.006, 95% confidence interval 1.003-1.009, P<0.001), age, glomerular filtration rate, female sex, and white blood cell count were correlated with the development of CI-AKI. CONCLUSION: Serum fibrinogen level is associated independently with a higher risk of CI-AKI in patients with ACS undergoing PCI. PMID- 26267749 TI - Coronary spasm revascularized with a bioresorbable vascular scaffold. PMID- 26267750 TI - Measurement of retinal wall-to-lumen ratio by adaptive optics retinal camera: a clinical research. AB - PURPOSE: To measure the wall-to-lumen ratio (WLR) and the cross-sectional area of the vascular wall (WCSA) of retinal arterioles by an Adaptive Optics (AO) retinal camera. METHODS: Forty-seven human subjects were examined and their medical history was explored. WLR and WCSA were measured on the basis of retinal arteriolar wall thickness (VW), lumen diameter (LD) and vessel diameter (VD) assessed by rtx1 Adaptive Optics retinal camera. WLR was calculated by the formula [Formula: see text]. Arterio-venous ratio (AVR) and microvascular abnormalities were attained by quantitative and qualitative assessment of fundus photographs. Influence of age, arterial hypertension, body mass index (BMI) and retinal microvascular abnormalities on the WLR was examined. An age-adjusted WLR was created to test influences on WLR independently of age. Considering WLR and WCSA, a distinction between eutrophic and hypertrophic retinal remodeling processes was possible. RESULTS: The intra-observer variability (IOV) was 6 % +/- 0.9 for arteriolar wall thickness and 2 % +/- 0.2 for arteriolar wall thickness plus vessel lumen. WLR depended significantly on the wall thickness (r = 0.715; p < 0.01) of retinal arterioles, but was independent of the total vessel diameter (r = 0.052; p = 0.728). WLR correlated significantly with age (r = 0.769; p < 0.01). Arterial hypertension and a higher BMI were significantly associated with an increased age-adjusted WLR. WLR correlated significantly with the stage of microvascular abnormalities. 55 % of the hypertensive subjects and 11 % of the normotensive subjects showed eutrophic remodeling, while hypertrophic remodeling was not detectable. WLR correlated inversely with AVR. AVR was independent of the arteriolar wall thickness, age and arterial hypertension. CONCLUSIONS: The technique of AO retinal imaging allows a direct measurement of the retinal vessel wall and lumen diameter with good intra-observer variability. Age, arterial hypertension and an elevated BMI level are significantly associated with an increased WLR. The wall-to-lumen ratio measured by AO can be used to detect structural retinal microvascular alterations in an early stage of remodeling processes. PMID- 26267751 TI - Age-dependency of ocular parameters: a cross sectional study of young and elderly healthy subjects. AB - PURPOSE: To investigate the effect of aging on ocular parameters, including intraocular pressure (IOP), measured with different tonometry methods in healthy young (HY) and healthy elderly (HE) subjects and to study the effect of corneal parameters on tonometry methods. METHODS: In this prospective, cross-sectional study, fifty eyes of 50 HY subjects (28 females, 22-31 years of age) and 43 eyes of 43 HE subjects (22 females, 64-79) were included. IOP was measured with four tonometry methods in a standardized order: ocular response analyser (ORA), dynamic contour tonometry (DCT), applanation resonance tonometry (ART) and Goldmann applanation tonometry (GAT). Other measurements included axial length (AL), central corneal thickness (CCT), corneal curvature (CC), anterior chamber volume (ACV), corneal hysteresis (CH) and corneal resistance factor (CRF). RESULTS: The mean IOP (HY/HE; mmHg +/- standard deviation (SD)) was 12.2 +/- 2.2/14.1 +/- 3.5 with GAT. IOP was significantly higher (difference +/- standard error) in HE compared to HY measured with an ORA (+3.1 mmHg +/- 0.6), GAT (+1.9 +/- 0.6) and DCT (+1.6 +/- 0.6). No significant difference was found in IOP measured with ART. CH and ACV were significantly lower in HE compared to HY. There was no difference between the groups in CCT, CC, AL or CRF. No tonometry method was dependant on CCT or CC. CONCLUSIONS: IOP measured with an ORA and via DCT and GAT was higher in HE compared to HY Swedish subjects, while IOP measured with ART did not differ between the groups. In these homogeneous groups, tonometry methods were independent of CCT and CC. PMID- 26267752 TI - Lamina cribrosa depth according to the level of axial length in normal and glaucomatous eyes. AB - PURPOSE: To compare the lamina cribrosa (LC) depth of the optic nerve head in normal and glaucomatous eyes over a wide range of axial length (AXL). METHODS: A total of 402 eyes, including 210 normal and 192 glaucomatous eyes, were imaged by spectral domain optical coherence tomography. Normal and glaucomatous eyes were each divided into three subgroups according to the level of AXL; long (> 26 mm), mid-level (23-26 mm), and short (< 23 mm). Visual field mean deviation (VF MD), LC thickness, and LC depth were compared between normal and glaucomatous eyes in each of the AXL subgroups. These parameters were also compared between normal and glaucomatous eyes in the three AXL subgroups. Factors associated with LC depth in each AXL subgroup were evaluated by univariate and multivariate regression analyses. RESULTS: A comparison of the three AXL subgroups in normal eyes showed that the LC was thinnest in the long AXL subgroup (short; 189.7 +/- 24.1 MUm, mid level; 179.9 +/- 34.3 MUm, long; 149.2 +/- 36.2 MUm, p < 0.001), but LC depth did not differ significantly in the three subgroups (short; 527.1 +/- 144.4 MUm, mid level; 578.2 +/- 163.5 MUm, long; 594.4 +/- 187.5 MUm, p = 0.144). In glaucomatous eyes, glaucoma severity assessed by VF MD did not differ significantly among the three AXL subgroups (short; -6.99 +/- 8.50 dB, mid-level; -6.40 +/- 7.64 dB, long; -4.61 +/- 5.22 dB, p = 0.168). However, LC depth was greater in the long than in the short AXL subgroup (679.5 +/- 192.7 MUm and 555.9 +/- 134.1 MUm, respectively, p = 0.004), although neither subgroup differed significantly in LC depth from the mid-level AXL subgroup (611.8 +/- 162.3 MUm, p = 0.385, p = 0.090). LC thickness was significantly different between normal and glaucomatous eyes (p < 0.001). LC depth was not different between normal and glaucomatous eyes in both short and mid-level AXL subgroups (p = 0.297, 0.222), but differed in the long AXL subgroup (p = 0.022). The presence of glaucoma was associated with greater LC depth only in the long AXL subgroup (p = 0.012). CONCLUSIONS: LC depth may vary according to the level of AXL in glaucomatous eyes with a similar level of glaucoma severity, with the greatest LC depth found in eyes with long AXL. Those findings suggest that glaucomatous optic disc cupping would manifest differently according to the level of AXL. PMID- 26267753 TI - Symmetry warrants rational cooperation by co-action in Social Dilemmas. AB - Is it rational for selfish individuals to cooperate? The conventional answer based on analysis of games such as the Prisoners Dilemma (PD) is that it is not, even though mutual cooperation results in a better outcome for all. This incompatibility between individual rationality and collective benefit lies at the heart of questions about the evolution of cooperation, as illustrated by PD and similar games. Here, we argue that this apparent incompatibility is due to an inconsistency in the standard Nash framework for analyzing non-cooperative games and propose a new paradigm, that of the co-action equilibrium. As in the Nash solution, agents know that others are just as rational as them and taking this into account lead them to realize that others will independently adopt the same strategy, in contrast to the idea of unilateral deviation central to Nash equilibrium thinking. Co-action equilibrium results in better collective outcomes for games representing social dilemmas, with relatively "nicer" strategies being chosen by rational selfish individuals. In particular, the dilemma of PD gets resolved within this framework, suggesting that cooperation can evolve in nature as the rational outcome even for selfish agents, without having to take recourse to additional mechanisms for promoting it. PMID- 26267754 TI - Subfunctionalization of arylalkylamine N-acetyltransferases in the sea bass Dicentrarchus labrax: two-ones for one two. AB - Melatonin is an important component of the vertebrates circadian system, synthetized from serotonin by the successive action of the arylalkylamine N acetyltransferase (Aanat: serotonin->N-acetylserotonin) and acetylserotonin-O methyltransferase (Asmt: N-acetylserotonin->melatonin). Aanat is responsible for the daily rhythm in melatonin production. Teleost fish are unique because they express two Aanat genes, aanat1 and aanat2, mainly expressed in the retina and pineal gland, respectively. In silico analysis indicated that the teleost specific whole-genome duplication generated Aanat1 duplicates (aanat1a and aanat1b); some fish express both of them, while others express either one of the isoforms. Here, we bring the first information on the structure, function, and distribution of Aanat1a and Aanat1b in a teleost, the sea bass Dicentrarchus labrax. Aanat1a and Aanat1b displayed a wide and distinct distribution in the nervous system and peripheral tissues, while Aanat2 appeared as a pineal enzyme. Co-expression of Aanats with asmt was found in the pineal gland and the three retinal nuclear layers. Enzyme kinetics indicated subtle differences in the affinity and catalytic efficiency of Aanat1a and Aanat1b for indolethylamines and phenylethylamines, respectively. Our data are consistent with the idea that Aanat2 is a pineal enzyme involved in melatonin production, while Aanat1 enzymes have a broader range of functions including melatonin synthesis in the retina, and catabolism of serotonin and dopamine in the retina and other tissues. The data are discussed in light of the recently uncovered roles of N-acetylserotonin and N-acetyldopamine as antioxidants, neuroprotectants, and modulators of cell proliferation and enzyme activities. PMID- 26267755 TI - Subcutaneous mycoses in coastal Karnataka in south India. AB - BACKGROUND: Subcutaneous mycoses are chronic, localized infections of the skin and subcutaneous tissue which occur following traumatic implantation of the etiological agent. The causative organisms are soil saprophytes of regional epidemiology with varying ability to adapt to the tissue environment and elicit disease. OBJECTIVES: This study was conducted to evaluate the various types of subcutaneous mycoses, including actinomycotic mycetomas, in south coastal Karnataka, India. METHODS: Between January 2005 and January 2013, a total of 25 patients were diagnosed with subcutaneous mycoses based on a detailed clinical history and presentation, histopathology, and culture of organisms. RESULTS: Chromoblastomycosis was the infection most commonly seen (n = 16 patients, 64%), followed by mycetoma (n = 4, 16%), sporotrichosis (n = 4, 16%), and rhinoentomophthoromycosis (n = 1, 4%). The extremities were the most common site of involvement, with the lower limb being most affected (64%). Males were more commonly afflicted (64%) than females (36%). Most patients were agricultural workers, although preceding trauma was noted in only three patients. The majority of patients responded well to therapy and were disease-free on follow-up. CONCLUSIONS: Subcutaneous mycoses are a rare group of disorders. Chromoblastomycosis is the most frequent subcutaneous fungal infection in south India. Morphologically, chromomoblastomycoses present as verrucous, ulcerative, nodular, or eczematous lesions. Clinical diagnosis is important as culture is often negative. The incidence of infection is higher among rubber tappers. It is important to clinically differentiate chromoblastomycosis from tuberculosis verrucosa cutis. Most of the subcutaneous mycoses respond well to treatment, with the exception of rhinoentomophthoromycosis, which is a rare form of deep mycosis with associated mutilation. Eumycetomas are not observed in this part of India. PMID- 26267756 TI - Do people use the shortest path? An empirical test of Wardrop's first principle. AB - Most recent route choice models, following either the random utility maximization or rule-based paradigm, require explicit enumeration of feasible routes. The quality of model estimation and prediction is sensitive to the appropriateness of the consideration set. However, few empirical studies of revealed route characteristics have been reported in the literature. This study evaluates the widely applied shortest path assumption by evaluating routes followed by residents of the Minneapolis-St. Paul metropolitan area. Accurate Global Positioning System (GPS) and Geographic Information System (GIS) data were employed to reveal routes people used over an eight to thirteen week period. Most people did not choose the shortest path. Using three weeks of that data, we find that current route choice set generation algorithms do not reveal the majority of paths that individuals took. Findings from this study may guide future efforts in building better route choice models. PMID- 26267757 TI - Single Turnover Reveals Oxygenated Intermediates in Toluene/o-Xylene Monooxygenase in the Presence of the Native Redox Partners. AB - Toluene/o-xylene monooxygenase (ToMO) is a non-heme diiron protein that activates O2 for subsequent arene oxidation. ToMO utilizes four protein components, a catalytic hydroxylase, a regulatory protein, a Rieske protein, and a reductase. O2 activation and substrate hydroxylation in the presence of all four protein components is examined. These studies demonstrate the importance of native reductants by revealing reactivity unobserved when dithionite and mediators are used as the reductant. This reactivity is compared with that of other O2 activating diiron enzymes. PMID- 26267758 TI - Synergistic Effects of Binary-Solvent Annealing for Efficient Polymer-Fullerene Bulk Heterojunction Solar Cells. AB - Conjugated polymer-fullerene-based bulk-heterojunction (BHJ) organic solar cells (OSCs) have attracted tremendous attention over the past two decades because of their potential to develop low-cost and easy methods to produce energy from light. The complicated microstructure and morphology with randomly organized architecture of these polymer-fullerene-based active layers (ALs) is a key factor that limits photovoltaic performance. In this study, a binary-solvent annealing (BSA) approach was established to improve the poly(3-hexylthiophene):indene-C60 bisadduct-based AL for efficient BHJ-type OSCs by varying the second solvents with different boiling points (BP). Thus, we were able to change the evaporation behavior of cosolvents and consequently obtain the various microstructural properties of the AL. An in-depth study was conducted on the solvent-evaporation driven morphology of the active layer under various cosolvent conditions and its effect on the photovoltaic parameters of OSCs. Under the BSA processes, we found that the specimens with low-BP second solvents allows us to observe a more ideal AL for increasing photon absorption and efficient charge transport and collection at the respective electrodes, resulting in enhanced PCE of the corresponding OSCs. By contrast, the specimens with high-BP second solvents exhibit random microstructures, which are detrimental to charge transport and collection and lead to diminished PCE of the corresponding OSCs. By appropriately selecting the composition of a binary solvent, BSA can be employed as an easy method for the effective manipulation of the microstructures of ALs. BSA is a promising technique for the performance enhancement of not only OSCs but also other organic/polymeric-based electronic devices. PMID- 26267759 TI - Electronic Excited States of Tungsten(0) Arylisocyanides. AB - W(CNAryl)6 complexes containing 2,6-diisopropylphenyl isocyanide (CNdipp) are powerful photoreductants with strongly emissive long-lived excited states. These properties are enhanced upon appending another aryl ring, e.g., W(CNdippPh(OMe2))6; CNdippPh(OMe2) = 4-(3,5-dimethoxyphenyl)-2,6 diisopropylphenylisocyanide (Sattler et al. J. Am. Chem. Soc. 2015, 137, 1198 1205). Electronic transitions and low-lying excited states of these complexes were investigated by time-dependent density functional theory (TDDFT); the lowest triplet state was characterized by time-resolved infrared spectroscopy (TRIR) supported by density functional theory (DFT). The intense absorption band of W(CNdipp)6 at 460 nm and that of W(CNdippPh(OMe2))6 at 500 nm originate from transitions of mixed pipi*(C=N-C)/MLCT(W -> Aryl) character, whereby W is depopulated by ca. 0.4 e(-) and the electron-density changes are predominantly localized along two equatorial molecular axes. The red shift and intensity rise on going from W(CNdipp)6 to W(CNdippPh(OMe2))6 are attributable to more extensive delocalization of the MLCT component. The complexes also exhibit absorptions in the 300-320 nm region, owing to W -> C=N MLCT transitions. Electronic absorptions in the spectrum of W(CNXy)6 (Xy = 2,6-dimethylphenyl), a complex with orthogonal aryl orientation, have similar characteristics, although shifted to higher energies. The relaxed lowest W(CNAryl)6 triplet state combines pipi* excitation of a trans pair of C=N-C moieties with MLCT (0.21 e(-)) and ligand-to-ligand charge transfer (LLCT, 0.24-0.27 e(-)) from the other four CNAryl ligands to the axial aryl and, less, to C=N groups; the spin density is localized along a single Aryl-N=C-W-C=N-Aryl axis. Delocalization of excited electron density on outer aryl rings in W(CNdippPh(OMe2))6 likely promotes photoinduced electron-transfer reactions to acceptor molecules. TRIR spectra show an intense broad bleach due to nu(C=N), a prominent transient upshifted by 60-65 cm(-1), and a weak down-shifted feature due to antisymmetric C=N stretch along the axis of high spin density. The TRIR spectral pattern remains unchanged on the femtosecond-nanosecond time scale, indicating that intersystem crossing and electron-density localization are ultrafast (<100 fs). PMID- 26267760 TI - Linearly distributed indurated plaques on the left arm of an 8-year-old girl. PMID- 26267761 TI - In reference to A new theory on the pathogenesis of acquired cholesteatoma: Mucosal traction. PMID- 26267762 TI - Considering the Role of Physical Therapists Within the Treatment and Rehabilitation of Individuals With Eating Disorders: An International Survey of Expert Clinicians. AB - PURPOSE: Recent research has demonstrated that physical therapy may benefit the physical and mental health of people with eating disorders (EDs). Because this is a new and developing field, this study aimed to investigate the experience, practices and knowledge of international physical therapy experts to inform clinical practice, education and research. METHODS: An international cross sectional survey design was undertaken with experienced physical therapists within the field of EDs. Physical therapist responses were analysed with descriptive statistics and thematic analysis as appropriate. RESULTS: Twenty eight international physical therapists participated. On average, participants had 6.9 years (95% confidence interval: 3.1-10.7, n = 27) of clinical experience working in ED settings and devoted approximately 39.3% (95% confidence interval: 23.8-54.8, n = 27) of their time to treating individuals with EDs. Participants reported that physical therapy interventions have a diverse range of benefits on the physical, mental and disease-specific factors (e.g. binges) in people with EDs. The key role of physical therapists includes improving body awareness, especially during physical activity combined with psycho-education about healthy doses of physical activity. Physical therapists were able to identify a range of barriers and facilitators to physical activity in people with EDs. DISCUSSION: This paper provides a first step towards understanding the role and value of physical therapists working with individuals with EDs. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26267764 TI - What Surgeons Can Learn From the Emerging Science of Implementation. PMID- 26267763 TI - Evolutionary origin of Tbr2-expressing precursor cells and the subventricular zone in the developing cortex. AB - The subventricular zone (SVZ) is greatly expanded in primates with gyrencephalic cortices and is thought to be absent from vertebrates with three-layered, lissencephalic cortices, such as the turtle. Recent work in rodents has shown that Tbr2-expressing neural precursor cells in the SVZ produce excitatory neurons for each cortical layer in the neocortex. Many excitatory neurons are generated through a two-step process in which Pax6-expressing radial glial cells divide in the VZ to produce Tbr2-expressing intermediate progenitor cells, which divide in the SVZ to produce cortical neurons. We investigated the evolutionary origin of SVZ neural precursor cells in the prenatal cerebral cortex by testing for the presence and distribution of Tbr2-expressing cells in the prenatal cortex of reptilian and avian species. We found that mitotic Tbr2(+) cells are present in the prenatal cortex of lizard, turtle, chicken, and dove. Furthermore, Tbr2(+) cells are organized into a distinct SVZ in the dorsal ventricular ridge (DVR) of turtle forebrain and in the cortices of chicken and dove. Our results are consistent with the concept that Tbr2(+) neural precursor cells were present in the common ancestor of mammals and reptiles. Our data also suggest that the organizing principle guiding the assembly of Tbr2(+) cells into an anatomically distinct SVZ, both developmentally and evolutionarily, may be shared across vertebrates. Finally, our results indicate that Tbr2 expression can be used to test for the presence of a distinct SVZ and to define the boundaries of the SVZ in developing cortices. PMID- 26267766 TI - [Presentation]. PMID- 26267765 TI - High-content, full genome siRNA screen for regulators of oncogenic HRAS-driven macropinocytosis. AB - Uptake of nutrients, such as glucose and amino acids, is critical to support cell growth and is typically mediated by cell surface transporters. An alternative mechanism for the bulk uptake of nutrients from the extracellular space is macropinocytosis, a nonclathrin, and nonreceptor-mediated endocytic process, in which extracellular fluid is taken up into large intracellular vesicles called macropinosomes. Oncogenic transformation leads to the increased metabolic activity of tumor cells, and in the Ras-driven tumor part of this enhanced activity is the stimulation of macropinocytosis. To measure oncogene-dependent macropinocytosis, we used HeLa cells expressing oncogenic HRAS(G12D) driven from a Tet-regulated promoter. Upon oncogenic HRAS expression, the cells undergo metabolic changes that include the elevation of macropinocytosis. We detected macropinocytosis through the uptake of lysine-fixable tetramethyl rhodamine (TMR) Dextran (70 kDa) from the cell media into nascent intracellular macropinosomes. These macropinosomes were quantified by image-based high-content analysis, with the size, intensity, and position of macropinosomes measured. Using this model system, we ran a full genome-wide siRNA screen (siGenomeTM; GE) to identify genes involved in controlling oncogenic HRAS-dependent macropinocytosis. Hits from the primary screen were confirmed with siRNA reagents from a different library (GE, OTP), which allowed us to mitigate potential off-target effects. Candidate genes from this screen include known regulators of macropinocytosis as well as novel targets. PMID- 26267767 TI - [Nutritional problems of female adolescents]. AB - Feeding in infancy is necessary to allow proper growth and development. Health of these early stages of life may influence the development of many diseases in the future (atherosclerosis, osteoporosis, hypertension, obesity ...). Furthermore habits set in childhood will endure throughout life. Therefore, getting adequate dietary and health patterns in childhood is vital. In adolescence occur a number of changes: rapid growth, development of secondary sexual characteristics, changes in body composition, ... that will be a challenge when getting or keeping that adequate feeding and habits. In female population requirements of different micronutrients are increased (mainly iron) and also higher energy requirement than in later stages of life occurs. However, adolescents are the main population at risk for developing eating disorders, which can pose serious problems to meet these nutritional requirements to achieve optimal development. These features and others, such as pregnant adolescents, are what make them a population that should be taken special care from nutritional point of view. PMID- 26267768 TI - [Intake of vitamins D and K, and their impact on health in female population]. AB - INTRODUCTION: Vitamins D and K are essential for maintaining bone and its deficiency has been associated with several chronic diseases. OBJECTIVES: To know the intake of vitamins D and K in female population and analyze their involvement on health. METHODS: Literature research regarding the topic. RESULTS: Intake of vitamin D in the Spanish female population from 17 to 60 years is lower than the estimated average requirement in the 95.5% of the studied participants and 30.2% of the Spanish population does not meet the established adequate intake for vitamin K. Several studies have emphasized the importance of maintaining optimal nutrition status of vitamin D for its role in the maintenance of bone, but also for its involvement in body weight control and prevention of diseases (cardiovascular disease, type 2 diabetes, cancer). Vitamin K deficiency is also associated with decreased bone density and increased cardiovascular risk besides exerting a protective effect against type 2 diabetes. CONCLUSIONS: In female population, the intake of vitamin K, but especially vitamin D, is often lower than recommended. Since a worse nutritional status in these vitamins is associated with damage in bone health, weight control, as well as an increased risk of several diseases, it seems appropriate to monitor and improve their intake. PMID- 26267769 TI - [Nutritional problems in Spanish women; Results from the ANIBES Study]. AB - INTRODUCTION: Women have proved vulnerable with regard to their nutritional status at all stages of life and in a variety of physiological situations. In response to the need for more up-to-date and accurate information about the determinants of nutritional status and the quantification of diet specifically, the ANIBES (Anthropometry, Intake and Energy Balance in Spain) study was carried out among a representative group of Spaniards aged 9 to 75. OBJECTIVE: To describe and evaluate some of the results available on energy intake and food sources from the ANIBES Study related to Spanish women. METHODS: Using a representative sample (n = 2009, 996 women/1013 men) of the Spanish population (9 75 years old), the following studies were conducted: anthropometry, diet (using new technology--tablet computers), physical activity (using accelerometry and a validated questionnaire), and perceptions regarding different aspects related to food, nutrition, physical activity and energy balance. RESULTS: Energy intake was 1660 +/- 426.7 kcal/d, significantly lower than among males. When analysed by age group, only girls (9-12 years old) and adolescents (13-17 years old) meet the recent recommendations established by the European Food Safety Authority (EFSA). In particular, the average energy intake among older women (65-75 years old), 1476 +/- 359.9 kcal/d, is problematic with regard to adequate nutritional density. The caloric profile is unbalanced (17% E from protein; 41.2% from carbohydrates; 38.7% from lipids) for all age groups. The main source of energy comes from grains and their derivatives (27%), meat products and their derivatives (14.1%), oils and fats (13.1%) and milk and its derivatives (12.4%). DISCUSSION: The results are presented in tables and charts in accordance with their potential repercussions for the nutritional quality of the Spanish female diet to day, and compared with other Spanish and European studies. PMID- 26267770 TI - [Physical and sedentary activity as modulating factors of the nutritional status]. AB - Sedentary behavior and physical exercise seem to influence the nutritional status of the population independently. In this sense, sedentary behavior is associated inversely with healthy eating patterns and directly with BMI, body fat, risk of chronic diseases and psychological problems. By contrast, regular exercise is associated with a healthier diet and health benefits as the prevention or reduction of excess weight and disease prevention. However, it seems difficult to completely compensate, sedentary behavior and risk factors for health, with physical activity. To improve the nutritional status and health of the population would be advisable to increase non-sedentary behaviors and decrease the time spent in front of the screen. Also, it is encouraged to exercise regularly. PMID- 26267771 TI - [Wholegrain cereals and sanitary benefits]. AB - OBJECTIVES: Dietary guidelines indicate that to get a proper nutrition is recommended eating 3 or more servings per day of whole grain. However, the recommendation is little known in the Spanish population, and almost the entire population doesn't fulfill it. Therefore, the aim of this review is to analyze the nutritional and health benefits associated with the consumption of whole grain cereals and the potential benefits related to the meeting of this guideline. METHODS: Literature search regarding the topic. RESULTS: Whole grain cereals are rich in carbohydrates, fiber, vitamins and minerals, and its contribution to the average diet helps to achieve current recommended intakes and nutritional goals, so its consumption in the recommended amount supposes a nutritional benefit. Moreover, several studies indicate that increased consumption of whole grain cereal is associated with protection against various chronic degenerative diseases (cardiovascular, diabetes, cancer and metabolic syndrome), assisting in the maintenance of digestive health and body weight. These results may be due to the contribution of nutrients, fiber and phytochemicals of these foods, as well as the displacement of the diet of other products with a less desirable nutritional profile, taking into account the composition of the average Spanish diet. In fact, the consumption of whole grain cereals has been linked with a possible improvement in the intestinal microbiota and antioxidant protection. In spite of these advantages, cereal consumption is looked with suspicion by many individuals, especially those concerned about weight control and additional benefits associated to consumption of whole grain cereals are not known. CONCLUSIONS: Whole grain cereals should be daily consumed in amounts of 3 or more servings/day, to achieve the nutritional and health benefits described in numerous investigations. More outreach is needed to ensure that the guideline is known and it's applied. PMID- 26267773 TI - Role of eggs consumption in women at different life stages. AB - Although women need less energy than men, their recommended dietary intakes for some nutrients are similar or even higher. Some physiological situations can highlight those differences, such as growth, pregnancy, lactation and menopause. Nutritional deficiencies may impact on growth, fertility, pregnancy and newborn health, so in this context eggs are a food of great interest because of its essential and highly bioavailable nutrients, while providing few calories. In addition, and bearing in mind that life expectancy for women is generally higher than that of men, the likelihood of suffering chronic diseases and for a longer time is high. In this sense, eggs are very nutritive food, inexpensive and easy to prepare, easy to chew and digest, and are especially suitable for women in old age or more fragile situations. Nutrients and bioactive substances provided by eggs can help prevent chronic diseases and improve the health of women in the last stages of their life. PMID- 26267772 TI - [Benefits of moderate beer consumption at different stages of life of women]. AB - Beer is a natural beverage low calorie, low degree of alcohol, no fats or sugars and a significant amount of carbohydrates, vitamins, and proteins. Beneficial health qualities are based on the presence in the beer of antioxidant compounds (polyphenols), which reduce the presence of free radicals in the organism, and phytoestrogens, elements biosimilars to natural estrogens. In pregnant women, beer, obviously alcohol-free, presents elements in its composition that differ it from other fermented beverages as it is the folic acid, vitamin necessary to prevent defects of the neural tube in the fetus or regulate homocysteine. With regard to breastfeeding, beer alcohol-free supplementation increases the antioxidant activity in breast milk and therefore reduces the oxidative stress of the newborn after birth In menopause, the presence of antioxidants, vitamins, nutrients, and dietetic fiber, as well as phytoestrogens, is highly beneficial in the prevention of pathologies arising from the decline in estrogens. Osteoporosis also is effectively combated by the beer. The intake of beer, favors a greater bone mass in women, irrespective of their gonadal status. PMID- 26267774 TI - [Positive effects of wheat bran for digestive health; scientific evidence]. AB - Wheat bran (ST) is very rich in insoluble fiber, consisting mainly arabinoxylans and, to a lesser extent, cellulose and beta-glucans, as well as vitamins, minerals and antioxidants polyphenolic. The ST is involved in the regulation of gastrointestinal physiology and health: delayed gastric emptying and intestinal transit speeds and increases fecal bulk. The ST has an effect on faecal bulking greater than other grains such as oats or vegetables and fruits. However, phytic acid present in the bran may reduce the absorption of certain minerals (Ca, Mg, Fe and Zn), due to formation phytate-mineral complexes. Different studies have shown that consumption of bran has protective effect against different diseases: cardiovascular, obesity and some gastrointestinal diseases, including constipation, diverticular disease and colorectal cancer, among others. In Spain the consumption of fiber (18 g/day on average) is below the recommended (30 g/day), so the increased consumption of foods with wheat bran help achieve this recommendation and reduce the incidence of diseases associated a low intake of fiber. PMID- 26267775 TI - [Nutritional factors in preventing osteoporosis]. AB - Osteoporosis, main risk factor for suffering fragility fractures, is an important public health problem which has undoubted social, health and economic impact; but mainly causes pain, functional limitation and severe alterations in the patient's quality of life. Its current prevalence is very high and a further increase is expected due to a higher life expectancy and the progressive ageing of the population. In the prevention of osteoporosis, the main goal is to prevent fragility fractures; for this reason, it is necessary to: 1) promote bone formation in youth, to get sufficient bone mass peak, 2) reduce bone loss in adulthood, especially after menopause, 3) maintain bone health throughout life, and 4) prevent falls. There is enough evidence that multifactorial strategies (assessment of risk factors, healthy lifestyle habits, smoking cessation, moderation in alcohol consumption, physical exercise, outdoor activity with prudent exposure to sunlight, and a varied and balanced diet), are effective in the population at risk. Regarding factors for the prevention of osteoporosis, current recommendations are: increased consumption of calcium, phosphorus, magnesium and fluoride; provide adequate vitamin D (even with fortified food if necessary); consumption of foods rich in omega-3 acids; reduction of salt and prepared ready meals; sufficient but moderate intake of protein and, in the absence of intolerance, promote the consumption of milk and dairy products, especially yogurt and fermented milk products. PMID- 26267776 TI - [Microbiota in women; clinical applications of probiotics]. AB - The main function of vaginal microbiota is to protect the mucosa against the colonization and growth of pathogenic microorganisms. This microbiota is modified by hormonal activity. Its maximum concentration and effectiveness occurs during the fertile period, where there is a predominance of lactobacilli. When it is reduced (microbiota dysbiosis) leads to bacterial vaginosis and candida vaginitis which are common diseases in women. Consequently, instillation of lactobacilli in the vagina has beneficial effects on the symptomatology and prognosis of these illnesses. Breast milk is one of the key factors in the development of gut microbiota of the infant. There is an enteric-breast circulation, which is higher at the end of pregnancy and during breastfeeding. This circulation could explain the modulation of the breast microbiota by using probiotics. It could have a positive impact not only for the health of the mother, who would reduce the incidence of mastitis, but also for their infant. The use of probiotics is a hopeful alternative in various gynecological pathologies. However, it's is necessary first some well-designed, randomized trials with standardized methods and with a significant number of patients in order to confirm its benefits and allow us its use in protocols. PMID- 26267777 TI - [An overview of the beneficial effects of hydrolysed collagen intake on joint and bone health and on skin ageing]. AB - INTRODUCTION: Hydrolysate Collagen (HC) consists of small peptides with a molecular weight lower than 5.000 Da. produced from gelatinization and subsequent enzymatic hydrolysis of native collagen which is found in rich collagenic animal tissues. There is much evidence about the HC ingestion positive effect over degenerative joint and bones diseases. OBJECTIVE: The aim of this article is to review the present scientific studies about HC and to evaluate the HC ingestion therapeutical effects on some collagenic tissues as cartilage, bones and skin. RESULTS: Up to date, there are more than 60 scientific studies (in vitro, in vivo, clinics and on bioavailability) about HC ingestion efficacy on reducing collagen damage and loss consequences as joint pain and erosion (osteoarthritis), bone density loss (osteoporosis) and skin ageing. CONCLUSIONS: Preclinical studies show that HC stimulates collagenic tissue regeneration by increasing not only collagen synthesis but minor components (glycosaminoglycans and hyaluronic acid) synthesis as well. Clinical studies show that HC continual ingestion helps to reduce and prevent joint pain, bone density loss and skin ageing. These results as well as its high level of tolerance and safety make HC ingestion attractive for a long-term use in bone and joint degenerative diseases and in fight against skin ageing. PMID- 26267778 TI - [Nutrition and cancer]. AB - INTRODUCTION: It is known how diet plays an important role either in cancer occurrence or its prevention. METHODS: A complete revision on the literature has been performed trying to gain knowledge on the diets that can prevent for cancer occurrence, or those that can cause malignancies. RESULTS: Fruits and vegetables are the foods that can prevent from cancer disease, soya and fishes also have demonstrated as preventive from some types of malignancies. Clear factors causing cancer are red meat and processed meat, dairy products and alcohol. The protective roles of vitamins, antioxidants and micronutrients still have to be deeply investigated. Obesity is a clear risk factor for cancer, calorie reduction has been proposed as a factor that has protective properties in laboratory studies, but this has to be demonstrated in a clinical scenario. CONCLUSION: The diet surveillance and an adequate selection of foods can be a useful and cheap method for malignant disease prevention in the general population. PMID- 26267779 TI - Speciation and persistence of doxycycline in the aquatic environment: Characterization in terms of steady state kinetics. AB - The aim of the present work was to establish the kinetics for the degradation of doxycycline in the aquatic environment with a view to arriving at a kinetic model that can be used to predict the persistence of antibiotic with confidence. The degradation of doxycycline in both water and sediment phases of aquatic microcosm experiments, as well as in distilled water control experiments, was studied over a period of 90 days. An initial 21% loss due to adsorption by the sediment was observed in the microcosm experiment soon after charging. Biphasic zero-order linear rates of degradation, attributed to microbial degradation of the free and sediment or colloidal particle-adsorbed antibiotic, were observed for both water phase (2.3 * 10(-2) and 4.5 * 10(-3) MUgg(-1) day(-1)) and sediment phase (7.9 * 10(-3) and 1.5 * 10(-3) MUgg(-1) day(-1)) of the microcosm experiment. The covered distilled water control experiment exhibited a monophasic zero-order linear rate (1.9 * 10(-3) MUgg(-1) day(-1)) attributed to hydrolysis, while the distilled water experiment exposed to natural light exhibited biphasic liner rates attributed to a combination of hydrolysis and photolysis (2.9 * 10(-3) MUgg(-1) day(-1)) and to microbial degradation (9.8 * 10(-3) MUgg(-1) day(-1)). A kinetic model that takes into account hydrolysis, photolysis, microbial degradation as well as sorption/desorption by colloidal and sediment particles is presented to account for the observed zero-order kinetics. The implications of the observed kinetics on the persistence of doxycycline in the aquatic environment are discussed. PMID- 26267780 TI - Studies of biosorption of Pb2+, Cd2+ and Cu2+ from aqueous solutions using Adansonia digitata root powders. AB - The potentials of Adansonia digitata root powders (ADRP) for adsorption of Pb(2+), Cd(2+) and Cu(2+) from aqueous solutions was investigated. Physico chemical analysis of the adsorbent (ADRP) shows that hydroxyl, carbonyl and amino groups were predominant on the surface of the adsorbent. Scanning Electron Microscope (SEM) image revealed its high porosity and irregular pores in the adsorbent while the Energy Dispersive X-ray Spectrum showed the major element with 53.0% Nitrogen, 23.8% carbon, 9.1% calcium, 7.5% potassium and 6.6% magnesium present. The found optimal conditions were: initial concentration of the metal ions = 0.5 mg/L, pH = 5, contact time = 90 min, adsorbent dose = 0.4 g and particle size = 32 um. Freundlich isotherm showed good fit for the adsorption of Pb(2+), Cd(2+) and Cu(2+). Dubinin-Radushkevich isotherm revealed that the adsorption processes were physisorption Cd(II) and Cu(II) but chemisorption with respect to Pb(II) ions. The kinetics and thermodynamic studies showed that Pseudo second order and chemisorptions provided the best fit to the experimental data of Pb (II) ions only. Batch desorption result show that desorption in the acidic media for the metal ions were more rapid and over 90% of the metal ions were recovered from the biomass. PMID- 26267781 TI - Physical Absorption Of CO2 in Protic and Aprotic Ionic Liquids: An Interaction Perspective. AB - The physical absorption of CO2 by protic and aprotic ionic liquids such as 1 ethyl-3-methyl-imidazolium tetrafluoroborate was examined at the molecular level using symmetry adapted perturbation theory (SAPT) and density functional techniques through comparison of interaction energies of noncovalently bound complexes between the CO2 molecule and a series of ionic liquid ions and ion pairs. These energies were contrasted with those for complexes with model amines such as methylamine, dimethylamine, and trimethylamine. Detailed analysis of the five fundamental forces that are responsible for stabilization of the complexes is discussed. It was confirmed that the nature of the anion had a greater effect upon the physical interaction energy in non functionalized ionic liquids, with dispersion forces playing an important role in CO2 solubility. Hydrogen bonding with protic cations was shown to impart additional stability to the noncovalently bound CO2...IL complex through inductive forces. Two solvation models, the conductor-like polarizable continuum model (CPCM) and the universal solvation model (SMD), were used to estimate the impact of solvent effects on the CO2 binding. Both solvent models reduced interaction energies for all types of ions. These interaction energies appeared to favor imidazolium cations and carboxylic and sulfonic groups as well as bulky groups (e.g., NTf2) in anions for the physical absorption of CO2. The structure-reactivity relationships determined in this study may help in the optimization of the physical absorption process by means of ionic liquids. PMID- 26267785 TI - Incorrectly Classified Article. PMID- 26267782 TI - Cell traction in collective cell migration and morphogenesis: the chase and run mechanism. AB - Directional collective cell migration plays an important role in development, physiology, and disease. An increasing number of studies revealed key aspects of how cells coordinate their movement through distances surpassing several cell diameters. While physical modeling and measurements of forces during collective cell movements helped to reveal key mechanisms, most of these studies focus on tightly connected epithelial cultures. Less is known about collective migration of mesenchymal cells. A typical example of such behavior is the migration of the neural crest cells, which migrate large distances as a group. A recent study revealed that this persistent migration is aided by the interaction between the neural crest and the neighboring placode cells, whereby neural crest chase the placodes via chemotaxis, but upon contact both populations undergo contact inhibition of locomotion and a rapid reorganization of cellular traction. The resulting asymmetric traction field of the placodes forces them to run away from the chasers. We argue that this chase and run interaction may not be specific only to the neural crest system, but could serve as the underlying mechanism for several morphogenetic processes involving collective cell migration. PMID- 26267786 TI - Error in Funding/Support. PMID- 26267787 TI - Acid-Mediated Formation of Radicals or Baeyer-Villiger Oxidation from Criegee Adducts. AB - The acid-mediated reaction of ketones with hydroperoxides generates radicals, a process with reaction conditions similar to those of the Baeyer-Villiger oxidation but with an outcome resembling the formation of hydroxyl radicals via ozonolysis in the atmosphere. The Baeyer-Villiger oxidation forms esters from ketones, with the preferred use of peracids. In contrast, alkyl hydroperoxides and hydrogen peroxide react with ketones by condensation to form alkenyl peroxides, which rapidly undergo homolytic O-O bond cleavage to form radicals. Both reactions are believed to proceed via Criegee adducts, but the electronic nature of the peroxide residue determines the subsequent reaction pathways. DFT calculations and experimental results support the idea that, unlike previously assumed, the Baeyer-Villiger reaction is not intrinsically difficult with alkyl hydroperoxides and hydrogen peroxide but rather that the alternative radical formation is increasingly favored. PMID- 26267788 TI - Splenectomy Improves Hemostatic and Liver Functions in Hepatosplenic Schistosomiasis Mansoni. AB - BACKGROUND: Schistosomiasis mansoni is a chronic liver disease, in which some patients (5-10%) progress to the most severe form, hepatosplenic schistosomiasis. This form is associated with portal hypertension and splenomegaly, and often episodes of gastrointestinal bleeding, even with liver function preserved. Splenectomy is a validated procedure to reduce portal hypertension following digestive bleeding. Here, we evaluate beneficial effects of splenectomy on blood coagulation factors and liver function tests in hepatosplenic schistosomiasis mansoni compared to non-operated patients. METHODOLOGY/PRINCIPAL FINDINGS: Forty five patients who had undergone splenectomy surgery were assessed by laboratory analyses and ultrasound examination and compared to a non-operated group (n = 55). Blood samples were obtained for liver function tests, platelet count and prothrombin time. Coagulation factors (II, VII, VIII, IX and X), protein C and antithrombin IIa, plasminogen activator inhibitor-1 were measured by routine photometric, chromogenic or enzyme-linked immunosorbent assays, while hyperfibrinolysis was defined by plasminogen activator inhibitor-1 levels. Both groups had similar age, gender and pattern of periportal fibrosis. Splenectomized patients showed significant reductions in portal vein diameter, alkaline phosphatase and bilirubin levels compared to non-operated patients, while for coagulation factors there were significant improvement in prothrombin, partial thromboplastin times and higher levels of factor VII, VIII, IX, X, protein C and plasminogen activator inhibitor-1. CONCLUSION/SIGNIFICANCE: This study shows that the decrease of flow pressure in portal circulation after splenectomy restores the capacity of hepatocyte synthesis, especially on the factor VII and protein C levels, and these findings suggest that portal hypertension in patients with hepatosplenic schistosomiasis influences liver functioning and the blood coagulation status. PMID- 26267789 TI - Enhancing Macrophage Drug Delivery Efficiency via Co-Localization of Cells and Drug-Loaded Microcarriers in 3D Resonant Ultrasound Field. AB - In this study, a novel synthetic 3D molecular transfer system which involved the use of model drug calcein-AM-encapsulated poly(lactic-co-glycolic acid) microspheres (CAPMs) and resonant ultrasound field (RUF) with frequency of 1 MHz and output intensity of 0.5 W/cm2 for macrophage drug delivery was explored. We hypothesized that the efficiency of CAPMs-mediated drug delivery aided by RUF can be promoted by increasing the contact opportunities between cells and the micrometer-sized drug carriers due to effects of acoustic radiation forces generated by RUF. Through the fluoromicroscopic and flow cytometric analyses, our results showed that both DH82 macrophages and CAPMs can be quickly brought to acoustic pressure nodes within 20 sec under RUF exposure, and were consequently aggregated throughout the time course. The efficacy of cellular uptake of CAPMs was enhanced with increased RUF exposure time where a 3-fold augmentation (P < 0.05) was obtained after 15 min of RUF exposure. We further demonstrated that the enhanced CAPM delivery efficiency was mainly contributed by the co-localization of cells and CAPMs resulting from the application of the RUF, rather than from sonoporation. In summary, the developed molecular delivery approach provides a feasible means for macrophage drug delivery. PMID- 26267790 TI - Structural Basis for Substrate and Oxygen Activation in Homoprotocatechuate 2,3 Dioxygenase: Roles of Conserved Active Site Histidine 200. AB - Kinetic and spectroscopic studies have shown that the conserved active site residue His200 of the extradiol ring-cleaving homoprotocatechuate 2,3-dioxygenase (FeHPCD) from Brevibacterium fuscum is critical for efficient catalysis. The roles played by this residue are probed here by analysis of the steady-state kinetics, pH dependence, and X-ray crystal structures of the FeHPCD position 200 variants His200Asn, His200Gln, and His200Glu alone and in complex with three catecholic substrates (homoprotocatechuate, 4-sulfonylcatechol, and 4 nitrocatechol) possessing substituents with different inductive capacity. Structures determined at 1.35-1.75 A resolution show that there is essentially no change in overall active site architecture or substrate binding mode for these variants when compared to the structures of the wild-type enzyme and its analogous complexes. This shows that the maximal 50-fold decrease in kcat for ring cleavage, the dramatic changes in pH dependence, and the switch from ring cleavage to ring oxidation of 4-nitrocatechol by the FeHPCD variants can be attributed specifically to the properties of the altered second-sphere residue and the substrate. The results suggest that proton transfer is necessary for catalysis, and that it occurs most efficiently when the substrate provides the proton and His200 serves as a catalyst. However, in the absence of an available substrate proton, a defined proton-transfer pathway in the protein can be utilized. Changes in the steric bulk and charge of the residue at position 200 appear to be capable of altering the rate-limiting step in catalysis and, perhaps, the nature of the reactive species. PMID- 26267792 TI - Attenuation of post-infarction remodeling in rats by sustained myocardial growth hormone administration. AB - Prevention of left ventricular remodeling is an important therapeutic target post myocardial infarction. Experimentally, treatment with growth hormone (GH) is beneficial, but sustained local administration has not been thoroughly investigated. We studied 58 rats (322 +/- 4 g). GH was administered via a biomaterial-scaffold, following in vitro and in vivo evaluation of degradation and drug-release curves. Treatment consisted of intra-myocardial injection of saline or alginate-hydrogel, with or without GH, 10 min after permanent coronary artery ligation. Echocardiographic and histologic remodeling-indices were examined 3 weeks post-ligation, followed by immunohistochemical evaluation of angiogenesis, collagen, macrophages and myofibroblasts. GH-release completed at 3 days and alginate-degradation at ~7 days. Alginate + GH consistently improved left ventricular end-diastolic and end-systolic diameters, ventricular sphericity, wall tension index and infarct-thickness. Microvascular-density and myofibroblast-count in the infarct and peri-infarct areas were higher after alginate + GH. Macrophage-count and collagen-content did not differ between groups. Early, sustained GH-administration enhances angiogenesis and myofibroblast-activation and ameliorates post-infarction remodeling. PMID- 26267791 TI - Two single amino acid substitutions in the intervening region of Newcastle disease virus HN protein attenuate viral replication and pathogenicity. AB - Among the proteins encoded by Newcastle disease virus (NDV), the attachment protein (HN) is an important determinant of virulence and pathogenicity. HN has been molecularly characterized at the protein level; however, the relationship between the molecular character of HN and the animal pathotype it causes has not been well explored. Here, we revisited the intervening region (IR) of the HN stalk and extended the known biological functions of HN. Three distinct substitutions (A89Q, P93A, and L94A) in the IR of genotype VII NDV (G7 strain) HN protein were analyzed. The A89Q and L94A mutations weakened the fusion promotion activity of HN to 44% and 41% of that of wild type, respectively, whereas P93A decreased the neuraminidase activity to 21% of the parental level. At the virus level, P93A and L94A-bearing viruses displayed impaired receptor recognition ability, neuraminidase activity, and fusion-promoting activity, all of which led to virus attenuation. In addition, the L94A-mutated virus showed a dramatic decline in replication and was attenuated in cells and in chickens. Our data demonstrate that the HN biological activities and functions modulated by these specific amino acids in the IR are associated with NDV replication and pathogenicity. PMID- 26267793 TI - Photochromic Diarylethenes with Heterocyclic Aromatic Rings: Correlation between Thermal Bistability and Geometrical Characters of Transition States. AB - We present a density functional theory study on the thermal bistability of a number of photochromic diarylethenes, with emphasis on the free energy barrier of the ground-state ring-opening process. We found that the free energy barrier is correlated with the geometrical and vibrational character of the transition state, in particular the distance between the two reactive carbon atoms, the out of-plane angles of the methyl groups at the reactive carbon atoms, and the imaginary vibrational frequency. Based on these relationships we propose a linear fitting expression for the free energy barrier in terms of the three aforementioned transition-state quantities and obtained a correlation coefficient of R(2) = 0.971. In this way quantum chemical calculations may provide insight and structure-property relationships, which can be applied in the development of novel photochromic materials. PMID- 26267794 TI - Organisational Factors Induce Prolonged Emergency Department Length of Stay in Elderly Patients--A Retrospective Cohort Study. AB - STUDY OBJECTIVE: To assess the association of patient and organisational factors with emergency department length of stay (ED-LOS) in elderly ED patients (226565 years old) and in younger patients (<65 years old). METHODS: A retrospective cohort study of internal medicine patients visiting the emergency department between September 1st 2010 and August 31st 2011 was performed. All emergency department visits by internal medicine patients 226565 years old and a random sample of internal medicine patients <65 years old were included. Organisational factors were defined as non-medical factors. ED-LOS is defined as the time between ED arrival and ED discharge or admission. Prolonged ED-LOS is defined as >=75th percentile of ED-LOS in the study population, which was 208 minutes. RESULTS: Data on 1782 emergency department visits by elderly patients and 597 emergency department visits by younger patients were analysed. Prolonged ED-LOS in elderly patients was associated with three organisational factors: >1 consultation during the emergency department visit (odds ratio (OR) 3.2, 95% confidence interval (CI) 2.3-4.3), a higher number of diagnostic tests (OR 1.2, 95% CI 1.16-1.33) and evaluation by a medical student or non-trainee resident compared with a medical specialist (OR 4.2, 95% CI 2.0-8.8 and OR 2.3, 95% CI 1.4 3.9). In younger patients, prolonged ED-LOS was associated with >1 consultation (OR 2.6, 95% CI 1.4-4.6). Factors associated with shorter ED-LOS were arrival during nights or weekends as well as a high urgency level in elderly patients and self-referral in younger patients. CONCLUSION: Organisational factors, such as a higher number of consultations and tests in the emergency department and a lower seniority of the physician, were the main aspects associated with prolonged ED LOS in elderly patients. Optimisation of the organisation and coordination of emergency care is important to accommodate the needs of the continuously growing number of elderly patients in a better way. PMID- 26267795 TI - Impact of placental Plasmodium falciparum malaria on the profile of some oxidative stress biomarkers in women living in Yaounde, Cameroon. AB - BACKGROUND: Impact of the pathophysiology of Plasmodium falciparum placental malaria (PM) on the profile of some oxidative stress biomarkers and their relationship with poor pregnancy outcomes in women remain unknown. METHODS: Between 2013 and 2014, peripheral blood and placenta tissue from 120 Cameroonian women at delivery were assessed for maternal haemoglobin and, parasitaemia respectively. Parasite accumulation in the placenta was investigated histologically. The levels of oxidative stress biomarkers Malondialdehyde (MDA), Nitric Oxide (NO), Superoxide dismutase (SOD), Catalase (CAT) and Gluthatione (GSH) in the supernatant of teased placenta tissues were determined by Colorimetric enzymatic assays. RESULTS: Parasitaemia was inversely related to haemoglobin levels and birth weight (P <0.001 and 0.012, respectively). The level of lipid peroxide product (MDA) was significantly higher in the malaria infected (P = 0.0047) and anaemic (P = 0.024) women compared to their non-infected and non anaemic counterparts, respectively. A similar trend was observed with SOD levels, though not significant. The levels of MDA also correlated positively with parasitaemia (P = 0.0024) but negatively with haemoglobin levels (P = 0.002). There was no association between parasitaemia, haemoglobin level and the other oxidative stress biomarkers. From histological studies, levels of MDA associated positively and significantly with placenta malaria infection and the presence of malaria pigments. The levels of SOD, NO and CAT increased with decreasing leukocyte accumulation in the intervillous space. Baby birth weight increased significantly with SOD and CAT levels, but decreased with levels of GSH. CONCLUSIONS: Placental P. falciparum infection may cause oxidative stress of the placenta tissue with MDA as a potential biomarker of PM, which alongside GSH could lead to poor pregnancy outcomes (anaemia and low birth weight). This finding contributes to the understanding of the pathophysiology of P. falciparum placental malaria in women. PMID- 26267796 TI - Conservation hotspots for the turtles on the high seas of the Atlantic Ocean. AB - Understanding the distribution of bycaught sea turtles could inform conservation strategies and priorities. This research analyses the distribution of turtles caught as longline fisheries bycatch on the high seas of the Atlantic Ocean. This research collected 18,142 bycatch observations and 47.1 million hooks from large scale Taiwanese longline vessels in the Atlantic Ocean from June 2002 to December 2013. The coverage rates were ranged from 0.48% to 17.54% by year. Seven hundred and sixty-seven turtles were caught, and the major species were leatherback (59.8%), olive ridley (27.1%) and loggerhead turtles (8.7%). Most olive ridley (81.7%) and loggerhead (82.1%) turtles were hooked, while the leatherbacks were both hooked (44.0%) and entangled (31.8%). Depending on the species, 21.4% to 57.7% were dead when brought onboard. Most of the turtles were caught in tropical areas, especially in the Gulf of Guinea (15 degrees N-10 degrees S, 30 degrees W 10 degrees E), but loggerheads were caught in the south Atlantic Ocean (25 degrees S-35 degrees S, 40 degrees W-10 degrees E and 30 degrees S-40 degrees S, 55 degrees W-45 degrees W). The bycatch rate was the highest at 0.030 per 1000 hooks for leatherbacks in the tropical area. The bycatch rates of olive ridley ranged from 0 to 0.010 per thousand hooks. The loggerhead bycatch rates were higher in the northern and southern Atlantic Ocean and ranged from 0.0128 to 0.0239 per thousand hooks. Due to the characteristics of the Taiwanese deep-set longline fleet, bycatch rates were lower than those of coastal longline fisheries, but mortality rates were higher because of the long hours of operation. Gear and bait modification should be considered to reduce sea turtle bycatch and increase survival rates while reducing the use of shallow hooks would also be helpful. PMID- 26267797 TI - Consumption of dental treatment in patients with inflammatory bowel disease, a register study. AB - OBJECTIVE: The aim of this study was to compare the consumption of dental treatment among patients with Crohn's disease (CD) or ulcerative colitis (UC) compared to age and gender matched control groups. DESIGN: The study group comprised 2085 patients with CD and 3161 with UC from the Uppsala-Orebro region and from the Stockholm region. The patients in the cohort were diagnosed between 1960 and 1989. Patients up to 70 years of age were included in the study. The two patients groups were compared to age- and gender-matched, randomly selected control groups from the same geographic area comprising a corresponding number of participants. RESULTS: CD patients had significantly higher total number of procedures registered (p < 0.000). The difference was most pronounced for removable dentures (+65%), fillings in front teeth (+52%) and endodontic treatment (+46%) when Crohn's patients were compared to controls (p<0.001). The corresponding figures for UC patients were also a significantly higher total number of procedures (p < 0.005), more clinical examinations (p<0.000), fillings in canines and incisors (p < 0.001) and fillings in bicuspids and molars (p < 0.000). CONCLUSION: This study demonstrate that CD and UC individuals use more dental treatment compared to an age-gender matched control group, and more caries related treatments. The difference was most pronounced for restorative treatment in patients with Crohn's. PMID- 26267798 TI - Effect of Chemical Structure on Polymer-Templated Growth of Graphitic Nanoribbons. AB - Graphene nanoribbon (GNR) is an important candidate for future nanoelectronics due to its high carrier mobility and dimension-controlled band gap. Polymer templated growth is a promising method toward high quality and massive production of GNRs. However, the obtained GNRs so far are still quite defective. In order to rationally control the crystallinity of the synthesized GNRs, herein we systematically investigate the effect of polymer chemical structure on their templated growth of GNRs. We studied the morphology/dimensions, composition, graphitization degree, and electrical conductivity of GNRs derived from four different types of electrospun polymers. The four polymers polystyrene (PS), poly(vinyl alcohol) (PVA), polyvinylphenol (PVP), and Novolac (a phenolic resin) are chosen to investigate the effect of metal binding and the effect of aromatic moieties. We found that metal-binding functional groups are crucial for obtaining uniform and continuous GNRs. On the other hand, a polymer with aromatic moieties leads to a higher sp(2) percentage in the resulting GNRs, showing a higher graphitization degree and electrical conductivity. PMID- 26267799 TI - Discovery of Novel, Potent, and Specific Cell-Death Inducers in the Jurkat Acute Lymphoblastic Leukemia Cell Line. AB - The limited clinical efficacy of many cancer therapeutics has initiated intense research efforts toward the discovery of novel chemical entities in this field. In this study, 31 hit candidates were selected from nearly 800,000 database compounds in a ligand-based virtual screening campaign. In turn, three of these hits were found to have (sub)micromolar potencies in proliferation assays with the Jurkat acute lymphatic leukemic cell line. In this assay, the three hits were found to exhibit higher potency than clinically tested cell-death inducers (GDC 0152, AT-406, and birinapant). Importantly, antiproliferative activity toward non cancer peripheral blood mononuclear cells (PBMCs) was found to be marginal. Further biological characterization demonstrated the cell-death-inducing properties of these compounds. Biological testing of hit congeners excluded a nonspecific, toxic effect of the novel structures. Altogether, these findings may have profound relevance for the development of clinical candidates in tumor therapy. PMID- 26267800 TI - Correction: Brain Extraction Using Label Propagation and Group Agreement: Pincram. PMID- 26267801 TI - Diagnostic Support for Selected Paediatric Pulmonary Diseases Using Answer Pattern Recognition in Questionnaires Based on Combined Data Mining Applications- A Monocentric Observational Pilot Study. AB - BACKGROUND: Clinical symptoms in children with pulmonary diseases are frequently non-specific. Rare diseases such as primary ciliary dyskinesia (PCD), cystic fibrosis (CF) or protracted bacterial bronchitis (PBB) can be easily missed at the general practitioner (GP). OBJECTIVE: To develop and test a questionnaire based and data mining-supported tool providing diagnostic support for selected pulmonary diseases. METHODS: First, interviews with parents of affected children were conducted and analysed. These parental observations during the pre diagnostic time formed the basis for a new questionnaire addressing the parents' view on the disease. Secondly, parents with a sick child (e.g. PCD, PBB) answered the questionnaire and a data base was set up. Finally, a computer program consisting of eight different classifiers (support vector machine (SVM), artificial neural network (ANN), fuzzy rule-based, random forest, logistic regression, linear discriminant analysis, naive Bayes and nearest neighbour) and an ensemble classifier was developed and trained to categorise any given new questionnaire and suggest a diagnosis. For estimating the diagnostic accuracy, we applied ten-fold stratified cross validation. RESULTS: All questionnaires of patients suffering from CF, asthma (AS), PCD, acute bronchitis (AB) and the healthy control group were correctly diagnosed by the fusion algorithm. For the pneumonia (PM) group 19/21 (90.5%) and for the PBB group 17/18 (94.4%) correct diagnoses could be reached. The program detected the correct diagnoses with an overall sensitivity of 98.8%. Receiver operating characteristics (ROC) analyses confirmed the accuracy of this diagnostic tool. Case studies highlighted the applicability of the tool in the daily work of a GP. CONCLUSION: For children with symptoms of pulmonary diseases a questionnaire-based diagnostic support tool using data mining techniques exhibited good results in arriving at diagnostic suggestions. In the hands of a doctor, this tool could be of value in arousing awareness for rare pulmonary diseases such as PCD or CF. PMID- 26267802 TI - Optimal first-line chemotherapeutic treatment in patients with locally advanced or metastatic esophagogastric carcinoma: triplet versus doublet chemotherapy: a systematic literature review and meta-analysis. AB - There is a debate whether triplet or doublet chemotherapy should be used as a first-line treatment in patients with advanced or metastatic esophagogastric cancer. Therefore, here we will review the available literature to assess the efficacy and safety of triplet versus doublet chemotherapy as a first-line treatment in patients with advanced esophagogastric cancer. We searched MEDLINE, Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) between 1980 and March 2015 for randomized controlled phase II and III trials comparing triplet with doublet chemotherapy and abstracts of major oncology meetings from 1990 to 2014. Twenty-one studies with a total of 3475 participants were included in the meta-analysis for overall survival. An improvement in overall survival (OS) (hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.83-0.97) and progression-free survival (PFS) (HR 0.80, 95% CI 0.69-0.93) was observed in favor of triplet. In addition, the use of triplet was associated with better objective response rate (ORR) (risk ratio 1.25, 95% CI 1.09-1.44) compared to doublet. The risks of grade 3-4 thrombocytopenia (6.2 vs 3.8%), infection (10.2 vs 6.4%), and mucositis (9.7 vs 4.7%) were statistically significantly increased with triplet compared to doublet. This review shows that first-line triplet therapy is superior to doublet therapy in patients with advanced esophagogastric cancer. However, the survival benefit is limited and the risks of grade 3-4 thrombocytopenia, infection, and mucositis are increased. PMID- 26267803 TI - The importance of radiotherapy on diffuse large B cell lymphoma treatment: a current review. AB - Diffuse large B cell lymphoma is recognized as a heterogeneous group of hematological malignancies; two main subtypes germinal center B and activated B cells are well defined although 15% of patients remain with unclassifiable disease. R-CHOP treatment has proven to provide very effective results in limited or advanced stage of the disease. However, treatment solely involving R-CHOP submits the patient to possible chemotherapy-induced toxicities, which may be avoided with the use of radiotherapy. Patients with early stage localized disease or who are particularly unresponsive to chemotherapy may be more suitable for mixed modality treatment with R-CHOP and consolidative radiotherapy. Although radiotherapy is being slowly phased out by other treatment strategies including chemotherapy and therapeutic drugs, it is still a highly important method of treatment. The different forms of radiotherapy can be used alongside these "new age" treatment strategies to further improve prognostic outcomes and overall survival rates. The establishment of radiotherapy as a treatment strategy provides a highly beneficial prognostic advantage in early stage, localized disease. PMID- 26267804 TI - Activity-Based Proteomic Profiling of Deubiquitinating Enzymes in Salmonella Infected Macrophages Leads to Identification of Putative Function of UCH-L5 in Inflammasome Regulation. AB - Although protein ubiquitination has been shown to regulate multiple processes during host response to Salmonella enterica serovar Typhimurium infection, specific functions of host deubiquitinating enzymes remain unknown in this bacterial infection. By using chemical proteomics approach, in which deubiquitinating enzymes were labeled by an active-site probe and analyzed by quantitative proteomics, we identified novel deubiquitinases in chicken macrophages based on their reactivity with the probe. Also, we detected down regulation of UCH-L3, and USP4 as well as up-regulation of USP5 and UCH-L5 deubiquitinating enzymes in macrophages infected with Salmonella Typhimurium. We showed that decrease in either UCH-L5 activity, or in UCH-L5 protein amount in chicken and human macrophages infected or stimulated with LPS/nigericin, led to decreased IL-1beta release. These data point towards a putative role of UCH-L5 in inflammasome regulation during Salmonella infection. Because inflammasome activation is important in innate resistance to these bacteria, one would expect that naturally occurring or therapeutically induced alteration in UCH-L5 activation would influence disease outcome and could represent a target for new therapeutic approaches. PMID- 26267805 TI - Hint-seeking behaviour of western scrub-jays in a metacognition task. AB - Metacognitive processes during memory retrieval can be tested by examining whether or not animals can assess their knowledge state when they are faced with a memory test. In a typical foraging task, food is hidden in one of the multiple tubes and the subjects are given an opportunity to check the contents of the tubes before choosing the one that they thought contained food. Following the findings from our previous study that western scrub-jays (Aphelocoma californica) can make prospective metacognition judgements, this study tested the scrub-jays' concurrent metacognition judgements. In a series of experiments, uncertainty about the food location was induced in three ways: by making the baiting process visibly unavailable, by inserting a delay between the baiting and food retrieval, and by moving the location of the bait. The jays looked into the tubes more often during the conditions that were consistent with high uncertainty. In addition, their looking behaviour was associated not with the sight of food but with information about the location of the food. These findings suggest that the jays can differentiate the states of knowing and not knowing about certain information and take appropriate action to complement their missing knowledge. PMID- 26267806 TI - Microsomal Triglyceride Transfer Protein (MTP) Associates with Cytosolic Lipid Droplets in 3T3-L1 Adipocytes. AB - Lipid droplets are intracellular energy storage organelles composed of a hydrophobic core of neutral lipid, surrounded by a monolayer of phospholipid and a diverse array of proteins. The function of the vast majority of these proteins with regard to the formation and/or turnover of lipid droplets is unknown. Our laboratory was the first to report that microsomal triglyceride transfer protein (MTP), a lipid transfer protein essential for the assembly of triglyceride-rich lipoproteins, was expressed in adipose tissue of humans and mice. In addition, our studies suggested that MTP was associated with lipid droplets in both brown and white fat. Our observations led us to hypothesize that MTP plays a key role in lipid droplet formation and/or turnover. The objective of these studies was to gain insight into the function of MTP in adipocytes. Using molecular, biochemical, and morphologic approaches we have shown: 1) MTP protein levels increase nearly five-fold as 3T3-L1 cells differentiate into adipocytes. 2) As 3T3-L1 cells undergo differentiation, MTP moves from the juxtanuclear region of the cell to the surface of lipid droplets. MTP and perilipin 2, a major lipid droplet surface protein, are found on the same droplets; however, MTP does not co localize with perilipin 2. 3) Inhibition of MTP activity has no effect on the movement of triglyceride out of the cell either as a lipid complex or via lipolysis. 4) MTP is found associated with lipid droplets within hepatocytes from human fatty livers, suggesting that association of MTP with lipid droplets is not restricted to adipocytes. In summary, our data demonstrate that MTP is a lipid droplet-associated protein. Its location on the surface of the droplet in adipocytes and hepatocytes, coupled with its known function as a lipid transfer protein and its increased expression during adipocyte differentiation suggest a role in lipid droplet biology. PMID- 26267807 TI - Flow-Based Assembly of Layer-by-Layer Capsules through Tangential Flow Filtration. AB - Layer-by-layer (LbL) assembly on nano- and microparticles is of interest for a range of applications, including catalysis, optics, sensors, and drug delivery. One current limitation is the standard use of manual, centrifugation-based (pellet/resuspension) methods to perform the layering steps, which can make scalable, highly controllable, and automatable production difficult to achieve. Here, we develop a fully flow-based technique using tangential flow filtration (TFF) for LbL assembly on particles. We demonstrate that multilayered particles and capsules with different sizes (from micrometers to submicrometers in diameter) can be assembled on different templates (e.g., silica and calcium carbonate) using several polymers (e.g., poly(allylamine hydrochloride), poly(styrenesulfonate), and poly(diallyldimethylammonium chloride)). The full system only contains fluidic components routinely used (and automated) in industry, such as pumps, tanks, valves, and tubing in addition to the TFF filter modules. Using the TFF LbL system, we also demonstrate the centrifugation-free assembly, including core dissolution, of drug-loaded capsules. The well controlled, integrated, and automatable nature of the TFF LbL system provides scientific, engineering, and practical processing benefits, making it valuable for research environments and potentially useful for translating LbL assembled particles into diverse applications. PMID- 26267808 TI - Prostate cancer gene 3 (PCA3) is of additional predictive value in patients with PI-RADS grade III (intermediate) lesions in the MR-guided re-biopsy setting for prostate cancer. AB - PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) improves diagnostic accuracy in re-biopsies of men with prostate cancer (PC) suspicion, but predictive value is limited despite the use of the new Prostate Imaging Reporting and Data System (PI-RADS). Prognostic value of the PC-specific biomarker prostate cancer gene 3 (PCA3) added to the PI-RADS score was evaluated. METHODS: The study was a retrospective analysis of the institutional database for men with MR-guided biopsy (MR-GB) for suspicious lesion in mpMRI and who had an additional pre-MR-GB PCA3 testing for ongoing PC suspicion. All men had >= 1 negative ultrasound GB. Lesions were retrospectively scored by PI-RADS in three MRI sequences (T2w, DCE, and DWI). PCA3 was analyzed with cutoffs of 25 and 35. The prognostic value of mpMRI and PCA3 and the additional value of both were explored. RESULTS: Tumor detection rate (49 men, mean PSA 10 ng/ml, lesion size 40 mm(2)) was 45 % (22/49 patients). In the subgroup of PI-RADS IV degrees , 17/17 patients had PC; in PI RADS III degrees (intermediate) 5/15 had PC, and all 5 had a PCA3 > 35. PCA3 > 35 had no additional prognostic value in the whole cohort. Out of the 10/15 PC negative patients (PI-RADS III degrees ), PCA3 was < 35 in 6. The inclusion of PCA3 value in PI-RADS III degrees patients improved predictive accuracy to 91.8 %. CONCLUSION: MpMRI and subsequent grading to PI-RADS significantly improves PC detection in the re-biopsy setting. The diagnostic uncertainty in the PI-RADS intermediate group can be ameliorated by the addition of PCA3 cutoff of 35 to avoid potential unnecessary biopsies. PMID- 26267809 TI - A simple and effective method for vegetative propagation of an endangered medicinal plant Salacia oblonga Wall. AB - Salacia oblonga Wall. is an endangered medicinal plant whose conservation is urgently needed, as it is extensively used in the Indian Ayurvedic system of medicine to treat diabetes mellitus. This study shows an easy, effective and simple method of conserving genetic identity and producing elite clones of S. oblonga through vegetative propagation. Vegetative propagation was achieved using roots (R), stems with leaves (SL) and stems without leaves (S) with different concentrations (0-500 ppm) of indole butyric acid (IBA). Explants S and SL showed maximum shooting response with 300 ppm IBA and explant R showed maximum response with 200 ppm IBA. PMID- 26267810 TI - Callicarpa longissima extract, carnosol-rich, potently inhibits melanogenesis in B16F10 melanoma cells. AB - Cosmetic industries focus on developing materials and resources that regulate skin pigmentation. Melanin, the major pigment in human skin, protects the skin against damage from ultraviolet light. An ethanolic extract of the leaves of Callicarpa longissima inhibits melanin production in B16F10 mouse melanoma cells by suppressing microphthalmia-associated transcription factor (MITF) gene expression. Following purification and analysis using liquid chromatography-mass spectrometry (LC-MS), NMR, and biochemical assays, carnosol was determined to be responsible for the major inhibitory effect of the C. longissima extract on melanin production. Carnosol is an oxidative product of carnosic acid, whose presence in the extract was also confirmed by an authentic reference. The carnosol and carnosic acid content in the extract was approximately 16% (w/w). These results suggest that C. longissima is a novel, useful, and attractive source of skin-whitening agents. PMID- 26267812 TI - Single-Crystal-to-Single-Crystal Transition in an Enantiopure [7]Helquat Salt: The First Observation of a Reversible Phase Transition in a Helicene-Like Compound. AB - Here it is reported that crystals of an enantiopure [7]helquat salt undergo reversible thermal solid-solid phase transition at 404 K. Differential scanning calorimetry (DSC), capillary electrophoresis (CE), and X-ray diffraction analysis were used to unravel the mechanistic details of this process. The single-crystal to-single-crystal course enabled direct monitoring of the structural changes by in situ variable-temperature X-ray diffraction, thus providing the first direct evidence of a solid phase transition in a helicene-like compound. PMID- 26267811 TI - 1-Methyl-D-tryptophan potentiates TGF-beta-induced epithelial-mesenchymal transition in T24 human bladder cancer cells. AB - Immune escape and metastasis are the hallmarks of several types of cancer including bladder cancer. One of the mechanisms involved in these processes has been linked to indoleamine 2,3-dioxygenase (IDO). Although IDO is classically recognized for its immunomodulatory property, it has presented nonimmunological effects in some tumors. TGF-beta1 is believed to contribute to carcinoma development by modulating immunossupressive molecules, including IDO. In addition, TGF-beta1 induces the epithelial-mesenchymal transition (EMT), which is a critical step in the tumor invasiveness and metastasis. We investigated the role of MT and IDO modulation in the induction of EMT by TGF-beta1 in T24 human bladder carcinoma cells. When T24 cells were incubated with the IDO inhibitor (MT, 1-methyl-D-tryptophan), with TGF-beta1, and with MT+TGF-beta1, a significant decrease of IDO expression and activity was observed. In addition, downregulation of e-cadherin and upregulation of n-cadherin and EMT transcription factors were induced by the treatments, confirming the induction of EMT. siRNA-mediated knockdown of IDO decreased e-cadherin expression, but had no effect on EMT transcription factors. In the scratch-wound assay, the heightened migration process was intensified when the cells were incubated with MT+TGF-beta1. These effects were associated with a robust inhibition of Akt activation. After inoculation of T24 cells under the kidney capsule of Balb/c nude, the cells were positive for IDO in the center of the cell infiltrate, being negative in the periphery, where EMT is high. In conclusion, inhibition of IDO by TGF-beta1 and MT is associated with EMT in T24 human bladder carcinoma cells. MT has potentiating effect in TGF-beta1-induced EMT, independently of IDO. This nonimmunological effect of MT should be considered if IDO is the target to avoid immune escape in bladder cancer. PMID- 26267813 TI - Effects of Land Use on Lake Nutrients: The Importance of Scale, Hydrologic Connectivity, and Region. AB - Catchment land uses, particularly agriculture and urban uses, have long been recognized as major drivers of nutrient concentrations in surface waters. However, few simple models have been developed that relate the amount of catchment land use to downstream freshwater nutrients. Nor are existing models applicable to large numbers of freshwaters across broad spatial extents such as regions or continents. This research aims to increase model performance by exploring three factors that affect the relationship between land use and downstream nutrients in freshwater: the spatial extent for measuring land use, hydrologic connectivity, and the regional differences in both the amount of nutrients and effects of land use on them. We quantified the effects of these three factors that relate land use to lake total phosphorus (TP) and total nitrogen (TN) in 346 north temperate lakes in 7 regions in Michigan, USA. We used a linear mixed modeling framework to examine the importance of spatial extent, lake hydrologic class, and region on models with individual lake nutrients as the response variable, and individual land use types as the predictor variables. Our modeling approach was chosen to avoid problems of multi-collinearity among predictor variables and a lack of independence of lakes within regions, both of which are common problems in broad-scale analyses of freshwaters. We found that all three factors influence land use-lake nutrient relationships. The strongest evidence was for the effect of lake hydrologic connectivity, followed by region, and finally, the spatial extent of land use measurements. Incorporating these three factors into relatively simple models of land use effects on lake nutrients should help to improve predictions and understanding of land use-lake nutrient interactions at broad scales. PMID- 26267815 TI - Controlled Self-Assembly of Hexagonal Nanoparticle Patterns on Nanotopographies. AB - Diblock copolymer micelle nanolithography (BCML) is a versatile and efficient method to cover large surface areas with hexagonally ordered arrays of metal nanoparticles, in which the nanoparticles are equally spaced. However, this method falls short of providing a controlled allocation of such regular nanoparticle arrays with specific spacing into micropatterns. We present here a quick and high-throughput method to generate quasi-hexagonal nanoparticle structures with well-defined interparticle spacing on segments of nanotopographic Si substrates. The topographic height of these segments plays a dominant role in dictating the spacing between the gold nanoparticles, as the nanoparticle arrangement is controlled by immersion forces and by their self-assembly within the segments. Our novel strategy of employing a single-step BCML routine is a highly promising method for the fabrication of regular gold nanopatterns in micropatterns for a wide range of applications. PMID- 26267814 TI - Tsetse Control and Gambian Sleeping Sickness; Implications for Control Strategy. AB - BACKGROUND: Gambian sleeping sickness (human African trypanosomiasis, HAT) outbreaks are brought under control by case detection and treatment although it is recognised that this typically only reaches about 75% of the population. Vector control is capable of completely interrupting HAT transmission but is not used because it is considered too expensive and difficult to organise in resource poor settings. We conducted a full scale field trial of a refined vector control technology to determine its utility in control of Gambian HAT. METHODS AND FINDINGS: The major vector of Gambian HAT is the tsetse fly Glossina fuscipes which lives in the humid zone immediately adjacent to water bodies. From a series of preliminary trials we determined the number of tiny targets required to reduce G. fuscipes populations by more than 90%. Using these data for model calibration we predicted we needed a target density of 20 per linear km of river in riverine savannah to achieve >90% tsetse control. We then carried out a full scale, 500 km2 field trial covering two HAT foci in Northern Uganda to determine the efficacy of tiny targets (overall target density 5.7/km2). In 12 months, tsetse populations declined by more than 90%. As a guide we used a published HAT transmission model and calculated that a 72% reduction in tsetse population is required to stop transmission in those settings. INTERPRETATION: The Ugandan census suggests population density in the HAT foci is approximately 500 per km2. The estimated cost for a single round of active case detection (excluding treatment), covering 80% of the population, is US$433,333 (WHO figures). One year of vector control organised within the country, which can completely stop HAT transmission, would cost US$42,700. The case for adding this method of vector control to case detection and treatment is strong. We outline how such a component could be organised. PMID- 26267816 TI - Health outcomes in US children with abdominal pain at major emergency departments associated with race and socioeconomic status. AB - OBJECTIVE: Over 9.6 million ED visits occur annually for abdominal pain in the US, but little is known about the medical outcomes of these patients based on demographics. We aimed to identify disparities in outcomes among children presenting to the ED with abdominal pain linked to race and SES. METHODS: Data from 4.2 million pediatric encounters of abdominal pain were analyzed from 43 tertiary US children's hospitals, including 2.0 million encounters in the emergency department during 2004-2011. Abdominal pain was categorized as functional or organic abdominal pain. Appendicitis (with and without perforation) was used as a surrogate for abdominal pain requiring emergent care. Multivariate analysis estimated likelihood of hospitalizations, radiologic imaging, ICU admissions, appendicitis, appendicitis with perforation, and time to surgery and hospital discharge. RESULTS: Black and low income children had increased odds of perforated appendicitis (aOR, 1.42, 95% CI, 1.32- 1.53; aOR, 1.20, 95% CI 1.14 - 1.25). Blacks had increased odds of an ICU admission (aOR, 1.92, 95% CI 1.53 - 2.42) and longer lengths of stay (aHR, 0.91, 95% CI 0.86 - 0.96) than Whites. Minorities and low income also had lower rates of imaging for their appendicitis, including CT scans. The combined effect of race and income on perforated appendicitis, hospitalization, and time to surgery was greater than either separately. CONCLUSIONS: Based on race and SES, disparity of health outcomes exists in the acute ED setting among children presenting with abdominal pain, with differences in appendicitis with perforation, length of stay, and time until surgery. PMID- 26267817 TI - Immunogenicity and sustainability of the immune response in Brazilian HIV-1 infected individuals vaccinated with inactivated triple influenza vaccine. AB - HIV-infected individuals have a higher risk of serious illnesses following infection by infection with influenza. Although anti-influenza vaccination is recommended, immunosuppression may limit their response to active immunization. We followed-up a cohort of HIV-infected individuals vaccinated against influenza to assess the immunogenicity and sustainability of the immune response to vaccination. Individuals were vaccinated 2011 with inactivated triple influenza vaccine (TIV), and they had received in 2010 the monovalent anti-A(H1N1)pdm09 vaccine. The sustainability of the immune response to A(H1N1)pdm09 at 12 months after monovalent vaccination fell, both in individuals given two single or two double doses. For these individuals, A(H1N1)pdm09 component from TIV acted as a booster, raising around 40% the number of seroprotected individuals. Almost 70% of the HIV-infected individuals were already seroprotected to A/H3N2 at baseline. Again, TIV boosted over 90% the seroprotection to A/H3N2. Anti-A/H3N2 titers dropped by 20% at 6 months after vaccination. Pre-vaccination seroprotection rate to influenza B (victoria lineage) was the lowest among those tested, seroconversion rates were higher after vaccination. Seroconversion/protection after TIV vaccination did not differ significantly across categories of clinical and demographic variables. Anti-influenza responses in Brazilian HIV-infected individuals reflected both the previous history of virus circulation in Brazil and vaccination. PMID- 26267818 TI - Protective effects of tartary buckwheat flavonoids on high TMAO diet-induced vascular dysfunction and liver injury in mice. AB - This study was performed to investigate the liver and vascular changes in high trimethylamine-N-oxide (TMAO) diet-fed mice, and the possible vasoprotective and hepatoprotective effects of purified tartary buckwheat flavonoid fraction (TBF). HPLC analysis revealed that the content of rutin and quercetin presented in TBF was 53.6% and 37.2%, respectively, accounting for 90.8% of TBF. Mice fed 1.5% TMAO in drinking water for 8 weeks significantly displayed vascular dysfunction and liver damage (p < 0.01). The administration of TBF at 400 and 800 mg per kg bw significantly elevated plasma NO and eNOS concentrations, and serum HDL-C and PGI2 levels, and lowered serum TC, TG, LDL-C, ET-1 and TX-A2 levels of TMAO-fed mice. TBF also reduced serum AST and ALT activities, and hepatic NEFA and MDA levels, and increased the hepatic GSH-Px and SOD activities in TMAO-fed mice, which were consistent with the observations of the histological alterations of the liver. This report firstly showed that dietary TMAO might cause liver damage and TBF prevented TMAO-induced vascular dysfunction and hepatic injury. PMID- 26267819 TI - [Treatment of elderly with chronic pain in geriatric care and pain therapy facilities in Germany. Survey results]. AB - BACKGROUND: Even though there are no satisfactory data available on the prevalence of chronic pain in the elderly, it is certainly a common problem in Germany. The goal of this study is to provide information on the treatment of elderly patients with chronic pain in geriatric care and pain therapy facilities in Germany. METHOD: Throughout Germany geriatric and pain clinics were asked by email about their treatment practice of patients with chronic pain. The questions related to four types of patients sharing the same chronic pain characteristics and comorbidities but differing with respect to cognitive and physical impairment. The questions were divided into the following areas: equipment, staff, patient care, documentation, and cooperation. RESULTS: Replies from a total of 85 institutions were evaluated. The response rates were approximately 5 % for geriatric units and 10 % for pain units. More patients with chronic pain are treated in geriatrics units than in pain therapy facilities due to larger capacities. Although all four types of patients are treated in both types of facilities, the functionally more competent patients are more common in pain therapy facilities. In geriatrics, the inverse relationship was found. Differences exist in the staff structure and qualification, frequency and refinement of individual and group therapies, assessments used, teamwork, documentation, and cooperation with outpatient care. CONCLUSION: Due to the differences between geriatric and pain management departments shown in all investigated areas, an exchange between these two cross-sectional subjects could help to improve inpatient, outpatient and intersectoral treatment of elderly patients with chronic pain. PMID- 26267820 TI - National Trends in Ambulatory Surgery for Intervertebral Disc Disorders and Spinal Stenosis: A 12-Year Analysis of the National Surveys of Ambulatory Surgery. AB - STUDY DESIGN: A descriptive epidemiology study. OBJECTIVE: The aim of this study is to investigate changes in the utilization of ambulatory surgical procedures performed for intervertebral disc disorders and spinal stenosis between 1994 and 2006 in the United States. SUMMARY OF BACKGROUND DATA: Understanding trends in the utilization of ambulatory spine surgery may improve health care delivery in the Unites States. Epidemiologic studies evaluating national practice patterns for ambulatory spine surgery are limited. METHODS: The National Survey of Ambulatory Surgery conducted in 1994, 1996, and 2006 by the Centers for Disease Control and Prevention was analyzed to identify surgically managed patients with intervertebral disc disorders and spinal stenosis. Patients were divided into 1 of 3 groups: discectomy, laminectomy, or fusion. The data were analyzed for trends in demographics, treatment, and utilization. RESULTS: Between 1994 and 2006, the number of procedures increased by 540% for intervertebral disc disorders (6.1/100 000 capita to 34.2/100 000 capita) and 926% for spinal stenosis (0.38/100 000 capita to 3.46 per 100 000 capita). Intervertebral fusions increased from 5% of outpatient spine surgeries in 1994 to 17% in 2006. The utilization of freestanding ambulatory facilities as the location of surgery increased 340% for intervertebral disc disorders and more than 2000% for stenosis. Private insurance was the largest compensator, representing 91% of cases in 2006. An increasing proportion of females underwent surgery for intervertebral disc disorders and stenosis at these ambulatory facilities over this time period. Lumbar disc displacement remained the most common diagnosis at each time point. CONCLUSIONS: The rate of ambulatory surgery for intervertebral disc disorders and spinal stenosis increased dramatically between 1994 and 2006 based upon the National Survey of Ambulatory Surgery data, which are the most up to-date ambulatory surgery data available. These findings may aid policy-makers and caregivers in allocating health care resources to ensure the delivery of quality patient care. LEVEL OF EVIDENCE: N/A. PMID- 26267821 TI - Immediate Effects of Use of Recombinant Bone Morphogenetic Protein in Children Having Spinal Fusion and Refusion Procedures in United States. AB - STUDY DESIGN: Retrospective study of Nationwide Inpatient Sample (NIS). OBJECTIVE: The objective of this study is to estimate the prevalence of complications in children who had insertion of recombinant human bone morphogenetic protein (rhBMP) at the time of spinal fusion procedures (SFP) and to examine if the use of rhBMP is associated with an increased risk of complications. SUMMARY OF BACKGROUND DATA: Use of rhBMP for SFP has been associated with conflicting safety profile reports in adults. METHODS: NIS (years 2004-2010) was used. All patients with age < 18 years who had a SFP during hospitalization with or without insertion of rhBMP were selected. Complications were selected based on a literature review of studies examining outcomes of SFP. Association between insertion of rhBMP and occurrence of complications was examined by multivariable logistic regression models. RESULTS: Of the 72,898 children who underwent SFP, 7.1% children had insertion of rhBMP. Overall complication rate was 14.34% (15.2% in rhBMP group and 14.3% in no-rhBMP group). There was no statistically significant difference in the overall complication rate [odds ratio (OR) = 1.08, 95% confidence intervals (CI) = 0.89-1.30] or among 14 different complications between rhBMP and no-rhBMP groups. Children who had rhBMP were associated with higher odds for "other infections" (OR = 2.09, 95% CI = 1.26-3.48, P = 0.004) when compared with their counterparts. CONCLUSION: Despite the lack of Food and Drug Administration approval, rhBMP was not infrequently used in pediatric SFP. In this large retrospective study using administrative data, the use of rhBMP in children during SFP was not associated with higher risks for majority of assessed complications with the exception of "other infections". Future studies must examine the long-term impact of use of rhBMP in children with SFP. LEVEL OF EVIDENCE: 3. PMID- 26267822 TI - Change in Abdominal Morphology After Surgical Correction of Thoracolumbar Kyphosis Secondary to Ankylosing Spondylitis: A Computed Tomographic Study. AB - STUDY DESIGN: A computed tomographic study. OBJECTIVE: To investigate the change in abdominal morphology in surgically treated patients with ankylosing spondylitis (AS) and thoracolumbar kyphosis. SUMMARY OF BACKGROUND DATA: Severe thoracolumbar kyphosis in patients with AS exerts pressure on the abdominal cavity and subsequently causes intra-abdominal complications. Several spinal osteotomy techniques have been widely used to correct AS-related thoracolumbar kyphosis. To date, the changed abdominal morphology in patients with AS undergoing surgical correction of thoracolumbar kyphosis has not been addressed. METHODS: A total of 29 patients with AS undergoing lumbar pedicle subtraction osteotomy for correction of thoracolumbar kyphosis were retrospectively reviewed. Computed tomographic scans of the spine were used to measure the longitudinal, transverse, and anterior-posterior diameters of the abdominal cavity. Furthermore, the abdominal cavity was considered as an ellipsoid structure, thereby allowing calculation of its volume. Radiographical evaluations included global kyphosis (GK), thoracic kyphosis, lumbar lordosis (LL), and angle of fusion levels (AFL). RESULTS: The longitudinal diameter of abdominal cavity significantly increased (P < 0.01), whereas the transverse and anterior-posterior diameters of the abdominal cavity did not change, postoperatively (P > 0.05). Significant changes in GK, LL, and AFL were observed (P < 0.01). The abdominal cavity volume (ACV) increased by an average of 652 mL. The change in ACV was significantly correlated with the changes in GK (r = 0.453, P = 0.014), LL (r = 0.42, P = 0.023), and AFL (r = 0.388, P = 0.037). CONCLUSION: The increased ACV after correction of thoracolumbar kyphosis was quantitatively confirmed by this study. Thus, the improvement in digestive function after correction of thoracolumbar kyphosis secondary to AS, which has been previously documented, may be because of an increase in ACV. Moreover, spine surgeons should be aware of the potential risk for the development of abdominal complications caused by the lengthening of longitudinal diameter of the abdominal cavity. LEVEL OF EVIDENCE: 3. PMID- 26267823 TI - Primary Versus Revision Surgery in the Setting of Adult Spinal Deformity: A Nationwide Study on 10,912 Patients. AB - STUDY DESIGN: Retrospective review of a prospectively collected database. OBJECTIVE: This study compares patient demographics, incidence of comorbidities, procedure-related complications, and mortality following primary versus revision adult spinal deformity surgery SUMMARY OF BACKGROUND DATA.: Although adult spinal deformity (ASD) surgery has been extensively investigated, no previous study has provided nationwide estimates of patient characteristics and procedure-related complications for primary versus revision spinal deformity surgery comparatively. METHODS: Nationwide Inpatient Sample data collected between 2001 and 2010 was analyzed. Discharges with procedural codes for anterior and/or posterior thoracic and/or lumbar spinal fusion and refusion were included for patients aged 25+ and 4+ levels fused with any diagnoses specific for scoliosis. Patient demographics, comorbidity, and procedure-related complications incidence were determined for primary versus revision cohorts. Multivariate analysis reported as (OR [95% CI]). RESULTS: Discharges for 9133 primary and 850 revision cases were identified. Patients differed on the basis of demographic and hospital data. Average comorbidity indices for the cohorts were similar (P = 0.580), as was in-hospital mortality (P = 0.163). The incidence of procedure-related complications was higher for the revision cohort (46.96 % vs. 71.97%, P = 0.001). The mean hospital course for the revision cohort was longer (6.37 vs. 7.13 days, P < 0.0001). Revisions had an increased risk of complications involving the nervous system (1.34[1.10-1.6]), hematoma/seroma formation (2.31[1.92-2.78]), accidental vessel or nerve puncture (1.44[1.29-1.61]), wound dehiscence (2.18[1.48-3.21]), postop infection (3.10[2.50-3.85]), and ARDS complications (1.43[1.28-1.60]). The primary cohort had a decreased risk for GI (0.65[0.55-0.76]) and GU complications (0.71[0.51-0.99]). CONCLUSION: Relative to primary cases, those undergoing revision correction of spinal deformity have a higher risk of many procedure related complications with a longer hospital course despite similar baseline comorbidity burden and the in-hospital mortality rate. This study provides clinically useful data for surgeons to educate patients at risk for morbidity and mortality and direct future research to improve outcomes. PMID- 26267824 TI - Surgical Stabilization Improves Survival of Spinal Fractures Related to Ankylosing Spondylitis. AB - STUDY DESIGN: National registry cohort study. OBJECTIVE: The aim of this study was to investigate the effect of surgical stabilization on survival of spinal fractures related to ankylosing spondylitis (AS). SUMMARY OF BACKGROUND DATA: Spinal fractures related to AS are associated with considerable morbidity and mortality. Multiple studies suggest a beneficial effect of surgical stabilization in these patients. METHODS: In the Swedish patient registry, all patients treated in an inpatient facility are registered with diagnosis and treatment codes. The Swedish mortality registry collects date and cause of death for all fatalities. Registry extracts of all patients with AS and spinal fractures including date of death and treatment were prepared and analyzed for epidemiological purposes. RESULTS: Seventeen thousand two hundred ninety-seven individual patients with AS were admitted to treatment facilities in Sweden between 1987 and 2011. Nine hundred ninety patients with AS (age 66 +/- 14 years) had 1131 spinal fractures, of which 534 affected cervical, 352 thoracic, and 245 lumbar vertebrae. Thirteen percent had multiple levels of injuries during the observed period. Surgically treated patients had a greater survival than those treated nonsurgically [hazard ratio (HR) 0.79, P = 0.029]. Spinal cord injury was the major factor contributing to mortality in this cohort (HR 1.55, P < 0.001). The proportion of surgically treated spinal fractures increased linearly during the last decades (r = 0.92, P < 0.001) and was 64% throughout the observed years. CONCLUSIONS: Spinal cord injury threatened the survival of patients with spinal fractures related to AS. Even though surgical treatment is associated with a considerable complication rate, it improved the survival of spinal fractures related to AS. LEVEL OF EVIDENCE: 3. PMID- 26267825 TI - Treating Huge Tear-Drop Fracture of Axis With Trapezoidal Bone: A Case Report and Literature Review. AB - STUDY DESIGN: Case report and review of relevant literature. OBJECTIVE: To discuss the surgical strategies and clinical outcome of managing huge tear drop fracture of axis. SUMMARY OF BACKGROUND DATA: Teardrop fracture of axis is rarely seen, especially the huge type. The surgical technique is demanding because of the special anatomical structure and difficulty with bone grafting. Moreover, the surgical approach is controversial in the literature. METHODS: A 51-year-old male patient suffered from neck pain after falling from the bicycle, neck movement was limited with no neurological compromise. X-ray suggested huge tear-drop fracture of anterior-inferior corner of axis, narrowing of C2/3 intervertebral disc. Fusion with self-designed tricortical trapezoidal iliac bone was performed. RESULTS: Treating huge teardrop fracture of axis by anterior bone grafting with self-designed tricortical trapezoidal iliac bone is effective and stable. A 3 month follow-up showed fusion was achieved, upper cervical curvature was restored, and neck pain disappeared. CONCLUSION: Self-designed tricortical trapezoidal iliac bone provided adequate fusion area of bone grafting, restoring the normal intervertebral height and cervical alignment, and the midterm outcome is satisfactory. LEVEL OF EVIDENCE: 5. PMID- 26267826 TI - Comparison of Surgical Outcomes Between Anterior Fusion and Posterior Fusion in Patients With AIS Lenke Type 1 or 2 that Underwent Selective Thoracic Fusion Long-term Follow-up Study Longer Than 10 Postoperative Years. AB - STUDY DESIGN: A retrospective comparative study. OBJECTIVE: We compared the outcomes between patients treated either by selective thoracic anterior (ASF) or posterior spinal fusion (PSF), with a minimum 10-year follow-up. SUMMARY OF BACKGROUND DATA: A retrospective long-term follow-up study was conducted to compare PSF (P group) and ASF (A group) with Lenke type 1 or 2. There were no significant differences in the correction rate and incidence of degenerative discs (DDs) on the lumbar area. Loss of correction was greater in the A group. METHODS: The inclusion criteria were female, AIS Lenke type 1 or 2, minimum 10 year follow-up, MRI check-up at 5 years and 10 years postop. The number of patients, age, and curve types at the time of surgery were matched in both groups. Complications, pulmonary function, and SRS-30 were also evaluated. RESULTS: P group: adding-on (AO) occurred in 14 patients. Two patients demonstrated progression of scoliosis >5 degrees during follow-up. Degenerative discs occurred in 43% of patients at 10 years postop. There were significant differences in the %VC and FVC before surgery and at the final visit (P < 0.05). A group: AO occurred in 16 patients. Eleven showed progression of scoliosis >5 degrees . Degenerative disc was recognized in 53% of the patients. There was no significant difference in the pulmonary function. There was a significant difference in selfimage score in the SRS-30 between the two groups (P < 0.05). CONCLUSION: Correction of scoliosis was significantly better ASF than PSF immediately postop. Greater loss of correction occurred with ASF at postop 10 years. Although shorter segments could be fused by ASF, there was no significant difference in the incidence of DDs. Pulmonary function test results improved in the P group and were restored in the A group during the perioperative period. PMID- 26267827 TI - Minimally Invasive Pedicle Screw Fixation Using Intraoperative 3-dimensional Fluoroscopy-based Navigation (CAMISS Technique) for Hangman Fracture. AB - STUDY DESIGN: Retrospective comparative cohort series. OBJECTIVE: To evaluate the accuracy and feasibility of minimally invasive surgical (MIS) techniques incorporating with intraoperative 3-dimensional fluoroscopy-based navigation (ITFN) for treating Hangman fracture. SUMMARY OF BACKGROUND DATA: MIS screw fixation for Hangman fracture can decrease iatrogenic soft-tissue injury, but increase the risk of instrumentation-related complications due to lack of anatomical landmarks. With the advantages of obtaining intraoperative real-time images, automatic registration, and 3-dimensional views, the ITFN system seems to be an inherent partner for MIS. METHODS: 20 patients with Hangman fracture underwent C2-C3 pedicle screw fixation using ITFN. 6 patients used MIS technique, with the other 14 patients using conventional open technique. Operative time and blood loss were recorded. The accuracy of screw positions was studied by postoperative CT scan. Neck pain visual analogue score (VAS) was evaluated and the fusion status was ascertained in 6-month follow-up. RESULTS: The average operative time was 134.2 +/- 8.0 minutes in computer-assisted orthopaedics surgery (CAOS)-MIS group and 139.3 +/- 25.8 minutes in CAOS-open group (P > 0.01). The blood loss was 66.7 +/- 25.8 mL in CAOS-MIS group and 250.0 +/- 141.4 mL in CAOS-open group (P < 0.01). A total of 80 screws were inserted. No screw related neurovascular injury was observed. 83.3% (20/24) screws in CAOS-MIS group and 89.3% (50/56) screws in CAOS-open group were grade 1 screw (P > 0.01). No grade 3 screw was detected in both groups. Compared with the CAOS-open group (1.7 +/- 0.6), neck pain VAS in 6-month follow-up in CAOS-MIS group (0.3 +/- 0.5) was significantly lower (P < 0.01). Solid fusion was demonstrated in all the cases. CONCLUSION: The integration of these 2 techniques MIS and ITFN, we call "computer assisted minimally invasive spinal surgery," is proved to be feasible and safe for treating Hangman fracture with the advantage of significantly reduced iatrogenic soft tissue injury. So we think CAMISS technique represents the most recent modification of spine surgery. PMID- 26267828 TI - The Successful Practice of Evidence-based Medicine May Be Contingent Upon the Methods We Use to Measure Our Interventions. PMID- 26267829 TI - Single-Cell Analyses of ESCs Reveal Alternative Pluripotent Cell States and Molecular Mechanisms that Control Self-Renewal. AB - Analyses of gene expression in single mouse embryonic stem cells (mESCs) cultured in serum and LIF revealed the presence of two distinct cell subpopulations with individual gene expression signatures. Comparisons with published data revealed that cells in the first subpopulation are phenotypically similar to cells isolated from the inner cell mass (ICM). In contrast, cells in the second subpopulation appear to be more mature. Pluripotency Gene Regulatory Network (PGRN) reconstruction based on single-cell data and published data suggested antagonistic roles for Oct4 and Nanog in the maintenance of pluripotency states. Integrated analyses of published genomic binding (ChIP) data strongly supported this observation. Certain target genes alternatively regulated by OCT4 and NANOG, such as Sall4 and Zscan10, feed back into the top hierarchical regulator Oct4. Analyses of such incoherent feedforward loops with feedback (iFFL-FB) suggest a dynamic model for the maintenance of mESC pluripotency and self-renewal. PMID- 26267830 TI - A Quantitative Proteomic Analysis of Hemogenic Endothelium Reveals Differential Regulation of Hematopoiesis by SOX17. AB - The in vitro derivation of hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) is complicated by the existence of multiple overlapping embryonic blood cell programs called primitive, erythromyeloid progenitor (EMP), and definitive. As HSCs are only generated during the definitive stage of hematopoiesis, deciphering the regulatory pathways that control the emergence of this program and identifying markers that distinguish it from the other programs are essential. To identify definitive specific pathways and marker sets, we used label-free proteomics to determine the proteome of embryo-derived and mouse embryonic stem cell-derived VE-CADHERIN(+)CD45(-) definitive hematopoietic progenitors. With this approach, we identified Stat1 as a marker that distinguishes the definitive erythroid lineage from the primitive- and EMP derived lineages. Additionally, we provide evidence that the generation of the Stat1(+) definitive lineage is dependent on Sox17. These findings establish an approach for monitoring the emergence of definitive hematopoiesis in the PSC differentiation cultures. PMID- 26267831 TI - Metrology Standards for Quantitative Imaging Biomarkers. AB - Although investigators in the imaging community have been active in developing and evaluating quantitative imaging biomarkers (QIBs), the development and implementation of QIBs have been hampered by the inconsistent or incorrect use of terminology or methods for technical performance and statistical concepts. Technical performance is an assessment of how a test performs in reference objects or subjects under controlled conditions. In this article, some of the relevant statistical concepts are reviewed, methods that can be used for evaluating and comparing QIBs are described, and some of the technical performance issues related to imaging biomarkers are discussed. More consistent and correct use of terminology and study design principles will improve clinical research, advance regulatory science, and foster better care for patients who undergo imaging studies. PMID- 26267833 TI - Molecular dynamics simulation of the conductivity mechanism of nanorod filled polymer nanocomposites. AB - We adopted molecular dynamics simulation to study the conductive property of nanorod-filled polymer nanocomposites by focusing on the effects of the interfacial interaction, aspect ratio of the fillers, external shear field, filler-filler interaction and temperature. The variation of the percolation threshold is anti N-type with increasing interfacial interaction. It decreases with an increase in the aspect ratio. At an intermediate filler-filler interaction, a minimum percolation threshold appears. The percolation threshold decreases to a plateau with temperature. At low interfacial interaction, the effect of an external shear field on the homogeneous probability is negligible; however, the directional probability increases with shear rate. Moreover, the difference in conductivity probabilities is reduced for different interfacial interactions under shear. Under shear, the decrease or increase of conductivity probability depends on the initial dispersion state. However, the steady-state conductivity is independent of the initial state for different interfacial interactions. In particular, the evolution of the conductivity network structure under shear is investigated. In short, this study may provide rational tuning methods to obtain nanorod-filled polymer nanocomposites with high conductivity. PMID- 26267832 TI - Percutaneous Radiofrequency Ablation of Colorectal Cancer Liver Metastases: Factors Affecting Outcomes--A 10-year Experience at a Single Center. AB - PURPOSE: To identify predictors of oncologic outcomes after percutaneous radiofrequency ablation (RFA) of colorectal cancer liver metastases (CLMs) and to describe and evaluate a modified clinical risk score (CRS) adapted for ablation as a patient stratification and prognostic tool. MATERIALS AND METHODS: This study consisted of a HIPAA-compliant institutional review board-approved retrospective review of data in 162 patients with 233 CLMs treated with percutaneous RFA between December 2002 and December 2012. Contrast material enhanced CT was used to assess technique effectiveness 4-8 weeks after RFA. Patients were followed up with contrast-enhanced CT every 2-4 months. Overall survival (OS) and local tumor progression-free survival (LTPFS) were calculated from the time of RFA by using the Kaplan-Meier method. Log-rank tests and Cox regression models were used for univariate and multivariate analysis to identify predictors of outcomes. RESULTS: Technique effectiveness was 94% (218 of 233). Median LTPFS was 26 months. At univariate analysis, predictors of shorter LTPFS were tumor size greater than 3 cm (P < .001), ablation margin size of 5 mm or less (P < .001), high modified CRS (P = .009), male sex (P = .03), and no history of prior hepatectomy (P = .04) or hepatic arterial infusion chemotherapy (P = .01). At multivariate analysis, only tumor size greater than 3 cm (P = .01) and margin size of 5 mm or less (P < .001) were independent predictors of shorter LTPFS. Median and 5-year OS were 36 months and 31%. At univariate analysis, predictors of shorter OS were tumor size larger than 3 cm (P = .005), carcinoembryonic antigen level greater than 30 ng/mL (P = .003), high modified CRS (P = .02), and extrahepatic disease (EHD) (P < .001). At multivariate analysis, tumor size greater than 3 cm (P = .006) and more than one site of EHD (P < .001) were independent predictors of shorter OS. CONCLUSION: Tumor size of less than 3 cm and ablation margins greater than 5 mm are essential for satisfactory local tumor control. Tumor size of more than 3 cm and the presence of more than one site of EHD are associated with shorter OS. PMID- 26267834 TI - The role of the body in social cognition. AB - In this review, we discuss the actual and active dependence of social cognitive processes on the body, i.e., that part of the organism beyond the central nervous system. In particular, we will discuss mirror mechanisms, and assess the extent to which the body is recruited during these processes. We show that for emotion mirroring, this dependency is well-documented, but for action mirroring far less so. By reviewing these mechanisms and processes while contrasting body from brain, and social from general cognition, we show that both contrasts are arbitrary and problematic and that any study of cognitive processes, both social and general, should take the body into account. PMID- 26267836 TI - Pardon My French. PMID- 26267835 TI - Detection of Common, Emerging and Uncommon VP4, and VP7 Human Group A Rotavirus Genotypes from Urban Sewage Samples in Uruguay. AB - Environmental approach has proven to be a useful tool for epidemiological studies demonstrating through environmental studies the diversity of viruses circulating in a given population. The aim of this study was to perform a phylogenetic characterization of the group A rotavirus (RVA) glycoprotein (G)- and protease sensitive (P)-genotypes obtained from sewage samples (n = 116) collected in six cities of Uruguay during March 2011 to April 2013. A worldwide standardized semi nested multiplex RT-PCR (SNM RT-PCR) protocol directed against VP4 and VP7 genes were conducted for RVA detection and consensual DNA fragments were submitted to nucleotide sequencing. P and/or G genotype was successfully determined by phylogenetic analysis in 61% (n = 37) of the positive samples obtained by SNM RT PCR (n = 61). The RVA genotypes were as follow: G1 (n = 2), G2 (n = 14), G3 (n = 5), G12 (n = 2), P[4] (n = 4), P[8] (n = 16), and P[3] (n = 2). Interestingly, through phylogenetic analysis, emerging, and uncommon human genotypes could be detected. Results obtained from the comparison of RVA genotypes detected in the current study and Uruguayan RVA strains previously described for contemporary clinical pediatric cases showed that monitoring sewage may be a good screening option for a rapid and economical overview of the circulating genotypes in the surrounding human population and a useful approximation to study RVA epidemiology in a future vaccine monitoring program. The present study represents the first report in Uruguay that describes the phylogenetic diversity of RVA from urban sewage samples. PMID- 26267837 TI - Enzyme induction and histopathology elucidate aryl hydrocarbon receptor-mediated versus non-aryl hydrocarbon receptor-mediated effects of Aroclor 1268 in American mink (Neovison vison). AB - Polychlorinated biphenyl (PCB) concentrations reported in preferred prey and blubber of bottlenose dolphins from the Turtle-Brunswick River estuary (Georgia, USA) suggest the potential for adverse effects. However, PCBs in Turtle-Brunswick River estuary dolphins are primarily derived from Aroclor 1268, and predicting toxic effects of Aroclor 1268 is uncertain because of the mixture's unique composition and associated physiochemical characteristics. These differences suggest that toxicity benchmarks for other PCB mixtures may not be relevant to dolphins exposed to Aroclor 1268. American mink (Neovison vison) were used as a surrogate model for cetaceans to characterize mechanisms of action associated with Aroclor 1268 exposure. Mink share similarities in phylogeny and life history with cetaceans and are characteristically sensitive to PCBs, making them an attractive surrogate species for marine mammals in ecotoxicity studies. Adult female mink and a subsequent F1 generation were exposed to Aroclor 1268 through diet, and effects on enzyme induction, histopathology, thyroid hormone regulation, hematology, organ weights, and body condition index were compared to a negative control and a 3,3',4,4',5-pentachlorobiphenyl (PCB 126)-positive control. Aroclor 1268 dietary exposure concentrations ranged from 1.8 ug/g wet weight to 29 ug/g wet weight. Anemia, hypothyroidism, and hepatomegaly were observed in mink exposed to Aroclor 1268 beyond various dietary thresholds. Cytochrome P450 induction and squamous epithelial proliferation jaw lesions were low in Aroclor 1268 treatments relative to the positive control. Differences in enzyme induction and the development of squamous epithelial proliferation jaw lesions between Aroclor 1268 treatments and the positive control, coupled with effects observed in Aroclor 1268 treatments not observed in the positive control, indicate that mechanisms additional to the aryl hydrocarbon receptor-mediated pathway are associated with Aroclor 1268 exposure. PMID- 26267838 TI - Knowledge of healthcare professionals about rights of patient's images. AB - Objective To assess knowledge of healthcare professionals about capture and reproduction of images of patients in a hospital setting. Methods A cross sectional and observational study among 360 healthcare professionals (nursing staff, physical therapists, and physicians), working at a teaching hospital in the city of Sao Paulo (SP). A questionnaire with sociodemographic information was distributed and data were correlated to capture and reproduction of images at hospitals. Results Of the 360 respondents, 142 had captured images of patients in the last year, and 312 reported seeing other professionals taking photographs of patients. Of the participants who captured images, 61 said they used them for studies and presentation of clinical cases, and 168 professionals reported not knowing of any legislation in the Brazilian Penal Code regarding collection and use of images. Conclusion There is a gap in the training of healthcare professionals regarding the use of patient's images. It is necessary to include subjects that address this theme in the syllabus of undergraduate courses, and the healthcare organizations should regulate this issue. PMID- 26267839 TI - Does Koopmans' Paradigm for 1-Electron Oxidation Always Hold? Breakdown of IP/Eox Relationship for p-Hydroquinone Ethers and the Role of Methoxy Group Rotation. AB - Koopmans' paradigm states that electron loss occurs from HOMO, thus forming the basis for the observed linear relationships between HOMO/IP, HOMO/Eox, and IP/Eox. In cases where a molecule undergoes dramatic structural reorganization upon 1-electron oxidation, the IP/Eox relationship does not hold, and the origin of which is not understood. For example, X-ray crystallography of the neutral and cation radicals of bicyclo[2.2.1]heptane-annulated p-hydroquinone ethers ((T)HE and (M)HE) showed that they undergo electron-transfer-induced conformational reorganization and show breakdown of the IP/Eox relationship. DFT calculations revealed that Koopmans' paradigm still holds true because the electron-transfer induced subtle conformational reorganization, responsible for the breakdown of IP/Eox relationship, is also responsible for the reordering of HOMO and HOMO-1. Perceived failure of Koopmans' paradigm in cases of (T)HE and (M)HE assumes that both vertical and adiabatic electron detachments involve the same HOMO; however, this study demonstrates that the vertical ionization and adiabatic oxidation occur from different molecular orbitals due to reordering of HOMO/HOMO-1. The underpinnings of this finding will spur widespread interest in designing next generation molecules beyond HQEs, whose electronic structures can be modulated by electron-transfer-induced conformation reorganization. PMID- 26267840 TI - Protein resonance assignment at MAS frequencies approaching 100 kHz: a quantitative comparison of J-coupling and dipolar-coupling-based transfer methods. AB - We discuss the optimum experimental conditions to obtain assignment spectra for solid proteins at magic-angle spinning (MAS) frequencies around 100 kHz. We present a systematic examination of the MAS dependence of the amide proton T 2' times and a site-specific comparison of T 2' at 93 kHz versus 60 kHz MAS frequency. A quantitative analysis of transfer efficiencies of building blocks, as they are used for typical 3D experiments, was performed. To do this, we compared dipolar-coupling and J-coupling based transfer steps. The building blocks were then combined into 3D experiments for sequential resonance assignment, where we evaluated signal-to-noise ratio and information content of the different 3D spectra in order to identify the best assignment strategy. Based on this comparison, six experiments were selected to optimally assign the model protein ubiquitin, solely using spectra acquired at 93 kHz MAS. Within 3 days of instrument time, the required spectra were recorded from which the backbone resonances have been assigned to over 96%. PMID- 26267841 TI - Quantitative label-free and real-time surface-enhanced Raman scattering monitoring of reaction kinetics using self-assembled bifunctional nanoparticle arrays. AB - Although surface-enhanced Raman scattering (SERS) has proven to be an effective tool for label-free monitoring of catalytic reactions, quantitative characterization of reaction kinetics via this technique remains challenging owing to the difficulty in integrating catalytic and plasmonic activities into a single platform. In this work, we report on an easy access to highly sensitive plasmonic nanoarrays for direct and label-free monitoring of a gold-catalyzed reaction by SERS. The hierarchically structured three-dimensional assemblies, which consist of small gold catalyst nanoparticles distributed on a self assembled monolayer of larger gold nanoparticles, were formed through a simple and rapid stepwise interfacial self-assembling process (fabrication time <10 min). The well-defined interparticle distances (<1 nm) lead to efficient plasmonic coupling and ensure both catalytic and SERS-active sites exposed to the environment. Such a versatile bifunctional platform thus allows quantitative determination of the rate constant and activation energy of the catalytic reaction with SERS. PMID- 26267842 TI - Experiences and Lessons From Implementing Cohort Event Monitoring Programmes for Antimalarials in Four African Countries: Results of a Questionnaire-Based Survey. AB - INTRODUCTION: Cohort event monitoring (CEM) is an intensive method of post marketing surveillance for medicines safety. The method is based on prescription event monitoring, which began in the 1970s, and has since been adapted by WHO for monitoring the safety of medicines used in Public Health Programmes. CEM aims to capture all adverse events that occur in a defined group of patients after starting treatment with a specific medicine during the course of routine clinical practice. OBJECTIVE: The aims of this study were to describe the experiences of National Pharmacovigilance Centres (NCs) that have used CEM to monitor artemisinin-based combination therapy (ACT) for uncomplicated malaria in the African setting, to raise awareness of some of the challenges encountered during implementation and to highlight aspects of the method that require further consideration. METHOD: A questionnaire-based survey was conducted to capture the experiences of NCs that have implemented CEM for active post-marketing surveillance of antimalarial medicines in sub-Saharan Africa. Six NCs were identified as having implemented CEM programmes and were invited to participate in the survey; five NCs indicated willingness to participate and were sent the questionnaire to complete. RESULTS: Four NCs responded to the survey-Ghana, Kenya, Nigeria and Zimbabwe-providing information on the implementation of a total of six CEM programmes. Their experiences indicate that CEM has helped to build pharmacovigilance capacity within the participating NCs and at the monitoring sites, and that healthcare providers (HCPs) are generally willing to participate in implementing the CEM method. All of the programmes took longer than expected to complete: contributing factors included a prolonged enrolment period and unexpectedly slow data entry. All of the programmes exceeded their budget by 11.1-63.2 %. Data management was identified as a challenge for all participating NCs. CONCLUSIONS: The reported experiences of four NCs that have undertaken CEM studies on ACTs indicate that CEM has helped to build pharmacovigilance capacity within NCs and monitoring sites and that HCPs are willing to participate in CEM programmes; however, the method was found to be labour intensive and data management was identified as a challenge. Reducing the workload associated with CEM, particularly in relation to data management, and integrating the method into the routine work of HCPs and NCs should be considered for future implementation. PMID- 26267843 TI - Characterisation of peripheral blood mononuclear cell microRNA in hepatitis B related acute-on-chronic liver failure. AB - Hepatitis B-related acute-on-chronic liver failure (HBV-ACLF) is a life threatening condition and the mechanisms of its development and progression remain unclear. The aim of this study was to define the characteristics of peripheral blood mononuclear cell microRNAs in patients with HBV-ACLF. In this study, novel microRNA (miRNA) biomarkers of peripheral blood mononuclear cells (PBMCs) in patients with HBV-ACLF were characterised by high-throughput sequencing and validated by quantitative real-time polymerase chain reaction (qRT PCR). The results showed 78 miRNAs were significantly differentially expressed in patients with HBV-ACLF compared to patients with chronic hepatitis B (CHB) and healthy controls. Among patients with HBV-ACLF, 17 dysregulated miRNAs increased or decreased more than 4-fold, of which eight miRNAs had higher expression levels than median level. qRT-PCR validation demonstrated that six miRNAs (hsa-miR-21 5p, hsa-miR-34c-5p, hsa-miR-143-3p, hsa-miR-143-5p, hsa-miR-374a-3p and hsa-miR 542-3p) may be useful as novel biomarkers for the diagnosis of HBV-ACLF. Five novel miRNAs (L-miR-1~5) were detected and two (L-miR-1 and L-miR-3) were significantly differentially expressed in patients with HBV-ACLF. CONCLUSIONS: The miRNA expression profile of PBMCs is altered in patients with HBV-ACLF, and a signature of six miRNAs may be a promising biomarker for HBV-ACLF progression. PMID- 26267844 TI - Assessment of gastric emptying in children: Establishment of control values utilizing a standardized vegetarian meal. AB - BACKGROUND AND AIM: Disorders of gastric emptying constitute an important group of conditions in children. The diagnostic gold standard is scintigraphy, and recommendations for standardization have been published with adult normative data. Pediatric literature lacks standardized age specific normative values. Our aim was to establish normal values of solid phase gastric emptying utilizing scintigraphy in children (5-18 years) using the recommended imaging protocol and standardized meal. METHODS: Gastric emptying was assessed by scintigraphy of a (99m) Tc-labeled vegetarian meal. Image acquisition was dynamic for first hour and static at 2, 3, and 4 h. Results were reported as percent intragastric retention; lag phase defined as time to 5% emptying. RESULTS: Thirty (17 boys) healthy children, mean ages of 9.5 +/- 3.1 (range 5 to 16) years, were enrolled. Median values (5th and 95th percentiles) for percent gastric retention at 30 min, 1, 2, 3 and 4 h were 90% (76 and 100%), 77% (56 and 96%), 33% (10 and 71%), 16% (3 and 44%), and 7% (0.5 and 22%). The median (5th and 95th percentiles) lag phase was 18 min (6 and 60 min). Lag phase had no correlation with gastric retention at 4 h. CONCLUSIONS: This study provides valuable normative ranges for solid phase gastric emptying in children. Using adult normative data in children may be inappropriate. PMID- 26267845 TI - Leg pain and rash in a man with prior bariatric surgery. PMID- 26267847 TI - Clinical report: inherited deletion of chromosome 12q21.31q21.32 associated with a distinct phenotype and intellectual disability. PMID- 26267846 TI - Individual substitution mutations in the AID C terminus that ablate IgH class switch recombination. AB - Activation-induced cytidine deaminase (AID) is essential for class switch recombination (CSR) and somatic hypermutation (SHM) of Ig genes. The C terminus of AID is required for CSR but not for SHM, but the reason for this is not entirely clear. By retroviral transduction of mutant AID proteins into aid-/- mouse splenic B cells, we show that 4 amino acids within the C terminus of mouse AID, when individually mutated to specific amino acids (R190K, A192K, L196S, F198S), reduce CSR about as much or more than deletion of the entire C terminal 10 amino acids. Similar to DeltaAID, the substitutions reduce binding of UNG to Ig SMU regions and some reduce binding of Msh2, both of which are important for introducing S region DNA breaks. Junctions between the IgH donor switch (S)MU and acceptor Salpha regions from cells expressing DeltaAID or the L196S mutant show increased microhomology compared to junctions in cells expressing wild-type AID, consistent with problems during CSR and the use of alternative end-joining, rather than non-homologous end-joining (NHEJ). Unlike deletion of the AID C terminus, 3 of the substitution mutants reduce DNA double-strand breaks (DSBs) detected within the SMU region in splenic B cells undergoing CSR. Cells expressing these 3 substitution mutants also have greatly reduced mutations within unrearranged SMU regions, and they decrease with time after activation. These results might be explained by increased error-free repair, but as the C terminus has been shown to be important for recruitment of NHEJ proteins, this appears unlikely. We hypothesize that SMU DNA breaks in cells expressing these C terminus substitution mutants are poorly repaired, resulting in destruction of SMU segments that are deaminated by these mutants. This could explain why these mutants cannot undergo CSR. PMID- 26267848 TI - Spin Isomers and Ligand Isomerization in a Three-Coordinate Cobalt(I) Carbonyl Complex. AB - Hemilabile ligands, which have one donor that can reversibly bind to a metal, are widely used in transition-metal catalysts to create open coordination sites. This change in coordination at the metal can also cause spin-state changes. Here, we explore a cobalt(I) system that is poised on the brink of hemilability and of a spin-state change and can rapidly interconvert between different spin states with different structures ("spin isomers"). The new cobalt(I) monocarbonyl complex L(tBu)Co(CO) (2) is a singlet ((1)2) in the solid state, with an unprecedented diketiminate binding mode where one of the C?C double bonds of an aromatic ring completes a pseudo-square-planar coordination. Dissolving the compound gives a substantial population of the triplet ((3)2), which has exceptionally large uniaxial zero-field splitting due to strong spin-orbit coupling with a low-lying excited state. The interconversion of the two spin isomers is rapid, even at low temperature, and temperature-dependent NMR and electronic absorption spectroscopy studies show the energy differences quantitatively. Spectroscopically validated computations corroborate the presence of a low minimum-energy crossing point (MECP) between the two potential energy surfaces and elucidate the detailed pathway through which the beta-diketiminate ligand "slips" between bidentate and arene-bound forms: rather than dissociation, the cobalt slides along the aromatic system in a pathway that balances strain energy and cobalt-ligand bonding. These results show that multiple spin states are easily accessible in this hemilabile system and map the thermodynamics and mechanism of the transition. PMID- 26267849 TI - Volumetric nasal cavity analysis in children with unilateral and bilateral cleft lip and palate. AB - OBJECTIVES/HYPOTHESIS: Children with cleft lip and palate (CLP) often suffer from nasal obstruction that may be related to effects on nasal volume. The objective of this study was to compare side:side volume ratios and nasal volume in patients with unilateral (UCLP) and bilateral (BCLP) clefts with age-matched controls. STUDY DESIGN: Retrospective case-control study using three-dimensional (3D) nasal airway reconstructions. METHODS: We analyzed 20 subjects (age range = 7-12 years) with UCLP and BCLP from a regional craniofacial center who underwent cone beam computed tomography (CT) prior to alveolar grafting. Ten multislice CT images from age-matched controls were also analyzed. Mimics software (Materialise, Plymouth, MI) was used to create 3D reconstructions of the main nasal cavity and compute total and side-specific nasal volumes. Subjects imaged during active nasal cycling phases were excluded. RESULTS: There was no statistically significant difference in affected:unaffected side volume ratios in UCLP (P = .48) or left:right ratios in BCLP (P = .25) when compared to left:right ratios in controls. Mean overall nasal volumes were 9,932 +/- 1,807, 7,097 +/- 2,596, and 6,715 +/- 2,115 mm(3) for control, UCLP, and BCLP patients, respectively, with statistically significant volume decreases for both UCLP and BCLP subjects from controls (P < .05). CONCLUSIONS: This is the first study to analyze total nasal volumes in BCLP patients. Overall nasal volume is compromised in UCLP and BCLP by approximately 30%. Additionally, our finding of no major difference in side:side ratios in UCLP and BCLP compared to controls conflicts with pre-existing literature, likely due to exclusion of actively cycling scans and our measurement of the functional nasal cavity. LEVEL OF EVIDENCE: 3b. Laryngoscope, 126:1475 1480, 2016. PMID- 26267851 TI - Effect of Transcutaneous Electrical Nerve Stimulation on Plantar Flexor Muscle Spasticity and Walking Speed in Stroke Patients. AB - BACKGROUND AND PURPOSE: Spasticity is a major disabling symptom in patients post stroke. Although studies have demonstrated that transcutaneous electrical nerve stimulation (TENS) can reduce spasticity, the duration of single session TENS is a subject of debate. The purpose of this study was to determine the sustainability of the effects of TENS applied over common peroneal nerve in the reduction of ankle plantar-flexor spasticity and improving gait speed in patients post stroke. METHODS: Thirty patients (11 women and 19 men) (mean age of 46.46 years) were randomly assigned to group 1 (task oriented exercises), group 2 (TENS for 30 min and task oriented exercises) and group 3 (TENS for 60 min and task oriented exercises) for a period of five sessions per week for 6 weeks. All patients were assessed for ankle plantar-flexor spasticity, passive ankle dorsi flexion range of motion, clonus and timed up and go test at the time of recruitment to study, at 3 and 6 weeks of therapeutic intervention. RESULTS: The overall results of the study suggest that there was a decrease in ankle plantar flexor spasticity, ankle clonus and timed up and go score in all the groups. A greater reduction of spasticity was seen in TENS groups (groups 2 and 3) when compared to control. No significant improvement was found in timed up and go test (TUG) scores between groups. CONCLUSION: Both 30 min and 60 min of application of TENS are effective in reducing spasticity of ankle plantar flexors, improving walking ability and increase the effectiveness of task related training. Based on the effect size, we would recommend a longer duration application for the reduction of spasticity. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26267852 TI - Pruritic, Pink Scaling Plaques on the Face and Trunk. Pemphigus erythematosus. PMID- 26267853 TI - Effect of Three Interventions on Contact Lens Comfort in Symptomatic Wearers: A Randomized Clinical Trial. AB - PURPOSE: To investigate whether carrying out various interventions part way through the day influences comfort in symptomatic daily disposable (DD) contact lens wearers. METHODS: A subject-masked, randomized, controlled clinical trial was conducted in thirty symptomatic soft lens wearers who wore their habitual DD contact lenses bilaterally for 12 h on two separate days. Five hours after lens application, one of the following three interventions or a control was performed on each eye: replacing the existing lens with a new lens; removing and reapplying the same lens; performing a 'scleral swish'; and no action (control). Comfort scores were recorded using SMS text messages every hour following lens application using a 0 (causes pain) to 100 (excellent comfort) scale. Comfort scores before lens application, at 6 mins post-application, and at 6 mins post intervention were also recorded. RESULTS: There was a significant reduction in comfort from pre-lens application to 6 mins post-application for all groups (all p<0.05). Comfort gradually decreased from 6 mins to 5 h after lens application for each group (p<0.0001) with no significant difference between groups over the 5-h period (p = 0.09). There was no significant difference in comfort 6 mins post intervention for any group (all p>0.05). After the intervention, comfort continued to decline (p<0.0001) with slightly lower mean scores for the control group compared to the new lens group (p = 0.003). Change in comfort relative to pre-intervention (5 h) was similar for all groups (p = 0.81). There was no difference in comfort at 12 h between groups (p = 0.83). CONCLUSION: This work has confirmed that comfort shows a continual and significant decline over a 12-h wearing period in symptomatic DD contact lens wearers. None of the interventions investigated had any significant impact on end-of-day comfort. These data suggest discomfort in lens wearers is more heavily influenced by changes to the ocular environment rather than to the lens itself. TRIAL REGISTRATION: Controlled Trials.com ISRCTN10419752 http://www.controlled-trials.com/ISRCTN10419752. PMID- 26267854 TI - [Not Available]. PMID- 26267856 TI - Vulvar acanthosis with altered differentiation: is this entity a variant of hypertrophic lichen sclerosus? PMID- 26267855 TI - The Hybrid Pyrroloisoindolone-Dehydropyrrolizine Alkaloid (-)-Chlorizidine A Targets Proteins within the Glycolytic Pathway. AB - The cytotoxic activity of (-)-chlorizidine A, a marine alkaloid containing a unique fusion between a pyrroloisoindolone and dehydropyrrolizine, was explored by using a combination of cellular and molecular methods. Our studies began by applying preliminary SAR evidence gathered from semisynthetic bioactivity evaluations to prepare an active immunoaffinity fluorescent (IAF) probe. This probe was then used to identify two cytosolic proteins, GAPDH and hENO1, as the targets of (-)-chlorizidine A. PMID- 26267857 TI - An Analysis of Overstory Tree Canopy Cover in Sites Occupied by Native and Introduced Cottontails in the Northeastern United States with Recommendations for Habitat Management for New England Cottontail. AB - The New England cottontail (Sylvilagus transitionalis) is a high conservation priority in the Northeastern United States and has been listed as a candidate species under the Endangered Species Act. Loss of early successional habitat is the most common explanation for the decline of the species, which is considered to require habitat with dense low vegetation and limited overstory tree canopy. Federal and state wildlife agencies actively encourage landowners to create this habitat type by clearcutting blocks of forest. However, there are recent indications that the species also occupies sites with moderate overstory tree canopy cover. This is important because many landowners have negative views about clearcutting and are more willing to adopt silvicultural approaches that retain some overstory trees. Furthermore, it is possible that clearcuts with no overstory canopy cover may attract the eastern cottontail (S. floridanus), an introduced species with an expanding range. The objective of our study was to provide guidance for future efforts to create habitat that would be more favorable for New England cottontail than eastern cottontail in areas where the two species are sympatric. We analyzed canopy cover at 336 cottontail locations in five states using maximum entropy modelling and other statistical methods. We found that New England cottontail occupied sites with a mean overstory tree canopy cover of 58% (SE+/-1.36), and was less likely than eastern cottontail to occupy sites with lower overstory canopy cover and more likely to occupy sites with higher overstory canopy cover. Our findings suggest that silvicultural approaches that retain some overstory canopy cover may be appropriate for creating habitat for New England cottontail. We believe that our results will help inform critical management decisions for the conservation of New England cottontail, and that our methodology can be applied to analyses of habitat use of other critical wildlife species. PMID- 26267858 TI - Synthesis of 2-[(18)F]Fluoro-2-deoxyisosorbide 5-mononitrate and Assessment of Its in vivo Biodistribution as Determined by Dynamic Positron Emission Tomography (PET). AB - Herein we disclose the synthesis of 2-fluoro-2-deoxyisosorbide 5-mononitrate (2F IS-5MN), a fluorinated analogue of the commonly prescribed vasodilator isosorbide 5-mononitrate (IS-5MN). X-ray structural data for IS-5MN and its C2-epimeric congener IM-5MN are presented together with structural data for 2F-IS-5MN. Radioisotope labeling of 2F-IS-5MN has, for the first time, allowed observation of the in vivo biodistribution of this organic nitrate by means of dynamic positron emission tomography (PET) in wild-type mice. PMID- 26267860 TI - SHER: a colored petri net based random mobility model for wireless communications. AB - In wireless network research, simulation is the most imperative technique to investigate the network's behavior and validation. Wireless networks typically consist of mobile hosts; therefore, the degree of validation is influenced by the underlying mobility model, and synthetic models are implemented in simulators because real life traces are not widely available. In wireless communications, mobility is an integral part while the key role of a mobility model is to mimic the real life traveling patterns to study. The performance of routing protocols and mobility management strategies e.g. paging, registration and handoff is highly dependent to the selected mobility model. In this paper, we devise and evaluate the Show Home and Exclusive Regions (SHER), a novel two-dimensional (2 D) Colored Petri net (CPN) based formal random mobility model, which exhibits sociological behavior of a user. The model captures hotspots where a user frequently visits and spends time. Our solution eliminates six key issues of the random mobility models, i.e., sudden stops, memoryless movements, border effect, temporal dependency of velocity, pause time dependency, and speed decay in a single model. The proposed model is able to predict the future location of a mobile user and ultimately improves the performance of wireless communication networks. The model follows a uniform nodal distribution and is a mini simulator, which exhibits interesting mobility patterns. The model is also helpful to those who are not familiar with the formal modeling, and users can extract meaningful information with a single mouse-click. It is noteworthy that capturing dynamic mobility patterns through CPN is the most challenging and virulent activity of the presented research. Statistical and reachability analysis techniques are presented to elucidate and validate the performance of our proposed mobility model. The state space methods allow us to algorithmically derive the system behavior and rectify the errors of our proposed model. PMID- 26267859 TI - Eliminating anti-nutritional plant food proteins: the case of seed protease inhibitors in pea. AB - Several classes of seed proteins limit the utilisation of plant proteins in human and farm animal diets, while plant foods have much to offer to the sustainable intensification of food/feed production and to human health. Reduction or removal of these proteins could greatly enhance seed protein quality and various strategies have been used to try to achieve this with limited success. We investigated whether seed protease inhibitor mutations could be exploited to enhance seed quality, availing of induced mutant and natural Pisum germplasm collections to identify mutants, whilst acquiring an understanding of the impact of mutations on activity. A mutant (TILLING) resource developed in Pisum sativum L. (pea) and a large germplasm collection representing Pisum diversity were investigated as sources of mutations that reduce or abolish the activity of the major protease inhibitor (Bowman-Birk) class of seed protein. Of three missense mutations, predicted to affect activity of the mature trypsin / chymotrypsin inhibitor TI1 protein, a C77Y substitution in the mature mutant inhibitor abolished inhibitor activity, consistent with an absolute requirement for the disulphide bond C77-C92 for function in the native inhibitor. Two further classes of mutation (S85F, E109K) resulted in less dramatic changes to isoform or overall inhibitory activity. The alternative strategy to reduce anti-nutrients, by targeted screening of Pisum germplasm, successfully identified a single accession (Pisum elatius) as a double null mutant for the two closely linked genes encoding the TI1 and TI2 seed protease inhibitors. The P. elatius mutant has extremely low seed protease inhibitory activity and introgression of the mutation into cultivated germplasm has been achieved. The study provides new insights into structure-function relationships for protease inhibitors which impact on pea seed quality. The induced and natural germplasm variants identified provide immediate potential for either halving or abolishing the corresponding inhibitory activity, along with associated molecular markers for breeding programmes. The potential for making large changes to plant protein profiles for improved and sustainable food production through diversity is illustrated. The strategy employed here to reduce anti-nutritional proteins in seeds may be extended to allergens and other seed proteins with negative nutritional effects. Additionally, the novel variants described for pea will assist future studies of the biological role and health related properties of so-called anti-nutrients. PMID- 26267862 TI - Wild cane toads (Rhinella marina) expel foreign matter from the coelom via the urinary bladder in response to internal injury, endoparasites and disease. AB - Dissections of >1,200 wild-caught cane toads (Rhinella marina) in tropical Australia confirm a laboratory report that anurans can expel foreign objects from the coelom by incorporating them into the urinary bladder. The foreign objects that we found inside bladders included a diverse array of items (e.g., grass seeds, twigs, insect prey, parasites), many of which may have entered the coelom via rupture of the gut wall. In some cases, the urinary bladder was fused to other organs including liver, fat bodies, ovaries, Bidder's organs, lungs, mesentery, stomach wall, gall bladder, and the abdominal wall. Acanthocephalan parasites (of a range of developmental stages) were identified from the walls of the urinary bladders of three cane toads. This organ may play a significant role in destroying or excreting metazoan parasites, as well as inanimate objects. PMID- 26267861 TI - A Randomized, Double-Blind, Sham-Controlled Trial of Transcranial Direct Current Stimulation in Attention-Deficit/Hyperactivity Disorder. AB - BACKGROUND: Current standardized treatments for cognitive impairment in attention deficit/hyperactivity disorder remain limited and their efficacy restricted. Transcranial direct current stimulation (tDCS) is a promising tool for enhancing cognitive performance in several neuropsychiatric disorders. Nevertheless, the effects of tDCS in reducing cognitive impairment in patients with attention deficit/hyperactivity disorder (ADHD) have not yet been investigated. METHODS: A parallel, randomized, double-blind, sham-controlled trial was conducted to examine the efficacy of tDCS on the modulation of inhibitory control in adults with ADHD. Thirty patients were randomly allocated to each group and performed a go/no-go task before and after a single session of either anodal stimulation (1 mA) over the left dorsolateral prefrontal cortex or sham stimulation. RESULTS: A nonparametric two-sample Wilcoxon rank-sum (Mann-Whitney) test revealed no significant differences between the two groups of individuals with ADHD (tDCS vs. sham) in regard to behavioral performance in the go/no go tasks. Furthermore, the effect sizes of group differences after treatment for the primary outcome measures-correct responses, impulsivity and omission errors--were small. No adverse events resulting from stimulation were reported. CONCLUSION: According to these findings, there is no evidence in support of the use of anodal stimulation over the left dorsolateral prefrontal cortex as an approach for improving inhibitory control in ADHD patients. To the best of our knowledge, this is the first clinical study to assess the cognitive effects of tDCS in individuals with ADHD. Further research is needed to assess the clinical efficacy of tDCS in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT01968512. PMID- 26267863 TI - PEAK1 Acts as a Molecular Switch to Regulate Context-Dependent TGFbeta Responses in Breast Cancer. AB - Transforming Growth Factor beta (TGFbeta) has dual functions as both a tumor suppressor and a promoter of cancer progression within the tumor microenvironment, but the molecular mechanisms by which TGFbeta signaling switches between these outcomes and the contexts in which this switch occurs remain to be fully elucidated. We previously identified PEAK1 as a new non receptor tyrosine kinase that associates with the cytoskeleton, and facilitates signaling of HER2/Src complexes. We also showed PEAK1 functions downstream of KRas to promote tumor growth, metastasis and therapy resistance using preclinical in vivo models of human tumor progression. In the current study, we analyzed PEAK1 expression in human breast cancer samples and found PEAK1 levels correlate with mesenchymal gene expression, poor cellular differentiation and disease relapse. At the cellular level, we also observed that PEAK1 expression was highest in mesenchymal breast cancer cells, correlated with migration potential and increased in response to TGFbeta-induced epithelial-mesenchymal transition (EMT). Thus, we sought to evaluate the role of PEAK1 in the switching of TGFbeta from a tumor suppressing to tumor promoting factor. Notably, we discovered that high PEAK1 expression causes TGFbeta to lose its anti-proliferative effects, and potentiates TGFbeta-induced proliferation, EMT, cell migration and tumor metastasis in a fibronectin-dependent fashion. In the presence of fibronectin, PEAK1 caused a switching of TGFbeta signaling from its canonical Smad2/3 pathway to non-canonical Src and MAPK signaling. This report is the first to provide evidence that PEAK1 mediates signaling cross talk between TGFbeta receptors and integrin/Src/MAPK pathways and that PEAK1 is an important molecular regulator of TGFbeta-induced tumor progression and metastasis in breast cancer. Finally, PEAK1 overexpression/upregulation cooperates with TGFbeta to reduce breast cancer sensitivity to Src kinase inhibition. These findings provide a rational basis to develop therapeutic agents to target PEAK1 expression/function or upstream/downstream pathways to abrogate breast cancer progression. PMID- 26267864 TI - The Effect of Zeaxanthin on the Visual Acuity of Zebrafish. AB - Oral supplementation of carotenoids such as zeaxanthin or lutein which naturally occur in human retina have been shown to improve vision and prevent progression of damage to advanced AMD in some studies. The zebrafish eye shares many physiological similarities with the human eye and is increasingly being used as model for vision research. We hypothesized that injection of zeaxanthin into the zebrafish eye would improve the visual acuity of the zebrafish over time. Visual acuity, calculated in cycles per degree, was measured in adult zebrafish to establish a consistent baseline using the optokinetic response. Zeaxanthin dissolved into phosphate buffered saline (PBS) or PBS only was injected into the anterior chamber of the right and left eyes of the Zebrafish. Visual acuities were measured at 1 week and 3, 8 and 12 weeks post-injection to compare to baseline values. Repeated measures ANOVA was used to compare visual acuities between fish injected with PBS and zeaxanthin. A significant improvement in visual acuity, 14% better than before the injection (baseline levels), was observed one week after injection with zeaxanthin (p = 0.04). This improvement peaked at more than 30% for some fish a few weeks after the injection and improvement in vision persisted at 3 weeks after injection (p = 0.006). The enhanced visual function was not significantly better than baseline at 8 weeks (p = 0.19) and returned to baseline levels 12 weeks after the initial injection (p = 0.50). Zeaxanthin can improve visual acuity in zebrafish eyes. Further studies are required to develop a better understanding of the role zeaxanthin and other carotenoids play during normal visual function. PMID- 26267865 TI - Coordinates of Human Visual and Inertial Heading Perception. AB - Heading estimation involves both inertial and visual cues. Inertial motion is sensed by the labyrinth, somatic sensation by the body, and optic flow by the retina. Because the eye and head are mobile these stimuli are sensed relative to different reference frames and it remains unclear if a perception occurs in a common reference frame. Recent neurophysiologic evidence has suggested the reference frames remain separate even at higher levels of processing but has not addressed the resulting perception. Seven human subjects experienced a 2s, 16 cm/s translation and/or a visual stimulus corresponding with this translation. For each condition 72 stimuli (360 degrees in 5 degrees increments) were delivered in random order. After each stimulus the subject identified the perceived heading using a mechanical dial. Some trial blocks included interleaved conditions in which the influence of +/-28 degrees of gaze and/or head position were examined. The observations were fit using a two degree-of-freedom population vector decoder (PVD) model which considered the relative sensitivity to lateral motion and coordinate system offset. For visual stimuli gaze shifts caused shifts in perceived head estimates in the direction opposite the gaze shift in all subjects. These perceptual shifts averaged 13 +/- 2 degrees for eye only gaze shifts and 17 +/- 2 degrees for eye-head gaze shifts. This finding indicates visual headings are biased towards retina coordinates. Similar gaze and head direction shifts prior to inertial headings had no significant influence on heading direction. Thus inertial headings are perceived in body-centered coordinates. Combined visual and inertial stimuli yielded intermediate results. PMID- 26267866 TI - Conformational stability of the RNP domain controls fibril formation of PABPN1. AB - The disease oculopharyngeal muscular dystrophy is caused by alanine codon trinucleotide expansions in the N-terminal segment of the nuclear poly(A) binding protein PABPN1. As histochemical features of the disease, intranuclear inclusions of PABPN1 have been reported. Whereas the purified N-terminal domain of PABPN1 forms fibrils in an alanine-dependent way, fibril formation of the full-length protein occurs also in the absence of alanines. Here, we addressed the question whether the stability of the RNP domain or domain swapping within the RNP domain may add to fibril formation. A variant of full-length PABPN1 with a stabilizing disulfide bond at position 185/201 in the RNP domain fibrillized in a redox sensitive manner suggesting that the integrity of the RNP domain may contribute to fibril formation. Thermodynamic analysis of the isolated wild-type and the disulfide-linked RNP domain showed two state unfolding/refolding characteristics without detectable intermediates. Quantification of the thermodynamic stability of the mutant RNP domain pointed to an inverse correlation between fibril formation of full-length PABPN1 and the stability of the RNP domain. PMID- 26267867 TI - Cancer Incidence following Expansion of HIV Treatment in Botswana. AB - BACKGROUND: The expansion of combination antiretroviral treatment (ART) in southern Africa has dramatically reduced mortality due to AIDS-related infections, but the impact of ART on cancer incidence in the region is unknown. We sought to describe trends in cancer incidence in Botswana during implementation of the first public ART program in Africa. METHODS: We included 8479 incident cases from the Botswana National Cancer Registry during a period of significant ART expansion in Botswana, 2003-2008, when ART coverage increased from 7.3% to 82.3%. We fit Poisson models of age-adjusted cancer incidence and counts in the total population, and in an inverse probability weighted population with known HIV status, over time and estimated ART coverage. FINDINGS: During this period 61.6% of cancers were diagnosed in HIV-infected individuals and 45.4% of all cancers in men and 36.4% of all cancers in women were attributable to HIV. Age-adjusted cancer incidence decreased in the HIV infected population by 8.3% per year (95% CI -14.1 to -2.1%). However, with a progressively larger and older HIV population the annual number of cancers diagnosed remained constant (0.0% annually, 95% CI -4.3 to +4.6%). In the overall population, incidence of Kaposi's sarcoma decreased (4.6% annually, 95% CI -6.9 to -2.2), but incidence of non Hodgkin lymphoma (+11.5% annually, 95% CI +6.3 to +17.0%) and HPV-associated cancers increased (+3.9% annually, 95% CI +1.4 to +6.5%). Age-adjusted cancer incidence among individuals without HIV increased 7.5% per year (95% CI +1.4 to +15.2%). INTERPRETATION: Expansion of ART in Botswana was associated with decreased age-specific cancer risk. However, an expanding and aging population contributed to continued high numbers of incident cancers in the HIV population. Increased capacity for early detection and treatment of HIV-associated cancer needs to be a new priority for programs in Africa. PMID- 26267868 TI - Followers are not enough: a multifaceted approach to community detection in online social networks. AB - In online social media networks, individuals often have hundreds or even thousands of connections, which link these users not only to friends, associates, and colleagues, but also to news outlets, celebrities, and organizations. In these complex social networks, a 'community' as studied in the social network literature, can have very different meaning depending on the property of the network under study. Taking into account the multifaceted nature of these networks, we claim that community detection in online social networks should also be multifaceted in order to capture all of the different and valuable viewpoints of 'community.' In this paper we focus on three types of communities beyond follower-based structural communities: activity-based, topic-based, and interaction-based. We analyze a Twitter dataset using three different weightings of the structural network meant to highlight these three community types, and then infer the communities associated with these weightings. We show that interesting insights can be obtained about the complex community structure present in social networks by studying when and how these four community types give rise to similar as well as completely distinct community structure. PMID- 26267869 TI - Understanding emergent functions in self-assembled fibrous networks. AB - Understanding self-assembly processes of nanoscale building blocks and characterizing their properties are both imperative for designing new hierarchical, network materials for a wide range of structural, optoelectrical, and transport applications. Although the characterization and choices of these material building blocks have been well studied, our understanding of how to precisely program a specific morphology through self-assembly still must be significantly advanced. In the recent study by Xie et al (2015 Nanotechnology 26 205602), the self-assembly of end-functionalized nanofibres is investigated using a coarse-grained molecular model and offers fundamental insight into how to control the structural morphology of nanofibrous networks. Varying nanoscale networks are observed when the molecular interaction strength is changed and the findings suggest that self-assembly through the tuning of molecular interactions is a key strategy for designing nanostructured networks with specific topologies. PMID- 26267870 TI - You Say STD..... PMID- 26267871 TI - Patient-Reported Expedited Partner Therapy for Gonorrhea in the United States: Findings of the STD Surveillance Network 2010-2012. AB - BACKGROUND: Expedited partner therapy (EPT) has been shown to prevent reinfection in persons with gonorrhea and to plausibly reduce incidence. The Centers for Disease Control and Prevention recommends EPT as an option for treating sex partners of heterosexual patients. Few studies that examine how the reported use of this valuable intervention differs by patient and provider characteristics and by geography across multiple jurisdictions in the United States are currently available. METHODS: Case and patient interview data were obtained for a random sample of reported cases from 7 geographically disparate US jurisdictions participating in the Sexually Transmitted Disease (STD) Surveillance Network. These data were weighted to be representative of all reported gonorrhea cases in the 7 study sites. Patient receipt of EPT was estimated, and multivariate models were constructed separately to examine factors associated with receipt of EPT for heterosexuals and for men who have sex with men. RESULTS: Overall, 5.4% of patients diagnosed and reported as having gonorrhea reported receiving EPT to treat their sex partners. Heterosexual patients were more likely to have received EPT than men who have sex with men at 6.6% and 2.6% of patients, respectively. Receipt of EPT did not vary significantly by race, Hispanic ethnicity, or age for either group, although significant variation was observed in different provider settings, with patients from family planning/reproductive health and STD clinic settings more likely to report receiving EPT. Jurisdiction variations were also observed with heterosexual patients in Washington State most likely (35.5%), and those in New York City, Connecticut, and Philadelphia least likely to report receiving EPT (<2%). CONCLUSIONS: With the exception of one jurisdiction in the STD Surveillance Network actively promoting EPT use, patient-reported receipt of the intervention remains suboptimal across the network. Additional efforts to promote EPT, especially for patients diagnosed in private provider and hospital settings, are needed to realize the full potential of this valuable gonorrhea control intervention. PMID- 26267872 TI - Relationship of Specific Bacteria in the Cervical and Vaginal Microbiotas With Cervicitis. AB - BACKGROUND: Cervicitis is an inflammatory condition of the cervix associated with upper genital tract infection and reproductive complications. Although cervicitis can be caused by several known pathogens, the etiology frequently remains obscure. Here we investigate vaginal bacteria associated with bacterial vaginosis as potential causes of cervicitis. METHODS: Associations between vaginal bacteria and cervicitis were assessed in a retrospective case-control study of women attending a Seattle sexually transmitted disease clinic. Individual bacterial species were detected using 2 molecular methods: quantitative polymerase chain reaction (qPCR) and broad-range 16S rRNA gene PCR with pyrosequencing. The primary finding from this initial study was evaluated using qPCR in a second cohort of Kenyan women. RESULTS: The presence of Mageeibacillus indolicus, formerly BVAB3, in the cervix was associated with cervicitis, whereas the presence of Lactobacillus jensenii was inversely associated. Quantities of these bacteria did not differ between cervicitis cases and controls, although in a model inclusive of presence and abundance, M. indolicus remained significantly associated with cervicitis after adjustment for other cervicitis-causing pathogens. M. indolicus was not associated with cervicitis in our study of Kenyan women, possibly due to differences in the clinical definition of cervicitis. CONCLUSIONS: Colonization of the endocervix with M. indolicus may contribute to the clinical manifestations of cervicitis, but further study is needed to determine whether this finding is repeatable and applicable to diverse groups of women. Colonization of the cervix with L. jensenii could be a marker of health, perhaps reducing inflammation or inhibiting pathogenic infection. PMID- 26267873 TI - Trichomonas vaginalis Infection in a Tertiary Care Vaginitis Center. AB - BACKGROUND: Trichomonas vaginalis infection (TVI) is one of the most common sexually transmitted diseases in the United States. We sought to determine the features of TVI in a referral-based vaginitis center, focusing on diagnosis and treatment of difficult cases. METHODS: We conducted a retrospective review of all patients with TVI, based on International Classification of Diseases, Ninth Revision codes, seen at the Drexel Vaginitis Center between January 2008 and November 2013. Information collected on each subject included demographics, symptoms, examination findings, diagnostic tests, and treatment regimens. RESULTS: Of approximately 4000 new patient visits during our study period, 80 subjects were identified with TVI. Twenty subjects presented with known TVI, with most having clinically resistant infections. Diagnosis was confirmed by saline microscopy in 45%, OSOM rapid test in 40%, and clinical history in the remaining 15%. Treatment regimens varied: 20% received single 2-g dosing of either metronidazole or tinidazole, 50% received high-dose regimens, 20% received therapy with vaginal paromomycin, and 10% underwent desensitization for nitroimidazole allergy. Sixty subjects had newly diagnosed TVI, with 35% diagnosed by saline microscopy, 41.7% by OSOM rapid test, and 23.3% by APTIMA. Treatment regimens for these subjects included single 2-g dosing in 88.3%, high dose regimen in 8.3%, and other formulations in the remaining 3.4%. In total, 80% of our subjects returned for follow-up; all of whom were cured. CONCLUSIONS: T. vaginalis infection is a rare condition in a tertiary care vaginitis center and often requires nonstandard treatments. Among those who returned for follow-up, the cure rate was 100%. PMID- 26267874 TI - Self-Reported Impact of Chlamydia Testing on Subsequent Behavior: Results of an Online Survey of Young Adults in England. AB - BACKGROUND: The National Chlamydia Screening Programme performs 1.7 million tests annually among young adults in England. The effect of chlamydia screening on subsequent behavior is unknown. This study examined the self-reported impact of testing on young adults' subsequent health care-seeking and sexual behavior. METHODS: We conducted a cross-sectional Web-based anonymous survey using an online panel to recruit 1521 young adults aged 16 to 24 years and resident in England. Survey questions were developed using the theory of planned behavior. Multivariate log-binomial regression was used to identify the variables associated with an impact on subsequent behavior after testing. RESULTS: Most respondents reported that being tested for chlamydia had a positive effect on their subsequent sexual behavior (68.6%; 422/615) or health care-seeking behavior (80.0%; 492/615). In multivariate analysis, being female and having a high level of engagement at last test were both associated with positive impacts on sexual behavior (72.7% [adjusted prevalence ratio {aPR}, 1.19; 95% confidence interval {CI}, 1.07-1.33] and 82.7% [aPR, 1.55; 95% CI, 1.27-1.89], respectively), and health care-seeking behavior (84.4% [aPR, 1.13; 95% Cl, 1.04-1.24] and 86.3% [aPR, 1.23; 95% CI, 1.07-1.41], respectively). Among respondents with minimum level of engagement, 72.4% (76/105) reported an increase in subsequent health care-seeking behavior. CONCLUSIONS: Chlamydia testing had a positive impact on young adults' self-reported health care-seeking and sexual behavior. This suggests that chlamydia screening has a wider effect on young adults' sexual health beyond that of treatment alone. PMID- 26267875 TI - Oncogenic Human Papillomavirus Infections in 18- to 24-Year-Old Female Online Daters. AB - BACKGROUND: Although risk factors for HPV infections in young women are well defined, the risk associated with meeting male sex partners via the Internet is unclear. METHODS: We analyzed cross-sectional data from 282 women aged 18 to 24 years who reported using Internet dating Web sites in the past year. Women were mailed vaginal self-sampling kits for polymerase chain reaction-based HPV genotyping (including 19 oncogenic types) and sexual behavior and health history questionnaires. Generalized linear models were used to evaluate risk factors for prevalent oncogenic HPV infections. RESULTS: Thirty-five percent of women reported having met a male sex partner via the Internet in the past 6 months, and 42% reported a history of HPV vaccination. The prevalence of oncogenic HPV infection was 37%, and 9% of women tested positive for HPV-16 or HPV-18. Having met a male sex partner via the Internet in the past 6 months was not significantly associated with oncogenic HPV infection. In multivariate analyses, variables associated with an increased likelihood of oncogenic HPV infection included male partners in the past 6 months who were reported to have at least 1 concurrent partnership (adjusted prevalence ratio [aPR], 1.51; 95% confidence interval [CI], 1.11-2.06) and not always using condoms with male partners in the past 6 months (aPR, 1.86; 95% CI, 1.05-3.30). Self-reporting a history of receiving at least 1 dose of HPV vaccine was inversely associated with testing positive for HPV-16 or HPV-18 (aPR, 0.39; 95% CI, 0.16-0.97). CONCLUSIONS: Although measures of recent sexual behavior were associated with prevalent oncogenic HPV infection, male partners met online were not associated with an increased likelihood of infection in this cohort of young women. PMID- 26267876 TI - Characteristics of African American Women and Their Partners With Perceived Concurrent Partnerships in 4 Rural Counties in the Southeastern U.S. AB - BACKGROUND: To the individual with concurrent partners, it is thought that having concurrent partnerships confers no greater risk of acquiring HIV than having multiple consecutive partnerships. However, an individual whose partner has concurrent partnerships (partner's concurrency) is at increased risk for incident HIV infection. We sought to better understand relationships characterized by partner's concurrency among African American women. METHODS: A total of 1013 African American women participated in a cross-sectional survey from 4 rural Southeastern counties. RESULTS: Older age at first sex was associated with lower prevalence of partner's concurrency (prevalence ratio, 0.70; 95% confidence interval, 0.57-0.87), but the participant's age was not associated with partner's concurrency. After adjusting for covariates, ever having experienced intimate partner violence (IPV) and forced sex were most strongly associated with partner's concurrency (prevalence ratios, 1.61 [95% confidence intervals, 1.23 2.11] and 1.65 [1.20-2.26], respectively). Women in mutually monogamous partnerships were the most likely to receive economic support from their partners; women whose partners had concurrent partnerships did not report more economic benefit than did those whose partners were monogamous. CONCLUSIONS: Associations between history of IPV and forced sex with partner's concurrency suggest that women with these experiences may particularly benefit from interventions to reduce partner's concurrency in addition to support for reducing IPV and other sexual risks. To inform these interventions, further research to understand partnerships characterized by partner's concurrency is warranted. PMID- 26267877 TI - Heterogeneity of HIV Prevalence Among the Sexual Networks of Black and White Men Who Have Sex With Men in Atlanta: Illuminating a Mechanism for Increased HIV Risk for Young Black Men Who Have Sex With Men. AB - BACKGROUND: Studying the heterogeneity and correlates of HIV risk in the sexual networks of black and white men who have sex with men (MSM) may help explain racial disparities in HIV-infection. METHODS: Black and white MSM were recruited as seeds using venue-based time sampling and provided data regarding their recent sex partners. We used chain referral methods to enroll seeds' recent sex partners; newly enrolled partners in turn provided data on their recent sex partners, some of whom later enrolled. Data about unenrolled recent sex partners obtained from seeds and enrolled participants were also analyzed. We estimated the prevalence of HIV in sexual networks of MSM and assessed differential patterns of network HIV risk by the race of the seed. RESULTS: The mean network prevalence of HIV in sexual networks of black MSM (n = 117) was 36% compared with 4% in networks of white MSM (n = 78; P < 0.0001). Sexual networks of unemployed black MSM had a higher prevalence of HIV than their employed counterparts (51% vs. 29%, P = 0.007). The networks of HIV-negative black MSM seeds aged 18 to 24 years had a network prevalence of 9% compared with 2% among those aged 30 years or older. In networks originating from a black HIV-positive seed, the prevalence ranged from 63% among those aged 18 to 24 years to 80% among those 30 years or older. CONCLUSIONS: The high prevalence of HIV in the networks of HIV-negative young black MSM demonstrates a mechanism for the increased HIV incidence observed in this age group. More research is needed into how age and socioeconomic factors shape sexual networks and HIV risk. PMID- 26267878 TI - Behaviors Associated With a Risk of HIV Transmission From HIV-Positive Street Youth to Non-Street Youth in Ukraine. AB - BACKGROUND: Little is known about the extent to which HIV-infected street youth (living part or full time on the streets) exhibit behaviors associated with HIV transmission in their interactions with youth not living on the streets ("non street youth"). We aimed to determine prevalences and predictors of such "bridging behaviors": inconsistent condom use and needle sharing between HIV positive street youth and non-street youth. METHODS: A total of 171 street youth in 3 Ukrainian cites were identified as HIV infected after testing of eligible participants aged 15 to 24 years after random selection of venues. Using data from these youth, we calculated prevalence estimates of bridging behaviors and assessed predictors using logistic regression. RESULTS: Overall, two-thirds of HIV-infected street youth exhibited bridging behaviors; subgroups with high prevalences of bridging included females (78.3%) and those involved in transactional sex (84.2%). In multivariable analysis, inconsistent condom use with non-street youth was associated with being female (adjusted prevalence ratio [aPR], 1.2; 95% confidence interval [CI], 1.1-1.4), working (aPR, 1.2; 95% CI, 1.03-1.4), multiple partners (aPR, 1.4; 95% CI, 1.2-1.6), and "never" (aPR, 1.4; 95% CI, 1.1-1.6) or "sometimes" (aPR, 1.3; 95% CI, 1.02-1.8) versus "always" sleeping on the street. Needle sharing with non-street youth was associated with being male (aPR, 1.4; 95% CI, 1.02-2.0), orphaned (aPR, 2.3; 95% CI, 1.8-3.0), and 2 years or less living on the streets (aPR, 1.8; 95% CI, 1.5-2.1). CONCLUSIONS: Bridging behaviors between HIV-infected street youth and non-street youth are common. Addressing the comprehensive needs of street and other at-risk youth is a critical prevention strategy. PMID- 26267879 TI - Balanoposthitis and Penile Edema: Atypical Manifestations of Primary Syphilis. AB - The typical finding in primary syphilis stage is a unique, painless chancre with indurated borders. We report a case of primary syphilis presenting as erosive and crusted balanoposthitis with an underlying chancre, penile edema, and bilateral inguinal lymphadenopathy in a heterosexual man. PMID- 26267880 TI - Seroprevalence of Herpes Simplex Virus Type 1 and Type 2 and Coinfection With HIV and Syphilis: The First National Seroprevalence Survey in Saudi Arabia. AB - BACKGROUND: Herpes simplex virus (HSV) infection is one of the most common viral infections worldwide. Genital herpes is associated with other sexually transmitted infections (STIs) including HIV. Data on prevalence of HSV infections and other STIs in the Kingdom of Saudi Arabia are limited. METHODS: We conducted the first national seroprevalence survey to determine the prevalence and epidemiology of HSV infection among adult Saudis and coinfection with other STIs. Serology was used to detect HSV-1, HSV-2, HIV, and syphilis infections among 4985 participants recruited from across the Kingdom. RESULTS: The overall prevalence of HSV-1 and HSV-2 in the enrolled population was 88.8% and 1.26%, respectively. Although not significant for HSV-2, HSV infection was more prevalent among females, those working, and those who were married (married, divorced, or widowed), especially those married at a younger age. Prevalence of both viruses was statistically significantly higher among those with low education and increased with age. Prevalence of Treponema pallidum antibodies and HIV in the sampled population was very low (0.55% and 0.06%, respectively), as was their prevalence among HSV-2-positive participants (1.6% for both). The correlation between HSV-2 infection and other STIs was significant for HIV (P < 0.0001) but not for T. pallidum antibodies (P = 0.25). CONCLUSIONS: Herpes simplex virus type 1 infection is highly prevalent in Saudi Arabia and mostly acquired before adulthood. Herpes simplex virus type 2 prevalence is very low, acquired in adulthood, and increased with age. Monitoring the prevalence of HSV infection can help inform targeted strategies to prevent new infections, neonatal transmission, and the spread of other STIs in the Kingdom. PMID- 26267881 TI - Next-Generation Methods for HIV Partner Services: A Systematic Review. AB - Partner notification is a widely accepted method whose intent is to limit onward HIV transmission. With increasing use of new technologies such as text messaging, e-mail, and social network sites, there is growing interest in using these techniques for "next-generation" HIV partner services (PS). We conducted a systematic review to assess the use and effectiveness of these technologies in HIV PS. Our literature search resulted in 1343 citations, with 7 meeting inclusion criteria. We found programs in 2 domains: (1) Public Health Department usage of new technologies to augment traditional partner notification (n = 3) and (2) patient or provider-led usage of partner notification Web sites (n = 4) The health department-based efforts showed an ability to find new cases in a previously unreachable population but in the limited comparisons to traditional PS had a lower rate of successful contact. Usage data from the partner notification Web sites revealed a high total number of e-notifications sent, with less than 10% of cards sent for HIV. Clear evidence on outcomes and directly traceable utilization for these Web services was lacking. When given a choice, most clients chose to send e-notifications via text versus e-mail. Although successful notification may be lower overall, use of next-generation services provides an avenue to contact those who would previously have been untraceable. Additional research is needed to determine to what extent technology-enhanced PS improves the identification of newly infected persons as well as the initiation of new prevention interventions for HIV-negative clients within high-risk networks. PMID- 26267882 TI - Viral Co-infection and Leprosy Outcomes: A Cohort Study. AB - BACKGROUND: The role of the host immunity in determining leprosy clinical forms and complications is well recognized, implying that changes in the immune status may interfere with several aspects of the disease. Therefore, we hypothesized that the presence of viral co-infections and associated immunological changes will have a clinical impact on leprosy outcomes. The aim of our study was to determine the clinical impact of human immunodeficiency virus (HIV), human T cell lymphotrophic virus type 1 (HTLV-1), hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection on the development of reactions, neuritis, neuropathy and relapses. METHODOLOGY/PRINCIPAL FINDINGS: Cohort study in 245 leprosy subjects from Bahia, Brazil. Patients were followed from the time of diagnosis until at least the end of multidrug therapy. Viral co-infection was detected in 36 out of the 245 patients (14.7%). Specific co-infection rates were 10.6% for HBV, 2.9% for HIV, 2.5% for HTLV-1 and 0.8% for HCV. All four groups of co infected patients had higher rates of neuritis and nerve function impairment compared to non co-infected leprosy subjects. The relapse rate was also higher in the co-infected group (8.3%) versus patients without co-infection (1.9%); relative risk 4.37, 95% confidence interval 1.02-18.74. CONCLUSIONS/SIGNIFICANCE: Leprosy patients should be screened for HBV, HCV, HIV and HTLV-1 co-infections. Besides contributing to better health care, this measure will facilitate the early detection of severe complications through targeting of higher risk patients. PMID- 26267883 TI - The Effect of a Variable Disc Pad Friction Coefficient for the Mechanical Brake System of a Railway Vehicle. AB - A brake hardware-in-the-loop simulation (HILS) system for a railway vehicle is widely applied to estimate and validate braking performance in research studies and field tests. When we develop a simulation model for a full vehicle system, the characteristics of all components are generally properly simplified based on the understanding of each component's purpose and interaction with other components. The friction coefficient between the brake disc and the pad used in simulations has been conventionally considered constant, and the effect of a variable friction coefficient is ignored with the assumption that the variability affects the performance of the vehicle braking very little. However, the friction coefficient of a disc pad changes significantly within a range due to environmental conditions, and thus, the friction coefficient can affect the performance of the brakes considerably, especially on the wheel slide. In this paper, we apply a variable friction coefficient and analyzed the effects of the variable friction coefficient on a mechanical brake system of a railway vehicle. We introduce a mathematical formula for the variable friction coefficient in which the variable friction is represented by two variables and five parameters. The proposed formula is applied to real-time simulations using a brake HILS system, and the effectiveness of the formula is verified experimentally by testing the mechanical braking performance of the brake HILS system. PMID- 26267884 TI - The neurophysiology of language processing shapes the evolution of grammar: evidence from case marking. AB - Do principles of language processing in the brain affect the way grammar evolves over time or is language change just a matter of socio-historical contingency? While the balance of evidence has been ambiguous and controversial, we identify here a neurophysiological constraint on the processing of language that has a systematic effect on the evolution of how noun phrases are marked by case (i.e. by such contrasts as between the English base form she and the object form her). In neurophysiological experiments across diverse languages we found that during processing, participants initially interpret the first base-form noun phrase they hear (e.g. she...) as an agent (which would fit a continuation like ... greeted him), even when the sentence later requires the interpretation of a patient role (as in ... was greeted). We show that this processing principle is also operative in Hindi, a language where initial base-form noun phrases most commonly denote patients because many agents receive a special case marker ("ergative") and are often left out in discourse. This finding suggests that the principle is species wide and independent of the structural affordances of specific languages. As such, the principle favors the development and maintenance of case-marking systems that equate base-form cases with agents rather than with patients. We confirm this evolutionary bias by statistical analyses of phylogenetic signals in over 600 languages worldwide, controlling for confounding effects from language contact. Our findings suggest that at least one core property of grammar systematically adapts in its evolution to the neurophysiological conditions of the brain, independently of socio-historical factors. This opens up new avenues for understanding how specific properties of grammar have developed in tight interaction with the biological evolution of our species. PMID- 26267886 TI - Robustness and period sensitivity analysis of minimal models for biochemical oscillators. AB - Biological systems exhibit numerous oscillatory behaviors from calcium oscillations to circadian rhythms that recur daily. These autonomous oscillators contain complex feedbacks with nonlinear dynamics that enable spontaneous oscillations. The detailed nonlinear dynamics of such systems remains largely unknown. In this paper, we investigate robustness and dynamical differences of five minimal systems that may underlie fundamental molecular processes in biological oscillatory systems. Bifurcation analyses of these five models demonstrate an increase of oscillatory domains with a positive feedback mechanism that incorporates a reversible reaction, and dramatic changes in dynamics with small modifications in the wiring. Furthermore, our parameter sensitivity analysis and stochastic simulations reveal different rankings of hierarchy of period robustness that are determined by the number of sensitive parameters or network topology. In addition, systems with autocatalytic positive feedback loop are shown to be more robust than those with positive feedback via inhibitory degradation regardless of noise type. We demonstrate that robustness has to be comprehensively assessed with both parameter sensitivity analysis and stochastic simulations. PMID- 26267887 TI - L-Fucose-containing arabinogalactan-protein in radish leaves. AB - The carbohydrate moieties of arabinogalactan-proteins (AGPs) have beta-(1 -> 3) galactan backbones to which side chains of (1 -> 6)-linked beta-Gal residues are attached through O-6. Some of these side chains are further substituted with other sugars. We investigated the structure of L-Fuc-containing oligosaccharides released from the carbohydrate moieties of a radish leaf AGP by digestion with alpha-L-arabinofuranosidase, followed by exo-beta-(1 -> 3)-galactanase. We detected a series of neutral beta-(1 -> 6)-galactooligosaccharides branching variously at O-3 of the Gal residues, together with corresponding acidic derivatives terminating in 4-O-methyl-GlcA (4-Me-GlcA) or GlcA at the non reducing terminals. In neutral oligosaccharides with degree of polymerization (dp) mainly higher than 10, L-Fuc groups were attached through L-Ara residues as the sequence, alpha-L-Fucp-(1 -> 2)-alpha-L-Araf-(1 ->. This sequence was verified by isolation of the pentasaccharide alpha-L-Fuc-(1 -> 2)-alpha-L-Araf-(1 -> 3)-beta-Gal-(1 -> 6)-beta-Gal-(1 -> 6)-Gal upon digestion of the higher oligosaccharides with endo-beta-(1 -> 6)-galactanase. By contrast, in lower polymerized (predominantly dp 4) acidic oligosaccharides, L-Fuc groups were attached directly at the non-reducing terminals through alpha-(1 -> 2)-linkages, resulting in the release of the tetrasaccharides, alpha-L-Fucp-(1 -> 2)-beta-GlcA (1 -> 6)-beta-Gal-(1 -> 6)-Gal and alpha-L-Fucp-(1 -> 2)-beta-4-Me-GlcA-(1 -> 6) beta-Gal-(1 -> 6)-Gal. In long acidic oligosaccharides with dp mainly higher than 13, L-Fuc groups localized on branches were attached to the uronic acids directly and/or L-Ara residues as in the neutral oligosaccharides. PMID- 26267888 TI - Stereoselective synthesis and molecular modeling of chiral cyclopentanes. AB - The reaction of 3-methyseleno-2-methylselenomethyl-propene with benzyl 2,3 anhydro-4-O-triflyl-beta-L-ribopyranoside provides a major convenient enantiomeric product of 1-methylene-(benzyl3,4-dideoxy-alpha-D-arabinopyranoso) [3,4-c]-cyclopentane, with benzyl-2,3-anhydro-4-deoxy-4-C-(2-methyl- propen-3-yl) alpha-D-lyxopyranoside as a minor product. While the reaction of 3-methyseleno-2 [methylselenomethyl]-propene with benzyl 2,3-anhydro-4-O-triflyl-alpha-D ribopyranoside produces a good yield of benzyl-2,3-anhydro-4-deoxy-4-C-(2 methylpropen-3-yl)-alpha-D-lyxo-pyranoside. Molecular modeling and molecular dynamics simulations indicate that the intermediate in the reaction of the beta-L sugar frequently occupies an optimal conformation that leads to the formation of cyclopentane, while the intermediate in the reaction of the alpha-D sugar has a very small probability. The results point to the dominant role of the beta-L sugar intermediate in controlling the cyclopentane formation. PMID- 26267889 TI - Evaluation of different buffered peptone water (BPW) based enrichment broths for detection of Gram-negative foodborne pathogens from various food matrices. AB - This study evaluated the effects of changing the composition of the pre enrichment medium buffered peptone water (BPW) on the growth of stressed and unstressed Gram-negative foodborne pathogens in a one-broth enrichment strategy. BPW supplemented with an available iron source and sodium pyruvate, along with low levels of 8-hydroxyquinoline and sodium deoxycholate (BPW-S) improved the recovery of desiccated Cronobacter spp. from powdered infant formula. Growth of Salmonella and STEC was comparable in all BPW variants tested for different food matrices. In products with high levels of Gram-negative background flora (e.g. sprouts), the target organisms could not be reliably detected by PCR in any of the BPW variants tested unless the initial level exceeded 10(3) cfu/10 g of sprouts. Based on these results we suggest BPW-S for a one-broth enrichment strategy of stressed Gram-negative foodborne pathogens from dry products. However, a one-broth enrichment strategy based on BPW variants tested in this evaluation is not recommended for produce with a high level of Gram-negative background flora due to very high detection limits. PMID- 26267890 TI - Identification and quantification of the caproic acid-producing bacterium Clostridium kluyveri in the fermentation of pit mud used for Chinese strong-aroma type liquor production. AB - Chinese strong-aroma type liquor (CSAL) is a popular distilled alcoholic beverage in China. It is produced by a complex fermentation process that is conducted in pits in the ground. Ethyl caproate is a key flavor compound in CSAL and is thought to originate from caproic acid produced by Clostridia inhabiting the fermentation pit mud. However, the particular species of Clostridium associated with this production are poorly understood and problematic to quantify by culturing. In this study, a total of 28 closest relatives including 15 Clostridia and 8 Bacilli species in pit muds from three CSAL distilleries, were detected by culture-dependent and -independent methods. Among them, Clostridium kluyveri was identified as the main producer of caproic acid. One representative strain C. kluyveri N6 could produce caproic, butyric and octanoic acids and their corresponding ethyl esters, contributing significantly to CSAL flavor. A real time quantitative PCR assay of C. kluyveri in pit muds developed showed that a concentration of 1.79*10(7) 16S rRNA gene copies/g pit mud in LZ-old pit was approximately six times higher than that in HLM and YH pits and sixty times higher than that in LZ-new pit respectively. This method can be used to improve the management of pit mud microbiology and its impact on CSAL quality. PMID- 26267892 TI - Local Recurrence and Ocular Adnexal Complications Following Electronic Surface Brachytherapy for Basal Cell Carcinoma of the Lower Eyelid. AB - IMPORTANCE: Various treatment options exist for nonmelanoma skin cancer (NMSC), including topical agents, surgery, or definitive or adjuvant radiation therapy. Recently, electronic surface brachytherapy (ESB) has been described as a noninvasive option for NMSC. We report a case of local recurrence of basal cell carcinoma (BCC) and ocular complications following ESB to the lower eyelid. OBSERVATIONS: A man in his 60s presented with a recurrent BCC within the radiation field 10 months after undergoing ESB for a biopsy-proven BCC. In addition to the recurrence, he had contracture of the conjunctiva in the socket of his previously enucleated eye, as well as lower eyelid ectropion, resulting in displacement and loss of retention of his ocular prosthesis. CONCLUSIONS AND RELEVANCE: Electronic surface brachytherapy should be used with caution, particularly in the periocular region because the late effects of hypofractionated radiation may cause ocular and orbital complications. To our knowledge, this is the first reported case of ocular complications with this modality. This case highlights a local recurrence following use of this new treatment modality, suggesting further investigation is warranted to determine the safety and efficacy of ESB. PMID- 26267891 TI - The epidermal growth factor receptor (EGFR / HER-1) gatekeeper mutation T790M is present in European patients with early breast cancer. AB - The epidermal growth factor receptor (EGFR) is one of the major oncogenes identified in a variety of human malignancies including breast cancer (BC). EGFR mutations have been studied in lung cancer for some years and are established as important markers in guiding therapy with tyrosine kinase inhibitors (TKIs). In contrast, EGFR-mutations have been reported to be rare if not absent in human BC, although recent evidence has suggested a significant worldwide variation in somatic EGFR-mutations. Therefore, we investigated the presence of EGFR-mutations in 131 norwegian patients diagnosed with early breast cancer using real-time PCR methods. In the present study we identified three patients with an EGFR-T790M mutation. The PCR-findings were confirmed by direct Sanger sequencing. Two patients had triple-negative BC (TNBC) while the third was classified as luminal A subtype. The difference in incidence of T790M mutations comparing the TNBC subgroup with the other BC subgroups was statistical significant (P = 0.023). No other EGFR mutations were identified in the entire cohort. Interestingly, none of the patients had received any previous cancer treatment. To our best knowledge, the EGFR-T790M-TKI-resistance mutation has not been previously detected in breast cancer patients. Our findings contrast with the observations made in lung cancer patients where the EGFR-T790M-mutation is classified as a typical "second mutation"causing resistance to TKI-therapy during ongoing anticancer therapy. In conclusion, we have demonstrated for the first time that the EGFR-T790M-mutation occurs in primary human breast cancer patients. In the present study the EGFR T790M mutation was not accompanied by any simultaneous EGFR-activating mutation. PMID- 26267893 TI - [Extracorporeal membrane oxygenation in children]. AB - BACKGROUND: Children who require mechanical ventilation represent a high-risk population with significant morbidity and mortality. Experienced handling of conventional therapies including high frequency oscillation ventilation and initiation of newer treatment options such as surfactant or nitric oxide has led to some improvements. Nevertheless, extracorporeal membrane oxygenation (ECMO) is a life-saving technology in patients with respiratory failure refractory to maximal medical therapy. OBJECTIVE: This article shows the therapeutic management and the selection criteria for ECMO in neonates and children based on the clinical signs of acquired and congenital diseases that can lead to respiratory failure. RESULTS: The distribution of diagnoses, survival rates, and demographic change of ECMO in newborns since the beginning of documentation in 1986 by the Extracorporeal Life Support Organization (ELSO) registry and the largest German ECMO Center Mannheim are described. Despite a changed diagnostic distribution in the direction of congenital pulmonary disease, the survival rate of ECMO in the neonates has remained well above 70 %. In pediatric ECMO, the survival rate has also remained constant despite a more complex patient population. The highest values are seen in the youngest patients without underlying disease. CONCLUSION: Despite limited evidence and relatively few randomized trials in children, ECMO remains the safety net for patients with severe respiratory failure. Experience as measured by the annual number of cases plays an important role for the quality of results. PMID- 26267894 TI - Plasmodium falciparum Hop (PfHop) Interacts with the Hsp70 Chaperone in a Nucleotide-Dependent Fashion and Exhibits Ligand Selectivity. AB - Heat shock proteins (Hsps) play an important role in the development and pathogenicity of malaria parasites. One of the most prominent functions of Hsps is to facilitate the folding of other proteins. Hsps are thought to play a crucial role when malaria parasites invade their host cells and during their subsequent development in hepatocytes and red blood cells. It is thought that Hsps maintain proteostasis under the unfavourable conditions that malaria parasites encounter in the host environment. Although heat shock protein 70 (Hsp70) is capable of independent folding of some proteins, its functional cooperation with heat shock protein 90 (Hsp90) facilitates folding of some proteins such as kinases and steroid hormone receptors into their fully functional forms. The cooperation of Hsp70 and Hsp90 occurs through an adaptor protein called Hsp70-Hsp90 organising protein (Hop). We previously characterised the Hop protein from Plasmodium falciparum (PfHop). We observed that the protein co-localised with the cytosol-localised chaperones, PfHsp70-1 and PfHsp90 at the blood stages of the malaria parasite. In the current study, we demonstrated that PfHop is a stress-inducible protein. We further explored the direct interaction between PfHop and PfHsp70-1 using far Western and surface plasmon resonance (SPR) analyses. The interaction of the two proteins was further validated by co immunoprecipitation studies. We observed that PfHop and PfHsp70-1 associate in the absence and presence of either ATP or ADP. However, ADP appears to promote the association of the two proteins better than ATP. In addition, we investigated the specific interaction between PfHop TPR subdomains and PfHsp70-1/ PfHsp90, using a split-GFP approach. This method allowed us to observe that TPR1 and TPR2B subdomains of PfHop bind preferentially to the C-terminus of PfHsp70-1 compared to PfHsp90. Conversely, the TPR2A motif preferentially interacted with the C terminus of PfHsp90. Finally, we observed that recombinant PfHop occasionally eluted as a protein species of twice its predicted size, suggesting that it may occur as a dimer. We conducted SPR analysis which suggested that PfHop is capable of self-association in presence or absence of ATP/ADP. Overall, our findings suggest that PfHop is a stress-inducible protein that directly associates with PfHsp70-1 and PfHsp90. In addition, the protein is capable of self-association. The findings suggest that PfHop serves as a module that brings these two prominent chaperones (PfHsp70-1 and PfHsp90) into a functional complex. Since PfHsp70-1 and PfHsp90 are essential for parasite growth, findings from this study are important towards the development of possible antimalarial inhibitors targeting the cooperation of these two chaperones. PMID- 26267895 TI - DAPK1 Promoter Methylation and Cervical Cancer Risk: A Systematic Review and a Meta-Analysis. AB - OBJECTIVE: The Death-Associated Protein Kinase 1 (DAPK1) gene has been frequently investigated in cervical cancer (CC). The aim of the present study was to carry out a systematic review and a meta-analysis in order to evaluate DAPK1 promoter methylation as an epigenetic marker for CC risk. METHODS: A systematic literature search was carried out. The Cochrane software package Review Manager 5.2 was used. The fixed-effects or random-effects models, according to heterogeneity across studies, were used to calculate odds ratios (ORs) and 95% Confidence Intervals (CIs). Furthermore, subgroup analyses were conducted by histological type, assays used to evaluate DAPK1 promoter methylation, and control sample source. RESULTS: A total of 20 papers, published between 2001 and 2014, on 1929 samples, were included in the meta-analysis. DAPK1 promoter methylation was associated with an increased CC risk based on the random effects model (OR: 21.20; 95%CI = 11.14-40.35). Omitting the most heterogeneous study, the between study heterogeneity decreased and the association increased (OR: 24.13; 95% CI = 15.83-36.78). The association was also confirmed in all the subgroups analyses. CONCLUSIONS: A significant strong association between DAPK1 promoter methylation and CC was shown and confirmed independently by histological tumor type, method used to evaluate methylation and source of control samples. Methylation markers may have value in early detection of CC precursor lesions, provide added reassurances of safety for women who are candidates for less frequent screens, and predict outcomes of women infected with human papilloma virus. PMID- 26267896 TI - Regime shifts in the anthropocene: drivers, risks, and resilience. AB - Many ecosystems can experience regime shifts: surprising, large and persistent changes in the function and structure of ecosystems. Assessing whether continued global change will lead to further regime shifts, or has the potential to trigger cascading regime shifts has been a central question in global change policy. Addressing this issue has, however, been hampered by the focus of regime shift research on specific cases and types of regime shifts. To systematically assess the global risk of regime shifts we conducted a comparative analysis of 25 generic types of regime shifts across marine, terrestrial and polar systems; identifying their drivers, and impacts on ecosystem services. Our results show that the drivers of regime shifts are diverse and co-occur strongly, which suggests that continued global change can be expected to synchronously increase the risk of multiple regime shifts. Furthermore, many regime shift drivers are related to climate change and food production, whose links to the continued expansion of human activities makes them difficult to limit. Because many regime shifts can amplify the drivers of other regime shifts, continued global change can also be expected to increase the risk of cascading regime shifts. Nevertheless, the variety of scales at which regime shift drivers operate provides opportunities for reducing the risk of many types of regime shifts by addressing local or regional drivers, even in the absence of rapid reduction of global drivers. PMID- 26267897 TI - The role of aerobic fitness in cortical thickness and mathematics achievement in preadolescent children. AB - Growing evidence suggests that aerobic fitness benefits the brain and cognition during childhood. The present study is the first to explore cortical brain structure of higher fit and lower fit 9- and 10-year-old children, and how aerobic fitness and cortical thickness relate to academic achievement. We demonstrate that higher fit children (>70th percentile VO2max) showed decreased gray matter thickness in superior frontal cortex, superior temporal areas, and lateral occipital cortex, coupled with better mathematics achievement, compared to lower fit children (<30th percentile VO2max). Furthermore, cortical gray matter thinning in anterior and superior frontal areas was associated with superior arithmetic performance. Together, these data add to our knowledge of the biological markers of school achievement, particularly mathematics achievement, and raise the possibility that individual differences in aerobic fitness play an important role in cortical gray matter thinning during brain maturation. The establishment of predictors of academic performance is key to helping educators focus on interventions to maximize learning and success across the lifespan. PMID- 26267899 TI - Loss-of-Function PTPRD Mutations Lead to Increased STAT3 Activation and Sensitivity to STAT3 Inhibition in Head and Neck Cancer. AB - BACKGROUND: Protein tyrosine phosphatase receptor type D (PTPRD) is a putative tumor suppressor in several cancers including head and neck squamous cell carcinoma (HNSCC). STAT3 is a frequently hyperactivated oncogene in HNSCC. As STAT3 is a direct substrate of PTPRD, we sought to determine the genetic or epigenetic alterations of PTPRD that contribute to overactive STAT3 in HNSCC. METHODS: We analyzed data from The Cancer Genome Atlas (TCGA) and our previous whole-exome sequencing study and summarized the mutation, methylation, and copy number status of PTPRD in HNSCC and other cancers. In vitro studies involved standard transfection and MTT protocols, as well as methylation-specific PCR. RESULTS: Our findings indicate that PTPRD mutation, rather than methylation or copy number alteration, is the primary mechanism by which PTPRD function is lost in HNSCC. We demonstrate that overexpression of wild-type PTPRD in HNSCC cells significantly inhibits growth and STAT3 activation while PTPRD mutants do not, suggesting that mutation may lead to loss of function and subsequent hyper phosphorylation of PTPRD substrates, especially STAT3. Importantly, we determined that HNSCC cells harboring an endogenous PTPRD mutation are more sensitive to STAT3 blockade than PTPRD wild-type cells. We additionally found that PTPRD mRNA expression does not correlate with pSTAT3 expression, suggesting that alterations that manifest through altered mRNA expression, including hypermethylation and gene copy number alterations, do not significantly contribute to STAT3 overactivation in HNSCC. CONCLUSION: PTPRD mutation, but not methylation or copy number loss, may serve as a predictive biomarker of sensitivity to STAT3 inhibitors in HNSCC. PMID- 26267898 TI - Llama nanoantibodies with therapeutic potential against human norovirus diarrhea. AB - Noroviruses are a major cause of acute gastroenteritis, but no vaccines or therapeutic drugs are available. Llama-derived single chain antibody fragments (also called VHH) are small, recombinant monoclonal antibodies of 15 kDa with several advantages over conventional antibodies. The aim of this study was to generate recombinant monoclonal VHH specific for the two major norovirus (NoV) genogroups (GI and GII) in order to investigate their potential as immunotherapy for the treatment of NoV diarrhea. To accomplish this objective, two llamas were immunized with either GI.1 (Norwalk-1968) or GII.4 (MD2004) VLPs. After immunization, peripheral blood lymphocytes were collected and used to generate two VHH libraries. Using phage display technology, 10 VHH clones specific for GI.1, and 8 specific for GII.4 were selected for further characterization. All VHH recognized conformational epitopes in the P domain of the immunizing VP1 capsid protein, with the exception of one GII.4 VHH that recognized a linear P domain epitope. The GI.1 VHHs were highly specific for the immunizing GI.1 genotype, with only one VHH cross-reacting with GI.3 genotype. The GII.4 VHHs reacted with the immunizing GII.4 strain and showed a varying reactivity profile among different GII genotypes. One VHH specific for GI.1 and three specific for GII.4 could block the binding of homologous VLPs to synthetic HBGA carbohydrates, saliva, and pig gastric mucin, and in addition, could inhibit the hemagglutination of red blood cells by homologous VLPs. The ability of Nov specific VHHs to perform well in these surrogate neutralization assays supports their further development as immunotherapy for NoV treatment and immunoprophylaxis. PMID- 26267900 TI - An Innovative Pseudotypes-Based Enzyme-Linked Lectin Assay for the Measurement of Functional Anti-Neuraminidase Antibodies. AB - Antibodies (Ab) to neuraminidase (NA) play a role in limiting influenza infection and might help reduce the disease impact. The most widely used serological assay to measure functional anti-NA immune responses is the Enzyme-Linked Lectin Assay (ELLA) which relies on hemagglutinin (HA) mismatched virus reassortants, or detergent treated viruses as the NA source to overcome interference associated with steric hindrance of anti-HA Ab present in sera. The difficulty in producing and handling these reagents, which are not easily adapted for screening large numbers of samples, limits the routine analysis of functional anti-NA Ab in clinical trials. In this study, we produced influenza lentiviral pseudoparticles (PPs) containing only the NA antigen (NA-PPs) with a simple two-plasmid co transfection system. NA-PPs were characterized and tested as an innovative source of NA in the NA inhibition (NI) assay. Both swine A/California/07/2009 (H1N1) and avian A/turkey/Turkey/01/2005 (H5N1) N1s within NA-PPs retained their sialidase activity and were specifically inhibited by homologous and N1 subtype-specific, heterologous sheep sera. Moreover, A/California/07/2009 N1-PPs were a better source of NA compared to whole live and detergent treated H1N1 viruses in ELLA, likely due to lack of interference by anti-HA Ab, and absence of possible structural modifications caused by treatment with detergent. This innovative assay is safer and applicable to all NAs. Taken together, these results highlight the potential of NA-PPs-based NI assays to be developed as sensitive, flexible, easy to handle and scalable serological tests for routine NA immune response analysis. PMID- 26267901 TI - Oxygen Mapping within Healthy and Acutely Infarcted Brain Tissue in Humans Using the NMR Relaxation of Lipids: A Proof-Of-Concept Translational Study. AB - The clinical applicability of brain oxygenation mapping using the MOBILE (Mapping of Oxygen By Imaging Lipids relaxation Enhancement) magnetic resonance (MR) technique was assessed in the clinical setting of normal brain and of acute cerebral ischemia as a founding proof-of-concept translational study. Changes in the oxygenation level within healthy brain tissue can be detected by analyzing the spin-lattice proton relaxation ('Global T1' combining water and lipid protons) because of the paramagnetic properties of molecular oxygen. It was hypothesized that selective measurement of the relaxation of the lipid protons ('Lipids T1') would result in enhanced sensitivity of pO2 mapping because of higher solubility of oxygen in lipids than in water, and this was demonstrated in pre-clinical models using the MOBILE technique. In the present study, 12 healthy volunteers and eight patients with acute (48-72 hours) brain infarction were examined with the same clinical 3T MR system. Both Lipids R1 (R1 = 1/T1) and Global R1 were significantly different in the infarcted area and the contralateral unaffected brain tissue, with a higher statistical significance for Lipids R1 (median difference: 0.408 s-1; p<0.0001) than for Global R1 (median difference: 0.154 s-1; p = 0.027). Both Lipids R1 and Global R1 values in the unaffected contralateral brain tissue of stroke patients were not significantly different from the R1 values calculated in the brain tissue of healthy volunteers. The main limitations of the present prototypic version of the MOBILE sequence are the long acquisition time (4 min), hampering robustness of data in uncooperative patients, and a 2 mm slice thickness precluding accurate measurements in small infarcts because of partial volume averaging effects. PMID- 26267902 TI - Correction: Circulating miR-25-3p and miR-451a May Be Potential Biomarkers for the Diagnosis of Papillary Thyroid Carcinoma. PMID- 26267904 TI - The interaction of economic rewards and moral convictions in predicting attitudes toward resource use. AB - When people are morally convicted regarding a specific issue, these convictions exert a powerful influence on their attitudes and behavior. In the current research we examined whether there are boundary conditions to the influence of this effect. Specifically, whether in the context of salient economic rewards, moral convictions may become weaker predictors of attitudes regarding resource use. Focusing on the issue of mining we gathered large-scale samples across three different continents (Australia, Chile, and China). We found that moral convictions against mining were related to a reduced acceptance of mining in each country, while perceived economic rewards from mining increased acceptance. These two motivations interacted, however, such that when perceived economic benefit from mining was high, the influence of moral conviction was weaker. The results highlight the importance of understanding the roles of both moral conviction and financial gain in motivating attitudes towards resource use. PMID- 26267903 TI - beta-Hydroxy-beta-Methylbutyrate (HMB) Promotes Neurite Outgrowth in Neuro2a Cells. AB - beta-Hydroxy-beta-methylbutyrate (HMB) has been shown to enhance cell survival, differentiation and protein turnover in muscle, mainly activating phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinases/ extracellular-signal-regulated kinases (MAPK/ERK) signaling pathways. Since these two pathways are related to neuronal survival and differentiation, in this study, we have investigated the neurotrophic effects of HMB in mouse neuroblastoma Neuro2a cells. In Neuro2a cells, HMB promotes differentiation to neurites independent from any effects on proliferation. These effects are mediated by activation of both the PI3K/Akt and the extracellular signal-regulated kinases (ERK1/2) signaling as demonstrated by the use of specific inhibitors of these two pathways. As myocyte-enhancer factor 2 (MEF2) family of transcription factors are involved in neuronal survival and plasticity, the transcriptional activity and protein levels of MEF2 were also evaluated. HMB promoted MEF2-dependent transcriptional activity mediated by the activation of Akt and ERK1/2 pathways. Furthermore, HMB increases the expression of brain glucose transporters 1 (GLUT1) and 3 (GLUT3), and mTOR phosphorylation, which translates in a higher protein synthesis in Neuro2a cells. Furthermore, Torin1 and rapamycin effects on MEF2 transcriptional activity and HMB-dependent neurite outgrowth support that HMB acts through mTORC2. Together, these findings provide clear evidence to support an important role of HMB in neurite outgrowth. PMID- 26267905 TI - Practices of Dengue Fever Prevention and the Associated Factors among the Orang Asli in Peninsular Malaysia. AB - BACKGROUND: Dengue is prevalent among Malaysia's indigenous peoples, known as the Orang Asli, and it poses a serious health threat to them. The study aims to look at the socio-demographic factors, health beliefs, and knowledge about dengue and its association to dengue prevention practices among Orang Asli communities in Peninsular Malaysia. METHODS: A cross-sectional survey was conducted in 16 randomly selected Orang Asli villages from eight states in Peninsular Malaysia from April 2012 until February 2013. RESULTS: A total of 560 Orang Asli were interviewed and 505 completed the survey. Slightly above half of the participants (n = 280, 55.4%) had a total dengue prevention score of 51-100 (of a possible score of 0-100). Multivariate analysis findings showed dengue knowledge, perceived barriers to perform dengue prevention, fogging frequency, and perceived susceptibility to dengue fever as significant factors associated to dengue prevention practices. Participants with a lower dengue knowledge score (score 0 18) were less likely (OR = 0.63, 95%CI = 0.44-0.92 vs. score 19-36, P = 0.015) to practice dengue prevention. Participants with low perceived barriers to prevent dengue (score of 1-5) were more likely (OR = 2.06, 95%CI = 1.21-3.53, vs. score of 6-10, P = 0.008) to practice dengue prevention. Villages that were not fogged (OR = 0.49, 95%CI = 0.24-0.99, P = 0.045) or rarely fogged (OR = 0.40, 95%CI = 0.22-0.75, P = 0.004) had lower dengue prevention practices than villages that were fogged often. Participants with low perceived susceptibility of acquiring dengue (score of 1-5) were less likely (OR = 0.54, 95%CI = 0.33-0.89 vs. score of 6-10, P = 0.018) to practice dengue prevention measures. CONCLUSION: Findings imply that educational and health programmes should focus on enhancing dengue knowledge and perceived susceptibility of acquiring dengue and reducing perceived barriers to performing dengue prevention practices among the Orang Asli. More outreach on mosquito control campaigns should be carried out especially in villages where mosquito fogging is frequent. PMID- 26267906 TI - Binding of the Lactococcal Drug Dependent Transcriptional Regulator LmrR to Its Ligands and Responsive Promoter Regions. AB - The heterodimeric ABC transporter LmrCD from Lactococcus lactis is able to extrude several different toxic compounds from the cell, fulfilling a role in the intrinsic and induced drug resistance. The expression of the lmrCD genes is regulated by the multi-drug binding repressor LmrR, which also binds to its own promoter to autoregulate its own expression. Previously, we reported the crystal structure of LmrR in the presence and absence of the drugs Hoechst 33342 and daunomycin. Analysis of the mechanism how drugs control the repressor activity of LmrR is impeded by the fact that these drugs also bind to DNA. Here we identified, using X-ray crystallography and fluorescence, that riboflavin binds into the drug binding cavity of LmrR, adopting a similar binding mode as Hoechst 33342 and daunomycin. Microscale thermophoresis was employed to quantify the binding affinity of LmrR to its responsive promoter regions and to evaluate the cognate site of LmrR in the lmrCD promoter region. Riboflavin reduces the binding affinity of LmrR for the promoter regions. Our results support a model wherein drug binding to LmrR relieves the LmrR dependent repression of the lmrCD genes. PMID- 26267907 TI - Performance of Dutch children on the Bayley III: a comparison study of US and Dutch norms. AB - BACKGROUND: The Bayley Scales of Infant and Toddler Development-third edition (Bayley-III) are frequently used to assess early child development worldwide. However, the original standardization only included US children, and it is still unclear whether or not these norms are adequate for use in other populations. Recently, norms for the Dutch version of the Bayley-III (The Bayley-III-NL) were made. Scores based on Dutch and US norms were compared to study the need for population-specific norms. METHODS: Scaled scores based on Dutch and US norms were compared for 1912 children between 14 days and 42 months 14 days. Next, the proportions of children scoring < 1-SD and < -2 SD based on the two norms were compared, to identify over- or under-referral for developmental delay resulting from non-population-based norms. RESULTS: Scaled scores based on Dutch norms fluctuated around values based on US norms on all subtests. The extent of the deviations differed across ages and subtests. Differences in means were significant across all five subtests (p < .01) with small to large effect sizes (etap2) ranging from .03 to .26). Using the US instead of Dutch norms resulted in over-referral regarding gross motor skills, and under-referral regarding cognitive, receptive communication, expressive communication, and fine motor skills. CONCLUSIONS: The Dutch norms differ from the US norms for all subtests and these differences are clinically relevant. Population specific norms are needed to identify children with low scores for referral and intervention, and to facilitate international comparisons of population data. PMID- 26267908 TI - Impact of Corticosteroids on Mortality in Patients with Acute Respiratory Distress Syndrome: A Systematic Review and Meta-analysis. AB - OBJECTIVE: The impact of corticosteroids on acute respiratory distress syndrome (ARDS) mortality remains controversial following the publication of numerous trials, observational studies and meta-analyses. An updated meta-analysis is warranted, as a few original studies on this topic have been published since the last meta-analysis. METHODS: We searched for eligible articles using four databases. In particular, we included full-length original articles providing sufficient data for evaluating the impact of corticosteroid treatment on adult ARDS mortality in the form of odds ratios. A fixed model with the confidence interval method was used. An assessment of publication bias and sensitivity analyses were also conducted. RESULTS: We included 11 of 185 articles. The pooled odds ratio for corticosteroids with respect to all-cause mortality involving 949 patients was 0.77 [95% confidence interval (CI): 0.58-1.03, p=0.079] with strong heterogeneity(I2=70%, p<0.001). The results of the sensitivity analysis, Begg Kendall test (tau=0.53, p=0.024)and funnel plot consistently suggested the existence of strong publication bias. After six potentially unpublished cohorts were filled using Duval's trim and fill method, the pooled odds ratio shifted to 1.11 (95% CI0.86-1.44, p=0.427). In addition, the sensitivity analyses suggested that corticosteroid treatment has a different impact on mortality depending on the comorbidities and trigger events. CONCLUSION: We were unable to confirm, based on the data of published studies, the favorable impact of corticosteroid therapy on mortality in overall ARDS cases. Published articles exhibit strong publication bias,and previous meta-analyses may be affected by this publication bias. Further research focusing on pathophysiology- or trigger event-specific ARDS is anticipated. PMID- 26267910 TI - All of medicine's a stage. PMID- 26267909 TI - Pancreatic Insulinoma Misdiagnosed as Epilepsy for Eight Years: A Case Report and Literature Review. AB - A 58-year-old Chinese man presented with intermittent seizure episodes after being misdiagnosed with epilepsy for eight years. MRI revealed an abnormally strong signal in the distal pancreas. The patient was subsequently diagnosed with pancreatic insulinoma based on the histological findings, and his symptoms improved following surgical removal of the tumor. The appearance of unusual manifestations of insulinoma makes it difficult to diagnose the condition. This disorder should be included in the differential diagnosis of epilepsy and mental illness. PMID- 26267912 TI - Keeping patients under wraps. PMID- 26267911 TI - Prescription for dance. PMID- 26267913 TI - Instrumental care. PMID- 26267914 TI - Voice work. PMID- 26267915 TI - Three medical students on what prompted them to take up an artistic challenge. PMID- 26267916 TI - Task forces Task forces to examine health care financing, opioids, more. PMID- 26267917 TI - Prior authorization reform: We are just getting started. PMID- 26267918 TI - Mental Health Messaging to College Students. Three Arts-Based Approaches. PMID- 26267919 TI - Athlete's Dystonia. An Occupational Hazard of Athletes. PMID- 26267920 TI - Capsule Endoscopy and Left Ventricular Assist Devices. PMID- 26267921 TI - A Unique Left Ventricular Infiltrate Discovered in a 29-Year-Old, Causing Cardiac Arrest. PMID- 26267922 TI - Pseudohyperkalemia in Chronic Lymphocytic Leukemia. Longitudinal Analysis and Review of the Literature. PMID- 26267923 TI - Diffuse Large B Cell Lymphoma Presenting as Transverse Myelitis. PMID- 26267924 TI - Improvement in Left Ventricular Function Despite No Change in T2* with Iron Chelation in Secondary Hemochromatosis. PMID- 26267925 TI - Be Positive! PMID- 26267926 TI - Dissolving Decades. PMID- 26267927 TI - Alton Ochsner, MD and Tobacco. PMID- 26267928 TI - Cerebral Amyloid Angiopathy with Angiitis: Emerging Options for Treatment. AB - Two cases of cerebral amyloid angiopathy with features of angiitis are reported. The role of immunosuppressive therapy is reviewed. PMID- 26267929 TI - Case Report: Chorioamnionitis Attributed to Streptococcus thoraltensis. AB - Streptococcus thoraltensis is a recently described species, isolated from the intestinal and genital tracts of swine and from rabbit feces. We describe here a case of chorioamnionitis, with paternal swine exposure, potentially attributable to S. thoraltensis. To our knowledge, this is the first reported human infection by this organism. PMID- 26267930 TI - Postpartum Spontaneous Coronary Artery Dissection An Uncommon Cause of Acute Coronary Syndrome. AB - Spontaneous coronary artery dissection (SCAD) is an uncommon cause of acute coronary syndrome (ACS) that tends to affect young females. Diagnosis is confirmed by a dissection flap that is seen on coronary angiogram in the absence of underlying coronary atherosclerosis. New techniques in intra-coronary imaging such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) are useful in diagnosing SCAD. These techniques are helpful because SCAD is often associated with intra-mural hematoma within the vessel wall that would not be visualized on coronary angiography. Given the lack of randomized trials, most data on treatment of this relatively uncommon condition is controversial and based on expert opinion. Postpartum SCAD comprises a small subgroup of all patients presenting with SCAD. PMID- 26267931 TI - Comparison of Content and Format for Upper Respiratory Illness Antibiotic Prescribing Guideline Developed by Two Midwestern Organizations. AB - Antimicrobial resistance is a rapidly emerging public health problem, largely due to antibiotic prescribing which lacks an evidence base. We previously reported the results of local efforts within a single healthcare system at devising clinical guidelines to reduce unnecessary and even inappropriate antibiotic prescribing. This paper presents a comparison of the antibiotic guidelines developed by that process with those released by Institute for Clinical Systems Improvement, a national clinical quality organization. We found that the content of the guidelines are comparable, but not identical, while the formats differed, fitting separate but overlapping niches. PMID- 26267932 TI - Primary Care Follow-up of the NICU Graduate. PMID- 26267933 TI - Medicare Star Ratings: How Pharmacies Are Impacted and What That May Mean for Prescribers. PMID- 26267934 TI - Extenuating Circumstances: Smoking and Mental Illness: Closely Aligned Co Mordities. PMID- 26267936 TI - DAKOTACARE Update: Fatherhood, Revisited. PMID- 26267935 TI - Extenuating Circumstances: William Osler and Stonewall Jackson: The Rest of the Story. PMID- 26267937 TI - Quality Focus: Great Plains Quality Innovation Network/South Dakota is launching "Voices for Quality Healthcare" Advisory Board to Promote Patient and Family Engagement. PMID- 26267938 TI - Patient Education: Popping-Corn Rhythm. PMID- 26267939 TI - SDBMOE Board News. PMID- 26267941 TI - [Adapting analgesics prescription to the individual: precision medicine]. PMID- 26267942 TI - [Prescription of antidepressants in the treatment of pain: role of pharmacogenetics]. AB - Antidepressants, mainly tricyclic and non-selective reuptake inhibitors of serotonin antidepressants, are part of the treatment of chronic pain. The management is complicated by a large interindividual variability of efficacy and tolerance. Important part of this variability is associated with nucleotide polymorphisms of genes encoding enzymes involved in the pharmacokinetics and pharmacodynamics of these molecules. Identification of these genetic variants could to predict clinical consequences and allowed individualized adjustments in medication or dosage. This article presents the current knowledge on the influence of genetics on the efficacy and adverse effects of antidepressants used in chronic pain treatment. PMID- 26267943 TI - [Analgesia in patients with hepatic impairment]. AB - The lack of clear recommendations makes optimal pain management difficult in patients with hepatic function impairment. This article reviews the evidence on commonly used analgesics (paracetamol, NSAIDs, opiates). Paracetamol can be safely used at low doses (2-3 grams per day) for a period not exceeding a few days. NSAIDs should be avoided because of their direct hepatic toxicity and an increased risk of life-threatening side-effects (hemorrhagic, renal). Glucuronoconjugated opiates should be preferred but all must be used carefully because of the risk of side effects. Dosage reduction and/or increased dose interval are often required. PMID- 26267944 TI - [The use of transdermal opioids in patients in oncological remission suffering from chronic pain]. AB - Today, oncological patients in remission are becoming more numerous and about a third have chronic pain from various etiologies. In the objective of a comprehensive management plan for chronic pain in these patients, therapeutic goals, conditions and terms of prescription of opioids in the long-term should be discussed. The transdermal route may be an attractive alternative when analgesic treatment of moderate to severe pain is balanced. It provides increased comfort in selected patients in whom oral administration is difficult or a polypharmacy troublesome. Risks/benefits of a prescription of opioids in the treatment of chronic pain in patients in oncological remission should be re-evaluated and included in a multimodal support. PMID- 26267945 TI - [Clinical pharmacology of medical cannabinoids in chronic pain]. AB - In Switzerland, medical cannabinoids can be prescribed under compassionate use after special authorization in justified indications such as refractory pain. Evidence of efficacy in pain is limited and the clinical benefit seems to be modest. Their drug-drug interactions (DDI) profile is poorly documented. Cytochromes P450 (CYP) 2C9 and 3A4 are involved in the metabolism of tetrahydrocannabinol and cannabidiol, which implies possible DDI with CYP450 inhibitor and inducer, such as anticonvulsivants and HIV protease inhibitors, which may be prescribed in patients with neuropathic pain. PMID- 26267947 TI - [Chronic noncancer pain and patient education: a place for e-learning?]. AB - Chronic non cancerous pain considerably limits the patients' quality of life. Yet, chronic non cancerous pain has a prevalence as high as 25% to 35%, Therapeutic education allows to work on the knowledge and know-how about the disease, the treatment, the management of health resources and health behaviors. E-learning uses new technologies of communication to improve the quality of learning by facilitating access to the resources and favoring the interactivity. It is attractive by its wide accessibility and its limited logistic needs. The level of proof of its efficacy is weak, mainly because of methodological limitations. Some good quality studies are promising, with a positive effect of e learning programs on pain intensity, disability, autonomy and medication misuse. PMID- 26267946 TI - [Trauma and chronic pain: echoes and amplifications of physical and emotional suffering]. AB - Chronic pain often presents following a traumatic event, or alternatively, patients attribute pain to a trauma, whether this link is established or not. The psychological impact of trauma can significantly complicate the treatment of chronic pain. This article aims to review the known interactions between trauma and chronic pain. Following this review, it discusses therapeutic avenues suited to these complex situations, underlining the specific contributions of the different members of a multidisciplinary team. PMID- 26267948 TI - [Mindfulness in addiction therapy]. AB - Mindfulness based therapies are nowadays widely spread. During the last decades, several approches and specific programs have been scientifically challenged and developped. In the field of addictions the Mindfulness Based Relapse Prevention is the main reference program. Within this frame, mindfulness increases the awarness regarding triggers and automatic behavior related to drug abuse. It also has a favorable impact when dealing with craving. Currently, the scientific research has come to promissing conclusions as far as craving and relapse prediction are concerned. PMID- 26267949 TI - [Immunotherapy and cancers: last news from the front (Asco 2015)]. PMID- 26267950 TI - [Indignation: effect and responsibility at the crossroad between justice and injustice]. PMID- 26267951 TI - [Alcoholism and advertising: discover France and its wine-tasting tourism!]. PMID- 26267952 TI - [Renal colic management: an opportunity for simplification]. PMID- 26267953 TI - [2015, the psychiatry bible does not raise heated debates anymore]. PMID- 26267954 TI - [41% of Geneve residents are overweight]. PMID- 26267955 TI - [No mandatory participation for physicians in establishing electronic records]. PMID- 26267956 TI - [Dancing with artificial intelligence]. PMID- 26267957 TI - When Nurses Speak, Will the Nation Listen? PMID- 26267958 TI - The Value of Trust to Nursing. AB - Trust, one of nursing's intangible assets, impacts nurses' ability to form meaningful relationships with patients and this connection positively impacts health outcomes. Linking trust to the fabric of nursing and investing in its measurement will become essential to nursing's valuation and the resulting investment in nursing. Trust, as nursing's core value, should be fostered by nurse educators as they prepare the next generation of nurses. Nurse administrators should connect the trust a patient has for his or her nurse and patient cooperation and honest transparent communication between providers and the patient. Banking trust as a valuable nursing asset will substantiate nursing's marketing and support its worth. Nursing's trustworthiness is an intangible asset that warrants protection, as trust once lost is hard to recapture. PMID- 26267959 TI - The Rapid Growth of Graduates From Associate, Baccalaureate, And Graduate Programs in Nursing. AB - Growth in the number of RN graduates from 2002-2012 has been dramatic and broad based, occurring between both associate and baccalaureate programs, and has included people from all racial and eth- nic backgrounds. This growth has occurred in all types of public, private not-for- profit, and proprietary institu tions. The growth of RNs with gradu- ate degrees has also increased, particularly since 2004. Given the rapid production of nursing graduates, leaders in academic nursing education are urged to focus on the quality of nursing graduates, take steps to assure that graduates are well prepared for growth in nonhospital settings, ensure graduates are aware of the many challenges they will confront, and are well prepared to seize opportunities that will unfold during an era of health reform. PMID- 26267960 TI - The Hospital Work Environment And Job Satisfaction of Newly Licensed Registered Nurses. AB - In prior studies, newly licensed registered nurses (NLRNs) described their job as being stressful. Little is known about how the hospital work environment affects their job satisfaction. A random sample of NLRNs were surveyed to assess the influence of hospital work environment on job satisfaction. Perceptions of greater job difficulty, job demands, and patient load were significantly related to lower job satisfaction. In contrast, being White, working 12-hour shifts, working more hours, and having more job control, greater professional tenure, and a perception of a better initial orientation were significantly related to higher job satisfaction. PMID- 26267961 TI - Fostering Civility: An Interview With Cynthia Clark. PMID- 26267962 TI - e-Leadership: Leading in a Virtual Environment--Guiding Principles For Nurse Leaders. AB - Health care organizations have yet to appreciate the unique challenges associated with leading virtual teams. Nurse leaders are faced with managing some aspect of virtual teams that require a new way of leading. Nursing leadership will need to integrate and leverage technology to meet the growing demands of the health care industry. Guiding principles can help nurse leaders effectively guide their organizations in a virtual environment. It is important for e-leaders to create a social presence and build trusting relationships with all members of the virtual team. PMID- 26267963 TI - New BLS Data on Staff Nurse Compensation and Inflation-Adjusted Wages. AB - The wages of hospital staff RNs are a measure of the economic well-being of nurses across the board. The good news is the estimated average annual compensation for hospital RNs is now $107,307, consisting of $72,862 in wages and $34,445 in fringe benefits. The bad news is inflation has taken away virtually all of those increases. How long will it take the hospital industry to respond to the economic recovery, the decline of unemployment, and increased insurance coverage of the general population? Managing the transition will require greater attention to maintaining the equilibrium of hospital nurse wages. PMID- 26267964 TI - Dismantle or Improve ObamaCare? Nurses Must Take Action. AB - Following the 2014 mid-term elections, what will the next 2 years of Republican leadership do to change the structures still being put into place to meet the goals of the Affordable Care Act (ACA)? Nurses need to be visible by creating partnerships with their new state and federal representatives and by demonstrating collaboration through identified shared values. Nurses must hold all congressional leaders accountable for continuing to improve access to quality and affordable health care, while containing costs and strengthening incentives to provide a client-centered approach to care delivery. As health care reform legislation is a highly charged political battleground, nurses must support legislative changes in the ACA that will strengthen our health care system, not weaken it. PMID- 26267965 TI - Awakening the Human Heart: The Power of Poetry. PMID- 26267966 TI - Analytics for Better Care. PMID- 26267967 TI - Nursing Student Loan Debt: A Secondary Analysis of the National Student Nurses' Association Annual Survey of New Graduates. AB - The purpose of this study is to describe nursing student loan debt and financial choices from a secondary analysis of the National Student Nurses Association Annual New Graduate Survey. The findings in the secondary analysis show loan debt incurred by nursing students comparable to loan debt reported recently for all new college graduates in general. However, comparing types of programs and types of schools yielded clear variations. More than one-third of new graduates who reported having loans to repay were unemployed; more than one-quarter of those who worked part-time and one-quarter of those who worked full-time to finance their education were unemployed; and almost one-third of students whose parents had paid for their education were unemployed. New graduates from for-profit schools were more likely to report they had accumulated high debt to pay for school than all new graduates combined. Nursing students enter the job market with substantial financial debt that may impact their future. Educators and policymakers need to address these growing concerns to sustain a healthy supply of nurses. PMID- 26267968 TI - A Cost-Benefit Analysis: Electronic Clinical Procedural Resource Supporting Evidence-Based Practice. AB - There are many benefits of having an electronic reference at the patient bedside. Because of the significant costs involved, it is important to first understand if staff will utilize the system. A cost-benefit analysis of such an electronic clinical procedural resource at one large, academic health system showed a significant savings of $360,899. Having an electronic reference system at the patient bedside increased standardization throughout the organization. Additionally, clinical and instructional experts are not needed to write standard policies and procedures. Ongoing education was needed to increase utilization of the system within the organization. PMID- 26267969 TI - Evaluation of a Collaborative Care Model for Hospitalized Patients. AB - The current lack of collaborative care is contributing to higher mortality rates and longer hospital stays in the United States. A method for improving collaboration among health professionals for patients with congestive heart failure, the Clinical Integration Model (CIM), was implemented. The CIM utilized a process tool called the CareGraph to prioritize care for the interdisciplinary team. The CareGraph was used to focus communication and treatment strategies of health professionals on the patient rather than the discipline or specific task. Hospitals who used the collaborative model demonstrated shorter lengths of stay and cost per case. PMID- 26267970 TI - Bullying in the Nursing Workplace: Applying Evidence Using A Conceptual Framework. AB - Bullying in the nursing workplace can result in serious health-related outcomes for both nurses and patients who are under their care as well as the health care organizations. Bullying can erode the victim's professional competence and reputation and challenge the victim to maintain and improve professional identity. Although bullying can occur among co-workers, the most common form of bullying involves the abuse of power by superiors against subordinates. Persistent negative behaviors of a perpetrator indicates repeated negative behaviors of at least once or twice weekly by the perpetrator targeting the victim over period of time of at least 6 months and as long as 12 months. Building a conceptual framework of bullying specific to the nursing workplace is warranted to better understand bullying dynamics and its consequences while developing strategies to change the health care environment to a safer workplace for nurses. PMID- 26267971 TI - Nurse Credentials: What Is the Economic Value? AB - A workshop sponsored by the Institute of Medicine brought together health care leaders to focus on the impact of credentials on nurse, patient, and organization outcomes. Demonstrating the value of credentials is very challenging. Does the credential cause improvement? Or does it simply indicate which organizations are the better performers (and thus does not cause improvement)? As our health care system moves toward rewarding the value of health care, proponents of credentials will need to demonstrate credentials reflect true differences in the capacity to deliver health care. Credentialing is expensive; thus, it is imperative to critically assess the overall value of credentials, whether some credentials are more important than others, and how to support attainment of the most important credentials. PMID- 26267973 TI - A note from our editor. PMID- 26267972 TI - Nonprofit Charity Impacts Wounded Combat Veterans And Children Facing Adversity. AB - Mental and physical health challenges, especially for returning war veterans and their families, is a growing national concern. A grassroots program featuring equine therapy for these patients and their families shows promise in increasing self-esteem and self-confidence, reducing isolation and depression, and improving speaking and writing skills. PMID- 26267974 TI - RINSE AND RECOMMEND. PMID- 26267975 TI - KYM WHITE. PMID- 26267976 TI - Charting Change. Differentiating your brand from the inside out. PMID- 26267977 TI - The Patient/Treatment Cycle. How four marketing touch points can help improve patient outcomes. PMID- 26267978 TI - The New Loyalty Effect. PMID- 26267979 TI - Transplanting change. PMID- 26267980 TI - Healthy ambition. PMID- 26267981 TI - 10 Minutes With ANITA BRIKMAN. PMID- 26267982 TI - IMAGE HOMAGE. PMID- 26267983 TI - Naproxen for Pain Relief during Endometrial Biopsy: A Randomized Controlled Trial. AB - OBJECTIVE: To evaluate the effectiveness of naproxen 500 mg taken orally 30 minutes before, endometrial biopsy for pain relief during the procedure. MATERIAL AND METHOD: A double blind, randomized, placebo-controlled trial was conducted in 80 patients with indication for endometrial biopsy at Ramathibodi Hospital between April 2013 and January 2014. The patients were randomly allocated into two groups to receive naproxen 500 mg (n = 40) or placebo (n = 40), 30 minutes before endometrial biopsy. Pain score was assessed using Visual Analogue Scale during and 10 minutes after the procedure. Adverse events were observed. RESULTS: The mean pain score during endometrial biopsy in the treatment group was significantly lower compared to the placebo group (5.11 +/- 0.18 vs. 6.49 +/- 0.17, respectively, p-value < 0.001). However, the mean pain score at 10 minutes after endometrial sampling were minimal and had non-statistical significance in both groups. (0.60 +/- 0.56 vs. 0.59 +/- 0.64, p-value 0.971). CONCLUSION: Naproxen 500 mg taken orally 30 minutes before endometrial biopsy significantly reduce pain score during the procedure. PMID- 26267984 TI - Postoperative Pain Relief in Major Gynaecological Surgery by Perioperative Parecoxib Administration: Thammasat University Hospital Study. AB - OBJECTIVE: To study postoperative pain relief in major gynaecological surgery by perioperative parecoxib administration in Thammasat University Hospital. MATERIAL AND METHOD: This double-blind randomized controlled clinical trial was conducted in Thammasat University Hospital, Pathumthani, Thailand from October 2013 to May 2014. One hundred and twenty patients who underwent elective gynaecological surgery were randomized assigned to study and control groups. Study group (n = 60) received 40 mg parecoxib and control group (n = 60) received placebo at 1 hour before surgery. The postoperative visual analog scale (VAS) at 3, 6, 12 and 24 hours, frequency of meperidine consumption in 24 hours and side effects of parecoxib were recorded. RESULTS: VAS of study group after operation at 3, 6, 12 and 24 hours was significantly lower than control group. Meperidine consumption in placebo group was significantly higher than study group (27.50 +/- 19.36 and 48.75 +/- 28.15 mg, respectively; p < 0.001). There was no side effect from parecoxib in this study. CONCLUSION: Intravenous postoperativeparecoxib injection could relief pain and reduced meperidine consumption. Parecoxib could be safely used in gynaecological surgery for postoperative pain relief PMID- 26267985 TI - Efficacy of High vs. Conventional Ergocalciferol Dose for Increasing 25 Hydroxyvitamin D and Suppressing Parathyroid Hormone Levels in Stage III-IV CKD with Vitamin D Deficiency/Insufficiency: A Randomized Controlled Trial. AB - BACKGROUND: Vitamin D deficiency/insufficiency is common in chronic kidney disease (CKD) patients and it contributes to secondary hyperparathyroidism, which occurs early in CKD. It is not clear whether the Kidney Disease Outcomes Quality Initiative (K/DOQI) recommended doses of ergocalciferol are adequate for correction of vitamin D insufficiency and hyperparathyroidism. OBJECTIVE: To evaluate the parathyroid hormone (PTH)-lowering effect, safety, and tolerability of high-dose ergocalciferol compared with conventional-dose ergocalciferol in CKD subjects. MATERIAL AND METHOD: We enrolled CKD stage III-IV patients who had 25 hydroxyvitamin D (25-OH-D) level <30 ng/mL. The patients were randomized into two groups, control group treated with ergocalciferol as recommended by K/DOQI guidelines, and treatment group treated with double dosage of ergocalciferol from the recommendation. We compared serum 25-OH-D, intact-PTH, phosphate, calcium, and bone biomarker levels, during the 8-week intervention. RESULTS: Sixty-eight patients were included (34 controls and 34 treatments). Baseline characteristics of both groups were similar except calcium level 9.12 +/- 0.56 mg/dL in control group and 9.44 +/- 0.38 mg/dL in treatment group (p = 0.009), but not clinically significant. At the end of the 8-week, the mean 25-OH-D level significantly increased from 20.99 +/- 6.68 to 33.41 +/- 8.92 ng/mL in the treatment group (p = 0.001) and increased from 20.84 +/- 7.21 to 23.42 +/- 7.89 ng/mL in the control group (p = 0.026). There was also a significantly greater increase of 25-OH-D levels in the treatment group. Additionally, PTH levels significantly decreased from 90.75 +/- 67.12 to 76.40 +/- 45.97 at 8 weeks (p = 0.024) in the treatment group, and there was no change in the control group (97.14 +/- 83.52 vs. 101.13 +/- 95.03 pg/mL, p = 0.546). Serum calcium, phosphate, and adverse effects did not significantly change in either group throughout the study. CONCLUSION: In addition to improving vitamin D levels, oral high-dose ergocalciferol was safe and had a beneficial effect in decreasing PTH in patients with stage III-IV of CKD. PMID- 26267986 TI - Risk Factors of Stroke in Pathumthani Province, Thailand. AB - OBJECTIVE: To study risk factors of stroke in Pathumthani. MATERIAL AND METHOD: Pathumthani comprises of seven districts. One sub-district was selected from each district. The subject group was those aged 30 years or older Staffs of Sub District Health Promotion Hospitals were trained to assist in the data gathering based on questionnaires on blood sugar and lipid levels. The staffs conduct cross sectional analyses of the information. RESULTS: Of 714 subjects, most were female (66.9%). The average age was 56 years (SD 10.7). Forty-six point two percent had their body mass index of 25 kg/m2 or more. Fifty-six point four percent had larger waist circumference than average. Sixty point eight percent had their cholesterol levels over 200 mg/dl while 14.9% had their blood sugar levels of 126 mg/dl or higher Seven subjects (1.0%) had stroke. As for the risk factors, 32.4% had hypertension; 16.9% had hyperlipidemia; 13.1% had diabetes mellitus; 8.9% smoked and 2.0% had heart diseases. Forty-eight point seven percent had at least one risk factor, among these, 55.2%, 29.9%, 12.0%, 2.9% and 0.0% had one, two, three, four andfive factors, respectively. CONCLUSION: The prevalence rate of stroke in Pathumthani was one in 100 people aged 30 years or older. The observed important risk factor of stroke was hypertension. Nearly half of the subjects had at least one risk factor Suggested ways in changing the behaviors are the control of the disease, the diets and the increasing physical exercise. PMID- 26267987 TI - Time Duration of Oxygen Adaptation Immediately after Birth; Monitoring by Pulse Oximeter in Perinatal Period of the Infants at Charoenkrung Pracharak Hospital. AB - BACKGROUND: Oxygen Saturation is one of the important data to determine patient status and worldwide applied in several situations. Evaluation about status of immediate perinatal period of the infant usually uses clinical assessment, Apgar scoring, which had been used for a long time without other scientific measurement. Pulse oximeter the non-invasive measurement of oxygen saturation, may play role for oxygen saturation evaluation in newborn that immediately change from intra to extra uterine environment. OBJECTIVE: Monitoring the time duration that immediately born infants by normal labor or Cesarean section modes, used to archived target oxygen saturation (SpO) and looking for the other factors that influence oxygen saturation adaptation. MATERIAL AND METHOD: The data of the 553 infants born in Charoenkrung Pracharak Hospital, Bangkok, Thailand between October 2012 and April 2013 were collected. The 204 healthy newborns that met all criteria were studied. All infants were recorded pulse oximeter from the second to the tenth minute after birth. They were grouped by several factors such as maternal gravidity, gestational age, mode of delivery, Apgar score, birth weight, and sex. Time interval to achieve target oxygen saturation (SpO2 >= 90%) was collected for analysis. RESULTS: The oxygen saturation of infants immediately after birth showed an increase. Median time interval was 6.5 (2-10) minutes for 90% saturation and 7 (2-10) minutes for 95% saturation, respectively. Only mode of delivery showed statistical significant time difference (p < 0.001). A Cox proportional hazards analysis of the Kaplan-Meier curves demonstrated that infants born by cesarean delivery took significantly longer time to reach a stable SpO2 >= 90% than infants born by vaginal delivery (95% CI = 1.28 to 2.74; p < 0.01). CONCLUSION: A newly born infant has to take 6.5 minutes (2-10) after birth to adjust their oxygen saturation to reach normal higher level of extra uterine life, median SpO2 of 90%. Furthermore, mode of delivery makes a significant difference of oxygen saturation status; the cesarean route takes significantly longer time than the vaginal route to achieve SpO2 >= 90%. PMID- 26267988 TI - Descriptive Profile Outcomes between Closed and Open Drainage Systems Following Urethroplasty. AB - BACKGROUND: An indwelling urinary catheter or urethral stent are standardly used following a urethroplasty to prevent post-operative urinary retention. There are both closed drainage system (CDS) and open drainage system (ODS) available. OBJECTIVE: The study was designed to determine the outcomes between post operative CDS and ODS. MATERIAL AND METHOD: Fifty-seven hypospadias patients with 66 urethroplasties, performed by a single surgeon, were assessed. During the 40 month study period, the operative outcomes relative to the technique of both urinary catheter drainage systems were evaluated for length of hospital stay (LOS), cost of hospitalization, and post-operative complications. RESULTS: CDS and ODS drainage systems were performed in 32 and 34 operations, respectively. The patient characteristics, the surgical profiles, and post-operative complications were not statistically significant. The CDS/ODS group had median LOS (range) of 9 (1 to 22) 12 (1 to 6) days, respectively, and cost of hospitalization (SD) of 22,908 (4,455)/18,408 (3,848) Bahts respectively. Both had statistical significance, p < 0.001. The subgroup of 26 posterior hypospadias and TIP urethroplasties were also evaluated. CONCLUSION: Patients with hypospadias given an open drainage system after urethroplasty have a higher rate of early discharge, lower cost of hospitalization, and a lower rate of wound infection. PMID- 26267989 TI - Diagnosis and Treatment of Acute Mesenteric Ischemia: Clinical Analysis for 40 Cases of the Patients. AB - OBJECTIVE: To explore the methods of diagnosis and treatment of the patients with acute mesenteric ischemia (AMI). MATERIAL AND METHOD: The present study took place at Department of General Surgery, Xiangyang Central Hospital of Hubei Province, China between January 2002 and December 2013. The clinical data of 40 cases of AMI were analyzed. RESULTS: Among 40 cases of AMI, 38 had to surgical treatment and two had thrombolysis in superior mesenteric artery (SMA) through interventional radiology. Twenty cases died; thus, overall mortality was 50%. Fifteen cases were subjected to surgical or interventional therapy within 16 hours after onset, and all of them survived. Twenty-five cases were subjected to surgical treatments over 16 hours after onset andfive survived. There was significant difference between them (t = 3.4, p = 0.0009). CONCLUSION: The key point to improve survival rate of AMI was early diagnosis and treatment. In the process of treatment, more attention should be paid on recovering blood supply of SMA, and the relationship between total excision of necrotic intestine and reservation offunctional intestine. The operation should be handled properly to reduce the possibility of short bowel syndrome. PMID- 26267990 TI - Risk Assessment of Abdominal Wall Thickness Measured on Pre-Operative Computerized Tomography for Incisional Surgical Site Infection after Abdominal Surgery. AB - BACKGROUND: The surgical site infection (SSI) is a common complication of abdominal operation. It relates to increased hospital stay, increased healthcare cost, and decreased patient's quality of life. Obesity, usually defined by BMI, is known as one of the risks of SSI. However, the thickness of subcutaneous layers of abdominal wall might be an important local factor affecting the rate of SSI after the abdominal operations. OBJECTIVE: The objective of this study is to assess the importance of the abdominal wall thickness on incisional SSI rate. MATERIAL AND METHOD: The subjects of the present study were patients who had undergone major abdominal operations at Thammasat University Hospital between June 2013 and May 2014, and had been investigated with CT scans before their operations. The demographic data and clinical information of these patients were recorded. The thickness ofsubcutaneous fatty tissue from skin down to the most superficial layer of abdominal wall muscle at the surgical site was measured on CT images. The wound infectious complication was reviewed and categorized as superficial and deep incisional SSIfollowing the definition from Centersfor Disease Control and Prevention (CDC) guidelines. The significance ofeach potentialfactors on SSI rates was determined separately with student t-test for quantitative data and chi2-test for categorical data. Then all factors, which had p < 0.10, were included into the multivariate logistic regression analysis and were analyzed with significance at p < 0.05. RESULTS: One hundred and thirty-nine patients were included in this study. They all underwent major abdominal surgery and had had pre-operative CTscans. Post-operative SSI was 25.2% (35/139), superficial and deep types in 27 and 8 patients, respectively. The comparison of abdominal wall thickness between patients with and without infection was significantly different (20.0 +/- 8.4 mm and 16.0 +/- 7.2 mm, respectively). When the thickness at 20 mm was used as the cut-off value, 43 of 139 patients had abdominal wall thickness >= 20 mm. The incidence of SSI of the thickness +/-20 mm group was 37.2% (16/43) and of the less thickness group was 19.8% (19/96), with p < 0.05. The univariate analysis revealed that abdominal wall thickness >= 20 mm, body weight >= 60 kg, and wound classification were the important factors related to SSI after the abdominal operation. However, only abdominal wall thickness and wound classification were still significant by multivariate analysis. CONCLUSION: The findings of this study confirmed the significance of the subcutaneous thickness of abdominal wall at the surgical site on the incidence of incisional SSI. The thickness >= 20 mm had an effect on increasing post operative SSI rate especially in contaminated operations. These findings could be helpful in making healthcare providers fully aware and thus exercise special attention in wound care or even develop new modalities to prevent SSI in patients with the aforementioned risks. PMID- 26267991 TI - A Comparison of Pain Scales in Patients with Disorders of Consciousness Following Craniotomy. AB - OBJECTIVE: Evaluate the validity, reliability, and practicality of pain assessment tools in patients with disorders of consciousness who underwent craniotomy. MATERIAL AND METHOD: This prospective observational study cross validated three pain scales, FLACC (Face, Legs, Activity, Cry, Consolability), rFLACC (Revised FLA CC), and NCS (Nociception Coma Scale), based on validity, reliability, and practicality. After translation, the three pain scales were tested for concurrent validity, construct validity, and interrater reliability in patients who experienced disorders of consciousness within 24 hours following craniotomy. Opinions regarding practicality were elicited via questionnaire from nurses who have used and are familiar with these pain scales. RESULTS: Fifty eight patients were enrolled in the present study. Concurrent validity was supported by positive correlations among all scales, which ranged from r = 0.638 to r = 0.978. All scales yielded fair to moderate agreement (K = 0.380-0.626) with routine clinical decision to treat postoperative pain. Concurrent validity was much improved in the assessment of intubated patients. Construct validity was demonstrated by high scores (3-5) in higher pain situations before analgesic was given and low pain scores (0) in pain-free situations after analgesic was given. All scales had good interrater reliability (intraclass correlation = 0.7506 0.8810). CONCLUSION: All pain scales were found to be valid and reliable, especially in intubated patients. In terms ofpracticality, NCS was found to be the most acceptable by practitioners. PMID- 26267992 TI - Correlation between Retinal Nerve Fiber Layer Thickness and Central Corneal Thickness in Healthy Subjects. AB - OBJECTIVE: To evaluate the correlation between retinal nerve fiber layer (RNFL) thickness obtained by optical coherence tomography (Spectralis OCT Heidelberg Engineering, Heidelberg, Germany) and central corneal thickness (CCT) in healthy subjects. MATERIAL AND METHOD: This was a retrospective cross-sectional study. Two hundred twenty nine healthy subjects were included in the present study. All subjects received a standard ocular examination, including RNFL thickness measurement by optical coherence tomography. CCT measurement was performed by ultrasonic pachymeter. The Pearson's correlation test was used to determine the relationship between CCTandRNFL thickness. RESULTS: The significantly positive relationship was found between CCTand RNFL thickness in overall average and inferior sector. There was no statistically significant relationship found between CCT and the other sectors of RNFL thickness. CONCLUSION: CCT was statistically significant related to RNFL thickness in overall average and inferior sector in healthy subjects. PMID- 26267993 TI - Application of Gelatin-Coated Magnetic Particles for Isolation of Genomic DNA from Bones. AB - OBJECTIVE: To develop a method for human genomic DNA extraction from bone using gelatin-coated magnetic particles. MATERIAL AND METHOD: Thirty human metacarpal with the bone age ranging from 36 to 93 years were included in the present study. Genomic DNA was extracted from bones using gelatin-coated magnetic particles. The concentration and purity of DNA were analyzed in comparison with a reference method. In addition, the quality of extracted DNA was examined for sex determination by conventional polymerase chain reaction (PCR). RESULTS: The average DNA concentration using gelatin coated magnetic particles exhibited approximately 15 times higher than a reference method with an insignificantly difference of the DNA purity in both methods. Twelve (40%) and fifteen (50%) samples out of thirty DNA isolated using established and reference method, respectively, could be amplified and sex correctly determined by PCR. CONCLUSION: Gelatin coated magnetic particle is rapid, simple, and well-suited for isolation of DNA from bones. PMID- 26267994 TI - Intravenous Heroin-Associated Delayed Spongiform Leukoencephalopathy: Case Report and Reviews of the Literature. AB - Heroin-associated spongiform leukoencephalopathy is a rare, and sometimes fatal, condition usually caused by vapor inhalation of heroin. The authors report a 41 year-old man who was diagnosed with delayed spongiform leukoencephalopathy three weeks after injecting heroin intravenously. He had been admitted to another hospital due to acute heroin overdose, which had occurred four hours after intravenous injection of an unknown amount of heroin. His clinical condition showed progressive improvement and he was discharged 12 days after admission. Three weeks after this episode, his cognitive functioning declined. Akinetic mutism, spasticity and hyperreflexia of all extremities were observed. Electroencephalography (EEG) and imaging of the brain showed typical characteristics of spongiform leukoencephalopathy. The three and six-month follow up of the patient showed clinical improvement and this was corroborated through EEG measures and brain imaging. The discussion summarizes eight previously reported cases of intravenous heroin associated spongiform leukoencephalopathy and compares them to the authors'case. PMID- 26267995 TI - Induced Hypothermia in a Penetrating Trauma Patient with Cardiac Arrest from Exsanguination: The First Case Report. AB - The authors report the use of induced hypothermia in a stab wound patient with left common femoral artery injury who had cardiac arrest from exsanguination immediately after arriving at a private hospital. The patient was transferred to the authors' institution (a university hospital) after successful cardiopulmonary resuscitation, for vascular repair. The patient remained comatose five hours after the vascular repair. The induced hypothermia (target body temperature of 33 degrees C) was initiated 10 hours post arrest after the bleeding control and physiologic derangement restoration had been achieved. The patient recovered uneventfully with good neurological outcome. PMID- 26267996 TI - Left Paraduodenal Hernia As a Rare Cause of Small Bowel Obstruction in Elderly: A Case Report and Review of Literature. AB - The authors presented a case of left paraduodenal hernia as a cause of closed loop small bowel obstruction in an elderly patient. Internal hernias are a rare cause of intestinal obstruction. Paraduodenal hernias are the most frequent especially left sided, which are believed to be the result of malrotation of the midgut during embryonic period. The clinical presentations varied, ranging from asymptomatic, chronic abdominal pain, or acute abdominal pain as acute abdomen. Most of the patients usually have early presentation in adult life with average age of 38.5 years at time of diagnosis. Late presentation in elderly patient (> 70 years) is very rare due to its congenital in origin. This clinical entity is a diagnostic challenge, which happened in our case. When the diagnosis is late, the complication develops and may contribute to afatal outcome if left untreated Herein, the authors reported our case of left paraduodenal hernia with late presentation at age of 80, and reviewed literature. PMID- 26267997 TI - Ocular Malformations with Presumable Intraocular Calcification. AB - This is a case of ocular malformations with presumable intraocular calcification based on computed tomography (CT) imaging, magnetic resonance imaging (MRI) and ocular ultrasound (US) findings. The authors presented the clinical, imaging and pathological findings of this case. Intraocular calcification is the most important finding in retinoblastoma, which requires aggressive management. It is important to distinguish it from other intraocular lesions, especially intraocular calcified hematoma. PMID- 26268000 TI - Vaccination and Fluoridation. PMID- 26268001 TI - MDA Board Focuses on Strategic Planning, Membership Growth. PMID- 26268002 TI - State Dental Boards Are Not Immune from Antitrust Liability. PMID- 26268003 TI - This Will Only Hurt for a Minute.... PMID- 26268004 TI - Is It Ethical to Advertise Claims of Superiority? PMID- 26268005 TI - How the MDA Is Working Proactively to Preserve Community Water Fluoridation in Michigan. AB - Community water fluoridation has famously been called "one of the top 10 public health advances of the 20th century." Its record of success in dental health is unsurpassed. And yet now, in the 21st century, were seeing renewed anti-fluoride activity across the country and right here in our local communities. The MDA is stepping up to the challenge with a new, proactive campaign to ensure that Michigan citizens continue to enjoy fluoridation's benefits. PMID- 26268006 TI - Setting the Record Straight on Fluoride. PMID- 26268007 TI - "It Was Almost a Guerilla-Style Attack". How Boyne City Lost Fluoridation--And Got It Back. AB - The "antis" tried to get rid of fluoride in Boyne City. In fact, they succeeded- and fluoride was removed from the water supply. But thanks to concerned local citizens and dentists, the voters had a chance to decide the issue once and for all. Now, fluoride's back. PMID- 26268008 TI - MDA Dentists Help Lead the Fluoride Fight in Communities Statewide. PMID- 26268009 TI - The Significance of Ecstasy Use to Dental Practice. AB - Methylenedioxymethampetamine (MDMA), commonly known as ecstasy, is an illicit drug used by individuals seeking mood enhancement. Ecstasy's pharmacology, systemic, oral and dental manifestations are presented. Use of this drug is not limited to a particular socioeconomic class and, as such, all practicing dentists must be aware of both the intraoral effects of this drug and any possible alterations to dental treatment that might become necessary. Dental manifestations include bruxism, increased incidence of caries, xerostomia and oral ulcers. PMID- 26268010 TI - Replacement of Maxillary Permanent Central Incisors Lost Due to Trauma in the Mixed-Dentition. AB - Traumatic injuries to anterior teeth in children range from minor chipping to total tooth loss and occur more often in boys than in girls. The treatment of permanent tooth loss in younger patients is complicated by the difficulty of doing restorative procedures which may be influenced by pulpal size, clinical crown height, and a dental profile that is constantly changing. This case report presented a situation involving a 9-year-old boy who had experienced traumatic loss of the maxillary central incisors. Innovative materials coupled with sound principles of removable partial denture design were utilized to fabricate a cast metal removable denture prosthesis to satisfy the esthetic, functional and psychological dental needs of the patient and his parents. PMID- 26268011 TI - Life Insurance Needs Vary During Each of Your Life Stages. PMID- 26268013 TI - Breathing easy during building projects. AB - In an article that first appeared in Canadian Healthcare Facilities, Peter Semchuk, a senior associate with IBI Group, explains how an innovative approach was taken to optimising indoor air quality and infection control during the construction of the recently completed Fort Saskatchewan and Strathcona Community Hospital in Canada. PMID- 26268014 TI - Comfort, sustainability, and workflow improved. AB - Brett Seeney, BEng Hons, CEng, FIHEEM, MCIBSE, an associate at WSP in Melbourne reports, in an article first published in the IFHE Digest 2014, on a major redevelopment scheme at the Echuca Regional Health Hospital in Australia's northern Victoria. The project innovatively harnessed the latest building services engineering technology to help the hospital operate more in a more sustainable and efficient way, while simultaneously improving comfort for patients, visitors, and staff. PMID- 26268015 TI - Shouldering the load, maximising value. AB - In mid-November last year Ryhurst signed what it dubbed 'a ground-breaking strategic estates partnership' agreement with the Isle of Wight NHS Trust (HEJ - January 2015). Under the Wight Life Partnership, the two organisations will work in partnership 'to comprehensively review the estate across all the Trust's sites to ensure that buildings and grounds are being fully utilised, and suitable for modern healthcare'. This is Ryhurst's third such 'whole estate' joint-venture agreement with the NHS, and the first with a non-Foundation Trust, harnessing an approach that sees the company shoulder a considerable part of the burden of making optimum use of, and deriving 'maximum value' from, large healthcare estates. HEJ editor, Jonathan Baillie, reports. PMID- 26268016 TI - Low energy--bridging the Great Divide. AB - Professor Mathew Bacon, MD of The Conclude Consultancy, argues that with healthcare facilities required to play a considerable part in helping the UK meet tough carbon reduction targets, a new approach to designing large acute hospitals is required that takes significantly greater account of such facilities' 'In-use' energy consumption. Equally, he believes, designing hospitals that meet lower carbon consumption goals requires greater dialogue between clinicians and engineers so that the resulting clearer perspective on clinical processes can be leveraged to inform the engineering design, and achieve 'a close coupling' between the engineering design strategy and the working practice needs of users. PMID- 26268017 TI - Trust and British Gas partner in EPC scheme. AB - In late August last year the St George's Healthcare NHS Trust in south-west London signed what the Trust's Estates and Facilities team described as 'a historic partnership' with British Gas for a L12 m Energy Performance Contract energy reduction scheme--via which the energy company has guaranteed to deliver L1.1 m in annual savings over the next 15 years. The agreement will see British Gas replace four 35-year-old gas-powered steam boilers and an ageing CHP plant in the boiler house at the Trust's main acute facility, the StGeorge's Hospital in Tooting, and upgrade some of the associated infrastructure. British Gas will also maintain the new plant to ensure that the projected savings are achieved while the Trust owns the new assets. The Trust should gain financially--via lower energy costs and carbon emissions, while estates personnel will be better able to complete the many other estate maintenance issues that would otherwise be contracted out at one of London's biggest acute hospitals. PMID- 26268018 TI - Keeping costs down and revenue up. AB - Mike Hilditch, managing director of auctioneers, Hilditch Group, which has extensive experience in selling equipment on behalf of the NHS, advises, via a seven-step guide, on some of the key elements for estates and facilities teams to consider to ensure that site clearances both go to plan and reap maximum financial reward, including safeguarding potentially valuable 'kit' against opportunist thieves, and preventing confidential paperwork falling into the wrong hands. PMID- 26268019 TI - Four decades of change and evolution examined. AB - Phil Wade, director of Marketing at Static Systems Group, looks back at how bedhead services and trunking have developed over the past 40 years. Their development has, he says, been driven not only by increasingly stringent infection control criteria, the need for more attractive aesthetics, increased functionality, evolving communications technology, and the ability to adapt to meet changing needs, but equally by the growing part that clinicians and healthcare planners now play in the decision-making process for bedside layouts. He also looks forward to what we might expect to see in the future. PMID- 26268020 TI - Ebola preparedness priorities explained. AB - With the recent Ebola outbreak in West Africa widely considered the worst to date, and British nurse, Pauline Cafferkey, who was diagnosed with the virus in December after returning from work in Sierra Leone, recently discharged after being cared for in a special isolation unit at London's Royal Free Hospital, Jon Otter, scientific director of the Healthcare Division at Bioquell, considers prevention and control strategy for a disease which, by early January this year, had killed well over 8,000 people since the original outbreak just a year before. PMID- 26268021 TI - ISO 55000: Creating an asset management system. AB - In the October 2014 issue of HEJ, Keith Hamer, group vice-president, Asset Management & Engineering at Sodexo, and marketing director at Asset Wisdom, Kevin Main, argued that the new ISO 55000 standards present facilities managers with an opportunity to create 'a joined-up, whole lifecycle approach' to managing and delivering value from assets. In this article, Kevin Main and Chris Bradley, who runs various asset management projects, examine the process of creating an asset management system. PMID- 26268022 TI - Professional knowledge, ethical conduct. PMID- 26268023 TI - Small investments, huge savings. AB - Writing on behalf of the Building & Engineering Services Association (B&ES), Ewen Rose, an experienced journalist specialising in building engineering services, reports on a number of presentations at October's IHEEM Healthcare Estates 2014 conference where the focus was very much on how healthcare estates and facilities and healthcare engineering teams can save energy and cut carbon emissions through more efficient monitoring, and, if necessary, subsequent adjustment, of key HVAC plant. Among the key conclusions were that basic energy efficiency measures could 'shave millions of pounds from NHS estates' running costs', and that hospitals and other healthcare buildings face both 'an air-conditioning legal crisis', and a growing threat from outdoor air pollution. PMID- 26268024 TI - Ensuring that fire doors are fit for purpose. AB - Neil Ashdown, general manager of the Fire Door lnspecion Scheme (FDIS), considers the key steps for ensuring that fire doors are correctly specified, installed, maintained, inspected, and, when necessary, repaired, to enable them to effectively fulfil their role. PMID- 26268025 TI - Bringing a military approach to teaching. AB - Despite having only established the company nine years ago, the founders of Kidderminster-based Avensys Medical believe the company now offers not only one of the UK's most comprehensive maintenance, repair, consultancy, and equipment audit services for medical and dental equipment, but also one of the most tailored training portfolios for electro-biomedical (EBME) engineers working in healthcare settings to enable them to get the best out of such equipment, improve patient safety, optimise service life, and save both the NHS and private sector money. As HEJ editor, Jonathan Baillie, discovered on meeting one of the two co founders, ex-Royal Electrical and Mechanical Engineers (REME) artificer sergeant major (ASM) and MoD engineering trainer, Robert Strange, many of the company's key trainers have a strong military background, and it is the rigorous and disciplined approach this enables them to bring to their training that he believes singles the company out. PMID- 26268026 TI - Scottish experience can inform others. AB - With the Waste (Scotland) Regulations 2012, which actually came into effect on 1 January 2014 in Scotland, requiring all the country's healthcare facilities to separate their waste for recycling, waste management consultants, Jess Twemlow and Dr Adam Read of Ricardo-AEA, consider what healthcare facilities south of the border can learn from Scotland's experience about improved waste management and resource efficiency. PMID- 26268027 TI - Patient experience key in hospice refurb. AB - A major design and build scheme which has seen the inpatient unit at St. Luke's Hospice in Sheffield extended and refurbished to provide a more comfortable and homely environment, and bring the facilities up to the best 21st century standards, has benefited significantly from both high quality architecture and stakeholder commitment. The result, reports Matt Beach, associate at scheme architects, Race Cottam Associates, is an even better and 'more personal'environment for delivery of end-of-life-care at a facility that, as one patient puts it,'has something very rare and special about it'. PMID- 26268028 TI - Infrastructure for new models of care. AB - The NHS is costing the taxpayer 2.5 times more than it did 50 years ago. Now accounting for 8.2 per cent of the UK's GDP, this trend is set to continue, but funding is not in place to support it. The Government faces a struggle between what is needed and what is affordable, pointing to a complete re-think of the way care is delivered. So says Steve Peak, business development director for Vanguard Healthcare, As the 2015 General Election brings the issue into sharper focus, he examines how estates managers are responding to the pressures and the practicalities of delivering the infrastructure to support a new model of care. PMID- 26268029 TI - Silver biocide's real-world success. AB - Although temperature control has been the UK's longest-serving means of controlling the growth and proliferation of Legionella in hot and cold water systems, there are other factors, including major rises in energy costs, that warrant the use of biocides--including in the healthcare sector. In 2000, the HSE's new 'L8' guidelines took this into account, giving equal weight to both temperature reg~mes and biocides, such as chlorine dioxide, as control methods. Susan Pearson BSc reports on one potentially effective biocide- silver hydrogen peroxide, explains how it 'works' in practice, and highlights the recent 'real world' evidence of its effectiveness and advantages. PMID- 26268030 TI - Case study examples of SHP's successful use. PMID- 26268031 TI - Folding 'health' back into healthcare. AB - David Green, AlA, principal at the London offices of Perkins + Will, and Basak Alkan, AICP, LEED AP/healthcare district planner, at the architect, interior, and urban design company's Atlanta, US base, examine growing moves in the US to re evaluate planning policies to ensure that local environments are built that promote healthy activities, with the creation of so-called 'Health Districts'. Equally, they explain, healthcare 'systems' are starting to see the value in using their campuses to promote this process. In the UK, they argue, 'the timing is perfect for the re-evaluation of the relationship between the medical campus and the city'. PMID- 26268032 TI - It Wasn't Me. PMID- 26268033 TI - Researcher, Dentist, PDA Member: A Conversation with Dr. Steven Jefferies. PMID- 26268035 TI - The LEAN lab: automation, workflow,and efficiency. PMID- 26268034 TI - CLINICOPATHOLOGIC REVIEW. RADIOLUCENCY OF THE JAW ASSOCIATED WITH AN UNERUPTED TOOTH. Adenomatoid odontogenic tumor. PMID- 26268036 TI - Automation and optimization: the importance of the health check. PMID- 26268037 TI - Liquid biopsy: the time is right. PMID- 26268038 TI - Combined primary immune deficiency: diagnosis by clinical flow cytometry. PMID- 26268039 TI - Personalized medicine, pharmacogenomics, and companion diagnostics. Current and future applications of molecular diagnostics will influence these emerging fields. PMID- 26268041 TI - Diabetes: now guidelines for Asian Americans. PMID- 26268040 TI - Paving the way for prediabetes diagnostics: biomarkers that reflect insulin resistance. PMID- 26268042 TI - Digital cell images analyzers in the hematology laboratory. PMID- 26268043 TI - How has the analyzer evolved to meet the needs of the modern molecular diagnostic laboratory? PMID- 26268044 TI - Managing change in the laboratory. PMID- 26268045 TI - Ensuring better patient outcomes through quality waived testing. AB - Waived tests have traditionally been considered to have little or no potential to cause patient harm. But research shows that when workers fail to adhere to such basic instructions as following the directions in manufacturers' inserts, testing errors can occur. PMID- 26268047 TI - Venous Thromboembolism Prophylaxis on a Cardiology In-Patient Unit: A Surprising Result? AB - To determine whether a guideline-based protocol improves compliance with venous thromboembolism (VTE) prophylaxis guidelines, 10 single-day audits of a cardiology inpatient unit were performed. All patients at high risk for VTE were included (n = 420; male/female = 282/138; median age, 66 +/- 14 years). Before the protocol, 36% of patients were not receiving VTE prophylaxis; after the protocol, 26% did not receive prophylaxis (P = 0.024). In conclusion, there is a high rate of noncompliance with accepted guidelines for the prevention of VTE. The introduction of a guideline-based protocol significantly increased compliance, but a substantial proportion of patients still did not receive VTE prophylaxis despite meriting such therapy. PMID- 26268046 TI - Beyond TLR Signaling-The Role of SARM in Antiviral Immune Defense, Apoptosis & Development. AB - SARM (Sterile alpha and armadillo motif-containing protein) is the recently identified TIR domain-containing cytosolic protein. Classified as a member of the TLR adaptor family, the multiple locations and functions of SARM (sometimes playing opposing roles), provoke an enigma on its biology. Although originally assumed to be a member of the TLR adaptor family (functioning as a negative regulator of TLR signaling pathway), latest findings indicate that SARM regulates signaling differently from other TLR adaptor proteins. Recent studies have highlighted the significant functional role of SARM in mediating apoptosis and antiviral innate immune response. In this review, we provide an update on the evolutionary conservation, spatial distribution, and regulated expression of SARM to highlight its diverse functional roles. The review will summarize findings on the known interacting partners of SARM and provide analogy on how they add new dimensions to the current understanding on the multifaceted roles of SARM in antiviral activities and apoptotic functions. In addition, we provide a future perspective on the roles of SARM in differentiation and development, with substantial emphasis on the molecular insights to its mechanisms of action. PMID- 26268048 TI - Practical recommendations for the process of proposing, planning and writing a neurological management guideline by EAN task forces. AB - The European Academy of Neurology (EAN), founded in 2014 after the merging of the two previously active European Neurological Societies, considers the production of neurological guidelines a major obligation, as this is a major tool to improve clinical practice in neurology. This paper updates practical suggestions to develop guidelines about the treatment and diagnosis of neurological diseases within the framework of the EAN. Its aim is to make uniform, traceable and explicit the path from the decision to write an EAN guideline to its publication. We explain the protocol structure, handling of conflicts of interest, format, timeline and process of revision and acceptance. It provides the view of the Scientific Committee and the Board of the EAN. We hope to make easier a larger involvement of the EAN scientific community in producing guidelines. PMID- 26268049 TI - Heidenhain variant in two patients with inherited V210I Creutzfeldt-Jakob disease. AB - OBJECTIVE: To report two members of the same family carrying the valine to isoleucine point mutation of the prion protein gene (PRNP) and presenting with visual symptoms as initial manifestation as in the "Heidenhain variant" of sporadic Creutzfeldt-Jakob disease (CJD). METHODS: Patients underwent neurological examination, electroencephalogram (EEG), brain magnetic resonance images (MRI) and cerebrospinal fluid (CSF) analysis including the Real Time Quaking Induced Conversion (RT-QuIC) test. Disease-specific mutations and polymorphism at codon 129 of the PRNP gene were also studied. RESULTS: Isolated visual symptoms characterized disease onset of both patients followed by progressive neurological signs, dementia and death in 3 (proband) and 9 (his aunt) months. RT-QuIC analysis of CSF samples of both patients revealed the presence of the pathological prion protein and DNA analysis the V210I point mutation of the PRNP and methionine homozygosity at the polymorphic codon 129. CONCLUSIONS: This report suggests to consider the diagnosis of V210I genetic CJD in patients presenting with the Heidenhain form of CJD and highlights the importance of genetic testing in all patients with isolated visual manifestations at onset followed by progressive neurological signs and dementia. PMID- 26268050 TI - Effect of Cation on Physical Properties and CO2 Solubility for Phosphonium-Based Ionic Liquids with 2-Cyanopyrrolide Anions. AB - A series of tetraalkylphosphonium 2-cyanopyrrolide ([Pnnnn][2-CNPyr]) ionic liquids (ILs) were prepared to investigate the effect of cation size on physical properties and CO2 solubility. Each IL was synthesized in our laboratory and characterized by NMR spectroscopy. Their physical properties, including density, viscosity, and ionic conductivity, were determined as a function of temperature and fit to empirical equations. The density gradually increased with decreasing cation size, while the viscosity decreased noticeably. In addition, the [Pnnnn][2 CNPyr] ILs with large cations exhibited relatively low degrees of ionicity based on analysis of the Walden plots. This implies the presence of extensive ion pairing or formation of aggregates resulting from van der Waals interactions between the long hydrocarbon substituents. The CO2 solubility in each IL was measured at 22 degrees C using a volumetric method. While the anion is typically known to be predominantly responsible for the CO2 capture reaction, the [Pnnnn][2 CNPyr] ILs with shorter alkyl chains on the cations exhibited slightly stronger CO2 binding ability than the ILs with longer alkyl chains. We attribute this to the difference in entropy of reaction, as well as the variation in the relative degree of ionicity. PMID- 26268051 TI - Accuracy and interrater reliability of paediatric emergency department triage. AB - OBJECTIVE: To determine the accuracy and reliability of triage of children in public hospital EDs using the Australasian Triage Scale (ATS). This is the first study to examine these issues in paediatric triage following the 2007 development of the Emergency Triage Education Kit (ETEK) to foster accurate and consistent application of the ATS. METHODS: A convenience sample of 167 triage nurses working at three general hospitals and one speciality paediatric hospital in greater metropolitan Melbourne assigned triage ratings for nine paediatric clinical scenarios using the ATS. Scenarios were derived from the ETEK or from other published sources. Kappa was used to assess interrater reliability within and between hospitals. RESULTS: Triage nurses correctly assigned triage scores to an average of 5.3 of nine paediatric clinical scenarios. Accuracy in specific hospitals ranged from a low of 15% on one scenario, to 100% accuracy on a different scenario at a different hospital. Interrater reliability within and across the EDs studied was found to be kappa = 0.27. Both accuracy and interrater reliability were marginally higher at the speciality paediatric hospital. CONCLUSIONS: Our findings demonstrate inconsistencies in the accuracy and reliability in which sick children presenting to EDs receive triage scores both within and across hospitals. These results suggest the need for improvements either in current triage nurse training or training resources. Use of the ETEK alone has not resulted in high levels of paediatric triage accuracy or reliability. PMID- 26268052 TI - [Take a stand for cholesterol theory with LDL-C lowering as the top treatment priority]. PMID- 26268053 TI - [Evaluation of the application of non-statins treatment for dislipidemia]. PMID- 26268054 TI - [A comprehensive understanding of compliance with aspirin therapy]. PMID- 26268055 TI - [Metabolic syndrome and risk of recurrence after catheter ablation of long standing persistent atrial fibrillation]. AB - OBJECTIVE: This study sought to explore the impact of metabolic syndrome (MS) on the risk of recurrence after catheter ablation of long-standing persistent atrial fibrillation (AF). METHODS: Totally 248 patients [197 male, (56+/-12)years] with persistent AF and catheter ablation were included. Long-standing persistent AF was defined based on the duration (more than one year). RESULTS: Among the 248 patients, 96 (38.7%) patients had MS, 130 (52.4%) patients had long-standing persistent AF. After 91-1222 (404+/-303) days follow-up, 119 (47.9%) had recurrence. The recurrence rate was significantly higher in the MS group than that in the non-MS group (58.3% vs 41.4%, P = 0.017). The proportion of MS was similar between the long-standing persistent AF group and the non-long-standing persistent AF group (36.9% vs 40.7%, P = 0.544). Subjects with MS had higher recurrence rate than those without MS in non-long-standing AF group (56.3% vs 32.9%, P = 0.033), but not in long-standing AF group (60.4% vs 48.8%, P = 0.177). In multivariate analysis, MS (hazard ratio 1.98, 95% CI 1.04-3.76, P = 0.036) and AF history duration (hazard ratio 1.04, 95% CI 1.01-1.07, P = 0.004) were independent risk factors for recurrence after catheter ablation of AF. Long standing persistent AF was not an independent risk factor of recurrence. CONCLUSION: MS was natively associated with the success rate of catheter ablation of AF in patients with non-long-standing persistent AF, but not in patients with long-standing persistent AF. PMID- 26268056 TI - [A prospective study on the association of plasma homocysteine level with stroke in hypertensive patients]. AB - OBJECTIVE: To analyze the association between homocysteine (Hcy) and stroke in hypertensive patients. METHODS: This was a prospective cohort study conducted in 60 communities in Nanshan District, Shenzhen. Totally 5 488 patients with hypertension were included at baseline survey and followed for an average of 2.7 years. At the end of follow-up, 327 (5.96%) subjects were missing with unknown reasons. Hcy was detected by enzymatic cycling method. Head CT, MRI, cerebral angiography and transcranial Doppler ultrasound were performed in the patients. Stroke was defined based on the International Classification of Diseases (ICD10 coding I60-I64). RESULTS: After an average of 2.7-year follow-up, 197 developed new stroke. The incidence rate was 3.82%. Subjects whose Hcy levels were within the highest quartile (Q4) had higher risk to develop stroke compared with those whose Hey levels were within the lowest quartile (Q1). The HR (95% CI) were 7.4 (3.2-13.2) in total with 7.5(3.0-19.5) in men and 7.7 (2.7-22.1) in women after adjustment of age, sex, education, smoking, alcohol drinking, and BMI, physical activity, diabetes, depression, family history of stroke or coronary heart disease, years of hypertension, antihypertensive drugs, folic acid, systolic blood pressure, TC, glucose and TG. For every 5 umol/L increase in Hcy, the HR (95% CI) of stroke increased 1.15-fold (1.09-1.21) in total subjects with 1.15 (1.08-1.21) in men and 1.19 (1.04-1.35) in women, respectively. No significant interactions on stroke could be found between Hcy and the above stratified factors. CONCLUSION: Elevated Hcy levels were associated with stroke in hypertensive patients. PMID- 26268057 TI - [The values of the new American Diabetes Association Diagnostic Criteria for screening of pre-diabetes and diabetes in patients undergoing elective coronary angiography]. AB - OBJECTIVE: Glycosylated hemoglobin A1c (HbA1c) has become one of key components in new American Diabetes Association (ADA) diagnostic criteria for pre-diabetes and diabetes, which is not included in the World Health Organization (WHO) 1999 criteria. Thus, we aimed to compare the two criteria in diagnosis of pre-diabetes and diabetes in patients with non-acute coronary syndrome (non-ACS) in Chinese. METHODS: Non-ACS patients who had undergone elective coronary angiography (CAG) in Peking Union Medical College Hospital without previously known diabetes were enrolled consecutively from October 2013 to April 2014. Fasting plasma glucose (FPG), 2-hour plasma glucose after a 75 g oral glucose load (2hPG) and HbA1c levels before CAG were measured. Both WHO and new ADA criteria were applied for pre-diabetes and diabetes screening. RESULTS: One hundred and thirty-nine patients were included, aged (61.9 +/- 10.1) years and 88(63.3%) were men among them. According to WHO 1999 criteria, 34 patients (24.4%) were normal glucose regulation, 57 (41.0%) pre-diabetes (including one impaired fasting glucose and 56 impaired glucose tolerance), and 48 (34.5%) newly diagnosed diabetes mellitus. ADA criteria identified 12 more patients with pre-diabetes and eight more with diabetes than WHO criteria. Compared with those diagnosed by both criteria, the proportion of women was higher in diabetic patients diagnosed with HbA1c alone. They also had lower hemoglobin [(124.88 +/- 17.74) g/L vs (140.15 +/- 15.17) g/L, P=0.013] and higher fibrinogen levels [(3.47 +/- 0.41) g/L vs (3.02 +/- 0.68) g/L, P=0.024] than those diagnosed by both criteria. CONCLUSION: Compared with WHO 1999, new ADA criteria with HbA1c assessment are able to identify more previously unknown pre-diabetes and diabetes patients. Measurement of HbA1c might be needed to carry out routinely for screening patients with glucose metabolism abnormalities before elective CAG. PMID- 26268058 TI - [The efficacy and safety of human glucagon-like peptide-1 analogue liraglutide in newly diagnosed type 2 diabetes with glycosylated hemoglobin A1c > 9]. AB - OBJECTIVE: To evaluate the efficacy and safety of human glucagon-like peptide-1 analogue liraglutide in newly diagnosed type 2 diabetes mellitus (T2DM) with glycosylated hemoglobin A1c (HbA1c) > 9%. METHODS: This was an open-labelled, randomized, parallel-group, treat-to-target trial. Newly diagnosed T2DM patients with HbA1c > 9% were enrolled. These patients were treated with metformin with repaglinide and randomized to receive once-daily liraglutide (LIRA, n=25) or the insulin glargine (IGla, n=24) at bedtime. Efficacy and safety were assessed and compared after 18-month treatment. RESULTS: (1) Compared with the baseline, patients with LIRA had significantly reduced mean body weight,BMI and waist circumference (P < 0.01), whereas, the above indexes were increased (P < 0.01) in patients treated with IGla. (2) After 18 months of treatment, fasting plasma glucose (FPG), 2-hour plasma glucose after a 75g oral glucose load (2hPG) and HbA1c were significantly improved in all patients (P < 0.01), with 2hPG, mean blood glucose (MBG), the largest amplitude of glycemic excursions (LAGE), mean amplitude of glycemic excursions (MAGE) were significantly lower in LIRA group than in IGla group (all P < 0.05). (3) HOMA-IR decreased in both groups (P < 0.05). However, DeltaI30/DeltaG30, AUCCP180 and Matsuda index were only significantly increased in patients treated with LIRA (respectively, 4.88 +/- 1.55 vs 7.60+/-1.91, 9.23 +/- 2.66 vs 13.18 +/- 2.72, 39.28 +/- 20.35 vs 54.64 +/ 23.34, all P < 0.01), while HOMA-IR reduced (4.41 +/- 1.58 vs 3.52 +/- 1.44, P < 0.05). But in IGla group only HOMA-IR was reduced (4.92 +/- 1.84 vs 4.57 +/- 1.80, P < 0.05). The index of DeltaI30/DeltaG30, AUCCP180 and Matsuda index in LIRA group are higher than those of indexes in IGla group(respectively, 7.60 +/- 1.91 vs 4.18 +/- 1.00, 13.18 +/- 2.72 vs 10.53 +/- 2.68,54.64 +/- 23.34 vs 41.65 +/- 17.84, all P < 0.05), while HOMA-IR is lower (3.52 +/- 1.44 vs 4.57 +/- 1.80, P< 0.05). (4) The rate of HbA1c <= 6.5% and the dosages of oral anti-diabetic drugs in LIRA group were significantly better than that in IGla group. (5) No significant differences were observed in hypoglycemic episodes and adverse events between two groups. CONCLUSION: It seems that liraglutide is superior to insulin glargine in newly diagnosed T2DM patients with HbA1c > 9% in improving beta-cell function, insulin sensitivity and glucose homeostasis. PMID- 26268059 TI - [Investigation of the risk of hepatitis B virus reactivation in arthritis patients undergoing anti-tumour necrosis factor alpha therapy]. AB - OBJECTIVE: To investigate the prevalence of HBV infection and the risk of hepatitis B virus (HBV) reactivation in patients with inflammatory arthritis receiving tumour hecrosis factor alpha (TNFalpha) inhibitors. METHODS: The liver function, serology of HBV and viral loads (HBV DNA) were tested before using TNFalpha inhibitors, at 3 months and 6 months. Patients with chronic hepatitis B (CHB) infection (HBV DNA > 1*10(3) copies/ml) were eliminated. RESULTS: A total of 162 patients were investigated including 156 patients who finished the study. Eleven (7.05%) patients were HBsAg-positive. Two patients with HBV DNA > 1*10(3) copies/ml were eliminated before starting anti-TNFalpha therapy. Among HBsAg positive patients, HBV reactivation was documented in only one of the 11 patients. This patient with rheumatoid arthritis developed elevation of glutamic pyruvic transaminase (ALT) and HBV DNA copies three months after infliximab therapy. Therefore lamivudine was given for three months, which translated into the fall of ALT and HBV DNA copies back to normal level. After follow-up for six months, the virology and serology remained stable. In contrast, none of the other 155 patients had demonstrated evidence of HBV infection or HBV reactivation. CONCLUSION: The kinetics of HBV viral loads should be carefully monitored in patients with inflammatory arthritis and HBsAg-positive during anti-TNFalpha therapy. HBV reactivation should be treated with antiviral medicine through out the period of anti-TNFalpha therapy. PMID- 26268060 TI - [1,25(OH)2-Vitamin-D3 attenuates Th17-related cytokines expression in peripheral blood mononuclear cells in patients with early-diagnosed rheumatoid arthritis]. AB - OBJECTIVE: To investigate the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on T helper cell type 17 (Th17) cytokines and therapeutic mechanism in patients with rheumatoid arthritis (RA). METHODS: Peripheral blood mononuclear cells (PBMCs) from healthy donors and RA patients were collected. The PBMCs were stimulated with anti-CD3/anti-CD28 monoclonal antibodies in the absence or presence of 1,25(OH)2D3and methotrexate (MTX). After co-culture, the serum levels of Th17 cytokines interleukin (IL)-17, IL-6, tumour necrosis factor alpha (TNFalpha) were analyzed by cytometric bead array (CBA). The level of IL-22 was analyzed by enzyme-linked immunosorbent assay (ELISA). The independent samples t test and one-way analysis of variance (ANOVA) were used for statistical analysis. RESULTS: The levels of cytokines IL-17, TNFalpha, IL-6 and IL-22 in RA group were significantly higher than those in the control group [(43 +/- 6)ng/L, (5.91 +/- 2.53)ng/L, (16.6 +/- 12.0)ng/L, (51 +/- 17)ng/L vs (21 +/- 3)ng/L, (2.63 +/- 0.27)ng/L, (4.2+/-2.3)ng/L, (22 +/- 14)ng/L]. Each of the three different 1,25(OH)2D3doses inhibited secretion of IL-17[(533 +/- 47) pg/ml, (426 +/- 55)pg/ml, (319 +/- 86)pg/ml], TNFalpha[(424 +/- 82)pg/ml, (382 +/- 79)pg/ml, (326 +/- 87)pg/ml], and IL-6[(5 513 +/- 3 429)pg/ml, (4 555 +/- 3 157)pg/ml, (3 748 +/ 1 919)pg/ml] in RA group (P < 0.05), yet no statistical difference was found in IL-22 secretion with a trend of decrease after treatment of 1,25(OH)2D3. Three different doses of MTX inhibited secretion of IL-17 [(452 +/- 50) pg/ml, (372 +/- 67) pg/ml, (315 +/- 104)pg/ml] and TNFalpha [(319 +/- 74)pg/ml, (292 +/- 59)pg/ml, (266 +/- 64)pg/ml] in RA group (P < 0.05).However, levels of IL-6 and IL-22 were not affected after treated with MTX. CONCLUSION: Our data indicated that 1,25(OH)2D3may play as an immune modulating agent to suppress Th17 cell cytokines. Supplement of vitamin D has the effective potential to treat patients with RA or other Th17 cell mediated autoimmune disorders. PMID- 26268061 TI - [A clinical analysis of onset of high-risk demyelinating events in patients with neuromyelitis optica]. AB - OBJECTIVE: To explore the clinical characteristics of the lesions of spinal cord and optic nerve as the onset of neuromyelitis optica (NMO). METHODS: A total of fifty-one patients with myelitis or optic neuritis (ON) as the onset of NMO who hospitalized in our Neurology Department during October 2010 to October 2012 were enrolled in the study. Clinical presentations and MRI findings of the spinal cord and brain were studied. RESULTS: (1) A total of 26 cases (51.0%) presented with myelitis as the index event, in which 30.8% (8/26) were the longitudinally extensive transverse myelitis (LETM) and 69.2% (18/26) were non-LETM (short segmental myelitis or non-transverse myelitis). Patients with non-LETM as the onset were found to have better prognosis than those with LETM (full recovery ratio was 13/18 vs 2/8, P < 0.05), while shorter recurrence interval of myelitis and higher recurrence frequency of events were shown in patients with non-LETM (11.1 vs 18.6 months, 3 times per year vs once per year, with all P < 0.05). (2) A total of 25 cases (49.0%) presented with ON as the index event with 24.0% (6/25) of unilateral ON and 76.0% (19/25) of bilateral ON. Patients with bilateral ON had more severe visual impairment and shorter first remission period than those with unilateral ON (P < 0.05). CONCLUSION: Non-LETM and bilateral ON are the most common index demyelinating events in NMO cases. PMID- 26268062 TI - [An analysis for the clinical difference between post infectious irritable bowel syndrome and non post infectious irritable bowel syndrome]. AB - OBJECTIVE: To study the clinical discrepancy between patients with post infectious irritable bowel syndrome (PI-IBS) and non post infectious irritable bowel syndrome (NPI-IBS) , and assess the value of serum intestinal fatty acid binding protein (I-FABP) for differential diagnosis. METHODS: A total of 117 patients with PI-IBS, 201 patients with NPI-IBS and 31 healthy controls were prospectively recruited in General Liberation Army Hospital from 2010 to 2013. Plasma samples and clinical data were collected. Serum I-FABP level was measured by an enzyme-linked immunosorbent assay. RESULTS: The median age of patients with PI-IBS was 36 years. The median time to diagnosis in PI-IBS group was significantly longer than that in NPI-IBS group [(19.7 +/- 10.3)months vs (11.4 +/- 5.3) months, P < 0.05]. Similarly, the proportion of anxiety [58.1%(68/117) vs 28.9%(58/201), P < 0.05] and the value of I-FABP [(42.6 +/- 14.8) ug/L vs (17.3 +/- 11.5) ug/L, P < 0.05] in PI-IBS group were significant higher than NPI IBS patients. The level of I-FABP of healthy controls [(10.6 +/- 8.2) ug/L] was also significantly lower than that of PI-IBS patients (P < 0.05), yet no difference from that of NPI-IBS group. The I-FABP value of subgroup PI-IBS patients with diarrhoea (IBS-D) was significant higher than that of NPI-IBS group [(54.8 +/- 9.3)ug/L vs (12.3 +/- 6.2) ug/L, P < 0.05]. However, other parameters including gender, age, GSRS score, and I-FABP value of subgroup constipation (IBS C) and mix (IBS-M), were not different between PI-IBS group and NPI-IBS group (all P > 0.05). CONCLUSION: PI-IBS is an occult intestinal inflammation disease with mucosa injury. I-FABP might be a potential testing marker for the diagnosis of PI-IBS. PMID- 26268063 TI - Proliferative activity in melanocytic nevi from patients grouped by age with clinical follow-up. AB - Any mitotic activity in a melanocytic nevus is a source of concern about the biologic potential of that lesion, especially in an adult. Previously diagnosed benign melanocytic nevi in individuals from six different age groups were re examined; mitotic figures were counted in routine hematoxylin and eosin-stained sections; Ki-67 nuclear positivity was assessed by immunohistochemistry. Mitoses were seen in 0-14.3% of nevi in all groups of patients >1 year of age; 55.6% (5/9 cases) of nevi in patients <1-year old had mitoses identified histologically. Ki 67-positive melanocytes were seen in all cases of those lesions in infants (less than 1-year old) and only in a minority of lesions from the other age groups. The maximum and mean numbers of Ki-67-positive melanocytes per square millimeter were highest in patients <1-year old (16.7 and 5.6, respectively), and decreased in all other groups. Follow-up data were available in the majority of the patients. There were no examples of malignant melanoma in the various age groups. We conclude that proliferative activity in benign melanocytic nevi decreases with age, however, proliferative activity can be seen at any age and its significance must be judged in the context of other histopathologic features. PMID- 26268064 TI - Enhancing Effect of Trachelogenin from Trachelospermi caulis Extract on Intestinal Barrier Function. AB - Trachelospermi caulis is used widely as an herbal medicine in oriental countries to attenuate fever and pain. We wished to reveal the novel function of this herb and its active component on barrier function in intestinal epithelial cells. Monolayers of intestinal epithelial cells (Caco-2) were used to evaluate the transepithelial electrical resistance (TEER) and quantity of permeated ovalbumin (OVA) as indices of barrier function. T. caulis increased TEER values on cell monolayers and decreased OVA permeation across cell monolayers. To ascertain the active component of T. caulis, the extract was isolated to five fractions, and the effect of each of these fractions on intestinal barrier function examined. Chloroform and ethyl acetate fractions showed increased TEER values and decreased OVA flux. Chloroform and ethyl acetate fractions contained mainly trachelogenin and its glycoside, tracheloside. Trachelogenin increased TEER values and decreased OVA flux by enhancing the tight-junction protein occludin (but not tracheloside) in Caco-2 monolayers. These findings demonstrated that trachelogenin, an active component of T. caulis, might help to attenuate food allergy or inflammatory bowel disease through inhibition of allergen permeation or enhancement of the intestinal barrier. PMID- 26268065 TI - Vaccination with Recombinant Non-transmembrane Domain of Protein Mannosyltransferase 4 Improves Survival during Murine Disseminated Candidiasis. AB - Candida albicans is the most common cause of invasive fungal infections in humans. The C. albicans cell wall proteins play an important role in crucial host fungus interactions and might be ideal vaccine targets to induce protective immune response in host. Meanwhile, protein that is specific to C. albicans is also an ideal target of vaccine. In this study, 11 proteins involving cell wall biosynthesis, yeast-to-hypha formation, or specific to C. albicans were chosen and were successfully cloned, purified and verified. The immune protection of vaccination with each recombinant protein respectively in preventing systemic candidiasis in BALB/c mice was assessed. The injection of rPmt4p vaccination significantly increased survival rate, decreased fungal burdens in the heart, liver, brain, and kidneys, and increased serum levels of both immunoglobulin G (IgG) and IgM against rPmt4p in the immunized mice. Histopathological assessment demonstrated that rPmt4p vaccination protected the tissue structure, and decreased the infiltration of inflammatory cells. Passive transfer of the rPmt4p immunized serum increased survival rate against murine systemic candidiasis and significantly reduced organ fungal burden. The immune serum enhanced mouse neutrophil killing activity by directly neutralizing rPmt4p effects in vitro. Levels of interleukin (IL)-4, IL-10, IL-12p70, IL-17A and tumor necrosis factor (TNF)-alpha in serum were higher in the immunized mice compared to those in the adjuvant control group. In conclusion, our results suggested that rPmt4p vaccination may be considered as a potential vaccine candidate against systemic candidiasis. PMID- 26268066 TI - Reevaluating the two-representation model of numerical magnitude processing. AB - One debate in mathematical cognition centers on the single-representation model versus the two-representation model. Using an improved number Stroop paradigm (i.e., systematically manipulating physical size distance), in the present study we tested the predictions of the two models for number magnitude processing. The results supported the single-representation model and, more importantly, explained how a design problem (failure to manipulate physical size distance) and an analytical problem (failure to consider the interaction between congruity and task-irrelevant numerical distance) might have contributed to the evidence used to support the two-representation model. This study, therefore, can help settle the debate between the single-representation and two-representation models. PMID- 26268067 TI - Conflict or Caveats? Effects of Media Portrayals of Scientific Uncertainty on Audience Perceptions of New Technologies. AB - Research indicates that uncertainty in science news stories affects public assessment of risk and uncertainty. However, the form in which uncertainty is presented may also affect people's risk and uncertainty assessments. For example, a news story that features an expert discussing both what is known and what is unknown about a topic may convey a different form of scientific uncertainty than a story that features two experts who hold conflicting opinions about the status of scientific knowledge of the topic, even when both stories contain the same information about knowledge and its boundaries. This study focuses on audience uncertainty and risk perceptions regarding the emerging science of nanotechnology by manipulating whether uncertainty in a news story about potential risks is attributed to expert sources in the form of caveats (individual uncertainty) or conflicting viewpoints (collective uncertainty). Results suggest that the type of uncertainty portrayed does not impact audience feelings of uncertainty or risk perceptions directly. Rather, the presentation of the story influences risk perceptions only among those who are highly deferent to scientific authority. Implications for risk communication theory and practice are discussed. PMID- 26268068 TI - The relationship between microfilaraemic and amicrofilaraemic loiasis involving co-infection with Mansonella perstans and clinical symptoms in an exposed population from Gabon. AB - The relationship between the frequency of loiasis objective symptoms and microfilaraemic or amicrofilaraemic infection was assessed in 1148 exposed patients also infected, or not, with Mansonella perstans. Filarial infections were detected by direct microscopy, leucoconcentration and serology, with prevalence values of 39.5% Loa loa, 5.6% M. perstans and 3.4% co-infection with both filarial species. Amicrofilaraemic or occult loiasis (OL) predominated among L. loa-infected individuals, with a prevalence of 58.2%. Hypermicrofilaraemia (>8000 microfilariae (mf)/ml) was found in 18.4% of L. loa microfilaraemic patients, with 25.7% of them harbouring more than 30,000 mf/ml. Up to 34% of patients with OL showed evidence of Calabar swelling, compared with 26.3% of microfilaraemic patients (P= 0.03). Overall 5.3% of patients presented with adult worm migration across the eye, representing 16.3% of microfilaraemic individuals and 11.4% of amicrofilaraemic patients (P= 0.13). This symptom was similarly found in patients with more than 30,000 mf/ml (22%), those with microfilaraemia between 8 and 30,000 mf/ml (15.4%) and also in individuals with low or without microfilaraemia (16.1%) (P= 0.7). Five (14.3%) hypermicrofilaraemic patients did not present any L. loa-specific objective symptoms, as well as all the patients with single M. perstans infection. The presence of adult eye worm migration as a strong predictor of high microfilaraemia density would obscure the real burden of L. loa hypermicrofilaraemia in exposed individuals. For epidemiological purposes and control strategies, the mapping of L. loa in endemic areas should also take into account the group of patients with occult loiasis. PMID- 26268069 TI - An island of stability in a sea of fingers: emergent global features of the viscous-flow instability. AB - The displacement of a more viscous fluid by a less viscous one in a quasi-two dimensional geometry leads to the formation of complex fingering patterns. This fingering has been characterized by a most unstable wavelength, lambdac, which depends on the viscosity difference between two immiscible fluids and sets the characteristic width of the fingers. How the finger length grows after the instability occurs is an equally important, but previously overlooked, aspect that characterizes the global features of the patterns. Long after the instability onset, once the fingers are growing in a nearly steady-state regime, there is a stable inner region where the outer fluid is completely displaced. We show that the ratio of the finger length to the radius of this stable region depends only on the viscosity ratio of the fluids and is decoupled from lambdac. PMID- 26268070 TI - Home nurses' turnover intentions: the impact of informal supervisory feedback and self-efficacy. AB - AIM: To examine how home nurses' turnover intentions are affected by the quality and frequency of supervisory feedback and by their own self-efficacy. BACKGROUND: Little is known about effective retention strategies for the growing home healthcare sector that struggles to retain an adequate workforce. While the work environment and supervisors have been found to play a key-role in nurses' turnover intentions, home nurses mostly work autonomously and apart from their supervisors. These circumstances require a customized approach and need to be understood to ensure high-quality home health care. DESIGN: We used a correlational, cross-sectional survey design. METHOD: A convenience sample of 312 home nurses was selected from a division of a large home health care organization in Flanders, Belgium. Data were collected in 2013 using structured questionnaires and analysed using descriptive statistics, structural equation modelling and relative weight analysis. RESULTS: The quality of feedback was related to lower levels of turnover intentions. This relationship was fully mediated by home nurses' self-efficacy. Frequent favourable feedback was directly related to lower turnover intentions while the relationship between frequent unfavourable feedback and turnover intentions was conditional on home nurses' level of self-efficacy. CONCLUSION: This study contributes to our understanding of home nurses' turnover intentions and the role of informal supervisory feedback and home nurses' self efficacy. PMID- 26268072 TI - Intentional continuous shallowing of the anterior chamber, a procedure to prevent lens touch during phakic vitrectomy. PMID- 26268071 TI - Microbial eukaryotic diversity and distribution in a river plume and cyclonic eddy-influenced ecosystem in the South China Sea. AB - To evaluate microbial eukaryotic diversity and distribution in mesoscale processes, we investigated 18S rDNA diversity in a river plume and cyclonic eddy influenced ecosystem in the southwestern South China Sea (SCS). Restriction fragment length polymorphism analysis was carried out using multiple primer sets. Relative to a wide range of previous similar studies, we observed a significantly higher proportion of sequences of pigmented taxa. Among the photosynthetic groups, Haptophyta accounted for 27.7% of the sequenced clones, which belonged primarily to Prymnesiophyceae. Unexpectedly, five operational taxonomic units of Cryptophyta were closely related to freshwater species. The Chlorophyta mostly fell within the Prasinophyceae, which was comprised of six clades, including Clade III, which is detected in the SCS for the first time in this study. Among the photosynthetic stramenopiles, Chrysophyceae was the most diverse taxon, which included seven clades. The majority of 18S rDNA sequences affiliated with the Dictyochophyceae, Eustigmatophyceae, and Pelagophyceae were closely related to those of pure cultures. The results of redundancy analysis and the permutation Mantel test based on unweighted UniFrac distances, conducted for spatial analyses of the Haptophyta subclades suggested that the Mekong River plume and cyclonic eddy play important roles in regulating microbial eukaryotic diversity and distribution in the southwestern SCS. PMID- 26268073 TI - [CONSENSUS ON FATS AND OILS IN THE DIET OF S ISH ADULTS; POSITION PAPER OF THE SPANISH FEDERATION OF FOOD, NUTRITION AND DIETETICS SOCIETIES]. AB - The quality of dietary fat critically influences health. In this consensus document the scientific evidence relating effects of dietary fat quantity and quality on cardiovascular risk is reviewed and recommendations for the Spanish adult population are issued. As a novelty in nutrition guidelines, emphasis is made more on parent foods than on fatty acids per se. In summary, replacing saturated fatty acids (SFA) for monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) reduces cardiovascular risk. Recent data suggest that SFA proper may be harmful or not depending on the parent food, a reason why an intake threshold is not established, but consumption of foods containing excess SFA, such as butter, some processed meats, and commercial confectionery and fried foods is discouraged. The established threshold of <1 % of energy intake as trans FA, well known to be harmful for cardiovascular risk, is fulfilled in Spain due in part to its present low levels in margarines. MUFA are beneficial or neutral for cardiovascular risk depending on their dietary sources (virgin olive oil versus other fats), and no intake limitations are established.n-6 PUFA are cardioprotective and recommended intakes (5-10 % of energy) are not always fulfilled in the Spanish population, thus increased consumption of their vegetable food sources (seeds, derived oils, and margarines)is encouraged. Marine n-3 PUFA are also cardioprotective and the recommendation stands to eat fatty fish>=2 servings/weeks to reach intake levels of at least 250 mg/day. Increasing evidence suggests that alpha-linolenic acid (ALA), the vegetable n-3 PUFA, is also cardioprotective,but the parent foods (walnuts, soy products,green-leaf vegetables) may provide benefits beyond ALA itself. Finally, low-fat (high carbohydrate, particularly when having a high glycemic index) diets appear to lack cardiovascular preventive effects, while high-fat,high-vegetable fat dietary patterns such as the Mediterranean diet, are protective, a reason why no upper limit on fat intake is established for the Spanish population.This position statement targets dietitians, nutritionists and other health professionals involved in dietary counsel so they can deliver it rightly and according to the last scientific evidence. PMID- 26268074 TI - [PHARMACONUTRITION IN SEVERELY ILL PATIENT]. AB - "Pharmaconutrient" is a term applicable to those compounds which. in addition to their nutritional function, play a role as aids in the treatment of patients with severe pathologies, including sepsis, trauma, burns and major surgery, In general, enrichment of enteral an parenteral formulas with pharmaconutrients contribute to positively modulate the inflammatory response, infection and controlling the internal milieu, which in turn can be evaluated through lower mortality, hospital and intensive care units stay, days of mechanical ventilation and other parameters allowing to asses their effects. Arginine, glutamine, nucleotides, omega-3 fatty acids and antioxidant micronutrients, make up the nucleus of pharmaconutrients used with that aim, usually as mixtures of them. In the present review current evidence about the effects, indications, limitations, doses, potential adverse risks and even counter-indications is analysed. PMID- 26268075 TI - GENETIC VARIATION IN THE BETA-3-ADRENORECEPTOR GENE (TRP64ARG POLYMORPHISM) AND THEIR INFLUENCE ON ANTHROPOMETRIC PARAMETERS AND INSULIN RESISTANCE AFTER A HIGH PROTEIN/LOW CARBOHYDRATE VERSUS A STANDARD HYPOCALORIC DIET. AB - INTRODUCTION: the Trp64Arg variant in Beta receptor has been reported to be associated with increased body weight and insulin resistance Objective: the aim of our study was to investigate the influence of polymorphism (rs 4994) in Beta-3 adrenergic receptor gene on metabolic response and weight loss in a medium-term intervention study secondary's to a high protein/low carbohydrate vs. a standard hypocaloric diets (1000 kcal/day). MATERIAL AND METHODS: a population of 284 obese subjects was analyzed in a randomized trial. A nutritional evaluation was performed at the beginning and at the end of a 9-month period in which subjects received 1 of 2 diets (diet HP: high protein/low carbohydrate vs diet S: standard diet). RESULTS: there were no significant differences between the positive effects (on weight, BMI, waist circumference, fat mass, systolic blood pressure and leptin levels) in either genotype group with both diets. With both diets and only in wild genotype (diet HP vs diet S), total cholesterol (-10.1 +/- 3.9 mg/dl vs -10.1 +/- 2.2 mg/dl;p>0.05), LDL cholesterol (-9.5 +/- 2.1 mg/dl vs -8.5 +/- 2.3 mg/dl;p>0.05) and triglycerides (-19.1 +/- 2.1 mg/dl vs -14.3 +/- 2.1 mg/dl;p>0.05) decreased. The improvement in these parameters was similar in subjects with diet HP than HS. With diet HP and only in wild genotype, insulin levels (-3.7 +/- 1.9 UI/L;p<0.05) and HOMA-R (-0.7 +/- 0.1 units;p<0.05) decreased. CONCLUSION: metabolic effect of weight reduction by two hypocaloric diets is the greatest in subjects with normal homozygous beta 3-AR gene. Improvement in total cholesterol, LDL-cholesterol, triglyceride, glucose, insulin and HOMA-R levels is better than in the heterozygous group. PMID- 26268076 TI - [SPIRULINA AND ITS HYPOLIPIDEMIC AND ANTIOXIDANT EFFECTS IN HUMANS: A SYSTEMATIC REVIEW]. AB - Several chronic transmissible (e.g. AIDS) and non transmissible diseases like cadiovascular disease, are associated with oxidative stress (EOX) and dyslipidemia. Has been reported that Spirulina can reduce them, this has been demonstrated in vitro and in animal models but scarcely in humans. Through a systematic review on last 5 years (keywords: Spirulina AND cholesterol, Spirulina AND oxidative stress) 8 intervention studies with humans were reported, finding that oral (1-10 g/d) subchronic (0.5-6 month) administration of Spirulina appears to have and hypolipidemic and antioxidant effect. However, no study was properly randomized and/or controlled and no biological mechanism was proposed to support these findings. The level of evidence and the absence of appropriate experimental designs do not allow validating Spirulina as a functional food for preventing dyslipidemic diseases and EOX, and hereby decrease the CVD. We do not found papers relating harmful effect. PMID- 26268077 TI - THE EFFECT OF PROBIOTIC FERMENTED MILK THAT INCLUDES BIFIDOBACTERIUM LACTIS CNCM I-2494 ON THE REDUCTION OF GASTROINTESTINAL DISCOMFORT AND SYMPTOMS IN ADULTS: A NARRATIVE REVIEW. AB - AIM: determine the effectiveness of fermented milk that included Bifidobacterium lactis CNCM I-2429 for reducing gastrointestinal (GI) discomfort in healthy adults. METHODS: we conducted a systematic literature search to identify studies reporting the use of B. animalis spp. lactis for GI discomfort/comfort in healthy adults. A total of 5329 records were identified, of these 99 full-text articles were assessed. Searches for additional trials were conducted using the names of authors of each identified study and several relevant databases. The study selection was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were included if they were randomized controlled trials; the included subjects were healthy adults; and the intervention group received B. lactis CNCM I-2494. Studies were excluded if they were non-randomized trials, if they included adults who were not healthy, if they included the use of any other intervention, or if they compared different products without a placebo group. The methodological quality of the studies was evaluated using the Oxford Quality Scale and the Cochrane Concealment Assessment. A meta-analysis was not possible. RESULTS: the search strategy identified two studies that included a total of 538 healthy women, aged 18-60 years, normal weight or overweight (BMI 18-30 kg/m2). GI well-being was significantly improved in the Probiotic group vs. the Control group in one study, with no differences in the other. The percentage of responders for GI well-being was higher in the Probiotic group vs. the Control group in the first study but not in the second. GI symptoms were significantly decreased in the Probiotic group vs. the Control group in both studies. Bowel function was assessed by one study; the stool frequency did not differ between the groups, but a decrease in stool consistency was observed in the Probiotic group but not in the Control group. Possible mechanisms of action (gut motility, hypersensitivity, gut permeability, and gut microbiota) were also described. CONCLUSION: probiotic fermented milk containing B. lactis CNCM I-2494 by healthy women may improve GI well- being and decrease the frequency of GI symptoms. PMID- 26268078 TI - SYSTEMATIC REVIEW OF HEALTHY EATING INDEXES IN ADULTS AND ELDERLY: APPLICABILITY AND VALIDITY. AB - INTRODUCTION: The Healthy Eating Index (HEI) assesses a combination of different types of foods, nutrients and dietary components. It has been adapted in some countries, considering the local dietary habits. OBJECTIVE: in this article, the Healthy Eating Indexes published to date were identified by means of a systematic review. Besides, issues relating to their validity, applicability and limitations were discussed. METHODS: an electronic search was performed in the PUBMED, SCIENCE DIRECT, BVS and SciELO data base containing studies on the adaptation, review, update or validation of the HEI. The descriptors Healthy Eating Index, Index of Diet Quality, Quality of diet, Diet surveys were used, in different combinations. RESULTS: a total of 11 studies were described and critically analyzed. One of the studies dealt with the development of the index; six proposed adjustments; two assessed validity and reliability of the index, and the other two proposed revision and update. The Healthy Eating Indexes reveal the actual quality of the diet, but the absence of a methodological standard hinders the comparison of the results found in different populations. PMID- 26268080 TI - EFFECT OF EICOSAPENTAENOIC ACID AND DOCOSAHEXAENOIC ACID SUPPLEMENTATIONS TO CONTROL COGNITIVE DECLINE IN DEMENTIA AND ALZHEIMER'S DISEASE: A SYSTEMATIC REVIEW. AB - INTRODUCTION: there is a lack of consensus on the benefits of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementations on cognition in dementia and/or Alzheimer's disease (AD) elderly. OBJECTIVE: this study presents a systematic review of the results of randomized clinical trials about this topic. The adopted search criteria were randomized clinical trials involving elderly over 65 years of age with no limit to the year of publication of the study. RESULTS: we identified 139 articles, and from the eligible ones a reverse search was conducted. The quality of the trials was assessed using the Jadad scale. Of the four selected studies, three were related to mild to moderate AD elderly, of both genders. Mini Mental State Examination, Alzheimer's Disease Assessment Scale Cognitive, and Clinical Dementia Rate were the main tests used to assess cognitive performance. CONCLUSION: EPA and/or DHA supplementations did not affect scores obtained on the cognitive tests. However, supplementation with EPA and/or DHA improved verbal fluency and attention in patients who had only very mild dementia or AD or presented APOEepsilon4 negative genotype. In case of advanced AD elderly patients, EPA and/or DHA supplementations did not reduce cognitive decline rates. PMID- 26268079 TI - [TRIGLYCERIDE LEVELS AS A RISK FACTOR DURING PREGNANCY; BIOLOGICAL MODELING; SYSTEMATIC REVIEW]. AB - INTRODUCTION: introduction: Some of the diseases that can appear in pregnancy (gestational diabetes, hypertension and preeclampsia) are being associated with an increased risk of heart throughout life diseases. This should be present in future assessments of the health of women. One of the most important biomarkers in cardiovascular diseases is the triglyceride level, and that undergoes a significant change during pregnancy. OBJECTIVE: the objective of this review is to analyze the studies that have investigated triglyceride levels during pregnancy as a risk factor for cardiovascular disease in the last weeks of pregnancy and childbirth. METHODS: a systematic search was made and 14 specific articles on the subject were selected following the PRISMA guidelines. RESULTS: in normal pregnancy decreased the level of lipids in the first weeks, followed by a gradual increase. Especially high from the 12th week of gestation. This increase in plasma levels of circulating lipids occurs linearly, reaching a peak a few days before delivery. This increase results because of the increased estrogen levels and insulin resistance. It has also been associated with prolactin levels. CONCLUSIONS: through this review, it has been able to demonstrate the relationship of elevated triglycerides some pathologies or more frequent changes in risk pregnancies, in which a significantly higher elevation occurs compared to normal pregnancies. It is in this context that the biological modeling may be particularly important, facilitating the creation of models and percentile curves applicable to the population, and allow monitoring of changes in triglycerides, which end up pointing situations passing be predictors of a potentially pathological situation. Thus, appropriate interventions would be carried rafter more briefly, and see so favored adequate primary prevention. PMID- 26268081 TI - [EFFECTS OF SCHOOL-BASED PHYSICAL ACTIVITY AND NUTRITION PROGRAMS IN SPANISH ADOLESCENTS: SYSTEMATIC REVIEW]. AB - BACKGROUND: physical inactivity and unhealthy nutrition behaviours in early ages are two of the biggest problems related with public health in developed countries. AIMS: to carry out a systematic review of school-based programs related with physical activity promotion and/or nutrition in adolescents implemented in Spain and published in the principal national and international data bases in the last 15 years. METHOD: the literature was searched in spanish and english data bases Web of Science, ERIC, PsycINFO, Dialnet and ISOC, following PRISMA declaration principles for systematic reviews. RESULTS AND DISCUSSION: from a total of 522 references, were retained 13 studies due to inclusion criteria. The most prevalent programs included families participation in the intervention. At the same time, the Physical Education teachers and the health personnel were the principal actor in programs development. Both of them were the principal protagonist in interventions. All the programs were able to improve at least one of the variables. CONCLUSION: were identified only 13 school based intervention programs related with physical activity and/or nutrition in adolescents in the last 15 years in Spain. All the programs reached improvements, so school shows a relevant role in acquisition or improvement of this health behavior. PMID- 26268082 TI - [ADVANCES IN PHARMACOLOGICAL AND PHYTOCHEMICAL ADIPOGENESIS THERAPY]. AB - The main function of the adipocyte is lipid storage when there is a positive energy balance and lipid release when there is and energy deficiency. One characteristic of obesity is an increase in the number and size of adipocytes, which implies pre adipocyte (PAD) differentiation. The adipose tissue (AT) has its origins in the prenatal stage and may continue to expand during adulthood from precursor cells since mature adipocytes cannot multiply by cell division. This study provide updates on the events that occur during the origin and differentiation of PAD, the factors involved in the regulation of adipogenesis and mechanisms that regulate physiological functions of AT. PMID- 26268083 TI - [VARIABLES USED IN QUESTIONNAIRES ABOUT ERGONUTRITIONALS SUPPLEMENTS INTAKE]. AB - INTRODUCTION: nutritional supplements intake is increasing during the recent years both in Spain and in the rest of the world. Questionnaires that estimate the intake and supplement use have methodological limitations. The purpose of this study is to describe used indicators in questionnaires that estimate nutritional supplements intake among athletes so facilitate understanding of these limitations. METHODOLOGY: a literature review of variables used within questionnaires to estimate consumption of nutritional supplements among athletes. We conducted a structured research in PubMed database and through snow ball strategy. Search equation: "Questionnaire" AND "Supplementation" AND "Athletes". INCLUSION CRITERIA: published in any country in English or Spanish, containing questionnaire or indicators can be deducted from the items, to estimate the intake and use of nutritional supplements and should be targeted to athletes training in order to compete at any level. We performed a descriptive analysis. RESULTS: 21 above the 122 identified studies met the inclusion criteria. Sociodemographic factors, sport and training frequency, athlete population, reasons/motives for use and consumption, sources of information and list of supplements and frequency are the found indicators for estimating intake of supplements. DISCUSSION: there are great heterogeneity in terms of the proposed indicators by the authors at the questionnaires and intake estimation using nutritional supplements, standardization of the methodology for the development questionnaires to be necessary and proposing the classification of the Australian Institute of Sport as a reference. PMID- 26268084 TI - ZEOLITE: "THE MAGIC STONE"; MAIN NUTRITIONAL, ENVIRONMENTAL, EXPERIMENTAL AND CLINICAL FIELDS OF APPLICATION. AB - INTRODUCTION: zeolites (clinoptilolites) are a family of alluminosilicates and cations clustered to form macro aggregates by small individual cavities. In the medical area they are involved in detoxification mechanisms capturing ions and molecules into their holes. Actually, we classify about 140 types of natural and 150 synthetic zeolites, for specific and selective use. Clinoptilolite is a natural zeolite and it is the most widespread compound in the medical market. OBJECTIVE: this review analyzes the main fields of zeolite utilization. METHODS: we searched Pubmed/Medline using the terms "zeolite" and "clinoptilolite". RESULTS AND DISCUSSION: in zoothechnology and veterinary medicine zeolite improves the pets' fitness, removes radioactive elements, aflatoxines and poisons. Zeolite displays also antioxidant, whitening, hemostatic and anti diarrhoic properties, projected in human care. However very scanty clinical studies have been run up to now in immunodeficiency, oncology after chemotherapy and radiotherapy as adjuvants. CONCLUSIONS: further clinical investigations are urgently required after this review article publication which updates the state of the art. PMID- 26268085 TI - [DESIGN AND VALIDATION OF AN IMAGE FOR DISSEMINATION AND IMPLEMENTATION OF CHILEAN DIETARY GUIDELINES]. AB - INTRODUCTION: Food-Based Dietary Guidelines (FBDG) are usually accompanied by an image for dissemination and implementation. OBJECTIVE: to design and validate an image to represent the variety and proportions of the new Chilean dietary guidelines, include foods high in critical nutrients that should be avoided and physical activity guidelines. METHOD: a panel of experts tested seven graphics and selected three that were validated with 12 focus groups of people aged 10-14 and 20-40 years, of both sexes, from different socioeconomic groups and from both rural and urban areas. We analyzed the perception of variety and proportions of the food groups for daily intake and motivation for action in diet and physical activity. We utilized the METAPLAN method used previously in the validation of FBDG. RESULTS AND DISCUSSION: the final image was a circle that showed the variety and proportions of each food group for daily consumption (in pictures), included physical activity guidelines in a strip around the middle of the circle and a rectangle towards of bottom of the image with examples of foods high in critical nutrients in black and white. The chosen picture was modified using input from participants and validated with three additional focus groups, improving its understanding and acceptance. CONCLUSION: most participants understood that the image represented the relationship between healthy eating and daily physical activity, correctly identifying the food groups for which increased intake was suggested and those groups in which intake should be reduced or avoided. PMID- 26268086 TI - [DAILY AND ABNORMAL EATING BEHAVIORS IN A COMMUNITY SAMPLE OF CHILEAN ADULTS]. AB - AIMS: this research aimed to characterize the daily eating behavior in a sample of Chilean adults according to their Body Mass Index (BMI) and gender and to analyze the possible links between these variables and abnormal eating behaviors. METHODS: 657 participants (437 women and 220 men, age range 18-64 years) were evaluated with a battery of self-administered questionnaires. Mean BMI was 25.50 kg/m2 (women 24.96 kg/m2, men 26.58 kg/m2), being significantly higher the mean of BMI in the men group, being the BMI mean of the total sample and that of the male group in the overweight range. RESULTS: participants with overweight (BMI >= 25 kg/m2), in contrast with normal-weight group, tended to do more frequently the following behaviors: skip meals, follow a diet, eat less homemade food, eat faster and in greater quantities, in addition to do a greater number of abnormal eating behaviors of various kinds and to rate significantly higher in clinical scales that evaluated eating restraint and overeating. Men showed significantly more eating behaviors linked with overeating, and women performed more behaviors related with eating restraint and emotional eating. DISCUSSION: the results suggest that, besides "what" people eat, "how" people eat, in terms of specific behaviors, may contribute to the rapid increase of overweight in Chilean population. PMID- 26268087 TI - HELICOBACTER PYLORI (HP) INFECTION IN OBESE PATIENTS UNDERGOING ROUXEN- Y GASTRIC BYPASS; EFFICACY OF TWO DIFFERENT TREATMENT REGIMENS IN HP ERADICATION. AB - INTRODUCTION: the ultimate cause for the increased incidence of gastric ulcer following Roux-en-Y gastric bypass (RYGB) remains unclear. Treatment of HP infection is recommended before surgery in countries with high prevalence such as Spain in other to diminish the risk. However, the current regimens used might not be adequate in view of the high failure rate for HP eradication. METHODS: we reviewed 243 patients retrospectively undergoing RYGB and found 111 patients (45%) with HP infection. Therefore, we compared the eradication rate between 2 different regimens. RESULTS: 70 patients received OCA(Omeprazole:20 mg/12h, Clarithromycin 500 mg/12h and Amoxicillin 1 gram/12h for 10 days) while 41 patients received OLA (Omeprazole 20 mg/12 hours, Levofloxacin 500 mg/12hours and Amoxicillin 1 gram/12h for 10 days) for HP eradication. In 56/70 (80%) patients receiving OCA therapy HP was eradicated compared to 37/41 (91%) receiving OLA as first line therapy (p = 0.283). When used as second line therapy, in 13/14 (92%) patients receiving OLA HP was eradicated. CONCLUSION: clarithromycin resistance remains a matter of concern in this population while OLA seems to be a good alternative therapy for HP eradication, especially when OCA regimen fails. PMID- 26268088 TI - ANALYSIS OF INFORMATION CONTENT AND GENERAL QUALITY OF OBESITY AND EATING DISORDERS WEBSITES. AB - INTRODUCTION: nowadays, the Internet is increasingly used by providers as a source of information for eating disorder health issues. However, health information on the Internet remains unregulated and varies in quality, accuracy and readability. OBJECTIVE: the objective of this study was to determine both general and information quality of eating disorder websites, including obesity websites. METHODS: three key terms (obesity, anorexia and bulimia) were entered into the Google search engine. Websites were assessed using two tests (HonCode certification and Bermudez-Tamayo et al. test) to analyze overall quality, and a third test (DISCERN test) to analyze specifically information quality. RESULTS: there were no significant differences regarding overall quality among the different pathologies studied (p = 0.197), although anorexia websites tended to obtain lower quality scores. Furthermore, all evaluated websites showed significant deficiencies regarding information quality (p = 0.032). Nevertheless, obesity websites showed a significant higher information quality than anorexia websites. DISCUSSION AND CONCLUSION: the overall quality of eating disorders websites is moderate, but the information quality that they contain is fairly poor. Remarkably, anorexia nervosa websites showed both the lower information and general quality, while bulimia websites showed a higher general quality and obesity websites presented the most reliable information. PMID- 26268089 TI - [OVERWEIGHT AND PHYSICAL ACTIVITY PRACTICE ASSOCIATED WITH EATING BEHAVIOR OF BRAZILIAN COLLEGE STUDENTS]. AB - INTRODUCTION: inadequate food intake can compromise the cardiovascular health, which increases the chances of developing a number of diseases. The relation of inadequate intake of food and certain cardiovascular risk factors in young adult populations are not clear. OBJECTIVE: the objective of this study was to investigate the association between eating habits of college students, excess body weight, high blood pressure and regular physical activity. METHODS: cross sectional study was conducted with students from a Brazilian federal university. Were evaluated 1 599 students between 18 and 25 years old. An interview was conducted and included sociodemographic variables and the International Physical Activity Questionnaire (IPAQ). Was evaluated body composition (weight, height, calculate the BMI, and waist circumference (WC)). Eating habits and cardiovascular risk behaviors were evaluated by YRBSS -C (Youth Risk Behavior Surveillance). RESULTS: using the chi-square test was identified association between binge drink, consumption of fruits and consumption of salads / vegetables with regular physical activity. There was also an association between consumption of sweet and savory foods, with BMI and waist circumference high. The Logistic regression showed association between sweets intake (odds = 1.34) and savory foods (odds = 1.39) with high BMI. The analysis also showed an association between candy consumption (odds = 1.33), and savory consumption (odds = 1.74) with waist circumference. There was a relationship between MVPA and the binge drink (odds = 1.23), fruits consumption (1.46), and consumption of salads / vegetables (odds = 1.49). Thus, there was an association between the eating habits of college students with excess body weight as well as with regular physical activity. PMID- 26268090 TI - EFFECTIVENESS OF AN EDUCATIONAL INTERVENTION TO REDUCE THE CONSUMPTION OF HIGH CALORIE FOODS IN PUBLIC SCHOOL CHILDREN IN TERESINA, PIAUI (BRAZIL). AB - INTRODUCTION: there is high prevalence of overweight and poor food habits among adolescents, and these factors contribute to the development of chronic diseases. OBJECTIVE: the aim of this study was to evaluate the effectiveness of an educational intervention designed to reduce the consumption of high-calorie foods in public school children in Teresina, Piaui, Brazil. MATERIALS AND METHODS: quasi-experimental, randomized, quantitative intervention study involving adolescents (n = 126) of both sexes aged 10-14 years. An educational intervention, which involved 9 weekly meetings, was developed. A questionnaire was completed prior and subsequent to the intervention. Associations between variables were examined using a chi-square test (x2). RESULTS AND DISCUSSION: there was a significant reduction in the consumption of soft drinks and processed juices subsequent to the educational intervention (p = 0.007). It has further reduction in weekly consumption of food like meat and sausage (p = 0.072). Adolescents' weekly consumption of fried foods and potato chips also decreased significantly subsequent to the educational intervention (p < 0.001). CONCLUSIONS: the food and nutrition educational program was efficacious in reducing the adolescents' intake of high-calorie food and drinks and contributed to an improvement in the quality of food consumed by the schoolchildren evaluated. PMID- 26268091 TI - PREVALENCE OF METABOLIC SYNDROME AMONG ADOLESCENTS IN A CITY IN THE MEDITERRANEAN AREA: COMPARISON OF TWO DEFINITIONS. AB - BACKGROUND AND OBJECTIVE: there are few studies on the prevalence of metabolic syndrome (MetS) in European adolescent populations, and some have reported a higher prevalence in the Mediterranean basin area. Our objective was to examine the prevalence of MetS in adolescents in a Mediterranean city of Spain, comparing two different definitions of MetS and the associated risk factors. METHODS AND RESULTS: a cross-sectional population-based study was conducted among 379 adolescents aged 12-16.9 years, selected using a random sampling method. Anthropometric measurements and fasting blood samples were obtained. The definitions of MetS used were that of the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATPIII) and that of the International Diabetes Federation (IDF). Kappa coefficient was used to measure the agreement between definitions and a multivariate logistic regression model to determine the associated risk factors. RESULTS: the prevalence of MetS was 5.7% (95%CI 3.33 8.07) according to the NCEP-ATPIII definition and 3.8% (95%CI 1.85-5.75) according to the IDF definition. No differences between the sexes or by age groups were found. The agreement between the two definitions was very good (kappa 0.815), especially in the obese subsample, but was lower in normal weight adolescents (kappa 0.497). Insulin resistance and obesity were associated with both definitions. CONCLUSIONS: the prevalence of MetS in our adolescent population is higher than the European media. Although the overall agreement between both definitions was very good, the prevalence was higher using the NCEP ATPIII criteria. Independently of the definition used, obesity and insulin resistance were risk factors for MetS. PMID- 26268092 TI - INTRODUCTION OF PASTEURIZED/RAW COW'S MILK DURING THE SECOND SEMESTER OF LIFE AS A RISK FACTOR OF TYPE 1 DIABETES MELLITUS IN SCHOOL CHILDREN AND ADOLESCENTS. AB - OBJECTIVE: to demonstrate that type 1 diabetes mellitus (T1DM) in school children and adolescents is associated with the early introduction of pasteurized/raw cow's milk in the second semester of life. MATERIAL AND METHODS: this non probabilistic study included 150 subjects (75 patients and 75 controls), divided according to sex and age (range, 6 to 16 years). T1DM was considered to be a dependent variable, and pasteurized/ raw cow's milk (P/RCM) was considered to be an independent variable in the study. The statistical analyses included chi squared test, odds ratio and 95% confidence intervals. RESULTS: the subjects were 51% male, age 11 +/- 3.2 years, and 80% were breastfed, 18% were exclusively breastfed, and 13% received pasteurized/raw cow's milk. The children receiving P/RCM had a higher risk of T1DM [OR, 3.9 (1.2-12.8)]. The presence of T1DM was three times higher in those consuming P/RCM vs. those receiving follow-up formula [RM, 3.2 (1.03-10.07)]. CONCLUSIONS: introducing pasteurized/raw cow's milk in the second semester of life increased by four times the likelihood of developing T1DM in children and adolescents. PMID- 26268093 TI - IMMUNE RESPONSE OF SEVERE MALNUTRITION CHILDREN TREATED ACCORDING TO THE PROTOCOL OF THE WORLD HEALTH ORGANIZATION. AB - The aim of the study was to compare the innate immune system of severely malnourished children admitted to the Instituto de Medicina Integral Professor Fernando Figueira and treated according to the protocol of the World Health Organization (WHO) at admission and discharge. An experimental study was conducted with 20 children under two years of age. Ten of them had severe malnutrition and ten were a control group. The malnourished group consisted of hospitalized infants and it was submitted to WHO's protocol. Children with HIV and re-admitted during the study period were excluded. A blood sample was taken at admission and at discharge. Later, an analysis of blood leukocytes, adherence index, phagocytic capacity, production of free radicals superoxide and nitric oxide was performed. Patients with severe malnutrition at hospital discharge showed improved phagocytic function, release of oxygen radicals and reduction of the number of lymphocytes when compared to the time of admission. When compared to the control group, patients at hospital discharge had lower lymphocyte values and lower production of free radicals. Thus, it can be concluded that the duration of hospitalization was insufficient to restore cell-mediated immunity and microbicide activity. PMID- 26268094 TI - RELATIONSHIPS AMONG THYROID HORMONES AND OBESITY SEVERITY, METABOLIC SYNDROME AND ITS COMPONENTS IN TURKISH CHILDREN WITH OBESITY. AB - BACKGROUND: we investigated the relationships between thyroid function and obesity severity, metabolic syndrome (MS) and MS components in 260 obese children and adolescents 10-17 years of age. OBJECTIVES: we aimed to determine the association of thyroid functions with obesity severity and the components of metabolic syndrome (MS) in pediatric obese patients. METHODS: only obese children and adolescents were included, and divided the obese children into three groups according to body mass index (BMI)-SDS quartiles. The first quartile was group 1, the second and third quartiles were group 2, and the fourth quartile was group 3. Group 3 indicated severe obesity. The modified WHO criteria adapted for children were used to diagnose MS. We assessed anthropometric data and serum biochemical parameters, including the lipid profile and fasting glucose (FG), insulin, thyroid-stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3) levels. Blood pressure (BP) was measured with a standard digital sphygmomanometer. The homeostasis model assessment of insulin resistance was calculated to determine insulin resistance (IR). RESULTS: TSH level was significantly higher in obese children with MS than that in the others (p = 0.045). Mean TSH level was not different among the BMI-SDS groups (p = 0.590). TSH levels and the fT3/fT4 ratio were not different in children with dyslipidemia, IR or hypertension (p = 0.515, 0.805, 0.973, 0.750, 0.515, and 0.805, respectively). DISCUSSION: obesity severity does not affect TSH level or the fT3/fT4 ratio in obese children and adolescents. IR is in close relationship with TSH level. Elevated TSH level is a risk factor for MS. PMID- 26268095 TI - [HEPATOTOXICITY FROM THE CONSUMPTION OF HERBALIST PRODUCTS BY A PAEDIATRIC POPULATION]. AB - The consumption of herbal products is mainly due to the perception that being "natural" can only be beneficial and without risk to health. However the properties thereof are poorly studied and proven. Four episodes are presented of hepatotoxicity from the consumption of herbal products, by three children. We analyse the epidemiological and clinical characteristics of these products, and stress the importance of proper anamnesis for accurate diagnosis. PMID- 26268096 TI - METABOLIC SYNDROME AND ITS COMPONENTS IN SPANISH POSTMENOPAUSAL WOMEN. AB - OBJECTIVES: this study aimed to estimate prevalence of metabolic syndrome and all its components to know the cardiovascular risk and metabolic control of the main risk factors in postmenopausal women aged over 45 years in the province of Cuenca (Castilla-La Mancha, Spain). METHODS: in this cross-sectional study, we randomly selected 716 postmenopausal women from 3,108 women aged over 45. Metabolic syndrome was identified according to the National Cholesterol Education Program Adult Treatment Panel III definition. Cardiovascular risk was calculated by the Systematic Coronary Risk Evaluation ( < 65 years). The American Diabetes Association's standards of medical care in diabetes were used to estimate metabolic control. The statistical analysis was done with SPPS.19 RESULTS: prevalence of metabolic syndrome was 61.7% (95%CI: 56.9-66.4). Prevalence of each component was: high blood pressure: 95.8% (95%CI: 95.7-95.8), abdominal obesity: 91% (95%CI: 90.9-91.0), low high-density lipoproteins cholesterol (HDLc) levels: 70% (95%CI: 69.8-69.9), high triglyceride levels: 56.9% (95%CI: 56.4- 56.9), high glucose levels: 54.3% (95%CI: 54.2-54.3). Cardiovascular risk was moderate until 65 years, but was high after this age. Metabolic control in postmenopausal women was very good for glucose, bad for systolic blood pressure and worse for lipid levels. Bad blood pressure control was associated with being over 65 years, being hypertensive and taking treatment for diabetes, but it reduced when being physically limited to do moderate exercise and anxiety increased. CONCLUSIONS: prevalence of metabolic syndrome in postmenopausal women in the province of Cuenca is the highest in Spain. High blood pressure and abdominal obesity are the commonest components. Cardiovascular risk was moderate-high in postmenopausal women, but systolic blood pressure and lipid profile were unsatisfactorily controlled. Early intervention is necessary to achieve a better risk profile. PMID- 26268097 TI - EVALUATION OF SEVERAL ANTHROPOMETRIC INDICES OF OBESITY AS PREDICTORS OF METABOLIC SYNDROME IN JORDANIAN ADULTS. AB - INTRODUCTION: anthropometric indices have all been tested for their relation to metabolic syndrome (MetS), but with no consistent cut-off points are yet established among different population group. OBJECTIVE: this study aims to evaluate the predictive power of several anthropometric indices of central obesity as predictors of MetS in a group of Jordanian adults. METHODS: in this cross sectional study, 630 adult subjects (308 men and 322 women) aged between 20 70 years were recruited at the King Hussein Medical Center in Amman (Jordan). The diagnosis of MetS was defined by the International Diabetes Federation criteria. Anthropometric measurements (waist circumference [WC]; waist to hip ratio [WHpR]; waist to height ratio [WHtR]; body mass index [BMI]) were performed and recorded following standard procedures. Receiver operating characteristic (ROC) curves were used to determine the efficacy of anthropometric measurements as predictors of MetS. RESULTS: the results indicated that, in men for identifying subjects with MetS risk, area under curve (AUC) from the ROC curves for WC was 0.851, AUC for WHpR was 0.842, AUC for WHtR was 0.85, and AUC for BMI was 0.83. In women, AUC for WC, WHpR, WHtR, and BMI were 0.866, 0.871, 0.872, and 0.831, respectively. CONCLUSION: it could be concluded that among anthropometric indices, both WHtR and WC had the strongest predictive power for identifying subjects with MetS in men and women. WHtR appears to be the best indicator of central obesity in women and individuals of short stature. PMID- 26268098 TI - URINARY LOSS OF MICRONUTRIENTS IN DIABETIC PATIENTS ATTENDING A TERTIARY HOSPITAL SERVICE. AB - BACKGROUND/AIMS: micronutrient deficiency may contribute to a poorer control of diabetes. Thus, the objective of the present study was to assess the urinary excretion of micronutrients in patients with type 2 diabetes mellitus. METHODS: patients with diabetes and controls were assessed regarding food intake, anthropometry, urinary loss of micronutrients and compared by the nonparametric Mann-Whitney test (p < 0.05). RESULTS: nine diabetic volunteers (52 +/- 14 years, BMI 30 +/- 11 kg/m2 and abdominal circumference (AC) of 99 +/- 25 cm) and 9 control individuals (51 +/- 16 years, BMI 26 +/- 5 kg/m2 and AC of 90 +/- 13 cm) were studied. Higher iron excretion was observed in the diabetic group and higher magnesium excretion in the control group. CONCLUSIONS: the type 2 diabetic patients here studied did not show increased micronutrient excretion in urine when compared to controls. PMID- 26268099 TI - [INFLUENCE OF THE NUTRITIONAL COMPOSITION OF DIFFERENT FIBER-ENRICHED ENTERAL NUTRITION FORMULAS ON THE ADMINISTRATION TIME BY GRAVITY AND THE RISK OF TUBE FEEDING OBSTRUCTION]. AB - INTRODUCTION: the administration of enteral nutrition by gravity is a very useful method in clinical practice; nevertheless, it may not be very precise. Indeed, this method presents some important limitations, such as the difficulty in establishing a precise dripping rate and the possibility for the dripping rate decrease depending on the formula. OBJECTIVES: assess the administration time and the risk of clogging of 5 fiber-enriched enteral nutrition formulas with different protein concentrations and caloric density, all administered by gravity through nasogastric (NG) tubes of different sizes. Assess the influence of the composition on the dripping rate, by gravity, of the tested formulas. METHODS: 5 fiber-enriched EN formulas were compared by using nasogastric tubes of the calibers 8, 10 and 12 Fr. The fluidity of these gravity-administered NE formulas was estimated by timing the complete passage of each formula at full speed, thus allowing one to calculate the mean time of free fall (MTFF) and to register any possible obstruction. Subsequently, an in vitro simulation of a 1 500 ml administration was performed for each formula at a particular speed, so that the administration time was 5 hours. Slowing flow and stagnated flow were detected as indicators of the risk of obstruction. RESULTS: the two products that especially differed in MTFF were the ones with the highest energy concentration. The passage time in free fall of these two products through the 8 Fr tube exceeded four hours. For the rest of the products and NG tubes used, this time was less than 2 hours and 5 minutes. No slowing flow or tube obstruction was detected in free fall and at maximum speed. When the dripping was adjusted to be administered in 5 hours, three of the studied products (those with the least caloric concentration and viscosity) showed slowing flow and, in some cases, the dripping stopped completely. The most important factor associated to the MTFF was the lipid content, followed by viscosity, energy and protein content. The MTFF measured was not significantly related to the fiber content of the nutritional formula. CONCLUSIONS: all studied products can be administered by gravity via nasogastric tubes in free fall without any risk of obstruction, even though the free fall time was very variable. The lowest caliber tubes, the highest energy content and the viscosity of the EN mixture turn-out to be the limiting factors when fiber enriched formulas are to be administered by gravity. PMID- 26268100 TI - TRAQUEOESOPHAGEAL FISTULA PATIENTS FED THROUGH PERCUTANEOUS ENDOSCOPIC GASTROSTOMY/GASTROJEJUNOSTOMY: NUTRITIONAL STATUS AND CLINICAL OUTCOME. AB - BACKGROUND: tracheoesophageal fistula (TEF) may result from cancer or mechanical ventilation. Endoscopic Gastrostomy or Gastrojejunostomy (PEG/PEG-J) is used for nutritional support. OBJECTIVE: in TEF-patients, evaluating nutritional status when PEG is performed, safety of PEG/PEG-J and clinical outcome. METHODS: from the files of PEG/PEG-J feed TEF-patients we collected: clinical data, Body Mass Index, albumin, transferrin and cholesterol when gastrostomy was performed, and clinical outcome globally and according with the TEF cause: Group 1: complication of mechanical ventilation, Group 2: cancer. RESULTS: twelve patients, 18-91 years (median: 53), 11 PEG, one PEG-J: six complications of ventilation (neurological diseases), 6 cancers. Mean period from TEF diagnosis until gastrostomy: 2 months in Group 1, 10 months in Group 2. In the day of the gastrostomy, patients presented with malnutrition parameters, most strikingly in the cancer group. Group 1: died a single patient, 3 closed the TEF, resuming oral intake, 2 are still PEG-feed. All cancer patients died (7 months after gastrostomy). One needed a jejunal extension to create a PEG-J. No more complications. CONCLUSION: PEG/PEG J was safe in TEF-patients, but cancer patients underwent gastrostomy too late. In TEF-patients, PEG/PEG-J should be considered in a regular basis, earlier in the disease evolution, before established malnutrition. PMID- 26268101 TI - THE ACTION OF AVOCADO OIL ON THE LIPIDOGRAM OF WISTAR RATS SUBMITTED TO PROLONGED ANDROGENIC STIMULUM. AB - INTRODUCTION: the abuse of steroid hormones administered in chronic form may cause alterations in the lypidic profile, conveying na increase in the levels of LDL, and reduction in the levels of HDL. In average, 53.44% of the lypidic composition of the avocado core is composed of oleic acid (which is a phytosterol) and the study of the hypolipemiating effect of these substances has been performed aiming at the prevention and control of dislypidemias. OBJECTIVE: to assess the potential hypolipemiant power of the avocado oil on the lypidogram of adult male Wistar rats submitted to prolonged androgenic hiperestimulation. MATERIALS AND METHODS: twenty eight Wistar rats were divided in 4 groups of 7 animals: the control group (CG); Avocado Oil Group (AOG) fed with a staple based on Avocado Oil; Induced Grupo (IG); and the Induced Grupo fed with a staple based on Avocado Oil (AOIG). The inducing was performed through surgery to subcutaneously implant sillicon pellets suffed with 1 ml of testosterone propionate which were replaced at every 4 weeks. RESULTS: VLDL (AOIG: 28.14 +/- 4.45; IG:36.83 +/- 5.56 mg/ml); Triglicerides (AOIG: 140.07 +/- 22.66; IG: 187.2 +/- 27 mg/ml); HDL (AOIG: 40, 67 +/- 1.2; GI: 35.09 +/- 0.8; AOG: 32.31 +/- 2.61 e CG: 32.36 +/- 4.93 mg/ml) Testosterone (AOIG:1.42 +/- 0.46; GI: 2.14 +/- 0.88; AOG: 2.97 +/- 1.34 e CG:1.86 +/- 0.79 ng/ml). CONCLUSION: avocado Oil exerted a direct regulating effect on the lypidic profile, acting efficiently on animals submmited to androgenic stimulation through a prolonged period. PMID- 26268102 TI - CHEMICAL COMPOSITION, CHARACTERIZATION OF ANTHOCYANINS AND ANTIOXIDANT POTENTIAL OF EUTERPE EDULIS FRUITS: APPLICABILITY ON GENETIC DYSLIPIDEMIA AND HEPATIC STEATOSIS IN MICE. AB - The significance of polyphenol intake for the prevention of chronic diseases is controversial. OBJECTIVE: this study investigated the chemical composition and antioxidant potential of an anthocyanin-rich extract from Euterpe edulis fruits (LPEF) and its effects on liver steatosis in dyslipidemic apoE-/- knockout mice. MATERIALS AND METHODS: mice were divided into G1 (C57BL/6) standard diet; G2 (apoE-/-) standard diet, G3 (apoE-/-) 2% LPEF, G4 (apoE-/-) 6% LPEF, G5 (apoE-/-) 10% LPEF, G6 (apoE-/-) 2% alpha-tocopherol acetate. After 75 days of treatment, the animals were euthanized. The LPEF contained a high level of monomeric anthocyanins (301.4 mg/100g) and marked antioxidant activity. RESULTS: Catalase activity was reduced in G3, G4, G5 and G6 compared to G2. Superoxide dismutase was reduced only in G4. The animals in G4, G5, and G6 showed low HDL and triglycerides levels compared to G2. The proportion of lipid droplets in liver tissue was reduced in G4 and G5 compared to G2, G3, and G6. CONCLUSION: The results indicated that E. edulis pulp is rich in anthocyanins and the LPEF dietary consumption can reduce the severity of liver steatosis in apoE-/- mice, an effect that is potentially mediated by the antioxidant activity of this extract and modulation of triglyceride serum levels. PMID- 26268103 TI - IMPACT OF IMPROVED FAT-MEAT PRODUCTS CONSUMPTION ON ANTHROPOMETRIC MARKERS AND NUTRIENT INTAKES OF MALE VOLUNTEERS AT INCREASED CARDIOVASCULAR RISK. AB - INTRODUCTION: meat products have been recognized to be adequate matrix for incorporating functional ingredients. The impact of meat products formulated by replacing animal fat with a combination of olive, linseed and fish oils on energy and nutrient intakes and anthropometric measurements were tested in a non randomized-controlled- sequential study. METHODS: eighteen male volunteers at high-CVD risk consumed weekly 200 g frankfurters and 250 g pates during three 4 wk periods (reduced fat (RF); n3-enriched- RF (n-3RF), and normal fat (NF)), separated by 4-wk washout. Energy and nutrient intakes, healthy eating index (HEI), and anthropometric changes were evaluated. RESULTS: body fat mass rate-of change and the waist/ hip ratio significantly differs (p = 0.018 and p = 0.031, respectively) between periods, decreasing body fat mass, waist circumference and waist/hip ratio in RF period and increasing body fat mass in NF one (all p = 0.05). Significant inverse correlations were observed between rate- of-change of BMI and ideal body weight with dietary carbohydrate/SFA ratio in n-3RF period (p = 0.003 and p = 0.006, respectively). Initial diets presented low HEIs (means < 60). Carbohydrate, fat and protein energy contribution was 40%, 41%, and 16%, respectively. More than 33% of volunteers did not initially cover 70% of several minerals and vitamins RDAs. Product consumption improved dietary Zn, Ca, retinol equivalent, folate and vitamin B12 contents in all periods, and ameliorated n-3 PUFA contents and n-6/n-3 PUFA ratio over the n-3RF period. CONCLUSION: improved fat meat products appear as functional foods for overweight/obeses since their consumption improved selected body-fat markers, without affecting HEI, macronutrient and energy but their n-3 PUFA and n6/n3 ratio intakes. PMID- 26268104 TI - EFFECTS OF A DIETARY SUPPLEMENT ON THE INCIDENCE OF ACUTE RESPIRATORY INFECTIONS IN SUSCEPTIBLE ADULTS: A RANDOMIZED CONTROLLED TRIAL. AB - INTRODUCTION: although supplementation of specific micronutrients may improve immunologic factors, few studies about the combination of micronutrients with plant extracts on the occurrence of acute respiratory infections (ARI) have been published. OBJECTIVES: to assess the effect of a nutritional supplement with micronutrients and plant extracts on the incidence of ARI in susceptible adults between January and April, 2012. METHODS: a randomized, double-blind, parallel, placebo- controlled clinical trial was performed. Participants were adults susceptible to ARI who were healthy at the time of evaluation, signed informed consent forms and were not taking medication. They completed a medical history; weight, height, vital signs and laboratory analyses were assessed. Subjects were randomly assigned for consumption of the supplement or a placebo, for a 90 days period. Subjects made daily diary entries indicating the presence ARI symptoms. Those who became ill notified researchers and the attending physician confirmed the presence of an infection. Fisher's exact test was used to compare the proportion of ill subjects between groups. Relative risk and risk difference were also calculated (p < 0.05 significant). RESULTS: of 59 included subjects, 45 (25 women) completed the study (21 in the supplemented group and 24 in the placebo group). There were no significant differences at baseline between groups. After the intervention, the supplemented group had a lower incidence of ARI compared with the placebo group (57.1% vs. 91.7%, p = 0.013, RR = 0.62, 95%CI 0.42, 0.92). DISCUSSION: the consumption of a supplement with vitamins, minerals and plant extracts may decrease the incidence of ARI in susceptible adults. PMID- 26268105 TI - STUDY OF ACAROID MITES POLLUTION IN STORED FRUIT-DERIVED CHINESE MEDICINAL MATERIALS. AB - OBJECTIVE: to investigate the species and breeding density of acaroid mites in stored fruit-derived Chinese medicinal materials in Anhui province. METHODS: samples of stored fruit-derived Chinese medicinal materials were collected from 30 herb stores and storehouses in 17 Anhui cities, where the breeding acaroids mites were detected. RESULTS: 20 species of acaroids mites were found in 33 samples, belonging to 15 genus, 5 families of the acaridae respectively, among which T. putrescentiae, A. farinae, C. lactis, and C. berlesei are predominant species. CONCLUSION: stored fruit-derived Chinese medicinal materials in Anhui areas suffer from serious acaroid mites pollution. Therefore, proactive measures should be taken to control acaroid mites from breeding in an effort to reduce the harm on medicinal materials. PMID- 26268106 TI - TRANS FATTY ACIDS MODIFY NUTRITIONAL PARAMETERS AND TRIACYLGLYCEROL METABOLISM IN RATS: DIFFERENTIAL EFFECTS AT RECOMMENDED AND HIGH-FAT LEVELS. AB - INTRODUCTION: there is still little evidence on the metabolic trans fatty acids (TFA) effects at recommended fat levels. OBJECTIVE: to investigate the differential TFA effects on some nutritional parameters, TFA retention, and triacylglycerol (TAG) regulation in rats fed recommended and high-fat diets. METHODS: male Wistar rats were fed (30 days) diets containing recommended (7%,w/w) or high-fat (20%,w/w) levels, supplemented or not with TFA (C7, C20, TFA7 and TFA20). RESULTS: TFA7 (vs.C7) rats showed an increased body weight associated with higher fat pads and liver and serum TAG. The hypertriacylglyceridaemia was related to a decreased muscle LPL activity, while the higher hepatic TAG content was associated with both an increased SREBP-1c gene expression and ACC activity, and a reduced CPT-Ia gene expression. The TFA20 diet did not potentiate the higher body weight, fat pads and TAG levels induced by the C20 diet. Although the hepatic TAG-secretion rate (TAG-SR) increased by TFA20 vs. C20, the same triacylglyceridaemia was associated with a compensatory increase of the adipose tissue LPL activity. The attenuated hepatic TAG accretion in TFA20 was related to an increase of TAG-SR and to a lower increase of SREBP-1c and SCD1 mRNA expressions, paralleled to a relative decrease of SCD1 index and ACC activity. DISCUSSION AND CONCLUSION: TFA alters nutritional parameters and lipid metabolism in rats. However, different responses to the TFA on TAG levels and their regulation were observed between rats fed recommended and high-fat diets. These divergences might be related to different tissue TFA retentions and rumenic acid bioconversion. PMID- 26268107 TI - EFFECT OF LONG TERM INTAKE OF WHITE TEA ON ACUTE OXIDATIVE STRESS IN RATS. AB - INTRODUCTION: the well known antioxidant properties of white tea include the prevention of cancer, neurodegenerative diseases and oxidative stress. Adriamycin can generate an amount of oxidative stress in vivo. OBJECTIVE: evaluate long term intake of white tea on plasma antioxidant capacity and on the fatty acid profile of liver and heart microsomes in animals subjected to acute oxidative stress. METHODS: rats were given distilled water (controls), 15 mg/d (dose 1) or 45 mg/d (dose 2) of solid white tea extract/per kilogram of body weight for 12 months. After this time, all the animals received an injection of adriamycin (ADR) (10 mg/kg body weight), except half of the control group, which were given an injection of saline solution. Samples of plasma and liver and heart were taken. The antioxidant activity, the carbonyl groups and hydroperoxide concentration were analyzed in plasma, and the fatty acid profiles of liver and heart microsomes were obtained. RESULTS & DISCUSSION: only the hydroperoxides showed significant changes, while slight tendencies were observed in antioxidant activity and the carbonyl groups. Although the long term intake of white tea and the administration of adriamycin did not change the fatty acid profile, slight tendencies existed for the SFAs, MUFAs and PUFAs. PMID- 26268108 TI - ANTHROPOMETRIC DIFFERENCES RELATED TO GENDERS AND AGE IN THE ELDERLY. AB - INTRODUCTION: anthropometry facilitates the evaluation of the risks associated with reduced lean body mass, as well as of excess adiposity. However, very little is known regarding the anthropometric standards among the elderly and the differences observed between the genders and among the various age groups Objective: to compare indicators and indices anthropometrics of the elderly by gender and age group. METHODS: a cross-sectional study was undertaken using a representative probability sample, involving 621 elderly. We evaluated the weight, height, circumferences (waist, hip, calf and arm); body mass index, body adiposity index, waist-hip ratio and waist-stature ratio. RESULTS: women were found to have a higher mean body mass index, waist-stature ratio, body adiposity index and arm circumference (p < 0.001), whereas men had higher values for weight, height and waist-hip ratio (p < 0.001). The average arm and calf circumference, however, did not differ between the genders (p > 0.05). Weight, and calf and arm circumferences were observed to be lower in the older age groups (p < 0.001) and the same was true for the body mass index and height only in men (p < 0.05). The waist circumference, waist-hip ratio, body adiposity index and waist-stature ratio did not differ among the age groups (p > 0.05). CONCLUSION: the total and peripheral body mass, for the men, in particular, was lower among the older subjects. Central adiposity did not differ among the age groups in both the genders. PMID- 26268109 TI - [ANTHROPOMETRIC PARAMETERS' CUT-OFF POINTS FOR DIAGNOSIS OF SARCOPENIA]. AB - INTRODUCTION: sarcopenia is a syndrome characterized by loss of muscle mass associated with reduced muscle strength and/or reduced functional capacity. The ageing of our population is producing an increase of the prevalence related with age in addition to other factors related to malnutrition and certain diseases. The aim of this study was to provide a tool for diagnosing sarcopenia while determining in an accessible way the loss of muscle mass. MATERIAL AND METHODS: an anthropometric standardized protocol was completed on 883 men and 506 women, healthy and active, aged 20-39 years. The following muscular development indices were calculated: body circumferences (upper arm, forearm, thigh, and calf) corrected circumferences (upper arm, thigh and calf), cross-sectional area (CSA, upper arm, thigh, and calf) and whole- body muscle mass (kg), and as a percentage (%) and in relation to height (kg/m2) by Lee's equation. The cutoff point was established as the 2.5 percentile (lower endpoint of the 95% confidence interval) for the analyzed studied. RESULTS: significant differences by gender (p < 0.0001) were found in all the indicators analyzed. The cut-off points of the loss of skeletal muscle mass were 9,1 kg/m2 in men; and 7.3 kg/m2 in women. And in the CSA (cm2), men vs. women: upper arm, 37.7 vs. 24.2; , thigh, 154.3 vs. 115.8; and calf, 78.8 vs. 60.2. CONCLUSIONS: there is sexual dimorphism which requires considering differentiated diagnostic criteria. The anthropometric technique can serve as screening method for sarcopenia on the study of large populations. PMID- 26268110 TI - LIPID PROFILE AND ASSOCIATED FACTORS AMONG ELDERLY PEOPLE, ATTENDED AT THE FAMILY HEALTH STRATEGY, VICOSA/MG. AB - BACKGROUND: the aging population has been accompanied by epidemiological changes of the Brazilian population, with the highlight being the continued growth of the prevalence of non-communicable chronic diseases especially cardiovascular or artery-coronary, resulting from changes in the lipid profile of the elderly. OBJECTIVE: this study had the aim to describe the behavioral, anthropometric, lifestyle and body composition factors and their association with changes in the lipid profile of elderly people. METHODOLOGY: the sample included 402 participants attended at the Family Health Strategy, Vicosa (MG), to which a questionnaire with socio-demographic, behavioral and lifestyle information was applied. Blood sample was collected to obtain the lipid fractions, and the weight, height, waist circumference and body fat percentage were measured. Multiple linear regression was performed to identify independently associated factors with changes in each of the selected lipid fractions. RESULTS: the factors independently associated with increased levels of total cholesterol were the presence of sedentary behavior, high body fat percentage, greater waist height and greater waist circumference. The consumption of alcoholic beverages and a higher waist-hip ratio remained independently associated with decreased high-density lipoprotein levels. The increased waist circumference was independently associated with low values of the low-density lipoprotein levels. The value of increased triglyceride was independently associated with higher waist-hip ratio, higher body mass index and smoking. CONCLUSIONS: modifiable risk factors associated with a changed lipid profile should be prioritized among the actions to be considered in structuring health programs for the elderly. PMID- 26268111 TI - EVALUATION OF DIET ACCEPTANCE BY PATIENTS WITH HAEMATOLOGICAL CANCER DURING CHEMOTHERAPEUTIC TREATMENT. AB - INTRODUCTION: a compromised nutritional status is one of the factors that may increase the morbidity and mortality of chemotherapy patients. The goal of this study was to evaluate acceptance of the diet by patients with haematological cancer throughout their hospital stay for chemotherapeutic treatment. METHOD: this was a cross-sectional, descriptive, quantitative study, carried out from February to October 2014 in adult patients of both genders diagnosed with lymphoma and leukaemia. Food intake was evaluated on a daily basis through a recording instrument designed by the author. ANOVA test for repeated measurements was employed. RESULTS: 32 patients were evaluated, with a mean age of 42 +/- 11 years, the majority of whom were women (66%). We observed gastrointestinal disturbances in 72% of the patients, most commonly nausea (59%), followed by xerostomia (34%), vomiting (28%) and dysgeusia (25%). The percentage of leftover food was significant, varying from 23% to 35%. Lunch and dinner were the most frequently rejected meals. Light meals were more well-tolerated, having been accepted in 75% to 100% of the offers. CONCLUSION: The food records show that during chemotherapy cycles, patients present significant food rejection, specially with larger meals such as lunch and dinner, though light meals are better tolerated. Employing food options chosen by patients may be a strategy to improve dietary acceptance. More studies on this subject are necessary in order to improve nutritional care to this population, aiming to prevent and/or rehabilitate the nutritional status of these patients. PMID- 26268112 TI - RELATIONSHIP BETWEEN ZINCEMIA, SUPEROXIDE DISMUTASE ACTIVITY AND MARKER OF OXIDATIVE STRESS IN WOMEN WITH BREAST CANCER. AB - INTRODUCTION: studies show changes in zinc metabolism in women with breast cancer. This mineral has antioxidant action, and disorders in its biochemical parameters are related to poor prognosis of the disease and increase in the carcinogenic process. OBJECTIVE: this study evaluated the activity of enzyme superoxide dismutase and biochemical parameters related to zinc, and investigated the existence of correlation between these variables and the marker of oxidative stress in these patients. METHODS: this was a case-control study with 66 women aged between 20 and 50 years old, distributed into: case group (women with breast cancer, n = 34) and control group (healthy women, n = 32). Zinc intake was analyzed by three-day food diary, using Nutwin software, version 1.5. Plasma and erythrocyte zinc concentrations were determined by flame atomic absorption spectrophotometry method (lambda = 213.9). Superoxide dismutase activity was assessed by Griess colorimetric method, and plasma thiobarbituric acid reactive substances (TBARS) were analyzed. RESULTS AND DISCUSSION: mean levels of zinc intake, superoxide dismutase and TBARS were higher than recommended for the study participants with statistical difference for enzyme superoxide dismutase (p < 0.05). Mean plasma and erythrocyte concentrations of zinc were reduced in both groups (p > 0.05). CONCLUSIONS: therefore, it can be assumed that zinc intake in women with breast cancer does not impact plasma and erythrocyte concentrations of this mineral. High superoxide dismutase activity in women with breast cancer may be due to a compensatory mechanism of regulation via oxidative stress found in this disease. PMID- 26268113 TI - POSITIVE EFFECTS OF RESISTANCE TRAINING ON INFLAMMATORY PARAMETERS IN MEN WITH METABOLIC SYNDROME RISK FACTORS. AB - BACKGROUND: evidences have shown a strongly association between metabolic syndrome (MS), cardiovascular diseases and chronic low-grade inflammation, being this last, related with the occurrence of sarcopenia and atherosclerosis. Despite several benefits, the effects of resistance training (RT) on inflammatory profile are controversial. Thereby, this study aims to investigate the effects of a RT on the inflammatory profile of men with MS risk factors. METHODS: fifteen sedentary men (57.53 +/- 7.07 years old) with 2 or more MS components underwent a RT for 14 weeks (3 times per week), with intensity ranging between 40 and 70% of one repetition maximum. The dual-energy X-ray absorptiometry was used to body composition assessment and serum was collected to evaluate biochemical and inflammatory parameters before and after the RT. RESULTS: despite the absence of changes in body weight, total muscular content and biochemical parameters, the individuals demonstrated a reduction on body fat content (p < 0.05). Furthermore, the RT resulted in lower circulating levels of tumor necrosis factor alpha and interleukin- 6 (p < 0.05), in higher levels of intelerukin-10 (p < 0.05) and in the stabilization of interleukin-1 beta and interferon-gamma concentrations. It was concluded that a moderate RT benefits inflammatory profile, contributing to a lower risk of cardiovascular diseases. PMID- 26268114 TI - [BODY COMPOSITION AND SOMATOTYPE IN UNIVERSITY TRIATHLETES]. AB - INTRODUCTION: the triathlon is an endurance sport and individual that consists of three different disciplines: swimming, cycling and running. The aim of the study was to describe and analyze the anthropometric characteristics, body composition and somatotype in male college triathletes. METHODOLOGY: observational and descriptive study of anthropometric characteristics, body composition and somatotype of 39 male college athletes from 24 +/- 4,5 years, participants in the championship of Spain university triathlon sprint mode (Alicante 2010), from different universities Spanish. According to anthropometric measurement techniques adopted by the International Society for the Advancement of Kinanthropometry (ISAK) and the Spanish Group Cineantropometria (GREC) by an accredited assessor ISAK Level II. RESULTS: we find athletes of stunting, where you destacanvalores below normal in the subscapularis, supraspinatus, triceps and biceps skinfold, percentage of muscle mass (45.27 +/- 3.29%) and fat mass (10.22 +/- 2.92%) and bone (16.65 +/- 1.34%) and where mesomorphy somatotipo predominates. DISCUSSION: the triathletes and runners have lower size that cyclists and swimmers. Triathletes and cyclists show a similar weight, less than swimmers line, and more than 10km runners. Iliac crest skinfold, abdominal and thigh front cyclists are less than triathletes. The percentage of fat mass of runners triathletes and swimmers are similar, however the muscle mass of athletes usually less than cyclists but similar to other forms. Somatotype resembles triathlete cyclist (mesomorph). The corridor is ectomorph and mesomorph-swimmer can range from a ectomorph mesomorph. PMID- 26268115 TI - [TOBACCO CONSUMPTION AMONG ADULTS IN MONTERREY: RELATION TO EXERCISE REGULARLY AND FAMILY]. AB - OBJECTIVE: determine the relationship among tobacco consumption, physical activity, sociodemographic variables and family behaviours in Mexican adults. METHODS: 978 Mexican adults (483 males and 495 females) were interviewed by a random routes questionnaire. Multinomial logistic regression was used to calculate odds ratio (OR) and confidence interval (CI = 95%). RESULTS: men have a high risk factor of tobacco comsumption in frequency and/or amount. 18 to 45 years-old is the age range with high probability of tobacco comsumption, while the more age, the less comsumption. The tobacco consumption risk is significantly low in people who have less that a primary education. Participants who have never done physical exercise have a low possibility of tobacco consumption, while the consumption is high in the group of people who have abandoned physical activity. The family context is a risk factor of tobacco consumption in frequency. About alcohol consumption, it was found that people who drink alcohol have a high probability of smoke. CONCLUSIONS: tobacco consumption at high frequencies and amounts and physical activity are inversely relationship. It has been also detected a direct relationship between the frequency and the amount of tobacco and alcohol consumptions; and between the frequency and the amount of tobacco consumption and the family in the tobacco consumption. PMID- 26268116 TI - ANTHROPOMETRIC PROFILE AND NUTRITIONAL INTAKE IN PATIENTS WITH EPILEPSY. AB - BACKGROUND: quality of life impairments are common in patients with epilepsy, especially due to cardiovascular comorbidities, overweight and obesity. OBJECTIVES: to evaluate the nutritional status of patients with epilepsy based on anthropometric measurements and dietary intake. METHODS: this cross-sectional study involved 72 patients recruited by convenience from the Epilepsy Clinic of the Clinical Hospital of Porto Alegre, Brazil. The sample consisted of patients of both genders, aged over 18 years, who had been diagnosed with epilepsy for at least one year. The following variables were investigated: anthropometric measurements (weight and height for the assessment of BMI and nutritional status, waist circumference for the assessment of cardiovascular risk); nutritional intake based on a food frequency questionnaire; socioeconomic status based on the Brazilian Economic Classification Criteria. RESULTS: the prevalence of overweight/obesity was 66.7%, and 85.4% of the women had a high cardiovascular risk. Patients displayed a low frequency of seizure control (41.7%), high carbohydrate and protein intakes, as well as low mono- and polyunsaturated fatty acid intakes (including omega 3 and 6 fatty acids). No differences in nutritional status or intake were observed between patients with controlled versus uncontrolled seizures. CONCLUSIONS: patients with epilepsy have comorbidities risks, as evidenced by their tendency to overweight and obesity, and abdominal obesity. Although seizure control did not appear to be related to nutritional status and intake, the presence of such comorbidities underscores the need for nutritional monitoring and intervention in these patients, with a special focus on macronutrient redistribution and on dietary fatty acid levels. PMID- 26268117 TI - BLOOD PRESSURE IN HYPERTENSIVE WOMEN AFTER AEROBICS AND HYDROGYMNASTICS SESSIONS. AB - INTRODUCTION: regular exercise has been recommended as an important behavior in controlling blood pressure. In recent years it has been demonstrated that a single session of exercise can lower blood pressure levels compared to pre exercise period, becoming an effective non-pharmacological therapy for the treatment of hypertension. OBJECTIVE: the purpose of this study was to analyze the levels of blood pressure in post-exercise period of controlled hypertension women after an aerobics session and a hydrogymnastics session. METHODS: twelve elderly (65 +/- 3.6 years) who practice regular physical activity for at least two months had their levels of blood pressure measured during 60 minutes after the end of each session. Blood pressure was measured every five minutes after the end of each session until the twentieth minute of recovery. Following, blood pressure was measured every ten minutes. T-student test was used to compare mean and the level of significance adopted was 5%. RESULTS: the mean values of hypotension found during the recovery period after the hydrogymnastics session were not significantly different when compared to blood pressure levels of the pre-exercise period (p = 0.260). However, the result of the same comparison for the aerobics session was statistically significant (p < 0.001). The lowest values of systolic blood pressure reached in the recovery period for hydrogymnastics (120 mmHg) and aerobics (106 mmHg) were significantly different (p < 0.001). CONCLUSIONS: the aerobics session showed to be more effective in reducing post exercise blood pressure compared to the hydrogymnastics. After practice aerobics, the participants presented lower blood pressure levels and longer duration of the hypotensive effect. PMID- 26268118 TI - [THE COMPARISON BETWEEN FOOD HABITS AND PHYSICAL CONDITION AMONG PHYSICAL EDUCATION AND OTHER UNDERGRADUATE STUDENTS]. AB - INTRODUCTION: college students show a great susceptibility to acquire inadequate habits during their university studies, which they could maintain along their life. OBJECTIVE: compare the dietary habits and physical fitness among physical education students and other university careers at the same university and campus. METHODS: the sample included 343 students, mainly men (70%), 212 students from the career of Physical Education (PE) and 131 students of other careers (OC) of the Universidad Autonoma de Chile, Temuco campus. A validated survey about eating habits and physical fitness tests were applied to each student. RESULTS: in comparison with the students from other careers, the men of PE have a lower frequency of consumption of dairy, vegetables, alcohol (p < 0.05) and women of PE have higher frequency of consumption of homemade food, biscuits and sweet snacks (p < 0.05). Regarding the physical fitness, PE students obtained the best performance as was expected. CONCLUSION: no major differences were observed among the eating habits of students PE and OC from the same university, while physical fitness is consistent with the greater stimulus that the PE students receive in their academic training, which would serve as a excuse to consume more sugary drinks, junk food, cookies and sweet snacks. PMID- 26268119 TI - [USE, EFFECTS, AND KNOWLEDGE OF THE NUTRITIONAL SUPPLEMENTS FOR THE SPORT IN UNIVERSITY STUDENTS]. AB - BACKGROUND: consumption and marketing of supplements that help improve athletic performance has increased in semi-professional sport. Moreover, in the market are increasingly a wide variety of such products pressure and high performance requirements push many young athletes to have recourse to the use of supplements to improve your fitness. However, this type of treatment should be advised and guided by an expert since improper use of such supplements favors the appearance of adverse effects and can be harmful to the health of the individual. OBJECTIVE: to know the use of supplements to improve athletic performance by college athletes methods: was a systematic review in the Pubmed database, care, BIREME CUIDEN, BIREME (IBECS y Scielo) and CINHAL limited to articles published in the last ten years. RESULTS: 25 articles were analyzed. The main themes were found in the literature reviewed have been three: the "levels of supplements to increase athletic performance in college students", "effect of sports supplements" and "knowledge, behaviors and motivations for sports supplements". CONCLUSIONS: taking into account that the around 55% of University athletes using supplements but show a lack significant knowledge is necessary to provide a health education on such supplements. PMID- 26268120 TI - EVALUATION OF EFFICACY AND EFFECTIVENESS OF PRENATAL NUTRITIONAL CARE ON PERINATAL OUTCOME OF PREGNANT WOMEN; RIO DE JANEIRO, BRAZIL. AB - AIM: to evaluate the impact of a prenatal nutritional assistance proposal (PNA) for adult pregnant women. METHODS: a study of the impact of an applied nutritional intervention throughout the prenatal on perinatal outcomes - adequacy of total gestational weight gain, gestational anemia frequency and pregnancy complications in a public maternity hospital in Rio de Janeiro. The data represent three groups of adult pregnant women, during 10 years: GI (1999-2001, n = 225), GII (2005-2006, n = 208) and GIII (2007-2008, n = 394). RESULTS: in GII (reference group) it was included a detailed nutritional assessment, an individualized eating plan and an attendance of at least four scheduled appointments with a nutritionist. PNA coverage occurred in only 20.4% of GI, 100% of GII and 42.1% in GIII (p < 0.001). Women in GI had a higher proportion of inadequate total weight gain (OR 1.82, 95% CI: 1.20 -2.75), anemia (OR 2.18, 95% CI: 1.35 - 3.55) and pregnancy complications (OR 1.57, 95% CI: 1.04 - 2.36), as well as those who joined GIII, - OR 1.68 (95% CI: 1.16 - 2.44), OR 2.45 (95% CI: 1.56 - 3.84), OR 2.07 (95% CI: 1.42 - 3.00) - when compared to women in GII. CONCLUSIONS: the model tested in GII PNA demonstrated to be effective in the outcomes studied. PMID- 26268121 TI - [SOFT DRINKS CONSUMPTION AMONG PREGNANT WOMEN IN COLOMBIA: FACTORS ASSOCIATED]. AB - OBJECTIVE: to examine the factors associated with regular consumption of soft drinks in Colombian pregnant. MATERIAL AND METHODS: a cross-sectional study was conducted of data from the 2010 National Nutrition Survey of Colombia (ENSIN 2010), in 1.865 pregnant women aged between 13 and 49 years. Soft drink consumption and associated factors (pregnancy trimester, age, ethnicity, urbanicity, academic level, SISBEN score, and geographic region) were collected by structured questionnaire. Associations were established through a multivariable regression model. RESULTS: we found the 17% of pregnant women consume at least a daily soft drink. To be between 13 to 17 years old, belonging to an ethnic groups (afro-Colombian), being in the first pregnancy trimester and to belong to Sisben level II showed the highest daily consumption pattern (23.8%, 22.8%, 21.4% and 20.9%). Regression models show that being between 13 to 17 years old OR 1.92 (IC95% 1.04-3.55); to reside in the eastern area OR 1.85 (IC95% 1.05 3.27), or central OR 1.73 (IC95% 1.01- 2.96), and being in the first pregnancy trimester OR 1.59 (IC95% 1.01-2.52); were associated with soft drinks daily consumption. CONCLUSIONS: the women studied show a high prevalence of daily consumption of soft drinks. Comprehensive interventions involving both nutritional and educational components are required. PMID- 26268122 TI - ASSESSMENT OF THE FOOD PATTERNS OF IMMIGRANT ECUADORIAN POPULATION IN SOUTHERN SPAIN BASED ON A 24-H FOOD RECALL SURVEY. AB - INTRODUCTION: Ecuador is a country with limited nutritional information, with exception of some general studies supported by Food Agriculture Organization (FAO) Aims: to carry out a nutritional assessment of the diet of Ecuadorian immigrant population in Southern Spain to determine differences in food patterns and possible nutritional deficiencies. METHODS: the nutritional assessment was based on a 24-h food recall survey applied to the Ecuadorian population residing in Seville and Cordoba (Spain) in combination with the application of national and international food composition data bases. Nutrient intake levels and fulfillment of Dietary Reference Intakes (DRIs) were estimated and statistically tested for social, sex, age and geographical factors. RESULTS: macronutrient distributions and nutrient intake levels in relation with DRIs were adequate in most cases. Importantly, Ecuadorian food habits were still present in immigrant population, with rice being the main energy source. Intakes levels were significantly different for several nutrients depending on age group, sex, place of residence and professional occupation. Comparison with previous nutritional data from Ecuador revealed a better nutritional status of immigrant population in Spain, though deficiencies in fiber, vitamin E, I and Se were detected in the diet of both populations. Nevertheless, data for these deficiencies were insufficient to be conclusive given both limitations in the food composition data bases (e.g. Se) and the lack of more adequate information tools for its assessment (e.g. long-term studies for vitamin E). CONCLUSIONS: the results in the present study evidenced that Ecuadorian immigrants in Spain showed more adequate food patterns that those reported for Ecuador. These data can be helpful to get further insight into the nutritional value of Ecuadorian diet and develop suitable nutrition intervention. PMID- 26268123 TI - [OSTEOPOROSIS AND BODY MASS INDEX IN RENAL TRANSPLANT RECIPIENTS]. AB - INTRODUCTION: frequently after kidney transplantation there is an increase in weight with a resulting high percent of obesity in these recipients. This combined with a rapid loss of bone mass, a higher prevalence of osteoporosis and fractures is evident than in normal populations. OBJECTIVES: to explore the relationship between body mass index (BMI) and prevalence of osteoporosis in a population of renal transplant recipients. METHODS: prospective longitudinal study design. The study was conducted on 306 kidney transplant recipients. The relationship between weigh and body mass index with femoral and lumbar osteopenia and osteoporosis prevalence at the moment of transplant and at 12 months post was explored. RESULTS: there was a high prevalence of overweight (35.6%) and obese (14.1%) recipients after renal transplant and 1 year after (42.2% and 24.2% respectively). Significant differences were found(p = 0.049) between the weight at the time of transplant and the presence of osteopenia or osteoporosis at the lumbar level one year after, the highest weights were in recipients with osteoporosis. The mean BMI was higher (p = 0.028) in osteoporotic patients (26.59 kg/m2) than in patients with osteopenia (24.23 kg/m2). CONCLUSION: results seem to be consistent with recent studies in the general population showing excessive weight as a possible factor detrimental to the bone health. PMID- 26268124 TI - NUTRITIONAL STATUS AND PERIOPERATIVE FASTING TIME VERSUS COMPLICATIONS AND HOSPITAL STAY OF SURGICAL PATIENTS. AB - INTRODUCTION: many factors can have a negative influence over surgical results, such as a compromised nutritional status and the extension of the perioperative fasting time. OBJECTIVE: to evaluate the influence of the nutritional status and the perioperative fasting time over the occurrence of surgical complications and over hospital stay, in patients who have undergone surgery of the gastrointestinal tract and/or abdominal wall, and who were subjected to a nutritional care protocol. METHODS: cohort study, conducted with 84 patients, from June to November 2014. Data collection was performed by applying a structured questionnaire, search over the records and medical and/or nutritional prescription. Statistical analysis was performed using STATA/SE 12.0 and significance level of 5%. RESULTS: nutritional risk was present in 26.2%, and from these 45.4% carried out preoperative nutritional therapy, having an average of 6.6 +/- 2.79 days. The preoperative fasting was 4.5 (3.66; 5.50) hours and the postoperative fasting 5.1 (2.5; 20.5) hours. No associations were found between the parameters for assessing body composition and the presence of complications. A negative correlation was observed between the length of hospital stay and the BMI (p = 0.017),while a positive correlation was observed between weight loss and the length of hospital stay (p = 0.036). Patients with higher postoperative fasting time had a higher occurrence of complications (p = 0.021). CONCLUSION: the compromised nutritional status and the extension of perioperative fasting time are associated with the occurrence of surgical complications and increased length of hospital stay. PMID- 26268125 TI - [AGREEMENT BETWEEN INDIRECT CALORIMETRY AND PREDICTIVE EQUATIONS IN A SAMPLE OF SPANISH HEALTHY ADULTS]. AB - OBJECTIVE: the aim of this study was to analyze the agreement between the resting energy expenditure (REE) obtained by indirect calorimetry (IC) and that obtained by prediction equations in a sample of healthy adults from Spain. Methods: a descriptive cross-sectional study was conducted in 95 healthy, normal-weight adults. REE was determined by IC and 45 population-specific prediction equations which were based on weight, height, sex and/or body composition (BC). The Intraclass Correlation Coefficient (ICC) and Bland-Alman plots were used to analyze the agreement between the REE obtained by IC and that obtained by prediction equations. The level of signification was reached at p < 0,05. RESULTS: mean age was 42 years (range: 23.0-63.2). Mean REE determined by CI was 1589 (312) kcal/d [1822.3 (224.3) kcal/d in men and 1379.3 (216.1) kcal/d in women; p < 0.05]. The De-Lorenzo, Harris-Benedict, Schofield, and especially the Korth equations showed the greatest level of agreement with respect to IC. CONCLUSIONS: there is high variability in the estimates of REE depending on the prediction equation used. The De Lorenzo, Harris-Benedict, and the Schofield equations showed a good level of agreement in our sample; however, the Korth equation was the most appropriate. Equations based on weight and/or height were more accurate than those which included body composition variables. PMID- 26268126 TI - CARDIOVASCULAR RISK AND ASSOCIATED FACTORS IN ADOLESCENTS. AB - BACKGROUND: changes in lifestyle are related to early exposure of adolescents to comorbidities associated with cardiovascular disease. These conditions may have consequences in adulthood. OBJECTIVE: to determine the prevalence of cardiovascular risk and its associated factors in the three phases of adolescence. METHODS: a cross-sectional study involving adolescents 10-19 years old in the city of Vicosa distributed in three stages. We evaluated laboratory tests, body mass index classified into Z-score according to gender and age, and the percentage of body fat classified by gender. We used the chi-square test, chi square partition with Bonferroni correction and Poisson regression. The significance level was alpha < 0.05. The project was approved by the UFV Committee of Ethics and Research with Humans. RESULTS: overweight, excess body fat, lipid profile, sedentary behavior, and history of CVD in family were the most prevalent cardiovascular risk factors among adolescents. The adolescents had higher rates of overweight and excess fat. As for the stages, the first one showed a higher percentage of individuals with sedentary behavior, overweight, total cholesterol and LDL in comparison with other stages. Individuals with changes in nutritional status were more likely to develop hypertension, changes in total cholesterol, LDL, triglycerides, insulin, HOMA and low HDL when compared to healthy individuals. CONCLUSIONS: the cardiovascular risk factors have been observed in younger and younger individuals and are important factors to identify a population at risk. PMID- 26268127 TI - ASSOCIATION OF HELICOBACTER PYLORI INFECTION WITH NUTRITIONAL STATUS AND FOOD INTAKE. AB - INTRODUCTION: the H. pylori infection affects more than half of humanity, being a public health problem. Its prevalence is significantly higher in developing countries like Brazil. It has been suggested that H. pylori infection may influence the intake and caloric homeostasis. PURPOSE: to compare nutritional status and food intake of patients attended by National Health System, with and without H. pylori infection. METHODS: 140 patients were assessed. They performed upper gastrointestinal endoscopy to investigate the presence of H. pylori. Body weight and height of the patients were measured. Food intake was investigated through two 24-hour recalls, with data transformed in grams and analyzed in DietWin Professional 2.0 software. The findings were compared using the chi square test or Student's t-test, adopting p < 0.05 as significance level. RESULTS: there was predominance of patients with excess weight for both Hp - (60.3%) and Hp + (67.7%), with no difference between them. Food intake of assessed groups was similar. CONCLUSION: no differences were found in nutritional status and food intake between the two studied groups. PMID- 26268128 TI - STUDY ON THE DIFFERENCES OF MAJOR PHARMACEUTICAL INGREDIENTS IN DIFFERENT PARTS AND PROCESSED MEDICINAL MATERIAL OF EPIMEDIUM BREVICORNU MAXIM IN TAIHANG MOUNTAIN. AB - The aim of this study is to evaluate the medicinal values of different parts of Epimedium brevicornu Maxim. and the effect of processing on major pharmaceutical ingredients in it. The contents of icariin and epimedin C in different parts and processed medicinal material of E. brevicornu in Taihang Mountain were determined with ultrasonic extraction and RP-HPLC. The results indicated that the contents of icariin and epimedin C, respectively 3.4524% and 0.5485%, in the leaf are higher than that in other parts. The contents of icariin and epimedin C, respectively 0.1942 % and 0.1342%, in the stem (include petiole) are the lowest. The contents of these ingredients in the root (include rhizome) are close to that in the leaf. The icariin and epimedin C in all parts of E. brevicornu reduced after processing. The content of icariin in the processed leaf is about 59.5% of that in unprocessed leaves. The effect of prossing on the content of icariin in the stem is unobvious. The content of epimedin C in the processed leaf is about 33.7% of that in unprocessed leaf. The content of epimedin C in the processed stem (include petiole) is about 36.9% of that in unprocessed stem. It is worth to exploit the stem and petiole of E. brevicornu because there are certain contents of pharmaceutical ingredients in them. The firepower should be paid attention to and the temperature should not be very high to avoid the damage on pharmaceutical ingredients in E. brevicornu when process it. PMID- 26268129 TI - PREVALENCE OF AUTOIMMUNE THYROIDITIS AND THYROID DYSFUNCTION IN HEALTHY ADULT MEXICANS WITH A SLIGHTLY EXCESSIVE IODINE INTAKE. AB - OBJECTIVE: the purpose of this study was to evaluate the prevalence of autoimmune thyroiditis and thyroid dysfunction in healthy individuals with no previously known thyroid disease, in an urban area of Mexico City. SUBJECTS AND METHODS: the study was conducted on volunteers with no known thyroid disease. We recruited 427 subjects among the hospital's medical and administration personnel. All underwent thyroid ultrasound (US) and TSH, free T4 (FT4), total T3 (TT3), thyroid anti peroxidase (TPOAb) and anti-thyroglobulin (TgAb) antibodies were measured. Hypoechogenicity and thyroid volume were determined by US. Urinary iodine (UI) excretion was also measured. RESULTS: the frequency of autoimmune thyroiditis was 8.4% (36/427) and women were most commonly affected than men (11.6 vs. 4.3% respectively, P = 0.008); when including cases of atrophic thyroid, the frequency increased to 15.7% (67/427). Clinical hypothyroidism was detected in 1.2% (5/427) and it was sub-clinical in 5.6% of individuals. A goiter was present in 5.9% (25/427) of volunteers. Median UI was 267 MUg/L, (IQR 161.3 - 482.5). CONCLUSIONS: in spite of our study's limitations, the frequency of autoimmune thyroiditis is clearly elevated in the studied population. Further studies are necessary in order to define the prevalence of autoimmune thyroid disease as well as the current iodine nutritional status in our country. PMID- 26268130 TI - TRANSLATION AND VALIDATION OF THE FOOD NEOPHOBIA SCALE (FNS) TO THE BRAZILIAN PORTUGUESE. AB - INTRODUCTION: The Food Neophobia Scale (FNS), originally developed in English, has been widely used in different studies to assess the individual's willingness to try new foods. However, a process of translation and cultural adaptation is required to enable the use of FNS in other countries. OBJECTIVE: to translate and to validate the FNS into Brazilian Portuguese. METHODS: the FNS was translated into Brazilian Portuguese by three English teachers independently and back translated into English by other three professionals. After that, both the English and Brazilian Portuguese FNS versions were administered to a sample of 40 graduate students of the University of Campinas, Sao Paulo, Brazil, between September and October 2014. The reproducibility between the instruments was assessed by the intra-class correlation coefficient (ICC). The internal reliability of the scale was evaluated by Cronbach's Alpha coefficient. The FNS total score ranged from 10-70 and the respondents were classified as food neophilic (<= 16.4), neutral (16.5-38.5) and food neophobic (>= 38.6). RESULTS: the ICC between the items of the original FNS and the Brazilian FNS ranged between 0.266 and 0.815 (P < 0.05). The total score of the FNS was 0.903 (p < 0.001). Cronbach's alpha coefficient was 0.916. Most respondents were classified as neutral (72.5%), other 10% as neophilics, and only 17.5% as neophobics. CONCLUSION: the Brazilian version of the FNS proved to be an adequate and reliable tool to measure food neophobia. Yet, further research is required to investigate the presence of food neophobia in Brazilian population and to analyse its impact on food behavior. PMID- 26268131 TI - THE CONSUMPTION OF ACAI PULP CHANGES THE CONCENTRATIONS OF PLASMINOGEN ACTIVATOR INHIBITOR-1 AND EPIDERMAL GROWTH FACTOR (EGF) IN APPARENTLY HEALTHY WOMEN. AB - INTRODUCTION: obesity, characterized by adiposity excess, is associated with endothelial dysfunction and possible inflammatory state with release of cytokines that determine endothelial function and can trigger chronic diseases. The dietary pattern are associated with the synthesis these cytokines. Fruits as the acai, which is rich in flavonoids, have a direct and beneficial effect on the control of this inflammatory process through the exercised antioxidant capacity. OBJECTIVE: to evaluate the effect of acai pulp consumption on the inflammatory markers, anthropometric measurements, body composition, biochemical and dietary parameters in healthy women. METHODS: forty women, were divided in 25 eutrophic and 15 with overweight. They intaked 200 g of acai pulp during 4 weeks. Anthropometric measurements, body composition, inflammatory markers, biochemical data, dietary intake and dietary antioxidants capacity were evaluated before and after the intervention. RESULTS AND DISCUSSION: after the intervention, there was significant increase of EGF (p = 0.021) and PAI- 1(p = 0.011) in overweight women. Moreover, there was increase in body weight (p = 0.031), body mass index (p = 0.028), percentage of truncal fat (p = 0.003) and triceps skinfold thickness (p = 0.046) in eutrophic women. However, the skinfold thickness (p = 0.018) and total body fat (p = 0.016) decreased in overweight women. There was reduction of total protein (p = 0.049) due to the globulin reduction (p = 0.005), but the nutritional status was maintained in eutrophic group. CONCLUSION: the intake of 200g acai pulp, modulated the EGF and PAI-1 expression, possibly by modulation of acai on the parameters of body composition, dietary, clinical, biochemical and inflammatory, led to a redistribution and resizing of body fat of the trunk area, and presumably increased visceral fat. PMID- 26268132 TI - [NEURODEGENERATIVE DISEASES; NUTRITIONAL ASPECTS]. AB - INTRODUCTION: neurodegenerative diseases cause changes in the level of consciousness or swallowing mechanisms that often necessitate a specialized nutritional support. OBJECTIVE: review the risk of malnutrition and its treatment in patients with cerebral vascular disease, Parkinson's disease, dementia and amyotrophic lateral sclerosis. DEVELOPMENT: degenerative neurological diseases are one of the main indications for nutritional support in our country. In acute processes (cerebral vascular disease), proper nutritional management is related to better outcomes and reduced complications. In chronic neurodegenerative processes (amyotrophic lateral sclerosis and dementia), malnutrition is a major problem that worsens the prognosis of these patients, the proper management of dysphagia and its complications, as well as the use of different stages of support being necessary nutritional. A correct nutritional evaluation of these patients and a right nutrition intervention is essential in monitoring their disease. Finally, in advanced Parkinson's disease, nutritional support, as in previous neurodegenerative diseases, is of huge importance. Protein dietary load and its distribution in the diet of these patients are important, too. Finally, American Society for Parenteral and Enteral Nutrition ASPEN recommend, with a degree of evidence B, performing a screening of malnutrition in patients with neurological diseases. CONCLUSIONS: a correct nutritional evaluation and adequate nutritional support should be part of diagnostic and therapeutic process of these diseases. PMID- 26268133 TI - ORGANIC INFLAMMATORY RESPONSE TO REDUCED PREOPERATIVE FASTING TIME, WITH A CARBOHYDRATE AND PROTEIN ENRICHED SOLUTION; A RANDOMIZED TRIAL. AB - BACKGROUND: this study aims to assess the organic inflammatory response of the video laparoscopic cholecystectomy, with abbreviation of the preoperative fasting to 2h using a carbohydrate and protein enriched solution. METHODS: this is a randomized, prospective study with patients divided into the following 2 groups: group A, conventional fasting and group B, 2h abbreviated fasting with oral ingestion of a carbohydrate and protein solution. Serum glucose, insulin, interleukin 1, and TNF-alpha were mesasured before ingestion of the solution, during induction of anesthesia, and 4 h after the end of surgery. RESULTS: thirty eight patients completed the study without presenting pulmonary complications associated with bronchoaspiration. The postoperative HOMA-IR variance was greater in group A (p = 0.001). CONCLUSION: the abbreviation of preoperative fasting for 2 h, using carbohydrate and protein enriched solutions, is safe, reduces insulin resistance, and does not increase the risk of bronchoaspiration. PMID- 26268134 TI - [FIGURES PERFORMANCE OF GLYCEMIA IN TYPE 2 DIABETIC PATIENTS WITH INTAKE OF TWO BREAKFAST WITH THE SAME AMOUNT OF CARBOHYDRATES]. PMID- 26268135 TI - [IMPORTANCE OF THE METHODOLOGY REPORT IN ELECTRICAL BIOIMPEDANCE ON BODY COMPOSITION STUDIES]. PMID- 26268137 TI - Doppler Non-invasive Monitoring of ICP in an Animal Model of Acute Intracranial Hypertension. AB - BACKGROUND: In many neurological diseases, intracranial pressure (ICP) is elevated and needs to be actively managed. ICP is typically measured with an invasive transducer, which carries risks. Non-invasive techniques for monitoring ICP (nICP) have been developed. The aim of this study was to compare three different methods of transcranial Doppler (TCD) assessment of nICP in an animal model of acute intracranial hypertension. METHODS: In 28 rabbits, ICP was increased to 70-80 mmHg by infusion of Hartmann's solution into the lumbar subarachnoid space. Doppler flow velocity in the basilar artery was recorded. nICP was assessed through three different methods: Gosling's pulsatility index PI (gPI), Aaslid's method (AaICP), and a method based on diastolic blood flow velocity (FVdICP). RESULTS: We found a significant correlation between nICP and ICP when all infusion experiments were combined (FVdICP: r = 0.77, AaICP: r = 0.53, gPI: r = 0.54). The ability to distinguish between raised and 'normal' values of ICP was greatest for FVdICP (AUC 0.90 at ICP >40 mmHg). When infusion experiments were considered independently, FVdICP demonstrated again the strongest correlation between changes in ICP and changes in nICP (mean r = 0.85). CONCLUSIONS: TCD-based methods of nICP monitoring are better at detecting changes of ICP occurring in time, rather than absolute prediction of ICP as a number. Of the studied methods of nICP, the method based on FVd is best to discriminate between raised and 'normal' ICP and to monitor relative changes of ICP. PMID- 26268136 TI - Identification and characterization of a bovine sperm acrosomal matrix protein and its mechanism of interaction with acrosomal hydrolases. AB - Fertilization, the union of male and female gametes to create offspring, is an intricate biological process dependent upon several biochemical and physiological events. Our understanding of the functions of protein constituents of the outer acrosomal membrane-associated matrix complex (OMC) is limited. A highly purified OMC fraction isolated from bovine cauda sperm heads comprised 54, 50, 45, and 38 19 kDa polypeptides. The objective of this study is to identify and characterize the 45 kDa (OMC45) polypeptide, to define its role in binding acrosomal hydrolases, and to examine the fate of OMC45 polypeptide during the acrosome reaction. We isolated OMC45 polypeptide from the high-pH insoluble fraction of OMC. Proteomic analysis of OMC45 by MALDI-TOF-TOF yielded eight peptides that matched the NCBI database sequence of Tektin 3 (TEKT3). Triton X-100 permeabilized cauda sperm exhibited intense staining of the acrosomal segment with anti-OMC45 and anti-TEKT3. The OMC45 polypeptide was solubilized by radio immunoprecipitation assay buffer extraction. The solubilized fraction was subjected to immunoprecipitation analysis. The OMC45 polypeptide was recovered in the anti-OMC45 immunoprecipitation pellet. An identical blot stained with anti TEKT3 exhibited the presence of TEKT3 polypeptide in the anti-OMC45 pellet. Our immunofluorescence and biochemical studies confirm the proteomics identification of OMC45 polypeptide and that it exhibits a sequence similarity to TEKT3. OMC45 glycoprotein possesses both N-linked and O-linked oligosaccharides. Deglycosylated OMC45 revealed a significant reduction in both acrosin and N acetylglucosaminidase (NAGA) binding in comparison with acrosin and NAGA binding to a native OMC45 polypeptide, demonstrating the important role of oligosaccharides in hydrolase binding. OMC45 polypeptide is not released during the acrosome reaction but remains in the particulate cell subfraction, associated with the hybrid membrane complex. PMID- 26268138 TI - Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) Trial: Rationale and Design. AB - BACKGROUND: Patients with large territory infarction are at high risk of cerebral edema and neurological deterioration, including death. Preclinical studies have shown that a continuous infusion of glyburide blocks edema formation and improves outcome. We hypothesize that treatment with RP-1127 (Glyburide for Injection) reduces formation of brain edema in patients after large anterior circulation infarction. METHODS: GAMES-RP is a prospective, randomized, double-blind, multicenter trial designed to evaluate RP-1127 in patients at high risk for the development of malignant cerebral edema. The study population consisted of subjects with a clinical diagnosis of acute severe anterior circulation ischemic stroke with a baseline diffusion-weighted image lesion between 82 and 300 cm(3) who are 18-80 years of age. The target time from symptom onset to start of study infusion was <=10 h. Subjects were randomized to RP-1127 (glyburide for injection) or placebo and treated with a continuous infusion for 72 h. RESULTS: The primary efficacy outcome was a composite of the modified Rankin Scale and the incidence of decompressive craniectomy, assessed at 90 days. Safety outcomes were the frequency and severity of adverse events, with a focus on cardiac- and glucose-related serious adverse events. CONCLUSIONS: GAMES-RP was designed to provide critical information regarding glyburide for injection in patients with large hemispheric stroke and will inform the design of future studies. PMID- 26268139 TI - Rotated stack-of-spirals partial acquisition for rapid volumetric parallel MRI. AB - PURPOSE: We present a volumetric sampling method that rotates the spiral interleaves of a stack of spirals (SOSP) trajectory for reduced aliasing artifacts using parallel imaging with undersampling. METHODS: The aliasing pattern in an undersampled SOSP acquisition was modified by consecutively rotating spiral interleaves in each phase-encoding plane. This allows a sampling scheme with a high reduction factor when using a volumetric multireceiver array. Phantom and in vivo brain images at a resolution of 1 * 1 * 2 mm(3) were acquired at 3T using a 32-channel coil. Images reconstructed with a reduction factor of 16 were compared for aliasing artifacts and geometry factor (g-factor). RESULTS: Phantom and in vivo brain image results revealed that the rotated SOSP acquisition with a reduction factor of 16 produces images with reduced aliasing and lower g-factors than images acquired without rotation. CONCLUSION: The proposed rotated SOSP sampling method is a highly efficient way to maximize the encoding power of volumetric receiver arrays in parallel imaging and is applicable to rapid volumetric scanning, including susceptibility-weighted imaging and functional MRI. Magn Reson Med 76:127-135, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26268140 TI - Sebaceous carcinoma within rippled/carcinoid pattern sebaceoma. AB - Although the histogenesis of sebaceous carcinomas remains unclear, the occurrence of intraepidermal or intraepithelial sebaceous carcinoma in the epidermis or conjunctiva may suggest de novo histogenesis. This report describes a case of sebaceous carcinoma within preexisting rippled/carcinoid pattern sebaceoma. This lesion was composed of two (benign and malignant) components, and the benign component of the lesion showed the typical features of a rippled/carcinoid pattern sebaceoma. Although evidence of trauma as well as a vertical orientation was seen in this lesion, the malignant component of the lesion showed histopathological evidence of malignancy (sebaceous carcinoma), such as the aggregations with irregular and infiltrated borders, a sheet-like growth pattern, and the cytopathological findings of the neoplastic cells, showing a high-grade of malignancy (a high mitotic index and abnormal mitotic figures). The immunohistochemical staining for p53, Ki-67 and D2-40 also favored this diagnosis. This sebaceous carcinoma component was considered to be the incipient stage of carcinoma within preexisting sebaceoma, therefore, it was still considered to be a vertically oriented lesion. This case shows the possibility that abnormal (malignant) sebaceous germinative cells may originate within a sebaceoma, thereby suggesting that some sebaceous carcinomas may develop from preexisting sebaceomas. PMID- 26268141 TI - Voluntary breath-holding for breast cancer radiotherapy is consistent and stable. AB - OBJECTIVE: To evaluate breath-hold stability and constancy for a voluntary breath hold (VBH) technique in a retrospective analysis. METHODS: Movie loop sequences of electronic portal image data from multiple breath holds in a cohort of 19 patients were used to assess within and between breath-hold stability. In vivo dosimetry data based on electronic portal imaging (EPI) were analysed for 31 VBH patients plus a cohort of free-breathing (FB) patients to provide a reference. A phantom experiment simulated the impact on dose of FB, breath hold and unplanned release of breath hold. RESULTS: 165/174 (93%) movie loop data sets had no detectable displacement. For the remaining 12, median displacement = 1.5 mm and maximum displacement = 3 mm (one patient on one fraction). In vivo dosimetry data analysis showed a median dose difference measured to planned of -0.2% (VBH) and 0.1% (FB). Dose distribution evaluation (gamma) pass rates were 84% (VBH) and 91% (FB) including the lung region; 93% and 96% with a lung override. Unplanned release of phantom breath-hold position changed median dose by <=1% and degraded gamma pass rates to 79-62%. Failing regions were mostly in the periphery of the treated volume. CONCLUSION: The data confirmed that multiple VBHs using visual monitoring are stable; in vivo dose verification via EPI was within expected and acceptable levels. ADVANCES IN KNOWLEDGE: These data provide further reassurance that VBH is a safe technique for cardiac sparing breast radiotherapy and support its rapid, widespread implementation. PMID- 26268142 TI - Quantified ultrasound elastography in the assessment of cutaneous carcinoma. AB - OBJECTIVE: To evaluate the feasibility of high-frequency ultrasound and ultrasound elastography (USE) in discriminating benign from malignant skin lesions in a prospective cohort study and to introduce the use of a "strain ratio" for evaluation of skin lesions. METHODS: A commercial ultrasound system with a 14-MHz transducer was used to visualize skin lesions requiring biopsy on clinical evaluation. Anatomic ultrasound and USE imaging of the skin lesions was performed using 2- to 4-mm gel stand-off pads. A region of interest was manually selected over the area of each lesion with the lowest strain. The concept of a strain ratio of the compressibility of the normal skin at the corresponding layer to that of the least compressible region of a lesion in question was created and applied. This ratio was subsequently correlated with blind histopathological evaluation for malignancy. RESULTS: 55 patients were included in the study with a total of 67 lesions evaluated. 29 lesions were malignant and 38 benign. All malignant lesions had strain ratios >=3.9. All benign lesions had strain ratios <=3.0. A diagnostic value between 3.0 and 3.9 would result in 100% sensitivity and specificity in the characterization of these lesions as malignant. CONCLUSION: This pilot study demonstrated that USE plus strain ratio appears to be a promising modality in providing diagnostic determination between cancerous and benign primary solitary skin lesions prior to biopsy. ADVANCES IN KNOWLEDGE: This is the first reported study applying an original mathematical elastographic ratio, or strain ratio, to evaluate primary solitary skin lesions. PMID- 26268143 TI - Pictorial review. Diagnosis of recurrent prostate cancer and its mimics at multiparametric prostate MRI. AB - Biochemical recurrence after treatment for prostate cancer (PCa) is a significant issue. Early diagnosis of local recurrence is important for making prompt treatment decisions and is strongly associated with patient prognosis. Without salvage therapy, the average time from development of local recurrence to distant metastasis is approximately 3 years. Biochemical recurrence does not differentiate local recurrence from systemic disease; there is no reliable way to clinically diagnose local recurrence. Recent advances in multiparametric MRI (mp MRI) techniques have markedly improved detection of local recurrence following therapy. However, a wide variety of entities can mimic recurrent PCa at mp-MRI. Therefore, the purpose of this pictorial review is to discuss the MRI findings of locally recurrent PCa and its mimics, emphasizing the key MRI features that help to differentiate local recurrence from its mimics. PMID- 26268144 TI - Multiparametric MRI of the prostate with three functional techniques in patients with PSA elevation before initial TRUS-guided biopsy. AB - OBJECTIVE: Multiparametric MRI (mp-MRI) of the prostate is increasingly being used for local staging and detection of recurrence of prostate cancer (PCA). In patients with elevated prostate-specific antigen (PSA), mp-MRI could provide information on the position of the cancer, allowing adjustments to be made to the needle depth and direction before repeat transrectal ultrasound (TRUS)-guided biopsy to ensure accurate sampling of lesions. The purpose of the prospective study was to evaluate mp-MRI of the prostate in patients with PSA elevation before initial TRUS-guided biopsy. METHODS: mp-MRI was performed in 94 patients using a 1.5-T scanner (MAGNETOM Aera((r)); Siemens Healthcare, Erlangen, Germany) and 16-channel phased-array body coil (Siemens Healthcare). T2 weighted images (T2WI), diffusion-weighted imaging (DWI), dynamic contrast-enhanced (DCE) MRI and MR spectroscopy were obtained. TRUS-guided random biopsies and additional targeted biopsies of suspicious MRI areas were performed. RESULTS: Additional targeted biopsies were obtained in 17 of 43 (40%) patients with PCA. 11 of 17 targeted biopsies contained PCA. 5 of 11 PCAs were diagnosed only by additional targeted biopsies. Sensitivity of mp-MRI in patients was 97.7% and specificity was 11.8%. mp-MRI was false negative in one patient. Sensitivity of mp-MRI in 207 lesions was 80.9% and specificity was 44.7%. In a logistic regression model, the apparent diffusion coefficient value was the only significant parameter to differentiate malignant and benign lesions. CONCLUSION: mp-MRI should be performed in patients with PSA elevation before initial TRUS-guided biopsy to allow additional targeted biopsies from suspicious areas of MRI. We recommend mp MRI with T2WI, DWI, DCE MRI and MR spectroscopy. DWI as the most reliable technique should be used in every mp-MRI. ADVANCES IN KNOWLEDGE: DWI is the most reliable technique in mp-MRI of the prostate. PMID- 26268145 TI - Oral operant ethanol self-administration in the absence of explicit cues, food restriction, water restriction and ethanol fading in C57BL/6J mice. AB - RATIONALE: Mouse models of ethanol (EtOH) self-administration are useful to identify genetic and biological underpinnings of alcohol use disorder. OBJECTIVES: These experiments developed a novel method of oral operant EtOH self administration in mice without explicitly paired cues, food/water restriction, or EtOH fading. METHODS: Following magazine and lever training for 0.2 % saccharin (SAC), mice underwent nine weekly overnight sessions with lever pressing maintained by dipper presentation of 0, 3, 10, or 15 % EtOH in SAC or water vehicle. Ad libitum water was available from a bottle. RESULTS: Water vehicle mice ingested most fluid from the water bottle in contrast to SAC vehicle mice, which despite lever pressing demands, drank most of their fluid from the liquid dipper. Although EtOH in SAC vehicle mice showed concentration-dependent increases of g/kg EtOH intake, lever pressing decreased with increasing EtOH concentration and did not exceed that of SAC vehicle alone at any EtOH concentration. Mice reinforced with EtOH in water ingested less EtOH than mice reinforced with EtOH in SAC. EtOH in water mice, however, showed concentration dependent increases in g/kg EtOH intake and lever presses. Fifteen percent EtOH in water mice showed significantly greater levels of lever pressing than water vehicle mice and a significant escalation of responding across weeks of exposure. Naltrexone pretreatment reduced EtOH self-administration and intake in these mice without altering responding in the vehicle control condition during the first hour of the session. CONCLUSIONS: SAC facilitated EtOH intake but prevented observation of EtOH reinforcement. Water vehicle unmasked EtOH's reinforcing effects. PMID- 26268147 TI - Hybrid transatrial stent insertion for left atrial decompression in hypoplastic left heart syndrome with intact atrial septum. AB - OBJECTIVES: To describe a novel strategy for the management of infants with hypoplastic left heart syndrome (HLHS) and intact atrial septum. Antenatally diagnosed infants are delivered in cardiac theatre and immediate left atrial decompression (LAD) using hybrid transatrial stent insertion (HTSI) via sternotomy is carried out. BACKGROUND: HLHS with intact atrial septum is a condition incompatible with life following placental separation. Despite a number of reported strategies the survival of these infants remains much worse than those born with an adequate atrial communication. Immediate postnatal LAD is mandatory to allow consideration of active treatment. METHODS: Single institution retrospective review of intention to carry out HTSI for LAD in infants with an antenatal diagnosis of HLHS intact atrial septum. RESULTS: Two patients were delivered by planned caesarean section and transferred immediately to the prepared team in the adjacent cardiothoracic theatre. Birth weights were 3.2 Kg and 2.96 Kg. Clinical condition was poor with mean arterial PaO2 2.8kPa intubated with 100% inspired oxygen. HTSI was performed using premounted 7 * 17 mm stents (Visi-ProTM, eV3 Endovascular, Plymouth, MN). Mean arterial PaO2 improved to 6.2 kPa. Mean time from surgical incision to LAD was 26 min. Bilateral pulmonary artery bands (BPAB) were then placed. No procedural complications occurred and both patients underwent subsequent surgical stage 1 Norwood at 6 and 10 days. CONCLUSIONS: In this high-risk anatomical substrate, careful planning from accurate fetal diagnosis underpins the success of initial management. This early experience suggests that HTSI offers rapid and successful postnatal LAD with no procedural morbidity facilitating successful subsequent palliation. (c) 2015 Wiley Periodicals, Inc. PMID- 26268146 TI - Effects of psychotropic drugs on inflammation: consequence or mediator of therapeutic effects in psychiatric treatment? AB - RATIONALE: Current psychotropic medications have been shown to modulate immune activation. However, the effects of individual psychotropic agents on the immune system and how these might contribute to their efficacy remain largely unclear. OBJECTIVE: This paper aims to review previous literature on the effects of antidepressants and antipsychotics on the immune system, with a systematic review of in vitro findings, and discuss the relevance of these effects for the response to treatment and future drug development. RESULTS: Inflammatory markers have been associated with fluctuations in clinical status and with treatment response both in depression and psychosis. The in vitro literature on antidepressants shows that some antidepressants, such as clomipramine and fluoxetine, more consistently decrease pro-inflammatory cytokines (interleukin (IL)-6, interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha), whilst others (mirtazapine and venlafaxine) tend to increase their levels. However, any overall conclusion is challenged by several inconsistent findings, which appear partly dependent on different methodological approaches used. The in vitro studies on antipsychotics are even less clear-cut showing pro- and anti-inflammatory activity for the same antipsychotic agent (haloperidol, clozapine, risperidone) across different studies. We also noted inconsistencies between in vivo and in vitro literature, which could partly be attributed to the interaction in vivo with various biological systems or lifestyle factors that can modulate the immune system. CONCLUSIONS: Inflammatory markers seem to hold potential for developing more individualised treatment strategies in the future. In this context, further research disentangling the differential immunomodulatory effects of different drugs could be used for tailoring treatment to specific individuals, according to their immune endophenotypes. PMID- 26268149 TI - Unilateral leg swelling: frequent symptom, rare diagnosis. A case of liposarcoma. PMID- 26268148 TI - Microfluidic-based fabrication, characterization and magnetic functionalization of microparticles with novel internal anisotropic structure. AB - Easy fabrication and independent control of the internal and external morphologies of core-shell microparticles still remain challenging. Core-shell microparticle comprised of a previously unknown internal anisotropic structure and a spherical shell was fabricated by microfluidic-based emulsificaiton and photopolymerization. The interfacial and spatial 3D morphology of the anisotropic structure were observed by SEM and micro-CT respectively. Meanwhile, a series of layer-by-layer scans of the anisotropic structure were obtained via the micro-CT, which enhanced the detail characterization and analysis of micro materials. The formation mechanism of the internal anisotropic structure may be attributed to solution-directed diffusion caused by the semipermeable membrane structure and chemical potential difference between inside and outside of the semipermeable membrane-like polymerized shell. The morphology evolution of the anisotropic structure was influenced and controlled by adjusting reaction parameters including polymerization degree, polymerization speed, and solute concentration difference. The potential applications of these microparticles in microrheological characterization and image enhancement were also proposed by embedding magnetic nanoparticles in the inner core. PMID- 26268150 TI - Optimal threshold of postintervention minimum stent area to predict in-stent restenosis in small coronary arteries: An optical coherence tomography analysis. AB - OBJECTIVES: The aim of this study was to determine the best threshold of postintervention minimum stent area (MSA) assessed by optical coherence tomography (OCT) to predict long-term in-stent restenosis (ISR) for 2.5 mm diameter everolimus-eluting stents (EES). BACKGROUND: Percutaneous coronary intervention (PCI) for small coronary arteries remains challenging. Stent underexpansion is a strong predictor of late ISR. METHODS: We performed a retrospective analysis of 69 lesions in 69 patients undergoing PCI with 2.5 mm diameter stents using OCT for the assessment of postintervention MSA and subsequent 9-month angiographic follow-up. RESULTS: The rates of angiographic ISR and target lesion revascularization were 7.2% and 1.4%. The postintervention OCT MSA of EES < 3.5 mm(2) for predicting ISR yielded a sensitivity of 80%, specificity of 71%, positive predictive value of 18%, and negative predictive value of 98%. There was a marginally significant trend between increasing MSA quartiles and decreasing ISR rate (P for trend = 0.07). CONCLUSIONS: Postintervention OCT-MSA of 3.5 mm(2) best predicted 9-month ISR following PCI with 2.5-mm-diameter EES. Further large, prospective, observational studies are warranted that validate this result. (c) 2015 Wiley Periodicals, Inc. PMID- 26268152 TI - Improving guideline sensitivity and specificity for the identification of proactive gastrostomy placement in patients with head and neck cancer. AB - BACKGROUND: Swallowing and nutrition guidelines for patients with head and neck cancer are available for identification of proactive gastrostomy placement in patients with high nutritional risk. The purpose of this study was to investigate improvements to the validity of these guidelines. METHODS: A multivariate analysis was fitted to the original dataset (n = 501) to examine the variables that may predict gastrostomy placement (eg, tumor site, treatment, sex, and age). Using these factors, the high risk category was modified and retrospectively validated in the same cohort to provide new measures of sensitivity and specificity. RESULTS: The following were positive predictors of gastrostomy placement: T3 (p = .01), T4 (p < .001), and chemoradiotherapy (p < .001). Laryngeal (p = .02) and skin cancer (p < .001) were negative predictors. Modification of the high risk definition improved sensitivity to 58% and maintained specificity at 92%. CONCLUSION: Minor modifications to the high risk definition in the guidelines have improved the guideline sensitivity for future use. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1163-E1171, 2016. PMID- 26268153 TI - Spatial correlations and optical properties in three-dimensional deterministic aperiodic structures. AB - Photonic systems have strongly varying optical properties depending on the spatial correlations present in a given realization. In photonic crystals the correlations are spatially periodic forming Bravais lattices whereas the building blocks of an amorphous medium are randomly distributed without any long-range order. In this manuscript we study the optical properties of so-called deterministic aperiodic structures which fill the gap between the aforementioned two limiting cases. Within this group we vary the spectrum of the spatial correlations from being pure-point over singularly-continuous to absolutely continuous. The desired correlations are created in direct-laser written three dimensional polymer structures using one construction principle which allows us to attribute the optical behaviour solely to the encoded spectrum. Infrared reflection measurements reveal the characteristic response of each spectral type verifying the successful fabrication of large deterministic aperiodic structures. To prove the presence of the correlations in all directions we perform transmission experiments parallel to the substrate by means of micro-optical mirrors placed next to the structures. Transport measurements reveal a strong dependence of the effective beam width at the output facet on the encoded lattice type. Finally, we reproduce the lattice type dependent transport behavior in numerical calculations ruling out extrinsic experimental reasons for these findings. PMID- 26268154 TI - A two-dimensional algebraic quantum liquid produced by an atomic simulator of the quantum Lifshitz model. AB - Bosons have a natural instinct to condense at zero temperature. It is a long standing challenge to create a high-dimensional quantum liquid that does not exhibit long-range order at the ground state, as either extreme experimental parameters or sophisticated designs of microscopic Hamiltonians are required for suppressing the condensation. Here we show that synthetic gauge fields for ultracold atoms, using either the Raman scheme or shaken lattices, provide physicists a simple and practical scheme to produce a two-dimensional algebraic quantum liquid at the ground state. This quantum liquid arises at a critical Lifshitz point, where a two-dimensional quartic dispersion emerges in the momentum space, and many fundamental properties of two-dimensional bosons are changed in its proximity. Such an ideal simulator of the quantum Lifshitz model allows experimentalists to directly visualize and explore the deconfinement transition of topological excitations, an intriguing phenomenon that is difficult to access in other systems. PMID- 26268151 TI - The maternal brain and its plasticity in humans. AB - This article is part of a Special Issue "Parental Care". Early mother-infant relationships play important roles in infants' optimal development. New mothers undergo neurobiological changes that support developing mother-infant relationships regardless of great individual differences in those relationships. In this article, we review the neural plasticity in human mothers' brains based on functional magnetic resonance imaging (fMRI) studies. First, we review the neural circuits that are involved in establishing and maintaining mother-infant relationships. Second, we discuss early postpartum factors (e.g., birth and feeding methods, hormones, and parental sensitivity) that are associated with individual differences in maternal brain neuroplasticity. Third, we discuss abnormal changes in the maternal brain related to psychopathology (i.e., postpartum depression, posttraumatic stress disorder, substance abuse) and potential brain remodeling associated with interventions. Last, we highlight potentially important future research directions to better understand normative changes in the maternal brain and risks for abnormal changes that may disrupt early mother-infant relationships. PMID- 26268155 TI - A start codon mutation of the FRMD7 gene in two Korean families with idiopathic infantile nystagmus. AB - Idiopathic infantile nystagmus (IIN) is the involuntary oscillation of the eyes with onset in the first few months of life. The most common form of inheritance is X-linked, and mutations in FRMD7 gene are a major cause. To identify the FRMD7 gene mutations associated with X-linked IIN, we performed PCR-based DNA direct sequencing in 4 affected subjects from 2 Korean families. We also assessed structural abnormalities of retina and optic nerve head using optical coherence tomography (OCT). Genetic analysis revealed a A>G transversion at nucleotide c.1, the first base of the start codon. This mutation leads to the loss of the primary start codon ATG for methionine, which is replaced by a triplet GTG for valine. The alternative in-frame start codon is not present around a mutation. OCT revealed the morphological changes within the optic nerve head, including shallow cup depth and small cup-to-disc ratio. In summary, we identified a novel start codon mutation within the FRMD7 gene of 2 Korean families. Our data expands the mutation spectrum of FRMD7 causing IIN. We also demonstrated abnormal developments of afferent system in patients with FRMD7 mutations using OCT, which may help to understand the etiological factor in development of nystagmus. PMID- 26268156 TI - Efficient Dynamic Nuclear Polarization at 800 MHz/527 GHz with Trityl-Nitroxide Biradicals. AB - Cross-effect (CE) dynamic nuclear polarization (DNP) is a rapidly developing technique that enhances the signal intensities in magic-angle spinning (MAS) NMR spectra. We report CE DNP experiments at 211, 600, and 800 MHz using a new series of biradical polarizing agents referred to as TEMTriPols, in which a nitroxide (TEMPO) and a trityl radical are chemically tethered. The TEMTriPol molecule with the optimal performance yields a record (1) H NMR signal enhancement of 65 at 800 MHz at a concentration of 10 mM in a glycerol/water solvent matrix. The CE DNP enhancement for the TEMTriPol biradicals does not decrease as the magnetic field is increased in the manner usually observed for bis-nitroxides. Instead, the relatively strong exchange interaction between the trityl and nitroxide moieties determines the magnetic field at which the optimum enhancement is observed. PMID- 26268157 TI - Aged care residents in the emergency department: the experiences of relatives. AB - AIMS AND OBJECTIVES: The aim of this study was to investigate the experiences of relatives who had a family member in an aged care facility subsequently transferred to an emergency department. BACKGROUND: The provision of timely and relevant patient information is vital for assessment and management of older patients presenting to the emergency department from aged care facilities. Older people are commonly accompanied by relatives who are an important resource for emergency department staff, providing medical information and assisting with treatment decisions. Investigating the experiences of relatives may provide key information to enable improvements in the delivery of emergency department care. DESIGN: This study used a descriptive qualitative design. METHODS: Semi structured interviews were undertaken with 24 relatives of residents who were transferred from an aged care facility to an emergency department in Victoria, Australia in the previous three years. Inductive content analysis was used to analyse the transcripts. RESULTS: Relatives reflected on four main themes following their emergency department visit: The need for clear communication; The role of relatives in emergency department care; How older people are perceived in the health care system and an Ability to provide specialised care. CONCLUSIONS: Many people link their emergency department experience to the quality of communication with emergency department staff, and participants in this study felt satisfied with their visit when they were included in discussions about treatment, and their role was recognised by staff members. In contrast, participants were dissatisfied with the care provided to their family member when staff members failed to communicate with them, or recognise their role in the care of the family member. RELEVANCE TO CLINICAL PRACTICE: The findings of this study emphasise the importance of effective communication between emergency department staff and family members, in relation to treatment and end-of-life care. PMID- 26268159 TI - Science in the community. PMID- 26268158 TI - Characterization of the ultrashort-TE (UTE) MR collagen signal. AB - Although current cardiovascular MR (CMR) techniques for the detection of myocardial fibrosis have shown promise, they nevertheless depend on gadolinium based contrast agents and are not specific to collagen. In particular, the diagnosis of diffuse myocardial fibrosis, a precursor of heart failure, would benefit from a non-invasive imaging technique that can detect collagen directly. Such a method could potentially replace the need for endomyocardial biopsy, the gold standard for the diagnosis of the disease. The objective of this study was to measure the MR properties of collagen using ultrashort TE (UTE), a technique that can detect short T2* species. Experiments were performed in collagen solutions. Via a model of bi-exponential T2* with oscillation, a linear relationship (slope = 0.40 +/- 0.01, R(2) = 0.99696) was determined between the UTE collagen signal fraction associated with these properties and the measured collagen concentration in solution. The UTE signal of protons in the collagen molecule was characterized as having a mean T2* of 0.75 +/- 0.05 ms and a mean chemical shift of -3.56 +/- 0.01 ppm relative to water at 7 T. The results indicated that collagen can be detected and quantified using UTE. A knowledge of the collagen signal properties could potentially be beneficial for the endogenous detection of myocardial fibrosis. PMID- 26268160 TI - The future of science will soon be upon us. PMID- 26268171 TI - Japan's nuclear revival won't lower carbon emissions enough. PMID- 26268172 TI - Millennium Villages Project launches retrospective analysis. PMID- 26268173 TI - GM-crop opponents expand probe into ties between scientists and industry. PMID- 26268174 TI - Proposed Ebola biobank would strengthen African science. PMID- 26268175 TI - Age of the neutrino: Plans to decipher mysterious particle take shape. PMID- 26268176 TI - Can randomized trials eliminate global poverty? PMID- 26268177 TI - Sustainability: Don't waste seafood waste. PMID- 26268181 TI - STEM teaching: use more innovations. PMID- 26268182 TI - Resources: Partner crop plants with solar facilities. PMID- 26268183 TI - Policy: The future of public trust in science. PMID- 26268184 TI - Sustainability: Solar ovens beaten by rain and tortillas. PMID- 26268185 TI - STEM teaching: avoid Swiss-cheese effect. PMID- 26268186 TI - Organic chemistry: A cure for catalyst poisoning. PMID- 26268187 TI - Particle physics: Matter and antimatter scrutinized. PMID- 26268188 TI - Longevity: Mapping the path to a longer life. PMID- 26268189 TI - High-precision comparison of the antiproton-to-proton charge-to-mass ratio. AB - Invariance under the charge, parity, time-reversal (CPT) transformation is one of the fundamental symmetries of the standard model of particle physics. This CPT invariance implies that the fundamental properties of antiparticles and their matter-conjugates are identical, apart from signs. There is a deep link between CPT invariance and Lorentz symmetry--that is, the laws of nature seem to be invariant under the symmetry transformation of spacetime--although it is model dependent. A number of high-precision CPT and Lorentz invariance tests--using a co-magnetometer, a torsion pendulum and a maser, among others--have been performed, but only a few direct high-precision CPT tests that compare the fundamental properties of matter and antimatter are available. Here we report high-precision cyclotron frequency comparisons of a single antiproton and a negatively charged hydrogen ion (H(-)) carried out in a Penning trap system. From 13,000 frequency measurements we compare the charge-to-mass ratio for the antiproton (q/m)p- to that for the proton (q/m)p and obtain (q/m)p-/(q/m)p - 1 =1(69) * 10(-12). The measurements were performed at cyclotron frequencies of 29.6 megahertz, so our result shows that the CPT theorem holds at the atto electronvolt scale. Our precision of 69 parts per trillion exceeds the energy resolution of previous antiproton-to-proton mass comparisons as well as the respective figure of merit of the standard model extension by a factor of four. In addition, we give a limit on sidereal variations in the measured ratio of <720 parts per trillion. By following the arguments of ref. 11, our result can be interpreted as a stringent test of the weak equivalence principle of general relativity using baryonic antimatter, and it sets a new limit on the gravitational anomaly parameter of |alpha - 1| < 8.7 * 10(-7). PMID- 26268190 TI - Rejuvenation of metallic glasses by non-affine thermal strain. AB - When a spatially uniform temperature change is imposed on a solid with more than one phase, or on a polycrystal of a single, non-cubic phase (showing anisotropic expansion-contraction), the resulting thermal strain is inhomogeneous (non affine). Thermal cycling induces internal stresses, leading to structural and property changes that are usually deleterious. Glasses are the solids that form on cooling a liquid if crystallization is avoided--they might be considered the ultimate, uniform solids, without the microstructural features and defects associated with polycrystals. Here we explore the effects of cryogenic thermal cycling on glasses, specifically metallic glasses. We show that, contrary to the null effect expected from uniformity, thermal cycling induces rejuvenation, reaching less relaxed states of higher energy. We interpret these findings in the context that the dynamics in liquids become heterogeneous on cooling towards the glass transition, and that there may be consequent heterogeneities in the resulting glasses. For example, the vibrational dynamics of glassy silica at long wavelengths are those of an elastic continuum, but at wavelengths less than approximately three nanometres the vibrational dynamics are similar to those of a polycrystal with anisotropic grains. Thermal cycling of metallic glasses is easily applied, and gives improvements in compressive plasticity. The fact that such effects can be achieved is attributed to intrinsic non-uniformity of the glass structure, giving a non-uniform coefficient of thermal expansion. While metallic glasses may be particularly suitable for thermal cycling, the non-affine nature of strains in glasses in general deserves further study, whether they are induced by applied stresses or by temperature change. PMID- 26268191 TI - Dosage delivery of sensitive reagents enables glove-box-free synthesis. AB - Contemporary organic chemists employ a broad range of catalytic and stoichiometric methods to construct molecules for applications in the material sciences, and as pharmaceuticals, agrochemicals, and sensors. The utility of a synthetic method may be greatly reduced if it relies on a glove box to enable the use of air- and moisture-sensitive reagents or catalysts. Furthermore, many synthetic chemistry laboratories have numerous containers of partially used reagents that have been spoiled by exposure to the ambient atmosphere. This is exceptionally wasteful from both an environmental and a cost perspective. Here we report an encapsulation method for stabilizing and storing air- and moisture sensitive compounds. We demonstrate this approach in three contexts, by describing single-use capsules that contain all of the reagents (catalysts, ligands, and bases) necessary for the glove-box-free palladium-catalysed carbon fluorine, carbon-nitrogen, and carbon-carbon bond-forming reactions. This strategy should reduce the number of error-prone, tedious and time-consuming weighing procedures required for such syntheses and should be applicable to a wide range of reagents, catalysts, and substrate combinations. PMID- 26268192 TI - The role of ridges in the formation and longevity of flat slabs. AB - Flat-slab subduction occurs when the descending plate becomes horizontal at some depth before resuming its descent into the mantle. It is often proposed as a mechanism for the uplifting of deep crustal rocks ('thick-skinned' deformation) far from plate boundaries, and for causing unusual patterns of volcanism, as far back as the Proterozoic eon. For example, the formation of the expansive Rocky Mountains and the subsequent voluminous volcanism across much of the western USA has been attributed to a broad region of flat-slab subduction beneath North America that occurred during the Laramide orogeny (80-55 million years ago). Here we study the largest modern flat slab, located in Peru, to better understand the processes controlling the formation and extent of flat slabs. We present new data that indicate that the subducting Nazca Ridge is necessary for the development and continued support of the horizontal plate at a depth of about 90 kilometres. By combining constraints from Rayleigh wave phase velocities with improved earthquake locations, we find that the flat slab is shallowest along the ridge, while to the northwest of the ridge, the slab is sagging, tearing, and re initiating normal subduction. On the basis of our observations, we propose a conceptual model for the temporal evolution of the Peruvian flat slab in which the flat slab forms because of the combined effects of trench retreat along the Peruvian plate boundary, suction, and ridge subduction. We find that while the ridge is necessary but not sufficient for the formation of the flat slab, its removal is sufficient for the flat slab to fail. This provides new constraints on our understanding of the processes controlling the beginning and end of the Laramide orogeny and other putative episodes of flat-slab subduction. PMID- 26268195 TI - X-ray absorption resonances near L2,3-edges from real-time propagation of the Dirac-Kohn-Sham density matrix. AB - The solution of the Liouville-von Neumann equation in the relativistic Dirac-Kohn Sham density matrix formalism is presented and used to calculate X-ray absorption cross sections. Both dynamical relaxation effects and spin-orbit corrections are included, as demonstrated by calculations of the X-ray absorption of SF6 near the sulfur L2,3-edges. We also propose an analysis facilitating the interpretation of spectral transitions from real-time simulations, and a selective perturbation that eliminates nonphysical excitations that are artifacts of the finite basis representation. PMID- 26268196 TI - What's in this issue? PMID- 26268193 TI - The octopus genome and the evolution of cephalopod neural and morphological novelties. AB - Coleoid cephalopods (octopus, squid and cuttlefish) are active, resourceful predators with a rich behavioural repertoire. They have the largest nervous systems among the invertebrates and present other striking morphological innovations including camera-like eyes, prehensile arms, a highly derived early embryogenesis and a remarkably sophisticated adaptive colouration system. To investigate the molecular bases of cephalopod brain and body innovations, we sequenced the genome and multiple transcriptomes of the California two-spot octopus, Octopus bimaculoides. We found no evidence for hypothesized whole-genome duplications in the octopus lineage. The core developmental and neuronal gene repertoire of the octopus is broadly similar to that found across invertebrate bilaterians, except for massive expansions in two gene families previously thought to be uniquely enlarged in vertebrates: the protocadherins, which regulate neuronal development, and the C2H2 superfamily of zinc-finger transcription factors. Extensive messenger RNA editing generates transcript and protein diversity in genes involved in neural excitability, as previously described, as well as in genes participating in a broad range of other cellular functions. We identified hundreds of cephalopod-specific genes, many of which showed elevated expression levels in such specialized structures as the skin, the suckers and the nervous system. Finally, we found evidence for large-scale genomic rearrangements that are closely associated with transposable element expansions. Our analysis suggests that substantial expansion of a handful of gene families, along with extensive remodelling of genome linkage and repetitive content, played a critical role in the evolution of cephalopod morphological innovations, including their large and complex nervous systems. PMID- 26268197 TI - A roadmap for paediatric and neonatal critical care nursing science in Europe: engage, action and impact. PMID- 26268198 TI - To cure sometimes, to relieve often and to comfort always: nurses' role in end-of life decision-making. PMID- 26268201 TI - A letter from Catherine Jones (Winner of Southern Region's June study day prize). PMID- 26268209 TI - Erratum to: Survival of Hendra Virus in the Environment: Modelling the Effect of Temperature. PMID- 26268210 TI - Assessing the Evidence Supporting Fruit Bats as the Primary Reservoirs for Ebola Viruses. PMID- 26268211 TI - The mineralocorticoid receptor plays a transient role in mouse skin development. PMID- 26268215 TI - Conservation of tRNA and rRNA 5-methylcytosine in the kingdom Plantae. AB - BACKGROUND: Post-transcriptional methylation of RNA cytosine residues to 5 methylcytosine (m(5)C) is an important modification that regulates RNA metabolism and occurs in both eukaryotes and prokaryotes. Yet, to date, no transcriptome wide identification of m(5)C sites has been undertaken in plants. Plants provide a unique comparative system for investigating the origin and evolution of m(5)C as they contain three different genomes, the nucleus, mitochondria and chloroplast. Here we use bisulfite conversion of RNA combined with high throughput IIlumina sequencing (RBS-seq) to identify single-nucleotide resolution of m(5)C sites in non-coding ribosomal RNAs and transfer RNAs of all three sub cellular transcriptomes across six diverse species that included, the single celled algae Nannochloropsis oculata, the macro algae Caulerpa taxifolia and multi-cellular higher plants Arabidopsis thaliana, Brassica rapa, Triticum durum and Ginkgo biloba. RESULTS: Using the plant model Arabidopsis thaliana, we identified a total of 39 highly methylated m(5)C sites in predicted structural positions of nuclear tRNAs and 7 m(5)C sites in rRNAs from nuclear, chloroplast and mitochondrial transcriptomes. Both the nucleotide position and percent methylation of tRNAs and rRNAs m(5)C sites were conserved across all species analysed, from single celled algae N. oculata to multicellular plants. Interestingly the mitochondrial and chloroplast encoded tRNAs were devoid of m(5)C in A. thaliana and this is generally conserved across Plantae. This suggests independent evolution of organelle methylation in animals and plants, as animal mitochondrial tRNAs have m(5)C sites. Here we characterize 5 members of the RNA 5-methylcytosine family in Arabidopsis and extend the functional characterization of TRDMT1 and NOP2A/OLI2. We demonstrate that nuclear tRNA methylation requires two evolutionarily conserved methyltransferases, TRDMT1 and TRM4B. trdmt1 trm4b double mutants are hypersensitive to the antibiotic hygromycin B, demonstrating the function of tRNA methylation in regulating translation. Additionally we demonstrate that nuclear large subunit 25S rRNA methylation requires the conserved RNA methyltransferase NSUN5. Our results also suggest functional redundancy of at least two of the NOP2 paralogs in Arabidopsis. CONCLUSIONS: Our data demonstrates widespread occurrence and conservation of non-coding RNA methylation in the kingdom Plantae, suggesting important and highly conserved roles of this post-transcriptional modification. PMID- 26268216 TI - The human papillomavirus (HPV) E7 protein antagonises an Imiquimod-induced inflammatory pathway in primary human keratinocytes. AB - High-risk human papillomaviruses (HPV) are the etiological pathogen of cervical and a number of ano-genital cancers. How HPVs overcome the significant barriers of the skin immune system has been the topic of intensive research. The E6 and E7 oncoproteins have emerged as key players in the deregulation of host innate immune pathways that are required for the recruitment of effector cells of the immune response. Here we demonstrate that E7, and to a lesser extend E6, strongly reduce NFkappaB activation in response to the inflammatory mediator imiquimod. Moreover, we establish that undifferentiated keratinocytes do not express the putative receptor for imiquimod, TLR7, and as such are stimulated by imiquimod through a novel pathway. Inhibition of imiquimod induced cytokine production required residues in the CR1 and CR3 regions of E7 and resulted in reduced nuclear translocation and acetylation of the p65 sub-unit of NFkappaB. The results provide further evidence for a TLR7-independent role of imiquimod in the epithelial immune response and reinforce the ability of the HPV oncoproteins to disrupt the innate immune response, which may have important consequences for establishment of a chronic infection. PMID- 26268217 TI - Efficacy of supraspinatus tendon repair using mesenchymal stem cells along with a collagen I scaffold. AB - OBJECTIVES: Our main objective was to biologically improve rotator cuff healing in an elderly rat model using mesenchymal stem cells (MSCs) in combination with a collagen membrane and compared against other current techniques. METHODS: A chronic rotator cuff tear injury model was developed by unilaterally detaching the supraspinatus (SP) tendons of Sprague-Dawley rats. At 1 month postinjury, the tears were repaired using one of the following techniques: (a) classical surgery using sutures (n = 12), (b) type I collagen membranes (n = 15), and (c) type I collagen membranes + 1 * 106 allogeneic MSCs (n = 14). Lesion restoration was evaluated at 1, 2, and 3 months postinjury based on biomechanical criteria. Continuous variables were described using mean and standard deviation (SD). To analyse the effect of the different surgical treatments in the repaired tendons' biomechanical capabilities (maximum load, stiffness, and deformity), a two-way ANOVA model was used, introducing an interaction between such factor and time (1, 2, and 3 months postinjury). RESULTS: With regard to maximum load, we observed an almost significant interaction between treatment and time (F = 2.62, df = 4, p = 0.053). When we analysed how this biomechanical capability changed with time for each treatment, we observed that repair with OrthADAPT and MSCs was associated with a significant increase in maximum load (p = 0.04) between months 1 and 3. On the other hand, when we compared the different treatments among themselves at different time points, we observed that the repair with OrthADAPT and MSCs has associated with a significant higher maximum load, when compared with the use of suture, but only at 3 months (p = 0.014). With regard to stiffness and deformity, no significant interaction was observed (F = 1.68, df = 4, p = 0.18; F = 0.40, df = 4, p = 0.81; respectively). CONCLUSIONS: The implantation of MSCs along with a collagen I scaffold into surgically created tendon defects is safe and effective. MSCs improved the tendon's maximum load over time, indicating that MSCs could help facilitate the dynamic process of tendon repair. PMID- 26268218 TI - Genetic characteristics of soybean resistance to HG type 0 and HG type 1.2.3.5.7 of the cyst nematode analyzed by genome-wide association mapping. AB - BACKGROUND: Soybean cyst nematode (SCN, Heterodera glycines Ichinohe) is one of the most fatal pests of soybean (Glycine max (L.) Merr.) worldwide and causes huge loss of soybean yield each year. Multiple sources of resistance are urgently needed for effective management of SCN via the development of resistant cultivars. The aim of the present study was to investigate the genetic architecture of resistance to SCN HG Type 0 (race 3) and HG Type 1.2.3.5.7 (race 4) in landraces and released elite soybean cultivars mostly from China. RESULTS: A total of 440 diverse soybean landraces and elite cultivars were screened for resistance to SCN HG Type 0 and HG Type 1.2.3.5.7. Exactly 131 new sources of SCN resistance were identified. Lines were genotyped by SNP markers detected by the Specific Locus Amplified Fragment Sequencing (SLAF-seq) approach. A total of 36,976 SNPs were identified with minor allele frequencies (MAF) > 4% that were present in 97% of all the genotypes. Genome-wide association mapping showed that a total of 19 association signals were significantly related to the resistance for the two HG Types. Of the 19 association signals, eight signals overlapped with reported QTL including Rhg1 and Rhg4 genes. Another eight were located in the linked regions encompassing known QTL. Three QTL were found that were not previously reported. The average value of female index (FI) of soybean accessions with resistant alleles was significantly lower than those with susceptible alleles for each peak SNP. Disease resistance proteins with leucine rich regions, cytochrome P450s, protein kinases, zinc finger domain proteins, RING domain proteins, MYB and WRKY transcription activation families were identified. Such proteins may participate in the resistant reaction to SCN and were frequently found in the tightly linked genomic regions of the peak SNPs. CONCLUSIONS: GWAS extended understanding of the genetic architecture of SCN resistance in multiple genetic backgrounds. Nineteen association signals were obtained for the resistance to the two Hg Types of SCN. The multiple beneficial alleles from resistant germplasm sources will be useful for the breeding of cultivars with improved resistance to SCN. Analysis of genes near association signals may facilitate the recognition of the causal gene(s) underlying SCN resistances. PMID- 26268220 TI - Use of Bristol Stool Form Scale to predict the adequacy of bowel preparation - a prospective study. AB - AIM: Inadequate bowel preparation continues to be a substantial problem for colonoscopy. The seven-point Bristol Stool Form Scale (BSFS) has been associated with delayed colonic transit in adults. We evaluated the utility of the BSFS to identify patients more likely to present with an inadequate preparation. METHOD: Two large community-based academic medical centres in New Jersey, USA, studied a prospective cohort of 411 consecutive patients undergoing outpatient colonoscopy who were prescribed similar bowel preparations. The BSFS and several other study variables were collected by gastroenterology fellows during an outpatient visit prior to scheduling colonoscopy. All colonoscopy examinations were performed in the morning by a gastroenterologist who graded the adequacy of bowel preparation. Inadequate preparation was defined as one resulting in a repeat colonoscopy at a shorter time interval than would generally be recommended based solely on risk factors or pathological findings. The ability of study variables to discriminate those who did or did not have an adequate preparation was summarized by the c statistic. The relationship between variables that provided some discrimination and the probability of an adequate preparation was modelled using logistic regression. RESULTS: The mean age of the study sample was 56 +/- 8 (SD) years and 63% were women. Bowel preparation was adequate in 337 (82%) of the patients. The BSFS ratings ranged from 1 to 7. The score was <3 in 144 (35%) indicating lower gastrointestinal motility. There was a statistically significant association between the score and the probability of an adequate bowel preparation (odds ratio 1.4; 95% confidence interval 1.2-1.7; P < 0.001) and the c-statistic was 0.64 (0.58-0.70). CONCLUSION: Use of the BSFS may help identify patients for whom standard bowel preparation most probably will not be adequate. PMID- 26268222 TI - Effects of coaching supervision, mentoring supervision and abusive supervision on talent development among trainee doctors in public hospitals: moderating role of clinical learning environment. AB - BACKGROUND: Effective talent development requires robust supervision. However, the effects of supervisory styles (coaching, mentoring and abusive supervision) on talent development and the moderating effects of clinical learning environment in the relationship between supervisory styles and talent development among public hospital trainee doctors have not been thoroughly researched. In this study, we aim to achieve the following, (1) identify the extent to which supervisory styles (coaching, mentoring and abusive supervision) can facilitate talent development among trainee doctors in public hospital and (2) examine whether coaching, mentoring and abusive supervision are moderated by clinical learning environment in predicting talent development among trainee doctors in public hospital. METHODS: A questionnaire-based critical survey was conducted among trainee doctors undergoing housemanship at six public hospitals in the Klang Valley, Malaysia. Prior permission was obtained from the Ministry of Health Malaysia to conduct the research in the identified public hospitals. The survey yielded 355 responses. The results were analysed using SPSS 20.0 and SEM with AMOS 20.0. RESULTS: The findings of this research indicate that coaching and mentoring supervision are positively associated with talent development, and that there is no significant relationship between abusive supervision and talent development. The findings also support the moderating role of clinical learning environment on the relationships between coaching supervision-talent development, mentoring supervision-talent development and abusive supervision-talent development among public hospital trainee doctors. Overall, the proposed model indicates a 26 % variance in talent development. CONCLUSION: This study provides an improved understanding on the role of the supervisory styles (coaching and mentoring supervision) on facilitating talent development among public hospital trainee doctors. Furthermore, this study extends the literature to better understand the effects of supervisory styles on trainee doctors' talent development are contigent on the trainee doctors' clinical learning environment. In summary, supervisors are stakeholders with the responsibility of facilitating learning conditions that hold sufficient structure and support to optimise the trainee doctors learning. PMID- 26268221 TI - A cluster randomised controlled trial and process evaluation of a training programme for mental health professionals to enhance user involvement in care planning in service users with severe mental health issues (EQUIP): study protocol for a randomised controlled trial. AB - BACKGROUND: Involving service users in planning their care is at the centre of policy initiatives to improve mental health care quality in England. Whilst users value care planning and want to be more involved in their own care, there is substantial empirical evidence that the majority of users are not fully involved in the care planning process. Our aim is to evaluate the effectiveness and cost effectiveness of training for mental health professionals in improving user involvement with the care planning processes. METHODS/DESIGN: This is a cluster randomised controlled trial of community mental health teams in NHS Trusts in England allocated either to a training intervention to improve user and carer involvement in care planning or control (no training and care planning as usual). We will evaluate the effectiveness of the training intervention using a mixed design, including a 'cluster cohort' sample, a 'cluster cross-sectional' sample and process evaluation. Service users will be recruited from the caseloads of care co-ordinators. The primary outcome will be change in self-reported involvement in care planning as measured by the validated Health Care Climate Questionnaire. Secondary outcomes include involvement in care planning, satisfaction with services, medication side-effects, recovery and hope, mental health symptoms, alliance/engagement, well-being and quality of life. Cost- effectiveness will also be measured. A process evaluation informed by implementation theory will be undertaken to assess the extent to which the training was implemented and to gauge sustainability beyond the time-frame of the trial. DISCUSSION: It is hoped that the trial will generate data to inform mental health care policy and practice on care planning. TRIAL REGISTRATION NUMBER: ISRCTN16488358 (14 May 2014). PMID- 26268223 TI - A PK-PD model of ketamine-induced high-frequency oscillations. AB - OBJECTIVE: Ketamine is a widely used drug with clinical and research applications, and also known to be used as a recreational drug. Ketamine produces conspicuous changes in the electrocorticographic (ECoG) signals observed both in humans and rodents. In rodents, the intracranial ECoG displays a high-frequency oscillation (HFO) which power is modulated nonlinearly by ketamine dose. Despite the widespread use of ketamine there is no model description of the relationship between the pharmacokinetic-pharmacodynamics (PK-PDs) of ketamine and the observed HFO power. APPROACH: In the present study, we developed a PK-PD model based on estimated ketamine concentration, its known pharmacological actions, and observed ECoG effects. The main pharmacological action of ketamine is antagonism of the NMDA receptor (NMDAR), which in rodents is accompanied by an HFO observed in the ECoG. At high doses, however, ketamine also acts at non-NMDAR sites, produces loss of consciousness, and the transient disappearance of the HFO. We propose a two-compartment PK model that represents the concentration of ketamine, and a PD model based in opposing effects of the NMDAR and non-NMDAR actions on the HFO power. MAIN RESULTS: We recorded ECoG from the cortex of rats after two doses of ketamine, and extracted the HFO power from the ECoG spectrograms. We fit the PK-PD model to the time course of the HFO power, and showed that the model reproduces the dose-dependent profile of the HFO power. The model provides good fits even in the presence of high variability in HFO power across animals. As expected, the model does not provide good fits to the HFO power after dosing the pure NMDAR antagonist MK-801. SIGNIFICANCE: Our study provides a simple model to relate the observed electrophysiological effects of ketamine to its actions at the molecular level at different concentrations. This will improve the study of ketamine and rodent models of schizophrenia to better understand the wide and divergent range of effects that ketamine has. PMID- 26268224 TI - Amplitude spectrum distance: measuring the global shape divergence of protein fragments. AB - BACKGROUND: In structural bioinformatics, there is an increasing interest in identifying and understanding the evolution of local protein structures regarded as key structural or functional protein building blocks. A central need is then to compare these, possibly short, fragments by measuring efficiently and accurately their (dis)similarity. Progress towards this goal has given rise to scores enabling to assess the strong similarity of fragments. Yet, there is still a lack of more progressive scores, with meaningful intermediate values, for the comparison, retrieval or clustering of distantly related fragments. RESULTS: We introduce here the Amplitude Spectrum Distance (ASD), a novel way of comparing protein fragments based on the discrete Fourier transform of their C(alpha) distance matrix. Defined as the distance between their amplitude spectra, ASD can be computed efficiently and provides a parameter-free measure of the global shape dissimilarity of two fragments. ASD inherits from nice theoretical properties, making it tolerant to shifts, insertions, deletions, circular permutations or sequence reversals while satisfying the triangle inequality. The practical interest of ASD with respect to RMSD, RMSDd, BC and TM scores is illustrated through zinc finger retrieval experiments and concrete structure examples. The benefits of ASD are also illustrated by two additional clustering experiments: domain linkers fragments and complementarity-determining regions of antibodies. CONCLUSIONS: Taking advantage of the Fourier transform to compare fragments at a global shape level, ASD is an objective and progressive measure taking into account the whole fragments. Its practical computation time and its properties make ASD particularly relevant for applications requiring meaningful measures on distantly related protein fragments, such as similar fragments retrieval asking for high recalls as shown in the experiments, or for any application taking also advantage of triangle inequality, such as fragments clustering. ASD program and source code are freely available at: http://www.irisa.fr/dyliss/public/ASD/. PMID- 26268225 TI - On-going malaria transmission in The Gambia despite high coverage of control interventions: a nationwide cross-sectional survey. AB - BACKGROUND: As indicators of burden of malaria have substantially decreased in The Gambia, reaching a pre-elimination status may be attainable. Achieving this goal requires in-depth understanding of the current burden of Plasmodium falciparum infection. METHODS: A nationwide cross-sectional survey was conducted in 2012 to determine the prevalence of P. falciparum infection, and to describe its heterogeneity and associated risk factors. Finger-prick blood samples were collected for microscopy, species-specific PCR and haemoglobin measurement. RESULTS: A total of 9,094 participants were included and median age was 11.9 years (IQR 5, 28). Overall prevalence of P. falciparum was 16.01 % with marked heterogeneity between sites (4.32-36.75 %) and within villages in each site (1.63 49.13 %). Across all sites, 51.17 % (745/1,456) of infections were asymptomatic and 35.61 % (448/1,258) were sub-microscopic. The odds of P. falciparum infection were higher in older children; 5-15 years (OR = 1.90; 95 % CI 1.60-2.26), adults (OR = 1.48; 95 % CI 1.24-1.78) and participants with moderate anaemia (OR = 1.62; 95 % CI 1.32-1.99). CONCLUSIONS: The current malaria control interventions are not sufficient to interrupt transmission in The Gambia as malaria prevalence is still relatively high in the eastern part of the country. New interventions aiming at interrupting transmission are needed and should be urgently evaluated. PMID- 26268226 TI - Bcl2 inhibition of mitochondrial DNA repair. AB - BACKGROUND: Accumulation of mitochondrial DNA (mtDNA) damage could enhance the frequency of mitochondrial mutations and promote a variety of mitochondria related diseases, including cancer. However, the mechanism(s) involved are not fully understood. METHODS: Quantitative extended length PCR was used to compare mtDNA and nDNA damage in human lung H1299 cells expressing WT Bcl2 or vector-only control. mtAPE1 endonuclease activity was analyzed by AP oligonucleotide assay. mtDNA mutation was measured by single molecule PCR. Subcellular localization of Bcl2 and APE1 was analyzed by subcellular fractionation. RESULTS: Bcl2, an anti apoptotic molecule and oncoprotein, effectively inhibits the endonuclease activity of mitochondrial APE1 (mtAPE1), leading to significant retardation of mtDNA repair and enhanced frequency of mtDNA mutations following exposure of cells to hydrogen peroxide (H2O2) or nitrosamine 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone (NNK, a carcinogen in cigarette smoke). Inversely, depletion of endogenous Bcl2 by RNA interference increases mtAPE1 endonuclease activity leading to accelerated mtDNA repair and decreased mtDNA mutation. Higher levels of mtAPE1 were observed in human lung cancer cells than in normal human bronchial epithelial cells (i.e. BEAS-2B). Bcl2 partially co-localizes with APE1 in the mitochondria of human lung cancer cells. Bcl2 directly interacts with mtAPE1 via its BH domains. Removal of any of the BH domains from Bcl2 abolishes Bcl2's capacity to interact with mtAPE1 as well as its inhibitory effects on mtAPE1 activity and mtDNA repair. CONCLUSIONS: Based our findings, we propose that Bcl2 suppression of mtDNA repair occurs through direct interaction with mtAPE1 and inhibition of its endonuclease activity in mitochondria, which may contribute to enhanced mtDNA mutations and carcinogenesis. PMID- 26268227 TI - Treating latent TB in primary care: a survey of enablers and barriers among UK General Practitioners. AB - BACKGROUND: Treating latent tuberculosis infection (LTBI) is an important public health intervention. In the UK, LTBI treatment is delivered in secondary care. Treating LTBI in the community would move care closer to home and could increase uptake and treatment completion rates. However, healthcare providers' views about the feasibility of this in the UK are unknown. This is the first study to investigate perceived barriers and enablers to primary care-based LTBI treatment among UK general practitioners (GPs). METHODS: A national survey amongst 140 randomly sampled UK GPs practising in areas of high TB incidence was performed. GPs' experience and perceived confidence, barriers and enablers of primary care based LTBI treatment were explored and multivariable logistic regression was used to determine whether these were associated with a GP's willingness to deliver LTBI treatment. RESULTS: One hundred and twelve (80 %) GPs responded. Ninety three (83 %; 95 % CI 75 %-89 %) GPs said they would be willing to deliver LTBI treatment in primary care, if key perceived barriers were addressed during service development. The major perceived barriers to delivering primary care based LTBI treatment were insufficient experience among GPs of screening and treating LTBI, lack of timely specialist support and lack of allied healthcare staff. In addition, GPs felt that appropriate resourcing was key to the successful and sustainable delivery of the service. GPs who reported previous experience of screening or treatment of patients with active or latent TB were almost ten times more likely to be willing to deliver LTBI treatment in primary care compared to GPs with no experience (OR: 9.98; 95 % CI 1.22-81.51). CONCLUSIONS: UK GPs support primary care-based LTBI treatment, provided they are given appropriate training, specialist support, staffing and financing. PMID- 26268228 TI - Analysis of cerebrospinal fluid from cattle with central nervous system disorders after storage for 24 hours with autologous serum. AB - BACKGROUND: We compared the changes in cell morphology, total and differential cell counts between cerebrospinal fluid (CSF) samples analyzed within an hour of collection (fresh sample) and after the addition of autologous serum and storage for 24 h (stored sample) in 27 cattle with central nervous system disorders. RESULTS: There was a positive linear correlation between total and differential cell counts in the fresh and the stored samples. Cell morphology was preserved in all stored samples, except for increased vacuolization of mononuclear cells and cleaved nuclei of some small mononuclear cells. In the stored CSF samples, the total nucleated cell count and monocyte percentage were decreased (P = 0.01; P = 0.03), while the lymphocyte percentage was increased (P = 0.04). Mononuclear pleocytosis diagnosed in 20 fresh samples was cytologically confirmed in 12 of the 20 stored samples. In the remaining eight stored samples, the number of total nucleated cells was within the normal range. Neutrophilic pleocytosis was confirmed in all seven stored samples. The overall agreement rate between cytologic interpretation of the fresh and the stored CSF samples was 70 % (100 % for neutrophilic pleocytosis and 60 % for mononuclear pleocytosis). CONCLUSIONS: Adding 11 % of autologous serum to CSF samples might allow delayed analysis with a good agreement rate for CSF cytological interpretation. Caution is nonetheless warranted, as animal age, anamnesis, and neurological presentation need to be considered when interpreting stored CSF without pleocytosis. PMID- 26268229 TI - [CT screening on lung cancer: true or false]. PMID- 26268230 TI - [The management of pulmonary nodules]. PMID- 26268231 TI - [Prognostic factors and response of chemotherapy including amrubicin in small cell lung cancer patients]. AB - OBJECTIVE: To evaluate the response, toxicity and prognostic factors of amrubicin in the therapy of small cell lung cancer (SCLC). METHODS: Thirty-one SCLC patients treated with amrubicin in Beijing Cancer Hospital from Dec.2008 to Apr.2013, including 21 males and 10 females, aged from 32 to 75 years, were enrolled in this study. Amrubicin was injected intravenously with 40 mg/m2 d1-3, Q21 d or combined with cisplatin 60 mg/m2 d1, Q 21 d. The first line chemotherapy regimens included amrubicin plus cisplatin in 11 cases, etopside plus platin in 18 cases and other drugs in 2 cases. The second and more line chemotherapy treatments included amrubicin in 20 cases, topotican in 14 cases and others in 28 cases. SPSS 16.0 statistical analysis software was used to analyze the clinical characteristics and survivals. RESULTS: The median progression free survival (PFS) of patients receiving amrubicin plus cisplatin and single amrubicin were 7.5 months (95% CI: 6.2 to 8.8 ) and 4.1 months (95% CI:1.2 to 7.0) respectively (P= 0.090). There were 16 refractory patients whose disease progressed within 3 months after first line chemotherapy and 15 sensitive patients who had tumor progression after more than 3 months; the median survival time (MST) were 14.2 months (95% CI 11.1-17.3) and 21.3 months (95% CI 15.7-26.9) respectively (P= 0.018). Patients treated with amrubicin plus cisplatin as first line therapy had a prolonged median PFS compared with etopside plus platin, which were 7.5 months (95% CI:6.2-8.8) vs. 4.6 months (95% CI:1.7-7.5) (P= 0.055). Patients received amrubicin, topotican or other drugs as second or more line therapy had median PFS of 4.1 months (95% CI: 1.2-7.0), 1.4 months (95% CI: 0.8-2.0) and 1.6 months (95% CI:1.2-1.9) respectively (P= 0.013), while the median PFS was 5.6 months (95% CI: 2.0-9.2), 1.4 months (95% CI: 0.6-2.2) and 1.4 months (95% CI: 0.8-2.0) (P= 0.005 and 0.003) in refractory patients. CONCLUSIONS: Amrubicin as second or more line treatment was shown to be an effective and safe drug for SCLC patients with a significant survival benefit compared with other drugs, especially in refractory patients. It suggested that amrubicin might be one of the preferred therapies for refractory SCLC. PMID- 26268232 TI - [Effects of 17-AAG on the proliferation and apoptosis of human lung cancer A549 and H446 cells]. AB - OBJECTIVE: To observe the effect of 17-(allylamino)-17-demethoxygeldanamycin (17 AAG) on the apoptosis of human lung cancer cell lines A549 and H446, and to investigate the potential mechanisms. METHODS: Proliferation inhibition and apoptosis assays, and the cell cycles were detected by MTT and flow cytometry respectively. Western blot was used to determine the expression level of proteins such as Hsp90, Hsp70, AKt, Her-2, Bcl-2 and Bax. RESULTS: After treated with 17 AAG, the proliferation of both A549 and H446 cells was inhibited significantly in a dose-dependent manner; as the concentration of 17-AAG was from 50 to 500 nmol/L, the IC50 values to A549 and H446 cell lines were (222 +/- 13) nmol/L and (189 +/- 7) nmol/L respectively at 48 h. Cell cycle assays showed that 17-AAG was able to arrest cell cycles of A549 and H446 cell lines at the G2/M phase. Apoptosis assay showed that 17-AAG was capable of inducing apoptosis in A549 and H446 cell lines. After treated with 17-AAG for 48 h, there were significant differences between the 400 nmol/L groups(46.3% for A549 cell line and 56.9% for H446 cell line) and the control group (11.9% for A549 cell line and 6.9% for H446 cell line, P < 0.01). Western blot results showed that the relative proteins of the Hsp90 signal pathway in both A549 and H446 cell lines underwent similar changes after 17-AAG treatment: Akt and Her-2 decreased significantly while the expression of Hsp70 increased. Meanwhile, the expression of Bcl-2 decreased but that of Bax increased, indicating that 17-AAG was able to promote apoptosis mode in A549 and H446 cells. CONCLUSIONS: 17-AAG can regulate the expression level of apoptosis-related proteins such as Bax and Bcl-2 by Hsp90 signaling pathway in A549 and H446 cells, and ultimately inhibit cell proliferation and induce apoptosis. PMID- 26268233 TI - [Efficacy and safety of delayed thrombolytic therapy for acute massive pulmonary throboembolism]. AB - OBJECTIVE: To observe the efficacy and safety of delayed thrombolytic therapy on acute massive pulmonary thromboembolism (PTE) and discuss the influence factors. METHODS: From 2009 to 2013, the clinical data of patients with acute massive pulmonary thromboembolism were analyzed retrospectively. Patients with over 14 day duration and treated with thrombolytic therapy (delayed thrombolytic group) were compared with those within 14-day duration and treated with thrombolytic therapy (normal thrombolytic group) in the same period. General conditions before treatment, case history, efficacy and the incidence of bleeding after one-week treatment were collected. The influence factors of delayed thrombolytic therapy were analyzed. RESULTS: Sixty two cases were collected and divided into the normal thrombolytic group with 32 cases and the delayed thrombolytic group with 30 cases. Compared with the normal thrombolytic group, the delayed thrombolytic group had a longer duration [(24.8 +/- 0.9) vs.(7.2 +/- 0.6)d, P<0.001], an aggravation time of (5.3 +/- 0.8) d, and higher systolic pulmonary arterial pressure (SPAP) [(69 +/- 4)vs. (55 +/- 4)mmHg, 1 mmHg= 0.133 kPa, P= 0.016]. Ages, genders, D-Dimmer, CT subpulmonic obstruction index (CTI), brain natriuretic peptide (BNP), cardiactroponinI (TnI), PaCO2values and PaO2values had no statistical difference between two groups. After one-week treatment, the efficacy and the incidence of bleeding was 78% and 25% respectively in normal thrombolytic group, while they were 77% and 30% respectively in delayed thrombolytic group, and there was no significant difference between two groups (P>0.05). The single factor analysis showed that the delayed thrombolytic group had more patients with hypertension, were older and had a lower PaO2(P<0.05 or 0.01). Multivariate logistic regression analysis did not find the predictors of delayed thrombolytic therapy (P>0.05). CONCLUSIONS: For acute massive PTE patients with duration over 14 days, increased D-D and new exacerbation of symptoms,delayed thrombolytic therapy had the same efficacy with the normal thrombolytic therapy. The factors for predicting efficacy need further research. PMID- 26268234 TI - [Evaluation of a mouse model of chronic obstructive pulmonary disease induced by intraperitoneal injections of cigarette smoke extract]. AB - OBJECTIVE: To evaluate a mouse model of chronic obstructive pulmonary disease (COPD) induced by intraperitoneal injections of cigarette smoke extract (CSE), and to study the potential mechanisms. METHODS: Mice were injected intraperitoneally with CSE at different time points to establish a mouse model of COPD. Mouse lung mechanics parameters were measured, and the total numbers and differentials of cells in bronchoalveolar lavage fluid (BALF) were counted. Pathological changes of lung tissue were observed and mean linear intercept (MLI) and alveolar destructive index (DI) were measured. The expressions of matrix metalloproteinases-12(MMP12), neutrophil elastase (NE),tissue inhibitor of metalloproteinase-1(TIMP1), pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL 6), Th1 cytokines (IFN-gamma), Th2 cytokines (IL-5, IL-13) and the neutrophil chemokine KC were determined in the lungs of all mice. RESULTS: Significant increase of total lung capacity(TLC) [(0.73 +/- 0.02), (0.83 +/- 0.04), (0.97 +/- 0.02)ml] was found in the CSE group as compared with the PBS control group [(0.65 +/- 0.01), (0.67 +/- 0.02), (0.71 +/- 0.04)ml, t= 4.109, 3.666, 5.994, P<0.01] at day 21, 41, 61. Lung compliance was higher in the CSE group [(0.041 +/- 0.002) ml/cmH2O (1 cmH2O= 0.098 kPa), (0.039 +/- 0.001) ml/cmH2O] than the PBS control group [(0.030 +/- 0.001) ml/cmH2O, (0.032 +/- 0.003) ml/cmH2O, t= 4.788,2.508, P<0.05] at day 41,61, but airway resistance in the lungs (R) was lower in the CSE group [(0.959 +/- 0.016) cmH2O.s.ml-1, (0.976+/-0.020) cmH2O.s.ml-1] than the PBS control group [(1.043 +/- 0.022) cmH2O.s.ml(-1), (1.085+/-0.043) cmH2O.s.ml-1] (t= 2.928,2.321, P<0.05). The total numbers of BALF cells in the CSE group [(23.83 +/- 2.63)*104, (20.67+/-1.69)*104, (18.67+/-1.56) * 104] were increased compared with the PBS control group [(7.33 +/- 0.61)*104, (7.67 +/- 0.76)*104, (6.67 +/- 0.88)*104, t= 6.119,7.027,6.685,P<0.01] at day 21,41,61, predominantly with neutrophils and macrophages. Typical COPD pathological changes of lung tissue were evident, including Inflammatory cell infiltration in the lung parenchyma and increased mean linear intercept (MLI) in the CSE group [(48.0 +/- 1.4), (56.1 +/- 2.4), (59.3 +/- 3.3)um] as compared with the PBS control group [(40.5 +/- 1.2), (43.7 +/- 1.2), (43.5 +/- 1.2)um, t= 4.015,4.695,4.612, P<0.01] as well as increased alveolar destructive index (DI) in the CSE group [(15.2 +/- 1.3)%, (22.4 +/- 1.3)%, (23.8 +/- 1.0)%] as compared with the PBS control group [(11.1 +/- 0.9)%, (10.8 +/- 1.0)%, (12.4 +/- 0.7)%,t= 2.532, 7.225, 8.471, P < 0.05] at the 3 time points. The expressions of MMP12 and NE increased significantly in the CSE-treated mice. Pro-inflammatory cytokines (TNF-alpha, IL 1beta, L-6), Th1 cytokine IFN-gamma and KC all increased significantly in the CSE treated mice as compared with the PBS-control mice. CONCLUSIONS: A mouse model of COPD was successfully established by repeated intraperitoneal injections of CSE in a shorter period of time. Local inflammation and proteinase/anti-proteinase imbalance as a result of CSE-induced immunological responses may be the underlying mechanisms. PMID- 26268235 TI - [Transbronchoscopic end-tidal carbon dioxide detection for location of the leading bronchus in patients with pneumothorax]. AB - OBJECTIVE: To evaluate the effect of end-tidal carbon dioxide (EtCO2) detection for location of the leading bronchus in patients with pneumothorax. METHODS: Transbronchoscopic EtCO2 detection was performed in 4 patients with intractable pneumothorax in whom transbronchoscopic balloon detection failed to localize the leading bronchus. A specific bronchus was suspected to be the leading bronchus when its EtCO2 value was significantly lower than that of the main bronchus of the affected lung. After the pleural air leakage was successfully sealed by bronchial occlusion of the suspected bronchus, the EtCO2 was confirmed to indicate the leading bronchus. RESULTS: Transbronchoscopic EtCO2 detection successfully located the leading bronchus in all 4 patients. CONCLUSIONS: Transbronchoscopic EtCO2 detection is a new method of locating the leading bronchus in patients with intractable pneumothorax. PMID- 26268236 TI - [The effect of MTB antigens on the NFAT5 expression in monocytes from human peripheral blood]. AB - OBJECTIVE: To study the effect of Mycobacterium tuberculosis antigens early secretory antigen target 6/culture filtrate protein 10 (ESAT-6/CFP-10) on nuclear factor of activated T-cells 5 (NFAT5) mRNA in monocytes from human peripheral blood. METHODS: Fifteen patients with active pulmonary tuberculosis (age range: 33-42 y, mean: 37 y, male/female: 9/6) were recruited from the Institute of Tuberculosis in 309 Hospital, and 15 healthy subjects (age range: 37-42 y, mean: 40 y, male/female: 9/6) were recruited from Medical Examination Center of the hospital. Monocytes were isolated from peripheral blood and stimulated with whole cell lysate of H37Rv strain and peptide pool of ESAT-6/CFP-10. Fluorescence quantitative PCR was used to detect the mRNA expression of NFAT5, and differences of NFAT5 mRNA between unstimulated and stimulated monocytes were analyzed by paired t test statistic method. RESULTS: The expression of NFAT5 mRNA in monocytes from patients with active pulmonary tuberculosis was significantly decreased when stimulated with peptide pool of ESAT-6/CFP-10 compared with unstimulated monocytes (0.18 +/- 0.12 vs. 0.23 +/- 0.15) (t = 2.591, P < 0.05). Similarly, the expression of NFAT5 mRNA in monocytes from healthy subjects was also significantly decreased when stimulated with peptide pool of ESAT-6/CFP-10 compared with unstimulated monocytes (0.17 +/- 0.09 vs 0.21 +/- 0.09) (t = 2.828, P < 0.05). However, the expression of NFAT5 mRNA in monocytes stimulated with whole cell lysate was not significantly changed (t = 1.142, P > 0.05), which was 0.28 +/- 0.25 and 0.23 +/- 0.15 in stimulated and unstimulated monocytes, respectively. Similarly, the expression of NFAT5 mRNA in monocytes from healthy subjects was also not significantly changed when stimulated with whole cell lysate (t = 0.451 9, P > 0.05), which was 0.20 +/- 0.12 and 0.21 +/- 0.09 in stimulated and unstimulated monocytes, respectively. CONCLUSIONS: The MTB antigen ESAT-6/CFP-10 can inhibit NFAT5 expression in human monocytes in vitro. PMID- 26268237 TI - [Outbreak of six cases of nosocomial Legionella pneumophila pneumonia]. AB - OBJECTIVES: To describe the clinical characteristics, diagnosis, treatment and the causes of outbreak of nosocomial pneumonia due to Legionella pneumophila. METHODS: The medical records of 6 cases of nosocomial Legionella pneumophila pneumonia were retrospectively reviewed, and the clinical data of clinical presentation, treatment, and etiologic diagnosis were analyzed. RESULTS: The 6 patients were health care providers of the Department of Respiratory and Critical Care Medicine of the Affiliated Hospital of Logistics University of PAPF. There were 5 female and 1 male patients, aged 23 to 27 years. The diagnosis of Legionella pneumonia was made based on a positive Legionella urinary I antigen test. In all the 6 cases, the disease was attributable to inhaling contaminated aerosols produced by the air conditioning system in our hospital. All the 6 patients presented with fever of 37.5-39 degrees C, and productive cough. One patient had anorexia, dyspnoea, and pleuritic chest pain, while headache was reported in 3 patients. Physical examinations revealed lung rales in 3 patients. Single or multiple patchy infiltrates were found on Chest CT in all patients. However, the typical extrapulmonary manifestations of Legionnaires' disease, including relative bradycardia, hyponatremia, hypophosphatemia and diarrhea, were not present in the 6 patients. Neither neurological abnormalities nor renal involvement were observed. CONCLUSIONS: Our data demonstrated that Legionella pneumonia may be mild with atypical laboratory findings and clinical manifestations, with fever, cough, chest tightness, headache, etc. The radiologic manifestations of Legionella pneumonia were single or multiple patchy infiltrates, similar to those of viral pneumonia, and therefore their differential diagnosis was needed. Legionella pneumophila can outbreak through the respiratory tract, in public places with central air-conditioning system, hot water piping systems and hospitals, and therefore microbiological monitoring, cleaning and disinfection of the water system was required for prevention of the outbreaks of Legionnaires' disease. PMID- 26268239 TI - [Progress on pneumonia caused by streptococcus viridans group]. PMID- 26268238 TI - [Diagnosis of pulmonary ground-glass lesions]. PMID- 26268240 TI - [A new therapy for asthma: bronchial thermoplasty]. PMID- 26268242 TI - The pigment characteristics and productivity shifting in high cell density culture of Monascus anka mycelia. AB - BACKGROUND: Monascus mycelia and pigments are promising sources of food and medicine with their potential pharmaceutical values and health-improving functions. Using high cell density fermentation of Monascus spp. to achieve higher mycelium and yellow pigment production is worthy to be researched. In this study, the characteristics and productivity shifting of pigments in high cell density culture of Monascus anka GIM 3.592 were investigated. RESULTS: The high yield of Monascus mycelia up to 39.77 g/L dry cell weight (DCW), which was achieved by fed-batch fermentation with the feeding medium containing C, N, P and trace elements, was four times higher than that of conventional batch culture. But the total pigment production decreased by 14.6 %, which suggested non-coupled growth. Potential novel yellow pigments accumulated constantly at the late stage of the fed-batch culture, which resulted in a shift in pigment characteristics so that yellow pigments became the dominant pigments. Citrinin production was extremely low and independent of feeding ingredients. CONCLUSIONS: This study provided a suitable fermentation strategy to produce functional Monascus mycelia with a high proportion of yellow pigments in high cell density culture. For the first time, it reported the pigment productivity and characteristics shifting in high cell density culture of Monascus. PMID- 26268241 TI - IDH2R172 mutations define a unique subgroup of patients with angioimmunoblastic T cell lymphoma. AB - Angioimmunoblastic T-cell lymphoma (AITL) is a common subtype of peripheral T cell lymphoma (PTCL) with a poor prognosis. We performed targeted resequencing on 92 cases of PTCL and identified frequent mutations affecting RHOA, TET2, DNMT3A, and isocitrate dehydrogenase 2 (IDH2). Although IDH2 mutations are largely confined to AITL, mutations of the other 3 can be found in other types of PTCL, although at lower frequencies. These findings indicate a key role of epigenetic regulation in the pathogenesis of AITL. However, the epigenetic alterations induced by these mutations and their role in AITL pathogenesis are still largely unknown. We correlated mutational status with gene expression and global DNA methylation changes in AITL. Strikingly, AITL cases with IDH2(R172) mutations demonstrated a distinct gene expression signature characterized by downregulation of genes associated with TH1 differentiation (eg, STAT1 and IFNG) and a striking enrichment of an interleukin 12-induced gene signature. Ectopic expression of IDH2(R172K) in the Jurkat cell line and CD4(+) T cells led to markedly increased levels of 2-hydroxyglutarate, histone-3 lysine methylation, and 5-methylcytosine and a decrease of 5-hydroxymethylcytosine. Correspondingly, clinical samples with IDH2 mutations displayed a prominent increase in H3K27me3 and DNA hypermethylation of gene promoters. Integrative analysis of gene expression and promoter methylation revealed recurrently hypermethylated genes involved in T cell receptor signaling and T-cell differentiation that likely contribute to lymphomagenesis in AITL. PMID- 26268244 TI - Predictors of Posttraumatic Stress Symptom Trajectories in Parents of Children Exposed to Motor Vehicle Collisions. AB - OBJECTIVE: Following child trauma, parents are at risk of developing posttraumatic stress disorder (PTSD), either owing to their direct involvement or from hearing of their child's involvement. Despite the potential impact of a parent's development of PTSD on both the parent and child, little is known about what may place a parent at increased risk. METHOD: PTSD symptoms were assessed <= 4 weeks, 6 months, and 3 years post-trauma, along with a range of potential risk factors, in a sample of parents of 2-10-year-old children who were involved in a motor vehicle collision. RESULTS AND CONCLUSIONS: Two symptom trajectories were identified: Those parents whose symptoms remained low across all time points and those whose symptoms remained elevated at 6 months post-trauma and declined by 3 years. Subjective threat, thought suppression, and maladaptive cognitions about damage to the child were identified as key predictors of poorer outcomes. PMID- 26268243 TI - XWAS: A Software Toolset for Genetic Data Analysis and Association Studies of the X Chromosome. AB - XWAS is a new software suite for the analysis of the X chromosome in association studies and similar genetic studies. The X chromosome plays an important role in human disease and traits of many species, especially those with sexually dimorphic characteristics. Special attention needs to be given to its analysis due to the unique inheritance pattern, which leads to analytical complications that have resulted in the majority of genome-wide association studies (GWAS) either not considering X or mishandling it with toolsets that had been designed for non-sex chromosomes. We hence developed XWAS to fill the need for tools that are specially designed for analysis of X. Following extensive, stringent, and X specific quality control, XWAS offers an array of statistical tests of association, including: 1) the standard test between a SNP (single nucleotide polymorphism) and disease risk, including after first stratifying individuals by sex, 2) a test for a differential effect of a SNP on disease between males and females, 3) motivated by X-inactivation, a test for higher variance of a trait in heterozygous females as compared with homozygous females, and 4) for all tests, a version that allows for combining evidence from all SNPs across a gene. We applied the toolset analysis pipeline to 16 GWAS datasets of immune-related disorders and 7 risk factors of coronary artery disease, and discovered several new X-linked genetic associations. XWAS will provide the tools and incentive for others to incorporate the X chromosome into GWAS and similar studies in any species with an XX/XY system, hence enabling discoveries of novel loci implicated in many diseases and in their sexual dimorphism. PMID- 26268245 TI - Splicing Machinery Facilitates Post-Transcriptional Regulation by FBFs and Other RNA-Binding Proteins in Caenorhabditis elegans Germline. AB - Genetic interaction screens are an important approach for understanding complex regulatory networks governing development. We used a genetic interaction screen to identify cofactors of FBF-1 and FBF-2, RNA-binding proteins that regulate germline stem cell proliferation in Caenorhabditis elegans. We found that components of splicing machinery contribute to FBF activity as splicing factor knockdowns enhance sterility of fbf-1 and fbf-2 single mutants. This sterility phenocopied multiple aspects of loss of fbf function, suggesting that splicing factors contribute to stem cell maintenance. However, previous reports indicate that splicing factors instead promote the opposite cell fate, namely, differentiation. We explain this discrepancy by proposing that splicing factors facilitate overall RNA regulation in the germline. Indeed, we find that loss of splicing factors produces synthetic phenotypes with a mutation in another RNA regulator, FOG-1, but not with a mutation in a gene unrelated to posttranscriptional regulation (dhc-1). We conclude that inefficient pre-mRNA splicing may interfere with multiple posttranscriptional regulatory events, which has to be considered when interpreting results of genetic interaction screens. PMID- 26268246 TI - Activation of EZH2 and SUZ12 Regulated by E2F1 Predicts the Disease Progression and Aggressive Characteristics of Bladder Cancer. AB - PURPOSE: Previous study identified E2F1 as a key mediator of non-muscle-invasive bladder cancer (NMIBC) progression. The aim of this study was to identify the E2F1-related genes associated with poor prognosis and aggressive characteristics of bladder cancer. EXPERIMENTAL DESIGN: Microarray analysis was performed to find E2F1-related genes associated with tumor progression and aggressiveness in the gene expression data from 165 primary patients with bladder cancer. The biologic activity of E2F1-related genes in tumor progression and aggressiveness was confirmed with experimental assays using bladder cancer cells and tumor xenograft assay. RESULTS: The expression of E2F1 was significantly associated with EZH2 and SUZ12. The overexpression of E2F1, EZH2, and SUZ12 enhanced cancer progression including cell colony formation, migration, and invasiveness. Knockdown of these genes reduced motility, blocked invasion, and decreased tumor size in vivo. E2F1 bound the proximal EZH2 and SUZ12 promoter to activate transcription, suggesting that E2F1 and its downstream effectors, EZH2 and SUZ12, could be important mediators for the cancer progression. In addition, we confirmed an association between these genes and aggressive characteristics. Interestingly, the treatment of anticancer drugs to the cells overexpressing E2F1, EZH2, and SUZ12 induced the expression of CD44, KLF4, OCT4, and ABCG2 known as cancer stem cell (CSC)-related genes. CONCLUSIONS: The link between E2F1, EZH2, and/or SUZ12 revealed that E2f1 directly regulates transcription of the EZH2 and SUZ12 genes. The signature of E2F1-EZH2-SUZ12 shows a predictive value for prognosis in bladder tumors and the E2F1-EZH2-SUZ12-driven transcriptional events may regulate the cancer aggressiveness and chemo-resistance, which may provide opportunity for development of new treatment modalities. PMID- 26268248 TI - India cancels trade talks after Europe bans 700 generic drugs. PMID- 26268247 TI - Impaired GAPDH-induced mitophagy contributes to the pathology of Huntington's disease. AB - Mitochondrial dysfunction is implicated in multiple neurodegenerative diseases. In order to maintain a healthy population of functional mitochondria in cells, defective mitochondria must be properly eliminated by lysosomal machinery in a process referred to as mitophagy. Here, we uncover a new molecular mechanism underlying mitophagy driven by glyceraldehyde-3-phosphate dehydrogenase (GAPDH) under the pathological condition of Huntington's disease (HD) caused by expansion of polyglutamine repeats. Expression of expanded polyglutamine tracts catalytically inactivates GAPDH (iGAPDH), which triggers its selective association with damaged mitochondria in several cell culture models of HD. Through this mechanism, iGAPDH serves as a signaling molecule to induce direct engulfment of damaged mitochondria into lysosomes (micro-mitophagy). However, abnormal interaction of mitochondrial GAPDH with long polyglutamine tracts stalled GAPDH-mediated mitophagy, leading to accumulation of damaged mitochondria, and increased cell death. We further demonstrated that overexpression of inactive GAPDH rescues this blunted process and enhances mitochondrial function and cell survival, indicating a role for GAPDH-driven mitophagy in the pathology of HD. PMID- 26268249 TI - A commercial human protamine-2 antibody used in several studies to detect mouse protamine-2 recognizes mouse transition protein-2 but not protamine-2. AB - The exchange of histones for transition proteins (TNPs) and finally protamines is an essential process during spermatogenesis that enables the strong condensation of chromatin during sperm formation. Research on this process obviously depends on the availability of specific antibodies recognizing these nuclear proteins. A commercial antibody generated against human protamine-2 (PRM2) has been described to cross-react with mouse PRM2 and in fact has been used in several studies to detect mouse PRM2. Some inconsistent results obtained with this goat-derived antibody prompted us to re-examine its specificity. In immunofluorescence experiments with epididymal sperm, only a low percentage of sperm nuclei were stained by this antibody, whereas a mouse monoclonal anti- PRM2 antibody stained most sperm, as expected. Western blot analysis of basic nuclear proteins from spermatids and sperm separated by acid urea (AU) gel electrophoresis revealed that the goat anti- PRM2 antiserum binds to mouse TNP2 but not mouse PRM2. Epitope mapping using glutathione-S-transferase-fusion proteins with peptide sequences conserved in human PRM2 and mouse TNP2 identified the tetrapeptide arginyl-lysyl-arginyl-threonine as an epitope of the goat anti- PRM2 antiserum. Our findings underline the importance of using AU gel electrophoresis to confirm specificities of antibodies directed against basic nuclear proteins, which are not well separated, and may show abnormal migration behaviour, in SDS polyacrylamide gel electrophoresis. PMID- 26268250 TI - [Experience of treatment and understanding of impediment disease in Shen nong ben cao jing (Shen-ntonz's Classic of Materia Medica)]. AB - As a book with significant historical materials for the research of impediment disease not to be ignored, Shen nong ben cao jing (Shennong's Classic of Materia Medica) contains, among its 365 kinds of materia medica, 75 kinds of medicines related to impediment disease. Among the latter ones, 51 are related to "damp impediment", "cold-damp impediment", "wind-cold-damp impediment", "wind impediment", "wind-damp impediment", and "cold impediment"; 16 are related to "laryngeal impediment", "general impediment", and "blood impediment"; 8 are related to "muscular impediment", "stomach impediment", "hernia-conglomeration impediment", "internal consumptive-thirst impediment", "wilting impediment", and "hemiplegic impediment". To systematically analyze the properties, tastes, and effects of these medicines and its related knowledge, and then further explore the overall recognition and their treating experience of the physicians at that period would not only enrich the historical research on impediment disease, but also offer much help and reference to the understanding and treatment of impediment for contemporary clinicians. PMID- 26268251 TI - [Textual research on Amara (Mangifera Indica Linn), Butea monsperma (Lam) Kuntze, and Ferula asatoitida L]. AB - In the Buddhist canons, there are lots of medicines imported from abroad recorded. The dictionary works of such Buddhist canons give detailed annotations and explanations to all these foreign medicines, from which we can investigate the features of all these medicines. It is also clear that these three medicines were imported into China no later than the Tang Dynasty. Amara was originally grown in the xi yu (Western Region) , now called Mango. Its form and connotation appeared no later than the eastern Han Dynasty, and the explanation of this medicine appears in the A Great Modern Dictionary of Chinese is wrong. While its explanation for Butea monsperma should be supplemented. There are two kinds of asafoitida, herbaceous and woody. Only the former one is used for medical purpose, and the annotation appeared in A Great Modern Dictionary of Chinese is problematic. PMID- 26268252 TI - [The campaign of returning to the ancient in sphygmology in the Republican Period as viewed from Mai xue cong shu (Series of Pulse Taking)]. AB - From the Southern and Northern Dynasties to the beginning of the Northern Song Dynasty, the models of "master and apprentice" and "physician of long family tradition for generations" were the main ways for teaching medical knowledge. With the rapid amassment of medical books in the Due to the rapid transmission of western science and technology into China in the Republican period, the art of pulse taking had been treated as unscientific. Yao Xinyuan advocated the recovery of ancient pulse taking of the three-portion approach, i.e., taking the pulses at the neck, hands, and feet for comparison. To spread this idea, Yao and Zhang Ziying compiled the Mai xue cong shu (Series of Pulse Taking) in 1937-1947. Altogether 4 issues were published carrying 29 articles concerning the theoretical exploration, experimental research, and clinical practice. Their thinking and approaches were influential to the study and development of modern sphygmology. PMID- 26268253 TI - [Research on China railway health campaign in 1930s]. AB - The motivation factors of China's railway health campaign in 1930s included avocation by the government, mass media mobilization, railway authorities' hygiene awareness and the systematization of the construction of organization. During the health campaign, the railway authorities adopted various approaches for its formation, including the rally speeches, distribution of materials, cleaning and vaccination etc. Unfortunately, the actual effect of railway health campaign was not satisfactory, yet, it enhanced theoretically railway employees' health knowledge and contributed to the promotion of modernization of hygienic knowledge. Meanwhile, there still existed many problems in the railway health campaign, for example, lack of funds, formalism and uneven development among the railway bureaus. PMID- 26268254 TI - [Analysis of Peng Zemin's medical letter]. AB - Mr. Peng Zemin, a senior leader of the Kuomintang leftist and patriotic overseas Chinese, had acknowledged the famous Guangdong modern TCM masters Chen Botan as his mentor in TCM for six years, and deeply affected by Chen Botan's way of prescribing large dose of classical recipes. Guang-dong Chinese Medicine Museum has collected a number of Mr. Peng Zernin' s letters, which were handwriting works written by Mr. Peng Zemin himself to his nephew Peng Bingtang who worked in the government of Guyang Wulanchabu League, Inner Mongolia. Among them, nine are related to medicine, reflecting Mr. Peng Zemin' s medical activities, medical ethics and medical practice experience, the way he prescribed after Chen Botan's characteristics of prescribing and applying materia medica. PMID- 26268255 TI - [Analytical research on Zheng Hao's Participation of the International Congress of Leprosy in 1909]. AB - The Second International Congress was held in August, 1909 in Norway. Zheng Hao was dispatched by the Qing Government to attend the Congress as a representative. Through the Congress, Chinese people got to understand the latest ideas of prevention and treatment of leprosy in international medical field, and the approaches they adopted as well at that time. Meanwhile, Zheng Hao frankly confessed the backward status on the prevention and treatment in leprosy in China, and expressed the strong will to learn from the western world in this regard. This historical event, commonly ignored, manifested the fact that, beginning from the late Qing Dynasty, the involvement of Chinese medicine into the world medical trend as a whole was proceeding. By seizing this rare chance of participating the international meeting, the outstanding Chinese medical persons, with Zheng Hao as its representative, made up their mind to keep up with the international medical advanced pace, learning lessons, and pushing forward the development of Chinese medicine. PMID- 26268256 TI - [Endocrine therapy for breast cancer: past and present]. AB - The endocrine therapy for breast cancer could be traced back to the excision of the metastatic breast cancer by oophorectomy in a premenopausal women performed by Beatson in 1896. After the development of more than 100 years, endocrine therapy plays an important role in adjuvant therapy, the rescuing treatment of its recurrence due to metastasis, and the new adjuvant endocrine therapy for breast cancer. Through analyzing the changes in the 4 aspects of endocrine treatment of breast cancer, i.e., the original simple excision of the endocrine organs, tamoxifen, drug-induced ovarian castration and the 3th generation aromatase inhibitor, the characteristics of different ages of endocrine therapy can be summarized, which would provide the reference for the new developmental trend of this therapy. PMID- 26268257 TI - [Identification and re-collection of Bianque's medical works]. AB - Whenever "Biarique's medical works" is mentioned, it means the work collection of an individual school. Through the identification and rearrangement of the fragments of Bianque's medical works from the extant literature, the three clues of the extant works have been sorted out, including Huangdi Bianque Mai Shu (Yellow Emperor and Bianque's Pulse Books) inherited by Canggong. It recreates the outline of the lost Bianque' medical works, and even displays the details of such outline to a certain extent. The main content of Bian que mai shu (Bianque's Pulse Book) collected by Canggong had been recorded in Wang Shuhe's Mai jing (The Pulse Classic), which were inherited in different forms in the extant Nei jing (Internal Classic) and a part of the content in the late editions were collected in Nan jing (Classic of Difficult Issues). Wu se mai (five-color pulse) was inherited from Mai jing (The Pulse Classic), the "Xianggong Wen Bianque" (Xianggong Catechism on Bianque) recorded in Shan fan fang (The Refined and Extracted Prescriptions) written by Xie Shitai in the Six Dynasties, the "Huangdi Wen Bianque" (Questions and Answers between Yellow Emperor and Bianque) in Qian jin yi fang (A supplement to the Essential Prescriptions worth a Thousand Gold), as well as from Ling shu: Wu se (Miraculous Pivot: Five Colors). In this paper, the notable and hot cases in the present academic field are analyzed, aiming to arouse people's attention to the methods and insights of literature research, as well as the reconsideration on the importance of the deep and solid research on the extant literatures. PMID- 26268258 TI - [The compilation, contents and spread of Qing li Shan jiu Fang (Formulary for Effective Rescuing in the Qingli Reign]. AB - Qing li shan jiu fang (Formulary for Effective Rescuing in the Qingli Reign), compiled by Hanlin Academy of Medical Official in 1048 under the decree of the Emperor, is a medical formulary exclusively used to prevent and control poisonous parasite disease. It is composed of formulae provided by a medical scholar of Fuzhou, Lin Shiyuan, together with other formulae collected by the imperial physicians and so on. Unfortunately, it was lost about after the demise of the Southern Song Dynasty. However, in the Southern Song Dynasty, two books, Liang Kejia's Chun xi san shan zhi and Hong Mai's Yi jian zhi bu, do record the progress of its compilation, parts of its contents and the condition of its spread and application. Moreover, they also describe the kinds, the feature, the epidemic, prevention and cure of parasite poison. It is especially good that this book preserves three famous formulae, including Zhi gu du zheng fang (Orthodox Formula for Treating Parasitic Poisons) (called A Cathartic Formula with 8 Ingredients in the Yuan Dynasty), Jie du wan (Antidote Pills) and He qi tang san (Powder of Decoction for Harmonious Qi), which are of medical significance for the understanding of the property of Qing li shan jiu fang. The Song emperors, the central government and local officials all paid high attention to the spread and application of this book. They not only enacted it to the counties, and provinces, but also carved it on stone steles for popularizing the knowledge of preventing parasitic poisons to medical workers and common people. PMID- 26268259 TI - [Textual research on the engraved editions of Nei wai yan fang mi chuan (Secret Teaching of Proved Prescriptions for Internal and External Diseases)]. AB - Zhao Lian's book Nei wai yan fang mi chuan (Secret Teaching of Proved Prescriptions for Internal and External Diseases) was firstly engraved in the 21st year of Guangxu reign of the Qing dynasty. There are altogether four different engraved editions separately collected in the Library of Academy of Medical Sciences, Library of Zhenjiang City, Library of Changchun University of TCM, and Library of Shanghai University of TCM, printed in different times with different sizes of its contents. It is better to call all these editions the engraved versions of Guangxu reign. All of them are engraved and printed after the mother edition with some blocks hollowed-out and supplemented. Hence, the title "engraved edition of Yiyou or the 11th year of Guangxu reign (1885) of the Qing dynasty" carried in The General Catalogue of Ancient Books of TCM is wrong. PMID- 26268260 TI - Antioxidant status in haemoglobin E carriers after acute and chronic strenuous exercises. AB - Haemoglobin E (HbE), an unstable haemoglobin, is highly susceptible to oxidative damages. We examined how acute or chronic physiological challenge induced by exercise affects antioxidant response in HbE carriers. Two independent studies were conducted in individuals with HbE trait and paired normal Hb. In study 1, sedentary participants were tested in a graded maximal exercise and blood samples were collected before, immediately after, and 45 minutes after an acute exercise. Our data showed that erythrocyte glutathione peroxidase (GPx) activity failed to recover in HbE carriers after 45 minutes of rest. In study 2, athletes were trained in a 10-week strenuous training and blood samples were collected before and after training period. We found that athletes with HbE carriers showed a larger increase in plasma GPx activity compared to those with normal Hb. These data suggest that HbE carriers could cope with exercise-induced oxidative stress by adjusting endogenous antioxidant markers. PMID- 26268261 TI - A Possible Cause of Nasolacrimal Duct Obstruction: Narrow Angle Between Inferior Turbinate and Upper Part of the Medial Wall of the Maxillary Sinus. AB - BACKGROUND: To search the relationships between the primary nasolacrimal duct obstruction and the angle between the bony inferior turbinate and upper part of the medial wall of the maxillary sinus. DESIGN: Retrospective study. PARTICIPANTS AND METHODS: Computed tomography findings of 35 patients with primary nasolacrimal duct obstruction and 100 sides of 50 individuals were reviewed. While the study group was composed of patients who had external dacryocystorhinostomy surgery, the control group was composed of patients who had CT scans due to headache, sinusitis and smell dysfunction. Epiphora complaint was evaluated with the lacrimal syringing. The exclusion criteria were: age less than 20 years, previous nose, sinus, turbinate or lacrimal surgery, prior history of maxillofacial fracture, nasopharyngeal malignancy, reflex hypersecretion, and associated pathology of the lacrimal canaliculi. MAIN OUTCOME MEASURES: The angle of inferior turbinate. RESULTS: The mean angles were 53.2 degrees (range, 37.9 82.9 degrees ) for affected side of the study group, 58.6 degrees (range, 32 85.3 degrees ) for the unaffected side of the study group and 56.8 degrees (range, 41.2-76.9 degrees ) in the control group. The difference between the angles was statistically significant between the study and the control groups (p < 0.05). The difference between the operated and non-operated sides of the study group was also statistically significant (p < 0.05). CONCLUSION: Although this study was performed in a small group, we thought that the narrow angle between the bony inferior turbinate and upper part of the medial wall of the maxillary sinus might be a possible causative factor in primary acquired nasolacrimal duct obstructions. PMID- 26268262 TI - Off Pump Coronary Artery Bypass Surgery for Multivessel Disease in Pregnancy. AB - A 31 year old female with known history of coronary artery disease and percutaneous coronary intervention presented with acute coronary syndrome. Unknown that patient was pregnant she had inadvertent radiation exposure to the fetus during cardiac catheterization which showed triple vessel disease and severe left ventricular dysfunction. Patient subsequently underwent multivessel off pump coronary artery bypass surgery with intraaortic balloon pump support after declining the recommendation for abortion. Postoperative course was uneventful and patient subsequently delivered a full term healthy baby several months later.Off pump revascularization with its ability to maintain pulsatile perfusion to the fetus should be considered if technically feasible for severe coronary artery disease requiring surgery during pregnancy. PMID- 26268263 TI - A novel strategy for evaluating tilt test in athletes with syncope. AB - BACKGROUND: The tilt test is used for the diagnosis of reflex syncope (RS) and is characterized by low sensitivity, especially in athletes. The objective of the study was the implementation of a novel diagnostic strategy for the tilt test without pharmacologic provocation in athletes based on haemodynamic criteria. METHODS: A passive tilt test for 30 min was performed in 132 athletes (53 with a history of RS, 79 without RS). Measurement of haemodynamic, heart rate variability (HRV) and baroreflex sensitivity parameters was performed. RESULTS: Tilt testing yielded 34% sensitivity and 94% specificity. Among negative tilt test responders, the ones with RS had increased heart rate (HR) (89 +/- 11 vs 81 +/- 10 bpm, p < 0.001), stroke index (SI) (40.2 +/- 7.1 vs 35.5 +/- 9.7 ml/m(2), p = 0.013), cardiac index (CI) (3.5 +/- 0.6 vs 2.8 +/- 0.8 l/(min.m(2)), p < 0.001) and decreased total peripheral resistance index (TPRI) (2230 +/- 362 vs 2965 +/- 725 dyne.s m(2)/cm(5), p < 0.001), low frequency component of HRV (76.2% (49.0-88.4) vs 79.7% (10.2-91.1), p = 0.045) during head-up tilt, compared with those without RS. Receiver-operating characteristic (ROC) curve analysis showed that among athletes with a negative tilt test the area under the curve (AUC) values were 0.727 (0.626-0.828) for HR (p < 0.001), 0.707 (0.611-0.804) for SI (p = 0.001), 0.847 (0.774-0.920) for CI (p < 0.001), 0.830 (0.754-0.905) for TPRI (p < 0.001). Further stratification of negative tilt test responders, characterizing their results as positive when TPRI <2800 dyne.s m(2)/cm(5) and CI >3 l/(min.m(2)), resulted in 85% sensitivity and 76% specificity. CONCLUSION: Our results provide supportive evidence that a novel stratification based on haemodynamic criteria can improve the sensitivity of the tilt test for the diagnosis of RS in athletes. PMID- 26268264 TI - The future of low-density lipoprotein cholesterol lowering therapy: An end to statin exceptionalism? PMID- 26268266 TI - Implementation of health risk assessments with family health history: barriers and benefits. AB - Health risk assessments provide an opportunity to emphasise health promotion and disease prevention for individuals and populations at large. A key component of health risk assessments is the detailed collection of family health history information. This information is helpful in determining risk both for common chronic conditions and more rare diseases as well. While the concept of health risk assessments has been around since the Framingham Heart Study was launched in the 1950s, and such assessments are commonly performed in the workplace today, the US healthcare system has been slow to embrace them and the emphasis on prevention that they represent. Before wider implementation of health risk assessments within healthcare can be seen, several concerns must be addressed: (1) provider impact, (2) patient impact, (3) validity of patient-entered data and (4) health outcomes effect. Here, we describe recent developments in health risk assessment design that are helping to address these issues. PMID- 26268265 TI - Workplace training for senior trainees: a systematic review and narrative synthesis of current approaches to promote patient safety. AB - BACKGROUND: Preventable harm is one of the top six health problems in the developed world. Developing patient safety skills and knowledge among advanced trainee doctors is critical. Clinical supervision is the main form of training for advanced trainees. The use of supervision to develop patient safety competence has not been established. OBJECTIVE: To establish the use of clinical supervision and other workplace training to develop non-technical patient safety competency in advanced trainee doctors. DATA SOURCES: Keywords, synonyms and subject headings were used to search eight electronic databases in addition to hand-searching of relevant journals up to 1 March 2014. METHOD: Titles and abstracts of retrieved publications were screened by two reviewers and checked by a third. Full-text articles were screened against the eligibility criteria. Data on design, methods and key findings were extracted. Clinical supervision documents were assessed against components common to established patient safety frameworks. Findings from the reviewed articles and document analysis were collated in a narrative synthesis. RESULTS: Clinical supervision is not identified as an avenue for embedding patient safety skills in the workplace and is consequently not evaluated as a method to teach trainees these skills. Workplace training in non-technical patient safety skills is limited, but one-off training courses are sometimes used. CONCLUSIONS: Clinical supervision is the primary avenue for learning in postgraduate medical education but the most overlooked in the context of patient safety learning. The widespread implementation of short courses is not matched by evidence of rigorous evaluation. Supporting supervisors to identify teaching moments during supervision and to give weight to non-technical skills and technical skills equally is critical. PMID- 26268267 TI - Taking TASC to TASK: Evolving from nomenclature to guidelines. PMID- 26268268 TI - An Update on Methods for Revascularization and Expansion of the TASC Lesion Classification to Include Below-the-Knee Arteries: A Supplement to the Inter Society Consensus for the Management of Peripheral Arterial Disease (TASC II). AB - The Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC) guidelines were last updated in 2007 (TASC II) and represented the collaboration of international vascular specialties involved in the management of patients with peripheral arterial disease (PAD). Since the publication of TASC II, there have been innovations in endovascular revascularization strategies for patients with PAD. The intent of this publication is to provide a complete anatomic lower limb TASC lesion classification, including the infrapopliteal segment, and an updated literature review of new endovascular techniques and practice patterns employed by vascular specialists today. PMID- 26268269 TI - The NF-kappaB essential modulator (NEMO) controls podocyte cytoskeletal dynamics independently of NF-kappaB. AB - Maintenance of the glomerular filtration barrier with its fenestrated endothelium, the glomerular basement membrane, and the podocytes as the outer layer, is a major prerequisite for proper renal function. Tight regulation of the balance between plasticity and rigidity of the podocytes' architecture is required to prevent the onset of glomerular disease, mainly proteinuria. The underlying cellular signaling pathways that regulate the organization of the podocytes' cytoskeleton are still a matter of controversial debate. In this study, we investigated the role of the NF-kappaB signaling pathway in podocyte cytoskeletal dynamics. As previously published, genetic inhibition of the NF kappaB essential modulator (NEMO) in podocytes does not affect glomerular function under physiological, nonstressed conditions nor does it alter the initial podocyte response in an experimental glomerulonephritis (NTN) model (Brahler S, Ising C, Hagmann H, Rasmus M, Hoehne M, Kurschat C, Kisner T, Goebel H, Shankland SJ, Addicks K, Thaiss F, Schermer B, Pasparakis M, Benzing T, Brinkkoetter PT. Am J Physiol Renal Physiol 303: F1473-F1475, 2012). Quite the contrary, podocyte-specific NEMO null mice recovered significantly faster and did not develop glomerulosclerosis and end-stage renal failure over time. Here, we show that cytoskeletal rearrangements and increased podocyte motility following stimulation with IL-1, TNF-alpha, or LPS depend on NEMO. NEMO also regulates the phosphorylation of the MAP kinase ERK1/2 and suppresses the activation of RhoA following stimulation with IL-1. The migratory response and altered ERK1/2 phosphorylation is independent of NF-kappaB signaling as demonstrated by expression of a mutant IkappaB resistant to phosphorylation and degradation. In conclusion, signaling through NEMO might not only be involved in the production of NF-kappaB proinflammatory chemokines but also regulates podocyte dynamics independently of NF-kappaB, most likely through small GTPases and MAP kinases. PMID- 26268271 TI - The Impact of Intimate Partner Violence on Women's Physical Health: Findings From the Missouri Behavioral Risk Factor Surveillance System. AB - Intimate partner violence (IPV) is a significant public health problem. It has far reaching consequences such as social and economic costs, as well as a negative impact on women's health outcomes. This study assessed the relationship between IPV and health risk factors, health behaviors, and poor mental health in Missouri women utilizing 2005 Missouri Behavioral Risk Factor Surveillance System (BRFSS) data ( n = 3,110). Moderators (demographic indicators) of the relationship between IPV and health risk factors (high blood pressure, high cholesterol, and obesity) and health behaviors (physical inactivity, smoking, and binge drinking) were also examined. Women with a history of IPV were more likely to engage in health-compromising behaviors such as smoking and binge drinking, be obese, and report more poor mental health days compared with women without a history of IPV. Demographic variables moderated the relationship between IPV, obesity, smoking, high blood pressure, and high cholesterol. These findings underscore the importance that clinics, community, or other health care settings can play in identifying women who are victims of or have a history of IPV and provide them with appropriate resources as well as targeted interventions to reduce morbidity in this population. PMID- 26268272 TI - Pacific Peoples, Violence, and the Power and Control Wheel. AB - This qualitative project was the first to study values and practices about sexual assault among migrant communities from the Cook Islands, Fiji, Niue, Samoa, Tokelau, Tonga, and Tuvalu in New Zealand. It aimed to identify customs, beliefs, and practices among these ethnic groups that were protective and preventive factors against sexual violence. Researchers were ethnically matched with 78 participants from the seven ethnic communities, and conducted individual interviews and one female focus group using protocols that were culturally appropriate for each ethnic group. Interviews were thematically analyzed. The study identified the brother-sister covenant and the sanctity of women as strong protective and preventive factors against sexual violence, expressed differently in each culture. Most participants viewed sexual violence as involving their extended families, village, and church communities, rather than solely the individuals concerned. However, the communal values and practices of these seven Pacific cultures raise questions about the individualistic assumptions and the meaning of violence underlying the Power and Control Wheel and the Duluth Model of domestic violence. It also raises questions about how such an individualized model can help services effectively support women in these collective societies who are experiencing violence, and how it can contribute to Pacific community prevention of violence. This study is therefore relevant to countries with significant populations of Pacific peoples and other collective cultures. PMID- 26268270 TI - PKC-alpha-dependent augmentation of cAMP and CREB phosphorylation mediates the angiotensin II stimulation of renin in the collecting duct. AB - In contrast to the negative feedback of angiotensin II (ANG II) on juxtaglomerular renin, ANG II stimulates renin in the principal cells of the collecting duct (CD) in rats and mice via ANG II type 1 (AT1R) receptor, independently of blood pressure. In vitro data indicate that CD renin is augmented by AT1R activation through protein kinase C (PKC), but the exact mechanisms are unknown. We hypothesize that ANG II stimulates CD renin synthesis through AT1R via PKC and the subsequent activation of cAMP/PKA/CREB pathway. In M 1 cells, ANG II increased cAMP, renin mRNA (3.5-fold), prorenin, and renin proteins, as well as renin activity in culture media (2-fold). These effects were prevented by PKC inhibition with calphostin C, PKC-alpha dominant negative, and by PKA inhibition. Forskolin-induced increases in cAMP and renin expression were prevented by calphostin C. PKC inhibition and Ca2+ depletion impaired ANG II mediated CREB phosphorylation and upregulation of renin. Adenylate cyclase 6 (AC) siRNA remarkably attenuated the ANG II-dependent upregulation of renin mRNA. Physiological activation of AC with vasopressin increased renin expression in M-1 cells. The results suggest that the ANG II-dependent upregulation of renin in the CD depends on PKC-alpha, which allows the augmentation of cAMP production and activation of PKA/CREB pathway via AC6. This study defines the intracellular signaling pathway involved in the ANG II-mediated stimulation of renin in the CD. This is a novel mechanism responsible for the regulation of local renin angiotensin system in the distal nephron. PMID- 26268273 TI - The Relationship Between Sexual History, Bullying Victimization, and Poor Mental Health Outcomes Among Heterosexual and Sexual Minority High School Students: A Feminist Perspective. AB - This study uses a feminist theoretical framework to extend the literature on the relationship between sexual history, bullying victimization, and poor mental health outcomes. First, we examined whether an association between the sexual double standard and bullying victimization would apply to sexual minority youth the same way it applies to heterosexual youth. A second aim was to assess whether sexual minority boys, typically stereotyped as effeminate, would report the highest odds of bullying victimization. A third and final aim of our study was to look at the joint effect of sex and sexual intercourse on depression and suicidal ideation. Our analytic sample ( N = 9,300) was from the 2009, 2011, and 2013 Rhode Island Youth Risk Behavior Surveys. Findings demonstrated that heterosexual girls who engaged in sexual intercourse had significantly higher adjusted odds of bullying victimization than heterosexual boys who engaged in the same behavior. Similar results were not found for sexual minority adolescents, suggesting the sexual double standard may not apply to sexual minority adolescents in the same way it applies to heterosexual adolescents. Consistent with our second hypothesis, sexual minority boys reported the highest odds of being recently bullied compared with heterosexual boys. Among students who were recently bullied, sexual minority girls displayed the highest adjusted odds of recent depression and suicidal ideation. Our study demonstrated that using a feminist theoretical framework broadens our understanding of why girls and sexual minority boys are particularly vulnerable to bullying victimization and the sequel of depression and suicidal ideation. PMID- 26268275 TI - It is not appropriate to dismiss inappropriate care. PMID- 26268276 TI - Not so innocent bystanders. PMID- 26268277 TI - Sight-saving science: specialist eye care using satellite technology. PMID- 26268278 TI - Sexual equality, discrimination and harassment in medicine: it's time to act. PMID- 26268279 TI - Sexual abuse of doctors by doctors: professionalism, complexity and the potential for healing. PMID- 26268280 TI - Ethical challenges for doctors working in immigration detention. PMID- 26268281 TI - Screening tests for gonorrhoea should first do no harm. PMID- 26268282 TI - Screening tests for gonorrhoea should first do no harm. PMID- 26268283 TI - Screening tests for gonorrhoea should first do no harm. PMID- 26268284 TI - Discrimination, bullying and sexual harassment: where next for medical leadership? PMID- 26268285 TI - The Royal Australasian College of Physicians position statement on refugee and asylum seeker health. PMID- 26268286 TI - In search of professional consensus in defining and reducing low-value care. AB - Care that confers no benefit or benefit that is disproportionately low compared with its cost is of low value and potentially wastes limited resources. It has been claimed that low-value care consumes at least 20% of health care resources in the United States - the comparable figure in Australia is unknown but there is emerging evidence of overuse of diagnostic tests and therapeutic procedures. Very few clinical interventions are of no value in every clinical circumstance, and efforts to label interventions as being so will meet with professional resistance. In the context of complex and highly individualised clinical decisions, nuanced clinical judgements of experienced and well informed clinicians are likely to outperform any service-level measurement and incentive program aimed at recognising and reducing low-value care. Public policy interventions should focus on supporting clinician-led efforts to seek professional consensus on what constitutes low-value care and the best means for reducing it. PMID- 26268287 TI - Identifying and acting on potentially inappropriate care. AB - OBJECTIVE: To develop a model to measure potentially inappropriate care in Australian hospitals. DESIGN: Secondary analysis of computerised hospital discharge data for all Australian hospitals for the 2010-11 financial year. MAIN OUTCOME MEASURE: Hospital-specific incidence of selected diagnosis-procedure pairs identified as inappropriate in other literature. RESULTS: Five hospital procedures that are not supported by clinical evidence happened more than 100 times a week, on average. The most frequent of these do-not-do treatments was hyperbaric oxygen therapy for a range of specific conditions (4659 admissions in 2010-11). The rate of do-not-do procedures varied greatly, even among comparator hospitals that provided the procedure and that treated the relevant patient group. Among comparator hospitals, an average of 3.3% of patients with osteoarthritis of the knee received arthroscopic lavage and debridement of the knee (a do-not-do treatment), but four hospitals had rates of over 20%. There was also great variation in hospital-specific rates of procedures that should not be done routinely. CONCLUSION: Hospital-specific rates of do-not-do treatments vary greatly. Hospitals should be informed about their relative performance. Hospitals that have sustained, high rates of do-not-do treatments should be subject to external clinical review by expert peers. PMID- 26268288 TI - Tracking funded health intervention research. AB - OBJECTIVE: To describe the research publication outputs from intervention research funded by Australia's National Health and Medical Research Council (NHMRC). DESIGN AND SETTING: Analysis of descriptive data and data on publication outputs collected between 23 July 2012 and 10 December 2013 relating to health intervention research project grants funded between 1 January 2003 and 31 December 2007. MAIN OUTCOME MEASURES: Stages of development of intervention studies (efficacy, effectiveness, replication, adaptation or dissemination of intervention); types of interventions studied; publication output per NHMRC grant; and whether interventions produced statistically significant changes in primary outcome variables. RESULTS: Most of the identified studies tested intervention efficacy or effectiveness in clinical or community settings, with few testing the later stages of intervention development, such as replication, adaptation or dissemination. Studies focused largely on chronic disease treatment and management, and encompassed various medical and allied health disciplines. Equal numbers of studies had interventions that produced statistically significant results on primary outcomes, (27) and those that did not (27). The mean number of total published articles per grant was 3.3, with 2.0 articles per grant focusing on results, and the remainder covering descriptive, exploratory or methodological aspects of intervention research. CONCLUSIONS: Our study provides a benchmark for the publication outputs of NHMRC-funded health intervention research in Australia. Research productivity is particularly important for intervention research, where findings are likely to have more immediate and direct applicability to health policy and practice. Tracking research outputs in this way provides information on whether current research investment patterns match the need for evidence about health care interventions. PMID- 26268289 TI - "Teaching by humiliation" and mistreatment of medical students in clinical rotations: a pilot study. AB - OBJECTIVE: To generate a contemporary understanding of "teaching by humiliation" as experienced by medical students in Australia. DESIGN, SETTING AND PARTICIPANTS: In this pilot study, we surveyed final-stage medical students from two Australian medical schools about their experiences of teaching by humiliation during their adult and paediatric clinical rotations. The students were invited to complete the anonymous survey at the end of their paediatric rotation in Semester 2 of 2013. We used descriptive statistics to analyse quantitative data, and a grounded theory approach to analyse qualitative data. MAIN OUTCOME MEASURES: Student reports of experiencing or witnessing teaching by humiliation during their adult and paediatric clinical rotations. RESULTS: Of 151 students invited to participate, 146 (96.7%) completed the survey. Most students reported experiencing (108; 74.0%) or witnessing (118; 83.1%) teaching by humiliation during adult clinical rotations. Smaller but still sizeable proportions had experienced (42; 28.8%) or witnessed (64; 45.1%) it during their paediatric clinical rotation. The humiliating and intimidating behaviours students experienced were mostly more subtle than overt and included aggressive and abusive questioning techniques. The students' responses to these practices ranged from disgust and regret about entering the medical profession to endorsement of teachers' public exposure of a student's poor knowledge. CONCLUSIONS: Practices associated with humiliating medical students persist in contemporary medical education. These practices need to be eradicated, given the evidence that they affect students' learning and mental health and are dissonant with formal professionalism curricula. Interventions are needed to interrupt the transgenerational legacy and culture in which teaching by humiliation is perpetuated. PMID- 26268290 TI - Fascioliasis in Australian travellers to Bali. PMID- 26268291 TI - Sexual harassment in the medical profession: legal and ethical responsibilities. AB - Sexual harassment of women in medicine has become a subject of national debate after a senior female surgeon stated that if a woman complained of unwanted advances her career would be jeopardised, and subsequent reports suggest that sexual harassment is a serious problem in the medical profession. Sexual harassment of women in the medical profession by their colleagues presents substantial legal, ethical and cultural questions for the profession. Women have enforceable legal rights to gender equality and freedom from sexual harassment in the workplace. Both individual offenders and employers face significant legal consequences for sexual harassment in every Australian state and territory, and individual medical practitioners and employers need to understand their legal and ethical rights and responsibilities in this context. An individual offender may be personally liable for criminal offences, and for breaching anti-discrimination legislation, duties owed in civil law, professional standards and codes of conduct. An employer may be liable for breaching anti-discrimination legislation, workplace safety laws, duties owed in contract law, and a duty of care owed to the employee. Employers, professional colleges and associations, and regulators should use this national debate as an opportunity to improve gender equality and professional culture in medicine; individuals and employers have clear legal and ethical obligations to minimise sexual harassment to the greatest extent possible. PMID- 26268292 TI - Bullying and harassment: can we solve the problem? PMID- 26268293 TI - Ethical considerations in the management of Ebola virus disease. AB - Is it ethically appropriate in some circumstances for HCWs to decline to care for patients with EVD? How should treatment decisions be made regarding limitation of therapy for patients with EVD? There are two main ethical questions regarding the critical care of patients with EVD in an Australian setting: Is it ethically appropriate in some circumstances for HCWs to decline to care for patients with EVD? How should treatment decisions be made regarding limitation of therapy for patients with EVD? The key concern is ensuring that no patient is denied therapy that should be provided, while preventing unnecessary risk to HCWs. It is imperative to develop an approach that facilitates rigorous, evidence-based and ethically justifiable decision making, which should include a predetermined, institutionally endorsed process for assessing difficult clinical scenarios as they arise. PMID- 26268295 TI - Negotiating the complex maze of claims of dietary cures for cancer. PMID- 26268296 TI - Impact of grief delivered via media technology. PMID- 26268297 TI - Perspectives from the field: Ebola response in Sierra Leone. PMID- 26268298 TI - Facile Fabrication of Lubricant-Infused Wrinkling Surface for Preventing Thrombus Formation and Infection. AB - Despite the advanced modern biotechniques, thrombosis and bacterial infection of biomedical devices remain common complications that are associated with morbidity and mortality. Most antifouling surfaces are in solid form and cannot simultaneously fulfill the requirements for antithrombosis and antibacterial efficacy. In this work, we present a facile strategy to fabricate a slippery surface. This surface is created by combining photografting polymerization with osmotically driven wrinkling that can generate a coarse morphology, and followed by infusing with fluorocarbon liquid. The lubricant-infused wrinkling slippery surface can greatly prevent protein attachment, reduce platelet adhesion, and suppress thrombus formation in vitro. Furthermore, E. coli and S. aureus attachment on the slippery surfaces is reduced by ~98.8% and ~96.9% after 24 h incubation, relative to poly(styrene-b-isobutylene-b-styrene) (SIBS) references. This slippery surface is biocompatible and has no toxicity to L929 cells. This surface-coating strategy that effectively reduces thrombosis and the incidence of infection will greatly decrease healthcare costs. PMID- 26268299 TI - The fate of calf perforator veins after saphenous vein laser ablation. AB - PURPOSE: We aimed to assess hemodynamic changes in calf perforator veins (PVs) after endovenous laser ablation (EVLA) of saphenous veins. METHODS: The series comprised 60 limbs of 41 patients (27 female, 14 male; median age, 43 years [range, 22-78 years]) who underwent EVLA for varicose veins. All patients were prospectively evaluated by means of color Doppler ultrasonography before and after the procedure. RESULTS: EVLA did not change the rate of incompetent PVs (preoperatively, 154/483 [32%] vs. postoperatively, 167/501 [33%]; P = 0.173), but significantly increased the total number of all PVs (n=483 vs. n=501, P = 0.036). Following EVLA, 28% of the limbs had thrombosis of PVs, 34% had new US detectable PVs, 42% showed new competency, and 52% showed new incompetency. New competent PVs were found more commonly in the medial leg (ablation site) than the lateral leg (nonablation site) (28.3% vs. 11.7%, P = 0.016), while new incompetent PVs were found more commonly in nonablation site than ablation site (31.7% vs. 18.3%, P = 0.086). Additionally, new competent PVs in the posterior leg were found more often in patients who had small saphenous vein ablation than patients who did not (30% vs. 0%, P = 0.002). CONCLUSION: EVLA induces numerous changes in calf PVs. These changes seem to result from flow offloading in ablation site and onloading in nonablation site in the early postablation period. PMID- 26268300 TI - CT-guided fine-needle localization of ground-glass nodules in re-aerated lung specimens: localization of solitary small nodules or multiple nodules within the same lobe. AB - PURPOSE: We aimed to explore the value of localizing small ground-glass nodules (GGNs; <10 mm) or multiple GGNs within the same lobe in re-aerated lung specimens using CT-guided fine-needle localization. METHODS: Thirty-five lung specimens containing single small GGNs (<10 mm) and eight specimens containing two or more GGNs in the same lobe were re-aerated with an inflatable aerator. All lesions were localized via CT-guided fine-needle localization following re-aeration. The specimens were then sent for pathologic sampling and qualitative diagnosis. RESULTS: All 69 nodules from 43 cases were successfully localized using CT-guided fine-needle localization following re-aeration. CONCLUSIONS: CT-guided fine needle localization of lesions in surgical specimens under constant, moderate mechanical aeration allows for the rapid and accurate localization of lesions and helps avoid damage from preoperative localization. PMID- 26268301 TI - Comparative study of the corrosion behavior of peripheral stents in an accelerated corrosion model: experimental in vitro study of 28 metallic vascular endoprostheses. AB - PURPOSE: Clinical cases of stent-fractures show that corrosion behavior might play a role in these fractures. Implanted in vivo, especially in combination with other implanted foreign materials, these metallic products are exposed to special conditions, which can cause a process of corrosion. Here, we aimed to test the corrosion potential of stents made of different materials in an in vitro setting. METHODS: A total of 28 peripheral stents of different materials (nitinol, cobalt chromium-nickel, tantalum, V4A) and surface treatments (electropolish, mechanical polish, no polish) were tested in vitro. Corrosion was accelerated by applying a constant voltage of 3.5 V and amperage of 1.16 mA in 0.9% NaCl. RESULTS: Nitinol stents showed the lowest susceptibility to corrosion and the longest period without damage. The Memotherm II(r) (BARD Angiomed(r)) was the only stent that showed neither macroscopic nor microscopic damages. The worst performing material was cobalt-chromium-nickel, which showed corrosion damages about ten times earlier compared to nitinol. Considering the reasons for termination of the test, nitinol stents primarily showed length deficits, while V4A and tantalum stents showed fractures. Cobalt-chromium-nickel stents had multiple fractures or a complete lysis in equal proportions. When placed in direct contact, nitinol stents showed best corrosion resistance, regardless of what material they were combined with. In terms of polishing treatments, electropolished stents performed the best, mechanical-polished stents and those without polishing treatment followed. CONCLUSION: The analysis of corrosion behavior may be useful to select the right stent fulfilling the individual needs of the patient within a large number of different stents. PMID- 26268302 TI - Angiographic analysis of the lateral intercostal artery perforator of the posterior intercostal artery: anatomic variation and clinical significance. AB - PURPOSE: Knowledge of the anatomic variations of the posterior intercostal artery (PICA) and its major branches is important during transthoracic procedures and surgery. We aimed to identify the anatomic features and variations of the lateral intercostal artery perforator (LICAP) of the PICA with selective PICA arteriography. METHODS: We retrospectively evaluated 353 PICAs in 75 patients with selective PICA arteriography for the following characteristics: incidence, length (as number of traversed intercostal spaces), distribution at the hemithorax (medial half vs. lateral half), and size as compared to the collateral intercostal artery of the PICA. RESULTS: The incidence of LICAPs was 35.9% (127/353). LICAPs were most commonly observed in the right 8th-11th intercostal spaces (33%, 42/127) and in the medial half of the hemithorax (85%, 108/127). Most LICAPs were as long as two (35.4%, 45/127) or three intercostal spaces (60.6%, 77/127). Compared to the collateral intercostal artery, 42.5% of LICAPs were larger (54/127), with most of these observed in the right 4th-7th intercostal spaces (48.8%, 22/54). CONCLUSION: We propose the clinical significance of the LICAP as a potential risk factor for iatrogenic injury during posterior transthoracic intervention and thoracic surgery. For example, skin incisions must be as superficial as possible and directed vertically at the right 4th-7th intercostal spaces and the medial half of the thorax. Awareness of the anatomical variations of the LICAPs of the PICA will allow surgeons and interventional radiologists to avoid iatrogenic arterial injuries during posterior transthoracic procedures and surgery. PMID- 26268303 TI - Computed tomography arterial portography for assessment of portal vein injury after blunt hepatic trauma. AB - PURPOSE: Intrahepatic portal vein injuries secondary to blunt abdominal trauma are difficult to diagnose and can result in insidious bleeding. We aimed to compare computed tomography arterial portography (CTAP), reperfusion CTAP (rCTAP), and conventional computed tomography (CT) for diagnosing portal vein injuries after blunt hepatic trauma. METHODS: Patients with blunt hepatic trauma, who were eligible for nonoperative management, underwent CTAP, rCTAP, and CT. The number and size of perfusion defects observed using the three methods were compared. RESULTS: A total of 13 patients (seven males/six females) with a mean age of 34.5+/-14.1 years were included in the study. A total of 36 hepatic segments had perfusion defects on rCTAP and CT, while there were 47 hepatic segments with perfusion defects on CTAP. The size of perfusion defects on CT (239 cm3; interquartile range [IQR]: 129.5, 309.5) and rCTAP (238 cm3; IQR: 129.5, 310.5) were significantly smaller compared with CTAP (291 cm3; IQR: 136, 371) (both, P = 0.002). CONCLUSION: Perfusion defects measured by CTAP were significantly greater than those determined by either rCTAP or CT in cases of blunt hepatic trauma. This finding suggests that CTAP is superior to rCTAP and CT in evaluating portal vein injuries after blunt liver trauma. PMID- 26268305 TI - Validation of a gene expression profile predictive of the risk of radiation induced fibrosis in women treated with breast conserving therapy. PMID- 26268304 TI - Addictive behaviors and personality traits in adolescents. AB - INTRODUCTION: Behavioral addictions refer to repeated dysfunctional behaviors that do not involve the ingestion of addictive substances. Studies on the association between behavioral addictions and personality traits have noted in individuals with problematic behaviors a high proclivity toward impulsivity and sensation-seeking and a low predisposition to harm avoidance. The majority of these studies have focused on adults, while far fewer have involved adolescents. METHODS: The study population was 109 high school students (age range 15-18 years) in Turin, Italy. Participants completed an assessment that comprised a demographic questionnaire and 3 self-report questionnaires: the Shorter PROMIS Questionnaire (SPQ), the Internet Addiction Test (IAT), and the Multidimensional Questionnaire for Adolescents (QMA). RESULTS: A gender-related difference in the risk of developing an addictive behavior was observed, with a significantly higher percentage of risk seen for several addiction tendencies among the males. Statistically significant correlations emerged between some personality determinants and certain addictive behaviors. DISCUSSION: The study pinpoints epidemiological indicators for the extent of this growing problem among adolescents. CONCLUSIONS: The findings have implications for identifying protection factors and risk factors for addictive behaviors and related psychiatric disorders, and the development of primary prevention strategies derived from such factors. PMID- 26268306 TI - Hospitalized pain patients have recently doubled: a retrospective case series study in Shenzhen Nanshan People's Hospital of China. AB - AIM: To study the characteristics of hospitalized pain patients in Shenzhen with the aim of identifying some of the social, economic and therapeutic aspects of pain management in China. METHODS: A retrospective study was designed to collect the information of 3061 hospitalized pain patients in 2003, 2007 and 2011. Their demographic characteristics, diagnoses of pain types, hospitalization, therapeutic effect, economic cost and payment types were analyzed. RESULTS: The number of female patients significantly increased with time. The patient's average age increased from 41.3 in 2003 to 49.7 years old in 2011. The most common diagnosis of pain was lumbar intervertebral disc herniation. The total hospitalization days of each patient per year significantly decreased from 15.7 days in 2003 to 10.4 days in 2011. However, the hospitalization cost for each patient was almost doubled. CONCLUSION: The hospitalized pain patients and their economic burdens have almost been doubled in the recent four years. PMID- 26268307 TI - Magnetotactic bacteria: nanodrivers of the future. AB - Magnetotactic bacteria (MTB) represent a heterogeneous group of Gram-negative aquatic prokaryotes with a broad range of morphological types, including vibrioid, coccoid, rod and spirillum. MTBs possess the virtuosity to passively align and actively swim along the magnetic field. Magnetosomes are the trademark nano-ranged intracellular structures of MTB, which comprise magnetic iron-bearing inorganic crystals enveloped by an organic membrane, and are dedicated organelles for their magnetotactic lifestyle. Magnetosomes endue high and even dispersion in aqueous solutions compared with artificial magnetites, claiming them as paragon nanomaterials. MTB and magnetosomes offer high technological potential in modern science, technology and medicines. This review focuses on the applicability of MTB and magnetosomes in various areas of modern benefits. PMID- 26268308 TI - Economic resources consumption structure in severe hypoglycemia episodes: a systematic review and meta-analysis. AB - Diabetes mellitus (DM) is associated with severe hypoglycemia events (SHEs) that vary in severity and resource consumption. Here we perform a systematic review in Medline of studies evaluating SHE-related health resource use. Eligible studies investigated patients with DM and included >=10 SHEs. We also assessed studies identified in another systematic review, and through references from the included studies. We identified 14 relevant studies and used data from 11 (encompassing 6075 patients). Study results were interpreted to fit our definitions, which sometimes required assumptions. SHE type structure was synthesized using Bayesian modeling. Estimating Type 1 & 2 DM separately revealed only small differences; therefore, we used joint results. Of the analyzed SHEs, 9.97% were hospital treated, 22.3% medical professional-treated, and 67.73% family-treated. These meta-analysis results help in understanding the structure of resource consumption following SHE and can be used in economic studies. PMID- 26268311 TI - Precision medicine: Beyond the inflection point. AB - A confluence of biological, physical, engineering, computer, and health sciences is setting the stage for a transformative leap toward data-driven, mechanism based health and health care for each individual. PMID- 26268309 TI - Atrial fibrillation in the Indigenous populations of Australia, Canada, New Zealand, and the United States: a systematic scoping review. AB - BACKGROUND: The epidemiology of atrial fibrillation (AF) among Indigenous minorities in affluent countries is poorly delineated, despite the high cardiovascular disease burden in these populations. We undertook a systematic scoping review examining the epidemiology of AF in the Indigenous populations of Australia, Canada, New Zealand (NZ) and the United States (US). METHODS: PubMed, Scopus, EMBASE and CINAHL-Plus databases were systematically searched in May 2014. Supplementary full-text searches of Google Scholar and government website searches were also undertaken. RESULTS: Key findings from 27 publications with diverse aims and methods were included. Small studies from Canada and NZ suggest higher AF prevalence in Indigenous than other populations. However, this was not reflected in a large sample of US male military veterans. No data were identified on community-based incidence rates of AF in Indigenous populations. Australian and Canadian studies indicate higher first-ever and overall AF hospitalisation rates among Indigenous than other populations, at younger ages and with more comorbidity. Studies in stroke, heart failure and other clinical groups demonstrate AF as a common comorbidity, with AF possibly more prevalent at younger ages in Indigenous people. Indigenous patients have similar early post hospitalisation adjusted mortality but higher 1-year risk-adjusted mortality than non-Indigenous patients. CONCLUSIONS: No clear epidemiological pattern of AF frequency across the considered Indigenous populations emerges from the limited available evidence. AF should be included in key conditions reported in national surveillance reports, although Indigenous identifiers are required in administrative data from Canada and the US. Sufficiently powered, community-based studies of AF epidemiology in diverse Indigenous populations are needed. PMID- 26268310 TI - EZH2 is increased in paediatric T-cell acute lymphoblastic leukemia and is a suitable molecular target in combination treatment approaches. AB - BACKGROUND: T-cell Acute Lymphoblastic Leukemia (ALL) represents about 10-15 % of pediatric ALL cases. EZH2, one of the components of Polycomb group proteins (PRC2) complex, catalyzes the trimethylation of histone H3 lysine 27 that is associated with transcriptional repression and tumor development. METHODS: We examined the expression levels of PRC2 complex in primary samples of T cells ALL at diagnosis by western blotting and real time PCR. We evaluated the effect of 3 deazaneplanocin-A (DZNep), an EZH2 inhibitor, alone and in combination with Daunoblastine on cell viability, apoptotic death and cell cycle distribution of T cell established Jurkat cell line. RESULTS: EZH2 was expressed in 75 % samples at different extents mainly with high expression level. SUZ12 was expressed in 60 % samples and EED in all samples, respectively. The Kaplan-Meier analysis shows that T-ALL expressing EZH2 had a lower probability of disease-free survival (DFS) compared to T-ALL negative for EZH2 (23 % vs 100 %) (p = 0.01). The EZH2 inhibitor DZNep used in combination with Daunoblastine was synergistic in inducing growth inhibition and increasing the apoptosis in T-ALL Jurkat cells at 48 and 72 h paralleled by EZH2 decreased expression. Moreover, the combination decreased the activity of Erk-1/2 proliferation enzymes with no effects on Akt survival pathway. CONCLUSIONS: The evaluation of EZH2 expression in pediatric T ALL can be useful in predict the clinical outcome of the patients and EZH2 can be a useful target to improve the efficacy of conventional chemotherapy in this subset of patients with bad prognosis. PMID- 26268312 TI - Exposure to SIV in utero results in reduced viral loads and altered responsiveness to postnatal challenge. AB - HIV disease progression appears to be driven by increased immune activation. Given observations that fetal exposure to infectious pathogens in utero can result in reduced immune responses, or tolerance, to those pathogens postnatally, we hypothesized that fetal exposure to HIV may render the fetus tolerant to the virus, thus reducing damage caused by immune activation during infection later in life. To test this hypothesis, fetal rhesus macaques (Macaca mulatta) were injected with the attenuated virus SIVmac1A11 in utero and challenged with pathogenic SIVmac239 1 year after birth. SIVmac1A11-injected animals had significantly reduced plasma RNA viral loads (P < 0.02) up to 35 weeks after infection. Generalized estimating equations analysis was performed to identify immunologic and clinical measurements associated with plasma RNA viral load. A positive association with plasma RNA viral load was observed with the proportion of CD8(+) T cells expressing the transcription factor, FoxP3, and the proportion of CD4(+) T cells producing the lymphoproliferative cytokine, IL-2. In contrast, an inverse relationship was found with the frequencies of circulating CD4(+) and CD8(+) T cells displaying intermediate expression of the proliferation marker, Ki 67. Animals exposed to simian immunodeficiency virus (SIV) in utero appeared to have enhanced SIV-specific immune responses, a lower proportion of CD8(+) T cells expressing the exhaustion marker PD-1, and more circulating TH17 cells than controls. Although the development of tolerance was not demonstrated, these data suggest that rhesus monkeys exposed to SIVmac1A11 in utero had distinct immune responses associated with the control of viral replication after postnatal challenge. PMID- 26268314 TI - Efficacy of a virus-vectored vaccine against human and bovine respiratory syncytial virus infections. AB - Human respiratory syncytial virus (HRSV) is a major cause of lower respiratory tract disease in children and the elderly for which there is still no effective vaccine. We have previously shown that PanAd3-RSV, which is a chimpanzee adenovirus-vectored vaccine candidate that expresses a secreted form of the HRSV F protein together with the N and M2-1 proteins of HRSV, is immunogenic in rodents and nonhuman primates, and protects mice and cotton rats from HRSV challenge. Because the extent to which protection demonstrated in rodent models will translate to humans is unclear, we have exploited the calf model of bovine RSV (BRSV) infection, which mimics HRSV disease in children more closely than do experimental models of unnatural laboratory hosts, to evaluate the safety and efficacy of the PanAd3-RSV vaccine. We show that PanAd3-RSV alone and in combination with a modified vaccinia Ankara expressing the same HRSV antigens (MVA-RSV) induced neutralizing antibodies and cellular immunity in young seronegative calves and protected against upper and lower respiratory tract infection and pulmonary disease induced by heterologous BRSV challenge. There was no evidence either of enhanced pulmonary pathology or of enhanced respiratory disease in vaccinated calves after BRSV challenge. These findings support the continued evaluation of the vectored RSV vaccines in man. PMID- 26268313 TI - Chimpanzee adenovirus- and MVA-vectored respiratory syncytial virus vaccine is safe and immunogenic in adults. AB - Respiratory syncytial virus (RSV) causes respiratory infection in annual epidemics, with infants and the elderly at particular risk of developing severe disease and death. However, despite its importance, no vaccine exists. The chimpanzee adenovirus, PanAd3-RSV, and modified vaccinia virus Ankara, MVA-RSV, are replication-defective viral vectors encoding the RSV fusion (F), nucleocapsid (N), and matrix (M2-1) proteins for the induction of humoral and cellular responses. We performed an open-label, dose escalation, phase 1 clinical trial in 42 healthy adults in which four different combinations of prime/boost vaccinations were investigated for safety and immunogenicity, including both intramuscular (IM) and intranasal (IN) administration of the adenovirus-vectored vaccine. The vaccines were safe and well tolerated, with the most common reported adverse events being mild injection site reactions. No vaccine-related serious adverse events occurred. RSV neutralizing antibody titers rose in response to IM prime with PanAd3-RSV and after IM boost for individuals primed by the IN route. Circulating anti-F immunoglobulin G (IgG) and IgA antibody-secreting cells (ASCs) were observed after the IM prime and IM boost. RSV-specific T cell responses were increased after the IM PanAd3-RSV prime and were most efficiently boosted by IM MVA-RSV. Interferon-gamma (IFN-gamma) secretion after boost was from both CD4(+) and CD8(+) T cells, without detectable T helper cell 2 (TH2) cytokines that have been previously associated with immune pathogenesis following exposure to RSV after the formalin-inactivated RSV vaccine. In conclusion, PanAd3-RSV and MVA-RSV are safe and immunogenic in healthy adults. These vaccine candidates warrant further clinical evaluation of efficacy to assess their potential to reduce the burden of RSV disease. PMID- 26268315 TI - An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease. AB - There is a clinical need for new, more effective treatments for chronic and debilitating inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. Targeting drugs selectively to the inflamed intestine may improve therapeutic outcomes and minimize systemic toxicity. We report the development of an inflammation-targeting hydrogel (IT-hydrogel) that acts as a drug delivery system to the inflamed colon. Hydrogel microfibers were generated from ascorbyl palmitate, an amphiphile that is generally recognized as safe (GRAS) by the U.S. Food and Drug Administration. IT-hydrogel microfibers loaded with the anti-inflammatory corticosteroid dexamethasone (Dex) were stable, released drug only upon enzymatic digestion, and demonstrated preferential adhesion to inflamed epithelial surfaces in vitro and in two mouse colitis models in vivo. Dex-loaded IT-hydrogel enemas, but not free Dex enemas, administered every other day to mice with colitis resulted in a significant reduction in inflammation and were associated with lower Dex peak serum concentrations and, thus, less systemic drug exposure. Ex vivo analysis of colon tissue samples from patients with ulcerative colitis demonstrated that IT-hydrogel microfibers adhered preferentially to mucosa from inflamed lesions compared with histologically normal sites. The IT-hydrogel drug delivery platform represents a promising approach for targeted enema-based therapies in patients with colonic IBD. PMID- 26268316 TI - Misdiagnosis of inclusion body myositis: two case reports and a retrospective chart review. AB - INTRODUCTION: Sporadic inclusion body myositis is the most common adult myopathy in persons aged 50 years and older. The clinical presentation includes a chronic, slowly progressive course with a predilection for weakness of the forearm flexors and quadriceps muscles. Its indolent course makes it a disease frequently missed or misdiagnosed as other neuromuscular conditions by health care professionals. The degenerative processes with amyloid accumulation distinguish sporadic inclusion body myositis from other inflammatory myopathies. Currently, no effective therapy exists. This clinical report highlights the difficulties in diagnosing the disease, examples of misdiagnosis, and inappropriate therapies that can result from misdiagnosis. CASE PRESENTATION: We present our clinical experience with 20 patients over a 10-year period and describe in depth two cases, both men, one of Indian ethnicity and the other of Hispanic ethnicity, who were referred to our neuromuscular division for second opinions and diagnosed with sporadic inclusion body myositis years after symptom onset. CONCLUSIONS: Although sporadic inclusion body myositis is rare and without effective therapy, accurate diagnosis is crucial to providing adequate counseling and information about the prognosis and disease course, and to avoiding inappropriate therapy. PMID- 26268317 TI - Anti-citrullinated protein antibodies contribute to platelet activation in rheumatoid arthritis. AB - INTRODUCTION: Although the role of platelets in rheumatoid arthritis (RA) is relatively unexplored, recent studies point towards a contribution of platelets in arthritis. We set out to determine platelet phenotype in RA and studied whether this could be influenced by the presence of anti-citrullinated protein antibodies (ACPA). METHODS: Platelets from healthy controls were incubated in the presence of plasma of patients with RA or age- and sex-matched healthy controls and plasma from ACPA(neg) or ACPA(pos) patients or in the presence of plate-bound ACPA. Characteristics of platelets isolated from patients with RA were correlated to disease activity. RESULTS: Platelets isolated from healthy controls displayed markers of platelet activation in the presence of plasma derived from RA patients, as determined by P-selectin expression, formation of aggregates and secretion of soluble CD40 ligand (sCD40L). Furthermore, levels of P-selectin expression and sCD40L release correlated with high ACPA titres. In accordance with these findings, enhanced platelet activation was observed after incubation with ACPA(pos) plasma versus ACPA(neg) plasma. Pre-incubation of platelets with blocking antibodies directed against low-affinity immunoglobulin G receptor (FcgammaRIIa) completely inhibited the ACPA-mediated activation. In addition, expression of P-selectin measured as number of platelets correlated with Disease Activity Score in 44 joints, C-reactive protein level, ACPA status and ACPA level. CONCLUSIONS: We show for the first time that ACPA can mediate an FcgammaRIIa-dependent activation of platelets. As ACPA can be detected several years before RA disease onset and activated platelets contribute to vascular permeability, these data implicate a possible role for ACPA-mediated activation of platelets in arthritis onset. PMID- 26268318 TI - Rapid growth accelerates telomere attrition in a transgenic fish. AB - BACKGROUND: Individuals rarely grow as fast as their physiologies permit despite the fitness advantages of being large. One reason may be that rapid growth is costly, resulting for example in somatic damage. The chromosomal ends, the telomeres, are particularly vulnerable to such damage, and telomere attrition thus influences the rate of ageing. Here, we used a transgenic salmon model with an artificially increased growth rate to test the hypothesis that rapid growth is traded off against the ability to maintain somatic health, assessed as telomere attrition. RESULTS: We found substantial telomere attrition in transgenic fish, while maternal half-sibs growing at a lower, wild-type rate seemed better able to maintain the length of their telomeres during the same time period. CONCLUSIONS: Our results are consistent with a trade-off between rapid growth and somatic (telomere) maintenance in growth-manipulated fish. Since telomere erosion reflects cellular ageing, our findings also support theories of ageing postulating that unrepaired somatic damage is associated with senescence. PMID- 26268319 TI - Is perception of quality more important than technical quality in patient video cases? AB - BACKGROUND: The use of video cases to demonstrate key signs and symptoms in patients (patient video cases or PVCs) is a rapidly expanding field. The aims of this study were to evaluate whether the technical quality, or judgement of quality, of a video clip influences a paediatrician's judgment on acuity of the case and assess the relationship between perception of quality and the technical quality of a selection of video clips. METHODS: Participants (12 senior consultant paediatricians attending an examination workshop) individually categorised 28 PVCs into one of 3 possible acuities and then described the quality of the image seen. The PVCs had been converted into four different technical qualities (differing bit rates ranging from excellent to low quality). RESULTS: Participants' assessment of quality and the actual industry standard of the PVC were independent (333 distinct observations, spearmans rho = 0.0410, p = 0.4564). Agreement between actual acuity and participants' judgement was generally good at higher acuities but moderate at medium/low acuities of illness (overall correlation 0.664). Perception of the quality of the clip was related to correct assignment of acuity regardless of the technical quality of the clip (number of obs = 330, z = 2.07, p = 0.038). CONCLUSIONS: It is important to benchmark PVCs prior to use in learning resources as experts may not agree on the information within, or quality of, the clip. It appears, although PVCs may be beneficial in a pedagogical context, the perception of quality of clip may be an important determinant of an expert's decision making. PMID- 26268320 TI - Detection and molecular characterisation of bovine corona and toroviruses from Croatian cattle. AB - BACKGROUND: Bovine coronavirus (BCoV) together with bovine torovirus (BToV), both members of the Coronaviridae family, order Nidovirales are the most common viral enteric pathogens. Although studied separately, their joint occurrence and the molecular diversity in cattle in Croatia have not been investigated. METHODS: A survey is carried out on 101 fecal samples from diarrheic young and adult cattle during the 3-year period from i) one large dairy herd, ii) four small herds and iii) three nasal and paired fecal samples from calves with symptoms of respiratory disease. Samples were submitted to RT-PCR and sequencing for BCoV Nucleocapsid gene, BCoV Spike gene and BToV Spike gene. RESULTS: BCoV was detected in 78.8 % of fecal samples from symptomatic cattle and three nasal and paired fecal samples from calves with respiratory symptoms. BToV was detected in 43.2 % of fecal samples from symptomatic cattle and a fecal sample from calves with respiratory symptoms. Molecular characterisation of those viruses revealed some nucleotide and aminoacid differences in relation to reference strains. CONCLUSIONS: BToV should be regarded as a relevant pathogen for cattle that plays a synergistic role in mixed enteric infections. PMID- 26268321 TI - Study on establishment and mechanics application of finite element model of bovine eye. AB - BACKGROUND: Glaucoma mainly induced by increased intraocular pressure (IOP), it was believed that the pressure that wall of eyeball withstands were determined by material properties of the tissue and stereoscopic geometry of the eyeball. In order to study the pressure changes in different parts of interior eyeball wall, it is necessary to develop a novel eye ball FEM with more accurate geometry and material properties. Use this model to study the stress changes in different parts of eyeball, especially the lamina cribrosa (LC) under normal physiological and pathological IOP, and provide a mathematical model for biomechanical studies of selected retinal ganglion cells (RGCs) death. METHODS: (1) Sclera was cut into 3.8-mm wide, 14.5-mm long strips, and cornea was cut into 9.5-mm-wide and 10-mm long strips; (2) 858 Mini BionixII biomechanical loading instrument was used to stretch sclera and cornea. The stretching rate for sclera was 0.3 mm/s, 3 mm/s, 30 mm/s, 300 mm/s; and for cornea were 0.3 mm/s and 30 mm/s. The deformation stress curve was recorded; (3) Naso-temporal and longitudinal distance of LC were measured; (4) Micro-CT was used to accurately scan fresh bovine eyes and obtain the geometrical image and data to establish bovine eye model. 3-D reconstruction was performed using these images and data to work out the geometric shape of bovine eye; (5) IOP levels for eyeball FEM was set and the inner wall of eyeball was used taken as load-bearing part. Simulated eyeball FE modeling was run under the IOP level of 10 mmHg, 30 mmHg, 60 mmHg and 100 mmHg, and the force condition of different parts of eyeball was recorded under different IOP levels. RESULTS: (1) We obtained the material parameters more in line with physiological conditions and established a more realistic eyeball model using reversed engineering of parameters optimization method to calculate the complex nonlinear super-elastic and viscoelastic parameters more accurately; (2) We observed the following phenomenon by simulating increased pressure using FEM: as simulative IOP increased, the stress concentration scope on the posterior half of sclera became narrower; in the meantime, the stress-concentration scope on the anterior half of scleral gradually expanded, and the stress on the central part of LC is highest. CONCLUSION: As simulative IOP increased, stress-concentration scope on the posterior half of sclera gradually narrowed; in the meantime, the stress concentration scope on the anterior half of sclera gradually expanded, and the stress on the LC is mainly concentrated in the central part, suggesting that IOP is mainly concentrated in the anterior part of the eyeball as it increases. This might provide a biomechanical evidence to explain why RGCs in peripheral part die earlier than RGCs in central part under HIOP. PMID- 26268322 TI - Urgent need to reevaluate the latest World Health Organization guidelines for toxic inorganic substances in drinking water. AB - The World Health Organization (WHO) has established guidelines for drinking-water quality that cover biological and chemical hazards from both natural and anthropogenic sources. In the most recent edition of Guidelines for Drinking water Quality (2011), the WHO withdrew, suspended, did not establish, or raised guidelines for the inorganic toxic substances manganese, molybdenum, nitrite, aluminum, boron, nickel, uranium, mercury, and selenium. In this paper, we review these changes to the WHO drinking-water guidelines, examining in detail the material presented in the WHO background documents for each of these toxic substances. In some cases, these WHO background documents use literature reviews that do not take into account scientific research published within the last 10 or more years. In addition, there are instances in which standard WHO practices for deriving guidelines are not used; for example, rounding and other mathematical errors are made. According to published meeting reports from the WHO Chemical Aspects Working Group, the WHO has a timetable for revising some of its guidelines for drinking-water quality, but for many of these toxic substances the planned changes are minimal or will be delayed for as long as 5 years. Given the limited nature of the planned WHO revisions to the inorganic toxic substances and the extended timetable for these revisions, we suggest that governments, researchers, and other stakeholders might establish independent recommendations for inorganic toxic substances and possibly other chemicals to proactively protect public health, or at the very least, revert to previous editions of the Guidelines for Drinking-water Quality, which were more protective of public health. PMID- 26268323 TI - Serum inorganic phosphorus levels predict 30-day mortality in patients with community acquired pneumonia. AB - BACKGROUND: Community acquired pneumonia is a major cause of morbidity and mortality. The association between serum phosphorus levels on admission and the outcome of patients with community acquired pneumonia has not been widely examined. We aimed to investigate the prognostic value of serum phosphorus levels on admission on the 30- day mortality. METHODS: The cohort included patients of 18 years old or older who were diagnosed with community acquired pneumonia between 2006 and 2012. Patients were retrospectively analyzed to identify risk factors for a primary endpoint of 30-day mortality. Binary logistic regression analysis was used for the calculation of the odds ratios (OR) and p values in bivariate and multivariate analysis to identify association between patients' characteristic and 30-day mortality. RESULTS: The cohort included 3894 patients. In multivariate regression analysis, variables associated with increased risk of 30-day mortality included: age >80 years, increased CURB-65 score, RDW >15, hypernatremia >150 mmol/l, hypoalbuminemia <2 gr/dl and abnormal levels of phosphorus. Levels of <1.5 mg/dl and >4.5 mg/dl were significantly associated with excess 30-day mortality, 38 % (OR 2.9, CI 1.8-4.9, P = 0.001) and 39 % (OR 3.4, CI 2.7-4.2, P = 0.001), respectively. Phosphorus levels within the upper normal limits (4-4.5 mg/dl) were associated with higher mortality rates compared to levels between 1.5-3.5 mg/dl, the reference group, 24 % (OR 1.9, CI 1.5-2.4, P = 0.001). CONCLUSIONS: Abnormal phosphorus levels on admission are associated with increased mortality rates among patients hospitalized with Community acquired pneumonia. PMID- 26268324 TI - PEComa of the uterus with coexistence of situs inversus totalis, a case report and literature review. AB - PEComas are a group of very rare mesenchymal neoplasms, which express myogenic and melanocytic markers, such as HMB-45 and actin. Situs inversus totalis represents a complete left to right side transposition of the asymmetrical thoracic and abdominal organs and incorporates dextrocardia. The presence of uterus PEComa in the setting of situs inversus totalis is extremely rare. Here, we report a case of PEComa of uterus with coexistence of situs inversus totalis and review the literatures. To the best of our knowledge this is the fist report of a uterus PEComa patient with situs inversus totalis. PMID- 26268325 TI - Cytokine detection and simultaneous assessment of rheumatoid factor interference in human serum and synovial fluid using high-sensitivity protein arrays on plasmonic gold chips. AB - BACKGROUND: Fluorescence-enhancing microarray on plasmonic gold film is an attractive alternative to traditional enzyme-linked immunosorbent assay (ELISA) for cytokine detection because of the increased sensitivity. The assay chemistry is similar to an ELISA sandwich assay, but owing to the gold substrate, cytokine measurements are 10 to 100 times more sensitive and can be multiplexed. Plasmonic protein microarrays are, as other immunoassays, affected by the presence of heterophilic antibodies and rheumatoid factor may lead to analytical errors with serious implications for patient care. Here, we present a plasmonic gold substrate protein microarray for high-sensitivity detection of cytokines with simultaneous assessment of rheumatoid factor interference on a single chip. RESULTS: Paired serum and synovial fluid samples from patients with rheumatoid arthritis (n = 18), osteoarthritis (n = 9) or healthy controls (n = 10) were arrayed on near-infrared fluorescence enhancing plasmonic gold chips spotted with cytokine-specific capture antibody and isotype control antibody. Possible rheumatoid factor interference was visualised by a non-specific signal from the isotype control antibody, and pre-treatment of samples with heat-aggregated animal IgG eliminated this background contamination. The platform was optimised using the cytokine IL-20. The protein microarray platform allowed for the detection of human IL-20 at levels <1 pg/ml with reliable IL-20 quantification over a 5-log dynamic range. Samples for which rheumatoid factor caused artefacts were identified and a method for eliminating rheumatoid factor interference was developed and validated. IL-20 protein levels were significantly higher in synovial fluid samples from patients with rheumatoid arthritis compared to osteoarthritis (p < 0.001), while serum levels of IL-20 did not differ between patients with rheumatoid arthritis, osteoarthritis or healthy controls. CONCLUSION: Using novel plasmonic gold chips, we developed a highly sensitive and accurate assay platform to detect lowly expressed cytokines in biological fluids, allowing for the elimination of rheumatoid factor interference in as little as 5 MUl sample volume. The detection limit was below 1 pg/ml for IL-20 and linearity was achieved over a 5-log dynamic range. This technology is highly advantageous for cytokines where sensitivity or sample volume is critical or where assessment of rheumatoid factor interference needs addressed and eliminated. PMID- 26268326 TI - Mechanisms of Acupuncture Effect on Alzheimer's Disease in Animal- Based Researches. AB - Alzheimer's disease is the most common type of dementia in the aging population worldwide. The etiology and treatment of Alzheimer's disease are still not very clear. Finding a new treatment is urgent due to the increasing population aging. Acupuncture has been practicing in China for more than 3000 years and reported to be beneficial in treating cognitive impairment of Alzheimer's disease. This paper reviews the recent development on the effect of acupuncture on Alzheimer's disease in animal-based researches. It is suggested that acupuncture improves cognitive function of Alzheimer's disease by regulating glucose metabolism, enhancing neurotransmission as well as reducing oxidative stress, Abeta protein deposition, and neuronal apoptosis. However, it is still difficult to clarify which specific signaling pathway contributes to the acupuncture effect. Better designed studies are recommended to investigate the effects of acupuncture on Alzheimer's disease. PMID- 26268327 TI - Levetiracetam might act as an efficacious drug to attenuate cognitive deficits of Alzheimer's disease. AB - Levetiracetam is a homologue of piracetam with an a-ethyl side-chain substitution and it is a Food and Drug Administration (FDA) approved antiepileptic drug. Recently, several studies have found that levetiracetam was able to reduce seizure frequency in epileptic seizures patients without affecting their cognitive functions. In the present review, the effects of levetiracetam on cognitive improvement were summarized in epileptic seizures patients with or without Alzheimer's disease (AD), high-grade glioma (HGG) patients and amnestic mild cognitive impairment (aMCI) patients. In addition, levetiracetam was observed to improve the cognitive deficits in normal aged animals and the transgenic animal models with AD, suggesting that levetiracetam may be a better choice for the prevention or treatment of AD. PMID- 26268328 TI - Docosahexaenoic Acid-Phosphatidylcholine Improves Cognitive Deficits in an Abeta23-35-Induced Alzheimer's Disease Rat Model. AB - Both Docosahexaenoic acid (DHA) and Phosphatidylcholine (PC) have been shown to halt the pathogenesis of Alzheimer disease (AD) and vascular dementia. This study aimed to investigate the role of DHA-containing PC (DHA-PC) in the improvement of Abeta25-35-induced cognitive deficits in rats. Abeta25-35-induced AD rats were treated for 30 days with DHA-PC, which was extracted from Sthenoteuthis oualaniensis spawns. Cognitive improvement of the AD rats was detected using the Morris water maze (MWM). The results demonstrated that DHA-PC could improve the learning and memory abilities of AD rats in a dose-dependent pattern. Further analyses showed that expression of phosphorylated tau decreased, and the neuronal morphology recovered in brains of DHA-PC-treated AD rats, as compared with mock treated AD rats. In addition, DHAPC treatment increased the activity of GSH-Px and SOD in the cortex and hippocampus of AD rats. Taken together, these data suggest that DHA-PC is able to improve the cognitive deficits in AD rats, probably through decreasing the phosphorylation of tau in the cortex and hippocampus CA1 area, and increasing the GSH-Px and SOD activities in the brain of AD rats. PMID- 26268329 TI - Anti-Alzheimer Therapeutic Drugs Targeting gamma-Secretase. AB - gamma-secretase is a membrane-embedded aspartyl protease carrying out cleavage of more than 100 single transmembrane-spanning proteins, including APP, Notch, N cadherin, etc. Its subunit, presenilin (PS) is the catalytic component, of which mutations are a major cause of early onset familial Alzheimer disease (FAD). These mutations lead to an increase in the production of the highly amyloidogenic Abeta42 isoform. Drugs aimed at gamma-secretase are now considered to be promising therapeutic targets for AD. gamma-secretase inhibitors (GSIs) were first introduced into clinical trials due to their efficacy in lowering Abeta production, but later were found to cause severe adverse events due to their blockage of the Notch signaling process. gamma-secretase modulators (GSMs) were developed to modulate gamma-secretase activity by selectively targeting Abeta42 reduction over the Notch pathway, which have been shown to have less side effects. Although clinical studies show that none of the GSIs or GSMs have been proven to be fully effective, they shed light on the physiological role of gamma secretase and PS in AD development. At the same time, natural products, due to their structural diversity and pleiotropic profile, can modulate gamma-secretase activity in a dose-dependent manner, broadening our vision of drug development. With the structural information of gamma-secretase released recently, we speculate there will be an explosion of gamma-secretase modulators targeting not only the proteolysic center but also the interaction of its different components. PMID- 26268330 TI - Multi-Target Strategy and Experimental Studies of Traditional Chinese Medicine for Alzheimer's Disease Therapy. AB - Alzheimer's disease (AD) is a multifactorial complex disease. The pathogenesis of AD is very complicated, and involves the beta-amyloid (Abeta) cascade, tau hyperphosphorylation, neuroinflammation, oxidative stress, mitochondrial dysfunction, reduced levels of neurotrophic factors, and damage and loss of synapses as well as cholinergic neurons. The multi-target characteristics of traditional Chinese medicine (TCM) may be advantageous over single-target drugs in the treatment of complex diseases. These drugs have therefore attracted more attention in the research and development of AD therapies. This review describes advances made in experimental studies of TCM for AD treatment. It discusses research, from our group and other laboratories, on TCM compound drugs (Shenwu capsule) and approximately 10 Chinese medicinal herb extracts (tetrahydroxystilbene glucoside, epimedium flavonoid, icariin, cornel iridoid glycoside, ginsenoside, puerarin, clausenamide, huperzine A, and timosaponins). PMID- 26268331 TI - Ginseng for Alzheimer's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. AB - BACKGROUND: There is no curative treatment for Alzheimer's disease (AD). Ginseng is widely used in the treatment of AD in Asian countries. OBJECTIVE: To evaluate the effectiveness and safety of ginseng for AD. METHODS: We searched seven main databases for randomized clinical trials (RCTs) on ginseng for AD from their inception to December 2014. The Cochrane risk of bias tool was used to assess the methodological quality. We used RevMan 5.2 to synthesize the results. RESULTS: Four RCTs involving 259 participants were identified for this systematic review. The methodological quality of included studies was not promising. All comparisons were made between combined treatment (ginseng plus conventional treatment) versus conventional treatment. The results of meta-analyses and several individual studies showed that the effectiveness of combined treatment was inconsistent as measured by MMSE, ADAS-cog, ADAS-noncog, and CDR. No studies reported the outcomes of quality of life (QoL). The current data did not report serious adverse events. CONCLUSION: This review showed that the effects of ginseng on AD were still inconclusive. The main limitations of the available studies were small sample sizes, poor methodological qualities and no placebo controls. Larger, well designed studies are needed to test the effect of ginseng on AD in the future. PMID- 26268332 TI - Ginkgo Biloba for Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. AB - BACKGROUND: Ginkgo biloba is a natural medicine used for cognitive impairment and Alzheimer's disease. The objective of this review is to explore the effectiveness and safety of Ginkgo biloba in treating mild cognitive impairment and Alzheimer's disease. METHODS: Electronic search was conducted from PubMed, Cochrane Library, and four major Chinese databases from their inception up to 1(st) December, 2014 for randomized clinical trials on Ginkgo biloba in treating mild cognitive impairment or Alzheimer's disease. Meta-analyses were performed by RevMan 5.2 software. RESULTS: 21 trials with 2608 patients met the inclusion criteria. The general methodological quality of included trials was moderate to poor. Compared with conventional medicine alone, Ginkgo biboba in combination with conventional medicine was superior in improving Mini-Mental State Examination (MMSE) scores at 24 weeks for patients with Alzheimer's disease (MD 2.39, 95% CI 1.28 to 3.50, P<0.0001) and mild cognitive impairment (MD 1.90, 95% CI 1.41 to 2.39, P<0.00001), and Activity of Daily Living (ADL) scores at 24 weeks for Alzheimer's disease (MD -3.72, 95% CI -5.68 to -1.76, P=0.0002). When compared with placebo or conventional medicine in individual trials, Ginkgo biboba demonstrated similar but inconsistent findings. Adverse events were mild. CONCLUSION: Ginkgo biloba is potentially beneficial for the improvement of cognitive function, activities of daily living, and global clinical assessment in patients with mild cognitive impairment or Alzheimer's disease. However, due to limited sample size, inconsistent findings and methodological quality of included trials, more research are warranted to confirm the effectiveness and safety of ginkgo biloba in treating mild cognitive impairment and Alzheimer's disease. PMID- 26268333 TI - Long non-coding RNAs in Alzheimer's disease. AB - Alzheimer's disease (AD) is a neurodegenerative disorder with progressive damage to brain cells. It is the leading cause of dementia worldwide that is characterized by impairment of memory and eventually by reasoning and perception disturbances. No curative treatment for dementia is currently available. With the progress of RNA sequencing and transcriptome analysis, the discovery of non protein coding RNAs expands our knowledge about the genome. Long non-coding RNAs (lncRNAs) which are involved in a wide variety of biological processes as regulatory molecule, have been the focus of much recent research. In this review, we focus on the emerging roles of these lncRNAs in the pathology of Alzheimer's disease. Their expressions are brain-specific and dysregulated in the patient and animal model. Here, we will summarize the pathological features influenced by lncRNAs and therefore provide an lncRNA point-of-view on AD. This should stimulate new research directions and therapeutic options considering lncRNAs as novel prognostic markers and therapeutic targets. PMID- 26268334 TI - The Essential Mechanisms of Aging: What Have We Learnt in Ten Years? AB - Carbonylation due to oxidation and glycation is an important biochemical cause of degenerative diseases and aging. While the enigma of aging is understood as a result of molecular dysfunction due to the failure of maintenance systems, a brief history of the interpretation of aging mechanisms and the exact biochemistry connecting entropy and biological aging is addressed. Lipofuscin formation mechanisms resulting in irreparable accumulative changes represent the most important aging- related alterations of entropy increase in biological kingdom, which is very different from the damage-based "aging" process of inorganic materials. A fifth level of aging mechanism investigations that highlights the importance of functional groups of biochemistry, the "missing codes" of life science, is put forward in this review. Significance and validities of such 'life codes' in biology beyond genomic and proteomic concepts has also been clarified. An open-minded consideration of functional groups of biomolecules, such as carbonyl groups, may help to explain the mechanisms of fatigue and sleep in terms of neurobiochemistry and biological pharmaco-medicine. PMID- 26268335 TI - Energy Metabolism, Adult Neurogenesis and their Possible Roles in Alzheimer's Disease: A Brief Overview. AB - Alzheimer's disease (AD) is the most prevalent human neurodegenerative disease. Disturbances of brain glucose uptake, glucose tolerance, glucose utilization and of the insulin/insulin receptor signaling cascade are thought to be key features of the pathophysiology of AD. Changes in energy homeostasis in the brain and in the periphery dramatically influence the proliferation of adult neural stem cells and neurogenesis in the hippocampus. Recent findings suggest that adult neurogenesis is altered in the hippocampus of AD patients and in various animal models of AD. Several factors associated with the pathogenesis of AD are also known to be involved in the regulation of adult neurogenesis. Understanding the mechanisms underlying these changes at different stages of AD could provide insights into its pathogenesis, contribute to identifying biomarkers of early AD, and supply fundamental knowledge that will allow novel therapeutic approaches to treating AD by intervening in adult neurogenesis. In this review we provide an overview of the connections between energy metabolism, adult neurogenesis and AD. PMID- 26268336 TI - Targeting Insulin Signaling for the Treatment of Alzheimer's Disease. AB - Sporadic Alzheimer's disease (AD) is caused by multiple etiological factors, among which impaired brain insulin signaling and decreased brain glucose metabolism are important metabolic factors. Contrary to previous belief that insulin would not act in the brain, studies in the last three decades have proven important roles of insulin and insulin signaling in various biological functions in the brain. Impaired brain insulin signaling or brain insulin resistance and its role in the molecular pathogenesis of sporadic AD have been demonstrated. Thus, targeting brain insulin signaling for the treatment of cognitive impairment and AD has now attracted much attention in the field of AD drug discovery. This article reviews recent studies that target brain insulin signaling, especially those investigations on intranasal insulin administration and drugs that improve insulin sensitivity, including incretins, dipeptidyl peptidase IV inhibitors, thiazolidinediones, and metformin. These drugs have been previously approved for the treatment of diabetes mellitus, which could expedite their development for the treatment of AD. Although larger clinical trials are needed for validating their efficacy for the treatment of cognitive impairment and AD, results of animal studies and clinical trials available to date are encouraging. PMID- 26268337 TI - Formaldehyde as a trigger for protein aggregation and potential target for mitigation of age-related, progressive cognitive impairment. AB - Recently, formaldehyde (FA), existing in a number of different cells including neural cells, was found to affect age-related cognitive impairment. Oral administration of methanol (the metabolic precursor of FA) triggers formation of senile plaques (SPs) and Tau hyperphosphorylation in the brains of monkeys with memory decline. Intraperitoneal injection of FA leads to hyperphosphorylation of Tau in wild-type mouse brains and N2a cells through activation of glycogen synthase kinase-3beta (GSK-3beta). Furthermore, formaldehyde at low concentrations can directly induce Tau aggregation and amyloid beta (Abeta) peptide deposits in vitro. Formaldehyde-induced Tau aggregation is implicated in cytotoxicity and neural cell apoptosis. Clarifying how FA triggers Abeta deposits and Tau hyperphosphorlyation will not only improve our understanding of the molecular and cellular mechanisms of age-related cognitive impairment but will also contribute to the ongoing investigation of alternate targets for new drugs. Here, we review the role of FA, particularly that of endogenous origin, in protein aggregation and as a potential drug intervention in the development of agerelated cognitive impairment. PMID- 26268338 TI - In Vitro Inhibition of Glyoxalase I by Flavonoids: New Insights from Crystallographic Analysis. AB - The antitumor pharmacological property of flavonoids is correlated with inhibition towards glyoxalase I (GLOI), a critical zinc-enzyme in the methylglyoxal detoxification pathway. In this study, 16 flavonoids were examined, and only baicalein (Ki of 0.183 uM) is identified as a potent in vitro GLOI inhibitor. X-ray crystallographic analysis reveals that baicalein chelates with the catalytic Zn(2+) via its characteristic C6/C7 hydroxyl groups. The coordination ability of flavonoids, and therefore their ability to inhibit GLOI, is determined by the Zn(2+) coordination geometry, the rigid skeleton of flavonoids and the geometry of the hydrophobic cavity of the GLOI active site. This structural basis could be useful in predicting GLOI inhibition of other natural polyphenols. PMID- 26268339 TI - Non-Zinc-Binding Inhibitors of MMP-13: GRID-Based Approaches to Rationalize the Binding Process. AB - Matrix metalloproteinases (MMPs) are zinc enzymes responsible for the degradation of the extracellular matrix. With this function, MMPs are involved in many physiological processes, but also in many pathological states. MMP-13 is implicated in the degradation of type II collagen, the main structural protein of articular cartilage, contributing to the development of osteoarthritis and inflammatory diseases. In the last years, a new generation of potent and selective MMP inhibitors (MMPIs) has been identified and classified as non-zinc binding inhibitors (NZBIs). Several MMP-13 NZBIs have been developed and crystallographically determined in complex with the enzyme. Here, we provide a detailed review of the current knowledge about this class of MMP-13 inhibitors and, by using computational procedures, we highlight the molecular determinants that are needed for the binding process. In particular, FLAP, a program based on GRID molecular interaction fields, was used to analyze the ligand-protein interactions: molecular shape and hydrogen bond acceptor groups strongly influence the binding according to the ligand-based modeling, while the aromatic interactions are better identified by the structure-based study. The complementary results can be combined in a high performance model, showing the effectiveness of molecular interaction field based approaches to search for novel MMP-13 NZBIs. PMID- 26268340 TI - Novel HIV-1 Integrase Inhibitor Development by Virtual Screening Based on QSAR Models. AB - HIV-1 integrase (IN) plays an important role in the life cycle of HIV and is responsible for integration of the virus into the human genome. We present computational approaches used to design novel HIV-1 IN inhibitors. We created an IN inhibitor database by collecting experimental data from the literature. We developed quantitative structure-activity relationship (QSAR) models of HIV-1 IN strand transfer (ST) inhibitors using this database. The prediction accuracy of these models was estimated by external 5-fold cross-validation as well as with an additional validation set of 308 structurally distinct compounds from the publicly accessible BindingDB database. The validated models were used to screen a small combinatorial library of potential synthetic candidates to identify hits, with a subsequent docking approach applied to further filter out compounds to arrive at a small set of potential HIV-1 IN inhibitors. As result, 236 compounds with good druglikeness properties and with correct docking poses were identified as potential candidates for synthesis. One of the six compounds finally chosen for synthesis was experimentally confirmed to inhibit the ST reaction with an IC50(ST) of 37 uM. The IN inhibitor database is available for download from http://cactus.nci.nih.gov/download/iidb/. PMID- 26268341 TI - 6,7-Dihydroxyisoindolin-1-one and 7,8-Dihydroxy-3,4-Dihydroisoquinolin- 1(2H)-one Based HIV-1 Integrase Inhibitors. AB - Integrase (IN) is an essential viral enzyme required for HIV-1 replication, which has been targeted by anti-AIDS therapeutics. Integrase strand transfer inhibitors (INSTIs) represent a new class of antiretroviral agents developed for the treatment of HIV-1 infections. Important structural features that are shared by many INSTIs include a coplanar arrangement of three heteroatoms that chelate two catalytic Mg(2+) ions in the IN active site and a linked halophenyl ring that binds in the hydrophobic pocket formed by the complex of IN with viral DNA. We recently reported bicyclic 6,7-dihydroxyoxoisoindolin-1-one-based IN inhibitors. In the current study, we modified these inhibitors in three ways. First, we increased the spacer length between the metalchelating triad and the halophenyl group. Second, we replaced the indoline [5,6] bicycle with a fused dihydroxyisoquinolinones [6,6] ring system. Finally, we prepared bis-6,7 dihydroxyisoindolin-1-one-4-sulfonamides as dimeric HIV-1 IN inhibitors. These new analogues showed low micromolar inhibitory potency in in vitro HIV-1 integrase assays. PMID- 26268342 TI - Panobinostat: The Small Molecule Metalloenzyme Inhibitor with Marvelous Anticancer Activity. AB - Histone acetyl transferases (HATs) and histone deacetylases (HDACs) are antagonistic enzymes regulating the turnover of histone acetylation thereby governing gene expression in a precise manner. Histone acetylation deregulation caused by aberrant expression of classical HDACs plays a crucial role in tumour onset and progression making these enzymes as striking targets for anticancer drugs and therapy. Small molecule inhibitors targetting HDACs (HDACi) have shown multiple biological effects including cell cycle arrest, differentiation and apoptosis in cancer cell models. The current review deals with the recently approved pan-HDAC inhibitor panobinostat (LBH589) and its antiproliferative activity against distinct cancers (breast, ovarian, lung and multiple myeloma). The intricate details about the different mechanisms triggered by panobinostat to exert cytotoxic effect in these cancers have also been provided. The article also highlights the different combination strategies of panobinostat which can be utilized for overcoming conventional therapy resistant cases and for achieving the enhanced therapeutic benefit from this marvelous inhibitor in the upcoming future. PMID- 26268343 TI - Selective Histone Deacetylase Inhibitors with Anticancer Activity. AB - HDAC inhibitors (HDACIs), which can be used to kill cancer cells through inhibiting histone deacetylase activity or altering the structure of chromatin, have emerged as efficacious agents in the treatment of cancer. With SAHA, FK228, belinostat and panobinostat approved by the FDA, displaying satisfying activity in both haematological and solid tumors of various tissues, efforts to create selective HDACIs have been attracted attention over the past several years. Herein, we mainly review the progress of selective HDAC inhibitors including class-selective and isoform-selective HDAC inhibitors. PMID- 26268345 TI - Metalloprotein Inhibitors for the Treatment of Human Diseases. AB - Metalloproteins have attracted momentous attentions for the treatment of many human diseases, including cancer, HIV, hypertension, etc. This article reviews the progresses that have been made in the field of drug development of metalloprotein inhibitors, putting emphasis on the targets of carbonic anhydrase, histone deacetylase, angiotensin converting enzyme, and HIV-1 integrase. Many other important metalloproteins are also briefly discussed. The binding and coordination modes of different marketed metalloprotein inhibitors are stated, providing insights to design novel metal binding groups and further novel inhibitors for metalloproteins. PMID- 26268344 TI - Advances in Bacterial Methionine Aminopeptidase Inhibition. AB - Methionine aminopeptidases (MetAPs) are metalloenzymes that cleave the N-terminal methionine from newly synthesized peptides and proteins. These MetAP enzymes are present in bacteria, and knockout experiments have shown that MetAP activity is essential for cell life, suggesting that MetAPs are good antibacterial drug targets. MetAP enzymes are also present in the human host and selectivity is essential. There have been significant structural biology efforts and over 65 protein crystal structures of bacterial MetAPs are deposited into the PDB. This review highlights the available crystallographic data for bacterial MetAPs. Structural comparison of bacterial MetAPs with human MetAPs highlights differences that can lead to selectivity. In addition, this review includes the chemical diversity of molecules that bind and inhibit the bacterial MetAP enzymes. Analysis of the structural biology and chemical space of known bacterial MetAP inhibitors leads to a greater understanding of this antibacterial target and the likely development of potential antibacterial agents. PMID- 26268346 TI - Isotopic Preferential Solvation of I(-) in Low-Temperature Water Nanoclusters. AB - We present results from ring polymer molecular dynamics experiments that provide microscopic insights into the characteristics of the isotopic stabilizations of H and D aqueous species in the first solvation shell of a halide I(-) ion in water nanoclusters at low temperatures. The analysis of the simplest I(-).(HOD) dimer shows a clear propensity for the light isotope to lie at the non-hydrogen-bonded dangling position. Our results predict that, at T ~ 50 K, I(-).(DOH) isomers are three times more abundant than I(-).(HOD) ones. The reasons for such stabilization can be traced back to differences in the nuclear kinetic energy projected along directions perpendicular to the plane of the water molecule. Dynamical implications of these imbalances are shown to be reflected in the characteristics of the corresponding bands of the infrared spectroscopic signals. A similar analysis performed in larger aggregates containing ~20 water molecules reveals, in contrast, a stabilization of the light isotope along I(-)...HO hydrogen bonds. Effects derived from the consideration of smaller halide anions with larger electric fields at the surface are also examined. PMID- 26268347 TI - From arterial hypertension complications to von Hippel-Lindau syndrome diagnosis. AB - Von Hippel-Lindau syndrome is a rare, genetically based, autosomal dominant disorder. Its course is accompanied by the development of multiple neoplasms with the following tumours diagnosed most commonly in the central nervous system haemangioblastoma, clear cell renal cell carcinoma, phaeochromocytomas, pancreatic islet tumours, and endolymphatic sac tumours. Additionally, renal and pancreatic cystadenomas and epididymal cystadenomas have been diagnosed in males and cystadenomas of the broad ligament of the uterus have been diagnosed in females.The following paper presents the diagnostic way in a boy with vision disorders as the first symptom. Hypertension retinopathy and extremely elevated blood pressure were observed during ophthalmologic consultation. Complications of arterial hypertension were confirmed by echocardiography, which diagnosed hypertension cardiomyopathy. Hypertension retinopathy was confirmed by optical coherence tomography. Examinations performed in the neurology, cardiology, and finally endocrinology indicated a bilateral phaeochromocytoma as the cause of arterial hypertension. Moreover, some genetic investigations showed a mutation in the VHL ex.1 p.Y112 C gene responsible for the hereditary form of phaeochromocytoma which confirmed von Hippel-Lindau syndrome. After surgical treatment of phaeochromocytoma the patient needed careful management according to the surveillance protocol for von Hippel-Lindau disease. PMID- 26268348 TI - No neuropathological evidence for a direct topographical relation between microbleeds and cerebral amyloid angiopathy. AB - INTRODUCTION: Cerebral microbleeds correspond to blood breakdown products, including hemosiderin-containing macrophages around small vessels on histological examination. Superficial lobar cerebral microbleeds are increasingly recognized on MRI as a biomarker of cerebral amyloid angiopathy but the direct association between amyloid-laden vessels burden and cerebral microbleeds has yet to be validated neuropathologically. To address this issue, we examined the frequency of histopathologically-defined cerebral microbleeds in different brain regions and their relationship with cerebral amyloid angiopathy in a large autopsy population. RESULTS: The frontal, parietal and occipital cortex as well as the adjacent white matter and basal ganglia of 113 consecutive autopsies were examined. Cerebral microbleedss were identified on haematoxylin-eosin-stained histological slides, cerebral amyloid angiopathy using anti-amyloid antibody. Cerebral microbleeds were present in 92.9 % of the cases and cerebral amyloid angiopathy in 44.3 % of them. Cerebral microbleeds were more frequent in parietal and frontal lobes followed by the occipital region and basal ganglia. In contrast, cerebral amyloid angiopathy was most frequent in the occipital lobe. There was no significant topographical association between cerebral amyloid angiopathy presence or severity and cerebral microbleeds in any brain region. In lobar areas, cerebral amyloid angiopathy was found in the cortex, predominantly affecting pial arteries and their superficial cortical branches, in contrast to microbleeds which were mainly in the white matter and occurred around deeper arteries and arterioles, including the subcortical segment of long penetrating branches of pial vessels. CONCLUSIONS: Our study does not support a direct relation between cerebral microbleeds and cerebral amyloid angiopathy burden at the neuropathological level, raising intriguing questions on the potential pathophysiological mechanisms of cerebral microbleeds in the context of cerebral amyloid angiopathy or other small vessel disease pathology. PMID- 26268349 TI - SEND: a system for electronic notification and documentation of vital sign observations. AB - BACKGROUND: Recognising the limitations of a paper-based approach to documenting vital sign observations and responding to national clinical guidelines, we have explored the use of an electronic solution that could improve the quality and safety of patient care. We have developed a system for recording vital sign observations at the bedside, automatically calculating an Early Warning Score, and saving data such that it is accessible to all relevant clinicians within a hospital trust. We have studied current clinical practice of using paper observation charts, and attempted to streamline the process. We describe our user focussed design process, and present the key design decisions prior to describing the system in greater detail. RESULTS: The system has been deployed in three pilot clinical areas over a period of 9 months. During this time, vital sign observations were recorded electronically using our system. Analysis of the number of observations recorded (21,316 observations) and the number of active users (111 users) confirmed that the system is being used for routine clinical observations. Feedback from clinical end-users was collected to assess user acceptance of the system. This resulted in a System Usability Scale score of 77.8, indicating high user acceptability. CONCLUSIONS: Our system has been successfully piloted, and is in the process of full implementation throughout adult inpatient clinical areas in the Oxford University Hospitals. Whilst our results demonstrate qualitative acceptance of the system, its quantitative effect on clinical care is yet to be evaluated. PMID- 26268350 TI - Distribution and diversity of ribosome binding sites in prokaryotic genomes. AB - BACKGROUND: Prokaryotic translation initiation involves the proper docking, anchoring, and accommodation of mRNA to the 30S ribosomal subunit. Three initiation factors (IF1, IF2, and IF3) and some ribosomal proteins mediate the assembly and activation of the translation initiation complex. Although the interaction between Shine-Dalgarno (SD) sequence and its complementary sequence in the 16S rRNA is important in initiation, some genes lacking an SD ribosome binding site (RBS) are still well expressed. The objective of this study is to examine the pattern of distribution and diversity of RBS in fully sequenced bacterial genomes. The following three hypotheses were tested: SD motifs are prevalent in bacterial genomes; all previously identified SD motifs are uniformly distributed across prokaryotes; and genes with specific cluster of orthologous gene (COG) functions differ in their use of SD motifs. RESULTS: Data for 2,458 bacterial genomes, previously generated by Prodigal (PROkaryotic DYnamic programming Gene-finding ALgorithm) and currently available at the National Center for Biotechnology Information (NCBI), were analyzed. Of the total genes examined, ~77.0% use an SD RBS, while ~23.0% have no RBS. Majority of the genes with the most common SD motifs are distributed in a manner that is representative of their abundance for each COG functional category, while motifs 13 (5'-GGA 3'/5'-GAG-3'/5'-AGG-3') and 27 (5'-AGGAGG-3') appear to be predominantly used by genes for information storage and processing, and translation and ribosome biogenesis, respectively. CONCLUSION: These findings suggest that an SD sequence is not obligatory for translation initiation; instead, other signals, such as the RBS spacer, may have an overarching influence on translation of mRNAs. Subsequent analyses of the 5' secondary structure of these mRNAs may provide further insight into the translation initiation mechanism. PMID- 26268351 TI - Patients presenting with acute poisoning to an outpatient emergency clinic: a one year observational study in Oslo, Norway. AB - BACKGROUND: In Oslo, the majority of patients with acute poisoning are treated in primary care, at an emergency outpatient clinic with limited diagnostic and treatment resources. We describe the poisonings currently seen in this setting. We compare our findings with previous studies, with special concern for the appearance of new toxic agents, and changes in overall numbers and patterns of poisoning. METHODS: Observational study. Patients above the age of 12 years presenting at Oslo Accident and Emergency Outpatient Clinic (Oslo Legevakt) with acute poisoning were included consecutively from October 2011 through September 2012. Physicians and nurses registered data on preset forms. Main outcome measures were toxic agents, age, sex, intention, referral and time of presentation. RESULTS: There were 2923 episodes of acute poisoning in 2261 patients. Median age of the patients was 32 years, and 1430 (63%) were males. The most frequent toxic agents were ethanol in 1684 (58%) episodes, heroin in 542 (19 %), benzodiazepines in 521 (18%), amphetamine in 275 (9%), fire smoke in 192 (7%), gamma-hydroxybutyrate (GHB) in 144 (5%), and cannabis in 143 (5%). In 904 (31%) poisonings there were more than one toxic agent. In 493 episodes (17%), the patient was hospitalised, and in 60 episodes (2%) admitted to a psychiatric ward. Most poisonings, 2328 (80%), were accidental overdoses with substances of abuse, 276 (9%) were suicide attempts, and 312 (11%) were accidents. Among ethanol poisonings in patients above the age of 26 years, 685/934 (73%) were in males, and 339/934 (36%) presented during weekends. However, among ethanol poisonings in patients under the age of 26 years, 221/451 (49 ) were in females, and 297/451 (66%) presented during weekends. CONCLUSIONS: The poisonings treated in this primary care setting were mostly due to accidental overdoses with ethanol or other substances of abuse. There is a disconcerting weekend drinking pattern among adolescents and young adults, with young females presenting as often as young males with ethanol poisoning. PMID- 26268353 TI - Attention-level transitory response: a novel hybrid BCI approach. AB - OBJECTIVE: People with disabilities may control devices such as a computer or a wheelchair by means of a brain-computer interface (BCI). BCI based on steady state visual evoked potentials (SSVEP) requires visual stimulation of the user. However, this SSVEP-based BCI suffers from the 'Midas touch effect', i.e., the BCI can detect an SSVEP even when the user is not gazing at the stimulus. Then, these incorrect detections deteriorate the performance of the system, especially in asynchronous BCI because ongoing EEG is classified. In this paper, a novel transitory response of the attention-level of the user is reported. It was used to develop a hybrid BCI (hBCI). APPROACH: Three methods are proposed to detect the attention-level of the user. They are based on the alpha rhythm and theta/beta rate. The proposed hBCI scheme is presented along with these methods. Hence, the hBCI sends a command only when the user is at a high-level of attention, or in other words, when the user is really focused on the task being performed. The hBCI was tested over two different EEG datasets. MAIN RESULTS: The performance of the hybrid approach is superior to the standard one. Improvements of 20% in accuracy and 10 bits min(-1) are reported. Moreover, the attention level is extracted from the same EEG channels used in SSVEP detection and this way, no extra hardware is needed. SIGNIFICANCE: A transitory response of EEG signal is used to develop the attention-SSVEP hBCI which is capable of reducing the Midas touch effect. PMID- 26268352 TI - Restrictive IgG antibody response against mutated citrullinated vimentin predicts response to rituximab in patients with rheumatoid arthritis. AB - INTRODUCTION: Antibodies against mutated citrullinated vimentin (AMCV) represent a useful diagnostic marker with correlation to disease activity in patients with rheumatoid arthritis (RA). Since seropositivity for citrullinated autoantibodies was predictive for response to B-cell depleting therapy (BCDT) with rituximab (RTX), we investigated whether differences in antibody fine reactivity and immunoglobulin (Ig) isotype kinetics among AMCV-positive patients could provide additional information about outcome. METHODS: A total of 50 AMCV IgG-positive RA patients (RTX responders (RRs) n = 37 and non-responders (NRRs) n = 13) were analyzed for reactivity against MCV epitopes and co-existent AMCV isotypes IgM and IgA. Antibody titers were determined by enzyme-linked immunosorbent assay at baseline and 24 weeks after the first cycle of RTX, and compared to kinetics of rheumatoid factor (RF) and antibodies against cyclic citrullinated peptide (ACCP). RESULTS: Recognized MCV epitopes by AMCV IgG of RRs and NRRs showed similar baseline patterns, with reducing reactivity in RRs and unchanged or even expanding reactivity in NRRs upon RTX treatment. At baseline, RRs were more frequently negative for AMCV subtypes, especially for IgA (68%), compared to NRRs (31%). Being AMCV IgA-negative at baseline indicated a good treatment response to RTX (negative predictive value = 0.86). Co-existence of AMCV IgA and IgG with stable titers upon treatment were associated with poorer responses to RTX. Furthermore, reductions of AMCV IgA levels upon RTX correlated with the improvement of 28-joint Disease Activity Score (DAS28). In comparison, subtypes of RF and ACCP were not of additional value for prediction of RTX response. CONCLUSIONS: Restrictive IgG seropositivity against MCV with treatment-associated decline in fine reactivity and titers was predictive for response to RTX. Double positivity for AMCV IgG and IgA was associated with failure to respond to BCDT, suggesting a pathogenetic and less sensitive IgA-producing B-cell subset in NRRs. PMID- 26268354 TI - Molecular and phenotypic distinction of the very recently evolved insular subspecies Mus musculus helgolandicus ZIMMERMANN, 1953. AB - BACKGROUND: Populations and subspecies of the house mouse Mus musculus were able to invade new regions worldwide in the wake of human expansion. Here we investigate the origin and colonization history of the house mouse inhabiting the small island of Heligoland on the German Bight - Mus musculus helgolandicus. It was first described by Zimmermann in 1953, based on morphological descriptions which were considered to be a mosaic between the subspecies M. m. domesticus and M. m. musculus. Since mice on islands are excellent evolutionary model systems, we have focused here on a molecular characterization and an extended phenotype analysis. RESULTS: The molecular data show that the mice from Heligoland are derived from M. m. domesticus based on mitochondrial D-loop sequences as well as on four nuclear diagnostic markers, including one each from the sex-chromosomes. STRUCTURE analysis based on 21 microsatellite markers assigns Heligoland mice to a distinct population and D-loop network analysis suggests that they are derived from a single colonization event. In spite of mice from the mainland arriving by ships, they are apparently genetically refractory against further immigration. Mutation frequencies in complete mitochondrial genome sequences date the colonization age to approximately 400 years ago. Complete genome sequences from three animals revealed a genomic admixture with M. m. musculus genomic regions with at least 6.5% of the genome affected. Geometric morphometric analysis of mandible shapes including skull samples from two time points during the last century suggest specific adaptations to a more carnivorous diet. CONCLUSIONS: The molecular and morphological analyses confirm that M. m. helgolandicus consists of a distinct evolutionary lineage with specific adaptations. It shows a remarkable resilience against genetic mixture with mainland populations of M. m. domesticus despite major disturbances in the past century and a high ship traffic. The genomic admixture with M. m. musculus genetic material may have contributed to the genomic distinction of the Heligoland mice. In spite of its young age, M. m. helgolandicus may thus be considered as a true subspecies of Mus, whose evolution was triggered through fast divergence on a small island. PMID- 26268356 TI - Role of B-scan ultrasonography in the localization of intraocular foreign bodies in the anterior segment: a report of three cases. AB - BACKGROUND: The accurate localization of intraocular foreign bodies (IOFBs) is very important for the management of ocular trauma patients. B-scan ultrasonography is usually used to detect IOFBs in the posterior segment. Here, we report three cases with IOFBs in the anterior segment near the posterior lens capsule, which were accurately localized by B-scan ultrasonography under dynamic transversal scanning. CASE PRESENTATION: All three patients had a history of ocular trauma, and their clinical symptoms were compatible with the persistence of IOFBs. It was difficult to get a direct visualization of IOFBs with slit-lamp biomicroscopy because of opacities of the cornea and traumatic cataract. A computed tomography scan detected IOFBs in the anterior segment, but could not determine the exact location. Ultrasound biomicroscopy was performed but failed to show any IOFBs owing to the limited depth of penetration. B-scan ultrasonography was further applied but also failed to show any intraocular foreign bodies using axial scanning, a routine procedure of B-scan ultrasonography examination. However, using dynamic transversal scanning of B scan ultrasonography, the accurate location of IOFBs was eventually shown to be embedded in the posterior lens cortex in case 1, adjacent to the posterior lens capsule in case 2, and located in the anterior vitreous close to the posterior lens capsule in case 3. Different surgical procedures were designed according to localization by B-scan ultrasonography, and all IOFBs were successfully removed. CONCLUSION: B-scan ultrasonography is a simple and effective imaging modality in the localization of IOFBs in traumatic cataract. Transversal scanning is more suitable than axial scanning to detect IOFBs in the anterior segment near the posterior lens capsule. PMID- 26268355 TI - Molecular characterisation of hepatitis B virus in HIV-1 subtype C infected patients in Botswana. AB - BACKGROUND: Hepatitis B virus (HBV) is a major global health problem especially in sub-Saharan Africa and in East Asia. Ten hepatitis B virus genotypes have been described that differ by geographic distribution, disease progression, and response to treatment. Escape mutations within the surface open reading frame (ORF) affect HBV antigenicity leading to failures in diagnosis, vaccine and hepatitis B immunoglobulin therapy. However, the molecular characteristics of HBV in Botswana, a highly endemic country, are unknown. We describe the molecular characteristics of HBV and prevalence of escape mutants among HIV/HBV coinfected individuals Botswana. METHODS: DNA was extracted from archived plasma samples from 81 HIV/HBV co-infected participants from various clinical studies at the Botswana Harvard AIDS Institute Partnership. A 415 base pair (bp) fragment of the polymerase gene was amplified by semi-nested PCR. In a subset of samples, a 2100 bp fragment was amplified. The PCR product was genotyped using Big Dye sequencing chemistry and the sequences were analysed for genotypes and mutations. RESULTS: Of the 81 samples included, 70 (86 %) samples were successfully genotyped. Genotype A was found in 56 (80 %) participants, D in 13 (18.6 %), and 1 (1.4 %) was genotype E. Escape mutations previously linked with failure of diagnosis or escaping active vaccination and passive immunoglobulin therapy were detected in 12 (17.1 %) participants at positions 100, 119, 122, 123, 124, 126, 129, 130, 133, 134 and 140 of the S ORF. Genotypes and escape mutations were not significantly associated with aspartate aminotransferase (AST), alanine aminotransferase (ALT) and AST platelet ratio index (APRI). CONCLUSION: Genotypes A, D and E were found in this cohort of HIV coinfected patients in Botswana, consistent with the findings from the sub-Saharan Africa region. Some escape mutations which have previously been associated with diagnosis failure, escaping vaccine and immunoglobulin therapy were also observed and are important in guiding future policies related to vaccine implementation, therapeutic guidelines, and diagnostic guidelines. They are also important for identifying patients who are at an increased risk of disease progression and to choose optimal therapy. Future research should focus on determining the clinical significance of the different HBV genotypes and mutations found in this population. PMID- 26268357 TI - Health-related quality of life from the perspective of children with severe specific language impairment. AB - BACKGROUND: This study aimed to evaluate the feasibility and reliability of the Pediatric Quality of Life Inventory(TM) 4.0 Generic Core Scales (PedsQL(TM)) for use by children with severe specific language impairment (SLI) and their parent, and to explore the health-related quality of life of children with severe SLI. We hypothesized that the PedsQL(TM) would be a suitable measure, and identify lower health-related quality of life compared to the healthy population sample, particularly in school and social functioning. METHODS: Forty-three out of 61 children with severe SLI enrolled at a dedicated school from February 2010 until September 2011 agreed to participate. Children and parents completed the PedsQL(TM) separately with support as required. RESULTS: The PedsQL(TM) proved to be suitable for this cohort. Children perceived themselves to be at risk of impaired social and physical functioning, rendering the total score below the population mean. Parents rated social and emotional functioning at risk of impairment, with the psychosocial and total summary score consequently below the population mean. Physical functioning had the largest child/parent difference, with children rating themselves below the cut-off score, and parents rating their children above the cut-off score. CONCLUSIONS: This measure can be used with this group. Our group of children with severe SLI reported lower health-related quality of life than the healthy population mean as perceived by both the child and the parent. Health professionals working with children who have SLI need to consider not only a child's impairment, but also their wellbeing and participation by incorporating self- and proxy-reports into assessment in order to promote meaningful therapeutic outcomes that impact positively on a child's life. PMID- 26268358 TI - Identification and characterization of laccase-type multicopper oxidases involved in dye-decolorization by the fungus Leptosphaerulina sp. AB - BACKGROUND: Fungal laccases are multicopper oxidases (MCOs) with high biotechnological potential due to their capability to oxidize a wide range of aromatic contaminants using oxygen from the air. Albeit the numerous laccase-like genes described in ascomycete fungi, ascomycete laccases have been less thoroughly studied than white-rot basidiomycetous laccases. A variety of MCO genes has recently been discovered in plant pathogenic ascomycete fungi, however little is known about the presence and function of laccases in these fungi or their potential use as biocatalysts. We aim here to identify the laccase-type oxidoreductases that might be involved in the decolorization of dyes by Leptosphaerulina sp. and to characterize them as potential biotechnological tools. RESULTS: A Leptosphaerulina fungal strain, isolated from lignocellulosic material in Colombia, produces laccase as the main ligninolytic oxidoreductase activity during decolorization of synthetic organic dyes. Four laccase-type MCO genes were partially amplified from the genomic DNA using degenerate primers based on laccase-specific signature sequences. The phylogenetic analysis showed the clustering of Lac1, Lac4 and Lac3 with ascomycete laccases, whereas Lac2 grouped with fungal ferroxidases (together with other hypothetical laccases). Lac3, the main laccase produced by Leptosphaerulina sp. in dye decolorizing and laccase-induced cultures (according to the shotgun analysis of both secretomes) was purified and characterized in this study. It is a sensu-stricto laccase able to decolorize synthetic organic dyes with high efficiency particularly in the presence of natural mediator compounds. CONCLUSIONS: The searching for laccase type MCOs in ascomycetous families where their presence is poorly known, might provide a source of biocatalysts with potential biotechnological interest and shed light on their role in the fungus. The information provided by the use of genomic and proteomic tools must be combined with the biochemical evaluation of the enzyme to prove its catalytic activity and applicability potential. PMID- 26268359 TI - KIF5B-RET Fusion gene may coincide oncogenic mutations of EGFR or KRAS gene in lung adenocarcinomas. AB - BACKGROUND: The KIF5B-RET rearrangement is detected with the frequency of 1 ~ 2% in 'triple marker'-negative lung adenocarcinomas, i.e., EGFR, KRAS and EML4-ALK wild type. These mutational changes are known to be mutually exclusive, but the co-existence of ALK rearrangement with activating mutations of EGFR is rarely found. METHODS: We examined the KIF5B-RET fusion gene in frozen tissues from 154 surgically resected lung tumors using RT-PCR with direct sequencing and the mutation status of EGFR and KRAS genes using PNA clamping. We tested KIF5B-RET translocation in Formalin Fixed Paraffin Embedded using fluorescence in situ hybridization. We also measured RET mRNA and protein expression by RT-PCR and immunohistochemistry, respectively. RESULTS: The existence of KIF5B-RET fusion gene was identified in 9 patients. The mean age was 67.2 and M: F ratio 4:5. Of 9 patients, 3 patients harbored wild type of EGFR and KRAS gene. However, KIF5B-RET fusion gene coincided with EGFR or KRAS mutation in 6 patients. These six pts were also positive for both RET break-apart probes (23.9%) and KIF5B-RET fusion (44.4%). However, there were no correlations between RET mRNA and protein expression in the KIF5B-RET-positive patients. The median disease free survival and overall survival were 23.9 months and 29.5 months, respectively. CONCLUSIONS: Taken together, our data suggest one-step screening platform for KIF5B-RET as well as EGFR, K-RAS, ALK oncogenic mutations be necessary for lung adenocarcinoma patients because EGFR or KRAS mutation are not infrequently found in KIF5B-RET positive patients. PMID- 26268361 TI - Opinion Paper: Phytosome: A Fatty Solution for Efficient Formulation of Phytopharmaceuticals. PMID- 26268360 TI - Changes in fatty acid composition in tissue and serum of obese cats fed a high fat diet. AB - BACKGROUND: Obesity and overweight have been frequently observed in dogs and cats in recent years as in humans. The compositions of fatty acids (FAs) in the accumulated lipids in tissues of obese animals may have important roles in the process and mechanisms related to the onset of metabolic disorders. The purpose of this study was to evaluate the effects of a high fat (HF) diet, which contained a higher proportion of saturated FAs, on FA metabolism and distribution in obese cats. Cats (N = 12) were divided into control diet group (crude fat; 16.0 %) (n = 4) or a high fat (HF) diet group (crude fat; 23.9 %) (n = 8). The HF diet contained up to 60 % of calories from fat and was rich in stearic acid. Blood samples were collected at 0, 2, 4 and 6 weeks after the feeding. Adipose and liver tissues were collected at the 6(th) week after feeding. We performed analysis of histological findings and fatty acid composition in serum and tissues. RESULTS: Body weights of the cats significantly increased in the HF group. The increased activities of hepatic enzymes and the accumulation of lipid droplets were found in hepatocytes in the HF group at the 6(th) week after feeding. In this study, the stearic acid (C18:0)-rich HF diet contained less oleic acid (C18:1n-9) and more linoleic acid (C18:2n-6) than the control. However, the composition of oleic acid in the liver was higher, and those of stearic acid and linoleic acid were lower in the HF group at the 6(th) week after feeding. The higher oleic acid:stearic acid ratio suggests an increase in the conversion from saturated FA to mono-unsaturated FAs, which may reflect the hepatic storage of FAs as a relatively harmless form. CONCLUSION: The stearic acid-rich HF diet increased hepatic lipid accumulation accompanied by the increased of hepatic oleic acid, increased serum oleic acid and activation of hepatic enzymes. These findings could be an important sign of early stages of dyslipidemia and hepatic damage. Also, the higher oleic acid:stearic acid ratio might be related to the increased activity of SCD-1, which suggests that the stearic acid-rich HF diet evoked hepatic lipogenesis in the feline liver. PMID- 26268362 TI - Feasibility, Acceptability, and Preliminary Effects of the COPE Online Cognitive Behavioral Skill-Building Program on Mental Health Outcomes and Academic Performance in Freshmen College Students: A Randomized Controlled Pilot Study. AB - PROBLEM: Despite the increasing prevalence of mental health disorders in university students, few receive needed evidence-based treatment. OBJECTIVE: The purpose of this study was to assess the feasibility and preliminary effects of a seven-session online cognitive-behavioral skill-building intervention (i.e., COPE, Creating Opportunities for Personal Empowerment) versus a comparison group on their anxiety, depressive symptoms, and grade performance. METHODS: A randomized controlled pilot study was conducted from September 2012 to May 2013 with 121 college freshmen enrolled in a required one credit survey course. FINDINGS: Although there were no significant differences in anxiety and depressive symptoms between the groups, only COPE students with an elevated level of anxiety at baseline had a significant decline in symptoms. Grade point average was higher in COPE versus comparison students. Evaluations indicated that COPE was a positive experience for students. CONCLUSIONS: COPE is a promising brief intervention that can be integrated effectively into a required freshman course. PMID- 26268363 TI - Semi-automated segmentation of pre-operative low grade gliomas in magnetic resonance imaging. AB - BACKGROUND: Segmentation of pre-operative low-grade gliomas (LGGs) from magnetic resonance imaging is a crucial step for studying imaging biomarkers. However, segmentation of LGGs is particularly challenging because they rarely enhance after gadolinium administration. Like other gliomas, they have irregular tumor shape, heterogeneous composition, ill-defined tumor boundaries, and limited number of image types. To overcome these challenges we propose a semi-automated segmentation method that relies only on T2-weighted (T2W) and optionally post contrast T1-weighted (T1W) images. METHODS: First, the user draws a region-of interest (ROI) that completely encloses the tumor and some normal tissue. Second, a normal brain atlas and post-contrast T1W images are registered to T2W images. Third, the posterior probability of each pixel/voxel belonging to normal and abnormal tissues is calculated based on information derived from the atlas and ROI. Finally, geodesic active contours use the probability map of the tumor to shrink the ROI until optimal tumor boundaries are found. This method was validated against the true segmentation (TS) of 30 LGG patients for both 2D (1 slice) and 3D. The TS was obtained from manual segmentations of three experts using the Simultaneous Truth and Performance Level Estimation (STAPLE) software. Dice and Jaccard indices and other descriptive statistics were computed for the proposed method, as well as the experts' segmentation versus the TS. We also tested the method with the BraTS datasets, which supply expert segmentations. RESULTS AND DISCUSSION: For 2D segmentation vs. TS, the mean Dice index was 0.90 +/- 0.06 (standard deviation), sensitivity was 0.92, and specificity was 0.99. For 3D segmentation vs. TS, the mean Dice index was 0.89 +/- 0.06, sensitivity was 0.91, and specificity was 0.99. The automated results are comparable with the experts' manual segmentation results. CONCLUSIONS: We present an accurate, robust, efficient, and reproducible segmentation method for pre-operative LGGs. PMID- 26268364 TI - Predominance of caudate nucleus lesions in acute ischaemic stroke patients with impairment in language and speech. AB - BACKGROUND AND PURPOSE: Whereas traditional views of language processing in the brain have assumed that the language function is concentrated to a limited number of cortical areas (Broca's and Wernicke's areas), current knowledge points at a much more complex system of language and speech processing involving many brain areas, both cortical and subcortical. The purpose of the current study was to make an unbiased assessment of which cerebral areas are affected in first-ever acute ischaemic stroke patients identified as having language and speech impairments according to the National Institutes of Health Stroke Scale (NIHSS). METHODS: Data from 34 patients with language and speech impairment, with a score of 1-3 on item 9 of the NIHSS, following ischaemic stroke were collected from the Lund Stroke Register. Magnetic resonance images acquired up to 20 days after stroke onset were used to create an overlap lesion image using MRIcron software. RESULTS: The classical language areas, Wernicke's and Broca's areas, were affected in less than one-fourth of the patients. The most frequently affected region was a subcortical region--the left caudate nucleus and the adjacent corona radiata. CONCLUSIONS: These findings contribute to the growing body of evidence that the basal ganglia have a crucial role in the control over language and speech processing. PMID- 26268366 TI - Organ culture and Reflectance Confocal Microscopy as new integrated tools for barrier rescue studies in inflammatory skin diseases. PMID- 26268365 TI - A subset of patients with systemic lupus erythematosus fails to degrade DNA from multiple clinically relevant sources. AB - INTRODUCTION: Patients with systemic lupus erythematosus (SLE) have a decreased ability to clear cell remnants and multiple deficiencies in the ability to degrade cellular chromatin have been linked to the disease. Since the discovery of neutrophil extracellular traps (NETs), a renewed interest has been sparked in this field of research with multiple studies reporting a decreased ability of patients with SLE to degrade NETs. In this study we extend these findings by investigating the ability of patients with SLE to degrade chromatin from multiple clinically relevant sources. METHODS: We use flow cytometry in combination with NET degradation and DNA zymogram assays to investigate the ability of sera from SLE patients to degrade chromatin from three different sources of DNA such as NETs, apoptotic and necrotic cells. This ability was further associated with clinical manifestations. RESULTS: We found that 61% of the patients had an affected degradation of at least one chromatin source. Further, degradation of NETs correlated with degradation of chromatin from secondary necrotic cells but not with degradation of chromatin from primary necrotic cells. Patients who fail to degrade several forms of DNA more often display anti-nuclear and nephritic involvement whereas this is not observed in patients with decreased ability to degrade chromatin from primary necrotic cells. CONCLUSIONS: The majority of patients with SLE has a decreased ability to degrade chromatin from clinically relevant sources. This decreased ability is further reflected in their clinical presentation. PMID- 26268367 TI - Multimode sensors as new tools for molecular recognition of testosterone, dihydrotestosterone and estradiol in children's saliva. AB - Increased levels of testosterone (T2 ), dihydrotestosterone (DHT) and estradiol (E2 ) in children may be responsible for their early/delayed puberty and obesity conditions. Therefore, multimode sensors based on carbon matrices, such as graphite, graphene, fullerene C60 and multiwall carbon nanotubes modified with maltodextrin, were designed to assess reliably T2 , DHT and E2 in children saliva. The modes used for the assay of hormones were stochastic mode (for qualitative and quantitative determination of hormones) and differential pulse voltammetry mode (for quantitative determination of hormones). The advantage of this type of sensors, for hormone analysis, is their possibility to reach low concentration levels- are placed for children saliva under the detection limit of standard methods (e.g. ELISA used for the determination of these hormones in saliva). This made the multimode sensors an excellent tool for clinical analysis and especially for determination of substances of clinical importance in saliva samples. The proposed method is fast and simple, and no sampling of saliva is required. PMID- 26268368 TI - Very stable high molecular mass multiprotein complex with DNase and amylase activities in human milk. AB - For breastfed infants, human milk is more than a source of nutrients; it furnishes a wide array of proteins, peptides, antibodies, and other components promoting neonatal growth and protecting infants from viral and bacterial infection. It has been proposed that most biological processes are performed by protein complexes. Therefore, identification and characterization of human milk components including protein complexes is important for understanding the function of milk. Using gel filtration, we have purified a stable high molecular mass (~1000 kDa) multiprotein complex (SPC) from 15 preparations of human milk. Light scattering and gel filtration showed that the SPC was stable in the presence of high concentrations of NaCl and MgCl2 but dissociated efficiently under the conditions that destroy immunocomplexes (2 M MgCl2 , 0.5 M NaCl, and 10 mM DTT). Such a stable complex is unlikely to be a casual associate of different proteins. The relative content of the individual SPCs varied from 6% to 25% of the total milk protein. According to electrophoretic and mass spectrometry analysis, all 15 SPCs contained lactoferrin (LF) and alpha-lactalbumin as major proteins, whereas human milk albumin and beta-casein were present in moderate or minor amounts; a different content of IgGs and sIgAs was observed. All SPCs efficiently hydrolyzed Plasmid supercoiled DNA and maltoheptaose. Some freshly prepared SPC preparations contained not only intact LF but also small amounts of its fragments, which appeared in all SPCs during their prolonged storage; the fragments, similar to intact LF, possessed DNase and amylase activities. LF is found in human epithelial secretions, barrier body fluids, and in the secondary granules of leukocytes. LF is a protein of the acute phase response and nonspecific defense against different types of microbial and viral infections. Therefore, LF complexes with other proteins may be important for its functions not only in human milk. PMID- 26268369 TI - Prediction of protein-protein interaction sites from weakly homologous template structures using meta-threading and machine learning. AB - The identification of protein-protein interactions is vital for understanding protein function, elucidating interaction mechanisms, and for practical applications in drug discovery. With the exponentially growing protein sequence data, fully automated computational methods that predict interactions between proteins are becoming essential components of system-level function inference. A thorough analysis of protein complex structures demonstrated that binding site locations as well as the interfacial geometry are highly conserved across evolutionarily related proteins. Because the conformational space of protein protein interactions is highly covered by experimental structures, sensitive protein threading techniques can be used to identify suitable templates for the accurate prediction of interfacial residues. Toward this goal, we developed eFindSite(PPI) , an algorithm that uses the three-dimensional structure of a target protein, evolutionarily remotely related templates and machine learning techniques to predict binding residues. Using crystal structures, the average sensitivity (specificity) of eFindSite(PPI) in interfacial residue prediction is 0.46 (0.92). For weakly homologous protein models, these values only slightly decrease to 0.40-0.43 (0.91-0.92) demonstrating that eFindSite(PPI) performs well not only using experimental data but also tolerates structural imperfections in computer-generated structures. In addition, eFindSite(PPI) detects specific molecular interactions at the interface; for instance, it correctly predicts approximately one half of hydrogen bonds and aromatic interactions, as well as one third of salt bridges and hydrophobic contacts. Comparative benchmarks against several dimer datasets show that eFindSite(PPI) outperforms other methods for protein-binding residue prediction. It also features a carefully tuned confidence estimation system, which is particularly useful in large-scale applications using raw genomic data. eFindSite(PPI) is freely available to the academic community at http://www.brylinski.org/efindsiteppi. PMID- 26268370 TI - RACK1 (receptor for activated C-kinase 1) interactions with spectrin repeat elements. AB - Receptor for activated C-kinase 1 (RACK1) is an intracellular scaffolding protein involved in a multitude of signalling pathways. The cytoskeleton is fundamental for intracellular cell signalling as it forms an interconnected network of regulatory proteins. Here, spectrin is a central component as it forms the actin spectrin network that serves as docking surfaces for cellular components. The interaction between RACK1 and components of spectrin, the single spectrin repeats R16, R17 and the double spectrin repeat R1617 from the alpha-spectrin chain were investigated by biosensor technology and docking analysis. RACK1 associated only weakly to R16 (KD = 1.0 +/- 0.5 * 10(-6) M), about 20 times stronger to R1617 (KD = 5.3 +/- 0.7 * 10(-8) M) and 100 times stronger to R17 (KD = 0.9 +/- 0.3 * 10(-8) M). Docking analysis showed that while R16 alone preferentially docked with its B-helix, R17 docked through its A-helix and BC loop. The double repeat and RACK1 mainly formed two different complex conformations. R1617 docked tangentially to the N/C-terminal of RACK1 or radially along a groove on the outer surface of RACK1. These configurations could account for the slight increase in entropic and the decrease in enthalpic interactions for the R1617-RACK1 interaction, compared with the interactions of RACK1 to the two single repeats. Our results suggest a mode of interaction that allows spectrin to attach to the N/C part of RACK through the inter-helical AB and BC loops and adopt a multitude of configurations in between the two limiting configurations. PMID- 26268372 TI - Critical appraisal of AMSTAR: challenges, limitations, and potential solutions from the perspective of an assessor. AB - BACKGROUND: Systematic reviews are pivotal components in the development of evidence-based clinical guidelines. To evaluate the methodological quality of these systematic reviews, several tools have been proposed. Among them, the assessment of multiple systematic reviews (AMSTAR) checklist is probably used most frequently. This tool comprises 11 items related to the steps taken when conducting a systematic review, and it is claimed to have good face and content validity. The objective of this debate paper was twofold: (a) to critically evaluate the ability of all AMSTAR checklist items to adequately determine the methodological quality of a systematic review; and (b) to describe difficulties regarding interpretation of the checklist, and provide potential solutions for these difficulties. DISCUSSION: Some items of the AMSTAR checklist seem to assess the quality of reporting of a systematic review more than its methodological quality. For example, item 7 may not "capture" the true methodological quality of primary studies included in the systematic review. Item 10 does not likely result in the collection of in-depth information on the presence of publication bias in the systematic review. Furthermore, some items may be difficult to interpret, hindering accurate assessment. For example, item 5 does not explicitly indicate whether a list of documents excluded in each phase of selection (i.e., after evaluation of titles and abstracts, and after full-text assessment) should be reported. The present debate paper evaluated and discussed some methodological limitations of the AMSTAR checklist, as well as challenges involved in evaluation of the checklist's items. Several suggestions are also made to optimize the use of this checklist. The information in this paper may stimulate further discussion among systematic reviewers, methodologists and clinicians. PMID- 26268373 TI - Independent association of subclinical coronary artery disease and emphysema in HIV-infected patients. AB - OBJECTIVES: Chronic obstructive pulmonary disease (COPD) and coronary artery disease are inflammatory states with a significant clinical impact. The relationship between them has not been investigated in patients with HIV infection. We assessed the presence of subclinical emphysema and coronary artery disease using chest computed tomography (CT) imaging in a cohort of HIV-infected patients receiving antiretroviral therapy. METHODS: Gated chest CT scans were performed in 1446 consecutive patients to assess the presence and severity of coronary artery calcium (CAC) (classified as a score of 0, 1-100 or > 100) and emphysema (classified using a visual semiquantitative scale: 0, absent; 1-4, mild to moderate; > 4, severe). Univariable and multivariable logistic regression analyses were performed to identify factors independently associated with CAC and emphysema. RESULTS: The emphysema score was significantly higher in patients with CAC scores of 1-100 and > 100 compared with those with a CAC score of 0. After adjustments for age, sex, smoking status, pack-years of smoking, visceral adiposity and duration of HIV infection, the presence of any emphysema was significantly associated with a CAC score > 0 [odds ratio (OR) 1.43; 95% confidence interval (CI) 1.08-1.88; P = 0.012]. The association persisted after adjustment for the Framingham risk score (OR 1.52; 95% CI 1.16-1.99; P = 0.002). There was a dose-dependent effect in the association between emphysema score and CAC score. CONCLUSIONS: In this cross-sectional study of HIV-infected patients, there was an independent association between emphysema and CAC, after adjustment for traditional cardiovascular risk factors, suggesting a common pathogenesis of these chronic inflammatory conditions in a chronic inflammatory disease such as HIV infection. PMID- 26268374 TI - Risk factors for celiac disease. AB - Celiac Disease (CD) is an immune-mediated systemic disorder elicited by gluten and related prolamines in genetically susceptible individuals and it is the result of the interaction between genetic and environmental factors. Among genetic risk factors, the strongest association is with the HLA class II DQ region; nevertheless at least 39 non-HLA loci are associated with CD. Gluten is the main environmental trigger of the disease. In addition, infant feeding and weaning practices as well as timing of gluten introduction in the diet have been suggested to contribute to CD risk. Furthermore a role for infectious agents and microbiota composition in disease development has also been proposed.Aim of this short review is to discuss the current knowledge on both genetic and environmental risk factors for the development of CD; moreover we will provide a brief overview of the possible strategies that could be envisaged to prevent this condition, at least in the population at-risk. PMID- 26268375 TI - Effect of multifaceted interventions on reducing return visits within 72 h after non-traumatic emergency department visits. AB - OBJECTIVE: The objective of the present study is to develop new multifaceted interventions to reduce return visits (RVs) based on identified risk factors related to RVs in the ED and to compare the RV rate before and after the implementation of the intervention. METHODS: The present study was a controlled before and after study that was conducted in the ED of a 900-bed tertiary hospital in an urban area. The primary outcome was the rate of unplanned RVs to the ED and hospital admission after RV. The risk and predictive factors of RVs were identified by a retrospective study of all unscheduled RVs to the ED within 72 h in 2011. We developed five new multifaceted interventions based on the results: (i) daily RV feedback; (ii) prescription set of drugs; (iii) creation of a discharge instruction sheet; (iv) early follow-up appointments of outpatient department (OPD); and (v) enhancement of referral system. A prospective interventional study in which the interventions were implemented was then conducted over 10 months, from 1 June 2012 to 31 March 2013. RESULTS: The five new multifaceted interventions significantly reduced the mean early RV rate and RV admission rate after ED discharge by an average of approximately 25%, with a maximum of approximately 55% and 47%, respectively, compared with the pre intervention period (RV rate: P < 0.001, RV admission rate: P < 0.001). CONCLUSIONS: Multifaceted interventions based on identified risk factors for early RV after ED discharge had a positive effect on reducing RVs and the admission rate after RVs for adult patients within 72 h of non-traumatic ED visits. PMID- 26268376 TI - Polymorphisms in genes of the BAFF/APRIL system may constitute risk factors of B CLL--a preliminary study on a Polish population. AB - The association of single-nucleotide polymorphisms (SNPs) of B-cell activating factor (BAFF)/a proliferation-inducing ligand (APRIL) system with B-cell chronic lymphocytic leukemia (B-CLL) have been suggested, therefore, we investigated 20 SNPs of BAFF, APRIL, BAFF-R, transmembrane activator and calcium modulator and cyclophilin-ligand interactor (TACI), B-cell maturation antigen (BCMA) genes and the risk and outcome of B-CLL in 187 patients and 296 healthy subjects as well as ligand-receptor gene * gene interactions. Although the obtained P-values for all 20 SNPs did not reach statistical significance for this study (alpha = 0.003), the high value of the global chi-squared statistic (chi(2) df = 38 = 52.65; P = 0.0586), and obtained values of odds ratio indicate that rs9514828 (BAFF), rs3803800 (APRIL) and rs4985726 (TACI) may be associated with the risk of B-CLL. We observed that the B-CLL patients with the genotype rs9514828CT/rs11570136AA were diagnosed with the disease 12 years later than the whole group of patients in this study. PMID- 26268377 TI - The choroid and lamina cribrosa is affected in patients with Parkinson's disease: enhanced depth imaging optical coherence tomography study. AB - PURPOSE: To compare lamina cribrosa (LC) and choroidal thicknesses using enhanced depth imaging optical coherence tomography (EDI-OCT) in patients with Parkinson's disease (PD) and healthy controls. METHODS: A total number of 44 eyes of 22 patients with PD and 50 eyes of 25 healthy subjects were utilized in this institutional cross-sectional study. After a complete ophthalmic examination, all eyes were imaged with OCT (RTVue-100 version 5.1 Fourier-domain optical coherence tomography; Optovue Inc., Fremont, CA, USA); LC and choroidal thickness were assessed. RESULTS: The mean LC thicknesses were 209.4 +/- 40.2 MUm in patients with PD and 292.5 +/- 33.7 MUm in control subjects. There was a significant difference in the mean LC thickness between the groups (p < 0.0001). The choroidal thickness measurements of the PD group at the subfoveal region and 1.5 mm temporal and 1.5 mm nasal to the fovea were 228.1 +/- 44.3, 193.2 +/- 41.4 and 188.4 +/- 49.0 MUm, respectively, whereas measurements for the controls were, respectively, 246.5 +/- 38.2, 227.3 +/- 34.7 and 216.7 +/- 51.4 MUm. The choroid was significantly thinner in eyes of the PD group compared to that of the controls (p = 0.001, p < 0.001, and p = 0.006). There was no significant correlation between the disease severity and OCT parameters. The duration of the disease showed a statistically significant negative correlation with LC (rs[94] = -0.700, p < 0.001), and average subfoveal and temporal and nasal choroid thicknesses (rs[94] = -0.282, p = 0.006; rs[94] = -0.324, p = 0.001, rs[94] = 0.240, and p = 0.020, respectively). CONCLUSIONS: Regardless of the disease severity, PD may cause atrophy and volume loss in the lamina cribrosa, and choroid. An enhanced depth imaging technique may be used as an additional modality in the diagnosis and follow-up of patients with PD. PMID- 26268378 TI - Template Synthesis of Linear-Chain Nanodiamonds Inside Carbon Nanotubes from Bridgehead-Halogenated Diamantane Precursors. AB - A simple method for the synthesis of linear-chain diamond-like nanomaterials, so called diamantane polymers, is described. This synthetic approach is primarily based on a template reaction of dihalogen-substituted diamantane precursors in the hollow cavities of carbon nanotubes. Under high vacuum and in the presence of Fe nanocatalyst particles, the dehalogenated radical intermediates spontaneously form linear polymer chains within the carbon nanotubes. Transmission electron microscopy reveals the formation of well-aligned linear polymers. We expect that the present template-based approach will enable the synthesis of a diverse range of linear-chain polymers by choosing various precursor molecules. The present technique may offer a new strategy for the design and synthesis of one dimensional nanomaterials. PMID- 26268379 TI - [Aged but active people]. PMID- 26268380 TI - [Discourses about health of the aged]. PMID- 26268381 TI - [Relationship between the nutritional status and the oral function among community-dwelling dependent elderly persons]. AB - AIM: We herein examined the relationship between the nutritional status and the oral function among community-dwelling dependent elderly persons. METHODS: The subjects included 218 community-dwelling dependent elderly persons. The data were collected via questionnaires, including information regarding age, sex, the level of care required, nutritional status and swallowing function. We used the Mini Nutritional Assessment-Short Form (MNA-SF) to measure the nutritional status and the Dysphagia Risk Assessment for the Community-dwelling Elderly (DRACE) to evaluate the swallowing function. The tongue pressure and the labial closure force were measured using a tongue pressure measurement system (JMS Co. Ltd., Hiroshima, Japan) and the Lip de Cum (Cosmo-Instruments Co, Ltd, Tokyo, Japan). RESULTS: The mean MNA-SF score was 10.07+/-2.58. The mean DRACE score was 4.39+/ 3.80. The mean tongue pressure was 23.89+/-10.61 kPa. The mean labial closure force was 10.17+/-6.04 N. The results of bivariate regression analyses showed that there was a poor correlation between the MNA-SF and the DRACE, tongue pressure and labial closure force. Furthermore, the multiple regression analysis with the MNA-SF as the dependent variable revealed a correlation between the DRACE and labial closure force (p<0.01, R(2)=0.02). CONCLUSIONS: Our results suggest that the nutritional status is significantly related to the swallowing function and labial closure force among community-dwelling dependent elderly persons. PMID- 26268382 TI - [Development of a self-administered dementia checklist (SDC) (1): Examination of factorial validity and internal reliability]. AB - AIM: The aim of this study was to develop a self-administered dementia checklist (SDC), in order to help community-residing older adults realize their declining functions and encourage them to begin using necessary services, and to examine its factorial validity and internal reliability. METHODS: A panel of dementia clinical experts developed a questionnaire according to pre-selected items and conducted a self-administered survey with community-residing people aged 65 + (n=2,483). The team developed a scale through an exploratory factor analysis and item response theory (IRT) analysis (Study 1). Using this scale, they conducted a self-administered survey with community-residing people aged 65 + (n=5,199), conducted another exploratory factor analysis, and developed a 10-item scale. A confirmatory factor analysis was subsequently conducted and reliability coefficients were computed. RESULTS: The exploratory factor analysis of the proposed 37 items extracted 5 factors: Factor 1 was named "subjective decline in daily living functioning," and Factor 2 was "subjective cognitive decline" in the early stage of dementia. The team developed a 20-item scale by selecting 10 items from each factor which had high factor loadings and high slope values in the IRT analysis (Study 1). After the exploratory factor analysis of the 20-item scale, they developed a 10-item scale by selecting 5 items from each factor which had strong associations. The confirmatory factor analysis verified the 2-factor model. The Cronbach alpha coefficients for the subscales of Factors 1 and 2 were 0.935 and 0.834, respectively, and 0.908 for the overall 10-item scale. CONCLUSION: The authors developed a 10-item SDC with 2 factors and confirmed its factorial validity and internal reliability. PMID- 26268383 TI - [A study of endoscopic therapy for bile duct stones in elderly patients]. AB - AIM: To evaluate the safety and efficacy of endoscopic therapy for bile duct stones in elderly patients aged over 80 years. METHODS: We enrolled 20 elderly patients aged over 80 years and 50 patients who were younger than 79 years of age who had received their first endoscopic therapy for bile duct stones at our hospital from February 2012 to December 2013. A retrospective analysis was performed which included the following clinical parameters: the use of antithrombotic drugs; a past history of abdominal surgery; performance status (PS); the shortest diameter of the largest stone; and the total number of stones. The treatment outcomes of operations with endoscopic sphincterotomy, endoscopic papillary balloon dilation, or endoscopic papillary large balloon dilation were compared. The operative time, complete stone clearance rate, operative success rate (complete stone clearance or bile duct stent insertion), and adverse events were compared as treatment outcomes. RESULTS: There was no significant difference in the use of antithrombotic drugs, past history of abdominal surgery, number of stones, or treatment received between the age groups, while PS was significantly lower, and the diameter of the largest stone was significantly greater in the patients over 80 years of age. The operative time, complete stone clearance rate, operative success rate, and the number of adverse events did not differ significantly between the age groups. CONCLUSION: Endoscopic therapy for bile duct stones was found to be safe and effective in elderly patients over 80 years of age. PMID- 26268384 TI - [Long-term care level as a predictor of a poor outcome in elderly patients with pneumonia]. AB - AIM: To determine factors associated with physical decline and a poor prognosis after hospitalization in physically dependent elderly patients with acute pneumonia. METHODS: The subjects included 112 geriatric patients (86.8+/-5.5 years old) with acute pneumonia consecutively admitted to an inpatient unit of Geriatric Medicine, Kyorin University Hospital in the period from April 2012 to March 2013. All patients were generally treated with broad-spectrum antibiotics according to nursing- and healthcare-associated pneumonia (NHCAP) guidelines. The patients' baseline severity of pneumonia was evaluated according to the A-Drop score and their physical dependency was assessed according to the JABC score before and after admission. RESULTS: The patients were categorized into the community acquired pneumonia group (CAP) (n=29) and NHCAP group (n=83). The patients in the NHCAP group had a longer hospital stay (NHCAP vs. CAP: 33 vs. 21 days, p=0.02), higher A-Drop scores (2.88+/-0.80 vs. 2.45+/-0.87 points, p=0.02) and were more frequently diagnosed with aspiration pneumonia (89.2% vs. 42.9%, p<0.0001) than those in the CAP group. Three patients in the CAP group (10.3%) and 13 patients in the NHCAP group (15.7%) died during their hospital stay (p=0.69). Although the rest of the patients were successfully treated for pneumonia, their physical dependency progressed after admission in both groups (p<0.0001). After adjusting for age, gender and the JABC score before admission, NHCAP (risk ratio against CAP: 6.2, 95% CI 1.2-32.2, p=0.03) and a serum albumin lower than 2.5 g/dl (RR: 7.8, 95%CI 1.7-35.7, p<0.01) were significantly associated with the progression of physical dependency after admission. CONCLUSIONS: The diagnosis of NHCAP is a risk factor for the progression of physical dependency. Therefore, palliative care may be an optional approach for frail patients. PMID- 26268385 TI - [Cross-sectional and longitudinal associations of physical performance and skeletal muscle mass with cognition and cognitive decline among community dwelling older Japanese]. AB - AIM: This study had two objectives: to confirm the cross-sectional associations between the physical performance scale (PPS), skeletal muscle mass (SMM) and sarcopenia and cognition, and to examine whether PPS, SMM and sarcopenia are independent risk markers of cognitive decline (CD). METHODS: Among 805 adults 65 years of age or older who participated in a baseline survey (2008-2011), 649 were reevaluated for their level of cognition at least once until 2012, and PPS, SMM, sarcopenia and cognition were assessed. CD was defined as a decrease of at least 0.5 points per year on the MMSE. RESULTS: After controlling for sex, age and years of education, PPS, SMM and sarcopenia were associated with cognition, respectively. During a median follow-up of 3.0 years, 201 adults (31.0%) had CD. After controlling for important confounders, PPS showed a significant association with CD [OR=0.75 (95%CI: 0.65-0.87)], whereas SMM showed no significant association with CD. As compared with the people who had normal PPS and SMM, people who had low PPS and normal SMM had 2.10 times higher risk for CD. CONCLUSIONS: We confirmed the cross-sectional associations between physical performance, SMM and sarcopenia and cognition in a general population of older adults. Although people had normal SMM, low physical performance was found to be a risk marker for subsequent CD. PMID- 26268386 TI - [A case of acute respiratory failure in an elderly patient with elderly asthma COPD overlap syndrome (ACOS) is differentiated from acute eosinophilic pneumonia]. AB - We report a case of acute respiratory failure in a 77-year-old male with chronic obstructive pulmonary disease (COPD) who showed marked eosinophilia (61.5% of the peripheral total white blood cells [WBCs]; 13,200/mm(3)). The patient was an ex smoker, but he had started smoking again one month previously, His forced expiratory volume in one second (FEV1) was low and dyspnea symptom was observed. Although rhonchi were detected, wheezing chest sounds were not detected. Chest X radiography and computed tomography of the lung revealed diffuse bilateral pulmonary infiltrates and emphysematous changes. He was given intravenous methyl prednisolone (1,000 mg) for 3 consecutive days. The abnormal shadows on the chest X-ray film improved remarkably and the eosinophils in his peripheral blood were reduced. Furthermore, it was no longer necessary to administer oxygen to treat his hypoxemia. The symptomatic and clinical course mimicked to a case of acute eosinophilic pneumonia (AEP). However, transbronchial lung biopsy specimens did not reveal eosinophilic infiltration in the alveolar septa. The fraction of eosinophils in the patient's bronchoalveolar lavage was 4.4% and not greater than 25%. After hospitalization, 5-15 mg of prednisolone administered orally in combination with bronchodilators to better manage his clinical symptoms. This case was thus determined to correspond to elderly asthma-COPD overlap syndrome (ACOS). PMID- 26268387 TI - [Elderly patient with acquired hemophilia A with IX?XI and XII factor decline]. AB - Acquired hemophilia is a rare bleeding diathesis caused by autoantibodies against clotting factor VIII. Many cases are associated with autoimmune disease, malignancy and an elderly status. Acquired hemophilia is very rare, with a reported annual incidence of 1.48/million/y. However, it is necessary to consider this rare disease when encountering bleeding of unknown cause in elderly patients. An 84-year-old woman was referred to our hospital with subcutaneous bleeding and anemia. The patient had severe anemia and a prolonged activated partial prothrombin time (APTT). Despite the administration of red blood cell transfusions, the decline in hemoglobin continued. Since the activity of coagulation factor VIII was <1%, and the level of inhibitor against coagulation factor VIII (509 BU/ml) was >5 BU/ml, the patient was diagnosed with acquired hemophilia. No underlying diseases were found, and we concluded that this case was idiopathic. Although she was treated with prednisolone at a dose of 40 mg per day, the bleeding tendency did not improve. Therefore, she was given activated prothrombin complex concentrates (APCC) for four days. The subcutaneous bleeding and Hb decline stopped, and the dose of prednisolone was gradually reduced. The patient's clotting function and clinical course were satisfactory, and she was discharged on the 64th day. An early diagnosis and optimal treatment are critical for treating acquired hemophilia. The development of a bleeding tendency related to the appearance of coagulation factor VIII inhibitor is serious in many patients. Therefore, recognizing this disease and providing prompt management are necessary. PMID- 26268388 TI - [Results of a survey on lectures on geriatrics--a survey among students attending a course on work therapy]. PMID- 26268389 TI - [Geriatric medicine at Kyorin University Medical School]. PMID- 26268395 TI - Enhanced active motion of Janus colloids at the water surface. AB - We have investigated the active motion of self-propelled colloids confined at the air-water interface and explored the possibility of enhancing the directional motion of self-propelled Janus colloids by slowing down their rotational diffusion. The two dimensional motion of micron-sized silica-platinum Janus colloids has been experimentally measured by particle tracking video-microscopy at increasing concentrations of the catalytic fuel, i.e. H2O2. Compared to the motion in the bulk, a dramatic enhancement of both the persistence length of trajectories and the speed has been observed. The interplay of colloid self propulsion, due to an asymmetric catalytic reaction occurring on the colloid, surface properties and interfacial frictions controls the enhancement of the directional movement. The slowing down of the rotational diffusion at the interface, also measured experimentally, plays a pivotal role in the control and enhancement of active motion. PMID- 26268394 TI - Willingness to receive text message medication reminders among patients on antiretroviral treatment in North West Ethiopia: A cross-sectional study. AB - BACKGROUND: Non-adherence to Antiretroviral Treatment (ART) is strongly associated with virologic rebound and drug resistance. Studies have shown that the most frequently mentioned reason for missing ART doses is the forgetfulness of patients to take their medications on time. Therefore using communication devices as reminder tools, for example alarms, pagers, text messages and telephone calls could improve adherence to ART. The aim of this study is to measure access to cellphones, willingness to receive text message medication reminders and to identify associated factors of ART patients at the University of Gondar Hospital, in North West Ethiopia. METHODS: An institution based cross sectional quantitative study was conducted among 423 patients on ART during April 2014. Data were collected using structured interviewer-administered questionnaires. Data entry and analysis were done using Epi-Info version 7 and SPSS version 20 respectively. Descriptive statistics and multivariable logistic regression analysis were used to describe the characteristic of the sample and identify factors associated with the willingness to receive text message medication reminders. RESULTS: A total of 415 (98% response rate) respondents participated in the interview. The majority of respondents 316 (76.1%) owned a cellphone, and 161(50.9%) were willing to receive text message medication reminders. Positively associated factors to the willingness were the following: Younger age group (AOR = 5.18, 95% CI: [1.69, 15.94]), having secondary or higher education (AOR = 4.61, 95% CI: [1.33, 16.01]), using internet (AOR = 3.94, 95% CI: [1.67, 9.31]), not disclosing HIV status to anyone other than HCP (Health Care Provider) (AOR = 3.03, 95% CI: [1.20, 7.61]), availability of radio in dwelling (AOR = 2.74 95% CI: [1.27, 5.88]), not answering unknown calls (AOR = 2.67, 95% CI: [1.34, 5.32]), use of cellphone alarm as medication reminder (AOR = 2.22, 95%CI [1.09, 4.52]), and forgetting to take medications (AOR = 2.13, 95% CI: [1.14, 3.96]). CONCLUSIONS: A high proportion of respondents have a cell phone and are willing to use it as medication reminders. Age, educational status and using internet were the main factors that are significantly associated with the willingness of patients to receive text message medication reminders. PMID- 26268396 TI - Subcutaneous porocarcinoma clinically presenting as a soft tissue tumor. AB - Porocarcinoma is a rare malignancy with glandular adnexal differentiation. A 38 year-old Japanese man noticed a subcutaneous mass in right inguinal region about 20 years prior to being examined. Radiological examinations demonstrated the mass, 11 * 10 cm in size, was in the subcutaneous fat tissue. Recently, the mass grew rapidly, and it was biopsied by an orthopedist based on clinical diagnosis of primary soft tissue tumor. Histopathological examination of the resected specimens also revealed that the tumor lacked involvement to the skin. Microscopically, the tumor was mainly composed of poroid cells with partially obvious squamous differentiation, accompanied by focal ductal structures immunoreactive for CEA and EMA. The tumor contained a low-grade area consisting of poroid cells and high-grade area with squamous differentiation. This histopathological heterogeneity suggested malignant transformation from poroma. The patient had the tumor in almost same size over the period of 20 years, which is the longest in the previous reports. This unique case of subcutaneous porocarcinoma is reported. PMID- 26268397 TI - Low-dosed docetaxel showed equivalent efficacy but improved tolerability compared with oxaliplatin in the S-1-based first-line chemotherapy regimen for metastatic or recurrent gastric adenocarcinoma. AB - Platinum-fluoropyrimidine combinations are the preferred first-line options for advanced gastric cancer (AGC) in East Asia. On the other hand, docetaxel containing regimens without platinum have demonstrated promising activity in AGC. However, dose-related toxicity of docetaxel has limited its clinical adoption. This study compared the efficacy and safety of a modified low-dosed docetaxel plus S-1 (mDS) with oxaliplatin plus S-1 (SOX) in Chinese patients with AGC. Patients were assigned to receive either oxaliplatin (100 mg/m(2)) in the SOX arm or docetaxel (40 mg/m(2)) in the mDS arm on day 1 of every 3-week cycle. S-1 80 120 mg/day was administered orally on days 1-14 in the 3-week cycle in both groups. One hundred and eighty-eight patients (mDS regimen 101; SOX 87) showed similar overall survival (OS; 13.1 vs 12.8 months, P = 0.878), progression-free survival (PFS; 5.8 vs 5.5 months, P = 0.924), and overall response rate (39.7 vs 44.2%, P = 0.569) in the mDS and SOX arms, respectively. mDS was associated with significantly less grade 3/4 toxicities in thrombocytopenia (5.9 vs 16.1%) and gastrointestinal disturbances (1.0 vs 8.0%). Furthermore, in patients who had ever received oxaliplatin-based adjuvant chemotherapy (N = 40), mDS resulted in significantly superior OS (17.8 vs 9.5 months, P = 0.015) and PFS (7.0 vs 4.2 months, P = 0.008) compared with SOX. In conclusion, mDS was as effective as SOX in Chinese patients with AGC, but it resulted in a significantly improved tolerability. In patients who received oxaliplatin-based adjuvant chemotherapy before, mDS was associated with improved efficacy in the first-line setting. PMID- 26268398 TI - The relationship between mean arterial pressure and decreased glomerular filtration rate in rural areas of Northeast China. AB - BACKGROUND: Low mean arterial pressure (MAP) can cause low renal blood flow and damage the kidneys. However, in the general population, it remains unclear whether or not decline in renal function is related to MAP. The present study examined the relationship between MAP and decreased glomerular filtration rate(GFR) in participants aged >= 35 years from the Liaoning province of China. METHODS: A total of 11345 representative individuals aged >= 5 years was selected and a cross-sectional survey was conducted from January 2012 to August 2013 to describe the gender-specific prevalence and factors associated with decreased GFR in rural areas of Liaoning Province. RESULTS: Men with decreased eGFR (eGFR < 60 ml/min per 1.73 m(2)) were older, and had higher meanWC, systolic and diastolic BP, PP, MAP, total fasting glucose, LDL-C ,glyceride and uric acid levels and were current drinker/smoker at the baseline (all P < 0.05). Those with low education level, low income, low physical activity, low hemoglobin and HDL-C level had decreased eGFR (all P < 0.05). In women, the results were similar to those of men, but DBP and drinking status had no associations with the eGFR at the baseline (all P < 0.05). After adjustment for age, men with MAP of > 112.2 mmHg versus <= 93.8 mmHg had ORs for decreased eGFR of 2.367 (95 % CI: 1.248 to 4.488) .After multivariable adjustment, an MAP of > 112.2 mmHg versus <= 93.8 mmHg had an OR for decreased eGFR of 3.249 (95 % CI:1.394 to 7.575) in men, whereas in women, MAP was not associated with decreased eGFR. CONCLUSIONS: MAP was associated with decreased eGFR in men, while in women MAP was not associated with decreased eGFR. These findings provide some evidence that a different adaptive response to renal regulation may exist in males and females. PMID- 26268399 TI - Study of Pathogens of Fungal Keratitis and the Sensitivity of Pathogenic Fungi to Therapeutic Agents with the Disk Diffusion Method. AB - PURPOSE/AIM OF THE STUDY: To identify the causative fungi of fungal keratitis, test their susceptibility to antifungal agents with the disk diffusion method and study the relationship between the organisms, the inhibition zones and the clinical outcomes. MATERIALS AND METHODS: 535 patients with fungal keratitis in one eye were included in this study. Pathogenic fungi were isolated by corneal scraping, identified by fungal cultivation and subjected to drug sensitivity tests conducted with the disk diffusion method. The patients were treated initially with voriconazole, terbinafine and natamycin eye drops for one week. Further treatment continued using the most effective drug according to the drug sensitivity results. The patients were followed up every week until three months after cured. The inhibition zones of fungi cultured with voriconazole, terbinafine and natamycin were compared. The relationship between inhibition zones and organism, organism and treatment results measure, and each treatment results measure and inhibition zones were evaluated. RESULTS: Of 535 patients, 53.84%, 19.25% and 26.91% were infected with Aspergillus, Fusarium and other fungi, respectively. Keratitis patients infected with Aspergillus keratitis had the worst outcome. The size of the inhibition zones of Aspergillus spp., Fusarium spp. and other fungal genera differed significantly in response to voriconazole, terbinafine and natamycin. The inhibition zone associated with natamycin correlated significantly with the clinical outcome of fungal keratitis (OR = 0.925), but no other such correlations were found for the other drugs tested. CONCLUSIONS: Aspergillus and Fusarium were the predominant pathogenic genera causing fungal keratitis in our patients. Among the causative fungi, infections due to Aspergillus spp. were associated with the worst outcomes. The inhibition zones of fungal isolates in response to natamycin significantly correlated with the treatment outcomes of keratitis. Specifically, the smaller the natamycin inhibition zone, the lower the probability that the fungal keratitis had been eliminated. PMID- 26268400 TI - Co-expression of tonoplast Cation/H(+) antiporter and H(+)-pyrophosphatase from xerophyte Zygophyllum xanthoxylum improves alfalfa plant growth under salinity, drought and field conditions. AB - Salinity and drought are major environmental factors limiting the growth and productivity of alfalfa worldwide as this economically important legume forage is sensitive to these kinds of abiotic stress. In this study, transgenic alfalfa lines expressing both tonoplast NXH and H(+)-PPase genes, ZxNHX and ZxVP1-1 from the xerophyte Zygophyllum xanthoxylum L., were produced via Agrobacterium tumefaciens-mediated transformation. Compared with wild-type (WT) plants, transgenic alfalfa plants co-expressing ZxNHX and ZxVP1-1 grew better with greater plant height and dry mass under normal or stress conditions (NaCl or water-deficit) in the greenhouse. The growth performance of transgenic alfalfa plants was associated with more Na(+), K(+) and Ca(2+) accumulation in leaves and roots, as a result of co-expression of ZxNHX and ZxVP1-1. Cation accumulation contributed to maintaining intracellular ions homoeostasis and osmoregulation of plants and thus conferred higher leaf relative water content and greater photosynthesis capacity in transgenic plants compared to WT when subjected to NaCl or water-deficit stress. Furthermore, the transgenic alfalfa co-expressing ZxNHX and ZxVP1-1 also grew faster than WT plants under field conditions, and most importantly, exhibited enhanced photosynthesis capacity by maintaining higher net photosynthetic rate, stomatal conductance, and water-use efficiency than WT plants. Our results indicate that co-expression of tonoplast NHX and H(+) PPase genes from a xerophyte significantly improved the growth of alfalfa, and enhanced its tolerance to high salinity and drought. This study laid a solid basis for reclaiming and restoring saline and arid marginal lands as well as improving forage yield in northern China. PMID- 26268401 TI - Does optimal lesion preparation reduce the amount of acute recoil of the Absorbe BVS? Insights from a real-world population. AB - OBJECTIVES: To evaluate the acute recoil of the ABSORB bioabsorbable vascular scaffold (BVS) and its relationship with procedural characteristics in a real world population. BACKGROUND: In vivo acute recoil of the BVS was evaluated in selected patients. METHODS: Acute recoil was studied with videodensitometry in a consecutive series of patients treated by means of a BVS, and the results were compared with those obtained in subjects receiving an everolimus-eluting stent (EES). Recoil was defined as the difference between the mean diameter of the fully expanded balloon on which the device was mounted (or the mean diameter of the post-dilatation balloon), and the mean luminal diameter of the treated segment immediately after the final inflation. RESULTS: Recoil was assessed in 106 lesions treated with a BVS and 71 treated with an EES. The absolute and percent recoil of the BVS were significantly greater (0.32 +/- 0.16 mm and 10% +/ 5% vs. 0.17 +/- 0.07 and 5% +/- 3%; P < 0.001). Multiple regression analysis showed that BVS use was associated with acute recoil (beta = 0.477; P<0.001). Suboptimal lesion preparation (residual stenosis after balloon angioplasty >20%) (beta = 0.217; P = 0.027) and a small vessel reference diameter (beta = 0.335; P = 0.002) were associated with increased BVS but not EES recoil. CONCLUSIONS: In unselected patients, the acute recoil of the BVS was significantly greater than that of the metal EES. In the BVS group, residual stenosis after predilatation correlated with percent recoil, and so optimal lesion preparation seems to be mandatory in order to maximize the mechanical properties of the scaffold. PMID- 26268404 TI - [Guideline for the diagnosis and treatment of endometriosis]. PMID- 26268402 TI - Impairment of dendritic cell function and induction of CD4(+)CD25(+)Foxp3(+) T cells by excretory-secretory products: a potential mechanism of immune evasion adopted by Echinococcus granulosus. AB - BACKGROUND: Cystic echinococcosis, caused by infection with Echinococcus granulosus, is one of the most widespread zoonotic helminth diseases. Modulation of host responses is an important strategy used by helminth parasites to promote infection. To better understand the mechanisms adopted by E. granulosus to escape host immune responses, we investigated the effects of excretory-secretory products (ES) and adult worm antigen (AWA) derived from adult E. granulosus on murine bone marrow-derived dendritic cells (BMDC). RESULTS: Compared with lipopolysaccharide (LPS), AWA, but not ES, induced BMDC maturation or stimulated BMDC cytokine production and co-stimulatory molecule expression (CD40, CD80 and MHC class II). Furthermore, ES-treated BMDCs pulsed with ovalbumin exhibited reduced co-stimulatory molecule expression in comparison with untreated BMDC, even in the presence of the strong Th1 inducer, CpG. Moreover, we detected the effects of ES-treated DC on T cell activation by an in vitro T cell priming assay. We observed that ES-treated BMDC co-cultured with DO11.10 transgenic CD4(+) T cells induced the generation of CD4(+)CD25(+)Foxp3(+) T cells. In addition, in contrast to AWA-treated BMDCs, which had markedly induced IFN-gamma secretion and reduced of IL-4 levels in co-cultured T cells, ES-treated BMDCs did not modify their capacity to stimulate IFN-gamma or IL-4 production by T cells. CONCLUSIONS: We conclude that ES of adult E. granulosus inhibited DC function, impaired the development of Th1 cells induced by CpG, and induced CD4(+)CD25(+)Foxp3(+) regulatory T cells in an IL-10-independent manner. PMID- 26268405 TI - [Variation of prevalence of macrosomia and cesarean section and its influencing factors]. AB - OBJECTIVE: To investigate the varaiation of the incidence of macrosomia and its influencing factors. METHODS: A population-based study of 25 944 pregnant women, who delivered in Peking University First Hospital in term birth, with singleton, between Jan. 1, 2006 and Dec. 31, 2013 and accepted the gestational diabetes mellitus (GDM) screening and diagnosis, was performed. The women are grouped according to the different clinical interventions at different period. Women delivered between Jan.1, 2006 and Dec. 31, 2006 was defined as Group 2006, and they were diagnosed with glucose metabolism disorder [gestational impaired glucose tolerance (GIGT) and GDM] and intervened only when meeting National diabetes data group (NDDG) criteria. Women delivered between Jan. 1, 2007 and Apr. 30, 2011 were defined as Group post 2007, and NDDG criteria was also applied in this period. Women delivered between May. 1, 2011 and Dec. 31, 2013 were defined as Group post 2011, and Ministry of Health (MOH) of China was used for GDM diagnosis in this group. All pregnant women in Group post 2007 accepted the preliminary pregnancy nutrition advice and weight management. All participants met MOH criteria were diagnosed as glucose metabolism disorder in this study, in which women diagnosed and intervened in pregnancy were defined as Group diagnosis and those not being identified during pregnancy were defined as Group missed diagnosis. It was analyzed retrospectively for the incidence of macrosomia and the influencing factor. RESULTS: (1) The prevalence of macrosomia and cesarean section was decreased every year from Jan. 2006 to Dec. 2013. The incidence of macrosomia was 9.14% in 2006, reduced to 8.02% in 2007-2011 and 6.79% in 2011 2013. The incidence of cesarean section was 55.22%, reduced to 51.04% in 2007 2011 and 44.15% in 2011-2013. However, there was not remarkable change in the prevalence of small for gestational age (P > 0.05). (2) Compared with Group 2006, the incidence of cesarean section was lower in Group post 2007 [51.04% (6 504/12 744) vs 55.22% (1 371/2 483)], and the difference is significantly (P < 0.05). Meanwhile, the incidence of cesarean section (44.15%, 4 732/10 717) and macrosomia (6.79%,728/10 717) in Group post 2011 was lower significantly than Group 2006 and Group post 2007 (P < 0.05). (3) The incidence of macrosomia was 7.41% (1 129/15 227) and 6.61% (1 006/15 227) respectively in Group diagnosis and Group missed diagnosis before May 2011, combined 14.02% (2 135/15 227) in total. It was increased significantly in the incidence of GDM 21.41% (2 294/10 717) after May 2011 compared with that before (P < 0.05). The incidence of macrosomia was decreased significantly using MOH criteria in GDM women since 2011. It was the downtrend in the incidence of macrosomia since 2007 in non GDM women. However, there was no difference in SGA in different period. (4) In glucose metabolism disorder women, compared with Group 2006 and Group post 2007, the incidence of macrosomia and cesarean section was lower in Group post 2011, and the difference is significantly (P < 0.05). However, there was no significant difference in the incidence of macrosomia and cesarean section between Group 2006 and Group post 2007, and there was no difference in SGA in the 3 groups ( P > 0.05). In non GDM women, the incidence of macrosomia and cesarean section was lower in Group post 2011 than Group 2006 (P < 0.05); meanwhile, it was the downtrend in the incidence of macrosomia in Group post 2007 compared to Group 2006, and the difference of the incidence of cesarean section was significant (P < 0.05). CONCLUSION: The prevalence of macrosomia and cesarean section might be reduced by application of suitable criteria for diagnosis of GDM and education on nutrition during pregnancy. PMID- 26268407 TI - [Effect of S100 calcium binding protein A12 on the pathogenesis of preeclampsia]. AB - OBJECTIVE: To investigate the role of S100 calcium binding protein A12 (S100A12) in the pathogenesis of preeclampsia. METHODS: Sixty patients with preeclampsia were recruited from March 2013 to December 2013 in the First Affiliated Hospital of Zhengzhou University. Among them, thirty cases were defined as the mild preeclampsia group and thirty cases were defined as the severe preeclampsia group. The other thirty healthy pregnant women were recruited in the healthy pregnant women group. The levels of S100A12 protein in maternal peripheral blood were detected by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry of streptavidin peroxidase biotin (SP) method was used to measure the protein expression of S100A12. The trophoblast cells were cultured in vitro with plasma from the three groups, and a blank control group was set up as well. Transwell was used to detect the cytotrophoblast invasion ability. Western blot was used to measure the protein expression level of receptor for advanced glycation end products (RAGE). RESULTS: (1) The levels of S100A12 in maternal peripheral blood of patients with preeclampisa [mild group: (30.8+/-2.7) ug/L, severe group: (49.3+/-4.1) ug/L] were significantly higher than that of the control group [(15.8+/-1.4) ug/L]. In addition, compared with the mild preeclampsia group, the level of S100A12 in the severe preeclampsia group was significantly higher (P < 0.05). (2) Positive immunostaining of S100A12 was observed in the cytoplasm of cytotrophoblast, decidual cells and the placentas from the three groups. The positive rate in the mild preeclampisa group was 77% (23/30); in the severe preeclampsia group it was 93% (28/30); and in the healthy pregnant women group it was 23% (7/30). The positive rates of placenta in the mild and severe preeclampsia groups were significantly higher than that in the healthy pregnant women group (P < 0.05). In addition, compared with the mild preeclampsia group, the positive rate of immunostaining of S100A12 in the severe group was significantly higher (P < 0.05). (3) Cytotrophoblast invasion ability and the expression of RAGE in the mild preeclampsia group were 29.1+/-3.2 and 0.479+/ 0.038, respectively; in the severe preeclampsia group they were 16.8+/-2.5 and 0.652+/-0.059; in the healthy pregnant women group they were 38.6+/-24.3 and 0.327+/-0.024; and in the blank control group they were 42.6+/-5.6 and 0.194+/ 0.011. Cytotrophoblast invasion ability and the expression of RAGE protein in the mild and severe preeclampsia groups were significantly higher than those in the healthy pregnant women group and the control group(P < 0.05). CONCLUSIONS: The expression of S100A12 increased in materal peripheral blood and placenta, and the receptor protein of S100A12 RAGE also had high expression. It suggested that the S100A12 may have some effect on the pathogenesis of preeclampsia. PMID- 26268406 TI - [Analysis of emergency obstetric hysterectomy: the change of indications and the application of intraoperative interventions]. AB - OBJECTIVE: To investigate the change of indications of emergency obstetric hysterectomy and the clinical application of intraoperative interventions. And to provide evidence for prevention of hysterectomy and improvement of obstetric quality. METHODS: Clinical data were collected from 97 patients who received emergency obstetric hysterectomy at Shengjing Hospital of China Medical University between January 1st, 2004 and December 31st, 2013. The patients were divided into two groups by the time point of January 1st, 2009: the first group was cases treated between January 1st, 2004 and December 31st, 2008, while the second group was cases treated between January 1st, 2009 and December 31st, 2013. The clinical indicators, surgical indications, intraoperative interventions, and blood loss between the two groups were analyzed retrospectively. RESULTS: (1) Incidence: 54 857 women delivered at Shengjing Hospital of China Medical University between January 1st, 2004 and December 31st, 2013. Of them, 97 patients received emergency obstetric hysterectomy, with an incidence of 0.177% (97/54 857). (2) The 17 patients delivered vaginally (18%,17/97) and 80 by caesarean section (83%,80/97). Forty-nine patients experienced repregnancy with scar uterus (51% , 49/97). About 41 patients underwent abdominal total hysterectomy (42%,41/97) and 56 received subtotal hysterectomy (58%, 56/97). (3) The number of patients were comparable between the two groups (50 vs 47; P > 0.05). (4) The main surgical indication was uterine inertia (45%, 44/97). The main causes of uterine inertia were excessive uterine tension (45%, 20/44) and placental abruption due to gestational hypertension (32%, 14/44). Of all the indications, 29 patients in the first group (58%, 29/50) and 15 patients in the second group (32%, 15/47) suffered from postpartum hemorrhage. Pathological placenta embedment occurred in 15 patients in the first group (30%, 15/50) and 25 patients in the second group (53%, 25/47). The incidences of postpartum hemorrhage due to uterine inertia or pathological placenta embedment were significantly different between the two groups (both P < 0.05), respectively. (5) In the first group, the average preoperative blood loss was (2 900+/-1 900) ml, and the average intraoperative amount of infused white & red blood cells was (5.9+/-3.5) U, with the average operation time of (2.2+/-1.8) hours and the average in-hospital duration of (7.8+/-2.3) days. In the second group, the average preoperative blood loss was (3 100+/- 2 200) ml, and the intraoperative amount of infused white & red blood cells was (6.2+/-5.2) U, with the average operation time of (2.5+/-2.1) hours and the average in-hospital duration of (7.9+/-2.9) days. There was no significant difference between the two groups in any of these indicators (P > 0.05). Postpartum hemorrhage was usually treated with uterine packing in the first group, but was preferentially treated with potent uterine contraction agents, arterial ligation, uterine balloon compression or B-Lynch suture in the second group. The therapeutic effects of these new treatments were significantly better than uterine packing (P < 0.05). CONCLUSIONS: The incidence of emergency obstetric hysterectomy did not change significantly in the past decade. However, the indications and intraoperative interventions have changed significantly in the second five years compared with the first five years. The main surgical indications were uterine inertia and postpartum hemorrhage due to pathological placenta embedment. Therefore, strict control of caesarean section indications was important to reduce emergency obstetric hysterectomy. PMID- 26268408 TI - [Randomized, blind, parallel-controlled and multiple-centre clinical trial on the effectiveness and safety of leuprolide acetate in the treatment of endometriosis]. AB - OBJECTIVE: To evaluate the effectiveness and safety of leuprolide acetate in the treatment of endometriosis. METHODS: From Nov. 2007 to Oct. 2012, the patients who confirmed to be endometriosis were randomly divided into test group of 113 cases and control group of 116 cases. The test drug was the sustained-release agent of leuprolide acetate. The control drug was Enantone. The drugs were used for 3 times in total. After treatment, the ovarian mass volumes measured with type-B ultrasound, the scores of the patient's subjective symptoms during non menstrual and menstruation days, the pelvic signs during non-menstrual days, the changes of hormones [estradiol (E2), FSH, LH], and adverse events were observed. RESULTS: After the treatment, the rate of changes of ovarian mass volume (among them, at 12 weeks after the first injection, the median was -55.83% in the test group, -68.22% in the control group, P = 0.336), the distinct improvement rate of symptom scores and pelvic signs during non-menstrual days [among them, at 12 weeks after the first injection, the rate of lower abdomen pain was 47.5% (48/101) in the test group, 44.0% (44/100) in the control group, P = 0.881], the hormone (E2, FSH, LH) levels [among them, at 12 weeks after the first injection, the serum level of E2, was (33+/-38) pmol/L in the test group, (38+/-40) pmol/L in the control group, P = 0.414; the serum level of FSH, was (5.1+/-2.8) U/L in the test group, (5.3+/-2.3) U/L in the control group, P = 0.666; the serum level of LH, was (0.6+/-0.8) U/L in the test group, (0.6+/-0.9) U/L in the control group, P = 0.907], had no statistically significant difference between the two groups (all P > 0.05). The distinct improvement rate and improvement rate of symptom (lower abdomen pain, low back pain) scores during menstruation days at 12 weeks after the first injection, the rates of lower abdomen pain were 73.9% (34/46), 15.2% (7/46) respectively in the test group, 72.3% (34/47), 2.1% (1/47) respectively in the control group, had statistically significant difference between the two groups (P = 0.026). There was no serious adverse event occurred in both two groups. The incidence rate of adverse event was 33.6% (38/113) in test group, 23.2% (27/116) in control group, there was no significant difference between the two groups (P = 0.082). CONCLUSION: Leuprolide acetate is effective and safe in the treatment of endometriosis. PMID- 26268409 TI - [Association of the H770H of PR gene polymorphism with susceptibility to endometriosis]. AB - OBJECTIVE: To investigate the association of PR gene exon 5 region H770H (rs1042839) single nucleotide polymorphism (SNP) with the genetic susceptibility to endometriosis (EM) in southern Han Chinese women. METHODS: Totally 431 EM patients and 499 non-EM women were collected and separated into EM group and control group, that all cases were confirmed by operation and pathology. A case control study was performed in EM and control groups to evaluate the association of these SNP with the susceptibility to EM by using a fluorescent quantitative PCR-based high resolution melting (HRM) method. RESULTS: The C and T of PR H770H allele frequencies among the EM and control groups were 97.9% (844/862), 2.1% (18/862) and 99.4% (992/998), 0.6% (6/998), respectively. The CC, CT and TT of PR H770H genotype frequencies among the EM and control groups were 95.8% (413/431), 4.2% (18/431), 0 and 98.8% (493/499), 1.2% (6/499), 0, respectively. There were statistical significances in the PR H770H alleles and genotypes distributions between the two groups (chi(2)=7.386, P=0.007; chi(2)=8.135, P=0.004). Carrying allele C reduced the risk of EM (OR=0.986, 95%CI: 0.976-0.996), while carrying allele T enhanced the risk of EM (OR=3.319, 95% CI: 1.323-8.325); carrying genotype CC reduced the risk of EM 0.970 time (OR=0.970, 95% CI: 0.949-0.991), whereas carrying genotype CT enhanced the risk of EM 3.473 times (OR=3.473, 95%CI: 1.391-8.671). CONCLUSION: There is significant association between the polymorphism of PR H770H and genetic susceptibility to EM in southern Han Chinese women. PMID- 26268410 TI - [Clinical analysis of 32 cases with neuroendocrine carcinoma of the uterine cervix in early-stage disease]. AB - OBJECTIVE: To investigate the survival and recurrence data after treatment in neuroendocrine carcinoma of the uterine cervix (NECUC) with stage Ib-IIa, and to analyse its prognostic factors. METHODS: Thirty-two cases of primary NECUC in early-stage disease treated from Jan. 2005 to Dec. 2013 at Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences were reviewed, and their data of clinicopathologic characteristics were collected and analysed. The median age was 37 years (range, 23-57 years). The distribution by International Federation of Gynecology and Obstetrics (FIGO) clinical stage: 19 cases stage Ib1, 10 cases stage Ib2, 1 case stage IIa1, 2 cases stage IIa2. Pathologic types: 22 cases of small cell carcinoma, 1 case of atypical carcinoid, 9 cases of mixed carcinoma. The diameter of cervical tumor: 12 cases >=4 cm, 20 cases <4 cm. All patients underwent radical hysterectomy and pelvic +/- para aortic lymphadenectomy, and 15 cases of them were preserved unilateral or bilateral ovaries. Pathologic examination showed that 25 cases with cervical deep stromal invasion thickness >=1/2, 21 cases with lymph-vascular space invasion (LVSI), and 18 cases with pelvic and (or) para-aortic lymph nodes involvement. Ten cases were performed neoadjuvant chemotherapy (range,1-3 cycles), all patients received postoperative chemotherapy (range,3-6 cycles), and 15 patients were treated with radiotherapy after surgery. The follow-up data were updated on Jul. 2014. The median follow-up time was 18 months (range, 7-71 months). A retrospective analysis was conducted to analyse the survival and recurrence data,and to explore the prognostic factors of NECUC. RESULTS: Thirteen patients died during the follow-up period. The cumulative progression-free survival (PFS) of 2 and 5 years were respectively 54.2% and 38.1%, and the estimated median PFS was 29 months. The cumulative overall survival (OS) of 2 and 5 years were respectively 56.1% and 44.9%, and the estimated median OS was 31 months. Fourteen cases had recurrence, and the median recurrence time was 9 months (range, 3-30 months). Recurrent or metastatic sites: 2 cases in pelvis, 4 cases in liver, 3 cases in lung, 3 cases in adrenal glands, 3 cases in bones, 2 cases in brain, 1 case in pancreas, 1 case in lymph nodes of para-aorta and neck, and 3 cases had metastasis in two or more organs. Thirteen cases with recurrence died of disease, and another one is alive with disease. The univariate analysis showed that lesion size of the cervix and FIGO stage were significant prognostic factors (P<0.01), while age, tumor components, deep invasion in cervical stromal, LVSI, pelvic and (or) para-aortic lymph nodes involvement, neoadjuvant chemotherapy, adjuvant radiotherapy and preserving ovaries were not significantly associated with prognosis (all P>0.05). CONCLUSION: The prognosis of NECUC in early-stage is poor and the lesion size of the cervix and FIGO stage are prognostic factors. PMID- 26268411 TI - [Clinicopathologic characteristics and risk factors for lung metastasis after radical hysterectomy in early-stage cervical cancer]. AB - OBJECTIVE: To discuss the clinicopathologic characteristics and risk factors for lung metastasis of early-stage cervical cancer after radical hysterectomy. METHODS: The complete clinicopathologic data of patients with lung metastasis of cervical cancer after radical surgery from January 2008 to December 2013 admitted in Zhejiang Cancer Hospital were retrospectively analyzed by univariate and multivariate analysis. RESULTS: (1) There were 38 cases of early cervical cancer suffered from lung metastasis after radical hysterectomy during the period. The median age at diagnosis of cervical cancer was 46 years, the average lung metastasis time was 13 months after operation, 50.0% (19/38) cases occurred in the first year. Thirty-one cases were squamous cell carcinoma and 7 cases were non-squamous cell carcinoma. (2) Univariate analysis showed that age, clinical stage, manner of tumor growth, tumor grade, perineuronal invasion, para-aortic lymph node metastasis were not significant effect on postoperative lung metastasis (all P>0.05). But tumor size, histologic types, depth of stromal invasion, uterine body infiltration, lympho-vascular space invasion,pelvic lymph node metastasis, positive margin and abnormal tumor markers were significantly correlated with postoperative lung metastasis (all P<0.05). Multivariate analysis showed that only tumor size, histologic types and pelvic lymph node metastasis were independent risk factors for lung metastasis of cervical cancer (P<0.05). CONCLUSIONS: Patients of early-stage cervical cancer with lung metastasis mostly occurs within 1 year after radical hysterectomy. Local large tumor lesions (tumor size >4 cm), non-squamous cell carcinoma and pelvic lymph node metastasis were more likely to have lung metastasis. PMID- 26268412 TI - [The natural history of cervical intraepithelial neoplasia I and the clinical significance of p16(INK4a) protein as a marker of progression in cervical intraepithelial neoplasia I]. AB - OBJECTIVE: To describe the natural history of cervical intraepithelial neoplasia (CIN) I and the biologic factors associated with the progression of CIN I and to analyze the predictive values of p16(INK4a) protein for the progression of CIN I. METHODS: From August 2010 to July 2013, 104 patients referred for abnormal cytology [<= low-grade squamous intraepithelial lesion (LSIL); including negative for intraepithelial lesion or malignancy (NILM), atypical squamous cells of undetermined significance (ASCUS), LSIL] and high-risk (HR) HPV positive, and were diagnosed CIN I by colposcopy-assisted biopsy and followed at 1-year intervals in the First Affiliated Hospital of Nanjing Medical University. In order to analyze the relationship between the progression of CIN I with clinical biologic factors, including patient age, cervical cytology before colposcopy, loads of HR HPV, HPV L1 capsid protein, p16(INK4a) protein, chi(2) tests was used to compare the different frequencies of factors in groups of progressed and persisted/regressed CIN I, then five factors with progressed CIN I were processed into binary logistic regression analysis. RESULTS: (1) In the first year of follow-up, among 104 patients (including 15 cases NILM, 78 cases ASCUS, 11 cases LSIL), 52 cases of them were NILM and HR HPV negative, 30 cases were negative for intraepithelial lesion, 10 cases were CIN I, 5 cases were CIN II and 7 cases were CIN III. In total, 82 cases (78.8%, 82/104) cases had regressed, 10 cases (9.6%, 10/104) persisted, 12 cases (11.5%, 12/104) progressed [including 5 cases (4.8% , 5/104) progressed to CIN II, 7 cases (6.7% , 7/104) progressed to CIN III, none progressed to invasive cancer]. (2) All patients, 88 cases of them accepted immunohistochemical detection the expression of p16(INK4a) protein. The result shown that 30 cases (34%, 30/88) were positive and 58 cases (66%, 58/88) were negative. And 94 cases accepted immunocytochemical detection the expression of HPV L1 capsid protein, 49 cases (52% , 49/94) were positive and 45 cases (48% , 45/94) were negative. (3) Univariate analysis showed that age of the patient, loads of HR HPV, cervical cytology before colposcopy and the expression of HPV L1 capsid protein were not risk factors of the progression of CIN I (all P>0.05) except for the expression of p16(INK4a) protein (P<0.05). Multivariable analysis found that p16(INK4a) protein positive was associated with progression of CIN I (OR=5.1, 95%CI: 1.162-22.387, P=0.031). (4) Thirty-one cases were p16(INK4a) protein positive, 8 cases (27%, 8/30) of them progressed, while 4 cases (7%, 4/58) of 58 cases with p16(INK4a) protein negative progressed,in which there were significant difference (P<0.05). The sensitivity was 75%, the specificity was 71%, the positive predictive value was 27% and the negative predictive value was 93% for progression to CIN II-III of p16(INK4a) protein staining. CONCLUSIONS: The progression rate of CIN I with abnormal cytology (<=LSIL) and HR HPV positive was lower, and there was no progression to invasion at 1-year intervals. Immunostaining of p16(INK4a) protein as the risk factors of CIN I progression could have a role in prediction of CIN I and the management of high-risk CIN I. PMID- 26268413 TI - Evolutionary suppression of erythropoiesis via the modulation of TGF-beta signalling in an Antarctic icefish. AB - The Antarctic icefish, a family (Channichthyidae) of teleosts within the perciform suborder Notothenioidei, are the only known vertebrates without oxygen transporting haemoglobins and that are largely devoid of circulating erythrocytes. To elucidate the evo-devo mechanisms underpinning the suppressed erythropoiesis in the icefish, we conducted comparative studies on the transcriptomes and microRNAomes of the primary haematopoietic tissues between an icefish (Chionodraco hamatus) and two red-blooded notothenioids (Trematomus bernacchii and Gymnodraco acuticeps). We identified substantial remodelling of the haematopoietic programs in the icefish through which erythropoiesis is selectively suppressed. Experimental verification showed that erythropoietic suppression in the icefish may be attributable to the upregulation of TGF-beta signalling, which coincides with reductions in multiple transcription factors essential for erythropoiesis and the upregulation of hundreds of microRNAs, the majority (> 80%) of which potentially target erythropoiesis regulating factors. Of the six microRNAs selected for verification, three miRNAs (miR-152, miR-1388 and miR-16b) demonstrated suppressive functions on GATA1 and ALAS2, which are two factors important for erythroid differentiation, resulting in reduced numbers of erythroids in microinjected zebra fish embryos. Codon substitution analyses of the genes of the TGF-beta superfamily revealed signs of positive selection in TGF beta1 and endoglin in the lineages leading to Antarctic notothenioids. Both genes are previously known to function in erythropoietic suppression. These findings implied a general trend of erythropoietic suppression in the cold-adapted notothenioid lineages through evolutionary modulation of the multi-functional TGF beta signalling pathway. This trend is more pronounced in the haemoglobin-less icefish, which may pre-emptively hinder the otherwise defective erythroids from production. PMID- 26268414 TI - In vivo magnetization transfer imaging of the lung using a zero echo time sequence at 4.7 Tesla in mice: Initial experience. AB - PURPOSE: The aim of the present study was to assess the feasibility of magnetization transfer-prepared zero echo time (ZTE) imaging of the lung in vivo at high field strength [4.7 Tesla) T] in mice. METHODS: Eighteen C57BL/10 mice underwent MRI examinations in a 4.7T MR-scanner. A three-dimensional ZTE sequence was applied for lung imaging combined with a Gaussian MT-prepulse, which was followed by a train of 100 ZTE imaging readouts. Degree of MT was assessed by calculation of the magnetization transfer ratio (MTR). Direct saturation was estimated using Bloch equation simulations based on T1 measurements. The line width of pulmonary tissue was estimated using T2* measurements. RESULTS: Experimental MTR-values of nonpulmonary tissues obtained with ZTE exhibited the characteristics known from conventional MT-sequences (skeletal muscle and liver: high values; fatty tissue: low values). Lung tissue demonstrated MTR-values in between fatty tissue and liver tissue. Direct saturation could be estimated by the Bloch simulation; however, an adequate approximation was only possible for T2 values nearly in the range of parenchymal organs. CONCLUSION: Pulmonary MT measurements at high field strength using the proposed MT-ZTE sequence is feasible; however, estimation of direct saturation remains challenging. Magn Reson Med 76:156-162, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26268415 TI - Evaluation of the 2008 World Health Organization classification for non-mycosis fungoides, non-Sezary syndrome T/NK-cell lymphomas with primary cutaneous involvement. AB - BACKGROUND: Cutaneous non-mycosis fungoides non-Sezary syndrome T/NK cell lymphomas (non-MF/non-SS CTCL) are rare. In 2005, a consensus of the World Health Organization (WHO) and European Organization for Research and Treatment of Cancer (EORTC) classifications for primary cutaneous lymphomas was established. These guidelines were then adopted into the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 2008. This study aims to assess the applicability of the WHO 2008 classification in a retrospective series of CTCL cases registered in a reference academic center in Brazil. METHODS: Twenty-seven patients with non-MF/non-SS CTCL were studied. Clinical, histopathological and immunophenotypical features based on an extensive panel of antibodies were applied to classify the cases according to the WHO, 2008. RESULTS: Overall, diagnostic categories included eight (29.6%) cutaneous anaplastic large-cell lymphoma, five (18.5%) lymphomatoid papulosis, six (22.2%) extranodal natural killer (NK)/T-cell lymphoma, nasal type, five (18.5%) adult T-cell leukemia/lymphoma, one (3.7%) cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma and two (7.4%) of peripheral T-cell lymphoma not otherwise specified (NOS). CONCLUSIONS: The WHO classification (2008) was applicable to most cases of non-MF/non-SS CTCL, while some cases remained unclassified and were considered NOS-peripheral T-cell lymphoma. An unexpected high frequency of NK/T-cell lymphoma nasal type was observed. PMID- 26268416 TI - Natural antimicrobials and high-pressure treatments on the inactivation of Salmonella Enteritidis and Escherichia coli O157:H7 in cold-smoked salmon. AB - BACKGROUND: High hydrostatic pressure (HHP) combined with reuterin and lactoperoxidase system (LPS) has exerted antimicrobial activity against Listeria monocytogenes in cold-smoked salmon at chilled temperatures. Therefore the purpose of this work was to evaluate the effect of HHP combined with reuterin, LPS and lactoferrin (LF) on the survival of Salmonella enterica subsp. enterica serovar Enteritidis and Escherichia coli O157:H7 in cold-smoked salmon stored at 4 and 10 degrees C. RESULTS: Salmonella Enteritidis and E. coli O157:H7 were reduced more than 3 log colony-forming units (CFU) g(-1) by the pressure treatment (450 MPa/5 min). LPS slightly diminished pathogen levels throughout storage, whereas no effect was recorded when reuterin or LF was added. The Salmonella population was below the detection limit (<1 log CFU g(-1) ) during the storage of HHP-treated smoked salmon at 4 and 10 degrees C. The antimicrobial activity of HHP against E. coli O157:H7 was increased when 450 MPa was applied in combination with LPS in cold-smoked salmon at 4 and 10 degrees C. CONCLUSION: HHP at 450 MPa/5 min inactivated S. Enteritidis in cold-smoked salmon and in combination with LPS would be useful as a hurdle technology approach against E. coli O157:H7, even under mild temperature abuse conditions. (c) 2015 Society of Chemical Industry. PMID- 26268417 TI - Increased expression of metalloproteinase-2 and -9 (MMP-2, MMP-9), tissue inhibitor of metalloproteinase-1 and -2 (TIMP-1, TIMP-2), and EMMPRIN (CD147) in multiple myeloma. AB - INTRODUCTION: Activity of metalloproteinases (MMP) is controlled both by specific tissue inhibitors (TIMP) and activators (extracellular matrix metalloproteinase inducer, EMMPRIN). There are few data available concerning concentration the bone marrow of MMP-2, MMP-9, TIMP-1, and TIMP-2, or EMMPRIM expression by bone marrow mesenchymal stromal cells (BMSCs) in patients with multiple myeloma (MM). PATIENTS AND METHODS: We studied 40 newly diagnosed, untreated patients: 18 males and 22 females with de novo MM and 11 healthy controls. Bone marrow was collected prior to therapy. BMSCs were derived by culturing bone marrow cells on MesenCult. Protein concentrations were determined in bone marrow plasma and culture supernatants by ELISA. EMMPRIN expression by BMSCs was assessed by flow cytometry. RESULTS: The median concentrations of MMP-9, TIMP-1, and TIMP-2 in both marrow plasma and culture supernatants were significantly higher in MM patients than controls. CONCLUSION: EMMPRIN expression and ratios MMP-9/TIMP-1 and MMP-2/TIMP-2 were higher in MM patients, our results demonstrate that in MM patients MMP-2 and MMP-9 are secreted in higher amounts and are not balanced by inhibitors. PMID- 26268418 TI - Histology and Immunohistochemistry of the Cardiac Ventricular Structure in the Green Turtle (Chelonia mydas). AB - This study describes the implications of cardiac ventricular microscopy in Chelonia mydas relating to its ability to dive. For this work, 11 specimens of the marine turtle species C. mydas found dead on the coast of Rio Grande do Norte (Northeast Brazil) were used. After necropsy, fragments of the cardiac ventricular wall were fixed in 10% buffered formaldehyde solution for 24 h and then subjected to routine processing for light and scanning electron microscopy (SEM). The ventricle in this species is formed by the epicardium, myocardium and endocardium. The subepicardial layer consists of highly vascularised connective tissue that emits septa to reinforce the myocardium surface. There is an abundant and diffuse subepicardial nerve plexus shown by immunostaining technique. The thickness of the spongy myocardium and the nature of its trabeculae varied between the heart chambers. The endocardium shows no characteristic elements of the heart conduction system. The valves have a hyaline cartilage skeleton, coated by dense irregular connective tissues characterised by elastic fibres. These findings in the green turtle ventricular microscopy are related to hypoxia resistance during diving. PMID- 26268419 TI - Crawford Williamson Long: The True Pioneer of Surgical Anesthesia. AB - Anesthesia and analgesia are as old as mankind itself. However, we now know that the true pioneer of surgical anesthesia through inhalation of ether was Doctor Crawford Williamson Long (1815-1878), who endeavored to help his profession and mankind without pursuing any reward or honor. Crawford Williamson Long was a great and beloved American surgeon. He was a well-educated and elegant man with an outstanding personality. Crawford was born in Danielsville, Georgia, in the United States and was the son of James Long and Elizabeth Ware Long. He married Mary Caroline Swain Long and gave birth to 12 children. Long proved the effectiveness of ether after painlessly removing a tumor from the neck. In 1847, a rivalry broke out among Horace Wells, Charles Thomas Jackson, and William Thomas Green Morton for the primacy as regards the discovery of anesthesia. The US Congress offered itself to arbitrate the case of the so called "ether controversy." Finally, a few years after the end of the North American Civil War, while taking care of a patient, Crawford passed away, presumably after suffering a stroke. PMID- 26268420 TI - Schlafen 3 Mediates the Differentiating Effects of Cdx2 in Rat IEC-Cdx2L1 Enterocytes. AB - AIM: Mature, differentiated enterocytes are essential for normal gut function and critical to recovery from pathological conditions. Little is known about the factors that regulate intestinal epithelial cell differentiation in the adult intestine. The transcription factor, Cdx2, involved in enterocytic differentiation, remains expressed in the adult. Since we have implicated Slfn3 in differentiation in vivo and in vitro, we examined whether it also mediated differentiation in the IEC-Cdx2-L1 cell model of differentiation. MATERIALS AND METHODS: IEC-Cdx2-L1 cells, permanently transfected with Cdx2 under the control of isopropyl-beta-D-thiogalactoside (IPTG), were stimulated to differentiate by 16-day exposure to IPTG. Transcript levels of Cdx2, Slfn 3, and villin were determined by quantitative reverse transcriptase-polymerase chain reaction of mRNA isolated from IPTG-treated and control cells. Slfn3 expression was lowered with specific siRNA to investigate the role of Slfn3 in Cdx2-driven villin expression in IPTG-differentiated cells. RESULTS: Slfn3 and villin expression were significantly greater in IPTG-treated cells. Slfn3 siRNA lowered Slfn3 expression and abolished the IPTG-induced rise in villin expression (p < .05 by ANOVA); Cdx2 expression was unaffected by Slfn3 siRNA. DISCUSSION: The data indicate that the presence of Slfn3 is required for Cdx2 to induce villin expression, and thus differentiation. However, Slfn3 must also promote differentiation of Cdx2 independently since IEC-6 cells that do not normally express Cdx2 can be differentiated by a variety of Slfn3-dependent mechanisms. PMID- 26268421 TI - Comparison of Surgical versus Non-Surgical Treatment of Displaced 3- and 4-Part Fractures of the Proximal Humerus: A Meta-Analysis. AB - PURPOSE/AIM: This meta-analysis compares the clinical outcomes of surgical versus conservative treatment of displaced, 3- or 4-part, proximal humeral fractures. MATERIALS AND METHODS: Medline, Cochrane, EMBASE, and Google Scholar were searched for studies published until October 2013, reporting functional outcomes of 3- or 4-part fractures of the proximal humerus in skeletally mature patients. Only randomized controlled trials were included. The treatments that were evaluated included non-surgical, open surgery, intramedullary pin, locking plate, arthroplasty, and minimally invasive surgical treatments. A meta-analysis was performed on the difference in functional outcomes and quality of life (QoL) between participants undergoing surgical versus non-surgical treatment. RESULTS: Out of 254 participants in the studies who were analyzed, 127 were treated surgically. The difference in mean values of functional score showed similar results between surgical and non-surgical treatments (difference in mean values = 0.015, 95% CI = -0.232 to 0.261, p = .908).The difference in mean values of QoL showed that surgical treatment provided better post-operative QoL than non surgical treatment (difference in mean values = 0.146, 95% CI = 0.052 to 0.240, p = .002). CONCLUSIONS: Surgical treatment of displaced, multi-fragment fractures of the proximal humerus did not improve shoulder functional outcome, based on the Constant-Murley Score, when compared with conservative and non-surgical treatments. However, health-related QoL was significantly improved with surgical treatment compared with conservative treatment. PMID- 26268422 TI - Meta-Analysis on Microdiscectomy and Sequestrectomy for Lumbar Disc Herniation. AB - PURPOSE: Lumbar disc herniation (LDH) is a common cause of low back pain and mainly occurs in patients aged 24 to 45 years. To further compare the efficacy of microdiscectomy and sequestrectomy, we made quantitative evaluation of clinical studies published so far by meta-analysis in order to provide information for clinical decision. METHODS: Literatures reporting randomized controlled studies that compared the efficacy of microdiscectomy and sequestrectomy for LDH were retrieved from major databases using predefined inclusion and exclusion criteria. RESULTS: Meta-analysis showed that microdiscectomy resulted in higher low back pain VAS score (standard mean difference, SMD = 0.86, 95% confidential interval, CI: 0.19, 1.53; P = 0.01) and there was not statistically significant difference in the incidence of re-operation (odd ratio, OR = 0.85, 95% CI: 0.46, 1.85; P = 0.60) and neuropathic pain VAS scores (SMD = 0.51, 95% CI: -0.16, 1.18; P = 0.14) between the methods. CONCLUSION: Both microdiscectomy and sequestrectomy had good curative results in the treatment of LDH. In low back pain VAS score, the former was better than the latter, while in the analgesic usage rate, the latter was superior to the former. In clinical practice, the choice of surgical method should be considered on the basis of actual situations. PMID- 26268423 TI - Helping Aged Victims of Crime (the HAVoC Study): Common Crime, Older People and Mental Illness--ERRATUM. AB - The author list previously published for this article was incomplete when received by the journal. It should also have included Gerard Leavey, University College London, UK, as an author, as follows: Marc Serfaty, Anna Ridgewell, Vari Drennan, Chris R. Brewin, Gerard Leavey, Anwen Wright, Gloria Laycock, Martin Blanchard. PMID- 26268424 TI - Bacterial isolates and their antimicrobial susceptibility pattern among patients with external ocular infections at Borumeda hospital, Northeast Ethiopia. AB - BACKGROUND: Bacteria are major cause of ocular infections and possible loss of vision. The emergence of antimicrobial resistant bacteria increases the risk of treatment failure with potentially serious consequences. The aim of this study was to determine the prevalence of bacterial isolates and their antimicrobial susceptibility pattern among patients with external ocular infections. METHODS: A cross sectional study was conducted among 160 patients with external ocular infections at Borumeda hospital, Northeast Ethiopia. Socio-demographic and clinical data were collected using structured questionnaire. External ocular specimens were collected using sterile swabs and inoculated on MacConkey agar, Chocolate agar and Blood agar culture Medias. Presumptive isolates were further identified by a series of biochemical tests. The antimicrobial susceptibility patterns of the isolates were determined by disk diffusion method. RESULT: The overall prevalence of bacterial pathogens among external ocular samples was 59.4 %. The majority of the isolates (93.7 %; 89/95) were Gram positive and the other 6.3 % (6/95) Gram negative bacteria. The proportion of coagulase negative Staphylococci among the Gram positive bacterial isolates was 53.7 % (n = 51/95). All Gram positive isolates were susceptible for vancomycin but 67.4 % (n = 60/95) of them were resistant against amoxicillin. Moreover, drug resistance to tetracycline, norfloxacylin, ceftriaxone and ciprofloxacin were observed among Gram negative bacteria isolates. CONCLUSION: The prevalence of bacterial pathogens among external ocular samples was high and the predominant isolate was coagulase negative Staphylococci. Exceptionally high amoxicillin resistance was observed among Gram positive bacterial isolates that may dictate to conduct drug susceptibility test routinely. PMID- 26268425 TI - Association of Online Health Information-Seeking Behavior and Self-Care Activities Among Type 2 Diabetic Patients in Saudi Arabia. AB - BACKGROUND: Health information obtained from the Internet has an impact on patient health care outcomes. There is a growing concern over the quality of online health information sources used by diabetic patients because little is known about their health information-seeking behavior and the impact this behavior has on their diabetes-related self-care, in particular in the Middle East setting. OBJECTIVE: The aim of this study was to determine the online health related information-seeking behavior among adult type 2 diabetic patients in the Middle East and the impact of their online health-related information-seeking behavior on their self-care activities. METHODS: A cross-sectional survey was conducted on 344 patients with type 2 diabetes attending inpatient and outpatient primary health care clinics at 2 teaching hospitals in Riyadh, Saudi Arabia. The main outcome measures included the ability of patients to access the Internet, their ability to use the Internet to search for health-related information, and their responses to Internet searches in relation to their self-care activities. Further analysis of differences based on age, gender, sociodemographic, and diabetes-related self-care activities among online health-related information seekers and nononline health-related information seekers was conducted. RESULTS: Among the 344 patients, 74.1% (255/344) were male with a mean age of 53.5 (SD 13.8) years. Only 39.0% (134/344) were Internet users; 71.6% (96/134) of them used the Internet for seeking health-related information. Most participants reported that their primary source of health-related information was their physician (216/344, 62.8%) followed by television (155/344, 45.1%), family (113/344, 32.8%), newspapers (100/344, 29.1%), and the Internet (96/344, 27.9%). Primary topics participants searched for were therapeutic diet for diabetes (55/96, 57%) and symptoms of diabetes (52/96, 54%) followed by diabetes treatment (50/96, 52%). Long history of diabetes, familial history of the disease, unemployment, and not seeking diabetes education were the most common barriers for online health-related information-seeking behavior. Younger age, female, marital status, higher education, higher income, and longer duration of Internet usage were associated with more online health-related information-seeking behaviors. Most (89/96, 93%) online health-related information seekers reported positive change in their behaviors after seeking online health information. Overall odds ratio (OR 1.56, 95% CI 0.63-3.28) for all self-care responses demonstrated that there was no statistically significant difference between those seeking health-related information online and non-health-related information seekers. However, health-related information seekers were better in testing their blood glucose regularly, taking proper action for hyperglycemia, and adopting nonpharmacological management. CONCLUSIONS: Physicians and television are still the primary sources of health-related information for adult diabetic patients in Saudi Arabia whether they seek health-related information online or not. This study demonstrates that participants seeking online health-related information are more conscious about their diabetes self-care compared to non-health-related information seekers in some aspects more than the others. PMID- 26268426 TI - Hypertension subtypes and risk of cardiovascular diseases in a Mongolian population, inner Mongolia, China. AB - BACKGROUND: There have been no reports about the effects of hypertension subtypes on the future cardiovascular events among Mongolian people, China. METHODS AND RESULTS: From June 2003 to July 2012, we conducted a prospective study to assess the association of hypertension subtypes with future risk of cardiovascular events including stroke and coronary heart disease among a Mongolian cohort of 2589 adults in China. According to the baseline blood pressure levels, the subjects were divided into those with normal blood pressure, prehypertension, isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and combined systolic and diastolic hypertension (SDH). Cox proportional hazards models were used to evaluate the association between blood pressure subtypes and risk of cardiovascular diseases. After adjustment for age and gender, hazard ratios (95% confidence intervals) of cardiovascular diseases were 1.75 (0.92 3.33), 2.11 (0.95-4.70), 2.14 (1.01-4.56) and 5.31 (2.86-9.77) for pre hypertension, ISH, IDH and SDH, respectively, compared with normal blood pressure. Furthermore, after adding other cardiovascular risk factors to adjustment, hazard ratios (95% confidence intervals) of cardiovascular diseases were 1.74 (0.92-3.31), 2.00 (0.88-4.54), 2.20 (1.02-4.74) and 4.92 (2.62-9.26) for pre-hypertension, ISH, IDH and SDH, respectively, compared with the normal blood pressure group. CONCLUSIONS: IDH and SDH were significantly associated with the increased risk of cardiovascular diseases; this study suggests that carefully monitoring and actively treating the subjects with IDH should be an important strategy for CVD prevention among Mongolian population. PMID- 26268428 TI - Aluminum Redistribution during the Preparation of Hierarchical Zeolites by Desilication. AB - A literature survey reveals a prominent reduction in the concentration of Bronsted acid sites in hierarchically organized zeolites with increasing mesoporous or external surface area independent of the framework type or synthesis route; this suggests a common fundamental explanation. To determine the cause, nature, and impact of the underlying changes in aluminum speciation, this study combines a multitechnique analysis that integrates basic characterization, a detailed synchrotron XRD and multiple-quantum NMR spectroscopy assessment, and catalytic tests to correlate evolution of the properties with performance during successive steps in the preparation of hierarchical MFI-type zeolites by desilication. The findings, subsequently generalized to FAU- and BEA-type materials, identify the crucial impact of calcination on the protonic form, which is an integral step in the synthesis and regeneration of zeolite catalysts; on aluminum coordination; and the associated acidity trends. PMID- 26268427 TI - Grade of dysplasia and malignant transformation in adults with premalignant laryngeal lesions. AB - BACKGROUND: The purpose of this systematic review was to determine the significance of the grade of dysplasia in the development of invasive carcinoma. METHODS: A systematic search was performed to identify all relevant evidence. Titles and abstracts were screened using predefined criteria. Remaining articles were critically appraised. Absolute risks and 95% confidence intervals (CIs) were calculated. RESULTS: Seven articles were included. Four studies demonstrated an increased risk for the development of laryngeal carcinoma from mild, moderate, and severe dysplasia. Three studies showed an increased risk between the categories of mild and moderate dysplasia. CONCLUSION: The risk of malignant transformation seems to increase with the grade of dysplasia, although percentages between studies are highly dissimilar. The wide variety and overlapping 95% CIs make it difficult to formulate a strong recommendation. However, moderate dysplasia is more prone for malignant transformation than previously thought, which might influence follow-up and treatment decisions in the future. (c) 2015 Wiley Periodicals, Head Neck 38: E2284-E2290, 2016. PMID- 26268430 TI - Chain-like structure elements in Ni40Ta60 metallic glasses observed by scanning tunneling microscopy. AB - The structure of metallic glasses is a long-standing question because the lack of long-range order makes diffraction based techniques difficult to be applied. Here, we used scanning tunneling microscopy with large tunneling resistance of 6 GOmega at low temperature in order to minimize forces between probe and sample and reduce thermal fluctuations of metastable structures. Under these extremely gentle conditions, atomic structures of Ni40Ta60 metallic glasses are revealed with unprecedented lateral resolution. In agreement with previous models and experiments, icosahedral-like clusters are observed. The clusters show a high degree of mobility, which explains the need of low temperatures for stable imaging. In addition to icosahedrons, chain-like structures are resolved and comparative density functional theory (DFT) calculations confirm that these structures are meta-stable. The co-existence of icosahedral and chain-like structures might be an key ingredient for the understanding of the mechanical properties of metallic glasses. PMID- 26268431 TI - Sudden insight is associated with shutting out visual inputs. AB - Creative ideas seem often to appear when we close our eyes, stare at a blank wall, or gaze out of a window--all signs of shutting out distractions and turning attention inward. Prior research has demonstrated that attention-related brain areas are differently active when people solve problems with sudden insight (the Aha! phenomenon), relative to deliberate, analytic solving. We directly investigated the relationship between attention deployment and problem solving by recording eye movements and blinks, which are overt indicators of attention, as people solved short, visually presented problems. In the preparation period, before problems eventually solved by insight, participants blinked more frequently and longer, and made fewer fixations, than before problems eventually solved by analysis. Immediately prior to solutions, participants blinked longer and looked away from the problem more often when solving by insight than when solving analytically. These phenomena extend prior research with a direct demonstration of dynamic differences in attention as people solve problems with sudden insight versus analytically. PMID- 26268432 TI - Pharmacokinetics of a multicomponent herbal preparation in healthy Chinese and African volunteers. AB - K-601 is an herbal formulation for influenza consisting of Lonicera japonica, Isatis indigotica, Rheum palmatum, Phellodendron chinense, and Scutellaria baicalensis. In this work, we characterized the chemical constituents in K-601, identified the absorbed compounds and determined their pharmacokinetics in 6 Chinese and African volunteers by liquid chromatography with time-of-flight mass spectrometry. Similarity evaluation for chromatographic fingerprint of nine different batches showed values above 0.983. Totally, 50 components were identified in K-601. Then, 15 major prototype compounds and 17 metabolites were identified in human plasma. Major metabolic pathways included glucuronidation, sulfation, methylation, demethylation, and reduction. The pharmacokinetics of the most abundant prototype compounds, berberine, jatrorrhizine, palmatine and magnoflorine were determined. Significant pharmacokinetic differences were observed between the African and Chinese subjects. The AUCs of the African is about 4-10 fold higher than that of the Chinese for the three benzylisoquinoline alkaloids. Magnoflorine, an aporphine alkaloid, was absorbed better in the Chinese than in the African. The biotransformation of K-601 by human intestinal microflora was also investigated. The major reactions included hydroxylation, methylation, demethylation, acetylation and reduction. Glucuronidation and sulfation were not observed with fecal flora. These results may be important and useful in linking data from pharmacological assays and clinical effects. PMID- 26268433 TI - Rodents as pre-clinical models for predicting vaccine performance in humans. AB - Vaccines represent a key building block for establishing a successful and sustainable control strategy against infectious diseases. Vaccine development often depends on the availability of correlates for protection and reliable animal models for the screening, selection and prioritization of potential vaccine candidates. This is performed according to their immunogenicity, efficacy and safety profiles in pre-clinical studies, which are also critical for identification of candidate antigens, selection of an optimal delivery system and design of appropriate vaccine formulations. Thus, pre-clinical studies in animal models are a prerequisite for addressing crucial issues and generating a solid pre-clinical package for the approval of clinical trials. This review addresses the strengths, limitations and perspectives of rodents as a vaccine development and pre-clinical validation tool. PMID- 26268435 TI - Selecting the reference image for registration of CEST series. AB - BACKGROUND: To compare different reference images selected for registration among chemical exchange saturation transfer (CEST) series. MATERIALS AND METHODS: Five normal volunteers and eight brain tumor patients were studied on a 3 Tesla scanner. Image registration was performed by choosing each of the acquired CEST saturation or unsaturation dynamic images as the reference. CEST images at 3.5 ppm (amide proton transfer, APT) were computed for each motion-corrected data set after main magnetic field inhomogeneity correction. A uniformity index was defined to quantify the efficacy of image registration using different reference images. Joint histograms and the structural similarity index (SSIM) were used to analyze the intrinsic image similarity between various dynamic images. RESULTS: Image registration increased the average uniformity index by 18% if the 3.5 ppm saturated image was selected as the reference image. However, registering to the unsaturated dynamic image reduced the uniformity index by 13% on average. The joint histogram analysis showed that the saturated dynamic images were highly similar (SSIM = 0.89 +/- 0.01), and were considerably different from the unsaturated dynamic image (SSIM = 0.58 +/- 0.03). CONCLUSION: The selection of the 3.5 ppm dynamic image as the reference image generated the highest uniformity index for APT imaging though other saturated images were equally suited as reference images. PMID- 26268436 TI - Empowering vulnerable parents through a family mentoring program. AB - Evidence suggests that mentoring programs can foster positive relationships through role modelling, social support and opportunities to develop new skills. Home visiting programs, where a health professional or volunteer provides parenting support and companionship to at-risk families, have received attention from the health and welfare sector. These programs tend to focus on new mothers and immediate parenting concerns, and do not address broader social determinants of health that impact on the well being and functionality of the family. Herein we report on an evaluation of the Creating Opportunities and Casting Hope (COACH) program, a family mentoring program for vulnerable parents. COACH seeks to break cycles of generational poverty by addressing social determinants, such as housing, employment, health, finances and social support. A mixed-methods approach was used to evaluate the program, involving semistructured interviews with parents (n = 12), surveys with mentors (n = 27) and client case report review (n = 27). Parents experienced improvements in their housing and employment situations, family dynamics, social support and mental health, and decreased drug and alcohol use. Mentors described providing guidance on parenting strategies, financial management and domestic skills. Partnerships with local schools, health services and welfare agencies were vital in the referral processes for families, thereby building a community network of support and care. The COACH model of mentoring highlights the benefits of a flexible and long-standing program to address the social determinants of child health through the family environment and wider social and economic factors. PMID- 26268434 TI - Applications of bacillus Calmette-Guerin and recombinant bacillus Calmette-Guerin in vaccine development and tumor immunotherapy. AB - Bacillus Calmette-Guerin (BCG) vaccines are attenuated live strains of Mycobacterium bovis and are among the most widely used vaccines in the world. BCG is proven to be effective in preventing severe infant meningitis and miliary tuberculosis. Intravesical instillation of BCG is also a standard treatment for non-muscle invasive bladder cancer. In the past few decades, recombinant BCG (rBCG) technology had been extensively applied to develop vaccine candidates for a variety of infectious diseases, including bacterial, viral, and parasite infections, and to improve the efficacy of BCG in bladder cancer therapy. This review is intended to show the vast applications of BCG and recombinant BCG (rBCG) in the prevention of infectious diseases and cancer immunotherapy, with a special emphasis on recent approaches and trends on both pre-clinical and clinical levels. PMID- 26268437 TI - Regulation of kisspeptin and gonadotropin-releasing hormone expression in rat placenta: study using primary cultures of rat placental cells. AB - BACKGROUND: Gonadotropin-releasing hormone (GnRH) and kisspeptin in the hypothalamus are thought to be crucial components of the hypothalamic-pituitary gonadal (HPG) axis and maintain reproductive function. These neuropeptides are also expressed in the placenta, where they may contribute to placental physiology. In this study, we examined how these peptides are regulated within the placenta. METHODS: We used primary cultures of placental tissue from rats of 16-18 days gestation. After stimulation with estradiol, GnRH, kisspeptin, and neurokinin B (NKB), changes in placental GnRH, kisspeptin, and human chorionic gonadotropin (hCG) mRNA expression were evaluated by real-time quantitative RT PCR analysis. RESULTS: Immunocytochemical analysis showed that rat placental cells contained cells expressing kisspeptin or GnRH. GnRH and kisspeptin mRNA expression was significantly increased in placental cells in the presence of estradiol; NKB mRNA expression was also stimulated by estradiol. Stimulation of the cells with kisspeptin failed to stimulate GnRH mRNA expression. Conversely, both GnRH itself and NKB increased GnRH mRNA expression. Kisspeptin mRNA expression was not increased by kisspeptin itself; however, GnRH and NKB significantly increased kisspeptin mRNA expression. hCG expression was increased in the presence of estradiol. In addition, kisspeptin, GnRH, and NKB could stimulate the expression of hCG mRNA in placental cells. CONCLUSIONS: Our experiments using primary cultures of rat placental cells showed that GnRH, kisspeptin, and NKB expression was enhanced by estradiol, and unlike in the hypothalamus, kisspeptin did not control the expression of GnRH in placental cells. NKB might be located upstream of kisspeptin and GnRH, and these neuropeptides might be involved in the induction of hCG expression in placental cells. PMID- 26268438 TI - NanoCAGE-XL and CapFilter: an approach to genome wide identification of high confidence transcription start sites. AB - BACKGROUND: Identifying the transcription start sites (TSS) of genes is essential for characterizing promoter regions. Several protocols have been developed to capture the 5' end of transcripts via Cap Analysis of Gene Expression (CAGE) or linker-ligation strategies such as Paired-End Analysis of Transcription Start Sites (PEAT), but often require large amounts of tissue. More recently, nanoCAGE was developed for sequencing on the Illumina GAIIx to overcome these difficulties. RESULTS: Here we present the first publicly available adaptation of nanoCAGE for sequencing on recent ultra-high throughput platforms such as Illumina HiSeq-2000, and CapFilter, a computational pipeline that greatly increases confidence in TSS identification. We report excellent gene coverage, reproducibility, and precision in transcription start site discovery for samples from Arabidopsis thaliana roots. CONCLUSION: nanoCAGE-XL together with CapFilter allows for genome wide identification of high confidence transcription start sites in large eukaryotic genomes. PMID- 26268440 TI - Direct bioresorbable vascular scaffold implantation: Feasibility and midterm results. AB - OBJECTIVES: To analyze the feasibility and safety of direct bioresorbable vascular scaffold (BVS) implantation without previous balloon dilation. BACKGROUND: Lesion preparation through predilation is recommended before BVS implantation. There is no information on the routine use of direct BVS implantation. METHODS AND RESULTS: One hundred fifty-three patients with a total of 200 coronary lesions, were treated with BVS. A baseline intravascular ultrasound study (IVUS) was performed in 171 lesions (86%), and after BVS implantation, the quality of scaffolding was assessed with an additional IVUS (83, 41%) or optical coherence tomography (77, 38%). Elective predilation was conducted in 50 lesions. In 150 lesions, direct BVS implantation was attempted. In 129 lesions (86%), the BVS was implanted successfully, and in the remaining 21 (14%), direct implantation failed. In these cases, the scaffolds were retrieved and successfully implanted after balloon angioplasty. Longer and C-type lesions, and a larger plaque burden, were associated with failure to directly cross the lesion. Balloon postdilation was needed in 34% of the lesions. Ten patients (6.6%) had a periprocedural myocardial infarction. One patient (0.6%) died 60 days after BVS implantation due to thrombosis of the scaffold. At follow-up, target lesion revascularisation was needed in eight patients (5%). After 12 +/- 3 months, the remaining patients were symptom-free. CONCLUSIONS: Direct BVS implantation is safe and feasible in most soft coronary plaques. PMID- 26268439 TI - p75(NTR)-dependent activation of NF-kappaB regulates microRNA-503 transcription and pericyte-endothelial crosstalk in diabetes after limb ischaemia. AB - The communication between vascular endothelial cells (ECs) and pericytes in the microvasculature is fundamental for vascular growth and homeostasis; however, these processes are disrupted by diabetes. Here we show that modulation of p75(NTR) expression in ECs exposed to high glucose activates transcription of miR 503, which negatively affects pericyte function. p75(NTR) activates NF-kappaB to bind the miR-503 promoter and upregulate miR-503 expression in ECs. NF-kappaB further induces activation of Rho kinase and shedding of endothelial microparticles carrying miR-503, which transfer miR-503 from ECs to vascular pericytes. The integrin-mediated uptake of miR-503 in the recipient pericytes reduces expression of EFNB2 and VEGFA, resulting in impaired migration and proliferation. We confirm operation of the above mechanisms in mouse models of diabetes, in which EC-derived miR-503 reduces pericyte coverage of capillaries, increased permeability and impaired post-ischaemic angiogenesis in limb muscles. Collectively, our data demonstrate that miR-503 regulates pericyte-endothelial crosstalk in microvascular diabetic complications. PMID- 26268442 TI - Adverse events during placebo vs. no drug administration--results of a randomised interventional trial in 160 volunteers. PMID- 26268441 TI - Handling of Copper and Copper Oxide Nanoparticles by Astrocytes. AB - Copper is an essential trace element for many important cellular functions. However, excess of copper can impair cellular functions by copper-induced oxidative stress. In brain, astrocytes are considered to play a prominent role in the copper homeostasis. In this short review we summarise the current knowledge on the molecular mechanisms which are involved in the handling of copper by astrocytes. Cultured astrocytes efficiently take up copper ions predominantly by the copper transporter Ctr1 and the divalent metal transporter DMT1. In addition, copper oxide nanoparticles are rapidly accumulated by astrocytes via endocytosis. Cultured astrocytes tolerate moderate increases in intracellular copper contents very well. However, if a given threshold of cellular copper content is exceeded after exposure to copper, accelerated production of reactive oxygen species and compromised cell viability are observed. Upon exposure to sub-toxic concentrations of copper ions or copper oxide nanoparticles, astrocytes increase their copper storage capacity by upregulating the cellular contents of glutathione and metallothioneins. In addition, cultured astrocytes have the capacity to export copper ions which is likely to involve the copper ATPase 7A. The ability of astrocytes to efficiently accumulate, store and export copper ions suggests that astrocytes have a key role in the distribution of copper in brain. Impairment of this astrocytic function may be involved in diseases which are connected with disturbances in brain copper metabolism. PMID- 26268443 TI - Iontophoresis driven concentrations of topically administered diclofenac in skeletal muscle and blood of healthy subjects. AB - PURPOSE: The present open single-centre, descriptive and comparative pharmacokinetic study aimed to investigate the efficacy of iontophoresis to enhance transdermal delivery by measuring concentration vs. time profiles of diclofenac in local tissue and in plasma in two separate study periods. METHODS: Period 1 determined diclofenac concentrations in both calf muscles simultaneously by using microdialysis after applying diclofenac gel topically as a single dose of 5 g with or without iontophoresis in eight healthy volunteers. In period 2, the same dose was applied to another 8 volunteers to determine plasma concentrations of diclofenac either with or without iontophoresis in a cross over design. RESULTS: In period 1, tissue concentrations were found to be under the limit of detection of 0.5 ng/ml both with and without iontophoresis in all subjects. In period 2, after iontophoresis in 75% of study participants, plasma concentrations of diclofenac could be determined, but only in 25% without iontophoresis. Although area under the concentration-time-curve (AUC, 187.97 +/- 315.92 vs. 22.92 +/- 42.44 ng*min/ml) and maximum concentration (Cmax, 2.06 +/- 3.79 vs. 0.22 +/- 0.41 ng/ml) values showed a numerically clear trend for higher values with iontophoresis compared to passive diffusion, no significant difference could be found due to high inter-individual variability. In total, 18.75% of all subjects presented adverse events. CONCLUSIONS: Despite a higher percentage of subjects showed detectable plasma levels of diclofenac after iontophoresis, iontophoresis failed to achieve potentially more effective topical concentrations. The typical mechanism of iontophoresis like electromigration, electroosmosis and increased subcutaneous circulation could be responsible for the results of the present observation. Additional clinical studies are needed to justify the transdermal delivery of diclofenac by using iontophoresis. PMID- 26268444 TI - A novel approach to teaching pharmacotherapeutics--feasibility of the learner centered student-run clinic. AB - Medical students should be better prepared for their future role as prescribers. A new educational concept to achieve this is learning by doing. This encompasses legitimate, context-based training and gives students responsibility as early as possible in their medical education. Student-run clinics (SRCs) are an example of this concept. AIM: Describe the development of a new SRC for insured patients, primarily focused on medical (pharmacotherapy) education, the learner-centered student-run clinic (LC-SRC), and its feasibility. METHODS: Teams each comprising of three students (first, third, and fifth year) performed consultations including proposing management plans, all under the supervision of an internist. Patients were voluntary selected from the internal medicine outpatient clinic for follow-up in the LC-SRC. Feasibility was evaluated using a set of questionnaires for patients, supervisors, and students. RESULTS: In total, 31 consultations were conducted; 31 students and 4 clinical specialists participated. A pharmacotherapeutic treatment plan was drawn up in 33 % of the consultations. Patients were content with the care provided and rated the consultation with a 7.9 (SD 1.21) (1(min)-10(max)). Supervisors regarded LC-SRC safe for patients with guaranteed quality of care. They found the LC-SRC a valuable tool in medical education although it was time-consuming. Students appreciated their (new) responsibility for patient care and considered the LC-SRC a very valuable extracurricular activity. DISCUSSION: The LC-SRC is feasible, and all participants considered it to be a valuable educational activity. It offers students the opportunity to learn in a real interprofessional and longitudinal setting for their future role as prescriber in clinical practice. The benefits and learner effects need to be investigated in a larger study with a longer follow-up. PMID- 26268445 TI - Development of interferon beta-neutralising antibodies in multiple sclerosis--a systematic review and meta-analysis. AB - PURPOSE: Interferon beta (IFN-beta) is the drug of choice for treatment of relapsing forms of multiple sclerosis and is known to reduce the frequency and severity of relapses. This systematic review determines the occurrence of neutralising antibodies (NAbs) against different formulations of IFN-beta: IFN beta-1a AvonexTM, IFN-beta-1a RebifTM and IFN-beta-1b Betaferon/BetaseronTM. METHODS: The databases used in the review included MEDLINE Ovid (from 1950 to March 2015), Embase Ovid (from 1980 to March 2015), CENTRAL on The Cochrane Library (2011, Issue 4) and ClinicalTrials.gov (from 1997 to March 2015). All studies that compared the efficacy of the different formulations of IFN-beta in patients with relapsing forms of multiple sclerosis including IFN-beta-1a AvonexTM, IFN-beta-1a RebifTM, IFN-beta-1b Betaferon/BetaseronTM and IFN-beta-1b ExtaviaTM were included. RESULTS: Assessment of randomised controlled trials demonstrated that AvonexTM was 76% less likely than RebifTM to lead to the formation of NAbs. AvonexTM was 88% less likely than Betaferon/BetaseronTM to lead to the formation of NAbs. Similar findings were also observed in the non randomised controlled studies, with AvonexTM having the lowest risk. The formation of NAbs was dose dependent: AvonexTM at 30 MUg was 64% less risky than AvonexTM at 60 MUg. CONCLUSIONS: Our data show that 2.0-18.9% of patients developed NAbs to AvonexTM, 16.5-35.4% of patients developed NAbs to RebifTM and 27.3-53.3% of patients developed NAbs to Betaferon/BetaseronTM. PMID- 26268447 TI - Is Seeing Believing? Perceptions of Wildfire Risk Over Time. AB - Ongoing challenges to understanding how hazard exposure and disaster experiences influence perceived risk lead us to ask: Is seeing believing? We approach risk perception by attending to two components of overall risk perception: perceived probability of an event occurring and perceived consequences if an event occurs. Using a two-period longitudinal data set collected from a survey of homeowners living in a fire-prone area of Colorado, we find that study participants' initial high levels of perceived probability and consequences of a wildfire did not change substantially after extreme wildfire events in the intervening years. More specifically, perceived probability of a wildfire changed very little, whereas the perceived consequences of a wildfire went up a bit. In addition, models of risk perceptions show that the two components of overall risk perception are correlated with somewhat different factors, and experience is not found to be one of the strongest correlates with perceived risk. These results reflect the importance of distinguishing the components of overall risk and modeling them separately to facilitate additional insights into the complexities of risk perceptions, factors related to perceived risk, and change in risk perceptions over time. PMID- 26268446 TI - The effects of spatial filtering and artifacts on electrocorticographic signals. AB - OBJECTIVE: Electrocorticographic (ECoG) signals contain noise that is common to all channels and noise that is specific to individual channels. Most published ECoG studies use common average reference (CAR) spatial filters to remove common noise, but CAR filters may introduce channel-specific noise into other channels. To address this concern, scientists often remove artifactual channels prior to data analysis. However, removing these channels depends on expert-based labeling and may also discard useful data. Thus, the effects of spatial filtering and artifacts on ECoG signals have been largely unknown. This study aims to quantify these effects and thereby address this gap in knowledge. APPROACH: In this study, we address these issues by exploring the effects of application of two types of unsupervised spatial filters and three methods of detecting signal artifacts using a large ECoG data set (20 subjects, four task conditions in each subject). MAIN RESULTS: Our results confirm that spatial filtering improves performance, i.e., it reduces ECoG signal variance that is not related to the task. They also show that removing artifactual channels automatically (using quantitatively defined rejection criteria) or manually (using expert opinion) does not increase the total amount of task-related information, but does avoid potential contamination from one or more noisy channels. Finally, applying a novel 'median average reference' filter does not require the elimination of artifactual channels prior to spatial filtering and still mitigates the influence of channels with channel-specific noise. Thus, it allows the investigator to retain more potentially useful task-related data. SIGNIFICANCE: In summary, our results show that appropriately designed spatial filters that account for both common noise and channel-specific noise greatly improve the quality of ECoG signal analyses, and that artifacts in only a single channel can result in profound and undesired effects on all other channels. PMID- 26268449 TI - Resistance-Mutation (N31) Effects on Drug Orientation and Channel Hydration in Amantadine-Bound Influenza A M2. AB - The mechanism of amantadine binding to the S31 variant of the M2 protein of Influenza A is well understood, but the reasons behind N31 M2 amantadine insensitivity remain under investigation. Many molecular dynamics studies have evaluated the influence of amantadine position within the channel pore on its ability to inhibit proton conductance in M2, but little is known about the influence of amantadine rotational orientation. Replica-exchange umbrella sampling, steered, and classic molecular dynamics simulations were performed on amantadine in the solid-state NMR structure of S31 M2 and an N31 M2 homologue, both in the homotetramer configuration, to explore the effects of the position and tilt angle of amantadine on inhibition of the M2 channel. Steered simulations show that amantadine rotates with the amine toward the bulk water as it passes into the hydrophobic entryway lined by Val27 side chains. Results from all simulation types performed indicate that amantadine has a strong, specific orientation with the amine turned inward toward the central cavity in the S31 M2 pore but has variable orientation and a strong propensity to remain outward pointing in N31 M2. Free energy profiles from umbrella sampling, measured relative to bulk water, show amantadine binds more strongly to the S31 M2 pore by 8 kcal/mol in comparison to amantadine in the N31 pore, suggesting that it can escape more readily from the N31 channel through the Val27 secondary gate, whereas it is captured by the S31 channel in the same region. Lower water density and distribution near amantadine in S31 M2 reveal that the drug inhibits proton conductance in S31 M2 because of its inward-pointing configuration, whereas in N31 M2, amantadine forms hydrogen bonds with an N31 side chain and does not widely occlude water occupancy in any configuration. Both amantadine's weaker binding to and weaker water occlusion in N31 M2 might contribute to its inefficacy as an inhibitor of the mutant protein. PMID- 26268450 TI - A critical role of toll-like receptor 2 (TLR2) and its' in vivo ligands in radio resistance. AB - The role of Toll-like receptor-2 (TLR2) in radio-resistance remained largely unknown. TLR2 knockout (TLR2(-/-)) mice received radiation of 6.5 Gy, and then were studied. We found that radiation resulted in more severe mortality and morbidity rates in TLR2(-/-) mice. The cause of death in TLR2(-/-) mice may be severe and persistent bone marrow cell loss. Injection of the TLR2 agonist Pam3CSK4 into wild type (WT) mice induced radio-resistance. Myd88(-/-) mice were more susceptible to radiation. In conclusion, our data indicate that, similar to TLR4, TLR2 plays a critical role in radio-resistance. PMID- 26268451 TI - Formulation Strategy for the Delivery of Cyclosporine A: Comparison of Two Polymeric Nanospheres. AB - A wide range of nanoparticles has been explored for the delivery of highly hydrophobic drugs, but very few publications provide comparative data of the performance of different nanoparticles. To address this need, this publication compares poly(lactic-co-glycolic acid) (PLGA) nanoparticles and nanospheres made from tyrosine-derived tri-block copolymers (termed TyroSpheres) for their respective performance as carriers for cyclosporine A (CSA). Using previously reported data on PLGA, we followed similar experimental protocols to evaluate the in vitro characteristics of TyroSpheres. Although there are some similarities between the two particle systems for the delivery of CSA, such as effective encapsulation and epidermal skin penetration, several differences were notable. First, the methods of preparation were different, i.e., self-assembly and emulsion-diffusion-evaporation process for TyroSpheres and PLGA, respectively. Second, TyroSpheres provided 7-day diffusion-controlled release, whereas PLGA nanoparticles provided >21-day erosion-controlled release. Third, the size of TyroSpheres was measured to be ~60-70 nm irrespective of drug loading, whereas the size of PLGA nanoparticles (~100-250 nm) was dependent on drug loading and the method of preparation. Overall, this publication provides a direct comparison between two different types of nanoparticles and illuminates the respective advantages and disadvantages, using CSA as a model for the release of highly hydrophobic drugs. PMID- 26268452 TI - When Does Neoadjuvant Chemotherapy Really Avoid Radiotherapy? Clinical Predictors of Adjuvant Radiotherapy in Cervical Cancer. AB - BACKGROUND: The aim of this study was to identify clinical variables that may predict the need for adjuvant radiotherapy after neoadjuvant chemotherapy (NACT) and radical surgery in locally advanced cervical cancer patients. METHODS: A retrospective series of cervical cancer patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB2-IIB treated with NACT followed by radical surgery was analyzed. Clinical predictors of persistence of intermediate- and/or high-risk factors at final pathological analysis were investigated. Statistical analysis was performed using univariate and multivariate analysis and using a model based on artificial intelligence known as artificial neuronal network (ANN) analysis. RESULTS: Overall, 101 patients were available for the analyses. Fifty-two (51 %) patients were considered at high risk secondary to parametrial, resection margin and/or lymph node involvement. When disease was confined to the cervix, four (4 %) patients were considered at intermediate risk. At univariate analysis, FIGO grade 3, stage IIB disease at diagnosis and the presence of enlarged nodes before NACT predicted the presence of intermediate- and/or high-risk factors at final pathological analysis. At multivariate analysis, only FIGO grade 3 and tumor diameter maintained statistical significance. The specificity of ANN models in evaluating predictive variables was slightly superior to conventional multivariable models. CONCLUSIONS: FIGO grade, stage, tumor diameter, and histology are associated with persistence of pathological intermediate- and/or high-risk factors after NACT and radical surgery. This information is useful in counseling patients at the time of treatment planning with regard to the probability of being subjected to pelvic radiotherapy after completion of the initially planned treatment. PMID- 26268453 TI - Dorsal Root Ganglion (DRG) Stimulation in the Treatment of Phantom Limb Pain (PLP). AB - OBJECTIVES: Phantom limb pain (PLP) is a neuropathic condition in which pain is perceived as arising from an amputated limb. PLP is distinct from, although associated with, pain in the residual limb and nonpainful phantom sensations of the missing limb. Its treatment is extremely challenging; pharmaceutical options, while commonly employed, may be insufficient or intolerable. Neuromodulatory interventions such as spinal cord stimulation have generated mixed results and may be limited by poor somatotopic specificity. It was theorized that dorsal root ganglion (DRG) neuromodulation may be more effective. MATERIALS AND METHODS: Patients trialed a DRG neurostimulation system for their PLP and were subsequently implanted if results were positive. Retrospective chart review was completed, including pain ratings on a 100-mm visual analogue scale (VAS) and patient-reported outcomes. RESULTS: Across eight patients, the average baseline pain rating was 85.5 mm. At follow-up (mean of 14.4 months), pain was rated at 43.5 mm. Subjective ratings of quality of life and functional capacity improved. Some patients reduced or eliminated pain medications. Patients reported precise concordance of the paresthesia with painful regions, including in their phantom limbs; in one case, stimulation eliminated PLP as well as nonpainful phantom sensations. Three patients experienced a diminution of pain relief, despite good initial outcomes. CONCLUSIONS: DRG neuromodulation may be an effective tool in treating this pain etiology. Clinical outcomes in this report support recent converging evidence suggesting that the DRG may be the site of PLP generation and/or maintenance. Further research is warranted to elucidate mechanisms and optimal treatment pathways. PMID- 26268455 TI - Nosocomial empyema caused by a rare serotype, serotype 4c, of Listeria monocytogenes in a patient with rheumatoid arthritis and chronic kidney disease: A case report and review of the literature. AB - The intracellular pathogen Listeria monocytogenes presents characteristically as meningoencephalitis and bacteremia. Herein, we report an extremely rare case of empyema caused by serotype 4c L. monocytogenes in an immunocompromised patient. This case supports the inclusion of L. monocytogenes infection in the differential diagnosis of empyema in an immunocompromised patient. PMID- 26268454 TI - Versatility of using major histocompatibility complex class II dextramers for derivation and characterization of antigen-specific, autoreactive T cell hybridomas. AB - Antigen-specific, T cell hybridomas are useful to study the cellular, molecular and functional events, but their generation is a lengthy process. Thus, there is a need to develop robust methods to generate the hybridoma clones rapidly in a short period of time. To this end, we have demonstrated a novel approach using major histocompatibility complex (MHC) class II dextramers to generate T cell hybridomas for an autoantigen, proteolipid protein (PLP) 139-151. Using MHC class II dextramers assembled with PLP 139-151 as screening and sorting tools, we successfully obtained mono antigen-specific clones within seven to eight weeks. In conjunction with other T cell markers, dextramers permitted phenotypic characterization of hybridoma clones for their antigen specificity in a single step by flow cytometry. Importantly, we achieved successful fusions using dextramer(+) cells sorted by flow cytometry as a starting population, resulting in direct identification of multiple antigen-specific clones. Characterization of selected clones led us to identify chemokine receptor, CCR4(+) to be expressed consistently, but their cytokine-producing ability was variable. Our work provides a proof-of principle that the antigen-specific, CD4 T cell hybridoma clones can be generated directly using MHC class II dextramers. The availability of hybridoma clones that bind dextramers may serve as useful tools for various in vitro and in vivo applications. PMID- 26268456 TI - XUV excitation followed by ultrafast non-adiabatic relaxation in PAH molecules as a femto-astrochemistry experiment. AB - Highly excited molecular species are at play in the chemistry of interstellar media and are involved in the creation of radiation damage in a biological tissue. Recently developed ultrashort extreme ultraviolet light sources offer the high excitation energies and ultrafast time-resolution required for probing the dynamics of highly excited molecular states on femtosecond (fs) (1 fs=10(-15) s) and even attosecond (as) (1 as=10(-18) s) timescales. Here we show that polycyclic aromatic hydrocarbons (PAHs) undergo ultrafast relaxation on a few tens of femtoseconds timescales, involving an interplay between the electronic and vibrational degrees of freedom. Our work reveals a general property of excited radical PAHs that can help to elucidate the assignment of diffuse interstellar absorption bands in astrochemistry, and provides a benchmark for the manner in which coupled electronic and nuclear dynamics determines reaction pathways in large molecules following extreme ultraviolet excitation. PMID- 26268457 TI - Strengthened currents override the effect of warming on lobster larval dispersal and survival. AB - Human-induced climate change is projected to increase ocean temperature and modify circulation patterns, with potential widespread implications for the transport and survival of planktonic larvae of marine organisms. Circulation affects the dispersal of larvae, whereas temperature impacts larval development and survival. However, the combined effect of changes in circulation and temperature on larval dispersal and survival has rarely been studied in a future climate scenario. Such understanding is crucial to predict future species distributions, anticipate ecosystem shifts and design effective management strategies. We simulate contemporary (1990s) and future (2060s) dispersal of lobster larvae using an eddy-resolving ocean model in south-eastern Australia, a region of rapid ocean warming. Here we show that the effects of changes in circulation and temperature can counter each other: ocean warming favours the survival of lobster larvae, whereas a strengthened western boundary current diminishes the supply of larvae to the coast by restricting cross-current larval dispersal. Furthermore, we find that changes in circulation have a stronger effect on connectivity patterns of lobster larvae along south-eastern Australia than ocean warming in the future climate so that the supply of larvae to the coast reduces by ~4% and the settlement peak shifts poleward by ~270 km in the model simulation. Thus, ocean circulation may be one of the dominant factors contributing to climate-induced changes of species ranges. PMID- 26268458 TI - Receptor tyrosine kinase Kit action in skin melanocytes: is it exclusively cell autonomous? PMID- 26268460 TI - 'Reference rot': a developing problem in Emergency Medicine Australasia. PMID- 26268459 TI - Effect of Ginkgo biloba extract on experimental cardiac remodeling. AB - BACKGROUND: To investigate the ameliorated effects of an extract of Ginkgo biloba extract (GBE) on experimental cardiac remodeling in rats induced by acute cardiac infarction, and further explore the mechanism concentrated on myocardial type I collagen, transforming growth factor beta 1 (TGF-beta1), matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9), and provide the experimental data for clinical application of GBE. METHODS: Rats were divided into five groups (n = 20) as following: sham operation group (group A), acute myocardial infarction model group (group B), acute myocardial infarction model + aspirin (10 mg/kg) treatment group (group C), acute myocardial infarction model + captopril (20 mg/kg) treatment group (group D) and acute myocardial infarction model + Ginkgo biloba extract (100 mg/kg) treatment group (group E). The rat acute myocardial infarction model was reproduced by ligaturing the left anterior descending artery excluding the sham operation group which did not ligation only completed the operational process. Each group was further subdivided into treatment regimens lasting 4 weeks and 8 weeks. Immunohistochemistry and real time polymerase chain reaction (PCR) methods were used to detect the protein expression and mRNA transcriptional levels of rat myocardial TGF-beta1, type I collagen, MMP-2 and MMP-9. RESULTS: Compared with group B, regardless of the length of treatment (4 or 8 weeks), the TGF-beta1, MMP-2 and MMP-9 mRNA transcriptional levels, and the protein expression levels of type I collagen, MMP 2 and MMP-9 in groups D, C and E were significantly decreased (P < 0.01). Furthermore, the mRNA expression levels of TGF-beta1 in groups D, C and E were significantly lower after 8 weeks compared to after 4 weeks (P < 0.01), as were the expression levels of type I collagen in groups D, C and E (P < 0.05). There was no statistically significant difference in the protein expression levels of MMP-2 and MMP-9 between groups E and C. CONCLUSIONS: GBE could inhibit experimental rat myocardial remodeling after acute myocardial infarction via reduced transcription of TGF-beta1, MMP-2 and MMP-9 genes and by the decreased expression of type I collagen, MMP-2 and MMP-9 proteins in myocardial cells. PMID- 26268461 TI - Cancer incidence among HIV-positive women in British Columbia, Canada: Heightened risk of virus-related malignancies. AB - OBJECTIVES: We used population-based data to identify incident cancer cases and correlates of cancer among women living with HIV/AIDS in British Columbia (BC), Canada between 1994 and 2008. METHODS: Data were obtained from a retrospective population-based cohort created from linkage of two province-wide databases: (1) the database of the BC Cancer Agency, a province-wide population-based cancer registry, and (2) a database managed by the BC Centre for Excellence in HIV/AIDS, which contains data on all persons treated with antiretroviral therapy in BC. This analysis included women (>= 19 years old) living with HIV in BC, Canada. Incident cancer diagnoses that occurred after highly active antiretroviral therapy (HAART) initiation were included. We obtained a general population comparison of cancer incidence among women from the BC Cancer Agency. Bivariate analysis (Pearson chi(2) , Fisher's exact or Wilcoxon rank-sum test) compared women with and without incident cancer across relevant clinical and sociodemographic variables. Standardized incidence ratios (SIRs) were calculated for selected cancers compared with the general population sample. RESULTS: We identified 2211 women with 12 529 person-years (PY) of follow-up who were at risk of developing cancer after HAART initiation. A total of 77 incident cancers (615/100 000 PY) were identified between 1994 and 2008. HIV-positive women with cancer, in comparison to the general population sample, were more likely to be diagnosed with invasive cervical cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma and Kaposi's sarcoma and less likely to be diagnosed with cancers of the digestive system. CONCLUSIONS: This study observed elevated rates of cancer among HIV-positive women compared to a general population sample. HIV-positive women may have an increased risk for cancers of viral-related pathogenesis. PMID- 26268462 TI - Transpupillary thermotherapy as a primary treatment for circumscribed choroidal haemangioma. PMID- 26268463 TI - Preserved transmembrane protein mobility in polymer-supported lipid bilayers derived from cell membranes. AB - Supported lipid bilayers (SLBs) have contributed invaluable information about the physiochemical properties of cell membranes, but their compositional simplicity often limits the level of knowledge that can be gained about the structure and function of transmembrane proteins in their native environment. Herein, we demonstrate a generic protocol for producing polymer-supported lipid bilayers on glass surfaces that contain essentially all naturally occurring cell-membrane components of a cell line while still retaining transmembrane protein mobility and activity. This was achieved by merging vesicles made from synthetic lipids (PEGylated lipids and POPC lipids) with native cell-membrane vesicles to generate hybrid vesicles which readily rupture into a continuous polymer-supported lipid bilayer. To investigate the properties of these complex hybrid SLBs and particularly the behavior of their integral membrane-proteins, we used total internal reflection fluorescence imaging to study a transmembrane protease, beta secretase 1 (BACE1), whose ectoplasmic and cytoplasmic domains could both be specifically targeted with fluorescent reporters. By selectively probing the two different orientations of BACE1 in the resulting hybrid SLBs, the role of the PEG cushion on transmembrane protein lateral mobility was investigated. The results reveal the necessity of having the PEGylated lipids present during vesicle adsorption to prevent immobilization of transmembrane proteins with protruding domains. The proteolytic activity of BACE1 was unadulterated by the sonication process used to merge the synthetic and native membrane vesicles; importantly it was also conserved in the SLB. The presented strategy could thus serve both fundamental studies of membrane biophysics and the production of surface-based bioanalytical sensor platforms. PMID- 26268464 TI - Erratum: Long-term Hemodialysis Corrects Left Ventricular Dyssynchrony in End stage Renal Disease: A Study with Gated Technetium-99m Sestamibi Myocardial Perfusion Single-photon Emission Computed Tomography. PMID- 26268465 TI - Selective synthesis of single- and multi-walled supramolecular nanotubes by using solvophobic/solvophilic controls: stepwise radial growth via "coil-on-tube" intermediates. AB - Novel hexa-peri-hexabenzocoronene (HBC) derivatives, (F) HBC and (F) HBC*, which carry perfluoroalkyl segments on one side of the HBC core and long alkyl tails on the other, were synthesized. Their perfluoroalkyl segments are highly solvated in C6 F6 (solvophilic effect) and do not assemble, whereas in CH2 Cl2 , they are excluded (solvophobic effect) and assemble together consequently. For example, the use of C6 F6 and CH2 Cl2 as assembling media for (F) HBC leads to the selective formation of single- and multi-walled nanotubes, respectively. When a higher monomer concentration is applied in CH2 Cl2 , multi-walled nanotubes with a larger number of walls result. (F) HBC in CH2 Cl2 self-assembles rather slowly, thereby allowing for the observation of coil-on-tube structures, which are possible intermediates for the stepwise radial growth of the nanotubular wall. Casting of the multi-walled nanotubes onto a quartz plate yields a superhydrophobic thin film with a water contact angle of 161+/-2 degrees . PMID- 26268466 TI - Clinical parameters predicting pathologic complete response following neoadjuvant chemoradiotherapy for rectal cancer. AB - INTRODUCTION: Preoperative chemoradiotherapy (CRT), followed by total mesorectal excision, has become the standard of care for patients with clinical stages II and III rectal cancer. Patients with pathologic complete response (pCR) to preoperative CRT have been reported to have better outcomes than those without pCR. However, the factors that predict the response to neoadjuvant CRT have not been well defined. In this study, we aimed to investigate the impact of clinical parameters on the development of pCR after neoadjuvant chemoradiation for rectal cancer. METHODS: A total of 323 consecutive patients from a single institution who had clinical stage II or III rectal cancer and underwent a long-course neoadjuvant CRT, followed by curative surgery, between 2005 and 2013 were included. Patients were divided into two groups according to their responses to neoadjuvant therapy: the pCR and non-pCR groups. The clinical parameters were analyzed by univariate and multivariate analyses, with pCR as the dependent variable. RESULTS: Of the 323 patients, 75 (23.2%) achieved pCR. The two groups were comparable in terms of age, sex, body mass index, tumor stage, tumor location, tumor differentiation, radiation dose, and chemotherapy regimen. On multivariate analysis, a pretreatment carcinoembryonic antigen (CEA) level of <= 5 ng/mL [odds ratio (OR) = 2.170, 95% confidence interval (CI) = 1.195-3.939, P = 0.011] and an interval of >7 weeks between the completion of chemoradiation and surgical resection (OR = 2.588, 95% CI = 1.484-4.512, P = 0.001) were significantly associated with an increased rate of pCR. CONCLUSIONS: The pretreatment CEA level and neoadjuvant chemoradiotherapy-surgery interval were independent clinical predictors for achieving pCR. These results may help clinicians predict the prognosis of patients and develop adaptive treatment strategies. PMID- 26268468 TI - Shaping up: a geometric morphometric approach to assemblage ecomorphology. AB - This study adopts an ecomorphological approach to test the utility of body shape as a predictor of niche relationships among a stream fish assemblage of the Tickfaw River (Lake Pontchartrain Basin) in southeastern Louisiana, U.S.A. To examine the potential influence of evolutionary constraints, analyses were performed with and without the influence of phylogeny. Fish assemblages were sampled throughout the year, and ecological data (habitat and tropic guild) and body shape (geometric morphometric) data were collected for each fish specimen. Multivariate analyses were performed to examine relationships and differences between body shape and ecological data. Results indicate that a relationship exists between body shape and trophic guild as well as flow regime, but no significant correlation between body shape and substratum was found. Body shape was a reliable indicator of position within assemblage niche space. PMID- 26268467 TI - A novel antigen capture ELISA for the specific detection of IgG antibodies to elephant endotheliotropic herpes virus. AB - BACKGROUND: Elephants are classified as critically endangered animals by the International Union for Conservation of Species (IUCN). Elephant endotheliotropic herpesvirus (EEHV) poses a large threat to breeding programs of captive Asian elephants by causing fatal haemorrhagic disease. EEHV infection is detected by PCR in samples from both clinically ill and asymptomatic elephants with an active infection, whereas latent carriers can be distinguished exclusively via serological assays. To date, identification of latent carriers has been challenging, since there are no serological assays capable of detecting seropositive elephants. RESULTS: Here we describe a novel ELISA that specifically detects EEHV antibodies circulating in Asian elephant plasma/serum. Approximately 80 % of PCR positive elephants display EEHV-specific antibodies. Monitoring three Asian elephant herds from European zoos revealed that the serostatus of elephants within a herd varied from non-detectable to high titers. The antibody titers showed typical herpes-like rise-and-fall patterns in time which occur in all seropositive animals in the herd more or less simultaneously. CONCLUSIONS: This study shows that the developed ELISA is suitable to detect antibodies specific to EEHV. It allows study of EEHV seroprevalence in Asian elephants. Results confirm that EEHV prevalence among Asian elephants (whether captive-born or wild-caught) is high. PMID- 26268469 TI - MicroRNAs and Physical Activity. AB - Micro-RNAs (miRNAs) are responsible for important and evolutionary-conserved regulatory functions in several cellular processes such as apoptosis, signalling, differentiation and proliferation. There is a growing interest in understanding more clearly the mechanisms regulating activation and suppression of miRNAs expression in benefit of health prevention advancement. It is now acknowledged that physical activity represents one of the most effective preventive agents in chronic degenerative diseases. Indeed, a regular exercise exerts a great influence on several parameters and biological pathways, both at genomic and post genomic levels. Recent works have highlighted the effects of structured physical activity on miRNAs modulation. Modulation of MiRNAs, regulated by exercise in human skeletal muscle, depends on type, duration and intensity of an exercise performed. The aim of this review is to provide a comprehensive overview of scientific evidence concerning the effects of physical activity on miRNAs and its relevance for chronic-degenerative diseases prevention. PMID- 26268471 TI - The influence of ionic strength and mixing ratio on the colloidal stability of PDAC/PSS polyelectrolyte complexes. AB - Polyelectrolyte complexes (PECs) form by mixing polycation and polyanion solutions together, and have been explored for a variety of applications. One challenge for PEC processing and application is that under certain conditions the as-formed PECs aggregate and precipitate out of suspension over the course of minutes to days. This aggregation is governed by several factors such as electrostatic repulsion, van der Waals attractions, and hydrophobic interactions. In this work, we explore the boundary between colloidally stable and unstable complexes as it is influenced by polycation/polyanion mixing ratio and ionic strength. The polymers examined are poly(diallyldimethylammonium chloride) (PDAC) and poly(sodium 4-styrenesulfonate) (PSS). Physical properties such as turbidity, hydrodynamic size, and zeta potential are investigated upon complex formation. We also perform detailed molecular dynamics simulations to examine the structure and effective charge distribution of the PECs at varying mixing ratios and salt concentrations to support the experimental findings. The results suggest that the colloidally stable/unstable boundary possibly marks the screening effects from added salt, resulting in weakly charged complexes that aggregate. At higher salt concentrations, the complexes initially form and then gradually dissolve into solution. PMID- 26268470 TI - Osteogenic differentiation and proliferation of bone marrow-derived mesenchymal stromal cells on PDLLA + BMP-2-coated titanium alloy surfaces. AB - RhBMP-2 is clinically applied to enhance bone healing and used in combination with titanium fixation implants. The purpose of this in vitro study was to compare the osteogenic differentiation and proliferation of hMSC on native polished versus sandblasted titanium surfaces (TS) and to test their behavior on pure poly-D,L-lactide (PDLLA) coated as well as PDLLA + rhBMP-2 coated TS. Furthermore, the release kinetics of PDLLA + rhBMP-2-coated TS was investigated. Human bone marrow cells were obtained from three different donors (A: male, 16 yrs; B: male, 27 yrs, C: male, 49 yrs) followed by density gradient centrifugation and flow cytometry with defined antigens. The cells were seeded on native polished and sandblasted TS, PDLLA-coated TS and PDLLA + rhBMP-2-coated TS. Osteogenic differentiation (ALP specific activity via ALP and BCA assay) and proliferation (LDH cytotoxicity assay) was examined on day 7 and 14 and release kinetics of rhBMP-2 was investigated on day 3, 7, 10, and 14. We found significant higher ALP specific activity and LDH activity on native polished compared to native sandblasted surfaces. PDLLA led to decreased ALP specific and LDH activity on both surface finishes. Additional rhBMP-2 slightly diminished this effect. RhBMP-2-release from coated TS decreased nearly exponentially with highest concentrations at the beginning of the cultivation period. The results of this in vitro study suggest that native TS stimulate hMSC significantly stronger toward osteogenic differentiation and proliferation than rhBMP-2 + PDLLA-layered TS in the first 14 days of cultivation. The PDLLA-layer seems to inhibit local hMSC differentiation and proliferation. PMID- 26268472 TI - Cutaneous basal cell carcinosarcoma: case report and literature review. AB - Carcinosarcomas are malignant neoplasms with biphasic carcinomatous and sarcomatous or sarcoma-like components. In general, the sarcomatous component is accepted to be the result of divergent mesenchymal differentiation of the epithelial component. Although well characterized in some anatomic locations (e.g. uterus, upper aerodigestive tract and lung), carcinosarcomas of the skin are rare. Reported epithelial components include squamous, adnexal, neuroendocrine and basaloid. Including this case, only 47 cases of primary cutaneous basal cell carcinosarcoma have been reported in the literature to date. We performed an extensive immunophenotypic evaluation in our case, which confirmed the previously reported coexpression of p53 in both components, and revealed a hitherto unreported coexpression of p16 and p63. Additionally, this report reviews the clinical, pathologic, immunophenotypic characteristics and outcomes of the basal cell carcinosarcomas reported in the literature, in order to emphasize the overall uniform characteristics and clinical behavior of this neoplasm. PMID- 26268473 TI - Inhibition of hepatitis B virus replication by quercetin in human hepatoma cell lines. AB - Hepatitis B virus (HBV) infection is one of the most serious and prevalent viral diseases in the world. Although several anti-HBV drugs have been used clinically, their side and adverse effects limit treatment efficacy. Therefore, it is necessary to identify novel potential anti-HBV agents. The flavonol quercetin has shown activity against some retroviruses, but its effect on HBV remains unclear. In the present study, quercetin was incubated with HepG2.2.15 cells, as well as HuH-7 cells transfected with an HBV plasmid. Quercetin was shown to significantly reduce Hepatitis B surface antigen (HBsAg) and Hepatitis B e antigen (HBeAg), secretion and HBV genomic DNA levels in both cell lines. In addition, co incubation with lamivudine (3TC), entecavir (ETV), or adefovir (Ade) further enhanced the quercetin-induced inhibition of HBV replication. This inhibition was partially associated with decreased heat shock proteins and HBV transcription levels. The results indicate that quercetin inhibited HBV antigen secretion and genome replication in human hepatoma cell lines, which suggests that quercetin may be a potentially effective anti-HBV agent. PMID- 26268474 TI - Predicting risk factors for rebleeding, infections, mortality following peptic ulcer bleeding in patients with cirrhosis and the impact of antibiotics prophylaxis at different clinical stages of the disease. AB - BACKGROUND: Infections in cirrhotic patients with upper gastrointestinal bleeding are a common event causing severe complication and mortality. This study aimed to identify risk factors that may predict rebleeding, bacterial infections, and the impact of antibiotic prophylaxis on mortality at different stages of cirrhosis following acute peptic ulcer bleeding (PUB). METHODS: A hospital-based retrospective cohort study was conducted on 235 cirrhotic patients with acute peptic ulcer hemorrhage who underwent therapeutic endoscopic procedures between January 2008 and January 2014 (n = 235); of these, 88 patients received prophylactic intravenous ceftriaxone (antibiotic group) and 147 patients did not (nil-antibiotic group). The recorded outcomes were length of hospital stay, bacterial infection, rebleeding, and in-hospital mortality. RESULTS: Forty-eight (20.4%) patients experienced ulcer rebleeding and 46 (19.6%) developed bacterial infections. More patients suffered from infection and recurrent bleeding in the nil-antibiotic group than the antibiotic group (25.2% vs. 10.2%, p = 0.005 and 30.6% vs. 3.4%; p < 0.001, respectively). The predictive risk factors for rebleeding were the Rockall score (p = 0.004), units of blood transfusion (p = 0.031), and no antibiotic prophylaxis (p <0.001); for bacterial infections, they were the Child-Pugh score (p = 0.003), active alcoholism (p = 0.035), and no antibiotic prophylaxis (p = 0.009). Overall, 40 (17%) patients died during hospitalization. The Rockall score and rebleeding were predictive factors for in hospital mortality. In subgroup analysis, survival was significantly reduced in decompensated patients (p = 0.034). CONCLUSIONS: This study suggests that antibiotic prophylaxis after endoscopic hemostasis for acute PUB prevented infections and reduced rebleeding events in cirrhotic patients. Antibiotic prophylaxis improved survival among decompensated cohort following PUB. The Rockall score and rebleeding were predictive risk factors for in-hospital mortality. PMID- 26268477 TI - Binge Eating Disorder and Youth. AB - Children and adolescents who eat unusually large amounts of food, feel guilty about it, and try to hide their overeating may be struggling with binge eating disorder (BED), a condition associated with suicidal ideation and other eating disorders. Although BED is new to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, the syndrome is becoming increasingly recognized. The study of BED in children and adolescents is in its natal phase, but the importance of recognition and possible treatment strategies are discussed in the current article along with psychiatric nursing implications. PMID- 26268475 TI - Retinal Vasculature Fractal Dimension Measures Vessel Density. AB - PURPOSE: The goal of this study was to provide the empirical evidence of fractal dimension as an indirect measure of retinal vasculature density. MATERIALS AND METHODS: Two hundred retinal samples of right eye [57.0% females (n = 114) and 43.0% males (n = 86)] were selected from baseline visit. A custom-written software was used for vessel segmentation. Vessel segmentation is the process of transforming two-dimensional color images into binary images (i.e. black and white pixels). The circular area of approximately 2.6 optic disc radii surrounding the center of optic disc was cropped. The non-vessels fragments were removed. FracLac was used to measure the fractal dimension and vessel density of retinal vessels. RESULTS: This study suggested that 14.1% of the region of interest (i.e. approximately 2.6 optic disk radii) comprised retinal vessel structure. Using correlation analysis, vessel density measurement and fractal dimension estimation are linearly and strongly correlated (R = 0.942, R(2) = 0.89, p < 0.001). Polynomial regression model suggests quadratic regression as the best fit for our data (linear: R(2) = 0.1024, 198 d.f., p < 0.001, quadratic: R(2) = 0.1236, 197 d.f., p < 0.001, cubic: R(2) = 0.1236, 196 d.f., p < 0.001). CONCLUSIONS: This study demonstrated the ability of vessel density measurement to detect the changes in the morphology of retinal microvascular associated with increasing age. Thus, vessel density can be suggested to be another parameter in the quantification of retinal microvasculature. PMID- 26268478 TI - Alexithymia: Should This Personality Disorder Be Considered During Treatment of Patients With Mental Illness? AB - Alexithymia is characterized by impairment of an individual's ability to experience, identify, and express emotions, and is associated with impaired emotional intelligence and an externally oriented cognitive style. There has been increasing interest in the phenomenon, with numerous peer-reviewed articles published recently. Alexithymia may occur in patients with many psychiatric disorders, and more severe alexithymia is related to worse outcome. However, many clinicians remain unaware of the issue. The current article discusses alexithymia and its importance in the field of mental health. PMID- 26268479 TI - Improving Awareness of an Acute Psychiatric Unit's Capacity for Admission. AB - New admissions to psychiatric inpatient units can significantly impact the environment and level of safety. Maintaining safety is a core and critical responsibility of nursing, but nurses are often overlooked in the decision to admit a patient. Missed opportunities for dialogue between nurses and the admitting physician challenge nurses' ability to proactively manage the therapeutic environment. When nurses are limited in this ability, the outcome can be an unpredictable and unstable milieu. In a 25-bed acute psychiatric inpatient unit, a formalized communication system among the multidisciplinary admission team was developed. Data collected over 1 year demonstrated improved safety. Increasing the admitting provider's awareness of the current unit acuity and involving the nursing staff early in the admission process improved collaboration among care team members and reduced risks to maintaining milieu safety. PMID- 26268480 TI - Staying Connected: Sustaining Collaborative Care Models with Limited Funding. AB - Providing psychiatric services in the primary care setting is challenging. The multidisciplinary, coordinated approach of collaborative care models (CCMs) addresses these challenges. The purpose of the current article is to discuss the implementation of a CCM at a free medical clinic (FMC) where volunteer staff provide the majority of services. Essential components of CCMs include (a) comprehensive screening and assessment, (b) shared development and communication of care plans among providers and the patient, and (c) care coordination and management. Challenges to implementing and sustaining a CCM at a FMC in Virginia attempting to meet the medical and psychiatric needs of the underserved are addressed. Although the CCM produced favorable outcomes, sustaining the model long-term presented many challenges. Strategies for addressing these challenges are discussed. PMID- 26268481 TI - The debate over digital technology and young people. PMID- 26268482 TI - Comparison of sirolimus eluting stent with bioresorbable polymer to everolimus eluting stent with permanent polymer in bifurcation lesions: Results from CENTURY II trial. AB - OBJECTIVE: To demonstrate the safety and efficacy of a new sirolimus eluting stent with bioresorbable polymer, Ultimaster, (BP-SES) compared with everolimus eluting, permanent polymer, Xience stent (PP-EES) in bifurcation lesions with respect to the freedom from Target Lesion Failure at 1-year. METHODS: Within 1,119 patients enrolled in the CENTURY II randomized controlled multicenter trial, 194 patients were treated for bifurcation lesions and randomized to either BP-SES (n = 95) or PP-EES (n = 99). The primary endpoint was freedom from target lesion failure (TLF) composite endpoint [cardiac death, MI not clearly attributable to a non-target vessel, and clinically driven target lesion revascularization (TLR)] at 1-year. RESULTS: Baseline patient demographic, angiographic, and stenting characteristics were similar in both study arms. A single stent technique with provisional or "cross over" stenting were the most widely used in both arms (93.2% BP-SES vs. 92.4% PP-EES). Freedom from TLF at 1 year was 94.7% for BP-SES and 91.9% for PP-EES (P for noninferiority 0.031). The rate of clinically driven target lesion revascularization (TLR) at 1-year was 3.2% for BP-SES and 3.0% for PP-EES (P = 0.95). There were no significant differences detected in any of the individual clinical endpoints or other secondary clinical endpoints between the study arms at 1-year follow up. CONCLUSIONS: The new bioresorbable polymer sirolimus-eluting stent showed safety and efficacy profiles similar to durable polymer everolimus-eluting in the treatment of patients with bifurcation lesions at 1-year follow up. (c) 2015 Wiley Periodicals, Inc. PMID- 26268484 TI - Bacillus hisashii sp. nov., isolated from the caeca of gnotobiotic mice fed with thermophile-fermented compost. AB - A taxonomic study was performed on 15 bacterial isolates from the caeca of gnotobiotic mice that had been fed with thermophile-fermented compost. The 15 isolates were thermophilic, Gram-stain-positive, facultatively anaerobic, endospore-forming bacteria, and were most closely related to Bacillus thermoamylovorans CNCM I-1378T. The 16S rRNA gene sequence of strain N-11T, selected as representative of this new group, showed a similarity of 99.4 % with Bacillus thermoamylovorans CNCM I-1378T, 94.7 % with Bacillus thermolactis R 6488T, and 94.4 % with Bacillus kokeshiiformis MO-04T. The isolates were then classified into two distinct groups based on a (GTG)5-fingerprint analysis. Two isolates, N-11T and N-21, were the representatives of these two groups, respectively.' The N-11T and N-21 isolates showed 66-71 % DNA-DNA relatedness with one other, but had less than 37 % DNA-DNA relatedness with B. thermoamylovorans LMG 18084T. The other 13 isolates showed DNA-DNA relatedness values above 74 % with the N-11T isolate. All 15 isolates grew at 25-60 degrees C (optimum 50 degrees C), pH 6-8 (optimum pH 7) and were capable of growing on a medium containing 6 % (w/v) NaCl (optimum 0.5 %). The 15 isolates could be distinguished from B. thermoamylovorans LMG 18084T because they showed Tween 80 hydrolysis activity and did not produce acid from melibiose. The major fatty acids were anteiso-C15 : 0, C16 : 0, iso-C15 : 0, iso-C14 : 0 and iso-C16 : 0. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and several unidentified phospholipids. The diagnostic diamino acid in the cell-wall peptidoglycan was meso-diaminopimelic acid. The menaquinone was MK-7. The DNA G+C content was 37.9 mol%. Based on the phenotypic properties, the 15 strains represent a novel species of the genus Bacillus, for which the name Bacillus hisashii sp. nov. is proposed. The type strain is N-11T ( = NRBC 110226T = LMG 28201T). PMID- 26268483 TI - Characterization of a new commercial single crystal diamond detector for photon- and proton-beam dosimetry. AB - A synthetic single crystal diamond detector (SCDD) is commercially available and is characterized for radiation dosimetry in various radiation beams in this study. The characteristics of the commercial SCDD model 60019 (PTW) with 6- and 15-MV photon beams, and 208-MeV proton beams, were investigated and compared with the pre-characterized detectors: Semiflex (model 31010) and PinPoint (model 31006) ionization chambers (PTW), the EDGE diode detector (Sun Nuclear Corp) and the SFD Stereotactic Dosimetry Diode Detector (IBA). To evaluate the effects of the pre-irradiation, the diamond detector, which had not been irradiated on the day, was set up in the water tank, and the response to 100 MU was measured every 20 s. The depth-dose and profiles data were collected for various field sizes and depths. For all radiation types and field sizes, the depth-dose data of the diamond chamber showed identical curves to those of the ionization chambers. The profile of the diamond detector was very similar to those of the EDGE and SFD detectors, although the Semiflex and PinPoint chambers showed volume-averaging effects in the penumbrae region. The temperature dependency was within 0.7% in the range of 4-41 degrees C. A dose of 900 cGy and 1200 cGy was needed to stabilize the chamber to the level within 0.5% and 0.2%, respectively. The PTW type 60019 SCDD detector showed suitable characteristics for radiation dosimetry, for relative dose, depth-dose and profile measurements for a wide range of field sizes. However, at least 1000 cGy of pre-irradiation will be needed for accurate measurements. PMID- 26268485 TI - Characteristics of subthalamic oscillatory activity in parkinsonian akinetic rigid type and mixed type. AB - OBJECTIVE: To explore neurons with beta oscillatory activity in the subthalamic nucleus (STN) in relation to parkinsonian motor signs. METHODS: We studied 27 patients with Parkinson's disease (PD) who underwent electrode implantation for STN deep brain stimulation. Thirteen patients were classified as akinetic-rigid (AR) type and 14 patients were classified as mixed type. Microelectrode recording was performed in the STN and the electromyogram (EMG) was simultaneously recorded. Single-unit and spectral analyses were performed. Coherence analysis was used to explore the relationship between beta oscillatory activity and EMG activity. Unpaired t-test and chi-square were used to compare the differences between the two PD types. RESULTS: Of 130 neurons identified in the AR type, 43.8% were beta oscillatory neurons (mean: 21.3 +/- 6.87 Hz, betaFB) and 0.8% were tremor frequency oscillatory neurons (4-6 Hz, TFB). Of 102 neurons identified in the mixed type, 19.6% were beta oscillatory neurons and 26.5% were TFB oscillatory neurons. There was a significant difference in proportion of neurons with betaFB and TFB oscillations between the two PD groups. Additionally, 12% of the betaFB oscillatory neurons were coherent with limb EMG of the AR type, but there was no coherence in the mixed type. Most oscillatory neurons were localized in the dorsal portion of the STN. CONCLUSION: The STN betaFB oscillatory neurons correlate with parkinsonian rigidity-bradykinesia. The high proportion of betaFB oscillatory neurons found in the AR type of PD is indirect evidence for their importance in generating motor impairment. PMID- 26268487 TI - [Progresses and challenges for basic and clinical researches on congenital external and middle ear malformations]. PMID- 26268486 TI - Environmental Health and Safety Hazards Experienced by Home Health Care Providers: A Room-by-Room Analysis. AB - The number of personnel providing in-home health care services is increasing substantially. The unique configuration of environmental hazards in individual client homes has a significant impact on the safety and health of home health care providers (HHPs). This mixed-methods study used data from a standardized questionnaire, focus groups, and individual interviews to explore environmental health and safety hazards encountered by HHPs in client homes. The participant sample (N = 68) included nurses, aides, therapists, and owners/managers from a variety of geographic locations. The most often-reported hazards were trip/slip/lift hazards, biohazards, and hazards from poor air quality, allergens, pests and rodents, and fire and burns. Frequency of identified key hazards varied by room, that is, kitchen (e.g., throw rugs, water on floor), bathroom (e.g., tight spaces for client handling), bedroom (e.g., bed too low), living room (e.g., animal waste), and hallway (e.g., clutter). Findings indicate the need for broader training to enable HHPs to identify and address hazards they encounter in client homes. PMID- 26268488 TI - [Expert consensus on treatment for congenital malformation of external and middle ear]. PMID- 26268489 TI - [Ear reconstruction: from reconstructive to cosmetic]. AB - OBJECTIVE: Previous literatures have reported favorable results in ear reconstruction. Many details in fabricating cartilage framework have been paid much attention. Whereas, many patients still complain about unnatural contours. This article is to provide a new technique to solve some of the problems. METHODS: A total of 253 patients underwent reconstruction using the modified technique from 2011 to 2014. In fabricating the complex of antihelix, the authors modified the prior method. Instead of sculpting a sharp Y-shaped cartilage graft for projecting the prominent structures, the authors increased the width of the superior crura, sculpted a gentle slope in the both sides of superior crura, simultaneously carved a groove in the base frame to join with the carved attachment smoothly. The width of inferior crura was about one third of the superior crura width, and the inferior crura was narrow and prominent. A gentle slope was carved on the antihelix and a groove was carved on the base frame for the antihelix to sit on. RESULTS: Four cases have been selected to illustrate the favorable results of this technique. Due to the modified details, the superior crura, inferior crura, antihelix and the structures around them, in these cases, show natural contours, and provide a coordinated figure to the integrity of reconstructed ear. CONCLUSIONS: Antihelix complex is one of the most important structures for creating a natural auricle. The natural superior and inferior crura and antihelix can enhance the impression of a harmonious shape, and acquire an increased satisfaction for both patients and surgeons. PMID- 26268490 TI - [Selection and application of ear reconstruction surgery for Chinese microtia]. AB - OBJECTIVE: Based on the different physiological characteristics of the mastoid skin and soft tissue of Chinese congenital microtia malformation, the Nagata two stage method was respectively applied for ear reconstruction, and the clinic experience were investigated in this study. METHOD: According to the mastoid skin and soft tissue difference in the thickness and tightness, 280 patients diagnosed with congenital microtia were divided into four types: thin and tight, thin and loose, thick and tight, thick and loose type. 90 cases of thin and loose type accepted the Nagata method of ear reconstruction surgery. RESULTS: With average 7.8 months follow up, 84.4% (76/90) cases using Nagata two-stage method were satisfied with the outcome of the reconstructed ear including three dimensional position and subunit appearance. There were no postoperative complication related to chest wall deformity or affected normal physical function. CONCLUSIONS: The Nagata two-stage method is appropriate management choice for Chinese congenital microtia. Based on the different physiological characteristics of the mastoid skin and soft tissue, the selection of different operational should be beneficial to the ear reconstruction of Chinese congenital microtia malformation. PMID- 26268491 TI - [Three-stage surgery of combining auricle reconstruction, meatoplasty and tympanoplasty for patients with congenital microtia-atresia]. AB - OBJECTIVE: To investigate the validity and feasibility of consecutive three-stage surgical technique of combining auricle reconstruction with external auditory canal atresia reconstruction in patients with congenital microtia-atresia, and to assess the post-surgery results by cosmetic and hearing aspects. METHODS: From Sep. 2007 to Jun. 2011, all 74 patients (79 ears) with congenital microtia atresia treated in our department were enrolled in this study. They consecutively accepted the following three-stage surgical technique: The first stage was Brent' s technique as follows, rib cartilage graft harvest, framework fabrication, and implantation. The second stage combined transfer of the lobule with meatoplasty and tympanoplasty. The third stage was the elevation of the reconstructed auricle. Both the cosmetic and functional hearing results were recorded at follow ups. RESULTS: Among these patients, 60 patients (78.5%), 62 ears, acquired extremely satisfactory cosmetic results; 10 patients (16.5%), 13 ears, acquired acceptable cosmetic results; while the remaining 4 patients (5.1%) acquired unsatisfactory cosmetic results. However, the height of elevation of the newly performed auricle framework was not enough due to the existence of newly formed external ear canal. Regarding the hearing results, there were 69 ears with followup audiograms. An air-bone gap (ABG) improvement of 12.5 dB was achieved. The air-conduction hearing threshold improved (10.9 +/- 8.2) dBHL, 37 ears (53.6%) achieved serviceable hearing after surgery, with ABG less than 30 dB. There were multiple complications occurred after surgery with the incidence of 49.4% (39/79). CONCLUSIONS: The combined three-stage surgical microtia and canal atresia reconstruction technique is a viable choice for some suitable patients with microtia-atresia. However, the incidence of complication after meatoplasty is very high and the hearing restoration is not good enough, which need further investigation for the better results. PMID- 26268492 TI - [Self-rated efficacy in bilateral aural atresia patients using bone-anchored hearing aid]. AB - OBJECTIVE: Using questionnaires to evaluate the audiological benefit and satisfaction of bilateral aural atresia patients with bone-anchored hearing aid (Baha). METHODS: Implanted Baha user questionnaire was applied to 19 patients suffering bilateral aural atresia, and 15 of the patients were evaluated with abbreviated profile of hearing aid benefit (APHAB). Glasgow children's benefit inventory (GCBI) was used to measure subjective benefit of patients under the age of 18. RESULTS: The Baha user questionnaire demonstrated great satisfaction. The mean Baha scores for the subdomains of ease of communication (EC), backgroud noise (BN) and revereration (RV) were decreased by 54.6 +/- 10.2 (t = 20.6, P < 0.05), 46.9 +/- 11.1 (t = 16.4, P < 0.05) and 58.8 +/-15.4 (t = 21.4, P < 0.05) compared to the unaided scores. For the subdomain of aversiveness (AV), the Baha score was 56.7 +/- 9.9 (t = 10.8, P < 0.05) higher than the unaided score. The general benefit score GCBI was 41.1 +/- 13.0. CONCLUSION: Baha can significantly improve hearing ability and quality of life of patients with bilateral aural atresia. PMID- 26268493 TI - [Prevalence and psychopathological characteristics of anxiety and depression in patients with chronic rhinosinusitis before endoscopic sinus surgery]. AB - OBJECTIVE: To investigate the prevalence and psychopathological characteristics of anxiety and depression in patients with chronic rhinosinusitis (CRS) and to find the risk factors leading to psychological problems. METHODS: Between August 2013 and April 2014, 117 consecutive patients with the diagnosis of CRS who had been scheduled for endoscopic sinus surgery were prospectively enrolled. Somatic and psychological symptoms were evaluated using a series of questionnaire instruments. The instruments included symptom checklist-90 (SCL-90), self-rating depression scale (SDS), self-rating anxiety scale (SAS) and the visual analogue scale (VAS) and the sinonasal outcome test 20 (SNOT-20) and Lund-Mackay computed tomography score. The results of SAS, SDS, SCL-90 were compared with the standard, obtained from healthy Chinese population. Multivariate Logistic regression was used to analyze the factors that might cause anxiety and depression. SPSS 19.0 software was used to analyze the data. RESULTS: The scores of SAS and SDS (39.40 +/- 11.55, 54.05 +/- 10.96) were significantly higher than those of our country's normal standard (29.78 +/- 10.46, 41.88 +/- 10.57, t equals 5.648, 7.529, all P < 0.01). The SCL-90 scores were significantly higher than those of the normal standard population, including dimension of somatization, anxiety, depression, psychosis and total average score of the factors ( all P < 0.01), the result of somatization, anxiety, depression had positive correlation with the scores of SAS and SDS (r equals 0.681, 0.781, 0.531, 0.866, 0.674, 0.557, all P < 0.05). Multivariate Logistic regression showed that gender and CRS complicated with asthma or allergic rhinitis (AR) and the symptom of nasal obstruction were related to the incidence of anxiety depression comorbid. In addition, the gender and concurrent asthma had positive correlation with incidence of any anxiety or depressive disorder. To compare the abnormal psychological state group and healthy group, the SNOT-20 scores had no statistical significance (all P > 0.05). CONCLUSIONS: High prevalence of anxiety and depression was found in CRS patients. Such factors as gender, nasal obstruction and concurrent with asthma or AR are high risk factors for anxiety and depression in patients with CRS. PMID- 26268494 TI - [Clinical research on micro-movement sensitive mattress sleep monitoring system in children with obstructive sleep apnea hypopnea syndrome]. AB - OBJECTIVE: To evaluate the diagnostic value of micro-movement sensitive mattress sleep monitoring system (MSMSMS) in children with obstructive sleep apnea hypopnea syndrome. METHODS: Sixty-five children with the complaint of sleep disorder were collected and detected by polysomnography and micro-sensitive mattress sleep monitoring system overnight at least seven hours. The date from two instruments were analyzed by computer automatically and then modified by two professional staff double-blind separately. The data about the diagnosis of sleep breath disorder and other sleep physiology information were compared between the two groups. RESULTS: Sixty-one cases finished the study finally. The mean age of these children was (7.0 +/- 2.7) and the youngest was 3 years old, maximum was 13 years old, male children 46 cases, female patients 15 cases, body mass index (BMI) median [25 quantile; 75 quantile] 16.00 [14.80;17.5]kg/m2. Mean PSG measured apnea hypopnea index (AHI) was 4.50 [2.30;10.15] times/h, and mean MSMSMS AHI was 3.63 [2.56; 6.43] times/h. There was a significant correlation between PSG AHI and AHI by MSMSMS (r = 0.935, P < 0.01). A Bland-Altamplot of PSG AHI and MSMSMS AHI was also used to assess the accuracy of MSMSMS. 95. 1% of the data was fallen in the 95% consistency areas. For AHI--5 times/h and nighttime minimum oxygen < 91% or obstructive apnea index( OAT) > 1 time/h and nighttime minimum oxygen saturation < 91 % as threshold value, the MSMSMS diagnosing sensitivity and specificity were 82.9% and 92.3%. The misdiagnosis rate and missed diagnosis rate were 7.7% and 17.1%. CONCLUSIONS: The MSMSMS offer a simple and comfortable method to monitor children's sleep. It improves the compliance in the process of sleep monitoring. Besides, as a diagnostic tool in the diagnosis of OSAHS on children has a high credibility in AHI. PMID- 26268495 TI - [Continuous positive airway pressure treatment for functional cardiac arrhythmias combined with obstructive sleep apnea hypopnea syndrome]. AB - OBJECTIVE: To discuss the effect of continuous positive airway pressure (CPAP) treatment for functional cardiac arrhythmias combined with obstructive sleep apnea hypopnea syndrome. METHODS: Fifty-six OSAHS patients combined functional cardiac arrhythmia were randomized divided into two groups. The 28 patients in the control group were treated with metoprolol according to cardiac guidelines, the other 28 cases in the experimental group were treated with CPAP therapy combined with metoprolol. AHI and the lowest oxygen saturation (LSaO2) were tested before and after treatment. RESULTS: The efficiency rates were 57.1% and 17.9% in experimental and control group respectively, with statistical difference (chi2 = 7.62, P < 0.01). Total effective rates were 85.7% and 53.6% respectively, with statistical difference (chi2 = 5.41, P < 0.05). In the experimental group, there were three treatment subgroups. After treatment, AHI and the lowest oxygen saturation were significantly different (P < 0.05). CONCLUSION: CPAP treatment can effectively eliminate respiratory disturbance index, improve the symptoms of hypooxygen at night, and effectively improve the therapeutic effect of functional cardiac arrhythmias in OSAHS patients combined with functional arrhythmia. PMID- 26268496 TI - [Clinical application of the combined radical operation without breaking lower lip and mandible for tongue and lingual root carcinoma]. AB - OBJECTIVE: To investigate the clinical applicability and outcomes of the combined radical operation without breaking the lower lip and mandible with one-stage reconstruction using free anterolateral thigh flap for tongue and lingual root carcinoma. METHODS: The operation with or without breaking lower lip and mandible was performed respectively in 245 patients (experimental group) and 120 patients (control group). RESULTS: Removal of tumor and neck dissection were conducted successfully in all patients of two groups with no serious postoperative complication. With the follows-up of 6 to 36 months, in the patients of experimental group there was no recurrence for primary sites but 3 cases with neck lymphnode recurrence, the functions of chewing, swallowing and speaking were good, there was no damage to appearance, and no osteoradionecrosis occurred in the lymphnode positive cases after radiotherapy; in the patients of experimental group there was no recurrence for primary sites but 4 cases with neck lymphnode recurrence, the functions of chewing, swallowing and speaking were good, but there was apparent scar in neck and face, and osteoradionecrosis occurred in 11 of lymphnode positive cases. CONCLUSIONS: The combined radical operation without breaking the lower lip and mandible with one-stage reconstruction using free anterolateral thigh flap is feasible for tongue and lingual root carcinoma (T2 T3), which reduces the risk for osteoradionecrosis in lymphnode positive cases after radiotherapy and keeps good appearance for patients. PMID- 26268497 TI - [Expressions of IL-13 and IL-13Ralpha2 in eosinophilic chronic rhinosinusitis with nasal polyps and clinical implications]. AB - OBJECTIVE: To evaluate the expressions of interleukin (IL) 13 and its receptor IL 13Ralpha2 in eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) and non-ECRSwNP and their clinicopathological implications. METHODS: A total of 60 consecutive patients with CRSwNP who underwent endoscopic sinus surgery (ESS) were divided into two groups of ECRSwNP (n = 27) and non-ECRSwNP (n = 33) based on tissue eosinophil count (more than five cells per high power field) with postoperative pathological examination. Before ESS,the severities of symptoms, nasal polyps, and sinonasal diseases on CT were scored, peripheral blood eosinophil count and percentage, and total serum. IgE level were measured. IL-13 and IL-13Ralpha2 expressions in polyp tissues were examined with immunohistochemistry. SPSS 16.0 software was used to analyze the data. RESULTS: There was no significant differences between ECRSwNP and non-ECRSwNP groups in the mean symptom scores (t = 0.102, P > 0.05), but ECRSwNP, compared to non- ECRSwNP, demonstrated a higher incidence of bilateral polyps (chi2 = 15.879, P < 0.01), a higher mean score of nasal polyps (3.6 +/- 1.1 vs 2.1 +/- 0.8, t = 4.009, P < 0.01) or diseases on CT (t = 4.428, P < 0.01). And also a significant difference existed between two groups in mean blood eosinophil count (t = 3.148, P < 0.01) or percentage (t =3.038, P < 0.01), but no significant difference in total serum levels of IgE (t = 0.659, P > 0.05). There was a closed correlation between tissue eosinophil count and blood eosinophil count (r = 0.683, P < 0.01) or percentage (r = 0.631, P < 0.01) in ECRSwNP, but not in non-ECRSwNP. The expressions of both IL-13 and IL-13Ralpha2 increased significantly in ECRSwNP compared to non-ECRSwNP ( scores 8.1 +/- 1.6 vs. 5.4 +/- 1.6; 8.8 +/- 1.4 vs. 4.8 +/- 1.6, t value was 4.749, 8.010, P < 0.01). CONCLUSIONS: IL-13 and IL-13Ralpha2 are associated closely with pathogenesis o ECRSwNP. Subtyping CRSwNP and studying underly mechanism can be helpful to make treatment strategy for CRSwNP. PMID- 26268498 TI - [The relationship between human papillomavirus and prognosis of oropharyngeal squamous cell carcinoma: a meta analysis]. AB - OBJECTIVE To examine survival differences in prognosis and survival between patients with HPV-positive and those with HPV-negative oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Pubmed, Embase, Web of science and Medline databases were searched from their inception till June 2014. A random-effect meta analysis was used to pool study estimates evaluating overall (all-cause mortality), disease-specific (death from OPSCC), disease-free (recurrence free), progression-free survival outcomes and local regional control rate in HPV positive vs HPV-negative OPSCC. After study selection, two reviewers assessed and extracted data independently. Meta-analysis was performed using the STATA 11.0 software. RESULTS: Thirty-seven studies were included. HPV-positive OPSCC patients had a better overall survival compared to HPV-negative patients (HR 0.39, 95% CI 0.32-0.46). HPV-positive OPSCC patients had a significantly lower disease specific mortality (HR 0.31, 95% CI 0.22-0.39) and were less likely to experience progression or recurrence of their cancers than HPV-negative patients (HR 0.34, 95% CI 0.25-0.42). Both disease-free survival and progression-free survival were significantly improved in patients with HPV-positive OPSCC ( HR 0.38, 95% CI 0.29-0.47 and HR 0.46, 95% CI 0.29-0.63, respectively). CONCLUSIONS: HPV infection is an important prognostic factor of OPSCC. Stratified therapies can be applied in OPSCC based on HPV status of tumours. PMID- 26268499 TI - [Middle ear cholesteatoma with Mouret abscess--a case report]. PMID- 26268500 TI - [Tow cases of septum fungal infection after functional endoscopic sinus surgery]. PMID- 26268501 TI - [Three cases report of primary quamous cell carcinoma of the uvula]. PMID- 26268502 TI - [Chylous fistula in patients with differentiated thyroid carcinoma undergoing thyroidectomy plus central neck dissection]. PMID- 26268503 TI - [A case report of combinational odontoma in nasal cavity]. PMID- 26268504 TI - [Low-grade myofibroblastic sarcoma of the parapharyngeal space: a case report]. PMID- 26268505 TI - [Minutes of the 2014 China Rhinology Annual Meeting]. PMID- 26268506 TI - [Reconstruction for partial auricular defect]. PMID- 26268507 TI - [Neuroendocrine carcinoma of head and neck]. PMID- 26268508 TI - The prevalence and characteristics of obstructive sleep apnea in hospitalized patients with type 2 diabetes in China. AB - Data on the prevalence of obstructive sleep apnea in subjects with type 2 diabetes mellitus in China is scarce. We conducted a multi-centre, cross sectional study involving 12 hospitals from six regional cities to investigate the prevalence of obstructive sleep apnea in hospitalized patients with type 2 diabetes mellitus and to explore the association between obstructive sleep apnea and related risk factors, diabetic complications and comorbidities in China. Each hospital recruited at least 70 consecutive patients with type 2 diabetes mellitus who were admitted to the endocrinology ward. A total of 880 participants were enrolled and administered overnight sleep monitoring with a portable monitor (ApneaLinkTM, ResMed, San Diego, CA, USA); other information was collected from medical charts and a standardized questionnaire. In this study, 60.0% (95% confidence interval: 56.8%, 63.2%) of hospitalized patients in China with type 2 diabetes mellitus had comorbid obstructive sleep apnea (apnea-hypopnea index >= 5). Only 1.5% (eight of 528) of the patients with both conditions had been diagnosed previously with obstructive sleep apnea. The prevalence of moderate severe (apnea-hypopnea index >= 15) and severe obstructive sleep apnea (apnea hypopnea index >= 30) was estimated to be 25.6% (22.7, 28.5%) and 10.3% (8.3, 12.4%), respectively. Age, sex, body mass index, snoring, reported breath-holding in sleep or gasping or choking arousal, sleepiness, diabetes duration, hypertension, diabetic nephropathy and cardiovascular diseases history were correlated significantly with the severity of obstructive sleep apnea. In China, the prevalence of obstructive sleep apnea in hospitalized patients with type 2 diabetes mellitus is high. Routine screening for and treatment of obstructive sleep apnea is an important, but often neglected, part of the management of diabetes. PMID- 26268509 TI - Living Donor Kidney Transplantation: Improving Efficiencies in Live Kidney Donor Evaluation--Recommendations from a Consensus Conference. AB - The education, evaluation, and support of living donors before, during, and after donation have historically been considered the roles and responsibilities of transplant programs. Although intended to protect donors, ensure true informed consent, and prevent coercion, this structure often leaves referring nephrologists unclear about the donor process and uncertain regarding the ultimate outcome of potential donors for their patients. The aim of this article is to help the referring nephrologist understand the donor referral and evaluation process, help the referring nephrologist understand the responsibilities of the transplant program, and offer suggestions about how the referring nephrologist can help to improve efficiencies in the process of donor education and evaluation. A partnership between referring nephrologists and transplant programs is an important step in advancing living kidney donation. The referring nephrologists are the frontline providers and are in a unique position to offer education about living donation and improve efficiencies in the process. Understanding the donor referral and evaluation process, the responsibilities of the transplant program, and the potential role referring nephrologists can play in the process is critical to establishing such a partnership. PMID- 26268510 TI - Meeting sexual partners online: associated sexual behaviour and prevalent chlamydia infection among adolescents in Norway: a cross-sectional study. AB - OBJECTIVES: Evidence is mixed as to whether meeting sexual partners online ('internet-partners') is associated with risky sexual behaviour and/or sexually transmitted infection transmission. Accordingly, we sought to estimate the prevalence of reporting various online romantic and sexual activities among Norwegian adolescents, including internet-partners, and the reason for meeting them and to examine differences in sexual behaviour, partnership characteristics and chlamydia infection prevalence among those reporting internet-partners versus those reporting only offline partners. METHODS: Population-based cross-sectional survey among sexually experienced girls and boys, 15-20 years, using electronic questionnaires and collecting urine samples for Chlamydia trachomatis PCR testing (79% provided both, n=1023). We used logistic regression to examine associations, adjusting for potentially confounding variables. RESULTS: Overall, 30% of both genders reported internet-partners (ever). Boys (but not girls) with internet partners had higher chlamydia prevalence than those reporting meeting sexual partners only offline (8.1%, 95% CI 4.3% to 13.7% vs 1.6%, 0.5% to 3.7%). Two thirds of girls and 37% of boys reported meeting their most recent internet partner to start a romantic relationship, while the remainder did so with the specific intention of having sex. Among both genders, reporting sexual (vs romantic) reasons for meeting their most recent internet-partners was associated with reporting several risky sexual behaviours, including multiple recent sex partners (adjusted OR girls: 3.27, boys: 2.48) and three-fold higher chlamydia prevalence. CONCLUSIONS: This population-based study suggests that internet partners are common among adolescents in Norway, and the reason for meeting them was more strongly associated with additionally reporting sexual risk behaviours and prevalent chlamydia infection than the internet itself as a meeting venue. PMID- 26268511 TI - Are family physicians comprehensively using electronic medical records such that the data can be used for secondary purposes? A Canadian perspective. AB - BACKGROUND: With the introduction and implementation of a variety of government programs and policies to encourage adoption of electronic medical records (EMRs), EMRs are being increasingly adopted in North America. We sought to evaluate the completeness of a variety of EMR fields to determine if family physicians were comprehensively using their EMRs and the suitability of use of the data for secondary purposes in Ontario, Canada. METHODS: We examined EMR data from a convenience sample of family physicians distributed throughout Ontario within the Electronic Medical Record Administrative data Linked Database (EMRALD) as extracted in the summer of 2012. We identified all physicians with at least one year of EMR use. Measures were developed and rates of physician documentation of clinical encounters, electronic prescriptions, laboratory tests, blood pressure and weight, referrals, consultation letters, and all fields in the cumulative patient profile were calculated as a function of physician and patient time since starting on the EMR. RESULTS: Of the 167 physicians with at least one year of EMR use, we identified 186,237 patients. Overall, the fields with the highest level of completeness were for visit documentations and prescriptions (>70%). Improvements were observed with increasing trends of completeness overtime for almost all EMR fields according to increasing physician time on EMR. Assessment of the influence of patient time on EMR demonstrated an increasing likelihood of the population of EMR fields overtime, with the largest improvements occurring between the first and second years. CONCLUSIONS: All of the data fields examined appear to be reasonably complete within the first year of adoption with the biggest increase occurring the first to second year. Using all of the basic functions of the EMR appears to be occurring in the current environment of EMR adoption in Ontario. Thus the data appears to be suitable for secondary use. PMID- 26268512 TI - Mediation effect of recent loss events on weight gain in obese people who experienced childhood parental death or separation. AB - Adverse events during childhood, including loss of a parent, are related to a higher risk of adult obesity. We investigated whether childhood parental loss is related to adult rapid weight gain through exposition to a later loss event. We assessed the mediation effect of recent loss and non-loss events on the association between childhood loss and rapid weight gain in 138 individuals seeking bariatric surgery. Our results showed that recent loss events mediate the effect of childhood parental loss on rapid weight gain (0.790; p < .001), suggesting the need for specific programs to prevent and treat obesity in individuals with multiple losses. PMID- 26268513 TI - Fibroblastic connective tissue nevus. AB - Fibroblastic connective tissue nevus (FCTN) is a newly recognized, benign cutaneous mesenchymal lesion of fibroblasts/myofibroblastic lineage, which expands the classification of connective tissue nevi. We present three cases of FCTN and discuss significant clinical, morphologic and immunophenotypic overlap with dermatomyofibroma. Our cases were from young women, aged 32, 24 and 10, and presented as 1.2 and 1 cm nodules on the posterior neck and right upper flank, respectively while presenting as a linear plaque of the right posterior thigh in the latter case. The lesions showed a poorly circumscribed proliferation of hypercellular spindle cells arranged in short to longer intersecting fascicles entrapping adnexal structures. Superficial adipose tissue was also entrapped in one case. The spindle cells had fibroblastic features with pale eosinophilic cytoplasmic extensions and inconspicuous nucleoli. The spindle cells were positive for CD34 in two cases. One case was negative for CD34, smooth muscle actin (SMA), desmin and S100. The overall features were consistent with a diagnosis of FCTN. In two cases, we further elucidated the fibroblastic differentiation of the spindle cells in FCTN with electron microscopy, which has not been previously described. PMID- 26268515 TI - Evaluation of serum and urine fetuin-A levels in children with acute lymphoblastic leukemia during and after high-dose methotrexate therapy: Relation to toxicity. AB - BACKGROUND/OBJECTIVES: Fetuin-A is a multifunctional protein with its urine level was considered as a marker of acute kidney injury. We investigated the serum and urine fetuin-A in acute lymphoblastic leukemia (ALL) children during and after high-dose methotrexate (HDMTX). METHODS: Twenty-two ALL children and 20 matched healthy controls were included. Liver transaminases, serum creatinine, estimated glomular filtration rate (eGFR), creatinine clearance (CrCl), serum beta2 microglobulin (B2M), and serum and urine fetuin-A levels were assayed pre and 4 months after the consolidation. Among a subgroup of 15 patients, the investigations were performed 42 hours after the start of the second and the fourth HDMTX infusions. RESULTS: HDMTX was well tolerated. During HDMTX, there was significant decline in serum fetuin-A together with significant rise of urine fetuin-A and B2M levels compared to the control and to the pre-consolidation levels, changes that persisted 4 months after the consolidation despite recovery of the significantly altered renal functions. The second HDMTX-related serum fetuin-A level directly correlated with eGFR and CrCl (r = 0.86, P < 0.0001 and r = 0.67, P = 0.016, respectively). Four months after consolidation, urine fetuin-A directly correlated with serum creatinine (r = 0.54, P = 0.004) and inversely correlated with the eGFR (r = -0.66, P < 0.0001). CONCLUSION: Significant disturbance in serum and urinary fetuin-A levels, which was related to renal functions, had occurred during HDMTX and persisted for at least 4 months after the consolidation. Serum and urine fetuin-A could be sensitive markers for subtle renal dysfunction in ALL children. PMID- 26268514 TI - Effects of carnitine on oxidative stress response to intravenous iron administration to patients with CKD: impact of haptoglobin phenotype. AB - BACKGROUND: Anemia is a common disorder in CKD patients. It is largely attributed to decreased erythropoietin (EPO) production and iron deficiency. Therefore, besides EPO, therapy includes iron replenishment. However, the latter induces oxidative stress. Haptoglobin (Hp) protein is the main line of defense against the oxidative effects of Hemoglobin/Iron. There are 3 genotypes: 1-1, 2-1 and 2 2. Hp 2-2 protein is inferior to Hp 1-1 as antioxidant. So far, there is no evidence whether haptoglobin phenotype affects iron-induced oxidative stress in CKD patients. Therefore, the present study examines the influence of carnitine treatment on the intravenous iron administration (IVIR)-induced oxidative stress in CKD patients, and whether Hp phenotype affects this response. METHODS: TRIAL REGISTRATION: Current Controlled Trials ISRCTN5700858. This study included 26 anemic (Hb = 10.23 +/- 0.28) CKD patients (stages 3-4) that were given a weekly IVIR (Sodium ferric gluconate, [125 mg/100 ml] for 8 weeks, and during weeks 5-8 also received Carnitine (20 mg/kg, IV) prior to IVIR. Weekly blood samples were drawn before and after each IVIR for Hp phenotype, C-reactive protein (CRP), advanced oxidative protein products (AOPP), neutrophil gelatinase-associated lipocalin (NGAL), besides complete blood count and biochemical analyses. RESULTS: Eight percent of CKD patients were Hp1-1, 19 % Hp2-1, and 73 % Hp2-2. IVIR for 4 weeks did not increase hemoglobin levels, yet worsened the oxidative burden as was evident by elevated plasma levels of AOPP. The highest increase in AOPP was observed in Hp2-2 patients. Simultaneous administration of Carnitine with IVIR abolished the IVIR-induced oxidative stress as evident by preventing the elevations in AOPP and NGAL, preferentially in patients with Hp2-2 phenotype. CONCLUSIONS: This study demonstrates that Hp2-2 is a significant risk factor for IVIR-induced oxidative stress in CKD patients. Our finding, that co administration of Carnitine with IVIR preferentially attenuates the adverse consequences of IVIR, suggests a role for Carnitine therapy in these patients. PMID- 26268516 TI - Knowledge for Healthcare: the future of health librarianship. AB - Many people are still not receiving the right care. It is imperative for health care librarians to come together around a common vision to achieve Knowledge for Healthcare so that the right knowledge and evidence is used at the right time in the right place. The authors describe five workstreams within a modernisation programme: Service Transformation, Workforce Planning and Development, Quality and Impact, Resource Discovery and Optimising Investment. Communications, engagement and partnership working are central to success. The development framework sets out principles on which to base decisions, and design criteria for transforming services. PMID- 26268517 TI - Predictors of the authenticity of Internet health rumours. AB - BACKGROUND: The Internet is becoming an important source of health information; however, unverified health rumours may be included in health-related search results. There is a critical need to provide health information seekers with methods that are specifically geared towards the identification of the authenticity of health rumours. METHODS: Using 453 health rumours collected from a definitive online reference of rumours in China, this study investigates which features contribute to distinguishing between true and false rumours with a logistic regression model. RESULTS: There are measurable differences between true and false health rumours on the Internet. The lengths of rumour headlines and statements and the presence of pictures are negatively correlated to the probability that a rumour is true, whereas a rumour is more likely to be true if it contains elements such as numbers, source cues and hyperlinks. Finally, dread health rumours are more likely to be true than wish ones. CONCLUSIONS: Despite the growing number of studies on rumours, the identification of the authenticity of rumours has received little attention. This study proposes some rules of thumb to help online users ascertain rumour veracity and make decisions. PMID- 26268518 TI - A case study of the organisation of research knowledge by systematic reviews within the mental health care field. AB - BACKGROUND: Our aim was to explore how systematic reviews of the effects of complex interventions within the field of organisation of mental health care organised research knowledge. METHODS: We looked up references included in 14 mental health care reviews in the database Epistemonikos to examine overlap between reviews. We classified topic concordance between study reports and reviews as similar, narrower, broader or other topic to indicate how well the research knowledge was organised. FINDINGS: We examined 182 comparisons between the theme of study reports and reviews. In 100 (55%) of the 182 comparisons, the review had a broader theme, 18 (10%) narrower, 34 (19%) similar and in 30 (16%), the review's theme was classified as 'other'. The content analysis indicated that there existed (inconsistent) overlapping of study reports between different topics. CONCLUSIONS: Within the field organisation of mental health care, there exists some unclear and inconsistent organisation of current knowledge. This may diminish the validity and reliability of systematic reviews. It is important that review authors take care in defining the review question precisely, conduct thorough literature searches, consider each study's hypothesis, disciplinary tradition and context, and if necessary, examine which other reviews have included a study in question. PMID- 26268519 TI - The story so far: a summary of the contributions to the 'Dissertations into practice' feature. AB - The 'Dissertations into practice' feature began life in March 2012 with a dual aim: to encourage students and new professionals to write for publication and to highlight the impact of student research on policy and practice. This article reflects on the initiative and to summarise what has been achieved so far. It highlights the diverse range of contributions to the feature so far and proves that student research can and does influence policy and practice. It also demonstrates that, with a bit of encouragement and support, students are willing and able to write for academic publication. AM. PMID- 26268520 TI - International trends in health science librarianship part 15: West Africa (Ghana, Nigeria, Senegal). AB - This is the 15th in a series of articles exploring international trends in health science librarianship in the 21st century. It is the third of four articles pertaining to different regions in the African continent. The present issue focuses on countries in West Africa (Ghana, Nigeria and Senegal). The next feature column will investigate trends in North Africa. JM. PMID- 26268521 TI - Learning to teach: how a formal teaching qualification improved our practice. AB - In this article, guest writers Sonya Lipczynska and Clare Crowley from King's College London discuss the learning that occurred when they undertook a Postgraduate Certificate in Academic Practice in Higher Education (PGCAPHE). In particular, they identify how their exploration of relevant learning and teaching theory on the course helped them to evaluate their library instruction teaching practice with medical and dental students. They highlight how they made changes and improvements to the delivery of these sessions based on greater consideration of inclusivity and the characteristics of both individuals and broader student groups. They also discuss the successes of new teaching practices that they experimented with, and reflect on how they have developed as educators as a result of this. H.S. PMID- 26268522 TI - IFNgamma+ Treg in-vivo and in-vitro represent both activated nTreg and peripherally induced aTreg and remain phenotypically stable in-vitro after removal of the stimulus. AB - BACKGROUND: IFNgamma-producing CD4+CD25+Foxp3+CD127- Treg represent the first line of Treg during an immune response. In the present study we determined whether IFNgamma+ Treg in-vivo and in-vitro are Helios-positive representing activated natural (nTreg) or Helios-negative representing adaptive Treg (aTreg) and whether they originate from CD4+CD25+ and/or CD4+CD25- PBL. Furtheron, we investigated whether they are inducible by recombinant IFNgamma (rIFNgamma) as a single stimulus, decrease in-vitro after elimination of the stimulus, and have a demethylated Foxp3 Treg-specific demethylated region (TSDR) which is associated with stable Foxp3 expression. METHOD: Subsets of IFNgamma+ Treg were determined in peripheral blood of healthy controls using eight-color flow cytometry and were further investigated in-vitro. Foxp3 TSDR methylation status was determined using bisulphite polymerase chain reaction (PCR) and high resolution melt (HRM) analysis. RESULTS: Nearly all Treg in the peripheral blood were Helios+IFNgamma- (1.9 +/- 1.1/MUl) and only few were Helios+IFNgamma+ or Helios-IFNgamma+ Treg (both 0.1 +/- 0.1/MUl). Enriched IFNgamma+ Treg subsets showed in part strong Foxp3 TSDR demethylation. In-vitro, rIFNgamma was unable to induce Treg. CD4+CD25+ enriched PBL stimulated with PMA/Ionomycin in the presence of rIFNgamma were rather resistant to the effect of rIFNgamma, in contrast to CD4+CD25- enriched PBL which showed increasing total Treg with Helios+ Treg switching from IFNgamma- to IFNgamma+ and increasing Helios-IFNgamma+ Treg. The data indicate that rIFNgamma, in combination with a polyclonal stimulus, activates nTreg and induces aTreg. When phorbol 12-myristate 13-acetate (PMA)/Ionomycin was washed out from the cell culture after 6 h stimulation, Treg induction continued for at least 96 h of cell culture, contradicting the hypothesis that removal of the stimulus results in significant decrease of IFNgamma- and IFNgamma+ CD4+CD25+Foxp3+CD127- Treg due to loss of Foxp3 expression. CONCLUSIONS: IFNgamma+Helios- aTreg as well as IFNgamma+Helios+ nTreg are detectable in the blood of healthy individuals, show in part strong Foxp3 TSDR demethylation and are inducible in-vitro. The present data provide further insight concerning the in-vivo and in-vitro characteristics of IFNgamma+ Treg and help to understand their role in immunoregulation. Alloantigen-specific demethylated IFNgamma+Helios+ nTreg might represent a suitable marker for monitoring graft specific immunosuppression in renal transplant recipients. PMID- 26268523 TI - Three-Dimensional Study of the Terminal Portion in Sprague-Dawley Rat Ejaculatory Ducts. AB - In mammals, a pair of ejaculatory ducts exists in the urethra at the seminal colliculus. The detailed anatomical structures of the distal end of the ejaculatory ducts of Sprague-Dawley rats were investigated by the computer assisted three-dimensional reconstruction analysis using light-microscopic serial sections. A three-dimensional reconstruction revealed that in adult rats, the ejaculatory sinus pair consists of two parts: the cranial section - a compartment region composed of a fusion of the ampullary gland duct and the seminal vesicle duct, and the caudal section - a grooved region composed of a long slitlike ejaculatory ostium that extends into the urethra on both sides of the seminal colliculus. But the sphincter structure was not observed. The long axis of the compartment region was approximately 58 MUm in length, and that of the groove region was approximately 495 MUm. Although many epithelial glands ducts were distributed throughout the ejaculatory sinuses, the prostate and coagulation gland ducts did not open in these sinuses. The urethra was composed of transitional epithelium, while the ejaculatory sinuses were composed of single to stratified cuboidal epithelium. The ejaculatory ducts continued to the ejaculatory ostium in male adult Sprague-Dawley rat were composed of the seminal vesicle ducts received the ampullary gland ducts. PMID- 26268524 TI - Cerebral Lesions at Fetal Magnetic Resonance Imaging and Neurologic Outcome After Single Fetal Death in Monochorionic Twins. AB - BACKGROUND: Single fetal death (sFD) in monochorionic twin pregnancies is associated with substantial morbidity and mortality in the survivor. The aim of our study was to evaluate the rate of cerebral lesions detected at fetal Magnetic Resonance Imaging (MRI) and to correlate the results with the neurologic outcome of the survivors of monochorionic twin pregnancies after sFD. METHODS: Between 2005 and 2012, 11 monochorionic twin pregnancies with sFD and subsequent fetal MRI of the survivor were included. All neonates underwent neurologic assessment after birth and 56% of surviving infants underwent long-term neurologic assessment. MRI findings and neurologic outcome of the survivors were evaluated. RESULTS: Gestational age at sFD was 20.9 (+/-2.9) weeks; 55% (6/11) of survivors of monochorionic twin pregnancies after sFD showed cerebral lesions at fetal MRI; 72% (8/11) of all survivors had normal neonatal neurologic outcome: all survivors with normal fetal MRI and 50% of survivors with cerebral lesions at fetal MRI. Long-term neurologic assessment was normal in all tested patients with normal fetal MRI and in one of three tested patients with cerebral lesions at fetal MRI. CONCLUSION: Survivors of monochorionic twin pregnancies after sFD show a high rate of cerebral lesions at fetal MRI. The importance of cerebral lesions at fetal MRI in survivors after sFD in monochorionic twin pregnancies is uncertain. All tested survivors with normal fetal MRI showed normal neurologic outcome but only one of three survivors with cerebral lesions at fetal MRI showed normal long term neurologic outcome. PMID- 26268525 TI - Responsibility and intellectual property in synthetic biology: A proposal for using Responsible Research and Innovation as a basic framework for intellectual property decisions in synthetic biology. PMID- 26268527 TI - Metadata Correction: A Web-Based Tool for Patient Triage in Emergency Department Settings: Validation Using the Emergency Severity Index. PMID- 26268528 TI - Identification of a Highly Conserved Allosteric Binding Site on Mnk1 and Mnk2. AB - Elevated levels of phosphorylated eukaryotic initiation factor 4E (eIF4E) have been implicated in many tumor types, and mitogen activated protein kinase interacting kinases (Mnks) are the only known kinases that phosphorylate eIF4E at Ser209. The phosphorylation of eIF4E is essential for oncogenic transformation but is of no significance to normal growth and development. Pharmacological inhibition of Mnks therefore provides a nontoxic and effective strategy for cancer therapy. However, a lack of specific Mnk inhibitors has confounded pharmacological target validation and clinical development. Herein, we report the identification of a novel series of Mnk inhibitors and their binding modes. A systematic workflow has been established to distinguish between type III and type I/II inhibitors. A selection of 66 compounds was tested for Mnk1 and Mnk2 inhibition, and 9 out of 20 active compounds showed type III interaction with an allosteric site of the proteins. Most of the type III inhibitors exhibited dual Mnk1 and Mnk2 activities and demonstrated potent antiproliferative properties against the MV4-11 acute myeloid leukemia cell line. Interestingly, ATP /substrate-competitive inhibitors were found to be highly selective for Mnk2, with little or no activity for Mnk1. Our study suggests that Mnk1 and Mnk2 share a common structure of the allosteric inhibitory binding site but possess different structural features of the ATP catalytic domain. The findings will assist in the future design and development of Mnk targeted anticancer therapeutics. PMID- 26268526 TI - Expanding the ubiquitin code through post-translational modification. AB - Ubiquitylation is among the most prevalent post-translational modifications (PTMs) and regulates numerous cellular functions. Interestingly, ubiquitin (Ub) can be itself modified by other PTMs, including acetylation and phosphorylation. Acetylation of Ub on K6 and K48 represses the formation and elongation of Ub chains. Phosphorylation of Ub happens on multiple sites, S57 and S65 being the most frequently modified in yeast and mammalian cells, respectively. In mammals, the PINK1 kinase activates ubiquitin ligase Parkin by phosphorylating S65 of Ub and of the Parkin Ubl domain, which in turn promotes the amplification of autophagy signals necessary for the removal of damaged mitochondria. Similarly, TBK1 phosphorylates the autophagy receptors OPTN and p62 to initiate feedback and feedforward programs for Ub-dependent removal of protein aggregates, mitochondria and pathogens (such as Salmonella and Mycobacterium tuberculosis). The impact of PINK1-mediated phosphorylation of Ub and TBK1-dependent phosphorylation of autophagy receptors (OPTN and p62) has been recently linked to the development of Parkinson's disease and amyotrophic lateral sclerosis, respectively. Hence, the post-translational modification of Ub and its receptors can efficiently expand the Ub code and modulate its functions in health and disease. PMID- 26268529 TI - Breathing Stimulant Compounds Inhibit TASK-3 Potassium Channel Function Likely by Binding at a Common Site in the Channel Pore. AB - Compounds PKTHPP (1-{1-[6-(biphenyl-4-ylcarbonyl)-5,6,7,8-tetrahydropyrido[4,3-d] pyrimidin-4-yl]piperidin-4-yl}propan-1-one), A1899 (2''-[(4 methoxybenzoylamino)methyl]biphenyl-2-carboxylic acid 2,4-difluorobenzylamide), and doxapram inhibit TASK-1 (KCNK3) and TASK-3 (KCNK9) tandem pore (K2P) potassium channel function and stimulate breathing. To better understand the molecular mechanism(s) of action of these drugs, we undertook studies to identify amino acid residues in the TASK-3 protein that mediate this inhibition. Guided by homology modeling and molecular docking, we hypothesized that PKTHPP and A1899 bind in the TASK-3 intracellular pore. To test our hypothesis, we mutated each residue in or near the predicted PKTHPP and A1899 binding site (residues 118-128 and 228-248), individually, to a negatively charged aspartate. We quantified each mutation's effect on TASK-3 potassium channel concentration response to PKTHPP. Studies were conducted on TASK-3 transiently expressed in Fischer rat thyroid epithelial monolayers; channel function was measured in an Ussing chamber. TASK-3 pore mutations at residues 122 (L122D, E, or K) and 236 (G236D) caused the IC50 of PKTHPP to increase more than 1000-fold. TASK-3 mutants L122D, G236D, L239D, and V242D were resistant to block by PKTHPP, A1899, and doxapram. Our data are consistent with a model in which breathing stimulant compounds PKTHPP, A1899, and doxapram inhibit TASK-3 function by binding at a common site within the channel intracellular pore region, although binding outside the channel pore cannot yet be excluded. PMID- 26268531 TI - Iatrogenic CJD due to pituitary-derived growth hormone with genetically determined incubation times of up to 40 years. AB - Patients with iatrogenic Creutzfeldt-Jakob disease due to administration of cadaver-sourced growth hormone during childhood are still being seen in the UK 30 years after cessation of this treatment. Of the 77 patients who have developed iatrogenic Creutzfeldt-Jakob disease, 56 have been genotyped. There has been a marked change in genotype profile at polymorphic codon 129 of the prion protein gene (PRNP) from predominantly valine homozygous to a mixed picture of methionine homozygous and methionine-valine heterozygous over time. The incubation period of iatrogenic Creutzfeldt-Jakob disease is significantly different between all three genotypes. This experience is a striking contrast with that in France and the USA, which may relate to contamination of different growth hormone batches with different strains of human prions. We describe the clinical, imaging, molecular and autopsy features in 22 of 24 patients who have developed iatrogenic Creutzfeldt-Jakob disease in the UK since 2003. Mean age at onset of symptoms was 42.7 years. Gait ataxia and lower limb dysaesthesiae were the most frequent presenting symptoms. All had cerebellar signs, and the majority had myoclonus and lower limb pyramidal signs, with relatively preserved cognitive function, when first seen. There was a progressive decline in neurological and cognitive function leading to death after 5-32 (mean 14) months. Despite incubation periods approaching 40 years, the clinical duration in methionine homozygote patients appeared to be shorter than that seen in heterozygote patients. MRI showed restricted diffusion in the basal ganglia, thalamus, hippocampus, frontal and the paracentral motor cortex and cerebellar vermis. The electroencephalogram was abnormal in 15 patients and cerebrospinal fluid 14-3-3 protein was positive in half the patients. Neuropathological examination was conducted in nine patients. All but one showed synaptic prion deposition with numerous kuru type plaques in the basal ganglia, anterior frontal and parietal cortex, thalamus, basal ganglia and cerebellum. The patient with the shortest clinical duration had an atypical synaptic deposition of abnormal prion protein and no kuru plaques. Taken together, these data provide a remarkable example of the interplay between the strain of the pathogen and host prion protein genotype. Based on extensive modelling of human prion transmission barriers in transgenic mice expressing human prion protein on a mouse prion protein null background, the temporal distribution of codon 129 genotypes within the cohort of patients with iatrogenic Creutzfeldt-Jakob disease in the UK suggests that there was a point source of infecting prion contamination of growth hormone derived from a patient with Creutzfeldt-Jakob disease expressing prion protein valine 129. PMID- 26268532 TI - Restricted sedation and absence of cognitive impairments after administration of intranasal scopolamine. AB - INTRODUCTION: Space motion sickness in astronauts during spaceflight causes significant discomfort, which might impede their functionality. Pharmacological treatment has been mainly restricted to promethazine. Transdermal and oral scopolamine have also been used in space; however, their use was reduced due to unpredictable effectiveness and side effects. Recently, intranasal scopolamine administration has gained much interest, since this route ensures fast and reliable absorption with a decreased incidence of undesirable side effects. The aim of this study was to evaluate the effect of intranasal scopolamine on cognitive performance and to determine its side effects. METHODS: This double blind, placebo controlled, repeated measures study evaluated vigilant attention, short-term memory, implicit memory and working memory. Side effects were reported on a 22-item questionnaire and sleepiness was assessed by the Karolinska, Stanford and Epworth Sleepiness Scales. RESULTS: Scopolamine had no effect on cognitive function. Only the Karolinska score was significantly increased for scopolamine compared to placebo. Participants reported a dry mouth and dizziness after receiving scopolamine. DISCUSSION: Results show that intranasal scopolamine did not impair cognitive performance. Intranasal scopolamine might be a good alternative to promethazine for the alleviation of space motion sickness, since the agent has minimal sedative effects and does not hamper cognitive performance. PMID- 26268534 TI - Limited reproducibility of 24-h ambulatory blood pressure monitoring. AB - Results of 24-h ambulatory blood pressure monitoring (ABPM) including average blood pressure, variability, and nocturnal dipping are considered the gold standard for diagnosis and the best predictor of the future end organ damage in chronic hypertension. Here we report on the reproducibility of ABPM results for these three measures over a period of months. A total of 35 hypertensive patients (43% female, mean age 64 years), underwent two separate ABPM recordings within 14 weeks, with unchanged medical treatment and lifestyle in the interim. The day and night average blood pressure, dipping status of systolic pressure, and the standard deviation of systolic and diastolic blood pressure as a measure of variability were compared between the two recordings. Individual values for average systolic and diastolic pressures showed only a modest correlation between the two measurements (r = 0.56, r = 0.81, p < 0.01). Standard deviations of 24-h pressure were also positively but weakly correlated (r = 0.4, p < 0.001). The occurrence of dipping was reproducible in 71% of the patients. Average blood pressure, pressure variability, and dipping as assessed by ABPM are only moderately reproducible. Clinical decision-making based on single ABPM datasets should be made with caution, and repetition of ABPM seems justified in some cases. PMID- 26268530 TI - GWAS of longitudinal amyloid accumulation on 18F-florbetapir PET in Alzheimer's disease implicates microglial activation gene IL1RAP. AB - Brain amyloid deposition is thought to be a seminal event in Alzheimer's disease. To identify genes influencing Alzheimer's disease pathogenesis, we performed a genome-wide association study of longitudinal change in brain amyloid burden measured by (18)F-florbetapir PET. A novel association with higher rates of amyloid accumulation independent from APOE (apolipoprotein E) epsilon4 status was identified in IL1RAP (interleukin-1 receptor accessory protein; rs12053868-G; P = 1.38 * 10(-9)) and was validated by deep sequencing. IL1RAP rs12053868-G carriers were more likely to progress from mild cognitive impairment to Alzheimer's disease and exhibited greater longitudinal temporal cortex atrophy on MRI. In independent cohorts rs12053868-G was associated with accelerated cognitive decline and lower cortical (11)C-PBR28 PET signal, a marker of microglial activation. These results suggest a crucial role of activated microglia in limiting amyloid accumulation and nominate the IL-1/IL1RAP pathway as a potential target for modulating this process. PMID- 26268533 TI - Better sexual acceptability of agomelatine (25 and 50 mg) compared to escitalopram (20 mg) in healthy volunteers. A 9-week, placebo-controlled study using the PRSexDQ scale. AB - The present double-blind, placebo-controlled study evaluates the effects of agomelatine and the selective serotonin reuptake inhibitor escitalopram on sexual dysfunction in healthy men and women. METHODS: A total of 133 healthy volunteers (67 men, 66 women) were randomly assigned to agomelatine (25 or 50 mg) or escitalopram (20 mg) or placebo for nine weeks. Sexual acceptability was evaluated by using the psychotropic-related sexual dysfunction questionnaire 5 items total score and sexual dysfunction relative to each sub-score (in 110 volunteers with sexual activity). Sexual dysfunction was evaluated at baseline and after two, five and eight weeks of treatment and one week after drug discontinuation. RESULTS: The psychotropic-related sexual dysfunction questionnaire 5-items total score was significantly lower in both agomelatine groups versus escitalopram at all visits (p < 0.01 to p < 0.0001) with no difference between agomelatine and placebo nor between both agomelatine doses. Similar results were observed after drug discontinuation. The total score was significantly higher in the escitalopram group than in the placebo group at each post-baseline visit (p < 0.01 to p < 0.001). Similar results were observed regardless of volunteers' gender. Compared to placebo, only escitalopram significantly impaired dysfunction relative to "delayed orgasm or ejaculation" (p < 0.01) and "absence of orgasm or ejaculation" (p < 0.05 to p < 0.01). The percentage of participants with a sexual dysfunction was higher in the escitalopram group than in agomelatine groups (p < 0.01 to p < 0.05) and placebo (p < 0.01). CONCLUSION: The study confirms the better sexual acceptability profile of agomelatine (25 or 50 mg) in healthy men and women, compared to escitalopram. TRIAL REGISTRATION NAME: Evaluation of the effect of agomelatine and escitalopram on emotions and motivation in healthy male and female volunteers. TRIAL REGISTRATION NUMBER: ISRCTN75872983. PMID- 26268535 TI - Metastatic lymph node status in the central compartment of papillary thyroid carcinoma: A prognostic factor of locoregional recurrence. AB - BACKGROUND: The purpose of this study was to present our focus on the lymph node status in the central compartment and evaluate the relevant factors and disease recurrence. METHODS: Between January 2004 and December 2009, 1040 patients were diagnosed with papillary thyroid carcinoma (PTC) and underwent surgery. RESULTS: The number of metastatic lymph nodes was a significant predictor for recurrence conferring a hazard ratio of 1.36 (confidence interval = 1.103-1.680; p = .004). The receiver operating characteristic (ROC) curve was calculated to determine the cutoff number of lymph nodes that predicted recurrence with the highest sensitivity and specificity (area under the ROC curve, 0.794; SE, 0.077; p = .001). The sensitivity/specificity of >3 metastatic lymph nodes for predicting recurrence was 63.6%/77.0%, respectively. CONCLUSION: The number of metastatic lymph nodes in the central compartment was a statistical significant predictive factor associated with disease recurrence. Further study is required to confirm the relationship between the number of lymph nodes and disease recurrence. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1172-E1176, 2016. PMID- 26268536 TI - Multimorbidity and the inequalities of global ageing: a cross-sectional study of 28 countries using the World Health Surveys. AB - BACKGROUND: Multimorbidity defined as the "the coexistence of two or more chronic diseases" in one individual, is increasing in prevalence globally. The aim of this study is to compare the prevalence of multimorbidity across low and middle income countries (LMICs), and to investigate patterns by age and education, as a proxy for socio-economic status (SES). METHODS: Chronic disease data from 28 countries of the World Health Survey (2003) were extracted and inter-country socio-economic differences were examined by gross domestic product (GDP). Regression analyses were applied to examine associations of education with multimorbidity by region adjusted for age and sex distributions. RESULTS: The mean world standardized multimorbidity prevalence for LMICs was 7.8 % (95 % CI, 7.79 % - 7.83 %). In all countries, multimorbidity increased significantly with age. A positive but non-linear relationship was found between country GDP and multimorbidity prevalence. Trend analyses of multimorbidity by education suggest that there are intergenerational differences, with a more inverse education gradient for younger adults compared to older adults. Higher education was significantly associated with a decreased risk of multimorbidity in the all region analyses. CONCLUSIONS: Multimorbidity is a global phenomenon, not just affecting older adults in HICs. Policy makers worldwide need to address these health inequalities, and support the complex service needs of a growing multimorbid population. PMID- 26268538 TI - A highly stable minimally processed plant-derived recombinant acetylcholinesterase for nerve agent detection in adverse conditions. AB - Although recent innovations in transient plant systems have enabled gram quantities of proteins in 1-2 weeks, very few have been translated into applications due to technical challenges and high downstream processing costs. Here we report high-level production, using a Nicotiana benthamiana/p19 system, of an engineered recombinant human acetylcholinesterase (rAChE) that is highly stable in a minimally processed leaf extract. Lyophylized clarified extracts withstand prolonged storage at 70 degrees C and, upon reconstitution, can be used in several devices to detect organophosphate (OP) nerve agents and pesticides on surfaces ranging from 0 degrees C to 50 degrees C. The recent use of sarin in Syria highlights the urgent need for nerve agent detection and countermeasures necessary for preparedness and emergency responses. Bypassing cumbersome and expensive downstream processes has enabled us to fully exploit the speed, low cost and scalability of transient production systems resulting in the first successful implementation of plant-produced rAChE into a commercial biotechnology product. PMID- 26268537 TI - MinC/MinD copolymers are not required for Min function. AB - In Escherichia coli, precise placement of the cytokinetic Z ring at midcell requires the concerted action of the three Min proteins. MinD activates MinC, an inhibitor of FtsZ, at least in part, by recruiting it to the membrane and targeting it to the Z ring, while MinE stimulates the MinD ATPase inducing an oscillation that directs MinC/MinD activity away from midcell. Recently, MinC and MinD were shown to form copolymers of alternating dimers of MinC and MinD, and it was suggested that these copolymers are the active form of MinC/MinD. Here, we use MinD mutants defective in binding MinC to generate heterodimers with wild type MinD that are unable to form MinC/MinD copolymers. Similarly, MinC mutants defective in binding to MinD were used to generate heterodimers with wild-type MinC that are unable to form copolymers. Such heterodimers are active and in the case of MinC were shown to mediate spatial regulation of the Z ring demonstrating that MinC/MinD copolymer formation is not required. Our results are consistent with a model in which a membrane anchored MinC/MinD complex is targeted to the Z ring through the conserved carboxy tail of FtsZ leading to breakage of FtsZ filaments. PMID- 26268540 TI - Difficidin and bacilysin from Bacillus amyloliquefaciens FZB42 have antibacterial activity against Xanthomonas oryzae rice pathogens. AB - Bacterial blight and bacterial leaf streak are serious, economically damaging, diseases of rice caused by the bacteria Xanthomonas oryzae pv. oryzae and X. oryzae pv. oryzicola. Bacillus amyloliquefaciens FZB42 was shown to possess biocontrol activity against these Xanthomonas strains by producing the antibiotic compounds difficidin and bacilysin. Analyses using fluorescence, scanning electron and transmission electron microscopy revealed difficidin and bacilysin caused changes in the cell wall and structure of Xanthomonas. Biological control experiments on rice plants demonstrated the ability of difficidin and bacilysin to suppress disease. Difficidin and bacilysin caused downregulated expression of genes involved in Xanthomonas virulence, cell division, and protein and cell wall synthesis. Taken together, our results highlight the potential of B. amyloliquefaciens FZB42 as a biocontrol agent against bacterial diseases of rice, and the utility of difficidin and bacilysin as antimicrobial compounds. PMID- 26268541 TI - On the optimization of imaging protocol for the mapping of cerebrovascular reactivity. AB - BACKGROUND: To devise an improved blood-oxygen-level-dependent (BOLD) imaging protocol for cerebrovascular reactivity (CVR) measurement that can remove a known artifact of negative values. METHODS: Theoretical and simulation studies were first performed to understand the biophysical mechanism of the negative CVR signals, through which improved BOLD sequence parameters were proposed. This was achieved by equating signal intensities between cerebrospinal fluid and blood, by means of shortening the echo time (TE) of the BOLD sequence. Then, 10 healthy volunteers were recruited to participate in an experimental study, in which we compared the CVR results of two versions of the optimized ("Opt1" and "Opt2") protocols with that of the standard protocol at 3 Tesla. Two sessions were performed for each subject to test the reproducibility of all three protocols. RESULTS: Experimental results demonstrated that the optimized protocols resulted in elimination of negative-CVR voxels. Quantitative CVR results were compared across protocols, which show that the optimized protocols yielded smaller CVR values (Opt1: 0.16 +/- 0.01 %BOLD/mmHg CO2 ; Opt2: 0.15 +/- 0.01 %BOLD/mmHg CO2 ) than (P < 0.001) the standard protocol (0.21 +/- 0.01 %BOLD/mmHg CO2 ), but the CNR was comparable (P = 0.1) to the standard protocol. The coefficient-of variation between repetitions was found to be 5.6 +/- 1.4%, 6.3 +/- 1.6%, and 6.9 +/- 0.9% for the three protocols, but there were no significant differences (P = 0.65). CONCLUSION: Based on the theoretical and experimental results obtained from this study, we suggest that the use of a TE shorter than those used in fMRI is necessary to minimize negative artifact in CVR results. PMID- 26268544 TI - Transcatheter mitral valve-in-ring implantation in prohibitive surgical risk patients: Single center initial experience in the United States. AB - Surgical mitral annuloplasty ring failure can result in symptomatic mitral stenosis or regurgitation which carries significant morbidity and mortality. Reoperation carries high surgical risks and the feasibility of transcatheter mitral valve-in-ring implantation is suggested by several case reports and series. In this article, we report two MVIR procedures focusing on preprocedural planning issues and intraprocedural tips. (c) 2015 Wiley Periodicals, Inc. PMID- 26268542 TI - Formation of helical membrane tubes around microtubules by single-headed kinesin KIF1A. AB - The kinesin-3 motor KIF1A is in charge of vesicular transport in neuronal axons. Its single-headed form is known to be very inefficient due to the presence of a diffusive state in the mechanochemical cycle. However, recent theoretical studies have suggested that these motors could largely enhance force generation by working in teams. Here we test this prediction by challenging single-headed KIF1A to extract membrane tubes from giant vesicles along microtubule filaments in a minimal in vitro system. Remarkably, not only KIF1A motors are able to extract tubes but they feature a novel phenomenon: tubes are wound around microtubules forming tubular helices. This finding reveals an unforeseen combination of cooperative force generation and self-organized manoeuvreing capability, suggesting that the diffusive state may be a key ingredient for collective motor performance under demanding traffic conditions. Hence, we conclude that KIF1A is a genuinely cooperative motor, possibly explaining its specificity to axonal trafficking. PMID- 26268545 TI - Perfusion vector-a new method to quantify myocardial perfusion scintigraphy images: a simulation study with validation in patients. AB - BACKGROUND: The interpretation of myocardial perfusion scintigraphy (MPS) largely relies on visual assessment by the physician of the localization and extent of a perfusion defect. The aim of this study was to introduce the concept of the perfusion vector as a new objective quantitative method for further assisting the visual interpretation and to test the concept using simulated MPS images as well as patients. METHODS: The perfusion vector is based on calculating the difference between the anatomical centroid and the perfusion center of gravity of the left ventricle. Simulated MPS images were obtained using the SIMIND Monte Carlo program together with XCAT phantom. Four different-sized anterior and four lateral defects were simulated, and perfusion vector components x-, y-, and z axes were calculated. For the patient study, 40 normal and 80 abnormal studies were included. Perfusion vectors were compared between normal and abnormal (apical, inferior, anterior, and lateral ischemia or infarction) studies and also correlated to the defect size. RESULTS: For simulated anterior defects, the stress perfusion vector component on the y-axis (anterior-inferior direction) increased in proportion to the defect size. For the simulated lateral defects, the stress perfusion vector component on the x-axis (septal-lateral direction) decreased in proportion to the defect size. When comparing normal and abnormal patients, there was a statistically significant difference for the stress perfusion vector on the x-axis for apical and lateral defects; on the y-axis for apical, inferior, and lateral defects; and on the z-axis (basal-apical direction) for apical, anterior, and lateral defects. A significant difference was shown for the difference vector magnitude (stress/rest) between normal and ischemic patients (p = 0.001) but not for patients with infarction. The correlation between the defect size and stress vector magnitude was also found to be significant (p < 0.001). CONCLUSIONS: The concept of the perfusion vector introduced in this study is shown to have potential in assisting the visual interpretation in MPS studies. Further studies are needed to validate the concept in patients. PMID- 26268546 TI - Self-Interaction Chromatography of mAbs: Accurate Measurement of Dead Volumes. AB - PURPOSE: Measurement of the second virial coefficient B22 for proteins using self interaction chromatography (SIC) is becoming an increasingly important technique for studying their solution behaviour. In common with all physicochemical chromatographic methods, measuring the dead volume of the SIC packed column is crucial for accurate retention data; this paper examines best practise for dead volume determination. METHOD: SIC type experiments using catalase, BSA, lysozyme and a mAb as model systems are reported, as well as a number of dead column measurements. RESULTS: It was observed that lysozyme and mAb interacted specifically with Toyopearl AF-Formyl dead columns depending upon pH and [NaCl], invalidating their dead volume usage. Toyopearl AF-Amino packed dead columns showed no such problems and acted as suitable dead columns without any solution condition dependency. Dead volume determinations using dextran MW standards with protein immobilised SIC columns provided dead volume estimates close to those obtained using Toyopearl AF-Amino dead columns. CONCLUSION: It is concluded that specific interactions between proteins, including mAbs, and select SIC support phases can compromise the use of some standard approaches for estimating the dead volume of SIC columns. Two other methods were shown to provide good estimates for the dead volume. PMID- 26268548 TI - Synergistic Photobactericidal Activity Based on Ultraviolet-A Irradiation and Ferulic Acid Derivatives. AB - Ultraviolet-A (UV-A)-mediated bactericidal activity was enhanced by combined treatment with trans-ferulic acid (trans-FA, compound 1) or its derivatives. Derivative compounds 4 and 10 contain a phenyl group or an l-tyrosine HCl tert butyl ester, respectively, linked to the carboxyl group of trans-FA. Of the three compounds, 10 exhibited the highest synergistic activity in a photobactericidal assay based on treating Escherichia coli with a derivative compound and UV-A irradiation (wavelength 350-385 nm). Inactivation of viable cells at a 4.9 J cm( 2) UV-A fluence increased from 1.90 to 5.19 logs in the presence of 10 (100 MUm); a 4.95-log inactivation was achieved with 10 (5 MUm) and a 7.4 J cm(-2) UV-A fluence. Addition of antioxidants significantly suppressed photosynergistic bactericidal activity, suggesting that reactive oxygen species (ROS) are involved in the combined bactericidal mechanism. Flow cytometry revealed that combined treatment with UV-A and compound 10, which showed the highest photobactericidal activity, generates an excess of oxidative radicals in bacterial cells. The bactericidal activity of compound 10 may be due to electrostatic interaction between the molecule's cationic moiety and the cell surface, followed by amplification of ROS generation in the cells. PMID- 26268549 TI - [A smear method for measuring anti-cancer drugs residues in hospitals]. AB - OBJECTIVES: Anti-cancer drugs are harmful to healthy persons. In recent years, occupational exposure to anti-cancer drugs has become a major concern to health care workers. To address this issue, a smear method was developed to measure widely using anti-cancer drugs depositing on the floors, safety cabinet surfaces, and tables in hospital. METHODS: Ten kinds of widely used anti-cancer drugs, paclitaxel, vincristine, docetaxel, vinorelbine, irinotecan, methotrexate, oxaliplatin, cyclophosphamide, gemcitabine and fluorouracil were collected by smearing material surfaces with methanol impregnated cellulose filter paper and/or polypropylene nonwoven. The collected anti-cancer drugs are extracted in 5 ml of 0.01% (v/v) hydrazine/methanol solution by sonication. The extracted solution was filtered and concentrated to prepare 1ml of sample solution. Then, the anti-cancer drugs in the sample solution were simultaneously measured by LC/MS. RESULTS: The anti-cancer drugs excepting fluorouracil spread on P-tile surface were measured with recoveries of 37-101% and standard deviations (SD) of 1.8-19%. All 10 of the anti-cancer drugs on a stainless steel plate surface were measured with the recoveries of 35-111% and SD of 1.3-11%. CONCLUSIONS: Using this smear method, 9 or 10 kinds of widely used anti-cancer drug residues in hospital, possibly exposed to health care workers, were grasped. PMID- 26268547 TI - Soybean transcription factor ORFeome associated with drought resistance: a valuable resource to accelerate research on abiotic stress resistance. AB - BACKGROUND: Whole genome sequencing provides the most comprehensive collection of an organism's genetic information. The availability of complete genome sequences is expected to dramatically deliver a high impact on biology. However, to achieve this impact in the area of crop improvement, significant efforts are still required on functional genomics, including the areas of gene annotation, cloning, expression profiling, and functional validation. RESULTS: Here we report our efforts in generating the first transcription factor (TF) open reading frame (ORF)eome resource associated with drought resistance in soybean (Glycine max), a major oil/protein crop grown worldwide. This study provides a highly annotated soybean TF-ORFeome associated with drought resistance. It contains information from experimentally verified protein-coding sequences (CDS), expression profiling under several abiotic stresses (drought, salinity, dehydration and ABA), and computationally predicted protein subcellular localization and cis-regulatory elements (CREs) analysis. All the information is available to plant researchers through a freely accessible and user-friendly database, Soybean Knowledge Base (SoyKB). CONCLUSIONS: The soybean TF-ORFeome provides a valuable public resource for functional genomics studies, especially in the area of plant abiotic stresses. It will accelerate findings in the areas of abiotic stresses and lead to the generation of crops with enhanced resistance to multiple stresses. PMID- 26268550 TI - [The association between the presence of occupational health nurses at Japanese worksites and health promotion activities]. AB - OBJECTIVES: The purpose of this study was to determine the association between the presence of occupational health nurses and health promotion activities, relative to the number of employees, and the health promotion policies of the companies. METHODS: We investigated 3,266 companies with at least 50 employees listed on the Tokyo Stock Exchange. Questionnaires were sent by mail, and employees in charge of health management or promotion were asked about health promotion activities at their own worksites. Logistic regression analysis was performed with each type of health promotion activity (nutrition, exercise, sleep, mental health, smoking cessation, alcohol consumption reduction, and oral health) as dependent variables, and the presence of an occupational health nurse as the independent variable. The results were adjusted for the type of industry, total number of company employees, presence of company health promotion policies, and the presence of an occupational health physician. RESULTS: Responses were received from 415 companies (response rate: 12.7%). Occupational health nurses were present at 172 companies (41.4%). Health promotion activities such as (in order of frequency) mental health (295 companies, 71.1%), smoking cessation (133, 32.0%), exercise (99, 23.9%), nutrition (75, 18.1%), oral health (49, 11.8%), sleep (39, 9.4%), and alcohol consumption reduction (26, 6.3%) were being conducted. Setting worksites with no occupational health nurse as a reference, the odds ratios of each health promotion activity of a worksite with one or more occupational health nurses were calculated. The odds ratios of mental health (2.43, 95% confidence interval: 1.32-4.48), smoking cessation (3.70, 2.14-6.38), exercise (4.98, 2.65-9.35), nutrition (8.34, 3.86-18.03), oral health (4.25, 1.87 9.62), and alcohol consumption reduction (8.96, 2.24-35.92) were significant. Stratified analysis using the number of worksite employees, 499 or fewer and 500 or more, also showed significantly higher odds ratios of smoking cessation, exercise, and nutrition activities at worksites of both groups. However, the odds ratios were significant for mental health and oral health activities only at worksites with 499 or fewer employees. CONCLUSIONS: At worksites of listed companies around Japan, those with an occupational health nurse carried out more health promotion activities such as nutrition, exercise, mental health, smoking cessation, alcohol consumption reduction, and oral health than those without, even after adjusting for scale of the company and presence of health promotion policies. This result suggests that the posting of an occupational health nurse to a worksite is associated with the conduct of health promotion activities. PMID- 26268551 TI - Single-Atom Pd1/Graphene Catalyst Achieved by Atomic Layer Deposition: Remarkable Performance in Selective Hydrogenation of 1,3-Butadiene. AB - We reported that atomically dispersed Pd on graphene can be fabricated using the atomic layer deposition technique. Aberration-corrected high-angle annular dark field scanning transmission electron microscopy and X-ray absorption fine structure spectroscopy both confirmed that isolated Pd single atoms dominantly existed on the graphene support. In selective hydrogenation of 1,3-butadiene, the single-atom Pd1/graphene catalyst showed about 100% butenes selectivity at 95% conversion at a mild reaction condition of about 50 degrees C, which is likely due to the changes of 1,3-butadiene adsorption mode and enhanced steric effect on the isolated Pd atoms. More importantly, excellent durability against deactivation via either aggregation of metal atoms or carbonaceous deposits during a total 100 h of reaction time on stream was achieved. Therefore, the single-atom catalysts may open up more opportunities to optimize the activity, selectivity, and durability in selective hydrogenation reactions. PMID- 26268553 TI - Nanoscale resolution in infrared imaging of protein-containing lipid membranes. AB - The precise imaging of biomolecular entities contributes to an understanding of the relationship between their structure and function. However, the resolution of conventional infrared microscopic imaging is diffraction limited and does not exceed a few micrometres. Atomic force microscopy, on the other hand, can detect infrared absorption down to the sub-micrometer level. In the present report, we demonstrate that for multi-bilayer lipid samples containing the plant photosynthetic pigment-protein complex LHCII, the resolution of this latter technique can be better than 20 nm. Such a high resolution is attributable to two factors: (i) the relatively high infrared absorption by the complex that is integrated perpendicular to the plane of the multilayer film, and (ii) the distinctly different mechanical properties and thermal conductivity of the lipid and protein components of the sample. PMID- 26268555 TI - Erratum to: A cluster randomized trial of a multifaceted quality improvement intervention in Brazilian intensive care units: study protocol. PMID- 26268556 TI - The N-terminal ubiquitin-binding region of ubiquitin-specific protease 28 modulates its deubiquitination function: NMR structural and mechanistic insights. AB - The deubiquitinase ubiquitin-specific protease 28 (Usp28) contains a ubiquitin binding region (UBR) composed of one ubiquitin-associated domain (UBA) and one ubiquitin-interacting motif (UIM) at its N-terminus. It is of interest that an additional small ubiquitin-like modifier (SUMO)-interacting motif (SIM) is located next to its UIM. To date, the functional role of the Usp28 UBR is still not understood. To elucidate the regulatory mechanism of the UBR on the full functional display of Usp28, in the present study, NMR and biochemical approaches were applied. The solution structure of Usp28 UBR was obtained, and the key residues responsible for ubiquitin and SUMO1/2 recognition were identified. In addition, we find that the ubiquitin-binding ability of Usp28 UBR was required for full enzymatic activity of Usp28, whereas binding of SUMO1/2 impaired the catalytic activity of the enzyme by competitively blocking its interactions with ubiquitin substrates. Our findings provide a first insight into understanding how the enzymatic activity of Usp28 is regulated by its non-catalytic UBR and endogenous ligands. PMID- 26268557 TI - A paralogue of the phosphomutase-like gene family in Candida glabrata, CgPmu2, gained broad-range phosphatase activity due to a small number of clustered substitutions. AB - Inorganic phosphate is required for a range of cellular processes, such as DNA/RNA synthesis and intracellular signalling. The phosphate starvation inducible phosphatase activity of Candida glabrata is encoded by the gene CgPMU2 (C. glabrata phosphomutase-like protein). CgPMU2 is part of a three-gene family (~75% identical) created through gene duplication in the C. glabrata clade; only CgPmu2 is a PHO-regulated broad range acid phosphatase. We identified amino acids that confer broad range phosphatase activity on CgPmu2 by creating fusions of sections of CgPMU2 with CgPMU1, a paralogue with little broad range phosphatase activity. We used site-directed mutagenesis on various fusions to sequentially convert CgPmu1 to CgPmu2. Based on molecular modelling of the Pmu proteins on to a histidine phosphatase crystal structure, clusters of amino acids were found in two distinct regions that were able to confer phosphatase activity. Substitutions in these two regions together conferred broad phosphatase activity on CgPmu1. Interestingly, one change is a histidine adjacent to the active site histidine of CgPmu2 and it exhibits a novel ability to partially replace the conserved active site histidine in CgPmu2. Additionally, a second amino acid change was able to confer nt phosphatase activity to CgPmu1, suggesting single amino acid changes neofunctionalize CgPmu2. PMID- 26268554 TI - Exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem cells attenuate limb ischemia by promoting angiogenesis in mice. AB - INTRODUCTION: 'Patient-specific' induced pluripotent stem cells (iPSCs) are attractive because they can generate abundant cells without the risk of immune rejection for cell therapy. Studies have shown that iPSC-derived mesenchymal stem cells (iMSCs) possess powerful proliferation, differentiation, and therapeutic effects. Recently, most studies indicate that stem cells exert their therapeutic effect mainly through a paracrine mechanism other than transdifferentiation, and exosomes have emerged as an important paracrine factor for stem cells to reprogram injured cells. The objective of this study was to evaluate whether exosomes derived from iMSCs (iMSCs-Exo) possess the ability to attenuate limb ischemia and promote angiogenesis after transplantation into limbs of mice with femoral artery excision. METHODS: Human iPSCs (iPS-S-01, C1P33, and PCKDSF001C1) were used to differentiate into iMSCs in a modified one-step method. iMSCs were characterized by flow cytometry and multipotent differentiation potential analysis. Ultrafiltration combined with a purification method was used to isolate iMSCs-Exo, and transmission electron microscopy and Western blotting were used to identify iMSCs-Exo. After establishment of mouse hind-limb ischemia with excision of femoral artery and iMSCs-Exo injection, blood perfusion was monitored at days 0, 7, 14, and 21; microvessel density in ischemic muscle was also analyzed. In vitro migration, proliferation, and tube formation experiments were used to analyze the ability of pro-angiogenesis in iMSCs-Exo, and quantitative reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay were used to identify expression levels of angiogenesis-related molecules in human umbilical vein endothelial cells (HUVECs) after being cultured with iMSCs Exo. RESULTS: iPSCs were efficiently induced into iMSC- with MSC-positive and negative surface antigens and osteogenesis, adipogenesis, and chondrogenesis differentiation potential. iMSCs-Exo with a diameter of 57 +/- 11 nm and expressed CD63, CD81, and CD9. Intramuscular injection of iMSCs-Exo markedly enhanced microvessel density and blood perfusion in mouse ischemic limbs, consistent with an attenuation of ischemic injury. In addition, iMSCs-Exo could activate angiogenesis-related molecule expression and promote HUVEC migration, proliferation, and tube formation. CONCLUSION: Implanted iMSCs-Exo was able to protect limbs from ischemic injury via the promotion of angiogenesis, which indicated that iMSCs-Exo may be a novel therapeutic approach in the treatment of ischemic diseases. PMID- 26268558 TI - The solution structures of native and patient monomeric human IgA1 reveal asymmetric extended structures: implications for function and IgAN disease. AB - Native IgA1, for which no crystal structure is known, contains an O galactosylated 23-residue hinge region that joins its Fab and Fc regions. IgA nephropathy (IgAN) is a leading cause of chronic kidney disease in developed countries. Because IgA1 in IgAN often has a poorly O-galactosylated hinge region, the solution structures of monomeric IgA1 from a healthy subject and three IgAN patients with four different O-galactosylation levels were studied. Analytical ultracentrifugation showed that all four IgA1 samples were monomeric with similar sedimentation coefficients, s(0)20,w. X-ray scattering showed that the radius of gyration (Rg) slightly increased with IgA1 concentration, indicating self association, although their distance distribution curves, P(r), were unchanged with concentration. Neutron scattering indicated similar Rg values and P(r) curves, although IgA1 showed a propensity to aggregate in heavy water buffer. A new atomistic modelling procedure based on comparisons with 177000 conformationally-randomized IgA1 structures with the individual experimental scattering curves revealed similar extended Y-shaped solution structures for all four differentially-glycosylated IgA1 molecules. The final models indicated that the N-glycans at Asn(263) were folded back against the Fc surface, the C-terminal tailpiece conformations were undefined and hinge O-galactosylation had little effect on the solution structure. The solution structures for full-length IgA1 showed extended hinges and the Fab and Fc regions were positioned asymmetrically to provide ample space for the functionally-important binding of two FcalphaR receptors to its Fc region. Whereas no link between O-galactosylation and the IgA1 solution structure was detected, an increase in IgA1 aggregation with reduced O-galactosylation may relate to IgAN. PMID- 26268559 TI - A calreticulin-dependent nuclear export signal is involved in the regulation of liver receptor homologue-1 protein folding. AB - As an orphan member of the nuclear receptor family, liver receptor homologue-1 (LRH-1) controls a tremendous range of transcriptional programmes that are essential for metabolism and hormone synthesis. Our previous studies have shown that nuclear localization of the LRH-1 protein is mediated by two nuclear localization signals (NLSs) that are karyopherin/importin-dependent. It is unclear whether LRH-1 can be actively exported from the nucleus to the cytoplasm. In the present study, we describe a nuclear export domain containing two leucine rich motifs [named nuclear export signal (NES)1 and NES2] within the ligand binding domain (LBD). Mutation of leucine residues in NES1 or NES2 abolished nuclear export, indicating that both NES1 and NES2 motifs are essential for full nuclear export activity. This NES-mediated nuclear export was insensitive to the chromosomal region maintenance 1 (CRM1) inhibitor leptomycin B (LMB) or to CRM1 knockdown. However, knockdown of calreticulin (CRT) prevented NES-mediated nuclear export. Furthermore, our data show that CRT interacts with LRH-1 and is involved in the nuclear export of LRH-1. With full-length LRH-1, mutation of NES1 led to perinuclear accumulation of the mutant protein. Immunofluorescence analysis showed that these perinuclear aggregates were co-localized with the centrosome marker, microtubule-associated protein 1 light chain 3 (LC3), ubiquitin and heat shock protein 70 (Hsp70), indicating that the mutant was misfolded and sequestered into aggresome-like structures via the autophagic clearance pathway. Our study demonstrates for the first time that LRH-1 has a CRT dependent NES which is not only required for cytoplasmic trafficking, but also essential for correct protein folding to avoid misfolding-induced aggregation. PMID- 26268560 TI - Methylation of the Gpat2 promoter regulates transient expression during mouse spermatogenesis. AB - Spermatogenesis is a highly regulated process that involves both mitotic and meiotic divisions, as well as cellular differentiation to yield mature spermatozoa from undifferentiated germinal stem cells. Although Gpat2 was originally annotated as encoding a glycerol-3-phosphate acyltransferase by sequence homology to Gpat1, GPAT2 is highly expressed in testis but not in lipogenic tissues and is not up-regulated during adipocyte differentiation. New data show that GPAT2 is required for the synthesis of piRNAs (piwi-interacting RNAs), a group of small RNAs that protect the germ cell genome from retrotransposable elements. In order to understand the relationship between GPAT2 and its role in the testis, we focused on Gpat2 expression during the first wave of mouse spermatogenesis. Gpat2 expression was analysed by qPCR (quantitative real-time PCR), in situ hybridization, immunohistochemistry and Western blotting. Gpat2 mRNA content and protein expression were maximal at 15 dpp (days post partum) and were restricted to pachytene spermatocytes. To achieve this transient expression, both epigenetic mechanisms and trans-acting factors are involved. In vitro assays showed that Gpat2 expression correlates with DNA demethylation and histone acetylation and that it is up-regulated by retinoic acid. Epigenetic regulation by DNA methylation was confirmed in vivo in germ cells by bisulfite sequencing of the Gpat2 promoter. Consistent with the initiation of meiosis at 11 dpp, methylation decreased dramatically. Thus, Gpat2 is expressed at a specific stage of spermatogenesis, consistent with piRNA synthesis and meiosis I prophase, and its on-off expression pattern responds predominantly to epigenetic modifications. PMID- 26268562 TI - Phytate effects on biological hydroxyapatite development. PMID- 26268561 TI - An immunohistochemical study on the expression of sex steroid receptors, Ki-67 and cytokeratins 7 and 20 in feline endometrial adenocarcinomas. AB - BACKGROUND: Endometrial adenocarcinomas are a rare type of tumour in cats. Though different morphologies have been reported, the most frequent histological type of feline endometrial adenocarcinoma (FEA) is the papillary serous. Characterization of molecular markers expression in FEA may contribute to clarify the pathogenesis of these tumours and to assess the differences between normal endometrium and FEA regarding the expression pattern of several proteins. Therefore, this study aimed to evaluate the immunohistochemical profile of a wide panel of antibodies (specific for ER-alpha, PR, Ki-67, CK7 and CK20) in twenty-four cases of FEA. Comparisons were made between FEA and feline normal cyclic endometrium in follicular (n = 13) and luteal (n = 10) stages. Except for Ki-67, all other molecular markers were assessed independently for the intensity of immunolabeling and for the percentage of cells expressing the protein. RESULTS: This study showed that in FEA a loss of expression occurs for ER-alpha (P <= 0.0001) and less markedly also for PR. The lost in sex steroid receptors concerns a decrease in both the proportion of labelled cells and the intensity of immunolabelling (P = 0.002 and P = 0.024, respectively). Proliferative activity, estimated via Ki-67 immunoreaction, significantly increased in FEA as compared to normal endometrium (P <= 0.0001). Feline endometrial adenocarcinomas maintained the CK7+/CK20+ status of normal endometrium. However, FEA showed decreased CK7 intensity of labelling compared to normal endometria (P <= 0.0001) and loss of CK20 expression, both in intensity (P <= 0.0001) and in percentage of positive cells (P = 0.01), compared to normal tissues. CONCLUSIONS: Data gathered in this study suggest that proliferation in FEA accompanies ER-alpha down-regulation, possibly following activation of pathways mediated by local growth factors. Moreover, FEA retains combined expression of CK7 and CK20, as evidenced in normal endometrial epithelia, although a decrease in CK7 expression was observed. PMID- 26268563 TI - Stabilization of Human Immunoglobulin G Encapsulated within Biodegradable Poly (Cyclohexane-1, 4-diyl Acetone Dimethylene Ketal) (PCADK)/ Poly (Lactic-co Glycolic Acid) (PLGA) Blend Microspheres. AB - The aim of this study was to prepare PCADK/PLGA-blend microspheres for improving the stability of human immunoglobulin G (IgG). The short half-life of antibodies limit their development as therapeutic agents, thus PLGA microspheres were prepared to sustained release antibodies and prolong their half-life. However, the acidic intra-microsphere environment causes the loss of antibody stability and activity. In this study, the effect of PCADK or PLGA degradation products on IgG was investigated by size exclusion chromatography (SEC-HPLC), circular dichroism (CD), fluorescence spectroscopy and antigenicity detection. The degradation products of PCADK exerted a larger influence on IgG than that of PLGA. Then PCADK/PLGA microspheres were prepared by the emulsionsolvent evaporation method and systematically characterized and 20% PCADK were selected as the optimal proportion. In addition, the release profile of microspheres and the stability of the released IgG were investigated. The stability of the IgG released from the PCADK/PLGA microspheres was better than that of IgG released from the PLGA microspheres. Confocal laser scanning microscopy (CLSM) was used to determine the pH inside the microspheres. The IgG-loaded PCADK/PLGA microspheres have important advantages over the PLGA microspheres in terms of IgG stability and could be a good carrier to deliver antibodies for the treatment of disease. PMID- 26268564 TI - Non-dipping blood pressure patterns and arterial stiffness parameters in patients with Behcet's disease. AB - Behcet's disease is a multisystemic vasculitis involving veins and arteries of various sizes. Non-dipping status, augmentation index and pulse wave velocity are important determinants of cardiovascular mortality and morbidity. We investigated the non-dipping status and arterial stiffness in patients with Behcet's disease. In this cross-sectional study, we examined the vascular parameters of 96 patients with Behcet's disease (53% female) and 60 age- and sex-matched control subjects. The non-dipping status and arterial distensibility were assessed using a Mobil-O Graph Arteriograph, an automatic oscillometric device. In total, 65.6% of 96 patients were systolic non-dippers, and 34.4% exhibited high augmentation indices. Ten percent of the control subjects were systolic non-dippers, and 11.7% exhibited high augmentation indices. Nocturnal decreases in systolic blood pressure correlated with central systolic blood pressure and diastolic blood pressure, as well as nocturnal decreases in diastolic blood pressure. Furthermore, non-dipper patients with Behcet's disease exhibited higher nocturnal cardiac outputs than did dipper patients with Behcet's disease. Augmentation index correlated negatively with C-reactive protein and correlated positively with both 24 h and nocturnal peripheral resistance, as well as 24 h pulse wave velocity. The patients with high augmentation indices exhibited lower creatinine clearance, as well as lower nocturnal cardiac outputs, higher 24 h peripheral resistance and higher 24 h pulse wave velocities. Non-dipping status and arterial stiffness may exacerbate the harmful cardiovascular effects of the other. In addition to conventional risk factors, non-dipping status and arterial stiffness should be examined during the follow-up evaluations of patients with Behcet's disease. PMID- 26268565 TI - "A randomized, double-blind study of the effects of omega-3 fatty acids (Omegaven) on outcome after major liver resection". AB - BACKGROUND: The body is dependent on the exogenous supply of omega-3 polyunsaturated fatty acids (n3-PUFA). These essential fatty acids are key players in regulating metabolic signaling but also exert anti-inflammatory and anti-carcinogenic properties. The liver is a major metabolic organ involved in fatty acid metabolism. Under experimental conditions, n3-PUFA exert beneficial effect on hepatic steatosis, regeneration and inflammatory insults such as ischemic injury after surgery. Some of these effects have also been observed in human subjects. However, it is unclear whether perioperative administration of n3 PUFA is sufficient to protect the liver from ischemic injury. Therefore, we designed a randomized controlled trial (RCT) assessing n3-PUFA (pre-) conditioning strategies in patients scheduled for liver surgery. METHODS/DESIGN: The Omegaven trial is a multi-centric, double-blind, randomized, placebo- controlled trial applying two single doses of Omegaven or placebo on 258 patients undergoing major liver resection. Primary endpoints are morbidity and mortality one month after hospital discharge, defined by the Clavien- Dindo classification of surgical complications (Ann Surg 240(2):205-13, 2004) as well as the Comprehensive Complication Index (CCI) (Ann Surg 258(1):1-7, 2013). Secondary outcome variables include length of Intensive Care Unit (ICU) and hospital stay, postoperative liver function tests, fatty acid and eicosanoid concentration, inflammatory markers in serum and in liver tissue. An interim analysis is scheduled after the first 30 patients per randomization group. DISCUSSION: Long term administration of n3-PUFA have a beneficial effect on metabolism and hepatic injury. Patients often require surgery without much delay, thus long-term n3-PUFA uptake is not possible. Also, lack of compliance may lead to incomplete n3-PUFA substitution. Hence, perioperative OmegavenTM may provide an easy and controllable way to ensure hepaative application of tic protection. TRIAL REGISTRATION: ClinicalTrial.gov: ID: NCT01884948 , registered June 14, 2013; Institution Ethical Board Approval: KEK-ZH-Nr. 2010-0038; Swissmedic Notification: 2012DR3215. PMID- 26268566 TI - Introgressive hybridizations of Schistosoma haematobium by Schistosoma bovis at the origin of the first case report of schistosomiasis in Corsica (France, Europe). AB - This study concerns the first urinary schistosomiasis case observed in Corsica (France, Europe) occurring in a 12-year-old German boy. The aim was to identify the relationship between this Schistosoma haematobium infection and other schistosomes of the Schistosoma group with terminal-spined ova. Morphological and molecular analyses were conducted on the ova. The results showed that the schistosome responsible for the emergence of schistosomiasis in Corsica was due to S. haematobium introgressed by genes from S. bovis. PMID- 26268567 TI - Schistosoma japonicum protein SjP40 inhibits TGF-beta1-induced activation of hepatic stellate cells. AB - SjP40 is a major egg antigen of Schistosoma japonicum. In the present study, the authors investigated the effect of SjP40 in vitro on transforming growth factor beta1 (TGF-beta1)- stimulated hepatic stellate cells (HSCs). LX-2, an immortalized human HSC line, was treated with purified recombinant SjP40 (rSjP40) in the presence or absence of TGF-beta1. Quantitative real-time polymerase chain reaction and western blot analysis were performed to determine messenger ribonucleic acid and protein of fibrogenic genes and TGF-beta signaling pathway. The results showed that expression of fibrogenic genes was significantly reduced by rSjP40. Furthermore, rSjP40 also suppressed the TGF-beta1-induced upregulation of Smads and ERK proteins. We also found that the effect of rSjP40 on HSCs was similar to SB431542, an inhibitor of type I TGF-beta receptor. In conclusion, the data suggest that SjP40 attenuates HSC activation, which might be, at least in part, mediated by inhibiting the TGF-beta and ERK signaling pathways. PMID- 26268568 TI - First report of genotype #65 of Toxoplasma gondii in pigs. AB - The aim of the present study was to isolate and genotype Toxoplasma gondii from pigs slaughtered for human consumption in northeastern Brazil. Indirect immunofluorescence antibody test (IFAT) was used to screen positive pigs. Tissues samples of animals with antibody titers >=64 were submitted to bioassay in mice. One isolate of T. gondii was obtained, and the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique, using 11 markers (SAG1, SAG2, altSAG2, SAG3, BTUB, GRA6, c228, c292, L358, PK1, and APICO), was applied to evaluate the genetic variability. DNA from reference strains was used as a positive control. By means of genetic analysis, genotype ToxoDB #65 was identified, which is considered an atypical strain. This is the first record of genotype #65 in pigs. Thus, further studies in this region are necessary to determine the genetic variability of T. gondii in pigs and possible impact on public health. PMID- 26268570 TI - Why the C-statistic is not informative to evaluate early warning scores and what metrics to use. AB - Metrics typically used to report the performance of an early warning score (EWS), such as the area under the receiver operator characteristic curve or C-statistic, are not useful for pre-implementation analyses. Because physiological deterioration has an extremely low prevalence of 0.02 per patient-day, these metrics can be misleading. We discuss the statistical reasoning behind this statement and present a novel alternative metric more adequate to operationalize an EWS. We suggest that pre-implementation evaluation of EWSs should include at least two metrics: sensitivity; and either the positive predictive value, number needed to evaluate, or estimated rate of alerts. We also argue the importance of reporting each individual cutoff value. PMID- 26268569 TI - Molecular characterization of Stictodora tridactyla (Trematoda: Heterophyidae) from Kuwait Bay using rDNA ITS and mtCO1. AB - Stictodora tridactyla is an intestinal fluke in the family Heterophyidae that parasitizes shorebirds and mammals, including humans. Its metacercarial cyst stage was reported in the Arabian killifish, Aphanius dispar, at Kuwait Bay. In the present study, Cerithidea cingulata was found to serve as the first intermediate host of S. tridactyla. In order to establish the snail-fish link in the life cycle of S. tridactyla, complete sequences of ribosomal DNA internal transcribed spacer region 1 and 2 (rDNA ITS1 and ITS2) and partial sequence of cytochrome oxidase subunit 1 were obtained for metacercarial cysts isolated from the fish A. dispar and rediae isolated from the snail C. cingulata. Sequence alignment demonstrated that these larval stages belong to the same heterophyid species, S. tridactyla. Phylogenetic analysis based on rDNA ITS1, ITS2, and mtCO1 confirmed the position of S. tridactyla within the Heterophyidae and found it to cluster with Haplorchis spp. The present study represents the first molecular study correlating the larval stages of S. tridactyla using rDNA ITS1, ITS2, and mtCO1 and examining the phylogenetic relationships of S. tridactyla with different heterophyid species. PMID- 26268571 TI - Relationships between structure, ionization profile and sensitivity of exogenous anabolic steroids under electrospray ionization and analysis in human urine using liquid chromatography-tandem mass spectrometry. AB - The relationships between the ionization profile, sensitivity, and structures of 64 exogenous anabolic steroids (groups I-IV) was investigated under electrospray ionization (ESI) conditions. The target analytes were ionized as [M + H](+) or [M + H-nH2 O](+) in the positive mode, and these ions were used as precursor ions for selected reaction monitoring analysis. The collision energy and Q3 ions were optimized based on the sensitivity and selectivity. The limits of detection (LODs) were 0.05-20 ng/mL for the 64 steroids. The LODs for 38 compounds, 14 compounds and 12 compounds were in the range of 0.05-1, 2-5 and 10-20 ng/mL, respectively. Steroids including the conjugated keto-functional group at C3 showed good proton affinity and stability, and generated the [M + H](+) ion as the most abundant precursor ion. In addition, the LODs of steroids using the [M + H](+) ion as the precursor ion were mostly distributed at low concentrations. In contrast, steroids containing conjugated/unconjugated hydroxyl functional groups at C3 generated [M + H - H2 O](+) or [M + H - 2H2 O](+) ions, and these steroids showed relatively high LODs owing to poor stability and multiple ion formation. An LC-MS/MS method based on the present ionization profile was developed and validated for the determination of 78 steroids (groups I-V) in human urine. PMID- 26268572 TI - Optimizing Deep Brain Stimulation of the Nucleus Accumbens in a Reward Preference Rat Model. AB - OBJECTIVE/HYPOTHESIS: Deep brain stimulation (DBS) has become the preferred therapy for a growing number of treatment-resistant neuropsychiatric conditions, offering the benefit of being amenable to fine-tuning to enhance its efficacy. However, while some DBS parameters are routinely adjusted, the stimulation is almost always delivered in a continuous "tonic" pattern, which may be suboptimal at times. Our overall aim is to investigate the application of differing levels of rewarding DBS to the reconditioning of behavioral "trigger" and "non-trigger" stimuli in impulse-control disorders (including addiction). As a first step, we used a rat model of nucleus accumbens (NAc) DBS to rigorously compare the relative reward values of different stimulation paradigms. We hypothesized that delivering pulses in a more physiological pattern would prove more rewarding than delivering tonic stimulation. MATERIALS AND METHODS: We implanted microelectrodes in the left NAc shell and trained rats to initiate and terminate DBS to demonstrate their "preference" between different brain stimulation reward (BSR) paradigms. We tested a range of BSR paradigms, including tonic, intermittent tonic, and burst paradigms. Two paradigms were compared at a time, and paired t tests were used to determine whether the rats significantly "preferred" one paradigm over another. RESULTS: The rats significantly preferred intermittent tonic BSR paradigms to continuous and burst paradigms, and generally preferred paradigms that delivered more pulses over the stimulation period. CONCLUSIONS: These findings highlight that the standard approach of delivering tonic DBS is not optimal under all circumstances. Further research should investigate which DBS paradigms are best for different brain disorders. PMID- 26268573 TI - Thiorhodococcus fuscus sp. nov., isolated from a lagoon. AB - A brown, moderately halophilic, photoautotrophic bacterium designated strain JA363T was purified from a photoheterotrophic enrichment obtained from sediment from Chilika lagoon, Odisha, India. Cells of the isolate were coccoid, motile by means of single polar flagellum and Gram-stain-negative. Strain JA363T had an obligate requirement for NaCl and could tolerate up to 7 % (w/v) NaCl. Strain JA363T had complex growth factor requirements. Internal photosynthetic membranes were present as vesicles. Strain JA363T contained bacteriochlorophyll a and spirilloxanthin series carotenoids with rhodopin as a major (>85 %) component. C16 : 1omega7c/C16 : 1omega6c, C18 : 1omega7c and C16 : 0 were the major fatty acids and phosphatidylglycerol and phosphatidylethanolamine were the major polar lipids. Q8 was the predominant quinone system of strain JA363T. The DNA G+C content was 64 mol%. The highest 16S rRNA gene sequence similarity of strain JA363T was found with the type strains of Thiorhodococcus kakinadensis (98.7 %), Thiohalobacter thiocyanaticus (98.2 %), Thiophaeococcus fuscus (97.4 %) and Thiorhodococcus bheemlicus (96.3 %). However, the phylogenetic trees generated firmly placed strain JA363T in the genus Thiorhodococcus, which was further supported by phenotypic and chemotaxonomic evidence. Consequently, strain JA363T is described as representing a novel species of the genus Thiorhodococcus as Thiorhodococcus fuscus sp. nov. The type strain is JA363T ( = KCTC 5701T = NBRC 104959T). PMID- 26268574 TI - Borrowing to save: can NHS bodies ease financial pressures by terminating PFI contracts? PMID- 26268575 TI - Triplex DNA: A new platform for polymerase chain reaction-based biosensor. AB - Non-specific PCR amplification and DNA contamination usually accompany with PCR process, to overcome these problems, here we establish a sensor for thrombin by sequence-specific recognition of the PCR product with molecular beacon through triplex formation. Probe A and probe B were designed for the sensor, upon addition of thrombin, two probes hybridized to each other and the probe B was extended in the presence of Klenow Fragment polymerase and dNTPs. The PCR amplification occurred with further addition of Taq DNA Polymerase and two primers, the PCR product was recognized by molecular beacon through triplex formation. The fluorescence intensity increased with the logarithm of the concentration of thrombin over the range from 1.0 * 10(-12) M to 1.0 * 10(-7) M, with a detection limit of 261 fM. Moreover, the effect of DNA contamination and non - specific amplification could be ignored completely in the proposed strategy. PMID- 26268576 TI - A systematic review of the magnitude and cause of geographic variation in unplanned hospital admission rates and length of stay for ambulatory care sensitive conditions. AB - BACKGROUND: Unplanned hospital admissions place a large and increasing strain on healthcare budgets worldwide. Many admissions for ambulatory care sensitive conditions (ACSCs) are thought to be preventable, a belief supported by significant geographic variations in admission rates. We conducted a systematic review of the evidence on the magnitude and correlates of geographic variation in ACSC admission rates and length of stay (LOS). METHODS: We performed a search of Medline and Embase databases for English language cross-sectional and cohort studies on 28th March 2013 reporting geographic variation in admission rates or LOS for patients receiving unplanned care across at least 10 geographical units for one of 35 previously defined ACSCs. Forward and backward citation searches were undertaken on all included studies. We provide a narrative synthesis of study findings. Study quality was assessed using a modified Newcastle-Ottawa scale. RESULTS: We included 39 studies comprising 25 on admission rates and 14 on LOS. Studies generally compared admission rates between regions (e.g. states) and LOS between hospitals. Most of the published research was undertaken in the US, UK or Canada and often focussed on patients with pneumonia, COPD or heart failure. 35 (90%) studies concluded that geographic variation was present. Primary care quality and secondary care access were frequently suggested as drivers of admission rate variation whilst secondary care quality and adherence to clinical guidelines were often listed as contributors to LOS variation. Several different methods were used to quantify variation, some studies listed raw data, failed to control for confounders and used naive statistical methods which limited their utility. CONCLUSIONS: The substantial geographical variations in the admission rates and LOS of potentially avoidable conditions could be a symptom of variable quality of care and should be a concern for clinicians and policymakers. Policymakers targeting a reduction in unplanned admissions could introduce initiatives to improve primary care access and quality or develop alternatives to admission. Those attempting to curb unnecessarily long LOS could introduce care pathways or guidelines. Methodological work on the quantification and reporting of geographic variation is needed to aid inter-study comparisons. PMID- 26268577 TI - Media Coverage of Pediatric Environmental Health Risks and its Effects on Mothers' Protective Behaviors. AB - This study explores the relationship between exposure to U.S. media coverage of chemical threats to pediatric environmental health and mothers' behaviors to protect their children. Prior content analytic work revealed that media coverage volume from September 2012 to February 2013 differed significantly by type of chemical (i.e., pesticides = high coverage volume; bisphenol A [BPA] = moderate; and arsenic = low). Survey data collected from new and expecting mothers in March 2013 (n = 822) revealed mothers incidentally encountered-or scanned-this information in the media in the prior six months, and after adjusting for a series of potential confounders, such scanning was positively associated with mothers' self-reported behaviors to reduce chemical exposures. To test the hypothesis that coverage volume moderates the relationship between scanning and behavior, content analysis and survey data were combined in mixed effects regression analyses. Results showed significant differences between the effects of media scanning at different levels of coverage volume, but in a direction not entirely consistent with the study's hypothesis. The relationship between scanning and behavior was strongest for BPA, suggesting that a characteristic of media coverage other than volume may drive maternal responses to environmental health threats. Implications of these findings for risk communication research and practice are discussed. PMID- 26268578 TI - Factors associated with knowledge of personal gestational weight gain recommendations. AB - OBJECTIVES: Excess adiposity (obesity and excess gestational weight gain, GWG) during pregnancy (EADP) increases risk for gestational diabetes, preeclampsia, and child and maternal obesity. Personal GWG goals predict total GWG. Some estimates suggest only 30% of pregnant women have personal GWG goals that are congruent with Institute of Medicine GWG recommendations. The primary purpose of this study was to determine the extent to which perceived pre-pregnancy weight status, healthcare provider advice, knowledge of EADP risks, and value for healthy GWG predicted knowledge of GWG recommendations. The secondary purpose was to determine sources of GWG information among pregnant women. METHODS: Pregnant women with a confirmed singleton pregnancy completed a one-time survey in obstetric clinic waiting rooms. Logistic regression analysis was used. RESULTS: 246 predominantly African American, low income, overweight/obese women completed surveys. Average age was 25 (SD 5.3) and gestation age ranged from 7 to 40 weeks. Knowledge of pre-pregnancy weight status was the only unique predictor of GWG recommendation knowledge (B = .642, p = .03). The top three sources of GWG information were physicians, internet, and books. The least frequently reported sources of GWG information were other healthcare providers, community programs, and television. CONCLUSION: In low income diverse overweight/obese pregnant women, accurate pre-pregnancy weight status perception was the only significant unique predictor of knowledge of GWG recommendations. Physicians were the preferred source of GWG information. Clinicians should have frequent, ongoing conversations about weight status with women before, during, and after pregnancy. PMID- 26268579 TI - The relationship between proton pump inhibitor use and serum magnesium concentration among hemodialysis patients: a cross-sectional study. AB - BACKGROUND: Observational data suggest that serum magnesium (Mg) concentration is inversely related to vascular calcification and hyperparathyroidism among patients with end-stage renal disease (ESRD). In recent years, there have been several case reports of hypomagnesemia due to use of proton-pump inhibitors (PPI), with the hypomagnesemia attributed to inappropriate gastrointestinal (GI) Mg loss. We hypothesized that the tendency to GI Mg loss is more common than is currently reported. Since patients with ESRD have little to no renal Mg loss to affect serum Mg concentration, dialysis patients are an interesting population in whom to study the relationship between PPI use and serum Mg levels. METHODS: Using a single-center cross-sectional design, we studied 155 prevalent hemodialysis (HD) patients. Serum Mg concentration for each patient was determined based on the mean of 3 consecutive serum Mg levels drawn at 6 week intervals. PPI use at the time of the blood tests was documented. The relationship between PPI use and Mg concentration was determined in unadjusted analyses, as well as after adjustment for age, gender, race, cause of ESRD, diabetes, time on HD and dialysate Mg concentration. RESULTS: 55 % of patients were on PPIs at the time of the study. The majority of patients (62 %) used a dialysate Mg (in mmol/L) of 0.5, and the remainder (38 %) used a dialysate Mg of 0.375. Serum Mg levels were significantly lower among PPI users vs. non-users (0.93 vs. 1.02 mmol/L, p < 0.001). This finding persisted after stratifying for dialysate Mg concentration, and after multivariable adjustment (p < 0.001). In addition, more PPI users vs. non-users had a Mg level < 1 mmol/L (79 % vs. 43 %) and a Mg level < 0.8 mmol/L (16 % vs. 4 %). There was a non-significant trend toward increased time on PPI being associated with lower serum Mg levels (p = 0.067). CONCLUSION: Among HD patients, PPI users have lower serum Mg levels as compared with non-users. Further research is required to determine whether the magnitude of change in Mg levels among PPI users is associated with adverse outcomes. PMID- 26268580 TI - Portability of the thiolation domain in recombinant pyoverdine non-ribosomal peptide synthetases. AB - BACKGROUND: Non-ribosomal peptide synthetase (NRPS) enzymes govern the assembly of amino acids and related monomers into peptide-like natural products. A key goal of the field is to develop methods to effective recombine NRPS domains or modules, and thereby generate modified or entirely novel products. We previously showed that substitution of the condensation (C) and adenylation (A) domains in module 2 of the pyoverdine synthetase PvdD from Pseudomonas aeruginosa led to synthesis of modified pyoverdines in a minority of cases, but that more often the recombinant enzymes were non-functional. One possible explanation was that the majority of introduced C domains were unable to effectively communicate with the thiolation (T) domain immediately upstream, in the first module of PvdD. RESULTS: To test this we first compared the effectiveness of C-A domain substitution relative to T-C-A domain substitution using three different paired sets of domains. Having previously demonstrated that the PvdD A/T domain interfaces are tolerant of domain substitution, we hypothesised that T-C-A domain substitution would lead to more functional recombinant enzymes, by maintaining native T/C domain interactions. Although we successfully generated two recombinant pyoverdines, having a serine or a N5-formyl-N5-hydroxyornithine residue in place of the terminal threonine of wild type pyoverdine, in neither case did the T-C-A domain substitution strategy lead to substantially higher product yield. To more comprehensively examine the abilities of non-native T domains to communicate effectively with the C domain of PvdD module 2 we then substituted the module 1 T domain with 18 different T domains sourced from other pyoverdine NRPS enzymes. In 15/18 cases the recombinant NRPS was functional, including 6/6 cases where the introduced T domain was located upstream of a C domain in its native context. CONCLUSIONS: Our data indicate that T domains are generally able to interact effectively with non-native C domains, contrasting with previous findings that they are not generally portable upstream of epimerisation (E) or thioesterase (TE) domains. This offers promise for NRPS recombination efforts, but also raises the possibility that some C domains are unable to efficiently accept non-native peptides at their donor site due to steric constraints or other limitations. PMID- 26268581 TI - Foundations for evidence-based intraoperative neurophysiological monitoring. AB - In this review, we recommend means to enhance the evidence-base for intraoperative neurophysiological monitoring (IONM). We address two preliminary issues: (1) whether IONM should be evaluated as a diagnostic test or an intervention, and (2) the state of the evidence for IONM (as presented in systematic reviews, for example). Three reasons may be suggested to evaluate at least some IONM applications as interventions (or as part of an "interventional cascade"). First, practical barriers limit our ability to measure IONM diagnostic accuracy. Second, IONM results are designed to be correlated with interventions during surgery. Third, IONM should improve patient outcomes when IONM-directed intervention alters the course of surgery. Observational evidence for IONM is growing yet more is required to understand the conditions under which IONM, in its variety of settings, can benefit patients. A multi-center observational cohort study would represent an important initial compromise between the pragmatic difficulties with conducting controlled trials in IONM and the Evidence Based Medicine (EBM) view that large scale randomized trials are required. Such a cohort study would improve the evidence base and (if justified) provide the rationale for controlled trials. PMID- 26268582 TI - An Autopsy Case of Acute Massive Hematochezia Caused by Superior Mesenteric Vein Thrombosis: A First Report in Forensic Medicine. AB - Superior mesenteric vein thrombosis (SMVT) is an uncommon cause of intestinal ischemia and massive gastrointestinal bleeding. This report describes a man with alcoholic liver cirrhosis, who died of massive hematochezia due to SMVT. A medicolegal autopsy disclosed a thrombus at the superior mesenteric vein and hemorrhagic infarction of the bowel wall, an area also within the territory of the superior mesenteric vein. Liver cirrhosis, an enlarged spleen, and esophageal varices without rupture were also observed, but ulcers and variceal bleeding were not. Other organs showed no significant findings. His blood alcohol level was 0.14% w/v. Thus, this man died from severe hematochezia associated with SMVT due to liver cirrhosis and alcohol dehydration, which can lead to coagulopathy and rapid progress of thrombus formation. This is the first report on an alternate cause for massive gastrointestinal hemorrhage with a cirrhotic patient in a forensic autopsy. PMID- 26268583 TI - Intralesional epidermal growth factor for diabetic foot wounds: the first cases in Turkey. AB - BACKGROUND: Intralesional recombinant epidermal growth factor (EGF) was produced in the Centre for Genetic Engineering and Biotechnology (CIGB), Cuba, in 1988 and licensed in 2006. Because it may accelerate wound healing, it is a potential new treatment option in patients with a diabetic foot wound (whether infected or not) as an adjunct to standard treatment (i.e. debridement, antibiotics). We conducted the initial evaluation of EGF for diabetic foot wounds in Turkey. METHODS: We enrolled 17 patients who were hospitalized in various medical centers for a foot ulcer and/or infection and for whom below the knee amputation was suggested to all except one. All patients received 75 MUg intralesional EGF three times per week on alternate days. RESULTS: The appearance of new granulation tissue on the wound site (>=75%) was observed in 13 patients (76%), and complete wound closure was observed in 3 patients (18%), yielding a 'complete recovery' rate of 94%. The most common side effects were tremor (n=10, 59%) and nausea (n=6, 35%). In only one case,a serious side effect requiring cessation of EGF treatment was noted. That patient experienced severe hypotension at the 16th application session, and treatment was discontinued. At baseline, a total of 21 causative bacteria were isolated from 15 patients, whereascultures were sterile in two patients. The most frequently isolated species was Pseudomonas aeruginosa. CONCLUSION: Thus, this preliminary study suggests that EGF seems to be a potential adjunctive treatment option in patients with limb-threatening diabetic foot wounds. PMID- 26268584 TI - Combination of three angiogenic growth factors has synergistic effects on sprouting of endothelial cell/mesenchymal stem cell-based spheroids in a 3D matrix. AB - Combinations of angiogenic growth factors have been shown to have synergistic effects on angiogenesis and natural wound healing in various animal models. Each growth factor has unique roles during angiogenesis; vascular endothelial growth factor (VEGF) plays a key role during the initial step of angiogenesis, whereas PDGF functions in the maturation of blood vessels. We used a combination of three angiogenic growth factors to increase angiogenesis in vitro and in vivo. We chose VEGF as a basic factor and added platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) to induce angiogenesis in three in vitro and in vivo models: 3D angiogenesis assay, 3D co-culture, and matrigel plug implantation assay. Cell proliferation was significantly higher in co-cultured cells treated with PDGF + VEGF + FGF than in the control, single, or dual combination groups. mRNA expression of alpha-smooth muscle actin (alpha-SMA), von Willebrand factor (vWF), and CD105 was higher in the triple group (PDGF + VEGF + FGF) than in control, single, or dual combination groups. In the PDGF + VEGF + FGF group, the length and number of branches of spheroids was also significantly higher than in the control, single, or dual combination groups. Furthermore, in a nude mouse model, alpha-SMA expression was significantly higher in the PDGF + VEGF + FGF group than in other groups. In conclusion, the addition of PDGF and FGF to VEGF showed synergistic effects on angiogenesis in vitro and in vivo. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1535-1543, 2016. PMID- 26268585 TI - The role of evidence analysts in creating nutrition management guidelines for inherited metabolic disorders. AB - RATIONALE, AIMS AND OBJECTIVES: Evidence and consensus-based guidelines for nutrition management of maple syrup urine disease (MSUD) were developed as part of a project to create nutrition guidelines for inherited metabolic disorders identified through newborn screening. The objective of this study was to describe and evaluate the role of evidence analysts in the systematic review phase of guideline development to improve quality of process and output and inform future guideline development projects. METHODS: Recruitment, training and output of evidence analysts were documented throughout the MSUD project. The role of analysts was to critically review and rate the scientific quality of published literature and abstract pertinent information using quality checklists and abstraction worksheets. A secure, web-based application was developed to standardize the process and establish permanent documentation. Analysts completed a post-project survey on perceptions of their role, training and the evidence analysis process. RESULTS: Of 23 recruits, 65% (15) completed evidence analyst training; 73% of those (11) participated in the analysis of 98 literature articles. Analysts reviewed a median of four articles (range 1-16) with median productivity of 1.1 articles per month. All analysts surveyed (n = 9) understood their role and agreed that training was adequate; 100% agreed that analyst involvement was critical in developing guidelines for MSUD. CONCLUSION: Evidence analysts played a key role in appraising and abstracting evidence to develop nutrition guidelines for MSUD. With critical improvements to the process, particularly more stringent and systematic evaluation and documentation of analyst performance related to productivity and quality, we will continue to recruit, train and support evidence analysts in evidence-based guideline development projects. PMID- 26268586 TI - Laboratory Validation of Two Wearable Sensor Systems for Measuring Head Impact Severity in Football Players. AB - Wearable sensors can measure head impact frequency and magnitude in football players. Our goal was to quantify the impact detection rate and validity of the direction and peak kinematics of two wearable sensors: a helmet system (HITS) and a mouthguard system (X2). Using a linear impactor, modified Hybrid-III headform and one helmet model, we conducted 16 impacts for each system at 12 helmet sites and 5 speeds (3.6-11.2 m/s) (N = 896 tests). Peak linear and angular accelerations (PLA, PAA), head injury criteria (HIC) and impact directions from each device were compared to reference sensors in the headform. Both sensors detected ~96% of impacts. Median angular errors for impact directions were 34 degrees for HITS and 16 degrees for X2. PLA, PAA and HIC were simultaneously valid at 2 sites for HITS (side, oblique) and one site for X2 (side). At least one kinematic parameter was valid at 2 and 7 other sites for HITS and X2 respectively. Median relative errors for PLA were 7% for HITS and -7% for X2. Although sensor validity may differ for other helmets and headforms, our analyses show that data generated by these two sensors need careful interpretation. PMID- 26268587 TI - Obesity and perioperative complications in head and neck free tissue reconstruction. AB - BACKGROUND: Free tissue transfer is a mainstay in reconstruction of complex head and neck defects. The purpose of this study was to determine if perioperative complications were more common in patients with body mass index (BMI) >30 kg/m(2) undergoing free flap reconstruction. METHODS: A multi-institutional retrospective cohort was created. Medical complications, surgical complications, and procedural variables were recorded. Logistic regression was used to investigate univariate and multivariate associations between outcomes and predictors. RESULTS: Of 582 cases, 128 patients (22%) had BMI >30. Surgical complications occurred in 153 cases (26.3%), with an adjusted odds ratio (OR) for association of surgical complications with BMI >30 of 0.92 (p = .71). Medical complications occurred in 178 cases (30.6%), with an adjusted OR of 0.78 (p = .26). Age and advanced comorbidity status (Adult Comorbidity Evaluation-27 [ACE-27] 2 or 3) were associated with medical complications (p < .0001). CONCLUSION: BMI >30 does not predict medical or surgical complications in patients undergoing head and neck free flap surgery. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1188-E1191, 2016. PMID- 26268588 TI - How much do rheumatologists and orthopaedists doctors' modalities impact the cost of arthritis in Cyprus? AB - BACKGROUND: Osteoarthritis is one of the primary causes of long-term functional disability. With an estimated 13.5% prevalence in the general population contributes to a significant financial burden both for patients and healthcare systems. The purpose of this research is to highlight the direct annual cost of the disease to the private healthcare sector of Nicosia. METHODS: A questionnaire based on Greek and international research was completed between 10/1/2012 and 11/30/2012, with a sample of 20 doctors specialists in orthopaedics and rheumatology (50% of practising physicians in the private sector). An assessment of the annual cost of medical procedures and tests, pharmacologic therapies (modalities) and supplies per patient followed, based on current costs. Direct costs were assessed through the micro-costing "bottom-up" approach. We isolated and separately priced the original diagnosis, followed by each stage of the disease. RESULTS: The cost for the six predominant medical tests to establish a diagnosis and exclude mainly RA such as ESR, CPR, and X-ray as well as a physician's office visit was 150? per patient. The average direct cost per patient during stages 1, 2 and 3 of the disease was 280.54?, 1,834.64? and 5,641.72? annually, respectively, with an annual average of 2,573? per patient. CONCLUSIONS: Even though during the period of the study, the country had not yet established clinical guidelines, the participating physicians followed international practices. Significant rise in the cost in each stage of the disease was found, with additional increases in the following years as a result of the expected increased prevalence of the disease. It is noted here that uninsured patients, as well as those who qualified for free medical care, they seek these services in the private sector, and had to pay out of pocket money for examination and treatment. These patients, thus, contended with a serious financial burden. Therefore, it is important to inform them very extensively regarding evidence-based management of the disease to aid them in coping with this chronic illness. PMID- 26268590 TI - Review article: Potential of medical scribes to allay the burden of documentation and enhance efficiency in Australian emergency departments. AB - The increasing burden of documentation experienced by doctors threatens the efficiency in EDs and increases the likelihood of documentation errors. Medical scribes afford the opportunity to allay this burden by removing a large component of the doctors' documentation task. Scribes have been embedded successfully in US EDs, and the effects have been mostly advantageous. The present paper provides a brief overview of the function of scribes and their potential contribution to Australian EDs. PMID- 26268589 TI - Contribution of Fe3O4 nanoparticles to the fouling of ultrafiltration with coagulation pre-treatment. AB - A coagulation (FeCl3)-ultrafiltration process was used to treat two different raw waters with/without the presence of Fe3O4 nanoparticle contaminants. The existence of Fe3O4 nanoparticles in the raw water was found to increase both irreversible and reversible membrane fouling. The trans-membrane pressure (TMP) increase was similar in the early stages of the membrane runs for both raw waters, while it increased rapidly after about 15 days in the raw water with Fe3O4 nanoparticles, suggesting the involvement of biological effects. Enhanced microbial activity with the presence of Fe3O4 nanoparticles was evident from the measured concentrations of extracellular polymeric substances (EPS) and deoxyribonucleic acid (DNA), and fluorescence intensities. It is speculated that Fe3O4 nanoparticles accumulated in the cake layer and increased bacterial growth. Associated with the bacterial growth is the production of EPS which enhances the bonding with, and between, the coagulant flocs; EPS together with smaller sizes of the nano-scale primary particles of the Fe3O4-CUF cake layer, led to the formation of a lower porosity, more resilient cake layer and membrane pore blockage. PMID- 26268591 TI - Proteome analysis of retinal glia cells-related inflammatory cytokines in the aqueous humour of diabetic patients. AB - PURPOSE: Retinal glia cells (RGC) activation and release of inflammatory cytokines have been associated with development of diabetic retinopathy (DR). In this study, we evaluated by protein array the presence of aqueous humour (AH) cytokines secreted by RGC in patients with diabetes without DR and with mild DR. METHODS: This is a cross-sectional, case-control study. Thirty-five subjects (diabetics and controls) underwent full ophthalmic examination and AH samples collection before cataract surgery at the Department of Ophthalmology University of Padova. AH samples were analysed for total protein concentration (Bradford method) and RGC-related inflammatory cytokines using glass chip protein arrays. RESULTS: Twelve diabetic patients without DR, 11 diabetic patients with mild DR and 12 non-diabetic controls were included. There was no significant difference in total protein concentration among the 3 groups. Interleukin IL-1beta, IL-3, interferon gamma (IFN-gamma), (IFN-gamma)-induced protein (IP)-10 and monocyte chemotactic protein (MCP)-2 were significantly increased in diabetics versus controls. IFN-gamma, IL-1alpha, IL-3 and MCP-2 were significantly increased in diabetics without DR versus controls, whereas granulocyte-macrophage colony stimulating factor (GM-CSF), IFN-gamma, IL-10, IP-10, regulated and normal T cell expressed and secreted (RANTES), and soluble tumour necrosis factor receptor (sTNF-R)II were significantly increased in diabetics with mild DR versus controls. Macrophage inflammatory protein (MIP-1beta), GMCSF, RANTES and sTNF-RII were significantly increased in diabetics with mild DR versus diabetics without DR (p < 0.05 at least for all). CONCLUSIONS: Differences in expression profile of AH cytokines between diabetics, without and with mild DR, and controls have been documented. Retinal neuroinflammatory biomarkers of RGC activation evaluated in AH by protein array analysis could guide in detecting specific phenotypes with potential for personalized management. PMID- 26268592 TI - Novel zinc finger transcription factor ZFP580 promotes differentiation of bone marrow-derived endothelial progenitor cells into endothelial cells via eNOS/NO pathway. AB - BACKGROUND: The differentiation of endothelial progenitor cells (EPCs) plays a pivotal role in endothelial repair and re-endothelialization after vascular injury. However, the underlying mechanisms still remain largely elusive. Here, we investigated the role of the novel C2H2 zinc finger transcription factor ZFP580 in EPC differentiation and the molecular mechanisms behind EPC-mediated endothelial repair. METHODS: Bone marrow-derived EPCs were isolated, cultured, and identified. EPCs were infected with an adenovirus encoding ZFP580 or Ad-siRNA to silence ZFP580. Fluorescence-activated cell sorting (FACS) analysis was performed to analyze EPC surface makers. The expression of ZFP580, eNOS, VEGFR-2, CD31, CD34, CD45 and vWF was performed by Q-PCR, Western blot and immunostaining. NO donor SNAP or NOS inhibitor L-NAME was used to elucidate the possible molecular mechanism. Tube formation in vitro and angiogenesis assay in vivo were also used in this study. RESULTS: Both ZFP580 and eNOS were displayed dynamic expression during EPC differentiation. Overexpression of ZFP580 enhanced EPC differentiation, while knockdown suppressed it. ZFP580 also enhanced eNOS expression, and eNOS inhibition suppressed differentiation. Upregulation/knockdown of ZFP580 also enhanced/reduced endothelial tube formation from EPC in vitro, and angiogenesis in vivo in response to Matrigel plugs containing EPC. CONCLUSIONS: ZFP580 promotes not only the differentiation of EPCs into ECs by increasing the expression of eNOS and the availability of nitric oxide, but also the vessel formation in vitro and in vivo. This might represent a novel mechanism of ZFP580 in EPC differentiation and its therapeutic value in the treatment of vascular disease. PMID- 26268593 TI - Comprehensive assessment of chamber-specific and transmural heterogeneity in myofilament protein phosphorylation by top-down mass spectrometry. AB - The heart is characterized by a remarkable degree of heterogeneity, the basis of which is a subject of active investigation. Myofilament protein post translational modifications (PTMs) represent a critical mechanism regulating cardiac contractility, and emerging evidence shows that pathological cardiac conditions induce contractile heterogeneity that correlates with transmural variations in the modification status of myofilament proteins. Nevertheless, whether there exists basal heterogeneity in myofilament protein PTMs in the heart remains unclear. Here we have systematically assessed chamber-specific and transmural variations in myofilament protein PTMs, specifically, the phosphorylation of cardiac troponin I (cTnI), cardiac troponin T (cTnT), tropomyosin (Tpm), and myosin light chain 2 (MLC2). We show that the phosphorylation of cTnI and alphaTm vary in the different chambers of the heart, whereas the phosphorylation of MLC2 and cTnT does not. In contrast, no significant transmural differences were observed in the phosphorylation of any of the myofilament proteins analyzed. These results highlight the importance of appropriate tissue sampling-particularly for studies aimed at elucidating disease mechanisms and biomarker discovery-in order to minimize potential variations arising from basal heterogeneity in myofilament PTMs in the heart. PMID- 26268594 TI - LRRK2 Facilitates tau Phosphorylation through Strong Interaction with tau and cdk5. AB - Leucine-rich repeat kinase 2 (LRRK2) and tau have been identified as risk factors of Parkinson's disease (PD). As LRRK2 is a kinase and tau is hyperphosphorylated in some LRRK2 mutation carriers of PD patients, the obvious hypothesis is that tau could be a substrate of LRRK2. Previous reports that LRRK2 phosphorylates free tau or tubulin-associated tau provide direct support for this proposition. By comparing LRRK2 with cdk5, we show that wild-type LRRK2 and the G2019S mutant phosphorylate free recombinant full-length tau protein with specific activity 480 and 250-fold lower than cdk5, respectively. More strikingly tau binds to wt LRRK2 or the G2019S mutant 140- or 200-fold more strongly than cdk5. The extremely low activity of LRRK2 but strong binding affinity with tau suggests that LRRK2 may facilitate tau phosphorylation as a scaffold protein rather than as a major tau kinase. This hypothesis is further supported by the observation that (i) cdk5 or tau coimmunoprecipitates with endogenous LRRK2 in SH-SY5Y cells, in mouse brain tissue, and in human PBMCs; (ii) knocking down endogenous LRRK2 by its siRNA in SH-SY5Y cells reduces tau phosphorylation at Ser396 and Ser404; (iii) inhibiting LRRK2 kinase activity by its inhibitors has no effect on tau phosphorylation at these two sites; and (iv) overexpressing wt LRRK2, the G2019S mutant, or the D1994A kinase-dead mutant in SH-SY5Y cells has no effect on tau phosphorylation. Our results suggest that LRRK2 facilitates tau phosphorylation indirectly by recruiting tau or cdk5 rather than by directly phosphorylating tau. PMID- 26268595 TI - [Development of an action scale to show the necessity of healthcare activities]. AB - OBJECTIVES: In order to promote high-quality healthcare activities, public health professionals such as public health nurses must improve their ability to systematically show health needs based on evidence and to lead decision making of superior officers and facility inhabitants for improved planning. This study developed and investigated its reliability and validity of an action scale to show the necessity of healthcare activities (SNH). METHODS: The items in the SNH were originally selected based on previous studies and refined by researchers; they were subsequently adjusted after a pilot survey. The subjects were full-time public health nurses (PHNs) working at prefectural public health centers or randomly chosen municipal health centers. Questionnaires were distributed by mail. We explained the ethical considerations in writing and those who returned completed questionnaire forms were considered to have given their consent to participate in the study. The study plan was approved by the university Domestic Ethics Committee. RESULTS: Among 1,615 questionnaire recipients, 1,088 (67.4%) responded; of these, 1,035 (64.1%) responses were valid. Nineteen of 20 items were selected based on results of item analysis, and exploratory and confirmatory factor analyses showed that the SNH consisted of four factors: show existence of health needs, show evidence for the necessity of addressing health needs, show actual conditions requiring solution, and show priority for resolution. Cronbach's alpha, an SNH reliability coefficient, was 0.948, and individual factor scores were over 0.85, supporting the internal consistency of SNH. The correlation coefficient between SNH and the three other scales including related concepts was 0.6-0.8, with significant differences between scales, supporting the criterion-related validity of SNH. The score increased with increasing PHN experience and job seniority, which were used as the known-group, with significant differences between the lowest group and the top two groups. CONCLUSION: The results confirmed that SNH is a reliable and valid scale to show the necessity of healthcare activities. PMID- 26268596 TI - [An initiative to develop a new employment support facility for older job seekers in metropolitan areas]. AB - OBJECTIVES: This study examined the possibility and necessity for expansion and diffusion of a new employment support facility for older job seekers in metropolitan areas based on health and welfare measures. This longitudinal study assessed questionnaire responses from older job seekers at a new facility established in Ota ward in the Tokyo metropolitan area as a compliment to the conventional system comprised of Hello Work and the Silver Human Resources Center. METHODS: We offered questionnaires to job seekers at their first facility visit and asked them to return them by mail (baseline survey). Follow-up surveys of the same respondents were conducted after 2, 4, 8, and 12 weeks, with questions about demographics, personal status, social activities, mental health, and job search status. The surveys were administered from January 2013 to March 2014. RESULTS: We obtained 128 responses (average respondent age: 63.8 years) from 180 baseline survey questionnaires. The respondents included 82 males and 46 females. The response rates were over 90% for all follow-up surveys. Among respondents, 71.4% had less than a senior high school level of education. The average annual household income was less than 3 million yen and less than 1 million yen for 68.0% and 16.0% of the participants, respectively. The life circumstances were "hard" or "very hard" for 56.3% of respondents. Among respondents, 78.9% indicated that they were seeking employment for economic reasons. Women and those over 65 years of age were more likely to search for jobs for their well-being than men and respondents less than 65 years of age. The majority of respondents indicated that they wanted to make use of their abilities or experience and many hoped to work as garbage collectors, cooks, or apartment caretakers. CONCLUSION: We found that the main objective of older job seekers living at this facility was economic acquisition. Men and those less than 65 years of age were at particular risk for economic distress, poor mental health, and were more likely to be searching for regular employment. A relatively higher proportion of women and respondents over 65 years of age were seeking jobs for their well-being; a need for social relationships that may be more pronounced among women in this study population. PMID- 26268597 TI - [The effects of oral health ordinances and legislation promoting dental and oral health on community-based dental and oral health organizations]. PMID- 26268598 TI - [Research on mental health and welfare activities in municipalities]. PMID- 26268599 TI - Lamina Cribrosa-Related Parameters Assessed by Optical Coherence Tomography for Prediction of Future Glaucoma Progression. AB - PURPOSE: To evaluate the value of lamina cribrosa (LC)-related parameters assessed by optical coherence tomography (OCT) in the future prediction of glaucomatous progression. METHODS: Glaucoma or glaucoma suspect eyes were followed up for more than 2 years. Glaucoma progression was defined by optic disc/retinal nerve fiber layer (RNFL) photographic assessment or serial visual field exams. LC thickness, anterior LC distance (ALD) and prelaminar tissue thicknesses were determined with optic disc images obtained by Spectralis OCT enhanced depth imaging. Kaplan-Meier life table analyses were carried out, and survival experience was compared between eyes with thicker baseline LC (HLC) and thinner baseline LC (LLC) by a log rank test. Hazard ratios (HRs) of various risk factors, including LC-related parameters, for future glaucomatous progression, were determined using uni- and multi-variate Cox's proportional hazard models. RESULTS: Among the 118 eyes, 33 showed progression during follow-up period. The progression group had a significantly thinner average circumpapillary RNFL (cRNFL, p = 0.005), LC (p = 0.005) and prelaminar tissue (p = 0.023) than the non progression group at baseline. The LLC group showed a greater cumulative probability of glaucoma progression than did the HLC group (p = 0.001). Average cRNFL thickness (HR, 0.972, p = 0.007), prelaminar tissue thickness (0.990, p = 0.028) and LC thickness (0.971, p = 0.002) were significantly associated with progression of glaucoma. In multivariate analysis, only LC thickness (0.975, p = 0.015) showed significant association with progression. CONCLUSION: Thinner baseline LC was independently associated with glaucoma progression in our study. LC thickness may be a risk factor for predicting future glaucoma progression. PMID- 26268600 TI - Air classification: Potential treatment method for optimized recycling or utilization of fine-grained air pollution control residues obtained from dry off gas cleaning high-temperature processing systems. AB - In the dust collected from the off-gas of high-temperature processes, usually components that are volatile at the process temperature are enriched. In the recycling of the dust, the concentration of these volatile components is frequently limited to avoid operation problems. Also, for external utilization the concentration of such volatile components, especially heavy metals, is often restricted. The concentration of the volatile components is usually higher in the fine fractions of the collected dust. Therefore, air classification is a potential treatment method to deplete the coarse material from these volatile components by splitting off a fines fraction with an increased concentration of those volatile components. In this work, the procedure of a sequential classification using a laboratory air classifier and the calculations required for the evaluation of air classification for a certain application were demonstrated by taking the example of a fly ash sample from a biomass combustion plant. In the investigated example, the Pb content in the coarse fraction could be reduced to 60% by separation of 20% fines. For the non-volatile Mg the content was almost constant. It can be concluded that air classification is an appropriate method for the treatment of off-gas cleaning residues. PMID- 26268601 TI - Healthcare waste management research: A structured analysis and review (2005 2014). AB - The importance of healthcare waste management in preserving the environment and protecting the public cannot be denied. Past research has dealt with various issues in healthcare waste management and disposal, which spreads over various journals, pipeline research disciplines and research communities. Hence, this article analyses this scattered knowledge in a systematic manner, considering the period between January 2005 and July 2014. The purpose of this study is to: (i) identify the trends in healthcare waste management literature regarding journals published; (ii) main topics of research in healthcare waste management; (iii) methodologies used in healthcare waste management research; (iv) areas most frequently researched by researchers; and (v) determine the scope of future research in healthcare waste management. To this end, the authors conducted a systematic review of 176 articles on healthcare waste management taken from the following eight esteemed journals: International Journal of Environmental Health Research, International Journal of Healthcare Quality Assurance, Journal of Environmental Management, Journal of Hazardous Material, Journal of Material Cycles and Waste Management, Resources, Conservations and Recycling, Waste Management, and Waste Management & Research. The authors have applied both quantitative and qualitative approaches for analysis, and results will be useful in the following ways: (i) results will show importance of healthcare waste management in healthcare operations; (ii) findings will give a comparative view of the various publications; (c) study will shed light on future research areas. PMID- 26268602 TI - Assessment of quality and relevance of curricula development in health training institutions: a case study of Kenya. AB - The World Health Organization lists Kenya among African countries experiencing health workforce crisis catalysed through immigration, underproduction, inconsistent quality of production and unequal distribution. Strengthening health training institutions to increase production of high-quality health workers is acknowledged as a measure to mitigate the crisis.IntraHealth International's USAID-funded FUNZOKenya Project (2012-2017) undertook an assessment to identify the bottlenecks to increasing the number and quality of pre-service graduates in Kenya. The assessment, a cross-sectional descriptive study, collected data through structured respondent interviews among faculty, students in health training institutions, key informants and desk review. The assessment purposively selected 14 institutions from 18 institutions identified for initial collaboration with the project towards strengthening health workforce training. The statistical package for social sciences (SPSS) application helped analyse quantitative data and quotes used to illustrate perceptions on the quality of curricula.The findings revealed major gaps in quality and adequacy of curricula in the training institutions. A national standard framework to guide curricula review process is lacking. Further, curricula did not adequately prepare students for clinical placement, as most failed to directly respond to national health needs. The study recommended reviews of curricula to ensure their responsiveness to emerging issues in the health sector, the formation of curriculum committees to review curricula, development of official curricula review standards and an integrated mechanism to disseminate policies and guidelines. PMID- 26268604 TI - Silver-Mediated Oxidative Trifluoromethylation of Phenols: Direct Synthesis of Aryl Trifluoromethyl Ethers. AB - Aryl trifluoromethyl ethers (ArOCF3 ) are prevalent in pharmaceuticals, agrochemicals, and materials. However, methods for the general and efficient synthesis of these compounds are extremely underdeveloped and limited. Herein, we describe a highly efficient and general procedure for the direct O trifluoromethylation of unprotected phenols through a silver-mediated cross coupling reaction using CF3 SiMe3 as the CF3 source and exogenous oxidants. This novel oxidative trifluoromethylation provides access to a wide range of aryl trifluoromethyl ethers from simple phenols. The mild process was also applied to the late-stage trifluoromethylation of a medicinally relevant compound. PMID- 26268603 TI - Polymorphisms in sweet taste genes (TAS1R2 and GLUT2), sweet liking, and dental caries prevalence in an adult Italian population. AB - The aim of the study was to assess the relationship between sweet taste genes and dental caries prevalence in a large sample of adults. In addition, the association between sweet liking and sugar intake with dental caries was investigated. Caries was measured by the decayed, missing, filled teeth (DMFT) index in 647 Caucasian subjects (285 males and 362 females, aged 18-65 years), coming from six villages in northeastern Italy. Sweet liking was assessed using a 9-point scale, and the mean of the liking given by each individual to specific sweet food and beverages was used to create a sweet liking score. Simple sugar consumption was estimated by a dietary history interview, considering both added sugars and sugar present naturally in foods. Our study confirmed that polymorphisms in TAS1R2 and GLUT2 genes are related to DMFT index. In particular, GG homozygous individuals for rs3935570 in TAS1R2 gene (p value = 0.0117) and GG homozygous individuals for rs1499821 in GLUT2 gene (p value = 0.0273) showed higher DMFT levels compared to both heterozygous and homozygous for the alternative allele. Furthermore, while the relationship sugar intake-DMFT did not achieve statistical significance (p value = 0.075), a significant association was identified between sweet liking and DMFT (p value = 0.004), independent of other variables. Our study showed that sweet taste genetic factors contribute to caries prevalence and highlighted the role of sweet liking as a predictor of caries risk. Therefore, these results may open new perspectives for individual risk identification and implementation of target preventive strategies, such as identifying high-risk patients before caries development. PMID- 26268605 TI - Use of complementary and alternative medicine within Norwegian hospitals. AB - BACKGROUND: Over the recent decades complementary and alternative medicine (CAM) use within and outside of the public health care system in Norway has increased. The aim of this study is to describe to what extent CAM is offered in Norwegian hospitals in 2013 and investigate possible changes since 2008. METHODS: In January 2013 a one-page questionnaire was sent to the medical director of all included hospitals (n = 80). He/she was asked to report whether or not one or more specific CAM therapies were offered in the hospital. Fifty-nine (73.8%) hospitals responded and form the basis for the analyses. RESULTS: CAM was offered in 64.4% of the responding hospitals. No major differences were found between public and private, or between somatic and psychiatric, hospitals. Acupuncture was the most frequent CAM method offered, followed by art- and expression therapy and massage. The proportion of hospitals offering CAM has increased from 50.5% in 2008 to 64.4% in 2013 (p = 0.089). The largest increase was found in psychiatric hospitals where 76.5% of hospitals offered CAM in 2013 compared to 28.6% in 2008 (p = 0.003). A small decrease was found in the proportion of hospitals offering acupuncture between 2008 (41.4%) and 2013 (37.3%). CONCLUSIONS: A majority of Norwegian hospitals offer some sort of CAM. The largest increase since 2008 was found in psychiatric hospitals. Psychiatric hospitals seem to have established a practice of offering CAM to their patients similar to the practice in somatic hospitals. This could indicate a shift in the attitude with regard to CAM in psychiatric hospitals. PMID- 26268606 TI - Analysis of archived residual newborn screening blood spots after whole genome amplification. AB - BACKGROUND: Deidentified newborn screening bloodspot samples (NBS) represent a valuable potential resource for genomic research if impediments to whole exome sequencing of NBS deoxyribonucleic acid (DNA), including the small amount of genomic DNA in NBS material, can be overcome. For instance, genomic analysis of NBS could be used to define allele frequencies of disease-associated variants in local populations, or to conduct prospective or retrospective studies relating genomic variation to disease emergence in pediatric populations over time. In this study, we compared the recovery of variant calls from exome sequences of amplified NBS genomic DNA to variant calls from exome sequencing of non-amplified NBS DNA from the same individuals. RESULTS: Using a standard alignment-based Genome Analysis Toolkit (GATK), we find 62,000-76,000 additional variants in amplified samples. After application of a unique kmer enumeration and variant detection method (RUFUS), only 38,000-47,000 additional variants are observed in amplified gDNA. This result suggests that roughly half of the amplification introduced variants identified using GATK may be the result of mapping errors and read misalignment. CONCLUSIONS: Our results show that it is possible to obtain informative, high-quality data from exome analysis of whole genome amplified NBS with the important caveat that different data generation and analysis methods can affect variant detection accuracy, and the concordance of variant calls in whole genome amplified and non-amplified exomes. PMID- 26268607 TI - HDL-bound sphingosine 1-phosphate acts as a biased agonist for the endothelial cell receptor S1P1 to limit vascular inflammation. AB - The sphingosine 1-phosphate receptor 1 (S1P1) is abundant in endothelial cells, where it regulates vascular development and microvascular barrier function. In investigating the role of endothelial cell S1P1 in adult mice, we found that the endothelial S1P1 signal was enhanced in regions of the arterial vasculature experiencing inflammation. The abundance of proinflammatory adhesion proteins, such as ICAM-1, was enhanced in mice with endothelial cell-specific deletion of S1pr1 and suppressed in mice with endothelial cell-specific overexpression of S1pr1, suggesting a protective function of S1P1 in vascular disease. The chaperones ApoM(+)HDL (HDL) or albumin bind to sphingosine 1-phosphate (S1P) in the circulation; therefore, we tested the effects of S1P bound to each chaperone on S1P1 signaling in cultured human umbilical vein endothelial cells (HUVECs). Exposure of HUVECs to ApoM(+)HDL-S1P, but not to albumin-S1P, promoted the formation of a cell surface S1P1-beta-arrestin 2 complex and attenuated the ability of the proinflammatory cytokine TNFalpha to activate NF-kappaB and increase ICAM-1 abundance. Although S1P bound to either chaperone induced MAPK activation, albumin-S1P triggered greater Gi activation and receptor endocytosis. Endothelial cell-specific deletion of S1pr1 in the hypercholesterolemic Apoe(-/-) mouse model of atherosclerosis enhanced atherosclerotic lesion formation in the descending aorta. We propose that the ability of ApoM(+)HDL to act as a biased agonist on S1P1 inhibits vascular inflammation, which may partially explain the cardiovascular protective functions of HDL. PMID- 26268609 TI - The rhodopsin-guanylyl cyclase of the aquatic fungus Blastocladiella emersonii enables fast optical control of cGMP signaling. AB - Blastocladiomycota fungi form motile zoospores that are guided by sensory photoreceptors to areas of optimal light conditions. We showed that the microbial rhodopsin of Blastocladiella emersonii is a rhodopsin-guanylyl cyclase (RhGC), a member of a previously uncharacterized rhodopsin class of light-activated enzymes that generate the second messenger cyclic guanosine monophosphate (cGMP). Upon application of a short light flash, recombinant RhGC converted within 8 ms into a signaling state with blue-shifted absorption from which the dark state recovered within 100 ms. When expressed in Xenopus oocytes, Chinese hamster ovary cells, or mammalian neurons, RhGC generated cGMP in response to green light in a light dose dependent manner on a subsecond time scale. Thus, we propose RhGC as a versatile tool for the optogenetic analysis of cGMP-dependent signaling processes in cell biology and the neurosciences. PMID- 26268608 TI - Survivin promotes oxidative phosphorylation, subcellular mitochondrial repositioning, and tumor cell invasion. AB - Survivin promotes cell division and suppresses apoptosis in many human cancers, and increased abundance correlates with metastasis and poor prognosis. We showed that a pool of survivin that localized to the mitochondria of certain tumor cell lines enhanced the stability of oxidative phosphorylation complex II, which promoted cellular respiration. Survivin also supported the subcellular trafficking of mitochondria to the cortical cytoskeleton of tumor cells, which was associated with increased membrane ruffling, increased focal adhesion complex turnover, and increased tumor cell migration and invasion in cultured cells, and enhanced metastatic dissemination in vivo. Therefore, we found that mitochondrial respiration enhanced by survivin contributes to cancer metabolism, and relocalized mitochondria may provide a "regional" energy source to fuel tumor cell invasion and metastasis. PMID- 26268610 TI - Simultaneous quantitative determination of multiple bioactive markers in Ocimum sanctum obtained from different locations and its marketed herbal formulations using UPLC-ESI-MS/MS combined with principal component analysis. AB - INTRODUCTION: Ocimum sanctum L., with phenolic acids, flavonoids, propenyl phenols and terpenoids as active pharmacological constituents, is a popular medicinal herb and is present as an ingredient in many herbal formulations. Therefore, development of a reliable analytical method for simultaneous determination of the pharmacologically active constituents of O. sanctum is of high importance. OBJECTIVE: To develop and validate a new, rapid, sensitive and selective UPLC-ESI/MS/MS method for simultaneous determination of 23 bioactive markers including phenolic acids, flavonoids, propenyl phenol and terpenoid in the leaf extract and marketed herbal formulations of O. sanctum. METHODS: An UPLC ESI/MS/MS method using negative electrospray ionisation (ESI) in multiple reaction-monitoring (MRM) mode was used for simultaneous determination. Chromatographic separation was achieved on an Acquity UPLC BEH C18 -column using a gradient elution with 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Principal component analysis (PCA) was applied to correlate and discriminate eight geographical collections of O. sanctum based on quantitative data of the analytes. RESULTS: The developed method was validated as per International Conference on Harmonization guidelines and found to be accurate, with overall recovery in the range 95.09-104.84% (RSD <= 1.85%), precise (RSD <= 1.98%) and linear (r(2) >= 0.9971) over the concentration range of 0.5-1000 ng/mL. Ursolic acid was found to be the most abundant marker in all the samples investigated, except for the marketed tablet. CONCLUSION: The method established is simple, rapid and sensitive, hence it can be reliably utilised for the quality control of O. sanctum and derived herbal formulations. PMID- 26268611 TI - Polarity-tunable magnetic tunnel junctions based on ferromagnetism at oxide heterointerfaces. AB - Complex oxide systems have attracted considerable attention because of their fascinating properties, including the magnetic ordering at the conducting interface between two band insulators, such as LaAlO3 and SrTiO3. However, the manipulation of the spin degree of freedom at the LaAlO3/SrTiO3 heterointerface has remained elusive. Here, we have fabricated hybrid magnetic tunnel junctions consisting of Co and LaAlO3/SrTiO3 ferromagnets with the insertion of a Ti layer in between, which clearly exhibit magnetic switching and the tunnelling magnetoresistance effect below 10 K. The magnitude and sign of the tunnelling magnetoresistance are strongly dependent on the direction of the rotational magnetic field parallel to the LaAlO3/SrTiO3 plane, which is attributed to a strong Rashba-type spin-orbit coupling in the LaAlO3/SrTiO3 heterostructure. Our study provides a further support for the existence of the macroscopic ferromagnetism at LaAlO3/SrTiO3 heterointerfaces and opens a novel route to realize interfacial spintronics devices. PMID- 26268612 TI - Viscoelastic deformation of lipid bilayer vesicles. AB - Lipid bilayers form the boundaries of the cell and its organelles. Many physiological processes, such as cell movement and division, involve bending and folding of the bilayer at high curvatures. Currently, bending of the bilayer is treated as an elastic deformation, such that its stress-strain response is independent of the rate at which bending strain is applied. We present here the first direct measurement of viscoelastic response in a lipid bilayer vesicle. We used a dual-beam optical trap (DBOT) to stretch 1-palmitoyl-2-oleoyl-sn-glycero-3 phosphocholine (POPC) giant unilamellar vesicles (GUVs). Upon application of a step optical force, the vesicle membrane deforms in two regimes: a fast, instantaneous area increase, followed by a much slower stretching to an eventual plateau deformation. From measurements of dozens of GUVs, the average time constant of the slower stretching response was 0.225 +/- 0.033 s (standard deviation, SD). Increasing the fluid viscosity did not affect the observed time constant. We performed a set of experiments to rule out heating by laser absorption as a cause of the transient behavior. Thus, we demonstrate here that the bending deformation of lipid bilayer membranes should be treated as viscoelastic. PMID- 26268613 TI - Diffractive microscopy in dermatopathology. AB - Diffraction is the process by which a beam of light is spread out as a result of passing through a narrow aperture or across an edge. Light diffraction can be produced by closing the aperture diaphragm beyond the recommended setting, by flipping the condenser cone down, or by using an opaque object such as the microscopist's hand to block the column of light and force it to bend around the edge. Any of these techniques results in greater refractility of objects in the path of the light. We studied 77 biopsy specimens from a variety of conditions selected to compare the value of diffractive microscopy, and found that it worked best in the evaluation of alopecia, tumor stroma, hemosiderin, argyria and imipramine pigmentation. In amyloidosis stained with Congo red and silica granuloma, polarized microscopy was superior to diffraction microscopy, and neither diffractive microscopy nor polarized microscopy was superior to routine light microscopy in the evaluation of melanin, chrysiasis or ochronosis. PMID- 26268614 TI - The genetic architecture of petal number in Cardamine hirsuta. AB - Invariant petal number is a characteristic of most flowers and is generally robust to genetic and environmental variation. We took advantage of the natural variation found in Cardamine hirsuta petal number to investigate the genetic basis of this trait in a case where robustness was lost during evolution. We used quantitative trait locus (QTL) analysis to characterize the genetic architecture of petal number. Alphaverage petal number showed transgressive variation from zero to four petals in five C. hirsuta mapping populations, and this variation was highly heritable. We detected 15 QTL at which allelic variation affected petal number. The effects of these QTL were relatively small in comparison with alleles induced by mutagenesis, suggesting that natural selection may act to maintain petal number within its variable range below four. Petal number showed a temporal trend during plant ageing, as did sepal trichome number, and multi-trait QTL analysis revealed that these age-dependent traits share a common genetic basis. Our results demonstrate that petal number is determined by many genes of small effect, some of which are age-dependent, and suggests a mechanism of trait evolution via the release of cryptic variation. PMID- 26268615 TI - Percutaneous closure of post TAVR LV apical pseudoaneurysm. AB - Left ventricular (LV) apical pseudoaneurysm is a well known complication of myocardial infarction and open heart surgery procedures, and has more recently been described after transapical transcatheter aortic valve replacement (TAVR). Since the natural history includes a high incidence of cardiac rupture and mortality in the 30-45% range within the first year after diagnosis, surgical repair has been the main therapy. More recently, LV pseudoaneurysms have been closed using percutaneous methods. We describe a post-TAVR pseudoaneurysm for which closure was done via retrograde LV access using a vascular plug, and provide a review of recent literature on closure methods and outcomes. (c) 2015 Wiley Periodicals, Inc. PMID- 26268616 TI - Characterization of early changes in fetoplacental hemodynamics in a diet-induced rabbit model of IUGR. AB - Intrauterine growth restriction (IUGR) is associated with adverse perinatal outcomes and late-onset diseases in offspring. Eating disorders, voluntary caloric restriction and maternal undernutrition can all induce IUGR but a relevant model is required to measure all its possible consequences. In this work, pregnant rabbits were used as an IUGR model. Control females (n=4) received ad libitum diet throughout pregnancy, whereas underfed females (n=5) were restricted to 50% of their daily requirements. Offspring size was measured by ultrasonography and in vivo at birth. Hemodynamic features of the umbilical cords and middle cerebral arteries (systolic peak velocity, end diastolic velocity, pulsatility index and resistance index) were characterized by Doppler ultrasonography. At day 21, maternal underfeeding resulted in a significant reduction of fetal size (occipito-nasal length). At birth, the size of kits from the underfed group was significantly lower (lower crown-rump length, biparietal and transversal thoracic diameters) and a reduced weight with respect to the control group. Feed restriction altered blood flow perfusion compared with does fed ad libitum (significant higher systolic peak, time-averaged mean velocities and lower end diastolic velocity). Fetuses affected by IUGR presented with compensative brain-sparing effects when compared with the control group. In conclusion, the present study supports using rabbits and the underfeeding approach as a valuable model for IUGR studies. These results may help to characterize IUGR alterations due to nutrient restriction of mothers in future research. PMID- 26268617 TI - An Evidence-Based Systematic Review of Beta-Sitosterol, Sitosterol (22,23- dihydrostigmasterol, 24-ethylcholesterol) by the Natural Standard Research Collaboration. AB - An evidence-based systematic review of beta-sitosterol, sitosterol (22,23 dihydrostigmasterol, 24-ethylcholesterol) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing. PMID- 26268618 TI - Deleterious effects of skin freezing contribute to variable outcomes of the predictive drug permeation studies using hydrophilic molecules. PMID- 26268620 TI - Study on preparation method of Zanthoxylum bungeanum seeds kernel oil with zero trans-fatty acids. AB - The seed of Zanthoxylum bungeanum (Z. bungeanum) is a by-product of pepper production and rich in unsaturated fatty acid, cellulose, and protein. The seed oil obtained from traditional producing process by squeezing or extracting would be bad quality and could not be used as edible oil. In this paper, a new preparation method of Z. bungeanum seed kernel oil (ZSKO) was developed by comparing the advantages and disadvantages of alkali saponification-cold squeezing, alkali saponification-solvent extraction, and alkali saponification supercritical fluid extraction with carbon dioxide (SFE-CO2). The results showed that the alkali saponification-cold squeezing could be the optimal preparation method of ZSKO, which contained the following steps: Z. bungeanum seed was pretreated by alkali saponification under the conditions of adding 10 %NaOH (w/w), solution temperature was 80 degrees C, and saponification reaction time was 45 min, and pretreated seed was separated by filtering, water washing, and overnight drying at 50 degrees C, then repeated squeezing was taken until no oil generated at 60 degrees C with 15 % moisture content, and ZSKO was attained finally using centrifuge. The produced ZSKO contained more than 90 % unsaturated fatty acids and no trans-fatty acids and be testified as a good edible oil with low-value level of acid and peroxide. It was demonstrated that the alkali saponification-cold squeezing process could be scaled up and applied to industrialized production of ZSKO. PMID- 26268619 TI - Analysis of connexin expression during seizures induced by 4-aminopyridine in the rat hippocampus. AB - BACKGROUND: In epilepsy, seizures are generated by abnormal synchronous activity in neurons. In the rat hippocampus (HIP), epileptiform activity has been found to be associated with gap junctions (GJs). GJs are formed by the combination of two hemichannels, each composed of six connexins. At low doses, the convulsive drug 4 aminopyridine (4-AP) produces epileptiform activity without affecting glutamate levels; therefore, GJs could participate in its effect. Based on this argument, in this study, the expression of Cx 32, Cx 36 and Cx 43 protein and mRNA in the HIP of rats treated with 4-AP was evaluated. The evaluation of connexins was carried out by chemifluorescent immunoassay, semiquantitative RT-PCR and immunofluorescence to detect the amount and distribution of connexins and of cellular markers in the HIP and dentate gyrus (DG) of animals treated with NaCl and 4-AP in the right entorhinal cortex. In these animals, convulsive behavior and EEG signals were analyzed. RESULTS: The animals treated with 4-AP showed convulsive behavior and epileptiform activity 60 min after the administration. A significant increase in the protein expression of Cx 32, Cx 36 and Cx 43 was found in the HIP contralateral and ipsilateral to the site of 4-AP administration. A trend toward an increase in the mRNA of Cx 32 and Cx 43 was also found. An increase in the cellular density of Cx 32 and Cx 43 was found in the right HIP and DG, and an increase in the cellular density of oligodendrocytes in the DG and a decrease in the number of cells marked with NeuN were observed in the left HIP. CONCLUSIONS: Cx 32 and Cx 43 associated with oligodendrocytes and astrocytes had an important role in the first stages of seizures induced by 4-AP, whereas Cx36 localized to neurons could be associated with later stages. Additionally, these results contribute to our understanding of the role of connexins in acute seizures and allow us to direct our efforts to other new anticonvulsant strategies for seizure treatment. PMID- 26268622 TI - Evaluation of dry deposition of acidifying N compounds to vegetation. AB - This papers deals with direct measurements of dry deposition flux of total acidifying N species (gaseous HNO3 and particulate NO3(-)) and theoretically by parameterization method to vegetation (leaf surfaces) over a semiarid region in India. Annual average experimental dry deposition of NO3(-) to leaf of Cassia is 0.65 +/- 0.61 mg m(-2) day(-1). Ambient concentrations of HNO3 vapor and particulate NO3(-) are 1.53 and 1.24 MUg m(-3), respectively. Theoretically obtained dry deposition velocity of HNO3 and NO3(-) are 0.74 cm s(-1) for both while calculated dry deposition flux of total NO3(-) is found to be 1.3 +/- 0.33 mg m(-2) day(-1). The measured dry deposition flux of NO3(-) to Cassia leaf is in the range of theoretically obtained flux. The annual input of N as nitrate is 3.8 mmol m(-2) year(-1) which is lower than the other forest site in China which is probably because of low pollution than China. PMID- 26268621 TI - Challenging synergistic activity of poplar-bacteria association for the Cd phytostabilization. AB - The synergistic activity between plants and microorganisms may contribute to the implementation of proactive management strategies in the stabilization of contaminated sites, although heavy metals, such as cadmium (Cd), are potentially toxic to them. The aim of this study was to evaluate the degree of tolerance to Cd contamination (supplying twice 40 mg kg(-1) of Cd) in poplar cuttings [clone I 214, P. * euramericana (Dode) Guinier] inoculated or not with two concentrations of Serratia marcescens strain (1 * 10(7) CFU/g and 2 * 10(7) CFU/g of potting mix). The response of the plant-bacteria system to excess Cd was investigated with special reference to the structural traits of plants and the functional efficiency of bacteria. Bacterial colonization and substrate components were previously assessed in order to define the best solution for formulating the experimental plant growth media. The tested plant-bacteria association, especially when bacteria were provided in double concentration, stimulated specific tolerance mechanisms to Cd through the promotion of the poplar growth. Inoculated plants produced larger leaves and increased stem diameter, while roots grew longer and wider in Cd-treated plants. The effect of bacterial inoculum on plant growth traits and metal partitioning in plant organs was assessed in order to define the potential of this poplar clone to be a suitable candidate for phytostabilization of Cd-contaminated soil. The final effect of the inoculation with bacteria, which alleviated the metal load and Cd phytotoxicity due to their bioaccumulation ability, suggests promising phytostabilization potential of these plant-bacteria associations. PMID- 26268623 TI - Effects of aeration and internal recycle flow on nitrous oxide emissions from a modified Ludzak-Ettinger process fed with glycerol. AB - Nitrous oxide (N2O) is emitted from a modified Ludzak-Ettinger (MLE) process, as a primary activated sludge system, which requires mitigation. The effects of aeration rates and internal recycle flow (IRF) ratios on N2O emission were investigated in an MLE process fed with glycerol. Reducing the aeration rate from 1.5 to 0.5 L/min increased gaseous the N2O concentration from the aerobic tank and the dissolved N2O concentration in the anoxic tank by 54.4 and 53.4 %, respectively. During the period of higher aeration, the N2O-N conversion ratio was 0.9 % and the potential N2O reducers were predominantly Rhodobacter, which accounted for 21.8 % of the total population. Increasing the IRF ratio from 3.6 to 7.2 decreased the N2O emission rate from the aerobic tank and the dissolved N2O concentration in the anoxic tank by 56 and 48 %, respectively. This study suggests effective N2O mitigation strategies for MLE systems. PMID- 26268624 TI - Heavy metal accumulation in soils, plants, and hair samples: an assessment of heavy metal exposure risks from the consumption of vegetables grown on soils previously irrigated with wastewater. AB - It is common knowledge that soils irrigated with wastewater accumulate heavy metals more than those irrigated with cleaner water sources. However, little is known on metal concentrations in soils and cultivars after the cessation of wastewater use. This study assessed the accumulation and health risk of heavy metals 3 years post-wastewater irrigation in soils, vegetables, and farmers' hair. Soils, vegetables, and hair samples were collected from villages previously irrigating with wastewater (experimental villages) and villages with no history of wastewater irrigation (control villages). Soil samples were digested in a mixture of HCL/HNO3/HCLO4/HF. Plants and hair samples were digested in HNO3/HCLO4 mixture. Inductive coupled plasma-optical emission spectrometer (ICP-OES) was used to determine metal concentrations of digested extracts. Study results indicate a persistence of heavy metal concentration in soils and plants from farms previously irrigated with wastewater. In addition, soils previously irrigated with wastewater were severely contaminated with cadmium. Hair metal concentrations of farmers previously irrigating with wastewater were significantly higher (P < 0.05) than farmers irrigating with clean water, but metal concentrations in hair samples of farmers previously irrigating with wastewater were not associated with current soil metal concentrations. The study concludes that there is a persistence of heavy metals in soils and plants previously irrigated with wastewater, but high metal concentrations in hair samples of farmers cannot be associated with current soil metal concentrations. PMID- 26268625 TI - Effect of the ultrasound-Fenton oxidation process with the addition of a chelating agent on the removal of petroleum-based contaminants from soil. AB - The effects of ultrasonic irradiation, the chelating agent modified Fenton reaction, and a combination of ultrasound and the Fenton method in removing petroleum contaminants from a soil were studied. The results showed that the contaminant removal rate of the Fenton treatment combined with an oxalic acid chelating agent was 55.6% higher than that without a chelating agent. The average removal rate of the contaminants using the ultrasound-Fenton treatment was 59.0% higher than that without ultrasonic treatment. A combination of ultrasound and an Fe(2+)/Fe(3+)-oxalate complex-modified Fenton reagent resulted in significantly higher removal rates of n-alkanes (C(n)H(2n+2), n < 28), isoprenoid hydrocarbons, aromatic hydrocarbons, and saturated polycyclic terpenes compared with the ultrasound treatment alone or the Fenton method. The Fenton reaction and the ultrasound-Fenton treatment can unselectively remove multiple components of residual hydrocarbons and a number of benzene rings in polycyclic aromatic hydrocarbons. The chemistry of the heterocyclic compounds and the position and number of substituents can affect the degradation process. PMID- 26268627 TI - What factors are associated with the prevalence of atopic symptoms amongst adolescents in Greater Manchester? AB - INTRODUCTION: Atopy commonly manifests itself as atopic diseases (ADs), namely asthma, eczema and hay fever. The prevalence of AD is rising worldwide, and it is widely accepted as a major public health issue, due to the significant burden of AD on health care systems. METHOD: Data were obtained from the youth survey of the European Urban Health Indicator System 2 project. The study participants were students aged 14-16 years from Greater Manchester. The main outcomes measured were the prevalence of atopic symptoms and the factors associated with the development of atopy. RESULTS: Of the sample studied, 70% reported having had an AD during their lifetime. The lifetime prevalence of ever having asthma, eczema or hay fever was 33.4%, 28.1% and 49.0%, respectively. Gender, family affluence, body mass index, diet, smoking and worrying were all significantly associated with atopic symptoms. Smoking was the only variable to be significantly associated with all three ADs. Season of birth and pollution were not shown to be associated with atopic symptoms. CONCLUSION: This study demonstrates that the prevalence of AD in Greater Manchester was high amongst adolescents. Several environmental, demographic and social factors were found to be significantly associated with the development of atopic symptoms. This study provides a baseline for future studies to further investigate the factors that are associated with AD and allow for the implementation of preventative public health policy. PMID- 26268626 TI - Strategies and techniques to enhance constructed wetland performance for sustainable wastewater treatment. AB - Constructed wetlands (CWs) have been used as an alternative to conventional technologies for wastewater treatment for more than five decades. Recently, the use of various modified CWs to improve treatment performance has also been reported in the literature. However, the available knowledge on various CW technologies considering the intensified and reliable removal of pollutants is still limited. Hence, this paper aims to provide an overview of the current development of CW strategies and techniques for enhanced wastewater treatment. Basic information on configurations and characteristics of different innovations was summarized. Then, overall treatment performance of those systems and their shortcomings were further discussed. Lastly, future perspectives were also identified for specialists to design more effective and sustainable CWs. This information is used to inspire some novel intensifying methodologies, and benefit the successful applications of potential CW technologies. PMID- 26268628 TI - Medication adherence among patients with chronic conditions in Italy. AB - BACKGROUND: The aims of the cross-sectional study were to measure the extent of adherence to prescribed medications among patients affected by chronic diseases and to identify the predictors of the adherence. METHODS: The study was conducted between March and December 2014 among 633 outpatients in four hospitals in Italy. Data were collected using a face to face interview at the time of their visit to the hospital. The Morisky Medication Adherence 4-item Scale was used to measure patients' self-reported adherence. RESULTS: The majority of the patients were male (51.7%), the mean age was 63.2 years, one-third had at least a high school diploma or equivalent, 34.6% was employed, and the main diseases were hypertension, diabetes, and chronic obstructive pulmonary disease. A total of 39.3% patients reported themselves as being adherent to medications over the 4 weeks preceding their medical specialist's visit. Patients were more likely to adhere to medications if they had a college degree or higher level of education, a higher score of the Katz index, took a lower number of total pills per day, and did not use pill organizers. Patients who have never forgotten to take medications over the 4 weeks preceding their medical specialist's visit were 46.1%. CONCLUSIONS: The findings emphasize the need for improving information for the individuals affected by chronic diseases concerning the risks of non adherence in order to encourage responsible behaviour to prescribed medications. PMID- 26268629 TI - A high energy intake from dietary fat among middle-aged and older adults is associated with increased risk of malnutrition 10 years later. AB - A higher fat content in the diet could be an advantage for preventing malnutrition among older adults. However, there is sparse scientific evidence to determine the optimal fat intake among older adults. This prospective cohort study examined whether a high energy intake of dietary fat among middle-aged and older adults is associated with the risk of malnutrition 10 years later. The study population comprised 725 Swedish men and women aged 53-80 years who had completed a questionnaire about dietary intake and lifestyle factors in 1997 (baseline) and whose nutritional status was assessed when admitted to the hospital in 2008-2009 (follow-up). At the follow-up, 383 (52.8%) participants were identified as being at risk of malnutrition and fifty-two (7.2%) were identified as malnourished. Multinomial logistic regression models were used to analyse the association between previous dietary fat intake and nutritional status later in life. Contrary to what was expected, a high energy intake from total fat, saturated fat and monounsaturated fat among middle-aged and older adults increased the risk of exhibiting malnutrition 10 years later. However, this applied only to individuals with a BMI<25 kg/m2 at the baseline. In conclusion, these findings suggest that preventive actions to counteract malnutrition in older adults should focus on limiting the intake of total fat in the diet by reducing consumption of food with a high content of saturated and monounsaturated fat. PMID- 26268631 TI - Background sounds and hearing-aid users: A scoping review. AB - OBJECTIVES: A scoping review focused on background sounds and adult hearing-aid users, including aspects of aversiveness and interference. The aim was to establish the current body of knowledge, identify knowledge gaps, and to suggest possible future directions for research. DESIGN: Data were gathered using a systematic search strategy, consistent with scoping review methodology. STUDY SAMPLE: Searches of public databases between 1988 and 2014 returned 1182 published records. After exclusions for duplicates and out-of- scope works, 75 records remained for further analysis. Content analysis was used to group the records into five separate themes. RESULTS: Content analysis indicated numerous themes relating to background sounds. Five broad emergent themes addressed the development and validation of outcome instruments, satisfaction surveys, assessments of hearing-aid technology and signal processing, acclimatization to the device post-fitting, and non-auditory influences on benefit and satisfaction. CONCLUSIONS: A large proportion of hearing-aid users still find particular hearing-aid features and attributes dissatisfying when listening in background sounds. Many conclusions are limited by methodological drawbacks in study design and too many different outcome instruments. Future research needs to address these issues, while controlling for hearing-aid fitting. PMID- 26268632 TI - Modification of hippocampal excitability in brain slices pretreated with a low nanomolar concentration of Zn2+. AB - Synaptic Zn2+ homeostasis may be changed during brain slice preparation. However, much less attention has been paid to Zn2+ in artificial cerebrospinal fluid (ACSF) used for slice experiments than has been paid to Ca2+ . The present study assesses addition of Zn2+ to ACSF, focused on hippocampal excitability after acute brain slice preparation. When the static levels of intracellular Zn2+ and Ca2+ were compared between brain slices prepared with conventional ACSF without Zn2+ and those pretreated with ACSF containing 20 nM ZnCl2 for 1 hr, both levels were almost the same. On the other hand, intracellular Ca2+ levels were significantly increased in the stratum lucidum of the control brain slices after stimulation with high K+, although the increase was significantly suppressed by the pretreatment with ACSF containing Zn2+, suggesting that neuronal excitation is enhanced in brain slices prepared with ACSF without Zn2+. The increase in extracellular Zn2+ level, an index of glutamate release, after stimulation with high K+ was also significantly suppressed by pretreatment with ACSF containing Zn2+. When mossy fiber excitation was assessed in brain slices with FM4-64, an indicator of presynaptic activity, attenuation of FM 4-64 fluorescence based on presynaptic activity was suppressed in the stratum lucidum of brain slices pretreated with ACSF containing Zn2+. The present study indicates that hippocampal excitability is enhanced in brain slices prepared with ACSF without Zn2+. It is likely that a low nanomolar concentration of Zn2+ is necessary for ACSF. PMID- 26268630 TI - A hepatic amino acid/mTOR/S6K-dependent signalling pathway modulates systemic lipid metabolism via neuronal signals. AB - Metabolism is coordinated among tissues and organs via neuronal signals. Levels of circulating amino acids (AAs), which are elevated in obesity, activate the intracellular target of rapamycin complex-1 (mTORC1)/S6kinase (S6K) pathway in the liver. Here we demonstrate that hepatic AA/mTORC1/S6K signalling modulates systemic lipid metabolism via a mechanism involving neuronal inter-tissue communication. Hepatic expression of an AA transporter, SNAT2, activates the mTORC1/S6K pathway, and markedly elevates serum triglycerides (TGs), while downregulating adipose lipoprotein lipase (LPL). Hepatic Rheb or active-S6K expression have similar metabolic effects, whereas hepatic expression of dominant negative-S6K inhibits TG elevation in SNAT2 mice. Denervation, pharmacological deafferentation and beta-blocker administration suppress obesity-related hypertriglyceridemia with adipose LPL upregulation, suggesting that signals are transduced between liver and adipose tissue via a neuronal pathway consisting of afferent vagal and efferent sympathetic nerves. Thus, the neuronal mechanism uncovered here serves to coordinate amino acid and lipid levels and contributes to the development of obesity-related hypertriglyceridemia. PMID- 26268635 TI - Elevated caspase 3 activity and cytosolic cytochrome c in NT2 cybrids containing amyotrophic lateral sclerosis subject mtDNA. AB - Apoptosis of motor neurons is an important feature in amyotrophic lateral sclerosis (ALS). A vital role of mitochondria in apoptosis and cell survival is well documented. Eventually mitochondria have shown to be an early target in the pathogenesis of ALS. On account of these facts, we investigated the involvement of mitochondrial-dependent apoptosis in ALS and control (CTR) cybrids, generated fusing human platelets with mitochondrial DNA-depleted NT2-neuroteratocarcinoma cells. After a 6 week selection process during which transferred subject mtDNA repopulated the NT2 cells and restored mitochondrial oxygen consumption, we assessed cell viability and two programmed cell death parameters, caspase 3 activity and cytosolic cytochrome c levels. Compared to the control cybrid lines (n = 5), the ALS cybrid lines (n = 10) showed 45% less XTT reduction and higher caspase 3 activity ( p < 0.05, two-way Student's t test) exhibiting lesser cell viability and execution of apoptosis. Elevated cytosolic cytochrome c levels in ALS cybrid lines (n = 8) than in CTR (n = 4) ( p < 0.05, two-way Student's t test) indicating its mitochondrial release and initiation of apoptosis. This indicates apoptosis as one of the possible mechanisms of cell death in ALS. Our findings support the view that in ALS, subject's mitochondria are altered in non degenerating tissues in such a way that intrinsic apoptotic pathway activity is relatively increased. PMID- 26268633 TI - Relationships between clinician-level attributes and fidelity-consistent and fidelity-inconsistent modifications to an evidence-based psychotherapy. AB - BACKGROUND: Clinicians often modify evidence-based psychotherapies (EBPs) when delivering them in routine care settings. There has been little study of factors associated with or implications of modifications to EBP protocols. This paper differentiates between fidelity-consistent and fidelity-inconsistent modifications and it examines the potential influence of two clinician characteristics, training outcomes, and attitudes toward EBPs on fidelity consistent and fidelity-inconsistent modifications of cognitive behavioral therapy in a sample of clinicians who had been trained to deliver these treatments for children or adults. METHODS: Survey and coded interview data collected 2 years after completion of training programs in cognitive behavioral therapy were used to examine associations between successful or unsuccessful completion of training, clinician attitudes, and modifications. Modifications endorsed by clinicians were categorized as fidelity-consistent or fidelity inconsistent and entered as outcomes into separate regression models, with training success and attitudes entered as independent variables. RESULTS: Successful completion of a training program was associated with subsequent fidelity-inconsistent modifications but not fidelity-consistent modifications. Therapists who reported greater openness to using EBPs prior to training reported more fidelity-consistent modifications at follow-up, and those who reported greater willingness to adopt EBPs if they found them appealing were more likely to make fidelity-inconsistent modifications. CONCLUSIONS: Implications of these findings for training, implementation, EBP sustainment, and future studies are discussed. Research on contextual and protocol-related factors that may impact decisions to modify EBPs will be an important future direction of study to complement to this research. PMID- 26268634 TI - Cannabis Mobile Apps: A Content Analysis. AB - BACKGROUND: Mobile technology is pervasive and widely used to obtain information about drugs such as cannabis, especially in a climate of rapidly changing cannabis policy; yet the content of available cannabis apps is largely unknown. Understanding the resources available to those searching for cannabis apps will clarify how this technology is being used to reflect and influence cannabis use behavior. OBJECTIVE: We investigated the content of 59 cannabis-related mobile apps for Apple and Android devices as of November 26, 2014. METHODS: The Apple and Google Play app stores were searched using the terms "cannabis" and "marijuana." Three trained coders classified the top 20 apps for each term and each store, using a coding guide. Apps were examined for the presence of 20 content codes derived by the researchers. RESULTS: Total apps available for each search term were 124 for cannabis and 218 for marijuana in the Apple App Store, and 250 each for cannabis and marijuana on Google Play. The top 20 apps in each category in each store were coded for 59 independent apps (30 Apple, 29 Google Play). The three most common content areas were cannabis strain classification (33.9%), facts about cannabis (20.3%), and games (20.3%). In the Apple App Store, most apps were free (77%), all were rated "17+" years, and the average user rating was 3.9/5 stars. The most popular apps provided cannabis strain classifications (50%), dispensary information (27%), or general facts about cannabis (27%). Only one app (3%) provided information or resources related to cannabis abuse, addiction, or treatment. On Google Play, most apps were free (93%), rated "high maturity" (79%), and the average user rating was 4.1/5. The most popular app types offered games (28%), phone utilities (eg, wallpaper, clock; 21%) and cannabis food recipes (21%); no apps addressed abuse, addiction, or treatment. CONCLUSIONS: Cannabis apps are generally free and highly rated. Apps were most often informational (facts, strain classification), or recreational (games), likely reflecting and influencing the growing acceptance of cannabis for medical and recreational purposes. Apps addressing addiction or cessation were underrepresented in the most popular cannabis mobile apps. Differences among apps for Apple and Android platforms likely reflect differences in the population of users, developer choice, and platform regulations. PMID- 26268636 TI - Efficacy and safety of two single-pill fixed-dose combinations of angiotensin II receptor blockers/calcium channel blockers in hypertensive patients (EXAMINER study). AB - BACKGROUND: There is some controversy regarding which single-pill fixed-dose combinations of angiotensin II type 1 receptor blockers (ARBs) and calcium channel blockers (CCBs) are effective at reducing blood pressure (BP). METHODS: Sixty hypertensive patients who received a single-pill fixed-dose combination of valsartan 80 mg/day and amlodipine 5 mg/day were enrolled (UMIN Registration 000013460). They were randomly divided into two treatment groups [single-pill fixed-dose combination therapy with valsartan 80 mg/day and amlodipine 5 mg/day (Val/Am group), or irbesartan 100 mg/day and amlodipine 5 mg/day (Irb/Am group)] and treated for 16 weeks. If the patient did not reach the target office BP at 8 weeks, they received double doses of amlodipine (10 mg/day). RESULTS: In the Irb/Am group, systolic BP (SBP) and diastolic BP (DBP) were significantly decreased at 16 weeks. There were no significant changes in SBP or DBP in the Val/Am group. In the Irb/Am group, serum uric acid (UA) was significantly decreased at 8 weeks and patients who had hyperuricemia showed significantly decreased serum UA at 16 weeks. In addition, the levels of triglycerides (TG) were significantly decreased at 16 weeks in the Irb/Am group. CONCLUSION: A single-pill fixed-dose combination therapy with irbesartan 100 mg/day and amlodipine 5 mg/day was superior to the combination of valsartan 80 mg/day and amlodipine 5 mg/day with respect to significant decreases in BP, serum UA and TG in patients with hypertension. PMID- 26268637 TI - [Pay attention to the corneal epithelial cell dysfunction after cataract surgery]. AB - Corneal epithelial dysfunction ( CED ) is the abnormality of the regeneration, conjunction, adhesion and immigration of the corneal epithelium cells without the decompensation of the corneal limbal cells. Due to the affection resulting from the systemic problems of patients and the management in the preoperative period, some of the patients at one to two weeks after cataract surgery will present the edema and fluorescein staining of the corneal epithelium. Without correct therapy, the defect of the epithelium, or even persisting ulceration of the cornea will occur. The key points of the management for CED are the early diagnosis and reasonable therapy. We suggest paying special attention to CED in the patients with metabolism diseases, abnormality of the tear film and long-term blepharitis. PMID- 26268638 TI - [Clinical analyses of 21 cases of Thygeson's superficial punctate keratitis]. AB - OBJECTIVE: To study the clinical features, diagnosis and treatment of Thygeson's superficial punctate keratitis (TSPK). METHODS: Twenty-one cases diagnosed as TSPK between June 2010 and July 2013 were retrospectively analyzed, including clinical manifestation, characteristics of morphological changes imaged by laser confocal microscopy, treatment and therapeutic effects. RESULTS: All the 21 cases had the same presentation. Slit lamp examination showed several rough punctate intraepithelial opacities, which were usually slightly above the niveau of the surrounding epithelium. No cases had conjunctival congestions. Eight eyes of five patients with TSPK were imaged with a laser confocal biomicroscope. Clusters of highly reflective dots were revealed in the epithelium. The number of Langerhans cells was greatly increased in the basal cell layer of the focal corneal epithelium and the Bowman's layer in ten eyes affected by TSPK. The density of the subepithelial nerve plexus decreased. Some keratocytes had highly reflective cell bodies of irregular size, orientation, and shape in the anterior stroma in the affected eyes. After treatment with low concentration steroid eye drops and antiviral drugs, punctate opacities in all 21 cases were completely absorbed, leaving no scar, and the cure rate was 100%. But TSPK recurred in four cases. All recurrent cases were cured completely after treatment. CONCLUSIONS: Thygeson's superficial punctate keratitis is a kind of chronic recurrent superficial keratitis, without conjunctivitis. Confocal microscopic images have certain specificity, help diagnose and contribute to its pathogenesis research. Local use of low concentration steroid eye drops combined with antiviral drugs is effective for TSPK. Clinicians should pay attention to recurrence of TSPK. PMID- 26268639 TI - [Observation of orthokeratology discontinuation]. AB - OBJECTIVE: To observe the change of teenagers with short-time and long-time orthokeratology discontinuation, including diopters, corneal curvature, corneal topography, axial length, and central corneal thickness, and to investigate the refractive correction methods after long-time orthokeratology discontinuation. METHODS: Retrospective study. A total of 141 patients (257 eyes) with a history of wearing and discontinuing wearing orthokeratology lenses in our center were collected. According to the spherical equivalent diopters, the patients were divided into two groups (< or = -4.00 D for group I and -4.00 D for group II). Each group was further divided into two sub-groups by the discontinuation time (1 to 3 months for sub-group A and more than 3 months for sub-group B). Four sub groups were named as I A, II A, I B, and II B. Some optical examinations were performed for the patients before orthokeratology lens wearing and after orthokeratology discontinuation, such as refraction, corneal curvature, corneal topography, corneal endothelial cells, axial length, and central corneal thickness measurement. The refractive correction methods used by patients who had long-term orthokeratology discontinuation were recorded. The observed data were analyzed with paired t-test and one-way ANOVA by SPSS16. RESULTS: The statistically significant changes (t = 3.222, 3.404, 3.141, 5.012, P < 0.05) of spherical diopter values were (-0.31 +/- 0.58) D, (-0.48 +/- 0.68) D, (-0.35 +/- 0.65) D, and (-0.57 +/- 0.58) D for groups IA, IB, IIA, and IIB, respectively. astigmatism of the four sub-groups had no significant change (P > 0.05) The average annual spherical growth was (-0.08 +/- 0.17) D, (-0.12 +/- 0.17) D, ( 0.07 +/- 0.19) D, and (-0.15 +/- 0.16) D, respectively, for the four sub-groups, and there was no statistically significant difference among them (F = 1.180, P > 0.05). Compared to the state before wearing orthokeratology lenses, the corneal curvature measured by an autorefractor was statistically different for groups I A and I A, but not statistically different for groups I B and II B. For the long time discontinuation groups, only the SRI of the corneal topography had a statistically significant decrease compared to the value before wearing orthokeratology lenses, and others had no significant change. The average annual increase of axial length was (0.22 +/- 0.16) mm and (0.16 +/- 0.10) mm for groups IA and IB, respectively, and the increase was statistically significant (P < 0.05), but there was no significant difference between the two sub-groups (F = 1.908, P > 0.05). The central corneal thickness had no significant change (t = 1.971, 2.017, P > 0.05). The rates of the refractive correction methods after long-time discontinuation were 36.7%, 22.4%, 22.4%, 12.4%, and 6.1% for spectacles, rigid gas permeable contact lenses, soft contact lenses, either spectacles or soft contact lenses, and refractive operations, respectively. CONCLUSION: The corneal morphology and central corneal thickness returned to the original after three months of discontinuation of orthokeratology. The myopia had no significant growth after discontinuation, and there was no significant difference between low to moderate and relatively high myopia. PMID- 26268640 TI - [Corneal epithelial changes of soft contact lens wearers under a transmission electron microscope]. AB - OBJECTIVE: To investigate the difference in corneal epithelium between patients with and without soft contact lens (SCL) wearing, and to analyze corneal epithelial changes of the eyes with long-time SCL wearing. METHODS: In this cross sectional study, the subjects were divided into two groups: 13 patients of daily SCL wearers and 11 control subjects who had never worn contact lenses. The flap of corneal epithelium was observed by transmission electron microscopy. The corneal epithelial microvillus density was compared between the two groups. RESULTS: Transmission electron micrographs of the control group showed a tight connection between cells, regularly aligned basal cells, and continuous basement membrane. Compared with the control group, SCL wearers showed incomplete basement membrane, swollen epithelial cells, swollen mitochondria, and widened intercellular interstices. The density of corneal epithelium microvilli [(0.071466 +/- 0.015889)/microm2 vs. (0.139851 +/- 0.024171)/micro2] was lower (t = 8.312, P < 0.05). CONCLUSION: Long-term SCL wearing can induce remarkable changes of corneal epithelial tissue, and the density of corneal epithelial microvilli decreases. PMID- 26268641 TI - [Comparison of corneal nerve regeneration and dry eye condition after conventional LASIK and femtosecond-assisted LASIK]. AB - OBJECTIVE: To compare the regeneration of subbasal epithelial nerve plexus in the central cornea and dry eye condition between patients undergoing conventional LASIK surgery and femtosecond-assisted LASIK surgery. METHODS: It was across sectional study. Thirty patients (60 eyes) who had LASIK at our hospital from October 2011 to September 2012 were included in this study. Patients were divided into conventional LASIK group and femtosecond-assisted LASIK group based on the method used for corneal flap creation. Subjective and objective dry eye tests were carried out at 1 year after surgery. HRT III confocal microscopy was used to observe the regeneration of subbasal epithelial nerve plexus, and the images were analyzed by ACCMetrics software using quantitative parameters to determine the density and morphology of corneal nerve fibers. The data of corneal nerve fibers and dry eye condition in the two groups undergoing different LASIK procedures was compared using an independent sample t test. RESULTS: During the one-year postoperative follow-up, the Schirmer test result, tear film break-up time value, and ocular surface disease index score in the F-LASIK group [(12.65 +/- 8.73) mm/5min, (7.85 +/- 2.81) s, (7.25 +/- 6.35) points] were not significantly different from that in the C-LASIK group [(6.73 +/- 10.55) mm/ 5 min, (8.77 +/- 3.04) s, (4.46 +/- 5.37) points] (t =1.399, -1.050, -1.613, P > 0.05). Regarding the nerve fiber measurements, which included corneal nerve fiber density, corneal nerve branch density, corneal nerve fiber length, corneal total branch node, corneal nerve fiber width, and corneal nerve fiber tortuosit, there was no statistically significant difference in their results between patients who had femtosecond-assisted LASIK surgery [(16.46 +/- 6.65 )/mm2, (19.27 +/- 9.56)/mm2, (10.88 +/- 4.70) mm/mm2, (65.10 +/- 38.43)/mm2, (4.76 +/- 0.34) microm, (2.30 +/- 0.34) grades] and those who had conventional LASIK surgery [(15.99 +/- 7.14)/mm2, (19.39 +/- 7.07)/mm2, (11.30 +/- 3.17) mm/mm2, (68.43 +/- 34.94)/mm2, (4.73 +/- 0.24) microm, (2.14 +/- 0.34) grades] (t = -0.229, 0.049, 0.365, 0.306, -0.394, 1.629, P > 0.05). CONCLUSION: The difference between conventionalLASIK and femtosecond-assisted LASIK does not significantly affect the dry eye test values and nerve fiber measurements in patients at 1 year after LASIK. PMID- 26268642 TI - [Wavefront analysis and comparison between small incision lenticule extraction and femtosecond laser in situ keratomilensis]. AB - OBJECTIVE: To investigate and analyze the characteristic changes of high order aberrations before and after small incision lenticule extraction (SMILE) and femtosecond laser in situ keratomileusis (FS-LASIK). METHODS: Prospective study. Thirty-four patients (16 men and 18 women) underwent SMILE, and 28 cases (15 men and 13 women) underwent FS-LASIK, aged 18 to 39 years. Only the right eye was selected to be analyzed from each patient. All patients had conventional and Pentacam examinations preoperatively, and the ocular higher order aberrations were measured with the Hartman-Shack wavefront analyzer before surgery and at 1 month and 3 months postoperatively. The paired t test, independent t test, and Pearson correlation analysis were used to analyze the collected data. RESULTS: At the 1 month after SMILE group, C3(-1), C3(3) (-0.205 +/- 0.199, 0.027 +/- 0.071) were higher than the FS-LASIK group (0.004 +/- 0.316, -0.022 +/- 0.104) (t = 3.141, 2.216, P < 0.05), for FS-LASIK group Sh, S4 S5, S6, C4(0) (0.609 +/- 0.199, 0.403 +/- 0.196, 0.117 +/- 0.065, 0.092 +/- 0.038, 0.343 +/- 0.253) were higher than the SMILE group (0.461 +/- 0.130, 0.271 +/- 0.096, 0.074 +/- 0.028, 0.053 +/- 0.018, 0.239 +/- 0.121) (t = - 3.492, -3.461, -3.449, -5.301, -2.103, P < 0.05); At the 3rd month of SMILE group, C3(-1) (-0.177 +/- 0.175) was higher than the FS-LASIK group (-0.012 +/- 0.337) (t = -2.476, P < 0.05), In FS- LASIK group , however, the data for Sh, S4, S5, S6, C4(0) (0.626 +/- 0.215, 0.421 +/- 0.200, 0.108 +/- 0.066, 0.082 +/- 0.036, 0.393 +/- 0.207) were higher than the SMILE group (0.457 +/- 0.113, 0.270 +/- 0.106,0. 082 +/- 0.031, 0.051 +/- 0.017, 0.243 +/- 0.115 ) (t = -3.935, -3.788, -2.049, -4.405, -3.576, P < 0.05). With the correlation analysis, at the postoperative 1st and 3rd month of FS-LASIK group, Sh, C4(0) had negative relationship with the attempted myopic corrections (1 month post-op: r = - 0.433, -0.476, P < 0.05; 3 month post-op:r = -0.418, 0.447, P < 0.05). CONCLUSION: SMILE resulted in good optical quality early after operation. Compared with FS-LASIK, SMILE caused smaller change of ocular higher order aberrations, and each of them had its own particularity. Maybe it was associated with the surgery procedure and corneal wound healing after surgery. PMID- 26268643 TI - [The clinical features of 10 cases of acute retinal necrosis complicated by viral encephalitis]. AB - OBJECTIVE: To investigate the clinical features of acute retinal necrosis (ARN) complicated by viral encephalitis. METHODS: Ten cases of ARN complicated by viral encephalitis were treated in the Department of Ophthalmology, Beijing Tongren Hospital from November 2013 to August 2014. Clinical manifestation, especially the fundus characteristics, was summarized. RESULTS: In the10 patients (19 eyes; 6 men and 4 women) with an age of (40.1 +/- 13.44) years, 1 patients had unilateral ARN, and 9 patients had bilateral ARN. The visual acuity was no light perception in 9 eyes, light perception to hand motion in 7 eyes, 0.05 in 1 eye, 0.2 in 1 eye, and 0.3 in 1 eye. Seven cases suffered ARN during the onset of viral encephalitis, and other cases suffered ARN at 2 to 3 months after the recovery of viral encephalitis. Seventeen eyes had mild to moderate vitreous opacity, and 2 eye shad severe vitreous opacity. Sixteen eyes had focal (1 or 2 quadrants) retinal necrosis, and 2 eyes had massive ( > 2 quadrants) retinal necrosis. Occlusive vasculitis obviously occurred in 18 eyes. Sixteen eyeshad retinal detachment. All affected eyes had early optic nerve atrophy. CONCLUSION: ARN can occur during the onset of viral encephalitis or after the recovery of viral encephalitis. The clinical features of ARN complicated by viral encephalitis may be generally mild to moderate vitreous opacity,small range retinal necrosis foci, early and severe optic atrophy, and occlusive retinal vasculitis. PMID- 26268644 TI - [Effects of posterior chamber phakic intraocular lens on axial length measurements]. AB - OBJECTIVE: To study the effects of posterior chamber phakic intraocular lens (IOL) on axial length (AL) measurements and whether a correction factor for later IOL power calculation before cataract surgery is necessary. METHODS: Twenty-two high myopic patients (39 eyes) with mean spherical equivalent -19.00 +/- 4.03 D received phakic refractive lens (PRL) implantation, and 24 patients (40 eyes) with mean spherical equivalent (-13.10 +/- 2.53) D received implantable Collamer lens (ICL) implantation. Pre-and postoperative AL measurements with the IOLMaster were compared. Results The pre-and postoperative ALs were (30.87 +/- 2.18) mm and (30.94 +/- 2.16) mm, respectively (t = -2.635, P = 0.012) in the PRL group, and (28.35 +/- 1.20) mm and (28.45 +/- 1.22) mm, respectively ( t = -3.97, P < 0.001) in the ICL group. Linear regression analysis showed: in the PRL group, preoperative AL = 1.01 x postoperative AL-0.24 (R2 = 0.99, P < 0.001), or postoperative AL--preoperative AL = 0.24-0.0055 x postoperative AL; in the ICL group, preoperative AL = 0.96 x postoperative AL +1.17 (R2 = 0.99, P < 0.001), or postoperative AL--preoperative AL = 0.0154 x postoperative AL -0.3763. The mean differences between pre-and postoperative ALs in the PRL and, ICL groups were 0.075 mm and 0.054 mm, respectively. CONCLUSIONS: Based on the SRK formula, a < 0.1 mm AL difference would result in a <0.25 D change in the calculated IOL power, possibly a < 0.20 D change in manifest refraction. Furthermore, for PRL, the longer the AL, the smaller the difference between pre-and postoperative ALs. These differences are so small that it is unnecessary to correct IOL power calculation. PMID- 26268645 TI - [Statistical model analysis of primary angle closure glaucoma associated genes and SNP]. AB - OBJECTIVE: To evaluate GWAS significant associated SNP for primary angle closure glaucoma. METHODS: Experimental study. Taking advantage of different statistical models, the usefulness was evaluated by sensitivity, specificity and the area under the receiver-operating characteristic curve (ROC), which indicates the accuracy of genetic profiling in discriminating between primary angle closure glaucoma patients and normal controls. RESULTS: rs11024102 (PLEKHA7) had a sensitivity of 55.88% with a specificity of 51.31%; the sensitivity and specificity of rs3753841 (COL11A1) was 54.47% and 51.00% respectively. The sensitivity of rs1015213 (PCNTD1-ST18) and rs1401999 (ABCC5) were 59.93% and 52.97%. The specificity of these two SNP were 45.32% and 50.00%. The positive predictive value curves of these four SNP were nearly reference line. The area under the curve (AUC) of four SNP combined was 0.51 and 0.52 in two situations. CONCLUSION: These four GWAS significant SNP could not be used for primary angle closure glaucoma patients screening in clinic. PMID- 26268646 TI - [Changes in human meibum with meibomian gland dysfunction]. AB - Meibomian gland dysfunction (MGD) is a common ocular surface disease, characterized by terminal duct obstruction and (or) qualitative and quantitative changes in the glandular secretion. Meibomian lipids are a mixture consisting of various lipids, and they form the lipid layer of tear film and play important roles in preventing the evaporation and maintaining the stability of tear film. Patients with MGD may have different compositions of meibomian lipids, which could be an important indicator for diagnosis of MGD. The methods to analyze the composition of meibomian lipids mainly include chromatography and spectrum analysis. Because the pathogenic factors of MGD are still unclear, the main treatment is to relieve the symptoms. It can contribute to diagnose and treat MGD if we can find some convenient and effective methods to analyze the quality and quantity of meibomian lipids. PMID- 26268647 TI - [Expression and function of microRNAs in the cornea]. AB - MicroRNAs (miRNAs) are a class of small (21-2i nucleotictes), single-stranded, noncoding RNA molecules that regulate gene expression at the post-transcriptional or translational level by binding to the 3'-untranslated region of the target mRNAs. miRNAs ubiquitously exist in the genome of an organism. More than two hundred miRNA species are expressed in the eye, of which 25% are found in the cornea. miRNAs play important roles in corneal development, differentiation, glycogen metabolism, post-injury regeneration, and maintenance of homeostasis. On the other hand, miRNAs are involved in the regulation of pathological processes in the cornea, such as keratoconus, corneal neovascularization caused by corneal transplantation, herpes simplex virus infection and alkali burns. Therefore, miRNAs are expressed in a tissue-specific manner and regulate physiological and pathological processes in the cornea. The study of miRNA expression and regulation in the cornea would provide a theoretical basis for exploring pathogenic mechanisms and novel therapeutic targets for corneal diseases. PMID- 26268648 TI - [Progression of treatment and researches in dry age related macular degeneration]. AB - Age related macular degeneration (AMD) is the leading cause of blindness and visual disability among old patients in Europe and North America. AMD has been divided into two broad clinical categories depending on whether there is a presence of abnormal neovascularization: neovascular (exudative or wet) AMD and dry (or geographic atrophic) AMD. VEGF has been understood as a pathogenesis of wet AMD which allows us to get breakthroughs in treatment. While the progression of dry AMD treatment is very slow because the lack of pathogenesis, no acute loss of vision, and without appropriate standards for treatment. This review tries to introduce about the recent researches and progressions for dry AMD treatment. PMID- 26268649 TI - Selective Activation of C=C Bond in Sustainable Phenolic Compounds from Lignin via Photooxidation: Experiment and Density Functional Theory Calculations. AB - Lignocellulosic biomass can be converted to high-value phenolic compounds, such as food additives, antioxidants, fragrances and fine chemicals. We investigated photochemical and heterogeneous photocatalytic oxidation of two isomeric phenolic compounds from lignin, isoeugenol and eugenol, in several nonprotic solvents, for the first time by experiment and the density functional theory (DFT) calculations. Photooxidation was conducted under ambient conditions using air, near-UV light and commercial P25 TiO2 photocatalyst, and the products were determined by TLC, UV-Vis absorption spectroscopy, HPLC-UV and HPLC-MS. Photochemical and photocatalytic oxidation of isoeugenol proceeds via the mild oxidative "dimerization" to produce the lignan dehydrodiisoeugenol (DHDIE), while photooxidation of eugenol does not proceed. The DFT calculations suggest a radical stepwise mechanism for the oxidative "dimerization" of isoeugenol to DHDIE as was calculated for the first time. PMID- 26268650 TI - Preparation of core-shell structure Fe3 O4 @SiO2 superparamagnetic microspheres immoblized with iminodiacetic acid as immobilized metal ion affinity adsorbents for His-tag protein purification. AB - The core-shell structure Fe3 O4 /SiO2 magnetic microspheres were prepared by a sol-gel method, and immobiled with iminodiacetic acid (IDA) as metal ion affinity ligands for protein adsorption. The size, morphology, magnetic properties and surface modification of magnetic silica nanospheres were characterized by various modern analytical instruments. It was shown that the magnetic silica nanospheres exhibited superparamagnetism with saturation magnetization values of up to 58.1 emu/g. Three divalent metal ions, Cu(2+) , Ni(2+) and Zn(2+) , were chelated on the Fe3 O4 @SiO2 -IDA magnetic microspheres to adsorb lysozyme. The results indicated that Ni(2+) -chelating magnetic microspheres had the maximum adsorption capacity for lysozyme of 51.0 mg/g, adsorption equilibrium could be achieved within 60 min and the adsorbed protein could be easily eluted. Furthermore, the synthesized Fe3 O4 @SiO2 -IDA-Ni(2+) magnetic microspheres were successfully applied for selective enrichment lysozyme from egg white and His-tag recombinant Homer 1a from the inclusion extraction expressed in Escherichia coli. The result indicated that the magnetic microspheres showed unique characteristics of high selective separation behavior of protein mixture, low nonspecific adsorption, and easy handling. This demonstrates that the magnetic silica microspheres can be used efficiently in protein separation or purification and show great potential in the pretreatment of the biological sample. PMID- 26268652 TI - Role of B Cells in Mucosal Vaccine-Induced Protective CD8+ T Cell Immunity against Pulmonary Tuberculosis. AB - Emerging evidence suggests a role of B cells in host defense against primary pulmonary tuberculosis (TB). However, the role of B cells in TB vaccine-induced protective T cell immunity still remains unknown. Using a viral-vectored model TB vaccine and a number of experimental approaches, we have investigated the role of B cells in respiratory mucosal vaccine-induced T cell responses and protection against pulmonary TB. We found that respiratory mucosal vaccination activated Ag specific B cell responses. Whereas respiratory mucosal vaccination elicited Ag specific T cell responses in the airway and lung interstitium of genetic B cell deficient (Jh(-/-) knockout [KO]) mice, the levels of airway T cell responses were lower than in wild-type hosts, which were associated with suboptimal protection against pulmonary Mycobacterium tuberculosis challenge. However, mucosal vaccination induced T cell responses in the airway and lung interstitium and protection in B cell-depleted wild-type mice to a similar extent as in B cell competent hosts. Furthermore, by using an adoptive cell transfer approach, reconstitution of B cells in vaccinated Jh(-/-) KO mice did not enhance anti-TB protection. Moreover, respiratory mucosal vaccine-activated T cells alone were able to enhance anti-TB protection in SCID mice, and the transfer of vaccine primed B cells alongside T cells did not further enhance such protection. Alternatively, adoptively transferring vaccine-primed T cells from Jh(-/-) KO mice into SCID mice only provided suboptimal protection. These data together suggest that B cells play a minimal role, and highlight a central role by T cells, in respiratory mucosal vaccine-induced protective immunity against M. tuberculosis. PMID- 26268651 TI - Transcription Factor Repertoire of Homeostatic Eosinophilopoiesis. AB - The production of mature eosinophils (Eos) is a tightly orchestrated process with the aim to sustain normal Eos levels in tissues while also maintaining low numbers of these complex and sensitive cells in the blood. To identify regulators of homeostatic eosinophilopoiesis in mice, we took a global approach to identify genome-wide transcriptome and epigenome changes that occur during homeostasis at critical developmental stages, including Eos-lineage commitment and lineage maturation. Our analyses revealed a markedly greater number of transcriptome alterations associated with Eos maturation (1199 genes) than with Eos-lineage commitment (490 genes), highlighting the greater transcriptional investment necessary for differentiation. Eos-lineage-committed progenitors (EoPs) were noted to express high levels of granule proteins and contain granules with an ultrastructure distinct from that of mature resting Eos. Our analyses also delineated a 976-gene Eos-lineage transcriptome that included a repertoire of 56 transcription factors, many of which have never previously been associated with Eos. EoPs and Eos, but not granulocyte-monocyte progenitors or neutrophils, expressed Helios and Aiolos, members of the Ikaros family of transcription factors, which regulate gene expression via modulation of chromatin structure and DNA accessibility. Epigenetic studies revealed a distinct distribution of active chromatin marks between genes induced with lineage commitment and genes induced with cell maturation during Eos development. In addition, Aiolos and Helios binding sites were significantly enriched in genes expressed by EoPs and Eos with active chromatin, highlighting a potential novel role for Helios and Aiolos in regulating gene expression during Eos development. PMID- 26268653 TI - B Cell-Specific MHC Class II Deletion Reveals Multiple Nonredundant Roles for B Cell Antigen Presentation in Murine Lupus. AB - B cells have both Ab-dependent and Ab-independent functions in systemic autoimmune diseases, including systemic lupus erythematosus (SLE). Ab-independent functions are known to be important, because mice with B cells but no secreted Ig have severe disease. These functions could include roles in lymphoid development, cytokine secretion, and Ag presentation; however, these possibilities have not been directly tested in SLE models. In this study, we show by lineage-specific ablation of MHC class II (MHCII) that B cell Ag presentation plays a nonredundant role in CD4(+) T cell activation and effector differentiation in the MRL.Fas(lpr) mouse model of SLE. MHCII-mediated interactions between B and T cells further promote B cell proliferation and differentiation, and, in fact, inefficient MHCII deletion on B cells led to strong selection of escaped cells in activated and plasmablast compartments, further underscoring the central role of B cell Ag presentation. Despite the leakiness in the system, B cell-specific MHCII deletion resulted in substantially ameliorated clinical disease. Hence, B cell Ag presentation is critical for T and B cell activation and differentiation, as well as target organ damage. PMID- 26268654 TI - Inhibition of B Lymphopoiesis by Adipocytes and IL-1-Producing Myeloid-Derived Suppressor Cells. AB - B lymphopoiesis declines with age, and this decline correlates with increased adipose tissue in the bone marrow (BM). Also, adipocyte-derived factors are known to inhibit B lymphopoiesis. Using cocultures of mouse BM cells with OP9 stromal cells, we found that adipocyte-conditioned medium induces the generation of CD11b(+)Gr1(+) myeloid cells, which inhibit B cell development in vitro. Adipocyte-conditioned medium-induced CD11b(+)Gr1(+) cells express Arg1 (arginase) and Nos2 (inducible NO synthase) and suppress CD4(+) T cell proliferation, indicating that these cells are myeloid-derived suppressor cells (MDSCs). Blocking arginase and inducible NO synthase did not restore B lymphopoiesis, indicating that inhibition is not mediated by these molecules. Transwell and conditioned-medium experiments showed that MDSCs inhibit B lymphopoiesis via soluble factors, and by cytokine array we identified IL-1 as an important factor. Addition of anti-IL-1 Abs restored B lymphopoiesis in BM cultures containing MDSCs, showing that MDSC inhibition of B lymphopoiesis is mediated by IL-1. By treating hematopoietic precursors with IL-1, we found that multipotent progenitors are targets of IL-1. This study uncovers a novel function for MDSCs to inhibit B lymphopoiesis through IL-1. We suggest that inflammaging contributes to a decline of B lymphopoiesis in aged individuals, and furthermore, that MDSCs and IL-1 provide therapeutic targets for restoration of B lymphopoiesis in aged and obese individuals. PMID- 26268656 TI - Multiple Hepcidins in a Teleost Fish, Dicentrarchus labrax: Different Hepcidins for Different Roles. AB - Teleost fish rely heavily on their innate immunity for an adequate response against pathogens and environmental challenges, with the production of antimicrobial peptides being one of their first lines of defense. Among those is hepcidin, a small cysteine-rich antimicrobial peptide that is also the key regulator of iron metabolism. Although most mammals possess a single hepcidin gene, with a dual role in both iron metabolism regulation and antimicrobial response, many teleost fish present multiple copies of hepcidin, most likely because of genome duplications and positive Darwinian selection, suggesting that different hepcidins may perform different functions. To study the roles of hepcidin in teleost fish, we have isolated and characterized several genes in the European sea bass (Dicentrarchus labrax) and evaluated variations in their expression levels in response to different experimental conditions. Although several hepcidin genes were found, after phylogenetic analysis they could be clustered in two groups: hamp1-like, with a single isoform similar to mammalian hepcidins, and hamp2-like, with several isoforms. Under experimental conditions, hamp1 was upregulated in response to iron overload and infection and downregulated during anemia and hypoxic conditions. Hamp2 did not respond to either iron overload or anemia but was highly upregulated during infection and hypoxia. In addition, Hamp2 synthetic peptides exhibited a clear antimicrobial activity against several bacterial strains in vitro. In conclusion, teleost fish that present two hepcidin types show a degree of subfunctionalization of its functions, with hamp1 more involved in the regulation of iron metabolism and hamp2 mostly performing an antimicrobial role. PMID- 26268655 TI - Transmembrane TNF-TNFR2 Impairs Th17 Differentiation by Promoting Il2 Expression. AB - The double-edged sword nature by which IL-2 regulates autoimmunity and the unpredictable outcomes of anti-TNF therapy in autoimmunity highlight the importance for understanding how TNF regulates IL-2. Transmembrane TNF (tmTNF) preferentially binds TNFR2, whereas soluble TNF (sTNF) binds TNFR1. We previously showed reduced IL-2 production in TNFR1(-/-) TNFR2(-/-) CD4(+) T cells. In this study, we generated TNFR1(-/-), TNFR2(-/-), or TNFR1(-/-) TNFR2(-/-) 5C.C7 TCR Il2-GFP mice and report that CD4(+) T cell-intrinsic tmTNF/TNFR2 stimulates Il2 promoter activity and Il2 mRNA stability. We further used tmTNF Foxp3 gfp reporter mice and pharmacological TNF blockade in wild-type mice to report a tmTNF/TNFR2 interaction for Il2 expression. IL-17 is critical for host defense, but its overabundance promotes autoimmunity. IL-2 represses Th17 differentiation, but the role for TNFR2 in this process is not well understood. We report elevated expression of TNFR2 under Th17-polarization conditions. Genetic loss-of-function experimental models, as well as selective TNF blockade by etanercept and XPro1595 in wild-type mice, demonstrate that impaired tmTNF/TNFR2, but not sTNF/TNFR1, promotes Th17 differentiation in vivo and in vitro. Under Th17-polarizing conditions, elevated IL-17 production by TNFR2-knockout CD4(+) T cells was associated with increased STAT3 activity and decreased STAT5 activity. Increased IL-17 production in TNFR2-knockout T cells was prevented by adding exogenous IL 2. We conclude that CD4(+) T cell-intrinsic tmTNF/TNFR2 promotes IL-2 production that inhibits the generation of Th17 cells in a Foxp3-independent manner. Moreover, under Th17-polarizing conditions, selective blockade of CD4(+) T cell intrinsic TNFR2 appears to be sufficient to promote Th17 differentiation. PMID- 26268657 TI - MicroRNA-15/16 Antagonizes Myb To Control NK Cell Maturation. AB - NK cells develop in the bone marrow and complete their maturation in peripheral organs, but the molecular events controlling maturation are incompletely understood. The miR-15/16 family of microRNA regulates key cellular processes and is abundantly expressed in NK cells. In this study, we identify a critical role for miR-15/16 in the normal maturation of NK cells using a mouse model of NK specific deletion, in which immature NK cells accumulate in the absence of miR 15/16. The transcription factor c-Myb (Myb) is expressed preferentially by immature NK cells, is a direct target of miR-15/16, and is increased in 15a/16-1 floxed knockout NK cells. Importantly, maturation of 15a/16-1 floxed knockout NK cells was rescued by Myb knockdown. Moreover, Myb overexpression in wild-type NK cells caused a defective NK cell maturation phenotype similar to deletion of miR 15/16, and Myb overexpression enforces an immature NK cell transcriptional profile. Thus, miR-15/16 regulation of Myb controls the NK cell maturation program. PMID- 26268658 TI - Heme Oxygenase-1 Regulation of Matrix Metalloproteinase-1 Expression Underlies Distinct Disease Profiles in Tuberculosis. AB - Pulmonary tuberculosis (TB) is characterized by oxidative stress and lung tissue destruction by matrix metalloproteinases (MMPs). The interplay between these distinct pathological processes and the implications for TB diagnosis and disease staging are poorly understood. Heme oxygenase-1 (HO-1) levels were previously shown to distinguish active from latent TB, as well as successfully treated Mycobacterium tuberculosis infection. MMP-1 expression is also associated with active TB. In this study, we measured plasma levels of these two important biomarkers in distinct TB cohorts from India and Brazil. Patients with active TB expressed either very high levels of HO-1 and low levels of MMP-1 or the converse. Moreover, TB patients with either high HO-1 or MMP-1 levels displayed distinct clinical presentations, as well as plasma inflammatory marker profiles. In contrast, in an exploratory North American study, inversely correlated expression of HO-1 and MMP-1 was not observed in patients with other nontuberculous lung diseases. To assess possible regulatory interactions in the biosynthesis of these two enzymes at the cellular level, we studied the expression of HO-1 and MMP-1 in M. tuberculosis-infected human and murine macrophages. We found that infection of macrophages with live virulent M. tuberculosis is required for robust induction of high levels of HO-1 but not MMP 1. In addition, we observed that CO, a product of M. tuberculosis-induced HO-1 activity, inhibits MMP-1 expression by suppressing c-Jun/AP-1 activation. These findings reveal a mechanistic link between oxidative stress and tissue remodeling that may find applicability in the clinical staging of TB patients. PMID- 26268659 TI - CXCL9 Regulates TGF-beta1-Induced Epithelial to Mesenchymal Transition in Human Alveolar Epithelial Cells. AB - Epithelial to mesenchymal cell transition (EMT), whereby fully differentiated epithelial cells transition to a mesenchymal phenotype, has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). CXCR3 and its ligands are recognized to play a protective role in pulmonary fibrosis. In this study, we investigated the presence and extent of EMT and CXCR3 expression in human IPF surgical lung biopsies and assessed whether CXCR3 and its ligand CXCL9 modulate EMT in alveolar epithelial cells. Coexpression of the epithelial marker thyroid transcription factor-1 and the mesenchymal marker alpha-smooth muscle actin and CXCR3 expression was examined by immunohistochemical staining of IPF surgical lung biopsies. Epithelial and mesenchymal marker expression was examined by quantitative real-time PCR, Western blotting, and immunofluorescence in human alveolar epithelial (A549) cells treated with TGF-beta1 and CXCL9, with Smad2, Smad3, and Smad7 expression and cellular localization examined by Western blotting. We found that significantly more cells were undergoing EMT in fibrotic versus normal areas of lung in IPF surgical lung biopsy samples. CXCR3 was expressed by type II pneumocytes and fibroblasts in fibrotic areas in close proximity to cells undergoing EMT. In vitro, CXCL9 abrogated TGF-beta1-induced EMT. A decrease in TGF-beta1-induced phosphorylation of Smad2 and Smad3 occurred with CXCL9 treatment. This was associated with increased shuttling of Smad7 from the nucleus to the cytoplasm where it inhibits Smad phosphorylation. This suggests a role for EMT in the pathogenesis of IPF and provides a novel mechanism for the inhibitory effects of CXCL9 on TGF-beta1-induced EMT. PMID- 26268660 TI - Use of anti-dementia drugs in home care and residential care and associations with neuropsychiatric symptoms: a cross-sectional study. AB - BACKGROUND: The number of people with dementia is increasing alongside the aging population, and most of these patients manifest with neuropsychiatric symptoms (NPS). The objective of this study was to investigate anti-dementia drug use and its associations with NPS. METHODS: Questionnaires on demographic information, current drug use, activities of daily living and NPS were sent to all municipal home care producers and to all institutions providing long-term residential care in the South Savo Hospital District, Finland. RESULTS: The study population comprised 2821 persons. Their mean age was 81 years and 68% were female. Dementia had been diagnosed in 31% (n = 410) in home care and in 56% (n = 774) in residential care. Anti-dementia drugs were used by 69% of patients with dementia. Hyperactivity symptoms were common in residential care patients (n = 456, 33%), while problems with mood and apathy dominated in home care patients (n = 486, 54%). In multivariate regression analysis, the mood symptoms and apathy subgroup was associated with use of an acetylcholinesterase inhibitor (AChEI) (OR 1.44; 95% Cl 1.03-2.02), memantine (OR 1.77, 95% Cl 1.15-2.72) or their combinations (OR 1.56, 95% Cl 1.03-2.34). Hyperactivity symptoms were associated with combination therapy of this type (OR 2.03, 95% Cl 1.36-2.34). CONCLUSIONS: The use of anti-dementia drugs was common in both care settings. The use of any anti dementia drug or combination was associated with the mood and apathy subgroup. The hyperactivity subgroup was associated with combination use of memantine and AChEI. PMID- 26268661 TI - Growth hormone modulates hypothalamic inflammation in long-lived pituitary dwarf mice. AB - Mice in which the genes for growth hormone (GH) or GH receptor (GHR(-/-) ) are disrupted from conception are dwarfs, possess low levels of IGF-1 and insulin, have low rates of cancer and diabetes, and are extremely long-lived. Median longevity is also increased in mice with deletion of hypothalamic GH-releasing hormone (GHRH), which leads to isolated GH deficiency. The remarkable extension of longevity in hypopituitary Ames dwarf mice can be reversed by a 6-week course of GH injections started at the age of 2 weeks. Here, we demonstrate that mutations that interfere with GH production or response, in the Snell dwarf, Ames dwarf, or GHR(-/-) mice lead to reduced formation of both orexigenic agouti related peptide (AgRP) and anorexigenic proopiomelanocortin (POMC) projections to the main hypothalamic projection areas: the arcuate nucleus (ARH), paraventricular nucleus (PVH), and dorsomedial nucleus (DMH). These mutations also reduce hypothalamic inflammation in 18-month-old mice. GH injections, between 2 and 8 weeks of age, reversed both effects in Ames dwarf mice. Disruption of GHR specifically in liver (LiGHRKO), a mutation that reduces circulating IGF-1 but does not lead to lifespan extension, had no effect on hypothalamic projections or inflammation, suggesting an effect of GH, rather than peripheral IGF-1, on hypothalamic development. Hypothalamic leptin signaling, as monitored by induction of pStat3, is not impaired by GHR deficiency. Together, these results suggest that early-life disruption of GH signaling produces long term hypothalamic changes that may contribute to the longevity of GH-deficient and GH-resistant mice. PMID- 26268662 TI - A multi-subunit Chlamydia vaccine inducing neutralizing antibodies and strong IFN gamma+ CMI responses protects against a genital infection in minipigs. AB - Chlamydia is the most widespread sexually transmitted bacterial disease and a prophylactic vaccine is highly needed. Ideally, this vaccine is required to induce a combined response of Th1 cell-mediated immune (CMI) response in concert with neutralizing antibodies. Using a novel Gottingen minipig animal model, we evaluated the immunogenicity and efficacy of a multi-subunit vaccine formulated in the strong Th1-inducing adjuvant CAF01. We evaluated a mixture of two fusion proteins (Hirep1 and CTH93) designed to promote either neutralizing antibodies or cell-mediated immunity, respectively. Hirep1 is a novel immunogen based on the variant domain (VD) 4 region from major outer membrane protein (MOMP) serovar (Sv) D, SvE and SvF, and CTH93 is a fusion molecule of three antigens (CT043, CT414 and MOMP). Pigs were immunized twice intramuscularly with either Hirep1+CTH93/CAF01, UV-inactivated Chlamydia trachomatis SvD bacteria (UV SvD/CAF01) or CAF01. The Hirep1+CTH93/CAF01 vaccine induced a strong CMI response against the vaccine antigens and high titers of antibodies, particularly against the VD4 region of MOMP. Sera from Hirep1+CTH93/CAF01 immunized pigs neutralized C. trachomatis SvD and SvF infectivity in vitro. Both Hirep1+CTH93/CAF01 and UV SvD/CAF01 vaccination protected pigs against a vaginal C. trachomatis SvD infection. In conclusion, the Hirep1+CTH93/CAF01 vaccine proved highly immunogenic and equally protective as UV-SvD/CAF01 showing promise for the development of a subunit vaccine against Chlamydia. PMID- 26268664 TI - Localization of connexin 32 in spontaneous liver lesions of mice. AB - We examined the localization of connexin 32 (Cx32), a component of gap junctions, in 24-month-old male B6C3F1 mice with spontaneously occurring hepatocellular altered foci or tumors. Immunohistochemically, Cx32-staining intensity in cell-to cell membranes of altered hepatocytes was decreased in eosinophilic foci and increased in basophilic foci as compared to those in intact hepatocytes. These alterations were enhanced in adenomas and carcinomas with both eosinophilic and basophilic cytoplasm. In cell membranes facing on the sinusoidal portions, the intensities increased in all lesions. Image analyses confirmed that the spot areas of Cx32 were decreased in eosinophilic foci, but increased in basophilic foci, adenomas and carcinomas. These results demonstrate that Cx32 shows different expression in different types of hepatic lesions. PMID- 26268665 TI - Rapid detection of feline morbillivirus by a reverse transcription loop-mediated isothermal amplification. AB - Feline morbillivirus (FmoPV) is an emerging virus in domestic cats and considered to be one of the causes of chronic renal failure in cats. In this study, we established a reverse transcription loop-mediated isothermal amplification (RT LAMP) assay for the detection of FmoPV. The results indicated that the detection limit of the assay was 10 50% tissue culture infective dose (TCID50)/ml in the original sample, and sensitivity of the assay was calculated as 0.12 TCID50 per one RT-LAMP reaction. We also detected FmoPV in clinical urine samples from cats infected with FmoPV. The FmoPV RT-LAMP assay is rapid, simple and highly specific for the detection of FmoPV, and thus, it would be a reliable detection method for FmoPV. PMID- 26268666 TI - Identification of a novel miRNA from the ovine ovary by a combinatorial approach of bioinformatics and experiments. AB - MicroRNAs (miRNAs) are a class of short endogenous, single-stranded, non-coding small RNA molecules, about 19-25 nucleotides in length that regulate gene expression at the translation level and influence many physiological process, such apoptosis, metabolism, signal transduction, and occurrence and development of diseases. In this study, we constructed a library from the ovine luteal phase ovary by using next-generation sequencing technology (Solexa high-throughput sequencing technique) and identified 267 novel miRNAs by bioinformatics. One of the novel miRNAs (ovis_aries_ovary-m0033_3p), which expressed in the sheep ovary and testis, was confirmed by real time PCR and northern blot. Ovis_aries_ovary m0033_3p was 21 nucleotides in length and located on chromosome 12, and it had 100% similarity to hsa-miR-214-3p, mmu-miR-214-3p, dre-miR-214and ssc-miR-214. Meanwhile, the pre-miRNA was 82 nucleotides in length and had a standard hairpin stem-loop structure. From the consistency of the sequence and structure, we speculated that ovis_aries_ovary-m0033_3p had a function similar to hsa-miR-214 3p, which is involved in the fine regulation of cell survival, embryonic development, breeding activities and resistance to ovarian cancer, so we defined it as oar-miR-214-3p. These experimental results will enrich the miRNA database for ovis aries and provide the basis for researching the regulation mechanism of miRNA in relation to breeding activities of seasonal breeding animals. PMID- 26268663 TI - Baseline genetic associations in the Parkinson's Progression Markers Initiative (PPMI). AB - BACKGROUND: The Parkinson's Progression Marker Initiative is an international multicenter study whose main goal is investigating markers for Parkinson's disease (PD) progression as part of a path to a treatment for the disease. This manuscript describes the baseline genetic architecture of this study, providing not only a catalog of disease-linked variants and mutations, but also quantitative measures with which to adjust for population structure. METHODS: Three hundred eighty-three newly diagnosed typical PD cases, 65 atypical PD and 178 healthy controls, from the Parkinson's Progression Marker Initiative study have been genotyped on the NeuroX or Immunochip arrays. These data are freely available to all researchers interested in pursuing PD research within the Parkinson's Progression Marker Initiative. RESULTS: The Parkinson's Progression Marker Initiative represents a study population with low genetic heterogeneity. We recapitulate known PD associations from large-scale genome-wide association studies and refine genetic risk score models for PD predictability (area under the curve, ~0.74). We show the presence of six LRRK2 p.G2019S and nine GBA p.N370S mutation carriers. CONCLUSIONS: The Parkinson's Progression Marker Initiative study and its genetic data are useful in studies of PD biomarkers. The genetic architecture described here will be useful in the analysis of myriad biological and clinical traits within this study. PMID- 26268667 TI - From lithotroph- to organotroph-dominant: directional shift of microbial community in sulphidic tailings during phytostabilization. AB - Engineering microbial diversity to enhance soil functions may improve the success of direct revegetation in sulphidic mine tailings. Therefore, it is essential to explore how remediation and initial plant establishment can alter microbial communities, and, which edaphic factors control these changes under field conditions. A long-term revegetation trial was established at a Pb-Zn-Cu tailings impoundment in northwest Queensland. The control and amended and/or revegetated treatments were sampled from the 3-year-old trial. In total, 24 samples were examined using pyrosequencing of 16S rRNA genes and various chemical properties. The results showed that the microbial diversity was positively controlled by soil soluble Si and negatively controlled by soluble S, total Fe and total As, implying that pyrite weathering posed a substantial stress on microbial development in the tailings. All treatments were dominated by typical extremophiles and lithotrophs, typically Truepera, Thiobacillus, Rubrobacter; significant increases in microbial diversity, biomass and frequency of organotrophic genera (typically Nocardioides and Altererythrobacter) were detected in the revegetated and amended treatment. We concluded that appropriate phytostabilization options have the potential to drive the microbial diversity and community structure in the tailings toward those of natural soils, however, inherent environmental stressors may limit such changes. PMID- 26268668 TI - Exploring gender norms, agency and intimate partner violence among displaced Colombian women: A qualitative assessment. AB - Women displaced by conflict are often exposed to many factors associated with a risk of intimate partner violence (IPV) such as high levels of community violence and the breakdown of social support systems. Previous research found that Colombian women perceived IPV to increase after displacement. This study explored how the experience of displacement altered gendered roles in ways that influenced the risk of IPV. Thirty-three qualitative interviews were conducted with displaced partnered Colombian women. Women disclosed that couples often held patriarchal gender norms; however, the roles of each partner necessitated by conditions of displacement were often in conflict with these norms. Men's underemployment and women's employment outside the home were viewed as gender transgressive within some partnerships and increased relationship conflict. Economic resources intended to empower displaced women, notably women's earnings and home ownership, had unintended negative consequences for women's agency. These consequences included a corresponding decrease in partner financial contributions and reduced mobility. Women's ability to obtain support or leave violent relationships was hindered by interpersonal, social and structural barriers. For women to have agency to leave violent relationships, power relationships at all levels from the interpersonal to societal must be recognised and addressed. PMID- 26268669 TI - Influence of calcium chloride in the high temperature acetification by strain Acetobacter aceti WK for vinegar. AB - AIMS: To improve the thermotolerant properties (TTP) of acetic acid bacteria (AAB) cells for high temperature acetification. METHODS AND RESULTS: At high temperature (36 +/- 1 degrees C), the acetification rate (ETA) is usually lower than at 30 +/- 1 degrees C. The addition of 0.15% calcium chloride (CaCl2 ) may decrease the negative effect of the increase of temperature from 30 +/- 1 degrees C to 36 +/- 1 degrees C on the ETA. The effect of CaCl2 on the thermotolerant properties of acetic acid bacteria cells was investigated. The CaCl2 increased the content of phospholipids (phosphotidylcholine and phosphatidylglycerol), fatty acids (cis-vaccenic acid, palmitic acid and myristic acid) and the activities of membrane-bound enzymes involved in acetification, alcohol dehydrogenase and aldehyde dehydrogenase. Transmission electron microscope images revealed a more compact cell wall with CaCl2. Process consistency at 36 +/- 1 degrees C was tested in nine sequential acetification cycles using 0.15% (w/v) CaCl2. High ETAs (9.33 +/- 0.6; 8.67 +/- 0.8 and 9.67 +/- 0.7 g l(-1) day(-1)) were obtained during the last three cycles. CONCLUSIONS: The results confirm that changes of the content of lipid, activities of membrane-bound enzymes and cell wall thickness occurred with added CaCl2. SIGNIFICANCE AND IMPACT OF THE STUDY: High temperature acetification (HTA) with additions of CaCl2 was investigated. Significant reductions in the overall production costs result from lower cooling costs associated with HTA. PMID- 26268670 TI - Oral plexiform schwannoma with unusual epithelial induction. AB - Rare epithelial structures in benign nerve sheath tumors are almost always glandular in appearance. We describe a case of intraoral plexiform schwannoma with concurrent squamous epithelial hyperplasia. The lesion occurred as a pigmented nodule on the gingiva of a 35-year-old woman with no systemic involvement. Histologically, unencapsulated, plexiform fascicular proliferations of schwann cells could be traced from the submucosa to the lamina propria, finally making direct contact with heavily pigmented, elongated rete ridges of the overlying epithelium. Also noted was a schwannian network centered on clustered odontogenic epithelial rests of mature squamous-type, the number and size of which had markedly increased. Impressive immunoprofiles of periepithelial neural microfascicles included the complete absence of axon and perineurium and the unexpected presence of endoneurial fibroblasts. The repertoire of epithelial changes was in a confined area with no extension beyond, supporting hyperplasia induction by an underlying/surrounding schwannoma. PMID- 26268671 TI - Erratum to: Laparoscopic ventral/incisional hernia repair: updated Consensus Development Conference based guidelines. PMID- 26268673 TI - Is Transcranial Direct Current Stimulation an Effective Predictor for Invasive Occipital Nerve Stimulation Treatment Success in Fibromyalgia Patients? AB - BACKGROUND: Fibromyalgia is a disorder distinguished by pervasive musculoskeletal pain that has pervasive effects on affected individuals magnifying the importance of finding a safe and viable treatment option. OBJECTIVE: The goal of this study is to investigate if transcranial direct current stimulation (tDCS) treatment can predict the outcome of occipital nerve field stimulation (ONFS) via a subcutaneous electrode. METHODS: Nine patients with fibromyalgia were selected fulfilling the American College of Rheumatology-90 criteria. The patients were implanted with a subcutaneous trial-lead in the C2 dermatome innervated by the occipital nerve. After the treatment phase of ONFS using a C2 implant, each patient participated in three sessions of tDCS. Stimulation outcomes for pain suppression were examined between the two methods to determine possible correlations. RESULTS: Positive correlation of stimulation effect was noted between the numeric rating scale changes for pain obtained by tDCS treatments and short-term measures of ONFS, but no correlation was noted between tDCS and long term ONFS outcomes. A correlation also was noted between short-term ONS C2 implant pain suppression and long-term ONS C2 implant treatment success. CONCLUSIONS: This pilot study suggests that tDCS is a predictive measure for success of OFNS in short-term but cannot be used as a predictive measure for success of long-term OFNS. Our data confirm previous findings that ONFS via an implanted electrode can improve fibromyalgia pain in a placebo-controlled way and exert a long-term pain suppression effect for ONFS via an implanted electrode. PMID- 26268674 TI - Discriminative Chemical Patterns: Automatic and Interactive Design. AB - The classification of molecules with respect to their inhibiting, activating, or toxicological potential constitutes a central aspect in the field of cheminformatics. Often, a discriminative feature is needed to distinguish two different molecule sets. Besides physicochemical properties, substructures and chemical patterns belong to the descriptors most frequently applied for this purpose. As a commonly used example of this descriptor class, SMARTS strings represent a powerful concept for the representation and processing of abstract chemical patterns. While their usage facilitates a convenient way to apply previously derived classification rules on new molecule sets, the manual generation of useful SMARTS patterns remains a complex and time-consuming process. Here, we introduce SMARTSminer, a new algorithm for the automatic derivation of discriminative SMARTS patterns from preclassified molecule sets. Based on a specially adapted subgraph mining algorithm, SMARTSminer identifies structural features that are frequent in only one of the given molecule classes. In comparison to elemental substructures, it also supports the consideration of general and specific SMARTS features. Furthermore, SMARTSminer is integrated into an interactive pattern editor named SMARTSeditor. This allows for an intuitive visualization on the basis of the SMARTSviewer concept as well as interactive adaption and further improvement of the generated patterns. Additionally, a new molecular matching feature provides an immediate feedback on a pattern's matching behavior across the molecule sets. We demonstrate the utility of the SMARTSminer functionality and its integration into the SMARTSeditor software in several different classification scenarios. PMID- 26268675 TI - Tailoring the strength and porosity of rapid-hardening magnesia phosphate paste via the pre-foaming method. AB - High-porosity magnesia phosphate paste (HPMPP) was prepared via the pre-foaming method. In the pre-foaming method, sintering treatment was not required. The bulk density and maximum compressive strength of the HPMPP prepared according to the ratio of water to solids (W/So) of 0.32 reached 464.00 +/- 5.00 Kg/m(3) and 0.30 +/- 0.05 MPa, respectively. The compressive strength increased with the increases in the addition amounts of sodium silicate and polypropylene fibers. The bulk density of HPMPP increased with the increase in the addition of sodium silicate and decreased with the increase in the addition of polypropylene fibers. Besides, the porosity of the magnesia phosphate paste increased from 79.85% to 81.27% and from 80.31% to 83.75% after the addition of sodium silicate and polypropylene fibers respectively. The highest porosity (83.75%) of the prepared HPMPP was realized under the addition proportion (sodium silicate: polypropylene fibers: solids = 0.06:0.0025:1). The average pore size of the prepared HPMPP is about 180 MUm and the pore distribution range is relatively narrow. The hydration product (struvite) is combined with MgO particle one by one and then coated on the surface of bubbles. With the decrease of the water content, after breaking bubbles, the porous structure can be achieved. PMID- 26268676 TI - The immune adherence receptor CR1-like existed on porcine erythrocytes membrane. AB - In the present study, we obtain a mouse anti-porcine complement receptor type 1 (CR1)-like monoclonal antibody (McAb) and use this McAb to verify the existence of CR1-like protein on porcine erythrocytes. Our results confirm that CR1-like protein is localized on the surface of porcine erythrocytes. Mouse immunoglobulin G inhibited the binding of serum-opsonized green fluorescent protein-expressing Escherichia coli to porcine erythrocytes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis indicates that CR1-like McAb reacts with biochemically-purified porcine erythrocyte membrane fractions, with a clear band at 135 kDa to 140 kDa. We postulate that the 135 kDa to 140 kDa membrane protein is the equivalent of the porcine erythrocyte CR1-like protein. PMID- 26268678 TI - Erratum. PMID- 26268677 TI - Cardio-oncology: a new discipline in medicine to lead us into truly integrative care. PMID- 26268679 TI - Peptide receptor radionuclide therapy (PRRT): clinical significance of re treatment? PMID- 26268680 TI - Recurrent renal cell carcinoma: clinical and prognostic value of FDG PET/CT. AB - PURPOSE: The purpose of our study was 1) to evaluate the diagnostic performance of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT), 2) to assess the impact of FDG PET/CT on treatment decision making, and 3) to estimate the prognostic value of FDG PET/CT in the restaging process among patients with renal cell carcinoma (RCC). METHODS: From the FDG PET/CT databases of San Raffaele Hospital in Milan, Italy, and the Veneto Institute of Oncology in Padua, Italy, we selected 104 patients with a certain diagnosis of RCC after surgery, and for whom at least 24 months of post-surgical FDG PET/CT, clinical, and instrumental follow-up data was available. The sensitivity and specificity of FDG PET/CT were assessed by histology and/or other imaging as standard of reference. Progression-free survival (PFS) and overall survival (OS) were computed using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used to identify predictors of outcome. RESULTS: FDG PET/CT resulted in a positive diagnosis in 58 patients and a negative diagnosis in 46 patients. Sensitivity and specificity were 74% and 80%, respectively. FDG PET/CT findings influenced therapeutic management in 45/104 cases (43%). After a median follow-up period of 37 months (+/- standard deviation 12.9), 51 (49%) patients had recurrence of disease, and 26 (25%) had died. In analysis of OS, positive versus negative FDG PET/CT was associated with worse cumulative survival rates over a 5-year period (19% vs. 69%, respectively; p <0.05). Similarly, a positive FDG PET/CT correlated with a lower 3-year PFS rate. In addition, univariate and multivariate analysis revealed that a positive scan, alone or in combination with disease stage III-IV or nuclear grading 3-4, was associated with high risk of progression (multivariate analysis = hazard ratios [HRs] of 4.01, 3.7, and 2.8, respectively; all p < 0.05). CONCLUSIONS: FDG PET/CT is a valuable tool both in treatment decision-making and for predicting survival and progression in patients affected by RCC. PMID- 26268682 TI - An injectable hydrogel derived from small intestine submucosa as a stem cell carrier. AB - Small intestine submucosa (SIS) is used as an attractive biomaterial in the field of regenerative medicine because it possesses numerous bioactive factors such as cell adhesion proteins, growth factors, and glycosaminoglycans. In most cases, SIS has been used as sheet and sponge-like forms. The goal of present study was to prepare an injectable SIS hydrogel and to examine the feasibility as an in vivo stem cell carrier of injectable SIS hydrogel form. The rat muscle-derived stem cells (rMDSCs) were simply incorporated into SIS hydrogel by mixing. The SIS hydrogel showed a porous microstructure. In vitro cytotoxicity test, attachment, and proliferation of rMDSCs on the SIS hydrogel were higher than those on tissue culture dishes. Then rMDSCs-loaded SIS hydrogel was subcutaneously injected into rats. The in vivo formed rMDSCs-loaded SIS hydrogel implant induced the ingrowth of new vessels and cell proliferation. In addition, SIS and rMDSCs suppressed macrophage-mediated inflammation. In conclusion, we confirmed that injectable SIS hydrogel could serve as a minimally invasive stem cell carrier. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1544-1550, 2016. PMID- 26268683 TI - Structural defect induced peak splitting in gold-copper bimetallic nanorods during growth by single particle spectroscopy. AB - A single particle level study of bimetallic nanoparticle growth provides valuable information that is usually hidden in ensemble measurements, helping to improve the understanding of a reaction mechanism and overcome the synthetic challenges. In this study, we use single particle spectroscopy to monitor the changes in the scattering spectra of Au-Cu alloy nanorods during growth. We found that the unique features of the single particle scattering spectra were due to atomic level geometric defects in the nanorods. Electrodynamics simulations have demonstrated that small structural defects of a few atomic layers split the scattering peaks, giving rise to higher order modes, which do not exist in defect free rods of similar geometry. The study shows that single particle scattering technique is as sensitive as high-resolution electron microscopy in revealing atomic level structural defects. PMID- 26268681 TI - Comparative analyses of CTCF and BORIS occupancies uncover two distinct classes of CTCF binding genomic regions. AB - BACKGROUND: CTCF and BORIS (CTCFL), two paralogous mammalian proteins sharing nearly identical DNA binding domains, are thought to function in a mutually exclusive manner in DNA binding and transcriptional regulation. RESULTS: Here we show that these two proteins co-occupy a specific subset of regulatory elements consisting of clustered CTCF binding motifs (termed 2xCTSes). BORIS occupancy at 2xCTSes is largely invariant in BORIS-positive cancer cells, with the genomic pattern recapitulating the germline-specific BORIS binding to chromatin. In contrast to the single-motif CTCF target sites (1xCTSes), the 2xCTS elements are preferentially found at active promoters and enhancers, both in cancer and germ cells. 2xCTSes are also enriched in genomic regions that escape histone to protamine replacement in human and mouse sperm. Depletion of the BORIS gene leads to altered transcription of a large number of genes and the differentiation of K562 cells, while the ectopic expression of this CTCF paralog leads to specific changes in transcription in MCF7 cells. CONCLUSIONS: We discover two functionally and structurally different classes of CTCF binding regions, 2xCTSes and 1xCTSes, revealed by their predisposition to bind BORIS. We propose that 2xCTSes play key roles in the transcriptional program of cancer and germ cells. PMID- 26268684 TI - Sexual dysfunction in testicular cancer patients subjected to post-chemotherapy retroperitoneal lymph node dissection: a focus beyond ejaculation disorders. AB - Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) represents an integral part of multidisciplinary treatment of advanced germ cell cancer; however, it is associated with a high complications rate. The present study aimed to describe sexual disorders in 53 patients with testicular cancer who underwent full bilateral, non-nerve-sparing PC-RPLND in our institution, focusing beyond ejaculatory dysfunction. The International Index for Erectile Function (IIEF) questionnaire was used as diagnostic tool of male sexual functioning pre operatively and three months after RPLND, while post-operatively patients were asked to describe and evaluate changes in selected sexual parameters. Study findings demonstrate mixed pattern of changes in sexual functioning, with no difference in erectile functioning before and after operation. However, orgasmic function and intercourse and overall sexual satisfaction were found significantly impaired post-operatively. Sexual desire and frequency of attempted sexual intercourses were found significantly increased post-operatively, in comparison with pre-operative levels. With regard to patients' subjective perception on sexual functioning alterations after PC-RPLND, a significant number of patients reported higher levels of sexual desire, no difference in erectile function and worse orgasmic function and satisfaction post-operatively. Thus, patients subjected to PC-RPLND should be closely and routinely evaluated due to close relationship of sexual dissatisfaction with secondary psychological disorders. PMID- 26268686 TI - Correction to "Electromechanical Signatures for DNA Sequencing through a Mechanosensitive Nanopore". PMID- 26268688 TI - An opportunity for further control of hepatitis B in China? PMID- 26268687 TI - Seroepidemiology of hepatitis B virus infection in 2 million men aged 21-49 years in rural China: a population-based, cross-sectional study. AB - BACKGROUND: Hepatitis B virus (HBV) infection is highly endemic (7-8% prevalence) in rural China, causing high mortality and societal burden. Data from men of reproductive age is scarce and last reported in 2006. We assessed the seroepidemiology of men in rural China, aiming to provide updated baseline data for the prevalence of HBV infection. METHODS: We established prevalence of HBV infection from data gathered through a nationwide population-based study of Chinese rural men aged 21-49 years. Data were obtained from a physical check-up programme for couples of reproductive age, the National Free Preconception Health Examination Project, that covered 31 provinces from 2010-12. We tested serological samples with ELISA and categorised participants' HBV status based on presence of HBsAg, anti-HBV core antibody (anti-HBc), and anti-HBV surface antibody (anti-HBs). FINDINGS: 2 030 083 men were recruited into the database from Jan 1, 2010, to Dec 31, 2012, and 1 966 013 men provided serum samples for analysis. 124 274 men (6%) tested positive for HBsAg, 178 559 (9%) tested positive for anti-HBc, and 583 923 (30%) tested positive for anti-HBs. Isolated anti-HBs (an indicator of vaccine-mediated immunity) were present in 527 566 men (27%). And 1 234 127 men (63%) were negative for all HBV makers (susceptible population). HBsAg prevalence was higher in men aged 25-39 years (6.35-6.47%) than in other age groups (5.54-5.78%; p<0.0001). HBV markers were all more prevalent in the eastern region of China than in the central or western regions (all p<0.0001). 32 326 (26%) of 124 274 HBsAg-positive men tested positive for HBeAg (suggesting high infectiousness); this decreased with increasing age (p<0.0001). INTERPRETATION: HBV prevalence in men in rural China has changed from highly endemic into intermediate endemic in the past two decades. However, the absolute number of HBV-infected men and the susceptible population is still very large. FUNDING: Chinese Association of Maternal and Child Health Studies. PMID- 26268689 TI - Assessing tuberculosis management: what really happens to patients? PMID- 26268690 TI - Use of standardised patients to assess quality of tuberculosis care: a pilot, cross-sectional study. AB - BACKGROUND: Existing studies of the quality of tuberculosis care have relied on recall-based patient surveys, questionnaire surveys of knowledge, and prescription or medical record analysis, and the results mostly show the health care provider's knowledge rather than actual practice. No study has used standardised patients to assess clinical practice. Therefore we aimed to assess quality of care for tuberculosis using such patients. METHODS: We did a pilot, cross-sectional validation study of a convenience sample of consenting private health-care providers in low-income and middle-income areas of Delhi, India. We recruited standardised patients in apparently good health from the local community to present four cases (two of presumed tuberculosis and one each of confirmed tuberculosis and suspected multidrug-resistant tuberculosis) to a randomly allocated health-care provider. The key objective was to validate the standardised-patient method using three criteria: negligible risk and ability to avoid adverse events for providers and standardised patients, low detection rates of standardised patients by providers, and data accuracy across standardised patients and audio verification of standardised-patient recall. We also used medical vignettes to assess providers' knowledge of presumed tuberculosis. Correct case management was benchmarked using Standards for Tuberculosis Care in India (STCI). FINDINGS: Between Feb 2, and March 28, 2014, we recruited and trained 17 standardised patients who had 250 interactions with 100 health-care providers, 29 of whom were qualified in allopathic medicine (ie, they had a Bachelor of Medicine & Surgery [MBBS] degree), 40 of whom practised alternative medicine, and 31 of whom were informal health-care providers with few or no qualifications. The interactions took place between April 1, and April 23, 2014. The proportion of detected standardised patients was low (11 [5%] detected out of 232 interactions among providers who completed the follow-up survey), and standardised patients' recall correlated highly with audio recordings (r=0.63 [95% CI 0.53-0.79]), with no safety concerns reported. The mean consultation length was 6 min (95% CI 5.5-6.6) with a mean of 6.18 (5.72-6.64) questions or examinations completed, representing 35% (33-38) of essential checklist items. Across all cases, only 52 (21% [16-26]) of 250 were correctly managed. Correct management was higher among MBBS-qualified doctors than other types of health care provider (adjusted odds ratio 2.41 [95% CI 1.17-4.93]; p=0.0166). Of the 69 providers who completed the vignette, knowledge in the vignettes was more consistent with STCI than their actual clinical practice-eg, 50 (73%) ordered a chest radiograph or sputum test during the vignette compared with seven (10%) during the standardised-patient interaction; OR 0.04 (95% CI 0.02-0.11); p<0.0001. INTERPRETATION: Standardised patients can be successfully implemented to assess tuberculosis care. Our data suggest a big gap between private provider knowledge and practice. Additional work is needed to substantiate our pilot data, understand the know-do gap in provider behaviour, and to identify the best approach to measure and improve the quality of tuberculosis care in India. FUNDING: Grand Challenges Canada, the Bill & Melinda Gates Foundation, Knowledge for Change Program, and the World Bank Development Research Group. PMID- 26268691 TI - Structure, importance and recording of therapeutic information in the medical record: a multicentre observational study. AB - RATIONALE, AIMS AND OBJECTIVES: Structuring the diagnostic section of the medical record (MR) improves diagnosis and communication between doctors. However, little is known about the therapeutic section of the MR. The aim of this study was to gain insight into the extent to which MRs are structured for therapeutic information, to determine which therapeutic data registrars and clinical consultants consider should be recorded in the MR and to what extent registrars record this information themselves. METHODS: A multicentre observational study was carried out in the internal medicine outpatient clinics of five teaching hospitals in the Netherlands. Preformatted structure, importance and actual recording of therapeutic information was compared with a reference list of 35 therapeutic items based on the WHO Guide to Good Prescribing (e.g. drug name, indication for drug). RESULTS: The preformatted structure of four paper MRs and one electronic MR was assessed. Eight of the 35 therapeutic items were listed in the paper MRs and 18 items in the electronic MR. Registrars and consultants agreed on the importance of recording most of the therapeutic items in the MR, 25 and 27 out of the 35 items, respectively; however, registrars recorded only 11 of the 35 items in the paper MR and 20 of the 35 items in the electronic MR. CONCLUSIONS: The structure and content of paper and electronic MRs are not adequate. While both registrars and consultants agree on the importance of recording therapeutic items in the MR, registrars fail to record most of this information in practice. The results of this study can be used as starting point for the discussion regarding the necessity of structured recording of therapeutic information in the MR and its possible benefits with regard to medication safety and training of the new generation of prescribers. PMID- 26268693 TI - Automatic muscle and fat segmentation in the thigh from T1-Weighted MRI. AB - PURPOSE: To introduce and validate an automatic segmentation method for the discrimination of skeletal muscle (SM), and adipose tissue (AT) components (subcutaneous adipose tissue [SAT] and intermuscular adipose tissue [IMAT]) from T1-weighted (T1 -W) magnetic resonance imaging (MRI) images of the thigh. MATERIALS AND METHODS: Eighteen subjects underwent an MRI examination on a 1.5T Philips Achieva scanner. Acquisition was performed using a T1 -W sequence (TR = 550 msec, TE = 15 msec), pixel size between 0.81-1.28 mm, slice thickness of 6 mm. Bone, AT, and SM were discriminated using a fuzzy c-mean algorithm and morphologic operators. The muscle fascia that separates SAT from IMAT was detected by integrating a morphological-based segmentation with an active contour Snake. The method was validated on five young normal weight, five older normal weight, and five older obese females, comparing automatic with manual segmentations. RESULTS: We reported good performance in the extraction of SM, AT, and bone in each subject typology (mean sensitivity above 96%, mean relative area difference of 1.8%, 2.7%, and 2.5%, respectively). A mean distance between contours pairs of 0.81 mm and a mean percentage of contour points with distance smaller than 2 pixels of 86.2% were obtained in the muscle fascia identification. Significant correlation was also found between manual and automatic IMAT and SAT cross-sectional areas in all subject typologies (p < 0.001). CONCLUSION: The proposed automatic segmentation approach provides adequate thigh tissue segmentation and may be helpful in studies of regional composition. PMID- 26268694 TI - Development and testing of indicators to measure coordination of clinical information and management across levels of care. AB - BACKGROUND: Coordination across levels of care is becoming increasingly important due to rapid advances in technology, high specialisation and changes in the organization of healthcare services; to date, however, the development of indicators to evaluate coordination has been limited. The aim of this study is to develop and test a set of indicators to comprehensively evaluate clinical coordination across levels of care. METHODS: A systematic review of literature was conducted to identify indicators of clinical coordination across levels of care. These indicators were analysed to identify attributes of coordination and classified accordingly. They were then discussed within an expert team and adapted or newly developed, and their relevance, scientific soundness and feasibility were examined. The indicators were tested in three healthcare areas of the Catalan health system. RESULTS: 52 indicators were identified addressing 11 attributes of clinical coordination across levels of care. The final set consisted of 21 output indicators. Clinical information transfer is evaluated based on information flow (4) and the adequacy of shared information (3). Clinical management coordination indicators evaluate care coherence through diagnostic testing (2) and medication (1), provision of care at the most appropriate level (2), completion of diagnostic process (1), follow-up after hospital discharge (4) and accessibility across levels of care (4). The application of indicators showed differences in the degree of clinical coordination depending on the attribute and area. CONCLUSION: A set of rigorous and scientifically sound measures of clinical coordination across levels of care were developed based on a literature review and discussion with experts. This set of indicators comprehensively address the different attributes of clinical coordination in main transitions across levels of care. It could be employed to identify areas in which health services can be improved, as well as to measure the effect of efforts to improve clinical coordination in healthcare organizations. PMID- 26268692 TI - Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies. AB - OBJECTIVE: To systematically review associations between intake of saturated fat and trans unsaturated fat and all cause mortality, cardiovascular disease (CVD) and associated mortality, coronary heart disease (CHD) and associated mortality, ischemic stroke, and type 2 diabetes. DESIGN: Systematic review and meta analysis. DATA SOURCES: Medline, Embase, Cochrane Central Registry of Controlled Trials, Evidence-Based Medicine Reviews, and CINAHL from inception to 1 May 2015, supplemented by bibliographies of retrieved articles and previous reviews. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Observational studies reporting associations of saturated fat and/or trans unsaturated fat (total, industrially manufactured, or from ruminant animals) with all cause mortality, CHD/CVD mortality, total CHD, ischemic stroke, or type 2 diabetes. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and assessed study risks of bias. Multivariable relative risks were pooled. Heterogeneity was assessed and quantified. Potential publication bias was assessed and subgroup analyses were undertaken. The GRADE approach was used to evaluate quality of evidence and certainty of conclusions. RESULTS: For saturated fat, three to 12 prospective cohort studies for each association were pooled (five to 17 comparisons with 90,501-339,090 participants). Saturated fat intake was not associated with all cause mortality (relative risk 0.99, 95% confidence interval 0.91 to 1.09), CVD mortality (0.97, 0.84 to 1.12), total CHD (1.06, 0.95 to 1.17), ischemic stroke (1.02, 0.90 to 1.15), or type 2 diabetes (0.95, 0.88 to 1.03). There was no convincing lack of association between saturated fat and CHD mortality (1.15, 0.97 to 1.36; P=0.10). For trans fats, one to six prospective cohort studies for each association were pooled (two to seven comparisons with 12,942-230,135 participants). Total trans fat intake was associated with all cause mortality (1.34, 1.16 to 1.56), CHD mortality (1.28, 1.09 to 1.50), and total CHD (1.21, 1.10 to 1.33) but not ischemic stroke (1.07, 0.88 to 1.28) or type 2 diabetes (1.10, 0.95 to 1.27). Industrial, but not ruminant, trans fats were associated with CHD mortality (1.18 (1.04 to 1.33) v 1.01 (0.71 to 1.43)) and CHD (1.42 (1.05 to 1.92) v 0.93 (0.73 to 1.18)). Ruminant trans-palmitoleic acid was inversely associated with type 2 diabetes (0.58, 0.46 to 0.74). The certainty of associations between saturated fat and all outcomes was "very low." The certainty of associations of trans fat with CHD outcomes was "moderate" and "very low" to "low" for other associations. CONCLUSIONS: Saturated fats are not associated with all cause mortality, CVD, CHD, ischemic stroke, or type 2 diabetes, but the evidence is heterogeneous with methodological limitations. Trans fats are associated with all cause mortality, total CHD, and CHD mortality, probably because of higher levels of intake of industrial trans fats than ruminant trans fats. Dietary guidelines must carefully consider the health effects of recommendations for alternative macronutrients to replace trans fats and saturated fats. PMID- 26268695 TI - Evidence for the involvement of cofilin in Aspergillus fumigatus internalization into type II alveolar epithelial cells. AB - BACKGROUND: The internalization of Aspergillus fumigatus into alveolar epithelial cells (AECs) is tightly controlled by host cellular actin dynamics, which require close modulation of the ADF (actin depolymerizing factor)/cofilin family. However, the role of cofilin in A. fumigatus internalization into AECs remains unclear. RESULTS: Here, we demonstrated that germinated A. fumigatus conidia were able to induce phosphorylation of cofilin in A549 cells during the early stage of internalization. The modulation of cofilin activity by overexpression, knockdown, or mutation of the cofilin gene in A549 cells decreased the efficacy of A. fumigatus internalization. Reducing the phosphorylation status of cofilin with BMS-5 (LIM kinase inhibitor) or overexpression of the slingshot phosphatases also impeded A. fumigatus internalization. Both the C. botulimun C3 transferase (a specific RhoA inhibitor) and Y27632 (a specific ROCK inhibitor) reduced the internalization of A. fumigatus and the level of phosphorylated cofilin. beta-1,3 glucan (the major component of the conidial cell wall) and its host cell receptor dectin-1 did not seem to be associated with cofilin phosphorylation during A. fumigatus infection. CONCLUSION: These results indicated that cofilin might be involved in the modulation of A. fumigatus internalization into type II alveolar epithelial cells through the RhoA-ROCK-LIM kinase pathway. PMID- 26268697 TI - Bilateral breast cancer, synchronous and metachronous; differences and outcome. AB - The aims of this study were twofold: to analyze the incidence of patients having synchronous or metachronous bilateral invasive breast cancer (SBBC and MBBC) and to assess the characteristics and outcome compared to those having unilateral breast cancer (UBC). The used data were obtained from our prospective population based cohort study which had been started in 1983. Bilateral breast cancer (BBC) was categorized as SBBC (<=3 months of the first primary) or MBBC (>3 months after the first primary). The incidence of SBBC was 1% and that of MBBC 7.0 %. Patients with UBC showed more ductal carcinoma compared to patients with BBC. MBBC status was an independent significant predictor of local failure (HR 1.9; 95% CI 1.3-2.7). SBBC status was an independent predictor of distant metastases (HR 2.6; 95% CI 1.4-4.5). Overall survival (OS) was better for MBBC (HR 0.6; 95% CI 0.4-0.8) and worse for SBBC (HR 2.3; 95% CI 1.5-3.6) compared to UBC. We noted: (1) MBBC showed a significant higher local failure compared to UBC, (2) SBBC, compared to MBBC and UBC had a significant higher distant metastases rate, (3) disease-specific survival and OS were significantly worse for SBBC compared to UBC and MBBC, and (4) that the OS for MBBC compared to UBC, was significantly better. PMID- 26268696 TI - TMEM33: a new stress-inducible endoplasmic reticulum transmembrane protein and modulator of the unfolded protein response signaling. AB - Endoplasmic reticulum (ER) stress leads to activation of the unfolded protein response (UPR) signaling cascade and induction of an apoptotic cell death, autophagy, oncogenesis, metastasis, and/or resistance to cancer therapies. Mechanisms underlying regulation of ER transmembrane proteins PERK, IRE1alpha, and ATF6alpha/beta, and how the balance of these activities determines outcome of the activated UPR, remain largely unclear. Here, we report a novel molecule transmembrane protein 33 (TMEM33) and its actions in UPR signaling. Immunoblotting and northern blot hybridization assays were used to determine the effects of ER stress on TMEM33 expression levels in various cell lines. Transient transfections, immunofluorescence, subcellular fractionation, immunoprecipitation, and immunoblotting were used to study the subcellular localization of TMEM33, the binding partners of TMEM33, and the expression of downstream effectors of PERK and IRE1alpha. Our data demonstrate that TMEM33 is a unique ER stress-inducible and ER transmembrane molecule, and a new binding partner of PERK. Exogenous expression of TMEM33 led to increased expression of p eIF2alpha and p-IRE1alpha and their known downstream effectors, ATF4-CHOP and XBP1-S, respectively, in breast cancer cells. TMEM33 overexpression also correlated with increased expression of apoptotic signals including cleaved caspase-7 and cleaved PARP, and an autophagosome protein LC3II, and reduced expression of the autophagy marker p62. TMEM33 is a novel regulator of the PERK eIE2alpha-ATF4 and IRE1-XBP1 axes of the UPR signaling. Therefore, TMEM33 may function as a determinant of the ER stress-responsive events in cancer cells. PMID- 26268699 TI - A method for the evaluation of thousands of automated 3D stem cell segmentations. AB - There is no segmentation method that performs perfectly with any dataset in comparison to human segmentation. Evaluation procedures for segmentation algorithms become critical for their selection. The problems associated with segmentation performance evaluations and visual verification of segmentation results are exaggerated when dealing with thousands of three-dimensional (3D) image volumes because of the amount of computation and manual inputs needed. We address the problem of evaluating 3D segmentation performance when segmentation is applied to thousands of confocal microscopy images (z-stacks). Our approach is to incorporate experimental imaging and geometrical criteria, and map them into computationally efficient segmentation algorithms that can be applied to a very large number of z-stacks. This is an alternative approach to considering existing segmentation methods and evaluating most state-of-the-art algorithms. We designed a methodology for 3D segmentation performance characterization that consists of design, evaluation and verification steps. The characterization integrates manual inputs from projected surrogate 'ground truth' of statistically representative samples and from visual inspection into the evaluation. The novelty of the methodology lies in (1) designing candidate segmentation algorithms by mapping imaging and geometrical criteria into algorithmic steps, and constructing plausible segmentation algorithms with respect to the order of algorithmic steps and their parameters, (2) evaluating segmentation accuracy using samples drawn from probability distribution estimates of candidate segmentations and (3) minimizing human labour needed to create surrogate 'truth' by approximating z stack segmentations with 2D contours from three orthogonal z-stack projections and by developing visual verification tools. We demonstrate the methodology by applying it to a dataset of 1253 mesenchymal stem cells. The cells reside on 10 different types of biomaterial scaffolds, and are stained for actin and nucleus yielding 128 460 image frames (on average, 125 cells/scaffold * 10 scaffold types * 2 stains * 51 frames/cell). After constructing and evaluating six candidates of 3D segmentation algorithms, the most accurate 3D segmentation algorithm achieved an average precision of 0.82 and an accuracy of 0.84 as measured by the Dice similarity index where values greater than 0.7 indicate a good spatial overlap. A probability of segmentation success was 0.85 based on visual verification, and a computation time was 42.3 h to process all z-stacks. While the most accurate segmentation technique was 4.2 times slower than the second most accurate algorithm, it consumed on average 9.65 times less memory per z-stack segmentation. PMID- 26268698 TI - Full engagement of liganded maltose-binding protein stabilizes a semi-open ATP binding cassette dimer in the maltose transporter. AB - MalFGK2 is an ATP-binding cassette (ABC) transporter that mediates the uptake of maltose/maltodextrins into Escherichia coli. A periplasmic maltose-binding protein (MBP) delivers maltose to the transmembrane subunits (MalFG) and stimulates the ATPase activity of the cytoplasmic nucleotide-binding subunits (MalK dimer). This MBP-stimulated ATPase activity is independent of maltose for purified transporter in detergent micelles. However, when the transporter is reconstituted in membrane bilayers, only the liganded form of MBP efficiently stimulates its activity. To investigate the mechanism of maltose stimulation, electron paramagnetic resonance spectroscopy was used to study the interactions between the transporter and MBP in nanodiscs and in detergent. We found that full engagement of both lobes of maltose-bound MBP unto MalFGK2 is facilitated by nucleotides and stabilizes a semi-open MalK dimer. Maltose-bound MBP promotes the transition to the semi-open state of MalK when the transporter is in the membrane, whereas such regulation does not require maltose in detergent. We suggest that stabilization of the semi-open MalK2 conformation by maltose-bound MBP is key to the coupling of maltose transport to ATP hydrolysis in vivo, because it facilitates the progression of the MalK dimer from the open to the semi-open conformation, from which it can proceed to hydrolyze ATP. PMID- 26268700 TI - BRAF V600E mutation: Differential impact on central lymph node metastasis by tumor size in papillary thyroid carcinoma. AB - BACKGROUND: The necessity of prophylactic central neck dissection is one of debating issues in the treatment of papillary thyroid carcinoma (PTC). In a previous study, the predictive value of BRAF mutation for lymph node metastasis was only significant in 0.5 to 1.0 cm PTC. Thus, we assess the predictive value of BRAF mutation for central lymph node metastasis according to tumor size. METHODS: Medical records of 3107 patients with PTC who underwent thyroidectomy with central neck dissection were retrospectively reviewed. RESULTS: BRAF mutation was a predictor for central lymph node metastasis in 2.0 to 4.0 cm PTC (odds ratio [OR] = 3.494; p = .002). Although BRAF mutation was associated with central lymph node metastasis in 0.5 to 1.0 cm PTC in univariate analysis (OR = 1.334; p = .047), this significance was not observed in multivariate analysis (OR = 1.232; p = .163). BRAF mutation was not associated with central lymph node metastasis in other tumor sizes. CONCLUSION: Prophylactic central neck dissection could be considered in 2.0 to 4.0 cm PTC with positive BRAF mutation. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1203-E1209, 2016. PMID- 26268701 TI - The burden among family caregivers of elderly cancer patients: prospective study in a Moroccan population. AB - BACKGROUND: In Morocco, families play a major role in caring for elderly cancer patients. METHODS: We conducted a prospective descriptive study, in the National Institute of Oncology in Morocco. The study aimed to include family members who are caregivers for patients aged >=70 years old. FINDINGS: After obtaining IRB approval, a total of 150 caregivers responded to the questionnaire. Mean age was 44.7 years. The majority were females (59.3%), living in urban areas (66.7%), and educated (62.7%).Offspring (sons or daughters) represented 56.7, 54% lived with their relatives in the same house. Most of the participants were married and have familial responsibilities. In relatives, anxiety was found in 79.3%, it was related to fear of losing the patient in 57% and resulted in the use of anxiolytics in 10%. Guilt feeling towards patients regarding neglecting their early symptoms was reported in 38%. Depression and anxiety were more frequent among female relatives and among those of urban origin. Obsession of dying from cancer was present in about 30% and fear of contagion was more common among those from rural areas and illiterate. Economic resources were exceeded in 78.7 and 56% have used banking credits, and sale of properties. Work lay-off was recorded in 54%. Relatives participated in treatment making decisions in 86% of patients. CONCLUSION: Even there was a great impact on elderly cancerous patients relatives, the benefits of caregiving was observed in 80%. More studies have to be conducted, especially in developing countries where the lack of resources majors the impact on family caregivers. PMID- 26268702 TI - Postnatal retention in HIV care: insight from the Swiss HIV Cohort Study over a 15-year observational period. AB - OBJECTIVES: The aim of this study was to quantify loss to follow-up (LTFU) in HIV care after delivery and to identify risk factors for LTFU, and implications for HIV disease progression and subsequent pregnancies. METHODS: We used data on pregnancies within the Swiss HIV Cohort Study from 1996 to 2011. A delayed clinical visit was defined as > 180 days and LTFU as no visit for > 365 days after delivery. Logistic regression analysis was used to identify risk factors for LTFU. RESULTS: A total of 695 pregnancies in 580 women were included in the study, of which 115 (17%) were subsequent pregnancies. Median maternal age was 32 years (IQR 28-36 years) and 104 (15%) women reported any history of injecting drug use (IDU). Overall, 233 of 695 (34%) women had a delayed visit in the year after delivery and 84 (12%) women were lost to follow-up. Being lost to follow-up was significantly associated with a history of IDU [adjusted odds ratio (aOR) 2.79; 95% confidence interval (CI) 1.32-5.88; P = 0.007] and not achieving an undetectable HIV viral load (VL) at delivery (aOR 2.42; 95% CI 1.21-4.85; P = 0.017) after adjusting for maternal age, ethnicity and being on antiretroviral therapy (ART) at conception. Forty-three of 84 (55%) women returned to care after LTFU. Half of them (20 of 41) with available CD4 had a CD4 count < 350 cells/MUL and 15% (six of 41) a CD4 count < 200 cells/MUL at their return. CONCLUSIONS: A history of IDU and detectable HIV VL at delivery were associated with LTFU. Effective strategies are warranted to retain women in care beyond pregnancy and to avoid CD4 cell count decline. ART continuation should be advised especially if a subsequent pregnancy is planned. PMID- 26268704 TI - Erratum: Pregnancy complications and birth outcomes among women experiencing nausea only or nausea and vomiting during pregnancy in the Norwegian Mother and Child Cohort Study. PMID- 26268705 TI - Abnormal cervical cytology and health care use: a population-based register study. AB - OBJECTIVE: This study aimed to assess the long-term use of health care services in women with abnormal cytology results compared to women with normal cytology results. METHODS: We did a nationwide population-based study, using women aged 23 to 59years participating in the national organized cervical cancer screening program. We included a study population of 40,153 women with abnormal cytology (exposed) and 752,627 women with normal cytology (non-exposed). We retrieved data from the Danish Civil Registration System, the Danish Pathology Data Bank, the National Health Service, the National Patient and the National Prescription Register. We calculated the frequencies of contacts to general practitioner (GP), to private psychiatrist and/or psychologist, admissions to hospitals and use of prescription drugs. These frequencies were calculated separately in the 5-year period "before" the cytology result and for the 5-year period "after" the result. RESULTS: During the "before" period exposed women had more contacts to GPs, more contacts to psychologists/psychiatrist, and more hospital admissions than non exposed women. In both exposed and non-exposed women, health care use increased from the "before" to the "after" period. This increase was significantly higher for exposed than non-exposed women regarding contacts to GP, admissions to hospitals, and drug use. CONCLUSION: Women with abnormal cytology results constitute a selected group with a higher health care use than other women even before they have the abnormal cytology. This difference is further enhanced after the abnormal cytology result. PMID- 26268703 TI - Elevated beta-catenin pathway as a novel target for patients with resistance to EGF receptor targeting drugs. AB - There is a high death rate of lung cancer patients. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are effective in some lung adenocarcinoma patients with EGFR mutations. However, a significant number of patients show primary and acquire resistance to EGFR-TKIs. Although the Akt kinase is commonly activated due to various resistance mechanisms, the key targets of Akt remain unclear. Here, we show that the Akt-beta-catenin pathway may be a common resistance mechanism. We analyzed gene expression profiles of gefitinib-resistant PC9M2 cells that were derived from gefitinib-sensitive lung cancer PC9 cells and do not have known resistance mechanisms including EGFR mutation T790M. We found increased expression of Axin, a beta-catenin target gene, increased phosphorylation of Akt and GSK3, accumulation of beta-catenin in the cytoplasm/nucleus in PC9M2 cells. Both knockdown of beta-catenin and treatment with a beta-catenin inhibitor at least partially restored gefitinib sensitivity to PC9M2 cells. Lung adenocarcinoma tissues derived from gefitinib resistant patients displayed a tendency to accumulate beta-catenin in the cytoplasm. We provide a rationale for combination therapy that includes targeting of the Akt-beta-catenin pathway to improve the efficacy of EGFR-TKIs. PMID- 26268706 TI - En face optical coherence tomography and angiography of talc retinopathy. PMID- 26268707 TI - An assessment of the test-retest reliability of the New Nordic Diet score. AB - BACKGROUND: There is a growing interest in the New Nordic Diet (NND) as a potentially health promoting, environmentally friendly, and palatable regional diet. Also, dietary scores are gaining ground as a complementary approach for examining relations between dietary patterns and various health outcomes. A score assessing adherence to the NND has earlier been published, yet not tested for reliability. OBJECTIVE: To assess the test-retest reliability of the NND score in a sample of parents of toddlers, residing in Southern Norway. DESIGN: A questionnaire survey was completed on two occasions, approximately 14 days apart, by 67 parents of toddlers [85% females, mean age 34 years (SD=5.3 years)]. The NND score was constructed from 24 items and comprised 10 subscales that summarize meal pattern and intake of typical Nordic foods. Each subscale was dichotomized by the median and assigned values of '0' or '1'. Adding the subscales yielded a score ranging from 0 to 10, which was further trichotomized. Test-retest reliability of the final NND score and individual subscales was assessed by Pearson's correlation coefficient and Spearman's rank correlation coefficient, respectively. Additionally, cross tabulation and kappa measure of agreement (k) were used to assess the test-retest agreement of classification into the NND score, and the subscales. RESULTS: Test-retest correlations of the NND score and subscales were r=0.80 (Pearson) and r=0.54-0.84 (Spearman), respectively, all p<0.001. There were 69% (k=0.52) and 67-88% (k=0.32-0.76) test-retest correct classification of the trichotomized score and the dichotomized subscales, respectively. CONCLUSION: The NND score and the 10 subscales appear to have acceptable test-retest reliability when tested in a sample of parents of toddlers. PMID- 26268708 TI - Studying the effects of dietary body weight-adjusted acute tryptophan depletion on punishment-related behavioral inhibition. AB - BACKGROUND: Alterations in serotonergic (5-HT) neurotransmission are thought to play a decisive role in affective disorders and impulse control. OBJECTIVE: This study aims to reproduce and extend previous findings on the effects of acute tryptophan depletion (ATD) and subsequently diminished central 5-HT synthesis in a reinforced categorization task using a refined body weight-adjusted depletion protocol. DESIGN: Twenty-four young healthy adults (12 females, mean age [SD]=25.3 [2.1] years) were subjected to a double-blind within-subject crossover design. Each subject was administered both an ATD challenge and a balanced amino acid load (BAL) in two separate sessions in randomized order. Punishment-related behavioral inhibition was assessed using a forced choice go/no-go task that incorporated a variable payoff schedule. RESULTS: Administration of ATD resulted in significant reductions in TRP measured in peripheral blood samples, indicating reductions of TRP influx across the blood-brain barrier and related brain 5-HT synthesis. Overall accuracy and response time performance were improved after ATD administration. The ability to adjust behavioral responses to aversive outcome magnitudes and behavioral adjustments following error contingent punishment remained intact after decreased brain 5-HT synthesis. A previously observed dissociation effect of ATD on punishment-induced inhibition was not observed. CONCLUSIONS: Our results suggest that neurodietary challenges with ATD Moja-De have no detrimental effects on task performance and punishment-related inhibition in healthy adults. PMID- 26268709 TI - Bleeding complications in cholecystectomy: a register study of over 22,000 cholecystectomies in Finland. AB - BACKGROUND: Major bleeding is rare but among the most serious complications of laparoscopic surgery. Still very little is known on bleeding complications and related blood component use in laparoscopic cholecystectomy (LC). The aim of this study is to compare bleeding complications, transfusion rates and related costs between LC and open cholecystectomy (OC). METHODS: Data concerning LCs and OCs and related blood component use between 2002 and 2007 were collected from existing computerized medical records (Finnish Red Cross Register) of ten Finnish hospital districts. RESULTS: Register data included 17175 LCs and 4942 OCs. In the LC group, 1.3% of the patients received red blood cell (RBC) transfusion compared to 13% of the patients in the OC group (p < 0.001). Similarly, the proportions of patients with platelet (0.1% vs. 1.2%, p < 0.001) and fresh frozen plasma (FFP) products (0.5% vs. 5.8%) transfusions were respectively higher in the OC group than in the LC group. The mean transfused dose of RBCs, PTLs and FFP product Octaplas or the mean cost of the transfused blood components did not differ significantly between the LC and OC groups. CONCLUSIONS: Laparoscopic cholecystectomy was associated with lower transfusion rates of blood components compared to open surgery. The severity of bleeding complications may not differ substantially between LC and OC. PMID- 26268710 TI - The diagnostic value of contrast-enhanced ultrasound in differentiating small renal carcinoma and angiomyolipoma. AB - The aim of this study was to explore the value of contrast-enhanced ultrasound (CEUS) in differentiating small renal masses. A total of 102 small renal masses (<= 3 cm) in 99 patients were examined using conventional ultrasound (CUS) and CEUS, and the findings were reviewed and evaluated in comparison to pathology. Significant differences between renal cell carcinomas (RCCs) and angiomyolipomas (AMLs) were noted in terms of the orientation and echogenicity on CUS (p < 0.05 for both), but the location, shape, margins, homogeneity, and blood flow signals of RCCs on color Doppler flow imaging (CDFI) were similar to those of AMLs (p > 0.05 for all). On CEUS, however, the enhancement intensity, washout in the late phase, and perilesional rim-like enhancement differed significantly for RCCs and AMLs (p = 0.000 for all). Significant differences between CEUS and CUS in terms of sensitivity (88.9% vs. 55.6%), the negative predictive value (68.0% vs. 29.5%), the false negative rate (9.9% vs. 44.5%), and accuracy (88.3% vs. 58.9%) were noted (p < 0.05 for all). CEUS, with its unique features, has value in diagnosing small RCCs and AMLs and outperforms CUS in differentiation of small RCCs and AMLs. PMID- 26268711 TI - Valve-in-valve using an Edwards Sapien XT into a JenaValve in a patient with a low originating left coronary artery and a heavily calcified aorta. AB - Coronary obstruction during transcatheter aortic valve implantation is a potentially life-threatening complication. Most of the widely used transcatheter heart valves require a certain distance between the basal aortic annular plane and the origins of the coronary arteries. We report the case of a successful valve-in-valve procedure with an Edwards SAPIEN XT valve into a JenaValve as a bail-out procedure in a patient with a low originating left coronary artery and a heavily calcified aorta. PMID- 26268712 TI - Increased psychosocial risk, depression and reduced quality of life living with autosomal dominant polycystic kidney disease. AB - BACKGROUND: The psychosocial impact of living with autosomal dominant polycystic kidney disease (ADPKD) is poorly understood. In this study, we assessed the overall quality of life (QOL), mood, perceived social support and psychosocial risk of having a diagnosis of ADPKD in a patient cohort from a major UK nephrology centre serving a large catchment population. METHODS: A postal questionnaire was sent to 349 patients registered at the Sheffield Kidney Institute with chronic kidney disease but not on renal replacement therapy (RRT). The questionnaire incorporated three validated forms: kidney disease quality-of life short form (KDQOL SF1.3) to assess QOL; nine-item patient health questionnaire (PHQ9) to screen for depression; multidimensional scale of perceived social support (MSPSS) to evaluate perceived social support; as well as a novel genetic psychosocial risk instrument (GPRI-ADPKD) designed to study the specific psychosocial impact of coping with a diagnosis of ADPKD. RESULTS: The overall response rate was 53%. Patients with a lower estimated glomerular filtration rate (<30 mL/min) or larger kidneys (mean length on ultrasound >=17 cm) reported reduced QOL and increased psychosocial risk. Clinically significant depression was reported in 22% and 62% felt guilty about passing ADPKD on to their children. In multivariate analysis, female gender was associated with overall poorer psychosocial well-being, whereas increasing age, lower kidney function, larger kidneys and loss of a first degree relative from ADPKD were additional risk factors for QOL, depression or psychosocial risk, respectively. CONCLUSIONS: Our results reveal a significantly poorer QOL and increasing psychosocial risk with markers of disease progression in patients, particularly women, with ADPKD prior to starting RRT. The future management strategy of ADPKD should address these issues and provide for better individual and family support throughout the patient journey. PMID- 26268713 TI - Nephrologists' perceptions regarding dialysis withdrawal and palliative care in Europe: lessons from a European Renal Best Practice survey. AB - BACKGROUND: There is a variation in dialysis withdrawal rates, but reasons for this variation across European countries are largely unknown. We therefore surveyed nephrologists' perceptions of factors concerning dialysis withdrawal and palliative care and explored relationships between these perceptions and reports of whether withdrawal actually occurred in practice. METHODS: We developed a 33 item electronic survey, disseminated via an email blast to all European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) members. In our data analyses, we distinguished those respondents who reported occurrence from those reporting no dialysis withdrawal in their unit. With multilevel logistic regression, we investigated the association between respondents' characteristics and perceptions and whether they reported occurrence of dialysis withdrawal or not. RESULTS: Five hundred and twenty-eight nephrologists from 45 countries completed the questionnaire; 42% reported occurrence of withdrawal in their unit in the past year, and 56% perceived that stopping life-prolonging treatment in terminally ill patients was allowed. Few respondents reported presence in their unit of protocols on withdrawal decision making (7%) or palliative care (10%) or the common involvement of a geriatrician in withdrawal decisions (10%). The majority stated that palliative care had not been part of their core curriculum (74%) and that they had not recently attended continuous medical education sessions on this topic (73%). Respondents from Eastern and Southern Europe had a 42 and 40% lower probability, respectively, of reporting withdrawal compared with those from North European countries. Working in a public centre [odds ratio (OR), 2.41; 95% confidence interval (CI), 1.36-4.25] and respondents' perception that stopping life-prolonging treatment in terminally ill patients was allowed (OR, 1.96; 95% CI, 1.23-3.12), that withdrawal decisions were commonly shared between doctor and patient (OR, 1.97; 95% CI, 1.26-3.08) and that palliative care was reimbursed (OR, 1.81; 95% CI, 1.16-2.83) increased the odds of reporting occurrence of withdrawal. CONCLUSION: Reports of dialysis withdrawal occurrence varied between European countries. Occurrence reports were more likely if respondents worked in a public centre, if stopping life-prolonging treatments was perceived as allowed, if withdrawal decisions were considered shared between doctors and patients and if reimbursement of palliative care was believed to be in place. There is room for improvement regarding protocols on withdrawal and palliative care processes and regarding nephrologists' training and education on end-of-life care. PMID- 26268714 TI - Economic impact of a modification of the treatment trajectories of patients with end-stage renal disease. AB - BACKGROUND: This study assumed that some patients currently treated at hospital based haemodialysis centres can be treated with another renal replacement therapy (RRT) modality without any increase in mortality risk and sought to evaluate the monthly cost impact of replacing hospital-based haemodialysis, for which fees are highest, by different proportions of other modalities. METHODS: We used a deterministic model tool to predict the outcomes and trajectories of hypothetical cohorts of incident adult end-stage renal disease (ESRD) patients for 15 years of RRT (10 different modalities). Our estimates were based on data from 67 258 patients in the REIN registry and 65 662 patients in the French national health insurance information system. Patients were categorized into six subcohorts, stratified for age and diabetes at ESRD onset, and analyses run for each subcohort. We simulated new strategies of care by changing any or all of the following: initial distributions in treatment modalities, transition rates and some costs. Strategies were classified according to their monthly per-patient cost compared to current practices (cost-minimization analysis). RESULTS: Simulations of the status quo for the next 15 years predicted a per-patient monthly cost of ?2684 for a patient aged 18-45 years without diabetes and ?7361 for one older than 70 years with diabetes. All of the strategies we analysed had monthly per-patient costs lower than the status quo, except for daily home HD. None impaired expected survival. Savings varied by strategy. CONCLUSIONS: Alternative strategies may well be less expensive than current practices. The decision to implement new strategies must nonetheless consider the number of patients concerned, feasibility of renal care reorganization, and investment costs. It must also take into account the role of patients' choice and the availability of professionals. PMID- 26268716 TI - Inflammation and uPAR-Expression in Colorectal Liver Metastases in Relation to Growth Pattern and Neo-adjuvant Therapy. AB - Proteolytic activity and inflammation in the tumour microenvironment affects cancer progression. In colorectal cancer (CRC) liver metastases it has been observed that three different immune profiles are present, as well as proteolytic activity, determined by the expression of urokinase-type plasminogen activator (uPAR).The main objectives of this study were to investigate uPAR expression and the density of macrophages (CD68) and T cells (CD3) as markers of inflammation in resected CRC liver metastases, where patients were neo-adjuvantly treated with chemotherapy with or without the angiogenesis inhibitor bevacizumab. Chemonaive patients served as a control group. The markers were correlated to growth patterns (GP) of liver metastases, i.e. desmoplastic, pushing and replacement GP. It was hypothesised that differences in proteolysis and inflammation could reflect tumour specific growth and therapy related changes in the tumour microenvironment. In chemonaive patients, a significantly higher level of uPAR was observed in desmoplastic liver metastases in comparison to pushing GP (p = 0.01) or replacement GP (p = 0.03). A significantly higher density of CD68 was observed in liver metastases with replacement GP in comparison to those with pushing GP (p = 0.01). In liver metastases from chemo treated patients, CD68 density was significantly higher in desmoplastic GP in comparison to pushing GP (p = 0.03). In chemo and bevacizumab treated patients only a significant lower CD3 expression was observed in liver metastases with a mixed GP than in those with desmoplastic (p = 0.01) or pushing GP (p = 0.05). Expression of uPAR and the density of macrophages at the tumour margin of liver metastasis differ between GP in the untreated patients. A higher density of T cells was observed in the bevacizumab treated patients, when desmoplastic and pushing metastases were compared to liver metastases with a mix of the GP respectively, however no specific correlations between the immune markers of macrophages and T cells or GP of liver metastases could be demonstrated. PMID- 26268717 TI - Blood temperature and perfusion to exercising and non-exercising human limbs. AB - NEW FINDINGS: What is the central question of this study? Temperature-sensitive mechanisms are thought to contribute to blood-flow regulation, but the relationship between exercising and non-exercising limb perfusion and blood temperature is not established. What is the main finding and its importance? The close coupling among perfusion, blood temperature and aerobic metabolism in exercising and non-exercising extremities across different exercise modalities and activity levels and the tight association between limb vasodilatation and increases in plasma ATP suggest that both temperature- and metabolism-sensitive mechanisms are important for the control of human limb perfusion, possibly by activating ATP release from the erythrocytes. Temperature-sensitive mechanisms may contribute to blood-flow regulation, but the influence of temperature on perfusion to exercising and non-exercising human limbs is not established. Blood temperature (TB ), blood flow and oxygen uptake (VO2) in the legs and arms were measured in 16 healthy humans during 90 min of leg and arm exercise and during exhaustive incremental leg or arm exercise. During prolonged exercise, leg blood flow (LBF) was fourfold higher than arm blood flow (ABF) in association with higher TB and limb VO2. Leg and arm vascular conductance during exercise compared with rest was related closely to TB (r(2) = 0.91; P < 0.05), plasma ATP (r(2) = 0.94; P < 0.05) and limb VO2 (r(2) = 0.99; P < 0.05). During incremental leg exercise, LBF increased in association with elevations in TB and limb VO2, whereas ABF, arm TB and VO2 remained largely unchanged. During incremental arm exercise, both ABF and LBF increased in relationship to similar increases in VO2. In 12 trained males, increases in femoral TB and LBF during incremental leg exercise were mirrored by similar pulmonary artery TB and cardiac output dynamics, suggesting that processes in active limbs dominate central temperature and perfusion responses. The present data reveal a close coupling among perfusion, TB and aerobic metabolism in exercising and non-exercising extremities and a tight association between limb vasodilatation and increases in plasma ATP. These findings suggest that temperature and VO2 contribute to the regulation of limb perfusion through control of intravascular ATP. PMID- 26268718 TI - Voltage-responsive reversible self-assembly and controlled drug release of ferrocene-containing polymeric superamphiphiles. AB - A new type of voltage-responsive comb-like superamphiphilic block polymer PEG113 b-PAA30/FTMA was prepared by the electrostatic interactions of an ionic ferrocenyl surfactant (FTMA) and an oppositely charged double-hydrophilic block polyelectrolyte poly-(ethylene glycol)-b-poly(acrylic acid) (PEG113-b-PAA30) in aqueous solution. An in situ electrochemical redox system was designed to research its electrochemical activity in aqueous solution. The polymeric superamphiphile PEG113-b-PAA30/FTMA could reversibly aggregate to form spherical micelles of 20-30 nm diameter in aqueous solution, and also disaggregate into irregular fragments by an electrochemical redox reaction when its concentration is in the range of the critical aggregation concentration (cacred) of the reduction state to its cacox of the oxidation state. Interestingly, above cacox, the superamphiphile can aggregate into spherical micelles of 20-30 nm diameter, which can be transformed into larger spherical micelles of 40-120 nm diameter after electrochemical oxidation, and reversibly recover initial sizes after electrochemical reduction. Moreover, this reversible self-assembly process can be electrochemically controlled just by changing its electrochemical redox extent without adding any other chemical reagent. Further, rhodamine 6G (R6G)-loaded polymeric superamphiphile aggregates have been successfully used for the voltage controlled release of loaded molecules based on their voltage-responsive self assembly, and the release rate of R6G could be mediated by changing electrochemical redox potentials and the concentrations of polymeric superamphiphiles. Our observations witness a new strategy to construct a voltage responsive reversible self-assembly system. PMID- 26268719 TI - Sex Moderates the Effects of the Sorl1 Gene rs2070045 Polymorphism on Cognitive Impairment and Disruption of the Cingulum Integrity in Healthy Elderly. PMID- 26268720 TI - Overexpression of Protein Kinase Mzeta in the Prelimbic Cortex Enhances the Formation of Long-Term Fear Memory. PMID- 26268721 TI - Oral health-related quality of life and complications after treatment with partial removable dental prosthesis. AB - The aims of this study were to measure and describe the oral health-related quality of life (OHRQoL) and to identify the complications caused by partial removable dental prosthesis (RDPs) in patients 1-5 years after treatment. Complications were identified in 65 patients who were treated with 83 RDPs (48 upper, 35 lower). OHRQoL was measured using the OHIP-49 before treatment and at the baseline (1-2 months after treatment) and follow-up (1-5 years after treatment) examinations. The types and numbers of oral problems that were experienced were described based on OHIP items with a score of 3 and 4. A significant improvement (P < 0.05) in the total OHIP-49 was registered from pre treatment (mean 42, SD +/- 37) to baseline (mean 29, SD +/- 27) and from pre treatment to 1-5 years after treatment (mean 32, SD +/- 30). There was no significant difference between the baseline and 1- to 5-year follow-up examinations. Problems with eating and appearance registered at pre-treatment were improved at baseline and after 1-5 years. Problems with dentures that had been registered pre-treatment were improved at baseline but reoccurred after 1-5 years. The two most frequent complications were ill-fitting RDPs and inflammation of the oral mucosa, followed less frequently by fractures of the clasps. Treatment with RDPs improved OHRQoL, but denture-related problems partly remained, and new problems related to RDPs occurred 1-5 years after treatment. The two most frequent complications were ill-fitting RDPs and inflammation of the oral mucosa. PMID- 26268722 TI - Manipulating stomatal density enhances drought tolerance without deleterious effect on nutrient uptake. AB - Manipulation of stomatal density was investigated as a potential tool for enhancing drought tolerance or nutrient uptake. Drought tolerance and soil water retention were assessed using Arabidopsis epidermal patterning factor mutants manipulated to have increased or decreased stomatal density. Root nutrient uptake via mass flow was monitored under differing plant watering regimes using nitrogen 15 ((15) N) isotope and mass spectrometry. Plants with less than half of their normal complement of stomata, and correspondingly reduced levels of transpiration, conserve soil moisture and are highly drought tolerant but show little or no reduction in shoot nitrogen concentrations especially when water availability is restricted. By contrast, plants with over twice the normal density of stomata have a greater capacity for nitrogen uptake, except when water availability is restricted. We demonstrate the possibility of producing plants with reduced transpiration which have increased drought tolerance, with little or no loss of nutrient uptake. We demonstrate that increasing transpiration can enhance nutrient uptake when water is plentiful. PMID- 26268723 TI - A public health e-learning master's programme with a focus on health workforce development targeting francophone Africa: the University of Geneva experience. AB - BACKGROUND: Shortage of a competent public health workforce is as a worldwide problem. The situation is especially bad in sub-Saharan Africa. In 2008, the World Health Organization and the Global Health Workforce Alliance launched a call for proposals for a public health training programme with an emphasis on health workforce development specifically targeting Africa. Our article presents the development, implementation and evaluation of an e-learning Master of Advanced Studies in Public Health on Workforce Development. The project was developed in collaboration with academic partner institutions of 10 French speaking African countries and local/regional/HQ WHO offices. METHODS: A five step approach was adopted. First, a needs assessment study was done in the target countries, with identification of priority health issues. Second, student and tutor selection was done in collaboration with local WHO offices, health authorities and partner universities. Third, the e-platform was developed and a training workshop for tutors was organized. Fourth, the learning objectives were derived from the needs assessment study and an interactive educational approach was adopted. Fifth, the participation of students, their perception of the programme, their performance on assignments and community outcomes were monitored. RESULTS: The needs assessment allowed the identification of 12 priority health issues (trauma related to road accidents, maternal and child health, HIV/AIDS, mental heath, food and malnutrition, health resource management, infectious diseases, access to essential drugs, chronic diseases, health promotion, ageing and violence/conflicts) of which 10 were studied through the lens of the key public health disciplines (epidemiology, human resources, health project/service planning, health policy, communication, health economics/management, informatics and ethics/human rights), each validated through a certifying examination. Student participation, measured through connection hits (total: 58 256; mean: 168/student/module) and posted messages (total: 5994; mean: 18/student/module), was good, and global satisfaction was high (7.7/10). Twenty-nine students out of 37 obtained their master's degree from the University of Geneva. Outcomes reported include career development, strengthening of inter-country networks and common projects. CONCLUSIONS: Keys to the success of the programme were the enthusiasm and commitment of students, the availability of the coordination team, the simplicity of the electronic platform and the support of local/regional/WHO offices. Yet, the sustainability of the programme is not assured. PMID- 26268724 TI - Auxological perspectives on 'growth' in DOHaD. AB - David Barker established growth as a seminal link between early development and later health attainment and disease risk. This was nothing less than a paradigm shift in health and medicine, turning the focus of disease causality away from contemporary environmental influences to earliest growth as a time when functional anatomy and physiology sets in place critical structures and function for a lifetime. Barker's prodigious work investigated time- and place-specific interactions between maternal condition and exogenous environmental influences, focusing on how growth unfolds across development to function as a mechanistic link to ensuing health. Subsequent applications do not always attend to the specificity and sensitivity issues included in his original work, and commonly overlook the long-standing methods and knowledge base of auxology. Methodological areas in need of refinement include enhanced precision in how growth is represented and assessed. For example, multiple variables have been used as a referent for 'growth,' which is problematic because different body dimensions grow by different biological clocks with unique functional physiologies. In addition, categorical clinical variables obscure the spectrum of variability in growth experienced at the individual level. Finally, size alone is a limited measure as it does not capture how individuals change across age, or actually grow. The ground-breaking notion that prenatal influences are important for future health gave rise to robust interest in studying the fetus. Identifying the many pathways by which size is realized permits targeted interventions addressing meaningful mechanistic links between growth and disease risk to promote health across the lifespan. PMID- 26268725 TI - Signatures of natural selection between life cycle stages separated by metamorphosis in European eel. AB - BACKGROUND: Species showing complex life cycles provide excellent opportunities to study the genetic associations between life cycle stages, as selective pressures may differ before and after metamorphosis. The European eel presents a complex life cycle with two metamorphoses, a first metamorphosis from larvae into glass eels (juvenile stage) and a second metamorphosis into silver eels (adult stage). We tested the hypothesis that different genes and gene pathways will be under selection at different life stages when comparing the genetic associations between glass eels and silver eels. RESULTS: We used two sets of markers to test for selection: first, we genotyped individuals using a panel of 80 coding-gene single nucleotide polymorphisms (SNPs) developed in American eel; second, we investigated selection at the genome level using a total of 153,423 RAD sequencing generated SNPs widely distributed across the genome. Using the RAD approach, outlier tests identified a total of 2413 (1.57%) potentially selected SNPs. Functional annotation analysis identified signal transduction pathways as the most over-represented group of genes, including MAPK/Erk signalling, calcium signalling and GnRH (gonadotropin-releasing hormone) signalling. Many of the over represented pathways were related to growth, while others could result from the different conditions that eels inhabit during their life cycle. CONCLUSIONS: The observation of different genes and gene pathways under selection when comparing glass eels vs. silver eels supports the adaptive decoupling hypothesis for the benefits of metamorphosis. Partitioning the life cycle into discrete morphological phases may be overall beneficial since it allows the different life stages to respond independently to their unique selection pressures. This might translate into a more effective use of food and niche resources and/or performance of phase-specific tasks (e.g. feeding in the case of glass eels, migrating and reproducing in the case of silver eels). PMID- 26268726 TI - Evaluating the antidiabetic effects of Chinese herbal medicine: Xiao-Ke-An in 3T3 L1 cells and KKAy mice using both conventional and holistic omics approaches. AB - BACKGROUND: Xiao-Ke-An (XKA) is a Chinese medicine widely used for treating type 2 diabetes mellitus (T2D). It is composed of eight herbal medicines traditionally used for T2D, including Rehmannia glutinosa Libosch, Anemarrhena asphodeloides Bunge, Coptis chinensis Franch, etc. The aim of the present study was to investigate the antidiabetic effects of XKA with both conventional and holistic omics approaches. METHODS: The antidiabetic effect of XKA was first investigated in 3T3-L1 cells to study the effect of XKA on adipogenesis in vitro. Oil Red O staining was performed to determine the lipid accumulation. The intracellular total cholesterol (TC) and triglyceride (TG) contents in XKA treated 3T3-L1 cells were also evaluated. The therapeutic effects of XKA was further evaluated in KKAy mice with both conventional and holistic omics approaches. Body weight, fasting and non-fasting blood glucose, and oral glucose tolerance were measured during the experiment. At the time of sacrifice, serum was collected for the measurement of TG, TC, high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c). The liver, kidney, spleen, pancreas, heart and adipose tissues were harvested and weighted. The liver was used for further microarray experiment. Omics approaches were adopted to evaluate the holistic rebalancing effect of XKA at molecular network level. RESULTS: XKA significantly inhibited adipogenic differentiation, lowered the intracellular TC and TG contents in 3T3-L1 cells. XKA improved the glucose homeostasis and lipid metabolism, ameliorated insulin resistance in KKAy mice. Furthermore, XKA also exhibited effective therapeutic effects by reversing the molecular T2D disease network from an unbalanced state. CONCLUSIONS: This study investigated the antidiabetic effects of XKA with both conventional and holistic omics approaches, providing both phenotypic evidence and underlying action mechanisms for the clinical use of XKA treating T2D. PMID- 26268727 TI - Attenuation of Oxidative Damage by Boerhaavia diffusa L. Against Different Neurotoxic Agents in Rat Brain Homogenate. AB - Due to a high rate of oxidative metabolic activity in the brain, intense production of reactive oxygen metabolite occurs, and the subsequent generation of free radicals is implicated in the pathogenesis of traumatic brain injury, epilepsy, and ischemia as well as chronic neurodegenerative diseases. In the present study, protective effects of polyphenol rich ethanolic extract of Boerhaavia diffusa (BDE), a neuroprotective edible medicinal plant against oxidative stress induced by different neurotoxic agents, were evaluated. BDE was tested against quinolinic acid (QA), 3-nitropropionic acid (NPA), sodium nitroprusside (SNP), and Fe (II)/EDTA complex induced oxidative stress in rat brain homogenates. QA, NPA, SNP, and Fe (II)/EDTA treatment caused an increased level of thiobarbituric acid reactive substances (TBARS) in brain homogenates along with a decline in the activities of antioxidant enzymes. BDE treatment significantly decreased the production of TBARS (p < .05) and increased the activities of antioxidant enzymes like catalase and superoxide dismutase along with increased concentration of non-enzymatic antioxidant, reduced glutathione (GSH). Similarly, BDE caused a significant decrease in the lipid peroxidation (LPO) in the cerebral cortex. Inhibitory potential of BDE against deoxyribose degradation (IC50 value 38.91 +/- 0.12 MUg/ml) shows that BDE can protect hydroxyl radical induced DNA damage in the tissues. Therefore, B. diffusa had high antioxidant potential that could inhibit the oxidative stress induced by different neurotoxic agents in brain. Since many of the neurological disorders are associated with free radical injury, these data may imply that B. diffusa, functioning as an antioxidant agent, may be beneficial for reducing various neurodegenerative complications. PMID- 26268728 TI - Predictors affecting personal health information management skills. AB - OBJECTIVES: This study investigated major factors affecting personal health records (PHRs) management skills associated with survey respondents' health information management related activities. METHODS: A self-report survey was used to assess individuals' personal characteristics, health knowledge, PHR skills, and activities. Factors underlying respondents' current PHR-related activities were derived using principal component analysis (PCA). Scale scores were calculated based on the results of the PCA, and hierarchical linear regression analyses were used to identify respondent characteristics associated with the scale scores. Internal consistency of the derived scale scores was assessed with Cronbach's alpha. RESULTS: Among personal health information activities surveyed (N = 578 respondents), the four extracted factors were subsequently grouped and labeled as: collecting skills (Cronbach's alpha = 0.906), searching skills (Cronbach's alpha = 0.837), sharing skills (Cronbach's alpha = 0.763), and implementing skills (Cronbach's alpha = 0.908). In the hierarchical regression analyses, education and computer knowledge significantly increased the explanatory power of the models. Health knowledge (beta = 0.25, p < 0.001) emerged as a positive predictor of PHR collecting skills. CONCLUSIONS: This study confirmed that PHR training and learning should consider a full spectrum of information management skills including collection, utilization and distribution to support patients' care and prevention continua. PMID- 26268729 TI - Klippel-Trenaunay syndrome belongs to the PIK3CA-related overgrowth spectrum (PROS). AB - Klippel-Trenaunay syndrome (KTS), originally described as a triad of cutaneous capillary malformation, bone and soft-tissue hypertrophy, as well as venous and lymphatic malformations, has been considered by dermatologists as a distinct diagnostic entity. However, cases with KTS have also been reported to have neurological disorders, developmental delay and digital abnormalities, indicating multisystem involvement. Recently, a number of overgrowth syndromes, with overlapping phenotypic features with KTS, have been identified; these include MCAP and CLOVES syndromes as well as fibroadipose hyperplasia. These conditions harbour mutations in the PIK3CA gene, and they have been included in the PIK3CA related overgrowth spectrum (PROS). Based on recent demonstrations of PIK3CA mutations also in KTS, it appears that, rather than being a distinct diagnostic entity, KTS belongs to PROS. These observations have potential diagnostic and therapeutic implications for KTS. PMID- 26268730 TI - Antibiotic Policies and Utilization in Oregon Hospice Programs. AB - Antibiotics are frequently used in hospice care, despite limited data on safety and effectiveness in this patient population. We surveyed Oregon hospice programs on antibiotic policies and prescribing practices. Among 39 responding hospice programs, the median reported proportion of current census using antibiotics was 10% (interquartile range = 3.5%-20.0%). Approximately 31% of responding hospice programs had policies for antibiotic initiation, 17% of hospice programs had policies for antibiotic discontinuation, and 95% of hospice programs had policies for managing drug interactions. Diarrhea, nausea/vomiting, and yeast infections were the most frequently reported antibiotic-associated adverse events, occurring "sometimes" or "often" among 62%, 47%, and 62% of respondents, respectively. In conclusion, less than a third of participating hospice programs reported having a policy for antibiotic initiation and even less frequently a policy for discontinuation. More data are needed on the risks and benefits of antibiotic use in hospice care to inform these policies and optimize outcomes in this vulnerable patient population. PMID- 26268731 TI - Racial Residential Segregation and Disparities in Obesity among Women. AB - The high rate of obesity among black women in the USA is a significant public health problem. However, there is limited research on the relationship between racial residential segregation and disparities in obesity, and the existing evidence is limited and results are mixed. This study examines the relationship between racial residential segregation and obesity among black and white women. We conducted this cross-sectional study by joining data from the 1999-2004 National Health and Nutrition Examination Survey with data from the 2000 US Census. Multilevel logistic regression models found that for every one-point increase in the black isolation index, there was a 1.06 (95 % confidence interval (CI) = 1.01, 1.11) times higher odds of obesity for black women. In order to address the disparately high rates of obesity among black women, health policies need to address the economic, political, and social forces that produce racially segregated neighborhoods. PMID- 26268732 TI - Role of adenosine 5'-monophosphate-activated protein kinase in alpha-linolenic acid-induced intestinal lipid metabolism. AB - n-3 Long-chain PUFA up-regulate intestinal lipid metabolism. However, whether these metabolic effects of PUFA on intestine are mediated by AMP-activated protein kinase (AMPK) remains to be elucidated. To determine the effects of alpha linolenic acid (ALA) on intestinal fatty acid (FA) metabolism and whether these effects were affected by AMPK deletion, mice deficient in the catalytic subunit of AMPKalpha1 or AMPKalpha2 and wild-type (WT) mice were fed either a high-fat diet (HF) or HF supplemented with ALA (HF-A). The results showed that ALA supplementation decreased serum TAG content in WT mice. ALA also increased mRNA expression of genes (carnitine palmitoyltransferase 1a, acyl-CoA oxidase 1, medium-chain acyl-CoA dehydrogenase, cytochrome P450 4A10 and pyruvate dehydrogenase kinase isoenzyme 4a) involved in intestinal lipid oxidation and mRNA expression of TAG synthesis-related genes (monoacylglycerol O acyltransferase 2, diacylglycerol O-acyltransferases 1 and 2) in WT mice. Consistent with these, expression levels of phosphorylated AMPKalpha1 and AMPKalpha2 were also increased in WT mice after ALA addition. However, in the absence of either AMPKalpha1 or AMPKalpha2, ALA supplementation failed to increase intestinal lipid oxidation. In addition, no significant effects of either diet (HF and HF-A) or genotype (WT, AMPKalpha1(-/-) and AMPKalpha2(-/-)) on FA uptake in the intestine and faecal TAG output were observed. Our results suggest that AMPK is indispensable for the effects of ALA on intestinal lipid oxidation. PMID- 26268735 TI - Vaginal Birth After Cesarean (VBAC) Calculator Risks. PMID- 26268733 TI - TRB3 links insulin/IGF to tumour promotion by interacting with p62 and impeding autophagic/proteasomal degradations. AB - High insulin/IGF is a biologic link between diabetes and cancers, but the underlying molecular mechanism remains unclear. Here we report a previously unrecognized tumour-promoting mechanism for stress protein TRB3, which mediates a reciprocal antagonism between autophagic and proteasomal degradation systems and connects insulin/IGF to malignant promotion. We find that several human cancers express higher TRB3 and phosphorylated insulin receptor substrate 1, which correlates negatively with patient's prognosis. TRB3 depletion protects against tumour-promoting actions of insulin/IGF and attenuates tumour initiation, growth and metastasis in mice. TRB3 interacts with autophagic receptor p62 and hinders p62 binding to LC3 and ubiquitinated substrates, which causes p62 deposition and suppresses autophagic/proteasomal degradation. Several tumour-promoting factors accumulate in cancer cells to support tumour metabolism, proliferation, invasion and metastasis. Interrupting TRB3/p62 interaction produces potent antitumour efficacies against tumour growth and metastasis. Our study opens possibility of targeting this interaction as a potential novel strategy against cancers with diabetes. PMID- 26268737 TI - Do different reperfusion methods affect the outcomes of stroke induced by MCAO in adult rats? AB - There are two patterns of ischemia/reperfusion (I/R) models used in rat middle cerebral artery occlusion (MCAO) I/R models, which differ in the use of unilateral or bilateral carotid artery reperfusion. The primary difference between the two patterns of I/R models is the complexity of the surgery procedure. However, researchers in this field have no idea whether there are any differences in outcomes of these two methods. In this study, we investigated the effects of the two methods on neurological deficits, infarct volume, blood-brain barrier (BBB) integrity and brain derived neurotrophic factor (BDNF) expression. Through evaluating the current way of bilateral common carotid artery reperfusion, we tried to find whether it could be replaced by an easier way. We found that there were no statistical significant differences between the different methods in infarct volume, neurological deficits, BBB integrity, and the level of BDNF (P > 0.05). These data demonstrated that different methods did not affect the neurological deficits, infarct volume, BBB integrity, and the BDNF protein level, which provides reference when we use an experimental stroke. These results suggest that the two methods have similar capability for inducing cerebral I/R injury and can be interchanged. PMID- 26268734 TI - Update on CD40 and CD154 blockade in transplant models. AB - Generation of an effective immune response against foreign antigens requires two distinct molecular signals: a primary signal provided by the binding of antigen specific T-cell receptor to peptide-MHC on antigen-presenting cells and a secondary signal delivered via the engagement of costimulatory molecules. Among various costimulatory signaling pathways, the interactions between CD40 and its ligand CD154 have been extensively investigated given their essential roles in the modulation of adaptive immunity. Here, we review current understanding of the role CD40/CD154 costimulation pathway has in alloimmunity, and summarize recent mechanistic and preclinical advances in the evaluation of candidate therapeutic approaches to target this receptor-ligand pair in transplantation. PMID- 26268736 TI - Long-term effects of the multidisciplinary risk assessment and management program for patients with diabetes mellitus (RAMP-DM): a population-based cohort study. AB - BACKGROUND: Studies on the long-term effectiveness of multidisciplinary risk stratification based management in Chinese population were rare. This study aimed to evaluate the effectiveness of a multidisciplinary risk assessment and management program for patients with diabetes mellitus (RAMP-DM) in reducing the risks of cardiovascular complications and all-cause mortality. METHODS: A prospective cohort study was conducted in 18,188 propensity score matched RAMP-DM participants and subjects with diabetes under usual primary care (9,094 subjects in each group). The study endpoints were the first occurrence of coronary heart disease (CHD), stroke, heart failure (HF), total cardiovascular disease (CVD) and all-cause mortality. We constructed multivariable Cox proportional hazard regressions to estimate the association between the RAMP-DM intervention and the first occurrence of study endpoints. RESULTS: The median follow-up period was 36 months. Three hundred and ninety-nine CVD events occurred in the RAMP-DM group, as compared with 608 in the control group [adjusted hazard ratio, 0.629; 95% confidence interval (CI) 0.554-0.715; P < 0.001]. The total number of all-cause deaths in RAMP-DM group was less than half that of control group (202 vs 552, adjusted hazard ratio, 0.363; 95% CI, 0.308-0.428; P < 0.001). The adjusted hazard ratios of the RAMP-DM group for CHD, stroke, and HF were 0.570 (95% CI, 0.470-0.691; P < 0.001), 0.652 (95% CI, 0.546-0.780; P < 0.001), and 0.598 (95%CI, 0.446-0.802; P = 0.001), respectively. CONCLUSIONS: The RAMP-DM intervention was associated with lower incidences of individual and total cardiovascular complications, as well as all-cause mortality over 3 years follow up. The encouraging results provided evidence to support that the structured risk stratification management leading by a multidisciplinary clinical team was an effective approach to reduce future cardiovascular complications in people with diabetes. CLINICAL TRIAL REGISTRY: NCT02034695, http://www.ClinicalTrials.gov. PMID- 26268738 TI - Self-reported insomnia and coronary heart disease in the elderly. AB - OBJECTIVE: We aimed to investigate the association between self-reported insomnia and coronary heart diseases in the elderly Chinese population. METHODS AND RESULTS: A cross-sectional study was conducted in the Beijing and 2982 participants aged >=60 years were recruited. The association between self reported insomnia and coronary heart diseases (CHD) was determined by multiple logistic regression models. Age, gender, education, obesity, physical activity, current smoking, current drinking, medication, hypertension, diabetes, tea consumption, heart rate, and dyslipidemia were adjusted as confounders. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were reported as effect measurements. The numbers of subjects with no insomnia, occasional insomnia, and frequent insomnia were 2110 (70.76%), 509 (17.07%), and 363 (12.17%), respectively. The prevalence of CHD in those with no insomnia, occasional insomnia, and frequent insomnia were 13.65%, 16.31%, and 22.31%. Compared with subjects with no insomnia, the multivariate adjusted ORs and 95% CIs for those with occasional insomnia and frequent insomnia were 1.17 (0.89 1.54) and 1.73 (1.30-2.31), respectively. There was no significant difference of the association between men and women. CONCLUSIONS: Self-reported insomnia is associated with high risks of CHD in the elderly Chinese population. PMID- 26268739 TI - Adjuvant Epidermal Growth Factor Receptor Inhibitors in Non-Small Cell Lung Cancer. PMID- 26268742 TI - Authors' response: British Society of Gastroenterology guidelines on the diagnosis and management of coeliac disease. PMID- 26268740 TI - Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue of the Salivary Glands: A Multicenter, International Experience of 248 Patients (IELSG 41). AB - BACKGROUND: The salivary gland is one of the most common sites involved by nongastric, extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT). A large series of patients with long-term follow-up has not been documented. This multicenter, international study sought to characterize the clinical characteristics, treatment, and natural history of salivary gland MALT lymphoma. METHODS: Patients with biopsy-confirmed salivary gland MALT lymphoma were identified from multiple international sites. Risk factors, treatment, and long-term outcomes were evaluated. RESULTS: A total of 247 patients were evaluated; 76% presented with limited-stage disease. There was a history of autoimmune disorder in 41%, with Sjogren disease being the most common (83%). Fifty-seven percent of patients were initially treated with local therapy with surgery, radiation, or both; 37 of patients were treated with systemic therapy initially, with 47% of those receiving rituximab; and 6% of patients were observed. The median overall survival (OS) was 18.3 years. The median progression free survival (PFS) following primary therapy was 9.3 years. There was no difference in the outcomes between patients receiving local or systemic therapy in first-line management. On multivariate analysis, age <60 years and low to intermediate international prognostic index were associated with improved OS and PFS; Sjogren disease was associated with improved OS. CONCLUSION: Salivary gland MALT lymphoma has an excellent prognosis regardless of initial treatment, and patients with Sjogren disease have improved survival. Risks for long-term complications must be weighed when determining initial therapy. PMID- 26268741 TI - Evaluating Comparative Effectiveness Research Priorities for Care Coordination in Chronic Obstructive Pulmonary Disease: A Community-Based eDelphi Study. AB - BACKGROUND: Despite research supporting the use of care coordination in chronic obstructive pulmonary disease (COPD), there is relatively little known about the comparative effectiveness of different strategies used to organize care for patients. To investigate the most important COPD care coordination strategies, community-based stakeholder input is needed, especially from medically underserved populations. Web-based platforms are electronic tools now being used to bring together individuals from underrepresented populations to share input and obtain clarification on comparative effectiveness research (CER) ideas, questions, and hypotheses. OBJECTIVE: Use low computer-literate, collaborative survey technology to evaluate stakeholder priorities for CER in COPD care coordination. METHODS: A mixed-method, concurrent triangulation design was used to collect survey data from a virtual advisory board of community-based stakeholders including medically underserved patients with COPD, informal caregivers, clinicians, and research scientists. The eDelphi method was used to conduct 3 iterative rounds of Web-based surveys. In the first 2 survey rounds, panelists viewed a series of "mini research prospectus" YouTube video presentations and rated their level of agreement with the importance of 10 COPD care coordination topics using 7-point Likert scales. In the final third-round survey, panelists ranked (1=most important, 8=least important) and commented on 8 remaining topics that panelists favored most throughout the first 2 survey rounds. Following the third-round survey, panelists were asked to provide feedback on the potential impact of a Web-based stakeholder engagement network dedicated to improving CER in COPD. RESULTS: Thirty-seven panelists rated the following care coordination topics as most important (lower means indicate greater importance): (1) measurement of quality of care (mean 2.73, SD 1.95); (2) management of COPD with other chronic health issues (mean 2.92, SD 1.67); (3) pulmonary rehabilitation as a model for care (mean 3.72; SD 1.93); (4) quality of care coordination (mean 4.12, SD 2.41); and (5) comprehensive COPD patient education (mean 4.27, SD 2.38). Stakeholder comments on the relative importance of these care coordination topics primarily addressed the importance of comparing strategies for COPD symptom management and evaluating new methods for patient provider communication. Approximately one half of the virtual panel assembled indicated that a Web-based stakeholder engagement network could enable more online community meetings (n=19/37, 51%) and facilitate more opportunities to suggest, comment on, and vote for new CER ideas in COPD (n=18/37, 49%). CONCLUSIONS: Members of this unique virtual advisory board engaged in a structured Web-based communication process that identified the most important community-specific COPD care coordination research topics and questions. Findings from this study support the need for more CER that evaluates quality of care measures used to assess the delivery of treatments and interventions among medically underserved patients with COPD. PMID- 26268743 TI - Safety and efficacy of TACE and gamma knife on hepatocellular carcinoma with portal vein invasion. PMID- 26268744 TI - Defining dysbiosis threatens Koch's postulates and current dogma on the role of Paneth cells in Crohn's disease. PMID- 26268745 TI - Quantification of mequitazine in human plasma by gas chromatography- quadrupole mass spectrometry and its application to a human pharmacokinetic study. AB - A specific and sensitive gas chromatography-mass spectrometry (GC-MS) with quadrupole mass analyzer type was developed and validated for the quantitative analysis of mequitazine in human plasma. After liquid-liquid extraction of plasma samples containing mequitazine and promethazine (internal standard, IS) using hexane with pH adjustment, the extract was evaporated and an aliquot of reconstituted residue was injected into the GC-MS system. The assay showed linearity over a concentration range from 1 to 50 ng/mL. Intra- and inter-day precision for mequitazine was <9.09 and 9.29%, respectively, and intra- and inter day accuracy ranged from -7.97 to 9.05% and from -1.51 to 7.89%, respectively. The lower limit of quantification was 1 ng/mL in the present assay. The developed analytical method was successfully applied to a pharmacokinetic study after a single oral administration of mequitazine in human subjects. PMID- 26268747 TI - [Comments on "ITMIG consensus statement on the use or the WHO histological classification of thymoma and thymic carcinoma: refined definitions, histological criteria, and reporting"]. PMID- 26268748 TI - [Comments on "The American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification]. PMID- 26268746 TI - An insight into current concepts and techniques in resin bonding to high strength ceramics. AB - BACKGROUND: Reliable bonding between high strength ceramics and resin composite cement is difficult to achieve because of their chemical inertness and lack of silica content. The aim of this review was to assess the current literature describing methods for resin bonding to ceramics with high flexural strength such as glass-infiltrated alumina and zirconia, densely sintered alumina and yttria partially stabilized tetragonal zirconia polycrystalline ceramic (Y-TZP) with respect to bond strength and bond durability. METHODS: Suitable peer reviewed publications in the English language were identified through searches performed in PubMed, Google Search and handsearches. The keywords or phrases used were 'resin-ceramic bond', 'silane coupling agents', 'air particle abrasion', 'zirconia ceramic' and 'resin composite cements'. Studies from January 1989 to June 2015 were included. RESULTS: The literature demonstrated that there are multiple techniques available for surface treatments but bond strength testing under different investigations have produced conflicting results. CONCLUSIONS: Within the scope of this review, there is no evidence to support a universal technique of ceramic surface treatment for adhesive cementation. A combination of chemical and mechanical treatments might be the recommended solution. The hydrolytic stability of the resin ceramic bond should be enhanced. PMID- 26268749 TI - [ALK gene fusion associated non-small cell lung cancer: automated immunostainer detection and clinicopathologic perspectives]. AB - OBJECTIVE: To explore the automated immunostainer screening anaplastic lymphoma kinase (ALK) gene fusion non-small cell lung cancer (NSCLC) and clinicopathological characteristics of the molecular subtype lung cancers. Methods Five hundred and sixty-six cases of NSCLC were collected over a 16 month period. The test for ALK was performed by Ventana automated immunostainer with anti-ALK D5F3. The histological features, treatment and outcome of patients were assessed. Results Thirty-eight cases (6.7%, 38/566) of NSCLC showed ALK gene fusion. The frequency of ALK gene fusion was higher in male (7.1%, 25/350) than that in female (6.0%, 13/216) patients, but not achieving statistical significance (chi2 = 0.270, P = 0.604). ALK + NSCLC was more significantly more frequent in patients < or = 60 years (9.9%, 28/282) than >60 years (3.5% , 10/284) of age. Histologically, the ALK + NSCLCs were mostly adenocarcinoma (81.6%, 31/38) , among which eighteen cases were solid predominant subtype with mucin production; nine cases were acinar predominant subtype; one case was papillary predominant subtype and three cases were invasive mucinous adenocarcinoma. The ALK + non-adenocarcinoma included three cases of squamous cell carcinoma, three cases of adenosquamous carcinoma and one case of pleomorphic carcinoma. Among the ALK + NSCLC patients, the number of non/light cigarette smokers (86. 8% , 33/38) was more than that of heavy smokers. Twenty nine cases were stages III and IV; twenty-nine cases showed lymph node metastasis; twenty cases showed metastases mostly to brain and bone; and one case showed EGFR gene mutation coexisting with ALK gene fusion. Twelve of fifteen patients received crizotinib therapy and remained stable. Conclusions NSCLC with ALK gene rearrangement shows distinctive clinical and histological features. Ventana-IHC may he a feasible and valid technique for detection of ALK rearrangement in NSCLC. PMID- 26268750 TI - [Relationship between histopathologic characteristics and epidermal growth factor receptor mutation in lung adenocarcinoma]. AB - OBJECTIVE: To correlate morphological features with mutations of epidermal growth factor receptor (EGFR) in lung adenocarcinomas. METHODS: According to 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Lung Adenocarcinoma Classification, a total of 72 surgically resected lung adenocarcinomas were collected and classified into different histological subtypes and different cell types (hobnail, columnar and polygonal). EGFR gene mutation was detected with the amplification refractory mutation method provided by the EGFR mutation test kit. The correlation between these subtypes and EGFR mutations were evaluated. RESULTS: Mutations of EGFR were detected in 48.6% (35/72) of lung adenocarcinomas; 19del and L858R were major mutational types (88.6%, 31/35). EGFR mutations were associated with female gender, non-smoking status, and well to moderately differentiated tumor histology. EGFR mutation types were not associated with age, smoking index, lymph node metastasis, stage, status of whether have or not have inclusion bodies or psammoma bodies and mitotic level. Correlations were observed between acinar and papillary adenocarcinoma subtypes and EGFR mutations according to the new classification. EGFR mutation was rare in the subtype of solid adenocarcinoma with mucin production and almost never observed in special subtypes (mainly mucinous and colloid adenocarcinoma). In addition, EGFR mutation was associated with the hobnail cell type. CONCLUSION: Lung adenocarcinomas of predominate acinar and papillary histological subtypes with hobnail cell morphology are good predictors for EGFR mutations. PMID- 26268751 TI - [Immunohistochemical evaluation of mutant p53 protein over-expression in non mucinous adenocarcinoma in-situ and invasive adenocarcinoma, NOS of lung]. AB - OBJECTIVE: To study the over-expression of mutant p53 protein in non-mucinous adenocarcinoma in-situ (NMAIS) and invasive adenocarcinoma, NOS of lung. METHODS: Immunohistochemical study for p53 protein was performed on 17 cases of NMAIS and 70 cases of invasive adenocarcinoma, NOS of lung. The difference in p53 over expression between the two tumor subtypes was analyzed. RESULTS: The over expression of mutant p53 protein was observed in 0 case (0%) of NMAIS and 37 cases (52.9%) of invasive adenocarcinoma, NOS of lung. The difference was of statistical significance (P = 0.000). CONCLUSION: Mutant p53 protein over expression may play a role in the progression of NMAIS to invasive adenocarcinoma, NOS. PMID- 26268752 TI - [Tumors with poroid features: a clinicopathologic analysis of 45 cases]. AB - OBJECTIVE: To investigate the clinicopathological features and the differential diagnosis of poroma and porocarcinoma. METHODS: Histopathological characteristics and clinical data of 35 cases of poroma and 10 cases of porocarcinoma were analyzed retrospectively. RESULTS: The average age of 35 patients of poroma was 48 years. The average age of 10 patients of porocarcinoma was 65 years. Both poroma and porocarcinoma occured most frequently on the scalp and face,as well as the extremities. Histologically, cases of poroma were divided into three subtypes, including classic poroma (23 cases), hidroacanthoma simplex (3 cases) and dermal duct tumor (9 cases). Residual foci of benign poroma were found in all cases of porocarcinoma, most of which were classic poroma. The malignant components showed severe dysplasia and/or stromal infiltration. CONCLUSION: The diagnosis of poroma and porocarcinoma is mainly based on the microscopic characteristics. An invasive architectural pattern and/or significant cytologic pleomorphism are the most important clues for the diagnosis of porocarcinoma. Neither focal mitotic activity nor the presence of necrosis was the diagnostic feature of porocarcinoma. Malignant transformation can occur in some cases of long existing poroma with recent, rapid tumor enlargement. PMID- 26268753 TI - [Expression of microRNA-10a-5p in laryngeal epithelial premalignant lesions]. AB - OBJECTIVE: To investigate the expression of microRNA-10a-5p (miR-10a) in laryngeal epithelial premalignant lesions (LEPL) and to analyze the correlations of its dysregulation with clinicopathologic parameters of LEPL. METHODS: According to the WHO classification (2005), 94 cases of LEPL were grouped into mild dysplasia (MID), moderate dysplasia (MOD), severe dysplasia (SD) and carcinoma in situ ( CIS). The expression of miR-10a in 94 cases of LEPL was detected by quantitative real-time polymerase chain reaction (qRT-PCR), and correlated with the clinical and follow-up data of all LEPL patients. RESULTS: miR-10a was down-regulated in LEPL with increasing grade of dysplasia. There was significantly statistical difference between low-risk ( MID + MOD) and high-risk ( SD + CIS) lesion groups (P = 0.03). The linear regression analysis showed that miR-10a was correlated with grade and gender of LEPL (P < 0.05). CONCLUSIONS: Down regulation of miR-10a may be a useful molecular marker for grading of LEPL and diagnosis of early laryngeal cancer. PMID- 26268754 TI - [Expression of EpCAM and E-cadherin in papillary thyroid carcinoma and its clinicopathologic significance]. AB - OBJECTIVE: To study the expression of EpCAM and E-cadherin in papillary thyroid carcinoma and to analyze its correlation with various clinicopathologic parameters. METHODS: Immunohistochemical study for EpCAM and E-cadherin was carried out in 91 cases of papillary thyroid carcinoma. Twenty-four cases of papillary hyperplasia of thyroid were used as controls. RESULTS: In all of the 24 cases of papillary hyperplasia, EpCAM was located on the cell membrane, while in the 91 cases of papillary thyroid carcinoma studied, EpCAM was located within the cytoplasm, with 36.3% (33/91) showing nuclear localization as well. In all the papillary hyperplasia cases studied, E-cadherin showed membranous expression. E cadherin expression was reduced in 84.6% (77/91) of papillary thyroid carcinoma, as compared with the surrounding native thyroid parenchyma. Amongst the 33 cases of papillary thyroid carcinoma which showed nuclear localization of EpCAM, 30 cases also showed reduced E-cadherin expression. There was a positive correlation between nuclear expression of EpCAM and loss of E-cadherin expression (P = 0.000; Spearman correlation coefficient = 0.857). Nuclear expression of EpCAM correlated with follicular variant of papillary thyroid carcinoma and presence of extrathyroidal extension ( P = 0.037 and 0.033, respectively). Loss of E-cadherin expression correlated with age of patients and presence of lymph node metastasis (P = 0.018 and 0.010, respectively). CONCLUSIONS: E-cadherin expression is reduced in papillary thyroid carcinoma, as compared with native thyroid parenchyma and papillary hyperplasia. Papillary thyroid carcinoma shows loss of EpCAM membranous expression and increased cytoplasmic/nuclear accumulation. Detection of these two markers may provide a valuable reference in defining the biologic behaviors of papillary thyroid carcinoma, including extrathyroidal extension and lymph node metastasis. PMID- 26268755 TI - [Surgical pathology of revision after knee and hip arthroplasty]. AB - OBJECTIVE: To investigate clinical characteristics and pathological changes of tissue surrounding prosthesis after hip and knee arthroplasty. METHODS: A total of 67 patients receiving hip and knee arthroplasty were included in the study and pathological changes of the revision specimens were evaluated by microscopic examination. RESULTS: Of 67 patients, there were 25 males and 42 females (ratio of 0.6) with a mean age of 64 years. There were 42 cases of revision hip prosthesis and 25 cases of knee prosthesis. The primary causes for the revision varied, including 20 cases of infection (29.9%, within 3 months in 9 cases,3 to 24 months in 3 cases and over 24 months in 8 cases), 14 cases of pain (20.9%), 13 cases of loosening of the prosthesis (19:4%), 9 cases of joint stiffness (13.4%), 8 cases of prosthetic dislocation (11.9%), and 3 cases of prosthesis fracture (4.5%). Pathological findings in the tissue surrounding the prostheses included debris reaction, histiocytes, acute inflammatory, chronic non-specific inflammation, pigmented villonodular synovitis (PVNS), "pseudomembranous", calcification, necrosis, sequestrum, etc. These histological changes were frequently admixed. CONCLUSIONS: Various reasons may lead to hip and knee revision arthroplasty. The main pathological findings include infection, debris granulomas, chronic non-specific inflammatory changes, PVNS. The surgical pathology of the prosthesis provids guidances for clinical treatment and basic research. PMID- 26268756 TI - [Pathology of effects of dust storm on rat lung tissue]. PMID- 26268757 TI - [Ovarian immature teratoma with gliomatosis peritonei: a clinicopathologic study]. PMID- 26268758 TI - [Correlation between dissemination growth pattern in invasive front and risk of lymph node metastasis in papillary thyroid carcinoma]. PMID- 26268759 TI - [Pituicytoma: a study of 3 cases with literature review]. PMID- 26268760 TI - [Cytochrome oxidase and succinate dehydrogenase double staining method in mitochondrial myopathy]. PMID- 26268761 TI - [Pulmonary lymphangioleiomyomatosis with renal angiomyolipoma: report of a case]. PMID- 26268762 TI - [Giant solitary fibrous tumor of the heart: report of a case]. PMID- 26268763 TI - [Ovarian stromal tumor with minor sex cord elements and coexistent endometrial carcinoma: report of a case]. PMID- 26268764 TI - [Pathologic assessment and clinical impacts for endometrial cancer and precursors after progestin treatment]. PMID- 26268765 TI - [Research progress of feature and function of mucins in breast cancer]. PMID- 26268766 TI - Multiwall Carbon Nanotube-Induced DNA Damage and Cytotoxicity in Male Human Peripheral Blood Lymphocytes. AB - Carbon nanotubes (CNTs) have been introduced recently as a novel carrier system for both small and large therapeutic molecules. Biotin-functionalized single-wall CNTs have been conjugated with the anticancer agent taxoid using a cleavable linker, and multiwall carbon nanotubes (MWCNTs) conjugated with iron nanoparticles have been efficiently loaded with doxorubicin. The MWCNTs are effective transporters for biological macromolecules and drugs to target cells and tissues, thereby attracting the attention of the biomedical industry. Administrating MWCNTs for medical application invariably involves intravenous administration and ultimate contact with human peripheral blood lymphocytes (HPBLs), yet toxicological studies on the effect of MWCNTs on HPBLs are lacking. Accordingly, this study evaluated the cytotoxic and genotoxic effects of MWCNTs on healthy male HPBLs. Healthy male HPBLs were treated with MWCNTs at 3 different concentrations (12.5, 25, and 50 MUg/mL) for 48 hours. Under these conditions, the MWCNTs induced significant cell growth retardation, DNA damage, and cytotoxicity. The MWCNT-treated HPBLs also exhibited an increased intracellular reactive oxygen species level during the experimental period, which leads to cell damage and death, proliferation inhibition, DNA damage, and an inflammatory response. PMID- 26268767 TI - Acute Phase Responses to Novel, Investigational Vaccines in Toxicology Studies: The Relationship Between C-Reactive Protein and Other Acute Phase Proteins. AB - The objective of this study was to determine the effects of investigational vaccine candidates on acute-phase proteins (APPs) as determined in GLP toxicology studies. Sixty-four GLP toxicity studies, which were submitted to the Food and Drug Administration from 2008 to 2012 in support of proposed clinical investigations, were reviewed and entered into a database. These studies employed the intramuscular route of injection and were conducted using New Zealand White rabbits. A retrospective review of these GLP toxicity studies was conducted to evaluate the changes in plasma levels of C-reactive protein (CRP), fibrinogen, and albumin as APPs following the administration of various investigational vaccines. The incidence and intensity of responses associated with acute-phase responses both positive and negative were observed to increase in animals when treated with vaccines containing more potent immunological components such as novel adjuvants that activate Toll-like receptors in the investigational vaccine products. Changes in plasma levels of CRP were prominent among these responses and provided a basis to propose a classification scheme of H, M, L, and N responding groups. These changes in plasma proteins reflect an activation of the acute-phase response and indicate increasing levels of systemic inflammation, which potentially may be correlated with important clinical adverse events. PMID- 26268768 TI - Mixture Effects of 3 Mechanistically Different Steroidogenic Disruptors (Prochloraz, Genistein, and Ketoconazole) in the H295R Cell Assay. AB - Mixture effects of 3 model endocrine disruptors, prochloraz, ketoconazole, and genistein, on steroidogenesis were tested in the adrenocortical H295R cell line. Seven key steroid hormones (pregnenolone, progesterone, dehydroepiandrosterone, androstenedione, testosterone, estrone, and 17beta-estradiol) were analyzed using gas chromatography and tandem mass spectrometry (GC-MS/MS) to investigate the effects throughout the steroidogenic pathway. Current modeling approaches often rely on models assuming compounds acting independently and that the individual effects in some way can be summarized to predict a mixture effect. In H295R cells with an intact steroidogenic pathway, such assumptions may not be feasible. The purpose of this study was therefore to evaluate whether effects of a mixture with differing modes of action followed or deviated from additivity (concentration addition) and whether the H295R cell line was suitable for evaluating mixture toxicity of endocrine disruptors with different modes of action. The compounds were chosen because they interfere with steroidogenesis in different ways. They all individually decrease the concentrations of the main sex steroids downstream but exert different effects upstream in the steroidogenic pathway. Throughout the study, we observed lowest observed effect concentrations of mixtures at levels 2 to 10 times higher than the predicted EC(50), strongly indicating antagonistic effects. The results demonstrate that chemical analysis combined with the H295R cell assay is a useful tool also for studying how mixtures of endocrine disruptors with differing modes of action interfere with the steroidogenic pathway and that existing models like concentration addition are insufficient in such cases. Furthermore, for end points where compounds exert opposite effects, no relevant models are available. PMID- 26268769 TI - Determination of CYP3A4 Inducing Properties of Compounds Using a Laboratory Developed Cell-Based Assay. AB - A cell-based assay to measure cytochrome P450 3A4 (CYP3A4) induction was developed to screen for potential CYP3A4 inducers. This 96-well format assay utilizes HepG2 cells transfected with a gene construct of CYP3A4 proximal promoter linked to green fluorescence protein (GFP) gene, and the expression of the GFP is then measured quantitatively. Bergamottin at 5 to 25 umol/L produced low induction relative to the positive control. Both curcumin and lycopene were not found to affect the expression of GFP, suggesting no induction properties toward CYP3A4. Interestingly, resveratrol produced significant induction from 25 umol/L onward, which was similar to omeprazole and may warrant further studies. In conclusion, the present study demonstrated that this cell-based assay can be used as a tool to evaluate the potential CYP3A4 induction properties of compounds. However, molecular docking data have not provided satisfactory pointers to differentiate between CYP3A4 inducers from noninducers or from inhibitors, more comprehensive molecular screening may be indicated. PMID- 26268770 TI - Epigenetic Regulation in Environmental Chemical Carcinogenesis and its Applicability in Human Health Risk Assessment. AB - Although several studies have shown that chemically mediated epigenetic changes are an etiological factor in several human disease conditions, the utility of epigenetic data, such as DNA methylation, in the current human health risk assessment paradigm is unclear. The objective of this study is to investigate the relationship between the points of departure (PODs) for cancer incidence and DNA methylation changes in laboratory animals exposed to the following environmental toxicants: bromodichloromethane, dibromochloromethane, chloroform, hydrazine, trichloroethylene, benzidine, trichloroacetic acid, and di(2-ethylhexyl) phthalate (DEHP; a known reproductive toxicant). The results demonstrate that the PODs for cancer incidence and altered DNA methylation are similar. Furthermore, based on the available data, the POD for DNA methylation appeared more sensitive compared to that for cancer incidence following the administration of DEHP to rats during different life stages. The high degree of correlation between PODs for cancer incidence and DNA methylation (for both total DNA and individual genes) suggests that DNA methylation end points could potentially be used as a screening tool in predicting the potential toxicity/carcinogenicity and in prioritizing large numbers of chemicals with sparse toxicity databases. The life stage during which treatment occurs is also an important consideration when assessing the potential application of epigenetic end points as a screening tool. PMID- 26268771 TI - Quality audits of radiotherapy centres in Latin America: a pilot experience of the International Atomic Energy Agency. AB - BACKGROUND: In Latin America radiotherapy quality varies significantly among hospitals, where highly equipped academic centers coexist with others not meeting minimal requirements. In 2007, the International Atomic Energy Agency published guidelines for auditing radiotherapy centers, known as the "Quality Assurance Team for Radiation Oncology" (QUATRO) audits. The present report summarizes a pilot experience with QUATRO audits to 12 radiotherapy centres. METHODS: The findings from QUATRO audits conducted in 12 radiotherapy centres in Latin America between 2008 and 2013 were analysed. Events representing weaknesses or gaps in the process of radiotherapy were recorded. Relevant data for estimating human and technological needs of visited centres were processed. The main difficulties and strengths faced by institutions were also documented. RESULTS: All 12 radiotherapy centres were successfully audited following the QUATRO method. IAEA provided a dosimetry kit for quality control. Forty percent of audited institutions were immersed in a health system that did not recognize cancer as a public health priority problem. With few exceptions, local training programs for physicists and technologists were scarce and research was not an activity of interest among physicians. Centres were provided with sufficient staff to meet the local demand, both in the case of radiation oncologists, physicists and radiation therapists. Three centres lacking the minimum infrastructure were identified. Three institutions did not perform gynaecological brachytherapy, and one installation delivered around 900 teletherapy treatments annually without simulation, planning or dosimetry equipment for that purpose. Recommendations to centres were classified as related to personnel, infrastructure, processes and institutional organizational aspects. Many recommendations warned governments about the evident need for allocating more budgetary resources to radiotherapy. Most recommendations pointed out different aspects related to strengthen human resources training and technological support to the audited centres. Scheduled follow-up visits were also stressed. CONCLUSION: The QUATRO audits proved to be a valuable tool for identifying weaknesses in infrastructure, human resources and procedures in radiotherapy centres. Follow-up visits conducted by the IAEA or by regional or local organizations are necessary in order to evaluate outcomes and sustainability of implemented recommendations. PMID- 26268772 TI - A prospective randomized clinical trial into the capacity of a toothpaste containing NovaMin to prevent white spot lesions and gingivitis during orthodontic treatment. AB - BACKGROUND: White spot lesions and gingivitis represent common, yet challenging, dilemmas for orthodontists. Fluoride has shown some benefit as a protective measure against demineralization; however, this is usually insufficient for orthodontic patients with less than ideal oral hygiene. Dentifrices containing calcium sodium phosphosilicate bioactive glass (NovaMin) have been proposed to aid in prevention of white spot lesions and gingival inflammation. Thus, the purpose of this study was to determine if the use of NovaMin reduces the formation of white spot lesions and improves gingival health in orthodontic patients. METHODS: This was a prospective, double-blind, randomized controlled trial. Forty-eight patients undergoing orthodontic treatment were randomly allocated to two groups. The control group consisted of 24 patients who received over-the-counter fluoride toothpaste (Crest(r)), while the study group consisted of 24 patients who were given the test dentifrice (ReNewTM) containing 5 % NovaMin and fluoride. Patients were followed up for 6 months on a monthly basis. Decalcification, gingival health, plaque, and bacteria levels were evaluated every 3 months. Statistical analysis was performed using both parametric and non parametric tests to identify differences between groups at different time points. RESULTS: There were no significant differences between the groups in regard to changes in white spot lesions, plaque, or gingival health (P > 0.05). There was a trend toward improvement in white spot lesions found in subjects using Crest(r) at the 3-month time point; however, this was not sustained throughout the study. CONCLUSIONS: Our results indicate that a toothpaste containing NovaMin does not differ significantly compared to traditional fluoride toothpaste for improving white spot lesions and gingivitis in orthodontic patients. PMID- 26268773 TI - Conditional self-discrimination enhances dendritic spine number and dendritic length at prefrontal cortex and hippocampal neurons of rats. AB - We studied conditional self-discrimination (CSD) in rats and compared the neuronal cytoarchitecture of untrained animals and rats that were trained in self discrimination. For this purpose, we used thirty 10-week-old male rats were randomized into three groups: one control group and two conditioning groups: a comparison group (associative learning) and an experimental group (self discrimination). At the end of the conditioning process, the experimental group managed to discriminate their own state of thirst. After the conditioning process, dendritic morphological changes in the pyramidal neurons of the prefrontal cortex and CA1 region of the dorsal hippocampus were evaluated using Golgi-Cox stain method and then analyzed by the Sholl method. Differences were found in total dendritic length and spine density. Animals trained in self discrimination showed an increase in the dendritic length and the number of dendritic spines of neurons of the prefrontal cortex and CA1 region of the dorsal hippocampus. Our data suggest that conditional self-discrimination improves the connectivity of the prefrontal cortex and dorsal CA1, which has implications for memory and learning processes. PMID- 26268774 TI - The importance of psychosexual counselling in the re-establishment of organic and erotic functions after penile prosthesis implantation. AB - Although many studies about penile prosthesis implantation (PPI) have been published so far, only a small amount of them take into account patients and partners outcome in terms of satisfaction and erotic function. The aim of this study is to explore the value of psycosexual counselling in and the sexual and erotic function of penile prosthesis recipients. Thirty patients and their partners were randomised into two groups. In arm A (case group) patients and their partners underwent a multistep psychosexual counselling before and after surgery. In arm B (control group) surgery was performed without the specific psychosexual counselling scheme. Specific questionnaires (International Index of Erectile Function (IIEF) and the Sexual Daydreaming Scale (SDS)) were administered before surgery and 12 months afterwards. Twenty-four months postoperatively patients were asked to complete the Global Assessment Questions (GAQ) and the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), while their partners were asked to answer to the EDITS partner's section. Between January 2009 and October 2011, we enrolled 30 patients undergoing PPI in our institution (15 in each arm). Twenty-four months postoperative follow-up is available for all of them. No significant differences between the two groups in terms of baseline questionnaires scores were observed. Mean IIEF score was significantly higher in case group (arm A 68.3, arm B 53.4, P-value<0.001). At 12 months after PPI the improvement of erotic function according to SDS was significantly higher in the study group for both patients and their partners. Improvement in satisfaction rates were confirmed at 24 months, with statistically significant scores for EDITS in arm A patients and partners as compared with arm B. PPI with a pre- and postoperative psychosexual counselling scheme resulted in better postoperative sexual activity and erotic function for both patients and partners than PPI alone. PMID- 26268775 TI - Elevated Serum Level of Angiopoietin-2 as a Potential Marker for Poor Prognosis in Small Cell Lung Cancer. AB - Small cell lung cancer (SCLC) is a fast-growing cancer with poor prognosis. Patients with extensive-stage SCLC are generally treated with chemotherapy. Thus, it is essential to identify a predictor of efficacy and prognosis for SCLC. Angiopoietin-2 promotes vascular remodeling and angiogenesis. Increasing evidence reveals that angiopoietin-2 is preferentially expressed in cancer cells, and elevated angiopoietin-2 expression is related to invasive and metastatic phenotypes in various cancers. However, serum angiopoietin-2 level and its prognostic potential in SCLC have not been investigated. The aim of this study was to determine the usefulness of angiopoietin-2 level as a predictor of efficacy and prognosis for SCLC. This study consisted of sixty patients with SCLC. Each patient received four cycles of cisplatin-etoposide chemotherapy, and was followed for 36 months. Serum angiopoietin-2 levels were measured by Enzyme linked immunosorbent assays. The angiopoietin-2 levels were significantly higher in SCLC patients than those in healthy subjects (P < 0.001). The patients were divided into high-level group (32 patients, 2,923.9 +/- 294.7 pg/ml) and low level group (28 patients, 1,789.5 +/- 355.1 pg/ml) according to the mean value of the angiopoietin-2 level (2,400 pg/ml). Compared with the patients in the high level group, the patients in the low-level group showed remarkably survival advantage (P = 0.002). During chemotherapy, the patients in the low-level group showed better treatment response than the patients in the high-level group (P < 0.05). Therefore, angiopoietin-2 might be useful as a prognostic factor for SCLC and for predicting SCLC response to chemotherapy. PMID- 26268776 TI - Expression of Fibroblast Growth Factor 10 Is Correlated with Poor Prognosis in Gastric Adenocarcinoma. AB - Fibroblast growth factor receptor 2 (FGFR2) has been proved to be a significant prognostic factor and a potential therapeutic target in several types of cancer, including gastric cancer. FGFR2 consists two isoforms: FGFR2-IIIb and FGFR2-IIIc, which can be stimulated by different ligands and trigger different downstream signaling pathways. As a specific ligand to FGFR2-IIIb, fibroblast growth factor 10 (FGF10) is expressed in the gastric mesenchyme cell and is involved in stomach development and morphogenesis, but its expression and clinical significance is not well elucidated in gastric cancer. We analyzed FGF10 expression by immunohistochemistry in 178 samples of gastric adenocarcinoma (134 male and 44 female patients, with the average age of 63.2 years old and the average follow-up of 21.6 months). Using the arbitrarily scoring method based on positive cell percentage and staining intensity, we sub-divided the patients into FGF10 high expression group (58 patients) and low-expression group (120 patients). We thus found that FGF10 expression is significantly associated with lymph node invasion (P = 0.004) and distant metastasis (P = 0.032). Importantly, FGF10 expression is an independent unfavorable prognostic factor (P = 0.042). Moreover, FGF10 knockdown significantly decreased the migration of cultured gastric adenocarcinoma cells, suggesting that FGF10 could promote the invasion of gastric adenocarcinoma. In conclusion, FGF10 expression was identified as a poor prognostic biomarker in gastric adenocarcinoma, and FGF10 could promote the invasion of gastric cancer cells. We suggest that FGF10 could be a potential and promising drug target in gastric adenocarcinoma. PMID- 26268778 TI - Revisiting global body politics in Nepal: A reflexive analysis. AB - Using the example of a human rights training in Nepal, the author looks at global body politics in a reflexive piece on her engagement in development practices that translate western feminist ideas on gender inequality and empowerment via UN human rights policies into non-western contexts. It firsts look at postcolonial and critical literature on feminist engagement in gender and development processes including a discussion on the concept of global body politics before examining briefly the framing of gender-based violence in Nepal. The core of the paper is a reflexive analysis and interrogation of the training in Nepal in order to bring out the tensions and contradictions around western developmental, feminist and human rights discourses. The discussion looks at how difficult it is for feminist, human rights and developmental discourses and practices to unmoor themselves from the notion of the 'expert' and those who do the rights/work/righting rights training and those who are perennially seen as requiring training. The conclusion reflects on possibilities of other epistemic practices found in intercultural dialogues. PMID- 26268777 TI - The Salmonella effector protein SifA plays a dual role in virulence. AB - The virulence of Salmonella relies on the expression of effector proteins that the bacterium injects inside infected cells. Salmonella enters eukaryotic cells and resides in a vacuolar compartment on which a number of effector proteins such as SifA are found. SifA plays an essential role in Salmonella virulence. It is made of two distinct domains. The N-terminal domain of SifA interacts with the host protein SKIP. This interaction regulates vacuolar membrane dynamics. The C terminal has a fold similar to other bacterial effector domains having a guanine nucleotide exchange factor activity. Although SifA interacts with RhoA, it does not stimulate the dissociation of GDP and the activation of this GTPase. Hence it remains unknown whether the C-terminal domain contributes to the function of SifA in virulence. We used a model of SKIP knockout mice to show that this protein mediates the host susceptibility to salmonellosis and to establish that SifA also contributes to Salmonella virulence independently of its interaction with SKIP. We establish that the C-terminal domain of SifA mediates this SKIP-independent contribution. Moreover, we show that the two domains of SifA are functionally linked and participate to the same signalling cascade that supports Salmonella virulence. PMID- 26268779 TI - Benign melanocytic lymph node deposits in the setting of giant congenital melanocytic nevi: the large congenital nodal nevus. AB - BACKGROUND: Benign melanocytic rests are a frequent finding in superficial lymph nodes removed during sentinel lymph node biopsies for melanoma. Whereas the histopathology of these deposits is well understood, very little is known regarding melanocytic lymph node deposits in the setting of giant congenital melanocytic nevi. METHODS: We analyzed lymph nodes removed from the drainage basin of giant congenital melanocytic nevi in three patients who had developed melanoma within their giant congenital nevi. RESULTS: Two of three patients showed widespread, capsular and parenchymal melanocytic deposits in multiple nodes (9 of 11 nodes in one patient and 6 of 8 in the other). Melanocytes were small, non-mitotically active and resembled those in the associated giant congenital melanocytic nevus. Melanocytes were arranged singly and in small nests ~0.05 mm in diameter, with some larger sheets up to 1 mm. Nodal melanocytes stained for Melan A and S100 on immunohistochemical evaluation, but showed negative or minimal HMB-45 reactivity. CONCLUSIONS: Evaluation of lymph nodes in the setting of giant congenital melanocytic nevi is complicated by the presence of often numerous, parenchymal melanocytic nevic deposits. Bland cytology and minimal or absent HMB-45 staining may be helpful in differentiating these nodal melanocytic nevi from metastatic melanoma. We term this phenomena large congenital nodal nevus. PMID- 26268780 TI - Body mass index: short- and long-term impact on kidney transplantation. AB - AIM: The topic of pretransplantation body mass index (BMI) is still a matter of controversy. The aim of this study was to investigate the influence of pretransplant BMI on short- and long-term outcomes in patients receiving kidney transplant. METHODS: We have analysed 521 renal transplant recipients (RTRs). BMI was categorised as follows: less than or equal to 20, more than 20 to less than or equal to 25, more than 25 to less than or equal to 30 and more than 30 RESULTS: The distribution of the RTRs per category of BMI at baseline was: <= 20 (14.4%), > 20 to <= 25 (50.9%), > 25 <= 30 (26.9%) and > 30 (7.9%). In further analysis, the patients were stratified into four groups according to their pretransplant BMI values. There was no difference in the rates of delayed graft function between the four analysed groups of patients. Recipients with normal pre transplant BMI were less likely to develop wound complications in comparison to the recipients with high BMI (p = 0.04) and obese recipients (p = 0.0001). RTRs with normal BMI were less likely to develop lymphoceles in comparison to the recipients with high BMI (p = 0.0003). Obese patients were more likely to develop lymphocele in comparison to the recipients with high BMI (p = 0.01). Obese recipients had a longer mean length of hospital stay in comparison to the recipients with normal BMI (p = 0.04). There was no significant difference regarding 1-year graft and patient survival, as well as because of acute rejection crisis between the investigated groups of recipients. We did not find any significant difference in 5-year patients and graft survival between those RTRs with BMI > 20 to <= 25 and to those recipients with BMI > 25. CONCLUSION: Overweight and obese transplant candidates should not be excluded from kidney transplantation. PMID- 26268781 TI - Perceived barriers and benefits to physical activity in colorectal cancer patients. AB - PURPOSE: There is emerging evidence for the benefits of physical activity (PA) post-diagnosis for colorectal cancer (CRC) survivors. However, population studies suggest activity levels in these patients are very low. Understanding perceived barriers and benefits to activity is a crucial step in designing effective interventions. METHODS: Patients who were between 6 months and 5 years post diagnosis with non-metastasised disease were identified from five London (UK) hospitals. Four hundred and ninety five completed a lifestyle survey that included open-ended questions on their perceived barriers (what things would stop you from doing more physical activity?) and benefits (what do you think you would gain from doing more physical activity?). Patients also recorded their activity levels using the Godin Leisure Time Exercise Questionnaire, along with sociodemographic and treatment variables. RESULTS: The most commonly reported barriers related to cancer and its treatments (e.g. fatigue). Age and mobility related comorbidities (e.g. impaired mobility) were also frequently cited. Those who reported age and mobility as barriers, or reported any barrier, were significantly less active even after adjustment for multiple confounders. The most frequently reported benefits were physiological (e.g. improving health and fitness). Cancer-related benefits (such as prevention of recurrence) were rarely reported. Those perceiving physiological benefits or perceiving any benefits were more active in unadjusted models, but associations were not significant in adjusted models. CONCLUSIONS: We have identified important barriers and facilitators in CRC survivors that will aid in the design of theory-based PA interventions. PMID- 26268782 TI - Sixty-minute infusion rituximab protocol allows for safe and efficient workflow. AB - PURPOSE: Rituximab is a chimeric monoclonal antibody approved to treat B cell non Hodgkin's lymphoma (NHL). Infusion reactions among NHL patients are common during the first exposure but decrease with subsequent infusions. We sought to assess the safety and feasibility of a rituximab rapid infusion protocol in the outpatient treatment area of a comprehensive cancer center. PATIENTS AND METHODS: Patients with indolent and intermediate B cell NHL were invited to enroll in this prospective, single-institution study if they had received the first dose of rituximab according to the manufacturer-labeled standard titration schedule without grade >2 infusion reaction. The subsequent infusion proceeded without the use of steroid premedication at 100 mg/h administered over 15 min, with the remaining dose given over 45 min. Time savings between rapid infusion and standard titration were calculated. RESULTS: Fifty patients received 60-min rituximab infusions during the second drug administration. No infusion-related reactions of any grade were observed with the rapid infusion protocol (0%, one sided 97.5% CI 0-7.1%). The mean time for the rapid rituximab infusion was 62.4 min (95% CI 61.2-63.6). When compared to the standard second dose infusion recommendation, a mean time of 94.2 min (95% 90-98.4) was saved with rapid infusion. Nursing surveys demonstrated 100% satisfaction with the rapid infusion protocol. CONCLUSIONS: Subsequent rituximab infusions can be safely administered over 60 min and without steroid premedication in an experienced outpatient infusion center when patients are appropriately screened. The faster infusions can reduce resource utilization and increase nursing satisfaction. TRIAL REGISTRATION: NCT01206777. PMID- 26268783 TI - Safety and tolerability of Kinesio Taping in patients with arm lymphedema: medical device clinical study. AB - PURPOSE: The aim of this study is to assess the safety and tolerability of Kinesio Taping (KT) in patients with arm lymphedema. METHOD: Medical device clinical study in women with arm lymphedema. Kinesio Tex Gold bandage was applied by the KT technique. Assessments and interviews were carried out both at the beginning and 4 days after intervention. Skin disorders, reported tolerance and modification of limb volume and function after intervention were assessed. Changes in limb volume and functionality before and after intervention were compared by the Student's t test and the Wilcoxon Signed-Rank test, considering significant p value <0.05. RESULTS: Twenty-four women were studied. After intervention, no patient had cutaneous lesions, vesicle or limb hyperthermia, and 4.2% presented skin peeling and redness. Most patients reported no change in social life and that they felt safer in the daily activity and were very pleased with the treatment. The patients presented improvement of upper limb functionality after intervention (p < 0.001). No difference of limb volume was found after intervention (p = 0.639). CONCLUSIONS: Kinesio Tex Gold bandage by the KT technique proved to be safe and tolerable in patients with lymphedema, with improved functionality and no change of the affected limb volume. PMID- 26268784 TI - How to improve the prevention of chemotherapy-induced nausea and vomiting? The French NAVI study. AB - PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) still remain frequent. The procedure for announcing the diagnosis (PAD) was an emblematic measure of the first French Plan Cancer aiming at providing patients with time to listen, information after cancer diagnosis, and discussion on treatments and their side effects. We aimed at assessing the risk factors of CINV, focusing on patients' satisfaction with the PAD. METHODS: This prospective multicentre study assessed the frequency and intensity of CINV among chemonaive patients during the first cycle of treatment. CINV was defined by >=1 emetic episode or reported nausea intensity >=3 on a 0-10 scale. Multivariate analysis was used to identify factors related to global CINV onset including satisfaction with the PAD (satisfaction score >=the median on a 0-10 scale). RESULTS: Data from 291 patients (women, 85.2%; mean age, 57 years) were analyzed. Most patients (69.4%) received highly emetogenic chemotherapy regimens and 77.7% received antiemetic drugs consistent with international guidelines. Acute, delayed and overall CINV were experienced by 40.4, 34.8 and 52.4% of patients, respectively. Sixty-seven per cent of patients were satisfied with the PAD. No relation was noted between PAD satisfaction and CINV onset. The nausea and vomiting dimension of the QLQ-C30 questionnaire before chemotherapy (OR 3.62), motion sickness history (OR 2.73), highly emetogenic CT (OR 2.73), anxiety (OR 1.99) and younger age (OR 1.96) were independent predictive factors. CONCLUSIONS: Although patients were mostly satisfied with the PAD, half of them experienced CINV. A state of anxiety could be identified during the PAD to be managed. PMID- 26268785 TI - In-service documentation tools and statements on palliative sedation in Germany- do they meet the EAPC framework recommendations? A qualitative document analysis. AB - BACKGROUND: Numerous (inter-)national guidelines and frameworks have been developed to provide recommendations for the application of palliative sedation (PS). However, they are still not widely known, and large variations in PS clinical practice can be found. AIM: This study aims to collect and describe contents from documents used in clinical practice and to compare to what extent they match the European Association for Palliative Care (EAPC) framework recommendations. DESIGN AND METHODS: In a national survey on PS in Germany 2012, participants were asked to upload their in-service templates, assessment tools, specific protocols, and in-service statements for the application and documentation of PS. These documents are analyzed by using systematic structured content analysis. RESULTS: Three hundred seven content units of 52 provided documents were coded. The analyzed templates are very heterogeneous and also contain items not mentioned in the EAPC framework. Among 11 scales for the evaluation of sedation level, the Ramsey Sedation Score (n = 5) and the Richmond Agitation-Sedation-Scale (n = 2) were found most often. For symptom assessment, three different scales were provided one time respectively. In all six PS statements, the common core elements were possible indications for PS, instructions on dose titration, patient monitoring, and care. Wide congruency exists for physical and psychological indications. Most documents coincide on midazolam as a preferred drug and basic monitoring in regular intervals. Aspects such as pre-emptive discussion of the potential role of sedation, informational needs of relatives, and care for the medical professionals are mentioned rarely. CONCLUSIONS: The analyzed templates do neglect some points of the EAPC recommendations. However, they expand the ten-point scheme of the framework in some details. The findings may facilitate the development of standardized consensus documentation and monitoring draft as an operational statement. PMID- 26268786 TI - Analysis of cerebrospinal fluid protein concentrations of patients with cryptococcal meningitis treated with antifungal agents. AB - BACKGROUND: Many neurological diseases are accompanied by an increase in the cerebrospinal fluid (CSF) protein concentration, which indicates dysfunction of the blood-CSF/blood-brain barrier. However, the significance CSF protein concentration of patients with cryptococcal meningitis (CM) is not fully understood. The aim of the present was to determine whether CSF protein concentrations correlated with the responses of patients to treatment with antifungal drugs. METHODS: We conducted a retrospective study of the analytical data of 623 lumbar punctures of 46 patients with CM who were treated at West China Hospital. We divided the patients into groups with good or poor responses to antifungal treatment. We used a generalized linear mixed model (GLMM) to evaluate the significance of the differences between the two groups. RESULTS: The baseline CSF protein concentrations of the good antifungal response group (GR group) (median = 0.97 g/L) were higher compared with those of the poor antifungal response group (PR-group) (median = 0.72 g/L). Analysis using the GLMM indicated that the CSF protein concentration of the GR-group decreased at a rate of 1.8 mg/L per day after antifungal treatment started and was 2.1 mg/L higher compared with that of the PR-group. CONCLUSIONS: Compared with poor responders, we found that the baseline CSF protein concentrations of good responders were higher and decreased at faster rate after the initiation of antifungal treatment. PMID- 26268788 TI - Adjusting prednisone using blood eosinophils reduces exacerbations and improves asthma control in difficult patients with asthma. AB - Severe or therapy-resistant asthma represents a major problem, and despite advanced treatment, many patients require oral corticosteroids (OCS). We aimed to determine if patients with severe asthma and elevated peripheral blood eosinophils (PBE) could have treatment with OCS adjusted using an algorithm that controlled PBE (<0.2 * 10(9) /L). In 11 patients, the OCS dose was adjusted to suppress PBE, leading to a reduced exacerbation frequency and improvement in asthma symptoms with an overall lower OCS dose. PMID- 26268789 TI - Impact of smoke-free legislation on perinatal and infant mortality: a national quasi-experimental study. AB - Smoke-free legislation is associated with improved early-life outcomes; however its impact on perinatal survival is unclear. We linked individual-level data with death certificates for all registered singletons births in England (1995-2011). We used interrupted time series logistic regression analysis to study changes in key adverse perinatal events following the July 2007 national, comprehensive smoke-free legislation. We studied 52,163 stillbirths and 10,238,950 live-births. Smoke-free legislation was associated with an immediate 7.8% (95%CI 3.5-11.8; p < 0.001) reduction in stillbirth, a 3.9% (95%CI 2.6-5.1; p < 0.001) reduction in low birth weight, and a 7.6% (95%CI 3.4-11.7; p = 0.001) reduction in neonatal mortality. No significant impact on SIDS was observed. Using a counterfactual scenario, we estimated that in the first four years following smoke-free legislation, 991 stillbirths, 5,470 cases of low birth weight, and 430 neonatal deaths were prevented. In conclusion, smoke-free legislation in England was associated with clinically important reductions in severe adverse perinatal outcomes. PMID- 26268790 TI - Rhodium-catalyzed C-H activation of hydrazines leads to isoquinolones with tunable aggregation-induced emission properties. AB - Using an internally oxidizing directing group (DG) strategy, we report a Rh(III) catalyzed synthesis of isoquinolones via C-H activation/annulation of benzoylhydrazines and alkynes. Tunable double cascade cyclization of benzoylhydrazines with two equivalents of alkynes led to tetracyclic amides. These N-heterocycles demonstrated adjustable AIE properties. PMID- 26268791 TI - Extensive shift in placental transcriptome profile in preeclampsia and placental origin of adverse pregnancy outcomes. AB - One in five pregnant women suffer from gestational complications, prevalently driven by placental malfunction. Using RNASeq, we analyzed differential placental gene expression in cases of normal gestation, late-onset preeclampsia (LO-PE), gestational diabetes (GD) and pregnancies ending with the birth of small-for gestational-age (SGA) or large-for-gestational-age (LGA) newborns (n = 8/group). In all groups, the highest expression was detected for small noncoding RNAs and genes specifically implicated in placental function and hormonal regulation. The transcriptome of LO-PE placentas was clearly distinct, showing statistically significant (after FDR) expressional disturbances for hundreds of genes. Taqman RT-qPCR validation of 45 genes in an extended sample (n = 24/group) provided concordant results. A limited number of transcription factors including LRF, SP1 and AP2 were identified as possible drivers of these changes. Notable differences were detected in differential expression signatures of LO-PE subtypes defined by the presence or absence of intrauterine growth restriction (IUGR). LO-PE with IUGR showed higher correlation with SGA and LO-PE without IUGR with LGA placentas. Whereas changes in placental transcriptome in SGA, LGA and GD cases were less prominent, the overall profiles of expressional disturbances overlapped among pregnancy complications providing support to shared placental responses. The dataset represent a rich catalogue for potential biomarkers and therapeutic targets. PMID- 26268792 TI - The influence of rituximab, high-dose therapy followed by autologous stem cell transplantation, and age in patients with primary CNS lymphoma. AB - For patients with diffuse large B cell lymphoma without the involvement of the CNS, the addition of rituximab to standard chemotherapy has significantly improved survival. In this single-center, retrospective analysis, a total of 81 primary CNS lymphoma (PCNSL) patients treated in our institution between 2000 and 2011 were included. Beside first-line chemotherapy with or without rituximab, we evaluated the impact of age (<=/>60 years), autologous stem cell transplantation (ASCT +/-), and other factors upon overall survival (OS) and progression-free survival (PFS). In patients treated with rituximab (n = 27), 3-year OS was 77.8 % (95 % confidence interval (CI) 62-93 %). In contrast, in patients treated without rituximab (n = 52), 3-year OS was only 39.9 % (CI 27-53 %, Fig. 1). The difference in OS was significant in the univariate (p = 0.002) as well as in the multivariate analysis (p = 0.049, hazard ratio (HR) = 0.248). Patients <=60 years of age (n = 28) had a 3-year OS of 78.2 % (CI 63-94 %); in patients >60 years (n = 51), 3-year OS was 38.7 % (CI 25-52 %). Patients who received high-dose therapy and ASCT had a 3-year OS of 85.2 % (CI 72-99 %), and 65.1 % were alive up to the time of analysis (range 9-131 months). Without ASCT, median OS was only 16 months (CI 11-21) and 3-year OS was 35.2 % (CI 22-48 %). Age and ASCT were significantly associated with better OS in univariate (p = 0.002 and p < 0.001) as well in multivariate analysis (p = 0.004, HR = 0.023 and p = 0.001, HR = 0.014). Rituximab treatment, ASCT, and age are independent prognostic factors for OS in the first-line treatment of PCNSL. PMID- 26268793 TI - A new cassane diterpenoid from the seeds of Caesalpinia decapetala. AB - Phytochemical investigation on the seeds of Caesalpinia decapetala led to the isolation of a new cassane diterpenoid with an unusual O bridge between C-19 and C-20, named phanginin Q (1), together with three known cassane diterpenoids, caesaljapin (2), caesaldekarin A (3), and caesaldekarin B (4). The structure of the new compound was elucidated by spectroscopic methods, including (1)H NMR, (13)C NMR, HSQC, (1)H - (1)H COSY, HMBC, NOESY, and HR-ESI-MS. PMID- 26268794 TI - Advancing perspectives on parity-mode evolution. PMID- 26268795 TI - Giant panda (Ailuropoda melanoleuca) sperm morphometry and function after repeated freezing and thawing. AB - This work examines the effects of subsequent cycles of freezing-thawing on giant panda (Ailuropoda melanoleuca) sperm morphometry and function, and assesses whether density-gradient centrifugation (DGC) can increase the number of freezing thawing cycles this sperm can withstand. A sperm sample was collected by electroejaculation from a mature giant panda and subjected to five freezing thawing cycles. Although repeated freezing-thawing negatively affected (P < 0.05) sperm motility and membrane integrity, in both nonselected and DCG-selected sperm samples, >60% of the sperm cells in both treatments showed acrosome integrity even after the fifth freezing cycle. In fresh semen, the sperm head length was 4.7 MUm, the head width 3.6 MUm, area 14.3 MUm(2) and perimeter length 14.1 MUm. The present results suggest that giant panda sperm trends to be resistant to repeated freezing-thawing, even without DGC selection. PMID- 26268796 TI - Defects in Metal-Organic Frameworks: Challenge or Opportunity? AB - Metal-organic framework (MOF) materials are nanoporous materials whose crystalline character has made them attractive targets for synthesis of new materials and potential use in a diverse set of applications. The vast majority of studies of MOFs envision these materials as having ideal crystal structures. This Perspective gives an overview of the current understanding of defects in MOFs. Compared to related materials such as zeolites, the ability to detect and control defects in MOFs is nascent. Nevertheless, it is likely that defects will play a vital role in a number of contexts where MOFs are of widespread interest, so advancing our understanding of these structural features will be important in coming years. Potential origins of point defects, plane defects, and surface defects are discussed. The difficulty of defect detection in metal-organic frameworks is discussed and useful paths for future work are provided. PMID- 26268797 TI - First complete genome of an Ambidensovirus; Cherax quadricarinatus densovirus, from freshwater crayfish Cherax quadricarinatus. AB - In 1999, the causative agent of an epizootic in Cherax quadricarinatus was described, and given the provisional name Cherax quadricarinatus parvovirus-like. Sequencing of the 6334 nt genome identified three open-reading frames on the top strand coding NS3 (35.55 kDa), NS1 (67.36 kDa) and NS2 (35.18 kDa) and on the bottom strand a single open reading frame which most likely encodes 4 structural proteins. Motifs characteristic of the Densovirinae were found in the ORFs. Phylogenetic analysis of the amino acids in NS1 places the genome in the genus Ambidensovirus, most closely related to the marine sea star densovirus (75%, E=0.0) and distantly related to Acheta domestica densovirus (44.1%). The virus name is proposed as species Decapod ambidensovirus, variant Cherax quadricarinatus densovirus. This is the first Ambidensovirus to be found in decapod crustaceans and the first of the subfamily Densovirinae to be sequenced from a freshwater crayfish. Cherax quadricarinatus densovirus and sea star densovirus are the first highly related Densovirinae to infect phylogenetically disparate hosts and are thus far, unique among the Densovirinae. PMID- 26268798 TI - Perceptions of pharmacists and patients on information provision and their influence on patient satisfaction in Japanese community pharmacies. AB - RATIONALE, AIMS AND OBJECTIVES: The provision of information is now considered a major area in pharmacist-patient interactions. However, few reports have simultaneously evaluated patient and pharmacist perceptions with regard to the pharmacist's information provision. The aims were to clarify the perceptions of pharmacists and patients regarding information provision and the level of influence of those perceptions on patient satisfaction. METHODS: A cross sectional survey with respect to information provision was conducted for patients and pharmacists in community pharmacies in Fukuoka Prefecture, Japan. In total, 407 patient-pharmacist pairs were included in a t-test and multilevel analysis. RESULTS: The levels of patient perception regarding information provision were significantly higher than the levels of pharmacist perception in all variables. The pharmacists' perceived level of information provision concerning medication effects had a negative and significant association with patient satisfaction, while the patients' perceived level of information provision by the pharmacist had a positive and significant association with patient satisfaction. Higher patient expectations regarding the level of information provision concerning medication side effects and older age of the pharmacist were adversely related to patient satisfaction. Both pharmacist and patient perceptions of the information provision by pharmacists personalized to the patient had positive associations with patient satisfaction. CONCLUSIONS: Pharmacist perceptions related to the information provision were not associated with patient satisfaction. The present study highlights accurate information provision, building good patient-pharmacist relationships, and improving pharmaceutical care in community pharmacy settings. PMID- 26268799 TI - Clinical pathway for the screening, assessment and management of anxiety and depression in adult cancer patients: Australian guidelines. AB - PURPOSE: A clinical pathway for anxiety and depression in adult cancer patients was developed to guide best practice in Australia. METHODS: The pathway was based on a rapid review of existing guidelines, systematic reviews and meta-analyses, stakeholder interviews, a Delphi process with 87 multidisciplinary stakeholders and input from a multidisciplinary advisory panel. RESULTS: The pathway recommends formalized routine screening for anxiety and depression in patients with cancer at key points in the patient's journey. The Edmonton Symptom Assessment System or distress thermometer with problem checklist is recommended as brief screening tools, combined with a more detailed tool, such as the Hospital Anxiety and Depression Scale, to identify possible cases. A structured clinical interview will be required to confirm diagnosis. When anxiety or depression is identified, it is recommended that one person in a treating team takes responsibility for coordinating appropriate assessment, referral and follow up (not necessarily carrying these out themselves). A stepped care model of intervention is proposed, beginning with the least intensive available that is still likely to provide significant health gain. The exact intervention, treatment length and follow-up timelines, as well as professionals involved, are provided as a guide only. Each service should identify their own referral network based on local resources and current service structure, as well as patient preference. DISCUSSION: This clinical pathway will assist cancer services to design their own systems to detect and manage anxiety and depression in their patients, to improve the quality of care. PMID- 26268800 TI - Relating Worry and Executive Functioning During Childhood: The Moderating Role of Age. AB - The associations between worry and executive functioning across development have not been previously explored. Examining the interrelationships between these variables in childhood may further elucidate the cognitive nature of worry as well as its developmental course. Hypotheses predicted that difficulties with executive functioning would correlate with child worry; based on extant literature, age-related hypotheses were proposed for particular aspects of executive functioning. Children (N = 130) participated in the present study. Difficulties with executive functioning and child worry were assessed. Results demonstrated that each executive functioning subscale correlated with worry. The relations between worry and several facets of executive functioning were no longer significant at older ages, while the relations between worry and the facets of inhibition, shifting, and emotional control did not demonstrate age related interaction effects. Overall, the findings suggest that worry is associated with executive functioning at young ages and that this association takes distinct forms during different childhood stages. PMID- 26268802 TI - Institution-specific risk of papillary thyroid carcinoma in atypia/follicular lesion of undetermined significance. AB - BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) is used in surgical decision-making according to malignancy risk in each category. Malignancy risk in atypia/follicular lesion of undetermined significance (AUS/FLUS) is estimated in BSRTC to be 5% to 15%, but institutional data have varied widely. METHODS: We conducted a post-BSRTC 4-year retrospective analysis of index thyroid nodule cytology and histopathology in an academic head and neck endocrine surgery setting. RESULTS: Of 2939 thyroid cytology reports from 1944 patients, the most advanced BSRTC category was AUS/FLUS in 233 patients (12.0%) of which 187 went to thyroidectomy. In AUS/FLUS, the upper and lower boundary estimates of the malignancy rate were 46% and 37%, accordingly. The malignancy rate did not vary significantly by cytopathologist or cytopathologic features. CONCLUSION: Malignancy rates in AUS/FLUS vary by institution from 6% to 46%. Given the subjective nature of thyroid cytopathology and interpretation of the BSRTC categories, guidelines should encourage the use of institution-specific data on malignancy risk in treatment decisions. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1210-E1215, 2016. PMID- 26268801 TI - The mycobacterial iron-dependent regulator IdeR induces ferritin (bfrB) by alleviating Lsr2 repression. AB - Emerging evidence indicates that precise regulation of iron (Fe) metabolism and maintenance of Fe homeostasis in Mycobacterium tuberculosis (Mtb) are essential for its survival and proliferation in the host. IdeR is a central transcriptional regulator of Mtb genes involved in Fe metabolism. While it is well understood how IdeR functions as a repressor, how it induces transcription of a subset of its targets is still unclear. We investigated the molecular mechanism of IdeR mediated positive regulation of bfrB, the gene encoding the major Fe-storage protein of Mtb. We found that bfrB induction by Fe required direct interaction of IdeR with a DNA sequence containing four tandem IdeR-binding boxes located upstream of the bfrB promoter. Results of in vivo and in vitro transcription assays identified a direct repressor of bfrB, the histone-like protein Lsr2. IdeR counteracted Lsr2-mediated repression in vitro, suggesting that IdeR induces bfrB transcription by antagonizing the repressor activity of Lsr2. Together, these results elucidate the main mechanism of bfrB positive regulation by IdeR and identify Lsr2 as a new factor contributing to Fe homeostasis in mycobacteria. PMID- 26268803 TI - Mucilaginibacter ginsengisoli sp. nov., isolated from a ginseng-cultivated soil. AB - A dark-pink-coloured bacterial strain, B4Y-8T, was isolated from a soil cultivated with ginseng. The 16S rRNA gene sequence of this strain showed highest similarity with Mucilaginibacter litoreus BR-18T (96.8 %), Mucilaginibacter lutimaris BR-3T (96.6 %) and Mucilaginibacter defluvii A5T (96.2 %) among the type strains of species of the genus Mucilaginibacter. Strain B4Y-8T was a strictly aerobic, Gram-stain-negative, non-motile, short-rod-shaped bacterium producing a large amount of extracellular polymeric substance. The strain grew at 10-35 degrees C (optimum, 25 degrees C), at pH 3.0-11.0 (optimum, pH 7.0) and in the presence of 0-1 % (w/v) NaCl (optimum, 0 %). The DNA G+C content of strain B4Y-8T was 49.0 mol%. It contained menaquinone 7 (MK-7) as the major isoprenoid quinone, and summed feature 3 (C16 : 1omega6c and/or C16 : 1omega7c) and iso-C15 : 0 as the major fatty acids. On the basis of evidence from the present polyphasic taxonomic study, strain B4Y-8T should be classified as representing a novel species of the genus Mucilaginibacter, for which the name Mucilaginibacter ginsengisoli sp. nov. is proposed. The type strain is B4Y-8T ( = KACC 18152T = JCM 30759T). PMID- 26268804 TI - Assessing the effectiveness of household-level focal mass drug administration and community-wide mass drug administration for reducing malaria parasite infection prevalence and incidence in Southern Province, Zambia: study protocol for a community randomized controlled trial. AB - BACKGROUND: Mass drug administration (MDA) and focal MDA (fMDA) using dihydroartemisinin plus piperaquine (DHAp), represent two strategies to maximize the use of existing information to achieve greater clearance of human infection and reduce the parasite reservoir, and provide longer chemoprophylactic protection against new infections. The primary aim of this study is to quantify the relative effectiveness of MDA and fMDA with DHAp against no mass treatment (standard of care) for reducing Plasmodium falciparum prevalence and incidence. METHODS/DESIGN: The study will be conducted along Lake Kariba in Southern Province, Zambia; an area of low to moderate malaria transmission and high coverage of vector control. A community randomized controlled trial (CRCT) of 60 health facility catchment areas (HFCAs) will be used to evaluate the impact of two rounds of MDA and fMDA interventions, relative to a control of no mass treatment, stratified by high and low transmission. Community residents in MDA HFCAs will be treated with DHAp at the end of the dry season (round one: November to December 2014) and the beginning of the rainy season (round two: February to March 2015). Community residents in fMDA HFCAs will be tested during the same two rounds for malaria parasites with a rapid diagnostic test; all positive individuals and all individuals living in their household will be treated with DHAp. Primary outcomes include malaria parasite prevalence (n = 5,640 children aged one month to under five-years-old), as measured by pre- and post-surveys, and malaria parasite infection incidence (n = 2,250 person-years among individuals aged three months and older), as measured by a monthly longitudinal cohort. The study is powered to detect approximately a 50 % relative reduction in these outcomes between each intervention group versus the control. DISCUSSION: Strengths of this trial include: a robust study design (CRCT); cross-sectional parasite surveys as well as a longitudinal cohort; and stratification of high and low transmission areas. Primary limitations include: statistical power to detect only a 50 % reduction in primary outcomes within high and low transmission strata; potential for contamination; and potential for misclassification of exposure. TRIAL REGISTRATION: Identifier: Clinicaltrials.gov: NCT02329301 . Registration date: 30 December 2014. PMID- 26268805 TI - Discovery of Some Piperine-Based Phenylsulfonylhydrazone Derivatives as Potent Botanically Narcotic Agents. AB - By structural modification of piperine, some piperine-based phenylsulfonylhydrazone derivatives exhibited an unprecedented and potent narcotic activity against the oriental armyworm, Mythimna separata (Walker). The ND50 values of compounds 6c and 6e against the third-instar larvae of M. separata, which were more potent than those of wilfortrine and wilforgine, were 0.0074 MUmol (after 3.5 h), and 0.0075 MUmol (after 7 h) per larvae, respectively. By transmission electron microscope, it demonstrated that mitochondria were vacuolated and swollen in the ganglion cell of M. separata after treatment with 6c. More importantly, 6c selectively displayed the inhibition activity on acetylcholine esterase (AchE) of M. separata. This work paved the way for further studying the insecticidal mechanism of 6c as a new and promising botanical narcotic agent. PMID- 26268806 TI - Cardiovascular risk prediction in HIV-infected patients: comparing the Framingham, atherosclerotic cardiovascular disease risk score (ASCVD), Systematic Coronary Risk Evaluation for the Netherlands (SCORE-NL) and Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) risk prediction models. AB - OBJECTIVES: The aim of the study was to compare the predictions of five popular cardiovascular disease (CVD) risk prediction models, namely the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) model, the Framingham Heart Study (FHS) coronary heart disease (FHS-CHD) and general CVD (FHS-CVD) models, the American Heart Association (AHA) atherosclerotic cardiovascular disease risk score (ASCVD) model and the Systematic Coronary Risk Evaluation for the Netherlands (SCORE-NL) model. METHODS: A cross-sectional design was used to compare the cumulative CVD risk predictions of the models. Furthermore, the predictions of the general CVD models were compared with those of the HIV specific D:A:D model using three categories (< 10%, 10-20% and > 20%) to categorize the risk and to determine the degree to which patients were categorized similarly or in a higher/lower category. RESULTS: A total of 997 HIV infected patients were included in the study: 81% were male and they had a median age of 46 [interquartile range (IQR) 40-52] years, a known duration of HIV infection of 6.8 (IQR 3.7-10.9) years, and a median time on ART of 6.4 (IQR 3.0 11.5) years. The D:A:D, ASCVD and SCORE-NL models gave a lower cumulative CVD risk, compared with that of the FHS-CVD and FHS-CHD models. Comparing the general CVD models with the D:A:D model, the FHS-CVD and FHS-CHD models only classified 65% and 79% of patients, respectively, in the same category as did the D:A:D model. However, for the ASCVD and SCORE-NL models, this percentage was 89% and 87%, respectively. Furthermore, FHS-CVD and FHS-CHD attributed a higher CVD risk to 33% and 16% of patients, respectively, while this percentage was < 6% for ASCVD and SCORE-NL. CONCLUSIONS: When using FHS-CVD and FHS-CHD, a higher overall CVD risk was attributed to the HIV-infected patients than when using the D:A:D, ASCVD and SCORE-NL models. This could have consequences regarding overtreatment, drug-related adverse events and drug-drug interactions. PMID- 26268808 TI - Should all NHS premises provide free access to wi-fi? PMID- 26268807 TI - Sex differences in medico-legal action against doctors: a systematic review and meta-analysis. AB - BACKGROUND: The relationship between male sex and poor performance in doctors remains unclear, with high profile studies showing conflicting results. Nevertheless, it is an important first step towards understanding the causes of poor performance in doctors. This article aims to establish the robustness of the association between male sex and poor performance in doctors, internationally and over time. METHODS: The electronic databases MEDLINE, EMBASE, and PsycINFO were searched from inception to January 2015. Backward and forward citation searching was performed. Journals that yielded the majority of the eligible articles and journals in the medical education field were electronically searched, along with the conference and poster abstracts from two of the largest international medical education conferences. Studies reporting original data, written in English or French, examining the association between sex and medico-legal action against doctors were included. Two reviewers independently extracted study characteristics and outcome data from the full texts of the studies meeting the eligibility criteria. Study quality was assessed using the Newcastle-Ottawa scale. A random effect meta-analysis model was used to summarize and assess the effect of doctors' sex on medico-legal action. Extracted outcomes included disciplinary action by a medical regulatory board, malpractice experience, referral to a medical regulatory body, complaints received by a healthcare complaints body, criminal cases, and medico-legal matter with a medical defence organisation. RESULTS: Overall, 32 reports examining the association between doctors' sex and medico-legal action were included in the systematic review (n=4,054,551), of which 27 found that male doctors were more likely to have experienced medico-legal action. 19 reports were included in the meta-analysis (n=3,794,486, including 20,666 cases). Results showed male doctors had nearly two and a half times the odds of being subject to medico-legal action than female doctors. Heterogeneity was present in all meta-analyses. CONCLUSION: Male doctors are more likely to have had experienced medico-legal actions compared to female doctors. This finding is robust internationally, across outcomes of varying severity, and over time. PMID- 26268809 TI - The effects of preferential A- and C-fibre blocks and T-type calcium channel antagonist on detection of low-force monofilaments in healthy human participants. AB - BACKGROUND: A myriad of studies have argued that tactile sensibility is underpinned exclusively by large myelinated mechanoreceptors. However, the functional significance of their slow-conducting counterparts, termed C-low threshold mechanoreceptors (C-LTMRs), remains largely unexplored. We recently showed the emergence of brush- and vibration-evoked allodynia in human hairy and glabrous skin during background muscle pain. The allodynia persisted following the preferential blockade of myelinated fibres but was abolished by the preferential blockade of cutaneous C fibres, thereby suggesting a pathway involving hairy skin C-LTMRs and their functional counterparts in glabrous skin in this phenomenon. In the present study, we tested the effects of preferential A and C-fibre conduction blocks and pharmacological blockade of T-type calcium channel Cav3.2 (expressed selectively on small-fibre LTMRs) on monofilament detection thresholds in healthy participants by compression, low-dose intradermal anaesthesia (xylocaine 0.25 %) and selective T-channel antagonist, TTA-A2. RESULTS: We found that all participants could detect monofilament contacts (as low as 1.6 mN) within the innocuous tactile range regardless of the preferential blockade of myelinated fibres. Furthermore, during the compression block no subject reported a switch in modality from touch to pain. That is, the low-force monofilament contacts were always perceived as non-painful. However, there was a small but significant elevation of monofilament thresholds (~2 mN) in the glabrous skin following the compression block. Importantly, no differences were found in the thresholds across hairy and glabrous regions while the myelinated fibres were conducting or not. The preferential blockade of C fibres in the glabrous skin (with myelinated fibres intact) also resulted in a small but significant elevation of tactile thresholds. Furthermore, the use of T-channel blocker in the glabrous skin during compression block of myelinated fibres resulted in complete abolition of monofilament sensibility within the innocuous tactile range (tested up to ~20 mN). CONCLUSIONS: These observations suggest that C-LTMRs need not be regarded as a redundant tactile system, but appear to complement normal large-myelinated-fibre tactile function. Convergent findings in glabrous and hairy skin lend support for an underlying system of innocuous mechanoreception with Cav3.2-expressing unmyelinated fibres. PMID- 26268810 TI - Auditory temporal resolution is linked to resonance frequency of the auditory cortex. AB - A brief silent gap embedded in an otherwise continuous sound is missed by a human listener when it falls below a certain threshold: the gap detection threshold. This can be interpreted as an indicator that auditory perception is a non continuous process, during which acoustic input is fragmented into a discrete chain of events. Current research provides evidence for a covariation between rhythmic properties of speech and ongoing rhythmic activity in the brain. Therefore, the discretization of acoustic input is thought to facilitate speech processing. Ongoing oscillations in the auditory cortex are suggested to represent a neuronal mechanism which implements the discretization process and leads to a limited auditory temporal resolution. Since gap detection thresholds seem to vary considerably between individuals, the present study addresses the question of whether individual differences in the frequency of underlying ongoing oscillatory mechanisms can be associated with auditory temporal resolution. To address this question we determined an individual gap detection threshold and a preferred oscillatory frequency for each participant. The preferred frequency of the auditory cortex was identified using an auditory steady state response (ASSR) paradigm: amplitude-modulated sounds with modulation frequencies in the gamma range were presented binaurally; the frequency which elicited the largest spectral amplitude was considered the preferred oscillatory frequency. Our results show that individuals with higher preferred auditory frequencies perform significantly better in the gap detection task. Moreover, this correlation between oscillation frequency and gap detection was supported by high test-retest reliabilities for gap detection thresholds as well as preferred frequencies. PMID- 26268811 TI - Rare CFH mutations and early-onset age-related macular degeneration. PMID- 26268812 TI - A ferrocene-switched electrochemiluminescence "off-on" strategy for the sensitive detection of cardiac troponin I based on target transduction and a DNA walking machine. AB - A ferrocene-switched electrochemiluminescence "off-on" sensor is proposed on the basis of target transduction and a DNA walking machine for the sensitive detection of cardiac troponin I (cTnI). The proposed method offers high selectivity with a low detection limit of 0.016 pg mL(-1), and provides a universal platform for detecting a wide range of targets, including other proteins and DNAs, by changing the molecular recognition elements to the corresponding antibodies, aptamers or DNA probes. PMID- 26268814 TI - Neurogenic thoracic outlet syndrome due to subclavius posticus muscle with dynamic brachial plexus compression: a case report. AB - BACKGROUND: Neurogenic thoracic outlet syndrome is an underestimated cause of brachial weakness and pain. The subclavius posticus muscle (SPM) is an aberrant muscle originating from the medial aspect of the first rib reaching to superior border of the scapula, which may cause, depending on its activation, dynamic compression of the brachial plexus. CASE PRESENTATION: In the present study, we report about a 32-year-old male caucasian patient with weakness in radial deviation of his left hand. An isolated macrodactyly of his left middle finger had been operated twice. Electroneurography showed a carpal-tunnel-syndrome (CTS) on the left side. MRI of the brachial plexus revealed an additional muscle in the costoclavicular space, identified as SPM. To our knowledge, this is the second case report of a neurogenic thoracic outlet syndrome due to SPM, and the first case described with isolated macrodactyly and CTS in the same patient. CONCLUSION: If complaints about hand weakness are only reported in cases of distinct hand positions, a dynamic compression of the brachial plexus by SPM may be the cause. A neurogenic thoracic outlet syndrome may facilitate the development of CTS. PMID- 26268815 TI - Association of HLA-DRB1 alleles with clinical responses to the anti-interleukin 17A monoclonal antibody secukinumab in active rheumatoid arthritis. AB - OBJECTIVE: To assess whether preliminary findings of associations between the HLA DRB1*04 and HLA-DRB1* shared epitope (SE) allelic groups and response to the anti IL-17A mAb secukinumab in RA were reproducible in an independent RA cohort. METHODS: Biologic-naive subjects (n = 100) with RA by 2010 criteria with tender/swollen joint counts (each >=6) and high-sensitivity CRP (hsCRP) >10 mg/l were randomized 2:1 to secukinumab 10 mg/kg i.v. or placebo every 2 weeks until week 10. Potential associations with treatment response to secukinumab at week 12 (DAS28-CRP change from baseline by analysis of covariance, ACR20 response rate by logistic regression) were assessed for HLA-DRB1*04 (primary end point), HLA DRB1*SE and HLA-DRB1 position 11 V/L (HLA-DRB1*pos11 V/L) allelic groups, and baseline levels of hsCRP, RF and anti-CCP. RESULTS: Secukinumab was significantly more effective than placebo in reducing DAS28-CRP (-2.41 vs -0.71; P < 0.0001) and producing ACR20 responses (87.1% vs 25.0%; P < 0.0001) at week 12. The HLA DRB1*04 allelic group was not significantly related to secukinumab response vs placebo. For change from baseline in DAS28-CRP, HLA-DRB1*SE (P = 0.003) and HLA DRB1*pos11 V/L (P = 0.002) allelic groups were associated with positive treatment response. Higher RF levels, but not anti-CCP positivity, were significantly associated with DAS28-CRP reductions (P = 0.015) and ACR20 (P = 0.008) responses. Secukinumab was well tolerated. CONCLUSION: Secukinumab significantly reduced signs and symptoms of RA vs placebo. As the HLA-DRB1*SE and HLA-DRB1*pos11 V/L results were driven by lack of placebo response in carriers, the hypothesis of clinical utility for HLA-DRB1* allelic groups in RA anti-IL-17A short-term response prediction could not be corroborated. TRIAL REGISTRATION: ClinicalTrials.gov; https://clinicaltrials.gov/; NCT01426789. PMID- 26268816 TI - Immunogenicity of biologic agents in rheumatoid arthritis patients: lessons for clinical practice. AB - Anti-drug antibodies (ADAbs) develop in up to a third of patients treated with biologic agents, with such immunogenicity being one of the main reasons for the loss of efficacy observed in an important proportion of patients treated with such agents. The appearance of ADAbs has consequences in terms of efficacy and tolerance of the biodrug: the development of ADAbs is associated with a poorer clinical response and with an increased risk of adverse effects. Formation of ADAbs has been observed with all biologic DMARDs, but anti-TNF agent mAbs appear to be the largest contributors, independent of humanization of the antibody. ADAb identification is technically difficult and not standardized, partly explaining important variations between published studies. A variety of factors can influence the risk of ADAb appearance, some of which are linked to the treatment strategy, such as the combination with synthetic DMARDs or the rhythm of administration of the biodrug, whereas other factors are dependent on the patient, such as the level of inflammation at onset or body weight. The detection of these antibodies and/or the dosage of the biologic agent itself could have consequences for the bedside practice of clinicians and should be well understood. This review of the literature proposes an overview of the data published on the subject to help clinicians manage the biodrugs according to these new concepts. PMID- 26268813 TI - Enantioselective and Enantiospecific Transition-Metal-Catalyzed Cross-Coupling Reactions of Organometallic Reagents To Construct C-C Bonds. PMID- 26268817 TI - Gay and bisexual men's awareness and knowledge of treatment as prevention: findings from the Momentum Health Study in Vancouver, Canada. AB - INTRODUCTION: Awareness and knowledge of treatment as prevention (TasP) was assessed among HIV-positive and HIV-negative gay, bisexual and other men who have sex with men (GBMSM) in Vancouver, Canada. METHODS: Baseline cross-sectional survey data were analyzed for GBMSM enrolled, via respondent-driven sampling (RDS), in the Momentum Health Study. TasP awareness was defined as ever versus never heard of the term "TasP." Multivariable logistic regression identified covariates of TasP awareness. Among those aware of TasP, men's level of knowledge of TasP was explored through an examination of self-perceived knowledge levels, risk perceptions and short-answer definitions of TasP which were coded as "complete" if three TasP-related components were identified (i.e. HIV treatment, viral suppression and prevention of transmission). Information source was also assessed. Analyses were stratified by HIV status and RDS adjusted. RESULTS: Of 719 participants, 23% were HIV-positive, 68% Caucasian and median age was 33 (Interquartile range (IQR) 26,47). Overall, 46% heard of TasP with differences by HIV status [69% HIV-positive vs. 41% HIV-negative GBMSM (p<0.0001)]. In adjusted models: HIV-positive GBMSM were more likely to have heard of TasP if they were Canadian born, unemployed, not using party drugs and had higher CD4 counts; HIV negative GBMSM were more likely to have heard of TasP if they were Caucasian (vs. Aboriginal), students, had higher education, a regular partner and multiple sexual partners. Among those aware of TasP 91% of HIV-positive and 69% of HIV negative GBMSM (p<0.0001) felt they knew "a lot" or "a bit in general" about TasP; 64 and 41% (p=0.002) felt HIV treatment made the risk of transmission "a lot lower"; and 21 and 13% (p<0.0001) demonstrated "complete" TasP definitions. The leading information source was doctors (44%) for HIV-positive GBMSM and community agencies (38%) for HIV-negative GBMSM, followed by gay media for both populations (34%). CONCLUSIONS: Nearly half of GBMSM in this study reported having heard of TasP, yet only 14% demonstrated complete understanding of the concept. Variations in TasP awareness and knowledge by HIV status, and key socio demographic, behavioural and clinical factors, highlight a need for health communication strategies relevant to diverse communities of GBMSM in order to advance overall TasP health literacy. PMID- 26268818 TI - Radical surgery versus standard surgery for primary cytoreduction of bulky stage IIIC and IV ovarian cancer: an observational study. AB - BACKGROUND: The aim of this study was to evaluate the survival benefit of radical surgery with additional extensive upper abdominal procedures (EUAS) for the treatment of stage IIIC and IV ovarian cancer with bulky upper abdominal disease (UAD). METHODS: An observational study was conducted between 2009 and 2012 involving two different surgical teams. Team A was composed of the "believers" in EUAS and Team B the "non-believers" in EUAS. Patients were divided into a radical surgery group (EUAS group) or a standard surgery group (non-EUAS group) according to whether or not they had received EUAS. All patients underwent primary cytoreductive surgery with the goal of optimal debulking (<= 1 cm); this was reviewed in the pelvis, middle abdomen, and upper abdomen. The baseline for the two groups was optimal cytoreduction in both the pelvis and middle abdomen. Progression-free survival (PFS) was evaluated. RESULTS: Radical surgery was performed in 70.7% (82/116) and 12.7% (30/237) of the patients by Teams A and B, respectively. The study groups had similar clinicopathologic characteristics. The median PFS and OS were significantly improved in the radical surgery group, compared with standard surgery groups (PFS: 19.5 vs. 13.3 months, HR: 0.61; 95% CI: 0.46-0.80, P < 0.001; OS: not reached vs. 39.3 months, HR: 0.47; 95% CI: 0.30 0.72, P < 0.001). Positive predictors of complete cytoreduction were treatment with neoadjuvant chemotherapy, improved American Society of Anesthesiologists performance status, and the absence of bowel mesenteric carcinomatosis. CONCLUSIONS: Radical surgery lengthens the PFS and overall survival times of ovarian cancer patients with bulky UAD. However, a well-designed randomized trial is needed to confirm the present results. PMID- 26268819 TI - Long-term survival and preprocedural predictors of mortality in high surgical risk patients undergoing percutaneous mitral valve repair. AB - OBJECTIVES: To evaluate long-term survival in high surgical risk patients undergoing percutaneous mitral valve repair (MVR) using the MitraClip((r)) system and to identify preprocedural predictors of long-term mortality. BACKGROUND: Data for long-term survival and preprocedural predictors of mortality after percutaneous MVR in high surgical risk patients are sporadic. METHODS: From January 2009 to April 2013, 136 consecutive high surgical risk patients, with symptomatic moderate-to-severe or severe mitral regurgitation (MR), underwent percutaneous MVR using the MitraClip system. Cardiac and overall survival was determined at one and 2 years postprocedure. Univariate and multivariate analysis was performed to identify preprocedural predictors of long-term mortality. RESULTS: One year postprocedure, cardiac and overall survival was 86.7% and 84.6%, respectively and at 2 years cardiac and overall survival was 77.7% and 74.8%, respectively. In univariate analysis advanced age, lower body mass index, impaired renal function, elevated levels of log-N-terminal-pro-brain-natriuretic peptide (log-NTproBNP), poor performance in functional tests (New York Heart Association (NYHA) class) and high logistic Euroscore (LES) and Society of Thoracic Surgeons (STS) score were identified as preprocedural predictors of long term cardiac mortality. In multivariate analysis preoperative NYHA class III and IV, elevated levels of log-NTproBNP and advanced age predicted long-term cardiac mortality. CONCLUSIONS: Percutaneous MVR using the MitraClip system has favorable long-term survival rates in high surgical risk patients. Preprocedural NYHA functional class III and IV, elevated log-NTproBNP levels and advanced age predict higher long-term cardiac mortality and should be considered during patient selection. PMID- 26268821 TI - Heavy hematuria requiring cystectomy in a patient with hemophilia A: a case report and literature review. AB - BACKGROUND: Hemophilia A is an X-linked recessive disorder caused by a deficiency in factor VIII. Hemophilia A affects 1 in 5,000-10,000 males. Hematuria is frequent in hemophilia. Hematuria in hemophilia is generally considered benign and manageable with conservative therapy; however, severe hematuria requiring surgical therapy has rarely been reported. CASE PRESENTATION: A 60-year-old male with hemophilia A presented with persistent gross hematuria of unknown cause. He was treated with recombinant factor VIII products, followed by several conservative therapies as follows: clot evacuation by vesicoclysis, continuous bladder irrigation with normal saline, and intravesical instillation of aluminum hydroxide/magnesium hydroxide (Maalox); however, these failed to resolve the hemorrhaging. The patient was offered and consented to cystectomy with an ileal conduit. Intraoperative clotting was normal with the infusion of adequate recombinant factor VIII products and transfusion of fresh-frozen plasma, and the procedure was performed safely. After surgery, the patient had blood in his stool several times. No bleeding site was demonstrated in the colon by colonoscopy and (99m)Technetium-human serum albumin-diethylenetriaminepenta-acetic acid scintigraphy demonstrated that the extravasation of radioactive isotope was detected at the anal side of terminal ileum but not at the oral side. These findings were suspected to be bleeding from the ileoileal anastomosis. However, the bleeding was managed with recombinant factor VIII products. CONCLUSIONS: Cystectomy in hemophilia may be safe, if monitored appropriately. Urinary diversion using the intestine may be avoided because anastomotic hemorrhage may become a problem. PMID- 26268822 TI - PGC-1alpha gene transfer improves muscle function in dystrophic muscle following prolonged disease progress. AB - NEW FINDINGS: What is the central question of this study? Peroxisome proliferator activated receptor gamma coactivator 1alpha (PGC-1alpha) gene transfer as a treatment for Duchenne muscular dystrophy is efficacious even with advanced disease. What is the main finding and its importance? PGC-1alpha pathway activation strategies may be most effective when initiated at the earliest possible time. Duchenne muscular dystrophy is a progressive and fatal muscle wasting disease caused by a dystrophin deficiency. We previously found that gene transfer of peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) increased abundance of utrophin and increased mitochondrial biogenesis using prevention and rescue treatment protocols. Our purpose in this investigation was to determine the extent to which PGC-1alpha gene transfer would rescue dystrophic muscle following prolonged disease progression. One-year-old mdx mice from our colony were injected in one hindlimb with a virus driving expression of PGC-1alpha, while the contralateral limb was injected with empty capsid. Three months after viral gene transfer, PGC-1alpha expression was 40-fold greater than in contralateral limbs. Specific tension was increased by ~ 60% (P < 0.05), and force produced during the final contraction of a fatigue protocol was 60% greater in treated soleus muscles compared with contralateral control muscles (P < 0.05). Histopathology was not improved by PGC-1alpha overexpression. Also, while there were numerous differences in gene expression between healthy and dystrophic muscle, there were relatively few differences between PGC-1alpha treated limbs and contralateral control limbs. These data indicate that PGC 1alpha pathway activation may interrupt the disease process even if initiated within the context of advanced disease; however, the mechanism that underlies this functional correction is not apparent. PMID- 26268823 TI - Functional imaging for chest pain in the emergency room: To do or not to do? PMID- 26268824 TI - Comparison of stress cardiovascular magnetic resonance imaging (CMR) with stress nuclear perfusion for the diagnosis of coronary artery disease. AB - OBJECTIVES: To assess the diagnostic performance of stress cardiac magnetic resonance (stress CMR) vs stress single-photon emission computed tomography (SPECT) in patients presenting to the emergency department (ED) with chest pain. BACKGROUND: SPECT imaging is the most utilized outpatient procedure in the United States. The diagnostic accuracy of SPECT can be limited by soft tissue attenuation and low spatial resolution. Stress CMR has much higher spatial resolution and without the susceptibility to soft tissue attenuation. METHODS: Eighty-seven patients without a history of CAD presenting to the ED with chest pain were prospectively enrolled. Patients underwent both stress CMR and stress SPECT imaging within 12 hours of presentation. Both the stress imaging tests were interpreted immediately for clinical purposes and coronary angiography was performed if either was abnormal. Patients were considered to have significant CAD if identified by angiography (>=50%) or if a cardiac event (cardiac death, myocardial infarction or revascularization) occurred during follow-up (mean 2.6 +/- 1.1 years). RESULTS: Thirty-seven patients were referred for coronary angiography; 29 due to a positive stress test and eight patients for persistent chest pain despite two negative stress tests. There were 22 patients who had significant CAD (>=50%). The remaining patients were followed for 2.6 +/- 1.1 years. At the conclusion of the follow-up period, there were four clinical events. The sensitivity, specificity, and diagnostic accuracy of CMR are 85%, 93%, and 89%, respectively. The sensitivity, specificity, and diagnostic accuracy of stress SPECT are 84%, 91%, and 88%, respectively. CONCLUSION: Stress CMR has similar diagnostic accuracy as stress SPECT in diagnosis of CAD. PMID- 26268825 TI - Optimizing radionuclide imaging in the assessment of cardiac sarcoidosis. PMID- 26268826 TI - Incidental focal myocardial (18)F-FDG uptake indicating asymptomatic coronary artery disease. PMID- 26268827 TI - Training in nuclear cardiology: What's new? PMID- 26268828 TI - Adsorption of soft particles at fluid interfaces. AB - Soft particles can be better emulsifiers than hard particles because they stretch at fluid interfaces. This deformation can increase adsorption energies by orders of magnitude relative to rigid particles. The deformation of a particle at an interface is governed by a competition of bulk elasticity and surface tension. When particles are partially wet by the two liquids, deformation is localized within a material-dependent distance L from the contact line. At the contact line, the particle morphology is given by a balance of surface tensions. When the particle radius R?L, the particle adopts a lenticular shape identical to that of an adsorbed fluid droplet. Particle deformations can be elastic or plastic, depending on the relative values of the Young modulus, E, and yield stress, sigmap. When surface tensions favour complete spreading of the particles at the interface, plastic deformation can lead to unusual fried-egg morphologies. When deformable particles have surface properties that are very similar to one liquid phase, adsorption can be extremely sensitive to small changes of their affinity for the other liquid phase. These findings have implications for the adsorption of microgel particles at fluid interfaces and the performance of stimuli responsive Pickering emulsions. PMID- 26268829 TI - Health sciences students' perception of the educational environment of KLE University, India as measured with the Dundee Ready Educational Environment Measure (DREEM). AB - This study aimed to evaluate the educational environment of the health sciences programs of KLE University, Belgaum, Karnataka, India, to identify their strengths and weaknesses, and to suggest strategies to improve the educational environment to be on par with global standards. A cross-sectional study was conducted using the Dundee Ready Educational Environment Measure (DREEM) questionnaire, filled out by 914 of the 1,004 students (91.0%) who were majoring in medicine, dentistry, nursing, physiotherapy, and public health. The data were analysed according to the DREEM guidelines. Responses were received from 914 students, of whom 34.03% were men and 65.9% were women. The majority (67.1%) of students were 20-24 years of age. The mean overall DREEM score was 120.21+/-22.4 (maximum, 200) and approached the normal distribution (Lilliefors test, P<0.01). The DREEM scores of each group of students were as follows: dental, 125.0; medical, 122.4; public health, 121.0; physiotherapy, 117.0; and nursing, 116.3. Male students had more positive perceptions than female students (P<0.05), and postgraduate students had more positive perceptions than undergraduate students (P<0.05). The overall DREEM score (120.21) indicates that the educational environment was found to be more positive than negative. PMID- 26268830 TI - Factors that influence the choice to work in rural township health centers among 4,669 clinical medical students from five medical universities in Guangxi, China. AB - PURPOSE: To produce competent undergraduate-level medical doctors for rural township health centers (THCs), the Chinese government mandated that medical colleges in Central and Western China recruit rural-oriented, tuition-waived medical students (RTMSs) starting in 2010. This study aimed to identify and assess factors that influence the choice to work in rural township health centers among both RTMSs and other students from five medical universities in Guangxi, China. METHODS: An internet-based self-administered questionnaire survey was conducted with medical students in Guangxi province. Multinomial logistic regression was used to identify factors related to the attitudes toward work in a rural township health center. RESULTS: Among 4,669 medical students, 1,523 (33%) had a positive attitude and 2,574 (55%) had a neutral attitude toward working in THCs. Demographic characteristics, personal job concerns, and knowledge of THCs were associated with the choice of a career in THCs. The factors related to a positive attitude included the following: three-year program, a rural-oriented medical program, being male, an expectation of working in a county or township, a focus on medical career development, some perceived difficulty of getting a job, having family support, sufficient knowledge of THCs, optimism toward THC development, seeking lower working pressure, and a lower expected monthly salary. CONCLUSION: Male students in a three-year program or a rural-oriented tuition waived medical education program were more likely to work in THCs. Selecting medical students through interviews to identify their family support and intentions to work in THCs would increase recruitment and retention. Establishing favorable policies and financial incentives to improve living conditions and the social status of rural physicians is necessary. PMID- 26268831 TI - Associations of learning style with cultural values and demographics in nursing students in Iran and Malaysia. AB - PURPOSE: The goal of the current study was to identify associations between the learning style of nursing students and their cultural values and demographic characteristics. METHODS: A non-probability purposive sampling method was used to gather data from two populations. All 156 participants were female, Muslim, and full-time degree students. Data were collected from April to June 2010 using two reliable and validated questionnaires: the Learning Style Scales and the Values Survey Module 2008 (VSM 08). A simple linear regression was run for each predictor before conducting multiple linear regression analysis. The forward selection method was used for variable selection. P-values <=0.05 and <=0.1 were considered to indicate significance and marginal significance, respectively. Moreover, multi-group confirmatory factor analysis was performed to determine the invariance of the Farsi and English versions of the VSM 08. RESULTS: The perceptive learning style was found to have a significant negative relationship with the power distance and monumentalism indices of the VSM 08. Moreover, a significant negative association was observed between the solitary learning style and the power distance index. However, no significant association was found between the analytic, competitive, and imaginative learning styles and cultural values (P>0.05). Likewise, no significant associations were observed between learning style, including the perceptive, solitary, analytic, competitive, and imaginative learning styles, and year of study or age (P>0.05). CONCLUSION: Students who reported low values on the power distance and monumentalism indices are more likely to prefer perceptive and solitary learning styles. Within each group of students in our study sample from the same school the year of study and age did not show any significant associations with learning style. PMID- 26268832 TI - An assessment blueprint for the Advanced Medical Life Support two-day prehospital emergency medical services training program in the United States. AB - PURPOSE: Traditional approaches to blueprint creation may focus on fine-grained detail at the expense of important foundational concepts. The purpose of this study was to develop a method for constructing an assessment blueprint to guide the creation of a new post-test for a two-day prehospital emergency medical services training program. METHODS: In order to create the blueprint, we first determined the proportions of the total classroom and home-study minutes associated with the lower- and higher-order cognitive objectives of each chapter of the textbook and the two-day classroom activities during training courses conducted from January to April 2015. These proportions were then applied to a 50 question test structure in order to calculate the number of desired questions by chapter and content type. RESULTS: Our blueprint called for the test to contain an almost even split of lower- and higher-order cognitive questions. One-best answer multiple choice items and extended matching-type items were written to assess lower- and higher-order cognitive content, respectively. CONCLUSION: We report the first known application of an assessment blueprint to a prehospital professional development education program. Our approach to blueprint creation is computationally straightforward and could be easily adopted by a group of instructors with a basic understanding of lower- and higher-order cognitive constructs. By blueprinting at the chapter level, as we have done, item-writers should be more inclined to construct questions that focus on important central themes or procedures. PMID- 26268833 TI - Autophagy: Exploring the anticancer effects of autophagy inhibition. PMID- 26268834 TI - Oesophageal cancer: Model refinement. PMID- 26268835 TI - Epigenetics: Chromatin reorganization on a 'mega' scale. PMID- 26268836 TI - A systematic review of parenting interventions for parents of children with type 1 diabetes. AB - OBJECTIVE: To summarize the parenting intervention literature for parents of children aged 2-10 years (mean age <10 years) with type 1 diabetes and to evaluate intervention efficacy in improving a range of parent, family and child outcomes. The present review de-emphasizes the traditional medical approach to illness management summarized in previous reviews and focuses on parenting factors identified in the literature as important to diabetes management. This review article is important as it outlines the present state of parenting intervention literature for this population. METHODS: Electronic searches were conducted for seven databases (Cumulative index to nursing and allied health literature, MEDLINE, PsycINFO, PubMed, Scopus, The Cochrane library and Web of Science) from their start dates until April 2014. Reference lists of all included papers were also searched for potentially relevant articles. RESULTS: Seven papers, representing six studies, met the inclusion criteria. Three studies primarily focused on improving parenting practices. The intervention programmes described in the remaining studies comprised multiple components; thus, it is difficult to establish the contribution of the parenting components to improving outcomes. CONCLUSIONS: Parenting interventions may help to improve responsibility sharing and cooperation in diabetes management, child behaviour difficulties, parental behaviour, parents' psychological distress and child health outcomes. This review suggests the need for further well-designed trials of parenting interventions to determine their specific contribution to improving outcomes for this population. PMID- 26268837 TI - Arithmetic difficulties in children with mild traumatic brain injury at the subacute stage of recovery. AB - AIM: Arithmetic difficulties have been reported in children with mild traumatic brain injury (mTBI), but the electrophysiological abnormalities underlying these impairments remain unknown. We therefore used event-related potentials (ERPs) to investigate brain functioning during arithmetic in children in the subacute phase after mTBI. METHOD: The participants comprised 16 children with mTBI at the subacute phase of recovery (10 males, mean age 10y 8mo; six females, mean age 10y 8mo) and 16 well-matched comparison children (11 males, mean age 10y 11mo; five females, mean age 10y 6mo). All children were asked to solve single-digit addition problems of small (sum <=10) and large problem size (sum >10) and ERPs were simultaneously recorded. RESULTS: Children with mTBI performed significantly less accurately (mean 81%) than comparison children (mean 91%) on the large (p=0.026) but not on the small problems (p=0.171). We observed no group differences in the early ERP components P1, N1, P2, and N2 (all p values >=0.241), yet significant group differences (p=0.019) emerged for the late positivity component (LPC), which showed smaller mean amplitudes (mean 8.35MUV) in mTBI patients than comparison children (mean 12.95MUV). INTERPRETATION: Immediately after the injury, arithmetic difficulties in children with mTBI are particularly pronounced on more complex arithmetical problems that are less automated. This is reflected in the ERP pattern, with decreased LPC but normal N2 and early ERP components. PMID- 26268838 TI - Two problems and a single solution: Covered stent implantation to close an anterograde pulmonary flow and treat hypoplastic left pulmonary artery after Fontan operation. AB - Several issues may impact on the function of a Fontan circulation including accessory source of pulmonary blood flow and pulmonary artery anatomy. Here we report on a 5.5-year-old boy who showed failing Fontan circulation due to left pulmonary artery stenosis/hypoplasia and significant forward pulmonary blood flow through the native pulmonary artery. Successful implantation of a 34-mm CP covered stent in the left pulmonary artery in a Fontan patient was useful for simultaneous successful treatment of residual antegrade flow from the systemic ventricle to the pulmonary artery and enlargement of hypoplastic left pulmonary artery. (c) 2015 Wiley Periodicals, Inc. PMID- 26268839 TI - An Evidence-Based Systematic Review of Yin Yang Huo (Epimedium spp.) by the Natural Standard Research Collaboration. AB - An evidence-based systematic review of yin yang huo (Epimedium spp.) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing. PMID- 26268840 TI - Hair growth-promotion effects of different alternating current parameter settings are mediated by the activation of Wnt/beta-catenin and MAPK pathway. AB - Electrical stimulation is being used in variable skin therapeutic conditions. There have been clinical studies demonstrating the positive effect of electrical stimuli on hair regrowth. However, the underlying exact mechanism and optimal parameter settings are not clarified yet. To investigate the effects of different parameter settings of electrical stimuli on hair growth by examining changes in human dermal papilla cells (hDPCs) in vitro and by observing molecular changes in animal tissue. In vitro, cultured hDPCs were electrically stimulated with different parameter settings at alternating current (AC). Cell proliferation was measured by MTT assay. The Ki67 expression was measured by immunofluorescence. Hair growth-related gene expressions were measured by RT-PCR. In animal model, different parameter settings of AC were applied to the shaved dorsal skin of rabbit for 8 weeks. Expression of hair-related genes in the skin of rabbit was examined by RT-PCR. At low voltage power (3.5 V) and low frequency (1 or 2 MHz) with AC, in vitro proliferation of hDPCs was successfully induced. A significant increase in Wnt/beta-catenin, Ki67, p-ERK and p-AKT expressions was observed under the aforementioned settings. In animal model, hair regrowth was observed in the entire stimulated areas under individual conditions. Expression of hair related genes in the skin significantly increased on the 6th week of treatment. There are optimal conditions for electrical stimulated hair growth, and they might be different in the cells, animals and human tissues. Electrical stimuli induce mechanisms such as the activation of Wnt/beta-catenin and MAPK pathway in hair follicles. PMID- 26268844 TI - Clustering of lifestyle characteristics and their association with cardio metabolic health: the Lifestyles and Endothelial Dysfunction (EVIDENT) study. AB - Little is known about the clustering patterns of lifestyle behaviours in adult populations. We explored clusters in multiple lifestyle behaviours including physical activity (PA), smoking, alcohol use and eating habits in a sample of adult population. A cross-sectional and multi-centre study was performed with six participating groups distributed throughout Spain. Participants (n 1327) were part of the Lifestyles and Endothelial Dysfunction (EVIDENT) study and were aged between 20 and 80 years. The lifestyle and cardiovascular risk (CVR) factors were analysed using a clustering method based on the HJ-biplot coordinates to understand the variables underlying these groupings. The following three clusters were identified. Cluster 1: unhealthy, 677 subjects (51%), with a slight majority of men (58.7%), who were more sedentary and smokers with higher consumption of whole-fat dairy products, bigger waist circumference as well as higher TAG levels, systolic blood pressure (SBP) and CVR. Cluster 2: healthy/PA, 265 subjects (20%), including 24.0% of males with high PA. Cluster 3: healthy/diet, including 29% of the participants, with a higher consumption of olive oil, fish, fruits, nuts, vegetables and lower alcohol consumption. Using the unhealthy cluster as a reference, and after adjusting for age and sex, the multiple regression analysis showed that belonging to the healthy/PA cluster was associated with a lower waist circumference, body fat percentage, SBP and CVR. In summary, the three clusters were identified according to lifestyles. The 'unhealthy' cluster had the least favourable clinical parameters, the 'healthy/PA' cluster had good HDL-cholesterol levels and low SBP and the 'healthy/diet' cluster had lower LDL-cholesterol levels and clinical blood pressure. PMID- 26268845 TI - Divergent sorting of a balanced ancestral polymorphism underlies the establishment of gene-flow barriers in Capsella. AB - In the Bateson-Dobzhansky-Muller model of genetic incompatibilities post-zygotic gene-flow barriers arise by fixation of novel alleles at interacting loci in separated populations. Many such incompatibilities are polymorphic in plants, implying an important role for genetic drift or balancing selection in their origin and evolution. Here we show that NPR1 and RPP5 loci cause a genetic incompatibility between the incipient species Capsella grandiflora and C. rubella, and the more distantly related C. rubella and C. orientalis. The incompatible RPP5 allele results from a mutation in C. rubella, while the incompatible NPR1 allele is frequent in the ancestral C. grandiflora. Compatible and incompatible NPR1 haplotypes are maintained by balancing selection in C. grandiflora, and were divergently sorted into the derived C. rubella and C. orientalis. Thus, by maintaining differentiated alleles at high frequencies, balancing selection on ancestral polymorphisms can facilitate establishing gene flow barriers between derived populations through lineage sorting of the alternative alleles. PMID- 26268846 TI - Chronic inflammatory demyelinating polyneuropathy (CIDP): change of serum IgG dimer levels during treatment with intravenous immunoglobulins. AB - BACKGROUND: Intravenous immunoglobulin (IVIg) is an effective treatment in chronic inflammatory demyelinating polyneuropathy (CIDP). In most patients, the optimal IVIg dose and regime is unknown. Polyvalent immunoglobulin (Ig) G form idiotypic/anti-idiotypic antibody pairs in serum and IVIg preparations. We determined IgG dimer levels before and after IVIg treatment in CIDP patients with the aim to explore their utility to serve as a surrogate marker for treatment response. METHODS: IgG was purified from serum of five controls without treatment, as well as from serum of 16 CIDP patients, two patients with Miller Fisher syndrome (MFS), and one patient with myasthenia gravis before and after treatment with IVIg. IgG dimer levels were determined by size exclusion chromatography. IgG dimer formation was correlated with clinical response to IVIg treatment in CIDP. Re-monomerized IgG dimer fractions were analyzed for immunoreactivity against peripheral nerve tissue. RESULTS: IgG dimer levels were significantly higher in post- compared to pre-IVIg infusion samples. Low post treatment IgG dimer levels in CIDP patients were associated with clinical worsening during IVIg treatment. Re-monomerized IgG dimer fractions from CIDP patients showed immunoreactivity against peripheral nerve tissue, whereas similarly treated samples from MFS patients showed immunoreactivity against GQ1b. CONCLUSION: Assessment of IgG dimer levels could be a novel approach to monitor CIDP patients during IVIg treatment, but further studies in larger cohorts are warranted to explore their utility to serve as a potential therapeutic biomarker for IVIg treatment response in CIDP. PMID- 26268847 TI - Surgical Versus Nonsurgical Management of Rotator Cuff Tears: Predictors of Treatment Allocation. AB - BACKGROUND: Rotator cuff tears are a common shoulder disorder resulting in significant disability to patients and financial burden on the health care system. While both surgical and nonsurgical management are accepted treatment options, there is a paucity of data to support a treatment algorithm for care providers. Defining variables to guide treatment allocation may be important for patient education and counseling, as well as to deliver the most efficient care plan at the time of presentation. PURPOSE: To identify independent variables at the time of initial clinical presentation that are associated with preferred allocation to surgical versus nonsurgical management for patients with known full thickness rotator cuff tears. STUDY DESIGN: Case control study; Level of evidence, 3. METHODS: A total of 196 consecutive adult patients with known full thickness rotator cuff tears were enrolled into a prospective cohort study. Robust data were collected for each subject at baseline, including age, sex, body mass index (BMI), shoulder activity score, smoking status, size of cuff tear, duration of symptoms, functional comorbidity index, the American Shoulder and Elbow Surgeons (ASES) score, the Western Ontario Rotator Cuff index (WORC), and the Veterans Rand 12-Item Health Survey (VR-12). Logistic regression was performed to identify variables associated with treatment allocation, and the corresponding odds ratios were calculated. RESULTS: Of the 196 patients enrolled, 112 underwent surgical intervention and 84 nonoperative management. With covariates controlled for, significant baseline patient characteristics predictive of eventual allocation to surgical treatment included younger age, lower BMI, and durations of symptoms less than 1 year. Increasing age, higher BMI, and duration of symptoms longer than 1 year were predictive of nonsurgical treatment. Factors that were not associated with treatment allocation included sex, tear size, functional comorbidity score, or any of the patient-derived outcome scores at presentation (ASES, WORC, VR-12, shoulder activity score). CONCLUSION: Patient demographics at the time of initial presentation for a symptomatic rotator cuff tear are more predictive of treatment allocation to a surgical or nonoperative approach than the patient-derived outcome scores for activity level and shoulder disability. Further study is warranted to help define appropriate indications for treatment allocation in patients with rotator cuff tears. PMID- 26268849 TI - New developments in immunotherapies for food allergy. AB - Food allergy affects around 10% of the population. As the prevalence of food allergy continues to increase, disproportionately in children, new therapies for food allergy are being investigated. While there are no approved treatments for food allergy, immunotherapy facilitates significant desensitization and protection from accidental exposure. Nevertheless, current immunotherapies do not entirely nor permanently eliminate sensitivity to the food allergen. Since the rates of sustained unresponsiveness are significantly lower than desensitization, future therapies that enhance the rates of long-term tolerance in patients will catalyze progress in this field over the next 5-10 years. PMID- 26268848 TI - Deep sequencing of the Mexican avocado transcriptome, an ancient angiosperm with a high content of fatty acids. AB - BACKGROUND: Avocado (Persea americana) is an economically important tropical fruit considered to be a good source of fatty acids. Despite its importance, the molecular and cellular characterization of biochemical and developmental processes in avocado is limited due to the lack of transcriptome and genomic information. RESULTS: The transcriptomes of seeds, roots, stems, leaves, aerial buds and flowers were determined using different sequencing platforms. Additionally, the transcriptomes of three different stages of fruit ripening (pre climacteric, climacteric and post-climacteric) were also analyzed. The analysis of the RNAseqatlas presented here reveals strong differences in gene expression patterns between different organs, especially between root and flower, but also reveals similarities among the gene expression patterns in other organs, such as stem, leaves and aerial buds (vegetative organs) or seed and fruit (storage organs). Important regulators, functional categories, and differentially expressed genes involved in avocado fruit ripening were identified. Additionally, to demonstrate the utility of the avocado gene expression atlas, we investigated the expression patterns of genes implicated in fatty acid metabolism and fruit ripening. CONCLUSIONS: A description of transcriptomic changes occurring during fruit ripening was obtained in Mexican avocado, contributing to a dynamic view of the expression patterns of genes involved in fatty acid biosynthesis and the fruit ripening process. PMID- 26268850 TI - Erratum to: Neuroprotection and spatial memory enhancement of four herbal mixture extract in HT22 hippocampal cells and a mouse model of focal cerebral ischemia. PMID- 26268852 TI - Is the A578S Single-Nucleotide Polymorphism in K13-propeller a Marker of Emerging Resistance to Artemisinin Among Plasmodium falciparum in Africa? PMID- 26268853 TI - Risk of Classic Kaposi Sarcoma With Combinations of Killer Immunoglobulin-Like Receptor and Human Leukocyte Antigen Loci: A Population-Based Case-control Study. AB - BACKGROUND: Kaposi sarcoma (KS) is a complication of KS-associated herpesvirus (KSHV) infection. Other oncogenic viral infections and malignancies are associated with certain HLA alleles and their natural killer (NK) cell immunoglobulin-like receptor (KIR) ligands. We tested whether HLA-KIR influences the risk of KSHV infection or KS. METHODS: In population-based case-control studies, we compared HLA class I and KIR gene frequencies in 250 classic (non AIDS) KS cases, 280 KSHV-seropositive controls, and 576 KSHV-seronegative controls composing discovery and validation cohorts. Logistic regression was used to calculate sex- and age-adjusted odds ratios (ORs) and 95% confidence intervals. RESULTS: In both the discovery and validation cohorts, KS was associated with HLA-A*11:01 (adjusted OR for the combined cohorts, 0.4; P = .002) and HLA-C*07:01 (adjusted OR, 1.6; P = .002). Consistent associations across cohorts were also observed with activating KIR3DS1 plus HLA-B Bw4-80I and homozygosity for HLA-C group 1. With KIR3DS1 plus HLA-B Bw4-80I, the KSHV seroprevalence was 40% lower (adjusted OR for the combined cohorts, 0.6; P = .01), but the KS risk was 2-fold higher (adjusted OR, 2.1; P = .002). Similarly, the KSHV seroprevalence was 40% lower (adjusted OR, 0.6; P = .01) but the KS risk 80% higher with HLA-C group 1 homozygosity (adjusted OR, 1.8; P = .005). CONCLUSIONS: KIR-mediated NK cell activation may decrease then risk of KSHV infection but enhance KSHV dissemination and progression to KS if infection occurs. PMID- 26268854 TI - Genes Required for Free Phage Production are Essential for Pseudomonas aeruginosa Chronic Lung Infections. AB - The opportunistic pathogen Pseudomonas aeruginosa causes chronic lung infection in patients with cystic fibrosis. The Liverpool Epidemic Strain LESB58 is highly resistant to antibiotics, transmissible, and associated with increased morbidity and mortality. Its genome contains 6 prophages and 5 genomic islands. We constructed a polymerase chain reaction (PCR)-based signature-tagged mutagenesis library of 9216 LESB58 mutants and screened the mutants in a rat model of chronic lung infection. A total of 162 mutants were identified as defective for in vivo maintenance, with 11 signature-tagged mutagenesis mutants having insertions in prophage and genomic island genes. Many of these mutants showed both diminished virulence and reduced phage production. Transcription profiling by quantitative PCR and RNA-Seq suggested that disruption of these prophages had a widespread trans-acting effect on the transcriptome. This study demonstrates that temperate phages play a pivotal role in the establishment of infection through modulation of bacterial host gene expression. PMID- 26268856 TI - Changes in protein and gene expression of angiotensin II receptors (AT1 and AT2) in aorta of diabetic and hypertensive rats. AB - Diabetes and hypertension have been associated with cardiovascular diseases and stroke. Some reports have related the coexistence of hypertension and diabetes with increase in the risk of developing vascular complications. Recently some studies have shown results suggesting that in the early stages of diabetes and hypertension exist a reduced functional response to vasopressor agents like angiotensin II (Ang II), which plays an important role in blood pressure regulation mechanism through the activation of its AT1 and AT2 receptors. For that reason, the aim of this work was to study the gene and protein expression of AT1 and AT2 receptors in aorta of diabetic SHR and WKY rats. Diabetes was induced by the administration of streptozotocin (60 mg/kg i.p.). After 4 weeks of the onset of diabetes, the protein expression was obtained by western blot and the mRNA expression by RT-PCR. Our results showed that the hypertensive rats have a higher mRNA and protein expression of AT1 receptors than normotensive rats while the AT2 expression remained unchanged. On the other hand, the combination of diabetes and hypertension increased the mRNA and protein expression of AT1 and AT2 receptors significantly. In conclusion, our results suggest that diabetes with hypertension modifies the mRNA and protein expression of AT1 and AT2 receptors. However, the overexpression of AT2 could be associated with the reduction in the response to Ang II in the early stage of diabetes. PMID- 26268855 TI - Incidence and Predictors of Abnormal Anal Cytology Findings Among HIV-Infected Adults Receiving Contemporary Antiretroviral Therapy. AB - BACKGROUND: Anal cancer rates are higher for human immunodeficiency virus (HIV) infected adults than for uninfected adults. Limited published data exist characterizing the incidence of precursor lesions detected by anal cytology. METHODS: The Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy was a prospective cohort of 700 HIV-infected participants in 4 US cities. At baseline and annually thereafter, each participant completed a behavioral questionnaire, and healthcare professionals collected anorectal swabs for cytologic examination and human papillomavirus (HPV) detection and genotyping. RESULTS: Among 243 participants with negative baseline results of anal cytology, 37% developed abnormal cytology findings (incidence rate, 13.9 cases/100 person-years of follow-up; 95% confidence interval [CI], 11.3-16.9) over a median follow-up duration of 2.1 years. Rates among men having sex with men, among women, and among men having sex with women were 17.9 cases/person years of follow-up (95% CI, 13.9-22.7), 9.4 cases/person-years of follow-up (95% CI, 5.6-14.9), and 8.9 cases/person-years of follow-up (95% CI, 4.8-15.6), respectively. In multivariable analysis, the number of persistent high-risk HPV types (adjusted hazard ratio [aHR], 1.17; 95% CI, 1.01-1.36), persistent high risk HPV types except 16 or 18 (aHR, 2.46; 95% CI, 1.31-4.60), and persistent types 16 or 18 (aHR, 3.90; 95% CI, 1.78-8.54) remained associated with incident abnormalities. CONCLUSIONS: The incidence of abnormal anal cytology findings was high and more likely to develop among persons with persistent high-risk HPV. PMID- 26268858 TI - Heartbeat-related EEG amplitude and phase modulations from wakefulness to deep sleep: Interactions with sleep spindles and slow oscillations. AB - Based on physiological models of neurovisceral integration, different studies have shown how cognitive processes modulate heart rate and how the heartbeat, on the other hand, modulates brain activity. We tried to further determine interactions between cardiac and electrical brain activity by means of EEG. We investigated how the heartbeat modulates EEG in 23 healthy controls from wakefulness to deep sleep and showed that frontocentral heartbeat evoked EEG amplitude and phase locking (as measured by intertrial phase locking), at about 300-400 ms after the R peak, decreased with increasing sleep depth with a renewed increase during REM sleep, which underpins the assumption that the heartbeat evoked positivity constitutes an active frontocortical response to the heartbeat. Additionally, we found that individual heart rate was correlated with the frequency of the EEG's spectral peak (i.e., alpha peak frequency during wakefulness). This correlation was strongest during wakefulness and declined linearly with increasing sleep depth. Furthermore, we show that the QRS complex modulates spindle phase possibly related to the correspondence between the frequency of the QRS complex and the spindle frequency of about 12-15 Hz. Finally, during deep sleep stages, a loose temporal coupling between heartbeats and slow oscillation (0.8 Hz) could be observed. These findings indicate that cardiac activity such as heart rate or individual heartbeats can modulate or be modulated by ongoing oscillatory brain activity. PMID- 26268859 TI - [Strengthen the prevention of occupational trichloroethylene health hazards]. AB - Trichloroethylene (TCE) is a widely used organic solvent and an important industrial material. It can be absorbed into the body through respiratory tract and skin, and cause occupational hazards. The acute hazard induced by TCE is occupational medicamentosa-like dermatitis. Epidemiological data showed that long term occupational exposure to TCE could also increase the risk of cancer and cause damage to reproductive system and nervous system. Thus, it is of great significance to strengthen the prevention of occupational TCE health hazards. In this paper, the health hazards and preventive measures of TCE are reviewed. PMID- 26268857 TI - Lack of correlation between the optimal glycaemic control and coronary micro vascular dysfunction in patients with diabetes mellitus: a cross sectional study. AB - BACKGROUND: Coronary microvascular dysfunction (CMD) is associated with cardiovascular events in type 2 diabetes mellitus (T2DM). Optimal glycaemic control does not always preclude future events. We sought to assess the effect of the current target of HBA1c level on the coronary microcirculatory function and identify predictive factors for CMD in T2DM patients. METHODS: We studied 100 patients with T2DM and 214 patients without T2DM. All of them with a history of chest pain, non-obstructive angiograms and a direct assessment of coronary blood flow increase in response to adenosine and acetylcholine coronary infusion, for evaluation of endothelial independent and dependent CMD. Patients with T2DM were categorized as having optimal (HbA1c < 7%) vs. suboptimal (HbA1c >= 7%) glycaemic control at the time of catheterization. RESULTS: Baseline characteristics and coronary endothelial function parameters differed significantly between T2DM patients and control group. The prevalence of endothelial independent CMD (29.8 vs. 39.6%, p = 0.40) and dependent CMD (61.7 vs. 62.2%, p = 1.00) were similar in patients with optimal vs. suboptimal glycaemic control. Age (OR 1.10; CI 95% 1.04 1.18; p < 0.001) and female gender (OR 3.87; CI 95% 1.45-11.4; p < 0.01) were significantly associated with endothelial independent CMD whereas glomerular filtrate (OR 0.97; CI 95% 0.95-0.99; p < 0.05) was significantly associated with endothelial dependent CMD. The optimal glycaemic control was not associated with endothelial independent (OR 0.60, CI 95% 0.23-1.46; p 0.26) or dependent CMD (OR 0.99, CI 95% 0.43-2.24; p = 0.98). CONCLUSIONS: The current target of HBA1c level does not predict a better coronary microcirculatory function in T2DM patients. The appropriate strategy for prevention of CMD in T2DM patients remains to be addressed. PMID- 26268860 TI - [Historical evolution and chinese definition of global health]. AB - Under the background of globalization, public health issues are becoming more and more complicated. In the international arena, global health has gradually replaced international health and "global public health" as one of the dominant terms in the field of public health. However, until now, there is no unified understanding and definition for the concept of global health domestically and internationally. In this article, various foreign experts 'views and domestic experts' opinions about the concept of global health are collected and solicited, in order to generalize appropriate Chinese definition of global health of China. PMID- 26268861 TI - [Health of peacekeepers protection with perspective of global health]. AB - Global health arisen recently, but it developed rapidly and attracted great attention from global researchers and institutions. China, as a member of United Nation, actively participated in many international peacekeeping activities. Health of peacekeepers is global health and it is important to consider and dealt with health of peacekeepers with conception of global health. This article reviewed and analyzed health problems and risk factors faced by peacekeepers,and provided suggestions to strategies to protect health of peacekeepers. PMID- 26268862 TI - [Effect of SET deficiency on the trichloroethylene-induced alteration of DNA methylation in human hepatic L-02 cells]. AB - OBJECTIVE: To compare the DNA methylation-related alteration induced by trichloroethylene (TCE) in human hepatic L-02 cells (L-02 cells) and SET deficient cells, and reveal the role of SET on the mechanisms in TCE-induced epigenetic pathway. METHODS: The L-02 cells and pre-established SET deficient cells were treated with different TCE concentrations, and the changes of total cell viability, DNA methylation level and DNA methyltransferases (DNMTs) activity were measured, respectively. In addition, the TCE-induced alteration in the protein expression of DNMT1, DNMT3a and DNMT3b were analyzed by Western blotting. RESULTS: After treatment with TCE for 24 h, the cell proliferation level was significantly decreased in both cell lines. When concentrations of TCE were 0, 1.0, 2.0, 4.0 and 8.0 mmol/L, the proliferation levels of L-02 cells were 100.00+/-2.70, 83.34+/-2.38, 75.56+/-4.51, 71.67+/-2.77 and 66.67+/-1.63, respectively (F = 58.29, P < 0.001); the cell proliferation levels of SET deficient cells were 101.12+/-1.67, 85.01+/-2.33, 79.44+/-1.67, 78.337+/-3.89 and 76.11+/-3.33, respectively (F = 42.41, P < 0.001). When concentration of TCE reached 4.0 mmol/L, the difference of cell proliferation level between two groups was statistically significant (t = -3.51; P = 0.013). After treated by TCE for 24 h, the global DNA methylation significantly decreased in both cell lines (F value was 212.87 and 79.32, respectively, P < 0.001). The difference between two groups was not statistically significant. After treated by TCE for 24 h, the methyltransferases activities were significantly decreased in both cell cells (F values were 77.92 and 113.80, respectively, P-0.001). The SET deficiency could inhibit the decrease of methyltransferases activity under TCE treatment. When the concentration of TCE reached 8.0 mmol/L, the enzymatic activity of L-02 cells and SET deficient cells decreased to 67.61%+/-2.85% and 72.97%+/- 1.94%, respectively. The difference between two groups was statistically significant (t = -3.94, P = 0.008). After treated with TCE for 24 h, concentrations of TCE were 0, 1.0, 2.0, 4.0 and 8.0 mmol/L, and the relative protein levels of DNMT1 in normal L-02 cells increased significantly to 1.00+/-0.03, 1.28+/-0.04, 1.20+/ 0.04, 1.62+/-0.05, 1.43+/-0.04 (F = 103.00, P < 0.001); In SET deficient cells, the expressions of DNMT1 were 1.00+/-0.04, 0.96+/-0.02, 1.19+/-0.05, 0.85+/-0.03, 0.83+/-0.03, which was significantly down-regulated under TCE treatment (F = 44.18, P < 0.001). CONCLUSION: SET deficiency can significantly attenuate the TCE induced decreases of cell viability and DNMTs activity, as well as alteration of protein expression of DNMT1 in L-02 cells, which indicated that SET was involved in the mechanism of TCE-induced cytotoxicity and epigenetic pathway in L-02 cells. PMID- 26268863 TI - [Investigation of trichloroethylene-induced effects on subcellular proteomes in L 02 hepatic cells]. AB - OBJECTIVE: To put the insight into the trichloroethylene (TCE)-induced effect on the differential expression of subcellular proteins in human normal liver cell line (L-02). METHODS: The membrane proteins and nuclear proteins of TCE-treated (8.0 mmol/L) group and controls were extracted by subcellular proteome extraction kit, respectively. The TCE-induced differentially expressions were analyzed by a two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and matrix assisted laser desorption/ionization tandem time-of-flight spectrometry (MALDI TOF-MS). Bioinformatics analysis was used to reveal the biological processes and predict transmembrane domains of differential expressed proteins. The expression of ATP synthase subunit beta (ATP5B), heterogeneous nuclear ribonucleoprotein H2 (hnRNP H2) and far up steam element-binding protein 1 (FUBP1) were measured under TCE treatment by Western blot. RESULTS: After TCE treatment for 24 h in L-02 cells, 14 membrane proteins and 18 nuclear proteins were identified as differential expression. After treated with TCE in concentrations of 0, 2.0, 4.0 and 8.0 mmol/L for 24 h, the relative levels of ATP5B expression were 1.00+/ 0.03, 1.21+/-0.14, 1.25+/-0.12 and 1.48+/-0.17 (F = 8.51, P = 0.007), the relative levels of hnRNP H2 expression were 1.00+/-0.09, 1.22+/-0.15, 1.43+/ 0.21, 1.53+/-0.17 (F = 6.57, P = 0.015), respectively; the relative levels of FUBP1 expression were 1.00+/-0.11, 0.91+/-0.07, 0.73+/-0.04 and 0.67+/-0.03 (F = 15.81, P = 0.001), respectively, which were consistent with the results in proteomics. The bioinformatics analysis showed that the most dominant biological process were involved in RNA processing (10 proteins, P = 2.46*10(-6)), especially in RNA splicing (9 proteins, P = 1.77*10(-7)). CONCLUSION: The exposure of TCE could alter the expression of membrane proteins and nuclear proteins in L-02 cells. These abnormal expressed proteins involved in RNA splicing would provide novel clues for further understanding of TCE-induced hepatotoxicity. PMID- 26268864 TI - [Dietary intake and risk assessment of diethylhexyl phthalate in Chinese populations]. AB - OBJECTIVE: To assess dietary exposure of diethylhexyl phthalate(DEHP) among Chinese population, including general population, children aged 2-6 years, adolescent aged 7-12, young people aged 13-17, adults aged 18-59 years old as well as older people aged 60 and above and its health risk. METHODS: A total of 6 650 food samples were collected during 2011 to 2013 from 140 local markets of 14 provinces in China, which covered major foods in China. Samples were detected by GC-MS and categorized into 22 food groups. Food consumption data were taken from China National Nutrition and Health Survey performed in 2002 including 68 959 subjects. Mean concentrations of DEHP in food were combined with individual food consumption data to estimate dietary exposure, and food contributors to dietary DEHP intake were also calculated. Then, the exposure was compared with the tolerable daily intake (TDI, 50 ug.kg(-1)-d(-1)) of DEHP. RESULTS: DEHP level in foods (n = 6 650) was in the range of not detected to 43.80 mg/kg. Mean dietary intakes of DEHP in general population was 2.07 (95% CI: 0.06-4.09) ug.kg(-1).d( 1), accounting for 4.14 percent of TDI (50 ug.kg(-1).d(-1)). Mean dietary intake for population aged 2-6, 7-12, 13-17, 18-59 as well as elderly aged 60 and above were 3.92 (95% CI: 0.83-7.01), 3.02 (95% CI: 0.69-5.36), 2.17 (95% CI: 0.54 3.81), 1.83 (95% CI: 0.46-3.21) and 1.66 (95% CI: 0.38-2.94) ug.kg(-1).d(-1) respectively. The 97.5 percentile intakes in the general populations was 4.73 ug.kg(-1).d(-1), accounting for 9.46% of TDI. Main food sources of DEHP were rice (28.4% (0.59/2.07)), melon solanaceous vegetables (14.7% (0.30/2.07)) and flour (13.2% (0.27/2.07)) for the general population. CONCLUSION: The results suggested that dietary exposure to DEHP among Chinese population was lower than tolerable daily intake of DEHP and there were no health concerns based on generally accepted exposure limits. Rice, melon solanaceous vegetables and flour were main food contributors of DEHP dietary intake for Chinese populations. PMID- 26268865 TI - [Probabilistic assessment of dietary exposure to both deoxynivalenol and zearalenone from cereal-based products in Chinese populations]. AB - OBJECTIVE: To elucidate the dietary exposure to deoxynivalenol (DON) and zearalenone (ZEN) from cereal-based products in Chinese populations using the probabilistic assessment approach. METHODS: A total of 292 wheat flours and 347 corn-based products were collected from sampling sites of 107 supermarkets or farmers markets, which were randomly selected from 44 cities of 13 provinces in 2009 by the stratified cluster random sampling method. Then, DON and ZEN contamination levels in these samples above analyzed by UPLC-MS/MS in combination with the food consumption data of 68 959 respondents, who were divided into group 1 aged 3 to 13 years old, and group 2 aged 14 and over 14 years old (>=14 years old), obtained by China National Nutrition and Health Survey in 2002 were investigated. A probabilistic assessment model using Monte Carlo simulation was applied to derive the intake distribution of P(1)-P(99) percentile of dietary exposure to DON and ZEN. Meanwhile, all parameters related to dietary exposure to both toxins were compared with either the provisional maximum tolerable daily intake (PMTDI) of 1 ug.kg(-1).d(-1) for DON, or the tolerable daily intake (TDI) of 0.25 ug.kg(-1).d(-1) for ZEN in order to evaluate the risk of dietary intake of two toxins and find the minimum percentile of dietary exposure to these two toxins. The statistical differences of dietary exposure to these two toxins between two groups were achieved by t test. RESULTS: The detection frequencies of DON in wheat flours and corn-based products were 100% (292/292) and 97.4% (338/347), respectively. A total of 21 out of 639 samples (wheat flours: 5/292, corn-based products: 16/347) were positive for DON at the levels exceeding the Chinese regulatory limit of 1 000 ug/kg for DON. And the detection frequencies of ZEN in wheat flours and corn-based products were 53.4% (156/292) and 87.6% (304/347), respectively.54 out of 347 corn-based products and no wheat flours were positive for ZEN at the levels exceeding the Chinese regulatory limit of 60 ug/kg for ZEN. Meanwhile, the mean values (95% CI) of the P(50), P(75), P(90), P(95), P(97.5) and P(99) percentile of dietary exposure to DON in populations of 3 to 13 years old were 0.170 (0.170-0.171), 0.762 (0.759-0.765), 2.066 (2.038 2.069), 3.515 (3.501-3.530), 5.342 (5.314-5.372), and 9.220 (9.155-9.279) ug . kg(-1).d(-1), which were higher than those in populations of >=14 years old (0.131 (0.130-0.131), 0.500 (0.498-0.501), 1.280 (1.276-1.285), 2.138 (2.128 2.14), 3.510 (3.494-3.527), and 5.512 (5.474-5.546) ug.kg(-1).d(-1)), with t values of 87.19, 163.87, 164.66, 157.78, 105.47 and 96.31, and all P values less than 0.001. And the mean values (95% CI) of the P(50), P(75), P(90), P(95), P(97.5) and P(99) percentile of dietary exposure to ZEN in populations of 3 to 13 years old were 0.001 (0.001-0.001), 0.006 (0.006-0.006), 0.039 (0.038-0.039), 0.101 (0.100-0.101), 0.195 (0.194-0.197) and 0.378 (0.374-0.381) ug . kg(-1).d( 1), which were also higher than those in populations of >=14 years old (0.001 (0.001-0.001), 0.004 (0.004-0.004), 0.026 (0.026-0.026), 0.061 (0.060-0.061), 0.115 (0.115-0.116) and 0.232 (0.231-0.235) ug.kg(-1).d(-1)) with T-values of 151.11, 73.80, 96.81, 100.81, 91.93 and 76.13, and all P values less than 0.001. Besides, the minimum percentile of dietary exposure to DON in populations of 3 to 13 years old and >=14 years old exceeded the corresponding PMTDI of 1 ug.kg( 1).d(-1) was found in the probability distribution of P(76) (99% percentile = 1.03 ug.kg(-1).d(-1)) and P(84) (95% percentile = 1.01 ug.kg(-1).d(-1)) percentile, respectively. And the minimum percentile of dietary exposure to ZEN in populations of 3 to 13 years old and >=14 years old exceeded the corresponding TDI of 0.25 ug.kg(-1).d(-1) was found in the probability distribution of P(97) (95% percentile = 0.25 ug.kg(-1).d(-1)) and P(98) (90% percentile = 0.26 ug.kg( 1).d(-1)) percentile, respectively. CONCLUSION: The contamination levels of DON and ZEN in wheat flours and corn-based products and the risk of dietary exposure to both DON and ZEN in populations in Chinese populations were at relatively low levels. The dietary exposure to both DON and ZEN in populations of 3 to 13 years old was higher than those in populations of >=14 years old . Populations of 3 to 13 years old were the populations at the high risk of dietary exposure to both mycotoxins. PMID- 26268866 TI - [Effects on cell proliferation capacity and genome stability in periphery lymphocytes of occupational diesel exhaust exposed workers]. AB - OBJECTIVE: To investigate the cell proliferation and genome stability in workers with occupational exposure to diesel exhaust (DE). METHODS: In 2012, 117 DE exposed workers and 106 control workers were recruited by cluster sampling in this study. The demographic data were obtained by questionnaire survey. The airborne fine particle and enriched polycyclic aromatic hydrocarbons (PAHs) at different workplaces were collected and analyzed. The concentrations of main PAHs monohydroxy metabolites in the urine were determined by high performance liquid chromatography-mass spectrometry (LC-MS), which could reflect the internal exposure level of DE. The cell proliferation capacity and genome stability in the periphery lymphocytes of workers were evaluated by cytokinesis-block micronucleus (CBMN) cytome assay. RESULTS: The concentrations (median (P5-P95)) of total PAHs monohydroxy metabolites in the urine of exposed group and control group were 12.96 (4.73-28.10), 4.76 (0.90-15.00) ug/L, respectively, and the exposed group was higher than that of controls (Z = -8.77, P < 0.001). The nuclear division index (NDI) of exposed group and control group was 1.68+/-0.13, 1.85+/-0.16, respectively, and the NDI of exposed group showed significantly decreased (t = 8.86, P < 0.001), while the genome instability index calculated by micronucleus, nuclear bridges and nuclear buds, of exposed group and control group was 13.27+/ 6.26, 4.83+/-3.38, respectively, and the exposed group had statistically significant increase (Z = -10.08, P < 0.001). The tertiles of total PAHs monohydroxy metabolites in the urine were categorized into low, medium and high groups (<5.96, 5.96-12.46, >12.46 ug/L). With the NDI decreased, 1.81+/-0.17, 1.79+/-0.17, 1.68+/-0.14 (F = 13.14, P < 0.001), genome instability index began to increase 5.80+/-4.15, 9.97+/-7.14, 11.99+/-6.61 (/1 000), respectively (chi(2) = 36.74, P < 0.001). With the increase of total PAHs monohydroxy metabolites level in corresponding groups. In addition, the NDI was negatively correlated with the frequencies of micronucleus, nuclear bridges, nuclear buds and genome instability index, respectively, and the difference was statistically significant (P < 0.001). CONCLUSIONS: DE exposure lead to inhibition of cell proliferation capacity and increase genome instability in the peripheral lymphocytes of occupational-exposed population, providing important clues and evidence for early biomarkers monitoring. PMID- 26268867 TI - [The infection and molecular characteristics of Vibrio parahaemolyticus isolated from intestinal outpatient in two sentinel hospitals in Shanghai, 2010-2012]. AB - OBJECTIVE: To analyze virulence genes and molecular characteristics of Vibrio parahaemolyticus isolated from sporadic cases with diarrhea in tow sentinel hospitals of Shanghai, 2010-2012. METHODS: A total of 2 729 stool samples were collected from two surveillance sentinel hospitals in Shanghai 2010-2012. Vibrio parahaemolyticus strains were isolated and identified from diarrhea out patients using TCBS agar plates and biochemical reactions. Thermostable direct hemolysingene (tdh), thermostable-related hemolysin gene (trh), hemolysin gene (tlh) were detected by multiplex PCR method. Isolates were analyzed by PFGE and MLST. The PFGE profiles were analyzed using BioNumerics software. RESULTS: A total of 30 clinical Vibrio parahaemolyticus strains isolated from 2 729 stool samples. The anually Vibrio parahaemolyticus isolation rate during 2010 to 2012 were 1.1%(11/973), 1.0%(11/1 120) and 1.3%(8/636) respectively. The PCR positive rates of virulence genes tlh, tdh and trh were 100%, 97% and 0 respectively. The Vibrio parahaemolyticus strains were divided into 13 PFGE types (P1-P13)and 3 ST types (ST-189, ST-799, ST-3). Among 13 PFGE types, P4 was the main PFGE type, accounting for 30%(9/30). P9, P10 were accounting for 12% (4/30) respectively, P1, P2, P12, P13 were accounting for 7%(2/30) respectively, the others types were 3%(1/30) respectively. MLST analysis results showed there are three ST types, ST3 was 84%(25/30), ST189 and ST799 were accounting for 13% (4/30) and 3% (1/30) respectively. CONCLUSION: The infection rate of Vibrio parahaemolyticus was not very high from 2010-2012 in Shanghai, all strains were positive for tlh and negative for trh. ST3 was the major type of Vibrio parahaemolyticus. PMID- 26268868 TI - [Acceptance and influence factor of central slaughtering of live poultry in residents of Guangzhou]. AB - OBJECTIVES: To investigate a survey about acceptance of central slaughtering of live poultry in residents of Guangzhou. METHODS: We conducted a telephone survey by sampling residents with fixed-line telephone and with normal hearing, whose age is more than 15 years, by Mitofsky-Waksberg two-stage method during Jan 6(th) to 8(th), 2014. 358 residents finished the telephone questionnaire by 12 320 health hot line. We investigated the acceptance rate of city-wide central slaughtering permanently. We compared the difference between the respondents and the 2010 Guangzhou census data by Cohen's effect sizes (w) and weighted by population age and sex. We used chi(2) test to compare the acceptance rate of central slaughtering in residents with different characteristic. We used multiple logistic regression analysis to analyze the factors. RESULTS: The difference in gender and age was small between respondents and the 2010 Guangzhou census data (w value was 0.13, 0.28, respectively), but that in education and marital status was large (w value was 0.52, 0.31, respectively). 49.0% (95% CI: 43.7%-54.3%) accept city-wide central slaughtering permanently. The acceptance rate of city wide central slaughtering permanently in those who bought fresh, chilled and frozen poultry in their family in previous year was 54.3% (133/245), 60.0% (57/95) and 59.8% (49/82), respectively. It was more than those who didn't buy fresh, chilled and frozen poultry (38.1% (43/113), 44.9% (118/263) and 45.7% (126/276); chi(2) values were 8.15, 6.40 and 5.03; P values were 0.004, 0.011 and 0.025, respectively). The acceptance rate of city-wide central slaughtering permanently in those who deem fresh poultry taste better than live poultry was 64.9% (24/38). It more than those who deem not (47.0%, 151/320) (chi(2) = 4.22, 6.02, P = 0.040, 0.014, respectively). The acceptance rate of city-wide central slaughtering permanently in the male (OR = 2.68, 95% CI: 1.64-4.37) and those who deem getting sick due to buying live birds from LPM (OR = 1.72, 95% CI: 1.05 2.82), who can accept only fresh poultry carcass supply (OR = 2.39, 95% CI: 1.33 4.30), Who bought live poultry in their family in previous year (OR = 0.29, 95% CI: 0.11-0.74), who will decrease the consumption after ban on live poultry sale (OR = 0.50, 95% CI: 0.30-0.83) was 58.6% (109/186), 59.0% (92/156), 60.7% (139/230), 44.9% (132/295), 36.6% (68/186), respectively. CONCLUSION: In the early stage of avian influenza A(H7N9) epidemic in Guangzhou, the rate of acceptance of central slaughtering permanently in residents was not so high. Who deem getting sick due to buying live birds from LPM, who could accept only fresh poultry carcass supply and the male more accept city-wide central slaughtering permanently. PMID- 26268869 TI - [The association between smoking status and carotid artery plaque in rural areas of Eastern part of China]. AB - OBJECTIVE: To investigate the correlation between smoking status and carotid plaque in rural population residing in Eastern part of China. METHODS: Between July and September of 2013, an epidemiological survey was carried out in residents aged 40 or above men who were enrolled randomly in rural areas of Anqing, Anhui province and Lianyungang, Jiangsu province. The data on epidemiological characteristics including smoking status, physical examination were collected using standardized protocol, and carotid ultrasonography was applied to examine the incidence of carotid plaque among never smokers, former smokers and current smokers. Logistic regress analysis was performed to determine the effect of smoking on carotid plaque. RESULTS: In the study, a total of 625 male participants were included in the study. 51.4% (321 cases) were current smokers, 21.3% (133 cases) were former smokers, and 27.4% (171 cases) were never smokers. 32.0% (200/625) had carotid plaque. The incidence of carotid plaques was significantly higher in current smokers (35.2%, 113/321) than that in never smokers(23.4%,40/171) (chi(2) = 7.26, P = 0.007) and the incidence in former smokers (35.3%, 47/133) was also higher than that in never smokers (23.4%, 40/171) (chi(2) = 5.23, P = 0.022). Multiple logistic regression analysis showed that current cigarette smoking is significantly associated with the increased risk of carotid plaque (OR = 1.84, 95% CI: 1.13-2.98, P = 0.014) in comparison with never smokers, and there was an interaction between current smoking and age in association with carotid plaque. Compared with the young (<=60 years old) and never smoking group (8%, 3/40), prevalence of carotid plaque among the elderly (>70 years old) and smoking group (55%, 31/56) was significantly higher (OR = 8.06, 95% CI: 2.07-31.45) after adjusting for age, systolic blood pressure, diastolic blood pressure, blood glucose, total cholesterol, triglyceride high density lipoprotein, body mass index, drinking and regional differences. CONCLUSION: It found that cigarette smoking was associated with increased risk of carotid plaque in rural elderly population residing in Eastern part of China. PMID- 26268871 TI - [A nested case-control study on the relationship of three kinds of cytokines and risk of cardio-cerebrovascular events among Inner Mongolians]. AB - OBJECTIVE: To investigate the relationship between homocysteine (Hcy), von willebrand factor (vWF), soluble intercellular adhesion molecule-1 (sICAM-1) and the risk of cardio-cerebrovascular events among Inner Mongolians. METHODS: A survey was conducted among 2 589 Inner Mongolians from May 2002 to June 2003, and they were followed up for about ten years. The 182 individuals who developed cardio-cerebrovascular events in the cohort were defined as cases and those whose age, gender and residence 1:1 matched to cases were selected from the individuals who did not developed cardio-cerebrovascular events as controls. Then, a nested case-control study was used to analyze the relationship between Hcy, vWF and sICAM-1 and risk of cardio-cerebrovascular events. Conditonallogistic regression analysis was used to calculate OR values and 95% CI. RESULTS: The cases had a higher baseline blood pressure, higher prevalence of hypertension and family history of hypertension compared to controls (all P values < 0.05), however, there were no significantly different between TC, TG, LDL-C, HDL-C, FBG, smoking and drinking rates (all P values > 0.05). The M (P(25)-P(75)) of Hcy were 10.68 (7.84-14.98) and 10.02 (6.64-13.94) umol/L, vWFs were 10.88 (8.14-14.58) and 10.42 (7.97-13.50) mg/L, sICAM-1 were 336.48 (260.68-409.87) and 335.12 (269.87 409.87) ng/ml. They were not significantly different between the two groups (Z values were 0.89, 0.94 and 0.29, respectively, all P values >0.05). After adjustment for the family history of hypertension, hypertension, TC, FPG, BMI, smoking and drinking rate, the conditional logistic regression showed that OR (95% CI) of risk of cardio-cerebrovascular events were 1.00 (0.52-1.93), 2.37 (1.25-4.49), and 0.81 (0.45-1.47) for the participants with increased Hcy, vWF, and sICAM-1, compared with those with normal Hcy, vWF, and sICAM-1, respectively. CONCLUSION: In the Inner Mongolians, increased vWF at baseline may increase the risk of cardio-cerebrovascular events, and increased Hcy and sICAM-1 were not significantly associated with the risk of cardio-cerebrovascular events. PMID- 26268870 TI - [Correlation between the expression level of coiled-coil domain-containing protein 80 and obesity]. AB - OBJECTIVE: To explore the relationship between expression of coiled-coil domain containing protein 80(CCDC80) and obesity in serum and adipose tissues. METHODS: A cross-sectional survey was conducted in a hospital in Tangshan in September 2010. 100 people including 78 healthy people and 22 with type-2 diabetes were recruited. Another 36 female patients with benign tumor of Obstetrics and Gynecology were also recruited. Demographic characteristics and serum samples were collected from all subjects, basic biochemical indicators were tested. All subjects were divided into 'Normal Weight' and 'Overweight and Obese' according to their BMI (BMI <24.0 kg/m(2); BMI>=24 kg/m(2)). Serum CCDC80 of the 100 subjects was detected by ELISA. Visceral and subcutaneous fat were derived from the other 36 female subjects, and Real-time PCR was used to detect CCDC80 mRNA expression in adipose tissues. Pearson correlation and multiple linear regression were used to analyze the correlation between serum or adipose CCDC80 expression and waist, BMI, and other biochemical indicators. RESULTS: The age of 100 subjects was (52.9+/-8.4) years old. 44% of them were women (44 cases) and 56% of them were men (56 cases). After dividing them into three groups according to their BMI, covariance analysis were conducted, and age and gender were adjusted. The HDL-C level was significantly different among three groups (F = 10.73, P < 0.001): 'Overweight and obese combined with diabetes' group ((0.90+/-0.06) mmol/L)< 'Overweight and obese' group ((1.14+/-0.04) mmol/L) < 'Normal weight' group ((1.28+/-0.05) mmol/L). The adjusted expression of serum CCDC80 of the 100 subjects was (5.84+/-0.16) pg/ml, (5.81+/-0.98) pg/ml among men and (5.97+/-0.89) pg/ml among women, and there was no significant difference (t = -0.812, P = 0.419) between genders. ANOVA revealed that there was no significant differences of the expression of serum CCDC80 among three groups (F = 1.06, P = 0.351), 'Normal weight' group was (5.84+/-0.16) pg/ml, 'overweight and obese' group was (6.11+/-0.14) pg/ml, and 'Overweight and obese combined with diabetes' group was (5.84+/-0.19) pg/ml. The analysis showed that FBG had a negative correlation with serum CCDC80 (R(b) = -0.223, P = 0.026). Multivariate linear regression had a similar result, with 1 mmol/L increase of serum FBG, serum CCDC80 decreases for 0.24 pg/ml (beta = -0.24, 95% CI: -0.21--0.02). There was also a negative correlation between serum CCDC80 and FBG in overweight and obese people (R(a) = 0.368, P = 0.013). Besides, CCDC80 mRNA was detected in both subcutaneous and visceral adipose tissue of 36 cases, the expression level was 0.06+/-0.02 for subcutaneous fat, was 0.05+/-0.04 for visceral fat, and the expression in visceral fat was lower (0.05+/-0.03) than that in subcutaneous fat (0.06+/-0.03) (t = 2.50, P = 0.025) among overweight and obese group. There was a negative correlation between waist and visceral CCDC80 mRNA expression (r = -0.472, P = 0.035). CONCLUSION: This study suggested that CCDC80 may be involved in energy and insulin metabolism, and plays a protective role in obesity and diabetes. PMID- 26268872 TI - [Association and interaction between 10 SNP of peroxisome proliferator-activated receptor and non-HDL-C]. AB - OBJECTIVE: To examine the main effect of 10 Peroxisome proliferators-activated receptor (PPAR) SNP in contribution to non-HDL-C and study whether there is an interaction in the 10 SNPs. METHODS: Participants were recruited within the framework of the PMMJS (Prevention of Multiple Metabolic Disorders and Metabolic Syndrome in Jiangsu province) cohort-population-survey, which was initiated from April 1999 to June 2004, and 5-year follow-up data from total 4 582 subjects were obtained between March 2006 and October 2007. A total of 4 083 participants received follow-up examination. After excluding subjects who had experienced stroke or exhibited cardiovascular disease, type 2 diabetes or a BMI <18.5 kg/m(2), a total of 820 unrelated individual subjects were selected from 3 731 subjects on October of 2009. Blood samples which were collected at the baseline were subjected to PPARalpha, PPARdelta and PPARgamma 10 SNPs genotype analysis. Logistic regression model was used to examine the association between 10 SNPs in the PPARs and non-HDL-C. Interactions within the 10 SNP were explored by using the Generalized Multifactor Dimensionality Reduction (GMDR). RESULTS: A total of 820 participants (mean age was 50.05+/-9.41) were included in the study and 270 were males and 550 were females. Single-locus analysis showed that after adjusting gender, age, smoking, alcohol consumption, physical activity, high-fat diet and low-fiber diet factors, rs1800206-V and rs3856806-T were significantly associated with higher non-HDL-C levels. V allele (LV + VV genotype) carriers of rs1800206 have a average non-HDL-C levels on (3.15 +/- 0.89)mg/L (F = 15.01, P = 0.002); T allele (CT+TT genotype) carriers of rs3856806 have a average non-HDL-C levels on (3.03+/-1.01) mg/L (F = 9.87, P = 0.005). GMDR model analysis showed that after adjusting the same factors, two-locus model, five-locus model, six locus model and seven-order interaction models were all statistically significant (P<0.05), and the seven-locus model (rs1800206, rs3856806, rs135539, rs4253778, rs2016520, rs1805192, rs709158) was the best model (P = 0.001), the cross validation consistency was 10/10 and testing accuracy was 0.656. CONCLUSION: Rs1800206 and rs3856806 were significantly associated with non-HDL-C. And there was an gene-gene interaction among rs1800206, rs3856806, rs1800206, rs135539, rs4253778, rs2016520, rs1805192, rs3856806 and rs709158 which could influence the non-HDL-C levels. PMID- 26268873 TI - [Analysis of the incidence and perinatal outcomes of multiple births in Zhejiang Province from 2008 to 2013]. AB - OBJECTIVE: To analyze the trends of multiple births rates and their perinatal outcomes in Zhejiang province from 2008 to 2013. METHODS: Data were obtained from hospital-based perinatal mortality surveillance system in Zhejiang, including all the hospitals in 30 monitoring counties (districts). All births (28 or more weeks of gestation) born in the monitoring hospitals were included in our study within 7 days after delivery from 2008 to 2013. Chi-square test was performed for statistical analyses for comparisons between regions. Trends in the incidence of multiple births and causes of perinatal death were analyzed using chi-square test for trend. RESULTS: From 2008 to 2013, the multiple births rate in Zhejiang province was increased and the rates were 2.32% (5 551/239 636), 2.49% (6 053/243 452), 2.61% (6 549/250 594), 2.82% (7 758/275 105), 2.91% (8 803/302 447) and 3.06% (9 051/295 709), respectively. And the perinatal mortality rates for multiple births were 4.32% (240/5 551), 3.45% (209/6 053), 3.76% (246/6 549), 2.86% (222/7 758), 2.77% (244/8 803) and 2.11% (191/9 051), respectively. A significant drop in the perinatal mortality rates for multiple births was observed between 2008 and 2013 (chi(2) trend = 66.52, P < 0.001). There was a significantly greater risk for perinatal death to multiple births when compared with single birth (OR = 3.62, 95% CI: 3.42-3.83). The three leading causes of perinatal death for multiple births were birth defect, premature and/or low birth weight, and twin-twin transfusion syndrome. CONCLUSION: The multiple births rates in Zhejiang province showed an increasing trend. The perinatal mortality rates for multiple births were decreased annually, however, it was still higher than those in developed countries. PMID- 26268874 TI - [Effect of CCM3 gene defect on lead-induced cell genotoxicity in mouse embryonic fibroblasts]. AB - OBJECTIVE: To investigate the effect of CCM3 gene defection on lead induced cell genotoxicity in mouse embryonic fibroblasts. METHODS: C57 female mice were mated with CCM3 gene heterozygous male mice. E13.5 embryos were taken to isolate primary mouse embryonic fibroblasts. After genotyping, wild type and heterozygous cells were treated with different doses of lead acetate. Cell viability, genotoxicity and protein expression were detected by MTS assay, CB micronucleus method and Western blot, respectively. RESULTS: Mouse embryonic fibroblasts with lead acetate treatment for 24 h, wild-type cells 100.00 umol/L lead acetate treated group (69.16+/-1.36) and the control group (100.00+/-2.33) compared to cells decreased by 30%, CCM3 heterozygous type cell 100.00 umol/L lead acetate treated group (87.16+/-5.50) and the control group (100.00+/-2.06) compared to cells decreased by 13%, the difference was statistically significant (F values were 98.59, 82.63, P<0.001). Lead acetate treatment after 48 h, wild-type cells 100.00 umol/L lead acetate-treated group (51.99+/-5.62) and the control group (100.00+/-3.11) compared to cells decreased by 50%, heterozygous type cells 100.00 umol/L lead acetate treatment group (66.33+/-4.06) and the control group (100.00+/-5.72) compared to cells decreased by 35%, the differences were statistically significant (F values were 82.63, 36.86, P < 0.001). The results of CBMN test showed that with increased dose, micronucleus cell rate of two genotypes showed an increasing trend, in the wild-type cells, the micronucleus cell rate (/1 000) for the control group, 29.6+/-2.2, 6.25 umol/L dose group 47.3+/-6.6, 25 umol/L dose group 55.5+/-9.1, 100.00 umol/L dose group 66.8+/-3.5; heterozygous cells micronucleus cell rate (/1 000) for the control group, 35.3+/ 5.6, 6.25 umol/L dose of 50.0+/-8.3, 25.00 umol/L dose group 57.0+/-8.5, 100.00 umol/L dose group 58.8+/-2.1. Micronucleus cell rates (/1 000) were significant differences, in 100.00 umol/L dose groups of two genotypes. Western blot results showed that wild-type cells CCM3 expression 100.00 umol/L lead acetate-treated group (0.70+/-0.03) was 1.32 times higher than the control group (0.53+/-0.07), heterozygous cells CCM3 expression 100.00 umol/L lead acetate-treated group (0.48+/-0.02) was 1.77 times higher than control group that of 0.27+/-0.04, there was statistically significant difference (F values were 14.77, 25.74, P < 0.001); wild-type cells gamma-H2AX expression 100.00 umol/L lead acetate-treated group (0.69+/-0.03) was 1.06 times higher than the control group (0.65+/-0.07), heterozygous cells gamma-H2AX expression 100.00 umol/L lead acetate-treated group (0.99+/-0.04) was 1.55 times higher than the control group CCM3 expression levels (0.64+/-0.06), there was statistically significant difference (wild-type cells: F = 7.08, P = 0.012, heterozygous type cell: F = 13.49, P = 0.002). CONCLUSION: CCM3 gene may play a role in lead-induced genetic toxicity of mouse embryonic fibroblasts, CCM3 gene-lead interactions effects on mouse embryonic fibroblasts cell toxicity. PMID- 26268875 TI - [The changes of gene expression of iron transporters for duodenal iron uptake and export in diet-induced obese mice]. AB - OBJECTIVE: This study aims to determine the gene expression changes of iron transporters-divalent metal transporter 1 (DMT1) and ferroportin 1 (Fpn1) in the duodenal tissue of diet-induced obese mice. METHODS: C57BL/6J mice were randomly divided into normal control (NC) and obesity model (OM) group, 6 in each, and fed on conventional and high-fat diet respectively for 14 weeks by table of random number. Then the DMT1 and Fpn1 mRNA contents in duodenal tissues of the animals were measured by Real-time PCR method, and the protein expression levels were analyzed by Western blot test. RESULTS: The Real-time PCR detection results showed that, compared with the NC group for which the mRNA expression level was defined as 1.0, the Fpn1 mRNA expression in OM group (0.58+/-0.11) was reduced significantly (t = 6.71, P = 0.014), whereas the relative expression level of DMT1 mRNA in OM group (0.89+/-0.26) showed no obvious alteration (t = 2.01, P = 0.122). Western blot results showed that the relative protein expression levels of Fpn1 in OM and NC group were 0.32+/-0.06 and 0.65+/-0.19, respectively, and the difference was statistically significant (t = 5.37, P = 0.026). The DMT1 protein relative abundance was 0.88+/-0.21 in OM group and 0.92+/-0.17 in NC group, and the difference has no statistical significance (t = 1.84, P = 0.185). CONCLUSION: Fpn1 gene expression is inhibited in the duodenum of diet-induced obesity mouse while DMT1 expression keeps unchanged, and this implies that decreased iron export from enterocytes into circulation might be responsible for the impaired iron absorption in obesity. PMID- 26268876 TI - [Analysis and study of the relationship between indoor and outdoor air pollution PM2.5 in Chaoyang District of Beijing]. PMID- 26268877 TI - [The detection of enterovirus D68 from the specimen of a severe pneumonia case in Beijing]. PMID- 26268878 TI - [Research progress in carcinogenicity of trichloroethylene and its metabolites]. AB - Trichlorethylene (TCE) is a widely used organic solvent and an important industrial material. It's easily released into the environment through manufacture, use and disposal process, so there is a wide range of occupationally and environmentally exposed population. Based on accumulated research data, International Agency for Research on Cancer (IARC) increased the carcinogenic rating of TCE from probable human carcinogen to certain human carcinogen in 2012. This paper is a review of the carcinogenic effects of TCE and its metabolites from the aspects of epidemiological data, experimental evidence on animals as well as the mechanisms of carcinogenesis. PMID- 26268880 TI - Comparison of Initial Psychological Treatment Selections by US and Japanese Early Career Psychiatrists for Patients with Major Depression: A Case Vignette Study. AB - OBJECTIVE: The authors compared early-career psychiatrists' selection of psychological treatments for patients with mild to moderate major depressive disorder (MDD) in the US and Japan. METHODS: A total of 120 early-career psychiatrists from two residency programs in the US and Japan participated in web based surveys. The psychiatrists selected first- and second-line psychological treatments in response to two case vignettes of patients with mild and moderate MDD. RESULTS: Eighty-one psychiatrists (68%) returned the surveys, of whom 39 (48%) were American and 42 (52%) Japanese. In response to the mild MDD case, more US psychiatrists selected high-intensity psychological treatments (P < 0.001), whereas more Japanese psychiatrists selected low-intensity psychological treatments (P < 0.001). In both countries, more psychiatrists selected psychological treatment than medication. In response to the moderate MDD case, one third of the US psychiatrists selected high-intensity psychological treatments (P < 0.001), whereas half of the Japanese psychiatrists selected low intensity psychological treatments (P = 0.010). CONCLUSIONS: Residency training, availability of psychological treatments, and cultural beliefs may shape differences in treatment selections, which in turn may impact the dissemination and implementation of psychological treatment in clinical practice across cultures. PMID- 26268879 TI - ABO blood group alleles and prostate cancer risk: Results from the breast and prostate cancer cohort consortium (BPC3). AB - BACKGROUND: ABO blood group has been associated with risk of cancers of the pancreas, stomach, ovary, kidney, and skin, but has not been evaluated in relation to risk of aggressive prostate cancer. METHODS: We used three single nucleotide polymorphisms (SNPs) (rs8176746, rs505922, and rs8176704) to determine ABO genotype in 2,774 aggressive prostate cancer cases and 4,443 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). Unconditional logistic regression was used to calculate age and study-adjusted odds ratios and 95% confidence intervals for the association between blood type, genotype, and risk of aggressive prostate cancer (Gleason score >=8 or locally advanced/metastatic disease (stage T3/T4/N1/M1). RESULTS: We found no association between ABO blood type and risk of aggressive prostate cancer (Type A: OR = 0.97, 95%CI = 0.87 1.08; Type B: OR = 0.92, 95%CI =n0.77-1.09; Type AB: OR = 1.25, 95%CI = 0.98 1.59, compared to Type O, respectively). Similarly, there was no association between "dose" of A or B alleles and aggressive prostate cancer risk. CONCLUSIONS: ABO blood type was not associated with risk of aggressive prostate cancer. PMID- 26268881 TI - Impact of 2.45 GHz microwave radiation on the testicular inflammatory pathway biomarkers in young rats: The role of gallic acid. AB - The aim of this study was to investigate electromagnetic radiation (EMR) transmitted by wireless devices (2.45 GHz), which may cause physiopathological or ultrastructural changes, in the testes of rats. We addressed if the supplemental gallic acid (GA) may reduce these adverse effects. Six-week-old male Sprague Dawley rats were used in this study. Forty eight rats were equally divided into four groups, which were named: Sham, EMR only (EMR, 3 h day-1 for 30 days), EMR + GA (30 mg/kg/daily), and GA (30 mg/kg/daily) groups. Malondialdehyde (MDA) and total oxidant status (TOS) levels increased (p = 0.001 for both) in EMR only group. TOS and oxidative stress index (OSI) levels decreased in GA treated group significantly (p = 0.001 and p = 0.045, respectively). Total antioxidant status (TAS) activities decreased in EMR only group and increased in GA treatment group (p = 0.001 and p = 0.029, respectively). Testosterone and vascular endothelial growth factor (VEGF) levels decreased in EMR only group, but this was not statistically significant. Testosterone and VEGF levels increased in EMR+GA group, compared with EMR only group (p = 0.002), and also increased in GA group compared with the control and EMR only group (p = 0.044 and p = 0.032, respectively). Prostaglandin E2 (PGE2 ) and calcitonin gene releated peptide (CGRP) staining increased in tubules of the testes in EMR only group (p < 0.001 for both) and decreased in tubules of the testes in EMR+GA group (p < 0.001 for all parameters). In EMR only group, most of the tubules contained less spermatozoa, and the spermatozoon counts decreased in tubules of the testes. All these findings and the regenerative reaction, characterized by mitotic activity, increased in seminiferous tubules cells of the testes in EMR+GA group (p < 0.001). Long term EMR exposure resulted in testicular physiopathology via oxidative damage and inflammation. GA may have ameliorative effects on the prepubertal rat testes physiopathology. (c) 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1771-1784, 2016. PMID- 26268883 TI - Laparoscopic splenectomy for hereditary spherocytosis-preliminary report. AB - Splenectomy is considered standard surgical therapy in hereditary spherocytosis. The procedure is indicated in patients with severe anemia, recurrent hemolytic, and aplastic crises. The aim of the study was to assess treatment outcomes in patients with hereditary spherocytosis who underwent total or partial laparoscopic splenectomy. Fifteen patients aged 4-17 yr underwent laparoscopic splenectomy from 2009 to 2012. Partial and total splenectomies were performed (five and 10 children, respectively). Hematologic parameters, liver function tests, and splenic volume before and after the surgery were analyzed retrospectively. Total follow-up was 1-30 months. Hospitalization and operating time were similar in both groups. In partial splenectomy group, branches of splenic arteries gave better blood supply than short gastric vessels. In both groups, hematologic parameters were improved. Postoperative markedly elevated platelet count was maintained up to 6 months, and after that, platelet count gradually decreased to normal values. Bilirubin level was decreased in early postoperative period; however, it increased later to achieve levels lower than in preoperative period. No severe general infections were observed in both groups. Laboratory parameters (hemoglobin and bilirubin concentrations and RBC) after the surgery improved in all patients, and the effect was maintained during 12 months of follow-up. Platelet count increased significantly after the surgery and was maintained at high levels during the next 6 months. However, it returned to preoperative levels within a year after the surgery. Our study showed that partial splenectomy was not inferior to total splenectomy. However, full assessment requires longer follow-up and larger group of patients. PMID- 26268882 TI - Racial/Ethnic and Sex Differences in Emergency Medical Services Transport Among Hospitalized US Stroke Patients: Analysis of the National Get With The Guidelines Stroke Registry. AB - BACKGROUND: Differences in activation of emergency medical services (EMS) may contribute to racial/ethnic and sex disparities in stroke outcomes. The purpose of this study was to determine whether EMS use varied by race/ethnicity and sex among a current, diverse national sample of hospitalized acute stroke patients. METHODS AND RESULTS: We analyzed data from 398,798 stroke patients admitted to 1613 Get With The Guidelines-Stroke participating hospitals between October 2011 and March 2014. Multivariable logistic regression was used to evaluate the associations between combinations of racial/ethnic and sex groups with EMS use, adjusting for potential confounders including demographics, medical history, and stroke symptoms. Patients were 50% female, 69% white, 19% black, 8% Hispanic, 3% Asian, and 1% other, and 86% had ischemic stroke. Overall, 59% of stroke patients were transported to the hospital by EMS. White women were most likely to use EMS (62%); Hispanic men were least likely to use EMS (52%). After adjustment for patient characteristics, Hispanic and Asian men and women had 20% to 29% lower adjusted odds of using EMS versus their white counterparts; black women were less likely than white women to use EMS (odds ratio 0.75, 95% CI 0.72 to 0.77). Patients with weakness or paresis, altered level of consciousness, and/or aphasia were significantly more likely to use EMS than patients without each symptom; the observed racial/ethnic and sex differences in EMS use remained significant after adjustment for stroke symptoms. CONCLUSIONS: EMS use differed by race/ethnicity and sex. These contemporary data document suboptimal use of EMS transport among US stroke patients, especially by racial/ethnic minorities and those with less recognized stroke symptoms. PMID- 26268885 TI - Recurrent Laryngeal Nerve Paralysis after Esophagectomy: Respiratory Complications and Role of Nerve Reconstruction. AB - Recurrent laryngeal nerve paralysis (RLNP) after esophagectomy is a common complication and associated with aspiration pneumonia. In this study, we assessed the risk of RLNP and the usefulness of immediate reconstruction of recurrent laryngeal nerve (RLN) to prevent respiratory complications after esophagectomy. Seven hundred and eighty-two consecutive patients underwent an esophagectomy with three-field lymph node dissection, simultaneous gastric conduit reconstruction, and cervical anastomosis. Vocal cord function was observed using a flexible laryngoscope. Reconstruction between RLN and ipsilateral vagus nerve was performed during esophagectomy. RLNP was observed in 229 (29.3%) of the patients after esophagectomy: 198 unilateral and 31 bilateral cases. Of the 198 unilateral RLNP, vocal cord paralysis was observed predominantly on the left side (82.7%). RLNP was significantly associated with postoperative respiratory complications (P < 0.001) requiring a tracheotomy (P < 0.001) and mechanical ventilation (P < 0.001) and was also associated with esophagogastric anastomotic leakage (P = 0.015); consequently, the postoperative hospital stay was longer for patients with RLNP (P < 0.001). A longer operation time (P < 0.001) and advanced age (P = 0.038) were identified as significant independent predictors of RLNP. Resection of the RLN together with metastatic nodes was performed in 29 cases. The patients underwent RLN reconstruction (n = 11) had a significantly shorter postoperative hospital stay than those without RLN reconstruction (n = 18) (P = 0.019). In conclusion, RLNP was related to a poorer postoperative course among patients undergoing an esophagectomy. New surgical technologies are recommended for prevention of RLNP. PMID- 26268884 TI - Integrative systems analysis of diet-induced obesity identified a critical transition in the transcriptomes of the murine liver and epididymal white adipose tissue. AB - BACKGROUND: It is well known that high-fat diet (HFD) can cause immune system related pathological alterations after a significant body weight gain. The mechanisms of the delayed pathological alterations during the development of diet induced obesity (DIO) are not fully understood. METHODS: To elucidate the mechanisms underlying DIO development, we analyzed time-course microarray data obtained from a previous study. First, differentially expressed genes (DEGs) were identified at each time point by comparing the hepatic transcriptome of mice fed HFD with that of mice fed normal diet. Next, we clustered the union of DEGs and identified annotations related to each cluster. Finally, we constructed an 'integrated obesity-associated gene regulatory network (GRN) in murine liver'. We analyzed the epididymal white adipose tissue (eWAT) transcriptome usig the same procedure. RESULTS: Based on time-course microarray data, we found that the genes associated with immune responses were upregulated with an oscillating expression pattern between weeks 2 and 8, relatively downregulated between weeks 12 and 16, and eventually upregulated after week 20 in the liver of the mice fed HFD. The genes associated with immune responses were also upregulated at late stage, in the eWAT of the mice fed HFD. These results suggested that a critical transition occurred in the immune system-related transcriptomes of the liver and eWAT around week 16 of the DIO development, and this may be associated with the delayed pathological alterations. The GRN analysis suggested that Maff may be a key transcription factor for the immune system-related critical transition thatoccurred at week 16. We found that transcription factors associated with immune responses were centrally located in the integrated obesity-associated GRN in the liver. CONCLUSIONS: In this study, systems analysis identified regulatory network modules underlying the delayed immune system-related pathological changes during the development of DIO and could suggest possible therapeutic targets. PMID- 26268887 TI - A novel method of fabricating carbon nanotubes-polydimethylsiloxane composite electrodes for electrocardiography. AB - Polymer-based flexible electrodes are receiving much attention in medical applications due to their good wearing comfort. The current fabrication methods of such electrodes are not widely applied. In this study, polydimethylsiloxane (PDMS) and conductive additives of carbon nanotubes (CNTs) were employed to fabricate composite electrodes for electrocardiography (ECG). A three-step dispersion process consisting of ultrasonication, stirring, and in situ polymerization was developed to yield homogenous CNTs-PDMS mixtures. The CNTs PDMS mixtures were used to fabricate CNTs-PDMS composite electrodes by replica technology. The influence of ultrasonication time and CNT concentration on polymer electrode performance was evaluated by impedance and ECG measurements. The signal amplitude of the electrodes prepared using an ultrasonication time of 12 h and CNT content of 5 wt% was comparable to that of commercial Ag/AgCl electrodes. The polymer electrodes were easily fabricated by conventional manufacturing techniques, indicating a potential advantage of reduced cost for mass production. PMID- 26268886 TI - The selective post-translational processing of transcription factor Nrf1 yields distinct isoforms that dictate its ability to differentially regulate gene expression. AB - Upon translation, the N-terminal homology box 1 (NHB1) signal anchor sequence of Nrf1 integrates it within the endoplasmic reticulum (ER) whilst its transactivation domains [TADs, including acidic domain 1 (AD1), the flanking Asn/Ser/Thr-rich (NST) domain and AD2] are transiently translocated into the ER lumen, whereupon the NST domain is glycosylated to yield an inactive 120-kDa glycoprotein. Subsequently, these TADs are retrotranslocated into extra-luminal subcellular compartments, where Nrf1 is deglycosylated to yield an active 95-kDa isoform. Herein, we report that AD1 and AD2 are required for the stability of the 120-kDa Nrf1 glycoprotein, but not that of the non-glycosylated/de-glycosylated 95-kDa isoform. Degrons within AD1 do not promote proteolytic degradation of the 120-kDa Nrf1 glycoprotein. However, repositioning of AD2-adjoining degrons (i.e. DSGLS-containing SDS1 and PEST2 sequences) into the cyto/nucleoplasm enables selective topovectorial processing of Nrf1 by the proteasome and/or calpains to generate a cleaved active 85-kDa Nrf1 or a dominant-negative 36-kDa Nrf1gamma. Production of Nrf1gamma is abolished by removal of SDS1 or PEST2 degrons, whereas production of the cleaved 85-kDa Nrf1 is blocked by deletion of the ER luminal anchoring NHB2 sequence (aa 81-106). Importantly, Nrf1 activity is positively and/or negatively regulated by distinct doses of proteasome and calpain inhibitors. PMID- 26268888 TI - French multicentre clinical evaluation of helical TomoTherapy for anal cancer in a cohort of 64 consecutive patients. AB - PURPOSE/OBJECTIVES: To assess feasibility and toxicity of Helical TomoTherapy for treating anal cancer patients. METHODS: From 2007 to 2011, 64 patients were consecutively treated with TomoTherapy in three centres for locally advanced squamous-cell anal carcinoma (T2 > 4 cm or N positive). Prescribed doses were 45 Gy to the pelvis including inguinal nodes and 59.4 Gy to the primary site and involved nodes with fractions of 1.8 Gy, five days a week. A positional Megavoltage Computed Tomography was performed before each treatment session. All acute and late toxicities were graded according to Common Terminology Criteria for Adverse Events version 3.0. Survival analysis was performed using the Kaplan Meier method. RESULTS: Median follow-up was 22.9 months. Fifty-four women and 10 men were treated (median age: 62 years). Nineteen patients (29.7%) had T2, 16 patients (25.0%) T3, and 27 patients (42.2%) T4 tumours. Thirty-nine patients (60.9%) had nodal involvement. Median tumour size was 45 mm (range, 10-110 mm). Seven patients had a colostomy before treatment initiation. Fifty-seven patients received concomitant chemotherapy (5-FU/cisplatin or 5-FU/mitomycin-based therapy). Forty-seven patients (73.4 %) experienced a complete response, 13 a partial response or local recurrence, and 11 had salvage surgery; among these, six became complete responders, three experienced metastatic failure, and two local failure. At least four patients experienced metastatic recurrence (concomitant to a local failure for one patient). The two-year overall survival was 85.6% (95 %CI [71.1%-93.0%]), and the one-year disease-free survival, and colostomy-free survival were 68.7% (95 %CI [54.4%-79.4]), and 75.5% (95 %CI [60.7%-85.3%]) respectively. Overall survival, disease-free survival and colostomy free-survival were significantly better for women than men (p = 0.002, p = 0.004, and p = 0.002 respectively). Acute grade >=3 toxicity included dermatologic (46.9% of patients), gastrointestinal (20.3%), and hematologic (17.2%) toxicity. Acute grade 4 hematologic toxicity occurred in one patient. No grade 5 event was observed. CONCLUSIONS: TomoTherapy for locally advanced anal cancer is feasible. In our three centres of expertise, this technique appeared to produce few acute gastrointestinal toxicities. However, high rates of dermatologic toxicity were observed. The therapeutic efficacy was within the range of expectations and similar to previous studies in accordance with the high rates of locally advanced tumours and nodal involvement. PMID- 26268889 TI - A histopathological study of melanocytic and pigmented skin lesions in patients with albinism. AB - BACKGROUND: Oculocutaneous albinism (OCA) is a group of genetic disorders characterized by diminished pigmentation of the skin, hair and eyes. Individuals with OCA are at increased risk to develop sun-induced skin malignancies. The incidence of malignant melanoma in OCA individuals is, however, very low. The aim of this study was to document pigmented and melanocytic skin lesions occurring in patients with OCA. METHODS: A prospective study was performed. Sixteen patients with OCA presenting at the Oncology and Dermatology Departments at Universitas Academic Hospital Annex in Bloemfontein, South Africa, were included. Selected clinically pigmented and/or melanocytic lesions were biopsied and studied by light microscopy. RESULTS: Twenty-four punch biopsies were taken. Ten dendritic freckles and 10 melanocytic nevi were confirmed histologically. The nevi, which occurred in eight patients, were found on sun-protected skin. All the freckles occurred on sun-exposed skin. Twelve patients had current or previous skin malignancies. No melanomas were present in the study population. Other skin lesions ranged from solar keratoses to squamous cell carcinomas. CONCLUSION: The majority of pigmented lesions were dendritic freckles that occurred on sun exposed skin. None of the patients had a current or previous diagnosis of malignant melanoma. PMID- 26268890 TI - The use of paracetamol (acetaminophen) among a community sample of people with chronic non-cancer pain prescribed opioids. AB - BACKGROUND: The regular use of simple analgesics in addition to opioids such as paracetamol (or acetaminophen) is recommended for persistent pain to enhance analgesia. Few studies have examined the frequency and doses of paracetamol among people with chronic non-cancer pain including use above the recommended maximum daily dose. AIMS: To assess (i) the prevalence of paracetamol use among people with chronic non-cancer pain prescribed opioids, (ii) assess the prevalence of paracetamol use above the recommended maximum daily dose and (iii) assess correlates of people who used paracetamol above the recommended maximum daily dose including: age, gender, income, education, pain severity and interference, use of paracetamol/opioid combination analgesics, total opioid dose, depression, anxiety, pain self-efficacy or comorbid substance use, among people prescribed opioids for chronic non-cancer pain. METHODS: This study draws on baseline data collected for the Pain and Opioids IN Treatment (POINT) study and utilises data from 962 interviews and medication diaries. The POINT study is national prospective cohort of people with chronic non-cancer pain prescribed opioids. Participants were recruited from randomly selected pharmacies across Australia. RESULTS: Sixty-three per cent of the participants had used paracetamol in the past week (95% CI = 59.7-65.8). Among the paracetamol users 22% (95% CI = 19.3 24.6) had used paracetamol/opioid combination analgesics and 4.8% (95% CI = 3.6 6.3) had used paracetamol above the recommended maximum daily dose (i.e. > 4000 mg/day). Following binomial logistic regression (chi(2) = 25.98, df = 10, p = 0.004), people who had taken above the recommended maximum daily dose were less likely to have low income (AOR = 0.52, 95% CI = 0.27-0.99), more likely to use paracetamol/opioid combination analgesics (AOR = 2.01, 95% CI = 1.02-3.98) and more likely to take a higher opioid dose (AOR = 1.00, 95% CI = 1.00-1.01). CONCLUSION: The majority of people with chronic non-cancer pain prescribed opioids report using paracetamol appropriately. High income, use of paracetamol/opioid combination analgesics and higher opioid dose were independently associated with paracetamol use above the recommended maximum daily dose. PMID- 26268891 TI - Identification of a novel de novo GATA3 mutation in a patient with HDR syndrome. AB - We describe the case of a 21-year-old male with hypocalcaemia, hyperphosphataemia, recurrent limb twitch, deafness, proteinuria, increased serum creatinine and urea nitrogen levels, and shrinkage of both kidneys. Brain computed tomography showed intracranial calcifications. The patient was diagnosed with hypoparathyroidism, sensorineural deafness and renal dysplasia (HDR) syndrome. DNA sequence analysis of the GATA3 gene showed a novel de novo mutation, c. 529dupC (p. Arg177profs*126), in exon 2, resulting in a frameshift mutation with a premature stop codon after a new 126 amino acid sequence. We provide further evidence that HDR syndrome is caused by haploinsufficiency of GATA3. PMID- 26268892 TI - Thin polymer-layer decorated, structure adjustable crystals of nanoparticles. AB - Flattened polymer chain decorated crystals of nanoparticles (NPs) are observed for polymer-NP mixtures confined between two parallel substrates. In order to minimize the entropy loss, polymer chains instead of NPs aggregate at the substrate surfaces when the number of NPs is high enough to have the conformation of chains significantly disturbed. Increasing NP concentration to be much higher than that of polymer chains leads to an ordered arrangement of NPs in the central region, which are sandwiched between two thin layers of polymer chains. A scaling model regarding polymer chains consisting of packed correlation blobs is provided to clarify the physics mechanism behind the formation of thin polymer layer and the crystallization of NPs. The order structure of the crystallized NPs is shown to be switchable through an adjustment of the bulk concentrations of polymer chains and NPs. PMID- 26268893 TI - Is repeating FOLFIRINOX in the original dosage and treatment schedule tolerable in Japanese patients with pancreatic cancer? PMID- 26268894 TI - Response to Y. Sasaki et al.: Is repeating FOLFIRINOX in the original dosage and treatment schedule tolerable in Japanese patients with pancreatic cancer? PMID- 26268896 TI - Formation of broadband antireflective and superhydrophilic subwavelength structures on fused silica using one-step self-masking reactive ion etching. AB - Fused silica subwavelength structures (SWSs) with an average period of ~100 nm were fabricated using an efficient approach based on one-step self-masking reactive ion etching. The subwavelength structures exhibited excellent broadband antireflection properties from the ultraviolet to near-infrared wavelength range. These properties are attributable to the graded refractive index for the transition from air to the fused silica substrate that is produced by the ideal nanocone subwavelength structures. The transmittance in the 400-700 nm range increased from approximately 93% for the polished fused silica to greater than 99% for the subwavelength structure layer on fused silica. Achieving broadband antireflection in the visible and near-infrared wavelength range by appropriate matching of the SWS heights on the front and back sides of the fused silica is a novel strategy. The measured antireflection properties are consistent with the results of theoretical analysis using a finite-difference time-domain (FDTD) method. This method is also applicable to diffraction grating fabrication. Moreover, the surface of the subwavelength structures exhibits significant superhydrophilic properties. PMID- 26268897 TI - Bundle-forming alpha-helical peptide-dendron hybrid. AB - Peptides and dendrons are enticing building blocks from which to construct hybrid macromolecules because each can be prepared as monodisperse and sequence defined materials. Folding and assembly properties designed into the amino acid sequence of a peptide-dendron hybrid manifest in the formation of a dendronized bundle of alpha-helices. PMID- 26268898 TI - Lys39-Lysophosphatidate Carbonyl Oxygen Interaction Locks LPA1 N-terminal Cap to the Orthosteric Site and partners Arg124 During Receptor Activation. AB - Lysophosphatidic acid (LPA) receptor 1 (LPA1) is a member of the G protein coupled receptors mediating the biological response to LPA species. Lack of detailed mechanism underlying LPA/LPA1 interaction has hampered the development of specific antagonists. Here, novel N-terminal Lys39 has been identified as a key residue during LPA-type agonist binding and LPA1 activation. Analysis of the molecular dynamics (MD) trajectories showed that LPA-type agonist but not VPC 32183 (antagonist) evolved structures with classical GPCR activation signatures such as reduced cytoplasmic transmembrane (TM) 3/TM6 dynamic network, ruptured ionic lock, and formation of a continuous and highly ordered internal water pathway was also observed. In activated state, LPA-type agonists interact with Arg124 (R3.28), Gln125 (Q3.29), Lys294 (K7.36) and a novel N-terminal Lys39. Site directed mutagenesis showed complete loss of intracellular calcium mobilization in B103 cells expressing R3.28A and Lys39Ala when treated with LPA-type agonists. Structurally, LPA-type agonist via Carbonyl-oxygen/Lys39 interaction facilitated the formation of a hypothetical N-terminal cap tightly packed over LPA1 heptahelical bundle. This packing may represent a key mechanism to distinguish an apo-receptor from bound LPA1. PMID- 26268899 TI - SSADH deficiency in an adult: Venturing outside of the diagnostic box and inside of the registry. PMID- 26268900 TI - Natural history of succinic semialdehyde dehydrogenase deficiency through adulthood. AB - OBJECTIVE: The natural history of succinic semialdehyde dehydrogenase (SSADH) deficiency in adulthood is unknown; we elucidate the clinical manifestations of the disease later in life. METHODS: A 63-year-old man with long-standing intellectual disability was diagnosed with SSADH deficiency following hospitalization for progressive decline, escalating seizures, and prolonged periods of altered consciousness. We present a detailed review of his clinical course and reviewed our SSADH deficiency database adult cohort to derive natural history information. RESULTS: Of 95 patients in the database for whom age at diagnosis is recorded, there are 40 individuals currently aged 18 years or older. Only 3 patients were diagnosed after age 18 years. Of 25 adults for whom data are available after age 18, 60% have a history of epilepsy. Predominant seizure types are generalized tonic-clonic, absence, and myoclonic. EEGs showed background slowing or generalized epileptiform discharges in two-thirds of adults for whom EEG data were collected. History of psychiatric symptoms was prominent, with frequent anxiety, sleep disturbances, and obsessive-compulsive disorder. CONCLUSIONS: We identified patients older than 18 years with SSADH deficiency in our database following identification and review of a patient diagnosed in the seventh decade of life. The illness had a progressive course with escalating seizures in the index case, with fatality at age 63. Diagnosis in adulthood is rare. Epilepsy is more common in the adult than the pediatric SSADH deficiency cohort; neuropsychiatric morbidity remains prominent. PMID- 26268901 TI - Lower physical activity is associated with higher disease burden in pediatric multiple sclerosis. AB - OBJECTIVE: To evaluate the association between physical activity (PA) and multiple sclerosis (MS) disease activity, depression, and fatigue in a cohort of children with MS and monophasic acquired demyelinating syndrome (mono-ADS). METHODS: In this cross-sectional study of consecutive patients attending a specialized pediatric MS clinic, we administered the PedsQL Multidimensional Fatigue Scale, Center for Epidemiological Studies Depression Scale, and Godin Leisure-Time Exercise Questionnaire. Quantitative MRI analysis was performed to obtain whole brain and T2 lesion volume in a subset of participants (n = 60). RESULTS: A total of 110 patients (79 mono-ADS; 31 MS; 5-18 years; M:F 1:1.2) were included. Patients with MS reported less strenuous (33.21 +/- 31.88 metabolic equivalents [METs] vs 15.97 +/- 22.73 METs, p = 0.002) and total (44.48 +/- 39.35 METs vs 67.28 +/- 59.65 METs; p = 0.0291) PA than those with mono-ADS. Patients with MS who reported greater amounts of moderate PA METs had fewer sleep/rest fatigue symptoms (r = -0.4). Participation in strenuous PA was associated with smaller T2 lesion volumes (r = -0.66) and lower annualized relapse rate (r = 0.66). No associations were found between total brain volume and participation in PA. CONCLUSIONS: Children with MS are less physically active than children with mono-ADS. Reasons for this are unclear, but may be related to ongoing disease activity, perceived limitations, or symptoms such as depression or fatigue. Children with MS reporting higher levels of strenuous PA had lower T2 lesion volumes and lower relapse rates, suggesting a potential protective effect of strenuous PA in this population. Further longitudinal studies are needed to establish the relationship of PA to MS symptoms and disease activity in this population. PMID- 26268902 TI - Promoting physical activity to control multiple sclerosis from childhood. PMID- 26268903 TI - Derivation and validation of an accurate estimation of CD4 counts from the absolute lymphocyte count in virologically suppressed and immunologically reconstituted HIV infected adults. AB - BACKGROUND: A simple method to estimate CD4 counts in stable, HIV infected virologically-suppressed and immune-reconstituted adults could save the expense of unnecessary formal testing. METHODS: Using a baseline CD4 percent, CD4 counts were estimated from subsequent absolute lymphocyte counts (ALC) measured by an automated FBC machine (CD4 estimate calculated by the ALC multiplied by the baseline CD4 percent). The accuracy of this approach was established in a large, retrospective clinical laboratory dataset of virologically-suppressed HIV infected subjects. A case-control study explored important clinical factors for accurate estimates, and a heuristic algorithm was derived and validated in a random sample. RESULTS: Data from 3,630 subjects were available. CD4 counts were generally accurately estimated, with a mean 6.1 % underestimation. Overall 83.3 % of CD4 estimates were within 25 % of the actual values, with 12.1 % CD4 counts underestimated by more than 25 %, and 4.5 % overestimated. The CD4 count was increasingly underestimated with time from baseline, and the degree of underestimation correlated with baseline CD4 percent (p < 0.0001). From the case control study, baseline CD4 percent of >=20, no illness requiring hospitalization and more than a year since starting or switch of anti-retroviral therapy were identified as significant predictors of inaccurate estimates. Employing this simple algorithm, CD4 estimate accuracy improved to a mean 1.3 % underestimation, and the proportion of estimates within 25 % of the actual value increased to 93.4 %. CONCLUSIONS: In virologically-suppressed and immune-reconstituted HIV-infected adults, the CD4 count can be accurately estimated from the ALC using a baseline CD4 percent for at least 2 years after measurement. PMID- 26268904 TI - Two new cassane-type diterpenes from the seeds of Caesalpinia crista. AB - Two new cassane-type diterpenes, phangininoxys D and E (1 and 2), together with five known compounds were isolated from the seeds of Caesalpinia crista Linn. The structures of these compounds were elucidated by means of various spectroscopic analyses. All the isolated compounds were evaluated for cytotoxicity activities against HeLa, HT-29 and KB cell lines, and compound 7 showed moderate selective activities against KB cell line with an IC50 value of 17.1 MUM. PMID- 26268905 TI - Which factors influence MRI-pathology concordance of tumour size measurements in breast cancer? AB - OBJECTIVES: To assess MRI-pathology concordance and factors influencing tumour size measurement in breast cancer. MATERIALS AND METHODS: MRI tumour size (greatest diameter in anatomical planes (MRI-In-Plane) and greatest diameter along main tumour axis (MRI-MPR)) of 115 consecutive breast lesions (59 invasive lobular carcinoma, 46 invasive ductal carcinoma, and 10 ductal carcinoma in situ) was retrospectively compared to size measured at histopathology (pT size (Path TNM) and greatest tumour diameter as relevant for excision (Path-Diameter; reference standard)). Histopathological tumour types, preoperative palpability, surgical management, additional high-risk lesions, and BI-RADS lesion type (mass versus non-mass enhancements) were assessed as possible influencing factors. RESULTS: Systematic errors were most pronounced between MRI-MPR and Path-TNM (7.1 mm, limits of agreement (LoA) [-21.7; 35.9]), and were lowest between MRI-In Plane and Path-Diameter (0.2 mm, LoA [-19.7; 20.1]). Concordance rate of MRI-In Plane with Path-Diameter was 86% (97/113), overestimation 9% (10/113) and underestimation 5% (6/113); BI-RADS mass lesions were overestimated in 7% (6/81) versus 41% (13/32) for non-mass enhancements. On multivariate analysis only BI RADS lesion type significantly influenced MRI-pathology concordance (p < 0.001). 2/59 (3%) ILC did not enhance. CONCLUSION: Concordance rate varies according to the execution of MRI and histopathological measurements. Beyond this only non mass enhancement significantly predicted discordance. KEY POINTS: * Execution and scope of MRI and histopathological size measurements influence concordance rate. * Non-mass like enhancement predicts discordance. * Additional high-risk lesions in proximity of tumour do not cause measurement discordance. * Low percentage of ILC do not enhance at all. PMID- 26268906 TI - Multi-modal magnetic resonance imaging and histology of vascular function in xenografts using macromolecular contrast agent hyperbranched polyglycerol (HPG GdF). AB - Macromolecular gadolinium (Gd)-based contrast agents are in development as blood pool markers for MRI. HPG-GdF is a 583 kDa hyperbranched polyglycerol doubly tagged with Gd and Alexa 647 nm dye, making it both MR and histologically visible. In this study we examined the location of HPG-GdF in whole-tumor xenograft sections matched to in vivo DCE-MR images of both HPG-GdF and Gadovist. Despite its large size, we have shown that HPG-GdF extravasates from some tumor vessels and accumulates over time, but does not distribute beyond a few cell diameters from vessels. Fractional plasma volume (fPV) and apparent permeability surface area product (aPS) parameters were derived from the MR concentration-time curves of HPG-GdF. Non-viable necrotic tumor tissue was excluded from the analysis by applying a novel bolus arrival time (BAT) algorithm to all voxels. aPS derived from HPG-GdF was the only MR parameter to identify a difference in vascular function between HCT116 and HT29 colorectal tumors. This study is the first to relate low and high molecular weight contrast agents with matched whole tumor histological sections. These detailed comparisons identified tumor regions that appear distinct from each other using the HPG-GdF biomarkers related to perfusion and vessel leakiness, while Gadovist-imaged parameter measures in the same regions were unable to detect variation in vascular function. We have established HPG-GdF as a biocompatible multi-modal high molecular weight contrast agent with application for examining vascular function in both MR and histological modalities. PMID- 26268907 TI - Iodine deficiency in pregnant women in Europe. PMID- 26268908 TI - Iodine deficiency in pregnant women in the UK: the costs of inaction. PMID- 26268909 TI - CCR2 inhibition: a panacea for diabetic kidney disease? PMID- 26268911 TI - Costs and benefits of iodine supplementation for pregnant women in a mildly to moderately iodine-deficient population: a modelling analysis. AB - BACKGROUND: Results from previous studies show that the cognitive ability of offspring might be irreversibly damaged as a result of their mother's mild iodine deficiency during pregnancy. A reduced intelligence quotient (IQ) score has broad economic and societal cost implications because intelligence affects wellbeing, income, and education outcomes. Although pregnancy and lactation lead to increased iodine needs, no UK recommendations for iodine supplementation have been issued to pregnant women. We aimed to investigate the cost-effectiveness of iodine supplementation versus no supplementation for pregnant women in a mildly to moderately iodine-deficient population for which a population-based iodine supplementation programme--for example, universal salt iodisation--did not exist. METHODS: We systematically searched MEDLINE, Embase, EconLit, and NHS EED for economic studies that linked IQ and income published in all languages until Aug 21, 2014. We took clinical data relating to iodine deficiency in pregnant women and the effect on IQ in their children aged 8-9 years from primary research. A decision tree was developed to compare the treatment strategies of iodine supplementation in tablet form with no iodine supplementation for pregnant women in the UK. Analyses were done from a health service perspective (analysis 1; taking direct health service costs into account) and societal perspective (analysis 2; taking education costs and the value of an IQ point itself into account), and presented in terms of cost (in sterling, relevant to 2013) per IQ point gained in the offspring. We made data-supported assumptions to complete these analyses, but used a conservative approach that limited the benefits of iodine supplementation and overestimated its potential harms. FINDINGS: Our systematic search identified 1361 published articles, of which eight were assessed to calculate the monetary value of an IQ point. A discounted lifetime value of an additional IQ point based on earnings was estimated to be L3297 (study estimates range from L1319 to L11,967) for the offspring cohort. Iodine supplementation was cost saving from both a health service perspective (saving L199 per pregnant woman [sensitivity analysis range -L42 to L229]) and societal perspective (saving L4476 per pregnant woman [sensitivity analysis range L540 to L4495]), with a net gain of 1.22 IQ points in each analysis. Base case results were robust to sensitivity analyses. INTERPRETATION: Iodine supplementation for pregnant women in the UK is potentially cost saving. This finding also has implications for the 1.88 billion people in the 32 countries with iodine deficiency worldwide. Valuation of IQ points should consider non-earnings benefits--eg, health benefits associated with a higher IQ not germane to earnings. FUNDING: None. PMID- 26268912 TI - Mechanochromic Luminescence of Aggregation-Induced Emission Luminogens. AB - Mechanochromic (MC) luminogens have found promising applications in mechanosensors, security papers, and optical storage for their change in emission behaviors in response to mechanical stimuli. Examples on MC luminescent materials are rare before the discovery of MC luminescence in aggregation-induced emission (AIE) luminogens. The twisted conformations of AIE luminogens (AIEgens) with appropriate crystallization capability afford loosely packing patterns, which facilitates their phase transformation in the solid state. The amorphous films of AIEgens exhibit enhanced emission intensity upon pressurization due to the increased molecular interactions, whereas crystals of AIEgens exhibit MC luminescence due to their amorphization by mechanical stimuli. AIEgens enrich the type of MC luminogens but those showing high emission contrast and multicolor emission switching and those working in a turn-on emission mode are seldom reported. Disclosure of the design strategy of high performance MC luminogens and exploration of their high-tech applications may be the future research directions for MC luminogens. PMID- 26268910 TI - The effect of CCR2 inhibitor CCX140-B on residual albuminuria in patients with type 2 diabetes and nephropathy: a randomised trial. AB - BACKGROUND: Patients with type 2 diabetes and nephropathy have high cardiorenal morbidity and mortality despite optimum treatment including angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Residual risk is related to residual albuminuria. We assessed whether CCX140-B, a selective inhibitor of C-C chemokine receptor type 2 (CCR2), could further reduce albuminuria when given in addition to standard care, including ACE inhibitors or ARBs. METHODS: In this randomised, double-blind, placebo-controlled clinical trial, we recruited patients from 78 research centres in Belgium, Czech Republic, Germany, Hungary, Poland, and the UK. We enrolled patients with type 2 diabetes aged 18-75 years with proteinuria (first morning void urinary albumin to creatinine ratio [UACR] 100-3000 mg/g), estimated glomerular filtration rate of 25 mL/min per 1.73 m(2) or higher, and taking stable antidiabetic treatment and ACE inhibitors or ARBs, for at least 8 weeks before study entry. Patients were stratified based on baseline UACR and renal function (estimated glomerular filtration rate), and then randomly assigned (1:1:1) via an interactive web response system with a minimisation algorithm to oral placebo, 5 mg CCX140-B, or 10 mg CCX140-B once a day. The 12-week dosing period in the initial protocol was extended to 52 weeks by protocol amendment. The primary efficacy measure was change from baseline in UACR during 52 weeks in the modified intention-to-treat population (all patients with uninterrupted dosing, excluding patients who stopped dosing at week 12 either permanently under the original protocol, or temporarily because of delay in approval of the protocol amendment). We did safety analyses on all randomly assigned patients who received at least one dose of study drug. According to a prespecified analysis plan, we analysed the primary endpoint with one-sided statistical testing with calculation of upper 95% confidence limits of the differences between active and control. This trial is registered with ClinicalTrials.gov, number NCT01447147. FINDINGS: The study ran from Dec 7, 2011 (first patient enrolled), until Aug 4, 2014. We enrolled 332 patients: 111 were assigned to receive placebo, 110 to 5 mg CCX140-B, and 111 to 10 mg CCX140-B. Of these, 192 were included in the modified intention-to-treat population. UACR changes from baseline during 52 weeks were -2% for placebo (95% CI -11% to 9%), -18% for 5 mg CCX140-B (-26% to -8%), and -11% for 10 mg CCX140-B (-20% to -1%). We recorded a -16% difference between 5 mg CCX140-B and placebo (one-sided upper 95% confidence limit -5%; p=0.01) and a -10% difference between 10 mg CCX140-B and placebo (upper 95% confidence limit 2%; p=0.08). Adverse events occurred in 81 (73%) of 111 patients in the placebo group versus 71 (65%) of 110 patients in the CCX140-B 5 mg group and 68 (61%) of 111 patients in the CCX140-B 10 mg group; there were no renal events during the study. INTERPRETATION: Our data suggest that CCR2 inhibition with CCX140-B has renoprotective effects on top of current standard of care in patients with type 2 diabetes and nephropathy. FUNDING: ChemoCentryx. PMID- 26268913 TI - Are High Proanthocyanidins Key to Cranberry Efficacy in the Prevention of Recurrent Urinary Tract Infection? AB - Most research on American cranberry in the prevention of urinary tract infection (UTI) has used juices. The spectrum of components in juice is limited. This study tested whether whole cranberry fruit powder (proanthocyanidin content 0.56%) could prevent recurrent UTI in 182 women with two or more UTI episodes in the last year. Participants were randomized to a cranberry (n = 89) or a placebo group (n = 93) and received daily 500 mg of cranberry for 6 months. The number of UTI diagnoses was counted. The intent-to-treat analyses showed that in the cranberry group, the UTIs were significantly fewer [10.8% vs. 25.8%, p = 0.04, with an age-standardized 12-month UTI history (p = 0.01)]. The Kaplan-Meier survival curves showed that the cranberry group experienced a longer time to first UTI than the placebo group (p = 0.04). Biochemical parameters were normal, and there was no significant difference in urinary phenolics between the groups at baseline or on day180. The results show that cranberry fruit powder (peel, seeds, pulp) may reduce the risk of symptomatic UTI in women with a history of recurrent UTIs. PMID- 26268914 TI - A role model for iconoclasts. PMID- 26268915 TI - Apple's ResearchKit: smart data collection for the smartphone era? PMID- 26268916 TI - 'Circumcision pain' unlikely to cause autism. PMID- 26268917 TI - Circumcision-autism link needs thorough evaluation: Response to Morris and Wiswell. PMID- 26268918 TI - Why did I become a clinician-trialist? PMID- 26268922 TI - Improving help-seeking among adolescents: A school-based intervention. PMID- 26268923 TI - Effect of transmeridian travel and jetlag on mood disorders: evidence and implications. AB - OBJECTIVES: Given the sensitivity of individuals with mood disorders to circadian disruption, transmeridian travel would likely be a high-risk endeavour leading to onset or relapses in mood. A systematic review was undertaken to identify the evidence of the impact of transmeridian travel on people with mood disorders. METHODS: Databases search included the following: CINAHL, MEDLINE, PsycINFO and manual searching using the keywords jetlag, transmeridian travel, circadian rhythm disruption, mood disorder, bipolar, major depression, seasonal affective disorder, depression, mania and hypomania. RESULTS: Only three studies were identified that related to transmeridian travel and jetlag in people with mood disorders. There is some suggestion that transmeridian travel does appear to precipitate mood episodes with an increased rate of episodes of depression with westward compared with an increased rate of manic/hypomanic episodes with eastward travel. Individuals with a previous history of mood disorder appear to be more vulnerable if adherence to medication is compromised. CONCLUSION: Given the limited evidence that transmeridian travel precipitates mood episodes, this poses difficulties in identifying suitable ways to mitigate the effects of transmeridian travel in mood disorders. However, in the absence of mood-specific guidelines, some guidance can be given based on our current understanding of the relevance of circadian disruption to both jetlag and mood disorders. Further research is required to identify more focused strategies to mitigate the impact of transmeridian travel for individuals with mood disorders. PMID- 26268924 TI - Phase 1 study of APTO-253 HCl, an inducer of KLF4, in patients with advanced or metastatic solid tumors. AB - INTRODUCTION: This phase I, multicenter, open-label, single-arm, dose-escalation study evaluated the safety, pharmacokinetics and antitumor activity of APTO-253, an inducer of the transcription factor KLF4, in adults with advanced solid tumors. METHODS: APTO-253 was administered IV on days 1 and 2, and 15 and 16 of each 28 day cycle; the dose were escalated from 20 to 387 mg/m(2) in 9 cohorts until DLT was observed. RESULTS: Thirty-two patients were treated on this trial (50 % colon cancer, 22 % other gastrointenstinal malignancies and 18 % non-small cell lung cancer). Fatigue was the only drug-related treatment-emergent adverse event to occur in >10 % of patients. Dose-limiting toxicities of hypersensitivity reaction and transient hypotension despite prophylaxis occurred at 387 mg/m(2) which led to identification of 298 mg/m(2) as the MTD. Only 1 patient had any drug-related treatment-emergent grade 3 adverse event at or below 229 mg/m(2). A total of 21 patients underwent at least one restaging after 2 cycles; 11 patients discontinued prior to the end of cycle 2 due to adverse events (9) or disease progression (2). The best overall response was stable disease (SD) in 5 of these 21 (23.8 %) with durations ranging from 3.6 to 8.4 months. CONCLUSION: APTO-253 was well tolerated at the Phase 2 recommended dose and produced evidence of antitumor activity in the form of stable disease in patients with advanced solid tumors. Based on the drug levels achieved and the lower frequency of treatment emergent adverse events encountered, 229 mg/m(2) was selected as the recommended Phase 2 dose. Overall APTO-253 was found to be well tolerated and to have favorable pharmacokinetics, and treatment was associated with stable disease in 5 of 21 (24 %) of patients with far advanced solid tumors. PMID- 26268925 TI - Subcellular localization of anthracyclines in cultured rat cardiomyoblasts as possible predictors of cardiotoxicity. AB - In this study, we compared the cellular uptake, intracellular localization and cytotoxicity of two groups of anthracycline derivatives in cultured H9c2(2-1) rat cardiomyoblasts. The first group consisted of doxorubicin (DOX) and two of its derivatives containing a formamidino group (-N = CH-N<) at the C-3' position with a morpholine (DOXM) or a hexamethyleneimine (DOXH) ring. The second group consisted of daunorubicin (DRB) and its derivatives containing a morpholine (DRBM) or a hexamethyleneimine (DRBH) ring. DOXH and DRBH were taken up by cardiomyoblasts more efficiently than estimated for other tested anthracyclines. The cellular uptakes of DOXM and DRBM were reduced compared to those of the parent compounds. Applied structural modifications of DOX and DRB influenced the subcellular localization of the tested derivatives. DOX and DOXH were localized primarily in nuclei, whereas the other anthracyclines were found in the nuclei and cytoplasm. The percentages of the compounds that accumulated in the nuclei were 80.2 and 54.2 % for DOX and DOXH, respectively. The lowest nuclear accumulation values were observed for DRBM (19.9 %), DRBH (21.9 %) and DOXM (23.7 %). The ability of anthracyclines to accumulate in the nuclei correlated with their DNA binding constants (r = 0.858, P = 0.029). A correlation was found between the accumulation of the tested anthracyclines in the nuclei of cardiomyoblasts and their cardiotoxicity in vivo, which was observed in our previous study. We suggest that cytotoxicity and the anthracycline accumulation level in the nuclei of cultured cardiomyoblasts could be used for early prediction of their cardiotoxicity. PMID- 26268927 TI - Heritable CRISPR/Cas9-mediated targeted integration in Xenopus tropicalis. AB - Xenopus tropicalis is an emerging vertebrate genetic model. A gene knock-in method has not yet been reported in this species. Here, we report that heritable targeted integration can be achieved in this diploid frog using a concurrent cleavage strategy mediated by the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (CRISPR/Cas9) system. The key point of the strategy is the addition of a Cas9/guide RNA cleavage site in the donor vector, allowing simultaneous cutting of the chromosomal target site and circular donor DNA in vivo. For the 3 distinct loci tested, all showed efficient targeted integration that was verified by both germ line transmission and Southern blot analyses. By designing the target sites in introns, we were able to get precise editing of the tyrosinase coding sequence and green fluorescent protein expression from endogenous n-tubulin promoter and enhancers. We were unable to detect off-target effects with the T7 endonuclease I assay. Precise editing of protein coding sequences in X. tropicalis expands the utility of this diploid frog, such as for establishing models to study human inherited diseases. PMID- 26268926 TI - Inhibition of Wnt/beta-catenin pathway promotes regenerative repair of cutaneous and cartilage injury. AB - Wound healing in mammals is a fibrotic process. The mechanisms driving fibrotic (as opposed to regenerative) repair are poorly understood. Herein we report that therapeutic Wnt inhibition with topical application of small-molecule Wnt inhibitors can reduce fibrosis and promote regenerative cutaneous wound repair. In the naturally stented model of ear punch injury, we found that Wnt/beta catenin pathway is activated most notably in the dermis of the wound bed early (d 2) after injury and subsides to baseline levels by d10. Topical application of either of 2 mechanistically distinct small-molecule Wnt pathway inhibitors (a tankyrase inhibitor, XAV-939, and the U.S. Food and Drug Administration-approved casein kinase activator, pyrvinium) in C57Bl/6J mice resulted in significantly increased rates of wound closure (72.3 +/- 14.7% with XAV-939; and 52.1 +/- 20.9% with pyrvinium) compared with contralateral controls (38.1 +/- 23.0 and 40.4.+/- 16.7%, respectively). Histologically, Wnt inhibition reduced fibrosis as measured by alpha-smooth muscle actin positive myofibroblasts and collagen type I alpha1 synthesis. Wnt inhibition also restored skin architecture including adnexal structures in ear wounds and dermal-epidermal junction with rete pegs in excisional wounds. Additionally, in ear punch injury Wnt inhibitor treatment enabled regeneration of auricular cartilage. Our study shows that pharmacologic Wnt inhibition holds therapeutic utility for regenerative repair of cutaneous wounds. PMID- 26268928 TI - Endothelin-1 as a master regulator of whole-body Na+ homeostasis. AB - The current study was designed to determine whether vascular endothelial-derived endothelin-1 (ET-1) is important for skin Na(+) buffering. In control mice (C57BL/6J), plasma Na(+) and osmolarity were significantly elevated in animals on high- vs. low-salt (HS and LS, respectively) intake. The increased plasma Na(+) and osmolarity were associated with increased ET-1 mRNA in vascular tissue. There was no detectable difference in skin Na(+):H2O in HS fed mice (0.119 +/- 0.005 mM vs. 0.127 +/- 0.007 mM; LS vs. HS); however, skin Na(+):H2O was significantly increased by blockade of the endothelin type A receptor with ABT-627 (0.116 +/- 0.006 mM vs. 0.137 +/- 0.007 mM; LS vs. HS; half-maximal inhibitory concentration, 0.055 nM). ET-1 peptide content in skin tissue was increased in floxed control animals on HS (85.9 +/- 0.9 pg/mg vs. 106.4 +/- 6.8 pg/mg; P < 0.05), but not in vascular endothelial cell endothelin-1 knockout (VEET KO) mice (76.4 +/- 5.7 pg/mg vs. 65.7 +/- 7.9 pg/mg; LS vs. HS). VEET KO mice also had a significantly elevated skin Na(+):H2O (0.113 +/- 0.007 mM vs. 0.137 +/- 0.005 mM; LS vs. HS; P < 0.05). Finally, ET-1 production was elevated in response to increasing extracellular osmolarity in cultured human endothelial cells. These data support the hypothesis that increased extrarenal vascular ET-1 production in response to HS intake is mediated by increased extracellular osmolarity and plays a critical role in regulating skin storage of Na(+). PMID- 26268929 TI - Paenibacillus kyungheensis sp. nov., isolated from flowers of magnolia. AB - A Gram-staining-positive, catalase-positive, oxidase-negative, facultatively anaerobic, rod-shaped bacterium designated strain DCY88T, was isolated from flowers of magnolia. Phylogenetic analysis based on 16S rRNA gene sequence comparison revealed that the strain formed a distinct lineage within the genus Paenibacillus that was closely related to Paenibacillus hordei RH-N24T (97.8 %). The other most closely related species were Paenibacillus illinoisensis NRRL NRS 1356T (94.3 %), Paenibacillus hunanensis DSM 22170T (94.2 %), Paenibacillus peoriae DSM 8320T (93.9 %), Paenibacillus kribbensis Am49T (93.8 %) and the type species of the genus, Paenibacillus polymyxa ATCC 842T (93.3 %). Cells of the strain were endospore-forming and motile by peritrichous flagella. Strain DCY88T formed pink-pigmented colonies on trypticase soy agar and R2A agar medium. Growth of strain DCY88T occurs at temperatures 5-37 degrees C, at pH 4-9 and 0.5-5.5 % NaCl (w/v). The menaquinone was MK-7.The cell wall peptidoglycan of strain DCY88T contained meso-diaminopimelic acid. The major fatty acids were anteiso-C15 : 0 (61.0 %) and C16 : 0 (11.0 %). The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and an unidentified polar lipid. The strain DCY88T contained spermidine as the major polyamine. The DNA G+C content was 51.6 mol%. The DNA-DNA hybridization relatedness between strain DCY88T and P. hordei RH-N24T was 48 +/- 2 %. The phenotypic, phylogenetic and chemotaxonomic results indicate that the strain DCY88T represents a novel species of the genus Paenibacillus, for which the name Paenibacillus kyungheensis sp. nov. is proposed. The type strain is DCY88T ( = JCM 19886T = KCTC 33429T). PMID- 26268931 TI - Percent Time With a Supratherapeutic INR in Atrial Fibrillation Patients Also Using an Antiplatelet Agent Is Associated With Long-Term Risk of Dementia. AB - BACKGROUND: Patients with atrial fibrillation (AF) are at higher risk of developing dementia. AF patients treated with warfarin with poor time in therapeutic ranges are significantly more likely to develop dementia. AF patients are also frequently treated with antiplatelet agents due to coexistent vascular disease. We hypothesize that AF patients with anticoagulation and antiplatelet therapies will be at higher risk of dementia, particularly with chronic exposure to over-anticoagulation. METHODS: Chronically anticoagulated patients receiving warfarin (target INR 2-3) for AF and managed by the Intermountain Healthcare Clinical Pharmacist Anticoagulation Service (CPAS) on concurrent antiplatelet agents with no history of dementia or stroke/TIA were included. The primary outcome was the presence of dementia defined by neurologist determined ICD-9 codes. Percent time with an INR>3.0 was determined and then compared by 3 strata <10% (n = 340), 10-24% (n = 417), >=25% (n = 235). Multivariable Cox hazard regression was utilized to determine dementia incidence by percent time. RESULTS: A total of 992 patients were studied. Patients with an INR>3 more than 25% of the time were 2.40 times more likely to develop dementia (P = 0.04). A comparison between < 10% group and 10-24.9% group with INR>3 indicated no difference in risk for the development of dementia (P = 0.74). The risk was significantly increased in patients using triple antithrombotic therapy, although the number of patients within this group was small. CONCLUSION: In AF patients receiving antiplatelet and anticoagulant therapies, the percent of time exposed to over-anticoagulation increased dementia risk. These data support the possibility of chronic cerebral injury from microbleeds as a mechanism underlying the association of AF and dementia. PMID- 26268930 TI - Effects of a pulmonary rehabilitation program on physical capacity, peripheral muscle function and inflammatory markers in asthmatic children and adolescents: study protocol for a randomized controlled trial. AB - BACKGROUND: Individuals with chronic lung disease are more susceptible to present reduction in exercise tolerance and muscles strength not only due to pulmonary limitations but also due systemic repercussions of the pulmonary disease. The aim of this study is to assess the physical capacity, peripheral muscle function, physical activity in daily life, and the inflammatory markers in children and adolescents with asthma after pulmonary rehabilitation program. METHOD: This is a study protocol of randomized controlled trial in asthmatic patients between 6 to 18 years old. The assessments will be conducted in three different days and will be performed at the beginning and at the end of the protocol. First visit: quality of life questionnaire, asthma control questionnaire, pre- and post bronchodilator spirometry (400 MUcg salbutamol), inflammatory assessment (blood collection), and cardiopulmonary exercise test on a cycle ergometer to determine aerobic capacity. Second visit: assessment of strength and endurance of the quadriceps femoris and biceps brachii muscles with concomitant electromyography to assess peripheral muscle strength. Third visit: incremental shuttle walk test (ISWT) and accelerometer to evaluate functional capacity and physical activity in daily life during 7 days. Then, the volunteers will be randomized to receive pulmonary rehabilitation program (intervention group) or chest physiotherapy + stretching exercises (control group). Both groups will have a supervised session, twice a week, each session will have 60 minutes duration, with minimum interval of 24 hours, for a period of 8 weeks. Intervention group: aerobic training (35 minutes) intensity between 60 to 80 % of the maximum workload of cardiopulmonary exercise testing or of ISWT; strength muscle training will be applied to the quadriceps femoris, biceps brachii and deltoid muscles (intensity: 40 to 70 % of maximal repetition, 3 x 8 repetition); finally the oral high-frequency oscillation device (Flutter(r)) will be used for 5 minutes. The control group: oral high-frequency oscillation device (Flutter(r)) for 10 minutes followed by the stretching of upper and lower limbs for 40 minutes. It is expected to observe the improvement in aerobic capacity, physical activity in daily life, muscle strength and quality of life of patients in the intervention group, and reduction in inflammatory markers. TRIAL REGISTRATION: CLINICAL TRIAL NUMBER: NCT02383069. Data of registration: 03/03/2015. PMID- 26268932 TI - Behavioral despair associated with a mouse model of Crohn's disease: Role of nitric oxide pathway. AB - Crohn's disease (CD) is associated with increased psychiatric co-morbidities. Nitric oxide (NO) is implicated in inflammation and tissue injury in CD, and it may also play a central role in pathogenesis of the accompanying behavioral despair. This study investigated the role of the NO pathway in behavioral despair associated with a mouse model of CD. Colitis was induced by intrarectal (i.r.) injection of 2,4,6-trinitrobenzenesulfonic acid (10mg TNBS in 50% ethanol). Forced swimming test (FST), pharmacological studies and tissues collection were performed 72 h following TNBS administration. To address a possible inflammatory origin for the behavioral despair following colitis induction, tumor necrosis factor-alpha (TNF-alpha) level was measured in both the hippocampal and colonic tissue samples. In parallel, hippocampal inducible nitric oxide synthase (iNOS) and nitrite level were evaluated. Pharmacological studies targeting the NO pathway were performed 30-60 min before behavioral test. Colitis was confirmed by increased colonic TNF-alpha level and microscopic score. Colitic mice demonstrated a significantly higher immobility time in the FST associated to a significant increase of hippocampal TNF-alpha, iNOS expression and nitrite content. Acute NOS inhibition using either Nomega-nitro-l-arginine methyl ester (a non-specific NOS inhibitor) or aminoguanidine hydrochloride (a specific iNOS inhibitor) decreased the immobility time in colitic groups. Moreover, acute treatment with both NOS inhibitors decreased the TNF-alpha level and nitrite content in the hippocampal samples. This study suggests that the NO pathway may be involved in the behavioral effects in the mouse TNBS model of CD. These findings endow new insights into the gut-brain communication during the development of colonic inflammation, which may ultimately lead to improved therapeutic strategies to combat behavior changes associated with gastrointestinal disorders. PMID- 26268933 TI - Consequences of paternally inherited effects on the genetic evaluation of maternal effects. AB - BACKGROUND: Mixed models are commonly used for the estimation of variance components and genetic evaluation of livestock populations. Some evaluation models include two types of additive genetic effects, direct and maternal. Estimates of variance components obtained with models that account for maternal effects have been the subject of a long-standing controversy about strong negative estimates of the covariance between direct and maternal effects. Genomic imprinting is known to be in some cases statistically confounded with maternal effects. In this study, we analysed the consequences of ignoring paternally inherited effects on the partitioning of genetic variance. RESULTS: We showed that the existence of paternal parent-of-origin effects can bias the estimation of variance components when maternal effects are included in the evaluation model. Specifically, we demonstrated that adding a constraint on the genetic parameters of a maternal model resulted in correlations between relatives that were the same as those obtained with a model that fits only paternally inherited effects for most pairs of individuals, as in livestock pedigrees. The main consequence is an upward bias in the estimates of the direct and maternal additive genetic variances and a downward bias in the direct-maternal genetic covariance. This was confirmed by a simulation study that investigated five scenarios, with the trait affected by (1) only additive genetic effects, (2) only paternally inherited effects, (3) additive genetic and paternally inherited effects, (4) direct and maternal additive genetic effects and (5) direct and maternal additive genetic plus paternally inherited effects. For each scenario, the existence of a paternally inherited effect not accounted for by the estimation model resulted in a partitioning of the genetic variance according to the predicted pattern. In addition, a model comparison test confirmed that direct and maternal additive models and paternally inherited models provided an equivalent fit. CONCLUSIONS: Ignoring paternally inherited effects in the maternal models for genetic evaluation can lead to a specific pattern of bias in variance component estimates, which may account for the unexpectedly strong negative direct-maternal genetic correlations that are typically reported in the literature. PMID- 26268934 TI - Long-term Surgical Outcomes of Epiretinal Membrane in Patients with Retinitis Pigmentosa. AB - Macular complications such as an epiretinal membrane (ERM), a cystoid macular edema and a macular hole lead to unexpected central vision impairment especially for patients with retinitis pigmentosa (RP). To evaluate the long-term surgical outcomes of pars plana vitrectomy (PPV) for ERM in patients with RP, we retrospectively reviewed the charts of a consecutive series of 10 RP patients who underwent PPV for ERM at Kyushu University Hospital. Visual acuity (VA) testing, a fundus examination, and an optical coherence tomography (OCT) analysis were conducted. The standard PPV using three sclerotomies was performed for ERM. PPV was performed in 12 eyes of 10 patients. One eye was excluded from the outcome assessment due to short period observation (18 months). There was no significantly deleterious change from the baseline to final VA between the operation eyes and the fellow eyes (P = 0.19). Moreover, morphological improvement was obtained in 9 of 11 eyes based on OCT. Our present data suggest that PPV may be tolerable in the management for ERM in RP patients over the long term. Furthermore, the appearance of the ellipsoid zone was an important factor in the prediction of visual outcome and determination of surgical indication. PMID- 26268935 TI - Efficacy and safety of weekly leflunomide for the treatment of early rheumatoid arthritis: a randomized, multi-center study. AB - AIM: The aim of this study was to determine the efficacy and safety of a weekly dose of leflunomide (50 mg/week) in early rheumatoid arthritis patients with mild or moderate disease activity. METHODS: The patients of early rheumatoid arthritis (ERA) with mild or moderate disease activity were randomly selected for inclusion in this study and were assigned to either the treatment group (leflunomide 50 mg/week, LEF50) or the control group (leflunomide 10 mg/day, LEF10). All patients were treated for 24 weeks. Clinical efficacy was assessed using the disease activity score in 28 joints (DAS28) - erythrocyte sedimentation rate (ESR) and European League Against Rheumatism (EULAR) response. A Chi-squared test, Fisher's exact-test and paired t-tests were used to analyze the data. RESULTS: A total of 244 patients who met the inclusion criteria and received at least one medicine dose were analyzed. At the baseline, the DAS28 (ESR) of the ERA patients were 4.41 +/- 0.69 in LEF 50 group and 4.52 +/- 0.64 in LEF 10 group, respectively. At week 24, the DAS28 (ESR) in two groups ( 2.94 +/- 1.10 and 3.02 +/- 1.14 ) were significant decreased compare with the baseline, respectively (P<0.01). There was no significant difference in DAS28 (ESR) between the LEF50 and LEF10 groups at week 24. (P > 0.05). At weeks 8, 12 and 24, the EULAR response (good responses + moderate responses) were 47.6%, 58.7% and 59.5%, in the LEF50 group and 43.2%, 49.1% and 53.4% in the LEF10 group, respectively. There was no significant different of EULAR response rates in the two groups at week 8, 12, and 24, respectively (P>0.05). There was no serious adverse events during the study. CONCLUSION: A weekly dose of 50 mg leflunomide showed similar benefits to a daily dose of 10 mg leflunomide for the treatment of mild-to-moderate early rheumatoid arthritis. PMID- 26268936 TI - In Response to 'Intravenous Lipid Emulsion Given to Volunteers Does Not Affect Symptoms of Lidocaine Brain Toxicity'. PMID- 26268937 TI - Mechanofluorochromism of 1-Alkanoylaminopyrenes. AB - To create a new series of mechanofluorochromic materials and to elucidate the mechanism of the phenomenon of mechanofluorochromism, 1-alkanoylaminopyrenes including 1-acetylaminopyrene (AAPy), 1-octanoylaminopyrene (OAPy), and 1 stearoylaminopyren (SAPy) were prepared. It was found that these materials exhibited mechanofluorochromism with emission colors in the crystalline samples changing reversibly from bluish purple to yellowish green, which could be induced by mechanical grinding. X-ray crystal structure analysis, electronic absorption, and fluorescence spectroscopies, as well as fluorescence lifetime analysis and powder X-ray diffraction analysis of AAPy suggested that the present mechanofluorochromism was caused by developing crystal defects through grinding. Intermolecular hydrogen bonds were suggested to play an important role in the occurrence of mechanofluorochromism, suppressing the face-to-face overlapping of pyrene moieties to form excimers in the pristine crystal. PMID- 26268938 TI - PARP inhibitors in the management of breast cancer: current data and future prospects. AB - Poly(ADP-ribose) polymerases (PARP) are enzymes involved in DNA-damage repair. Inhibition of PARPs is a promising strategy for targeting cancers with defective DNA-damage repair, including BRCA1 and BRCA2 mutation-associated breast and ovarian cancers. Several PARP inhibitors are currently in trials in the adjuvant, neoadjuvant, and metastatic settings for the treatment of ovarian, BRCA-mutated breast, and other cancers. We herein review the development of PARP inhibitors and the basis for the excitement surrounding these agents, their use as single agents and in combinations, as well as their toxicities, mechanisms of acquired resistance, and companion diagnostics. PMID- 26268940 TI - Comparison of acute kidney injury classifications in patients undergoing transcatheter aortic valve implantation: Predictors and long-term outcomes. AB - BACKGROUND: Acute kidney injury (AKI) was demonstrated to adversely affect outcome in patients undergoing transcatheter aortic valve implantation (TAVI). We compared predictors for AKI and associated outcomes according to various definitions among patients undergoing TAVI in a tertiary medical center. METHODS: Two-hundred and seventeen TAVI patients were evaluated for the occurrence of AKI according to Kidney Disease Improving Global Outcomes (KDIGO)/Valve Academic Research Consortium (VARC-2) and Risk Injury Failure Loss End-Stage (RIFLE) definitions. Multivariate analysis was conducted to assess predictors of AKI. Cox hazard ratio was used to evaluate long-term mortality in this patient population. RESULTS: AKI occurred in 23 and 21% of patients (n = 49, n = 46) according to KDIGO/VARC-2 and RIFLE definitions, respectively, with an approximate 10% of disagreement between both systems. Predictors of AKI according to KDIGO/VARC-2 were chronic obstructive pulmonary disease (COPD; OR = 2.66, P = 0.01), PVD (OR = 3.45, P = 0.02) and a lower baseline eGFR (OR = 1.03 per 1 mL/min/1.73 m(2) decrease, P = 0.02). While BMI (OR = 1.12, P = 0.01), prior ischemic heart disease (OR = 2.35, P = 0.04) and COPD (OR = 2.18, P = 0.04) were associated with AKI as defined by the RIFLE definition. AKI defined by either classification was independently associated with long-term mortality (HR = 1.63, for the KDIGO/VARC 2 definition and HR = 1.60 for RIFLE definition, P = 0.04 for both models), with borderline superiority of the KDIGO/VARC-2 classification. CONCLUSIONS: Different clinical characteristics predict the occurrence of AKI after TAVI when RIFLE and KDIGO/VARC-2 classifications are used. Both classification systems of AKI identify patients with increased risk for long-term mortality, with superiority of the KDIGO/VARC-2 definition, which should be used for AKI grading. PMID- 26268942 TI - The Cancer, Educate to Prevent Model-the Potential of School Environment for Primary Prevention of Cancer. AB - Cancer represents one of the main causes of death worldwide; consequently, preventive interventions are of utmost importance in public health education. The leading model of cancer prevention campaigns is based on general and undifferentiated actions mediated by health professionals, focusing on the technical and scientific information but rather ineffective in changing the symbolic, cognitive and practical relationship with the disease. New intervention models are thus required to address cancer literacy, being early interventions targeted to specific groups an elective counterpoint to contribute to positive and durable changes in cancer prevention. Our aim is to evaluate the feasibility and impact of cancer prevention programmes planned as focused interventions in restricted targets and mediated by non-healthcare professionals to increase cancer literacy and promote preventive behaviours. This pilot study evaluates schools' potential as a vehicle for cancer prevention education in a reality shaped by traditional health prevention campaigns. We developed a protocol of systematic surveying in order to review and, in the future, optimize and replicate this ecological model of intervention to other groups and contexts. The implementation of this model has been successful in which concerns to the effectiveness of the training programme for teachers. This led to the development of impactful cancer prevention education projects by trainees targeted to their students, allowing us to argue that it contributes to knowledge and practice in this complex as consensual priority area of intervention. PMID- 26268943 TI - Giving all pregnant women iodine supplements could save costs of cognitive impairment, study finds. PMID- 26268941 TI - Transcriptionally active LTR retrotransposons in Eucalyptus genus are differentially expressed and insertionally polymorphic. AB - BACKGROUND: In Eucalyptus genus, studies on genome composition and transposable elements (TEs) are particularly scarce. Nearly half of the recently released Eucalyptus grandis genome is composed by retrotransposons and this data provides an important opportunity to understand TE dynamics in Eucalyptus genome and transcriptome. RESULTS: We characterized nine families of transcriptionally active LTR retrotransposons from Copia and Gypsy superfamilies in Eucalyptus grandis genome and we depicted genomic distribution and copy number in two Eucalyptus species. We also evaluated genomic polymorphism and transcriptional profile in three organs of five Eucalyptus species. We observed contrasting genomic and transcriptional behavior in the same family among different species. RLC_egMax_1 was the most prevalent family and RLC_egAngela_1 was the family with the lowest copy number. Most families of both superfamilies have their insertions occurring <3 million years, except one Copia family, RLC_egBianca_1. Protein theoretical models suggest different properties between Copia and Gypsy domains. IRAP and REMAP markers suggested genomic polymorphisms among Eucalyptus species. Using EST analysis and qRT-PCRs, we observed transcriptional activity in several tissues and in all evaluated species. In some families, osmotic stress increases transcript values. CONCLUSION: Our strategy was successful in isolating transcriptionally active retrotransposons in Eucalyptus, and each family has a particular genomic and transcriptional pattern. Overall, our results show that retrotransposon activity have differentially affected genome and transcriptome among Eucalyptus species. PMID- 26268944 TI - Genotype and phenotype correlations in Iranian patients with hyperinsulinaemic hypoglycaemia. AB - BACKGROUND: Hyperinsulinaemic hypoglycaemia (HH) is a group of clinically and genetically heterogeneous disorders characterized by unregulated insulin secretion. Abnormalities in nine different genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A, UCP2 and HNF1A) have been reported in HH, the most common being ABCC8 and KCNJ11. We describe the genetic aetiology and phenotype of Iranian patients with HH. METHODS: Retrospective clinical, biochemical and genetic information was collected on 23 patients with biochemically confirmed HH. Mutation analysis was carried out for the ATP-sensitive potassium (K(ATP)) channel genes (ABCC8 and KCNJ11), GLUD1, GCK, HADH and HNF4A. RESULTS: 78% of the patients were identified to have a genetic cause for HH. 48% of patients had mutation in HADH, whilst ABCC8/KCNJ11 mutations were identified in 30% of patients. Among the diazoxide-responsive patients (18/23), mutations were identified in 72%. These include two novel homozygous ABCC8 mutations. Of the five patients with diazoxide-unresponsive HH, three had homozygous ABCC8 mutation, one had heterozygous ABCC8 mutation inherited from an unaffected father and one had homozygous KCNJ11 mutation. 52% of children in our cohort were born to consanguineous parents. Patients with ABCC8/KCNJ11 mutations were noted to be significantly heavier than those with HADH mutation (p = 0.002). Our results revealed neurodevelopmental deficits in 30% and epilepsy in 52% of all patients. CONCLUSIONS: To the best of our knowledge, this is the first study of its kind in Iran. We found disease-causing mutations in 78% of HH patients. The predominance of HADH mutation might be due to a high incidence of consanguineous marriage in this population. Further research involving a larger cohort of HH patients is required in Iranian population. PMID- 26268946 TI - Targeted grafting of thermoresponsive polymers from a penetrative honeycomb structure for cell sheet engineering. AB - Responsive membranes have been used to construct smart biomaterial interfaces. We report a novel approach to fabricate honeycomb films with a pattern of thermoresponsive polymer, namely poly(N-isopropylacrylamide). The approach was based on a combination of the breath figure method and reversible addition fragmentation chain transfer. The hybrid film had morphological and chemical patterns resulting in varied wettability and morphology at various stages, as well as high thermo-responsiveness. Enhanced cell adhesion was observed at an incubation temperature of 37 degrees C, which is above its lower critical solution temperature (LCST). Furthermore, cells could be harvested at temperatures below the LCST without trypsin treatment. The non-invasive characteristics give this membrane potential as a substrate for cell sheet engineering. PMID- 26268945 TI - Il-6 signaling between ductal carcinoma in situ cells and carcinoma-associated fibroblasts mediates tumor cell growth and migration. AB - BACKGROUND: Ductal carcinoma in situ (DCIS) is a non-obligate precursor lesion of invasive breast cancer in which approximately half the patients will progress to invasive cancer. Gaining a better understanding of DCIS progression may reduce overtreatment of patients. Expression of the pro-inflammatory cytokine interleukin-6 increases with pathological stage and grade, and is associated with poorer prognosis in breast cancer patients. Carcinoma associated fibroblasts (CAFs), which are present in the stroma of DCIS patients are known to secrete pro inflammatory cytokines and promote tumor progression. METHODS: We hypothesized that IL-6 paracrine signaling between DCIS cells and CAFs mediates DCIS proliferation and migration. To test this hypothesis, we utilized the mammary architecture and microenvironment engineering or MAME model to study the interactions between human breast CAFs and human DCIS cells in 3D over time. We specifically inhibited autocrine and paracrine IL-6 signaling to determine its contribution to early stage tumor progression. RESULTS: Here, DCIS cells formed multicellular structures that exhibited increased proliferation and migration when cultured with CAFs. Treatment with an IL-6 neutralizing antibody inhibited growth and migration of the multicellular structures. Moreover, selective knockdown of IL-6 in CAFs, but not in DCIS cells, abrogated the migratory phenotype. CONCLUSION: Our results suggest that paracrine IL-6 signaling between preinvasive DCIS cells and stromal CAFs represent an important factor in the initiation of DCIS progression to invasive breast carcinoma. PMID- 26268947 TI - Erectile function in men with end-stage liver disease improves after living donor liver transplantation. AB - BACKGROUND: Impaired liver function in men can result in erectile dysfunction or hypogonadism or both. We investigated whether living donor liver transplantation (LDLT) results in improvement in male sexual function. METHODS: A total of 58 patients with end-stage liver disease (ESLD) were included in this prospective, cross-sectional study. Erectile function was measured before and after LDLT using a five-item modified version of the International Index of Erectile Function scale (IIEF-5) and hypogonadism was evaluated before and after LDLT using the Androgen Deficiency in the Aging Male (ADAM) questionnaire. Differences in mean values from the questionnaires before and after the operation were than evaluated to determine whether there is an association between LDLT and improvement in sexual function. RESULTS: We found that mean IIEF-5 scores significantly increased after LDLT (from 11.7 +/- 7.7 before LDLT to 14.7 +/- 7.5 after LDLT, p < 0.01), indicating that the operation played a role in improving erectile function. In addition, the prevalence of hypogonadism among the patients with ESLD decreased markedly after liver transplantation (hypogonadism before LDLT, n = 41 versus hypogonadism after LDLT, n = 31, p = 0.03). Patients with hypogonadism reported a higher prevalence of erectile dysfunction after LDLT than patients without hypogonadism (p < 0.01). CONCLUSIONS: LDLT results in improvement in erectile function. In addition, improvement in erectile function is associated with self-reported absence of hypogonadism. PMID- 26268948 TI - Oxygen Insufflation in University of Wisconsin Solution Ameliorates Reperfusion Injury in Small Bowel after Cold Storage and Reperfusion. AB - BACKGROUND Results in small bowel transplantation are inferior compared to other solid organ transplantations, among other reasons, due to a specific vulnerability to ischemia/reperfusion injury. New strategies are needed to improve organ storage. Here we compare static cold storage in University of Wisconsin solution to storage supplemented with molecular oxygen gas insufflation. MATERIAL AND METHODS Rat small bowel was retrieved and either stored unoxygenated (UW) or oxygenated (UW+O2) for 18 h at 4 degrees C. Biochemical parameters, mucosal function, Toll-like receptor upregulation, and parameters of structural integrity were evaluated following isolated reperfusion in vitro for 30 min at 37 degrees C. RESULTS Oxygenation showed: ATP concentration was 82 times higher; lactate dehydrogenase release was continuously lower over 30 min; malondialdehyde, a final product of lipid peroxidation (UW+O2 vs. UW; 2.7+/-0.92 nmol/mL vs. 17.22+/-10.1 nmol/mL; P<0.05) and nitric oxide concentration (0.87+/-0.27 umol/L vs. 2.17+/-0.29 umol/L; P<0.001) were significantly lower; whereas mucosal functional integrity (galactose uptake) was better preserved (0.47+/-0.18 mg/dL vs. 0.35+/-0.05 mg/dL). Amelioration of tissue damage could be demonstrated by reduced apoptosis (3.3+/-1.2 AU vs. 28.4+/ 10 AU; P>0.05), and preserved subcellular integrity. Toll-like receptors were significantly less upregulated (TLR2 0.32+/-0.1 vs. 2.1+/-1.5-fold and TLR4 1.53+/-1.14 vs. 11.79+/-5.4-fold; P<0.05). CONCLUSIONS Oxygenated storage is superior to standard storage in University of Wisconsin solution in terms of energetics, tissue damage, and mucosal integrity. PMID- 26268949 TI - Progress and gaps in understanding mechanisms of ash tree resistance to emerald ash borer, a model for wood-boring insects that kill angiosperms. AB - We review the literature on host resistance of ash to emerald ash borer (EAB, Agrilus planipennis), an invasive species that causes widespread mortality of ash. Manchurian ash (Fraxinus mandshurica), which coevolved with EAB, is more resistant than evolutionarily naive North American and European congeners. Manchurian ash was less preferred for adult feeding and oviposition than susceptible hosts, more resistant to larval feeding, had higher constitutive concentrations of bark lignans, coumarins, proline, tyramine and defensive proteins, and was characterized by faster oxidation of phenolics. Consistent with EAB being a secondary colonizer of coevolved hosts, drought stress decreased the resistance of Manchurian ash, but had no effect on constitutive bark phenolics, suggesting that they do not contribute to increased susceptibility in response to drought stress. The induced resistance of North American species to EAB in response to the exogenous application of methyl jasmonate was associated with increased bark concentrations of verbascoside, lignin and/or trypsin inhibitors, which decreased larval survival and/or growth in bioassays. This finding suggests that these inherently susceptible species possess latent defenses that are not induced naturally by larval colonization, perhaps because they fail to recognize larval cues or respond quickly enough. Finally, we propose future research directions that would address some critical knowledge gaps. PMID- 26268951 TI - Implants with an Oxidized Surface Placed Predominately in Soft Bone Quality and Subjected to Immediate Occlusal Loading: Results from an 11-Year Clinical Follow Up. AB - PURPOSE: The purpose of this clinical follow-up was to document the 11-year outcome of implants with a moderately rough oxidized surface subjected to immediate occlusal loading. MATERIALS AND METHODS: Twenty-six of 38 patients enrolled in a 5-year prospective study were available for this follow-up analysis, with 33 restorations supported by 66 slightly tapered implants (Branemark System MkIV, Nobel Biocare, Gothenburg, Sweden). The majority of implants were placed in posterior regions (88%) and into soft bone (76%). Parameters included cumulative survival rate (CSR), radiographic marginal bone level, bleeding on probing (BOP), intrasulcular counts of perio-pathogenic markers (DNA probes), and total bacterial load (TBL). RESULTS: The CSR was 97.1% at 11.2 years mean follow-up. Mean marginal bone remodeling was 0.47 mm (SD 1.09, n = 65) from 1 year postplacement to 11-year follow-up. BOP was absent at most sites (63.6%). No statistically significant differences in TBL or perio pathogenic marker species were observed at implants and teeth. CONCLUSION: The results of the present follow-up show high long-term survival, stable marginal bone levels, and soft tissue outcomes of oxidized surface implants placed predominately in posterior regions and soft bone. The quantity and quality of intrasulcular microbiota were comparable at implants and teeth. PMID- 26268950 TI - Angiotensin II prevents calcification in vascular smooth muscle cells by enhancing magnesium influx. AB - BACKGROUND: Vascular calcification (VC) is highly prevalent in patients with chronic kidney disease (CKD). Low magnesium levels are associated with VC, and recent in vitro studies confirm a protective role of magnesium, which is mediated by its entry into the VSMCs through the Transient Receptor Potential Melastatin 7 (TRPM7) channel. The role of Angiotensin II (Ang II) on VC is still unclear. As Ang II is able to stimulate TRPM7 activity, we hypothesize that it might prevent VC. Thus, the aim of this study was to dissect the direct effect of Ang II on VC. MATERIALS AND METHODS: We worked with a model of high phosphate (HP)-induced calcification in human aortic smooth muscle cells, which resembles the CKD related VC. RESULTS: Addition of Ang II to cells growing in HP decreased calcification, which was associated with the upregulation of the osteogenic factors BMP2, Runx2/Cbfa1, Osterix and ALP. A reduction of magnesium entry into the HP-calcifying cells was found. The treatment with Ang II avoided this reduction, which was reversed by the cotreatment with the TRPM7-inhibitor 2-APB. The protective effect of Ang II was related to AT1R-induced ERK1/2 MAPKinase activation. HP-induced calcification was also associated with the upregulation of the canonical Wnt/beta-catenin pathway, while its downregulation was related to attenuation of calcification by Ang II. CONCLUSION: As hypothesized, Ang II prevented phosphate-induced calcification in VSMCs, which appears mediated by the increase of magnesium influx and by the activation of the ERK1/2 and the inhibition of the canonical Wnt/beta-catenin signalling pathways. PMID- 26268952 TI - Increase in pruritogenic kallikrein 5 in the skin of NC mice with chronic dermatitis. PMID- 26268953 TI - Synthesis, characterization and the release kinetics of antiproliferative agents from polyamidoamine conjugates. AB - Polyamidoamine conjugates containing curcumin and bisphosphonate were synthesized via a one-pot aqueous phase Michael addition reaction. In the design of the conjugate, bisphosphonate formed an integral part of the polymer carrier backbone. Curcumin was incorporated onto the polyamidoamine backbone via piperazine linker. The conjugates were characterized by Fourier transform spectroscopy, energy-dispersive X-ray analysis, atomic force spectroscopy and nuclear magnetic resonance spectroscopy and it confirmed the successful incorporation of the antiproliferative agents onto the carriers. The weight percentage incorporation of bisphosphonate to the carriers was found to be between 2.56% and 3.34%. The in vitro release studies of curcumin from the polyamidoamine conjugate were performed in dialysis bag at selected pH values. The release of curcumin was significantly slower at pH 7.4 when compared to pH 5.8. The release profiles indicate that the conjugates are more stable at pH 7.4 and are potential sustained drug-delivery systems for combination therapy. PMID- 26268954 TI - Role of sesamol-loaded floating beads in gastric cancers: a pharmacokinetic and biochemical evidence. AB - CONTEXT: Sesamol, a potential antioxidant with marked anticancer potential suffers from issues of extensive tissue distribution and local gastric irritation on oral administration. OBJECTIVE: To develop multiunit gastro-retentive floating beads (S-FBs) for localised and prolonged release of sesamol to treat gastric cancers. MATERIALS AND METHODS: S-FBs prepared using calcium carbonate, sodium alginate and hydroxypropylmethyl cellulose (HPMC) in different proportions, were characterised and evaluated in vivo in N-methyl-N-nitro-N-nitroguanidine-induced gastric cancer in rats. Single oral dose plasma pharmacokinetic study was also performed for free sesamol and S-FBs. RESULTS AND DISCUSSION: Restraining sesamol in floating beads, significantly lowered the release (diffusion controlled) rate, increased t50% (31 times) and reduced its in vivo clearance (>1.5 times). Preclinical evaluation showed S-FBs (10 mg/kg) to be significantly better than free sesamol and better/equivalent to methotrexate (2 mg/kg). CONCLUSION: Most of the natural phytochemical or antioxidants show pretreatment effectiveness. We, however, developed and established S-FBs for sustained curative effect. PMID- 26268955 TI - Fecal Incontinence: Etiology, Diagnosis, and Management. AB - INTRODUCTION: Fecal incontinence is a debilitating condition affecting primarily the elderly. Many patients suffer in silence resulting in both underdiagnosis and undertreatment often culminating in an overall poor quality of life. METHODS: We sought to review the etiology, diagnosis, and treatment of fecal incontinence based on current literature. Additionally, newer treatment methods such as Solesta will be evaluated. RESULTS: There are many diagnostic modalities available to assess the degree and severity of the patient's incontinence; however, a thorough history and physical exam is critical. Initial attempts at treatment focus on medical management primarily through stool texture modification with the aid of bulking agents. Failure of medical therapy is often followed by a graded increase in the complexity and invasiveness of the available treatment options. The selection of the most appropriate surgical option, such as overlapping sphincteroplasty and neuromodulation, is multifactorial involving both surgeon and patient-related factors. Neuromodulation has received increased attention in the last decade due to its documented therapeutic success, and newer office-based procedures, such as the Solesta injection, are showing promising results in properly selected patients. Finally, diversion remains an option for select patients who have failed all other therapies. CONCLUSION: The etiology of fecal incontinence is multifactorial, involving a complex interplay between stool consistency and anatomic integrity. The diagnosis and treatment of fecal incontinence continue to evolve and are showing promising results. PMID- 26268956 TI - Ideal Body Weight Calculation in the Bariatric Surgical Population. AB - BACKGROUND: In bariatric surgery, ideal body weight (IBW) is used to calculate excess body weight (EBW) and percent excess weight lost (%EWL). Bariatric literature typically uses the midpoint of the medium frame from older Metropolitan Life Insurance (MetLife) tables to estimate IBW. This is neither universal nor always clinically accurate. OBJECTIVE: The objective of this study was to determine the accuracy of standard IBW formulas compared to MetLife data. METHODS: Weight loss data from 200 bariatric surgical patients between 2009 and 2011 was used to assess the accuracy of IBW formulas. IBWs assigned from the midpoint of the medium frame and reassigned using different gender targets were compared to standard formulas and a new formula to assess the accuracy of all formulas to both targets. RESULTS: Using standard MetLife data, the mean IBW was 136 lb, the mean EBW was 153.6 lb, and the mean %EWL was 43.8 %. Using the new target baseline, the mean IBW was 137.1 lb, the mean EBW was 152.6 lb, and the mean %EWL was 44 %. Deitel and Greenstein's formula was accurate to 0.3 % of EBW using the standard method, while our new formula was accurate to 0.03 % of EBW. CONCLUSIONS: Deitel and Greenstein's formula is most accurate using standard target IBW. The most accurate is our formula using the new MetLife target IBW. PMID- 26268958 TI - Beyond physical access: a qualitative analysis into the barriers to policy implementation and service provision experienced by persons with disabilities living in a rural context. AB - INTRODUCTION: Persons with disabilities make up approximately 15% of the world's population, with vulnerable communities disproportionately affected by the incidence of disability. Research reflects that persons with disabilities are vulnerable to stigma and discrimination, social isolation, and have physical barriers to accessing support services, all of which serve to perpetuate a sense of uncertainty and vulnerability within their lives. Recently a number of policies and models of intervention have been introduced intended to protect the rights of those affected by disability, yet limited research has been conducted into the lived experiences of persons with disabilities, particularly in rural contexts. This implies that little is known about the impact of the rural context on the lived experience of disability and the ways in which context impacts on the implementation of policies and practices. METHODS: The current study employed a qualitative design underpinned by the principles of narrative inquiry and participant observation. Thirty adults with a variety of congenital and acquired disabilities (15 men and 15 women, ranging in age from 19 to 83 years) living in 12 rural communities in the Mpumalanga Province of South Africa were recruited through snowball sampling. Data collection comprised a combination of narrative inquiry and participant observation. Narratives were collected in SiSwati with the assistance of a SiSwati-speaking research mediator and were transcribed and translated into English. Data were analysed inductively according to the principles of thematic analysis. RESULTS: Findings confirmed that the experience of living with a disability in a rural area is associated with discrimination, social exclusion, and isolation and barriers to accessing services, underpinned by numerous context-specific experiences, including mortality rates, exposure to numerous and repeated forms of violence across the lifespan, and corruption and lack of transparency in the implementation of government policies and practices. These experiences are not currently reflected in the literature or in guidelines on the implementations of policies and service provision, and thus have the potential to offer novel insights into the barriers faced by persons with disabilities living in rural areas. CONCLUSIONS: The results of this study suggest that barriers to service provision extend beyond physical obstacles, and include a variety of sociocultural and sociopolitical barriers. By failing to take these into account, policies and current models of service provision are only able to provide limited support to persons with disabilities living in rural areas. The findings reveal narrative inquiry to be a powerful and culturally safe tool for exploring lived experience among vulnerable populations and hold significant implications for both practitioners and policy developers. Furthermore, it emerges that one-size-fits-all policies are unable to meet the needs of persons with disabilities living in rural areas. However, the implementation of site-specific needs analyses with the use of flexible and culturally appropriate tools has the potential to redress the discrepancies in policy implementation and can be used to strengthen institutional ties and referral pathways. PMID- 26268957 TI - Short- and Long-Term Outcomes After Laparoscopic Versus Open Total Gastrectomy for Elderly Gastric Cancer Patients: a Propensity Score-Matched Analysis. AB - BACKGROUND: To date, it has been unclear whether laparoscopic-assisted total gastrectomy (LTG) was a suitable treatment for elderly patients (aged 65 years and older) with gastric cancer. The aim of the present study was to clarify the value of LTG in the elderly using a propensity score matching method. METHODS: We prospectively collected data from 675 elderly gastric cancer patients who underwent total gastrectomies at our institution between January 2002 and February 2012. Propensity score matching was applied at a ratio of 1:1 to compare the LTG and open total gastrectomy (OTG) groups. The operation results, hospital courses, and survival rates were compared between the matched groups. RESULTS: The LTG group had a significantly shorter mean operating time (194 vs. 267 min, P < 0.001) and significantly less intraoperative blood loss (92 vs. 204 ml, P < 0.001). The total number of collected lymph nodes was similar in the two groups. Postoperatively, the length of hospital stay was shorter in the LTG group than in the OTG group (median 14.4 vs. 16.6 days; P = 0.001); however, no significant intergroup differences were found in morbidity or mortality. Furthermore, the 3 year overall survival (OS) rate was similar between the two groups (P = 0.517). CONCLUSIONS: LTG for elderly gastric cancer is feasible and safe with acceptable oncologic outcomes. Therefore, patient age alone should not be considered a contraindication in the decision between LTG and OTG treatment options. A high volume prospective study is needed to confirm this rationale. PMID- 26268960 TI - Assessment of Antioxidant and Antibacterial Potential of Medicinal Herbs and Botanical Preparations. PMID- 26268959 TI - Combined Ex Vivo 9.4T MRI and Quantitative Histopathological Study in Normal and Pathological Neocortical Resections in Focal Epilepsy. AB - High-resolution magnetic resonance imaging (MRI) may improve the preoperative diagnosis of focal cortical dysplasia (FCD) in epilepsy. Quantitative 9.4T MRI was carried out (T1, T2, T2* and magnetization transfer ratio) on 13 cortical resections, representing pathologically confirmed FCD (five cases) and normal cortex. Quantitative immunohistochemistry for myelination (myelin basic protein/SMI94), neuronal populations [microtubule-associated protein 2 (MAP2), neurofilament (SMI31, SMI32), synaptophysin, NeuN, calbindin], reactive glia (GFAP), microglia (CD68) and blood-brain barrier permeability (albumin) was carried out in 43 regions of interest (ROI) from normal and abnormal white matter and cortex. MRI was spatially aligned and quantitative analysis carried out on corresponding ROI. Line profile analysis (LPA) of intensity gradients through the cortex was carried out on MRI and immunostained sections. An inverse correlation was noted between myelin/SMI94 and T1, T2 (P < 0.005) and T2* (P < 0.05; Spearman's correlation) and a positive correlation between neuronal MAP2 and T1 (P < 0.005) and T2* (P < 0.05) over all ROI. Similar pathology-MRI correlations were observed for histologically unremarkable white matter ROI only. LPA showed altered gradient contours in regions of FCD, reflecting abnormal cortical lamination and myelo-architecture, including a preoperatively undetected FCD case. This study demonstrates the ability of quantitative 9.4T MRI to detect subtle differences in neuronal numbers and myelination in histologically normal appearing white matter and LPA in the evaluation of cortical dyslamination. These methods may be translatable to the in vivo detection of mild cortical malformations. PMID- 26268962 TI - TLC-Direct Bioautography and LC/MS as Complementary Methods in Identification of Antibacterial Agents in Plant Tinctures from the Asteraceae Family. AB - Matricaria recutita L. (chamomile) and Achillea millefolium L. (yarrow) are very common herbs growing in meadows, pathways, crop fields, and home gardens. Preparations from these plants, e.g., infusions or alcohol extracts, are widely used as remedies. Both chamomile and yarrow have anti-inflammatory, analgesic, antimicrobial, and antioxidant properties. Most microbiological assays used today give information only on activity of whole extracts and do not provide information on the composition and activity of individual components. This problem can be solved by using TLC with direct microbiological detection, i.e., TLC-direct bioautography (TLC-DB), followed by LC/MS of active fractions. The aim of our study was chemical and microbiological screening of plant components of chamomile and yarrow tinctures using derivatization reagents and TLC-DB against eight bacterial strains: Staphylococcus epidermidis, S. aureus, methicillin resistant S. aureus, Escherichia coli, Pseudomonas syringae pv. maculicola, Xanthomonas campestis pv. vesicatoria, Aliivibrio fischeri, and Bacillus subtilis. The identity of compounds exhibiting the widest range of activity (apigenin and alpha-linolenic acid) was confirmed by LC/MS. PMID- 26268961 TI - Direct Bioautography as a High-Throughput Screening Method for the Detection of Antibacterial Components from Plant Sources. AB - The applicability of direct bioautography, the combination of planar chromatography with antimicrobial assay, is demonstrated with special emphasis on its recent developments such as BioArena and the use of genetically modified luminescent bacteria. Its methodological advancement is put into a historical perspective. In comparison with other commonly used antimicrobial susceptibility tests, the main advantage of direct bioautography resides in its simplicity, rapidity, and ability to detect separated individual matrix components exhibiting antimicrobial activity in situ. It is confirmed with examples that high throughput direct bioautography is suitable as a biomonitoring-screening system for bioassay-guided isolation. PMID- 26268963 TI - Application of Electron Paramagnetic Resonance Spectroscopy for Investigating Antioxidant Activity of Selected Herbs. AB - Antioxidant properties of selected herbs were investigated using electron paramagnetic resonance (EPR) spectroscopy. This was possible by measuring changes in the intensity of the EPR spectrum that resulted from the interaction of the stable radical 1,1-diphenyl-2-picrylhydrazyl with antioxidants found in herbal samples. Moreover, the total phenolic content (TPC) was measured using UV-Vis spectroscopy. The values of trolox equivalent antioxidant capacity were in the range of 10.95 to 505.95 MUmol Trolox/1 g of dry weight of sample. TPC values were in the range of 3.38 to 63.13 mg of gallic acid/1 g of dry weight. The results showed that all of the investigated herbs exhibit antioxidant properties. A positive and significant correlation between antioxidant activity and total phenolic content was observed. The studied herbs could be a good source of natural antioxidants. PMID- 26268964 TI - Investigation of Antioxidant Activity of Pomegranate Juices by Means of Electron Paramagnetic Resonance and UV-Vis Spectroscopy. AB - Pomegranate fruit (Punica granatum L.) is a source of numerous phenolic compounds, and it contains flavonoids such as anthocyanins, anthocyanidins, cyanidins, catechins and other complexes of flavonoids, ellagitannins, and hydrolyzed tannins. Pomegranate juice shows antioxidant, antiproliferative, and anti-atherosclerotic properties. The antioxidant capacity (TEAC) of the pomegranate juices was measured using electron paramagnetic resonance (EPR) spectroscopy and 1,1-diphenyl-2-picrylhydrazyl (DPPH*) as a source of free radicals, and the total phenolic (TP) content was measured using UV-Vis spectroscopy. All the examined pomegranate juices exhibited relatively high antioxidant properties. The TEAC values determined by means of EPR spectroscopy using Trolox (TE) as a free radical scavenger were in the range of 463.12 to 1911.91 MUmol TE/100 mL juice. The TP content measured by the Folin-Ciocalteu method, using gallic acid (GA) as a free radical scavenger, widely varied in the investigated pomegranate juice samples and ranged from 1673.62 to 5263.87 mg GA/1 L juice. The strongest antioxidant properties were observed with the fresh pomegranate juices obtained from the fruits originating from Israel, Lebanon, and Azerbaijan. Correlation analysis of numerical data obtained by means of EPR spectroscopy (TEAC) and UV-Vis spectroscopy (TP) gave correlation coefficient (r)=0.90 and determination coefficient (r2)=0.81 (P<0.05). PMID- 26268965 TI - A Comparison of Antibacterial Activity of Selected Thyme (Thymus) Species by Means of the Dot Blot Test with Direct Bioautographic Detection. AB - Bioautography carried out with the aid of thin-layer chromatographic adsorbents can be used to assess antibacterial activity in samples of different origin. It can either be used as a simple and cost-effective detection method applied to a developed chromatogram, or to the dot blot test performed on a chromatographic plate, where total antibacterial activity of a sample is scrutinized. It was an aim of this study to compare antibacterial activity of 18 thyme (Thymus) specimens and species (originating from the same gardening plot and harvested in the same period of time) by means of a dot blot test with direct bioautography. A two-step extraction of herbal material was applied, and at step two the polar fraction of secondary metabolites was obtained under the earlier optimized extraction conditions [methanol-water (27+73, v/v), 130 degrees C]. This fraction was then tested for its antibacterial activity against Bacillus subtilis bacteria. It was established that all investigated extracts exhibited antibacterial activity, yet distinct differences were perceived in the size of the bacterial growth inhibition zones among the compared thyme species. Based on the results obtained, T. citriodorus "golden dwarf" (sample No. 5) and T. marschallianus (sample No. 6) were selected as promising targets for further investigations and possible inclusion in a herbal pharmacopeia, which is an essential scientific novelty of this study. PMID- 26268966 TI - Antioxidant Activity of Selected Thyme (Thymus L.) Species and Study of the Equivalence of Different Measuring Methodologies. AB - This study presents the results of comparative evaluation of the antioxidant activity of the phenolic fraction exhaustively extracted with aqueous methanol from 18 different thyme (Thymus L.) specimens and species. This evaluation is made with use of the same free radical source (DPPH* radical), three different free radical scavenging models (gallic acid, ascorbic acid, and Trolox), and three different measuring techniques (the dot blot test, UV-Vis spectrophotometry, and electron paramagnetic resonance spectroscopy, EPR). A comparison of the equivalence of these three different measuring techniques (performed with use of hierarchical clustering with Euclidean distance as a similarity measure and Ward's linkage) is particularly important in view of the fact that different laboratories use different antioxidant activity measuring techniques, which makes any interlaboratory comparison hardly possible. The results obtained confirm a semiquantitative equivalence among the three compared methodologies, and a proposal is made of a simple and cost-effective dot blot test that uses the DPPH* radical and provides differentiation of antioxidant activity of herbal matter comparable with the results of the UV-Vis spectrophotometry and EPR. PMID- 26268967 TI - Evaluation of Laboratory Procedures to Quantify the Neutral Detergent Fiber Content in Forage, Concentrate, and Ruminant Feces. AB - A comparison was made of measurements of neutral detergent fiber concentrations obtained with AOAC Method 2002.04 and modified methods using pressurized environments or direct use of industrial heat-stable alpha-amylase in samples of forage (n=37), concentrate (n=30), and ruminant feces (n=39). The following method modifications were tested: AOAC Method 2002.04 with replacement of the reflux apparatus with an autoclave or Ankom(220(r)) extractor and F57 filter bags, and AOAC Method 2002.04 with replacement of the standardization procedures for alpha-amylase by a single addition of industrial alpha-amylase [250 MUL of Termamyl 2X 240 Kilo Novo Units (KNU)-T/g] prior to heating the neutral detergent solution. For the feces and forage samples, the results obtained with the modified methods with an autoclave or modification of alpha-amylase use were similar to those obtained using AOAC Method 2002.04, but the use of the Ankom220 extractor resulted in overestimated values. For the concentrate samples, the modified methods using an autoclave or Ankom220 extractor resulted in positive systematic errors. However, the method using industrial alpha-amylase resulted in systematic error and slope bias despite that the obtained values were close to those obtained with AOAC Method 2002.04. PMID- 26268968 TI - Continuing Assessment of the 5-Day Sodium Carbonate-Ammonium Nitrate Extraction Assay as an Indicator Test for Silicon Fertilizers. AB - The 5-day sodium carbonate-ammonium nitrate extraction assay (5-day method) has been recognized by the American Association of Plant Food Control Officials as a validated test method to identify fertilizers or beneficial substances that provide plant-available silicon (Si). The test method used the molybdenum blue colorimetric assay to quantify percentage Si; however, laboratories may use inductively coupled plasma optical emission spectroscopy (ICP-OES) for elemental analysis. To examine the use of either colorimetric or ICP-OES methods for Si determination, the 5-day method was performed on the following Si-containing compounds; wollastonite, sand, biochar, and a basic oven furnace (BOF) slag. Grow out studies using Zinnia elegans were also performed using varying rates of the wollastonite, biochar, and BOF slag. Our results show using the 5-day method, wollastonite had the highest extracted amounts of silicic acid (H4SiO4) at 4% followed by biochar (2%), BOF slag (1%), and sand (0%). Extraction values calculated using either the molybdenum blue colorimetric assay or ICP-OES for detection of the H4SiO4 had a significant correlation, supporting the application of either detection method for this type of analysis. However, when extracted values were compared to amounts of Si taken up by the plants, the 5-day method overestimated both wollastonite and biochar. While this method is a valid indicator test for determining a soluble Si source, other plant species and methods should be perused to potentially provide more quantitative analyses for plant-available Si content of all materials. PMID- 26268969 TI - Determination of Yohimbine in Yohimbe Bark and Related Dietary Supplements Using UHPLC-UV/MS: Single-Laboratory Validation. AB - A single-laboratory validation was performed on a practical ultra-HPLC (UHPLC) diode array detector (DAD)/tandem MS method for determination of yohimbine in yohimbe barks and related dietary supplements. Good separation was achieved using a Waters Acquity ethylene bridged hybrid C18 column with gradient elution using 0.1% (v/v) aqueous ammonium hydroxide and 0.1% ammonium hydroxide in methanol as the mobile phases. The method can separate corynanthine from yohimbine in yohimbe bark extract, which is critical for accurate quantitation of yohimbine in yohimbe bark and related dietary supplements. Accuracy of the method was demonstrated using standard addition methods. Both intraday and interday precisions of the method were good. The method can be used without MS since yohimbine concentration in yohimbe barks and related dietary supplements are usually high enough for DAD detection, which can make it an easy and economical method for routine analysis of yohimbe barks and related dietary supplements. On the other hand, the method can be used with MS if desired for more challenging work such as biological and/or clinical studies. PMID- 26268970 TI - HPLC Method for Simultaneous Quantification of Bakuchiol and Minor Furocoumarins in Bakuchiol Extract from Psoralea corylifolia. AB - A simple, sensitive, and rapid HPLC method was developed to analyze bakuchiol and two furocoumarins (psoralen and angelicin) simultaneously in bakuchiol extracts from Psoralea corylifolia seeds. The analysis was performed within 30 min on a phenyl-hexyl column using gradient elution with a mobile phase composed of water and methanol with UV detection at 260 nm for bakuchiol and 246 nm for psoralen and angelicin. The method was validated with respect to linearity (r2>0.99 for all components), accuracy (>95% for all components), and precision (<2% RSD for both interday and intraday). Sensitivity of impurity detection in the sample was achieved as low as 0.36 and 0.31 MUg/mL for psoralen and angelicin, respectively. Therefore, the method is suitable for QC of P. corylifolia extracts and bakuchiol related samples. PMID- 26268971 TI - Simultaneous Quantification of Five Bioactive Flavonoids in High Altitude Plant Actinocarya tibetica by LC-ESI-MS/MS. AB - An LC/MS method has been developed for the simultaneous quantification of five flavonoids, i.e., mosloflavone, negletein, gardenin B, 5-methoxy-6,7 methylenedioxyflavone, and 5,6,7-trimethoxyflavone, in different ultrasound assisted solvent extracts of Actinocarya tibetica. The chromatographic separation was achieved on a Chromolith Speed ROD RP-18e column with gradient elution using methanol and 0.1% formic acid in water. The calibration curves of all five analytes showed good linearity (R2>0.991). Accuracy and precision were within the required limits. The developed method could serve as an effective method for QC of A. tibetica. The investigated compounds were determined simultaneously for the first time in A. tibetica or any other plant. PMID- 26268973 TI - A Simple LC/MS/MS Method for the Determination of Moxifloxacin N-Sulfate in Rat Plasma and Its Application in a Pharmacokinetic Study. AB - Moxifloxacin N-sulfate is one of the main metabolites of moxifloxacin in phase II metabolism mediated by sulfotransferases. In this study, a simple, rapid, and sensitive LC/MS/MS method with one-step protein precipitation with methanol was developed and validated to quantify the concentration of moxifloxacin N-sulfate in rat plasma. The chromatographic separation was accomplished by using an Agilent Extend C18 column (4.6*250 mm; 5 MUm) with a mobile phase consisting of acetonitrile and distilled water (30:70, v/v) containing 5 mM ammonium formate (pH=8.82 adjusted by ammonia) at a flow rate of 1.0 mL/min. A triple quadrupole tandem mass spectrometer with electrospray ionization source was used as a detector operated by multiple reaction monitoring in the negative-ion mode with m/z 480.2/436.3. The calibration curve was linear ranging from 2 to 200 ng/mL. The intraday and interday precision values (RSD) were less than 7.10%, and the intraday and interday accuracy values (relative error) were within -0.40 to 4.99%. Stabilities of all QC samples were within general assay acceptability criteria according to the U.S. Food and Drug Administration guidelines. No considerable matrix effect was found. A pharmacokinetic study of moxifloxacin N sulfate after a single oral dose of moxifloxacin in rats was carried out using this new method. PMID- 26268972 TI - Development of a Single Ion Pair HPLC Method for Analysis of Terbinafine, Ofloxacin, Ornidazole, Clobetasol, and Two Preservatives in a Cream Formulation: Application to In Vitro Drug Release in Topical Simulated Media-Phosphate Buffer Through Rat Skin. AB - Present work reports an HPLC method with UV detection for quantification of terbinafine, ofloxacin, ornidazole, and clobetasol in a cream formulation along with two preservatives methyl and propyl paraben. The chromatographic separation and quantification was achieved by an octyl bonded column and a gradient elution program involving an ion-pairing reagent, hexanesulfonic acid (0.2%, pH modified to 2.7 using orthophosphoric acid) and acetonitrile. The method was simple and devoid of buffer salts and therefore advantageous for system and column life. The three step gradient program was initiated with 30% (v/v) acetonitrile for the first 5 min and ramped linearly to 60% in the next 7 min. The mobile phase remained constant for the next 11 min and then concluded at 30% (v/v) of acetonitrile. Flow rate throughout was 0.8 mL/min, and all the signals were monitored at 243 nm. The method was applied for assay of a cream formulation and its in vitro permeation studies to determine the penetration profile of the four drugs and two preservatives. A marketed cream formulation was selected for the permeation study, which was carried out using a diffusion cell consisting of topical simulated media, phosphate buffer (pH=6.8) solution containing 1% sodium lauryl sulfate as a receiver medium. PMID- 26268974 TI - Isolation of Aeromonas spp. from Food Products: Emerging Aeromonas Infections and Their Significance in Public Health. AB - Aeromonas spp. are opportunistic pathogens causing a broad spectrum of human illnesses like gastroenteritis, chronic diarrhea, wound infections, peritonitis, urinary tract infections, and septicemia. Their ability to grow in foods stored in a refrigerator poses a substantial threat for human consumption. We investigated the prevalence of Aeromonas from commercial food products across Riyadh, Saudi Arabia. A total of 250 samples were randomly collected and processed for the isolation and identification of Aeromonas by morphological and biochemical means and for their identification by PCR. A total of 102 strains of Aeromonas were isolated, including 47% from raw meat samples, 34% from raw fish samples, and 18.6% from milk and dairy products; 56.8% were identified as A. hydrophila and 43.1% as A. sobria. Antibiotic susceptibility tests done revealed 100% sensitivity to chloramphenicol, colistin, ciprofloxacin, and nitrofurantoin. 16S rDNA PCR revealed the presence of the 953 bp fragment in all the strains. The present investigation suggested the occurrences of A. sobria and A. hydrophila in human consumable stored and refrigerated foods. PMID- 26268975 TI - AOAC Official MethodSM Matrix Extension Validation Study of Assurance GDSTM for the Detection of Salmonella in Selected Spices. AB - Assurance GDSTM for Salmonella Tq has been validated according to the AOAC INTERNATIONAL Methods Committee Guidelines for Validation of Microbiological Methods for Food and Environmental Surfaces for the detection of selected foods and environmental surfaces (Official Method of AnalysisSM 2009.03, Performance Tested MethodSM No. 050602). The method also completed AFNOR validation (following the ISO 16140 standard) compared to the reference method EN ISO 6579. For AFNOR, GDS was given a scope covering all human food, animal feed stuff, and environmental surfaces (Certificate No. TRA02/12-01/09). Results showed that Assurance GDS for Salmonella (GDS) has high sensitivity and is equivalent to the reference culture methods for the detection of motile and non-motile Salmonella. As part of the aforementioned validations, inclusivity and exclusivity studies, stability, and ruggedness studies were also conducted. Assurance GDS has 100% inclusivity and exclusivity among the 100 Salmonella serovars and 35 non Salmonella organisms analyzed. To add to the scope of the Assurance GDS for Salmonella method, a matrix extension study was conducted, following the AOAC guidelines, to validate the application of the method for selected spices, specifically curry powder, cumin powder, and chili powder, for the detection of Salmonella. PMID- 26268976 TI - Method Validation for the Quantitative Analysis of Aflatoxins (B1, B2, G1, and G2) and Ochratoxin A in Processed Cereal-Based Foods by HPLC with Fluorescence Detection. AB - Modified AOAC 991.31 and AOAC 2000.03 methods for the simultaneous determination of total aflatoxins (AFs), aflatoxin B1, and ochratoxin A (OTA) in processed cereal-based foods by RP-HPLC coupled with fluorescence detection were validated. A KOBRA(r) Cell derivatization system was used to analyze total AFs. One of the modifications was the extraction procedure of mycotoxins. Both AFs and OTA were extracted with methanol-water (75+25, v/v) and purified with an immunoaffinity column before HPLC analysis. The modified methods were validated by measuring the specificity, selectivity, linearity, sensitivity, accuracy, repeatability, reproducibility, recovery, LOD, and LOQ parameters. The validated methods were successfully applied for the simultaneous determination of mycotoxins in 81 processed cereal-based foods purchased in Turkey. These rapid, sensitive, simple, and validated methods are suitable for the simultaneous determination of AFs and OTA in the processed cereal-based foods. PMID- 26268977 TI - Comparison of Column Solid-Phase Extraction Procedures for Spectrophotometric Determination of E129 (Allura Red) in Foodstuff, Pharmaceutical, and Energy Drink Samples. AB - Two novel spectrophotometric determination procedures based on retention of Allura Red onto Amberlite XAD-1180 and XAD-16 resins for its preconcentration, purification, and separation were developed. Analytical parameters of the methods including pH, eluent type, sample volume, and sample and eluent flow rates, were investigated and optimized. Interference effects of some cations, anions, and widely used food dyes were also investigated. Detection limits of the two methods were found to be 1.2 and 1.5 MUg/L for XAD-1180 and XAD-16 columns, respectively, under optimum conditions. Linear calibration curve ranges of the methods were 0.4 8.0 and 0.5-6.0 MUg/mL of Allura Red for XAD-1180 and XAD-16 resins, respectively. Preconcentration factors were found as 80 for both the XAD-1180 and XAD-16 columns using maximum sample volume and minimum eluent volume. RSDs of the methods were below 6% throughout all experiments. All absorbance measurements were performed at 506 nm. Validations of the methods were performed comparatively with determination of the Allura Red contents of some foodstuff, pharmaceutical, and energy drink samples. Allura Red concentrations in investigated solid and liquid samples ranged from 298 to 501 MUg/g and 53.8 to 508 MUg/mL, respectively. Satisfactory results were obtained from the real samples analysis. Allura Red contents of samples were determined to be highly similar using the two extraction methods. Comparisons of the methods were performed by analysis of Allura Red contents of the real samples. In addition to analytical parameters, adsorption isotherm studies were performed for the two kinds of Amberlite resins. It was observed that developed methods fit the linear form of the Freundlich adsorption isotherm model. All of the experimental results suggested that the developed SPE procedures are suitable for separation, preconcentration, and determination of Allura Red in solid and liquid matrixes. PMID- 26268978 TI - Simultaneous Determination of 10 Ultratrace Elements in Infant Formula, Adult Nutritionals, and Milk Products by ICP/MS After Pressure Digestion: Single Laboratory Validation. AB - A single-laboratory validation (SLV) is presented for the simultaneous determination of 10 ultratrace elements (UTEs) including aluminum (Al), arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), mercury (Hg), molybdenum (Mo), lead (Pb), selenium (Se), and tin (Sn) in infant formulas, adult nutritionals, and milk based products by inductively coupled plasma (ICP)/MS after acidic pressure digestion. This robust and routine multielemental method is based on several official methods with modifications of sample preparation using either microwave digestion or high pressure ashing and of analytical conditions using ICP/MS with collision cell technology. This SLV fulfills AOAC method performance criteria in terms of linearity, specificity, sensitivity, precision, and accuracy and fully answers most international regulation limits for trace contaminants and/or recommended nutrient levels established for 10 UTEs in targeted matrixes. PMID- 26268979 TI - Optimized Dispersive Liquid-Liquid Microextraction Method and High Performance Liquid Chromatography with Ultraviolet Detection for Simultaneous Determination of Sorbic and Benzoic Acids and Evaluation of Contamination of These Preservatives in Iranian Foods. AB - A rapid, simple, and sensitive dispersive liquid-liquid microextraction procedure followed by HPLC-UV was applied to determine the benzoate and sorbate in foods. The method was optimized for some variables including extraction solvent type and volume, dispersing solvent type and volume, and the effects of salt and pH. Optimum conditions were determined as follows: sample volume, 5 mL; extraction solvent (chloroform) volume, 250 MUL; disperser solvent (acetone) volume, 1.2 mL; NaCl amount, 0.75 g/5 mL at pH 4. Sixty samples were analyzed, including 15 doogh, 15 fruit juice, 15 cookie, and 15 tomato paste; benzoic acid was detected in 57 samples (95%) at levels up to 448.1 MUg/mL and sorbic acid in 31 samples (51.6%) at levels up to 1369 MUg/mL. Under the optimum experimental conditions, the LOD and LOQ were determined as 0.1 and 0.5 MUg/mL for benzoate and 0.08 and 0.3 MUg/mL for sorbate, respectively. The results showed that these preservatives are commonly used at high levels in yogurt drinks (dooghs) and cookies. Also, the concentration of benzoic acid that was detected in the tomato paste and fruit juice samples was low but may affect children and sensitive persons. PMID- 26268980 TI - Analysis of Nucleotide 5'-Monophosphates in Infant Formulas by HPLC-UV: Collaborative Study, Final Action 2011.20. AB - A collaborative study was conducted on AOAC First Action Method 2011.20: 5' Mononucleotides in Infant Formula and Adult/Pediatric Nutritional Formula. After the successful analysis of National Institute of Standards and Technology (NIST) 1849a Standard Reference Material (SRM) as a practice sample, 12 laboratories participated in the analysis of duplicate samples of six different infant formula products. The samples were dissolved in high-salt solution to inhibit protein and fat interactions, with the nucleotides [uridine 5'-monophosphate (UMP), inosine 5'-monophosphate (IMP), adenosine 5'-monophosphate (AMP), guanosine 5' monophosphate (GMP), and cytidine 5'-monophosphate (CMP)] separated from the sample matrix by strong-anion exchange SPE, followed by chromatographic analysis using a C18 stationary phase with gradient elution, UV detection, and quantitation by an internal standard technique using thymidine 5'-monophosphate. For nucleotide-supplemented products, precision is within the Standard Method Performance RequirementsSM (SMPR) 2011.008 target reproducibility limit of <=11%, with the reproducibility RSD (RSDR) estimated at 7.1-8.7% for CMP, 7.9-9.0% for UMP, 2.8-7.7% for GMP, 5.5-10.3% for IMP, and 2.7-6.2% for AMP, and Horwitz ratio (HorRat) values of 0.9-1.0 for CMP, 0.9-1.0 for UMP, 0.3-0.7 for GMP, 0.6-1.0 for IMP, and 0.3-0.7 for AMP. PMID- 26268981 TI - Evaluation of 3MTM Molecular Detection Assay (MDA) Listeria monocytogenes for the Detection of Listeria monocytogenes in Selected Foods and Environmental Surfaces: Collaborative Study, First Action 2014.07. AB - The 3MTM Molecular Detection Assay (MDA) Listeria monocytogenes combines isothermal amplification and bioluminescence to detect Listeria monocytogenes with high specificity and efficiency in select foods and environmental samples. The 3M MDA Listeria monocytogenes method was evaluated using an unpaired study design in a multilaboratory collaborative study to the U.S. Department of Agriculture, Food Safety and Inspection Service Microbiology Laboratory Guidebook 8.09 (2011) Isolation and Identification of Listeria monocytogenes from Red Meat, Poultry, and Egg Products and Environmental Samples for deli turkey, and the AOAC Official Method of Analysis(SM) 993.12 Listeria monocytogenes in Milk and Dairy Products for full-fat (4% milk fat) cottage cheese following the current AOAC guidelines. A total of 16 laboratories located in the continental United States and Canada participated in this collaborative study. For deli turkey, 125 g test portions were evaluated using heat-stressed cells by each method. For full-fat cottage cheese, 25 g test portions were evaluated using nonheat-stressed cells. Each matrix had three inoculation levels: an uninoculated control level (0 CFU/test portion), and two levels artificially contaminated with L. monocytogenes, a low inoculum level (0.2-2 CFU/test portion) and a high inoculum level (2-5 CFU/test portion). In total, 1584 unpaired replicate samples were analyzed. Statistical analysis was conducted according to the probability of detection (POD) model. Results obtained for the low inoculum level full-fat cottage cheese test portions produced a difference in cross-laboratory POD (dLPOD) value of -0.08 with a 95% confidence interval (CI) of (-0.20, 0.05). For the low-level deli turkey test portions, a dLPOD value of -0.02 with a 95% CI of (-0.14, 0.11) was obtained. PMID- 26268982 TI - Evaluation of 3MTM Molecular Detection Assay (MDA) Listeria for the Detection of Listeria species in Selected Foods and Environmental Surfaces: Collaborative Study, First Action 2014.06. AB - The 3MTM Molecular Detection Assay (MDA) Listeria is used with the 3M Molecular Detection System for the detection of Listeria species in food, food-related, and environmental samples after enrichment. The assay utilizes loop-mediated isothermal amplification to rapidly amplify Listeria target DNA with high specificity and sensitivity, combined with bioluminescence to detect the amplification. The 3M MDA Listeria method was evaluated using an unpaired study design in a multilaboratory collaborative study and compared to the AOAC Official Method of AnalysisSM (OMA) 993.12 Listeria monocytogenes in Milk and Dairy Products reference method for the detection of Listeria species in full-fat (4% milk fat) cottage cheese (25 g test portions). A total of 15 laboratories located in the continental United States and Canada participated. Each matrix had three inoculation levels: an uninoculated control level (0 CFU/test portion), and two levels artificially contaminated with Listeria monocytogenes, a low inoculum level (0.2-2 CFU/test portion) and a high inoculum level (2-5 CFU/test portion) using nonheat-stressed cells. In total, 792 unpaired replicate portions were analyzed. Statistical analysis was conducted according to the probability of detection (POD) model. Results obtained for the low inoculum level test portions produced a difference in cross-laboratory POD value of -0.07 with a 95% confidence interval of (-0.19, 0.06). No statistically significant differences were observed in the number of positive samples detected by the 3M MDA Listeria method versus the AOAC OMA method. PMID- 26268983 TI - A Method Detection Limit for Bacillus anthracis Spores in Water Using an Automated Waterborne Pathogen Concentrator. AB - The method detection limit (MDL, 99% chance of detecting a positive result in a single replicate), as per the United States Code of Federal Regulations, was determined for a protocol using an ultrafiltration based automated waterborne pathogen concentration device. Bacillus anthracis Sterne strain spores were seeded at low levels into 100 L reagent water samples. Suspect colonies were confirmed through morphological, chemical, and genetic tests. Samples of 100 L (n=14) of reagent water were seeded with five B. anthracis CFUs each. To confirm the estimated detection limit, a second set (n=19) of 100 L reagent water samples were seeded at a higher level (7 CFUs). The second estimate of the MDL could not be pooled with the first, due to significant difference in variance. A third trial (n=7) seeded with 10 CFUs produced an estimate of the MDL that could be pooled with the higher previous estimate. Another trial consisting of eight 100 L samples of tap water were seeded with approximately 7 CFUs. Recovery in these samples was not significantly different from the pooled MDL. Theoretically a concentration of 4.6 spores/100 L would be required for detection 95% of the time, based on a Poisson distribution. The calculated pooled MDL, based on experimental data was approximately 6 B. anthracis CFU/100 L (95% confidence interval 4.8 to 8.4). Detection at this level was achieved in municipal water samples. PMID- 26268985 TI - Standard Method Performance Requirements(SM) and corresponding AOAC First and Final Action Official MethodsSM. PMID- 26268984 TI - TLC-Direct Bioautography as a Bioassay Guided Method for Investigation of Antibacterial Compounds in Hypericum perforatum L. AB - Fast high-throughput TLC-direct bioautography (DB) is an effect-directed analysis method that enables searching for biologically active (e.g., antimicrobial) substances in complex mixtures like plant extracts. The principle of the method is that separation and detection of biological properties of given mixture components is performed directly on a TLC plate. In searching for antibacterial activity, the developed plate is immersed in a bacterial broth, and bacteria grow directly on its layer during a proper incubation time. Inhibition zones are formed in places where antimicrobial components are located. The active compounds can be further identified using spectroscopic techniques. The aim of our study was investigation of plant components of Hypericum perforatum L. tincture by TLC DB using nine bacterial strains: Micrococcus luteus, Bacillus subtilis, Escherichia coli, Staphylococcus aureus, methicillin-resistant S. aureus, S. epidermidis, Pseudomonas syringae pv. maculicola, Xanthomonas campestris pv. vesicatoria, and Aliivibrio fischeri. Compounds showing the widest range of antimicrobial activity were isolated using semipreparative TLC and identified as apigenin, 3,8'-biapigenin, quercetin, kaempferol, and linolenic acid by TLC, HPLC diode array detection, and HPLC/MS/MS techniques. PMID- 26268987 TI - Soya products and serum lipids: a meta-analysis of randomised controlled trials. AB - Soya proteins and isoflavones have been reported to exert beneficial effects on the serum lipid profile. More recently, this claim is being challenged. The objective of this study was to comprehensively examine the effects of soya consumption on the lipid profile using published trials. A detailed literature search was conducted via MEDLINE (from 2004 through February 2014), CENTRAL (The Cochrane Controlled Clinical Trials Register) and ClinicalTrials.gov for randomised controlled trials assessing the effects of soya on the lipid profile. The primary effect measure was the difference in means of the final measurements between the intervention and control groups. In all, thirty-five studies (fifty comparisons) were included in our analyses. Treatment duration ranged from 4 weeks to 1 year. Intake of soya products resulted in a significant reduction in serum LDL-cholesterol concentration, -4.83 (95% CI -7.34, -2.31) mg/dl, TAG, 4.92 (95% CI -7.79, -2.04) mg/dl, and total cholesterol (TC) concentrations, 5.33 (95% CI -8.35, -2.30) mg/dl. There was also a significant increase in serum HDL-cholesterol concentration, 1.40 (95% CI 0.58, 2.23) mg/dl. The I2 statistic ranged from 92 to 99%, indicating significant heterogeneity. LDL reductions were more marked in hypercholesterolaemic patients, -7.47 (95% CI -11.79, -3.16) mg/dl, than in healthy subjects, -2.96 (95% CI -5.28, -0.65) mg/dl. LDL reduction was stronger when whole soya products (soya milk, soyabeans and nuts) were used as the test regimen, -11.06 (95% CI -15.74, -6.37) mg/dl, as opposed to when 'processed' soya extracts, -3.17 (95% CI -5.75, -0.58) mg/dl, were used. These data are consistent with the beneficial effects of soya proteins on serum LDL, HDL, TAG and TC concentrations. The effect was stronger in hypercholesterolaemic subjects. Whole soya foods appeared to be more beneficial than soya supplementation, whereas isoflavone supplementation had no effects on the lipid profile. PMID- 26268986 TI - Slow-growing cells within isogenic populations have increased RNA polymerase error rates and DNA damage. AB - Isogenic cells show a large degree of variability in growth rate, even when cultured in the same environment. Such cell-to-cell variability in growth can alter sensitivity to antibiotics, chemotherapy and environmental stress. To characterize transcriptional differences associated with this variability, we have developed a method--FitFlow--that enables the sorting of subpopulations by growth rate. The slow-growing subpopulation shows a transcriptional stress response, but, more surprisingly, these cells have reduced RNA polymerase fidelity and exhibit a DNA damage response. As DNA damage is often caused by oxidative stress, we test the addition of an antioxidant, and find that it reduces the size of the slow-growing population. More generally, we find a significantly altered transcriptome in the slow-growing subpopulation that only partially resembles that of cells growing slowly due to environmental and culture conditions. Slow-growing cells upregulate transposons and express more chromosomal, viral and plasmid-borne transcripts, and thus explore a larger genotypic--and so phenotypic--space. PMID- 26268988 TI - Comparing equals when evaluating immunotherapy with different doses and fractions of radiation therapy. PMID- 26268989 TI - Evidence that the endosomal sorting complex required for transport-II (ESCRT-II) is required for efficient human immunodeficiency virus-1 (HIV-1) production. AB - BACKGROUND: Egress of a number of different virus species from infected cells depends on proteins of the endosomal sorting complexes required for transport (ESCRT) pathway. HIV has also hijacked this system to bud viruses outward from the cell surface. How ESCRT-I activates ESCRT-III in this process remains unclear with conflicting published evidence for the requirement of ESCRT-II which fulfils this role in other systems. We investigated the role of ESCRT-II using knockdown mediated by siRNA and shRNA, mutants which prevent ESCRT-I/ESCRT-II interaction and a CRISPR/Cas9 EAP45 knockout cell line. RESULTS: Depletion or elimination of ESCRT-II components from an HIV infected cell produces two distinct effects. The overall production of HIV-1 Gag is reduced leading to a diminished amount of intracellular virion protein. In addition depletion of ESCRT-II produces an effect similar to that seen when ESCRT-I and -III components are depleted, that of a delayed Gag p26 to p24 +p2 cleavage associated with a reduction in export of virion particles and a visible reduction in budding efficiency in virus producing cells. Mutants that interfere with ESCRT-I interacting with ESCRT-II similarly reduce virus export. The export defect is independent of the decrease in overall Gag production. Using a mutant virus which cannot use the ALIX mediated export pathway exacerbates the decrease in virus export seen when ESCRT-II is depleted. ESCRT-II knockdown does not lead to complete elimination of virus release suggesting that the late domain role of ESCRT-II is required for optimal efficiency of viral budding but that there are additional pathways that the virus can employ to facilitate this. CONCLUSION: ESCRT-II contributes to efficient HIV virion production and export by more than one pathway; both by a transcriptional or post transcriptional mechanism and also by facilitating efficient virus export from the cell through interactions with other ESCRT components. PMID- 26268990 TI - Diversity of the cell-wall associated genomic island of the archaeon Haloquadratum walsbyi. AB - BACKGROUND: Haloquadratum walsbyi represents up to 80% of cells in NaCl-saturated brines worldwide, but is notoriously difficult to maintain under laboratory conditions. In order to establish the extent of genetic diversity in a natural population of this microbe, we screened a H. walsbyi enriched metagenomic fosmid library and recovered seven novel version of its cell-wall associated genomic island. The fosmid inserts were sequenced and analysed. RESULTS: The novel cell wall associated islands delineated two major clades within H. walsbyi. The islands predominantly contained genes putatively involved in biosynthesis of surface layer, genes encoding cell surface glycoproteins and genes involved in envelope formation. We further found that these genes are maintained in the population and that the diversity of this region arises through homologous recombination but also through the action of mobile genetic elements, including viruses. CONCLUSIONS: The population of H. walsbyi in the studied saltern brine is composed of numerous clonal lineages that differ in surface structures including the cell wall. This type of variation probably reflects a number of mechanisms that minimize the infection rate of predating viruses. PMID- 26268991 TI - Genotoxicity evaluation of Oryeong-san water extract using in vitro and in vivo tests. AB - BACKGROUND: Oryeong-san, a mixture of five herbal plants, is a well-known therapy for renal-associated diseases such as those manifesting edema, dysuria, and oliguria. METHODS: In the present study, we investigatee the potential genotoxic effects of a water extract of Oryeong-san (ORSE) in three mutagenicity assays (an in vitro bacterial reverse mutation assay (Ames test) with Salmonella typhimurium and Escherichia coli strains, an in vitro mammalian chromosomal aberration test using Chinese hamster lung cells, and an in vivo micronucleus test using ICR mice bone marrow). RESULTS: ORSE showed no genotoxicity in the Ames test up to 5000 MUg/plate; the in vitro chromosome aberration test showed no significant structural aberrations with and without the S9 mix up to 5000 MUg/mL, or the in vivo micronucleus test up to 2000 mg/kg body weight. CONCLUSIONS: In conclusion, under the current test conditions, ORSE seems safe for use; however, other genotoxicity tests (e.g. sister-chromatid exchange or Comet) or chronic toxicity tests are warranted. PMID- 26268992 TI - Plasmid carriage can limit bacteria-phage coevolution. AB - Coevolution with bacteriophages is a major selective force shaping bacterial populations and communities. A variety of both environmental and genetic factors has been shown to influence the mode and tempo of bacteria-phage coevolution. Here, we test the effects that carriage of a large conjugative plasmid, pQBR103, had on antagonistic coevolution between the bacterium Pseudomonas fluorescens and its phage, SBW25phi2. Plasmid carriage limited bacteria-phage coevolution; bacteria evolved lower phage-resistance and phages evolved lower infectivity in plasmid-carrying compared with plasmid-free populations. These differences were not explained by effects of plasmid carriage on the costs of phage resistance mutations. Surprisingly, in the presence of phages, plasmid carriage resulted in the evolution of high frequencies of mucoid bacterial colonies. Mucoidy can provide weak partial resistance against SBW25phi2, which may have limited selection for qualitative resistance mutations in our experiments. Taken together, our results suggest that plasmids can have evolutionary consequences for bacteria that go beyond the direct phenotypic effects of their accessory gene cargo. PMID- 26268993 TI - Phenotype-environment matching in sand fleas. AB - Camouflage is perhaps the most widespread anti-predator strategy in nature, found in numerous animal groups. A long-standing prediction is that individuals should have camouflage tuned to the visual backgrounds where they live. However, while several studies have demonstrated phenotype-environment associations, few have directly shown that this confers an improvement in camouflage, particularly with respect to predator vision. Here, we show that an intertidal crustacean, the sand flea (Hippa testudinaria), has coloration tuned to the different substrates on which it occurs when viewed by potential avian predators. Individual sand fleas from a small, oceanic island (Ascension) matched the colour and luminance of their own beaches more closely than neighbouring beaches to a model of avian vision. Based on past work, this phenotype-environment matching is likely to be driven through ontogenetic changes rather than genetic adaptation. Our work provides some of the first direct evidence that animal coloration is tuned to provide camouflage to prospective predators against a range of visual backgrounds, in a population of animals occurring over a small geographical range. PMID- 26268994 TI - Feedback of trees on nitrogen mineralization to restrict the advance of trees in C4 savannahs. AB - Remote sensing studies suggest that savannahs are transforming into more tree dominated states; however, progressive nitrogen limitation could potentially retard this putatively CO2-driven invasion. We analysed controls on nitrogen mineralization rates in savannah by manipulating rainfall and the cover of grass and tree elements against the backdrop of the seasonal temperature and rainfall variation. We found that the seasonal pattern of nitrogen mineralization was strongly influenced by rainfall, and that manipulative increases in rainfall could boost mineralization rates. Additionally, mineralization rates were considerably higher on plots with grasses and lower on plots with trees. Our findings suggest that shifting a savannah from a grass to a tree-dominated state can substantially reduce nitrogen mineralization rates, thereby potentially creating a negative feedback on the CO2-induced invasion of savannahs by trees. PMID- 26268995 TI - Prediction of Core Body Temperature from Multiple Variables. AB - This paper aims to improve the prediction of rectal temperature (T re) from insulated skin temperature (T is) and micro-climate temperature (T mc) previously reported (Richmond et al., Insulated skin temperature as a measure of core body temperature for individuals wearing CBRN protective clothing. Physiol Meas 2013; 34:1531-43.) using additional physiological and/or environmental variables, under several clothing and climatic conditions. Twelve male (25.8+/-5.1 years; 73.6+/ 11.5kg; 178+/-6cm) and nine female (24.2+/-5.1 years; 62.4+/-11.5kg; 169+/-3cm) volunteers completed six trials, each consisting of two 40-min periods of treadmill walking separated by a 20-min rest, wearing permeable or impermeable clothing, under neutral (25 degrees C, 50%), moderate (35 degrees C, 35%), and hot (40 degrees C, 25%) conditions, with and without solar radiation (600W m( 2)). Participants were measured for heart rate (HR) (Polar, Finland), skin temperature (T s) at 11 sites, T is (Grant, Cambridge, UK), and breathing rate (f) (Hidalgo, Cambridge, UK). T mc and relative humidity were measured within the clothing. T re was monitored as the 'gold standard' measure of T c for industrial or military applications using a 10cm flexible probe (Grant, Cambridge, UK). A stepwise multiple regression analysis was run to determine which of 30 variables (T is, T s at 11 sites, HR, f, T mc, temperature, and humidity inside the clothing front and back, body mass, age, body fat, sex, clothing, Thermal comfort, sensation and perception, and sweat rate) were the strongest on which to base the model. Using a bootstrap methodology to develop the equation, the best model in terms of practicality and validity included T is, T mc, HR, and 'work' (0 = rest; 1 = exercise), predicting T re with a standard error of the estimate of 0.27 degrees C and adjusted r (2) of 0.86. The sensitivity and specificity for predicting individuals who reached 39 degrees C was 97 and 85%, respectively. Insulated skin temperature was the most important individual parameter for the prediction of T re. This paper provides novel information about the viability of predicting T c under a wide range of conditions, using predictors which can practically be measured in a field environment. PMID- 26268996 TI - Stromal expression of VEGF-A and VEGFR-2 in prostate tissue is associated with biochemical and clinical recurrence after radical prostatectomy. AB - BACKGROUND: There is probably significant overtreatment of patients with prostate cancer due to a lack of sufficient diagnostic tools to predict aggressive disease. Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are potent mediators of angiogenesis and tumor proliferation, but have been examined to a limited extent in large prostate cancer studies. Meanwhile, recent promising results on VEGFR-2 inhibition have highlighted their importance, leading to the need for further investigations regarding their expression and prognostic impact. DESIGN: Using tissue microarray and immunohistochemistry, the expression of VEGFs (VEGF-A and VEGF-C) and their receptors (VEGFR-2 and VEGFR-3) were measured in neoplastic tissue and corresponding stroma from radical prostatectomy specimens in 535 Norwegian patients. Their expression was evaluated semiquantatively and associations with event-free survival were calculated. RESULTS: High expression of VEGFR-2 in either stroma or epithelium was independently associated with a higher incidence of prostate cancer relapse (HR = 4.56, P = 0.038). A high combined expression of either VEGF-A, VEGFR-2 or both in stroma was independently associated with a higher incidence of biochemical failure (HR = 1.77, P = 0.011). CONCLUSIONS: This large study highlights the prognostic importance of VEGF-A and VEGFR-2 stromal expression. Analyses of these biomarkers may help distinguish which patients will benefit from radical treatment. Together with previous studies showing efficiency of targeting VEGFR-2 in prostate cancer, this study highlights its potential as a target for therapy, and may aid in future selection of prostate cancer patients for novel anti angiogenic treatment. PMID- 26268998 TI - Urologic cancer in Japan: role of Japan at the frontier of issues in Asia. AB - The characteristics of urological cancer in Japan can be summarized in the following points. (i) As the onset of this type of cancer is typically seen in elderly patients, it is becoming a major social issue in Japan that has already become an aging society. (ii) Many diverse treatment methods are available and a response is required that prioritizes quality of life. (iii) Although vigorous research and development efforts into new drugs are being carried out on a global level, resulting in beneficial medical agents becoming more readily available, unless concepts relating to cost vs. effectiveness are further developed and there is a real risk that medical systems and structures in their current form will become unsustainable. (iv) Although at the current point there are no original large-scale clinical trials being conducted in Asia, Japan has a wealth of experience of participating in many international joint clinical trials and it is therefore an urgent and pressing challenge to organize joint clinical trials in Asia and amass a body of knowledge that is unique to Asia. In view of this current situation and given Japan's position at the frontier of issues, it is important for Japan to take the initiative in Asia in cooperating with other Asian nations in efforts to resolve and overcome various challenges. PMID- 26268997 TI - Alterations in lipid transfers to HDL associated with the presence of coronary artery disease in patients with type 2 diabetes mellitus. AB - BACKGROUND: We previously showed that unesterified-cholesterol transfer to high density lipoprotein (HDL), a crucial step in cholesterol esterification and role in reverse cholesterol transport, was diminished in non-diabetic patients with coronary artery disease (CAD). The aim was to investigate whether, in patients with type 2 diabetes mellitus (T2DM), the occurrence of CAD was also associated with alterations in lipid transfers and other parameters of plasma lipid metabolism. METHODS: Seventy-nine T2DM with CAD and 76 T2DM without CAD, confirmed by cineangiography, paired for sex, age (40-80 years), BMI and without statin use, were studied. In vitro transfer of four lipids to HDL was performed by incubating plasma of each patient with a donor emulsion containing radioactive lipids during 1 h at 37 degrees C. Lipids transferred to HDL were measured after chemical precipitation of non-HDL fractions and the emulsion. Results are expressed as % of total radioactivity of each lipid in HDL. RESULTS: In T2DM + CAD, LDL-cholesterol and apo B were higher than in T2DM. T2DM + CAD also showed diminished transfer to HDL of unesterified cholesterol (T2DM + CAD = 7.6 +/- 1.2; T2DM = 8.2 +/- 1.5%, p < 0.01) and of cholesteryl-esters (4.0 +/- 0.6 vs 4.3 +/- 0.7, p < 0.01). Unesterified cholesterol in the non-HDL serum fraction was higher in T2DM + CAD (0.93 +/- 0.20 vs 0.85 +/- 0.15, p = 0.02) and CETP concentration was diminished (2.1 +/- 1.0 vs 2.5 +/- 1.1, p = 0.02). Lecithin-cholesterol acyltransferase activity, HDL size and lipid composition were equal. CONCLUSION: Reduction in T2DM + CAD of cholesterol transfer to HDL may impair cholesterol esterification and reverse cholesterol transport and altogether with simultaneous increased plasma unesterified cholesterol may facilitate CAD development in T2DM. PMID- 26268999 TI - Assessment of the effect of cigarette smoking on regional brain volumes and lesion load in patients with clinically isolated syndrome. AB - PURPOSE: Smoking has been associated with an increased risk of developing multiple sclerosis, disease progression and clinical disability. We detected the effects of smoking on regional brain volumes and lesion load in patients with clinically isolated syndrome using quantitative magnetic resonance imaging. MATERIALS AND METHODS: Smoker patients (n = 16), smoker healthy controls (n = 13), non-smoker patients (n = 17) and non-smoker healthy controls (n = 14) underwent magnetic resonance imaging and neocortical volumes were measured. Lesion load was calculated in terms of number and volume of white matter hyperintensities. RESULTS: Smoking was associated with increased gray matter volumes in several regions of the brain. A tendency towards greater lesion load in smoker patients was found. Smoking duration was significantly negatively correlated with intracranial volume and left hemisphere cortical gray matter volume. There was no relationship between regional brain volumes and clinical disability scores, lesion load duration of the disease and degree of smoking exposure. CONCLUSIONS: Clinically isolated syndrome related regional brain atrophy might vary in extent and severity with smoking. Despite increased lesion load, less cortical and deep gray matter damage with a possible neuroprotective effect occurs in smoking. PMID- 26269000 TI - Synergistic effects of gene polymorphisms of the renin-angiotensin-aldosterone system on essential hypertension in Kazakhs in Xinjiang. AB - OBJECTIVE: To assess the synergistic effects of gene polymorphisms of the renin angiotensin-aldosterone system (RAAS) on essential hypertension (EH) in Kazakhs in Xinjiang. METHODS: A cross-sectional case-control association study was conducted in 52 1 hypertensive and 623 normotensive subjects of Kazakh ethnicity on eight common single nucleotide polymorphisms (SNPs) interspersed over five genes of the RAAS. SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Interactions among the SNPs were analyzed by the multifactor dimensionality reduction method (MDR). RESULTS: In single-locus analysis, subjects with AGT -6G, ACE D, and CYP11B2 -344C had increased susceptibility to EH (OR: 1.249; 1.425; 1.201). When subgrouped by sex, males with the t allele of REN Taq I had decreased risk for EH (OR: 0.529), and those with AGT -6G and CYP11B2 -344 C had increased risk for EH (OR: 1.498; 1.449). In females, carrying ACE D increased the risk for EH. (OR: 1.327). In six AGT haplotypes, H1 was protective, while H3 increased susceptibility to EH (OR: 0.683; 2.025). Interaction analysis by MDR showed that there was a strong synergistic effect between ACE I/D and CY11B2 (T-344C) and a moderate interaction between both ACE I/D and CY11B2 T-344C and AGT A-6G. CONCLUSIONS: There was a strong synergistic effect between ACE I/D and CY11B2 T-344C and a moderate effect between both ACE I/D and CY11B2 T-344C and AGT A-6G. AGT -6G, ACE D, and CY11B2 344C increased susceptibility to EH. REN Taq I, AGT -6G, CY11B2 -344 C and ACE D were associated with male and female EH, respectively. H1 and H3 of AGT were protective and risk haplotypes, respectively. PMID- 26269001 TI - Pulse pressure and cardiovascular risk in diseased patients. PMID- 26269002 TI - Effects of Pioglitazone for Secondary Stroke Prevention in Patients with Impaired Glucose Tolerance and Newly Diagnosed Diabetes: The J-SPIRIT Study. AB - AIM: Prediabetes is an independent risk factor for future stroke. However, no effective treatment has yet been established for the recurrence of stroke in patients with prediabetes. Here we investigated the effects of pioglitazone, a potent peroxisome proliferator-activated receptor-gamma agonist, for the reduction of recurrent stroke in patients with prediabetes. METHODS: Participants were patients who had a symptomatic ischemic stroke or transient ischemic attack (TIA) without a history of type 2 diabetes mellitus and who were diagnosed to have IGT or newly diagnosed diabetes by a 75-g oral glucose tolerance test. These patients were randomized to either receive or not receive pioglitazone. The primary endpoint was a recurrence of ischemic stroke. RESULTS: A total of 120 patients were enrolled in the study. Sixty-three patients received pioglitazone and 57 were enrolled in the control group that did not receive pioglitazone. The majority of patients (68.3%) were prescribed 15 mg of pioglitazone, while the remaining patients (31.7%) were treated with 30 mg of pioglitazone. Over a median follow-up period of 2.8 years, treatment with pioglitazone was found to be associated with a lower rate of the primary endpoint (recurrence of stroke) than that observed in the control group [event rate=4.8% pioglitazone vs 10.5% control, hazard ratio=0.62, 95% confidence interval 0.13-2.35, p=0.49]. However, differences were not statistically significant. CONCLUSIONS: While this study was too underpowered to determine the effect of pioglitazone, the result failed to show beneficial effects in patients of ischemic stroke or TIA with impaired glucose tolerance and newly diagnosed diabetes. PMID- 26269004 TI - Unexpectedly High Prevalence of Acquired von Willebrand Syndrome in Patients with Severe Aortic Stenosis as Evaluated with a Novel Large Multimer Index. AB - AIM: Severe gastrointestinal bleeding sometimes occurs in patients with aortic stenosis (AS), known as Heyde's syndrome. This syndrome is thought to be caused by acquired von Willebrand syndrome and is characterized by reduced large von Willebrand factor (vWF) multimers. However, the relationship between the severity of AS and loss of large vWF multimers is unclear. METHODS: We examined 31 consecutive patients with severe AS. Quantitative evaluation for loss of large vWF multimers was performed using the conventional large vWF ratio and novel large vWF multimer index. This novel index was defined as the ratio of large multimers of patients to those of controls. RESULTS: Loss of large vWF multimers, defined as the large vWF multimer index <80%, was detected in 21 patients (67.7%). The large vWF multimer ratio and the large vWF multimer index were inversely correlated with the peak aortic gradient (R = -0.58, p=0.0007, and R= 0.64, p<0.0001, respectively). Anemia defined as hemoglobin <9.0 g/dl was observed in 12 patients (38.7%), who were regarded as Heyde's syndrome. Aortic valve replacement was performed in 7 of these patients, resulting in the improvement of anemia in all patients from a hemoglobin concentration of 7.5+/ 1.0 g/dl preoperatively to 12.4+/-1.3 g/dl postoperatively (p<0.0001). CONCLUSIONS: Acquired von Willebrand syndrome may be a differential diagnosis in patients with AS with anemia. The prevalence of AS-associated acquired von Willebrand syndrome is higher than anticipated. PMID- 26269005 TI - Sulphate production by Paracoccus pantotrophus ATCC 35512 from different sulphur substrates: sodium thiosulphate, sulphite and sulphide. AB - One of the problems in waste water treatment plants (WWTPs) is the increase in emissions of hydrogen sulphide (H2S), which can cause damage to the health of human populations and ecosystems. To control emissions of this gas, sulphur oxidizing bacteria can be used to convert H2S to sulphate. In this work, sulphate detection was performed by spectrophotometry, ion chromatography and atomic absorption spectrometry, using Paracoccus pantotrophus ATCC 35512 as a reference strain growing in an inorganic broth supplemented with sodium thiosulphate (Na2S2O3.5H2O), sodium sulphide (Na2S) or sodium sulphite (Na2SO3), separately. The strain was metabolically competent in sulphate production. However, it was only possible to observe significant differences in sulphate production compared to abiotic control when the inorganic medium was supplemented with sodium thiosulphate. The three methods for sulphate detection showed similar patterns, although the chromatographic method was the most sensitive for this study. This strain can be used as a reference for sulphate production in studies with sulphur oxidizing bacteria originating from environmental samples of WWTPs. PMID- 26269003 TI - Association between Pulse Wave Velocity and Coronary Artery Calcification in Japanese men. AB - AIM: Pulse wave velocity (PWV) is a simple and valid clinical method for assessing arterial stiffness. Coronary artery calcification (CAC) is an intermediate stage in the process leading to overt cardiovascular disease (CVD) and an established determinant of coronary artery disease. This study aimed to examine the association between PWV and CAC in a population-based sample of Japanese men. METHODS: This is a cross-sectional study of 986 randomly selected men aged 40-79 years from Shiga, Japan. CVD-free participants were examined from 2006 to 2008. Brachial-ankle PWV (baPWV) was measured using an automatic waveform analyzer. CAC was assessed using computed tomography. Agatston scores >= 10 were defined as the presence of CAC. RESULTS: Prevalence of CAC progressively increased with rising levels of baPWV: 20.6%, 41.7%, 56.3%, and 66.7% across baPWV quartiles < 1378, 1378-1563, 1564-1849, and > 1849 cm/s (P < 0.001 for trend). Associations remained significant after adjusting for age and other factors, including body mass index, systolic blood pressure, pulse rate, total and high-density lipoprotein cholesterol, hemoglobin A1c, drinking, smoking and exercise status, and the use of medication to treat hypertension, dyslipidemia and diabetes (P=0.042 for trend). The optimal cutoff level of baPWV to detect CAC was 1612 cm/s using receiver operating characteristic curve analysis. CONCLUSIONS: Arterial stiffness as defined by an elevated baPWV is associated with an increased prevalence of CAC in a general population-based setting among Japanese men. PMID- 26269006 TI - Copy number variations and gene polymorphisms of complement components in ocular Behcet's disease and Vogt-Koyanagi-Harada syndrome. AB - Complement is involved in many immune-mediated diseases. However, the association of its copy number variations (CNVs) and polymorphisms with Behcet's disease (BD) and Vogt-Koyanagi-Harada syndrome (VKH) is unknown. We examined copy number and mRNA expression by real-time PCR. Cytokine production by stimulated peripheral blood mononuclear cells (PBMCs) in genotyped individuals was measured by ELISA. The frequencies of having more than two copies of C3 were significantly increased in BD and VKH, whereas CNV of C5 was only associated with BD. Increased frequencies of the GG genotype of C3 rs408290 and C5 rs2269067 were found in BD. No association was observed between C3 and C5 SNPs and VKH. mRNA expression in the high CNV group and GG cases of C3 and C5 was significantly higher compared to other genotypes. Increased interleukin-17 and IFN-gamma was observed in the high CNV group and GG genotype cases of C3. Interleukin-17 but not IFN-gamma was increased in the high CNV group and GG genotype cases of C5. No effect of C3 or C5 genetic variants was seen on the production of TNF-alpha, IL-10, IL-1beta, MCP 1, IL-6 and IL-8. Our study thus provides further evidence for a role of complement in the pathogenesis of uveitis. PMID- 26269008 TI - [Pay attention to the prevention of intraoperative complications of total thyroidectomy]. AB - The incidence of thyroid cancer has increased sharply year by year. Thyroid cancer ranked from the 14th in 2003 to the 4th in 2012 most common cancers in female in Beijing. Surgery is still main solution for thyroid cancer, there are two operative procedure for thyroid cancer: total thyroidectomy, lateral lobectomy and isthmus resection. The surgeon must pay attention to intraoperative recurrent laryngeal nerve and parathyroid injury, with particular emphasis on the prevention of total thyroidectomy complications. Precise dissection of thyroid capsule, intraoperative recurrent laryngeal nerve monitoring and application of lymphatic mapping to recognize and protect negative stained parathyroid by using carbon nanoparticles tracer is prone to reduce the incidence of recurrent laryngeal nerve and parathyroid injury in the total thyroidectomy. PMID- 26269007 TI - Occupational contact dermatitis caused by (3-mercaptopropyl)trimethoxysilane in a windscreen repairer. PMID- 26269009 TI - [Minimally invasive parathyroid surgery]. AB - With the advances in techniques of localization, numerous minimally invasive parathyroid surgery were developed including open minimal incision and endoscopic approaches. According to the research results and the experiences from Peking Union Medical College Hospital, the indication and preoperative preparation were discussed in this paper. Some suggestions were given for minimally invasive parathyroid surgery in China. PMID- 26269010 TI - [Three-dimensional total endoscopic thyroidectomy for thyroid carcinoma: a series of 32 cases]. AB - OBJECTIVE: To summarize the experiences of applying three-dimensional (3D) technique in scarless endoscopic thyroidectomy (SET) via anterior chest approach. METHODS: Medical records of patients who undenvent SET using 3D technique from December 2013 to May 2014 were retrospectively reviewed. A total of 32 patients who had a preoperative ultrasound-guided fine-needle aspiration cytology diagnosis of unilateral papillary thyroid carcinoma and underwent lobectomy associated with central lymph node dissection were included in this study. All patients were female with a mean age of (37 +/- 10) years at diagnosis. In addition, 45 female patients who underwent traditional endoscopic thyroidectomy at the same period were randomly selected as control. RESULTS: All surgical procedures were successfully finished. The mean surgical time in 3D group was (91. 7 +/- 11. 4) minutes, and mean hospitalization time was (3. 2 +/- 0. 5) days. Contemporary hoarseness was observed in one patient, and no bleeding, infection, hypocalcemia and other postsurgical complications were observed. Compared to the traditional endoscopic surgery group, 3 D group had significantly shorter surgical time of lobectomy ((23. 2 +/- 5. 1) minutes vs. (28. 0 +/- 5. 0) minutes, t = 4. 156, P = 0. 000). Negative results were seen in the time taking of creating surgical space ((14. 6 +/- 3. 3) minutes vs. (15. 6 +/- 2. 5) minutes), central lymph node dissection ((25. 1 +/- 5. 4) minutes vs. (24. 4 +/- 6. 3) minutes) and total surgical time ((91.7 +/- 11. 4) minutes vs. (96. 1 +/- 13. 0) minutes). CONCLUSION: Application of 3D technique in endoscopic surgery can offer 3D vision of the surgical field, thus significantly shorten lobectomy time and more easily to achieve fine dissection and functional protection of recurrent laryngeal nerves, parathyroids and other vital anatomic structures. PMID- 26269011 TI - [The diagnosis and treatment of late acute rejection after adult orthotopic liver transplantation]. AB - OBJECTIVE: To explore the diagnosis, treatment and long-term outcome of late acute rejection (LAR) following adult orthotropic liver transplantation (OLT). METHODS: A total of 398 consecutive adult patients who underwent OLT in Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University between January 2007 and December 2012 were reviewed retrospectively. There were 48 patients (12. 1%) developed to LAR, including 43 male patients and 5 female patients, with an average age of (52 +/- 13) years(18 - 70 years). The mean body mass index was (22.1 +/- 4. 5) kg/m2 (15. 4 - 30. 4 kg/m2). The indications of the liver transplantation recipients included 16 cases of end-staged liver cirrhosis after hepatitis B or C(33. 3%), 14 cases with severe hepatitis (29. 2%), 9 cases of primary liver cancer(18. 5%), 5 cases of alcoholic liver cirrhosis (10. 4%), 1 case with autoimmune liver disease (2. 1%) , the other 3 cases (6. 3%). They were followed up by outpatient service, telephone and other means. Survival curves were generated with the Kaplan-Meier method and Cox proportional hazards modeling was used for predictors of mortality. Statistically significant variables found by single factor regression analysis were put into the Cox proportional hazards regression model of multivariate analysis. RESULTS: The time-to-event was 23. 6 months after OLT which were more common in the first year to the third year post-transplant (26/48,52. 4%). Thirty-five cases were assessed as mild, 11 cases were assessed as moderate, and 2 cases were assessed as severe ,based on the Banff schema. After adjustment to the immunosuppressive regimen, the overall recovery rate reached to 81. 3%. The rate of steroid resistant acute rejection was 11. 8% (4/34). Inadequate immunosuppression and steroid pulsation were two independent risk factors affecting the prognosis of LAR (P = 0. 008, P = 0. 003, respectively). CONCLUSIONS: LAR is an uncommon complication after OLT. Inadequate immunosuppression and steroid pulsation are the major risk factors for prognosis of LAR. Improving patient compliance and strengthening blood concentration surveillance can increase the patient survival. PMID- 26269012 TI - [The clinical experience and plasmapheresis treatment outcome in treatment of hyperlipidemia acute pancreatitis among Uyghur]. AB - OBJECTIVE: To investigate the clinical features and plasmapheresis treatment outcome of hyperlipidemic acute pancreatitis among Uyghur population. METHODS: The clinical data of 41 cases (treatment group) diagnosed with acute hyperlipidemic pancreatitis and treated with plasmapheresis from August 2007 to August 2012 was studied, and treatment outcomes were statistically analyzed. Fifty patients during the same period who received medical treatment without plasmapheresis (control group) were collected, and were compared to the treatment group. Clinical data of 72 Han Chinese patients with hyperlipidemic acute pancreatitis from the same study period were compared to 91 Uyghur patients mentioned above. The data were analyzed by t-test or chi2 test. RESULTS: Treatment group and control group were comparable in terms of gender, age, APACHE II score at admission, BMI, and blood lipid levels. Thirty-two patients out of 41 in the treatment group were improved after routine medical treatment and plasmapheresis, but 9 died. In the control group, 28 out of 50 cases were improved, 22 died. The mortality of the treatment group was significantly lower than that of the control group(chi2 = 10. 824, P = 0. 001). Time of hospital stay in treatment group was (17 +/- 16) days, and significantly shorter than that of control group ((28 +/- 20) days) (t= 2. 851, P = 0. 005). Before plasmapheresis in the treatment group, serum triglyceride and total cholesterol levels were (58 +/- 39) mmol/L and (24 +/- 8) mmol/L, after plasmapheresis, these values dropped significantly to (10 +/- 10) mmol/L and (6 +/- 5) mmol/L. APACHE II score of those died were 18 +/- 2, and significantly higher than those who survived(11 +/- 3) (t = 0. 570, P = 0. 000); Time from hospital admission until plasmapheresis were significantly longer in died patients ((49 +/- 9) hours) than in survived patients ((38 +/- 8) hours, t = 3. 549, P = 0. 040). Furthermore, serum triglyceride levels were significantly higher in survived cases ((46 +/- 16) mmol/L) than those who died ((37 +/- 15) mmol/L) (t = 2. 386, P = 0. 010) . Both serum triglyceride and cholesterol levels were reduced significantly in control group (t = 3. 484, P = 0. 00; t = 4. 086, P = 0. 000, but the degrees of reduction were significantly lower than that of the treatment group. When comparing Uyghur patients to Han patients, Uyghur cases had higher serum triglyceride (t = 2. 083, P = 0. 039), and cholesterol levels (t = 2. 535, P = 0. 012, and their age was significantly younger than that of Hans (t = 3. 373, P = 0. 010 . CONCLUSIONS: s Uyghur patients with hyperlipidemia acute pancreatitis tend to have higher serum triglyceride and cholesterol levels, and age at disease onset is younger. Plasmapheresis is a more effective treatment option for patients with hyperlipidemia acute pancreatitis. Treatment outcome is related to APACHE II score, serum triglyceride levels, and time frame between admission and plasmapheresis treatment. PMID- 26269013 TI - [Study on the morphology of sagittal of lumbar endplate in healthy adult]. AB - OBJECTIVE: To provide a theoretical basis for designing of lumbar intervertebral disc prosthesis by collecting the data of the lumbar endplate morphology. METHODS: A total of 100 healthy adults were measured about the following parameters: lumbar lordosis, the Cobb angle of each segment, the concavity depth (ECD) of the endplate, the location of concavity apex (ECA) of the endplate. And a correlation analysis on lumbar lordosis and ECD, ECA was made, respectively. RESULTS: In total, 100 volunteers were measured. The mean age of the volunteer was 40 years (range 20 - 50 years); the average depth of ECD was (2. 37 +/- 1. 42) mm, the average location of ECA was (52. 21 +/- 9. 70) %; the average depth of ECD of inferior endplate (IEP) was (2. 81 +/- 1. 52) mm (0. 54 - 7. 60 mm), and the parameter of the superior endplate (SEP) was (1. 94 +/- 1. 16)mm(0. 39 - 6. 10 mm). The average depth of ECD of the IEP was bigger than of the SEP for each lumbar vertebral body. Most of the location of ECA was at the back of the intervertebral body, the average location of ECA of IEP was (49. 60 +/- 8. 78) % (22. 57% - 75. 58%), and the parameter of the SEP was (55. 03 +/- 9. 90) % (16. 03% -75. 58%); the mean angle of lumbar lordosis was 39. 760 11. 25 degrees (13. 8 degrees - 72. 00 degrees ). There was no obvious correlation between the lumbar lordosis and the ECD (r -0. 193, P =0. 195), neither was the location of ECA(r =0. 080, P =0. 592). CONCLUSION: Most of the location of ECA is at the back of the intervertebral body, the average depth of ECD is 2. 37 mm, the average location of ECA is 52. 21%. PMID- 26269014 TI - [Analysis of surgical treatment with pectoralis major muscle flap for deep sternal infection after cardiac surgery: a case series of 189 patients]. AB - OBJECTIVE: To analyze and summarize the clinical features and experience in surgical treatment of deep sternal infection (DSWI). METHODS: This was a retrospective study. From January 2008 to December 2013, 189 patients with secondary DSWI after cardiac surgery underwent the pectoralis major muscle flap transposition in our department. There were 116 male and 73 female patients. The mean age was (54 +/- 21) years, the body mass index was (26. 1 +/- 1. 3) kg/m2. The incidence of postoperation DSWI were after isolated coronary artery bypass grafting (CABG) in 93 patients, after other heart surgery plus CABG in 13 patients, after valve surgery in 47 patients, after thoracic aortic surgery in 16 patients, after congenital heart disease in 18 patients, and after cardiac injury in 2 patients. Clean patients' wound and extract secretions, clear the infection thoroughly by surgery and select antibiotics based on susceptibility results, and then repair the wound with appropriate muscle flap, place drain tube with negative pressure. Of all the 189 patients, 184 used isolate pectoralis, 1 used isolate rectus, and 4 used pectoralis plus rectus. RESULTS: The operative wounds of 179 patients were primary healing (94. 7%). Hospital discharge was postponed by 1 week for 7 patients, due to subcutaneous wound infection. Subcutaneous wound infection occurred again in 8 patients 1 week after hospital discharge, and their wounds healed after wound dressing. Nine patients (4. 7%) did not recover, due to residue of the sequestrum and costal chondritis, whom were later cured by undergoing a second treatment of debridement and pectoralis major muscle flap transposition. Eight patients died, in which 2 died of respiratory failure, 2 died of bacterial endocarditis with septicemia, 2 died of renal failure, 1 died of intraoperative bleeding leading to brain death and the 1 died of heart failure. The mortality rate was 4. 2% . The average length of postoperative hospital stay was (14 +/- 5) days. The longest postoperative follow-up period was 40 months, the median time was 26 months, the follow-up rate was 83. 9% . Totally 179 patients were no-reinfected, 2 patients were reinfected because of artificial vascular rejection. CONCLUSION: To perform surgical debridement and then reconstruct the sternal defect with pectoralis major muscle flap actively for the patient is an effective measure to improve patient's survival rate. PMID- 26269015 TI - [Treatment for giant pituitary adenomas through transcranial approach in a series of 112 consecutive patients]. AB - OBJECTIVE: To investigate the clinical features, surgical transcranial approaches and outcomes of giant pituitary adenomas. METHODS: A series of 112 consecutive cases of giant pituitary adenomas underwent microsurgery through transcranial approaches at People' s Liberation Army General Hospital were retrospectively analyzed. Of the 112 patients, 58 were male and 54 were female, with age ranging from 3 to 72 years(mean age 44. 3 years). There were 91 non-functioning adenomas and 21 hormone-secreting adenomas. The maximum tumor diameter varied from 4. 0 to 7. 2 cm, with mean diameter of 4. 8 cm. Unilateral subfrontal approach was chosen in 16 cases, pterional approach in 41 cases, anterior interhemispheric approach in 34 cases, transcallosal-interforniceal approach in 6 cases, transcortical- transventricular approach in 5 cases, combined approach in 6 cases and other approaches in 4 cases. Postoperative MRI and endocrine function were re-examined routinely to evaluate the therapeutic efficacy. Staged operation through transsphenoidal approach or adjuvant treatments including medical and radiation therapies were administered in patients with hormone-secreting adenomas when hormonal excess persisted after surgery and in patients with non-functioning adenomas who had postoperative MRI evidence of residual tumor. RESULTS: Total removal of the lesion was achieved in 57 cases (50. 9%) , 26 patients (23. 2%) underwent subtotal resection, and 29 patients (25. 9%) underwent partial removal. Postoperative mortality occurred in 3 patients (2. 7%). Major surgical morbidity occurred in 38 patients (33. 9%). Vision was preserved or improved in 98 patients (87. 5%). The postsurgical follow-up period varied from 3 to 64 months (mean 19. 5 months) . Nineteen of the 21 patients with hormone-secreting adenomas were considered to be in hormonal remission, and 87. 2% of the cases were capable of normal work and life and 8 patients suffered recurrence during the followed-up period. CONCLUSIONS: Selection of appropriate transcranial approaches is the key to successful microsurgery for giant pituitary adenomas according to the morphological characteristics presented in image examinations and clinical symptoms. Staged transsphenoidal operation and/or adjuvant therapies including medical and radiation therapies offer the best chances to control the residual tumors after the maximal surgical removal of giant adenomas through transcranial approaches. PMID- 26269016 TI - [The value of taking surgical margin specimens during transurethral resection of bladder tumor in the diagnosis and treatment of non-muscle invasive bladder cancer]. AB - OBJECTIVE: To evaluate the value of taking surgical margin specimens during transurethral resection of bladder tumor(TURBT) in the diagnosis and treatment of non-muscle invasive bladder cancer. METHODS: The data of 356 patients with non muscle invasive bladder cancer from June 2009 to January 2014 were analyzed retrospectively. A standardized protocol were performed during TURBT in 176 patients(surgical margin group), by taking surgical margin specimens from tumor base and 'normal'-appearing margin sites. The other 180 cases merely received general TURBT (general group). To observe the positive rate of surgical margin specimens and whether the diagnosis and treatment plan changed in the surgical margin group. Using Chi-square test to compare the recurrence and progression rates between surgical margin and general groups. To compare their recurrence free survival time by Mann-Whitney U test. Results Of these 176 surgical margin specimens, the positive rate was 19. 3% (34/176),which consists of tumor base 11. 9% (21/176) and tumor normal-appearing margin 7. 4% (13/176). Following with urothelial carcinoma Ta stage in 1. 7% (3/176), T1 stage in 5. 7% (10/176), T2 stage in 8. 0% (14/176), carcinoma in situ (Tis) in 4. 0% (7/176). Among these 176 patients final diagnosis were changed in 10. 8% (19/176) patients due to the specimens results, and 18. 2% (32/176) patients altered their treatment plans. All 356 patients with a mean follow-up of 36. 8 months (6 to 60 months). Two groups of patients(surgical margin group vs. general group) recurrence rates respectively were 22. 2% (39/176) vs. 35. 6% (64/180), recurrence-free survival time were 33. 0 months vs. 23. 5 months and progression rates were 5. 7% (10/176) vs. 10. 6% (19/180). Compared with general group, patients who were taken additional surgical margin specimens showed significantly lower recurrence rate (chi2 = 7. 677, P = 0. 007) and longer recurrence-free survival time (U = 12 605,P = 0. 001). While the progression rate showed no statistical difference between them (chi2 = 2. 825, P = 0. 121). CONCLUSION: Taking additional surgical margin specimens during transurethral resection of bladder tumor is helpful for pathological diagnosis and the planning of further treatment. PMID- 26269017 TI - [The risk of esophageal squamous cell carcinoma associated with microsatellite polymorphism in promoter of heme oxygenase-1]. AB - OBJECTIVE: To investigate the relationship between (GT)n polymorphism and esophageal cancer by analyzing the connection between microsatellite polymorphisms in the promoter of heme oxygenase-1 and the clinicopathological characteristics of esophageal squamous cell carcinoma (ESCC) in Han chinese population. METHODS: The (GT)n repeats in HO-1 gene in 83 male and 43 female hospital-based patients with ESCC (aged between 40 and 79 years with a mean of (61 +/- 8) years) and 134 healthy control individuals were obtained by DNA sequencing. Polymorphisms of the (GT)n repeats were generally grouped into three classes based on allele frequencies: class S alleles (<25 repeats), class M alleles (25 to 29 repeats), and class L alleles (>=30 repeats). The correlation between susceptibility and clinicopathological characteristics of ESCC were analyzed by chi2 test. For in vitro experiments, the transient-transfection assay was performed to explore the correlation between different lengths of (GT)n repeats and promoter activity by assessing the promoter activities of HO-1 gene in cultured Ecal09 cells treated with H2O2 by analysis of cariance. RESULTS: Higher frequencies of L-allele (25. 8% vs. 14. 9%, chi2 = 9. 520, P = 0. 002), L allele carrier (41. 3% vs. 27. 6%, chi2 = 5. 381 , P = 0. 020) were found in patients with ESCC. Furthermore, the lymphatic metastasis rate (63. 5% vs. 41. 8%, chi = 5. 685, P = 0. 017) and the detection rate of poorly differentiated ESCC cell (53. 8% vs. 28. 4%, chi2 = 8. 335, P = 0. 004) was significantly higher in L-allele carriers compared to non-L-allele carriers. In transfection experiments, promoter activities of 5'-flanking regions of the HO-1 gene in Eca109 cells transfected with the recombinant gene carrying (GT)16 repeat after treatment with H2O2 increased (F = 23. 615,P = 0. 008). In H2O treated control group, compared to (GT)26 and (GT)36, the basal promoter activities of HO-1 gene carrying (GT)16 repeat increased (F =41. 376, P = 0. 003; F = 50. 761, P = 0. 002). CONCLUSION: The long (GT)n repeats of HO-1 gene promoter can increase the susceptibility of esophageal squamous cell carcinoma and the risk of lymphatic metastasis. PMID- 26269018 TI - [The biomechanical analysis of craniovertebral junction finite element model in atlas assimilation]. AB - OBJECTIVE: To study the biomechanical change of the craniovertebral junction in conditions of atlas assimilation. METHODS: Mimics software was used to process CT data of the craniovertebral junction in a health adult to obtain the three dimensional reconstruction and the cloudy points of C1, C2 and part of the occipital bone. Then the cloudy points were imported into the Abaqus 6. 8 software to establish the occipito-atlantoaxial finite element model in normal structure. According to the established model in normal structure, the model in conditions of atlas assimilation was set by changing the model parameters. Both models of normal structure and atlas assimilation were loaded with 1. 5 N . m static moment to simulate four motions of flexion, extension, lateral bending and axial rotation respectively. The movement characteristics,joint stress force and ligament deformation was analyzed. RESULTS: Under 1. 5 N . m moment, in model of atlas assimilation the C1-C2 range of movement decreased from 13. 55 degrees to 11.88 degrees in flexion,increased from 13. 22 degrees to 15. 24 degrees in extension and from 4. 05 degrees to 4. 23 degrees in lateral bending and remained unchanged in axial rotation when compared with the normal model. In flexion movement, the contact force of the atlanto-dental joint increased from 1. 59 MPa to 3. 28 MPa and the deflection of apical ligament, tectorial membrane and alar ligament increased 129. 1%, 157. 6% and 75. 1% respectively when compared with the normal model. CONCLUSIONS: The normal C1-C2 motion mode is destructed in conditions of atlas assimilation, leading to the changes of the range of movement,joint stress force and the ligament deformation at C1 C2 junction. The atlantoaxial instability will likely occur in flexion motion. PMID- 26269019 TI - [The role of high mobility group box 1 in the signaling pathways of mouse intestinal ischemia-reperfusion injury]. AB - OBJECTIVE: To investigate the role of high mobility group box 1 (HMGB1) in the signaling pathway of mouse intestinal ischemia-reperfusion injury. METHODS: Twenty-four Specific Pathogen free male C57BL / 6 mice were randomly divided into three groups (n = 8) : the sham operation group (sham), the control group(control) and the HMGB1 antibody group (anti-HMGB1). The vehicle alone or anti-HMGB1 antibody(1 mg/kg, 0. 025%) was injected respectively via the caudal vein 30 min prior to ischemia in the control group or the anti-HMGB1 group. All mice were anesthetized,opened abdominal wall and exposed arteria mesenterica superior. The control group and the anti-HMGBl group underwent 60 min of mesenteric ischemia and 60 min of reperfusion and the sham group were merely opened abdominal wall for 120 min without ischemia-reperfusion. The levels of NF kappaB p65, IL-6 and TNF-alpha in plasma and the activity of MPO in lung and liver and the morphological changes of lung and intestinal tissue were measured. The mRNA levels of HMGB1 and NF-kappaB were evaluated using real-time quantitative PCR and the protein levels of HMGB1 and NF-KB were evaluated using Western blot. The experimental data was analyzed using one-way analysis of variance. RESULTS: The levels of IL-6, TNF-alpha and NF-kappaB p65 in plasma was significantly higher in the control group and the anti-HMGB1 group compared with the sham group (the sham group vs. the control group vs. the anti-HMGB1 group, NF kappaB p65, 104. 64 +/- 11. 89: 228. 53 +/- 24. 85: 145. 00 +/- 33. 63, F = 38. 036, P <0. 05; IL-6,50. 02 +/- 6. 33:104. 91 +/- 31. 18:62. 28 +/- 6. 73, F = 49. 763, P < 0. 05; TNF-alpha, 43. 79 +/- 4. 18: 70. 81 +/- 6. 97: 52. 76 +/- 5. 71, F = 34. 571, P < 0. 05). The increasing degree in the anti- HMGB1 group was significantly reduced compared with the control group (P <0. 05). The activity of MPO of liver and lung in the control group and the anti-HMGB1 group was significantly higher than those in the sham group (P <0. 05). Compared with the sham group, the degree of tissue injury in jejunum, ileum and lung was serious in the control group, and that in the anti-HMGB1 group was significantly lower than the control group. The expression of HMGB1 mRNA and NF-kappaB mRNA in the lung and the ileum in the sham group and the control group were all higher than the sham group (HMGB1 mRNA in lung: sham group 1. 04 +/- 0. 19 vs. control group 2. 25 +/- 0. 18 vs. anti-HMGB1 group 1. 89 0. 18, F = 66. 203, P < 0. 05; in ileum: 1. 14 +/- 0. 54 vs. 6. 26 +/- 0. 60 vs. 4. 93 0. 55, F = 133. 427, P < 0. 05; NF kappaB mRNA in lung: 1. 03 +/- 0. 21 vs. 2. 04 +/- 0. 29 vs. 1. 42 +/- 0. 23, F =26. 229, P < 0. 05; ileum: 1. 03 +/- 0. 23 vs. 3. 71 +/- 0. 53 vs. 2. 23 +/- 0. 55, F = 50. 477, P <0. 05). Subjected to intestinal ischemia-reperfusion injury, the protein expression of HMGB1 and NF-kappaB in the lung, jejunum and ileum in the control group and the anti-HMGB1 group increased compared with the sham group(P <0. 05), but that was significantly lower in the anti-HMGB1 group than the control group (P <0. 05). CONCLUSION: The administration of anti-HMGB1 antibodies may reduce the damage caused by ischemia-reperfusion effectively. PMID- 26269020 TI - [Research progress of the lymph node dissection posterior to fight recurrent laryngeal nerve of papillary thyroid carcinoma]. AB - Central neck lymph node is the main site of metastasis of papillary thyroid cancer. However, the central area of dissection scope and integrity are still issues and controversies. The vast majority of papillary thyroid cancer in central lymph node dissection process, ignoring the lymph node posterior to fight recurrent laryngeal nerve (LN-prRLN), strictly speaking, does not do the central area of lymphatic adipose tissue intact, completely removed. This paper summarizes the recent literature on the LN-prRLN clinical dissection scope, the incidence of LN-prRLN transfer, LN-prRLN dissection impact on the incidence of complications, recurrence rate, mortality and survival rate were reviewed analysis, summarized the LN-prRLN dissection indications, clinical significance and importance. PMID- 26269021 TI - [Recent progress in application of local drug delivery for preventing restenosis after peripheral arterial revascularization]. AB - Restenosis following vascular revascularization remains an important clinical problem. Local drug delivery which can provide enough drug concentration in the lesion location without causing adverse systemic effect is an excellent solution for this question. We conducted a systematic literatory search on PubMed and CKNI through May 2014. After reviewing all related papers, we provided a comprehensive overview of the available drugs and techniques for local drug delivery that have been developed to prevent restenosis after peripheral vascular interventions, including innovations that have been tested only in animals as well as those already approved for clinical use. In brief, anti-proliferative drugs such as paclitaxel and sirolimus are the most used and suitable drugs for local delivery system. Additionally, some promising drugs including anti-inflammatory drugs, antioxidant drugs and drugs inhibiting cell proliferation and migration are already being tested in pre-clinical trials or animal models. At the same time, intraluminal and extraluminal delivery devices have also got a rapid development during the past decades. The efficacy of drug-eluting stent, drug-eluting balloon, porous and microporous balloon and the most recent drug-eluting bioresobable scaffold for preventing of restenosis in peripheral vessels have been demonstrated in humans or in animals, some of them even have received the CE mark in Europe. Endovascular microinfusion catheter and drug-loaded perivascular wraps have only been tested in animal models, more researches are needed. With the development of pharmacology and bioengineering, great strides will be made in the prevention of restenosis in the near future. PMID- 26269023 TI - Development and Evaluation of the New Predictive Models in Tuberculous Pleuritis. AB - Different pleural fluid biomarkers have been found useful in the discrimination between tuberculous pleural effusion (TPE) and non-TPE, with interferon gamma (IFN-gamma) showing the highest single marker diagnostic accuracy. The aim of the present study was to develop predictive models based on clinical data and pleural fluid biomarkers, other than IFN-gamma, which could be applied in differentiating TPE and non-TPE. Two hundred and forty two patients with newly diagnosed pleural effusion were prospectively enrolled. Upon completion of the diagnostic procedures, the underlying disease was identified in 203 patients (117 men and 86 women, median age 65 years; 44 patients with TPE and 159 with non-TPE) who formed the proper study group. Pleural fluid level of ADA, IFN-gamma, IL-2, IL-2sRalpha, IL-12p40, IL-18, IL-23, IP-10, Fas-ligand, MDC, and TNF-alpha was measured and then ROC analysis and multivariate logistic regression were used to construct the predictive models. Two predictive models with very high diagnostic accuracy (AUC > 0.95) were developed. The first model included body temperature, white blood cell count, pleural fluid ADA and IP-10. The second model was based on age, sex, body temperature, white blood cell count, pleural fluid lymphocyte percentage, and IP-10 level. We conclude that two new predictive models based on clinical and laboratory data demonstrate very high diagnostic performance and can be potentially used in clinical practice to differentiate between TPE and non-TPE. PMID- 26269022 TI - Loss of NOX-Derived Superoxide Exacerbates Diabetogenic CD4 T-Cell Effector Responses in Type 1 Diabetes. AB - Reactive oxygen species (ROS) play prominent roles in numerous biological systems. While classically expressed by neutrophils and macrophages, CD4 T cells also express NADPH oxidase (NOX), the superoxide-generating multisubunit enzyme. Our laboratory recently demonstrated that superoxide-deficient nonobese diabetic (NOD.Ncf1(m1J)) mice exhibited a delay in type 1 diabetes (T1D) partially due to blunted IFN-gamma synthesis by CD4 T cells. For further investigation of the roles of superoxide on CD4 T-cell diabetogenicity, the NOD.BDC-2.5.Ncf1(m1J) (BDC 2.5.Ncf1(m1J)) mouse strain was generated, possessing autoreactive CD4 T cells deficient in NOX-derived superoxide. Unlike NOD.Ncf1(m1J), stimulated BDC 2.5.Ncf1(m1J) CD4 T cells and splenocytes displayed elevated synthesis of Th1 cytokines and chemokines. Superoxide-deficient BDC-2.5 mice developed spontaneous T1D, and CD4 T cells were more diabetogenic upon adoptive transfer into NOD.Rag recipients due to a skewing toward impaired Treg suppression. Exogenous superoxide blunted exacerbated Th1 cytokines and proinflammatory chemokines to approximately wild-type levels, concomitant with reduced IL-12Rbeta2 signaling and P-STAT4 (Y693) activation. These results highlight the importance of NOX derived superoxide in curbing autoreactivity due, in part, to control of Treg function and as a redox-dependent checkpoint of effector T-cell responses. Ultimately, our studies reveal the complexities of free radicals in CD4 T-cell responses. PMID- 26269026 TI - Biochemistry of Oxidative Stress. AB - Generation of reactive oxygen species is a physiological process that take place in every aerobic organism. Oxidative stress is defined as a disturbance in the balance between the production of free radicals and antioxidants in favor of the oxidants. The imbalance between those two fractions may potentially lead to cell damage at molecular level. Since oxidants are formed at a different rate as a normal product of aerobic metabolism, complex biochemical mechanisms are required to regulate the entire process. PMID- 26269025 TI - Increased Serum IgA in Children with IgA Nephropathy, Severity of Kidney Biopsy Findings and Long-Term Outcomes. AB - The aim of the study was to determine whether an elevated IgA level at the time of the diagnosis of IgA nephropathy has an effect on the severity of kidney biopsy findings and long-term outcomes in children. We retrospectively studied 89 children with IgA nephropathy who were stratified into Group 1- elevated serum IgA and Group 2 - normal serum IgA at baseline. The level of IgA, proteinuria, hematuria, glomerular filtration rate (GFR) and hypertension (HTN) were compared at baseline and after the end of the follow-up period of 4.0 +/- 3.1 years. Kidney biopsy findings were evaluated using the Oxford classification. The evaluation of treatment included immunosuppressive therapy and renoprotection with angiotensin converting-enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB), or no treatment. The elevated serum IgA was found in 46 (52 %) patients and normal serum IgA level was found in 43 (48 %) patients. No differences were found between the two groups regarding the mean age of patients, proteinuria, and the number of patients with reduced GFR or HTN at baseline. In kidney biopsy, mesangial proliferation and segmental sclerosis were significantly more common in Group 1 compared with Group 2 (p < 0.05). Immunosuppressive therapy was used in 67 % children in Group 1 and 75 % children in Group 2. The Kaplan-Meier survival curves for renal function (with normal GFR) and persistent proteinuria did not differ significantly depending on the serum IgA level at baseline. We conclude that in IgA nephropathy the elevated serum IgA at baseline may be associated with mesangial proliferation and segmental sclerosis contribute to glomerulosclerosis, but has no effect on the presence of proteinuria or on the worsening of kidney function during several years of disease course. PMID- 26269024 TI - Nutrition and Immune System in Children with Simple Obesity. AB - The purpose of this study was to evaluate dietary factors in nutrition influencing the immune system of children and teenagers suffering from simple obesity. The study involved 100 children and teenagers aged 7-18 with simple obesity. Nutritional data were obtained from 3-day food records. The consumed nutrients, including immunomodulators and immunostimulants, were estimated based on the nutrition interview. The results were compared with the nutritional norms. On average, the proportion of n-6:n-3 fatty acids equalled 10:1. Among the amino acids, the highest intake values in the diet were observed for glutamine (13,694.6 mg/day). The study demonstrates inadequate intake levels of iron (73% of recommended dietary allowance, RDA), vitamin C (65% of RDA), and vitamin D (11% of RDA) taking into account the median values for the entire study group. The median daily intake of other nutrients exceeded the RDA values. The diets of the participants in this study were not properly balanced with respect to immunomodulators, which may contribute to the occurrence of immunological disorders and immunodeficiency in this group of patients. PMID- 26269027 TI - The Influence of Primary Cytomegalovirus or Epstein-Barr Virus Infection on the Course of Idiopathic Thrombocytopenic Purpura. AB - Idiopathic thrombocytopenic purpura (ITP) in children is usually triggered by a viral infections such as cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection. The aim of this study was to assess the frequency of CMV and EBV infections in children with first relapse of ITP, and the influence of these infections on the course and response to treatment of ITP. Sixty patients (30 boys and 30 girls) with ITP were enrolled into the study. We found that the age at the onset of ITP was from 1 month to 17 years (mean 7.0 +/- 5.7 years), the platelet number was from 1 to 79 x 10(9)/L (mean 18.1 +/- 19.0 x 10(9)/L) at the time of diagnosis and it increased from 17 to 395 x 10(9)/L (mean 134.4 +/- 81.2 x 10(9)/L)(p < 0.05) after the first course of therapy. Forty seven patients required pharmacological treatment, the duration of the treatment was from 2 to 25 days (mean 6.1 +/- 4.1 days). Relapses were observed in 27 (45%) of the patients. Active CMV infection was found in 19 patients (31.7%), EBV infection in 5 patients (8.3%), and both infections concomitantly in 1 patient (1.7%). The group of patients with CMV or EBV infection(n = 25) did not differ from the patients free of infection (n = 35) in regard to the age, number of platelets at onset, duration of treatment, number of platelets after treatment, number of relapses, and the interval between the onset and first relapse. In conclusion, active CMV or EBV infection is common in children with ITP. These infections do not seem to have an appreciable bearing on the clinical course and the response to treatment on children with ITP. PMID- 26269028 TI - Absence of Typical Symptoms and Comorbidities in Patients with Central Sleep Apnea. AB - Sleep apnea is characterized by pauses in breathing during sleep. There are three forms: central, obstructive, and complex, or mixed sleep apnea. Central sleep apnea, a manifestation of respiratory instability in many clinical conditions and with a variety of causes, is the result of a temporary cessation of breathing in which the inhibitory influences favoring the instability predominate over excitatory influences favoring stable breathing. In contrast to central sleep apnea, according to the published data from previous studies, an association exists between obstructive sleep apnea and various comorbidities, especially chronic obstructive pulmonary disease. This article examines retrospectively the possible association of central sleep apnea with special sleep-related symptoms and various co-morbidities. Data of all patients with different types of central sleep apnea were collected from our hospital charts within the Department of Pneumology, HELIOS Clinic, University of Witten/Herdecke, Wuppertal, Germany, within the study period of January 1, 2011 to September 19, 2014. After clinical examination, all patients underwent polysomnography in our sleep laboratory. We identified a total of 60 (3.5 %) patients with central sleep apnea from 1722 patients with assumed sleep disordered breathing of the mean age of 68.2 +/- 13.7 years (44 males - 73.3 %, 95 % CI 0.6-0.9 and 16 females - 26.7 %, 95 % CI 0.2 0.4). Typical symptoms of sleep-disordered breathing were not observed. A relation to co-morbidities was not found. Central sleep apnea was often diagnosed in the elderly. A direct association between central sleep apnea and symptoms of sleep-disordered breathing and various co-morbidities was not detected. This is in direct contrast to the obstructive sleep apnea syndrome. PMID- 26269029 TI - Prevalence of Olfactory Impairment in Granulomatosis with Polyangiitis. AB - Granulomatosis with Polyangiitis (GPA) is a rare disease of unknown origin. It may damage all organs and systems, even olfactory and taste sense. The aim of the study was to determine the sense of smell in patients with GPA and to identify factors related to disease course, activity, and duration, which may be associated with olfactory dysfunction. The comparison of olfactory function screening scores with Sniffin' Sticks standardized norms showed that 74% of the investigated patients had olfactory dysfunction. The olfactory performance was diminished in all parts of Sniffin' Sticks test: threshold scores 4.4 vs. 7.1 (p = 0.007); odor discrimination 9.0 vs. 11.9 (p = 0.008); and olfactory identification 9.8 vs. 12.2 (p = 0.011) in the GPA patients vs. control subjects, respectively. Scores acquired during all three parts of the test were combined to assess the TDI-score. The median TDI-score in the GPA group (27.5) was significantly lower than that in the control group (32.0) (p = 0.002). Active nasal and paranasal sinus inflammation in GPA leads to olfactory dysfunction, the patients are often unaware of. The dysfunction is permanent and does not abates along with decreasing intensity of the inflammatory process. GPA therapy should include recommendations on nutrition, personal hygiene, and food poisoning prevention. PMID- 26269031 TI - Surgery for high-grade unruptured brain arteriovenous malformations: era for a new paradox? PMID- 26269030 TI - Epidemiology of traumatic brain injury in Europe. AB - BACKGROUND: Traumatic brain injury (TBI) is a critical public health and socio economic problem throughout the world, making epidemiological monitoring of incidence, prevalence and outcome of TBI necessary. We aimed to describe the epidemiology of traumatic brain injury in Europe and to evaluate the methodology of incidence studies. METHOD: We performed a systematic review and meta-analyses of articles describing the epidemiology of TBI in European countries. A search was conducted in the PubMed electronic database using the terms: epidemiology, incidence, brain injur*, head injur* and Europe. Only articles published in English and reporting on data collected in Europe between 1990 and 2014 were included. RESULTS: In total, 28 epidemiological studies on TBI from 16 European countries were identified in the literature. A great variation was found in case definitions and case ascertainment between studies. Falls and road traffic accidents (RTA) were the two most frequent causes of TBI, with falls being reported more frequently than RTA. In most of the studies a peak TBI incidence was seen in the oldest age groups. In the meta-analysis, an overall incidence rate of 262 per 100,000 for admitted TBI was derived. CONCLUSIONS: Interpretation of published epidemiologic studies is confounded by differences in inclusion criteria and case ascertainment. Nevertheless, changes in epidemiological patterns are found: falls are now the most common cause of TBI, most notably in elderly patients. Improvement of the quality of standardised data collection for TBI is mandatory for reliable monitoring of epidemiological trends and to inform appropriate targeting of prevention campaigns. PMID- 26269032 TI - Prior knowledge of the clinical picture does not introduce bias in the histopathologic diagnosis of melanocytic skin lesions. AB - A common debate among dermatopathologists is that prior knowledge of the clinical picture of melanocytic skin neoplasms may introduce a potential bias in the histopathologic examination. Histologic slides from 99 melanocytic skin neoplasms were circulated among 10 clinical dermatologists, all of them formally trained and board-certified dermatopathologists: 5 dermatopathologists had clinical images available after a 'blind' examination (Group 1); the other 5 had clinical images available before microscopic examination (Group 2). Data from the two groups were compared regarding 'consensus' (a diagnosis in agreement by >=4 dermatopathologists/group), chance-corrected interobserver agreement (Fleiss' k) and level of diagnostic confidence (LDC: a 1-5 arbitrary scale indicating 'increasing reliability' of any given diagnosis). Compared with Group 1 dermatopathologists, Group 2 achieved a lower number of consensus (84 vs. 90) but a higher k value (0.74 vs. 0.69) and a greater mean LDC value (4.57 vs. 4.32). The same consensus was achieved by the two groups in 81/99 cases. Spitzoid neoplasms were most frequently controversial for both groups. The histopathologic interpretation of melanocytic neoplasms seems to be not biased by the knowledge of the clinical picture before histopathologic examination. PMID- 26269034 TI - Improve oxidation resistance at high temperature by nanocrystalline surface layer. AB - An interesting change of scale sequence occurred during oxidation of nanocrystalline surface layer by means of a surface mechanical attrition treatment. The three-layer oxide structure from the surface towards the matrix is Fe3O4, spinel FeCr2O4 and corundum (Fe,Cr)2O3, which is different from the typical two-layer scale consisted of an Fe3O4 outer layer and an FeCr2O4 inner layer in conventional P91 steel. The diffusivity of Cr, Fe and O is enhanced concurrently in the nanocrystalline surface layer, which causes the fast oxidation in the initial oxidation stage. The formation of (Fe,Cr)2O3 inner layer would inhabit fast diffusion of alloy elements in the nanocrystalline surface layer of P91 steel in the later oxidation stage, and it causes a decrease in the parabolic oxidation rate compared with conventional specimens. This study provides a novel approach to improve the oxidation resistance of heat resistant steel without changing its Cr content. PMID- 26269033 TI - Involved-field radiotherapy (IFRT) versus elective nodal irradiation (ENI) in combination with concurrent chemotherapy for 239 esophageal cancers: a single institutional retrospective study. AB - BACKGROUND: This retrospective study on early and locally advanced esophageal cancer was conducted to evaluate locoregional failure and its impact on survival by comparing involved field radiotherapy (IFRT) with elective nodal irradiation (ENI) in combination with concurrent chemotherapy. METHODS: We assessed all patients with esophageal cancer of stages I-IV treated with definitive radiotherapy from June 2000 to March 2014. Between 2000 and 2011, ENI was used for all cases excluding high age cases. After Feb 2011, a prospective study about IFRT was started, and therefore IFRT was used since then for all cases. Concurrent chemotherapy regimen was nedaplatin (80 mg/m(2) at D1 and D29) and 5 fluorouracil (800 mg/m(2) at D1-4 and D29-32). RESULTS: Of the 239 consecutive patients assessed (120 ENI vs. 119 IFRT), 59 patients (24.7%) had stage IV disease and all patients received at least one cycle of chemotherapy. The median follow-up time for survivors was 34.0 months. There were differences in 3-year local control (44.8% vs. 55.5%, p = 0.039), distant control (53.8% vs. 69.9%, p = 0.021) and overall survival (34.8% vs. 51.6%, p = 0.087) rates between ENI vs. IFRT, respectively. Patients treated with IFRT (8 %) demonstrated a significantly lower risk (p = 0.047) of high grade late toxicities than with ENI (16%). IFRT did not increase the risk of initially uninvolved or isolated nodal failures (27.5% in ENI and 13.4% in IFRT). CONCLUSIONS: Nodal failure rates in clinically uninvolved nodal stations were not increased with IFRT when compared to ENI. IFRT also resulted in significantly decreased esophageal toxicity, suggesting that IFRT may allow for integration of concurrent systemic chemotherapy in a greater proportion of patients. Both tendencies of improved loco-regional progression free survival and a significant increased overall survival rate favored the IFRT arm over the ENI arm in this study. PMID- 26269035 TI - Ultrathin nanosheets constructed CoMoO4 porous flowers with high activity for electrocatalytic oxygen evolution. AB - Hierarchical CoMoO4 porous micro-flowers assembled from numerous ultrathin nanosheets were synthesized by a facile hydrothermal method. Benefiting from the high specific surface area and constituent nanosheets with an ultrathin thickness, the CoMoO4 micro-flowers exhibit substantially higher electrocatalytic activity and stability than the IrO2 benchmark for the oxygen evolution reaction. PMID- 26269036 TI - To listen, look and think. PMID- 26269037 TI - [A mentor for the medical student]. PMID- 26269038 TI - [The future of primary health care--without research?]. PMID- 26269039 TI - [Re: How doctors do not wish to die]. PMID- 26269041 TI - [Re: How doctors do not wish to die]. PMID- 26269042 TI - [Re: Patient reporting of adverse drug reactions in Norway 2010-13]. PMID- 26269043 TI - [O. Spigset and colleagues reply]. PMID- 26269044 TI - [Re: Different guidelines for treatment of prostate cancer]. PMID- 26269045 TI - [Re: E-cigarettes--harmful or beneficial?]. PMID- 26269046 TI - [Re: E-cigarettes--harmful or beneficial?]. PMID- 26269047 TI - [Re: E-cigarettes--harmful or beneficial?]. PMID- 26269048 TI - [Re: E-cigarettes--harmful or beneficial?]. PMID- 26269049 TI - [T. K. Grimsrud & T. Sanner reply]. PMID- 26269050 TI - [Re: Good employment conditions in hospitals is good for everyone]. PMID- 26269051 TI - [Re: Good employment conditions in hospitals is good for everyone]. PMID- 26269052 TI - [Re: Good employment conditions in hospitals is good for everyone]. PMID- 26269053 TI - [K. Hamandsen & M.H. Christiansen reply]. PMID- 26269057 TI - [The emergency department needs their own specialists]. PMID- 26269058 TI - [Holistic medical education--a shared responsibility]. PMID- 26269059 TI - [Who should become a physician?]. PMID- 26269060 TI - [Putting the patient at the center--already as a student]. PMID- 26269061 TI - [Physical activity without exercising?]. PMID- 26269062 TI - [Alcohol consumption--a natural part of the medical history taking]. PMID- 26269063 TI - [Physicians must contribute in undergraduate medical education]. PMID- 26269066 TI - Assessing alcohol use and smoking among patients admitted to the medical ward. AB - BACKGROUND: The objective of the study was to investigate the incidence of risky alcohol consumption in patients admitted to medical wards, and to examine possible differences in how smoking habits and alcohol consumption are assessed and monitored by health personnel. MATERIAL AND METHOD: The study was conducted on medical wards at Southern Norway Hospital Trust in autumn 2013. Out of 998 patients who were successively admitted, 536 were included in the analysis. A questionnaire was used to survey smoking and risky alcohol consumption, and to determine whether patients could remember being asked and advised about these during their hospitalisation period. RESULTS: Fifty patients (9.3%) fulfilled the criteria for risky alcohol consumption. A lower percentage reported having been asked about their drinking habits than about their smoking habits (44% versus 62%, p < 0.001). Compared to those who smoked, a lower percentage of those with risky alcohol consumption reported that they had been recommended to reduce their consumption or quit; 10% vs. 29% (p = 0.009). INTERPRETATION: The patients' experience was that they were asked less about their alcohol consumption than about smoking. They also reported receiving less health-promoting advice in relation to alcohol. Doctors should be more conscious of including alcohol consumption when taking regular case histories. PMID- 26269067 TI - [First generalized tonic-clonic seizure]. AB - BACKGROUND: First onset of a generalized tonic-clonic seizure is a frequent reason for hospital admissions. This article aims to provide a brief overview of the epidemiology, etiology, investigation and treatment of a first generalized tonic-clonic seizure. MATERIAL AND METHOD: The review is based on a discretionary sample of English-language articles found through a search in PubMed, and the authors' own clinical experience. RESULTS: A first generalized tonic-clonic seizure is traditionally divided into either a provoked or an unprovoked seizure. Provoked seizures occur in close temporal relationship to a systemic disorder or to a brain insult, for example a stroke or a head trauma. Unprovoked seizures occur in the absence of such factors. The incidence of provoked and unprovoked seizures is 35/100.000 person years and 50/100,000 person years, respectively. The occurrence is influenced by genetic and lifestyle factors. The hospital assessment includes a thorough case history, a somatic and neurological examination, ECG, standard EEG, and cerebral MRI. An immediate cerebral CT is often carried out. In case of provoked seizures, both treatment and estimation of the recurrence risk depends on the underlying cause. Antiepileptic drug treatment initiated after a first unprovoked seizure may reduce the risk of seizure recurrence. However, no long term risk reduction has been shown compared to delaying treatment until after a second seizure. INTERPRETATION: Patients who experience a first generalized tonic-clonic seizure are a heterogenous group, and a thorough diagnostic assessment is necessary in order to provide tailored treatment and a reliable prognosis. PMID- 26269068 TI - Black macules on the sole of the foot. PMID- 26269069 TI - [A man in his 70s with hypertension and acute chest pain]. PMID- 26269070 TI - [A baker with asthma]. PMID- 26269071 TI - [Several PhD projects in the health enterprises]. PMID- 26269072 TI - [Building specialist training in Ethiopia]. PMID- 26269073 TI - [July 22--my story]. PMID- 26269074 TI - [Athletic language confusion]. PMID- 26269086 TI - Synthesis and biological evaluation of thiophosphate tricyclic coumarin derivatives as steroid sulfatase inhibitors. AB - Steroid sulfatase (STS) enzyme inhibition is an important approach to the management of hormone-dependent breast cancer. In this paper, we report convenient methods for the synthesis and biological evaluation of thiophosphate tricyclic coumarin analogs exhibiting STS activity. The described methods are based on the straightforward preparation of 7-hydroxy-2,3-dihydro-1H cyclopenta[c]chromen-2-one, 3-hydroxy-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6 one, and 3-hydroxy-8,9,10,11-tetrahydro-7H-cyclohepta[c]chromen-6-one and their further modification by the introduction of various thiophosphate moieties. The inhibition properties of the synthesized compounds were tested toward STS isolated from human placenta. Most of the new STS inhibitors possessed good to moderate activity toward STS. During the course of our investigation, the largest inhibitory effects in the STS enzyme assays were observed for the two compounds 3f and 4r, with IC50 values of 13.3 and 30.3 MUM, respectively (the IC50 value of 1 MUM for the 665-COUMATE was used as a reference). The structure-activity relationships of the synthesized coumarin derivatives toward STS enzymes are discussed. PMID- 26269087 TI - Use of genotype-environment interactions to elucidate the pattern of maize root plasticity to nitrogen deficiency. AB - Maize (Zea mays L.) root morphology exhibits a high degree of phenotypic plasticity to nitrogen (N) deficiency, but the underlying genetic architecture remains to be investigated. Using an advanced BC4 F3 population, we investigated the root growth plasticity under two contrasted N levels and identified the quantitative trait loci (QTLs) with QTL-environment (Q * E) interaction effects. Principal components analysis (PCA) on changes of root traits to N deficiency (DeltaLN-HN) showed that root length and biomass contributed for 45.8% in the same magnitude and direction on the first PC, while root traits scattered highly on PC2 and PC3. Hierarchical cluster analysis on traits for DeltaLN-HN further assigned the BC4 F3 lines into six groups, in which the special phenotypic responses to N deficiency was presented. These results revealed the complicated root plasticity of maize in response to N deficiency that can be caused by genotype-environment (G * E) interactions. Furthermore, QTL mapping using a multi environment analysis identified 35 QTLs for root traits. Nine of these QTLs exhibited significant Q * E interaction effects. Taken together, our findings contribute to understanding the phenotypic and genotypic pattern of root plasticity to N deficiency, which will be useful for developing maize tolerance cultivars to N deficiency. PMID- 26269088 TI - Synthesis of bicyclic tetrahydrofurans from linear precursors using manganese(III) acetate. AB - We have recently developed methodology based on oxidative radical reactions for the synthesis of [3.3.0]-bicyclic lactones containing both cyclopentanes and gamma-lactams along with application of this methodology to the synthesis of natural products and complex molecular architectures. Herein we report an extension of this methodology to the synthesis of oxygen heterocycles including bicyclic bis-lactones. PMID- 26269089 TI - Concentrated growth factor in the treatment of adjacent multiple gingival recessions: a split-mouth randomized clinical trial. AB - AIM: The aim of this study was to determine the clinical effect of concentrated growth factor (CGF) in combination with coronally advanced flap (CAF) compared to CAF alone for the treatment of multiple adjacent gingival recessions (GRs). MATERIALS AND METHODS: Twenty patients with a total of 119 Miller Class I and II GRs in the maxilla were included to this study. Recessions were randomly treated according to a split-mouth design by means of CAF + CGF (test; 60 defects) or CAF (control; 59 defects). Clinical outcomes were evaluated at baseline and 6 months after surgery. RESULTS: The mean root coverage (MRC) was 82.06% and 86.67%, complete root coverage (CRC) was 45.8% (27/59) and 56.7% (34/60) for CAF and CAF + CGF, respectively at 6th month. Statistically no difference was demonstrated between the two groups in terms of recession depth (RD), MRC and CRC at 6th month. The increase in width of keratinized gingiva (KGW) and gingival thickness (GT) were statistically significant in the CAF + CGF group compared to the CAF group at 6th month. CONCLUSIONS: The use of CGF in combination with CAF did not provide additional benefits in RD, CRC and MRC. This study suggests that use of CGF + CAF may increase the success of GRs because of a significant increase in KGW and GT. PMID- 26269090 TI - Circularly Polarized Luminescence in Chiral Molecules and Supramolecular Assemblies. AB - Circularly polarized luminescence, or CPL, is a luminescence phenomenon that provides the differential emission intensity of right and left circularly polarized light, thereby providing information on the excited state properties of the chiral molecular systems. In recent years, there has been a growing interest toward the development of organic chromophores capable of circularly polarized emission due to their potential applications in sensors, asymmetric synthesis as well as display and optical storage devices. The major drawback with organic molecules is the low dissymmetric factors exhibited by these systems. One of the recent strategies adopted for the improvement in luminescence dissymmetry of organic systems is through the controlled self-assembly of chromophores. In this Perspective, we highlight the recent experimental and theoretical developments in the field of chiral organic chromophoric systems and their self-assembly, that has produced promising results toward the enhancement of glum values in CPL. PMID- 26269091 TI - Differential isoform expression and selective muscle involvement in muscular dystrophies. AB - Despite the expression of the mutated gene in all muscles, selective muscles are involved in genetic muscular dystrophies. Different muscular dystrophies show characteristic patterns of fatty degenerative changes by muscle imaging, even to the extent that the patterns have been used for diagnostic purposes. However, the underlying molecular mechanisms explaining the selective involvement of muscles are not known. To test the hypothesis that different muscles may express variable amounts of different isoforms of muscle genes, we applied a custom-designed exon microarray containing probes for 57 muscle-specific genes to assay the transcriptional profiles in sets of human adult lower limb skeletal muscles. Quantitative real-time PCR and whole transcriptome sequencing were used to further analyze the results. Our results demonstrate significant variations in isoform and gene expression levels in anatomically different muscles. Comparison of the known patterns of selective involvement of certain muscles in two autosomal dominant titinopathies and one autosomal dominant myosinopathy, with the isoform and gene expression results, shows a correlation between the specific muscles involved and significant differences in the level of expression of the affected gene and exons in these same muscles compared with some other selected muscles. Our results suggest that differential expression levels of muscle genes and isoforms are one determinant in the selectivity of muscle involvement in muscular dystrophies. PMID- 26269092 TI - Paeoniflorin ameliorates ANIT-induced cholestasis by activating Nrf2 through an PI3K/Akt-dependent pathway in rats. AB - Cholestasis causes hepatic accumulation of bile acids leading to liver injury, fibrosis and liver failure. Paeoniflorin, the major active compound isolated from the roots of Paeonia lactiflora pall and Paeonia veitchii Lynch, is extensively used for liver diseases treatment in China. However, the mechanism of paeoniflorin's hepatoprotective effect on cholestasis has not been investigated yet. In this study, we administered paeoniflorin to rats for 3 days prior to alpha-naphthylisothiocyanate (ANIT) administration for once, then went on administering paeoniflorin to rats for 3 days. The data demonstrated that paeoniflorin significantly prevented ANIT-induced change in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphates (ALP), serum total bilirubin (TBIL), direct bilirubin (DBIL), total bile acid (TBA) and gamma-glutamyl transpeptidase (gamma-GT). Histology examination revealed that paeoniflorin treatment rats relieved more liver injury and bile duct proliferation than ANIT-administered rats. Moreover, our data indicated that paeoniflorin could restore glutathione (GSH) and its related synthase glutamate cysteine ligase catalytic subunit (GCLc) and glutamate-cysteine ligase modifier subunit (GCLm) in ANIT-treated group. In addition, the RNA and protein expression of Akt and nuclear factor-E2-related factor-2 (Nrf2) were also activated by paeoniflorin in ANIT-induced rats. These findings indicated that paeoniflorin protected ANIT-induced cholestasis and increased GSH synthesis by activating Nrf2 through PI3K/Akt-dependent pathway. Therefore, paeoniflorin might be a potential therapeutic agent for cholestasis. PMID- 26269093 TI - Use of model organism and disease databases to support matchmaking for human disease gene discovery. AB - The Matchmaker Exchange application programming interface (API) allows searching a patient's genotypic or phenotypic profiles across clinical sites, for the purposes of cohort discovery and variant disease causal validation. This API can be used not only to search for matching patients, but also to match against public disease and model organism data. This public disease data enable matching known diseases and variant-phenotype associations using phenotype semantic similarity algorithms developed by the Monarch Initiative. The model data can provide additional evidence to aid diagnosis, suggest relevant models for disease mechanism and treatment exploration, and identify collaborators across the translational divide. The Monarch Initiative provides an implementation of this API for searching multiple integrated sources of data that contextualize the knowledge about any given patient or patient family into the greater biomedical knowledge landscape. While this corpus of data can aid diagnosis, it is also the beginning of research to improve understanding of rare human diseases. PMID- 26269094 TI - Effect of isoniazid preventive therapy on tuberculosis or death in persons with HIV: a retrospective cohort study. AB - BACKGROUND: Isoniazid preventive therapy (IPT) is a recommended strategy for prevention of tuberculosis (TB) in persons with Human Immunodeficiency Virus (HIV) although the benefits have not been unequivocally demonstrated in routine clinical practice with widespread ART adoption. Therefore, we assessed the effectiveness of IPT in prevention of TB or death in patients treated with antiretroviral therapy (ART) in a chronic care setting. METHODS: Retrospective cohort study of HIV patients enrolled in chronic care from 2007 to 2013. Eligible participants were HIV infected subjects (age > 15 years) with no (history of) TB. The combined effect of IPT and ART on the composite outcome (TB or death) was estimated using time-dependent Cox regression with adjustment for baseline covariates. RESULTS: 1,922 patients were included, 374 (19.4 %) received IPT and 258 (13.4 %) developed TB or deceased. The median follow-up duration of the cohort was 839 days, with a total of 5491 person years. In unadjusted analysis, the combination of IPT and ART lowered the hazard of TB or death by 65 % [HR = 0.35; 95 % CI (0.16, 0.77)] compared to ART alone. Even after adjustment for confounders, the combined effect of ART and IPT resulted in a 60 % hazard reduction of TB or death in comparison to participants who received ART without IPT [HR = 0.40; 95 % CI (0.18, 0.87)]. The IPT-specific benefit in patients not receiving ART could not be reliably estimated due to high rates of ART adoption. CONCLUSION: The combined effect of IPT and ART to prevent TB or death in HIV patients in a non-experimental setting in comparison to ART alone was estimated to be 60 %. PMID- 26269095 TI - Psychotropic Treatment Pattern in Medicaid Pediatric Patients With Concomitant ADHD and ODD/CD. AB - OBJECTIVE: To describe psychotropic treatment pattern and evaluate the association of socio-demographic factors and psychotropic combination therapy in children with ADHD and oppositional defiant disorder/conduct disorder (ODD/CD). METHOD: This is a cross-sectional drug utilization study based on Medicaid fee for-service programs in 26 U.S. states (1999-2006). Children aged 4 to 18 with concomitant ADHD and ODD/CD were included. We calculated the prevalence of psychotropic drugs and used logistic regression to evaluate the role of socio demographic factors in psychotropic combination therapy. RESULTS: We identified 121,740 children with ADHD and ODD/CD (140,777 person-years). The period prevalence of "no psychotropic therapy," psychotropic monotherapy, and psychotropic dual therapy was 38.1%, 44.7%, and 9.0%, respectively. The most common drug class was stimulants. Whites, males, and children in foster care were more likely to use psychotropic combination therapy. State-level variation was observed. CONCLUSION: "No psychotropic therapy" and stimulants dominate treatment choices in children with ADHD and ODD/CD. Socio-demographic characteristics are associated with combination psychotropic therapy. PMID- 26269096 TI - Psychiatric Comorbidity in Treatment-Seeking Alcohol Dependence Patients With and Without ADHD. AB - OBJECTIVE: To estimate the prevalence of ADHD in adult patients treated for alcohol dependence and to analyze the characteristics of consumption and psychiatric comorbidity, in function of a possible ADHD in adulthood. METHOD: We administered the Adult ADHD Self-Report Scale (ASRS) to 726 alcohol-dependent patients. Clinical diagnosis, following Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR) criteria was made in the first four weeks of treatment. A subsample of 297 patients was evaluated using Conners' Adult ADHD Diagnostic Interview for DSM-IV (CAADID-II) to test the psychometric properties of ASRS. RESULTS: After analyzing the properties of the ASRS (sensitivity: 83.3%; specificity: 66.1%), the prevalence of ADHD, in the whole sample, was estimated to be 16.2%. Being younger, lifetime history of cocaine dependence and the presence of an affective, anxiety or personality disorder were associated with a possible ADHD. CONCLUSION: The estimated prevalence of ADHD in patients being treated for alcohol dependence is high, and the presence of a possible ADHD in adulthood is associated with an increase in psychiatric comorbidity. PMID- 26269097 TI - Acute Kidney Injury With Tobramycin-Impregnated Bone Cement Spacers in Prosthetic Joint Infections. AB - BACKGROUND: Antibiotic-impregnated bone cement spacer (ACS) with tobramycin +/- vancomycin is commonly used in a 2-stage replacement of infected prosthetic joints. This procedure has been associated with development of acute kidney injury (AKI). OBJECTIVE: To determine the incidence and risk factors for AKI after implantation of tobramycin-impregnated ACS. METHODS: This prospective, observational study evaluated 50 consecutive patients who received tobramycin ACS for first-stage revision of an infected hip or knee arthroplasty from August 2011 to February 2013. AKI was defined as 50% or greater rise in serum creatinine (SCr) from baseline within the first 7 postoperative days (PODs). RESULTS: The incidence of AKI was 20%, with median onset occurring at POD 2 (interquartile range [IQR] = 1-3); patients with AKI had a longer median duration of hospital stay (16 days, IQR = 12-17, vs 10 days, IQR = 8-10; P = 0.03). Serum tobramycin concentrations were significantly higher in the AKI group, peaking on POD 1 (median 1.9 vs 0.9 ug/mL, P = 0.01). Risk factors for nephrotoxicity identified by multivariate analysis were use of bone cement premanufactured with gentamicin (OR = 8.2; 95% CI = 1.1-60; P = 0.04), administration of blood transfusions intraoperatively (OR = 32.5; 95% CI = 2.3-454.3; P = 0.01) and nonsteroidal anti inflammatory drugs postoperatively (OR = 23.0; 95% CI = 1.3-397.7; P = 0.03). CONCLUSIONS: Tobramycin ACS is associated with a high risk of AKI. Measures to minimize AKI risk in the perioperative period include early detection through close monitoring of SCr, avoiding use of premanufactured bone cement containing gentamicin, and avoiding potential nephrotoxins within the first 72 hours postoperatively. PMID- 26269098 TI - The effects of an Audio Visual Assisted Therapy Aid for Refractory auditory hallucinations (AVATAR therapy): study protocol for a randomised controlled trial. AB - BACKGROUND: Psychological interventions which adopt an explicitly interpersonal approach are a recent development in the treatment of distressing voices. AVATAR therapy is one such approach which creates a direct dialogue between a voice hearer and a computerised representation of their persecutory voice (the avatar) through which the person may be supported to gain a sense of greater power and control. The main objective of the trial is to test the clinical efficacy of this therapy to reduce the frequency and severity of auditory verbal hallucinations (AVH). Secondary objectives of the study are to explore explanatory mechanisms of action and potential moderators, to carry out a qualitative evaluation of participants' experience and to conduct an economic evaluation. METHODS/DESIGN: The AVATAR randomised clinical trial will independently randomise 142 participants to receive either 7 sessions of AVATAR therapy or supportive counselling (SC). The study population will be individuals with schizophrenia spectrum and other psychotic disorders who report hearing persistent distressing voices, for more than 12 months, which are unresponsive or only partially responsive to antipsychotic medication. The main hypotheses are that, compared to SC, AVATAR therapy will reduce the frequency and severity of AVH and will also reduce the reported omnipotence and malevolence of these voices. Assessments will occur at 0 weeks (baseline), 12 weeks (post-intervention) and 24 weeks (follow up), and will be carried out by blinded assessors. Both interventions will be delivered in a community-based mental health centre. Therapy competence and adherence will be monitored in both groups. Statistical analysis will follow the intention-to-treat principle and data will be analysed using a mixed (random) effects model at each post treatment time point separately. A formal mediation and moderator analysis using contemporary causal inference methods will be conducted as a secondary analysis. The trial is funded by the Welcome Trust (WT). DISCUSSION: AVATAR therapy showed promising effects in a pilot study, but the efficacy of the approach needs to be examined in a larger randomised clinical trial before wider dissemination and implementation in mental health services. TRIAL REGISTRATION: Current Controlled Trials ISRCTN: 65314790 , registration date: 27 March 2013. PMID- 26269099 TI - Primorskyibacter insulae sp. nov., isolated from the junction between the ocean and a freshwater spring. AB - A Gram-stain-negative, aerobic, non-spore-forming, non-flagellated and rod-shaped bacterial strain, designated SSK3-2T, was isolated from the locality where the ocean and a freshwater spring meet at Jeju island, South Korea, and subjected to a polyphasic taxonomic study. Strain SSK3-2T grew optimally at 30 degrees C, at pH 7.0-8.0 and in the presence of 2.0 % (w/v) NaCl. Neighbour-joining, maximum likelihood and maximum-parsimony phylogenetic trees based on 16S rRNA gene sequences revealed that strain SSK3-2T clustered with the type strain of Primorskyibacter sedentarius, with which it exhibited 97.3 % sequence similarity. Strain SSK3-2T contained Q-10 as the predominant ubiquinone and C18 : 1omega7c as the major fatty acid. The major polar lipids detected in strain SSK3-2T were phosphatidylcholine, phosphatidylglycerol, one unidentified lipid and one unidentified aminolipid. The DNA G+C content of strain SSK3-2T was 60.6 mol% and its mean DNA-DNA relatedness value with P. sedentarius JCM 16874T was 19 %. Differential phenotypic properties, together with phylogenetic and genetic distinctiveness, revealed that strain SSK3-2T is separated from P. sedentarius. On the basis of the data presented, strain SSK3-2T is considered to represent a novel species of the genus Primorskyibacter, for which the name Primorskyibacter insulae sp. nov. is proposed. The type strain is SSK3-2T ( = KCTC 42602T = CECT 8871T). PMID- 26269102 TI - Lessons Learned from Asymptomatic Acute Coronary Occlusion Complicating Radiofrequency Ablation of Right Ventricular Outflow Tract Tachycardia. AB - INTRODUCTION: Radiofrequency ablation has become a standard procedure in the treatment of ventricular arrhythmias. The success rate varies according to the etiology and the presence or absence of underlying structural heart disease, while complication rates are relatively low. METHODS: To describe the damage in neighboring structures during the ablation in certain locations. RESULTS: We present a patient who underwent a radiofrequency ablation of sustained monomorphic ventricular tachycadia at the inferior and anterior part of the right ventricular outflow tract, at the insertion of the right ventricle to the left ventricle. Extensive ablation resulted in an asymptomatic occlusion of the mid segment of the left descending coronary artery. CONCLUSION: Creation of deeper and broader lesions with current catheter technologies can result in damage of the adjacent endo- and epicardial structures. Careful evaluation of the area of interest prior to and after the ablation should therefore be mandatory. PMID- 26269101 TI - Old/New Effect of Digital Memory Retrieval in Chinese Dyscalculia. AB - This study reports the neurophysiological and behavioral correlates of digital memory retrieval features in Chinese individuals with and without dyscalculia. A total of 18 children with dyscalculia (ages 11.5-13.5) and 18 controls were tested, and their event-related potentials were digitally recorded simultaneously with behavior measurement. Behavioral data showed that the dyscalculia group had lower hit rates and higher false rates than the control group. The electroencephalography results showed that both groups had a significant old/new effect and that this effect was greater in the control group. In the 300 to 400 ms processing stages, both groups showed significant differences in digital memory retrieval in the frontal regions. In the 400 to 500 and 500 to 600 ms epochs, the old/new effect in the control group was significantly greater than it was in the dyscalculia group at the frontal, central, and parietal regions. In the 600 to 700 ms processing stages, both groups showed significant differences in digital memory retrieval in the frontal, central, parietal, and occipital regions. These results suggest that individuals with dyscalculia exhibit impaired digital memory retrieval. Extraction failure may be an important cause of calculation difficulties. PMID- 26269100 TI - Robust sequence alignment using evolutionary rates coupled with an amino acid substitution matrix. AB - BACKGROUND: Selective pressures at the DNA level shape genes into profiles consisting of patterns of rapidly evolving sites and sites withstanding change. These profiles remain detectable even when protein sequences become extensively diverged. A common task in molecular biology is to infer functional, structural or evolutionary relationships by querying a database using an algorithm. However, problems arise when sequence similarity is low. This study presents an algorithm that uses the evolutionary rate at codon sites, the dN/dS (omega) parameter, coupled to a substitution matrix as an alignment metric for detecting distantly related proteins. The algorithm, called BLOSUM-FIRE couples a newer and improved version of the original FIRE (Functional Inference using Rates of Evolution) algorithm with an amino acid substitution matrix in a dynamic scoring function. The enigmatic hepatitis B virus X protein was used as a test case for BLOSUM-FIRE and its associated database EvoDB. RESULTS: The evolutionary rate based approach was coupled with a conventional BLOSUM substitution matrix. The two approaches are combined in a dynamic scoring function, which uses the selective pressure to score aligned residues. The dynamic scoring function is based on a coupled additive approach that scores aligned sites based on the level of conservation inferred from the omega values. Evaluation of the accuracy of this new implementation, BLOSUM-FIRE, using MAFFT alignment as reference alignments has shown that it is more accurate than its predecessor FIRE. Comparison of the alignment quality with widely used algorithms (MUSCLE, T-COFFEE, and CLUSTAL Omega) revealed that the BLOSUM-FIRE algorithm performs as well as conventional algorithms. Its main strength lies in that it provides greater potential for aligning divergent sequences and addresses the problem of low specificity inherent in the original FIRE algorithm. The utility of this algorithm is demonstrated using the Hepatitis B virus X (HBx) protein, a protein of unknown function, as a test case. CONCLUSION: This study describes the utility of an evolutionary rate based approach coupled to the BLOSUM62 amino acid substitution matrix in inferring protein domain function. We demonstrate that such an approach is robust and performs as well as an array of conventional algorithms. PMID- 26269103 TI - Characterizing the physical and demographic variables associated with heavy metal distribution along urban-rural gradient. AB - This paper describes a study of how the demographic and physical variables affected the heavy metal (HM) contamination along the urban-rural gradient in PuDong New District, Shanghai. The road density (RDi) and the percentage of built up areas (BAi) were calculated for various widths of buffers around the soil sampling sites. Through distance allocation, the demographic values of the population change index (PCI) were assigned, with the value being associated with the nearest town. We initiated the use of the population migration rate from 2000 to 2010, i.e., PCI, to represent the urbanization rate. Regression analysis between the soil HM concentrations and the PCI, the RD, and the BA was estimated. The results indicated that the PCI significantly affected the Cd and Cu distribution (p < 0.05), while the RD of the 3-km buffer affected the Pb concentrations. The BA of 2-km buffers affected the spatial distribution of Cd, Cu, and Zn. Zn was also affected by the RD within the 4-km buffer. Using the median values of the PCI and the BA of the 2-km buffer, and the RD of the 3-km buffer, logistic analysis was performed to identify the priority areas for managing HM hazards. The two identified priority areas were the towns of Kangqiao and Zhuqiao, both of which were rapidly urbanized areas with higher PCI values. Our research demonstrated that understanding the rate of urbanization may be as important as the degree of urbanization when examining associated HM contamination patterns. PMID- 26269104 TI - Uncertainty assessment of heavy metal soil contamination mapping using spatiotemporal sequential indicator simulation with multi-temporal sampling points. AB - Mapping the space-time distribution of heavy metals in soils plays a key role in contaminated site classification under conditions of in situ uncertainty, whereas uncertainty assessment is based on the quantification of the specific uncertainties in terms of exceedance probabilities. Geostatistical space-time kriging (STK) is increasingly used to estimate pollutant concentrations in soils. Sequential indicator simulation (SIS) technique is popular in uncertainty assessment of heavy metal contamination of soils. However, these techniques cannot handle multi-temporal data. In this work, spatiotemporal sequential indicator simulation (STSIS) based on an additive space-time semivariogram model (STSIS_A) and on a non-separable space-time semivariogram model (STSIS_NS) was used to assimilate multi-temporal data in the mapping and uncertainty assessment of heavy metal distributions in contaminated soils. Cu concentrations in soils sampled during the period 2010-2014 in the Qingshan district (Wuhan City, Hubei Province, China) were used as the experimental data set. Based on a number of STSIS realizations, we assessed different kinds of mapping uncertainty, including single-location uncertainty during 1 year and during multiple years, multi location uncertainty during 1 year, and during multiple years. The comparison of the STSIS technique vs. SIS and STK techniques showed that STSIS performs better than both STK and SIS. PMID- 26269105 TI - A radon-thoron isotope pair as a reliable earthquake precursor. AB - Abnormal increases in radon ((222)Rn, half-life = 3.82 days) activity have occasionally been observed in underground environments before major earthquakes. However, (222)Rn alone could not be used to forecast earthquakes since it can also be increased due to diffusive inputs over its lifetime. Here, we show that a very short-lived isotope, thoron ((220)Rn, half-life = 55.6 s; mean life = 80 s), in a cave can record earthquake signals without interference from other environmental effects. We monitored (220)Rn together with (222)Rn in air of a limestone-cave in Korea for one year. Unusually large (220)Rn peaks were observed only in February 2011, preceding the 2011 M9.0 Tohoku-Oki Earthquake, Japan, while large (222)Rn peaks were observed in both February 2011 and the summer. Based on our analyses, we suggest that the anomalous peaks of (222)Rn and (220)Rn activities observed in February were precursory signals related to the Tohoku-Oki Earthquake. Thus, the (220)Rn-(222)Rn combined isotope pair method can present new opportunities for earthquake forecasting if the technique is extensively employed in earthquake monitoring networks around the world. PMID- 26269106 TI - I May be a Dinosaur but I'm not Pre-historic. PMID- 26269107 TI - Humic acid as promising organic anodes for lithium/sodium ion batteries. AB - As a representative natural polymer with abundant functionalities, humic acid was creatively explored as an anode material for lithium ion batteries and sodium ion batteries with high storage capacities, and satisfactory cycling stabilities. Most impressively, this work provides a promising and effective strategy for developing organic energy storage devices from natural sources. PMID- 26269108 TI - Pathways Forward in Cardiovascular Disease Prevention One and a Half Years After Publication of the 2013 ACC/AHA Cardiovascular Disease Prevention Guidelines. AB - The 2013 American College of Cardiology/American Heart Association cardiovascular disease prevention guidelines represent an important step forward in the risk assessment and management of atherosclerotic cardiovascular disease in clinical practice. Differentiated risk prediction equations for women and black individuals were developed, and convenient 10-year and lifetime risk assessment tools were provided, facilitating their implementation. Lifestyle modification was portrayed as the foundation of preventive therapy. In addition, based on high quality evidence from randomized controlled trials, statins were prioritized as the first lipid-lowering pharmacologic treatment, and a shared decision-making model between the physician and the patient was emphasized as a key feature of personalized care. After publication of the guidelines, however, important limitations were also identified. This resulted in a constructive scientific debate yielding valuable insights into potential opportunities to refine recommendations, fill gaps in guidance, and better harmonize recommendations within and outside the United States. The latter point deserves emphasis because when guidelines are in disagreement, this may result in nonaction on the part of professional caregivers or nonadherence by patients. In this review, we discuss the key scientific literature relevant to the guidelines published in the year and a half after their release. We aim to provide cohesive, evidence-based views that may offer pathways forward in cardiovascular disease prevention toward greater consensus and benefit the practice of clinical medicine. PMID- 26269109 TI - Influence of Temperature on the Formation of Silver Nanoparticles by using a Seed Free Photochemical Method under Sodium-Lamp Irradiation. AB - Silver nanoparticles can be prepared by using a seed-free photo-assisted citrate reduction method under the irradiation of a sodium lamp. Under the same irradiation intensity, bath temperatures are crucial in influencing the reaction rate, morphologies of final products, and shape evolution of the silver nanostructures. For example, when the bath temperature is 80 degrees C, the product yields of silver nanoplates, nanorods, and nanodecahedra are 38+/-6 %, 35+/-10 %, and 12+/-8 %, respectively. However, when the bath temperature is 30 degrees C, the product yields of silver nanoplates, nanorods, and nanodecahedra are 6+/-3 %, 0 %, and 83+/-16 %, respectively. Time-dependent UV/Vis spectra and TEM images show that silver nanoplates were formed at the earlier reaction stage and greatly decreased in amount at the later stage when the bath temperatures are less than or equal to 40 degrees C. This indicates that the silver nanoplates, which can be regarded as intermediates, are kinetically favored products. They are not thermodynamically favored products at these relatively low bath temperatures. The SERS spectra of crystal violet (CV) show that all the silver colloids synthesized at various temperatures exhibit good enhancement factors and that the colloids prepared at lower bath temperatures have a higher enhancement factor. PMID- 26269110 TI - Dry eye in vitamin D deficiency: more than an incidental association. AB - AIM: The aim of this article is two-fold: (i) to demonstrate the relation between vitamin D deficiency and dry eye and impaired tear function; and (ii) to investigate the possible associations among clinical parameters of hypovitaminosis D with dry eye parameters. METHOD: Fifty premenopausal women with vitamin D deficiency (serum vitamin D levels < 20 ng/mL) and 48 controls were included. Participants were assessed by Schirmer's test, tear break-up time test (TBUT), ocular surface disease index (OSDI), Stanford Health Assessment Questionnaire (HAQ), fatigue severity scale (FSS), and visual analogue scale-pain (VAS-pain). RESULTS: Lower scores in Schirmer's test and TBUT, and higher in OSDI were detected in patients with vitamin D deficiency than in controls (P < 0.05). FSS was negatively correlated with Schirmer's test (r = -0,29; P = 0.038) and TBUT scores (r = -0,43; P = 0.002); VAS-pain was negatively correlated with TBUT scores (r = -0.32; P = 0.023). HAQ scores showed no significant correlation with dry eye parameters (P > 0.05). Vitamin D level was negatively correlated with OSDI (r = -0.49; P < 0.001), and positively with Schirmer's test (r = 0.45; P = 0.001) and TBUT scores (r = 0.30; P = 0.029). CONCLUSION: Dry eye and impaired tear function in patients with vitamin D deficiency may indicate a protective role of vitamin D in the development of dry eye, probably by enhancing tear film parameters and reducing ocular surface inflammation. Patients with vitamin D deficiency should be evaluated for dry eye syndromes. PMID- 26269111 TI - Transcriptome Analysis of Invasive Plants in Response to Mineral Toxicity of Reclaimed Coal-Mine Soil in the Appalachian Region. AB - Efficient postmining reclamation requires successful revegetation. By using RNA sequencing, we evaluated the growth response of two invasive plants, goutweed (Aegopodium podagraria L.) and mugwort (Artemisia vulgaris), grown in two Appalachian acid-mine soils (MS-I and -II, pH ~ 4.6). Although deficient in macronutrients, both soils contained high levels of plant-available Al, Fe and Mn. Both plant types showed toxicity tolerance, but metal accumulation differed by plant and site. With MS-I, Al accumulation was greater for mugwort than goutweed (385 +/- 47 vs 2151 +/- 251 MUg g-1). Al concentration was similar between mine sites, but its accumulation in mugwort was greater with MS-I than MS II, with no difference in accumulation by site for goutweed. An in situ approach revealed deregulation of multiple factors such as transporters, transcription factors, and metal chelators for metal uptake or exclusion. The two plant systems showed common gene expression patterns for different pathways. Both plant systems appeared to have few common heavy-metal pathway regulators addressing mineral toxicity/deficiency in both mine sites, which implies adaptability of invasive plants for efficient growth at mine sites with toxic waste. Functional genomics can be used to screen for plant adaptability, especially for reclamation and phytoremediation of contaminated soils and waters. PMID- 26269112 TI - Preclinical evaluation of perifosine as a potential promising anti rhabdomyosarcoma agent. AB - Rhabdomyosarcoma (RMS) is a highly malignant and metastatic pediatric cancer that arises from the skeletal muscle. Recent studies have identified an important role of AKT signaling in RMS progression. In the current study, we investigated the activity of perifosine, an oral alkylphospholipid AKT inhibitor, against human RMS cells (RD and Rh-30 lines) both in vivo and in vitro, and studied the underlying mechanisms. We showed that perifosine significantly inhibited RMS cell growth in concentration- and time-dependent manners. Meanwhile, perifosine induced dramatic apoptosis in RMS cells. At the signaling level, perifosine blocked AKT activation, while inducing reactive oxygen species (ROS) production as well as JNK and P38 phosphorylations in RMS cells. Restoring AKT activation by introducing a constitutively active-AKT (CA-AKT) only alleviated (not abolished) perifosine-induced cytotoxicity in RD cells. Yet, the ROS scavenger N-acetyl cysteine (NAC) as well as pharmacological inhibitors against JNK (SP-600125) or P38 (SB-203580) suppressed perifosine-induced cytotoxicity in RMS cells. Thus, perifosine induces growth inhibition and apoptosis in RMS cells through mechanisms more than just blocking AKT. In vivo, oral administration of perifosine significantly inhibited growth of Rh-30 xenografts in severe combined immunodeficient (SCID) mice. Our data indicate that perifosine might be further investigated as a promising anti-RMS agent. PMID- 26269113 TI - TNIK serves as a novel biomarker associated with poor prognosis in patients with pancreatic cancer. AB - Traf-2 and Nck interacting kinase (TNIK) is one of the STE20/MAP4K family members implicated in carcinogenesis and progression of several human malignancies. However, its expression pattern and biological behavior in pancreatic carcinoma remains completely unclear. The present study is designed to investigate the clinical and prognostic value of TNIK in pancreatic carcinoma. TNIK mRNA and protein level was respectively detected by real-time quantitative RCR (qPCR) and Western blot in ten paired samples of pancreatic cancer. Immunohistochemical staining was also conducted to examine TNIK in the tissue microarray (TMA) consisting of 91 archived specimens of pancreatic cancer. The correlation between TNIK and prognosis was assessed by Kaplan-Meier curves and Cox regression. The mRNA and protein levels of TNIK in pancreatic cancer were both significantly higher than those in matched paratumor tissues. Immunohistochemistry analysis showed that TNIK was positively associated with pathologic T (P = 0.045) and TNM (P = 0.040) stage. In addition, The Kaplan-Meier survival curves indicated that patients with high expression of TNIK had a shorter overall survival (OS) and disease-free survival (DFS) than those with low expression. Our results demonstrated that TNIK might play a crucial role in pancreatic carcinogenesis and serve as a novel therapeutic target of pancreatic cancer. PMID- 26269114 TI - Polymorphisms in epidermal growth factor receptor (EGFR) and AKT1 as possible predictors of clinical outcome in advanced non-small-cell lung cancer patients treated with EGFR tyrosine kinase inhibitors. AB - This study aimed to investigate the association of epidermal growth factor receptor (EGFR) gene polymorphism and AKT1 polymorphism with the clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). The clinical outcome and the survival of NSCLC of 230 patients after treatment with EGFR-TKIs were measured. The rs712829, rs1468727 of the EGFR gene and rs1130214 of the AKT1 gene from peripheral blood cell were detected by a multiplexed single nucleotide polymorphism (SNP) MassEXTEND assay. The relationship between genetic polymorphisms and clinical outcomes of treatment with EGFR-TKIs was analyzed. The response rates and the disease control rate of patients with genotype GG, GT, and TT in EGFR rs712829 were statistically very significant difference(19.7 vs 36.1 vs 50.0 %, P = 0.016 and 57.7 vs 77.8 vs 83.3 %, P = 0.026, respectively). Better disease control was also achieved in patients with the GG genotype of AKT1 rs1130214 than those with the GT and TT genotypes (65.6 vs. 48.7 %, P = 0.043). Patients carrying the EGFR rs712829 TT genotype had significantly longer PFS and OS than those with the GT or GG genotypes (9.0 vs. 7.0 vs. 5.0 months, P = 0.001 and 13.1 vs. 14.6 vs. 18.8 months, P = 0.008, respectively). In addition, patients carrying the AKT1 rs1130214 GG genotype also had significantly longer PFS than those with the GT and TT genotypes (5.5 vs. 4.5 months, P = 0.008). EGFR rs712829 polymorphism and AKT1 rs1130214 could influence the response to EGFR TKIs therapy in patients with advanced NSCLC. PMID- 26269115 TI - Five miRNAs considered as molecular targets for predicting neuroglioma. AB - Neuroglioma is a complex neuroglial tumor involving dysregulation of many biological pathways at multiple levels. Here, we aim to screen differentially expressed miRNAs (DEMs) as well as the functions and pathways of their target genes in neuroglioma. miRNA high-throughput sequencing data were downloaded from The Cancer Genome Atlas (TCGA), and then the DEMs were subjected to perform principal component analysis (PCA) based on their expression values. Following that, Targetscan software was used to predict the target genes, and enrichment analysis and pathway annotation of these target genes were done by DAVID and KEGG, respectively. Finally, survival analysis between the DEMs and patients' survival time was done, and the miRNAs with prediction potential were obtained. A total of 33 DEMs were obtained, among which 25 miRNAs were upregulated including hsa-mir-675, hsa-mir-196a-1, and hsa-mir-196a-2, while eight miRNAs were downregulated including hsa-mir-1911, hsa-mir-1264, and hsa-mir-1298. Five miRNAs with diagnostic and preventive potentials were significantly correlated with survival time, including has-mir-155, has-mir-199b, has-mi-10a, has-mir-1274b, and has-mir-455. The target genes of miRNA identified in this study played important roles in tumor signaling pathways, and their detailed functions could be further studied so as to explore novel neuroglioma therapies. PMID- 26269116 TI - CDX2 inhibits pancreatic adenocarcinoma cell proliferation via promoting tumor suppressor miR-615-5p. AB - CDX2 has recently been identified as a prognostic marker for pancreatic adenocarcinoma. However, the role and mechanism of CDX2 in progression of pancreatic adenocarcinoma are still elusive. In this study, we observed that CDX2 expression was much lower in mouse pancreatic adenocarcinoma tissues and pancreatic cancer cells. A network integrated by ChIPBase platform hinted that miR-615-5p, a most newly discovered tumor suppressor, was probably bound by CDX2 in the promoter region. Chromatin immunoprecipitation (ChIP)-qPCR assay showed that CDX2 exhibited a high capacity of binding to miR-615-5p promoter region compared to the negative control. Real-time PCR and western blotting analyses revealed that CDX2 overexpression caused inflation of miR-615-5p and depression of insulin-like growth factor 2 (IGF2), a direct target of miR-615-5p. 3-(4,5 Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and EdU approaches showed that CDX2 overexpression markedly suppressed pancreatic adenocarcinoma cell proliferation. CDX2 small interfering RNA (siRNA) transfection showed an opposite effect on gene expression and cell proliferation to that of CDX2 overexpression. Collectively, CDX2 inhibited pancreatic adenocarcinoma cell proliferation via promoting tumor suppressor miR-615-5p. Our findings suggested a potential molecular target for pancreatic adenocarcinoma therapy. PMID- 26269117 TI - Ataxia-telangiectasia mutated (ATM) participates in the regulation of ionizing radiation-induced cell death via MAPK14 in lung cancer H1299 cells. AB - OBJECTIVES: The role of Ataxia-telangiectasia mutated (ATM) in response to DNA damage has previously been studied, but its underlying mechanisms specific to ionizing radiation (IR) have remained to be elucidated. In this study, function of ATM on radiation-induced cell death in lung cancer H1299 cells was analysed. MATERIALS AND METHODS: Human lung cancer cells, H1299, were used, and cell models with ATM(-/-) and MAPK14(-/-) were established by genetic engineering. Radiosensitivity was analysed using colony formation assays. Western blotting and co-immunoprecipitation were implemented to detect protein expression and interaction. MDC staining and GFP-LC3 relocalization were used to detect autophagy. RESULTS: Autophagy as well as phosphorylation of ATM was activated by ionizing radiation. Both the inhibitor of ATM, KU55933 and ATM silencing reduced phosphorylation of ATM and MAPKAPK2 expression. Both ATM(-/-) and MAPK14(-/-) cells displayed hypersensitivity. IR increased autophagy level by more than 129% in DMSO-treated cells, while only by 47% and 27% in KU55933-treated and ATM(-/-) cells respectively. MAPK14 knock-down alone gave rise to the basal autophagy level, but decreased notably after IR. KU55933 and ATM knock-down inhibited IR induced autophagy by activating mTOR pathways. Both Beclin1-PI3KIII and Beclin1 MAPKAPK2 interactions as were remarkably affected by silencing either ATM or MAPK14. CONCLUSIONS: ATM promoted IR-induced autophagy via the MAPK14 pathway, mTOR pathway and Beclin1/PI3KIII complexes. MAPK14 contributed to radiosensitization of H1299 cells. PMID- 26269118 TI - Comparison of serious adverse events posted at ClinicalTrials.gov and published in corresponding journal articles. AB - BACKGROUND: The reporting of serious adverse events (SAEs) in clinical trials is crucial to assess the balance between benefits and risks. For trials with serious adverse events posted at ClinicalTrials.gov, we assessed the consistency between SAEs posted at ClinicalTrials.gov and those published in corresponding journal articles. METHODS: All records from ClinicalTrials.gov up to February 2014 were automatically exported in XML format. Among these, we identified all phase III or IV randomized controlled trials with at least one SAE posted. For a random sample of 300 of these trials, we searched for corresponding publications using MEDLINE via PubMed and extracted safety results from the articles. RESULTS: Among the sample of 300 trials with SAEs posted at ClinicalTrials.gov, 78 (26%) did not have a corresponding publication, and 20 (7%) had a publication that did not match the ClinicalTrials.gov record. For the 202 remaining trials, 26 published articles (13%) did not mention SAEs, 4 (2%) reported no SAEs, and 33 (16%) did not report the total number of SAEs per treatment group. Among the remaining 139 trials, for 44 (32%), the number of SAEs per group published did not match those posted at ClinicalTrials.gov. For 31 trials, the number of SAEs was greater at ClinicalTrials.gov than in the published article, with a difference >=30 % for at least one group for 21. Only 33 trials (11%) had a publication reporting matching numbers of SAE and describing the type of SAE. CONCLUSIONS: Many trials with SAEs posted at ClinicalTrials.gov are not yet published, omit the reporting of these SAEs in corresponding publications, or report a discrepant number of SAEs as compared with ClinicalTrials.gov. These results underline the need to consult ClinicalTrials.gov for more information on serious harms. PMID- 26269119 TI - Natural variants of ELF3 affect thermomorphogenesis by transcriptionally modulating PIF4-dependent auxin response genes. AB - BACKGROUND: Perception and transduction of temperature changes result in altered growth enabling plants to adapt to increased ambient temperature. While PHYTOCHROME-INTERACTING FACTOR4 (PIF4) has been identified as a major ambient temperature signaling hub, its upstream regulation seems complex and is poorly understood. Here, we exploited natural variation for thermo-responsive growth in Arabidopsis thaliana using quantitative trait locus (QTL) analysis. RESULTS: We identified GIRAFFE2.1, a major QTL explaining ~18 % of the phenotypic variation for temperature-induced hypocotyl elongation in the Bay-0 x Sha recombinant inbred line population. Transgenic complementation demonstrated that allelic variation in the circadian clock regulator EARLY FLOWERING3 (ELF3) is underlying this QTL. The source of variation could be allocated to a single nucleotide polymorphism in the ELF3 coding region, resulting in differential expression of PIF4 and its target genes, likely causing the observed natural variation in thermo-responsive growth. CONCLUSIONS: In combination with other recent studies, this work establishes the role of ELF3 in the ambient temperature signaling network. Natural variation of ELF3-mediated gating of PIF4 expression during nightly growing periods seems to be affected by a coding sequence quantitative trait nucleotide that confers a selective advantage in certain environments. In addition, natural ELF3 alleles seem to differentially integrate temperature and photoperiod information to induce architectural changes. Thus, ELF3 emerges as an essential coordinator of growth and development in response to diverse environmental cues and implicates ELF3 as an important target of adaptation. PMID- 26269120 TI - Reduction of Airborne Bacterial Burden in the OR by Installation of Unidirectional Displacement Airflow (UDF) Systems. AB - BACKGROUND: Intraoperative bacterial contamination is a major risk factor for postoperative wound infections. This study investigated the influence of type of ventilation system on intraoperative airborne bacterial burden before and after installation of unidirectional displacement air flow systems. MATERIAL AND METHODS: We microbiologically monitored 1286 surgeries performed by a single surgical team that moved from operating rooms (ORs) equipped with turbulent mixing ventilation (TMV, according to standard DIN-1946-4 [1999], ORs 1, 2, and 3) to ORs with unidirectional displacement airflow (UDF, according to standard DIN-1946-4, annex D [2008], ORs 7 and 8). The airborne bacteria were collected intraoperatively with sedimentation plates. After incubation for 48 h, we analyzed the average number of bacteria per h, peak values, and correlation to surgery duration. In addition, we compared the last 138 surgeries in ORs 1-3 with the first 138 surgeries in ORs 7 and 8. RESULTS: Intraoperative airborne bacterial burden was 5.4 CFU/h, 5.5 CFU/h, and 6.1 CFU/h in ORs 1, 2, and 3, respectively. Peak values of burden were 10.7 CFU/h, 11.1 CFU/h, and 11.0 CFU/h in ORs 1, 2, and 3, respectively). With the UDF system, the intraoperative airborne bacterial burden was reduced to 0.21 CFU/h (OR 7) and 0.35 CFU/h (OR 8) on average (p<0.01). Accordingly, peak values decreased to 0.9 CFU/h and 1.0 CFU/h in ORs 7 and 8, respectively (p<0.01). Airborne bacterial burden increased linearly with surgery duration in ORs 1-3, but the UDF system in ORs 7 and 8 kept bacterial levels constantly low (<3 CFU/h). A comparison of the last 138 surgeries before with the first 138 surgeries after changing ORs revealed a 94% reduction in average airborne bacterial burden (5 CFU/h vs. 0.29 CFU/h, p<0.01). CONCLUSIONS: The unidirectional displacement airflow, which fulfills the requirements of standard DIN-1946-4 annex D of 2008, is an effective ventilation system that reduces airborne bacterial burden under real clinical conditions by more than 90%. Although decreased postoperative wound infection incidence was not specifically assessed, it is clear that airborne microbiological burden contributes to surgical infections. PMID- 26269121 TI - Acral keratoses and leucocytoclastic vasculitis occurring during treatment of essential thrombocythaemia with hydroxyurea. AB - Hydroxyurea is used in essential thrombocythaemia to lower thromboembolic risk. Cutaneous adverse effects from hydroxyurea are diverse. Small vessel vasculitis has been rarely reported, and the coexistence of several different morphologies has not been described. We report a case of acral keratoses, psoriasiform plaques and leucocytoclastic vasculitis (LCV) in a patient with essential thrombocythaemia. A 69-year-old woman developed a confusing array of skin lesions including keratotic papules, psoriasiform plaques and keratoderma 4 years after commencing hydroxyurea therapy. The initial diagnosis was hand and foot psoriasis, but lesions were resistant to therapy. With an increase in the dose of hydroxyurea, the lesions ulcerated. Skin biopsies taken from different sites indicated different diagnoses, including LCV. Discontinuation of hydroxyurea yielded rapid improvement. Although the most commonly reported cutaneous adverse effect from hydroxyurea is leg ulceration, this can be preceded or accompanied by less dramatic skin lesions. Unless recognized, delayed diagnosis and lesion progression can occur. PMID- 26269123 TI - Pregnane X receptor expression in skin: the good and the bad. PMID- 26269122 TI - Psychometric Properties of Self-Care Requisites Scale (SCRS-h) in Hospitalized Patients Diagnosed With Schizophrenia. AB - PURPOSE: The purpose of this study was to adapt the community version of the Self Care Requisites Scale so as to be able to use it in a hospital context and to validate the new version in patients with schizophrenia. DESIGN AND METHODS: An initial phase was conducted to develop the questionnaire by means of a panel of experts. The validation of the psychometric properties was conducted using a sample of 264 patients. FINDINGS: The new version showed good internal consistency and stability over time. The confirmatory factor analysis showed that the theoretical model fit the self-care requisites proposed in Orem's nursing theory from which it was drawn. PRACTICE IMPLICATIONS: The new version is a valid and reliable instrument for use in clinical practice. PMID- 26269124 TI - Fatal co-infection with leptospirosis and dengue in a Sri Lankan male. AB - BACKGROUND: Leptospirosis and dengue are endemic in countries with subtropical or tropical climates and have epidemic potential. The incidence of both these diseases peaks during monsoons and both diseases present with similar clinical manifestations making differentiation of leptospirosis from dengue difficult. It is important to distinguish leptospirosis from dengue as early antibiotic therapy in leptospirosis leads to a favourable outcome, while dengue has no specific treatment, yet early recognition is vital for close monitoring and careful fluid management. Despite the high prevalence of both these infections, co-infection of leptospirosis and dengue has not been reported previously in Sri Lanka. We present the first case of co-infection with leptospirosis and dengue in a Sri Lankan male. CASE PRESENTATION: A 52 year old previously healthy Sri Lankan male was admitted to our facility with a history of fever for 4 days associated with headache, generalized myalgia, reduced urine output. On examination, he was rational, hypotensive, tacycardic, tacypneic and he did not have clinical evidence of fluid leakage or pneumonitis. His serology showed high titre of dengue IgG and IgM and rising titre of leptospirosis antibody. His course of illness was complicated with septic shock, acute renal failure, acute respiratory distress syndrome and disseminated intravascular coagulation and he succumbed to his illness on the eighth day of admission. CONCLUSION: In areas where both leptospirosis and dengue are endemic, both infections should be include in the differential diagnosis when evaluating patients with acute febrile illness and should consider the possibility of co-infection. Leptospirosis, being a condition having definitive antibiotic therapy, should always be ruled out even if the patient is positive for dengue serology in regions endemic to both these diseases as early initiation of antibiotic therapy can reduce mortality significantly. PMID- 26269125 TI - The effect of succinate dehydrogenase inhibitor/azole mixtures on selection of Zymoseptoria tritici isolates with reduced sensitivity. AB - BACKGROUND: Combining fungicides with different modes of action is regarded as one of the most effective means of slowing the selection of resistance. Field trials were used to study the effects of such mixtures on selection for Zymoseptoria tritici with reduced sensitivity to the succinate dehydrogenase inhibitors (SDHIs) and azole fungicides. The SDHI isopyrazam and the azole epoxiconazole were applied individually as solo products, and together in a preformulated mixture. All fungicide treatments were included at both full and half the recommended doses. RESULTS: Compared with using epoxiconazole alone, mixing epoxiconazole with isopyrazam led to an increase in epoxiconazole sensitive isolates. In contrast, all treatments containing isopyrazam reduced the sensitivity of Z. tritici to isopyrazam compared with those without. Reducing doses to half the recommended rate had no effect on sensitivity of isolates to either active ingredient. In a subgroup of isolates least sensitive to isopyrazam, non-synonymous mutations were found in the SdhC and SdhD subunits, but their presence was unrelated to sensitivity. CONCLUSION: Mixing an azole and SDHI was clearly beneficial for the azole, but not for the SDHI component. This dynamic might change if strains conferring reduced sensitivity to the SDHIs were to arise. (c) 2015 Society of Chemical Industry. PMID- 26269127 TI - Corrigendum. PMID- 26269126 TI - Somatic drivers of B-ALL in a model of ETV6-RUNX1; Pax5(+/-) leukemia. AB - BACKGROUND: B-cell precursor acute lymphoblastic leukemia (B-ALL) is amongst the leading causes of childhood cancer-related mortality. Its most common chromosomal aberration is the ETV6-RUNX1 fusion gene, with ~25% of ETV6-RUNX1 patients also carrying PAX5 alterations. METHODS: We have recreated this mutation background by inter-crossing Etv6-RUNX1 (Etv6 (RUNX1-SB)) and Pax5(+/-) mice and performed an in vivo analysis to find driver genes using Sleeping Beauty transposon-mediated mutagenesis and also exome sequencing. RESULTS: Combination of Etv6-RUNX1 and Pax5(+/-) alleles generated a transplantable B220 + CD19+ B-ALL with a significant disease incidence. RNA-seq analysis showed a gene expression pattern consistent with arrest at the pre-B stage. Analysis of the transposon common insertion sites identified genes involved in B-cell development (Zfp423) and the JAK/STAT signaling pathway (Jak1, Stat5 and Il2rb), while exome sequencing revealed somatic hotspot mutations in Jak1 and Jak3 at residues analogous to those mutated in human leukemias, and also mutation of Trp53. CONCLUSIONS: Powerful synergies exists in our model suggesting STAT pathway activation and mutation of Trp53 are potent drivers of B-ALL in the context of Etv6 RUNX1;Pax5(+/-). PMID- 26269128 TI - The Regulation and Function of Lactate Dehydrogenase A: Therapeutic Potential in Brain Tumor. AB - There are over 120 types of brain tumor and approximately 45% of primary brain tumors are gliomas, of which glioblastoma multiforme (GBM) is the most common and aggressive with a median survival rate of 14 months. Despite progress in our knowledge, current therapies are unable to effectively combat primary brain tumors and patient survival remains poor. Tumor metabolism is important to consider in therapeutic approaches and is the focus of numerous research investigations. Lactate dehydrogenase A (LDHA) is a cytosolic enzyme, predominantly involved in anaerobic and aerobic glycolysis (the Warburg effect); however, it has multiple additional functions in non-neoplastic and neoplastic tissues, which are not commonly known or discussed. This review summarizes what is currently known about the function of LDHA and identifies areas that would benefit from further exploration. The current knowledge of the role of LDHA in the brain and its potential as a therapeutic target for brain tumors will also be highlighted. The Warburg effect appears to be universal in tumors, including primary brain tumors, and LDHA (because of its involvement with this process) has been identified as a potential therapeutic target. Currently, there are, however, no suitable LDHA inhibitors available for tumor therapies in the clinic. PMID- 26269129 TI - The prevalence and outcomes of pT0 disease after neoadjuvant hormonal therapy and radical prostatectomy in high-risk prostate cancer. AB - BACKGROUND: To identify the prevalence and clinical outcomes of pT0 disease following neoadjuvant hormonal therapy (NHT) and radical prostatectomy (RP) in high-risk prostate cancer. METHODS: We retrospectively included 111 patients who had received NHT and RP for the treatment of high-risk prostate cancer. We classified the patients into two groups, the pT0 group and the non-pT0 group, depending on whether a residual tumor was observed. RESULTS: We identified 6 cases (5.4%) with pT0 disease after reviewing the slides of all patients. There was no recurrence of disease in the pT0 group during a median follow-up of 59 months. Among the 105 patients in the non-pT0 group, biochemical recurrence (BCR) developed in 60 patients (57.1%), with the median time to BCR being 14 months. CONCLUSIONS: Among the 111 patients with high-risk prostate cancer, we found 6 cases that showed a complete pathological response after NHT and no recurrence of disease during the follow-up, meaning that the androgen deprivation therapy could potentially eradicate high-risk prostate cancer. This is one of the largest studies demonstrating the prevalence of pT0 disease and its outcomes after NHT among patients with high-risk prostate cancer. PMID- 26269130 TI - Screening and Follow-Up Monitoring for Substance Use in Primary Care: An Exploration of Rural-Urban Variations. AB - BACKGROUND: Rates of substance use in rural areas are close to those of urban areas. While recent efforts have emphasized integrated care as a promising model for addressing workforce shortages in providing behavioral health services to those living in medically underserved regions, little is known on how substance use problems are addressed in rural primary care settings. OBJECTIVE: To examine rural-urban variations in screening and monitoring primary care- based patients for substance use problems in a state-wide mental health integration program. DESIGN: This was an observational study using patient registry. SUBJECTS: The study included adult enrollees (n = 15,843) with a mental disorder from 133 participating community health clinics. MAIN OUTCOMES: We measured whether a standardized substance use instrument was used to screen patients at treatment entry and to monitor symptoms at follow-up visits. KEY RESULTS: While on average 73.6 % of patients were screened for substance use, follow-up on substance use problems after initial screening was low (41.4 %); clinics in small/isolated rural settings appeared to be the lowest (13.6 %). Patients who were treated for a mental disorder or substance abuse in the past and who showed greater psychiatric complexities were more likely to receive a screening, whereas patients of small, isolated rural clinics and those traveling longer distances to the care facility were least likely to receive follow-up monitoring for their substance use problems. CONCLUSIONS: Despite the prevalent substance misuse among patients with mental disorders, opportunities to screen this high-risk population for substance use and provide a timely follow-up for those identified as at risk remained overlooked in both rural and urban areas. Rural residents continue to bear a disproportionate burden of substance use problems, with rural-urban disparities found to be most salient in providing the continuum of services for patients with substance use problems in primary care. PMID- 26269132 TI - Live birth rates after IVF are lower with frozen donor eggs, study shows. PMID- 26269131 TI - Patients' Satisfaction with and Preference for Telehealth Visits. AB - BACKGROUND: One-quarter of U.S. patients do not have a primary care provider or do not have complete access to one. Work and personal responsibilities also compete with finding convenient, accessible care. Telehealth services facilitate patients' access to care, but whether patients are satisfied with telehealth is unclear. OBJECTIVE: We assessed patients' satisfaction with and preference for telehealth visits in a telehealth program at CVS MinuteClinics. DESIGN: Cross sectional patient satisfaction survey. PARTICIPANTS: Patients were aged >=18 years, presented at a MinuteClinic offering telehealth in January-September 2014, had symptoms suitable for telehealth consultation, and agreed to a telehealth visit when the on-site practitioner was busy. MAIN MEASURES: Patients reported their age, gender, and whether they had health insurance and/or a primary care provider. Patients rated their satisfaction with seeing diagnostic images, hearing and seeing the remote practitioner, the assisting on-site nurse's capability, quality of care, convenience, and overall understanding. Patients ranked telehealth visits compared to traditional ones: better (defined as preferring telehealth), just as good (defined as liking telehealth), or worse. Predictors of preferring or liking telehealth were assessed via multivariate logistic regression. KEY RESULTS: In total, 1734 (54 %) of 3303 patients completed the survey: 70 % were women, and 41 % had no usual place of care. Between 94 and 99 % reported being "very satisfied" with all telehealth attributes. One-third preferred a telehealth visit to a traditional in-person visit. An additional 57 % liked telehealth. Lack of medical insurance increased the odds of preferring telehealth (OR = 0.83, 95 % CI, 0.72-0.97). Predictors of liking telehealth were female gender (OR = 1.68, 1.04-2.72) and being very satisfied with their overall understanding of telehealth (OR = 2.76, 1.84-4.15), quality of care received (OR = 2.34, 1.42-3.87), and telehealth's convenience (OR = 2.87, 1.09-7.94) CONCLUSIONS: Patients reported high satisfaction with their telehealth experience. Convenience and perceived quality of care were important to patients, suggesting that telehealth may facilitate access to care. PMID- 26269133 TI - Mapping molecules in scanning far-field fluorescence nanoscopy. AB - In fluorescence microscopy, the distribution of the emitting molecule number in space is usually obtained by dividing the measured fluorescence by that of a single emitter. However, the brightness of individual emitters may vary strongly in the sample or be inaccessible. Moreover, with increasing (super-) resolution, fewer molecules are found per pixel, making this approach unreliable. Here we map the distribution of molecules by exploiting the fact that a single molecule emits only a single photon at a time. Thus, by analysing the simultaneous arrival of multiple photons during confocal imaging, we can establish the number and local brightness of typically up to 20 molecules per confocal (diffraction sized) recording volume. Subsequent recording by stimulated emission depletion microscopy provides the distribution of the number of molecules with subdiffraction resolution. The method is applied to mapping the three-dimensional nanoscale organization of internalized transferrin receptors on human HEK293 cells. PMID- 26269134 TI - Correlates of Sun Safety Practices in a Racially and Ethnically Diverse Sample of Adolescents: Implications for Skin Cancer Prevention Interventions. AB - To guide skin cancer preventive interventions, this study examined correlates of sun safety behaviors in a racially and ethnically diverse sample of 407 adolescents completing a self-report survey at the time of their pediatric wellness visit. Adolescents regularly practiced few sun safety behaviors, and greater interest in cancer prevention was associated with more sun safety behaviors, ever smoking cigarettes was associated with fewer sun safety behaviors, and nonwhite minority adolescents practiced fewer sun safety behaviors than non-Hispanic whites. Clinical preventive interventions to increase sun safety practices among adolescents of all racial and ethnic backgrounds could be integrated into general cancer prevention education, including combining skin cancer prevention with antismoking counseling. PMID- 26269135 TI - Association between lower frequency of R381Q variant (rs11209026) in IL-23 receptor gene and increased risk of recurrent spontaneous abortion (RSA). AB - Recurrent spontaneous abortion (RSA) is defined as three or more consecutive spontaneous abortions before the 20th week of gestation. The purpose of the present study was to investigate the association between a functional single nucleotide polymorphism (SNP) in the interleukin (IL)-23 receptor gene (IL-23R; rs11209026, 1142 G wild type -> A reduced function, Arg381Gln, R381Q) and RSA. For the study, 200 RSA patients (confirmed using established diagnostic criteria) and 200 normal individuals in fertility and infertility centers in the cities of Yazd and Isfahan were recruited during a period from 2012-2013. Using PCR-RFLP, the R381Q variant was screened for in the IL-23R gene of the patients and controls. The results indicated there were significant differences in the frequency of this genetic variant in the patients versus the healthy controls, i.e. 2% and 7.5%, respectively (p value = 0.01; odds ratio = 0.25; CI = 95%). No significant difference was found for the G allelic frequency in patients with RSA and in the control group (p = 0.60). The A allelic frequency was significantly different between the two groups (p = 0.01). Based on these findings, it is concluded that the frequency of single nucleotide polymorphism in the IL-23 receptor (R381Q) in patients with recurrent spontaneous abortion (RSA) is less than that found in normal control women. PMID- 26269136 TI - Immune function in cyclophosphamide-treated mice is restored by the T-cell-tropic isoxazole derivative R-13. AB - Reconstitution of the immune function in chemotherapy patients will lead to decreases in post-operative complications. A preliminary investigation showed that an isoxazole derivative R-13 (3,5-dimethyl-isoxazole[5,4-e]8H-triazepin-4 one) hydrochloride, given in a single oral dose to normal mice, induced significant increases in the content of CD4(+) cells in the spleens and lymph nodes. That observation prompted the authors to assess the immune reconstituting effects of R-13 in mice pre-treated with cyclophosphamide (CP). Mice were given intraperitoneally (IP) a sublethal dose of CP (200 mg/kg) and then R-13 (as 20 ug IP doses, every 3 days post-CP treatment). Control mice, not treated with CP, received R-13 or the vehicle (DMSO in appropriate dilution). Blood leukocyte and splenocyte numbers, blood cell type levels, splenocyte spontaneous and ConA induced proliferation, and delayed-type hypersensitivity (DTH) to ovalbumin (OVA) were investigated on day 15 post-CP treatment and five R-13 doses. The humoral immune response (antibody-forming cell development to sheep erythrocytes) was measured 30 days post-CP treatment and 10 R-13 doses. In CP-treated mice, five dosings with R-13 led to increases in numbers of splenocytes and blood leukocytes, as well as in spontaneous and ConA-induced splenocyte proliferation, relative to levels in mice that received only CP 15 days earlier. Blood analysis revealed decreases in neutrophil and eosinophil contents and an increased appearance of lymphocyte immature forms in all mice that received the R-13. Both cell-mediated responses to OVA and humoral immune response to sheep erythrocytes in CP-treated hosts were restored. Based on the data here, it is concluded that R 13 may be of potential value for reconstitution of the immune function of chemotherapy patients. PMID- 26269137 TI - Improving Objective Measurement in Nursing Research: Rasch Model Analysis and Diagnostics of the Nursing Students' Clinical Stress Scale. AB - BACKGROUND AND PURPOSE: The purpose of this study is to use Rasch model diagnostics and analysis to understand survey item (questions) functioning of the Nursing Students' Clinical Stress Scale, a rating scale instrument developed by Whang (2002). METHODS: A rating scale instrument originally written in Korean was translated into English and administered to a convenience sample of all junior (46) and senior (64) students at a large Midwest university. RESULTS AND CONCLUSIONS: Rasch model analysis provided the empirical evidence to support that the survey items measured the latent variable, stress. Diagnostic results indicated the need for improved category labeling. CLINICAL RELEVANCE: It is imperative that nursing educators evaluate and facilitate inter- and intraprofessional relationships between students and staff/faculty as well as understand the student experience. PMID- 26269138 TI - Validity of the French Version of the Reynolds Empathy Scale Among Intensive Care Nurses. AB - BACKGROUND AND PURPOSE: Empathy is an important part of the nurse-patient relationship. The aim was to validate the French version of the Reynolds Empathy Scale (F-RES) for assessing empathy in nurses during standardized clinical simulations (SCS). METHODS: A series of steps recommended for the translation and validation of an instrument was carried out. Then the F-RES was used to assess empathy during SCS sessions with 26 nurses. RESULTS: The results showed good internal consistency and inter-rater reliability of the F-RES. The expert panel was satisfied with the content and face validity of the instrument. Convergent validity was confirmed using the French version of the Jefferson Scale of Patient Perceptions of Physician Empathy. CONCLUSIONS: The F-RES has good psychometric qualities and potential for future research in French populations. PMID- 26269139 TI - Psychometric Testing of the Autonomy and Relatedness Inventory-Spanish Version. AB - BACKGROUND AND PURPOSE: The Hispanic population is the fastest growing ethnic group in the United States. There is a lack of validated health-related tools culturally and linguistically appropriate. The purpose of this study was to evaluate the psychometric properties of the Autonomy and Relatedness Inventory Spanish version (ARI-S). METHODS: We recruited a convenience sample of 100 pregnant Hispanic women. RESULTS: Cronbach's alpha for the ARI-S total scale was .92. Factor analysis yielded a similar factor structure as reported with the ARI English version. As hypothesized, the ARI-S was inversely correlated with depressive symptoms and positively correlated with social support. CONCLUSIONS: ARI-S provides a psychometrically sound method for measuring the quality of intimate relationships. This is particularly important considering the limited inclusion of Hispanic women in current research. PMID- 26269140 TI - Teaching Behavior Inventory at the College of Nursing, Qassim University, Kingdom of Saudi Arabia: A Comparative Survey. AB - BACKGROUND AND PURPOSE: Teaching is one of the most complicated jobs today. Students and teachers may have different views depending on their background, styles, goals, and needs. This study aims to determine and compare the inventory of teaching behavior as rated by students and teachers. METHODS: A questionnaire formulated by Murray (1983) and modified by the researchers was administered to 56 students and 12 teachers at the College of Nursing of Qassim University. The response rate was 85.3%. RESULTS: Differences in ranking were not significant on enthusiasm, pacing, interaction, rapport, and clarity. High statistical significance was found in organization and speech. A remarkable difference in ranking was obtained in disclosure. CONCLUSIONS: Various factors are associated with the students' and faculty's views of effective teaching behaviors. PMID- 26269141 TI - Characterizing the Long-Term PM2.5 Concentration-Response Function: Comparing the Strengths and Weaknesses of Research Synthesis Approaches. AB - The magnitude, shape, and degree of certainty in the association between long term population exposure to ambient fine particulate matter (PM2.5 ) and the risk of premature death is one of the most intensely studied issues in environmental health. For regulatory risk analysis, this relationship is described quantitatively by a concentration-response (C-R) function that relates exposure to ambient concentrations with the risk of premature mortality. Four data synthesis techniques develop the basis for, and derive, this function: systematic review, expert judgment elicitation, quantitative meta-analysis, and integrated exposure-response (IER) assessment. As part of an academic workshop aiming to guide the use of research synthesis approaches, we developed criteria with which to evaluate and select among the approaches for their ability to inform policy choices. These criteria include the quality and extent of scientific support for the method, its transparency and verifiability, its suitability to the policy problem, and the time and resources required for its application. We find that these research methods are both complementary and interdependent. A systematic review of the multidisciplinary evidence is a starting point for all methods, providing the broad conceptual basis for the nature, plausibility, and strength of the associations between PM exposure and adverse health effects. Further, for a data-rich application like PM2.5 and premature mortality, all three quantitative approaches can produce estimates that are suitable for regulatory and benefit analysis. However, when fewer data are available, more resource intensive approaches such as expert elicitation may be more important for understanding what scientists know, where they agree or disagree, and what they believe to be the most important areas of uncertainty. Whether implicitly or explicitly, all require considerable judgment by scientists. Finding ways for all these methods to acknowledge, appropriately elicit, and examine the implications of that judgment would be an important step forward for research synthesis. PMID- 26269142 TI - Is Helicobacter pylori infection a critical risk factor for vascular dementia? AB - PURPOSE: The association of Helicobacter pylori (Hp) infection and Alzheimer's disease has widely been addressed, but no relative data exist regarding vascular dementia (VD). The purpose of this study was to evaluate the relationship between Hp infection and VD. MATERIAL AND METHOD: From January 2014 to March 2015, patients at Tai'an City Central Hospital who were diagnosed with VD were included. Patients were divided into Hp positive and Hp negative group using the (13)C-urea breath test ((13)C-UBT). Three inflammatory cytokines including interleukin-1 beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) were detected. RESULTS: A total of 173 VD patients were included in the study. According to (13)C-UBT, 104 patients (60.1%) were Hp positive VD patients and 69 patients (39.9%) were Hp negative patients. No differences were found between Hp positive and Hp negative patients as regard to age, gender, body mass index, education level, hypertension, diabetes mellitus and hyperlipidemia (p > 0.05). Hp positive patients demonstrated significantly lower mean mini-mental state examination and Montreal cognitive assessment scores (p < 0.05) and higher plasma levels of IL-1beta, IL-6 and TNF-alpha than Hp negative patients (p < 0.05). CONCLUSIONS: Hp infection might contribute, at least in part, to the cognitive decline in patients with VD, and play a critical role possibly through increasing expression of IL-1beta, IL-6 and TNF-alpha. PMID- 26269143 TI - Retinal Nerve Fiber Layer Thickness Changes in Migraine: A Meta-Analysis of Case Control Studies. AB - BACKGROUND: The neurovascular dysfunction appears to be related to the development of migraines and it could be possible that hypoperfusion might also involve other areas besides brain, including the retina. Numerous studies have analyzed the ability of optical coherence tomography (OCT) to detect retinal nerve fiber layer (RNFL) thickness abnormalities and changes in migraine, but the results have not always been consistent. Therefore, we carried out a meta analysis to evaluate the RNFL thickness measured with OCT in migraine. METHODS: Case-control studies were selected through an electronic search of the Cochrane Controlled Trials Register, PUBMED and EMBASE. For the continuous outcomes, we calculated the weighted mean difference (WMD) and 95% confidence interval (CI). The statistical analysis was performed by RevMan 5.0 software. RESULTS: Six case control studies were included in the present meta-analysis, containing a total of 432 eyes in migraine patients and 288 eyes in healthy controls. The results of our study showed that there was a significant reduction in average RNFL thickness in patients with migraine compared to healthy controls (WMD = -3.67, 95% CI: 6.84 to -0.49, p = 0.02). Additionally, differences of RNFL thickness in superior quadrant (WMD = -9.23, 95% CI: -15.63 to -2.82, p = 0.005), inferior quadrant (WMD = -3.47, 95% CI: -6.73 to -0.22, p = 0.04), nasal quadrant (WMD = -3.86, 95% CI: -7.10 to -0.61, p = 0.02) and temporal quadrant (WMD = -3.10, 95% CI: -5.05 to -1.15, p = 0.002) were all significant between the two groups. CONCLUSIONS: Our meta-analysis found that RNFL thickness in the migraine patients was thinner than that in the healthy control group. Given the limited sample size, further investigations are needed to validate these findings. PMID- 26269144 TI - The Janus-Faced Role of Aryl Hydrocarbon Receptor Signaling in the Skin: Consequences for Prevention and Treatment of Skin Disorders. AB - The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor expressed in all skin cell types, which is critically involved in the pathogenesis of a variety of skin diseases and thus represents a potential therapeutic target. Recent studies indicate that blocking AHR activation is desirable in some skin conditions, whereas the opposite, i.e., stimulation of AHR activation, is beneficial in another group of skin disorders. We here propose a model based on qualitative differences in canonical versus non-canonical AHR signaling to reconcile these seemingly contradictory observations. PMID- 26269145 TI - Activity of Porophyllum ruderale leaf extract and 670-nm InGaP laser during burns repair in rats. AB - BACKGROUND: In this study, we investigated the effects of an extract of the leaves of Porophyllum ruderale and laser irradiation on the healing of burns. METHODS: Seventy-two rats were divided in four groups: untreated controls, treated with laser irradiation, treated with P. ruderale and treated with both P. ruderale and laser irradiation. Burns were produced with a metal plate on the backs of the animals. Wound samples were collected for structural and morphometric analyses and to quantify the expression of TGF-beta1 and VEGF. RESULTS: Laser irradiation increased the number of fibroblasts, collagen fibers and newly formed vessels and decreased the number of granulocytes at the site of the wounds. Densitometric analysis revealed a significant increase in the expression of TGFbeta-1 in the wounds treated with laser irradiation and with the P. ruderale extract at the beginning of the healing process and a decreased during the experimental period. The expression of VEGF was highlighted in the lesions irradiated with laser alone. CONCLUSION: Inspite of not showing a beneficial effect on the laser combination with the P. ruderale extract, when the laser was used separately, a positive effects to enhance the healing of second degree burns was promoted. P. ruderale was effective in decreasing the granulocytes during the repair process indicating a possible anti-inflammatory action of this extract of native flora, widely used in folk medicine, but little studied experimentally. PMID- 26269146 TI - Development of genome-wide insertion and deletion markers for maize, based on next-generation sequencing data. AB - BACKGROUND: Insertions and deletions (indels) are the most abundant form of structural variation in all genomes. Indels have been increasingly recognized as an important source of molecular markers due to high-density occurrence, cost effectiveness, and ease of genotyping. Coupled with developments in bioinformatics, next-generation sequencing (NGS) platforms enable the discovery of millions of indel polymorphisms by comparing the whole genome sequences of individuals within a species. RESULTS: A total of 1,973,746 unique indels were identified in 345 maize genomes, with an overall density of 958.79 indels/Mbp, and an average allele number of 2.76, ranging from 2 to 107. There were 264,214 indels with polymorphism information content (PIC) values greater than or equal to 0.5, accounting for 13.39% of overall indels. Of these highly polymorphic indels, we designed primer pairs for 83,481 and 29,403 indels with major allele differences (i.e. the size difference between the most and second most frequent alleles) greater than or equal to 3 and 8 bp, respectively, based on the differing resolution capabilities of gel electrophoresis. The accuracy of our indel markers was experimentally validated, and among 100 indel markers, average accuracy was approximately 90%. In addition, we also validated the polymorphism of the indel markers. Of 100 highly polymorphic indel markers, all had polymorphisms with average PIC values of 0.54. CONCLUSIONS: The maize genome is rich in indel polymorphisms. Intriguingly, the level of polymorphism in genic regions of the maize genome was higher than that in intergenic regions. The polymorphic indel markers developed from this study may enhance the efficiency of genetic research and marker-assisted breeding in maize. PMID- 26269147 TI - Coronary Artery Calcium Score Compared with Cardio-Ankle Vascular Index in the Prediction of Cardiovascular Events in Asymptomatic Patients with Type 2 Diabetes. AB - AIM: Coronary artery calcium (CAC) score has a role in stratifying cardiovascular risk in patients with diabetes. Cardio-ankle vascular index (CAVI) is also a useful method to detect coronary artery calcification. This study compares CAC score with CAVI in the prediction of cardiovascular events in patients with diabetes. METHODS: From August 2006 to June 2008, a total of 626 patients with diabetes who received CAC score assessment with concomitant tests of ankle brachial index and CAVI were included in this study. RESULTS: During 4 years of follow-up, 98 participants developed cardiovascular events. There is an increased incidence of coronary revascularization and total cardiovascular events with higher categories of CAC score (P < 0.05 when CAC score >= 100). The logistic regression analyses revealed pooled odd ratios for coronary revascularization, and total cardiovascular events were 1.25 [95% confidence interval (CI) 1.03- 1.51, P =0.021] and 1.23 (95% CI 1.07-1.42, P = 0.005), respectively, for high versus low CAVI (CAVI >= 9.0 vs CAVI < 9.0). The logistic regression model revealed that a CACscore of >= 1000 rather than a CAVI of >= 9.0 had a higher predictive value for total cardiovascular events. CONCLUSIONS: A CAC score of >= 100 or a CAVI of >= 9.0 predicts future total cardiovascular events in asymptomatic patients with type 2 diabetes. Considering the advantages of CAVI, it can be used as one of the screening tools to reflect coronary atherosclerosis in these patients. PMID- 26269148 TI - Association of Left Ventricular Diastolic Dysfunction with Subclinical Coronary Atherosclerotic Disease Burden Using Coronary Artery Calcium Scoring. AB - AIM: Diastolic dysfunction is a common problem in patients with obesity, hypertension, diabetes, or coronary artery disease. The purpose of this study was to evaluate the association of left ventricular diastolic dysfunction with an abnormal coronary artery calcium score (CAC score). METHODS: This study considered a cohort of patients >= 18 years of age with normal ejection fraction who were admitted to the hospital with chest pain. All patients underwent regadenoson myocardial perfusion stress imaging and had no evidence of ischemia or infarction. Patients then underwent cardiac CT for measurement of CAC score. Patients were excluded if they had prior history of coronary artery disease, ECG findings diagnostic of an acute coronary syndrome, an elevated troponin level, or hemodynamic instability. RESULTS: A total of 114 patients were included and 52 (45.6%) patients had echocardiographic evidence of diastolic dysfunction. Patients with diastolic dysfunction were more likely to have an abnormal calcium score (79.6% vs 20%; OR 15.10, 95% CI 5.70 to 43.85; p < 0.001). In multivariable analysis, the presence of diastolic dysfunction on echocardiogram was significantly associated with an abnormal calcium score (OR 13.82, 95% CI 5.57 to 37.37; p < 0.001) after adjusting for Framingham Risk Score or clinical risk factors (age, gender, diabetes mellitus, dyslipidemia, and obesity; OR 19.06,95% CI 4.66 to 107.97; p < 0.001). CONCLUSIONS: Our study demonstrates that left ventricular diastolic dysfunction is associated with an abnormal CAC score even after adjusting for Framingham Risk Score or clinical risk factors. Patients without known coronary artery disease that present with chest pain and have normal perfusion imaging with evidence of abnormal diastolic function on echocardiogram may warrant more thorough evaluation for coronary atherosclerotic disease with CAC score assessment. PMID- 26269149 TI - The effects of military body armour on the lower back and knee mechanics during box drop and prone to standing tasks. AB - Modern day body armour (BA) has been successful at increasing survivability from previously lethal explosives; however, it has been suggested to reduce warfighter's performance and increase risk of injury. Joint biomechanics have a foremost impact on performance and risk of injury. The immediate and prolonged effects of wearing BA on biomechanics of the lower back and knee during box drop (BD) and prone to standing tasks were investigated. The immediate effects of BA on both tasks were an increase of >=4% (p <= 0.02) in temporal task durations and a decrease of ~1.66 N/kg (p = 0.03) in normalised peak ground reaction force for the BD test. The prolonged duration of walking with BA (i.e. 45 min) was not found to cause more changes in our measures than walking without BA. Quantitative data related to the effects of BA are important for risk assessment and mission design such to reduce the risk of injury without compromising performance. Practitioner Summary: The effects of wearing military body armour (BA) on biomechanics of the lower back and knee were investigated. Though wearing BA was found to affect some biomechanical measures related to performance, the prolonged effects of exposure on our measures were the same whether or not the participants wore BA. PMID- 26269150 TI - Association between metabolic syndrome and multiple lesions of intracranial atherothrombotic stroke: a hospital-based study. AB - BACKGROUND: With the increasing trend of metabolic syndrome (MetS) and atherothrombotic stroke (which can manifest as stroke lesion multiplicity), studies on the association between MetS and the clinical aspects of atherothrombotic stroke are of great interest. The present study aimed to investigate the association between MetS and multiple atherothrombotic strokes in patients with intracranial atherothrombotic stroke. METHODS: A retrospective study based on medical charts was conducted among patients (n = 202: 137 men/65 women) who were symptomatically admitted to the hospital with the first-ever atherothrombotic stroke. For the occurrence of multiple lesions of stroke, odds ratio [OR: 95% confidence interval (CI)] of MetS or its respective components was calculated using logistic regression models. RESULTS: Fifty-one percent of the men and 38% of women with stroke presented multiple regions. MetS was a significant factor that was associated with an increased risk of multiple regions in women [OR 4.3 (95% CI 1.4-13.5)], but not in men. According to the components of MetS, dyslipidemia was a significant factor that was positively associated with multiple regions in both men [OR 2.0 (95% CI 1.1-3.7)] and women [OR 3.2 (95% CI 1.1-9.1)]. CONCLUSION: MetS may be pathophysiologically associated with intracranial atherothrombotic stroke multiplicity in women in particular. Future studies are warranted to confirm the findings. PMID- 26269151 TI - Identifying miRNA/mRNA negative regulation pairs in colorectal cancer. AB - Although considerable progress has been made in the molecular biology of Colorectal cancer (CRC), novel approaches are still required to uncover the detailed molecular mechanism of CRC. We aim to explore the potential negatively regulated miRNA-mRNA pairs and investigate their regulatory roles so as to elaborate the potential roles of the critical proteins in the signaling pathways enriched by the differential target genes of negatively regulated miRNA in CRC. Firstly, the differential miRNA-mRNA pairs were selected, followed by pairs of miRNA and their target genes. The obtained relationships were subjected to do functional enrichment analysis and those enriched in CRC pathways were chose to further construct a protein interaction network. Finally, we analyzed the regulatory roles of these relationships and constructed a regulatory network of negatively regulated miRNA and mRNA relationships. A total of 372 pairs of miRNA mRNA were found and 108 target genes of miRNA were obtained. Three miRNAs including hsa-mir-23b, hsa-mir-365-1 and hsa-mir-365-2 showed significant influence on prognosis of CRC patients. To conclude, the miRNA/mRNA deregulations pairs identified in this study have high potentials to be further applied in diagnosis and treatment of CRC. PMID- 26269152 TI - [Not Available]. PMID- 26269153 TI - Regional changes of placental vascularization in preeclampsia: a review. AB - Preeclampsia is characterized by vascular dysfunction and results in maternal and fetal morbidity and mortality. The placenta plays a critical role in the growth and development of the fetus, and recent studies indicate that placental architecture, oxygen availability, and oxidative stress indices vary across different regions of the placenta. Our earlier studies have reported altered maternal angiogenesis and differential placental gene expression and methylation patterns of angiogenic factors in women with preeclampsia when compared with normotensive women. We have also demonstrated lower maternal and placental neurotrophin (NT) levels in women with preeclampsia. Studies suggest that oxidative stress is associated with proteases like matrix metalloproteinases (MMPs) and growth factors like NTs and angiogenic factors known to be involved in the process of angiogenesis. Recently, we have reported regionwise differential oxidative stress, antioxidant enzyme activity, and NT levels in placenta from normotensive control women and women with preeclampsia. The current review describes the regional changes in the placenta and highlights the role of placental oxidative stress in influencing regional differences in the expression of angiogenic factors, MMPs, and NTs. This review discusses the need for further research on various growth factors and proteins involved in the process of placental development across different regions of the placenta. This would help to understand whether regional differences in these factors affect the growth and development of the fetus. PMID- 26269155 TI - [Epidemiology of prostate cancer in China: an overview and clinical implication]. AB - Prostate cancer is a currently common disease in Chinese male. The incidence is increasing rapidly in urban area and the mortality is high in rural area. According to characteristics of disease stage, advancement in early diagnosis of prostate cancer is the key to improve prostate cancer survival in China. Because of the remarkable disparity in economic and health care across mainland China, a selective prostate cancer screen approach may be a better alternative to spread. Therefore, indepth researches in optimization of prostate specific antigen screen and validation biomarkers of aggressive prostate cancer should be advocated. Furthermore, physicians should take a more active role in population education. PMID- 26269154 TI - Prognostic significance of WNT and hedgehog pathway activation markers in cancer of unknown primary. AB - BACKGROUND: Cancer of unknown primary (CUP) possesses distinct biology and peculiar natural history, in which the roles of the winged and hedgehog signalling pathways are unclear. MATERIALS AND METHODS: We constructed tissue microarrays and studied the immunohistochemical (IHC) expression of beta-catenin, smoothened (SMO) and the transcription factors TCF, LEF, GLI1 in 87 CUP cases for prognostic significance. RESULTS: A low rate of IHC expression of proteins was seen, the cut-off used being any expression in >= 1% of tumour cells. At univariate analysis, only nuclear IHC SMO expression displayed a statistically significant association with favourable outcome [median Overall survival (OS) of 19 months in SMO-positive vs. 12 months in SMO-negative cases, P = 0.01]. An activated Wnt pathway, defined as IHC expression of any of nuclear beta-catenin, TCF and LEF, was significantly associated with favourable progression free survival (median 9 vs. 5 months, P = 0.037) and OS (median 19 vs. 13 months, P = 0.04). This prognostic impact on OS was mainly driven by nuclear expression of TCF and/or LEF (P = 0.03). No prognostic significance of the hedgehog pathway activation status, defined as IHC expression of SMO or nuclear GLI1, could be established. A favourable prognostic impact of the concurrent activation of both pathways was observed. A trend for association of activated Wnt with response to chemotherapy (responders 67% among activated Wnt cases vs. 35% among nonactivated Wnt cases, P = 0.07) was observed in CUP adenocarcinomas. CONCLUSIONS: Activation of the Wnt pathway was a positive prognostic factor in a small CUP series, possibly via enhanced chemosensitivity. Independent validation is warranted. PMID- 26269156 TI - [The focus and prospect of prostate cancer research]. AB - The incidence and mortality of prostate cancer in China are increasing year by year. The review is focused on current hot prospects of prostate cancer. The value of serum prostate specific antigen (PSA) screening is still controversial, and PSA screening in high-risk groups is recommended for early diagnosis of prostate cancer. Prostate biopsy including transrectal approach and perineal approach, and two methods have both advantages and disadvantages. There is significant correlation between testosterone levels and the prognosis of prostate cancer, and the monitoring of testosterone level contributes to the treatment. The main complications of radical resection of prostate cancer is urinary incontinence and erectile dysfunction, three-dimensional laparoscopic and robot assisted laparoscopic techniques have obvious advantages in radical operation. Brachytherapy is another option for radical treatment, with relaxed age limit, low incidence of erectile dysfunction, urinary incontinence and reliable curative effect. The diagnosis and treatment of new technologies include such as MRI dynamic enhancement scan, 18F-fluoroethyl PET/CT, ultrasound contrast technology, prostate cancer immunotherapy, et al. PMID- 26269157 TI - [Analysis of permanent brachytherapy combined with maximal androgen blockade in local intermediated-risk prostate cancer]. AB - OBJECTIVE: To evaluate the outcomes of permanent brachytherapy combined with maximal androgen blockade (MAB) in local intermediated-risk prostate cancer. METHODS: From December 2003 to December 2009, 307 patients of local prostate cancer were treated with brachytherapy, 98 cases of intermediated-risk were followed-up for 5 years and data were recorded, aged from 58 to 84 years, average 74 years. Serum PSA was 0.4-19.0 ug/L, average 11.2 ug/L, clinical TNM stage was T1cN0M0-T2bN0M0. Gleason score 4-7, 6.7 in average. Prostate volume ranged from 14 to 65 ml, average 32.1 ml. All the 98 patients underwent permanent brachytherapy combined with MAB. Biochemical recurrence rate, biochemical-free survival, tumor-specific survival, overall survival, salvage therapy and complications were analyzed. RESULTS: Followed up for 5 years, 19 cases had biochemical recurrence, median recurrence period: 36 months. One patient died of prostate cancer 45 months after brachytherapy of all 7 patients died in 5 years. Five-years biochemical-free recurrence rate: 80.6%, overall survival: 92.9%, tumor-specific survival: 98.9%, biochemical-free survival: 79.3%. Low-urinary tract and rectal irritation symptoms occurred in 75 cases(76.5%). Urinary retention occurred in 7 cases (7.1%) with catheterization duration less than 1 week, no surgical operation were performed. Seeds immigration to lung in 2 cases. No serious complications occurred. CONCLUSION: In local intermediated-risk prostate cancer patients, permanent brachytherapy combined with short-term MAB can be an effective treatment with few complications. PMID- 26269158 TI - [Analysis of biochemical recurrence following radical prostatectomy]. AB - OBJECTIVE: To analyze the risk factors to impact biochemical recurrence after radical prostatectomy. METHODS: A total of 1 090 patients who received radical prostatectomy from May 2002 to December 2013 in Department of Urology of Fudan University Shanghai Cancer Center were recruited. The average age of the patients was 67.9 years (ranged from 41 to 84 years) and the average preoperative prostate specific antigen (PSA) level was 32.7 (ranged from 3.2 to 256.3) ug/L. The distribution of patients with respect to clinical stage was: 20.09% (219/1 090) had T1, 50.09% (546/1 090) had T2 and 29.82% (325/1 090) had T3. The biochemical free-survival curve was drawn by Kaplan-Meier method and the univariate and multivariate Cox regression models were used to evaluate the clinical and pathological variables for the development of biochemical recurrence. RESULTS: Of all the 1 090 patients, the biochemical recurrence free survival was 95.99%, 81.90% and 70.89% at 1, 3 and 5 years. PSA level at diagnosis (P=0.000), neo adjuvant hormonal therapy (P=0.001), pre-operative Gleason score (P=0.000), clinical stage (P=0.010), surgical margin status (P=0.028), post-operative Gleason score (P=0.000), pathological stages (P=0.000) and pelvic lymph-node metastasis (P=0.000) were associated with biochemical recurrence in the univariate analysis. However, in the multivariate analysis, only PSA level at diagnosis (P=0.000), pre-operative Gleason score (P=0.020), pathological stages (P=0.014) and pelvic lymph-node metastasis (P=0.017) were independent prognostic factors. CONCLUSION: For the patients who received radical prostatectomy, PSA level at diagnosis, pre-operative Gleason score, pathological stages and pelvic lymph-node metastasis status are independent prognostic factors for biochemical recurrence. PMID- 26269159 TI - [Clinical analysis of transperineal prostate biopsy in patients age <= 50 years]. AB - OBJECTIVE: To assess the clinical features of transperineal prostate biopsy in patients age <=50 years. METHODS: The clinical data of 124 patients <= 50 years old were retrieved retrospectively in Peking Union Medical College Hospital between January 2005 and September 2014. The age of patients were 14 to 50 years (mean age 43.6 years), and their prostatic specific antigen(PSA) levels were fluctuated in a range of 0.01 to 579.00 ug/L (mean 15.5 ug/L). Twenty patients were abnormal in digital rectal examination (DRE). All the patients were underwent transperineal prostate biopsy using an 11-region template. RESULTS: Prostate cancer was detected in 14 of 124 patients (11.3%). The prostate cancer detection rates in groups with PSA 0-4.0, >4.0-10.0, >10.0-20.0, >20.0-50.0, and >50.0 ug/L were 0, 6.2% (4/65), 13.3% (4/30), 1/5, and 5/5, respectively. Non adenocarcinoma prostate malignancy (NAPM) was detected in 7 of 124 patients (5.6%), and their PSA levels were fluctuated in a range of 0 to 4.0 ug/L. Four patients were abnormal in DRE and 5 patients were abnormal in radiological examination. CONCLUSION: The positive rate of transperineal prostate biopsy in patients age<=50 years is low, and rigorous screening before prostate biopsy is necessary. The men with DRE or radiological abnormalities but normal PSA should be wary of NAPM. PMID- 26269160 TI - [Clinical predictors of cytomegalovirus infection after liver transplantation]. AB - OBJECTIVE: To investigate the clinical predictors of cytomegalovirus (CMV) infection after liver transplantation. METHODS: The clinical data of 182 patients (146 male and 36 female with a mean age of (50 +/- 7) years) receiving liver transplantation in Beijing Chaoyang Hospital between January 2004 and December 2008 were retrospectively analyzed.All patients were divided into two groups, namely the CMV infection group (n=24) and the control group (n=158). Logistic regression was used to identify the predictive factors of postoperative CMV infection. RESULTS: According to univariate analysis results, the factors for CMV infection were acute liver failure (P=0.032), MELD score >= 30 (P=0.001), liver retransplantation (P=0.002), acute rejection (P=0.000) and delayed graft function (P=0.022). According to multi-analysis results, MELD score >= 30 (P=0.037, 95%CI:1.194-271.461) and acute rejection (P=0.033, 95%CI:1.179-51.863) were proved to be independent predictors by multivariate analysis. CONCLUSION: The study indicates that MELD score >= 30 and acute rejection are the independent predictors of CMV infection. PMID- 26269161 TI - [Clinical pathological features and prognosis analysis of gastrointestinal stromal tumor: a series of 558 cases]. AB - OBJECTIVE: To investigate and analysis the clinical and pathological characteristic of gastrointestinal stromal tumor (GIST) patients, and to clarify the factors that effect on prognosis. METHODS: The clinical and pathological features and follow-up of GIST patients who received surgery in Peking Union Medical College Hospital from May 2002 to December 2013 were analyzed retrospectively. The prognosis was evaluated by univariate and multivariate analysis. Kaplan-Meier unvariate analysis and Log-rank test were used to compare the survival rates. Multivariate factors for survival were analyzed by Cox proportional hazards regression model. RESULTS: A total of 558 GIST patients were collected, including 284 males and 272 females. The high incidence was in the elderly and age of 50 to 70 years. Most of the primary tumors are located in stomach (303 cases), followed by the small intestine (118 cases). Surgical procedures included R0 resection in 517 cases, R1 resection in 4 cases, R2 or palliative resection in 37 cases. The recurrence risk was very low in 102 cases, low in 156 cases, moderate in 67 cases and high in 233 cases. Of all the patients, 495 cases completed the follow-up, the follow-up rate was 88.7%. Five year survival rate was 87.4%. Patients who took targeted therapy with moderate and high risk of recurrence had a better prognosis compared with not taking the drug. Univariate analysis revealed that the factors impacting the prognosis were age, tumor size, tumor site and mitotic count. Multivariate analysis showed that tumor size (P=0.01, RR=1.562, 95% CI: 1.452 to 15.664), location (P=0.01, RR=1.552, 95% CI:1.324 to 12.225), mitotic figures (P<0.01, RR=1.415, 95% CI: 2.126 to 7.968) and tumor rupture (P=0.01, RR=1.578, 95% CI: 1.543 to 15.892) were independent prognostic factors. CONCLUSION: R0 resection combined with targeted therapy is the best treatment of GIST. Tumor size, location, mitosis count and tumor rupture are independent prognostic factors of GIST patients. PMID- 26269162 TI - [Accuracy of MRI for estimating residual tumor size after neoadjuvant chemotherapy in breast cancer with three-dimensional reconstruction technique]. AB - OBJECTIVE: To evaluate the accuracy of MRI for estimating residual tumor size after neoadjuvant chemotherapy (NAC) with three-dimensional (3D) reconstruction technique. METHODS: This was a prospective study. The data of 61 patients with pathologically proven solitary invasive ductal carcinoma (IIA-IIIC) who had received 6 to 8 cycles of NAC from July 2010 to August 2013 was analyzed. All the patients were female, aging from 31 to 70 years with a median of 49 years. Breast specimen after surgery was prepared with part-mount sub-serial section, and residual tumors were microscopically outlined, scanned and registered by Photoshop software. The 3D model of pathological and MRI residual tumors was reconstructed with 3D-DOCTOR software. The longest diameter, maximum cross section area and volume of the residual tumors determined using 3D MRI were compared with 3D pathological findings, and the associations between MRI and pathology were analyzed by Spearman rank correlation and Bland-Altman analysis. RESULTS: The longest diameter, maximum cross-section area and volume of the residual tumors after NAC measured by MRI and pathology was highly correlated (r=0.942, 0.941, 0.903, all P=0.00). MRI appears to underestimate pathology in the longest diameter, maximum cross-section area, but slightly overestimate in volume, and two methods had a good consistence (MD=0.3 cm, 95% CI: -1.43 to 1.9 cm; MD=1.39 cm2, 95% CI: -9.55 to 12.34 cm2; MD=-0.433 cm3, 95% CI: -7.065 to 6.199 cm3). CONCLUSION: 3D MRI reconstruction after NAC could accurately detects the residual tumors after neoadjuvant chemotherapy, and contribute to select patients who received breast conserving therapy after NAC with tumor downstaging. PMID- 26269163 TI - [The correlation between shifting of the patient's gravity center position and the degree of recovering joint function after total knee arthroplasty]. AB - OBJECTIVE: To study the correlation between the shifting degree of the gravity center position (GCP) and recovering degree of the knee's function of the patients after total knee arthroplasty (TKA) at the same time point. METHODS: One hundred and seventy-six patients who underwent single TKA between June 2012 and December 2013 were measured GCP by corresponding instrument prospectively. Ninety two patients underwent right knee arthroplasty (25 male and 67 female), eighty four patients underwent left knee arthroplasty (21 male and 63 female). They were evaluated by Hospital For Special Surgery (HSS) scores pre-operatively, 6-month and 1-year post-operatively, and were measured GCP simultaneously. Pearson's correlation analysis were conducted between shifting degree of GCP and changing degree of HSS score when be compared with pre-operatively. RESULTS: All the patient's HSS score had significantly improved at 6-month and 1-year after surgery than pre-operatively (right knee group: t=-42.82 and -62.46, all P=0.00; left knee group: t=-43.10 and -62.82, all P=0.00). HSS scores had been improved from 51.6 +/- 4.2 to 76.6 +/- 3.6 and 86.5 +/- 3.1 in right knee patients, and improved from 52.2 +/- 4.5 to 76.0 +/- 3.8, 86.6 +/- 2.7 in left knee patients at 6-month and 1-year after surgery. There was a correlation between shifting degree of GCP and changing degree of HSS score 6-month and 1-year after surgery (r=0.424 and 0.139). CONCLUSION: As recovering of the joint function, the weight on operated limb could be increased, thus the GCP moves from its initial position to the operative side after TKA. While, the shifting degree of GCP can be a reflection of recovering of the joint function in some extent. PMID- 26269164 TI - [The correlation analysis of balloon volume and bone cement volume in percutaneous kyphoplasty]. AB - OBJECTIVE: To analyze the percutaneous kyphoplasty (PKP) data statistically to predict the bone cement volume (CV). METHODS: Retrospective analysis of 93 patients with 154 vertebrae of osteoporotic vertebra compressed fracture, who received PKP from January 2012 to December 2013 in Beijing Tian Tan Hospital, Capital Medical University. All procedures were bilateral and non-high-pressure polymethyl methacrylate injection. The balloon volume (BV), balloon peak pressure (Pmax), CV and the ratio of Pmax to BV (P/BV) were documented. The data was analyzed by correlation analysis and linear regression analysis to reveal the correlation between BV and CV. RESULTS: Seven vertebrae had bone cement leakage, no intraspinal leakage, no neuro-deficit. Visual analogue scale was 0-2 of all patients on 3 d postoperation. The data of 147 vertebrae without leakage: BV was 2.1-6.3 ml, Pmax was 130-359 psi, CV was 2.8-8.5 ml, and the ratio of Pmax to BV (P/BV) was 25-263 psi/ml. The data analysis showed there was no high correlation between BV and CV as one group (R<0.75). However if divided the data into three groups by the value of P/BV, group A (P/BV<100), group B (100<=P/BV<200), group C (P/BV>=200), there was high correlation and linear relationship between BV and CV in each group (R>0.75, P<0.01). CV was 0.9-1.1 times of BV in group A; CV was 1.4 1.6 times of BV in group B; and CV was 2.0-2.2 times of BV in group C. CONCLUSION: CV is predictable by the BV and the ratio of Pmax to BV. It can reduce the rate of the leakage, and also can prevent the unsatisfactory results by insufficient bone cement volume. PMID- 26269165 TI - [Paraspinal muscle approach with winglike working channel in the treatment of thoracic and lumbar spine fracture]. AB - OBJECTIVE: To evaluate the clinical and radiological efficacy of paraspinal muscle approach with winglike working channel in the treatment of thoracic and lumbar spine fracture. METHODS: From October 2010 to August 2012, a total of 51 patients with thoracic and lumbar spine fractures without neurological symptoms were enrolled in the study, including 32 males and 19 females. All patients were divided into two groups: 26 patients were treated through posterior paraspinal muscle approach with winglike working channel, and 25 patients were treated through traditional posterior approach. In all patients, the interval between injury and operation was less than two weeks; the vertebral canal blocked area was less than 1/3 in sagittal diameter; the compression of the fractured vertebra height was less than 2/3. And the patients with pathological fracture and severe osteoporosis were excluded. The perioperative index including operative blood loss, draining loss, operative time, postoperative bed time were recorded. The clinical results were evaluated by visual analogue scale (VAS) for back pain preoperatively, at 3 days, 3 months, the last follow-up postoperatively and modified Macnab criteria at the last follow-up. The radiological results were evaluated by sagittal Cobb angle and the anterior height of the fractured vertebra. The data of two groups were compared statistically with paired and independent t test, chi2 test, Mann-Whitney U test and Wilcoxon test. RESULTS: All patients were followed up with average of 16.6 months. In the two groups, the operative blood loss was respectively (91.5 +/- 36.6) ml and (209.2 +/- 38.3) ml (t=-11.216, P=0.000), draining loss was (13.7+/-4.4) ml and (162.3 +/- 56.6) ml (t=-13.352, P=0.000), postoperative bed time was (87.3 +/- 11.5) hours and (118.4 +/- 20.4) hours (t=-6.727, P=0.000), VAS for back pain at 3 days postoperatively was 5.5 +/- 1.0 and 6.4 +/- 0.8 (t=-3.304, P=0.002), also VAS at the last follow up was 1.0 (1.0) and 2.0 (1.0) (U=191.0, P=0.008). Data above showed significant differences between the two groups.No significant differences were found in operative time, (109.0 +/- 29.7) min vs. (119.2 +/- 26.8) min (t=-1.283, P=0.206), and modified Macnab criteria (chi2=0.513, P=0.774) between the two groups. The anterior height of the fractured vertebra preoperatively, at 1 week and the last follow-up postoperatively of the two groups were respectively (57.2 +/- 11.8)% and (55.2 +/- 10.9)% (t=0.685, P=0.496), (95.2 +/- 8.3)% and (95.3 +/- 5.8%) (t=-0.068, P=0.946), (92.9 +/- 6.7)% and (92.1 +/- 5.6)% (t=0.505, P=0.615). The sagittal Cobb angles preoperatively, at 1 week and the last follow up postoperatively of the two groups were respectively 21.0 degrees (12.5 degrees ) and 23.0 degrees (12.0 degrees ) (U=316.0, P=0.544), 3.0 degrees (5.5 degrees ) and 4.0 degrees (4.5 degrees ) (U=342.5, P=0.893), 4.0 degrees (5.5 degrees ) and 6.0 degrees (6.0 degrees ) (U=328.5, P=0.701). There were no significant differences of these radiological results between the two groups in the same time point. CONCLUSION: The paraspinal muscle approach with winglike working channel in the treatment of thoracic and lumbar spine fracture is an efficient surgical option which can acquire satisfactory clinical and radiological results. PMID- 26269166 TI - [Three-dimensional print of aortic aneurysm models aid preoperative planning in complicated endovascular repair procedure]. AB - OBJECTIVE: To attempt to produce highly accurate three-dimensional (3D) printed models of aortic aneurysm models aid complicated preoperative planning in endovascular repair procedures. METHODS: From October 2012 to May 2014, six patients with complicated aortic aneurysms (one aortic arch aneurysms, one thoracoabdominal aortic aneurysms and four juxtarenal abdominal aortic aneurysms) accepted preoperative contrast-enhanced CT angiography (CTA) scans for procedural planning, 4 male and 2 female, average age 64 years (range 52 to 73 years). All the CTA data were processed with FitMe 3D image processing software to get the modified 3D reconstruction pictures and computer language that can be identified by the 3D printer. With the fused deposition modeling technology, the highly accurate models were got to make preoperative endovascular planning. RESULTS: All the patients' models were printed before operations. By the guidance of models, the endovascular procedure plans were drawn up. Three patients were performed extracorporeal simulating operations with the models and four patients' endovascular operations were guided by the models during the intraoperative time. The procedure technique success rate was 100%. No serious complications and patients dead during the perioperative period. CONCLUSION: The technology of 3D printed highly accurate models of aortic aneurysm models is feasible and can help to make preoperative endovascular planning for improving the safety of complicated procedures. PMID- 26269167 TI - [Trends in lower extremity peripheral arterial disease treatments and prognosis: a 10 years' experience in single center]. AB - OBJECTIVE: To analyze the trends in treatments of lower extremity peripheral arterial disease and their prognosis in the recent 10 years. METHODS: Clinical data of inpatients with lower extremity peripheral arterial disease who received surgical treatments in Xuanwu Hospital from January 2002 to December 2011 were analyzed retrospectively. Patients were stratified into two groups (group 1: from 2002 to 2006, group 2: from 2007 to 2011). The demographics, risk factors, clinical presentation, lesion anatomy, therapies, limb salvage and survival were observed. chi(2) test, Fisher exact test, and t test were used to compare the data between the two groups. RESULTS: From 2002 to 2006, 170 limbs (47.49%) underwent conventional bypass surgery, 72 limbs (20.11%) underwent endovascular interventions and the rest 116 limbs (32.40%) received stem cell treatment. While from 2007 to 2011, the percentages were 18.49%, 68.73%, 8.27%, respectively. Furthermore, gene-based drug appeared, 67 limbs (4.51%) underwent the new treatment. Former group had decreased limb salvage rates compared with latter group (87.15% vs. 93.41%, chi(2)=15.71, P=0.000). However, survival rates did not differ from the two groups (84.67% vs. 84.31%, chi(2)=0.02, P=0.880). CONCLUSION: With the appearance of new medical instruments and operating methods, the percentage of the patients with lower extremity peripheral arterial disease receive endovascular interventions increases, with a improved limb salvage rates. PMID- 26269168 TI - [Experimental study about the impact of the regeneration of interstitial cell of Cajal on gastric emptying in rats undergoing Roux-en-Y gastrojejunostomy]. AB - OBJECTIVE: To investigate the impact of the regeneration of interstitial cell of Cajal (ICC) on the conduction of slow wave and gastric emptying in rats undergoing Roux-en-Y gastrojejunostomy. METHODS: Twenty male SD rats were randomly divided into experimental group and control group. The experimental group consisted of ten rats undergoing Roux-en-Y gastrojejunostomy. The control group only underwent pyloric transection and anastomosis. Gastric scintigraphy was performed in the two groups respectively to measure the half time of gastric emptying (t1/2) at sixteen weeks after the surgical manipulations, and then the myoelectrical activities near the gastrojejunal anastomosis were recorded. The study also observed the regeneration of ICC by the electron microscopy. The data of the 2 groups was compared by t test. RESULTS: In the sixteenth postoperative week, the t1/2 was (23.5 +/- 4.5) minutes for rats in the Roux-en-Y group and (10.2 +/- 2.3) minutes for those in the control group, indicating delayed gastric emptying in the Roux-en-Y group (t=7.978, P=0.000), accompanied with the abnormal myoelectrical activities near the gastrojejunal anastomosis. The morphological detection showed that ICC near the gastrojejunal anastomosis regenerated and reconstructed their network in the rats of the experimental group. CONCLUSION: The abnormal myoelectrical activities near the gastrojejunal anastomosis, basing on the regeneration and reconstruction of ICC, may make a significant delay on the gastric emptying. PMID- 26269169 TI - [New progress in prostate cancer biomarker research]. AB - Prostate cancer is one of the major problems of men's health. It has more obvious cancer heterogeneity, affecting the diagnosis, treatment and prognosis monitoring when comparing with other cancer. Thus, cancer related biomarkers are urgently needed to guide biopsy, treatment selection and follow-up. In the aspect of diagnosis, though the emerging of prostate specific antigen can raise the rate of diagnosis to some extent, it brings more unnecessary biopsies because of its low specificity. Cancer related long non-coding RNAs, single nucleotide polymorphism and fusion genes are proved to increase the diagnostic efficiency through high throughput sequencing techniques. In the aspect of molecular classification, traditional Gleason score can discriminate different risk level of the cancer, but it is limited by the technicians. It is reported that copy number variations from DNA level and small RNAs, long non-coding RNAs from RNA level are related with the progress of cancer, indicating the potential role in cancer molecular classification. Although we are still on the way of the initial stage in exploring prostate cancer biomarkers, more useful and promising biomarkers will be found by high-throughput sequencing and molecular biotechniques. PMID- 26269170 TI - Inhibition of Histone Deacetylase Activity Aggravates Coxsackievirus B3-Induced Myocarditis by Promoting Viral Replication and Myocardial Apoptosis. AB - Viral myocarditis, which is most prevalently caused by coxsackievirus B3 (CVB3), is a serious clinical condition characterized by excessive myocardial inflammation. Recent studies suggest that regulation of protein acetylation levels by inhibiting histone deacetylase (HDAC) activity modulates inflammatory response and shows promise as a therapy for several inflammatory diseases. However, the role of HDAC activity in viral myocarditis is still not fully understood. Here, we aim to investigate the role of HDAC activity in viral myocarditis and its underlying mechanism. CVB3-infected BALB/c mice were treated with the HDAC inhibitor (HDACI) suberoylanilide hydroxamic acid (SAHA) or trichostatin A (TSA). We found inhibition of HDAC activity aggravated rather than ameliorated the severity of CVB3-induced myocarditis, which was contrary to our expectations. The aggravated myocarditis by HDACI treatment seemed not to be caused by an elevated inflammatory response but by the increased CVB3 replication. Further, it was revealed that the increased CVB3 replication was closely associated with the HDACI-enhanced autophagosome formation. Inhibition of autophagosome formation by wortmannin or ATG5 short hairpin RNA dramatically suppressed the HDACI-increased CVB3 replication. The increased viral replication subsequently elevated CVB3-induced myocardial apoptosis. Conversely, inhibition of CVB3 replication and ensuing myocardial apoptosis by the antiviral drug ribavirin significantly reversed the HDACI-aggravated viral myocarditis. In conclusion, we elucidate that the inhibition of HDAC activity increases CVB3 replication and ensuing myocardial apoptosis, resulting in aggravated viral myocarditis. Possible adverse consequences of administering HDACI should be considered in patients infected (or coinfected) with CVB3. IMPORTANCE: Viral myocarditis, which is most prevalently caused by CVB3, is characterized by excessive myocardial inflammation. Inhibition of HDAC activity was originally identified as a powerful anti-cancer therapeutic strategy and was recently found to be implicated in the regulation of inflammatory response. HDACI has been demonstrated to be efficacious in animal models of several inflammatory diseases. Thus, we hypothesize that inhibition of HDAC activity also protects against CVB3 induced viral myocarditis. Surprisingly, we found inhibition of HDAC activity enhanced myocardial autophagosome formation, which led to the elevated CVB3 viral replication and ensuing increased myocardial apoptosis. Viral myocarditis was eventually aggravated rather than ameliorated by HDAC inhibition. In conclusion, we elucidate the role of HDAC activity in viral myocarditis. Moreover, given the importance of HDACI in preclinical and clinical treatments, the possible unfavorable effect of HDACI should be carefully evaluated in patients infected with viruses, including CVB3. PMID- 26269171 TI - Viral Source-Independent High Susceptibility of Dendritic Cells to Human T-Cell Leukemia Virus Type 1 Infection Compared to That of T Lymphocytes. AB - Human T-cell leukemia virus type 1 (HTLV-1)-infected CD4(+) T cells and dendritic cells (DCs) are present in peripheral blood from HTLV-1 carriers. While T-cell infection requires cell-cell contact, DCs might be infected with cell-free virus, at least in vitro. However, a thorough comparison of the susceptibilities of the two cell types to HTLV-1 infection using cell-associated and cell-free viral sources has not been performed. We first determined that human primary monocyte derived dendritic cells (MDDCs) were more susceptible to HTLV-1 infection than their autologous lymphocyte counterparts after contact with chronically infected cells. Next, a comparison of infection efficiency using nonconcentrated or concentrated supernatants from infected cells as well as purified viral biofilm was performed. Integrated provirus was found after exposure of MDDCs or primary lymphocytes to viral biofilm but not to a viral supernatant. Using a large series of primary cell samples (n = 21), we demonstrated a higher proviral load in MDDCs exposed to viral biofilm than in lymphocytes. This higher susceptibility is correlated to a higher expression of neuropilin-1 on MDDCs than on autologous activated T lymphocytes. Moreover, we show that MDDCs infected with viral biofilm can transmit the virus to lymphocytes. In conclusion, MDDCs are more susceptible to HTLV-1 infection than autologous lymphocytes in vitro, supporting a model in which DC infection might represent an important step during primo-infection in vivo. IMPORTANCE: HTLV-1 is able to infect several cell types, but viral DNA is mainly found in T lymphocytes in vivo. This supports a model in which T lymphocytes are the main target of infection. However, during the primo-infection of new individuals, incoming viruses might first encounter dendritic cells (DCs), the specialized immune cells responsible for the antiviral response of the host. HTLV-1 cell-free purified viruses can infect dendritic cells in vitro, while T cell infection is restricted to cell-to-cell transmission. In order to understand the sequence of HTLV-1 dissemination, we undertook a direct comparison of the susceptibilities of the two cell types using cell-associated and cell-free viral sources. We report here that MDDCs are more susceptible to HTLV-1 infection than autologous lymphocytes in vitro and are able to efficiently transmit the virus to lymphocytes. Our results suggest that DCs may represent a true viral reservoir, as the first cell type to be infected in vivo. PMID- 26269173 TI - A Molecular Staple: D-Loops in the I Domain of Bacteriophage P22 Coat Protein Make Important Intercapsomer Contacts Required for Procapsid Assembly. AB - Bacteriophage P22, a double-stranded DNA (dsDNA) virus, has a nonconserved 124 amino-acid accessory domain inserted into its coat protein, which has the canonical HK97 protein fold. This I domain is involved in virus capsid size determination and stability, as well as protein folding. The nuclear magnetic resonance (NMR) solution structure of the I domain revealed the presence of a D loop, which was hypothesized to make important intersubunit contacts between coat proteins in adjacent capsomers. Here we show that amino acid substitutions of residues near the tip of the D-loop result in aberrant assembly products, including tubes and broken particles, highlighting the significance of the D loops in proper procapsid assembly. Using disulfide cross-linking, we showed that the tips of the D-loops are positioned directly across from each other both in the procapsid and the mature virion, suggesting their importance in both states. Our results indicate that D-loop interactions act as "molecular staples" at the icosahedral 2-fold symmetry axis and significantly contribute to stabilizing the P22 capsid for DNA packaging. IMPORTANCE: Many dsDNA viruses have morphogenic pathways utilizing an intermediate capsid, known as a procapsid. These procapsids are assembled from a coat protein having the HK97 fold in a reaction driven by scaffolding proteins or delta domains. Maturation of the capsid occurs during DNA packaging. Bacteriophage HK97 uniquely stabilizes its capsid during maturation by intercapsomer cross-linking, but most virus capsids are stabilized by alternate means. Here we show that the I domain that is inserted into the coat protein of bacteriophage P22 is important in the process of proper procapsid assembly. Specifically, the I domain allows for stabilizing interactions across the capsid 2-fold axis of symmetry via a D-loop. When amino acid residues at the tip of the D-loop are mutated, aberrant assembly products, including tubes, are formed instead of procapsids, consequently phage production is affected, indicating the importance of stabilizing interactions during the assembly and maturation reactions. PMID- 26269172 TI - Nef Is Dispensable for Resistance of Simian Immunodeficiency Virus-Infected Macrophages to CD8+ T Cell Killing. AB - Simian immunodeficiency virus (SIV)-specific CD8(+) T cells kill SIV-infected CD4(+) T cells in an major histocompatibility complex class I (MHC-I)-dependent manner. However, they are reportedly less efficient at killing SIV-infected macrophages. Since the viral accessory protein Nef has been shown to downregulate MHC-I molecules and enhance cytotoxic T lymphocyte (CTL) evasion in human immunodeficiency virus type 1 (HIV-1)-infected CD4(+) T cells, we examined whether Nef played a role in protecting SIV-infected macrophages from killing by SIV-specific CD8(+) T cells. To explore the role of Nef in CD8(+) T cell evasion, we compared the ability of freshly sorted SIV-specific CD8(+) T cells to readily suppress viral replication or eliminate CD4(+) T cells or monocyte-derived macrophages infected with SIV variants containing wild-type (WT) or mutated nef genes. As expected, SIV-specific CD8(+) T cells suppressed viral replication and eliminated the majority of SIV-infected CD4(+) T cells, and this killing was enhanced in CD4(+) T cells infected with the nef variants. However, macrophages infected with nef variants that disrupt MHC-I downregulation did not promote rapid killing by freshly isolated CD8(+) T cells. These results suggest that mechanisms other than Nef-mediated MHC-I downregulation govern the resistance of SIV-infected macrophages to CD8(+) T cell-mediated killing. This study has implications for viral persistence and suggests that macrophages may afford primate lentiviruses some degree of protection from immune surveillance. IMPORTANCE: Myeloid cells are permissive for HIV/SIV replication in vitro and may contribute to viral persistence in vivo. While many studies have been geared to understanding how CD8(+) T cells control viral replication in CD4(+) T cells, the role of these cells in controlling viral replication in macrophages is less clear. Primary, unstimulated CD8(+) T cells insignificantly suppress viral replication or eliminate SIV-infected macrophages. Since the viral Nef protein downregulates MHC-I and provides infected cells some degree of protection from CD8(+) T cell-mediated effector functions, we evaluated whether Nef may be contributing to the resistance of macrophages to CD8(+) T cell suppression. Our results suggest that Nef is not involved in protecting infected macrophages from CD8(+) T cell killing and suggest that other mechanisms are involved in macrophage evasion from CD8 surveillance. PMID- 26269174 TI - Actin-Modulating Protein Cofilin Is Involved in the Formation of Measles Virus Ribonucleoprotein Complex at the Perinuclear Region. AB - In measles virus (MV)-infected cells, the ribonucleoprotein (RNP) complex, comprised of the viral genome and the nucleocapsid (N) protein, phosphoprotein (P protein), and large protein, assembles at the perinuclear region and synthesizes viral RNAs. The cellular proteins involved in the formation of the RNP complex are largely unknown. In this report, we show that cofilin, an actin-modulating host protein, interacts with the MV N protein and aids in the formation of the RNP complex. Knockdown of cofilin using the short hairpin RNA reduces the formation of the RNP complex after MV infection and that of the RNP complex-like structure after plasmid-mediated expression of MV N and P proteins. A lower level of formation of the RNP complex results in the reduction of viral RNA synthesis. Cofilin phosphorylation on the serine residue at position 3, an enzymatically inactive form, is increased after MV infection and the phosphorylated form of cofilin is preferentially included in the complex. These results indicate that cofilin plays an important role in MV replication by increasing formation of the RNP complex and viral RNA synthesis. IMPORTANCE: Many RNA viruses induce within infected cells the structure called the ribonucleoprotein (RNP) complex in which viral RNA synthesis occurs. It is comprised of the viral genome and proteins that include the viral RNA polymerase. The cellular proteins involved in the formation of the RNP complex are largely unknown. In this report, we show that cofilin, an actin-modulating host protein, binds to the measles virus (MV) nucleocapsid protein and plays an important role in the formation of the MV RNP complex and MV RNA synthesis. The level of the phosphorylated form of cofilin, enzymatically inactive, is increased after MV infection, and the phosphorylated form is preferentially associated with the RNP complex. Our findings determined with cofilin will help us better understand the mechanism by which the RNP complex is formed in virus-infected cells and develop new antiviral drugs targeting the RNP complex. PMID- 26269175 TI - Envelope Glycoprotein Internalization Protects Human and Simian Immunodeficiency Virus-Infected Cells from Antibody-Dependent Cell-Mediated Cytotoxicity. AB - The cytoplasmic tails of human and simian immunodeficiency virus (HIV and SIV, respectively) envelope glycoproteins contain a highly conserved, membrane proximal endocytosis motif that prevents the accumulation of Env on the surface of infected cells prior to virus assembly. Using an assay designed to measure the killing of virus-infected cells by antibody-dependent cell-mediated cytotoxicity (ADCC), we show that substitutions in this motif increase the susceptibility of HIV-1- and SIV-infected cells to ADCC in a manner that directly correlates with elevated Env levels on the surface of virus-infected cells. In the case of HIV-1, this effect is additive with a deletion in vpu recently shown to enhance the susceptibility of HIV-1-infected cells to ADCC as a result of tetherin-mediated retention of budding virions on the cell surface. These results reveal a previously unappreciated role for the membrane-proximal endocytosis motif of gp41 in protecting HIV-1- and SIV-infected cells from antibody responses by regulating the amount of Env present on the cell surface. IMPORTANCE: This study reveals an unappreciated role for the membrane-proximal endocytosis motif of gp41 in protecting HIV-1- and SIV-infected cells from elimination by Env-specific antibodies. Thus, strategies designed to interfere with this mechanism of Env internalization may improve the efficacy of antibody-based vaccines and antiretroviral therapies designed to enhance the immunological control of HIV-1 replication in chronically infected individuals. PMID- 26269177 TI - Improvement of HIV-1 and Human T Cell Lymphotropic Virus Type 1 Replication Dependent Vectors via Optimization of Reporter Gene Reconstitution and Modification with Intronic Short Hairpin RNA. AB - Cell-to-cell transmission is an efficient mechanism to disseminate human immunodeficiency virus type 1 (HIV-1) and human T cell lymphotropic virus type 1 (HTLV-1). However, it has been challenging to quantify the level of cell-to-cell transmission because the virus-producing cells cannot be easily distinguished from infected target cells. We have previously described replication-dependent vectors that can quantify infection events in cocultured cells. These vectors contain an antisense-oriented promoter and reporter gene interrupted by a sense oriented intron from the human gamma-globin gene. This strategy prevents expression of the reporter gene in the transfected cells but permits its expression in target cells after infection. However, the gamma-globin intron is not efficiently removed by splicing in the aforementioned vectors, thereby reducing the level of reporter gene expression after transduction into target cells. Here, we used two approaches to improve the replication-dependent vectors. First, we improved the splicing events that remove the gamma-globin intron by optimizing the intron insertion site within the reporter gene. Second, we improved the packaging of the spliced RNA without the gamma-globin intron by targeting the intron-containing RNA via microRNA 30 (miR30)-based short hairpin RNAs. Using two optimized fluorescent reporter vectors and flow cytometry, we determined that multiply HIV-1-infected cells were generated at a higher frequency in coculture than in cell-free infection; furthermore, this increase was dependent upon viruses bearing HIV-1 Env. Compared with previously described vectors, these improved vectors can quantify the infection in lymphocytes and in primary cells with a higher sensitivity and allow the detection and quantitation of multiply infected cells, providing better tools to study retroviral cell mediated infection. IMPORTANCE: The human-pathogenic retroviruses HTLV-1 and HIV 1 can be transmitted more efficiently in vivo via direct contact of infected cells with healthy target cells than through cell-free virion-mediated infection. Despite its importance, cell-to-cell transmission has been difficult to quantify because the previously infected cells and the newly infected cells are mixed together in the same culture. In the current study, we generated vectors that are significantly improved over the previously described replication-dependent vectors. As a result, these improved vectors can efficiently detect and quantify cell-to-cell transmission or new infection events in cells in mixed culture. These luciferase- or fluorescence protein-based reporter vectors can be used to quantify and study HIV-1 or HTLV-1 cell-mediated infection in a simple one-step transfection/infection assay. PMID- 26269176 TI - Structures of Coxsackievirus A16 Capsids with Native Antigenicity: Implications for Particle Expansion, Receptor Binding, and Immunogenicity. AB - Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the primary causes of the epidemics of hand-foot-and-mouth disease (HFMD) that affect more than a million children in China each year and lead to hundreds of deaths. Although there has been progress with vaccines for EV71, the development of a CVA16 vaccine has proved more challenging, and the EV71 vaccine does not give useful cross-protection, despite the capsid proteins of the two viruses sharing about 80% sequence identity. The structural details of the expanded forms of the capsids, which possess nonnative antigenicity, are now well understood, but high resolution information for the native antigenic form of CVA16 has been missing. Here, we remedy this with high resolution X-ray structures of both mature and natural empty CVA16 particles and also of empty recombinant viruslike particles of CVA16 produced in insect cells, a potential vaccine antigen. All three structures are unexpanded native particles and antigenically identical. The recombinant particles have recruited a lipid moiety to stabilize the native antigenic state that is different from the one used in a natural virus infection. As expected, the mature CVA16 virus is similar to EV71; however, structural and immunogenic comparisons highlight differences that may have implications for vaccine production. IMPORTANCE: Hand-foot-and-mouth disease is a serious public health threat to children in Asian-Pacific countries, resulting in millions of cases. EV71 and CVA16 are the two dominant causative agents of the disease that, while usually mild, can cause severe neurological complications, leading to hundreds of deaths. EV71 vaccines do not provide protection against CVA16. A CVA16 vaccine or bivalent EV71/CVA16 vaccine is therefore urgently needed. We report atomic structures for the mature CVA16 virus, a natural empty particle, and a recombinant CVA16 virus-like particle that does not contain the viral genome. All three particles have similar structures and identical antigenicity. The recombinant particles, produced in insect cells (a system suitable for making vaccine antigen), are stabilized by recruiting from the insect cells a small molecule that is different from that used by the virus in a normal infection. We present structural and immunogenic comparisons with EV71 to facilitate structure based drug design and vaccine development. PMID- 26269178 TI - DDX60L Is an Interferon-Stimulated Gene Product Restricting Hepatitis C Virus Replication in Cell Culture. AB - All major types of interferon (IFN) efficiently inhibit hepatitis C virus (HCV) replication in vitro and in vivo. Remarkably, HCV replication is not sensitive to IFN-gamma in the hepatoma cell line Huh6, despite an intact signaling pathway. We performed transcriptome analyses between Huh6 and Huh-7 cells to identify effector genes of the IFN-gamma response and thereby identified the DExD/H box helicase DEAD box polypeptide 60-like (DDX60L) as a restriction factor of HCV replication. DDX60L and its homolog DEAD box polypeptide 60 (DDX60) were both induced upon viral infection and IFN treatment in primary human hepatocytes. However, exclusively DDX60L knockdown increased HCV replication in Huh-7 cells and rescued HCV replication from type II IFN as well as type I and III IFN treatment, suggesting that DDX60L is an important effector protein of the innate immune response against HCV. In contrast, we found no impact of DDX60L on replication of hepatitis A virus. DDX60L protein was detectable only upon strong ectopic overexpression, displayed a broad cytoplasmic distribution, but caused cytopathic effects under these conditions. DDX60L knockdown did not alter interferon-stimulated gene (ISG) induction after IFN treatment but inhibited HCV replication upon ectopic expression, suggesting that it is a direct effector of the innate immune response. It most likely inhibits viral RNA replication, since we found neither impact of DDX60L on translation or stability of HCV subgenomic replicons nor additional impact on assembly of infectious virus. Similar to DDX60, DDX60L had a moderate impact on RIG-I dependent activation of innate immunity, suggesting additional functions in the sensing of viral RNA. IMPORTANCE: Interferons induce a plethora of interferon-stimulated genes (ISGs), which are our first line of defense against viral infections. In addition, IFNs have been used in antiviral therapy, in particular against the human pathogen hepatitis C virus (HCV); still, their mechanism of action is not well understood, since diverse, overlapping sets of antagonistic effector ISGs target viruses with different biologies. Our work identifies DDX60L as a novel factor that inhibits replication of HCV. DDX60L expression is regulated similarly to that of its homolog DDX60, but our data suggest that it has distinct functions, since we found no contribution of DDX60 in combatting HCV replication. The identification of novel components of the innate immune response contributes to a comprehensive understanding of the complex mechanisms governing antiviral defense. PMID- 26269179 TI - Replication-Competent Controlled Herpes Simplex Virus. AB - We present the development and characterization of a replication-competent controlled herpes simplex virus 1 (HSV-1). Replication-essential ICP4 and ICP8 genes of HSV-1 wild-type strain 17syn+ were brought under the control of a dually responsive gene switch. The gene switch comprises (i) a transactivator that is activated by a narrow class of antiprogestins, including mifepristone and ulipristal, and whose expression is mediated by a promoter cassette that comprises an HSP70B promoter and a transactivator-responsive promoter and (ii) transactivator-responsive promoters that drive the ICP4 and ICP8 genes. Single step growth experiments in different cell lines demonstrated that replication of the recombinant virus, HSV-GS3, is strictly dependent on an activating treatment consisting of administration of a supraphysiological heat dose in the presence of an antiprogestin. The replication-competent controlled virus replicates with an efficiency approaching that of the wild-type virus from which it was derived. Essentially no replication occurs in the absence of activating treatment or if HSV-GS3-infected cells are exposed only to heat or antiprogestin. These findings were corroborated by measurements of amounts of viral DNA and transcripts of the regulated ICP4 gene and the glycoprotein C (gC) late gene, which was not regulated. Similar findings were made in experiments with a mouse footpad infection model. IMPORTANCE: The alphaherpesviruses have long been considered vectors for recombinant vaccines and oncolytic therapies. The traditional approach uses vector backbones containing attenuating mutations that restrict replication to ensure safety. The shortcoming of this approach is that the attenuating mutations tend to limit both the immune presentation and oncolytic properties of these vectors. HSV-GS3 represents a novel type of vector that, when activated, replicates with the efficiency of a nonattenuated virus and whose safety is derived from deliberate, stringent regulation of multiple replication essential genes. By directing activating heat to the region of virus administration, replication is strictly confined to infected cells within this region. The requirement for antiprogestin provides an additional level of safety, ensuring that virus replication cannot be triggered inadvertently. Replication competent controlled vectors such as HSV-GS3 may have the potential to be superior to conventional attenuated HSV vaccine and oncolytic vectors without sacrificing safety. PMID- 26269180 TI - Intermonomer Interactions in Hemagglutinin Subunits HA1 and HA2 Affecting Hemagglutinin Stability and Influenza Virus Infectivity. AB - Influenza virus hemagglutinin (HA) mediates virus entry by binding to cell surface receptors and fusing the viral and endosomal membranes following uptake by endocytosis. The acidic environment of endosomes triggers a large-scale conformational change in the transmembrane subunit of HA (HA2) involving a loop (B loop)-to-helix transition, which releases the fusion peptide at the HA2 N terminus from an interior pocket within the HA trimer. Subsequent insertion of the fusion peptide into the endosomal membrane initiates fusion. The acid stability of HA is influenced by residues in the fusion peptide, fusion peptide pocket, coiled-coil regions of HA2, and interactions between the surface (HA1) and HA2 subunits, but details are not fully understood and vary among strains. Current evidence suggests that the HA from the circulating pandemic 2009 H1N1 influenza A virus [A(H1N1)pdm09] is less stable than the HAs from other seasonal influenza virus strains. Here we show that residue 205 in HA1 and residue 399 in the B loop of HA2 (residue 72, HA2 numbering) in different monomers of the trimeric A(H1N1)pdm09 HA are involved in functionally important intermolecular interactions and that a conserved histidine in this pair helps regulate HA stability. An arginine-lysine pair at this location destabilizes HA at acidic pH and mediates fusion at a higher pH, while a glutamate-lysine pair enhances HA stability and requires a lower pH to induce fusion. Our findings identify key residues in HA1 and HA2 that interact to help regulate H1N1 HA stability and virus infectivity. IMPORTANCE: Influenza virus hemagglutinin (HA) is the principal antigen in inactivated influenza vaccines and the target of protective antibodies. However, the influenza A virus HA is highly variable, necessitating frequent vaccine changes to match circulating strains. Sequence changes in HA affect not only antigenicity but also HA stability, which has important implications for vaccine production, as well as viral adaptation to hosts. HA from the pandemic 2009 H1N1 influenza A virus is less stable than other recent seasonal influenza virus HAs, but the molecular interactions that contribute to HA stability are not fully understood. Here we identify molecular interactions between specific residues in the surface and transmembrane subunits of HA that help regulate the HA conformational changes needed for HA stability and virus entry. These findings contribute to our understanding of the molecular mechanisms controlling HA function and antigen stability. PMID- 26269182 TI - Flexibility of NS5 Methyltransferase-Polymerase Linker Region Is Essential for Dengue Virus Replication. AB - We examined the function of the conserved Val/Ile residue within the dengue virus NS5 interdomain linker (residues 263 to 272) by site-directed mutagenesis. Gly substitution or Gly/Pro insertion after the conserved residue increased the linker flexibility and created slightly attenuated viruses. In contrast, Pro substitution abolished virus replication by imposing rigidity in the linker and restricting NS5's conformational plasticity. Our biochemical and reverse genetics experiments demonstrate that NS5 utilizes conformational regulation to achieve optimum viral replication. PMID- 26269181 TI - Human Papillomavirus 18 Genetic Variation and Cervical Cancer Risk Worldwide. AB - Human papillomavirus 18 (HPV18) is the second most carcinogenic HPV type, after HPV16, and it accounts for approximately 12% of squamous cell carcinoma (SCC) as well as 37% of adenocarcinoma (ADC) of the cervix worldwide. We aimed to evaluate the worldwide diversity and carcinogenicity of HPV18 genetic variants by sequencing the entire long control region (LCR) and the E6 open reading frame of 711 HPV18-positive cervical samples from 39 countries, taking advantage of the International Agency for Research on Cancer biobank. A total of 209 unique HPV18 sequence variants were identified that formed three phylogenetic lineages (A, B, and C). A and B lineages each divided into four sublineages, including a newly identified candidate B4 sublineage. The distribution of lineages varied by geographical region, with B and C lineages found principally in Africa. HPV18 (sub)lineages were compared between 453 cancer cases and 236 controls, as well as between 81 ADC and 160 matched SCC cases. In region-stratified analyses, there were no significant differences in the distribution of HPV18 variant lineages between cervical cancer cases and controls or between ADC and SCC. In conclusion, our findings do not support the role of HPV18 (sub)lineages for discriminating cancer risk or explaining why HPV18 is more strongly linked with ADC than SCC. IMPORTANCE: This is the largest and most geographically/ethnically diverse study of the genetic variation of HPV18 to date, providing a comprehensive reference for phylogenetic classification of HPV18 sublineages for epidemiological and biological studies. PMID- 26269183 TI - Adenovirus E4-ORF1 Dysregulates Epidermal Growth Factor and Insulin/Insulin-Like Growth Factor Receptors To Mediate Constitutive Myc Expression. AB - The E4-ORF1 protein encoded by human adenovirus stimulates viral replication in human epithelial cells by binding and activating cellular phosphatidylinositol 3 kinase (PI3K) at the plasma membrane and cellular Myc in the nucleus. In this study, we showed that E4-ORF1 hijacks the tyrosine kinase activities of cellular epidermal growth factor receptor (EGFR) and insulin receptor (InsR)/insulin-like growth factor receptor 1 (IGF1R), as well as the lipid kinase activity of PI3K, to mediate constitutive Myc protein expression. We additionally demonstrated that EGFR contributes to constitutive Myc expression through the capacity of E4-ORF1 to induce ligand-independent EGFR activation and stimulation of the Ras/Mek/Erk pathway, the latter activity of which was conserved by human adenoviruses. Results further suggested that EGFR normally forms a complex with the cellular PDZ protein Discs Large 1 (Dlg1), a component of the Dlg1:E4-ORF1:PI3K ternary complex that mediates E4-ORF1-induced PI3K activation, and that E4-ORF1 binds the Dlg1:EGFR complex and promotes the association of EGFR with InsR and IGF1R. In addition to its role in constitutive Myc expression, InsR/IGF1R also negatively regulates EGFR autophosphorylation and EGFR-mediated Ras/Mek/Erk signaling, and data suggested that E4-ORF1 binding to Dlg1 antagonizes these activities. Collectively, our findings suggest that in human epithelial cells, E4-ORF1 targets EGFR, InsR/IGF1R, and PI3K at the plasma membrane to activate cytosolic signaling pathways that sustain Myc protein levels in the nucleus. We postulate that E4-ORF1-induced constitutive Myc expression functions to ensure the formation of nuclear E4-ORF1:Myc complexes, which have been shown to activate Myc and to enhance adenovirus replication. IMPORTANCE: While human adenoviruses primarily produce self-limited acute infections in humans, these agents are associated with life-threatening diseases in immunocompromised patients and in otherwise healthy individuals infected with certain virulent serotypes. The adenovirus E4-ORF1 protein enhances viral replication by activating the cellular lipid kinase PI3K and the cellular transcription factor Myc. Here we report that E4-ORF1 usurps the functions of the cellular tyrosine kinase receptors EGFR and InsR /: IGF1R, as well as PI3K, to sustain Myc protein expression in cells. Furthermore, sustained Myc expression depended on E4-ORF1-induced ligand independent EGFR activation that stimulated Ras/Mek/Erk signaling, a function found to be conserved by human adenoviruses. Given the established roles of PI3K, the Ras/Mek/Erk pathway, and Myc in the adenovirus life cycle, our findings may aid in the development of safer, more effective therapeutic strategies to treat severe adenovirus infections as well as improved adenovirus vectors for use in vaccination and gene and cancer therapy. PMID- 26269184 TI - Induction of Heme Oxygenase-1 Deficiency and Associated Glutamate-Mediated Neurotoxicity Is a Highly Conserved HIV Phenotype of Chronic Macrophage Infection That Is Resistant to Antiretroviral Therapy. AB - Expression of the cytoprotective enzyme heme oxygenase-1 (HO-1) is significantly reduced in the brain prefrontal cortex of HIV-positive individuals with HIV associated neurocognitive disorders (HAND). Furthermore, this HO-1 deficiency correlates with brain viral load, markers of macrophage activation, and type I interferon responses. In vitro, HIV replication in monocyte-derived macrophages (MDM) selectively reduces HO-1 protein and RNA expression and induces production of neurotoxic levels of glutamate; correction of this HO-1 deficiency reduces neurotoxic glutamate production without an effect on HIV replication. We now demonstrate that macrophage HO-1 deficiency, and the associated neurotoxin production, is a conserved feature of infection with macrophage-tropic HIV-1 strains that correlates closely with the extent of replication, and this feature extends to HIV-2 infection. We further demonstrate that this HO-1 deficiency does not depend specifically upon the HIV-1 accessory genes nef, vpr, or vpu but rather on HIV replication, even when markedly limited. Finally, antiretroviral therapy (ART) applied to MDM after HIV infection is established does not prevent HO-1 loss or the associated neurotoxin production. This work defines a predictable relationship between HIV replication, HO-1 loss, and neurotoxin production in MDM that likely reflects processes in place in the HIV-infected brains of individuals receiving ART. It further suggests that correcting this HO 1 deficiency in HIV-infected MDM could provide neuroprotection above that provided by current ART or proposed antiviral therapies directed at limiting Nef, Vpr, or Vpu functions. The ability of HIV-2 to reduce HO-1 expression suggests that this is a conserved phenotype among macrophage-tropic human immunodeficiency viruses that could contribute to neuropathogenesis. IMPORTANCE: The continued prevalence of HIV-associated neurocognitive disorders (HAND) underscores the need for adjunctive therapy that targets the neuropathological processes that persist in antiretroviral therapy (ART)-treated HIV-infected individuals. To this end, we previously identified one such possible process, a deficiency of the antioxidative and anti-inflammatory enzyme heme oxygenase-1 (HO-1) in the brains of individuals with HAND. In the present study, our findings suggest that the HO 1 deficiency associated with excess glutamate production and neurotoxicity in HIV infected macrophages is a highly conserved phenotype of macrophage-tropic HIV strains and that this phenotype can persist in the macrophage compartment in the presence of ART. This suggests a plausible mechanism by which HIV infection of brain macrophages in ART-treated individuals could exacerbate oxidative stress and glutamate-induced neuronal injury, each of which is associated with neurocognitive dysfunction in infected individuals. Thus, therapies that rescue the HO-1 deficiency in HIV-infected individuals could provide additional neuroprotection to ART. PMID- 26269186 TI - Generation of Live Attenuated Influenza Virus by Using Codon Usage Bias. AB - Seasonal influenza epidemics and occasional pandemics threaten public health worldwide. New alternative strategies for generating recombinant viruses with vaccine potential are needed. Interestingly, influenza viruses circulating in different hosts have been found to have distinct codon usage patterns, which may reflect host adaptation. We therefore hypothesized that it is possible to make a human seasonal influenza virus that is specifically attenuated in human cells but not in eggs by converting its codon usage so that it is similar to that observed from avian influenza viruses. This approach might help to generate human live attenuated viruses without affecting their yield in eggs. To test this hypothesis, over 300 silent mutations were introduced into the genome of a seasonal H1N1 influenza virus. The resultant mutant was significantly attenuated in mammalian cells and mice, yet it grew well in embryonated eggs. A single dose of intranasal vaccination induced potent innate, humoral, and cellular immune responses, and the mutant could protect mice against homologous and heterologous viral challenges. The attenuated mutant could also be used as a vaccine master donor strain by introducing hemagglutinin and neuraminidase genes derived from other strains. Thus, our approach is a successful strategy to generate attenuated viruses for future application as vaccines. IMPORTANCE: Vaccination has been one of the best protective measures in combating influenza virus infection. Current licensed influenza vaccines and their production have various limitations. Our virus attenuation strategy makes use of the codon usage biases of human and avian influenza viruses to generate a human-derived influenza virus that is attenuated in mammalian hosts. This method, however, does not affect virus replication in eggs. This makes the resultant mutants highly compatible with existing egg-based vaccine production pipelines. The viral proteins generated from the codon bias mutants are identical to the wild-type viral proteins. In addition, our massive genome-wide mutational approach further minimizes the concern over reverse mutations. The potential use of this kind of codon bias mutant as a master donor strain to generate other live attenuated viruses is also demonstrated. These findings put forward a promising live attenuated influenza vaccine generation strategy to control influenza. PMID- 26269185 TI - Severe Acute Respiratory Syndrome (SARS) Coronavirus ORF8 Protein Is Acquired from SARS-Related Coronavirus from Greater Horseshoe Bats through Recombination. AB - Despite the identification of horseshoe bats as the reservoir of severe acute respiratory syndrome (SARS)-related coronaviruses (SARSr-CoVs), the origin of SARS-CoV ORF8, which contains the 29-nucleotide signature deletion among human strains, remains obscure. Although two SARS-related Rhinolophus sinicus bat CoVs (SARSr-Rs-BatCoVs) previously detected in Chinese horseshoe bats (Rhinolophus sinicus) in Yunnan, RsSHC014 and Rs3367, possessed 95% genome identities to human and civet SARSr-CoVs, their ORF8 protein exhibited only 32.2 to 33% amino acid identities to that of human/civet SARSr-CoVs. To elucidate the origin of SARS-CoV ORF8, we sampled 348 bats of various species in Yunnan, among which diverse alphacoronaviruses and betacoronaviruses, including potentially novel CoVs, were identified, with some showing potential interspecies transmission. The genomes of two betacoronaviruses, SARSr-Rf-BatCoV YNLF_31C and YNLF_34C, from greater horseshoe bats (Rhinolophus ferrumequinum), possessed 93% nucleotide identities to human/civet SARSr-CoV genomes. Although these two betacoronaviruses displayed lower similarities than SARSr-Rs-BatCoV RsSHC014 and Rs3367 in S protein to civet SARSr-CoVs, their ORF8 proteins demonstrated exceptionally high (80.4 to 81.3%) amino acid identities to that of human/civet SARSr-CoVs, compared to SARSr BatCoVs from other horseshoe bats (23.2 to 37.3%). Potential recombination events were identified around ORF8 between SARSr-Rf-BatCoVs and SARSr-Rs-BatCoVs, leading to the generation of civet SARSr-CoVs. The expression of ORF8 subgenomic mRNA suggested that the ORF8 protein may be functional in SARSr-Rf-BatCoVs. The high Ka/Ks ratio among human SARS-CoVs compared to that among SARSr-BatCoVs supported that ORF8 is under strong positive selection during animal-to-human transmission. Molecular clock analysis using ORF1ab showed that SARSr-Rf-BatCoV YNLF_31C and YNLF_34C diverged from civet/human SARSr-CoVs in approximately 1990. SARS-CoV ORF8 originated from SARSr-CoVs of greater horseshoe bats through recombination, which may be important for animal-to-human transmission. IMPORTANCE: Although horseshoe bats are the primary reservoir of SARS-related coronaviruses (SARSr-CoVs), it is still unclear how these bat viruses have evolved to cross the species barrier to infect civets and humans. Most human SARS CoV epidemic strains contain a signature 29-nucleotide deletion in ORF8, compared to civet SARSr-CoVs, suggesting that ORF8 may be important for interspecies transmission. However, the origin of SARS-CoV ORF8 remains obscure. In particular, SARSr-Rs-BatCoVs from Chinese horseshoe bats (Rhinolophus sinicus) exhibited <40% amino acid identities to human/civet SARS-CoV in the ORF8 protein. We detected diverse alphacoronaviruses and betacoronaviruses among various bat species in Yunnan, China, including two SARSr-Rf-BatCoVs from greater horseshoe bats that possessed ORF8 proteins with exceptionally high amino acid identities to that of human/civet SARSr-CoVs. We demonstrated recombination events around ORF8 between SARSr-Rf-BatCoVs and SARSr-Rs-BatCoVs, leading to the generation of civet SARSr-CoVs. Our findings offer insight into the evolutionary origin of SARS CoV ORF8 protein, which was likely acquired from SARSr-CoVs of greater horseshoe bats through recombination. PMID- 26269187 TI - MicroRNA-Attenuated Clone of Virulent Semliki Forest Virus Overcomes Antiviral Type I Interferon in Resistant Mouse CT-2A Glioma. AB - Glioblastoma is a terminal disease with no effective treatment currently available. Among the new therapy candidates are oncolytic viruses capable of selectively replicating in cancer cells, causing tumor lysis and inducing adaptive immune responses against the tumor. However, tumor antiviral responses, primarily mediated by type I interferon (IFN-I), remain a key problem that severely restricts viral replication and oncolysis. We show here that the Semliki Forest virus (SFV) strain SFV4, which causes lethal encephalitis in mice, is able to infect and replicate independent of the IFN-I defense in mouse glioblastoma cells and cell lines originating from primary human glioblastoma patient samples. The ability to tolerate IFN-I was retained in SFV4-miRT124 cells, a derivative cell line of strain SFV4 with a restricted capacity to replicate in neurons due to insertion of target sites for neuronal microRNA 124. The IFN-I tolerance was associated with the viral nsp3-nsp4 gene region and distinct from the genetic loci responsible for SFV neurovirulence. In contrast to the naturally attenuated strain SFV A7(74) and its derivatives, SFV4-miRT124 displayed increased oncolytic potency in CT-2A murine astrocytoma cells and in the human glioblastoma cell lines pretreated with IFN-I. Following a single intraperitoneal injection of SFV4 miRT124 into C57BL/6 mice bearing CT-2A orthotopic gliomas, the virus homed to the brain and was amplified in the tumor, resulting in significant tumor growth inhibition and improved survival. IMPORTANCE: Although progress has been made in development of replicative oncolytic viruses, information regarding their overall therapeutic potency in a clinical setting is still lacking. This could be at least partially dependent on the IFN-I sensitivity of the viruses used. Here, we show that the conditionally replicating SFV4-miRT124 virus shares the IFN-I tolerance of the pathogenic wild-type SFV, thereby allowing efficient targeting of a glioma that is refractory to naturally attenuated therapy vector strains sensitive to IFN-I. This is the first evidence of orthotopic syngeneic mouse glioma eradication following peripheral alphavirus administration. Our findings indicate a clear benefit in harnessing the wild-type virus replicative potency in development of next-generation oncolytic alphaviruses. PMID- 26269188 TI - Enhanced Influenza Virus-Like Particle Vaccination with a Structurally Optimized RIG-I Agonist as Adjuvant. AB - The molecular interaction between viral RNA and the cytosolic sensor RIG-I represents the initial trigger in the development of an effective immune response against infection with RNA viruses, resulting in innate immune activation and subsequent induction of adaptive responses. In the present study, the adjuvant properties of a sequence-optimized 5'-triphosphate-containing RNA (5'pppRNA) RIG I agonist (termed M8) were examined in combination with influenza virus-like particles (VLP) (M8-VLP) expressing H5N1 influenza virus hemagglutinin (HA) and neuraminidase (NA) as immunogens. In combination with VLP, M8 increased the antibody response to VLP immunization, provided VLP antigen sparing, and protected mice from a lethal challenge with H5N1 influenza virus. M8-VLP immunization also led to long-term protective responses against influenza virus infection in mice. M8 adjuvantation of VLP increased endpoint and antibody titers and inhibited influenza virus replication in lungs compared with approved or experimental adjuvants alum, AddaVax, and poly(I.C). Uniquely, immunization with M8-VLP stimulated a TH1-biased CD4 T cell response, as determined by increased TH1 cytokine levels in CD4 T cells and increased IgG2 levels in sera. Collectively, these data demonstrate that a sequence-optimized, RIG-I-specific agonist is a potent adjuvant that can be utilized to increase the efficacy of influenza VLP vaccination and dramatically improve humoral and cellular mediated protective responses against influenza virus challenge. IMPORTANCE: The development of novel adjuvants to increase vaccine immunogenicity is an important goal that seeks to improve vaccine efficacy and ultimately prevent infections that endanger human health. This proof-of-principle study investigated the adjuvant properties of a sequence-optimized 5'pppRNA agonist (M8) with enhanced capacity to stimulate antiviral and inflammatory gene networks using influenza virus-like particles (VLP) expressing HA and NA as immunogens. Vaccination with VLP in combination with M8 increased anti-influenza virus antibody titers and protected animals from lethal influenza virus challenge, highlighting the potential clinical use of M8 as an adjuvant in vaccine development. Altogether, the results describe a novel immunostimulatory agonist targeted to the cytosolic RIG-I sensor as an attractive vaccine adjuvant candidate that can be used to increase vaccine efficacy, a pressing issue in children and the elderly population. PMID- 26269189 TI - The Breadth of Expandable Memory CD8+ T Cells Inversely Correlates with Residual Viral Loads in HIV Elite Controllers. AB - Previous studies have shown that elite controllers with minimal effector T cell responses harbor a low-frequency, readily expandable, highly functional, and broadly directed memory population. Here, we interrogated the in vivo relevance of this cell population by investigating whether the breadth of expandable memory responses is associated with the magnitude of residual viremia in individuals achieving durable suppression of HIV infection. HIV-specific memory CD8(+) T cells were expanded by using autologous epitopic and variant peptides. Viral load was measured by an ultrasensitive single-copy PCR assay. Following expansion, controllers showed a greater increase in the overall breadth of Gag responses than did untreated progressors (P = 0.01) as well as treated progressors (P = 0.0003). Nef- and Env-specific memory cells expanded poorly for all groups, and their expanded breadths were indistinguishable among groups (P = 0.9 for Nef as determined by a Kruskal-Wallis test; P = 0.6 for Env as determined by a Kruskal Wallis test). More importantly, we show that the breadth of expandable, previously undetectable Gag-specific responses was inversely correlated with residual viral load (r = -0.6; P = 0.009). Together, these data reveal a direct link between the abundance of Gag-specific expandable memory responses and prolonged maintenance of low-level viremia. Our studies highlight a CD8(+) T cell feature that would be desirable in a vaccine-induced T cell response. IMPORTANCE: Many studies have shown that the rare ability of some individuals to control HIV infection in the absence of antiretroviral therapy appears to be heavily dependent upon special HIV-specific killer T lymphocytes that are able to inhibit viral replication. The identification of key features of these immune cells has the potential to inform rational HIV vaccine design. This study shows that a special subset of killer lymphocytes, known as central memory CD8(+) T lymphocytes, is at least partially involved in the durable control of HIV replication. HIV controllers maintain a large proportion of Gag-specific expandable memory CD8(+) T cells involved in ongoing viral suppression. These data suggest that induction of this cell subset by future HIV vaccines may be important for narrowing possible routes of rapid escape from vaccine-induced CD8(+) T cell responses. PMID- 26269190 TI - Encapsidation of Host RNAs by Cucumber Necrosis Virus Coat Protein during both Agroinfiltration and Infection. AB - Next-generation sequence analysis of virus-like particles (VLPs) produced during agroinfiltration of cucumber necrosis virus (CNV) coat protein (CP) and of authentic CNV virions was conducted to assess if host RNAs can be encapsidated by CNV CP. VLPs containing host RNAs were found to be produced during agroinfiltration, accumulating to approximately 1/60 the level that CNV virions accumulated during infection. VLPs contained a variety of host RNA species, including the major rRNAs as well as cytoplasmic, chloroplast, and mitochondrial mRNAs. The most predominant host RNA species encapsidated in VLPs were chloroplast encoded, consistent with the efficient targeting of CNV CP to chloroplasts during agroinfiltration. Interestingly, droplet digital PCR analysis showed that the CNV CP mRNA expressed during agroinfiltration was the most efficiently encapsidated mRNA, suggesting that the CNV CP open reading frame may contain a high-affinity site or sites for CP binding and thus contribute to the specificity of CNV RNA encapsidation. Approximately 0.09% to 0.7% of the RNA derived from authentic CNV virions contained host RNA, with chloroplast RNA again being the most prominent species. This is consistent with our previous finding that a small proportion of CNV CP enters chloroplasts during the infection process and highlights the possibility that chloroplast targeting is a significant aspect of CNV infection. Remarkably, 6 to 8 of the top 10 most efficiently encapsidated nucleus-encoded RNAs in CNV virions correspond to retrotransposon or retrotransposon-like RNA sequences. Thus, CNV could potentially serve as a vehicle for horizontal transmission of retrotransposons to new hosts and thereby significantly influence genome evolution. IMPORTANCE: Viruses predominantly encapsidate their own virus-related RNA species due to the possession of specific sequences and/or structures on viral RNA which serve as high-affinity binding sites for the coat protein. In this study, we show, using next-generation sequence analysis, that CNV also encapsidates host RNA species, which account for ~0.1% of the RNA packaged in CNV particles. The encapsidated host RNAs predominantly include chloroplast RNAs, reinforcing previous observations that CNV CP enters chloroplasts during infection. Remarkably, the most abundantly encapsidated cytoplasmic mRNAs consisted of retrotransposon-like RNA sequences, similar to findings recently reported for flock house virus (A. Routh, T. Domitrovic, and J. E. Johnson, Proc Natl Acad Sci U S A 109:1907-1912, 2012). Encapsidation of retrotransposon sequences may contribute to their horizontal transmission should CNV virions carrying retrotransposons infect a new host. Such an event could lead to large-scale genomic changes in a naive plant host, thus facilitating host evolutionary novelty. PMID- 26269191 TI - Increased Immune Response Variability during Simultaneous Viral Coinfection Leads to Unpredictability in CD8 T Cell Immunity and Pathogenesis. AB - T cell memory is usually studied in the context of infection with a single pathogen in naive mice, but how memory develops during a coinfection with two pathogens, as frequently occurs in nature or after vaccination, is far less studied. Here, we questioned how the competition between immune responses to two viruses in the same naive host would influence the development of CD8 T cell memory and subsequent disease outcome upon challenge. Using two different models of coinfection, including the well-studied lymphocytic choriomeningitis (LCMV) and Pichinde (PICV) viruses, several differences were observed within the CD8 T cell responses to either virus. Compared to single-virus infection, coinfection resulted in substantial variation among mice in the size of epitope-specific T cell responses to each virus. Some mice had an overall reduced number of virus specific cells to either one of the viruses, and other mice developed an immunodominant response to a normally subdominant, cross-reactive epitope (nucleoprotein residues 205 to 212, or NP205). These changes led to decreased protective immunity and enhanced pathology in some mice upon challenge with either of the original coinfecting viruses. In mice with PICV-dominant responses, during a high-dose challenge with LCMV clone 13, increased immunopathology was associated with a reduced number of LCMV-specific effector memory CD8 T cells. In mice with dominant cross-reactive memory responses, during challenge with PICV increased immunopathology was directly associated with these cross-reactive NP205 specific CD8 memory cells. In conclusion, the inherent competition between two simultaneous immune responses results in significant alterations in T cell immunity and subsequent disease outcome upon reexposure. IMPORTANCE: Combination vaccines and simultaneous administration of vaccines are necessary to accommodate required immunizations and maintain vaccination rates. Antibody responses generally correlate with protection and vaccine efficacy. However, live attenuated vaccines also induce strong CD8 T cell responses, and the impact of these cells on subsequent immunity, whether beneficial or detrimental, has seldom been studied, in part due to the lack of known T cell epitopes to vaccine viruses. We questioned if the inherent increased competition and stochasticity between two immune responses during a simultaneous coinfection would significantly alter CD8 T cell memory in a mouse model where CD8 T cell epitopes are clearly defined. We show that some of the coinfected mice have sufficiently altered memory T cell responses that they have decreased protection and enhanced immunopathology when reexposed to one of the two viruses. These data suggest that a better understanding of human T cell responses to vaccines is needed to optimize immunization strategies. PMID- 26269192 TI - Propranolol Decreases Proliferation of Endothelial Cells Transformed by Kaposi's Sarcoma-Associated Herpesvirus and Induces Lytic Viral Gene Expression. AB - Kaposi's sarcoma (KS) is common in Africa, but economic constraints hinder successful treatment in most patients. Propranolol, a generic beta-adrenergic antagonist, decreased proliferation of KS-associated herpesvirus (KSHV)-infected cells. Downregulation of cyclin A2 and cyclin-dependent kinase 1 (CDK1) recapitulated this phenotype. Additionally, propranolol induced lytic gene expression in association with downregulation of CDK6. Thus, propranolol has diverse effects on KSHV-infected cells, and this generic drug has potential as a therapeutic agent for KS. PMID- 26269194 TI - Syringocystadenoma papilliferum of the male nipple. AB - Syringocystadenoma papilliferum (SP) is a rare and benign cutaneous adnexal tumor, particularly infrequent in the breast, with only one previous case affecting a female nipple. The present tumor was located at the nipple of a 23 year-old man. This tumor consisted of several cysts and satisfied the characteristic microscopic features of SP: numerous papillary projections of double-layered glandular epithelium and a fibrovascular core with lymphoplasmacytic infiltration. Interestingly, many cysts were lined by stratified squamous epithelium with transition to glandular epithelium. Immunohistochemically, almost all structures were negative for gross cystic disease fluid protein-15, androgen receptor, estrogen receptor and progesterone receptor. The immunoprofiles of glandular epithelium were inadequate for the mature two-cell pattern of skin adnexal glands and mammary glands; most basal cuboidal cells lacked alpha-smooth muscle actin, and some of the luminal columnar cells were negative for cytokeratin 7 and cytokeratin 19. The clinical and pathological features of this uncommon tumor are presented, along with a review of the literature of SP of the breast. PMID- 26269193 TI - The role for gut permeability in the pathogenesis of type 1 diabetes--a solid or leaky concept? AB - Increasing evidence, both functional and morphological, supports the concept of increased intestinal permeability as an intrinsic characteristic of type 1 diabetes (T1D) in both humans and animal models of the disease. Often referred to as a 'leaky gut', its mechanistic impact on the pathogenesis of T1D remains unclear. Hypotheses that this defect influences immune responses against antigens (both self and non-self) predominate, yet others argue hyperglycemia and insulitis may contribute to increased gut permeability in T1D. To address these complicated issues, we herein review the many conceptual role(s) for a leaky gut in the pathogenesis of T1D and suggest ways that if true, therapeutic interventions aimed at the gut-pancreas axis may prove promising for future therapeutic interventions. PMID- 26269195 TI - Reduced cortical neurotransmitter receptor complex levels in fetal Down syndrome brain. AB - In this study, cortical receptor complex levels were determined in fetal Down syndrome (DS, trisomy 21) brain. Frontal cortices were obtained from individuals with DS (19th-22nd week of gestation) and controls. Membrane proteins were extracted, assayed on blue native gels and immunoblotted with brain receptor antibodies. Levels of a D1R-containing complex were markedly decreased in male and female cortices of DS individuals. Females with DS had significant reductions of nicotinic acetylcholine receptors alpha4 and alpha7, NMDA receptor GluN1 and AMPA receptor GluA1- and GluA3-containing receptor complexes. Levels of other brain receptor complexes (5-hydroxytryptamine 1A, GluA2 and GluR4 receptor containing complexes) were comparable between the groups of females. Levels of GluA2- and GluA3-containing complexes were significantly increased in males. Decreased levels of D1R complexes in both sexes, along with the significant reduction of alpha4, alpha7-containing receptor complexes observed in females, may explain the brain deficits and impaired cognition observed in DS. PMID- 26269196 TI - Photovoltaic performance and the energy landscape of CH3NH3PbI3. AB - Photovoltaic cells with absorbing layers of certain perovskites have power conversion efficiencies up to 20%. Among these materials, CH3NH3PbI3 is widely used. Here we use density-functional theory to calculate the energies and rotational energy barriers of a methylammonium ion in the alpha or beta phase of CH3NH3PbI3 with differently oriented neighbouring methylammonium ions. Our results suggest the methylammonium ions in CH3NH3PbI3 prefer to rotate collectively, and to be parallel to their neighbours. Changes in polarization on rotation of methylammonium ions are two to three times larger than those on relaxation of the lead ion from the centre of its coordination shell. The preferences for parallel configuration and concerted rotation, with the polarisation changes, are consistent with ferroelectricity in the material, and indicate that this polarisation is governed by methylammonium orientational correlations. We show that the field due to this polarisation is strong enough to screen the field hindering charge transport, and find this screening field in agreement with experiment. We examine two possible mechanisms for the effect of methylammonium ion rotation on photovoltaic performance. One is that rearrangement of methylammoniums promotes the creation and transport of charge carriers. Some effective masses change greatly, but changes in band structure with methylammonium rotation are not large enough to explain current-voltage hysteresis behaviour. The second possible mechanism is that polarization screens the hindering electric field, which arises from charge accumulation in the transport layers. Polarization changes on methylammonium rotation favour this second mechanism, suggesting that collective reorientation of methylammonium ions in the bulk crystal are in significant part responsible for the hysteresis and power conversion characteristics of CH3NH3PbI3 photovoltaic cells. PMID- 26269197 TI - Rhesus macaque theta-defensin RTD-1 inhibits proinflammatory cytokine secretion and gene expression by inhibiting the activation of NF-kappaB and MAPK pathways. AB - theta-Defensins are pleiotropic, macrocyclic peptides that are expressed uniquely in Old World monkeys. The peptides are potent, broad-spectrum microbicides that also modulate inflammatory responses in vitro and in animal models of viral infection and polymicrobial sepsis. theta-Defensins suppress proinflammatory cytokine secretion by leukocytes stimulated with diverse Toll-like receptor (TLR) ligands. Studies were performed to delineate anti-inflammatory mechanisms of rhesus theta-defensin 1 (RTD-1), the most abundant theta-defensin isoform in macaque granulocytes. RTD-1 reduced the secretion of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-8 in lipopolysaccharide (LPS) stimulated human blood monocytes and THP-1 macrophages, and this was accompanied by inhibition of nuclear factor kappaB (NF-kappaB) activation and mitogen activated protein kinase (MAPK) pathways. Peptide inhibition of NF-kappaB activation occurred following stimulation of extracellular (TLRs 1/2 and 4) and intracellular (TLR9) receptors. Although RTD-1 did not inhibit MAPK in unstimulated cells, it induced phosphorylation of Akt in otherwise untreated monocytes and THP-1 cells. In the latter, this occurred within 10 min of RTD-1 treatment and produced a sustained elevation of phosphorylated Akt (pAkt) for at least 4 h. pAkt is a negative regulator of MAPK and NF-kappaB activation. RTD-1 inhibited IkappaBalpha degradation and p38 MAPK phosphorylation, and stimulated Akt phosphorylation in LPS-treated human primary monocytes and THP-1 macrophages. Specific inhibition of phosphatidylinositol 3-kinase (PI3K) blocked RTD-1 stimulated Akt phosphorylation and reversed the suppression of NF-kappaB activation by the peptide. These studies indicate that the anti-inflammatory properties of theta-defensins are mediated by activation of the PI3K/Akt pathway and suppression of proinflammatory signals in immune-stimulated cells. PMID- 26269199 TI - Effect of acetaminophen on CGM glucose in an outpatient setting. PMID- 26269200 TI - Hydrogen reverses the clustering tendency of carbon in amorphous silicon oxycarbide. AB - Amorphous silicon oxycarbide (SiOC) is of great technological interest. However, its atomic-level structure is not well understood. Using density functional theory calculations, we show that the clustering tendency of C atoms in SiOC is extremely sensitive to hydrogen (H): without H, the C-C interaction is attractive, leading to enrichment of aggregated SiC4 tetrahedral units; with hydrogen, the C-C interaction is repulsive, leading to enrichment of randomly distributed SiCO3 tetrahedral units. Our results suggest that conflicting experimental characterizations of C distributions may be due to differing amounts of H present in the samples investigated. Our work also opens a path for tailoring the properties of SiOC by using the total H content to control the C distribution. PMID- 26269198 TI - Sulforaphane inhibits multiple inflammasomes through an Nrf2-independent mechanism. AB - The inflammasomes are intracellular complexes that have an important role in cytosolic innate immune sensing and pathogen defense. Inflammasome sensors detect a diversity of intracellular microbial ligands and endogenous danger signals and activate caspase-1, thus initiating maturation and release of the proinflammatory cytokines interleukin-1beta and interleukin-18. These events, although crucial to the innate immune response, have also been linked to the pathology of several inflammatory and autoimmune disorders. The natural isothiocyanate sulforaphane, present in broccoli sprouts and available as a dietary supplement, has gained attention for its antioxidant, anti-inflammatory, and chemopreventive properties. We discovered that sulforaphane inhibits caspase-1 autoproteolytic activation and interleukin-1beta maturation and secretion downstream of the nucleotide-binding oligomerization domain-like receptor leucine-rich repeat proteins NLRP1 and NLRP3, NLR family apoptosis inhibitory protein 5/NLR family caspase-1 recruitment domain-containing protein 4 (NAIP5/NLRC4), and absent in melanoma 2 (AIM2) inflammasome receptors. Sulforaphane does not inhibit the inflammasome by direct modification of active caspase-1 and its mechanism is not dependent on protein degradation by the proteasome or de novo protein synthesis. Furthermore, sulforaphane-mediated inhibition of the inflammasomes is independent of the transcription factor nuclear factor erythroid-derived 2-like factor 2 (Nrf2) and the antioxidant response-element pathway, to which many of the antioxidant and anti-inflammatory effects of sulforaphane have been attributed. Sulforaphane was also found to inhibit cell recruitment to the peritoneum and interleukin-1beta secretion in an in vivo peritonitis model of acute gout and to reverse NLRP1 mediated murine resistance to Bacillus anthracis spore infection. These findings demonstrate that sulforaphane inhibits the inflammasomes through a novel mechanism and contributes to our understanding of the beneficial effects of sulforaphane. PMID- 26269201 TI - Mid-term results of previously cemented hip arthroplasties revised with uncemented modular femoral components: a retrospective study. AB - BACKGROUND: We evaluated the mid-term results of previously cemented hip arthroplasties revised with uncemented modular femoral components. METHODS: The study included 40 patients (36 females (90 %) and 4 males (10 %), mean age 67.6 years, range 39-87 years) who underwent revision of a previously cemented hip prosthesis with an uncemented modular femoral stem between 2005 and 2009. The indications for revision were femoral aseptic loosening in 38 (95 %) cases and acetabular protrusion in 2 (5 %). According to the Paprosky classification, the femoral defect was type 1 in 10 (25 %) patients, type 2 in 16 (40 %), type 3a in 11 (27.5 %), type 3b in 2 (5 %) and type 4 in 1 (2.5 %). The Harris hip score was used for the clinical evaluation. Femoral vertical subsidence, the cortical index and femoral stem stability were assessed radiologically. The mean follow-up period was 84 months (range 61-95 months). RESULTS: The mean Harris hip score was 41.4 (range 35.4-44.4) preoperatively and 80.9 (range 65.6-98.3) at the final follow-up examination (p < 0.05). Mean vertical subsidence was 5.7 mm (range 2.5 10.5 mm) in seven (17.5 %) patients. Stable bone fixation was observed in 38 (95 %) patients, fibrous stable fixation in 2 (5 %) and no instability in any patient. Radiographs taken during the early postoperative period revealed that the cortical index was a mean of 1.34 (range 1.11-1.73) and a mean of 1.55 on the final follow-up radiographic examinations (range 1.16-1.91) (p < 0.01). CONCLUSIONS: Satisfactory results were achieved using uncemented modular femoral components during revision of previously cemented femoral components. Many modular femoral stems provide primary stability by filling femoral bone losses and help determine stem length, offset and anteversion. PMID- 26269202 TI - Assessment of the rocker sole shoes on postural stability in diabetic patients with distal sensory neuropathy. PMID- 26269203 TI - Injury patterns and outcomes following pediatric bicycle accidents. AB - OBJECTIVES: Other than automobiles, bicycles are connected to more pediatric injuries than any other consumer product. Whereas characterization of injury patterns following motor vehicle accidents has led to safety initiatives and treatment guidelines, knowledge related to bicyclist injuries is lacking. Our purpose is to identify major injury patterns and outcomes associated with pediatric bicycle accidents. METHODS: From January 2000 to December 2012, 1934 consecutive pediatric admissions (<=17 years) at a level I trauma center were retrospectively reviewed for mechanism injury, demographics, and outcomes. Parametric data were analyzed with student's t test and are presented as mean +/- standard deviation. Nonparametric data were analyzed with Mann-Whitney-U test and are presented as median (interquartile range). Analysis was performed to recognize injury patterns and outcomes significantly associated with bicycle related accidents. RESULTS: 80 pediatric patients were admitted following bicycle related trauma (4% of all pediatric trauma admissions). The cohort was age 11 +/- 4 years, ISS 11 +/- 10, 48% black, and 81% male. Injury patterns included 21% isolated head, 21% isolated abdominal, 13% isolated extremity, and 34% multiple injuries. 5% were age 0-4 years, 35% were age 5-9 years, 45% were 10-14 years, and 15% were 15-17 years (p < 0.001). 16% required operative intervention (6% abdominal, 9% orthopedic, 1% vascular). Children under age 6 required an abdominal operation 20% of the time. Length of stay was 2 (4) days with a mortality of 2.5%. CONCLUSIONS: Pediatric bicycle accidents more commonly occur in male children aged 10-14 years. Orthopedic injury is the most frequent overall indication for surgery, yet the youngest children more often required an abdominal operation. LEVEL OF EVIDENCE: Level III. PMID- 26269205 TI - Hairy cell leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PMID- 26269204 TI - EGFR-independent mechanisms of acquired resistance to AZD9291 in EGFR T790M positive NSCLC patients. AB - BACKGROUND: AZD9291 is an oral, irreversible, mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKI), which specifically targets both sensitizing and resistant T790M mutations. This compound has shown outstanding activity, in a phase I/II (AURA) trial. However, despite impressive tumor responses in T790M-positive patients, acquired resistance to this drug limits the benefit of this compound. Mutations at the EGFR C797 codon, located within the kinase-binding site, were very recently reported to be a potential mechanism of resistance to AZD9291 in T790M-positive patients. PATIENTS AND METHODS: To identify potential mechanisms of resistance to AZD9291, we report here on two patients with resistant biopsy specimens that had been treated with AZD9291. RESULTS: We identified in two distinct cases, HER2 and MET amplification by FISH and CGH as a potential mechanism of acquired resistance to third generation EGFR-TKI. Interestingly, this event occurred with complete loss of the T790M mutation. In one case, we observed a different molecular status at two biopsy sites (the T790M mutation at the primary site and wild-type T790M at the metastatic site with different pathways of acquired resistance to AZD9291). CONCLUSION: Our observations suggest that T790M-positive and wild-type T790M clones may coexist at baseline. AZD9291 efficiently suppresses the growth of T790M-positive cells, but a population of wild-type T790M cells at baseline will mediate the development of resistance, here via a by-pass pathway activating either HER2 or MET. PMID- 26269206 TI - The interface makes a difference: lanthanide ion coated vesicles hydrolyze phosphodiesters. AB - Lanthanide ions are strong Lewis acids. Their complexation to a variety of ligands can further enhance their Lewis acidity allowing the hydrolysis of phosphoesters and even DNA. We show that the interaction of lanthanide ions with vesicles from zwitterionic phosphatidylcholine lipids gives supramolecular structures in which the metal ion is loosely coordinated to the surface. This assembly provides a high density of Lewis-acidic metal centres, which hydrolyze phosphodiesters with enhanced rates. PMID- 26269207 TI - Java project on periodontal diseases: causes of tooth loss in a cohort of untreated individuals. AB - OBJECTIVE: To assess the relative contribution of caries and periodontal disease to tooth loss over 24 years in a cohort deprived of regular dental care. MATERIAL & METHODS: The study population consisted of 98 subjects from a tea estate on West Java, Indonesia, that had been part of a prospective longitudinal study and provided full datasets of clinical assessments between 1987, 1994 and 2002. In 2011, complete sets of dental radiographs were made which was combined with the survey forms and clinical slides from the previous assessments in order to estimate reasons for tooth loss. RESULTS: Thirty-seven subjects lost no teeth, whereas 61 subjects lost 185 teeth. In this group, 45.9% lost <=2 teeth, 32.8% lost 3 to 4 teeth and 19.7% lost >=5 teeth. The majority of teeth were lost due to caries. In five subjects, tooth loss could be attributed solely to periodontitis, whereas in four subjects teeth were lost due to both caries and periodontits. Analyses of the predictor variables age, gender, smoking, education, presence of caries and severe periodontitis showed that male gender and caries were significantly associated with tooth loss. CONCLUSION: The majority of teeth in this population were lost due to caries. PMID- 26269208 TI - Exciton Diffusion in Conjugated Polymers: From Fundamental Understanding to Improvement in Photovoltaic Conversion Efficiency. AB - Singlet exciton diffusion plays a central role in the photovoltaic conversion in organic photovoltaics (OPVs). Upon light absorption, singlet excitons are promptly generated in organic materials instead of charge carriers because the dielectric constant (epsilonr) is small (~3-4), which is in sharp contrast to inorganic and perovskite solar cells. In order to convert to charge carriers, excitons need to diffuse into an interface between electron donor and acceptor materials before deactivating to the ground state. Therefore, fundamental understanding of exciton diffusion dynamics is one of the most important issues to further improve OPVs. We highlight recent leading studies in this field and describe several approaches for efficient exciton harvesting at the interface in OPVs. PMID- 26269209 TI - Epithelial cell adhesion molecule-1 (ECAM1) is required in the maintenance of corneal epithelial barrier integrity. AB - Corneal epithelial barrier integrity is critical in the maintenance of the corneal homeostasis. The corneal barrier dysfunction may be associated with the pathogenesis of a number of eye diseases. In this study, we assessed the expression of epithelial cell adhesion molecule-1 (ECAM1) in human corneal epithelial cells (HCE). The epithelial barrier function of the corneal epithelial monolayer was determined in Transwells. We found that the HCE cells expressed ECAM1. Knockdown of ECAM1 markedly compromised the HCE monolayer barrier function. A complex of ECAM1, claudin1, and occludin was detected in the HCE monolayers, which was not detected in the ECAM1-null HCE monolayers. Exposure to the proinflammatory cytokine, interleukin-13, inhibited the expression of ECAM1 in HCE cells and compromised the barrier function, which was prevented in the HCE monolayer with the ECAM1 overexpression. In conclusion, ECAM1 is required in the formation of the tight junction complex and maintaining the corneal epithelial barrier function. PMID- 26269210 TI - Concurrent recording of RF pulses and gradient fields - comprehensive field monitoring for MRI. AB - Reconstruction of MRI data is based on exact knowledge of all magnetic field dynamics, since the interplay of RF and gradient pulses generates the signal, defines the contrast and forms the basis of resolution in spatial and spectral dimensions. Deviations caused by various sources, such as system imperfections, delays, eddy currents, drifts or externally induced fields, can therefore critically limit the accuracy of MRI examinations. This is true especially at ultra-high fields, because many error terms scale with the main field strength, and higher available SNR renders even smaller errors relevant. Higher baseline field also often requires higher acquisition bandwidths and faster signal encoding, increasing hardware demands and the severity of many types of hardware imperfection. To address field imperfections comprehensively, in this work we propose to expand the concept of magnetic field monitoring to also encompass the recording of RF fields. In this way, all dynamic magnetic fields relevant for spin evolution are covered, including low- to audio-frequency magnetic fields as produced by main magnets, gradients and shim systems, as well as RF pulses generated with single- and multiple-channel transmission systems. The proposed approach permits field measurements concurrently with actual MRI procedures on a strict common time base. The combined measurement is achieved with an array of miniaturized field probes that measure low- to audio-frequency fields via (19) F NMR and simultaneously pick up RF pulses in the MRI system's (1) H transmit band. Field recordings can form the basis of system calibration, retrospective correction of imaging data or closed-loop feedback correction, all of which hold potential to render MRI more robust and relax hardware requirements. The proposed approach is demonstrated for a range of imaging methods performed on a 7 T human MRI system, including accelerated multiple-channel RF pulses. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26269212 TI - A Narrow QRS Complex Tachycardia With Variable AV Relationships: What Is the Mechanism? PMID- 26269211 TI - Time course of facial emotion processing in women with borderline personality disorder: an ERP study. AB - BACKGROUND: Borderline personality disorder (BPD) is characterized by a negative perception of others. Previous studies have revealed deficits and biases in facial emotion recognition. This study investigates the behavioural and electrophysiological correlates underlying facial emotion processing in individuals with BPD. METHODS: The present study was conducted between July 2012 and May 2014. In an emotion classification task, unmedicated female patients with BPD as well as healthy women had to classify faces displaying blends of anger and happiness while the electroencephalogram was recorded. We analyzed visual event related potentials (ERPs) reflecting early (P100), structural (N170) and categorical (P300) facial processing in addition to behavioural responses. RESULTS: We included 36 women with BPD and 29 controls in our analysis. Patients with BPD were more likely than controls to classify predominantly happy faces as angry. Independent of facial emotion, women with BPD showed enhanced early occipital P100 amplitudes. Additionally, temporo-occipital N170 amplitudes were reduced at right hemispherical electrode sites. Centroparietal P300 amplitudes were reduced particularly for predominantly happy faces and increased for highly angry faces in women with BPD, whereas in healthy volunteers this component was modulated by both angry and happy facial affect. LIMITATIONS: Our sample included only women, and no clinical control group was investigated. CONCLUSION: Our findings suggest reduced thresholds for facial anger and deficits in the discrimination of facial happiness in individuals with BPD. This biased perception is associated with alterations in very early visual as well as deficient structural and categorical processing of faces. The current data could help to explain the negative perception of others that may be related to the patients' impairments in interpersonal functioning. PMID- 26269213 TI - Energy landscape investigation by wavelet transform analysis of atomic force spectroscopy data in a biorecognition experiment. AB - Force fluctuations recorded in an atomic force spectroscopy experiment, during the approach of a tip functionalized with biotin towards a substrate charged with avidin, have been analyzed by a wavelet transform. The observation of strong transient changes only when a specific biorecognition process between the partners takes place suggests a drastic modulation of the force fluctuations when biomolecules recognize each other. Such an analysis allows to investigate the peculiar features of a biorecognition process. These results are discussed in connection with the possible role of energy minima explored by biomolecules during the biorecognition process. PMID- 26269214 TI - Nutrition-dependent phenotypes affect sexual selection in a ladybird. AB - Environmental factors play a crucial role in influencing sexual selection in insects and the evolution of their mating systems. Although it has been reported that sexual selection in insects may change in response to varying environments, the reason for these changes remains poorly understood. Here, we focus on the mate selection process of a ladybird, Cryptolaemus montrouzieri, when experiencing low- and high-nutrition diet regimes both in its larval and adult stages. We found that female ladybirds preferred to mate with males reared under high-nutrition diet regimes, regardless of the nutritional conditions they experienced during their own larval stages, indicating that mate choice of female C. montrouzieri is non-random and phenotype-dependent. Such mate choice may depend on visual cues (body or genitalia size) and/or chemical cues (pheromones). Further, females from high-nutrition larval diet regimes produced more eggs than those from low-nutrition larval diet regimes. In addition, diet regimes during adulthood also exerted strong effects on egg production. In summary, our study provides new insight into the mate choice of C. montrouzieri as affected by seasonal changes in resources, and suggests that food availability may be a driving force in mate choice. PMID- 26269215 TI - Spontaneous breathing trial in T-tube negatively impact on autonomic modulation of heart rate compared with pressure support in critically ill patients. AB - INTRODUCTION: Spontaneous breathing with a conventional T-piece (TT) connected to the tracheal tube orotraqueal has been frequently used in clinical setting to weaning of mechanical ventilation (MV), when compared with pressure support ventilation (PSV). However, the acute effects of spontaneous breathing with TT versus PSV on autonomic function assessed through heart rate variability (HRV) have not been fully elucidated. OBJECTIVE: The purpose of this study was to examine the acute effects of spontaneous breathing in TT vs PSV in critically ill patients. METHOD: Twenty-one patients who had received MV for >= 48 h and who met the study inclusion criteria for weaning were assessed. Eligible patients were randomized to TT and PSV. Cardiorespiratory responses (respiratory rate -f, tidal volume-VT , mean blood pressure (MBP) and diastolic blood pressure (DBP), end tidal dioxide carbone (PET CO2 ), peripheral oxygen saturation (SpO2 ) and HRV indices in frequency domain (low-LF, high frequency (HF) and LF/HF ratio were evaluated. RESULTS: TT increased f (20 +/- 5 vs 25 +/- 4 breaths/min, P<0.05), MBP (90 +/- 14 vs 94 +/- 18 mmHg, P<0.05), HR (90 +/- 17 vs 96 +/- 12 beats/min, P<0.05), PET CO2 (33 +/- 8 vs 48 +/- 10 mmHg, P<0.05) and reduced SpO2 (98 +/- 1.6 vs 96 +/- 1.6%, P<0.05). In addition, LF increased (47 +/- 18 vs 38 +/- 12 nu, P<0.05) and HF reduced (29 +/- 13 vs 32 +/- 16 nu, P<0.05), resulting in higher LF/HF ratio (1.62 +/- 2 vs 1.18 +/- 1, P<0.05) during TT. Conversely, VT increased with PSV (0.58 +/- 0.16 vs 0.50 +/- 0.15 L, P<0.05) compared with TT. CONCLUSION: Acute effects of TT mode may be closely linked to cardiorespiratory mismatches and cardiac autonomic imbalance in critically ill patients. PMID- 26269216 TI - Consequences of severe obstetric complications on women's health in Morocco: please, listen to me! AB - OBJECTIVE: In Morocco, medical care for women with severe obstetric complications (near-miss cases) ends at discharge from the hospital. Little information exists regarding what happens after returning home. The aim of the study was to assess the physical and mental health consequences of near-miss events on Moroccan women 8 months after childbirth. METHODS: A prospective cohort study of 76 near-miss women was conducted in three hospitals. For every case, we recruited at least two women from the same hospital who had uncomplicated deliveries (n = 169). We used a mixed-methods approach. For the quantitative part, we analysed sociodemographic characteristics collected via a questionnaire and medical complications extracted from the medical records during a medical consultation at 8 months post-partum. Forty in-depth interviews were also conducted with 20 near-miss cases and 20 women with uncomplicated deliveries. RESULTS: The near-miss women were poorer and less educated than those who had uncomplicated deliveries. The proportion of physical consequences (serious illness) was higher among near-miss cases (22%) than uncomplicated deliveries (6%, P = 0.001). The risk of depression was significantly higher among near-miss cases with perinatal death (OR = 7.16; [95% CI: 2.85-17.98]) than among those who had an uncomplicated delivery. Interviews revealed that the economic burden of near-miss care contributed to social problems among the women and their households. CONCLUSION: A near-miss event has consequences that go beyond the first days after delivery. Developing new mechanisms for maternal and newborn health follow-up is essential and should address the mother's physical and mental health problems and involve husbands and family members. PMID- 26269217 TI - Circadian Regulation of Macronutrient Absorption. AB - Various intestinal functions exhibit circadian rhythmicity. Disruptions in these rhythms as in shift workers and transcontinental travelers are associated with intestinal discomfort. Circadian rhythms are controlled at the molecular level by core clock and clock-controlled genes. These clock genes are expressed in intestinal cells, suggesting that they might participate in the circadian regulation of intestinal functions. A major function of the intestine is nutrient absorption. Here, we will review absorption of proteins, carbohydrates, and lipids and circadian regulation of various transporters involved in their absorption. A better understanding of circadian regulation of intestinal absorption might help control several metabolic disorders and attenuate intestinal discomfort associated with disruptions in sleep-wake cycles. PMID- 26269218 TI - "Language is There to Bewilder Itself and Others": Theoretical and Clinical Contributions of Sabina Spielrein. PMID- 26269219 TI - Translational genomics for plant breeding with the genome sequence explosion. AB - The use of next-generation sequencers and advanced genotyping technologies has propelled the field of plant genomics in model crops and plants and enhanced the discovery of hidden bridges between genotypes and phenotypes. The newly generated reference sequences of unstudied minor plants can be annotated by the knowledge of model plants via translational genomics approaches. Here, we reviewed the strategies of translational genomics and suggested perspectives on the current databases of genomic resources and the database structures of translated information on the new genome. As a draft picture of phenotypic annotation, translational genomics on newly sequenced plants will provide valuable assistance for breeders and researchers who are interested in genetic studies. PMID- 26269221 TI - Inherited anomalies of innate immune receptors in pediatric-onset inflammatory diseases. AB - Pattern-recognition receptors (PRRs) can detect various pathogen-associated molecular patterns such as carbohydrates, nucleic acids or bacterial peptides and play a major role in both innate and adaptive immunity. In physiological conditions, the engagement of PRRs triggers the production of proinflammatory cytokines and promotes pathogen destruction. Inappropriate stimulation or defective regulation of PRR has been recently evidenced in several inherited inflammatory disorders. This new field of childhood-onset inflammatory diseases encompass the so-called type-I interferon-related diseases and autoinflammatory diseases. PMID- 26269220 TI - Association between in utero zidovudine exposure and nondefect adverse birth outcomes: analysis of prospectively collected data from the Antiretroviral Pregnancy Registry. AB - OBJECTIVE: To examine the association between nondefect adverse birth outcomes and in utero exposure to zidovudine (ZDV)-containing regimens versus non-ZDV antiretroviral (ARV) regimens. DESIGN: Analysis of prospectively-collected data. SETTING: Global. POPULATION: HIV-infected pregnant women prenatally exposed to antiretrovirals. METHODS: Estimation of prevalence of and risk for nondefect adverse birth outcomes among HIV-infected women. MAIN OUTCOME MEASURES: Prevalence of and risk for nondefect adverse birth outcomes. RESULTS: Among 12 780 singleton birth outcomes with in utero ZDV exposure, 96.1% were live births; 3.9% were spontaneous abortions, induced abortions or stillbirths. Among live births, 16.4% were low birthweight (LBW); 12.3% were premature. Among 1904 outcomes with in utero exposure to non-ZDV ARV regimens, 85.8% were live births; 14.2% were spontaneous abortions, induced abortions or stillbirths. Among live births, 14.1% were LBW; 12.4% were premature. Relative risk comparing exposure to ZDV-containing ARV regimens to non-ZDV ARV regimens for spontaneous abortions was 0.18 (95% confidence interval [95% CI] 0.14-0.22); induced abortions 0.28 (95% CI 0.22-0.36); stillbirths 0.76 (95% CI 0.51-1.12); premature births 1.00 (95% CI 0.87-1.15) and LBW 1.17 (95% CI 1.02-1.33). CONCLUSION: Prevalence of nondefect adverse birth outcomes is lower among outcomes with in utero ZDV exposure versus in utero non-ZDV ARV exposure. The risks for spontaneous and induced abortions were no different for ZDV-containing regimens versus non-ZDV ARV regimens. For premature births and stillbirths, there was no significant difference in risk between the two regimens. The risk of LBW was statistically significantly higher among ZDV-containing regimens versus non-ZDV ARV regimens. TWEETABLE ABSTRACT: ZDV-containing regimens do not increase the risk for nondefect adverse birth outcomes. PMID- 26269222 TI - Factors predisposing to acquired von Willebrand syndrome during the course of polycythemia vera - retrospective analysis of 142 consecutive cases. AB - INTRODUCTION: The aim of this study was to verify if PV patients with and without avWS differ in terms of their baseline clinical parameters. MATERIAL AND METHODS: The study included 142 consecutive patients with PV. avWS was diagnosed on the basis of abnormally low levels of von Willebrand factor and other routine tests. Patients with and without concomitant avWS were compared in terms of their demographic characteristics, present and past medical histories and laboratory parameters. RESULTS: Concomitant avWS was found in 17 PV patients (12.0%). Individuals with avWS have been diagnosed with PV at significantly younger age than those without, and significantly less often were in remission at the time of testing for bleeding disorders. Most of them (58.8%) presented with typical signs of bleeding disorder. Moreover, they showed significantly higher erythrocyte, leukocyte and platelet counts, abnormalities of coagulation profile corresponding to defects of primary hemostasis and abnormal values of all parameters used in the routine diagnosis of avWS. CONCLUSIONS: Even every tenth patient with PV may develop avWS. Young age at diagnosis of PV and poor response to previous treatment of this condition are potential risk factors of avWS that should be considered during history taking. Sings of bleeding disorder observed in a person with PV necessitate evaluation for avWS. PMID- 26269223 TI - Pauci-immune glomerulonephritis: does negativity of anti-neutrophilic cytoplasmic antibodies matters? AB - AIM: A significant proportion of pauci-immune glomerulonephritis (PIGN) patients are reported to have absence of anti-neutrophilic cytoplasmic antibodies (ANCA). However, studies are controversial regarding their significance and there is limited data after the new prognostic classification of PIGN. METHODS: Renal biopsy-proven cases of PIGN were included and their clinical details, ANCA status by immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA), Birmingham Vasculitis Activity Score (BVAS) and treatment outcomes at 6 months were noted. The renal biopsies were classified according to the proposed histopathological classification. Scoring was done from 0-3 for interstitial edema, interstitial fibrosis and tubular atrophy (IFTA), interstitial inflammation and arteriosclerosis. The percentage of glomeruli with sclerosis, cellular and fibrous crescents, and percentage of subjects with glomerulitis, tuft necrosis, interstitial granuloma and vasculitis were noted. RESULTS: Out of the 84 subjects included in the study, 33 (39.3%) were negative for ANCA by both IIF and ELISA. These subjects had significantly higher renal involvement, less extra-renal manifestations and lower BVAS. On histology, they had significantly higher proportion of crescentic class (66.7% vs. 41.2%, P = 0.039), higher number of cellular crescents (66.12% vs. 53.3%, P = 0.00008), higher IFTA (1.53 vs. 1.02, P = 0.009) and less interstitial edema (1.44 vs. 1.96, P = 0.003). The treatment outcomes were worse in ANCA-negative PIGN subjects, with significantly less improvement (37.2% vs. 62.8%, P = 0.02), more deterioration (40.7% vs. 14%, P = 0.006), and reduced probability of becoming dialysis free (31.6% vs. 69.6% P = 0.009). CONCLUSIONS: A negative ANCA in PIGN is associated with crescentic class, more IFTA and poor treatment outcomes. PMID- 26269224 TI - Ga(+) Basicity and Affinity Scales Based on High-Level Ab Initio Calculations. AB - The structure, relative stability and bonding of complexes formed by the interaction between Ga(+) and a large set of compounds, including hydrocarbons, aromatic systems, and oxygen-, nitrogen-, fluorine and sulfur-containing Lewis bases have been investigated through the use of the high-level composite ab initio Gaussian-4 theory. This allowed us to establish rather accurate Ga(+) cation affinity (GaCA) and Ga(+) cation basicity (GaCB) scales. The bonding analysis of the complexes under scrutiny shows that, even though one of the main ingredients of the Ga(+) -base interaction is electrostatic, it exhibits a non negligible covalent character triggered by the presence of the low-lying empty 4p orbital of Ga(+) , which favors a charge donation from occupied orbitals of the base to the metal ion. This partial covalent character, also observed in AlCA scales, is behind the dissimilarities observed when GaCA are compared with Li(+) cation affinities, where these covalent contributions are practically nonexistent. Quite unexpectedly, there are some dissimilarities between several Ga(+) -complexes and the corresponding Al(+) -analogues, mainly affecting the relative stability of pi-complexes involving aromatic compounds. PMID- 26269225 TI - Safety and feasibility of local myocardial hypothermia. AB - BACKGROUND: In ST-elevation myocardial infarction (STEMI), reduction in time to reperfusion of the occluded coronary artery reduces infarct size. In animal models, an additional reduction of infarct size was observed when hypothermia was induced before reperfusion, despite a longer ischemic time. However, several human studies did not corroborate this positive effect, which is believed to be in part due to the inability of systemic induced hypothermia to induce sufficient decrease of local myocardial temperature before reperfusion. Providing rapid local myocardial hypothermia by intracoronary infusion of saline before reperfusion in patients with STEMI may overcome this problem. In this study, we evaluate the safety and feasibility of providing rapid intracoronary myocardial hypothermia in patients undergoing intracoronary blood flow measurements based on thermodilution with continuous infusion of saline at room temperature. METHODS AND RESULTS: In 53 patients with stable angina (SA) and 20 patients with STEMI, a total of 215 measurements were performed. The measurements consisted of continuous selective intracoronary infusion of saline at room temperature with rates between 10 ml/min and 30 ml/min. Temperature changes compared to initial blood temperature (Tb ) were measured at the tip of the infusion catheter (Ti ) and distally in the coronary artery (Td ). In patients with SA, Ti was -5.65 +/- 1.41 degrees C (range -9.27 to -2.28) and Td was -0.78 +/- 0.51 degrees C (range 3.27 to -0.23 degrees C). In patients with STEMI, Ti was -7.45 +/- 0.51 degrees C (range -8.21 to -6.56) and Td was -1.37 +/- 0.82 degrees C (range -4.62 to -0.74 degrees C). In all patients, steady-state intracoronary hypothermia was achieved within 15 sec and could be maintained without noticeable complications. CONCLUSION: This study demonstrates the safety and feasibility of inducing intracoronary hypothermia by selective infusion of saline at room temperature in patients with SA and STEMI. Steady-state hypothermia could be achieved and maintained quickly, easily, and safely using common PCI techniques. Therefore, our findings warrant further studies to the use of intracoronary hypothermia to enhance myocardial salvage in acute myocardial infarction. PMID- 26269226 TI - Adult neural progenitor cells from Huntington's disease mouse brain exhibit increased proliferation and migration due to enhanced calcium and ROS signals. AB - OBJECTIVES: Huntington's disease (HD) is an inherited human neurodegenerative disorder characterized by uncontrollable movement, psychiatric disturbance and cognitive decline. Impaired proliferative/differentiational potentials of adult neural progenitor cells (ANPCs) have been thought to be a pathogenic mechanism involved in it. In this study, we aimed to elucidate intrinsic properties of ANPCs subjected to neurodegenerative condition in YAC128 HD mice. MATERIALS AND METHODS: ANPCs were isolated from the SVZ regions of 4-month-old WT and YAC128 mice. Cell proliferation, migration and neuronal differentiation in vitro were compared between these two genotypes with/without Ca(2+) inhibitors or ROS scavenger treatments. Differences in ANPC proliferation and differentiation capabilities in vivo between the two genotypes were evaluated using Ki-67 and Doublecortin (DCX) immunofluorescence respectively. RESULTS: Compared to WT ANPCs, YAC128 ANPCs had significantly enhanced cell proliferation, migration and neuronal differentiation in vitro, accompanied by increased Ca(2+) and ROS signals. Raised proliferation and migration in YAC128 ANPCs were abolished by Ca(2+) signalling antagonists and ROS scavenging. However, in vivo, HD ANPCs failed to show any elevated proliferation or differentiation. CONCLUSIONS: Increased Ca(2+) signalling and higher level of ROS conferred HD ANPC enhancement of proliferation and migration potentials. However, the in vivo micro-environment did not support endogenous ANPCs to respond appropriately to neuronal loss in these YAC128 mouse brains. PMID- 26269227 TI - Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage. AB - Multiple cannabinoids derived from the marijuana plant have potential therapeutic benefits but most have not been well investigated, despite the widespread legalization of medical marijuana in the USA and other countries. Therapeutic indications will depend on determinations as to which of the multiple cannabinoids, and other biologically active chemicals that are present in the marijuana plant, can be developed to treat specific symptoms and/or diseases. Such insights are particularly critical for addiction disorders, where different phytocannabinoids appear to induce opposing actions that can confound the development of treatment interventions. Whereas Delta(9)-tetracannabinol has been well documented to be rewarding and to enhance sensitivity to other drugs, cannabidiol (CBD), in contrast, appears to have low reinforcing properties with limited abuse potential and to inhibit drug-seeking behavior. Other considerations such as CBD's anxiolytic properties and minimal adverse side effects also support its potential viability as a treatment option for a variety of symptoms associated with drug addiction. However, significant research is still needed as CBD investigations published to date primarily relate to its effects on opioid drugs, and CBD's efficacy at different phases of the abuse cycle for different classes of addictive substances remain largely understudied. Our paper provides an overview of preclinical animal and human clinical investigations, and presents preliminary clinical data that collectively sets a strong foundation in support of the further exploration of CBD as a therapeutic intervention against opioid relapse. As the legal landscape for medical marijuana unfolds, it is important to distinguish it from "medical CBD" and other specific cannabinoids, that can more appropriately be used to maximize the medicinal potential of the marijuana plant. PMID- 26269230 TI - How body torque and Strouhal number change with swimming speed and developmental stage in larval zebrafish. AB - Small undulatory swimmers such as larval zebrafish experience both inertial and viscous forces, the relative importance of which is indicated by the Reynolds number (Re). Re is proportional to swimming speed (vswim) and body length; faster swimming reduces the relative effect of viscous forces. Compared with adults, larval fish experience relatively high (mainly viscous) drag during cyclic swimming. To enhance thrust to an equally high level, they must employ a high product of tail-beat frequency and (peak-to-peak) amplitude fAtail, resulting in a relatively high fAtail/vswim ratio (Strouhal number, St), and implying relatively high lateral momentum shedding and low propulsive efficiency. Using kinematic and inverse-dynamics analyses, we studied cyclic swimming of larval zebrafish aged 2-5 days post-fertilization (dpf). Larvae at 4-5 dpf reach higher f (95 Hz) and Atail (2.4 mm) than at 2 dpf (80 Hz, 1.8 mm), increasing swimming speed and Re, indicating increasing muscle powers. As Re increases (60 -> 1400), St (2.5 -> 0.72) decreases nonlinearly towards values of large swimmers (0.2 0.6), indicating increased propulsive efficiency with vswim and age. Swimming at high St is associated with high-amplitude body torques and rotations. Low propulsive efficiencies and large yawing amplitudes are unavoidable physical constraints for small undulatory swimmers. PMID- 26269228 TI - Safety and Toxicology of Cannabinoids. AB - There is extensive research on the safety, toxicology, potency, and therapeutic potential of cannabis. However, uncertainty remains facilitating continued debate on medical and recreational cannabis policies at the state and federal levels. This review will include a brief description of cannabinoids and the endocannabinoid system; a summary of the acute and long-term effects of cannabis; and a discussion of the therapeutic potential of cannabis. The conclusions about safety and efficacy will then be compared with the current social and political climate to suggest future policy directions and general guidelines. PMID- 26269231 TI - 'Super' or just 'above average'? Supershedders and the transmission of Escherichia coli O157:H7 among feedlot cattle. AB - Supershedders have been suggested to be major drivers of transmission of Escherichia coli O157:H7 (E. coli O157:H7) among cattle in feedlot environments, despite our relatively limited knowledge of the processes that govern periods of high shedding within an individual animal. In this study, we attempt a data driven approach, estimating the key characteristics of high shedding behaviour, including effects on transmission to other animals, directly from a study of natural E. coli O157:H7 infection of cattle in a research feedlot, in order to develop an evidence-based definition of supershedding. In contrast to the hypothesized role of supershedders, we found that high shedding individuals only modestly increased the risk of transmission: individuals shedding over 10(3) cfu g(-1) faeces were estimated to pose a risk of transmission only 2.45 times greater than those shedding below that level. The data suggested that shedding above 10(3) cfu g(-1) faeces was the most appropriate definition of supershedding behaviour and under this definition supershedding was surprisingly common, with an estimated prevalence of 31.3% in colonized individuals. We found no evidence that environmental contamination by faeces of shedding cattle contributed to transmission over timescales longer than 3 days and preliminary evidence that higher stocking density increased the risk of transmission. PMID- 26269232 TI - Influence of physico-chemical, mechanical and morphological fingerpad properties on the frictional distinction of sticky/slippery surfaces. AB - This study investigates how the fingerpad hydrolipid film, shape, roughness and rigidity influence the friction when it rubs surfaces situated in the slippery psychophysical dimension. The studied counterparts comprised two 'real' (physical) surfaces and two 'virtual' surfaces. The latter were simulated with a tactile stimulator named STIMTAC. Thirteen women and 13 men rubbed their right forefingers against the different surfaces as their arms were displaced by a DC motor providing constant velocity and sliding distance. Tangential and normal forces were measured with a specific tribometer. The fingerpad hydrolipid film was characterized by Fourier transform infrared spectroscopy. The shape and roughness of fingers were extrapolated from replicas. Indentation measurements were carried out to determine fingerpad effective elastic modulus. A clear difference was observed between women and men in terms of friction behaviour. The concept of tactile frictional contrast (TFC) which was introduced quantifies an individual's propensity to distinguish two surfaces frictionally. The lipids/water ratio and water amount on the finger skin significantly influenced the TFC. A correlation was observed between the TFC and fingerpad roughness, i.e. the height of the fingerpad ridges. This is essentially owing to gender differences. A significant difference between men's and women's finger topography was also noted, because our results suggested that men have rougher fingers than women. The friction measurements did not correlate with the fingerpad curvature nor with the epidermal ridges' spatial period. PMID- 26269234 TI - How similar can co-occurring species be in the presence of competition and ecological drift? AB - If two species live on a single resource, the one with a slight advantage will out-compete the other: complete competitors cannot coexist. This is known as the competitive exclusion principle. If no extinction occurs, it is because evolutionary adaptation to slightly different niches takes place. Therefore, it is widely accepted that ecological communities are assembled by evolutionary differentiation and progressive adaptation of species to different niches. However, some ecologists have recently challenged this classic paradigm highlighting the importance of chance and stochasticity. Using a synthetic framework for community dynamics, here we show that, while deterministic descriptors predict coexistence, species similarity is limited in a more restrictive way in the presence of stochasticity. We analyse the stochastic extinction phenomenon, showing that extinction occurs as competitive overlap increases above a certain threshold well below its deterministic counterpart. We also prove that the extinction threshold cannot be ascribed only to demographic fluctuations around small population sizes. The more restrictive limit to species similarity is, therefore, a consequence of the complex interplay between competitive interactions and ecological drift. As a practical implication, we show that the existence of a stochastic limit to similarity has important consequences in the recovery of fragmented habitats. PMID- 26269233 TI - Novel nanocomposite biomaterials with controlled copper/calcium release capability for bone tissue engineering multifunctional scaffolds. AB - This work aimed to develop novel composite biomaterials for bone tissue engineering (BTE) made of bioactive glass nanoparticles (Nbg) and alginate cross linked with Cu(2+) or Ca(2+) (AlgNbgCu, AlgNbgCa, respectively). Two-dimensional scaffolds were prepared and the nanocomposite biomaterials were characterized in terms of morphology, mechanical strength, bioactivity, biodegradability, swelling capacity, release profile of the cross-linking cations and angiogenic properties. It was found that both Cu(2+) and Ca(2+) are released in a controlled and sustained manner with no burst release observed. Finally, in vitro results indicated that the bioactive ions released from both nanocomposite biomaterials were able to stimulate the differentiation of rat bone marrow-derived mesenchymal stem cells towards the osteogenic lineage. In addition, the typical endothelial cell property of forming tubes in Matrigel was observed for human umbilical vein endothelial cells when in contact with the novel biomaterials, particularly AlgNbgCu, which indicates their angiogenic properties. Hence, novel nanocomposite biomaterials made of Nbg and alginate cross-linked with Cu(2+) or Ca(2+) were developed with potential applications for preparation of multifunctional scaffolds for BTE. PMID- 26269235 TI - Growth Responses of Juvenile Red Drum Sciaenops ocellatus to Dietary Phenylalanine and Tyrosine Can Be Used to Calculate the Total Aromatic Amino Acid Requirement. AB - BACKGROUND: A current priority in aquaculture is the replacement of fish meal with alternative feedstuffs to ensure the industry's sustainability. However, most alternative protein sources are deficient in at least 1 indispensable amino acid (IAA). Therefore, there is a critical need to establish refined estimates of IAA requirements of fish. OBJECTIVES: The objectives of this study were to determine the total aromatic amino acid (TAAA) requirement (Phe + Tyr) and the Tyr replacement value for Phe in juvenile red drum Sciaenops ocellatus. METHODS: The TAAA requirement was obtained by feeding juvenile red drum diets that contained incremental amounts of Phe (0.54, 0.84, 1.14, 1.44, 1.74, and 2.04 g/100 g dry diet) and a fixed concentration of Tyr. Because of the TAAA requirement obtained, a second feeding trial was conducted to determine the maximum Tyr replacement value for Phe when a control diet was prepared with an 80%:20% Phe-to-Tyr ratio (Phe:Tyr; 1.60 g Phe/100 g dry diet and 0.41 g Tyr/100 g), and 5 experimental diets were prepared by decreasing the inclusion of Phe and increasing the inclusion of Tyr (Phe:Tyr of 70%:30%, 60%:40%, 50%:50%, 40%:60%, and 30%:70%). RESULTS: Weight gain, the feed efficiency ratio, and the protein efficiency ratio increased 354%, 133%, and 134%, respectively, relative to that of fish fed the basal diet as the Phe concentration increased to 1.44 g/100 g of dry diet; at higher concentrations of Phe, no significant differences were found between treatments. Analysis of the weight gain data with a broken-line model estimated the TAAA requirement of red drum to be 2.10 g/100 g dry diet (1.69 g Phe + 0.41 g Tyr). The maximum Tyr replacement value for Phe was estimated at 40%:60% Phe:Tyr, because only fish fed the diet with a 30%:70% Phe:Tyr ratio had a significant reduction (42%) in growth performance. CONCLUSION: The TAAA requirement for maximum growth of juvenile red drum was estimated to be 2.10 +/- 0.08 g/100 g dry diet. Moreover, Tyr can account for up to 60% of the TAAA requirement of juvenile red drum. PMID- 26269236 TI - Dietary Lipids Inform the Gut and Brain about Meal Arrival via CD36-Mediated Signal Transduction. AB - Sensing mechanisms for nutrients, in particular dietary fat, operate in the mouth, brain, and gastrointestinal tract and play a key role in regulating feeding behavior and energy balance. Critical to these regulatory mechanisms are the specialized receptors present on taste buds on the tongue, on neurons in specialized centers in the brain, and on epithelial and enteroendocrine cells in the intestinal mucosa. These receptors recognize nutrients and respond by inducing intracellular signals that trigger release of bioactive compounds that influence other organs and help coordinate the response to the meal. Components of dietary fat that are recognized by these receptors are the long-chain fatty acids that act as ligands for 2 G protein-coupled receptors, GPR40 and GPR120, and the fatty acid (FA) translocase/CD36. Recent evidence that emphasizes the important role of CD36 in orosensory, intestinal, and neuronal sensing of FAs under physiologic conditions is highlighted in the review. How this role intersects with that of GPR120 and GPR40 in the regulation of food preference and energy balance is briefly discussed. PMID- 26269237 TI - Participation in the Juntos Conditional Cash Transfer Program in Peru Is Associated with Changes in Child Anthropometric Status but Not Language Development or School Achievement. AB - BACKGROUND: It is unclear what effects a conditional cash transfer (CCT) program would have on child anthropometry, language development, or school achievement in the context of the nutrition transition experienced by many low- and middle income countries. OBJECTIVE: We estimated the association of participation in Peru's Juntos CCT with anthropometry, language development, and school achievement among children aged 7-8 y. METHODS: We used data from the Young Lives Study of a cohort born between 2001 and 2002. We estimated associations of the Juntos program with height-for-age z score (HAZ), body mass index-for-age z score (BAZ), stunting, and overweight at age 7-8 y separately for children participating in the program for >=2 y (n = 169) and children participating for <2 y (n = 188). We then estimated associations with receptive vocabulary and grade achievement among children who had been assessed at age 4-6 y before enrollment in Juntos (n = 243). We identified control subjects using propensity score matching and conducted difference-in-differences comparisons. RESULTS: Juntos participation was associated with increases in HAZ among boys participating for >=2 y [average effect of treatment among the treated (ATT): 0.43; 95% CI: 0.09, 0.77; P = 0.01] and for boys participating for <2 y (ATT: 0.52; 95% CI: 0.23, 0.80; P < 0.01). Among girls participating in the program for >=2 y, BAZ declined (ATT: -0.60; 95% CI: -1.00, -0.21; P < 0.01) as did the prevalence of overweight (ATT: -22.0 percentage points; 95% CI: -42.5, -2.7 percentage points; P = 0.03). We observed no significant associations of Juntos participation with receptive vocabulary or grade attainment. CONCLUSIONS: CCT program participation in Peru was associated with better linear growth among boys and decreased BAZ among girls, highlighting that a large-scale poverty alleviation intervention may influence anthropometric outcomes in the context of the nutrition transition. PMID- 26269239 TI - Dietary Almonds Increase Serum HDL Cholesterol in Coronary Artery Disease Patients in a Randomized Controlled Trial. AB - BACKGROUND: More than one-half of coronary artery disease (CAD) patients have low HDL cholesterol despite having well-managed LDL cholesterol. Almond supplementation has not been shown to elevate circulating HDL cholesterol concentrations in clinical trials, perhaps because the baseline HDL cholesterol of trial subjects was not low. OBJECTIVE: This clinical trial was designed to test the effect of almond supplementation on low HDL cholesterol in CAD patients. METHODS: A total of 150 CAD patients (50 per group), with serum LDL cholesterol <=100 mg/dL and HDL cholesterol <=40 mg/dL in men and <=50 mg/dL in women, were recruited from the Aga Khan University Hospital. After recording vital signs and completing a dietary and physical activity questionnaire, patients were randomly assigned to 1 of the following 3 groups: the no-intervention group (NI), the Pakistani almonds group (PA), and the American almonds group (AA). The respective almond varieties (10 g/d) were given to patients with instructions to soak them overnight, remove the skin, and eat them before breakfast. Blood samples for lipid profiling, body weight, and blood pressure were collected, and assessment of dietary patterns was done at baseline, week 6, and week 12. RESULTS: Almonds significantly increased HDL cholesterol. At weeks 6 and 12, HDL cholesterol was 12-14% and 14-16% higher, respectively, in the PA and AA than their respective baselines. In line with previous reports, serum concentrations of total cholesterol, triglycerides, LDL cholesterol, and VLDL cholesterol; total-to-HDL and LDL-to-HDL cholesterol ratios, and the atherogenic index were reduced in both the PA and AA at weeks 6 and 12 compared with baseline (P < 0.05). Effects on serum lipids did not differ between the 2 almond groups. Dietary patterns, body weight, and blood pressure did not change in any of the 3 groups during the trial. CONCLUSION: A low dose of almonds (10 g/d) consumed before breakfast can increase HDL cholesterol, in addition to improving other markers of abnormal lipid metabolism in CAD patients with low initial HDL cholesterol. This trial was registered at the Australian New Zealand Clinical Trial Registry as ACTRN12614000036617. PMID- 26269238 TI - Higher Intake of PUFAs Is Associated with Lower Total and Visceral Adiposity and Higher Lean Mass in a Racially Diverse Sample of Children. AB - BACKGROUND: Polyunsaturated fatty acids (PUFAs) are associated with protection from obesity-related phenotypes in adults; however, the relation between reported intake of PUFAs with body-composition outcomes in children remains unknown. OBJECTIVE: Our objective was to examine how self-reported intakes of PUFAs, including total, n-6 (omega-6), and n-3 (omega-3) PUFAs and ratios of n-6 to n-3 PUFAs and PUFAs to saturated fatty acids (SFAs), are associated with measures of adiposity and lean mass (LM) in children. We hypothesized that higher self reported intakes of PUFAs and the ratio of PUFAs to SFAs would be positively associated with LM and negatively associated with total adiposity. METHODS: Body composition and dietary intake were measured in a racially diverse sample of 311 children (39% European American, 34% African American, and 27% Hispanic American) aged 7-12 y. Body composition and abdominal fat distribution were measured by dual-energy X-ray absorptiometry and computed tomography scans, respectively. Self-reported dietary intakes (including total PUFAs, n-3 PUFAs, n-6 PUFAs, and SFAs) were assessed by using two 24-h recalls. Independent-sample t tests and multiple linear regression analyses were conducted. RESULTS: Total PUFA intake was positively associated with LM (P = 0.049) and negatively associated with percentage of body fat (%BF; P = 0.033) and intra-abdominal adipose tissue (IAAT; P = 0.022). A higher ratio of PUFAs to SFAs was associated with higher LM (P = 0.030) and lower %BF (P = 0.028) and IAAT (P = 0.048). Intakes of n-3 and n-6 PUFAs were positively associated with LM (P = 0.017 and P = 0.021, respectively), and the ratio of n-6 to n-3 PUFAs was negatively associated with IAAT (P = 0.014). All results were independent of biological, environmental, and genetic covariates. CONCLUSIONS: Our results show that a higher self-reported intake of PUFAs and a higher ratio of PUFAs to SFAs are positively associated with LM and negatively associated with visceral adiposity and %BF in a healthy cohort of racially diverse children aged 7-12 y. This trial was registered at clinicaltrials.gov as NCT00726778. PMID- 26269241 TI - Breakfasts Higher in Protein Increase Postprandial Energy Expenditure, Increase Fat Oxidation, and Reduce Hunger in Overweight Children from 8 to 12 Years of Age. AB - BACKGROUND: Currently 1 in every 3 children aged 2-19 y is overweight or obese. Breakfast is a key component of a healthy diet and has the potential to affect children's health. OBJECTIVE: The objective of this study was to determine whether consumption of a protein-based breakfast (PRO) increases postprandial energy metabolism and substrate oxidation, reduces hunger, and reduces food intake at lunch compared with a carbohydrate-based breakfast (CHO) in normal weight (NW) vs. overweight/obese (OW) children. METHODS: A randomized, crossover design study was conducted in NW (n = 16; 33 +/- 1 kg) and OW (n = 13; 46 +/- 2 kg) children (10 +/- 1 y). Participants were served either a PRO [344 kcal, 21% protein (18 g), 52% carbohydrate, and 27% fat] or CHO [327 kcal, 4% protein (3 g), 67% carbohydrate, and 29% fat]. Energy expenditure (EE), substrate oxidation, appetite, and blood glucose were measured over a 4 h period. Four hour postprandial participants were provided with access to a lunch buffet and food intake was recorded. RESULTS: After breakfast, OW children in the PRO group had higher (P < 0.0001) EEs and fat oxidation over the 4 h period than did the NW children in the CHO and PRO groups. There was no difference in postprandial EE or carbohydrate oxidation between the CHO and PRO groups over the 4 h period; however, fat oxidation was 16% higher (P < 0.05) after the PRO than the CHO and postprandial carbohydrate oxidation at 4 h was 32% higher after the PRO than the CHO (P < 0.01), independent of weight group. All participants had decreased feelings of hunger (-14%; P < 0.01) and increased fullness (+32%; P < 0.05) after the PRO than the CHO. Finally, there was no difference in food intake within the NW and OW groups. CONCLUSION: This study indicates that breakfast macronutrient composition affects postprandial responses in both NW and OW children. A PRO increases postprandial EE and fat oxidation, reduces hunger, and increases satiety when compared with a carbohydrate-based breakfast. PMID- 26269240 TI - Plasma Selenium Concentrations Are Sufficient and Associated with Protease Inhibitor Use in Treated HIV-Infected Adults. AB - BACKGROUND: Selenium is an essential constituent of selenoproteins, which play a substantial role in antioxidant defense and inflammatory cascades. Selenium deficiency is associated with disease states characterized by inflammation, including cardiovascular disease (CVD). Although HIV infection has been associated with low selenium, the role of selenium status in HIV-related CVD is unclear. OBJECTIVES: We sought to assess associations between plasma selenium and markers of inflammation, immune activation, and subclinical vascular disease in HIV-infected adults on contemporary antiretroviral therapy (ART) and to determine if statin therapy modifies selenium status. METHODS: In the Stopping Atherosclerosis and Treating Unhealthy bone with RosuvastatiN trial, HIV-infected adults on stable ART were randomly assigned 1:1 to rosuvastatin or placebo. Plasma selenium concentrations were determined at entry, week 24, and week 48. Spearman correlation and linear regression analyses were used to assess relations between baseline selenium, HIV-related factors and markers of inflammation, immune activation, and subclinical vascular disease. Changes in selenium over 24 and 48 wk were compared between groups. RESULTS: One hundred forty-seven HIV infected adults were included. All participants were on ART. Median current CD4+ count was 613, and 76% had HIV-1 RNA <=48 copies/mL (range: <20-600). Median plasma selenium concentration was 122 MUg/L (range: 62-200). At baseline, higher selenium was associated with protease inhibitor (PI) use, lower body mass index, and a higher proportion of activated CD8+ T cells (CD8+CD38+human leukocyte antigen-DR+), but not markers of inflammation or subclinical vascular disease. Over 48 wk, selenium concentrations increased in the statin group (P < 0.01 within group), but the change did not differ between groups (+13.1 vs. +5.3 MUg/L; P = 0.14 between groups). CONCLUSIONS: Plasma selenium concentrations were within the normal range for the background population and were not associated with subclinical vascular disease in HIV-infected adults on contemporary ART. The association between current PI use and higher selenium may have implications for ART allocation, especially in resource-limited countries. Also, it appears that statin therapy may increase selenium concentrations; however, larger studies are necessary to confirm this finding. This trial was registered at clinicaltrials.gov as NCT01218802. PMID- 26269243 TI - The Intestinal Transport of Bovine Milk Exosomes Is Mediated by Endocytosis in Human Colon Carcinoma Caco-2 Cells and Rat Small Intestinal IEC-6 Cells. AB - BACKGROUND: MicroRNAs play essential roles in gene regulation. A substantial fraction of microRNAs in tissues and body fluids is encapsulated in exosomes, thereby conferring protection against degradation and a pathway for intestinal transport. MicroRNAs in cow milk are bioavailable in humans. OBJECTIVE: This research assessed the transport mechanism of bovine milk exosomes, and therefore microRNAs, in human and rodent intestinal cells. METHODS: The intestinal transport of bovine milk exosomes and microRNAs was assessed using fluorophore labeled bovine milk exosomes in human colon carcinoma Caco-2 cells and rat small intestinal IEC-6 cells. Transport kinetics and mechanisms were characterized using dose-response studies, inhibitors of vesicle transport, carbohydrate competitors, proteolysis of surface proteins on cells and exosomes, and transepithelial transport in transwell plates. RESULTS: Exosome transport exhibited saturation kinetics at 37 degrees C [Michaelis constant (Km) = 55.5 +/- 48.6 MUg exosomal protein/200 MUL of media; maximal transport rate = 0.083 +/- 0.057 ng of exosomal protein . 81,750 cells(-1) . h(-1)] and decreased by 64% when transport was measured at 4 degrees C, consistent with carrier-mediated transport in Caco-2 cells. Exosome uptake decreased by 61-85% under the following conditions compared with controls in Caco-2 cells: removal of exosome and cell surface proteins by proteinase K, inhibition of endocytosis and vesicle trafficking by synthetic inhibitors, and inhibition of glycoprotein binding by carbohydrate competitors. When milk exosomes, at a concentration of 5 times the Km, were added to the upper chamber in transwell plates, Caco-2 cells accumulated miR-29b and miR-200c in the lower chamber, and reverse transport was minor. Transport characteristics were similar in IEC-6 cells and Caco-2 cells, except that substrate affinity and transporter capacity were lower and higher, respectively. CONCLUSION: The uptake of bovine milk exosomes is mediated by endocytosis and depends on cell and exosome surface glycoproteins in human and rat intestinal cells. PMID- 26269244 TI - Identification of mutations in U2HR in two Chinese families with Marie Unna hereditary hypotrichosis. AB - Marie Unna hereditary hypotrichosis (MUHH) is a rare autosomal dominant genodermatosis characterized by coarse, wiry, twisted hair developing during early childhood, with subsequent progressive hair loss. Recently, mutations in U2HR, an inhibitory upstream open reading frame in the 5' untranslated region of the human hairless gene (HR), were identified as the underlying cause of MUHH. We investigated two unrelated Chinese multigenerational families with MUHH. By sequencing U2HR in the two families, we identified two previously reported mutations, c.1A >T (p.Met1?) and c.104A>G (p*35Wext1263*). Both these mutations cosegregated with the disease phenotype in the two families. PMID- 26269242 TI - The Dihydrofolate Reductase 19 bp Polymorphism Is Not Associated with Biomarkers of Folate Status in Healthy Young Adults, Irrespective of Folic Acid Intake. AB - BACKGROUND: Dihydrofolate reductase (DHFR) is essential for the conversion of folic acid to active folate needed for one-carbon metabolism. Common genetic variation within DHFR is restricted to the noncoding regions, and previous studies have focused on a 19 bp deletion/insertion polymorphism (rs70991108) within intron 1. Reports of an association between this polymorphism and blood folate biomarker concentrations are conflicting. OBJECTIVE: In this study, we evaluated whether the DHFR 19 bp deletion/insertion polymorphism affects circulating folate biomarkers in, to our knowledge, the largest cohort to address this question to date. METHODS: Healthy young Irish individuals (n = 2507) between 19 and 36 y of age were recruited between February 2003 and February 2004. Folic acid intake from supplements and fortified foods was assessed with the use of a customized food intake questionnaire. Concentrations of serum folate and vitamin B-12, red blood cell (RBC) folate, and plasma total homocysteine (tHcy) were measured. Data were analyzed with the use of linear regression models. RESULTS: Folic acid intake was positively associated with serum (P < 0.0001) and RBC (P = 0.0005) folate concentration and was inversely associated with plasma tHcy (P = 0.001) as expected. The DHFR 19 bp polymorphism was not significantly associated with either serum (P = 0.82) or RBC (P = 0.21) folate, or plasma tHcy (P = 0.20), even in those within the highest quintile of folic acid intake (>326 MUg folic acid/d; P = 0.96). A nonsignificant trend toward lower RBC folate by genotype (P = 0.09) was observed in the lowest folic acid intake quintile (0-51 MUg/d). CONCLUSION: In this cohort of healthy young individuals, the DHFR 19 bp deletion allele did not significantly affect circulating folate status, irrespective of folic acid intake. Our data rule out a strong functional effect from this polymorphism on blood folate concentrations. PMID- 26269245 TI - Deciphering the microbiology of hidradenitis suppurativa: a step forward towards understanding an enigmatic inflammatory skin disease. PMID- 26269246 TI - Being Accountable or Filling in Forms: Managers and Clinicians' Views About Communicating Risk. AB - PURPOSE: Assessment, documentation, and prevention of risk are central to mental health services. However, there is a paucity of research examining how risk is perceived by key stakeholders including managers and clinicians. DESIGN AND METHODS: Qualitative, exploratory design. In-depth interviews were held with 22 senior managers and 21 clinicians. FINDINGS: Communicating risk was a major theme to emerge. For managers, accountability was a primary consideration in communicating risk and therefore influential over nursing practice. Clinicians were more likely to view the organizational processes of communicating risk as a bureaucratic exercise. PRACTICE IMPLICATIONS: The significant difference between managers and clinicians is problematic for achieving consumer-focused mental health service delivery, a more critical approach to risk is essential in preserving the therapeutic relationship. PMID- 26269247 TI - Introduction of the RTA-Bddsx gene induces female-specific lethal effects in transformed Bactrocera dorsalis (Hendel). AB - BACKGROUND: The oriental fruit fly, Bactrocera dorsalis (Hendel), can reduce fruit production and quality and is considered to be a major insect pest in many Asian countries. A system combining the toxicity of ricin and the alternative RNA splicing properties of doublesex (RTA-Bddsx) has been proposed that results in differential sexual processing in vitro. A transgenic approach was used in this study to confirm the existence of female-specific lethal effects in vivo. RESULTS: The piggyBac-based vector PB-Acp-CF21-26, which carries the actin 5C promoter and RTA-Bddsx, was used to establish transgenic lines. Five surviving male flies (F1) demonstrated the presence of selection marker Ds-Red((+)) throughout their entire bodies following single-pair mating with wild-type females, indicating germline transmission. A high percentage of males (59.6-100%) were observed in transformed F3 offspring, and this skewed sex ratio indicated that the female-lethal effects of the RTA-Bddsx system were heritable and functioned well in B. dorsalis. Some transformed female flies were observed, and these unexpected results were attributed to the loss of the intact transgene after genomic PCR analyses. CONCLUSION: This transgenic study provides direct evidence for the female-specific lethal effects of RTA-Bddsx in B. dorsalis and offers a novel and promising approach for the control of B. dorsalis in the future. (c) 2015 Society of Chemical Industry. PMID- 26269249 TI - Further delineation of the KBG syndrome caused by ANKRD11 aberrations. PMID- 26269248 TI - Next-generation sequencing-based genome diagnostics across clinical genetics centers: implementation choices and their effects. PMID- 26269250 TI - Salvage STA-MCA bypass surgery in an adult moyamoya patient after failed indirect revascularization surgery. AB - A 39-year-old female moyamoya disease patient underwent a salvage direct bypass surgery involving anastomosis of the superficial temporal artery or STA and middle cerebral artery or MCA. This report describes a rare case of moyamoya disease that was revascularized after the previous indirect bypass surgery failed to restore collateral blood flow. PMID- 26269251 TI - Re to the letter: Adult idiopatic occlusion of Monro foramina: Intraoperative endoscopic reinterpretation of radiological data and review of the literature. PMID- 26269252 TI - Dyschromatosis Universalis Hereditaria with Oral Leukokeratosis--A Case of Mistaken Identity and Review of the Literature. AB - Dyschromatosis universalis hereditaria (DUH) is a rare pigmentary genodermatosis characterized by reticulated hyper- and hypopigmented macules distributed over the trunk and extremities in otherwise healthy patients. DUH presents in a fashion similar to that of a variety of reticulate and pigmentary dermatoses, some of which are associated with precancerous entities and other comorbidities. It is therefore imperative that the clinician recognize and differentiate these disorders so that appropriate screening and counseling can be offered to the patient. We report a case of DUH in a 13-year-old boy presenting with oral leukokeratosis, with a review of the literature exploring the differential diagnoses. PMID- 26269253 TI - Fabrication of Straight Silicon Nanowires and Their Conductive Properties. AB - Straight Si nanowires (Si NWs) with tens to hundreds of micrometers in length and 40-200 nm in diameter are achieved by annealing a Si substrate coated with metallic Fe. The influences of annealing gas and temperature on the formation of Si NWs are investigated. It is found that the annealing gas has significant impacts on the microstructure of the NWs. By increasing the hydrogen ratio in the forming gas, straight and crystal Si NWs with thin oxide shells are obtained. Both the conductive properties along and perpendicular to the NW are investigated by conductive atomic force microscopy (CAFM) on single NWs. The conductance perpendicular to the NW is too poor to be detected, while a weak conductance can be measured along the NW. The results indicate that the measured resistance mainly comes from the contact(s), and the Si NWs exhibit typical semiconductive conductance themselves, which should have potential applications in nanoelectronics. PMID- 26269255 TI - Mortality related to candidemia and risk factors associated with non-Candida albicans. PMID- 26269254 TI - Toxicological effect of TiO2 nanoparticle-induced myocarditis in mice. AB - Currently, impacts of exposure to TiO2 nanoparticles (NPs) on the cardiovascular system are not well understood. The aim of this study was to investigate whether TiO2 NPs induce myocarditis and its underlying molecular mechanism in the cardiac inflammation in mice. Mice were exposed to TiO2 NPs for 6 months; biochemical parameters of serum and expression of Th1-related and Th2-related cytokines in the heart were investigated. The results showed that TiO2 NP exposure resulted in cardiac lesions coupling with pulmonary inflammation; increases of aspartate aminotransferase (AST), creatine kinase (CK), C-reaction protein (CRP), lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBDH), adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein-1 (MCP-1) levels; and a reduction of nitric oxide (NOx) level in the serum. These were associated with increases of nuclear factor-kappaB (NF-kappaB), tumor necrosis factor-alpha (TNF alpha), interleukin (IL)-4, IL-6, transforming growth factor-beta (TGF-beta), creatine kinase, CRP, adhesion molecule-1, and monocyte chemoattractant protein 1, interferon-gamma (IFN-gamma), signal transducers and activators of transcription (STAT)1, STAT3, or STAT6, GATA-binding domain-3, GATA-binding domain-4, endothelin-1 expression levels, and T-box expressed in T cells expression level that is the master regulator of pro-inflammatory cytokines and transcription factors in the heart. These findings imply that TiO2 NP exposure may increase the occurrence and development of cardiovascular diseases. PMID- 26269256 TI - Cartilage oligomeric matrix protein: a new promising biomarker of liver fibrosis in chronic hepatitis C. AB - Cartilage oligomeric matrix protein (COMP) is a biomarker of fibrosis in lung and skin. In this exploratory study we investigated the biomarker potential of COMP in chronic hepatitis C (CHC). We included consecutive patients with CHC admitted to the Department of Infectious Diseases, Lund University Hospital. COMP was analysed in serum using ELISA. The correlations between COMP and liver fibrosis, determined by transient elastography (TE) (n = 47) and liver biopsy (n = 28) were assessed. We also studied COMP prospectively in relation to antiviral treatment (n = 10). COMP correlated with the degree of liver fibrosis as assessed by TE (r = 0.71, p < 0.001) and liver biopsy (rs = 0.65, p < 0.001). After successful treatment of CHC, COMP decreased from 18 to 13 U/l (p = 0.011). We suggest that COMP is associated with the stage of liver fibrosis in CHC. The biomarker potential of COMP in CHC warrants further investigation. PMID- 26269258 TI - Risk Preferences, Probability Weighting, and Strategy Tradeoffs in Wildfire Management. AB - Wildfires present a complex applied risk management environment, but relatively little attention has been paid to behavioral and cognitive responses to risk among public agency wildfire managers. This study investigates responses to risk, including probability weighting and risk aversion, in a wildfire management context using a survey-based experiment administered to federal wildfire managers. Respondents were presented with a multiattribute lottery-choice experiment where each lottery is defined by three outcome attributes: expenditures for fire suppression, damage to private property, and exposure of firefighters to the risk of aviation-related fatalities. Respondents choose one of two strategies, each of which includes "good" (low cost/low damage) and "bad" (high cost/high damage) outcomes that occur with varying probabilities. The choice task also incorporates an information framing experiment to test whether information about fatality risk to firefighters alters managers' responses to risk. Results suggest that managers exhibit risk aversion and nonlinear probability weighting, which can result in choices that do not minimize expected expenditures, property damage, or firefighter exposure. Information framing tends to result in choices that reduce the risk of aviation fatalities, but exacerbates nonlinear probability weighting. PMID- 26269257 TI - IL-21-mediated non-canonical pathway for IL-1beta production in conventional dendritic cells. AB - The canonical pathway for IL-1beta production requires TLR-mediated NF-kappaB dependent Il1b gene induction, followed by caspase-containing inflammasome mediated processing of pro-IL-1beta. Here we show that IL-21 unexpectedly induces IL-1beta production in conventional dendritic cells (cDCs) via a STAT3-dependent but NF-kappaB-independent pathway. IL-21 does not induce Il1b expression in CD4(+) T cells, with differential histone marks present in these cells versus cDCs. IL-21-induced IL-1beta processing in cDCs does not require caspase-1 or caspase-8 but depends on IL-21-mediated death and activation of serine protease(s). Moreover, STAT3-dependent IL-1beta expression in cDCs at least partially explains the IL-21-mediated pathologic response occurring during infection with pneumonia virus of mice. These results demonstrate lineage restricted IL-21-induced IL-1beta via a non-canonical pathway and provide evidence for its importance in vivo. PMID- 26269260 TI - Auto-immunity, allergy and Inflammation. PMID- 26269259 TI - Imaging Suprachoroidal Layer in Exudative Age-Related Macular Degeneration. AB - PURPOSE: To evaluate the prevalence of a visible suprachoroidal layer (SCL) on optical coherence tomography (OCT) in exudative age-related macular degeneration (AMD). MATERIALS AND METHODS: This retrospective study included 252 eyes of 252 patients with treatment-naive typical exudative AMD (n = 80), polypoidal choroidal vasculopathy (PCV) (n = 138) and retinal angiomatous proliferation (RAP) (n = 34). The presence of SCL was identified based on enhanced-depth imaging OCT images, and the prevalence was compared among the three disease groups. In addition, subfoveal choroidal thickness was compared between patients with and without SCL. RESULTS: The SCL was noted in 56 eyes (22.2%). The prevalence was 22.5% in typical exudative AMD (18 of 80 eyes), 18.8% in PCV (26 of 138 eyes) and 35.3% in RAP (12 of 34 eyes) (p = 0.118). Patients with SCL showed significantly thinner choroid (207.5 +/- 83.9 um versus 279.7 +/- 116.5 um, p < 0.001) and were relatively older (72.1 +/- 8.1 versus 70.1 +/- 8.7 years, p = 0.124) than those without SCL. CONCLUSION: The prevalence of visible SCL was 22.2% in patients with exudative AMD. Age-related changes, including choroidal thinning, may contribute to the development of a visible SCL. PMID- 26269262 TI - Cancer. PMID- 26269263 TI - Cell adhesion and repair. PMID- 26269264 TI - Clinical research. PMID- 26269265 TI - Epidermal structure and function. PMID- 26269266 TI - Genetic disorders and disease mechanisms. PMID- 26269267 TI - Hair, cutaneous homeostasis and stem cells. PMID- 26269268 TI - Immunology. PMID- 26269269 TI - Photobiology and pigmentation. PMID- 26269278 TI - New regression model for predicting hand-arm vibration (HAV) of Malaysian Army (MA) three-tonne truck steering wheels. AB - OBJECTIVE: The objective of this study was to present a new method for determination of hand-arm vibration (HAV) in Malaysian Army (MA) three-tonne truck steering wheels based on changes in vehicle speed using regression model and the statistical analysis method known as Integrated Kurtosis-Based Algorithm for Z-Notch Filter Technique Vibro (I-kaz Vibro). METHODOLOGY: The test was conducted for two different road conditions, tarmac and dirt roads. HAV exposure was measured using a Bruel & Kjaer Type 3649 vibration analyzer, which is capable of recording HAV exposures from steering wheels. The data was analyzed using I kaz Vibro to determine the HAV values in relation to varying speeds of a truck and to determine the degree of data scattering for HAV data signals. RESULTS: Based on the results obtained, HAV experienced by drivers can be determined using the daily vibration exposure A(8), I-kaz Vibro coefficient (Z(v)(infinity)), and the I-kaz Vibro display. The I-kaz Vibro displays also showed greater scatterings, indicating that the values of Z(v)(infinity) and A(8) were increasing. Prediction of HAV exposure was done using the developed regression model and graphical representations of Z(v)(infinity). The results of the regression model showed that Z(v)(infinity) increased when the vehicle speed and HAV exposure increased. DISCUSSION: For model validation, predicted and measured noise exposures were compared, and high coefficient of correlation (R(2)) values were obtained, indicating that good agreement was obtained between them. By using the developed regression model, we can easily predict HAV exposure from steering wheels for HAV exposure monitoring. PMID- 26269279 TI - Reproductive disorders in hairdressers and cosmetologists: a meta-analytical approach. AB - OBJECTIVES: The aim of this study was to perform a systematic review and to use a meta-analytical approach to assess quantitatively the risk of adverse pregnancy outcomes in hairdressers and cosmetologists. METHODS: A systematic literature search up to 1 February 2012 was carried out using major bibliographic databases, grey literature, contacts with research teams working on the subject, review papers and reference lists of selected articles. Observational studies reporting measures of effects in relation with body care (hairdressers, cosmetologists, etc.) and reproductive disorders were included. Study quality was assessed by three reviewers. The estimated risk ratios (RR) from all studies reporting on identical outcomes were combined using an average of logarithm transformation of estimated RR weighted by their inverted variance. Statistical heterogeneity across studies was assessed using Cochran's Q test. To explore the sources of heterogeneity, several sensitivity analyses and subgroup analyses were conducted based on study quality, country, study period, alcohol consumption, smoking habit, jobs and control populations. RESULTS: Nineteen studies were selected and reviewed in-depth. The combined risk ratios (RRcs) of five reproductive outcomes were calculated and found to be significantly increased for four outcomes: time to pregnancy, which had an RRc of 1.11 (95% CI: 1.03-1.19); premature birth, which had an RRc of 1.05 (95% CI: 0.99-1.11); small for gestational age, which had an RRc of 1.24 (95 CI%: 1.10-1.41); low birth weight, which had an RRc of 1.21 (95% CI: 1.06-1.39); and embryonic and fetal losses, which had an RRc of 1.19 (95% CI: 1.03-1.38). CONCLUSIONS: This work confirms a weak increase in risk of some reproductive disorders in female hairdressers/cosmetologists. However, the evidence level is rather weak, and a causal association between job and reproductive outcomes cannot be asserted. PMID- 26269280 TI - Review of health issues of workers engaged in operations related to the accident at the Fukushima Daiichi Nuclear Power Plant. AB - OBJECTIVES: The aim of this review was to summarize the lessons learned from the experience in protecting the health of workers engaged in operations following the accident at the Fukushima Daiichi Nuclear Power Plant (NPP). METHODS: We reviewed all types of scientific papers examining workers' health found in Medline and Web of Sciences as well as some official reports published by the Ministry of Health, Labour and Welfare of Japan and other governmental institutes. RESULTS: The papers and reports were classified into those investigating workers at the Fukushima Daiichi and Daini NPPs, workers engaged in decontamination operations in designated areas, and other workers. Regarding workers at the NPPs, many efforts were made to establish an emergency-care and occupational health system. Risk management efforts were undertaken for radiation exposure, heat stress, psychological stress, outbreak of infectious diseases, and fitness for work. Only a few reports dealt with decontamination workers and others; however, the health management of these workers was clearly weaker than that for workers at the NPPs. CONCLUSIONS: Many lessons can be learned from what occurred. That knowledge can be applied to ongoing decommissioning work and to future disasters. In addition, it is necessary to study the long-term health effects of radiation exposure and to accumulate data about the health of workers engaged in decontamination work and other areas. PMID- 26269281 TI - Multi-modal assessment of on-road demand of voice and manual phone calling and voice navigation entry across two embedded vehicle systems. AB - One purpose of integrating voice interfaces into embedded vehicle systems is to reduce drivers' visual and manual distractions with 'infotainment' technologies. However, there is scant research on actual benefits in production vehicles or how different interface designs affect attentional demands. Driving performance, visual engagement, and indices of workload (heart rate, skin conductance, subjective ratings) were assessed in 80 drivers randomly assigned to drive a 2013 Chevrolet Equinox or Volvo XC60. The Chevrolet MyLink system allowed completing tasks with one voice command, while the Volvo Sensus required multiple commands to navigate the menu structure. When calling a phone contact, both voice systems reduced visual demand relative to the visual-manual interfaces, with reductions for drivers in the Equinox being greater. The Equinox 'one-shot' voice command showed advantages during contact calling but had significantly higher error rates than Sensus during destination address entry. For both secondary tasks, neither voice interface entirely eliminated visual demand. Practitioner Summary: The findings reinforce the observation that most, if not all, automotive auditory vocal interfaces are multi-modal interfaces in which the full range of potential demands (auditory, vocal, visual, manipulative, cognitive, tactile, etc.) need to be considered in developing optimal implementations and evaluating drivers' interaction with the systems. Social Media: In-vehicle voice-interfaces can reduce visual demand but do not eliminate it and all types of demand need to be taken into account in a comprehensive evaluation. PMID- 26269283 TI - A 61-year-old man with hyperpigmentation. Ochronosis. PMID- 26269284 TI - Correction. Application of a mortality risk score in a general population of patients with an implantable cardioverter defibrillator (ICD). PMID- 26269285 TI - High resolution skin-like sensor capable of sensing and visualizing various sensations and three dimensional shape. AB - Human skin contains multiple receptors, and is able to sense various stimuli such as temperature, pressure, force, corrosion etc, and to feel pains and the shape of objects. The development of skin-like sensors capable of sensing these stimuli is of great importance for various applications such as robots, touch detection, temperature monitoring, strain gauges etc. Great efforts have been made to develop high performance skin-like sensors, but they are far from perfect and much inferior to human skin as most of them can only sense one stimulus with focus on pressure (strain) or temperature, and are unable to visualize sensations and shape of objects. Here we report a skin-like sensor which imitates real skin with multiple receptors, and a new concept of pain sensation. The sensor with very high resolution not only has multiple sensations for touch, pressure, temperature, but also is able to sense various pains and reproduce the three dimensional shape of an object in contact. PMID- 26269286 TI - Polyaspartic acid enhances dentine remineralization bonded with a zinc-doped Portland-based resin cement. AB - AIM: To ascertain whether biomimetic phosphoprotein analogues (polyaspartic acid (PAS) and sodium trimetaphosphate (TMP)) improve bonding efficacy and dentine remineralization ability of a novel zinc-doped Portland-based resinous sealing cement. METHODOLOGY: Bonding procedures were performed on phosphoric acid-etched dentine, and several groups were established regarding biomimetic analogue application: (1) no application, (2) PAS-treated dentine and (3) dentine treated with a mixture of PAS and TMP. Raman spectroscopy and microtensile bond strength (MTBS) with fracture analysis by scanning electron microscopy were carried out. MTBS values were compared by anova, Student-Newman-Keuls and Student's t-tests (P < 0.05 and P < 0.01, respectively). RESULTS: Twenty-four hour MTBS values were not affected by the different bonding procedures. After 6 months, MTBS decreased in those groups in which the phosphoproteins analogues were not applied (P < 0.05). When PAS was applied, MTBS was maintained after 6 months (P > 0.05). The novel material bonded without primer application induced bioactive crystal (calcium carbonate and Ettringite) precipitation onto the etched dentine and augmented the degree of crystallinity at the hybrid layer. Mineral-to-matrix ratio was increased at the hybrid layer of the PAS-treated specimens; this primer was also able to catalyse dentine remineralization, without an increase in crystallinity. CONCLUSIONS: PAS application onto demineralized dentine produced an inhibition or delay of mineral phase crystallization, enhancing the remineralization potential of the Portland microfillers at the resin-dentine bonded interface. PMID- 26269288 TI - Changes to the dynamic nature of hemagglutinin and the emergence of the 2009 pandemic H1N1 influenza virus. AB - The virologic factors that limit the transmission of swine influenza viruses between humans are unresolved. While it has been shown that acquisition of the neuraminidase (NA) and matrix (M) gene segments from a Eurasian-lineage swine virus was required for airborne transmission of the 2009 pandemic H1N1 virus (H1N1pdm09), we show here that an arginine to lysine change in the hemagglutinin (HA) was also necessary. This change at position 149 was distal to the receptor binding site but affected virus-receptor affinity and HA dynamics, allowing the virus to replicate more efficiently in nasal turbinate epithelium and subsequently transmit between ferrets. Receptor affinity should be considered as a factor limiting swine virus spread in humans. PMID- 26269289 TI - [Current aspects of therapy conversion for multiple sclerosis]. AB - In recent years the approval of new substances has led to a substantial increase in the number of course-modifying immunotherapies available for multiple sclerosis. Therapy conversion therefore represents an increasing challenge. The treatment options sometimes show complex adverse effect profiles and necessitate a long-term and comprehensive monitoring. This article presents an overview of therapy conversion of immunotherapies for multiple sclerosis in accordance with the recommendations of the Disease-Related Competence Network for Multiple Sclerosis and the German Multiple Sclerosis Society as well as the guidelines on diagnostics and therapy for multiple sclerosis of the German Society of Neurology and the latest research results. At the present point in time it should be noted that no studies have been carried out for most of the approaches for therapy conversion given here; however, the recommendations are based on theoretical considerations and therefore correspond to recommendations at the level of expert consensus, which is currently essential for the clinical daily routine. PMID- 26269291 TI - Parents Taking Action: A Psycho-Educational Intervention for Latino Parents of Children With Autism Spectrum Disorder. AB - The increased prevalence of autism spectrum disorder (ASD) among Latino children, later diagnosis, limited access to bicultural specialist support, and worsened health outcomes when compared to non-Latinos points to the need for a culturally relevant parent education intervention. This pilot study examined the feasibility, acceptability, and preliminary outcomes of a culturally derived intervention, Parents Taking Action, for 19 Spanish-speaking mothers of children with ASD. This study introduces the Promotora de Salud Model of intervention delivery to the autism field. A mixed-methods design including one group pre- and posttest design and focus groups was used to evaluate the outcomes of PTA. We found that the intervention was both feasible to implement and acceptable to participants. We also found significant increases in empowerment oriented outcomes for parents between pre- and posttest suggesting that the intervention is promising. Suggestions for future research and practice are offered. PMID- 26269290 TI - The circular relationship between matrix metalloproteinase-9 and inflammation following myocardial infarction. AB - Matrix metalloproteinase-9 (MMP-9) regulates remodeling of the left ventricle after myocardial infarction (MI) and is tightly linked to the inflammatory response. The inflammatory response serves to recruit leukocytes as part of the wound healing reaction to the MI injury, and infiltrated leukocytes produce cytokines and chemokines that stimulate MMP-9 production and release. In turn, MMP-9 proteolyzes cytokines and chemokines. Although in most cases, MMP-9 cleavage of the cytokine or chemokine substrate serves to increase activity, there are cases where cleavage results in reduced activity. Global MMP-9 deletion in mouse MI models has proven beneficial, suggesting inhibition of some aspects of MMP-9 activity may be valuable for clinical use. At the same time, overexpression of MMP-9 in macrophages has also proven beneficial, indicating that we still do not fully understand the complexity of MMP-9 mechanisms of action. In this review, we summarize the cycle of MMP-9 effects on cytokine production and cleavage to regulate leukocyte functions. Although we use MI as the example process, similar events occur in other inflammatory and wound healing conditions. PMID- 26269292 TI - Assessment of Substantial Liver Fibrosis by Real-time Shear Wave Elastography in Methotrexate-Treated Patients With Rheumatoid Arthritis. AB - OBJECTIVES: A concern about methotrexate (MTX)-related liver fibrosis in patients with rheumatoid arthritis (RA) is still unresolved. This study investigated the correlation between liver stiffness and the cumulative MTX dose and the risk factors associated with substantial liver fibrosis assessed by real-time shear wave elastography (SWE), a recently introduced technique to evaluate liver stiffness in patients with RA. METHODS: Data from 185 patients with RA were prospectively collected. Patients were divided into 3 groups according to cumulative MTX dose (group 1, total dose <1500 mg; group 2, 1500-4000 mg, and group 3, >4000 mg) and compared with healthy control participants. A Pearson correlation analysis was performed to evaluate correlations between liver stiffness and other clinical and laboratory variables. Substantial liver fibrosis was defined as liver stiffness of greater than 8.6 kPa by SWE. Associated factors were tested in a multivariate logistic analysis. RESULTS: The mean liver stiffness value in healthy controls was significantly lower than in patients with RA treated with MTX (P< .006), but there was no significant difference among the MTX groups. Liver stiffness and the cumulative MTX dose was not correlated. Substantial liver fibrosis was detected only in 9 patients (4.9%). Multivariate analysis adjusted by age and sex revealed that only a high body mass index (odds ratio, 1.79; 95% confidence interval, 1.34-2.39; P < .001) was associated with liver stiffness of greater than 8.6 kPa. CONCLUSIONS: Substantial liver fibrosis on SWE was observed in about 5% of MTX-treated patients with RA and was associated with only a high body mass index but not with the cumulative MTX dose, suggesting that other comorbidities might have a more important role in liver fibrosis. PMID- 26269293 TI - Cardiac Limited Ultrasound Examination Techniques to Augment the Bedside Cardiac Physical Examination. AB - The current practice of physical diagnosis is dependent on physician skills and biases, inductive reasoning, and time efficiency. Although the clinical utility of echocardiography is well known, few data exist on how to integrate 2 dimensional screening "quick-look" ultrasound applications into a novel, modernized cardiac physical examination. We discuss the evidence basis behind ultrasound "signs" pertinent to the cardiovascular system and elemental in synthesis of bedside diagnoses and propose the application of a brief cardiac limited ultrasound examination based on these signs. An ultrasound-augmented cardiac physical examination can be taught in traditional medical education and has the potential to improve bedside diagnosis and patient care. PMID- 26269294 TI - Local Recurrent Phyllodes Tumors of the Breast: Clinical and Sonographic Features. AB - OBJECTIVES: The purpose of this study was to investigate the clinical, pathologic, and sonographic features of local recurrent phyllodes tumors of the breast and provide evidence for diagnosing tumor recurrence. METHODS: A total of 127 patients with phyllodes tumors who underwent surgery from 1993 to 2012 were followed. The clinical, pathologic, and sonographic features of local recurrent tumors were analyzed. RESULTS: Of the 127 patients, pathologic diagnoses were benign, borderline, and malignant in 75 (59.1%), 41 (32.3%), and 11 (8.7%) patients, respectively. The patients were followed for a mean duration +/- SD of 50.9 +/- 42.1 months (range, 2-225 months). Twenty-one patients had local recurrence, for a recurrence rate of 16.5%. The benign, borderline, and malignant recurrence rates were 14.7%, 17.1%, and 27.3%. The local recurrence in the 21 patients occurred after a mean interval of 19.4 +/- 13.4 months. The mean times to local recurrence were 20.2 +/- 12.1, 16.9 +/- 10.8, and 20.3 +/- 19.0 months for benign, borderline, and malignant tumors. The histologic characteristics of the recurrent tumors were similar to those of the initial tumors in 14 patients (66.7%), whereas the characteristics changed in 7 (33.3%). The sonographic features of the recurrent tumors were as follows: 69.4% were lobulated; 88.9% appeared as well-defined lesions; 41.7% had posterior acoustic enhancement; 11.1% had intramural cystic areas; and 83.4% had moderate or marked blood flow. CONCLUSIONS: The recurrence rate for phyllodes tumors is high. One to 2 years after surgery is the key time for follow-up. The sonographic features contribute to recurrence diagnosis. PMID- 26269295 TI - Optic Nerve Sheath Diameter Increase on Ascent to High Altitude: Correlation With Acute Mountain Sickness. AB - OBJECTIVES: Elevated optic nerve sheath diameter on sonography is known to correlate with increased intracranial pressure and is observed in acute mountain sickness. This study aimed to determine whether optic nerve sheath diameter changes on ascent to high altitude are associated with acute mountain sickness incidence. METHODS: Eighty-six healthy adults enrolled at 1240 m (4100 ft), drove to 3545 m (11,700 ft) and then hiked to and slept at 3810 m (12,500 ft). Lake Louise Questionnaire scores and optic nerve sheath diameter measurements were taken before, the evening of, and the morning after ascent. RESULTS: The incidence of acute mountain sickness was 55.8%, with a mean Lake Louise Questionnaire score +/- SD of 3.81 +/- 2.5. The mean maximum optic nerve sheath diameter increased on ascent from 5.58 +/- 0.79 to 6.13 +/- 0.73 mm, a difference of 0.91 +/- 0.55 mm (P = .09). Optic nerve sheath diameter increased at high altitude regardless of acute mountain sickness diagnosis; however, compared to baseline values, we observed a significant increase in diameter only in those with a diagnosis of acute mountain sickness (0.57 +/- 0.77 versus 0.21 +/- 0.76 mm; P = .04). This change from baseline, or Delta optic nerve sheath diameter, was associated with twice the odds of developing acute mountain sickness (95% confidence interval, 1.08-3.93). CONCLUSIONS: The mean optic nerve sheath diameter increased on ascent to high altitude compared to baseline values, but not to a statistically significant degree. The magnitude of the observed Delta optic nerve sheath diameter was positively associated with acute mountain sickness diagnosis. No such significant association was found between acute mountain sickness and diameter elevation above standard cutoff values, limiting the utility of sonography as a diagnostic tool. PMID- 26269296 TI - Intrathyroidal Ectopic Thymus in Children: Retrospective Analysis of Grayscale and Doppler Sonographic Features. AB - OBJECTIVES: The purpose of this study was to define grayscale and color Doppler sonographic features of an ectopic intrathyroidal thymus and to differentiate it from other thyroid nodule etiologies. METHODS: We retrospectively reviewed imaging findings from 30 children who had a diagnosis of an ectopic intrathyroidal thymus from November 2005 to January 2013. Nodular thyroid lesions that were enclosed by the thyroid parenchyma and showed a typical echo pattern consistent with the thymus were accepted as the enclosed form of an intrathyroidal ectopic thymus. Eleven of these 30 children had an intrathyroidal ectopic thymus enclosed by the thyroid parenchyma, and they were enrolled in the study. The recorded sonograms were reviewed according to side, location, size, shape, echo pattern, internal content, and vascularization. RESULTS: The enclosed forms of ectopic intrathyroidal thymuses were unilateral in all children and located in the mid portion (n = 10) or lower portion (n = 1). All lesions were well demarcated, and the most common shape was fusiform (n = 8). Nine lesions showed a typical hypoechoic echo pattern with internal linear and punctate echoes resembling a mediastinal thymus. On color Doppler imaging, 6 lesions showed hypovascularity compared to the thyroid parenchyma, and 5 lesions showed internal vascularity. CONCLUSIONS: Unique sonographic features of the enclosed form of an ectopic intrathyroidal thymus, including a hypoechoic echo pattern with multiple linear and punctate echoes, a fusiform shape, a well-demarcated contour, and a mid- or low-lying location with hypovascularity or internal vascularity, can help radiologists differentiate it from other thyroid nodule etiologies. PMID- 26269297 TI - Extension of the Thoracic Spine Sign: A New Sonographic Marker of Pleural Effusion. AB - OBJECTIVES: Dyspnea is a common emergency department (ED) condition, which may be caused by pleural effusion and other thoracic diseases. We present data on a new sonographic marker, the extension of the thoracic spine sign, for diagnosis of pleural effusion. METHODS: In this prospective study, we enrolled a convenience sample of undifferentiated patients who underwent computed tomography (CT) of the abdomen or chest, which was performed as part of their emergency department evaluations. Patients underwent chest sonography to assess the utility of the extension of the thoracic spine sign for diagnosing pleural effusion. The point of-care sonographic examinations were performed and interpreted by emergency physicians who were blinded to information in the medical records. Sonographic results were compared to radiologists' interpretations of the CT results, which were considered the criterion standard. RESULTS: Forty-one patients were enrolled, accounting for 82 hemithoraces. Seven hemithoraces were excluded from the analysis due to various limitations, leaving 75 hemithoraces for the final analysis. The median time for completion of the sonographic examination was 3 minutes. The sensitivity and specificity for extension of the thoracic spine were 73.7% (95% confidence interval [CI], 48.6%-89.9%) and 92.9% (95%CI, 81.9%-97.7%), respectively. Overall, there were 5 hemithoraces with false-negative results when using the extension sign. Of those 5 cases, 4 were found to have trace pleural effusions on CT. When trace pleural effusions were excluded in a subgroup analysis, the sensitivity and specificity of extension of the thoracic spine were 92.9% (95% CI, 64.2%-99.6%) and 92.9% (95% CI, 81.9%-97.7%). CONCLUSIONS: We found the extension of the thoracic spine sign to be an excellent diagnostic tool for clinically relevant pleural effusion. PMID- 26269298 TI - Fetal Diagnosis of d-Transposition of the Great Arteries Associated With a Double Aortic Arch. PMID- 26269299 TI - Diagnostic Efficacy and Safety of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Intrathoracic Tuberculosis: A Meta-analysis. AB - OBJECTIVES: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive technique. A meta-analysis was performed to assess the efficacy and safety of EBUS-TBNA in intrathoracic tuberculosis (TB). METHODS: We searched PubMed, the Cochrane Library, and the Web of Science for suitable studies. The pooled sensitivity, specificity, likelihood ratios (LRs), and diagnostic odds ratio were calculated. A summary receiver operating characteristic (ROC) curve was constructed to calculate the area under the summary ROC curve and Qpoint value (Q*). RESULTS: A total of 8 studies with 809 patients were included. The pooled sensitivity and specificity of EBUS-TBNA for diagnosis of intrathoracic TB were 0.80 (95% confidence interval [CI] 0.74-0.85) and 1.00 (95% CI, 0.99-1.00), respectively. The positive LR was 38.25 (95% CI, 13.59-107.65); the negative LR was 0.24 (95% CI, 0.17-0.33); and the diagnostic odds ratio was 186.35 (95% CI, 63.57-546.28). The area under the summary ROC curve was 0.935, and the Q*was 0.871. The pooled sensitivity of EBUS-TBNA for diagnosis of intrathoracic tuberculous lymphadenopathy was 0.87 (95% CI, 0.80 0.95). Only 1 serious complication was reported. CONCLUSIONS: Endobronchial US guided TBNA is an effective and safe diagnostic tool for intrathoracic TB, especially intrathoracic tuberculous lymphadenopathy. PMID- 26269300 TI - Risk Evaluation of Immediate Surgical Failure During Thigh Hemodialysis Graft Placement by Sonographic Screening. AB - OBJECTIVES: The purpose of this study was to determine whether preoperative sonographic evaluation of vascular diameters and calcification identifies patients at risk for immediate technical failure of thigh hemodialysis grafts. METHODS: A retrospective analysis of 143 chronic hemodialysis patients who underwent thigh graft placement was performed. All patients underwent preoperative sonography to assess arterial and venous waveforms and vascular diameters. The degree of arterial calcification was assessed retrospectively. Patient characteristics and graft outcomes were examined. Statistical analyses were performed, with P< .05 considered clinically significant. RESULTS: Sonography identified no or mild arterial calcification in 113 of 143 patients (79%) and moderate to severe calcification in 30 of 143 patients (21%). Primary surgical technical failure occurred in 23% of patients (7 of 30) with moderate to severe calcification, compared to 3.5% (4 of 113) of those with no or mild calcification (hazard ratio, 6.59; 95% confidence interval, 2.06-21.05; P = .002). Cumulative graft survival (time to permanent failure) was shorter in patients with moderate to severe arterial calcification (3-year graft survival, 37% versus 56%; hazard ratio, 2.32; 95% confidence interval, 1.48-6.69; P= .003) but was not significantly associated with venous (P= .82) or arterial (P = .43) diameters. CONCLUSIONS: Preoperative sonographic assessment of thigh vessel diameters and calcification can identify patients who may be at risk for immediate technical graft failure and decreased cumulative graft survival. The use of sonography as a screening examination may improve preoperative assessment and surgical planning of hemodialysis thigh grafts. PMID- 26269302 TI - [Anesthesia method of bronchoscopy and clarifying the concept of painless bronchoscopy]. PMID- 26269301 TI - Examination of Subcutaneous Tissue Thickness in the Thigh Site for Intramuscular Injection in Obese Individuals. AB - OBJECTIVES: The aim of the study was to investigate the thickness of subcutaneous (SC) tissue in the dorsogluteal and thigh sites in obese adults and its suitability for intramuscular injection using a standard-length needle. METHODS: The sample for this prospective study consisted of 54 obese adults who presented to the ultrasound unit of the radiology clinic of a university hospital in the province of Izmir, Turkey, between June 2012 and August 2013. The study received Institutional Review Board approval, and informed written consent was obtained from all participants. The thickness of the SC tissue in the dorsogluteal and thigh sites was measured by sonography. The sonographic measurements were performed by a radiology specialist. RESULTS: The mean thicknesses of the SC tissue were 61.70 +/- 15.73 mm in the dorsogluteal site, 27.05 +/- 8.52 mm in the rectus femoris site, and 23.23 +/- 8.44 mm in vastus lateralis site. The SC tissue was thicker in the dorsogluteal than the thigh site (P < .001). CONCLUSIONS: A standard needle used in intramuscular injections to the thigh site would be effective in reaching the muscle in the rectus femoris and vastus lateralis sites in all men and in 77.8% of women, although it is not usually adequate for gluteal injection. PMID- 26269303 TI - [The application of autofluorescence bronchoscopy in guiding surgical resection range for lung cancer]. AB - OBJECTIVE: To explore the value of autofluorescence bronchoscopy in guiding surgical resection range for central lung cancer. METHODS: A total of 213 patients with lung cancer were evaluated by both light bronchoscopy (WLB) and autofluorescence bronchoscopy (AFB) by BF-F260 (Olympus, Japan) before surgery from Mar. 2012 to Feb. 2013. The number of positive cases under each mode, clinical stage, surgical resection range and surgical options were evaluated to explore diagnostic value of WLB and AFB. RESULTS: Of the 213 cases, surgical margins were negative in 198 cases, while the remaining 15 cases were found to be inoperable. A total of 1 146 biopsies from different sites including neoplasm and bronchial mucosa were evaluated for tumor involvement by pathology. On average, biopsy was performed 5.0 +/- 1.2 times for each patient. The sensitivity of the WLB group and the AFB group was 65. 2% (214/662) and 81.2% (237/484), and the specificity was 74.8% (214/662) and 54.7% (237/484), respectively, the difference being statistically significant (chi2 = 19.747, P < 0.05). Bronchial mucosal invasion was found by fluorescence bronchoscopy and the surgical procedures were changed in 27 case: from lobectomy to bilobectomy and pneumonectomy in 10, from lobectomy to inoperable in 2, from lobectomy to interlobar ridge plasty( sleeve resection) in 8, from pneumonectomy to inoperable in 3, and from pneumonectomy to carina plasty in 4 cases. In all the 213 patients, 214 pathological positive sites were found in the WLB group and 237 in the AFB group. The difference being statistically significant (chi2 = 32.439, P < 0.05). CONCLUSION: Autofluorescence bronchoscopy showed a high sensitivity for lung cancer, and was helpful to guide surgical resection range and reduce postoperative recurrence rate. PMID- 26269304 TI - [Pleural epithelioid hemangioendothelioma: a case report and review of the literature]. AB - OBJECTIVE: To explore the etiology, clinical manifestation, diagnosis, differential diagnosis, management and prognosis of pleural epithelioid hemangioendothelioma. METHODS: The clinical data of a patient with pleural epithelioid hemangioend othelioma admitted to Peking Union Medical College Hospital were retrospectively analyzed and the related literature was reviewed. We searched databases PubMed, Embase, Ovid, Cochrane, Wanfang and Chinese National Knowledge infrastructure (CNKI) using the keyword "pleural epithelioid hemangioendothelioma" by December 2013. RESULTS: The patient was a 40-year-old male presented with chest pain, and his chest CT scan revealed thickening of the left pleura and left pleural effusion. Biopsy of the pleura showed epithelioid tumor cells, and immunohistochemistry was positive for CD31, CD34 and vimentin. From January 1975 to December 2013, 18 related articles were retrieved and 29 cases of pleural epithelioid hemangioendothelioma were reported. Among all 30 cases, there were 20 males and 10 females, ranging from 31 to 82 years old, and the average age was 50. 3 years old. The etiology of the disease remained unknown. Chest pain, cough, and dyspnea were the common symptoms. Computed tomography usually revealed pleural effusion and pleural thickening or mass. Histological examinations revealed mainly epithelioid cells. Immunohistochemical stains were positive for vascular endothelial markers. The mean survival time was 8.2 months. CONCLUSIONS: Pleural epithelioid hemangioendothelioma is rare and the etiology is unknown. Clinical and imaging manifestations are not specific, and diagnosis is relied on histological findings. It should be differentiated from adenocarcinoma, hemangiosarcoma, mesothelioma and pulmonary epithelioid hemangioendothelioma. There is no effective treatment and its prognosis is poorer than its pulmonary counterpart. PMID- 26269305 TI - [Effects of ozone oxidative stress on the airway hyperresponsiveness and mucus production in mice with acute allergic airway inflammation]. AB - OBJECTIVE: To explore the impact of ozone on the airway hyperresponsinveness (AHR), airway inflammation and mucus production in an allergic asthma mouse model. METHODS: Twenty-eight female BALB/c mice were randomly divided into 4 equal groups: healthy control, ozone control, asthma model, and ozone intervention. For asthma model establishing, the mice were sensitized and challenged with ovalbumin, while the controls received saline. For ozone exposure, the mice were exposed to 2.0 ppm ozone for 3 hrs, while the control treatment group exposed to filtered air for 3 hrs. Some measurements were performed 24 hrs after the exposure, including AHR, pulmonary inflammation, mucus secretion, epithelial barrier function, and the level of oxidant stress. RESULTS: Compared with the asthma model group, mice in the ozone intervention group exhibited lower LogPC100Penh (0.22 +/- 0.09 vs 0.50 +/- 0.19, t = 3.06, P = 0.006), higher bronchoalveolar lavage (BAL) neutrophil numbers [(0.80 +/- 0.21) x 10(3)/L vs (0.15 +/- 0.06) x 10(3)/L, t = 3.63, P = 0.019] and BAL concentration of lower molecular weight hyaluronan (LMW-HA) [(111 +/- 17) ug/L vs (35 +/- 18) ug/L, t = 5.12 P = 0.000], TNF-alpha[(155 +/- 30) ug/L vs (86 +/-19) ug/L, t = 2.15, P = 0.044] and IL-13 [(65 +/- 11) ug/L vs (33 +/- 20) ug/L, t = 2.95, P = 0.008]. Mice in the ozone intervention group showed higher lung pathological inflammation score (2. 80 0.10 vs 1.92 +/- 0.23, t =3.91, P = 0.000) and upregulated expressions of TNF-alpha mRNA (7.0 +/- 1.5 vs 3.57 +/- 1.20, t = 2.65, P = 0.014), CXCL-1 mRNA (7.0 +/- 1.1 vs 2.5 +/- 1.0, t = 4.12, P = 0.000) and IL-17 mRNA (28.8 +/- 5.2 vs 16.4 +/- 4.4, t = 6.33, P = 0.000). Ozone exposure on the asthmatic mice also caused higher percentage of PAS positive staining epithelial cells [(76.2 +/- 8.7) % vs (55.8 +/- 14.4) %, t = 8.14, P = 0.000] and higher epithelial surface mucus volume [(721 +/- 584) nl/mm2 vs (272 +/- 185) nl/mm2, t = 5.78, P = 0.000] as well as the MUC5ac mRNA expression (15.4 +/- 4.6 vs 7.0 +/- 1.9, t = 4.37, P = 0.000). Besides, ozone exposure in the asthma model decreased epithelial cell density (82 +/- 22 vs 116 +/- 15, t = 10.1, P = 0.000), while increased the BAL concentration of albumin [(45 +/- 6) g/L vs (33 +/- 4) g/L, t = 3.89, P = 0.001] . CONCLUSIONS: Ozone exaggerates AHR and pulmonary inflammation, and causes damages in epithelial cells and promotes the production of epithelial mucus. PMID- 26269307 TI - [Multiple growth-factor-releasing system stimulates proliferation of human embryonic lung fibroblasts in vitro]. AB - OBJECTIVE: To investigate the most effective method to promote human embryonic lung fibroblast proliferation, we established several novel local fibrin-gel delivery systems, which could continuously release multiple growth factors in vitro. METHODS: Multiple growth factors, including platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor (TGF) and epidermal growth factor (EGF) were added to fibrinogen solutions. These multiple growth-factor-containing fibrinogen solutions were converted to fibrin gel using thrombin to establish a delivery system. The kinetics and dissolution curves of the different fibrin-gel delivery systems were determined by daily measurement of the dissolved collagen volume. Human embryonic lung fibroblasts were randomly divided into 2 groups: the growth-factors (group A) and the non growth-factors groups (group B). Based on the fibrin-gel shape, groups A and B were both randomly divided into 4 sub-groups; the fully-covered fibrin-gel, island fibrin-gel, scattered punctiform fibrin-gel and medium without fibrin-gel control groups. Cell proliferation was determined by cell counting and cell viability using the methyl thiazolyl tetrazolium (MTT) assay. Cell proliferation rate was measured by MTT. RESULTS: (1) The peak of growth factors releasing from gel of island group was 8.2 +/- 0.8 days, while that of scattered punctiform group was 8.0 +/- 1.0 days, and that of the fully-covered fibrin-gel group was 9.8 +/- 0.4 days. The trend of growth factor releasing was significantly different among groups (F = 31.054, P < 0.05). There was no statistical difference in the release kinetics between the island group and the scattered punctiform group ( t = 1. 000, P > 0. 05). The peak of growth factors releasing from gel of the fully-covered fibrin-gel group was later than that of the island groups and the scattered punctiform fibrin-gel group (t = 6.820, P < 0.01). (2) The cell proliferation rate of island gel containing growth factors subgroup (107.6 +/- 1.1) % grew more rapidly than island gel without growth factors subgroup (73.2 +/- 2.2) % (F = 375.29, P < 0.01). The cell proliferation rate of the scattered punctiform gel containing growth factors subgroup (141.2 +/- 1.8) % grew more rapidly than the scattered punctiform gel without growth factors subgroup (106.0 +/- 2.8)% (F = 2274.48, P < 0.01). (3) The trend of growth factor releasing of the scattered punctiform group was significantly faster than that of the island group (F = 12.392, P < 0.01). CONCLUSION: (1) Multiple growth factors, including PDGF, TGF, VEGF and EGF, stimulate human embryonic lung fibroblast growth and proliferation. (2) The enhancement effect of the scattered punctiform fibrin-gel multiple growth-factor-releasing system on cell growth and proliferation was greater compared with the island fibrin-gel multiple growth factor-releasing system. PMID- 26269306 TI - [Effects of chitin micro-particles on airway inflammation in a mouse neutrophilic asthmatic model]. AB - OBJECTIVE: To investigate the impact of chitin micro-particles ( CMPs) on the airway inflammation and the cytokine levels of IL-10 and IL-17 in mice with neutrophilic asthma (NA). METHODS: Thirty 4- to 6-week-old BALB/c mice were divided into 5 groups based on random number table: healthy control group, CMP control group (CMP intervention, PBS sensitization and PBS challenge), NA group (PBS intervention, OVA + LPS sensitization and OVA challenge), CMP treatment group (CMP intervention, OVA + LPS sensitization and OVA challenge) , and DXM treatment group ( DXM intervention, OVA + LPS sensitization and OVA challenge). Each group included 6 mice. Twenty four hours (24 h) after the last challenge, airway resistance was measured, bronchoalveolar lavage fluid (BALF) and serum were collected, and lung tissue was taken for HE staining. Wright's staining was performed on BALF for white blood cell differential count. The ELISA method was used to determine the content of cytokine IL-17 in BALF and lung tissue homogenate and the content of cytokine IL-10 in serum. RESULTS: A large number of inflammatory cells infiltrated the surroundings of bronchus and blood vessel in the NA group. The airway inflammation in the CMP treatment group was significantly milder than that in the NA group and the DXM treatment group, but more severe than that in the healthy control group and the CMP control group. The number of BALF neutrophils in the CMP treatment group [(5.1 +/- 2.0) x 10(5)/ml] was significantly lower than that in the NA group [(9.2 +/- 2.0) x 10(5)/ml] and the DXM treatment group [(7.9 +/- 2.3) x 10(5)/ml], but higher than that in the healthy control group [(1.4 +/- 0.4 ) x 10(5)/ml] and the CMP control group [(1.5 +/- 0.7) x 10(5)/ml], the difference being statistically significant (F = 27.1, P < 0.05). The content of IL-10 in serum in the CMP treatment group increased significantly [(80 +/- 16) ng/L], and was higher than that in the NA group [(15 +/- 8) ng/L], the healthy control group [(29 +/- 10) ng/L], the CMP control group [(28 +/- 7) ng/L] and the DXM treatment group [(18 +/- 10) ng/L] (F = 37.1, P < 0.05). The content of IL-17 in BALF in the CMP treatment group [(86 +/- 10) ng/L] was significantly lower than that in the NA group [(111 +/- 11) ng/L] and the DXM treatment group [(101 +/- 9) ng/L], but higher than that in the healthy control group [(63 +/- 10) ng/L] and the CMP control group [(65 +/- 8) ng/L] (F = 32.2, P < 0.05). CONCLUSION: CMP may alleviate the airway inflammation of mice with neutrophilic asthma by reducing IL-17 in airways. PMID- 26269308 TI - [The role of nuclear factor-kappaB in endothelial cell inflammatory injury by intermittent hypoxia in rat with emphysema]. AB - OBJECTIVE: To investigate mechanism underlying the role of nuclear factor Kappa B (NF-kappaB) which induced inflammatory injury and functional lesions of aortic endothelial cells in rat with emphysema and intermittent hypoxia. METHODS: Sixty male Wistar rats were divided randomly into 4 experimental groups (n = 15 each group): control group, emphysema group, intermittent hypoxia (IH) group, emphysema with intermittent hypoxia group. The rats in control group had ad libitum access to food and water under normal circumstance. The rats in the emphysema group were exposed to cigarette smoke twice daily (30 min each time). As for IH group, the rats were exposed to intermittent hypoxia circumstance (8 h/day). Both cigarette smoke twice a day (30 min each time) and intermittent hypoxia circumstance (8 h/day) were imposed on the rats in emphysema with intermittent hypoxia group. All the rats were exposed for 8 weeks. Five rats were randomly selected from each group to measure the blood gas on the ninth week. We collected lung and endothelial tissues of thoracic aorta from the rest sacrificed rats, and observed the pathological changes of lung tissue through HE staining. The levels of ET-1, TNF-alpha and IL-8 in rat endothelial tissues of thoracic aorta were measured by ELISA testing. Nitrate reductase was used to measure the levels of NO, and RT-PCR to detect the levels of NF-kappaB mRNA, ICAM-1 mRNA, MMP 9 mRNA and eNOS mRNA. RESULTS: Lung pathology and blood gas results showed that the rat model of emphysema with intermittent hypoxia was established successfully. The levels of ET-1, TNF-alpha, IL-8 in emphysema with intermittent hypoxia group were (172.4 +/- 1.6) ng/L, (104.1 +/- 1.4) ng/L, (272.1 +/- 3.6) ng/L respectively, significantly higher than the control group, emphysema group and intermittent hypoxia group (all P < 0.05). The level of NO was (27.07 +/- 0.57) umol/L, which was significant reduced; the expression of NF-kappaB mRNA, ICAM-1 mRNA, MMP-9 mRNA in emphysema with intermittent hypoxia group was significantly upregulated compared with the control goup, emphysema group and intermittent hypoxia group (all P < 0.05). The levels of eNOS mRNA expression were significantly lower than other three groups. The expression of NF-kappaB mRNA was positively correlated with MMP-9 mRNA level (r = 0.572, P < 0.001) and the expression of NF-kappaB mRNA was negatively correlated with eNOS mRNA level (r = 0.534, P < 0.001); there was no statistical difference in levels of NF kappaB mRNA and eNOS mRNA expression between intermittent hypoxia and emphysema group (P > 0.05). CONCLUSION: Compared with only emphysema or intermittent hypoxia exposure, inflammatory injury of aortic endothelial cells of rats induced by emphysema with intermittent hypoxia was more serious, and may result in more serious cardiovascular complications. The activation of NF-kappaB pathway may be an important mechanism of its inflammatory response. PMID- 26269310 TI - [Advances in mechanical ventilation guided by respiratory mechanics in acute respiratory distress syndrome]. PMID- 26269309 TI - [Transforming growth factor-beta1 induces epithelial-mesenchymal transition in A549 cells by up-regulating expression of calpain]. AB - OBJECTIVE: To investigate the effect of transforming growth factor-beta1 (TGF beta1) on epithelial-mesenchymal transition in type II alveolar epithelial cells and the relationship with Calpain. METHODS: The type II alveolar epithelial cell line-A549 cells cultured in vitro were divided into 4 groups: the control group, the TGF-betal group, the TGF-beta1 + PD150606 group, the PD150606 group. Given the corresponding processing,Western-blot and RT-PCR were utilized to evaluate the expression of Calpain- 1,E-cad and alpha-SMA. RESULTS: Compared with the control group, the protein and mRNA expression of Calpain-1 and alpha-SMA in the TGF-beta1 group was markedly increased, but the protein and mRNA expression of E cad was significantly decreased. While, after calpain inhibitor PD150606 was added, the protein and mRNA expression of Calpain-1 and alpha-SMA was markedly decreased and the protein and mRNA expression of E-cad was significantly increased in the TGF-betal + PD150606 group, but there was no difference between TGF-beta1 + PD150606 group and control group. But with Calpain inhibitor PD150606 alone, the expression of Calpain-1,E-cad and alpha-SMA was no difference with the control group. CONCLUSIONS: TGF-betal could induce epithelial-mesenchymal transition in A549 cells by up-regulating expression of calpain which could be inhibited by calpain inhibitor PD150606. PMID- 26269312 TI - [Critical illness and diaphragm function]. PMID- 26269311 TI - [The timing and strategy of anticoagulant therapy in severe pneumonia]. PMID- 26269313 TI - [Noninvasive assisted ventilation in central and complex sleep apnea]. PMID- 26269314 TI - [Research progress of the role of oxidative stress in the pathogenesis of COPD]. PMID- 26269315 TI - The heart of medicine: growing up with pioneering treatment. PMID- 26269316 TI - Viral hepatitis surveillance and outbreak report is published in India. PMID- 26269318 TI - Histiocytoid neutrophilic dermatitis, an unusual histopathology in neonatal lupus erythematosus. AB - The authors reported histiocytoid neutrophilic dermatitis in neonatal lupus erythematosus (NLE). One-month-old male infant presented with annular erythematous plaques at the face and trunk. Serologic studies revealed positive anti-ribonuclear protein antibodies (RNP) and antinuclear antibodies (ANA). Histopathology showed predominant myeloid lineage mononuclear cells admixed with segmented neutrophils. This finding is uncommon in cutaneous NLE. Cutaneous NLE and LE should be included in the differential diagnosis of histiocytoid neutrophilic dermatitis. Additional immunohistochemistry studies with clinical and serologic correlations are important to differentiate histiocytoid neutrophilic dermatitis from the other diagnoses, especially leukemic cutis in young patients. PMID- 26269317 TI - First report of feline morbillivirus in Europe. AB - Feline morbillivirus was detected in urine samples of a 15 year old cat suffering from severe nephropathy. Viral RNA was not detected in blood and faecal samples and also the most common pathogens associated to cat kidney failure were not found. This report describes the first evidence of feline morbillivirus in Europe. PMID- 26269320 TI - Enhanced performance of dye-sensitized solar cells with dual-function coadsorbent: reducing the surface concentration of dye-iodine complexes concomitant with attenuated charge recombination. AB - In this paper, we have investigated the effects of oleic acid as a dual-function coadsorbent on recombination and iodine binding in dye-sensitized solar cells. Oleic acid as a dual-function coadsorbent effectively shields the back electron transfer from TiO2 to I3(-) ions and also reduces the surface concentration of dye-I2 complexes via iodine binding to the unsaturated double bond on oleic acid. It was found that interaction between iodine and the double bond of oleic acid keeps the iodine molecules away from the surface and reduces the recombination rate between injected electrons in a semiconductor and iodine molecules and also increases open-circuit voltage. Furthermore, the interaction between iodine molecules and unexcited dyes affects the UV-Vis spectrum of them and prevents an unfavorable blue shift. Overall, the results point to an improved performance for DSC operation and development. PMID- 26269321 TI - Spontaneous formation and amplification of an enantioenriched alpha-amino nitrile: a chiral precursor for Strecker amino acid synthesis. AB - Without the addition of any chiral substances, the spontaneous formation of an enantioenriched alpha-amino nitrile (up to 96% ee), which is a chiral precursor for Strecker amino acid synthesis, has been achieved in combination with conglomerate formation. The frequency of the formation of enantiomorphs exhibits an approximate stochastic distribution, i.e., L-form occurred 21 times and D-form occurred 22 times, which fulfils the conditions necessary for spontaneous absolute asymmetric synthesis. PMID- 26269319 TI - Enamel matrix derivative improves gingival fibroblast cell behavior cultured on titanium surfaces. AB - OBJECTIVE: Although an extensive amount of research has demonstrated the positive effects of an enamel matrix derivative (EMD) on soft tissue wound healing around intrabony defects, little information is available describing its effect on peri implant soft tissues, an area that has recently gained tremendous awareness due to the increasing prevalence of peri-implantitis. The aim of the present study was to assess the role of EMD when gingival fibroblasts were cultured on titanium surface with different surface topographies. METHODS: Human primary gingival fibroblasts were cultured on pickled (PT) and sand-blasted with large grit followed by acid etching (SLA) surfaces and assessed for cell adhesion at 2, 4, and 8 h, cell morphology at 2, 4, 8, and 24 h as well as cell proliferation at 1, 3, and 5 days post-seeding. Furthermore, genes encoding collagen 1a1, vascular endothelial growth factor-A (VEGF-A), and fibronectin were assessed by real-time PCR. Human gingival fibroblasts were also quantified for their ability to synthesize a collagen matrix on the various titanium surfaces with and without EMD by immunofluorescence staining. RESULTS: The results from the present study demonstrate that EMD significantly increased cell spreading at 2, 4, 8, and 24 h on PT surfaces and 4, 8, and 24 h on SLA surfaces. Furthermore, proliferation at 5 days on PT surfaces and 3 and 5 days on SLA surfaces was also increased for groups containing EMD. Real-time PCR results demonstrated that the culture of gingival fibroblasts with EMD significantly increased extracellular matrix synthesis of collagen 1 as well as improved mRNA levels of VEGF-A and fibronectin. Collagen1 immuno-fluorescent staining revealed a significantly higher area of staining for cells seeded on PT + EMD at 7 and 14 days and 14 days for SLA + EMD when compared to control samples. CONCLUSION: The results from the present study favor the use of EMD for colonization of gingival fibroblasts on titanium surfaces by increasing cell growth, spreading, and synthesis of an extracellular matrix. The improvements were primarily irrespective of surface topography. Future animal and human studies are necessary to fully characterize the beneficial effects of incorporating EMD during soft tissue regeneration of implant protocols. CLINICAL RELEVANCE: The use of EMD may speed up the quality of soft tissue integration around dental implants by facilitating gingival cell attachment, proliferation, and matrix synthesis of collagen 1. PMID- 26269322 TI - Ferroelectricity driven magnetism at domain walls in LaAlO3/PbTiO3 superlattices. AB - Charge dipole moment and spin moment rarely coexist in single-phase bulk materials except in some multiferroics. Despite the progress in the past decade, for most multiferroics their magnetoelectric performance remains poor due to the intrinsic exclusion between charge dipole and spin moment. As an alternative approach, the oxide heterostructures may evade the intrinsic limits in bulk materials and provide more attractive potential to realize the magnetoelectric functions. Here we perform a first-principles study on LaAlO3/PbTiO3 superlattices. Although neither of the components is magnetic, magnetic moments emerge at the ferroelectric domain walls of PbTiO3 in these superlattices. Such a twist between ferroelectric domain and local magnetic moment, not only manifests an interesting type of multiferroicity, but also is possible useful to pursuit the electrical-control of magnetism in nanoscale heterostructures. PMID- 26269323 TI - Teleconsultation for integrated palliative care at home: A qualitative study. AB - BACKGROUND: Interprofessional consultation contributes to symptom control for home-based palliative care patients and improves advance care planning. Distance and travel time, however, complicate the integration of primary care and specialist palliative care. Expert online audiovisual teleconsultations could be a method for integrating palliative care services. AIM: This study aims to describe (1) whether and how teleconsultation supports the integration of primary care, specialist palliative care, and patient perspectives and services and (2) how patients and (in)formal caregivers experience collaboration in a teleconsultation approach. DESIGN: This work consists of a qualitative study that utilizes long-term direct observations and in-depth interviews. SETTING/PARTICIPANTS: A total of 18 home-based palliative care patients (16 with cancer, 2 with chronic obstructive pulmonary disease; age range 24-85 years old), 12 hospital-based specialist palliative care team clinicians, and 17 primary care physicians. RESULTS: Analysis showed that the introduction of specialist palliative care team-patient teleconsultation led to collaboration between primary care physicians and specialist palliative care team clinicians in all 18 cases. In 17/18 cases, interprofessional contact was restricted to backstage work after teleconsultation. In one deviant case, both the patient and the professionals were simultaneously connected through teleconsultation. Two themes characterized integrated palliative care at home as a consequence of teleconsultation: (1) professionals defining responsibility and (2) building interprofessional rapport. CONCLUSION: Specialist palliative care team teleconsultation with home-based patients leads to collaboration between primary care physicians and hospital-based palliative care specialists. Due to cultural reasons, most collaboration was of a multidisciplinary character, strongly relying on organized backstage work. Interdisciplinary teleconsultations with real-time contact between patient and both professionals were less common but stimulated patient-centered care dialogues. PMID- 26269324 TI - The impact of a new public health approach to end-of-life care: A systematic review. AB - BACKGROUND: Communities play an increasingly significant role in their own health and social care, and evidence demonstrates the positive impact of this work on a range of health outcomes. Interest is building regarding the application of the principles of the new public health approach to those facing the end of life and their families and communities. AIM: To review the evidence relating to the impact of a new public health approach to end-of-life care, specifically as this applies to efforts to strengthen community action. DESIGN: A systematic review employing narrative synthesis. Both meta-ethnography and the use of descriptive statistics supported analysis. DATA SOURCES: Eight databases (AMED, ASSIA, BiblioMap, CINAHL, Cochrane Reviews, EMBASE, MEDLINE and PsycINFO) were searched from the earliest record to March 2015 using set eligibility criteria. RESULTS: Eight articles were included in the analysis. Three main themes emerged from the meta-ethnography: making a practical difference, individual learning and personal growth and developing community capacity. The quantitative findings mapped to the meta-ethnography and demonstrated that engaging communities can lead to improved outcomes for carers such as decreased fatigue or isolation, increase in size of caring networks and that wider social networks can influence factors such as place of death and involvement of palliative care services. CONCLUSION: Evidence exists for the impact of community engagement in end-of-life care. Impact assessment should be an integral part of future initiatives and policy makers should recognise that these approaches can influence complex issues such as carer support, community capacity, wellbeing and social isolation. PMID- 26269325 TI - Doctors discussing religion and spirituality: A systematic literature review. AB - BACKGROUND: Discussion of religion and/or spirituality in the medical consultation is desired by patients and known to be beneficial. However, it is infrequent. We aimed to identify why this is so. AIM: We set out to answer the following research questions: Do doctors report that they ask their patients about religion and/or spirituality and how do they do it? According to doctors, how often do patients raise the issue of religion and/or spirituality in consultation and how do doctors respond when they do? What are the known facilitators and barriers to doctors asking their patients about religion and/or spirituality? DESIGN: A mixed qualitative/quantitative review was conducted to identify studies exploring the physician's perspective on discussion of religion and/or spirituality in the medical consultation. DATA SOURCES: We searched nine databases from inception to January 2015 for original research papers reporting doctors' views on discussion of religion and/or spirituality in medical consultations. Papers were assessed for quality using QualSyst and results were reported using a measurement tool to assess systematic review guidelines. RESULTS: Overall, 61 eligible papers were identified, comprising over 20,044 physician reports. Religion and spirituality are discussed infrequently by physicians although frequency increases with terminal illness. Many physicians prefer chaplain referral to discussing religion and/or spirituality with patients themselves. Such discussions are facilitated by prior training and increased physician religiosity and spirituality. Insufficient time and training were the most frequently reported barriers. CONCLUSION: This review found that physician enquiry into the religion and/or spirituality of patients is inconsistent in frequency and nature and that in order to meet patient needs, barriers to discussion need to be overcome. PMID- 26269326 TI - Is there pain with neuropathic characteristics in patients with amyotrophic lateral sclerosis? A cross-sectional study. AB - BACKGROUND: Amyotrophic lateral sclerosis is a progressive debilitating and lethal disorder, characterized by degeneration of motor neurons that warrant palliative care. Pain is frequent in patients with amyotrophic lateral sclerosis and significantly impacts on quality of life. AIM: To describe pain and assess the prevalence of pain with neuropathic characteristics in patients with amyotrophic lateral sclerosis. DESIGN: Cross-sectional survey from March 2009 to October 2013. SETTING/PARTICIPANTS: Amyotrophic lateral sclerosis patients underwent multidisciplinary assessment and completed questionnaires measuring the severity and impact of pain and anxiety. The Douleur Neuropathique-4 questionnaire was used to look for pain with neuropathic characteristics. RESULTS: Of 96 clinical evaluations, 93 were usable for analysis (age at onset: 62 +/- 12.5 years; disease duration: 34 +/- 33 months). The overall pain prevalence was 66%, with 9% experiencing pain with neuropathic characteristics. Pain was most often located in the neck and shoulders (38% of pain patients). Neck and shoulder pain was associated with neck (p = 0.04) and proximal upper limb muscular weakness (p = 0.02), respectively. Pain was not associated with disease duration, respiratory or nutritional parameters, but with higher anxiety scores (p = 0.01). Patients with neuropathic characteristics pain did not differ significantly from patients with or without pain, except that they had higher minimal pain intensity score (p < 0.05). Neuropathic characteristics pain was frequently spontaneous (rarely evoked) and described as numbness, burning, electric shock, tingling, and pins-and-needle. CONCLUSION: Even if amyotrophic lateral sclerosis is a disease of the motor system, pain is frequent and can rarely have neuropathic characteristics. Pain must be always sought and appropriately treated to limit quality of life impairment. PMID- 26269327 TI - Application of chlorine-36 technique in determining the age of modern groundwater in the Al-Zulfi province, Saudi Arabia. AB - The present study aims to estimate the residence time of groundwater based on bomb-produced (36)Cl. (36)Cl/Cl ratios in the water samples are determined by inductively coupled plasma mass spectrometry and liquid scintillation counting. (36)Cl/Cl ratios in the groundwater were estimated to be 1.0-2.0 * 10(-12). Estimates of residence time were obtained by comparing the measured bomb-derived (36)Cl concentrations in groundwater with the background reference. Dating based on a (36)Cl bomb pulse may be more reliable and sensitive for groundwater recharged before 1975, back as far as the mid-1950s. The above (36)Cl background concentration was deduced by determining the background-corrected Dye-3 ice core data from the frozen Arctic data, according to the estimated total (36)Cl resources. The residence time of 7.81 * 10(4) y is obtained from extrapolated groundwater flow velocity. (36)Cl concentration in groundwater does not reflect the input of bomb pulse (36)Cl, and it belongs to the era before 1950. PMID- 26269328 TI - Microcystic pseudoglandular plexiform cutaneous neurofibroma. AB - Glandular structures are well documented to appear in peripheral nerve sheath tumors. These epithelial elements are usually present in malignant peripheral nerve sheath tumors although a few cases of glandular benign peripheral nerve sheath tumors have also been described, most of them being schwannomas. A neurofibroma with glands is considered to be a rare type of divergent differentiation, but a neurofibroma containing gland-like or pseudoglandular structures have not, to our knowledge, been described. We report a 33-year-old patient with a well-demarcated dermal neoplasm, composed of neoplastic Schwann cells, perineurial-like cells and fibroblasts in a matrix with collagen fibers and myxoid areas. A part of the tumor consisted of microcystic gland-like spaces lined by flat cells. These cells were either S100 positive or negative, with no epithelial membrane antigen, cytokeratin or CD31 immunostaining. Recognition of the presence of pseudoglandular elements in neurofibromas is important to distinguish them from other tumoral lesions, some of them with malignant potential. PMID- 26269329 TI - Time-efficient interleaved human (23)Na and (1)H data acquisition at 7 T. AB - The aim of this study was to implement and evaluate a flexible and time-efficient interleaved imaging approach for the acquisition of proton and sodium images of the human knee at 7 T within a clinically relevant timescale. A flexible software framework was established which allowed the interleaving of multiple, different, fully specific absorption ratio (SAR)-validated scans. The system was able to switch between these different scans at flexible time points. The practical example presented consists of interleaved proton (Dixon imaging and T2* mapping) and sodium (mapping the sodium content and fluid-suppressed component separately) sequences with the key idea to perform proton MRI whilst the sodium nuclei relax towards thermal equilibrium, and vice versa. Comparisons were made between these four scans being acquired sequentially in the normal mode of scanner operation and those acquired in an interleaved fashion. Images acquired in the interleaved mode were very similar to those acquired in sequential scans with no image artifacts produced by the slight intra-sequence variation in steady-state magnetization. A reduction in scanning time of almost a factor of two was established using the interleaved scans, allowing such a protocol to be completed within 30 min. Phantom experiments and in vivo scans performed in healthy volunteers and in one patient proved the basic feasibility of this approach. This approach for the interleaving of multiple proton and sodium scans, each with different contrasts, is an efficient method for the design of new practical clinical protocols for sodium MRI. PMID- 26269330 TI - Substrate-controlled product-selectivity in the reaction of the Bestmann-Ohira reagent with N-unprotected isatin-derived olefins. AB - A mild and efficient reaction of the Bestmann-Ohira reagent with N-unprotected isatin-derived olefins has been developed for the selective synthesis of spiro pyrazoline-oxindoles and tricyclic pyrazoles. The reaction features an attractive product-selectivity depending on the substituent on isatin-derived olefin. Treatment of 3-aryl/alkylideneoxindoles with BOR afforded spiropyrazoline oxindoles, whereas 3-phenacylideneoxindoles furnished pyrazoloquinazolinones via a unique ring expansion reaction. PMID- 26269331 TI - Expression profiles uncover the correlation of OPN signaling pathways with rat liver regeneration at cellular level. AB - Osteopontin (OPN) could participate in the occurrence of multiple liver diseases via promoting inflammation, cell activation, proliferation, and migration. However, the correlation of OPN with liver regeneration (LR) is poorly defined. Previous studies from us and others revealed that OPN was probably involved in the activation and proliferation of various hepatic cell types during LR. In this study, to further investigate the underlined mechanism of OPN in regulating LR, eight hepatic cell types were isolated and purified from rat regenerative livers at 10 time points. The gene expression profiles of above hepatic cells were assayed by Rat Genome 230 2.0 chips, and then IPA software was used to uncover the correlations of gene expression changes with physiological activities. The findings demonstrated that the majority of the OPN pathway-related genes were up regulated in hepatocytes (HCs), pit cells (PCs), oval cells (OCs), and biliary epithelial cells (BECs) but down-regulated in other four cell types including sinusoidal endothelial cells (SECs), Kupffer cells (KCs), dendritic cells (DCs), and hepatic stellate cells (HSCs). Thereafter, functional enriched analysis by IPA indicated that OPN signaling pathway might promote cell proliferation, activation, migration, and inflammation in HCs, OCs, BECs, and PCs, and slightly boost proliferation and migration of SECs and KCs but inhibit inflammation response and chemotaxis in SECs and KCs and almost all physiological processes in DCs and HSCs. Morever, apoptosis, cell death, and necrosis were remarkably inhibited through JAK/STAT, ERK1/2, and NF-kB branches in almost every cell type. These above results suggest that OPN signaling pathway is closely related to HCs, OCs, BECs, and PCs but has less regulatory effect on SECs, KCs, HSCs, and DCs during rat LR. PMID- 26269334 TI - [Heart rate is a new druggable target in the individualized management of patients with chronic heart failure]. PMID- 26269333 TI - Galaxy Integrated Omics: Web-based Standards-Compliant Workflows for Proteomics Informed by Transcriptomics. AB - With the recent advent of RNA-seq technology the proteomics community has begun to generate sample-specific protein databases for peptide and protein identification, an approach we call proteomics informed by transcriptomics (PIT). This approach has gained a lot of interest, particularly among researchers who work with nonmodel organisms or with particularly dynamic proteomes such as those observed in developmental biology and host-pathogen studies. PIT has been shown to improve coverage of known proteins, and to reveal potential novel gene products. However, many groups are impeded in their use of PIT by the complexity of the required data analysis. Necessarily, this analysis requires complex integration of a number of different software tools from at least two different communities, and because PIT has a range of biological applications a single software pipeline is not suitable for all use cases. To overcome these problems, we have created GIO, a software system that uses the well-established Galaxy platform to make PIT analysis available to the typical bench scientist via a simple web interface. Within GIO we provide workflows for four common use cases: a standard search against a reference proteome; PIT protein identification without a reference genome; PIT protein identification using a genome guide; and PIT genome annotation. These workflows comprise individual tools that can be reconfigured and rearranged within the web interface to create new workflows to support additional use cases. PMID- 26269332 TI - The Human Tau Interactome: Binding to the Ribonucleoproteome, and Impaired Binding of the Proline-to-Leucine Mutant at Position 301 (P301L) to Chaperones and the Proteasome. AB - The tau protein is central to the etiology of several neurodegenerative diseases, including Alzheimer's disease, a subset of frontotemporal dementias, progressive supranuclear palsy and dementia following traumatic brain injury, yet the proteins it interacts with have not been studied using a systematic discovery approach. Here we employed mild in vivo crosslinking, isobaric labeling, and tandem mass spectrometry to characterize molecular interactions of human tau in a neuroblastoma cell model. The study revealed a robust association of tau with the ribonucleoproteome, including major protein complexes involved in RNA processing and translation, and documented binding of tau to several heat shock proteins, the proteasome and microtubule-associated proteins. Follow-up experiments determined the relative contribution of cellular RNA to the tau interactome and mapped interactions to N- or C-terminal tau domains. We further document that expression of P301L mutant tau disrupts interactions of the C-terminal half of tau with heat shock proteins and the proteasome. The data are consistent with a model whereby a higher propensity of P301L mutant tau to aggregate may reflect a perturbation of its chaperone-assisted stabilization and proteasome-dependent degradation. Finally, using a global proteomics approach, we show that heterologous expression of a tau construct that lacks the C-terminal domain, including the microtubule binding domain, does not cause a discernible shift of the proteome except for a significant direct correlation of steady-state levels of tau and cystatin B. PMID- 26269335 TI - [Heart rate reduction is not the therapeutic target in the chronic heart failure therapy]. PMID- 26269336 TI - [Loop diuretic strategies in patients with heart failure]. PMID- 26269337 TI - [Compliance to treatment and resistant hypertension]. PMID- 26269338 TI - [Peak oxygen consumption, NT-proBNP and echocardiographic changes in patients with chronic heart failure]. AB - OBJECTIVE: To assess peak oxygen consumption (peak VO2) derived from cardiopulmonary exercise testing (CPET), concentrations of NT-proBNP and echocardiographic changes in patients with chronic heart failure (CHF) and reduced left ventricular ejection fraction (LVEF, <40%). METHODS: Seventy patients were included and divided into two groups according to the New York Heart Association (NYHA) classification: NYHA II group (17 cases) and NYHA III-IV group (53 cases). The basic clinical information, plasma concentration of NT proBNP at rest, echocardiographic parameters and peak VO2from CPET were compared between two groups. Correlation among peak VO2, NT-proBNP and echocardiographic parameters in this patient cohort was assessed and their abilities to discriminate the NYHA III-IV grade were analyzed through c-Statistic. RESULTS: Left atrial diameter ((51.3 +/- 7.2) mm vs. (44.0+/-7.4) mm, P<0.001) was larger, plasma concentration of NT-proBNP (1 379-4 399 pmol/L vs. 1 109-2 356 pmol/L, P<0.01) was higher and peak VO2((13.4 +/- 3.5) ml.kg-1.min-1 vs. (18.2 +/- 3.7) ml.kg-1.min-1, P<0.001) were significantly lower in NYHA III-IV group than those in NYHA II group. However, left ventricular end-diastolic diameter (LVEDD) and LVEF were similar between two groups. Peak VO2correlated significantly with NT proBNP (r=-0.311, P<0.01), but neither peak VO2nor NT-proBNP correlated with echocardiographic parameters (LA, LVEDD and LVEF). ROC analysis showed that peak VO2had the strongest discriminatory power for detecting NYHA III-IV grade patients (AUC=0.835, P<0.001), followed by the NT-proBNP (AUC=0.723, P<0.01). CONCLUSION: Peak VO2is a more sensitive parameter to detect the disease aggravation (NYHA III-IV grade) of the CHF patients with reduced LVEF compared to plasma NT-proBNP and echocardiographic parameters (LA, LVEDD, LVEF). PMID- 26269340 TI - [Impact of transfection with recombinant adenovirus vector-mediated Klotho gene on myocardial remodeling in a rat model of heart failure]. AB - OBJECTIVE: To assess the impact of transfection with recombinant adenovirus vector-mediated Klotho gene on myocardial remodeling in a rat model of heart failure (HF) by intraperitoneal injection of isoproterenol. METHODS: Rats were divided into 5 groups by table of exponential random numbers: normal control group, HF group, saline-control HF group, recombinant adenovirus vector transfection group (Ad.EGFP group, 2 * 1010 pfu, 0.5 ml/rat), pDC316-CMV-EGFP rKlotho transfection group (Ad.Klotho group, n=5 each). Left ventricular ejection fraction (LVEF) was obtained by echocardiography, hemodynamic parameters obtained by multi-channel physiological recorder, myocardial tissue underwent pathohistological examination. Additionally, the green fluorescin expression was observed on frozen heart section. Myocardial fibrosis correlated gene expression including Klotho gene, collagen I and III was detected by real time-PCR. Moreover, plasma levels of B-type natriuretic peptide (BNP) were measured with ELISA. RESULTS: Compared to saline control HF group, LVEF, LVSP and +/-dp/dtmax were significantly increased, myocardial fibrosis and myocardial remodeling were significantly attenuated in the Ad. Klotho group and there was green fluorescin distribution in myocardial tissues of Ad. Klotho group. Klotho expression was down-regulated and collagen I and III expression was upregulated in HF rats compared to normal control group (all P<0.05) and these changes could be significantly reversed in Ad. Klotho group (all P<0.05). Plasma BNP level was also significantly lower in Ad. Klotho group than in HF group (P<0.05). CONCLUSIONS: Klotho gene transfection could improve cardiac function and attenuate cardiac remodeling and reducing myocardial fibrosis. PMID- 26269339 TI - [2-Methylthio-adenosine-5'-triphosphate inhibits ventricular arrhythmogenesis in rabbits with chronic heart failure]. AB - OBJECTIVE: To investigate the effects and related mechanisms of 2-methylthio adenosine-5'-triphosphate (2-MeSATP), an important extracellular agonist that activates receptors for purine nucleotides (P2XR), on ventricular arrhythmias in rabbits with chronic heart failure (CHF). METHODS: The male New Zealand rabbits were divide into control (n=12), CHF (n=12) and CHF+2-MeSATP groups (2-MeSATP, n=12). CHF was induced by isoproterenol injection (0.3 mg.kg-1.d-1 for 3 weeks) and rabbits were observed 6 months later. The main cardioelectrophysiological parameters and ventricular arrhythmias were tested by recording monophasic action potential (MAP) with burst-pacing (BCL) in rabbits in vivo. The transient outward potassium current (Ito) was recorded via whole-cell patch clamp technique and the fluorescence intensity of intracellular free Ca2+ was detected with Flup-3/AM loading by the laser scanning confocal microscope in enzymatically dissociated single rabbet ventricular myocytes. RESULTS: CHF rabbits developed severely clinical CHF signs and symptoms, reduced left ventricular ejection fraction and fractional shortening as well as enlarged end-diastolic dimension. Compared with CHF group, APA and MaxdV/dt were significantly increased, while APD20, APD50 and APD90 were significantly reduced in 2-MeSATP group (all P<0.01). Moreover, 2 MeSATP could obviously shorten BCL induced ventricular arrhythmias, and decrease deducibility and persistence time of ventricular arrhythmias with burst-pacing in 2-MeSATP group in vivo (all P<0.05). With voltage clamp model, 2-MeSATP could significantly increase the current density of Ito in different command potential in CHF ventricular myocytes (all P<0.01). When holding potential was set at -50 mV and command potential was set at +50 mV, the current densities of Ito increase was more significant in 2-MeSATP group than that in CHF group ((11.79 +/- 4.51) pA/pF vs. (7.94 +/- 3.53) pA/pF, P<0.01). 2-MeSATP could completely change the I V curve upward without changing the I-V curve direction in CHF ventricular myocytes. The fluorescence intensities of intracellular free Ca2+ increase was more significant in 2-MeSATP group compared to CHF group ((1 291.98 +/- 123.31) umol/L vs. (793.59 +/- 114.65) umol/L, P<0.01). CONCLUSION: 2-MeSATP as a potent agonist acting on P2XR could significantly shorten APD, increase heart rate and improve cardiac performance as well as decrease the susceptibility of ventricular arrhythmias in this rabbit CHF model. Our results suggest that Ito increase and sarcoplasmic reticulum uptake Ca2+ enhancement as well as dynamic balance of intracellular Ca2+ cycling sustenance might linked to the beneficial effects of 2 MeSATP in this CHF model. PMID- 26269341 TI - [Current status and influence factors of beta blocker prescription in Chinese patients with stable angina pectoris]. AB - OBJECTIVE: To analyze the status of beta blockers (BBs) prescription in Chinese patients with stable angina pectoris. To determine the gap between clinical practice and treatment guidelines and factors influencing the use of BBs in Chinese patients. METHOD: A questionnaire survey was conducted in patients diagnosed with chronic stable angina pectoris in 2011. A total of 298 Chinese hospitals attended the survey. The questionnaire collected patient demographic information, clinical and medication information. In the analysis, patients were divided into two groups according to whether they were on BBs at the time of the interview. Hospital characteristics, patient demographic information, cardiovascular risk factors, diagnostic method of coronary heart disease, past history of coronary revascularization and use of secondary prevention medications were compared between the two groups. Binary logistic regression analysis was used to identify factors related to BBs use. Patients were followed-up for 3 months. Patients who were on BBs at baseline were divided into two groups according to whether they were still on BBs after 3 months. Comparison of the clinical information previously mentioned was made between the two groups, and binary logistic regression analysis was used to identify factors related to BBs adherence. RESULTS: Of the 5 011 questionnaires, 2 859 cases were male, mean age was (67.6 +/- 11.5) years old, 3 060 (61.1%) patients were on BBs at baseline. Binary logistic regression analysis showed that when adjusted for other factors, old age (OR = 0.895, 95% CI 0.849-0.944, P<0.001) was related to no BBs use, while comorbidity with hypertension (OR = 1.255, 95% CI 1.103-1.427, P = 0.001) or hyperlipidemia (OR = 1.456, 95% CI 1.287-1.648, P<0.001), diagnosed with coronary disease by imaging (OR = 1.250, 95% CI 1.070-1.461, P = 0.005) and past history of coronary revascularization (OR = 1.490, 95% CI 1.220-1.820, P<0.001) were related to higher percentage of BBs use. A total of 2 533 cases (82.8%) were still taking BBs 3 months after baseline interview. Binary logistic regression analysis showed that, when adjusted for other factors, treated at traditional Chinese medical hospitals (OR = 1.612, 95% CI 1.154-2.251, P = 0.005), low levels of education (OR = 1.316, 95% CI 1.151-1.504, P<0.001), hypertension (OR = 1.345, 95% CI 1.096-1.651, P = 0.005), high baseline heart rate (OR = 1.020, 95% CI 1.010-1.030, P<0.001) and diagnosed with coronary disease by imaging (OR = 1.342, 95% CI 1.095-1.644, P = 0.005) were factors related to higher BBs adherence, while low baseline CCS class (OR = 0.794, 95% CI 0.704-0.896, P<0.001) was related to lower BBs adherence. CONCLUSIONS: In Chinese patients with clinically diagnosed chronic stable angina, BBs use was not sufficient. Old age, comorbidity with hypertension or hyperlipidemia, past history of coronary revascularization were independently related to higher percentage of BBs use. Treated at traditional Chinese medical hospitals, low levels of education, hypertension, high baseline heart rate and diagnosed with coronary disease by imaging were independent factors related to higher BBs adherence, while low baseline CCS class was related to lower adherence. PMID- 26269342 TI - [Application feasibility of low tube voltage and lower iodine concentration contrast medium as well as iterative reconstruction in coronary computed tomography angiography]. AB - OBJECTIVE: To investigate the feasibility of using lower iodine concentration (270 mgI/ml) contrast medium, lower X-ray tube voltage (100 kVp) and iterative reconstruction (IR) to reduce both iodine load and radiation dose but keep the image quality of coronary CT angiography (CCTA). METHODS: A total of 80 consecutive patients with suspected coronary artery disease were prospectively assigned to one of two groups via computer central system from January to May 2013. The control group (n = 40) was scanned using dual-source CCTA protocols of 120 kV, 370 mgI/ml Iopromide and filtered back projection reconstruction with a vascular algorithm (B26f). The study group (n = 40) was scanned using 100 kV, 270 mgI/ml Iodixanol and sinogram affirmed iterative reconstruction with a vascular algorithm (I26f). Other scan parameters and contrast injection protocol were similar between the two groups. Attenuation in the ascending aorta and coronary arteries along with image noise were measured. Images were reconstructed, measured and graded, and iodine load and effective radiation dose were calculated. RESULTS: The body mass index ((25.3 +/- 3.0) kg/m2 vs. (25.4 +/- 3.0)kg/m2, P = 0.852), image quality scores (4.70 +/- 0.52 vs. 4.63 +/- 0.59, P = 0.545), mean signal-to-noise ratios (22.2 +/- 5.5 vs. 23.6 +/- 5.8, P = 0.277), and contrast-to-noise ratios (35.6 +/- 17.6 vs. 41.1 +/- 17.6, P = 0.163) were similar between the control group and study group. Mean iodine loads were significantly reduced in the study group ((18.49 +/- 0.75)g) compared to control group ((25.27 +/- 0.94)g), P< 0.001). Mean effective radiation doses were also significantly reduced in the study group ((2.31 +/- 0.73) mSv) compared to that in control group ((3.52 +/- 1.16) mSv), P< 0.001). CONCLUSION: Use of low X-ray tube voltage and iterative reconstruction allows lower iodine load and effective radiation dose application at CCTA without image quality reduction. PMID- 26269343 TI - [Association between body mass index and cardiovascular events in male elderly hypertensive patients]. AB - OBJECTIVE: To observe the long-term relationship between body mass index (BMI) and cardiovascular events in male elderly hypertensive patients. METHODS: A total of 839 male elderly (>65 years old) hypertensive patients were included in this prospective study. Baseline data were obtained on January 2004 and participants were followed up yearly till January 2014. Patients were divided into 3 groups according to their BMI: normal weight group (18.5 kg/m2 <= BMI<24.0 kg/2), overweight group (24.0 kg/m2 <= BMI<28.0 kg/m2), obese group (BMI >= 28.0 kg/m2). All-cause death and cardiovascular events were compared. RESULTS: The average age of all 839 hypertension men was (75.4 +/- 4.8) years at baseline. Baseline systolic blood pressure was (133.7 +/- 14.6) mmHg (1 mmHg=0.133 kPa), diastolic blood pressure was (74.3 +/- 9.3)mmHg. Baseline systolic and diastolic blood pressure was similar among the three groups. All 839 patients completed follow up. There were 178 all-cause deaths, 54 cardiovascular deaths, 51 new/recurrent myocardial infarctions and 105 new/recurrent strokes during follow up. Incidence of all-cause mortality in overweight group (16.74%,72/430) was significantly lower than in normal weight group (27.01% (74/274), P<0.05). Kaplan-Meier curves showed the all-cause mortality and cardiovascular mortality were higher in normal weight group than in the other two groups. According to the Cox proportional hazards regression model, the risk of all-cause mortality (RR=0.867, 95% CI: 0.792-0.949) and cardiovascular death (RR=0.179, 95% CI : 0.05-0.645) in patients with a BMI >= 24.0 kg/m2 were lower than in the group with BMI<24.0 kg/m2. CONCLUSION: Obesity paradox phenomenon is observed in elderly male hypertensive patients in that higher BMI is associated with lower mortality risks in elderly male hypertensive patients during the 10 years follow-up. PMID- 26269344 TI - [Prevalence and echocardiographic feature of bicuspid aortic valve in patients with severe aortic stenosis: a echocardiography database analysis]. AB - OBJECTIVE: To evaluate the accuracy of echocardiography in identifying aortic valve structures and determine the prevalence of bicuspid aortic valves (BAV) in severe aortic stenosis (AS) population to provide useful information for transcatheteraortic valve replacement (TAVR). METHODS: A total of 300 AS patients undergoing surgical aortic valve replacement were included to determine the accuracy of transthoracic echocardiography in indentifying BAV from January 2009 to July 2013. The echocardiographic data of our hospital from 2004 to 2012 was retrospectively reviewed. 1 371 patients with isolated severe native aortic valves stenosis were consecutively enrolled. RESULTS: The aortic valve structures could be defined by transthoracic echocardiography in 75.7% (227/300) patients with severe AS. With BAV diagnosis during operation as gold standard, the accuracy of transthoracic echocardiography in identifying BAV was 89.4% (203/227). Among 1 371 patients with severe AS, the percentage of BAV in patients aged <40 years, aged 40-59 years, aged 60-69 years, aged 70-79 years and aged >= 80 years was 60.0% (57/95), 57.5% (262/456), 42.7% (184/431), 43.2% (133/308) and 21.0% (17/81), respectively. Incidence of BAV in patients with degenerative calcific valve was significant higher than in those with rheumatic heart disease (44.3% (552/1 246) vs. 4.0% (3/76), P<0.01). Proportion of combined aortic regurgitation >= grade 2 was significantly lower, ascending aortic diameter was larger and left ventricular end-diastolic dimension was smaller in BAV patients compared to severe AS patients with tricuspid valves (all P<0.01), while aortic valve annuals diameter and accompanying cardiovascular diseases between BAV and tricuspid aortic valve groups were similar (all P>0.05). CONCLUSIONS: Transthoracic echocardiography could accurately identify aortic valve structures in about 76% patients. BAV is common in severe AS patients across all ages. These results provide important information for the popularization of TVAR. PMID- 26269345 TI - [Role of NF-kappaB/survivin signal pathway on intima hyperplasia of rat carotid balloon injury restenosis model]. AB - OBJECTIVE: To investigate the role of NF-kappaB/survivin signal pathway in the intima hyperplasia of rat carotid balloon injury restenosis model. METHODS: NF kappaB siRNA lentivirus vector (titer was 1 * 108 TU/ml) was established. Carotid balloon injury restenosis model was made in 33 SD rats. The rats were divided into 4 groups according to different processing methods, including negative control (NC) group (n = 11), NF-kappaB siRNA group (n =11), NF-kappaB siRNA+YM155 (survivin inhibitor) (n = 11), the uninjured carotid artery served as the normal control group (n = 11). After 7 days, the carotid sample (n = 5 each group) were harvested to detect the NF-kappaB and survivin mRNA expression by RT-PCR.The carotid sample were harvested on 28 days (n = 6 each group) for HE staining and measuring intima hyperplasia. Immunohistochemical method was also used to detect the expression of intima proliferation cell nuclear antigen (PCNA) and media alpha-SM-actin. RESULTS: (1) After 7 days, NF-kappaB and survivin mRNA expression was significant higher in NC group than in normal control group (P<0.05), the NF kappaB mRNA expression was significantly lower in NF-kappaB siRNA group than in NC group (P<0.05) and similar between NF-kappaB siRNA group and NF-kappaB siRNA+YM155 group. The survivin mRNA expression was significantly lower in NF kappaB siRNA group compared to NC group (P<0.05) and significantly higher in NF kappaB siRNA group than in NF-kappaB siRNA+YM155 group (P<0.05). (2) After 28 days, intima hyperplasia was observed in NC (0.13 +/- 0.01), NF-kappaB siRNA (0.11 +/- 0.01) and NF-kappaB siRNA+YM155 group (0.09 +/- 0.01) mm2 (P<0.05). Media area was similar among NC group, NF-kappaB siRNA group and NF-kappaB siRNA+YM155 group (P>0.05). I/M ratio was gradually reduced among NC group (1.55 +/- 0.07), NF-kappaB siRNA group (0.92 +/- 0.08), NF-kappaB siRNA+YM155 group (0.76 +/- 0.06, all P<0.05). Similar results were found in the residual restenosis rate: NC group (58.71 +/- 0.02) %, NF-kappaB siRNA group (32.13 +/- 0.05) %, NF-kappaB siRNA+YM155 group (26.42 +/- 0.03) % (all P<0.05) and expression of vascular smooth muscle cell PCNA: NC group (45.32 +/- 7.21) %, NF kappaB siRNA group (36.54 +/- 6.42) %, NF-kappaB siRNA+YM155 group (28.57 +/- 6.31) % (all P<0.05). On the contrary, the IOD of alpha-SM-actin in media increased gradually: NC group (0.055 +/- 0.006), NF-kappaB siRNA group (0.072 +/- 0.011), NF-kappaB siRNA+YM155 group (0.084 +/- 0.008, all P<0.05). CONCLUSION: Inhibiting NF-kappaB expression can significant decrease intima hyperplasia in this model, and this effect may be mediated by inhibiting survivin and reducing the proliferation of vascular smooth muscle cells. PMID- 26269346 TI - [Angiotensin II induced myocardial hypertrophy in neonatal rats could be attenuated by activated kappa-opioid receptor via modulating the calcineurin signal pathways]. AB - OBJECTIVE: To observe the effect of kappa-opioid receptor (kappa-OR) stimulation on Angiotensin II (Ang II)-induced cardiomyocyte hypertrophy in vitro cultured myocardial cells from neonatal rats and on calcineurin (CaN) signal pathways. METHODS: Cultured myocardial cells of neonatal rats were divided into control group, CSA (1 umol/L) group, Ang II (1 umol/L) group, Ang II (1 umol/L) + U50488H (1 umol/L) group, Ang II (1 umol/L) + CSA (1 umol/L) group, Ang II (1 umol/L) + Rp-cAMPS (1 umol/L) group, Ang II (1 umol/L) + CSA (1 umol/L) + U50488H (1 umol/L) group and Ang II (1 umol/L) + PTX5 mg/L + U50488H (1 umol/L) group. The hypertrophic myocytes were induced by Ang II 1umol/L before kappa-OR agonist U50488H 1 umol/L was administered. The antihypertrophic effect of kappa-OR stimulation was observed in the presence of ciclosporine A (CsA) 1 umol/L, cAMP triethyl-ammonium salt (Rp-cAMPS) 1 umol/L, and pertussistoxin ( PTX) 5 mg/L. The total protein content was assayed by the method of Lowry. The [Ca2+]i was measured by confocal microscope using Fluo-3/AM as flouresecent indicator. The relative expression of CaN was determined by Western blot. RESULTS: (1) The total protein content of Ang II group was significantly higher than that in control group (P<0.01), which could be equally reduced by cotreatment with U50488H, CSA and Rp-cAMPS (P<0.01). Total protein content of the Ang II + PTX + U50488H group and the Ang II group was similar. (2) The [Ca2+]i was significantly higher in Ang II group of neonatal rat cardiomyocytes than that in control group (P<0.01), which could be reduced by cotreatment with U50488H, CSA and Rp-cAMPS (P<0.01). [Ca(2+)]i was similar between the Ang II + PTX + U50488H group and the Ang II group. (3) The expression of CaN was significantly higher in Ang II group than that in control group (P<0.01), which could be significantly reduced by cotreatment with U50488H, CSA and Rp-cAMPS (P<0.01). CaN was similar between the Ang II + PTX + U50488H group and the Ang II group. CONCLUSION: kappa-opioid receptor activation could attenuate Ang II induced cardiomyocytes hypertrophy via reducing [Ca2+]i and downreglating CaN. PMID- 26269347 TI - [Liraglutide attenuates myocardial ischemia/reperfusion injury possibly through reducing cardiomyocytes apoptosis and oxidation in rats]. AB - OBJECTIVE: To explore the effect of liraglutide on myocardial ischemia/reperfusion (I/R) injury in rats and related mechanisms. METHODS: Twenty four male SD rats were divided into sham group, I/R injury group, and liraglutide group by table of random number (n = 8 each). Myocardial I/R injury model was established by occlusion of the left anterior descending artery for 30 min followed by 2 h of reperfusion. HE stain method was used to observe cardiomyocyte status under light microscope, myocardial tissue samples were stained with TTC to measure the myocardial infarction size, protein expression of p53 and caspase-3 was analyzed by immunohistochemical technique and Western blot respectively, xanthine oxidase method was used to detect SOD activity, Thiobarbituric acid method was used to measure the concentration of MDA. RESULTS: Compared with the I/R group, the degree of myocardial damage of liraglutide group was significantly reduced and the myocardial infarct area was significantly lower ((44 +/- 8) % vs. (62 +/- 8) %, P<0.05) while protein expression of caspase-3 and p53 in liraglutide group was significantly downregulated (0.19 +/- 0.03 vs. 0.24 +/- 0.02 and 0.27 +/- 0.03 vs. 0.39 +/- 0.04, P<0.05). SOD activity was significantly increased and MDA concentration was significantly decreased (74.20 +/- 11.10 vs. 44.04 +/- 14.30 and 4.41 +/- 1.07 vs. 8.72 +/- 2.20, P<0.05) in liraglutide group compared to I/R group. CONCLUSION: Liraglutide protects myocardium against I/R injury possibly through reducing cardiomyocytes apoptosis and oxidation. PMID- 26269348 TI - [Value of neutrophils/lymphocytes ratio on predicting the prognosis of patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention:a meta-analysis]. AB - OBJECTIVE: To analyze the value of neutrophils/lymphocytes ratio (NLR) on predicting the cardiovascular events at hospital discharge and >= 12 months follow-up for patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) by meta-analysis. METHODS: Both English and Chinese databases, including PubMed, EMBASE, Wanfang database from their reception to June 2014 were searched to identify randomized controlled studies or non-randomized controlled studies that reported relationship between NLR and the prognosis of patients with STEMI undergoing PCI.The Newcastle OttawaScale (NOS) system was employed to assess the quality of literatures enrolled in this study. Two reviewers assessed the quality of each trial and extracted data independently. A standardized form and RevMan 5.2 software were used to extract information, and perform quantitative analysis, respectively. RESULTS: A total of 1 953 patients from 6 clinical trials were included in this meta-analysis. The risks of all-cause mortality (RR:0.29, 95% CI: 0.19-0.46, P<0.001), major adverse cardiac events (RR: 0.38, 95% CI: 0.31-0.46, P<0.001), nonfatal myocardial infarction (RR: 0.43, 95% CI: 0.28-0.67, P<0.001), stent thrombosis (RR: 0.32, 95% CI: 0.19-0.53, P<0.001), and TIMI flow after PCI procedure < 3 grade (RR: 0.34, 95% CI: 0.14-0.86, P = 0.020) were significantly lower in patients with NLR <= 3.30 compared patients with NLR > 3.30 at hospital discharge. During >= 12 months follow-up, the risks of death (RR: 0.33, 95% CI: 0.23-0.45, P<0.001), major adverse cardiac events (RR: 0.27, 95% CI: 0.20-0.35, P < 0.001) were significantly lower. Whereas nonfatal myocardial infarction was not significantly different (RR: 0.42, 95% CI: 0.05-3.45, P = 0.420) in patients with NLR <= 3.30 compared patients with NLR > 3.30. CONCLUSIONS: Results from this meta-analysis show that the NLR could predict short- and long-term prognosis in patients with STEMI undergoing PCI. This finding needs to be validated by large scale clinical trials in the future. PMID- 26269349 TI - [Successful defibrillation by an implantable cardioverter-defibrillator in a patient with high defibrillation threshold]. PMID- 26269350 TI - [Experience of fractional flow reserve and microcirculatory resistance index guided therapy in a patient with chest pain]. PMID- 26269351 TI - [Left ventricular apical hypoplasia complicated with right ventricular outflow tract obstruction: a case report]. PMID- 26269352 TI - [Research progress on signal transduction mechanisms of physiological and pathological cardiac hypertrophy]. PMID- 26269353 TI - [Research progress on the role of Th17 and Treg in the pathogenesis of various cardiovascular diseases]. PMID- 26269354 TI - [Update on the role of cardiomyocyte autophagy in the pathogenesis of ventricular remodeling]. PMID- 26269355 TI - The Mechanism of Reflection Type Reentry: A Simulation Study. AB - INTRODUCTION: Reflection is a special type of reentry in which an electrical wave front travels in a forward direction through tissue that is then re-excited by a wave front that propagates backward. This type of reentry has been studied computationally in 1-dimensional fibers and verified experimentally. Different hypotheses explaining reflected reentry have been proposed based on the structure and heterogeneity of the tissue properties, but the mechanism remains uncertain. METHODS AND RESULTS: We used the bidomain model to represent cardiac tissue and the Luo-Rudy model to describe the active membrane properties. We consider an ischemic region in a volume of ventricular myocardium. Our results show that a slow depolarization in the ischemic border zone caused by electrotonic coupling to depolarized tissue in the normal region creates a delay between proximal and distal regions that produces enough electrotonic current in the distal region to re-excite the proximal region. CONCLUSION: Our simulation shows that an early afterdepolarization (EAD) is not the source of the reflection. It depends on the pacing interval and stimulus strength necessary to maintain enough time delay between proximal and distal regions. PMID- 26269356 TI - Photophysical Studies on Covalently-linked Naphthalene and TEMPO Free Radical Systems: Observation of a Charge Transfer State in the Ground State. AB - A series of molecules containing a naphthalene chromophore and a stable free radical 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) covalently linked by a spacer group of different lengths have been synthesized. In n-hexane solution, their photophysical behavior was studied and compared with a system of freely moving naphthalene and the free radical TEMPO. The linked molecules showed strong quenching of the singlet and triplet states of the naphthalene moiety, compared to when naphthalene and TEMPO were not linked. The quenching efficiency decreased with increasing the length of the spacer group. In addition, new electronic absorption and emission bands, along with the usual bands of the individual moieties, were also seen. These news bands have been attributed to the formation of electron donor-acceptor charge-transfer complexes in the ground state, arising from the interaction between the two moieties in close proximity. The photophysical dynamics of the linked molecules has been rationalized by assuming the existence of two types of population of the linked molecules: folded and extended. The ground state complex formation is proposed to occur only in the folded conformation of the linked molecules. To our knowledge, this is possibly the first example of a ground state charge-transfer complex formation involving a TEMPO free radical and naphthalene. PMID- 26269357 TI - Curcumin analogues as selective fluorescence imaging probes for brown adipose tissue and monitoring browning. AB - Manipulation of brown adipose tissue (BAT) and browning of white adipose tissue (WAT) can be promising new approaches to counter metabolic disorder diseases in humans. Imaging probes that could consistently monitor BAT mass and browning of WAT are highly desirable. In the course of our imaging probe screening, we found that BAT could be imaged with curcumin analogues in mice. However, the poor BAT selectivity over WAT and short emissions of the lead probes promoted further lead optimization. Limited uptake mechanism studies suggested that CD36/FAT (fatty acid transporter) probably contributed to the facilitated uptake of the probes. By increasing the stereo-hindrance of the lead compound, we designed CRANAD-29 to extend the emission and increase the facilitated uptake, thus increasing its BAT selectivity. Our data demonstrated that CRANAD-29 had significantly improved selectivity for BAT over WAT, and could be used for imaging BAT mass change in a streptozotocin-induced diabetic mouse model, as well as for monitoring BAT activation under cold exposure. In addition, CRANAD-29 could be used for monitoring the browning of subcutaneous WAT (sWAT) induced by beta3-adrenoceptor agonist CL-316, 243. PMID- 26269360 TI - In patients with persistent atrial fibrillation complex ablation techniques were no better than pulmonary vein isolation alone in preventing recurrent atrial fibrillation. PMID- 26269358 TI - Berardinelli-Seip congenital lipodystrophy 2 regulates adipocyte lipolysis, browning, and energy balance in adult animals. AB - Mutations in BSCL2/SEIPIN cause Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2), but the mechanisms whereby Bscl2 regulates adipose tissue function are unclear. Here, we generated adipose tissue (mature) Bscl2 knockout (Ad-mKO) mice, in which Bscl2 was specifically ablated in adipocytes of adult animals, to investigate the impact of acquired Bscl2 deletion on adipose tissue function and energy balance. Ad-mKO mice displayed reduced adiposity and were protected against high fat diet-induced obesity, but not insulin resistance or hepatic steatosis. Gene expression profiling and biochemical assays revealed increased lipolysis and fatty acid oxidation in white adipose tissue (WAT) and brown adipose tissue , as well as browning of WAT, owing to induction of cAMP/protein kinase A signaling upon Bscl2 deletion. Interestingly, Bscl2 deletion reduced food intake and downregulated adipose beta3-adrenergic receptor (ADRB3) expression. Impaired ADRB3 signaling partially offsets upregulated browning induced energy expenditure and thermogenesis in Ad-mKO mice housed at ambient temperature. However, this counter-regulatory response was abrogated under thermoneutral conditions, resulting in even greater body mass loss in Ad-mKO mice. These findings suggest that Bscl2 regulates adipocyte lipolysis and beta adrenergic signaling to produce complex effects on adipose tissues and whole-body energy balance. PMID- 26269359 TI - Membrane-spanning lipids for an uncompromised monitoring of membrane fusion and intermembrane lipid transfer. AB - A Forster resonance energy transfer-based fusion and transfer assay was developed to study, in model membranes, protein-mediated membrane fusion and intermembrane lipid transfer of fluorescent sphingolipid analogs. For this assay, it became necessary to apply labeled reporter molecules that are resistant to spontaneous as well as protein-mediated intermembrane transfer. The novelty of this assay is the use of nonextractable fluorescent membrane-spanning bipolar lipids. Starting from the tetraether lipid caldarchaeol, we synthesized fluorescent analogs with fluorophores at both polar ends. In addition, we synthesized radioactive glycosylated caldarchaeols. These labeled lipids were shown to stretch through bilayer membranes rather than to loop within a single lipid layer of liposomes. More important, the membrane-spanning lipids (MSLs) in contrast to phosphoglycerides proved to be nonextractable by proteins. We could show that the GM2 activator protein (GM2AP) is promiscuous with respect to glycero- and sphingolipid transfer. Saposin (Sap) B also transferred sphingolipids albeit with kinetics different from GM2AP. In addition, we could unambiguously show that the recombinant activator protein Sap C x His6 induced membrane fusion rather than intermembrane lipid transfer. These findings showed that these novel MSLs, in contrast with fluorescent phosphoglycerolipids, are well suited for an uncompromised monitoring of membrane fusion and intermembrane lipid transfer. PMID- 26269361 TI - Combined oral contraceptives and risk of venous thromboembolism: there is higher risk in new generations compared to second generations, but paradoxically not in norgestimate-containing-pills. PMID- 26269362 TI - Paleolithic nutrition for metabolic syndrome: systematic review and meta analysis. AB - BACKGROUND: Paleolithic nutrition, which has attracted substantial public attention lately because of its putative health benefits, differs radically from dietary patterns currently recommended in guidelines, particularly in terms of its recommendation to exclude grains, dairy, and nutritional products of industry. OBJECTIVE: We evaluated whether a Paleolithic nutritional pattern improves risk factors for chronic disease more than do other dietary interventions. DESIGN: We conducted a systematic review of randomized controlled trials (RCTs) that compared the Paleolithic nutritional pattern with any other dietary pattern in participants with one or more of the 5 components of metabolic syndrome. Two reviewers independently extracted study data and assessed risk of bias. Outcome data were extracted from the first measurement time point (<=6 mo). A random-effects model was used to estimate the average intervention effect. The quality of the evidence was rated with the use of the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Four RCTs that involved 159 participants were included. The 4 control diets were based on distinct national nutrition guidelines but were broadly similar. Paleolithic nutrition resulted in greater short-term improvements than did the control diets (random effects model) for waist circumference (mean difference: -2.38 cm; 95% CI: -4.73, -0.04 cm), triglycerides (-0.40 mmol/L; 95% CI: -0.76, -0.04 mmol/L), systolic blood pressure (-3.64 mm Hg; 95% CI: -7.36, 0.08 mm Hg), diastolic blood pressure (-2.48 mm Hg; 95% CI: -4.98, 0.02 mm Hg), HDL cholesterol (0.12 mmol/L; 95% CI: 0.03, 0.28 mmol/L), and fasting blood sugar (-0.16 mmol/L; 95% CI: -0.44, 0.11 mmol/L). The quality of the evidence for each of the 5 metabolic components was moderate. The home-delivery (n = 1) and dietary recommendation (n = 3) RCTs showed similar effects with the exception of greater improvements in triglycerides relative to the control with the home delivery. None of the RCTs evaluated an improvement in quality of life. CONCLUSIONS: The Paleolithic diet resulted in greater short-term improvements in metabolic syndrome components than did guideline-based control diets. The available data warrant additional evaluations of the health benefits of Paleolithic nutrition. This systematic review was registered at PROSPERO (www.crd.york.ac.uk/PROSPERO) as CRD42014015119. PMID- 26269363 TI - Variation in hydration status within the normative range is associated with urinary biomarkers of systemic oxidative stress in Guatemalan preschool children. AB - BACKGROUND: Researchers have increasingly sought noninvasive methods to determine health and nutritional status in humans. Easy and painless to collect, human urine is a source of noninvasive biomarkers. OBJECTIVE: We aimed to explore the relation between systemic oxidative stress biomarkers excreted in urine and urinary osmolality (Uosm). DESIGN: The current trial was a descriptive, cross sectional study. We collected seventy-eight samples of 24-h urine in preschoolers who were attending daycare centers in the Western Highlands province of Quetzaltenango, Guatemala. After we measured the total urine volume (Uvol), the aliquot was stored for the later determination of Uosm as a hydration biomarker and to measure 15-isoprostane F2t (F2-Iso) and 8-hydroxydeoxyguanosine (8-OHdG) as biomarkers of cellular oxidation with the use of ELISA assay kits in Spain. Descriptive statistics and linear [Spearman rank-order (rs)] and nonlinear (goodness-of-fit) correlations were performed. RESULTS: Twenty-four hour Uvols ranged from 65 to 1670 mL, whereas the Uosm varied between 115 and 1102 mOsm/kg. With respect to oxidative biomarkers, the 24-h urinary output of F2-Iso and 8 OHdG had median values of 748 and 2793 ng/d, respectively. The Uvol correlated inversely and significantly with the concentrations of both oxidative biomarkers (F2-Iso rs = -0.603, P < 0.001; 8-OHdG rs = -0.433, P < 0.001), whereas the Uosm was correlated in a direct manner (F2-Iso rs = 0.541, P < 0.001; 8-OHdG rs = 0.782, P < 0.001) when analyzed as a concentration. Associations were weaker when they were analyzed as the total 24-h production. CONCLUSIONS: Preschool children from the Western Highlands of Guatemala show strong correlations between hydration status measured through the use of Uosm and biomarkers of oxidative stress in urine. Thus, a relatively superior hydration status is associated with a quantitative reduction in urinary excretion of systemic oxidation products. This trial was registered at clinicaltrials.gov as NCT02203890. PMID- 26269364 TI - Tea and flavonoid intake predict osteoporotic fracture risk in elderly Australian women: a prospective study. AB - BACKGROUND: Observational studies have linked tea drinking, a major source of dietary flavonoids, with higher bone density. However, there is a paucity of prospective studies examining the association of tea drinking and flavonoid intake with fracture risk. OBJECTIVE: The objective of this study was to examine the associations of black tea drinking and flavonoid intake with fracture risk in a prospective cohort of women aged >75 y. DESIGN: A total of 1188 women were assessed for habitual dietary intake with a food-frequency and beverage questionnaire. Incidence of osteoporotic fracture requiring hospitalization was determined through the Western Australian Hospital Morbidity Data system. Multivariable adjusted Cox regression was used to examine the HRs for incident fracture. RESULTS: Over 10 y of follow-up, osteoporotic fractures were identified in 288 (24.2%) women; 212 (17.8%) were identified as a major osteoporotic fracture, and of these, 129 (10.9%) were a hip fracture. In comparison with the lowest tea intake category (<=1 cup/wk), consumption of >=3 cups/d was associated with a 30% decrease in the risk of any osteoporotic fracture (HR: 0.70; 95% CI: 0.50, 0.96). Compared with women in the lowest tertile of total flavonoid intake (from tea and diet), women in the highest tertile had a lower risk of any osteoporotic fracture (HR: 0.65; 95% CI: 0.47, 0.88), major osteoporotic fracture (HR: 0.66; 95% CI: 0.45, 0.95), and hip fracture (HR: 0.58; 95% CI: 0.36, 0.95). For specific classes of flavonoids, statistically significant reductions in fracture risk were observed for higher intake of flavonols for any osteoporotic fracture and major osteoporotic fracture, as well as flavones for hip fracture (P < 0.05). CONCLUSION: Higher intake of black tea and particular classes of flavonoids were associated with lower risk of fracture-related hospitalizations in elderly women at high risk of fracture. PMID- 26269365 TI - Sugar-sweetened beverage consumption and incident hypertension: a systematic review and meta-analysis of prospective cohorts. AB - BACKGROUND: The role of sugar-sweetened beverages (SSBs) that contain free or bound fructose in the pathogenesis of hypertension remains unclear. OBJECTIVE: We conducted a systematic review and meta-analysis of prospective cohort studies to quantify the association between fructose-containing SSBs and risk of hypertension. DESIGN: MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane registry were searched from conception through 11 November 2014. Two independent reviewers extracted data and assessed the quality of studies (with the use of the Newcastle-Ottawa Scale). Risk estimates of extreme quantiles of SSB intake (lowest compared with highest) for hypertension incidence were generated with the use of generic inverse-variance methods with random-effects models and expressed as risk ratios with 95% CIs. Heterogeneity was assessed with the Cochran Q statistic and quantified with the I(2) statistic. RESULTS: Six prospective cohort studies (n = 240,508) with 79,251 cases of hypertension observed over >=3,197,528 person-years of follow-up were included. SSB consumption significantly increased the risk of developing hypertension by 12% (risk ratio: 1.12; 95% CI: 1.06, 1.17) with evidence of significant heterogeneity (I(2) = 62%, P = 0.02) when highest [>=1 serving (6.7, 8, or 12 oz)/d] and lowest (none) quantiles of intake were compared. With the use of a dose-response analysis, a significant 8.2% increase in risk of every additional SSB per day from none to >=1 SSB/d (beta = 0.0027, P < 0.001) was identified. Limitations include unexplained heterogeneity and residual confounding. The results may also have been subject to collinearity effects from aspects of a Western dietary pattern. CONCLUSIONS: SSBs were associated with a modest risk of developing hypertension in 6 cohorts. There is a need for high quality randomized trials to assess the role of SSBs in the development of hypertension and its complications. This study was registered at clinicaltrials.gov as NCT01608620. PMID- 26269366 TI - Dietary fiber intake and risk of colorectal cancer and incident and recurrent adenoma in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. AB - BACKGROUND: Dietary fiber has been associated with a reduced risk of colorectal cancer. However, it remains unclear at which stage in the carcinogenic pathway fiber may act or which food sources of dietary fiber may be most beneficial against colorectal cancer development. OBJECTIVE: The objective was to prospectively evaluate the association between dietary fiber intake and the risk of incident and recurrent colorectal adenoma and incident colorectal cancer. DESIGN: Study participants were identified from the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Participants received flexible sigmoidoscopy at baseline and 3 or 5 y after. Dietary fiber intake was measured by using a self-reported dietary questionnaire. The colorectal cancer, incident adenoma, and recurrent adenoma analyses were based on 57,774, 16,980, and 1667 participants, respectively. Unconditional logistic regression was used to assess the risk of incident and recurrent adenoma, and Cox proportional hazards models were used to assess the risk of colorectal cancer across categories of dietary fiber intake, with adjustment for potential confounders. RESULTS: Elevated total dietary fiber intake was associated with a significantly reduced risk of incident distal colorectal adenoma (ORhighest vs. lowest tertile of intake: 0.76; 95% CI: 0.63, 0.91; P-trend = 0.003) but not recurrent adenoma (P-trend = 0.67). Although the association was not statistically significant for colorectal cancer overall (HR: 0.85; 95% CI: 0.70, 1.03; P-trend = 0.10), a reduced risk of distal colon cancer was observed with increased total fiber intake (HR: 0.62; 95% CI: 0.41, 0.94; P-trend = 0.03). Protective associations were most notable for fiber originating from cereals or fruit. CONCLUSIONS: This large, prospective study within a population-based screening trial suggests that individuals consuming the highest intakes of dietary fiber have reduced risks of incident colorectal adenoma and distal colon cancer and that this effect of dietary fiber, particularly from cereals and fruit, may begin early in colorectal carcinogenesis. This trial was registered at clinicaltrials.gov as NCT01696981. PMID- 26269367 TI - High concentrations of folate and unmetabolized folic acid in a cohort of pregnant Canadian women and umbilical cord blood. AB - BACKGROUND: Mandatory fortification, prevalent supplement use, and public health guidelines recommending periconceptional supplementation have increased folic acid intakes in North American pregnant women. However, the effects of increased folic acid intakes during pregnancy on maternal and cord blood folate concentrations have not been well established. OBJECTIVES: In this prospective study, we determined maternal and cord blood concentrations of folate and unmetabolized folic acid (UMFA) in a cohort of pregnant Canadian women and their newborns and examined the effect of maternal intakes of folate and folic acid and fetal genetic variants in folate metabolism on folate status. DESIGN: Folate and folic acid intakes of 368 Canadian pregnant women were assessed in early (0-16 wk) and late (23-37 wk) pregnancy. Blood concentrations of folate and UMFA were measured with the use of immunoassays and liquid chromatography-mass spectrometry, respectively, in maternal samples in early pregnancy (12-16 wk), at delivery (28-42 wk), and in cord blood. Four fetal genetic variants of the 5,10 methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase (DHFR) genes were assessed for their association with cord blood concentrations of folate and UMFA. RESULTS: Geometric mean (95% CI) maternal red blood cell (RBC) folate concentrations were 2417 nmol/L (2362, 2472 nmol/L ) and 2793 nmol/L (2721, 2867 nmol/L ) in early pregnancy and at delivery, respectively. The mean (95% CI) cord RBC folate concentration was 2689 nmol/L (2614, 2765 nmol/L). UMFA was detectable in >90% of maternal and cord plasma samples. Although 3 fetal MTHFR and DHFR genetic variants had no effect, the fetal MTHFR 677TT genotype was associated with significantly lower cord serum (P = 0.03) and higher cord RBC (P = 0.02) folate concentrations than those of the wild type. CONCLUSIONS: Notwithstanding differences in assays, maternal and cord RBC folate and plasma UMFA concentrations were higher than previously reported values. Functional ramifications of high folate and UMFA concentrations in maternal and fetal circulation warrant additional investigation because an excess folate status may affect long-term health outcomes of the offspring. This study was registered at www.clinicaltrials.gov as NCT02244684. PMID- 26269368 TI - Body composition of children with cancer during treatment and in survivorship. AB - BACKGROUND: Malnutrition as assessed with the use of body-composition measurements is a poorly understood short- and long-term complication of childhood cancer. OBJECTIVES: We aimed to evaluate the body composition of 2 childhood cancer cohorts as follows: 1) children currently undergoing cancer treatment and 2) childhood cancer survivors. We also aimed to compare the prevalence of obesity and undernutrition between the cancer groups and investigate the impact of cancer type on body composition. DESIGN: Eighty-two children during the treatment of cancer and 53 childhood cancer survivors were involved in the study. Height, weight, body cell mass, percentage of fat, fat mass index, and fat-free mass index were assessed. Subjects were compared with age- and sex-matched healthy controls. RESULTS: The on-treatment group had a higher percentage of fat (P = 0.0001) and fat mass index (P = 0.0001) and a significantly lower body cell mass index (P = 0.0001) and fat-free mass index (P = 0.003) than did matched controls. The survivor group had a significantly higher percentage of fat (P = 0.03) and fat mass index (P = 0.04) and significantly lower body cell mass index (P = 0.0001) than did matched controls. The prevalence of undernutrition was high in both groups with 48% (95% CI: 36%, 60%) of the on treatment group and 53% (95% CI: 40%, 66%) of the survivors considered undernourished. According to the percentage of fat cutoffs, significantly more on treatment patients were obese (55%; 95% CI: 40%, 60%) than were survivors (26%; 95% CI: 14%, 38%) (P = 0.005). There were no statistically significant differences in body composition between cancer types in either the on-treatment or the survivor group. CONCLUSIONS: Overnutrition and undernutrition are major concerns in the short and long term for children with cancer. Children treated for cancer have increased fat mass and decreased body cell mass, which are evident during treatment and in survivorship. This trial was registered at http://www.ANZCTR.org.au as ACTRN12614001279617 and ACTRN12614001269628. PMID- 26269370 TI - Breaking the feast. PMID- 26269369 TI - Polyphenol metabolome in human urine and its association with intake of polyphenol-rich foods across European countries. AB - BACKGROUND: An improved understanding of the contribution of the diet to health and disease risks requires accurate assessments of dietary exposure in nutritional epidemiologic studies. The use of dietary biomarkers may improve the accuracy of estimates. OBJECTIVE: We applied a metabolomic approach in a large cohort study to identify novel biomarkers of intake for a selection of polyphenol containing foods. The large chemical diversity of polyphenols and their wide distribution over many foods make them ideal biomarker candidates for such foods. DESIGN: Metabolic profiles were measured with the use of high-resolution mass spectrometry in 24-h urine samples from 481 subjects from the large European Prospective Investigation on Cancer and Nutrition cohort. Peak intensities were correlated to acute and habitual dietary intakes of 6 polyphenol-rich foods (coffee, tea, red wine, citrus fruit, apples and pears, and chocolate products) measured with the use of 24-h dietary recalls and food-frequency questionnaires, respectively. RESULTS: Correlation (r > 0.3, P < 0.01 after correction for multiple testing) and discriminant [pcorr (1) > 0.3, VIP > 1.5] analyses showed that >2000 mass spectral features from urine metabolic profiles were significantly associated with the consumption of the 6 selected foods. More than 80 polyphenol metabolites associated with the consumption of the selected foods could be identified, and large differences in their concentrations reflecting individual food intakes were observed within and between 4 European countries. Receiver operating characteristic curves showed that 5 polyphenol metabolites, which are characteristic of 5 of the 6 selected foods, had a high predicting ability of food intake. CONCLUSION: Highly diverse food-derived metabolites (the so-called food metabolome) can be characterized in human biospecimens through this powerful metabolomic approach and screened to identify novel biomarkers for dietary exposures, which are ultimately essential to better understand the role of the diet in the cause of chronic diseases. PMID- 26269372 TI - Benefit of vitamin B-12 supplementation in asymptomatic elderly: a matter of endpoints. PMID- 26269371 TI - Effects of a behavioral intervention that emphasizes spices and herbs on adherence to recommended sodium intake: results of the SPICE randomized clinical trial. AB - BACKGROUND: For decades, dietary sodium intake in the United States has remained high, and few studies have examined strategies for maintaining recommended intakes. OBJECTIVE: We examined the effects of a behavioral intervention, which emphasized spices and herbs, on the maintenance of sodium intake at the recommended intake of 1500 mg/d in individuals to whom the US Dietary Guidelines for Americans apply. DESIGN: We conducted a 2-phase study that included adults >=18 y of age for whom Dietary Guidelines for Americans recommends 1500 mg Na/d. The study was conducted in Baltimore, Maryland, from 2012 to 2014. In phase 1, 55 individuals consumed a low-sodium diet for 4 wk. Participants were provided all foods, snacks, and calorie-containing drinks. In phase 2, 40 participants from phase 1 were randomly assigned to either a behavioral intervention to reduce sodium intake (n = 20) or a self-directed control group (n = 20) for 20 wk. The primary study outcome was the change in mean 24-h urinary sodium excretion during phase 2. Linear regression analyses were used to determine intervention effects on urinary sodium excretion. RESULTS: Participant characteristics were as follows: women: 65%; African American: 88%; hypertension: 63%; diabetes: 18%; mean age: 61 y; and mean body mass index (in kg/m(2)): 30. At the end of phase 2, mean 24-h sodium excretion was lower in the behavioral intervention than in the self-directed group (mean difference: -956.8 mg/d; 95% CI: -1538.7, -374.9 mg/d) after sodium intake at screening was controlled for (P = 0.002). These findings persisted in sensitivity analyses that excluded potentially incomplete urine collections [Mage's equation mean difference: -1090 mg/d (P = 0.001); Joosens' equation mean difference: -796 mg/d (P = 0.04)]. CONCLUSIONS: A multifactorial behavioral intervention emphasizing spices and herbs significantly reduced sodium intake. Because of the ubiquity of sodium in the US food supply, multilevel strategies addressing individual behaviors and the food supply are needed to improve adherence to recommendations. This trial was registered at clinicaltrials.gov as NCT01615159. PMID- 26269373 TI - Whole-grain and blood lipid changes in apparently healthy adults: a systematic review and meta-analysis of randomized controlled studies. AB - BACKGROUND: Whole grains are recognized for their potential role in preventing cardiovascular diseases; however, results from randomized controlled studies on blood lipids are inconsistent, potentially because of compositional differences between individual grain types for some nutrients, including dietary fiber. OBJECTIVE: Using a meta-analytic approach, we assessed the effect of whole-grain compared with non-whole-grain foods on changes in total cholesterol (TC), LDL cholesterol, HDL cholesterol, and triglycerides. DESIGN: We conducted a systematic literature search in selected databases. Studies were included if they were randomized controlled comparisons between whole-grain foods and a non-whole grain control in adults. A total of 6069 articles were screened for eligibility, and data were extracted from 24 studies. Weighted mean differences were calculated, and meta-regression analyses were performed for whole-grain dose, study duration, and baseline TC concentration. RESULTS: Overall, whole-grain intake lowered LDL cholesterol (weighted difference: -0.09 mmol/L; 95% CI: -0.15, -0.03 mmol/L; P < 0.01) and TC (weighted difference: -0.12 mmol/L; 95% CI: -0.19, -0.05 mmol/L; P < 0.001) compared with the control. Whole-grain oat had the greatest effect on TC (weighted difference: -0.17 mmol/L; 95% CI: -0.10, -0.25 mmol/L; P < 0.001). No effect of whole-grain foods on HDL cholesterol was seen, whereas whole-grain foods tended to lower triglycerides compared with the control (weighted difference: -0.04 mmol/L; 95% CI: -0.08, 0.01; P = 0.10). No association was found between whole-grain dose or baseline TC concentration and any of the outcomes, whereas study duration was positively associated with changes in TC and LDL cholesterol. CONCLUSIONS: Consumption of whole-grain diets lowers LDL cholesterol and TC, but not HDL cholesterol or triglycerides, compared with consumption of non-whole-grain control diets. Whole-grain oat appears to be the most effective whole grain for lowering cholesterol. PMID- 26269375 TI - Aortic Dehiscence During Endovascular Sealing for Ruptured Abdominal Aortic Aneurysms. AB - PURPOSE: To present a case of aneurysm disruption during endovascular sealing of a ruptured abdominal aortic aneurysm. CASE REPORT: A 91-year-old woman presented with a ruptured abdominal aortic aneurysm. Her aneurysm morphology was unsuitable for standard or fenestrated endovascular repair, whereas open repair was considered to have an increased perioperative risk owing to multiple comorbidities. The Nellix endovascular sealing system was used. The balloon expandable stent-grafts were deployed, but in the presence of aneurysm rupture, it was decided not to prefill the endobags with saline. The patient developed hypotension during endobag filling, which resolved once target pressure was reached. The procedure was completed uneventfully, and the completion angiogram revealed no endoleak. The time from guidewire insertion to completion angiogram was 24 minutes. Over the following days, she developed a gradual drop in hemoglobin, and computed tomographic angiography revealed an increased retroperitoneal hematoma and pronounced disruption of the calcified rim of the aortic sac compared to the preoperative imaging. She was managed with supportive treatment, demonstrating remarkable progress. She remains in good health 4 months later. CONCLUSION: Endovascular sealing can be used in patients with ruptured abdominal aortic aneurysm. Intraoperative endobag saline prefill should be avoided to minimize the risk of aortic wall disruption. PMID- 26269374 TI - Bevacizumab treatment of macular edema in CRVO and BRVO: long-term follow-up. (BERVOLT study: Bevacizumab for RVO long-term follow-up). AB - PURPOSE: To assess the efficacy and safety of intraocular injections of bevacizumab in patients with macular edema (ME) following branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO). METHODS: Retrospective, non-comparative case series. Patients >=18 years of age with ME secondary to BRVO or CRVO who received a minimum of one intravitreal injection of bevacizumab with a follow-up >3 months were included. Primary endpoints were mean change in best corrected visual acuity (BCVA) from baseline to 12 and 24 months, and mean change in central macular thickness (CMT) after 3 injections. Secondary endpoints were mean change in BCVA and CMT from baseline to end of follow-up, number of injections, and ocular adverse events. RESULTS: Eighty-seven eyes with BRVO and 65 eyes with CRVO were included. Mean follow-up time was 24.4 and 26.1 months in the BRVO and CRVO groups, respectively. The mean change in BCVA was 0.25 LogMAR in the BRVO group and -0.118 LogMAR in the CRVO group. CONCLUSION: Visual acuity outcomes in the CRVO group were poorer, especially in patients with low baseline BCVA. PMID- 26269376 TI - Australian survey on current practices for breast radiotherapy. AB - INTRODUCTION: Detailed, published surveys specific to Australian breast radiotherapy practice were last conducted in 2002. More recent international surveys specific to breast radiotherapy practice include a European survey conducted in 2008/2009 and a Spanish survey conducted in 2009. Radiotherapy techniques continue to evolve, and the utilisation of new techniques, such as intensity-modulated radiation therapy (IMRT), is increasing. This survey aimed to determine current breast radiotherapy practices across Australia. METHOD: An online survey was completed by 50 of the 69 Australian radiation therapy treatment centres. RESULTS: Supine tangential beam whole breast irradiation remains the standard of care for breast radiotherapy in Australia. A growing number of institutions are exploring prone positioning and IMRT utilisation. This survey demonstrated a wide variation in the benchmarks used to limit and report organ at risk doses, prescribed dose regimen, and post-mastectomy bolus practices. This survey also indicated, when compared with international literature, that there may be less interest in or uptake of external beam partial breast irradiation, prone positioning, simultaneous integrated boost and breath hold techniques. These are areas where further review and research may be warranted to ensure Australian patients are receiving the best care possible based on the best evidence available. CONCLUSION: This survey provides insight into the current radiotherapy practice for breast cancer in Australia. PMID- 26269377 TI - Obesity Phytotherapy: Review of Native Herbs Used in Traditional Medicine for Obesity. AB - Obesity is an important disorders due to which 25 million deaths occur annually worldwide. Synthetic drugs for weight loss have low efficacy and high side effects. Apart from synthetic drugs in modern medicine, various other methods including the use of herbal medications are used to induce weight loss. Cambodia hoodia, green tea, Citrus aurantium, white beans, fenugreek, caffeine, ephedrine, capsaicin, yohimbine, chitosan, fitostreols, and guar gum have been studied in clinical trials and their effects have been confirmed. It seems necessary to study more to determine the effectiveness and safety of medicinal plants and herbal extracts as well as pharmaceutically active ingredients that may have the property of weight loss. In this article, we aimed to review recent knowledge about medicinal plants that are recommended for weight loss. PMID- 26269378 TI - GbEXPATR, a species-specific expansin, enhances cotton fibre elongation through cell wall restructuring. AB - Cotton provides us the most important natural fibre. High fibre quality is the major goal of cotton breeding, and introducing genes conferring longer, finer and stronger fibre from Gossypium barbadense to Gossypium hirsutum is an important breeding strategy. We previously analysed the G. barbadense fibre development mechanism by gene expression profiling and found two homoeologous fibre-specific alpha-expansins from G. barbadense, GbEXPA2 and GbEXPATR. GbEXPA2 (from the DT genome) is a classical alpha-expansin, while its homoeolog, GbEXPATR (AT genome), encodes a truncated protein lacking the normal C-terminal polysaccharide-binding domain of other alpha-expansins and is specifically expressed in G. barbadense. Silencing EXPA in G. hirsutum induced shorter fibres with thicker cell walls. GbEXPA2 overexpression in G. hirsutum had no effect on mature fibre length, but produced fibres with a slightly thicker wall and increased crystalline cellulose content. Interestingly, GbEXPATR overexpression resulted in longer, finer and stronger fibres coupled with significantly thinner cell walls. The longer and thinner fibre was associated with lower expression of a number of secondary wall associated genes, especially chitinase-like genes, and walls with lower cellulose levels but higher noncellulosic polysaccharides which advocated that a delay in the transition to secondary wall synthesis might be responsible for better fibre. In conclusion, we propose that alpha-expansins play a critical role in fibre development by loosening the cell wall; furthermore, a truncated form, GbEXPATR, has a more dramatic effect through reorganizing secondary wall synthesis and metabolism and should be a candidate gene for developing G. hirsutum cultivars with superior fibre quality. PMID- 26269379 TI - Mammalophilic feeding behaviour of Culex quinquefasciatus mosquitoes collected in the cities of Chetumal and Cancun, Yucatan Peninsula, Mexico. AB - OBJECTIVE: The studie describes the blood-feeding behaviour of mosquitoes in Mexico, to understand host-vector relationships and dynamics of disease transmission. METHODS: From September 2012 to November 2012 and in November 2013, 911 blood-fed Cx. quinquefasciatus mosquitoes were collected with aspirators inside houses in Chetumal and Cancun. Blood meals were analysed by PCR and subsequent Sanger sequencing of the cytochrome b gene. RESULTS: 93.3% of mosquitoes fed on mammals, 6.5% on birds and 0.2% on reptiles. The most frequent vertebrate hosts were humans (65.4%), dogs (23.2%), chicken (5.4%), cattle (2.2%) and cats (1.8%). CONCLUSIONS: Cx. quinquefasciatus most frequently fed on humans and dogs in both studied cities, which is in contrast to a previous study that demonstrated lower prevalence of mammalian blood in engorged Cx. quinquefasciatus. PMID- 26269380 TI - The IS1111 insertion sequence used for detection of Coxiella burnetii is widespread in Coxiella-like endosymbionts of ticks. AB - Coxiella is a genus of obligate intracellular bacteria engaged in a variety of interactions with eukaryotes. The type species, Coxiella burnetii, infects several vertebrate species, including humans, and is the causative agent of Q fever. Multiple copies of a specific transposable element, the insertion sequence IS1111, are present in the genome of C. burnetii and are routinely used for confirmation of Q fever cases. Recently, many Coxiella-like bacteria that are closely related but genetically distinct to C. burnetii have been found in ticks. These Coxiella-like bacteria are maternally inherited endosymbionts, present at high prevalence in tick populations and engaged in mutualistic interactions with their arthropod hosts. In this study, the presence of IS1111 was examined in the Coxiella-like endosymbionts and in bacteria of the Coxiella sister-genus, Rickettsiella. This screening reveals that a wide range of IS1111 copies were present in the Coxiella-like endosymbionts of ticks. DNA sequencing further identified genetically divergent IS1111 copies, including degraded copies that constitute an important genomic fossil record of past IS1111 expansions. These results show that IS1111 is not specific to C. burnetii, suggesting that Q fever detection assays based only on this element may lead to misidentification with Coxiella-like endosymbionts. PMID- 26269381 TI - A comparative analysis of distribution and conservation of microsatellites in the transcripts of sequenced Fusarium species and development of genic-SSR markers for polymorphism analysis. AB - We used an in silico approach to survey and compare microsatellites in transcript sequences of four sequenced members of genus Fusarium. G + C content of transcripts was found to be positively correlated with the frequency of SSRs. Our analysis revealed that, in all the four transcript sequences studied, the occurrence, relative abundance and density of microsatellites varied and was not influenced by transcript sizes. No correlation between relative abundance and transcript sizes was observed. The relative abundance and density of microsatellites were highest in the transcripts of Fusarium solani when compared with F. graminearum, F. verticillioides and F. oxysporum. The maximum frequency of SSRs among all four sequence sets was of trinucleotide repeats (67.8%), whereas the dinucleotide repeat represents <1%. Among all classes of repeats, 36.5% motifs were found conserved within Fusarium species. In order to study polymorphism within Fusarium isolates, 11 polymorphic genic-SSR markers were developed. Of the 11 markers, 5 were from F. oxysporum and remaining 6 belongs to F. solani. SSR markers from F. oxysporum were found to be more polymorphic (38%) as compared to F. solani (26%). Eleven polymorphic markers obtained in this study clearly demonstrate the utility of newly developed SSR markers in establishing genetic relationships among different isolates of Fusarium. PMID- 26269383 TI - Comparison of complications associated with peripherally inserted central catheters and HickmanTM catheters in patients with intestinal failure receiving home parenteral nutrition. Six-year follow up study. AB - BACKGROUND & AIM: Patients with intestinal failure (IF) are dependent on parenteral nutrition delivered through central access such as HickmanTM catheters. The peripherally inserted central catheter (PICC) is becoming increasingly popular for the purpose. The aim of the present study was to compare complication rates between the two types of catheters. PATIENTS AND METHODS: Over a six-year period (2008-2014), we included 136 patients with IF receiving home parenteral nutrition (HPN). These patients had a total of 295 catheters (169 HickmanTM catheters and 126 PICCs). Data were collected by reviewing their medical records. Incidences are given per 1000 catheter days. Data are given as means +/- standard deviation (SD) and compared using independent student's t tests, Mann-Whitney-Wilcoxon, and X(2)-tests. A survival analysis for time to the first infection was conducted using Cox regression. RESULTS: The total number of catheter days was 54,912 days for HickmanTM catheters (mean dwell time 325 +/- 402) and 15,974 days for PICCs (mean dwell time 127 +/- 121), respectively. The incidence of catheter-related blood stream infection (CRBSI) per 1000 catheter days was significantly lower for HickmanTM catheters compared to PICCs (0.56 vs. 1.63, p < 0.05). The mean time to first CRBSI was significantly shorter for PICCs compared to HickmanTM catheters (84 +/- 94 days vs. 297 +/- 387 days, p < 0.05), which was confirmed with a cox analysis corrected for age and gender. A total of 75 catheters were removed due to CRBSI, 49 HickmanTM catheters and 26 PICCs respectively. In addition, PICCs were more often removed due to local infection/phlebitis and mechanical causes (p < 0.001). CONCLUSION: We found a higher risk and shorter time to first CRBSI in PICCs compared to Hickman catheters supporting that PICCs should mainly be chosen for planned HPN up to 3-6 months. We therefore conclude that the choice of catheter must still be determined on an individual basis. PMID- 26269384 TI - Proteome and metabolome profiling of wild-type and YCA1-knock-out yeast cells during acetic acid-induced programmed cell death. AB - Caspase proteases are responsible for the regulated disassembly of the cell into apoptotic bodies during mammalian apoptosis. Structural homologues of the caspase family (called metacaspases) are involved in programmed cell death in single-cell eukaryotes, yet the molecular mechanisms that contribute to death are currently undefined. Recent evidence revealed that a programmed cell death process is induced by acetic acid (AA-PCD) in Saccharomyces cerevisiae both in the presence and absence of metacaspase encoding gene YCA1. Here, we report an unexpected role for the yeast metacaspase in protein quality and metabolite control. By using an "omics" approach, we focused our attention on proteins and metabolites differentially modulated en route to AA-PCD either in wild type or YCA1-lacking cells. Quantitative proteomic and metabolomic analyses of wild type and Deltayca1 cells identified significant alterations in carbohydrate catabolism, lipid metabolism, proteolysis and stress-response, highlighting the main roles of metacaspase in AA-PCD. Finally, deletion of YCA1 led to AA-PCD pathway through the activation of ceramides, whereas in the presence of the gene yeast cells underwent an AA-PCD pathway characterized by the shift of the main glycolytic pathway to the pentose phosphate pathway and a proteolytic mechanism to cope with oxidative stress. SIGNIFICANCE: The yeast metacaspase regulates both proteolytic activities through the ubiquitin-proteasome system and ceramide metabolism as revealed by proteome and metabolome profiling of YCA1-knock-out cells during acetic-acid induced programmed cell death. PMID- 26269385 TI - Lipopeptide Nanoparticles: Development of Vaccines against Hookworm Parasite. AB - Necator americanus (hookworm) infects over half a billion people worldwide. Anthelminthic drugs are commonly used to treat the infection; however, vaccination is a more favorable strategy to combat this parasite. We designed new B-cell peptide epitopes based on the aspartic protease of N. americanus (Na-APR 1). The peptides were conjugated to self-adjuvanting lipid core peptide (LCP) systems via stepwise solid-phase peptide synthesis (SPPS) and copper catalyst azide-alkyne cycloaddition (CuAAC) reactions. The LCP vaccine candidates were able to self-assemble into nanoparticles, were administered to mice without the use of additional adjuvant, and generated antibodies that recognized the parent epitope. However, only one LCP derivative was able to produce a high titer of antibodies specific to Na-APR-1; circular dichroism analyses of this compound showed a beta-sheet conformation for the incorporated epitope. This study provides important insight in epitope and delivery system design for the development of a vaccine against hookworm infections. PMID- 26269387 TI - Association between a color and a manual response activation modulates the response planning of typically developing children in a subsequent Simon task. AB - The Simon effect usually refers to the observation that responding to a nonspatial feature of a stimulus is faster when the position of the stimulus (task-irrelevant) matches the position of the to-be-executed response. The Simon effect can disappear when the Simon task is preceded by a spatial compatibility task with an incompatible mapping. In this experiment, during a preliminary phase, 20 children had to decide whether the outline of a colored stimulus was dotted or continuous. Green stimuli were presented exclusively on the right, whereas red stimuli were presented on the left (the color was task-irrelevant). The participants then had to perform a Simon task. When the instructions required them to press either the left or the right button for red or green stimuli, respectively (Group A), the Simon effect on response latencies was not significant. With the opposite instructions (the right or left button for red or green stimuli, respectively; Group B), the Simon effect was significant on response latencies. The Simon effect was significant on movement times for both groups. These results suggest that during the preliminary phase, each color became associated with the manual response automatically activated by that color's position. In the subsequent Simon task, the presentation of the color activated the associated response. This modulated the planning of the to-be executed response. PMID- 26269386 TI - Spatiotemporal Form Integration: sequentially presented inducers can lead to representations of stationary and rigidly rotating objects. AB - Objects in the world often are occluded and in motion. The visible fragments of such objects are revealed at different times and locations in space. To form coherent representations of the surfaces of these objects, the visual system must integrate local form information over space and time. We introduce a new illusion in which a rigidly rotating square is perceived on the basis of sequentially presented Pacman inducers. The illusion highlights two fundamental processes that allow us to perceive objects whose form features are revealed over time: Spatiotemporal Form Integration (STFI) and Position Updating. STFI refers to the spatial integration of persistent representations of local form features across time. Position updating of these persistent form representations allows them to be integrated into a rigid global motion percept. We describe three psychophysical experiments designed to identify spatial and temporal constraints that underlie these two processes and a fourth experiment that extends these findings to more ecologically valid stimuli. Our results indicate that although STFI can occur across relatively long delays between successive inducers (i.e., greater than 500 ms), position updating is limited to a more restricted temporal window (i.e., ~300 ms or less), and to a confined range of spatial (mis)alignment. These findings lend insight into the limits of mechanisms underlying the visual system's capacity to integrate transient, piecemeal form information, and support coherent object representations in the ever-changing environment. PMID- 26269388 TI - In vivo expression of antimicrobial peptides in atopic dermatitis. AB - The aim of this review is to present findings on expression of antimicrobial peptides (AMPs) in atopic dermatitis (AD) skin, focusing only on in vivo studies, and to discuss differences in results obtained using various skin sampling techniques and different methodology for analysis of AMPs. The review also includes a discussion of the effect of frequently used treatments on AMP expression. Many studies have shown a reduced level of AMPs in lesional AD skin when compared to psoriatic skin, explaining the high frequency of AD-related infections. Interestingly, however, non-lesional AD skin has shown the same upregulation of AMPs after barrier disruption as non-lesional psoriatic skin. Various methods have been used to analyse AMP expression in the skin, and when comparing these methods, differences are revealed in AMP expression depending on the method used for sampling and analysis. Comparisons indicate that analyses of mRNA levels of AMPs may find greater differences in expression than analyses of protein levels. Few studies evaluate the effect of topical treatments on the expression of AMPs, and these indicate an inhibition of AMP expression, particularly after use of corticosteroids. AMPs are important components of the skin as a defense against infections, and despite much research, the clinical importance of the effect of common treatments, including systemic treatments for AD and the interplay between AMPs and the skin microbiome, is still largely unknown. PMID- 26269389 TI - Facial multinucleate cell angiohistiocytoma: long-term remission with 585 nm pulsed dye laser. PMID- 26269390 TI - Repair of a large pharyngocutaneous fistula with a free jejunal patch flap after salvage laryngectomy: A case report. AB - Preoperative chemoradiation therapy increases the risk of pharyngocutaneous fistula (PCF) after laryngectomy. In this report, we describe the use of a free jejunal patch flap and a deltopectoral flap for surgical treatment of a large PCF. A 52-year-old man underwent salvage laryngectomy and right neck dissection after concurrent radiotherapy for laryngeal carcinoma. On postoperative day 5, a pharyngeal fistula and neck abscess occurred with the right internal jugular vein thrombosis. We sutured the pharyngeal mucosa to the cervical skin to avoid carotid artery exposure, and we also ligated the right internal jugular vein. The PCF developed afterwards. The patient was being fed through a nasogastric tube and the fistula had increased in size. At the time of surgery, the external orifice became 5 cm * 5 cm in size. We performed the repair with a free jejunal patch flap and a deltopectoral flap. The harvested jejunum was opened along its antimesenteric border to design a sufficient free jejunal flap to cover the large PCF. A deltopectoral pedicled flap was used to reconstruct the neck skin defect to resurface the free jejunal patch flap. Both flaps survived. The patient could resume an oral diet 2 weeks after surgery. At 1 month after surgery, the skin pedicle of the deltopectoral flap was divided. There was no contracture or stricture 3 years after surgery and he maintained a regular diet. Reconstruction with a free jejunal patch flap and a deltopectoral flap may be a suitable method for repair of a large PCF. (c) 2014 Wiley Periodicals, Inc. Microsurgery 37:61 65, 2017. PMID- 26269391 TI - Implantation of everolimus-eluting bioresorbable scaffolds in a diabetic all comers population. AB - BACKGROUND: Diabetes is associated with aggressive atherosclerosis, leading to an increased risk of in-stent restenosis and stent thrombosis. Bioresorbable scaffolds (BRS) are a new technology for the treatment of coronary lesions that might be beneficial due to their dissolving character, especially in diabetic patients. OBJECTIVE: This study was designed to evaluate feasibility and mid-term clinical outcome of the implantation of PLLA-based, everolimus-eluting BRS for the treatment of coronary lesions in a diabetic all-comers population. METHODS: All patients of an all-comers registry with diabetes eligible for BRS implantation were included. Outcome parameters were target vessel failure (TVF), major adverse cardiac events (MACE) including target lesion revascularization (TLR), cardiac death, and myocardial infarction. Follow-up was conducted via telephone and/or office visit. RESULTS: A total of 120 diabetic patients were included. Of all diabetics, 35.0% had insulin-dependent diabetes, and all other patients were treated with oral antidiabetics or dietary modification. The median age was 67 (59-72) years and 26.7% were female. Patients underwent coronary angiography due to acute coronary syndrome in 50.8%. Of 127 lesions, 60.6% were B2/C lesions according to ACC/AHA classification. The 6-month rates of TVF, TLR, and MACE were 8.9, 2.7, and 8.4%, respectively. CONCLUSION: This evaluation confirms reasonable clinical outcome of bioresorbable vascular scaffold implantation in a high-risk diabetic population with predominately complex lesions during daily clinical practice. Nevertheless, long-term data are required for final evaluation. PMID- 26269392 TI - Job dissatisfaction and burnout of nurses in Hunan, China: A cross-sectional survey. AB - In this study, we focused on measuring levels of nurse burnout and job dissatisfaction in the daily practice of nurses in Hunan province, China, analyzed factors related to nurse burnout and job dissatisfaction, and explored the relationship between them. Previous studies have shown a high level of burnout and job dissatisfaction among nurses worldwide. A cross-sectional survey of 1100 nurses was conducted. The nurses worked at 20 hospitals in 11 cities and counties throughout China's Hunan province. Nurse burnout was measured by the Maslach Burnout Inventory. Nurse-rated job dissatisfaction was described using a four point scale, and work environment was measured using the Nursing Work Index Practice Environment Scale. The results showed that nurses had high burnout scores and were dissatisfied with their jobs. Staffing, work environment, and work hours were all significantly associated with nurse burnout and job dissatisfaction. Adequate staffing, improved work environment, and reasonable work hours are related to decreasing nurse burnout and job dissatisfaction. PMID- 26269393 TI - What Is the Addiction World Like? Understanding the Lived Experience of the Individuals' Illicit Drug Addiction in Taiwan. AB - PURPOSE: This study focuses on the participants' lived experience of addiction. DESIGN AND METHODS: The study presents a qualitative method. The use of the fieldwork-based participant observation and in-depth interviews guided the data collection and analysis. FINDINGS: Three major themes of addiction emerge from the analysis: incorrigible conduct, inexcusable compromise, and inevitable corruption. PRACTICE IMPLICATIONS: This study provides a better understanding of what the world is like for people struggling with addiction and also enhances the healthcare professionals' knowledge of the individual's experience of addiction. This knowledge is essential for clinicians to understand this experience as a framework for planning and implementing appropriate treatment. PMID- 26269394 TI - Visualizing nanoscale excitonic relaxation properties of disordered edges and grain boundaries in monolayer molybdenum disulfide. AB - Two-dimensional monolayer transition metal dichalcogenide semiconductors are ideal building blocks for atomically thin, flexible optoelectronic and catalytic devices. Although challenging for two-dimensional systems, sub-diffraction optical microscopy provides a nanoscale material understanding that is vital for optimizing their optoelectronic properties. Here we use the 'Campanile' nano optical probe to spectroscopically image exciton recombination within monolayer MoS2 with sub-wavelength resolution (60 nm), at the length scale relevant to many critical optoelectronic processes. Synthetic monolayer MoS2 is found to be composed of two distinct optoelectronic regions: an interior, locally ordered but mesoscopically heterogeneous two-dimensional quantum well and an unexpected ~300 nm wide, energetically disordered edge region. Further, grain boundaries are imaged with sufficient resolution to quantify local exciton-quenching phenomena, and complimentary nano-Auger microscopy reveals that the optically defective grain boundary and edge regions are sulfur deficient. The nanoscale structure property relationships established here are critical for the interpretation of edge- and boundary-related phenomena and the development of next-generation two dimensional optoelectronic devices. PMID- 26269395 TI - Risk and protective factors in gifted children with dyslexia. AB - This study investigated risk and protective factors associated with dyslexia and literacy development, both at the group and individual level, to gain more insight in underlying cognitive profiles and possibilities for compensation in high-IQ children. A sample of 73 Dutch primary school children included a dyslexic group, a gifted-dyslexic group, and a borderline-dyslexic group (i.e., gifted children with relative literacy problems). Children were assessed on literacy, phonology, language, and working memory. Competing hypotheses were formulated, comparing the core-deficit view to the twice-exceptionality view on compensation with giftedness-related strengths. The results showed no indication of compensation of dyslexia-related deficits by giftedness-related strengths in gifted children with dyslexia. The higher literacy levels of borderline children compared to gifted children with dyslexia seemed the result of both fewer combinations of risk factors and less severe phonological deficits in this group. There was no evidence for compensation by specific strengths more relevant to literacy development in the borderline group. Accordingly, the findings largely supported the core-deficit view, whereas no evidence for the twice-exceptionality view was found. Besides practical implications, the findings also add to knowledge about the different manifestations of dyslexia and associated underlying cognitive factors at the higher end of the intelligence spectrum. PMID- 26269396 TI - EDA-ID and IP, two faces of the same coin: how the same IKBKG/NEMO mutation affecting the NF-kappaB pathway can cause immunodeficiency and/or inflammation. AB - Anhidrotic Ectodermal Dysplasia with ImmunoDeficiency (EDA-ID, OMIM 300291) and Incontinentia Pigmenti (IP, OMIM 308300) are two rare diseases, caused by mutations of the IKBKG/NEMO gene. The protein NEMO/IKKgamma is essential for the NF-kappaB activation pathway, involved in a variety of physiological and cellular processes, such as immunity, inflammation, cell proliferation, and survival. A wide spectrum of IKBKG/NEMO mutations have been identified so far, and, on the basis of their effect on NF-kappaB activation, they are considered hypomorphic or amorphic (loss of function) mutations. IKBKG/NEMO hypomorphic mutations, reducing but not abolishing NF-kappaB activation, have been identified in EDA-ID and IP patients. Instead, the amorphic mutations, abolishing NF-kappaB activation by complete IKBKG/NEMO gene silencing, cause only IP. Here, we present an overview of IKBKG/NEMO mutations in EDA-ID and IP patients and describe similarities and differences between the clinical/immunophenotypic and genetic aspects, highlighting any T and B lymphocyte defect, and paying particular attention to the cellular and molecular defects that underlie the pathogenesis of both diseases. PMID- 26269397 TI - Clinical and MRI responses to etanercept in early non-radiographic axial spondyloarthritis: 48-week results from the EMBARK study. AB - OBJECTIVE: To evaluate the efficacy and safety of etanercept (ETN) after 48 weeks in patients with early active non-radiographic axial spondyloarthritis (nr axSpA). METHODS: Patients meeting Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA, but not modified New York radiographic criteria, received double-blind ETN 50 mg/week or placebo (PBO) for 12 weeks, then open-label ETN (ETN/ETN or PBO/ETN). Clinical, health, productivity, MRI and safety outcomes were assessed and the 48-week data are presented here. RESULTS: 208/225 patients (92%) entered the open-label phase at week 12 (ETN, n=102; PBO, n=106). The percentage of patients achieving ASAS40 increased from 33% to 52% between weeks 12 and 48 for ETN/ETN and from 15% to 53% for PBO/ETN (within-group p value <0.001 for both). For ETN/ETN and PBO/ETN, the EuroQol 5 Dimensions utility score improved by 0.14 and 0.08, respectively, between baseline and week 12 and by 0.23 and 0.22 between baseline and week 48. Between weeks 12 and 48, MRI Spondyloarthritis Research Consortium of Canada sacroiliac joint (SIJ) scores decreased by -1.1 for ETN/ETN and by -3.0 for PBO/ETN, p<0.001 for both. Decreases in MRI SIJ inflammation and C-reactive protein correlated with several clinical outcomes at weeks 12 and 48. CONCLUSIONS: Patients with early active nr-axSpA demonstrated improvement from week 12 in clinical, health, productivity and MRI outcomes that was sustained to 48 weeks. TRIAL REGISTRATION NUMBER: NCT01258738. PMID- 26269398 TI - Disease activity in psoriatic arthritis (PsA): defining remission and treatment success using the DAPSA score. AB - BACKGROUND: The Disease Activity Index for Psoriatic Arthritis (DAPSA) is a valid and discriminative tool. Definitions of disease activity states and therapeutic response are still missing. We derived such criteria for the DAPSA. METHODS: We retrieved 30 patient profiles from an observational database including joint counts, patient pain and global activity ratings and C-reactive protein (CRP) and carried out a survey among experts to classify patients into remission (REM), low (LDA), moderate (MDA) or high (HDA) disease activity. Based on the distributions of DAPSA in each of these expert-assigned states we defined the cutpoints between groups. We performed similar analyses evaluating a clinical score (cDAPSA), omitting CRP. To define minor, moderate and major treatment response, we used Cohen's Kappa statistics and analysed agreement of DAPSA percentage change with ACR20/50/70-response in three randomised controlled trials. RESULTS: Our survey yielded a response rate of 75% (n=33). Mean DAPSA differed significantly between patients classified as REM, LDA, MDA or HDA (p<0.001). Based on the distributions of DAPSA in these groups, we propose cut-off values of <=4 for REM, >4 and <=14 for LDA, >14 and <=28 for MDA and >28 for HDA. We observed best agreement with ACR20/50/70-response at DAPSA changes of 50/75/85%, reflecting minor, moderate and major improvement. CONCLUSIONS: The DAPSA constitutes a disease-specific, validated and feasible tool for PsA assessment. In this study, we provide criteria for disease activity states and treatment response. They are based on an international expert survey, and show good performance in clinical trials and observational data. PMID- 26269399 TI - Systemic sclerosis-like histopathological features in the myocardium of uPAR deficient mice. AB - OBJECTIVE: Cardiomyopathy is among the leading causes of death from systemic sclerosis (SSc). Urokinase-type plasminogen activator receptor (uPAR)-deficient mice have been recently reported to display important histopathological hallmarks of SSc, including dermal fibrosis, reduced dermal capillary density, and pulmonary fibrosis. Here, we investigated whether uPAR-deficient mice could display the histopathological features of SSc-related cardiomyopathy. METHODS: Ventricular myocardial specimens from uPAR-deficient and wild-type mice at 12 and 24 weeks of age were analysed by both light microscopy and transmission electron microscopy. Picrosirius red staining and hydroxyproline content of myocardial specimens were quantified. Myofibroblast and microvessel counts were determined by immunofluorescence for alpha-smooth muscle actin and CD31, respectively. Endothelial cell apoptosis was assessed by a combined TUNEL/CD31 immunofluorescence assay. Expression of uPAR in human SSc and control ventricular myocardial autopsy specimens was determined by immunohistochemistry. RESULTS: The myocardium of 24-week-old uPAR-deficient mice displayed focal ischaemic lesions with cardiomyocyte hypertrophy, myofibril rarefaction and contraction band necrosis. At 24 weeks of age, interstitial and perivascular collagen deposition and myofibroblast counts were significantly greater in myocardial tissue of uPAR deficient mice than in wild-type mice. In uPAR-deficient mice, myocardial fibrosis was paralleled by microvascular endothelial cell apoptosis and reduced capillary density. uPAR expression was significantly downregulated in the myocardium of patients with SSc. CONCLUSIONS: Typical histopathological features of SSc-related cardiomyopathy are mimicked by uPAR-deficient mice. The downregulation of uPAR in the myocardium of patients with SSc may suggest similar underlying pathogenetic mechanisms. uPAR-deficient mice could be used as a preclinical model to study the mechanisms and therapeutic approaches of myocardial involvement in SSc. PMID- 26269400 TI - MicroRNA Replacing Oncogenic Klf4 and c-Myc for Generating iPS Cells via Cationized Pleurotus eryngii Polysaccharide-based Nanotransfection. AB - Induced pluripotent stem cells (iPSCs), resulting from the forced expression of cocktails out of transcription factors, such as Oct4, Sox2, Klf4, and c-Myc (OSKM), has shown tremendous potential in regenerative medicine. Although rapid progress has been made recently in the generation of iPSCs, the safety and efficiency remain key issues for further application. In this work, microRNA 302 367 was employed to substitute the oncogenic Klf4 and c-Myc in the OSKM combination as a safer strategy for successful iPSCs generation. The negatively charged plasmid mixture (encoding Oct4, Sox2, miR302-367) and the positively charged cationized Pleurotus eryngii polysaccharide (CPEPS) self-assembled into nanosized particles, named as CPEPS-OS-miR nanoparticles, which were applied to human umbilical cord mesenchymal stem cells for iPSCs generation after characterization of the physicochemical properties. The CPEPS-OS-miR nanoparticles possessed spherical shape, ultrasmall particle size, and positive surface charge. Importantly, the combination of plasmids Oct4, Sox2, and miR302 367 could not only minimize genetic modification but also show a more than 50 times higher reprogramming efficiency (0.044%) than any other single or possible double combinations of these factors (Oct4, Sox2, miR302-367). Altogether, the current study offers a simple, safe, and effective self-assembly approach for generating clinically applicable iPSCs. PMID- 26269401 TI - Barriers and Opportunities: A View across the Developmental Divide. PMID- 26269404 TI - Psoriasis and Cardiovascular Risk: Strength in Numbers Part 3. AB - Over the last decade a large body of epidemiological, translational, and animal model research has suggested that psoriasis may be a risk factor for cardiovascular and metabolic disease. Outcome based studies often suggest that patients with more severe psoriasis have an increased risk of major cardiovascular events independent of traditional risk factors that are captured in electronic health data. The study by Parisi and colleagues finds that incident severe psoriasis is associated with a non-statistically significant increased risk of major cardiovascular events, HR 1.28 (95% CI 0.96-1.69) in their primary model and a statistically significant increased risk, HR 1.46 (95% CI 1.11, 1.92), in a sensitivity analysis that excludes patients with inflammatory arthritis. These results are usefully consistent with prior studies published using the same or similar databases. Here we review three key biostatistical and epidemiological principles that are commonly misunderstood (over reliance on P values, confounding versus effect modification, and inception versus prevalent cohort design) and often lead to controversy in analyzing and interpreting results. PMID- 26269405 TI - Nanoparticles for Fidgety Cell Movement and Enhanced Wound Healing. AB - Complex spatiotemporal interaction of Rho GTPases with microtubules (MTs) and MT associated proteins drives directed cellular migration. In this issue, Charafeddine et al. describe a role for a novel MT-severing enzyme, fidgetin-like 2 (FL2), in directional migration of keratinocytes and fibroblasts. FL2 normally localizes to the leading edge of the cell cortex where it shears MTs, thus dictating the size and distribution of focal adhesions by regulating cytoskeletal remodeling. Small interfering RNA (siRNA)-directed knockdown of FL2 increases cell migration and focal adhesion area in vitro through possible interaction with Rho GTPases. Efficient FL2 knockdown in murine wounds was achieved using nanoparticles as a siRNA delivery vehicle, and this resulted in enhanced wound closure in vivo. Effective siRNA nanoparticle targeting of MT-severing enzymes offers promise of controlled and targeted delivery that may maximize therapeutic success for patients with burn wounds and chronic wound disorders. PMID- 26269406 TI - PLCG1 Gene Mutations in Cutaneous T-Cell Lymphomas Revisited. AB - The observation that mutations in the phospholipase C gamma 1 (PLCG1) gene (among which p.S345F was shown to be activating) are frequent (20%) in tumoral cutaneous T-cell lymphoma (CTCL) samples raised the possibility of targeting therapies against the PLCG1 signaling pathway. However, new data by Caumont et al. in this issue of JID show that PLCG1 mutations are far less prevalent than expected in CTCLs, which tempers the initial enthusiasm. This new study finds that only 3-5% of the CTCL tumor genomes (mycosis fungoides and Sezary syndrome) harbor PLCG1 mutations. PMID- 26269407 TI - Cells to Surgery Quiz: September 2015. PMID- 26269408 TI - September 2015 Snapshot Dx Quiz: Linking Science to Patient Care. PMID- 26269409 TI - Flow Cytometry II: Mass and Imaging Cytometry. PMID- 26269410 TI - Suboptimal push-out bond strengths of calcium silicate-based sealers. AB - AIM: To evaluate and compare the push-out bond strength of MTA Fillapex (Angelus, Londrina, Brazil) and iRoot SP (Innovative BioCeramix Inc., Vancouver, Canada) to the dentine walls of root canals. AH Plus (Dentsply DeTrey, Konstaz, Germany) and MTA (Angelus, Londrina, Brazil) were used as reference materials. METHODOLOGY: Sixty extracted human single-rooted teeth were selected. After standardized canal preparation and irrigation, the canals were dried with paper points and filled with one of four sealers: AH Plus, iRoot SP, MTA and MTA Fillapex. Roots were sectioned, and push-out tests were performed. The values of bond strength were analysed using the Kruskal-Wallis test. Mann-Whitney with Bonferroni correction was used to isolate the differences. The alpha-type error was set at 0.05 for the analyses. RESULTS: All specimens had measurable adhesion to root dentine and no premature failure occurred. There were significant differences amongst materials (P = 0.000). MTA-filled specimens had higher push-out bond strength values (P = 0.000). AH Plus had significantly higher bond strength than both Fillapex and iRoot SP (P = 0.000). Both Fillapex and iRoot SP had the lowest push-out bond strength amongst all experimental groups (P = 0.000). No difference occurred between the two calcium silicate-based root canal sealers (P = 0.265). CONCLUSION: The adhesion to root dentine associated with newer calcium silicate based sealers was compromised even when well-monitored laboratory conditions were used. PMID- 26269411 TI - Loss of NDRG2 enhanced activation of the NF-kappaB pathway by PTEN and NIK phosphorylation for ATL and other cancer development. AB - The activation of nuclear factor kappa B (NF-kappaB) signaling has a central role in the development of adult T-cell leukemia/lymphoma (ATL) and many other cancers. However, the activation mechanism of the NF-kappaB pathways remains poorly understood. Recently, we reported that N-myc downstream-regulated gene 2 (NDRG2) is a negative regulator of the phosphoinositide 3-kinase (PI3K)/AKT pathway by promoting the active dephosphorylated form of PTEN at its C-terminus via the recruitment of PP2A. Additionally, the down-regulation of NDRG2 expression promotes the inactive phosphorylated form of PTEN, which results in constitutively active PI3K/AKT signaling in various cancer cell types. Here, we investigated the involvement of NDRG2 in modulating NF-kappaB signaling. The forced expression of NDRG2 in ATL cells down-regulates not only the canonical pathway by inhibiting AKT signaling but also the non-canonical pathway by inducing NF-kappaB-inducing kinase (NIK) dephosphorylation via the recruitment of PP2A. Therefore, NDRG2 works as a PP2A recruiter to suppress not only PI3K/AKT signaling but also NF-kappaB signaling, which is particularly important in host defenses or immune responses to Human T-cell leukemia virus type 1 (HTLV-1) infection. Furthermore, the loss of NDRG2 expression might play an important role in the progression of tumor development after HTLV-1 infection. PMID- 26269412 TI - The multi-kinase inhibitor pazopanib targets hepatic stellate cell activation and apoptosis alleviating progression of liver fibrosis. AB - Tyrosine kinase inhibitors have been emerged recently as an effective therapy against liver fibrosis. The current study was designed to test a potential anti fibrotic effect of the multi-targeted receptor tyrosine kinase inhibitor pazopanib. Carbon tetrachloride (CCl4; 1 mL/kg) was injected intraperitoneally (i.p.) twice/week for 8 weeks. Pazopanib (10 and 30 mg/kg, i.p.) was administered three times/week at the beginning of week 5. Levels of liver function biomarkers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, and total bilirubin), malondialdehyde, transforming growth factor-beta1 (TGF-beta1), caspase-3, factor-related apoptosis (FAS), vascular endothelial growth factor (VEGF) receptor-1, and pigment endothelial derived factor (PEDF) were measured. The tissue level of the inflammatory cytokines IL-6 and tumor necrosis factor alpha (TNF-alpha) were assigned. Fibrotic area was measured by morphometry and expression of alpha-smooth muscle actin (alpha-SMA), caspase-3, platelet-derived growth factor (PDGF) receptor-beta, and matrix metalloproteinase-2 (MMP-2) was scored immunohistochemically. Hepatic expression of collagen-1-alpha-1 (Col1A1) and tissue inhibitor metalloproteinase-1 (TIMP-1) mRNA were assigned by RT-qPCR. Injection of CCl4 resulted in marked collagen deposition, necroinflammation, and fibrosis (2.67%). Pazopanib in a dose of 30 mg/kg improved liver function, reduced fibrosis (1.48%), and decreased significantly (P < 0.01) liver expression of malondialdehyde, TGF-beta1, IL-6, TNF-alpha, Col1A1, TIMP-1, alpha-SMA, MMP-2, PDGF receptor-beta, and VEGF receptor-1. Additionally, the apoptotic markers (caspase-3, FAS) and the anti-angiogenic factor PEDF were upregulated significantly (P < 0.05). Pazopanib at a certain dose level can halt liver fibrosis progression through modulating inflammatory cytokines, suppressing stellate cell activity, inducing apoptosis, and potentially regulating angiogenesis. PMID- 26269413 TI - Individual patient data network meta-analysis of mortality effects of implantable cardiac devices. AB - OBJECTIVE: Implantable cardioverter defibrillators (ICD), cardiac resynchronisation therapy pacemakers (CRT-P) and the combination therapy (CRT-D) have been shown to reduce all-cause mortality compared with medical therapy alone in patients with heart failure and reduced EF. Our aim was to synthesise data from major randomised controlled trials to estimate the comparative mortality effects of these devices and how these vary according to patients' characteristics. METHODS: Data from 13 randomised trials (12 638 patients) were provided by medical technology companies. Individual patient data were synthesised using network meta-analysis. RESULTS: Unadjusted analyses found CRT-D to be the most effective treatment (reduction in rate of death vs medical therapy: 42% (95% credible interval: 32-50%), followed by ICD (29% (20-37%)) and CRT-P (28% (15-40%)). CRT-D reduced mortality compared with CRT-P (19% (1-33%)) and ICD (18% (7-28%)). QRS duration, left bundle branch block (LBBB) morphology, age and gender were included as predictors of benefit in the final adjusted model. In this model, CRT-D reduced mortality in all subgroups (range: 53% (34 66%) to 28% (-1% to 49%)). Patients with QRS duration >=150 ms, LBBB morphology and female gender benefited more from CRT-P and CRT-D. Men and those <60 years benefited more from ICD. CONCLUSIONS: These data provide estimates for the mortality benefits of device therapy conditional upon multiple patient characteristics. They can be used to estimate an individual patient's expected relative benefit and thus inform shared decision making. Clinical guidelines should discuss age and gender as predictors of device benefits. PMID- 26269414 TI - The hormone-bound vitamin D receptor enhances the FBW7-dependent turnover of NF kappaB subunits. AB - Signaling by hormonal vitamin D, 1,25-dihydroxyvitamin D (1,25D) has attracted increasing interest because of its non-classical actions, particularly its putative anticancer properties and its role in controlling immune system function. Notably, the hormone-bound vitamin D receptor (VDR) suppresses signaling by pro-inflammatory NF-kappaB transcription factors, although the underlying mechanisms have remained elusive. Recently, the VDR was shown to enhance the turnover of the oncogenic transcription factor cMYC mediated by the E3 ligase and tumor suppressor FBW7. As FBW7 also controls the turnover of the p100 (NF-kappaB2) subunit of the family, we determined whether the 1,25D enhanced FBW7-dependent turnover of NF-kappaB subunits p100, p105 (NF-kappaB1) and p65 (RELA). Protein levels of all three subunits declined markedly in the presence of 1,25D in multiple cell lines in the absence of substantial changes in mRNA expression. The VDR coimmunoprecipitated with all three subunits, and 1,25D treatment accelerated subunit turnover in cycloheximide-treated cells. Importantly, we observed an association of FBW7 with p105 and p65, as well as p100, and knockdown of FBW7 eliminated 1,25D-dependent subunit turnover. Moreover, expression of NF-kappaB target genes was elevated in FBW7-depleted cells. These results reveal that 1,25D signaling suppresses NF-kappaB function by enhancing FBW7-dependent subunit turnover. PMID- 26269415 TI - Clinical outcomes of real-world patients treated with an amphilimus polymer-free stent versus new generation everolimus-eluting stents. AB - OBJECTIVES/BACKGROUND: To compare the 1-year clinical outcomes after implantation of the amphilimus, polymer-free stent (Cre8) versus new generation everolimus eluting stents (EESs) in a real-world patient registry. METHODS: A total of 187 consecutive patients treated with Cre8 between January 2011 and August 2013 in four Italian centers were included. These were propensity matched with 150 patients treated with new generation EES during the same period. Primary outcome was 1-year major adverse cardiovascular events (MACE), defined as all-cause death, myocardial infarction, and target vessel revascularization. RESULTS: Both groups had similar baseline characteristics, including diabetes (28% Cre8 vs. 27.3% EES, P = 0.972) and previous percutaneous coronary intervention (56% Cre8 vs. 58% EES, P = 0.726). There was a higher prevalence of B2/C lesions in the EES group (70.1% vs. 83.8%, P < 0.001). Total stent length per patient was similar. There were no significant differences in 1-year estimated MACE (7.4% Cre8 vs. 10.2% EES, P = 0.261), all-cause mortality (1.3% Cre8 vs. 1.4% EES, P = 0.823), target vessel revascularization (5.2% Cre8 vs. 8.8% EES, P = 0.169), and target lesion revascularization (3% Cre8 vs. 7.4% EES, P = 0.108) between the two groups. When adjusting for differences in baseline lesion characteristics, hazard ratio(Cre8/EES) for MACE was not significantly different between the two groups (0.75, 95% confidence interval 0.37-1.53, P(noninferiority) = 0.001, P(superiority) = 0.432). In patients with diabetes (Cre8, n = 42; EEE, n = 41), 1 year target lesion revascularization was 2.5% in the Cre8 group versus 14.6% in the EES group (P = 0.056). CONCLUSIONS: In a "real-world" patient registry, the Cre8 stent is associated with noninferior 1-year MACE rates compared with that of new generation EES. Trends of superior efficacy in patients with diabetes treated with Cre8 require further investigation. PMID- 26269416 TI - Regional analgesia for improvement of long-term functional outcome after elective large joint replacement. AB - BACKGROUND: Regional analgesia is more effective than conventional analgesia for controlling pain and may facilitate rehabilitation after large joint replacement in the short term. It remains unclear if regional anaesthesia improves functional outcomes after joint replacement beyond three months after surgery. OBJECTIVES: To assess the effects of regional anaesthesia and analgesia on long-term functional outcomes 3, 6 and 12 months after elective major joint (knee, shoulder and hip) replacement surgery. SEARCH METHODS: We performed an electronic search of several databases (CENTRAL, MEDLINE, EMBASE, CINAHL), and handsearched reference lists and conference abstracts. We updated our search in June 2015. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing regional analgesia versus conventional analgesia in patients undergoing total shoulder, hip or knee replacement. We included studies that reported a functional outcome with a follow-up of at least three months after surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We contacted study authors for additional information. MAIN RESULTS: We included six studies with 350 participants followed for at least three months. All of these studies enrolled participants undergoing total knee replacement. Studies were at least partially blinded. Three studies had a high risk of performance bias and one a high risk of attrition bias, but the risk of bias was otherwise unclear or low.Only one study assessed joint function using a global score. Due to heterogeneity in outcome and reporting, we could only pool three out of six RCTs, with range of motion assessed at three months after surgery used as a surrogate for joint function. All studies had a high risk of detection bias. Using the random-effects model, there was no statistically significant difference between the experimental and control groups (mean difference 3.99 degrees, 95% confidence interval (CI) - 2.23 to 10.21; P value = 0.21, 3 studies, 140 participants, very low quality evidence).We did not perform further analyses because immediate adverse effects were not part of the explicit outcomes of any of these typically small studies, and long-term adverse events after regional anaesthesia are rare.None of the included studies elicited or reported long-term adverse effects like persistent nerve damage. AUTHORS' CONCLUSIONS: More high-quality studies are needed to establish the effects of regional analgesia on function after major joint replacement, as well as on the risk of adverse events (falls). PMID- 26269417 TI - The compliance and burden of treatment with the epinephrine auto-injector in food allergic adolescents. AB - BACKGROUND: Food-allergic patients at high risk of potential fatal anaphylaxis should carry an epinephrine auto-injector (EAI) at all times. This treatment may be perceived as burdensome and this may affect compliance and health-related quality of life (HRQL). The aims of the study were (1) to determine the burden of treatment (BoT) of an EAI, (2) to examine the relationship between this burden and compliance, and (3) to analyze which factors contribute to the BoT of the EAI as perceived by food-allergic adolescents and their parents. METHODS: Dutch food allergic adolescents prescribed an EAI, and their parents completed a questionnaire package (n = 55). Relationships between BoT and HRQL, illness severity and perception, and anxiety measures were investigated. RESULTS: Food allergic adolescents and their parents were (extremely) positive about the EAI (54.5%; 72.7%, respectively) (=low BoT). The BoT measure showed a significantly greater burden in food-allergic adolescents prescribed an EAI who reported not carrying the EAI at all times than adolescents who reported they did. The BoT scores of both adolescents and their parents were not associated with HRQL, illness severity and perception, or trait anxiety. CONCLUSIONS: The majority of food-allergic adolescents and their parents were positive about the EAI (=low BoT). However, the BoT was significantly associated with self-reported compliance with carrying the EAI. The BoT was higher in food-allergic adolescents prescribed an EAI who reported not carrying the EAI at all times. The BoT measure seems to be a useful tool to study compliance with carrying an EAI. The BoT of an EAI is not associated with HRQL. The BoT measures a distinct concept related to compliance behavior. PMID- 26269419 TI - Uninsured rates drop dramatically in US states that embraced health reform law. PMID- 26269418 TI - Comparison of gabapentin versus topiramate on clinically affected dogs with Chiari-like malformation and syringomyelia. AB - To date there is no evidence-based data for efficacious treatment of neuropathic pain in dogs with Chiari-like malformation (CM) and syringomyelia (SM). The objective of this prospective cross-over study was to compare the effect of gabapentin versus topiramate, as an add-on treatment to carprofen, on quality of life (QoL) of dogs experiencing signs of neuropathic pain due to CM/SM. A visual analogue scale (VAS) was used to assess the QoL: (1) on day 0; (2) after 1 week of carprofen only; (3) after 2 weeks on carprofen and gabapentin; and (4) after 2 weeks on carprofen and topiramate. No significant difference was observed between VAS after gabapentin or topiramate (P=0.91). However, an improvement in QoL was observed when gabapentin was compared with baseline (P=0.009), but not for topiramate. In conclusion, the addition of gabapentin was more effective in improving QoL than carprofen alone, but the study failed to identify that gabapentin was more efficacious than topiramate. Perhaps the more favourable side effect profile of the former makes it more suitable for the treatment of neuropathic pain associated with CM/SM but further placebo-controlled trials are required to assess the efficacy of these drugs. PMID- 26269420 TI - Transition-metal-catalyzed hydrogen-transfer annulations: access to heterocyclic scaffolds. AB - The ability of hydrogen-transfer transition-metal catalysts, which enable increasingly rapid access to important structural scaffolds from simple starting materials, has led to a plethora of research efforts on the construction of heterocyclic scaffolds. Transition-metal-catalyzed hydrogen-transfer annulations are environmentally benign and highly atom-economical as they release of water and hydrogen as by-product and utilize renewable feedstock alcohols as starting materials. Recent advances in this field with respect to the annulations of alcohols with various nucleophilic partners, thus leading to the formation of heterocyclic scaffolds, are highlighted herein. PMID- 26269421 TI - A novel strategy to directly fabricate flexible hollow nanofibers with tunable luminescence-electricity-magnetism trifunctionality using one-pot electrospinning. AB - Novel photoluminescent-electrical-magnetic trifunctional flexible Eu(BA)3phen/PANI/Fe3O4/PVP (BA = benzoic acid, phen = phenanthroline, PANI = polyaniline, PVP = polyvinylpyrrolidone) hollow nanofibers were fabricated by a one-pot electrospinning technique using a specially designed coaxial spinneret for the first time. Very different from the traditional preparation process of hollow fibers via coaxial electrospinning, which needs to firstly fabricate the coaxial fibers and followed by removing the core through high-temperature calcination or solvent extraction, in our current study, no core spinning solution is used to directly fabricate hollow nanofibers. The morphology and properties of the obtained hollow nanofibers were characterized in detail using X ray diffractometry, scanning electron microscopy, transmission electron microscopy, fluorescence spectroscopy, Fourier-transform infrared spectroscopy, a 4-point probe resistivity measurement system and vibrating sample magnetometry. The Eu(BA)3phen/PANI/Fe3O4/PVP hollow nanofibers, with outer diameters of ca. 305 nm and inner diameters of about 140 nm, exhibit excellent photoluminescence performance, electrical conductivity and magnetic properties. Fluorescence emission peaks of Eu(3+) are observed in the Eu(BA)3phen/PANI/Fe3O4/PVP hollow nanofibers and assigned to the (5)D0->(7)F0 (580 nm), (5)D0->(7)F1 (592 nm) and (5)D0->(7)F2 (616 nm) energy level transitions of Eu(3+) ions, and the (5)D0 >(7)F2 hypersensitive transition at 616 nm is the predominant emission peak. The electrical conductivity of the hollow nanofibers reaches up to the order of 10( 3) S cm(-1). The luminescent intensity, electrical conductivity and magnetic properties of the hollow nanofibers can be tuned by adding various amounts of Eu(BA)3phen, PANI and Fe3O4 nanoparticles. The new-type photoluminescent electrical-magnetic trifunctional flexible hollow nanofibers hold potential for a variety of applications, including electromagnetic interference shielding, microwave absorption, molecular electronics and biomedicine. The design conception and synthetic strategy developed in this study are of universal significance to construct other multifunctional hollow one-dimensional nanomaterials. PMID- 26269422 TI - Gene expression profiling predicts pathways and genes associated with Parkinson's disease. AB - This study was aimed to explore the molecular mechanism of Parkinson's disease (PD) development and discover underlying pathways and genes associated with PD. The microarray data of GSE22491 containing 10 samples from PD patients and 8 samples from healthy controls (HC) were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by paired t-test. Then the DEGs were performed cluster and principal component analyses followed by Gene Ontology (GO) and pathway enrichment analyses and protein-protein interaction (PPI) network construction. Total 176 up-regulated DEGs and 49 down-regulated DEGs were identified. Totally, 39 GO terms and 72 pathways were closely related to PD. Pathway of neuronal system was enriched by 10 DEGs such as synapsin I (SYN1), glutamate receptor, ionotropic, N-methyl-D aspartate 1 (GRIN1) and GRIN2D. In the PPI networks, 18 hub genes were obtained, such as GRIN2D and discs, large (Drosophila) homolog-associated protein 3 (DLGAP3). The pathway of neuronal system and its enriched DEGs may play important roles in PD progression. The DEGs such as SYN1, GRIN1, GRIN2D and DLGAP3 may become promising candidate genes for PD. PMID- 26269423 TI - Low-grade cylindromatous adnexal carcinoma with unusual histopathological features: report of a case with comparative immunohistochemical study and meta analysis of the literature. AB - We present an extremely rare case of low-grade cylindromatous adnexal carcinoma (CAC) on the right chest wall of a 77-year-old man. Histopathologically, the neoplasm was initially diagnosed as a cylindroma that developed over the course of 13 years. A diagnosis of low-grade CAC was rendered after the documentation of a local recurrence and histopathology of the recurrent tumor. To further assess the evolution of low-grade CAC over time, we compared the morphology, mitotic account, proliferative markers and adhesion molecule immunoreactivity among paired primary and recurrent tumors. Unlike those earlier reported, our case showed the maintenance of tumor morphology after a recurrence without areas of obvious malignant transformation or metaplastic change. We showed here for the first time the expression of adhesion molecules of CAC/spiradenoma and a comparison of proliferation indices between a primary tumor and its local recurrence. This peculiar tumor differs from previously reported cases and harbors a malignant potential although the histopathological features of malignancy are subtle. Our meta-analysis of the literature provided background information regarding this rare entity. Alterations of E-cadherin and GCDFP-15 expression may provide additional helpful clues in differential diagnosis and determining the clinical behavior of this unusual neoplasm. Further studies are warranted to confirm the potential discriminative role of these markers. PMID- 26269424 TI - Plasmon-induced spatial electron transfer between single Au nanorods and ALD coated TiO2: dependence on TiO2 thickness. AB - We employed single-particle photoluminescence (PL) measurements to investigate the interfacial electron transfer between single Au nanorods (NRs) and TiO2 coated by ALD. Analyzing the energy relaxation path of plasmon-generated hot electrons as well as the PL intensities allowed for the detection and study of the interfacial electron transfer process spatially. PMID- 26269425 TI - Normal liver enzymes are correlated with severity of metabolic syndrome in a large population based cohort. AB - Key features of the metabolic syndrome are insulin resistance and diabetes. The liver as central metabolic organ is not only affected by the metabolic syndrome as non-alcoholic fatty liver disease (NAFLD), but may contribute to insulin resistance and metabolic alterations. We aimed to identify potential associations between liver injury markers and diabetes in the population-based Heinz Nixdorf RECALL Study. Demographic and laboratory data were analyzed in participants (n = 4814, age 45 to 75 y). ALT and AST values were significantly higher in males than in females. Mean BMI was 27.9 kg/m(2) and type-2-diabetes (known and unkown) was present in 656 participants (13.7%). Adiponectin and vitamin D both correlated inversely with BMI. ALT, AST, and GGT correlated with BMI, CRP and HbA1c and inversely correlated with adiponectin levels. Logistic regression models using HbA1c and adiponectin or HbA1c and BMI were able to predict diabetes with high accuracy. Transaminase levels within normal ranges were closely associated with the BMI and diabetes risk. Transaminase levels and adiponectin were inversely associated. Re-assessment of current normal range limits should be considered, to provide a more exact indicator for chronic metabolic liver injury, in particular to reflect the situation in diabetic or obese individuals. PMID- 26269426 TI - Analysis of epithelial-mesenchymal transition markers in psoriatic epidermal keratinocytes. AB - Psoriasis is similar to endpoints of epithelial-mesenchymal transition (EMT), a process of epithelial cells transformed into fibroblast-like cells. The molecular epithelial and mesenchymal markers were analysed in psoriatic keratinocytes. No obvious alteration of epithelial markers E-cadherin (E-cad), keratin 10 (K10), K14 and K16 was detected in psoriatic keratinocytes. However, significantly increased expression of Vim, FN, plasminogen activator inhibitor 1 (PAI-1) and Slug was seen. IL-17A and IL-13 at 50 ng ml(-1) strongly decreased expression of K10, Vim and FN. TGF-beta1 at 50 ng ml(-1) promoted the production of N-cad, Vim, FN and PAI-1. Slug was decreased by dexamethasone (Dex), but E-cad was upregulated by Dex. Silencing of ERK partially increased E-cad and K16, but remarkably inhibited K14, FN, Vim, beta-catenin, Slug and alpha5 integrin. Moreover, inhibition of Rho and GSK3 by their inhibitors Y27632 and SB216763, respectively, strongly raised E-cad, beta-catenin and Slug. Dex decreased Y27632 mediated increase of beta-catenin. Dex at 2.0 uM inhibited SB216763-regulated E cad, beta-catenin and slug. In conclusion, EMT in psoriatic keratinocytes may be defined as an intermediate phenotype of type 2 EMT. ERK, Rho and GSK3 play active roles in the process of EMT in psoriatic keratinocytes. PMID- 26269427 TI - Cytokines and growth factors cross-link heparan sulfate. AB - The glycosaminoglycan heparan sulfate (HS), present at the surface of most cells and ubiquitous in extracellular matrix, binds many soluble extracellular signalling molecules such as chemokines and growth factors, and regulates their transport and effector functions. It is, however, unknown whether upon binding HS these proteins can affect the long-range structure of HS. To test this idea, we interrogated a supramolecular model system, in which HS chains grafted to streptavidin-functionalized oligoethylene glycol monolayers or supported lipid bilayers mimic the HS-rich pericellular or extracellular matrix, with the biophysical techniques quartz crystal microbalance (QCM-D) and fluorescence recovery after photobleaching (FRAP). We were able to control and characterize the supramolecular presentation of HS chains--their local density, orientation, conformation and lateral mobility--and their interaction with proteins. The chemokine CXCL12alpha (or SDF-1alpha) rigidified the HS film, and this effect was due to protein-mediated cross-linking of HS chains. Complementary measurements with CXCL12alpha mutants and the CXCL12gamma isoform provided insight into the molecular mechanism underlying cross-linking. Fibroblast growth factor 2 (FGF-2), which has three HS binding sites, was also found to cross-link HS, but FGF-9, which has just one binding site, did not. Based on these data, we propose that the ability to cross-link HS is a generic feature of many cytokines and growth factors, which depends on the architecture of their HS binding sites. The ability to change matrix organization and physico-chemical properties (e.g. permeability and rigidification) implies that the functions of cytokines and growth factors may not simply be confined to the activation of cognate cellular receptors. PMID- 26269428 TI - Building a ninefold symmetrical barrel: structural dissections of centriole assembly. AB - Centrioles are short microtubule-based organelles with a conserved ninefold symmetry. They are essential for both centrosome formation and cilium biogenesis in most eukaryotes. A core set of five centriolar proteins has been identified and their sequential recruitment to procentrioles has been established. However, structures at atomic resolution for most of the centriolar components were scarce, and the underlying molecular mechanisms for centriole assembly had been a mystery--until recently. In this review, I briefly summarize recent advancements in high-resolution structural characterization of the core centriolar components and discuss perspectives in the field. PMID- 26269431 TI - Multiple apocrine poromas: a new case report. AB - Apocrine poromas are rare and distinctive benign adnexal neoplasms featuring tumor cells differentiating toward folliculosebaceous-apocrine units. We report an extremely rare case with multiple apocrine poromas in a single patient. Fifteen tumors were distributed on the head, neck, forearm and axilla of a 74 year-old man. All tumors were mostly composed of poroid cells that surrounded variably sized duct spaces, some of which exhibited decapitation secretion. The poroid cells were continuous with infundibulum-like structures that contained aggregates of mature sebocytes. The patient had no family history of similar tumors and no history of immunosuppressive therapy. This is the first report of multiple apocrine poromas, suggesting that predisposing genetic factors might play a part in the development of the tumors. PMID- 26269430 TI - In vivo mouse myocardial (31)P MRS using three-dimensional image-selected in vivo spectroscopy (3D ISIS): technical considerations and biochemical validations. AB - (31)P MRS provides a unique non-invasive window into myocardial energy homeostasis. Mouse models of cardiac disease are widely used in preclinical studies, but the application of (31)P MRS in the in vivo mouse heart has been limited. The small-sized, fast-beating mouse heart imposes challenges regarding localized signal acquisition devoid of contamination with signal originating from surrounding tissues. Here, we report the implementation and validation of three dimensional image-selected in vivo spectroscopy (3D ISIS) for localized (31)P MRS of the in vivo mouse heart at 9.4 T. Cardiac (31)P MR spectra were acquired in vivo in healthy mice (n = 9) and in transverse aortic constricted (TAC) mice (n = 8) using respiratory-gated, cardiac-triggered 3D ISIS. Localization and potential signal contamination were assessed with (31)P MRS experiments in the anterior myocardial wall, liver, skeletal muscle and blood. For healthy hearts, results were validated against ex vivo biochemical assays. Effects of isoflurane anesthesia were assessed by measuring in vivo hemodynamics and blood gases. The myocardial energy status, assessed via the phosphocreatine (PCr) to adenosine 5' triphosphate (ATP) ratio, was approximately 25% lower in TAC mice compared with controls (0.76 +/- 0.13 versus 1.00 +/- 0.15; P < 0.01). Localization with one dimensional (1D) ISIS resulted in two-fold higher PCr/ATP ratios than measured with 3D ISIS, because of the high PCr levels of chest skeletal muscle that contaminate the 1D ISIS measurements. Ex vivo determinations of the myocardial PCr/ATP ratio (0.94 +/- 0.24; n = 8) confirmed the in vivo observations in control mice. Heart rate (497 +/- 76 beats/min), mean arterial pressure (90 +/- 3.3 mmHg) and blood oxygen saturation (96.2 +/- 0.6%) during the experimental conditions of in vivo (31)P MRS were within the normal physiological range. Our results show that respiratory-gated, cardiac-triggered 3D ISIS allows for non invasive assessments of in vivo mouse myocardial energy homeostasis with (31)P MRS under physiological conditions. PMID- 26269429 TI - The roles of ERAS during cell lineage specification of mouse early embryonic development. AB - Eras encodes a Ras-like GTPase protein that was originally identified as an embryonic stem cell-specific Ras. ERAS has been known to be required for the growth of embryonic stem cells and stimulates somatic cell reprogramming, suggesting its roles on mouse early embryonic development. We now report a dynamic expression pattern of Eras during mouse peri-implantation development: its expression increases at the blastocyst stage, and specifically decreases in E7.5 mesoderm. In accordance with its expression pattern, the increased expression of Eras promotes cell proliferation through controlling AKT activation and the commitment from ground to primed state through ERK activation in mouse embryonic stem cells; and the reduced expression of Eras facilitates primitive streak and mesoderm formation through AKT inhibition during gastrulation. The expression of Eras is finely regulated to match its roles in mouse early embryonic development during which Eras expression is negatively regulated by the beta-catenin pathway. Thus, beyond its well-known role on cell proliferation, ERAS may also play important roles in cell lineage specification during mouse early embryonic development. PMID- 26269432 TI - Design of CID-cleavable protein cross-linkers: identical mass modifications for simpler sequence analysis. AB - The cross-linking Mass Spectrometry (XL-MS) technique has enormous potential for studying the interactions between proteins, and it can provide detailed structural information about the interaction interfaces in large protein complexes. Such information has been difficult to obtain by conventional structural methods. One of the primary impediments to the wider use of the XL-MS technique is the extreme challenge in sequencing cross-linked peptides because of their complex fragmentation patterns in MS. A recent innovation is the development of MS-cleavable cross-linkers, which allows direct sequencing of component peptides for facile identification. Sulfoxides are an intriguing class of thermally-cleavable compounds that have been shown to fragment selectively during low-energy collisional induced dissociation (CID) analysis. Current CID cleavable cross-linkers create fragmentation patterns in MS(2) of multiple peaks for each cross-linked peptide. Reducing the complexity of the fragmentation pattern in MS(2) facilitates subsequent MS(3) sequencing of the cross-linked peptides. The first authentic identical mass linker (IML) has now been designed, prepared, and evaluated. Multistage tandem mass spectrometry (MS(n)) analysis has demonstrated that the IML cross-linked peptides indeed yield one peak per peptide constituent in MS(2) as predicted, thus allowing effective and sensitive MS(3) analysis for unambiguous identification. Selective fragmentation for IML cross linked peptides from the 19S proteasome complex was observed, providing a proof of-concept demonstration for XL-MS studies on protein complexes. PMID- 26269434 TI - [A need to re-recognized the complement and kidney disease relationship]. PMID- 26269433 TI - Nitric Oxide-cGMP-PKG Pathway Acts on Orai1 to Inhibit the Hypertrophy of Human Embryonic Stem Cell-Derived Cardiomyocytes. AB - Cardiac hypertrophy is an abnormal enlargement of heart muscle. It frequently results in congestive heart failure, which is a leading cause of human death. Previous studies demonstrated that the nitric oxide (NO), cyclic GMP (cGMP), and protein kinase G (PKG) signaling pathway can inhibit cardiac hypertrophy and thus improve cardiac function. However, the underlying mechanisms are not fully understood. Here, based on the human embryonic stem cell-derived cardiomyocyte (hESC-CM) model system, we showed that Orai1, the pore-forming subunit of store operated Ca(2+) entry (SOCE), is the downstream effector of PKG. Treatment of hESC-CMs with an alpha-adrenoceptor agonist phenylephrine (PE) caused a marked hypertrophy, which was accompanied by an upregulation of Orai1. Moreover, suppression of Orai1 expression/activity using Orai1-siRNAs or a dominant negative construct Orai1(G98A) inhibited the hypertrophy, suggesting that Orai1 mediated SOCE is indispensable for the PE-induced hypertrophy of hESC-CMs. In addition, the hypertrophy was inhibited by NO and cGMP via activating PKG. Importantly, substitution of Ala for Ser(34) in Orai1 abolished the antihypertrophic effects of NO, cGMP, and PKG. Furthermore, PKG could directly phosphorylate Orai1 at Ser(34) and thus prevent Orai1-mediated SOCE. Together, we conclude that NO, cGMP, and PKG inhibit the hypertrophy of hESC-CMs via PKG mediated phosphorylation on Orai1-Ser-34. These results provide novel mechanistic insights into the action of cGMP-PKG-related antihypertrophic agents, such as NO donors and sildenafil. PMID- 26269435 TI - [Genetic basis of glomerulonephritis is gradually explored]. PMID- 26269436 TI - [Clinical hemodynamics: an explanation to therapy]. PMID- 26269437 TI - [Systolic blood pressure and progression of renal dysfunction in the elderly patients with moderate to severe chronic kidney disease: a cohort study from a tertiary hospital]. AB - OBJECTIVE: To study the effect of blood pressure (BP) control on the progression of renal function in elderly patients with chronic kidney disease ( CKD) stages 3 and 4. METHODS: Patients aged 65 years or older in our CKD clinic with baseline CKD stages 3 and 4 and with more than one-year followup until February 2014 were included in this study. Those who had an annual loss of epidermal growth factor receptor (eGFR) for more than 5 ml x min(-1) x 1.73 m(-2), or reached CKD stage 5, and/or initiated renal replacement therapy were regarded as progression of CKD. Cox regression was used to analyze the effect of BP control on the progression of CKD. Results A total of 118 patients [57 men, mean age (73.8 +/- 5.1) years] were enrolled in the final analysis with median baseline eGFR of 37.9 (29.3, 46.7) ml- min(-1.73) m(-2). The baseline BP was (137.0 +/- 18.0)/(72.5 +/- 10.3) mmHg (1 mmHg = 0.133 kPa). During the median 26 months (12-94 m) follow-up period, the average treated BP was (136.2 +/- 12.1)/ (70.5 +/- 6.9) mmHg. Among all the subjects, 64.4% of them reached the BP target (<140/90 mmHg) and 23.7% had progression of CKD. Treated systolic BP (HR = 1.504, 95% CI 1.023-2.212) and baseline eGFR (HR = 0.923, 95% CI 0.872-0.977) were independent risk factors for renal function progression in multivariate Cox analysis. Patients with treated systolic BP over 140 mmHg had higher risk to develop progression of CKD compared with those with systolic BP < or = 140 mmHg (HR = 2. 505, 95% CI 1.090-5.756). CONCLUSIONS: Tight blood pressure control is important in the routine care of elderly patients with CKD stage 3 and stage 4. PMID- 26269438 TI - [Diagnostic value of cystatin C in contrast-induced acute kidney injury after percutaneous coronary intervention]. AB - OBJECTIVE: To prospectively evaluate the value of cystatin C ( CysC) in diagnosis of contrast-induced acute kidney injury ( CIAKI) among patients undergoing Percutaneous Cardiovascular Intervention (PCI). METHODS: Patients who underwent PCI procedures in our hospital were enrolled. Serum creatinine (SCr) and CysC were measured at baseline before, 24 h and 48 h after PCI, respectively. CysC were examined by particle-enhanced turbidimetric immunoassay (PETIA). CIAKI was defined as a relative increase in SCr concentration of at least 25% or an absolute increase more than 44.8 mmol/L (0.5 mg/dl) within 48 h in the absence of other related causes. Results Among 196 patients, 135 were male and 61 female with a mean age of (70.4 +/- 11.3) years old. Twenty-nine (14. 8%) patients developed CIAKI according to the SCr criteria. The area under the ROC curve (AUC) at 24 h and 48 h post PCI were 0. 661 (95% CI 0.548-0.774, P = 0.006) and 0.783 (95% CI 0.701-0.865, P < 0.001), respectively. The diagnostic sensitivities of CysC at 24 h and 48 h were between 6.9% and 48.28%, while, the diagnostic specificities and negative predictive values of CysC were between 85.03%-97.60% and 85.79%-90.45%, respectively. The 15% elevation of 48 h CysC yielded the diagnostic sensitivity of 41.38%, specificity of 92.86%, negative predictive value of 90.17%, corrective rate of 85.28% with Youden Index of 0. 342 4. CONCLUSIONS: In this study, CysC presented an excellent diagnostic specificity and negative predictive value in diagnosis of CIAKI. It might be used as a tool for excluding CIAKI in clinical practice. 48 h CysC performed better than 24 h CysC in CIAKI diagnosis, among which a 15% increment achieved relatively the best diagnostic value. PMID- 26269439 TI - [The impact of glycosylated hemoglobin target value in treatment guidelines on glycemic control of type 2 diabetic in Chinese cities]. AB - OBJECTIVE: To investigate the influence of glycosylated hemoglobin Al c (HbA1c) standard value (2007 and 2010 Chinese Diabetes Prevention Guide) on glycemic control and treatment of type 2 diabetic patients in Chinese cities. METHODS: A cross-sectional study was carried out in type 2 diabetes mellitus from outpatients in selected hospitals all over China in 2009 and 2012. Patients treated with oral antidiabetic drugs (OADs), insulin or OAD combined with insulin were enrolled. A questionnaire including general characters, therapy, complications and blood glucose was completed by trained surveyors. RESULTS: A total of 30 853 patients were enrolled in 2009, and 48 232 patients in 2012. The distribution of HbAlc < 6.5%, 6.5% - <7.0%, 7.0% - <8.0%, 8.0% - <9.0%, 9.0% - <10.0% and > or = 10.0% was 20.35%, 12.59%, 35.50%, 18.94%, 6.46% and 6.16% in 2012; 14. 81%, 27.72%,14.55%, 6.55% and 8.36% in 2009, respectively. The top three OAD were biguanides, sulfonylureas and thiazolidine. The most common treatment options for combined therapy are metformin combined with sulfonylurea in both 2009 and 2012. CONCLUSIONS: There is an increase in the proportion of patients with good and general blood glucose control in 2012. With the generalization of Chinese Diabetes Prevention Guide, a steady tendency is presented in blood gluense control. PMID- 26269440 TI - [The impact of non-alcoholic fatty liver disease on islet function in type 2 diabetes]. AB - OBJECTIVE: To analyze the influence of hepatosteatosis on pancreatic P-cell function in type 2 diabetes mellitus (22DM). METHODS: A total of 213 subjects with T2DM from Metabolic Disease Hospital, Tianjin Medical University from January 2013 to December 2013 were included in the study. Non-alcoholic fatty liver disease (NAFLD) was diagnosed with abdominal ultrasonography. Patients were divided into two groups: 22DM with NAFLD and 22DM without NAFLD. ALT, AST, gamma glutamyltransferase, serum lipid, glycosylated hemoglobin A1c ( HbA1c), fructosamine, fasting glucose, insulin and 2 hours plasma glucose, insulin after 75g glucoseload were detected. The insulin resistance and P-cell function were assessed by HOMA-IR and HOMA-P. RESULTS: Among the 213 22DM subjects, 51% (108 cases) were with NAFLD. The HOMA-IR [4.76(2.83,7.21) vs. 2.79 (1.76, 4.37),P <0.05] and HOMA-P [49.18 (37.78, 85.09) vs. 29.50 (18.09, 45.54), P < 0.05] were significantly higher in 22DM with NAFLD than those in 22DM alone. Within subjects with 22DM and NAFLD,the HOMA-IR [6.28 (2.87, 8.17) vs. 2.95 (2.07, 3.66)P <0. 05] and HOMA-P [59.18 (37.78, 85.09) vs. 30.59 (28.56, 34.49), P < 0.05] levels were higher in subjects with normal liver function than those with abnormal liver function. CONCLUSIONS: T2DM patients with NAFLD have severer insulin resistance than those without NAFLD. The P-cell function of those patients was compensatory increased, which was decreased in subjects with abnormal liver function. PMID- 26269441 TI - [The clinical outcomes of thymectomy combined with radiotherapy or cyclophosphamide treatment for myasthenia gravis patients with thymoma]. AB - OBJECTIVE: To evaluate the therapeutic effects of thymectomy in myasthenia gravis (MG) patients with thymoma. METHODS: A total of 178 MG patients with thymectomy between July 2008 and December 2010 were included. All the subjects were received either cyclophosphamide alone or in combination with radiotherapeutic treatment after surgery. The MG absolute and relative clinical scores were used to assess the effectiveness of long-term treatments. Clinical evaluations were conducted before, and at 1 , 6, 12 and 24 months after operation. A comparative analysis on the inter-relationships among MG clinical presentation, WHO histology and Masaoka stage was also conducted. RESULTS: (1) Of the 178 thymoma-patients, 103 were male and 75 were female, with a mean age of (43.7 +/- 12.5)-years old. One hundred and twelve cases were taken cyclophosphamide, and 58 cases with invasive thymoma (stages II , III and IV or WHO type B3 ) were taken cyclophosphamide in combination with radiotherapy. Five patients refused cyclophosphamide or radiotherapy and 3 did not finish treatment. (2) The muscular strength improved obviously in 32.8% (58/177) of the patients after 1 month after thymectomy, and 59.8% (101/169), 69.7% (115/165) and 81.5% (132/162) after 6 months, 1 year and 2 years, respectively with MG score for disease severity decreased significantly with time. (3) No significant differences of the improvement rates were observed in patients within different WHO histology category. However, the rates were much higher in patients with Masaoka stage I (91.4%) and stage I (89.8%) than those in patients with stage III (45.5%) and IV (28.6%) (all P < 0.001) . CONCLUSIONS: The remission rate of MG patients with thymomas increase after thymectomy plus cyclophosphamide or in combination with radiotherapy and reached 81.5% after 2 years. The remission rate is associated with Masaoka stage, but not with WHO histology. PMID- 26269442 TI - [An analysis of clinical and imaging characteristics of atopic myelitis]. AB - OBJECTIVE: To study the clinical and imaging characteristics of Chinese atopic myelitis (AM) patients. METHODS: Three diagnosed AM patients were retrospectively analyzed for the clinical data, serum IgE level, antigen specific IgE, cerebrospinal fluid, spinal MRI and therapeutic efficacy profiles. RESULTS: All the three patients were male and presented as subacute AM with the onset at 25, 47 and 49 years old respectively. Two patients were allergic to pollen and other drugs, while another patient suffered from allergic rhinitis. Elevated serum total IgE and mite antigen specific IgE were found in all cases. Paraesthesia in limb extremities and positive Lhermitte sign were the main clinical features, while no optic, motor, urinary and defecation disturbance were found. Oligoclonal banding of cerebrospinal fluid and serum aquaporin 4 (AQP4) antibody were both negative in all cases. Spinal MRI showed lesions were hypointense on T1 and hyperintense on T2 at the posterior column of T2-3 segment with abnormal enhancement in case 1, hypointense on T1 and hyperintense on T2 at C2/3 segment with mild swelling in case 2 and hypointense on T1 and hyperintense on T2 at C3-5 segments with swelling and abnormal enhancement in case 3. Vitamin B were used in one patient, while the other two patients improved after the treatment with high dose corticosteroids. CONCLUSIONS: Subacute myelitis predominantly presents as paraesthesia in limb extremities with elevated serum total IgE and mite antigen specific IgE, while severe motor disorders are rare. Swelling and abnormal enhancement lesions at the posterior column of cervical cord are the common imaging features. Treatment with corticosteroids is recommended to be sustained for 3-6 months. PMID- 26269443 TI - [An analysis of amino acid metabolic profile and its clinical significance in ulcerative colitis]. AB - OBJECTIVE: To determine the relationship between serum amino acid composition and pathogenesis of ulcerative colitis ( UC) , so as to explore some new biomarkers for early diagnosis and treatment. METHODS: This study was conducted in the 309 Hospital of Chinese People's Liberation Army between October 2012 and November 2013. Forty-four UC patients and 52 healthy controls were enrolled and the serum samples were collected. Using high performance liquid chromatography-mass spectrometry technology (HPLC-MS/MS) stable isotope internal standard method, we detected serum amino acid metabolic profiling in the two groups. RESULTS: Compared with the control group, the serum levels of glutamic acid, glutamine, methionine, tryptophan and histidine in UC group were significantly lower [(59.20 +/- 21.93) mol/L vs. (88.14 +/- 34.85) micromol/L; (2200.51 +/- 648.03) [mol/L vs. (2 664.91 +/- 1034.74) micromol/L;(268.69 +/- 211.64) micromol/L vs. (431.48 +/- 298.00) micromol/L; (68.83 +/- 32.33) [mol/L vs. (89.96 +/- 29.29) micromol/L; (101.88 +/- 32.01) micromol/L vs. (115.10 +/- 17.84) micromol/L respectively, all P < 0.05 ]. However, the serum levels of asparagine and isoleucine in UC group were significantly higher than the control group [(195.14 +/- 122.14) micromol/L vs. (140.49 +/- 34.91) micromol/L; (94.61 +/- 29.76) micromol/L vs. (80.99 +/- 19.73) [micromol/L respectively; both P < 0.05]. CONCLUSION: The amino acid metabolic profiling in UC patients is different from that in healthy controls, which suggests that there might be a certain relationship between amino acid composition and pathogenesis of UC. Some amino acids would be tested as potential biomarkers in patients with UC. PMID- 26269444 TI - [The effects and mechanism of islet amyloid polypeptide on insulin secretion in INS-1 cells stimulated by glibenclamide]. AB - OBJECTIVE: To observe the effects, and study the mechanism of islet amyloid polypeptide (IAPP) on insulin secretion in INS-1 cells stimulated by glibenclamide. METHODS: Whole cell patch clamp technique was employed to study the influences of short exposure to IAPP on electrophysiological characteristics of ATP-sensitive K+ channel (K(ATP) channel) upon sulfonylurea stimulation. Intracellular free calcium changes in this process was observed by laser scanning confocal microscope. Insulin was measured by enzyme-linked immunoassay. RESULTS: (1) Insulin secretion stimulated by 1 micomol/L glibenclamide was significantly decreased from (11.43 +/- 1.22) microg/L to (9.40 +/- 0.87) microg/L and to (7.11 +/- 1.85) microg/L after 1 micromol/L and 10 micromol/L IAPP incubation, respectively. (2) Glibenclamide-stimulated calcium influx was dose dependently inhibited by IAPP from 1 micromol/L to 10 micromol/L, with the AUC of fluorescence intensity-time reduced from 427.78 +/- 2.32 to 380.59 +/- 1.49, and to 246.53 +/- 8.41, respectively. (3) Compared with that in control cells (14.59 +/- 0.69) mV, the half activation voltage of KA, channel in response to glibenclamide was significantly increased to (28.75 +/- 0.77) mV and to (46.95 +/ 1.81) mV in cells pretreated with 1 micromol/L and 10 micromol/L IAPP, implicating an inhibitory effect of IAPP on activation of K(ATP) channel. CONCLUSION: Short-term exposure to high concentration of IAPP inhibited glibenclamide-induced closure of K(ATP) channels and decreased calcium influx, which may ultimately lead to the reduction of insulin secretion in INS-1 cells PMID- 26269445 TI - Efficacy and safety of femtosecond laser-assisted cataract surgery versus conventional phacoemulsification for cataract: a meta-analysis of randomized controlled trials. AB - The aim of this study was to evaluate the efficacy and safety of femtosecond laser-assisted cataract surgery (FLACS) versus conventional phacoemulsification cataract surgery (CPCS) in the treatment of cataract. Randomized controlled trials (RCTs) were searched in PubMed, Embase and the Cochrane Central Register of Controlled Trials. Nine qualified studies with a total of 989 eyes were included. Compared with CPCS, FLACS significantly reduced mean phaco energy and effective phacoemulsification time (EPT) required in the surgery. Central corneal thickness (CCT) was significantly lower in FLACS at 1 day of follow-up, but CCT and corneal endothelial cells count was comparable at 1 week of follow-up or longer. FLACS achieved a better visual outcome at postoperative 1 week and 6 months, but the difference was not significant at postoperative 1-3 months. Regard to surgical complications, the incidences of intraoperative anterior capsule tear, postoperative macular edema and elevated intraocular pressure were similar. In conclusion, femtosecond laser pretreatment can reduce phaco energy and EPT, which may reduce the heat damage to ocular tissues by ultrasound. This novel technique might be beneficial for patients with dense cataract and/or low preoperative endothelial cell values. Well-designed RCTs with longer follow-up are still necessary to provide more reliable evidence. PMID- 26269446 TI - Evaluation of gait symmetry in poliomyelitis subjects: Comparison of a conventional knee-ankle-foot orthosis and a new powered knee-ankle-foot orthosis. AB - BACKGROUND: Compared to able-bodied subjects, subjects with post-polio syndrome and poliomyelitis demonstrate a preference for weight-bearing on the non-paretic limb, causing gait asymmetry. OBJECTIVES: The purpose of this study was to evaluate the gait symmetry of the poliomyelitis subjects when ambulating with either a drop-locked knee-ankle-foot orthosis or a newly developed powered knee ankle-foot orthosis. STUDY DESIGN: Quasi experimental study. METHODS: Seven subjects with poliomyelitis who routinely wore conventional knee-ankle-foot orthoses participated in this study and received training to enable them to ambulate with the powered knee-ankle-foot orthosis on level ground, prior to gait analysis. RESULTS: There were no significant differences in the gait symmetry index of step length (p = 0.085), stance time (p = 0.082), double-limb support time (p = 0.929), or speed of walking (p = 0.325) between the two test conditions. However, using the new powered knee-ankle-foot orthosis improved the symmetry index in step width (p = 0.037), swing time (p = 0.014), stance phase percentage (p = 0.008), and knee flexion during swing phase (p ? 0.001) compared to wearing the drop-locked knee-ankle-foot orthosis. CONCLUSION: The use of a powered knee-ankle-foot orthosis for ambulation by poliomyelitis subjects affects gait symmetry in the base of support, swing time, stance phase percentage, and knee flexion during swing phase. CLINICAL RELEVANCE: A new powered knee-ankle foot orthosis can improve gait symmetry for poliomyelitis subjects by influencing step width, swing time, stance time percentage, and knee flexion during swing phase when compared to ambulating with a drop-locked knee-ankle-foot orthosis. PMID- 26269447 TI - Effect of regional muscle location but not adiposity on mitochondrial biogenesis regulating proteins. AB - PURPOSE: The aim of this study was to determine if the expression of the mitochondrial biogenesis-regulating proteins SIRT1, SIRT3 and PGC-1alpha in human skeletal muscle is influenced by adiposity. METHOD: Twenty-nine male subjects were recruited into three groups: control (n = 10), obese (n = 10) and post-obese (n = 9). Intentionally, groups were matched by age, aerobic capacity and in addition the control and post-obese groups also by BMI. Muscle biopsies were obtained from the m. deltoid and vastus lateralis. PGC-1alpha, SIRT1 and SIRT3 protein expression was analyzed by Western blot. RESULT: PGC-1alpha, SIRT1 and SIRT3 protein expression was similar regardless of the level of adiposity. Only a main effect of group on SIRT1 protein showed a trend toward higher expression in post-obese than control and obese (P = 0.09). Despite similar muscle fiber-type composition (previously reported), PGC-1alpha, SIRT1 and SIRT3 protein expression was higher in leg compared to arm muscle in all groups (P < 0.05). CONCLUSION: This study shows that PGC-1alpha, SIRT1 and SIRT3 protein expression in basal conditions was not altered in humans with different levels of adiposity but similar aerobic capacity. The expression of PGC-1alpha, SIRT1 and SIRT3 was higher in vastus lateralis than in deltoid muscle, indicating that local rather than systemic factors prevail in regulating the level of expression of these proteins. PMID- 26269448 TI - Circadian variation of salivary immunoglobin A, alpha-amylase activity and mood in response to repeated double-poling sprints in hypoxia. AB - PURPOSE: To assess the circadian variations in salivary immunoglobin A (sIgA) and alpha-amylase activity (sAA), biomarkers of mucosal immune function, together with mood during 2 weeks of repeated sprint training in hypoxia (RSH) and normoxia (RSN). METHODS: Over a 2-week period, 17 competitive cross-country skiers performed six training sessions, each consisting of four sets of five 10-s bouts of all-out double-poling under either normobaric hypoxia (FiO2: 13.8%, 3000 m) or normoxia. The levels of sIgA and sAA activity and mood were determined five times during each of the first (T1) and sixth (T6) days of training, as well as during days preceding (baseline) and after the training intervention (follow-up). RESULTS: With RSH, sIgA was higher on T6 than T1 (P = 0.049), and sAA was increased on days T1, T6, and during the follow-up (P < 0.01). With RSN, sIgA remained unchanged and sAA was elevated on day T1 only (P = 0.04). Similarly, the RSH group demonstrated reduced mood on days T1, T6, and during the follow-up, while mood was lowered only on T1 with RSN (P < 0.01). CONCLUSIONS: The circadian variation of sIgA and sAA activity, biomarkers of mucosal immune function, as well as mood were similar on the first day of training when repeated double poling sprints were performed with or without hypoxia. Only with RSH did the levels of sIgA and sAA activity rise with time, becoming maximal after six training sessions, when mood was still lowered. Therefore, six sessions of RSH reduced mood, but did not impair mucosal immune function. PMID- 26269449 TI - Recommendations for somatic and germline genetic testing of single pheochromocytoma and paraganglioma based on findings from a series of 329 patients. AB - BACKGROUND: Nowadays, 65-80% of pheochromocytoma and paraganglioma (PPGL) cases are explained by germline or somatic mutations in one of 22 genes. Several genetic testing algorithms have been proposed, but they usually exclude sporadic PPGLs (S-PPGLs) and none include somatic testing. We aimed to genetically characterise S-PPGL cases and propose an evidence-based algorithm for genetic testing, prioritising DNA source. METHODS: The study included 329 probands fitting three criteria: single PPGL, no syndromic and no PPGL family history. Germline DNA was tested for point mutations in RET and for both point mutation and gross deletions in VHL, the SDH genes, TMEM127, MAX and FH. 99 tumours from patients negative for germline screening were available and tested for RET, VHL, HRAS, EPAS1, MAX and SDHB. RESULTS: Germline mutations were found in 46 (14.0%) patients, being more prevalent in paragangliomas (PGLs) (28.7%) than in pheochromocytomas (PCCs) (4.5%) (p=6.62*10(-10)). Somatic mutations were found in 43% of those tested, being more prevalent in PCCs (48.5%) than in PGLs (32.3%) (p=0.13). A quarter of S-PPGLs had a somatic mutation, regardless of age at presentation. Head and neck PGLs (HN-PGLs) and thoracic-PGLs (T-PGLs) more commonly had germline mutations (p=2.0*10(-4) and p=0.027, respectively). Five of the 29 metastatic cases harboured a somatic mutation, one in HRAS. CONCLUSIONS: We recommend prioritising testing for germline mutations in patients with HN-PGLs and T-PGLs, and for somatic mutations in those with PCC. Biochemical secretion and SDHB-immunohistochemistry should guide genetic screening in abdominal-PGLs. Paediatric and metastatic cases should not be excluded from somatic screening. PMID- 26269450 TI - Advanced glycation end-products inhibit mesenchymal-epidermal interaction by up regulating proinflammatory cytokines in hair follicles. PMID- 26269451 TI - Radial artery occlusion and hand strength after percutaneous coronary procedures: Results of the HANGAR study. AB - OBJECTIVES: The aim of this prospective study was to evaluate muscle force of the hand, thumb, and forefinger in patients with prolonged radial occlusion after transradial percutaneous coronary procedures. BACKGROUND: There are no data on hand strength and function in patients with prolonged radial occlusion after percutaneous coronary procedures. METHODS: Elective patients with chronic stable angina undergoing percutaneous coronary procedures were evaluated the day before the procedure for radial artery patency, Allen test, hand grip, and thumb and forefinger pinch tests. The same measures were performed the day after the procedure and at follow-up. At follow-up, patients were divided in two groups according to the radial patency (group 1) or occlusion (group 2). RESULTS: Of the 99 patients included in the study, 90 patients had a patent radial artery (group 1), and nine (9.1%) patients had an occluded artery (group 2). At baseline, there were no significant differences in hand grip test between the two groups (42 +/- 11 kg in group 1 and 41 +/- 17 kg in group 2, P = 0.74). In both groups, after the procedure, the hand grip test values was significantly reduced compared with baseline values (40 +/- 11 kg in group 1, P < 0.0001 and 37 +/- 17 kg in group 2, P = 0.007). Finally, at follow-up, in both groups, the hand grip test values returned to baseline values. Thumb and forefinger pinch tests did not show significant differences after the procedure and at follow-up, compared with baseline. CONCLUSIONS: Radial artery occlusion after percutaneous coronary procedures was not associated with a reduction in hand and finger strength. PMID- 26269453 TI - Chemically Patterned Inverse Opal Created by a Selective Photolysis Modification Process. AB - Anisotropic photonic crystal materials have long been pursued for their broad applications. A novel method for creating chemically patterned inverse opals is proposed here. The patterning technique is based on selective photolysis of a photolabile polymer together with postmodification on released amine groups. The patterning method allows regioselective modification within an inverse opal structure, taking advantage of selective chemical reaction. Moreover, combined with the unique signal self-reporting feature of the photonic crystal, the fabricated structure is capable of various applications, including gradient photonic bandgap and dynamic chemical patterns. The proposed method provides the ability to extend the structural and chemical complexity of the photonic crystal, as well as its potential applications. PMID- 26269452 TI - Intestinal macrophages arising from CCR2(+) monocytes control pathogen infection by activating innate lymphoid cells. AB - Monocytes play a crucial role in antimicrobial host defence, but the mechanisms by which they protect the host during intestinal infection remains poorly understood. Here we show that depletion of CCR2(+) monocytes results in impaired clearance of the intestinal pathogen Citrobacter rodentium. After infection, the de novo recruited CCR2(+) monocytes give rise to CD11c(+)CD11b(+)F4/80(+)CD103(-) intestinal macrophages (MPs) within the lamina propria. Unlike resident intestinal MPs, de novo differentiated MPs are phenotypically pro-inflammatory and produce robust amounts of IL-1beta (interleukin-1beta) through the non canonical caspase-11 inflammasome. Intestinal MPs from infected mice elicit the activation of RORgammat(+) group 3 innate lymphoid cells (ILC3) in an IL-1beta dependent manner. Deletion of IL-1beta in blood monocytes blunts the production of IL-22 by ILC3 and increases the susceptibility to infection. Collectively, these studies highlight a critical role of de novo differentiated monocyte derived intestinal MPs in ILC3-mediated host defence against intestinal infection. PMID- 26269454 TI - Field comparison of tolerance of a collar containing 10.0% imidacloprid/4.5% flumethrin (Seresto) and a placebo collar placed on cats. AB - OBJECTIVES: A collar containing 10.0% imidacloprid/4.5% flumethrin (Seresto; Bayer Animal Health) controls flea and tick infestations for 8 months and is effective in preventing transmission of Bartonella henselae and Cytauxzoon felis among cats. The purpose of this study was to compare tolerance of client-owned cats for the 10.0% imidacloprid/4.5% flumethrin collar or a physically identical placebo collar. METHODS: A total of 96 client-owned cats were enrolled in the study. Cats that were systemically ill, of hairless breed or declawed in all four limbs were excluded. Cats were randomized by household to wear a placebo collar for 14 days followed by the 10.0% imidacloprid/4.5% flumethrin collar for 14 days or the 10.0% imidacloprid/4.5% flumethrin collar for 28 days. Examinations by a veterinarian were performed on days 0, 14 and 28. Owners recorded daily systemic and local health observations. RESULTS: All but two cats, including one that entrapped the mandible in the collar and one that developed local pyodermatitis (10.0% imidacloprid/4.5% flumethrin collar), completed the 28 day study. The majority of the local lesions or licking associated with the collars occurred in the first 14 days, and licking (but not skin lesions) was more common in cats wearing the 10.0% imidacloprid/4.5% flumethrin collars. No local lesions were reported for placebo cats after switching to the 10.0% imidacloprid/4.5% flumethrin collar, and only one cat wearing the 10.0% imidacloprid/4.5% flumethrin collar had reports of licking after day 14. Housing status, single or multiple cat household, and whether a collar had been worn previously were not associated with side effects. CONCLUSIONS AND RELEVANCE: Adverse events detected for cats wearing 10.0% imidacloprid/4.5% flumethrin collars were similar to those for cats wearing placebo collars and to cats wearing identification collars in a separate study. The data suggest that most cats originally intolerant of collars become receptive over time. PMID- 26269455 TI - Evaluation of intranasal vaccine administration and high-dose interferon- alpha2b therapy for treatment of chronic upper respiratory tract infections in shelter cats. AB - Clinical signs of upper respiratory tract infection can be hard to manage in cats, particularly those in shelters. In this study, clinical data were collected from chronically ill (3-4 weeks' duration) cats with suspected feline herpesvirus 1 (FHV-1) or feline calicivirus (FCV) infections after administration of one of two novel therapies. Group A cats were administered a commercially available formulation of human interferon-alpha2b at 10,000 U/kg subcutaneously for 14 days, and group B cats were administered one dose of a FHV-1 and FCV intranasal vaccine. Molecular assays for FHV-1 and FCV were performed on pharyngeal samples, and a number of cytokines were measured in the blood of some cats. A clinical score was determined daily for 14 days, with cats that developed an acceptable response by day 14 returning to the shelter for adoption. Those failing the first treatment protocol were entered into the alternate treatment group. During the first treatment period, 8/13 cats in group A (61.5%) and all 12 cats in group B (100%) had apparent responses. The seven cats positive for nucleic acids of FHV-1 or FCV responded favorably, independent of the treatment group. There were no differences in cytokine levels between cats that responded to therapy or failed therapy. Either protocol assessed here may be beneficial in alleviating chronic clinical signs of suspected feline viral upper respiratory tract disease in some cats that have failed other, more conventional, therapies. The results of this study warrant additional research involving these protocols. PMID- 26269456 TI - The IMiDs targets IKZF-1/3 and IRF4 as novel negative regulators of NK cell activating ligands expression in multiple myeloma. AB - Immunomodulatory drugs (IMiDs) have potent anti-tumor activities in multiple myeloma (MM) and are able to enhance the cytotoxic function of natural killer (NK) cells, important effectors of the immune response against MM. Here, we show that these drugs can enhance the expression of the NKG2D and DNAM-1 activating receptor ligands MICA and PVR/CD155 in human MM cell lines and primary malignant plasma cells. Depletion of cereblon (CRBN) by shRNA interference strongly impaired upregulation of these ligands and, more interestingly, IMiDs/CRBN mediated downregulation of the transcription factors Ikaros (IKZF1), Aiolos (IKZF3) and IRF4 was critical for these regulatory mechanisms. Indeed, shRNA knockdown of IKZF1 or IKZF3 expression was both necessary and sufficient for the upregulation of MICA and PVR/CD155 expression, suggesting that these transcription factors can repress these genes; accordingly, the direct interaction and the negative role of IKZF1 and IKZF3 proteins on MICA and PVR/CD155 promoters were demonstrated. Finally, MICA expression was enhanced in IRF4-silenced cells, indicating a specific suppressive role of this transcription factor on MICA gene expression in MM cells.Taken together, these findings describe novel molecular pathways involved in the regulation of MICA and PVR/CD155 gene expression and identify the transcription factors IKZF-1/IKZF-3 and IRF4 as repressors of these genes in MM cells. PMID- 26269457 TI - O-GlcNAcase overexpression reverses coronary endothelial cell dysfunction in type 1 diabetic mice. AB - Cardiovascular disease is the primary cause of morbidity and mortality in diabetes, and endothelial dysfunction is commonly seen in these patients. Increased O-linked N-acetylglucosamine (O-GlcNAc) protein modification is one of the central pathogenic features of diabetes. Modification of proteins by O-GlcNAc (O-GlcNAcylation) is regulated by two key enzymes: beta-N-acetylglucosaminidase [O-GlcNAcase (OGA)], which catalyzes the reduction of protein O-GlcNAcylation, and O-GlcNAc transferase (OGT), which induces O-GlcNAcylation. However, it is not known whether reducing O-GlcNAcylation can improve endothelial dysfunction in diabetes. To examine the effect of endothelium-specific OGA overexpression on protein O-GlcNAcylation and coronary endothelial function in diabetic mice, we generated tetracycline-inducible, endothelium-specific OGA transgenic mice, and induced OGA by doxycycline administration in streptozotocin-induced type 1 diabetic mice. OGA protein expression was significantly decreased in mouse coronary endothelial cells (MCECs) isolated from diabetic mice compared with control MCECs, whereas OGT protein level was markedly increased. The level of protein O-GlcNAcylation was increased in diabetic compared with control mice, and OGA overexpression significantly decreased the level of protein O-GlcNAcylation in MCECs from diabetic mice. Capillary density in the left ventricle and endothelium-dependent relaxation in coronary arteries were significantly decreased in diabetes, while OGA overexpression increased capillary density to the control level and restored endothelium-dependent relaxation without changing endothelium-independent relaxation. We found that connexin 40 could be the potential target of O-GlcNAcylation that regulates the endothelial functions in diabetes. These data suggest that OGA overexpression in endothelial cells improves endothelial function and may have a beneficial effect on coronary vascular complications in diabetes. PMID- 26269458 TI - Autonomous requirements of the Menkes disease protein in the nervous system. AB - Menkes disease is a fatal neurodegenerative disorder arising from a systemic copper deficiency caused by loss-of-function mutations in a ubiquitously expressed copper transporter, ATP7A. Although this disorder reveals an essential role for copper in the developing human nervous system, the role of ATP7A in the pathogenesis of signs and symptoms in affected patients, including severe mental retardation, ataxia, and excitotoxic seizures, remains unknown. To directly examine the role of ATP7A within the central nervous system, we generated Atp7a(Nes) mice, in which the Atp7a gene was specifically deleted within neural and glial cell precursors without impairing systemic copper homeostasis, and compared these mice with the mottled brindle (mo-br) mutant, a murine model of Menkes disease in which Atp7a is defective in all cells. Whereas mo-br mice displayed neurodegeneration, demyelination, and 100% mortality prior to weaning, the Atp7a(Nes) mice showed none of these phenotypes, exhibiting only mild sensorimotor deficits, increased anxiety, and susceptibility to NMDA-induced seizure. Our results indicate that the pathophysiology of severe neurological signs and symptoms in Menkes disease is the result of copper deficiency within the central nervous system secondary to impaired systemic copper homeostasis and does not arise from an intrinsic lack of ATP7A within the developing brain. Furthermore, the sensorimotor deficits, hypophagia, anxiety, and sensitivity to NMDA-induced seizure in the Atp7a(Nes) mice reveal unique autonomous requirements for ATP7A in the nervous system. Taken together, these data reveal essential roles for copper acquisition in the central nervous system in early development and suggest novel therapeutic approaches in affected patients. PMID- 26269460 TI - Using Active Learning to Teach Concepts and Methods in Quantitative Biology. AB - This article provides a summary of the ideas discussed at the 2015 Annual Meeting of the Society for Integrative and Comparative Biology society-wide symposium on Leading Students and Faculty to Quantitative Biology through Active Learning. It also includes a brief review of the recent advancements in incorporating active learning approaches into quantitative biology classrooms. We begin with an overview of recent literature that shows that active learning can improve students' outcomes in Science, Technology, Engineering and Math Education disciplines. We then discuss how this approach can be particularly useful when teaching topics in quantitative biology. Next, we describe some of the recent initiatives to develop hands-on activities in quantitative biology at both the graduate and the undergraduate levels. Throughout the article we provide resources for educators who wish to integrate active learning and technology into their classrooms. PMID- 26269459 TI - Directional migration and transcriptional analysis of oligodendrocyte precursors subjected to stimulation of electrical signal. AB - Loss of oligodendrocytes as the result of central nervous system disease causes demyelination that impairs axon function. Effective directional migration of endogenous or grafted oligodendrocyte precursor cells (OPCs) to a lesion is crucial in the neural remyelination process. In this study, the migration of OPCs in electric fields (EFs) was investigated. We found that OPCs migrated anodally in applied EFs, and the directedness and displacement of anodal migration increased significantly when the EF strength increased from 50 to 200 mV/mm. However, EFs did not significantly affect the cell migration speed. The transcriptome of OPCs subjected to EF stimulation (100 and 200 mV/mm) was analyzed using RNA sequencing (RNA-Seq), and results were verified by the reverse transcription quantitative polymerase chain reaction. A Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the mitogen-activated protein kinase pathway that signals cell migration was significantly upregulated in cells treated with an EF of 200 mV/mm compared with control cells. Gene ontology enrichment analysis showed the downregulation of differentially expressed genes in chemotaxis. This study suggests that an applied EF is an effective cue to guiding OPC migration in neural regeneration and that transcriptional analysis contributes to the understanding of the mechanism of EF-guided cell migration. PMID- 26269461 TI - Introduction to the Symposium "Leading Students and Faculty to Quantitative Biology through Active Learning". AB - The broad aim of this symposium and set of associated papers is to motivate the use of inquiry-based, active-learning teaching techniques in undergraduate quantitative biology courses. Practical information, resources, and ready-to-use classroom exercises relevant to physicists, mathematicians, biologists, and engineers are presented. These resources can be used to address the lack of preparation of college students in STEM fields entering the workforce by providing experience working on interdisciplinary and multidisciplinary problems in mathematical biology in a group setting. Such approaches can also indirectly help attract and retain under-represented students who benefit the most from "non traditional" learning styles and strategies, including inquiry-based, collaborative, and active learning. PMID- 26269462 TI - Geophysiology of Wood Frogs: Landscape Patterns of Prevalence of Disease and Circulating Hormone Concentrations across the Eastern Range. AB - One of the major challenges for conservation physiologists is to determine how current or future environmental conditions relate to the health of animals at the population level. In this study, we measured prevalence of disease, mean condition of the body, and mean resting levels of corticosterone and testosterone in a total of 28 populations across the years 2011 and 2012, and correlated these measures of health to climatic suitability of habitat, using estimates from a model of the ecological niche of the wood frog's geographic range. Using the core periphery hypothesis as a theoretical framework, we predicted a higher prevalence and intensity of infection of Batrachochytrium dendrobatidis (Bd) and ranaviruses, two major amphibian pathogens causing disease, and higher resting levels of circulating corticosterone, an indicator of allostatic load incurred from living in marginal habitats. We found that Bd infections were rare (2% of individuals tested), while infections with ranavirus were much more common: ranavirus-infected individuals were found in 92% of ponds tested over the 2 years. Contrary to our predictions, rates of infection with ranaviruses were positively correlated with quality of the habitat with the highest prevalence at the core of the range, and plasma corticosterone concentrations measured when frogs were at rest were not correlated with quality of the habitat, the prevalence of ranavirus, or the intensity of infection. Prevalence and mean viral titers of ranavirus infection were higher in 2012 than in 2011, which coincided with lower levels of circulating corticosterone and testosterone and an extremely early time of breeding due to relatively higher temperatures during the winter. In addition, the odds of having a ranavirus infection increased with decreased body condition, and if animals had an infection, viral titers were positively correlated to levels of circulating testosterone concentration. By resolving these patterns, experiments can be designed to test hypotheses about the mechanisms that produce them, such as whether transmission of the ranavirus and tolerance of the host are greater or whether virulence is lower in populations within core habitats. While there is debate about which metrics serve as the best bioindicators of population health, the findings of this study demonstrate the importance of long-term monitoring of multiple physiological parameters to better understand the dynamic relationship between the environment and the health of wildlife populations over space and time. PMID- 26269463 TI - Publishers' charges for scoring systems may change clinical practice. PMID- 26269464 TI - Phase-dependent justification: the role of personal responsibility in fair healthcare. AB - The main aim of this paper is to examine the fairness of different ways of holding people responsible for healthcare-related choices. Our focus is on conceptualisations of responsibility that involve blame and sanctions, and our analytical approach is to provide a systematic discussion based on interrelated and successive health-related, lifestyle choices of an individual. We assess the already established risk-sharing, backward-looking and forward-looking views on responsibility according to a variety of standard objections. In conclusion, all of the proposed views on holding people responsible for their lifestyle choices are subjected to reasonable critiques, although the risk-sharing view fare considerably better than the others overall considered. With our analytical approach, we are able to identify how basic conditions for responsibility ascription alter along a time axis. Repeated relapses with respect to healthcare associated with persistent, unhealthy lifestyle choices, call for distinct attention. In such situations, contextualised reasoning and transparent policy making, rather than opaque clinical judgements, are required as steps towards fair allocation of healthcare resources. PMID- 26269465 TI - Adverse Health Effects of Benzene Exposure Among Children Following a Flaring Incident at the British Petroleum Refinery in Texas City. AB - This study examined the health effects of benzene exposure among children from a flaring incident at the British Petroleum (BP) refinery in Texas City, Texas. A total of 899 children (benzene exposed, n = 641 and unexposed, n = 258), aged <17 years, were included. Hematological analysis showed that white blood cell (*10(3)/uL) counts were significantly decreased in the exposed children compared with the unexposed children (7.1 +/- 2.2 versus 7.6 +/- 2.1, P = .001). Similarly, the hemoglobin (g/dL) levels were decreased significantly in the exposed group compared with the unexposed group (12.7 +/- 1.3 vs 13.1 +/- 1.5, P = .001). Conversely, platelet (*10(3)/uL) counts were increased significantly in the exposed group compared with the unexposed group (318.6 +/- 79.8 versus 266.9 +/- 58.8, P = .001). Hepatic enzymes were also significantly elevated among exposed children compared with the unexposed children. These findings suggest that children exposed to benzene are at a higher risk of developing both hepatic and bone marrow-related disorders. PMID- 26269466 TI - Combined Photothermal and Surface-Enhanced Raman Spectroscopy Effect from Spiky Noble Metal Nanoparticles Wrapped within Graphene-Polymer Layers: Using Layer-by layer Modified Reduced Graphene Oxide as Reactive Precursors. AB - To fabricate functionally integrated hybrid nanoparticles holds high importance in biomedical applications and is still a challenging task. In this study, we report the first reduced graphene oxide (rGO)-nobel metal hybrid particles that present simultaneously the photothermal and surface-enhanced Raman spectroscopy (SERS) effect from the inorganic part and drug loading, dispersibility, and controllability features from LbL polyelectrolyte multilayers. The hybrid particles where spiky noble metal particles were wrapped within rGO polyelectrolyte layers were prepared by a facile and controllable method. rGO template modified using polyethylenimine (PEI) and poly(acrylic acid) (PAA) via layer-by-layer technology served as the reactive precursors, and the morphologies of the particles could be facilely controlled via controlling the number of bilayers around the rGO template. The hybrid particle presented low cytotoxicity. After loading doxorubicin hydrochloride, the particles effectively induced cell death, and photothermal treatment further decreased cell viability. rGO-Ag hybrid particles could be prepared similarly. We expect the reported method provides an effective strategy to prepare rGO-noble metal hybrid nanoparticles that find potential biomedical applications. PMID- 26269467 TI - Microcirculatory dysfunction and resuscitation: why, when, and how. AB - Cardiovascular resuscitation is a cornerstone of critical care practice. Experimental advances have increased our understanding of the role of the microcirculation in shock states and the development of multi-organ failure. Strategies that target the microcirculation in such conditions, while theoretically appealing, have not yet been shown to impact upon clinical outcomes. This review outlines the current understanding of microcirculatory dysfunction in septic, cardiogenic, and hypovolaemic shock and outlines available treatments and strategies with reference to their effects upon the microcirculation. PMID- 26269468 TI - Non-invasive haemodynamic monitoring. A choice between trending and accuracy. PMID- 26269469 TI - Pitfalls of comparing incidences of awareness from NAP5 and from Brice studies. PMID- 26269470 TI - Practical details, confirmed safety and new targets. PMID- 26269471 TI - Reply from the authors. Anaesthetic management during open and percutaneous irreversible electroporation. PMID- 26269472 TI - Improved safety and efficacy of ultrasound-guided interscalene nerve block vs a nerve-stimulator guided technique. PMID- 26269473 TI - Reply from the authors. Safety benefit of ultrasound guidance. PMID- 26269474 TI - NAP5: aware of the limitations. PMID- 26269475 TI - Postoperative atrial fibrillation and diastolic dysfunction; the contribution of autonomic nervous system function. PMID- 26269476 TI - Does surgical technique add to the risk of bone cement implantation syndrome? PMID- 26269477 TI - Bone cement implantation syndrome affecting operating room personnel. PMID- 26269478 TI - Bone cement implantation syndrome--responses to queries. PMID- 26269479 TI - SDD and contextual effect. PMID- 26269480 TI - Reply from the authors. Reply: SDD and contextual effect. PMID- 26269487 TI - Insulation lifetime improvement of polyimide thin film neural implants. AB - OBJECTIVE: This work deals with studying and improving the insulation lifetime of polyimide-insulated thin film neural implants, or related polyimide-based medical implants. APPROACH: The evolution of the leak impedance of insulated conductors was investigated in saline water at 40 degrees C. The fabrication process as commonly found in literature for polyimide/platinum/polyimide microelectrode arrays was compared with three possible improvements: one based on lowering the curing temperature of the lower layer, one based on chemical activation and one based on an additional plasma activation step. MAIN RESULTS: The lower curing temperature process was found to yield a 7.5-fold improved lifetime compared with the state of the art process. Also, the leak impedances found after soak testing are an order of magnitude higher compared to the standard process. SIGNIFICANCE: By improving the lifetime and insulation impedance of polyimide insulation with one order of magnitude, this work increases the applicability of polyimide in chronic thin film neural implants considerably. PMID- 26269488 TI - Relationship between living alone and food and nutrient intake. AB - The increase in the number of individuals living alone has implications for nutrition and health outcomes. The aim of this review was to investigate whether there is a difference in food and nutrient intake between adults living alone and those living with others. Eight electronic databases were searched, using terms related to living alone, nutrition, food, and socioeconomic factors. Forty-one papers met the inclusion criteria, and data of interest were extracted. Results varied but suggested that, compared with persons who do not live alone, persons who live alone have a lower diversity of food intake, a lower consumption of some core foods groups (fruits, vegetables, and fish), and a higher likelihood of having an unhealthy dietary pattern. Associations between living alone and nutrient intake were unclear. Men living alone were more often observed to be at greater risk of undesirable intakes than women. The findings of this review suggest that living alone could negatively affect some aspects of food intake and contribute to the relationship between living alone and poor health outcomes, although associations could vary among socioeconomic groups. Further research is required to help to elucidate these findings. PMID- 26269489 TI - Health claims on food products in Southeast Asia: regulatory frameworks, barriers, and opportunities. AB - The Association of Southeast Asian Nations aims to act as a single market and allow free movement of goods, services, and manpower. The purpose of this article is to present an overview of the current regulatory framework for health claims in Southeast Asia and to highlight the current barriers and opportunities in the regulatory frameworks in the Association of Southeast Asian Nations. To date, 5 countries in Southeast Asia, i.e., Indonesia, Malaysia, the Philippines, Singapore, and Thailand, have regulations and guidelines to permit the use of health claims on food products. There are inconsistencies in the regulations and the types of evidence required for health claim applications in these countries. A clear understanding of the regulatory frameworks in these countries may help to increase trade in this fast-growing region and to provide direction for the food industry and the regulatory community to develop and market food products with better nutritional quality tailored to the needs of Southeast Asian consumers. PMID- 26269494 TI - Bone strength in children: understanding basic bone biomechanics. AB - The term 'bone strength' is often used to explain why some children's bones fracture while others do not. Bone strength describes the general integrity of bone; a complex organ with multiple structural levels and an array of biomechanical properties. Key biomechanical properties of bone include stiffness, toughness, ductility and mechanical strength. When measured in bone tissue, these properties are known as the intrinsic biomechanical properties of bone, while the extrinsic biomechanical properties reflect the structural behaviour of a whole bone. The fine balance between various and often opposing intrinsic and extrinsic biomechanical properties of bone is crucial for fracture resistance. When clinically evaluating a child with a fracture, an understanding of basic bone biomechanics helps determine the likely mechanism of injury and whether underlying reduced fracture resistance exists. PMID- 26269495 TI - Significance of the Glasgow Prognostic Score as a prognostic indicator for lung cancer surgery. AB - OBJECTIVES: The Glasgow Prognostic Score (GPS), which is calculated with C reactive protein (CRP) and albumin (Alb) values, is a prognostic indicator for various types of cancers. However, its role in lung cancer still remains unclear, and its optimal cut-off values are controversial. Here, we evaluated the significance of the GPS and adjusted GPS (a-GPS) using our institution's cut-off values in patients undergoing resection for primary lung cancer. METHODS: We analysed 1043 lung cancer patients who underwent resection between 1998 and 2012. The overall survival (OS) probabilities of the GPS subgroups were estimated using the Kaplan-Meier method and were compared using the log-rank test. The prognostic significance of the GPS and the a-GPS was assessed by the Cox proportional hazards model with clinicopathological variables and inflammation markers, such as the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR). The GPS was calculated based on cut-off values of 1.0 mg/dl for CRP and 3.5 g/dl for Alb, as previously reported. The a-GPS was calculated based on cut off values 0.3 mg/dl for CRP and 3.9 g/dl for Alb, which are the standard thresholds used by our institution. RESULTS: The GPS and the a-GPS were correlated with preoperative factors, such as age, sex, smoking status, the NLR and the PLR, and oncological factors, including the pathological stage, histological type and level of lymphovascular invasion. The 5-year OS rates were 82, 55 and 55% with GPS 0, 1 and 2 (1 vs 0: P < 0.01; 2 vs 1: P = 0.66), respectively, and 88, 67 and 59% with a-GPS 0, 1 and 2 (1 vs 0: P < 0.01; 2 vs 1: P = 0.04), respectively. Multivariable analysis revealed that the GPS [1 vs 0, hazard ratio (HR): 1.63, 2 vs 0, HR: 1.44] and the a-GPS (1 vs 0, HR: 2.00, 2 vs 0, HR: 2.10) were independent prognostic factors. The a-GPS classification showed a clearer prognostic distribution than the GPS classification. CONCLUSIONS: The GPS is a useful prognostic indicator of the OS in lung cancer surgery. The optimal cut-off values for GPS estimation may need to be re-evaluated. PMID- 26269493 TI - The Association Between Benzodiazepine Use and Depression Outcomes in Older Veterans. AB - Benzodiazepines (BZDs) are commonly prescribed to older adults with depression, but it is unknown whether they improve antidepressant (AD) adherence or depressive symptoms. We followed 297 older veterans diagnosed with depression and provided a new AD medication prospectively for 4 months. Data include validated self-report measures and VA pharmacy records. At initial assessment, 20.5% of participants were prescribed a BZD. Those with a BZD prescription at baseline were significantly more likely than those without to have a personality disorder, schizophrenia spectrum disorder, or other anxiety disorder, and higher depressive symptom and anxiety symptom scale scores on average. In adjusted regressions, BZD use was not significantly associated with AD adherence, any improvement in depressive symptoms, or a 50% reduction in depressive symptoms. Our results suggest BZD use concurrent with AD treatment does not significantly improve depressive outcomes in older veterans. PMID- 26269496 TI - A wireless transmission neural interface system for unconstrained non-human primates. AB - OBJECTIVE: Studying the brain in large animal models in a restrained laboratory rig severely limits our capacity to examine brain circuits in experimental and clinical applications. APPROACH: To overcome these limitations, we developed a high-fidelity 96-channel wireless system to record extracellular spikes and local field potentials from the neocortex. A removable, external case of the wireless device is attached to a titanium pedestal placed in the animal skull. Broadband neural signals are amplified, multiplexed, and continuously transmitted as TCP/IP data at a sustained rate of 24 Mbps. A Xilinx Spartan 6 FPGA assembles the digital signals into serial data frames for transmission at 20 kHz though an 802.11n wireless data link on a frequency-shift key-modulated signal at 5.7-5.8 GHz to a receiver up to 10 m away. The system is powered by two CR123A, 3 V batteries for 2 h of operation. MAIN RESULTS: We implanted a multi-electrode array in visual area V4 of one anesthetized monkey (Macaca fascicularis) and in the dorsolateral prefrontal cortex (dlPFC) of a freely moving monkey (Macaca mulatta). The implanted recording arrays were electrically stable and delivered broadband neural data over a year of testing. For the first time, we compared dlPFC neuronal responses to the same set of stimuli (food reward) in restrained and freely moving conditions. Although we did not find differences in neuronal responses as a function of reward type in the restrained and unrestrained conditions, there were significant differences in correlated activity. This demonstrates that measuring neural responses in freely moving animals can capture phenomena that are absent in the traditional head-fixed paradigm. SIGNIFICANCE: We implemented a wireless neural interface for multi-electrode recordings in freely moving non-human primates, which can potentially move systems neuroscience to a new direction by allowing one to record neural signals while animals interact with their environment. PMID- 26269498 TI - Childhood cancer--the role of birthweight and antenatal radiography. PMID- 26269497 TI - Interaction of long noncoding RNAs and microRNAs in the pathogenesis of idiopathic pulmonary fibrosis. AB - Long noncoding RNAs (lncRNAs) are transcribed RNAs with more than 200 nucleotides in length. A growing body of evidence supports the notion that lncRNAs act as competitive endogenous RNAs for microRNAs and play roles in physiological and pathological processes. Several studies have demonstrated the roles of microRNAs in the pathogenesis of idiopathic pulmonary fibrosis (IPF). However, it is unknown whether lncRNAs are involved in IPF. To investigate the roles of lncRNAs in IPF, we determined the interaction of lncRNAs and microRNAs by motif search and manual comparison. The sequences of the dysregulated microRNAs in IPF including miR-21, miR-31, miR-101, miR-29, miR-199, and let-7d were used to search NONCODE database containing 33,829 human lncRNAs. A total of 34 lncRNAs with potential binding sites to these microRNAs were identified. We then examined the expression levels of the identified lncRNAs in the lungs of IPF patients by real-time PCR. Of 34 lncRNAs, nine lncRNAs were dysregulated in the IPF lungs. Four of them were inversely correlated to the microRNA expression in IPF. Further studies revealed that silencing the lncRNA CD99 molecule pseudogene 1 (CD99P1) inhibited proliferation and alpha-smooth muscle actin expression of lung fibroblasts, while knockdown of the lncRNA n341773 increased collagen expression in lung fibroblasts. These results suggest that CD99P1 and n341773 may be involved in the regulation of lung fibroblast proliferation and differentiation. The identification of regulatory functions of lncRNAs in lung fibroblasts may provide new research directions for the therapy of IPF. PMID- 26269499 TI - Correction to 'The relative efficiency of modular and non-modular networks of different size'. PMID- 26269501 TI - Does kin selection moderate sexual conflict in Drosophila? AB - Two recent studies provide provocative experimental findings about the potential influence of kin recognition and cooperation on the level of sexual conflict in Drosophila melanogaster. In both studies, male fruit flies apparently curbed their mate-harming behaviours in the presence of a few familiar or related males, suggesting some form of cooperation mediated by kin selection. In one study, the reduction in agonistic behaviour by brothers apparently rendered them vulnerable to dramatic loss of paternity share when competing with an unrelated male. If these results are robust and generalizable, fruit flies could be a major new focus for the experimental study of kin selection and social evolution. In our opinion, however, the restrictive conditions required for male cooperation to be adaptive in this species make it unlikely to evolve. We investigated these phenomena in two different populations of D. melanogaster using protocols very similar to those in the two previous studies. Our experiments show no evidence for a reduction in mate harm based upon either relatedness or familiarity between males, and no reduction in male reproductive success when two brothers are in the presence of an unfamiliar, unrelated, 'foreign' male. Thus, the reduction of sexual conflict owing to male cooperation does not appear to be a general feature of the species, at least under domestication, and these contrasting results call for further investigation: in new populations, in the field and in the laboratory populations in which these phenomena have been reported. PMID- 26269500 TI - Breaking cover: neural responses to slow and fast camouflage-breaking motion. AB - Primates need to detect and recognize camouflaged animals in natural environments. Camouflage-breaking movements are often the only visual cue available to accomplish this. Specifically, sudden movements are often detected before full recognition of the camouflaged animal is made, suggesting that initial processing of motion precedes the recognition of motion-defined contours or shapes. What are the neuronal mechanisms underlying this initial processing of camouflaged motion in the primate visual brain? We investigated this question using intrinsic-signal optical imaging of macaque V1, V2 and V4, along with computer simulations of the neural population responses. We found that camouflaged motion at low speed was processed as a direction signal by both direction- and orientation-selective neurons, whereas at high-speed camouflaged motion was encoded as a motion-streak signal primarily by orientation-selective neurons. No population responses were found to be invariant to the camouflage contours. These results suggest that the initial processing of camouflaged motion at low and high speeds is encoded as direction and motion-streak signals in primate early visual cortices. These processes are consistent with a spatio temporal filter mechanism that provides for fast processing of motion signals, prior to full recognition of camouflage-breaking animals. PMID- 26269502 TI - Making pore choices: repeated regime shifts in stomatal ratio. AB - Ecologically important traits do not evolve without limits. Instead, evolution is constrained by the set of available and viable phenotypes. In particular, natural selection may only favour a narrow range of adaptive optima constrained within selective regimes. Here, I integrate data with theory to test whether selection explains phenotypic constraint. A global database of 599 plant species from 94 families shows that stomatal ratio, a trait affecting photosynthesis and defence against pathogens, is highly constrained. Most plants have their stomata on the lower leaf surface (hypostomy), but species with half their stomata on each surface (amphistomy) form a distinct mode in the trait distribution. A model based on a trade-off between maximizing photosynthesis and a fitness cost of upper stomata predicts a limited number of adaptive solutions, leading to a multimodal trait distribution. Phylogenetic comparisons show that amphistomy is the most common among fast-growing species, supporting the view that CO2 diffusion is under strong selection. These results indicate that selective optima stay within a relatively stable set of selective regimes over macroevolutionary time. PMID- 26269503 TI - Effects of Interference Between Selected Loci on the Mutation Load, Inbreeding Depression, and Heterosis. AB - A classical prediction from single-locus models is that inbreeding increases the efficiency of selection against partially recessive deleterious alleles (purging), thereby decreasing the mutation load and level of inbreeding depression. However, previous multilocus simulation studies found that increasing the rate of self-fertilization of individuals may not lead to purging and argued that selective interference among loci causes this effect. In this article, I derive simple analytical approximations for the mutation load and inbreeding depression, taking into account the effects of interference between pairs of loci. I consider two classical scenarios of nonrandomly mating populations: a single population undergoing partial selfing and a subdivided population with limited dispersal. In the first case, correlations in homozygosity between loci tend to reduce mean fitness and increase inbreeding depression. These effects are stronger when deleterious alleles are more recessive, but only weakly depend on the strength of selection against deleterious alleles and on recombination rates. In subdivided populations, interference increases inbreeding depression within demes, but decreases heterosis between demes. Comparisons with multilocus, individual-based simulations show that these analytical approximations are accurate as long as the effects of interference stay moderate, but fail for high deleterious mutation rates and low dominance coefficients of deleterious alleles. PMID- 26269504 TI - Genetic Control of Environmental Variation of Two Quantitative Traits of Drosophila melanogaster Revealed by Whole-Genome Sequencing. AB - Genetic studies usually focus on quantifying and understanding the existence of genetic control on expected phenotypic outcomes. However, there is compelling evidence suggesting the existence of genetic control at the level of environmental variability, with some genotypes exhibiting more stable and others more volatile performance. Understanding the mechanisms responsible for environmental variability not only informs medical questions but is relevant in evolution and in agricultural science. In this work fully sequenced inbred lines of Drosophila melanogaster were analyzed to study the nature of genetic control of environmental variance for two quantitative traits: starvation resistance (SR) and startle response (SL). The evidence for genetic control of environmental variance is compelling for both traits. Sequence information is incorporated in random regression models to study the underlying genetic signals, which are shown to be different in the two traits. Genomic variance in sexual dimorphism was found for SR but not for SL. Indeed, the proportion of variance captured by sequence information and the contribution to this variance from four chromosome segments differ between sexes in SR but not in SL. The number of studies of environmental variation, particularly in humans, is limited. The availability of full sequence information and modern computationally intensive statistical methods provides opportunities for rigorous analyses of environmental variability. PMID- 26269505 TI - Pregnancy Hyperglycemia in Prolactin Receptor Mutant, but Not Prolactin Mutant, Mice and Feeding-Responsive Regulation of Placental Lactogen Genes Implies Placental Control of Maternal Glucose Homeostasis. AB - Pregnancy is often viewed as a conflict between the fetus and mother over metabolic resources. Insulin resistance occurs in mothers during pregnancy but does not normally lead to diabetes because of an increase in the number of the mother's pancreatic beta cells. In mice, this increase is dependent on prolactin (Prl) receptor signaling but the source of the ligand has been unclear. Pituitary derived Prl is produced during the first half of pregnancy in mice but the placenta produces Prl-like hormones from implantation to term. Twenty-two separate mouse genes encode the placenta Prl-related hormones, making it challenging to assess their roles in knockout models. However, because at least four of them are thought to signal through the Prl receptor, we analyzed Prlr mutant mice and compared their phenotypes with those of Prl mutants. We found that whereas Prlr mutants develop hyperglycemia during gestation, Prl mutants do not. Serum metabolome analysis showed that Prlr mutants showed other changes consistent with diabetes. Despite the metabolic changes, fetal growth was normal in Prlr mutants. Of the four placenta-specific, Prl-related hormones that have been shown to interact with the Prlr, their gene expression localizes to different endocrine cell types. The Prl3d1 gene is expressed by trophoblast giant cells both in the labyrinth layer, sitting on the arterial side where maternal blood is highest in oxygen and nutrients, and in the junctional zone as maternal blood leaves the placenta. Expression increases during the night, though the increase in the labyrinth is circadian whereas it occurs only after feeding in the junctional zone. These data suggest that the placenta has a sophisticated endocrine system that regulates maternal glucose metabolism during pregnancy. PMID- 26269507 TI - Synpolydactyly of the hand: a radiographic classification. AB - Synpolydactyly is an uncommon congenital anomaly characterized by polydactyly with syndactyly in the central hand. The purpose of this investigation was to develop and assess the reliability of a radiographic classification system for synpolydactyly. We identified 56 hands with central synpolydactyly and developed a radiographic classification system that categorizes by the location within the hand, the bony level of polydactyly, and the presence of a delta phalanx. Four paediatric hand surgeons independently reviewed each radiograph to establish reliability. There was exact agreement among raters in 40 cases (71%). The inter rater reliability was 0.97 and intra-rater reliability was at least 0.87. Seven of 16 bilateral cases had symmetric deformity classification. The most common presentations were types 1A and 2A. We present a new, reliable radiographic classification system for synpolydactyly that will allow improved communication between clinicians and serve as a foundation for future investigations. LEVEL OF EVIDENCE: 2. PMID- 26269508 TI - A single injection of collagenase clostridium histolyticum for the treatment of moderate Dupuytren's contracture: a 2 year follow-up of 47 patients. PMID- 26269509 TI - A functional test in assessment of hand dexterity in young children. PMID- 26269506 TI - Steroidogenic factor 1 differentially regulates fetal and adult leydig cell development in male mice. AB - The nuclear receptor steroidogenic factor 1 (SF-1, AD4BP, NR5A1) is a key regulator of the endocrine axes and is essential for adrenal and gonad development. Partial rescue of Nr5a1(-/-) mice with an SF-1-expressing transgene caused a hypomorphic phenotype that revealed its roles in Leydig cell development. In contrast to controls, all male rescue mice (Nr5a1(-/-);tg(+/0)) showed varying signs of androgen deficiency, including spermatogenic arrest, cryptorchidism, and poor virilization. Expression of various Leydig cell markers measured by immunohistochemistry, Western blot analysis, and RT-PCR indicated fetal and adult Leydig cell development were differentially impaired. Whereas fetal Leydig cell development was delayed in Nr5a1(-/-);tg(+/0) embryos, it recovered to control levels by birth. In contrast, Sult1e1, Vcam1, and Hsd3b6 transcript levels in adult rescue testes indicated complete blockage in adult Leydig cell development. In addition, between Postnatal Days 8 and 12, peritubular cells expressing PTCH1, SF-1, and CYP11A1 were observed in control testes but not in rescue testes, indicating SF-1 is needed for either survival or differentiation of adult Leydig cell progenitors. Cultured prepubertal rat peritubular cells also expressed SF-1 and PTCH1, but Cyp11a1 was expressed only after treatment with cAMP and retinoic acid. Together, data show SF-1 is needed for proper development of fetal and adult Leydig cells but with distinct primary functions; in fetal Leydig cells, it regulates differentiation, whereas in adult Leydig cells it regulates progenitor cell formation and/or survival. PMID- 26269510 TI - The EuroSCORE II performances in the Spanish cardiac surgical population. PMID- 26269511 TI - Re: Repair of complicated type B dissection with an isolated left vertebral artery using the stented elephant trunk technique. PMID- 26269512 TI - Reply to Nezic. PMID- 26269516 TI - ISQua founders' reunion, Udine, June 2015. PMID- 26269515 TI - Real-Time Imaging Reveals Local, Transient Vascular Permeability, and Tumor Cell Intravasation Stimulated by TIE2hi Macrophage-Derived VEGFA. AB - Dissemination of tumor cells is an essential step in metastasis. Direct contact between a macrophage, mammalian-enabled (MENA)-overexpressing tumor cell, and endothelial cell [Tumor MicroEnvironment of Metastasis (TMEM)] correlates with metastasis in breast cancer patients. Here we show, using intravital high resolution two-photon microscopy, that transient vascular permeability and tumor cell intravasation occur simultaneously and exclusively at TMEM. The hyperpermeable nature of tumor vasculature is described as spatially and temporally heterogeneous. Using real-time imaging, we observed that vascular permeability is transient, restricted to the TMEM, and required for tumor cell dissemination. VEGFA signaling from TIE2(hi) TMEM macrophages causes local loss of vascular junctions, transient vascular permeability, and tumor cell intravasation, demonstrating a role for the TMEM within the primary mammary tumor. These data provide insight into the mechanism of tumor cell intravasation and vascular permeability in breast cancer, explaining the value of TMEM density as a predictor of distant metastatic recurrence in patients. SIGNIFICANCE: Tumor vasculature is abnormal with increased permeability. Here, we show that VEGFA signaling from TIE2(hi) TMEM macrophages results in local, transient vascular permeability and tumor cell intravasation. These data provide evidence for the mechanism underlying the association of TMEM with distant metastatic recurrence, offering a rationale for therapies targeting TMEM. PMID- 26269517 TI - Development and validation of patient-reported outcomes scale for hypertension. AB - OBJECTIVE: To validate a patient-reported outcomes (PROs) measure for patients with hypertension. DESIGN: This was a validation study that employed mixed methods including classical test theory, item response theory, and reliability and validity evaluation. SETTING: The community health centers in two Chinese cities. PARTICIPANTS: Fifteen patients participated in the pilot survey, and 641 patients completed the PRO survey. MAIN OUTCOME MEASURES: Classical test theory and item response theory were applied to the item selection. Evaluations and adjustments were based on results of reliability, validity, responsiveness and feasibility analyses. RESULTS: The item selection process produced a final scale with 4 domains (physiology, psychology, society and treatment), 12 subdomains and 56 items. According to confirmatory factor analysis, the construct validity was adequate. The split-half reliability, Cronbach's alpha coefficients and responsiveness both in each subdomain and in the whole scale were also acceptable, as was feasibility. CONCLUSIONS: Mixed methods were beneficial for developing this scale and could be applied to PROs in other health areas. The instrument provides a means for comprehensive assessment of the impact of hypertension, and for quantification of benefits of hypertension interventions from the patients' perspective. PMID- 26269518 TI - Evaluation of radiation doses in patient and medical staff during endoscopic retrograde cholangiopancreatography procedures. AB - The radiation exposure dose must be optimised because the hazard resulting from an interventional radiology procedure is long term depending on the patient. The aim of this study was to measure the radiation doses received by the patients and medical staff during endoscopic retrograde cholangiopancreatography (ERCP) procedures. Data were collected during 126 ERCP procedures, including the dose area product (DAP), entrance dose (ED), effective dose (E), fluoroscopy time (T) and number of digital radiographs (F). The medical staff members each wore a personal thermoluminescence dosemeter to monitor exposure during ERCP procedures. The mean DAP, ED, E and T were 47.06 Gy cm(2), 196.06 mGy, 8.93 mSv, 7.65 min and 9.21 images, respectively. The mean dose to the staff was 0.175 mSv and that to the assistant was 0.069 mSv. The dose to the medical staff was minimal when appropriate protective measures were used. The large variation in the patient doses must be further investigated. PMID- 26269520 TI - Influence of menopause and Type 2 diabetes on pulmonary oxygen uptake kinetics and peak exercise performance during cycling. AB - We investigated if the magnitude of the Type 2 diabetes (T2D)-induced impairments in peak oxygen uptake (VO2) and VO2 kinetics was affected by menopausal status. Twenty-two women with T2D (8 premenopausal, 14 postmenopausal), and 22 nondiabetic (ND) women (11 premenopausal, 11 postmenopausal) matched by age (range = 30-59 yr) were recruited. Participants completed four bouts of constant load cycling at 80% of their ventilatory threshold for the determination of VO2 kinetics. Cardiac output (CO) (inert gas rebreathing) was recorded at rest and at 30 s and 240 s during two additional bouts. Peak VO2 was significantly (P < 0.05) reduced in both groups with T2D compared with ND counterparts (premenopausal, 1.79 +/- 0.16 vs. 1.55 +/- 0.32 l/min; postmenopausal, 1.60 +/- 0.30 vs. 1.45 +/- 0.24 l/min). The time constant of phase II of the VO2 response was slowed (P < 0.05) in both groups with T2D compared with healthy counterparts (premenopausal, 29.1 +/- 11.2 vs. 43.0 +/- 12.2 s; postmenopausal, 33.0 +/- 9.1 vs. 41.8 +/- 17.7 s). At rest and during submaximal exercise absolute CO responses were lower, but the "gains" in CO larger (both P < 0.05) in both groups with T2D. Our results suggest that the magnitude of T2D-induced impairments in peak VO2 and VO2 kinetics is not affected by menopausal status in participants younger than 60 yr of age. PMID- 26269519 TI - Shear stress blunts tubuloglomerular feedback partially mediated by primary cilia and nitric oxide at the macula densa. AB - The present study tested whether primary cilia on macula densa serve as a flow sensor to enhance nitric oxide synthase 1 (NOS1) activity and inhibit tubuloglomerular feedback (TGF). Isolated perfused macula densa was loaded with calcein red and 4,5-diaminofluorescein diacetate to monitor cell volume and nitric oxide (NO) generation. An increase in tubular flow rate from 0 to 40 nl/min enhanced NO production by 40.0 +/- 1.2%. The flow-induced NO generation was blocked by an inhibitor of NOS1 but not by inhibition of the Na/K/2Cl cotransporter or the removal of electrolytes from the perfusate. NO generation increased from 174.8 +/- 21 to 276.1 +/- 24 units/min in cultured MMDD1 cells when shear stress was increased from 0.5 to 5.0 dynes/cm(2). The shear stress induced NO generation was abolished in MMDD1 cells in which the cilia were disrupted using a siRNA to ift88. Increasing the NaCl concentration of the tubular perfusate from 10 to 80 mM NaCl in the isolated perfused juxtaglomerular preparation reduced the diameter of the afferent arteriole by 3.8 +/- 0.1 MUm. This response was significantly blunted to 2.5 +/- 0.2 MUm when dextran was added to the perfusate to increase the viscosity and shear stress. Inhibition of NOS1 blocked the effect of dextran on TGF response. In vitro, the effects of raising perfusate viscosity with dextran on tubular hydraulic pressure were minimized by reducing the outflow resistance to avoid stretching of tubular cells. These results suggest that shear stress stimulates primary cilia on the macula densa to enhance NO generation and inhibit TGF responsiveness. PMID- 26269522 TI - Chronic selective serotonin reuptake inhibition modulates endothelial dysfunction and oxidative state in rat chronic mild stress model of depression. AB - Major depression is known to be associated with cardiovascular abnormalities, and oxidative stress has been suggested to play a role. We tested the hypothesis that antidepressant treatment reduces oxidative stress and endothelial dysfunctions in the chronic mild stress (CMS) model of depression in rats. Rats with >30% reduction in sucrose intake after 4 wk of CMS were defined in the study as CMS susceptible and compared with unstressed controls. Sixteen CMS-susceptible and eight unstressed rats were treated during weeks 5 to 8 of the CMS protocol with escitalopram. Escitalopram-treated rats with >20% recovery in the sucrose consumption during the last 2 wk of treatment were defined as escitalopram responders. Rats that did not reach these criteria were defined as escitalopram nonresponders. In the open field test, escitalopram responders demonstrated anxiolytic effect of treatment. In mesenteric small arteries, escitalopram affected neither NO nor cyclooxygenase-1 (COX-1)-mediated vasodilation. Escitalopram potentiated endothelium-dependent hyperpolarization-like response, which was suppressed in the vehicle-treated CMS-susceptible rats and reduced COX 2-dependent relaxation, which was elevated in the vehicle-treated CMS-susceptible rats. Escitalopram did not affect blood pressure and heart rate, which were elevated in the vehicle-treated CMS-susceptible rats. Oxidative stress markers were changed in association with CMS in liver, heart, and brain. Escitalopram normalized oxidative stress markers in the majority of tissues. This study demonstrates that the antidepressant effect of escitalopram is associated with partial improvement of endothelial function in small arteries affecting COX-2 and endothelium-dependent hyperpolarization-like pathways. PMID- 26269521 TI - Aberrant REDD1-mTORC1 responses to insulin in skeletal muscle from Type 2 diabetics. AB - The objective of this study was to establish whether alterations in the REDD1 mTOR axis underlie skeletal muscle insensitivity to insulin in Type 2 diabetic (T2D), obese individuals. Vastus lateralis muscle biopsies were obtained from lean, control and obese, T2D subjects under basal and after a 2-h hyperinsulinemic (40 mU.m(-2).min(-1))-euglycemic (5 mM) clamp. Muscle lysates were examined for total REDD1, and phosphorylated Akt, S6 kinase 1 (S6K1), 4E BP1, ERK1/2, and MEK1/2 via Western blot analysis. Under basal conditions [(-) insulin], T2D muscle exhibited higher S6K1 and ERK1/2 and lower 4E-BP1 phosphorylation (P < 0.05), as well as elevations in blood cortisol, glucose, insulin, glycosylated hemoglobin (P < 0.05) vs. lean controls. Following insulin infusion, whole body glucose disposal rates (GDR; mg/kg/min) were lower (P < 0.05) in the T2D vs. the control group. The basal-to-insulin percent change in REDD1 expression was higher (P < 0.05) in muscle from the T2D vs. the control group. Whereas, the basal-to-insulin percent change in muscle Akt, S6K1, ERK1/2, and MEK1/2 phosphorylation was significantly lower (P < 0.05) in the T2D vs. the control group. Findings from this study propose a REDD1-regulated mechanism in T2D skeletal muscle that may contribute to whole body insulin resistance and may be a target to improve insulin action in insulin-resistant individuals. PMID- 26269523 TI - IL-15Ralpha is a determinant of muscle fuel utilization, and its loss protects against obesity. AB - IL-15Ralpha is the widely expressed primary binding partner for IL-15. Because of the wide distribution in nonlymphoid tissues like skeletal muscle, adipose, or liver, IL-15/IL-15Ralpha take part in physiological and metabolic processes not directly related to immunity. In fast muscle, lack of IL-15Ralpha promotes an oxidative switch, with increased mitochondrial biogenesis and fatigue resistance. These effects are predicted to reproduce some of the benefits of exercise and, therefore, improve energy homeostasis. However, the direct effects of IL-15Ralpha on metabolism and obesity are currently unknown. We report that mice lacking IL 15Ralpha (IL-15Ralpha(-/-)) are resistant to diet-induced obesity (DIO). High-fat diet-fed IL-15Ralpha(-/-) mice have less body and liver fat accumulation than controls. The leaner phenotype is associated with increased energy expenditure and enhanced fatty acid oxidation by muscle mitochondria. Despite being protected against DIO, IL-15Ralpha(-/-) are hyperglycemic and insulin-resistant. These findings identify novel roles for IL-15Ralpha in metabolism and obesity. PMID- 26269525 TI - mTOR in Brain Physiology and Pathologies. AB - TOR (target of rapamycin) and its mammalian ortholog mTOR have been discovered in an effort to understand the mechanisms of action of the immunosuppressant drug rapamycin extracted from a bacterium of the Easter Island (Rapa Nui) soil. mTOR is a serine/threonine kinase found in two functionally distinct complexes, mTORC1 and mTORC2, which are differentially regulated by a great number of nutrients such as glucose and amino acids, energy (oxygen and ATP/AMP content), growth factors, hormones, and neurotransmitters. mTOR controls many basic cellular functions such as protein synthesis, energy metabolism, cell size, lipid metabolism, autophagy, mitochondria, and lysosome biogenesis. In addition, mTOR controlled signaling pathways regulate many integrated physiological functions of the nervous system including neuronal development, synaptic plasticity, memory storage, and cognition. Thus it is not surprising that deregulation of mTOR signaling is associated with many neurological and psychiatric disorders. Preclinical and preliminary clinical studies indicate that inhibition of mTORC1 can be beneficial for some pathological conditions such as epilepsy, cognitive impairment, and brain tumors, whereas stimulation of mTORC1 (direct or indirect) can be beneficial for other pathologies such as depression or axonal growth and regeneration. PMID- 26269527 TI - The tumor suppressor FBW7 controls ciliary length. PMID- 26269528 TI - Tumoral Immune Resistance Mediated by Enzymes That Degrade Tryptophan. AB - Cancer patients mount T-lymphocyte responses against antigens expressed selectively by their malignancy, but these responses often fail to control their disease, because tumors select mechanisms that allow them to resist immune destruction. Among the numerous resistance mechanisms that have been proposed, metabolic inhibition of T cells by tryptophan catabolism deserves particular attention, because of the frequent expression of tryptophan-degrading enzymes in human tumors, and because in vitro and in vivo studies have shown that their enzymatic activity can be readily blocked by pharmacologic inhibitors, thereby restoring T-cell-mediated tumor cell killing and paving the way to targeted therapeutic intervention. In view of recent observations, and taking into account the differences between human and mouse data that differ in several aspects, in this Cancer Immunology at the Crossroads article, we discuss the role of the three enzymes that have been proposed to control tryptophan catabolism in tumoral immune resistance: indoleamine 2,3-dioxygenase 1 (IDO1), tryptophan 2,3 dioxygenase (TDO), and indoleamine 2,3-dioxygenase 2 (IDO2). PMID- 26269526 TI - Cardiac Regeneration and Stem Cells. AB - After decades of believing the heart loses the ability to regenerate soon after birth, numerous studies are now reporting that the adult heart may indeed be capable of regeneration, although the magnitude of new cardiac myocyte formation varies greatly. While this debate has energized the field of cardiac regeneration and led to a dramatic increase in our understanding of cardiac growth and repair, it has left much confusion in the field as to the prospects of regenerating the heart. Studies applying modern techniques of genetic lineage tracing and carbon 14 dating have begun to establish limits on the amount of endogenous regeneration after cardiac injury, but the underlying cellular mechanisms of this regeneration remained unclear. These same studies have also revealed an astonishing capacity for cardiac repair early in life that is largely lost with adult differentiation and maturation. Regardless, this renewed focus on cardiac regeneration as a therapeutic goal holds great promise as a novel strategy to address the leading cause of death in the developed world. PMID- 26269530 TI - The 2015 Garrod Lecture: Why is improvement difficult? AB - The pressing need to measure and improve antibiotic use was recognized >40 years ago, so why have we failed to achieve sustained improvement at scale? In his 2014 Reith Lectures about the future of medicine, the US surgeon Atul Gawande said that failure in medicine is largely due to ineptitude (failure to use existing knowledge) rather than ignorance (lack of knowledge). Consequently, it is notable that most interventions to improve antimicrobial prescribing are either designed to educate individual practitioners or patients about policies or to restrict prescribing to make practitioners follow policies. Interventions that enable practitioners to apply existing knowledge through decision support, feedback and action planning are relatively uncommon. There is an urgent need to improve the design and reporting of interventions to change behaviour. However, achieving sustained improvement at scale will also require a more profound understanding of the role of context. What makes contexts receptive to change and which elements of context, under what circumstances, are important for human performance? Answering these questions will require interdisciplinary work with social scientists to integrate complementary approaches from human factors and ergonomics, improvement science and educational research. We need to rethink professional education to embrace complexity and enable teams to learn in practice. Workplace-based learning of improvement science will enable students and early-career professionals to become change agents and transform training from a burden on clinical teams into a driver for improvement. This will make better use of existing resources, which is the key to sustainability at scale. PMID- 26269529 TI - Pain typology and incident endometriosis. AB - STUDY QUESTION: What are the pain characteristics among women, with no prior endometriosis diagnosis, undergoing laparoscopy or laparotomy regardless of clinical indication? SUMMARY ANSWER: Women with surgically visualized endometriosis reported the highest chronic/cyclic pain and significantly greater dyspareunia, dysmenorrhea, and dyschezia compared with women with other gynecologic pathology (including uterine fibroids, pelvic adhesions, benign ovarian cysts, neoplasms and congenital Mullerian anomalies) or a normal pelvis. WHAT IS KNOWN ALREADY: Prior research has shown that various treatments for pain associated with endometriosis can be effective, making identification of specific pain characteristics in relation to endometriosis necessary for informing disease diagnosis and management. STUDY DESIGN, SIZE, DURATION: The study population for these analyses includes the ENDO Study (2007-2009) operative cohort: 473 women, ages 18-44 years, who underwent a diagnostic and/or therapeutic laparoscopy or laparotomy at one of 14 surgical centers located in Salt Lake City, UT or San Francisco, CA. Women with a history of surgically confirmed endometriosis were excluded. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Endometriosis was defined as surgically visualized disease; staging was based on revised American Society for Reproductive Medicine (rASRM) criteria. All women completed a computer assisted personal interview at baseline specifying 17 types of pain (rating severity via 11-point visual analog scale) and identifying any of 35 perineal and 60 full-body front and 60 full-body back sites for which they experienced pain in the last 6 months. MAIN RESULTS AND THE ROLE OF CHANCE: There was a high prevalence (>=30%) of chronic and cyclic pelvic pain reported by the entire study cohort regardless of post-operative diagnosis. However, women with a post operative endometriosis diagnosis, compared with women diagnosed with other gynecologic disorders or a normal pelvis, reported more cyclic pelvic pain (49.5% versus 31.0% and 33.1%, P < 0.001). Additionally, women with endometriosis compared with women with a normal pelvis experienced more chronic pain (44.2 versus 30.2%, P = 0.04). Deep pain with intercourse, cramping with periods, and pain with bowel elimination were much more likely reported in women with versus without endometriosis (all P < 0.002). A higher percentage of women diagnosed with endometriosis compared with women with a normal pelvis reported vaginal (22.6 versus 10.3%, P < 0.01), right labial (18.4 versus 8.1%, P < 0.05) and left labial pain (15.3 versus 3.7%, P < 0.01) along with pain in the right/left hypogastric and umbilical abdominopelvic regions (P < 0.05 for all). Among women with endometriosis, no clear and consistent patterns emerged regarding pain characteristics and endometriosis staging or anatomic location. LIMITATIONS, REASONS FOR CAUTION: Interpretation of our findings requires caution given that we were limited in our assessment of pain characteristics by endometriosis staging and anatomic location due to the majority of women having minimal (stage I) disease (56%) and lesions in peritoneum-only location (51%). Significance tests for pain topology related to gynecologic pathology were not corrected for multiple comparisons. WIDER IMPLICATIONS OF THE FINDINGS: Results of our research suggest that while women with endometriosis appear to have higher pelvic pain, particularly dyspareunia, dysmenorrhea, dyschezia and pain in the vaginal and abdominopelvic area than women with other gynecologic disorders or a normal pelvis, pelvic pain is commonly reported among women undergoing laparoscopy, even among women with no identified gynecologic pathology. Future research should explore causes of pelvic pain among women who seek out gynecologic care but with no apparent gynecologic pathology. Given our and other's research showing little correlation between pelvic pain and rASRM staging among women with endometriosis, further development and use of a classification system that can better predict outcomes for endometriosis patients with pelvic pain for both surgical and nonsurgical treatment is needed. STUDY FUNDING/COMPETING INTERESTS: Supported by the Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts NO1-DK-6-3428, NO1-DK-6-3427, and 10001406-02). The authors have no potential competing interests. PMID- 26269532 TI - Postural and diurnal fluctuations in intraocular pressure across the spectrum of glaucoma. AB - AIMS: To evaluate postural fluctuations (PFs) and diurnal variation (DV) of intraocular pressure (IOP) in patients with untreated glaucoma, glaucoma suspects and healthy volunteers, and study their relationship, if any, to the extent of glaucomatous damage. METHODS: This prospective, observational cross-sectional study was carried out in a tertiary care referral institution. The patient population included five groups of patients comprising the following: 19 with ocular hypertension (OHT), 26 with optic discs suspicious for glaucoma (DS), 18 with normal tension glaucoma (NTG), 19 with primary open angle glaucoma (POAG) and 20 normal subjects. The IOP was measured at four time periods using Perkins tonometer, in sitting and supine positions. The main outcome measures were change in IOP with posture, the DV in both postures and the relationship between PF, DV and the extent of visual field damage. RESULTS: The supine IOP was significantly higher than the sitting IOP, at all time points of the day, in all groups (p<0.001). The PF at 04:30 was significantly higher in POAG, OHT and NTG. The PF at 09:00 correlated significantly with the mean deviation (MD) on visual fields in the NTG group (r=0.735; p=0.001). The DV did not correlate with the MD in any of the five groups studied. CONCLUSIONS: The significantly higher supine IOP is frequently missed in routine glaucoma practice. An early morning supine IOP measurement may reveal a peak IOP hitherto not picked up during routine office IOP measurements, and may be a useful measurement in unexplained progressive glaucoma. PMID- 26269531 TI - Perivascular M2 Macrophages Stimulate Tumor Relapse after Chemotherapy. AB - Tumor relapse after chemotherapy-induced regression is a major clinical problem, because it often involves inoperable metastatic disease. Tumor-associated macrophages (TAM) are known to limit the cytotoxic effects of chemotherapy in preclinical models of cancer. Here, we report that an alternatively activated (M2) subpopulation of TAMs (MRC1(+)TIE2(Hi)CXCR4(Hi)) accumulate around blood vessels in tumors after chemotherapy, where they promote tumor revascularization and relapse, in part, via VEGF-A release. A similar perivascular, M2-related TAM subset was present in human breast carcinomas and bone metastases after chemotherapy. Although a small proportion of M2 TAMs were also present in hypoxic tumor areas, when we genetically ablated their ability to respond to hypoxia via hypoxia-inducible factors 1 and 2, tumor relapse was unaffected. TAMs were the predominant cells expressing immunoreactive CXCR4 in chemotherapy-treated mouse tumors, with the highest levels expressed by MRC1(+) TAMs clustering around the tumor vasculature. Furthermore, the primary CXCR4 ligand, CXCL12, was upregulated in these perivascular sites after chemotherapy, where it was selectively chemotactic for MRC1(+) TAMs. Interestingly, HMOX-1, a marker of oxidative stress, was also upregulated in perivascular areas after chemotherapy. This enzyme generates carbon monoxide from the breakdown of heme, a gas known to upregulate CXCL12. Finally, pharmacologic blockade of CXCR4 selectively reduced M2-related TAMs after chemotherapy, especially those in direct contact with blood vessels, thereby reducing tumor revascularization and regrowth. Our studies rationalize a strategy to leverage chemotherapeutic efficacy by selectively targeting this perivascular, relapse-promoting M2-related TAM cell population. PMID- 26269533 TI - The influence of needle gauge and infection source on vitreous aspirate cultures. AB - BACKGROUND/AIMS: While the Endophthalmitis Vitrectomy Study (EVS) included only post-cataract surgery patients, the methods and data from that study are widely applied in the management of endophthalmitis of all types. We sought to examine how our experience with in-office vitreous aspiration differed from the EVS in two ways: first, by reviewing microbiological culture yields from vitreous aspirates obtained using 30-gauge needles versus 25-27-gauge needles and second, by reviewing culture yields in cases of endogenous versus non-endogenous endophthalmitis. METHODS: Cases of endophthalmitis over a 14-year period were reviewed when vitreous tap was the initial diagnostic procedure. The data included infection source, needle size used to obtain a vitreous aspirate, organism cultured and rates of unsuccessful attempts at vitreous aspiration or dry taps. RESULTS: 10 cases were endogenous endophthalmitis, while 36 cases were a mix of postoperative, post-traumatic, post-intravitreal injection and miscellaneous patients. A positive microbiological culture was obtained in 11/36 (31%) of vitreous taps using a 25-27-gauge needle and in 8/10 (80%) taps using a 30-gauge needle (p<0.01). A positive vitreous culture was obtained in 18/36 (50%) of all non-endogenous cases, while a positive result was obtained in 0/10 (0%) cases of endogenous endophthalmitis (p<0.01). CONCLUSIONS: The use of a smaller needle in obtaining vitreous samples in endophthalmitis did not lower the microbiological yield. A positive microbiological yield was significantly less likely in cases of endogenous endophthalmitis compared with non-endogenous cases. Vitreous tap as a method for identifying the causative organism in endogenous endophthalmitis was of limited utility. PMID- 26269534 TI - Anatomic and visual function outcomes in paediatric idiopathic intracranial hypertension. AB - BACKGROUND: There is a paucity of literature describing risk factors for vision loss in paediatric idiopathic intracranial hypertension (IIH). We investigate the final visual function, spectral domain optical coherence tomography (SD-OCT) and enhanced depth imaging (EDI)-OCT findings in children with papilledema caused by IIH. METHODS: Medical records of 31 patients with paediatric IIH (age <=17 years) were retrospectively reviewed. Optic disc photographs on presentation and automated perimetry, SD-OCT and EDI-OCT imaging on final follow-up visit were statistically analysed to identify patient characteristics and anatomic findings associated with irreversible vision loss. RESULTS: Permanent visual acuity or visual field loss developed in 19% of study eyes. Papilledema of modified Frisen grade >=3 on presentation was highly predictive of permanent vision loss (p<0.001), while associations between pubertal status and visual function outcome failed to reach statistical significance. SD-OCT revealed optic atrophy in 13% and photoreceptor loss in 19% of eyes, with both findings highly associated with vision loss (p<0.0001). Optic disc drusen was noted in 48% of study eyes by EDI OCT but was not found to be predictive of visual outcome. CONCLUSIONS: Clinical observation of high papilledema grade on presentation is predictive of poor visual outcomes. Vision loss is associated not only with optic atrophy but also with photoreceptor damage. Interestingly, a high proportion of study eyes had optic disc drusen, which was not associated with vision loss, but can be a diagnostic challenge in distinguishing true papilledema from pseudopapilledema. PMID- 26269535 TI - Influence of disc-fovea angle and retinal blood vessels on interindividual variability of circumpapillary retinal nerve fibre layer. AB - BACKGROUND: To assess whether intersubject variability of circumpapillary retinal nerve fibre layer (RNFL) thickness in healthy subjects acquired with spectral domain optical coherence tomography (SD-OCT) can be reduced by considering the disc-fovea angle (DFA), either alone or together with a compensation based on retinal blood vessel distribution (RVD). METHODS: 106 healthy volunteers underwent SD-OCT examination centred on the optic disc (OD) and on the macula. OD contours and foveal positions were automatically calculated. RVD at 3.4 mm diameter circle was manually assessed. We made two approaches to reduce interindividual variability in RNFL values using compensation processes; RVD compensation: RNFL thickness values were compensated according to RVD variation (RNFLRVD) and DFA compensation: we shifted the RNFL thickness measurements according to the DFA (RNFLDFA). Coefficient of variance (CoV) was calculated in 12 clock hour sectors for original RNFL (RNFLo), RNFLDFA, RNFLRVD and RNFL with both compensation methods (RNFLDFA-RVD). RESULTS: Compared with the mean CoV of RNFLO, mean CoV of RNFLDFA, RNFLRVD and RNFLDFA-RVD was changed by -0.71% (p>0.05), -9.51% (p<0.001) and -7.55% (p=0.001), respectively. When compared with RNFLDFA, RNFL DFA-RVD significantly reduced the mean CoV by -6.69% (p=0.001), while compared with RNFLRVD, RNFL DFA-RVD did not significantly increase the mean CoV (+2.20%), (p>0.05). CONCLUSIONS: Although reaching an improvement in some sectors, rotation of RNFL measurements according to the DFA on average does not reduce intersubject variability of RNFL. However, adjusting for RVD reduced the variance significantly. The results reinforce our work in assessing RVD as an important anatomical factor responsible for intersubject variability in RNFL measurements. PMID- 26269524 TI - The Mitochondrial Permeability Transition Pore: Channel Formation by F-ATP Synthase, Integration in Signal Transduction, and Role in Pathophysiology. AB - The mitochondrial permeability transition (PT) is a permeability increase of the inner mitochondrial membrane mediated by a channel, the permeability transition pore (PTP). After a brief historical introduction, we cover the key regulatory features of the PTP and provide a critical assessment of putative protein components that have been tested by genetic analysis. The discovery that under conditions of oxidative stress the F-ATP synthases of mammals, yeast, and Drosophila can be turned into Ca(2+)-dependent channels, whose electrophysiological properties match those of the corresponding PTPs, opens new perspectives to the field. We discuss structural and functional features of F-ATP synthases that may provide clues to its transition from an energy-conserving into an energy-dissipating device as well as recent advances on signal transduction to the PTP and on its role in cellular pathophysiology. PMID- 26269536 TI - Assessing the readability of ClinicalTrials.gov. AB - OBJECTIVE: ClinicalTrials.gov serves critical functions of disseminating trial information to the public and helping the trials recruit participants. This study assessed the readability of trial descriptions at ClinicalTrials.gov using multiple quantitative measures. MATERIALS AND METHODS: The analysis included all 165,988 trials registered at ClinicalTrials.gov as of April 30, 2014. To obtain benchmarks, the authors also analyzed 2 other medical corpora: (1) all 955 Health Topics articles from MedlinePlus and (2) a random sample of 100,000 clinician notes retrieved from an electronic health records system intended for conveying internal communication among medical professionals. The authors characterized each of the corpora using 4 surface metrics, and then applied 5 different scoring algorithms to assess their readability. The authors hypothesized that clinician notes would be most difficult to read, followed by trial descriptions and MedlinePlus Health Topics articles. RESULTS: Trial descriptions have the longest average sentence length (26.1 words) across all corpora; 65% of their words used are not covered by a basic medical English dictionary. In comparison, average sentence length of MedlinePlus Health Topics articles is 61% shorter, vocabulary size is 95% smaller, and dictionary coverage is 46% higher. All 5 scoring algorithms consistently rated CliniclTrials.gov trial descriptions the most difficult corpus to read, even harder than clinician notes. On average, it requires 18 years of education to properly understand these trial descriptions according to the results generated by the readability assessment algorithms. DISCUSSION AND CONCLUSION: Trial descriptions at CliniclTrials.gov are extremely difficult to read. Significant work is warranted to improve their readability in order to achieve CliniclTrials.gov's goal of facilitating information dissemination and subject recruitment. PMID- 26269537 TI - Correlates of Vaccine-Induced Protection against Mycobacterium tuberculosis Revealed in Comparative Analyses of Lymphocyte Populations. AB - A critical hindrance to the development of a novel vaccine against Mycobacterium tuberculosis is a lack of understanding of protective correlates of immunity and of host factors involved in a successful adaptive immune response. Studies from our group and others have used a mouse-based in vitro model system to assess correlates of protection. Here, using this coculture system and a panel of whole cell vaccines with varied efficacy, we developed a comprehensive approach to understand correlates of protection. We compared the gene and protein expression profiles of vaccine-generated immune peripheral blood lymphocytes (PBLs) to the profiles found in immune splenocytes. PBLs not only represent a clinically relevant cell population, but comparing the expression in these populations gave insight into compartmentally specific mechanisms of protection. Additionally, we performed a direct comparison of host responses induced when immune cells were cocultured with either the vaccine strain Mycobacterium bovis BCG or virulent M. tuberculosis. These comparisons revealed host-specific and bacterium-specific factors involved in protection against virulent M. tuberculosis. Most significantly, we identified a set of 13 core molecules induced in the most protective vaccines under all of the conditions tested. Further validation of this panel of mediators as a predictor of vaccine efficacy will facilitate vaccine development, and determining how each promotes adaptive immunity will advance our understanding of antimycobacterial immune responses. PMID- 26269538 TI - Androgen levels in women with various forms of ovarian dysfunction: associations with cardiometabolic features. AB - STUDY QUESTION: Are differences in androgen levels among women with various forms of ovarian dysfunction associated with cardiometabolic abnormalities? SUMMARY ANSWER: Androgen levels differed substantially between women with and without ovarian dysfunction, and increased androgen levels were associated with impaired cardiometabolic features in all women irrespective of their clinical condition. WHAT IS KNOWN ALREADY: Sex steroid hormones play important roles in the development of cardiovascular diseases (CVD). Extremes of low as well as high androgen levels have been associated with increased CVD risk in both men and women. STUDY DESIGN, SIZE, DURATION: This cross-sectional study included 680 women with polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), natural post-menopausal women (NM), or regular menstrual cycles (RC) (170 women per group). PARTICIPANTS/MATERIALS, SETTING, METHODS: Measurements of serum testosterone, androstenedione and dehydroepiandrosterone sulfate were performed using liquid chromatography-tandem mass spectrometry. Assessments were taken of body mass index (BMI), blood pressure, lipid profiles, glucose, insulin and SHBG, and the bioactive fraction of circulating testosterone was calculated using the free androgen index (FAI). MAIN RESULTS AND THE ROLE OF CHANCE: PCOS women were hyperandrogenic [median FAI = 4.9 (IQR 3.6-7.4)], and POI women were hypoandrogenic [FAI = 1.2 (0.8-1.7)], compared with RC women [FAI = 1.7 (1.1 2.8)], after adjustment for age, ethnicity, smoking and BMI (P < 0.001). After adjustment for age, there were no significant differences in androgens between POI and NM (P = 0.15) women and between NM and RC (P = 0.27) women, the latter indicating that chronological aging rather than ovarian aging influences the differences between pre- and post-menopausal women. A high FAI was associated with elevated triglycerides (beta log FAI for PCOS: 0.45, P < 0.001, POI: 0.25, P < 0.001, NM: 0.20, P = 0.002), insulin (beta log FAI for PCOS: 0.77, POI: 0.44, NM: 0.40, all P < 0.001), HOMA-IR (beta log FAI for PCOS: 0.82, POI: 0.46, NM: 0.47, all P < 0.001) and mean arterial pressure (beta log FAI for PCOS: 0.05, P = 0.002, POI: 0.07, P < 0.001, NM: 0.04, P = 0.04) in all women; with increased glucose (beta log FAI for PCOS: 0.05, P = 0.003, NM: 0.07, P < 0.001) and decreased high-density lipoprotein (beta log FAI for PCOS: -0.23, P < 0.001, NM: 0.09, P = 0.03) in PCOS and NM women; and with increased low-density lipoprotein (beta log FAI for POI: 0.083, P = 0.041) in POI women. Adjustment for BMI attenuated the observed associations. Associations between FAI and cardiometabolic features were the strongest in PCOS women, even after adjustment for BMI. LIMITATIONS, REASONS FOR CAUTION: Associations between androgen levels and cardiometabolic features were assessed in PCOS, POI and NM women only, due to a lack of available data in RC women. Due to the cross-sectional design of the current study, the potential associations between androgen levels and actual future cardiovascular events could not be assessed. WIDER IMPLICATIONS OF THE FINDINGS: This study affirms the potent effect of androgens on cardiometabolic features, indicating that androgens should indeed be regarded as important denominators of women's health. Future research regarding the role of androgens in the development of CVD and potential modulatory effects of BMI is required. STUDY FUNDING/COMPETING INTERESTS: N.M.P.D. is supported by the Dutch Heart Foundation (grant number 2013T083). L.J. and O.H.F. work in ErasmusAGE, a center for aging research across the life course, funded by Nestle Nutrition (Nestec Ltd), Metagenics Inc. and AXA. M.K. is supported by the AXA Research Fund. Nestle Nutrition (Nestec Ltd), Metagenics Inc. and AXA had no role in the design and conduct of the study; the collection, management, analysis and interpretation of the data; or the preparation, review or approval of the manuscript. J.S.E.L. has received fees and grant support from the following companies (in alphabetical order): Ferring, Merck-Serono, Merck Sharpe & Dome, Organon, Schering Plough and Serono. In the last 5 years, B.C.J.M.F. has received fees and grant support from the following companies (in alphabetic order); Actavis, COGI, Euroscreen, Ferring, Finox, Genovum, Gedeon-Richter, Merck-Serono, OvaScience, Pantharei Bioscience, PregLem, Roche, Uteron and Watson laboratories. With regard to potential conflicts of interest, there is nothing further to disclose. PMID- 26269539 TI - Is IVF-served two different ways-more cost-effective than IUI with controlled ovarian hyperstimulation? AB - STUDY QUESTION: What is the cost-effectiveness of in vitro fertilization (IVF) with conventional ovarian stimulation, single embryo transfer (SET) and subsequent cryocycles or IVF in a modified natural cycle (MNC) compared with intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH) as a first-line treatment in couples with unexplained subfertility and an unfavourable prognosis on natural conception?. SUMMARY ANSWER: Both IVF strategies are significantly more expensive when compared with IUI-COH, without being significantly more effective. In the comparison between IVF-MNC and IUI-COH, the latter is the dominant strategy. Whether IVF-SET is cost-effective depends on society's willingness to pay for an additional healthy child. WHAT IS KNOWN ALREADY: IUI-COH and IVF, either after conventional ovarian stimulation or in a MNC, are used as first-line treatments for couples with unexplained or mild male subfertility. As IUI-COH is less invasive, this treatment is usually offered before proceeding to IVF. Yet, as conventional IVF with SET may lead to higher pregnancy rates in fewer cycles for a lower multiple pregnancy rate, some have argued to start with IVF instead of IUI-COH. In addition, IVF in the MNC is considered to be a more patient friendly and less costly form of IVF. STUDY DESIGN, SIZE, DURATION: We performed a cost-effectiveness analysis alongside a randomized noninferiority trial. Between January 2009 and February 2012, 602 couples with unexplained infertility and a poor prognosis on natural conception were allocated to three cycles of IVF-SET including frozen embryo transfers, six cycles of IVF-MNC or six cycles of IUI-COH. These couples were followed until 12 months after randomization. PARTICIPANTS/MATERIALS, SETTING, METHODS: We collected data on resource use related to treatment, medication and pregnancy from the case report forms. We calculated unit costs from various sources. For each of the three strategies, we calculated the mean costs and effectiveness. Incremental cost-effectiveness ratios (ICER) were calculated for IVF-SET compared with IUI-COH and for IVF-MNC compared with IUI-COH. Nonparametric bootstrap resampling was used to investigate the effect of uncertainty in our estimates. MAIN RESULTS AND THE ROLE OF CHANCE: There were 104 healthy children (52%) born in the IVF-SET group, 83 (43%) the IVF-MNC group and 97 (47%) in the IUI-COH group. The mean costs per couple were ?7187 for IVF-SET, ?8206 for IVF-MNC and ?5070 for IUI-COH. Compared with IUI-COH, the costs for IVF-SET and IVF-MNC were significantly higher (mean differences ?2117; 95% CI: ?1544-?2657 and ?3136, 95% CI: ?2519-?3754, respectively).The ICER for IVF-SET compared with IUI-COH was ?43 375 for the birth of an additional healthy child. In the comparison of IVF-MNC to IUI-COH, the latter was the dominant strategy, i.e. more effective at lower costs. LIMITATIONS, REASONS FOR CAUTION: We only report on direct health care costs. The present analysis is limited to 12 months. WIDER IMPLICATIONS OF THE FINDINGS: Since we found no evidence in support of offering IVF as a first-line strategy in couples with unexplained and mild subfertility, IUI-COH should remain the treatment of first choice. STUDY FUNDING/COMPETING INTERESTS: The study was supported by a grant from ZonMw, the Netherlands Organization for Health Research and Development, (120620027) and a grant from Zorgverzekeraars Nederland, the Netherlands' association of health care insurers (09-003). TRIAL REGISTRATION NUMBER: Current Controlled Trials ISRCTN52843371; Nederlands Trial Register NTR939. PMID- 26269542 TI - Proteins of Unknown Biochemical Function: A Persistent Problem and a Roadmap to Help Overcome It. AB - The number of sequenced genomes is rapidly increasing, but functional annotation of the genes in these genomes lags far behind. Even in Arabidopsis (Arabidopsis thaliana), only approximately 40% of enzyme- and transporter-encoding genes have credible functional annotations, and this number is even lower in nonmodel plants. Functional characterization of unknown genes is a challenge, but various databases (e.g. for protein localization and coexpression) can be mined to provide clues. If homologous microbial genes exist-and about one-half the genes encoding unknown enzymes and transporters in Arabidopsis have microbial homologs cross-kingdom comparative genomics can powerfully complement plant-based data. Multiple lines of evidence can strengthen predictions and warrant experimental characterization. In some cases, relatively quick tests in genetically tractable microbes can determine whether a prediction merits biochemical validation, which is costly and demands specialized skills. PMID- 26269543 TI - Ligand-Mediated cis-Inhibition of Receptor Signaling in the Self-Incompatibility Response of the Brassicaceae. AB - The inhibition of self-pollination in self-incompatible Brassicaceae is based on allele-specific trans-activation of the highly polymorphic S-locus receptor kinase (SRK), which is displayed at the surface of stigma epidermal cells, by its even more polymorphic pollen coat-localized ligand, the S-locus cysteine-rich (SCR) protein. In an attempt to achieve constitutive activation of SRK and thus facilitate analysis of self-incompatibility (SI) signaling, we coexpressed an Arabidopsis lyrata SCR variant with its cognate SRK receptor in the stigma epidermal cells of Arabidopsis (Arabidopsis thaliana) plants belonging to the C24 accession, in which expression of SRK and SCR had been shown to exhibit a robust SI response. Contrary to expectation, however, coexpression of SRK and SCR was found to inhibit SRK-mediated signaling and to disrupt the SI response. This phenomenon, called cis-inhibition, is well documented in metazoans but has not as yet been reported for plant receptor kinases. We demonstrate that cis-inhibition of SRK, like its trans-activation, is based on allele-specific interaction between receptor and ligand. We also show that stigma-expressed SCR causes entrapment of its SRK receptor in the endoplasmic reticulum, thus disrupting the proper targeting of SRK to the plasma membrane, where the receptor would be available for productive interaction with its pollen coat-derived SCR ligand. Although based on an artificial cis-inhibition system, the results suggest novel strategies of pollination control for the generation of hybrid cultivars and large-scale seed production from hybrid plants in Brassicaceae seed crops and, more generally, for inhibiting cell surface receptor function and manipulating signaling pathways in plants. PMID- 26269544 TI - Targeted Mutagenesis, Precise Gene Editing, and Site-Specific Gene Insertion in Maize Using Cas9 and Guide RNA. AB - Targeted mutagenesis, editing of endogenous maize (Zea mays) genes, and site specific insertion of a trait gene using clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas)-guide RNA technology are reported in maize. DNA vectors expressing maize codon-optimized Streptococcus pyogenes Cas9 endonuclease and single guide RNAs were cointroduced with or without DNA repair templates into maize immature embryos by biolistic transformation targeting five different genomic regions: upstream of the liguleless1 (LIG1) gene, male fertility genes (Ms26 and Ms45), and acetolactate synthase (ALS) genes (ALS1 and ALS2). Mutations were subsequently identified at all sites targeted, and plants containing biallelic multiplex mutations at LIG1, Ms26, and Ms45 were recovered. Biolistic delivery of guide RNAs (as RNA molecules) directly into immature embryo cells containing preintegrated Cas9 also resulted in targeted mutations. Editing the ALS2 gene using either single-stranded oligonucleotides or double-stranded DNA vectors as repair templates yielded chlorsulfuron-resistant plants. Double-strand breaks generated by RNA-guided Cas9 endonuclease also stimulated insertion of a trait gene at a site near LIG1 by homology-directed repair. Progeny showed expected Mendelian segregation of mutations, edits, and targeted gene insertions. The examples reported in this study demonstrate the utility of Cas9-guide RNA technology as a plant genome editing tool to enhance plant breeding and crop research needed to meet growing agriculture demands of the future. PMID- 26269545 TI - Differential Role for Trehalose Metabolism in Salt-Stressed Maize. AB - Little is known about how salt impacts primary metabolic pathways of C4 plants, particularly related to kernel development and seed set. Osmotic stress was applied to maize (Zea mays) B73 by irrigation with increasing concentrations of NaCl from the initiation of floral organs until 3 d after pollination. At silking, photosynthesis was reduced to only 2% of control plants. Salt treatment was found to reduce spikelet growth, silk growth, and kernel set. Osmotic stress resulted in higher concentrations of sucrose (Suc) and hexose sugars in leaf, cob, and kernels at silking, pollination, and 3 d after pollination. Citric acid cycle intermediates were lower in salt-treated tissues, indicating that these sugars were unavailable for use in respiration. The sugar-signaling metabolite trehalose-6-phosphate was elevated in leaf, cob, and kernels at silking as a consequence of salt treatment but decreased thereafter even as Suc levels continued to rise. Interestingly, the transcripts of trehalose pathway genes were most affected by salt treatment in leaf tissue. On the other hand, transcripts of the SUCROSE NONFERMENTING-RELATED KINASE1 (SnRK1) marker genes were most affected in reproductive tissue. Overall, both source and sink strength are reduced by salt, and the data indicate that trehalose-6-phosphate and SnRK1 may have different roles in source and sink tissues. Kernel abortion resulting from osmotic stress is not from a lack of carbohydrate reserves but from the inability to utilize these energy reserves. PMID- 26269547 TI - Lack of Phosphatidylglycerol Inhibits Chlorophyll Biosynthesis at Multiple Sites and Limits Chlorophyllide Reutilization in Synechocystis sp. Strain PCC 6803. AB - The negatively charged lipid phosphatidylglycerol (PG) constitutes up to 10% of total lipids in photosynthetic membranes, and its deprivation in cyanobacteria is accompanied by chlorophyll (Chl) depletion. Indeed, radioactive labeling of the PG-depleted DeltapgsA mutant of Synechocystis sp. strain PCC 6803, which is not able to synthesize PG, proved the inhibition of Chl biosynthesis caused by restriction on the formation of 5-aminolevulinic acid and protochlorophyllide. Although the mutant accumulated chlorophyllide, the last Chl precursor, we showed that it originated from dephytylation of existing Chl and not from the block in the Chl biosynthesis. The lack of de novo-produced Chl under PG depletion was accompanied by a significantly weakened biosynthesis of both monomeric and trimeric photosystem I (PSI) complexes, although the decrease in cellular content was manifested only for the trimeric form. However, our analysis of DeltapgsA mutant, which lacked trimeric PSI because of the absence of the PsaL subunit, suggested that the virtual stability of monomeric PSI is a result of disintegration of PSI trimers. Interestingly, the loss of trimeric PSI was accompanied by accumulation of monomeric PSI associated with the newly synthesized CP43 subunit of photosystem II. We conclude that the absence of PG results in the inhibition of Chl biosynthetic pathway, which impairs synthesis of PSI, despite the accumulation of chlorophyllide released from the degraded Chl proteins. Based on the knowledge about the role of PG in prokaryotes, we hypothesize that the synthesis of Chl and PSI complexes are colocated in a membrane microdomain requiring PG for integrity. PMID- 26269548 TI - Compensatory plasticity in the olfactory epithelium: age, timing, and reversibility. AB - Like other biological systems, olfaction responds "homeostatically" to enduring change in the stimulus environment. This adaptive mechanism, referred to as compensatory plasticity, has been studied almost exclusively in developing animals. Thus it is unknown if this phenomenon is limited to ontogenesis and irreversible, characteristics common to some other forms of plasticity. Here we explore the effects of odor deprivation on the adult mouse olfactory epithelium (OE) using nasal plugs to eliminate nasal airflow unilaterally. Plugs were in place for 2-6 wk after which electroolfactograms (EOGs) were recorded from the occluded and open sides of the nasal cavity. Mean EOG amplitudes were significantly greater on the occluded than on the open side. The duration of plugging did not affect the results, suggesting that maximal compensation occurs within 2 wk or less. The magnitude of the EOG difference between the open and occluded side in plugged mice was comparable to adults that had undergone surgical naris occlusion as neonates. When plugs were removed after 4 wk followed by 2 wk of recovery, mean EOG amplitudes were not significantly different between the always-open and previously plugged sides of the nasal cavity suggesting that this form of plasticity is reversible. Taken together, these results suggest that compensatory plasticity is a constitutive mechanism of olfactory receptor neurons that allows these cells to recalibrate their stimulus-response relationship to fit the statistics of their current odor environment. PMID- 26269546 TI - The Identification of Maize and Arabidopsis Type I FLAVONE SYNTHASEs Links Flavones with Hormones and Biotic Interactions. AB - Flavones are a major group of flavonoids with diverse functions and are extensively distributed in land plants. There are two different classes of FLAVONE SYNTHASE (FNS) enzymes that catalyze the conversion of the flavanones into flavones. The FNSI class comprises soluble Fe(2+)/2-oxoglutarate-dependent dioxygenases, and FNSII enzymes are oxygen- and NADPH-dependent cytochrome P450 membrane-bound monooxygenases. Here, we describe the identification and characterization of FNSI enzymes from maize (Zea mays) and Arabidopsis (Arabidopsis thaliana). In maize, ZmFNSI-1 is expressed at significantly higher levels in silks and pericarps expressing the 3-deoxy flavonoid R2R3-MYB regulator P1, suggesting that ZmFNSI-1 could be the main enzyme for the synthesis of flavone O-glycosides. We also show here that DOWNY MILDEW RESISTANT6 (AtDMR6), the Arabidopsis homologous enzyme to ZmFNSI-1, has FNSI activity. While dmr6 mutants show loss of susceptibility to Pseudomonas syringae, transgenic dmr6 plants expressing ZmFNSI-1 show similar susceptibility to wild-type plants, demonstrating that ZmFNSI-1 can complement the mutant phenotype. AtDMR6 expression analysis showed a tissue- and developmental stage-dependent pattern, with high expression in cauline and senescing leaves. Finally, we show that Arabidopsis cauline and senescing leaves accumulate apigenin, demonstrating that Arabidopsis plants have an FNSI activity involved in the biosynthesis of flavones. The results presented here also suggest cross talk between the flavone and salicylic acid pathways in Arabidopsis; in this way, pathogens would induce flavones to decrease salicylic acid and, hence, increase susceptibility. PMID- 26269549 TI - Functional coupling between sodium-activated potassium channels and voltage dependent persistent sodium currents in cricket Kenyon cells. AB - In this study, we examined the functional coupling between Na(+)-activated potassium (KNa) channels and Na(+) influx through voltage-dependent Na(+) channels in Kenyon cells isolated from the mushroom body of the cricket Gryllus bimaculatus. Single-channel activity of KNa channels was recorded with the cell attached patch configuration. The open probability (Po) of KNa channels increased with increasing Na(+) concentration in a bath solution, whereas it decreased by the substitution of Na(+) with an equimolar concentration of Li(+). The Po of KNa channels was also found to be reduced by bath application of a high concentration of TTX (1 MUM) and riluzole (100 MUM), which inhibits both fast (INaf) and persistent (INaP) Na(+) currents, whereas it was unaffected by a low concentration of TTX (10 nM), which selectively blocks INaf. Bath application of Cd(2+) at a low concentration (50 MUM), as an inhibitor of INaP, also decreased the Po of KNa channels. Conversely, bath application of the inorganic Ca(2+) channel blockers Co(2+) and Ni(2+) at high concentrations (500 MUM) had little effect on the Po of KNa channels, although Cd(2+) (500 MUM) reduced the Po of KNa channels. Perforated whole cell clamp analysis further indicated the presence of sustained outward currents for which amplitude was dependent on the amount of Na(+) influx. Taken together, these results indicate that KNa channels could be activated by Na(+) influx passing through voltage-dependent persistent Na(+) channels. The functional significance of this coupling mechanism was discussed in relation to the membrane excitability of Kenyon cells and its possible role in the formation of long-term memory. PMID- 26269550 TI - Effects of changing skin mechanics on the differential sensitivity to surface compliance by tactile afferents in the human finger pad. AB - It is not known how changes in skin mechanics affect the responses of cutaneous mechanoreceptors in the finger pads to compression forces. We used venous occlusion to change the stiffness of the fingers and investigated whether this influenced the firing of low-threshold mechanoreceptors to surfaces of differing stiffness. Unitary recordings were made from 10 slowly adapting type I (SAI), 10 fast adapting type I (FAI) and 9 slowly adapting type II (SAII) units via tungsten microelectrodes inserted into the median nerve at the wrist. A servo controlled stimulator applied ramp-and-hold forces (1, 2, and 4 N) at a constant loading and unloading rate (2 N/s) via a flat 2.5-cm-diameter silicone disk over the center of the finger pad. Nine silicone disks (objects), varying in compliance, were used. Venous occlusion, produced by inflating a sphygmomanometer cuff around the upper arm to 40 +/- 5 mmHg, was used to induce swelling of the fingers and increase the compliance of the finger pulp. Venous occlusion had no effect on the firing rates of the SAI afferents, nor on the slopes of the relationship between mean firing rate and object compliance at each amplitude, but did significantly reduce the slopes for the FAI afferents. Although the SAII afferents possess a poor capacity to encode changes in object compliance, mean firing rates were significantly lower during venous occlusion. The finding that venous occlusion had no effect on the firing properties of SAI afferents indicates that these afferents preserve their capacity to encode changes in object compliance, despite changes in skin mechanics. PMID- 26269551 TI - Potassium currents dynamically set the recruitment and firing properties of F type motoneurons in neonatal mice. AB - In neonatal mice, fast- and slow-type motoneurons display different patterns of discharge. In response to a long liminal current pulse, the discharge is delayed up to several seconds in fast-type motoneurons and their firing frequency accelerates. In contrast, slow-type motoneurons discharge immediately, and their firing frequency decreases at the beginning of the pulse. Here, we identify the ionic currents that underlie the delayed firing of fast-type motoneurons. We find that the firing delay is caused by a combination of an A-like potassium current that transiently suppresses firing on a short time scale and a slowly inactivating potassium current that inhibits the discharge over a much longer time scale. We then show how these intrinsic currents dynamically shape the discharge threshold and the frequency-input function of fast-type motoneurons. These currents contribute to the orderly recruitment of motoneurons in neonates and might play a role in the postnatal maturation of motor units. PMID- 26269553 TI - Lack of depth constancy for grasping movements in both virtual and real environments. AB - Recent studies on visuomotor processes using virtual setups have suggested that actions are affected by similar biases as perceptual tasks. In particular, a strong lack of depth constancy is revealed, resembling biases in perceptual estimates of relative depth. With this study we aim to understand whether these findings are mostly caused by a lack of metric accuracy of the visuomotor system or by the limited cues provided by the use of virtual reality. We addressed this issue by comparing grasping movements towards a spherical object located at four distances (420, 450, 480, and 510 mm) performed in three conditions: 1) virtual, in which the target was a virtual object defined by binocular cues, 2) glow-in the-dark, in which the object was painted with luminous paint but no other cue was provided, and 3) full-cue, in which the movement was performed with the lights on and all the environmental information was available. Results revealed a striking effect of object distance on grip aperture equally in all three conditions. Specifically, grip aperture gradually decreased with increase in object distance, proving a consistent lack of depth constancy. These findings clearly demonstrate that systematic biases in grasping actions are not induced by the use of virtual environments and that action and perception may involve the same visual information, which does not engage a metric reconstruction of the scene. PMID- 26269552 TI - Network effects of deep brain stimulation. AB - The ability to differentially alter specific brain functions via deep brain stimulation (DBS) represents a monumental advance in clinical neuroscience, as well as within medicine as a whole. Despite the efficacy of DBS in the treatment of movement disorders, for which it is often the gold-standard therapy when medical management becomes inadequate, the mechanisms through which DBS in various brain targets produces therapeutic effects is still not well understood. This limited knowledge is a barrier to improving efficacy and reducing side effects in clinical brain stimulation. A field of study related to assessing the network effects of DBS is gradually emerging that promises to reveal aspects of the underlying pathophysiology of various brain disorders and their response to DBS that will be critical to advancing the field. This review summarizes the nascent literature related to network effects of DBS measured by cerebral blood flow and metabolic imaging, functional imaging, and electrophysiology (scalp and intracranial electroencephalography and magnetoencephalography) in order to establish a framework for future studies. PMID- 26269554 TI - Spinal 5-HT7 receptors induce phrenic motor facilitation via EPAC-mTORC1 signaling. AB - Spinal serotonin type 7 (5-HT7) receptors elicit complex effects on motor activity. Whereas 5-HT7 receptor activation gives rise to long-lasting phrenic motor facilitation (pMF), it also constrains 5-HT2 receptor-induced pMF via "cross-talk inhibition." We hypothesized that divergent cAMP-dependent signaling pathways give rise to these distinct 5-HT7 receptor actions. Specifically, we hypothesized that protein kinase A (PKA) mediates cross-talk inhibition of 5-HT2 receptor-induced pMF whereas 5-HT7 receptor-induced pMF results from exchange protein activated by cAMP (EPAC) signaling. Anesthetized, paralyzed, and ventilated rats receiving intrathecal (C4) 5-HT7 receptor agonist (AS-19) injections expressed pMF for >90 min, an effect abolished by pretreatment with a selective EPAC inhibitor (ESI-05) but not a selective PKA inhibitor (KT-5720). Furthermore, intrathecal injections of a selective EPAC activator (8-pCPT-2'-Me cAMP) were sufficient to elicit pMF. Finally, spinal mammalian target of rapamycin complex-1 (mTORC1) inhibition via intrathecal rapamycin abolished 5-HT7 receptor- and EPAC-induced pMF, demonstrating that spinal 5-HT7 receptors elicit pMF by an EPAC-mTORC1 signaling pathway. Thus 5-HT7 receptors elicit and constrain spinal phrenic motor plasticity via distinct signaling mechanisms that diverge at cAMP (EPAC vs. PKA). Selective manipulation of these molecules may enable refined regulation of serotonin-dependent spinal motor plasticity for therapeutic advantage. PMID- 26269555 TI - Spike timing precision changes with spike rate adaptation in the owl's auditory space map. AB - Spike rate adaptation (SRA) is a continuing change of responsiveness to ongoing stimuli, which is ubiquitous across species and levels of sensory systems. Under SRA, auditory responses to constant stimuli change over time, relaxing toward a long-term rate often over multiple timescales. With more variable stimuli, SRA causes the dependence of spike rate on sound pressure level to shift toward the mean level of recent stimulus history. A model based on subtractive adaptation (Benda J, Hennig RM. J Comput Neurosci 24: 113-136, 2008) shows that changes in spike rate and level dependence are mechanistically linked. Space-specific neurons in the barn owl's midbrain, when recorded under ketamine-diazepam anesthesia, showed these classical characteristics of SRA, while at the same time exhibiting changes in spike timing precision. Abrupt level increases of sinusoidally amplitude-modulated (SAM) noise initially led to spiking at higher rates with lower temporal precision. Spike rate and precision relaxed toward their long-term values with a time course similar to SRA, results that were also replicated by the subtractive model. Stimuli whose amplitude modulations (AMs) were not synchronous across carrier frequency evoked spikes in response to stimulus envelopes of a particular shape, characterized by the spectrotemporal receptive field (STRF). Again, abrupt stimulus level changes initially disrupted the temporal precision of spiking, which then relaxed along with SRA. We suggest that shifts in latency associated with stimulus level changes may differ between carrier frequency bands and underlie decreased spike precision. Thus SRA is manifest not simply as a change in spike rate but also as a change in the temporal precision of spiking. PMID- 26269556 TI - Lower neuronal variability in the monkey dorsolateral prefrontal than posterior parietal cortex. AB - The dorsolateral prefrontal and posterior parietal cortex are two brain areas involved in cognitive functions such as spatial attention and working memory. When tested with identical tasks, only subtle differences in firing rate are present between neurons recorded in the two areas. In this article we report that major differences in neuronal variability characterize the two areas during working memory. The Fano factors of spike counts in dorsolateral prefrontal neurons were consistently lower than those of the posterior parietal cortex across a range of tasks, epochs, and conditions in the same monkeys. Variability differences were observed despite minor differences in firing rates between the two areas in the tasks tested and higher overall firing rate in the prefrontal than in the posterior parietal sample. Other measures of neuronal discharge variability, such as the coefficient of variation of the interspike interval, displayed the same pattern of lower prefrontal variability. Fano factor values were negatively correlated with performance in the working memory task, suggesting that higher neuronal variability was associated with diminished task performance. The results indicate that information involving remembered stimuli is more reliably represented in the prefrontal than the posterior parietal cortex based on the variability of neuronal responses, and suggest functional differentiation between the two areas beyond differences in firing rate. PMID- 26269557 TI - Overlapping representations for reach depth and direction in caudal superior parietal lobule of macaques. AB - Reaching movements in the real world have typically a direction and a depth component. Despite numerous behavioral studies, there is no consensus on whether reach coordinates are processed in separate or common visuomotor channels. Furthermore, the neural substrates of reach depth in parietal cortex have been ignored in most neurophysiological studies. In the medial posterior parietal area V6A, we recently demonstrated the strong presence of depth signals and the extensive convergence of depth and direction information on single neurons during all phases of a fixate-to-reach task in 3-dimensional (3D) space. Using the same task, in the present work we examined the processing of direction and depth information in area PEc of the caudal superior parietal lobule (SPL) in three Macaca fascicularis monkeys. Across the task, depth and direction had a similar, high incidence of modulatory effect. The effect of direction was stronger than depth during the initial fixation period. As the task progressed toward arm movement execution, depth tuning became more prominent than directional tuning and the number of cells modulated by both depth and direction increased significantly. Neurons tuned by depth showed a small bias for far peripersonal space. Cells with directional modulations were more frequently tuned toward contralateral spatial locations, but ipsilateral space was also represented. These findings, combined with results from neighboring areas V6A and PE, support a rostral-to-caudal gradient of overlapping representations for reach depth and direction in SPL. These findings also support a progressive change from visuospatial (vergence angle) to somatomotor representations of 3D space in SPL. PMID- 26269558 TI - Membrane potential dynamics of populations of cortical neurons during auditory streaming. AB - How a mixture of acoustic sources is perceptually organized into discrete auditory objects remains unclear. One current hypothesis postulates that perceptual segregation of different sources is related to the spatiotemporal separation of cortical responses induced by each acoustic source or stream. In the present study, the dynamics of subthreshold membrane potential activity were measured across the entire tonotopic axis of the rodent primary auditory cortex during the auditory streaming paradigm using voltage-sensitive dye imaging. Consistent with the proposed hypothesis, we observed enhanced spatiotemporal segregation of cortical responses to alternating tone sequences as their frequency separation or presentation rate was increased, both manipulations known to promote stream segregation. However, across most streaming paradigm conditions tested, a substantial cortical region maintaining a response to both tones coexisted with more peripheral cortical regions responding more selectively to one of them. We propose that these coexisting subthreshold representation types could provide neural substrates to support the flexible switching between the integrated and segregated streaming percepts. PMID- 26269559 TI - Auditory midbrain representation of a break in interaural correlation. AB - The auditory peripheral system filters broadband sounds into narrowband waves and decomposes narrowband waves into quickly varying temporal fine structures (TFSs) and slowly varying envelopes. When a noise is presented binaurally (with the interaural correlation being 1), human listeners can detect a transient break in interaural correlation (BIC), which does not alter monaural inputs substantially. The central correlates of BIC are unknown. This study examined whether phase locking-based frequency-following responses (FFRs) of neuron populations in the rat auditory midbrain [inferior colliculus (IC)] to interaurally correlated steady-state narrowband noises are modulated by introduction of a BIC. The results showed that the noise-induced FFR exhibited both a TFS component (FFRTFS) and an envelope component (FFREnv), signaling the center frequency and bandwidth, respectively. Introduction of either a BIC or an interaurally correlated amplitude gap (which had the summated amplitude matched to the BIC) significantly reduced both FFRTFS and FFREnv. However, the BIC-induced FFRTFS reduction and FFREnv reduction were not correlated with the amplitude gap-induced FFRTFS reduction and FFREnv reduction, respectively. Thus, although introduction of a BIC does not affect monaural inputs, it causes a temporary reduction in sustained responses of IC neuron populations to the noise. This BIC-induced FFR reduction is not based on a simple linear summation of noise signals. PMID- 26269560 TI - Motor signatures in autism spectrum disorder: the importance of variability. AB - In a recent study, Wang et al. (J Neurophysiol 113: 1989-2001, 2015) used a precision grip force control task to unveil the contribution of feedforward and feedback mechanisms to sensorimotor dysfunction in autism spectrum disorder (ASD). Impairment of both motor control mechanisms was observed, along with significant variability in the motor response. In this Neuro Forum article we discuss these findings within the conceptual framework of the grasping circuit and within the broader context of clinical and research applications based on motor behavior. PMID- 26269561 TI - All Data Are Not Equal. PMID- 26269562 TI - Variations Among Medicare Beneficiaries Living in Different Settings: Demographics, Health Status, and Service Use. AB - Older people with complex health issues and needs for functional support are increasingly living in different types of residential care environments as alternatives to nursing homes. This study aims to compare the demographics and health-care expenditures of Medicare beneficiaries by the setting in which they live: nursing homes, residential care settings, and at home using data from the 2002 to 2010 Medicare Current Beneficiary Study (MCBS), a nationally representative survey of the Medicare population. All Medicare beneficiaries aged 65 years or older who participated in the fall MCBS interview (years 2002-2010) and were alive for the full year (N = 83,507) were included in the sample. We found that there is a gradient in health status, physical and cognitive functioning, and health-care use and spending across settings. Minority elderly are overrepresented in facilities and underrepresented in alternative living settings. PMID- 26269563 TI - DNA Methylation Predicts Progression of Human Gastric Lesions. AB - BACKGROUND: Development of the intestinal subtype of gastric adenocarcinoma is marked by a progression of histopathologic lesions. Residents of the Andean regions of Colombia are at high risk for gastric cancer. METHODS: A cohort of 976 Colombian subjects was followed over 16 years examining effects of Helicobacter pylori eradication and treatment with antioxidants on progression of lesions. We performed methylation analysis of DNA from baseline antral biopsies from 104 subjects for whom follow-up data were available for at least 12 years. Methylation was quantitated for AMPH, CDKN2A, CDH1, EN1, EMX1, NKX6-1, PCDH10, RPRM, RSPO2, SORCS3, ZIC1, and ZNF610 genes, using Pyrosequencing. RESULTS: Levels of DNA methylation were associated with baseline diagnosis for AMPH, EMX1, RPRM, RSPO2, SORCS3, and ZNF610. After adjusting for baseline diagnosis and H. pylori infection, methylation levels of AMPH, PCDH10, RSPO2, and ZNF610 had progression coefficients that increased and P values that decreased over 6, 12, and 16 years. Methylation for SORCS3 was associated with progression at all 3 time points but without the continual strengthening of the effect. Scores for mononuclear leukocytes, polymorphonuclear leukocytes, or intraepithelial lymphocytes were unrelated to progression. CONCLUSIONS: Methylation levels of AMPH, PCDH10, RSPO2, SORCS3, and ZNF610 predict progression of gastric lesions independent of the effect of duration of H. pylori infection, baseline diagnosis, gender of the patient, or scores for mononuclear leukocytes, polymorphonuclear leukocytes, or intraepithelial lymphocytes. IMPACT: DNA methylation levels in AMPH, PCDH10, RSPO2, SORCS3, and ZNF610 may contribute to identification of persons with gastric lesions likely to progress. PMID- 26269565 TI - Julie A. Ross: In Memoriam (1961-2015). PMID- 26269564 TI - Serum Retinol and Carotenoid Concentrations and Prostate Cancer Risk: Results from the Prostate Cancer Prevention Trial. AB - BACKGROUND: Findings from epidemiologic studies examining associations of serum retinol and carotenoids with prostate cancer risk have been inconsistent. This case-control study nested in the Prostate Cancer Prevention Trial evaluated associations of serum retinol and carotenoids with total, low-, and high-grade prostate cancer risk in a highly screened study population. METHODS: We used logistic regression adjusting for age, family history of prostate cancer, race, body mass index, and serum cholesterol to estimate ORs and 95% confidence intervals (CI) of prostate cancer by quartiles of serum retinol and carotenoids, separately in the placebo (975 cases/1,009 frequency-matched controls) and finasteride (708 cases/743 frequency-matched controls) arms of the trial. RESULTS: Serum retinol concentrations were associated with increased risk of total prostate cancer [OR (95% CI) comparing the highest quartile of serum retinol with the lowest: 1.30 (1.00-1.68)] and high-grade prostate cancer [OR (95% CI), 1.74 (1.14-2.68)] in the placebo arm of the trial only. Also in the placebo arm, there was a moderate positive association of alpha-carotene with risk of total prostate cancer [OR (95% CI), 1.32 (1.01-1.73)]. None of the other carotenoids was associated with prostate cancer risk in the placebo arm. No associations were observed for retinol and carotenoids in the finasteride arm. CONCLUSION: In the placebo arm of this prospective study, high serum retinol and alpha-carotene concentrations were associated with increased risk of total and high-grade prostate cancers. IMPACT: Men with higher levels of serum retinol and alpha-carotene may be at increased risk for prostate cancer. PMID- 26269567 TI - Examining the reaction of NO and H2S and the possible cross-talk between the two signaling pathways. PMID- 26269566 TI - Supplementation of l-Alanyl-l-Glutamine and Fish Oil Improves Body Composition and Quality of Life in Patients With Chronic Heart Failure. AB - BACKGROUND: Skeletal muscle dysfunction and exercise intolerance are clinical hallmarks of patients with heart failure. These have been linked to a progressive catabolic state, skeletal muscle inflammation, and impaired oxidative metabolism. Previous studies suggest beneficial effects of omega-3 polyunsaturated fatty acids and glutamine on exercise performance and muscle protein balance. METHODS AND RESULTS: In a randomized double-blind, placebo-controlled trial, 31 patients with heart failure were randomized to either l-alanyl-l-glutamine (8 g/d) and polyunsaturated fatty acid (6.5 g/d) or placebo (safflower oil and milk powder) for 3 months. Cardiopulmonary exercise testing, dual-energy x-ray absorptiometry, 6-minute walk test, hand grip strength, functional muscle testing, echocardiography, and quality of life and lateral quadriceps muscle biopsy were performed at baseline and at follow-up. Oxidative capacity and metabolic gene expression were analyzed on muscle biopsies. No differences in muscle function, echocardiography, 6-minute walk test, or hand grip strength and a nonsignificant increase in peak VO2 in the treatment group were found. Lean body mass increased and quality of life improved in the active treatment group. Molecular analysis revealed no differences in muscle fiber composition, fiber cross-sectional area, gene expression of metabolic marker genes (PGC1alpha, CPT1, PDK4, and GLUT4), and skeletal muscle oxidative capacity. CONCLUSIONS: The combined supplementation of l-alanyl-l-glutamine and polyunsaturated fatty acid did not improve exercise performance or muscle function but increased lean body mass and quality of life in patients with chronic stable heart failure. These findings suggest potentially beneficial effects of high-dose nutritional polyunsaturated fatty acids and amino acid supplementations in patients with chronic stable heart failure. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01534663. PMID- 26269568 TI - Computational design and experimental verification of a symmetric protein homodimer. AB - Homodimers are the most common type of protein assembly in nature and have distinct features compared with heterodimers and higher order oligomers. Understanding homodimer interactions at the atomic level is critical both for elucidating their biological mechanisms of action and for accurate modeling of complexes of unknown structure. Computation-based design of novel protein-protein interfaces can serve as a bottom-up method to further our understanding of protein interactions. Previous studies have demonstrated that the de novo design of homodimers can be achieved to atomic-level accuracy by beta-strand assembly or through metal-mediated interactions. Here, we report the design and experimental characterization of a alpha-helix-mediated homodimer with C2 symmetry based on a monomeric Drosophila engrailed homeodomain scaffold. A solution NMR structure shows that the homodimer exhibits parallel helical packing similar to the design model. Because the mutations leading to dimer formation resulted in poor thermostability of the system, design success was facilitated by the introduction of independent thermostabilizing mutations into the scaffold. This two-step design approach, function and stabilization, is likely to be generally applicable, especially if the desired scaffold is of low thermostability. PMID- 26269569 TI - Small-molecule-directed, efficient generation of retinal pigment epithelium from human pluripotent stem cells. AB - Age-related macular degeneration (AMD) is associated with dysfunction and death of retinal pigment epithelial (RPE) cells. Cell-based approaches using RPE-like cells derived from human pluripotent stem cells (hPSCs) are being developed for AMD treatment. However, most efficient RPE differentiation protocols rely on complex, stepwise treatments and addition of growth factors, whereas small molecule-only approaches developed to date display reduced yields. To identify new compounds that promote RPE differentiation, we developed and performed a high throughput quantitative PCR screen complemented by a novel orthogonal human induced pluripotent stem cell (hiPSC)-based RPE reporter assay. Chetomin, an inhibitor of hypoxia-inducible factors, was found to strongly increase RPE differentiation; combination with nicotinamide resulted in conversion of over one half of the differentiating cells into RPE. Single passage of the whole culture yielded a highly pure hPSC-RPE cell population that displayed many of the morphological, molecular, and functional characteristics of native RPE. PMID- 26269571 TI - Correction for Jimenez et al., Dynamics of gene circuits shapes evolvability. PMID- 26269572 TI - Correction for Hristov et al., An inhibitor persistently decreased enteric methane emission from dairy cows with no negative effect on milk production. PMID- 26269570 TI - Comparison of predicted and actual consequences of missense mutations. AB - Each person's genome sequence has thousands of missense variants. Practical interpretation of their functional significance must rely on computational inferences in the absence of exhaustive experimental measurements. Here we analyzed the efficacy of these inferences in 33 de novo missense mutations revealed by sequencing in first-generation progeny of N-ethyl-N-nitrosourea treated mice, involving 23 essential immune system genes. PolyPhen2, SIFT, MutationAssessor, Panther, CADD, and Condel were used to predict each mutation's functional importance, whereas the actual effect was measured by breeding and testing homozygotes for the expected in vivo loss-of-function phenotype. Only 20% of mutations predicted to be deleterious by PolyPhen2 (and 15% by CADD) showed a discernible phenotype in individual homozygotes. Half of all possible missense mutations in the same 23 immune genes were predicted to be deleterious, and most of these appear to become subject to purifying selection because few persist between separate mouse substrains, rodents, or primates. Because defects in immune genes could be phenotypically masked in vivo by compensation and environment, we compared inferences by the same tools with the in vitro phenotype of all 2,314 possible missense variants in TP53; 42% of mutations predicted by PolyPhen2 to be deleterious (and 45% by CADD) had little measurable consequence for TP53-promoted transcription. We conclude that for de novo or low-frequency missense mutations found by genome sequencing, half those inferred as deleterious correspond to nearly neutral mutations that have little impact on the clinical phenotype of individual cases but will nevertheless become subject to purifying selection. PMID- 26269573 TI - Scalable synthesis of sequence-defined, unimolecular macromolecules by Flow-IEG. AB - We report a semiautomated synthesis of sequence and architecturally defined, unimolecular macromolecules through a marriage of multistep flow synthesis and iterative exponential growth (Flow-IEG). The Flow-IEG system performs three reactions and an in-line purification in a total residence time of under 10 min, effectively doubling the molecular weight of an oligomeric species in an uninterrupted reaction sequence. Further iterations using the Flow-IEG system enable an exponential increase in molecular weight. Incorporating a variety of monomer structures and branching units provides control over polymer sequence and architecture. The synthesis of a uniform macromolecule with a molecular weight of 4,023 g/mol is demonstrated. The user-friendly nature, scalability, and modularity of Flow-IEG provide a general strategy for the automated synthesis of sequence-defined, unimolecular macromolecules. Flow-IEG is thus an enabling tool for theory validation, structure-property studies, and advanced applications in biotechnology and materials science. PMID- 26269574 TI - Molecular Basis of Hypokalemia-Induced Ventricular Fibrillation. AB - BACKGROUND: Hypokalemia is known to promote ventricular arrhythmias, especially in combination with class III antiarrhythmic drugs like dofetilide. Here, we evaluated the underlying molecular mechanisms. METHODS AND RESULTS: Arrhythmias were recorded in isolated rabbit and rat hearts or patch-clamped ventricular myocytes exposed to hypokalemia (1.0-3.5 mmol/L) in the absence or presence of dofetilide (1 MUmol/L). Spontaneous early afterdepolarizations (EADs) and ventricular tachycardia/fibrillation occurred in 50% of hearts at 2.7 mmol/L [K] in the absence of dofetilide and 3.3 mmol/L [K] in its presence. Pretreatment with the Ca-calmodulin kinase II (CaMKII) inhibitor KN-93, but not its inactive analogue KN-92, abolished EADs and hypokalemia-induced ventricular tachycardia/fibrillation, as did the selective late Na current (INa) blocker GS 967. In intact hearts, moderate hypokalemia (2.7 mmol/L) significantly increased tissue CaMKII activity. Computer modeling revealed that EAD generation by hypokalemia (with or without dofetilide) required Na-K pump inhibition to induce intracellular Na and Ca overload with consequent CaMKII activation enhancing late INa and the L-type Ca current. K current suppression by hypokalemia and dofetilide alone in the absence of CaMKII activation were ineffective at causing EADs. CONCLUSIONS: We conclude that Na-K pump inhibition by even moderate hypokalemia plays a critical role in promoting EAD-mediated arrhythmias by inducing a positive feedback cycle activating CaMKII and enhancing late INa. Class III antiarrhythmic drugs like dofetilide sensitize the heart to this positive feedback loop. PMID- 26269575 TI - The Race Is On: Early Determination of Neuroprognosis After Cardiac Arrest. PMID- 26269576 TI - Continuous Amplitude-Integrated Electroencephalographic Monitoring Is a Useful Prognostic Tool for Hypothermia-Treated Cardiac Arrest Patients. AB - BACKGROUND: Modern treatments have improved the survival rate following cardiac arrest, but prognostication remains a challenge. We examined the prognostic value of continuous electroencephalography according to time by performing amplitude integrated electroencephalography on patients with cardiac arrest receiving therapeutic hypothermia. METHODS AND RESULTS: We prospectively studied 130 comatose patients treated with hypothermia from September 2010 to April 2013. We evaluated the time to normal trace (TTNT) as a neurological outcome predictor and determined the prognostic value of burst suppression and status epilepticus, with a particular focus on their time of occurrence. Fifty-five patients exhibited a cerebral performance category score of 1 to 2. The area under the curve for TTNT was 0.97 (95% confidence interval, 0.92-0.99), and the sensitivity and specificity of TTNT<24 hours after resuscitation as a threshold for predicting good neurological outcome were 94.6% (95% confidence interval, 84.9%-98.9%) and 90.7% (95% confidence interval, 81.7%-96.2%), respectively. The threshold displaying 100% specificity for predicting poor neurological outcome was TTNT>36 hours. Burst suppression and status epilepticus predicted poor neurological outcome (positive predictive value of 98.3% and 96.4%, respectively). The combination of these factors predicted a negative outcome at a median of 6.2 hours after resuscitation (sensitivity and specificity of 92.0% and 96.4%, respectively). CONCLUSIONS: A TTNT<24 hours was associated with good neurological outcome. The lack of normal trace development within 36 hours, status epilepticus, and burst suppression were predictors of poor outcome. The combination of these negative predictors may improve their prognostic performance at an earlier stage. PMID- 26269577 TI - PDI reductase acts on Akita mutant proinsulin to initiate retrotranslocation along the Hrd1/Sel1L-p97 axis. AB - In mutant INS gene-induced diabetes of youth (MIDY), characterized by insulin deficiency, MIDY proinsulin mutants misfold and fail to exit the endoplasmic reticulum (ER). Moreover, these mutants bind and block ER exit of wild-type (WT) proinsulin, inhibiting insulin production. The ultimate fate of ER-entrapped MIDY mutants is unclear, but previous studies implicated ER-associated degradation (ERAD), a pathway that retrotranslocates misfolded ER proteins to the cytosol for proteasomal degradation. Here we establish key ERAD machinery components used to triage the Akita proinsulin mutant, including the Hrd1-Sel1L membrane complex, which conducts Akita proinsulin from the ER lumen to the cytosol, and the p97 ATPase, which couples the cytosolic arrival of proinsulin with its proteasomal degradation. Surprisingly, we find that protein disulfide isomerase (PDI), the major protein oxidase of the ER lumen, engages Akita proinsulin in a novel way, reducing proinsulin disulfide bonds and priming the Akita protein for ERAD. Efficient PDI engagement of Akita proinsulin appears linked to the availability of Hrd1, suggesting that retrotranslocation is coordinated on the lumenal side of the ER membrane. We believe that, in principle, this form of diabetes could be alleviated by enhancing the targeting of MIDY mutants for ERAD to restore WT insulin production. PMID- 26269578 TI - RdgB2 is required for dim-light input into intrinsically photosensitive retinal ganglion cells. AB - A subset of retinal ganglion cells is intrinsically photosensitive (ipRGCs) and contributes directly to the pupillary light reflex and circadian photoentrainment under bright-light conditions. ipRGCs are also indirectly activated by light through cellular circuits initiated in rods and cones. A mammalian homologue (RdgB2) of a phosphoinositide transfer/exchange protein that functions in Drosophila phototransduction is expressed in the retinal ganglion cell layer. This raised the possibility that RdgB2 might function in the intrinsic light response in ipRGCs, which depends on a cascade reminiscent of Drosophila phototransduction. Here we found that under high light intensities, RdgB2(-/-) mutant mice showed normal pupillary light responses and circadian photoentrainment. Consistent with this behavioral phenotype, the intrinsic light responses of ipRGCs in RdgB2(-/-) were indistinguishable from wild-type. In contrast, under low-light conditions, RdgB2(-/-) mutants displayed defects in both circadian photoentrainment and the pupillary light response. The RdgB2 protein was not expressed in ipRGCs but was in GABAergic amacrine cells, which provided inhibitory feedback onto bipolar cells. We propose that RdgB2 is required in a cellular circuit that transduces light input from rods to bipolar cells that are coupled to GABAergic amacrine cells and ultimately to ipRGCs, thereby enabling ipRGCs to respond to dim light. PMID- 26269579 TI - Centrosome-intrinsic mechanisms modulate centrosome integrity during fever. AB - The centrosome is critical for cell division, ciliogenesis, membrane trafficking, and immunological synapse function. The immunological synapse is part of the immune response, which is often accompanied by fever/heat stress (HS). Here we provide evidence that HS causes deconstruction of all centrosome substructures primarily through degradation by centrosome-associated proteasomes. This renders the centrosome nonfunctional. Heat-activated degradation is centrosome selective, as other nonmembranous organelles (midbody, kinetochore) and membrane-bounded organelles (mitochondria) remain largely intact. Heat-induced centrosome inactivation was rescued by targeting Hsp70 to the centrosome. In contrast, Hsp70 excluded from the centrosome via targeting to membranes failed to rescue, as did chaperone inactivation. This indicates that there is a balance between degradation and chaperone rescue at the centrosome after HS. This novel mechanism of centrosome regulation during fever contributes to immunological synapse formation. Heat-induced centrosome inactivation is a physiologically relevant event, as centrosomes in leukocytes of febrile patients are disrupted. PMID- 26269580 TI - TbetaRIII independently binds type I and type II TGF-beta receptors to inhibit TGF-beta signaling. AB - Transforming growth factor-beta (TGF-beta) receptor oligomerization has important roles in signaling. Complex formation among type I and type II (TbetaRI and TbetaRII) TGF-beta receptors is well characterized and is essential for signal transduction. However, studies on their interactions with the type III TGF-beta coreceptor (TbetaRIII) in live cells and their effects on TGF-beta signaling are lacking. Here we investigated the homomeric and heteromeric interactions of TbetaRIII with TbetaRI and TbetaRII in live cells by combining IgG-mediated patching/immobilization of a given TGF-beta receptor with fluorescence recovery after photobleaching studies on the lateral diffusion of a coexpressed receptor. Our studies demonstrate that TbetaRIII homo-oligomerization is indirect and depends on its cytoplasmic domain interactions with scaffold proteins (mainly GIPC). We show that TbetaRII and TbetaRI bind independently to TbetaRIII, whereas TbetaRIII augments TbetaRI/TbetaRII association, suggesting that TbetaRI and TbetaRII bind to TbetaRIII simultaneously but not as a complex. TbetaRIII expression inhibited TGF-beta-mediated Smad2/3 signaling in MDA-MB-231 cell lines, an effect that depended on the TbetaRIII cytoplasmic domain and did not require TbetaRIII ectodomain shedding. We propose that independent binding of TbetaRI and TbetaRII to TbetaRIII competes with TbetaRI/TbetaRII signaling complex formation, thus inhibiting TGF-beta-mediated Smad signaling. PMID- 26269581 TI - Lipid partitioning at the nuclear envelope controls membrane biogenesis. AB - Partitioning of lipid precursors between membranes and storage is crucial for cell growth, and its disruption underlies pathologies such as cancer, obesity, and type 2 diabetes. However, the mechanisms and signals that regulate this process are largely unknown. In yeast, lipid precursors are mainly used for phospholipid synthesis in nutrient-rich conditions in order to sustain rapid proliferation but are redirected to triacylglycerol (TAG) stored in lipid droplets during starvation. Here we investigate how cells reprogram lipid metabolism in the endoplasmic reticulum. We show that the conserved phosphatidate (PA) phosphatase Pah1, which generates diacylglycerol from PA, targets a nuclear membrane subdomain that is in contact with growing lipid droplets and mediates TAG synthesis. We find that cytosol acidification activates the master regulator of Pah1, the Nem1-Spo7 complex, thus linking Pah1 activity to cellular metabolic status. In the absence of TAG storage capacity, Pah1 still binds the nuclear membrane, but lipid precursors are redirected toward phospholipids, resulting in nuclear deformation and a proliferation of endoplasmic reticulum membrane. We propose that, in response to growth signals, activation of Pah1 at the nuclear envelope acts as a switch to control the balance between membrane biogenesis and lipid storage. PMID- 26269582 TI - Atypical protein kinase C induces cell transformation by disrupting Hippo/Yap signaling. AB - Epithelial cells are major sites of malignant transformation. Atypical protein kinase C (aPKC) isoforms are overexpressed and activated in many cancer types. Using normal, highly polarized epithelial cells (MDCK and NMuMG), we report that aPKC gain of function overcomes contact inhibited growth and is sufficient for a transformed epithelial phenotype. In 2D cultures, aPKC induced cells to grow as stratified epithelia, whereas cells grew as solid spheres of nonpolarized cells in 3D culture. aPKC associated with Mst1/2, which uncoupled Mst1/2 from Lats1/2 and promoted nuclear accumulation of Yap1. Of importance, Yap1 was necessary for aPKC-mediated overgrowth but did not restore cell polarity defects, indicating that the two are separable events. In MDCK cells, Yap1 was sequestered to cell cell junctions by Amot, and aPKC overexpression resulted in loss of Amot expression and a spindle-like cell phenotype. Reexpression of Amot was sufficient to restore an epithelial cobblestone appearance, Yap1 localization, and growth control. In contrast, the effect of aPKC on Hippo/Yap signaling and overgrowth in NMuMG cells was independent of Amot. Finally, increased expression of aPKC in human cancers strongly correlated with increased nuclear accumulation of Yap1, indicating that the effect of aPKC on transformed growth by deregulating Hippo/Yap1 signaling may be clinically relevant. PMID- 26269583 TI - Single-cell analysis of circadian dynamics in tissue explants. AB - Tracking molecular dynamics in single cells in vivo is instrumental to understanding how cells act and interact in tissues. Current tissue imaging approaches focus on short-term observation and typically nonendogenous or implanted samples. Here we develop an experimental and computational setup that allows for single-cell tracking of a transcriptional reporter over a period of >1 wk in the context of an intact tissue. We focus on the peripheral circadian clock as a model system and measure the circadian signaling of hundreds of cells from two tissues. The circadian clock is an autonomous oscillator whose behavior is well described in isolated cells, but in situ analysis of circadian signaling in single cells of peripheral tissues is as-yet uncharacterized. Our approach allowed us to investigate the oscillatory properties of individual clocks, determine how these properties are maintained among different cells, and assess how they compare to the population rhythm. These experiments, using a wide-field microscope, a previously generated reporter mouse, and custom software to track cells over days, suggest how many signaling pathways might be quantitatively characterized in explant models. PMID- 26269584 TI - Hcm1 integrates signals from Cdk1 and calcineurin to control cell proliferation. AB - Cyclin-dependent kinase (Cdk1) orchestrates progression through the cell cycle by coordinating the activities of cell-cycle regulators. Although phosphatases that oppose Cdk1 are likely to be necessary to establish dynamic phosphorylation, specific phosphatases that target most Cdk1 substrates have not been identified. In budding yeast, the transcription factor Hcm1 activates expression of genes that regulate chromosome segregation and is critical for maintaining genome stability. Previously we found that Hcm1 activity and degradation are stimulated by Cdk1 phosphorylation of distinct clusters of sites. Here we show that, upon exposure to environmental stress, the phosphatase calcineurin inhibits Hcm1 by specifically removing activating phosphorylations and that this regulation is important for cells to delay proliferation when they encounter stress. Our work identifies a mechanism by which proliferative signals from Cdk1 are removed in response to stress and suggests that Hcm1 functions as a rheostat that integrates stimulatory and inhibitory signals to control cell proliferation. PMID- 26269585 TI - A phosphoinositide-binding cluster in cavin1 acts as a molecular sensor for cavin1 degradation. AB - Caveolae are abundant surface organelles implicated in a range of cellular processes. Two classes of proteins work together to generate caveolae: integral membrane proteins termed caveolins and cytoplasmic coat proteins called cavins. Caveolae respond to membrane stress by releasing cavins into the cytosol. A crucial aspect of this model is tight regulation of cytosolic pools of cavin under resting conditions. We now show that a recently identified region of cavin1 that can bind phosphoinositide (PI) lipids is also a major site of ubiquitylation. Ubiquitylation of lysines within this site leads to rapid proteasomal degradation. In cells that lack caveolins and caveolae, cavin1 is cytosolic and rapidly degraded as compared with cells in which cavin1 is associated with caveolae. Membrane stretching causes caveolar disassembly, release of cavin complexes into the cytosol, and increased proteasomal degradation of wild-type cavin1 but not mutant cavin1 lacking the major ubiquitylation site. Release of cavin1 from caveolae thus leads to exposure of key lysine residues in the PI-binding region, acting as a trigger for cavin1 ubiquitylation and down-regulation. This mutually exclusive PI binding/ubiquitylation mechanism may help maintain low levels of cytosolic cavin1 in resting cells, a prerequisite for cavins acting as signaling modules following release from caveolae. PMID- 26269586 TI - The Genome Sequence of Saccharomyces eubayanus and the Domestication of Lager Brewing Yeasts. AB - The dramatic phenotypic changes that occur in organisms during domestication leave indelible imprints on their genomes. Although many domesticated plants and animals have been systematically compared with their wild genetic stocks, the molecular and genomic processes underlying fungal domestication have received less attention. Here, we present a nearly complete genome assembly for the recently described yeast species Saccharomyces eubayanus and compare it to the genomes of multiple domesticated alloploid hybrids of S. eubayanus * S. cerevisiae (S. pastorianus syn. S. carlsbergensis), which are used to brew lager style beers. We find that the S. eubayanus subgenomes of lager-brewing yeasts have experienced increased rates of evolution since hybridization, and that certain genes involved in metabolism may have been particularly affected. Interestingly, the S. eubayanus subgenome underwent an especially strong shift in selection regimes, consistent with more extensive domestication of the S. cerevisiae parent prior to hybridization. In contrast to recent proposals that lager-brewing yeasts were domesticated following a single hybridization event, the radically different neutral site divergences between the subgenomes of the two major lager yeast lineages strongly favor at least two independent origins for the S. cerevisiae * S. eubayanus hybrids that brew lager beers. Our findings demonstrate how this industrially important hybrid has been domesticated along similar evolutionary trajectories on multiple occasions. PMID- 26269587 TI - Reaction of Hydrogen Sulfide with Disulfide and Sulfenic Acid to Form the Strongly Nucleophilic Persulfide. AB - Hydrogen sulfide (H2S) is increasingly recognized to modulate physiological processes in mammals through mechanisms that are currently under scrutiny. H2S is not able to react with reduced thiols (RSH). However, H2S, more precisely HS(-), is able to react with oxidized thiol derivatives. We performed a systematic study of the reactivity of HS(-) toward symmetric low molecular weight disulfides (RSSR) and mixed albumin (HSA) disulfides. Correlations with thiol acidity and computational modeling showed that the reaction occurs through a concerted mechanism. Comparison with analogous reactions of thiolates indicated that the intrinsic reactivity of HS(-) is 1 order of magnitude lower than that of thiolates. In addition, H2S is able to react with sulfenic acids (RSOH). The rate constant of the reaction of H2S with the sulfenic acid formed in HSA was determined. Both reactions of H2S with disulfides and sulfenic acids yield persulfides (RSSH), recently identified post-translational modifications. The formation of this derivative in HSA was determined, and the rate constants of its reactions with a reporter disulfide and with peroxynitrite revealed that persulfides are better nucleophiles than thiols, which is consistent with the alpha effect. Experiments with cells in culture showed that treatment with hydrogen peroxide enhanced the formation of persulfides. Biological implications are discussed. Our results give light on the mechanisms of persulfide formation and provide quantitative evidence for the high nucleophilicity of these novel derivatives, setting the stage for understanding the contribution of the reactions of H2S with oxidized thiol derivatives to H2S effector processes. PMID- 26269588 TI - Neutrophil elastase promotes interleukin-1beta secretion from human coronary endothelium. AB - The endothelium is critically involved in the pathogenesis of atherosclerosis by producing pro-inflammatory mediators, including IL-1beta. Coronary arteries from patients with ischemic heart disease express large amounts of IL-1beta in the endothelium. However, the mechanism by which endothelial cells (ECs) release IL 1beta remains to be elucidated. We investigated neutrophil elastase (NE), a potent serine protease detected in vulnerable areas of human carotid plaques, as a potential "trigger" for IL-1beta processing and release. This study tested the hypothesis that NE potentiates the processing and release of IL-1beta from human coronary endothelium. We found that NE cleaves the pro-isoform of IL-1beta in ECs and causes significant secretion of bioactive IL-1beta via extracellular vesicles. This release was attenuated significantly by inhibition of neutrophil elastase but not caspase-1. Transient increases in intracellular Ca(2+) levels were observed prior to secretion. Inside ECs, and after NE treatment only, IL 1beta was detected within LAMP-1-positive multivesicular bodies. The released vesicles contained bioactive IL-1beta. In vivo, in experimental atherosclerosis, NE was detected in mature atherosclerotic plaques, predominantly in the endothelium, alongside IL-1beta. This study reveals a novel mechanistic link between NE expression in atherosclerotic plaques and concomitant pro-inflammatory bioactive IL-1beta secretion from ECs. This could reveal additional potential anti-IL-1beta therapeutic targets and provide further insights into the inflammatory process by which vascular disease develops. PMID- 26269589 TI - The nicotine metabolite, cotinine, alters the assembly and trafficking of a subset of nicotinic acetylcholine receptors. AB - Exposure to nicotine alters the trafficking and assembly of nicotinic receptors (nAChRs), leading to their up-regulation on the plasma membrane. Although the mechanism is not fully understood, nicotine-induced up-regulation is believed to contribute to nicotine addiction. The effect of cotinine, the primary metabolite of nicotine, on nAChR trafficking and assembly has not been extensively investigated. We utilize a pH-sensitive variant of GFP, super ecliptic pHluorin, to differentiate between intracellular nAChRs and those expressed on the plasma membrane to quantify changes resulting from cotinine and nicotine exposure. Similar to nicotine, exposure to cotinine increases the number of alpha4beta2 receptors on the plasma membrane and causes a redistribution of intracellular receptors. In contrast to this, cotinine exposure down-regulates alpha6beta2beta3 receptors. We also used single molecule fluorescence studies to show that cotinine and nicotine both alter the assembly of alpha4beta2 receptors to favor the high sensitivity (alpha4)2(beta2)3 stoichiometry. PMID- 26269590 TI - The cAMP Signaling Pathway and Direct Protein Kinase A Phosphorylation Regulate Polycystin-2 (TRPP2) Channel Function. AB - Polycystin-2 (PC2) is a TRP-type, Ca(2+)-permeable non-selective cation channel that plays an important role in Ca(2+) signaling in renal and non-renal cells. The effect(s) of the cAMP pathway and kinase mediated phosphorylation of PC2 seem to be relevant to PC2 trafficking and its interaction with polycystin-1. However, the role of PC2 phosphorylation in channel function is still poorly defined. Here we reconstituted apical membranes of term human syncytiotrophoblast (hST), containing endogenous PC2 (PC2hst), and in vitro translated channel protein (PC2iv). Addition of the catalytic subunit of PKA increased by 566% the spontaneous PC2hst channel activity in the presence of ATP. Interestingly, 8-Br cAMP also stimulated spontaneous PC2hst channel activity in the absence of the exogenous kinase. Either stimulation was inhibited by addition of alkaline phosphatase, which in turn, was reversed by the phosphatase inhibitor vanadate. Neither maneuver modified the single channel conductance but instead increased channel mean open time. PKA directly phosphorylated PC2, which increased the mean open time but not the single channel conductance of the channel. PKA phosphorylation did not modify either R742X truncated or S829A-mutant PC2iv channel function. The data indicate that the cAMP pathway regulates PC2-mediated cation transport in the hST. The relevant PKA site for PC2 channel regulation centers on a single residue serine 829, in the carboxyl terminus. PMID- 26269591 TI - Transcriptional Regulation of the Astrocytic Excitatory Amino Acid Transporter 1 (EAAT1) via NF-kappaB and Yin Yang 1 (YY1). AB - Astrocytic glutamate transporter excitatory amino acid transporter (EAAT) 1, also known as glutamate aspartate transporter (GLAST) in rodents, is one of two glial glutamate transporters that are responsible for removing excess glutamate from synaptic clefts to prevent excitotoxic neuronal death. Despite its important role in neurophysiological functions, the molecular mechanisms of EAAT1 regulation at the transcriptional level remain to be established. Here, we report that NF kappaB is a main positive transcription factor for EAAT1, supported by the following: 1) EAAT1 contains two consensus sites for NF-kappaB, 2) mutation of NF kappaB binding sites decreased EAAT1 promoter activity, and 3) activation of NF kappaB increased, whereas inhibition of NF-kappaB decreased EAAT1 promoter activity and mRNA/protein levels. EGF increased EAAT1 mRNA/protein levels and glutamate uptake via NF-kappaB. The transcription factor yin yang 1 (YY1) plays a role as a critical negative regulator of EAAT1, supported by the following: 1) the EAAT1 promoter contains multiple consensus sites for YY1, 2) overexpression of YY1 decreased EAAT1 promoter activity and mRNA/protein levels, and 3) knockdown of YY1 increased EAAT1 promoter activity and mRNA/protein levels. Manganese decreased EAAT1 expression via YY1. Epigenetic modifiers histone deacetylases (HDACs) served as co-repressors of YY1 to further decrease EAAT1 promoter activity, whereas inhibition of HDACs reversed manganese-induced decrease of EAAT1 expression. Taken together, our findings suggest that NF-kappaB is a critical positive regulator of EAAT1, mediating the stimulatory effects of EGF, whereas YY1 is a negative regulator of EAAT1 with HDACs as co-repressors, mediating the inhibitory effects of manganese on EAAT1 regulation. PMID- 26269592 TI - Signal Transduction and Intracellular Trafficking by the Interleukin 36 Receptor. AB - Improper signaling of the IL-36 receptor (IL-36R), a member of the IL-1 receptor family, has been associated with various inflammation-associated diseases. However, the requirements for IL-36R signal transduction remain poorly characterized. This work seeks to define the requirements for IL-36R signaling and intracellular trafficking. In the absence of cognate agonists, IL-36R was endocytosed and recycled to the plasma membrane. In the presence of IL-36, IL-36R increased accumulation in LAMP1+ lysosomes. Endocytosis predominantly used a clathrin-mediated pathway, and the accumulation of the IL-36R in lysosomes did not result in increased receptor turnover. The ubiquitin-binding Tollip protein contributed to IL-36R signaling and increased the accumulation of both subunits of the IL-36R. PMID- 26269593 TI - Conserved overlapping gene arrangement, restricted expression, and biochemical activities of DNA polymerase nu (POLN). AB - DNA polymerase nu (POLN) is one of 16 DNA polymerases encoded in vertebrate genomes. It is important to determine its gene expression patterns, biological roles, and biochemical activities. By quantitative analysis of mRNA expression, we found that POLN from the zebrafish Danio rerio is expressed predominantly in testis. POLN is not detectably expressed in zebrafish embryos or in mouse embryonic stem cells. Consistent with this, injection of POLN-specific morpholino antisense oligonucleotides did not interfere with zebrafish embryonic development. Analysis of transcripts revealed that vertebrate POLN has an unusual gene expression arrangement, sharing a first exon with HAUS3, the gene encoding augmin-like complex subunit 3. HAUS3 is broadly expressed in embryonic and adult tissues, in contrast to POLN. Differential expression of POLN and HAUS3 appears to arise by alternate splicing of transcripts in mammalian cells and zebrafish. When POLN was ectopically overexpressed in human cells, it specifically coimmunoprecipitated with the homologous recombination factors BRCA1 and FANCJ, but not with previously suggested interaction partners (HELQ and members of the Fanconi anemia core complex). Purified zebrafish POLN protein is capable of thymine glycol bypass and strand displacement, with activity dependent on a basic amino acid residue known to stabilize the primer-template. These properties are conserved with the human enzyme. Although the physiological function of pol nu remains to be clarified, this study uncovers distinctive aspects of its expression control and evolutionarily conserved properties of this DNA polymerase. PMID- 26269594 TI - Nucling, a novel apoptosis-associated protein, controls mammary gland involution by regulating NF-kappaB and STAT3. AB - Postpartum mammary gland involution is the physiological process by which the lactating gland returns to its pre-pregnant state. In rodent models, the microenvironment of mammary gland involution is sufficient to induce enhanced tumor cell growth, local invasion, and metastasis. Therefore, a deeper understanding of the physiological regulation of involution may provide in-depth information on breast cancer therapy. We herein identified Nucling as an important regulator of involution of the mammary gland. A knock-out mouse model was generated and revealed that postpartum involution were impaired in mice lacking Nucling. Involution is normally associated with an increase in the activation of NF-kappaB and STAT3, which is required for the organized regulation of involution, and was observed in WT glands, but not in the absence of Nucling. Furthermore, the loss of Nucling led to the suppression of Calpain-1, IL-6, and C/EBPdelta factors, which are known to be essential for normal involution. The number of M2 macrophages, which are crucial for epithelial cell death and adipocyte repopulation after weaning, was also reduced in Nucling-KO glands. Taken together, the results of the present study demonstrated that Nucling played an important role in mammary gland involution by regulating NF-kappaB and STAT3 signaling pathways. PMID- 26269595 TI - Probing the Catalytic Mechanism of Copper Amine Oxidase from Arthrobacter globiformis with Halide Ions. AB - The catalytic reaction of copper amine oxidase proceeds through a ping-pong mechanism comprising two half-reactions. In the initial half-reaction, the substrate amine reduces the Tyr-derived cofactor, topa quinone (TPQ), to an aminoresorcinol form (TPQamr) that is in equilibrium with a semiquinone radical (TPQsq) via an intramolecular electron transfer to the active-site copper. We have analyzed this reductive half-reaction in crystals of the copper amine oxidase from Arthrobacter globiformis. Anerobic soaking of the crystals with an amine substrate shifted the equilibrium toward TPQsq in an "on-copper" conformation, in which the 4-OH group ligated axially to the copper center, which was probably reduced to Cu(I). When the crystals were soaked with substrate in the presence of halide ions, which act as uncompetitive and noncompetitive inhibitors with respect to the amine substrate and dioxygen, respectively, the equilibrium in the crystals shifted toward the "off-copper" conformation of TPQamr. The halide ion was bound to the axial position of the copper center, thereby preventing TPQamr from adopting the on-copper conformation. Furthermore, transient kinetic analyses in the presence of viscogen (glycerol) revealed that only the rate constant in the step of TPQamr/TPQsq interconversion is markedly affected by the viscogen, which probably perturbs the conformational change. These findings unequivocally demonstrate that TPQ undergoes large conformational changes during the reductive half-reaction. PMID- 26269596 TI - Biased Gs versus Gq proteins and beta-arrestin signaling in the NK1 receptor determined by interactions in the water hydrogen bond network. AB - X-ray structures, molecular dynamics simulations, and mutational analysis have previously indicated that an extended water hydrogen bond network between trans membranes I-III, VI, and VII constitutes an allosteric interface essential for stabilizing different active and inactive helical constellations during the seven trans-membrane receptor activation. The neurokinin-1 receptor signals efficiently through Gq, Gs, and beta-arrestin when stimulated by substance P, but it lacks any sign of constitutive activity. In the water hydrogen bond network the neurokinin-1 has a unique Glu residue instead of the highly conserved AspII:10 (2.50). Here, we find that this GluII:10 occupies the space of a putative allosteric modulating Na(+) ion and makes direct inter-helical interactions in particular with SerIII:15 (3.39) and AsnVII:16 (7.49) of the NPXXY motif. Mutational changes in the interface between GluII:10 and AsnVII:16 created receptors that selectively signaled through the following: 1) Gq only; 2) beta arrestin only; and 3) Gq and beta-arrestin but not through Gs. Interestingly, increased constitutive Gs but not Gq signaling was observed by Ala substitution of four out of the six core polar residues of the network, in particular SerIII:15. Three residues were essential for all three signaling pathways, i.e. the water-gating micro-switch residues TrpVI:13 (6.48) of the CWXP motif and TyrVII:20 (7.53) of the NPXXY motif plus the totally conserved AsnI:18 (1.50) stabilizing the kink in trans-membrane VII. It is concluded that the interface between position II:10 (2.50), III:15 (3.39), and VII:16 (7.49) in the center of the water hydrogen bond network constitutes a focal point for fine-tuning seven trans-membrane receptor conformations activating different signal transduction pathways. PMID- 26269597 TI - ERK2-Pyruvate Kinase Axis Permits Phorbol 12-Myristate 13-Acetate-induced Megakaryocyte Differentiation in K562 Cells. AB - Metabolic changes that contribute to differentiation are not well understood. Overwhelming evidence shows the critical role of glycolytic enzyme pyruvate kinase (PK) in directing metabolism of proliferating cells. However, its role in metabolism of differentiating cells is unclear. Here we studied the role of PK in phorbol 12-myristate 13-acetate (PMA)-induced megakaryocytic differentiation in human leukemia K562 cells. We observed that PMA treatment decreased cancer-type anabolic metabolism but increased ATP production, along with up-regulated expression of two PK isoforms (PKM2 and PKR) in an ERK2-dependent manner. Interestingly, silencing of PK (PKM2 and PKR) inhibited PMA-induced megakaryocytic differentiation, as revealed by decreased expression of megakaryocytic differentiation marker CD61 and cell cycle behavior. Further, PMA induced ATP production reduced greatly upon PK silencing, suggesting that PK is required for ATP synthesis. In addition to metabolic effects, PMA treatment also translocated PKM2, but not PKR, into nucleus. ERK1/2 knockdowns independently and together suggested the role of ERK2 in the up-regulation of both the isoforms of PK, proposing a role of ERK2-PK isoform axis in differentiation. Collectively, our findings unravel ERK2 guided PK-dependent metabolic changes during PMA induction, which are important in megakaryocytic differentiation. PMID- 26269598 TI - Discovery of PPi-type Phosphoenolpyruvate Carboxykinase Genes in Eukaryotes and Bacteria. AB - Phosphoenolpyruvate carboxykinase (PEPCK) is one of the pivotal enzymes that regulates the carbon flow of the central metabolism by fixing CO2 to phosphoenolpyruvate (PEP) to produce oxaloacetate or vice versa. Whereas ATP- and GTP-type PEPCKs have been well studied, and their protein identities are established, inorganic pyrophosphate (PPi)-type PEPCK (PPi-PEPCK) is poorly characterized. Despite extensive enzymological studies, its protein identity and encoding gene remain unknown. In this study, PPi-PEPCK has been identified for the first time from a eukaryotic human parasite, Entamoeba histolytica, by conventional purification and mass spectrometric identification of the native enzyme, followed by demonstration of its enzymatic activity. A homolog of the amebic PPi-PEPCK from an anaerobic bacterium Propionibacterium freudenreichii subsp. shermanii also exhibited PPi-PEPCK activity. The primary structure of PPi PEPCK has no similarity to the functional homologs ATP/GTP-PEPCKs and PEP carboxylase, strongly suggesting that PPi-PEPCK arose independently from the other functional homologues and very likely has unique catalytic sites. PPi-PEPCK homologs were found in a variety of bacteria and some eukaryotes but not in archaea. The molecular identification of this long forgotten enzyme shows us the diversity and functional redundancy of enzymes involved in the central metabolism and can help us to understand the central metabolism more deeply. PMID- 26269599 TI - Structure-Functional Characterization of Cytochrome P450 Sterol 14alpha Demethylase (CYP51B) from Aspergillus fumigatus and Molecular Basis for the Development of Antifungal Drugs. AB - Aspergillus fumigatus is the opportunistic fungal pathogen that predominantly affects the immunocompromised population and causes 600,000 deaths/year. The cytochrome P450 51 (CYP51) inhibitor voriconazole is currently the drug of choice, yet the treatment efficiency remains low, calling for rational development of more efficient agents. A. fumigatus has two CYP51 genes, CYP51A and CYP51B, which share 59% amino acid sequence identity. CYP51B is expressed constitutively, whereas gene CYP51A is reported to be inducible. We expressed, purified, and characterized A. fumigatus CYP51B, including determination of its substrate preferences, catalytic parameters, inhibition, and x-ray structure in complexes with voriconazole and the experimental inhibitor (R)-N-(1-(2,4 dichlorophenyl)-2-(1H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2 yl)benzamide (VNI). The enzyme demethylated its natural substrate eburicol and the plant CYP51 substrate obtusifoliol at steady-state rates of 17 and 16 min( 1), respectively, but did not metabolize lanosterol, and the topical antifungal drug miconazole was the strongest inhibitor that we identified. The x-ray crystal structures displayed high overall similarity of A. fumigatus CYP51B to CYP51 orthologs from other biological kingdoms but revealed phylum-specific differences relevant to enzyme catalysis and inhibition. The complex with voriconazole provides an explanation for the potency of this relatively small molecule, whereas the complex with VNI outlines a direction for further enhancement of the efficiency of this new inhibitory scaffold to treat humans afflicted with filamentous fungal infections. PMID- 26269600 TI - Modulator of apoptosis 1 (MOAP-1) is a tumor suppressor protein linked to the RASSF1A protein. AB - Modulator of apoptosis 1 (MOAP-1) is a BH3-like protein that plays key roles in cell death or apoptosis. It is an integral partner to the tumor suppressor protein, Ras association domain family 1A (RASSF1A), and functions to activate the Bcl-2 family pro-apoptotic protein Bax. Although RASSF1A is now considered a bona fide tumor suppressor protein, the role of MOAP-1 as a tumor suppressor protein has yet to be determined. In this study, we present several lines of evidence from cancer databases, immunoblotting of cancer cells, proliferation, and xenograft assays as well as DNA microarray analysis to demonstrate the role of MOAP-1 as a tumor suppressor protein. Frequent loss of MOAP-1 expression, in at least some cancers, appears to be attributed to mRNA down-regulation and the rapid proteasomal degradation of MOAP-1 that could be reversed utilizing the proteasome inhibitor MG132. Overexpression of MOAP-1 in several cancer cell lines resulted in reduced tumorigenesis and up-regulation of genes involved in cancer regulatory pathways that include apoptosis (p53, Fas, and MST1), DNA damage control (poly(ADP)-ribose polymerase and ataxia telangiectasia mutated), those within the cell metabolism (IR-alpha, IR-beta, and AMP-activated protein kinase), and a stabilizing effect on microtubules. The loss of RASSF1A (an upstream regulator of MOAP-1) is one of the earliest detectable epigenetically silenced tumor suppressor proteins in cancer, and we speculate that the additional loss of function of MOAP-1 may be a second hit to functionally compromise the RASSF1A/MOAP-1 death receptor-dependent pathway and drive tumorigenesis. PMID- 26269601 TI - Fibroblast-derived neuregulin 1 promotes compensatory ErbB3 receptor signaling in mutant BRAF melanoma. AB - Rapidly accelerated fibrosarcoma (RAF) inhibitors are first-line treatments for patients harboring V600E/K mutant BRAF melanoma. Although RAF inhibitors produce high response rates, the degree of tumor regression is heterogeneous. Compensatory/adaptive responses to targeted inhibitors are frequently initiated by the activation of growth factor receptor tyrosine kinases, including ErbB3, and factors from the tumor microenvironment may play an important role. We have shown previously that mutant v-raf murine sarcoma viral oncogene homolog B1 (BRAF) melanoma cells have enhanced activation of ErbB3 following RAF inhibition. However, the source of neuregulin 1 (NRG1), the ligand for ErbB3, is unknown. In this study, we demonstrate that NRG1 is highly expressed by dermal fibroblasts and cancer-associated fibroblasts (CAFs) isolated from mutant BRAF melanomas. Conditioned medium from fibroblasts and CAFs enhanced ErbB3 pathway activation and limited RAF inhibitor cytotoxicity in V600 mutant BRAF-harboring melanomas. Targeting the ErbB3/ErbB2 pathway partially reversed the protective effects of fibroblast/CAF-derived NRG1 on cell growth properties of RAF inhibitor-treated melanoma cells. These findings support the idea that NRG1, acting in a paracrine manner, promotes resistance to RAF inhibitors and emphasize that targeting the ErbB3/ErbB2 pathway will likely improve the efficacy of RAF inhibitors for mutant BRAF melanoma patients. PMID- 26269602 TI - Polymorphic Variants of Human Rhodanese Exhibit Differences in Thermal Stability and Sulfur Transfer Kinetics. AB - Rhodanese is a component of the mitochondrial H2S oxidation pathway. Rhodanese catalyzes the transfer of sulfane sulfur from glutathione persulfide (GSSH) to sulfite generating thiosulfate and from thiosulfate to cyanide generating thiocyanate. Two polymorphic variations have been identified in the rhodanese coding sequence in the French Caucasian population. The first, 306A->C, has an allelic frequency of 1% and results in an E102D substitution in the encoded protein. The second polymorphism, 853C->G, has an allelic frequency of 5% and leads to a P285A substitution. In this study, we have examined differences in the stability between wild-type rhodanese and the E102D and P285A variants and in the kinetics of the sulfur transfer reactions. The Asp-102 and Ala-285 variants are more stable than wild-type rhodanese and exhibit kcat/Km,CN values that are 17- and 1.6-fold higher, respectively. All three rhodanese forms preferentially catalyze sulfur transfer from GSSH to sulfite, generating thiosulfate and glutathione. The kcat/Km,sulfite values for the variants in the sulfur transfer reaction from GSSH to sulfite were 1.6- (Asp-102) and 4-fold (Ala-285) lower than for wild-type rhodanese, whereas the kcat/Km,GSSH values were similar for all three enzymes. Thiosulfate-dependent H2S production in murine liver lysate is low, consistent with a role for rhodanese in sulfide oxidation. Our studies show that polymorphic variations that are distant from the active site differentially modulate the sulfurtransferase activity of human rhodanese to cyanide versus sulfite and might be important in differences in susceptibility to diseases where rhodanese dysfunction has been implicated, e.g. inflammatory bowel diseases. PMID- 26269603 TI - Improvement of Stability and Efficacy of C16Y Therapeutic Peptide via Molecular Self-Assembly into Tumor-Responsive Nanoformulation. AB - Peptide therapeutics hold great promise for the treatment of cancer due to low toxicity, high specificity, and ease of synthesis and modification. However, the unfavorable pharmacokinetic parameters strictly limit their therapeutic efficacy and clinical translation. Here, we tailor-designed an amphiphilic chimeric peptide through conjugation of functional 3-diethylaminopropyl isothiocyanate (DEAP) molecules to a short antitumor peptide, C16Y. The ultimate DEAP-C16Y peptides self-assembled into spherical nanostructures at physiologic conditions, which dissociated to release individual peptide molecules in weakly acidic tumors. DEAP-C16Y peptides showed negligible cytotoxicity but impaired vascular endothelial cell migration and tubule formation by inactivation of the focal adhesion kinase and PI3K-Akt pathways, as well as tumor cell invasion by decreasing invadopodia formation. Compared with C16Y, the systemically administered DEAP-C16Y nanostructures exhibited superior stability, thereby allowing prolonged treatment interval and resulting in significant decreases in microvessel density, tumor growth, and distant metastasis formation in orthotopic mammary tumor models. Through encapsulation of hydrophobic doxorubicin, DEAP-C16Y nanostructure served as a smart carrier to achieve targeted drug delivery and combination therapy. Our study, for the first time, demonstrates that a simple nanoformulation using a functional antitumor peptide as the building block can show innate antitumor activity and also provide a nanoplatform for combination therapy, opening a new avenue for the design of antitumor nanotherapeutics. PMID- 26269604 TI - Anticancer Properties of a Novel Class of Tetrafluorinated Thalidomide Analogues. AB - Thalidomide has demonstrated clinical activity in various malignancies affecting immunomodulatory and angiogenic pathways. The development of novel thalidomide analogs with improved efficacy and decreased toxicity is an ongoing research effort. We recently designed and synthesized a new class of compounds, consisting of both tetrafluorinated thalidomide analogues (Gu973 and Gu998) and tetrafluorobenzamides (Gu1029 and Gu992). In this study, we demonstrate the antiangiogenic properties of these newly synthesized compounds. We examined the specific antiangiogenic characteristics in vitro using rat aortic rings with carboxyamidotriazole as a positive control. In addition, further in vitro efficacy was evaluated using human umbilical vein endothelial cells (HUVEC) and PC3 cells treated with 5 and 10 MUmol/L doses of each compound. All compounds were seen to reduce microvessel outgrowth in rat aortic rings as well as to inhibit HUVECs to a greater extent, at lower concentrations than previously tested thalidomide analogs. The antiangiogenic properties of the compounds were also examined in vivo in fli1:EGFP zebrafish embryos, where all compounds were seen to inhibit the extent of outgrowth of newly developing blood vessels. In addition, Gu1029 and Gu973 reduced the anti-inflammatory response in mpo:GFP zebrafish embryos, whereas Gu998 and Gu992 showed no difference. The compounds' antitumor effects were also explored in vivo using the human prostate cancer PC3 xenograft model. All four compounds were also screened in vivo in chicken embryos to investigate their teratogenic potential. This study establishes these novel thalidomide analogues as a promising immunomodulatory class with anticancer effects that warrant further development to characterize their mechanisms of action. PMID- 26269606 TI - Redesigning a Monospecific Anti-FGFR3 Antibody to Add Selectivity for FGFR2 and Expand Antitumor Activity. AB - FGF receptors (FGFR) are attractive candidate targets for cancer therapy because they are dysregulated in several human malignancies. FGFR2 and FGFR3 can be inhibited potentially without disrupting adult tissue homeostasis. In contrast, blocking the closely related FGFR1 and FGFR4, which regulate specific metabolic functions, carries a greater safety risk. An anti-FGFR3 antibody was redesigned here to create function-blocking antibodies that bind with dual specificity to FGFR3 and FGFR2 but spare FGFR1 and FGFR4. R3Mab, a previously developed monospecific anti-FGFR3 antibody, was modified via structure-guided phage display and acquired additional binding to FGFR2. The initial variant was trispecific, binding tightly to FGFR3 and FGFR2 and moderately to FGFR4, while sparing FGFR1. The X-ray crystallographic structure indicated that the antibody variant was bound to a similar epitope on FGFR2 as R3Mab on FGFR3. The antibody was further engineered to decrease FGFR4-binding affinity while retaining affinity for FGFR3 and FGFR2. The resulting dual-specific antibodies blocked FGF binding to FGFR3 and FGFR2 and inhibited downstream signaling. Moreover, they displayed efficacy in mice against human tumor xenografts overexpressing FGFR3 or FGFR2. Thus, a monospecific antibody can be exquisitely tailored to confer or remove binding to closely related targets to expand and refine therapeutic potential. PMID- 26269605 TI - CXCR4 Protein Epitope Mimetic Antagonist POL5551 Disrupts Metastasis and Enhances Chemotherapy Effect in Triple-Negative Breast Cancer. AB - The SDF-1 receptor CXCR4 has been associated with early metastasis and poorer prognosis in breast cancers, especially the most aggressive triple-negative subtype. In line with previous reports, we found that tumoral CXCR4 expression in patients with locally advanced breast cancer was associated with increased metastases and rapid tumor progression. Moreover, high CXCR4 expression identified a group of bone marrow-disseminated tumor cells (DTC)-negative patients at high risk for metastasis and death. The protein epitope mimetic (PEM) POL5551, a novel CXCR4 antagonist, inhibited binding of SDF-1 to CXCR4, had no direct effects on tumor cell viability, but reduced migration of breast cancer cells in vitro. In two orthotopic models of triple-negative breast cancer, POL5551 had little inhibitory effect on primary tumor growth, but significantly reduced distant metastasis. When combined with eribulin, a chemotherapeutic microtubule inhibitor, POL5551 additively reduced metastasis and prolonged survival in mice after resection of the primary tumor compared with single-agent eribulin. Hypothesizing that POL5551 may mobilize tumor cells from their microenvironment and sensitize them to chemotherapy, we used a "chemotherapy framing" dosing strategy. When administered shortly before and after eribulin treatment, three doses of POL5551 with eribulin reduced bone and liver tumor burden more effectively than chemotherapy alone. These data suggest that sequenced administration of CXCR4 antagonists with cytotoxic chemotherapy synergize to reduce distant metastases. PMID- 26269607 TI - Clustering of Cancer Cell Lines Using A Promoter- Targeted Liquid Hybridization Capture-Based Bisulfite Sequencing Approach. AB - DNA methylation plays a significant role in assuring cell identity, thus potentiating its application in molecular classification of cancers in respect to tissue-origins or clinically and etiologically distinct subtypes. In this study, we optimized our liquid hybridization capture-based bisulfite sequencing (LHC-BS) approach on the gene promoter regions of 11 cell lines. Our results indicated that promoter methylomes could not only cluster cancer cell lines with respect to tissue origins but also differentiate cancer subtypes based on CpG island methylator phenotype (CIMP). Promoter-targeted LHC-BS as means for comprehensive screening and classifying cancer cells with promoter methylomes provided a powerful strategy for further complex clinical studies. PMID- 26269608 TI - Impact of the Intra- and Inter-observer Variability in the Delineation of Parotid Glands on the Dose Calculation During Head and Neck Helical Tomotherapy. AB - The intra- and inter-observer variability in delineation of the parotids on the kilo-voltage computed tomography (kVCT) and mega-voltage computed tomography (MVCT) were examined to establish their impact on the dose calculation during adaptive head and neck helical tomotherapy (HT). Three observers delineated left and right parotids for ten randomly selected patients with oropharynx cancer treated on HT. The pre-treatment kVCT and the MVCT from the first fraction of irradiation were selected to delineation. The delineation procedure was repeated three times by each observer. The parotids were delineated according to the institutional protocol. The analyses included intra-observer reproducibility and inter-structure, -observer and -modality variability of the volume and dose. The differences between the left and right parotid outlines were not statistically significant (p > 0.3). The reproducibility of the delineation was confirmed for each observer on the kVCT (p > 0.2) and on the MVCT (p > 0.1). The inter-observer variability of the outlines was significant (p < 0.001) as well as the inter modality variability (p < 0.006). The parotids delineated on the MVCT were 10% smaller than on the kVCT. The inter-observer variability of the parotids delineation did not affect the average dose (p = 0.096 on the kVCT and p = 0.176 on the MVCT). The dose calculated on the MVCT was higher by 3.3% than dose from the kVCT (p = 0.009). Usage of the institutional protocols for the parotids delineation reduces intra-observer variability and increases reproducibility of the outlines. These protocols do not eliminate delineation differences between the observers, but these differences are not clinically significant and do not affect average doses in the parotids. The volumes of the parotids delineated on the MVCT are smaller than on the kVCT, which affects the differences in the calculated doses. PMID- 26269609 TI - A Feasibility Study of a Tilted Head Position in Helical Tomotherapy for Fractionated Stereotactic Radiotherapy of Intracranial Malignancies. AB - Herein, we evaluated the feasibility of placing patients in a tilted head position as part of routine clinical practice for fractionated stereotactic radiotherapy (FSRT) of intracranial tumors using helical tomotherapy (HT), by assessing its dosimetric benefit and setup accuracy. We reviewed treatment plans of four cases that were to receive FSRT for brain lesions in normal and head tilted positions. These patients underwent two computed tomography (CT) scans: first in the normal supine position and then in the supine position with the head tilted at a 458 angle. Two separate HT plans for each position were generated in these four patients, using the same planning parameters. Plans were compared for target conformity and dose homogeneity. Maximum and average doses to critical organs, including normal brain, brain stem, optic chiasm, optic nerves, and the eyes, were considered. To evaluate setup accuracy, patient movement during treatment was assessed by post-treatment megavoltage CT scans. Both HT plans achieved similar conformal and homogeneous dose coverage to the target. Head tilted HT delivered lower average and maximum doses to critical organs in the cases where the tumor was located on the same plane with critical organs, particularly when they were not directly attached. Placement in the head-tilted position without a mouthpiece allowed for increased patient movement during treatment, while use of a mouthpiece reduced patient movement to even less than that observed for normal setup in the supine position. This pilot study showed that placement in a tilted head position for FSRT of intracranial tumors using HT may be of clinical use, but depends on the tumor location. PMID- 26269610 TI - Identical Quality Assurance for Volumetric Modulated Arc Therapy in Elekta and Varian Machines. AB - Volumetric modulated arc therapy (VMAT) has been adopted by many clinics for its higher delivery efficiency compared to conventional intensity modulated radiotherapy techniques. Currently, the quality assurance (QA) has remained a challenge in that no identical tests are available for accelerators from different vendors. This study is the first attempt to design identical QA tests for the VMAT technique for Varian and Elekta machines. Identical procedures testing MLC positions and movements, dose rate variations, and gantry positions and movement were created for both machines. These included picket fence (PF), dose rate vs. gantry speed (DRGS) and MLC speed vs. dose rate (MLCDR) tests. Deliverable plans for these tests were made with in-house software that was deliverable for linacs from two vendors (Elekta Synergy and Varian Trilogy). The electronic portal imaging device (EPID) was used for these tests. An automated analysis method was established and software was created to quantitatively evaluate the result. The systematic gap position and width errors from PF tests were within 0.5 mm. We evaluated the detectability of this program for introduced errors down to 0.2 mm. Linear relationships existed between the introduced errors and measured errors. In the DRGS test, 99.8% and 100.0% of the intensity deviations from expected profiles were less than 3% for the Synergy and Trilogy, respectively. For the MLCDR, the intensity deviations from expected profiles less than 3% were 100.0% for Synergy and 98.1% for Trilogy. Identical test series were created and implemented for VMAT accelerators from two vendors. Test results were reported from both accelerators. Comparable results were obtained from both vendors, enabling uniform criteria to be established for VMAT quality assurance. PMID- 26269611 TI - Cranio Spinal Irradiation of Medulloblastoma Using High Precision Techniques - A Dosimetric Comparison. AB - Radiotherapy planning, delivery and junction dose verification remain exigent for Cranio Spinal Irradiation (CSI) in medulloblastoma patients. This study aims to evaluate high precision techniques such as Intensity Modulated Radiation Therapy (IMRT), Rapid Arc Therapy (RA) with and without flattening filter (FF) on the basis of dosimetric analysis. Five patients treated with jagged junction Intensity Modulated RadioTherapy (IMRT) using dynamic Multi Leaf Collimators (MLC) were randomly selected for this retrospective study. IMRT, Rapid Arc (RA) plans were simulated in the same CT data set with and without flattening filter. Total dose prescribed was 28.80 Gy in 16 fractions. An evaluation criterion of 98% of PTV receiving 100% of the prescription dose was followed in all plans. Twenty treatment plans with 260 Dose Volume Histograms (DVHs) was created. Dosimetric parameters such as Dmax, Dmin, Dmean, V95%, V107%, CI for PTV and Dmax, Dmean, V80%, V50%, V30%, V10% for Organs At Risk (OAR) were extracted from DVHs. Treatment delivery efficiency was also evaluated for total Beam On Time (BOT). FFF Rapid Arc therapy : 6F_RA) resulted in conformal doses throughout the cranio spinal axis. FF and FFF dynamic IMRT had minimal V107%, 1.23% and 2.88% compared to 49.15 and 66.36 of rapid arc therapy (with and without FF). 6F_IMRT resulted in lesser mean doses to eyes, liver, lungs and kidneys. Heart mean dose was less (3.08 Gy) with 6X_IMRT. Thyroid and esophagus doses could be reduced to about 41.2% and 10% respectively with 6F_RA. The BOT for the treatment techniques were 3.43 min (6X_IMRT), 1.59 min (6F_IMRT), 5min (6X_RA), 4.5 min (6F_RA). Removal of flattening filter in IMRT could improve dose coverage along the caniospinal axis and normal tissue sparing. A reduction of 46.3% BOT could increase treatment efficiency of 6F_IMRT compared to 6X_IMRT. CSI could be simpler since junction doses can be evaded in IMRT and RA techniques. PMID- 26269612 TI - Non Tumor Perfusion Changes Following Stereotactic Radiosurgery to Brain Metastases. AB - PURPOSE: To evaluate early perfusion changes in normal tissue following stereotactic radiosurgery (SRS). METHODS: Nineteen patients harboring twenty-two brain metastases treated with SRS were imaged with dynamic susceptibility magnetic resonance imaging (DSC MRI) at baseline, 1 week and 1 month post SRS. Relative cerebral blood volume and flow (rCBV and rCBF) ratios were evaluated outside of tumor within a combined region of interest (ROI) and separately within gray matter (GM) and white matter (WM) ROIs. Three-dimensional dose distribution from each SRS plan was divided into six regions: (1) <2 Gy; (2) 2-5 Gy; (3) 5-10 Gy; (4) 10-12 Gy; (5) 12-16 Gy; and (6) >16 Gy. rCBV and rCBF ratio differences between baseline, 1 week and 1 month were compared. Best linear fit plots quantified normal tissue dose-dependency. RESULTS: Significant rCBV ratio increases were present between baseline and 1 month for all ROIs and dose ranges except for WM ROI receiving <2 Gy. rCBV ratio for all ROIs was maximally increased from baseline to 1 month with the greatest changes occurring within the 5-10 Gy dose range (53.1%). rCBF ratio was maximally increased from baseline to 1 month for all ROIs within the 5-10 Gy dose range (33.9-45.0%). Both rCBV and rCBF ratios were most elevated within GM ROIs. A weak, positive but not significant association between dose, rCBV and rCBF ratio was demonstrated. Progressive rCBV and rCBF ratio increased with dose up to 10 Gy at 1 month. CONCLUSION: Normal tissue response following SRS can be characterized by dose, tissue, and time specific increases in rCBV and rCBF ratio. PMID- 26269613 TI - Anterior Microsurgical Approach to Ventral Lower Cervical Spine Meningiomas: Indications, Surgical Technique and Long Term Outcome. AB - Ventral lower cervical spinal meningiomas with posterior displacement of the spinal cord are rare and anterior approach has been rarely reported in the literature. The authors present their experience about eight patients operated through anterior microsurgical approach. Exposure of meningiomas was achieved through one or two corpectomies, according to meningioma extension. Tumour removal was performed thanks to the aid of a dedicated ultrasonic aspirator, and intraoperative evoked potentials were employed. Particular care was taken with the materials adopted for reconstruction of the anterior dural plane, to avoid postoperative cerebrospinal fluid leak. Vertebral fusion and stabilization were achieved by tantalum cage or titanium graft in case of one or two corpectomies respectively; anterior titanium plate fixed with screws was applied in all patients. Extent of tumour removal was related to the presence of a conserved arachnoidal plane between the tumour and the spinal cord: total removal was achieved in 2 patients, while gross total removal in the other six ones. Postoperative neurological outcome, which was favourable in all patients, was related mostly to preoperative neurologic status. No recurrence after total removal and no remnant growth after gross total removal occurred during an average follow-up period of 6, 7 years. PMID- 26269614 TI - Regulatory Forum Opinion Piece*: The Value of Publishing Negative Scientific Study Data. AB - Historically it has been easier to publish positive scientific results than negative data not supporting the research hypothesis. This appears to be increasing, with fewer negative studies appearing in the literature across many disciplines. Failure to recognize the value of negative results has important implications for the toxicology community. Implications include perpetuating scientific fields based upon selective or occasionally erroneous, positive results. One example is decreased vaccination rates and increased measles infections that can lead to childhood mortality following one erroneous positive study linking vaccination to adverse effects despite multiple negative studies. Publication of negative data that challenges existing paradigms enhances progress by stopping further investment in scientifically barren topics, decreases the use of animals, and focuses research in more fruitful areas. The National Toxicology Program (NTP) publishes both positive and negative rodent data. Retrospective analysis of the NTP database has provided insights on the carcinogenic process and in the gradual acceptance of using fewer animals in safety studies. This article proposes that careful publication of both positive and negative data can enhance product safety assessment, add robustness to safety determinations in the regulatory decision-making process, and should be actively encouraged by those determining journal editorial policy. PMID- 26269615 TI - An Investigative Study of Pancreatic Exocrine Biomarkers, Histology, and Histomorphometry in Male Zucker Diabetic Fatty (ZDF) Rats Given Dulaglutide by Subcutaneous Injection Twice Weekly for 13 Weeks. AB - Glucagon-like peptide-1 (GLP-1) receptor agonist therapy has been implicated as a possible risk factor for acute pancreatitis in patients with type 2 diabetes. Dulaglutide is a long-acting GLP-1 receptor agonist in development for treatment of type 2 diabetes. The effects of dulaglutide were evaluated in male Zucker diabetic fatty (ZDF) rats to examine whether dulaglutide may induce or modulate pancreatitis. Rats were randomized to dose groups receiving twice-weekly subcutaneously administered dulaglutide 0.5, 1.5, and 5.0 mg/kg/dose (corresponding human plasma exposures following twice-weekly dosing are 3-, 8-, and 30-fold, respectively) for 13 weeks or to vehicle control. Following termination, serially trimmed sections of pancreases were stained with hematoxylin and eosin or co-stained with an epithelial marker and a marker of either proliferation or apoptosis. Efficacious reductions in glucose and hemoglobin A1c occurred at all dulaglutide doses. Lipase activity was unaffected, and there were modest increases in total and pancreatic amylase activities at all doses without individual microscopic inflammatory correlates. Microscopic dulaglutide-related pancreatic changes included increased interlobular ductal epithelium without ductal cell proliferation (>=0.5 mg/kg), increased acinar atrophy with/without inflammation (>=1.5 mg/kg), and increased incidence/severity of neutrophilic acinar pancreatic inflammation (5.0 mg/kg). In summary, dulaglutide treatment was associated with mild alterations in ductal epithelium and modest exacerbation of spontaneous lesions of the exocrine pancreas typically found in the ZDF rat model. PMID- 26269616 TI - Comparison between Flow Cytometry, Microscopy, and Lactate Dehydrogenase-Based Enzyme-Linked Immunosorbent Assay for Plasmodium falciparum Drug Susceptibility Testing under Field Conditions. AB - Flow cytometry is an objective method for conducting in vitro antimalarial sensitivity assays with increasing potential for application in field sites. We examined in vitro susceptibility to seven anti-malarial drugs for 40 fresh P. falciparum field isolates via a flow cytometry method (FCM), a colorimetric LDH based ELISA : DELI), and standard microscopic slide analysis of growth. For FCM, 184/280 (66%) assays met analytical acceptance criteria, compared to 166/280 (59%) for DELI. There was good agreement between FCM and microscopy, while DELI tended to produce higher half-maximal inhibition constants (IC50s) than FCM, with an overall bias of 2.2-fold (Bland-Altman comparison). Values for artesunate and dihydroartemisinin were most affected. Paradoxical increases in signal at very high concentrations of mefloquine and related compounds were more marked with the DELI assay, suggesting that off-target effects on LDH production may be responsible. Loss of FCM signal due to reinvasion or slow growth was observed in a small number of samples. These results extend previous work on use of flow cytometry to determine antimalarial susceptibility in terms of the number of samples, range of drugs, and comparison with other methods. PMID- 26269617 TI - Identification of Nocardia Species by Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry. AB - Matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of Nocardia species remains challenging. By identifying 83.1% (64 of 77) and 80% (8 of 10) to the species and complex levels, respectively, and 94.3% (82 of 87) to the genus level, we show that an approach using routine sample preparation, an up-to-date commercial database minimally augmented with custom spectra, and testing at an early stage of growth is promising. PMID- 26269618 TI - Persistent Infection by a Mycobacterium tuberculosis Strain That Was Theorized To Have Advantageous Properties, as It Was Responsible for a Massive Outbreak. AB - The strains involved in tuberculosis outbreaks are considered highly virulent and transmissible. We analyzed the case of a patient in Madrid, Spain, who was persistently infected over an 8-year period by the same Beijing Mycobacterium tuberculosis strain. The strain was responsible for a severe outbreak on Gran Canaria Island. The case provides us with a unique opportunity to challenge our assumptions about M. tuberculosis Beijing strains. No clinical/radiological findings consistent with a virulent strain were documented, and the in vitro growth rate of the strain in macrophages was only moderate. No secondary cases stemming from this prolonged active case were detected in the host population. The strain did not acquire resistance mutations, despite constant treatment interruptions, and it remained extremely stable, as demonstrated by the lack of single-nucleotide-polymorphism (SNP)-based differences between the sequential isolates. Our data suggest that the general assumption about M. tuberculosis Beijing strains having advantageous properties (in terms of virulence, transmissibility, and the tendency to acquire mutations and resistance) is not always accurate. PMID- 26269619 TI - New Real-Time PCR Assays for Detection of Inducible and Acquired Clarithromycin Resistance in the Mycobacterium abscessus Group. AB - Members of the Mycobacterium abscessus group (MAG) cause lung, soft tissue, and disseminated infections. The oral macrolides clarithromycin and azithromycin are commonly used for treatment. MAG can display clarithromycin resistance through the inducible erm(41) gene or via acquired mutations in the rrl (23S rRNA) gene. Strains harboring a truncation or a T28C substitution in erm(41) lose the inducible resistance trait. Phenotypic detection of clarithromycin resistance requires extended incubation (14 days), highlighting the need for faster methods to detect resistance. Two real-time PCR-based assays were developed to assess inducible and acquired clarithromycin resistance and tested on a total of 90 clinical and reference strains. A SYBR green assay was designed to distinguish between a full-length and truncated erm(41) gene by temperature shift in melting curve analysis. Single nucleotide polymorphism (SNP) allele discrimination assays were developed to distinguish T or C at position 28 of erm(41) and 23S rRNA rrl gene mutations at position 2058 and/or 2059. Truncated and full-size erm(41) genes were detected in 21/90 and 69/90 strains, respectively, with 64/69 displaying T at nucleotide position 28 and 5/69 containing C at that position. Fifteen isolates showed rrl mutations conferring clarithromycin resistance, including A2058G (11 isolates), A2058C (3 isolates), and A2059G (1 isolate). Targeted sequencing and phenotypic assessment of resistance concurred with molecular assay results. Interestingly, we also noted cooccurring strains harboring an active erm(41), inactive erm(41), and/or acquired mutational resistance, as well as slowly growing MAG strains and also strains displaying an inducible resistance phenotype within 5 days, long before the recommended 14-day extended incubation. PMID- 26269620 TI - An Echinococcus multilocularis Antigen B3 Proteoform That Shows Specific Antibody Responses to Active-Stage Alveolar Echinococcosis. AB - Alveolar echinococcosis (AE), caused by the Echinococcus multilocularis metacestode, represents one of the most frequently fatal zoonoses. Early diagnosis significantly reduces morbidity and mortality associated with AE. Diagnosis of AE largely depends on a combination of imaging and serological tests due to its minimal clinical manifestations. Several antigens derived from the whole worm and protoscolex have been targeted for AE serodiagnosis, while the antigenic properties of E. multilocularis hydatid fluid (EmHF) are unclear. We observed two AE-specific 6- and 8-kDa antigen proteoforms through an immunoproteome array of the EmHF. We identified these proteins as representing an E. multilocularis antigen B3 (EmAgB3) isoform, and the proteins were shown to be encoded by the same gene. We cloned the gene and expressed the recombinant EmAgB3 protein (rEmAgB3) in Escherichia coli. rEmAgB3 exhibited sensitivity of 90.9% (80/88 cases) and specificity of 98.5% (597/606 samples) by immunoblotting. The positive and negative predictive values were 89.9% and 98.6%, respectively. The protein did not show antibody responses to 33 AE sera collected during posttreatment follow-up monitoring. Mouse sera experimentally infected with AE protoscoleces began to demonstrate specific antibody responses to native and recombinant EmAgB3 6 months after infection. At that stage, fully mature metacestode vesicles that harbored the brood capsule, primary cell, and protoscolex were observed within an AE mass(es). The response declined along with worm degeneration. Our results demonstrate that the immune responses to this EmAgB3 isoform were highly correlated with worm viability accompanied with AE progression. rEmAgB3 is a promising biomarker for serological assessment of AE patients. PMID- 26269621 TI - Capsule Switching and Antimicrobial Resistance Acquired during Repeated Streptococcus pneumoniae Pneumonia Episodes. AB - Streptococcus pneumoniae colonizes the nasopharyngeal mucus in healthy people and causes otitis media, pneumonia, bacteremia, and meningitis. In this study, we analyzed an S. pneumoniae strain that caused 7 repeated pneumonia episodes in an 80-month-old patient with cerebral palsy during a period of 25 months. A total of 10 S. pneumoniae strains were obtained from sputum samples, and serotype 6B was isolated from samples from the first 5 episodes, whereas serotype 6A was isolated from samples from the last 2. Whole-genome sequencing showed clonality of the 10 isolates with 10 single nucleotide polymorphisms (SNPs) in the genomes. Among these SNPs, one single point mutation in the wciP gene was presumed to relate to the serotype switching from 6B to 6A, and the other mutations in parC and gyrA were related to fluoroquinolone resistance. These results suggested that an S. pneumoniae strain, which asymptomatically colonized the patient's nasopharynx or was horizontally transmitted from an asymptomatic carrier, caused the repeated pneumonia events. Phenotypic variations in the capsule type and antimicrobial susceptibility occurred during the carrier state. Hyporesponsiveness to serotypes 6B and 6A of S. pneumoniae was found even after vaccination with the 7-valent pneumococcal conjugate vaccine and the 23-valent pneumococcal polysaccharide vaccine. After an additional vaccination with the 13-valent pneumococcal conjugate vaccine, opsonic activities for both serotypes 6A and 6B significantly increased and are expected to prevent relapse by the same strain. PMID- 26269622 TI - Commutability of the First World Health Organization International Standard for Human Cytomegalovirus. AB - Quantitative detection of cytomegalovirus (CMV) DNA has become a standard part of care for many groups of immunocompromised patients; recent development of the first WHO international standard for human CMV DNA has raised hopes of reducing interlaboratory variability of results. Commutability of reference material has been shown to be necessary if such material is to reduce variability among laboratories. Here we evaluated the commutability of the WHO standard using 10 different real-time quantitative CMV PCR assays run by eight different laboratories. Test panels, including aliquots of 50 patient samples (40 positive samples and 10 negative samples) and lyophilized CMV standard, were run, with each testing center using its own quantitative calibrators, reagents, and nucleic acid extraction methods. Commutability was assessed both on a pairwise basis and over the entire group of assays, using linear regression and correspondence analyses. Commutability of the WHO material differed among the tests that were evaluated, and these differences appeared to vary depending on the method of statistical analysis used and the cohort of assays included in the analysis. Depending on the methodology used, the WHO material showed poor or absent commutability with up to 50% of assays. Determination of commutability may require a multifaceted approach; the lack of commutability seen when using the WHO standard with several of the assays here suggests that further work is needed to bring us toward true consensus. PMID- 26269623 TI - Characterization of Foodborne Outbreaks of Salmonella enterica Serovar Enteritidis with Whole-Genome Sequencing Single Nucleotide Polymorphism-Based Analysis for Surveillance and Outbreak Detection. AB - Salmonella enterica serovar Enteritidis is a significant cause of gastrointestinal illness in the United States; however, current molecular subtyping methods lack resolution for this highly clonal serovar. Advances in next-generation sequencing technologies have made it possible to examine whole genome sequencing (WGS) as a potential molecular subtyping tool for outbreak detection and source trace back. Here, we conducted a retrospective analysis of S. Enteritidis isolates from seven epidemiologically confirmed foodborne outbreaks and sporadic isolates (not epidemiologically linked) to determine the utility of WGS to identify outbreaks. A collection of 55 epidemiologically characterized clinical and environmental S. Enteritidis isolates were sequenced. Single nucleotide polymorphism (SNP)-based cluster analysis of the S. Enteritidis genomes revealed well supported clades, with less than four-SNP pairwise diversity, that were concordant with epidemiologically defined outbreaks. Sporadic isolates were an average of 42.5 SNPs distant from the outbreak clusters. Isolates collected from the same patient over several weeks differed by only two SNPs. Our findings show that WGS provided greater resolution between outbreak, sporadic, and suspect isolates than the current gold standard subtyping method, pulsed-field gel electrophoresis (PFGE). Furthermore, results could be obtained in a time frame suitable for surveillance activities, supporting the use of WGS as an outbreak detection and characterization method for S. Enteritidis. PMID- 26269624 TI - Performance of the CLSI Carba NP and the Rosco Carb Screen Assays Using North American Carbapenemase-Producing Enterobacteriaceae and Pseudomonas aeruginosa Isolates. AB - This study compared the performance of the Carba NP assay, published by the Clinical and Laboratory Standards Institute, and the Rosco Rapid Carb Screen kit. Carba NP had superior sensitivity, but both assays required an increased inoculum to detect carbapenemase production in isolates with blaNDM, blaIMP, and blaOXA 48. PMID- 26269625 TI - Association between Obesity and Cervical Microflora Dominated by Lactobacillus iners in Korean Women. AB - Lactobacillus spp. are associated with the maintenance of reproductive health, but obesity reduces fertility and is a risk factor for obstetric and neonatal complications. We assessed the association between obesity and the cervical Lactobacillus composition, which has not been examined previously. Pyrosequencing was performed using cervical swabs collected from 76 normal participants with negative results for cervical intraepithelial neoplasia (CIN) and 57 participants with CIN, based on histological examinations. Cluster analysis of nine Lactobacillus spp. was performed, and five cluster types were identified. The association between obesity and the Lactobacillus community was assessed by logistic regression analysis after adjustment for confounding factors. The proportion of Lactobacillus iners increased and that of Lactobacillus crispatus decreased according to body mass index (BMI) categories, i.e., underweight (BMI of <18.5 kg m(-2)), normal weight (BMI of 18.5 to 22.9 kg m(-2)), overweight (BMI of 23.0 to 24.9 kg m(-2)), and obese (BMI of >=25 kg m(-2)). The L. iners dominant type had a significant association with obesity (odds ratio [OR], 7.55 [95% confidence interval [CI], 1.18 to 48.2]), compared to the L. crispatus dominant type. The group with high values for the ratio obtained by dividing the relative abundance of L. iners by that of L. crispatus had a significant association with obesity (OR, 6.54 [95% CI, 1.22 to 35.1]), compared to the low ratio group. Associations between obesity and the L. iners/L. crispatus ratio were observed among young women (OR, 6.26 [95% CI, 1.15 to 33.9]) but not older women and in the normal group (OR, 6.97 [95% CI, 1.20 to 70.4]) but not the CIN group. Obesity was associated with cervical microflora dominated by L. iners in reproductive-age women without dysplasia. PMID- 26269626 TI - SQUINT promotes stem cell homeostasis and floral meristem termination in Arabidopsis through APETALA2 and CLAVATA signalling. AB - Plant meristems harbour stem cells, which allow for the continuous production of new organs. Here, an analysis of the role of SQUINT (SQN) in stem cell dynamics in Arabidopsis is reported. A close examination of sqn mutants reveals defects that are very similar to that of weak clavata (clv) mutants, both in the flower meristem (increased number of floral organs, occasional delay in stem cell termination) and in the shoot apical meristem (meristem and central zone enlargement, occasional fasciation). sqn has a very mild effect in a clv mutant background, suggesting that SQN and the CLV genes act in the same genetic pathway. Accordingly, a loss-of-function allele of SQN strongly rescues the meristem abortion phenotype of plants that overexpress CLV3. Altogether, these data suggest that SQN is necessary for proper CLV signalling. SQN was shown to be required for normal accumulation of various miRNAs, including miR172. One of the targets of miR172, APETALA2 (AP2), antagonizes CLV signalling. The ap2-2 mutation strongly suppresses the meristem phenotypes of sqn, indicating that the effect of SQN on stem cell dynamics is largely, but not fully, mediated by the miR172/AP2 tandem. This study refines understanding of the intricate genetic networks that control both stem cell homeostasis and floral stem cell termination, two processes that are critical for the proper development and fertility of the plant. PMID- 26269627 TI - Mapping Functional Topography in the Macaque Ventral Visual Pathway. PMID- 26269628 TI - Regional Specificity of GABAergic Regulation of Cross-Modal Plasticity in Mouse Visual Cortex after Unilateral Enucleation. AB - In adult mice, monocular enucleation (ME) results in an immediate deactivation of the contralateral medial monocular visual cortex. An early restricted reactivation by open eye potentiation is followed by a late overt cross-modal reactivation by whiskers (Van Brussel et al., 2011). In adolescence (P45), extensive recovery of cortical activity after ME fails as a result of suppression or functional immaturity of the cross-modal mechanisms (Nys et al., 2014). Here, we show that dark exposure before ME in adulthood also prevents the late cross modal reactivation component, thereby converting the outcome of long-term ME into a more P45-like response. Because dark exposure affects GABAergic synaptic transmission in binocular V1 and the plastic immunity observed at P45 is reminiscent of the refractory period for inhibitory plasticity reported by Huang et al. (2010), we molecularly examined whether GABAergic inhibition also regulates ME-induced cross-modal plasticity. Comparison of the adaptation of the medial monocular and binocular cortices to long-term ME or dark exposure or a combinatorial deprivation revealed striking differences. In the medial monocular cortex, cortical inhibition via the GABAA receptor alpha1 subunit restricts cross modal plasticity in P45 mice but is relaxed in adults to allow the whisker mediated reactivation. In line, in vivo pharmacological activation of alpha1 subunit-containing GABAA receptors in adult ME mice specifically reduces the cross-modal aspect of reactivation. Together with region-specific changes in glutamate acid decarboxylase (GAD) and vesicular GABA transporter expression, these findings put intracortical inhibition forward as an important regulator of the age-, experience-, and cortical region-dependent cross-modal response to unilateral visual deprivation. SIGNIFICANCE STATEMENT: In adult mice, vision loss through one eye instantly reduces neuronal activity in the visual cortex. Strengthening of remaining eye inputs in the binocular cortex is followed by cross-modal adaptations in the monocular cortex, in which whiskers become a dominant nonvisual input source to attain extensive cortical reactivation. We show that the cross-modal component does not occur in adolescence because of increased intracortical inhibition, a phenotype that was mimicked in adult enucleated mice when treated with indiplon, a GABAA receptor alpha1 agonist. The cross-modal versus unimodal responses of the adult monocular and binocular cortices also mirror regional specificity in inhibitory alterations after visual deprivation. Understanding cross-modal plasticity in response to sensory loss is essential to maximize patient susceptibility to sensory prosthetics. PMID- 26269629 TI - The Parkinson's Disease-Associated Mutation LRRK2-G2019S Impairs Synaptic Plasticity in Mouse Hippocampus. AB - Parkinson's disease (PD) is a major movement disorder characterized by the loss of dopamine neurons and formation of Lewy bodies. Clinical and pathological evidence indicates that multiple brain regions are affected in PD in a spatiotemporal manner and are associated with a variety of motor and nonmotor symptoms, including disturbances in mood, executive function, and memory. The common PD-associated gene for leucine-rich repeat kinase, leucine-rich repeat kinase 2 (LRRK2), is highly expressed in brain regions that are involved with nonmotor functions, including the neocortex and hippocampus, but whether mutant LRRK2 contributes to neuronal dysfunction in these regions is unknown. Here, we use bacterial artificial chromosome transgenic mouse models of LRRK2 to explore potential nonmotor mechanisms of PD. Through electrophysiological analysis of the Schaffer collateral-CA1 synapse in dorsal hippocampus, we find that overexpression of LRRK2-G2019S increases basal synaptic efficiency through a postsynaptic mechanism, and disrupts long-term depression. Furthermore, these effects of the G2019S mutation are age dependent and can be normalized by acute inhibition of LRRK2 kinase activity. In contrast, overexpression of wild-type LRRK2 has no effect under the same conditions, suggesting a specific phenotype for the G2019S mutation. These results identify a pathogenic function of LRRK2 in the hippocampus that may contribute to nonmotor symptoms of PD. SIGNIFICANCE STATEMENT: Parkinson's disease (PD) is among the most common neurological diseases and is best known for its adverse effects on brain regions that control motor function, resulting in tremor, rigidity, and gait abnormalities. Less well appreciated are the psychiatric symptoms experienced by many PD patients, including depression and memory loss, which do not respond well to currently available treatments for PD. Here, we describe functional effects of a common PD linked mutation of leucine-rich repeat kinase 2 in the mouse hippocampus, an area of the brain that is responsible for encoding and retaining memories. By providing a potential mechanism for some of the cognitive symptoms produced by this mutation, our findings may lead to novel approaches for the treatment of nonmotor symptoms of PD. PMID- 26269630 TI - High-Affinity Nicotinic Receptors Modulate Spontaneous Cortical Up States In Vitro. AB - Nicotinic acetylcholine receptors (nAChRs) play an important role in the modulation of many cognitive functions but their role in integrated network activity remains unclear. This is at least partly because of the complexity of the cholinergic circuitry and the difficulty in comparing results from in vivo studies obtained under diverse experimental conditions and types of anesthetics. Hence the role of nAChRs in the synchronization of cortical activity during slow wave sleep is still controversial, with some studies showing they are involved in ACh-dependent EEG desynchronization, and others suggesting that this effect is mediated exclusively by muscarinic receptors. Here we use an in vitro model of endogenous network activity, in the form of recurring self-maintained depolarized states (Up states), which allows us to examine the role of high-affinity nAChRs on network dynamics in a simpler form of the cortical microcircuit. We find that mice lacking nAChRs containing the beta2-subunit (beta2-nAChRs) have longer and more frequent Up states, and that this difference is eliminated when beta2-nAChRs in wild-type mice are blocked. We further show that endogenously released ACh can modulate Up/Down states through the activation of both beta2- and alpha7 containing nAChRs, but through distinct mechanisms: alpha7-nAChRs affect only the termination of spontaneous Up states, while beta2-nAChRs also regulate their generation. Finally we provide evidence that the effects of beta2-subunit containing, but not alpha7-subunit-containing nAChRs, are mediated through GABAB receptors. To our knowledge this is the first study documenting direct nicotinic modulation of Up/Down state activity. SIGNIFICANCE STATEMENT: Through our experiments we were able to uncover a clear and previously disputed effect of nicotinic signaling in synchronized activity of neuronal networks of the cortex. We show that both high-affinity receptors (containing the beta2-subunit, beta2 nAChRs) and low-affinity receptors (containing the alpha7-subunit, alpha7-nAChRs) can regulate cortical network function exhibited in the form of Up/Down states. We further show that the effects of beta2-nAChRs, but not alpha7-nAChRs, are mediated through the activation of GABAB receptors. These results suggest a possible synthesis of seemingly contradictory results in the literature and could be valuable for informing computational models of cortical function and for guiding the search for therapeutic interventions. PMID- 26269632 TI - Phosphoinositide Modulation of Heteromeric Kv1 Channels Adjusts Output of Spiral Ganglion Neurons from Hearing Mice. AB - Spiral ganglion neurons (SGNs) relay acoustic code from cochlear hair cells to the brainstem, and their stimulation enables electrical hearing via cochlear implants. Rapid adaptation, a mechanism that preserves temporal precision, and a prominent feature of auditory neurons, is regulated via dendrotoxin-sensitive low threshold voltage-activated (LVA) K(+) channels. Here, we investigated the molecular physiology of LVA currents in SGNs cultured from mice following the onset of hearing (postnatal days 12-21). Kv1.1- and Kv1.2-specific toxins blocked the LVA currents in a comparable manner, suggesting that both subunits contribute to functional heteromeric channels. Confocal immunofluorescence in fixed cochlear sections localized both Kv1.1 and Kv1.2 subunits to specific neuronal microdomains, including the somatic membrane, juxtaparanodes, and the first heminode, which forms the spike initiation site of the auditory nerve. The spatial distribution of Kv1 immunofluorescence appeared mutually exclusive to that of Kv3.1b subunits, which mediate high-threshold voltage-activated currents. As Kv1.2-containing channels are positively modulated by membrane phosphoinositides, we investigated the influence of phosphatidylinositol-4,5 bisphosphate (PIP2) availability on SGN electrophysiology. Reducing PIP2 production using wortmannin, or sequestration of PIP2 using a palmitoylated peptide (PIP2-PP), slowed adaptation rate in SGN populations. PIP2-PP specifically inhibited the LVA current in SGNs, an effect reduced by intracellular dialysis of a nonhydrolysable analog of PIP2. PIP2-PP also inhibited heterologously expressed Kv1.1/Kv1.2 channels, recapitulating its effect in SGNs. Collectively, the data identify Kv1.1/Kv1.2 heteromeric channels as key regulators of action potential initiation and propagation in the auditory nerve, and suggest that modulation of these channels by endogenous phosphoinositides provides local control of membrane excitability. SIGNIFICANCE STATEMENT: Rapid spike adaptation is an important feature of auditory neurons that preserves temporal precision. In spiral ganglion neurons, the primary afferents in the cochlea, adaptation is regulated by heteromeric ion channels composed of Kv1.1 and Kv1.2 subunits. These subunits colocalize to common functional microdomains, such as juxtaparanodes and the somatic membrane. Activity of the heteromeric channels is controlled by cellular availability of PIP2, a membrane phospholipid. This mechanism provides an intrinsic regulation of output from the auditory nerve, which could be targeted for therapeutic adjustment of hearing sensitivity. PMID- 26269631 TI - Temporally Dissociable Contributions of Human Medial Prefrontal Subregions to Reward-Guided Learning. AB - In decision making, dorsal and ventral medial prefrontal cortex show a sensitivity to key decision variables, such as reward prediction errors. It is unclear whether these signals reflect parallel processing of a common synchronous input to both regions, for example from mesocortical dopamine, or separate and consecutive stages in reward processing. These two perspectives make distinct predictions about the relative timing of feedback-related activity in each of these regions, a question we address here. To reconstruct the unique temporal contribution of dorsomedial (dmPFC) and ventromedial prefrontal cortex (vmPFC) to simultaneously measured EEG activity in human subjects, we developed a novel trialwise fMRI-informed EEG analysis that allows dissociating correlated and overlapping sources. We show that vmPFC uniquely contributes a sustained activation profile shortly after outcome presentation, whereas dmPFC contributes a later and more peaked activation pattern. This temporal dissociation is expressed mainly in the alpha band for a vmPFC signal, which contrasts with a theta based dmPFC signal. Thus, our data show reward-related vmPFC and dmPFC responses have distinct time courses and unique spectral profiles, findings that support distinct functional roles in a reward-processing network. SIGNIFICANCE STATEMENT: Multiple subregions of the medial prefrontal cortex are known to be involved in decision making and learning, and expose similar response patterns in fMRI. Here, we used a novel approach to analyzing simultaneous EEG-fMRI that allows to dissociate the individual time courses of brain regions. We find that vmPFC and dmPFC have distinguishable time courses and time-frequency patterns. PMID- 26269633 TI - The Good, the Bad, and the Irrelevant: Neural Mechanisms of Learning Real and Hypothetical Rewards and Effort. AB - Natural environments are complex, and a single choice can lead to multiple outcomes. Agents should learn which outcomes are due to their choices and therefore relevant for future decisions and which are stochastic in ways common to all choices and therefore irrelevant for future decisions between options. We designed an experiment in which human participants learned the varying reward and effort magnitudes of two options and repeatedly chose between them. The reward associated with a choice was randomly real or hypothetical (i.e., participants only sometimes received the reward magnitude associated with the chosen option). The real/hypothetical nature of the reward on any one trial was, however, irrelevant for learning the longer-term values of the choices, and participants ought to have only focused on the informational content of the outcome and disregarded whether it was a real or hypothetical reward. However, we found that participants showed an irrational choice bias, preferring choices that had previously led, by chance, to a real reward in the last trial. Amygdala and ventromedial prefrontal activity was related to the way in which participants' choices were biased by real reward receipt. By contrast, activity in dorsal anterior cingulate cortex, frontal operculum/anterior insula, and especially lateral anterior prefrontal cortex was related to the degree to which participants resisted this bias and chose effectively in a manner guided by aspects of outcomes that had real and more sustained relationships with particular choices, suppressing irrelevant reward information for more optimal learning and decision making. SIGNIFICANCE STATEMENT: In complex natural environments, a single choice can lead to multiple outcomes. Human agents should only learn from outcomes that are due to their choices, not from outcomes without such a relationship. We designed an experiment to measure learning about reward and effort magnitudes in an environment in which other features of the outcome were random and had no relationship with choice. We found that, although people could learn about reward magnitudes, they nevertheless were irrationally biased toward repeating certain choices as a function of the presence or absence of random reward features. Activity in different brain regions in the prefrontal cortex either reflected the bias or reflected resistance to the bias. PMID- 26269634 TI - Sex Differences in Molecular Signaling at Inhibitory Synapses in the Hippocampus. AB - The possibility that mechanisms of synaptic modulation differ between males and females has far-reaching implications for understanding brain disorders that vary between the sexes. We found recently that 17beta-estradiol (E2) acutely suppresses GABAergic inhibition in the hippocampus of female rats through a sex specific estrogen receptor alpha (ERalpha), mGluR, and endocannabinoid-dependent mechanism. Here, we define the intracellular signaling that links ERalpha, mGluRs, and endocannabinoids in females and identify where in this pathway males and females differ. Using a combination of whole-cell patch-clamp recording and biochemical analyses in hippocampal slices from young adult rats, we show that E2 acutely suppresses inhibition in females through mGluR1 stimulation of phospholipase C, leading to inositol triphosphate (IP3) generation, activation of the IP3 receptor (IP3R), and postsynaptic endocannabinoid release, likely of anandamide. Analysis of sex differences in this pathway showed that E2 stimulates a much greater increase in IP3 levels in females than males, whereas the group I mGluR agonist DHPG increases IP3 levels equivalently in each sex. Coimmunoprecipitation showed that ERalpha-mGluR1 and mGluR1-IP3R complexes exist in both sexes but are regulated by E2 only in females. Independently of E2, a fatty acid amide hydrolase inhibitor, which blocks breakdown of anandamide, suppressed >50% of inhibitory synapses in females with no effect in males, indicating tonic endocannabinoid release in females that is absent in males. Together, these studies demonstrate sex differences in both E2-dependent and E2 independent regulation of the endocannabinoid system and suggest that manipulation of endocannabinoids in vivo could affect physiological and behavioral responses differently in each sex. SIGNIFICANCE STATEMENT: Many brain disorders vary between the sexes, yet the degree to which this variation arises from differential experience versus intrinsic biological sex differences is unclear. In this study, we demonstrate intrinsic sex differences in molecular regulation of a key neuromodulatory system, the endocannabinoid system, in the hippocampus. Endocannabinoids are involved in diverse aspects of physiology and behavior that involve the hippocampus, including cognitive and motivational state, responses to stress, and neurological disorders such as epilepsy. Our finding that molecular regulation of the endocannabinoid system differs between the sexes suggests mechanisms through which experiences or therapeutics that engage endocannabinoids could affect males and females differently. PMID- 26269635 TI - Zic2 Controls the Migration of Specific Neuronal Populations in the Developing Forebrain. AB - Human mutations in ZIC2 have been identified in patients with holoprosencephaly and schizophrenia. Similarly, Zic2 mutant mice exhibit holoprosencephaly in homozygosis and behavioral and morphological schizophrenic phenotypes associated with forebrain defects in heterozygosis. Despite the devastating effects of mutations in Zic2, the cellular and molecular mechanisms that provoke Zic2 deficiency phenotypes are yet unclear. Here, we report a novel role for this transcription factor in the migration of three different types of forebrain neurons: the Cajal-Retzius cells that populate the surface of the telencephalic vesicles, an amygdaloid group of cells originated in the caudal pole of the telencephalic pallium, and a cell population that travels from the prethalamic neuroepithelium to the ventral lateral geniculate nucleus. Our results also suggest that the receptor EphB1, previously identified as a Zic2 target, may mediate, at least partially, Zic2-dependent migratory events. According to these results, we propose that deficiencies in cell motility and guidance contribute to most of the forebrain pathologies associated with Zic2 mutations. SIGNIFICANCE STATEMENT: Although the phenotype of Zic2 mutant individuals was reported more than 10 years ago, until now, the main function of this transcription factor during early development has not been precisely defined. Here, we reveal a previously unknown role for Zic2 in the migration of forebrain neurons such as Cajal-Retzius cells, interneurons moving to the ventral lateral geniculate nucleus, and neocortical cells going to the amygdala. We believe that the role of this transcription factor in certain populations of migratory cells contributes to defects in cortical layering and hypocellularity in the ventral LGN and amygdala and will contribute to our understanding of the devastating phenotypes associated with Zic2 mutations in both humans and mice. PMID- 26269636 TI - Neuronal Interleukin-4 as a Modulator of Microglial Pathways and Ischemic Brain Damage. AB - After ischemic stroke, various damage-associated molecules are released from the ischemic core and diffuse to the ischemic penumbra, activating microglia and promoting proinflammatory responses that may cause damage to the local tissue. Here we demonstrate using in vivo and in vitro models that, during sublethal ischemia, local neurons rapidly produce interleukin-4 (IL-4), a cytokine with potent anti-inflammatory properties. One such anti-inflammatory property includes its ability to polarize macrophages away from a proinflammatory M1 phenotype to a "healing" M2 phenotype. Using an IL-4 reporter mouse, we demonstrated that IL-4 expression was induced preferentially in neurons in the ischemic penumbra but not in the ischemic core or in brain regions that were spared from ischemia. When added to cultured microglia, IL-4 was able to induce expression of genes typifying the M2 phenotype and peroxisome proliferator activated receptor gamma (PPARgamma) activation. IL-4 also enhanced expression of the IL-4 receptor on microglia, facilitating a "feedforward" increase in (1) their expression of trophic factors and (2) PPARgamma-dependent phagocytosis of apoptotic neurons. Parenteral administration of IL-4 resulted in augmented brain expression of M2- and PPARgamma-related genes. Furthermore, IL-4 and PPARgamma agonist administration improved functional recovery in a clinically relevant mouse stroke model, even if administered 24 h after the onset of ischemia. We propose that IL 4 is secreted by ischemic neurons as an endogenous defense mechanism, playing a vital role in the regulation of brain cleanup and repair after stroke. Modulation of IL-4 and its associated pathways could represent a potential target for ischemic stroke treatment. SIGNIFICANCE STATEMENT: Depending on the activation signal, microglia/macrophages (MPhi) can behave as "healing" (M2) or "harmful" (M1). In response to ischemia, damaged/necrotic brain cells discharge factors that polarize MPhi to a M1-like phenotype. This polarization emerges early after stroke and persists for days to weeks, driving secondary brain injury via proinflammatory mediators and oxidative damage. Our study demonstrates that, to offset this M1-like polarization process, sublethally ischemic neurons may instead secrete a potent M2 polarizing cytokine, interleukin-4 (IL-4). In the presence of IL-4 (including when IL-4 is administered exogenously), MPhi become more effective in the cleanup of ischemic debris and produce trophic factors that may promote brain repair. We propose that IL-4 could represent a potential target for ischemic stroke treatment/recovery. PMID- 26269638 TI - Longitudinal Changes in Prefrontal Cortex Activation Underlie Declines in Adolescent Risk Taking. AB - Adolescence is a critical developmental phase during which risk-taking behaviors increase across a variety of species, raising the importance of understanding how brain changes contribute to such behaviors. While the prefrontal cortex is thought to influence adolescent risk taking, the specific ways in which it functions are unclear. Using longitudinal functional magnetic resonance imaging in human adolescents, we found that ventrolateral prefrontal cortex (VLPFC) activation decreased during an experimental risk-taking task over time, with greater declines in VLPFC associated with greater declines in self-reported risky behavior. Furthermore, greater decreases in functional coupling between the medial prefrontal cortex (MPFC) and ventral striatum over time were associated with decreases in self-reported risky behavior. Thus, disparate roles of the VLPFC and MPFC modulate longitudinal declines in adolescent risk taking. SIGNIFICANCE STATEMENT: Adolescence is a developmental period marked by steep increases in risk-taking behavior coupled with dramatic brain changes. Although theories propose that the prefrontal cortex (PFC) may influence adolescent risk taking, the specific ways in which it functions remain unclear. We report the first longitudinal functional magnetic resonance imaging study to examine how neural activation during risk taking changes over time and contributes to adolescents' real-life risk-taking behavior. We find that longitudinal declines in activation of the ventrolateral PFC are linked to declines in adolescent risk taking, whereas the medial PFC influences adolescent risk taking via its functional neural coupling with reward-related regions. This is the first study to identify the mechanism by which different regions of the PFC disparately contribute to declines in risk taking. PMID- 26269637 TI - Neuronal Atrophy Early in Degenerative Ataxia Is a Compensatory Mechanism to Regulate Membrane Excitability. AB - Neuronal atrophy in neurodegenerative diseases is commonly viewed as an early event in a continuum that ultimately results in neuronal loss. In a mouse model of the polyglutamine disorder spinocerebellar ataxia type 1 (SCA1), we tested the hypothesis that cerebellar Purkinje neuron atrophy serves an adaptive role rather than being simply a nonspecific response to injury. In acute cerebellar slices from SCA1 mice, we find that Purkinje neuron pacemaker firing is initially normal but, with the onset of motor dysfunction, becomes disrupted, accompanied by abnormal depolarization. Remarkably, subsequent Purkinje cell atrophy is associated with a restoration of pacemaker firing. The early inability of Purkinje neurons to support repetitive spiking is due to unopposed calcium currents resulting from a reduction in large-conductance calcium-activated potassium (BK) and subthreshold-activated potassium channels. The subsequent restoration of SCA1 Purkinje neuron firing correlates with the recovery of the density of these potassium channels that accompanies cell atrophy. Supporting a critical role for BK channels, viral-mediated increases in BK channel expression in SCA1 Purkinje neurons improves motor dysfunction and partially restores Purkinje neuron morphology. Cerebellar perfusion of flufenamic acid, an agent that restores the depolarized membrane potential of SCA1 Purkinje neurons by activating potassium channels, prevents Purkinje neuron dendritic atrophy. These results suggest that Purkinje neuron dendritic remodeling in ataxia is an adaptive response to increases in intrinsic membrane excitability. Similar adaptive remodeling could apply to other vulnerable neuronal populations in neurodegenerative disease. SIGNIFICANCE STATEMENT: In neurodegenerative disease, neuronal atrophy has long been assumed to be an early nonspecific event preceding neuronal loss. However, in a mouse model of spinocerebellar ataxia type 1 (SCA1), we identify a previously unappreciated compensatory role for neuronal shrinkage. Purkinje neuron firing in these mice is initially normal, but is followed by abnormal membrane depolarization resulting from a reduction in potassium channels. Subsequently, these electrophysiological effects are counteracted by cell atrophy, which by restoring normal potassium channel membrane density, re establishes pacemaker firing. Reversing the initial membrane depolarization improved motor function and Purkinje neuron morphology in the SCA1 mice. These results suggest that Purkinje neuron remodeling in ataxia is an active compensatory response that serves to normalize intrinsic membrane excitability. PMID- 26269639 TI - Exchange Protein Directly Activated by cAMP (EPAC) Regulates Neuronal Polarization through Rap1B. AB - Acquisition of neuronal polarity is a complex process involving cellular and molecular events. The second messenger cAMP is involved in axonal specification through activation of protein kinase A. However, an alternative cAMP-dependent mechanism involves the exchange protein directly activated by cAMP (EPAC), which also responds to physiological changes in cAMP concentration, promoting activation of the small Rap GTPases. Here, we present evidence that EPAC signaling contributes to axon specification and elongation. In primary rat hippocampal neurons, EPAC isoforms were expressed differentially during axon specification. Furthermore, 8-pCPT, an EPAC pharmacological activator, and genetic manipulations of EPAC in neurons induced supernumerary axons indicative of Rap1b activation. Moreover, 8-pCPT-treated neurons expressed ankyrin G and other markers of mature axons such as synaptophysin and axonal accumulation of vGLUT1. In contrast, pharmacological inhibition of EPAC delayed neuronal polarity. Genetic manipulations to inactivate EPAC1 using either shRNA or neurons derived from EPAC1 knock-out (KO) mice led to axon elongation and polarization defects. Interestingly, multiaxonic neurons generated by 8-pCPT treatments in wild-type neurons were not found in EPAC1 KO mice neurons. Altogether, these results propose that EPAC signaling is an alternative and complementary mechanism for cAMP-dependent axon determination. SIGNIFICANCE STATEMENT: This study identifies the guanine exchange factor responsible for Rap1b activation during neuronal polarization and provides an alternate explanation for cAMP-dependent acquisition of neuronal polarity. PMID- 26269640 TI - Adult Hippocampal Neurogenesis Modulates Fear Learning through Associative and Nonassociative Mechanisms. AB - Adult hippocampal neurogenesis is believed to support hippocampus-dependent learning and emotional regulation. These putative functions of adult neurogenesis have typically been studied in isolation, and little is known about how they interact to produce adaptive behavior. We used trace fear conditioning as a model system to elucidate mechanisms through which adult hippocampal neurogenesis modulates processing of aversive experience. To achieve a specific ablation of neurogenesis, we generated transgenic mice that express herpes simplex virus thymidine kinase specifically in neural progenitors and immature neurons. Intracerebroventricular injection of the prodrug ganciclovir caused a robust suppression of neurogenesis without suppressing gliogenesis. Neurogenesis ablation via this method or targeted x-irradiation caused an increase in context conditioning in trace but not delay fear conditioning. Data suggest that this phenotype represents opposing effects of neurogenesis ablation on associative and nonassociative components of fear learning. Arrest of neurogenesis sensitizes mice to nonassociative effects of fear conditioning, as evidenced by increased anxiety-like behavior in the open field after (but not in the absence of) fear conditioning. In addition, arrest of neurogenesis impairs associative trace conditioning, but this impairment can be masked by nonassociative fear. The results suggest that adult neurogenesis modulates emotional learning via two distinct but opposing mechanisms: it supports associative trace conditioning while also buffering against the generalized fear and anxiety caused by fear conditioning. SIGNIFICANCE STATEMENT: The role of adult hippocampal neurogenesis in fear learning is controversial, with some studies suggesting neurogenesis is needed for aspects of fear learning and others suggesting it is dispensable. We generated transgenic mice in which neural progenitors can be selectively and inducibly ablated. Our data suggest that adult neurogenesis supports fear learning through two distinct mechanisms: it supports the ability to learn associations between traumatic events (unconditioned stimuli) and predictors (conditioned stimuli) while also buffering against nonassociative, anxiogenic effects of a traumatic experience. As a result, arrest of neurogenesis can enhance or impair learned fear depending on intensity of the traumatic experience and the extent to which it recruits associative versus nonassociative learning. PMID- 26269641 TI - Defective Age-Dependent Metaplasticity in a Mouse Model of Alzheimer's Disease. AB - Much of the molecular understanding of synaptic pathology in Alzheimer's disease (AD) comes from studies of various mouse models that express familial AD (FAD) linked mutations, often in combinations. Most studies compare the absolute magnitudes of long-term potentiation (LTP) and long-term depression (LTD) to assess deficits in bidirectional synaptic plasticity accompanying FAD-linked mutations. However, LTP and LTD are not static, but their induction threshold is adjusted by overall neural activity via metaplasticity. Hence LTP/LTD changes in AD mouse models may reflect defects in metaplasticity processes. To determine this, we examined the LTP/LTD induction threshold in APPswe;PS1DeltaE9 transgenic (Tg) mice across two different ages. We found that in young Tg mice (1 month), LTP is enhanced at the expense of LTD, but in adults (6 months), the phenotype is reversed to promote LTD and reduce LTP, compared to age-matched wild-type (WT) littermates. The apparent opposite phenotype across age was due to an initial offset in the induction threshold to favor LTP and the inability to undergo developmental metaplasticity in Tg mice. In WTs, the synaptic modification threshold decreased over development to favor LTP and diminish LTD in adults. However, in Tg mice, the magnitudes of LTP and LTD stayed constant across development. The initial offset in LTP/LTD threshold in young Tg mice did not accompany changes in the LTP/LTD induction mechanisms, but altered AMPA receptor phosphorylation and appearance of Ca(2+)-permeable AMPA receptors. We propose that the main synaptic defect in AD mouse models is due to their inability to undergo developmental metaplasticity. SIGNIFICANCE STATEMENT: This work offers a new insight that metaplasticity defects are central to synaptic dysfunctions seen in AD mouse models. In particular, we demonstrate that the apparent differences in LTP/LTD magnitude seen across ages in AD transgenic mouse models reflect the inability to undergo a normal developmental shift in metaplasticity. PMID- 26269642 TI - Influences of Long-Term Memory-Guided Attention and Stimulus-Guided Attention on Visuospatial Representations within Human Intraparietal Sulcus. AB - Human parietal cortex plays a central role in encoding visuospatial information and multiple visual maps exist within the intraparietal sulcus (IPS), with each hemisphere symmetrically representing contralateral visual space. Two forms of hemispheric asymmetries have been identified in parietal cortex ventrolateral to visuotopic IPS. Key attentional processes are localized to right lateral parietal cortex in the temporoparietal junction and long-term memory (LTM) retrieval processes are localized to the left lateral parietal cortex in the angular gyrus. Here, using fMRI, we investigate how spatial representations of visuotopic IPS are influenced by stimulus-guided visuospatial attention and by LTM-guided visuospatial attention. We replicate prior findings that a hemispheric asymmetry emerges under stimulus-guided attention: in the right hemisphere (RH), visual maps IPS0, IPS1, and IPS2 code attentional targets across the visual field; in the left hemisphere (LH), IPS0-2 codes primarily contralateral targets. We report the novel finding that, under LTM-guided attention, both RH and LH IPS0-2 exhibit bilateral responses and hemispheric symmetry re-emerges. Therefore, we demonstrate that both hemispheres of IPS0-2 are independently capable of dynamically changing spatial coding properties as attentional task demands change. These findings have important implications for understanding visuospatial and memory-retrieval deficits in patients with parietal lobe damage. SIGNIFICANCE STATEMENT: The human parietal lobe contains multiple maps of the external world that spatially guide perception, action, and cognition. Maps in each cerebral hemisphere code information from the opposite side of space, not from the same side, and the two hemispheres are symmetric. Paradoxically, damage to specific parietal regions that lack spatial maps can cause patients to ignore half of space (hemispatial neglect syndrome), but only for right (not left) hemisphere damage. Conversely, the left parietal cortex has been linked to retrieval of vivid memories regardless of space. Here, we investigate possible underlying mechanisms in healthy individuals. We demonstrate two forms of dynamic changes in parietal spatial representations: an asymmetric one for stimulus-guided attention and a symmetric one for long-term memory-guided attention. PMID- 26269643 TI - Ca2+ Diffusion through Endoplasmic Reticulum Supports Elevated Intraterminal Ca2+ Levels Needed to Sustain Synaptic Release from Rods in Darkness. AB - In addition to vesicle release at synaptic ribbons, rod photoreceptors are capable of substantial slow release at non-ribbon release sites triggered by Ca(2+)-induced Ca(2+) release (CICR) from intracellular stores. To maintain CICR as rods remain depolarized in darkness, we hypothesized that Ca(2+) released into the cytoplasm from terminal endoplasmic reticulum (ER) can be replenished continuously by ions diffusing within the ER from the soma. We measured [Ca(2+)] changes in cytoplasm and ER of rods from Ambystoma tigrinum retina using various dyes. ER [Ca(2+)] changes were measured by loading ER with fluo-5N and then washing dye from the cytoplasm with a dye-free patch pipette solution. Small dye molecules diffused within ER between soma and terminal showing a single continuous ER compartment. Depolarization of rods to -40 mV depleted Ca(2+) from terminal ER, followed by a decline in somatic ER [Ca(2+)]. Local activation of ryanodine receptors in terminals with a spatially confined puff of ryanodine caused a decline in terminal ER [Ca(2+)], followed by a secondary decrease in somatic ER. Localized photolytic uncaging of Ca(2+) from o-nitrophenyl-EGTA in somatic ER caused an abrupt Ca(2+) increase in somatic ER, followed by a slower Ca(2+) increase in terminal ER. These data suggest that, during maintained depolarization, a soma-to-terminal [Ca(2+)] gradient develops within the ER that promotes diffusion of Ca(2+) ions to resupply intraterminal ER Ca(2+) stores and thus sustain CICR-mediated synaptic release. The ability of Ca(2+) to move freely through the ER may also promote bidirectional communication of Ca(2+) changes between soma and terminal. SIGNIFICANCE STATEMENT: Vertebrate rod and cone photoreceptors both release vesicles at synaptic ribbons, but rods also exhibit substantial slow release at non-ribbon sites triggered by Ca(2+)-induced Ca(2+) release (CICR). Blocking CICR inhibits >50% of release from rods in darkness. How do rods maintain sufficiently high [Ca(2+)] in terminal endoplasmic reticulum (ER) to support sustained CICR-driven synaptic transmission? We show that maintained depolarization creates a [Ca(2+)] gradient within the rod ER lumen that promotes soma-to-terminal diffusion of Ca(2+) to replenish intraterminal ER stores. This mechanism allows CICR-triggered synaptic release to be sustained indefinitely while rods remain depolarized in darkness. Free diffusion of Ca(2+) within the ER may also communicate synaptic Ca(2+) changes back to the soma to influence other critical cell processes. PMID- 26269644 TI - Bidirectional Regulation of Amyloid Precursor Protein-Induced Memory Defects by Nebula/DSCR1: A Protein Upregulated in Alzheimer's Disease and Down Syndrome. AB - Aging individuals with Down syndrome (DS) have an increased risk of developing Alzheimer's disease (AD), a neurodegenerative disorder characterized by impaired memory. Memory problems in both DS and AD individuals usually develop slowly and progressively get worse with age, but the cause of this age-dependent memory impairment is not well understood. This study examines the functional interactions between Down syndrome critical region 1 (DSCR1) and amyloid precursor protein (APP), proteins upregulated in both DS and AD, in regulating memory. Using Drosophila as a model, we find that overexpression of nebula (fly homolog of DSCR1) initially protects against APP-induced memory defects by correcting calcineurin and cAMP signaling pathways but accelerates the rate of memory loss and exacerbates mitochondrial dysfunction in older animals. We report that transient upregulation of Nebula/DSCR1 or acute pharmacological inhibition of calcineurin in aged flies protected against APP-induced memory loss. Our data suggest that calcineurin dyshomeostasis underlies age-dependent memory impairments and further imply that chronic Nebula/DSCR1 upregulation may contribute to age-dependent memory impairments in AD in DS. SIGNIFICANCE STATEMENT: Most Down syndrome (DS) individuals eventually develop Alzheimer's disease (AD)-like dementia, but mechanisms underlying this age-dependent memory impairment remain poorly understood. This study examines Nebula/Down syndrome critical region 1 (DSCR1) and amyloid-precursor protein (APP), proteins upregulated in both DS and AD, in regulating memory. We uncover a previously unidentified role for Nebula/DSCR1 in modulating APP-induced memory defects during aging. We show that upregulation of Nebula/DSCR1, an inhibitor of calcineurin, rescues APP-induced memory defects in young flies but enhances memory loss of older flies. Excitingly, transient Nebula/DSCR1 overexpression or calcineurin inhibition in aged flies ameliorates APP-mediated memory problems. These results suggest that chronic Nebula/DSCR1 upregulation may contribute to age-dependent memory loss in DS and AD and points to correcting calcineurin signaling as a means to improve memory during aging. PMID- 26269645 TI - Oligodendrocytes Are Targets of HIV-1 Tat: NMDA and AMPA Receptor-Mediated Effects on Survival and Development. AB - Myelin pallor in HIV(+) individuals can occur very early during the disease process. While myelin damage might partly originate from HIV-induced vascular changes, the timing suggests that myelin and/or oligodendrocytes (OLs) may be directly affected. Histological (Golgi-Kopsch, electron microscopy) and biochemical studies have revealed an increased occurrence of abnormal OL/myelin morphology and dysregulated myelin protein expression in transgenic mice expressing the HIV-1 transactivator of transcription (Tat) protein. This suggests that viral proteins by themselves might cause OL injury. Since Tat interacts with NMDARs, we hypothesized that activation of NMDARs and subsequent disruption of cytoplasmic Ca(2+) ([Ca(2+)]i) homeostasis might be one cause of white matter injury after HIV infection. In culture, HIV-1 Tat caused concentration-dependent death of immature OLs, while more mature OLs remained alive but had reduced myelin-like membranes. Tat also induced [Ca(2+)]i increases and Thr-287 autophosphorylation of Ca(2+)/calmodulin-dependent protein kinase II beta (CaMKIIbeta) in OLs. Tat-induced [Ca(2+)]i was attenuated by the NMDAR antagonist MK801, and also by the AMPA/kainate receptor antagonist CNQX. Importantly, both MK801 and CNQX blocked Tat-induced death of immature OLs, but only MK801 reversed Tat effects on myelin-like membranes. These results suggest that OLs can be direct targets of HIV proteins released from infected cells. Although viability and membrane production are both affected by glutamatergic receptor-mediated Ca(2+) influx, and possibly the ensuing CaMKIIbeta activation, the roles of AMPARs and NMDARs appear to be different and dependent on the stage of OL differentiation. SIGNIFICANCE STATEMENT: Over 33 million individuals are currently infected by HIV. Among these individuals, ~60% develop HIV-associated neurocognitive disorders. Myelin damage and white matter injury have been frequently reported in HIV patients but not extensively studied. Clinical studies using combined antiretroviral therapy (cART) together with adjunctive "anti inflammatory" drugs show no improvement over cART alone, suggesting existence of injury mechanisms in addition to inflammation. In our studies, oligodendrocytes exhibited rapid increases in intracellular Ca(2+) level upon HIV-1 transactivator of transcription (Tat) exposure. Thus, immature and mature oligodendrocytes can be direct targets of Tat. Since ionotropic glutamate receptor antagonists can partially or fully reverse the detrimental effects of Tat, glutamate receptors could be a potential therapeutic target for white matter damage in HIV patients. PMID- 26269647 TI - Predicting Reaction Time from the Neural State Space of the Premotor and Parietal Grasping Network. AB - Neural networks of the brain involved in the planning and execution of grasping movements are not fully understood. The network formed by macaque anterior intraparietal area (AIP) and hand area (F5) of the ventral premotor cortex is implicated strongly in the generation of grasping movements. However, the differential role of each area in this frontoparietal network is unclear. We recorded spiking activity from many electrodes in parallel in AIP and F5 while three macaque monkeys (Macaca mulatta) performed a delayed grasping task. By analyzing neural population activity during action preparation, we found that state space analysis of simultaneously recorded units is significantly more predictive of subsequent reaction times (RTs) than traditional methods. Furthermore, because we observed a wide variety of individual unit characteristics, we developed the sign-corrected average rate (SCAR) method of neural population averaging. The SCAR method was able to explain at least as much variance in RT overall as state space methods. Overall, F5 activity predicted RT (18% variance explained) significantly better than AIP (6%). The SCAR methods provides a straightforward interpretation of population activity, although other state space methods could provide richer descriptions of population dynamics. Together, these results lend support to the differential role of the parietal and frontal cortices in preparation for grasping, suggesting that variability in preparatory activity in F5 has a more potent effect on trial-to-trial RT variability than AIP. SIGNIFICANCE STATEMENT: Grasping movements are planned before they are executed, but how is the preparatory activity in a population of neurons related to the subsequent reaction time (RT)? A population analysis of the activity of many neurons recorded in parallel in macaque premotor (F5) and parietal (AIP) cortices during a delayed grasping task revealed that preparatory activity in F5 could explain a threefold larger fraction of variability in trial to-trial RT than AIP. These striking differences lend additional support to a differential role of the parietal and premotor cortices in grasp movement preparation, suggesting that F5 has a more direct influence on trial-to-trial variability and movement timing, whereas AIP might be more closely linked to overall movement intentions. PMID- 26269646 TI - The Autotaxin-Lysophosphatidic Acid Axis Modulates Histone Acetylation and Gene Expression during Oligodendrocyte Differentiation. AB - During development, oligodendrocytes (OLGs), the myelinating cells of the CNS, undergo a stepwise progression during which OLG progenitors, specified from neural stem/progenitor cells, differentiate into fully mature myelinating OLGs. This progression along the OLG lineage is characterized by well synchronized changes in morphology and gene expression patterns. The latter have been found to be particularly critical during the early stages of the lineage, and they have been well described to be regulated by epigenetic mechanisms, especially by the activity of the histone deacetylases HDAC1 and HDAC2. The data presented here identify the extracellular factor autotaxin (ATX) as a novel upstream signal modulating HDAC1/2 activity and gene expression in cells of the OLG lineage. Using the zebrafish as an in vivo model system as well as rodent primary OLG cultures, this functional property of ATX was found to be mediated by its lysophospholipase D (lysoPLD) activity, which has been well characterized to generate the lipid signaling molecule lysophosphatidic acid (LPA). More specifically, the lysoPLD activity of ATX was found to modulate HDAC1/2 regulated gene expression during a time window coinciding with the transition from OLG progenitor to early differentiating OLG. In contrast, HDAC1/2 regulated gene expression during the transition from neural stem/progenitor to OLG progenitor appeared unaffected by ATX and its lysoPLD activity. Thus, together, our data suggest that an ATX-LPA-HDAC1/2 axis regulates OLG differentiation specifically during the transition from OLG progenitor to early differentiating OLG and via a molecular mechanism that is evolutionarily conserved from at least zebrafish to rodent. SIGNIFICANCE STATEMENT: The formation of the axon insulating and supporting myelin sheath by differentiating oligodendrocytes (OLGs) in the CNS is considered an essential step during vertebrate development. In addition, loss and/or dysfunction of the myelin sheath has been associated with a variety of neurologic diseases in which repair is limited, despite the presence of progenitor cells with the potential to differentiate into myelinating OLGs. This study characterizes the autotaxin-lysophosphatidic acid signaling axis as a modulator of OLG differentiation in vivo in the developing zebrafish and in vitro in rodent OLGs in culture. These findings provide novel insight into the regulation of developmental myelination, and they are likely to lead to advancing studies related to the stimulation of myelin repair under pathologic conditions. PMID- 26269649 TI - Concurrent TMS-fMRI Reveals Interactions between Dorsal and Ventral Attentional Systems. AB - Adaptive behavior relies on combining bottom-up sensory inputs with top-down control signals to guide responses in line with current goals and task demands. Over the past decade, accumulating evidence has suggested that the dorsal and ventral frontoparietal attentional systems are recruited interactively in this process. This fMRI study used concurrent transcranial magnetic stimulation (TMS) as a causal perturbation approach to investigate the interactions between dorsal and ventral attentional systems and sensory processing areas. In a sustained spatial attention paradigm, human participants detected weak visual targets that were presented in the lower-left visual field on 50% of the trials. Further, we manipulated the presence/absence of task-irrelevant auditory signals. Critically, on each trial we applied 10 Hz bursts of four TMS (or Sham) pulses to the intraparietal sulcus (IPS). IPS-TMS relative to Sham-TMS increased activation in the parietal cortex regardless of sensory stimulation, confirming the neural effectiveness of TMS stimulation. Visual targets increased activations in the anterior insula, a component of the ventral attentional system responsible for salience detection. Conversely, they decreased activations in the ventral visual areas. Importantly, IPS-TMS abolished target-evoked activation increases in the right temporoparietal junction (TPJ) of the ventral attentional system, whereas it eliminated target-evoked activation decreases in the right fusiform. Our results demonstrate that IPS-TMS exerts profound directional causal influences not only on visual areas but also on the TPJ as a critical component of the ventral attentional system. They reveal a complex interplay between dorsal and ventral attentional systems during target detection under sustained spatial attention. SIGNIFICANCE STATEMENT: Adaptive behavior relies on combining bottom up sensory inputs with top-down attentional control. Although the dorsal and ventral frontoparietal systems are key players in attentional control, their distinct contributions remain unclear. In this TMS-fMRI study, participants attended to the left visual field to detect weak visual targets presented on half of the trials. We applied brief TMS bursts (or Sham-TMS) to the dorsal intraparietal sulcus (IPS) 100 ms after visual stimulus onset. IPS-TMS abolished the visual induced response suppression in the ventral occipitotemporal cortex and the response enhancement to visual targets in the temporoparietal junction. Our results demonstrate that IPS causally influences neural activity in the ventral attentional system 100 ms poststimulus. They have important implications for our understanding of the neural mechanisms underlying attentional control. PMID- 26269648 TI - Selective Loss of Presynaptic Potassium Channel Clusters at the Cerebellar Basket Cell Terminal Pinceau in Adam11 Mutants Reveals Their Role in Ephaptic Control of Purkinje Cell Firing. AB - A specialized axonal ending, the basket cell "pinceau," encapsulates the Purkinje cell axon initial segment (AIS), exerting final inhibitory control over the integrated outflow of the cerebellar cortex. This nonconventional axo-axonic contact extends beyond the perisomatic chemical GABAergic synaptic boutons to the distal AIS, lacks both sodium channels and local exocytotic machinery, and yet contains a dense cluster of voltage-gated potassium channels whose functional contribution is unknown. Here, we show that ADAM11, a transmembrane noncatalytic disintegrin, is the first reported Kv1-interacting protein essential for localizing Kv1.1 and Kv1.2 subunit complexes to the distal terminal. Selective absence of these channels at the pinceau due to mutation of ADAM11 spares spontaneous GABA release from basket cells at the perisomatic synapse yet eliminates ultrarapid ephaptic inhibitory synchronization of Purkinje cell firing. Our findings identify a critical role for presynaptic K(+) channels at the pinceau in ephaptic control over the speed and stability of spike rate coding at the Purkinje cell AIS in mice. SIGNIFICANCE STATEMENT: This study identifies ADAM11 as the first essential molecule for the proper localization of potassium ion channels at presynaptic nerve terminals, where they modulate excitability and the release of neural transmitters. Genetic truncation of the transmembrane disintegrin and metalloproteinase protein ADAM11 resulted in the absence of Kv1 channels that are normally densely clustered at the terminals of basket cell axons in the cerebellar cortex. These specialized terminals are responsible for the release of the neurotransmitter GABA onto Purkinje cells and also display electrical signaling. In the ADAM11 mutant, GABAergic release was not altered, but the ultrarapid electrical signal was absent, demonstrating that the dense presynaptic cluster of Kv1 ion channels at these terminals mediate electrical transmission. Therefore, ADAM11 plays a critical role at this central synapse. PMID- 26269650 TI - Mood symptoms correlate with kynurenine pathway metabolites following sports related concussion. AB - OBJECTIVE: An imbalance of neuroactive kynurenine pathway metabolites has been proposed as one mechanism behind the neuropsychiatric sequelae of certain neurological disorders. We hypothesized that concussed football players would have elevated plasma levels of neurotoxic kynurenine metabolites and reduced levels of neuroprotective metabolites relative to healthy football players and that altered kynurenine levels would correlate with post-concussion mood symptoms. METHODS: Mood scales and plasma concentrations of kynurenine metabolites were assessed in concussed (N=18; 1.61 days post-injury) and healthy football players (N=18). A subset of football players returned at 1-week (N=14; 9.29 days) and 1-month post-concussion (N=14, 30.93 days). RESULTS: Concussed athletes had significantly elevated levels of quinolinic acid (QUIN) and significantly lower ratios of kynurenic acid (KYNA) to QUIN at all time points compared with healthy athletes (p's<0.05), with no longitudinal evidence of normalization of KYNA or KYNA/QUIN. At 1-day post-injury, concussed athletes with lower levels of the putatively neuroprotective KYNA/QUIN ratio reported significantly worse depressive symptoms (p=0.04), and a trend toward worse anxiety symptoms (p=0.06), while at 1-month higher QUIN levels were associated with worse mood symptoms (p's<0.01). Finally, concussed athletes with worse concussion outcome, defined as number of days until return-to-play, had higher QUIN and lower KYNA/QUIN at 1-month post-injury (p's<0.05). CONCLUSIONS: These results converge with existing kynurenine literature on psychiatric patients and provide the first evidence of altered peripheral levels of kynurenine metabolites following sports-related concussion. PMID- 26269652 TI - Neuron-Specific Tumor Necrosis Factor Receptor-Associated Factor 3 and Acute Ischemic Stroke. PMID- 26269653 TI - Thresholds for Diagnosing Hypertension Based on Automated Office Blood Pressure Measurements and Cardiovascular Risk. AB - The risk of cardiovascular events in relation to blood pressure is largely based on readings taken with a mercury sphygmomanometer in populations which differ from those of today in terms of hypertension severity and drug therapy. Given replacement of the mercury sphygmomanometer with electronic devices, we sought to determine the blood pressure threshold for a significant increase in cardiovascular risk using a fully automated device, which takes multiple readings with the subject resting quietly alone. Participants were 3627 community-dwelling residents aged >65 years untreated for hypertension. Automated office blood pressure readings were obtained in a community pharmacy with subjects seated and undisturbed. This method for recording blood pressure produces similar readings in different settings, including a pharmacy and family doctor's office providing the above procedures are followed. Subjects were followed for a mean (SD) of 4.9 (1.0) years for fatal and nonfatal cardiovascular events. Adjusted hazard ratios (95% confidence intervals) were computed for 10 mm Hg increments in blood pressure (mm Hg) using Cox proportional hazards regression and the blood pressure category with the lowest event rate as the reference category. A total of 271 subjects experienced a cardiovascular event. There was a significant (P=0.02) increase in the hazard ratio of 1.66 (1.09, 2.54) at a systolic blood pressure of 135 to 144 and 1.72 (1.21, 2.45; P=0.003) at a diastolic blood pressure of 80 to 89. A significant (P=0.03) increase in hazard ratio of 1.73 (1.04, 2.86) occurred with a pulse pressure of 80 to 89. These findings are consistent with a threshold of 135/85 for diagnosing hypertension in older subjects using automated office blood pressure. PMID- 26269655 TI - Hypertension Editors' Picks: Environmental Factors, Pollution, and Hypertension. PMID- 26269654 TI - Neuron-Specific Tumor Necrosis Factor Receptor-Associated Factor 3 Is a Central Regulator of Neuronal Death in Acute Ischemic Stroke. AB - Neuronal death after ischemic stroke involves multiple pathophysiological events, as well as a complex molecular mechanism. Inhibiting a single therapeutic target that is involved in several ischemic signaling cascades may be a promising strategy for stroke management. Here, we report the versatile biological roles of tumor necrosis factor receptor-associated factor 3 (TRAF3) in ischemic stroke. Using several genetically manipulated mouse strains, we also demonstrated that TRAF3 inhibition can be neuroprotective. TRAF3 expression, which is robustly induced in response to ischemia/reperfusion (I/R) injury, was detected in neurons. Overexpression of TRAF3 in neurons led to aggravated neuronal loss and enlarged infarcts; these effects were reversed in TRAF3-knockout mice. Neuronal TRAF3 also contributed to c-Jun kinase-, nuclear factor kappaB- and Rac-1-induced neuronal death, inflammation, and oxidative stress. Mechanistically, we showed that TRAF3 interacts with transforming growth factor-beta-activated kinase 1 (TAK1) and potentiates phosphorylation and activation of TAK1. Phosphorylated TAK1 sequentially initiated activation of nuclear factor kappaB, Rac-1/NADPH oxidase, and c-Jun kinase/c-Jun signaling cascades. Using a combination of adenoviruses encoding dominant-negative TAK1 and the TAK1 inhibitor 5Z-7 oxozeaenol, we demonstrated that the TRAF3-mediated activation of ischemic cascades was TAK1-dependent. More importantly, the adverse phenotypes observed in TRAF3-overexpressing mice were completely reversed when the TRAF3-TAK1 interaction was prevented. Therefore, we have shown that TRAF3 is a central regulator of ischemic pathways, including nuclear factor kappaB, Rac-1, and c-Jun kinase signaling, via its interaction with and activation of TAK1. Furthermore, certain components of the TRAF3-TAK1 signaling pathway are potentially promising therapeutic targets in ischemic stroke. PMID- 26269656 TI - Mineralocorticoid excess or glucocorticoid insufficiency: renal and metabolic phenotypes in a rat Hsd11b2 knockout model. PMID- 26269657 TI - Wave separation, wave intensity, the reservoir-wave concept, and the instantaneous wave-free ratio: presumptions and principles. PMID- 26269658 TI - Diversity ? Inclusion: Promoting Integration in Higher Education. PMID- 26269659 TI - Learning Science-Based Fitness Knowledge in Constructivist Physical Education. AB - Teaching fitness-related knowledge has become critical in developing children's healthful living behavior. The purpose of this study was to examine the effects of a science-based, constructivist physical education curriculum on learning fitness knowledge critical to healthful living in elementary school students. The schools (N = 30) were randomly selected from one of the largest school districts in the United States and randomly assigned to treatment curriculum and control conditions. Students in third, fourth, and fifth grade (N = 5,717) were pre- and posttested on a standardized knowledge test on exercise principles and benefits in cardiorespiratory health, muscular capacity, and healthful nutrition and body flexibility. The results indicated that children in the treatment curriculum condition learned at a faster rate than their counterparts in the control condition. The results suggest that the constructivist curriculum is capable of inducing superior knowledge gain in third-, fourth-, and fifth-grade children. PMID- 26269660 TI - Investigating the Fundamentals of Molecular Depth Profiling Using Strong-field Photoionization of Sputtered Neutrals. AB - Molecular depth profiles of model organic thin films were performed using a 40 keV C60+ cluster ion source in concert with TOF-SIMS. Strong-field photoionization of intact neutral molecules sputtered by 40 keV C60+ primary ions was used to analyze changes in the chemical environment of the guanine thin films as a function of ion fluence. Direct comparison of the secondary ion and neutral components of the molecular depth profiles yields valuable information about chemical damage accumulation as well as changes in the molecular ionization probability. An analytical protocol based on the erosion dynamics model is developed and evaluated using guanine and trehalose molecular secondary ion signals with and without comparable laser photoionization data. PMID- 26269661 TI - Adaptive Confidence Bands for Nonparametric Regression Functions. AB - A new formulation for the construction of adaptive confidence bands in non parametric function estimation problems is proposed. Confidence bands are constructed which have size that adapts to the smoothness of the function while guaranteeing that both the relative excess mass of the function lying outside the band and the measure of the set of points where the function lies outside the band are small. It is shown that the bands adapt over a maximum range of Lipschitz classes. The adaptive confidence band can be easily implemented in standard statistical software with wavelet support. Numerical performance of the procedure is investigated using both simulated and real datasets. The numerical results agree well with the theoretical analysis. The procedure can be easily modified and used for other nonparametric function estimation models. PMID- 26269662 TI - Situational interest, cognitive engagement, and achievement in physical education. AB - Students' learning has been the center of schooling. This study examined the contribution of situational interest motivation and cognitive engagement in workbooks to student achievement in learning health-related fitness knowledge. Situational interest, performance on solving workbook problems, and knowledge gain in cardio-respiratory fitness and benefits were measured in 670 third-grade students from 13 randomly selected urban elementary schools. Structural equation modeling and regression curve estimation analyses revealed that situational interest contributed little to workbook performance and knowledge gain. Performance on solving workbook problems contributed significantly to knowledge gain. The results also show that skipping workbook tasks had stronger negative impact on knowledge gain than performing the tasks incorrectly, suggesting the importance of engaging students in the learning process by attempting the workbook tasks. The findings reinforced the value of using workbooks to facilitate cognitive knowledge learning in physical education, but raised questions about the direct function of situational interest on engaging students in cognitive learning. PMID- 26269663 TI - Traditional, modern or mixed? Perspectives on social, economic, and health impacts of evolving food retail in Thailand. AB - Transnational food retailers expanded to middle-income countries over recent decades responding to supply (liberalized foreign investment) and demand (rising incomes, urbanization, female workforce participation, and time poverty). Control in new markets diffuses along three axes: socio-economic (rich to poor), geographic (urban to rural), and product category (processed foods to fresh foods). We used a mixed method approach to study the progression of modern retail in Thailand on these three axes and consumer preferences for food retailing. In Thailand modern retail controls half the food sales but traditional fresh markets remain important. Quantitative questionnaires administered to members of a large national cohort study revealed around half of respondents were primarily traditional shoppers and half either utilized modern and traditional formats equally or primarily shopped at supermarkets. Fresh foods were mainly purchased at traditional retail formats and dry packaged foods at supermarkets. Qualitative interviews found price and quality of produce and availability of culturally important products to be significant reasons for continued support of fresh markets. Our results show socio-economic and geographic diffusion is already advanced with most respondents having access to and utilizing modern retail. Control of the fresh food sector by transnationals faces barriers in Thailand and may remain elusive. The short to mid-term outcome may be a bifurcated food system with modern and traditional retail each retaining market share, but fresh markets longer term survival may require government assistance as supermarkets become more established. Fresh markets supply affordable, healthy foods, and livelihoods for poorer Thais and are repositories of Thai food culture and social networks. If they survive they will confer cultural, social, economic, and health benefits. PMID- 26269664 TI - Inflammatory pouch disease: The spectrum of pouchitis. AB - Restorative proctocolectomy with ileal-pouch anal anastomosis (IPAA) is the operation of choice for medically refractory ulcerative colitis (UC), for UC with dysplasia, and for familial adenomatous polyposis (FAP). IPAA can be a treatment option for selected patients with Crohn's colitis without perianal and/or small bowel disease. The term "pouchitis" refers to nonspecific inflammation of the pouch and is a common complication in patients with IPAA; it occurs more often in UC patients than in FAP patients. This suggests that the pathogenetic background of UC may contribute significantly to the development of pouchitis. The symptoms of pouchitis are many, and can include increased bowel frequency, urgency, tenesmus, incontinence, nocturnal seepage, rectal bleeding, abdominal cramps, and pelvic discomfort. The diagnosis of pouchitis is based on the presence of symptoms together with endoscopic and histological evidence of inflammation of the pouch. However, "pouchitis" is a general term representing a wide spectrum of diseases and conditions, which can emerge in the pouch. Based on the etiology we can sub-divide pouchitis into 2 groups: idiopathic and secondary. In idiopathic pouchitis the etiology and pathogenesis are still unclear, while in secondary pouchitis there is an association with a specific causative or pathogenetic factor. Secondary pouchitis can occur in up to 30% of cases and can be classified as infectious, ischemic, non-steroidal anti-inflammatory drugs-induced, collagenous, autoimmune-associated, or Crohn's disease. Sometimes, cuffitis or irritable pouch syndrome can be misdiagnosed as pouchitis. Furthermore, idiopathic pouchitis itself can be sub-classified into types based on the clinical pattern, presentation, and responsiveness to antibiotic treatment. Treatment differs among the various forms of pouchitis. Therefore, it is important to establish the correct diagnosis in order to select the appropriate treatment and further management. In this editorial, we present the spectrum of pouchitis and the specific features related to the diagnosis and treatment of the various forms. PMID- 26269666 TI - Clinical applications of 5-aminolevulinic acid-mediated fluorescence for gastric cancer. AB - 5-aminolevulinic acid (ALA) is a naturally occurring amino acid that is a protoporphyrin IX (PpIX) precursor and a next-generation photosensitive substance. After exogenous administration of ALA, PpIX specifically accumulates in cancer cells owing to the impaired metabolism of ALA to PpIX in mitochondria, which results in a red fluorescence following irradiation with blue light and the formation of singlet oxygen. Fluorescence navigation by photodynamic diagnosis (PDD) using ALA provides good visualization and detection of gastric cancer lesions and is a potentially valuable diagnostic tool for gastric cancer for evaluating both the surgical resection margins and extension of the lesion. Furthermore, PDD using ALA might be used to detect peritoneal metastases during preoperative staging laparoscopy, where it could provide useful information for the selection of a therapeutic approach. Another promising application for this modality is in the evaluation of lymph node metastases. Photodynamic therapy (PDT) using ALA to cause selective damage based on the accumulation of a photosensitizer in malignant tissue is expected to be a non-invasive endoscopic treatment for superficial early gastric cancer. ALA has the potential to be used not only as a diagnostic agent but also as a therapeutic drug, resulting in a new strategy for cancer diagnosis and therapy. Here, we review the current use of PDD and PDT in gastric cancer and evaluate its future potential beyond conventional modalities combined with a light energy upconverter, a light-emitting diode and near-infrared rays as light sources. PMID- 26269665 TI - Neoplastic disease after liver transplantation: Focus on de novo neoplasms. AB - De novo neoplasms account for almost 30% of deaths 10 years after liver transplantation and are the most common cause of mortality in patients surviving at least 1 year after transplant. The risk of malignancy is two to four times higher in transplant recipients than in an age- and sex-matched population, and cancer is expected to surpass cardiovascular complications as the primary cause of death in transplanted patients within the next 2 decades. Since exposure to immunosuppression is associated with an increased frequency of developing neoplasm, long-term immunosuppression should be therefore minimized. Promising results in the prevention of hepatocellular carcinoma (HCC) recurrence have been reported with the use of mTOR inhibitors including everolimus and sirolimus and the ongoing open-label prospective randomized controlled SILVER. Study will provide more information on whether sirolimus-containing vs mTOR-inhibitor-free immunosuppression is more efficacious in reducing HCC recurrence. PMID- 26269667 TI - Advances in refractory ulcerative colitis treatment: A new therapeutic target, Annexin A2. AB - Medical treatment has progressed significantly over the past decade towards achieving and maintaining clinical remission in patients with refractory ulcerative colitis (UC). Proposed mediators of inflammation in UC include pro inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-2, and the cell-surface adhesive molecule integrin alpha4beta7. Conventional therapeutics for active UC include 5-aminosalicylic acid, corticosteroids and purine analogues (azathioprine and 6-mercaptopurine). Patients who fail to respond to conventional therapy are treated with agents such as the calicineurin inhibitors cyclosporine and tacrolimus, the TNF-alpha inhibitors infliximab or adalimumab, or a neutralizing antibody (vedolizumab) directed against integrin alpha4beta7. These therapeutic agents are of benefit for patients with refractory UC, but are not universally effective. Our recent research on TNF-alpha shedding demonstrated that inhibition of annexin (ANX) A2 may be a new therapeutic strategy for the prevention of TNF-alpha shedding during inflammatory bowel disease (IBD) inflammation. In this review, we provide an overview of therapeutic treatments that are effective and currently available for UC patients, as well as some that are likely to be available in the near future. We also propose the potential of ANX A2 as a new molecular target for IBD treatment. PMID- 26269670 TI - Chemotherapy beyond second-line in advanced gastric cancer. AB - Patients with advanced gastric cancer (AGC) can be treated with multiple lines of chemotherapy. Although several randomized trials have demonstrated the benefit of second-line chemotherapy compared with best supportive care, there is no evidence that further lines of chemotherapy will result in substantial prolongation of survival. Despite this, the practice of offering chemotherapy beyond second-line agents to AGC patients is not uncommon if their performance status is well preserved and they are willing to receive subsequent active treatments. The choice of chemotherapeutic agents depends on the patient's prior regimens. However, there are important controversial issues in the salvage setting of AGC, including a subset of patients who may benefit from chemotherapy, that still remain unanswered. This report reviews the available evidence regarding the impact of third- and subsequent lines of chemotherapy on survival and quality of life in patients with AGC. PMID- 26269669 TI - Microscopic colitis: A review of etiology, treatment and refractory disease. AB - Microscopic colitis is a common cause of chronic, nonbloody diarrhea. Microscopic colitis is more common in women than men and usually affects patients in their sixth and seventh decade. This article reviews the etiology and medical management of microscopic colitis. The etiology of microscopic colitis is unknown, but it is associated with autoimmune disorders, such as celiac disease, polyarthritis, and thyroid disorders. Smoking has been identified as a risk factor of microscopic colitis. Exposure to medications, such as non-steroidal anti-inflammatory drugs, proton pump inhibitors, and selective serotonin reuptake inhibitors, is suspected to play a role in microscopic colitis, although their direct causal relationship has not been proven. Multiple medications, including corticosteroids, anti-diarrheals, cholestyramine, bismuth, 5-aminosalicylates, and immunomodulators, have been used to treat microscopic colitis with variable response rates. Budesonide is effective in inducing and maintaining clinical remission but relapse rate is as high as 82% when budesonide is discontinued. There is limited data on management of steroid-dependent microscopic colitis or refractory microscopic colitis. Immunomodulators seem to have low response rate 0%-56% for patients with refractory microscopic colitis. Response rate 66%-100% was observed for use of anti-tumor necrosis factor (TNF) therapy for refractory microscopic colitis. Anti-TNF and diverting ileostomy may be an option in severe or refractory microscopic colitis. PMID- 26269668 TI - Role of the normal gut microbiota. AB - Relation between the gut microbiota and human health is being increasingly recognised. It is now well established that a healthy gut flora is largely responsible for overall health of the host. The normal human gut microbiota comprises of two major phyla, namely Bacteroidetes and Firmicutes. Though the gut microbiota in an infant appears haphazard, it starts resembling the adult flora by the age of 3 years. Nevertheless, there exist temporal and spatial variations in the microbial distribution from esophagus to the rectum all along the individual's life span. Developments in genome sequencing technologies and bioinformatics have now enabled scientists to study these microorganisms and their function and microbe-host interactions in an elaborate manner both in health and disease. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Several factors play a role in shaping the normal gut microbiota. They include (1) the mode of delivery (vaginal or caesarean); (2) diet during infancy (breast milk or formula feeds) and adulthood (vegan based or meat based); and (3) use of antibiotics or antibiotic like molecules that are derived from the environment or the gut commensal community. A major concern of antibiotic use is the long-term alteration of the normal healthy gut microbiota and horizontal transfer of resistance genes that could result in reservoir of organisms with a multidrug resistant gene pool. PMID- 26269671 TI - Expression of renal Oat5 and NaDC1 transporters in rats with acute biliary obstruction. AB - AIM: To examine renal expression of organic anion transporter 5 (Oat5) and sodium dicarboxylate cotransporter 1 (NaDC1), and excretion of citrate in rats with acute extrahepatic cholestasis. METHODS: Obstructive jaundice was induced in rats by double ligation and division of the common bile duct (BDL group). Controls underwent sham operation that consisted of exposure, but not ligation, of the common bile duct (Sham group). Studies were performed 21 h after surgery. During this period, animals were maintained in metabolic cages in order to collect urine. The urinary volume was determined by gravimetry. The day of the experiment, blood samples were withdrawn and used to measure total and direct bilirubin as indicative parameters of hepatic function. Serum and urine samples were used for biochemical determinations. Immunoblotting for Oat5 and NaDC1 were performed in renal homogenates and brush border membranes from Sham and BDL rats. Immunohistochemistry studies were performed in kidneys from both experimental groups. Total RNA was extracted from rat renal tissue in order to perform reverse transcription polymerase chain reaction. Another set of experimental animals were used to evaluate medullar renal blood flow (mRBF) using fluorescent microspheres. RESULTS: Total and direct bilirubin levels were significantly higher in BDL animals, attesting to the adequacy of biliary obstruction. An important increase in mRBF was determined in BDL group (Sham: 0.53 +/- 0.12 mL/min per 100 g body weight vs BDL: 1.58 +/- 0.24 mL/min per 100 g body weight, P < 0.05). An increase in the urinary volume was observed in BDL animals. An important decrease in urinary levels of citrate was seen in BDL group. Besides, a decrease in urinary citrate excretion (Sham: 0.53 +/- 0.11 g/g creatinine vs BDL: 0.07 +/- 0.02 g/g creatinine, P < 0.05) and an increase in urinary excretion of H(+) (Sham: 0.082 +/- 0.03 MUmol/g creatinine vs BDL: 0.21 +/- 0.04 MUmol/g creatinine, P < 0.05) were observed in BDL animals. We found upregulations of both proteins Oat5 and NaDC1 in brush border membranes where they are functional. Immunohistochemistry technique corroborated these results for both proteins. No modifications were observed in Oat5 mRNA and in NaDC1 mRNA levels in kidney from BDL group as compared with Sham ones. CONCLUSION: Citrate excretion is decreased in BDL rats, at least in part, because of the higher NaDC1 expression. Using the outward gradient of citrate generated by NaDC1, Oat5 can reabsorb/eliminate different organic anions of pathophysiological importance. PMID- 26269672 TI - Brewers' rice modulates oxidative stress in azoxymethane-mediated colon carcinogenesis in rats. AB - AIM: To investigate the mechanistic action of brewers' rice in regulating the Wnt/nuclear factor-kappa B (NF-kappaB)/Nrf2-signaling pathways during colon carcinogenesis in male Sprague-Dawley rats. METHODS: Male Sprague-Dawley rats were randomly divided into the following five groups (six rats in each group): (G1) normal, (G2) azoxymethane (AOM) alone, (G3) AOM + 10% (weight (w)/weight (w)) brewers' rice, (G4) AOM + 20% (w/w) brewers' rice, and (G5) AOM + 40% (w/w) brewers' rice. They were intraperitoneally administered 15 mg/kg body weight of AOM in saline once weekly over a two-week period and treated with an American Institute of Nutrition (AIN)-93G diet containing 10%, 20%, and 40% (w/w) brewers' rice. The mRNA levels of glycogen synthase kinase 3beta (GSK3beta), beta-catenin, key inflammation markers, nuclear factor E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1)-dependent transcriptional activity were assessed by quantitative real-time polymerase chain reaction analyses. The colon superoxide dismutase, malondialdehyde, and nitric oxide levels were also analyzed to assess the antioxidant effect of these treatments. The results were analyzed using one way analysis of variance (ANOVA), and a P value of < 0.05 was considered significant. RESULTS: The overall analyses demonstrated that the dietary administration of brewers' rice in AOM-induced rat colon carcinogenesis resulted in the transcriptional upregulation of GSK3beta, inducible nitric oxide synthase (iNOS), Nrf2, and HO-1. We discovered that the dietary administration of brewers' rice downregulated the beta-catenin and NF-kappaB mRNA levels. A significant reduction in beta-catenin expression was found in the groups administered with 20% (0.611 +/- 0.034) and 40% (0.436 +/- 0.045) (w/w) brewers' rice compared with that of the group treated with AOM alone (1.000 +/- 0.064) (P < 0.05). The NF kappaB expression was significantly lower between the AOM-alone group (1.000 +/- 0.048) and those groups fed with diets containing 10% (w/w) brewers' rice (0.255 +/- 0.022), 20% (w/w) brewers' rice (0.450 +/- 0.045), or 40% (w/w) brewers' rice (0.541 +/- 0.027) (P < 0.05). Brewers' rice improved the antioxidant levels, indicating that brewers' rice can enhance effective recovery from oxidative stress induced by AOM. CONCLUSION: Our results provide evidence that brewers' rice can suppress colon cancer via the regulation of Nrf2 expression and the inhibition of the Wnt/NF-kappaB signaling pathways. PMID- 26269673 TI - Upregulation of nemo-like kinase is an independent prognostic factor in colorectal cancer. AB - AIM: To investigate the expression and oncogenic role of nemo-like kinase (NLK) in colorectal cancer. METHODS: Expression of NLK protein was assessed by immunohistochemistry in tissue specimens from 56 cases of normal colorectal mucosa, 51 cases of colorectal adenoma, and 712 cases of colorectal cancer. In addition, NLK expression was knocked down using a lentivirus carrying NLK small hairpin RNA in colorectal cancer cells. Cell viability methylthiazoletetrazolium assays, colony formation assays, flow cytometry cell cycle assays, Transwell migration assays, and gene expression assays were performed to explore its role on proliferation and migration of colorectal cancer. RESULTS: Expression of NLK protein progressively increased in tissues from the normal mucosa through adenoma to various stages of colorectal cancer. Overexpression of NLK protein was associated with advanced tumor-lymph node-metastasis stages, poor differentiation, lymph node and distant metastases, and a higher recurrence rate of colorectal cancer (P < 0.05). Multivariate analyses showed that NLK expression was an independent prognostic factor to predict overall survival (hazard ratio 2.57, 95% confidence interval: 1.66-3.98; P < 0.001) and disease-free survival (hazard ratio 1.96, 95% confidence interval: 1.40-2.74: P < 0.001) of colorectal cancer patients. Furthermore, knockdown of NLK expression in colorectal cancer cell lines reduced cell viability, colony formation, and migration, and arrested tumor cells at the G0/G1 phase of the cell cycle. At the gene level, knockdown of NLK expression inhibited matrix metalloproteinase-2 expression in colorectal cancer cells. CONCLUSION: NLK overexpression is an independent prognostic factor in colorectal cancer and knockdown of NLK expression inhibits colorectal cancer progression and metastasis. PMID- 26269674 TI - Influence of perfusate on liver viability during hypothermic machine perfusion. AB - AIM: To optimize the perfusates used for hypothermic machine perfusion (HMP). METHODS: Sprague-Dawley rats were assigned randomly to three groups (n = 12 per group) that received either saline, University of Wisconsin cold-storage solution (UW) or histidine-tryptophan-ketoglutarate solution (HTK) as the perfusate. Each group was divided into two subgroups: static cold storage (SCS) and HMP (n = 6 per subgroup). The liver graft was retrieved according to the method described by Kamada. For the SCS group, the graft was directly placed into cold perfusate (0-4 degrees C) for 6 h after liver isolation while the portal vein of the graft was connected to the perfusion machine for the HMP group. Then the perfusates were collected at different time points for analysis of aspartate aminotransferase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) levels. Liver tissues were obtained for evaluation of histology, dry/wet weight (D/W) ratio, and malondialdehyde (MDA) and adenosine-triphosphate (ATP) levels. The portal vein pressure and velocity were monitored in real time in all HMP subgroups. RESULTS: Comparison of HMP and SCS: Regardless of the perfusate, HMP improved the architecture of donor graft in reducing the congestion around sinusoids and central vein and maintaining sinusoid lining in morphology; HMP improved liver function in terms of ALT, AST and LDH, especially during the 3-6 h period (SCS vs HMP using saline: ALT3, 225.00 +/- 105.62 vs 49.50 +/- 18.50, P = 0.047; LDH3, 1362.17 +/- 563.30 vs 325.75 +/- 147.43, P = 0.041; UW: LDH6, 2880.14 +/- 948.46 vs 2135.00 +/- 174.27, P = 0.049; HTK, AST6, 307.50 +/- 52.95 vs 185.20 +/- 20.46, P = 0.041); HMP decreased MDA level (saline, 2.79 +/- 0.30 vs 1.09 +/- 0.09, P = 0.008; UW, 3.01 +/- 0.77 vs 1.23 +/- 0.68, P = 0.005; HTK, 3.30 +/- 0.52 vs 1.56 +/- 0.22, P = 0.006). Comparison among HMP subgroups: HTK showed less portal vein resistance than UW and saline (vs saline, 3.41 +/- 0.49 vs 5.00 +/- 0.38, P < 0.001; vs UW, 3.41 +/- 0.49 vs 4.52 +/- 0.63, P = 0.007); UW reduced edema most efficiently (vs saline, 0.68 +/- 0.02 vs 0.79 +/- 0.05, P = 0.013), while HTK maintained ATP levels best (vs saline, 622.60 +/- 29.11 vs 327.43 +/- 44.66, P < 0.001; vs UW, 622.60 +/- 29.11 vs 301.80 +/- 37.68, P < 0.001). CONCLUSION: HMP is superior to SCS in maintaining both architecture and function of liver grafts. Further, HTK was found to be the optimal perfusate for HMP. PMID- 26269675 TI - Overexpression of pim-3 and protective role in lipopolysaccharide-stimulated hepatic stellate cells. AB - AIM: To investigate pim-3 expression in hepatic stellate cells (HSCs) stimulated by lipopolysaccharide (LPS), and its protective effect on HSCs. METHODS: Rat HSC T6 cells were stimulated by LPS. The effect of LPS on proliferation and apoptosis of HSC-T6 cells was investigated by methyl thiazoyltetrazolium (MTT) assay and flow cytometry after annexin V-fluorescein isothiocyanate/propidium iodide double staining. pim-3 mRNA and protein were detected by reverse transcriptase polymerase chain reaction and Western blotting at 48 h when HSC-T6 cells were stimulated with 1 MUg/mL LPS for 0, 3, 6, 12, 24 and 48 h. The cells without stimulation served as controls. To study the effect of pim-3 kinase on HSC-T6 cells, si-pim3 (siRNA against pim-3) was transfected into HSC-T6 cells. HSC-T6 cells were subjected to different treatments, including LPS, si-pim3, or si-pim3 plus LPS, and control cells were untreated. Protein expression of pim-3 was detected at 48 h after treatment, and cell proliferation at 24 and 48 h by MTT assay. Apoptosis was detected by flow cytometry, and confirmed with caspase-3 activity assay. RESULTS: LPS promoted HSC-T6 cell proliferation and protected against apoptosis. Significantly delayed upregulation of pim-3 expression induced by LPS occurred at 24 and 48 h for mRNA expression (pim-3/beta-actin RNA, 24 or 48 h vs 0 h, 0.81 +/- 0.20 or 0.78 +/- 0.21 vs 0.42 +/- 0.13, P < 0.05), and occurred at 12 h and peaked at 24 and 48 h for protein expression (pim-3/GAPDH protein, 12, or 24 or 48 h vs 0 h, 0.68 +/- 0.12, 1.47 +/- 0.25 or 1.51 +/- 0.23 vs 0.34 +/- 0.04, P < 0.01). pim-3 protein was ablated by si-pim3 and upregulated by LPS in HSC-T6 cells at 48 h after treatment (pim-3/GAPDH: si-pim3, si-pim3 plus LPS or LPS vs control, 0.11 +/- 0.05, 0.12 +/- 0.05 or 1.08 +/- 0.02 vs 0.39 +/- 0.03, P < 0.01). Ablation of pim-3 by si-pim3 in HSC-T6 cells partly abolished proliferation (OD at 24 h, si-pim3 group or si-pim3 plus LPS vs control, 0.2987 +/- 0.050 or 0.4063 +/- 0.051 vs 0.5267 +/- 0.030, P < 0.01; at 48 h 0.4634 +/- 0.056 or 0.5433 +/- 0.031 vs 0.8435 +/- 0.028, P < 0.01; si-pim3 group vs si-pim3 plus LPS, P < 0.01 at 24 h and P < 0.05 at 48 h), and overexpression of pim-3 in the LPS group increased cell proliferation (OD: LPS vs control, at 24 h, 0.7435 +/- 0.028 vs 0.5267 +/- 0.030, P < 0.01; at 48 h, 1.2136 +/- 0.048 vs 0.8435 +/- 0.028, P < 0.01). Ablation of pim3 with si-pim3 in HSC-T6 cells aggravated apoptosis (si-pim3 or si-pim3 plus LPS vs control, 42.3% +/- 1.1% or 40.6% +/- 1.3% vs 16.8% +/- 3.3%, P < 0.01; si-pim3 vs si-pim3 plus LPS, P > 0.05), and overexpression of pim-3 in the LPS group attenuated apoptosis (LPS vs control, 7.32% +/- 2.1% vs 16.8% +/- 3.3%, P < 0.05). These results were confirmed by caspase-3 activity assay. CONCLUSION: Overexpression of pim-3 plays a protective role in LPS-stimulated HSC-T6 cells. PMID- 26269676 TI - Circulating levels of vitamin D and colorectal adenoma: A case-control study and a meta-analysis. AB - AIM: To examine the association between circulating 25-hydroxyvitamin D [25(OH)D] levels and colorectal adenoma in a case-control study and a meta-analysis. METHODS: We conducted a matched case-control study (112 cases and 112 matched controls) and combined 15 studies, including our study, in a meta-analysis. The study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using a random-effects model. In total, 5454 colorectal adenomas and 6656 controls were included in the meta-analysis. RESULTS: In a meta-analysis including 14 previous studies and our study, we observed a significant inverse association between circulating 25(OH)D levels and colorectal adenoma (OR = 0.68; 95%CI: 0.54-0.82) when comparing the highest category with the lowest category. Stratification by adenoma location (proximal or distal adenoma) showed similar estimates. When we stratified by study region, the ORs (95%CIs) were 0.70 (0.52 0.88) in the US and 0.66 (0.34-0.97) in Asia. CONCLUSION: These data suggest an inverse association between circulating 25(OH)D levels and colorectal adenoma in both Western and Asian populations. PMID- 26269677 TI - Value of two-phase dynamic multidetector computed tomography in differential diagnosis of post-inflammatory strictures from esophageal cancer. AB - AIM: To characterize the computed tomography (CT) findings in patients with post inflammatory esophageal strictures (corrosive and peptic) and reveal the optimal scanning phase protocols for distinguishing post-inflammatory esophageal stricture and esophageal cancer. METHODS: Sixty-five patients with esophageal strictures of different etiology were included in this study: 24 patients with 27 histopathologically confirmed corrosive strictures, 10 patients with 12 peptic strictures and 31 patients with esophageal cancer were evaluated with a two-phase dynamic contrast-enhanced MDCT. Arterial and venous phases at 10 and 35 s after the attenuation of 200 HU were obtained at the descending aorta, with a delayed phase at 6-8 min after the start of injection of contrast media. For qualitative analysis, CT scans of benign strictures were reviewed for the presence/absence of the following features: "target sign", luminal mass, homogeneity of contrast medium uptake, concentric wall thickening, conically shaped suprastenotic dilatation, smooth boundaries of stenosis and smooth mucous membrane at the transition to stenosis, which were compared with a control group of 31 patients who had esophageal cancer. The quantitative analysis included densitometric parameter acquisition using regions-of-interest measurement of the zone of stenosis and normal esophageal wall and the difference between those measurements (DeltaCT) at all phases of bolus contrast enhancement. Esophageal wall thickening, length of esophageal wall thickening and size of the regional lymph nodes were also evaluated. RESULTS: The presence of a concentric esophageal wall, conically shaped suprastenotic dilatation, smooth upper and lower boundaries, "target sign" and smooth mucous membrane at the transition to stenosis were suggestive of a benign cause, with sensitivities of 92.31%, 87.17%, 94.87%, 76.92% and 82.05%, respectively, and specificities of 70.96%, 89.66%, 80.65%, 96.77% and 93.55%, respectively. The features that were most suggestive of a malignant cause were eccentric esophageal wall thickening, tuberous upper and lower boundaries of stenosis, absence of mucous membrane visualization, rupture of the mucous membrane at the upper boundary of stenosis, cup-shaped suprastenotic dilatation, luminal mass and enlarged regional lymph nodes with specificities of 92.31% 94.87%, 67.86%, 100%, 97.44%, 94.87% and 82.86%, respectively and sensitivities of 70.97%, 80.65%, 96.77%, 80.65%, 54.84%, 87.10% and 60%, respectively. The highest tumor attenuation occurred in the arterial phase (mean attenuation 74.13 +/- 17.42 HU), and the mean attenuation difference between the tumor and the normal esophageal wall (mean DeltaCT) in the arterial phase was 23.86 +/- 19.31 HU. Here, 11.5 HU of DeltaCT in the arterial phase was the cut-off value used to differentiate esophageal cancer from post-inflammatory stricture (P = 0.000). The highest attenuation of post-inflammatory strictures occurred in the delayed phase (mean attenuation 71.66 +/- 14.28 HU), and the mean DeltaCT in delayed phase was 34.03 +/- 15.94 HU. Here, 18.5 HU of DeltaCT in delayed phase was the cut-off value used to differentiate post-inflammatory stricture from esophageal cancer (P < 0.0001). CONCLUSION: The described imaging findings reveal high diagnostic significance in the differentiation of benign strictures from esophageal cancer. PMID- 26269678 TI - Transcatheter arterial infusion for advanced hepatocellular carcinoma: Who are candidates? AB - AIM: To elucidate anticancer effects of transcatheter arterial infusion chemotherapy (TAI) in patients with hepatocellular carcinoma (HCC). METHODS: Data from a total of 95 patients with HCC who received TAI were analyzed retrospectively. The efficacy of TAI was evaluated according to the Response Evaluation Criteria in Cancer of the Liver. Overall survival was calculated from the date of initial treatment to the date of death or last follow-up. Survival curves were calculated by the Kaplan-Meier method, and differences in survival were evaluated by the log rank test. Clinical variables that were identified as statistically different by a univariate analysis were included into the Cox proportional hazard regression model for multivariate analysis. A prognostic index based on the regression coefficients derived from variables identified by the multivariate analysis was constructed. Stratification of the patients was conducted using this prognostic index. RESULTS: The patient group was comprised of 76 men and 19 women with an average age of 68 years (range: 37-82 years). Six patients (6.3%) showed complete response and 18 patients (18.9%) showed partial response, for an overall response rate of 25.2%. The median overall survival was 27.6 mo, and the proportions of survivors at 1, 2, and 5 years were 67.4%, 54.0%, and 17.4%, respectively. Multivariate analysis demonstrated that no prior transcatheter arterial chemoembolization, lactate dehydrogenase < 230 IU/L, and performance status of 0 were the independent favorable prognostic factors. The development of a 0-3-point prognostic score index was based on the sum of these three prognostic factors. Subsequently, the patients were categorized into three groups: those with a good (prognostic index = 0-1; n = 54), intermediate (prognostic index = 2; n = 26), or poor (prognostic index = 3; n = 15) prognosis. The median survival times in these three groups were 41.0, 21.2, and 6.8 mo, respectively (P < 0.01). CONCLUSION: Our simple prognostic index may be helpful for management of patients in determining treatment strategies for advanced HCC in the era of molecularly targeted therapy. PMID- 26269679 TI - Reversed portal flow: Clinical influence on the long-term outcomes in cirrhosis. AB - AIM: To elucidate the natural history and the longitudinal outcomes in cirrhotic patients with non-forward portal flow (NFPF). METHODS: The present retrospective study consisted of 222 cirrhotic patients (120 males and 102 females; age, 61.7 +/- 11.1 years). The portal hemodynamics were evaluated at baseline and during the observation period using both pulsed and color Doppler ultrasonography. The diameter (mm), flow direction, mean flow velocity (cm/s), and mean flow volume (mL/min) were assessed at the portal trunk, the splenic vein, the superior mesenteric vein, and the collateral vessels. The average values from 2 to 4 measurements were used for the data analysis. The portal flow direction was defined as follows: forward portal flow (FPF) for continuous hepatopetal flow; bidirectional flow for to-and-fro flow; and reversed flow for continuous hepatofugal flow. The bidirectional flow and the reversed flow were classified as NFPF in this study. The clinical findings and prognosis were compared between the patients with FPF and those with NFPF. The median follow-up period was 40.9 mo (range, 0.3-156.5 mo). RESULTS: Twenty-four patients (10.8%) demonstrated NFPF, accompanied by lower albumin level, worse Child-Pugh scores, and model for end stage liver disease scores. The portal hemodynamic features in the patients with NFPF were smaller diameter of the portal trunk; presence of short gastric vein, splenorenal shunt, or inferior mesenteric vein; and advanced collateral vessels (diameter > 8.7 mm, flow velocity > 10.2 cm/s, and flow volume > 310 mL/min). The cumulative incidence rates of NFPF were 6.5% at 1 year, 14.5% at 3 years, and 23.1% at 5 years. The collateral vessels characterized by flow velocity > 9.5 cm/s and those located at the splenic hilum were significant predictive factors for developing NFPF. The cumulative survival rate was significantly lower in the patients with NFPF (72.2% at 1 year, 38.5% at 3 years, 38.5% at 5 years) than in those with forward portal flow (84.0% at 1 year, 67.8% at 3 years, 54.3% at 5 years, P = 0.0123) using the Child-Pugh B and C classifications. CONCLUSION: NFPF has a significant negative effect on the prognosis of patients with worse liver function reserve, suggesting the need for careful management. PMID- 26269680 TI - Clinical outcomes and ergonomics analysis of three laparoscopic techniques for Hirschsprung's disease. AB - AIM: To report the clinical outcomes and ergonomics analysis of three laparoscopic approaches in the management of Hirschsprung's disease (HD). METHODS: There were 90 pediatric patients (63 boys, 27 girls; mean age: 3.6 +/- 2.7 mo; range: 1.0-90.2 mo) who underwent laparoscopic endorectal pull-through Soave procedures for short- and long-segment HD in our hospital. Three laparoscopic approaches were used: conventional laparoscopic pull-through (CLP) in 30 patients between 2009 and 2013, single-incision laparoscopic pull-through (SILP) in 28 patients between 2010 and 2013, and hybrid single-incision laparoscopic pull-through (H-SILP) in 32 patients between 2011 and 2013. We applied the hybrid version of the single-incision approach in 2011 to preserve the cosmetic advantage of SILP and the ergonomic advantage of CLP. We retrospectively analyzed the clinical data, cosmetic results, and ergonomics of these three approaches to have a better understanding of the selection of one approach over another. RESULTS: The CLP, SILP, and H-SILP groups were similar in regard to age, sex, transition zone, blood loss, hospital stay, and intraoperative complications. Early and late postoperative results were not different, with equal daily defecation frequency and postoperative complications. No conversion to open technique was needed and none of the patients had recurrent constipation. With proper training, the ergonomics challenges were overcome and similar operative times were registered for the general operative time in the patients < 1 year of age and the short-segment HD patients. However, significantly shorter operative times were registered compared to SILP for patients > 1 year of age (CLP and H-SILP: 120 +/- 15 min and 119 +/- 12 min, respectively, vs 140 +/- 7 min; P < 0.05) and for long-segment HD patients (152 +/- 3.5 min and 154 +/- 3.6 min, respectively, vs 176 +/- 2.3 min; P < 0.05). The best cosmetic result was registered with the SILP (scarless), followed by the H SILP (near scarless appearance) and the CLP (visible scars) procedures. CONCLUSION: Based on the results, we believed that the laparoscopic approach should be selected according to the age, transition zone, and desired cosmetic result. PMID- 26269681 TI - Helicobacter pylori infection is associated with gallstones: Epidemiological survey in China. AB - AIM: To elucidate the prevalence and risk factors for gallstones, primarily focusing on Helicobacter pylori (H. pylori) infection. METHODS: A total of 10016 Chinese subjects, who had undergone physical examination, fasting (13)C urea breath test and abdominal ultrasonography, had sufficient blood test data, and had finished a questionnaire, were included in this cross-sectional study. Participants (n = 1122) who had previous eradication of H. pylori were studied separately. RESULTS: Gallstones were discovered in 9.10% of men and 8.58% of women, with no significant sex difference. Multivariate analyses displayed that age, aspartate aminotransferase, total cholesterol, H. pylori infection, hepatitis C virus (HCV) infection, and fatty liver had a significant association with gallstones (P < 0.05). Successive multiple logistic regression analysis including index of odds ratio (OR) and standardized coefficient (beta) indicated that older age (OR/beta = 1.056/0.055), H. pylori infection (OR/beta = 1.454/0.109), HCV infection (OR/beta = 1.871/0.123), and fatty liver (OR/beta = 1.947/0.189) had a significant positive association with gallstones. After age stratification, H. pylori infection and fatty liver still had a significant positive association with gallstones in any age-specific groups, whereas HCV infection had a significant positive association in patients aged > 40 years. The prevalence of gallstones among H. pylori-positive, H. pylori-eradicated, and H. pylori-negative subjects was 9.47%, 9.02%, and 8.46%, respectively. The matched analysis showed that gallstones among H. pylori eradicated subjects was significantly lower compared with H. pylori-positive subjects (P < 0.05). CONCLUSION: H. pylori infection and fatty liver have a significant positive association with gallstones. H. pylori eradication may lead to prevention of gallstones. PMID- 26269682 TI - Viral hepatitis prevalence in patients with active and latent tuberculosis. AB - AIM: To assess the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and association with drug induced liver injury (DILI) in patients undergoing anti-tuberculosis (TB) therapy. METHODS: Four hundred and twenty nine patients with newly diagnosed TB - either active disease or latent infection - who were due to commence anti-TB therapy between September 2008 and May 2011 were included. These patients were prospectively tested for serological markers of HBV, HCV and human immunodeficiency virus (HIV) infections - hepatitis B core antigen (HBcAg), hepatitis B surface antigen (HBsAg), hepatitis B e antigen, IgG and IgM antibody to HBcAg (anti-HBc), HCV IgG antibody and HIV antibody using a combination of enzyme-linked immunosorbent assay, Western blot assay and polymerase chain reaction techniques. Patients were reviewed at least monthly during the TB treatment initiation phase. Liver function tests were measured prior to commencement of anti-TB therapy and 2-4 wk later. Liver function tests were also performed at any time the patient had significant nausea, vomiting, rash, or felt non-specifically unwell. Fisher's exact test was used to measure significance in comparisons of proportions between groups. A P value of less than 0.05 was considered statistically significant. RESULTS: Of the 429 patients, 270 (62.9%) had active TB disease and 159 (37.1%) had latent TB infection. 61 (14.2%) patients had isolated anti-HBc positivity, 11 (2.6%) were also HBsAg positive and 7 (1.6%) were HCV-antibody positive. 16/270 patients with active TB disease compared to 2/159 patients with latent TB infection had markers of chronic viral hepatitis (HBsAg or HCV antibody positive; P = 0.023). Similarly the proportion of HBsAg positive patients were significantly greater in the active vs latent TB infection group (10/43 vs 1/29, P = 0.04). The prevalence of chronic HBV or HCV was significantly higher than the estimated United Kingdom prevalence of 0.3% for each. We found no association between DILI and presence of serological markers of HBV or HCV. Three (5.3%) patients with serological markers of HBV or HCV infection had DILI compared to 25 (9.5%) patients without; P = 0.04. CONCLUSION: Viral hepatitis screening should be considered in TB patients. DILI risk was not increased in patients with HBV/HCV. PMID- 26269683 TI - Serum proinflammatory cytokines and nutritional status in pediatric chronic liver disease. AB - AIM: To evaluate the nutritional status and its association with proinflammatory cytokines in children with chronic liver disease. METHODS: We performed a cross sectional study with 43 children and adolescents, aged 0 to 17 years, diagnosed with chronic liver disease. All patients regularly attended the Pediatric Hepatology Unit and were under nutritional follow up. The exclusion criteria were fever from any etiology at the time of enrollment, inborn errors of the metabolism and any chronic illness. The severity of liver disease was assessed by Child-Pugh, Model for End-stage Liver Disease (MELD) and Pediatric End Stage Liver Disease (PELD) scores. Anthropometric parameters were height/age, body mass index/age and triceps skinfold/age according to World Health Organization standards. The cutoff points for nutritional status were risk of malnutrition (Z score < -1.00) and malnutrition (Z-score < -2.00). Interleukin-1beta (IL-1beta), IL-6 and tumor necrosis factor-alpha levels were assessed by commercial ELISA kits. For multivariate analysis, linear regression was applied to assess the association between cytokine levels, disease severity and nutritional status. RESULTS: The median (25(th)-75(th) centile) age of the study population was 60 (17-116)-mo-old, and 53.5% were female. Biliary atresia was the main cause of chronic liver disease (72%). With respect to Child-Pugh score, cirrhotic patients were distributed as follows: 57.1% Child-Pugh A, a mild presentation of the disease, 34.3% Child-Pugh B, a moderate stage of cirrhosis and 8.6% Child-Pugh C, were considered severe cases. PELD and MELD scores were only above the cutoff point in 5 cases. IL-6 values were increased in patients at nutritional risk (34.9%) compared with those who were well-nourished [7.12 (0.58-34.23) pg/mL vs 1.63 (0.53-3.43) pg/mL; P = 0.02], correlating inversely with triceps skinfold for-age z-score (rs = -0.61; P < 0.001). IL-6 levels were associated with liver disease severity assessed by Child-Pugh score (P = 0.001). This association remained significant after adjusting for nutritional status in a linear regression model. CONCLUSION: High IL-6 levels were found in children with chronic liver disease at nutritional risk. Inflammatory activity may be related to nutritional status deterioration in these patients. PMID- 26269684 TI - Interferon-lambda polymorphisms and response to pegylated interferon in Iranian hepatitis C patients. AB - AIM: To evaluate the efficacy of pegylated interferon in Iranian chronic hepatitis C patients in relation to interferon-lambda (IFNL) polymorphisms. METHODS: This study enrolled patients with chronic hepatitis C referred to the Tehran Blood Transfusion Hepatitis Clinic in 2011. Patients were included in the study if they had no concomitant hepatic illness, were negative for human immunodeficiency virus antibodies, and had no prior history of treatment with any type of pegylated interferon. Patients were treated with 180 MUg pegylated interferon alpha-2a (Pegaferon((r))) weekly and 800-1200 mg ribavirin daily for 24 or 48 wk depending on weight and hepatitis C virus (HCV) genotype. Blood samples were collected from patients to obtain DNA for determination of IFNL rs12979860 and rs8099917 polymorphisms. The virologic response in patients was then evaluated and compared between the different IFNL genotypes. RESULTS: A total of 152 patients with a mean age of 41.9 +/- 10.0 years were included in the study, of which 141/152 were men (92.8%). The most frequent HCV genotype was type 1, infecting 93/152 (61.2%) patients. Sustained virologic response (SVR) was achieved in 81.9% of patients with HCV genotype-1 and 91.1% of patients with HCV genotype-3. Treatment success was achieved in 91.2% (52/57) of patients with the IFNL rs12979860 CC genotype and 82.1% (78/95) in those with other genotypes. Similar treatment response rates were also observed in patients with rs8099917 TT (39/45; 86.7%) and non-TT (61/68; 89.7%) genotypes. Univariate analyses identified the following factors which influenced treatment response for inclusion in a multivariate analysis: age, HCV RNA level, stage of liver fibrosis, rs12979860 CC genotype, and aspartate transaminase level. A logistic regression analysis revealed that only the rs12979860 CC genotype was significantly associated with achievement of SVR (OR = 6.2; 95%CI: 1.2-31.9; P = 0.03). CONCLUSION: The rs12979860 CC genotype was associated with SVR in patients receiving pegylated interferon plus ribavirin, however, the SVR rate in other rs12979860 genotypes was also relatively high. PMID- 26269685 TI - Esophagojejunostomy after laparoscopic total gastrectomy by OrVilTM or hemi double stapling technique. AB - AIM: To investigate the feasibility, advantages and disadvantages of two types of anvil insertion techniques for esophagojejunostomy after laparoscopic total gastrectomy. METHODS: This was an open-label prospective cohort study. Laparoscopy-assisted radical total gastrectomy with D2 lymph node dissection was performed in 84 patients with primary non-metastatic gastric cancer confirmed by pre-operative histological examination. Overweight patients were excluded, as well as patients with peritoneal dissemination and invasion of adjacent organs. After total gastrectomy, all patients were randomized into two groups. Patients in Group I underwent esophagojejunostomy using a transorally-inserted anvil (OrVil(TM)), while patients in Group II underwent esophagojejunostomy using the hemi-double stapling technique (HDST). Both types of esophagojejunostomy were performed under laparoscopy. Patients' baseline characteristics, preoperative characteristics, perioperative characteristics, short-term postoperative outcomes and operation cost were compared between the two groups. The primary endpoint was evaluation of the surgical outcome (operating time, time of digestive tract reconstruction and time of anvil insertion) and the medical cost of each operation (operation cost and total cost of hospitalization). The secondary endpoints were time to solid diet, post-surgical hospitalization time, time to defecation, time to ambulation and intra-operative blood loss. In addition, complications were assessed and compared. RESULTS: Laparoscopic total gastrectomy and esophagojejunostomy were successfully performed in all 84 patients, without conversion to laparotomy. There were no significant differences in the operative time and time for total gastrectomy between the two groups (287.8 +/- 38.4 min vs 271.8 +/- 46.1 min, P = 0.09, and 147.7 +/- 31.6 min vs 159.8 +/- 33.8 min, P = 0.09, respectively). The time for digestive tract reconstruction and for anvil insertion were significantly decreased in Group II compared with Group I (47.8 +/ 12.1 min vs 55.4 +/- 15.7 min, P = 0.01, and 12.6 +/- 4.7 min vs 18.7 +/- 7.5 min, P = 0.001, respectively). Intra-operative blood loss (96.4 +/- 32.7 mL vs 88.2 +/- 36.9 mL, P = 0.28), time to defecation (3.5 +/- 0.9 d vs 3.2 +/- 1.1 d, P = 0.12), time to ambulation (3.9 +/- 0.7 d vs 3.6 +/- 1.1 d, P = 0.12), time to solid diet (7.6 +/- 1.4 d vs 8.0 +/- 2.7 d, P = 0.31) and total hospitalization (10.6 +/- 2.6 d vs 10.8 +/- 3.5 d, P = 0.80) were similar between the two groups. In addition, the total costs of hospitalization were similar between the two groups (73848.7 +/- 11781.0 RMB vs 70870.3 +/- 14003.5 RMB, P = 0.296), but operation cost was significantly higher in Group I compared with Group II (32401.9 +/- 1981.6 RMB vs 26961.9 +/- 2293.8 RMB, P < 0.001). CONCLUSION: Anvil insertion was faster and easier using the HDST technique compared with OrVil(TM), and was more cost-effective. There was no significant difference in safety. PMID- 26269686 TI - Effects of cereal fiber on bowel function: A systematic review of intervention trials. AB - AIM: To comprehensively review and quantitatively summarize results from intervention studies that examined the effects of intact cereal dietary fiber on parameters of bowel function. METHODS: A systematic literature search was conducted using PubMed and EMBASE. Supplementary literature searches included screening reference lists from relevant studies and reviews. Eligible outcomes were stool wet and dry weight, percentage water in stools, stool frequency and consistency, and total transit time. Weighted regression analyses generated mean change (+/- SD) in these measures per g/d of dietary fiber. RESULTS: Sixty-five intervention studies among generally healthy populations were identified. A quantitative examination of the effects of non-wheat sources of intact cereal dietary fibers was not possible due to an insufficient number of studies. Weighted regression analyses demonstrated that each extra g/d of wheat fiber increased total stool weight by 3.7 +/- 0.09 g/d (P < 0.0001; 95%CI: 3.50-3.84), dry stool weight by 0.75 +/- 0.03 g/d (P < 0.0001; 95%CI: 0.69-0.82), and stool frequency by 0.004 +/- 0.002 times/d (P = 0.0346; 95%CI: 0.0003-0.0078). Transit time decreased by 0.78 +/- 0.13 h per additional g/d (P < 0.0001; 95%CI: 0.53 1.04) of wheat fiber among those with an initial transit time greater than 48 h. CONCLUSION: Wheat dietary fiber, and predominately wheat bran dietary fiber, improves measures of bowel function. PMID- 26269687 TI - Allocation of patients with liver cirrhosis and organ failure to intensive care: Systematic review and a proposal for clinical practice. AB - AIM: To propose an allocation system of patients with liver cirrhosis to intensive care unit (ICU), and developed a decision tool for clinical practice. METHODS: A systematic review of the literature was performed in PubMed, MEDLINE and EMBASE databases. The search includes studies on hospitalized patients with cirrhosis and organ failure, or acute on chronic liver failure and/or intensive care therapy. RESULTS: The initial search identified 660 potentially relevant articles. Ultimately, five articles were selected; two cohort studies and three reviews were found eligible. The literature on this topic is scarce and no studies specifically address allocation of patients with liver cirrhosis to ICU. Throughout the literature, there is consensus that selection criteria for ICU admission should be developed and validated for this group of patients and multidisciplinary approach is mandatory. Based on current available data we developed an algorithm, to determine if a patient is candidate to intensive care if needed, based on three scoring systems: premorbid Child-Pugh Score, Model of End stage Liver Disease score and the liver specific Sequential Organ Failure Assessment score. CONCLUSION: There are no established systems for allocation of patients with liver cirrhosis to the ICU and no evidence-based recommendations can be made. PMID- 26269688 TI - Laparoscopic transhiatal approach for resection of an adenocarcinoma in long segment Barrett's esophagus. AB - Barrett's esophagus (BE) is a precursor of esophageal adenocarcinoma and is associated with gastroesophageal reflux disease, which is often preceded by a hiatal hernia. We describe a case of esophageal adenocarcinoma arising in long segment BE (LSBE) associated with a hiatal hernia that was successfully treated with a laparoscopic transhiatal approach (LTHA) without thoracotomy. The patient was a 42-year-old male who had previously undergone laryngectomy and tracheal separation to avoid repeated aspiration pneumonitis. An ulcerative lesion was found in a hiatal hernia by endoscopy and superficial esophageal cancer was also detected in the lower thoracic esophagus. The histopathological diagnosis of biopsy samples from both lesions was adenocarcinoma. There were difficulties with the thoracic approach because the patient had severe kyphosis and muscular contractures from cerebral palsy. Therefore, we performed subtotal esophagectomy by LTHA without thoracotomy. Using hand-assisted laparoscopic surgery, the esophageal hiatus was divided and carbon dioxide was introduced into the mediastinum. A hernial sac was identified on the cranial side of the right crus of the diaphragm and carefully separated from the surrounding tissues. Abruption of the thoracic esophagus was performed up to the level of the arch of the azygos vein via LTHA. A cervical incision was made in the left side of the permanent tracheal stoma, the cervical esophagus was divided, and gastric tube reconstruction was performed via a posterior mediastinal route. The operative time was 175 min, and there was 61 mL of intra-operative bleeding. A histopathological examination revealed superficial adenocarcinoma in LSBE. Our surgical procedure provided a good surgical view and can be safely applied to patients with a hiatal hernia and kyphosis. PMID- 26269689 TI - Wilson disease with hepatic presentation in an eight-month-old boy. AB - Wilson disease is an autosomal recessive disorder of copper metabolism that can cause fatal neurological and hepatic disease if not diagnosed and treated. The youngest child with normal liver function reported so far is an 8-mo-old Japanese boy with low ceruloplasmin levels, and the youngest child with elevated aminotransferase ever reported so far is a 9-mo-old Korean boy with confirmed by genetic testing. Here we report an 8-mo-old Chinese boy presented with elevated liver enzymes, and low serum ceruloplasmin level. Genetic analysis of ATP7B gene detected two heterozygous disease causing mutations (c.2621C>T/p.A874V and c.3809A>G/p.N1270S), and parental origins were determined. Persistent elevation of serum aminotransferase in this infant was normalized after zinc therapy. To our best knowledge, this is the youngest patient with elevated liver enzymes ever reported worldwide. We hope that this will raise awareness among pediatricians, leading to earlier diagnosis, timely treatment, and better clinical outcome. PMID- 26269690 TI - Admission-Group Salary Differentials in the United States: The Significance of Labor Market Institutional Selection of High-Skilled Workers. AB - In 1990 a temporary-to-permanent pathway was established for highly skilled workers admitted to the United States under nonimmigrant programs. The paper argues that this policy shift has allowed employers to play a crucial role in the immigration of highly skilled workers, thereby creating labor-market institutional selection that gives a salary advantage to highly skilled temporary admitted workers retained in the United States. Through analyses of the salary differentials among admission-category groups, the paper finds that the salary advantage is based on recruitment from Western countries, adjustment from temporary to permanent status after a second employer screening, working in the information technology sector and the private sector, holding a supervisory position, or having a skill-matched job, all of which are consequences of institutional selection rather than individual self-selection. Our results also reveal a difference between those admitted from abroad and those recruited from graduating foreign students in USA higher educational institutions, which suggests a distinction between overseas hiring and domestic hiring. Policy implications for the United States and other receiving countries are discussed. PMID- 26269693 TI - The Consolidated Framework for Implementation Research (CFIR): a useful theoretical framework for guiding and evaluating a guideline implementation process in a hospital-based nursing practice. AB - BACKGROUND: Implementing clinical practice guidelines (CPGs) in healthcare settings is a complex intervention involving both independent and interdependent components. Although the Consolidated Framework for Implementation Research (CFIR) has never been evaluated in a practical context, it appeared to be a suitable theoretical framework to guide an implementation process. The aim of this study was to evaluate the comprehensiveness, applicability and usefulness of the CFIR in the implementation of a fall-prevention CPG in nursing practice to improve patient care in an Austrian university teaching hospital setting. METHODS: The evaluation of the CFIR was based on (1) team-meeting minutes, (2) the main investigator's research diary, containing a record of a before-and after, mixed-methods study design embedded in a participatory action research (PAR) approach for guideline implementation, and (3) an analysis of qualitative and quantitative data collected from graduate and assistant nurses in two Austrian university teaching hospital departments. The CFIR was used to organise data per and across time point(s) and assess their influence on the implementation process, resulting in implementation and service outcomes. RESULTS: Overall, the CFIR could be demonstrated to be a comprehensive framework for the implementation of a guideline into a hospital-based nursing practice. However, the CFIR did not account for some crucial factors during the planning phase of an implementation process, such as consideration of stakeholder aims and wishes/needs when implementing an innovation, pre-established measures related to the intended innovation and pre-established strategies for implementing an innovation. For the CFIR constructs reflecting & evaluating and engaging, a more specific definition is recommended. The framework and its supplements could easily be used by researchers, and their scope was appropriate for the complexity of a prospective CPG-implementation project. The CFIR facilitated qualitative data analysis and provided a structure that allowed project results to be organised and viewed in a broader context to explain the main findings. CONCLUSIONS: The CFIR was a valuable and helpful framework for (1) the assessment of the baseline, process and final state of the implementation process and influential factors, (2) the content analysis of qualitative data collected throughout the implementation process, and (3) explaining the main findings. PMID- 26269696 TI - A VIEW OF TURKEY AND EUROPEAN RELATIONS FROM THE PERSPECTIVE OF MEDICAL LEGISLATION: AN ASSESMENT OF STATE OF PLAY. AB - The aim of this paper is to reflect the situation of health legislation alignment in Turkey in its accession process to the European Union and Customs Union Agreement, and to discuss the the EU's health priorities of in parallel with the Turkish ones. The health legislation alignment processes consist of three titles which are: European Union alignment process, the harmonization done in the framework of membership to Council of Europe, and the obligations under the Customs Union Agreement. Significant human resources are required for the adoption of the legislations which make ethically imperative the discussion of whether there is a harmony among the priorities of both parities. Unless this harmony and paralellisim is shown, the human resources appointed for the adoption of health legislation process would not prove their efficiency and effectiveness. In this article, the Customs Union and formal negotiations for full EU membership are included in the phrase "the alignment process to European Union". Council Decisions 1/95 and 2/97 ground on the obligations provided by the Customs Union Agreement. The reference document used to discuss the formal negotiation process for full membership to European Union is the Turkish National Program for the Adoption of the EU Acquis 2008-2013. The legislative obligations of Turkey arising from its membership of the Council of Europe, which has significant contributions to the medical legislation especially in the field of medical ethics, are also included in this article. PMID- 26269692 TI - CALDER: neutrinoless double-beta decay identification in TeO[Formula: see text] bolometers with kinetic inductance detectors. AB - Next-generation experiments searching for neutrinoless double-beta decay must be sensitive to a Majorana neutrino mass as low as 10[Formula: see text]. CUORE , an array of 988 TeO[Formula: see text] bolometers being commissioned at Laboratori Nazionali del Gran Sasso, features an expected sensitivity of 50-130[Formula: see text] at 90 % C.L. The background is expected to be dominated by [Formula: see text] radioactivity, and can be in principle removed by detecting the small amount of Cherenkov light emitted by the [Formula: see text] signal. The Cryogenic wide-Area Light Detectors with Excellent Resolution project aims at developing a small prototype experiment consisting of TeO[Formula: see text] bolometers coupled to high-sensitivity light detectors based on kinetic inductance detectors. The R&D is focused on the light detectors in view of the implementation in a next-generation neutrinoless double-beta decay experiment. PMID- 26269694 TI - Efficacy and safety of edoxaban versus enoxaparin for the prevention of venous thromboembolism following total hip arthroplasty: STARS J-V. AB - BACKGROUND: In the absence of thromboprophylaxis, patients undergoing total hip arthroplasty (THA) are at increased risk for venous thromboembolism (VTE). The objective of this study was to compare the efficacy and safety of edoxaban with enoxaparin for the prevention of VTE after THA in Japan. METHODS: This was a phase 3, double-blind, double-dummy, noninferiority study. Patients undergoing elective, unilateral primary THA were randomized to receive edoxaban 30 mg once daily (n = 307) or enoxaparin 2000 IU (equivalent to 20 mg) twice daily (n = 303) for 11 to 14 days. The primary efficacy endpoint was the incidence of VTE. Safety endpoints included the incidence of major or clinically relevant nonmajor (CRNM) bleeding. RESULTS: The incidence of VTE, based on venography and clinical surveillance, was 2.4 % in the edoxaban group and 6.9 % in the enoxaparin group (P <0.001). The absolute difference in the incidence of VTE was -4.5 % (95 % confidence interval [CI]: -8.6, -0.9), which was within the noninferiority margin set at 8 % for the difference and established the noninferiority of edoxaban to enoxaparin. Since the upper limit of the 95 % CI of the absolute difference was less than 0 %, the superiority of edoxaban over enoxaparin was demonstrated. The incidence of major or CRNM bleeding was 2.6 % in the edoxaban group and 3.7 % in the enoxaparin group (P = 0.475). CONCLUSIONS: Oral edoxaban 30 mg once daily was superior to subcutaneous enoxaparin 2000 IU twice daily in the prevention of VTE following THA without increasing the risk for major or CRNM bleeding. PMID- 26269695 TI - Origins of Effortful Control: Infant and Parent Contributions. AB - Effortful control (EC) refers to the ability to inhibit a dominant response to perform a subdominant one and has been shown as protective against a myriad of difficulties. Research examining precursors of EC has been limited to date, and in this study, infancy contributors to toddler EC were examined. Specifically, parent/family background variables (e.g., education, income), maternal temperament, perceived stress, and internalizing symptoms were addressed, along with infant temperament: positive affectivity/surgency (PAS), negative emotionality (NE), and regulatory capacity/orienting (RCO); and laboratory observation-based indicators of attention. Infant attention indexed by the latency to look away after initially orienting to the presented stimuli emerged as an important predictor of later EC, after accounting for other child and parent/family attributes, with shorter latencies predicting higher levels of EC. Mothers' extraversion and parenting stress were the only parent/family attributes to significantly contribute to the prediction of toddler EC, with the former promoting and the latter undermining the development of EC. Infant temperament factors were also examined as a moderator of parent/family influences, with results indicating a significant interaction between mothers' EC and infant RCO, so that children with greater RCO and mothers high in EC exhibited the highest EC scores in toddlerhood. PMID- 26269697 TI - Sustained Virological Response after 8-Week Treatment of Simeprevir with Peginterferon alpha-2a plus Ribavirin in a Japanese Female with Hepatitis C Virus Genotype 1b and IL28B Minor Genotype. AB - Direct-acting antivirals with or without peginterferon alpha (PEG-IFN alpha) plus ribavirin are now available for the treatment of hepatitis C virus (HCV) infection. Direct-acting antivirals are potent inhibitors of HCV replication, but some of them occasionally possess serious adverse events. We experienced a 64 year-old female with chronic HCV genotype 1b infection who showed elevated alanine aminotransferase of 528 IU/l at week 9 after the commencement of treatment of simeprevir with PEG-IFN alpha-2a plus ribavirin. However, she achieved sustained virological response at week 24 after the end of treatment. In Japan, we also have to treat elderly patients infected with HCV and/or advanced hepatic fibrosis. Until an effective interferon-free regimen is established, direct-acting antivirals with PEG-IFN plus ribavirin may still play a role in the treatment for certain patients. To avoid serious results from adverse events, careful attention and follow-up will be needed in the treatment course of simeprevir with PEG-IFN plus ribavirin for chronic HCV infection. PMID- 26269698 TI - Glycogenic Hepatopathy: Thinking Outside the Box. AB - Glycogenic hepatopathy (GH) remains underrecognized in adults as most clinicians mistake it for the more common hepatic abnormality associated with uncontrolled diabetes mellitus in this age group, non-alcoholic fatty liver disease. This is also complicated by the fact that both entities are indistinguishable on liver ultrasound. We herein describe a similar predicament in which a young adult female presented with bilateral upper quadrant abdominal pain, tender hepatomegaly, lactic acidosis and a >10-fold increase in liver enzymes, which worsened after the administration of high-dose steroids. Despite intravenous normal saline resuscitation, serum transaminitis persisted in a fluctuating manner. Ultimately, a liver biopsy confirmed GH. Biochemically, GH is driven by high amounts of both circulating glucose and insulin or by the administration of high-dose steroids. Improving glycemic control is the mainstay of treatment for GH. However, in our case, improvement in glycated hemoglobin of just 0.6% was enough to achieve symptomatic relief, supporting recent claims of the involvement of other identified factors in disease development. PMID- 26269699 TI - Bezoar in a Pediatric Oncology Patient Treated with Coca-Cola. AB - A bezoar is a mass of indigestible material. Bezoars can present with a gradual onset of non-specific gastrointestinal symptoms including abdominal pain, nausea and vomiting. However, bezoars can result in more serious conditions such as intestinal bleeding or obstruction. Without quick recognition, particularly in susceptible individuals, the diagnosis and treatment can be delayed. Currently resolution is achieved with enzymatic dissolution, endoscopic fragmentation or surgery. We describe, to our knowledge, the first pediatric patient with lymphoma to have had a bezoar treated with Coca-Cola. PMID- 26269700 TI - Pancreatic and Gastric Heterotopia with Associated Submucosal Lipoma Presenting as a 7-cm Obstructive Tumor of the Ileum: Resection with Double Balloon Enteroscopy. AB - Pancreatic and gastric heterotopias are rare clinical entities which have been identified throughout the entire length of the gastrointestinal tract. Combined gastric and pancreatic heterotopias, although unusual, have been described in the duodenum and jejunum, and in other structures, including Meckel's diverticulum and the ampulla of Vater. We report a novel case of pancreatic and gastric heterotopia with an associated submucosal lipoma in a 38-year-old female with a recent history of rectal cancer and chronic crampy abdominal pain. On computed tomography, a 7-cm luminal polypoid mass extending into the distal ileum was discovered. The mass was successfully resected using retrograde double balloon enteroscopy. We believe this is the first report of all three histological entities co-existing in an obstructive ileal lesion in an adult. It highlights endoscopic resection trough double enteroscopy as a safe alternative to more invasive surgical approaches for this type of lesion. PMID- 26269701 TI - Abrupt Intralesional Color Change on Dermoscopy as a New Indicator of Early Superficial Spreading Melanoma in a Japanese Woman. AB - Diagnosis of superficial spreading melanoma in the early stage is often difficult, even with dermoscopy. We report the case of a 37-year-old Japanese woman with superficial spreading melanoma in her left buttock. The lesion developed 20 years before becoming visible and gradually enlarged over the past few years without any symptoms. Physical examination showed a well-demarcated dark-brown macule 10 mm in diameter. Dermoscopy demonstrated a central dark area with a blue-grey structureless area, a milky-red area with irregular blue-grey dots or globules suggestive of regression structures, and multifocal black pigmentation with whitish scaly areas. An abrupt intralesional change in color from a central dark area to a peripheral light-brown area was also seen. The peripheral area showed an atypical pigment network with an obscure mesh and holes. Histopathologic examination of the lesion showed acanthosis with melanocytic proliferation and nuclear atypia, a band-like lymphocytic infiltrate, melanophages and a few nests of melanocytes just beneath the epidermis. The epidermal melanocytes were positive for S-100, Melan-A and HMB-45, but the dermal nests of melanocytes were negative for HMB-45 and positive for S-100 and Melan-A. A diagnosis of superficial spreading melanoma with a tumor thickness of 0.4 mm (pT1aN0M0, stage 1A) was established based on the clinical, dermoscopic and histopathologic findings. This case suggests that dermoscopy is useful in the diagnosis of this condition. An abrupt intralesional change of color might be a new indicator of early superficial spreading melanoma. PMID- 26269702 TI - Porphyria Cutanea Tarda Masquerading as Epidermolysis Bullosa Acquisita: A Report of Two Cases. AB - Porphyria cutanea tarda (PCT) is the most common type of porphyria worldwide and is often initially diagnosed when cutaneous manifestations arise. We present two patients where misdiagnosis of PCT occurred due to the condition masquerading as epidermolysis bullosa acquisita histologically. In patients with undifferentiated bullous/erosive skin conditions occurring in photo-distributed regions, PCT should be considered in the differential diagnosis irrespective of histopathological findings on biopsies and further investigated and treated appropriately. PMID- 26269703 TI - Primary Cutaneous Chrysosporium Infection following Ear Piercing: A Case Report. AB - Chrysosporium is a large genus of saprophytic fungi that is commonly found in the soil. Infection caused by this organism is rare in humans and typically occurs in immunocompromised patients. Primary cutaneous Chrysosporium infection is relatively rare and has been reported in a heart transplant patient. The prognosis is usually favorable, but very poor in the setting of persistent profound immunosuppression. We herein report a case of primary cutaneous Chrysosporium infection following ear piercing in an immunocompetent patient. It is important for clinicians to consider this condition in patients with slow onset skin and soft tissue infection following cutaneous injury, even in an immunocompetent setting. PMID- 26269704 TI - The role of stripe orientation in target capture success. AB - INTRODUCTION: 'Motion dazzle' refers to the hypothesis that high contrast patterns such as stripes and zigzags may have evolved in a wide range of animals as they make it difficult to judge the trajectory of an animal in motion. Despite recent research into this idea, it is still unclear to what extent stripes interfere with motion judgement and if effects are seen, what visual processes might underlie them. We use human participants performing a touch screen task in which they attempt to 'catch' moving targets in order to determine whether stripe orientation affects capture success, as previous research has suggested that different stripe orientations may be processed differently by the visual system. We also ask whether increasing the number of targets presented in a trial can affect capture success, as previous research has suggested that motion dazzle effects may be larger in groups. RESULTS: When single targets were presented sequentially within each trial, we find that perpendicular and oblique striped targets are captured at a similar rate to uniform grey targets, but parallel striped targets are significantly easier to capture. However, when multiple targets are present simultaneously during a trial we find that striped targets are captured in fewer attempts and more quickly than grey targets. CONCLUSIONS: Our results suggest that there may be differences in capture success based on target pattern orientation, perhaps suggesting that different visual mechanisms are involved in processing of parallel stripes compared to perpendicular/oblique stripes. However, these results do not seem to generalise to trials with multiple targets, and contrary to previous predictions, striped targets appear to be easier to capture when multiple targets are present compared to being presented individually. These results suggest that the different orientations of stripes seen on animals in nature (such as in fish and snakes) may serve different purposes, and that it is unclear whether motion dazzle effects may have greater benefits for animals living in groups. PMID- 26269705 TI - Retraction Note: Alcohol consumption and hormonal alterations related to muscle hypertrophy: a review. AB - [This retracts the article DOI: 10.1186/1743-7075-11-26.]. PMID- 26269706 TI - Diesel engine exhaust and lung cancer risks - evaluation of the meta-analysis by Vermeulen et al. 2014. AB - BACKGROUND: Vermeulen et al. 2014 published a meta-regression analysis of three relevant epidemiological US studies (Steenland et al. 1998, Garshick et al. 2012, Silverman et al. 2012) that estimated the association between occupational diesel engine exhaust (DEE) exposure and lung cancer mortality. The DEE exposure was measured as cumulative exposure to estimated respirable elemental carbon in MUg/m(3)-years. Vermeulen et al. 2014 found a statistically significant dose response association and described elevated lung cancer risks even at very low exposures. METHODS: We performed an extended re-analysis using different modelling approaches (fixed and random effects regression analyses, Greenland/Longnecker method) and explored the impact of varying input data (modified coefficients of Garshick et al. 2012, results from Crump et al. 2015 replacing Silverman et al. 2012, modified analysis of Moehner et al. 2013). RESULTS: We reproduced the individual and main meta-analytical results of Vermeulen et al. 2014. However, our analysis demonstrated a heterogeneity of the baseline relative risk levels between the three studies. This heterogeneity was reduced after the coefficients of Garshick et al. 2012 were modified while the dose coefficient dropped by an order of magnitude for this study and was far from being significant (P = 0.6). A (non-significant) threshold estimate for the cumulative DEE exposure was found at 150 MUg/m(3)-years when extending the meta analyses of the three studies by hockey-stick regression modelling (including the modified coefficients for Garshick et al. 2012). The data used by Vermeulen and colleagues led to the highest relative risk estimate across all sensitivity analyses performed. The lowest relative risk estimate was found after exclusion of the explorative study by Steenland et al. 1998 in a meta-regression analysis of Garshick et al. 2012 (modified), Silverman et al. 2012 (modified according to Crump et al. 2015) and Mohner et al. 2013. The meta-coefficient was estimated to be about 10-20 % of the main effect estimate in Vermeulen et al. 2014 in this analysis. CONCLUSIONS: The findings of Vermeulen et al. 2014 should not be used without reservations in any risk assessments. This is particularly true for the low end of the exposure scale. PMID- 26269707 TI - Sickness absenteeism and associated factors among horticulture employees in lume district, southeast Ethiopia. AB - BACKGROUND: Sickness absenteeism is the major occupational health problem in developing countries where the majority of working population are engaged in hazardous sectors, such as agriculture. However, there is a dearth of studies clarifying the situation in most of Subsaharan African countries, like Ethiopia. The present study determined the magnitude of sickness absenteeism and associated factors among horticulture employees in Lume District, southeast Ethiopia. METHODS: An institutional-based cross-sectional study was conducted among horticulture employees in Lume District, southeast Ethiopia from March to May 2014. Stratified sampling followed by simple random sampling techniques was used to select the study participants. A pre-tested and structured questionnaire was used to collect data. Multivariable analyses were employed to see the effect of explanatory variables on dependent variable. RESULTS: The magnitude of sickness absenteeism was 58.8 % [95 % CI: (54.9, 62.5)] in the past three months. Absence of periodic medical checkup, working for more than 48 h per week, working overtime, job dissatisfaction, and job stress were factors significantly associated with sickness absenteeism. CONCLUSIONS: In this study a relatively higher rate of sickness absenteeism was reported compared to other studies. Interventions to reduce sickness absenteeism should focus on areas, such as periodic medical checkup, monitoring work schedules, improving employees' job satisfaction, and managing job stress. PMID- 26269708 TI - Factors associated with exclusive breastfeeding practices in Debre Berhan District, Central Ethiopia: a cross sectional community based study. AB - BACKGROUND: Globally, an estimated 6.3 million children under-five years of age died in the year 2013. To reduce the burden of morbidity and mortality of infants, Ethiopia adopted the World Health Organization (WHO) recommendation of exclusive breastfeeding (EBF) for the first six months of life. The objective of this study was to assess factors associated with EBF practices among mothers who have an infant aged below 12 months in Debre Berhan District, Ethiopia. METHODS: In this study we employed a cross sectional community based quantitative survey method, and data were collected from January through April 2014. Univariate statistical analysis was used to describe variables using frequencies and percentages. Multivariable logistic regression model was developed; the factors associated with EBF practice were identified. RESULT: We enrolled 634 mothers with their index infant aged under 12 months. Four hundred thirty five (68.6 %; 95 % CI: 64.9 %, 72.2 %) mothers practiced EBF to six months. In this study 83.4 % of mothers were knowledgeable with the recommended duration of EBF. About 97.5 % of mothers had a positive attitude towards EBF practice. Mothers from rural places were 4.54 times likely to EBF than mothers residing in urban areas Adjusted Odds Ratio (AOR 4.54; 95 % CI: 2.64, 7.81, p = 0.001). The odds of mothers aged 25 to 35 years to practice EBF was up to 8.9 times more than mothers aged less than 25 years (AOR 8.99; 95 % CI: 4.56, 17.73, p = 0.001). The odds of mothers who didn't receive infant feeding counselling was 0.42 times less likely to practice EBF than those who received Counselling services (AOR 0.42; 95 % CI: 0.24, 0.73, p = 0.002). Employed mothers were found to be 0.36 times less likely to practice EBF than housewives (AOR 0.36; 95 % CI: 0.18, 0.73, p = 0.005). Household income did not show a statistically significant association with EBF. CONCLUSIONS: The knowledge and attitude of mothers towards EBF was found to be very high. In this study, two thirds of mothers practiced exclusive breastfeeding. Improving access to information on recommended infant feeding during routine maternal and child health services is recommended. It is important to encourage EBF among the young, employed and urban mothers through proper counselling and mother friendly work environment. PMID- 26269710 TI - Toward the Rational Benchmarking of Homogeneous H2-Evolving Catalysts. AB - Molecular electrocatalysts for H2 evolution are usually studied under various conditions (solvent, proton sources) that prevent direct comparison of their performances. We provide here a rational method for such a benchmark based on (i) the recent analysis of the current-potential response for two-electron-two-step mechanisms and (ii) the derivation of catalytic Tafel plots reflecting the interdependency of turnover frequency and overpotential based on the intrinsic properties of the catalyst, independently of contingent factors such as the cell characteristics. Such a methodology is exemplified on a series of molecular catalysts among the most efficient in recent literature. PMID- 26269709 TI - The role of the open abdomen procedure in managing severe abdominal sepsis: WSES position paper. AB - The open abdomen (OA) procedure is a significant surgical advance, as part of damage control techniques in severe abdominal trauma. Its application can be adapted to the advantage of patients with severe abdominal sepsis, however its precise role in these patients is still not clear. In severe abdominal sepsis the OA may allow early identification and draining of any residual infection, control any persistent source of infection, and remove more effectively infected or cytokine-loaded peritoneal fluid, preventing abdominal compartment syndrome and deferring definitive intervention and anastomosis until the patient is appropriately resuscitated and hemodynamically stable and thus better able to heal. However, the OA may require multiple returns to the operating room and may be associated with significant complications, including enteroatmospheric fistulas, loss of abdominal wall domain and large hernias. Surgeons should be aware of the pathophysiology of severe intra-abdominal sepsis and always keep in mind the option of using open abdomen to be able to use it in the right patient at the right time. PMID- 26269711 TI - Complex and extensive post-transcriptional regulation revealed by integrative proteomic and transcriptomic analysis of metabolite stress response in Clostridium acetobutylicum. AB - BACKGROUND: Clostridium acetobutylicum is a model organism for both clostridial biology and solvent production. The organism is exposed to its own toxic metabolites butyrate and butanol, which trigger an adaptive stress response. Integrative analysis of proteomic and RNAseq data may provide novel insights into post-transcriptional regulation. RESULTS: The identified iTRAQ-based quantitative stress proteome is made up of 616 proteins with a 15 % genome coverage. The differentially expressed proteome correlated poorly with the corresponding differential RNAseq transcriptome. Up to 31 % of the differentially expressed proteins under stress displayed patterns opposite to those of the transcriptome, thus suggesting significant post-transcriptional regulation. The differential proteome of the translation machinery suggests that cells employ a different subset of ribosomal proteins under stress. Several highly upregulated proteins but with low mRNA levels possessed mRNAs with long 5'UTRs and strong RBS scores, thus supporting the argument that regulatory elements on the long 5'UTRs control their translation. For example, the oxidative stress response rubrerythrin was upregulated only at the protein level up to 40-fold without significant mRNA changes. We also identified many leaderless transcripts, several displaying different transcriptional start sites, thus suggesting mRNA-trimming mechanisms under stress. Downregulation of Rho and partner proteins pointed to changes in transcriptional elongation and termination under stress. CONCLUSIONS: The integrative proteomic-transcriptomic analysis demonstrated complex expression patterns of a large fraction of the proteome. Such patterns could not have been detected with one or the other omic analyses. Our analysis proposes the involvement of specific molecular mechanisms of post-transcriptional regulation to explain the observed complex stress response. PMID- 26269712 TI - Expression of the Acidothermus cellulolyticus E1 endoglucanase in Caldicellulosiruptor bescii enhances its ability to deconstruct crystalline cellulose. AB - BACKGROUND: The Caldicellulosiruptor bescii genome encodes a potent set of carbohydrate-active enzymes (CAZymes), found primarily as multi-domain enzymes that exhibit high cellulolytic and hemicellulolytic activity on and allow utilization of a broad range of substrates, including plant biomass without conventional pretreatment. CelA, the most abundant cellulase in the C. bescii secretome, uniquely combines a GH9 endoglucanase and a GH48 exoglucanase in one protein. The most effective commercial enzyme cocktails used in vitro to pretreat biomass are derived from fungal cellulases (cellobiohydrolases, endoglucanases and a beta-d-glucosidases) that act synergistically to release sugars for microbial conversion. The C. bescii genome contains six GH5 domains in five different open reading frames. Four exist in multi-domain proteins and two as single catalytic domains. E1 is a GH5 endoglucanase reported to have high specific activity and simple architecture and is active at the growth temperature of C. bescii. E1 is an endo-1,4-beta-glucanase linked to a family 2 carbohydrate binding module shown to bind primarily to cellulosic substrates. We tested if the addition of this protein to the C. bescii secretome would improve its cellulolytic activity. RESULTS: In vitro analysis of E1 and CelA shows synergistic interaction. The E1 gene from Acidothermus cellulolyticus was cloned and expressed in C. bescii under the transcriptional control of the C. bescii S layer promoter, and secretion was directed by the addition of the C. bescii CelA signal peptide sequence. The vector was integrated into the C. bescii chromosome at a site previously showing no detectable detrimental consequence. Increased activity of the secretome of the strain containing E1 was observed on both carboxymethylcellulose (CMC) and Avicel. Activity against CMC increased on average 10.8 % at 65 degrees C and 12.6 % at 75 degrees C. Activity against Avicel increased on average 17.5 % at 65 degrees C and 16.4 % at 75 degrees C. CONCLUSIONS: Expression and secretion of E1 in C. bescii enhanced the cellulolytic ability of its secretome. These data agree with in vitro evidence that E1 acts synergistically with CelA to digest cellulose and offer the possibility of engineering additional enzymes for improved biomass deconstruction with the knowledge that C. bescii can express a gene from Acidothermus, and perhaps other heterologous genes, effectively. PMID- 26269713 TI - Combining free and aggregated cellulolytic systems in the cellulosome-producing bacterium Ruminiclostridium cellulolyticum. AB - BACKGROUND: Ruminiclostridium cellulolyticum and Lachnoclostridium phytofermentans (formerly known as Clostridium cellulolyticum and Clostridium phytofermentans, respectively) are anaerobic bacteria that developed different strategies to depolymerize the cellulose and the related plant cell wall polysaccharides. Thus, R. cellulolyticum produces large extracellular multi enzyme complexes termed cellulosomes, while L. phytofermentans secretes in the environment some cellulose-degrading enzymes as free enzymes. In the present study, the major cellulase from L. phytofermentans was introduced as a free enzyme or as a cellulosomal component in R. cellulolyticum to improve its cellulolytic capacities. RESULTS: The gene at locus Cphy_3367 encoding the major cellulase Cel9A from L. phytofermentans and an engineered gene coding for a modified enzyme harboring a R. cellulolyticum C-terminal dockerin were cloned in an expression vector. After electrotransformation of R. cellulolyticum, both forms of Cel9A were found to be secreted by the corresponding recombinant strains. On minimal medium containing microcrystalline cellulose as the sole source of carbon, the strain secreting the free Cel9A started to grow sooner and consumed cellulose faster than the strain producing the cellulosomal form of Cel9A, or the control strain carrying an empty expression vector. All strains reached the same final cell density but the strain producing the cellulosomal form of Cel9A was unable to completely consume the available cellulose even after an extended cultivation time, conversely to the two other strains. Analyses of their cellulosomes showed that the engineered form of Cel9A bearing a dockerin was successfully incorporated in the complexes, but its integration induced an important release of regular cellulosomal components such as the major cellulase Cel48F, which severely impaired the activity of the complexes on cellulose. In contrast, the cellulosomes synthesized by the control and the free Cel9A secreting strains displayed similar composition and activity. Finally, the most cellulolytic strain secreting free Cel9A, was also characterized by an early production of lactate, acetate and ethanol as compared to the control strain. CONCLUSIONS: Our study shows that the cellulolytic capacity of R. cellulolyticum can be augmented by supplementing the cellulosomes with a free cellulase originating from L. phytofermentans, whereas integration of the heterologous enzyme in the cellulosomes is rather unfavorable. PMID- 26269714 TI - Aneusomy detection with Karyolite-Bac on Beads(r) is a cost-efficient and high throughput strategy in the molecular analyses of the early pregnancy conception losses. AB - BACKGROUND: Approximately 10-15 % of all clinically recognized pregnancies end in miscarriage, the majority of them occur during the first trimester, underlying the cause of the loss. Genetic analysis of fetal tissues has the potential to provide valuable information and is highly recommended in some cases. Around 3-4 years ago, the gold standard for the analysis was the GTG Kayrotype, is well known that around 50 % of the tissue samples received failed to grow in culture. Different molecular techniques are used to improve the quality and the specificity of the study, intending to circumvent the limits of the Karyotype. RESULTS: Karyolite-BoBsTM (KL-BoBTM) assay is a recent bead-based suspension, low density array technology with consistent results, probed that is an efficient molecular method to detect aneusomies in early pregnancy losses. Fifty samples from abortions were analyzed in order to probe and give more information about the methodology and analyze if KL-BoBsTM is a good and cost-efficient strategy. We detected 32 % of chromosomal abnormalities, in some of the cases more than one aberration was identified, the array CGH validate the observations. CONCLUSIONS: This molecular strategy is a cost-effective sensitive tool in the early pregnancy loss study. PMID- 26269715 TI - An interstitial deletion at 8q23.1-q24.12 associated with Langer-Giedion syndrome/ Trichorhinophalangeal syndrome (TRPS) type II and Cornelia de Lange syndrome 4. AB - BACKGROUND: There are three distinct subtypes of Trichorhinophalangeal syndrome (TRPS); TRPS type I, TRPS type II and TRPS type III. Features common to all three subtypes include sparse, slowly growing scalp hair, laterally sparse eyebrows, a bulbous tip of the nose (pear-shaped), and protruding ears. Langer-Giedion syndrome (LGS) or TRPS type II is a contiguous gene syndrome on 8q24.1, involving loss of functional copies of the TRPS1 and EXT1 genes. We report a male patient that was referred to the Department of Medical Genetics due to hypotonia and dysmorphic facial features. RESULTS: Cytogenetic and array- Comparative Genomic Hybridization (aCGH) analysis revealed that the patient was a carrier of an interstitial deletion at 8q23.1-q24.12 of 12,5 Mb. Parental karyotype indicated that the father carried an apparently balanced insertion: 46, ChiUpsilon, der(10)ins(10;8)(q22;q23q24). CONCLUSIONS: This is the first report of an apparently balanced insertion including chromosomes 8 and 10 contributing to the etiology of LGS/ TRPS type II. Tauimely diagnosis of parental balanced chromosomal rearrangements can reduce the risk of subsequent miscarriages as well as abnormal offspring. PMID- 26269716 TI - Informative gene network for chemotherapy-induced peripheral neuropathy. AB - BACKGROUND: Host genetic variability has been implicated in chemotherapy-induced peripheral neuropathy (CIPN). A dose-limiting toxicity for chemotherapy agents, CIPN is also a debilitating condition that may progress to chronic neuropathic pain. We utilized a bioinformatics approach, which captures the complexity of intracellular and intercellular interactions, to identify genes for CIPN. METHODS: Using genes pooled from the literature as a starting point, we used Ingenuity Pathway Analysis (IPA) to generate gene networks for CIPN. RESULTS: We performed IPA core analysis for genes associated with platinum-, taxane- and platinum-taxane-induced neuropathy. We found that IL6, TNF, CXCL8, IL1B and ERK1/2 were the top genes in terms of the number of connections in platinum induced neuropathy and TP53, MYC, PARP1, P38 MAPK and TNF for combined taxane platinum-induced neuropathy. CONCLUSION: Neurotoxicity is common in cancer patients treated with platinum compounds and anti-microtubule agents and CIPN is one of the debilitating sequela. The bioinformatic approach helped identify genes associated with CIPN in cancer patients. PMID- 26269717 TI - ENVE: a novel computational framework characterizes copy-number mutational landscapes in colorectal cancers from African American patients. AB - Reliable detection of somatic copy-number alterations (sCNAs) in tumors using whole-exome sequencing (WES) remains challenging owing to technical (inherent noise) and sample-associated variability in WES data. We present a novel computational framework, ENVE, which models inherent noise in any WES dataset, enabling robust detection of sCNAs across WES platforms. ENVE achieved high concordance with orthogonal sCNA assessments across two colorectal cancer (CRC) WES datasets, and consistently outperformed a best-in-class algorithm, Control FREEC. We subsequently used ENVE to characterize global sCNA landscapes in African American CRCs, identifying genomic aberrations potentially associated with CRC pathogenesis in this population. ENVE is downloadable at https://github.com/ENVE-Tools/ENVE. PMID- 26269718 TI - Achieving high-sensitivity for clinical applications using augmented exome sequencing. AB - BACKGROUND: Whole exome sequencing is increasingly used for the clinical evaluation of genetic disease, yet the variation of coverage and sensitivity over medically relevant parts of the genome remains poorly understood. Several sequencing-based assays continue to provide coverage that is inadequate for clinical assessment. METHODS: Using sequence data obtained from the NA12878 reference sample and pre-defined lists of medically-relevant protein-coding and noncoding sequences, we compared the breadth and depth of coverage obtained among four commercial exome capture platforms and whole genome sequencing. In addition, we evaluated the performance of an augmented exome strategy, ACE, that extends coverage in medically relevant regions and enhances coverage in areas that are challenging to sequence. Leveraging reference call-sets, we also examined the effects of improved coverage on variant detection sensitivity. RESULTS: We observed coverage shortfalls with each of the conventional exome-capture and whole-genome platforms across several medically interpretable genes. These gaps included areas of the genome required for reporting recently established secondary findings (ACMG) and known disease-associated loci. The augmented exome strategy recovered many of these gaps, resulting in improved coverage in these areas. At clinically-relevant coverage levels (100 % bases covered at >=20*), ACE improved coverage among genes in the medically interpretable genome (>90 % covered relative to 10-78 % with other platforms), the set of ACMG secondary finding genes (91 % covered relative to 4-75 % with other platforms) and a subset of variants known to be associated with human disease (99 % covered relative to 52-95 % with other platforms). Improved coverage translated into improvements in sensitivity, with ACE variant detection sensitivities (>97.5 % SNVs, >92.5 % InDels) exceeding that observed with conventional whole-exome and whole-genome platforms. CONCLUSIONS: Clinicians should consider analytical performance when making clinical assessments, given that even a few missed variants can lead to reporting false negative results. An augmented exome strategy provides a level of coverage not achievable with other platforms, thus addressing concerns regarding the lack of sensitivity in clinically important regions. In clinical applications where comprehensive coverage of medically interpretable areas of the genome requires higher localized sequencing depth, an augmented exome approach offers both cost and performance advantages over other sequencing-based tests. PMID- 26269719 TI - Explaining, not just predicting, drives interest in personal genomics. AB - BACKGROUND: There is a widespread assumption that risk prediction is the major driver of customer interest in personal genomic testing (PGT). However, some customers may also be motivated by finding out whether their existing diseases have a genetic etiology. We evaluated the impact of an existing medical diagnosis on customer interest in condition-specific results from PGT. METHODS: Using a prospective online survey of PGT customers, we measured customer interest prior to receiving PGT results for 11 health conditions, and examined the association between interest and personal medical history of these conditions using logistic regression. RESULTS: We analyzed data from 1,538 PGT customers, mean age 48.7 years, 61 % women, 90 % White, and 47 % college educated. The proportion of customers who were 'very interested' in condition-specific PGT varied considerably, from 28 % for ulcerative colitis to 68% for heart disease. After adjusting for demographic and personal characteristics including family history, having a diagnosis of the condition itself was significantly associated with interest in genetic testing for risk of that condition, with odds ratios ranging from 2.07 (95 % CI 1.28-3.37) for diabetes to 19.99 (95 % CI 4.57-87.35) for multiple sclerosis. CONCLUSIONS: PGT customers are particularly interested in genetic markers for their existing medical conditions, suggesting that the value of genetic testing is not only predictive, but also explanatory. PMID- 26269720 TI - Characterising the biophysical properties of normal and hyperkeratotic foot skin. AB - BACKGROUND: Plantar foot skin exhibits unique biophysical properties that are distinct from skin on other areas of the body. This paper characterises, using non-invasive methods, the biophysical properties of foot skin in healthy and pathological states including xerosis, heel fissures, calluses and corns. METHODS: Ninety three people participated. Skin hydration, elasticity, collagen and elastin fibre organisation and surface texture was measured from plantar calluses, corns, fissured heel skin and xerotic heel skin. Previously published criteria were applied to classify the severity of each skin lesion and differences in the biophysical properties compared between each classification. RESULTS: Calluses, corns, xerotic heel skin and heel fissures had significantly lower levels of hydration; less elasticity and greater surface texture than unaffected skin sites (p < 0.01). Some evidence was found for a positive correlation between hydration and elasticity data (r <= 0.65) at hyperkeratotic sites. Significant differences in skin properties (with the exception of texture) were noted between different classifications of skin lesion. CONCLUSIONS: This study provides benchmark data for healthy and different severities of pathological foot skin. These data have applications ranging from monitoring the quality of foot skin, to measuring the efficacy of therapeutic interventions. PMID- 26269721 TI - Use of hand-held Doppler ultrasound examination by podiatrists: a reliability study. AB - BACKGROUND: Hand held Doppler examination is a frequently used non-invasive vascular assessment utilised by podiatrists. Despite this, the reliability of hand-held Doppler has not been thoroughly investigated. Given the importance of Doppler in completing a vascular assessment of the lower limb, it is essential to determine the reliability of the interpretation of this testing method in practicing podiatrists. METHODS: This was a multi-centre inter and intra-rater reliability study. Four podiatrists (the raters) participated in this study, two public and two private practitioners. Three aspects of Doppler use were examined; (i) use of Doppler (i.e., technique and interpretation), (ii) interpretation of Doppler audio sounds, and (iii) interpretation of visual Doppler waveforms (i.e., tracings). Participants meeting current guidelines for vascular screening attended two testing sessions, 1 week apart at either the private practice (n = 32), or the public practice (n = 31). To assess use of Doppler, the raters evaluated the Doppler waveforms that they collected, rating them as mono-phasic or multi-phasic. To assess Doppler audio sounds and visual Doppler waveforms, raters were required to evaluate 30 audio recordings of Doppler sounds and 30 waveform tracings, respectively, that were previously recorded and chosen at random by the researchers. Cohen's kappa (kappa) statistics were used to calculate inter and intra-rater reliability using SPSS version 19. RESULTS: Use of Doppler demonstrated the lowest reliability for both pairs of clinicians (inter-rater reliability kappa 0.20 to 0.24 and intra-rater reliability kappa 0.27 to 0.42). The public podiatrists showed higher reliability in audio interpretation (inter-tester reliability kappa 0.61, intra-tester reliability kappa 1.00) compared to the private podiatrists (inter-tester reliability kappa 0.31, intra-tester reliability kappa 0.53). Evaluation of Doppler waveform tracings demonstrated highest reliability, with inter-rater reliability ranging from kappa 0.77 to 0.90 and intra-rater reliability from kappa 0.81 to 1.00. CONCLUSIONS: There is a need for ongoing education for podiatrists using Doppler in clinical practice, as the reliability for the clinical use of the Doppler was low. This indicates that technique could be an issue. There is also a need to further evaluate if hand-held Doppler equipment, using the examinations that we evaluated, is suitable for use in the contexts examined in this study. PMID- 26269722 TI - Effects of caloric restriction and low glycemic index diets associated with metformin on glucose metabolism and cortisol response in overweight/obese subjects: a case series study. AB - BACKGROUND: To determine whether cortisol secretion and glucocorticoid receptors in lymphocytes and monocytes are altered in patients with impaired glucose tolerance, and whether treatment with a hypocaloric diet and metformin could interfere with these aspects. METHODS: This is an analytical, interventional, case series study. Patients with impaired glucose tolerance were included. They received 500 mg of metformin twice daily and followed a low glycemic index diet for 16 weeks. Cortisol levels were assessed at 8:00 A.M. before and after use of 0.25 mg of dexamethasone at 11:00 P.M. the day before. RESULTS: Sixteen subjects (9 men) were included. Normal basal levels of cortisol and adequate responses to the low dose of dexamethasone were observed before and after treatment. There was no significant correlation between the parameters evaluated and cortisol levels. Nevertheless, there was a strong correlation between the number of glucocorticoid receptors, BMI (r = 0.88; p = 0.02), and insulin AUC (r = 0.94; p = 0.005) before treatment; after treatment, all these associations ceased to exist. CONCLUSION: The cortisol secretion remained normal in the group of patients with impaired glucose tolerance. Treatment with metformin and diet did not change this condition. However, glucocorticoid receptor number had a strong correlation with insulin, due to insulin resistance, but this characteristic was lost after treatment. PMID- 26269723 TI - Identification of tumour-related proteins as potential screening markers by proteome analysis-protein profiles of human saliva as a predictive and prognostic tool. AB - The analysis of biomarkers in saliva as a clinical application offers an attractive, simple and rapid diagnostic tool for the short- and long-term monitoring of pathological disorders and drug therapy. The collection of saliva, either in the pure or in its fractionated form, is a relatively easy and non invasive procedure that is not harmful to the patients and has no complications at all. However, the fluid collection must be clearly defined due to variations in saliva composition, flow rate and day-to-day variability. In order to minimise possible variations, saliva from five patients without squamous cell carcinoma (SCC) pathology and five with suspicion of oral squamous carcinoma (OSCC) were collected and matched at different days and analysed by two-dimensional polyacrylamide gel electrophoresis (2DE-PAGE). Approximately 800 spots were identified, corresponding to 151 different gene products. The list of identified proteins includes a large number of structural proteins like keratins, keratin subunits, enzymes and enzyme inhibitors, cytokines, immunoglobulins as well as amylase and other salivary specific glycoproteins. The majority of proteins that are localised in oral epithelia cells were found as unsolved debris in saliva. One of the identified proteins was significantly overexpressed in OSCC and was selected for further validation by Western blot analysis. PMID- 26269724 TI - Analysis of Mandibular Test Specimens Used to Assess a Bone Fixation System. AB - The aim of this study was to assess through biomechanical testing if different synthetic materials used to fabricate test specimens have a different biomechanical behavior in comparison with other materials when simulating in vitro load resistance of a fixation method established for sagittal split ramus osteotomy (SSRO). Thirty synthetic and standardized human hemimandible replicas with SSRO were divided into three groups of 10 samples each. Group A-ABS plastic; Group B-polyamide; and Group C-polyurethane. These were fixated with three bicortical position screws (16 mm in length, 2.0-mm system) in an inverted l pattern using perforation guide and 5-mm advancement. Each sample was submitted to linear vertical load, and load strength values were recorded at 1, 3, 5, 7, and 10 mm of displacement. The means and standard deviation were compared using the analysis of variance (p < 0.05) and the Tukey test. A tendency for lower values was observed in Group B in comparison with Groups A and C. At 3 and 5 mm of displacement, a difference between Groups A and C was found in comparison with Group B (p < 0.05). At 7 and 10 mm of displacement, a difference was found among the three groups, in which Group C showed the highest values and Group B the lowest (p < 0.05). Taking into consideration the results obtained and the behavior of each material used as a substrate, significant differences occurred among the materials when compared among them. PMID- 26269725 TI - Lessons Learned in Scalp Reconstruction and Tailoring Free Tissue Transfer in the Elderly: A Case Series and Literature Review. AB - This article aims to demonstrate an individualized approach to an elderly patient requiring scalp reconstruction, to describe the methodology in flap selection, lessons learned, and report outcomes. A retrospective review of a single surgeon's experience of scalp reconstruction (E. D. R.) using free tissue transfer from 2005 to 2011, in patients older than 70 years, was completed. A total of eight patients met the inclusion criteria, five males and three females, with a mean age of 80.4 years (range, 73-92). Free tissue transfer achieved 100% soft tissue coverage. Six of the eight patients required cranioplasty. The mean size calvarial defect was 92 cm(2) (range, 35-285 cm(2)). The mean flap size was 117.6 cm(2) (range, 42-285 cm(2)). Free flaps included three ulnar, three anterolateral thigh, one latissimus dorsi, and one thoracodorsal perforator flap. The mean follow-up time was 18.4 months (range, 3-46 months). Donor site morbidity was minimal. Mortality was 0%. Immediate flap failure was 0%. Other complications occurred in six of the eight patients. Mean revisionary procedures were 1.25 procedures per patient. It was concluded that chronological age does not increase mortality or catastrophic flap complications; however, morbidity is increased in the elderly and revisionary surgery is likely. PMID- 26269726 TI - Delayed Cranioplasty: Outcomes Using Frozen Autologous Bone Flaps. AB - Reconstruction of skull defects following decompressive craniectomy is associated with a high rate of complications. Implantation of autologous cryopreserved bone has been associated with infection rates of up to 33%, resulting in considerable patient morbidity. Predisposing factors for infection and other complications are poorly understood. Patients undergoing cranioplasty between 1999 and 2009 were identified from a prospectively maintained database. Records and imaging were reviewed retrospectively. Demographics, the initial craniectomy and subsequent cranioplasty surgeries, complications, and outcomes were recorded. A total of 187 patients underwent delayed cranioplasty using autologous bone flaps cryopreserved at -30 degrees C following decompressive craniectomy. Indications for craniectomy were trauma (77.0%), stroke (16.0%), subarachnoid hemorrhage (2.67%), tumor (2.14%), and infection (2.14%). There were 64 complications overall (34.2%), the most common being infection (11.2%) and bone resorption (5.35%). After multivariate analysis, intraoperative cerebrospinal fluid (CSF) leak was significantly associated with infection, whereas longer duration of surgery and unilateral site were associated with resorption. Cranioplasty using frozen autologous bone is associated with a high rate of infective complications. Intraoperative CSF leak is a potentially modifiable risk factor. Meticulous dissection during cranioplasty surgery to minimize the chance of breaching the dural or pseudodural plane may reduce the chance of bone flap. PMID- 26269727 TI - Orbital Roof Fractures: A Clinically Based Classification and Treatment Algorithm. AB - Orbital roof fractures are relatively uncommon in craniofacial surgery but present a management challenge due to their anatomy and potential associated injuries. Currently, neither a classification system nor treatment algorithm exists for orbital roof fractures, which this article aims to provide. This article provides a literature review and clinical experience of a tertiary trauma center in Australia. All cases admitted to the Royal Melbourne Hospital with orbital roof fractures between January 2011 and July 2013 were reviewed regarding patient characteristics, mechanism, imaging (computed tomography), and management. Forty-seven patients with orbital roof fractures were treated. Three of these were isolated cases. Forty were male and seven were female. Assault (14) and falls (13) were the most common causes of injury. Forty-two patients were treated conservatively and five had orbital roof repairs. On the basis of the literature and local experience, we propose a four-point system, with subcategories allowing for different fracture characteristics to impact management. Despite the infrequency of orbital roof fractures, their potential ophthalmological, neurological, and functional sequelae can carry a significant morbidity. As such, an algorithm for management of orbital roof fractures may help to ensure appropriate and successful management of these patients. PMID- 26269728 TI - Early Experience with Biodegradable Fixation of Pediatric Mandibular Fractures. AB - This clinical study aims to evaluate the stability and efficiency of biodegradable self-reinforced poly-l/dl-lactide (SR-PLDLA) plates and screws for fixation of pediatric mandibular fractures. The study included 12 patients (3-12 years old) with 14 mandibular fractures. They were treated by open reduction and internal fixation by SR-PLDLA plates and screws. Maxillomandibular fixation was maintained for 1 week postoperatively. Clinical follow-up was performed at 1 week, 6 weeks, 3 months, and 12 months postoperatively. Radiographs were done at 1 week, 3 months, and 12 months postoperatively to observe any displacement and fracture healing. All fractures healed both clinically and radiologically. No serious complications were reported in the patients. Normal occlusion was achieved in all cases. Biodegradable osteofixation of mandibular fractures offers a valuable clinical solution for pediatric patients getting the benefit of avoiding secondary surgery to remove plates, decreasing the hospital stay, further painful procedures, and psychological impact. PMID- 26269729 TI - Computer-Assisted Three-Dimensional Planning for Orbital Decompression. AB - Thyroid-associated orbitopathy is the most common cause of unilateral or bilateral proptosis in adults. A mainstay of surgical treatment is orbital decompression utilizing osteotomies to increase the size of the affected bony orbit to accommodate the larger soft tissue volume. Over the past several decades, numerous approaches have been described for orbital decompression. However, given the intricate osseous and soft tissue anatomy within the orbit, orbital decompression is a potentially hazardous intervention. With advances in three-dimensional imaging and virtual planning, extensive orbital decompressions can be performed safely and efficiently. In this report, we describe two cases of three-wall orbital decompressions using three-dimensional planning. PMID- 26269730 TI - Pneumosinus Dilatans Helping Subcranial Resection in a Patient with Advanced Ethmoid Malignancy. AB - Subcranial approach is a useful procedure in the management of limited anterior skull base tumors. But the posterior and superior visualization may be limited, in ethmoid malignancies with a large intracranial extension. A 55-year-old male patient, a case of an ethmoid malignancy, with a large intracranial component was resected with adequate margins by a subcranial approach. The coincident pneumosinus dilatans helped the surgical resection. This case demonstrates that assessment of pneumatization of the frontal sinus is as important as the size and extent of the tumor, while deciding an anterior skull base surgical approach. Even large malignant lesions may be approached subcranially if the frontal sinus is proportionately large. Pneumosinus dilatans, though rare, can be used to the benefit of the patient in selecting a less invasive approach. PMID- 26269731 TI - Acute Intraorbital Hemorrhage following Reduction of a Displaced Orbitozygomaticomaxillary Complex Fracture. AB - Orbitozygomaticomaxillary complex (OZMC) fractures are commonly encountered by the craniomaxillofacial trauma surgeon and may, in fact, be the most common type of orbital fracture. Disruption of articulation with the frontal and sphenoid bones causes disruption of the internal orbital skeleton, which can result in diplopia from extraocular muscle swelling or entrapment, or enophthalmos from increased orbital volume. Although there is significant energy transferred to the orbit in these injuries, blindness and intraorbital hematoma are, fortunately, relatively rare complications, typically seen pre- or postoperatively. In this report, we describe the development of acute intraorbital hemorrhage following reduction of a displaced OZMC fracture. PMID- 26269732 TI - Management of Ossifying Fibroma in a Suspicious Case of Hyperparathyroid-Jaw Tumor Syndrome. AB - The purpose of this article is to report a case of ossifying fibroma in the mandible associated with hyperparathyroid-jaw tumor syndrome, in a 46-year-old Caucasian female, surgically resected and reconstructed with iliac crest bone, followed by implant placement. This is a rare syndrome with an autosomal dominant pattern, with the development of primary hyperparathyroidism mainly due to parathyroid adenomas. Fibro-osseous lesions in the jaws can be present and can also precede the development of the endocrine disorder. As renal abnormalities and uterine tumors can develop, an interdisciplinary approach is imperative for its diagnosis and management, due to the possibility of recurrence and potential for malignancy. PMID- 26269733 TI - Temporal Approach to Removal of a Large Orbital Foreign Body. AB - Accidents with firearms can result in extensive orbital trauma. Moreover, gun parts can come loose and impale the maxillofacial region. These injuries can cause the loss of visual acuity and impair eye movements. Multidisciplinary treatment is required for injuries associated with this type of trauma. Computed tomography with three-dimensional reconstruction is useful for determining the precise location and size of the object lodged in the facial skeleton, thereby facilitating the planning of the correct surgical approach. The temporal approach is a fast, simple technique with few complications that is indicated for access to the infratemporal fossa. This article describes the use of the temporal approach on a firearm victim in whom the breech of a rifle had impaled orbital region, with the extremity lodged in the infratemporal fossa. PMID- 26269734 TI - Carotid-Cavernous Fistula as a Complication of Facial Trauma: A Case Report. AB - Posttraumatic carotid-cavernous fistula is a very rare complication that can occur in patients with craniomaxillofacial trauma. Symptoms involve headache, diplopia, ptosis of the upper lid, conjunctival chemosis, pulsating exophthalmos, and ophthalmoplegia. Diagnosis can be challenging because various pathologic entities can present with similar symptoms such as superior orbital fissure syndrome, orbital apex syndrome, retrobulbar hematoma, and cavernous sinus syndrome. However, accurate and early diagnosis is of utmost importance because treatment delay may lead to blindness or permanent neurologic deficits. In this article, a case of posttraumatic carotid-cavernous fistula that was twice misdiagnosed is presented. PMID- 26269735 TI - Circummandibular Wires for Treatment of Dentoalveolar Fractures Adjacent to Edentulous Areas: A Report of Two Cases. AB - In general, dentoalveolar fractures are a common injury seen in emergency departments, dental offices, and oral and maxillofacial surgery practices. These injuries can be the result of direct trauma or indirect trauma. Direct trauma more often causes trauma to the maxillary dentition due to the exposure of the maxillary anterior teeth. Indirect trauma is usually the result of forced occlusion secondary to a blow to the chin or from a whiplash injury. Falls are the most common mechanism of injury seen in the pediatric group. In adolescents, many of these fractures are sustained during sporting activities. However, the use of mouth guards and other protective equipment has decreased this number. Most adult injuries are caused by motor vehicle accidents, contact sports, falls, bicycles, interpersonal violence, medical/dental mishaps, and industrial accidents. Early intervention to reduce and stabilize the fracture is required to establish a bony union and ensure correct function. Most dentoalveolar fractures have bilateral stable adjacent dentition and are treated with a closed technique utilizing an acid-etch/resin splint followed by splint removal at 4 weeks. Other inferior stabilization treatments used are arch bars and other wiring techniques. It is widely accepted that semirigid stabilization techniques, such as an acid etch/resin splint or wiring procedures, are adequate to treat dentoalveolar fractures. This is in contrast to the treatment of mandible fractures where AO principles of rigid fixation are often followed. Fractures that are unable to be reduced sometimes necessitate an open reduction followed by internal fixation, sometimes using a secondary splint for mobile teeth. In those rare cases when there are not stable adjacent teeth bilaterally other modalities must be considered. In the present report, two cases are presented where circummandibular wires were used to treat fractured mandibular dentoalveolar segments adjacent to edentulous areas. PMID- 26269736 TI - Posttraumatic Delayed Enophthalmos: Analogies with Silent Sinus Syndrome? Case Report and Literature Review. AB - Acute posttraumatic enophthalmos is a well-known symptom occurring in orbital blowout fractures. Its late onset in the absence of radiologic evidence of displaced fractures is rare and traditionally attributed to ischemic liponecrosis or fibrotic scarring of endo-orbital soft tissues. In this article, we describe a case of facial trauma, diagnosed and treated at the Maxillo-Facial Surgical Department of Hospital Ca' Granda Niguarda of Milan, in which delayed monolateral enophthalmos is associated with CT evidence of remodeling of orbital walls attributed to atelectasis of the maxillary sinus, as occurs spontaneously in patients suffering from silent sinus syndrome (SSS). Despite that classic criteria exclude traumatic etiology of SSS, recent literature suggests the possibility to include it. Our case is the first reported in literature supported by complete clinical and radiological documentation obtained before and after the condition established itself. The analogy with cases of spontaneous obstacle of aeration allows us to choose "two-step" surgical treatment with endoscopic uncinectomy and antrostomy and a delayed surgical correction of orbital volume to improve aesthetic results. The case described in this article and the review of the literature may focus physicians' attention on evaluating the possible traumatic changes in the physiologic sinus drainage system. PMID- 26269737 TI - Management Issues in the Treatment of an Ameloblastoma with an Atypical Presentation. AB - Benign ameloblastoma (BA) is the most common tumor arising from the odontogenic epithelium. Surgical resection with adequate margins is the mainstay of treatment due to the high index of tumor recurrence when not completely excised. Although locoregional spread has been described in the literature, it is very uncommon. We describe the treatment and follow-up of a 22-year-old woman with multiple recurrences and locoregional spread of a mandibular ameloblastoma who was referred to our center after several tumor resections with subsequent reconstructions. After a complete macroscopical removal of a new recurrence, the mandible was primarily reconstructed. A local homolateral recurrence and a second lesion in the contralateral maxilla were detected after 1-year follow-up and accordingly treated. After 4 years the patient showed a new tumor in the temporal fossa and was reoperated. The histopathology was consistent with a BA in all cases. Even though it is rare, locoregional spread of BA has been reported previously. Recurrences discovered during follow-up may require further resections. A close follow-up is mandatory, and treatment of these cases may result demanding requiring a multiple team approach, including oncologists and radiotherapists. PMID- 26269738 TI - Erratum: Measuring autistic traits in the general population: a systematic review of the Autism-Spectrum Quotient (AQ) in a nonclinical population sample of 6,900 typical adult males and females. AB - [This corrects the article DOI: 10.1186/2040-2392-6-2.]. PMID- 26269739 TI - In developed countries male circumcision prevalence is inversely related to HIV prevalence. AB - A study by Chemtob and co-workers found significantly lower prevalence of HIV amongst heterosexual men and women in Israel compared with the Netherlands and France. Risk factors for heterosexual HIV infection in these countries were similar, apart from one, namely, a strikingly higher prevalence of male circumcision (MC) in Israel compared with the Netherlands and France. It is now well established that MC protects heterosexual men against becoming infected with HIV during sexual intercourse with an infected woman. In epidemic settings, such as countries in sub-Saharan Africa, in which heterosexual contact is the primary driver for HIV infection, MC is being implemented to reduce HIV prevalence. The results of the new study by Chemtob and co-workers support the evidence and recent polices in the United States advocating MC to reduce the spread of HIV. While prevalence in developed countries is generally low, it is rising. In the long term, neonatal MC is the most desirable option, since not only is it simpler, safer, cheaper and more convenient than MC later, it provides immediate protection from infections, penile inflammation, genital cancers and physical problems. It is also cost-effective. European countries have not supported MC for its public health benefits. The new findings add to calls for European and other countries with low MC prevalence to consider developing evidence-based policies favoring MC in order to reduce HIV and other infections and diseases and at the same time reduce suffering, mortality and the cost of treating these. PMID- 26269740 TI - Health information technology implementation - impacts and policy considerations: a comparison between Israel and Portugal. AB - The use of Information and Communications Technology (ICT) in health systems is increasing worldwide. While it is assumed that ICT holds great potential to make health services more efficient and grant patients more empowerment, research on these trends is at an early stage. Building on a study of the impact of ICT on physicians and patients in Israel, a Short Term Scientific Mission (STSM) sponsored by COST Net in conjunction with CIES/ISCTE IUL (Portugal) facilitated a comparison of ICT in health in Israel and Portugal. The comparison focused on patient empowerment, physician behavior and the role of government in implementing ICT. The research in both countries was qualitative in nature. In depth interviews with the Ministry of Health (MOH), the private sector, patients associations, health plans and researchers were used to collect data. Purposeful sampling was used to select respondents, and secondary sources were used for triangulation. The findings indicate that respondents in both countries feel that patient empowerment has indeed been furthered by introduction of ICT. Regarding physicians, in both countries ICT is seen as providing more information that can be used in medical decision making. Increased access of patients to web-based medical information can strengthen the role of patients in decision making and improve the physician-patient relationship, but also shift the latter in ways that may require adjustments in physician orientation. Physician uptake of ICT in both countries involves overcoming certain barriers, such as resistance to change. At the national level, important differences were found between the two countries. While in Israel, ICT was promoted and adopted by the meso level of the health system, in particular the health plans and government intervention can be found in a later stage, in Portugal the government was the main developer and national strategies were built from the beginning. These two approaches present different advantages and disadvantages. Government involvement in earlier stages could provide benefit in terms of interoperability of systems between different healthcare organizations. However, innovation could be slowed down due to government bureaucracy or lack of leadership. The work provides information in order to understand and improve ICT services. Additionally, it provides input regarding impact of ICT on the physician/patient relationship and national policies in the area. PMID- 26269741 TI - Collection media and delayed freezing effects on microbial composition of human stool. AB - BACKGROUND: Different bacteria in stool have markedly varied growth and survival when stored at ambient temperature. It is paramount to develop optimal biostabilization of stool samples during collection and assess long-term storage for clinical specimens and epidemiological microbiome studies. We evaluated the effect of collection media and delayed freezing up to 7 days on microbial composition. Ten participants collected triplicate stool samples each into no media as well as RNAlater(r) with and without kanamycin or ciprofloxacin. For each set of conditions, triplicate samples were frozen on dry ice immediately (time = 0) or frozen at -80 degrees C after 3-days and 7-days incubation at 25 degrees C. Microbiota metrics were estimated from Illumina MiSeq sequences of 16S rRNA gene fragments (V3-V4 region). Intraclass correlation coefficients (ICC) across triplicates, collection media, and incubation time were estimated for taxonomy and alpha and beta diversity metrics. RESULTS: RNAlater(r) alone yielded the highest ICCs for diversity metrics at time = 0 [ICC median 0.935 (range 0.89 0.97)], but ICCs varied greatly (range 0.44-1.0) for taxa with relative abundances <1%. The 3- and 7-day freezing delays were generally associated with stable beta diversity for all three media conditions. Freezing delay caused increased variance for Shannon index (median ICC 0.77) and especially for observed species abundance (median ICC 0.47). Variance in observed species abundance and in phylogenetic distance whole tree was similarly increased with a 7-day delay. Antibiotics did not mitigate variance. No media had inferior ICCs at time 0 and differed markedly from any media in microbiome composition (e.g., P =0.01 for relative abundance of Bacteroidetes). CONCLUSION: Bacterial community composition was stable for 7 days at room temperature in RNAlater(r) alone. RNAlater(r) provides some stability for beta diversity analyses, but analyses of rare taxa will be inaccurate if specimens are not frozen immediately. RNAlater(r) could be used as collection media with minimal change in the microbiota composition. PMID- 26269742 TI - Prevalence and risk factors associated with malaria infection among pregnant women in a semi-urban community of north-western Nigeria. AB - BACKGROUND: Malaria during pregnancy remains a serious public health problem, with substantial risks for the mother, her foetus and the newborn. The aim of this study was to determine the prevalence of malaria and possible risk factors for malaria infection among pregnant women in a semi-urban area in north-western Nigeria. Pregnant women are among the most susceptible to malaria infection. Knowledge of their malaria infection status is an important yardstick to measure the effectiveness of any malaria control programme. METHODS: We conducted a cross sectional study in the semi-urban area of Argungu, Kebbi State Nigeria. Two hundred and fifty five pregnant women were included in the study after informed verbal consent was obtained. For each participant, the socio-demographic profile, stage of pregnancy and attitude to the use of insecticide- treated nets (ITNs) were investigated using a questionnaire. Peripheral blood samples were collected and thick blood smears were prepared and stained with Giemsa stains to check for malaria parasitaemia. The associations between age, education level and use of ITNs with occurrence of malaria infection during pregnancy were analysed using the chi-square test. RESULTS: One hundred and six (41.6%) out of 255 pregnant women were infected with malaria parasites, with a mean parasite density of 800 parasitesMUl(-1). It was found that prevalence and parasite density decreased as age increased. The chi-square test indicated that a lack of education and non usage of ITNs were significantly associated with malaria infection. CONCLUSION: Malaria is still a major public health issue among pregnant women mainly due to illiteracy and non -compliance to using ITNs. Increasing awareness about malaria preventive measures and early attendance of antenatal care services will help to reduce malaria and, consequently, its associated morbidities and mortalities. PMID- 26269743 TI - Neuropsychological assessment in adolescents with anorexia nervosa - exploring the relationship between self-report and performance-based testing. AB - OBJECTIVE: Research investigating the relationship between neuropsychological test performances and self-reported cognitive functioning in patients with anorexia nervosa (AN) is limited, and existing experimental studies only demonstrate a low-to-moderate relationship between the performance based tests and everyday behaviour. The objective of the current study was to explore the association between neuropsychological test performance and self-reports of executive functioning in adolescents with AN. METHOD: Twenty adolescent females diagnosed with AN, aged 13 to 18, completed neuropsychological test battery "the Ravello Profile" and the self-report version of the Behaviour Rating Inventory of Executive Function (BRIEF-SR). The BRIEF Parent Form (BRIEF-PF) was employed to provide additional information of the patients' executive functioning. RESULTS: Based on group level analyses, the results support the existing literature in failing to find consistent weaknesses in neuropsychological functioning in adolescents with AN. Further, with few exceptions, the Ravello Profile was insubstantially correlated with the majority of the BRIEF clinical scales, indicative of a lack of association between these two assessment methods. CONCLUSION: The current study accentuates the need for concern regarding the generalizability of neuropsychological assessments in adolescent patients with AN. PMID- 26269744 TI - Development of a high-field MR-guided HIFU setup for thermal and mechanical ablation methods in small animals. AB - BACKGROUND: Thermal and mechanical high intensity focused ultrasound (HIFU) ablation techniques are in development for non-invasive treatment of cancer. However, knowledge of in vivo histopathologic and immunologic reactions after HIFU ablation is still limited. This study aims to create a setup for evaluation of different HIFU ablation methods in mouse tumors using high-field magnetic resonance (MR) guidance. An optimized MR-guided-HIFU setup could be used to increase knowledge of the different pathologic and immunologic reactions to different HIFU ablation methods. METHODS: Three different HIFU treatment strategies were applied in mouse melanomas (B16): a thermal (continuous wave), a mechanical (5 ms pulsed wave), and an intermediate setting (20 ms pulsed wave) for HIFU ablation, all under MR guidance using a 7 tesla animal MR system. Histopathologic evaluation was performed 3 days after treatment. RESULTS: The focus of the ultrasound transducer could accurately be positioned within the tumor under MR image guidance, without substantial damage to the surrounding tissue and skin. All mice retained complete use of the treated leg after treatment. Temperatures of >60, <50, and <44 degrees C were reached during thermal, intermediate, and mechanical HIFU ablation, respectively. Thermal treated tumors showed large regions of coagulative necrosis. Tumors of both the mechanical and intermediate groups showed fractionated tissue with islands of necrosis and some pseudocysts with hemorrhage. CONCLUSION: A stable small animal MR-guided HIFU setup was designed and evaluated for follow-up MR imaging and histopathologic responses of the treated tumors. This will facilitate further studies with a larger number of mice for detailed evaluation of the pathologic and immunologic response to different HIFU strategies. PMID- 26269745 TI - The clinical relevance of plasma potassium abnormalities on admission in trauma patients: a retrospective observational study. AB - BACKGROUND: Abnormalities in potassium levels can lead to several clinical difficulties in trauma patients admitted to the ICU. However, the significance of potassium abnormalities soon after admission in trauma patients has not yet been clearly delineated. The objective of this study was to describe the plasma potassium abnormalities in trauma patients on admission and to examine the clinical outcomes associated with these abnormalities. METHODS: We performed a retrospective observational study of plasma potassium levels in trauma patients admitted to the Fukuyama City Hospital between January 1, 2010 and December 31, 2013. Five hundred twenty consecutive trauma patients were included and categorized into six groups according to their plasma potassium level on admission (<3.0, 3.0-<3.5, 3.5-<4.0, 4.0-<4.5, 4.5-<5.0, and >=5.0 mEq/L). After adjusting for covariates, including age, gender, the Revised Trauma Score, and the Injury Severity Score, logistic regression analysis was used to examine the association between plasma potassium levels and outcomes, including life-saving interventions and in-hospital mortality. RESULTS: Two hundred twenty-seven patients (43.7 %) presented with hypokalemia (<3.5 mEq/L), while seven patients (1.3 %) presented with hyperkalemia (>=5.0 mEq/L). Patients in the lowest potassium group (<3.0 mEq/L, n = 36 [6.9 %]) were significantly associated with craniotomy (adjusted odds ratio 5.25 [95 % confidence interval 2.06-13.40]; p < 0.001) and showed an increased trend toward in-hospital mortality. In the second lowest potassium group (3.0-< 3.5 mEq/L, n = 191 [36.7 %]), the adjusted odds ratio for craniotomy was significantly higher (2.03 [95 % confidence interval 1.01-4.07]; p = 0.048) compared to the reference group. CONCLUSIONS: Trauma patients presenting with hypokalemia (<3.5 mEq/L) on admission may be associated with severe head trauma requiring life-saving craniotomy. PMID- 26269746 TI - CFD modeling of incinerator to increase PCBs removal from outlet gas. AB - Incineration of persistent organic pollutants (POPs) is an important alternative way for disposal of this type of hazardous waste. PCBs are very stable compounds and do not decompose readily. Individuals can be exposed to PCBs through several ways and damaged by their effects. A well design of a waste incinerator will convert these components to unharmfull materials. In this paper we have studied the design parameters of an incinerator with numerical approaches. The CFD software Fluent 6.3 is used for modelling of an incinerator. The effects of several baffles inside the incinerator on flow distribution and heat is investigated. The results show that baffles can reduce eddy flows, increase retaining times, and efficiencies. The baffles reduced cool areas and increased efficiencies of heat as maximum temperature in two and three baffle embedded incinerator were 100 and 200 degrees C higher than the non-baffle case, respectively. Also the gas emission leaves the incinerator with a lower speed across a longer path and the turbulent flow in the incinerator is stronger. PMID- 26269747 TI - Coronary artery calcification, cardiovascular events, and death: a prospective cohort study of incident patients on hemodialysis. AB - BACKGROUND: Coronary calcification in patients with end-stage renal disease (ESRD) is associated with an increased risk of cardiovascular outcomes and death from all causes. Previous evidence has been limited by short follow-up periods and inclusion of a heterogeneous cluster of events in the primary analyses. OBJECTIVE: To describe coronary calcification in patients incident to ESRD, and to identify whether calcification predicts vascular events or death. DESIGN: Prospective substudy of an inception cohort. SETTING: Tertiary care haemodialysis centre in Ontario (St Joseph's Healthcare Hamilton). PARTICIPANTS: Patients starting haemodialysis who were new to ESRD. MEASUREMENTS: At baseline, clinical characterization and spiral computed tomography (CT) to score coronary calcification by the Agatston-Janowitz 130 scoring method. A primary outcome composite of adjudicated stroke, myocardial infarction, or death. METHODS: We followed patients prospectively to identify the relationship between cardiac calcification and subsequent stroke, myocardial infarction, or death, using Cox regression. RESULTS: We recruited 248 patients in 3 centres to our main study, which required only biochemical markers. Of these 164 were at St Joseph's healthcare, and eligible to participate in the substudy; of these, 51 completed CT scanning (31 %). Median follow up was 26 months (Q1, Q3: 14, 34). The primary outcome occurred in 16 patients; 11 in the group above the median and 5 in the group below (p = 0.086). There were 26 primary outcomes in 16 patients; 20 (77 %) events in the group above the coronary calcification median and 6 (23 %) in the group below (p = 0.006). There were 10 deaths; 8 in the group above the median compared with 2 in the group below (p = 0.04). The hazard ratios for coronary calcification above, compared with below the median, for the primary outcome composite were 2.5 (95 % CI 0.87, 7.3; p = 0.09) and 1.7 (95 % CI 0.55, 5.4; p = 0.4), unadjusted and adjusted for age, respectively. For death, the hazard ratios were 4.6 (95 % CI 0.98, 21.96; p = 0.054) and 2.4 (95 % CI 0.45, 12.97; p = 0.3) respectively. LIMITATIONS: We were limited by a small sample size and a small number of events. CONCLUSIONS: Respondent burden is high for additional testing around the initiation of dialysis. High coronary calcification in patients new to ESRD has a tendency to predict cardiovascular outcomes and death, though effects are attenuated when adjusted for age. PMID- 26269748 TI - Systems biology from virus to humans. AB - Natural infection and then recovery are considered to be the most effective means for hosts to build protective immunity. Thus, mimicking natural infection of pathogens, many live attenuated vaccines such as influenza virus, and yellow fever vaccine 17D were developed and have been successfully used to induce protective immunity. However, humans fail to generate long-term protective immunity to some pathogens after natural infection such as influenza virus, respiratory syncytial virus (RSV), and human immunodeficiency virus (HIV) even if they survive initial infections. Many vaccines are suboptimal since much mortality is still occurring, which is exampled by influenza and tuberculosis. It is critically important to increase our understanding on protein components of pathogens and vaccines as well as cellular and host responses to infections and vaccinations. Here, we highlight recent advances in gene transcripts and protein analysis results in the systems biology to enhance our understanding of viral pathogens, vaccines, and host cell responses. PMID- 26269750 TI - PC4 induces lymphangiogenesis dependent VEGF-C/VEGF-D/VEGFR-3 axis activation in lung adenocarcinoma. AB - Human transcriptional positive cofactor 4 (PC4) is a novel marker for diagnosis and treatment of advanced human cancers metastasis. In human lung adenocarcinoma, tumor lymphangiogenesis, an important early event, can promotes lymphatic metastasis, while it has been reported that VEGF-C/VEGF-D/VEGFR-3 axis plays an important role in lymphangiogenesis. The proposed study aims to explore whether PC4 correlates with VEGF-C/VEGF-D/VEGFR-3 axis of lymphangiogenesis in the lymph node metastasis during lung adenocarcinoma. Here, small interfering RNA technique was employed to investigate the relationship of PC4 and the VEGF-C/VEGF-D/VEGFR-3 axis in lung adenocarcinoma cell lines as well as tumor xenografts of mice model. And then mRNA and protein levels of PC4, VEGF-C, VEGF-D and VEGFR-3 were analyzed. Moreover, the correlation between PC4 expression and lymphatic vessel density or the rate of metastatsis in vivo was also revealed. Down-regulating PC4 expression resulted in the lower expression of VEGFC, VEGF-D and VEGFR-3 in mRNA and protein levels, and PC4 expression was significantly related with the factor of VEGF-C/VEGF-D/VEGFR-3 axis expression (P<0.05). Meanwhile, high expression level of PC4 was accompanied by the higher density of tumor lymphatic vessels and the rate of metastatsis in vivo (P<0.05). PC4 expression correlated with the levels of VEGF-C, VEGF-D and VEGFR-3 during the development of lymphangiogenesis and lymphatic metastasis in lung adenocarcinoma in vitro and in vivo, which may be a novel marker in the development of lymphangiogenesis and lymphatic metastasis of tumors. PMID- 26269749 TI - Nek6 and Hif-1alpha cooperate with the cytoskeletal gateway of drug resistance to drive outcome in serous ovarian cancer. AB - Hypoxia selects the most aggressive and drug-resistant clones in solid malignancies. One of the pivotal transcription factors induced by hypoxia is Hif 1alpha. However, in serous ovarian cancer (SEOC), Hif-1alpha expression is not a prognostic biomarker. This study aims to assess the hypothesis that the serine threonine kinase Nek6 functions as a downstream effector cooperating with Hif 1alpha in driving ovarian cancer aggressiveness. Nek6 was overexpressed and Hif 1alpha was silenced in A2780 cells. Nek6 was also stably silenced in Hey cells. The dependence of Nek6 expression on Hif-1alpha was assayed as a function of hypoxic growth conditions. Nek6 interaction with the cytoskeletal gateway of drug resistance was investigated with far western blot. The co-expression of NEK6, HIF1A, TUBB3 and GBP1 transcripts was quantified with qPCR in two cohorts of SEOC patients (346 locally treated patients and 344 from the TCGA dataset). Nek6 expression is induced by hypoxia in a Hif-1alpha dependent fashion. Nek6 directly interacts with GBP-1, thus being a component of the cytoskeletal gateway of drug resistance. Nek6 overexpression increases and silencing decreases the anchorage independent growth of cultured cells. In SEOC patients, NEK6 expression is significantly correlated with HIF1A. Co-expression of NEK6, HIF1A, TUBB3 and GBP1 transcripts identifies a subset of SEOC patients characterized by poor outcome and drug resistance. This study demonstrates the functional relevance of Nek6 in the context of the adaptive response to hypoxia in SEOC. This finding may help identify a sub-population of patients at high risk of relapse to standard first line chemotherapy. PMID- 26269751 TI - TGF-beta induces fascin expression in gastric cancer via phosphorylation of smad3 linker area. AB - BACKGROUND: Fascin is an actin-bundling protein critical for tumor invasion. TGF beta could induce fascin expression in gastric cancer cells. In this study, we attempted to explore the role of p-smad3L in the expression of fascin induced by TGF-beta in gastric cancer cells. METHODS: Pseudopodia were evaluated by immunofluorescence. Fascin expression was detected by RT-PCR and western blot. Smad3 siRNA was used to repress the endogenous smad3. The phosphorylations of smad3 linker region at sites s204, s208 and s213 were detected by western blot. The fascin promoter reporter activity was measured by dual luciferase assay. RESULTS: TGF-beta could increase the formation of pseudopodia and the expression of fascin in gastric cancer cells. Smad3 depletion abrogated the expression of fascin induced by TGF-beta. The phosphorylation of smad3 linker region at serine 204, 208 and 213 was enhanced in gastric cancer cells after TGF-beta treatment. The fascin promoter reporter activity was significantly enhanced with TGF-beta treatment in both wild-type Smad3 group and Smad3EPSM group (P<0.05). Furthermore, the fascin promoter reporter activity in the wild-type Smad3 transfectant cells was significantly higher than that in Smad3EPSM cells (P<0.05). CONCLUSIONS: fascin expression induced by TGF-beta depends on smad3, at least in part, depends on smad3 linker phosphorylation. PMID- 26269752 TI - Quantitative DNA hypomethylation of ligand Jagged1 and receptor Notch1 signifies occurrence and progression of breast carcinoma. AB - Methylation alterations of Jagged1 and Notch1 genes have been reported in non tumor lesions and a few cancers. However, methylation profiles of Jagged1 promoter and Notch1 exon25 in breast cancer and matched normal tissue and the association of methylation with clinicopathological characteristics still remain unclear. To explore the potential effects of aberrant DNA methylation of Jagged1 and Notch1 on occurrence and progression of breast cancer, we detected the quantitative DNA methylation of Jagged1 and Notch1 in 73 breast cancer (BC) and 20 adjacent normal breast tissues (ANBT) by using MassARRAY spectrometry. The methylation level of overall and majority individual CpG sites of the two genes were synergistically significantly lower in BC than in ANBT. The overall hypomethylation of the two genes, particularly of Jagged1 CpG_8.9.10 and Notch1 CpG_14.15.16 in primary tumors, were markedly associated with lymph node metastasis, advanced stage and high grade. The protein expressions of the both genes were examined by immunohistochemical staining in same cohorts. The expression was significantly inverse correlation with methylation. The two proteins in primary tumor were synergistically up-regulated and dramatically related to lymph node metastasis, advanced stage and high grade. Our findings suggest that the synergetic hypomethylation of Jagged1 and Notch1 genes, especially of Jagged1 CpG_8.9.10 and Notch1 CpG_14.15.16, may involve tumorigenesis and development of breast cancer. The negative relationship between methylation and expression indicates methylation role for expression regulation. The synergetic overexpression of the two proteins further indicates the effects on occurrence and progression of breast cancer. PMID- 26269753 TI - Silencing of Wnt10B reduces viability of heptocellular carcinoma HepG2 cells. AB - Dysregulation of Wnt-mediated beta-catenin signaling is associated with carcinogenesis and progression of hepatocellular carcinoma (HCC). Our previous studies showed that the Wnt10B gene, a member of Wnt gene family, over-activated in HCC tissues and cells. Here we demonstrate that stable silencing of Wnt10B reduces the viability of HCC cells in culture. HepG2, a human HCC cell line, was cultured in vitro and Wnt10B gene in the cells stably silenced, as showed in Western blotting analysis, by the shRNA interference with lentivirus plasmid transfection. Compared to the control (HepG2 cells without Wnt10B silencing), the Wnt10B-silencing cells showed significant reductions in proliferation, colony formation, migration and invasion. Furthermore, serum deprivation-induced apoptotic death, assessed by Hoechst 33342 staining and fluorescent microscopy, increased significantly in the Wnt10B-silencing cells. FACScan analysis indicated an arrest of the cell cycle in the Wnt10B-silencing HCC cells, with significant increases in the number of cells in G0-G1 and S phases. Thus, we hypothesize that Wnt10B plays an oncogenic role in HCC and is a potential therapeutic target. PMID- 26269755 TI - Transcription factor KLF4 regulates microRNA-544 that targets YWHAZ in cervical cancer. AB - The deregulation of microRNAs has been demonstrated in various tumor processes. Here, we report that microRNA-544 (miR-544) is decreased in cervical cancer tissues compared with normal cervical tissues. To identify the mechanisms involved in miR-544 deregulation, we studied the regulation of miR-544 expression at the transcriptional level. We first identified the transcriptional start site of miR-544 by 5' rapid amplification of cDNA ends and subsequently determined the miR-544 promoter. We discovered that the transcription factor Krueppel-like factor 4 (KLF4) is involved in the transcriptional regulation of miR-544 through interaction with the miR-544 promoter. In addition, we found that miR-544 directly targets the YWHAZ oncogene and functions as a tumor suppressor in cervical cancer cells. miR-544 is involved in cell cycle regulation and suppresses cervical cancer cell proliferation, colony formation, migration and invasion in a manner associated with YWHAZ downregulation. In summary, our findings demonstrate that KLF4 upregulates miR-544 transcription by activating the miR-544 promoter and that miR-544 functions as a tumor suppressor by targeting YWHAZ. Therefore, miR-544 may be a potential novel therapeutic target and prognostic marker for cervical cancer. PMID- 26269754 TI - Establishment and characterization of cetuximab resistant head and neck squamous cell carcinoma cell lines: focus on the contribution of the AP-1 transcription factor. AB - BACKGROUND: After an initial response to EGFR targeted therapy, secondary resistance almost invariably ensues, thereby limiting the clinical benefit of the drug. Hence, it has been recognized that the successful implementation of targeted therapy in the treatment of HNSCC cancer is very much dependent on predictive biomarkers for patient selection. METHODS: We generated an in vitro model of acquired cetuximab resistance by chronically exposing three HNSCC cell lines to increasing cetuximab doses. Gene expression profiles of sensitive parental cells and resistant daughter cells were compared using microarray analysis. Growth inhibitory experiments were performed with an HB-EGF antibody and the MMP inhibitor, both in combination with cetuximab. Characteristics of EMT were analyzed using migration and invasion assays, immunofluorescent vimentin staining and qRT-PCR for several genes involved in this process. The function of the transcription factor AP-1 was investigated using qRT-PCR for several genes upregulated or downregulated in cetuximab resistant cells. Furthermore, anchorage independent growth was investigated using the soft agar assay. RESULTS: Gene expression profiling shows that cetuximab resistant cells upregulate several genes, including interleukin 8, the EGFR ligand HB-EGF and the metalloproteinase ADAM19. Cytotoxicity experiments with neutralizing HB-EGF antibody could not induce any growth inhibition, whereas an MMP inhibitor inhibited cell growth in cetuximab resistant cells. However, no synergetic effects combined with cetuximab could be observed. Cetuximab resistant cells showed traits of EMT, as witnessed by increased migratory potential, increased invasive potential, increased vimentine expression and increased expression of several genes involved in EMT. Furthermore, expression of upregulated genes could be repressed by the treatment with apigenin. The cetuximab resistant LICR-HN2 R10.3 cells tend to behave differently in cell culture, forming spheres. Therefore, soft agar assay was performed and showed more and larger colonies when challenged with cetuximab compared to PBS challenged cells. CONCLUSIONS: In summary, our results indicate that increased expression of the ligand HB-EGF could contribute to resistance towards cetuximab in our cetuximab resistant HNSCC cells. Furthermore, several genes upregulated or downregulated in cetuximab resistant cells are under control of the AP-1 transcription factor. However, more studies are warranted to further unravel the role of AP-1 in cetuximab resistance. PMID- 26269756 TI - High-resolution genomic profiling of thyroid lesions uncovers preferential copy number gains affecting mitochondrial biogenesis loci in the oncocytic variants. AB - Oncocytic change is the result of aberrant mitochondrial hyperplasia, which may occur in both neoplastic and non-neoplastic cells and is not infrequent in the thyroid. Despite being a well-characterized histologic phenotype, the molecular causes underlying such a distinctive cellular change are poorly understood. To identify potential genetic causes for the oncocytic phenotype in thyroid, we analyzed copy number alterations in a set of oncocytic (n=21) and non-oncocytic (n=20) thyroid lesions by high-resolution microarray-based comparative genomic hybridization (aCGH). Each group comprised lesions of diverse histologic types, including hyperplastic nodules, adenomas and carcinomas. Unsupervised hierarchical clustering of categorical aCGH data resulted in two distinct branches, one of which was significantly enriched for samples with the oncocytic phenotype, regardless of histologic type. Analysis of aCGH events showed that the oncocytic group harbored a significantly higher number of genes involved in copy number gains, when compared to that of conventional thyroid lesions. Functional annotation demonstrated an enrichment for copy number gains that affect genes encoding activators of mitochondrial biogenesis in oncocytic cases but not in their non-oncocytic counterparts. Taken together, our data suggest that genomic alterations may represent additional/alternative mechanisms underlying the development of the oncocytic phenotype in the thyroid. PMID- 26269757 TI - YES oncogenic activity is specified by its SH4 domain and regulates RAS/MAPK signaling in colon carcinoma cells. AB - Members of the SRC family of tyrosine kinases (SFK) display important functions in human cancer, but their specific role in tumorigenesis remains unclear. We previously demonstrated that YES regulates a unique oncogenic signaling important for colorectal cancer (CRC) progression that is not shared with SRC. Here, we addressed the underlying mechanism involved in this process. We show that YES oncogenic signaling relies on palmitoylation of its SH4 domain that controls YES localization in cholesterol-enriched membrane micro-domains. Specifically, deletion of the palmitoylation site compromised YES transforming activity, while addition of a palmitoylation site in the SH4 domain of SRC was sufficient for SRC to restore the transforming properties of cells in which YES had been silenced. Subsequently, SILAC phosphoproteomic analysis revealed that micro-domain associated cell adhesive components and receptor tyrosine kinases are major YES substrates. YES also phosphorylates upstream regulators of RAS/MAPK signaling, including EGFR, SHC and SHP2, which were not targeted by SRC due to the absence of palmitoylation. Accordingly, EGFR-induced MAPK activity was attenuated by YES down-regulation, while increased RAS activity significantly restored cell transformation that was lost upon YES silencing. Collectively, these results uncover a critical role for the SH4 domain in the specification of SFK oncogenic activity and a selective role for YES in the induction of RAS/MAPK signaling in CRC cells. PMID- 26269758 TI - RARRES3 suppressed metastasis through suppression of MTDH to regulate epithelial mesenchymal transition in colorectal cancer. AB - It has been reported that Retinoic acid receptor responder 3 (RARRES3) could suppress the metastasis of colorectal cancer (CRC). However, the underlying mechanism by which RARRES3 suppresses metastasis remains unknown. To investigate the functional involvement of RARRES3 in CRC, we first analyzed the expression of this protein between human CRC clinical samples and their corresponding normal controls and tested its correlation with clinicopathology as well as prognosis of CRC. We also examined the endogenous expression of RARRES3 by western-blot in a panel of CRC cell lines with different metastatic capacity. Cell proliferation, migration and invation of the CRC cell lines with either knockdown or reexpression of RARRES3 were examined by MTT, transwell and wound healing assays, respectively. The intrecellular signaling pathways affected by manipulations of RARRES3 in CRC cells were determined by western blot. Immunoprecipitation (IP) was employed to assess the interactionbetween proteins. To investigate the metastatic ability in vivo, CRC cell lines with manipulations of RARRES3 expression were inoculated in nude mice through tail vein injection. We confirmed that RARRES3 was significantly down-regulated in CRC tissues compared with normal controls. RARRES3 expression was not correlated with prognosis but significantly associated with CRC differentiation and lymphnodes metastases. We also found that RARRES3 was able to significantly suppress the metastasis of CRC cells both in vitro and in vivo through the regulation of epithelial-mesenchymal transition (EMT) process during which RARRES3 interactedwith MTDH in an opposite way. Taken together, we for the first time found that RARRES3 was able to suppress the metastasis of CRC both in vitro and in vivo via suppression of MTDH so as to regulate EMT. PMID- 26269759 TI - Twist1 is a potential prognostic marker for colorectal cancer and associated with chemoresistance. AB - Twist1 is a highly conserved basic helix-loophelix transcription factor, and has been shown to play an important role in carcinogenesis of many tumors including colorectal cancer (CRC). Here we aimed to investigate the role of Twist1 in the clinical significance and chemoresistance in CRC. In this study, we examined the correlation between Twist1 expression and clinicopathological characteristics using immunohistochemistry in patients with CRC. The molecular mechanisms of Twist1 expression and its effects on chemosensitivity to 5-Fluorouracil and oxaliplatin were also explored by MTT assay, colony forming assay, flow cytometry assay. The results indicate that Twist1 is overexpressed in cancer tissue, and its positive expression are related to histological grade (P=0.004), T-stage (P=0.033), N-stage (P=0.000), M-stage (P=0.040), TNM stage (P=0.002) and recurrence (P=0.023). Moreover, positive Twist1 expression is correlated with poor overall survival in CRC patients (P<0.0001), and is a significant independent prognostic indicator. In addition, we show that knockdown of Twist1 inhibits proliferation, and increased the percentage of apoptotic cells of CRC cell lines. Our findings suggest that Twist1 promotes proliferation and chemoresistance of CRC cells. Twist1 may be a potential prognostic marker and a molecular target for therapies. PMID- 26269760 TI - Cyclooxygenase-2 knockdown using retinoic acid chalcone (RAC), a promising therapeutic strategy for colon cancer. AB - Retinoic acid is an effective agent in the treatment of epithelial and hematological malignancies. The present study demonstrates that retinoic acid chalcone (RAC), an analogue of retinoic acid inhibits cell proliferation and induces apoptosis in HCT-15 and CT26.WT colon cancer cell lines. In HCT-15 cells the percentage of apoptotic cells increased from 32.4 +/- 3, 45.0 +/- 3 to 72.6 +/- 5% respectively at 10, 15 and 20 MUg/mL compared to 3.7% in control. Similarly in CT26.WT cells the percentage increased from 28.6 +/- 3, 41.2 +/- 3 to 65.4 +/- 5% on treatment with 10, 15 and 20 MUg/mL concentrations of RAC after 72 h compared to 2.9 +/- 1% in control. Western blotting, fluorescence-activated cell sorting analysis and reverse transcription-PCR assays were used to investigate these effects. RAC inhibited the overexpression of COX-2, PGE2 and PGE2 receptor (EP1 and EP4) in the colon cancer cell lines. RAC mediated inhibition of cell growth and induction of apoptosis through COX-2 inhibition was also confirmed by treating the HCT-15 and CT26.WT colon cancer cells with COX-2 inhibitor, indomethacin and transfection of cells with COX-2 small interfering RNA. In nude mice with tumor xenografts, treatment with RAC-supplemented diet caused inhibition of COX-2, PGE2, and PGE2 receptors (EP1, EP3, and EP4) in tumors. Thus RAC can be a potential candidate for the treatment of colon cancer through the inhibition of COX-2 expression and subsequent inhibition of PGE2 and PGE2 receptors. PMID- 26269761 TI - Overexpression of forkhead Box C2 promotes tumor metastasis and indicates poor prognosis in colon cancer via regulating epithelial-mesenchymal transition. AB - Forkhead box protein C2 (FOXC2) plays a vital role in carcinogenesis; however, its significance and prognostic value in colon cancer remain unclear. In this study, FOXC2 expression was analyzed in a tissue microarray (TMA) containing 185 samples of primary colon cancer tumor samples and in human colon cancer cell lines. The effect of FOXC2 on cell proliferation, tumorigenesis, and metastasis was examined in vitro and in vivo. FOXC2 was overexpressed in human colon cancer cells and tissues, and correlated with colon cancer progression and patient survival. Functional study demonstrated that FOXC2 promoted cell growth, cell migration, and tumor formation in nude mice, whereas knockdown of FOXC2 by short hairpin RNA (shRNAs) significantly suppressed cell growth, cell migration and tumor formation. Further study found that FOXC2 enhanced AKT activity with subsequent GSK-3beta phosphorylation and Snail stabilization, and then induced epithelial-mesenchymal transition (EMT) and promoted tumor invasion and metastasis. Collectively, FOXC2 promotes colon cancer metastasis by facilitating EMT and acts as a potential prognostic factor and therapeutic target in colon cancer. PMID- 26269762 TI - IFN-beta is a potent inhibitor of insulin and insulin like growth factor stimulated proliferation and migration in human pancreatic cancer cells. AB - INTRODUCTION: Pancreatic cancer is a highly aggressive malignancy with few treatment options. The overexpression of several growth factors, including insulin and insulin-like growth factors (IGFs), can underlie the aggressive nature of this disease. Previous research has demonstrated potent effects of interferon (IFN)-beta on pancreatic cancer cell growth, however up till now it is unknown whether IFN-beta is able to counteract IGF1, IGF2 and insulin-induced pancreatic cancer cell proliferation and migration. METHODS: Expression of IGF- and insulin receptors was determined and the stimulatory effects of IGF1, IGF2 and insulin on cell proliferation and migration, as well as the inhibitory effects of IFN-beta were evaluated in 3 human pancreatic adenocarcinoma cell lines. RESULTS: Both the insulin- and the IGF1 receptor were variably expressed in the cell lines. IGF1, IGF2 and insulin were capable of stimulating cell proliferation in all three cell lines, however cell migration was significantly enhanced only in the BxPC-3 cell line. IFN-beta significantly inhibited IGF1-, IGF2- and insulin-stimulated proliferation in all three cell lines in a dose and time dependent manner. Furthermore, in the BxPC-3 cell line IFN-beta significantly inhibited both basal and IGF1-, IGF2- and insulin-stimulated cell migration. CONCLUSION: Both IGF1, -2 and insulin were capable of stimulating proliferation and migration in human pancreatic cancer cells irrespective of the type of receptor expressed. This study demonstrates that insulin, in addition to IGF1 and IGF2, may play an important role in the progression of pancreatic cancer. Moreover, IFN-beta strongly inhibits growth factor stimulated cell proliferation and migration. Our study supports previous findings which have suggested that IFN-beta can be a potential promising anti-cancer agent in pancreatic cancer. PMID- 26269763 TI - GPX3 hypermethylation serves as an independent prognostic biomarker in non-M3 acute myeloid leukemia. AB - Hypermethylation of GPX3 (glutathione peroxidase 3) promoter has been identified in various solid tumors. However, the pattern of GPX3 promoter methylation in acute myeloid leukemia (AML) remains unknown. The current study was intended to investigate the clinical significance of GPX3 promoter methylation in de novo AML patients and further determine its role in regulating GPX3 expression. GPX3 promoter methylation status was detected in 181 de novo AML patients and 44 normal controls by real-time quantitative methylation-specific PCR and bisulfite sequencing PCR. Real-time quantitative PCR was carried out to assess GPX3 expression. GPX3 promoter was significantly methylated in AML patients compared with normal controls (P=0.022). The patients with GPX3 methylation presented significantly older age than those with GPX3 unmethylation (P=0.011). GPX3 methylated patients had significantly lower frequency of C/EBPA mutation and higher incidence of FLT3-ITD mutation (P=0.037 and 0.030, respectively). The non M3 patients with GPX3 methylation had significantly lower overall survival than those with GPX3 unmethylation (P=0.036). No significant correlation was observed between GPX3 expression and its promoter methylation (R=0.110, P=0.284). However, GPX3 mRNA level was significantly increased after 5-aza-2'-deoxycytidine treatment in leukemic cell line THP1. Our data suggest that GPX3 methylation predicts adverse clinical outcome in non-M3 AML patients. Moreover, GPX3 expression is regulated by its promoter methylation in leukemic cell line THP1. PMID- 26269764 TI - MicroRNA-143 acts as a tumor suppressor by targeting hexokinase 2 in human prostate cancer. AB - MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in cancer progression through regulating gene expression. Down-regulation of miR-143 has been reported in a number of cancers. However, the biological functions of miR 143 in prostate cancer remain largely unexplored. In this study, we showed that miR-143 expression was reduced in approximately 62.5% of the specimens examined. By loss-of-function and gain-of-function studies in human prostate cancer PC-3 cells, we demonstrated that miR-143 has an inhibitory effect on cell proliferation as evidenced by decreased cell viability, increased cell apoptosis and cell cycle arrest at the G1/S transition. Furthermore, we identified hexokinase 2 (HK2), a metabolic enzyme that executes the first step of aerobic glycolysis, as a target of miR-143 in prostate cancer. Knockdown of HK2 recapitulated the effects of miR-143 and accompanied with decreased glucose metabolism. Taken together, these data indicate that miR-143/HK2 axis plays an important role in the development of prostate cancer and represents a potential therapeutic target for prostate cancer. PMID- 26269765 TI - Tumor infiltrating lymphocytes (TILs) before and after neoadjuvant chemoradiotherapy and its clinical utility for rectal cancer. AB - BACKGROUNDS: Radiotherapy (RT) and chemotherapy (CT) can potentiate systemic antitumor immune effect. However, immunomodulation during RT or CT and their clinical implications in rectal cancer have not been thoroughly investigated. METHODS: We investigated alterations in the densities of tumor infiltrating lymphocytes (TILs) during chemoradiation and their clinical utilities in patients with rectal cancer. We analyzed 136 rectal cancer patients who underwent neoadjuvant RT, CT or chemoradiotherapy (CRT), followed by radical resection retrospectively. Pretreatment biopsy specimens and posttreatment resected specimens of all patients were immunostained for CD3 and CD8. The predictive value of TILs to neoadjuvant treatment and prognosis were examined. RESULTS: Densities of CD3+ and CD8+TILs in posttreatment specimens after RT, CT or CRT were all significantly higher than those in pretreatment specimens. There were no significant differences between each two of these three groups. High pretreatment CD3+ and CD8+TILs were associated with good response (TRG >= 3) after neoadjuvant treatments (P = 0.033 and 0.021). High CD3+TILs and CD8+TILs in pretreatment biopsy specimens were significantly associated with favorable disease free survival (DFS) (P = 0.010 and P = 0.022) and overall survival (OS) (P = 0.019 and P = 0.003). CONCLUSIONS: We may, thus, conclude that chemoradiation can enhance local immune response by increased TILs. High TILs densities before treatment are associated with good response to neoadjuvant chemoradiotherapy and a favorable prognosis. PMID- 26269766 TI - Significance of local treatment in patients with metastatic soft tissue sarcoma. AB - Metastatic soft tissue sarcomas (STS) represent enormous challenges to improve the low survival rate, which is almost the same as past 2 decades ago, although surgery, radiotherapy and radiofrequency ablation has been accepted in the treatment of metastatic STS. Moreover, STS varies between elderly and younger victims in the aspect of diagnoses, prognosis, and treatment strategies. In order to evaluate the role of local treatment in improving prognosis for patients with metastatic STS and select the proper candidates who will benefit from local therapy, a single-institution nearly 50-year experience were collected and reviewed. Finally, we found that local treatments could improve treatment response and survival, but overall survival advantage could not be seen in elderly patients. This conclusion from a single institution could serve as a basis for future prospective multi-institutional large-scale studies. PMID- 26269767 TI - Circulating levels of anti-angiogenic VEGF-A isoform (VEGF-Axxxb) in colorectal cancer patients predicts tumour VEGF-A ratios. AB - PURPOSE: Bevacizumab as an adjunct to chemotherapy improves survival for some patients with metastatic colorectal cancer. Immunohistochemical staining of samples from the registration ECOG E3200 trial of bevacizumab with FOLFOX demonstrated that only patients with carcinomas expressing low levels of VEGF A165b, an anti-angiogenic splice variant of the Vascular Endothelial Growth Factor family of proteins, benefited from bevacizumab treatment. To identify a more useful biomarker of response we tested the hypothesis that circulating VEGF A165b levels correlate with immunohistochemical staining. EXPERIMENTAL DESIGN: 17 patients with biopsy proven colorectal adenocarcinoma had pre-operative blood samples drawn. They underwent resection and had post-resection blood drawn. The plasma was analysed for levels of VEGF-Axxxb using enzyme-linked immunosorbent assay (ELISA) and the tumour blocks stained for VEGF-Axxxb and pan-VEGF-A. The normalised ratio of VEGF-Axxxb expression to that of panVEGF-A expression scored by IHC was calculated and correlated with plasma VEGF-A165b levels. RESULTS: Plasma levels of VEGF-Axxxb significantly correlated with the VEGF-Axxxb:panVEGF A ratio (r=0.594, P<0.02) in colorectal cancers. Median plasma VEGF-Axxxb levels were 151 pg/ml. The mean (1.5+/-0.17) and median, IQR (1.8, 1-2) IHC scores of the patients with greater than median plasma VEGF-Axxxb were significantly greater than those with less than median plasma VEGF-Axxxb levels (mean +/- SEM=0.85+/-10.12, median, IQR=1, 0.54-1). CONCLUSION: These results suggest that plasma VEGF-Axxxb levels could be an effective biomarker of response to Bevacizumab. These results indicate that a prospective trial is warranted to explore the use of plasma VEGF-Axxxb levels to stratify patients for colorectal cancer treatment by bevacizumab. PMID- 26269768 TI - Different patterns in the prognostic value of age for bladder cancer-specific survival depending on tumor stages. AB - To compare the pathological features and long-term survival of bladder cancer (BCa) in young patients with elderly counterparts. Using the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) population-based data, we identified 93115 patients with non-metastatic bladder cancer diagnosed between 1988 and 2003. Patients were categorized into young (50 years and under) and elderly groups (over 50 years of age). The overall and five-year bladder cancer specific survival (BCSS) data were obtained using Kaplan-Meier plots. Multivariable Cox regression models were built for the analysis of long-term survival outcomes and risk factors. There were significant differences between the two groups in primary site, pathologic grading, histologic type, AJCC stage (p<0.001). The overall and 5-year cancer specific survival rates were 88.1% and 90.8% in young group, 64.8% and 81.3% in elderly group, which had significant difference in both univariate and multivariate analysis (p<0.001). Further analysis showed this significant difference existed across all the AJCC stage patients. The study findings show different patterns in the prognostic value of age for determining BCSS, depending on the tumor stages. Compared with elderly patients, young patients with bladder cancer surgery appear to have unique characteristics and a higher overall and cancer specific survival rate. PMID- 26269769 TI - Endogenous Nodal promotes melanoma undergoing epithelial-mesenchymal transition via Snail and Slug in vitro and in vivo. AB - Nodal, an important embryonic morphogen, has been reported to modulate tumorigenesis. Epithelial-mesenchymal transition (EMT) plays an important role in cancer metastasis. We have previously reported that recombinant Nodal treatment can promote melanoma undergoing EMT, but the effects of endogenous Nodal on EMT are still unknown. Here we generated both Nodal-overexpression and -knockdown stable cell lines to investigate the in vitro and in vivo characteristics of Nodal-induced EMT in murine melanoma cells. Nodal-overexpression cells displayed increased migration ability, accompanied by typical phenotype changes of EMT. In contrast, Nodal-knockdown stable cells repressed the EMT phenotype as well as reduced cell motility. Results of animal experiments confirmed that overexpression of Nodal can promote the metastasis of melanoma tumor in vivo. Mechanistically, we found that Nodal-induced expression of Snail and Slug involves its activation of ALK/Smads and PI3k/AKT pathways, which is an important process in the Nodal-induced EMT. However, we also found that the EMT phenotype was not completely inhibited by blocking the paracrine activity of Nodal in Nodal overexpression cell line suggesting the presence of additional mechanism(s) in the Nodal-induced EMT. This study provides a better understanding of Nodal function in melanoma, and suggests targeting Nodal as a potential strategy for melanoma therapey. PMID- 26269770 TI - Review of running injuries of the foot and ankle: clinical presentation and SPECT CT imaging patterns. AB - Distance running is among the fastest growing sports, with record registration to marathons worldwide. It is estimated that more than half of recreational runners will experience injuries related to the practice of their sport. Three-phase bone scintigraphy is a very sensitive tool to identify sports injury, allowing imaging of hyperemia, stress reaction, enthesopathy and fractures, often before abnormalities can be detected on conventional anatomical modalities. In this article, we review the most common running related injuries and their imaging findings on bone scintigraphy with SPECT-CT. PMID- 26269772 TI - Biodistribution and pharmacokinetics of recombinant alpha1-microglobulin and its potential use in radioprotection of kidneys. AB - Peptide-receptor radionuclide therapy (PRRT) is a systemically administrated molecular targeted radiation therapy for treatment of neuroendocrine tumors. Fifteen years of clinical use show that renal toxicity, due to glomerular filtration of the peptides followed by local generation of highly reactive free radicals, is the main side-effect that limits the maximum activity that can be administrated for efficient therapy. alpha1-microglobulin (A1M) is an endogenous radical scavenger shown to prevent radiation-induced in vitro cell damage and protect non-irradiated surrounding cells. An important feature of A1M is that, following distribution to the blood, it is equilibrated to the extravascular compartments and filtrated in the kidneys. Aiming at developing renal protection against toxic side-effects of PRRT, we have characterized the pharmacokinetics and biodistribution of intravenously (i.v.) injected (125)I- and non-labelled recombinant human A1M and the (111)In- and fluorescence-labelled somatostatin analogue octreotide. Both molecules were predominantly localized to the kidneys, displaying a prevailing distribution in the cortex. A maximum of 76% of the injected A1M and 46% of the injected octreotide were present per gram kidney tissue at 10 to 20 minutes, respectively, after i.v. injection. Immunohistochemistry and fluorescence microscopy revealed a dominating co existence of the two substances in proximal tubules, with a cellular co localization in the epithelial cells. Importantly, analysis of kidney extracts displayed an intact, full-length A1M at least up to 60 minutes post-injection (p.i.). In summary, the results show a highly similar pharmacokinetics and biodistribution of A1M and octreotide, thus enabling the use of A1M to protect the kidneys tissue during PRRT. PMID- 26269771 TI - Imaging radiation response in tumor and normal tissue. AB - Although X-ray computed tomography (CT) and magnetic resonance imaging (MRI) are the primary imaging modalities used in the clinic to monitor tumor response to radiation therapy, multi-modal molecular imaging may facilitate improved early and specific evaluation of this process. Fast and accurate imaging that can provide both quantitative and biological information is necessary to monitor treatment and ultimately to develop individualized treatment options for patients. A combination of molecular and anatomic information will allow for deeper insight into the mechanisms of tumor response, which will lead to more effective radiation treatments as well as improved anti-cancer drugs. Much progress has been made in nuclear medicine imaging probes and MRI techniques to achieve increased accuracy and the evaluation of relevant biomarkers of radiation response. This review will emphasize promising molecular imaging techniques that monitor various biological processes following radiotherapy, including metabolism, hypoxia, cell proliferation, and angiogenesis. PMID- 26269773 TI - Measurement of hypoxia-related parameters in three sublines of a rat prostate carcinoma using dynamic (18)F-FMISO-Pet-Ct and quantitative histology. AB - Hypoxia is an important resistance factor in radiotherapy and measuring its spatial distribution in tumors non-invasively is therefore of major importance. This study characterizes the hypoxic conditions of three tumor sublines (AT1, HI and H) of the Dunning R3327 prostate tumor model, which differ in histology, differentiation degree, volume doubling time and androgenic sensitivity, using dynamic Fluoromisonidazole ((18)F-FMISO)-Positron Emission Tomography/Computed Tomography (PET-CT) and histology. Measurements were performed for two tumor volumes (average 0.8+/-0.5 cm(3) vs 4.4+/-2.8 cm(3)). Data were analyzed according to tumor subline as well as to the shape of the time activity curves (TACs), based on standardized uptake values (SUVs) and a two-tissue compartment model. Quantitative immunohistochemical studies of the hypoxic fraction, vessel density and vessel size were performed using pimonidazole, Hoechst 33342 and CD31 dyes. No significant FMISO uptake was found in small tumors, which had a mean SUV of 0.64+/-0.36, 0.55+/-0.10 and 0.45+/-0.08, for AT1, HI and H sublines respectively. In large tumors, the SUVs were 1.33+/-0.52, 1.12+/-0.83 and 0.63+/ 0.16 for AT1, HI and H sublines and the corresponding hypoxic fractions obtained with pimonidazole staining were 0.62+/-0.23, 0.54+/-0.24 and 0.07+/-0.10, respectively. The AT1- was the most and H-tumor was the least hypoxic for both methods (P<0.05). All measurements were able to discriminate different hypoxic conditions, however despite SUV and kinetic parameters correlated with the three identified TAC shapes, most of the histological results did not. These results demonstrate impact and limitations of static and dynamic PET-CT measurements to assess hypoxia non-invasively. PMID- 26269774 TI - OKN-007 decreases VEGFR-2 levels in a preclinical GL261 mouse glioma model. AB - Angiogenesis is essential to tumor progression, and the precise imaging of the angiogenic marker vascular endothelial growth factor receptor 2 (VEGFR-2) may provide an accurate evaluation for angiogenesis during a therapeutic response. With the use of molecular magnetic resonance imaging (mMRI), an in vitro cell assay indicated significantly decreased T1 relaxation values when tumor endothelial cells (TEC), which positively expressed VEGFR-2 (Western blot), were in the presence of the VEGFR-2 probe compared to TEC alone (P < 0.001). For in vivo mMRI evaluations, we assessed VEGFR-2 levels in untreated and OKN-007 treated GL261 mouse gliomas. Regarding treatment response, OKN-007 was also able to significantly decrease tumor volumes (P < 0.01) and increase survival (P < 0.001) in treated animals. Regarding in vivo detection of VEGFR-2, OKN-007 was found to significantly decrease the amount of VEGFR-2 probe (P < 0.05) compared to an untreated control group. Fluorescence imaging for the VEGFR-2 probe indicated that there was colocalization with the endothelial marker CD31 in an untreated tumor bearing mouse and decreased levels for an OKN-007-treated animal. Immuno-fluorescence imaging for VEGFR-2 indicated that OKN-007 treatment significantly decreased VEGFR-2 levels (P < 0.0001) when compared to untreated tumors. Immuno-electron microscopy was used with gold-labeled anti-biotin to detect the anti-VEGFR-2 probe within the plasma membrane of GL261 tumor endothelial cells. This is the first attempt at detecting in vivo levels of VEGFR 2 in a mouse GL261 glioma model and assessing the anti-angiogenic capability of an anticancer nitrone. The results indicate that OKN-007 treatment substantially decreased VEGFR-2 levels in a GL261 glioma model, and can be considered as an anti-angiogenic therapy in human gliomas. PMID- 26269775 TI - PET imaging of glioblastoma multiforme EGFR expression for therapeutic decision guidance. AB - After initial therapy and total resection of glioblastoma multiforme (GBM), 80 90% of recurrences occur at the surgical margins. Insufficient sensitivity and specificity of current imaging techniques based on non-specific vascular imaging agents lead to delay in diagnosis of residual and/or recurrent disease. A tumor specific imaging agent for GBM may improve detection of small residual disease in the post-operative period, and improve ability to distinguish tumor recurrence from its imaging mimics that can delay diagnosis. To this end, we developed an EGFR-targeted PET probe and assessed its ability to image EGFR WT (U87) and EGFRvIII (Gli36vIII) expressing GBMs in both murine intra-cranial xenografts and in a surgical-resection model. The developed imaging probe, (64)Cu-DOTAcetuximab F(ab')2, binds with a Kd of 11.2 nM to EGFR expressing GBM. (64)Cu-DOTA-cetuximab F(ab')2 specifically localized to intra-cranial tumor with a significant difference in SUVmean between tumor and contralateral brain for both Gli36vIII and U87 tumors (P<0.01 for both comparisons), with mean TBR of 22.5+/-0.7 for Gli36vIII tumors and 28.9+/-2.1 for U87 tumors (TBR+/-SEM). Tracer uptake by tumor was significantly inhibited by pre-injection with cetuximab (P<0.01 for both), with SUVmean reduced by 68% and 58% for Gli36vIII and U87 tumors, respectively. Surgical resection model PET-CT imaging demonstrates residual tumor and low nonspecific uptake in the resection site. We conclude that (64)Cu-DOTA cetuximab-F(ab')2 binds specifically to intracranial EGFR WT and EGFRvIII expressing GBM, demonstrates excellent TBR, and specifically images small residual tumor in a surgical model, suggesting future clinical utility in identifying true tumor recurrence. PMID- 26269776 TI - Optimization of the enhanced permeability and retention effect for near-infrared imaging of solid tumors with indocyanine green. AB - Surgery is the most effective method to cure patients with solid tumors. New techniques in near-infrared (NIR) cancer imaging are being used to identify surgical margins and residual tumor cells in the wound. Our goal was to determine the optimal time and dose for imaging solid tumors using Indocyanine Green. Syngeneic murine flank tumor models were used to test NIR imaging of ICG at various doses ranging from 0 to 10 mg/kg. Imaging was performed immediately after injection and up to 72 hours later. Biodistribution in the blood and murine organs were quantified by spectroscopy and fluorescence microscopy. Based on these results, a six patient dose titration study was performed. In murine flank tumors, the tumor-to-background ratio (TBR) for ICG at doses less than 5 mg/kg were less than 2 fold at all time points, and the surgeons could not subjectively identify tissue contrast. However, for doses ranging from 5 mg/kg to 10 mg/kg, the TBR ranged from 2.1 to 8.0. The tumor signal was best appreciated at 24 hours and the background was least pronounced after 24 hours. Biodistribution studies in the blood and murine organs revealed excretion through the biliary tree and gastrointestinal tract, with minimal blood fluorescence at the higher doses. A follow up pilot study confirmed that these findings were applicable to lung cancer patients, and tumor was clearly delineated from surrounding normal tissue by NIR imaging. For non-hepatic solid tumors, we found ICG was optimal when dosed at 5 mg/kg and 24 hours before surgery. PMID- 26269777 TI - Feasibility of (18)F-Fluorodeoxyglucose radiotracer dose reduction in simultaneous carotid PET/MR imaging. AB - The purpose of this study was to develop and validate low dose (18)F-FDG-PET acquisition protocols for detection of inflamed carotid plaques specifically for simultaneous PET/MR imaging. The hypothesis was that increasing the duration of the PET acquisition to match that of the MR acquisition might allow for the use of lower levels of the radiotracer, while preserving quantification and image quality. Seven subjects were scanned twice at least one week apart on a simultaneous PET/MR scanner using either the standard clinical dose of (18)F-FDG (373 +/- 63 MBq) for 8 minutes or a low dose (93 +/- 17 MBq) for 75 minutes. A maximum absolute percent difference of only 4.17% and 7.49% in the left and right carotid TBR was found between the standard dose and four time points of the low dose acquisitions (8, 24, 45, 75 minutes). Only the 8-minute low dose PET data was significantly different in terms of SNR (P = 0.009; % difference = -51%) and qualitative image quality evaluation (P = 0.0005; % difference = -45%). Our preliminary findings indicate that up to 75% reduction of the clinical standard (18)F-FDG dose could be achieved using the proposed acquisition scheme while maintaining accurate quantification and SNR. PMID- 26269778 TI - (18)F-FDG PET imaging in detection of radiation-induced vascular disease in lymphoma survivors. AB - Radiation therapy (RT) induces vascular changes that increase the risk of cardiovascular diseases in some patients. The objective was to determine if in vivo positron emission tomography (PET) with fluorodeoxyglucose ((18)F-FDG) can identify increased vascular inflammation in patients without changes in vascular intima media thickness (IMT). Patients previously receiving unilateral RT due to lymphoma were prospectively recruited (N=10). The untreated contralateral artery functioned as control. All patients underwent a dedicated vascular PET/CT. Vascular tracer uptake was quantified by drawing regions of interests around the carotid artery or the iliac arteries. The IMT of the carotid arteries was measured using ultrasound. Eight patients (25% male, 42-83 years old) that had received RT involving unilateral carotid arteries and 2 patients (both male, 38 and 58 years old) that had received radiotherapy involving the unilateral iliac artery were included. The patients had completed their RT 2-7 years before. Eight patients showed increased uptake of (18)F-FDG in the irradiated side compared to the non-irradiated side, 1 showed no difference, while 1 patient showed highest uptake in the non- irradiated side (P=0.04). Measurement of IMT showed that 4 patients had the highest thickness in the irradiated side, while the other 4 patients had the highest thickness in the non-irradiated side (P=0.8). In conclusion, we found that (18)F-FDG PET imaging may be used to detect vascular changes induced by RT. Larger prospective follow-up studies are needed to determine the prognostic value of increased vascular FDG-uptake. PMID- 26269779 TI - Effect of IKZF1 deletions on signal transduction pathways in Philadelphia chromosome negative pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL). AB - BACKGROUND: IKZF1 deletions are an unfavorable prognostic factor in children with Philadelphia chromosome positive (Ph(+)) as well as negative (Ph(-)) acute lymphoblastic leukemia (ALL). Although IKZF1 deletions occur in 10-15% of Ph(-) ALL cases, effects of IKZF1 deletions on signaling pathways in this group have not been extensively studied. Therefore, in this study we aimed to study the effect of IKZF1 deletions on active signal transduction pathways. METHODS: Multiplex ligation-dependent probe amplification (MLPA) was used to determine IKZF1 deletions and other copy number alterations in 109 pediatric B-Cell Precursor ALL (BCP-ALL) patients. Kinase activity profiling of 45 primary Ph(-) BCP-ALL patients (31 IKZF1 wild type patients and 14 patients harboring an IKZF1 alteration) and western blot analysis of 14 pediatric BCP-ALL samples was performed to determine active signal transduction pathways. RESULTS: Unsupervised hierarchical cluster analysis of kinome profiles of 45 pediatric Ph(-) ALL cases showed no clustering based on IKZF1 status. Comparing the phosphorylation intensities of peptides associated with signaling pathways known to be involved in BCP-ALL maintenance, we did not observe differences between the two groups. Western blot analysis of 14 pediatric BCP-ALL samples showed large variations in phosphorylation levels between the different ALL samples, independent of IKZF1 status. CONCLUSIONS: Based on these results we conclude that, although IKZF1 deletions appear to be an important clinical prognostic factor, we were unable to identify a unique IKZF1 dependent protein expression signature in pediatric Ph(-) ALL and consequently no specific targets for future therapy of Ph(-) IKZF1 deleted BCP-ALL could be identified. PMID- 26269780 TI - Danio rerio: Small Fish Making a Big Splash in Leukemia. AB - Zebrafish (Danio rerio) are widely used for developmental biology studies. In the past decade, D. rerio have become an important oncology model as well. Leukemia is one type of cancer where zebrafish are particularly valuable. As vertebrates, fish have great anatomic and biologic similarity to humans, including their hematopoietic and immune systems. As an experimental platform, D. rerio offer many advantages that mammalian models lack. These include their ease of genetic manipulation, capacity for imaging, and suitability for large-scale phenotypic and drug screens. In this review, we present examples of these strategies and others to illustrate how zebrafish have been and can be used to study leukemia. Besides appraising the techniques researchers apply and introducing the leukemia models they have created, we also highlight recent and exciting discoveries made using D. rerio with an eye to where the field is likely headed. PMID- 26269781 TI - Optimal beam sources for Stark decelerators in collision experiments: a tutorial review. AB - With the Stark deceleration technique, packets of molecules with a tunable velocity, a narrow velocity spread, and a high state purity can be produced. These tamed molecular beams find applications in high resolution spectroscopy, cold molecule trapping, and controlled scattering experiments. The quality and purity of the packets of molecules emerging from the decelerator critically depend on the specifications of the decelerator, but also on the characteristics of the molecular beam pulse with which the decelerator is loaded. We consider three frequently used molecular beam sources, and discuss their suitability for molecular beam deceleration experiments, in particular with the application in crossed beam scattering in mind. The performance of two valves in particular, the Nijmegen Pulsed Valve and the Jordan Valve, is illustrated by decelerating ND 3 molecules in a 2.6 meter-long Stark decelerator. We describe a protocol to characterize the valve, and to optimally load the pulse of molecules into the decelerator. We characterize the valves regarding opening time duration, optimal valve-to-skimmer distance, mean velocity, velocity spread, state purity, and relative intensity. PMID- 26269782 TI - Current Applications of Genetic Risk Scores to Cardiovascular Outcomes and Subclinical Phenotypes. AB - Genetic risk scores are a useful tool for examining the cumulative predictive ability of genetic variation on cardiovascular disease. Important considerations for creating genetic risk scores include the choice of genetic variants, weighting, and comparability across ethnicities. Genetic risk scores that use information from genome-wide meta-analyses can successfully predict cardiovascular outcomes and subclinical phenotypes, yet there is limited clinical utility of these scores beyond traditional cardiovascular risk factors in many populations. Novel uses of genetic risk scores include evaluating the genetic contribution of specific intermediate traits or risk factors to cardiovascular disease, risk prediction in high-risk populations, gene-by-environment interaction studies, and Mendelian randomization studies. Though questions remain about the ultimate clinical utility of the genetic risk score, further investigation in high-risk populations and new ways to combine genetic risk scores with traditional risk factors may prove to be fruitful. PMID- 26269783 TI - Diagnosing Autism in Individuals with Known Genetic Syndromes: Clinical Considerations and Implications for Intervention. AB - Assessing symptoms of autism in persons with known genetic syndromes associated with intellectual and/or developmental disability is a complex clinical endeavor. We suggest that a developmental approach to evaluation is essential to reliably teasing apart global impairments from autism-specific symptomology. In this chapter, we discuss our assumptions about autism spectrum disorders, the process of conducting a family-focused, comprehensive evaluation with behaviorally complex children and some implications for intervention in persons with co occurring autism and known genetic syndromes. PMID- 26269785 TI - A qualitative inquiry into the challenges and complexities of research supervision: viewpoints of postgraduate students and faculty members. AB - INTRODUCTION: The supervision of academic theses at the Universities of Medical Sciences is one of the most important issues with several challenges. The aim of the present study is to discover the nature of problems and challenges of thesis supervision in Iranian universities of medical sciences. METHODS: The study was conducted with a qualitative method using conventional content analysis approach. Nineteen faculty members, using purposive sampling, and 11 postgraduate medical sciences students (Ph.D students and residents) were selected on the basis of theoretical sampling. The data were gathered through semi-structured interviews and field observations in Shiraz and Isfahan universities of medical sciences from September 2012 to December 2014. The qualitative content analysis was used with a conventional approach to analyze the data. RESULTS: While experiencing the nature of research supervision process, faculties and the students faced some complexities and challenges in the research supervision process. The obtained codes were categorized under 4 themes Based on the characteristics; included "contextual problem", "role ambiguity in thesis supervision", "poor reflection in supervision" and "ethical problems". CONCLUSION: The result of this study revealed that there is a need for more attention to planning and defining the supervisory, and research supervision. Also, improvement of the quality of supervisor and students relationship must be considered behind the research context improvement in research supervisory area. PMID- 26269786 TI - A study of the professional development needs of Shiraz high schools' principals in the area of educational leadership. AB - INTRODUCTION: The increased emphasis on standards-based school accountability since the passage of the no child left behind act of 2001 is focusing critical attention on the professional development of school principals and their ability to meet the challenges of improving the student outcomes. Due to this subject, the current study examined professional development needs of Shiraz high schools principals. METHODS: The statistical population consisted of 343 principals of Shiraz high schools, of whom 250 subjects were selected using Krejcie and Morgan (1978) sample size determination table. To collect the data, a questionnaire developed by Salazar (2007) was administered. This questionnaire was designed for professional development in the leadership skills/competencies and consisted of 25 items in each leadership performance domain using five-point Likert-type scales. The content validity of the questionnaire was confirmed and the Cronbach's Alpha coefficient was (a=0.78). To analyze the data, descriptive statistics and Paired-Samples t-test were used. Also, the data was analyzed through SPSS14 software. RESULTS: The findings showed that principals' "Importance" ratings were always higher than their "Actual proficiency" ratings. The mean score of the difference between "Importance" and "Actual proficiency" pair on "Organizing resources" was 2.11, making it the highest "need" area. The lowest need area was "Managing the organization and operational procedures" at 0.81. Also, the results showed that there was a statistically significant difference between the means of the "Importance" and the corresponding means on the "Actual proficiency" (Difference of means=1.48, t=49.38, p<0.001). CONCLUSION: Based on the obtained results, the most important professional development needs of the principals included organizing resources, resolving complex problems, understanding student development and learning, developing the vision and the mission, building team commitment, understanding measurements, evaluation and assessment strategies, facilitating the change process, solving problems and making decisions. In other words, the principals had statistically significant professional development needs in all areas of the educational leadership. Also, the results suggested that today's school principals need to grow and learn throughout their careers by ongoing professional development. PMID- 26269784 TI - The Role of Translational Regulation in Survival after Radiation Damage; an Opportunity for Proteomics Analysis. AB - In this review, we will summarize the data from different model systems that illustrate the need for proteome-wide analyses of the biological consequences of ionizing radiation (IR). IR remains one of three main therapy choices for oncology, the others being surgery and chemotherapy. Understanding how cells and tissues respond to IR is essential for improving therapeutic regimes against cancer. Numerous studies demonstrating the changes in the transcriptome following exposure to IR, in diverse systems, can be found in the scientific literature. However, the limitation of our knowledge is illustrated by the fact that the number of transcripts that change after IR exposure is approximately an order of magnitude lower than the number of transcripts that re-localize to or from ribosomes under similar conditions. Furthermore, changes in the post translational modifications of proteins (phosphorylation, acetylation as well as degradation) are profoundly important for the cellular response to IR. These considerations make proteomics a highly suitable tool for mechanistic studies of the effect of IR. Strikingly such studies remain outnumbered by those utilizing proteomics for diagnostic purposes such as the identification of biomarkers for the outcome of radiation therapy. Here we will discuss the role of the ribosome and translational regulation in the survival and preservation of cells and tissues after exposure to ionizing radiation. In doing so we hope to provide a strong incentive for the study of proteome-wide changes following IR exposure. PMID- 26269787 TI - Designing and conducting MD/MPH dual degree program in the Medical School of Shiraz University of Medical Sciences. AB - INTRODUCTION: Many studies have focused on the need of health systems to educated physicians in the clinical prevention, research methodology, epidemiology and health care management and emphasize the important role of this training in the public health promotion. On this basis, Shiraz University of Medical Sciences (SUMS) has established MD/MPH dual degree program since the year 2012. METHODS: In the current study, Delphi technique was used. Both qualitative and quantitative methods were applied in the Delphi process. The Delphi team members including experts with extensive experience in teaching, research and administration in the field of educational management and health/medical education reached consensus in almost 86% of the questionnaire items through three Delphi rounds. MD/MPH program for SUMS was designed based on the items agreed and thematic analysis used in these rounds. RESULTS: The goals, values, mission and program requirements including the period, the entrance condition, and the number of units, and certification were determined. Accordingly, the courses of the program are presented in parallel with the MD education period. MPH courses consist of 35 units including 16 obligatory and 15 voluntary ones. CONCLUSION: Designing MD/MPH program in SUMS based on the existent models in the universities in different countries, compatible with educational program of this university and needs of national health system in Iran, can be a beneficial measure towards promoting the students' knowledge and theoretical/practical skills in both individual and social level. Performing some additional research to assess the MD/MPH program and some cohort studies to evaluate the effect of this program on the students' future professional life is recommended. PMID- 26269788 TI - Shiraz medical students' perceptions of their colleagues' professional behavior. AB - INTRODUCTION: Today, development of professionalism is a critical aim of medical schools. Studies have demonstrated that medical students' perceived level of professionalism is inadequate worldwide. This study aimed to investigate the medical students' perceptions of their colleagues' professional behavior. METHODS: This study is a cross-sectional study with 280 medical students at Shiraz University of Medical Sciences in their fifth to seventh year of study as the sample. The study was performed during one month in 2013, using stratified random sampling method. The instrument of the study was the Persian version of the questionnaire of the American Board of Internal Medicine (ABIM).The questionnaire includes demographic information, questions about the meaning of the professionalism, history of medical ethics education programs and 12 behavioral questions. The data were analyzed using student t-test and Pearson correlation test. The significance level was set as 0.05. RESULTS: Forty percent of respondents did not know the meaning of professionalism. The mean+/-SD score of behavioral questions was 5.91+/-1.2 on a scale from 0 to 10. The mean+/-SD score of excellence questions was 4.94+/-1.7. It was 7.05+/-1.9 for 'honor/integrity', and 6.07+/-2.1 for 'altruism/respect' questions. There was a significant association between gender and excellence score (p=0.007). CONCLUSION: Medical students assessed their colleagues' professional behavior as poor. They did not have proper information about professionalism. Medical students are future general practitioners and respecting medical ethics by them is very important in a perfect health system. Universities should emphasize the importance of teaching professionalism to medical students and faculty members, using innovative education methods. PMID- 26269790 TI - A survey of the effective factors in students' adherence to university dress code policy, using the theory of reasoned action. AB - INTRODUCTION: Recognizing the determinants of behavior plays a major role in identification and application of effective strategies for encouraging individuals to follow the intended pattern of behavior. The present study aimed to analyze the university students' behaviors regarding the amenability to dress code, using the theory of reasoned action (TRA). METHODS: In this cross sectional study, 472 students were selected through multi-stage random sampling. The data were collected using a researcher-made questionnaire whose validity was confirmed by specialists. Besides, its reliability was confirmed by conducting a pilot study revealing Cronbach's alpha coefficients of 0.93 for attitude, 0.83 for subjective norms, 0.94 for behavioral intention and 0.77 for behavior. The data were entered into the SPSS statistical software and analyzed using descriptive and inferential statistics (Mann-Whitney, correlation and regression analysis). RESULTS: Based on the students' self-reports, conformity of clothes to the university's dress code was below the expected level in 28.87% of the female students and 28.55% of the male ones. The mean scores of attitude, subjective norms, and behavioral intention to comply with dress code policy were 28.78+/ 10.08, 28.51+/-8.25 and 11.12+/-3.84, respectively. The students of different colleges were different from each other concerning TRA constructs. Yet, subjective norms played a more critical role in explaining the variance of dress code behavior among the students. CONCLUSION: Theory of reasoned action explained the students' dress code behaviors relatively well. The study results suggest paying attention to appropriate approaches in educational, cultural activities, including promotion of student-teacher communication. PMID- 26269789 TI - The main indicators for Iranian hospital ethical accreditation. AB - INTRODUCTION: The application of organizational ethics in hospitals is one of the novel ways to improve medical ethics. Nowadays achieving efficient and sufficient ethical hospital indicators seems to be inevitable. In this connection, the present study aims to determine the best indicators in hospital accreditation. METHODS: 69 indicators in 11 fields to evaluate hospital ethics were achieved through a five-step qualitative and quantitative study including literature review, expert focus group, Likert scale survey, 3 rounded Delphi, and content validity measurement. Expert focus group meeting was conducted, employing Nominal Group Technique (NGT). After running NGT, a three rounded Delphi and parallel to Delphi and a Likert scale survey were performed to obtain objective indicators for each domain. The experts were all healthcare professionals who were also medical ethics researchers, teachers, or PhD students. Content validity measurements were computed, using the viewpoints of two different expert groups, some ethicists, and some health care professionals (n=46). RESULTS: After conducting NGT, Delphi, Likert survey, 11 main domains were listed including: Informed consent, Medical confidentiality, Physician-patient economic relations, Ethics consultation policy in the hospital, Ethical charter of hospital, Breaking bad medical news protocol, Respect for the patients' rights, Clinical ethics committee, Spiritual and palliative care unit programs in the hospitals, Healthcare professionals' communication skills, and Equitable access to the healthcare. Also 71 objective indicators for these 11 domains were listed in 11 tables with 5 to 8 indicators per table. Content Validity Ratio (CVR) measurements were done and 69 indicators were highlighted. CONCLUSION: The domains listed in this study seem to be the most important ones for evaluating hospital ethics programs and services. Healthcare organizations' accreditation and ranking are crucial for the improvement of healthcare services. Ethics programs would also motivate hospitals to improve their services and move towards patients' satisfaction. In this regard, more involvement of bioethicists can help healthcare organizations to develop ethics programs and ensure ethics-based practice in hospitals. PMID- 26269791 TI - Qualitative Evaluation of General Practitioner Training Program as Viewed by Graduates from Shiraz, Fasa and Jahrom Medical Universities. AB - INTRODUCTION: The majority of countries have brought the quality of higher education into focus in the past few years. They have tried to improve the quality of their own higher education. The studies show that Iranian Universities are not at an accepted level in terms of quality. They have encountered several problems which have diminished their quality level. This study aimed at assessing the quality of medical education program as viewed by general practitioners graduated from Shiraz, Fasa and Jahrom Medical Universities. METHODS: This is a cross-sectional study. 215 subjects were selected based on a census of all the general practitioners graduated from Shiraz, Fasa and Jahrom Universities during 2011-2013. The questionnaire used for collecting the data was that of the Association of Graduates from American Medical Colleges. The collected data were then analyzed using SPSS 14 through which such descriptive and bivariate statistics as percentage, means, Standard Deviation and ANOVA were used. The level of significance was set to 0.05. RESULTS: The questionnaire return rate was 97%. As to the graduates' preclinical experiences, five indices were studied which were assessed as "average" in graduates' views. However, with respect to their clinical experiences five indices were equally studied, among which such indices as "Communication skills" and "The quality of medical apprenticeship" were evaluated as "desirable" in view of the graduates from the very three universities. On the contrary, the quality of clinical experiences and technological skills was evaluated as "almost weak"; furthermore, the integration of basic science with required clinical experience was also considered "weak". CONCLUSION: It seems essential to set up an annual assessment of general practitioner education program and a review of the medical education program in Iran based on the global medical advancement and international standards. PMID- 26269792 TI - Developing comprehensive course evaluation guidelines in Tehran University of Medical Sciences. PMID- 26269793 TI - The human urothelial tight junction: claudin 3 and the ZO-1alpha+ switch. AB - OBJECTIVE: Tight junctions are multicomponent structures, with claudin proteins defining paracellular permeability. Claudin 3 is a candidate for the exceptional "tightness" of human urothelium, being localised to the terminal tight junction (TJ) of superficial cells. Our aim was to determine whether claudin 3 plays an instigating and/or a functional role in the urothelial TJ. MATERIALS AND METHODS: Normal human urothelial (NHU) cells maintained as non-immortalised cell lines were retrovirally-transduced to over-express or silence claudin 3 expression. Stable sublines induced to stratify or differentiate were assessed for TJ formation by immunocytochemistry and transepithelial electrical resistance (TER). Expression of claudin 3, ZO-1 and ZO-1alpha+ was examined in native urothelium by immunohistochemistry. RESULTS: Claudin 3 expression was associated with differentiation and development of a tight barrier and along with ZO-1 and ZO 1alpha+ was localised to the apical tight junction in native urothelium. Knockdown of claudin 3 inhibited formation of a tight barrier in three independent cell lines, however, overexpression of claudin 3 was not sufficient to induce tight barrier development in the absence of differentiation. A differentiation-dependent induction of the ZO-1alpha+ isoform was found to coincide with barrier formation. Whereas claudin 3 overexpression did not induce the switch to co-expression of ZO-1alpha-/ZO-1alpha+, claudin 3 knockdown decreased localisation of ZO-1 to the TJ and resulted in compromised barrier function. CONCLUSIONS: Urothelial cytodifferentiation is accompanied by induction of claudin 3 which is essential for the development of a terminal TJ. A coordinated switch to the ZO-1alpha+ isotype was also observed and for the first time may indicate that ZO-1alpha+ is involved in the structural assembly and function of the urothelial terminal TJ. PMID- 26269794 TI - Epidemiologic Investigation of a Cluster of Neuroinvasive Bacillus cereus Infections in 5 Patients With Acute Myelogenous Leukemia. AB - Background. Five neuroinvasive Bacillus cereus infections (4 fatal) occurred in hospitalized patients with acute myelogenous leukemia (AML) during a 9-month period, prompting an investigation by infection control and public health officials. Methods. Medical records of case-patients were reviewed and a matched case-control study was performed. Infection control practices were observed. Multiple environmental, food, and medication samples common to AML patients were cultured. Multilocus sequence typing was performed for case and environmental B cereus isolates. Results. All 5 case-patients received chemotherapy and had early-onset neutropenic fevers that resolved with empiric antibiotics. Fever recurred at a median of 17 days (range, 9-20) with headaches and abrupt neurological deterioration. Case-patients had B cereus identified in central nervous system (CNS) samples by (1) polymerase chain reaction or culture or (2) bacilli seen on CNS pathology stains with high-grade B cereus bacteremia. Two case-patients also had colonic ulcers with abundant bacilli on autopsy. No infection control breaches were observed. On case-control analysis, bananas were the only significant exposure shared by all 5 case-patients (odds ratio, 9.3; P = .04). Five environmental or food isolates tested positive for B cereus, including a homogenized banana peel isolate and the shelf of a kitchen cart where bananas were stored. Multilocus sequence typing confirmed that all case and environmental strains were genetically distinct. Multilocus sequence typing-based phylogenetic analysis revealed that the organisms clustered in 2 separate clades. Conclusions. The investigation of this neuroinvasive B cereus cluster did not identify a single point source but was suggestive of a possible dietary exposure. Our experience underscores the potential virulence of B cereus in immunocompromised hosts. PMID- 26269795 TI - Comparison of Rapid Point-of-Care Tests for Detection of Antibodies to Hepatitis C Virus. AB - Background. Hepatitis C is one of the most prevalent blood-borne diseases in the United States. Despite the benefits of early screening, among 3.2 million Americans who are infected with hepatitis C virus (HCV), 50%-70% are unaware of their infection status. Methods. Data were collected between 2011 and 2014, from 1048 clients who were in the following groups: (1) injection drug users, (2) women at sexual risk, (3) gay and bisexual men, and (4) transgender individuals. The sensitivity and specificity of point-of-care tests included (1) the MedMira rapid human immunodeficiency virus (HIV)/HCV antibody test, (2) MedMira hepatitis B (HBV)/HIV/HCV antibody test, (3) Chembio HCV Screen Assay used with both whole blood and (4) oral specimens, (5) Chembio HIV-HCV Assay also used with both whole blood and (6) oral specimens, (7) Chembio HIV-HCV-Syphilis Assay, and (8) OraSure HCV Rapid Antibody Test used with whole blood. The gold standard for the HCV tests were HCV enzyme immunoassay (EIA) 2.0. Results. OraSure had the highest sensitivity at 92.7% (95% confidence interval [CI] = 88.8%-96.5%) followed closely by Chembio's 3 blood tests at 92.1% (95% CI = 87.7%-96.4%), 91.5% (95% CI = 87.2%-95.7%), and 92.3% (95% CI = 88.4%-96.2%). The sensitivities of MedMira HIV/HCV and MedMira HIV/HCV/HBV tests were the lowest, at 79.1% (95% CI = 72.6% 85.5%), and 81.5% (95% CI = 75.2%-87.8%), respectively. Specificity for the OraSure was 99.8% (95% CI = 99.4%-100%); specificity for the Chembio blood tests was 99.2% (95% CI = 98.6%-99.9%), 99.4% (95% CI = 98.8%-99.9%), and 99.3% (95% CI = 98.8%-99.9%); and specificity for the MedMira was100% and 100%. False-negative results were associated with HIV and hepatitis B core antibody serostatus. Conclusions. The OraSure and Chembio blood tests (including those multiplexed with HIV and syphilis) appear to good performance characteristics. This study has identified potential limitations of rapid testing in those testing positive for HIV and HBcAb. There should be discussion of updates to the 2013 CDC guidance. PMID- 26269796 TI - Cluster of Leptospirosis Acquired Through River Surfing in Switzerland. AB - Background. In Switzerland, leptospirosis is still considered as a travel associated disease. After the surprising diagnosis of leptospirosis in a patient who was initially suspected as having primary human immunodeficiency virus infection, we recognized that acquisition of leptospirosis occurred through recreational activities and we identified additional affected individuals. Methods. Detailed anamnesis, excluding occupational exposure, acquisition abroad, and pet contacts, enabled us to detect the source of infection and identify a cluster of leptospirosis. Convalescent sera testing was performed to confirm Leptospira infection. Microscopic agglutination tests were used to determine the infecting serovar. Results. We identified a cluster of leptospirosis in young, previously healthy persons. Acquisition of leptospirosis was traced back to a surfing spot on a river in Switzerland (Reuss, Aargau). Clinical presentation was indistinct. Two of the 3 reported cases required hospitalization, and 1 case even suffered from meningitis. Serologic tests indicated infection with the serovar Grippotyphosa in all cases. With the exception of the case with meningitis, no antibiotics were administered, because leptospirosis was diagnosed after spontaneous resolution of most symptoms. Despite a prolonged period of convalescence in 2 cases, full recovery was achieved. Recent reports on beavers suffering from leptospirosis in this region underline the possible water-borne infection of the 3 cases and raise the question of potential wildlife reservoirs. Conclusions. Insufficient awareness of caregivers, which may be promoted by the missing obligation to report human leptospirosis, combined with the multifaceted presentation of the disease result in significant underdiagnosis. More frequent consideration of leptospirosis as differential diagnosis is inevitable, particularly as veterinary data suggest re emergence of the disease. PMID- 26269797 TI - Symptoms of Autonomic Dysfunction in Human Immunodeficiency Virus. AB - This retrospective study evaluated the frequencies of symptoms associated with autonomic dysfunction in human immunodeficiency virus (HIV)-infected patients on stable combined antiretroviral therapy. Patients infected with HIV reported higher frequencies of dysautonomia symptoms compared with HIV-negative patients, particularly in the autonomic domains related to urinary, sleep, gastroparesis, secretomotor, pupillomotor, and male sexual dysfunction. PMID- 26269798 TI - Conditionally replicating adenovirus prevents pluripotent stem cell-derived teratoma by specifically eliminating undifferentiated cells. AB - Incomplete abolition of tumorigenicity creates potential safety concerns in clinical trials of regenerative medicine based on human pluripotent stem cells (hPSCs). Here, we demonstrate that conditionally replicating adenoviruses that specifically target cancers using multiple factors (m-CRAs), originally developed as anticancer drugs, may also be useful as novel antitumorigenic agents in hPSC based therapy. The survivin promoter was more active in undifferentiated hPSCs than the telomerase reverse transcriptase (TERT) promoter, whereas both promoters were minimally active in differentiated normal cells. Accordingly, survivin responsive m-CRA (Surv.m-CRA) killed undifferentiated hPSCs more efficiently than TERT-responsive m-CRAs (Tert.m-CRA); both m-CRAs exhibited efficient viral replication and cytotoxicity in undifferentiated hPSCs, but not in cocultured differentiated normal cells. Pre-infection of hPSCs with Surv.m-CRA or Tert.m-CRA abolished in vivo teratoma formation in a dose-dependent manner following hPSC implantation into mice. Thus, m-CRAs, and in particular Surv.m-CRAs, represent novel antitumorigenic agents that could facilitate safe clinical applications of hPSC-based regenerative medicine. PMID- 26269800 TI - Chest X-ray quiz. PMID- 26269799 TI - Replicating Nucleosomes. AB - Eukaryotic replication disrupts each nucleosome as the fork passes, followed by re-assembly of disrupted nucleosomes and incorporation of newly synthesized histones into nucleosomes in the daughter genomes. In this review, we examine this process of replication-coupled nucleosome assembly to understand how characteristic steady state nucleosome landscapes are attained. Recent studies have begun to elucidate mechanisms involved in histone transfer during replication and maturation of the nucleosome landscape after disruption by replication. A fuller understanding of replication-coupled nucleosome assembly will be needed to explain how epigenetic information is replicated at every cell division. PMID- 26269801 TI - Plasma-assisted synthesis and pressure-induced structural transition of single crystalline SnSe nanosheets. AB - Two-dimensional tin selenide (SnSe) nanosheets were synthesized using a plasma assisted direct current arc discharge method. The structural characterization indicates that the nanosheets are single-crystalline with an average thickness of ~25 nm and a lateral dimension of 500 nm. The high pressure behaviors of the as synthesized SnSe nanosheets were investigated by in situ high-pressure synchrotron angle-dispersive X-ray diffraction and Raman scattering up to ~30 GPa in diamond anvil cells at room temperature. A second-order isostructural continuous phase transition (Pnma -> Cmcm) was observed at ~7 GPa, which is considerably lower than the transition pressure of bulk SnSe. The reduction of transition pressure is induced by the volumetric expansion with softening of the Poisson ratio and shear modulus. Moreover, the measured zero-pressure bulk modulus of the SnSe nanosheets coincides with bulk SnSe. This abnormal phenomenon is attributed to the unique intrinsic geometry in the nanosheets. The high pressure bulk modulus is considerably higher than the theoretical value. The pressure-induced morphology change should be responsible for the improved bulk modulus. PMID- 26269802 TI - Cochrane review finds little evidence for cardioprotection from HRT, though some support for the "timing hypothesis". PMID- 26269803 TI - Oophorectomy benefits in breast cancer patients with BRCA1 mutation. PMID- 26269804 TI - Incidence of falls among older women in Finland unaffected by vitamin D or exercise. PMID- 26269805 TI - Highlights from the Society of Gynecologic Oncology 2015 Annual Meeting on Women's Cancer. PMID- 26269806 TI - Summary of the 2015 American Association for Cancer Research (AACR) Annual Meeting. PMID- 26269807 TI - In Memoriam: John O. Corliss (1922 - 2014). PMID- 26269808 TI - Evidence-based practice beliefs and behaviors of nurses providing cancer pain management. PMID- 26269809 TI - Dr Guido Pieles, a paediatric cardiology lecturer, discusses research to identify the effects of exercise on young hearts with Mark Nicholls. PMID- 26269810 TI - [Ask before classify as "allergic to penicillin"]. PMID- 26269811 TI - [Increase of infective endocarditis incidence: Is the discontinuation of prophylaxis in England to blame?]. PMID- 26269812 TI - In memoriam: Jean-Pierre Grignet. PMID- 26269813 TI - Breaking News: Update on Two-Midnight Rule. RACS have new limits; doctors more leeway. PMID- 26269814 TI - Root cause analysis is not enough. Add action to your analysis. PMID- 26269815 TI - Are you worrying about med rec? The issue is still a problem, says ECRI. PMID- 26269816 TI - CMS certifies registry as a Qualified Clinical Data Registry. FORCE members can get dual use from data. PMID- 26269817 TI - GI QI success expands to other specialties. Quality gains show promise in new units. PMID- 26269818 TI - Nepticulidae (Lepidoptera) of East Asia (1). Re-examination of the male genitalia of types deposited at the Russian Academy of Sciences . AB - East Asia is famous for its tremendous overall biodiversity, and the Nepticulidae are no exception. The majority of the currently known fauna of Nepticulidae was described in 1984-1987 by several authors, but R. Puplesis is the author of the largest number of new species from the region. Unfortunately, the genitalia of all species from Primorskiy Kray, Sakhalin, and the Kuril Islands were described from temporary slides in glycerol, and therefore, the drawings do not always show all details of genital armature or may be confusing. Without the baseline data providing morphology of genital armature of type material, it is impossible to continue studies on the East Asiatic fauna of Nepticulidae. In this paper we reexamine and document for the first time with photographs the types of 56 species described by R. Puplesis from the Russian Far East. Details of the morphology is updated for most of the re-examined species. PMID- 26269819 TI - Berengeria Gil-Santana & Coletto-Silva, a junior synonym of Ectrichodiella Fracker & Bruner, with new records and taxonomic notes on Ectrichodiinae from Brazil, and with keys to Ectrichodiinae and Reduviinae genera of the New World (Hemiptera: Heteroptera: Reduviidae). AB - Berengeria Gil-Santana & Coletto-Silva, 2005 is considered a junior synonym of Ectrichodiella Fracker & Bruner, 1924. Ectrichodiella minima (Valdes, 1910) and E. rafaeli (Gil-Santana & Coletto-Silva, 2005), new. comb. are redescribed. Taxonomic notes on Brontostoma alboannulatum (Stal, 1860), B. discus (Burmeister, 1835), B. nanus Carpintero, 1980, B. rubrovenosum (Stal, 1860), and B. trux (Stal, 1859) are given. Brontostoma diringshofeni Gil-Santana & Baena, 2009, B. nanus, and Racelda robusta Berenger & Gil-Santana, 2005 are recorded from Brazil for the first time. Keys to Ectrichodiinae and Reduviinae genera of the New World are presented. PMID- 26269820 TI - Nepticulidae (Lepidoptera) of East Asia (2). Study of a collection sample deposited at the Russian Academy of Sciences, with descriptions of new species and a checklist. AB - Over the few couple of decades, the Nepticulidae of East Asia have been the subject of continuing investigation. Male genitalia of the nepticulid species described from Primorskiy Kray (the Russian Far East) were re-examined in the preceding paper in this journal. The present paper continues our study on the diversity and systematics of the Nepticulidae of East Asia based on a sample of specimens collected in 1974-1990 at various sites of the southern part of Primorskiy Kray and treats 35 species: two new taxa (Ectoedemia ortiva sp. nov. and E. species 219) and 33 other species. Seventeen of them are briefly discussed and illustrated with photographs of male genitalia. Two new synonyms are proposed, and three new distribution records are provided. We also provide an updated checklist of the Nepticulidae of East Asia, which comprises 105 species; 67 species occur in the Russian Far East and 53 in Japan (20 of which occur both in Japan and Russia). Species with Euro-East Asiatic distribution currently comprise 11% of the Japanese fauna and 16% of the continental fauna of the Russian Far East, Primorskiy Kray. PMID- 26269821 TI - Phylogenetic relationships of Culex (Culex) species (Diptera, Culicidae) from Argentina based on morphological characters. AB - The purpose of this study was for the first time to establish phylogenetic hypotheses among Culex (Culex) species from Argentina, and to evaluate the relationships of this subgenus with subgenera Phenacomyia and Phytotelmatomyia. We employed maximum parsimony to analyse morphological characters derived from the morphology of the adult, pupal and larval stages. More than 30 figures, including photographs, illustrating 87 characters are provided. The cladistic analysis of 61 terminal taxa and 95 characters was undertaken, under implied weighting method, with a range of K values from 6 to 9. Three unstable taxa were detected therefore a reduced strict consensus tree was created. The subgenus Culex appears polyphyletic relative to subgenus Oculeomyia. The internal classification of subgenus Culex is shown to be chaotic; the Pipiens Group is polyphyletic relative to the Sitiens and Coronator Groups, the latter being polyphyletic with respect to the Pipiens Group. Phylogenetic analysis combining characters provided by morphology and molecular sources are needed to interpret more fully the relationships in the group. PMID- 26269822 TI - Three new species of Neozygina Dietrich & Dmitriev (Hemiptera, Cicadellidae, Typhlocybinae) from Argentina, with a key to South American species. AB - Three new species of Neozygina Dietrich & Dmitriev are described from Argentina, N. apicalis sp. nov., N. bifurcata sp. nov. and N. spinula sp. nov. Detailed morphological descriptions and illustrations of the new species are provided, and a key to South American species of the genus is given. PMID- 26269823 TI - A new species of small tree frog, genus Dendropsophus (Anura: Hylidae) from the eastern Amazon lowlands of Ecuador. AB - We describe a new species of the hylid frog genus Dendropsophus from Amazonian Ecuador. The new species, Dendropsophus shiwiarum sp. nov., appears to be part of the D. microcephalus species group. Dendropsophus shiwiarum differs from its congeners by a combination of: (1) tympanic membrane non-differentiated and annulus evident only ventrally, (2) disc of Finger III and Toe IV with pointed tip, (3) dorsal surfaces of digital discs with a conical tubercle as result of projection of distal phalanx, and (4) small size (SVL < 19 mm). The new species is morphologically most similar to Dendropsophus riveroi. Examination of the type material of the latter suggests that some Ecuadorian populations reported as D. riveroi were misidentified and in fact belong to D. shiwiarum sp. nov. PMID- 26269824 TI - Heterodera fengi n. sp. (Nematoda: Heteroderinae) from bamboo in Guangdong Province, China--a new cyst nematode in the Cyperi group. AB - Heteroderafengi n. sp. is described and illustrated from bamboo (Phyllostachys pubescens Mazel) based on morphology and molecular analyses of rRNA LSU D2D3 region and ITS. This new species belongs to the Cyperi group. Cysts are characterized by prominent vulval cone with ambifenestrate, bifurcate underbridge that is thicker in middle and a 47.0 (40.0-60.0) um long vulval slit, but without bullae. The second-stage juveniles are characterized by a 23.2 (22.0-24.0) um long stylet with slightly projected or anteriorly flattened knobs, three incisures in lateral field, a 70.2 (62.5-77.0) um long tail with bluntly rounded terminus and hyaline portion ca 58.9 (50.0-62.5)% of the tail length. Males are characterized by a 25.1 (24.5-26.3) um long stylet with rounded knobs sloping posteriorly, four incisures in lateral field, a 29.8 (27.5-31.3) um long spicule with bifurcate tip. Phylogenetic analysis shows that the species has unique D2D3 and ITS rRNA sequences and RFLP-ITS-rRNA profiles. Heteroderafengi n. sp. is closest to H. elachista in dendrograms inferred from both DNA sequences. PMID- 26269825 TI - A new yellow species of glassfrog (Centrolenidae: Nymphargus) from the Amazonian slopes of the Ecuadorian Andes. AB - I describe a new glassfrog from the cloud forest of the Andes of southwestern Ecuador (Plan de Milagro-Gualaceo road; 3.0077 degrees S, 78.53318 degrees W), at elevations between 2140-2160 m. The new species is distinguished mostly by having a pale yellow dorsal coloration instead of the green that characterizes most centrolenids. Morphological traits (i.e., reduced webbing between Fingers III and IV and lack of humeral spines) support the placement of the new species in the genus Nymphargus. PMID- 26269826 TI - A cladistic analysis and classification of the subfamily Bembicinae (Hymenoptera: Crabronidae), with a key to the genera. AB - A cladistic analysis of the digger wasp subfamily Bembicinae based on morphological characters is presented. The underlying data matrix comprises 83 terminal taxa (coded on genus-level) and 64 morphological characters. The resulting strict consensus tree was used as the basis for a revised tribal and subtribal classification of the Bembicinae. Based on a previously published classification, we herewith propose a change: the tribe Heliocausini Handlirsch 1925, stat. resurr. (composed of Acanthocausus Fritz & Toro 1977, Heliocausus Kohl 1892, and Tiguipa Fritz & Toro 1976) is separated from Bembicini Latreille 1802. Four tribes are recognized within the subfamily Bembicinae and seven subtribes within the tribe Gorytini and two subtribes in the tribe Nyssonini, based on the present cladistic analysis.The subtribe Nurseina Nemkov & Lelej, subtrib. nov. (comprising of Nippononysson Yasumatsu & Maidl 1936 and Nursea Cameron 1902) is separated from other genera in the tribe Nyssonini Latreille 1804. An new identification key to the genera of the Bembicinae is provided. PMID- 26269827 TI - Diversity and biogeography of Israeli geophilomorph centipedes (Chilopoda: Geophilomorpha). AB - The fauna of Chilopoda Geophilomorpha of Israel has been analyzed after examining 128 new specimens from 35 localities, reinterpreting all published data including 103 records, and relating occurrence of species with major climatic parameters. A key to identification has been compiled. A total of 17 species are distinguished, of which three are reported from Israel for the first time, while five are documented by published records only. The following new synonymies are proposed and discussed: Dignathodon pachypus Verhoeff, 1943 = Dignathodon microcephalus (Lucas, 1846); Geophilus flavidus noduliger Verhoeff, 1925 = Clinopodes escherichii (Verhoeff, 1896); Pachymerium ferrugineum vosseleri Verhoeff, 1902 = P. ferrugineum (Koch, 1835). Of all the species, Bothriogaster signata and Pachymerium ferrugineum are widespread in the country, while other species occupy different climatic zones, from desert to more humid and montane. PMID- 26269828 TI - Two new species of Eunice Cuvier, 1817 (Polychaeta, Eunicidae) from the coral reefs of Hainan Island with a key to 16 species of Eunice from China seas. AB - A taxonomic study of Eunice species based on material deposited in the Marine Biological Museum of the Chinese Academy of Sciences (MBMCAS) including recently collected specimens from coastal regions of Hainan Island, yielded two new species: Eunice hainanensis n. sp. and E. carrerai n. sp. Both species were collected from dead coral rocks in the reefs of the coastal region of Hainan Island, northern South China Sea. Eunice hainanensis has translucent bidentate subacicular hooks and branchiae present over an extensive region of the body. Within the Eunice group possessing these characters, the new species highly resembles E. schizobranchia Claparede, 1870 in having a numerous chaetigers and a very late start of branchiae (348-570 chaetigers with branchiae from chaetigers 69-72 vs. 731 chaetigers with branchiae from chaetiger 67). However, the two species differ by the presence of the maxillary plate VI (MxVI) in the new species (vs. absent in the latter). Besides, E. hainanensis is much smaller (1.7 1.9 mm vs. 5 mm in maximal width). Eunice carrerai belongs to the Eunice group that has dark bidentate subacicular hooks and branchiae present over an extensive region of the body. It can be distinguished from similar congeners that have the branchiae starting from chaetigers 3-4 and prostomial appendages with moniliform articulations by a combination of characters such as the presence of MxVI, notopodial articulations limited to anterior chaetigers, peristomial cirri articulated and extending to anterior edge of first peristomial ring. A key to 16 species of Eunice identified from China seas in the material examined with notes on their distribution is provided. The major characters of these species are briefly summarized. PMID- 26269829 TI - Thampramon tonvuthi, a new genus and new species of cavernicolous crab (Crustacea: Decapoda: Brachyura: Potamidae) from Thailand. AB - A new genus and species of potamid cavernicolous crab, Thampramon tonvuthi sp. nov., is described from Thailand. While superficially similar to Tiwaripotamon Bott, 1970, Phaibulamon Ng, 1992, and Nemoron Ng, 1996, the new genus possesses a unique combination of morphological characters including a distinctive carapace form, possession of a relatively long third maxilliped exopod, long ambulatory legs and a unique male first gonopod. PMID- 26269830 TI - Idionyx (Odonata: Corduliidae) of the Western Ghats with a description of a new species. AB - The status and distribution of Idionyx Hagen, 1867 (Odonata: Corduliidae), of the Western Ghats, India, is updated and a new species Idionyx gomantakensis is described and illustrated based on male and female specimens from Kulem (= Collem), Goa, India. This new species can be differentiated from other species of Idionyx by long and slender cerci and epiproct, absence of teeth in the basal half of the cerci, and a tuft of golden hairs at the end of the lateral lobes of the epiproct. A revised key to the species of the genus is provided, and its diversity and ecology in the Western Ghats is discussed. PMID- 26269831 TI - A new species of Scandarma (Crustacea: Brachyura: Sesarmidae) from Sabah, Borneo, Malaysia. AB - A new species of terrestrial sesarmid crab, Scandarma raymondi, is described from Sabah, Malaysia. This is the third species in the genus; others are from Taiwan, Japan and Sarawak, Borneo. The new species differs from congeners in the live coloration, proportions of the carapace and ambulatory legs and morphologies of the male abdomen, chela and male first gonopod. PMID- 26269832 TI - Oxybleptes davisi (Notman, 1924) in Minnesota (Coleoptera, Staphylinidae, Staphylininae, Xantholinini). AB - The occurrence of numerous male specimens of Oxybleptes davisi (Notman, 1924) near Duluth in northern Minnesota is reported, including the special collecting circumstances. This is the first record of Oxybleptes davisi in Minnesota, which extends the distributional range of the species considerably toward the west. PMID- 26269833 TI - Trogophloeus tripunctulatus Coiffait, 1981, a new synonym of Carpelimus insularis (Kraatz, 1858) (Coleoptera: Staphylinidae: Oxytelinae). PMID- 26269834 TI - Corrections to a recently published area taxonomy of Australia. PMID- 26269835 TI - A revision of the genus Baeocera in Japan, with a new genus of the tribe Scaphisomatini (Coleoptera, Staphylinidae, Scaphidiinae). AB - The Japanese species of the genus Baeocera Erichson, 1845 are reviewed and a new genus Baeoceroxidium is established for Baeocera micros (Achard, 1923) and members of the Baeocera pilifera species group. The female genitalia are used for the first time in Baeocera for both, as species specific characteristics and to indicate relationships. Amaloceroschema Lobl, 1967 is placed in synonymy with Baeocera. PMID- 26269836 TI - Synopsis of Paxillus MacLeay, 1819 (Coleoptera: Passalidae): distributional records and descriptions of four new species from Brazil. AB - Paxillus MacLeay, 1819 (Coleoptera: Passalidae) is redescribed, with new distributional records and descriptions of four species from Brazil. Paxillus reyesi new species is characterized by the first antennomere of antennal club reduced, slightly longer than half of the second antennomere; mesosternal scar straight, wide and deep. Paxillus chapadensis new species from the Chapada dos Guimaraes (Mato Grosso, Brazil) has prostenal process centrally impressed with an opaque depression; and the scape of the antenna with a subapical dorsal spine, shallow ventral depression, and few erect setae. Paxillus manausensis new species from Manaus (Amazonas, Brazil) has high frontal ridges; mid-frontal tubercles high, acuminate and larger than the internal tubercles; and the central tubercle short. Paxillus uaupesensis new species from Uaupes (Amazonas, Brazil) has the mesosternal scar opaque, elongate and depressed; and the scutellum depressed. Diagnostic redescriptions and illustrations of known species from Brazil, a key to all known species, and a checklist with distributional data are provided. PMID- 26269837 TI - New retroplumid crabs (Crustacea, Brachyura, Retroplumidae Gill, 1894) from the Eocene of Huesca (Aragon, Spain). AB - Two new brachyurans assignable to the family Retroplumidae Gill, 1894, Serrablopluma diminuta n. gen., n. sp., and Gaudipluma bacamortensis n. gen., n. sp., from the Eocene of northern Spain (Huesca, Aragon), substantially enlarge our current knowledge of the morphological diversity of the family. The material, with well-preserved ventral surfaces, permits the erection of two new genera that can be referred to the family with confidence on the basis of the general carapace shape, narrow front, a reduced last pair of pereiopods and characteristic thoracic sternum (broad, trapezoidal sternites 3, 4, subrectangular sternites 5-7, sternite 8 conspicuously reduced and inclined). Serrablopluma diminuta n. gen., n. sp. co-occurs with two other retroplumids in the most diverse fossil assemblage of that family known to date. PMID- 26269838 TI - Review of Neoperla (Plecoptera: Perlidae) from Zhejiang Province, China. AB - The species of the perlid genus Neoperla are reviewed from eastern coastal Zhejiang Province, China. Neoperla xuanson- gae sp. nov. is described and compared with related congeners. Neoperla yangae Du is considered a junior synonym of N. anjiensis Yang & Yang and the first record of N. flagellata Li & Muranyi is given for the Province. Several additional species are redescribed or diagnosed. A provisional key to the known species for Zhejiang Province is also presented. PMID- 26269839 TI - Caribboecetes progreso, a new species of sand-dwelling amphipod (Amphipoda: Corophiidea: Ischyroceridae) from the Gulf of Mexico, with a key for the genus. AB - A new species of the genus Caribboecetes Just, 1983 is described and illustrated from specimens collected on sandy bottoms of the northern Yucatan Peninsula, southeastern Gulf of Mexico. Caribboecetes progreso sp. nov. differs from the closely related species Caribboecetes barbadensis Just, 1983 and Caribboecetes jenikarpae Just, 1984 by the inflated triangular anterolateral flange on basis of gnathopod 2, and from Caribboecetes justi Ortiz & Lemaitre, 1997 by the setose anterolateral surface of coxal plate 7 and basis of pereopod 7. Ecological notes for the new species, a morphological comparison, map of distribution and key for all members in the genus are also provided. PMID- 26269840 TI - Compositermes vindai (Isoptera: Termitidae: Apicotermitinae), a new genus and species of soldierless termite from the Neotropics. AB - The New World Anoplotermes group is a common and diverse clade of soil-dwelling soldierless termites that is undergoing needed taxonomic reclassification. Based on robust worker gut morphology centered near the enteric valve, a new genus and its singular species, Compositermes vindai, are described from collections encompassing a massive expanse of tropical America. The enteric valve armature is thought to enhance inoculation of the food stream with symbiotic bacteria. PMID- 26269842 TI - Paranotocoris Ahmad & Shadab, 1973, a new synonym of Phyllomorpha Laporte, 1833 (Hemiptera: Heteroptera: Coreidae). PMID- 26269841 TI - On the identity of Julus rimosus Karsch, 1881 (Diplopoda, Julida, Julidae), the only schizophylline known from Libya (North Africa) and notes on Libyan millipedes. PMID- 26269843 TI - A review of the genus Pelenomus Thomson (Coleoptera: Curculionidae: Ceutorhynchinae) from China. AB - The genus Pelenomus Thomson from China is revised and six species are found occurring in China. Among them, P. curvatus, sp. nov. is described from Yunnan province, and four species are newly recorded from China: P waltoni (Boheman, 1843), P. canaliculatus (Fahraeus, 1843), P. quadricorniger (Colonnelli, 1986) and P roelofsi (Hustache, 1916). Taxonomic diagnosis, habitus photos, detailed illustrations and distribution map of each species are provided, as well as a key to all the Chinese species. This study raised the number of Chinese Pelenomus from one to six species. PMID- 26269844 TI - Two new paralcyoniid octocorals from Japan (Anthozoa: Alcyonacea). AB - Two new species of paralcyoniid octocorals are described from Japan. One of them, Ceeceenus retractus n. sp., is the fifth species of the genus, and the other, Nanalcyon sagamiense n. gen. n. sp., is proposed as a new genus. Nanalcyon is similar to the Mediterranean and Atlantic genera Maasella Poche, 1914 and Paralcyonium Milne Edwards and Haime, 1850, but the new genus clearly differs from these in having independent colonies not joined by stolons. The ultrastructure of the sclerites is compared among the new genus, Ceeceenus and Paralcyonium by means of SEM. All three genera display the same three main types of sclerites, flat platelets, rods and spindles, the ultrastructure of all consisting of non-branching fibrous crystals. In addition to these, two genera, Ceeceenus and Paralcyonium, have flat oval platelets with the ultrastructure showing branching dendritic crystals, lacking in Nanalcyon. PMID- 26269845 TI - Description of Alpheus buckupi spec. nov., a new amphi-Atlantic snapping shrimp (Caridea: Alpheidae), based on morphological and molecular data. AB - A new amphi-Atlantic snapping shrimp of the genus Alpheus Fabricius, 1798, Alpheus buckupi spec. nov., is described and illustrated based on material collected from the western (Orinoco Delta, Venezuela to Sao Paulo, Brazil) and eastern Atlantic (Sao Tome and Principe). The new species is morphologically similar to members of the A. lobidens De Haan, 1850 species complex, from the Indo-Pacific, including A. inopinatus Holthuis & Gottlieb, 1958 from the eastern Mediterranean, and the Red Sea to Pakistan, especially based on major and minor chelae configuration. We also characterized this new species in terms of DNA sequences of a ribosomal 16S subunit and compared it in a phylogenetic context. These analyses showed a clear separation of the specimens of A. buckupi spec. nov. from similar species of the A. edwardsii (Audouin, 1826) species group, including some morphologically close species such as A. cf. lobidens, A. heterochaelis Say, 1818, A. pontederiae de Rochebrune, 1883, A. sp. aff. euphrosyne De Man, 1897, and A. microrhynchus De Man, 1897. PMID- 26269846 TI - A new semi-subterranean diving beetle of the Hydroporus normandi-complex from south-eastern France, with notes on other taxa of the complex (Coleoptera: Dytiscidae). AB - Hydroporus galloprovincialis sp. n. is described from Jouques, north-east of Aix en-Provence in south-eastern France (Provence). The new species belongs to the Hydroporus memnonius-group, within which it is the only ascertained normandi complex species of the French fauna. The habitat (small springs) and morphological features of the species suggest a semi-subterranean life style. It can be separated from the other species of the complex notably by its more elongated and parallel-sided habitus, by its wider pronotum and flatter dorsal surface, and furthermore differs from H. normandi Regimbart, 1903 by a different shape of the gonocoxa. Illustrations are provided for other described normandi complex species and subspecies for comparison. Analyses of partial cox1 sequences indicate that the three sampled H. normandi-complex species (H. galloprovincialis sp. n., H. normandi and H. lluci Fery, 1999) diverged recently; their relationships are unresolved. H. galloprovincialis sp. n. is for the moment the only species of the genus Hydroporus Clairville, 1806 endemic to continental France. PMID- 26269691 TI - Search for the Standard Model Higgs boson produced in association with top quarks and decaying into [Formula: see text] in [Formula: see text] collisions at [Formula: see text] with the ATLAS detector. AB - A search for the Standard Model Higgs boson produced in association with a top quark pair, [Formula: see text], is presented. The analysis uses 20.3 fb-1 of pp collision data at [Formula: see text], collected with the ATLAS detector at the Large Hadron Collider during 2012. The search is designed for the [Formula: see text] decay mode and uses events containing one or two electrons or muons. In order to improve the sensitivity of the search, events are categorised according to their jet and b-tagged jet multiplicities. A neural network is used to discriminate between signal and background events, the latter being dominated by [Formula: see text]+jets production. In the single-lepton channel, variables calculated using a matrix element method are included as inputs to the neural network to improve discrimination of the irreducible [Formula: see text] background. No significant excess of events above the background expectation is found and an observed (expected) limit of 3.4 (2.2) times the Standard Model cross section is obtained at 95 % confidence level. The ratio of the measured [Formula: see text] signal cross section to the Standard Model expectation is found to be [Formula: see text] assuming a Higgs boson mass of 125[Formula: see text]. PMID- 26269847 TI - Redescription of Astyanax guaporensis Eigenmann, 1911 (Characiformes: Characidae), a small characid from the rio Madeira basin. AB - During recent expeditions to several localities in the rio Madeira basin, a poorly known species of Characidae described more than a century ago, Astyanax guaporensis Eigenmann, was collected. The species is herein redescribed based on the type material and many recently collected specimens. The species seems to occur only in the rio Madeira basin, rio Amazonas drainage. The species is mainly recognized among its congeners by having five to nine maxillary teeth, a series of V-shaped marks on the midlateral line of body, and the absence of a black mark on the caudal peduncle. PMID- 26269848 TI - Subterranean species of Acipes Attems, 1937 (Diplopoda, Julida, Blaniulidae). AB - Two new blind, cave-dwelling species of the genus Acipes Attems, 1937, are described from the Algarve, southern Portugal: A. machadoi n. sp. and A. bifilum n. sp. Acipes andalusius Enghoff & Mauries, 1999, is reported from the mesovoid shallow substratum in Alicante (Spain), 250 km from the type locality in Andalusia. PMID- 26269850 TI - CLARK W. BEASLEY (1942-2012). PMID- 26269849 TI - The identity of the enigmatic genus Stenocolletes Schrottky (Hymenoptera: Tiphiidae). AB - The identity of Stenocolletes Schrottky and its single species, Stenocolletespictus Schrottky, has remained a mystery since their description in 1909. Stenocolletes was originally placed in the bee family Colletidae but no known American colletid matches the original description. The type of S. pictus is likely lost as are large portions of Schrottky's collection. Herein, we describe and designate as neotype a historic specimen that closely matches Schrottky's description and place it in the current classification. Stenocolletes pictus is conspecific with the South American thiipid wasp Calchaquila albinervis (Brethes, 1913). Both generic and specific names are new synonymous of Stenocolletes and pictus, respectively (new ju- nior synonym). Stenocolletes pictus is also recorded for the first time from C6rdoba, Argentina. PMID- 26269853 TI - Micromoina arboricola n. gen., n. spec. (Crustacea: Cladocera), a new moinid living in a forest tree-hole in Minas Gerais, Brazil. AB - With a maximum size of ca 0.5 mm, Micromoina arboricola is among the smallest moinids known to date. It was discovered in a flooded treehole in a forest in the Medio Rio Doce Valley, Minas Gerais, Brazil, where it mainly feeds on particulate organic matter derived from the vinhatico tree . However, it is easily cultured in the lab on a diet of green algae plus yeast and pelleted fish food. Structurally, it is a miniature version of a moinid, distinguished by characters on the antennules (both sexes) and the postabdomen. The latter is peculiar in shape, in lacking a basal spine, and in having only three lateral plumose setae. A comparative investigation of the barcoding fragment of the COI gene in a number of moinids confirms the family Moinidae as composed of several genera, as well as the status of the new taxon. PMID- 26269851 TI - A new species of the Gekko japonicus group (Squamata: Sauria: Gekkonidae) from the border region between China and Vietnam. AB - We describe a new species of the genus Gekko on the basis of 25 specimens from southern China and northern Vietnam. Gekko adleri sp. nov. is distinguished from the remaining congeners by a combination of the following characters: size moderate (SVL < 80 mm); nares in contact with rostral; internasal single, smaller than supranasal; postmentals enlarged; interorbital scales between anterior corners of the eyes 27-36; dorsal tubercle rows 7-11; ventral scales between mental and cloacal slit 168-190; midbody scale rows 123-144; ventral scale rows 35-44; subdigital lamellae on first toe 11-14, on fourth toe 11-15; finger and toe webbing present at base; tubercles absent on upper surface of fore limbs; tubercles on tibia 0-8; precloacal pores 17-21 in males; postcloacal tubercle single; tubercles present on dorsal surface of tail base; subcaudals enlarged; dorsal surface of body with four or five narrow light bands between shoulder and sacrum. PMID- 26269855 TI - New species of Lebiasina (Ostariophysi: Characiformes: Lebiasinidae) from the upper Mazaruni River drainage, Guyana. AB - Lebiasina ardilai is described from the upper Mazaruni in Guyana. The new species differs from all its congeners by its color pattern consisting of: a narrow, nearly straight primary stripe, extending from posterior to humeral blotch to near the vertical through anal-fin origin, being absent or inconspicuous in females and conspicuously marked in males; the presence of four series of dark blotches at the distal border of the scales of longitudinal series 2-5; the faint secondary stripe running onto scales of second and third longitudinal row of scales; intermediate stripe absent; and the posteriorly displaced caudal blotch, not reaching the posterior tip of caudal peduncle. PMID- 26269856 TI - Bromelicolous Polypedilum Kieffer from South Brazil (Diptera: Chironomidae). AB - Polypedilum (s. str.) kaingangi sp. n. is described and figured as male, female, pupa and larva and the female and immature stages of Polypedilum (s. str.) solimoes Bidawid-Kafka, 1996 are described and illustrated. The immatures of both species inhabit leaf axils of various bromeliad species in the Atlantic rainforest in Santa Catarina State, South Brazil. PMID- 26269852 TI - A survey of the genus Sorolopha Lower, 1901 in the northern part of Vietnam (Lepidoptera: Tortricidae, Olethreutinae). AB - A survey of the genus Sorolopha Lower, 1901 in the northern part of Vietnam revealed the presence of 10 species, including S. cucphuongensis Bae & Le, sp. nov. Most of the species previously were reported by various authors, but S. rubescens Diakonoff, 1973 and S. cyclotoma Lower, 1901 are newly recorded for the country. All species are diagnosed, and figures of the adults and genitalia are provided, along with a key to species of Sorolopha in Vietnam. PMID- 26269854 TI - The rediscovery of Oplurus bibronii Guichenot, 1848 a valid species of the liolaemid genus Phymaturus (Iguania: Liolaemidae). AB - Oplurus bibronii was a species described more than 160 years ago from the highlands of Ovalle, Chile. The species was earlier synonymized with Phymaturus palluma and since then its taxonomic status has not been re-examined. In February of 2011, we were successful in capturing specimens of Phymaturus in the highlands of Ovalle and additionally we examined high quality digital pictures of the type series of O. bibronii. Our analysis shows that the type series is composed of two different species, one of which overlaps their diagnostic characters with the characters of the specimens collected in the highlands of Ovalle, and therefore they correspond to Phymaturus bibronii (new combination). In addition, our review of the holotype, and some paratypes and topotypes of the recently described P. paihuanense shows that this is a junior synonym of P. bibronii. PMID- 26269857 TI - Description of the female of Aysha yacupoi Brescovit 1992 (Araneae: Anyphaenidae). AB - The female of Aysha yacupoi Brescovit, 1992 is described and illustrated for the first time. Males and female specimens were observed together in the same plants. Some data on natural history are presented. PMID- 26269858 TI - Discovery of a new species of the genus Planaeschna from Northern Vietnam, with a first description of male P. tomokunii. AB - A new species of Planaeschna McLachlan, P. guentherpetersi sp. nov. (holotype male and paratype female) from Phu Tho province, northern Vietnam, is described and illustrated. In addition, the male of P. tomokunii Asahina, 1996, which was known from only the holotype female, is described for the first time, based on newly collected material of both sexes, from the type locality, Tam Dao, Vinh Phuc province, northern Vietnam. PMID- 26269859 TI - New species of Xestochironomus Sublette et Wirth, 1972 (Diptera: Chironomidae) from Atlantic Forest, Brazil. AB - Two new Xestochironomus species, X. dickinsoni sp. n. and X. virgoferreae sp. n., from Brazilian Atlantic Forest are described, based on male adults. Additionally, a key to adult males of the genus is provided. PMID- 26269930 TI - Percutaneous transhepatic cholangioscopy for indeterminate biliary strictures using the SpyGlass system: a case series. AB - Peroral cholangioscopy is useful in differentiating benign from malignant biliary strictures. However, when conventional biliary access via endoscopic retrograde cholangiopancreatography (ERCP) fails, percutaneous transhepatic cholangioscopy (PTCS) via the SpyGlass cholangioscopy system can be used to achieve a diagnosis. Four patients with biliary strictures in whom conventional ERCP was not possible and percutaneous brushings were either nondiagnostic or unsatisfactory were investigated with PTCS. The technique of PTCS involves insertion of the SpyGlass cholangioscope through a percutaneous transhepatic sheath, placed just prior to the procedure, to visualize the stricture and obtain biopsies with the SpyBite forceps. On the basis of our early observations, we conclude that PTCS using the SpyGlass cholangioscopy system for the assessment of biliary strictures is feasible, safe, and provides high diagnostic accuracy. PMID- 26269931 TI - Two new species of Rhinebothrium (Cestoda: Rhinebothriidea) from granulated guitarfish Glaucostegus granulatus in the Gulf of Oman. AB - During a study of the rhinebothriideans of rays in the Gulf of Oman, two new species of Rhinebothrium Linton, 1890, Rhinebothrium kruppi sp. n. and R. persicum sp. n., were identified in Glaucostegus granulatus (Cuvier). Some significant features that distinguish R. kruppi sp. n. from R. persicum sp. n. include: scolex characteristics (hinged with 42-46 loculi vs. fusiform with 68-62 loculi), number of testes (4-5 vs. 20-27), genital pore position (61.1-76.9% of proglottid length vs. 47.2-63.3%), ovarian morphology (lobulated vs. follicular), cirrus-sac expansion (past midline of proglottid vs. limited to poral side of proglottid), vas deferens configuration (spanning posteriorly to near ovarian isthmus vs. to the level of ovarian anterior margins) and details of microthrix morphology. In addition, a combination of the aforementioned characteristics can be used to distinguish these two new species from other valid species of Rhinebothrium. These are the first species of rhinebothriidean cestodes to be described systematically from the Gulf of Oman, Iran. The two new species reported here increase the number of valid species of Rhinebothrium to 43. PMID- 26269932 TI - Prognostic Factors of Cholangiocarcinoma After Surgical Resection: A Retrospective Study of 293 Patients. AB - BACKGROUND: Cholangiocarcinoma is one of the most common malignancies in China. Surgical resection is the only treatment option; however, diagnosis at advanced stage precludes surgery. Comprehensive knowledge of prognostic markers is missing. Hence, the aim of this study was to determine clinicopathological indexes that would be indicative of prognosis in post-operative cases of cholangiocarcinoma. MATERIAL AND METHODS: A retrospective analysis of 293 cases of cholangiocarcinoma patients attending the 301 Military Hospital in Beijing, China between January 2004 and December 2010 were included in the study. The patients had follow-up history until August 2012. Cox proportional hazards model analysis was performed to identify indexes of prognosis. All indicators were analyzed by univariate and multivariate analysis. RESULTS: The median follow-up time was 55.90 months, with recurrence and metastasis in 162 cases (55.3%) and death in 223 cases (76.1%). The 1-year, 3-year, and 5-year survival rates were 71.7%, 38.2%, and 10.6%, respectively. The independent risk factors of overall survival were degree of tumor differentiation, TNM stage, surgical margin, intraoperative blood transfusion, tumor location, alkaline phosphatase levels in blood, and relapse. CONCLUSIONS: Good prognosis in cholangiocarcinoma patients is indicated by highly differentiated tumor, early stages of TNM staging, no resection margin invaded, no intraoperative blood transfusion, intrahepatic tumor, normal alkaline phosphatase levels, and no relapse. PMID- 26269933 TI - Correlation Between Recurrent Subconjunctival Hemorrhages and Conjunctivochalasis by Clinical Profile and Successful Surgical Outcome. AB - OBJECTIVE: To characterize the clinical profile of patients with recurrent subconjunctival hemorrhages (SCHs) and evaluate the effect of conjunctivochalasis (CCh) surgery on disease recurrences. METHODS: Three hundred and sixty-two patients with SCHs (mean age, 56.4+/-16.0 years) were enrolled in this multicenter epidemiologic study. The severity of CCh, lifestyle at the time of SCH onset, and the frequency of previous SCHs were compared. Thirty-eight patients with 2 or more episodes of SCHs (mean age, 68.2+/-8.9 years) underwent surgery for CCh. The effectiveness of surgery was evaluated by comparing the frequency of SCH preoperatively and postoperatively. RESULTS: Patients with three or more recurrent SCHs showed a significantly (P=0.003) higher grade of CCh and tended to be engaged in activities that require visual concentration, such as watching a visual display terminal, knitting, reading, and driving. More than 80% of eyes that underwent surgery to CCh showed no recurrence of the hemorrhages, and the frequency of SCH significantly (P<0.0001) decreased postoperatively. CONCLUSIONS: Moderate or severe CCh and activities that may cause dry eye can be considered to be risk factors for recurrent SCHs. Surgery to treat CCh is a useful option for patients with frequent recurrences of SCHs. PMID- 26269934 TI - Blood Compatibility Evaluations of Fluorescent Carbon Dots. AB - Because of their unique advantages, fluorescent carbon dots are gaining popularity in various biomedical applications. For these applications, good biosafety is a prerequisite for their use in vivo. Studies have reported the preliminary biocompatibility evaluations of fluorescent carbon dots (mainly cytotoxicity); however, to date, little information is available about their hemocompatibility, which could impede their development from laboratory to bedside. In this work, we evaluated the hemocompatibility of fluorescent carbon dots, which we prepared by hydrothermal carbonization of alpha-cyclodextrin. The effects of the carbon dots on the structure and function of key blood components were investigated at cellular and molecular levels. In particular, we considered the morphology and lysis of human red blood cells, the structure and conformation of the plasma protein fibrinogen, the complement activation, platelet activation, and in vitro and in vivo blood coagulation. We found that the carbon dots have obvious concentration-dependent effects on the blood components. Overall, concentrations of the fluorescent carbon dots at <=0.1 mg/mL had few adverse effects on the blood components, but at higher doses, the carbon dots impair the structure and function of the blood components, causing morphological disruptions and lysis of red blood cells, interference in the local microenvironments of fibrinogen, activation of the complement system, and disturbances in the plasma and whole blood coagulation function in vitro. However, the carbon dots tend to activate platelets only at low concentrations. Intravenous administration of the carbon dots at doses up to 50 mg/kg did not impair the blood coagulation function. These results provide valuable information for the clinical application of fluorescent carbon dots. PMID- 26269935 TI - Food Impaction and Periodontal/Peri-Implant Tissue Conditions in Relation to the Embrasure Dimensions Between Implant-Supported Fixed Dental Prostheses and Adjacent Teeth: A Cross-Sectional Study. AB - BACKGROUND: Food impaction and periodontal/peri-implant tissue conditions were evaluated in relation to the embrasure dimensions between implant-supported fixed dental prostheses (FDPs) and adjacent teeth. METHODS: A total of 215 embrasures of 150 FDPs in 100 patients (55 males and 45 females, aged 27 to 83 years; mean age: 56 years) were included in the study. Clinical assessments of the periodontal/peri-implant mucosal conditions, radiographic assessments of embrasure dimensions, and overall patient satisfaction were used as explanatory variables for the food impaction and periodontal/peri-implant tissue conditions adjacent to implant-supported FDPs in the generalized estimating equation (GEE) analysis. RESULTS: Food impaction was reported in 96 (44.7%) of 215 embrasures between implant-supported FDPs and adjacent teeth. Food impaction was reported more frequently in the embrasures with proximal contact loss than in those with tight contact (P = 0.009). Overall patient satisfaction was influenced negatively by food impaction in the proximal embrasures (P = 0.01). Among embrasure dimensions, only the embrasure surface area (ESA) significantly influenced food impaction (P = 0.03). Significant influences of various embrasure dimensions on the periodontal/peri-implant mucosal conditions and bone level at the implant were found in the univariate and multivariate GEE analyses. CONCLUSIONS: Food impaction between implant-supported FDPs and adjacent teeth occurred more frequently when proximal contact was lost and ESA increased. Food impaction negatively affected overall patient satisfaction. Embrasure dimensions influenced the periodontal/peri-implant mucosal conditions and bone level at the implant. PMID- 26269938 TI - Obituary: Clifford Ochsenbein, DDS. PMID- 26269936 TI - Effectiveness of Laser Application for Periodontal Surgical Therapy: Systematic Review and Meta-Analysis. AB - BACKGROUND: Evidence has shown some improved clinical outcomes and morbidity reduction with the use of lasers for non-surgical periodontal therapy due to ablation, vaporization, hemostasis, and field sterilization. The purpose of this systematic review is to evaluate and compare studies involving lasers as monotherapy or adjunctive to surgical periodontal treatment. METHODS: Electronic and manual searches were conducted by two independent reviewers in several databases for articles written in English up to December 2014. Articles were included in this review if they reported outcomes of surgical periodontal therapy with and without the use of lasers. The primary outcome was probing depth (PD), and secondary outcomes were measured changes in clinical factors such as clinical attachment level (CAL) and gingival recession (GR). For the comparative studies included, the pooled weighted mean difference (WMD) and 95% confidence interval (CI) of each variable were calculated using random-effects meta-analysis. RESULTS: Eight and nine articles were included in the quantitative and qualitative analyses, respectively. Although low-to-moderate risk of bias was detected, high heterogeneity among studies was found. In flap surgery with or without laser treatment, there was no statistically significant difference in primary outcome. Similarly, in guided tissue regeneration (GTR)/enamel matrix derivative (EMD) with and without laser treatment, the WMD of PD was negligible; however, the GTR/EMD group showed better outcomes (P = 0.005) than the laser group. Regarding the secondary outcomes, in the flap surgery group, the WMD of CAL gain was 1.34 mm, and the WMD of GR was -0.24 mm; no significant difference was detected between groups. In GTR/EMD with and without laser treatment, the WMD of CAL gain was 0.10 mm and the WMD of recession was -0.18 mm; again, no significant difference was detected between groups. CONCLUSIONS: The available evidence is insufficient to support the effectiveness of dental lasers as an adjunct to resective or regenerative surgical periodontal therapy. However, precautions must be exercised when interpreting the results of this study because of the small sample size and high heterogeneity among studies. PMID- 26269939 TI - Physiologic Levels of Endogenous Hydrogen Sulfide Maintain the Proliferation and Differentiation Capacity of Periodontal Ligament Stem Cells. AB - BACKGROUND: Many invading oral bacteria are known to produce considerable amounts of hydrogen sulfide (H2S). The toxic activity of exogenous H2S in periodontal tissue has been demonstrated, but the role of endogenous H2S in the physiologic function of periodontal tissue remains poorly understood. The purpose of the present study is to investigate the biologic functions of H2S in the proliferation and differentiation of human periodontal ligament stem cells (PDLSCs). METHODS: PDLSCs were isolated from periodontal ligament tissues of periodontally healthy volunteers or patients with periodontitis. Immunocytochemical staining, flow cytometry, and Western blot analysis were used to examine the expression of H2S-synthesizing enzymes cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE). The proliferation capacity of PDLSCs was determined by cell counting kit-8 assay, carboxyfluorescein succinimidyl ester analysis, and 5-ethynyl-2'-deoxyuridine assay. The osteogenic potential of PDLSCs was tested using alkaline phosphatase staining, Alizarin Red staining, and in vivo transplantation experiments. Oil Red O staining was used to analyze adipogenic ability. RESULTS: The results show that human PDLSCs express both CBS and CSE and produce H2S. Blocking the generation of endogenous H2S with CBS inhibitor hydroxylamine significantly attenuated PDLSC proliferation and reduced the osteogenic and adipogenic differentiation capacity of PDLSCs. In contrast, CSE inhibitor DL-propargylglycine had no effect on PDLSC function. Exogenous H2S could inhibit the production of endogenous H2S and impair PDLSC function in a dose-dependent manner. CONCLUSION: Physiologic levels of endogenous H2S maintain the proliferation and differentiation capacity of PDLSCs, and CBS may be the main source of endogenous H2S in PDLSCs. PMID- 26269940 TI - Breastfeeding and Childhood Cancer: Is Breastfeeding Preventative to Childhood Cancer? AB - Breastfeeding is well-known to have a protective effect against infection in infants. It has been suggested that breast milk may play a role in the prevention of certain childhood cancer. We investigated this issue in a case-control study comprising 300 patients with childhood cancer. There was 73 patients (24.3%) with leukemia, 82 patients (27.3%) with lymphoma, and 146 patients (48.4%) with solid tumors (brain tumors, neuroblastoma, soft tissue sarcomas, germ cell tumors, renal tumor, bone tumor, retinoblastoma, hepatoblastoma, and others) and 316 controls matched for age and sex. Breastfeeding duration of the control group was found to be significantly longer than the patient group (X(2) = 57.774; P < .001). In conclusion, breastfeeding was found to be inversely associated with pediatric cancer in our study. PMID- 26269941 TI - Commonly Practiced Quality Control and Quality Assurance Procedures for Gas Chromatography-Mass Spectrometry Analysis in Forensic Urine Drug-Testing Laboratories. AB - Forensic urine drug-testing laboratories operate in a prescribed scientific and administrative manner to ensure accurate test results. All specimens positive by an initial immunoassay test must be confirmed by gas chromatography/mass spectrometry (GC/MS). To provide adequate control and verification of these analytical processes, laboratories must implement appropriate policies and procedures to be used in routine practice. This review describes the following topics regarding GC/MS analyses: method validation, instrument performance, assay calibration, quality control, criteria for designating a positive test result, sample and batch acceptance criteria, and GC/MS data review. PMID- 26269942 TI - Evidence Value of Textile Fiber - Transfer and Persistence of Fibers. AB - Fibers comprise probably the most common form of trace evidence in forensic science today. They occur in perhaps one-quarter of all cases that involve trace evidence and a large majority of crime laboratories routinely characterize textile fibers. Although a great deal of research has been done on how to best characterize and compare fibers, relatively little time has been spent on determining the significance of fiber evidence. This article presents a summary of the studies of fiber transfer and persistence and determination of the significance of fiber evidence. This accumulated research and analysis will enable fiber examiners to better interpret evidence in cases where foreign fibers have been transferred during contact between victims and perpetrators of crimes. PMID- 26269943 TI - Forensic Science and the Internet - Current Utilization and Future Potential. AB - The Internet has become a very powerful and inexpensive tool for the free distribution of knowledge and information. It is a learning and research tool, a virtual library without borders and membership requirements, a help desk, and a publication house providing newspapers with current information and journals with instant publication. Very soon, when live audio and video transmission is perfected, the Internet (popularly referred to as the Net) also will be a live classroom and everyday conference site. This article provides a brief overview of the basic structure and essential components of the Internet. A limited number of home pages/Web sites that are already made available on the Net by scientists, laboratories, and colleges in the forensic science community are presented in table forms. Home pages/Web sites containing useful information pertinent to different disciplines of forensic science are also categorized in various tables. The ease and benefits of the Internet use are exemplified by the author's personal experience. Currently, only a few forensic scientists and institutions have made their presence felt. More participation and active contribution and the creation of on-line searchable databases in all specialties of forensic science are urgently needed. Leading forensic journals should take the lead and create on line searchable indexes with abstracts. Creating Internet repositories of unpublished papers is an idea worth looking into. Leading forensic science institutions should also develop use of the Net to provide training and retraining opportunities for forensic scientists. PMID- 26269944 TI - Methods for the Analysis of Human Bite Marks. AB - The comparison of features within a bite mark injury with the dentition of a suspect may be required during the course of a criminal investigation. A review of the literature regarding bite mark analysis has been undertaken to determine the value of this evidence. Bite marks in skin are complex injuries consisting of abrasions, lacerations, and contusions, caused by the crushing action of the teeth and related structures. Front-line investigators need to recognize and interpret these features, but no standard method of information collection or comparison has been agreed. Many classifications of bite mark types have been proposed, but do not appear to aid mark analysis. Investigations of bite strengths and sucking forces have been inconclusive. Insufficient information exists as to the accuracy and reproducibility of the representation of the dentition by tissue pathology. Histological analysis and collagen staining techniques have attempted to define the area of injury in detail, but have limited application. The quality of the mark is determined by numerous intrinsic and extrinsic factors. Distortion and shrinkage of the tissues introduce dimensional disturbances that require elimination before a comparison can be undertaken. No method exists to quantify and correct these distortions. The investigator must be aware that self-inflicted marks often occur among children and that other events may replicate bite mark injuries. The most common bite mark comparison methods employ an intermediate template produced from the suspect dentition that, when overlaid onto a scale photograph of the injury, demonstrates correspondence. No agreement exists regarding the individuality of human dentition, minimum level of correspondence required to positively identify the assailant, and the accuracy to which tissue pathology can represent these details. It is concluded that bite mark comparison can only exclude a suspect and should not be used for positive identification. PMID- 26269945 TI - Modeling the voltage loss mechanisms in lithium-sulfur cells: the importance of electrolyte resistance and precipitation kinetics. AB - Understanding of the complex electrochemical, transport, and phase-change phenomena in Li-S cells requires experimental characterization in tandem with mechanistic modeling. However, existing Li-S models currently contradict some key features of experimental findings, particularly the evolution of cell resistance during discharge. We demonstrate that, by introducing a concentration-dependent electrolyte conductivity, the correct trends in voltage drop due to electrolyte resistance and activation overpotentials are retrieved. In addition, we reveal the existence of an often overlooked potential drop mechanism in the low voltage plateau which originates from the limited rate of Li2S precipitation. PMID- 26269946 TI - Dengue Non-coding RNA: TRIMmed for Transmission. AB - Dengue virus RNA is trimmed by the 5'->3' exoribonuclease XRN1 to produce an abundant, non-coding subgenomic flavivirus RNA (sfRNA) in infected cells. In a recent paper in Science, Manokaran et al. (2015) report that sfRNA binds TRIM25 to evade innate immune sensing of viral RNA by RIG-I. PMID- 26269947 TI - H. pylori GPS: Modulating Host Metabolites for Location Sensing. AB - Almost 20 years ago, urea was described as a chemotaxis attractant for Helicobacter pylori. In this issue of Cell Host & Microbe, Huang et al. (2015) report that H. pylori employs its urease enzyme to destroy urea to bring the concentration into a range that provokes an attractant response. PMID- 26269948 TI - STING Signaling the enERGIC Way. AB - The effector proteins IpaJ and VirA, from the bacterium Shigella flexneri, block the general secretory pathway (GSP) at different stages. In this issue of Cell Host & Microbe, Dobbs et al. (2015) use these proteins as a tool to pinpoint STING trafficking and signaling to the ER-Golgi intermediate compartment (ERGIC). PMID- 26269949 TI - Dectin-1 Exerts Dual Control in the Gut. AB - Dectin-1, a beta-glucan receptor, contributes to host anti-fungal defense. In this issue of Cell Host & Microbe, Tang et al. (2015) show that suppressing Dectin-1 signaling protects mice from experimental colitis by decreasing anti microbial peptide production, which allows overgrowth of Lactobacilli and triggers T regulatory cell expansion in the gut. PMID- 26269950 TI - Sweet Talk: Regulating Glucose Metabolism in Toxoplasma. AB - Toxoplasma gondii, the causative agent of toxoplasmosis, is an intracellular parasite that demonstrates a remarkable ability to adapt to nutrient availability. In this issue of Cell Host & Microbe, Blume et al. (2015) describe the unique role of a gluconeogenic enzyme in regulation of glucose catabolism in T. gondii. PMID- 26269951 TI - Do You Believe in ReincaRNAtion? Herpesviruses Reveal Connection between RNA Decay and Synthesis. AB - Many viruses degrade host mRNAs to reduce competition for proteins/ribosomes and promote viral gene expression. In this issue of Cell Host & Microbe, Abernathy et al. (2015) demonstrate that a herpesviral RNA endonuclease induces host transcriptional repression that is mediated through the decay factor Xrn1 and evaded by viral genes. PMID- 26269952 TI - Chemodetection and Destruction of Host Urea Allows Helicobacter pylori to Locate the Epithelium. AB - The gastric pathogen Helicobacter pylori interacts intimately with the gastric mucosa to avoid the microbicidal acid in the stomach lumen. The cues H. pylori senses to locate and colonize the gastric epithelium have not been well defined. We show that metabolites emanating from human gastric organoids rapidly attract H. pylori. This response is largely controlled by the bacterial chemoreceptor TlpB, and the main attractant emanating from epithelia is urea. Our previous structural analyses show that TlpB binds urea with high affinity. Here we demonstrate that this tight binding controls highly sensitive responses, allowing detection of urea concentrations as low as 50 nM. Attraction to urea requires that H. pylori urease simultaneously destroys the signal. We propose that H. pylori has evolved a sensitive urea chemodetection and destruction system that allows the bacterium to dynamically and locally modify the host environment to locate the epithelium. PMID- 26269953 TI - Posttranslational Modifications of the Master Transcriptional Regulator NPR1 Enable Dynamic but Tight Control of Plant Immune Responses. AB - NPR1, a master regulator of basal and systemic acquired resistance in plants, confers immunity through a transcriptional cascade, which includes transcription activators (e.g., TGA3) and repressors (e.g., WRKY70), leading to the massive induction of antimicrobial genes. How this single protein orchestrates genome wide transcriptional reprogramming in response to immune stimulus remains a major question. Paradoxically, while NPR1 is essential for defense gene induction, its turnover appears to be required for this function, suggesting that NPR1 activity and degradation are dynamically regulated. Here we show that sumoylation of NPR1 by SUMO3 activates defense gene expression by switching NPR1's association with the WRKY transcription repressors to TGA transcription activators. Sumoylation also triggers NPR1 degradation, rendering the immune induction transient. SUMO modification of NPR1 is inhibited by phosphorylation at Ser55/Ser59, which keeps NPR1 stable and quiescent. Thus, posttranslational modifications enable dynamic but tight and precise control of plant immune responses. PMID- 26269954 TI - Inhibition of Dectin-1 Signaling Ameliorates Colitis by Inducing Lactobacillus Mediated Regulatory T Cell Expansion in the Intestine. AB - Dectin-1, the receptor for beta-glucans, protects the host against fungal infection; however, its role in intestinal immunity is incompletely understood. We found that Dectin-1-deficient (Clec7a(-/-)) mice were refractory to both dextran sodium sulfate (DSS)- and CD45RB(high)CD4(+) T cell-induced colitis, and that this resistance was associated with an increase in regulatory T (Treg) cells. The proportion of lactobacilli, especially Lactobacillus murinus, in the commensal microflora was increased in Clec7a(-/-) mouse colons, and accompanied by a decrease in antimicrobial peptides induced by Dectin-1 signaling. L. murinus colonization increased Treg cells in the colon. Oral administration of laminarin, a Dectin-1 antagonist, suppressed the development of DSS-colitis, associated with an increase of L. murinus and Treg cells. Human patients with inflammatory bowel disease were found to have a decreased proportion of closely related Lactobacillus species. These observations suggest that Dectin-1 regulates the homeostasis of intestinal immunity by controlling Treg cell differentiation through modification of microbiota. PMID- 26269955 TI - Pathogenic NLRP3 Inflammasome Activity during Candida Infection Is Negatively Regulated by IL-22 via Activation of NLRC4 and IL-1Ra. AB - Candida albicans is a well-tolerated resident of human mucosal tissues. This implies that host defense mechanisms cooperate to limit inflammation while controlling fungal burden. The cytokine IL-22 and inflammasomes are essential components of the mucosal responses to C. albicans. How these components cooperate to mediate the balance of inflammation and host defense is not explored. We find that NLRP3 inflammasome activation promotes neutrophil recruitment and inflammation during infection and that this activity is counteracted by IL-22. Mechanistically, IL-22 activated NLRC4 for sustained production of the IL-1 receptor antagonist IL-1Ra, which restrained NLRP3 activity. Symptomatic infection in mice and humans occurred under conditions of IL-1Ra deficiency and was rescued in mice by replacement therapy with the recombinant IL-1Ra anakinra. Thus, pathogenic inflammasome activity during Candida infection is negatively regulated by the IL-22/NLRC4/IL-1Ra axis. Our findings offer insights into the pathogenesis of C. albicans and suggest therapeutic avenues for candidiasis. PMID- 26269956 TI - A Toxoplasma gondii Gluconeogenic Enzyme Contributes to Robust Central Carbon Metabolism and Is Essential for Replication and Virulence. AB - The expression of gluconeogenic enzymes is typically repressed when glucose is available. The protozoan parasite Toxoplasma gondii utilizes host glucose to sustain high rates of intracellular replication. However, despite their preferential utilization of glucose, intracellular parasites constitutively express two isoforms of the gluconeogenic enzyme fructose 1,6-bisphosphatase (TgFBP1 and TgFBP2). The rationale for constitutive expression of FBPases in T. gondii remains unclear. We find that conditional knockdown of TgFBP2 results in complete loss of intracellular growth in vitro under glucose-replete conditions and loss of acute virulence in mice. TgFBP2 deficiency was rescued by expression of catalytically active FBPase and was associated with altered glycolytic and mitochondrial TCA cycle fluxes, as well as dysregulation of glycolipid, amylopectin, and fatty acid biosynthesis. Futile cycling between gluconeogenic and glycolytic enzymes may constitute a regulatory mechanism that allows T. gondii to rapidly adapt to changes in nutrient availability in different host cells. PMID- 26269958 TI - Screening for Fabry disease in left ventricular hypertrophy: documentation of a novel mutation. AB - BACKGROUND: Fabry disease is a lysosomal storage disease caused by enzyme alpha galactosidase A deficiency as a result of mutations in the GLA gene. Cardiac involvement is characterized by progressive left ventricular hypertrophy. OBJECTIVE: To estimate the prevalence of Fabry disease in a population with left ventricular hypertrophy. METHODS: The patients were assessed for the presence of left ventricular hypertrophy defined as a left ventricular mass index >= 96 g/m2 for women or >= 116 g/m2 for men. Severe aortic stenosis and arterial hypertension with mild left ventricular hypertrophy were exclusion criteria. All patients included were assessed for enzyme alpha-galactosidase A activity using dry spot testing. Genetic study was performed whenever the enzyme activity was decreased. RESULTS: A total of 47 patients with a mean left ventricular mass index of 141.1 g/m2 (+/- 28.5; 99.2 to 228.5 g/m2] were included. Most of the patients were females (51.1%). Nine (19.1%) showed decreased alpha-galactosidase A activity, but only one positive genetic test - [GLA] c.785G>T; p.W262L (exon 5), a mutation not previously described in the literature. This clinical investigation was able to establish the association between the mutation and the clinical presentation. CONCLUSION: In a population of patients with left ventricular hypertrophy, we documented a Fabry disease prevalence of 2.1%. This novel case was defined in the sequence of a mutation of unknown meaning in the GLA gene with further pathogenicity study. Thus, this study permitted the definition of a novel causal mutation for Fabry disease - [GLA] c.785G>T; p.W262L (exon 5). PMID- 26269962 TI - Carbon Dots: A Unique Fluorescent Cocktail of Polycyclic Aromatic Hydrocarbons. AB - Carbon dots (CDs) have attracted rapidly growing interest in recent years due to their unique and tunable optical properties, the low cost of fabrication, and their widespread uses. However, due to the complex structure of CDs, both the molecular ingredients and the intrinsic mechanisms governing photoluminescence of CDs are poorly understood. Among other features, a large Stokes shift of over 100 nm and a photoluminescence spectrally dependent on the excitation wavelength have so far not been adequately explained. In this Letter we investigate CDs and develop a model system to mimic their optical properties. This system comprised three types of polycyclic aromatic hydrocarbon (PAH) molecules with fine-tuned concentrations embedded in a polymer matrix. The model suggests that the Stokes shift in CDs is due to the self-trapping of an exciton in the PAH network. The width and the excitation dependence of the emission comes from a selective excitation of PAHs with slightly different energy gaps and from energy transfer between them. These insights will help to tailor the optical properties of CDs and help their implementation into applications, e.g., light-emitting devices and biomarkers. This could also lead to "artificial" tunable carbon dots by locally modifying the composition and consequently the optical properties of composite PAH films. PMID- 26269963 TI - Structural Characterisation of Complex Layered Double Hydroxides and TGA-GC-MS Study on Thermal Response and Carbonate Contamination in Nitrate- and Organic Exchanged Hydrotalcites. AB - Layered double hydroxides (LDHs) are versatile materials used for intercalating bioactive molecules in the fields of pharmaceuticals, nutraceuticals and cosmetics, with the purpose of protecting them from degradation, enhancing their water solubility to increase bioavailability and improving their pharmacokinetic properties and formulation stability. Moreover, LDHs are used in various technological applications to improve stability and processability. The crystal chemistry of hydrotalcite-like compounds was investigated by X-ray powder diffraction (XRPD), automated electron diffraction tomography (ADT) and thermogravimetric analysis (TGA)-GC-MS to shed light on the mechanisms involved in ion exchange and absorption of contaminants, mainly carbonate anions. For the first time, ADT allowed a structural model of LDH_NO3 to be obtained from experiment, shedding light on the conformation of nitrate inside LDH and on the loss of crystallinity due to the layer morphology. The ADT analysis of a hybrid LDH sample (LDH_EUS) clearly revealed an increase in defectivity in this material. XRPD demonstrated that the presence of carbonate can influence the intercalation of organic molecules into LDH, since CO3 -contaminated samples tend to adopt d spacings that are approximate multiples of the d spacing of LDH_CO3 . TGA-GC-MS allowed intercalated and surface- adsorbed organic molecules to be distinguished and quantified, the presence and amount of carbonate to be confirmed, especially at low concentrations (<2 wt %), and the different types and strengths of adsorption to be classified with respect to the temperature of elimination. PMID- 26269957 TI - RIP3 Regulates Autophagy and Promotes Coxsackievirus B3 Infection of Intestinal Epithelial Cells. AB - Receptor interacting protein kinase-3 (RIP3) is an essential kinase for necroptotic cell death signaling and has been implicated in antiviral cell death signaling upon DNA virus infection. Here, we performed high-throughput RNAi screening and identified RIP3 as a positive regulator of coxsackievirus B3 (CVB) replication in intestinal epithelial cells (IECs). RIP3 regulates autophagy, a process utilized by CVB for viral replication factory assembly, and depletion of RIP3 inhibits autophagic flux and leads to the accumulation of autophagosomes and amphisomes. Additionally, later in infection, RIP3 is cleaved by the CVB-encoded cysteine protease 3C(pro), which serves to abrogate RIP3-mediated necrotic signaling and induce a nonnecrotic form of cell death. Taken together, our results show that temporal targeting of RIP3 allows CVB to benefit from its roles in regulating autophagy while inhibiting the induction of necroptotic cell death. PMID- 26269965 TI - Application of Serological and DNA Methods for the Identification of Urine Specimen Donors. AB - Recent implementation of urine drug-screening policies in the workplace has resulted in an increase in the submission of substituted urine specimens. Donor verification of urine specimens often becomes necessary when the origin of a specimen is in question or when a positive drug test is contested. Methods reported for the identification of the urine donor include the analysis of blood group antigenic substances (ABH and Lewis systems), polymorphic proteins (group specific component, haptoglobin, and orosomucoid), and deoxyribonucleic acid (DNA). Since the concentrations of the antigenic substances and polymorphic proteins in urine are typically low, most serological procedures adapt a concentration step enhancing the presence of these substances in the resulting residue by a factor ranging from 100 to 3,000. Conventional (and a two dimensional) absorption-inhibition and electrophoresis procedures can then be applied to characterize the antigenic substances and polymorphic proteins. Recently developed DNA methodologies have also evolved to help characterize urine specimens and often provide more informative data than those derived from conventional serological approaches. As of this date, the unique nature of urine as the source of genetic markers has not yet been thoroughly explored and understood. Also, many related procedures and statistical data have yet to be empirically established. This state-of-the-art technology cannot yet "fingerprint" a urine specimen at this date. A limited number of investigations do indicate, however, that the combined use of serological and DNA approaches can provide valuable information helping to resolve the donorship issues that are frequently contested in drug urinalysis-related legal proceedings. PMID- 26269964 TI - Effects of Trait Self-Control on Response Conflict About Healthy and Unhealthy Food. AB - Self-control leads to positive life outcomes, but it is poorly understood. While previous research has focused on self-control failure, self-control success remains unexplored. The current studies aim to shed more light on the mechanisms of self-control by focusing on the resolution of response conflict as a key component in self-control success. Trait self-control was measured, and participants reported on the magnitude of response conflict they experienced about healthy and unhealthy foods in Study 1 (N = 146; Mage = 33.03; 59 females, 83 males, 4 unknown). The response conflict process was assessed in Study 2 (N = 118; Mage = 21.45; 68 females, 41 males, 9 unknown). Outcomes showed that self reported evaluative response conflict about food items was smaller for people high in trait self-control. Study 2 revealed that higher trait self-control predicted faster resolution of self-control conflict, and an earlier peak of the response conflict. Taken together, these results provide insight into what makes people with high trait self-control successful, namely, how they handle response conflict. Implications for self-control theories and future directions are discussed. PMID- 26269966 TI - Genetic Polymorphisms of Human Parotid Saliva and Their Application to Forensic Science. AB - Human saliva is one of the valuable resources for the identification of genetic markers. A number of polymorphisms are found in salivary proteins and enzymes. They could provide the important information for genetic studies and forensic science. Polymorphic proteins in saliva show very unique composition of amino acids, which are named proline-rich proteins (PRPs). Proline-rich proteins have some biochemical and immunological similarities and linkage has been shown to occur among them. Recent deoxyribonucleic acid (DNA) analysis suggests that PRP genes have to be reconsidered on the gene structure. This review includes the polymorphisms of salivary proteins and enzymes and their application for human genetics and forensic science. Recent DNA studies that suggest the reorganization of the loci controlling the production of PRPs are also discussed. PMID- 26269967 TI - A Historical Review of the Characterization of Blood and Secretion Stains in the Forensic Science Laboratory Part One: Bloodstains. AB - Laboratory tests were established during the latter part of the 19th century and the beginning of the 20th century that determined whether or not a stain was blood and, if so, from which species it originated. A few years after the discovery of the ABO blood groups in 1900, it was possible to detect these groups in bloodstains using the absorption-inhibition (A/I) technique. However, in the 1960s a new technique emerged that was more sensitive and quicker than A/I - the absorbtion-elution (A/E) method. Furthermore, it could be adapted to grouping semen and saliva stains. The biochemical technique of electrophoresis allowed the study of polymorphic forms of serum proteins and red cell enzymes in bloodstains. By 1980 it was theoretically possible to type a bloodstain in at least 16 different blood group systems. Even if a smaller number of these systems was identified in a stain, often very high levels of discrimination were achieved. Fewer blood grouping systems were applicable to secretion stains. The latest development of DNA profiling, however, allows the determination of the source of a stain from blood or semen with a degree of certainty never before attained. Technical success has nevertheless brought problems both for the laboratory and the courts, some of which are addressed here. PMID- 26269968 TI - Urinary Metabolites of Anabolic Steroids. AB - Anabolic steroids are abused for performance enhancement by athletes, and for appearance alteration by others. Urine drug testing is an effective deterrent in reducing their abuse. We have reviewed the current status of published information on the urinary metabolites (neutral fraction) of 17 anabolic steroids. The steroids are separated into five groups based on their structures: 17alpha-methyl steroids, 19-nor steroids, steroids with A-ring modifications, steroids with an extra ring, and steroids with B-ring and C-ring modifications. Common metabolic pathways are noted and summarized. PMID- 26269969 TI - Acute Macular Neuroretinopathy in Dengue Fever: Short-term Prospectively Followed Up Case Series. AB - IMPORTANCE: The incidence of dengue fever (DF) increases every year. Macular complications of patients with DF may be more common than many ophthalmologists realize. During a DF outbreak in South China in 2014, we observed acute macular neuroretinopathy associated with DF. OBSERVATIONS: Among 9 patients (17 eyes) with maculopathy post-DF, 5 patients (55.6%) (9 eyes) manifesting acute macular neuroretinopathy were recruited from August 1, 2014, to September 30, 2014, with a 6-month ophthalmic follow-up. Infrared reflectance imaging demonstrated localized areas of hyporeflection in the macula. Spectral-domain (SD) optical coherence tomography (OCT) scanning through these areas revealed hyperreflection in the photoreceptor layer and disruption of its normal reflective structures. Subsequent SD-OCT demonstrated that the hyperreflection of the photoreceptor layer regressed gradually, followed by thinning of the outer nuclear layer. The external limiting membrane and ellipsoid zone became continuous; however, the interdigitation zone was not restored. The scotomas persisted in all 5 patients (9 eyes) by the last visit. All 5 patients (9 eyes) in this case series were complicated with classic dengue maculopathy signs, such as intraretinal hemorrhage and exudation, which were completely resolved during the follow-up. CONCLUSIONS AND RELEVANCE: These data suggest that acute macular neuroretinopathy is a major manifestation of dengue maculopathy, with persistent scotomas through at least 6 months. PMID- 26269970 TI - Ab Initio Molecular Dynamics Calculations versus Quantum-State-Resolved Experiments on CHD3 + Pt(111): New Insights into a Prototypical Gas-Surface Reaction. AB - The dissociative chemisorption of methane on metal surfaces is of fundamental and practical interest, being a rate-limiting step in the steam reforming process. The reaction is best modeled with quantum dynamics calculations, but these are currently not guaranteed to produce accurate results because they rely on potential energy surfaces based on untested density functionals and on untested dynamical approximations. To help overcome these limitations, here we present for the first time statistically accurate reaction probabilities obtained with ab initio molecular dynamics (AIMD) for a polyatomic gas-phase molecule reacting with a metal surface. Using a general purpose density functional, the AIMD reaction probabilities are in semiquantitative agreement with new quantum-state resolved experiments on CHD3 + Pt(111). The comparison suggests the use of the sudden approximation for treating the rotations even though CHD3 has large rotational constants and yields an estimated reaction barrier of 0.9 eV for CH4 + Pt(111). PMID- 26269971 TI - Homogeneous Emission Line Broadening in the Organo Lead Halide Perovskite CH3NH3PbI3-xClx. AB - The organic-inorganic hybrid perovskites methylammonium lead iodide (CH3NH3PbI3) and the partially chlorine-substituted mixed halide CH3NH3PbI3-xClx emit strong and broad photoluminescence (PL) around their band gap energy of ~1.6 eV. However, the nature of the radiative decay channels behind the observed emission and, in particular, the spectral broadening mechanisms are still unclear. Here we investigate these processes for high-quality vapor-deposited films of CH3NH3PbI3 xClx using time- and excitation-energy dependent photoluminescence spectroscopy. We show that the PL spectrum is homogenously broadened with a line width of 103 meV most likely as a consequence of phonon coupling effects. Further analysis reveals that defects or trap states play a minor role in radiative decay channels. In terms of possible lasing applications, the emission spectrum of the perovskite is sufficiently broad to have potential for amplification of light pulses below 100 fs pulse duration. PMID- 26269972 TI - Branching Ratio between Proton Transfer and Electron Transfer Channels of a Bidirectional Proton-Coupled Electron Transfer. AB - Rigorous quantum dynamical study of concerted proton-coupled electron transfer (PCET) on the time scale of a few femtoseconds (fs) has been rarely reported. Herein, a time-dependent quantum wavepacket propagation method was applied to the dynamics of the charge-transfer excited electronic state of FHCl corresponding to F(+)HCl(-). The dynamics corresponds to a bidirectional PCET with two dissociation channels: the electron transfer (ET, generating FH+Cl) and proton transfer (PT, generating F+HCl) paths. The calculated branching ratio (Cl/F), 0.78, implies a surprising fact: PT prevails over ET. A detailed analysis of the proton movement and electron readjustment suggests that the proton movement starts ~3 fs earlier than the electron movement, and the electron readjustment is triggered by the initial movement of the proton. The branching ratio drastically inverts to 1.24 because of a reduced nonadiabatic effect in the isotope substituted system, FDCl. PMID- 26269973 TI - The Role of Intrinsic Defects in Methylammonium Lead Iodide Perovskite. AB - One of the major merits of CH3NH3PbI3 perovskite as an efficient absorber material for the photovoltaic cell is its long carrier lifetime. We investigate the role of the intrinsic defects of CH3NH3PbI3 on its outstanding photovoltaic properties using density-functional studies. Two types of defects are of interest, i.e., Schottky defects and Frenkel defects. Schottky defects, such as PbI2 and CH3NH3I vacancy, do not make a trap state, which can reduce carrier lifetime. Elemental defects like Pb, I, and CH3NH3 vacancies derived from Frenkel defects act as dopants, which explains the unintentional doping of methylammonium lead halides (MALHs). The absence of gap states from intrinsic defects of MALHs can be ascribed to the ionic bonding from organic-inorganic hybridization. These results explain why the perovskite MALHs can be an efficient semiconductor, even when grown using simple solution processes. It also suggests that the n-/p-type can be efficiently manipulated by controlling growth processes. PMID- 26269974 TI - Identifying Descriptors for Solvent Stability in Nonaqueous Li-O2 Batteries. AB - One crucial challenge in developing rechargeable Li-O2 batteries is to identify a stable solvent that is resistant to decomposition in the electrochemical environment of Li2O2. We attempt to identify descriptors that could be used to test for solvent stability. We build on the recent quantitative experimental results on oxygen consumption and release during discharge and charge respectively. We limit our focus to understanding trends in oxidative stability of solvents and based on a systematic treatment of the electrochemical environment of Li2O2, we propose that, to a first approximation, the highest occupied molecular orbital (HOMO) level could be a good descriptor. We demonstrate that this descriptor correlates well with the experimentally measured degree of rechargeability. We utilize this descriptor to screen a large number of solvents and identify several solvents that could enhance the rechargeability of nonaqueous Li-O2 batteries. We provide a comprehensive compilation of available computational and experimental data of several key solvent parameters that we believe will be the genesis for an 'electrolyte genome'. PMID- 26269975 TI - Direct Visualization of Electronic Asymmetry within a Phenyl-Linked Porphyrin Dimer. AB - Asymmetric electronic structures within a single molecule have been investigated by scanning tunneling microscopy and spectroscopy. Inside of a phenyl-linked porphyrin dimer, the asymmetric electronic structures are achieved by the incorporation of a cobalt ion in one porphyrin moiety. We find that a p-n junction between two pi-conjugated segments is formed within the porphyrin dimer. The understanding of the local electronic structures of the intramolecular p-n junction should represent a fundamental step to realizing single molecular devices. PMID- 26269976 TI - A DFT Study of Linear Gold-Thiolate Superclusters Absorbing in the Therapeutic NIR Window. AB - A series of linear clusters up to an aspect ratio of 1:6, formed as multimers of smaller clusters with an icosahedral Au13(5+) core having an eight-electron superatom configuration, are computationally predicted to have a greatly enhanced size-dependent absorption in the near-infrared (NIR) region extending to the biologically important NIR window. A novel structural model is presented for the previously isolated thiol-stabilized Au54(SR)30 cluster, where the metal core is formed as a heterodimer of the cores of the known Au25(SR)18(-/0) and Au38(SR)24 clusters. PMID- 26269978 TI - Thermal Signatures of Plasmonic Fano Interferences: Toward the Achievement of Nanolocalized Temperature Manipulation. AB - A consequence of thermal diffusion is that heat, even when applied to a localized region of space, has the tendency to produce a temperature change that is spatially uniform throughout a material with a thermal conductivity that is much larger than that of its environment. This implies that the degree of spatial correlation between the heat power supplied and the temperature change that it induces is likely to be small. Here, we show, via theory and simulation, that through a Fano interference, temperature changes can be both localized and controllably directed within certain plasmon-supporting metal nanoparticle assemblies. This occurs even when all particles are composed of the same material and contained within the same diffraction-limited spot. These anomalous thermal properties are compared and contrasted across three different nanosystems, the coupled nanorod-antenna, the heterorod dimer, and the nanocube on a substrate, known to support both spatial and spectral Fano interferences. We conclude that the presence of a Fano resonance is not sufficient by itself to induce a controllably nanolocalized temperature change. However, when present in a nanosystem of the right composition and morphology, temperature changes can be manipulated with nanoscale precision, despite thermal diffusion. PMID- 26269977 TI - Importance of Polaronic Effects for Charge Transport in CdSe Quantum Dot Solids. AB - We developed an accurate model accounting for electron-phonon interaction in colloidal quantum dot supercrystals that allowed us to identify the nature of charge carriers and the electrical transport regime. We find that in experimentally analyzed CdSe nanocrystal solids, the electron-phonon interaction is sufficiently strong that small polarons localized to single dots are formed. Charge-carrier transport occurs by small polaron hopping between the dots, with mobility that decreases with increasing temperature. While such a temperature dependence of mobility is usually considered as a proof of band transport, we show that the same type of dependence occurs in the system where transport is dominated by small polaron hopping. PMID- 26269979 TI - Electron- and Energy-Transfer Processes in a Photocatalytic System Based on an Ir(III)-Photosensitizer and an Iron Catalyst. AB - The reaction pathways of bis-(2-phenylpyridinato-)(2,2' bipyridine)iridium(III)hexafluorophosphate [Ir(ppy)2(bpy)]PF6 within a photocatalytic water reduction system for hydrogen generation based on an iron catalyst were investigated by employing time-resolved photoluminescence spectroscopy and time-dependent density functional theory. Electron transfer (ET) from the sacrificial reagent to the photoexcited Ir complex has a surprisingly low probability of 0.4% per collision. Hence, this step limits the efficiency of the overall system. The calculations show that ET takes place only for specific encounter geometries. At the same time, the presence of the iron-catalyst represents an energy loss channel due to a triplet-triplet energy transfer of Dexter type. This loss channel is kept small by the employed concentration ratios, thus favoring the reductive ET necessary for the water reduction. The elucidated reaction mechanisms underline the further need to improve the sun light's energy pathway to the catalyst to increase the efficiency of the photocatalytic system. PMID- 26269980 TI - Understanding Atom Probe Tomography of Oxide-Supported Metal Nanoparticles by Correlation with Atomic-Resolution Electron Microscopy and Field Evaporation Simulation. AB - Oxide-supported metal nanoparticles are widely used in heterogeneous catalysis. The increasingly detailed design of such catalysts necessitates three-dimensional characterization with high spatial resolution and elemental selectivity. Laser assisted atom probe tomography (APT) is uniquely suited to the task but faces challenges with the evaporation of metal/insulator systems. Correlation of APT with aberration-corrected scanning transmission electron microscopy (STEM), for Au nanoparticles embedded in MgO, reveals preferential evaporation of the MgO and an inaccurate assessment of nanoparticle composition. Finite element field evaporation modeling is used to illustrate the evolution of the evaporation front. Nanoparticle composition is most accurately predicted when the MgO is treated as having a locally variable evaporation field, indicating the importance of considering laser-oxide interactions and the evaporation of various molecular oxide ions. These results demonstrate the viability of APT for analysis of oxide supported metal nanoparticles, highlighting the need for developing a theoretical framework for the evaporation of heterogeneous materials. PMID- 26269981 TI - Tailored Oxygen Framework of Li4Ti5O12 Nanorods for High-Power Li Ion Battery. AB - Here we designed the kinetically favored Li4Ti5O12 by modifying its crystal structure to improve intrinsic Li diffusivity for high power density. Our first principles calculations revealed that the substituted Na expanded the oxygen framework of Li4Ti5O12 and facilitated Li ion diffusion in Li4Ti5O12 through 3-D high-rate diffusion pathway secured by Na ions. Accordingly, we synthesized sodium-substituted Li4Ti5O12 nanorods having not only a morphological merit from 1-D nanostructure engineering but also sodium substitution-induced open framework to attain ultrafast Li diffusion. The new material exhibited an outstanding cycling stability and capacity retention even at 200 times higher current density (20 C) compared with the initial condition (0.1 C). PMID- 26269982 TI - Air-Exposure-Induced Gas-Molecule Incorporation into Spiro-MeOTAD Films. AB - Combined photoemission and charge-transport property studies of the organic hole transport material 2,2',7,7'-tetrakis(N,N-di-p-methoxyphenylamine)-9,9' spirobifluorene (spiro-MeOTAD) under air exposure and controlled environments of O2, H2O + N2, and N2 (1 atm and under dark conditions) reveal the incorporation of gas molecules causing a decrease in charge mobility. Ultraviolet photoelectron spectroscopy shows the Fermi level shifts toward the highest occupied molecular orbital of spiro-MeOTAD when exposed to air, O2, and H2O resembling p-type doping. However, no traces of oxidized spiro-MeOTAD(+) are observed by X-ray photoelectron spectroscopy (XPS) and UV-visible spectroscopy. The charge transport properties were investigated by fabricating organic field-effect transistors with the 10 nm active layer at the semiconductor-insulator interface exposed to different gases. The hole mobility decreases substantially upon exposure to air, O2, and H2O. In the case of N2, XPS reveals the incorporation of N2 molecules into the film, but the decrease in the hole mobility is much smaller. PMID- 26269983 TI - Electrostatic Domination of the Effect of Electron Correlation in Intermolecular Interactions. AB - The electron-electron correlation energy is negative, and attractive dispersion interactions are entirely a correlation effect; therefore, the contribution of correlation to intermolecular binding is commonly assumed to be negative, or binding in nature. However, there are many cases where the long-range correlation binding energy is positive, with certain geometries of the water dimer as a prominent example. Geometries with dipoles misaligned can also have an electrostatically dominated, though negative, long-range correlation binding. In either case, the interaction decays as R(-3). This has its origin in the systematic overestimation of dipole moments by Hartree-Fock theory, leading to a reduction in the calculated electrostatic attraction upon inclusion of correlation. Thus, energy decomposition analyses that include correlation but do not correct mean field electrostatic terms are suboptimal. Attenuated second order Moller-Plesset theory, which smoothly truncates long-range electron correlation effects to zero, can, paradoxically, have the correct long-range behavior for many intermolecular interactions. PMID- 26269984 TI - Coherent Oscillations in Chlorosome Elucidated by Two-Dimensional Electronic Spectroscopy. AB - Chlorosomes are the most efficient photosynthetic light-harvesting complexes found in nature and consist of many bacteriochlorophyll (BChl) molecules self assembled into supramolecular aggregates. Here we elucidate the presence and the origin of coherent oscillations in chlorosome at cryogenic temperature using 2D electronic spectroscopy. We observe coherent oscillations of multiple frequencies superimposed on the ultrafast amplitude decay of 2D spectra. Comparison of oscillatory features in the rephasing and nonrephasing 2D spectra suggests that an oscillation of 620 cm(-1) frequency arises from electronic coherence. However, this coherent oscillation can be enhanced by vibronic coupling with intermolecular vibrations of BChl aggregate, and thus it might originate from vibronic coherence rather than pure electronic coherence. Although the 620 cm(-1) oscillation dephases rapidly, the electronic (or vibronic) coherence may still take part in the initial step of energy transfer in chlorosome, which is comparably fast. PMID- 26269985 TI - Chemical Warfare Agent Surface Adsorption: Hydrogen Bonding of Sarin and Soman to Amorphous Silica. AB - Sarin and soman are warfare nerve agents that represent some of the most toxic compounds ever synthesized. The extreme risk in handling such molecules has, until now, precluded detailed research into the surface chemistry of agents. We have developed a surface science approach to explore the fundamental nature of hydrogen bonding forces between these agents and a hydroxylated surface. Infrared spectroscopy revealed that both agents adsorb to amorphous silica through the formation of surprisingly strong hydrogen-bonding interactions with primarily isolated silanol groups (SiOH). Comparisons with previous theoretical results reveal that this bonding occurs almost exclusively through the phosphoryl oxygen (P?O) of the agent. Temperature-programmed desorption experiments determined that the activation energy for hydrogen bond rupture and desorption of sarin and soman was 50 +/- 2 and 52 +/- 2 kJ/mol, respectively. Together with results from previous studies involving other phosphoryl-containing molecules, we have constructed a detailed understanding of the structure-function relationship for nerve agent hydrogen bonding at the gas-surface interface. PMID- 26269986 TI - Catalysis with Metal Nanoparticles Immobilized within the Pores of Metal-Organic Frameworks. AB - Metal-organic frameworks (MOFs) are highly ordered crystalline porous materials prepared by the self-assembly of metal ions and organic linkers having low density framework structures of diversified topologies with tunable pore sizes and exceptionally large surface areas. Other than outstanding gas/molecule storage properties, loading of metal nanoparticles (MNPs) into the pores of MOFs could afford heterogeneous catalysts having advantages of controlling the particle growth to a nanosize region, resulting in highly active sites and enhanced catalytic performances, and these entrapped MNPs within MOF pores could be accessed by reactants for chemical transformations. This is a rapidly developing research area, and this Perspective addresses current achievements and future challenges for diverse MOF-immobilized MNPs within their pores, focusing especially on their preparation, characterization, and application as heterogeneous catalysts. PMID- 26269987 TI - Thickness-Dependent Full-Color Emission Tunability in a Flexible Carbon Dot Ionogel. AB - Multicolor luminescent materials are of immense importance nowadays, while it still constitutes a challenge to achieve luminescence color tunability, transparency, and flexibility at the same time. Here we show how ultrasmall carbon dots (CDs) fluorescing strongly across the visible spectrum can be surface functionalized and incorporated into highly flexible hybrid materials by combination with ionic liquids within silica gel networks to form CD-ionogels with properties promising for fabrication of flexible displays and other optical technologies without the use of any toxic materials. We demonstrate how the emission from such hybrid materials can be tuned across a large range of the Commission Internationale de l'Enclairage (CIE) display gamut giving full-color performance. We highlight how the rich ladder of emissive states attributable to organic functional groups and CD surface functionalization supports a smooth sequential multiple self-absorption tuning mechanism to red shift continuously from blue emitting n-pi* transitions down through the lower energy states. PMID- 26269988 TI - High Photoluminescence Efficiency and Optically Pumped Lasing in Solution Processed Mixed Halide Perovskite Semiconductors. AB - The study of the photophysical properties of organic-metallic lead halide perovskites, which demonstrate excellent photovoltaic performance in devices with electron- and hole-accepting layers, helps to understand their charge photogeneration and recombination mechanism and unravels their potential for other optoelectronic applications. We report surprisingly high photoluminescence (PL) quantum efficiencies, up to 70%, in these solution-processed crystalline films. We find that photoexcitation in the pristine CH3NH3PbI3-xClx perovskite results in free charge carrier formation within 1 ps and that these free charge carriers undergo bimolecular recombination on time scales of 10s to 100s of ns. To exemplify the high luminescence yield of the CH3NH3PbI3-xClx perovskite, we construct and demonstrate the operation of an optically pumped vertical cavity laser comprising a layer of perovskite between a dielectric mirror and evaporated gold top mirrors. These long carrier lifetimes together with exceptionally high luminescence yield are unprecedented in such simply prepared inorganic semiconductors, and we note that these properties are ideally suited for photovoltaic diode operation. PMID- 26269989 TI - In Situ TEM Observations on the Sulfur-Assisted Catalytic Growth of Single-Wall Carbon Nanotubes. AB - The effect of sulfur on the catalytic nucleation and growth of single-wall carbon nanotubes (SWCNTs) from an iron catalyst was investigated in situ by transmission electron microscopy (TEM). The catalyst precursor of ferrocene and growth promoter of sulfur were selectively loaded inside of the hollow core of multiwall CNTs with open ends, which served as a nanoreactor powered by applying a voltage inside of the chamber of a TEM. It was found that a SWCNT nucleated and grew perpendicularly from a region of the catalyst nanoparticle surface, instead of the normal tangential growth that occurs with no sulfur addition. Our in situ TEM observation combined with CVD growth studies suggests that sulfur functions to promote the nucleation and growth of SWCNTs by forming inhomogeneous local active sites and modifying the interface bonding between catalysts and precipitated graphitic layers, so that carbon caps can be lifted off from the catalyst particle. PMID- 26269990 TI - Quantum Yield of Polariton Emission from Hybrid Light-Matter States. AB - The efficiency of light-matter strong coupling is tuned by precisely varying the spatial position of a thin layer of cyanine dye J-aggregates in Fabry-Perot microcavities, and their photophysical properties are determined. Placing the layer at the cavity field maximum affords an interaction energy (Rabi splitting) of 503 meV, a 62% increase over that observed if the aggregates are simply spread evenly through the cavity, placing the system in the ultrastrong coupling regime. The fluorescence quantum yield of the lowest polaritonic state P- integrated over k-space is found to be ~10(-2). The same value can be deduced from the 1.4 ps lifetime of P- measured by femtosecond transient absorption spectroscopy and the calculated radiative decay rate constant. Thus, the polariton decay is dominated by nonradiative processes, in contrast with what might be expected from the small effective mass of the polaritons. These findings provide a deeper understanding of hybrid light-molecule states and have implications for the modification of molecular and material properties by strong coupling. PMID- 26269991 TI - How Hydrogen Bonds Affect the Growth of Reverse Micelles around Coordinating Metal Ions. AB - Extensive research on hydrogen bonds (H-bonds) have illustrated their critical role in various biological, chemical and physical processes. Given that existing studies are predominantly performed in aqueous conditions, how H-bonds affect both the structure and function of aggregates in organic phase is poorly understood. Herein, we investigate the role of H-bonds on the hierarchical structure of an aggregating amphiphile-oil solution containing a coordinating metal complex by means of atomistic molecular dynamics simulations and X-ray techniques. For the first time, we show that H-bonds not only stabilize the metal complex in the hydrophobic environment by coordinating between the Eu(NO3)3 outer sphere and aggregating amphiphiles, but also affect the growth of such reverse micellar aggregates. The formation of swollen, elongated reverse micelles elevates the extraction of metal ions with increased H-bonds under acidic condition. These new insights into H-bonds are of broad interest to nanosynthesis and biological applications, in addition to metal ion separations. PMID- 26269992 TI - Photovoltaic Heterojunctions of Fullerenes with MoS2 and WS2 Monolayers. AB - First-principles calculations are performed to explore the geometry, bonding, and electronic structures of six ultrathin photovoltaic heterostructures consisting of pristine and B- or N-doped fullerenes and MoS2 or WS2 monolayers. The fullerenes prefer to be attached with a hexagon parallel to the monolayer, where B and N favor proximity to the monolayer. The main electronic properties of the subsystems stay intact, suggesting weak interfacial interaction. Both the C60/MoS2 and C60/WS2 systems show type-II band alignments. However, the built-in potential in the former case is too small to effectively drive electron-hole separation across the interface, whereas the latter system is predicted to show good photovoltaic performance. Unfortunately, B and N doping destroys the type-II band alignment on MoS2 and preserves it only in one spin channel on WS2, which is unsuitable for excitonic solar cells. Our results suggest that the C60/WS2 system is highly promising for excitonic solar cells. PMID- 26269993 TI - On the Controversial Nature of the 825 nm Exciton Band in the FMO Protein Complex. AB - The nature of the low-energy 825 nm band of the Fenna-Matthews-Olson (FMO) protein complex from Chlorobaculum tepidum at 5 K is discussed. It is shown, using hole-burning (HB) spectroscopy and excitonic calculations, that the 825 nm absorption band of the FMO trimer cannot be explained by a single electronic transition or overlap of electronic transitions of noninteracting pigments. To explain the shape of emission and nonresonant HB spectra, downward uncorrelated excitation energy transfer (EET) between trimer subunits should be taken into account. Modeling studies reveal the presence of three sub-bands within the 825 nm band, in agreement with nonresonant HB and emission spectra. We argue that after light induced coherences vanish, uncorrelated EET between the lowest exciton levels of each monomer takes place. HB induced spectral shifts provide a new insight on the energy landscape of the FMO protein. PMID- 26269994 TI - Rechargeable Aqueous Microdroplet. AB - Directional and controllable transportation of microdroplets is critical for emerging micro- and nanotechnology, in which the conventional mechanical energy generation is not applicable. This Letter shows that an aqueous microdroplet can be charged for controlled motion in electrostatic potential, which was created by differentiating pH, between two oil/water interfaces. The directional motion of the droplet, <100 MUm in diameter, was obtained with a constant velocity of ~1 mm/s. The force analysis showed that the droplet surface was charged and recharged oppositely by ion transfer through interfacial layers, without significant mass transfer. The charging and recharging cycles were recorded continuously with a single droplet over 100 times. The energy for motion was generated from pH neutralization, which is the simplest aqueous reaction. This is the first time that the phenomenon is reported. The phenomenon can be employed as an efficient and robust method to convert chemical to mechanical energy for miniaturized devices and microprocesses. PMID- 26269995 TI - Photochemical Dynamics of Ethylene Cation C2H4(.). AB - We present a theoretical study of the nonadiabatic effects in ethylene cation C2H4(+), the simplest pi radical cation, after photoexcitation to its three lowest doublet excited states. Two families of conical intersections are found, with minimum energy structures characterized by planar and twisted geometries. Ab initio multiple spawning dynamical calculations suggest that the competition between these relaxation pathways depends strongly on the initial excited state, with excited state lifetimes in the 30-60 fs range. Ultrafast decay via planar geometries deposits the molecule near a bridged minimum on the ground state, allowing prompt H migration events. The alternative pathway mediated by torsional motion induces important backspawned population transfer promoted by hindered rotations. The results allow us to revisit earlier vibrationally-mediated photodissociation experiments and shed light on the electronic relaxation dynamics of a prototypical radical cation subject to strong vibronic interactions. PMID- 26269996 TI - Deswelling and Electrolyte Dissipation in Free Diffusion of Charged PAMAM Dendrimers. AB - The diffusion coefficient of charged PAMAM dendrimers was measured by fluorescence correlation spectroscopy in aqueous solution at submicromolar concentrations. The solution pH was varied for conditions ranging from a fully charged to neutral charge dendrimer to infer about electrostatic swelling in the dilute regime. The diffusion coefficient of generation G4 increases by as much as 20% between high and low charge conditions due to the combined effects of polyelectrolyte deswelling and loss of electrolyte dissipation. By taking into account the electrolyte dissipation in the friction factor, we have found that the observed deswelling corresponds to a change of hydrodynamic radius between 7 13% for generation G4 and about 12% for generation G7. Simulations of molecular dynamics of dendrimer G4 show that counterion uptake by the dendrimer structure upon full protonation induces a 16% increase of its radius of gyration. The change in dendrimer size is slightly larger than that previously reported from neutron scattering techniques, thereby suggesting that electrostatic swelling is more pronounced at dilute dendrimer concentration and low ionic strength. It is confirmed that even higher generations, which have more congested molecular structures, can experience some degree of conformational change in response to a change of the dendrimer charge density. PMID- 26269997 TI - Light Management with Nanostructures for Optoelectronic Devices. AB - Light management is of paramount importance to improve the performance of optoelectronic devices including photodetectors, solar cells, and light-emitting diodes. Extensive studies have shown that the efficiency of these optoelectronic devices largely depends on the device structural design. In the case of solar cells, three-dimensional (3-D) nanostructures can remarkably improve device energy conversion efficiency via various light-trapping mechanisms, and a number of nanostructures were fabricated and exhibited tremendous potential for highly efficient photovoltaics. Meanwhile, these optical absorption enhancement schemes can benefit photodetectors by achieving higher quantum efficiency and photon extraction efficiency. On the other hand, low extraction efficiency of a photon from the emissive layer to outside often puts a constraint on the external quantum efficiency (EQE) of LEDs. In this regard, different designs of device configuration based on nanostructured materials such as nanoparticles and nanotextures were developed to improve the out-coupling efficiency of photons in LEDs under various frameworks such as waveguides, plasmonic theory, and so forth. In this Perspective, we aim to provide a comprehensive review of the recent progress of research on various light management nanostructures and their potency to improve performance of optoelectronic devices including photodetectors, solar cells, and LEDs. PMID- 26269998 TI - Management Strategies for the Nanoscale. PMID- 26269999 TI - Size and Structure Effects Controlling the Stability of the Liquid Organic Hydrogen Carrier Dodecahydro-N-ethylcarbazole during Dehydrogenation over Pt Model Catalysts. AB - Hydrogen can be stored conveniently using so-called liquid organic hydrogen carriers (LOHCs), for example, N-ethylcarbazole (NEC), which can be reversibly hydrogenated to dodecahydro-N-ethylcarbazole (H12-NEC). In this study, we focus on the dealkylation of H12-NEC, an undesired side reaction, which competes with dehydrogenation. The structural sensivity of dealkylation was studied by high resolution X-ray photoelectron spectroscopy (HR-XPS) on Al2O3-supported Pt model catalysts and Pt(111) single crystals. We show that the morphology of the Pt deposit strongly influences LOHC degradation via C-N bond breakage. On smaller, defect-rich Pt particles, the onset of dealkylation is shifted by 90 K to lower temperatures as compared to large, well-shaped particles and well-ordered Pt(111). We attribute these effects to a reduced activation barrier for C-N bond breakage at low-coordinated Pt sites, which are abundant on small Pt aggregates but are rare on large particles and single crystal surfaces. PMID- 26270000 TI - What are the options for non-small-cell lung cancer patients post second-line therapy? PMID- 26270001 TI - Online Education for Improving Communication and Documentation of Dietary Supplements Among Health Professionals Practicing in a Hospital Setting. AB - BACKGROUND: Little is known about the feasibility of online education in improving communication and documentation of dietary supplements (DS) among clinicians. METHODS: This prospective educational study included clinicians at an urban teaching hospital. The curriculum included video streams, didactics, and interactive case presentations to discuss (1) DS safety and effectiveness, (2) cultural competency, (3) managing DS in a hospital setting, and (4) DS adverse events. Participants were surveyed, at baseline and after training, about DS knowledge, confidence, communication, and documentation practices. RESULTS: Thirty-nine of 61 (64%) recruited clinicians completed all four patient cases and post-tests. Most (82%) were women and 59% were physicians. The mean DS knowledge test score increased after the curriculum (p < 0.0001), and the clinician confidence score also increased (p < 0.0001). Most (82%) participants reported that curriculum changed their use of evidence-based resources (p = 0.01). There was a change in the indications for symptom management (p = 0.05) and gastrointestinal/digestive health issues (p = 0.03). There were statistically significant increases in the frequency of asking patients about DS use during discharge (p = 0.01), and 82% responded that the curriculum changed their DS documentation. CONCLUSION: An online curriculum is an effective tool for presenting DS education to clinicians with the goal of improving clinicians' knowledge, confidence, and documentation practices about DS. PMID- 26270002 TI - Point of View. PMID- 26270004 TI - Clinical disparity of haemolytic disease of the fetus and newborn in twin pregnancy. PMID- 26270005 TI - The Association Between Indwelling Arterial Catheters and Mortality in Hemodynamically Stable Patients With Respiratory Failure: A Propensity Score Analysis. AB - BACKGROUND: Indwelling arterial catheters (IACs) are used extensively in the ICU for hemodynamic monitoring and for blood gas analysis. IAC use also poses potentially serious risks, including bloodstream infections and vascular complications. The purpose of this study was to assess whether IAC use was associated with mortality in patients who are mechanically ventilated and do not require vasopressor support. METHODS: This study used the Multiparameter Intelligent Monitoring in Intensive Care II database, consisting of > 24,000 patients admitted to the Beth Israel Deaconess Medical Center ICU between 2001 and 2008. Patients requiring mechanical ventilation who did not require vasopressors or have a diagnosis of sepsis were identified, and the primary outcome was 28-day mortality. A model based on patient demographics, comorbidities, vital signs, and laboratory results was developed to estimate the propensity for IAC placement. Patients were then propensity matched, and McNemar test was used to evaluate the association of IAC with 28-day mortality. RESULTS: We identified 1,776 patients who were mechanically ventilated who met inclusion criteria. There were no differences in the covariates included in the final propensity model between the IAC and non-IAC propensity-matched groups. For the matched cohort, there was no difference in 28-day mortality between the IAC group and the non-IAC group (14.7% vs 15.2%; OR, 0.96; 95% CI, 0.62-1.47). CONCLUSIONS: In hemodynamically stable patients who are mechanically ventilated, the presence of an IAC is not associated with a difference in 28-day mortality. Validation in other datasets, as well as further analyses in other subgroups, is warranted. PMID- 26270006 TI - Capillarity-driven blood plasma separation on paper-based devices. AB - We demonstrate capillarity-driven plasma separation from whole blood on simple paper-based H-channels. This methodology, unlike other reported techniques, does not necessitate elaborate and complex instrumentation, and the usage of expensive consumables. We believe that this technique will be ideally suited to be implemented in rapid and portable blood diagnostic devices designed to be operative at locations with limited resources. PMID- 26270008 TI - Preoperative statin therapy for patients undergoing cardiac surgery. AB - BACKGROUND: Patients referred to cardiac surgery for cardiovascular disease are at significant risk for the development of major postoperative adverse events despite significant advances in surgical techniques and perioperative care. Statins (5-hydroxy-3-methylglutaryl-co-enzyme A (HMG-CoA) reductase inhibitors) have gained a pivotal role in the primary and secondary prevention of coronary artery disease and are thought to improve perioperative outcomes in patients undergoing cardiac surgery. This review is an updated version of a review that was first published in 2012. OBJECTIVES: To determine the effectiveness of preoperative statin therapy in patients undergoing cardiac surgery. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 11), MEDLINE (1950 to November 2013 Week 3), EMBASE (1980 to 3 December 2013 (Week 48)) and the metaRegister of Controlled Trials. Additionally, we searched ongoing trials through the National Research Register, the ClinicalTrials.gov registry and grey literature. We screened online conference indices from relevant scientific meetings (2006 to 2014) to look for eligible trials. We applied no language restrictions. SELECTION CRITERIA: All randomised controlled trials comparing any statin treatment before cardiac surgery, for any given duration and dose, versus no preoperative statin therapy (standard of care) or placebo. DATA COLLECTION AND ANALYSIS: Two review authors evaluated trial quality and extracted data from titles and abstracts identified by electronic database searches according to predefined criteria. Accordingly, we retrieved full-text articles of potentially relevant studies that met the inclusion criteria to assess definitive eligibility for inclusion. We reported effect measures as odds ratios (ORs) or weighted mean differences (WMDs) with 95% confidence intervals (95% CIs). MAIN RESULTS: We identified 17 randomised controlled studies including a total of 2138 participants undergoing on-pump or off-pump cardiac surgical procedures, and added to this review six studies with 1154 additional participants. Pooled analysis showed that statin treatment before surgery reduced the incidence of postoperative atrial fibrillation (AF) (OR 0.54, 95% CI 0.43 to 0.67; P value < 0.01; 12 studies, 1765 participants) but failed to influence short-term mortality (OR 1.80, 95% CI 0.38 to 8.54; P value = 0.46; two studies, 300 participants) or postoperative stroke (OR 0.70, 95% CI 0.14 to 3.63; P value = 0.67; two studies, 264 participants). In addition, statin therapy was associated with a shorter stay for patients on the intensive care unit (ICU) (WMD -3.19 hours, 95% CI -5.41 to -0.98; nine studies, 721 participants) and in the hospital (WMD -0.48 days, 95% CI -0.78 to -0.19; 11 studies, 1137 participants) when significant heterogeneity was observed. Results showed no reduction in myocardial infarction (OR 0.48, 95% CI 0.21 to 1.13; seven studies, 901 participants) or renal failure (OR 0.57, 95% CI 0.30 to 1.10; five studies, 467 participants) and were not affected by subgroup analysis. Trials investigating this safety endpoint reported no major or minor perioperative side effects of statins. AUTHORS' CONCLUSIONS: Preoperative statin therapy reduces the odds of postoperative atrial fibrillation (AF) and shortens the patient's stay on the ICU and in the hospital. Statin pretreatment had no influence on perioperative mortality, stroke, myocardial infarction or renal failure, but only two of all included studies assessed mortality. As analysed studies included mainly individuals undergoing myocardial revascularisation, results cannot be extrapolated to patients undergoing other cardiac procedures such as heart valve or aortic surgery. PMID- 26270009 TI - Cataract Surgery Outcomes From a Resident Training in a Low-Resource Setting in the Pacific. AB - PURPOSE: The aim of the study was to assess the overall quality of the cataract surgeries performed by a single resident during training in a core surgical competency in a low-resource environment. DESIGN: This was a retrospective cohort review of cataract surgeries performed by a single surgeon. METHODS: A retrospective chart review of all consecutive cases of cataract surgery, in patients older than age 20, performed by 1 resident during the residency period was undertaken. The low-resource residency training program was based in Suva, Fiji, and provided outreach services to other Pacific Islands. The main outcome measures were visual outcomes and sentinel complications in terms of World Health Organization recommendations and reports from high- and low-resource settings that were used as quality benchmarks. RESULTS: Complete data were available for 95% (670) of cataract surgeries. Five hundred eighty-nine patients (87.9%) had preoperative vision worse than 6/60. Three hundred eighty-seven surgeries (53.6%) were performed on outreach. Five hundred eighty-three (87%) achieved final postoperative best-corrected visual acuity of 6/18 or greater. The overall sentinel complication rate was 4% (26) and comprised posterior capsule rupture 2.7% (18), vitreous loss 1% (7), and endophthalmitis 0.15% (1). CONCLUSIONS: Visual outcomes and sentinel complication rates were comparable not only with World Health Organization recommendations but also with other low- and high resource environment training programs. PMID- 26270010 TI - Association between social capital and self-perception of health in Brazilian adults. AB - OBJECTIVE To investigate the association between social capital and social capital and self-perception of health based on examining the influence of health related behaviors as possible mediators of this relationship. METHODS A cross sectional study was used with 1,081 subjects, which is representative of the population of individuals aged 40 years or more in a medium-sized city in Southern Brazil. The subjects who perceived their health as fine, bad or very bad were considered to have a negative self-perception of their health. The social capital indicators were: number of friends, people from whom they could borrow money from when needed; the extent of trust in community members; whether or not members of the community helped each other; community safety; and extent of participation in community activities. The behaviors were: physical activity during leisure time, fruits and vegetable consumption, tobacco use and alcohol abuse. The odds ratios (OR) and confidence intervals (CI) 95% were calculated by binary logistic regression. The significance of mediation was verified using the Sobel test. RESULTS Following adjustment for demographic and clinical variables, subjects with fewer friends (OR = 1.39, 95%CI 1.08;1.80), those who perceived less frequently help from people in the neighborhood (OR = 1.30, 95%CI 1.01;1.68), who saw the violent neighborhood (OR = 1.33, 95%CI 1.01;1.74) and who had not participated in any community activity (OR = 1.39, 95%CI 1.07;1.80) had more negative self-perception of their health. Physical activity during leisure time was a significant mediator in the relationship between all social capital indicators (except for the borrowed money variable) and self-perceived health. Fruit and vegetable consumption was a significant mediator of the relationship between the extent of participation in community activities and self-perceived health. Tobacco use and alcohol abuse did not seem to have a mediating role in any relationship. CONCLUSIONS Lifestyle seems to only partially explain the relationship between social capital and self-perceived health. Among the investigated behaviors, physical activity during leisure time is what seems to have the most important role as a mediator of this relationship. PMID- 26270011 TI - Spatial analysis of the tuberculosis treatment dropout, Buenos Aires, Argentina. AB - OBJECTIVE Identify spatial distribution patterns of the proportion of nonadherence to tuberculosis treatment and its associated factors. METHODS We conducted an ecological study based on secondary and primary data from municipalities of the metropolitan area of Buenos Aires, Argentina. An exploratory analysis of the characteristics of the area and the distributions of the cases included in the sample (proportion of nonadherence) was also carried out along with a multifactor analysis by linear regression. The variables related to the characteristics of the population, residences and families were analyzed. RESULTS Areas with higher proportion of the population without social security benefits (p = 0.007) and of households with unsatisfied basic needs had a higher risk of nonadherence (p = 0.032). In addition, the proportion of nonadherence was higher in areas with the highest proportion of households with no public transportation within 300 meters (p = 0.070). CONCLUSIONS We found a risk area for the nonadherence to treatment characterized by a population living in poverty, with precarious jobs and difficult access to public transportation. PMID- 26270012 TI - Incidence and risk factors for intimate partner violence during the postpartum period. AB - OBJECTIVE To estimate the incidence and identify risk factors for intimate partner violence during postpartum. METHODS This prospective cohort study was conducted with women, aged between 18-49 years, enrolled in the Brazilian Family Health Strategy in Recife, Northeastern Brazil, between 2005 and 2006. Of the 1.057 women interviewed during pregnancy and postpartum, 539 women, who did not report violence before or during pregnancy, were evaluated. A theoretical conceptual framework was built with three levels of factors hierarchically ordered: women's and partners' sociodemografic and behavioral characteristics, and relationship dynamics. Incidence and risk factors of intimate partner violence were estimated by Poisson Regression. RESULTS The incidence of violence during postpartum was 9.3% (95%CI 7.0;12.0). Isolated psychological violence was the most common (4.3%; 95%CI 2.8;6.4). The overlapping of psychological with physical violence occurred at 3.3% (95%CI 2.0;5.3) and with physical and/or sexual in almost 2.0% (95%CI 0.8;3.0) of cases. The risk of partner violence during postpartum was increased for women with a low level of education (RR = 2.6; 95%CI 1.3;5.4), without own income (RR = 1.7; 95%CI 1.0;2.9) and those who perpetrated physical violence against their partner without being assaulted first (RR = 2.0; 95%CI 1.2;3.4), had a very controlling partner (RR = 2.5; 95%CI 1.1;5.8), and had frequent fights with their partner (RR = 1.7; 95%CI 1.0;2.9). CONCLUSIONS The high incidence of intimate partner violence during postpartum and its association with aspects of the relationship's quality between the couple, demonstrated the need for public policies that promote conflict mediation and enable forms of empowerment for women to address the cycle of violence. PMID- 26270013 TI - Validation of psychosocial scales for physical activity in university students. AB - OBJECTIVE Translate the Patient-centered Assessment and Counseling for Exercise questionnaire, adapt it cross-culturally and identify the psychometric properties of the psychosocial scales for physical activity in young university students. METHODS The Patient-centered Assessment and Counseling for Exercise questionnaire is made up of 39 items divided into constructs based on the social cognitive theory and the transtheoretical model. The analyzed constructs were, as follows: behavior change strategy (15 items), decision-making process (10), self-efficacy (6), support from family (4), and support from friends (4). The validation procedures were conceptual, semantic, operational, and functional equivalences, in addition to the equivalence of the items and of measurements. The conceptual, of items and semantic equivalences were performed by a specialized committee. During measurement equivalence, the instrument was applied to 717 university students. Exploratory factor analysis was used to verify the loading of each item, explained variance and internal consistency of the constructs. Reproducibility was measured by means of intraclass correlation coefficient. RESULTS The two translations were equivalent and back-translation was similar to the original version, with few adaptations. The layout, presentation order of the constructs and items from the original version were kept in the same form as the original instrument. The sample size was adequate and was evaluated by the Kaiser Meyer-Olkin test, with values between 0.72 and 0.91. The correlation matrix of the items presented r < 0.8 (p < 0.05). The factor loadings of the items from all the constructs were satisfactory (> 0.40), varying between 0.43 and 0.80, which explained between 45.4% and 59.0% of the variance. Internal consistency was satisfactory (alpha >= 0.70), with support from friends being 0.70 and 0.92 for self-efficacy. Most items (74.3%) presented values above 0.70 for the reproducibility test. CONCLUSIONS The validation process steps were considered satisfactory and adequate for applying to the population. PMID- 26270014 TI - Spatial distribution and socioeconomic context of tuberculosis in Rio de Janeiro, Brazil. AB - OBJECTIVE To analyze the spatial distribution of risk for tuberculosis and its socioeconomic determinants in the city of Rio de Janeiro, Brazil. METHODS An ecological study on the association between the mean incidence rate of tuberculosis from 2004 to 2006 and socioeconomic indicators of the Censo Demografico (Demographic Census) of 2000. The unit of analysis was the home district registered in the Sistema de Informacao de Agravos de Notificacao (Notifiable Diseases Information System) of Rio de Janeiro, Southeastern Brazil. The rates were standardized by sex and age group, and smoothed by the empirical Bayes method. Spatial autocorrelation was evaluated by Moran's I. Multiple linear regression models were studied and the appropriateness of incorporating the spatial component in modeling was evaluated. RESULTS We observed a higher risk of the disease in some neighborhoods of the port and north regions, as well as a high incidence in the slums of Rocinha and Vidigal, in the south region, and Cidade de Deus, in the west. The final model identified a positive association for the variables: percentage of permanent private households in which the head of the house earns three to five minimum wages; percentage of individual residents in the neighborhood; and percentage of people living in homes with more than two people per bedroom. CONCLUSIONS The spatial analysis identified areas of risk of tuberculosis incidence in the neighborhoods of the city of Rio de Janeiro and also found spatial dependence for the incidence of tuberculosis and some socioeconomic variables. However, the inclusion of the space component in the final model was not required during the modeling process. PMID- 26270015 TI - Socioeconomic inequalities and changes in oral health behaviors among Brazilian adolescents from 2009 to 2012. AB - OBJECTIVE To analyze oral health behaviors changes over time in Brazilian adolescents concerning maternal educational inequalities. METHODS Data from the Pesquisa Nacional de Saude do Escolar (Brazilian National School Health Survey) were analyzed. The sample was composed of 60,973 and 61,145 students from 26 Brazilian state capitals and the Federal District in 2009 and 2012, respectively. The analyzed factors were oral health behaviors (toothbrushing frequency, sweets consumption, soft drink consumption, and cigarette experimentation) and sociodemographics (age, sex, race, type of school and maternal schooling). Oral health behaviors and sociodemographic factors in the two years were compared (Rao Scott test) and relative and absolute measures of socioeconomic inequalities in health were estimated (slope index of inequality and relative concentration index), using maternal education as a socioeconomic indicator, expressed in number of years of study (> 11; 9-11; <= 8). RESULTS Results from 2012, when compared with those from 2009, for all maternal education categories, showed that the proportion of people with low toothbrushing frequency increased, and that consumption of sweets and soft drinks and cigarette experimentation decreased. In private schools, positive slope index of inequality and relative concentration index indicated higher soft drink consumption in 2012 and higher cigarette experimentation in both years among students who reported greater maternal schooling, with no significant change in inequalities. In public schools, negative slope index of inequality and relative concentration index indicated higher soft drink consumption among students who reported lower maternal schooling in both years, with no significant change overtime. The positive relative concentration index indicated inequality in 2009 for cigarette experimentation, with a higher prevalence among students who reported greater maternal schooling. There were no inequalities for toothbrushing frequency or sweets consumption. CONCLUSIONS There were changes in the prevalences of oral health behaviors during the analyzed period; however, these changes were not related to maternal education inequalities. PMID- 26270017 TI - Users' dissatisfaction with dental care: a population-based household study. AB - OBJECTIVE To examine whether demographic, socioeconomic conditions, oral health subjectivity and characterization of dental care are associated with users' dissatisfaction with such are. METHODS Cross-sectional study of 781 people who required dental care in Montes Claros, MG, Southeastern Brazil, in 2012, a city with of medium-sized population situated in the North of Minas Gerais. Household interviews were conducted to assess the users' dissatisfaction with dental care (dependent variable), demographic, socioeconomic conditions, oral health subjectivity and characterization of dental care (independent variables). Sample calculation was used for the finite population, with estimates made for proportions of dissatisfaction in 50.0% of the population, a 5.0% error margin, a non-response rate of 5.0% and a 2.0% design effect. Logistic regression was used, and the odds ratio was calculated with a 5% significance level and 95% confidence intervals. RESULTS Of the interviewed individuals, 9.0% (7.9%, with correction for design effect) were dissatisfied with the care provided. These were associated with lower educational level; negative self-assessment of oral health; perception that the care provider was unable to give dental care; negative evaluation of the way the patient was treated, the cleanliness of the rooms, based on the examination rooms and the toilets, and the size of the waiting and examination rooms. CONCLUSIONS The rate of dissatisfaction with dental care was low. This dissatisfaction was associated with socioeconomic conditions, subjectivity of oral health, skill of the health professionals relating to the professional-patient relationship and facility infrastructure. Educational interventions are suggested that aim at improving the quality of care among professionals by responsible agencies as is improving the infrastructure of the care units. PMID- 26270016 TI - Gender differences in the association between tooth loss and obesity among older adults in Brazil. AB - OBJECTIVE To analyze if differences according to gender exists in the association between tooth loss and obesity among older adults. METHODS We analyzed data on 1,704 older adults (60 years and over) from the baseline of a prospective cohort study conducted in Florianopolis, SC, Southern Brazil. Multivariable logistic regression models were used to assess the association between tooth loss and general and central obesity after adjustment for confounders (age, gender, skin color, educational attainment, income, smoking, physical activity, use of dentures, hypertension, and diabetes). Linear regressions were also assessed with body mass index and waist circumference as continuous outcomes. Interaction between gender and tooth loss was further assessed. RESULTS Overall mean body mass index was 28.0 kg/m2. Mean waist circumference was 96.8 cm for males and 92.6 cm for females. Increasing tooth loss was positively associated with increased body mass index and waist circumference after adjustment for confounders. Edentates had 1.4 (95%CI 1.1;1.9) times higher odds of being centrally obese than individuals with a higher number of teeth; however, the association lost significance after adjustment for confounders. In comparison with edentate males, edentate females presented a twofold higher adjusted prevalence of general and central obesity. In the joint effects model, edentate females had a 3.8 (95%CI 2.2;6.6) times higher odds to be centrally obese in comparison with males with more than 10 teeth present in both the arches. Similarly, females with less than 10 teeth in at least one arch had a 2.7 (95%CI 1.6;4.4) times higher odds ratio of having central obesity in comparison with males with more than 10 teeth present in both the arches. CONCLUSIONS Central obesity was more prevalent than general obesity among the older adults. We did not observe any association between general obesity and tooth loss. The association between central obesity and tooth loss depends on gender - females with tooth loss had greater probability of being obese. PMID- 26270018 TI - Free-trade agreements: challenges for global health. AB - In this study new free-trade agreements are discussed, which are based on the breaking down of tariff and technical barriers and normally exclude most of the poorest countries in the world. Considering the current context of economic globalization and its health impacts, seven controversial points of these treaties and their possible implications for global public health are presented, mainly regarding health equity and other health determinants. Finally, this research proposes a greater social and health professionals participation in the formulation and discussion of these treaties, and a deeper insertion of Brazil in this important international agenda. PMID- 26270019 TI - Impact of ultra-processed foods on micronutrient content in the Brazilian diet. AB - OBJECTIVE To evaluate the impact of consuming ultra-processed foods on the micronutrient content of the Brazilian population's diet. METHODS This cross sectional study was performed using data on individual food consumption from a module of the 2008-2009 Brazilian Household Budget Survey. A representative sample of the Brazilian population aged 10 years or over was assessed (n = 32,898). Food consumption data were collected through two 24-hour food records. Linear regression models were used to assess the association between the nutrient content of the diet and the quintiles of ultra-processed food consumption - crude and adjusted for family income per capita. RESULTS Mean daily energy intake per capita was 1,866 kcal, with 69.5% coming from natural or minimally processed foods, 9.0% from processed foods and 21.5% from ultra-processed foods. For sixteen out of the seventeen evaluated micronutrients, their content was lower in the fraction of the diet composed of ultra-processed foods compared with the fraction of the diet composed of natural or minimally processed foods. The content of 10 micronutrients in ultra-processed foods did not reach half the content level observed in the natural or minimally processed foods. The higher consumption of ultra-processed foods was inversely and significantly associated with the content of vitamins B12, vitamin D, vitamin E, niacin, pyridoxine, copper, iron, phosphorus, magnesium, selenium and zinc. The reverse situation was only observed for calcium, thiamin and riboflavin. CONCLUSIONS The findings of this study highlight that reducing the consumption of ultra-processed foods is a natural way to promote healthy eating in Brazil and, therefore, is in line with the recommendations made by the Guia Alimentar para a Populacao Brasileira (Dietary Guidelines for the Brazilian Population) to avoid these foods. PMID- 26270020 TI - Sugar-Based Polyamides: Self-Organization in Strong Polar Organic Solvents. AB - Periodic patterns resembling spirals were observed to form spontaneously upon unassisted cooling of d-glucaric acid- and d-galactaric acid-based polyamide solutions in N-methyl-N-morpholine oxide (NMMO) monohydrate. Similar observations were made in d-galactaric acid-based polyamide/ionic liquid (IL) solutions. The morphologies were investigated by optical, polarized light and confocal microscopy assays to reveal pattern details. Differential scanning calorimetry was used to monitor solution thermal behavior. Small- and wide-angle X-ray scattering data reflected the complex and heterogeneous nature of the self organized patterns. Factors such as concentration and temperature were found to influence spiral dimensions and geometry. The distance between rings followed a first-order exponential decay as a function of polymer concentration. Fourier Transform Infrared Microspectroscopy analysis of spirals pointed to H-bonding between the solvent and the pendant hydroxyl groups of the glucose units from the polymer backbone. Tests on self-organization into spirals of ketal-protected d galactaric acid polyamides in NMMO monohydrate confirmed the importance of the monosaccharide's pendant free hydroxyl groups on the formation of these patterns. Rheology performed on d-galactaric-based polyamides at high concentration in NMMO monohydrate solution revealed the optimum conditions necessary to process these materials as fibers by spinning. The self-organization of these sugar-based polyamides mimics certain biological materials. PMID- 26270021 TI - Decreased tacrolimus concentration following a temporal increase during interferon-free therapy with asunaprevir and daclatasvir in patients with recurrent hepatitis C after liver transplantation. PMID- 26270024 TI - In Memoriam: William J. Bair (1924-2015). PMID- 26270026 TI - Competitive Pseudopericyclic [3,3]- and [3,5]-Sigmatropic Rearrangements of Trichloroacetimidates. AB - The Woodward-Hoffmann rules predict whether concerted pericyclic reactions are allowed or forbidden based on the number of electrons involved and whether the cyclic orbital overlap involves suprafacial or antarafacial orbital overlap. Pseudopericyclic reactions constitute a third class of reactions in which orthogonal orbitals make them orbital symmetry allowed, regardless of the number of electrons involved in the reaction. Based on the recent report of eight centered ester rearrangements, it is predicted that the isoelectronic eight centered rearrangements of imidates would also be allowed. We now report that these rearrangements occur, and indeed, an eight-centered rearrangement is slightly favored in at least one case over the well-known six-centered Overman rearrangements, in a trichloroacetimidoylcyclohexadienone, a molecular system where both rearrangements are possible. PMID- 26270023 TI - Environmental Pollutant Ozone Causes Damage to Lung Surfactant Protein B (SP-B). AB - Lung surfactant protein B (SP-B) is an essential protein found in the surfactant fluid at the air-water interface of the lung. Exposure to the air pollutant ozone could potentially damage SP-B and lead to respiratory distress. We have studied two peptides, one consisting of the N-terminus of SP-B [SP-B(1-25)] and the other a construct of the N- and C-termini of SP-B [SP-B(1-25,63-78)], called SMB. Exposure to dilute levels of ozone (~2 ppm) of monolayers of each peptide at the air-water interface leads to a rapid reaction, which is evident from an increase in the surface tension. Fluorescence experiments revealed that this increase in surface tension is accompanied by a loss of fluorescence from the tryptophan residue at the interface. Neutron and X-ray reflectivity experiments show that, in contrast to suggestions in the literature, the peptides are not solubilized upon oxidation but rather remain at the interface with little change in their hydration. Analysis of the product material reveals that no cleavage of the peptides occurs, but a more hydrophobic product is slowly formed together with an increased level of oligomerization. We attributed this to partial unfolding of the peptides. Experiments conducted in the presence of phospholipids reveal that the presence of the lipids does not prevent oxidation of the peptides. Our results strongly suggest that exposure to low levels of ozone gas will damage SP B, leading to a change in its structure. The implication is that the oxidized protein will be impaired in its ability to interact at the air-water interface with negatively charged phosphoglycerol lipids, thus compromising what is thought to be its main biological function. PMID- 26270032 TI - Fast voxel-level dosimetry for (177)Lu labelled peptide treatments. AB - In peptide receptor radionuclide therapy (PRRT), voxel-level radiation absorbed dose calculations can be performed using several different methods. Each method has it strengths and weaknesses; however, Monte Carlo (MC) simulation is presently considered the most accurate method at providing absorbed dose distributions. Unfortunately MC simulation is time-consuming and often impractical to carry out in a clinical practice. In this work, a fast semi-Monte Carlo (sMC) absorbed dose calculation method for (177)Lu PRRT dosimetry is presented. The sMC method is based on a local electron absorption assumption and fast photon MC simulations. The sMC method is compared against full MC simulation code built on PENELOPE (vxlPen) using digital phantoms to assess the accuracy of these assumptions.Due to the local electron absorption assumption of sMC, the potential errors in cross-fire dose from electrons and photons emitted by (177)Lu were first evaluated using an ellipsoidal kidney model by comparing vxlPen and sMC. The photon cross-fire dose from background to kidney and kidney to background with varying kidney-to-background activity concentration ratios were calculated. In addition, kidney to kidney photon and electron cross-dose with different kidney to kidney distances were studied. Second, extended cardiac-torso (XCAT) phantoms were created with liver lesions and with realistic activity distributions and tissue densities. The XCAT phantoms were used to simulate SPECT projections and 3D activity distribution images were reconstructed using an OSEM algorithm. Image-based dose rate distributions were calculated using vxlPen and sMC. Total doses and dose rate volume histograms (DrVH) produced by the two methods were compared.The photon cross-fire dose from the kidney increased the background's absorbed dose by 5% or more up to 5.8 cm distance with 20 : 1 kidney to background activity concentration ratio. On the other hand, the photon cross fire dose from the background to the kidney volume was negligible. The vxlPen results showed that the cross fire dose between two similar kidney volumes relative to the source kidney's self-dose were 0.5% and 0.02% for photon and electrons, respectively, when source and target kidneys were modelled next to each other. The photon cross-dose decreased as function of distance, and electron doses were zero at distances larger than 4 mm. The difference between sMC and vxlPen kidney total doses in the XCAT phantom study was -0.4% while the electron dose DrVHs were identical between the methods. There was a systematic 5% difference in photon doses in soft tissue between the codes due to different simulations parameters. However, the photons produced only 4% of the kidney's total dose, thus the difference was not considered significant for total dose calculations.The comparison studies show that the absorbed doses calculated using the sMC differ only slightly from dedicated MC simulator results, while the dose estimates can be obtained in a fraction of the dedicated simulator's calculation time. Results imply that there is no need for electron MC simulation for (177)Lu absorption calculations with current SPECT systems. However, the photon cross fire dose should be taken into account in healthy tissues, which have a relatively low uptake especially in cases where there are high uptake volumes are nearby. PMID- 26270033 TI - Evaluation of a Consensus-Based Criterion Standard Definition of Trauma Center Need for Use in Field Triage Research. AB - Research on field triage of injured patients is limited by the lack of a widely used criterion standard for defining trauma center need. Injury Severity Score (ISS) >15 has been a commonly used outcome measure in research for determining trauma center need that has never been validated. A multidisciplinary team recently published a consensus-based criterion standard definition of trauma center need, but this measure has not yet been validated. The objective was to determine if the consensus-based criterion standard can be obtained by medical record review and compare patients identified as needing a trauma center by the consensus-based criterion standard vs. ISS >15. A subanalysis of data collected during a 2-year prospective cohort study of 4,528 adult trauma patients transported by EMS to a single trauma center was conducted. These data included ICD-9-CM codes, treatment times, and other patient care data. Presence of the consensus-based criterion standard was determined for each patient. ISS was calculated based on ICD-9-CM codes assigned for billing. The consensus-based criterion standard could be applied to 4,471 (98.7%) cases. ISS could be determined for 4,506 (99.5%) cases. Based on an ISS >15, 8.9% of cases were identified as needing a trauma center. Of those, only 48.2% met the consensus based criterion standard. Almost all patients that did not meet the consensus based criterion standard, but had an ISS >15 were diagnosed with chest (rib fractures (100/205 cases)/pneumothorax (57/205 cases), closed head (without surgical intervention 88/205 cases), vertebral (without spinal cord injury 45/205 cases), and/or extremity injuries (39/205 cases). There were 4,053 cases with an ISS <15. 5.0% of those with an ISS <15 met the consensus-based criterion standard with the majority requiring surgery (139/203 cases) or a blood transfusion (60/203 cases). The kappa coefficient of agreement for ISS and the consensus based criterion standard was 0.43. We determined that the consensus-based criterion standard could be identified through a medical record review. Use of the consensus-based criterion standard for field triage research will more accurately identify injured patients who need the resources of a trauma center when compared to ISS. PMID- 26270022 TI - Melanoma Risk and Survival among Organ Transplant Recipients. AB - Solid organ transplant recipients, who are medically immunosuppressed to prevent graft rejection, have increased melanoma risk, but risk factors and outcomes are incompletely documented. We evaluated melanoma incidence among 139,991 non Hispanic white transplants using linked US transplant-cancer registry data (1987 2010). We used standardized incidence ratios (SIRs) to compare incidence with the general population and incidence rate ratios (IRRs) from multivariable Poisson models to assess risk factors. Separately, we compared post-melanoma survival among transplant recipients (n=182) and non-recipients (n=131,358) using multivariable Cox models. Among transplant recipients, risk of invasive melanoma (n=519) was elevated (SIR=2.20, 95% CI 2.01-2.39), especially for regional stage tumors (SIR=4.11, 95% CI 3.27-5.09). Risk of localized tumors was stable over time after transplantation but higher with azathioprine maintenance therapy (IRR=1.35, 95% CI 1.03-1.77). Risk of regional/distant stage tumors peaked within 4 years following transplantation and increased with polyclonal antibody induction therapy (IRR=1.65, 95% CI 1.02-2.67). Melanoma-specific mortality was higher among transplant recipients than non-recipients (hazard ratio 2.98, 95% CI 2.26-3.93). Melanoma exhibits increased incidence and aggressive behavior under transplant-related immunosuppression. Some localized melanomas may result from azathioprine, which acts synergistically with UV radiation, whereas T-cell depleting induction therapies may promote late-stage tumors. Our findings support sun safety practices and skin screening for transplant recipients. PMID- 26270034 TI - Gas Phase Kinetics of 2,2,2-Trifluoroethylbutyrate with the Cl Atom: An Experimental and Theoretical Study. AB - The gas phase temperature dependent rate coefficients of Cl atoms with 2,2,2 trifluoroethylbutyrate, CH3CH2CH2C(O)OCH2CF3, were measured in the temperature range 268-343 K, at atmospheric pressures using the relative rate method, with ethyl acetate and ethane as reference compounds. The temperature dependent rate coefficients for the reaction of 2,2,2-TFEB + Cl were measured and were used to deduce the Arrhenius expression: k268-343K = [(4.42 +/- 0.01) * 10(-19)]T(2.6) exp{(1132 +/- 566)/T} cm(3) molecule(-1) s(-1). At 298 K, the rate coefficient for the title reaction is (4.54 +/- 2.87) * 10(-11) cm(3) molecule(-1) s(-1), which is in good agreement with a previously reported value at 298 K. To complement our experimental results over the studied temperature range, theoretical kinetic calculations were also performed for the title reaction using canonical variational transition state theory (CVT) with small curvature tunneling (SCT) corrections in combination with the CCSD(T)/cc-pVDZ//M062X/6 31+g(d,p) level of theory. The temperature dependent Arrhenius expression was obtained to be k(T) = (1.89 +/- 2.64) * 10(-21)T(3.4) exp{(1321 +/- 111)/T} cm(3) molecule(-1) s(-1). The branching ratios, atmospheric implications, and degradation mechanism of 2,2,2-trifluoroethylbutyrate, CH3CH2CH2C(O)OCH2CF3, were discussed in detail in this manuscript. PMID- 26270035 TI - Depression, Social Support, and Coping Styles among Pregnant Women after the Lushan Earthquake in Ya'an, China. AB - AIM: The aim of this study is to assess the depression of pregnant women in the aftermath of an earthquake, and to identify the social support that they obtained, their coping styles and socio-demographic factors associated with depression. METHODS: A total of 128 pregnant women from three hospitals in the epicenter area were recruited immediately after the Ya'an earthquake. Their depression was investigated using the Edinburgh Postnatal Depression Scale (EPDS) with a cutoff score of 14; the social support that they obtained was measured using the Social Support Questionnaire; and their coping styles were assessed using the Coping Styles Questionnaire. RESULTS: Immediately after the earthquake, the incidence rate of depression in pregnant women was 35.2%, higher than that of the general pregnant population (7%-14%). The EPDS scores were significantly correlated with gestation age at the time of the earthquake, objective support, subjective support, use of support, negative coping style, and positive coping style. The regression analysis indicated that risk factors of prenatal depression include the number of children, relatives wounded, subjective support, and coping styles. A further analysis of the interaction between social support and two types of coping styles with depression showed that there was interaction effect between subjective social support and positive coping styles in relation to EPDS scores. There was an inverse relationship between low EPDS scores and positive coping styles and high social support, and vice versa. CONCLUSION: The timing of the occurrence of the earthquake may not necessarily affect the progress of the illness and recovery from depression, and psychological intervention could be conducted in the immediate aftermath after the earthquake. The impact of coping styles on prenatal depression appeared to be linked with social support. Helping pregnant women to adopt positive coping styles with good social support after a recent major earthquake, which is a stressor, may reduce their chances of developing prenatal depression. PMID- 26270038 TI - Correction: Rule-Based Design of Plant Expression Vectors Using GenoCAD. PMID- 26270037 TI - Non-Invasive Measurement of Skin Microvascular Response during Pharmacological and Physiological Provocations. AB - INTRODUCTION: Microvascular changes in the skin due to pharmacological and physiological provocations can be used as a marker for vascular function. While laser Doppler flowmetry (LDF) has been used extensively for measurement of skin microvascular responses, Laser Speckle Contrast Imaging (LSCI) and Tissue Viability Imaging (TiVi) are novel imaging techniques. TiVi measures red blood cell concentration, while LDF and LSCI measure perfusion. Therefore, the aim of this study was to compare responses to provocations in the skin using these different techniques. METHOD: Changes in skin microcirculation were measured in healthy subjects during (1) iontophoresis of sodium nitroprusside (SNP) and noradrenaline (NA), (2) local heating and (3) post-occlusive reactive hyperemia (PORH) using LDF, LSCI and TiVi. RESULTS: Iontophoresis of SNP increased perfusion (LSCI: baseline 40.9+/-6.2 PU; 10-min 100+/-25 PU; p<0.001) and RBC concentration (TiVi: baseline 119+/-18; 10-min 150+/-41 AU; p = 0.011). No change in perfusion (LSCI) was observed after iontophoresis of NA (baseline 38.0+/-4.4 PU; 10-min 38.9+/-5.0 PU; p = 0.64), while RBC concentration decreased (TiVi: baseline 59.6+/-11.8 AU; 10-min 54.4+/-13.3 AU; p = 0.021). Local heating increased perfusion (LDF: baseline 8.8+/-3.6 PU; max 112+/-55 PU; p<0.001, LSCI: baseline 50.8+/-8.0 PU; max 151+/-22 PU; p<0.001) and RBC concentration (TiVi: baseline 49.2+/-32.9 AU; max 99.3+/-28.3 AU; p<0.001). After 5 minutes of forearm occlusion with prior exsanguination, a decrease was seen in perfusion (LDF: p = 0.027; LSCI: p<0.001) and in RBC concentration (p = 0.045). Only LSCI showed a significant decrease in perfusion after 5 minutes of occlusion without prior exsanguination (p<0.001). Coefficients of variation were lower for LSCI and TiVi compared to LDF for most responses. CONCLUSION: LSCI is more sensitive than TiVi for measuring microvascular changes during SNP-induced vasodilatation and forearm occlusion. TiVi is more sensitive to noradrenaline-induced vasoconstriction. LSCI and TiVi show lower inter-subject variability than LDF. These findings are important to consider when choosing measurement techniques for studying skin microvascular responses. PMID- 26270036 TI - Identification of MiR-205 As a MicroRNA That Is Highly Expressed in Medullary Thymic Epithelial Cells. AB - Thymic epithelial cells (TECs) support T cell development in the thymus. Cortical thymic epithelial cells (cTECs) facilitate positive selection of developing thymocytes whereas medullary thymic epithelial cells (mTECs) facilitate the deletion of self-reactive thymocytes in order to prevent autoimmunity. The mTEC compartment is highly dynamic with continuous maturation and turnover, but the genetic regulation of these processes remains poorly understood. MicroRNAs (miRNAs) are important regulators of TEC genetic programs since miRNA-deficient TECs are severely defective. However, the individual miRNAs important for TEC maintenance and function and their mechanisms of action remain unknown. Here, we demonstrate that miR-205 is highly and preferentially expressed in mTECs during both thymic ontogeny and in the postnatal thymus. This distinct expression is suggestive of functional importance for TEC biology. Genetic ablation of miR-205 in TECs, however, neither revealed a role for miR-205 in TEC function during homeostatic conditions nor during recovery from thymic stress conditions. Thus, despite its distinct expression, miR-205 on its own is largely dispensable for mTEC biology. PMID- 26270039 TI - [Development and Periodicity of Human Exposures in Suicidal Intention Reported to the Centre Erfurt from 2004-2013]. AB - Aim of the Study: Exposures in suicide attempts are demanding for hospitals and poisons information centres (PICs). Therefore, the time characteristics of their frequency were studied. Methods: A retrospective analysis was undertaken of all human exposures reported to Centre Erfurt from the beginning of 2004 to the end of 2013 according to their frequency in the respective year, season, month, weekday, time of the weekday, circumstances of exposure, age and gender. Results: 59.7% of all exposures (n=137 104) were accidental, 23.4% occurred in suicide attempts and 3.3% in substance abuse. 0.3% of the suicide attempts resulted in death. Their number continuously increased from n=2 422 in 2004 to n=3 458 in 2013, but their relative frequency remained almost constant at 23.4%. Their highest numbers were reached in the spring and summer with maxima in July and August and minima in February and September. During the week, the most suicide attempts were observed between Sunday and Tuesday and the least on Friday. Highest rate of suicide attempts was seen at 10 pm and lowest at 6 am. The median of age was 39 years (first quartile 24 years, third quartile 50 years). The female proportion was almost twice as high as the male. Conclusions: Hospitals the Centre Erfurt is serving should be particularly prepared for exposures in suicide attempts in the spring and summer (especially in July and August), at the beginning of the week and shortly before midnight. PMID- 26270040 TI - [Conception and Measurement of Health-related Transition Competence for Adolescents with Chronic Conditions - Development and Testing of a Self-Report Instrument]. AB - Background: The importance of health-related care and self-management responsibilities has been shown in recent research. The aim of this work is the development and psychometric testing of an instrument to assess health-related transition competence. Methods: The instrument was developed with psychometric and conceptual methods in several steps. Based on focus group and expert interviews, an item pool to assess health-related transition competence was developed. The instrument was tested and finalised in a pilot study with adolescents with chronic conditions (N=323). Results: Three subscales "work related preparedness" (3 items), "condition-related knowledge" (3 items) and "health-care competence" (4 items) with proper psychometric properties were identified. The subscales can be combined to a global score. Conclusions: The scales feature good psychometrics. They efficiently facilitate the standardised assessment of health-related transition competence in preparation and progress of the transition. This also enables for outcome assessment of health-care services related to transition competence (e. g., workshops). PMID- 26270041 TI - [Networking, Coordination and Responsibilities based on Health Regionsplus: New Health Political Approaches and Developments in Bavaria]. AB - For many health and health-care problems in the population, there is a need for professional management and coordination instruments as well as a competent local network. The new "Health Regionsplus" in Bavaria offer such a structure. This new concept is presented in the following article. The "Health Regionsplus" aim to improve the population's health, the health-related quality of life, equity in health, as well as to further develop the local health care. The Bavarian State Ministry of Health and Care will support up to 24 regions with a funding of up to 50 000 Euro yearly per "Health Regionplus" until the end of 2019. The structure of "Health Regionsplus" implies the establishment of a coordinating agency that works as a "motor", a health forum on the strategic level and relevant working groups. "Health Regionsplus" involve all relevant stakeholders of the regional health system and are chaired by the district administrator or mayor. They work primarily in the fields of health care and prevention/health promotion but can also pursue other region-specific fields. The Bavarian Health and Food Safety Authority supports and evaluates the "Health Regionsplus". There is also a coordinating office which organises the exchange of information and experience among the "Health Regionsplus". Although such a comprehensive regional approach does not change the statutory decision-making structures and responsibilities it does offer the communities an instrument to involve local needs in their decision making processes. PMID- 26270042 TI - [Problems with Using Hospital Quality Reports as a Secondary Data Source for Health Services Research in Germany]. AB - Background Since 2005, German hospitals are required by law to publish structured quality reports (QRs). Because of the detailed data basis, the QRs are being increasingly used for secondary data analyses in health services research. Up until now, methodological difficulties that can cause distorted results of the analyses have essentially been overlooked. The aim of this study is to systematically list the methodological problems associated with using QR and to suggest solution strategies. Methods The QRs from 2006-2012 form the basis of the analyses and were aggregated in a database using an individualized data linkage procedure. Thereafter, a correlation analysis between a quality indicator and the staffing of hospitals was conducted, serving as an example for both cross sectional as well as longitudinal studies. The resulting methodological problems are described qualitatively and quantitatively, and potential solutions are derived from the statistical literature. Results In each reporting year, 2-15% of the hospitals delivered no QR. In 2-16% of the QRs, it is not recognizable whether a report belongs to a hospital network or a single location. In addition, 6-66% of the location reports falsely contain data from the hospital network. 10% of the hospitals changed their institution code (IC), in 5% of the cases, the same "IC-location-number-combination" was used for different hospitals over the years. Therefore, 10-20% of the QRs cannot be linked with the IC as key variable. As a remedy for the linking of QR, the combination of the IC, the address and the number of beds represents a suitable solution. Using this solution, hospital network reports, location reports and missing reports can be identified and considered in an analysis. Conclusions Secondary data analyses with quality reports provide a high potential for error due to the inconsistent data base and the problems of the data linkage procedure. These can distort calculated parameters and limit the validity of results. Only the unequivocal identification of the reporting hospitals guarantees meaningful results. PMID- 26270043 TI - [Prioritization and Consentation of Criteria for the Appraisal, Funding and Evaluation of Projects from the German Innovationsfonds: A multi-perspective Delphi study]. AB - BACKGROUND: The German Innovationsfonds provides the chance for evidence-based developments of the German healthcare system. OBJECTIVE: Prioritization of recommendations for an effective, efficient, fair, transparent, and sustainable granting of funds through a transparent, evidence-driven consensus-process involving all relevant stakeholder groups. METHODS: Representatives from health and research policy, payers, patient representatives, healthcare providers, and scientists were invited to nominate participants for an electronic 3 round iterative Delphi-study to prioritize the thematic focus, requirements concerning study methods, the team of applicants, evaluation, utilization of study results, and for the selection of reviewers. Criteria considered as relevant by at least 60% of the panel (consensus definition) in the first 2 Delphi rounds were rated as facultative, preferable, or obligatory criteria for project funding. Data were analyzed descriptively. ( REGISTRATION: Datenbank Versorgungsforschung Deutschland VfD_15_003561). RESULTS: All invited stakeholder groups except payers participated. 34 (85%) of 40 nominated representatives participated in the Delphi study. A total of 64 criteria were consented as relevant for project review and funding concerning the thematic focus (n=28), methodological requirements (n=13), requirements for applicants (n=4), for the evaluation (n=4), utilization (n=6), and selection of peer reviewers (n=9). DISCUSSION: It is the collective responsibility of all stakeholders to spend the designated funds as efficient and sustainable as possible. The consented recommendations shall serve decision makers as a resource for the granting of funds and the evaluation of the Innovationsfonds. PMID- 26270044 TI - ["A Little Bit of Switzerland, a Little Bit of Kosovo". Swiss Immigrants from Former Yugoslavia with Type 2 Diabetes. A Qualitative Study' in Analogy to Grounded Theory]. AB - Type 2 diabetes is on the increase among the Swiss immigrants. The cultural background of patients presents new linguistic and sociocultural barriers and gains in importance for health care. In order to develop patient-centred care, it is necessary to focus on different sociocultural aspects in everyday life and experiences of immigrants from the former republics of Yugoslavia with diabetes who have rarely been studied in Switzerland. Based on these insights the needs for counselling can be identified and nursing interventions can be designed accordingly. Using the Grounded Theory approach, 5 interviews were analysed according to the Corbin and Strauss coding paradigm. The central phenomenon found is the experience to live in 2 different cultures. The complexity arises from the tension living in 2 cultural backgrounds at the same time. It turns out that in the country of origin the immigrants adjust their disease management. The changing daily rhythm and the more traditional role model affect aspects of their disease management such as diet and/or drug therapy. The different strategies impact the person's roles, emotions, their everyday lives and their families. It provides an insight into the perspective of Swiss immigrants from the former republics of Yugoslavia suffering from diabetes. Many questions are still unanswered and further research will be required. PMID- 26270045 TI - Overexpression of MMP Family Members Functions as Prognostic Biomarker for Breast Cancer Patients: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Matrix metalloproteinases (MMPs) are regarded to be relevant to the prognosis of breast cancer. Numerous studies have confirmed the association between MMPs and tumor growth, invasion and metastasis in breast cancer. However, their prognostic values for survival in patients with breast cancer remain controversial. Hence, a meta-analysis was performed to clarify a more accurate estimation of the role of MMPs on prognosis of breast cancer patients. METHOD: A systemic electronic search was conducted in PubMed, Embase and Web of science databases to identify eligible studies, which were associated with the relationship between MMPs and prognosis of breast cancer. The correlation in random-effect model was evaluated by using the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: A total of 28 studies covering 4944 patients were included for meta-analysis. A summary hazard ratio (HR) of all studies was calculated, as well as the sub-group HRs. The combined HRs calculated by either univariate or multivariate analysis both suggested that overexpression of MMPs had an unfavorable impact on overall survival (OS) (HR = 1.694, 95%CI: 1.347 2.129, P < 0.001; HR = 1.611, 95%CI: 1.419-1.830, P < 0.001, respectively). And the univariate analysis showed that patients with overexpression of MMPs had worse relapse-free survival (RFS) (HR = 1.969, 95%CI: 1.460-2.655, P < 0.001) in all eligible studies. In the sub-group analyses, HRs of MMP-9 positivity with poor OS were 1.794 (95%CI: 1.330-2.420, P < 0.001) and 1.709 (95%CI: 1.157-2.526, P = 0.007) which were separately evaluated by univariate and multivariate analysis. A small number of articles demonstrated that MMP-2 overexpression was not related with shorter OS (HR = 1.400, 95%CI: 0.610-3.029, P = 0.427). Four studies included in the OS analysis of MMPs expression in serum suggested that positive expression of serum MMPs may be an unfavorable factor (HR = 1.630, 95%CI: 1.065-2.494) for breast cancer patients. No publication bias was observed in the current meta-analysis. CONCLUSIONS: Our findings suggested that MMPs overexpression (especially MMP-9, MMP-2, MMPs overexpression in serum) might indicate a higher risk of poor prognosis in breast cancer. Larger prospective studies are further needed to estimate the prognostic values of MMPs overexpression. PMID- 26270046 TI - Aphid Parasitoid Mothers Don't Always Know Best through the Whole Host Selection Process. AB - Parasitoid host selection behaviour has been extensively studied in experimentally simplified tritrophic systems formed by one single food chain (one plant, one herbivore and one parasitoid species). The "Mother knows best" hypothesis predicts that the preference for a plant-host complex should be positively correlated with plant quality for offspring performance. We studied the host selection behaviour of the generalist endoparasitoid Aphidius matricariae towards the black bean aphid Aphis fabae in the intercrop system including Vicia faba as a focal plant and its companion plant Camelina sativa. Dual-choice laboratory bioassays revealed that parasitoid females preferred to orientate towards (1) the plant-aphid complex over the non-infested plant whatever the complex (2) the C. sativa-A. fabae complex over the V. faba-A. fabae complex. In dual choice attack rate bioassays, parasitoid females showed more interest towards the aphids on C. sativa but paradoxically chose to oviposit more in aphids on V. faba. Ultimately, parasitoids that had developed on the V. faba A. fabae complex exhibited better fitness parameters. By demonstrating that parasitoid females were able to discriminate the aphid host that offered the highest fitness to their offspring but selected beforehand the least suitable plant-aphid complex, we provide key insight into the disruption in their host selection behaviour potentially triggered by diverse habitats. This suggests that the "Mother knows best" hypothesis could be thwarted by increasing the complexity of the studied systems. PMID- 26270047 TI - A Dissolved Oxygen Threshold for Shifts in Bacterial Community Structure in a Seasonally Hypoxic Estuary. AB - Pelagic ecosystems can become depleted of dissolved oxygen as a result of both natural processes and anthropogenic effects. As dissolved oxygen concentration decreases, energy shifts from macrofauna to microorganisms, which persist in these hypoxic zones. Oxygen-limited regions are rapidly expanding globally; however, patterns of microbial communities associated with dissolved oxygen gradients are not yet well understood. To assess the effects of decreasing dissolved oxygen on bacteria, we examined shifts in bacterial community structure over space and time in Hood Canal, Washington, USA-a glacial fjord-like water body that experiences seasonal low dissolved oxygen levels known to be detrimental to fish and other marine organisms. We found a strong negative association between bacterial richness and dissolved oxygen. Bacterial community composition across all samples was also strongly associated with the dissolved oxygen gradient, and significant changes in bacterial community composition occurred at a dissolved oxygen concentration between 5.18 and 7.12 mg O2 L(-1). This threshold value of dissolved oxygen is higher than classic definitions of hypoxia (<2.0 mg O2 L(-1)), suggesting that changes in bacterial communities may precede the detrimental effects on ecologically and economically important macrofauna. Furthermore, bacterial taxa responsible for driving whole community changes across the oxygen gradient are commonly detected in other oxygen-stressed ecosystems, suggesting that the patterns we uncovered in Hood Canal may be relevant in other low oxygen ecosystems. PMID- 26270048 TI - Nodding Syndrome May Be Only the Ears of the Hippo. PMID- 26270049 TI - Socio-Economic Differentials in Impoverishment Effects of Out-of-Pocket Health Expenditure in China and India: Evidence from WHO SAGE. AB - BACKGROUND AND OBJECTIVES: The provision of affordable health care is generally considered a fundamental goal of a welfare state. In addition to its role in maintaining and improving the health status of individuals and households, it impacts the economic prosperity of a society through its positive effects on labor productivity. Given this context, this paper assesses socioeconomic differentials in the impact of out-of-pocket-health-expenditure (OOPHE) on impoverishment in China and India, two of the fastest growing economies of the world. DATA AND METHODS: The paper uses data from the World Health Organisation's Study on Global Ageing and Adult Health (WHO SAGE), and Bivariate as well as Multivariate analyses for investigating the socioeconomic-differentials in the impact of out-of-pocket-health-expenditure (OOPHE) on impoverishment in China and India. RESULTS AND CONCLUSIONS: Annually, about 7% and 8% of the population in China and India, respectively, fall in poverty due to OOPHE. Also, the percentage shortfall in income for the population from poverty line due to OOPHE is 2% in China and 1.3% in India. Further, findings from the multivariate analysis indicate that lower wealth status and inpatient as well as outpatient care increase the odds of falling below poverty line significantly (with the extent much higher in the case of in-patient care) due to OOPHE in both China and India. In addition, having at least an under-5 child in the household, living in rural areas and having a household head with no formal education increases the odds of falling below poverty line significantly (compared to a head with college level education) due to OOPHE in China; whereas having at least an under-5 child, not having health insurance and residing in rural areas increases the odds of becoming poor significantly due to OOPHE in India. PMID- 26270050 TI - Implications of Pericardial, Visceral and Subcutaneous Adipose Tissue on Vascular Inflammation Measured Using 18FDG-PET/CT. AB - OBJECTIVE: Pericardial adipose tissue (PAT) is associated with adverse cardiometabolic risk factors and cardiovascular disease (CVD). However, the relative implications of PAT, abdominal visceral and subcutaneous adipose tissue on vascular inflammation have not been explored. METHOD AND RESULTS: We compared the association of PAT, abdominal visceral fat area (VFA), and subcutaneous fat area (SFA) with vascular inflammation, represented as the target-to-background ratio (TBR), the blood-normalized standardized uptake value measured using 18F Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET) in 93 men and women without diabetes or CVD. Age- and sex-adjusted correlation analysis showed that PAT, VFA, and SFA were positively associated with most cardiometabolic risk factors, including systolic blood pressure, LDL-cholesterol, triglycerides, glucose, insulin resistance and high sensitive C-reactive proteins (hsCRP), whereas they were negatively associated with HDL-cholesterol. In particular, the maximum TBR (maxTBR) values were positively correlated with PAT and VFA (r = 0.48 and r = 0.45, respectively; both P <0.001), whereas SFA showed a relatively weak positive relationship with maxTBR level (r = 0.31, P = 0.003). CONCLUSION: This study demonstrated that both PAT and VFA are significantly and similarly associated with vascular inflammation and various cardiometabolic risk profiles. PMID- 26270052 TI - The Ebola Virus: From Basic Research to a Global Health Crisis. PMID- 26270053 TI - Development and Evaluation of a Rapid Antigen Detection and Serotyping Lateral Flow Antigen Detection System for Foot-and-Mouth Disease Virus. AB - We developed a lateral flow strip using monoclonal antibodies (MAbs) which allows for rapid antigen detection and serotyping of foot-and-mouth disease virus (FMDV). This FMDV serotyping strip was able to detect all 7 serotypes and distinguish serotypes O, A, C and Asia1. Its sensitivities ranged from 10(3) to 10(4) of a 50% tissue culture infectious dose of each FMDV stain; this is equal to those of the commercial product Svanodip (Boehringer Ingelheim Svanova, Uppsala, Sweden), which can detect all seven serotypes of FMDV, but does not distinguish them. Our evaluation of the FMDV serotyping strip using a total of 118 clinical samples (vesicular fluids, vesicular epithelial emulsions and oral and/or nasal swabs) showed highly sensitive antigen detection and accuracy in serotyping in accordance with ELISA or RT-PCR. To the best of our knowledge, this is the first report on any FMDV serotyping strip that provides both rapid antigen detection and serotyping of FMDV at the same time on one strip without extra devices. This method will be useful in both FMD-free countries and FMD-infected countries, especially where laboratory diagnosis cannot be carried out. PMID- 26270051 TI - In-Vivo Gene Signatures of Mycobacterium tuberculosis in C3HeB/FeJ Mice. AB - Despite considerable progress in understanding the pathogenesis of Mycobacterium tuberculosis (Mtb), development of new therapeutics and vaccines against it has proven difficult. This is at least in part due to the use of less than optimal models of in-vivo Mtb infection, which has precluded a study of the physiology of the pathogen in niches where it actually persists. C3HeB/FeJ (Kramnik) mice develop human-like lesions when experimentally infected with Mtb and thus make available, a faithful and highly tractable system to study the physiology of the pathogen in-vivo. We compared the transcriptomics of Mtb and various mutants in the DosR (DevR) regulon derived from Kramnik mouse granulomas to those cultured in-vitro. We recently showed that mutant DeltadosS is attenuated in C3HeB/FeJ mice. Aerosol exposure of mice with the mutant mycobacteria resulted in a substantially different and a relatively weaker transcriptional response (< = 20 genes were induced) for the functional category 'Information Pathways' in Mtb:DeltadosR; 'Lipid Metabolism' in Mtb:DeltadosT; 'Virulence, Detoxification, Adaptation' in both Mtb:DeltadosR and Mtb:DeltadosT; and 'PE/PPE' family in all mutant strains compare to wild-type Mtb H37Rv, suggesting that the inability to induce DosR functions to different levels can modulate the interaction of the pathogen with the host. The Mtb genes expressed during growth in C3HeB/FeJ mice appear to reflect adaptation to differential nutrient utilization for survival in mouse lungs. The genes such as glnB, Rv0744c, Rv3281, sdhD/B, mce4A, dctA etc. downregulated in mutant DeltadosS indicate their requirement for bacterial growth and flow of carbon/energy source from host cells. We conclude that genes expressed in Mtb during in-vivo chronic phase of infection in Kramnik mice mainly contribute to growth, cell wall processes, lipid metabolism, and virulence. PMID- 26270054 TI - In Vivo Correlation of Glucose Metabolism, Cell Density and Microcirculatory Parameters in Patients with Head and Neck Cancer: Initial Results Using Simultaneous PET/MRI. AB - OBJECTIVE: To demonstrate the feasibility of simultaneous acquisition of 18F-FDG PET, diffusion-weighted imaging (DWI) and T1-weighted dynamic contrast-enhanced MRI (T1w-DCE) in an integrated simultaneous PET/MRI in patients with head and neck squamous cell cancer (HNSCC) and to investigate possible correlations between these parameters. METHODS: 17 patients that had given informed consent (15 male, 2 female) with biopsy-proven HNSCC underwent simultaneous 18F-FDG PET/MRI including DWI and T1w-DCE. SUVmax, SUVmean, ADCmean, ADCmin and Ktrans, kep and ve were measured for each tumour and correlated using Spearman's rho. RESULTS: Significant correlations were observed between SUVmean and Ktrans (rho = 0.43; p <= 0.05); SUVmean and kep (rho = 0.44; p <= 0.05); Ktrans and kep (rho = 0.53; p <= 0.05); and between kep and ve (rho = -0.74; p <= 0.01). There was a trend towards statistical significance when correlating SUVmax and ADCmin (rho = 0.35; p = 0.08); SUVmax and Ktrans (rho = 0.37; p = 0.07); SUVmax and kep (rho = 0.39; p = 0.06); and ADCmean and ve (rho = 0.4; p = 0.06). CONCLUSION: Simultaneous 18F-FDG-PET/MRI including DWI and T1w-DCE in patients with HNSCC is feasible and allows depiction of complex interactions between glucose metabolism, microcirculatory parameters and cellular density. PMID- 26270055 TI - Listening to music helps reduce pain and anxiety after surgery, review shows. PMID- 26270056 TI - Cerebral Inefficient Activation in Schizophrenia Patients and Their Unaffected Parents during the N-Back Working Memory Task: A Family fMRI Study. AB - BACKGROUND: It has been suggested that working memory deficits is a core feature of symptomatology of schizophrenia, which can be detected in patients and their unaffected relatives. The impairment of working memory has been found related to the abnormal activity of human brain regions in many functional magnetic resonance imaging (fMRI) studies. This study investigated how brain region activation was altered in schizophrenia and how it was inherited independently from performance deficits. METHOD: The authors used fMRI method during N-back task to assess working memory related cortical activation in four groups (N = 20 in each group, matching task performance, age, gender and education): schizophrenic patients, their unaffected biological parents, young healthy controls for the patients and older healthy controls for their parents. RESULTS: Compared to healthy controls, patients showed an exaggerated response in the right dorsolateral prefrontal cortex (brodmann area [BA] 46) and bilateral ventrolateral prefrontal cortex, and had reduced activation in bilateral dorsolateral prefrontal cortex (BA 9). In the conjunction analysis, the effect of genetic risk (parents versus older control) shared significantly overlapped activation with effect of disease (patients versus young control) in the right middle frontal gyrus (BA 46) and left inferior parietal gyrus (BA 40). CONCLUSIONS: Physiological inefficiency of dorsal prefrontal cortex and compensation involvement of ventral prefrontal cortex in working memory function may one physiological characteristics of schizophrenia. And relatively inefficient activation in dorsolateral prefrontal cortex probably can be a promising intermediate phenotype for schizophrenia. PMID- 26270057 TI - Influence of Soil Properties on Soldierless Termite Distribution. AB - In tropical rainforests, termites constitute an important part of the soil fauna biomass, and as for other soil arthropods, variations in soil composition create opportunities for niche partitioning. The aim of this study was twofold: first, we tested whether soil-feeding termite species differ in the foraging substrate; second, we investigated whether soil-feeding termites select their foraging sites to enhance nutrients intake. To do so, we collected termites and analysed the composition and structure of their feeding substrates. Although Anoplotermes group members are all considered soil-feeders, our results show that some species specifically feed on abandoned termite nests and very rotten wood, and that this substrate selection is correlated with previous stable isotope analyses, suggesting that one component of niche differentiation among species is substrate selection. Our results show that the composition and structure of bare soils on which different termite species foraged do not differ, suggesting that there is no species specialization for a particular type of bare soil. Finally, the bare soil on which termites forage does not differ from random soil samples. Overall, our results suggest that few species of the Anoplotermes-group are specialized toward substrates rich in organic matter, but that the vast majority forage on soil independently of its structural and chemical composition, being ecologically equivalent for this factor. PMID- 26270058 TI - Bicyclist Deaths Associated with Motor Vehicle Traffic - United States, 1975 2012. AB - Physical activity, including bicycling, is linked with multiple health benefits. However, although bicycles account for only about 1% of trips across all modes of transportation, on a per trip basis, bicyclists die on U.S. roads at a rate double that of vehicle occupants. In 2009, an estimated 392 billion trips (across all modes) were taken in the United States, including 4.1 billion bicycle trips, and 33,808 deaths occurred on U.S roadways (across all modes), including 630 bicyclist deaths. This report examines mortality trends among cyclists using national collision data from the Fatality Analysis Reporting System (FARS) for the period 1975-2012. Annual rates for cyclist mortality decreased 44%, from 0.41 to 0.23 deaths per 100,000 during this period, with the steepest decline among children aged <15 years. In recent years, reductions in cyclist deaths have slowed. However, age-specific cyclist mortality rates for adults aged 35-74 years have increased since 1975. Multifaceted approaches to bicyclist safety have been shown to be effective in increasing bicycling while decreasing traffic injuries and fatalities. With U.S. adults choosing to walk and cycle more, implementation of these approaches might help counter recent increases in adult cyclist deaths. PMID- 26270059 TI - Surveillance for Waterborne Disease Outbreaks Associated with Drinking Water - United States, 2011-2012. AB - Advances in water management and sanitation have substantially reduced waterborne disease in the United States, although outbreaks continue to occur. Public health agencies in the U.S. states and territories* report information on waterborne disease outbreaks to the CDC Waterborne Disease and Outbreak Surveillance System (http://www.cdc.gov/healthywater/surveillance/index.html). For 2011-2012, 32 drinking water-associated outbreaks were reported, accounting for at least 431 cases of illness, 102 hospitalizations, and 14 deaths. Legionella was responsible for 66% of outbreaks and 26% of illnesses, and viruses and non-Legionella bacteria together accounted for 16% of outbreaks and 53% of illnesses. The two most commonly identified deficiencies? leading to drinking water-associated outbreaks were Legionella in building plumbingS systems (66%) and untreated groundwater (13%). Continued vigilance by public health, regulatory, and industry professionals to identify and correct deficiencies associated with building plumbing systems and groundwater systems could prevent most reported outbreaks and illnesses associated with drinking water systems. PMID- 26270060 TI - Outbreaks Associated With Environmental and Undetermined Water Exposures - United States, 2011-2012. AB - Exposures to contaminated water can lead to waterborne disease outbreaks associated with various sources, including many that are classified and reported separately as drinking water or recreational water. Waterborne disease outbreaks can also involve a variety of other exposures (e.g., consuming water directly from backcountry or wilderness streams, or inhaling aerosols from cooling towers and ornamental fountains). Additionally, outbreaks might be epidemiologically linked to multiple water sources or may not have a specific water source implicated. PMID- 26270061 TI - Suspected Palytoxin Inhalation Exposures Associated with Zoanthid Corals in Aquarium Shops and Homes - Alaska, 2012-2014. AB - On August 12, 2014, an Anchorage hospital notified the Alaska Section of Epidemiology (SOE) that a middle-aged male resident of Anchorage (patient A) had arrived in the emergency department with possible palytoxin exposure. Patient A complained of a bitter metallic taste, fever, weakness, cough, and muscle pain 7 8 hours after introduction of live zoanthid coral into his home aquarium. Palytoxin, a potent toxin known to produce the reported effects, is contained in zoanthid marine corals. PMID- 26270062 TI - Investigation of Tuberculosis in a High School - San Antonio, Texas, 2012. AB - On February 21, 2012, the San Antonio Metropolitan Health District (SAMHD) Tuberculosis Clinic was notified that two students at Madison High School had laboratory-confirmed pulmonary tuberculosis (TB). During March-September 2012, public health officials from SAMHD collaborated with the school district to conduct an outbreak investigation that included performing tuberculin skin tests (TSTs) on high-risk contacts of active TB patients. To ensure compliance, all TSTs were performed at the school. Initial screening was conducted as soon as a contact was identified and was followed by a second TST >=8 weeks after the patients with active TB were removed from the school. All positive TSTs were confirmed with an interferon gamma release assay (IGRA) (T-Spot.TB, Oxford Immunotec, Inc.) performed by SAMHD laboratory services. IGRA tests can provide additional evidence of infection to encourage acceptance and adherence of foreign born patients who believe their positive TST is attributable to Bacille Calmette Guerin vaccination and might also prompt greater acceptance of treatment for latent TB infection compared with a positive TST alone. PMID- 26270063 TI - Use and Interpretation of a Rapid Respiratory Syncytial Virus Antigen Detection Test Among Infants Hospitalized in a Neonatal Intensive Care Unit - Wisconsin, March 2015. AB - On March 25, 2015, the Wisconsin Division of Public Health was notified of a possible respiratory syncytial virus (RSV) infection outbreak among infants hospitalized in a neonatal intensive care unit (NICU). On March 23, the index patient (neonate A), aged 3 days, had feeding intolerance and apnea. A nasopharyngeal swab specimen collected from neonate A was tested using a single manufacturer rapid RSV antigen detection test (RRADT) at the hospital laboratory; the result was positive. The following day, because of concern about the possibility of more widespread RSV infection, RRADT was used to test nasopharyngeal swab specimens from neonate B, aged 1 month, who had resided in a different hospital room in the NICU and had developed an increased oxygen requirement, apnea, and poor feeding that day, as well as from two asymptomatic neonates who were hospitalized in the same room with neonate A; all three were positive. Later that day, nasopharyngeal swab specimens from the remaining 16 asymptomatic NICU patients were tested using the same RRADT; seven tests were positive, making a total of 11 positives. All 20 RRADTs were performed at the hospital laboratory. PMID- 26270064 TI - Development of a Novel Process Integrating the Treatment of Sludge Reject Water and the Production of Polyhydroxyalkanoates (PHAs). AB - Polyhydroxyalkanoates (PHAs) from activated sludge and renewable organic material can become an alternative product to traditional plastics since they are biodegradable and are produced from renewable sources. In this work, the selection of PHA storing bacteria was integrated with the side stream treatment of nitrogen removal via nitrite from sewage sludge reject water. A novel process was developed and applied where the alternation of aerobic-feast and anoxic famine conditions accomplished the selection of PHA storing biomass and nitrogen removal via nitrite. Two configurations were examined: in configuration 1 the ammonium conversion to nitrite occurred in the same reactor in which the PHA selection process occurred, while in configuration 2 two separate reactors were used. The results showed that the selection of PHA storing biomass was successful in both configurations, while the nitrogen removal efficiency was much higher (almost 90%) in configuration 2. The PHA selection degree was evaluated by the volatile fatty acid (VFA) uptake rate (-qVFAs) and the PHA production rate (qPHA), which were 239 +/- 74 and 89 +/- 7 mg of COD per gram of active biomass (Xa) per hour, respectively. The characterization of the biopolymer recovered after the accumulation step, showed that it was composed of 3-hydroxybutyrate (3HB) (60%) and 3-hydroxyvalerate (3HV) (40%). The properties associated with the produced PHA suggest that they are suitable for thermoplastic processing. PMID- 26270065 TI - CARES((r)) Dementia Care for FamiliesTM: Effects of Online, Psychoeducational Training on Knowledge of Person-Centered Care and Satisfaction. AB - Challenges to intervention use among family caregivers of individuals with dementia include availability and timing of delivery. The current study sought to determine whether an online, psychoeducational intervention for dementia family caregivers, CARES((r)) Dementia Care for FamiliesTM (CARES for Families), improved and enhanced dementia caregivers' knowledge of person-centered care approaches. Forty-one family members completed pre- and posttest surveys that assessed improvement in dementia care knowledge, and multiple close- and open ended items examined how the CARES for Families online modules benefited users at posttest. A paired t test demonstrated a significant and considerable increase in dementia care knowledge among family caregivers (p < 0.001); caregivers also indicated that CARES for Families' content, flexibility, and use of actual family caregivers and individuals with dementia in video care vignettes were strengths. The findings suggest that CARES for Families can offer an efficient supplement to holistic dementia care that gerontological nurses provide. PMID- 26270066 TI - Is there any Influence of Journal Impact Factor on the Citation Index of Articles Published in Brazilian Journals with International Scope? PMID- 26270067 TI - Low-Flow Aortic Stenosis and Reduced Ejection Fraction: New Insights. PMID- 26270068 TI - Case 02/2015 - A 67 Year-Old Woman with Sudden Cardiogenic Shock in the 7th Day after Acute Myocardial Infarction. PMID- 26270069 TI - ST Elevation Myocardial Infarction Early After Heart Transplantation. PMID- 26270070 TI - Multidetector Computed Tomographic Characterization of a Left Atrial Myxoma. PMID- 26270071 TI - Association between Aortic Valve Sclerosis and Adverse Cardiovascular Events. PMID- 26270072 TI - Neurodegeneration and Identity. AB - There is a widespread notion, both within the sciences and among the general public, that mental deterioration can rob individuals of their identity. Yet there have been no systematic investigations of what types of cognitive damage lead people to appear to no longer be themselves. We measured perceived identity change in patients with three kinds of neurodegenerative disease: frontotemporal dementia, Alzheimer's disease, and amyotrophic lateral sclerosis. Structural equation models revealed that injury to the moral faculty plays the primary role in identity discontinuity. Other cognitive deficits, including amnesia, have no measurable impact on identity persistence. Accordingly, frontotemporal dementia has the greatest effect on perceived identity, and amyotrophic lateral sclerosis has the least. We further demonstrated that perceived identity change fully mediates the impact of neurodegenerative disease on relationship deterioration between patient and caregiver. Our results mark a departure from theories that ground personal identity in memory, distinctiveness, dispositional emotion, or global mental function. PMID- 26270073 TI - Crowding in Visual Working Memory Reveals Its Spatial Resolution and the Nature of Its Representations. AB - Spatial resolution fundamentally limits any image representation. Although this limit has been extensively investigated for perceptual representations by assessing how neighboring flankers degrade the perception of a peripheral target with visual crowding, the corresponding limit for representations held in visual working memory (VWM) is unknown. In the present study, we evoked crowding in VWM and directly compared resolution in VWM and perception. Remarkably, the spatial resolution of VWM proved to be no worse than that of perception. However, mixture modeling of errors caused by crowding revealed the qualitatively distinct nature of these representations. Perceptual crowding errors arose from both increased imprecision in target representations and substitution of flankers for targets. By contrast, VWM crowding errors arose exclusively from substitutions, which suggests that VWM transforms analog perceptual representations into discrete items. Thus, although perception and VWM share a common resolution limit, exceeding this limit reveals distinct mechanisms for perceiving images and holding them in mind. PMID- 26270074 TI - Comparative Effects of Ischemic Preconditioning and Iron Chelation in Hepatectomy. AB - PURPOSE/AIM: Major hepatectomies can result in severe ischemia/reperfusion (I/R) injury of the liver. The aim of this survey is to comparatively evaluate the effects of a surgical and a pharmacological hepatoprotective modality on the liver remnant in a porcine model of hepatectomy. MATERIAL AND METHODS: Twenty-one Landrace pigs were randomly divided into three groups: a control group (CON) (n = 7), an Ischemic Preconditioning (PRE) group (n = 7) and a Desferoxamine (DFX) treated one (n = 7). Animals were subjected to 120 min of liver ischemia with subsequent 75% hepatectomy followed by 24-hr reperfusion. In all animals, continuous intracranial pressure (ICP) monitoring was employed. Blood samples were collected at t0, t6, t12, and t24 hrs after reperfusion. Liver remnant specimens were excised for histological examination. RESULTS: In the PRE group, ICP was statistically lower at t6 time point compared to CON group and in comparison with t0. In addition, ICP was significantly lower at all-time points after reperfusion in the DFX group. Finally, with regard to DFX and PRE group correlation, ICP was significantly lower at t0, t12, and t24 time points after reperfusion in the DFX group. In the PRE group, NH3 levels were significantly lower at t12 after reperfusion compared to CON and DFX groups. Histological evaluation elucidated significantly less hepatocellular necrosis, apoptosis, and degeneration in the PRE and DFX groups correlated to CON group. CONCLUSIONS: Both hepatoprotective modalities including PRE and DFX administration are associated with lower ICP levels and correlated with attenuated liver remnant injury. PMID- 26270075 TI - Enzymic Digestion of Biological Specimens for Drug Analysis. AB - In the first part of this paper, procedures using beta-glucuronidase for the analysis of drug conjugates in urine are reviewed and compared to the more classical techniques of acid hydrolysis. Morphine-3-beta-D-glucuronide is one of the most commonly encountered drug conjugates that may be either acid hydrolyzed or enzyme hydrolyzed to yield free morphine. Because of its rapidity of method and high yield of drug, acid hydrolysis of morphine glucuronide is still the most popularly employed technique for the release of free morphine. However, enzyme hydrolysis has been shown to enjoy virtually the same rapid hydrolysis and high yield of free drug, and it does not hydrolyze acid-labile drugs that might be present. In the second part of this paper, a discussion of the benefits of enzyme hydrolysis of tissues, hair, etc., for the release of drugs is presented. Such benefits include milder conditions, improved yields of drug, cleaner extracts, and the prevention of emulsions, especially when compared to acid hydrolysis. Several proteolytic enzymes have been employed for tissue digestion, including pepsin, subtilisin Carlsberg, papain, trypsin, neutrase, and others. While no one enzyme system has surfaced as being clearly the most effective in releasing drugs from tissues, several have been found to be quite effective, e.g., the proteolytic enzyme subtilisin Carlsberg. The proteolytic enzyme papain has also been recommended because of its long shelf life, low cost, and excellent recovery of drugs from tissues. PMID- 26270076 TI - Estimation of Postmortem Interval Using Arthropod Development and Successional Patterns. AB - Insects are frequently the first organisms to arrive at a dead body. By their activities they begin a biological clock that will allow for an estimation of the postmortem interval (PMI). In this publication, the two general approaches to estimation of the PMI using entomological data are reviewed: (a) use of individual species developmental patterns; and (b) use of arthropod succession data. Recent advances in studies of the biologies of various Diptera (flies) have allowed for more accurate estimates, as have recent detailed studies of the roles of various arthropods in the decomposition process. Five stages of decomposition (fresh, bloated, decay, post-decay, and skeletal) are suggested as reference points in the decomposition process. These stages are largely artificial, but serve as convenient references in court situations. Factors that may delay invasion of the remains by arthropods or alter developmental patterns, such as wrapping of the body, climate, or presence of drugs and toxins in the remains, are discussed. A general plan of approach to the estimation of PMI using entomological data is presented. PMID- 26270077 TI - Illicit Production of Cocaine. AB - The predominant methods currently used for illicit production of cocaine are described. For illicit natural cocaine (i.e., from coca leaf), this includes production of coca paste from coca leaf via both the solvent and acid extraction techniques, purification of coca paste to cocaine base, and conversion of cocaine base to cocaine hydrochloride. For illicit synthetic cocaine (i.e., synthesized from precursor chemicals), the classic five-step synthetic route used in all clandestine laboratories seized to date is summarized. The origins of the most common alkaloidal impurities and processing/synthetic by-products typically identified in illicit natural, illicit synthetic, and pharmaceutical cocaine are discussed. Forensic differentiation of exhibits arising from the various production methods are addressed both in terms of overall product purity and the presence/absence of these impurities and by-products. PMID- 26270078 TI - Metabolic Precursors to Amphetamine and Methamphetamine. AB - Analysis and interpretation of amphetamine results is a challenging process made difficult by a number of factors. One of the complications comes from determination of the origin of amphetamine or methamphetamine in a sample. Given the relatively rare occasions that either of these two drugs are prescribed, legal prescription of one of these drugs is seldom a reason for positive findings. A number of other precursor compounds are metabolized by the body to amphetamine or methamphetamine, many of which could be used for legitimate reasons. Fourteen different metabolic precursors of amphetamine or methamphetamine are included in this review. They are amphetaminil, benzphetamine, clobenzorex, deprenyl, dimethylamphetamine, ethylamphetamine, famprofazone, fencamine, fenethylline, fenproporex, furfenorex, mefenorex, mesocarb, and prenylamine. Medical use, metabolism, analysis, and interpretation are described to afford sufficient information to evaluate the possible involvement of these drugs in positive amphetamine or methamphetamine results. PMID- 26270079 TI - Structural Characterization of Ginsenosides from Flower Buds of Panax ginseng by RRLC-Q-TOF MS. AB - Ginseng flower bud as a part of Panax ginseng has received much attention as a valuable functional food with medicinal potential. A few studies focused on systematic and comprehensive studies on its major ingredients. This study aims to rapidly characterize ginsenosides in ginseng flower buds and provide scientific basis for developing functional food, exploiting pharmaceutical effects and making full use of ginseng resources. A rapid resolution liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (RRLC-Q-TOF-MS) method was developed for rapid qualitative and quantitative analysis of ginsenosides in ginseng flower buds. The compounds were identified by comparing retention time of the reference standards, accurate mass measurement and the fragment ions obtained from RRLC-Q-TOF-MS/MS analyses. A total of 14 kinds of ginsenosides were identified and 5 kinds of malonyl-ginsenosides were first tentatively identified in ginseng flower buds. Ten kinds of main ginsenosides were quantitatively analyzed. The developed RRLC-Q-TOF-MS method was demonstrated as an effective analytical means for rapid characterization of the ginsenosides in flower buds of P. ginseng. The research result is valuable for quality control, assessment of authenticity and stability evaluation of ginseng flower buds. PMID- 26270080 TI - Modified QuEChERS in combination with dispersive liquid-liquid microextraction based on solidification of the floating organic droplet method for the determination of organophosphorus pesticides in milk samples. AB - In this work, a rapid, environment friendly and sensitive method was established for the extraction and analysis of five organophosphorus pesticides (OPPs) (chlorpyrifos, chlorpyrifos-methyl, isocarbophos, malathion and phorate) in milk samples by means of gas chromatography-flame photometric detection. The pesticides were first extracted with acetonitrile from milk samples by using the modified "quick, easy, cheap, effective, rugged, and safe" (QuEChERS) method. No other clean-up was required after extraction. Then the above-mentioned acetonitrile extract was concentrated by using the dispersive liquid-liquid microextraction combined with solidification of floating organic droplets technique. Several factors that could influence the extraction efficiency, such as type of extraction solvent, disperser solvent, volume of extraction and disperser solvent, salt effect, sample pH, and extraction time, were investigated and optimized. As a result, 15 uL of 1-dodecanol were used as the extractant because of its lower toxicity, 300 uL methanol was chosen as dispersant and the extraction time was set to 1 min. Under the optimized conditions, good linearity was exhibited from 0.01 to 1.0 mg/L with the correlation coefficients higher than 0.9968. The limits of detection of the five OPPs were ranged in 0.1-0.3 MUg/L, and the limits of quantification were at the range of 0.3-1.0 MUg/L. Moreover, the recoveries of the target analytes from milk samples at spiking levels of 0.01, 0.05 and 0.1 mg/L were between 80.5 and 106.5% with the relative standard deviations varied from 3.6 to 6.3%. This method has been successfully applied to detect OPPs in real milk samples. PMID- 26270081 TI - Hollow Fiber Liquid Based Microextraction of Nalidixic Acid in Urine Samples Using Aliquat 336 as a Carrier Combined with High-Performance Liquid Chromatography. AB - A new and simple hollow fiber liquid-phase microextraction was used in conjunction with HPLC for the extraction and quantitative determination of nalidixic acid (NA) in human urine samples. This study considers this technique an alternative to common methods of hollow fiber microextraction based on pH gradient and electromembrane extraction of NA in human urine samples. In this research, the drug was extracted from the source phase (donor phase) into a modified organic phase with Aliquat 336 (hydrophobic ion-pair reagent) as a carrier able to impregnate pores of the hollow fiber. In this study, the effects of several factors were tested on the extraction efficiency of the drug. Under optimum conditions, the linearity of the method was observed over the range 0.05 2.0 ug mL(-1) with a correlation coefficient of r = 0.9983. The results of tests on the method determined a good sensitivity with a limit of detection of 0.008 ug mL(-1). The intra-day relative standard deviation (n = 9) for 0.8 ug mL(-1) was 6.2%, and the inter-day relative standard deviation (n = 5) for 0.8 ug mL(-1) was 5.6%. This new strategy was successfully applied to analyze a real urine sample with satisfactory results. PMID- 26270083 TI - Precise Nanoscale Surface Modification and Coating of Macroscale Objects: Open Environment in Loco Atomic Layer Deposition on an Automobile. AB - The fundamental chemical reaction conditions that define atomic layer deposition (ALD) can be achieved in an open environment on a macroscale surface too large and complex for typical laboratory reactor-based ALD. We describe the concept of in loco ALD using conventional modulated reactant flow through a surface-mounted "ALD delivery head" to form a precise nanoscale Al2O3 film on the window of a parked automobile. Analysis confirms that the processes eliminated ambient water contamination and met other conditions that define ALD growth. Using this tool, we demonstrate open-ambient patterned deposition, metal corrosion protection, and polymer surface modification. PMID- 26270082 TI - Clinical Outcome and Quality of Life After a Multimodal Therapy Approach to Ear Keloids. AB - IMPORTANCE: Keloids are fibroproliferative scars that can cause a huge psychological burden and severe problems for patients, such as depression. Many treatment options exist; however, recurrence rates, especially with monotherapy, remain high. OBJECTIVE: To investigate the recurrence rate and changes in quality of life after multimodal therapy. DESIGN, SETTING, AND PARTICIPANTS: A total of 33 patients with 42 auricle keloids (24 female and 9 male patients; mean [SD] age, 27 [17] years) were enrolled in a prospective cohort study and underwent intramarginal keloid excision and multimodal therapy. Patients were observed postoperatively in the outpatient Department of Otorhinolaryngology-Head and Neck Surgery, University Hospital of Mannheim, from August 1, 2007, through September 30, 2014, with a mean (SD) follow-up of 30 (19) months (through August 31, 2014). A retrospective analysis of clinical outcomes was performed from September 1 through November 15, 2014. INTERVENTIONS: Excision followed by 6 intralesional corticosteroid injections at 4- to 6-week intervals and individually customized pressure splints applied at least 5 nights a week for 6 months. MAIN OUTCOMES AND MEASURES: Keloid recurrence rate and subjective handling of the pressure splint were evaluated during clinical visits. Quality of life was measured after the end of therapy with a 3-part questionnaire, including the Glasgow Benefit Inventory (GBI). RESULTS: After excluding 4 patients (with 5 keloids) for nonadherence to treatment, 3 of 37 keloids recurred, for a recurrence rate of 8% among 29 patients. Insecure handling of the pressure splint significantly correlated with a higher relapse rate (mean subjective handling score in patients with a relapse, 3.60; P = .02). Four of 8 patients with recurrent keloids had poor adherence to adjuvant pressure therapy, which suggests an association between keloid recurrence and adherence to adjuvant pressure therapy. Patients received the 3 part questionnaire by mail to collect data on quality of life. Of 43 patients approached, 33 treated with multimodal therapy completed the questionnaire for a return rate of 77%. Improvement in quality of life after keloid treatment was significant in recurrence-free patients, with a mean GBI score of 22.53 (P < .001). CONCLUSIONS AND RELEVANCE: The present study showed an improvement in quality-of-life scores after multimodal therapy for keloids. Because poor adherence to the use of ear splints correlated with a higher recurrence rate of keloids, efforts are needed to improve adherence and minimize recurrence. LEVEL OF EVIDENCE: 3. PMID- 26270084 TI - Elucidating Nonwetting of Re-Entrant Surfaces with Impinging Droplets. AB - Superomniphobic surfaces display both superoleophobic and superhydrophobic properties, having a contact angle greater than 150 degrees for both water and oil droplets. In this work, lattice Boltzmann simulations on droplets impacting the surface textures of various topologies are performed to understand the mechanism of how the superomniphobic properties can be achieved by optimizing the geometry of re-entrant surfaces and the inherent hydrophobicity of substrates. Detailed kinetics for droplet impinging is analyzed for both liquid impalement and emptying, showing distinct dependences on geometrical details of re-entrant surfaces. The origins of the enhanced stability of Cassie states are ascribed to (i) the barrier of the Cassie-to-Wenzel transition for the impalement process, (ii) the driving force for liquid receding in the emptying process, and (iii) the contact line pinning from the entrance effect and the edge effect. Finally, we check the strategies proposed here by designing a new re-entrance structure that possesses an excellent property in maintaining the droplet Cassie state. PMID- 26270085 TI - The Wide-Range Method to Construct the Entire Coexistence Liquid-Gas Curve and to Determine the Critical Parameters of Metals. AB - A method to find the liquid-gas critical parameters of metallic elements is offered. It takes into account a nonanalytic behavior in the critical point vicinity and the Clapeyron-Clausius asymptotic behavior at low temperatures. The present approach provides good agreement with experimental data for a wide wealth of non-metallic substances and mercury and alkali metals, where the critical parameters and binodals are known from the measurements. We have also found the critical parameters and binodals for Al, Cu, Fe, and Zr, for which corresponding measurements are yet to be obtained. PMID- 26270086 TI - Second-Harmonic Generation from Sub-5 nm Gaps by Directed Self-Assembly of Nanoparticles onto Template-Stripped Gold Substrates. AB - Strong field enhancement and confinement in plasmonic nanostructures provide suitable conditions for nonlinear optics in ultracompact dimensions. Despite these enhancements, second-harmonic generation (SHG) is still inefficient due to the centrosymmetric crystal structure of the bulk metals used, e.g., Au and Ag. Taking advantage of symmetry breaking at the metal surface, one could greatly enhance SHG by engineering these metal surfaces in regions where the strong electric fields are localized. Here, we combine top-down lithography and bottom up self-assembly to lodge single rows of 8 nm diameter Au nanoparticles into trenches in a Au film. The resultant "double gap" structures increase the surface to-volume ratio of Au colocated with the strong fields in ~2 nm gaps to fully exploit the surface SHG of Au. Compared to a densely packed arrangement of AuNPs on a smooth Au film, the double gaps enhance SHG emission by 4200-fold to achieve an effective second-order susceptibility chi((2)) of 6.1 pm/V, making it comparable with typical nonlinear crystals. This patterning approach also allows for the scalable fabrication of smooth gold surfaces with sub-5 nm gaps and presents opportunities for optical frequency up-conversion in applications that require extreme miniaturization. PMID- 26270087 TI - Mapping the Evolution of Spatial Exciton Coherence through Time-Resolved Fluorescence. AB - Quantum coherence is expected to have a positive effect on the transfer efficiency of excitation energy through photosynthetic aggregates and conjugated polymers, but its significance to the functioning of these molecular assemblies remains largely unknown. We propose a new experimental means to monitor the coherence between distant molecular sites on a time scale relevant to energy transfer. Through numerical calculations, we demonstrate that the range of such spatial coherence continually scales as the 0-0 to 0-1 vibronic peak ratio in time-resolved fluorescence spectroscopy. As such, this observable allows one to monitor the coherent evolution of an excited state, displaying the large coherence length following optical excitation, and the subsequent dephasing over time. PMID- 26270088 TI - Anomalous Hysteresis in Perovskite Solar Cells. AB - Perovskite solar cells have rapidly risen to the forefront of emerging photovoltaic technologies, exhibiting rapidly rising efficiencies. This is likely to continue to rise, but in the development of these solar cells there are unusual characteristics that have arisen, specifically an anomalous hysteresis in the current-voltage curves. We identify this phenomenon and show some examples of factors that make the hysteresis more or less extreme. We also demonstrate stabilized power output under working conditions and suggest that this is a useful parameter to present, alongside the current-voltage scan derived power conversion efficiency. We hypothesize three possible origins of the effect and discuss its implications on device efficiency and future research directions. Understanding and resolving the hysteresis is essential for further progress and is likely to lead to a further step improvement in performance. PMID- 26270089 TI - Reactivity Descriptor in Solid Acid Catalysis: Predicting Turnover Frequencies for Propene Methylation in Zeotypes. AB - Recent work has reported the discovery of metal surface catalysts by employing a descriptor-based approach, establishing a correlation between a few well-defined properties of a material and its catalytic activity. This theoretical work aims for a similar approach in solid acid catalysis, focusing on the reaction between propene and methanol catalyzed by Bronsted acidic zeotype catalysts. Experimentally, the ammonia heat of adsorption is often used as a measure of the strength of acid sites. Using periodic DFT calculations, we show that this measure can be used to establish scaling relations for the energy of intermediates and transition states, effectively describing the reactivity of the acid site. This allows us to use microkinetic modeling to predict a quantitative relation between the ammonia heat of adsorption and the rate of propene methylation from first principles. We propose that this is the first step toward descriptor-based design of solid acid catalysts. PMID- 26270090 TI - Enhanced Water Splitting Efficiency Through Selective Surface State Removal. AB - Hematite (alpha-Fe2O3) thin film electrodes prepared by atomic layer deposition (ALD) were employed to photocatalytically oxidize water under 1 sun illumination. It was shown that annealing at 800 degrees C substantially improves the water oxidation efficiency of the ultrathin film hematite electrodes. The effect of high temperature treatment is shown to remove one of two surface states identified, which reduces recombination and Fermi level pinning. Further modification with Co-Pi water oxidation catalyst resulted in unprecedented photocurrent onset potential of ~0.6 V versus reversible hydrogen electrode (RHE; slightly positive of the flat band potential). PMID- 26270091 TI - Optically Guided Photoactivity: Coordinating Tautomerization, Photoisomerization, Inhomogeneity, and Reactive Intermediates within the RcaE Cyanobacteriochrome. AB - The RcaE cyanobacteriochrome uses a linear tetrapyrrole chromophore to sense the ratio of green and red light to enable the Fremyella diplosiphon cyanobacterium to control the expression of the photosynthetic infrastructure for efficient utilization of incident light. The femtosecond photodynamics of the embedded phycocyanobilin chromophore within RcaE were characterized with dispersed femtosecond pump-dump-probe spectroscopy, which resolved a complex interplay of excited-state proton transfer, photoisomerization, multilayered inhomogeneity, and reactive intermediates. These reactions were integrated within a central model that incorporated a rapid (200 fs) excited-state Le Chatelier redistribution between parallel evolving populations ascribed to different tautomers. Three photoproducts were resolved and originates from four independent subpopulations, each with different dump-induced behavior: Lumi-Go was depleted, Lumi-Gr was unaffected, and Lumi-Gf was enhanced. This suggests that RcaE may be engineered to act either as an in vivo fluorescent probe (after single-pump excitation) or as an in vivo optogenetic sample (after pump and dump excitation). PMID- 26270092 TI - How the Reorganization Free Energy Affects the Reduction Potential of Structurally Homologous Cytochromes. AB - Differences in the reduction potential E(0) among structurally similar metalloproteins cannot always be fully explained on the basis of their 3-D structures. We investigate the molecular determinants to E(0) using the mixed quantum mechanics/molecular mechanics approach named perturbed matrix method (PMM); after comparison with experimental values to assess the reliability of our calculations, we investigate the relationship between the change in free energy upon reduction DeltaA(0) and the reorganization energy. We find that the reduction potential of cytochromes can be regarded as the result of the sum of two terms, one being mostly dependent on the energy fluctuations within a limited range around the mean transition energy and the second being mostly dependent linearly on the difference Deltalambda = lambdared - lambdaox of the reorganization free energies for the ox -> red (lambdared) and for the red -> ox (lambdaox) relaxations. PMID- 26270093 TI - Ultrafast Structure and Dynamics in Ionic Liquids: 2D-IR Spectroscopy Probes the Molecular Origin of Viscosity. PMID- 26270094 TI - X-ray Absorption Spectra of Dissolved Polysulfides in Lithium-Sulfur Batteries from First-Principles. AB - The X-ray absorption spectra (XAS) of lithium polysulfides (Li2Sx) of various chain lengths (x) dissolved in a model solvent are obtained from first-principles calculations. The spectra exhibit two main absorption features near the sulfur K edge, which are unambiguously interpreted as a pre-edge near 2471 eV due to the terminal sulfur atoms at either end of the linear polysulfide dianions and a main edge near 2473 eV due to the (x - 2) internal atoms in the chain, except in the case of Li2S2, which only has a low-energy feature. We find an almost linear dependence between the ratio of the peaks and chain length, although the linear dependence is modified by the delocalized, molecular nature of the core-excited states that can span up to six neighboring sulfur atoms. Thus, our results indicate that the ratio of the peak area, and not the peak intensities, should be used when attempting to differentiate the polysulfides from XAS. PMID- 26270095 TI - Interaction of NH3 with Cu-SSZ-13 Catalyst: A Complementary FTIR, XANES, and XES Study. AB - In the typical NH3-SCR temperature range (100-500 degrees C), ammonia is one of the main adsorbed species on acidic sites of Cu-SSZ-13 catalyst. Therefore, the study of adsorbed ammonia at high temperature is a key step for the understanding of its role in the NH3-SCR catalytic cycle. We employed different spectroscopic techniques to investigate the nature of the different complexes occurring upon NH3 interaction. In particular, FTIR spectroscopy revealed the formation of different NH3 species, that is, (i) NH3 bonded to copper centers, (ii) NH3 bonded to Bronsted sites, and (iii) NH4(+).nNH3 associations. XANES and XES spectroscopy allowed us to get an insight into the geometry and electronic structure of Cu centers upon NH3 adsorption, revealing for the first time in Cu-SSZ-13 the presence of linear Cu(+) species in Ofw-Cu-NH3 or H3N-Cu-NH3 configuration. PMID- 26270096 TI - Visible-Range Sensitization of Er(3+)-Based Infrared Emission from Perfluorinated 2-Acylphenoxide Complexes. AB - Five new fully fluorinated acylphenoxide ligands, which are aromatic analogues of beta-diketonates, provide visible photosensitization of the Er(3+4)I13/2 -> (4)I15/2 emission at ~1540 nm (of interest for telecommunications) via the "antenna effect", as observed in Cs[ErL4] compounds. Depending on the chemical functionalization, the excitation wavelength can be tuned in the 400-650 nm range. Decay times for the solids are in the range of 7-16 MUs, proving that the complexes can be of interest for a number of optoelectronic and photonic applications. PMID- 26270097 TI - Defect Chemistry and Plasmon Physics of Colloidal Metal Oxide Nanocrystals. AB - Plasmonic nanocrystals of highly doped metal oxides have seen rapid development in the past decade and represent a class of materials with unique optoelectronic properties. In this Perspective, we discuss doping mechanisms in metal oxides and the accompanying physics of free carrier scattering, both of which have implications in determining the properties of localized surface plasmon resonances (LSPRs) in these nanocrystals. The balance between activation and compensation of dopants limits the free carrier concentration of the most common metal oxides, placing a ceiling on the LSPR frequency. Furthermore, because of ionized impurity scattering of the oscillating plasma by dopant ions, scattering must be treated in a fundamentally different way in semiconductor metal oxide materials when compared with conventional metals. Though these effects are well understood in bulk metal oxides, further study is needed to understand their manifestation in nanocrystals and corresponding impact on plasmonic properties, and to develop materials that surpass current limitations in free carrier concentration. PMID- 26270098 TI - How Does a SILAR CdSe Film Grow? Tuning the Deposition Steps to Suppress Interfacial Charge Recombination in Solar Cells. AB - Successive ionic layer adsorption and reaction (SILAR) is a popular method of depositing the metal chalcogenide semiconductor layer on the mesoscopic metal oxide films for designing quantum-dot-sensitized solar cells (QDSSCs) or extremely thin absorber (ETA) solar cells. While this deposition method exhibits higher loading of the light-absorbing semiconductor layer than direct adsorption of presynthesized colloidal quantum dots, the chemical identity of these nanostructures and the evolution of interfacial structure are poorly understood. We have now analyzed step-by-step SILAR deposition of CdSe films on mesoscopic TiO2 nanoparticle films using X-ray absorption near-edge structure analysis and probed the interfacial structure of these films. The film characteristics interestingly show dependence on the order in which the Cd and Se are deposited, and the CdSe-TiO2 interface is affected only during the first few cycles of deposition. Development of a SeO2 passivation layer in the SILAR-prepared films to form a TiO2/SeO2/CdSe junction facilitates an increase in photocurrents and power conversion efficiencies of quantum dot solar cells when these films are integrated as photoanodes in a photoelectrochemical solar cell. PMID- 26270099 TI - Designing Plasmon Resonances. PMID- 26270100 TI - CO Oxidation Promoted by Gold Atoms Loosely Attached in AuFeO3(-) Cluster Anions. AB - Time-of-flight mass spectrometry experiment shows that upon the interactions with carbon monoxide, the mass-selected AuFeO3(-) oxide cluster anions can evaporate neutral gold atoms in a hexapole collision cell and oxidize CO into CO2 in an ion trap reactor. The computational studies identify that the gold atom is loosely attached in the AuFeO3(-) cluster, and the different reaction channels can be attributed to different cluster velocities. The structure of the AuFeO3(-) cluster is very flexible, and the approach of CO induces significant geometrical and electronic structure changes of AuFeO3(-), which facilitates the exposure of the positively charged gold atom to trap and oxidize CO. The CO oxidation by the AuFeO3(-) cluster follows the Au-assisted Mars-van Krevelen mechanism, in which the direct participation of the surface lattice oxygen (O(2-)) is proposed. PMID- 26270101 TI - Halogen-Halogen Links and Internal Dynamics in Adducts of Freons. AB - The pulsed jet Fourier transform microwave spectrum of the 1:1 complex between CF3Cl and CH3F shows that the two moieties are linked by a Cl...F halogen bond (RCl...F = 2.995 A). The two symmetric tops CF3 and CH3 undergo free or almost free internal rotations, which alter the "rigid" value of the rotational constant A by almost 1 order of magnitude. PMID- 26270102 TI - PtZnH5(-), A sigma-Aromatic Cluster. AB - We report a joint photoelectron spectroscopic and theoretical study of the PtZnH5(-) cluster anion. This cluster exhibited an unprecedented planar pentagonal coordination for Pt and an unusual stability and high intensity in the mass spectrum. Both are due to the sigma-aromaticity found in the H5-cycle supported by the 5d orbitals on the Pt atom. sigma-Aromaticity in all-H systems has been predicted in the past but never found in experimentally observed species. Besides fundamental importance, mixed transition-metal hydrides can be found as intermediates in catalytic processes, and thus, the unexpected stability facilitated by sigma-aromaticity can be appreciated also in practical applications. PMID- 26270103 TI - Effects of Graphene Nanopore Geometry on DNA Sequencing. AB - In this Letter we assess the effect of graphene nanopore geometries on DNA sequencing by considering DNA fragments including A, T, C, G, and 5 methylcytosine (MC) pulled out of graphene nanopores of different geometries with diameters down to ~1 nm. Using steered molecular dynamics simulations it is demonstrated that the bases (A, T, C, G, and MC) can be indentified at single base resolution through the characteristic peaks on the force profile in a circular graphene nanopore but not in nanopores with other asymmetric geometries. Our study suggests that the graphene nanopore surface should be modified as symmetrically as possible in order to sequence DNA by atomic force microscopy or optical tweezers. PMID- 26270104 TI - Self-Assembly of Supramolecular Light-Harvesting Arrays from Symmetric Perylene 3,4-dicarboximide Trefoils. AB - Unlike the widely studied perylene-3,4:9,10-bis(dicarboximide) (PDI) dyes, self assembly of the corresponding perylene-3,4-dicarboximide (PMI) dyes into large arrays and studies of their excited state properties have received far less attention. Two symmetric PMI trefoils were synthesized by connecting the 9 position of the perylene core either directly (1) or through a phenylene linker (2) to the 1,3,5-positions of a central benzene ring. Synchrotron-based small- and wide-angle X-ray scattering measurements in methylcyclohexane show that trefoil 1 self-assembles into cofacial trimers (13) on average, while trefoil 2 forms much larger assemblies that are tridecamers (213) on average. Their photophysics were characterized using steady-state as well as transient absorption and emission spectroscopy. Time-resolved spectroscopy reveals that both 13 and 213 initially form excitonically coupled excited states that subsequently relax to excimer states having 20 and 8.4 ns lifetimes, respectively, which decay to ground-state primarily nonradiatively. The data are consistent with stronger electronic coupling between the PMI molecules in 213 relative to 13. PMID- 26270105 TI - Mechanism of the Decay of Thymine Triplets in DNA Single Strands. AB - The decay of triplet states and the formation of cyclobutane pyrimidine dimers (CPDs) after UV excitation of the all-thymine oligomer (dT)18 and the locked dinucleotide TLpTL were studied by nanosecond IR spectroscopy. IR marker bands characteristic for the CPD lesion and the triplet state were observed from ~1 ns (time resolution of the setup) onward. The amplitudes of the CPD marker bands remain constant throughout the time range covered (up to 10 MUs). The triplet decays with a time constant of ~10 ns presumably via a biradical intermediate (lifetime ~60 ns). This biradical has often been invoked as an intermediate for CPD formation via the triplet channel. The present results lend strong support to the existence of this intermediate, yet there is no indication that its decay contributes significantly to CPD formation. PMID- 26270106 TI - Insights into the Unexpected Chemoselectivity for the N-Heterocyclic Carbene Catalyzed Annulation Reaction of Allenals with Chalcones. AB - Lewis base N-heterocyclic carbene (NHC)-catalyzed annulation is the subject of extensive interest in synthetic chemistry, but the reaction mechanisms, especially the unexpected chemoselectivity of some of these reactions, are poorly understood. In this work, a systematic theoretical calculation has been performed on NHC-catalyzed annulation between allenals and chalcone. Multiple possible reaction pathways (A-E) leading to three different products have been characterized. The calculated results reveal that NHC is more likely to initiate the reaction by nucleophilic attack on the center carbon atom of the allene group but not the carbonyl carbon atom in allenals leading to the Breslow intermediate, which is remarkably different from the other NHC-catalyzed annulations of unsaturated aldehydes with chalcones. The computed energy profiles demonstrate that the most energetically favorable pathway (A) results in polysubstituted pyranyl aldehydes, which reasonably explains the observed chemoselectivity in the experiment. The observed chemoselectivity is demonstrated to be thermodynamically but not kinetically controlled, and the stability of the Breslow intermediate is the key for the possibility of homoenolate pathway D and enolate pathway E. This work can improve our understanding of the multiple competing pathways for NHC catalyzed annulation reactions of unsaturated aldehydes with chalcones and provide valuable insights for predicting the chemoselectivity for this kind of reaction. PMID- 26270107 TI - Total Synthesis of (+)-Cryptocaryol A Using a Prins Cyclization/Reductive Cleavage Sequence. AB - The total synthesis of (+)-cryptocaryol A was achieved in 20 steps from (R) glycidol. The key steps were a Prins cyclization/reductive cleavage sequence to construct the C5-C11 polyol fragment, a diastereoselective aldol reaction to control the stereogenic center at C13, and a stereocontrolled reduction to introduce the stereogenic center at C15. PMID- 26270108 TI - Problem-Based Learning in Prenursing Courses. AB - We conducted an observational study with 150 undergraduate nursing students to verify the usefulness of problem-based learning in the classroom and to ascertain whether this methodology facilitated the development of their knowledge acquisition skills. Problem-based learning fostered the development of integrated knowledge acquisition skills among nursing students. PMID- 26270109 TI - Improving Adjunct Nursing Instructors' Knowledge of Student Assessment in Clinical Courses. AB - Utilization of adjunct nursing instructors to teach clinical courses is common in nursing programs. The purpose of this study was to examine the outcomes of a faculty development workshop on clinical evaluation for adjunct instructors. The results indicated instructors valued using a student-oriented learning outline, gained knowledge about assessment, and indicated they would engage in activities that could increase their knowledge of assessment. PMID- 26270110 TI - Use of Technology in Classroom Testing. PMID- 26270111 TI - Individualizing factor replacement therapy in severe hemophilia. AB - Prophylactic replacement of factor concentrate is the established optimal treatment to avoid or minimize joint disease in severe hemophilia patients, thus ultimately improving their life expectancy and quality of life toward values matching those in the normal population. Where uncertainty still exists is around the optimal regimen to be prescribed for prophylaxis, and more and more treaters and patients are showing interest in patient tailored approaches to prophylaxis, aiming at matching the prophylaxis regimen to the specific needs of the patient. The rationale behind tailoring the prophylaxis regimen to the individual patient is based on the significant variability that exists between patients (all with the same label of severe hemophilia) with respect to their bleeding phenotype, their pharmacokinetic handling of factor, their levels of physical activity, and a variety of other characteristics that contribute to differential prophylaxis needs of patients. Of course, any form of tailoring of prophylaxis needs to take into consideration the economic resources of the country; for many countries very intense prophylaxis regimens are just not possible. This article will review different concerns and strategies when tailoring prophylaxis, and will address how these issues will apply to the new longer acting factor concentrates in development. PMID- 26270112 TI - Homeostasis of Hemostasis: The Role of Endothelium. AB - Forming an interface with virtually every other organ, endothelium has a strategic role in modulating vascular homeostasis. While its miscellany of functions includes regulation of vasomotor tone, promotion, and prevention of vascular growth, and modulation of inflammatory and hemostatic processes, it functions critically in maintaining the balance of hemostasis in health. Whereas endothelium has been recognized to influence all stages of hemostasis, new evidence suggests it to have a primary role for thrombin generation. Endothelial dysfunction is being increasingly appreciated in several pathological states and particularly, by virtue of its critical role in hemostasis, in causing thrombosis in a multitude of diseases. PMID- 26270113 TI - Hypercoagulability and Platelet Abnormalities in Inflammatory Bowel Disease. AB - Patients with inflammatory bowel disease (IBD) exhibit a threefold higher risk for development of systemic thrombosis than the general population. Although the underlying causes of the increased risk for thrombus development remain poorly understood, there is a large body of evidence suggesting that abnormalities in coagulation, fibrinolysis, and platelet function may contribute to this response. Changes in hemostatic biomarkers are consistent with subclinical activation of coagulation system, including tissue factor activation, impaired protein C pathway, enhanced thrombin generation, and diminished fibrinolytic capacity. There is also evidence for an increased production and reactivity of platelets, with an enhanced formation of platelet-platelet and platelet-leukocyte aggregates. The altered coagulation and platelet function, and the predisposition to thrombus formation have also been demonstrated in animal models of IBD. The animal studies have revealed a major role for inflammatory cytokines, including tumor necrosis factor-alpha, interleukin (IL)-1beta, and IL-6, as mediators of the platelet abnormalities and enhanced thrombus development in experimental IBD. These findings in animal models raise hope for the development of novel therapeutic strategies to reduce thrombosis-related mortality in IBD patients. PMID- 26270114 TI - Performance of the BD CTQx and GCQx Amplified Assays on the BD Viper LT Compared With the BD Viper XTR System. AB - We evaluated the BD Viper LT System for detection of Chlamydia trachomatis and Neisseria gonorrhoeae using samples collected from symptomatic patients that included urine, vaginal swabs, and cervical samples in liquid-based cytology media. Results were compared with those obtained using the BD Viper XTR platform. The positive and negative percent agreements for all sample types were at least 95.8% and at least 96.4% for chlamydia and gonorrhea and at least 95.0% when both organisms were present, respectively. This medium throughput system performs well compared with a high-throughput platform and may offer smaller health care facilities the opportunity to test for these infections locally. PMID- 26270115 TI - Conventional Landmark-Guided Midline Versus Preprocedure Ultrasound-Guided Paramedian Techniques in Spinal Anesthesia. AB - BACKGROUND: Multiple passes and attempts while administering spinal anesthesia are associated with a greater incidence of postdural puncture headache, paraesthesia, and spinal hematoma. We hypothesized that the routine use of a preprocedural ultrasound-guided paramedian technique for spinal anesthesia would reduce the number of passes required to achieve entry into the subarachnoid space when compared with the conventional landmark-guided midline approach. METHODS: One hundred consenting patients scheduled for elective total joint replacements (hip and knee) were randomized into group C (conventional) and group P (preprocedural ultrasound-guided paramedian technique) with 50 in each group. The patients were blinded to the study group. All spinal anesthetics were administered by a consultant anesthesiologist. In group C, spinal anesthetic was done via the midline approach using clinically palpated landmarks. In group P, a preprocedural ultrasound scan was used to mark the paramedian insertion site, and spinal anesthetic was performed via the paramedian approach. RESULTS: The average number of passes (defined as the number of forward advancements of the spinal needle in a given interspinous space, i.e., withdrawal and redirection of spinal needle without exiting the skin) in group P was approximately 0.34 times that in group C, a difference that was statistically significant (P = 0.01). Similarly, the average number of attempts (defined as the number of times the spinal needle was withdrawn from the skin and reinserted) in group P was approximately 0.25 times that of group C (P = 0.0021). In group P, on an average, it took 81.5 (99% confidence interval, 68.4-97 seconds) seconds longer to identify the landmarks than in group C (P = 0.0002). All other parameters, including grading of palpated landmarks, time taken for spinal anesthetic injection, periprocedural pain scores, periprocedural patient discomfort visual analog scale score, conversion to general anesthetic, paresthesia, and radicular pain during needle insertion, were similar between the 2 groups. CONCLUSIONS: Routine use of paramedian spinal anesthesia in the orthopedic patient population undergoing joint replacement surgery, guided by preprocedure ultrasound examination, significantly decreases the number of passes and attempts needed to enter the subarachnoid space. PMID- 26270116 TI - Extraperitoneal Para-aortic Lymphadenectomy by Robot-Assisted Laparoscopy in Gynecologic Oncology: Preliminary Experience and Advantages and Limitations. AB - BACKGROUND: We are reporting the preliminary multicentric experience in extraperitoneal para-aortic lymphadenectomy by robot-assisted laparoscopy (EPLRL) in gynecologic oncology. MATERIALS AND METHODS: Two teams from the cancer centers performed EPLRL in 37 patients with gynecologic cancer. RESULTS: There were 30 patients with cervical cancer, 6 with endometrial cancer, and 1 with adnexal cancer. The skin-to-skin operative time, mean lymph node count, and estimated blood loss were 221 (+/-61) minutes, 18.7 (+/-11), and 105 (+/-134) mL.There was no conversion to laparotomy, one laparoscopic conversion for hemorrhage lateral to the inferior mesenteric artery, and one use of hemostatic matrix for an injury to the left gonadal artery (2 nontransfused patients). The proportion of patients who reported postoperative complications was 32.5% (12/37): 7 with lymphocysts with computed tomographic scan drainage (19%), 3 with leg dysesthesia (left genitofemoral nerve), 1 with leg lymphedema, and 1 with lateral aortic hematoma not requiring a transfusion or return to the operating room. CONCLUSION: The EPLRL technique is feasible and efficient but with a high rate of symptomatic lymphocyst. A marsupialization could be useful to decrease the risk of lymphocyst. PMID- 26270117 TI - Hand-Assisted Robotic Surgery for Staging of Ovarian Cancer and Uterine Cancers With High Risk of Peritoneal Spread: A Retrospective Cohort Study. AB - OBJECTIVE: This study aimed to determine surgical outcomes related to hand assisted robotic surgery (HARS) for staging of ovarian cancer and uterine cancers with high risk of peritoneal spread and compare them to laparotomy and standard robotic-assisted surgery. METHODS: A retrospective cohort study of women undergoing staging for uterine and ovarian cancer between January 2011 and July 2013 at a major metropolitan teaching hospital was reviewed. Patients undergoing HARS were matched with patients undergoing staging laparotomy [exploratory laparotomy (XLAP)] for the same indications and with patients undergoing traditional robotic surgery (RS) for staging of endometrioid endometrial cancer. In HARS, a longer incision is used to allow palpation of the peritoneal surfaces, to exteriorize the small bowel, to examine the mesentery, and to perform omentectomy. RESULTS: One hundred five patients were analyzed (15 HARS, 45 RS, 45 XLAP). Compared with XLAP, HARS was associated with decreased blood loss (200 vs 400 mL, P = 0.011) and shorter hospital stay (1 vs 4 days, P < 0.001). Patients who had undergone HARS had fewer major complications, but those results did not reach statistical significance (0% vs 27%, P = 0.063). Hand-assisted robotic surgery was associated with higher blood loss and length of stay as compared to robotic staging of endometrioid endometrial cancer (RS). Minor wound complications were also more common (27% vs 2%, P = 0.012). CONCLUSIONS: Hand assisted robotic surgery allows for thorough visual and tactile assessment of peritoneal surfaces. It represents a safe alternative to laparotomy for staging of ovarian and uterine cancers with high risk of peritoneal spread. Long-term follow-up study is needed to determine oncologic adequacy of HARS. PMID- 26270118 TI - Gene Polymorphisms of Toll-Like Receptor 9 -1486T/C and 2848G/A in Cervical Cancer Risk. AB - OBJECTIVE: This work aims to explore whether Toll-like receptor 9 (TLR9) -1486T/C and 2848G/A polymorphisms are associated with cervical cancer risk. METHODS: A comprehensive electronic search of studies published from January 1999 to October 2014 was conducted in Medline (Ovid), Embase, PubMed, Wanfang, Weipu, and CNKI. The algorithm included "TLR," "Toll-like receptor," "polymorphism," "variant," "mutation," and "cervical cancer." Seven articles, including 9 studies, were pooled using Revman 5.2 (Cochrane Collaboration, Copenhagen, Denmark). Odds ratio (OR) was used to explore the involvement of minor allele C (C vs T and CC + CT vs TT) of TLR9 (-1486T/C, rs187084) and minor allele A (A vs G and AA + AG vs GG) of TLR9 (2848G/A, rs352140) in cervical cancer risk. RESULTS: Toll-like receptor 9 ( 1486T/C, rs187084) polymorphisms were associated with an elevated risk of cervical cancer (C vs T: OR, 1.15; 95% confidence interval [CI], 1.03-1.29; CC + CT vs TT: OR, 1.30; 95% CI, 1.11-1.53). We found no significant association between TLR9 (2848G/A, rs352140) polymorphisms and cervical cancer risk (A vs G: OR, 1.15; 95% CI, 0.87-1.54; AA + AG vs GG: OR, 1.27; 95% CI, 0.75-2.17). CONCLUSIONS: This meta-analysis indicates that TLR9 (-1486T/C, rs187084)-but not TLR9 (2848G/A, rs352140)-may be a risk factor for cervical cancer. PMID- 26270119 TI - Economic Impact Among Family Caregivers of Patients With Advanced Ovarian Cancer. AB - OBJECTIVES: The life of a family caregiver changes in many ways when cancer is diagnosed. Changes regard also financial costs. To the authors' knowledge, little work has been done to estimate the costs associated with caregiving for cancer patients. The aim of the present study is to evaluate for the first time in literature the economic changes among family caregivers of advanced ovarian cancer during the first-line treatment in an Italian survey. METHODS: Between January 2009 and June 2014, the primary family caregivers of patients with advanced ovarian cancer (N = 172) were recruited from to the Division of Gynecologic Oncology of the University Campus Bio-Medico of Rome within 4 weeks of the patient's new diagnosis. Caregivers reported demographic, medical information, and economic cost, such as traveling to and from medical appointments, waiting with patients for appointments, missing work, and attending to patients who are hospitalized. RESULTS: Between January 2009 and June 2014, 172 primary family caregivers of patients with advanced ovarian cancer were enrolled in the study. The mean age of the study cohort was 54.01 years. They reported 3% of missing workdays. The mean cost for all caregivers was &OV0556;1,888,732 per year. Therefore, the mean cost for each caregiver was &OV0556;10,981 annually. CONCLUSIONS: This economic analysis of caregiving in patients with advanced ovarian cancer reports the significant burden that cancer treatment places on both families and society. These findings underscore the importance, when appropriate, of including valid estimates of the cost of informal caregiving when evaluating the cost-effectiveness of cancer treatments. PMID- 26270120 TI - Relative Morbidity and Mortality of Panniculectomy-Combined Surgical Staging in Endometrial Cancer. AB - OBJECTIVE: To examine intraoperative and postoperative complication rates for surgical staging combined with panniculectomy for endometrial cancer. METHODS: A prospectively collected institutional surgical database was used to identify patients with endometrial cancer who underwent hysterectomy-based surgical staging between December 2008 and August 2014 (n = 551). The cases were grouped into surgical staging with panniculectomy (panniculectomy group, n = 11 [2.0%]), laparotomy without panniculectomy (laparotomy group, n = 208 [37.7%]), and laparoscopy (minimally invasive surgery group, n = 332 [60.3%]). Major complication and surgical wound complication rates within 30 days from surgery were compared. RESULTS: The panniculectomy group had a significantly higher body mass index compared with other approaches (panniculectomy group, laparotomy group, and minimally invasive surgery group: 60.4, 35.7, and 34.1; P < 0.001) and had a high stage I disease rate (90.9%, 61.5%, and 88.3%; P < 0.001). Mean pannus weight was 5733 g (4.4% of body weight). Intraoperative major complication rates were statistically nonsignificant across the groups (0%, 7.2%, and 4.2%; P = 0.23); however, the panniculectomy group had a significantly higher postoperative major complication rate compared with other approaches (36.4%, 16.3%, and 5.1%; P < 0.001). In multivariate analysis controlling for age, ethnicity, body habitus, medical comorbidities, and tumor factors, panniculectomy remained an independent predictor for increased risk of postoperative major complications (adjusted odds ratio, 4.37; P = 0.043). Surgical mortality rates were similar across the groups (0%, 0.5%, and 0%; P = 0.44). Among superobese patients (n = 50), intraoperative and postoperative complication rates were statistically similar across the 3 groups (all, P > 0.05). CONCLUSION: Although panniculectomy-combined surgical staging is associated with an increased risk of postoperative complications, the majority recovered uneventfully, making this approach a feasible treatment option, especially for superobese patients with endometrial cancer. PMID- 26270121 TI - Interleukin-28B Plays a Therapeutic Role on Mouse U14 Cervical Cancer Cells by Down-Regulating CD4+CD25+FoxP3+Regulatory T Cells In Vivo. AB - AIM: To investigate the immunotherapeutic effectiveness of adenoviral vector expressing mouse interleukin (IL)-28B (Ad-mIL-28B) against cervical cancer and its mechanism. METHOD: U14 cervical cancer cell-bearing mice were treated with Ad mIL-28B. Meanwhile, whole cell vaccine was prepared by repeated freezing and thawing U14 cells. Then CD4+CD25+FoxP3+regulatory T (Treg) cells were evaluated by flow cytometry. Tumor volume and metastasis in BALB/c and C57BL/6j mice were detected. RESULTS: Ad-mIL-28B treatment significantly decreased the number of CD4+CD25+FoxP3+Treg cells. Subsequently, there was a significant decrease in the size of tumor tissue and the numbers of heteromorphic tumor cells. The tumor metastasis in the lung and liver of the Ad-mIL-28B group also decreased. However, there was no therapeutic effect observed for whole cell vaccine on U14 tumor bearing mice. CONCLUSION: Interleukin-28B can inhibit the growth and metastasis of cervical cancer in U14 tumor-bearing mice by down-regulating Treg cells. PMID- 26270122 TI - The Role of Computed Tomography Scanning of the Thorax in the Initial Assessment of Gestational Trophoblastic Neoplasia. AB - OBJECTIVE: The aim of this study was to determine whether lesions found on computed tomography (CT) imaging of the thorax would affect FIGO (International Federation of Gynecology and Obstetrics) 2000 risk score and/or alter clinical management. METHODS: The Sheffield Trophoblastic Disease database was searched for all new patients registered for staging/scoring investigations between January 1, 2006, and June 30, 2010. The FIGO 2000 score was noted and then recalculated using information from CT scan reports. Where a change of risk score would have affected a patient's management, the case notes were further reviewed. RESULTS: 191 patients had undergone both modalities of imaging. Using standard FIGO scoring, 169 and 22 patients were noted to be at low and high risk, respectively. Using information from CT imaging, only a further 20 patients would have been reclassified as high risk. Fifteen of these "new" high-risk patients required salvage treatment with intravenous chemotherapy; all were cured. CONCLUSIONS: With no potential advantage in terms of patient outcome and significantly increased radiation dose, there is little justification for routine CT imaging of the thorax in the initial assessment of new patients with gestational trophoblastic neoplasia. PMID- 26270123 TI - Treatment Compliance and Outcomes for Women With Locoregionally Advanced Cervical Cancer Treated in a Safety Net Health System. AB - OBJECTIVE: This study aims to assess treatment compliance among women undergoing definitive chemoradiation with weekly cisplatin for cervical cancer within a safety net health system and to quantify the impact of chemotherapy compliance on outcomes. MATERIALS AND METHODS: All women who were treated for International Federation of Gynecology and Obstetrics stage IB2 to stage IVA cervical cancer between April 2008 and May 2014 were identified. Treatment delays were attributed to toxicity, comorbid conditions, or system issues, or categorized as patient initiated. Disease-free survival and overall survival of women who received fewer than 6 versus 6 or more doses of weekly cisplatin 40 mg/m were compared using Kaplan-Meier analyses. RESULTS: One hundred nineteen women (mean [SD] age, 48.5 [11.8] years) were identified. Most women (n = 112; 94.1%) completed definitive radiotherapy, requiring a mean (SD) of 56.5 (20.1) days. Sixty-four women (57.1%) completed definitive radiotherapy in 56 days or less. Only 44 women (36.4%) received 6 or more cycles of cisplatin. Of 122 delayed cycles, reasons for delay were as follows: grade 2 or higher toxicity (n = 70; 57.4%), medical comorbidity (n = 12; 9.8%), system issues (n = 9; 7.4%), and patient-initiated (n = 14; 11.5%). Multiple issues complicated treatment for 3 doses (2.5%). Reasons for delay were not documented in 14 doses (11.5%). Among patients who received 6 or more cycles, disease-free survival improved by 17.4 months (mean [SD], 61.1 [3.7] vs 43.7 [4.3] months, P = 0.002) and overall survival improved by 8.6 months (mean [SD], 68.7 [2.3] vs 60.1 [3.7] months, P = 0.011). CONCLUSIONS: Higher rates of toxicity and psychosocial barriers to chemotherapy compliance adversely impact survival among women who seek care in low-resource settings. In our population, administration of all 6 cycles of cisplatin was necessary for optimal survival benefit. Future efforts to improve cervical cancer outcomes should address preventable reasons for treatment delays among underinsured or uninsured individuals. PMID- 26270124 TI - Location of Sentinel Lymph Node in Cervical Carcinoma and Factors Associated With Unilateral Detection. AB - OBJECTIVE: The aims of this study were to assess locality of the sentinel lymph node (SLN) in cervical carcinoma and examine factors affecting bilateral SLN detection. METHODS: This was a retrospective review of SLN data (anatomical location, count and laterality) in patients with early-stage cervical cancer (International Federation of Gynecology and Obstetrics stage IA1 with lymphovascular space invasion to stage IIA) using intraoperative gamma probe and blue dye. The preoperative single-photon emission computed tomography with computed tomography was used to detect laterality, number of the SLNs, and rare locations. Patients were treated between January 2005 to January 2015 at the West Kent Gynaecological Oncology Centre, Maidstone Hospital, Maidstone, United Kingdom. RESULTS: A total of 132 women were investigated. The most common SLN location was the external iliac (38.6%) followed by obturator (25.3%) and internal iliac (23.6%) regions. A small percentage was identified in presacral (1.4%) and para-aortic regions (0.7%). Older age (P = 0.01) and an elevated body mass index (P = 0.03) were associated with decreased SLN count by preoperative single-photon emission computed tomography with computed tomography, and only age affected SLN count by gamma probe (P = 0.01). Initial surgery, large loop excision of the transformation zone, or cone biopsy of the cervix had no effect on SLN count. There was no difference observed in bilateral detection with respect to surgical approach (open: n = 48/laparoscopic: n = 84). However, older age was independently associated with a decrease in bilateral SLN detection (P = 0.003). In these patients who underwent unilateral full pelvic lymphadenectomy, all the nonsentinel nodes were negative. CONCLUSIONS: The majority of SLNs were located in the external iliac, obturator, and internal iliac regions. Both older age and an elevated body mass index were associated with a reduced SLN count. Unilateral detection of SLN was independently associated with older age, which may be due to sclerosis in the lymphatic vessels or reduced perfusion in the pelvis in these women. If no SLN is detected on one side, the consensus is to perform a full pelvic lymphadenectomy on that side of the pelvis. PMID- 26270126 TI - A Quasiclassical Study of the F((2)P) + CHD3 (nu1 = 0,1) Reactive System on an Accurate Potential Energy Surface. AB - Quasiclassical trajectories (QCT) have been employed to elucidate the effect of exciting the C-H bond in F + CHD3 collisions. The calculations were performed on a new potential energy surface that accurately describes the van der Waals complexes in the entrance channel of the reaction. It was found that exciting the C-H bond significantly enhances the yield of HF + CD3, whereas it has a minor effect on the production of DF + CHD2. Therefore, the net effect is that the total reactivity increases upon excitation. This result strongly contradicts recent experimental findings. Significant differences in regard to the yield of each product channel were also found between QCT results calculated with the new surface and those obtained with the surface previously developed by Czako et al. This shows that relatively small variations in the topography of the entrance channel can result in huge discrepancies in the predicted DF/HF branching ratio. However, in regard to other attributes of the reaction, the agreement between QCT results computed with different surfaces, and between them and experimental results, is good. For the F + CHD3 -> HF + CD3 reaction, at a collisional energy of 9.0 kcal/mol, experiments and QCT calculations agree, indicating that the extra energy deposited in the C-H bond is channelled into the HF product. In addition, the angular distribution of CD3 is backward oriented and is not sensitive to the excitation of the C-H bond. PMID- 26270125 TI - Cherenkov radiation fluence estimates in tissue for molecular imaging and therapy applications. AB - Cherenkov radiation has recently emerged as an interesting phenomenon for a number of applications in the biomedical sciences. Its unique properties, including broadband emission spectrum, spectral weight in the ultraviolet and blue wavebands, and local generation of light within a given tissue, have made it an attractive new source of light within tissue for molecular imaging and phototherapy applications. While several studies have investigated the total Cherenkov light yield from radionuclides in units of [photons/decay], further consideration of the light propagation in tissue is necessary to fully consider the utility of this signal in vivo. Therefore, to help further guide the development of this novel field, quantitative estimates of the light fluence rate of Cherenkov radiation from both radionuclides and radiotherapy beams in a biological tissue are presented for the first time. Using Monte Carlo simulations, these values were found to be on the order of 0.01-1 nW cm(-2) per MBq g(-1) for radionuclides, and 1-100 MUW cm(-2) per Gy s(-1) for external radiotherapy beams, dependent on the given waveband, optical properties, and radiation source. For phototherapy applications, the total light fluence was found to be on the order of nJ cm(-2) for radionuclides, and mJ cm(-2) for radiotherapy beams. The results indicate that diagnostic potential is reasonable for Cherenkov excitation of molecular probes, but phototherapy may remain elusive at such exceedingly low fluence values. The results of this study are publicly available for distribution online at www.dartmouth.edu/optmed/. PMID- 26270128 TI - Near-IR Electrochromic Film Prepared by Oxidative Electropolymerization of the Cyclometalated Pt(II) Chloride with a Triphenylamine Group. AB - A cyclometalated platinum chloride [(L)PtCl] {L = 4-[p-(diphenylamino)phenyl]-6 phenyl-2,2'-bipyridine} was successfully synthesized and characterized by (1)H NMR, (13)C NMR, MALDI-TOF MS, elemental analysis, and X-ray crystallography. Its oxidative electropolymerization proceeds smoothly on the working Pt and ITO electrodes by cyclic voltammetry. The film thickness can be easily tuned by controlling the CV scan number. The orange hybrid polymer film shows the nondiffusion-controlled redox processes and a unusually inverse dependence of ac impedance on its thickness. As a result of switching of the MLCT/ICT and dication absorption transitions, the adherent metallopolymer film exhibits the low-voltage controlled anodic coloration near-IR electrochromism with significant optical contrast ratio (DeltaT% = 88.8% at 820 nm), fast response time (1.9 s for the coloration step and 2.3 s for the bleaching step), and high coloration efficiency (CE = 363.3 C(-1).cm(2)). PMID- 26270129 TI - Microleakage of Self-Etch Adhesive System in Class V Cavities Prepared by Using Er:YAG Laser with Different Pulse Modes. AB - OBJECTIVE: In vitro studies evaluated cementum surface morphology and microleakage of three different energy density parameters of Erbium: Yttrium Aluminum Garnet (Er:YAG) laser compared with diamond bur preparation on class V cavities with self-etch adhesive system and composite resin restoration. MATERIAL AND METHODS: Standard class V cavities were prepared at cervical area below the cementoenamel junction (CEJ) in 80 extracted premolars, by using a diamond bur on the buccal surface. All teeth were randomly allocated into four groups: Group 1, diamond bur; Group 2, Er:YAG 50 mJ/15 Hz, 3.77 J/cm(2); Group 3, Er:YAG 75 mJ/15 Hz, 5.65 J/cm(2); and Group 4, Er:YAG 100 mJ/15 Hz, 7.53 J/cm(2). Five cavities from each group were evaluated by scanning electron microscopy (SEM). The 15 remaining cavities from each group were restored with self-etch adhesive and nano hybrid composite. After thermocycling, all sample teeth were immersed in 0.2% methylene blue dye and sectioned buccolingually. Statistics were analyzed using the one way ANOVA and Mann-Whitney U tests with Bonferroni correction. RESULTS: The morphology showed micro-irregularities in the cementum surface of the laser group with the absence of a smear layer. The microstructure characteristics were increased surface roughness followed by increasing laser energy transmission. The Er:YAG laser groups were statistically significant, with less microleakage than the diamond bur group (p<0.05). There was statistically significant difference between the occlusal and gingival microleakage in all the groups (p<0.05). When the laser groups were compared, the lowest microleakage was achieved with energy density at 3.77 J/cm(2) on the occlusal and gingival cementum margin, which showed less microleakage than at energy densities of 5.65 and 7.53 J/cm(2) with Er:YAG laser. CONCLUSIONS: These observations indicate that the micro irregularities of the cementum surface could facilitate the formation of a hybridization zone with a self-etch adhesive system. Therefore, the microleakage of Er:YAG laser irradiation was significantly decreased compared with diamond bur cavities. PMID- 26270130 TI - Phytotherapeutic activity of curcumol: Isolation, GC-MS identification, and assessing potentials against acute and subchronic hyperglycemia, tactile allodynia, and hyperalgesia. AB - CONTEXT: Curcumol has recently attracted special attention due to its potential activities in many chronic disorders. Moreover, the traditional role of turmeric [Curcuma longa L. (Zingiberaceae)] in suppression of hyperglycemia is of great interest. OBJECTIVES: The present work explores the potential acute and subchronic antihyperglycemic, antinociceptive, and in vivo antioxidant effects of curcumol in alloxan-diabetic mice. MATERIALS AND METHODS: Bio-guided fractionation, column-chromatography, and GC-MS were utilized to identify the most active compound of turmeric (curcumol). Turmeric (25, 50, and 100 mg/kg), the curcumol rich fraction (CRF) (7 mg/kg), and curcumol (20, 30, and 40 mg/kg) were assessed for their acute (6 h) and subchronic (8 d) antihyperglycemic potentials and antinociceptive effects (8 weeks) were measured, using hot-plate and tail-flick latencies and von-Frey filaments method and in vivo antioxidant effects in alloxan-diabetic mice. RESULTS: The most-active turmeric fraction was found to be rich in curcumol (45.5%) using GC-MS analysis method. The results proved that the highest dose levels of turmeric extract and curcumol exerted remarkable hypoglycemic activity with 41.4 and 39.3% drop in the mice glucose levels after 6 h, respectively. Curcumol (40 mg/kg) was found to be 9.4% more potent than turmeric extract (100 mg/kg) in subchronic management of diabetes. Curcumol also showed a significant improvement of peripheral nerve function as observed from the latency and tactile tests. DISCUSSION: The antioxidant potential of curcumol may cause its ability to ameliorate diabetes and diabetes related complications. CONCLUSIONS: Curcumol, a natural metabolite with a good safety-profile, showed results comparable with tramadol in reversing diabetes induced tactile allodynia and hyperalgesia. PMID- 26270131 TI - Taxol prevents myocardial ischemia-reperfusion injury by inducing JNK-mediated HO 1 expression. AB - CONTEXT: Ischemia/hypoxia and reperfusion impair mitochondria and produce a large amount of reactive oxygen species (ROS), which lead to mitochondrial and brain damage. Furthermore, heme oxygenase-1 (HO-1) as a cytoprotective gene protects cells against ROS-induced cell death in ischemia-reperfusion injury. Induction of HO-1 is involved in cytoprotective effects of taxol. OBJECTIVE: We hypothesize that taxol protects cardiac myocytes possibly by preserving myocardial mitochondrial function and inducing HO-1 expression through the JNK pathway. MATERIALS AND METHODS: In this project, the perfused Langendorff hearts isolated from rats were randomly divided into five groups: control, ischemic, ischemic + taxol (0.1 MUM), ischemic + taxol (0.3 MUM), and ischemic + taxol (1 MUM). Briefly, following a 15 min equilibration period, the control group was subject to normoxic perfusion for 120 min; the ischemia group, normoxic reperfusion for 120 min after 30 min ischemia; the taxol groups, normoxic reperfusion for 120 min after 30-min ischemia with taxol (0.1, 0.3, or 1 MUM). The microtubule disruption score, ROS levels, and the activity of mitochondrial electron transport chain complexes I and III were examined by using immunohistochemical methods and free radical detection kits. Western blot assay was employed to study the underlying mechanisms. RESULTS: After Taxol treatment (0.1 uM), the ischemic microtubule disruption score was reduced to 9.8 +/- 1.9%. The study revealed that 0.1, 0.3, and 1 MUM taxol reduced the level of ROS by 33, 46 and 51%, respectively (p < 0.05). In additional, 0.3 and 1 MUM taxol dramatically increased the activity of mitochondrial electron transport chain complex I (99.11 +/- 2.59, 103.49 +/- 3.89) and mitochondrial electron transport chain complex III (877.82 +/- 12.08; 907.42 +/- 16.21; 914.73 +/- 19.39, *p < 0.05). Additionally, phosphorylation levels of JNK1 were significantly increased in the taxol group. Furthermore, the expression level of HO-1 increased with taxol treatments, which could be inhibited by the specific inhibitor of JNK, SP600125. DISCUSSION AND CONCLUSION: Taxol stabilized microtubules and effectively reduced ROS levels during ischemia. It also preserved the activity of mitochondrial complexes I and III. Interestingly, taxol induced the expression of HO-1 via the JNK pathway in cardiac myocytes. PMID- 26270133 TI - How to develop novel treatments for EGFR-mutant lung cancer. PMID- 26270132 TI - Oropharyngeal Candidiasis in Palliative Care Patients in Denmark. AB - BACKGROUND: Oropharyngeal candidiasis (OPC) is a significant cause of morbidity, especially among patients with advanced cancer. The incidence and significance of yeast carriage and OPC in the palliative care setting in Denmark is unknown. The best diagnostic strategy and treatment regimen has to be defined. OBJECTIVE: This study evaluated the clinical and microbiological incidence of yeast carriage/OPC and assessed available diagnostic procedures-culture and microscopy. The distribution of Candida species and fluconazole susceptibility was determined. METHODS: Terminal care patients admitted to Hospice Sjaelland (Denmark) March to June 2012 were included. Patients were evaluated for clinical OPC and a questionnaire including previous antifungal treatment was obtained. Paired samples from the buccal mucosa and the tongue were sent to microscopy and culture. In total, 105 microscopy slides and 105 cultures from 54 patients were included, yielding 71 Candida isolates. At admission, 22% were in fluconazole treatment and 56% had received an antifungal treatment within the last month. RESULTS: The yeast carriage rate was 83%, whereas 48% of the patients had clinical signs of OPC. Microscopy had low positive and negative predictive value (~50%). Candida albicans accounted for half of the isolates cultured. No C. albicans isolate displayed acquired fluconazole resistance; however, 3 out of 12 isolates of normally fluconazole-susceptible species were fluconazole resistant. These were all from patients recently treated with azoles. CONCLUSIONS: In total, 52% of culture-positive patients harbored at least one isolate with innately or acquired decreased fluconazole susceptibility. Therefore, susceptibility testing appears recommendable for patients with clinical signs of OPC. PMID- 26270134 TI - Bolus Estimation--Rethinking the Effect of Meal Fat Content. AB - BACKGROUND: Traditionally, insulin bolus calculations for managing postprandial glucose levels in individuals with type 1 diabetes rely solely on the carbohydrate content of a meal. However, recent studies have reported that other macronutrients in a meal can alter the insulin required for good postprandial control. Specifically, studies have shown that high-fat (HF) meals require more insulin than low-fat (LF) meals with identical carbohydrate content. Our objective was to assess the mechanisms underlying the higher insulin requirement observed in one of these studies. MATERIALS AND METHODS: We used a combination of previously validated metabolic models to fit data from a study comparing HF and LF dinners with identical carbohydrate content in seven subjects with type 1 diabetes. For each subject and dinner type, we estimated the model parameters representing the time of peak meal-glucose appearance (tau(m)), insulin sensitivity (S(I)), the net hepatic glucose balance, and the glucose effect at zero insulin in four time windows (dinner, early night, late night, and breakfast) and assessed the differences in model parameters via paired Wilcoxon signed-rank tests. RESULTS: During the HF meal, the tau(m) was significantly delayed (mean and standard error [SE]: 102 [14] min vs. 71 [4] min; P = 0.02), and S(I) was significantly lower (7.25 * 10(-4) [1.29 * 10(-4)] mL/MUU/min vs. 8.72 * 10(-4) [1.08 * 10(-4)] mL/MUU/min; P = 0.02). CONCLUSIONS: In addition to considering the putative delay in gastric emptying associated with HF meals, we suggest that clinicians reviewing patient records consider that the fat content of these meals may alter S(I). PMID- 26270135 TI - Analysis of the effects of topical renal hypothermia on lung tissue after kidney ischemia and reperfusion in rats. AB - PURPOSE: To evaluate whether topical renal hypothermia (TRH) at different levels of temperature has protective effects on lung tissue after renal I/R, through an analysis of organ histology and inflammatory markers in lung tissue. METHODS: Twenty-eight male Wistar rats were randomly allocated across four groups and subjected to renal ischemia at different levels of topical renal temperature: normothermia (no cooling, 37 degrees C), mild hypothermia (26 degrees C), moderate hypothermia (15 degrees C), and deep hypothermia (4 degrees C). To induce I/R, the vessels supplying the left kidney of each animal were clamped for 40 minutes, followed by reperfusion. After four hours, another procedure was performed to harvest the tissues of interest. TNF-alpha, IL-1beta and myeloperoxidase activity were measured in lung tissue. Histological analysis was performed in hematoxylin and eosin-stained lung specimens. RESULTS: Induction of renal I/R under deep topical hypothermia resulted in a significant decrease in lung concentrations of TNF-alpha compared with normothermic I/R (p<0.05). A trend toward significant correlation was found between lung IL-1beta concentration and intensity of hypothermia (Spearman r=-0.37; p=0.055). No difference was found in myeloperoxidase activity or histologic injury between groups. CONCLUSION: Topical renal hypothermia reduces activation of the inflammatory cascade in the lung parenchyma. However, tissue-protective effects were not observed. PMID- 26270136 TI - Effect of remote ischemic preconditioning in the expression of IL-6 and IL-10 in a rat model of liver ischemia-reperfusion injury. AB - PURPOSE: To study the effect of remote ischemic preconditioning (RIPC) in ischemia-reperfusion (I/R) liver injury and in the expression of IL-6 and IL-10 in a rat model. METHODS: Thirty-six male rats were divided in three groups: Sham; I/R injury, a 45 minutes lobar liver ischemia and reperfusion; and RIPC, six cycles of four minutes of ischemia and four minutes of reperfusion on the right hindlimb followed by a 45 minutes lobar liver ischemia and reperfusion. Tissue and blood samples were collected after 1h and 3h of reperfusion for histopathological study, plasma cytokines and alanine aminotransferase (ALT) measurement. RESULTS: The histopathological study demonstrated a significant reduction in liver necrosis in the RIPC group (p<0,001). The ALT levels were also significant lower in the RIPC group (p<0.01). The cytokines assessment showed that IL-6 levels were increased in the RIPC group after 1h of reperfusion, in comparison to the I/R group (p<0.05). Interleukin-10 levels in RIPC groups did not differ significantly from I/R group. CONCLUSIONS: Remote ischemic preconditioning is effective in decreasing liver necrosis in a rat model of ischemia-reperfusion. The IL-6 expression is up-regulated and peaked at 60 min of reperfusion. There was no difference in IL-10 expression between the groups. PMID- 26270137 TI - Effects of inferior splenic lobe pole fixation and gastrosplenic peritoneal membrane section on the vitality of the remanent of subtotal splenectomy in rats. AB - PURPOSE: To investigate the vitality of the spleen lower pole after subtotal splenectomy with suture to the stomach and after posterior peritoneal gastro splenic membrane section, using macro and microscopic evaluations. METHODS: Sixty Wistar rats were used in this study and were randomly distributed in the three groups: Group 1: (n=20), subtotal splenectomy with lower pole preservation, Group 2: (n=20) subtotal splenectomy with lower pole preservation and suture to the stomach, Group 3: subtotal splenectomy with lower pole preservation and posterior peritoneal gastrosplenic ligament section. The animals were sacrificed 45 days after the surgery and the spleen lower poles were removed for macroscopic and microscopic examination. RESULTS: All animals in this series survived. No macroscopic differences were encountered between the groups. Microscopic evaluation observed statistic difference concerning fibrosis between group 1 and 3 (p <= 0.05), but the analysis for necrosis and inflammation presented no differences. CONCLUSION: Vitality of the spleen lower pole after subtotal splenectomy is minimally modified when it is fixed to the stomach or when the posterior peritoneal gastrosplenic ligament is resected. PMID- 26270138 TI - Skin microcirculatory changes reflect early the circulatory deterioration in a fulminant sepsis model in the pig. AB - PURPOSE: In the pathophysiology of sepsis tissue perfusion dysfunction is a crucial driving force. Thus the early recognition is highly important. Concerning the early hours of bacteremia, and the systemic inflammatory response reaction leading to sepsis we aimed to investigate the micro- and macrocirculatory changes. METHODS: In 20 juvenile Hungahib pigs were anesthetized and the femoral artery and external jugular vein were prepared unilaterally and cannulated. For assisted ventilation tracheostomy was performed. In Sepsis group (n=11) live E. coli was intravenously administered (increasing concentration, 9.5x10?6 in 3h). In Control group (n=9) bacteria-free saline was administered at the same volume. Modified shock index (MSI), core and skin temperature, and skin microcirculation (laser Doppler) were measured before inducing bacteremia then hourly for 4h. RESULTS: In Control group parameters were stable, while six animals in the Sepsis group died before the 4th hour. Core and skin temperature did not show significant alterations. In Sepsis group microcirculation showed a large impairment already by the 1st hour, while in MSI only by the 3rd hour. CONCLUSION: During bacteremia and the early phase of sepsis microcirculatory impairment can be detected soon, even hours before the deterioration in hemodynamic parameters in this porcine model. PMID- 26270139 TI - Morphometric study of the corpus cavernosum after anabolic androgenic steroid administration in pubertal and adult rats. AB - PURPOSE: To evaluate the penile morphological modifications of pubertal and adult rats chronically treated with supra-physiological doses of anabolic androgenic steroids. METHODS: Forty-eight male Wistar rats were distributed into four groups: two control groups, 105- and 65-day-old (C105 and C65, respectively) injected with peanut oil (vehicle); and two treated groups, 105- and 65-day-old (T105 and T65, respectively) injected with nandrolone decanoate at a dose of 10 mg Kg-1 of body weight. The rats were injected once a week for eight weeks. The rats were then killed and their penises were processed for histomorphometric analyses. The mean of each parameter was statistically compared. RESULTS: A corpus cavernosum reduction of 12.5% and 10.9% was observed in the T105 and T65 groups, respectively, when compared with their respective control groups. The cavernosum smooth muscle surface density diminished by 5.6% and 12.9% in the T65 and T105 groups, respectively, when compared with their controls. In contrast, the sinusoidal space increased by 17% in the T105 group and decreased by 9.6% in the T65 group. CONCLUSION: The use of supra-physiological doses of AAS promotes structural changes in the rat penis, by altering the proportions of corpus cavernosum tissues, in both pubertal and adult treated animals. PMID- 26270140 TI - Myocardial contractility impairment with racemic bupivacaine, non-racemic bupivacaine and ropivacaine. A comparative study. AB - PURPOSE: To study racemic bupivacaine, non-racemic bupivacaine and ropivacaine on myocardial contractility. METHODS: Isolated Wistar papillary muscles were submitted to 50 and 100 mM racemic bupivacaine (B50 and B100), non-racemic bupivacaine (NR50 and NR100) and ropivacaine (R50 and R100) intoxication. Isometric contraction data were obtained in basal condition (0.2 Hz), after increasing the frequency of stimulation to 1.0 Hz and after 5, 10 and 15 min of local anesthetic intoxication. Data were analyzed as relative changes of variation. RESULTS: Developed tension was higher with R100 than B100 at D1 (4.3 +/- 41.1 vs -57.9 +/- 48.1). Resting tension was altered with B50 (-10.6 +/- 23.8 vs -4.7 +/- 5.0) and R50 (-14.0 +/- 20.5 vs -0.5 +/- 7.1) between D1 and D3. Maximum rate of tension development was lower with B100 (-56.6 +/- 38.0) than R50 (-6.3 +/- 37.9) and R100 (-1.9 +/- 37.2) in D1. B50, B100 and NR100 modified the maximum rate of tension decline from D1 through D2. Time to peak tension was changed with NR50 between D1 and D2. CONCLUSIONS: Racemic bupivacaine depressed myocardial contractile force more than non-racemic bupivacaine and ropivacaine. Non-racemic and racemic bupivacaine caused myocardial relaxation impairment more than ropivacaine. PMID- 26270141 TI - Antimicrobial activity of Melaleuca sp. oil against clinical isolates of antibiotics resistant Staphylococcus aureus. AB - PURPOSE: To extract the Melaleuca sp. oil and to assess its in vitro inhibitory effect against Staphylococcus aureus isolates obtained from lower limb wounds and resistant to several antibiotics. METHODS: A total of 14 test-tubes containing Mueller-Hinton broth were used to determine the Minimum Inhibitory Concentration (MIC). The following concentrations of the Melaleuca sp. oil were added to the first 11 tubes: 8; 4; 2; 1; 0.5; 0.2; 0.1; 0.05; 0.025; 0.0125 and 0.00625%. The 12th and 13th tubes, with and without oil, were used as the positive and negative controls, respectively. The experimental study was carried out in triplicate at 37oC for 18 hours. The Minimum Bactericidal Concentration (MBC), able of killing all the microorganisms, was also determined. Two S. aureus isolates were obtained from lower limb wounds of female patients and the identification of the microorganisms (Staphylococcus aureus) and the test for susceptibility to the antimicrobial agents were carried out by automation using the apparatus MicroScan(r). After identification, the isolates were preserved in liquid Trypticase Soy medium, and inoculated for determination of the MIC and MBC. RESULTS: The MIC was 0.2% and the MBC was 0.4%. CONCLUSION: The Melaleuca sp. oil showed antimicrobial properties in vitro against strains isolated from lower limb wounds which were resistant to multiple antibiotics. PMID- 26270142 TI - Analysis of effect isoxsuprine hydrochloride and nicotine in the Transverse Rectus Abdominis Myocutaneous flap (TRAM) in rats. AB - PURPOSE: To evaluate the effects of isoxsuprine and nicotine on TRAM. METHODS: Forty eight 48 Wistar rats distributed into four Groups (n=12). All rats received medication managed daily for 20 days: saline solution (SA), nicotine solution (NI), isoxsuprine solution (IS) and nicotine solution (NI) + isoxsuprine solution (IS). On day 21st the rats were submitted to the caudally based, right unipedicled TRAM flap and after 48 hours, made the macroscopic evaluation of the surface of the flap, photographic documentation and collection of material for histology. Data from macroscopic evaluation were analyzed by ANOVA and microscopic evaluation by Kruskal-Wallis test, with significance level of 5%. RESULTS: In the macroscopic evaluation of isoxsuprine Group retail presented absolute numbers: final area (p=0.001*) and viable area (p=0.006*) with the highest values; necrosis (p=0.001*) had the lowest value. Microscopic examination revealed no significant findings in the study of TRAM under the action of isoxsuprine and nicotine to the percentage of necrosis in the left and right cranial and caudal regions. CONCLUSIONS: There was significant improvement in viability of TRAM using the isoxsuprine solution alone. No influence using nicotine alone and in association with isoxsuprine. PMID- 26270143 TI - Rapid on-site cytopathological examination (ROSE) performed by endosonagraphers and its improvement in the diagnosis of pancreatic solid lesions. AB - PURPOSE: To evaluate the diagnosis improvement of EUS-FNA when using ROSE performed by the endosonographer. METHODS: A retrospective study was conducted. A total of 48 pancreatic solid masses EUS-FNA were divided into two groups according to the availability of on-site cytology (ROSE) - the first 24 patients (group A-without ROSE) and the latter 24 cases (group B-with ROSE). Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, complications and inadequacy rate of EUS-FNA were determined and compared. RESULTS: Among the 48 EUS-FNA, the overall performance was: sensitivity 82%; specificity 100%; positive predictive value (PPV) 100%; negative predictive value (NPV) 70% and accuracy 87%. The sensitivity of the Group A was 71%, versus 94% in group B (p=0.61). Moreover, the negative predictive value was 58% versus 87% (p=0.72). The accuracy rate increased from 79% to 96% (p=0.67) in the ROSE group. The number of punctures was similar between the groups. No major complications were reported. CONCLUSION: Rapid on-site cytopathological examination, even when performed by the endosonographer, may improve the diagnostic performance in the diagnosis of solid pancreatic lesions, regardless of the slight increase in the number of punctures. PMID- 26270145 TI - Tuneable anisotropy and magnetism in Sn2Co3S2-xSex - probed by (119)Sn Mobetabauer spectroscopy and DFT studies. AB - The half metal (HFM) Sn2Co3S2 shows a fascinating S = 1/2 magnetism. Anisotropic coupling of spins in and between Co Kagome layers by Sn sites is now studied from the substitution effects of S by Se by systematic and local experimental and first principles data. Trends in crystal structure changes (c/a ratio) as retrieved from XRD data on the solid solution Sn2Co3S2-xSex are complemented by DFT modelling on Sn2Co3SeS and hitherto unknown Sn2Co3Se2. The relationship of crystal structure effects with changes in Curie temperatures and magnetic hysteresis is shown from susceptibility measurements. An insight into the role of the Sn sites in magnetism and bonding is gained from (119)Sn Mossbauer spectroscopic measurements. Isomer shifts, quadrupole splitting, and magnetic hyperfine fields are interpreted by DFT calculations on chemical bonding, electric field gradients (EFG), Fermi contact, and spin polarization. PMID- 26270144 TI - Photographs for anthropometric measurements of the breast region. Are there limitations? AB - PURPOSE: To determine the limitations of the photographs used to obtain the anthropometric measurements of the breast region. METHODS: Five women, between the ages of 18 to 60 years, were evaluated. Photographs of the frontal and left and right profile views of their breasts were taken. Based on the current literature, the most commonly used anthropometric and anatomic landmarks for breast measurement were marked in their different positions. The different points were used to evaluate if the direct anthropometry was possible in a standardized way and determine how the points and the positions can to be used in any breast measurements. RESULTS: There were some limitations to the use of defining points of the breast fold, as well as of its lower portion and lateral extension positions in both profiles. CONCLUSION: The defining points of the breast fold and the profile photographs have some limitations and we suggested how the points and positions can be used for breasts measurements. PMID- 26270146 TI - Label-free detection of missense mutations and methylation differences in the p53 gene using optically diffracting hydrogels. AB - We have developed a novel approach for DNA detection as well as genetic screening of mutations by uniquely combining DNA-responsive and optically diffracting materials. This approach entails the polymerization of a photonic crystal within a hydrogel network that alters the diffraction of light in response to a target DNA strand. The utility of this approach, which permits label-free sensing, was demonstrated via the detection of a target sequence from the DNA binding domain of the major tumor suppressor protein p53. Using a complementary capture probe strand, we were able to detect down to picomole concentrations of the target p53 sequence. Moreover, we demonstrated that this approach could readily detect a single base pair mutation in the target strand, which corresponds to the hotspot cancer mutation R175H in p53. The sensitivity of detection was increased by lowering the rate of annealing of the target strand and adjusting the solution ionic strength during optical characterization. Changes in ionic strength during characterization impact the melting temperature of the bound target DNA and the Donnan potential between the hydrogel and solution, which influence detection. We further showed that this approach is sensitive to epigenetic changes via the detection of a fully methylated form of the target p53 sequence. Ultimately, this approach represents a new paradigm for DNA detection and specifically genetic screening of p53 as well as other disease markers and nucleotide modifications that alter the properties of DNA (e.g., epigenetic alterations and adducts with chemical carcinogens). PMID- 26270147 TI - The Effect of Systemic Carnitine Administration on Colon Anastomosis Healing in an Experimental Sepsis Model. AB - AIM: This study aimed to investigate the effects of L-carnitine, with its known antioxidant properties and positive effects on wound healing, on the healing of colon anastomosis in a cecal ligation and puncture sepsis model in rats. MATERIALS AND METHODS: A total of 40 Sprague-Dawley rats were used. The rats were randomly divided into four groups of 10 (n = 10). Groups 1 and 2 had laparotomy and colon anastomosis performed. Groups 3 and 4 had cecal ligation and puncture (CLP) and colon anastomosis performed. Rats in Groups 1 and 3 were given 15 mL/kg intraperitoneal 0.9% isotonic NaCl, while the rats in Groups 2 and 4 were given 100 mg/kg intraperitoneal L-carnitine. On the postoperative fifth day, the rats were sacrificed and the burst pressure of anastomosis, histopathological effects, and tissue hydroxyproline levels were investigated. RESULTS: In Groups 2 and 4, the anastomosis burst pressure and histopathological results in both noninfected abdomen and presence of peritonitis were statistically high compared to the control group (p < 0.05). Though the hydroxyproline levels were also high, there was no statistically significant difference for this parameter (p > 0.05). CONCLUSIONS: The findings obtained from the experimental sepsis model showed that healing of anastomosis in both the presence of peritonitis and noninfected abdomen was positively affected by the systemic administration of L-carnitine and this may contribute to the safety of anastomosis. PMID- 26270148 TI - A Scholarship of Practice Revisited: Creating Community-Engaged Occupational Therapy Practitioners, Educators, and Scholars. AB - Trends in policy, practice, and research point to the need for a community engaged Scholarship of Practice (SOP) model that can be used to inform the development of occupational therapy practitioners, educators, and researchers. This article describes a community-engaged SOP model, the evidence justifying the need for such a model, and strategies to effectively create community-engaged practitioners, educators and career scientists within occupational therapy. We highlight several examples of community-based participatory research to further inform this model, and in turn, translate this knowledge back to communities for action and systems change that can affect the lives of people with disabilities and the communities in which they seek to live and participate long term. PMID- 26270149 TI - Bufotenine - A Hallucinogen in Ancient Snuff Powders of South America and a Drug of Abuse on the Streets of New York City. AB - Bufotenine, an isomer of psilocin, is a controlled Schedule I hallucinogenic substance under the New York state and Federal laws. Bufotenine was identified in 42 case samples received at the New York City Police Laboratory since May 1992. The samples were hard, resinous, dark reddish-brown material, sold on the streets as "hashish". A few other cases were also seized in Orlando and Tampa, FL. Natural sources of bufotenine are: (a) plant material, mostly seeds of the genus Anadenanthera (formerly Piptadenia); (b) plant organs of other genera; (c) toads (Bufo marinus, B. vulgaris, B. viridian, and B. avarice); and (d) mushrooms (Amanita amp, A. Citrina, A. Porphyria, and A. tomentella). The genus Anadenanthera is native to South America and West Indies. Historically, material made from seeds of genus Anadenanthera was, and in isolated areas is still, used by the native Indians of South America and West Indies. Native Indians make intoxicating snuffs from the seeds of Anadenanthera. Recently, bufotenine was identified in 1,200-year-old archaeological samples of an Anadenanthera material found in an excavated tomb in Northern Chile. Historical and published literature on the pharmacology, toxicology, and biological effects of bufotenine and bufotenine-containing material are reviewed. The case material was probably derived from the seeds of genus Andenanthera. There were no prior reported cases of this material being used outside the native Indian areas of South America and West Indies. Indications are that in New York City this material is smoked in combination with marijuana. Bufotenine in case material can be identified by color test, thin-layer chromatography, and gas chromatography/mass spectrometry (GC/MS). Though the mass spectra of bufotenine and psilocin (parent compounds and mono-acetyl and di-acetyl derivatives) are very similar, their GC retention times are different. Case samples also gave multiple GC peaks, probably due to the added ingredients during the preparation of this material. PMID- 26270150 TI - Comparison of Common Immunoassay Kits for Effective Application in Workplace Drug Urinalysis. AB - Workplace drug urinalysis protocols include an initial immunoassay followed by a confirmation gas chromatography/mass spectrometry (GC/MS) test of immunoassay positive samples. (Drug categories that are commonly tested include: amphetamines, barbiturates, benzodiazepines, cannabis, cocaine, lysergic acid diethyl amide, methadone, methaqualone, opiates, phencyclidine, and propoxyphene. Not all drug categories are tested by all workplace drug urinalysis programs.) Only those samples that are tested positive by both the initial and the confirmatory procedures can be reported as positive. Thus, when adopting an immunoassay, one must have knowledge of the assay's cross-reacting characteristics and the assay's apparent analyze concentration that corresponds to a specific analyze concentration determined by the GC/MS procedure. The underlying principles of the commonly used radioimmunoassay, enzyme immunoassay, fluorescence polarization immunoassay, and particle immunoassay are outlined. Cross-reacting characteristics of these immunoassays as reported by the manufacturers and independent laboratories are tabulated. This information shown that commercial immunoassay kits for drug categories that are included in workplace drug urinalysis programs are generally more specific than those kits that are for clinical use only. Furthermore, recently manufactured immunoassay kits targeted for use in workplace drug urinalysis programs are more specific than those manufactured earlier. Reported effects of adulterants, such as salt, cleaning agents, etc., on commonly used immunoassays are summarized. Without more comprehensive and systematic studies, it is difficult to make general statements concerning the superiority of one methodology over the others. It is clear, however, that cannabinoid assesses are most susceptible to the influence of adulterants. Reported immunoassay-GC/MS correlation data are reviewed. Significant correlations exist in all cases. The immunoassay apparent analyze concentration corresponding to a specific GC/MS analyze concentration may be approximately based on the resulting regression equations. Since the corresponding immunoassay apparent analyze concentrations vary with the specificities of the reagent used, the immunoassay reagent manufacturers should carefully study specificity characteristics of each manufacturing batch and provide these correlation data for users' evaluation and adaptation. PMID- 26270151 TI - Fibers and Forensic Science - New Ideas, Developments, and Techniques. AB - The techniques used for present day recovery, examination, and comparison of textile fibers in forensic science are outlined. The author has not concentrated on the already well established theories of transfer and persistence and the basic methodology, as these topics have been repeatedly reported in detail relatively recently. Instead he has given his attention primarily to developments that have occurred within the last five years, to new areas of research, and to new instrumental methods that many become integrated into the standard operating procedures of the future. The final sections are devoted to looking at some new types of fibers and at the changing views on how best to express the evidential value of fibers evidence. PMID- 26270152 TI - Assisted Reproductive Technology Surveillance - United States, 2012. AB - PROBLEM/CONDITION: Since the first U.S. infant conceived with Assisted Reproductive Technology (ART) was born in 1981, both the use of advanced technologies to overcome infertility and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Because more than one embryo might be transferred during a procedure, women who undergo ART procedures, compared with those who conceive naturally, are more likely to deliver multiple birth infants. Multiple births pose substantial risks to both mothers and infants, including obstetric complications, preterm delivery, and low birthweight infants. This report provides state-specific information for the United States (including Puerto Rico) on ART procedures performed in 2012 and compares infant outcomes that occurred in 2012 (resulting from ART procedures performed in 2011 and 2012) with outcomes for all infants born in the United States in 2012. PERIOD COVERED: 2012. DESCRIPTION OF SYSTEM: In 1996, CDC began collecting data on ART procedures performed in fertility clinics in the United States, as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA) (Public Law 102-493). Data are collected through the National ART Surveillance System, a web-based data collecting system developed by CDC. This report includes data from 52 reporting areas (the 50 states, the District of Columbia [DC], and Puerto Rico). RESULTS: In 2012, a total of 157,635 ART procedures performed in 456 U.S. fertility clinics were reported to CDC. These procedures resulted in 51,261 live-birth deliveries and 65,151 infants. The largest numbers of ART procedures were performed among residents of six states: California (20,241), New York (19,618), Illinois (10,449), Texas (10,281), Massachusetts (9,754), and New Jersey (8,590). These six states also had the highest number of live-birth deliveries as a result of ART procedures, and together they accounted for 50.1% of all ART procedures performed, 48.3% of all infants born from ART, and 48.3% of all ART multiple live-birth deliveries. Nationally, the total number of ART procedures performed per 1 million women of reproductive age (15-44 years), which is a proxy indicator of ART use, was 2,483. This indicator of ART use exceeded the national ratio in 13 reporting areas (California, Connecticut, Delaware, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Virginia, and DC) and was more than twice the national ratio in three reporting areas (Massachusetts, New Jersey, and DC). Nationally, among ART cycles with patients using fresh embryos from their own eggs, in which at least one embryo was transferred, the average number of embryos transferred increased with the increasing age of the woman (1.9 among women aged <35 years, 2.2 among women aged 35-40 years, and 2.7 among women aged >40 years). The percentage of elective single-embryo transfer (eSET) procedures varied substantially between reporting areas for all ages. Among women aged <35 years, who are typically considered to be good candidates for eSET procedures, the national eSET rate was 15.3% (range: 2.1% in Oklahoma to 60.4% in Delaware). Overall, ART contributed to 1.5% of all infants born in the United States (range: 0.2% in Puerto Rico to 4.7% in Massachusetts) with the highest rates (>=3.0% of all infants born) observed in four reporting areas (Connecticut, Massachusetts, New Jersey, and DC). Infants conceived with ART comprised 19.6% of all multiple-birth infants (range: 5.5% in Maine to 39.3% in Massachusetts), 19.2% of all twin infants (range: 4.4% in Puerto Rico to 39.1% in Massachusetts), and 29.6% of all triplet or higher order infants (range: 0 in West Virginia to 69.7% in Idaho). Among infants conceived with ART, 43.6% were born in multiple birth deliveries (range: 18.7% in Delaware to 56.0% in Idaho), compared with only 3.4% among all infants born in the general population (range: 2.1% in Puerto Rico to 4.5% in New Jersey). Approximately 41% of ART-conceived infants were twin infants, and 2% were triplet and higher order infants. Nationally, infants conceived with ART comprised 5.7% of all low birthweight (<2,500 grams) infants (range: 0.8% in Puerto Rico to 15.3% in Massachusetts) and 5.8% of all very low birthweight (<1,500 grams) infants (range: 0 in West Virginia to 15.1% in New Jersey). Overall, among ART-conceived infants, 30.2% were low birthweight (range: 18.8% in DC to 45.1% in New Mexico), compared with 8.0% among all infants (range: 5.6% in Alaska to 11.6% in Mississippi and Puerto Rico); 5.5% of ART infants were very low birthweight (range: 0 in West Virginia to 12.9% in Puerto Rico), compared with 1.4% among all infants (range: 0.9% in Alaska and Idaho to 2.1% in Mississippi). ART-conceived infants comprised 4.6% of all preterm (<37 weeks) infants (range: 0.7% in Puerto Rico to 13.4% in Massachusetts) and 5.2% of all very preterm (<32 weeks) infants (range: 1.0% in Puerto Rico to 14.9% in Vermont). Overall, among infants conceived with ART, 34.9% were born preterm (range: 20.8% in Delaware and DC to 49.4% in Puerto Rico), compared with 11.6% among all infants born in the general population (range: 8.7% in Vermont to 17.1% in Mississippi); 6.5% of ART infants were born very preterm (range: 3.3% in Nevada to 14.8% in South Dakota), compared with 1.9% among all infants born in the general population (range: 1.1% in Vermont to 2.9% in Mississippi). The percentage of infants conceived with ART who were low birthweight varied from 9.3% (range: 4.1% in South Carolina to 20.9% in Puerto Rico) among singletons, to 55.2% (range: 41.5% in New Hampshire to 83.3% in South Dakota) among twins, and 95.3% (range: 85.2% in Oklahoma to 100% in several reporting areas) among triplets or higher-order multiples; comparable percentages for all infants were 6.3% (range: 4.5% in Alaska to 10.3% in Puerto Rico), 55.4% (range: 46.0% in Alaska to 69.0% in Puerto Rico), and 91.6% (range: 80.6% in Missouri to 100% in several reporting areas), respectively. The percentage of ART infants who were preterm varied from 13.2% (range: 9.4% in West Virginia to 25.4% in North Dakota) among singletons, to 61.0% (range: 47.8% in DC to 80.0% in Maine and West Virginia) among twins, and 97.7% (range: 92.7% in Massachusetts to 100% in several reporting areas) among triplets or higher-order multiples; comparable percentages for all infants were 9.9% (range: 7.3% in Vermont to 15.8% in Puerto Rico), 56.8% (range: 47.2% in Connecticut to 67.2% in Puerto Rico), and 92.6% (range: 36.4% in Oregon to 96.8% in Ohio), respectively. INTERPRETATION: The percentage of infants conceived with ART varied considerably by reporting area. In most reporting areas, multiples from ART comprised a substantial proportion of all twin, triplet, and higher-order infants born, and the rates of low birthweight and preterm infants were disproportionately higher among ART infants than in the birth population overall. Among women aged <35 years, eSET procedures warrant consideration because these patients might have extra embryos available for cryopreservation, which is a good predictor of embryo quality, and might have a more favorable prognosis for a live birth than older patients. However, on average, two embryos were transferred per cycle in ART procedures among women aged <35 years, influencing the overall multiple-birth rates in the United States. Compared with ART singletons, ART twins were approximately four and a half times more likely to be born preterm, and approximately six times more likely to be born with low birthweight. Singleton infants conceived with ART had slightly higher rates of preterm delivery and low birthweight than all singleton infants born in the United States. ART use per population unit was geographically varied, with 12 states showing ART use above the national rate. Of the four states (Illinois, Massachusetts, New Jersey, and Rhode Island) with comprehensive statewide-mandated health insurance coverage for ART procedures (e.g., coverage for at least four cycles of in vitro fertilization), two states (Massachusetts and New Jersey) had rates of ART use exceeding twice the national level. This type of mandated insurance has been associated with greater use of ART and might account for some of the difference in per capita ART use observed among states. PUBLIC HEALTH ACTIONS: Reducing the number of embryos transferred per ART procedure and increasing use of eSET, when clinically appropriate (typically age <35 years), might reduce multiple births and related adverse consequences of ART. Improved patient education and counseling on the maternal and infant health risks of having twins are needed given that twins account for the majority of ART conceived multiple births. Although ART contributes to increasing rates of multiple births, it does not explain all of the increases. Other explanations for multiple births not investigated in this report might include age-related factors and the role of non-ART fertility treatments, and warrant further study. PMID- 26270154 TI - Three-Dimensional Confocal Microscopy Indentation Method for Hydrogel Elasticity Measurement. AB - The stiffness of the extracellular matrix (ECM) plays an important role in controlling cell functions. As an alternative to the ECM, hydrogels of tunable elasticity are widely used for in vitro cell mechanobiology studies. Therefore, characterizing the Young's modulus of the hydrogel substrate is crucial. In this paper, we propose a confocal microscopy indentation method for measuring the elasticity of polyacrylamide gel as a model hydrogel. Our new indentation method is based on three-dimensional imaging of the indented gel using confocal microscopy and automated image processing to measure indentation depth from the three-dimensional image stack. We tested and validated our method by indenting polyacrylamide gels of different rigidities with various sphere indentors and by comparing it with the rheometric method. Our measurements show consistent results regardless of the type of the indentors and agree with rheometric measurements. Therefore, the proposed confocal microscopy indentation method can accurately measure the stiffness of hydrogels. PMID- 26270155 TI - Anxiety, depression, and oral health among US pregnant women: 2010 Behavioral Risk Factor Surveillance System. AB - OBJECTIVES: Maternal periodontal disease is associated with adverse perinatal outcomes. Anxiety and depression adversely impact oral health in nonpregnant women; however, this association has not been evaluated during pregnancy, a time characterized by higher rates of anxiety and depression. Therefore, we examined the association between these factors and oral disease and oral healthcare utilization among 402 pregnant respondents to the 2010 Behavioral Risk Factor Surveillance System. METHODS: Self-reported lifetime diagnoses of anxiety, depression, and current depression were assessed. Oral health outcomes included self-reported tooth loss and dental visits in the past year. RESULTS: One-fifth (21.2 percent) of respondents reported a tooth loss and 32.5 percent reported nonuse of oral health services. The prevalence of lifetime diagnosed anxiety and depression was 13.6 percent and 11.3 percent, respectively, whereas 10.6 percent reported current depression. After adjusting for risk factors, pregnant women with diagnosed anxiety had increased odds of one or more tooth loss [odds ratio (OR) = 3.30; 95 percent confidence interval (CI): 1.01-10.77] compared with those without the disorder. Similarly, after adjusting for socioeconomic factors, women with anxiety had increased odds of nonuse of oral health services (OR = 2.67; 95 percent CI: 1.03-6.90); however, this was no longer significant after adjusting for health behaviors and body mass index. We observed no significant association with depression. CONCLUSIONS: In this population-based sample, we found a two- to threefold increased odds of tooth loss and nonuse of oral health services among pregnant women with a lifetime diagnosis of anxiety. To our knowledge, this is the first study to examine these associations among pregnant women. PMID- 26270156 TI - The difference between blood-associated and water-associated herbs of Danggui Shaoyao San in theory of TCM, based on serum pharmacochemistry. AB - Danggui-Shaoyao San (DSS) is a famous Chinese formula for activating blood circulation and promoting urination. This study was to investigate the difference of material basis between a blood-associated herbs group and a water-associated herbs group. According to the theory of traditional Chinese medicine, the formula can be divided into a blood-associated herbs group (Angelica sinensis, Paeonia lactiflora and Ligusticum chuanxiong) and a water-associated herbs group (Atractylodes macrocephala, Alisma orientale and Poria cocos). The HPLC fingerprint of the formula was established for quality control. Serum samples from rats, orally administrated DSS, and the decomposed recipes of DSS, were analyzed by HPLC-DAD and the transitional blood components of DSS were identified. Twenty-one common peaks were identified in the fingerprint of DSS. Contents of paeoniflorin, albiflorin, ferulic acid and alisol B 23-acetate in co decoction were significantly higher than those in individual decoction. Eleven peaks belonged to the blood-associated herbs group (four metabolites and seven prototype components; paeoniflorin and ferulic acid appeared in prototype components), whereas six peaks belonged to the water-associated herbs group (three metabolites and three prototype components). It was concluded that the serum pharmacochemistry is a meaningful approach for clarifying the difference between blood-associated and water-associated herbs in chemical composition. PMID- 26270157 TI - Reactivity of a Zn(Cys)2(His)2 Zinc Finger with Singlet Oxygen: Oxidation Directed toward Cysteines but not Histidines. AB - Singlet oxygen ((1)O2) is an important reactive oxygen species in biology that has deleterious effects. Proteins constitute the main target of (1)O2 in cells. Several organisms are able to mount a transcriptional defense against (1)O2. ChrR and MBS are two proteins with Zn(Cys)2(His)2 zinc finger sites that are involved in the regulation of the defense against (1)O2. In this article, we investigate the reactivity of Zn?CPF, a Zn(Cys)2(His)2 classical betabetaalpha zinc finger, with (1)O2. We show that Zn?CPF interacts with (1)O2 mainly by physical quenching using a combination of (1)O2 luminescence quenching and kinetic competition experiments. The chemical reaction, which accounts for 5% of the interaction, leads to oxidation of cysteines but not histidines. Primary photooxidation products, identified by HPLC and mass spectrometry, are sulfinate (75+/-5%) and disulfides (25+/-5%). The peptides that have a single cysteine thiolate oxidized into a sulfinate are still able to bind one equivalent Zn(2+) but with a dramatic reduction of the binding constant compared to Zn?CPF despite the preservation of the betabetaalpha fold, as shown by NMR and CD titrations. Finally, Zn?CPF is compared to Zn?LTC, a treble clef Zn(Cys)4 zinc finger, to gain further insight into the behavior of zinc fingers toward (1)O2. PMID- 26270158 TI - Two-Dimensional, Porous Nickel-Cobalt Sulfide for High-Performance Asymmetric Supercapacitors. AB - High specific surface area, high electrical conductivity, and abundant channels have been recognized to favor pseudocapacitors, but their realization at the same time is still a great challenge. Here, we report on nickel-cobalt sulfide nanosheets (NSs) with both ultrathin thickness and nanoscale pores for supercapacitors. The porous Ni-Co sulfide NSs were facilely synthesized through micelle-confined growth and subsequent sulfuration. The NSs are as thin as several nanometers and have a large number of pores with a mean size of ~7 nm, resulting in ultrahigh atom ratio at surface with unique chemical and electronic structure. Therefore, fast diffusion of ions, facile transportation of electrons and high activity make great synergistic contributions to the surface-dependent reversible redox reactions. In the resulted supercapacitors, a specific capacitance of 1304 F g(-1) is achieved at a current density of 2 A g(-1) with excellent rate capability that 85.6% of the original capacitance is remained at 20 A g(-1). The effects of crystallinity and self-doping are optimized so that 93.5% of the original capacitance is obtained after 6000 cycles at a high current density of 8 A g(-1). Finally, asymmetric supercapacitors with a high energy density of 41.4 Wh/kg are achieved at a power density of 414 W/kg. PMID- 26270159 TI - Correction to "Toward an Enhancement of the Photoactivity of Multiphotochromic Dimers Using Plasmon Resonance: A Theoretical Study". PMID- 26270160 TI - Identification of Core Segment of Amyloidal Peptide Mediated by Chaperone Molecules by using Scanning Tunneling Microscopy. AB - We illustrate in this work that pristine assemblies of amyloidal peptides can be obtained by perturbations of reduced scanning bias, and show a broad distribution in peptide length. In contrast, the chaperone-mediated peptide co-assembly presents ordered lamellar structures with a homogeneous distribution in length, which could be attributed to the core segment of the peptide. The efforts are beneficial for gaining insight into the aggregation propensity of peptides and inter-peptide interactions. PMID- 26270169 TI - Using SOAPaligner for Short Reads Alignment. AB - This unit shows how to use the SOAPaligner package to align short reads to reference. The use of the two most common versions of SOAPaligner, SOAP2 and SOAP3-dp, will be described in detail. The unit also includes a protocol for SNP calling from SOAP2 alignment with SOAPsnp. PMID- 26270170 TI - An Overview of RNA Sequence Analyses: Structure Prediction, ncRNA Gene Identification, and RNAi Design. AB - This unit briefly describes the two fundamentally different methods for predicting RNA structures. The first is to find that structure with the minimum free energy of folding, as predicted by various thermodynamic parameters related to base-pair stacking, loop lengths, and other features. If one has only a single sequence, this thermodynamic approach is the best available method. The second fundamental approach to RNA structure prediction is to use multiple, homologous sequences for which one can infer a common structure, and then try and predict a structure common to all of the sequences. Such an approach is referred to as a comparative method or phylogenetic method of RNA structure prediction. PMID- 26270168 TI - The prediction of postoperative stroke or death in patients with preoperative atrial fibrillation undergoing non-cardiac surgery: a VISION sub-study. AB - BACKGROUND: The optimal means of pre-operative risk stratification in patients with atrial fibrillation (AF) is uncertain. OBJECTIVE: To examine the accuracy of AF thromboembolic risk models (the CHADS2, CHA2DS2-VASc, and R2CHADS2 scores) for predicting 30-day stroke and/or all-cause mortality after non-cardiac surgery in patients with preoperative AF, and to compare these risk scores with the Revised Cardiac Risk Index (RCRI). PATIENTS/METHODS: A multicentre (8 countries, 2007 2011) prospective cohort study of patients >= 45 years of age undergoing inpatient non-cardiac surgery, who were followed until 30 days after surgery. We calculated c-statistics for each risk prediction model and net reclassification improvements (NRIs) compared with the RCRI. RESULTS: The 961 patients with preoperative AF were at higher risk of any cardiovascular event in the 30 days postoperatively compared with the 13 001 patients without AF: 26.6% vs. 9.0%; adjusted odds ratio, 1.58; 95% confidence interval [CI], 1.33-1.88. All thromboembolic risk scores predicted postoperative death just as well as the RCRI (with c-indices between 0.67 and 0.72). Compared with the RCRI (which had a c index of 0.64 for 30-day stroke/death), the CHADS2 (c-index, 0.67; NRI, 0.31; 95% CI, 0.02-0.61) significantly improved postoperative stroke/mortality risk prediction, largely due to improved discrimination of patients who did not subsequently have an event. CONCLUSIONS: In AF patients, the three thromboembolic risk scores performed similarly to the RCRI in predicting death within 30 days and the CHADS2 score was the best predictor of postoperative stroke/death regardless of type of surgery. PMID- 26270171 TI - LipidXplorer: Software for Quantitative Shotgun Lipidomics Compatible with Multiple Mass Spectrometry Platforms. AB - LipidXplorer is an open-source software kit that supports the identification and quantification of molecular species of any lipid class detected by shotgun experiments performed on any mass spectrometry platform. LipidXplorer does not rely on a database of reference spectra: instead, lipid identification routines are user defined in the declarative molecular fragmentation query language (MFQL). The software supports batch processing of multiple shotgun acquisitions by high-resolution mass mapping, precursor and neutral-loss scanning, and data dependent MS/MS lending itself to a variety of lipidomics applications in cell biology and molecular medicine. PMID- 26270172 TI - Cloud Computing with iPlant Atmosphere. AB - Cloud Computing refers to distributed computing platforms that use virtualization software to provide easy access to physical computing infrastructure and data storage, typically administered through a Web interface. Cloud-based computing provides access to powerful servers, with specific software and virtual hardware configurations, while eliminating the initial capital cost of expensive computers and reducing the ongoing operating costs of system administration, maintenance contracts, power consumption, and cooling. This eliminates a significant barrier to entry into bioinformatics and high-performance computing for many researchers. This is especially true of free or modestly priced cloud computing services. The iPlant Collaborative offers a free cloud computing service, Atmosphere, which allows users to easily create and use instances on virtual servers preconfigured for their analytical needs. Atmosphere is a self-service, on-demand platform for scientific computing. This unit demonstrates how to set up, access and use cloud computing in Atmosphere. PMID- 26270173 TI - Common File Formats. AB - An overview of the many file formats commonly used in bioinformatics and genome sequence analysis is presented, including various data file formats, alignment file formats, and annotation file formats. Example workflows illustrate how some of the different file types are typically used. PMID- 26270174 TI - Improved Protocols for Illumina Sequencing. AB - In this unit, we describe a set of improvements that have been made to the standard Illumina protocols to make the sequencing process more reliable in a high-throughput environment, reduce amplification bias, narrow the distribution of insert sizes, and reliably obtain high yields of data. PMID- 26270175 TI - Modeling an Inflammation-Related Depressive Phenotype in Mice Using Bacille Calmette-Guerin. AB - The relationship between inflammation and neuropsychiatric symptoms is of interest to the scientific community for several reasons. A substantial subset of patients suffering from major depressive disorder also exhibit evidence of chronic inflammation including elevated levels of circulating pro-inflammatory cytokines. Immune-mediated inflammatory diseases and immunotherapy can result in depressive symptoms in some patients. Recent evidence suggests that the chronic inflammation may play a role in the pathophysiology of the depressive state, although the specific biological mechanisms are not clear. Herein we describe a model of an inflammation-related depressive phenotype in mice using the tuberculosis vaccine, bacille Calmette-Guerin, to induce chronic inflammation and a subsequent depressive phenotype which is assessed using the tail-suspension test. The model provides an avenue to study not only the molecular and biochemical changes that may be associated with the development of the depressive phenotype, but also pharmacological manipulations of the phenotype. PMID- 26270176 TI - An untargeted global metabolomic analysis reveals the biochemical changes underlying basal resistance and priming in Solanum lycopersicum, and identifies 1 methyltryptophan as a metabolite involved in plant responses to Botrytis cinerea and Pseudomonas syringae. AB - In this study, we have used untargeted global metabolomic analysis to determine and compare the chemical nature of the metabolites altered during the infection of tomato plants (cv. Ailsa Craig) with Botrytis cinerea (Bot) or Pseudomonas syringae pv. tomato DC3000 (Pst), pathogens that have different invasion mechanisms and lifestyles. We also obtained the metabolome of tomato plants primed using the natural resistance inducer hexanoic acid and then infected with these pathogens. By contrasting the metabolomic profiles of infected, primed, and primed + infected plants, we determined not only the processes or components related directly to plant defense responses, but also inferred the metabolic mechanisms by which pathogen resistance is primed. The data show that basal resistance and hexanoic acid-induced resistance to Bot and Pst are associated with a marked metabolic reprogramming. This includes significant changes in amino acids, sugars and free fatty acids, and in primary and secondary metabolism. Comparison of the metabolic profiles of the infections indicated clear differences, reflecting the fact that the plant's chemical responses are highly adapted to specific attackers. The data also indicate involvement of signaling molecules, including pipecolic and azelaic acids, in response to Pst and, interestingly, to Bot. The compound 1-methyltryptophan was shown to be associated with the tomato-Pst and tomato-Bot interactions as well as with hexanoic acid induced resistance. Root application of this Trp-derived metabolite also demonstrated its ability to protect tomato plants against both pathogens. PMID- 26270183 TI - A Simple, Rapid, and Efficient Method for Isolating Mesenchymal Stem Cells From the Entire Umbilical Cord. AB - Several reports have been published on the isolation, culture, and identification of mesenchymal stem cells (MSCs) from different anatomical regions of the umbilical cord (UC). UC is suitable for standardizing methods of MSC isolation because it is a uniform source with high MSC numbers. Although the UC is considered a medical waste after childbirth, ethical issues for its use must be considered. An increased demand for MSCs in regenerative medicine has made scientists prioritize the development of MSC isolation methods. Several research groups are attempting to provide a large number of high-quality MSCs. In this study, we present a modulated explant/enzyme method (MEEM) to isolate the maximum number of MSCs from the entire UC. This method was established for the isolation of MSCs from different anatomical regions of the UC altogether. We could retrieve 6 to 10 million MSCs during 8 to 10 days of primary culture. After three passages, we could obtain 8-10 * 10(8) cells in 28-30 days. MSCs isolated by this method express CD73, CD90, CD105, and CD44, but they do not express hematopoietic markers CD34 and CD45 or the endothelial marker CD31. The genes SOX2, OCT4, and NANOG are expressed in isolated MSCs. The capacity of these MSCs to differentiate into adipocytes and osteocytes highlights their application in regenerative medicine. This method is simple, reproducible, and cost efficient. Moreover, this method is suitable for the production of a large number of high-quality MSCs from an UC in less than a month, to be used for cell therapy in an 80-kg person. PMID- 26270184 TI - Fixation of Zinc(II) Ion to Dioxygen in a Highly Deformed Porphyrin: Implications for the Oxygen Carrier Mechanism of Distorted Heme. AB - Three saddle-type nonplanar zinc porphyrins strapped by two short alkyl linkers have been synthesized. The deformation induced by the linkers can cause a spectral red shift of >30 nm compared with the absorption maxima of regular porphyrins and can also regulate the electronic structure of the central zinc(II) ion. The zinc(II) ion then complexes and activates a free dioxygen to form a superoxide group ligand by enlarging the splitting of energy levels of d orbitals under strong core deformation. The fixation of dioxygen can be reasonably explained by the Dewar-Chatt-Duncanson model. These results indicate that this type of saddle porphyrin has the potential to be used as a new model system of heme. PMID- 26270186 TI - Prognostic Significance of Cutaneous Adverse Events Associated With Pembrolizumab Therapy. PMID- 26270185 TI - Transcriptional Profiling of Endobronchial Ultrasound-Guided Lymph Node Samples Aids Diagnosis of Mediastinal Lymphadenopathy. AB - BACKGROUND: Endobronchial ultrasound (EBUS)-guided biopsy is the mainstay for investigation of mediastinal lymphadenopathy for laboratory diagnosis of malignancy, sarcoidosis, or TB. However, improved methods for discriminating between TB and sarcoidosis and excluding malignancy are still needed. We sought to evaluate the role of genomewide transcriptional profiling to aid diagnostic processes in this setting. METHODS: Mediastinal lymph node samples from 88 individuals were obtained by EBUS-guided aspiration for investigation of mediastinal lymphadenopathy and subjected to transcriptional profiling in addition to conventional laboratory assessments. Computational strategies were used to evaluate the potential for using the transcriptome to distinguish between diagnostic categories. RESULTS: Molecular signatures associated with granulomas or neoplastic and metastatic processes were clearly discernible in granulomatous and malignant lymph node samples, respectively. Support vector machine (SVM) learning using differentially expressed genes showed excellent sensitivity and specificity profiles in receiver operating characteristic curve analysis with area under curve values > 0.9 for discriminating between granulomatous and nongranulomatous disease, TB and sarcoidosis, and between cancer and reactive lymphadenopathy. A two-step decision tree using SVM to distinguish granulomatous and nongranulomatous disease, then between TB and sarcoidosis in granulomatous cases, and between cancer and reactive lymphadenopathy in nongranulomatous cases, achieved > 90% specificity for each diagnosis and afforded greater sensitivity than existing tests to detect TB and cancer. In some diagnostically ambiguous cases, computational classification predicted granulomatous disease or cancer before pathologic abnormalities were evident. CONCLUSIONS: Machine learning analysis of transcriptional profiling in mediastinal lymphadenopathy may significantly improve the clinical utility of EBUS-guided biopsies. PMID- 26270187 TI - Vision loss and paresthesias in a young man. PMID- 26270188 TI - Implicit motor learning is impaired in strabismic adults. AB - Binocular vision disorders (BVD) are quite common in subjects with cerebellar dysfunctions. Also individuals with strabismus often suffer from many motor deficits, such as impaired body balance and walking. It is known that the cerebellum is necessary to maintain proper body posture but also to learn motor skills. It is conceivable that subjects with BVD would also have deficits in procedural (implicit) motor learning, one of the primary cerebellar functions. The primary aim of this study was to explore motor learning abilities in subjects with BVD (strabismic group, SG). Modified versions of a single reaction time task were used in the scheme proposed by Molinari et al. in 1997. A set of three different tasks (Experiment 1) were performed under dominant eye viewing to investigate (a) procedural (implicit) motor learning, (b) declarative (explicit) learning, and (c) simple stimulus-response associative learning. Because each task examined different aspects of motor learning abilities, it could be revealed which motor learning pathway is impaired in SG. Results showed that the SG had slower reaction times in all three tasks and demonstrated poor implicit motor learning ability compared to controls. To verify if these results were caused by reduced binocular vision or cerebellar deficits, per se, a nonstrabismic binocular anomalies group (NSG) was introduced, and all the same tests were performed (Experiment 2). These results revealed that there were no differences between the NSG and the control group with good binocularity. To conclude, the poor procedural learning ability and slower reaction times in strabismic subjects should not be explained as an effect of incomplete binocular vision that influences the maturity of the visual cortex and transformation of visual information into a motor program because binocular anomaly individuals without strabismus have motor learning abilities close to the controls. Some cerebellar deficits appear to be the origin of observed anomalies. PMID- 26270189 TI - Role of early visual cortex in trans-saccadic memory of object features. AB - Early visual cortex (EVC) participates in visual feature memory and the updating of remembered locations across saccades, but its role in the trans-saccadic integration of object features is unknown. We hypothesized that if EVC is involved in updating object features relative to gaze, feature memory should be disrupted when saccades remap an object representation into a simultaneously perturbed EVC site. To test this, we applied transcranial magnetic stimulation (TMS) over functional magnetic resonance imaging-localized EVC clusters corresponding to the bottom left/right visual quadrants (VQs). During experiments, these VQs were probed psychophysically by briefly presenting a central object (Gabor patch) while subjects fixated gaze to the right or left (and above). After a short memory interval, participants were required to detect the relative change in orientation of a re-presented test object at the same spatial location. Participants either sustained fixation during the memory interval (fixation task) or made a horizontal saccade that either maintained or reversed the VQ of the object (saccade task). Three TMS pulses (coinciding with the pre-, peri-, and postsaccade intervals) were applied to the left or right EVC. This had no effect when (a) fixation was maintained, (b) saccades kept the object in the same VQ, or (c) the EVC quadrant corresponding to the first object was stimulated. However, as predicted, TMS reduced performance when saccades (especially larger saccades) crossed the remembered object location and brought it into the VQ corresponding to the TMS site. This suppression effect was statistically significant for leftward saccades and followed a weaker trend for rightward saccades. These causal results are consistent with the idea that EVC is involved in the gaze-centered updating of object features for trans-saccadic memory and perception. PMID- 26270190 TI - Evidence for distinct mechanisms underlying attentional priming and sensory memory for bistable perception. AB - Attentional selection in visual search paradigms and perceptual selection in bistable perception paradigms show functional similarities. For example, both are sensitive to trial history: They are biased toward previously selected targets or interpretations. We investigated whether priming by target selection in visual search and sensory memory for bistable perception are related. We did this by presenting two trial types to observers. We presented either ambiguous spheres that rotated over a central axis and could be perceived as rotating in one of two directions, or search displays in which the unambiguously rotating target and distractor spheres closely resembled the two possible interpretations of the ambiguous stimulus. We interleaved both trial types within experiments, to see whether priming by target selection during search trials would affect the perceptual outcome of bistable perception and, conversely, whether sensory memory during bistable perception would affect target selection times during search. Whereas we found intertrial repetition effects among consecutive search trials and among consecutive bistable trials, we did not find cross-paradigm effects. Thus, even though we could ascertain that our experiments robustly elicited processes of both search priming and sensory memory for bistable perception, these same experiments revealed no interaction between the two. PMID- 26270191 TI - Stretching time: Relativistic lag-induced shifts in perceived audiovisual synchrony using cluttered displays. AB - When presented with temporally displaced audiovisual events, observers shift their point of subjective simultaneity (PSS) in the direction of this prior lag. This effect, known as temporal recalibration (TR), has been inferred previously using single audiovisual events. Here we investigate TR using an audiovisual synchrony search paradigm employing spatiotemporally cluttered visual displays. By manipulating the relative modulation frequency of the adaptor (0.72 Hz) and test (0.36, 0.72 Hz) we find that following lag-adaptation, PSS shifts preserve the relative phase-not the latency-of the adapted lag. Applying this cross frequency design to a classic simultaneity discrimination task, we find TR is unaffected by the relative frequency of adaptor and test in terms of latency rather than phase. This dissociation implies that under conditions of low spatial certainty TR obeys a relativistic (phase-conserving) temporal scaling law, whereas high spatial certainty affords PSS shifts, which operate in absolute (latency-conserving) temporal coordinates. PMID- 26270192 TI - Translation and articulation in biological motion perception. AB - Recent models of biological motion processing focus on the articulational aspect of human walking investigated by point-light figures walking in place. However, in real human walking, the change in the position of the limbs relative to each other (referred to as articulation) results in a change of body location in space over time (referred to as translation). In order to examine the role of this translational component on the perception of biological motion we designed three psychophysical experiments of facing (leftward/rightward) and articulation discrimination (forward/backward and leftward/rightward) of a point-light walker viewed from the side, varying translation direction (relative to articulation direction), the amount of local image motion, and trial duration. In a further set of a forward/backward and a leftward/rightward articulation task, we additionally tested the influence of translational speed, including catch trials without articulation. We found a perceptual bias in translation direction in all three discrimination tasks. In the case of facing discrimination the bias was limited to short stimulus presentation. Our results suggest an interaction of articulation analysis with the processing of translational motion leading to best articulation discrimination when translational direction and speed match articulation. Moreover, we conclude that the global motion of the center-of-mass of the dot pattern is more relevant to processing of translation than the local motion of the dots. Our findings highlight that translation is a relevant cue that should be integrated in models of human motion detection. PMID- 26270193 TI - Conformational Change with Steric Interactions Affects the Inner Sphere Component of Concerted Proton-Electron Transfer in a Pyridyl-Appended Radical Cation System. AB - Proton-coupled electron transfer (PCET) model systems combine one-electron oxidants and bases to generate net hydrogen atom acceptors. We have generated two persistent pyridyl-appended radical cations: 10-(pyrid-2-yl)-10H-phenothiazinium (PPT*+) and 3-(pyrid-2-yl)-10-methyl-10H-phenothiazinium (MPTP*+). EPR spectra and corresponding calculations indicate phenothiazinium radical cations with minimal spin on the pyridine nitrogen. Addition of hindered phenols causes the radical cations to decay, and protonated products and the corresponding phenoxyl radicals to form. The DeltaG degrees values for the formation of intermediates (determined through cyclic voltammetry and pKa measurements) rule out a stepwise mechanism, and kinetic isotope effects support concerted proton-electron transfer (CPET) as the mechanism. Calculations indicate that the reaction of PPT*+ + tBu3PhOH undergoes a significant conformational change with steric interactions on the diabatic surface while maintaining the hydrogen bond; in contrast, MPTP*+ + tBu3PhOH maintains its conformation throughout the reaction. This difference is reflected in both experiment and calculations with DeltaG(?)MPTP*+ < DeltaG(?)PPT*+ despite DeltaG degrees MPTP*+ > DeltaG degrees PPT*+. Experimental results with 2,6-di-tert-butyl-4-methoxyphenol are similar. Hence, despite the structural similarity between the compounds, differences in the inner sphere component for CPET affect the kinetics. PMID- 26270194 TI - Correlation between the Open-Circuit Voltage and Charge Transfer State Energy in Organic Photovoltaic Cells. AB - In order to further improve the performance of organic photovoltaic cells (OPVs), it is essential to better understand the factors that limit the open-circuit voltage (VOC). Previous work has sought to correlate the value of VOC in donor acceptor (D-A) OPVs to the interface energy level offset (EDA). In this work, measurements of electroluminescence are used to extract the charge transfer (CT) state energy for multiple small molecule D-A pairings. The CT state as measured from electroluminescence is found to show better correlation to the maximum VOC than EDA. The difference between EDA and the CT state energy is attributed to the Coulombic binding energy of the CT state. This correlation is demonstrated explicitly by inserting an insulating spacer layer between the donor and acceptor materials, reducing the binding energy of the CT state and increasing the measured VOC. These results demonstrate a direct correlation between maximum VOC and CT state energy. PMID- 26270195 TI - Effect of Protein Concentration on the Flow of Cerebrospinal Fluid Through Shunt Tubing. AB - BACKGROUND: Protein levels in cerebrospinal fluid (CSF) are commonly thought to be related to sterile shunt malfunction. OBJECTIVE: To investigate the relationship between protein concentration and flow through CSF shunt tubing and a shunt valve. METHODS: New and explanted shunt catheters were tested with and without a shunt valve attached at various protein concentrations. The protein concentrations used were 0.5, 2, 5, and 10 g/L. A flask with artificial CSF attached to the proximal end provided flow. The flow was allowed to stabilize over 1 hour, and then the change in pressure between the proximal and distal end of the catheter was measured and recorded. The resistance to flow was calculated for new and explanted catheters for adult shunt systems, as well as with the addition of a programmable siphon control valve. The resistance was examined after the addition of various protein concentrations to a normal CSF solution. RESULTS: Both new and explanted catheters exhibited a decrease in the resistance to flow with higher concentrations of protein. CONCLUSION: In our laboratory setting, there was decreased resistance of adult CSF shunt catheters with and without a valve as the concentration of protein in the CSF increased. The decrease in the resistance of CSF shunt catheters with the addition of protein to the CSF may be related to the lowering of surface tension. This is the first study to examine the effects of varying protein concentrations across different lengths of shunt tubing for both new and explanted catheters. PMID- 26270196 TI - Different Facets in Management of Congenital Atlantoaxial Dislocation and Basilar Invagination. PMID- 26270197 TI - Biocompatible Collagen Paramagnetic Scaffold for Controlled Drug Release. AB - A porous collagen-based hydrogel scaffold was prepared in the presence of iron oxide nanoparticles (NPs) and was characterized by means of infrared spectroscopy and scanning electron microscopy. The hybrid scaffold was then loaded with fluorescein sodium salt as a model compound. The release of the hydrosoluble species was triggered and accurately controlled by the application of an external magnetic field, as monitored by fluorescence spectroscopy. The biocompatibility of the proposed matrix was also tested by the MTT assay performed on 3T3 cells. Cell viability was only slightly reduced when the cells were incubated in the presence of the collagen-NP hydrogel, compared to controls. The economicity of the chemical protocol used to obtain the paramagnetic scaffolds as well as their biocompatibility and the safety of the external trigger needed to induce the drug release suggest the proposed collagen paramagnetic matrices for a number of applications including tissue engeneering and drug delivery. PMID- 26270198 TI - Does Bilateral ITA Grafting Increase Perioperative Complications? Outcome of 6,476 Patients with Bilateral versus 5,020 Patients with Single ITA Bypass. AB - OBJECTIVES: Despite the superior patency of internal thoracic artery (ITA) grafting compared with saphenous veins, frequency of bilateral ITA (BITA) grafting in Europe is still approximately 10%. The aim of the present study was to compare the early outcome of patients receiving either BITA or single ITA (SITA) grafting. METHODS: A total of 11,496 patients with isolated coronary artery bypass grafting (CABG), operated between January 1996 and December 2012, were analyzed retrospectively; 0.6476 patients (mean age 65.2 years, 81.3% males) received BITA and 5,020 patients (mean age 66.6 years, 76.7% males) SITA grafting. Mean body mass index (BMI) was 27.2 versus 27.4, p = 0.017. Incidence of diabetes was 28.9 versus 28.4%, p = 0.08. Ejection fraction (EF) > 50 was 71.3% (BITA) versus 66.3% (SITA), p < 0.001. Elective operations were performed in 88.4% (BITA) versus 83.3% (SITA), and urgent/emergent surgery was necessary in 11.6% (BITA) versus 16.7% (SITA), p < 0.001. RESULTS: Number of grafts was 3.76 (BITA) versus 3.06, p < 0.001. Duration of surgery (194.4 vs. 180.4 minutes) as well as X-clamp time (60.4 vs. 51.7 minutes) was prolonged for BITA, p < 0.001. Perioperative infarction rate revealed 3.2% (BITA) versus 3.6%, p = 0.54. Frequency of rethoracotomy due to bleeding was higher in the BITA group (3.8 vs. 2.1%), p < 0.001. Sternal instabilities occurred in 2.3% (BITA) versus 2.2%, p = 0.749. Duration of mechanical ventilation < 12 hours was 74.6 versus 77.1%, p = 0.09 and duration of in-hospital stay was 10.5 versus 10.4 days, p = 0.68. Thirty day mortality was 2.4% (BITA) versus 3.0%, p = 0.09. Multivariate analysis identified prolonged duration of surgery, BMI > 30, emergent operations, advanced age, and BITA grafting as predictor for sternal instabilities. EF < 30%, advanced age plus emergency were associated with increased 30-day mortality. CONCLUSION: CABG using BITA can be performed routinely with good clinical results and low mortality. Compared with SITA grafting, bleeding complications were enhanced. PMID- 26270200 TI - Acute Effects of Haloperidol, Amisulpride, and Quetiapine on Bone Turnover Markers in Patients With Schizophrenia. AB - OBJECTIVE: This prospective study sought to compare the acute effects of haloperidol, amisulpride, and quetiapine on serum markers of bone formation and resorption in relatively young patients with minimal previous exposure to antipsychotic drugs. METHODS: Patients included in the study were randomly assigned to receive haloperidol, amisulpride, or quetiapine monotherapy in an open-label manner. Serum osteocalcin (OC, a marker of bone formation), C-terminal peptide of type I collagen (CTX, a marker of bone resorption), prolactin (PRL), estradiol, and testosterone were measured in 70 patients at baseline and after 4 weeks of antipsychotic treatment. RESULTS: A repeated-measures analysis of variance revealed a significant difference in CTX levels and in the OC to CTX ratio between treatment groups (F = 4.481, P < 0.05; F = 8.114, P < 0.01). After 4 weeks of treatment, only the amisulpride group had significantly increased CTX levels and decreased OC/CTX. In addition, an obvious increase in PRL level and a reduction of sex hormone secretion after amisulpride treatment were found. No significant changes in bone turnover were observed in the haloperidol or quetiapine groups. Notably, a positive correlation between the CTX change to the change in PRL after treatment (r = 0.255, P < 0.05) was observed. CONCLUSIONS: The PRL-raising antipsychotic drug amisulpride influenced bone turnover balance very early in the course of treatment, which may require long-term monitoring of bone metabolism. Bone resorption marker changes induced by acute antipsychotic drug treatment are likely related to increased PRL levels. PMID- 26270201 TI - Antibiomania: Secondary Mania Associated With Ceftazidime. PMID- 26270199 TI - An Adjusted Calculation Model Allows for Reduced Protamine Doses without Increasing Blood Loss in Cardiac Surgery. AB - Background Heparin dosage for anticoagulation during cardiopulmonary bypass (CPB) is commonly calculated based on the patient's body weight. The protamine-heparin ratio used for heparin reversal varies widely among institutions (0.7-1.3 mg protamine/100 IU heparin). Excess protamine may impair coagulation. With an empirically developed algorithm, the HeProCalc program, heparin, and protamine doses are calculated during the procedure. The primary aim was to investigate whether HeProCalc-based dosage of heparin could reduce protamine use compared with traditional dosages. The secondary aim was to investigate whether HeProCalc based dosage of protamine affected postoperative bleeding. Patients and Methods We consecutively randomized 40 patients into two groups. In the control group, traditional heparin and protamine doses, based on body weight alone, were given. In the treatment group, the HeProCalc program was used, which calculated the initial heparin bolus dose from weight, height, and baseline activated clotting time and the protamine dose at termination of CPB. Results We analyzed the results from 37 patients, after exclusion of three patients. Equal doses of heparin were given in both groups, whereas significantly lower mean doses of protamine were given in the treatment group versus control group (211 +/- 56 vs. 330 +/- 61 mg, p < 0.001). Postoperative bleeding was less in the HeProCalc group (280 +/- 229 mL) as compared with the control group (649 +/- 279 mL). However, this difference was not found statistically significant (p = 0.074). Conclusion HeProCalc-based dosage of heparin and protamine allowed for reduced protamine use after CPB compared with when conventional calculations were used. Furthermore, HeProCalc-based regimen for heparin reversal suggested less postoperative bleeding, although the difference between the groups was not statistically significant. PMID- 26270202 TI - Ba and Sr Binary Phosphides: Synthesis, Crystal Structures, and Bonding Analysis. AB - Synthesis, crystal structures, and chemical bonding are reported for four binary phosphides with different degrees of phosphorus oligomerization, ranging from isolated P atoms to infinite phosphorus chains. Ba3P2 = Ba4P(2.67)?(0.33) (? = vacancy) crystallizes in the anti-Th3P4 structure type with the cubic space group I43d (no. 220), Z = 6, a = 9.7520(7) A. In the Ba3P2 crystal structure, isolated P(3-) anions form distorted octahedra around the Ba(2+) cations. beta-Ba5P4 crystallizes in the Eu5As4 structure type with the orthorhombic space group Cmce (no. 64), Z = 4, a = 16.521(2) A, b = 8.3422(9) A, c = 8.4216(9) A. In the crystal structure of beta-Ba5P4, one-half of the phosphorus atoms are condensed into P2(4-) dumbbells. SrP2 and BaP2 are isostructural and crystallize in the monoclinic space group P21/c (no. 14), Z = 6, a = 6.120(2)/6.368(1) A, b = 11.818(3)/12.133(2) A, c = 7.441(2)/7.687(2) A, beta = 126.681(4)/126.766(2) degrees for SrP2/BaP2. In the crystal structures of SrP2 and BaP2, all phosphorus atoms are condensed into infinity(1)P(1-) cis-trans helical chains. Electronic structure calculations, chemical bonding analysis via the recently developed solid-state adaptive natural density partitioning (SSAdNDP) method, and UV-vis spectroscopy reveal that SrP2 and BaP2 are electron-balanced semiconductors. PMID- 26270203 TI - The Serendipitous Survey: A Look at Primary and Specialist Palliative Social Work Practice, Preparation, and Competence. AB - BACKGROUND: Health professionals have begun to identify competencies needed for primary and specialist levels of palliative care practice, but little attention has been given to how these skills are acquired. OBJECTIVES: The authors electronically surveyed a wide range of health social workers and educators to investigate their reported levels of preparation, training, and self-assessed competence to provide palliative and end-of-life care. METHODS: Two health social work surveys were developed: one for educators and one for practitioners and students. The study used an electronic snowball sampling method with eight national social work listservs to capture a wide range of settings where health social workers may teach or practice. The survey was completed by 1149 self identified health care social workers, 35% of whom identified as a specialist in palliative care. RESULTS: Health social work clinicians report competence in many skills related to palliative care and the psychosocial determinants of health, having developed these skills primarily through interprofessional and peer collaboration. CONCLUSIONS: A representative sample of social workers practicing in health care identify high competence in essential aspects of palliative care. This speaks to an existing pool of clinicians who, if practicing to the top of their licenses, have the potential to provide primary palliative care and contribute to the person-family centered care called for in the Institute of Medicine (IOM) report. Few programs exist to prepare social workers to work as specialists in palliative or end-of-life settings, and respondents identified key areas of practice that need to be integrated into graduate education to ensure that students, practitioners, and educators are better prepared to maximize the impact of health social work. Further research is needed to better understand how to prepare and train specialist-level palliative care social workers. PMID- 26270204 TI - Insulin Resistance in Critically Injured Adults: Contribution of Pneumonia, Diabetes, Nutrition, and Acuity. AB - PURPOSE: Changes in insulin resistance (IR) cause stress-induced hyperglycemia after trauma, but the numerous factors involved in IR have not been delineated clearly. We hypothesized that a statistical model could help determine the relative contribution of different clinical co-variates to IR in critically injured patients. PATIENTS AND METHODS: We retrospectively studied 726 critically injured patients managed with a computer-assisted glycemic protocol at an academic level I trauma center (639 ventilated controls without pneumonia (VWP) and 87 patients with ventilator-associated pneumonia (VAP). Linear regression using age, gender, body mass index (BMI), diabetes mellitus, pneumonia, and glycemic provision was used to estimate M, a marker of IR that incorporates both the serum blood glucose concentration (BG) and insulin dose. RESULTS: Increasing M (p<0.001) was associated with age (1.62%; 95% confidence interval [CI] 1.27% 1.97% per decade), male gender (9.78%; 95% CI 8.28%-12.6%), BMI (4.32% [95% CI 4.02%-4.62%] per 5 points), diabetes mellitus (21.2%; 95% CI 19.2%-23.2%), pneumonia (10.9%; 95% CI 9.31%-12.6%), and glycemic provision (27.3% [95% CI 6.6% 28.1%] per 100 g of glucose). Total parenteral nutrition was associated with a decrease in M of 10.3%; 95% CI 8.52%-12.1%; p<0.001. CONCLUSIONS: Clinical factors can be used to construct a model of IR. Prospective validation might enable early detection and treatment of infection or other conditions associated with increased IR. PMID- 26270205 TI - Effect of Insulin Dilution on Lowering Glycemic Variability in Pump-Treated Young Children with Inadequately Controlled Type 1 Diabetes. AB - BACKGROUND: We investigated whether in young children with inadequately controlled type 1 diabetes and technical problems with continuous subcutaneous infusion of insulin at 100 units/mL the switch to insulin diluted to 10 units/mL (U10) can limit technical problems and improve glycemic control. SUBJECTS AND METHODS: Diluted U10 insulin was started in three children 3.8, 3.2, and 1.3 years old with a hemoglobin A1c (HbA1c) level (mean+/-SD) of 8.1+/-0.17% (65+/ 1.7 mmol/mol) and insulin dose of 8.80+/-2.93 units/day. Patients were evaluated with continuous glucose monitoring (iProTM2; Medtronic Minimed, Northridge, CA) and a quality of life questionnaire (PedsQLTM; www.pedsql.org/ ) and surveyed for pump-related problems at baseline and after 3 and 9 months of U10 insulin therapy. RESULTS: Continuous glucose monitoring records showed that glycemic variability assessed by SD and M100 decreased significantly (P=0.0085 and P=0.0482, respectively). HbA1c levels dropped to 7.3+/-1.00% (56+/-11.0 mmol/mol) after 3 months and to 6.7+/-0.55% (50+/-6.1 mmol/mol) after 9 months (P=0.12). Technical difficulties were minimized. CONCLUSIONS: These results suggest that the use of U10 insulin decreases glycemic variability and improves hampered pump therapy in young children with inadequately controlled type 1 diabetes. PMID- 26270206 TI - Transarterial chemoembolization and sorafenib in patients with intermediate-stage hepatocellular carcinoma: time to enter routine clinical practice? PMID- 26270207 TI - History of water quality parameters - a study on the Sinos River/Brazil. AB - Water is increasingly becoming a valuable resource, constituting one of the central themes of environmental, economic and social discussions. The Sinos River, located in southern Brazil, is the main river from the Sinos River Basin, representing a source of drinking water supply for a highly populated region. Considering its size and importance, it becomes necessary to conduct a study to follow up the water quality of this river, which is considered by some experts as one of the most polluted rivers in Brazil. As for this study, its great importance lies in the historical analysis of indicators. In this sense, we sought to develop aspects related to the management of water resources by performing a historical analysis of the Water Quality Index (WQI) of the Sinos River, using statistical methods. With regard to the methodological procedures, it should be pointed out that this study performs a time analysis of monitoring data on parameters related to a punctual measurement that is variable in time, using statistical tools. The data used refer to analyses of the water quality of the Sinos River (WQI) from the State Environmental Protection Agency Henrique Luiz Roessler (Fundacao Estadual de Protecao Ambiental Henrique Luiz Roessler, FEPAM) covering the period between 2000 and 2008, as well as to a theoretical analysis focusing on the management of water resources. The study of WQI and its parameters by statistical analysis has shown to be effective, ensuring its effectiveness as a tool for the management of water resources. The descriptive analysis of the WQI and its parameters showed that the water quality of the Sinos River is concerning low, which reaffirms that it is one of the most polluted rivers in Brazil. It should be highlighted that there was an overall difficulty in obtaining data with the appropriate periodicity, as well as a long complete series, which limited the conduction of statistical studies such as the present one. PMID- 26270208 TI - Adenoviruses of canine and human origins in stool samples from free-living pampas foxes (Lycalopex gymnocercus) and crab-eating foxes (Cerdocyon thous) in Sao Francisco de Paula, Rio dos Sinos basin. AB - The spread of enteric viruses of domestic animals and human beings to wild species can be facilitated by the resistance of these viruses on the environment and their ability to be transmitted by water and contaminated food. The health status of the populations of pampas foxes Lycalopex gymnocercus) and crab-eating foxes (Cerdocyon thous) is largely unknown and the landscapes occupied by these animals in southern Brazil have been threatened by human occupation and expansion of agriculture. In this work, the search of genomes of human and canine adenoviruses in feces from these wild carnivores was used to track the dissemination of domestic animals and human pathogens to the free-living populations in a wildlife reserve located in southern Brazil. This was performed by virus-specific differential real-time polymerase chain reactions (qPCR) on stool specimens, avoiding capture and additional stress to the animals. Genus specific conventional reverse-transcriptase PCR (RT-PCR) was complementarily performed aiming the detection of enteroviruses (EV) and rotaviruses (RV) on these same samples. HAdV genomes were found on 14 out of the 17 (82.35%) stool samples analysed, whereas CAV was found co-infecting 5 of these samples. RV genomes were detected on 7 of the 17 samples (41.18%) and all samples were negative for EV. The results point to the dispersion of HAdV and RV at a high rate to these species of South American wild carnivores, which can be an effect of growing anthropisation of the habitat of these animals. PMID- 26270210 TI - Vascular epiphytes of the Atlantic Forest in the Sinos River basin, state of Rio Grande do Sul, Brazil: richness, floristic composition and community structure. AB - The Atlantic Forest, which has a vast epiphytic richness, is a priority area for preservation, listed as one of the five most important world hotspots. Vascular epiphyte richness, composition and community structure were studied in two fragments, one of the ombrophilous (29o43'42"S and 50o22'00"W) and the other of the seasonal (29o40'54"S and 51o06'56"W) forest, both belonging to the Atlantic Forest biome in the Sinos River basin, Rio Grande do Sul, Brazil. In each fragment, 40 trees, divided into four ecological zones, were analyzed. In each zone, the occurrence of the species was recorded, and the importance value of each species was calculated according to the frequency of phorophytes and intervals, and cover scores. The Shannon index was calculated for the two communities. In the fragment of the ombrophilous forest (F1), 30 epiphytic species were recorded, and in the seasonal forest (F2), 25. The highest importance value was found for Microgramma squamulosa (Kaulf.) de la Sota in both fragments. The diversity indexes for F1 (H'=2.72) and F2 (H'=2.55) were similar and reflected the subtropical location of the areas. The decrease in mean richness in both fragments in zone 3 (internal crown) to zone 4 (external crown) may be associated with time and space availability for epiphyte occupation and microclimate variations. Exclusive species were found in the areas, which suggest that a greater number of preserved fragments may result in a greater number of preserved epiphytic species in the Sinos River basin. PMID- 26270211 TI - The effects of press and pulse disturbance by long and short-term pollution on the fish community in the Sinos River, RS, Brazil. AB - The fish fauna of the Sinos River has been subjected to severe pollution since the 1970's. Continuous discharges of industrial and municipal sewage cause hypoxia and often even fish kills. The objectives of the present study are to assess long-term effects of pollution on the fish community over a time scale of approximately ten years and to investigate recuperation of the fish fauna after a massive fish kill in 2006. To assess the long-term impacts, seasonal sampling was conducted from September 2007 to March 2009 in four sites which were investigated in 1998/99 with the same methodology. The effects of the fish kill were investigated by comparing the present fauna in the affected river stretch with the fauna of an unaffected adjacent river stretch. The collective community properties richness and Shannon diversity changed during the ten year interval in a consistent pattern. Richness and Shannon diversity increased significantly in all sites, abundance values, however, did not. Analysis of species constancy and cluster analysis showed that the differences between the 1998/99 and 2007/09 studies were relatively small. The comparison of the reaches affected by the 2006 fish kills showed a rapid recovery within one year. Probably the Sinos fish fauna suffered the most severe impacts in the 70s of the last century, which could not be documented by this study. After an initial decline, the community displays relatively stable patterns with a tendency of recovery. After a severe fish kill, faunal recovery was rapid, probably favoured by the proximity of unpolluted source areas and physical habitat integrity of the Sinos River. PMID- 26270209 TI - Toxicity effects of nickel electroplating effluents treated by photoelectrooxidation in the industries of the Sinos River Basin. AB - The Sinos river Basin is an industrial region with many tanneries and electroplating plants in southern Brazil. The wastewater generated by electroplating contains high loads of salts and metals that have to be treated before discharge. After conventional treatment, this study applied an advanced oxidative process to degrade organic additives in the electroplating bright nickel baths effluent. Synthetic rinsing water was submitted to physical-chemical coagulation for nickel removal. The sample was submitted to ecotoxicity tests, and the effluent was treated by photoelectrooxidation (PEO). The effects of current density and treatment time were evaluated. The concentration of total organic carbon (TOC) was 38% lower. The toxicity tests of the effluent treated using PEO revealed that the organic additives were partially degraded and the concentration that is toxic for test organisms was reduced. PMID- 26270212 TI - Degradation of cyanotoxins (microcystin) in drinking water using photoelectrooxidation. AB - The discharge of sewage and industrial effluents containing high concentrations of pollutants in water bodies increases eutrophication. Cyanobacteria, some of the organisms whose growth is promoted by high nutrient concentrations, are resistant and produce several types of toxins, known as cyanotoxins, highly harmful to human beings. Current water treatment systems for the public water supply are not efficient in degradation of toxins. Advanced oxidation processes (AOP) have been tested for the removal of cyanotoxins, and the results have been positive. This study examines the application of photoelectrooxidation in the degradation of cyanotoxins (microcystins). The performance of the oxidative processes involved was evaluated separately: Photocatalysis, Electrolysis and Photoelectrooxidation. Results showed that the electrical current and UV radiation were directly associated with toxin degradation. The PEO system is efficient in removing cyanotoxins, and the reduction rate reached 99%. The final concentration of toxin was less than 1 ug/L of microcystin in the treated solution. PMID- 26270213 TI - Monitoring of metals, organic compounds and coliforms in water catchment points from the Sinos River basin. AB - Unplanned use and occupation of the land without respecting its capacity of assimilation and environmental purification leads to the degradation of the environment and of water used for human consumption. Agricultural areas, industrial plants and urban centres developed without planning and the control of effluent discharges are the main causes of water pollution in river basins that receive all the liquid effluents produced in those places. Over the last decades, environmental management has become part of governmental agendas in search of solutions for the preservation of water quality and the restoration of already degraded resources. This study evaluated the conditions of the main watercourse of the Sinos River basin by monitoring the main physical, chemical and microbiological parameters described in the CONAMA Resolution no. 357/2005.The set of parameters evaluated at five catchment points of water human consumption revealed a river that has different characteristics in each reach, as the upper reach was class 1, whereas the middle and lower reaches of the basin were class 4. Monitoring pointed to households as the main sources of pollutants in those reaches, although metals used in the industrial production of the region were found in the samples analyzed. PMID- 26270214 TI - Evaluation of phytotoxicity of municipal landfill leachate before and after biological treatment. AB - In the present study, leachate toxicity of a municipal solid waste landfill located in the Sinos River Valley region (southern Brazil) was evaluated using plant bioassays. Leachate toxicity was assessed by analysis of seed germination and root elongation of lettuce (Lactuca sativa L.) and rocket plant Eruca sativa Mill.) and root elongation of onions Allium cepa L.). Bioassays were performed by exposing the seeds of L. sativa and E. sativa and the roots of A. cepa to raw leachate, treated leachate (biological treatment) and negative control (tap water). The levels of metals detected in both samples of leachate were low, and raw leachate showed high values for ammoniacal nitrogen and total Kjeldahl nitrogen. There is a reduction in the values of several physicochemical parameters, which demonstrates the efficiency of the treatment. Both L. sativa and A. cepa showed a phytotoxic response to landfill leachate, showing reduced root elongation. However, the responses of these two plant species were different. Root elongation was significantly lower in A. cepa exposed to treated leachate, when compared to negative control, but did not show any difference when compared to raw leachate. In L. sativa, seeds exposed to the raw leachate showed significant reduction in root elongation, when compared to treated leachate and negative control. Seed germination showed no difference across the treatments. The results of the study show that plant species respond differently and that municipal solid waste landfill leachate show phytotoxicity, even after biological treatment. PMID- 26270215 TI - Moving beyond classical markers of water quality: detection of enteric viruses and genotoxicity in water of the Sinos River. AB - It is well recognized that the classical biological and chemical markers of environmental pollution do not necessarily indicate the presence or absence of emerging threats to public health, such as waterborne viruses and genotoxicants. The purpose of this preliminary study was to evaluate the presence of material of enteroviruses (EV), rotavirus (RV) and adenovirus (AdV) and genotoxicity in water samples from points of routine monitoring of water quality in the main course of the Sinos River. The points are classified into different levels of pollution in accordance to the Brazilian federal regulations. Viral genomes from EV, AdV were detected in two of the 4 collection points regardless of the level of urbanisation of the surrounding areas. In contrast, genotoxicity was not observed in piava (Leporinus obtusidens) fingerlings cultivated on these same water samples. Results were compared with classical physical, chemical and microbiological parameters. There was no clear evidence of association between any of the classical markers and the presence of viral genomes in the water samples tested. PMID- 26270216 TI - Evaluation of genotoxicity and cytotoxicity of water samples from the Sinos River Basin, southern Brazil. AB - Some water bodies in the Sinos River Basin (SRB) have been suffering the effects of pollution by residential, industrial and agroindustrial wastewater. The presence of cytotoxic and genotoxic compounds could compromise the water quality and the balance of these ecosystems. In this context, the research aimed to evaluate the genotoxicity and cytotoxicity of the water at four sites along the SRB (in the cities of Santo Antonio da Patrulha, Parobe, Campo Bom and Esteio), using bioassays in fish and cell culture. Samples of surface water were collected and evaluated in vitro using the Astyanax jacuhiensis fish species (micronucleus test and comet assay) and the Vero lineage of cells (comet assay and cytotoxicity tests, neutral red - NR and tetrazolium MTT). The micronucleus test in fish showed no significant differences between the sampling sites, and neither did the comet assay and the MTT and NR tests in Vero cells. The comet assay showed an increase in genetic damage in the fish exposed to water samples collected in the middle and lower sections of the basin (Parobe, Campo Bom and Esteio) when compared to the upper section of the basin (Santo Antonio da Patrulha). The results indicate contamination by genotoxic substances starting in the middle section of the SRB. PMID- 26270217 TI - Cytotoxicity assays as tools to assess water quality in the Sinos River basin. AB - Cytotoxicity assays using cell cultures may be an alternative to assess biological toxicity of surface waters and may help to improve the control of water quality. This study compared two methods to prepare culture media for the exposure of Hep-2 cells to water samples collected from the Rolante River, an important affluent of the Sinos River. The toxicity was evaluated using the MTT and neutral red assays. Two methods were used to prepare culture media. In method 1, the sample was diluted at 1:1, 1:10, 1:100, 1:1000, 1:10.000 (v/v, sample/medium) in a standard culture medium; in method 2, water samples were used as the solvent for the culture medium, which was prepared at concentrations of 100, 80, 60, 40 and 20%. Semi-confluent cultures were then exposed to the media test for 24 hours, and cytotoxicity was determined immediately using the MTT and NR assays. Mitochondrial activity (MTT) was significantly lower at all concentrations in both methods, except at 1:1000 in method 1. However, the lysosome viability (NR) results revealed cytotoxicity only in the 1:1 sample of method 1. Both culture preparation methods were efficient and sensitive to the MTT assay, but method 2 seemed to be more adequate for the NR assay. The Rolante River has cytotoxic contaminants to Hep-2 cells, which may be one of the explanations for the poor water quality of the Sinos River basin. PMID- 26270218 TI - Caffeine as an indicator of human fecal contamination in the Sinos River: a preliminary study. AB - The preservation of hydric resources is directly related to fecal contamination monitoring, in order to allow the development of strategies for the management of polluting sources. In the present study, twenty-five water samples from six water public supply collection sites were used for the evaluation of the presence of caffeine, total and fecal coliforms. Caffeine was detected in all samples, with concentrations ranging from 0.15 ng mL-1 to 16.72 ng mL-1. Total coliforms were detected in all samples, with concentrations in the range of 52 NMP/100 mL to higher than 24196 NMP/100 mL, whether the concentration range for fecal coliforms was in the range of below 1 NMP/100 mL to 7800 NMP/100 mL. No significant correlation was found between total coliforms and caffeine concentrations (rs = 0.35, p = 0.09). However, a moderate correlation between fecal coliforms and caffeine concentrations was found (rs = 0.412, p <0.05), probably indicating a human source for these bacteria. Caffeine determination in water may be a useful strategy to evaluate water contamination by human fecal waste. PMID- 26270219 TI - Endocrine disruptors in water filters used in the Rio dos Sinos Basin region, Southern Brazil. AB - The activated carbon filter is used in residences as another step in the treatment of drinking water, based on a physical-chemical process to absorb pollutants that are not removed in conventional treatment. Endocrine disruptors (EDCs) are exogenous substances or mixtures of substances that acts on the endocrine system similarly to the endogenously produced hormones, triggering malfunctions and harmful changes to human and animal health. The objective of the present work was to study EDCs through semi-quantitative analysis of residential water filters collected in the region of Rio dos Sinos basin, focusing on two specific classes: hormones and phenols. The solid phase extraction principle was used for the extraction of compounds and gas chromatography coupled with mass spectrometry for the separation and characterization of EDCs. Four samples of residential filters collected from public water distribution and artesian wells, from the cities of Novo Hamburgo and Sao Leopoldo were analysed. Using the developed methodology, it was possible to detect and comparatively quantify selected EDCs in all studied samples, which indicates the presence of these contaminants in drinking water from different sources. PMID- 26270220 TI - Biomonitoring of water genotoxicity in a Conservation Unit in the Sinos River Basin, Southern Brazil, using the Tradescantia micronucleus bioassay. AB - The Tradescantia micronucleus (Trad-MCN) bioassay was used to investigate genotoxicity of water bodies in the Parque Municipal Henrique Luis Roessler (PMHLR), a conservation unit in the city of Novo Hamburgo, Southern Brazil, from November 2010 to October 2011. Every month, cuttings with young inflorescences of Tradescantia pallida var. purpurea were exposed for 24 hours to water collected at three sites in the park: (S1) head of the main stream; (S2) head of a secondary stream; (S3) a point past the junction of the two water bodies in which S1 and S2 were located. As a negative control, cuttings were exposed to distilled water for 24 h every quarter. Micronuclei (MCN) frequency was determined in young tetrads of pollen mother cells and described as MCN/100 tetrads. Rainfall data were also recorded. In nine months at S1 and S2, and in eleven months at S3, micronuclei frequencies were significantly higher than in quarterly controls, in which frequencies varied from 1.19 to 1.62. During sampling, no significant differences were found in MCN frequencies at S1, which ranged from 2.2 to 3.6. At the other sampling sites, there were significant differences between the months evaluated, and MCN frequencies ranged from 1.3 to 6.5 at S2 and from 2.3 to 5.2 at S3. There were no associations between rainfall and MCN frequencies at the three sampling sites. Tradescantia pallida var. purpurea confirmed genotoxicity in the water bodies of the PMHLR, even at the head of the streams, which suggests that actions should be promoted to control anthropogenic effects in the streams of this conservation unit. PMID- 26270221 TI - Evaluation of water quality at the source of streams of the Sinos River Basin, southern Brazil. AB - The Sinos River Basin (SRB) is located in the northeastern region of the state of Rio Grande do Sul (29o20' to 30o10'S and 50o15' to 51o20'W), southern Brazil, and covers two geomorphologic provinces: the southern plateau and the central depression. It is part of the Guaiba basin, has an area of approximately 800 km 2 and contains 32 counties. The basin provides drinking water for 1.6 million inhabitants in one of the most important industrial centres in Brazil. This study describes different water quality indices (WQI) used for the sub-basins of three important streams in the SRB: Pampa, Estancia Velha/Portao and Schmidt streams. Physical, chemical and microbiological parameters assessed bimonthly using samples collected at each stream source were used to calculate the Horton Index (HI), the Dinius Index (DI) and the water quality index adopted by the US National Sanitation Foundation (NSF WQI) in the additive and multiplicative forms. These indices describe mean water quality levels at the streams sources. The results obtained for these 3 indexes showed a worrying scenario in which water quality has already been negatively affected at the sites where three important sub-basins in the Sinos River Basin begin to form. PMID- 26270222 TI - Integrated Environmental Assessment of streams in the Sinos River basin in the state of Rio Grande do Sul, Brazil. AB - The deterioration of environmental quality in the Sinos River basin is directly associated with the impacts of intense industrialization and urbanization. An integrated environmental assessment (IEA) was conducted in July and September of 2012, in areas along the sources of the EstanciaVelha/Portao, Pampa and Schmidt streams using physical, chemical and biological methods. The water in the three sampling sites was not proper for human consumption, presented a low toxic contamination index (TCI) and mesotrophic characteristics. One site was included in Class 4, and two, in Class 3, according to current legislation. The rapid assessment protocol (RAP) indicated a natural environmental condition for habitat diversity and environmental impact in the three sites. The Tradescantia pallida (Rose) D.R. Hunt var. purpurea Boom biomarker showed water genotoxicity in two of the sites. The integrated diagnosis of water quality in these streams is fundamentally important to ensure the sustainable management of water resources and their multiple uses, as well to estimate their contribution to pollution in this river basin. PMID- 26270224 TI - Corporate governance and proactive environmental management in Novo Hamburgo and neighbouring cities, Brazil. AB - This study compiled data on environmental auditing and voluntary certification of environment-friendly businesses of the Commercial and Industrial Association of Novo Hamburgo, Campo Bom and Estancia Velha and analysed them according to classical environmental management principles: sustainable development and corporate governance. It assessed the level of application of the concepts of corporate governance to everyday business in companies and organisations and estimated how the interconnection and vertical permeability of these concepts might help to make bureaucratic environmental management systemic, proactive and evaluative, changes that may add great value to the operations evaluated. Results showed that, when analysing only audited items not directly defined in legislation, no significant changes were identified. The inclusion of more advanced indices may promote the transition from bureaucratic management, which meets regulated environmental standards only satisfactorily, into proactive and systemic environmental management, which adds value to companies and helps to perpetuate them. Audited and analysed data did not reveal actions that depend on the internal redistribution of power and the interconnection or verticality of attitudes that may materialize concepts of corporate governance. PMID- 26270223 TI - Games in the environmental context and their strategic use for environmental education. AB - This article aims to present the productivity of the assumptions of Philosophical Hermeneutics (Gadamer, 1996) and his discovery of the logical, ontological and structural model of the game that takes place during the experience that is the basis of comprehension. Thus, digital games are proposed as manners, methods and ways to improve the understanding, interpretation and application of the concepts of Sustainability and Environmental Principles. The attraction of the game as a pedagogic space lays in the fact that it takes over and allows the player to internalize ecological sensitivity, something that happens during the play. Finally, the results show an augment on students' motivation, when using the game versus the traditional process. PMID- 26270225 TI - Environment and society: the Sinos River Basin and public policies. AB - This study discusses the tensions and conflicts in the relationship between environment and society in the Sinos River Basin, in the state of Rio Grande do Sul, Brazil. An environmental disaster in 2006, which resulted in the death of 100 tons of fish in the Sinos River, is the dividing line for this study. A review of documents and field interviews with representatives of the municipal government and companies in the region were used to analyze the impact of public policies on the environment and which deficiencies remain. PMID- 26270226 TI - Editorial note. PMID- 26270227 TI - Editorial note. PMID- 26270228 TI - Extraction, purification and characterization of the crystallin protein of cataractous eye lens nucleus. AB - The purpose of this study is to separate and identify the crystallin protein present in the nucleus of a human cataractous eye lens. Cataractous lenses were collected from different eye hospitals from patients of different etiologies with ages between 40 and 80 years. Lens nucleus proteins were extracted into four fractions on the basis of their solubility in different media by applying a reported method. These fractions were buffer-soluble proteins (PS), urea-soluble proteins (PU), yellow fraction proteins (PY) and insoluble proteins (PI). All three soluble fractions were subjected to HPLC and GPC analysis. Both HPLC and GPC analysis showed that each fraction contains alpha-, beta- and gamma crystallins, a major class of protein present in the lenses of vertebrates. Various chromatographic parameters including precision, accuracy and linearity have been evaluated. Studies of water-insoluble crystallins using sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE) have demonstrated extreme homogeneity with evidence of major components with molecular masses of 18 70 kDa, similar to the crystallin of the water-soluble portion. The method was found to be suitable for the analysis of various isomers of crystallin protein present in human cataractous eye lens nuclei. The detailed results of the GPC are discussed. This study provides the first HPLC and GPC analysis of a human cataractous eye lens nucleus. PMID- 26270229 TI - Parathyroid Hormone Plus Alendronate in Osteoporosis: A Meta-Analysis of Randomized Controlled Trials. AB - BACKGROUND: Parathyroid hormone (PTH) increases both bone formation (BMD) and bone resorption, whereas alendronate reduces bone resorption. It is possible that the combination therapy will enhance their effects on BMD. Therefore, we conducted this meta-analysis to evaluate the efficacy of the combination therapy in osteoporosis. METHODS: A comprehensive literature search of Pubmed, Embase, and Web of Science was conducted to identify relative studies. The outcomes included the mean percent increases in BMD of lumbar spine, femoral neck, total hip, and distal radius. A fixed-effects model or random-effects was used to pool the estimates according to the heterogeneity. RESULTS: Six RCTs with a total number of 833 patients were included in this meta-analysis. The pooled estimates showed that, the combination therapy resulted in a higher mean percent change of increased BMD in distal radius (WMD = 2.45, 95%CI: 1.58, 3.31; 0.000), but not in lumbar spine (WMD = -0.83, 95%CI: -3.48, 1.81; p = .538), femoral neck (WMD = 0.99, 95%CI: -2.04, 0.07; p = .068), and total hip (WMD = -0.06, 95%CI: -0.93, 0.81; p = .892). Subgroup analysis revealed that among the patients in the combination therapy group, greater increases in the spine BMD were observed when the PTH was administered with a dosage of 20 MUg (WMD = 2.33, 95%CI: 1.24, 3.43; p = .000), or the treatment duration lasted more than 12 months (WMD = 2.23, 95%CI: 1.00, 3.47; p = .000), or the combination therapy was used in osteoporosis women (WMD = 1.58, 95%CI: 0.63, 2.53; p = .001). CONCLUSION: Our findings indicated that combination therapy in the treatment of osteoporosis, reduced the ability of PTH therapy to increase the BMD at the lumbar spine, femoral neck, and total hip. PMID- 26270230 TI - Issues Pertaining to Monitoring the Abuse of Amphetamines in Workplace Drug Testing. AB - Literature pertaining to three potential problematic areas in forensic drug urinalysis of amphetamines is reviewed. The first topic involves analytical artifacts causing false positive results for methamphetamine, as well as approaches to instrumental and chemical resolutions. The second topic addresses enantiomeric compositions, including sources, analytical approaches, metabolic mechanisms, and interpretation criteria. The third topic is concerned with legal and illicit drugs that may produce amphetamine or methamphetamine as metabolites, and relevant information regarding interpretation of these results. PMID- 26270231 TI - The Scientific Examination of Chinese Handwriting. AB - The Chinese character, invented about 4,000 years ago, was based on an idiographic concept, eight basic strokes arranged two dimensionally forming the essential building components of the character. As a result of the complex structure, there are many different ways of writing a Chinese character. Therefore, in determining authorship of Chinese handwriting, there are many factors that have to be considered. It is necessary for the examiner to distinguish between class characteristics and individual characteristics. There are generally three common styles of Chinese handwriting: the regular style; the running style; and the cursive style, which can either be written in the orthodox form or the simplified form. On the other hand, individual or personal characteristics can be categorized into measurable parameters and qualitative parameters. Apart from these, there are complications involving the writer himself. Disguise and writing speed are considered to be particularly important in constituting interference to the examination process. All those enumerated here are critically reviewed in this paper. In addition, discussions on the examination of Chinese signatures, the expression of opinion, other contributing factors, and future developments on Chinese handwriting examination are discussed. PMID- 26270234 TI - Construction of benzo-fused indolizines, pyrrolo[1,2-a]quinolines via alkyne carbonyl metathesis. AB - The strategic use of a sequential Sonogashira coupling/intramolecular alkyne carbonyl metathesis process for the synthesis of a pyridine ring from 1-(2 haloaryl)-1H-pyrrole-2-carbaldehydes allowed ready access to diverse novel benzo fused indolizines, pyrrolo[1,2-a]quinolines, in good to excellent yields. As a hybrid structure of indolizine and quinoline, the resulting scaffold has an acyl substituent at the C5 position, which is difficult to make by any other known approaches. PMID- 26270233 TI - Magnetically Self-Assembled Colloidal Three-Dimensional Structures as Cell Growth Scaffold. AB - Understanding the chemical and physical conditions for cell growth is important from biological and medical aspects. Many tissues and cell types (e.g., epithelial cells and neurons) naturally grow on surfaces that span in three dimensions and offer structural or mechanical support. The scaffold surface has to promote adhesion and cell proliferation as well as support their weight and retain its structural integrity. Here, we present a flexible method that uses self-assembly of micrometer superparamagnetic particles to produce appropriate scaffold surfaces with controllable general appearance in three dimensions, such as oriented membranes, branched structure, or void network. As a proof of principle, the Chinese hamster ovary epithelial cell line was successfully grown for several days on inclined membranes. Robustness of the oriented membrane architecture was probed with optical tweezers. We measured the magnetic force holding one particle in a self-assembled upright hexagonal sheet and modeled it as a sum of pair interaction forces between spatially arrested static dipoles. PMID- 26270235 TI - Vanadium-based nanostructure materials for secondary lithium battery applications. AB - Vanadium-based materials, such as V2O5, LiV3O8, VO2(B) and Li3V2(PO4)3 are compounds that share the characteristic of intercalation chemistry. Their layered or open frameworks allow facile ion movement through the interspaces, making them promising cathodes for LIB applications. To bypass bottlenecks occurring in the electrochemical performances of vanadium-based cathodes that derive from their intrinsic low electrical conductivity and ion diffusion coefficients, nano engineering strategies have been implemented to "create" newly emerging properties that are unattainable at the bulk solid level. Integrating this concept into vanadium-based cathodes represents a promising way to circumvent the aforementioned problems as nanostructuring offers potential improvements in electrochemical performances by providing shorter mass transport distances, higher electrode/electrolyte contact interfaces, and better accommodation of strain upon lithium uptake/release. The significance of nanoscopic architectures has been exemplified in the literature, showing that the idea of developing vanadium-based nanostructures is an exciting prospect to be explored. In this review, we will be casting light on the recent advances in the synthesis of nanostructured vanadium-based cathodes. Furthermore, efficient strategies such as hybridization with foreign matrices and elemental doping are introduced as a possible way to boost their electrochemical performances (e.g., rate capability, cycling stability) to a higher level. Finally, some suggestions relating to the perspectives for the future developments of vanadium-based cathodes are made to provide insight into their commercialization. PMID- 26270232 TI - Serum levels of chemokines CCL4 and CCL5 in cirrhotic patients indicate the presence of hepatocellular carcinoma. AB - BACKGROUND: Most hepatocellular carcinomas (HCCs) are diagnosed at an advanced stage. The prognostic value of serum tumour markers alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) is limited. The aim of our study is to evaluate the diagnostic value of serum growth factors, apoptotic and inflammatory mediators of cirrhotic patients with and without HCC. METHODS: Serum samples were collected from cirrhotic potential liver transplant patients (LTx) with (n=61) and without HCC (n=78) as well as from healthy controls (HCs; n=39). Serum concentrations of CRP, neopterin and IL-6 as markers of inflammation and thrombopoietin (TPO), GCSF, FGF basic and VEGF, HMGB1, CK-18 (M65) and CK18 fragment (M30) and a panel of proinflammatory chemokines (CCL2, CCL3, CCL4, CCL5, CXCL5 and IL-8) were measured. Chi square, Fisher exact, Mann-Whitney U-tests, ROC curve analysis and forward stepwise logistic regression analyses were applied. RESULTS: Patients with HCC had higher serum TPO and chemokines (P<0.001 for TPO, CCL4, CCL5 and CXCL5) and lower CCL2 (P=0.008) levels than cirrhotic patients without HCC. Multivariate forward stepwise regression analysis for significant parameters showed that among the studied parameters CCL4 and CCL5 (P=0.001) are diagnostic markers of HCC. Serum levels of TPO and chemokines were lower, whereas M30 was significantly higher in cirrhotic patients than in HCs. CONCLUSIONS: High serum levels of inflammatory chemokines such as CCL4 and CCL5 in the serum of cirrhotic patients indicate the presence of HCC. PMID- 26270237 TI - Genome-Directed Lead Discovery: Biosynthesis, Structure Elucidation, and Biological Evaluation of Two Families of Polyene Macrolactams against Trypanosoma brucei. AB - Marine natural products are an important source of lead compounds against many pathogenic targets. Herein, we report the discovery of lobosamides A-C from a marine actinobacterium, Micromonospora sp., representing three new members of a small but growing family of bacterially produced polyene macrolactams. The lobosamides display growth inhibitory activity against the protozoan parasite Trypanosoma brucei (lobosamide A IC50 = 0.8 MUM), the causative agent of human African trypanosomiasis (HAT). The biosynthetic gene cluster of the lobosamides was sequenced and suggests a conserved cluster organization among the 26-membered macrolactams. While determination of the relative and absolute configurations of many members of this family is lacking, the absolute configurations of the lobosamides were deduced using a combination of chemical modification, detailed spectroscopic analysis, and bioinformatics. We implemented a "molecules-to-genes to-molecules" approach to determine the prevalence of similar clusters in other bacteria, which led to the discovery of two additional macrolactams, mirilactams A and B from Actinosynnema mirum. These additional analogs have allowed us to identify specific structure-activity relationships that contribute to the antitrypanosomal activity of this class. This approach illustrates the power of combining chemical analysis and genomics in the discovery and characterization of natural products as new lead compounds for neglected disease targets. PMID- 26270238 TI - Trapping Nanostructures on Surfaces through Weak Interactions. AB - The assembly of imidazole-functionalized phenanthroline-strapped zinc porphyrins (ZnPorphen) with alkyl or polyethylene glycol (PEG) side chains was studied in solution and by AFM after casting on highly oriented pyrolytic graphite (HOPG) or mica. The nature of the solvent and its evaporation time influenced the morphology of the objects observed. On HOPG, short rods of about 100 nm were observed after fast evaporation of solutions of the alkyl derivatives in CHCl3 , THF, or pyridine, whereas islands of aligned rows of longer wires were obtained from methylcyclohexane (MCH). Slow evaporation of MCH led to a three-dimensional assembly. The PEG porphyrin assembled into short wires on HOPG or fibers on mica after slow evaporation of solutions in THF. This study shows the role of surface molecule interactions in the interfacial assembly of ZnPorphen derivatives and contributes to understanding the parameters that control their noncovalent assembly into molecular wires on a surface. PMID- 26270239 TI - Nuclear Quantum Effects in the Layering and Diffusion of Hydrogen Isotopes in Carbon Nanotubes. AB - Although recent experimental studies have demonstrated that H2 and D2 molecules wet the inner surface of supergrowth carbon nanotubes at low temperatures, characterization of the structural and dynamical properties in this regime is challenging. This Letter presents a theoretical study of self-diffusion in pure and binary H2, D2, and T2 contact monolayer films formed on the inner surface of a carbon nanotube. Our results show that monolayer formation and self-diffusion both in pure hydrogen isotopes and in H2/T2 and H2/D2 isotope mixtures is impacted by nuclear quantum effects, suggesting potential applications of carbon nanotubes for the separation of hydrogen isotopes. PMID- 26270236 TI - Function and diagnostic value of Anosmin-1 in gastric cancer progression. AB - Gastric cancer (GC) is a major global health problem that urgently requires novel molecular biomarkers for patient stratification as well as therapeutic targets. Anosmin-1 (ANOS1) gene encodes a cell adhesion molecule that plays diverse roles in multiple malignancies. We performed global expression profiling of GC cell lines and small interfering RNA (siRNA) experiments to determine the effect of ANOS1 expression on phenotype. We evaluated the association of ANOS1 mRNA and protein levels in patients' tissue and sera with clinicopathological factors of GC subtypes. Differential expression of ANOS1 mRNA by GC cell lines correlated positively to levels of ITGAV, FOXC2 and NODAL mRNAs and inversely with those of TFPI2. Inhibiting ANOS1 expression decreased the proliferation, invasion and migration of GC cells. The mean level of ANOS1 mRNA was significantly higher in 237 GC tissues compared with the corresponding noncancerous adjacent tissues. Elevated ANOS1 levels associated significantly with the phenotypes of GC, shorter disease-free and overall survival. ANOS1 expression was a more significant prognostic marker for diffuse and distal nondiffuse GC. ANOS1 concentrations in sera increased sequentially in sera of healthy subjects, localized GC and disseminated GCs. Prognosis was worse for patients with preoperative serum ANOS1 >= 600 pg/ml compared with those with <600 pg/ml. ANOS1 may represent a biomarker for GC phenotypes and as a target for therapy. PMID- 26270240 TI - Acetylcholine induces fibrogenic effects via M2/M3 acetylcholine receptors in non alcoholic steatohepatitis and in primary human hepatic stellate cells. AB - BACKGROUND: The parasympathetic nervous system (PNS), via neurotransmitter acetylcholine (ACh), modulates fibrogenesis in animal models. However, the role of ACh in human hepatic fibrogenesis is unclear. AIMS: We aimed to determine the fibrogenic responses of human hepatic stellate cells (hHSC) to ACh and the relevance of the PNS in hepatic fibrosis in patients with non-alcoholic steatohepatitis (NASH). METHODS: Primary hHSC were analyzed for synthesis of endogenous ACh and acetylcholinesterase and gene expression of choline acetyltransferase and muscarinic ACh receptors (mAChR). Cell proliferation and fibrogenic markers were analyzed in hHSC exposed to ACh, atropine, mecamylamine, methoctramine, and 4-diphenylacetoxy-N-methylpiperidine methiodide. mAChR expression was analyzed in human NASH scored for fibrosis. RESULTS: We observed that hHSC synthesize ACh and acetylcholinesterase and express choline acetyltransferase and M1-M5 mAChR. We also show that M2 was increased during NASH progression, while both M2 and M3 were found upregulated in activated hHSC. Furthermore, endogenous ACh is required for hHSC basal growth. Exogenous ACh resulted in hHSC hyperproliferation via mAChR and phosphoinositide 3-kinase and Mitogen-activated protein kinase kinase (MEK) signaling pathways, as well as increased fibrogenic markers. CONCLUSION: We show that ACh regulates hHSC activation via M2 and M3 mAChR involving the phosphoinositide 3-kinase and MEK pathways in vitro. Finally, we provide evidence that the PNS may be involved in human NASH fibrosis. PMID- 26270241 TI - The aspartyl protease TgASP5 mediates the export of the Toxoplasma GRA16 and GRA24 effectors into host cells. AB - Toxoplasma gondii and Plasmodium species are obligatory intracellular parasites that export proteins into the infected cells in order to interfere with host signalling pathways, acquire nutrients or evade host defense mechanisms. With regard to export mechanism, a wealth of information in Plasmodium spp. is available, while the mechanisms operating in T. gondii remain uncertain. The recent discovery of exported proteins in T. gondii, mainly represented by dense granule resident proteins, might explain this discrepancy and offers a unique opportunity to study the export mechanism in T. gondii. Here, we report that GRA16 export is mediated by two protein elements present in its N-terminal region. Because the first element contains a putative Plasmodium export element linear motif (RRLAE), we hypothesized that GRA16 export depended on a maturation process involving protein cleavage. Using both N- and C-terminal epitope tags, we provide evidence for protein proteolysis occurring in the N-terminus of GRA16. We show that TgASP5, the T. gondii homolog of Plasmodium plasmepsin V, is essential for GRA16 export and is directly responsible for its maturation in a Plasmodium export element-dependent manner. Interestingly, TgASP5 is also involved in GRA24 export, although the GRA24 maturation mechanism is TgASP5-independent. Our data reveal different modus operandi for protein export, in which TgASP5 should play multiple functions. PMID- 26270242 TI - The Impact of Grain Alignment of the Electron Transporting Layer on the Performance of Inverted Bulk Heterojunction Solar Cells. AB - This report presents a new strategy for improving solar cell power conversion efficiencies (PCEs) through grain alignment and morphology control of the ZnO electron transport layer (ETL) prepared by radio frequency (RF) magnetron sputtering. The systematic control over the ETL's grain alignment and thickness is shown, by varying the deposition pressure and operating substrate temperature during the deposition. Notably, a high PCE of 6.9%, short circuit current density (J(sc)) of 12.8 mA cm(-2), open circuit voltage (V(oc)) of 910 mV, and fill factor of 59% are demonstrated using the poly(benzo[1,2-b:4,5-b']dithiophene thieno[3,4-c]pyrrole-4,6-dione):[6,6]-phenyl-C(71) -butyric acid methyl ester polymer blend with ETLs prepared at room temperature exhibiting oriented and aligned rod-like ZnO grains. Increasing the deposition temperature during the ZnO sputtering induces morphological cleavage of the rod-like ZnO grains and therefore reduced conductivity from 7.2 * 10(-13) to ~1.7 * 10(-14) S m(-1) and PCE from 6.9% to 4.28%. An investigation of the charge carrier dynamics by femtosecond (fs) transient absorption spectroscopy with broadband capability reveals clear evidence of faster carrier recombination for a ZnO layer deposited at higher temperature, which is consistent with the conductivity and device performance. PMID- 26270244 TI - Hydrogen-Bond Controlled pi-Dimerization in Viologen-Appended Calixarenes: Revealing a Subtle Balance of Weak Interactions. AB - The intramolecular pi-dimerization between two 4,4'-bipyridinium cation radicals directly connected to the wide rim of a calixarene is described. The ability of a phenol-containing calixarene to dimerize in its two-electron-reduced state depends on a subtle balance of weak interactions associated with hydrogen bond formation on the lower rim and orbital overlap between pi-radicals on the upper rim. PMID- 26270245 TI - Advanced Graphene-Based Binder-Free Electrodes for High-Performance Energy Storage. AB - The increasing demand for energy has triggered tremendous research effort for the development of high-performance and durable energy-storage devices. Advanced graphene-based electrodes with high electrical conductivity and ion accessibility can exhibit superior electrochemical performance in energy-storage devices. Among them, binder-free configurations can enhance the electron conductivity of the electrode, which leads to a higher capacity by avoiding the addition of non conductive and inactive binders. Graphene, a 2D material, can be fabricated into a porous and flexible structure with an interconnected conductive network. Such a conductive structure is favorable for both electron and ion transport to the entire electrode surface. In this review, the main processes used to prepare binder-free graphene-based hybrids with high porosity and well-designed electron conductive networks are summarized. Then, the applications of free-standing binder-free graphene-based electrodes in energy-storage devices are discussed. Future research aspects with regard to overcoming the technological bottlenecks are also proposed. PMID- 26270243 TI - Angiogenic characteristics of blood outgrowth endothelial cells from patients with von Willebrand disease. AB - BACKGROUND: Endothelial von Willebrand factor (VWF) inhibits angiogenesis. Accordingly, blood outgrowth endothelial cells (BOECs) isolated from von Willebrand disease (VWD) patients showed enhanced in vitro angiogenesis when compared with healthy control BOECs. Characterization of the angiogenic response of VWD BOECs is limited and differences between the different types of VWD have not been investigated in detail. OBJECTIVES: The aim of this study was to further explore the potential pathogenic effect of VWF mutations on angiogenesis. METHODS: BOECs were isolated from four healthy individuals, 10 patients with VWD and one heterozygous carrier of a type 2N mutation. Cell migration and tube formation were measured. RESULTS: Migration velocity and total tube formation were similar between VWD patients and controls in general. BOECs from the type 3 VWD patient and one type 2B patient showed increased migratory velocity and tube formation compared with BOECs from other patients and healthy controls. Directional migration was impaired in eight out of 10 VWD BOECs and the ability to form tubes was limited to early passage numbers, but not for BOECs from healthy controls. CONCLUSION: BOECs can be a useful tool for ex vivo assessment of endothelial cell function in patients with different types of VWD, but possible limitations, such as early loss of angiogenic capacity, should be recognized. BOECs from most VWD patients consistently showed impairment in the directionality of migration. This is the first report on angiogenic properties of a type 3 VWD BOEC, which showed increased in vitro angiogenesis. PMID- 26270246 TI - Phylogeographic inference using Bayesian model comparison across a fragmented chorus frog species complex. AB - Fragmented species complexes provide an interesting system for investigating biogeographic history and the present distribution of genetic variation. Recent advances in sequencing technology and statistical phylogeography enable the collection and rigorous analysis of large multilocus data sets, but designing studies that produce meaningful phylogeographic inferences remains challenging. We implemented a Bayesian model comparison approach to investigate previous biogeographic hypotheses while simultaneously inferring the presence of genetic structure in a chorus frog species complex. The Illinois chorus frog (Pseudacris illinoensis), originally described as a subspecies of the broadly distributed Strecker's chorus frog (Pseudacris streckeri), occurs in small, disjunct regions associated with scarce sand prairie habitats that have been impacted by human development. We used high-throughput sequencing to develop and collect a multitiered genetic data set comprised of three different marker types (23 anonymous nuclear sequence loci, four mitochondrial genes and 14 microsatellite loci) designed to address questions across different evolutionary timescales. Phylogenetic analyses uncovered a deep divergence between populations in the Edwards Plateau of central Texas and all other P. streckeri/P. illinoensis populations, but suggest the disjunct distribution of P. illinoensis occurred more recently. Our best-supported migration model is consistent with the hypothesis that central Texas represented a refugium from which populations expanded via multiple routes. This model also indicates that disjunct northern and southern regions of P. illinoensis should be considered genetically distinct management units. Our study provides an evolutionary context for future studies and conservation efforts in P. illinoensis and demonstrates the utility of model based approaches for phylogeographic inference. PMID- 26270247 TI - Use of the 2-chlorotrityl chloride resin for microwave-assisted solid phase peptide synthesis. AB - A fast and efficient microwave (MW)-assisted solid-phase peptide synthesis protocol using the 2-chlorotrityl chloride resin and the Fmoc/tBu methodology, has been developed. The established protocol combines the advantages of MW irradiation and the acid labile 2-chlorotrityl chloride resin. The effect of temperature during the MW irradiation, the degree of resin substitution during the coupling of the first amino acids and the rate of racemization for each amino acid were evaluated. The suggested solid phase methodology is applicable for orthogonal peptide synthesis and for the synthesis of cyclic peptides. PMID- 26270248 TI - Diameter-Selective Dispersion of Carbon Nanotubes via Polymers: A Competition between Adsorption and Bundling. AB - The mechanism of the selective dispersion of single-walled carbon nanotubes (CNTs) by polyfluorene polymers is studied in this paper. Using extensive molecular dynamics simulations, it is demonstrated that diameter selectivity is the result of a competition between bundling of CNTs and adsorption of polymers on CNT surfaces. The preference for certain diameters corresponds to local minima of the binding energy difference between these two processes. Such minima in the diameter dependence occur due to abrupt changes in the CNT's coverage with polymers, and their calculated positions are in quantitative agreement with preferred diameters reported experimentally. The presented approach defines a theoretical framework for the further understanding and improvement of dispersion/extraction processes. PMID- 26270250 TI - PROceeding With the Patient-Reported Outcomes (PROs) Version of the Common Terminology Criteria for Adverse Events. PMID- 26270249 TI - Circulating microRNAs as Potential Biomarkers of Endothelial Dysfunction in Obese Children. AB - BACKGROUND: Cardiovascular disease (CVD) is a complex disease with multifactorial etiology. The presence of endothelial dysfunction constitutes an early risk factor for CVD in children. Circulating microRNAs (miRNAs) are small noncoding RNAs that regulate gene expression and represent a novel class of biomarkers and therapeutic targets; therefore, we examined whether the presence of endothelial dysfunction is associated with differential expression of plasma miRNAs in otherwise healthy children. METHODS: A total of 70 children (aged 5-10 years) were recruited and classified into two groups (normal endothelial function [NEF] and endothelial dysfunction). Time to peak postocclusive reperfusion (Tmax) was considered as the indicator of either normal endothelial function (NEF; Tmax < 45 s) or endothelial dysfunction (Tmax >= 45 s). Lipid profiles, high-sensitivity C reactive protein, fasting glucose, and insulin were assayed using enzyme-linked immunosorbent assay. miRNAs isolated from plasma were assayed with a custom human CVD array, followed by quantitative polymerase chain reaction verification of candidates. In addition, bioinformatics approaches including combinatorial target prediction algorithms and gene ontology were applied. RESULTS: Three miRNAs that have been previously linked to cardiomyopathy, hsa-miR-125a-5p, hsa-miR-342-3p, and hsa-miR-365b-3p, were identified as potential biomarkers of children with endothelial dysfunction. The miRNA predicted gene targets revealed 31 common targets among all three putative candidate biomarker miRNAs and encompass three biologic pathways, including transforming growth factor-beta signaling, cytokine cytokine receptor interactions, and activin receptor-like kinase in cardiac myocytes. CONCLUSIONS: Plasma miRNAs may be useful as potential screening tools for the presence of endothelial dysfunction in children and may reveal endothelial dysfunction-relevant target genes. PMID- 26270251 TI - Association of compounded bevacizumab with postinjection endophthalmitis. AB - IMPORTANCE: Current draft guidelines set forth by the US Food and Drug Administration for compounded or repackaged medications would greatly limit the availability and use of bevacizumab by ophthalmologists across the country. Little evidence beyond highly publicized case reports exists for or against the need for additional regulation of compounded bevacizumab. OBJECTIVE: To determine whether the distribution of bevacizumab through compounding pharmacies increases the risk for endophthalmitis compared with the distribution of single-use vials of ranibizumab from the manufacturer. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study using medical claims data from ambulatory care centers across the United States that were submitted to a large, national US insurer. Cohorts were created using information on 530 382 intravitreal injections administered from January 1, 2005, through December 31, 2012. Any individual from this data set who received an intravitreal injection of bevacizumab or ranibizumab (n=383 810) and had at least 6 months of data before and 1 month after the injection was eligible. After exclusions (any previous diagnosis of endophthalmitis, multiple injected drugs given on the index day, or intraocular surgery within 15 days of the injection or between the injection and a diagnosis of endophthalmitis), our analysis involved 383 810 intravitreal injections given to 58 612 patients. Data collection and analysis occurred from February 16 through April 7, 2015. MAIN OUTCOMES AND MEASURES: The odds of developing endophthalmitis after an intravitreal injection of bevacizumab compared with ranibizumab. RESULTS: In total, 296 565 injections of bevacizumab were given to 51 116 patients and 87 245 injections of ranibizumab were given to 7496 patients. We found 71 cases of endophthalmitis (49 in the bevacizumab cohort and 22 in the ranibizumab cohort) for an endophthalmitis rate of 0.017% (95% CI, 0.012%-0.021%; 1 case per 6061 injections) for bevacizumab and 0.025% (95% CI, 0.015%-0.036%; 1 case per 3968 injections) for ranibizumab. After controlling for age, race, sex, injection-related diagnosis, and year of injection, we found no significant association with development of endophthalmitis after a bevacizumab injection compared with ranibizumab (odds ratio, 0.66 [95% CI, 0.39-1.09]; P = .11). CONCLUSIONS AND RELEVANCE: The results of this study suggest bevacizumab as currently used across the United States does not increase the risk for endophthalmitis; therefore, additional regulations on the use of repackaged bevacizumab may be unnecessary. PMID- 26270254 TI - Errors in Author Names. PMID- 26270255 TI - Nasal Jet-CPAP (variable flow) versus Bubble-CPAP in preterm infants with respiratory distress: an open label, randomized controlled trial. AB - OBJECTIVE: To compare the failure rates between Jet continuous positive airway pressure device (J-CPAP-variable flow) and Bubble continuous positive airway device (B-CPAP) in preterm infants with respiratory distress. STUDY DESIGN: Preterm newborns <34 weeks gestation with onset of respiratory distress within 6 h of life were randomized to receive J-CPAP (a variable flow device) or B-CPAP (continuous flow device). A standardized protocol was followed for titration, weaning and removal of CPAP. Pressure was monitored close to the nares in both the devices every 6 hours and settings were adjusted to provide desired CPAP. The primary outcome was CPAP failure rate within 72 h of life. Secondary outcomes were CPAP failure within 7 days of life, need for surfactant post-randomization, time to CPAP failure, duration of CPAP and complications of prematurity. An intention to treat analysis was done. RESULTS: One-hundred seventy neonates were randomized, 80 to J-CPAP and 90 to B-CPAP. CPAP failure rates within 72 h were similar in infants who received J-CPAP and in those who received B-CPAP (29 versus 21%; relative risks 1.4 (0.8 to 2.3), P=0.25). Mean (95% confidence intervals) time to CPAP failure was 59 h (54 to 64) in the Jet CPAP group in comparison with 65 h (62 to 68) in the Bubble CPAP group (log rank P=0.19). All other secondary outcomes were similar between the two groups. CONCLUSION: In preterm infants with respiratory distress starting within 6 h of life, CPAP failure rates were similar with Jet CPAP and Bubble CPAP. PMID- 26270257 TI - Competing Mechanisms, Substituent Effects, and Regioselectivities of Nickel Catalyzed [2 + 2 + 2] Cycloaddition between Carboryne and Alkynes: A DFT Study. AB - Competing reaction mechanisms, substituent effects, and regioselectivities of Ni(PPh3)2-catalyzed [2 + 2 + 2] carboryne-alkyne cycloadditions were characterized by density functional theory using the real chemical systems and solvent effects considered. A putative mechanism involving the following steps was characterized: (1) exothermic carboryne-catalyst complexation and nucleophilic attack by the first alkyne; (2) insertion of the second alkyne, the rate-determining step (RDS) in all four reactions studied; (3) isomerization of reactant-bound complexes; and (4) product elimination and catalyst regeneration. The RDS in three reactions is mediated by free energy barriers of 27.2, 31.1, and 36.6 kcal.mol(-1), representative of the corresponding experimental yields of 67, 54, and 33%, respectively. A fourth reaction with 0% experimental yield showed representative RDS free energy barriers of 60.4 kcal.mol(-1), which are difficult to surmount even at 90 degrees C. Alternative pathways leading to differing isomers were similarly characterized and successfully reproduced experimentally determined product regioselectivities. Kinetic data derived from free energy barriers are in quantitative agreement (< +/- 0.75-3.0 kcal.mol(-1)) of the experimental times, affirming the theoretical results as representative of the real chemical transformations. Complementary determinations show the use of truncated models (Ni(PMe3)2, Ni(PH3)2) causes the RDS to vary from step 2 (alkyne insertion) to step 1 (alkyne attack), highlighting the need to employ real chemical systems in modeling these reactions. PMID- 26270259 TI - Diastereoselective Addition of Metal alpha-Fluoroenolates of Carboxylate Esters to N-tert-Butylsulfinyl Imines: Synthesis of alpha-Fluoro-beta-amino Acids. AB - We report a diastereoselective addition reaction of fluoroacetate and alpha alkylated fluoroacetate to N-tert-butylsulfinyl imines. This method provides a concise route to alpha-fluoro-beta-amino acids containing fluorinated quaternary stereogenic carbon centers with very good yields and high diastereoselectivities. This protocol has the benefit of using abundant and readily accessible starting materials and is operationally simple. Additionally, the stereochemical outcome of the present reaction was different from that of the previously known addition of comparable nonfluorinated, brominated, and chlorinated enolates to N-sulfinyl imines, suggesting that an open transition state (rather than a closed one) is involved in the current fluoroalkylation reaction. PMID- 26270256 TI - How to manage neonatal tuberculosis. AB - This article reports the recommendations for managing neonatal tuberculosis (TB) drawn up by a group of Italian scientific societies. The Consensus Conference method was used, and relevant publications in English were identified through a systematic review of MEDLINE and the Cochrane Database of Systematic Reviews from their inception until 31 December 2014. Group experts concluded that if suspicion is aroused, it is necessary to undertake promptly all of the investigations useful for identifying the disease not only in the newborn, but also in the mother and family contacts because a diagnosis of TB in the family nucleus can guide its diagnosis and treatment in the newborn. If the suspicion is confirmed, empirical treatment should be started. Breast-fed newborns being treated with isoniazid should be given pyridoxine supplementation at a dose of 1 mg kg(-1) day(-1). Mothers with active-phase TB can breast-feed once they have become smear negative after having received appropriate treatment. PMID- 26270260 TI - Perylene Bisimide Dye Assemblies as Archetype Functional Supramolecular Materials. PMID- 26270258 TI - Nanodrug Formed by Coassembly of Dual Anticancer Drugs to Inhibit Cancer Cell Drug Resistance. AB - Carrier-free pure nanodrugs (PNDs) that are composed entirely of pharmaceutically active molecules are regarded as promising candidates to be the next generation of drug formulations and are mainly formulated from supramolecular self-assembly of drug molecules. It benefits from the efficient use of drug compounds with poor aqueous solubility and takes advantage of nanoscale drug delivery systems. Here, a type of all-in-one nanoparticle consisting of multiple drugs with enhanced synergistic antiproliferation efficiency against drug-resistant cancer cells has been created. To nanoparticulate the anticancer drugs, 10-hydroxycamptothecin (HCPT) and doxorubicin (DOX) were chosen as a typical model. The resulting HD nanoparticles (HD NPs) were formulated by a "green" and convenient self assembling method, and the water-solubility of 10-hydroxycamptothecin (HCPT) was improved 50-fold after nanosizing by coassembly with DOX. The formation process was studied by observing the morphological changes at various reaction times and molar ratios of DOX to HCPT. Molecular dynamics (MD) simulations showed that DOX molecules tend to assemble around HCPT molecules through intermolecular forces. With the advantage of nanosizing, HD NPs could improve the intracellular drug retention of DOX to as much as 2-fold in drug-resistant cancer cells (MCF-7R). As a dual-drug-loaded nanoformulation, HD NPs effectively enhanced drug cytotoxicity to drug-resistant cancer cells. The combination of HCPT and DOX exhibited a synergistic effect as the nanosized HD NPs improved drug retention in drug resistant cancer cells against P-gp efflux in MCF-7R cells. Furthermore, colony forming assays were applied to evaluate long-term inhibition of cancer cell proliferation, and these assays confirmed the greatly improved cytotoxicity of HD NPs in drug-resistant cells compared to free drugs. PMID- 26270261 TI - Paranasal Sinus Mucocele as a Late Complication of Dacryocystorhinostomy. AB - A 50-year-old female presented with a slowly enlarging painless mass of the right medial canthus. The past surgical history is significant for external dacryocystorhinostomy for acquired nasolacrimal duct obstruction 10 years prior and subsequent endoscopic and external revisions. Imaging revealed a large fronto ethmoidal sinus mucocele extending into the right medial orbit. On surgical exploration, the right middle turbinate was found to have lateralized, obstructing sinus outflow. The mucocele was evacuated and ethmoidectomy and middle turbinectomy were performed. The patient did well postoperatively without recurrence at 6 months of follow-up. Sinus mucocele formation is a rare, late complication of lacrimal surgery. PMID- 26270262 TI - Orbital Extension of Untreated Lacrimal Sac Melanoma Following Dacryocystorhinostomy. PMID- 26270263 TI - Comparative studies on biological activity of generic and branded enoxaparin in vivo and vitro. AB - As per US Food and Drug Administration (FDA) requirement, the study was designed to conduct the fourth and fifth criteria of Abbreviated New Drug Application to demonstrate equivalence of generic and branded Enoxaparin in vivo and vitro.Pharmacodynamic behavior of branded and generic Enoxaparin was compared in a parallel study in rats based upon measurement of anti-FXa and anti-FIIa profiles. Blood samples collected at baseline and at 0.5, 1, 2, 4, 6, 8, 12 and 24 h postsubcutaneous administration of six batches of Lovenox and nine batches of generic Enoxaparin were evaluated for anti-FXa and anti-FIIa using chromogenic substrate method. Anti-FXa, Anti-FIIa, activated partial thromboplastin time (APTT), and Heptest prolongation time were conducted in vitro as per the United States Pharmacopeia method. Pharmacodynamics parameters were obtained including peak effect (anti-FXamax, anti-FIIamax), area under the effect curve (AUEC0-T and AUEC0-infinity), Tmax, and T1/2.Pharmacokinetic differences were not observed using anti-FXa or anti-FIIa. No statistically significant differences were observed between branded and generic Enoxaparin either in vitro anti-FXa, anti FIIa, APTT, or Heptest assay.It can be concluded that they are bioequivalent in anticoagulant activity tested in vivo and vitro. PMID- 26270264 TI - Intraoperative Intratumoral Embolization of a Complex Recurrent Hemangiopericytoma: Technical Report and Review of the Literature. AB - Objective Recurrent brain tumors represent a challenge for neurosurgeons because of the extensive blood loss and the time needed for surgical resection. Only a few hemostatic agents are useful to prevent the bleeding and thus facilitate the surgical resection. Fibrin sealant can be used to achieve sealing, tissue adherence, or hemostasis when other means of hemostasis are inadequate or inappropriate. We report the feasibility and positive effects of direct intratumoral injection of fibrin sealant during resection of a recurrent hemangiopericytoma. Material and Methods The intraoperative intratumoral injection of fibrin sealant changed the tumor properties of a recurrent hemangiopericytoma of the tentorium with infra- and supratentorial extension. From a loose friable briskly bleeding tumor, this complex lesion became a nonbleeding well-demarcated soft-firm tumor that could easily be dissected off the pial surface and totally resected without extensive bleeding. Results There are several benefits of intratumoral injection of fibrin sealant in hemangiopericytomas: (1) the extensive bleeding is diminished and blood loss minimized; (2) the restriction of the surgical view by the venous oozing is diminished, making the microsurgical dissection of the tumor capsule off the pial surface easier and safer; (3) the loose consistency of the tumor becomes firmer and facilitates the manipulation of the tumor and leads to a safer resection; and (4) a shorter operating time is needed. Conclusion The use of intratumoral fibrin glue injection is a safe and useful technique that could be used for hemostasis of highly vascularized tumors to facilitate a safer resection and to reduce blood loss. PMID- 26270265 TI - Phosphoproteomic Analysis of Aurora Kinase Inhibition in Monopolar Cytokinesis. AB - Cytokinesis is the last step of the cell cycle that requires coordinated activities of the microtubule cytoskeleton, actin cytoskeleton, and membrane compartments. Aurora B kinase is one of the master regulatory kinases that orchestrate multiple events during cytokinesis. To reveal targets of the Aurora B kinase, we combined quantitative mass spectrometry with chemical genetics. Using the quantitative proteomic approach, SILAC (stable isotope labeling with amino acids in cell culture), we analyzed the phosphoproteome of monopolar cytokinesis upon VX680- or AZD1152-mediated aurora kinase inhibition. In total, our analysis quantified over 20 000 phosphopeptides in response to the Aurora-B kinase inhibition; 246 unique phosphopeptides were significantly down-regulated and 74 were up-regulated. Our data provide a broad analysis of downstream effectors of Aurora kinase and offer insights into how Aurora kinase regulates cytokinesis. PMID- 26270266 TI - CQC plans to test quality of NHS across whole local areas. PMID- 26270268 TI - Living Under the Constant Threat of Ebola: A Phenomenological Study of Survivors and Family Caregivers During an Ebola Outbreak. AB - BACKGROUND: Ebola is a highly infectious disease that is caused by viruses of the family Filoviridae and transmitted to humans by direct contact with animals infected from unknown natural reservoirs. Ebola virus infection induces acute fever and death within a few days in up to 90% of symptomatic individuals, causing widespread fear, panic, and antisocial behavior. Uganda is vulnerable to future Ebola outbreaks. Therefore, the survivors of Ebola and their family caregivers are likely to continue experiencing related antisocial overtones, leading to negative health outcomes. PURPOSE: This study articulated the lived experiences of survivors and their family caregivers after an Ebola outbreak in Kibale District, Western Uganda. Eliciting a deeper understanding of these devastating lifetime experiences provides opportunities for developing and implementing more compassionate and competent nursing care for affected persons. METHODS: Ebola survivors and their family caregivers were recruited using a purposive sampling method. Twelve (12) adult survivors and their family caregivers were recruited and were interviewed individually between May and July 2013 in Kibale, a rural district in Western Uganda close to the border of the Democratic Republic of the Congo, where Ebola virus was first discovered in 1976. Oral and written informed consent was obtained before all in-depth interviews, and the researchers adhered to principles of anonymity and confidentiality. The interviews were recorded digitally, and data analysis employed Wertz's Empirical Psychological Reflection method, which is grounded in descriptive phenomenology. RESULTS: Living under the constant threat of Ebola is experienced through two main categories: (a) defining features of the experience and (b) responding to the traumatizing experience. Five themes emerged in the first category: (a) fear, ostracism, and stigmatization; (b) annihilation of sufferer's actualities and possibilities; (c) the lingering nature of the traumatic experience; (d) psychosomatic manifestations; and (e) the inescapable nature of the experience. The second category was composed of two themes: (a) seeking self-preservation and protection and (b) transcending victimhood and becoming empowered. CONCLUSIONS: Living under the constant threat of Ebola is experienced as distressing in the physical, social, and psychological realms. In the future, prompt treatment and nursing care are recommended to minimize deaths and to reduce the widespread terror, anxiety, ostracism, and stigmatization that affected individuals and families face. Furthermore, it is recommended that the resilience of survivors and caregivers be increased to facilitate their better coping with the rampant antisocial overtones that they are likely to experience because of their association with Ebola. PMID- 26270269 TI - Effects of Reproductive Health Education on Knowledge and Attitudes Among Female Adolescents in Saudi Arabia. AB - BACKGROUND: For many girls, the onset of puberty that occurs during adolescence marks a time of heightened vulnerability to early pregnancy, with its attendant complications and heightened risk of maternal mortality. National and international forums have recognized the need to address these problems through reproductive health education. PURPOSE: This article assesses the reproductive health-related knowledge and attitudes of female adolescents aged between 14 and 19 years. In addition, the authors assess the effectiveness of a reproductive health education program in improving the related knowledge of female adolescents. METHODS: The study was conducted on female students in three secondary schools and in the preparatory year at Qassim University (N = 309). A 59-item structured questionnaire was used to test the knowledge and attitudes of all participants regarding reproductive health before and after the intervention program. Data collection was carried out between September and November 2012. RESULTS: A significant increase for the total sample in knowledge regarding puberty and menstruation was observed (p < .001) postintervention. Differences in overall knowledge regarding pregnancy and antenatal care were statistically significant. Knowledge regarding contraceptive intrauterine devices improved from 27.2% preintervention to 67.6% postintervention. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This study clearly showed that the reproductive health education program improves knowledge among adolescent girls regarding reproductive health. PMID- 26270271 TI - Corrigendum. PMID- 26270270 TI - Modulation of Energy Transfer into Sequential Electron Transfer upon Axial Coordination of Tetrathiafulvalene in an Aluminum(III) Porphyrin-Free-Base Porphyrin Dyad. AB - Axially assembled aluminum(III) porphyrin based dyads and triads have been constructed to investigate the factors that govern the energy and electron transfer processes in a perpendicular direction to the porphyrin plane. In the aluminum(III) porphyrin-free-base porphyrin (AlPor-Ph-H2Por) dyad, the AlPor occupies the basal plane, while the free-base porphyrin (H2Por) with electron withdrawing groups resides in the axial position through a benzoate spacer. The NMR, UV-visible absorption, and steady-state fluorescence studies confirm that the coordination of pyridine appended tetrathiafulvalene (TTF) derivative (TTF-py or TTF-Ph-py) to the dyad in noncoordinating solvents afford vertically arranged supramolecular self-assembled triads (TTF-py->AlPor-Ph-H2Por and TTF-Ph-py->AlPor Ph-H2Por). Time-resolved studies revealed that the AlPor in dyad and triads undergoes photoinduced energy and/or electron transfer processes. Interestingly, the energy and electron donating/accepting nature of AlPor can be modulated by changing the solvent polarity or by stimulating a new competing process using a TTF molecule. In modest polar solvents (dichloromethane and o-dichlorobenzene), excitation of AlPor leads singlet-singlet energy transfer from the excited singlet state of AlPor ((1)AlPor*) to H2Por with a moderate rate constant (k(EnT)) of 1.78 * 10(8) s(-1). In contrast, excitation of AlPor in the triad results in ultrafast electron transfer from TTF to (1)AlPor* with a rate constant (k(ET)) of 8.33 * 10(9)-1.25 * 10(10) s(-1), which outcompetes the energy transfer from (1)AlPor* to H2Por and yields the primary radical pair TTF(+*) AlPor(-*)-H2Por. A subsequent electron shift to H2Por generates a spatially well separated TTF(+*)-AlPor-H2Por(-*) radical pair. PMID- 26270267 TI - High frequency of central memory regulatory T cells allows detection of liver recipients at risk of early acute rejection within the first month after transplantation. AB - Several studies have analyzed the potential of T regulatory cells (Treg cells) as biomarkers of acute rejection (AR). The aim of the present multicenter study was to correlate the percentage of peripheral Treg cells in liver graft recipients drawn at baseline up to 12 months after transplantation with the presence of AR. The percentage of central memory (cm) Treg cells (CD4(+)CD25(high)CD45RO(+)CD62L(+)) was monitored at pre-transplant and at 1 and 2 weeks, and 1, 2, 3 and 6 months and 1 year post-transplantation. The same validation standard operating procedures were used in all participating centers. Fifteen patients developed AR (23.4%). Hepatitis C virus recurrence was observed in 16 recipients, who displayed low peripheral blood cmTreg levels compared with patients who did not. A steady increase of cmTregs was observed during the first month after transplantation with statistically significant differences between AR and non-AR patients. The high frequency of memory Treg cells allowed us to monitor rejection episodes during the first month post-transplantation. On the basis of these data, we developed a prediction model for assessing risk of AR that can provide clinicians with useful information for managing patients individually and customizing immunosuppressive therapies. PMID- 26270272 TI - Longitudinal, reciprocal effects of social skills and achievement from kindergarten to eighth grade. AB - Previous research suggests that students' social skills and achievement are interrelated, and some findings support bi-directional effects between the two constructs. The purpose of this research study was to estimate the possible longitudinal and reciprocal effects of social skills and achievement for kindergarten through eighth grade students. Data from the Early Childhood Longitudinal Study program were analyzed; teachers' ratings of students' social skills and students' standardized math and reading achievement performance were collected 4 and 5 times, respectively. Latent variable structural equation modeling was used to test a panel model of reciprocal, longitudinal effects of social skills and achievement. The results suggest that the effects of students' social skills and achievement are bi-directional, but the effects of students' achievement on their later social skills are stronger than the effects of social skills on achievement. The significant effects of students' social skills on their later achievement are mostly indirect. These findings suggest that the future social skills of students who struggle academically may be of particular concern to educators, and intervention and prevention efforts aimed to address both social and achievement skills may help remediate the other skill in the future. PMID- 26270274 TI - Bullying victimization and the social and emotional maladjustment of bystanders: A propensity score analysis. AB - This study investigated how bystanders, who have and have not been bullied, perceive their social and emotional maladjustment depending on the form of bullying (physical or verbal) they witness. Using propensity score matching, equivalent groups of 270 victimized and 270 non-victimized bystander groups were created based on middle school students' responses on the Bully Survey-Student Version (BYS-S; Swearer, 2001). Victimized bystanders experienced higher social maladjustment than non-victimized bystanders. Path analysis results suggest that social and emotional maladjustment as a bystander is related not only to social emotional maladjustment as victim, but to gender and the form of bullying witnessed. The way in which bystanders are influenced by their personal victimization may be a critical factor in predicting, understanding, and increasing active bystander intervention. PMID- 26270273 TI - High self-control protects the link between social support and positivity ratio for Israeli students exposed to contextual risk. AB - This study examined how Israeli students, despite exposure to contextual risk factors, may experience a high ratio of self-reported positive to negative emotions (i.e., positivity ratio). Self-control skills and perceived social support were tested as protective factors, where each was posited to moderate the relation between risk status and positivity ratio. The participants were 460 Israeli students (51% girls) in grades 8-10. Contrary to expectations, students attending a school with high contextual risks did not differ from students attending a school with low contextual risks in their scores on self-control skills, perceived social support, or positivity ratio. However, an exploratory follow-up moderation analysis revealed a significant three-way interaction, indicating that while low self-control skills eliminate the link between social support and positivity ratio for students attending the school defined as at risk, high self-control protects this link. These results suggest that neither contextual risk in itself nor initial differences in self-control or social support account for differences in students' positivity ratio. Rather, it is the way these factors interact with each other that matters. Study limitations and implications are discussed. PMID- 26270275 TI - Peer and self-reported victimization: Do non-victimized students give victimization nominations to classmates who are self-reported victims? AB - Using data from 2413 Dutch first-year secondary school students (M age=13.27, SD age=0.51, 49.0% boys), this study investigated as to what extent students who according to their self-reports had not been victimized (referred to as reporters) gave victimization nominations to classmates who according to their self-reports had been victimized (referred to as receivers). Using a dyadic approach, characteristics of the reporter-receiver dyad (i.e., gender similarity) and of the reporter (i.e., reporters' behavior during bullying episodes) that were possibly associated with reporter-receiver agreement were investigated. Descriptive analyses suggested that numerous students who were self-reported victims were not perceived as victimized by their non-victimized classmates. Three-level logistic regression models (reporter-receiver dyads nested in reporters within classrooms) demonstrated greater reporter-receiver agreement in same-gender dyads, especially when the reporter and the receiver were boys. Furthermore, reporters who behaved as outsiders during bullying episodes (i.e., reporters who actively shied away from the bullying) were less likely to agree on the receiver's self-reported victimization, and in contrast, reporters who behaved as defenders (i.e., reporters who helped and supported victims) were more likely to agree on the victimization. Moreover, the results demonstrated that reporters gave fewer victimization nominations to receivers who reported they had been victimized sometimes than to receivers who reported they had been victimized often/very often. Finally, this study suggested that reporter-receiver agreement may not only depend on characteristics of the reporter-receiver dyad and of the reporter, but on classroom characteristics as well (e.g., the number of students in the classroom). PMID- 26270276 TI - The stability of elementary school contexts from kindergarten to third grade. AB - The nature and measurement of school contexts have been the foci of interest in community, developmental, and school psychology for decades. In this paper, we tested the stability of six elementary school-context factors over time, using a nationally representative and longitudinal sample of schools from the Early Childhood Longitudinal Study, Kindergarten Class of 1998-1999 (ECLS-K), and systems theories as a conceptual framework. Confirmatory factor analyses and tests of measurement equivalence revealed that six latent factors fit the data equally well across kindergarten, first grade, and third grade: school strain, school safety practices, school academic performance, school instructional resources, positive school climate, and school violence and crime. The factors were highly stable across the early elementary school years, with standardized stability coefficients ranging from .87 to .99 between kindergarten and first grade and from .71 to .98 between the first and third grades. Equivalence in the two sets of stability coefficients was also found across time. Both the magnitude and equivalence of the stability coefficients were robust to the inclusion of five key exogenous school characteristics as covariates in the model. Results suggest that elementary school contexts are remarkably stable over time and shed light on methodological considerations regarding the treatment of school-level measures in analyses that examine links between school context and children's academic and developmental trajectories. PMID- 26270277 TI - The Impact of Inpatient Palliative Care Consultations on 30-Day Hospital Readmissions. AB - BACKGROUND: Inpatient palliative care consultations have been shown to reduce acute care utilization by reducing length of stay, but less is known about their impact on subsequent costs including hospital readmissions. OBJECTIVE: The study's objective was to examine the impact of inpatient palliative care consultations on 30-day hospital readmissions to a large urban academic medical center. METHODS: The hospital's electronic medical record system was used to identify all live discharges between August 2013 and November 2014. After adjusting for a propensity score, readmission rates were compared between palliative care and usual care groups. RESULTS: Of the 34,541 hospitalizations included in the study, 1430 (4.1%) involved a palliative care consult. After adjusting for the propensity score, patients seen by palliative care had a lower 30-day readmission rate-adjusted odds ratio (AOR) 0.66, 0.55-0.78; p<0.001. Adjusted rates were 10.3% (95% confidence interval [CI] 8.9%-12.0%) for palliative care and 15.0% (95% CI 14.4%-15.4%) for usual care. Among all palliative care patients, consultations that involved goals of care discussions were associated with a lower readmission rate (AOR 0.36, 0.27-0.48; p<0.001), but consultations involving symptom management were not (AOR 1.05, 0.82-1.35; p=0.684). CONCLUSIONS: Palliative care palliative care consultations facilitate goals discussions, which in turn are associated with reduced rates of 30-day readmissions. PMID- 26270278 TI - Platelet counts in autosomal dominant polycystic kidney disease. AB - Platelet counts in patients with autosomal dominant polycystic kidney disease (ADPKD) have been reported to be lower than in control populations in one small study but data are sparse. We retrospectively audited real world platelet data from 290 ADPKD patients with corresponding age and sex-matched controls. We analysed 42,972 individual blood counts and patients with ADPKD had statistically lower platelet counts (213 +/- 63 vs. 238 +/- 69 * 10(9)/L, p < 0.01) on dialysis. In the transplant and chronic kidney disease (CKD) groups, there were no significant differences in the platelet counts. The magnitude of the difference in platelet numbers was small and unlikely to be clinically significant, so findings of low platelets in ADPKD should be further investigated. PMID- 26270279 TI - Misinterpretation of SNAP Participation, Diet, and Weight in Low-Income Adults. PMID- 26270280 TI - "What Is Our Story?" Philip Morris's Changing Corporate Narrative. AB - OBJECTIVES: We sought to learn how employees reacted to changes in the corporate narrative of Philip Morris Companies (PMC) in the late 1990s and early 2000s. METHODS: We analyzed archival internal tobacco industry documents about PMC's creation of a new corporate story. RESULTS: In response to litigation and public opprobrium, PMC replaced its market success-oriented corporate narrative with a new one centered on responsibility. Although management sought to downplay inconsistencies between the old and new narratives, some employees reportedly had difficulty reconciling them, concerned that the responsibility focus might affect company profitability. However, others embraced the new narrative, suggesting radical ideas to prevent youth smoking. These ideas were not adopted. CONCLUSIONS: PMC's new narrative was unconvincing to many of its employees, who perceived it either as a threat to the company's continued profits or as incongruous with what they had previously been told. As it had done with the public, PMC misled its employees in explaining a narrative repositioning that would help the company continue business as usual. Moving toward a tobacco endgame will require ongoing discursive and symbolic efforts to disrupt this narrative. PMID- 26270282 TI - Organizing With Communities to Benefit Public Health. PMID- 26270281 TI - Drawing the Curtain Back on Injured Commercial Bicyclists. AB - OBJECTIVES: We determined the demographic characteristics, behaviors, injuries, and outcomes of commercial bicyclists who were injured while navigating New York City's (NYC's) central business district. METHODS: Our study involved a secondary analysis of prospectively collected data from a level 1 regional trauma center in 2008 to 2014 of bicyclists struck by motor vehicles. We performed univariable and multivariable logistic regression analyses. RESULTS: Of 819 injured bicyclists, 284 (34.7%) were working. Commercial bicyclists included 24.4% to 45.1% of injured bicyclists annually. Injured commercial bicyclists were more likely Latino (56.7%; 95% confidence interval [CI] = 50.7, 62.8 vs 22.7%; 95% CI = 19.2, 26.5). Commercial bicyclists were less likely to be distracted by electronic devices (5.0%; 95% CI = 2.7, 8.2 vs 12.7%; 95% CI = 9.9, 15.9) or to have consumed alcohol (0.7%; 95% CI = 0.9, 2.5 vs 9.5%; 95% CI = 7.2, 12.3). Commercial and noncommercial bicyclists did not differ in helmet use (38.4%; 95% CI = 32.7, 44.4 vs 30.8%; 95% CI = 26.9, 34.9). Injury severity scores were less severe in commercial bicyclists (odds ratio = 0.412; 95% CI = 0.235, 0.723). CONCLUSIONS: Commercial bicyclists represent a unique cohort of vulnerable roadway users. In NYC, minorities, especially Latinos, should be targeted for safety education programs. PMID- 26270283 TI - A Systems Approach to Improving Tdap Immunization Within 5 Community-Based Family Practice Settings: Working Differently (and Better) by Transforming the Structure and Process of Care. AB - OBJECTIVES: We examined how family medicine clinic physicians and staff worked in collaborative teams to implement an automated clinical reminder to improve tetanus, diphtheria, and acellular pertussis (Tdap) booster vaccine administration and documentation. METHODS: A clinical reminder was developed at 5 University of Michigan family medicine clinics to identify patients 11 to 64 years old who were in need of the Tdap booster vaccine. Quality improvement cycles were used to improve clinic care processes. Immunization rates from 2008 to 2011 were compared with rates at 4 primary care control clinics. RESULTS: Vaccination rates among eligible patients increased from 15.5% to 47.3% within the family medicine clinics and from 14.1% to 30.2% within the control clinics. After adjustment for covariates, family medicine patients had a higher probability of vaccination than control patients during each measurement period (0.17 vs 0.15 at baseline, 0.53 vs 0.22 during year 1, and 0.50 vs 0.30 during year 2). CONCLUSIONS: Automated clinical reminders, when designed and implemented via a consensus-based framework that addresses the process of care, can dramatically improve provision of preventive health care. PMID- 26270284 TI - Demographic and Psychosocial Factors Associated With Psychological Distress and Resilience Among Transgender Individuals. AB - OBJECTIVES: We examined the independent demographic and psychosocial factors associated with psychological distress and resilience among transgender men and women. METHODS: Our data came from an online survey involving a national Australian sample of 169 transgender men and women in 2011. Survey questions assessed demographics; sources of support; contact with lesbian, gay, bisexual, and transgender peers; and experiences of victimization. We assessed the outcomes with the Kessler Psychological Distress Scale and the Brief Resilience Scale. RESULTS: In all, 46.0% of the sample reported high or very high levels of psychological distress. Multivariable regression analyses identified considerably different independent factors for psychological distress and resilience. Younger age, feeling unable to turn to family for support, and victimization experiences were associated with greater psychological distress, whereas higher income, identifying as heterosexual, and having frequent contact with lesbian, gay, bisexual, and transgender peers were associated with greater resilience. CONCLUSIONS: With different factors identified for psychological distress and resilience, these findings may help inform the development of tailored mental health interventions and resilience-building programs for this vulnerable population. PMID- 26270285 TI - Smoking Norms and the Regulation of E-Cigarettes. AB - Electronic nicotine delivery systems (ENDS)-commonly called e-cigarettes-are at the center of a polarized debate. How should they be regulated? Central to this debate is the concern that e-cigarettes could lead to the renormalization of smoking and that the regulation of ENDS should therefore be modeled on the regulation of conventional cigarettes. I argue that arguments based on the renormalization of smoking can lend support to restrictions on marketing of ENDS, but that such arguments are problematic when used to justify restrictions on where ENDS can be used. The debate has been insufficiently sensitive to the ethical complexities of attempts to manipulate social norms to change health behaviors; these complexities must also inform the debate about ENDS and their regulation. PMID- 26270286 TI - Purtle and Roman Respond. PMID- 26270287 TI - Community Health Worker Home Visits for Medicaid-Enrolled Children With Asthma: Effects on Asthma Outcomes and Costs. AB - OBJECTIVES: We sought to estimate the return on investment of a streamlined version of an evidence-based community health worker (CHW) asthma home visit program. METHODS: We used a randomized parallel group trial of home visits by CHWs to Medicaid-enrolled children with uncontrolled asthma versus usual care. RESULTS: A total of 373 participants enrolled in the study (182 in the intervention group and 191 in the control group, of whom 154 and 179, respectively, completed the study). The intervention group had greater improvements in asthma symptom-free days (2.10 days more over 2 weeks; 95% CI = 1.17, 3.05; P < .001) and caretakers' quality of life (0.43 units more; 95% CI = 0.20, 0.66; P < .001) and a larger reduction in urgent health care utilization events (1.31 events fewer over 12 months; 95% CI = -2.10, -0.52; P = .001). The intervention arm compared with the control arm saved $1340.92 for the $707.04 additional costs invested for the average participant. The return on investment was 1.90. CONCLUSIONS: A streamlined CHW asthma home visit program for children with uncontrolled asthma improved health outcomes and yielded a return on investment of 1.90. PMID- 26270288 TI - Sexual Minority Health Disparities in Adult Men and Women in the United States: National Health and Nutrition Examination Survey, 2001-2010. AB - OBJECTIVES: We used nationally representative data to investigate health disparities associated with sexual minority status among adults in the United States. METHODS: We analyzed data from 11,114 adults who participated in the 2001 to 2010 waves of the National Health and Nutrition Examination Survey. Using multiple logistic regressions, we examined the prevalence of HIV, sexually transmitted infections, mental health problems, cigarette smoking, and alcohol and illicit drug use in sexual minorities and heterosexual adults. RESULTS: After adjusting for sociodemographic characteristics, sexual minority men had greater odds of mental health problems, testing positive for HIV and herpes simplex virus type 2 and self-reported gonorrhea and chlamydia. Sexual minority women had greater odds of mental health problems, testing positive for hepatitis C, smoking, heavy drinking, and illicit drug use. CONCLUSIONS: Numerous health disparities continue to face sexual minority men and women in the United States. Notably, health disparities persisted beyond the role of sociodemographic factors, including access to insurance and primary care, suggesting that further research is warranted to identify the determinants of health inequity for sexual minorities. PMID- 26270289 TI - The Relationship Between Financial Distress and Life-Course Socioeconomic Inequalities in Well-Being: Cross-National Analysis of European Welfare States. AB - OBJECTIVES: We investigated to what extent current financial distress explains the relationship between life-course socioeconomic position and well-being in Southern, Scandinavian, Postcommunist, and Bismarckian welfare regimes. METHODS: We analyzed individuals (n = 18 324) aged 50 to 75 years in the Survey of Health, Ageing, and Retirement in Europe, 2006-2009. Well-being was measured with CASP-12 (which stands for control, autonomy, self-realization, and pleasure) and life satisfaction. We generated a life-course socioeconomic index from 8 variables and calculated multilevel regression models (containing individuals nested within 13 countries), as well as stratified single-level models by welfare regime. RESULTS: Life-course socioeconomic advantage was related to higher well-being; the difference in life satisfaction between the most and least advantaged was 2.09 (95% confidence interval = 1.87, 2.31) among women and 1.65 (95% confidence interval = 1.43, 1.87) among men. The weakest associations were found among Scandinavian countries. Financial distress was associated with lower well-being and attenuated the relationship between life-course socioeconomic position and well-being in all regimes (ranging from 34.26% in Postcommunist to 72.22% in Scandinavian countries). CONCLUSIONS: We found narrower inequalities in well being in the Scandinavian regime. Reducing financial distress may help improve well-being and reduce inequalities. PMID- 26270290 TI - Addressing Structural and Environmental Factors for Adolescent Sexual and Reproductive Health in Low- and Middle-Income Countries. AB - A deeper understanding of how structure and environment shape the sexual and reproductive health vulnerabilities of youths across a range of outcomes has implications for the development of successful policies and programs. We have discussed some of the key structural and environmental factors that influence the sexual and reproductive health of adolescents, particularly in low- and middle income countries, and the importance of engaging adolescents in identifying solutions. We have highlighted 2 case studies that describe structural or environmental approaches to improving adolescent sexual and reproductive health and made recommendations to more systematically incorporate attention to structure and environment to improve global adolescent health. PMID- 26270291 TI - "We'll Get to You When We Get to You": Exploring Potential Contributions of Health Care Staff Behaviors to Patient Perceptions of Discrimination and Satisfaction. AB - OBJECTIVES: We qualitatively assessed patients' perceptions of discrimination and patient satisfaction in the health care setting specific to interactions with nonphysician health care staff. METHODS: We conducted 12 focus-group interviews with African American and European American participants, stratified by race and gender, from June to November 2008. We used a topic guide to facilitate discussion and identify factors contributing to perceived discrimination and analyzed transcripts for relevant themes using a codebook. RESULTS: We enrolled 92 participants: 55 African Americans and 37 European Americans, all of whom reported perceived discrimination and lower patient satisfaction as a result of interactions with nonphysician health care staff. Perceived discrimination was associated with 2 main characteristics: insurance or socioeconomic status and race. Both verbal and nonverbal communication style on the part of nonphysician health care staff were related to individuals' perceptions of how they were treated. CONCLUSIONS: The behaviors of nonphysician health care staff in the clinical setting can potentially contribute to patients' perceptions of discrimination and lowered patient satisfaction. Future interventions to reduce health care discrimination should include a focus on staff cultural competence and customer service skills. PMID- 26270293 TI - Health Care Costs 1 Year After Pediatric Traumatic Brain Injury. AB - OBJECTIVES: This study sought to estimate total health care costs for mild, moderate, and severe pediatric traumatic brain injury (TBI) and to compare individual- and population-level costs across levels of TBI severity. METHODS: Using 2007 to 2010 MarketScan Commercial Claims and Encounters data, we estimated total quarterly health care costs 1 year after TBI among enrollees (aged < 18 years). We compared costs across levels of TBI severity using generalized linear models. RESULTS: Mild TBI accounted for 96.6% of the 319 103 enrollees with TBI; moderate and severe TBI accounted for 1.7% and 1.6%, respectively. Adjusted individual health care costs for moderate and severe TBI were significantly higher than mild TBI in the year after injury (P < .01). At the population level, moderate and severe TBI costs were 88% and 75% less than mild TBI, respectively. CONCLUSIONS: Individually, moderate and severe TBI initially generated costs that were markedly higher than those of mild TBI. At the population level, costs following mild TBI far exceeded those of more severe cases, a result of the extremely high population burden of mild TBI. PMID- 26270292 TI - Indicated Prevention of Childhood Anxiety and Depression: Results From a Practice Based Study up to 12 Months After Intervention. AB - OBJECTIVES: We investigated whether intervention effects of FRIENDS for Life, a school-based prevention program for children with anxiety or depression symptoms, were maintained over a period of 12 months after the intervention in a naturalistic setting. METHODS: We used a quasi-experimental design, with 339 children in the intervention group and 157 in the control group (aged 8-13 years) in schools in Amsterdam, the Netherlands. We collected self-, teacher, and peer reports of anxiety and depression scores before and after intervention, and 6 and 12 months after intervention, from 2010 to 2012. RESULTS: Intervention-group children reported a continuing and significant decrease in anxiety and depression scores compared with the control group. Twelve months after the intervention, participants' anxiety and depression levels were comparable to those of the general population. Girls reported a stronger decrease in anxiety scores than did boys. Teacher reports suggested no effects. Although classmates reported increased internalizing problems in intervention-group children immediately after intervention, these effects disappeared over time. CONCLUSIONS: FRIENDS for Life, an indicated prevention program, yielded long-lasting and continuing reduction in anxiety and depression problems when implemented in daily school practice. PMID- 26270295 TI - The Rationalization of Unethical Research: Revisionist Accounts of the Tuskegee Syphilis Study and the New Zealand "Unfortunate Experiment". AB - Two studies, widely condemned in the 1970s and 1980s-the Tuskegee study of men with untreated syphilis and the New Zealand study of women with untreated carcinoma in situ of the cervix-received new defenses in the 21st century. We noted remarkable similarities in both the studies and their defenses. Here we evaluate the scientific, political, and moral claims of the defenders. The scientific claims are largely based on incomplete or misinterpreted evidence and exaggeration of the uncertainties of science. The defenders' political arguments mistakenly claim that identity politics clouded the original critiques; in fact such politics opened the eyes of the public to exploitation. The moral defenses demonstrate an overreliance on codes of conduct and have implications for research ethics today. PMID- 26270294 TI - Self-Reported Health Among Recently Incarcerated Mothers. AB - OBJECTIVES: We examined self-reported health among formerly incarcerated mothers. METHODS: We used data from the Fragile Families and Child Wellbeing Study (n = 4096), a longitudinal survey of mostly unmarried parents in urban areas, to estimate the association between recent incarceration (measured as any incarceration in the past 4 years) and 5 self-reported health conditions (depression, illicit drug use, heavy drinking, fair or poor health, and health limitations), net of covariates including health before incarceration. RESULTS: In adjusted logistic regression models, recently incarcerated mothers, compared with their counterparts, have an increased likelihood of depression (odds ratio [OR] = 1.60; 95% confidence interval [CI] = 1.18, 2.17), heavy drinking (OR = 1.79; 95% CI = 1.19, 2.68), fair or poor health (OR = 1.49; 95% CI = 1.08, 2.06), and health limitations (OR = 1.78; 95% CI = 1.27, 2.50). This association is similar across racial/ethnic subgroups and is larger among mothers who share children with fathers who have not been recently incarcerated. CONCLUSIONS: Recently incarcerated mothers struggle with even more health conditions than expected given the disadvantages they experience before incarceration. Furthermore, because incarceration is concentrated among those who are most disadvantaged, incarceration may increase inequalities in population health. PMID- 26270296 TI - Public Health in the Unrest: Baltimore's Preparedness and Response After Freddie Gray's Death. PMID- 26270297 TI - E-cigarettes May Impair Ability to Quit, but Other Explanations Are Possible. PMID- 26270299 TI - Flu Near You: Crowdsourced Symptom Reporting Spanning 2 Influenza Seasons. AB - OBJECTIVES: We summarized Flu Near You (FNY) data from the 2012-2013 and 2013 2014 influenza seasons in the United States. METHODS: FNY collects limited demographic characteristic information upon registration, and prompts users each Monday to report symptoms of influenza-like illness (ILI) experienced during the previous week. We calculated the descriptive statistics and rates of ILI for the 2012-2013 and 2013-2014 seasons. We compared raw and noise-filtered ILI rates with ILI rates from the Centers for Disease Control and Prevention ILINet surveillance system. RESULTS: More than 61 000 participants submitted at least 1 report during the 2012-2013 season, totaling 327 773 reports. Nearly 40 000 participants submitted at least 1 report during the 2013-2014 season, totaling 336 933 reports. Rates of ILI as reported by FNY tracked closely with ILINet in both timing and magnitude. CONCLUSIONS: With increased participation, FNY has the potential to serve as a viable complement to existing outpatient, hospital-based, and laboratory surveillance systems. Although many established systems have the benefits of specificity and credibility, participatory systems offer advantages in the areas of speed, sensitivity, and scalability. PMID- 26270298 TI - How Stigma Surrounding the Use of HIV Preexposure Prophylaxis Undermines Prevention and Pleasure: A Call to Destigmatize "Truvada Whores". AB - Antiretroviral preexposure prophylaxis (PrEP; emtricitabine and tenofovir disoproxil fumarate [Truvada]) prevents HIV without penalizing sexual pleasure, and may even enhance pleasure (e.g., by reducing HIV-related anxiety). However, concern about sexual risk behavior increasing with PrEP use (risk compensation) and corresponding stereotypes of promiscuity may undermine PrEP's preventive potential. In this commentary, we review literature on sexual behavior change accompanying PrEP use, discuss risk compensation concerns and the "Truvada whore" stereotype as PrEP barriers, question the appropriateness of restricting PrEP access because of risk compensation, and consider sexual pleasure as a benefit of PrEP, an acceptable motive for seeking PrEP, and a core element of health. It is essential for science to trump stereotypes and sex-negative messaging in guiding decision-making affecting PrEP access and uptake. PMID- 26270302 TI - Regarding Health Awareness Days. PMID- 26270301 TI - The Contribution of Missed Clinic Visits to Disparities in HIV Viral Load Outcomes. AB - OBJECTIVES: We explored the contribution of missed primary HIV care visits ("no show") to observed disparities in virological failure (VF) among Black persons and persons with injection drug use (IDU) history. METHODS: We used patient-level data from 6 academic clinics, before the Centers for Disease Control and Prevention and Health Resources and Services Administration Retention in Care intervention. We employed staged multivariable logistic regression and multivariable models stratified by no-show visit frequency to evaluate the association of sociodemographic factors with VF. We used multiple imputations to assign missing viral load values. RESULTS: Among 10 053 patients (mean age = 46 years; 35% female; 64% Black; 15% with IDU history), 31% experienced VF. Although Black patients and patients with IDU history were significantly more likely to experience VF in initial analyses, race and IDU parameter estimates were attenuated after sequential addition of no-show frequency. In stratified models, race and IDU were not statistically significantly associated with VF at any no show level. CONCLUSIONS: Because missed clinic visits contributed to observed differences in viral load outcomes among Black and IDU patients, achieving an improved understanding of differential visit attendance is imperative to reducing disparities in HIV. PMID- 26270300 TI - Discrimination and Cumulative Disease Damage Among African American Women With Systemic Lupus Erythematosus. AB - OBJECTIVES: We examined associations between unfair treatment, attributions of unfair treatment to racial discrimination, and cumulative disease damage among African American women with systemic lupus erythematosus (SLE). METHODS: We used multivariable regression models to examine SLE damage among 578 African American women in metropolitan Atlanta, Georgia, recruited to the Georgians Organized Against Lupus cohort. RESULTS: When we controlled for demographic, socioeconomic, and health-related covariates, reporting any unfair treatment was associated with greater SLE damage compared with reporting no unfair treatment (b = 0.55; 95% confidence interval = 0.14, 0.97). In general, unfair treatment attributed to nonracial factors was more strongly associated with SLE damage than was unfair treatment attributed to racial discrimination, although the difference was not statistically significant. CONCLUSIONS: Unfair treatment may contribute to worse disease outcomes among African American women with SLE. Unfair treatment attributed to nonracial causes may have a more pronounced negative effect on SLE damage. Future research may further examine possible differences in the effect of unfair treatment by attribution. PMID- 26270304 TI - Profiles of Food Security for US Farmworker Households and Factors Related to Dynamic of Change. AB - OBJECTIVES: We recruited 248 farmworker families with preschool-aged children in North Carolina and examined food security indicators over 24 months to identify food security patterns and examine the dynamic of change over time. METHODS: Participants in the Ninos Sanos study, conducted 2011 to 2014, completed quarterly food security assessments. Based on responses to items in the US Household Food Security Survey Module, we identified different states of food security by using hidden Markov model analysis, and examined factors associated with different states. We delineated factors associated with changes in state by using mixed-effect ordinal logistic regression. RESULTS: About half of the households (51%) consistently stayed in the most food-secure state. The least food-secure state was transient, with only 29% probability of this state for 2 consecutive quarters. Seasonal (vs migrant) work status, having immigration documents (vs not documented), and season predicted higher levels of food security. CONCLUSIONS: Heterogeneity in food security among farmworker households calls for tailoring intervention strategies. The transiency and unpredictability of low food security suggest that access to safety-net programs could reduce low food security risk in this population. PMID- 26270303 TI - Public Support for Family Smoking Prevention and Tobacco Control Act Point-of Sale Provisions: Results of a National Study. AB - OBJECTIVES: We assessed public and smoker support for enacted and potential point of-sale (POS) tobacco-control policies under the Family Smoking Prevention and Tobacco Control Act. METHODS: We surveyed a US nationally representative sample of 17, 507 respondents (6595 smokers) in January through February 2013, and used linear regression to calculate weighted point estimates and identify factors associated with support for POS policies among adults and smokers. RESULTS: Overall, nonsmokers were more supportive than were smokers. Regardless of smoking status, African Americans, Hispanics, women, and those of older ages were more supportive than White, male, and younger respondents, respectively. Policy support varied by provision. More than 80% of respondents supported minors' access restrictions and more than 45% supported graphic warnings. Support was lowest for plain packaging (23%), black-and-white advertising (26%), and a ban on menthol cigarettes (36%). CONCLUSIONS: Public support for marketing and POS provisions is low relative to other areas of tobacco control. Tobacco-control advocates and the Food and Drug Administration should build on existing levels of public support to promote and maintain evidence-based, but controversial, policy changes in the retail environment. PMID- 26270305 TI - Suicide Rates and State Laws Regulating Access and Exposure to Handguns. AB - OBJECTIVES: Using previous research, we examined the impact of 4 handgun laws (waiting periods, universal background checks, gun locks, and open carrying regulations) on suicide rates. METHODS: We used publicly available databases to collect information on statewide laws, suicide rates, and demographic characteristics for 2013. RESULTS: Each law was associated with significantly lower firearm suicide rates and the proportion of suicides resulting from firearms. In addition, each law, except for that which required a waiting period, was associated with a lower overall suicide rate. Follow-up analyses showed a significant indirect effect on overall suicide rates through the proportion of suicides by firearms, indicating that the reduced overall suicide rate was attributable to fewer suicide attempts, fewer handguns in the home, suicide attempts using less lethal means, or a combination of these factors. States that implemented any of these laws saw a decreased suicide rate in subsequent years, whereas the only state that repealed 1 of these laws saw an increased suicide rate. CONCLUSIONS: Our results were supportive of a potentially vital role in suicide prevention for state legislation that limits access and exposure to handguns. PMID- 26270307 TI - Disparities in Water and Sewer Services in North Carolina: An Analysis of the Decision-Making Process. AB - OBJECTIVES: We examined the factors that affect access to municipal water and sewer service for unincorporated communities relying on wells and septic tanks. METHODS: Using a multisite case study design, we conducted in-depth, semistructured interviews with 25 key informants from 3 unincorporated communities in Hoke, New Hanover, and Transylvania counties, North Carolina, July through September 2013. Interviewees included elected officials, health officials, utility providers, and community members. We coded the interviews in ATLAS.ti to identify common themes. RESULTS: Financing for water and sewer service emerged as the predominant factor that influenced decisions to extend these services. Improved health emerged as a minor factor, suggesting that local officials may not place a high emphasis on the health benefits of extending public water and sewer services. Awareness of failed septic systems in communities can prompt city officials to extend sewer service to these areas; however, failed systems are often underreported. CONCLUSIONS: Understanding the health costs and benefits of water and sewer extension and integrating these findings into the local decision-making process may help address disparities in access to municipal services. PMID- 26270306 TI - Effectiveness of Lay Health Worker Outreach in Reducing Disparities in Colorectal Cancer Screening in Vietnamese Americans. AB - OBJECTIVES: We conducted a cluster randomized controlled study of a lay health worker (LHW) intervention to increase colorectal cancer (CRC) screening rates among Vietnamese Americans, who typically have lower rates than do non-Hispanic Whites. METHODS: We randomized 64 LHWs to 2 arms. Each LHW recruited 10 male or female participants who had never had CRC screening (fecal occult blood test, sigmoidoscopy, or colonoscopy). Intervention LHWs led 2 educational sessions on CRC screening. Control LHWs led 2 sessions on healthy eating and physical activity. The main outcome was self-reported receipt of any CRC screening at 6 months after the intervention. We conducted the study from 2008 to 2013 in Santa Clara County, California. RESULTS: A greater proportion of intervention participants (56%) than control participants (19%) reported receiving CRC screening (P < .001). When controlling for demographic characteristics, the intervention odds ratio was 5.45 (95% confidence interval = 3.02, 9.82). There was no difference in intervention effect by participant gender. CONCLUSIONS: LHW outreach was effective in increasing CRC screening in Vietnamese Americans. Randomized controlled trials are needed to test the effectiveness of LHW outreach for other populations and other health outcomes. PMID- 26270308 TI - Food Insecurity and Cost-Related Medication Underuse Among Nonelderly Adults in a Nationally Representative Sample. AB - OBJECTIVES: We investigated whether nonelderly US adults (aged 18-64 years) in food-insecure households are more likely to report cost-related medication underuse than the food-secure, and whether the relationship between food insecurity and cost-related medication underuse differs by gender, chronic disease, and health insurance status. METHODS: We analyzed data from the 2011 and 2012 National Health Interview Survey (n = 67 539). We examined the relationship between food insecurity and cost-related medication underuse with the chi(2) test and multivariate logistic regression with interaction terms. RESULTS: Bivariate and multivariate analyses showed a dose-response relationship between food insecurity and cost-related medication underuse, with an increasing likelihood of cost-related medication underuse with increasing severity of food insecurity (P < .001). This association was conditional on health insurance status, but not substantially different by gender or chronic disease status. Being female, low income, having no or partial health insurance, chronic conditions, functional limitations, or severe mental illness were positively associated with cost related medication underuse. CONCLUSIONS: Using food insecurity as a risk factor to assess cost-related medication underuse could help increase identification of individuals who may need assistance purchasing medications and improve health for those in food-insecure households. PMID- 26270309 TI - Kenney et al. Respond. PMID- 26270310 TI - Sharing a Playbook: Integrated Care in Community Health Centers in the United States. AB - OBJECTIVES: We investigated basic measures used to assess collaboration between colocated providers and to gauge the extent to which health centers practice integrated care. METHODS: We used the Assessment of Behavioral Health Services survey and the 2010 Uniform Data System to explore the elements of integrated care for behavioral health conditions. We used multivariable regression models to examine the correlates of integrated care. RESULTS: More than 85% of health centers provided mental health services in 2010, and almost half offered substance use treatment. Health centers commonly reported shared access to information among behavioral health and medical providers and joint care planning. A higher degree of integrated care involving joint case conferences was less common. Health centers without electronic health records and those with lower percentages of total staff composed of behavioral health workers were less likely to provide integrated care. CONCLUSIONS: A 2-pronged strategy involving financial incentives and technical assistance to spread best practices might increase integrated care, particularly among health centers that are not maximizing the potential of electronic health records and health centers with low behavioral health staffing levels. PMID- 26270311 TI - Implementation Science and the Criminal Justice System. PMID- 26270312 TI - Nguyen et al. Respond. PMID- 26270313 TI - Health Disparities in and Transdisciplinary Approach to Cardiovascular Disease in Mexico. PMID- 26270314 TI - Inadequate Hydration or Normal Body Fluid Homeostasis? PMID- 26270315 TI - Modeling the Movement of Homicide by Type to Inform Public Health Prevention Efforts. AB - OBJECTIVES: We modeled the spatiotemporal movement of hotspot clusters of homicide by motive in Newark, New Jersey, to investigate whether different homicide types have different patterns of clustering and movement. METHODS: We obtained homicide data from the Newark Police Department Homicide Unit's investigative files from 1997 through 2007 (n = 560). We geocoded the address at which each homicide victim was found and recorded the date of and the motive for the homicide. We used cluster detection software to model the spatiotemporal movement of statistically significant homicide clusters by motive, using census tract and month of occurrence as the spatial and temporal units of analysis. RESULTS: Gang-motivated homicides showed evidence of clustering and diffusion through Newark. Additionally, gang-motivated homicide clusters overlapped to a degree with revenge and drug-motivated homicide clusters. Escalating dispute and nonintimate familial homicides clustered; however, there was no evidence of diffusion. Intimate partner and robbery homicides did not cluster. CONCLUSIONS: By tracking how homicide types diffuse through communities and determining which places have ongoing or emerging homicide problems by type, we can better inform the deployment of prevention and intervention efforts. PMID- 26270316 TI - Firearm Prevalence and Homicides of Law Enforcement Officers in the United States. AB - OBJECTIVES: In the United States, state firearm ownership has been correlated with homicide rates. More than 90% of homicides of law enforcement officers (LEOs) are committed with firearms. We examined the relationship between state firearm ownership rates and LEO occupational homicide rates. METHODS: We obtained the number LEOs killed from 1996 to 2010 from a Federal Bureau of Investigation (FBI) database. We calculated homicide rates per state as the number of officers killed per number of LEOs per state, obtained from another FBI database. We obtained the mean household firearm ownership for each state from the Behavioral Risk Factor Surveillance System. RESULTS: Using Poisson regression and controlling for factors known to affect homicide rates, we associated firearm ownership with the homicide rates for LEOs (incidence rate ratio = 1.044; P = .005); our results were supported by cross-sectional and longitudinal sensitivity analyses. LEO homicide rates were 3 times higher in states with high firearm ownership compared with states with low firearm ownership. CONCLUSIONS: High public gun ownership is a risk for occupational mortality for LEOs in the United States. States could consider methods for reducing firearm ownership as a way to reduce occupational deaths of LEOs. PMID- 26270317 TI - Declining Trends and Widening Disparities in Overweight and Obesity Prevalence Among Massachusetts Public School Districts, 2009-2014. AB - OBJECTIVES: We evaluated the overall and sociodemographic disparities in trends in prevalence of childhood overweight and obesity in Massachusetts public school districts between 2009 and 2014. METHODS: In 2009, Massachusetts mandated annual screening of body mass index for students in grades 1, 4, 7, and 10. This was part of the statewide Mass in Motion prevention programs. We assessed trends in the prevalence of overweight and obesity between 2009 and 2014 by district, gender, grade, and district income. RESULTS: From 2009 to 2014, prevalence decreased 3.0 percentage points (from 34.3% to 31.3%) statewide. The 2014 district-level rates ranged from 13.9% to 54.5% (median = 31.2%). When stratified by grade, the decreasing trends were significant only for grades 1 and 4. Although rates of districts with a median household income greater than $37, 000 improved notably, rates of the poorest remain unchanged and were approximately 40%. CONCLUSIONS: Although overall prevalence began to decrease, the geographic and socioeconomic disparities in childhood obesity are widening and remain a public health challenge in Massachusetts. Special efforts should be made to address the needs of socioeconomically disadvantaged districts and to narrow the disparities in childhood obesity. PMID- 26270318 TI - Hormone therapy in menopause: An update on cardiovascular disease considerations. AB - Cardiovascular disease (CVD) remains the number one cause of death and morbidity worldwide, and while overall CVD incidence rates declined in both genders between 1999 and 2007, age-specific data suggest that coronary risk factors in women are on the rise. While early observational data favored menopausal hormone therapy's (MHT's) role in primary CVD prevention, the initial interventional study data from the WHI did not. Further detailed analyses of both observational and interventional data have pointed to the possibility that MHT may play a role in primary CVD prevention if initiated within 10 years of menopause and less than 60 years of age (the timing hypothesis). Unanswered questions remain regarding the optimal route and dosage of estrogen in MHT. Data so far, favor transdermal estradiol over conventional-dose CEE with respect to CVD risk and oral estradiol over conventional-dose CEE with respect to stroke risk. Low-dose oral CEE may similarly have benefit over conventional-dose oral CEE for some CVD events. In addition, the transdermal route of delivery may avoid the excess risk of certain CVD events associated with MHT and lower doses of estrogen may have fewer adverse effects than the doses previously tested in WHI. Because questions regarding benefits versus risks remain, MHT is yet to be recommended for CVD prevention. However, it is indicated for menopausal symptom management in women within 10 years of menopause and under the age of 60 years, in whom it does not appear to carry increased cardiovascular risk. Additional research is ongoing and needed to confirm or refute the comparative safety of the various MHT options. PMID- 26270319 TI - MY APPROACH to the management of cardiogenic shock. PMID- 26270320 TI - MY APPROACH to device therapy when the battery runs low (replacement or no replacement). PMID- 26270321 TI - MY APPROACH to ventricular tachycardia. PMID- 26270322 TI - Children's contact with people with disabilities and their attitudes towards disability: a cross-sectional study. AB - PURPOSE: To explore the association between children's self-reported contact with people with disabilities and attitudes towards them, as well the potential mediating influence of anxiety about interacting with people with disabilities and empathy for them. METHOD: 1881 children, aged 7-16 years, from 20 schools in South West England completed a survey assessing their contact with people with disabilities and their attitudes towards them. Anxiety about interacting with people with disabilities and empathy towards them were examined as potential mediators. Gender, school year, perceived similarity between people with and without disabilities, proportion of children with additional needs at the school and socioeconomic status (SES) were assessed as moderators. A random effects ("multilevel") regression model was used to test the contact-attitude association and moderation, and path analysis was used to test for mediation. RESULTS: Participants with more self-reported contact reported more positive attitudes towards disability (p < 0.001). Less anticipated anxiety and greater empathy together mediated around a third of this association. Only school year moderated the contact-attitude association (affective attitudes), with stronger contact attitude associations in primary school children than secondary school children. CONCLUSIONS: Self-reported contact was observed to be associated with more positive attitudes towards disability, which was partially mediated by empathy and anxiety. Providing opportunities for contact with people with disabilities that reduces anxiety and increases empathy may improve attitudes to disability and merits evaluation in interventions. Implications for Rehabilitation Children who reported greater levels of contact with people with disabilities had more positive attitudes towards disability. Anxiety about interacting with people with disabilities and empathy towards them partially mediated the contact-attitude associations. Providing opportunities for contact with people with disabilities, reducing anxiety and increasing empathy may improve children's attitudes to disability. PMID- 26270324 TI - Psychological Predictors of Outcomes with Lumbar Spinal Fusion: A Systematic Literature Review. AB - PURPOSE: To review the predictive/risk psychological factors at baseline that are associated with a favourable (or non-favourable) outcome following lumbar spinal fusion (LSF). METHODS: A computer-assisted literature search of PubMed, CINAHL complete and EMBASE for studies published between January 1, 1990 and October 1, 2014 with controlled vocabulary and key words related to LSF, degenerative lumbar spine diagnoses and appropriate terms for predictive variables. Each study was required to be a retrospective or prospective design that involved LSF (all forms). Quality assessment was conducted with the Quality In Prognosis Studies tool. A study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO# CRD42014008728). RESULTS: The majority of the eight accepted studies were observational, prospective cohorts (n = 6). High levels of baseline depression and lower SF-36 Mental Component Scores (MCS) lower quality of life were associated with non-favourable outcomes. Two studies were rated as high quality, five were moderate and one study had low quality. CONCLUSIONS: At present, there are a number of psychological variables that are associated with a poorer outcome with LSF. Higher levels of depression and lower scores on the SF-36 MCS are the most commonly implicated. However, based on the results of the studies using single arm designs there is not enough evidence to determine which psychological variables are influential in predicting outcomes for LSF. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26270323 TI - Footwear and Foam Surface Alter Gait Initiation of Typical Subjects. AB - Gait initiation is the task commonly used to investigate the anticipatory postural adjustments necessary to begin a new gait cycle from the standing position. In this study, we analyzed whether and how foot-floor interface characteristics influence the gait initiation process. For this purpose, 25 undergraduate students were evaluated while performing a gait initiation task in three experimental conditions: barefoot on a hard surface (barefoot condition), barefoot on a soft surface (foam condition), and shod on a hard surface (shod condition). Two force plates were used to acquire ground reaction forces and moments for each foot separately. A statistical parametric mapping (SPM) analysis was performed in COP time series. We compared the anterior-posterior (AP) and medial-lateral (ML) resultant center of pressure (COP) paths and average velocities, the force peaks under the right and left foot, and the COP integral x force impulse for three different phases: the anticipatory postural adjustment (APA) phase (Phase 1), the swing-foot unloading phase (Phase 2), and the support foot unloading phase (Phase 3). In Phase 1, significantly smaller ML COP paths and velocities were found for the shod condition compared to the barefoot and foam conditions. Significantly smaller ML COP paths were also found in Phase 2 for the shod condition compared to the barefoot and foam conditions. In Phase 3, increased AP COP velocities were found for the shod condition compared to the barefoot and foam conditions. SPM analysis revealed significant differences for vector COP time series in the shod condition compared to the barefoot and foam conditions. The foam condition limited the impulse-generating capacity of COP shift and produced smaller ML force peaks, resulting in limitations to body weight transfer from the swing to the support foot. The results suggest that footwear and a soft surface affect COP and impose certain features of gait initiation, especially in the ML direction of Phase 1. PMID- 26270328 TI - Single molecule array (Simoa) assay with optimal antibody pairs for cytokine detection in human serum samples. AB - Concentrations of cytokines in bodily fluids reflect the physiological or pathological state of the patient and can be used for prognosis, disease diagnosis or for monitoring therapeutic efficacy. However, in the bodily fluids of healthy or sub-healthy individuals, many cytokines are present at concentrations that are near or below the detection limits of current methods. Here we selected antibody pairs to be employed in the single molecule array (Simoa) assay for ten cytokines including GM-CSF, TNF-alpha, IFN-gamma, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, and IL-10. The limits of detection (LODs) obtained were as low as 90 aM-6 fM. These assays allow detection of cytokines in healthy human serum samples at levels significantly below the detection limits of conventional ELISA assays. We provide detailed antibody pair information as well as the concentration profiles of ten cytokines in healthy human serum to serve as reference data for further ultrasensitive immunoassay development and future clinical applications. PMID- 26270327 TI - Late emergence of A594V and L595W mutations related to ganciclovir resistance in a patient with HCMV retinitis and long-term HIV progression. AB - The emergence of ganciclovir (GCV) resistance during the treatment of human cytomegalovirus (HCMV) infection is a serious clinical challenge, and is associated with high morbidity and mortality. In this case report, we describe the emergence of two consecutive mutations (A594V and L595W) related to GCV resistance in a patient with HCMV retinitis and long-term HIV progression after approximately 240 days of GCV use. Following the diagnosis of retinitis, the introduction of GCV did not result in viral load reduction. The detected mutations appeared late in the treatment, and we propose that other factors (high initial HCMV load, previous GCV exposure, low CD4+ cell count), in addition to the presence of resistance mutations, may have contributed to the treatment failure of HCMV infection in this patient. PMID- 26270329 TI - Palladium(ii) mononuclear and palladium(ii)/ruthenium(ii) heterodinuclear complexes containing 2-quinolyl-substituted (pyridine-2-carbonyl)hydrazone. AB - A reaction of [PdCl2(cod)] (cod = 1,5-cyclooctadiene) and an E/Z mixture of quinoline-2-carbaldehyde (pyridine-2-carbonyl)hydrazone (HL) gave two kinds of Pd(II) mononuclear complexes, [PdCl(Z-L-kappa(3)N,N',N'')] (1) and [PdCl2(E-HL' kappa(2)N,N')] (2), where L(-) is the deprotonated hydrazonate anion and HL' is the quinolinium-hydrazonate zwitterionic form of HL. Complex 2 is gradually converted to 1 in solution, and complex 1 is a good precursor to prepare a Pd(II)/Ru(II) heterodinuclear complex bridged by hydrazonate, trans(Cl,Cl) [RuCl2(PPh3)2(MU-L)PdCl] (3). PMID- 26270331 TI - EMS Provider Attitudes and Perceptions of Enrolling Patients without Consent in Prehospital Emergency Research. AB - The purpose of this study was to evaluate the attitudes and opinions of a broad population of EMS providers on enrolling patients in research without consent. A survey was conducted in 2010 of all EMS providers who participated in the National Registry of Emergency Medical Technicians (NREMT) reregistration process, which included half of all registered providers. Each reregistration packet included our optional survey, which had nine 6-point Likert scale questions concerning their opinion of research studies without consent as well as 8 demographic questions. Responses were collapsed to agree and disagree and then analyzed using descriptive statistics with 99% confidence intervals. A total of 65,993 EMS providers received the survey and 23,832 (36%) participated. Most respondents agreed (98.4%, 99%CI: 98.2-98.6) that EMS research is important, but only 30.9% (99%CI: 30.1-31.6) agreed with enrolling patients without their consent when it is important to learn about a new treatment. Only 46.6% (99%Cl: 45.7-47.4) were personally willing to be enrolled in a study without their consent. A majority (68.5% [99%Cl: 67.7-69.3]) of respondents believed that EMS providers should have the individual right to refuse to enroll patients in EMS research. While the majority of respondents agreed that EMS research is important, considerably less agree with enrolling patients without consent and less than half would be willing to be enrolled in a study without their consent. Prior to starting an Exception from Informed Consent (EFIC) study, researchers should discuss with EMS providers their perceptions of enrolling patients without consent and address their concerns. PMID- 26270330 TI - A Computational Study of Nasal Spray Deposition Pattern in Four Ethnic Groups. AB - BACKGROUND: Very little is known about the role of nasal morphology due to ethnic variation on particle deposition pattern in the sinonasal cavity. This preliminary study utilizes computational fluid dynamics (CFD) modeling to investigate sinonasal airway morphology and deposition patterns of intranasal sprayed particles in the nose and sinuses of individuals from four different ethnic groups: African American (Black); Asian; Caucasian; and Latin American. METHODS: Sixteen subjects (four from each ethnic group) with "normal" sinus protocol computed tomography (CT) were selected for CFD analysis. Three dimensional reconstruction of each subject's sinonasal cavity was created from their personal CT images. CFD simulations were carried out in ANSYS Fluent(TM) in two phases: airflow phase was done by numerically solving the Navier-Stokes equations for steady state laminar inhalation; and particle dispersed phase was solved by tracking injected (sprayed) particles through the calculated airflow field. A total of 10,000 particle streams were released from each nostril, 1000 particles per diameter ranging from 5 MUm to 50 MUm, with size increments of 5 MUm. RESULTS: As reported in the literature, Caucasians (5.31 +/- 0.42 cm(-1)) and Latin Americans (5.16 +/- 0.40cm(-1)) had the highest surface area to volume ratio, while African Americans had highest nasal index (95.91 +/- 2.22). Nasal resistance (NR) was highest among Caucasians (0.046 +/- 0.008 Pa.s/mL) and Asians (0.042 +/- 0.016Pa.s/mL). Asians and African Americans had the most regions with particle deposition for small (5 MUm-15 MUm) and large (20 MUm-50 MUm) particle sizes, respectively. Asians and Latin Americans individuals had the most consistent regional particle deposition pattern in the main nasal cavities within their respective ethnic groups. CONCLUSIONS: Preliminary results from these ethnic groups investigated showed that Caucasians and Latin Americans had the least patent nasal cavity. Furthermore, Caucasians and African Americans had the lowest inter-subject consistency in regional particle deposition pattern; this may be due to greater inter-subject variability in their respective nasal vestibule morphology. PMID- 26270332 TI - Concentric Magnetic Structures for Magnetophoretic Bead Collection, Cell Trapping and Analysis of Cell Morphological Changes Caused by Local Magnetic Forces. AB - Concentric magnetic structures (ring and square) with domain wall (DW) pinning geometry are designed for biological manipulation. Magnetic beads collection was firstly demonstrated to analyse the local magnetic field generated by DWs and the effective regions to capture magnetic targets of size 1 MUm. Primary mouse embryonic fibroblasts (MEFs) are magnetically labeled by internalizing poly (styrene sulfonic acid) stabilized magnetic nanoparticles (PSS-MNPs) and then are selectively trapped by head-to-tail DWs (HH DWs) or tail-to-tail DWs (TT DWs) to be arranged into linear shape or cross shape. The morphologies and the nuclear geometry of the cells growing on two kinds of concentric magnetic structures are shown to be distinctive. The intracellular magnetic forces generated by the local magnetic field of DWs are found to influence the behaviour of cells. PMID- 26270334 TI - Correction: Copper Pollution Increases the Relative Importance of Predation Risk in an Aquatic Food Web. PMID- 26270333 TI - Functional Leaf Traits and Diurnal Dynamics of Photosynthetic Parameters Predict the Behavior of Grapevine Varieties Towards Ozone. AB - A comparative study on functional leaf treats and the diurnal dynamics of photosynthetic processes was conducted on 2-year-old potted plants of two grape (Vitis vinifera L.) varieties (Aleatico, ALE, and Trebbiano giallo, TRE), exposed under controlled conditions to realistic concentrations of the pollutant gas ozone (80 ppb for 5 h day(-1), 8:00-13:00 h, + 40 ppb for 5 h day(-1), 13:00 18:00 h). At constitutive levels, the morphological functional traits of TRE improved leaf resistance to gas exchange, suggesting that TRE is characterized by a potential high degree of tolerance to ozone. At the end of the treatment, both varieties showed typical visible injuries on fully expanded leaves and a marked alteration in the diurnal pattern of photosynthetic activity. This was mainly due to a decreased stomatal conductance (-27 and -29% in ALE and TRE, in terms of daily values in comparison to controls) and to a reduced mesophyllic functioning (+33 and +16% of the intercellular carbon dioxide concentration). Although the genotypic variability of grape regulates the response to oxidative stress, similar detoxification processes were activated, such as an increased content of total carotenoids (+64 and +30%, in ALE and TRE), enhanced efficiency of thermal energy dissipation within photosystem II (+32 and +20%) closely correlated with the increased de-epoxidation index (+26 and +22%) and variations in content of some osmolytes. In summary, we can conclude that: the daily photosynthetic performance of grapevine leaves was affected by a realistic exposure to ozone. In addition, the gas exchange and chlorophyll a fluorescence measurements revealed a different quali-quantitative response in the two varieties. The genotypic variability of V. vinifera and the functional leaf traits would seem to regulate the acclimatory response to oxidative stress and the degree of tolerance to ozone. Similar photoprotective mechanisms were activated in the two varieties, though to a different extent. PMID- 26270335 TI - Antiprotozoal Activity Profiling of Approved Drugs: A Starting Point toward Drug Repositioning. AB - Neglected tropical diseases cause significant morbidity and mortality and are a source of poverty in endemic countries. Only a few drugs are available to treat diseases such as leishmaniasis, Chagas' disease, human African trypanosomiasis and malaria. Since drug development is lengthy and expensive, a drug repurposing strategy offers an attractive fast-track approach to speed up the process. A set of 100 registered drugs with drug repositioning potential for neglected diseases was assembled and tested in vitro against four protozoan parasites associated with the aforementioned diseases. Several drugs and drug classes showed in vitro activity in those screening assays. The results are critically reviewed and discussed in the perspective of a follow-up drug repositioning strategy where R&D has to be addressed with limited resources. PMID- 26270337 TI - Determination of Race from the Skeleton through Forensic Anthropological Methods. AB - Metric and morphological techniques employed by forensic anthropologists for determination of race are reviewed. Included are several studies which examine cranial morphological techniques such as presence of the oval window of the inner ear, which occurs more frequently in Whites than in Native Americans; or the shape of the alveolar region which distinguishes between Asian, African, and North American Indian groups. A table of common cranial morphologic traits is presented. Metric techniques have also been used to determine race from the skull. Regression equations derived from measurements of the cranial base indicate a 70-90% accuracy for classifying Blacks and Whites, while multivariate discriminant functions for discriminating Blacks, Whites, and Native Americans correctly classify 82.6% of the males and 88.1% of the females. FORDISC, a computer program developed at the University of Tennessee, is another metric technique reviewed that not only distinguishes Whites, Blacks, and Native Americans but also male Hispanics, Chinese, and Vietnamese. Platycnemia, femoral curvature and other morphological attributes of the post-cranial skeleton may be used in support of a racial determination; however, several investigators have turned to post-cranial elements not only to use in support of cranial findings but for use when cranial information is not available. As a result, several discriminant functions from measurements of the pelvis, femur, tibia or combinations of these elements have been developed. Accuracy for these techniques varies from 57% to 95%, depending on the sample and technique used. Other aspects of the femur, such as the diameter of the neck, height of the intercondylar notch and femoral curvature, have been measured for assessment of race. Also included is a brief historical survey of race and current thoughts on the concept of race. PMID- 26270338 TI - Medical Review Officer Interpretation of Urine Drug Test Results. AB - Federal regulations, some state statutes, and company programs have created a position for physicians to serve as medical review officers and interpret urine drug test results. This article is intended to provide the medical review officer with an overview of commonly-tested drugs and factors that may affect analytical results. In addition, the sources of legitimate explanations for a positive test are discussed. Legitimate explanations may include the use of prescription and non-prescription medication, foodstuffs, occupational exposure to drugs, and drugs that metabolize to substances that are tested. Physicians serving as medical review officers must be familiar with the legal, medical, and toxicological issues of urine drug testing. PMID- 26270339 TI - Criminalistics Education and the Role of the Criminalistics Educator. AB - The uniqueness of criminalistics education stems from the participation of academe, laboratories, and a variety of public agencies, professional associations, and private vendors. One consequence of laboratory and association participation is the premium placed on experience during the evaluation process. An analysis of undergraduate criminalistics programs indicates the existence of considerable reservations about their utility for providing new laboratory personnel. At the masters degree level, however, a consensus appears to exist about the appropriateness of curricular structure and the value of a graduate degree in criminalistics for laboratory employment. Doctoral programs related to criminalistics are also discussed and the need for their maintenance is emphasized. The review concludes with an examination of the role of the criminalistics educator as: academic leader, agent of institutional change, laboratory counter-balance, and catalyst for legal change. PMID- 26270336 TI - Outcome after Reconstruction of the Proximal Tibia--Complications and Competing Risk Analysis. AB - BACKGROUND AND OBJECTIVES: The proximal tibia (pT) is a common site for bone tumors. Improvements in imaging, chemotherapy and surgical technique made limb salvage surgery the treatment of choice. Yet, reconstructions of the pT have been associated with less favorable outcome compared to other parts of the extremities. The aim of this study was to evaluate the outcome of patients with a modular endoprosthetic reconstruction of the pT. METHODS: Eighty-one consecutive patients with an average age of 29 years underwent endoprosthetic reconstruction of the pT. Postoperative complications were categorized according to the ISOLS classification, and revision-free survival until first complication (any Type 1 5), soft tissue failure (Type 1), aseptic loosening (Type 2), structural failure (Type 3), infection (Type 4), and local tumor progression (Type 5) was estimated by using a Fine-Gray model for competing risk analyses for univariate and multivariable regression with Firth's bias correction. RESULTS: A total of 45 patients (56%) had at least one complication. Cumulative incidence for complication Types 1 to 5 at 5 years with death and amputation as competing events revealed a risk of 41% for the first complication, 14% for Type 1, 16% for Type 2, 11% for Type 3, 17% for Type 4, and 1% for Type 5. CONCLUSION: Despite inclusion of amputation and death as strong competing events, pT replacements are still associated with a high risk of postoperative failures. The results suggest that infection and soft tissue failures (Type 1 and 5) seem to depend from each other. Sufficient soft tissue reconstruction and closure allow better function and reduce the risk of infection as the most prominent complication. The use of a rotating hinge design has significantly reduced structural failures over time. PMID- 26270340 TI - Late Conversion of Kidney Transplant Recipients from Ciclosporin to Tacrolimus Improves Graft Function: Results from a Randomized Controlled Trial. AB - BACKGROUND: Tacrolimus (TAC) to ciclosporin A (CSA) conversion studies in stable kidney transplant recipients have reported varying effects on graft function. Here we study graft function (eGFR) trajectories using linear mixed models, which provide effect estimates on both slope and baseline level of GFR and offer increased statistical power. METHODS: Secondary analysis of a randomized controlled trial of CSA treated kidney transplant recipients with stable graft function assigned to receive 0.1 mg/kg/day TAC (target 5-8 ng/ml) or to continue CSA based immunosuppression (target 70-150 ng/ml) at a 2:1 ratio. Renal graft function was estimated via the MDRD (eGFRMDRD) and CKD-EPI (eGFRCKD-EPI) formulas. RESULTS: Forty-five patients continued CSA and 96 patients were converted to TAC with a median follow up of 24 months. Baseline demographics (except for recipient age) including native kidney disease, transplant characteristics, kidney graft function, medication use and comorbid conditions did not differ between groups. In respect to long-term renal graft function, linear mixed models showed significantly improved eGFR trajectories (eGFRMDRD: p<0.001, eGFRCKD-EPI: p<0.001) in the TAC versus CSA group over 24 months of follow up. Estimated eGFRCKD-EPI group differences between TAC and CSA were -3.49 (p = 0.019) at 3 months, -5.50 (p<0.001) at 12 months, and -4.48 ml/min/1.73m2 (p = 0.003) at 24 months of follow up. Baseline eGFR was a significant predictor of eGFR trajectories (eGFRMDRD: p<0.001, eGFRCKD-EPI: p<0.001). Significant effects for randomization group were evident despite short-term trough levels in the supratherapeutic range (27% (n = 26) of TAC patients at week one). Median TAC trough levels were within target range at week 4 after conversion. CONCLUSION: Conversion of CSA treated kidney transplant recipients with stable graft function to TAC (target 5-8 ng/ml) showed significantly improved long-term eGFR trajectories when compared to CSA maintenance (target 70-150 ng/ml). TRIAL REGISTRATION: ClinicalTrials.gov NCT00182559 EudraCT identifier: 2004-004209-98. PMID- 26270341 TI - Subset Analysis of a Multicenter, Randomized Controlled Trial to Compare Magnifying Chromoendoscopy with Endoscopic Ultrasonography for Stage Diagnosis of Early Stage Colorectal Cancer. AB - BACKGROUND: Our recent prospective study found equivalent accuracy of magnifying chromoendoscopy (MC) and endoscopic ultrasonography (EUS) for diagnosing the invasion depth of colorectal cancer (CRC); however, whether these tools show diagnostic differences in categories such as tumor size and morphology remains unclear. Hence, we conducted detailed subset analysis of the prospective data. METHODS: In this multicenter, prospective, comparative trial, a total of 70 patients with early, flat CRC were enrolled from February 2011 to December 2012, and the results of 66 lesions were finally analyzed. Patients were randomly allocated to primary MC followed by EUS or to primary EUS followed by MC. Diagnoses of invasion depth by each tool were divided into intramucosal to slight submucosal invasion (invasion depth <1000 MUm) and deep submucosal invasion (invasion depth >=1000 MUm), and then compared with the final pathological diagnosis by an independent pathologist blinded to clinical data. To standardize diagnoses among examiners, this trial was started after achievement of a mean kappa value of >=0.6 which was calculated from the average of kappa values between each pair of participating endoscopists. RESULTS: Both MC and EUS showed similar diagnostic outcomes, with no significant differences in prediction of invasion depth in subset analyses according to tumor size, location, and morphology. Lesions that were consistently diagnosed as Tis/T1-SMS or >=T1-SMD with both tools revealed accuracy of 76-78%. Accuracy was low in borderline lesions with irregular pit pattern in MC and distorted findings of the third layer in EUS (MC, 58.5%; EUS, 50.0%). CONCLUSIONS: MC and EUS showed the same limited accuracy for predicting invasion depth in all categories of early CRC. Since the irregular pit pattern in MC, distorted findings to the third layer in EUS and inconsistent diagnosis between both tools were associated with low accuracy, further refinements or even novel methods are still needed for such lesions. TRIAL REGISTRATION: University hospital Medical Information Network Clinical Trials Registry UMIN 000005085. PMID- 26270343 TI - Is a Cholera Outbreak Preventable in Post-earthquake Nepal? PMID- 26270342 TI - The Centipede Genus Scolopendra in Mainland Southeast Asia: Molecular Phylogenetics, Geometric Morphometrics and External Morphology as Tools for Species Delimitation. AB - Seven Scolopendra species from the Southeast Asian mainland delimited based on standard external morphological characters represent monophyletic groups in phylogenetic trees inferred from concatenated sequences of three gene fragments (cytochrome c oxidase subunit 1, 16S rRNA and 28S rRNA) using Maximum likelihood and Bayesian inference. Geometric morphometric description of shape variation in the cephalic plate, forcipular coxosternite, and tergite of the ultimate leg bearing segment provides additional criteria for distinguishing species. Colouration patterns in some Scolopendra species show a high degree of fit to phylogenetic trees at the population level. The most densely sampled species, Scolopendra dehaani Brandt, 1840, has three subclades with allopatric distributions in mainland SE Asia. The molecular phylogeny of S. pinguis Pocock, 1891, indicated ontogenetic colour variation among its populations. The taxonomic validation of S. dawydoffi Kronmuller, 2012, S. japonica Koch, 1878, and S. dehaani Brandt, 1840, each a former subspecies of S. subspinipes Leach, 1814 sensu Lewis, 2010, as full species was supported by molecular information and additional morphological data. Species delimitation in these taxonomically challenging animals is facilitated by an integrative approach that draws on both morphology and molecular phylogeny. PMID- 26270344 TI - R54C Mutation of NOTCH3 Gene in the First Rungus Family with CADASIL. AB - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary stroke caused by mutations in NOTCH3 gene. We report the first case of CADASIL in an indigenous Rungus (Kadazan Dusun) family in Kudat, Sabah, Malaysia confirmed by a R54C (c.160C>T, p.Arg54Cys) mutation in the NOTCH3. This mutation was previously reported in a Caucasian and two Korean cases of CADASIL. We recruited two generations of the affected Rungus family (n = 9) and found a missense mutation (c.160C>T) in exon 2 of NOTCH3 in three siblings. Two of the three siblings had severe white matter abnormalities in their brain MRI (Scheltens score 33 and 50 respectively), one of whom had a young stroke at the age of 38. The remaining sibling, however, did not show any clinical features of CADASIL and had only minimal changes in her brain MRI (Scheltens score 17). This further emphasized the phenotype variability among family members with the same mutation in CADASIL. This is the first reported family with CADASIL in Rungus subtribe of Kadazan-Dusun ethnicity with a known mutation at exon 2 of NOTCH3. The penetrance of this mutation was not complete during the course of this study. PMID- 26270345 TI - How Heme Oxygenase-1 Prevents Heme-Induced Cell Death. AB - Earlier observations indicate that free heme is selectively toxic to cells lacking heme oxygenase-1 (HO-1) but how this enzyme prevents heme toxicity remains unexplained. Here, using A549 (human lung cancer) and immortalized human bronchial epithelial cells incubated with exogenous heme, we find knock-down of HO-1 using siRNA does promote the accumulation of cell-associated heme and heme induced cell death. However, it appears that the toxic effects of heme are exerted by "loose" (probably intralysosomal) iron because cytotoxic effects of heme are lessened by pre-incubation of HO-1 deficient cells with desferrioxamine (which localizes preferentially in the lysosomal compartment). Desferrioxamine also decreases lysosomal rupture promoted by intracellularly generated hydrogen peroxide. Supporting the importance of endogenous oxidant production, both chemical and siRNA inhibition of catalase activity predisposes HO-1 deficient cells to heme-mediated killing. Importantly, it appears that HO-1 deficiency somehow blocks the induction of ferritin; control cells exposed to heme show ~10 fold increases in ferritin heavy chain expression whereas in heme-exposed HO-1 deficient cells ferritin expression is unchanged. Finally, overexpression of ferritin H chain in HO-1 deficient cells completely prevents heme-induced cytotoxicity. Although two other products of HO-1 activity--CO and bilirubin- have been invoked to explain HO-1-mediated cytoprotection, we conclude that, at least in this experimental system, HO-1 activity triggers the induction of ferritin and the latter is actually responsible for the cytoprotective effects of HO-1 activity. PMID- 26270346 TI - The Expression of the Zonula Adhaerens Protein PLEKHA7 Is Strongly Decreased in High Grade Ductal and Lobular Breast Carcinomas. AB - PLEKHA7 is a junctional protein, which participates in a complex that stabilizes E-cadherin at the zonula adhaerens. Since E-cadherin is involved in epithelial morphogenesis, signaling, and tumor progression, we explored PLEKHA7 expression in cancer. PLEKHA7 expression was assessed in invasive ductal and lobular carcinomas of the breast by immunohistochemistry, immunofluorescence and quantitative RT-PCR. PLEKHA7 was detected at epithelial junctions of normal mammary ducts and lobules, and of tubular and micropapillary structures within G1 and G2 ductal carcinomas. At these junctions, the localization of PLEKHA7 was along the circumferential belt (zonula adhaerens), and only partially overlapping with that of E-cadherin, p120ctn and ZO-1, as shown previously in rodent tissues. PLEKHA7 immunolabeling was strongly decreased in G3 ductal carcinomas and undetectable in lobular carcinomas. PLEKHA7 mRNA was detected in both ductal and lobular carcinomas, with no observed correlation between mRNA levels and tumor type or grade. In summary, PLEKHA7 is a junctional marker of epithelial cells within tubular structures both in normal breast tissue and ductal carcinomas, and since PLEKHA7 protein but not mRNA expression is strongly decreased or lost in high grade ductal carcinomas and in lobular carcinomas, loss of PLEKHA7 is a newly characterized feature of these carcinomas. PMID- 26270347 TI - Relative Risk of Acute Myocardial Infarction in People with Schizophrenia and Bipolar Disorder: A Population-Based Cohort Study. AB - OBJECTIVE: Despite high mortality associated with serious mental illness, risk of acute myocardial infarction (AMI) remains unclear, especially for patients with bipolar disorder. The main objective was to investigate the relative risk of AMI associated with schizophrenia and bipolar disorders in a national sample. METHOD: Using nationwide administrative data, an 11-year historic cohort study was assembled, comprised of cases aged 18 and above who had received a diagnosis of schizophrenia or bipolar disorder, compared to a random sample of all other adults excluding those with diagnoses of serious mental illness. Incident AMI as a primary diagnosis was ascertained. Hazard ratios stratified by age and gender were calculated and Cox regression models were used to adjust for other covariates. RESULTS: A total of 70,225 people with schizophrenia or bipolar disorder and 207,592 people without serious mental illness were compared. Hazard ratios in men adjusted for age, income and urbanization were 1.15 (95% CI 1.01~1.32) for schizophrenia and 1.37 (1.08~1.73)for bipolar disorder, and in women, 1.85 (1.58~2.18) and 1.88(1.47~2.41) respectively. Further adjustment for treated hypertension, diabetes and hyperlipidaemia attenuated the hazard ratio for men with schizophrenia but not the other comparison groups. Hazard ratios were significantly stronger in women than men and were stronger in younger compared to older age groups for both disorders; however, gender modification was only significant in people with schizophrenia, and age modification only significant in people with bipolar disorder. CONCLUSIONS: In this large national sample, schizophrenia and bipolar disorder were associated with raised risk of AMI in women and in the younger age groups although showed differences in potential confounding and modifying factors. PMID- 26270348 TI - Subclinical Hypothyroidism and Type 2 Diabetes: A Systematic Review and Meta Analysis. AB - BACKGROUND: Abundant evidence suggests an association between subclinical hypothyroidism (SCH) and type 2 diabetes mellitus (T2DM), but small sample sizes and inconclusive data in the literature complicate this assertion. OBJECTIVE: We measured the prevalence of SCH in T2DM population, and investigated whether T2DM increase the risk of SCH and whether SCH was associated with diabetic complications. METHODS: We conducted a meta-analysis using PubMed, EMBASE, Web of Science, Wan Fang, CNKI and VIP databases for literature search. We obtained studies published between January 1, 1980 to December 1, 2014. The studies were selected to evaluate the prevalence of SCH in T2DM subjects, compare the prevalence of SCH in T2DM subjects with those non-diabetics, and investigate whether diabetic complications were more prevalent in SCH than those who were euthyroid. Fixed and random effects meta-analysis models were used, and the outcome was presented as a pooled prevalence with 95% confidence interval (95% CI) or a summary odds ratio (OR) with 95% CI. RESULTS: Through literature search, 36 articles met the inclusion criteria and these articles contained a total of 61 studies. Funnel plots and Egger's tests showed no publication bias in our studies, except for the pooled prevalence of SCH in T2DM (P = 0.08) and OR for SCH in T2DM (P = 0.04). Trim and fill method was used to correct the results and five potential missing data were replaced respectively. The adjusted pooled prevalence of SCH in T2DM patients was 10.2%, meanwhile, T2DM was associated with a 1.93-fold increase in risk of SCH (95% CI: 1.66, 2.24). Furthermore, SCH might affect the development of diabetic complications with an overall OR of 1.74 (95% CI: 1.34, 2.28) for diabetic nephropathy, 1.42 (95% CI: 1.21, 1.67) for diabetic retinopathy, 1.85 (95% CI: 1.35, 2.54) for peripheral arterial disease, and 1.87 (95% CI: 1.06, 3.28) for diabetic peripheral neuropathy. CONCLUSIONS: T2DM patients are more likely to have SCH when compared with healthy population and SCH may be associated with increased diabetic complications. It is necessary to screen thyroid function in patients with T2DM, and appropriate individualized treatments in addition to thyroid function test should be given to T2DM patients with SCH as well. PMID- 26270351 TI - Breast Cancer/Stromal Cells Coculture on Polyelectrolyte Films Emulates Tumor Stages and miRNA Profiles of Clinical Samples. AB - In this study, we demonstrate a method for controlling breast cancer cells adhesion on polyelectrolyte multilayer (PEM) films without the aid of adhesive proteins/ligands to study the role of tumor and stromal cell interaction on cancer biology. Numerous studies have explored engineering coculture of tumor and stromal cells predominantly using transwell coculture of stromal cells cultured onto coverslips that were subsequently added to tumor cell cultures. However, these systems imposed an artificial boundary that precluded cell-cell interactions. To our knowledge, this is the first demonstration of patterned coculture of tumor cells and stromal cells that captures the temporal changes in the miRNA signature as the breast tumor develops through various stages. In our study we used synthetic polymers, namely poly(diallyldimethylammonium chloride) (PDAC) and sulfonated poly(styrene) (SPS), as the polycation and polyanion, respectively, to build PEMs. Breast cancer cells attached and spread preferentially on SPS surfaces while stromal cells attached to both SPS and PDAC surfaces. SPS patterns were formed on PEM surfaces, by either capillary force lithography (CFL) of SPS onto PDAC surfaces or vice versa, to obtain patterns of breast cancer cells and patterned cocultures of breast cancer and stromal cells. In this study, we utilized cancer cells derived from two different tumor stages and two different stromal cells to effectively model a heterogeneous tumor microenvironment and emulate various tumor stages. The coculture model mimics the proliferative index (Ki67 expression) and tumor aggressiveness (HER-2 expression) akin to those observed in clinical tumor samples. We also demonstrated that our patterned coculture model captures the temporal changes in the miRNA-21 and miRNA 34 signature as the breast tumor develops through various stages. The engineered coculture platform lays groundwork toward precision medicine wherein patient derived tumor cells can be incorporated within our in vitro models to identify potential pathways and drug treatment regimens for individual patients. PMID- 26270352 TI - Photoactivated cyclases: In memoriam Masakatsu Watanabe. PMID- 26270349 TI - Exploring the role of MKK7 in excitotoxicity and cerebral ischemia: a novel pharmacological strategy against brain injury. AB - Excitotoxicity following cerebral ischemia elicits a molecular cascade, which leads to neuronal death. c-Jun-N-terminal kinase (JNK) has a key role in excitotoxic cell death. We have previously shown that JNK inhibition by a specific cell-permeable peptide significantly reduces infarct size and neuronal death in an in vivo model of cerebral ischemia. However, systemic inhibition of JNK may have detrimental side effects, owing to blockade of its physiological function. Here we designed a new inhibitor peptide (growth arrest and DNA damage inducible 45beta (GADD45beta-I)) targeting mitogen-activated protein kinase kinase 7 (MKK7), an upstream activator of JNK, which exclusively mediates JNK's pathological activation. GADD45beta-I was engineered by optimizing the domain of the GADD45beta, able to bind to MKK7, and by linking it to the TAT peptide sequence, to allow penetration of biological membranes. Our data clearly indicate that GADD45beta-I significantly reduces neuronal death in excitotoxicity induced by either N-methyl-D-aspartate exposure or by oxygen-glucose deprivation in vitro. Moreover, GADD45beta-I exerted neuroprotection in vivo in two models of ischemia, obtained by electrocoagulation and by thromboembolic occlusion of the middle cerebral artery (MCAo). Indeed, GADD45beta-I reduced the infarct size when injected 30 min before the lesion in both models. The peptide was also effective when administrated 6 h after lesion, as demonstrated in the electrocoagulation model. The neuroprotective effect of GADD45beta-I is long lasting; in fact, 1 week after MCAo the infarct volume was still reduced by 49%. Targeting MKK7 could represent a new therapeutic strategy for the treatment of ischemia and other pathologies involving MKK7/JNK activation. Moreover, this new inhibitor can be useful to further dissect the physiological and pathological role of the JNK pathway in the brain. PMID- 26270350 TI - AK2 deficiency compromises the mitochondrial energy metabolism required for differentiation of human neutrophil and lymphoid lineages. AB - Reticular dysgenesis is a human severe combined immunodeficiency that is primarily characterized by profound neutropenia and lymphopenia. The condition is caused by mutations in the adenylate kinase 2 (AK2) gene, resulting in the loss of mitochondrial AK2 protein expression. AK2 regulates the homeostasis of mitochondrial adenine nucleotides (ADP, ATP and AMP) by catalyzing the transfer of high-energy phosphate. Our present results demonstrate that AK2-knocked-down progenitor cells have poor proliferative and survival capacities and are blocked in their differentiation toward lymphoid and granulocyte lineages. We also observed that AK2 deficiency impaired mitochondrial function in general and oxidative phosphorylation in particular - showing that AK2 is critical in the control of energy metabolism. Loss of AK2 disrupts this regulation and leads to a profound block in lymphoid and myeloid cell differentiation. PMID- 26270353 TI - Pharmacokinetic study of enrofloxacin in Nile tilapia (Oreochromis niloticus) after a single oral administration in medicated feed. AB - The objective of this study was to evaluate the disposition kinetics of enrofloxacin (ENR) in the plasma and its distribution in the muscle tissue of Nile tilapia (Oreochromis niloticus) after a single oral dose of 10 mg/kg body weight via medicated feed. The fish were kept at a temperature between 28 and 30 degrees C. The collection period was between 30 min and 120 h after administration of the drug. The samples were analyzed by high-performance liquid chromatography with a fluorescence detector (HPLC-FLD). The ENR was slowly absorbed and eliminated from the plasma (Cmax = 1.24 +/- 0.37 MUg/mL; Tmax = 8 h; T1/2Ke = 19.36 h). ENR was efficiently distributed in the muscle tissue and reached maximum values (2.17 +/- 0.74 MUg/g) after 8 h. Its metabolite, ciprofloxacin (CIP), was detected and quantified in the plasma (0.004 +/- 0.005 MUg/mL) and muscle (0.01 +/- 0.011 MUg/g) for up to 48 h. After oral administration, the mean concentration of ENR in the plasma was well above the minimum inhibitory concentrations (MIC50 ) for most bacteria already isolated from fish except for Streptococcus spp. This way the dose used in this study allowed for concentrations in the blood to treat the diseases of tilapia. PMID- 26270354 TI - Ultrastructural Features of Sperm Storage Tubules in the Oviduct of the Indian Garden Lizard, Calotes Versicolor. AB - This study provides the first description of the ultrastructural features of sperm storage tubules (SSTs) in the uterovaginal region of the oviduct of the Indian garden lizard, Calotes versicolor. Abundant spermatozoa along with copious secretory material were found in the lumen of the SSTs. These secretory granules appeared similar in electron density to those found in the epithelial cells lining the SSTs indicating their similar origin. The close physical proximity of sperm with these granules suggests an intimate association between the two. The present study is also the first report of recovery of motile sperm from the flushings of SSTs in C. versicolor. The density of sperm found in the flushings varied, being most abundant during the reproductive phase and minimum/absent during the regressive phase. Understanding the microenvironment of the SSTs, the nature of the secretory granules and their interaction with sperm can guide us in unraveling the biology of oviductal sperm storage. PMID- 26270356 TI - Water Phase Diagram Is Significantly Altered by Imidazolium Ionic Liquid. AB - We report unusually large changes in the boiling temperature, saturated vapor pressure, and structure of the liquid-vapor interface for a range of 1-butyl-3 methyl tetrafluoroborate, [C4C1IM][BF4]-water mixtures. Even modest molar fractions of [C4C1IM][BF4] significantly affect the phase behavior of water, as represented, for instance, by strong negative deviations from Raoult's law, extending far beyond the standard descriptions. The investigation was carried out using classical molecular dynamics employing a specifically refined force field. The changes in the liquid-vapor interface and saturated vapor pressures are discussed at the atomistic resolution. The reported results guide the search for novel scientific and technological applications of ion-molecular systems. PMID- 26270355 TI - Host stromal versican is essential for cancer-associated fibroblast function to inhibit cancer growth. AB - The stroma provides a microenvironment that regulates tumor cell behavior. The extracellular matrix (ECM) has long been recognized to be important in tumor cell behavior, and previous studies have revealed the impact of individual matrix molecules on tumor progression. Although several reports have highlighted some central roles of tumor cell-expressed versican, the role of host stromal versican is not yet understood. In this study, we demonstrate that versican is an important molecule in the functional ECM structure and maintaining cancer associated fibroblasts, using versican-negative QRsP11 fibrosarcoma cells. By their subcutaneous injection with cre-expressing adenoviruses to versican-floxed mice, we demonstrate that loss of host stromal versican facilitates tumor cell proliferation, and following angiogenesis, decreases cancer-associated fibroblasts, diminishes collagen fibers and alters hyaluronan distribution, concomitant with upregulation of hyaluronan, TGFbeta and VEGF-mediated signaling. When the versican V3 variant consisting of G1 and G3 domains was expressed in tumor cells, it was integrated into the ECM, regained collagen fibers and cancer associated fibroblasts and resulted in successful recovery of tumor growth inhibition, indicating that whatever cells produce, the G1 and G3 domains are adequate for versican function. Collectively, our results indicate a dynamic function of versican in the ECM that regulates tumor cell behavior. A greater understanding of the regulation of versican expression may contribute to the development of cancer therapies. PMID- 26270357 TI - Recombination Study of Combined Halides (Cl, Br, I) Perovskite Solar Cells. AB - We report on the preparation of a series of solution-processed perovskite solar cells based on methylammonium (MA) lead halide derivatives, MAPbX3, which show tunable optical properties depending on the nature and ratio of the halides employed (X = Cl, Br, and I). Devices have been prepared with different cell architecture, thin film, and mesoporous scaffold (TiO2 and Al2O3). We have analyzed different sample sets focusing on the characterization of the charge recombination by means of impedance spectroscopy (IS). On the one hand, our study discloses that the insertion of both Cl and Br in the perovskite lattice reduces the charge recombination rates in the light absorber film, thus determining the open circuit voltage (Voc) of the device. The samples prepared on a mesoporous Al2O3 electrode present lower charge recombination rates than those devices prepared on mesoporous TiO2. Furthermore, the addition of Br in the perovskite structure was demonstrated to improve slightly the lifetime of the devices; in fact, the efficiencies of all devices tested remained at least at the 80% of the initial value 1 month after their preparation. These results highlight the crucial role of the charge-recombination processes on the performance of the perovskite solar cells and pave the way for further progress on this field. PMID- 26270358 TI - Orientation-Dependent Oxygen Evolution Activities of Rutile IrO2 and RuO2. AB - The activities of the oxygen evolution reaction (OER) on IrO2 and RuO2 catalysts are among the highest known to date. However, the intrinsic OER activities of surfaces with defined crystallographic orientations are not well-established experimentally. Here we report that the (100) surface of IrO2 and RuO2 is more active in alkaline environments (pH 13) than the most thermodynamically stable (110) surface. The OER activity was correlated with the density of coordinatively undersaturated metal sites of each crystallographic facet. The surface orientation-dependent activities can guide the design of nanoscale catalysts with increased activity for electrolyzers, metal-air batteries, and photoelectrochemical water splitting applications. PMID- 26270359 TI - Fast Energy Relaxation by Trap States Decreases Electron Mobility in TiO2 Nanotubes: Time-Domain Ab Initio Analysis. AB - Highly ordered TiO2 nanotube arrays can be grown by simple electrochemical anodization of a titanium metal sheet, stimulating intense research and applications to solar cells and fuels. TiO2 nanotubes were expected to exhibit better electron transport than nanocrystal films. However, experiments showed that nanotubes provided little advantage over nanoparticles. Using nonadiabatic molecular dynamics, we demonstrate that oxygen vacancies, which are common in TiO2, accelerate nonradiative energy losses by an order of magnitude. Oxygen vacancies produce localized Ti(3+) states hundreds of millielectronvolts below the TiO2 conduction band. The states lower the nanotube band gap, trap excited electrons, induce stronger electron-phonon couplings, and facilitate the relaxation. Our results rationalize the unforeseen experimental observations and provide the atomistic basis for improving the structure and charge transport by TiO2 nanotubes. PMID- 26270360 TI - Catalytic Cycle Employing a TEMPO-Anion Complex to Obtain a Secondary Mg-O2 Battery. AB - Nonaqueous Mg-O2 batteries are suitable only as primary cells because MgO precipitates formed during discharging are not decomposed electrochemically at ambient temperatures. To address this problem, the present study examined the ability of the 2,2,6,6-tetramethylpiperidine-oxyl (TEMPO)-anion complex to catalyze the decomposition of MgO. It was determined that this complex was capable of chemically decomposing MgO at 60 degrees C. A catalytic cycle for the realization of a rechargeable Mg-O2 electrode was designed by combining the decomposition of MgO via the TEMPO-anion complex and the TEMPO-redox couple. This work also demonstrates that a nonaqueous Mg-O2 battery incorporating acrylate polymer having TEMPO side units in the cathode shows evidence of being rechargeable. PMID- 26270362 TI - Molecular Simulation of the Transport of Drugs across Model Membranes. AB - This Perspective describes recent progress in the area of the molecular simulation of the interactions of hydrophobic and hydrophilic solutes with membranes. The ability to predict drug solubility prior to synthesis is an extremely desirable goal for pharmaceutical research. A major advantage of molecular dynamics is the ability to computationally probe both the drug solubility as well as the pathway for the transport of drugs across membranes. Computational methods to predict the interaction free energy of solutes with membranes have advanced significantly in recent years and can characterize the intra- and intermolecular state of the drug as well as perturbations of the drug to the membrane environment itself. In addition to a brief review on computational methods to characterize the transport of drugs across membranes, we will highlight recent discoveries and discuss the challenges and opportunities in the field. PMID- 26270361 TI - Lipid Peroxidation in Membranes: The Peroxyl Radical Does Not "Float". AB - Lipid peroxidation is a fundamental phenomenon in biology and medicine involved in a wide range of diseases. Some key microscopic aspects of this reaction in cell membranes are still poorly studied. In particular, it is commonly accepted that the propagation of the radical reaction in lipid bilayers is hampered by the rapid diffusion of peroxyl intermediates toward the water interface, that is, out of the reaction region. We investigated the validity of this "floating peroxyl radical" hypothesis by means of molecular modeling. Combining quantum calculations of model systems and atomistic simulations of lipid bilayers containing lipid oxidation products, we show that the peroxyl radical does not "float" at the surface of the membrane. Instead, it remains located quite deep inside the bilayer. In light of our findings, several critical aspects of biological membranes' peroxidation, such as their protection mechanisms, need to be revisited. Our data moreover help in the design of more efficient antioxidants, localized within reach of the reaction propagating radical. PMID- 26270363 TI - Multiple Electron Ejection from Proteins Resulting from Single-Photon Excitation in the Valence Shell. AB - One-photon multiple ionization is a signature of dynamical electron correlations in atoms and small molecules, as observed in the Auger process when Auger electron emission follows core-shell ionization. In such a process, the high energy needed to remove several electrons is due to the strong Coulombic attraction between the last departing electron(s) and the ionic core. Multiply negatively charged molecules offer the possibility to overcome the Coulombic attraction, opening the way for multielectron photodetachment following valence shell excitation. Here photodetachment studies have been performed on electrosprayed protein polyanions using vacuum ultraviolet synchrotron radiation coupled to a radiofrequency ion trap. Double, triple, and quadruple electron emissions from protein polyanions resulting from single-photon excitation in the valence shell were observed with ionization thresholds below 20 eV photon energy. This suggests the existence of large electronic correlations in proteins between weakly bound electrons standing on distant sites. Besides, the resulting multiradical polyanions appear to be remarkably stable, an important issue in radiobiology. PMID- 26270364 TI - Capturing CO2 in Monoethanolamine (MEA) Aqueous Solutions: Fingerprints of Carbamate Formation Assessed with First-Principles Simulations. AB - Chemical absorption in amine aqueous solutions is a widespread technology for postcombustion carbon capture, and a large effort is ongoing to improve their performance. Characterization of the "reactant" and "product" solutions at the microscopic level is highly desirable for process optimization. Recently X-ray scattering experiments and "in situ" infrared spectroscopy have been applied to this aim, but a complete and convincing interpretation is missing. We present large-scale ab initio molecular dynamics simulations of monoethanolamine solutions at experimental concentration and temperature and analyze how structural and vibrational properties change after carbamate formation. An exhaustive account of the experimental data is obtained. Fingerprints of the reaction products and specific interactions are unravelled. Hydration effects are specific to each component of the solution and are essential for a correct assignment of the experimental data. PMID- 26270365 TI - Correction to "Key Role of Frustration in Suppression of Magnetization Blocking in Single-Molecule Magnets". PMID- 26270366 TI - Metal/Phthalocyanine Hybrid Interface States on Ag(111). AB - A phthalocyanine/Ag(111) interface state is observed for the first time using time- and angle-resolved two-photon photoemission. For monolayer films of metal free (H2Pc) and iron phthalocyanine (FePc) on Ag(111), the state exists 0.23 +/- 0.03 and 0.31 +/- 0.03 eV above the Fermi level, respectively. Angle-resolved spectra show the state to be highly dispersive with an effective mass of 0.50 +/- 0.15 me for H2Pc and 0.67 +/- 0.14 me for FePc. Density functional theory calculations on the H2Pc/Ag(111) surface allow us to characterize this state as being a hybrid state resulting from the interaction between the unoccupied molecular states of the phthalocyanine ligand and the Shockley surface state present on the bare Ag(111) surface. This work, when taken together with the extensive literature on the 3,4,9,10-perylene tetracarboxylic dianhydride/Ag interface state, provides compelling evidence that the hybridization of metal surface states with molecular electronic states is a general phenomenon. PMID- 26270367 TI - Excitation Wavelength Dependence of the Dynamics of Bimolecular Photoinduced Electron Transfer Reactions. AB - The dynamics of photoinduced electron transfer between polar acceptors and donors has been investigated in apolar solvents using femtosecond-resolved fluorescence spectroscopy. It was found to be ultrafast and to continuously accelerate by varying the excitation wavelength from the maximum to the red edge of the absorption band of the acceptor, the overall difference being as large as a factor 4-5. This violation of the Kasha-Vavilov rule is explained by a correlation between the composition of the acceptor environment and its transition energy, that is, the more donors around an acceptor, the longer its absorption wavelength, and the faster the quenching. Because of preferential solvation, this dependence is already observed at low quencher concentrations. This effect, which requires quenching to be faster than the fluctuations of the environment composition, should be quite general for photoinduced charge transfer processes in low-polarity, viscous, or rigid media, such as those used in organic optoelectronic devices. PMID- 26270368 TI - Designing Bioinspired Artificial Cilia to Regulate Particle-Surface Interactions. AB - Biological cilia play a critical role in a stunning array of vital functions, from enabling marine organisms to trap food and expel fouling agents to facilitating the effective transport of egg cells in mammals. Inspired by the performance of these microscopic, hair-like filaments, researchers are synthesizing artificial cilia for use in lab-on-a-chip devices. There have, however, been few attempts to harness the artificial cilia to regulate the movement of particulates in these devices. Here, we review recent computational studies on the interactions between actuated artificial cilia and microscopic particles, showing that these cilia are effective at transporting both rigid and deformable particles in microchannels. The findings also reveal that these beating filaments can be used to separate microparticles based on their size and stiffness. Importantly, these studies indicate that artificial cilia can be used to prevent fouling by a wide variety of agents because they can expel both passive particulates and active swimmers from the underlying surface. These results can help guide experimental efforts to fully exploit artificial cilia in controlling particle motion within fluid environments. PMID- 26270369 TI - Tuning Spatial Distribution of Surface Hydroxyls on a Metal-Supported Single Layer Silica. AB - Using scanning tunneling microscopy and infrared reflection absorption spectroscopy, we studied adsorption of water on a single-layer silicatene grown on Ru(0001). Surface hydroxylation occurs exclusively on defect sites, resulting in isolated silanols (Si-OH). By modifying the defect structure of the overlayer, we have provided a means of tuning spatial distribution of surface hydroxyls to fabricate periodic arrays of silanols on a metal-supported single-layer silicatene. We have visualized the surface hydroxyls directly with atomic resolution to determine their preferential adsorption sites, which involve Si at the junction nodes of three nonequivalent silica polygons. Our results open up the possibility of patterning surface hydroxyls via the engineering of nanometer scale defect sites, which may then serve as potential templates for supported active species on oxide surfaces. PMID- 26270370 TI - Termination of Solid-State Crystal Growth in Molecular Glasses by Fluidity. AB - Fast crystal growth can abruptly emerge as molecular liquids are cooled to become glasses, a phenomenon presently unknown for other materials. This glass-to crystal (GC) mode can cause crystallization rates orders of magnitude faster than those predicted by standard models. While GC growth is known for 12 systems, its features vary greatly with growth rates spanning a factor of 10(4). We report that the general condition for GC growth to exist is that liquid diffusion be slow relative to crystal growth according to D/u < 7 pm. This condition holds for all liquids exhibiting GC growth and suggests that the phenomenon is a solid state process terminated by fluidity. GC growth must solidify several molecular layers before rearrangement by diffusion. We propose that GC growth propagates by a nonequilibrium crystal/liquid interface 3 nm wide that solidifies by local mobility. These results explain the prevalence of GC growth among organic liquids and guide its discovery in other materials. PMID- 26270371 TI - Electronic and Quantum Transport Properties of Atomically Identified Si Point Defects in Graphene. AB - We report high-resolution scanning transmission electron microscopy images displaying a range of inclusions of isolated silicon atoms at the edges and inner zones of graphene layers. Whereas the incorporation of Si atoms to a graphene armchair edge involves no reconstruction of the neighboring carbon atoms, the inclusion of a Si atom to a zigzag graphene edge entails the formation of five membered carbon rings. In all the observed atomic edge terminations, a Si atom is found bridging two C atoms in a 2-fold coordinated configuration. The atomic scale observations are underpinned by first-principles calculations of the electronic and quantum transport properties of the structural anomalies. Experimental estimations of Si-doped graphene band gaps realized by means of transport measurements may be affected by a low doping rate of 2-fold coordinated Si atoms at the graphene edges, and 4-fold coordinated at inner zones due to the apparition of mobility gaps. PMID- 26270372 TI - Correction to "Crystal Structures, Optical Properties, and Effective Mass Tensors of CH3NH3PbX3 (X = I and Br) Phases Predicted from HSE06". PMID- 26270373 TI - Dynamics of Lithium Dendrite Growth and Inhibition: Pulse Charging Experiments and Monte Carlo Calculations. AB - Short-circuiting via dendrites compromises the reliability of Li-metal batteries. Dendrites ensue from instabilities inherent to electrodeposition that should be amenable to dynamic control. Here, we report that by charging a scaled coin-cell prototype with 1 ms pulses followed by 3 ms rest periods the average dendrite length is shortened ~2.5 times relative to those grown under continuous charging. Monte Carlo simulations dealing with Li(+) diffusion and electromigration reveal that experiments involving 20 ms pulses were ineffective because Li(+) migration in the strong electric fields converging to dendrite tips generates extended depleted layers that cannot be replenished by diffusion during rest periods. Because the application of pulses much shorter than the characteristic time tauc ~ O(~1 ms) for polarizing electric double layers in our system would approach DC charging, we suggest that dendrite propagation can be inhibited (albeit not suppressed) by pulse charging within appropriate frequency ranges. PMID- 26270374 TI - Characterization of Nonanuclear Europium and Gadolinium Complexes by Gas-Phase Luminescence Spectroscopy. AB - Gas-phase measurements using mass-spectrometric techniques allow determination of the luminescence properties of selected molecular systems with knowledge of their exact composition. Furthermore, isolated luminophores are unaffected by matrix effects like solvent interactions or crystal packing. As a result, the system complexity is reduced relative to the condensed phase and a direct comparison with theory is facilitated. Herein, we report the intrinsic luminescence properties of nonanuclear europium(III) and gadolinium(III) 9-hydroxyphenalen-1 one (HPLN)-hydroxo complexes. Luminescence spectra of [Eu9(PLN)16(OH)10](+) ions reveal an europium-centered emission dominated by a 4-fold split Eu(III) hypersensitive transition. The corresponding Gd(III) complex, [Gd9(PLN)16(OH)10](+), shows a broad emission from a ligand based triplet state with an onset of about 1000 wavenumbers in excess of the europium emission. As supported by photoluminescence lifetime measurements for both complexes, we deduce an efficient europium sensitization via PLN-based triplet states. The luminescence spectra of the complexes are discussed in terms of a square antiprismatic europium/gadolinium core structure as suggested by density functional computations. PMID- 26270375 TI - Transient Grating Photoluminescence Spectroscopy: An Ultrafast Method of Gating Broadband Spectra. AB - Ultrafast photoluminescence (PL) spectroscopy can cleanly resolve excited-state dynamics and coupling to the environment, however, there is a demand for new methods that combine broadband detection and low backgrounds. We present a new method, transient grating photoluminescence spectroscopy (TGPLS), that addresses this challenge by exploiting a focusing geometry where ultrafast broadband spectra are transiently diffracted away from the background PL. We show that TGPLS can resolve the complex spectral relaxation observed in conjugated polymer and oligomer solutions, with an essentially flat spectral response throughout the visible region and potentially beyond. The benefits we demonstrate using TGPLS could expand access to spectral information, particularly for other multichromophoric and heterogeneous materials where complex spectral relaxation is expected. PMID- 26270376 TI - Amphiphile Meets Amphiphile: Beyond the Polar-Apolar Dualism in Ionic Liquid/Alcohol Mixtures. AB - The mesoscopic morphology of binary mixtures of ethylammonium nitrate (EAN), the protic ionic liquid par excellence, and methanol is explored using neutron/X-ray diffraction and computational techniques. Both compounds are amphiphilic and characterized by an extended hydrogen bonding network: surprisingly, though macroscopically homogeneous, these mixtures turn out to be mesoscopically highly heterogeneous. Our study reveals that even in methanol-rich mixtures, a wide distribution of clusters exists where EAN preserves its bulk, sponge-like morphology. Accordingly methanol does not succeed in fully dissociating the ionic liquid that keeps on organizing in a bulk-like fashion. This behavior represents the premises to the more dramatic phenomenology observed with longer alcohols that eventually phase separate from EAN. These results challenge the commonly accepted polar and apolar moieties segregation in ionic liquids/molecular liquids mixtures and the current understanding of technologically relevant solvation processes. PMID- 26270377 TI - 2D Electronic Spectroscopy Reveals Excitonic Structure in the Baseplate of a Chlorosome. AB - In green photosynthetic bacteria, the chlorosome baseplate mediates excitation energy transfer from the interior of the light-harvesting chlorosome toward the reaction centers. However, the electronic states of the baseplate remain unexplored, hindering the mechanistic understanding of the baseplate as an excitation energy collector and mediator. Here we use two-dimensional spectroscopy to study the excited state structure and internal energy relaxation in the baseplate of green sulfur bacterium Chlorobaculum tepidum. We resolved an exciton system with four energy states, indicating that the organization of the pigments in the baseplate is more complex than was thought before and constitutes at least four bacteriochlorophyll molecules in a close contact. Based on the finding that the energy of the baseplate states is in the same range as in the adjacent Fenna-Matthews-Olson complex, we propose a "lateral" energy transfer pathway, where excitation energy can flow through the photosynthetic unit via all the states of individual complexes. PMID- 26270378 TI - Inorganic Hole Conducting Layers for Perovskite-Based Solar Cells. AB - Hybrid organic-inorganic semiconducting perovskite photovoltaic cells are usually coupled with organic hole conductors. Here, we report planar, inverse CH3NH3PbI3 xClx-based cells with inorganic hole conductors. Using electrodeposited NiO as hole conductor, we have achieved a power conversion efficiency of 7.3%. The maximum VOC obtained was 935 mV with an average VOC value being 785 mV. Preliminary results for similar cells using electrodeposited CuSCN as hole conductor resulted in devices up to 3.8% in efficiency. The ability to obtain promising cells using NiO and CuSCN expands the presently rather limited range of available hole conductors for perovskite cells. PMID- 26270379 TI - Excitonic Photoluminescence from Nanodisc States in Graphene Oxides. AB - The origin of near-infrared (NIR) luminescence from graphene oxide (GO) is investigated by photoluminescence (PL) excitation spectroscopy, time-resolved PL spectroscopy, and density functional theory based many body perturbation theories. The energy of experimentally observed NIR PL peak depends on the excitation energy, and the peak broadens with increasing excitation energy. It is found that the PL decay curves in time-resolved spectroscopy show build-up behavior at lower emission energies due to energy transfer between smaller to larger graphene nanodisc (GND) states embedded in GO. We demonstrate that the NIR PL originates from ensemble emission of GND states with a few nanometers in size. The theoretical calculations reveal the electronic and excitonic properties of individual GND states with various sizes, which accounts for the inhomogeneously broadened NIR PL. We further demonstrate that the electronic properties are highly sensitive to the protonation and deprotonation processes of GND states using both the experimental and theoretical approaches. PMID- 26270380 TI - Ultrafast Relaxation Dynamics in trans-1,3-Butadiene Studied by Time-Resolved Photoelectron Spectroscopy with High Harmonic Pulses. AB - In trans-1,3-butadiene, the ultrafast relaxation from the doubly excited state 2(1)Ag and the corresponding recovery of the ground state 1(1)Ag were observed simultaneously for the first time by time-resolved photoelectron spectroscopy (TRPES) using 29.5 eV high harmonic pulses. The fast recovery of 1(1)Ag shows that the following dissociation upon photoexcitation takes place after returning to the ground state. At 427 fs after photoexcitation, only the ionization energy from the C?C sigma bond was found to remain shifted. Accompanying theoretical calculations with an assumption of Koopmans' theorem show that the ionization energy of the C?C sigma bond is modulated by vibrational excitation of the antisymmetric C?C stretching mode. TRPES by high harmonics can probe the changes in the molecular structure sensitively. PMID- 26270381 TI - Relationship between Diffusion and Chemical Exchange in Mixtures of Carbon Dioxide and an Amine-Functionalized Ionic Liquid by High Field NMR and Kinetic Monte Carlo Simulations. AB - NMR exchange spectroscopy (EXSY) and NMR diffusion spectroscopy (PFG NMR) were applied in combination with kinetic Monte Carlo (MC) simulations to investigate self-diffusion in a mixture of carbon dioxide and an amine-functionalized ionic liquid under conditions of an exchange of carbon dioxide molecules between the reacted and unreacted states in the mixture. EXSY studies enabled residence times of carbon dioxide molecules to be obtained in the two states, whereas PFG NMR revealed time-dependent effective diffusivities for diffusion times comparable with and larger than the residence times. Analytical treatment of the PFG NMR attenuation curves as well as fitting of the PFG NMR effective diffusivities by KMC simulations enabled determination of diffusivities of carbon dioxide in the reacted and unreacted states. In contrast to carbon dioxide, the ion diffusivities were found to be diffusion time independent. PMID- 26270382 TI - Molecular Dynamics Simulations of Nucleic Acids. From Tetranucleotides to the Ribosome. AB - We present a brief overview of explicit solvent molecular dynamics (MD) simulations of nucleic acids. We explain physical chemistry limitations of the simulations, namely, the molecular mechanics (MM) force field (FF) approximation and limited time scale. Further, we discuss relations and differences between simulations and experiments, compare standard and enhanced sampling simulations, discuss the role of starting structures, comment on different versions of nucleic acid FFs, and relate MM computations with contemporary quantum chemistry. Despite its limitations, we show that MD is a powerful technique for studying the structural dynamics of nucleic acids with a fast growing potential that substantially complements experimental results and aids their interpretation. PMID- 26270383 TI - Simulations Pave the Way for Exploring New Frontiers in the Biological Sciences. PMID- 26270384 TI - Fabricating a Homogeneously Alloyed AuAg Shell on Au Nanorods to Achieve Strong, Stable, and Tunable Surface Plasmon Resonances. AB - Colloidal metal nanocrystals with strong, stable, and tunable localized surface plasmon resonances (SPRs) can be useful in a corrosive environment for many applications including field-enhanced spectroscopies, plasmon-mediated catalysis, etc. Here, a new synthetic strategy is reported that enables the epitaxial growth of a homogeneously alloyed AuAg shell on Au nanorod seeds, circumventing the phase segregation of Au and Ag encountered in conventional synthesis. The resulting core-shell structured bimetallic nanorods (AuNR@AuAg) have well-mixed Au and Ag atoms in their shell without discernible domains. This degree of mixing allows AuNR@AuAg to combine the high stability of Au with the superior plasmonic activity of Ag, thus outperforming seemingly similar nanostructures with monometallic shells (e.g., Ag-coated Au NRs (AuNR@Ag) and Au-coated Au NRs (AuNR@Au)). AuNR@AuAg is comparable to AuNR@Ag in plasmonic activity, but that it is markedly more stable toward oxidative treatment. Specifically, AuNR@AuAg and AuNR@Ag exhibit similarly strong signals in surface-enhanced Raman spectroscopy that are some 30-fold higher than that of AuNR@Au. When incubated with a H(2)O(2) solution (0.5 m), the plasmonic activity of AuNR@Ag immediately and severely decayed, whereas AuNR@AuAg retained its activity intact. Moreover, the longitudinal SPR frequency of AuNR@AuAg can be tuned throughout the red wavelengths (~620-690 nm) by controlling the thickness of the AuAg alloy shell. The synthetic strategy is versatile to fabricate AuAg alloyed shells on different shaped Au, with prospects for new possibilities in the synthesis and application of plasmonic nanocrystals. PMID- 26270385 TI - Sexual Harassment, Bullying, and School Outcomes for High School Girls and Boys. AB - A comparison of the impact of bullying and sexual harassment on five school outcomes was conducted on a sample of high school students. Results revealed that sexual harassment was a stronger predictor than bullying of all school outcomes for both sexes, but especially for girls. This study suggests that sexual harassment, which activates sexist and heterosexist stereotypes, erodes school engagement, alienates students from teachers, and adversely affects academic achievement, to a greater degree than bullying does. PMID- 26270386 TI - Predicting Abused Women With Children Who Return to a Shelter: Development and Use of a Rapid Assessment Triage Tool. AB - To develop a tool to predict risk for return to a shelter, 150 women with children, exiting a domestic violence shelter, were evaluated every 4 months for 24 months to determine risk factors for returning to a shelter. The study identified four risk factors, including danger for murder, woman's age (i.e., older women), tangible support (i.e., access to money, transportation), and child witness to verbal abuse of the mother. An easy to use, quick triage tool with a weighted score was derived, which can identify with 90% accuracy abused women with children most likely to return to shelters. PMID- 26270387 TI - Bringing a Network-Oriented Approach to Domestic Violence Services: A Focus Group Exploration of Promising Practices. AB - Despite powerful evidence that informal social support contributes to survivors' safety and well-being, mainstream domestic violence (DV) programs have not developed comprehensive models for helping isolated survivors re-engage with these networks. Although many advocates use network-oriented strategies informally, they often do so without resources, funding, or training. This qualitative focus group study explored advocates' use and perceptions of network oriented strategies. Advocates working in a range of DV programs across one state described the importance of network-oriented work and articulated its five dimensions, including helping survivors build their capacity to form healthy relationships, identify helpful and harmful network members, re-engage with existing networks, develop new relationships, and respond more effectively to network members. PMID- 26270388 TI - Two Pseudopolymorphic Star-Shaped Tetranuclear Co(3+) Compounds with Disulfide Anions Exhibiting Two Different Connection Modes and Promising Photocatalytic Properties. AB - The compound [Co4(C6H14N2)4(MU4-S2)2(MU2-S2)4] (I) and the pseudo-polymorph [Co4(C6H14N2)4(MU4-S2)2(MU2-S2)4]?4 H2O (II) were obtained under solvothermal conditions (C6H14N2=trans-1,2-diaminocyclohexane). The structures feature S2(2-) ions exhibiting two different coordination modes. Terminal S2(2-) entities join two Co(3+) centres in a MU2 fashion, whereas the central S2(2-) groups connect four Co(3+) cations in a MU4-coordination mode. Compound II can be transformed into compound I by heat and storage over P2O5 and storing compound I in humid air yields in the formation of compound II. The intermolecular interactions investigated through Hirshfeld surface analysis reveal that besides S???H bonding close contacts are associated with relatively weak H???H interactions. A detailed DFT analysis of the bonding situation explains the long S-S bonds in the MU4 bridging S2(2-) units and the short bonds for the S2(2-) moieties in the MU2 connecting mode. Photocatalytic hydrogen evolution experiments demonstrate the potential of compound II as catalyst. PMID- 26270390 TI - Transformative Nature of Global Partnerships. PMID- 26270389 TI - Predictive value of factor VIII levels for recurrent venous thrombosis: results from the MEGA follow-up study. AB - BACKGROUND: Prediction of recurrent venous thrombosis remains a challenge in the clinic. OBJECTIVE: To investigate the predictive value of coagulation factor VIII (FVIII) levels for recurrent venous thrombosis. PATIENTS/METHODS: Patients, aged 18-70 years with a first venous thrombosis, were followed from discontinuation of anticoagulant treatment (1999-2010 MEGA follow-up study). The levels of FVIII activity, FVIII antigen and von Willebrand factor (VWF) antigen were measured at least 3 months after cessation of anticoagulant treatment. RESULTS: Of 2242 patients followed for a median of 6.9 years, 343 developed recurrent thrombosis (incidence rate 2.7/100 patient-years; 95% confidence interval [CI] 2.5-3.1). Recurrence rates steadily increased with higher FVIII activity levels, from 1.4 (95% CI 1.0-1.9), 2.3 (95% CI 1.8-2.9), 3.0 (95% CI 2.4-3.7), 3.2 (95% CI 2.5 4.1), 3.9 (95% CI 2.8-5.3) to 5.1 (95% CI 3.8-6.8) per 100 patient-years, for levels ranging from < 100 IU dL(-1) to > 200 IU dL(-1) . Patients in the highest category of FVIII (> 200 IU dL(-1) ) had a three-fold higher recurrence rate than patients in the lowest category (<= 100 IU dL(-1) ) (hazard ratio 3.4; 95% CI 2.2 5.3). Results were similar for FVIII antigen and VWF antigen levels, in several sensitivity analyses, and FVIII predicted recurrence rates over a long time period. Within subgroups of patients currently assumed to have low recurrence risks, a high level of FVIII was still predictive for recurrences. Adding FVIII to an existing prediction model (DASH score) improved its predictive value, and, after replacement of D-dimer with FVIII, the model performed equally well, if not better. CONCLUSIONS: FVIII predicted recurrence in a dose-response fashion, overall and in several subgroups, and is a strong candidate component of recurrence prediction tools. PMID- 26270391 TI - Stereoselective Synthesis of (2Z)-2,4-Dienamides via NBS-Mediated Allyloxyl Addition-Claisen Rearrangement-Dehydrobromination Cascade Reaction of Ynsulfonamides. AB - An NBS-promoted allyloxyl addition-Claisen rearrangement-dehydrobromination cascade reaction has been developed. More than 20 substituted alkynylsulfonamides were reacted with allyl alcohols to generate (2Z)-2,4-dienamides in moderate to high yields. A mechanistic model has been proposed to account for the overall reaction sequence including the stereochemical outcome. Theoretical calculations suggested that a [3,3] sigmatropic rearrangement be the rate-limiting step. PMID- 26270392 TI - A Versatile Strategy for Shish-Kebab-like Multi-heterostructured Chalcogenides and Enhanced Photocatalytic Hydrogen Evolution. AB - A series of multi-heterostructured metal chalcogenides (CdS-Te, NiS/CdS-Te, and MoS2/CdS-Te) with a surprising shish-kebab-like structure have been synthesized via a one-step microwave-assisted pyrolysis of dithiocarbamate precursors in ethylene glycol. Subsequently, CdS-Te composites were exploited as a self sacrificial template to craft various CdS-Te@(Pt, Pd) multi-heterostructures. Highly uniform dispersion and intimate interactions between CdS and multicomponent cocatalysts, together with improved separation of photogenerated carriers due to the presence of Te nanotubes (NTs) and trace CdTe, enable CdS based heterostructured photocatalysts to exhibit greatly enhanced efficiency and stability in the photocatalytic production of H2. Thorough morphological characterizations revealed that the growth of metal sulfide/Te heterostructures originates from the growth of Te tubes, which is likely governed by diffusion limited depletion of the Te precursor and the dissolution-crystallization process of Te seeds followed by the formation of metal sulfide kebabs. PMID- 26270393 TI - The PURE system for the cell-free synthesis of membrane proteins. AB - Cell-free gene expression systems are biotechnological tools for the in vitro production of proteins of interest. The addition of membrane vesicles (liposomes) enables the production of membrane proteins, including those in large-molecular weight complexes, such as the SecYEG translocon or ATP synthase. Here we describe a protocol for the cell-free synthesis of membrane proteins using the protein synthesis using recombinant elements (PURE) system, and for subsequent quantification of products and analyses of membrane localization efficiency, product orientation in the membrane and complex formation in the membrane. In addition, measurements of ATP synthase activity are used as an example to demonstrate the functional nature of the cell-free synthesized proteins. This protocol allows the rapid production and the detailed analysis of membrane proteins, and the complete process from template DNA preparation to activity measurement can be accomplished within 1 d. In contrast to alternative methods using living cells, this protocol can also help to prevent the difficulties in membrane protein purification and the risks of protein aggregation during reconstitution into lipid membranes. PMID- 26270394 TI - Cardiac differentiation of human pluripotent stem cells in scalable suspension culture. AB - Cardiomyocytes (CMs) generated from human pluripotent stem cells (hPSCs) are a potential cell source for regenerative therapies, drug discovery and disease modeling. All these applications require a routine supply of relatively large quantities of in vitro-generated CMs. This protocol describes a suspension culture-based strategy for the generation of hPSC-CMs as cell-only aggregates, which facilitates process development and scale-up. Aggregates are formed for 4 d in hPSC culture medium followed by 10 d of directed differentiation by applying chemical Wnt pathway modulators. The protocol is applicable to static multiwell formats supporting fast adaptation to specific hPSC line requirements. We also demonstrate how to apply the protocol using stirred tank bioreactors at a 100-ml scale, providing a well-controlled upscaling platform for CM production. In bioreactors, the generation of 40-50 million CMs per differentiation batch at >80% purity without further lineage enrichment can been achieved within 24 d. PMID- 26270395 TI - In vitro bioengineered model of cortical brain tissue. AB - A bioengineered model of 3D brain-like tissue was developed using silk-collagen protein scaffolds seeded with primary cortical neurons. The scaffold design provides compartmentalized control for spatial separation of neuronal cell bodies and neural projections, which resembles the layered structure of the brain (cerebral cortex). Neurons seeded in a donut-shaped porous silk sponge grow robust neuronal projections within a collagen-filled central region, generating 3D neural networks with structural and functional connectivity. The silk scaffold preserves the mechanical stability of the engineered tissues, allowing for ease of handling, long-term culture in vitro and anchoring of the central collagen gel to avoid shrinkage, and enabling neural network maturation. This protocol describes the preparation and manipulation of silk-collagen constructs, including the isolation and seeding of primary rat cortical neurons. This 3D technique is useful for mechanical injury studies and as a drug screening tool, and it could serve as a foundation for brain-related disease models. The protocol of construct assembly takes 2 d, and the resulting tissues can be maintained in culture for several weeks. PMID- 26270397 TI - Validated method for the quantification of free and total carnitine, butyrobetaine, and acylcarnitines in biological samples. AB - A validated quantitative method for the determination of free and total carnitine, butyrobetaine, and acylcarnitines is presented. The versatile method has four components: (1) isolation using strong cation-exchange solid-phase extraction, (2) derivatization with pentafluorophenacyl trifluoromethanesulfonate, (3) sequential ion-exchange/reversed-phase (ultra) high-performance liquid chromatography [(U)HPLC] using a strong cation-exchange trap in series with a fused-core HPLC column, and (4) detection with electrospray ionization multiple reaction monitoring (MRM) mass spectrometry (MS). Standardized carnitine along with 65 synthesized, standardized acylcarnitines (including short-chain, medium-chain, long-chain, dicarboxylic, hydroxylated, and unsaturated acyl moieties) were used to construct multiple-point calibration curves, resulting in accurate and precise quantification. Separation of the 65 acylcarnitines was accomplished in a single chromatogram in as little as 14 min. Validation studies were performed showing a high level of accuracy, precision, and reproducibility. The method provides capabilities unavailable by tandem MS procedures, making it an ideal approach for confirmation of newborn screening results and for clinical and basic research projects, including treatment protocol studies, acylcarnitine biomarker studies, and metabolite studies using plasma, urine, tissue, or other sample matrixes. PMID- 26270396 TI - Practice Patterns and Outcomes of Treatments for Atrial Fibrillation During Sepsis: A Propensity-Matched Cohort Study. AB - BACKGROUND: Atrial fibrillation (AF) during sepsis is associated with increased morbidity and mortality, but practice patterns and outcomes associated with rate- and rhythm-targeted treatments for AF during sepsis are unclear. METHODS: This was a retrospective cohort study using enhanced billing data from approximately 20% of United States hospitals. We identified factors associated with IV AF treatments (?-blockers [BBs], calcium channel blockers [CCBs], digoxin, or amiodarone) during sepsis. We used propensity score matching and instrumental variable approaches to compare mortality between AF treatments. RESULTS: Among 39,693 patients with AF during sepsis, mean age was 77 +/- 11 years, 49% were women, and 76% were white. CCBs were the most commonly selected initial AF treatment during sepsis (14,202 patients [36%]), followed by BBs (11,290 [28%]), digoxin (7,937 [20%]), and amiodarone (6,264 [16%]). Initial AF treatment selection differed according to geographic location, hospital teaching status, and physician specialty. In propensity-matched analyses, BBs were associated with lower hospital mortality when compared with CCBs (n = 18,720; relative risk [RR], 0.92; 95% CI, 0.86-0.97), digoxin (n = 13,994; RR, 0.79; 95% CI, 0.75-0.85), and amiodarone (n = 5,378; RR, 0.64; 95% CI, 0.61-0.69). Instrumental variable analysis showed similar results (adjusted RR fifth quintile vs first quintile of hospital BB use rate, 0.67; 95% CI, 0.58-0.79). Results were similar among subgroups with new-onset or preexisting AF, heart failure, vasopressor-dependent shock, or hypertension. CONCLUSIONS: Although CCBs were the most frequently used IV medications for AF during sepsis, BBs were associated with superior clinical outcomes in all subgroups analyzed. Our findings provide rationale for clinical trials comparing the effectiveness of AF rate- and rhythm-targeted treatments during sepsis. PMID- 26270398 TI - A combined cheminformatic and bioinformatic approach to address the proteolytic stability challenge in peptide-based drug discovery. AB - We have created models to predict cleavage sites for several human proteases including caspase-1, caspase-3, caspase-6, caspase-7, cathepsin B, cathepsin D, cathepsin G, cathepsin K, cathepsin L, elastase-2, granzyme A, granzyme B, matrix metallopeptidase-2 (MMP2), MMP7, MMP9, thrombin, and trypsin-1. Rather than representing the sequence pattern around the potential cleavage site through a series of flags with each flag representing one of the 20 standard amino acids, we first represent each amino acid by its calculated properties. For these calculated properties, we use validated cheminformatic descriptors, such as molecular weight, logP, and polar surface area, of the individual amino acids. Finally, the cleavage site-specific descriptors are calculated through various combinations of the individual amino acid descriptors for the residues surrounding the cleavage site. Some of these combinations do not take into account the location of the residue, as long as it is in a prescribed neighborhood of the potential cleavage site, whereas others are sensitive to the precise order of the residues in the sequence. The key advantage of this approach is that it allows one to perform meaningful calculations with nonstandard amino acids for which little or no data exists. Finally, using both docking and molecular dynamics simulations, we examine the potential for and limitations of protease crystal structures to impact the design of proteolytically stable peptides. PMID- 26270401 TI - Can Ophthalmologists Achieve Better Blood Glucose Control in Their Diabetic Patients? PMID- 26270402 TI - Lower Eyelid Lesion. PMID- 26270404 TI - Error in Table. PMID- 26270403 TI - Bilateral Acute-Onset Vision Loss in a Previously Healthy Man. PMID- 26270405 TI - Posterior Segment Findings in X-Linked Chronic Granulomatous Disease. PMID- 26270406 TI - Vitreous Veils Associated With Congenital X-Linked Retinoschisis. PMID- 26270407 TI - Frontal Sinus Mucocele Diagnosed by Fundus Examination and B-Mode Ultrasonography. PMID- 26270408 TI - Epiretinal Membrane Demonstrated by Optical Coherence Tomography in a Patient With Retinal Cavernous Hemangioma. PMID- 26270409 TI - Usefulness of Multigene Testing: Catching the Train That's Left the Station. PMID- 26270410 TI - Construction and Functions of Cyclodextrin-Based 1D Supramolecular Strands and their Secondary Assemblies. AB - Cyclodextrins (CDs), a class of cyclic oligosaccharides, are water-soluble, nontoxic, and commercial available with a low price, and their well-defined hydrophobic cavity can bind various organic/biological substrates. Through their molecular assembly mediated by organic, inorganic, or polymeric molecules as templates, CDs and their functional derivatives can be assembled to 1D supramolecular strands, wherein the functional groups of the CDs are closely located in a highly ordered manner. This structural feature greatly favors the cooperative effect of numerous functional groups in the supramolecular strand, as well as the interactions of the supramolecular strands with the multiple binding sites of substrates, especially biological substrates. Therefore, CD-based 1D supramolecular strands exhibit many material, biological, and catalytic functions, and these properties can be further improved through their secondary assembly. An overview of recent advances in the development of the construction and functions of CD-based 1D supramolecular strands and their secondary assemblies is given here. It is expected that the representative contributions described can inspire future investigations and lead to discoveries that promote the research of CD-based functional materials. PMID- 26270411 TI - Posterior scleral bowing with choroidal nevus on enhanced-depth imaging optical coherence tomography. AB - IMPORTANCE: Recognition of posterior scleral bowing with choroidal nevus is essential to avoid an underestimation of tumor thickness. OBJECTIVE: To describe a particular observation of posterior scleral bowing associated with choroidal nevus on enhanced-depth imaging (EDI) optical coherence tomography (OCT). DESIGN, SETTING, AND PARTICIPANTS: Retrospective observational case series at a referral center involving 17 eyes of 17 patients. Patients were seen from June 2013 to July 2014, with all data collected and analyzed from June 2014 to July 2014. INTERVENTIONS: Retrospective medical record review and multimodal imaging including fundus photography, autofluorescence, infrared reflectance, ultrasonography, and EDI-OCT. MAIN OUTCOMES AND MEASURES: Clinical and imaging characteristics. RESULTS: Analysis of 318 consecutive patients with choroidal nevus imaged over a 1-year period revealed that 17 cases (5%) demonstrated the EDI-OCT feature of posterior scleral bowing. Of these 17 cases, the mean patient age was 58 years (median, 58 years; range, 36-75 years) and there were 6 men (35%) and 11 women (65%). The nevus was classified as pigmented (n = 3; 18%), nonpigmented (n = 2; 12%), and mixed pigmentation (n = 12; 71%), and with no surrounding halo (n = 7; 41%). Associated features included overlying drusen (n = 9; 53%), retinal pigment epithelial alterations (n = 9; 53%), subretinal fluid (n = 5; 29%), and orange pigment (n = 3; 18%). The nevus was clinically estimated to be of 4.91-mm basal dimension and measured ultrasonographically at 1.59-mm thickness. By EDI-OCT, the nevus mean thickness was 628 um (0.63 mm). All cases demonstrated posterior scleral bowing with mean scleral excavation of 398 um (median, 377 um; range, 134-739 um). Underlying the nevus, the scleral thickness was not measurable; however, at the nevus margin, the choroid and sclera appeared normal. Clinical features correlated with posterior scleral bowing included reduced distance to the optic disc (difference, 1.3 mm; 95% CI, -2.95 mm to 5.51 mm; P = .01) and the foveola (difference, 2.14 mm; 95% CI, 0.80 mm to 3.48 mm; P < .001), as well as the presence of surrounding halo (difference, 36%; 95% CI, 16.86% to 59.27%; P < .001). CONCLUSIONS AND RELEVANCE: Choroidal nevus can show focal posterior scleral bowing on EDI-OCT in 5% of cases. This finding was related to more posterior location of nevus, less/mixed pigmentation, and surrounding halo. This finding could lead to underestimation of tumor thickness as the tumor bows backward rather than forward. PMID- 26270413 TI - Reaction of Dilithio Reagents with PhSiH3: Formation of Siloles and 3 Silacyclopentenes. AB - The reaction chemistry between 1,4-dilithio-1,3-butadienes (dilithio reagents for short) and PhSiH3 has been investigated. Direct substitution of two hydride ions from PhSiH3 with the dilithio reagents led to multisubstituted siloles (silacyclopentadienes) in diethyl ether solution, with the concomitant generation of LiH. When THF was used as the solvent, the reaction between PhSiH3 and 1,4 bis(silyl) dilithio reagents afforded cis-3-silacyclopentenes stereoselectively. Experimental results demonstrated that reactive LiH was generated in situ in the reaction system. Formal syn addition of LiH to silacyclopentadiene intermediates would afford silacyclopentenes, most likely via pentavalent organosilicates. PMID- 26270412 TI - Synthesis and Magneto-Thermal Actuation of Iron Oxide Core-PNIPAM Shell Nanoparticles. AB - Superparamagnetic nanoparticles have been proposed for many applications in biotechnology and medicine. In this paper, it is demonstrated how the excellent colloidal stability and magnetic properties of monodisperse and individually densely grafted iron oxide nanoparticles can be used to manipulate reversibly the solubility of nanoparticles with a poly(N-isopropylacrylamide)nitrodopamine shell. "Grafting-to" and "grafting-from" methods for synthesis of an irreversibly anchored brush shell to monodisperse, oleic acid coated iron oxide cores are compared. Thereafter, it is shown that local heating by magnetic fields as well as global thermal heating can be used to efficiently and reversibly aggregate, magnetically extract nanoparticles from solution and spontaneously redisperse them. The coupling of magnetic and thermally responsive properties points to novel uses as smart materials, for example, in integrated devices for molecular separation and extraction. PMID- 26270414 TI - Correction to "Facile Preparative Route to Alkanethiolate-Coated Au38 Nanoparticles: Postsynthesis Core Size Evolution". PMID- 26270417 TI - Remembering that old dogs can still do tricks. PMID- 26270416 TI - Discovery of Potent and Selective RSK Inhibitors as Biological Probes. AB - While the p90 ribosomal S6 kinase (RSK) family has been implicated in multiple tumor cell functions, the full understanding of this kinase family has been restricted by the lack of highly selective inhibitors. A bis-phenol pyrazole was identified from high-throughput screening as an inhibitor of the N-terminal kinase of RSK2. Structure-based drug design using crystallography, conformational analysis, and scaffold morphing resulted in highly optimized difluorophenol pyridine inhibitors of the RSK kinase family as demonstrated cellularly by the inhibition of YB1 phosphorylation. These compounds provide for the first time in vitro tools with an improved selectivity and potency profile to examine the importance of RSK signaling in cancer cells and to fully evaluate RSK as a therapeutic target. PMID- 26270415 TI - What pulmonologists think about the asthma-COPD overlap syndrome. AB - BACKGROUND: Some patients with COPD may share characteristics of asthma; this is the so-called asthma-COPD overlap syndrome (ACOS). There are no universally accepted criteria for ACOS, and most treatments for asthma and COPD have not been adequately tested in this population. MATERIALS AND METHODS: We performed a survey among pulmonology specialists in asthma and COPD aimed at collecting their opinions about ACOS and their attitudes in regard to some case scenarios of ACOS patients. The participants answered a structured questionnaire and attended a face-to-face meeting with the Metaplan methodology to discuss different aspects of ACOS. RESULTS: A total of 26 pulmonologists with a mean age of 49.7 years participated in the survey (13 specialists in asthma and 13 in COPD). Among these, 84.6% recognized the existence of ACOS and stated that a mean of 12.6% of their patients might have this syndrome. In addition, 80.8% agreed that the diagnostic criteria for ACOS are not yet well defined. The most frequently mentioned characteristics of ACOS were a history of asthma (88.5%), significant smoking exposure (73.1%), and postbronchodilator forced expiratory volume in 1 second/forced vital capacity <0.7 (69.2%). The most accepted diagnostic criteria were eosinophilia in sputum (80.8%), a very positive bronchodilator test (69.2%), and a history of asthma before 40 years of age (65.4%). Up to 96.2% agreed that first-line treatment for ACOS was the combination of a long-acting beta2-agonist and inhaled steroid, with a long-acting antimuscarinic agent (triple therapy) for severe ACOS. CONCLUSION: Most Spanish specialists in asthma and COPD agree that ACOS exists, but the diagnostic criteria are not yet well defined. A previous history of asthma, smoking, and not fully reversible airflow limitation are considered the main characteristics of ACOS, with the most accepted first-line treatment being long-acting beta2-agonist/inhaled corticosteroids. PMID- 26270418 TI - To the Editor: Eruptive xanthoma. PMID- 26270419 TI - In Reply: Eruptive xanthoma. PMID- 26270420 TI - To the Editor: Risk of falls. PMID- 26270421 TI - In Reply: Risk of falls. PMID- 26270422 TI - To the Editor: The role of sentinel lymph node biopsy after excision of melanomas. PMID- 26270423 TI - In Reply: The role of sentinel lymph node biopsy after excision of melanomas. PMID- 26270424 TI - Parvovirus mimicking acute HIV infection. PMID- 26270425 TI - Respiratory artifact: A second vital sign on the electrocardiogram. PMID- 26270426 TI - Does stenting of severe renal artery stenosis improve outcomes compared with medical therapy alone? PMID- 26270427 TI - Stenting may benefit select patients with severe renal artery stenosis. PMID- 26270428 TI - Geriatrics update 2015: Vaccination, frailty, chronic disease guidelines, and cognition. AB - This paper discusses recent developments and recommendations for elderly patients concerning immunizations, heart failure, lipid therapy, blood pressure control, and dementia. PMID- 26270429 TI - Universal precautions to reduce stimulant misuse in treating adult ADHD. AB - In the United States, stimulants remain the approved pharmacotherapy of choice for adults with attention-deficit/hyperactivity disorder (ADHD). Many patients respond to these drugs, but stimulants also have a significant potential for misuse. This article suggests the "universal precautions" approach to reducing these risks while promoting appropriate medication use. PMID- 26270430 TI - Starting insulin in patients with type 2 diabetes: An individualized approach. AB - Because type 2 diabetes mellitus is a progressive disease, most patients eventually need insulin. When and how to start insulin therapy are not one-size fits-all decisions but rather must be individualized. This paper reviews the indications, goals, and options for insulin therapy in type 2 diabetes. PMID- 26270431 TI - E-cigarettes: Safe to recommend to patients? AB - Electronic cigarettes (e-cigarettes)--devices that generate a nicotine vapor that can be inhaled by the user in a fashion that mimics the experience of smoking- are increasing in popularity, and many people seem to view them as reasonable alternatives to nicotine replacement therapy to help them refrain from smoking. Physicians should not encourage such a view. E-cigarettes are unregulated nicotine delivery systems that have never been subjected to any kind of testing of safety or of efficacy as nicotine replacement therapy. Moreover, for young people who have never smoked, these devices could potentially serve as a gateway drug. PMID- 26270432 TI - Diuretics for hypertension: Hydrochlorothiazide or chlorthalidone? AB - Thiazide diuretics are the cornerstone of treatment of hypertension in most patients. Hydrochlorothiazide is the most commonly used thiazide diuretic in the United States, but interest in chlorthalidone is increasing. The authors summarize the literature comparing these two agents. PMID- 26270433 TI - Comprehensive wound malodor management: Win the RACE. AB - Complex wounds that give off a foul odor are common in various patient care settings. Wound malodor has grave effects, both physical and psychological, and its management presents a serious challenge for caregivers. Multiple factors and processes involved in malodor production need to be considered in designing a comprehensive treatment plan described by the acronym RACE: removal of necrotic tissue, antibacterials, odor concealers, and education and support. Improving quality of life is the outcome of winning the RACE against malodor. PMID- 26270434 TI - Treatment for women with postpartum iron deficiency anaemia. AB - BACKGROUND: Postpartum iron deficiency anaemia is caused by bleeding or inadequate dietary iron intake/uptake. This condition is defined by iron deficiency accompanied by a lower than normal blood haemoglobin concentration, although this can be affected by factors other than anaemia and must be interpreted in the light of any concurrent symptoms. Symptoms include fatigue, breathlessness, and dizziness. Treatment options include oral or intravenous iron, erythropoietin which stimulates red blood cell production, and substitution by red blood cell transfusion. OBJECTIVES: To assess the efficacy and harms of the available treatment modalities for women with postpartum iron deficiency anaemia. SEARCH METHODS: The Cochrane Pregnancy and Childbirth Group's Trials Register (9 April 2015); the WHO International Clinical Trials Registry Portal (ICTRP), and the Latin-American and Caribbean Health Sciences Literature database (LILACS) (8 April 2015) and reference lists of retrieved studies. SELECTION CRITERIA: We included published, unpublished and ongoing randomised controlled trials that compared a treatment for postpartum iron deficiency anaemia with placebo, no treatment, or another treatment for postpartum iron deficiency anaemia, including trials described in abstracts only. Cluster-randomised trials were eligible for inclusion. We included both open-label trials and blinded trials, regardless of who was blinded. The participants were women with a postpartum haemoglobin of 120 g per litre (g/L) or less, for which treatment was initiated within six weeks after childbirth.Non-randomised trials, quasi randomised trials and trials using a cross-over design were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, quality, and extracted data. We contacted study authors and pharmaceutical companies for additional information. MAIN RESULTS: We included 22 randomised controlled trials (2858 women), most of which had high risk of bias in several domains. We performed 13 comparisons. Many comparisons are based on a small number of studies with small sample sizes. No analysis of our primary outcomes contained more than two studies.Intravenous iron was compared to oral iron in 10 studies (1553 women). Fatigue was reported in two studies and improved significantly favouring the intravenously treated group in one of the studies. Other anaemia symptoms were not reported. One woman died from cardiomyopathy (risk ratio (RR) 2.95; 95% confidence interval (CI) 0.12 to 71.96; two studies; one event; 374 women; low quality evidence). One woman developed arrhythmia. Both cardiac complications occurred in the intravenously treated group. Allergic reactions occurred in three women treated with intravenous iron, not statistically significant (average RR 2.78; 95% CI 0.31 to 24.92; eight studies; 1454 women; I2 = 0%; low quality evidence). Gastrointestinal events were less frequent in the intravenously treated group (average RR 0.31; 95% CI 0.20 to 0.47; eight studies; 169 events; 1307 women; I2 = 0%; very low quality evidence).One study evaluated red blood cell transfusion versus non-intervention. General fatigue improved significantly more in the transfusion group at three days (MD -0.80; 95% CI -1.53 to -0.07; women 388; low quality evidence), but no difference between groups was seen at six weeks. Maternal mortality was not reported.The remaining comparisons evaluated oral iron (with or without other food substances) versus placebo (three studies), intravenous iron with oral iron versus oral iron (two studies) and erythropoietin (alone or combined with iron) versus placebo or iron (seven studies). These studies did not investigate fatigue. Maternal mortality was rarely reported. AUTHORS' CONCLUSIONS: The body of evidence did not allow us to reach a clear conclusion regarding the efficacy of the interventions on postpartum iron deficiency anaemia. The quality of evidence was low.Clinical outcomes were rarely reported. Laboratory values may not be reliable indicators for efficacy, as they do not always correlate with clinical treatment effects. It remains unclear which treatment modality is most effective in alleviating symptoms of postpartum anaemia.Intravenous iron was superior regarding gastrointestinal harms, however anaphylaxis and cardiac events occurred and more data are needed to establish whether this was caused by intravenous iron.The clinical significance of some temporarily improved fatigue scores in women treated with blood transfusion is uncertain and this modest effect should be balanced against known risks, e.g. maternal mortality (not reported) and maternal immunological sensitisation, which can potentially harm future pregnancies.When comparing oral iron to placebo it remains unknown whether efficacy (relief of anaemia symptoms) outweighs the documented gastrointestinal harms.We could not draw conclusions regarding erythropoietin treatment due to lack of evidence.Further research should evaluate treatment effect through clinical outcomes, i.e. presence and severity of anaemia symptoms balanced against harms, i.e. survival and severe morbidity. PMID- 26270435 TI - Intramolecular Cross-Linking Methodologies for the Synthesis of Polymer Nanoparticles. PMID- 26270436 TI - Prospecting Lighting Applications with Ligand Field Tools and Density Functional Theory: A First-Principles Account of the 4f(7)-4f(6)5d(1) Luminescence of CsMgBr3:Eu(2+). AB - The most efficient way to provide domestic lighting nowadays is by light-emitting diodes (LEDs) technology combined with phosphors shifting the blue and UV emission toward a desirable sunlight spectrum. A route in the quest for warm white light goes toward the discovery and tuning of the lanthanide-based phosphors, a difficult task, in experimental and technical respects. A proper theoretical approach, which is also complicated at the conceptual level and in computing efforts, is however a profitable complement, offering valuable structure-property rationale as a guideline in the search of the best materials. The Eu(2+)-based systems are the prototypes for ideal phosphors, exhibiting a wide range of visible light emission. Using the ligand field concepts in conjunction with density functional theory (DFT), conducted in nonroutine manner, we develop a nonempirical procedure to investigate the 4f(7)-4f(6)5d(1) luminescence of Eu(2+) in the environment of arbitrary ligands, applied here on the CsMgBr3:Eu(2+)-doped material. Providing a salient methodology for the extraction of the relevant ligand field and related parameters from DFT calculations and encompassing the bottleneck of handling large matrices in a model Hamiltonian based on the whole set of 33,462 states, we obtained an excellent match with the experimental spectrum, from first-principles, without any fit or adjustment. This proves that the ligand field density functional theory methodology can be used in the assessment of new materials and rational property design. PMID- 26270437 TI - Use of prescription drugs is common during pregnancy, US study finds. PMID- 26270438 TI - Correction to: Regression to the mean: what it is and how to deal with it. PMID- 26270439 TI - Electric impedance platelet aggregometry in cardiac surgery patients: A comparative study of two technologies. AB - Platelet function tests are suggested to assess platelet reactivity before cardiac and major non-cardiac surgery. Different point-of-care platelet function tests are available. Among these, electric impedance platelet aggregometry (EIPA) (Multiplate(r), MP) is one of the most widely used techniques. Recently, a new EIPA system (Rotem Platelet(r), RP) was released. This is a comparative study of platelet function measured with MP and RP. Fifty cardiac surgery patients were admitted to this study. All the patients received a preoperative platelet function test with both the MP and the RP; for each technology, two tests were performed: the ADPtest (investigating P2Y12 receptor platelet reactivity) and the TRAPtest (investigating the thrombin-dependent platelet reactivity). ADP-based platelet reactivity values demonstrated a significant (p = 0.019) correlation between the MP and the RP; and a marginally significant (p = 0.042) correlation for TRAP-based tests. The Bland-Altman analysis of the ADPtest demonstrated a positive bias of 5.94 units (MP > RP) and a percentage error of 88%. For the TRAPtest, there was a positive bias of 12 units (MP > RP) and a percentage error of 89%. In patients who were preoperatively treated with P2Y12 receptor inhibitors, only the MP ADPtest was positively associated with the days from drug discontinuation (p = 0.003). Platelet function assessment with RP greatly differs from the equivalent MP measure, and no correction value can be applied due to the low level of precision. This applies both to ADPtest and TRAPtest. The MP ADPtest is more reliable for platelet reactivity after discontinuation of P2Y12 receptor inhibitors. PMID- 26270440 TI - Fractionated Radiation Therapy for Benign Nonacoustic Schwannomas. AB - OBJECTIVES: We analyzed the outcomes of patients with benign nonacoustic schwannomas treated with fractionated radiation therapy (RT). METHODS: Between October 1987 and March 2013, 11 patients with benign nonacoustic schwannomas diagnosed radiographically (n=3) or pathologically (n=8) were treated with fractionated RT with curative intent at the University of Florida. We reviewed patients' medical records to assess outcomes and toxicities from treatment. RESULTS: The median follow-up for all patients was 8.2 years (range, 2.2 to 22.7 y) and 8 years for all living patients (range, 2.2 to 22.7 y). Of the 11 patients included in the analysis, 8 (73%) were treated solely with RT, 1 (9%) was treated with postoperative RT after subtotal resection, and 2 (18%) were treated with postoperative RT after recurrence following initial surgical resection. The 5 year overall survival, disease-free survival, and local control rates were 100%. There were no grade 2 to 5 treatment toxicities. CONCLUSIONS: RT for benign nonacoustic schwannoma may be effective when used alone or in addition to surgery. Irradiation should be considered in patients for whom resection is likely to result in one or more neurological deficits. Fractionated RT to a total dose of 50 Gy provides excellent local control and minimal morbidity. PMID- 26270441 TI - Prognostic Value of Ki-67 Labeling Index and Postoperative Radiotherapy in WHO Grade II Meningioma. AB - OBJECTIVE: This study was performed to determine the clinical significance of the Ki-67 labeling index (LI) for local control (LC) in patients with World Health Organization (WHO) grade II meningioma. We also tried to discern the effect of postoperative radiotherapy (PORT) on LC depending upon the Ki-67 LI value. MATERIALS AND METHODS: The medical records and values of Ki-67 LIs were retrospectively reviewed for 50 patients who underwent surgical resection of intracranial WHO grade II meningiomas at Samsung Medical Center from May 2001 to December 2012. Forty-three patients (86%) were treated with immediate PORT. The median total radiation dose was 60 Gy (range, 54 to 60 Gy). RESULTS: The median follow-up was 47.4 months. The mean Ki-67 LI was 13% (range, 1% to 47%). Twelve patients (24.0%) showed local failure, and 8 patients (16.0%) experienced local failure even after PORT. The mean Ki-67 LI was 15% in patients with local failure (n=12) and 12% in patients without local failure (n=38). The 3-year actuarial LC was 80.5%. The 3-year overall survival was 89.5%. Ki-67 LI>13% and PORT were significant prognostic factors for LC (P=0.015 and 0.009, respectively). In patients with Ki-67 LI>13% (n=17), PORT (n=14) improved LC (P<0.001). However, PORT (n=29) did not affect LC (P=0.412) for patients with Ki-67 LI<=13% (n=33). CONCLUSIONS: Ki-67 LI can be a useful prognostic factor for LC in WHO grade II meningioma. In patients with Ki-67 LI>13%, PORT should be recommended to improve LC. PMID- 26270442 TI - Stereotactic Body Radiotherapy for Lung Metastases from Colorectal Cancer: Prognostic Factors for Disease Control and Survival. AB - OBJECTIVES: To evaluate disease control and survival after stereotactic body radiotherapy (SBRT) for lung metastases from colorectal cancer and to identify prognostic factors after treatment. METHODS: Patients with metastatic colorectal cancer to the lungs treated with SBRT from 2002 to 2013 were identified from a prospectively maintained database. Patients may have received prior systemic therapy, radiotherapy to nonthoracic sites and/or resection of thoracic and/or nonthoracic metastases. Endpoints were timed from end of SBRT and included overall survival (OS), progression-free survival, distant metastases-free survival, and local failure-free survival. Univariate and multivariate analysis using Cox proportional hazard modeling was used to identify prognostic factors. RESULTS: Sixty-five patients were identified. Before SBRT, 69.2% and 33.8% of patients received systemic therapy and lung-directed local therapy, respectively, for metastatic disease. At the time of SBRT, 64.6% had lung-only involvement. Median survivals were: OS of 20.3 months (95% confidence intervals [CI], 15.9 27.0 mo), progression-free survival of 5.7 months (95% CI, 3.2-7.0 mo), distant metastases-free survival of 5.8 months (95% CI, 3.2-7.6 mo), and local failure free survival of 15.4 months (95% CI, 8.5-21.1 mo). Nearly all (98%) patients developed distant progression. Extra lung and liver involvement at the time of initial metastases (hazard ratios [HR] 2.10) and extra lung involvement at SBRT (HR 2.67) were the only independent predictors of OS. Net gross target volume of >14.1 mL (HR 2.49) was the only independent predictor of local failure-free survival. CONCLUSIONS: Reasonable survival and local control can be achieved with SBRT. We identified several prognostic factors testable in future prospective trials that may help improve patient selection. PMID- 26270443 TI - Diagnosis of EML4-ALK Translocation With FISH, Immunohistochemistry, and Real time Polymerase Chain Reaction in Patients With Non-Small Cell Lung Cancer. AB - OBJECTIVE: To assess anaplastic lymphoma kinase (ALK) rearrangement detection with immunohistochemistry (IHC) and real-time polymerase chain reaction (RT-qPCR) in comparison with fluorescence in situ hybridization (FISH). METHODS: Tumor tissue samples from 230 patients with advanced non-small cell lung cancer (NSCLC) were analyzed by FISH to detect ALK rearrangements. Additional IHC tests using 5A4 clone and RT-qPCR (variants 1 to 5) were performed in 63 and 48 patients, respectively. RESULTS: Thirteen percent of FISH tests were not evaluable. From the remaining tests (n=200), 18 (9.0%) were ALK positive (ALK). ALK patients were significantly younger at the time of diagnosis (below 55 y, 14.3% vs. 5.5%, P=0.035), were light smokers (tobacco index <10, 12.6% vs. 4.1%, P=0.049), and presented adenocarcinoma with a mucinous component (30.8 vs. 8.0%, P=0.007). When comparing FISH with IHC using a cutoff of 1+ or 2+, and only 2+ staining intensity, the sensitivity, specificity, negative predictive value, and positive predictive value were as follows: 83.3%, 100.0%, 93.75%, and 100.0%; and 55.6%, 100.0%, 84.9%, and 100.0%, respectively. For RT-qPCR, these results were 55.6, 100, 90.7, and 100.0%, respectively. CONCLUSIONS: Our results suggest that RT qPCR is an inadequate initial test for detecting ALK-positive lung cancer. IHC is highly useful as an initial screening test for ALK rearrangement detection in NSCLC. These results contribute to the medical literature on the establishment of IHC as a standard diagnostic test for ALK rearrangements in NSCLC. PMID- 26270445 TI - The Trimodality Treatment Approach in Stage III/pN2 Non-Small Cell Lung Cancer: "Usually Appropriate" May Well be a Very Inappropriate Treatment Option. PMID- 26270444 TI - Primary Pulmonary Carcinoid Tumor: A Long-term Single Institution Experience. AB - OBJECTIVES: Primary carcinoid tumors of the lung are rare tumors which comprise approximately 0.5% to 5% of all lung malignancies in adults and roughly 20% to 30% of all carcinoid tumors. The purpose of this retrospective, descriptive study was to describe the incidence, characteristics, and outcomes of patients treated for primary pulmonary carcinoid tumor at a single institution. MATERIALS AND METHODS: All patients with a diagnosis of primary pulmonary carcinoid tumor treated from 1989 to 2009 were reviewed. Data collected included demographics, pathology, tobacco use, clinical presentation, tumor location, tumor spread, treatment, and survival. RESULTS: There were 59 cases of pulmonary carcinoid tumors: 47 typical (80%) and 12 atypical (20%). All but 4 patients underwent surgery, including 54 (92%) lung-sparing resections and 1 pneumonectomy. Five of 55 patients received concurrent adjuvant chemoradiation therapy; 4 patients with atypical and 1 with typical histology. Three additional patients with atypical carcinoid were treated only with adjuvant radiotherapy, palliative radiotherapy, or palliative chemotherapy, respectively. The Kaplan-Meier 5- and 10-year overall survivals were both 80% within the entire population. In the 88% of patients who achieved complete remission, disease-free survival was 98%. A review of a large series from the literature is also presented. CONCLUSIONS: Surgical resection was primary and adequate therapy for most typical carcinoid tumors with high overall survival and disease-free survival. Adjuvant chemotherapy or radiotherapy might be considered for patients with atypical carcinoid tumors who present with adverse pathologic findings. PMID- 26270447 TI - Incidence and Survival of Appendiceal Mucinous Neoplasms: A SEER Analysis. AB - OBJECTIVES: The aim of this study is to characterize the changes in the incidence, presentation, surgical treatment, and survival of patients with appendiceal mucinous neoplasm (AMN) over the past 4 decades using nationwide cancer surveillance data. METHODS: Patients with the diagnosis of AMN were identified in the Surveillance Epidemiology and End Results (SEER) database. Information on demographics, disease characteristics, and surgical treatment was collected. Temporal changes in AMN incidence, characteristics of cases, and survival were analyzed from 1973 to 2011. Determinants of overall survival (OS) were examined using both crude and multivariable Cox proportional hazard models. RESULTS: The overall incidence rate of AMN increased on average 3.1%/1,000,000 persons-years (P<0.001). A significant decline in the age at diagnosis was observed (P=0.014). The proportion of patients presenting with distant disease at diagnosis also significantly increased (P=0.004). Five-year survival of patients with distant stage AMN increased at a rate of 3.5%/y between 1984 and 2006 (P<0.001). Median OS was not reached for localized and regional stage disease. Median OS for distant stage disease was 42 months. CONCLUSIONS: There has been an increase in the overall incidence of AMN with an observed increase in the proportion of younger age and distant stage at diagnosis. The OS has improved over time. PMID- 26270446 TI - Soft Tissue Solitary Fibrous Tumor: Combined Surgery and Radiation Therapy Results in Excellent Local Control. AB - PURPOSE: To report survival outcomes and local control in patients with solitary fibrous tumors (SFT) treated using surgery and radiation therapy (RT). METHODS: We reviewed the medical records of 31 consecutive patients definitively treated for SFT with surgery and RT between 1982 and 2012. The median age was 51 years (range, 23 to 88 y) and tumors were evenly distributed between the head and neck (n=9, 29%), trunk (n=10, 32%), and lower extremities (n=9, 29%). The majority of tumors were large (>5 cm) (n=23, 72%). Specimens had a median of 2 mitoses/10 HPF (range, 0 to 8). Nearly half the cases were treated with postoperative RT (n=14, 45%; median dose, 58 Gy) and the other 17 patients (55%) received preoperative RT (median dose, 50 Gy). RESULTS: Median follow-up time was 59 months (range, 18 to 349 mo). The 5-year rates of local control, overall survival, and distant metastatic-free survival were 100%, 95%, and 92%, respectively. There were no local or nodal relapses and the 10-year complication rate was 6% (n=2). CONCLUSIONS: Treatment of soft tissue SFT using combined surgery and RT results in excellent local control. PMID- 26270448 TI - Effects of Adoptive Transferring Different Sources of Myeloid-Derived Suppressor Cells in Mice Corneal Transplant Survival. AB - BACKGROUND: Adoptively transferring different sources of myeloid-derived suppressor cells (MDSCs) may assist in mice corneal transplant survival. METHODS: Allogeneic full thickness corneal transplantation (donor C57BL/6 to recipient Balb/c mice) was performed. Naive myeloid cells, inflammation-induced MDSCs (iMDSCs), and tumor-induced MDSCs (tMDSCs) were purified from bone marrow of naive, cecal ligation and puncture, or tumor-bearing Balb/c mice, respectively. The inhibitory abilities of myeloid cells toward CD4(+) T cell proliferation were accessed by in vitro carboxyfluorescein diacetate, succinimidyl ester (CFSE) assays. Myeloid cells were adoptively transferred to corneal recipients by retroorbital injection after corneal transplantation. Corneal grafts were examined and photographed for a period of 45 days. The growth of corneal graft neovascularization was quantitatively measured by image editing software. Histopathology was performed to evaluate corneal graft inflammation. RESULTS: The iMDSCs and tMDSCs significantly inhibited T cell proliferation in vitro and significantly prolonged corneal allograft survival in vivo. Strikingly, iMDSC transferring significantly reduced neovascularization that was comparable to transferring of tMDSCs, without additional immunosuppression. However, additional adoptive transfer of MDSCs did not further ameliorate corneal survival in these allogeneic corneal transplantation mice. CONCLUSIONS: Inflammation-induced MDSC transfer could reduce corneal neovascularization and prolong corneal allograft survival. PMID- 26270449 TI - Risk-adapted Treatment for Severe B-Lineage Posttransplant Lymphoproliferative Disease After Solid Organ Transplantation in Children. AB - BACKGROUND: Optimal management of posttransplant lymphoproliferative disease (PTLD) remains to be defined due to heterogeneity of this condition and lack of predictors of the outcome. Here we report our experience with pediatric PTLD nonresponsive to immunosuppression (IS) withdrawal, managed after stratification into high and low risk according to the presenting features. METHODS: This is a single-center retrospective review of prospectively enrolled patients. From 2001 to 2011, 17 children were diagnosed with severe B-lineage, CD20+, PTLD after a median of 37 months (range, 5-93) from liver (12), heart (4), or multiorgan (1) transplantation. Treatment was tailored on 2 risk groups: (1) standard-risk (SR) patients received IS reduction and rituximab; (2) high-risk (HR) patients received IS discontinuation, rituximab and polychemotherapy. RESULTS: The cumulative incidence of rejection at 1 and 5 years after the diagnosis of PTLD was 35% (95% confidence interval [95% CI], 18-69%) and 53% (33-85%), respectively, whereas the disease-free survival at 1 and 5 years was 94% (95% CI, 65-99%) and 75% (45-90%), respectively. Three children died, PTLD-free, from different transplant-related complications: primary nonfunction after retransplantation (liver), cytomegalovirus disease 21 months after PTLD treatment (liver), graft dysfunction 25 months after PTLD (heart). CONCLUSIONS: Severe B lineage PTLD after solid organ transplantation may be classified as SR or HR and treated accordingly with a tailored protocol obtaining a satisfactory long-term outcome. This approach accomplishes the control of lymphoproliferation in severe forms as well as the minimization of toxicity in milder PTLDs. PMID- 26270450 TI - Efficacy of Myeloid Derived Suppressor Cells on Transplant Survival. PMID- 26270452 TI - Determining Age Effects: The Unique Contributions Provided by Longitudinal Designs. PMID- 26270451 TI - Boryl (Hetero)aryne Precursors as Versatile Arylation Reagents: Synthesis through C-H Activation and Orthogonal Reactivity. AB - (Pinacolato)boryl ortho-silyl(hetero)aryl triflates are presented as a new class of building blocks for arylation. They demonstrate unique versatility by delivering boronate or (hetero)aryne reactivity chemoselectively in a broad range of transformations. This approach enables the unprecedented postfunctionalization of fluoride-activated (hetero)aryne precursors, for example, as substrates in transition-metal catalysis, and offers valuable new possibilities for aryl boronate postfunctionalization without the use of specialized protecting groups. PMID- 26270456 TI - Impact of Aspiration Pneumonia on the Clinical Course of Progressive Supranuclear Palsy: A Retrospective Cohort Study. AB - INTRODUCTION: Although aspiration pneumonia is the most common complication of progressive supranuclear palsy (PSP), the clinical impact of aspiration pneumonia on disease course and survival has not been fully estimated. Thus, we retrospectively analyzed the prognostic factors and clinical consequences of pneumonia in PSP. METHODS: The clinical course of patients with aspiration pneumonia was surveyed. The association between baseline clinical features (2 years from disease onset) and latency to the initial development of pneumonia was investigated using survival time and Cox regression analyses. RESULTS: Ninety patients with a clinical diagnosis of PSP were observed for 5.1+/-3.8 years (mean+/-SD), and 22 had aspiration pneumonia. Subsequently, 20 patients (91%) had to discontinue oral feeding entirely and 13 (59%) died, whereas, of 68 patients without pneumonia, only three patients (4%) died. Time to initial development of pneumonia was strongly correlated with survival time (Spearman R = 0.92, P<0.001), with a mean latency of 2.3 years to death. Among baseline clinical features, early fall episodes and cognitive decline were significant predictors of pneumonia (P = 0.001 and P<0.001, respectively, log rank test). Cox regression analysis demonstrated that early fall episodes (adjusted hazard ratio: 3.9, 95% confidence interval: 1.2-12.5, P = 0.03) and cognitive decline (adjusted hazard ratio: 5.2, 95% confidence interval: 1.4-19.3, P = 0.02) independently predicted pneumonia. By contrast, dysphagia was not associated with pneumonia (P = 0.2, log rank test). CONCLUSION: Initial development of pneumonia indicates an unfavorable clinical course and predicts survival time (mean survival time 2.3 years). Patients with early falls and cognitive decline were at high risk of early development of pneumonia. PMID- 26270458 TI - Short Versus Long Intramedullary Nails in the Treatment of Pertrochanteric Hip Fractures: Incidence of Ipsilateral Fractures and Costs Associated With Each Implant. AB - OBJECTIVES: Both short intramedullary nails (SIMNs) and long intramedullary nails (LIMNs) are routinely used in the surgical treatment of pertrochanteric hip fractures. The purpose of this study was to assess the incidence of ipsilateral femur fractures after the surgical treatment of hip fractures and the overall costs associated with each implant. DESIGN: Retrospective cohort study. SETTING: Level I trauma center and 2 community hospitals. PATIENTS/PARTICIPANTS: A total of 609 patients with pertrochanteric hip fractures treated with an SIMN or LIMN from 2005 to 2011. INTERVENTION: Review of patient demographics and clinical outcomes over a 5-year follow-up period. MAIN OUTCOME MEASUREMENTS: Ipsilateral femur refracture rates were recorded for both groups, and a cost analysis was then performed to compare SIMNs and LIMNs while accounting for their observed refracture rates and surgical/hospital costs to determine the overall cost of each implant. RESULTS: Union rates were equivalent between groups and averaged over 97%. The incidence of ipsilateral femur fractures in both groups steadily increased with greater follow-up time to reach nearly 10% at 5 years. Although only 47% of all nails were locked distally, 15 of the 16 refractures occurred in nails that were not distally locked. Cost analysis revealed no significant difference in the use of short versus LIMNs over a 5-year period (P = 0.76). CONCLUSIONS: The incidence of ipsilateral femur refractures steadily rose with greater follow-up in both SIMN and LIMNs. Distally locking the initial fixation seems to protect against future femur fractures and may also affect the refracture location when using LIMNs. No differences in overall costs were seen at 1, 2, or 5 years between SIMNs and LIMNs. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID- 26270457 TI - Fate of Patients With a "Surprise" Positive Culture After Nonunion Surgery. AB - OBJECTIVE: Review the impact of unexpected positive cultures from definitive surgery for nonunion regarding postoperative treatment and ultimate result. DESIGNS: Retrospective multicenter case series. SETTING: Three level-one trauma centers. PATIENTS: Six-hundred sixty-six consecutive nonunions were treated during the study period. Four-hundred fifty-three cases (68%) were considered at risk for indolent infection (prior open fracture, surgery, or infection) and had cultures taken at the time of definitive surgery. INTERVENTION: Intraoperative cultures during definitive operative treatment of nonunions. MAIN OUTCOME MEASUREMENT: The incidence of "surprise" positive cultures was determined, and the course of the patients was documented including the use of antibiotics, surgery performed, and the outcome regarding infection and union. RESULTS: Ninety one (20%) cases had a surprise positive culture despite negative inflammatory markers. Most of bacteria isolated from the cultures were Staphylococcus species. Eight (9%) of the ninety-one cultures were considered probable contaminants and no antibiotics were given, 5 of these patients healed. The other 83 patients were treated with antibiotics, initially 66 (80%) healed and 12 (14%) remained infected. Eighty-two percent of patients with augmentation healed as compared with 86% of those not grafted. CONCLUSIONS: The treatment of nonunions is challenging, and in patients with a history of surgery or open fracture, we found that 20% had positive intraoperative cultures from the definitive surgery. We recommend intraoperative cultures for all patients undergoing revision surgery. The use of culture-specific antibiotics is justified based on the overall low rate of infection in this complex population and the high rate of chronic infection (25%) for those treated as contaminants. Patients may be counseled that a positive culture after nonunion surgery is a treatable problem but does increase the risk of infection and additional surgery as compared with those with a negative intraoperative culture. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 26270459 TI - Is Closed Reduction and Percutaneous Fixation of Unstable Posterior Ring Injuries as Accurate as Open Reduction and Internal Fixation? AB - OBJECTIVES: The objective of this retrospective review was to determine whether a closed reduction technique for unstable pelvic ring injuries is as accurate as an open technique. DESIGN: Retrospective review. SETTING: Two academic Level 1 trauma centers. PATIENTS/PARTICIPANTS: We reviewed the records of 113 patients who had unilateral unstable pelvic ring injuries (Bucholz type 3, OTA type 61-C1) treated with closed reduction and percutaneous fixation (CRPF) or open reduction with internal fixation (ORIF). INTERVENTION: Sixty patients were treated at one institution with open reduction and percutaneous iliosacral screw fixation. This involved prone positioning and a gluteus maximus sparing approach for direct visualization and reduction of the fracture. A second cohort of 53 patients was treated at a separate institution with closed reduction and percutaneous iliosacral screw fixation. This involved supine positioning and skeletal traction. MAIN OUTCOME MEASURES: Preoperative and postoperative plain radiographs of the pelvis were reviewed and standardized measurements were made to compare quality of reduction. RESULTS: We were able to measure displacement within 0.1 mm. Overall reduction quality was slightly better for the CRPF group. The largest average difference in postoperative displacement was seen at the iliac wing height on anteroposterior pelvis radiographs with 6.3 mm (range 0-19.6) in the ORIF group versus 1.9 mm (range 0-4.7) in the CRPF group. CONCLUSIONS: The closed reduction technique described here is as effective as the ORIF technique in obtaining reduction of unstable pelvic ring injuries (Bucholz type 3, OTA type 61 C1). LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID- 26270460 TI - Multiplanar Fixation for Patella Fractures Using a Low-Profile Mesh Plate. AB - Patella fractures are challenging orthopaedic injuries. Many commonly used fixation techniques can be ineffective and lead to poor clinical outcomes even with satisfactory reductions and fracture healing. In this investigation, we present the technique of cage plate fixation of patella fractures and the clinical outcomes of 9 initial patients surgically treated at our institution. This technique allows direct visualization of the articular reduction, provides multiplanar fixation, effectively stabilizes inferior pole comminution, and reduces the risk of patella vascular disruption. Using this technique, we have achieved excellent functional and radiographic outcomes. PMID- 26270461 TI - Reverse Total Shoulder Arthroplasty for Posttraumatic Sequelae. AB - OBJECTIVES: The sequelae of proximal humeral fractures can produce severe shoulder dysfunction. We assessed the results of reverse shoulder arthroplasty (RSA) for these complex problems. DESIGN: Retrospective multicenter study. SETTING: Tertiary care referral hospitals. PATIENTS: A total of 26 patients were identified who had undergone RSA for the sequelae of proximal humeral fractures. Twenty patients had follow-up beyond 2 years, averaging 44 months (range, 27-97). Patients with revision prosthetic surgery were not included in the study. The average age at surgery was 67 years (range, 31-89). INTERVENTION: All patients underwent RSA. In addition, 4 shoulders required allografts to compensate for bone loss, and 1 shoulder concomitant internal fixation of a humeral shaft nonunion. MAIN OUTCOME MEASUREMENTS: The main outcome measurement was the Neer scale. Pain relief, range of motion, and American shoulder and elbow surgeon and Simple shoulder test shoulder outcome scores were also assessed. RESULTS: Overall results in the 20 patients were considered excellent in 8 shoulders, satisfactory in 6, and unsatisfactory in 6. There was significant improvement in the visual analog pain score to 1.9 (P = 0.005), forward elevation to 137 degrees (P < 0.001), and external rotation to 39 degrees (P = 0.0002). The mean American shoulder and elbow surgeon score was 65 and the mean Simple shoulder test 6. Complications included 1 deep infection, 2 transient brachial plexopathies, and 2 cases of dislocation. CONCLUSIONS: Reconstruction of the deformed proximal humerus from fracture sequelae with RSA is complex and often requires advanced surgical techniques. Complications are not infrequent and may require further surgery. Nevertheless, satisfactory results can be achieved in most patients. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 26270462 TI - Rapid maxillary expansion in therapy-resistant enuretic children: An orthodontic perspective. AB - OBJECTIVE: To evaluate whether rapid maxillary expansion (RME) could reduce the frequency of nocturnal enuresis (NE) in children and whether a placebo effect could be ruled out. METHODS: Thirty-four subjects, 29 boys and five girls with mean age of 10.7 +/- 1.8 years suffering from primary NE, were recruited. All subjects were nonresponders to the first-line antienuretic treatment and therefore were classified as "therapy resistant." To rule out a placebo effect of the RME appliance, all children were first treated with a passive appliance for 4 weeks. Rhinomanometry (RM), acoustic rhinometry (AR), polysomnographic registration, and study casts were made at different time points. RESULTS: One child experienced severe discomfort from the RME appliance and immediately withdrew from the study. Following RME, the long-term cure rate after 1 year was 60%. The RM and AR measurements at baseline and directly after RME showed a significant increase in nasal volume and nasal airflow, and there was a statistically significant correlation between reduction in enuresis and increase in nasal volume. Six months postretention, a 100% relapse of the dental overexpansion could be noted. CONCLUSIONS: RME has a curative effect in some children with NE, which could be connected to the positive influence of RME on the sleep architecture. Normal transverse occlusion does not seem to be a contraindication for moderate maxillary expansion in attempts to cure NE in children. PMID- 26270463 TI - Rapid and Sensitive Salmonella Typhi Detection in Blood and Fecal Samples Using Reverse Transcription Loop-Mediated Isothermal Amplification. AB - Typhoid fever caused by Salmonella enterica serovar Typhi remains a significant public health problem in developing countries. Although the main method for diagnosing typhoid fever is blood culture, the test is time consuming and not always able to detect infections. Thus, it is very difficult to distinguish typhoid from other infections in patients with nonspecific symptoms. A simple and sensitive laboratory detection method remains necessary. The purpose of this study is to establish and evaluate a rapid and sensitive reverse transcription based loop-mediated isothermal amplification (RT-LAMP) method to detect Salmonella Typhi infection. In this study, a new specific gene marker, STY1607, was selected to develop a STY1607-RT-LAMP assay; this is the first report of specific RT-LAMP detection assay for typhoid. Human-simulated and clinical blood/stool samples were used to evaluate the performance of STY1607-RT-LAMP for RNA detection; this method was compared with STY1607-LAMP, reverse transcription real-time polymerase chain reaction (rRT-PCR), and bacterial culture methods for Salmonella Typhi detection. Using mRNA as the template, STY1607-RT-LAMP exhibited 50-fold greater sensitivity than STY1607-LAMP for DNA detection. The STY1607-RT LAMP detection limit is 3 colony-forming units (CFU)/mL for both the pure Salmonella Typhi samples and Salmonella Typhi-simulated blood samples and was 30 CFU/g for the simulated stool samples, all of which were 10-fold more sensitive than the rRT-PCR method. RT-LAMP exhibited improved Salmonella Typhi detection sensitivity compared to culture methods and to rRT-PCR of clinical blood and stool specimens from suspected typhoid fever patients. Because it can be performed without sophisticated equipment or skilled personnel, RT-LAMP is a valuable tool for clinical laboratories in developing countries. This method can be applied in the clinical diagnosis and care of typhoid fever patients as well as for a quick public health response. PMID- 26270465 TI - Correction: A Preliminary Randomized Double Blind Placebo-Controlled Trial of Intravenous Immunoglobulin for Japanese Encephalitis in Nepal. PMID- 26270464 TI - Failure to Use and Sustain Male Condom Usage: Lessons Learned from a Prospective Study among Men Attending STI Clinic in Pune, India. AB - BACKGROUND: Sustained or consistent use of condoms by men remains a challenge. A study was carried out to identify factors associated with failure to use condoms consistently by men attending STD clinics in Pune, India. METHOD: Among 14137 STI clinic attendees, 8360 HIV sero-negative men were enrolled in a cohort study. The changes in condom usage behavior were studied among 1284 men who returned for first scheduled quarterly follow up, 309 reported consistent condom use at the time of enrollment in the cohort. Data pertaining to heterosexual men practicing high risk behavior were analyzed to identify factors associated with change in condom use behavior using logistic regression model. Demographic, behavioral and biological factors observed to be associated with condom use were fitted in five Cox proportional hazards models to calculate hazard ratios and their 95% confidence intervals to identify independent predictors of failure to sustain condom use behavior. RESULTS: The univariate analysis showed that men who were 30 years or older in age (p = 0.002) and those who did not have contact female sex worker (FSW) were more likely to fail to sustain consistent condom use. However both these factors did not show significant association in multivariable analysis. Marital status and contact with Hijra (eunuch) in lifetime were associated with failure to change in their condom use behavior [AOR 0.33 (CI 0.13 0.82; p = 0.017)]. During the follow up of 2 years, 61 events (15.5 per 100 person years, 95% CI 12.3-19.5 years) of 'failure of condom use' were recorded despite counseling. Older age, contact with non CSW partner and presence of genital ulcer disease / discharge syndrome were significant predictors of failure to sustain condom use. DISCUSSION: Married monogamous older men, who report contact with sex worker and present with genital ulcer disease are at risk of failure to use condom after first exposure to voluntary HIV counseling and testing. This is a scenario of primary prevention program. Condom promotion and counseling needs to be reinforced through follow up counseling among this population. PMID- 26270466 TI - Letter Regarding "Adult-Onset Ligneous Conjunctivitis with Detection of a Novel Plasminogen Gene Mutation and Anti-Plasminogen IgA Antibody: A Clinicopathologic Study and Review of Literature" by Y. Tu et al. PMID- 26270468 TI - The future of lasers in onychomycosis. AB - INTRODUCTION: Laser therapy is one of the most promising device-based therapies for onychomycosis. To date, reported clinical efficacies, as well as anecdotal clinical results, have varied greatly, and the specific mechanism of action has not been well-elucidated. METHODS: Here, we provide an overview of the mechanisms of action and detailed analysis of the technical parameters involved in creating a laser that will be successfully fungicidal in onychomycosis. RESULTS: This review provides important insight into why the efficacies of laser studies reported to date vary so greatly and what is critical in order to obtain high efficacy in the clinical treatment of onychomycosis. CONCLUSIONS: There is substantial opportunity to improve the targeting and anti-targeting properties of lasers to address the specific considerations required to treat onychomycosis and, more generally, other dermal pathogens. PMID- 26270467 TI - Bacterial Landscape of Bloodstream Infections in Neutropenic Patients via High Throughput Sequencing. AB - BACKGROUND: Bloodstream infection (BSI) is a common and potentially life threatening complication in patients with hematological malignancies and therapy induced neutropenia. Administration of broad spectrum antibiotics has substantially decreased the mortality rate in febrile neutropenia, but bacterial infection is documented in only one-third or fewer of the cases. BSI is typically diagnosed by blood culture; however, this method can detect only culturable pathogens. METHODS: In the present study, a total of 130 blood samples from hematological patients receiving dose-intensive antitumoural treatment were subjected to 16S rRNA PCR and 62 of them were cultured. PCR positive samples were processed to high throughput sequencing by amplifying the V1-V3 regions of the 16S rRNA gene to obtain a full spectrum of bacteria present in BSI. RESULTS: Five phyla and 30 genera were identified with sequencing compared to 2 phyla and 4 genera with culture. The largest proportion of bacteria detected by sequencing belonged to Proteobacteria (55.2%), Firmicutes (33.4%) and Actinobacteria (8.6%), while Fusobacteria (0.4%) and Bacteroidetes (0.1%) were also detected. Ninety eight percent of the bacteria identified by sequencing were opportunistic human pathogens and 65% belonged to the normal human microbiota. CONCLUSIONS: The present study indicates that BSIs in neutropenic hosts contain a much broader diversity of bacteria, likely with host origin, than previously realized. The elevated ratio of Proteobacteria in BSI corroborates the results found in other systemic inflammatory diseases, such as inflammatory bowel disease or mucosal infections. This knowledge may become of value for tailoring antimicrobial drug administration. PMID- 26270469 TI - Efficacy of sodium hypochlorite (bleach) baths to reduce Staphylococcus aureus colonization in childhood onset moderate-to-severe eczema: A randomized, placebo controlled cross-over trial. AB - BACKGROUND: Staphylococcus aureus (S. aureus) colonization/infection is an important factor in the pathophysiology of atopic dermatitis (AD). Clinical trials have demonstrated conflicting efficacy of diluted bleach baths in treating moderate-to-severe AD. We conducted a double-blinded, placebo-controlled (water), cross-over trial among patients with AD to investigate the efficacy of bleach baths in reducing S. aureus colonization and AD severity. METHOD: In this cross over trial, 40 patients with moderate-to-severe AD were randomized to receive twice-weekly bleach and water baths, each for four consecutive weeks with a four week wash-out period in between. Condition of S. aureus growth and SCORing Atopic Dermatitis index (SCORAD) were recorded at baseline and four-weekly intervals. Patients' blood was collected in first and second visits to investigate blood eosinophil count, serum levels of total IgE and specific IgEs against Staphylococcal enterotoxins A and B. In every visit, Children Dermatology Life Quality Index (CDLQI), skin hydration (SH), transepidermal water loss (TEWL) and usage frequency of prohibited medications (topical antibiotic, steroid and oral antihistamine) were recorded. RESULTS: All 40 patients completed the trial, but 14 were non-adherent. By intention-to-treat (ITT) approach, comparing with water baths, bleach baths conferred no significant efficacy in CDLQI, SH, TEWL, blood eosinophil count, total IgE and the two specific IgEs over four weeks. Water baths caused a greater reduction in affected area of SCORAD than bleach baths ( 5.7 +/- 15.4 for water vs. 0.6 +/- 12.4 for bleach; p = 0.03) by ITT, and in objective SCORAD and affected area (p < 0.05) from per-protocol approach. Bleach baths reduced topical corticosteroid use (mean difference = 1.1 +/- 2.6 days/week; p = 0.014) and topical antibiotic use (mean difference = 1.0 +/- 2.8 days/week; p = 0.044) in within-group analysis. CONCLUSIONS: This study demonstrated that a four-week, twice-weekly regime of diluted bleach baths is not more useful than water baths in reducing S. aureus colonization/infection and improving AD. A longer treatment period is needed to evaluate if the short treatment duration was the main cause for the discrepancy in outcome from other bleach-bath trials. The usage of a portable bath tub obviates the problems associated with unavailability of bathing facilities in some families. PMID- 26270471 TI - Assessing the Extent of Adherence to the Recommended Antenatal Care Content in Malaysia: Room for Improvement. AB - BACKGROUND: Recent papers on monitoring of health services affirmed that while antenatal care (ANC) is an effective measure, quality is still a problem. Quality in maternal services "...involves providing a minimum level of care to all pregnant women..." Yet adherence to a minimum level of recommended ANC content appears to be unmet. Comprehensive review of ANC content rendered in environments with rapid changes in demographic, socio-economic, lifestyle and morbidity was sparse. Malaysia is such a country that has undergone these transitions with tremendous progress in health. However, recent progress in pregnancy outcomes is stagnating. This study aims to analyse adherence to recommended ANC; specifically, to examine the extent of adherence to recommended ANC content and to determine the factors influencing ANC content score. METHODS: A retrospective cohort study of 522 randomly selected women who used ANC was conducted. Data were extracted from individual records. The study examined adherence to essential ANC guidelines using weighted scoring for physical examination, health screening, case management, and health education. GLM Univariate analysis procedure was used to determine the factors associated with ANC content score. Binary logistic regression was used to assess ANC content level and pregnancy outcomes, controlled for ANC utilisation. RESULTS: Around half of the women had <80% of recommended ANC content documented. Health education had the lowest mean score, at around 35%. The low-risk pregnancies had a higher ANC content score than the high-risk pregnancies (78% vs. 75%; P = 0.002). The smallest clinics had a higher ANC content score than the bigger clinics (78% vs. 74-76%; P<0.001). ANC content score among the women with "adequate" ANC utilisation, as defined by the modified Adequacy of Prenatal Care Utilisation Index, was lower than the women with "adequate-plus" ANC utilisation (75% vs. 78%, P<0.001). Assessment of symphysis fundal height, foetal presentation and foetal heart auscultation were initiated earlier than recommended. Inadequate ANC content was associated with higher prevalence of preterm birth. CONCLUSIONS: Our findings indicate the presence of issues related to delivery of recommended ANC content. We advocate for all pregnant women to be ensured of adherence to the recommended ANC content. We also recommend monitoring the delivery of health advice. Conforming to recommended timing of initiation for ANC practices is essential due to resource implication and possible implication on maternal wellbeing. The association of inadequate ANC content and preterm birth may be due to lesser opportunities to receive some of the care because of lower number of ANC visits among preterm birth; this may also indicate the importance of having adequate ANC content. PMID- 26270470 TI - What Do We Really Know about Cognitive Inhibition? Task Demands and Inhibitory Effects across a Range of Memory and Behavioural Tasks. AB - Our study explores inhibitory control across a range of widely recognised memory and behavioural tasks. Eighty-seven never-depressed participants completed a series of tasks designed to measure inhibitory control in memory and behaviour. Specifically, a variant of the selective retrieval-practice and the Think/No Think tasks were employed as measures of memory inhibition. The Stroop-Colour Naming and the Go/No-Go tasks were used as measures of behavioural inhibition. Participants completed all 4 tasks. Task presentation order was counterbalanced across 3 separate testing sessions for each participant. Standard inhibitory forgetting effects emerged on both memory tasks but the extent of forgetting across these tasks was not correlated. Furthermore, there was no relationship between memory inhibition tasks and either of the main behavioural inhibition measures. At a time when cognitive inhibition continues to gain acceptance as an explanatory mechanism, our study raises fundamental questions about what we actually know about inhibition and how it is affected by the processing demands of particular inhibitory tasks. PMID- 26270473 TI - Mass Gathering Medical Care: Resource Document for the National Association of EMS Physicians Position Statement. AB - Mass gatherings are heterogeneous in terms of size, duration, type of event, crowd behavior, demographics of the participants and spectators, use of recreational substances, weather, and environment. The goals of health and medical services should be the provision of care for participants and spectators consistent with local standards of care, protection of continuing medical service to the populations surrounding the event venue, and preparation for surge to respond to extraordinary events. Pre-event planning among jurisdictional public health and EMS, acute care hospitals, and event EMS is essential, but should also include, at a minimum, event security services, public relations, facility maintenance, communications technicians, and the event planners and organizers. Previous documented experience with similar events has been shown to most accurately predict future needs. Future work in and guidance for mass gathering medical care should include the consistent use and further development of universally accepted consistent metrics, such as Patient Presentation Rate and Transfer to Hospital Rate. Only by standardizing data collection can evaluations be performed that link interventions with outcomes to enhance evidence-based EMS services at mass gatherings. Research is needed to evaluate the skills and interventions required by EMS providers to achieve desired outcomes. The event dedicated EMS Medical Director is integral to acceptable quality medical care provided at mass gatherings; hence, he/she must be included in all aspects of mass gathering medical care planning, preparations, response, and recovery. Incorporation of jurisdictional EMS and community hospital medical leadership, and emergency practitioners into these processes will ensure that on-site care, transport, and transition to acute care at appropriate receiving facilities is consistent with, and fully integrated into the community's medical care system, while fulfilling the needs of event participants. PMID- 26270472 TI - Time-course effects of aerobic exercise training on cardiovascular and renal parameters in 2K1C renovascular hypertensive rats. AB - Exercise training (Ex) has been recommended for its beneficial effects in hypertensive states. The present study evaluated the time-course effects of Ex without workload on mean arterial pressure (MAP), reflex bradycardia, cardiac and renal histology, and oxidative stress in two-kidney, one-clip (2K1C) hypertensive rats. Male Fischer rats (10 weeks old; 150-180 g) underwent surgery (2K1C or SHAM) and were subsequently divided into a sedentary (SED) group and Ex group (swimming 1 h/day, 5 days/week for 2, 4, 6, 8, or 10 weeks). Until week 4, Ex decreased MAP, increased reflex bradycardia, prevented concentric hypertrophy, reduced collagen deposition in the myocardium and kidneys, decreased the level of thiobarbituric acid-reactive substances (TBARS) in the left ventricle, and increased the catalase (CAT) activity in the left ventricle and both kidneys. From week 6 to week 10, however, MAP and reflex bradycardia in 2K1C Ex rats became similar to those in 2K1C SED rats. Ex effectively reduced heart rate and prevented collagen deposition in the heart and both kidneys up to week 10, and restored the level of TBARS in the left ventricle and clipped kidney and the CAT activity in both kidneys until week 8. Ex without workload for 10 weeks in 2K1C rats provided distinct beneficial effects. The early effects of Ex on cardiovascular function included reversing MAP and reflex bradycardia. The later effects of Ex included preventing structural alterations in the heart and kidney by decreasing oxidative stress and reducing injuries in these organs during hypertension. PMID- 26270476 TI - Detection and Characterization of Cocaine and Related Tropane Alkaloids in Coca Leaf, Cocaine, and Biological Specimens. AB - Cocaine, atropine and scopolamine are the three most important alkaloids in the tropane group. The detection of these alkaloids and their metabolites, at trace levels in biological matrices, is reviewed. These matrices include human and rat physiological fluids such as blood, urine, and saliva as well as human body tissue and hair. The detection, isolation, and determination of cocaine and related tropane alkaloids in cocaine-bearing leaf of South American and greenhouse-cultivated coca is discussed. The relationship between tropane alkaloids in coca leaf and their presence in illicit refined cocaine is addressed. A survey of modern methods for the detection of tropane alkaloids, including mass spectrometry, ultraviolet, infrared and Raman spectroscopy, gas and high-performance liquid chromatography and immunoassay techniques, is presented. PMID- 26270475 TI - Post-Operative Complications in Living Liver Donors: A Single-Center Experience in China. AB - The gap between the growing demand for available organs and the cadaveric organs facilitates the adoption of living donor liver transplantation. We retrospectively identified and evaluated the post-operative complications as per the modified Clavien classification system in 152 living liver donors at at the First Affiliated Hospital, College of Medicine, Zhejiang University between December, 2006 and June, 2014. Post-operative complications were observed in 61 patients (40.1%) in the present study, but no mortality was reported. Complications developed in 58 (40.0%) right, 1 (33.3%) left, and 2 (66.7%) lateral left hepatectomy donors. The prevalence of re-operation was 1.3%. Grade I and II complications were observed in 38 (25.0%) and 11 (7.2%) donors, respectively. Grade IIIa complications developed in 9 (5.9%) donors and only 3 (2.0%) patients reported grade IIIb complications. The most common complication was pleural effusion that occurred in 31 (20.4%) donors. No significant prognostic baseline factor was identified in this study. In conclusion, living donors experienced various complications, which were usually mild and had a good prognosis. PMID- 26270477 TI - Drugs of Abuse in Meconium. AB - The determination of fetal drug exposure is of great importance for the future development of the neonate. Meconium, the first fecal material excreted by the newborn is an excellent depository for drugs to which the fetus has been exposed. Correct diagnosis of drug use during pregnancy allows the child to receive specialized treatment and care, which will aid in learning behavioral development. Meconium analysis is gaining significant credibility as an alternative or an additional sample to neonatal or maternal urine, because meconium provides a longer history of drug use than urine and drug concentrations are higher. Therefore, number of false negative results is decreased. Meconium analysis is a relatively new scientific development. Reported analytical procedures and techniques for drugs and metabolites in meconium are predominantly cocaine-related, although other compounds have been studied. Meconium, a complex matrix, requires pre-treatment and the extraction of drugs using organic solvents and solid-phases is discussed. Preliminary drug screening using predominantly immunoassays and quantitative confirmatory analytical chromatographic methods, are reviewed. Drugs of abuse described include cocaine, amphetamines, phencyclidine, marijuana, opiates, nicotine, benzodiazepines and barbiturates. PMID- 26270474 TI - High Resolution Discovery Proteomics Reveals Candidate Disease Progression Markers of Alzheimer's Disease in Human Cerebrospinal Fluid. AB - Disease modifying treatments for Alzheimer's disease (AD) constitute a major goal in medicine. Current trends suggest that biomarkers reflective of AD neuropathology and modifiable by treatment would provide supportive evidence for disease modification. Nevertheless, a lack of quantitative tools to assess disease modifying treatment effects remains a major hurdle. Cerebrospinal fluid (CSF) biochemical markers such as total tau, p-tau and Ab42 are well established markers of AD; however, global quantitative biochemical changes in CSF in AD disease progression remain largely uncharacterized. Here we applied a high resolution open discovery platform, dMS, to profile a cross-sectional cohort of lumbar CSF from post-mortem diagnosed AD patients versus those from non-AD/non demented (control) patients. Multiple markers were identified to be statistically significant in the cohort tested. We selected two markers SME-1 (p<0.0001) and SME-2 (p = 0.0004) for evaluation in a second independent longitudinal cohort of human CSF from post-mortem diagnosed AD patients and age-matched and case-matched control patients. In cohort-2, SME-1, identified as neuronal secretory protein VGF, and SME-2, identified as neuronal pentraxin receptor-1 (NPTXR), in AD were 21% (p = 0.039) and 17% (p = 0.026) lower, at baseline, respectively, than in controls. Linear mixed model analysis in the longitudinal cohort estimate a decrease in the levels of VGF and NPTXR at the rate of 10.9% and 6.9% per year in the AD patients, whereas both markers increased in controls. Because these markers are detected by mass spectrometry without the need for antibody reagents, targeted MS based assays provide a clear translation path for evaluating selected AD disease-progression markers with high analytical precision in the clinic. PMID- 26270478 TI - Forensic Investigation of Soil and Vegetable Materials. AB - In forensic science, soil, dust, and vegetable traces have as high a value as evidence as classical traces such as fingerprints or toolmarks. It is imperative that the potential information in these traces can be identified by a combination of analytical methods selected by a qualified expert. Experience has shown that the best results can be expected when all of the aspects of evidence, including physical, chemical, mineralogical, and biological, are taken into consideration. This review provides information on successfully tried and tested methods in the forensic investigation of soil and vegetable material. PMID- 26270479 TI - Lipid Binding of the Amphipathic Helix Serving as Membrane Anchor of Pestivirus Glycoprotein Erns. AB - Pestiviruses express a peculiar protein named Erns representing envelope glycoprotein and RNase, which is important for control of the innate immune response and persistent infection. The latter functions are connected with secretion of a certain amount of Erns from the infected cell. Retention/secretion of Erns is most likely controlled by its unusual membrane anchor, a long amphipathic helix attached in plane to the membrane. Here we present results of experiments conducted with a lipid vesicle sedimentation assay able to separate lipid-bound from unbound protein dissolved in the water phase. Using this technique we show that a protein composed of tag sequences and the carboxyterminal 65 residues of Erns binds specifically to membrane vesicles with a clear preference for compositions containing negatively charged lipids. Mutations disturbing the helical folding and/or amphipathic character of the anchor as well as diverse truncations and exchange of amino acids important for intracellular retention of Erns had no or only small effects on the proteins membrane binding. This result contrasts the dramatically increased secretion rates observed for Erns proteins with equivalent mutations within cells. Accordingly, the ratio of secreted versus cell retained Erns is not determined by the lipid affinity of the membrane anchor. PMID- 26270480 TI - Selamectin Is the Avermectin with the Best Potential for Buruli Ulcer Treatment. AB - A comprehensive analysis was done to evaluate the potential use of anti-parasitic macrocyclic lactones (including avermectins and milbemycins) for Buruli ulcer (BU) therapy. A panel containing nearly all macrocyclic lactones used in human or in veterinary medicine was analyzed for activity in vitro against clinical isolates of Mycobacterium ulcerans. Milbemycin oxime and selamectin were the most active drugs against M. ulcerans with MIC values from 2 to 8 MUg/mL and 2 to 4 MUg/mL, respectively. In contrast, ivermectin and moxidectin, which are both in clinical use, showed no significant activity (MIC> 32 MUg/mL). Time-kill kinetic assays showed bactericidal activity of selamectin and in vitro pharmacodynamic studies demonstrated exposure-dependent activity. These data together with analyses of published pharmacokinetic information strongly suggest that selamectin is the most promising macrocyclic lactone for BU treatment. PMID- 26270483 TI - Correction: The Role of Conspiracist Ideation and Worldviews in Predicting Rejection of Science. PMID- 26270481 TI - Development and Characterization of Bladder Cancer Patient-Derived Xenografts for Molecularly Guided Targeted Therapy. AB - BACKGROUND: The overarching goal of this project is to establish a patient derived bladder cancer xenograft (PDX) platform, annotated with deep sequencing and patient clinical information, to accelerate the development of new treatment options for bladder cancer patients. Herein, we describe the creation, initial characterization and use of the platform for this purpose. METHODS AND FINDINGS: Twenty-two PDXs with annotated clinical information were established from uncultured unselected clinical bladder cancer specimens in immunodeficient NSG mice. The morphological fidelity was maintained in PDXs. Whole exome sequencing revealed that PDXs and parental patient cancers shared 92-97% of genetic aberrations, including multiple druggable targets. For drug repurposing, an EGFR/HER2 dual inhibitor lapatinib was effective in PDX BL0440 (progression-free survival or PFS of 25.4 days versus 18.4 days in the control, p = 0.007), but not in PDX BL0269 (12 days versus 13 days in the control, p = 0.16) although both expressed HER2. To screen for the most effective MTT, we evaluated three drugs (lapatinib, ponatinib, and BEZ235) matched with aberrations in PDX BL0269; but only a PIK3CA inhibitor BEZ235 was effective (p<0.0001). To study the mechanisms of secondary resistance, a fibroblast growth factor receptor 3 inhibitor BGJ398 prolonged PFS of PDX BL0293 from 9.5 days of the control to 18.5 days (p<0.0001), and serial biopsies revealed that the MAPK/ERK and PIK3CA-AKT pathways were activated upon resistance. Inhibition of these pathways significantly prolonged PFS from 12 day of the control to 22 days (p = 0.001). To screen for effective chemotherapeutic drugs, four of the first six PDXs were sensitive to the cisplatin/gemcitabine combination, and chemoresistance to one drug could be overcome by the other drug. CONCLUSION: The PDX models described here show good correlation with the patient at the genomic level and known patient response to treatment. This supports further evaluation of the PDXs for their ability to accurately predict a patient's response to new targeted and combination strategies for bladder cancer. PMID- 26270482 TI - A Comparison of Culture- and PCR-Based Methods to Detect Six Major Non-O157 Serogroups of Shiga Toxin-Producing Escherichia coli in Cattle Feces. AB - Culture-based methods to detect the six major non-O157 (O26, O45, O103, O111, O121 and O145) Shiga toxin-producing E. coli (STEC) are not well established. Our objectives of this study were to develop a culture-based method to detect the six non-O157 serogroups in cattle feces and compare the detection with a PCR method. Fecal samples (n = 576) were collected in a feedlot from 24 pens during a 12-week period and enriched in E. coli broth at 40 degrees C for 6 h. Enriched samples were subjected to immunomagnetic separation, spread-plated onto a selective chromogenic medium, and initially pooled colonies, and subsequently, single colonies were tested by a multiplex PCR targeting six serogroups and four virulence genes, stx1, stx2, eae, and ehxA (culture method). Fecal suspensions, before and after enrichment, were also tested by a multiplex PCR targeting six serogroups and four virulence genes (PCR method). There was no difference in the proportions of fecal samples that tested positive (74.3 vs. 77.4%) for one or more of the six serogroups by either culture or the PCR method. However, each method detected one or more of the six serogroups in samples that were negative by the other method. Both culture method and PCR indicated that O26, O45, and O103 were the dominant serogroups. Higher proportions (P < 0.05) of fecal samples were positive for O26 (44.4 vs. 22.7%) and O121 (22.9 vs. 2.3%) serogroups by PCR than by the culture method. None of the fecal samples contained more than four serogroups. Only a small proportion of the six serogroups (23/640; 3.6%) isolated carried Shiga toxin genes. The culture method and the PCR method detected all six serogroups in samples negative by the other method, highlighting the importance of subjecting fecal samples to both methods for accurate detection of the six non O157 STEC in cattle feces. PMID- 26270484 TI - Pulmonary Haemodynamics in Sickle Cell Disease Are Driven Predominantly by a High Output State Rather Than Elevated Pulmonary Vascular Resistance: A Prospective 3 Dimensional Echocardiography/Doppler Study. AB - AIMS: Patients with sickle cell disease have significant morbidity and mortality. Pulmonary hypertension is suggested to be an important contributor but its nature and severity in these patients and how best to non-invasively assess it are controversial. We hypothesised that a high-output state rather than primary pulmonary vascular pathology may be the major abnormality in sickle cell disease. This study aimed to evaluate the characteristics and severity of pulmonary hypertension in patients with sickle cell disease using detailed echocardiography. METHODS AND RESULTS: We undertook a prospective study in 122 consecutive stable outpatients with sickle cell disease and 30 age, gender and ethnicity-matched healthy controls. Echocardiographic evaluation included 3D ventricular volumes, sphericity, tissue Doppler, and non-invasive estimation of pulmonary vascular resistance. 36% of patients had a tricuspid regurgitant velocity >=2.5 m.s(-1) but only 2% had elevated pulmonary vascular resistance and the prevalence of right ventricular dysfunction was very low. Patients with raised tricuspid regurgitant velocity had significantly elevated biventricular volumes and globular left ventricular remodelling, related primarily to anaemia. In a subgroup of patients who underwent cardiac catheterization, invasive pulmonary haemodynamics confirmed the echocardiographic findings. CONCLUSIONS: Elevated cardiac output and left ventricular volume overload secondary to chronic anaemia may be the dominant factor responsible for abnormal cardiopulmonary haemodynamics in patients with sickle cell disease. 3D echocardiography with non invasive estimation of pulmonary vascular resistance represents a valuable approach for initial evaluation of cardiopulmonary haemodynamics in sickle cell disease. PMID- 26270487 TI - Screening for Anal Cancer. PMID- 26270485 TI - The Proton Pump Inhibitor Non-Responder: A Clinical Conundrum. AB - Gastroesophageal reflux disease (GERD) is a highly prevalent chronic condition where in stomach contents reflux into the esophagus causing symptoms, esophageal injury, and subsequent complications. Proton pump inhibitors (PPI) remain the mainstay of therapy for acid suppression. Despite their efficacy, significant proportions of GERD patients are either partial or non-responders to PPI therapy. Patients should be assessed for mechanisms that can lead to PPI failure and may require further evaluation to investigate for alternative causes. This monograph will outline a diagnostic approach to the PPI non-responder, review mechanisms associated with PPI failure, and discuss therapeutic options for those who fail to respond to PPI therapy. PMID- 26270486 TI - In Silico Adoption of an Orphan Nuclear Receptor NR4A1. AB - A 4.1 MUs molecular dynamics simulation of the NR4A1 (hNur77) apo-protein has been undertaken and a previously undetected druggable pocket has become apparent that is located remotely from the 'traditional' nuclear receptor ligand-binding site. A NR4A1/bis-indole ligand complex at this novel site has been found to be stable over 1 MUs of simulation and to result in an interesting conformational transmission to a remote loop that has the capacity to communicate with a NBRE within a RXR-alpha/NR4A1 heterodimer. Several features of the simulations undertaken indicate how NR4A1 can be affected by alternate-site modulators. PMID- 26270488 TI - Analysis of local chronic inflammatory cell infiltrate combined with systemic inflammation improves prognostication in stage II colon cancer independent of standard clinicopathologic criteria. AB - In Stage II colon cancer, multiple independent studies have shown that a dense intratumoural immune infiltrate (local inflammation) is associated with improved outcomes, while systemic inflammation, measured by various markers, has been associated with poorer outcomes. However, previous studies have not considered the interaction between local and systemic inflammation, nor have they assessed the type of inflammatory response compared with standard clinicopathologic criteria. In order to evaluate the potential clinical utility of inflammatory markers in Stage II colon cancer, we examined local and systemic inflammation in a consecutive series of patients with resected Stage II colon cancer between 2000 and 2010 who were identified from a prospective clinical database. Increased intratumoural chronic inflammatory cell (CIC) density, as assessed by pathologist review of hematoxylin and eosin stained slides, was used to represent local inflammation. Neutrophil-to-lymphocyte ratio (NLR) >5, as calculated from pre operative full blood counts, was used to represent systemic inflammation. In 396 eligible patients identified, there was a non-significant inverse relationship between local and systemic inflammation. Increased CIC density was significantly associated with improved overall (HR 0.45, p = 0.001) and recurrence-free survival (HR 0.37, p = 0.003). High NLR was significantly associated with poorer overall survival (HR 2.56, p < 0.001). The combination of these markers further stratified prognosis independent of standard high-risk criteria, with a dominant systemic inflammatory response (low CIC/high NLR) associated with the worst outcome (5-year overall survival 55.8%). With further validation this simple, inexpensive combined inflammatory biomarker might assist in patient selection for adjuvant chemotherapy in Stage II colon cancer. PMID- 26270489 TI - Can cognitive behaviour therapy beneficially influence arousal mechanisms in psychosis? AB - Cognitive behavioural therapy for psychosis (CBTp) is an approved adjunct therapy for patients with psychotic disorders; however, we do not fully understand the neurobiological effects that this therapy may exert. Arousal, as measured by electroencephalography (EEG), provides a useful electrophysiological marker for assessing psychotic disorders. EEG studies may therefore serve as a useful measure for assessing the underlying effects of CBTp in psychotic disorders. PMID- 26270491 TI - A Small Molecule Inhibits Deregulated NRF2 Transcriptional Activity in Cancer. AB - NRF2 serves as the master regulator of oxidative stress resistance in mammalian cells. Although NRF2 activation decreases tumorigenic events in normal cells, accumulating evidence suggests that cancers have broadly selected for NRF2 activating mutations to promote anabolic growth and chemoresistance. Small molecules which inhibit NRF2 activity may therefore offer promise as an alternative anticancer treatment in NRF2 dependent cancers. We have used a high throughput screen to identify small molecules which decrease NRF2 transcriptional activity at antioxidant response element sites. One such molecule, termed AEM1, is capable of broadly decreasing the expression of NRF2 controlled genes, sensitizing A549 cells to various chemotherapeutic agents, and inhibiting the growth of A549 cells in vitro and in vivo. Profiling of multiple cell lines for their responsiveness to AEM1 revealed that AEM1's activities are restricted to cell lines harboring mutations which render NRF2 constitutively active. PMID- 26270492 TI - Ultrafast Electrical Measurements of Isolated Silicon Nanowires and Nanocrystals. AB - We simultaneously determined the charge carrier mobility and picosecond to nanosecond carrier dynamics of isolated silicon nanowires (Si NWs) and nanocrystals (Si NCs) using time-resolved terahertz spectroscopy. We then compared these results to data measured on bulk c-Si as a function of excitation fluence. We find >1 ns carrier lifetimes in Si NWs that are dominated by surface recombination with surface recombination velocities (SRV) between ~1100-1700 cm s(-1) depending on process conditions. The Si NCs have markedly different decay dynamics. Initially, free-carriers are produced, but relax within ~1.5 ps to form bound excitons. Subsequently, the excitons decay with lifetimes >7 ns, similar to free carriers produced in bulk Si. The isolated Si NWs exhibit bulk-like mobilities that decrease with increasing excitation density, while the hot carrier mobilities in the Si NCs are lower than bulk mobilities and could only be measured within the initial 1.5 ps decay. We discuss the implications of our measurements on the utilization of Si NWs and NCs in macroscopic optoelectronic applications. PMID- 26270490 TI - The influence of Actinobacillus pleuropneumoniae infection on tulathromycin pharmacokinetics and lung tissue disposition in pigs. AB - A tulathromycin concentration and pharmacokinetic parameters in plasma and lung tissue from healthy pigs and Actinobacillus pleuropneumoniae (App)-infected pigs were compared. Tulathromycin was administered intramuscularly (i.m.) to all pigs at a single dose of 2.5 mg/kg. Blood and lung tissue samples were collected during 33 days postdrug application. Tulathromycin concentration in plasma and lung was determined by high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. The mean maximum plasma concentration (Cmax ) in healthy pigs was 586 +/- 71 ng/mL, reached by 0.5 h, while the mean value for Cmax of tulathromycin in infected pigs was 386 +/- 97 ng/mL after 0.5 h. The mean maximum tulathromycin concentration in lung of healthy group was calculated as 3412 +/- 748 ng/g, detected at 12 h, while in pigs with App, the highest concentration in lung was 3337 +/- 937 ng/g, determined at 48 h postdosing. The higher plasma and lung concentrations in pigs with no pulmonary inflammation were observed at the first time points sampling after tulathromycin administration, but slower elimination with elimination half-life t1/2el = 126 h in plasma and t1/2el = 165 h in lung, as well as longer drug persistent in infected pigs, was found. PMID- 26270493 TI - AlxC Monolayer Sheets: Two-Dimensional Networks with Planar Tetracoordinate Carbon and Potential Applications as Donor Materials in Solar Cell. AB - We perform a global search of the most stable structures of 2D stoichiometric AlxC (x = 1/3, 1, 2, and 3) monolayer sheets. In the most stable 2D planar AlC network, every carbon atom is tetracoordinated. In addition to the structure of AlC, structures of the most stable Al2C and Al3C monolayer sheets are also predicted for the first time. AlC and Al2C monolayers are semiconducting, while Al3C monolayer is metallic. In particular, Al2C monolayer possesses a bandgap of 1.05 eV (based on HSE06 calculation), a value suitable for photovoltaic applications. Moreover, three Al2C/WSe2, Al2C/MoTe2, and AlC/ZnO van der Waals heterobilayers are investigated, and their power conversion efficiencies are estimated to be in the range of 12-18%. The near-perfect match in lattice constants between the Al2C monolayer and PdO (100) surface suggests strong likelihood of experimental realization of the Al2C monolayer on the PdO (100) substrate. PMID- 26270494 TI - Exceptional Excited-State Lifetime of an Iron(II)-N-Heterocyclic Carbene Complex Explained. AB - Earth-abundant transition-metal complexes are desirable for sensitizers in dye sensitized solar cells or photocatalysts. Iron is an obvious choice, but the energy level structure of its typical polypyridyl complexes, featuring low-lying metal-centered states, has made such complexes useless as energy converters. Recently, we synthesized a novel iron-N-heterocyclic carbene complex exhibiting a remarkable 100-fold increase of the lifetime compared to previously known iron(II) complexes. Here, we rationalize the measured excited-state dynamics with DFT and TD-DFT calculations. The calculations show that the exceptionally long excited-state lifetime (~9 ps) is achieved for this Fe complex through a significant destabilization of both triplet and quintet metal-centered scavenger states compared to other Fe(II) complexes. In addition, a shallow (3)MLCT potential energy surface with a low-energy transition path from the (3)MLCT to (3)MC and facile crossing from the (3)MC state to the ground state are identified as key features for the excited-state deactivation. PMID- 26270495 TI - Au25 Clusters Containing Unoxidized Tellurolates in the Ligand Shell. AB - We report herein the synthesis and characterization of Au25 clusters containing tellurolates (TePh) in the ligand shell ([Au25(TePh)n(SC8H17)18-n](-); n = 1-18). [Au25(TePh)n(SC8H17)18-n](-) clusters were synthesized by reacting [Au25(SC8H17)18](-) with diphenyl ditelluride ((PhTe)2) in solution. Characterization of the products by mass spectrometry and X-ray absorption fine structure analysis revealed that the tellurolates in [Au25(TePh)n(SC8H17)18-n]( ), unlike those in tellurolate-protected gold nanoparticles, were not oxidized. Various experiments on the products and theoretical calculations on related clusters revealed that protection by the tellurolates distorts (expands) the central Au13 core and decreases the HOMO-LUMO gap of the Au25 clusters. PMID- 26270496 TI - Efficient Self-Propelling of Small-Scale Condensed Microdrops by Closely Packed ZnO Nanoneedles. AB - Realizing the efficient self-propelling of small-scale condensed microdrops is very challenging but extremely important to design and develop advanced condensation heat transfer nanomaterials and devices, for example, for power generation and thermal management. Here, we present the efficient self-propelling of small-scale condensed microdrops on the surface of closely packed ZnO nanoneedles, as-synthesized by facile, rapid, and inexpensive wet chemical crystal growth followed by hydrophobic modification. Compared with flat surfaces, the nanostructured surfaces with the same low-surface-energy chemistry possess far higher time-averaged density of condensed droplets at the microscale, among which those with diameters below 10 MUm occupy more than 80% of the total drop number of residual condensates. Theoretical analyses clearly reveal that this remarkable property should be ascribed to the extremely low solid-liquid adhesion of the surface nanostructure, where excess surface energy released from the coalescence of smaller condensed microdrops can be sufficient to ensure the self propelled jumping of merged microdrops. PMID- 26270497 TI - Trapping of Mobile Pt Species by PdO Nanoparticles under Oxidizing Conditions. AB - Pt is an active catalyst for diesel exhaust catalysis but is known to sinter and form large particles under oxidizing conditions. Pd is added to improve the performance of the Pt catalysts. To investigate the role of Pd, we introduced metallic Pt nanoparticles via physical vapor deposition to a sample containing PdO nanoparticles. When the catalyst was aged in air, the Pt particles disappeared, and the Pt was captured by the PdO, forming bimetallic Pt-Pd nanoparticles. The formation of metallic Pt-Pd alloys under oxidizing conditions is indeed remarkable but is consistent with bulk thermodynamics. The results show that mobile Pt species are effectively trapped by PdO, representing a novel mechanism by which Ostwald ripening is slowed down. The results have implications for the development of sinter-resistant catalysts and help explain the improved performance and durability of Pt-Pd in automotive exhaust catalytic converters. PMID- 26270498 TI - Photochemistry of Pheomelanin Building Blocks and Model Chromophores: Excited State Intra- and Intermolecular Proton Transfer. AB - Pheomelanins, the epidermal pigments of red-haired people responsible for their enhanced UV susceptibility, contain 1,4-benzothiazines and 1,3-benzothiazole as main structural components. Despite the major role played in pheomelanin phototoxicity, the photoreactivity of these species has so far remained unexplored. Static and time-resolved fluorescence spectroscopy was used to identify excited-state reactions of the two main pheomelanin benzothiazole building blocks, namely, the 6-(2-amino-2-carboxyethyl)-4-hydroxy-1,3 benzothiazole (BT) and the 2-carboxy derivative (BTCA) together with model chromophores lacking some of the ionizable functions. The results show that in aqueous buffer solution the OH at 4-position and the benzothiazole nitrogen atom control the photochemistry of both BT and BTCA via excited-state proton transfer to solvent (ESPT) and excited-state intramolecular proton transfer (ESIPT), while the amino acidic groups of the alanyl chain have a minor influence on the photochemistry. The ESPT and ESIPT produce several different excited-state ionic species with lifetimes ranging from ~100 ps to ~3 ns. PMID- 26270499 TI - g-C3N4-Based Photocatalysts for Hydrogen Generation. AB - Graphitic carbon nitride (g-C3N4)-based photocatalysts have attracted dramatically increasing interest in the area of visible-light-induced photocatalytic hydrogen generation due to the unique electronic band structure and high thermal and chemical stability of g-C3N4. This Perspective summarizes the recent significant advances on designing high-performance g-C3N4-based photocatalysts for hydrogen generation under visible-light irradiation. The rational strategies such as nanostructure design, band gap engineering, dye sensitization, and heterojunction construction are described. Finally, this Perspective highlights the ongoing challenges and opportunities for the future development of g-C3N4-based photocatalysts in the exciting research area. PMID- 26270500 TI - Atomic-Scale Surface Local Structure of TiO2 and Its Influence on the Water Photooxidation Process. AB - The water photooxidation reaction on TiO2 and related metal oxides has been attracting strong attention from the point of view of solar water splitting. The water photooxidation reaction (i.e., oxygen evolution reaction) accompanies three other kinds of side reactions (photoluminescence (PL), surface roughening, and nonradiative recombination). These reactions are competitive with each other, and the ratio of their quantum efficiencies strongly depends on the atomic-scale surface local structure. This Perspective focuses on the atomic-scale surface local structure dependence of those four kinds of competitive reactions on a TiO2 (rutile) single-crystal electrode on which not only a terrace structure but also step structures were strictly controlled. The experimental results are discussed based on the reaction model of water photooxidation that we previously proposed. The photocatalytic activity of the TiO2 surface roughened by the photoinduced roughening process is also focused on. PMID- 26270501 TI - Graphical Excellence. PMID- 26270502 TI - Near-Unity Reaction Probability in Olefin Hydrogenation Promoted by Heterogeneous Metal Catalysts. AB - The kinetics of the hydrogenation of ethylene on platinum surfaces was studied by using high-flux effusive molecular beams and reflection-absorption infrared spectroscopy (RAIRS). It was determined that steady-state ethylene conversion with probabilities close to unity could be achieved by using beams with ethylene fluxes equivalent to pressures in the mTorr range and high (>=100) H2:C2H4 ratios. The RAIRS data suggest that the high reaction probability is possible because such conditions lead to the removal of most of the ethylidyne layer known to form during catalysis. The observations from this study are contrasted with those under vacuum, where catalytic behavior is not sustainable, and with catalysis under more realistic atmospheric pressures, where reaction probabilities are estimated to be much lower (<=1 * 10(-5)). PMID- 26270503 TI - Growth of Pt-Pd Nanoparticles Studied In Situ by HRTEM in a Liquid Cell. AB - The growth of Pt-Pd nanoparticles from organometallic precursors is studied in situ in real time by HRTEM in a graphene oxide liquid cell. The reduction of the metal precursors is induced by the electron beam. During the growth, the particles rearrange their internal structure to form faceted single crystals. The growth is compatible with the Lifshitz-Slyozov-Wagner (LSW) mechanism in the limiting case of a reaction-limited process. The same particles are also synthesized ex situ by using a chemical reducing agent and observed in HRTEM. PMID- 26270504 TI - Molecular Friction-Induced Electroosmotic Phenomena in Thin Neutral Nanotubes. AB - We reveal by classical molecular dynamics simulations electroosmotic flows in thin neutral carbon (CNT) and boron nitride (BNT) nanotubes filled with ionic solutions of hydrated monovalent atomic ions. We observe that in (12,12) BNTs filled with single ions in an electric field, the net water velocity increases in the order of Na(+) < K(+) < Cl(-), showing that different ions have different power to drag water in thin nanotubes. However, the effect gradually disappears in wider nanotubes. In (12,12) BNTs containing neutral ionic solutions in electric fields, we observe net water velocities going in the direction of Na(+) for (Na(+), Cl(-)) and in the direction of Cl(-) for (K(+), Cl(-)). We hypothesize that the electroosmotic flows are caused by different strengths of friction between ions with different hydration shells and the nanotube walls. PMID- 26270506 TI - Coarse-Grain Model Simulations of Nonequilibrium Dynamics in Heterogeneous Materials. AB - A suite of computational tools is described for particle-based mesoscale simulations of the nonequilibrium dynamics of energetic solids, including mechanical deformation, phase transitions, and chemical reactivity triggered by shock or thermal loading. The method builds upon our recent advances both in generating coarse-grain models under high strains and in developing a variant of dissipative particle dynamics (DPD) that includes chemical reactions. To describe chemical reactivity, a coarse-grain particle equation-of-state was introduced into the constant-energy DPD variant that rigorously treats complex chemical reactions and the associated chemical energy release. As illustration of these developments, we present simulations of shock compression of an RDX crystal and its thermal decomposition under high temperatures. We also discuss our current efforts toward a highly scalable domain-decomposition implementation that extends applicability to micrometer-size simulations. With appropriate parametrization, the method is applicable to other materials whose dynamic response is driven by microstructural heterogeneities. PMID- 26270505 TI - Towards Understanding Photodegradation Pathways in Lignins: The Role of Intramolecular Hydrogen Bonding in Excited States. AB - The photoinduced dynamics of the lignin building blocks syringol, guaiacol, and phenol were studied using time-resolved ion yield spectroscopy and velocity map ion imaging. Following irradiation of syringol and guaiacol with a broad-band femtosecond ultraviolet laser pulse, a coherent superposition of out-of-plane OH torsion and/or OMe torsion/flapping motions is created in the first excited (1)pipi* (S1) state, resulting in a vibrational wavepacket, which is probed by virtue of a dramatic nonplanar -> planar geometry change upon photoionization from S1 to the ground state of the cation (D0). Any similar quantum beat pattern is absent in phenol. In syringol, the nonplanar geometry in S1 is pronounced enough to reduce the degree of intramolecular H bonding (between OH and OMe groups), enabling H atom elimination from the OH group. For guaiacol, H bonding is preserved after excitation, despite the nonplanar geometry in S1, and prevents O-H bond fission. This behavior affects the propensities for forming undesired phenoxyl radical sites in these three lignin chromophores and provides important insight into their relative "photostabilities" within the larger biopolymer. PMID- 26270507 TI - Extremely High Two-Photon Absorbing Graphene Oxide for Imaging of Tumor Cells in the Second Biological Window. AB - Cancer, a life-threatening disease, has become a global pandemic. Targeted tumor imaging using near-infrared (NIR) light is the key to improve the penetration depth and it is highly promising for clinical tumor diagnostics. Driven by this need, in this Letter we have reported aptamer conjugated graphene oxide-based two photon imaging of breast tumor cells selectively. Reported data indicate that there is an extremely high two-photon absorption from aptamer conjugated graphene oxide (sigma2PA = 46890 GM). Experimental data show that two-photon luminescence signal remains almost unchanged even after 2 h of illuminations. Reported results show that S6 RNA aptamers conjugated graphene oxide-based two-photon fluorescence can be used for selective two-photon imaging of SK-BR-3 breast tumor cell in second biological transparency windows using 1100 nm wavelength. Experimental data demonstrate that it is highly capable of distinguishing targeted breast cancer SK-BR-3 cells from other nontargeted MDA-MB-231 breast cancer cells. PMID- 26270508 TI - Vibrationally Resolved Photoelectron Spectroscopy of the Model GFP Chromophore Anion Revealing the Photoexcited S1 State Being Both Vertically and Adiabatically Bound against the Photodetached D0 Continuum. AB - The first excited state of the model green fluorescence protein (GFP) chromophore anion (S1) and its energy level against the electron-detached neutral radical D0 state are crucial in determining the photophysics and the photoinduced dynamics of GFP. Extensive experimental and theoretical studies, particularly several very recent gas-phase investigations, concluded that S1 is a bound state in the Franck Condon vertical region with respect to D0. However, what remains unknown and challenging is if S1 is bound adiabatically, primarily due to lack of accurate experimental measurements as well as due to the close proximity in energy for these two states that even sophisticated high-level ab initio calculations cannot reliably predict. Here, we report a negative ion photoelectron spectroscopy study on the model GFP chromophore anion, the deprotonated p-hydroxybenzylidene-2,3 dimethylimidazolinone anion (HBDI(-)) taken under low-temperature conditions with improved energy resolution. Despite the considerable size and low symmetry of the molecule, resolved vibrational structures were obtained with the 0-0 transition being the most intense peak. The adiabatic (ADE) and vertical detachment (VDE) energies therefore are determined both to be 2.73 +/- 0.01 eV, indicating that the detached D0 state is 0.16 eV higher in energy than the photon excited S1 state. The accurate ADE and VDE values and the well-resolved photoelectron spectra reported here provide much needed robust benchmarks for future theoretical investigations. PMID- 26270509 TI - Hole-Conductor-Free Mesoscopic TiO2/CH3NH3PbI3 Heterojunction Solar Cells Based on Anatase Nanosheets and Carbon Counter Electrodes. AB - A hole-conductor-free fully printable mesoscopic TiO2/CH3NH3PbI3 heterojunction solar cell was developed with TiO2 nanosheets containing high levels of exposed (001) facets. The solar cell embodiment employed a double layer of mesoporous TiO2 and ZrO2 as a scaffold infiltrated by perovskite as a light harvester. No hole conductor or Au reflector was employed. Instead, the back contact was simply a printable carbon layer. The perovskite was infiltrated from solution through the porous carbon layer. The high reactivity of (001) facets in TiO2 nanosheets improved the interfacial properties between the perovskite and the electron collector. As a result, photoelectric conversion efficiency of up to 10.64% was obtained with the hole-conductor-free fully printable mesoscopic TiO2/CH3NH3PbI3 heterojunction solar cell. The advantages of fully printable technology and the use of low-cost carbon-materials-based counter electrode and hole-conductor-free structure provide this design a promising prospect to approach low-cost photovoltaic devices. PMID- 26270510 TI - Chromophore Bending Controls Fluorescence Lifetime in Single Conjugated Polymer Chains. AB - Single-molecule spectroscopy of conjugated polymers offers unique insight into the interplay between the spatial arrangement of monomer units-twisting and bending-and the characteristics of the primary excitonic photoexcitation, provided that a single conjugated segment can be isolated. beta-phase polyfluorene constitutes an ideal model to study variations in intermonomeric coupling, determined by nanoscale molecular shape, on the fundamental optical transition. If structural relaxation in the excited state is weak, exciton self trapping occurs stochastically along the conjugated segment. Bending of the pi system is then revealed by a reduction in single-photon polarization anisotropy, correlating directly with increased fluorescence lifetime. Strong relaxation raises emission anisotropy because of deterministic exciton localization, decelerating fluorescence decay due to a decrease in exciton coherence length. PMID- 26270511 TI - Acquired factor V inhibitor after exposure to topical human thrombin related to an otorhinolaryngological procedure. AB - Acquired factor V (FV) inhibitors occur rarely and classically develop after exposure to bovine thrombin. The clinical presentation is variable, ranging from asymptomatic with incidental laboratory abnormalities to significant bleeding. With the development of human-derived thrombin agents, bovine thrombin is less frequently used. We report a case of an acquired FV inhibitor that developed in a patient after exposure to human thrombin used as a hemostatic agent during an otorhinolaryngology surgical procedure. Our review of the literature revealed only one prior reported case of FV inhibitor after exposure to human thrombin. Hematologists and surgeons should be aware of this rare, but potentially life threatening, complication in the postprocedural setting. PMID- 26270513 TI - [Ubiquitin as a regulator of IFN production in the antiviral response]. AB - Type I interferons (IFNs) are important in the immune response. After pathogen detection, host cells rapidly trigger innate immune mechanisms such as inflammatory cytokines production, thus leading to the eradication of the invading virus. Such mechanisms engage signaling cascades which, in the initial phase of infection, lead to the activation of the NF-kappaB pathway and IFN regulatory factors (IRF-3, IRF-7) which directly control the production of IFNs. Proper regulation of IFN induction takes place by ubiqutination and allows to maintain a balance between the activation and inhibition of the immune system response due to an infection. Studies in recent years indicate that ubiquitination of proteins can affect both proteasomal degradation as well as the non-canonical pathway which results in the regulation of their activity. The type of ubiquitination primarily depends on the attachment of ubiquitin chain to thetarget protein but also on the activity of proteases from DUBs family. The ubiquitin pathway holds many potential therapeutic targets. Thus, the more detailed understanding of the mechanism of ubiquitination and the role of ubiquitin involved in IFNs production pathways may provide a turning point for both antiviral therapy and autoimmune diseases. PMID- 26270512 TI - Ruthenium(II) and osmium(II) vinyl complexes as highly sensitive and selective chromogenic and fluorogenic probes for the sensing of carbon monoxide in air. AB - The detection of carbon monoxide in solution and air has been achieved using simple, inexpensive systems based on the vinyl complexes [M(CH?CHR)Cl(CO)(BTD)(PPh3 )2 ] (R=aryl, BTD=2,1,3-benzothiadiazole). Depending on the nature of the vinyl group, chromogenic and fluorogenic responses signalled the presence of this odourless, tasteless, invisible, and toxic gas. Solutions of the complexes in CHCl3 underwent rapid change between easily differentiated colours when exposed to air samples containing CO. More significantly, the adsorption of the complexes on silica produced colorimetric probes for the naked eye detection of CO in the gas phase. Structural data for key species before and after the addition of CO were obtained by means of single X-ray diffraction studies. In all cases, the ruthenium and osmium vinyl complexes studied showed a highly selective response to CO with exceptionally low detection limits. Naked eye detection of CO at concentrations as low as 5 ppb in air was achieved with the onset of toxic levels (i.e., 100 ppm), thus resulting in a remarkably clear colour change. Moreover, complexes bearing pyrenyl, naphthyl, and phenanthrenyl moieties were fluorescent, and greater sensitivities were achieved (through turn on emission fluorescence) in the presence of CO both in solution and air. This behaviour was explored computationally using time-dependent density functional theory (TDDFT) experiments. In addition, the systems were shown to be selective for CO over all other gases tested, including water vapour and common organic solvents. Supporting the metal complexes on cellulose strips for use in an existing optoelectronic device allows numerical readings for the CO concentration to be obtained and provision of an alarm system. PMID- 26270514 TI - [Stem cells and growth factors in wound healing]. AB - Wound healing is a complex process which depends on the presence of various types of cells, growth factors, cytokines and the elements of extracellular matrix. A wound is a portal of entry for numerous pathogens, therefore during the evolution wound healing process has formed very early, being critical for the survival of every individual. Stem cells, which give rise to their early descendants progenitor cells and subsequently differentiated cells, play a specific role in the process of wound healing. Among the most important cells which take part in wound healing the following cells need to be distinguished: epidermal stem cells, dermal precursor of fibroblasts, adipose-derived stem cells as well as bone marrow cells. The activity of these cells is strictly regulated by various growth factors, inter alia epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor (TGF), vascular endothelial growth factor (VEGF). Any disorders in functioning of stem cells and biological activity of growth factors may lead to the defects in wound healing, for instance delayed wound healing or creation of hypertrophic scars. Therefore, knowledge concerning the mechanisms of wound healing is extremely essential from clinical point of view. In this review the current state of the knowledge of the role of stem cells and growth factors in the process of wound healing has been presented. Moreover, some clinical aspects of wound healing as well as the possibility of the therapy based on stem cells and growth factors have included. PMID- 26270515 TI - [The interleukin-10 in the central nervous system]. AB - Cytokines, including interleukin-10 (IL-10), are cell signaling molecules taking part in cell-to-cell communication, cell proliferation, differentiation, migration and apoptosis. Cytokines also have the ability to induce, regulate, and inhibit inflammation. Cytokines are produced mainly by activated peripheral immune cells, but due to dissemination of the concept of the central nervous system as an immunologically specialized zone, it is considered that cytokine signaling is one of the components of the immune system which can modulate brain functioning. IL-10 shows immunosuppressive properties, and since expression of this cytokine has been shown in the central nervous system, researchers have started to investigate the therapeutic possibilities of IL-10 action in the context of neurodegenerative diseases, which may involve neuroinflammation in their pathogenesis. Recent studies using cell cultures or animal models of neurodegenerative disorders have shown that the importance of IL-10 in the central nervous system goes beyond the anti-inflammatory activity of this cytokine. Involvement of IL-10 in neuroprotection, neurogenesis, regulation of the stress response and hippocampal synaptic plasticity connected with learning and memory is suggested. PMID- 26270516 TI - [The importance of gamma-linolenic acid in the prevention and treatment]. AB - The etiology of diet-related disorders is closely associated with dietary factors. A special role is attributed to intake of fat and fatty acid profile, both quantitative and qualitative. For prevention and treatment of the abovementioned diseases a proper supply of unsaturated fatty acids plays a significant role, because of their particular importance to health. gamma Linolenic acid (GLA), with three double bonds in the carbon chain, also known as all-cis 6,9,12-octadecatrienoic acid, belongs to the n-6 family of fatty acids. It plays biologically important functions in the human body, such as being a substrate for eicosanoids synthesis, involvement in the transport and oxidation of cholesterol, and being one of the components of lipid membrane. Its inadequate dietary intake or impaired formation is the cause of many inflammatory and degenerative diseases. A rich source of this fatty acid is vegetable oils, until recently used mainly in folk medicine. Nowadays, studies conducted both in animal models and in humans suggest its health-promoting properties in the prevention and treatment of atopic dermatitis, cardiovascular diseases, diabetes, cancers and rheumatoid arthritis. PMID- 26270517 TI - [Selected endothelial hemostatic markers in patients with peripheral arterial disease after endovascular revascularization and restenosis formation]. AB - Surgical and endovascular revascularization of ischemic legs in patients with peripheral arterial disease (PAD) can damage the arterial wall (endothelial and smooth muscle cells). Hemostatic factors released during endothelial dysfunction can lead to restenosis. 1. Determination of selected endothelial hemostatic factors in PAD patients and a reference group. 2. Prospective observation of new restenosis appearance in PAD patients after endovascular revascularization. 3. Comparison of selected endothelial hemostatic factors between non-restenotic and restenotic PAD patients. 150 PAD patients after endovascular revascularization - 90 men and 60 women, aged 44-88 (mean 65.5) years - were examined. During one year observation after the revascularization procedures in 38 PAD patients restenosis occurred, when blood samples were also collected. The reference group consisted of 53 healthy persons - 44 men and 9 women, aged 20-56 years. Blood was drawn in the morning into 3.2% sodium citrate at a ratio of 9:1. Tissue factor (TF), tissue factor pathway inhibitor (TFPI), thrombomodulin (TM), von Willebrand factor (vWF) and tissue plasminogen activator (t-PA) were measured in plasma with commercial tests using the enzyme immunoassay. In the plasma of PAD patients after revascularization, the concentrations of TF and vWF were significantly higher, TM lower, TFPI and t-PA similar compared to the reference group. Six months after revascularization the level of TF had increased and vWF had significantly decreased. The endothelial hemostatic factors before and after restenosis did not significantly differ except TF, which after restenosis was higher. Increased TF and vWF levels in PAD patients indicate arterial endothelial cell damage, by atherosclerotic and revascularization processes. In PAD patients with restenosis compared to these patients before restenosis the determined endothelial hemostatic factors, except TF level, did not significantly differ. Perhaps TF participates in restenosis formation. PMID- 26270518 TI - [Vascular access in diabetic patients. Are these patients "difficult"?]. AB - Diabetics with stage V chronic kidney disease (CKD) on hemodialysis (HD) are considered as "difficult patients", because of problems with creation of the vascular access. There is controversy regarding the results and recommendations for preparation of the vascular access in these patients. The aim of this retrospective study was to evaluate the results of creating different types of arteriovenous fistula (AVFs) in consecutive series of patients starting dialysis treatment. The analysis was performed in 741 patients (385 females and 356 males), average age 61.4+/-7 years, who started dialysis treatment in our department between January 2005 and December 2012. Native AVFs were created in all patients. No patients received an AVF requiring synthetic graft material. The number of patients with diabetic nephropathy was 166 (22.4%). Among them, 30 (18%) had type 1 diabetes and 136 (82%) type 2. In this group the occurrence of calcification in the forearm artery was estimated on the basis of physical examination, Allan's test, Doppler ultrasound and forearm X-ray. In a subgroup of patients with atherosclerotic changes in the arterial system the frequency of failed AVFs was analyzed. These results were compared with the group without diabetes. The number of procedures necessary for successfu AVF creation and type of access was counted in both groups. The assessment of the procedure frequency and AVF location in diabetic and in non-diabetic patients was made by chi2 test with Yates correction. In the group of 166 patients with diabetes, in 100 cases (60%) atherosclerotic changes in forearm arteries were observed. In a subgroup of 30 patients with type 1 diabetes atherosclerosis was observed in 17 adults (57%). In this subgroup creation of a suitable forearm AVF in the first procedure in 9 patients was possible and in the other 8 cases the atherosclerotic changes necessitated repeated procedures and were an important obstacle to create the AVF. In the subgroup of 136 patients with type 2 diabetes, atherosclerosis in the forearm artery was observed in 83 cases (61%). In this subgroup the creation of a native AVF was possible in 40 patients during the first procedure and in 43 cases additional intervention was needed, but only in 8 cases was atherosclerosis the cause of fistula failure. Generally, among 166 patients only in 16 cases (10%) did atherosclerosis present an important obstacle for AVF creation, but the number of necessary procedures to create one functioning AVF was significantly greater in this population (2 v 2.7, p=0.0001). A functioning AVF in patients with diabetes was found significantly frequently in the arm localization in comparison to non-diabetic patients (4.3 v 2%, p=0.0478). Atherosclerotic changes in forearm arteries in diabetic patients appear in 60% of hemodialysis patients and make it difficult to create an AVF only in 10% of diabetic patients, but it is possible to create a native AVF in 90% of diabetic patients, although this requires more procedures. In patients with diabetes, AVF in the wrist region should be preferred. PMID- 26270519 TI - Comparison of antiemetic efficacy and safety of palonosetron vs ondansetron in the prevention of chemotherapy-induced nausea and vomiting in children. AB - BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) in children is a major side effect despite the use of combination antiemetic drugs. OBJECTIVE: To compare the efficacy and safety profile of palonosetron, a second-generation 5 hydroxytryptamine-3 (5-HT3) receptor antagonist, with ondansetron in the prevention of CINV in children. METHODS: A prospective, randomized, crossover study was conducted in patients aged 2-18 years. 160 chemotherapy cycles, consisting of chemotherapy drugs with moderate- and high-emetogenic potential, were studied. The study group received a single dose of intravenous (IV) palonosetron 5 mcg/kg, and the standard group received IV ondansetron 5 mg/m2 every 8 hours while receiving chemotherapy. The patients were observed for vomiting, use of rescue antiemetic medications, and nausea from Day 1 0-72 hours after completion of each chemotherapy cycle. All adverse events during the study period were recorded. RESULTS: The overall percentage of patients with complete response (CR) in the palonosetron and ondansetron groups were 60% and 56.2%, respectively (?? = .631). The CR rates in the palonosetron and ondansetron groups were 75% and 70%, respectively, in the acute phase (?? = .479), and 68.8% and 65%, respectively, in the delayed phase (?? = .614). There was no statistically significant difference in the CR rates cross both groups. CONCLUSION: A single dose of palonosetron is noninferior to ondansetron in the prevention of CINV in children and can be considered as an alternative antiemetic drug. There was no significant difference in adverse effects between the palonosetron and ondansetron group. PMID- 26270520 TI - Simultaneous integrated boost using stereotactic radiosurgery for resected brain metastases: rationale, dosimetric parameters, and preliminary clinical outcomes. AB - BACKGROUND: Radiosurgery has been shown to reduce the rates of local recurrence in the postoperative bed after the resection of brain metastases, but the ideal radiation dose has not been well defined. OBJECTIVE: To present dosimetric parameters and preliminary clinical outcomes for patients undergoing postoperative stereotactic radiosurgery (SRS) with simultaneous integrated boost (SIB) for brain metastases. METHODS AND MATERIALS: 3 patients underwent surgery for a dominant metastatic focus and had residual or recurrent disease in the resection cavity. Our technique delivered a low dose to the resection cavity with an SIB dose to the gross tumor. Clinical target volume (CTV) was the magnetic resonance (MR)-defined resection cavity. Gross tumor volume (GTV) was the MR defined residual disease. No additional margin was added to either the resection cavity or the residual disease area. Doses ranged from 14-15 Gy for CTV and 17-18 Gy for GTV prescribed to the 71%-78% isodose line. A traditional postoperative radiosurgery plan was constructed for each patient, and dosimetric values were compared using the paired t-test. RESULTS: 3 patients were treated at our institution using SRS with SIB. No patient experienced local recurrence. 2 patients developed distant brain failure (mean, 3.5 months). No grade 3 or greater toxicities were observed. The volume of brain receiving 12 Gy was significantly reduced using SIB compared with traditional postoperative SRS (?? = .04). There were no differences in the maximum dose delivered to the tumor (?? = .15) and cavity (?? = .13). The average mean cavity dose was 16.20 Gy using the SIB plan, compared with 19.71 Gy using the traditional plan (?? = .05). CONCLUSIONS: In patients with either recurrent or residual disease following surgical resection, SRS using SIB is technically feasible and safe. PMID- 26270521 TI - Impact of nurse navigation on timeliness of diagnostic medical services in patients with newly diagnosed lung cancer. AB - BACKGROUND: The Summa Cancer Institute in Akron, Ohio, sought to improve access to and the timeliness of lung cancer care by hiring an oncology-certified nurse navigator. The nurse navigator was charged with coordinating diagnostic procedures and specialty oncology consultations, and with facilitating a multidisciplinary thoracic oncology tumor board. OBJECTIVE: To test the hypothesis that nurse navigation would improve the timeliness of and access to diagnostic medical services among men and women with newly diagnosed lung cancer. METHODS: A conducted a retrospective review of 460 patients with lung cancer to evaluate access to care and the timeliness of the care received in the non navigated and nurse-navigated cohorts. RESULTS: During December 2009-September 2013, the time between the suspicion of cancer on chest X-ray to treatment was 64 days. During October 2013-March 2014, the nurse navigator helped reduce that timespan to 45 days (?? < .001). LIMITATIONS: Long-term follow-up on clinical outcomes remains premature. CONCLUSION: This finding attests to the successful implementation of nurse navigation to improve access and timeliness of lung cancer care in a community oncology practice. PMID- 26270522 TI - Measuring end-of-life care in oncology practices: learning from the care of the dying. AB - BACKGROUND: There is increased interest among oncology and palliative professionals in providing appropriately timed hospice services for cancer patients. End of life (EoL) metrics have been included in oncology quality programs, but accurate EoL data and benchmarks are hard to obtain. OBJECTIVE: To improve EoL care by measuring patterns of care among recently deceased patients. METHODS: Care utilization among deceased patients was analyzed by using software integrated with patient electronic health records. The data was verified by chart review. RESULTS: Of 179 cancer deaths, tumor registry data differed from chart review in 7% of cases with regard to dates and/or location of death. Institutional EoL metrics were significantly affected by a large number of patients (37%) with advanced illnesses who had clinical diagnoses of cancer made at the end of life, but who had not been managed by oncologists. This population of patients who had not been managed by oncologists was older, less likely to use hospice, and more likely to use the intensive care unit than were oncologist managed cancer patients. Among the patients of individual oncologists, the median stay in hospice ranged from 6-28 days. Data collection and chart review took an average of 27 minutes per case with combined efforts by a data analyst and oncology practitioner. LIMITATIONS: Single institution with comprehensive electronic medical record; some patients were treated outside of the system. CONCLUSION: Acquiring accurate data on EoL metrics is time consuming. Compared with chart review, other data sources have inaccuracies and include some patients who have not been managed by oncologists. Accurate attribution to individual physicians requires chart review by an experienced clinician. PMID- 26270523 TI - Isolated splenic metastasis in a patient with two distinct genitourinary malignancies. AB - Splenic metastasis is rare, occurring in 2.3%- 7.1% of cases, of which 95% are carcinomas.1 The lung is the most common primary tumor site (21% of cases), followed by the gastrointestinal system, breast, ovaries, and skin. In a retrospective study evaluating the clinical and pathological impact of splenic metastases during a 25-year period in China, it was found that about 5.3% of metastases were isolated splenic metastasis.2 Isolated splenic metastasis from kidney cancer is very rare and is often an incidental finding. Here we report a case with isolated splenic metastasis in a patient with both primary renal cell carcinoma and prostate cancer, which turned out to be metastatic renal cell carcinoma in the spleen. PMID- 26270524 TI - Chelsea team doctor acted with "integrity and professionalism," says medical body. PMID- 26270525 TI - Effect of Simulated Microgravity on Human Brain Gray Matter and White Matter- Evidence from MRI. AB - BACKGROUND: There is limited and inconclusive evidence that space environment, especially microgravity condition, may affect microstructure of human brain. This experiment hypothesized that there would be modifications in gray matter (GM) and white matter (WM) of the brain due to microgravity. METHOD: Eighteen male volunteers were recruited and fourteen volunteers underwent -6 degrees head-down bed rest (HDBR) for 30 days simulated microgravity. High-resolution brain anatomical imaging data and diffusion tensor imaging images were collected on a 3T MR system before and after HDBR. We applied voxel-based morphometry and tract based spatial statistics analysis to investigate the structural changes in GM and WM of brain. RESULTS: We observed significant decreases of GM volume in the bilateral frontal lobes, temporal poles, parahippocampal gyrus, insula and right hippocampus, and increases of GM volume in the vermis, bilateral paracentral lobule, right precuneus gyrus, left precentral gyrus and left postcentral gyrus after HDBR. Fractional anisotropy (FA) changes were also observed in multiple WM tracts. CONCLUSION: These regions showing GM changes are closely associated with the functional domains of performance, locomotion, learning, memory and coordination. Regional WM alterations may be related to brain function decline and adaption. Our findings provide the neuroanatomical evidence of brain dysfunction or plasticity in microgravity condition and a deeper insight into the cerebral mechanisms in microgravity condition. PMID- 26270527 TI - Correction: A Developmental Stage-Specific Switch from DAZL to BOLL Occurs during Fetal Oogenesis in Humans, but Not Mice. PMID- 26270526 TI - Hepatomegaly and Liver Dysfunction in a 15-Year-Old Girl With Type 1 Diabetes Mellitus. PMID- 26270528 TI - Chilaiditi's sign secondary to Richter's hernia or Chilaiditi's syndrome? AB - Chilaiditi's sign and syndrome seem similar but are actually different entities, difficult to distinguish from each other. A 60-year-old female presented with a clinical scenario of intestinal obstruction, which was thought to be Chilaiditi's syndrome because of the unusual impression of gas under the diaphragm, but was confirmed as Chilaiditi's sign after laparotomy. The interposition of dilated small bowel loops below the diaphragm due to distal obstruction somewhere else can also produce a Chilaiditi's sign. PMID- 26270529 TI - Expression and Functional Analysis of WRKY Transcription Factors in Chinese Wild Hazel, Corylus heterophylla Fisch. AB - Plant WRKY transcription factors are known to regulate various biotic and abiotic stress responses. In this study we identified a total of 30 putative WRKY unigenes in a transcriptome dataset of the Chinese wild Hazel, Corylus heterophylla, a species that is noted for its cold tolerance. Thirteen full length of these ChWRKY genes were cloned and found to encode complete protein sequences, and they were divided into three groups, based on the number of WRKY domains and the pattern of zinc finger structures. Representatives of each of the groups, Unigene25835 (group I), Unigene37641 (group II) and Unigene20441 (group III), were transiently expressed as fusion proteins with yellow fluorescent fusion protein in Nicotiana benthamiana, where they were observed to accumulate in the nucleus, in accordance with their predicted roles as transcriptional activators. An analysis of the expression patterns of all 30 WRKY genes revealed differences in transcript abundance profiles following exposure to cold, drought and high salinity conditions. Among the stress-inducible genes, 23 were up regulated by all three abiotic stresses and the WRKY genes collectively exhibited four different patterns of expression in flower buds during the overwintering period from November to April. The organ/tissue related expression analysis showed that 18 WRKY genes were highly expressed in stem but only 2 (Unigene9262 and Unigene43101) were greatest in male anthotaxies. The expression of Unigene37641, a member of the group II WRKY genes, was substantially up-regulated by cold, drought and salinity treatments, and its overexpression in Arabidopsis thaliana resulted in better seedling growth, compared with wild type plants, under cold treatment conditions. The transgenic lines also had exhibited higher soluble protein content, superoxide dismutase and peroxidase activiety and lower levels of malondialdehyde, which collectively suggets that Unigene37641 expression promotes cold tolerance. PMID- 26270530 TI - Clopidogrel and Aspirin versus Aspirin Alone for Stroke Prevention: A Meta Analysis. AB - BACKGROUND AND PURPOSE: Antiplatelet therapy is widely used for the primary or secondary prevention of stroke. Drugs like clopidogrel have emerged as alternatives for traditional antiplatelet therapy, and dual therapy with clopidogrel and aspirin is of particular interest. We conducted this meta analysis to systematically review studies about dual therapy comparing monotherapy with aspirin alone. METHODS: Randomized controlled trials were searched in PubMed (1966-May, 2015), EMBASE (1947-May, 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (1948-May, 2015), WHO International Clinical Trial (ICTRP) (2004-May, 2015), China Biology Medicine disc (CBM disc) (1978-May, 2015) and were included into the final analysis according to the definite inclusion criteria mentioned in the study selection section. Risk ratio (RR) was pooled with 95% confidence interval (CI) for dichotomous data. The heterogeneity was considered significant if the chi2 test was significant (P value < 0.10) or the I2 > 50.00%. Subgroup analyses were carried out on the long and short time periods, the race and region. RESULTS: We included 5 studies involving 24,084 patients. A pooled analysis showed that dual therapy with clopidogrel and aspirin had a lower stroke incidence than monotherapy in both the short term and long term (RR = 0.69, 95% CI: 0.59-0.82, P <0.05; RR = 0.84, 95% CI: 0.72-0.98, P = 0.03, respectively). With regard to safety, dual therapy had a higher risk of bleeding than monotherapy for both periods (RR = 1.51, 95% CI: 1.03-2.23, P = 0.04; RR = 1.54, 95% CI: 1.32-1.79, P<0.05, respectively). CONCLUSIONS: Dual therapy with clopidogrel and aspirin could be a preferable choice to prevent stroke in patients who have had a previous stroke or transient ischemic attack, as well as those who are at high risk for stroke. And the effect of dual therapy seems to be more obvious for short-term. However, it is associated with a higher risk of bleeding. PMID- 26270531 TI - Influence of Urbanization on Body Size, Condition, and Physiology in an Urban Exploiter: A Multi-Component Approach. AB - Consistent expanding urbanization dramatically transforms natural habitats and exposes organisms to novel environmental challenges, often leading to reduced species richness and diversity in cities. However, it remains unclear how individuals are affected by the urban environment and how they can or cannot adjust to the specific characteristics of urban life (e.g. food availability). In this study, we used an integrative multi-component approach to investigate the effects of urbanization on the nutritional status of house sparrows (Passer domesticus). We assessed several morphological and physiological indices of body condition in both juveniles (early post-fledging) and breeding adults from four sites with different levels of urbanization in France, Western Europe. We found that sparrows in more urbanized habitats have reduced body size and body mass compared to their rural conspecifics. However, we did not find any consistent differences in a number of complementary indices of condition (scaled mass index, muscle score, hematocrit, baseline and stress-induced corticosterone levels) between urban and rural birds, indicating that urban sparrows may not be suffering nutritional stress. Our results suggest that the urban environment is unlikely to energetically constrain adult sparrows, although other urban-related variables may constrain them. On the other hand, we found significant difference in juvenile fat scores, suggesting that food types provided to young sparrows differed highly between habitats. In addition to the observed smaller size of urban sparrows, these results suggest that the urban environment is inadequate to satisfy early-life sparrows' nutritional requirements, growth, and development. The urban environment may therefore have life-long consequences for developing birds. PMID- 26270532 TI - Development and Characterization of Probe-Based Real Time Quantitative RT-PCR Assays for Detection and Serotyping of Foot-And-Mouth Disease Viruses Circulating in West Eurasia. AB - Rapid and accurate diagnosis of foot-and-mouth disease (FMD) and virus serotyping are of paramount importance for control of this disease in endemic areas where vaccination is practiced. Ideally this virus characterization should be achieved without the need for virus amplification in cell culture. Due to the heterogeneity of FMD viruses (FMDVs) in different parts of the world, region specific diagnostic tests are required. In this study, hydrolysable probe-based real time reverse transcription quantitative polymerase chain reaction (RT-qPCR) assays were developed for specific detection and serotyping of the FMDVs currently circulating in West Eurasia. These assays were evaluated, in parallel with pan-FMDV diagnostic assays and earlier serotype-specific assays, using field samples originating from Pakistan and Afghanistan containing FMD viruses belonging to different sublineages of O-PanAsia, A-Iran05 and Asia-1 (Group-II and Group-VII (Sindh-08)). In addition, field samples from Iran and Bulgaria, containing FMDVs belonging to the O-PanAsiaANT-10 sublineage were also tested. Each of the three primer/probe sets was designed to be specific for just one of the serotypes O, A and Asia-1 of FMDV and detected the RNA from the target viruses with cycle threshold (CT) values comparable with those obtained with the serotype-independent pan-FMDV diagnostic assays. No cross-reactivity was observed in these assays between the heterotypic viruses circulating in the region. The assays reported here have higher diagnostic sensitivity (100% each for serotypes O and Asia-1, and 92% [95% CI = 81.4-100%] for serotype A positive samples) and specificity (100% each for serotypes O, A and Asia-1 positive samples) for the viruses currently circulating in West Eurasia compared to the serotyping assays reported earlier. Comparisons of the sequences of the primers and probes used in these assays and the corresponding regions of the circulating viruses provided explanations for the poor recognition of some of the viruses by the earlier assays. These new assays should help in the early detection and typing of serotype O, A and Asia-1 FMDVs circulating in West Eurasia to enable improved disease control. PMID- 26270533 TI - Assessment of the Impact of Potential Tetracycline Exposure on the Phenotype of Aedes aegypti OX513A: Implications for Field Use. AB - BACKGROUND: Aedes aegypti is the primary vector of dengue fever, a viral disease which has an estimated incidence of 390 million infections annually. Conventional vector control methods have been unable to curb the transmission of the disease. We have previously reported a novel method of vector control using a tetracycline repressible self-limiting strain of Ae. aegypti OX513A which has achieved >90% suppression of wild populations. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the impact of tetracycline and its analogues on the phenotype of OX513A from the perspective of possible routes and levels of environmental exposure. We determined the minimum concentration of tetracycline and its analogues that will allow an increased survivorship and found these to be greater than the maximum concentration of tetracyclines found in known Ae. aegypti breeding sites and their surrounding areas. Furthermore, we determined that OX513A parents fed tetracycline are unable to pre-load their progeny with sufficient antidote to increase their survivorship. Finally, we studied the changes in concentration of tetracycline in the mass production rearing water of OX513A and the developing insect. CONCLUSION/SIGNIFICANCE: Together, these studies demonstrate that potential routes of exposure of OX513A individuals to tetracycline and its analogues in the environment are not expected to increase the survivorship of OX513A. PMID- 26270534 TI - Modulation of the Activity of Mycobacterium tuberculosis LipY by Its PE Domain. AB - Mycobacterium tuberculosis harbors over 160 genes encoding PE/PPE proteins, several of which have roles in the pathogen's virulence. A number of PE/PPE proteins are secreted via Type VII secretion systems known as the ESX secretion systems. One PE protein, LipY, has a triglyceride lipase domain in addition to its PE domain. LipY can regulate intracellular triglyceride levels and is also exported to the cell wall by one of the ESX family members, ESX-5. Upon export, LipY's PE domain is removed by proteolytic cleavage. Studies using cells and crude extracts suggest that LipY's PE domain not only directs its secretion by ESX-5, but also functions to inhibit its enzymatic activity. Here, we attempt to further elucidate the role of LipY's PE domain in the regulation of its enzymatic activity. First, we established an improved purification method for several LipY variants using detergent micelles. We then used enzymatic assays to confirm that the PE domain down-regulates LipY activity. The PE domain must be attached to LipY in order to effectively inhibit it. Finally, we determined that full length LipY and the mature lipase lacking the PE domain (LipYDeltaPE) have similar melting temperatures. Based on our improved purification strategy and activity based approach, we concluded that LipY's PE domain down-regulates its enzymatic activity but does not impact the thermal stability of the enzyme. PMID- 26270535 TI - Green Tea Modulates Cytokine Expression in the Periodontium and Attenuates Alveolar Bone Resorption in Type 1 Diabetic Rats. AB - Diabetes mellitus comprises a heterogeneous group of disorders with the main feature of hyperglycemia. Chronic hyperglycemia increases the severity of periodontal disease via an exacerbated inflammatory response, activated by advanced glycation end products and their receptor, RAGE. Therefore, anti inflammatory agents represent potential inhibitors of this pathological interaction. In particular, green tea has been shown to possess anti-inflammatory properties mediated by its polyphenol content. OBJECTIVES: This study investigated the mechanisms by which green tea attenuates the spontaneous onset of diabetes-induced periodontitis. METHODS: Diabetes was induced in rats via a single intraperitoneal injection of streptozotocin (STZ). Diabetic and control animals were divided into water-treated and green tea-treated subgroups and were analyzed at 15, 30, 60 and 90 days after diabetes induction. Immunohistochemistry was performed to quantitatively evaluate tumor necrosis factor-alpha (TNF-alpha), receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), interleukin-10 (IL-10) and runt-related transcription factor 2 (RUNX-2) expression in serial sections of each hemimaxilla. Morphometric measurements of the distance from the cementum-enamel junction (CEJ) of the superior distal root of the first molar to the alveolar bone crest (ABC) were performed to assess bone loss. RESULTS: Diabetes resulted in significant bone loss and alterations in the number of cells that stained positive for inflammatory mediators. In the diabetic rats treated with green tea, we observed a decreased number of cells expressing RANKL and TNF-alpha compared with that observed in the diabetic rats treated with water. Additionally, green tea increased the numbers of cells that stained positive for OPG, RUNX-2 and IL-10 in the diabetic rats. CONCLUSION: Green tea intake reduces expression of the pro-inflammatory cytokine TNF-alpha and the osteoclastogenic mediator RANKL to normal levels while increasing expression of the anti-inflammatory cytokine IL-10, the osteogenesis-related factor RUNX-2 and the anti-osteoclastogenic factor OPG. Therefore, green tea represents a potential therapeutic agent for the treatment of diabetes-related periodontal disease. PMID- 26270537 TI - Statistical Mechanics of Zooplankton. AB - Statistical mechanics provides the link between microscopic properties of many particle systems and macroscopic properties such as pressure and temperature. Observations of similar "microscopic" quantities exist for the motion of zooplankton, as well as many species of other social animals. Herein, we propose to take average squared velocities as the definition of the "ecological temperature" of a population under different conditions on nutrients, light, oxygen and others. We test the usefulness of this definition on observations of the crustacean zooplankton Daphnia pulicaria. In one set of experiments, D. pulicaria is infested with the pathogen Vibrio cholerae, the causative agent of cholera. We find that infested D. pulicaria under light exposure have a significantly greater ecological temperature, which puts them at a greater risk of detection by visual predators. In a second set of experiments, we observe D. pulicaria in cold and warm water, and in darkness and under light exposure. Overall, our ecological temperature is a good discriminator of the crustacean's swimming behavior. PMID- 26270536 TI - Innate Multigene Family Memories Are Implicated in the Viral-Survivor Zebrafish Phenotype. AB - Since adaptive features such as memory were discovered in mammalian innate immunity, interest in the immunological status of primitive vertebrates after infections has grown. In this context, we used zebrafish (Danio rerio), a primitive vertebrate species suited to molecular and genetic studies to explore transcriptional memories of the immune system in long-term survivors of viral haemorrhagic septicemia virus infections. Immune-gene targeted microarrays designed in-house, multipath genes, gene set enrichment, and leading-edge analysis, reveal unexpected consistent correlations between the viral-survivor phenotype and several innate multigene families. Thus, here we describe in survivors of infections the upregulation of the multigene family of proteasome subunit macropains, zebrafish-specific novel gene sets, mitogen activated protein kinases, and epidermal growth factor. We also describe the downregulation of the multigene families of c-reactive proteins, myxovirus-induced proteins and novel immunoglobulin-type receptors. The strength of those immunological memories was reflected by the exceptional similarity of the transcriptional profiles of survivors before and after re-infection compared with primary infected fish. On the other hand, the high levels of neutralizing antibodies in the blood plasma of survivors contrasted with the depletion of transcripts specific for most cell types present in lymphoid organs. Therefore, long-term survivors maintained unexpected molecular/cellular memories of previous viral encounters by modulating the expression levels of innate multigene families as well as having specific adaptive antibodies. The implications of the so-called "trained immunity" for future research in this field are also discussed. PMID- 26270539 TI - Using Dynamic Multi-Task Non-Negative Matrix Factorization to Detect the Evolution of User Preferences in Collaborative Filtering. AB - Predicting what items will be selected by a target user in the future is an important function for recommendation systems. Matrix factorization techniques have been shown to achieve good performance on temporal rating-type data, but little is known about temporal item selection data. In this paper, we developed a unified model that combines Multi-task Non-negative Matrix Factorization and Linear Dynamical Systems to capture the evolution of user preferences. Specifically, user and item features are projected into latent factor space by factoring co-occurrence matrices into a common basis item-factor matrix and multiple factor-user matrices. Moreover, we represented both within and between relationships of multiple factor-user matrices using a state transition matrix to capture the changes in user preferences over time. The experiments show that our proposed algorithm outperforms the other algorithms on two real datasets, which were extracted from Netflix movies and Last.fm music. Furthermore, our model provides a novel dynamic topic model for tracking the evolution of the behavior of a user over time. PMID- 26270541 TI - A weekly speech and language therapy service for head and neck radiotherapy patients during treatment: maximizing accessibility and efficiency. AB - BACKGROUND: Our hospital did not provide a weekly speech and language therapy (SLT) service for head and neck cancer patients during radiotherapy treatment. SLT is recommended in the international guidelines, but many centers do not offer this service. In the case of our hospital, SLT was not provided because there were no funds to cover the costs of additional staff. OBJECTIVES: To create a new service model within a multidisciplinary setting to comply with the international SLT guidelines and without increasing staff. We aimed to measure the accessibility and efficiency of a new model of service delivery at our center both for patients and for the service. METHODS: 79 patients were recruited for the study. We followed 1 group of patients (n = 29; observation group) throughout their treatment for 6 weeks to establish if there was a clinical need to offer SLT at the treatment center. A second group of patients (n = 50; intervention group) received a weekly SLT review at the treatment center throughout their radiotherapy. Data collected at the tertiary cancer center for 6 months included: age, gender, tumor site and size, treatment modality, swallowing outcomes, communication outcomes, patient satisfaction, multidisciplinary team feedback, and time efficiency. The observation group did not participate in the intervention group because the data was collected between 2 different groups of participants. However, all participants were referred to their local SLT service at the end of their treatment if that was clinically indicated, regardless of the group they had been in. RESULTS: The proportion of patients accessing SLT services during treatment and the time efficiency of the service were both improved with this model of delivery. The service's compliance with international guidelines was met. More patients continued with oral intake during their treatment at our center with the new service. Improvements were also reported in communication clarity and communication confidence in the same group. CONCLUSION: Offering head and neck cancer patients SLT at the same time and place as their radiotherapy treatment improves patient outcomes and increases SLT efficiencies. As this was not a treatment study, further clinical trials are required with regards to functional outcomes. PMID- 26270538 TI - A Comparative Metabolomic Evaluation of Behcet's Disease with Arthritis and Seronegative Arthritis Using Synovial Fluid. AB - Behcet's disease (BD) with arthritis is often confused with seronegative arthritis (SNA) because of shared clinical symptoms and the lack of definitive biomarkers for BD. To investigate possible metabolic patterns and potential biomarkers of BD with arthritis, metabolomic profiling of synovial fluid (SF) from 6 patients with BD with arthritis and 18 patients with SNA was performed using gas chromatography/time-of-flight mass spectrometry in conjunction with univariate and multivariate statistical analyses. A total of 123 metabolites were identified from samples. Orthogonal partial least square-discriminant analysis showed clear discrimination between BD with arthritis and SNA. A set of 11 metabolites were identified as potential biomarkers for BD using variable importance for projection values and the Wilcoxon-Mann-Whitney test. Compared with SNA, BD with arthritis exhibited relatively high levels of glutamate, valine, citramalate, leucine, methionine sulfoxide, glycerate, phosphate, lysine, isoleucine, urea, and citrulline. There were two markers identified, elevated methionine sulfoxide and citrulline, that were associated with increased oxidative stress, providing a potential link to BD-associated neutrophil hyperactivity. Glutamate, citramalate, and valine were selected and validated as putative biomarkers for BD with arthritis (sensitivity, 100%; specificity, 61.1%). This is the first report to present potential biomarkers from SF for discriminating BD with arthritis from SNA. The metabolomics of SF may be helpful in searching for potential biomarkers and elucidating the clinicopathogenesis of BD with arthritis. PMID- 26270540 TI - Health care expenditures associated with depression in adults with cancer. AB - BACKGROUND: The rates of depression in adults with cancer have been reported as high as 38%-58%. How depression affects overall health care expenditures in individuals with cancer is an under-researched area. OBJECTIVE: To estimate excess average total health care expenditures associated with depression in adults with cancer by comparing those with and without depression after controlling for demographic, socioeconomic, access to care, and other health status variables. METHODS: Cross-sectional data on 4,766 adult survivors of cancer from 2006-2009 of the nationally representative household survey, Medical Expenditure Panel Survey (MEPS), were used. The patients were older than 21 years. Cancer and depression were identified from the patients' medical conditions files. Dependent variables consisted of total, inpatient, outpatient, emergency department, prescription drugs, and other expenditures. Ordinary least square (OLS) on logged dollars and generalized linear models with log-link function were performed. All analyses (SAS 9.3 and STATA12) accounted for the complex survey design of the MEPS. RESULTS: Overall, 14% of individuals with cancer reported having depression. In those with cancer and depression, the average annual health care expenditures were $18,401 compared with $12,091 in those without depression. After adjusting for demographic, socioeconomic, access to care, and other health status variables, those with depression had about 31.7% greater total expenditures compared with those without depression. Total, outpatient, and prescription expenditures were higher in individuals with depression than in those without depression. Individuals with cancer and depression were significantly more likely to use emergency departments (adjusted odds ratio, 1.46) compared with their counterparts without depression. LIMITATIONS: Cancer patients who died during the reporting year were excluded. The financial burden of depression may have been underestimated because the costs of end-of-life care are high. The burden for each cancer type was not analyzed because of the small sample size. CONCLUSION: In adults with cancer, those with depression had higher health care utilization and expenditures compared with those without depression. FUNDING/SPONSORSHIP: One author was partially supported by the National Institute of General Medical Sciences, U54GM104942. PMID- 26270542 TI - Inflammatory metastatic breast cancer with gallbladder metastasis: an incidental finding. AB - Breast cancer is the most frequently diagnosed cancer in women, with an estimated 231,840 new cases representing 14.0% of all new cancer cases in the United States in 2015. Early screening and modern techniques of imaging and diagnosis have led to a significant improvement in detecting early-stage breast cancers and to a decrease in the incidence of metastatic breast cancer (MBC). About 20%-30% of patients who are initially diagnosed with an early-stage, nonmetastatic breast cancer will subsequently develop a distant metastatic disease. Between 6%-10% of the new breast cancer cases present initially as stage IV, referred to as de novo MBC. The most common sites of breast cancer metastases are lymph nodes, chest wall, skeleton, lung, skin, and the central nervous system (CNS). Lobular carcinoma, in particular, may metastasize to the gastrointestinal tract, peritoneum, and retroperitoneum. Gallbladder metastasis from breast cancer is very rare, and only 15-20 cases have been reported in the literature. Most of those cases have been associated particularly with a lobular histology. We report an additional rare case of MBC to the gallbladder, but with a ductal histology. PMID- 26270543 TI - Correction: Striatal Dopamine D2/3 Receptor Availability in Treatment Resistant Depression. PMID- 26270544 TI - The Clinical Utility of SUDOSCAN in Chronic Kidney Disease in Chinese Patients with Type 2 Diabetes. AB - There are gaps between recommendations on regular screening for diabetic kidney disease (DKD) and clinical practice especially in busy and low resource settings. SUDOSCAN (Impeto Medical, Paris, France) is a non-invasive technology for assessing sudomotor function using reverse iontophoresis and chronoamperometry which detects abnormal sweat gland function. Vasculopathy and neuropathy share common risk factors and we hypothesized that SUDOSCAN may be used to detect chronic kidney disease (CKD). Between 2012 and 2013, SUDOSCAN was performed in a consecutive cohort of 2833 Hong Kong Chinese adults with type 2 diabetes. Chronic kidney disease was defined as estimated glomerular filtration rate <60 ml/min/1.73m2. In this cross-sectional cohort (mean age 58.6+/-9.5 years, 55.7% male, median disease duration 8 [interquartile range 3-14] years), 5.8% had CKD. At a cut-off SUDOSCAN-DKD score of 53, the test had sensitivity of 76.7%, specificity of 63.4% and positive likelihood ratio of 2.1 to detect CKD. The area under receiver operating characteristic curve for CKD was 0.75 (95% confidence interval 0.72-0.79). Patients without CKD but low score had worse risk factors and complications than those with high score. We conclude that SUDOSCAN may be used to detect patients at risk of impaired renal function as part of a screening program in Chinese population, especially in outreach or low resource settings. PMID- 26270545 TI - Mission Indradhanush makes vaccination progress in India. PMID- 26270546 TI - Correction: A Nationwide Study of Norwegian Patients with Hereditary Angioedema with C1 Inhibitor Deficiency Identified Six Novel Mutations in SERPING1. PMID- 26270548 TI - Positive Selection on Loci Associated with Drug and Alcohol Dependence. AB - Much of the evolution of human behavior remains a mystery, including how certain disadvantageous behaviors are so prevalent. Nicotine addiction is one such phenotype. Several loci have been implicated in nicotine related phenotypes including the nicotinic receptor gene clusters (CHRNs) on chromosomes 8 and 15. Here we use 1000 Genomes sequence data from 3 populations (Africans, Asians and Europeans) to examine whether natural selection has occurred at these loci. We used Tajima's D and the integrated haplotype score (iHS) to test for evidence of natural selection. Our results provide evidence for strong selection in the nicotinic receptor gene cluster on chromosome 8, previously found to be significantly associated with both nicotine and cocaine dependence, as well as evidence selection acting on the region containing the CHRNA5 nicotinic receptor gene on chromosome 15, that is genome wide significant for risk for nicotine dependence. To examine the possibility that this selection is related to memory and learning, we utilized genetic data from the Collaborative Studies on the Genetics of Alcoholism (COGA) to test variants within these regions with three tests of memory and learning, the Wechsler Adult Intelligence Scale (WAIS) Block Design, WAIS Digit Symbol and WAIS Information tests. Of the 17 SNPs genotyped in COGA in this region, we find one significantly associated with WAIS digit symbol test results. This test captures aspects of reaction time and memory, suggesting that a phenotype relating to memory and learning may have been the driving force behind selection at these loci. This study could begin to explain why these seemingly deleterious SNPs are present at their current frequencies. PMID- 26270547 TI - How Can We Improve the Detection of Alpha1-Antitrypsin Deficiency? AB - The Z deficiency in alpha1-antitrypsin (A1ATD) is an under-recognized condition. Alpha1-antitrypsin (A1AT) is the main protein in the alpha1-globulin fraction of serum protein electrophoresis (SPE); however, evaluation of the alpha1-globulin protein fraction has received very little attention. Serum Z-type A1AT manifests in polymeric forms, but their interference with quantitative immunoassays has not been reported. Here, 214 894 samples were evaluated by SPE at the G. Fracastoro Hospital of Verona, Italy. Patients with an A1AT level <= 0.92 g/L were recalled to complete A1ATD diagnosis. In parallel, to qualitatively and quantitatively characterize A1AT, sera samples from 10 PiZZ and 10 PiMM subjects obtained at the National Institute of Tuberculosis and Lung Diseases in Warsaw, Poland, were subjected to non-denaturing 7.5% PAGE and 7.5% SDS-PAGE followed by Western blot. Moreover, purified A1AT was heated at 60 degrees C and analyzed by a non denaturing PAGE and 4-15% gradient SDS-PAGE followed by Western blot as well as by isolelectrofocusing and nephelometry. A total of 966 samples manifested percentages <= 2.8 or a double band in the alpha1-zone. According to the nephelometry data, 23 samples were classified as severe (A1AT <= 0.49 g/L) and 462 as intermediate (A1AT >0.49<= 1.0 g/L) A1ATD. Twenty subjects agreed to complete the diagnosis and an additional 21 subjects agreed to family screening. We detected 9 cases with severe and 26 with intermediate A1ATD. Parallel experiments revealed that polymerization of M-type A1AT, when measured by nephelometry or isolelectrofocusing, yields inaccurate results, leading to the erroneous impression that it was Z type and not M-type A1AT. We illustrate the need for confirmation of Z A1AT values by "state of the art" method. Clinicians should consider a more in-depth investigation of A1ATD in patients when they exhibit serum polymers and low alpha1-globulin protein levels by SPE. PMID- 26270549 TI - Selection of Fusion Levels Using the Fulcrum Bending Radiograph for the Management of Adolescent Idiopathic Scoliosis Patients with Alternate Level Pedicle Screw Strategy: Clinical Decision-making and Outcomes. AB - OBJECTIVE: Selecting fusion levels based on the Luk et al criteria for operative management of thoracic adolescent idiopathic scoliosis (AIS) with hook and hybrid systems yields acceptable curve correction and balance parameters; however, it is unknown whether utilizing a purely pedicle screw strategy is effective. Utilizing the fulcrum bending radiographic (FBR) to assess curve flexibility to select fusion levels, the following study assessed the efficacy of pedicle screw fixation with alternate level screw strategy (ALSS) for thoracic AIS. METHODS: A retrospective study with prospective radiographic data collection/analyses (preoperative, postoperative 1-week and minimum 2-year follow-up) of 28 operative thoracic AIS patients undergoing ALSS was performed. Standing coronal/sagittal and FBR Cobb angles, FBR flexibility, fulcrum bending correction index (FBCI), trunkal shift, radiographic shoulder height (RSH), and list were assessed on x rays. Fusion level selection was based on the Luk et al criteria and compared to conventional techniques. RESULTS: In the primary curve, the mean preoperative and postoperative 1 week and last follow-up standing coronal Cobb angles were 59.9, 17.2 and 20.0 degrees, respectively. Eighteen patients (64.3%) had distal levels saved (mean: 1.6 levels) in comparison to conventional techniques. Mean immediate and last follow-up FBCIs were 122.6% and 115.0%, respectively. Sagittal alignment did not statistically differ between any assessment intervals (p>0.05). A decrease in trunkal shift was noted from preoperative to last follow-up (p = 0.003). No statistically significant difference from preoperative to last follow up was noted in RSH and list (p>0.05). No "add-on" of other vertebra or decompensation was noted and all patients achieved fusion. CONCLUSIONS: This is the first report to note that using the FBR for decision-making in selecting fusion levels in thoracic AIS patients undergoing management with pedicle screw constructs (e.g. ALSS) is a cost-effective strategy that can achieve clinically relevant deformity correction that is maintained and without compromising fusion levels. PMID- 26270550 TI - Environmental Controls on River Assemblages at the Regional Scale: An Application of the Elements of Metacommunity Structure Framework. AB - Understanding factors that structure regional biodiversity is important for linking ecological and biogeographic processes. Our objective was to explore regional patterns in riverine benthic invertebrate assemblages in relation to their broad positioning along the river network and examine differences in composition, biodiversity (alpha and beta diversity), and environmental drivers. We up-scaled methods used to examine patterns in metacommunity structure (Elements of Metacommunity Structure framework) to examine faunal distribution patterns at the regional extent for 168 low-mountain stream invertebrate assemblages in central Germany. We then identified the most influential environmental factors using boosted regression trees. Faunal composition patterns were compartmentalised (Clementsian or quasi-Clementsian), with little difference from headwaters to large rivers, potentially reflecting the regional scale of the study, by crossing major catchment boundaries and incorporating different species pools. While idealised structures did not vary, environmental drivers of composition varied considerably between river sections and with alpha diversity. Prediction was substantially weaker, and the importance of space was greater, in large rivers compared to other sections suggesting a weakening in species sorting downstream. Further, there was a stronger transition in composition than for alpha diversity downstream. The stronger links with regional faunal composition than with richness further emphasises the importance of considering the alternative ways in which anthropogenic stressors are operating to affect biodiversity patterns. Our approach allowed bridging the gap between local (or metacommunity) and regional scales, providing key insights into drivers of regional biodiversity patterns. PMID- 26270554 TI - Molecular Recognition with Microporous Multilayer Films Prepared by Layer-by Layer Assembly of Pillar[5]arenes. AB - Pillar[5]arene-based multilayer films are constructed by layer-by-layer assembly with consecutive adsorption of cationic and anionic pillar[5]arenes. The films have active pores that allow shape-selective uptake of dinitrobenzene isomers: the film adsorbs para-dinitrobenzene, but not ortho- and meta-dinitrobenzene. The ability of the film to adsorb para-dinitrobenzene is result of the surface electrostatic potential: para-dinitrobenzene adsorbs on films with a positive surface, but not on films with a negative surface. The adsorbed amount of para dinitrobenzene exponentially increases with increasing number of deposited layers. PMID- 26270551 TI - Chilling- and Freezing-Induced Alterations in Cytosine Methylation and Its Association with the Cold Tolerance of an Alpine Subnival Plant, Chorispora bungeana. AB - Chilling (0-18 degrees C) and freezing (<0 degrees C) are two distinct types of cold stresses. Epigenetic regulation can play an important role in plant adaptation to abiotic stresses. However, it is not yet clear whether and how epigenetic modification (i.e., DNA methylation) mediates the adaptation to cold stresses in nature (e.g., in alpine regions). Especially, whether the adaptation to chilling and freezing is involved in differential epigenetic regulations in plants is largely unknown. Chorispora bungeana is an alpine subnival plant that is distributed in the freeze-thaw tundra in Asia, where chilling and freezing frequently fluctuate daily (24 h). To disentangle how C. bungeana copes with these intricate cold stresses through epigenetic modifications, plants of C. bungeana were treated at 4 degrees C (chilling) and -4 degrees C (freezing) over five periods of time (0-24 h). Methylation-sensitive amplified fragment-length polymorphism markers were used to investigate the variation in DNA methylation of C. bungeana in response to chilling and freezing. It was found that the alterations in DNA methylation of C. bungeana largely occurred over the period of chilling and freezing. Moreover, chilling and freezing appeared to gradually induce distinct DNA methylation variations, as the treatment went on (e.g., after 12 h). Forty-three cold-induced polymorphic fragments were randomly selected and further analyzed, and three of the cloned fragments were homologous to genes encoding alcohol dehydrogenase, UDP-glucosyltransferase and polygalacturonase inhibiting protein. These candidate genes verified the existence of different expressive patterns between chilling and freezing. Our results showed that C. bungeana responded to cold stresses rapidly through the alterations of DNA methylation, and that chilling and freezing induced different DNA methylation changes. Therefore, we conclude that epigenetic modifications can potentially serve as a rapid and flexible mechanism for C. bungeana to adapt to the intricate cold stresses in the alpine areas. PMID- 26270553 TI - Long-term contributions from the diabetes control and complications trial cohort. PMID- 26270555 TI - Nanostructured Ion-Exchange Membranes for Fuel Cells: Recent Advances and Perspectives. AB - Polymer-based materials with tunable nanoscale structures and associated microenvironments hold great promise as next-generation ion-exchange membranes (IEMs) for acid or alkaline fuel cells. Understanding the relationships between nanostructure, physical and chemical microenvironment, and ion-transport properties are critical to the rational design and development of IEMs. These matters are addressed here by discussing representative and important advances since 2011, with particular emphasis on aromatic-polymer-based nanostructured IEMs, which are broadly divided into nanostructured polymer membranes and nanostructured polymer-filler composite membranes. For each category of membrane, the core factors that influence the physical and chemical microenvironments of the ion nanochannels are summarized. In addition, a brief perspective on the possible future directions of nanostructured IEMs is presented. PMID- 26270552 TI - Brain Networks Responsible for Sense of Agency: An EEG Study. AB - BACKGROUND: Self-agency (SA) is a person's feeling that his action was generated by himself. The neural substrates of SA have been investigated in many neuroimaging studies, but the functional connectivity of identified regions has rarely been investigated. The goal of this study is to investigate the neural network related to SA. METHODS: SA of hand movements was modulated with virtual reality. We examined the cortical network relating to SA modulation with electroencephalography (EEG) power spectrum and phase coherence of alpha, beta, and gamma frequency bands in 16 right-handed, healthy volunteers. RESULTS: In the alpha band, significant relative power changes and phase coherence of alpha band were associated with SA modulation. The relative power decrease over the central, bilateral parietal, and right temporal regions (C4, Pz, P3, P4, T6) became larger as participants more effectively controlled the virtual hand movements. The phase coherence of the alpha band within frontal areas (F7-FP2, F7-Fz) was directly related to changes in SA. The functional connectivity was lower as the participants felt that they could control their virtual hand. In the other frequency bands, significant phase coherences were observed in the frontal (or central) to parietal, temporal, and occipital regions during SA modulation (Fz O1, F3-O1, Cz-O1, C3-T4L in beta band; FP1-T6, FP1-O2, F7-T4L, F8-Cz in gamma band). CONCLUSIONS: Our study suggests that alpha band activity may be the main neural oscillation of SA, which suggests that the neural network within the anterior frontal area may be important in the generation of SA. PMID- 26270556 TI - Smokers Show Lower Levels of Psychological Well-Being and Mindfulness than Non Smokers. AB - Mindfulness is defined as "paying attention in a particular way, on purpose, in the present moment, and nonjudgmentally". Mindfulness is associated with positive affect, life satisfaction, self-esteem, lower negative affect and rumination. Conversely, evidence suggests a relationship between nicotine dependence and psychiatric disorders. This study aimed to compare the levels of Mindfulness and Subjective Well-Being (SWB) between smokers and non-smokers. Ninety seven smokers and eighty four non-smokers participated in the study (n = 181). The Five Facet Mindfulness Questionnaire (FFMQ-BR) and the Subjective Well-Being Scale (SWBS) were used. In all the factors of SWBS, the total scores in the FFMQ-BR and in the facets of Observing and Non-Reactivity, the non-smokers scored higher than the smokers. This study suggests that smokers present lower levels of Mindfulness and SWB than non-smokers. Consequently, we propose that Mindfulness-Based Interventions (MBI) may help smokers deal with treatment and abstinence by increasing their level of SWB. PMID- 26270557 TI - Using Skin Markers for Spinal Curvature Quantification in Main Thoracic Adolescent Idiopathic Scoliosis: An Explorative Radiographic Study. AB - BACKGROUND AND PURPOSE: Although the relevance of understanding spinal kinematics during functional activities in patients with complex spinal deformities is undisputed among researchers and clinicians, evidence using skin marker-based motion capture systems is still limited to a handful of studies, mostly conducted on healthy subjects and using non-validated marker configurations. The current study therefore aimed to explore the validity of a previously developed enhanced trunk marker set for the static measurement of spinal curvature angles in patients with main thoracic adolescent idiopathic scoliosis. In addition, the impact of inaccurate marker placement on curvature angle calculation was investigated. METHODS: Ten patients (Cobb angle: 44.4+/-17.7 degrees) were equipped with radio-opaque markers on selected spinous processes and underwent a standard biplanar radiographic examination. Subsequently, radio-opaque markers were replaced with retro-reflective markers and the patients were measured statically using a Vicon motion capture system. Thoracolumbar/lumbar and thoracic curvature angles in the sagittal and frontal planes were calculated based on the centers of area of the vertebral bodies and radio-opaque markers as well as the three-dimensional position of the retro-reflective markers. To investigate curvature angle estimation accuracy, linear regression analyses among the respective parameters were used. The impact of inaccurate marker placement was explored using linear regression analyses among the radio-opaque marker- and spinous process-derived curvature angles. RESULTS AND DISCUSSION: The results demonstrate that curvatures angles in the sagittal plane can be measured with reasonable accuracy, whereas in the frontal plane, angles were systematically underestimated, mainly due to the positional and structural deformities of the scoliotic vertebrae. Inaccuracy of marker placement had a greater impact on thoracolumbar/lumbar than thoracic curvature angles. It is suggested that spinal curvature measurements are included in marker-based clinical gait analysis protocols in order to enable a deeper understanding of the biomechanical behavior of the healthy and pathological spine in dynamic situations as well as to comprehensively evaluate treatment effects. PMID- 26270558 TI - Accuracy of Prehospital Intravenous Fluid Volume Measurement by Emergency Medical Services. AB - Prehospital treatment protocols call for intravenous (IV) fluid for patients with shock, yet the measurement accuracy of administered fluid volume is unknown. The purpose of the current study was to assess the accuracy of documented and self reported fluid volumes administered to medical patients by paramedics during prehospital care. We conducted a pilot, observational study nested within a parent cohort study of prehospital biomarkers in a single EMS agency transporting patients to a tertiary care hospital in Pittsburgh, Pennsylvania over 8 months. Among eligible nontrauma, noncardiac arrest patients, we studied the self reported IV fluid volume on ED arrival by paramedics, documented fluid volume in the EMS record, and compared those to the mass-derived fluid volume. We quantified the absolute error between methods, and determined EMS transport times or initial prehospital systolic blood pressure had any effect on error. We enrolled 50 patients who received prehospital IV fluid and had mass-derived fluid volume measured at ED arrival. Of these, 21 (42%) patients had IV fluid volume subsequently documented in EMS records. The median mass-derived fluid volume was 393 mL [IQR: 264-618 mL]. Mass-derived volume was similar for subjects who did (386 mL, IQR: 271-642 mL) or did not (399 mL, IQR: 253-602) have documented fluid administration (p > 0.05). The median self-reported fluid volume was 250 mL [IQR: 150-500 mL] and did not differ by documentation (p > 0.05). The median absolute error comparing self-reported to mass-derived fluid volume was 109 mL [IQR: 41 205 mL], and less than 250 mL in more than 80% of subjects. The median absolute error comparing documented fluid to mass-derived fluid volume was 142 mL [IQR: 64 265 mL], and was less than 250 mL in 71% of subjects. No difference in absolute error for either self-reported or document fluid volumes were modified by transport time or prehospital systolic blood pressure. Prehospital IV fluid administration is variably documented by EMS, and when recorded is typically within 250 mL of mass-derived fluid volume. KEY WORDS: emergency medical services; prehospital resuscitation; intravenous fluids; fluids. PMID- 26270560 TI - Beckwith-Wiedemann Syndrome Revisited. PMID- 26270562 TI - Gender Nonconforming Children. PMID- 26270561 TI - Dietary Pectin Increases Intestinal Crypt Stem Cell Survival following Radiation Injury. AB - Gastrointestinal (GI) mucosal damage is a devastating adverse effect of radiation therapy. We have recently reported that expression of Dclk1, a Tuft cell and tumor stem cell (TSC) marker, 24h after high dose total-body gamma-IR (TBI) can be used as a surrogate marker for crypt survival. Dietary pectin has been demonstrated to possess chemopreventive properties, whereas its radioprotective property has not been studied. The aim of this study was to determine the effects of dietary pectin on ionizing radiation (IR)-induced intestinal stem cell (ISC) deletion, crypt and overall survival following lethal TBI. C57BL/6 mice received a 6% pectin diet and 0.5% pectin drinking water (pre-IR mice received pectin one week before TBI until death; post-IR mice received pectin after TBI until death). Animals were exposed to TBI (14 Gy) and euthanized at 24 and 84h post-IR to assess ISC deletion and crypt survival respectively. Animals were also subjected to overall survival studies following TBI. In pre-IR treatment group, we observed a three-fold increase in ISC/crypt survival, a two-fold increase in Dclk1+ stem cells, increased overall survival (median 10d vs. 7d), and increased expression of Dclk1, Msi1, Lgr5, Bmi1, and Notch1 (in small intestine) post-TBI in pectin treated mice compared to controls. We also observed increased survival of mice treated with pectin (post-IR) compared to controls. Dietary pectin is a radioprotective agent; prevents IR-induced deletion of potential reserve ISCs; facilitates crypt regeneration; and ultimately promotes overall survival. Given the anti-cancer activity of pectin, our data support a potential role for dietary pectin as an agent that can be administered to patients receiving radiation therapy to protect against radiation-induces mucositis. PMID- 26270564 TI - Lipid peroxidation and antioxidants status in human malignant and non-malignant thyroid tumours. AB - INTRODUCTION: Thyroid epithelial cells produce moderate amounts of reactive oxygen species that are physiologically required for thyroid hormone synthesis. Nevertheless, when they are produced in excessive amounts, they may become toxic. OBJECTIVE: The present study is aimed to compare the lipid peroxidation (LPO), antioxidant enzymes - superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and non-protein thiols (reduced glutathione (GSH)) in human thyroid tissues with malignant and non-malignant disorders. DESIGN AND METHODS: The study used human thyroid tissues and blood samples from 157 women (147 diseased and 10 normal). Thyroid hormones, oxidative stress markers and antioxidants were estimated by standard methods. RESULTS: LPO significantly increased in most of the papillary thyroid carcinoma (PTC: 82.9%) and follicular thyroid adenoma (FTA: 72.9%) tissues, whilst in a majority of nodular goitre (69.2%) and Hashimoto's thyroiditis (HT: 73.7%) thyroid tissues, it remained unaltered. GSH increased in PTC (55.3%), remained unaltered in FTA (97.3%) and all other goiter samples studied. SOD increased in PTC (51.1%) and all other malignant thyroid tissues studied. CAT remained unaltered in PTC (95.7%), FTA (97.3%) and all other non-malignant samples (HT, MNG, TMNG) studied. GPx increased in PTC (63.8%), all other malignant thyroid tissues and remained unaltered in many of the FTA (91.9%) tissues and all other non-malignant samples (HT, MNG, TMNG) studied. CONCLUSIONS: In the case of non-malignant thyroid tumours, the oxidant-antioxidant balance was undisturbed, whilst in malignant tumours the balance was altered, and the change in r value observed in the LPO and SOD pairs between normal and PTC tissues and also in many pairs with multi nodular goitre (MNG)/toxic MNG tissues may be used as a marker to differentiate/detect different malignant/non-malignant thyroid tumours. PMID- 26270566 TI - Formation of Chlorotriophenoxy Radicals from Complete Series Reactions of Chlorotriophenols with H and OH Radicals. AB - The chlorothiophenoxy radicals (CTPRs) are key intermediate species in the formation of polychlorinated dibenzothiophenes/thianthrenes (PCDT/TAs). In this work, the formation of CTPRs from the complete series reactions of 19 chlorothiophenol (CTP) congeners with H and OH radicals were investigated theoretically by using the density functional theory (DFT) method. The profiles of the potential energy surface were constructed at the MPWB1K/6 311+G(3df,2p)//MPWB1K/6-31+G(d,p) level. The rate constants were evaluated by the canonical variational transition-state (CVT) theory with the small curvature tunneling (SCT) contribution at 600-1200 K. The present study indicates that the structural parameters, thermal data, and rate constants as well as the formation potential of CTPRs from CTPs are strongly dominated by the chlorine substitution at the ortho-position of CTPs. Comparison with the study of formation of chlorophenoxy radicals (CPRs) from chlorophenols (CPs) clearly shows that the thiophenoxyl-hydrogen abstraction from CTPs by H is more efficient than the phenoxyl-hydrogen abstraction from CPs by H, whereas the thiophenoxyl-hydrogen abstraction from CTPs by OH is less impactful than the phenoxyl-hydrogen abstraction from CPs by OH. Reactions of CTPs with H can occur more readily than that of CTPs with OH, which is opposite to the reactivity comparison of CPs with H and OH. PMID- 26270567 TI - Asymmetric Intramolecular Conjugate Addition Nitro-Mannich Route to cis-2-Aryl-3 nitrotetrahydroquinolines. AB - Reductive cyclization of 2-iminonitrostyrenes (from the condensation of 2 aminostyrenes with an aldehyde and subsequent nitration of the alkene) using a bifunctional thiourea catalyst and tert-butyl-Hantzsch ester leads to an intramolecular conjugate hydride addition nitro-Mannich reaction to give the corresponding cis-2-aryl-3-nitrotetrahydroquinolines as single diastereoisomers in high yields and enantioselectivities. PMID- 26270563 TI - Heart Rate Variability as an Indicator of Chronic Stress Caused by Lameness in Dairy Cows. AB - Most experimental studies on animal stress physiology have focused on acute stress, while chronic stress, which is also encountered in intensive dairy cattle farming--e.g. in case of lameness--, has received little attention. We investigated heart rate (HR) and heart rate variability (HRV) as indicators of the autonomic nervous system activity and fecal glucocorticoid concentrations as the indicator of the hypothalamic-pituitary-adrenal axis activity in lame (with locomotion scores 4 and 5; n = 51) and non-lame (with locomotion scores 1 and 2; n = 52) Holstein-Friesian cows. Data recorded during the periods of undisturbed lying--representing baseline cardiac activity--were involved in the analysis. Besides linear analysis methods of the cardiac inter-beat interval (time-domain geometric, frequency domain and Poincare analyses) non-linear HRV parameters were also evaluated. With the exception of standard deviation 1 (SD1), all HRV indices were affected by lameness. Heart rate was lower in lame cows than in non-lame ones. Vagal tone parameters were higher in lame cows than in non-lame animals, while indices of the sympathovagal balance reflected on a decreased sympathetic activity in lame cows. All geometric and non-linear HRV measures were lower in lame cows compared to non-lame ones suggesting that chronic stress influenced linear and non-linear characteristics of cardiac function. Lameness had no effect on fecal glucocorticoid concentrations. Our results demonstrate that HRV analysis is a reliable method in the assessment of chronic stress, however, it requires further studies to fully understand the elevated parasympathetic and decreased sympathetic tone in lame animals. PMID- 26270569 TI - Connectivity. AB - PURPOSE OF REVIEW: Connectivity is a technique that uses functional MRI (fMRI) to explore global brain function in healthy and diseased states. Connectivity is now being studied as a part of global brain function in major national and international studies. It is, therefore, timely to review its relevance to anaesthesia. RECENT FINDINGS: Dynamic connectivity in the brain, which transcends anatomical boundaries, links functionally related regions. Clinical manifestations in neuropsychiatric diseases such has Alzheimer's disease and schizophrenia can be explained on the basis of altered connectivity patterns in the brain. Anaesthetic agents primarily disrupt long-range networks and affect the higher order networks linked to cognition causing cognitive unbinding in the brain. Lower-order, basic sensorimotor networks are less sensitive. Normal ageing causes alterations in connectivity that affects the default mode network (DMN) and certain other networks, which in turn impair fluidic measures of brain function such as reaction time, dual task performance and executive function in elderly. SUMMARY: Higher mental function related networks such as the DMN, the executive control network and salience are more sensitive to anaesthesia. In geriatric patients, the DMN is impaired, which affects cognition. Hence, the combined effect of age and anaesthesia in elderly on mental function can cause significant postoperative cognitive impairment. PMID- 26270570 TI - Standard Protocol and Quality Assessment of Soil Phosphorus Speciation by P K Edge XANES Spectroscopy. AB - Phosphorus (P) in soils is most often bound as phosphate to one or more of the following four elements or compounds: calcium, aluminum, iron, and soil organic matter. A promising method for direct P speciation in soils is synchrotron-based X-ray absorption near edge structure (XANES) spectroscopy at the K-edge of P. However, the quality of this method is debated controversially, partly because a standard protocol for reproducible spectrum deconvolution is lacking and minor modifications of the applied deconvolution procedure can lead to considerable changes in the P speciation results. On the basis of the observation that appropriate baseline correction and edge-step normalization are crucial for correct linear combination (LC) fitting results, we established a standard protocol for the deconvolution and LC fitting of P K-edge XANES spectra. We evaluated the quality of LC fits obtained according to this standard protocol with 16 defined dilute (2 mg P g(-1)) ternary mixtures of aluminum phosphate, iron phosphate, hydroxyapatite, and phytic acid in a quartz matrix. The LC fitting results were compared with the contribution of the different P compounds to total P in the various mixtures. Compared to using a traditional LC fitting procedure, our standard protocol reduced the fitting error by 6% (absolute). However, P portions smaller than 5% should be confirmed with other methods or excluded from the P speciation results. A publicly available database of P K-edge XANES reference spectra was initiated. PMID- 26270568 TI - Fragment Binding Can Be Either More Enthalpy-Driven or Entropy-Driven: Crystal Structures and Residual Hydration Patterns Suggest Why. AB - In lead optimization, small, enthalpically advantaged fragments have been suggested to be superior, as an entropic component will be added inevitably during late-stage optimization. Determination of thermodynamic signatures of weak binding fragments is essential to support the decision-making process, to decide which fragment to take to further optimization. High-resolution crystal structures of six fragments binding to the S1 pocket of thrombin were determined and analyzed with respect to their thermodynamic profile. The two most potent fragments exhibiting an amidine-type scaffold are not the most enthalpic binders; instead a chloro-thiophene fragment binds more enthalpically. Two chemically very similar chloro-aromatic fragments differ strongly in their potency (430 MUM vs 10 mM); their binding modes are related, but the surrounding residual water network differs. The more potent one recruits a water molecule and involves Glu192 in binding, thus succeeding in firmly capping the S1 pocket. Fragments exhibiting a rather perfect solvation pattern in their binding mode also experience the highest potency. PMID- 26270571 TI - Nuclear bioavailability of the glucocorticoid receptor in a pediatric asthma cohort with variable corticosteroid responsiveness. AB - BACKGROUND: Despite the overall effectiveness of glucocorticoids (GCs) in the treatment of asthma, a large proportion of patients do not fully respond to this medication. The objective of the present study was to investigate the potential molecular mechanisms responsible for corticosteroid insensitivity in pediatric asthma. METHODS: Asthmatic children were classified as good (GSR) or poor corticosteroid responders (PSR) based on the changes in pulmonary function following GC treatment. Immortalized B-cells derived from patients at two ends of the spectrum of GC responsiveness (five each) were grown in culture and treated with hydrocortisone (10(-6)M). Baseline and temporal changes in GC receptor (GR) protein and mRNA were evaluated by western blot and quantitative reverse transcription PCR respectively. The effect of GC treatment on GR nuclear levels was assessed by western blots. RESULTS: Cells derived from PSR asthmatics displayed lower GR protein levels when compared to GSR. Moreover, in PSR cells GC induced nuclear translocation of GR was short-lived and homologous downregulation of GR mRNA and protein was faster than in GSR. CONCLUSION: Our data demonstrate the existence of a novel mechanism of GC insensitivity resulting from limited GR nuclear bioavailability as a consequence of decreased baseline GR protein expression and more rapid hormone-induced downregulation. PMID- 26270572 TI - Necrotizing enterocolitis in a mouse model leads to widespread renal inflammation, acute kidney injury, and disruption of renal tight junction proteins. AB - BACKGROUND: Necrotizing enterocolitis (NEC) is a devastating condition affecting premature infants and leads to high mortality and chronic morbidity. Severe form of NEC is associated with acute renal failure, fluid imbalance, hyponatremia, and acidosis. We investigated the effect of NEC on tight junction (TJ) proteins in kidneys using a NEC mouse model to investigate the basis for the observed renal dysfunction. METHODS: NEC was induced in C57BL/6 mice by formula feeding and subjecting them to periods of hypoxia and cold stress. NEC was confirmed by gross and histological examination. We studied various markers of inflammation in kidneys and investigated changes in expression of several TJ proteins and AQP2 using immunofluorecent staining and western blotting. RESULTS: We found markedly increased expression of NFkappaB, TGFbeta, and ERK1/2 along with claudin-1, -2, 3, -4, -8, and AQP-2 in NEC kidneys. The membrane localization of claudin-2 was altered in the NEC kidneys and its immunostaining signal at TJ was disrupted. CONCLUSION: NEC led to a severe inflammatory response not only in the gut but also in the kidneys. NEC increased expression of several TJ proteins and caused disruption of claudin-2 in renal tubules. These observed changes can help explain some of the clinical findings observed in NEC. PMID- 26270565 TI - Scanning for Therapeutic Targets within the Cytokine Network of Idiopathic Inflammatory Myopathies. AB - The idiopathic inflammatory myopathies (IIM) constitute a heterogeneous group of chronic disorders that include dermatomyositis (DM), polymyositis (PM), sporadic inclusion body myositis (IBM) and necrotizing autoimmune myopathy (NAM). They represent distinct pathological entities that, most often, share predominant inflammation in muscle tissue. Many of the immunopathogenic processes behind the IIM remain poorly understood, but the crucial role of cytokines as essential regulators of the intramuscular build-up of inflammation is undisputed. This review describes the extensive cytokine network within IIM muscle, characterized by strong expression of Tumor Necrosis Factors (TNFalpha, LTbeta, BAFF), Interferons (IFNalpha/beta/gamma), Interleukins (IL-1/6/12/15/18/23) and Chemokines (CXCL9/10/11/13, CCL2/3/4/8/19/21). Current therapeutic strategies and the exploration of potential disease modifying agents based on manipulation of the cytokine network are provided. Reported responses to anti-TNFalpha treatment in IIM are conflicting and new onset DM/PM has been described after administration of anti-TNFalpha agents to treat other diseases, pointing to the complex effects of TNFalpha neutralization. Treatment with anti-IFNalpha has been shown to suppress the IFN type 1 gene signature in DM/PM patients and improve muscle strength. Beneficial effects of anti-IL-1 and anti-IL-6 therapy have also been reported. Cytokine profiling in IIM aids the development of therapeutic strategies and provides approaches to subtype patients for treatment outcome prediction. PMID- 26270574 TI - Evaluation of kidney dysfunction and angiotensinogen as an early novel biomarker of intrauterine growth restricted offspring rats. AB - BACKGROUND: Few studies have addressed the growing concerns of chronic kidney diseases in children with intrauterine growth restriction (IUGR). Therefore, the purpose of this study was to evaluate long-term kidney dysfunction and determine if urinary angiotensinogen (AGT) was suitable as a novel early biomarker for kidney dysfunction in IUGR offspring. METHODS: Pregnant rats underwent bilateral uterine artery ligation, and as a control group, sham surgeries were performed. RESULTS: The birth weight was reduced, the urinary AGT to creatinine ratio was significantly higher at week 20, and urinary protein levels were significantly higher at week 32 in IUGR rats than in control rats. On the other hand, the histological findings at week 32 revealed long-term kidney dysfunction, more severe glomerulosclerosis, and greater glomerular diameters in IUGR rats. Moreover, AGT mRNA expression and immunohistological staining were significantly increased in IUGR rats; this suggests that the intrarenal renin-angiotensin system (RAS) contributes to renal dysfunction of IUGR offspring. CONCLUSION: Urinary AGT elevation prior to urinary protein levels suggests that AGT is an early biomarker. At week 32, kidney dysfunction was severe in IUGR rats and intrarenal RAS appeared to be one of the causes. PMID- 26270575 TI - Long-chain polyunsaturated fatty acids attenuate the IL-1beta-induced proinflammatory response in human fetal intestinal epithelial cells. AB - BACKGROUND: Evidence suggests that excessive inflammation of the immature intestine may predispose premature infants to necrotizing enterocolitis (NEC). We investigated the anti-inflammatory effects of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA) in human fetal and adult intestinal epithelial cells (IEC) in primary culture. METHODS: Human fetal IEC in culture were derived from a healthy fetal small intestine (H4) or resected small intestine of a neonate with NEC (NEC-IEC). Intestinal cell lines Caco2 and NCM460 in culture were used as models for mature IEC. IEC in culture were pretreated with 100 umol/l palmitic acid (PAL), DHA, EPA, ARA, or ARA+DHA for 48 h and then stimulated with proinflammatory IL-1beta. RESULTS: DHA significantly attenuated IL-1beta induced proinflammatory IL-8 and IL-6 protein and mRNA in fetal H4, NEC IEC, and mature Caco2, NCM460 IEC, compared to control and PAL treatment. DHA downregulated IL-1R1 (IL-1beta receptor) and NFk beta1 mRNA expression in fetal and adult IEC. ARA had potent anti-inflammatory effects with lower IL-8 and IL-6 (protein and mRNA) in fetal H4 but not in NEC-IEC or adult IEC. CONCLUSION: The present study provides evidence that DHA and ARA may have important anti inflammatory functions for prevention of NEC in premature infants. PMID- 26270573 TI - Low-glycemic index diet may improve insulin sensitivity in obese children. AB - BACKGROUND: A low-glycemic index (GI) diet may be beneficial for weight management due to its effect on insulin metabolism and satiety. METHODS: Obese children aged 9-16 y were randomly assigned either a low-GI diet or a low-fat diet (control group) for 6 mo. Body composition changes were measured by dual energy X-ray absorptiometry and bioelectrical impedance analysis. Insulin sensitivity was measured by fasting plasma glucose and insulin. RESULTS: Fifty two participants completed the study (mean age: 12.0 +/- 2.0 y, 35 boys); both groups showed significantly decreased BMI z-score but similar changes in fat and fat-free mass. The low-GI group demonstrated a significant decline in fasting plasma insulin (22.2 +/- 14.3 to 13.7 +/- 10.9 mU/l; P = 0.004) and homeostatic model of assessment-insulin resistance (4.8 +/- 3.3 to 2.9 +/- 2.3; P = 0.007), whereas the control group did not. However, general linear model showed no significant difference in insulin resistance between groups after adjusting for baseline levels, suggesting that the greater reduction in insulin resistance in the low-GI group may be explained by higher baseline values. CONCLUSION: Despite subtle effects on body composition, a low-GI diet may improve insulin sensitivity in obese children with high baseline insulin. A bigger study in obese children with insulin resistance could be worthwhile to confirm our findings. PMID- 26270576 TI - Gestational and postnatal modulation of esophageal sphincter reflexes in human premature neonates. AB - BACKGROUND: Effects of gestational age (GA) and postnatal maturation on upper and lower esophageal sphincter (UES and LES) reflex development remain unclear. We hypothesized very-preterm (VPT) born neonates (< 32 wk GA) have delayed maturation of UES contractile reflex (UESCR) and LES relaxation reflex (LESRR) vs. preterm (PT) born (32-37 wk GA) neonates. METHODS: Using provocative manometry, effects of 1,263 graded mid-esophageal stimuli (air, liquid) on sensory-motor characteristics of UESCR and LESRR were investigated in 24 VPT-born and 12 PT-born neonates (37.8 +/- 0.6 vs. 38.9 +/- 0.4 wk postmenstrual age respectively, P = 0.14). RESULTS: In response to liquid stimuli (vs. air), VPT born neonates displayed prolonged UESCR and LESRR response latencies (P < 0.001) and prolonged UESCR and LESRR durations (P < 0.01); unlike PT-born neonates, who exhibit prolonged LESRR response latency (P < 0.01), but similar UESCR and LESRR durations (P = 0.2). Differences were noted in LESRR duration in VPT vs. PT neonates for air stimuli (P = 0.04). With liquid stimuli, increasing GA was associated with decreasing response onset latencies to UESCR and LESRR (P < 0.05), and increasing LESRR duration (P = 0.02). CONCLUSION: Using GA as categorical or continuous variable, vagus-mediated mechano-sensitive and liquid sensitive reflex characteristics of UESCR and LESRR are distinct; LESRR differs with varying intrauterine maturation suggesting inhibitory modulation progresses with advancing maturation. PMID- 26270577 TI - Assessment of long-term safety and efficacy of intranasal mesenchymal stem cell treatment for neonatal brain injury in the mouse. AB - BACKGROUND: For clinical translation, we assessed whether intranasal mesenchymal stem cell (MSC) treatment after hypoxia-ischemia (HI) induces neoplasia in the brain or periphery at 14 mo. Furthermore, the long-term effects of MSCs on behavior and lesion size were determined. METHOD: HI was induced in 9-d-old mice. Pups received an intranasal administration of 0.5 * 10(6) MSCs or vehicle at 10 d post-HI. Full macroscopical and microscopical pathological analysis of 39 organs per mouse was performed. Sensorimotor behavior was assessed in the cylinder rearing test at 10 d, 28 d, 6 mo, and 9 mo. Cognition was measured with the novel object recognition test at 3 and 14 mo post-HI. Lesion size was determined by analyzing mouse-anti-microtubule-associated protein 2 (MAP2) and mouse-anti myelin basic protein (MBP) staining at 5 wk and 14 mo. RESULTS: At 14 mo post-HI, we did not observe any neoplasia in the nasal turbinates, brain, or other organs of HI mice treated with MSCs. Furthermore, our results show that MSC-induced improvement of sensorimotor and cognitive function is long lasting. In contrast, HI-vehicle mice showed severe behavioral impairment. Recovery of MAP2- and MBP positive area lasted up to 14 mo following MSC treatment. CONCLUSION: Our results provide strong evidence of the long-term safety and positive effects of MSC treatment following neonatal HI in mice. PMID- 26270578 TI - Serum eotaxin-1 is increased in extremely-low-birth-weight infants with bronchopulmonary dysplasia or death. AB - BACKGROUND: Early systemic inflammation in extremely-low-birth-weight (ELBW) infants is associated with an increased risk of bronchopulmonary dysplasia (BPD). Our objective was to identify circulating biomarkers and develop prediction models for BPD/death soon after birth. METHODS: Blood samples from postnatal day 1 were analyzed for C-reactive protein (CRP) by enzyme-linked immunosorbent assay and for 39 cytokines/chemokines by a multiplex assay in 152 ELBW infants. The primary outcome was physiologic BPD or death by 36 wk. CRP, cytokines, and clinical variables available at <=24 h were used for forward stepwise regression and Classification and Regression Tree (CART) analysis to identify predictors of BPD/death. RESULTS: Overall, 24% developed BPD and 35% died or developed BPD. Regression analysis identified birth weight and eotaxin (CCL11) as the two most significant variables. CART identified FiO2 at 24 h (11% BPD/death if FiO2 <=28%, 49% if >28%) and eotaxin in infants with FiO2 > 28% (29% BPD/death if eotaxin was <=84 pg/ml; 65% if >84) as variables most associated with outcome. CONCLUSION: Eotaxin measured on the day of birth is useful for identifying ELBW infants at risk of BPD/death. Further investigation is required to determine if eotaxin is involved in lung injury and pathogenesis of BPD. PMID- 26270580 TI - Liquid scintillation counting methodology for (99)Tc analysis: a remedy for radiopharmaceutical waste. AB - This paper presents a new approach for liquid scintillation counting (LSC) analysis of single-radionuclide samples containing appreciable organic or inorganic quench. This work offers better analytical results than existing LSC methods for technetium-99 ((99g)Tc) analysis with significant savings in analysis cost and time. The method was developed to quantify (99g)Tc in environmental liquid and urine samples using LSC. Method efficiency was measured in the presence of 1.9 to 11 900 ppm total dissolved solids. The resultant quench curve proved to be effective for quantifying spiked (99g)Tc activity in deionized water, tap water, groundwater, seawater, and urine samples. Counting efficiency was found to be 91.66% for Ultima Gold LLT (ULG-LLT) and Ultima Gold (ULG). Relative error in spiked (99g)Tc samples was +/-3.98% in ULG and ULG-LLT cocktails. Minimum detectable activity was determined to be 25.3 and 22.7 mBq for ULG-LLT and ULG cocktails, respectively. A preconcentration factor of 1000 was achieved at 100 degrees C for 100% chemical recovery. PMID- 26270579 TI - Augmented cardiovascular responses to episodes of repetitive compared with isolated respiratory events in preschool children with sleep-disordered breathing. AB - BACKGROUND: Childhood sleep disordered breathing (SDB) presents as isolated respiratory events or episodes of consecutive repetitive events. We hypothesized that the surge in blood pressure (BP) and heart rate (HR) would be greater at the termination of events during episodes of repetitive events than following isolated events. METHODS: % change in HR and pulse transit time (PTT; inverse surrogate of BP) were calculated from the last half of an event to: (i) between successive repetitive events; (ii) termination of the last repetitive event; (iii) event termination for isolated events. RESULTS: 69% of the children exhibiting both isolated and repetitive events had more repetitive than isolated events. %HR change between repetitive events (27 +/- 1%) was greater than at event termination for isolated events (17 +/- 1%; P < 0.001). %PTT change at the termination of the last repetitive event (-8 +/- 2%) was greater than at the termination of isolated events (-2 +/- 2%; P < 0.05). CONCLUSION: Episodes of repetitive respiratory events evoke a greater acute cardiovascular response, including surges in BP and HR between events, than do isolated events. Given that the majority of respiratory events in preschool children occur as repetitive episodes, this finding should be taken into account when assessing the impact of respiratory events for a given child. PMID- 26270582 TI - Should we use gabapentin for postoperative pain control? PMID- 26270581 TI - Histamine H4 receptor activation alleviates neuropathic pain through differential regulation of ERK, JNK, and P38 MAPK phosphorylation. AB - Histamine plays a complex role in pain modulation with opposite roles in nociception for histamine receptor subtypes 1, 2, and 3. The histamine H4 receptor (H4R) is expressed primarily on cells involved in inflammation and immune responses with a proinflammatory activity, but little is known about the role in nociception of neuronal H4R. To investigate the effects of neuronal H4R in pain transmission, the effects produced by the H4R agonist ST-1006 were detected in the spared nerve injury model of neuropathic pain. ST-1006 counteracted mechanical allodynia in neuropathic mice, an effect prevented by the H4R antagonist JNJ 10191584. In spared nerve injury mice, an early over phosphorylation of ERK1 and ERK2 was observed in the dorsal root ganglia (DRG), spinal cord, and sciatic nerve. A progressive and long-lasting activation of JNK1 was observed in the sciatic nerve and, to a lesser extent, in the spinal cord and DRG. An increased p-P38 content was detected in the spinal cord and DRG, with no modification in the sciatic nerve. Administration of ST-1006 prevented phosphorylation of all 3 MAPK within DRG, and phosphorylation of ERK1, ERK2, and pJNK1 in the sciatic nerve. In the spinal cord, the H4R agonist prevented selectively the pERK2 increase with no effect on pJNK1 and p-P38 levels. Double immunofluorescence experiments showed a neuronal localization and site of action for H4R. These findings suggest a prevalent modulation of ERK activity after H4R stimulation and indicate the DRG as prominent site of action for H4R-mediated antineuropathic activity. Targeting neuronal H4R with selective agonists could have therapeutic potential for neuropathic pain treatment. PMID- 26270583 TI - Protein kinase C gamma-mediated phosphorylation of GluA1 in the postsynaptic density of spinal dorsal horn neurons accompanies neuropathic pain, and dephosphorylation by calcineurin is associated with prolonged analgesia. AB - Loss of calcineurin (protein phosphatase 3) activity and protein content in the postsynaptic density (PSD) of spinal dorsal horn neurons was associated with pain behavior after chronic constriction injury (CCI) of the rat sciatic nerve, and intrathecal administration of the phosphatase provided prolonged analgesia (Miletic et al. 2013). In this study, we examined whether one consequence of the loss of calcineurin was the persistent phosphorylation of the GluA1 subunit of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropioinic acid (AMPAR) receptors in the PSD. This would allow continual activation of AMPAR receptors at the synapse to help maintain a long-lasting enhancement of synaptic function, ie, neuropathic pain. We also investigated if the phosphorylation was mediated by protein kinase A (PKA), protein kinase C gamma (PKCgamma), or calcium-calmodulin dependent kinase II (CaMKII), and if the prolonged calcineurin analgesia was associated with GluA1 dephosphorylation. Mechanical thresholds and thermal latencies were obtained before CCI. Seven days later, the behavioral testing was repeated before saline, calcineurin, or the specific peptide inhibitors of PKA (PKI-tide), PKCgamma (PKC 19-31), or CaMKII (autocamtide-2-related inhibitory peptide) were injected intrathecally. The behavior was retested before the animals were euthanized and their PSD isolated. All CCI animals developed mechanical and thermal hypersensitivity. This was associated with phosphorylation of GluA1 in the ipsilateral PSD at Ser831 (but not Ser845) by PKCgamma and not by PKA or CaMKII. Intrathecal treatment with calcineurin provided prolonged analgesia, and this was accompanied by GluA1 dephosphorylation. Therapy with calcineurin may prove useful in the prolonged clinical management of well-established neuropathic pain. PMID- 26270584 TI - Learned control over spinal nociception reduces supraspinal nociception as quantified by late somatosensory evoked potentials. AB - We have recently shown that subjects can learn to use cognitive-emotional strategies to suppress their spinal nociceptive flexor reflex (RIII reflex) under visual RIII feedback and proposed that this reflects learned activation of descending pain inhibition. Here, we investigated whether learned RIII suppression also affects supraspinal nociception and whether previous relaxation training increases success. Subjects were trained over 3 sessions to reduce their RIII size by self-selected cognitive-emotional strategies. Two groups received true RIII feedback (with or without previous relaxation training) and a sham group received false feedback (15 subjects per group). RIII reflexes, late somatosensory evoked potentials (SEPs), and F-waves were recorded and pain intensity ratings collected. Both true feedback groups achieved significant (P < 0.01) but similar RIII suppression (to 79% +/- 21% and 70% +/- 17% of control). Somatosensory evoked potential amplitude (100-150 milliseconds after stimulation) was reduced in parallel with the RIII size (r = 0.57, P < 0.01). In the sham group, neither RIII size nor SEP amplitude was significantly reduced during feedback training. Pain intensity was significantly reduced in all 3 groups and also correlated with RIII reduction (r = 0.44, P < 0.01). F-wave parameters were not affected during RIII suppression. The present results show that learned RIII suppression also affects supraspinal nociception as quantified by SEPs, although effects on pain ratings were less clear. Lower motor neuron excitability as quantified by F-waves was not affected. Previous relaxation training did not significantly improve RIII feedback training success. PMID- 26270585 TI - Men, masculinity, and pain. PMID- 26270586 TI - Preoperative dexamethasone reduces acute but not sustained pain after lumbar disk surgery: a randomized, blinded, placebo-controlled trial. AB - Glucocorticoids have attracted increasing attention as adjuvants in the treatment of acute postoperative pain. Furthermore, anecdotal reports may support glucocorticoids for preventing sustained postoperative pain. We explored preoperative dexamethasone combined with paracetamol and ibuprofen on acute and sustained pain after lumbar disk surgery. In this blinded study, 160 patients undergoing lumbar disk surgery were randomly assigned to 16 mg IV dexamethasone or placebo. All patients received perioperative paracetamol and ibuprofen, and postoperative IV patient-controlled analgesia with morphine. Primary outcome was pain during mobilization (visual analog scale) 2 to 24 hours postoperatively. Secondary outcomes were acute pain at rest, morphine consumption, nausea, vomiting, ondansetron consumption, sedation, and quality of sleep. Patients were followed up by written questionnaire 3 months postoperatively. Acute pain during mobilization (weighted average area under the curve, 2-24 hours) was significantly reduced in the dexamethasone group: 33 (22) mm vs placebo 43 (18) mm, (95% confidence interval [CI] 3-16) P = 0.005. Vomiting 0 to 24 hours postoperatively was reduced in the dexamethasone group (17 episodes) vs placebo (51 episodes) P = 0.036. No other differences were observed. However, 6.5% (95% CI 2-15) in the dexamethasone group vs placebo 0% had an antibiotically treated wound infection (P = 0.13). Sixteen percent (95% CI 7-26) vs 8% (95% CI 0-17) reported new weakness/paralysis of the legs in the dexamethasone and placebo groups, respectively, 3 months postoperatively (P = 0.20). In conclusion, preoperative dexamethasone significantly reduced pain during mobilization and vomiting, after lumbar disk surgery. No significant effects were observed 3 months postoperatively. PMID- 26270587 TI - Inhibition of the primary sensorimotor cortex by topical anesthesia of the forearm in patients with complex regional pain syndrome. AB - Complex regional pain syndrome (CRPS) type I is characterized by somatosensory and motor deficits, and abnormalities have been reported for primary somatosensory (S1) and motor cortex (M1) excitability. For the latter, reduced short-latency intracortical inhibition (SICI) has been demonstrated in the somatotopic representation of the affected side. Recently, an intervention of applying anesthetic cream to the forearm has been shown to modulate both somatosensory deficits (eg, spatial tactile resolution [STR]) and SICI measured in hand muscles. We examined the efficacy of this intervention in patients with CRPS I. Cutaneous anesthesia of the forearm of the affected side was used to increase SICI of hand muscles and decrease impaired STR of the affected limb. In a double-blinded placebo-controlled study, we enrolled 12 patients with unilateral CRPS I of the hand in the chronic state. Before and after intervention, we measured motor evoked potentials of the first dorsal interosseus to obtain SICI and STR of both hand sides. Patients showed decreased STR on the tip of the thumb of their affected side, which improved after anesthetic cream but not after placebo application. Hand motor function of the affected side improved after anesthetic cream but not after placebo. Pain intensity was not modulated after intervention. At both hemispheres, SICI was decreased compared with reference values but selectively increased at the intervention side only after analgesic cream and not after placebo. Temporary deafferentation of an area neighbouring the CRPS-affected region can modulate neuropathological characteristics of CRPS and might be a promising strategy for therapeutic interventions. PMID- 26270588 TI - Involvement of peripheral artemin signaling in tongue pain: possible mechanism in burning mouth syndrome. AB - Burning mouth syndrome is characterized by altered sensory qualities, namely tongue pain hypersensitivity. We found that the mRNA expression of Artemin (Artn) in the tongue mucosa of patients with burning mouth syndrome was significantly higher than that of control subjects, and we developed a mouse model of burning mouth syndrome by application of 2,4,6-trinitrobenzene sulfonic acid (TNBS) diluted with 50% ethanol to the dorsum of the tongue. TNBS treatment to the tongue induced persistent, week-long, noninflammatory tongue pain and a significant increase in Artn expression in the tongue mucosa and marked tongue heat hyperalgesia. Following TNBS treatment, the successive administration of the transient receptor potential vanilloid 1 (TRPV1) antagonist SB366791 or neutralizing anti-Artn antibody completely inhibited the heat hyperalgesia. The number of glial cell line-derived neurotrophic factor family receptor alpha3 (GFRalpha3)-positive and TRPV1-positive trigeminal ganglion (TG) neurons innervating the tongue significantly increased following TNBS treatment and was significantly reduced by successive administration of neutralizing anti-Artn antibody. The capsaicin-induced current in TG neurons innervating the tongue was enhanced following TNBS treatment and was inhibited by local administration of neutralizing anti-Artn antibody to the tongue. These results suggest that the overexpression of Artn in the TNBS-treated tongue increases the membrane excitability of TG neurons innervating the tongue by increasing TRPV1 sensitivity, which causes heat hyperalgesia. This model may be useful for the study of tongue pain hypersensitivity associated with burning mouth syndrome. PMID- 26270589 TI - The influence of offset analgesia on the onset and offset of pain in patients with fibromyalgia. AB - Offset analgesia (OA) is a form of endogenous pain inhibition characterized by a disproportionately large reduction in pain perception after a small decrease in temperature during noxious thermal stimulation. In this study, the presence of OA was evaluated in patients with fibromyalgia and compared with healthy age-matched and sex-matched controls. Offset analgesia was induced by noxious thermal stimulation on the arm, causing a visual analog score (VAS) of about 50 mm, followed by a 1 degrees C temperature decrease. The OA response is defined by the reduction in VAS induced by the 1 degrees C stimulus decrease. To assess whether the OA response could be enhanced, 2 tests were applied: repetition of the OA paradigm and 1 degrees C temperature downward steps after an initial OA test (downward step test). To assess whether OA affects onset of pain, OA steps at increasing temperatures (upward OA step test) were applied. Patients with fibromyalgia had reduced OA responses with a reduction in VAS of 65.3 +/- 4.5% (mean +/- SD) vs controls 97.8 +/- 4.6% (P < 0.001). Decreased OA responses were not enhanced or restored by repeating the OA paradigm or by the downward step test. Defective engagement of OA had a significant effect on pain onset, as observed from the upward OA step test, with less tolerability to noxious pain stimulation in patients with fibromyalgia. In conclusion, patients with fibromyalgia showed less pain inhibition as measured by the OA paradigm, which influenced both the onset and offset of pain. PMID- 26270590 TI - Striatal-enriched protein tyrosine phosphatase modulates nociception: evidence from genetic deletion and pharmacological inhibition. AB - The information from nociceptors is processed in the dorsal horn of the spinal cord by complex circuits involving excitatory and inhibitory interneurons. It is well documented that GluN2B and ERK1/2 phosphorylation contributes to central sensitization. Striatal-enriched protein tyrosine phosphatase (STEP) dephosphorylates GluN2B and ERK1/2, promoting internalization of GluN2B and inactivation of ERK1/2. The activity of STEP was modulated by genetic (STEP knockout mice) and pharmacological (recently synthesized STEP inhibitor, TC-2153) approaches. STEP(61) protein levels in the lumbar spinal cord were determined in male and female mice of different ages. Inflammatory pain was induced by complete Freund's adjuvant injection. Behavioral tests, immunoblotting, and electrophysiology were used to analyze the effect of STEP on nociception. Our results show that both genetic deletion and pharmacological inhibition of STEP induced thermal hyperalgesia and mechanical allodynia, which were accompanied by increased pGluN2B(Tyr1472) and pERK1/2(Thr202/Tyr204)levels in the lumbar spinal cord. Striatal-enriched protein tyrosine phosphatase heterozygous and knockout mice presented a similar phenotype. Furthermore, electrophysiological experiments showed that TC-2153 increased C fiber-evoked spinal field potentials. Interestingly, we found that STEP(61) protein levels in the lumbar spinal cord inversely correlated with thermal hyperalgesia associated with age and female gender in mice. Consistently, STEP knockout mice failed to show age-related thermal hyperalgesia, although gender-related differences were preserved. Moreover, in a model of inflammatory pain, hyperalgesia was associated with increased phosphorylation-mediated STEP(61) inactivation and increased pGluN2B(Tyr1472) and pERK1/2(Thr202/Tyr204)levels in the lumbar spinal cord. Collectively, the present results underscore an important role of spinal STEP activity in the modulation of nociception. PMID- 26270591 TI - A systematic review and meta-analysis of the prevalence of chronic widespread pain in the general population. AB - Chronic widespread pain (CWP) is common and associated with poor general health. There has been no attempt to derive a robust prevalence estimate of CWP or assess how this is influenced by sociodemographic factors. This study therefore aimed to determine, through a systematic review and meta-analysis, the prevalence of CWP in the adult general population and explore variation in prevalence by age, sex, geographical location, and criteria used to define CWP. MEDLINE, Embase, CINAHL, and AMED were searched using a search strategy combining key words and related database-specific subject terms to identify relevant cohort or cross-sectional studies published since 1990. Included articles were assessed for risk of bias. Prevalence figures for CWP (American College of Rheumatology criteria) were stratified according to geographical location, age, and sex. Potential sources of variation were investigated using subgroup analyses and meta-regression. Twenty five articles met the eligibility criteria. Estimates for CWP prevalence ranged from 0% to 24%, with most estimates between 10% and 15%. The random-effects pooled prevalence was 10.6% (95% confidence intervals: 8.6-12.9). When only studies at low risk of bias were considered pooled, prevalence increased to 11.8% (95% confidence intervals: 10.3-13.3), with reduced but still high heterogeneity. Prevalence was higher in women and in those aged more than 40 years. There was some limited evidence of geographic variation and cultural differences. One in 10 adults in the general population report chronic widespread pain with possible sociocultural variation. The possibility of cultural differences in pain reporting should be considered in future research and the clinical assessment of painful conditions. PMID- 26270593 TI - Aspirin response: Differences in serum thromboxane B2 levels between clinical studies. AB - Serum thromboxane B2 (TxB2) is a specific marker of platelet inhibition by aspirin. Yet, TxB2 levels differ by up to 10-fold between some aspirin-treated patient cohorts. This study aimed to identify factors responsible for differences in serum TxB2 between cohorts in the ADRIE study (n = 657) and the BOSTON study (n = 678) of aspirin-treated cardiovascular patients originally tested with different ELISA assays. TxB2 levels were assessed in representative subgroups of the two cohorts (34 samples in BOSTON and 39 in ADRIE) by both ELISAs, as well as liquid chromatography and tandem mass spectroscopy (MS). A multivariate analysis was performed on the whole cohort database to identify determinants of the difference of TxB2 levels between cohorts. There was no systematic bias between the original ELISA TxB2 values and the MS values and the median difference was small, 0.12 ng/ml, thus not explaining the difference between median TxB2 levels in the two study populations (7 and 0.6 ng/ml in the ADRIE and BOSTON studies, respectively). In the combined dataset of the ADRIE and BOSTON cohorts (n = 1342), body mass index, age, gender, aspirin dose, time from aspirin intake to blood draw, NSAID intake, platelet count and C-reactive protein were significantly associated with TxB2 levels. After adjustment for patient characteristics, the difference between cohorts did not decrease. Unexplained differences in serum TxB2 levels in different populations of aspirin-treated cardiovascular patients suggest that further studies are needed to confirm the role of serum TxB2 level as a prognostic factor or rather as a marker of therapeutic observance. PMID- 26270595 TI - A Scanning Electron Microscopic Study of Enamel Surfaces of Incipient Caries. AB - The surface changes of natural incipient caries in human teeth were examined by scanning electron microscopy. Numerous small round depressions due to dissolved prism ends are observed. The prism sheaths seem to be preferentially demineralized, followed by demineralization of prism cores. Perikymata are well pronounced. Focal holes and relatively large dissolution areas can be present. A new prismatic pattern of destruction with an appearance of fish scales is found. Evidence of remineralization of the incipient carious lesions is seen on the surfaces of the lesions. This study disagrees with the concept of an intact enamel surface layer. PMID- 26270594 TI - Effects of penicillin and erythromycin on adherence of invasive and noninvasive isolates of Streptococcus pyogenes to laminin. AB - This study investigated the possible relationship between the invasiveness of group A Streptococcus (GAS) strains and their abilities to adhere to laminin and assessed the effects of subinhibitory concentrations of penicillin and erythromycin on the ability of GAS to adhere to laminin. The adherence of noninvasive and highly invasive isolates of GAS to laminin was significantly higher than the adherence displayed by isolates of low invasiveness. Antibiotic treatment caused significant reductions in adherence to laminin in all three groups of strains. Penicillin was more successful in reducing the adherence abilities of the tested GAS strains than erythromycin. PMID- 26270592 TI - Was it a pain or a sound? Across-species variability in sensory sensitivity. AB - Natural selection has shaped the physiological properties of sensory systems across species, yielding large variations in their sensitivity. Here, we used laser stimulation of skin nociceptors, a widely used technique to investigate pain in rats and humans, to provide a vivid example of how ignoring these variations can lead to serious misconceptions in sensory neuroscience. In 6 experiments, we characterized and compared the physiological properties of the electrocortical responses elicited by laser stimulation in rats and humans. We recorded the electroencephalogram from the surface of the brain in freely moving rats and from the scalp in healthy humans. Laser stimuli elicited 2 temporally distinct responses, traditionally interpreted as reflecting the concomitant activation of different populations of nociceptors with different conduction velocities: small-myelinated Adelta-fibres and unmyelinated C-fibres. Our results show that this interpretation is valid in humans, but not in rats. Indeed, the early response recorded in rats does not reflect the activation of the somatosensory system, but of the auditory system by laser-generated ultrasounds. These results have wide implications: retrospectively, as they prompt for a reconsideration of a large number of previous interpretations of electrocortical rat recordings in basic, preclinical, and pharmacological research, and prospectively, as they will allow recording truly pain-related cortical responses in rats. PMID- 26270596 TI - Reactivity of Hydride Bridges in High-Spin [3M-3(MU-H)] Clusters (M = FeII, CoII). AB - The designed [3M-3(MU-H)] clusters (M = Fe(II), Co(II)) Fe3H3L (1-H) and Co3H3L (2-H) [where L(3-) is a tris(beta-diketiminate) cyclophane] were synthesized by treating the corresponding M3Br3L complexes with KBEt3H. From single-crystal X ray analysis, the hydride ligands are sterically protected by the cyclophane ligand, and these complexes selectively react with CO2 over other unsaturated substrates (e.g., CS2, Me3SiCCH, C2H2, and CH3CN). The reaction of 1-H or 2-H with CO2 at room temperature yielded Fe3(OCHO)(H)2L (1-CO2) or Co3(OCHO)(H)2L (2 CO2), respectively, which evidence the differential reactivity of the hydride ligands within these complexes. The analogous reactions at elevated temperatures revealed a distinct difference in the reactivity pattern for 2-H as compared to 1 H; Fe3(OCHO)3L (1-3CO2) was generated from 1-H, while 2-H afforded only 2-CO2. PMID- 26270601 TI - A modified approach for performing ultrasound-guided radial, ulnar, median and musculocutaneous nerve block in a dog. PMID- 26270597 TI - Validity and Reliability of the US National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO CTCAE). AB - IMPORTANCE: To integrate the patient perspective into adverse event reporting, the National Cancer Institute developed a patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). OBJECTIVE: To assess the construct validity, test-retest reliability, and responsiveness of PRO CTCAE items. DESIGN, SETTING, AND PARTICIPANTS: A total of 975 adults with cancer undergoing outpatient chemotherapy and/or radiation therapy enrolled in this questionnaire-based study between January 2011 and February 2012. Eligible participants could read English and had no clinically significant cognitive impairment. They completed PRO-CTCAE items on tablet computers in clinic waiting rooms at 9 US cancer centers and community oncology practices at 2 visits 1 to 6 weeks apart. A subset completed PRO-CTCAE items during an additional visit 1 business day after the first visit. MAIN OUTCOMES AND MEASURES: Primary comparators were clinician-reported Eastern Cooperative Oncology Group Performance Status (ECOG PS) and the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30). RESULTS: A total of 940 of 975 (96.4%) and 852 of 940 (90.6%) participants completed PRO CTCAE items at visits 1 and 2, respectively. At least 1 symptom was reported by 938 of 940 (99.8%) participants. Participants' median age was 59 years; 57.3% were female, 32.4% had a high school education or less, and 17.1% had an ECOG PS of 2 to 4. All PRO-CTCAE items had at least 1 correlation in the expected direction with a QLQ-C30 scale (111 of 124, P<.05 for all). Stronger correlations were seen between PRO-CTCAE items and conceptually related QLQ-C30 domains. Scores for 94 of 124 PRO-CTCAE items were higher in the ECOG PS 2 to 4 vs 0 to 1 group (58 of 124, P<.05 for all). Overall, 119 of 124 items met at least 1 construct validity criterion. Test-retest reliability was 0.7 or greater for 36 of 49 prespecified items (median [range] intraclass correlation coefficient, 0.76 [0.53-.96]). Correlations between PRO-CTCAE item changes and corresponding QLQ C30 scale changes were statistically significant for 27 prespecified items (median [range] r=0.43 [0.10-.56]; all P<=.006). CONCLUSIONS AND RELEVANCE: Evidence demonstrates favorable validity, reliability, and responsiveness of PRO CTCAE in a large, heterogeneous US sample of patients undergoing cancer treatment. Studies evaluating other measurement properties of PRO-CTCAE are under way to inform further development of PRO-CTCAE and its inclusion in cancer trials. PMID- 26270604 TI - Application of Fluorescence Spectroscopy to Forensic Science. AB - Over the last decade, both ultraviolet and infrared fluorescence techniques have been applied to a number of areas of forensic science. Much of this work has been spurred on by the development of laser methods of visualization. One of the major beneficiaries of this attention to lasers and fluorescence has been in fingerprints. A great deal of research has been done on the development of new fluorescent dyes for visualizing fingerprints with a laser. Fluorescence has also been applied extensively to questioned-document analysis, principally in characterization of inks. Other types of evidence that use fluorimetric analysis include drugs, glass, petroleum products, and biological samples. This article will discuss these applications to forensic science and their advantages relative to other methods of analysis. PMID- 26270599 TI - Down-titration of Adalimumab and Etanercept in Psoriatic Patients: A Multicentre Observational Study. PMID- 26270605 TI - Measuring Alcohol in Blood and Breath for Forensic Purposes - A Historical Review. AB - This review concerns important events and trends in the evolution of chemical tests for alcohol intoxication on two continents; Europe and North America. In particular, the pioneer workers in this field and their major contributions to forensic alcohol analysis are emphasized. Quantitative methods for the determination of alcohol in blood, breath, and urine appeared early in the twentieth century and experimental alcohol research had already started in several European countries. The first statutory limits of blood-alcohol concentration (BAC) were introduced in Norway and Sweden during the 1930-1940s where Widmark's micro-diffusion method was approved for forensic purposes. Between 1931-1935 in the U.S., the first instrument (the Drunkometer) was developed for measuring the concentration of alcohol in a person's breath to supplement various clinical signs and symptoms of drunkenness. The breath-alcohol concentration (BrAC) was always translated into the presumed coexisting BAC to furnish corroborative or presumptive evidence of impairment at the wheel. After the Breathalyzer device was developed by Borkenstein around 1953-54, breath alcohol testing became firmly established for law enforcement purposes in the U.S. and Canada. The classic wet-chemistry methods of blood-alcohol analysis were displaced by enzymatic procedures in the early 1950s and in the 1960s gas chromatographic (GC) methods dominated. Today, headspace GC is the mainstay in forensic science laboratories for the determination of alcohol and other volatile substances in body fluids. The first breath-alcohol devices used in Europe were relatively simple screening tests for alcohol at the roadside and positive results were always followed-up by quantitative analysis of alcohol in blood or urine. The technology of breath-alcohol testing has changed dramatically over the years from chemical oxidation and colorimetric procedures towards physicochemical techniques such as gas chromatography, electrochemical oxidation, and multiple wavelength infrared spectrophotometry. In the early 1980s evidential breath alcohol instruments were approved for law enforcement purposes in many European countries and threshold limits of BrAC were introduced alongside the existing statutory BAC limits. PMID- 26270598 TI - Synthesis of Peptides Containing C-Terminal Esters Using Trityl Side-Chain Anchoring: Applications to the Synthesis of C-Terminal Ester Analogs of the Saccharomyces cerevisiae Mating Pheromone a-Factor. AB - Peptides containing C-terminal esters are an important class of bioactive molecules that includes a-factor, a farnesylated dodecapeptide, involved in the mating of Saccharomyces cerevisiae. Here, results that expand the scope of solid phase peptide synthetic methodology that uses trityl side-chain anchoring for the preparation of peptides with C-terminal cysteine alkyl esters are described. In this method, Fmoc-protected C-terminal cysteine esters are anchored to trityl chloride resin and extended by standard solid-phase procedures followed by acidolytic cleavage and HPLC purification. Analysis using a Gly-Phe-Cys-OMe model tripeptide revealed minimal epimerization of the C-terminal cysteine residue under basic conditions used for Fmoc deprotection. (1)H NMR analysis of the unfarnesylated a-factor precursor peptide confirmed the absence of epimerization. The side-chain anchoring method was used to produce wild-type a-factor that contains a C-terminal methyl ester along with ethyl-, isopropyl-, and benzyl ester analogs in good yield. Activity assays using a yeast-mating assay demonstrate that while the ethyl and isopropyl esters manifest near-wild-type activity, the benzyl ester-containing analog is ca. 100-fold less active. This simple method opens the door to the synthesis of a variety of C-terminal ester modified peptides that should be useful in studies of protein prenylation and other structurally related biological processes. PMID- 26270602 TI - Ortho-7 bound to the active-site gorge of free and OP-conjugated acetylcholinesterase: cation-pi interactions. AB - Despite the immense importance of cation-pi interactions prevailing in bispyridinium drug acetylcholinesterase (AChE) complexes, a precise description of cation-pi interactions at molecular level has remained elusive. Here, we consider a bispyridinium drug, namely, ortho-7 in three different structures of AChE, with and without complexation with organophosphorus (OP) compounds for detailed investigation using all atom molecular dynamics simulation. By quantum mechanical calculations, Y72, W86, Y124, W286, Y337, and Y341 aromatic residues of the enzyme are investigated for possible cation-pi interactions with ortho-7. The cation-pi interactions in each of the protein-drug complexes are studied using distance, angle, a suitable functional form of them, and electrostatic criteria. The variation of cation-pi functional is remarkably consistent with that of the Columbic variation. It is clearly observed that cation-pi interactions for some of the residues in the catalytic active site (CAS) and peripheral anionic site (PAS) of the enzyme are either enhanced or reduced based on the nature of OP conjugation (i.e., nerve gas, tabun or pesticide, fenamiphos) when compared with the OP-free enzyme. The strength of cation-pi interaction is strongly dependent on the type OP conjugation. The effect of conjugation at CAS is also seen to influence the cation-pi interaction at the PAS region. The variation of cation-pi interactions on the type of conjugating OP compounds might be suggestive of a reason as to why wide spectrum drug against any OP poisoning is yet to arrive in the market. PMID- 26270606 TI - Modern Approaches for the Examination of Toolmarks and Other Surface Marks. AB - Numerous techniques have been developed over the years in the examination of toolmarks and footwear impression. Recent development in the following aspects are described: shoemark enhancement techniques, new casting materials, comparison scanning electron microscopy, computerized identification of striations, and recovery of erased numbers in new metallic and polymeric materials. Furthermore, quality assurances and the duties of toolmark examiners are examine. PMID- 26270607 TI - Application of Bacillus subtilis to the roots of leafy greens, in the presence of Listeria innocua and Salmonella Newport, induces closure of stomata. AB - Plant growth-promoting rhizobacterium Bacillus subtilis UD1022 has been shown to trigger an induced systemic response in Arabidopsis thaliana. This interaction causes plant stomata to close, protecting the plant from infection by plant pathogens and thereby increasing crop yield. The purpose of this study was to determine whether UD1022 applied to the roots of plants is able to induce stomata closure in leafy greens as well as influence the persistence of human pathogens (Listeria and Salmonella) on plants. UD1022 induced stomata closure in the presence of human pathogens on both lettuce and spinach 3 h post-inoculation (p<0.0001). Results were confirmed by root inoculation with heat-killed UD1022, which did not induce stomata closure. Presence of UD1022 on lettuce roots significantly reduced the persistence of Listeria on plants after 3 days post inoculation (p=0.02) but had less of an effect on the persistence of Salmonella. The results of this study indicate that plant growth-promoting rhizobacterium B. subtilis UD1022 may be able to prevent contamination by some human pathogens. This is the first study to investigate the use of plant growth-promoting rhizobacteria to control the persistence of human pathogens on plants. PMID- 26270608 TI - Pediatric Home Sleep Apnea Testing: Slowly Getting There! AB - Pediatric OSA can result in significant neurocognitive, behavioral, cardiovascular, and metabolic morbidities. Prompt diagnosis and treatment are, therefore, of paramount importance. The current gold standard for diagnosis of OSA in children is in-laboratory polysomnography (PSG). Home sleep apnea testing has been considered as an alternative as it is potentially more cost effective, convenient, and accessible. This review concentrates mainly on the use of type 2 and 3 portable monitoring devices. The current evidence on the feasibility and diagnostic accuracy of home testing in the diagnosis of pediatric OSA was examined. Overall, the evidence in children is limited. Feasibility studies that have been performed have on the whole shown good results, with several reporting > 90% of their home recordings as meeting predetermined quality criteria regarding signal artifact and minimum recording time. The limited data comparing type 2 studies with in-laboratory PSG have shown no significant differences in respiratory parameters. The results pertaining to diagnostic accuracy of type 3 home sleep apnea testing devices are conflicting. Although more research is needed, home testing with at least a type 3 portable monitor offers a viable alternative in the diagnosis of otherwise healthy children with moderate to severe OSA, particularly in settings where access to polysomnography is scarce or unavailable. Of note, since most studies have been performed in habitually snoring healthy children, home sleep apnea testing may not be applicable to children with other comorbid conditions. In particular, CO2 monitoring is important in children in whom there is concern regarding nocturnal hypoventilation, such as children with neuromuscular disease, underlying lung disease, or obesity hypoventilation, and most home testing devices do not include a transcutaneous or end-tidal CO2 channel. PMID- 26270610 TI - Infant Mortality Statistics From the 2013 Period Linked Birth/Infant Death Data Set. AB - OBJECTIVES: This report presents 2013 period infant mortality statistics from the linked birth/infant death data set (linked file) by maternal and infant characteristics. The linked file differs from the mortality file, which is based entirely on death certificate data. METHODS: Descriptive tabulations of data are presented and interpreted. RESULTS: The U.S. infant mortality rate was 5.96 infant deaths per 1,000 live births in 2013, similar to the rate of 5.98 in 2012. The number of infant deaths was 23,446 in 2013, a decline of 208 infant deaths from 2012. From 2012 to 2013, infant mortality rates were stable for most race and Hispanic origin groups; declines were reported for two Hispanic subgroups: Cuban and Puerto Rican. Since 2005, the most recent high, the U.S. infant mortality rate has declined 13% (from 6.86), with declines in both neonatal and postneonatal mortality overall and for most groups. In 2013, infants born at 37 38 weeks of gestation (early term) had mortality rates that were 63% higher than for full-term (39-40 week) infants. For multiple births, the infant mortality rate was 25.84, 5 times the rate of 5.25 for singleton births. In 2013, 36% of infant deaths were due to preterm-related causes of death, and an additional 15% were due to causes grouped into the sudden unexpected infant death category. PMID- 26270609 TI - Conformations, hydrodynamic interactions, and instabilities of sedimenting semiflexible filaments. AB - The conformations and dynamics of semiflexible filaments subject to a homogeneous external (gravitational) field, e.g., in a centrifuge, are studied numerically and analytically. The competition between hydrodynamic drag and bending elasticity generates new shapes and dynamical features. We show that the shape of a semiflexible filament undergoes instabilities as the external field increases. We identify two transitions that correspond to the excitation of higher bending modes. In particular, for strong fields the filament stabilizes in a non-planar shape, resulting in a sideways drift or in helical trajectories. For two interacting filaments, we find the same transitions, with the important consequence that the new non-planar shapes have an effective hydrodynamic repulsion, in contrast to the planar shapes which attract themselves even when their osculating planes are rotated with respect to each other. For the case of planar filaments, we show analytically and numerically that the relative velocity is not necessarily due to a different drag of the individual filaments, but to the hydrodynamic interactions induced by their shape asymmetry. PMID- 26270611 TI - Image Analysis of Foods. AB - The structure of foods, both natural and processed ones, is controlled by many variables ranging from biology to chemistry and mechanical forces. The structure also controls many of the properties of the food, including consumer acceptance, taste, mouthfeel, appearance, and so on, and nutrition. Imaging provides an important tool for measuring the structure of foods. This includes 2-dimensional (2D) images of surfaces and sections, for example, viewed in a microscope, as well as 3-dimensional (3D) images of internal structure as may be produced by confocal microscopy, or computed tomography and magnetic resonance imaging. The use of images also guides robotics for harvesting and sorting. Processing of images may be needed to calibrate colors, reduce noise, enhance detail, and delineate structure and dimensions. Measurement of structural information such as volume fraction and internal surface areas, as well as the analysis of object size, location, and shape in both 2- and 3-dimensional images is illustrated and described, with primary references and examples from a wide range of applications. PMID- 26270612 TI - Combining Crystallography and Hydrogen-Deuterium Exchange to Study Galectin Ligand Complexes. AB - The physiological significance arising from translating information stored in glycans into cellular effects explains the interest in structurally defining lectin-carbohydrate recognition. The relatively small set of adhesion/growth regulatory galectins in chicken makes this system attractive to study the origins of specificity and divergence. Cell binding by using glycosylation mutants reveals binding of the N-terminal domain of chicken galectin-8 (CG-8N) to alpha 2,3-sialylated and galactose-terminated glycan chains. Cocrystals with lactose and its 3'-sialylated derivative disclose Arg58 as a key contact for the carboxylic acid and differences in loop lengths to the three homodimeric chicken galectins. Monitoring hydrogen-deuterium exchange by mass spectrometry revealed an effective reduction of deuteration after ligand binding within the contact area. In addition, evidence for changes in solvent accessibility of amide protons beyond this site was obtained. Their detection, which highlights the sensor capacity of this technique, encourages systematic studies on galectins and beyond. PMID- 26270613 TI - Estimation of organ doses to patients undergoing hepatic chemoembolization procedures. AB - The aim of this study is to evaluate organ and tissue absorbed doses to patients undergoing hepatic chemoembolization procedures performed in two hospitals in the city of Recife, Brazil. Forty eight patients undergoing fifty hepatic chemoembolization procedures were investigated. For the 20 cases with PA projection only, organs and tissues dose to KAP conversion coefficients were calculated using the mesh-based anthropometric phantom series FASH and MASH coupled to the EGSnrc Monte Carlo code. Clinical, dosimetric and irradiations parameters were registered for all patients. The maximum organ absorbed doses found were 2.4 Gy, 0.85 Gy, 0.76 Gy and 0.44 Gy for skin, kidneys, adrenals and liver, respectively. PMID- 26270614 TI - Professor Irena Hausmanowa-Petrusewicz, 1917-2015. PMID- 26270620 TI - Prolonged antibiotics for non-cystic fibrosis bronchiectasis in children and adults. AB - BACKGROUND: The vicious cycle hypothesis for bronchiectasis predicts that bacterial colonisation of the respiratory tract perpetuates inflammatory change. This damages the mucociliary escalator, preventing bacterial clearance and allowing persistence of pro-inflammatory mediators. Conventional treatment with physiotherapy and intermittent antibiotics is believed to improve the condition of people with bronchiectasis, although no conclusive data show that these interventions influence the natural history of the condition. Various strategies have been tried to interrupt this cycle of infection and inflammation, including prolonging antibiotic treatment with the goal of allowing the airway mucosa to heal. OBJECTIVES: To determine the benefits of prolonged antibiotic therapy in the treatment of patients with bronchiectasis. SEARCH METHODS: We searched the Cochrane Airways Group Trials Register and reference lists of identified articles. Searches were current as of February 2014. SELECTION CRITERIA: Randomised trials examining the use of prolonged antibiotic therapy (for four or more weeks) in the treatment of bronchiectasis compared with placebo or usual care. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We contacted study authors to ask for missing information. MAIN RESULTS: Eighteen trials met the inclusion criteria, randomly assigning a total of 1157 participants. Antibiotics were given for between four weeks and 83 weeks. Limited meta-analysis was possible because of the diversity of outcomes reported in these trials. Based on the number of participants with at least one exacerbation, the meta-analysis showed significant effects in favour of the intervention (odds ratio (OR) 0.31, 95% confidence interval (CI) 0.19 to 0.52; P value < 0.00001), with events occurring in 271 per 1000 people in the intervention arm (95% CI 126 to 385) and in 546 per 1000 in the control population, based on evidence of moderate quality. A non-statistically significant reduction in hospitalisation favoured the use of prolonged antibiotics with a moderate quality grade of supporting evidence (37 per 1000 in the intervention arm (95% CI 13 to 96) and 87 per 1000 in control (OR 0.40, 95% CI 0.14 to 1.11; P value = 0.08). Drug resistance developed in 36 of 220 participants taking antibiotics compared with 10 of 211 participants given placebo or standard therapy (OR 3.48, 95% CI 1.20 to 10.07; P value = 0.02), translating to natural frequencies of 155 per 1000 in the intervention arm (95% CI 59 to 346) and 50 per 1000 in the control arm. The intervention was well tolerated with no overall significant difference in withdrawal between treatment and placebo groups (OR 0.91, 95% CI 0.56 to 1.49). Diarrhoea was commonly reported as an adverse event, particularly with an oral intervention. AUTHORS' CONCLUSIONS: Available evidence shows benefit associated with use of prolonged antibiotics in the treatment of patients with bronchiectasis, at least halving the odds of exacerbation (with 275 fewer exacerbations per every 1000 people treated in the antibiotic arm compared with the control arm) and hospitalisation (50 fewer hospitalisations per 1000 people in the antibiotic arm compared with the control arm). However, the risk of emerging drug resistance is increased more than threefold. This review is limited by diversity of trials and by evidence of moderate to low quality. Further randomised controlled trials with adequate power and standardised end points are required. PMID- 26270622 TI - From the Ternary Eu(Au/In)2 and EuAu4(Au/In)2 with Remarkable Au/In Distributions to a New Structure Type: The Gold-Rich Eu5Au16(Au/In)6 Structure. AB - The ternary Eu(Au/In)2 (EuAu(0.46)In(1.54(2))) (I), EuAu4(Au/In)2 (EuAu(4+x)In(2 x) with x = 0.75(2) (II), 0.93(2), and 1.03(2)), and Eu5Au16(Au/In)6 (Eu5Au(17.29)In(4.71(3))) (III) have been synthesized, and their structures were characterized by single-crystal X-ray diffraction. I and II crystallize with the CeCu2-type (Pearson Symbol oI12; Imma; Z = 4; a = 4.9018(4) A; b = 7.8237(5) A; c = 8.4457(5) A) and the YbAl4Mo2-type (tI14; I4/mmm; Z = 2; a = 7.1612(7) A; c = 5.5268(7) A) and exhibit significant Au/In disorder. I is composed of an Au/In mixed diamond-related host lattice encapsulating Eu atoms, while the structure of II features ribbons of distorted, squared Au8 prisms enclosing Eu, Au, and In atoms. Combination of these structural motifs leads to a new structure type as observed for Eu5Au16(Au/In)6 (Eu5Au(17.29)In(4.71(3))) (oS108; Cmcm; Z = 4; a = 7.2283(4) A; b = 9.0499(6) A; c = 34.619(2) A), which formally represents a one dimensional intergrowth of the series EuAu2-"EuAu4In2". The site preferences of the disordered Au/In positions in II were investigated for different hypothetical "EuAu4(Au/In)2" models using the projector-augmented wave method and indicate that these structures attempt to optimize the frequencies of the heteroatomic Au In contacts. A chemical bonding analysis on two "EuAu5In" and "EuAu4In2" models employed the TB-LMTO-ASA method and reveals that the subtle interplay between the local atomic environments and the bond energies determines the structural and site preferences for these systems. PMID- 26270621 TI - Near-Infrared Light Manipulated Chemoselective Reductions Enabled by an Upconversional Supersandwich Nanostructure. AB - Core-satellite is one of the most powerful superstructures since it leads to enhanced or completely new properties through compatible combination of each component. Here we create a novel ceria-based core-shell-satellite supersandwich structure with near-infrared (NIR) light manipulated catalytic activity by integrating the upconversion luminescent and catalytic functionality of CeO2 nanoparticles. Specifically, lanthanide-doped octahedral CeO2 nanoparticles (o CeO2) are coated with silica layer (o-CeO2@SiO2) to enhance their luminescence intensity. The pH-dependent catalytic active cubic CeO2 nanoparticles (c-CeO2) are then assembled on the surface of o-CeO2@SiO2 to form the supersandwich structure (o-CeO2@SiO2@c-CeO2) following a classic chemical reaction. The upconversion quantum yield of o-CeO2 in this nanostructure can be nearly doubled. Furthermore, under NIR light irradiation, the o-CeO2@SiO2@c-CeO2 supersandwich structure based composite catalyst displays superior catalytic activity in selective reduction of aromatic nitro compounds to corresponding azo compounds, and the composite photocatalyst can be easily recycled for several times without significant loss of catalytic activity. This strategy may serve as a universal method for the construction of multifunctional nanostructures and shed light on the green chemistry for chemical synthesis. PMID- 26270624 TI - Visante Anterior Segment Optical Coherence Tomography Analysis of Morphologic Changes in the Anterior Segment Structures after Deep Sclerotomy Versus Phaco Deep Sclerotomy with Intraoperative Mitomycin-C and No Implant Use. AB - This article has been retracted. PMID- 26270623 TI - pH-Responsive supramolecular vesicles assembled by water-soluble pillar[5]arene and a BODIPY photosensitizer for chemo-photodynamic dual therapy. AB - Supramolecular vesicles which can successfully encapsulate DOX and exhibit rapid drug release in a low-pH environment are constructed based on the host-guest interaction of water-soluble pillar[5]arene and a BODIPY derivative. They show remarkable combination of chemo- and photodynamic activities, suggesting a promising drug nanocarrier. PMID- 26270625 TI - In vivo increase in thrombin generation by four-factor prothrombin complex concentrate in apixaban-treated healthy volunteers. AB - BACKGROUND: Four-factor prothrombin complex concentrate (PCC) (Cofact; Sanquin Blood Supply) 50 IU kg(-1) increased thrombin generation beyond baseline values in healthy, rivaroxaban-treated subjects. OBJECTIVE: To assess whether infusion with doses of 37.5 IU kg(-1) and 25 IU kg(-1) PCC reverses the anticoagulant effect of high-dose apixaban, another oral direct factor Xa inhibitor. METHODS: In a randomized, double-blind, placebo-controlled, crossover study, six healthy subjects received twice-daily apixaban 10 mg for 3.5 days followed by a single bolus of 37.5 IU kg(-1) PCC, 25 IU kg(-1) PCC, or placebo. The primary outcome was the effect of PCC 15 min after infusion on thrombin generation (endogenous thrombin potential [ETP]); secondary outcomes were the immediate effect of PCC on prothrombin time (PT) and the effect of PCC as compared with placebo over a period of 24 h on ETP and PT. RESULTS: Fifteen minutes after infusion of 37.5 IU kg(-1) and 25 IU kg(-1) PCC, ETP increased from 41% +/- 11% to 56% +/- 23% (P = 0.06) and from 44% +/- 12% to 51% +/- 15% (P = 0.03), respectively. ETP significantly differed over time between 37.5 IU kg(-1) PCC and placebo during 24 h after infusion (P < 0.01). Both PCC doses restored apixaban-induced PT prolongation after 15 min (P < 0.01), and this was sustained over a period of 24 h. CONCLUSION: Both 37.5 IU kg(-1) PCC and 25 IU/kg PCC improved coagulation parameters in healthy subjects, suggesting partial reversal of the anticoagulant effect of apixaban. This implies that PCC might be considered in patients with apixaban-associated bleeding. However, ETP was not immediately restored to pre apixaban levels, suggesting that these doses are too low to instantly and fully restore hemostasis at peak apixaban levels. PMID- 26270626 TI - Risk Factors for Advanced HIV Disease and Late Entry to HIV Care: National 1994 2012 HIV Surveillance Data for Wuhan, China. AB - Few studies in China have focused on advanced human immunodeficiency virus (HIV) disease (AHD) and late entry to HIV care, which are associated with increased morbidity and mortality. A population-based retrospective study was conducted using 980 national HIV surveillance reports from 1994 to February 2012 in Wuhan, China. AHD was defined as presence of a first-reported CD4 count<200 cells/MUL or an acquired immune deficiency syndrome (AIDS)-defining event within 1 month of HIV diagnosis. Late entry to HIV care was defined as patients with a first reported CD4 cell count>6 months after diagnosis. Non-conditional logistic regression analysis was used to identify factors associated with AHD, late entry to HIV care, and AIDS within 1 year of HIV diagnosis. The proportions of AHD, AIDS within 1 year of HIV diagnosis, and late entry to HIV care were 29.49%, 39.39%, and 20.84%, respectively. Most of the deaths (74.27%, 127/171) occurred within 1 year of diagnosis. Short-term mortality, proportion of AHD, and late entry to HIV care showed a similar downward trend from pre-2003 to 2011 (p<0.001). Age, transmission category, sample source, and occupation were associated with AHD, late entry to HIV care, and AIDS within 1 year of HIV diagnosis in the multivariate logistic regression analysis. These findings indicate that AHD and late entry to HIV care were associated with an increased incidence of AIDS or death, particularly within 1 year of diagnosis. More effort should be made to assure early diagnosis and timely entry to care. PMID- 26270630 TI - Flexible Metal-Organic Frameworks: Recent Advances and Potential Applications. AB - Flexible metal-organic frameworks (MOFs) receive much attention owing to their attractive properties that originate from their flexibility and dynamic behavior, and show great potential applications in many fields. Here, recent progress in the discovery, understanding, and property investigations of flexible MOFs are reviewed, and the examples of their potential applications in storage and separation, sensing, and guest capture and release are presented to highlight the developing trends in flexible MOFs. PMID- 26270627 TI - Resting state in Parkinson's disease dementia and dementia with Lewy bodies: commonalities and differences. AB - OBJECTIVE: Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are two dementias with overlapping phenotypes. Clinically, these are differentiated by the one-year precedence rule between the onset of dementia with respect to Parkinsonism. In this report we aimed to find differences between DLB and PDD in functional connectivity (FC) using resting state functional magnetic resonance imaging, which we hypothesised would reflect the underlying pathological differences between DLB and PDD. METHODS: The study cohort comprised of 18 patients with DLB, 12 with PDD and 17 healthy control (HC) groups. Eight cortical and four subcortical seeds were chosen, and time series extracted to estimate correlation maps. We also implemented a voxel-based morphometry (VBM) analysis to assess regional grey matter differences. FC analysis was corrected for age, sex and regional grey matter differences. RESULTS: The FC analysis showed greater alterations in DLB than in PDD for seeds placed within the fronto parietal network (FPN), whilst in contrast, for the supplementary motor area seed FC alterations were more apparent in PDD than in DLB. However, when comparing DLB and PDD, no significant differences were found. In addition, VBM analysis revealed greater atrophy in PDD than HC and DLB in the bilateral motor cortices and precuneus respectively. CONCLUSIONS: PDD and DLB demonstrate similar FC alterations in the brain. However, attention- and motor-related seeds revealed subtle differences between both conditions when compared with HC, which may relate to the neuropathology and chronological precedence of core symptoms in the Lewy body dementias. PMID- 26270629 TI - Analysis of carbohydrates and glycoconjugates by matrix-assisted laser desorption/ionization mass spectrometry: An update for 2011-2012. AB - This review is the seventh update of the original article published in 1999 on the application of MALDI mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2012. General aspects such as theory of the MALDI process, matrices, derivatization, MALDI imaging, and fragmentation are covered in the first part of the review and applications to various structural types constitute the remainder. The main groups of compound are oligo- and poly-saccharides, glycoproteins, glycolipids, glycosides, and biopharmaceuticals. Much of this material is presented in tabular form. Also discussed are medical and industrial applications of the technique, studies of enzyme reactions, and applications to chemical synthesis. (c) 2015 Wiley Periodicals, Inc. Mass Spec Rev 36:255-422, 2017. PMID- 26270628 TI - Bioactive electrospun fibers of poly(glycerol sebacate) and poly(epsilon caprolactone) for cardiac patch application. AB - Scaffolds for cardiac patch application must meet stringent requirements such as biocompatibility, biodegradability, and facilitate vascularization in the engineered tissue. Here, a bioactive, biocompatible, and biodegradable electrospun scaffold of poly(glycerol sebacate)-poly(epsilon-caprolactone) (PGS PCL) is proposed as a potential scaffold for cardiac patch application. The fibers are smooth bead free with average diameter = 0.8 +/- 0.3 MUm, mean pore size = 2.2 +/- 1.2 MUm, porosity = 62 +/- 4%, and permeability higher than that of control biological tissue. For the first time, bioactive PGS-PCL fibers functionalized with vascular endothelial growth factor (VEGF) are developed, the approach used being chemical modification of the PGS-PCL fibers followed by subsequent binding of VEGF via amide bonding. The approach results in uniform immobilization of VEGF on the fibers; the concentrations are 1.0 MUg cm(-2) for the PGS-PCL (H) and 0.60 MUg cm(-2) for the PGS-PCL (L) samples. The bioactive scaffold supports the attachment and growth of seeded myogenic and vasculogenic cell lines. In fact, rat aortic endothelial cells also display angiogenic features indicating potential for the formation of vascular tree in the scaffold. These results therefore demonstrate the prospects of VEGF-functionalized PGS-PCL fibrous scaffold as promising matrix for cardiac patch application. PMID- 26270631 TI - 16S rRNA Gene Sequence-Based Identification of Bacteria in Automatically Incubated Blood Culture Materials from Tropical Sub-Saharan Africa. AB - BACKGROUND: The quality of microbiological diagnostic procedures depends on pre analytic conditions. We compared the results of 16S rRNA gene PCR and sequencing from automatically incubated blood culture materials from tropical Ghana with the results of cultural growth after automated incubation. METHODS: Real-time 16S rRNA gene PCR and subsequent sequencing were applied to 1500 retained blood culture samples of Ghanaian patients admitted to a hospital with an unknown febrile illness after enrichment by automated culture. RESULTS: Out of all 1500 samples, 191 were culture-positive and 98 isolates were considered etiologically relevant. Out of the 191 culture-positive samples, 16S rRNA gene PCR and sequencing led to concordant results in 65 cases at species level and an additional 62 cases at genus level. PCR was positive in further 360 out of 1309 culture-negative samples, sequencing results of which suggested etiologically relevant pathogen detections in 62 instances, detections of uncertain relevance in 50 instances, and DNA contamination due to sample preparation in 248 instances. In two instances, PCR failed to detect contaminants from the skin flora that were culturally detectable. Pre-analytical errors caused many Enterobacteriaceae to be missed by culture. CONCLUSIONS: Potentially correctable pre-analytical conditions and not the fastidious nature of the bacteria caused most of the discrepancies. Although 16S rRNA gene PCR and sequencing in addition to culture led to an increase in detections of presumably etiologically relevant blood culture pathogens, the application of this procedure to samples from the tropics was hampered by a high contamination rate. Careful interpretation of diagnostic results is required. PMID- 26270633 TI - Superficial Postauricular Mass in an Infant. PMID- 26270634 TI - Procedures Performed by Emergency Medical Services in the United States. AB - Emergency medical services (EMS) must provide a wide range of care for patients in the out-of-hospital setting. Although previous work has detailed that EMS providers rarely perform certain procedures, (e.g., endotracheal intubation) there are limited data detailing the frequency of procedures across the breadth of EMS providers' scope of practice. We sought to characterize procedures performed by EMS in the United States. We conducted an analysis of the 2011 National Emergency Medical Services Information System (NEMSIS) research data set, encompassing EMS emergency response data from 40 states and two territories. From these data, we report the number and incidence of EMS procedures. We also characterize procedures performed. There were 14,371,941 submitted EMS responses, of which 7,680,559 had complete information on procedures performed on adults. Of these, 4,206,360 EMS responses had procedures performed totaling 11,407,396 procedures. The most common procedures performed were peripheral venous access (28.4%), cardiac monitoring (16.1%) pulse oximetry (13.5%), and blood glucose analysis (10.4%). Procedures were performed most often in patients with traumatic injury (20.0%) followed by chest pain/discomfort (14.0%). Critical procedures (cardioversion, defibrillation, endotracheal intubation, etc.) were infrequently performed (n = 277,785, 2.4%). These data highlight the frequency with which EMS providers perform procedures across the United States. This may help to guide future EMS training and education efforts by highlighting the relative frequency and infrequency of specific procedures. PMID- 26270637 TI - Buckwheat as a Functional Food and Its Effects on Health. AB - Buckwheat (BW) is a gluten-free pseudocereal that belongs to the Polygonaceae family. BW grain is a highly nutritional food component that has been shown to provide a wide range of beneficial effects. Health benefits attributed to BW include plasma cholesterol level reduction, neuroprotection, anticancer, anti inflammatory, antidiabetic effects, and improvement of hypertension conditions. In addition, BW has been reported to possess prebiotic and antioxidant activities. In vitro and animal studies suggest that BW's bioactive compounds, such as D-chiro-inositol (DCI), BW proteins (BWP), and BW flavonoids (mainly rutin and quercetin) may be partially responsible for the observed effects. The purpose of this paper is to review the recent research regarding the health benefits of BW, in vitro and in vivo, focusing on the specific role of its bioactive compounds and on the mechanisms by which these effects are exerted. PMID- 26270632 TI - Systematic Evaluation of Bioorthogonal Reactions in Live Cells with Clickable HaloTag Ligands: Implications for Intracellular Imaging. AB - Bioorthogonal reactions, including the strain-promoted azide-alkyne cycloaddition (SPAAC) and inverse electron demand Diels-Alder (iEDDA) reactions, have become increasingly popular for live-cell imaging applications. However, the stability and reactivity of reagents has never been systematically explored in the context of a living cell. Here we report a universal, organelle-targetable system based on HaloTag protein technology for directly comparing bioorthogonal reagent reactivity, specificity, and stability using clickable HaloTag ligands in various subcellular compartments. This system enabled a detailed comparison of the bioorthogonal reactions in live cells and informed the selection of optimal reagents and conditions for live-cell imaging studies. We found that the reaction of sTCO with monosubstituted tetrazines is the fastest reaction in cells; however, both reagents have stability issues. To address this, we introduced a new variant of sTCO, Ag-sTCO, which has much improved stability and can be used directly in cells for rapid bioorthogonal reactions with tetrazines. Utilization of Ag complexes of conformationally strained trans-cyclooctenes should greatly expand their usefulness especially when paired with less reactive, more stable tetrazines. PMID- 26270638 TI - Modeling the Dependency Structure of Integrated Intensity Processes. AB - This paper studies an important issue of dependence structure. To model this structure, the intensities within the Cox processes are driven by dependent shot noise processes, where jumps occur simultaneously and their sizes are correlated. The joint survival probability of the integrated intensities is explicitly obtained from the copula with exponential marginal distributions. Subsequently, this result can provide a very useful guide for credit risk management. PMID- 26270639 TI - Oscarella lobularis (Homoscleromorpha, Porifera) Regeneration: Epithelial Morphogenesis and Metaplasia. AB - Sponges are known to possess remarkable reconstitutive and regenerative abilities ranging from common wounding or body part regeneration to more impressive re building of a functional body from dissociated cells. Among the four sponge classes, Homoscleromorpha is notably the only sponge group to possess morphologically distinct basement membrane and specialized cell-junctions, and is therefore considered to possess true epithelia. The consequence of this peculiar organization is the predominance of epithelial morphogenesis during ontogenesis of these sponges. In this work we reveal the underlying cellular mechanisms used during morphogenesis accompanying ectosome regeneration in the homoscleromorph sponge model: Oscarella lobularis. We identified three main sources of novel exopinacoderm during the processes of its regeneration and the restoration of functional peripheral parts of the aquiferous system in O. lobularis: (1) intact exopinacoderm surrounding the wound surface, (2) the endopinacoderm from peripheral exhalant and inhalant canals, and (3) the intact choanoderm found on the wound surface. The basic morphogenetic processes during regeneration are the spreading and fusion of epithelial sheets that merge into one continuous epithelium. Transdifferentiation of choanocytes into exopinacocytes is also present. Epithelial-mesenchymal transition is absent during regeneration. Moreover, we cannot reveal any other morphologically distinct pluripotent cells. In Oscarella, neither blastema formation nor local dedifferentiation and proliferation have been detected, which is probably due to the high morphogenetic plasticity of the tissue. Regeneration in O. lobularis goes through cell transdifferentiation and through the processes, when lost body parts are replaced by the remodeling of the remaining tissue. Morphogenesis during ectosome regeneration in O. lobularis is correlated with its true epithelial organization. Knowledge of the morphological basis of morphogenesis during Oscarella regeneration could have important implications for our understanding of the diversity and evolution of regeneration mechanisms in metazoans, and is a strong basis for future investigations with molecular-biological approaches. PMID- 26270640 TI - Late Recurrence of Rheumatic Fever. PMID- 26270643 TI - Correction: Association of Sarcopenic Obesity with Higher Serum High-Sensitivity C-Reactive Protein Levels in Chinese Older Males-A Community-Based Study (Taichung Community Health Study-Elderly, TCHS-E). PMID- 26270641 TI - Low Serum Hepcidin in Patients with Autoimmune Liver Diseases. AB - Hepcidin, a liver hormone, is important for both innate immunity and iron metabolism regulation. As dysfunction of the hepcidin pathway may contribute to liver pathology, we analysed liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases. Hepcidin mRNA levels were determined in liver biopsies obtained from 126 patients with HCV (n = 21), HBV (n = 23), autoimmune cholestatic disease (primary biliary cirrhosis and primary sclerosing cholangitis; PBC/PSC; n = 34), autoimmune hepatitis (AIH; n = 16) and non alcoholic fatty liver disease (NAFLD; n = 32). Sera sampled on the biopsy day from the same patients were investigated for serum hepcidin levels. Hepatic hepcidin mRNA levels correlated positively with ferritin and negatively with serum gamma-GT levels. However, no correlation was found between serum hepcidin and either ferritin or liver hepcidin mRNA. Both serum hepcidin and the serum hepcidin/ferritin ratio were significantly lower in AIH and PBC/PSC patients' sera compared to HBV, HCV or NAFLD (P<0.001 for each comparison) and correlated negatively with serum ALP levels. PBC/PSC and AIH patients maintained low serum hepcidin during the course of their two-year long treatment. In summary, parallel determination of liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases shows that circulating hepcidin and its respective ratio to ferritin are significantly diminished in patients with autoimmune liver diseases. These novel findings, once confirmed by follow-up studies involving bigger size and better-matched disease subgroups, should be taken into consideration during diagnosis and treatment of autoimmune liver diseases. PMID- 26270646 TI - Grandparent caregiving among rural African Americans in a community in the American South: challenges to health and wellbeing. AB - INTRODUCTION: An increasing number of grandparents in rural USA are serving as primary caregivers for their grandchildren because of parental incarceration, addiction, joblessness, or illness. Low-income, African American women from the South are overrepresented in this growing population. There is a paucity of research exploring the challenges faced by rural grandparent caregivers, and past studies have not explicitly addressed the potential consequences of rural grandparent caregiving for health. The purpose of this qualitative study was to explore grandparent caregiving among rural, low-income, African American grandmothers in a community in the American South, and to identify challenges to health that arose in that context. McLeroy's social ecological model (SEM) was used to examine these challenges at multiple levels of influence. METHODS: This qualitative interview-based study was conducted in a high-poverty community in rural Georgia. In-depth interviews were conducted with African American grandparent caregivers and key informants from local community-based organizations. A key informant assisted in identifying initial interview participants, and then snowball sampling was used to recruit additional participants. Interview questions were grouped under five domains (intrapersonal, interpersonal, community, organizational, and policy), according to the levels of the SEM. Iterative content analysis of interview transcripts was utilized. Transcripts were coded to identify text segments related to each domain of the SEM, which were grouped together for analysis by domain. Reflexive memo-writing aided in development of themes, and data quality was assessed using Lincoln and Guba's trustworthiness criteria. RESULTS: Rural African American grandparent caregivers faced a range of challenges to health. Direct physical challenges included chronic pain that interfered with sleep and daily functioning, mobility issues exacerbated by child care, and the pressure of managing their own medical conditions as well as their grandchildren's. Financial scarcity added to their vulnerability to poor health outcomes, especially when caregivers would forego purchase of medications or visits to the doctor because of expenses related to their grandchildren. In addition, lack of child care made health appointments and hospitalizations logistically difficult. Emotional strain was common as grandparent caregivers struggled to protect their grandchildren in communities where rates of drug use, HIV, and incarceration were high. Caregivers worried about their mortality and the related consequences for their grandchildren. Chronic stress, which is linked to a number of poor health outcomes, was self reported by most rural grandparent caregivers. CONCLUSIONS: In this study, the challenges of rural grandparent caregiving among African American women posed multiple threats to health and wellbeing. Further research is needed, in different rural contexts and with different caregiver populations, to more thoroughly examine the health risks of grandparent caregiving. In addition, the development of multi-faceted interventions and programs will be critical to meeting the needs of rural grandparent caregivers. A few models for such programs exist, although resource shortfalls have often limited their impact. PMID- 26270645 TI - Human Neural Cells Transiently Express Reelin during Olfactory Placode Development. AB - Reelin, an extracellular glycoprotein is essential for migration and correct positioning of neurons during development. Since the olfactory system is known as a source of various migrating neuronal cells, we studied Reelin expression in the two chemosensory olfactory systems, main and accessory, during early developmental stages of human foetuses/embryos from Carnegie Stage (CS) 15 to gestational week (GW) 14. From CS 15 to CS 18, but not at later stages, a transient expression of Reelin was detected first in the presumptive olfactory and then in the presumptive vomeronasal epithelium. During the same period, Reelin-positive cells detach from the olfactory/vomeronasal epithelium and migrate through the mesenchyme beneath the telencephalon. Dab 1, an adaptor protein of the Reelin pathway, was simultaneously expressed in the migratory mass from CS16 to CS17 and, at later stages, in the presumptive olfactory ensheathing cells. Possible involvements of Reelin and Dab 1 in the peripheral migrating stream are discussed. PMID- 26270642 TI - Integrative Analysis of MicroRNA and mRNA Data Reveals an Orchestrated Function of MicroRNAs in Skeletal Myocyte Differentiation in Response to TNF-alpha or IGF1. AB - INTRODUCTION: Skeletal muscle cell differentiation is impaired by elevated levels of the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) with pathological significance in chronic diseases or inherited muscle disorders. Insulin like growth factor-1 (IGF1) positively regulates muscle cell differentiation. Both, TNF-alpha and IGF1 affect gene and microRNA (miRNA) expression in this process. However, computational prediction of miRNA-mRNA relations is challenged by false positives and targets which might be irrelevant in the respective cellular transcriptome context. Thus, this study is focused on functional information about miRNA affected target transcripts by integrating miRNA and mRNA expression profiling data. METHODOLOGY/PRINCIPAL FINDINGS: Murine skeletal myocytes PMI28 were differentiated for 24 hours with concomitant TNF alpha or IGF1 treatment. Both, mRNA and miRNA expression profiling was performed. The data-driven integration of target prediction and paired mRNA/miRNA expression profiling data revealed that i) the quantity of predicted miRNA-mRNA relations was reduced, ii) miRNA targets with a function in cell cycle and axon guidance were enriched, iii) differential regulation of anti-differentiation miR-155-5p and miR-29b-3p as well as pro-differentiation miR-335-3p, miR-335-5p, miR-322-3p, and miR-322-5p seemed to be of primary importance during skeletal myoblast differentiation compared to the other miRNAs, iv) the abundance of targets and affected biological processes was miRNA specific, and v) subsets of miRNAs may collectively regulate gene expression. CONCLUSIONS: Joint analysis of mRNA and miRNA profiling data increased the process-specificity and quality of predicted relations by statistically selecting miRNA-target interactions. Moreover, this study revealed miRNA-specific predominant biological implications in skeletal muscle cell differentiation and in response to TNF-alpha or IGF1 treatment. Furthermore, myoblast differentiation-associated miRNAs are suggested to collectively regulate gene clusters and targets associated with enriched specific gene ontology terms or pathways. Predicted miRNA functions of this study provide novel insights into defective regulation at the transcriptomic level during myocyte proliferation and differentiation due to inflammatory stimuli. PMID- 26270647 TI - Evaluation of Nine Consensus Indices in Delphi Foresight Research and Their Dependency on Delphi Survey Characteristics: A Simulation Study and Debate on Delphi Design and Interpretation. AB - The extent of consensus (or the lack thereof) among experts in emerging fields of innovation can serve as antecedents of scientific, societal, investor and stakeholder synergy or conflict. Naturally, how we measure consensus is of great importance to science and technology strategic foresight. The Delphi methodology is a widely used anonymous survey technique to evaluate consensus among a panel of experts. Surprisingly, there is little guidance on how indices of consensus can be influenced by parameters of the Delphi survey itself. We simulated a classic three-round Delphi survey building on the concept of clustered consensus/dissensus. We evaluated three study characteristics that are pertinent for design of Delphi foresight research: (1) the number of survey questions, (2) the sample size, and (3) the extent to which experts conform to group opinion (the Group Conformity Index) in a Delphi study. Their impacts on the following nine Delphi consensus indices were then examined in 1000 simulations: Clustered Mode, Clustered Pairwise Agreement, Conger's Kappa, De Moivre index, Extremities Version of the Clustered Pairwise Agreement, Fleiss' Kappa, Mode, the Interquartile Range and Pairwise Agreement. The dependency of a consensus index on the Delphi survey characteristics was expressed from 0.000 (no dependency) to 1.000 (full dependency). The number of questions (range: 6 to 40) in a survey did not have a notable impact whereby the dependency values remained below 0.030. The variation in sample size (range: 6 to 50) displayed the top three impacts for the Interquartile Range, the Clustered Mode and the Mode (dependency = 0.396, 0.130, 0.116, respectively). The Group Conformity Index, a construct akin to measuring stubbornness/flexibility of experts' opinions, greatly impacted all nine Delphi consensus indices (dependency = 0.200 to 0.504), except the Extremity CPWA and the Interquartile Range that were impacted only beyond the first decimal point (dependency = 0.087 and 0.083, respectively). Scholars in technology design, foresight research and future(s) studies might consider these new findings in strategic planning of Delphi studies, for example, in rational choice of consensus indices and sample size, or accounting for confounding factors such as experts' variable degrees of conformity (stubbornness/flexibility) in modifying their opinions. PMID- 26270644 TI - Distribution, Numbers, and Diversity of ESBL-Producing E. coli in the Poultry Farm Environment. AB - This study aimed to discern the contribution of poultry farms to the contamination of the environment with ESBL-producing Escherichia coli and therewith, potentially to the spread of these bacteria to humans and other animals. ESBL-producing E. coli were detected at all investigated laying hen farms (n = 5) and broiler farms (n = 3) in 65% (46/71) and 81% (57/70) of poultry faeces samples, respectively. They were detected in rinse water and run-off water (21/26; 81%), other farm animals (11/14; 79%), dust (21/35; 60%), surface water adjacent to farms (20/35; 57%), soil (48/87; 55%), on flies (11/73; 15%), and in barn air (2/33; 6%). The highest prevalence and concentrations in the outdoor environment were observed in soil of free-range areas at laying hen farms (100% of samples positive, geometric mean concentration 2.4*10(4) cfu/kg), and surface waters adjacent to broiler farms during, or shortly after, cleaning between production rounds (91% of samples positive, geometric mean concentration 1.9*10(2) cfu/l). The diversity of ESBL-producing E. coli variants with respect to sequence type, phylogenetic group, ESBL-genotype and antibiotic resistance profile was high, especially on broiler farms where on average 16 different variants were detected, and the average Simpson's Indices of diversity (SID; 1-D) were 0.93 and 0.94 among flock and environmental isolates respectively. At laying hen farms on average nine variants were detected, with SIDs of 0.63 (flock isolates) and 0.77 (environmental isolates). Sixty percent of environmental isolates were identical to flock isolates at the same farm. The highest proportions of 'flock variants' were observed in dust (94%), run-off gullies (82%), and barn air (67%), followed by surface water (57%), soil (56%), flies (50%) and other farm animals (35%).The introduction of ESBL-producing E. coli from poultry farms to the environment may pose a health risk if these bacteria reach places where people may become exposed. PMID- 26270648 TI - Can Population-Level Laterality Stem from Social Pressures? Evidence from Cheek Kissing in Humans. AB - Despite extensive research, the origins and functions of behavioural laterality remain largely unclear. One of the most striking unresolved issues is the fact that laterality generally occurs at the population-level. Why would the majority of the individuals of a population exhibit the same laterality, while individual level laterality would yet provide the advantages in terms of improving behavioural efficiency? Are social pressures the key factor? Can social pressures induce alignment of laterality between the individuals of a population? Can the effect of social pressures overpass the effect of other possible determining factors (e.g. genes)? We tested this important new hypothesis in humans, for the first time. We asked whether population-level laterality could stem from social pressures. Namely, we assessed social pressures on laterality in an interactive social behaviour: kissing on the cheek as a greeting. We performed observations in 10 cities of France. The observations took place in spots where people of the city meet and greet each other. We showed that: a) there is a population-level laterality for cheek kissing, with the majority of individuals being aligned in each city, and b) there is a variation between populations, with a laterality that depends on the city. These results were confirmed by our complementary data from questionnaires and internet surveys. These findings show that social pressures are involved in determining laterality. They demonstrate that population-level laterality can stem from social pressures. PMID- 26270650 TI - Chemoenzymatic Synthesis of (+)-Asperpentyn and the Enantiomer of the Structure Assigned to Aspergillusol A. AB - Total syntheses of (+)-asperpentyn (1) and compound ent-2, the enantiomer of the structure, 2, assigned to the natural product aspergillusol A are reported. Both reaction sequences employ the enzymatically derived and enantiomerically pure cis 1,2-dihydrocatechol 4 as starting material and use Sonogashira cross-coupling chemistry to install the required enyne side-chain. The (1)H and (13)C NMR spectroscopic data derived from compound ent-2 match those reported for aspergillusol A, thus suggesting that the gross structure of this natural product has been assigned correctly, although its absolute stereochemistry remains unclear. PMID- 26270651 TI - Irreversible Electroporation of Malignant Hepatic Tumors--Alterations in Venous Structures at Subacute Follow-Up and Evolution at Mid-Term Follow-Up. AB - PURPOSE: To evaluate risk factors associated with alterations in venous structures adjacent to an ablation zone after percutaneous irreversible electroporation (IRE) of hepatic malignancies at subacute follow-up (1 to 3 days after IRE) and to describe evolution of these alterations at mid-term follow-up. MATERIALS AND METHODS: 43 patients (men/women, 32/11; mean age, 60.3 years) were identified in whom venous structures were located within a perimeter of 1.0 cm of the ablation zone at subacute follow-up after IRE of 84 hepatic lesions (primary/secondary hepatic tumors, 31/53). These vessels were retrospectively evaluated by means of pre-interventional and post-interventional contrast enhanced magnetic resonance imaging or computed tomography or both. Any vascular changes in flow, patency, and diameter were documented. Correlations between vascular change (yes/no) and characteristics of patients, lesions, and ablation procedures were assessed by generalized linear models. RESULTS: 191 venous structures were located within a perimeter of 1.0 cm of the ablation zone: 55 (29%) were encased by the ablation zone, 78 (41%) abutted the ablation zone, and 58 (30%) were located between 0.1 and 1.0 cm from the border of the ablation zone. At subacute follow-up, vascular changes were found in 19 of the 191 vessels (9.9%), with partial portal vein thrombosis in 2, complete portal vein thrombosis in 3, and lumen narrowing in 14 of 19. At follow-up of patients with subacute vessel alterations (mean, 5.7 months; range, 0 to 14 months) thrombosis had resolved in 2 of 5 cases; vessel narrowing had completely resolved in 8 of 14 cases, and partly resolved in 1 of 14 cases. The encasement of a vessel by ablation zone (OR = 6.36, p<0.001), ablation zone being adjacent to a portal vein (OR = 8.94, p<0.001), and the usage of more than 3 IRE probes (OR = 3.60, p = 0.035) were independently associated with post-IRE vessel alterations. CONCLUSION: Venous structures located in close proximity to an IRE ablation zone remain largely unaffected by this procedure, and thrombosis is rare. PMID- 26270649 TI - Predicting Hemagglutinin MHC-II Ligand Analogues in Anti-TNFalpha Biologics: Implications for Immunogenicity of Pharmaceutical Proteins. AB - The purpose of this study was to evaluate the extent of overlapping immunogenic peptides between three pharmaceutical biologics and influenza viruses. Clinical studies have shown that subsets of patients with rheumatoid arthritis (RA) develop anti-drug antibodies towards anti-TNFalpha biologics. We postulate that common infectious pathogens, including influenza viruses, may sensitize RA patients toward recombinant proteins. We hypothesize that embedded within infliximab (IFX), adalimumab (ADA), and etanercept (ETN) are ligands of class II major histocompatibility complex (MHC-II) that mimic T cell epitopes derived from influenza hemagglutinin (HA). The rationale is that repeated administration of the biologics would reactivate HA-primed CD4 T cells, stimulating B cells to produce cross-reactive antibodies. Custom scripts were constructed using MATLAB to compare MHC-II ligands of HA and the biologics; all ligands were predicted using tools in Immune Epitope Database and Resources (IEDB). We analyzed three HLA-DR1 alleles (0101, 0401 and 1001) that are prominent in RA patients, and two alleles (0103 and 1502) that are not associated with RA. The results indicate that 0401 would present more analogues of HA ligands in the three anti-TNFalpha biologics compared to the other alleles. The approach led to identification of potential ligands in IFX and ADA that shares sequence homology with a known HA specific CD4 T cell epitope. We also discovered a peptide in the complementarity determining region 3 (CDR-3) of ADA that encompasses both a potential CD4 T cell epitope and a known B cell epitope in HA. The results may help generate new hypotheses for interrogating patient variability of immunogenicity of the anti TNFalpha drugs. The approach would aid development of new recombinant biologics by identifying analogues of CD4 T cell epitopes of common pathogens at the preclinical stage. PMID- 26270652 TI - High ABCG4 Expression Is Associated with Poor Prognosis in Non-Small-Cell Lung Cancer Patients Treated with Cisplatin-Based Chemotherapy. AB - ATP-binding cassette (ABC) transporters are associated with poor response to chemotherapy, and confer a poor prognosis in various malignancies. However, the association between the expression of the ABC sub-family G member 4 (ABCG4) and prognosis in patients with non-small-cell lung cancer (NSCLC) remains unclear. NSCLC tissue samples (n = 140) and normal lung tissue samples (n = 90) were resected from patients with stage II to IV NSCLC between May 2004 and May 2009. ABCG4 mRNA and protein expressions were detected by RT-PCR, western blot, and immunohistochemistry. Patients received four cycles of cisplatin-based post surgery chemotherapy and were followed up until May 31st, 2014. ABCG4 positivity rate was higher in NSCLC than in normal lung tissues (48.6% vs. 0%, P<0.001) and ABCG4 expression was significantly associated with poor differentiation, higher tumor node metastasis (TNM) stage, and adenocarcinoma histological type (all P<0.001). Univariate (HR = 2.284, 95%CI: 1.570-3.324, P<0.001) and multivariate (HR = 2.236, 95%CI: 1.505-3.321, P<0.001) analyses showed that ABCG4 expression was an independent factor associated with a poor prognosis in NSCLC. Patients with ABCG4-positive NSCLC had shorter median survival than ABCG4-negative NSCLC (20.1 vs. 43.2 months, P<0.001). The prognostic significance of ABCG4 expression was apparent in stages III and IV NSCLC. In conclusion, high ABCG4 expression was associated with a poor prognosis in patients with NSCLC treated with cisplatin based chemotherapy. PMID- 26270653 TI - Glutamine Synthetase Sensitivity to Oxidative Modification during Nutrient Starvation in Prochlorococcus marinus PCC 9511. AB - Glutamine synthetase plays a key role in nitrogen metabolism, thus the fine regulation of this enzyme in Prochlorococcus, which is especially important in the oligotrophic oceans where this marine cyanobacterium thrives. In this work, we studied the metal-catalyzed oxidation of glutamine synthetase in cultures of Prochlorococcus marinus strain PCC 9511 subjected to nutrient limitation. Nitrogen deprivation caused glutamine synthetase to be more sensitive to metal catalyzed oxidation (a 36% increase compared to control, non starved samples). Nutrient starvation induced also a clear increase (three-fold in the case of nitrogen) in the concentration of carbonyl derivatives in cell extracts, which was also higher (22%) upon addition of the inhibitor of electron transport, DCMU, to cultures. Our results indicate that nutrient limitations, representative of the natural conditions in the Prochlorococcus habitat, affect the response of glutamine synthetase to oxidative inactivating systems. Implications of these results on the regulation of glutamine synthetase by oxidative alteration prior to degradation of the enzyme in Prochlorococcus are discussed. PMID- 26270654 TI - Effect of Ozone Treatment on Nano-Sized Silver Sulfide in Wastewater Effluent. AB - Silver nanoparticles used in consumer products are likely to be released into municipal wastewater. Transformation reactions, most importantly sulfidation, lead to the formation of nanoscale silver sulfide (nano-Ag2S) particles. In wastewater treatment plants (WWTP), ozonation can enhance the effluent quality by eliminating organic micropollutants. The effect of ozonation on the fate of nano Ag2S, however, is currently unknown. In this study, we investigate the interaction of ozone with nano-Ag2S and evaluate the effect of ozonation on the short-term toxicity of WWTP effluent spiked with nano-Ag2S. The oxidation of nano Ag2S by ozone resulted in a stoichiometric factor (number of moles of ozone required to oxidize one mole of sulfide to sulfate) of 2.91, which is comparable to the results obtained for the reaction of bisulfide (HS(-)) with ozone. The second-order rate constant for the reaction of nano-Ag2S with ozone (k = 3.1 * 10(4) M(-1) s(-1)) is comparable to the rate constant of fast-reacting micropollutants. Analysis of the ozonation products of nano-Ag2S by transmission electron microscopy (TEM) and X-ray absorption spectroscopy (XAS) revealed that ozonation dominantly led to the formation of silver chloride in WWTP effluent. After ozonation of the Ag2S-spiked effluent, the short-term toxicity for the green algae Chlamydomonas reinhardtii increased and reached EC50 values comparable to Ag(+). This study thus reveals that ozone treatment of WWTP effluent results in the oxidation of Ag2S and, hence, an increase of the Ag toxicity in the effluent, which may become relevant at elevated Ag concentrations. PMID- 26270655 TI - Innate-like lymphocytes in intestinal infections. AB - PURPOSE OF REVIEW: The mechanisms of immunity against intestinal pathogens are not well understood. Innate-like lymphocytes are a group of recently discovered cells that do not fit into either side of the historical innate-adaptive classification. They are enriched in the intestinal mucosa and participate in gut homeostasis and defense against infections. We will review recent developments in innate-like T lymphocytes and innate lymphoid cells, specifically as they relate to responses to intestinal infections. RECENT FINDINGS: Recent studies have uncovered further details into antigen presentation to gammadelta T cells and mucosal-associated invariant T cells, the role of invariant natural killer T cells and mucosal-associated invariant T cells in intestinal infections, and how innate lymphoid cells maintain gut homeostasis and protection. SUMMARY: Innate like lymphocytes play a major role in the critical early response to intestinal infections and maintaining gut homeostasis. Further studies of the roles these cells play in the human intestinal mucosa will aid in the development of therapeutics against intestinal infections. PMID- 26270657 TI - Neuroprotective Effects of Mitochondria-Targeted Plastoquinone and Thymoquinone in a Rat Model of Brain Ischemia/Reperfusion Injury. AB - We explored the neuroprotective properties of natural plant-derived antioxidants plastoquinone and thymoquinone (2-demethylplastoquinone derivative) modified to be specifically accumulated in mitochondria. The modification was performed through chemical conjugation of the quinones with penetrating cations: Rhodamine 19 or tetraphenylphosphonium. Neuroprotective properties were evaluated in a model of middle cerebral artery occlusion. We demonstrate that the mitochondria targeted compounds, introduced immediately after reperfusion, possess various neuroprotective potencies as judged by the lower brain damage and higher neurological status. Plastoquinone derivatives conjugated with rhodamine were the most efficient, and the least efficiency was shown by antioxidants conjugated with tetraphenylphosphonium. Antioxidants were administered intraperitoneally or intranasally with the latter demonstrating a high level of penetration into the brain tissue. The therapeutic effects of both ways of administration were similar. Long-term administration of antioxidants in low doses reduced the neurological deficit, but had no effect on the volume of brain damage. At present, cationic decylrhodamine derivatives of plastoquinone appear to be the most promising anti-ischemic mitochondria-targeted drugs of the quinone family. We suggest these antioxidants could be potentially used for a stroke treatment. PMID- 26270656 TI - A Chinese cave links climate change, social impacts, and human adaptation over the last 500 years. AB - The collapse of some pre-historical and historical cultures, including Chinese dynasties were presumably linked to widespread droughts, on the basis of synchronicities of societal crises and proxy-based climate events. Here, we present a comparison of ancient inscriptions in Dayu Cave from Qinling Mountains, central China, which described accurate times and detailed impacts of seven drought events during the period of 1520-1920 CE, with high-resolution speleothem records from the same cave. The comparable results provide unique and robust tests on relationships among speleothem delta(18)O changes, drought events, and societal unrest. With direct historical evidences, our results suggest that droughts and even modest events interrupting otherwise wet intervals can cause serious social crises. Modeling results of speleothem delta(18)O series suggest that future precipitation in central China may be below the average of the past 500 years. As Qinling Mountain is the main recharge area of two large water transfer projects and habitats of many endangered species, it is imperative to explore an adaptive strategy for the decline in precipitation and/or drought events. PMID- 26270659 TI - LincRNA-p21: Implications in Human Diseases. AB - Long noncoding RNAs (lncRNAs), which lack significant protein-coding capacity, regulate various biological processes through diverse and as yet poorly understood molecular mechanisms. However, a number of studies in the past few years have documented important functions for lncRNAs in human diseases. Among these lncRNAs, lincRNA-p21 has been proposed to be a novel regulator of cell proliferation, apoptosis and DNA damage response, and involved in the initiation and progression of human diseases. In this review, we summarize the current knowledge of lincRNA-p21, mainly focus on the known biological functions and its underlying mechanisms. Moreover, we highlight the growing body of evidences for the importance of lincRNA-p21 in diverse human diseases, which indicate lincRNA p21 as a potential diagnostic marker and/or a valuable therapeutic target for these diseases. PMID- 26270658 TI - Salvia miltiorrhiza Induces Tonic Contraction of the Lower Esophageal Sphincter in Rats via Activation of Extracellular Ca2+ Influx. AB - Up to 40% of patients with gastroesophageal reflux disease (GERD) suffer from proton pump inhibitor refractory GERD but clinically the medications to strengthen the lower esophageal sphincter (LES) to avoid irritating reflux are few in number. This study aimed to examine whether Salvia miltiorrhiza (SM) extracts induce tonic contraction of rat LES ex vivo and elucidate the underlying mechanisms. To investigate the mechanism underlying the SM extract-induced contractile effects, rats were pretreated with atropine (a muscarinic receptor antagonist), tetrodotoxin (a sodium channel blocker), nifedipine (a calcium channel blocker), and Ca(2+)-free Krebs-Henseleit solution with ethylene glycol tetraacetic acid (EGTA), followed by administration of cumulative dosages of SM extracts. SM extracts induced dose-related tonic contraction of the LES, which was unaffected by tetrodotoxin, atropine, or nifedipine. However, the SM extract induced LES contraction was significantly inhibited by Ca(2+)-free Krebs Henseleit solution with EGTA. Next, SM extracts significantly induce extracellular Ca(2+) entry into primary LES cells in addition to intracellular Ca(2+) release and in a dose-response manner. Confocal fluorescence microscopy showed that the SM extracts consistently induced significant extracellular Ca(2+) influx into primary LES cells in a time-dependent manner. In conclusion, SM extracts could induce tonic contraction of LES mainly through the extracellular Ca(2+) influx pathway. PMID- 26270660 TI - In Vitro Expansion of CAG, CAA, and Mixed CAG/CAA Repeats. AB - Polyglutamine diseases, including Huntington's disease and a number of spinocerebellar ataxias, are caused by expanded CAG repeats that are located in translated sequences of individual, functionally-unrelated genes. Only mutant proteins containing polyglutamine expansions have long been thought to be pathogenic, but recent evidence has implicated mutant transcripts containing long CAG repeats in pathogenic processes. The presence of two pathogenic factors prompted us to attempt to distinguish the effects triggered by mutant protein from those caused by mutant RNA in cellular models of polyglutamine diseases. We used the SLIP (Synthesis of Long Iterative Polynucleotide) method to generate plasmids expressing long CAG repeats (forming a hairpin structure), CAA interrupted CAG repeats (forming multiple unstable hairpins) or pure CAA repeats (not forming any secondary structure). We successfully modified the original SLIP protocol to generate repeats of desired length starting from constructs containing short repeat tracts. We demonstrated that the SLIP method is a time- and cost-effective approach to manipulate the lengths of expanded repeat sequences. PMID- 26270661 TI - Comparative Analysis of the Brassica napus Root and Leaf Transcript Profiling in Response to Drought Stress. AB - Drought stress is one of the major abiotic factors affecting Brassica napus (B. napus) productivity. In order to identify genes of potential importance to drought stress and obtain a deeper understanding of the molecular mechanisms regarding the responses of B. napus to dehydration stress, we performed large scale transcriptome sequencing of B. napus plants under dehydration stress using the Illumina sequencing technology. In this work, a relatively drought tolerant B. napus line, Q2, identified in our previous study, was used. Four cDNA libraries constructed from mRNAs of control and dehydration-treated root and leaf were sequenced by Illumina technology. A total of 6018 and 5377 differentially expressed genes (DEGs) were identified in root and leaf. In addition, 1745 genes exhibited a coordinated expression profile between the two tissues under drought stress, 1289 (approximately 74%) of which showed an inverse relationship, demonstrating different regulation patterns between the root and leaf. The gene ontology (GO) enrichment test indicated that up-regulated genes in root were mostly involved in "stimulus" "stress" biological process, and activated genes in leaf mainly functioned in "cell" "cell part" components. Furthermore, a comparative network related to plant hormone signal transduction and AREB/ABF, AP2/EREBP, NAC, WRKY and MYC/MYB transcription factors (TFs) provided a view of different stress tolerance mechanisms between root and leaf. Some of the DEGs identified may be candidates for future research aimed at detecting drought responsive genes and will be useful for understanding the molecular mechanisms of drought tolerance in root and leaf of B. napus. PMID- 26270664 TI - On the Optimization of a Probabilistic Data Aggregation Framework for Energy Efficiency in Wireless Sensor Networks. AB - Among the key aspects of the Internet of Things (IoT) is the integration of heterogeneous sensors in a distributed system that performs actions on the physical world based on environmental information gathered by sensors and application-related constraints and requirements. Numerous applications of Wireless Sensor Networks (WSNs) have appeared in various fields, from environmental monitoring, to tactical fields, and healthcare at home, promising to change our quality of life and facilitating the vision of sensor network enabled smart cities. Given the enormous requirements that emerge in such a setting-both in terms of data and energy-data aggregation appears as a key element in reducing the amount of traffic in wireless sensor networks and achieving energy conservation. Probabilistic frameworks have been introduced as operational efficient and performance effective solutions for data aggregation in distributed sensor networks. In this work, we introduce an overall optimization approach that improves and complements such frameworks towards identifying the optimal probability for a node to aggregate packets as well as the optimal aggregation period that a node should wait for performing aggregation, so as to minimize the overall energy consumption, while satisfying certain imposed delay constraints. Primal dual decomposition is employed to solve the corresponding optimization problem while simulation results demonstrate the operational efficiency of the proposed approach under different traffic and topology scenarios. PMID- 26270663 TI - Influence of Pre-Freezing Temperature on the Corneal Endothelial Cytocompatibility and Cell Delivery Performance of Porous Hyaluronic Acid Hydrogel Carriers. AB - The development of porous hyaluronic acid (HA) hydrogels for corneal endothelial tissue engineering is attractive because they can be used as functional cell delivery carriers to help in the reconstruction of damaged areas. The purpose of this study was to investigate the corneal endothelial cytocompatibility and cell delivery performance of porous HA hydrogel biomaterials fabricated at different pre-freezing temperatures. As compared to their counterparts prepared at -80 degrees C, the HA samples fabricated at higher pre-freezing temperature (i.e., 0 degrees C) exhibited a larger pore size and higher porosity, thereby leading to lower resistance to glucose permeation. Live/dead assays and gene expression analyses showed that the restricted porous structure of HA carriers decreases the viability and ionic pump function of cultured corneal endothelial cells (CECs). The results also indicated that the porous hydrogel biomaterials fabricated at high pre-freezing temperature seem to be more compatible with rabbit CECs. In an animal model of corneal endothelial dysfunction, the wounded rabbit corneas receiving bioengineered CEC sheets and restricted porous-structured HA carriers demonstrated poor tissue reconstruction. The therapeutic efficacy of cell sheet transplants can be improved by using carrier materials prepared at high pre freezing temperature. Our findings suggest that the cryogenic operation temperature-mediated pore microstructure of HA carriers plays an important role in corneal endothelial cytocompatibility and cell delivery performance. PMID- 26270662 TI - New Immunosuppressive Therapies in Uveitis Treatment. AB - Uveitis is an inflammatory process that initially starts in the uvea, but can also affect other adjacent eye structures, and is currently the fourth cause of blindness in developed countries. Corticoids are probably the most widespread treatment, but resorting to other immunosuppressive treatments is a frequent practice. Since the implication of different cytokines in uveitis has been well demonstrated, the majority of recent treatments for this disease include inhibitors or antibodies against these. Nevertheless, adequate treatment for each uveitis type entails a difficult therapeutic decision as no clear recommendations are found in the literature, despite the few protocolized clinical assays and many case-control studies done. This review aims to present, in order, the mechanisms and main indications of the most modern immunosuppressive drugs against cytokines. PMID- 26270665 TI - A Low-Power and Portable Biomedical Device for Respiratory Monitoring with a Stable Power Source. AB - Continuous respiratory monitoring is an important tool for clinical monitoring. Associated with the development of biomedical technology, it has become more and more important, especially in the measuring of gas flow and CO2 concentration, which can reflect the status of the patient. In this paper, a new type of biomedical device is presented, which uses low-power sensors with a piezoresistive silicon differential pressure sensor to measure gas flow and with a pyroelectric sensor to measure CO2 concentration simultaneously. For the portability of the biomedical device, the sensors and low-power measurement circuits are integrated together, and the airway tube also needs to be miniaturized. Circuits are designed to ensure the stability of the power source and to filter out the existing noise. Modulation technology is used to eliminate the fluctuations at the trough of the waveform of the CO2 concentration signal. Statistical analysis with the coefficient of variation was performed to find out the optimal driving voltage of the pressure transducer. Through targeted experiments, the biomedical device showed a high accuracy, with a measuring precision of 0.23 mmHg, and it worked continuously and stably, thus realizing the real-time monitoring of the status of patients. PMID- 26270666 TI - Study on Pyroelectric Harvesters with Various Geometry. AB - Pyroelectric harvesters convert time-dependent temperature variations into electric current. The appropriate geometry of the pyroelectric cells, coupled with the optimal period of temperature fluctuations, is key to driving the optimal load resistance, which enhances the performance of pyroelectric harvesters. The induced charge increases when the thickness of the pyroelectric cells decreases. Moreover, the induced charge is extremely reduced for the thinner pyroelectric cell when not used for the optimal period. The maximum harvested power is achieved when a 100 MUm-thick PZT (Lead zirconate titanate) cell is used to drive the optimal load resistance of about 40 MOmega. Moreover, the harvested power is greatly reduced when the working resistance diverges even slightly from the optimal load resistance. The stored voltage generated from the 75 MUm-thick PZT cell is less than that from the 400 MUm-thick PZT cell for a period longer than 64 s. Although the thinner PZT cell is advantageous in that it enhances the efficiency of the pyroelectric harvester, the much thinner 75 MUm thick PZT cell and the divergence from the optimal period further diminish the performance of the pyroelectric cell. Therefore, the designers of pyroelectric harvesters need to consider the coupling effect between the geometry of the pyroelectric cells and the optimal period of temperature fluctuations to drive the optimal load resistance. PMID- 26270667 TI - A Trajectory-Based Coverage Assessment Approach for Universal Sensor Networks. AB - To solve the problem of coverage performance assessment, this study proposes an evaluation method based on the trajectory of the target, which is applicable to universal sensor networks, including both heterogeneous and homogeneous sensor networks. Different from the traditional Voronoi algorithm, the proposed Improved Coverage Force Division (ICFD) plans a coverage force division map whichscales the qualitative coverage performancebasedon both covering intensities andlocations of the nodes. Furthermore, the Trajectory-based Evaluating Schedule (TES) is responsible for solving the quantitative coverage evaluationproblem by measuringthe resulting trajectories' Balance Values (BVs). A model of weak-point ranking conjoined in consideration of coverage force and distance can guide future deployment to compensate coverage. Comparative trials using the greedy algorithm, Voronoi algorithm, and the proposed TES verify that TES achieves the approximate results for two-stage and multistage heterogeneous sensor networks with acceptable difference and lower complexity, and it is superior to the Voronoi algorithm in homogeneous sensor networks interms of breaking the four point circle block. PMID- 26270668 TI - Comparison of Cell Disruption Methods for Improving Lipid Extraction from Thraustochytrid Strains. AB - Lipid extraction is an integral part of biodiesel production, as it facilitates the release of fatty acids from algal cells. To utilise thraustochytrids as a potential source for lipid production. We evaluated the extraction efficiency of various solvents and solvent combinations for lipid extraction from Schizochytrium sp. S31 and Thraustochytrium sp. AMCQS5-5. The maximum lipid extraction yield was 22% using a chloroform:methanol ratio of 2:1. We compared various cell disruption methods to improve lipid extraction yields, including grinding with liquid nitrogen, bead vortexing, osmotic shock, water bath, sonication and shake mill. The highest lipid extraction yields were obtained using osmotic shock and 48.7% from Schizochytrium sp. S31 and 29.1% from Thraustochytrium sp. AMCQS5-5. Saturated and monounsaturated fatty acid contents were more than 60% in Schizochytrium sp. S31 which suggests their suitability for biodiesel production. PMID- 26270669 TI - Climate Change and Health on the U.S. Gulf Coast: Public Health Adaptation is Needed to Address Future Risks. AB - The impacts of climate change on human health have been documented globally and in the United States. Numerous studies project greater morbidity and mortality as a result of extreme weather events and other climate-sensitive hazards. Public health impacts on the U.S. Gulf Coast may be severe as the region is expected to experience increases in extreme temperatures, sea level rise, and possibly fewer but more intense hurricanes. Through myriad pathways, climate change is likely to make the Gulf Coast less hospitable and more dangerous for its residents, and may prompt substantial migration from and into the region. Public health impacts may be further exacerbated by the concentration of people and infrastructure, as well as the region's coastal geography. Vulnerable populations, including the very young, elderly, and socioeconomically disadvantaged may face particularly high threats to their health and well-being. This paper provides an overview of potential public health impacts of climate variability and change on the Gulf Coast, with a focus on the region's unique vulnerabilities, and outlines recommendations for improving the region's ability to minimize the impacts of climate-sensitive hazards. Public health adaptation aimed at improving individual, public health system, and infrastructure resilience is urgently needed to meet the challenges climate change may pose to the Gulf Coast in the coming decades. PMID- 26270670 TI - Factors Contributing to Hypoxia in the Minjiang River Estuary, Southeast China. AB - Dissolved oxygen (DO) is not only a fundamental parameter of coastal water quality, but also an indication of organics decomposed in water and their degree of eutrophication. There has been a concern about the deterioration of dissolved oxygen conditions in the Minjiang River Estuary, the longest river in Fujian Province, Southeast China. In this study, the syntheses effects on DO was analyzed by using a four year time series of DO concentration and ancillary parameters (river discharge, water level, and temperature) from the Fuzhou Research Academy of Environmental Sciences, at three automated stations along the Minjiang River Estuary. Hypoxia occurred exclusively in the fluvial sections of the estuary during the high temperature and low river discharge period and was remarkably more serious in the river reach near the large urban area of Fuzhou. Enhancement of respiration by temperature and discharge of domestic sewage and industrial wastewater, versus regeneration of waters and dilution of pollutant concentration with increased river discharge, which regarded as the dominant antagonist processes that controlled the appearance of seasonal hypoxia. During the high temperature and the drought period, minimal mainstream flow above 700 m(3)?s(-1), reduction of pollutants and forbidding sediment dredging in the South Channel should be guaranteed for strong supports on water quality management and drinking water source protection. PMID- 26270671 TI - Evidence of Coal-Fly-Ash Toxic Chemical Geoengineering in the Troposphere: Consequences for Public Health. AB - The widespread, intentional and increasingly frequent chemical emplacement in the troposphere has gone unidentified and unremarked in the scientific literature for years. The author presents evidence that toxic coal combustion fly ash is the most likely aerosolized particulate sprayed by tanker-jets for geoengineering, weather-modification and climate-modification purposes and describes some of the multifold consequences on public health. Two methods are employed: (1) Comparison of 8 elements analyzed in rainwater, leached from aerosolized particulates, with corresponding elements leached into water from coal fly ash in published laboratory experiments, and (2) Comparison of 14 elements analyzed in dust collected outdoors on a high-efficiency particulate air (HEPA) filter with corresponding elements analyzed in un-leached coal fly ash material. The results show: (1) the assemblage of elements in rainwater and in the corresponding experimental leachate are essentially identical. At a 99% confidence interval, they have identical means (T-test) and identical variances (F-test); and (2) the assemblage of elements in the HEPA dust and in the corresponding average un leached coal fly ash are likewise essentially identical. The consequences on public health are profound, including exposure to a variety of toxic heavy metals, radioactive elements, and neurologically-implicated chemically mobile aluminum released by body moisture in situ after inhalation or through transdermal induction. PMID- 26270672 TI - Model Averaging for Improving Inference from Causal Diagrams. AB - Model selection is an integral, yet contentious, component of epidemiologic research. Unfortunately, there remains no consensus on how to identify a single, best model among multiple candidate models. Researchers may be prone to selecting the model that best supports their a priori, preferred result; a phenomenon referred to as "wish bias". Directed acyclic graphs (DAGs), based on background causal and substantive knowledge, are a useful tool for specifying a subset of adjustment variables to obtain a causal effect estimate. In many cases, however, a DAG will support multiple, sufficient or minimally-sufficient adjustment sets. Even though all of these may theoretically produce unbiased effect estimates they may, in practice, yield somewhat distinct values, and the need to select between these models once again makes the research enterprise vulnerable to wish bias. In this work, we suggest combining adjustment sets with model averaging techniques to obtain causal estimates based on multiple, theoretically-unbiased models. We use three techniques for averaging the results among multiple candidate models: information criteria weighting, inverse variance weighting, and bootstrapping. We illustrate these approaches with an example from the Pregnancy, Infection, and Nutrition (PIN) study. We show that each averaging technique returns similar, model averaged causal estimates. An a priori strategy of model averaging provides a means of integrating uncertainty in selection among candidate, causal models, while also avoiding the temptation to report the most attractive estimate from a suite of equally valid alternatives. PMID- 26270674 TI - Validity of Two New Brief Instruments to Estimate Vegetable Intake in Adults. AB - Cost effective population-based monitoring tools are needed for nutritional surveillance and interventions. The aim was to evaluate the relative validity of two new brief instruments (three item: VEG3 and five item: VEG5) for estimating usual total vegetable intake in comparison to a 7-day dietary record (7DDR). Sixty-four Australian adult volunteers aged 30 to 69 years (30 males, mean age +/ SD 56.3 +/- 9.2 years and 34 female mean age +/- SD 55.3 +/- 10.0 years). Pearson correlations between 7DDR and VEG3 and VEG5 were modest, at 0.50 and 0.56, respectively. VEG3 significantly (p < 0.001) underestimated mean vegetable intake compared to 7DDR measures (2.9 +/- 1.3 vs. 3.6 +/- 1.6 serves/day, respectively), whereas mean vegetable intake assessed by VEG5 did not differ from 7DDR measures (3.3 +/- 1.5 vs. 3.6 +/- 1.6 serves/day). VEG5 was also able to correctly identify 95%, 88% and 75% of those subjects not consuming five, four and three serves/day of vegetables according to their 7DDR classification. VEG5, but not VEG3, can estimate usual total vegetable intake of population groups and had superior performance to VEG3 in identifying those not meeting different levels of vegetable intake. VEG5, a brief instrument, shows measurement characteristics useful for population-based monitoring and intervention targeting. PMID- 26270675 TI - Beverage Consumption: Are Alcoholic and Sugary Drinks Tipping the Balance towards Overweight and Obesity? AB - The role that energy-containing beverages may play in the development of overweight and obesity remains highly controversial, in particular the alcoholic and sugar-sweetened beverages (SSB). Both of these beverage formats have been increasing as a percentage of the westernized diet over the past 20 years, and both have contributed significantly to an increase in energy consumed in liquid form. Data from epidemiology and intervention studies however have long been contradictory, despite mechanistic evidence pointing towards poor compensation for addition of "liquid" energy from these two sources into the diet providing a strong rational for the balance to be tipped towards weight gain. Regulatory and government intervention has been increasing globally, particularly with respect to intake of SSBs in children. This narrative review presents evidence which both supports and refutes the link between alcohol and carbohydrate-containing liquids and the regulation of body weight, and investigates mechanisms which may underpin any relationship between increased beverage consumption and increased energy intake, body weight and adiposity. PMID- 26270673 TI - The Interaction between Cyclin B1 and Cytomegalovirus Protein Kinase pUL97 is Determined by an Active Kinase Domain. AB - Replication of human cytomegalovirus (HCMV) is characterized by a tight virus host cell interaction. Cyclin-dependent protein kinases (CDKs) are functionally integrated into viral gene expression and protein modification. The HCMV-encoded protein kinase pUL97 acts as a CDK ortholog showing structural and functional similarities. Recently, we reported an interaction between pUL97 kinase with a subset of host cyclins, in particular with cyclin T1. Here, we describe an interaction of pUL97 at an even higher affinity with cyclin B1. As a striking feature, the interaction between pUL97 and cyclin B1 proved to be strictly dependent on pUL97 activity, as interaction could be abrogated by treatment with pUL97 inhibitors or by inserting mutations into the conserved kinase domain or the nonconserved C-terminus of pUL97, both producing loss of activity. Thus, we postulate that the mechanism of pUL97-cyclin B1 interaction is determined by an active pUL97 kinase domain. PMID- 26270676 TI - Hedgehog Signaling in the Maintenance of Cancer Stem Cells. AB - Cancer stem cells (CSCs) represent a rare population of cells with the capacity to self-renew and give rise to heterogeneous cell lineages within a tumour. Whilst the mechanisms underlying the regulation of CSCs are poorly defined, key developmental signaling pathways required for normal stem and progenitor functions have been strongly implicated. Hedgehog (Hh) signaling is an evolutionarily-conserved pathway essential for self-renewal and cell fate determination. Aberrant Hh signaling is associated with the development and progression of various types of cancer and is implicated in multiple aspects of tumourigenesis, including the maintenance of CSCs. Here, we discuss the mounting evidence suggestive of Hh-driven CSCs in the context of haematological malignancies and solid tumours and the novel strategies that hold the potential to block many aspects of the transformation attributed to the CSC phenotype, including chemotherapeutic resistance, relapse and metastasis. PMID- 26270678 TI - Challenges in Antibody Development against Tn and Sialyl-Tn Antigens. AB - The carbohydrate antigens Tn and sialyl-Tn (STn) are expressed in most carcinomas and usually absent in healthy tissues. These antigens have been correlated with cancer progression and poor prognosis, and associated with immunosuppressive microenvironment. Presently they are used in clinical trials as therapeutic vaccination, but with limited success due to their low immunogenicity. Alternatively, anti-Tn and/or STn antibodies may be used to harness the immune system against tumor cells. Whilst the development of antibodies against these antigens had a boost two decades ago for diagnostic use, so far no such antibody entered into clinical trials. Possible limitations are the low specificity and efficiency of existing antibodies and that novel antibodies are still necessary. The vast array of methodologies available today will allow rapid antibody development and novel formats. Following the advent of hybridoma technology, the immortalization of human B cells became a methodology to obtain human monoclonal antibodies with better specificity. Advances in molecular biology including phage display technology for high throughput screening, transgenic mice and more recently molecularly engineered antibodies enhanced the field of antibody production. The development of novel antibodies against Tn and STn taking advantage of innovative technologies and engineering techniques may result in innovative therapeutic antibodies for cancer treatment. PMID- 26270681 TI - Editorial commentary: treatment of asymptomatic bacteriuria might be harmful. PMID- 26270677 TI - Bacterial Genotoxins: Merging the DNA Damage Response into Infection Biology. AB - Bacterial genotoxins are unique among bacterial toxins as their molecular target is DNA. The consequence of intoxication or infection is induction of DNA breaks that, if not properly repaired, results in irreversible cell cycle arrest (senescence) or death of the target cells. At present, only three bacterial genotoxins have been identified. Two are protein toxins: the cytolethal distending toxin (CDT) family produced by a number of Gram-negative bacteria and the typhoid toxin produced by Salmonella enterica serovar Typhi. The third member, colibactin, is a peptide-polyketide genotoxin, produced by strains belonging to the phylogenetic group B2 of Escherichia coli. This review will present the cellular effects of acute and chronic intoxication or infection with the genotoxins-producing bacteria. The carcinogenic properties and the role of these effectors in the context of the host-microbe interaction will be discussed. We will further highlight the open questions that remain to be solved regarding the biology of this unusual family of bacterial toxins. PMID- 26270682 TI - Access to Costly New Hepatitis C Drugs: Medicine, Money, and Advocacy. AB - Hepatitis C affects >3 million people in the United States, and often leads to end-stage liver disease or death. In 2014, several new drugs to treat hepatitic C virus received US Food and Drug Administration approval, with remarkable cure rates exceeding 90%. Medicaid, however, is rationing these drugs, and other insurers have restricted coverage due to their exorbitant costs and the large size of the population in need. These access barriers and disparities have resulted in national patient advocacy mobilization, US congressional inquiry, and legal challenges. The US Department of Health and Human Services has been urged to intervene. We propose the establishment of a federal program, analogous to AIDS Drug Assistance Programs, to reduce access barriers and facilitate focused price negotiations. The federal government may further undertake a nonvoluntary acquisition of the pharmaceutical patents pursuant to federal statutory authority and principles of eminent domain. Projections indicate this proposal could lower costs by 90% and eliminate rationing. PMID- 26270680 TI - Changing Trends in Complications and Mortality Rates Among US Youth and Young Adults With HIV Infection in the Era of Combination Antiretroviral Therapy. AB - BACKGROUND: Combination antiretroviral therapy (cART) has resulted in a dramatic decrease in human immunodeficiency virus (HIV)-related opportunistic infections and deaths in US youth, but both continue to occur. METHODS: We estimated the incidence of complications and deaths in IMPAACT P1074, a long-term US-based prospective multicenter cohort study conducted from April 2008 to June 2014. Incidence rates of selected diagnoses and trends over time were compared with those from a previous observational cohort study, P219C (2004-2007). Causes of death and relevant demographic and clinical features were reviewed. RESULTS: Among 1201 HIV-infected youth in P1074 (87% perinatally infected; mean [standard deviation] age at last chart review, 20.9 [5.4] years), psychiatric and neurodevelopmental disorders, asthma, pneumonia, and genital tract infections were among the most common comorbid conditions. Compared with findings in P219C, conditions with significantly increased incidence included substance or alcohol abuse, latent tuberculosis, diabetes mellitus, atypical mycobacterial infections, vitamin D deficiency or metabolic bone disorders, anxiety disorders, and fractures; the incidence of pneumonia decreased significantly. Twenty-eight deaths occurred, yielding a standardized mortality rate 31.5 times that of the US population. Those who died were older, less likely to be receiving cART, and had lower CD4 cell counts and higher viral loads. Most deaths (86%) were due to HIV related medical conditions. CONCLUSIONS: Opportunistic infections and deaths are less common among HIV-infected youth in the US in the cART era, but the mortality rate remains elevated. Deaths were associated with poor HIV control and older age. Emerging complications, such as psychiatric, inflammatory, metabolic, and genital tract diseases, need to be addressed. PMID- 26270685 TI - "Lyme": Chronic Fatigue Syndrome by Another Name? PMID- 26270684 TI - Asymptomatic bacteriuria treatment is associated with a higher prevalence of antibiotic resistant strains in women with urinary tract infections. AB - BACKGROUND: Women suffering from recurrent urinary tract infections (rUTIs) are routinely treated for asymptomatic bacteriuria (AB), but the consequences of this procedure on antibiotic resistance are not fully known. The aim of this study was to evaluate the impact of AB treatment on antibiotic resistance among women with rUTIs. METHODS: The study population consisted of 2 groups of women who had previously been enrolled in a randomized clinical trial: group A was not treated, and group B was treated. All women were scheduled for follow-up visits every 6 months, or more frequently if symptoms arose. Microbiological evaluation was performed only in symptomatic women. All women were followed up for a mean of 38.8 months to analyze data from urine cultures and antibiograms. RESULTS: The previous study population consisted of 673 women, but 123 did not attend the entire follow-up period. For the final analysis, 257 of the remaining 550 patients were assigned to group A, and 293 to group B. At the end of follow-up, the difference in recurrence rates was statistically significant (P < .001): 97 (37.7%) in group A versus 204 (69.6%) in group B. Isolated Escherichia coli from group B showed higher resistance to amoxicillin-clavulanic acid (P = .03), trimethoprim-sulfamethoxazole (P = .01), and ciprofloxacin (P = .03) than that from group A. CONCLUSIONS: This study shows that AB treatment is associated with a higher occurrence of antibiotic-resistant bacteria, indicating that AB treatment in women with rUTIs is potentially dangerous. PMID- 26270679 TI - Chemical Library Screening and Structure-Function Relationship Studies Identify Bisacodyl as a Potent and Selective Cytotoxic Agent Towards Quiescent Human Glioblastoma Tumor Stem-Like Cells. AB - Cancer stem-like cells reside in hypoxic and slightly acidic tumor niches. Such microenvironments favor more aggressive undifferentiated phenotypes and a slow growing "quiescent state" which preserves them from chemotherapeutic agents that essentially target proliferating cells. Our objective was to identify compounds active on glioblastoma stem-like cells, including under conditions that mimick those found in vivo within this most severe and incurable form of brain malignancy. We screened the Prestwick Library to identify cytotoxic compounds towards glioblastoma stem-like cells, either in a proliferating state or in more slow-growing "quiescent" phenotype resulting from non-renewal of the culture medium in vitro. Compound effects were assessed by ATP-level determination using a cell-based assay. Twenty active molecules belonging to different pharmacological classes have thus been identified. Among those, the stimulant laxative drug bisacodyl was the sole to inhibit in a potent and specific manner the survival of quiescent glioblastoma stem-like cells. Subsequent structure function relationship studies led to identification of 4,4'-dihydroxydiphenyl-2 pyridyl-methane (DDPM), the deacetylated form of bisacodyl, as the pharmacophore. To our knowledge, bisacodyl is currently the only known compound targeting glioblastoma cancer stem-like cells in their quiescent, more resistant state. Due to its known non-toxicity in humans, bisacodyl appears as a new potential anti tumor agent that may, in association with classical chemotherapeutic compounds, participate in tumor eradication. PMID- 26270686 TI - A randomized, placebo-controlled trial of preemptive antifungal therapy for the prevention of invasive candidiasis following gastrointestinal surgery for intra abdominal infections. AB - BACKGROUND: Patients undergoing emergency gastrointestinal surgery for intra abdominal infection are at risk of invasive candidiasis (IC) and candidates for preemptive antifungal therapy. METHODS: This exploratory, randomized, double blind, placebo-controlled trial assessed a preemptive antifungal approach with micafungin (100 mg/d) in intensive care unit patients requiring surgery for intra abdominal infection. Coprimary efficacy variables were the incidence of IC and the time from baseline to first IC in the full analysis set; an independent data review board confirmed IC. An exploratory biomarker analysis was performed using logistic regression. RESULTS: The full analysis set comprised 124 placebo- and 117 micafungin-treated patients. The incidence of IC was 8.9% for placebo and 11.1% for micafungin (difference, 2.24%; [95% confidence interval, -5.52 to 10.20]). There was no difference between the arms in median time to IC. The estimated odds ratio showed that patients with a positive (1,3)-beta-d-glucan (betaDG) result were 3.66 (95% confidence interval, 1.01-13.29) times more likely to have confirmed IC than those with a negative result. CONCLUSIONS: This study was unable to provide evidence that preemptive administration of an echinocandin was effective in preventing IC in high-risk surgical intensive care unit patients with intra-abdominal infections. This may have been because the drug was administered too late to prevent IC coupled with an overall low number of IC events. It does provide some support for using betaDG to identify patients at high risk of IC. CLINICAL TRIALS REGISTRATION: NCT01122368. PMID- 26270683 TI - Emerging and Underrecognized Complications of Illicit Drug Use. AB - Illicit drug use can result in a wide range of medical complications. As the availability, synthesis, and popularity of illicit drugs evolve over time, new syndromes associated with their use may mimic infections. Some of these symptoms are anticipated drug effects, and others are complications of adulterants mixed with drugs or complications from the method of using drugs. Some illicit drugs are associated with rare infections, which are difficult to diagnosis with standard microbiological techniques. The goal of this review is to orient a wide range of clinicians-including general practitioners, emergency medicine providers, and infectious diseases specialists-to complications of illicit drug use that may be underrecognized. Improving awareness of infectious and noninfectious complications of illicit drug can expedite diagnosis and medical treatment of persons who use drugs and facilitate targeted harm reduction counseling to prevent future complications. PMID- 26270687 TI - Cell-Associated HIV-1 DNA and RNA Decay Dynamics During Early Combination Antiretroviral Therapy in HIV-1-Infected Infants. AB - BACKGROUND: The decay of human immunodeficiency virus type 1 (HIV-1)-infected cells during early combination antiretroviral therapy (cART) in infected infants is not defined. METHODS: HIV-1 DNA, including 2-long terminal repeat (2-LTR) circles, and multiply spliced (ms-) and unspliced (us-) HIV-1 RNA concentrations were measured at 0, 24, 48, and 96 weeks of cART in infants from the IMPAACT P1030 trial receiving lopinavir-ritonavir-based cART. The ratio of HIV-1 DNA concentrations to replication-competent genomes was also estimated. Linear mixed effects models with random intercept and linear splines were used to estimate patient-specific decay kinetics of HIV-1 DNA. RESULTS: The median HIV-1 DNA concentration before cART at a median age of 2 months was 3.2 log10 copies per million PBMC. With cART, the average estimated patient-specific change in HIV-1 DNA concentrations was -0.040 log10/week (95% confidence interval [CI], -.05, .03) between 0 and 24 weeks and -0.017 log10/week between 24 and 48 weeks (95% CI, -.024, -.01). 2-LTR circles decreased with cART but remained detectable through 96 weeks. Pre-cART HIV-1 DNA concentration was correlated with time to undetectable plasma viral load and post-cART HIV-1 DNA at 96 weeks; although HIV 1 DNA concentrations exceeded replication-competent HIV-1 genomes by 148-fold. Almost all infants had ms- and usRNA detected pre-cART, with 75% having usRNA through 96 weeks of cART. CONCLUSIONS: By 2 months of age, a large pool of HIV-1 infected cells is established in perinatal infection, which influences time to undetectable viral load and reservoir size. This has implications for informing novel approaches aimed at early restriction of HIV-1 reservoirs to enable virologic remission and cure. PMID- 26270688 TI - Editorial Commentary: Scaling Up Antiretroviral Preexposure Prophylaxis: Moving From Trials to Implementation. PMID- 26270689 TI - Study design questions regarding long-term assessment of health-related quality of life in patients with culture-confirmed early Lyme disease. PMID- 26270690 TI - Reply to Greenberg. PMID- 26270692 TI - Effects of a Body-Weight Supporting Kite on Sprint Running Kinematics in Well Trained Sprinters. AB - Data of elite sprinters indicate that faster athletes realize shorter ground contact times compared with slower individuals. Furthermore, the importance of the so-called "front side mechanics" for elite sprint performance is frequently emphasized by researchers and coaches. Recently, it was demonstrated that using a body-weight supporting kite during full-effort sprints in highly trained sprinters leads to a reduction in ground contact time. The aim of this study was to investigate possible negative effects of this body-weight supporting device on sprint running kinematics, which was not clarified in previous studies. Eleven well-trained Austrian sprinters performed flying 20-m sprints under 2 conditions: (a) free sprint (FS); and (b) body-weight supported sprint (BWS). Sprint cycle characteristics were recorded during the high-speed phase by a 16 camera 3D system (Vicon), an optical acquisition system (Optojump-next), and a high-speed camera. Paired sample t-tests and Cohen's d effect size were used to determine differences between sprinting conditions. Compared with FS, BWS caused a decrease in ground contact time by 5.6% and an increase in air time by 5.5% (both p < 0.001), whereas stride length and rate remained unchanged. Furthermore, a reduced hip joint extension at and after take-off, an increased maximal hip joint flexion (i.e., high knee position), and a smaller horizontal distance of the touchdown to the center of gravity could be observed (all p < 0.01). These results indicate no negative effects on front side mechanics during BWS and that sprinting with a body-weight supporting kite seems to be a highly specific method to reduce ground contact time in well-trained sprinters. PMID- 26270693 TI - Physiological Effects of Nucleotide Supplementation on Resistance Exercise Stress in Men and Women. AB - Nucleotide supplementation can reduce postexercise immunosuppression and hypothalamic-pituitary axis (HPA) axis activation in endurance exercise models. Nucleotide supplementation may aid recovery from other exercise modalities, such as heavy resistance exercise. Thus, the purpose of this investigation was to investigate the effects of nucleotide supplementation on the acute cortisol and immune responses to heavy resistance exercise and its effects on recovery. A double-blinded, crossover, mixed methods design with 10 men and 10 women was used. Each performed an acute heavy resistance exercise protocol (AHREP) after a loading period with a nucleotide or placebo supplement. Before and after the AHREP, and at 24, 48, and 72 hours post, blood samples were analyzed for cortisol, myeloperoxidase (MPO), and absolute neutrophil, lymphocyte, and monocyte counts. Creatine kinase (CK) was analyzed before and 24, 48, and 72 hours after the AHREP. Performance measures, including peak back squat isometric force and peak countermovement jump power were also analyzed. Nucleotide supplementation resulted in significant (p <= 0.05) decreases in cortisol and MPO immediately after the AHREP, and significantly lower CK values 24 hours later. The AHREP significantly affected leukocyte counts; however, no treatment effects were observed. Greater isometric force was observed immediately after AHREP and at 24 hours and 48 hours with nucleotide supplementation. Nucleotide supplementation seems to attenuate muscle damage, HPA axis and immune system activation, and performance decrements after heavy resistance exercise. PMID- 26270691 TI - Applying a PrEP Continuum of Care for Men Who Have Sex With Men in Atlanta, Georgia. AB - Reductions in human immunodeficiency virus (HIV) incidence with pre-exposure prophylaxis (PrEP) for men who have sex with men (MSM) will require significant coverage of those at risk. We propose a simplified framework, similar to the HIV care continuum, to achieve protection with PrEP as follows: 1. At-risk MSM; 2. Awareness of and willingness to take PrEP; 3. Access to healthcare; 4. Receiving a prescription; and 5. Adhering to effective PrEP. We evaluated the PrEP care continuum on an Atlanta cohort of MSM and projected how many MSM might achieve protection from HIV. Even with optimistic estimates, few Atlanta MSM (15%) are projected to achieve protection from HIV with PrEP given the significant barriers described. Each continuum step represents an important point for intervention that could substantially increase the overall effectiveness of PrEP. In addition, novel strategies for PrEP delivery are needed to achieve the necessary effectiveness for Atlanta MSM at risk of HIV. PMID- 26270694 TI - Electromyographical and Perceptual Responses to Different Resistance Intensities in a Squat Protocol: Does Performing Sets to Failure With Light Loads Produce the Same Activity? AB - This investigation examined peak motor unit activity during sets that differed in resistance (50, 70, or 90% 1 repetition maximum [1RM]). Ten resistance-trained men (age, 23 +/- 3 years; height, 187 +/- 7 cm; body mass, 91.5 +/- 6.9 kg; squat 1RM, 141 +/- 28 kg) were assessed by electromyography (EMG) on the vastus lateralis and vastus medialis muscles in a randomized within-subject experiment consisting of 2 test visits: a drop-set day and a single-set day using only the 50% of 1RM intensity performed to failure. At the start of each day, subjects performed 2 submaximal repetition sets (50% 1RM * 10 repetitions and 70% 1RM * 7 repetitions). On the drop-set day, subjects performed 3 consecutive maximal repetition sets at 90%, 70%, and 50% 1RM to failure with no rest periods in between. On the single-set day, subjects performed a maximal repetition set at 50% 1RM to failure. Overall, the maximal repetition sets to failure at 50% and 70% 1RM resulted in higher peak EMG amplitude than during submaximal repetition sets with the same resistance. However, peak EMG amplitude was significantly (p <= 0.05) greater in the maximal 90% 1RM set than all other sets performed. When sets were performed to failure, ratings of perceived exertion (CR-10) did not differ over the intensity range of loads and suggests that perception is not capable of accurately detecting the actual amount of motor unit activation. The results of this investigation indicate that using higher external resistance is a more effective means of increasing motor unit activity than increasing the number of repetitions performed with lighter weights even when the end point is muscular failure. Accordingly, previous recommendations for the use of heavier loads during resistance training programs to stimulate the maximal development of strength and hypertrophy are further supported. PMID- 26270695 TI - The Effects of Forced Exhalation and Inhalation, Grunting, and Valsalva Maneuver on Forehand Force in Collegiate Tennis Players. AB - To examine the effects of forced expiration (FE), forced inspiration (FI), grunting (GR), and valsalva maneuver (VM), on air volume, maximum force production, and muscle recruitment during a simulated forehand stroke in collegiate tennis players. Superficial electrodes were placed over the anterior deltoid, pectoralis major, rectus abdominis, lumbar and thoracic erector spinae, and external and internal obliques. Subjects stood in a simulated forehand stroke stance with their dominant hand positioned on a force plate. Subjects performed 3 repetitions of maximal 2- to 3-second isometric forehands with randomly assigned breathing conditions (FE, FI, VM, and GR) and 30-seconds rest between contractions. Air volumes were also collected during each trial. A repeated measures multivariate analysis of variance compared normalized peak electromyographic activity across the 7 muscle groups. Separate repeated measures ANOVAs compared the effect of breathing conditions on peak force production and air volume. Statistical significance was set at p <= 0.05 for all analyses. Overall muscle activity differed significantly by breathing condition (p = 0.031) with greater anterior deltoid activity was seen in FE and GR vs. VM. Internal oblique activity was significantly greater in GR than FI or VM, and thoracic erector spinae activity was significantly greater during FE and VM than FI. Force production did not differ significantly among breathing conditions (p = 0.74); however, GR forces were greater than FI and VM forces (p <= 0.05). Forced expiration air volume was significantly greater (p < 0.001) than FI, GR, or VM. These findings suggest that either GR or a more quiescent FE can be used to enhance force production. Forced expiration is a potentially safer alternative to VM and more aurally pleasing than GR. PMID- 26270697 TI - Emergence of Coherence through Variation of Intermolecular Distances in a Series of Molecular Dimers. AB - Quantum coherences between electronically excited molecules are a signature of entanglement and play an important role for energy transport in molecular assemblies. Here we monitor and analyze for a homologous series of molecular dimers embedded in a solid host the emergence of coherence with decreasing intermolecular distance by single-molecule spectroscopy and quantum chemistry. Coherent signatures appear as an enhancement of the purely electronic transitions in the dimers which is reflected by changes of fluorescence spectra and lifetimes. Effects that destroy the coherence are the coupling to the surroundings and to vibrational excitations. Complementary information is provided by excitation spectra from which the electronic coupling strengths were extracted and found to be in good agreement with calculated values. By revealing various signatures of intermolecular coherence, our results pave the way for the rational design of molecular systems with entangled states. PMID- 26270696 TI - The Synthesis of Stable, Complex Organocesium Tetramic Acids through the Ugi Reaction and Cesium-Carbonate-Promoted Cascades. AB - Two structurally unique organocesium carbanionic tetramic acids have been synthesized through expeditious and novel cascade reactions of strategically functionalized Ugi skeletons delivering products with two points of potential diversification. This is the first report of the use of multicomponent reactions and subsequent cascades to access complex, unprecedented organocesium architectures. Moreover, this article also highlights the first use of mild cesium carbonate as a cesium source for the construction of cesium organometallic scaffolds. Relativistic DFT calculations provide an insight into the electronic structure of the reported compounds. PMID- 26270698 TI - Self-Assembled Two-Dimensional Heteromolecular Nanoporous Molecular Arrays on Epitaxial Graphene. AB - The development of graphene functionalization strategies that simultaneously achieve two-dimensional (2D) spatial periodicity and substrate registry is of critical importance for graphene-based nanoelectronics and related technologies. Here, we demonstrate the generation of a hydrogen-bonded molecularly thin organic heteromolecular nanoporous network on epitaxial graphene on SiC(0001) using room temperature ultrahigh vacuum scanning tunneling microscopy. In particular, perylenetetracarboxylic diimide (PTCDI) and melamine are intermixed to form a spatially periodic 2D nanoporous network architecture with hexagonal symmetry and a lattice parameter of 3.45 +/- 0.10 nm. The resulting adlayer is in registry with the underlying graphene substrate and possesses a characteristic domain size of 40-50 nm. This molecularly defined nanoporous network holds promise as a template for 2D ordered chemical modification of graphene at lengths scales relevant for graphene band structure engineering. PMID- 26270699 TI - Accurate Calculations of Rotationally Inelastic Scattering Cross Sections Using Mixed Quantum/Classical Theory. AB - For computational treatment of rotationally inelastic scattering of molecules, we propose to use the mixed quantum/classical theory, MQCT. The old idea of treating translational motion classically, while quantum mechanics is used for rotational degrees of freedom, is developed to the new level and is applied to Na + N2 collisions in a broad range of energies. Comparison with full-quantum calculations shows that MQCT accurately reproduces all, even minor, features of energy dependence of cross sections, except scattering resonances at very low energies. The remarkable success of MQCT opens up wide opportunities for computational predictions of inelastic scattering cross sections at higher temperatures and/or for polyatomic molecules and heavier quenchers, which is computationally close to impossible within the full-quantum framework. PMID- 26270700 TI - The Raman Spectrum of the CH3NH3PbI3 Hybrid Perovskite: Interplay of Theory and Experiment. AB - We report the low-frequency resonant Raman spectrum of methylammonium lead iodide, a prototypical perovskite for solar cells applications, on mesoporous Al2O3. The measured spectrum assignment is assisted by DFT simulations of the Raman spectra of suitable periodic and model systems. The bands at 62 and 94 cm( 1) are assigned respectively to the bending and to the stretching of the Pb-I bonds, and are thus diagnostic modes of the inorganic cage. We also assign the librations of the organic cations at 119 and 154 cm(-1). The broad, unstructured 200-400 cm(-1) features are assigned to the torsional mode of the methylammonium cations, which we propose as a marker of the orientational disorder of the material. Our study provides the basis to interpret the Raman spectra of organohalide perovskites, which may allow one to further understand the properties of this important class of materials in relation to their full exploitation in solar cells. PMID- 26270702 TI - Computational Design of Core/Shell Nanoparticles for Oxygen Reduction Reactions. AB - A computational strategy to design core/shell nanoparticle catalysts for oxygen reduction reactions (ORRs) is proposed based on multiscale modeling. Using a quantum mechanics/molecular mechanics (QM/MM) coupling method, we have studied the ORR on Pt-Cu core/shell nanoparticles with the size ranging from 3 to 8 nm. We have calculated the oxygen adsorption energy on the nanoparticle surface (a descriptor for ORR activity) as a function of the nanoparticle size and thickness of the Pt shell. We find that the Pt-Cu core/shell nanoparticles exhibit higher ORR activities than flat Pt(111) surfaces, consistent with experimental observations. We predict that the diameter of the core/shell nanoparticles should be larger than 7 nm to reach the peak of ORR activities. By examining the effects of ligand, quantum confinement, and surface strain, we confirm that the strain plays the dominant role on ORR activities for the core/shell nanoparticles. A universal relation between the surface strain and the oxygen adsorption energy is established based on which one can computationally screen and design core/shell nanoparticle catalysts for superior ORR activities. PMID- 26270701 TI - Tunable Electronic Properties of Two-Dimensional Transition Metal Dichalcogenide Alloys: A First-Principles Prediction. AB - We investigated the composition-dependent electronic properties of two dimensional transition-metal dichalcogenide alloys (WxMo1-xS2) based on first principles calculations by applying the supercell method and effective band structure approximation. It was found that hole effective mass decreases linearly with increasing W composition, and electron effective mass of alloys is always larger than that of their binary constituents. The different behaviors of electrons and holes in alloys are attributed to the fact that metal d-orbitals have different contributions to conduction bands of MoS2 and WS2 but almost identical contributions to valence bands. We examined the conduction polarity of WxMo1-xS2 monolayer alloys with four metal electrode materials (Au, Ag, Cu, and Pd). It suggests the main carrier type for transport in transistors could change from electrons to holes as W composition increases if high work function metal contacts were used. The tunable electronic properties of two-dimensional transition-metal dichalcogenide alloys make them attractive for electronic and optoelectronic applications. PMID- 26270703 TI - Interface Limited Lithium Transport in Solid-State Batteries. AB - Understanding the role of interfaces is important for improving the performance of all-solid-state lithium ion batteries. To study these interfaces, we present a novel approach for fabrication of electrochemically active nanobatteries using focused ion beams and their characterization by analytical electron microscopy. Morphological changes by scanning transmission electron microscopy imaging and correlated elemental concentration changes by electron energy loss spectroscopy mapping are presented. We provide first evidence of lithium accumulation at the anode/current collector (Si/Cu) and cathode/electrolyte (LixCoO2/LiPON) interfaces, which can be accounted for the irreversible capacity losses. Interdiffusion of elements at the Si/LiPON interface was also witnessed with a distinct contrast layer. These results highlight that the interfaces may limit the lithium transport significantly in solid-state batteries. Fabrication of electrochemically active nanobatteries also enables in situ electron microscopy observation of electrochemical phenomena in a variety of solid-state battery chemistries. PMID- 26270705 TI - A Fresh Look at Resonances and Complex Absorbing Potentials: Density Matrix-Based Approach. AB - A new strategy of using complex absorbing potentials (CAPs) within electronic structure calculations of metastable electronic states, which are ubiquitous in chemistry and physics, is presented. The stumbling block in numerical applications of CAPs is the necessity to optimize the CAP strength for each system, state, and one-electron basis set, while there is no clear metric to assess the quality of the results and no simple algorithm of achieving numerical convergence. By analyzing the behavior of resonance wave functions, we found that robust results can be obtained when considering fully stabilized resonance states characterized by constant density at large eta (parameter determining the CAP strength). Then the perturbation due to the finite-strength CAP can be removed by a simple energy correction derived from energy decomposition analysis and response theory. The utility of this approach is illustrated by CAP-augmented calculations of several shape resonances using EOM-EA-CCSD with standard Gaussian basis sets. PMID- 26270706 TI - Circularly Polarized Luminescence in Chiral Aggregates: Dependence of Morphology on Luminescence Dissymmetry. AB - The self-assembly of a chiral perylene bisimide bichromophoric derivative possessing a 1,1'-binaphthalene bridge was investigated by adopting two different methodologies, leading to the formation of aggregates with dissimilar morphologies. The chiral nature of the aggregated structures was optically probed with the help of circular dichroism (CD), vibrational circular dichroism (VCD), and circularly polarized luminescence (CPL). The one-dimensional aggregates formed in methylcyclohexane (MCH) exhibited twice the value of luminescence dissymmetry factor (glum) when compared with the spherical aggregates formed in chloroform at higher concentration. The summation of excitonic couplings between the individual chromophoric units in an aggregated system is responsible for the remarkably high luminescence dissymmetry exhibited by the chiral aggregates. The nanostructures could be successfully embedded into polymer films, leading to the fabrication of solid-state materials with high CPL dissymmetry that can find novel applications in chiroptical sensing, memory, and light-emitting devices based on organic nanoparticles. PMID- 26270704 TI - Multiexciton Solar Cells of CuInSe2 Nanocrystals. AB - Peak external quantum efficiencies (EQEs) of just over 120% were observed in photovoltaic (PV) devices of CuInSe2 nanocrystals prepared with a photonic curing process. The extraction of more than one electron/hole pair as a result of the absorption of a single photon can occur if multiple excitons are generated and extracted. Multiexciton generation (MEG) in the nanocrystal films was substantiated by transient absorption spectroscopy. We propose that photonic curing leads to sufficient electronic coupling between nanocrystals to enable multiexciton extraction under typical solar illumination conditions. Under low light conditions, however, the EQE drops significantly, indicating that photonic curing-induced ligand desorption creates a significant amount of traps in the film that limit the overall power conversion efficiency of the device. PMID- 26270709 TI - Photofunctional Materials Fabricated with Chalcopyrite-Type Semiconductor Nanoparticles Composed of AgInS2 and Its Solid Solutions. AB - Over the past decade, many researchers have made efforts to develop high-quality I-III-VI2 group chalcopyrite-type semiconductor nanoparticles of Cu-based or Ag based materials, such as CuInS2, Cu(InGa)Se2, and AgInS2, due to their low toxicity, wide range of absorption from UV to visible or near-infrared regions, and tunable energy gap depending on the chemical composition. Ag-based chalcopyrite-type nanoparticles have attracted much attention because they have physicochemical properties that can be controlled in a manner similar to that for Cu-based nanoparticles but can be synthesized easily under milder reaction conditions than those of Cu-based ones. In this Perspective, we review recent works relating to the preparation of low-toxic nanoparticles of Ag-based chalcopyrite-type semiconductors and their solid solutions, and then we introduce their application as photofunctional materials. Tunability of optical properties has considerably contributed to recent advances in photofunctional applications of chalcopyrite-type semiconductor nanoparticles to sensors, photocatalysts, and solar cells. PMID- 26270708 TI - Non-Condon Effects on the Doubly Resonant Sum Frequency Generation of Rhodamine 6G. AB - We report first-principles simulations of the doubly resonance sum-frequency generation (DR-SFG) spectrum for rhodamine 6G (R6G). The simulations are done using a time-dependent formalism that includes both Franck-Condon (FC) and Herzberg-Teller (HT) terms in combination with time-dependent density functional theory (TDDFT) calculations. The simulated spectrum matches experiments, allowing a detailed assignment of the DR-SFG spectrum. Our work also shows that non-Condon effects are important and the DR-SFG spectrum of R6G is highly dependent on both FC and HT modes. This is surprising as R6G is known to be a strong FC resonant Raman scatterer. The simulations predict an orientation where the xanthene plane of R6G is perpendicular to the surface with binding through one of the ethyl amine groups. Our results show the importance of first-principles simulations for providing a detailed assignment of DR-SFG experiments, especially for large molecules where such an assignment is complicated due close-lying vibrational modes. PMID- 26270707 TI - Configuration Interaction-Corrected Tamm-Dancoff Approximation: A Time-Dependent Density Functional Method with the Correct Dimensionality of Conical Intersections. AB - Linear response (LR) Kohn-Sham (KS) time-dependent density functional theory (TDDFT), or KS-LR, has been widely used to study electronically excited states of molecules and is the method of choice for large and complex systems. The Tamm Dancoff approximation to TDDFT (TDDFT-TDA or KS-TDA) gives results similar to KS LR and alleviates the instability problem of TDDFT near state intersections. However, KS-LR and KS-TDA share a debilitating feature; conical intersections of the reference state and a response state occur in F - 1 instead of the correct F 2 dimensions, where F is the number of internal degrees of freedom. Here, we propose a new method, named the configuration interaction-corrected Tamm-Dancoff approximation (CIC-TDA), that eliminates this problem. It calculates the coupling between the reference state and an intersecting response state by interpreting the KS reference-state Slater determinant and linear response as if they were wave functions. Both formal analysis and test results show that CIC-TDA gives similar results to KS-TDA far from a conical intersection, but the intersection occurs with the correct dimensionality. We anticipate that this will allow more realistic application of TDDFT to photochemistry. PMID- 26270710 TI - Interface Engineering in Inorganic-Absorber Nanostructured Solar Cells. AB - Nanostructured solar cells have the potential to provide a low-cost alternative to more traditional thin film solar cell technologies. Of particular interest are nanostructured solar cells with inorganic semiconductor absorbers, due to their favorable absorption properties. Such devices include quantum-dot-sensitized solar cells (QDSSCs), extremely thin absorber solar cells (ETASCs), and colloidal quantum dot solar cells (CQDSCs). However, these device architectures suffer from high rates of internal recombination and other problems associated with their extensive internal surface areas. Interfacial surface treatments have proven to be a highly effective means to improve the electronic properties of these devices, leading to overall gains in efficiencies. In this Perspective, we focus on three types of interfacial modification: band alignment by molecular dipole layers, improved CQD film mobilities by ligand exchange, and reduced recombination by interfacial inorganic layers. Select examples in each of these categories are highlighted to provide a detailed look at the underlying mechanisms. We believe that surface modification studies in these devices-QDSSCs, ETASCs, and CQDSCs-are of interest not only to these fields, but also to the broader photovoltaics community. PMID- 26270711 TI - Controlling Interfacial Processes in Excitonic Nanoparticles. PMID- 26270712 TI - Probing Local Structure of Layered Double Hydroxides with (1)H Solid-State NMR Spectroscopy on Deuterated Samples. AB - By using a simple and efficient deuteration process, (2)H has been successfully introduced into layered double hydroxides (LDHs). Due to significantly less (1)H (1)H homonuclear dipolar coupling, high-resolution (1)H solid-state NMR spectra can now be obtained conveniently at medium to low spinning speed to extract the information of cation ordering in LDHs. Furthermore, we show that double resonance experiments can be applied easily to investigate internuclear proximities and test possible cation-ordered superstructure models. This approach can be readily extended to LDHs with different compositions to explore the local structure and the key interactions between the cations in the layer and interlayer anions. PMID- 26270713 TI - Porous Au Nanoparticles with Tunable Plasmon Resonances and Intense Field Enhancements for Single-Particle SERS. AB - Porous Au nanoparticles with fine-controlled overall particle sizes have been fabricated using a kinetically controlled seed-mediated growth method. In contrast to spherical Au nanoparticles with smooth surfaces, the porous Au nanoparticles exhibit far greater size-dependent plasmonic tunability and significantly intensified local electric field enhancements exploitable for single-particle plasmon-enhanced spectroscopies. The effects of the nanoscale porosity on the far- and near-field optical properties of the nanoparticles have been investigated both experimentally by optical extinction and single nanoparticle Raman spectroscopic measurements and theoretically through finite difference time-domain calculations. PMID- 26270714 TI - Impact of Spin-Orbit Coupling on Photocurrent Generation in Ruthenium Dye Sensitized Solar Cells. AB - Relativistic TDDFT calculations have been performed employing a novel computational approach to evaluate the impact of spin-orbit coupling (SOC) in the optical and photovoltaic properties of panchromatic Ru(II) dyes for dye sensitized solar cells (DSCs). The employed computational setup accurately reproduces the optical properties of the investigated dyes, allowing an assessment of the factors responsible for the varying SOC with the dye metal ligand environment. While for the prototypical panchromatic black dye sensitizer a negligible SOC effect is found, the SOC-induced spectral broadening calculated for the recently reported DX1 dye partly enhances the light-harvesting efficiency and consequently the photocurrent generation in DSCs based on this dye. PMID- 26270715 TI - Efficient and Energy-Saving CO2 Capture through the Entropic Effect Induced by the Intermolecular Hydrogen Bonding in Anion-Functionalized Ionic Liquids. AB - A strategy for improving the capture of CO2 was developed through the entropic effect by tuning the geometric construction of anion-functionalized ionic liquids. Several kinds of anion-functionalized ionic liquids with the amino group at the para or ortho position were designed and applied for the capture of CO2, which indicates that the former exhibited both higher capacity and lower enthalpy, resulting in the efficient and energy-saving CO2 capture. Viscosity measurements, spectroscopic investigations, and quantum chemical calculations showed that such a unique behavior originated from the entropic effect, which was induced by the intermolecular hydrogen bonding in these ionic liquids. The entropic control for gas separation developed by this work provides an efficient strategy to both increased capacity and reduced enthalpy. PMID- 26270717 TI - Porous Boron Nitride with Tunable Pore Size. AB - On the basis of a global structural search and first-principles calculations, we predict two types of porous boron-nitride (BN) networks that can be built up with zigzag BN nanoribbons (BNNRs). The BNNRs are either directly connected with puckered B (N) atoms at the edge (type I) or connected with sp(3)-bonded BN chains (type II). Besides mechanical stability, these materials are predicted to be thermally stable at 1000 K. The porous BN materials entail large surface areas, ranging from 2800 to 4800 m(2)/g. In particular, type-II BN material with relatively large pores is highly favorable for hydrogen storage because the computed hydrogen adsorption energy (-0.18 eV) is very close to the optimal adsorption energy (-0.15 eV) suggested for reversible hydrogen storage at room temperature. Moreover, the type-II materials are semiconductors with width dependent direct bandgaps, rendering the type-II BN materials promising not only for hydrogen storage but also for optoelectronic and photonic applications. PMID- 26270716 TI - Vibrational Perturbations and Ligand-Layer Coupling in a Single Crystal of Au144(SC2H4Ph)60 Nanocluster. AB - We have determined vibrational signatures and optical gap of the Au144(PET)60 (PET: phenylethylthiol, SC2H4Ph) nanocluster solvated in deuterated dichloromethane (DCM-D2, CD2Cl2) and in a single crystal. For crystals, solid state (13)C NMR and X-ray diffraction were also measured. A revised value of 2200 cm(-1) (0.27 eV) was obtained for the optical gap in both phases. The vibrational spectra of solvated AU144(PET)60 closely resembles that of neat PET, while the crystalline-state spectrum exhibits significant inhomogeneous spectral broadening, frequency shifts, intensity transfer between vibrational modes, and an increase in the overtone and combination transition intensities. Spectral broadening was also observed in the (13)C NMR spectrum. Changes in the intensity are explained due to vibrational coupling of the normal modes induced by the crystal packing, and the vibrational broadening is caused by ligand-environment inhomogeneity in the crystal. This indicates a pseudocrystalline state where the cluster cores are arranged in periodic fashion, while the ligand-layer molecules between the cores form amorphous structures. PMID- 26270719 TI - Cangrelor inhibits the binding of the active metabolites of clopidogrel and prasugrel to P2Y12 receptors in vitro. AB - Cangrelor is a rapid-acting, direct-binding, and reversible P2Y12 antagonist which has been studied for use during percutaneous coronary intervention (PCI) in patients with or without pretreatment with an oral P2Y12 antagonist. As cangrelor is administered intravenously, it is necessary to switch to an oral P2Y12 antagonist following PCI, such as the thienopyridines clopidogrel, and prasugrel or the non-pyridine ticagrelor. Previous studies have suggested a negative pharmacodynamic interaction between cangrelor and thienopyridines. This in vitro study evaluated the receptor-level interaction between cangrelor and the active metabolite (AM) of clopidogrel or prasugrel by assessing functional P2Y12 receptor number using a (33)P-2MeSADP binding assay. All P2Y12 antagonists studied resulted in strong P2Y12 receptor blockade (cangrelor: 93.6%; clopidogrel AM: 93.0%; prasugrel AM: 97.9%). Adding a thienopyridine AM in the presence of cangrelor strongly reduces P2Y12 receptor blockade by the AM (clopidogrel AM: 7%, prasugrel AM: 3.2%). The thienopyridine AMs had limited ability to compete with cangrelor for binding to P2Y12 (% P2Y12 receptor blockade after co-incubation with cangrelor 1000 nmol/L: 11.7% for clopidogrel AM 3 umol/L; 34.1% for prasugrel AM 3 umol/L). In conclusion, in vitro cangrelor strongly inhibits the binding of clopidogrel and prasugrel AMs to the P2Y12 receptor, consistent with the previous observation of a negative pharmacodynamic interaction. Care may need to be taken to not overlap exposure to thienopyridine AMs and cangrelor in order to reduce the risk of thrombotic complications following PCI. PMID- 26270718 TI - One-Dimensional Singlet Exciton Diffusion in Poly(3-hexylthiophene) Crystalline Domains. AB - Singlet exciton dynamics in crystalline domains of regioregular poly(3 hexylthiophene) (P3HT) films was studied by transient absorption spectroscopy. Upon the selective excitation of crystalline P3HT at the absorption edge, no red shift of the singlet exciton band was observed with an elapse of time, suggesting singlet exciton dynamics in relatively homogeneous P3HT crystalline domains without downhill relaxation in the energetic disorder. Even under such selective excitation conditions, the annihilation rate coefficient gamma(t) was still dependent on time, gamma(t) ? t(-1/2), which is attributed to anisotropic exciton diffusion in P3HT crystalline domains. From the annihilation rate coefficient, the singlet exciton diffusion coefficient D and exciton diffusion length LD in the crystalline domains were evaluated to be 7.9 * 10(-3) cm(2) s(-1) and 20 nm, respectively. The origin of the time-dependent exciton dynamics is discussed in terms of dimensionality. PMID- 26270720 TI - Very Frequent Fallers and Future Fall Injury: Continuous Risk Among Community Dwelling Home Care Recipients. AB - OBJECTIVES: To examine the relationship between falls history, especially those with frequent recent falls, and future injurious falls. METHOD: Resident Assessment Instrument for Home Care records of 167,162 home care recipients in Ontario, Canada, were linked to emergency department records recording an injurious fall. Diagnosis codes further informed the nature of the injuries. RESULTS: Persons with a high number of recent falls tended to be younger, and more likely to have Parkinson's or multiple sclerosis. Odds ratios for a future injurious fall, compared with zero recent falls, were as follows: 1.58 (1 fall), 1.91 (2 or 3 falls), 2.54 (4-8 falls), 3.07 (9 or more falls). Injuries among those with multiple recent falls were more likely to be head injuries with an open wound. DISCUSSION: Persons reporting high number of recent falls were at the greatest risk of a future injurious fall and should receive the greatest attention in care planning. PMID- 26270723 TI - Looking into the Future of the Journal Ultrastructural Pathology: Morphology at its Best. PMID- 26270724 TI - Immunotactoid Glomerulopathy and Cryoglobulinemic Nephropathy: Two Entities with Many Similarities. A Unified Conceptual Approach. AB - Immunotactoid glomerulopathy is a rare disorder that has been characterized at the ultrastructural level. Due to its rarity, there are few comprehensive studies relating to this disorder. Electron microscopy essentially characterizes this disease. The glomerular electron dense deposits which are typical of this condition consist of aggregates of highly organized microtubular structures of various diameters, but generally measuring 30-50 nm in width with a propensity to dispose themselves in parallel bundles intersecting in different planes. This study compares a large series of patients with cryoglobulinemic nephropathy with a series of patients with immunotactoid glomerulopathy to address whether there may be similarities that warrant considering these two entities part of a spectrum. This study reviews the clinicopathologic features of both entities and emphasizes ultrastructural findings that characterize them. Significant immunomorphologic overlap was found when these two disorders were compared in this study. There were also striking similarities in clinical presentation/behavior, laboratory findings and prognosis. Proteomic analysis has also demonstrated similar spectra for both entities. We postulate that immunotactoid glomerulopathy and cryoglobulinemic nephropathy are part of the spectrum of renal manifestations in patients with circulating cryoglobulins and renal disease. PMID- 26270725 TI - Heavy Metal Bioaccumulation in an Atypical Primitive Neuroectodermal Tumor of the Abdominal Wall. AB - Heavy metals are able to interfere with the function of vital cellular components. Besides in trace heavy metals, which are essential at low concentration for humans, there are heavy metals with a well-known toxic and oncogenic potential. In this study, for the first time in literature, we report the unique adulthood case of an atypical primitive neuroectodermal tumor of the abdominal wall, diagnosed by histology and immunohistochemistry, with the molecular hybridization support. The neoplasia occurred in a patient chronically exposed to a transdermal delivery of heavy metal salts (aluminum and bismuth), whose intracellular bioaccumulation has been revealed by elemental microanalysis. PMID- 26270726 TI - Nonplanar Organic Sensitizers Featuring a Tetraphenylethene Structure and Double Electron-Withdrawing Anchoring Groups. AB - Two metal-free organic sensitizers containing two N,N-diethylaniline (DEA) moieties and a twisted 1,1,2,2-tetraphenylethene (TPE) structure, dye SD with one anchoring group and dye DD with two anchoring groups, were synthesized and applied in dye-sensitized solar cells (DSSCs). The introduction of a nonplanar TPE structure was used to form a series of propeller-like structures and reduce the tendency of dyes to randomly aggregate on TiO2 surface, but without importing an aggregation-induced emission (AIE) property. The thermal stabilities, UV-vis absorption spectra, electrochemical properties, and photovoltaic parameters of DSSCs with these two dyes were systematically studied and compared with each other. The overall conversion efficiencies (eta) of 4.56% for dye SD and 6.08% for dye DD were obtained under AM 1.5 G irradiation. PMID- 26270728 TI - Diagnosis of Mastocytosis in Children and Adults in Daily Clinical Practice. AB - Mastocytosis comprises a heterogeneous group of disorders characterized by clonal, neoplastic proliferation of mast cells accumulating in one or multiple organs. In the majority of cases skin involvement is the first clinical manifestation of the disease. Clinical work-up consists of a combination of morphological, immunohistochemical, flow cytometric immunophenotyping and molecular examination. Cutaneous mastocytosis predominates in children, whereas systemic mastocytosis is the most common form of the disease in adults. Therefore, different diagnostic algorithms have to be applied in adult patients and children with suspected mastocytosis. This comprehensive review presents currently defined variants of the disease and recommendations to facilitate diagnostic work-up in children and adults with suspected mastocytosis in daily clinical practice. PMID- 26270729 TI - Conformation, self-aggregation, and membrane interaction of peptaibols as studied by pulsed electron double resonance spectroscopy. AB - Pulsed EPR methods, in particular pulsed electron double resonance (PELDOR) [or double electron-electron resonance (DEER)], are very sensitive to the dipole ... dipole interaction between electron spins in a pair of free radicals. Using PELDOR, the conformations of a number of double radical-containing biomolecules have been determined. In this review article, we focused our attention on the application of this spectroscopy to nitroxide-labeled peptaibols. This is an emerging class of naturally occurring, relatively short, linear, helical peptide molecules endowed with hydrophobic character, capability to interact with and to alter the structure of membranes, and antibiotic activity. We extracted detailed information on the secondary structures of specifically site-directed, double nitroxide-labeled peptaibols under a variety of experimental conditions, including biologically relevant environments. Moreover, we examined in-depth peptaibol clustering, related to the marked propensity of these molecules to undergo self-association in model and whole-cell membrane systems, using mainly mono-nitroxide-containing synthetic analogs. Finally, based on the PELDOR data accumulated, we proposed models of supramolecular (quaternary) structures of peptaibols and their binding modes to membranes. PMID- 26270727 TI - Clinical Actionability of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Risk Assessment. AB - IMPORTANCE: The practice of genetic testing for hereditary breast and/or ovarian cancer (HBOC) is rapidly evolving owing to the recent introduction of multigene panels. While these tests may identify 40% to 50% more individuals with hereditary cancer gene mutations than does testing for BRCA1/2 alone, whether finding such mutations will alter clinical management is unknown. OBJECTIVE: To define the potential clinical effect of multigene panel testing for HBOC in a clinically representative cohort. DESIGN, SETTING, AND PARTICIPANTS: Observational study of patients seen between 2001 and 2014 in 3 large academic medical centers. We prospectively enrolled 1046 individuals who were appropriate candidates for HBOC evaluation and who lacked BRCA1/2 mutations. INTERVENTIONS: We carried out multigene panel testing on all participants, then determined the clinical actionability, if any, of finding non-BRCA1/2 mutations in these and additional comparable individuals. MAIN OUTCOMES AND MEASURES: We evaluated the likelihood of (1) a posttest management change and (2) an indication for additional familial testing, considering gene-specific consensus management guidelines, gene-associated cancer risks, and personal and family history. RESULTS: Among 1046 study participants, 40 BRCA1/2-negative patients (3.8%; 95% CI, 2.8%-5.2%) harbored deleterious mutations, most commonly in moderate-risk breast and ovarian cancer genes (CHEK2, ATM, and PALB2) and Lynch syndrome genes. Among these and an additional 23 mutation-positive individuals enrolled from our clinics, most of the mutations (92%) were consistent with the spectrum of cancer(s) observed in the patient or family, suggesting that these results are clinically significant. Among all 63 mutation-positive patients, additional disease-specific screening and/or prevention measures beyond those based on personal and family history alone would be considered for most (33 [52%] of 63; 95% CI, 40.3%-64.2%). Furthermore, additional familial testing would be considered for those with first-degree relatives (42 [72%] of 58; 95% CI, 59.8% 82.2%) based on potential management changes for mutation-positive relatives. This clinical effect was not restricted to a few of the tested genes because most identified genes could change clinical management for some patients. CONCLUSIONS AND RELEVANCE: In a clinically representative cohort, multigene panel testing for HBOC risk assessment yielded findings likely to change clinical management for substantially more patients than does BRCA1/2 testing alone. Multigene testing in this setting is likely to alter near-term cancer risk assessment and management recommendations for mutation-affected individuals across a broad spectrum of cancer predisposition genes. PMID- 26270730 TI - Chronic Exposure to TNFalpha Impairs Secretion of Glucagon-Like Peptide-1. AB - Obesity is associated with systemic inflammation and elevated levels of TNFalpha, leading to impaired glucose tolerance. In humans, obesity is also associated with reduced nutrient-stimulated secretion of the intestinal incretin hormone, glucagon-like peptide-1 (GLP-1). We hypothesized that TNFalpha plays a direct role in the impairment of GLP-1 secretion from the enteroendocrine L-cell and that blocking TNFalpha can restore both GLP-1 secretion and glucose homeostasis. Expression of the TNFalpha receptor subytpe-1 was detected in the human NCI-H716 and murine GLUTag L-cell models and in mouse ileal sections. Although TNFalpha acutely increased GLP-1 release from NCI-H716 cells (P < .05-.001), preincubation with TNFalpha for 24 hours reduced proglucagon mRNA (P < .05) and GLP-1 cellular (P < .05) levels without affecting cell viability. Furthermore, both NCI-H716 and GLUTag cells pretreated with TNFalpha for 24 hours no longer responded to known GLP-1 secretagogues, an effect that was reversed by coincubation with the Nuclear Factor Kappa B inhibitor, 5-aminosalicylic acid, in the NCI-H716 cells. Mice given a high-fat diet (HFD) for 12 weeks developed impaired glucose tolerance, hyperinsulinemia, and increased TNFalpha mRNA expression in fat and ileal tissue. Hyperglycemia and hyperinsulinemia were reduced in HFD mice treated with the anti TNFalpha biological, etanercept, for 2 weeks. In primary intestinal cultures from these animals, HFD control mice had impaired GLP-1 secretion, and this was not observed in the HFD etanercept-derived cultures (P < .05). In conclusion, chronic exposure to TNFalpha directly impairs GLP-1 secretion at the level of the intestinal L-cell, an effect that is reversed by anti-TNFalpha therapy in association with improved glucose tolerance. PMID- 26270731 TI - Ontogeny of the Saccus Vasculosus, a Seasonal Sensor in Fish. AB - TSH secreted from the pars distalis (PD) of the pituitary gland stimulates the thyroid gland. In contrast, TSH secreted from the pars tuberalis (PT) of the pituitary gland regulates seasonal reproduction. The ontogeny of thyrotrophs and the regulatory mechanisms of TSH are apparently different between the PD and the PT. Interestingly, fish do not have an anatomically distinct PT, and the saccus vasculosus (SV) of fish is suggested to act as a seasonal sensor. Thus, it is possible that the SV is analogous to the PT. Here we examined the ontogeny of the pituitary gland and SV using rainbow trout. A histological analysis demonstrated the development of the pituitary anlage followed by that of the SV. Lhx3 and Pit 1, which are required for the development of PD thyrotrophs, clearly labeled the pituitary anlage. The common glycoprotein alpha-subunit (CGA) and TSH beta subunit (TSHB) genes were also detected in the pituitary anlage. In contrast, none of these genes were detected in the SV anlage. We then performed a microarray analysis and identified parvalbumin (Pvalb) as a marker for SV development. Because Pvalb expression was not detected in the pituitary anlage, no relationship was observed between the development of the SV and the pituitary gland. In contrast to embryos, Lhx3, Pit-1, CGA, and TSHB were all expressed in the adult SV. These results suggest that the morphological differentiation of SV occurs during the embryonic stage but that the functional differentiation into a seasonal sensor occurs in a later developmental stage. PMID- 26270732 TI - The Detection and Species Identification of Blood $mdash; A Bibliography of Relevant Papers from 1980 to 1995. AB - The comprehensive review of the biochemical forensic literature by Gaensslen covered much of the subject until about 1980. This review focuses on two aspects of forensic serology and reports on the progress and research in the identification of blood and its species determination during the period 1980 to 1995. The development of ELISA techniques and the explosive developments in DNA technology have and will change the course of forensic science. The usefulness of these and other techniques has been extended to archaeology as well as other disciplines. While borrowing heavily from the forensic literature, these researchers have produced their own literature which, in turn, is of interest to the forensic scientist. PMID- 26270733 TI - High Performance Liquid Chromatographic Analysis of Enantiomeric Composition of Abuse Drugs. AB - Numerous commonly abused drugs exist in two enantiomeric forms. Identifying the exact enantiomeric form is essential when only one of these two enantiomers is a controlled substance. Enantiomeric composition data may also help the investigation of clandestine laboratory activities. Although generally not as convenient as gas chromatographic methods, liquid chromatographic methods (LC) allow for the selection of larger and hopefully more effective derivatizing groups and the use of an "active" mobile phase. LC-based enantiomeric resolution approaches include derivatization with chiral agents, incorporation of chiral additives in the mobile phase, and the use of chiral stationary phases. Various applications of these approaches are reviewed.Unique detection procedures that were adopted in enantiomeric analysis are also reviewed. PMID- 26270734 TI - Preparation of Hair Samples for Drug Analysis. AB - Toxicological hair analysis has attracted substantial attention because of its promising diagnostic power. Analysis of drugs in hair, even though widely studied since 1970, is still not standardized; many different sample preparation and analytical procedures are practiced. To obtain reliable results, hair analysis requires preparation steps that are not necessary for conventional biological samples such as blood or urine. Pretreatment procedures are mainly conducted to decontaminate hair samples and to isolate drugs from the solid hair structure before instrumental analysis. Many types of sample preparation procedures have been reported in the literature. Selecting an appropriate one can be difficult because the choice depends on different factors, including decontamination efficiency, analytical recovery, and chemical stability of the target drug and its metabolites. This review discusses the main aspects of hair sample preparation procedures through a critical evaluation of literature data, focusing on the procedures, reliability, advantages, and result interpretation. PMID- 26270735 TI - beta-Thalassemia Intermedia Caused by Compound Heterozygosity for Hb Lepore Hollandia and beta-Thalassemia is Rare in the Indian Population. AB - Compound heterozygosity for one of the Hb Lepore mutations and beta-thalassemia (beta-thal) is a rare cause of non transfusion-dependent thalassemia. We report a 4-year-old boy who presented clinically as homozygous/compound heterozygous beta thal intermedia (beta-TI), an impression that was corroborated by the initial hemoglobin (Hb) high performance liquid chromatography (HPLC). However, the correct diagnosis of a rare compound heterozygous Hb Lepore-Hollandia/beta-thal was revealed after parental studies and molecular analyses including beta-globin gene sequencing. Our patient highlights the importance of a logical stepwise multi modality approach and the vital importance of parental screening and molecular studies in accurate characterization of complex hemoglobinopathies. Correct diagnosis is especially crucial if pre natal detection is anticipated for future pregnancies. Molecular analyses alone may not compensate for the unavailability of parental testing. This is because the molecular results may be misinterpreted, especially if limited tests are conducted. The infrequent prior reports of this combination from distant parts of the Indian subcontinent suggests that the origin of Hb Lepore-Hollandia from sporadic mutations occurs in isolated families. PMID- 26270736 TI - A Novel Heme Pocket Hemoglobin Variant Associated with Normal Hematology: Hb Zara or alpha91(FG3)Leu->Ile (alpha2) (HBA2: c.274C > A). AB - We report a new hemoglobin (Hb) variant on the HBA2 gene, Hb Zara [alpha91(FG3)Leu->Ile (alpha2); HBA2: c.274C > A], which was found in a Caucasian man from Croatia. It was observed by routine cation exchange chromatography as an abnormal 21.8% fraction overlapping Hb A2, and associated with normal hematology. It was slightly unstable by the standard isopropanol precipitation test. DNA analysis revealed the CTT > ATT mutation at codon 91 on an alpha2 gene of a normal alpha-globin gene arrangement. This new variant represents the sixth described mutation at codon alpha91 and fourth on the alpha2 locus. As a result of the slight instability due to the significant role of the alpha91 residue in the alpha1beta2 contact, the level of the Hb Zara variant was lower than levels observed for several stable variants codified by the alpha2 locus. PMID- 26270737 TI - First Description of a beta-Thalassemia Mutation, -86 (C > G) (HBB: c.-136C > G), in a Chinese Family. AB - We present the first description of a Chinese family with a beta-thalassemia (beta-thal) mutation -86 (C > G) (HBB: c.-136C > G). This mutation changes the conserved promoter sequence within the proximal CACCC box of the beta-globin gene that leads to a phenotype of beta+-thal. The beta-globin haplotype analysis revealed that the -86 mutation in our case was linked with haplotype I [+ - - - - + +]. This haplotype was commonly found both in the beta-thal mutation and the betaA gene. Our results suggest that the -86 mutation possibly does not have a distinct origin. PMID- 26270738 TI - Self-assembly of Janus ellipsoids: a Brownian dynamics simulation with a quantitative nonspherical-particle model. AB - Janus ellipsoids as mesoscale building blocks can aggregate into various micelle like structures in solution that have potential applications in many fields such as novel surfactants, photonic crystals, drug delivery and biochemical sensors. In this work, we present a novel nonspherical-particle model to investigate the self-assembly of Janus ellipsoids, which quantitatively reflects interaction dependence on the particle shape. The phase diagrams of Janus ellipsoids depending on the aspect ratio and the component ratio are achieved and various aggregates are observed such as a sandwich-type structure, columnar aggregates, vesicles, liquid crystals, random aggregation structures, spherical micelles and wormlike micelles. The specific heat capacity curves and temperature evolutions illustrate the formation processes of assembled superstructures detailedly. We analyze the potential energy surfaces (PESs) of interaction between two Janus ellipsoids and the minimum energy paths (MEPs) between saddle points on the PESs. It is found that the number of metastable conformation and the activation energy along MEPs rely not only on the ellipsoidal shape but also on the component ratio. This work provides rich and valuable information for a deep understanding of the self-assembly mechanism of Janus ellipsoids and design of new mesoscale building blocks. PMID- 26270739 TI - Rhinovirus in the Pathogenesis and Clinical Course of Asthma. AB - In healthy individuals, human rhinovirus (HRV) infections are the major cause of the common cold. These are generally uncomplicated infections except for occasional cases of otitis media or sinusitis. In individuals with asthma, however, HRV infections can have a major impact on disease development and progression. HRV-induced wheezing illnesses in early life are a significant risk factor for subsequent development of asthma, and growing evidence supports a role of recurrent HRV infections in the development and progression of several aspects of airway remodeling in asthma. In addition, HRV infections are one of the most common triggers for acute exacerbations of asthma, which represent a major burden to health-care systems around the world. None of the currently prescribed medications for asthma are effective in preventing or reversing asthma development and airway remodeling or are ideal for treating HRV-induced exacerbations of asthma. Thus, a better understanding of the role of HRV in asthma is important if we are to develop more effective therapies. In the past decade, we have gained new insights into the role of HRV infections in the development and progression of airway remodeling as well as a new appreciation for the proinflammatory and host defense responses to HRV infections that may help to regulate susceptibility to asthma exacerbations. This article reviews the current understanding of the role HRV infections play in the pathogenesis of asthma and identifies possible avenues to new therapeutic strategies for limiting the effects of HRV infections in asthma. PMID- 26270741 TI - Community Member and Stakeholder Perspectives on a Healthy Environment Initiative in North Carolina. AB - INTRODUCTION: The North Carolina Community Transformation Grant Project (NC-CTG) aimed to implement policy, system, and environmental strategies to promote healthy eating, active living, tobacco-free living, and clinical and community preventive services to advance health equity and reduce health disparities for the state's most vulnerable communities. This article presents findings from the Health Equity Collaborative Evaluation and Implementation Project, which assessed community and stakeholder perceptions of health equity for 3 NC-CTG strategies: farmers markets, shared use, and smoke-free multiunit housing. METHODS: In a triangulated qualitative evaluation, 6 photo elicitation (PE) sessions among 45 community members in 1 urban and 3 rural counties and key informant interviews among 22 stakeholders were conducted. Nine participants from the PE sessions and key informant interviews in the urban county subsequently participated in a stakeholder power analysis and mapping session (SPA) to discuss and identify people and organizations in their community perceived to be influential in addressing health equity-related issues. RESULTS: Evaluations of the PE sessions and key informant interviews indicated that access (convenience, cost, safety, and awareness of products and services) and community fit (community-defined quality, safety, values, and norms) were important constructs across the strategies. The SPA identified specific community- and faith-based organizations, health care organizations, and local government agencies as key stakeholders for future efforts. CONCLUSIONS: Both community fit and access are essential constructs for promoting health equity. Findings demonstrate the feasibility of and need for formative research that engages community members and local stakeholders to shape context-specific, culturally relevant health promotion strategies. PMID- 26270740 TI - The Effects of a Beef-Based Meal Compared to a Calorie Matched Bean-Based Meal on Appetite and Food Intake. AB - Protein and fiber have strong satiety-inducing potential. Beef is a high quality, protein-rich food. Beans contain moderate levels of protein as well as fiber. To determine the effects of a high protein meal (beef) compared to a moderate protein, high fiber meal (beans) on subjective appetite and energy intake at a subsequent meal twenty-eight adults, 14 men (ages 24 +/- 5 y, BMI 23 +/- 2 kg/m(2) ) and 14 women (ages 25 +/- 5 y, BMI 22 +/- 2 kg/m(2) ) consumed 2 test lunches containing a "meatloaf" made from either beef or beans. The beef meal provided 26 g of protein and 3 g of fiber while the bean meal provided 17 g of protein and 12 g of fiber. An ad libitum snack was given 3 h after the test meal. Visual analogue scales were used to assess hunger, satiety, fullness, and prospective food intake. Gastrointestinal (GI) tolerance was assessed over 24 h. No difference between the beef and bean was observed for appetite ratings over 3 h, food intake at the subsequent meal (632 +/- 75 kcal compared with 611 +/- 75 kcal, respectively), or sum of GI score (2.2 +/- 0.5 compared with 2.9 +/- 0.5, respectively). Gas and bloating were reported more often after the bean meal than the beef meal (2.0 +/- 0.4 compared with 1.3 +/- 0.4, P value 0.057). A beef based meal with high protein and a bean-based meal with moderate protein and high fiber produced similar satiety, while the bean-based meal resulting in higher, yet moderate, gas and bloating. PMID- 26270742 TI - Availability, Price, and Quality of Fruits and Vegetables in 12 Rural Montana Counties, 2014. AB - We assessed the consumer food environment in rural areas by using the Nutrition Environment Measures Survey for Stores (NEMS-S) to measure the availability, price, and quality of fruits and vegetables. We randomly selected 20 grocery stores (17 rural, 3 urban) in 12 Montana counties using the 2013 US Department of Agriculture's rural-urban continuum codes. We found significant differences in NEMS-S scores for quality of fruits and vegetables; of 6 possible points, the mean quality score was 4.5; of rural stores, the least rural stores had the highest mean quality scores (6.0). Intervention strategies should aim to increase fruit and vegetable quality in rural areas. PMID- 26270744 TI - Efficient Synthesis of Conformationally Restricted Apoptosis Inhibitors Bearing a Triazole Moiety. AB - Apoptosis is a biological process relevant to different human diseases that is regulated through protein-protein interactions and complex formation. Peptidomimetic compounds based on linear peptoids and cyclic analogues with different ring sizes have been previously reported as potent apoptotic inhibitors. Among them, the presence of cis/trans conformers of an exocyclic tertiary amide bond in slow exchange has been characterized. This information encouraged us to perform an isosteric replacement of the amide bond by a 1,2,3 triazole moiety, in which different substitution patterns would mimic different amide rotamers. The syntheses of these restricted analogues have been carried out through an Ugi multicomponent reaction followed by an intramolecular cyclization. The unexpected formation of a beta-lactam scaffold prompted us to study the course of the intramolecular cyclization of the Ugi adducts. In order to modulate this cyclization, a small library of compounds bearing both heterocyclic scaffolds has been synthesized and their activities as apoptosis inhibitors have been evaluated. PMID- 26270745 TI - A framework for the systematic realisation of phenomena for enhanced sensing of radiological and nuclear materials, and radiation. AB - The quest for new sensing phenomena continues because detecting, discriminating, identifying, measuring and monitoring nuclear materials and their radiation from greater range, at lower concentrations, and in a more timely fashion brings greater safety, security and efficiency. The potential phenomena are diverse, and those that have been realised can be found in disparate fields of science, engineering and medicine, which makes the full range difficult to realise and record. The framework presented here offers a means to systematically and comprehensively explore nuclear sensing phenomena. The approach is based on the fundamental concepts of matter and energy, where the sequence starts with the original nuclear material and its emissions, and progressively considers signatures arising from secondary effects and the emissions from associated materials and the environment. Concepts of operations such as active and passive interrogation, and networked sensing are considered. In this operational light, unpacking nuclear signatures forces a fresh look at the sensing concept. It also exposes how some phenomena that exist in established technology may be considered novel based on how they could be exploited rather than what they fundamentally are. This article selects phenomena purely to illustrate the framework and how it can be best used to foster creativity in the quest for novel phenomena rather than exhaustively listing, categorising or comparing any practical aspects of candidate phenomena. PMID- 26270746 TI - Music for insomnia in adults. AB - BACKGROUND: Insomnia is a common sleep disorder in modern society. It causes reduced quality of life and is associated with impairments in physical and mental health. Listening to music is widely used as a sleep aid, but it remains unclear if it can actually improve insomnia in adults. OBJECTIVES: To assess the effects of listening to music on insomnia in adults and to assess the influence of specific variables that may moderate the effect. SEARCH METHODS: We searched CENTRAL, PubMed, Embase, nine other databases and two trials registers in May 2015. In addition, we handsearched specific music therapy journals, reference lists of included studies, and contacted authors of published studies to identify additional studies eligible for inclusion, including any unpublished or ongoing trials. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials that compared the effects of listening to music with no treatment or treatment-as-usual on sleep improvement in adults with insomnia. DATA COLLECTION AND ANALYSIS: Two authors independently screened abstracts, selected studies, assessed risk of bias, and extracted data from all studies eligible for inclusion. Data on pre-defined outcome measures were subjected to meta-analyses when consistently reported by at least two studies. We undertook meta-analyses using both fixed-effect and random-effects models. Heterogeneity across included studies was assessed using the I2 statistic. MAIN RESULTS: We included six studies comprising a total of 314 participants. The studies examined the effect of listening to pre-recorded music daily, for 25 to 60 minutes, for a period of three days to five weeks.Based on the Grades of Recommendations, Assessment, Development and Evaluation (GRADE) approach, we judged the evidence from five studies that measured the effect of music listening on sleep quality to be of moderate quality. We judged the evidence from one study that examined other aspects of sleep (see below) to be of low quality. We downgraded the quality of the evidence mainly because of limitations in design or being the only published study. As regards risk of bias, most studies were at high risk of bias on at least one domain: one study was at high risk of selection bias and one was judged to be at unclear risk; six studies were at high risk of performance bias; three studies were at high risk of detection bias; one study was at high risk of attrition bias and was study was judged to be at unclear risk; two studies were judged to be at unclear risk of reporting bias; and four studies were at high risk of other bias.Five studies (N = 264) reporting on sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI) were included in the meta-analysis. The results of a random-effects meta-analysis revealed an effect in favour of music listening (mean difference (MD) -2.80; 95% confidence interval (CI) -3.42 to -2.17; Z = 8.77, P < 0.00001; moderate-quality evidence). The size of the effect indicates an increase in sleep quality of the size of about one standard deviation in favour of the intervention compared to no treatment or treatment-as usual.Only one study (N = 50; low-quality evidence) reported data on sleep onset latency, total sleep time, sleep interruption, and sleep efficiency. However, It found no evidence to suggest that the intervention benefited these outcomes. None of the included studies reported any adverse events. AUTHORS' CONCLUSIONS: The findings of this review provide evidence that music may be effective for improving subjective sleep quality in adults with insomnia symptoms. The intervention is safe and easy to administer. More research is needed to establish the effect of listening to music on other aspects of sleep as well as the daytime consequences of insomnia. PMID- 26270743 TI - Mall Walking Program Environments, Features, and Participants: A Scoping Review. AB - INTRODUCTION: Walking is a preferred and recommended physical activity for middle aged and older adults, but many barriers exist, including concerns about safety (ie, personal security), falling, and inclement weather. Mall walking programs may overcome these barriers. The purpose of this study was to summarize the evidence on the health-related value of mall walking and mall walking programs. METHODS: We conducted a scoping review of the literature to determine the features, environments, and benefits of mall walking programs using the RE-AIM framework (reach, effectiveness, adoption, implementation, and maintenance). The inclusion criteria were articles that involved adults aged 45 years or older who walked in indoor or outdoor shopping malls. Exclusion criteria were articles that used malls as laboratory settings or focused on the mechanics of walking. We included published research studies, dissertations, theses, conference abstracts, syntheses, nonresearch articles, theoretical papers, editorials, reports, policy briefs, standards and guidelines, and nonresearch conference abstracts and proposals. Websites and articles written in a language other than English were excluded. RESULTS: We located 254 articles on mall walking; 32 articles met our inclusion criteria. We found that malls provided safe, accessible, and affordable exercise environments for middle-aged and older adults. Programmatic features such as program leaders, blood pressure checks, and warm-up exercises facilitated participation. Individual benefits of mall walking programs included improvements in physical, social, and emotional well-being. Limited transportation to the mall was a barrier to participation. CONCLUSION: We found the potential for mall walking programs to be implemented in various communities as a health promotion measure. However, the research on mall walking programs is limited and has weak study designs. More rigorous research is needed to define best practices for mall walking programs' reach, effectiveness, adoption, implementation, and maintenance. PMID- 26270747 TI - Challenges in Subtrochanteric Femur Fracture Management. AB - Subtrochanteric femur fractures present significant treatment challenges. The deforming muscle forces make fracture reduction difficult. Treatment options include cephalomedullary nailing and various types of plate fixation. There is a high rate of treatment complications, including malunion, delayed union, nonunion, and implant failure. PMID- 26270748 TI - Hip Resurfacing Implants. AB - EDUCATIONAL OBJECTIVES As a result of reading this article, physicians should be able to: 1. Describe the advantages of hip resurfacing. 2. Describe the disadvantages of hip resurfacing. 3. Identify the population in which hip resurfacing is most often indicated. 4. Demonstrate how to properly postoperatively manage patients with metal-on-metal prostheses. Hip resurfacing offers a suitable solution for young patients affected by hip disease who have high function demands and good bone quality. Bone stock preservation, restoration of the normal proximal femur anatomy, the lack of stress shielding, and the possibility of resuming sporting activity are proven advantages of hip resurfacing. However, there are some disadvantages, such as fracture of the femoral neck, onset of neck narrowing, and possible complications due to the metal-on-metal bearings, including pseudotumors, peri-implant osteolysis, and chronic elevation of metal ions in serum levels. Recent data suggest that the ideal candidate for hip resurfacing is an active male, younger than 65 years, with primary or posttraumatic osteoarthritis, and with a femoral head diameter larger than 50 to 54 mm. Based on these selection criteria, the literature reports implant survival to be similar to that of total hip arthroplasty. The current authors' experience confirms a low failure rate and excellent functional outcomes, with metal ion serum levels becoming stable over time in well functioning implants. Proper surgical technique, correct patient selection, and the right choice of a well-established prosthetic model are essential elements for the long-term success of these implants. PMID- 26270749 TI - Anatomical Double-Bundle Coracoclavicular Reconstruction in Chronic Acromioclavicular Dislocation. AB - The purpose of this study was to evaluate the clinical and radiological outcomes of anatomical double-bundle coracoclavicular (CC) reconstruction using the coracoacromial (CA) ligament and the conjoined tendon for the treatment of chronic acromioclavicular (AC) joint dislocation. A retrospective evaluation was performed on 18 patients who underwent an anatomical CC reconstruction using the CA ligament and the conjoined tendon for chronic AC joint dislocation. Patients were treated surgically between April 2007 and January 2012. Mean follow-up was 35.3 months (range, 24-49 months). All patients were evaluated for functional outcomes using the modified University of California, Los Angeles (UCLA) shoulder rating scale for chronic AC injury and the Constant-Murley shoulder outcome score. Range of motion and shoulder and elbow strength were also measured. Plain radiographs were taken to evaluate reduction status and CC distance. Mean modified UCLA shoulder rating scale at final follow-up was 18.1 points (range, 13 20 points). No significant difference in mean Constant-Murley scores existed between the injured and contralateral shoulders (P=.26). At final follow-up, 15 (83.3%) patients had well-maintained reduction and 2 (11.1%) patients had a partial loss of reduction. One other patient had a complete loss of reduction due to a postoperative fall. The CC distance was not significantly different between the injured and contralateral shoulders in the immediate postoperative period (P=.46) or at final follow-up (P=.14). One superficial wound infection occurred and was treated with routine wound care. An anatomical double-bundle CC reconstruction using the CA ligament and the conjoined tendon for the treatment of chronic AC joint dislocation is a reliable surgical method with good results. PMID- 26270750 TI - Polyaxial Screws in Locked Plating of Tibial Pilon Fractures. AB - This study examined the axial and torsional stiffness of polyaxial locked plating techniques compared with fixed-angle locked plating techniques in a distal tibia pilon fracture model. The effect of using a polyaxial screw to cross the fracture site was examined to determine its ability to control relative fracture site motion. A laboratory experiment was performed to investigate the biomechanical stiffness of distal tibia fracture models repaired with 3.5-mm anterior polyaxial distal tibial plates and locking screws. Sawbones Fourth Generation Composite Tibia models (Pacific Research Laboratories, Inc, Vashon, Washington) were used to model an Orthopaedic Trauma Association 43-A1.3 distal tibia pilon fracture. The polyaxial plates were inserted with 2 central locking screws at a position perpendicular to the cortical surface of the tibia and tested for load as a function of axial displacement and torque as a function of angular displacement. The 2 screws were withdrawn and inserted at an angle 15 degrees from perpendicular, allowing them to span the fracture and insert into the opposing fracture surface. Each tibia was tested again for axial and torsional stiffness. In medial and posterior loading, no statistically significant difference was found between tibiae plated with the polyaxial plate and the central screws placed in the neutral position compared with the central screws placed at a 15 degrees position. In torsional loading, a statistically significant difference was noted, showing greater stiffness in tibiae plated with the polyaxial plate and the central screws placed at a 15 degrees position compared with tibiae plated with the central screws placed at a 0 degrees (or perpendicular) position. This study showed that variable angle constructs show similar stiffness properties between perpendicular and 15 degrees angle insertions in axial loading. The 15 degrees angle construct shows greater stiffness in torsional loading. PMID- 26270752 TI - The Quality of Cost-Utility Analyses in Orthopedic Trauma. AB - As health care in the United States transitions toward a value-based model, there is increasing interest in applying cost-effectiveness analysis within orthopedic surgery. Orthopedic trauma care has traditionally underemphasized economic analysis. The goals of this review were to identify US-based cost-utility analysis in orthopedic trauma, to assess the quality of the available evidence, and to identify cost-effective strategies within orthopedic trauma. Based on a review of 971 abstracts, 8 US-based cost-utility analyses evaluating operative strategies in orthopedic trauma were identified. Study findings were recorded, and the Quality of Health Economic Studies (QHES) instrument was used to grade the overall quality. Of the 8 studies included in this review, 4 studies evaluated hip and femur fractures, 3 studies analyzed upper extremity fractures, and 1 study assessed open tibial fracture management. Cost-effective interventions identified in this review include total hip arthroplasty (over hemiarthroplasty) for femoral neck fractures in the active elderly, open reduction and internal fixation (over nonoperative management) for distal radius and scaphoid fractures, limb salvage (over amputation) for complex open tibial fractures, and systems-based interventions to prevent delay in hip fracture surgery. The mean QHES score of the studies was 79.25 (range, 67-89). Overall, there is a paucity of cost-utility analyses in orthopedic trauma; however, the available evidence suggests that certain operative interventions can be cost effective. The quality of these studies, however, is fair, based on QHES grading. More attention should be paid to evaluating the cost-effectiveness of operative intervention in orthopedic trauma. PMID- 26270751 TI - Pitching Speed and Glenohumeral Adaptation in High School Pitchers. AB - Glenohumeral internal rotational deficit and increased glenohumeral external rotation are common findings in baseball pitchers. To the authors' knowledge, no study has focused on the adaptation of glenohumeral internal rotational deficit and increased glenohumeral external rotation in relation to pitching speed. This study evaluated changes in range of motion in the throwing shoulder in high school pitchers to determine whether changes in internal and external rotation directly correlate with pitch velocity. The shoulders of 22 high school varsity pitchers were evaluated. Standard goniometric technique was used to measure passive external and internal glenohumeral range of motion in both arms. Measurements were evaluated for statistically significant differences in range of motion. Demographic features, including height, weight, and age, were assessed. Fifteen consecutive in-game pitch speeds were recorded, and the fastest pitch was used for evaluation. Pitch speeds were correlated to the player's glenohumeral internal rotational deficit, increased glenohumeral external rotation, and physical demographics. Average age was 16.9 years. Average external rotation of the throwing arm was significantly greater than that of the nonthrowing arm (143.00 degrees vs 130.32 degrees , P=.005). Average internal rotation of the throwing arm was significantly less than that of the nonthrowing arm (49.50 degrees vs 65.90 degrees , P=.006). Both shoulders had similar total arc of motion (throwing shoulder, 192.54; nonthrowing shoulder, 196.23; P=.822). Average maximum velocity was 77.7 mph (maximum, 88 mph; minimum, 66 mph). Maximum pitch velocity did not correlate with changes in glenohumeral internal rotational deficit (P=.683) or increased glenohumeral external rotation (P=.241). There was also no evidence of correlation between pitch velocity and player age, height, weight, or dominant hand. The stress of pitching creates adaptations to the throwing shoulder, even in young athletes. There appears to be no significant correlation with a pitcher's maximum velocity and the amount of adaptation in shoulder range of motion. PMID- 26270754 TI - Outcome Measures in Total Joint Arthroplasty: Current Status, Challenges, and Future Directions. AB - Total joint arthroplasty (TJA) is the most commonly performed surgical procedure for the treatment of advanced degenerative joint diseases. Numerous outcome measures for TJA have been developed, which can be reported by physicians, patients, or both. Although outcome tools were traditionally centered on morbidity, mortality, and implant survival, the focus has evolved over recent years to joint-specific, disease-specific, activity-specific, general well-being, and quality of life assessments. However, despite the importance of outcome measures in a time of growing demand for TJA and increased government scrutiny fueled by high implant costs, there remains no "gold standard" method to assess the impact of TJA. The aim of this review is to evaluate the currently available literature on outcome measures in joint arthroplasty, highlighting the strengths and limitations of commonly used instruments. Because outcomes are influenced by a multitude of intangible factors, there is an increasing role for assessing patient satisfaction as a simple way to account for the complex aspects of care. Strategies including proper patient selection and establishing realistic expectations preoperatively are critical to optimizing outcomes. In an era of increasing public scrutiny, the current state of conflicting results and variable correlations among outcome measures implores the need for a standardized system that should incorporate a metric for patient satisfaction adjusted for preoperative expectations. PMID- 26270753 TI - Minimal Preoperative Degenerative Arthritis May Not Predict Poor TKA Outcome. AB - Although most orthopedic surgeons presume that patients with more severe degenerative osteoarthritis are better candidates for total knee arthroplasty (TKA), few data have compared outcomes based on the extent of radiographic osteoarthritis. The authors tested the hypothesis that patients with minimal radiographic osteoarthritis would have worse outcomes compared with a matched cohort with severe osteoarthritis. The authors identified 29 patients (31 knees) with minimal degenerative changes who underwent TKA between 2000 and 2004. The authors identified a matched cohort with severe osteoarthritis. Mean follow-up was 5 years (range, 2-10 years). Preoperative knee scores were 63 and 59 in patients with minimal osteoarthritis and severe osteoarthritis, respectively. Postoperative knee scores were 89 and 93, respectively. Preoperative function scores were 57 and 56 in patients with minimal osteoarthritis and severe osteoarthritis, respectively. Postoperative function scores increased to 79 and 72, respectively. Of 31 patients in the minimal osteoarthritis group, 26 (84%) had mild or no pain at the time of last follow-up, whereas 5 (16%) had moderate or severe pain. In the group with severe osteoarthritis, 25 of 31 patients (81%) had mild or no pain at the time of last follow-up, whereas 6 (19%) had moderate or severe pain. In the group with minimal osteoarthritis, 6 of 31 knees (19%) had a complication. Only 1 of 31 knees (3.1%) in the matched cohort had a complication. Fewer than 1% of patients undergoing TKA at the authors' institution had minimal preoperative radiographic osteoarthritis. These patients had a higher risk of complications, but similar pain relief, function, and overall satisfaction compared with a matched group with severe arthritis. PMID- 26270755 TI - Rotation and Displacement Predict Adverse Events in Pediatric Supracondylar Fractures. AB - The goal of this study was to identify supracondylar fracture patterns that were predictive of adverse events and poor outcomes. The study consisted of a retrospective review of patients admitted for surgical treatment of a supracondylar humerus fracture between June 2008 and August 2010. Preoperative radiographs were assessed based on appearance (simple vs oblique vs comminuted), coronal plane displacement (angulated, posterior, posteromedial vs posterolateral), and rotation (rotation vs no rotation). Logistic regression models were used to examine the relationship between fracture pattern and clinical outcome parameters in 373 patients who were followed for 4 weeks or more postoperatively. Outcome parameters included postoperative complications (infection, delayed healing, pin migration, revision surgery), need for physical or occupational therapy, need for postoperative intravenous narcotics, and preoperative nerve injury. Rotation and coronal displacement patterns of the fracture segments were significantly associated with postoperative complications, postoperative need for physical or occupational therapy as a result of residual stiffness, and nerve injury (P<.05). Compared with posteriorly displaced fractures, posterolaterally displaced fractures were associated with significantly greater odds of complications (P=.045), need for physical or occupational therapy (P<.001), and nerve injury (P<.001). Additionally, fractures with rotation were associated with significantly greater odds of complications (P<.001), need for physical or occupational therapy (P<.001), and nerve injury (P<.001) compared with fractures without rotation. Rotation and coronal plane displacement were predictive of complications, need for physical or occupational therapy, and nerve injury, and thus should be considered as potential prognostic variables when evaluating the initial injury pattern. PMID- 26270757 TI - Reverse Shoulder Arthroplasty for Management of Postinfectious Arthropathy With Rotator Cuff Deficiency. AB - Treatment of patients with rotator cuff deficiency and arthritis in the setting of a prior glenohumeral infection (postinfectious arthropathy) is complex, with little evidence to guide treatment. The current authors present their approach to management of these patients and clinical outcomes after reverse shoulder arthroplasty (RSA). All primary RSAs performed for postinfectious arthropathy and rotator cuff deficiency with native glenohumeral joints were identified in a prospective shoulder arthroplasty registry. Eight patients with a minimum of 2 year follow-up were included in the analysis. Clinical outcomes, including the Constant score, the American Shoulder and Elbow Surgeons (ASES) score, the Western Ontario Osteoarthritis Shoulder (WOOS) index, the Single Assessment Numeric Evaluation (SANE) score, and range of motion measurements, were assessed preoperatively and at final follow-up. At an average follow-up of 4.4 years, no patient had a clinically detectable recurrence of infection. Significant improvements were noted in all outcome scores from preoperative evaluation to final follow-up after RSA, including Constant score (P=.003), ASES score (P<.001), WOOS index (P=.002), SANE score (P=.025), forward flexion (P<.001), abduction (P<.001), and external rotation (P=.020). Seven of 8 patients reported they were satisfied or very satisfied at final follow-up. Reverse shoulder arthroplasty can be performed in patients without significant medical comorbidities in the setting of postinfectious arthropathy and rotator cuff deficiency with a low risk of recurrence of infection. Significant clinical improvements were noted at short-term follow-up. PMID- 26270756 TI - Femoral Neck Fracture After Arthroscopic Femoroplasty of the Hip. AB - Hip arthroscopy is an increasingly common procedure, particularly for the treatment of femoroacetabular impingement. Various complications have been previously reported, and the authors sought to further evaluate the safety of this procedure. This study was conducted to identify the incidence of femoral neck fracture as well as treatment and outcomes after arthroscopic femoroplasty. In April 2013, a survey was administered to 28 established hip arthroscopists regarding the breadth of their experience, including the total number of hip arthroscopies and proximal femoroplasties performed and the number of postoperative femoral neck fractures. Fracture type, patient age, patient sex, time to fracture, comorbidities, treatments, and outcomes were queried. The study identified 27,200 total arthroscopies and 14,945 proximal femoroplasties performed by the surgeons, with 11 postoperative proximal femur fractures. The incidence of proximal femur fracture after arthroscopic femoroplasty was 0.07%, based on combined data of high-volume hip arthroscopists at multiple medical centers. Mean time to fracture after arthroscopic femoroplasty was 40.5 (+/-26.6) days postoperatively. The male-to-female ratio was approximately 1:3 for those with fracture, and mean patient age was 52 (+/-13) years. More than half of the fractures were caused by violation of weight-bearing precautions. All patients had improvement in symptoms after treatment. Femoral neck fracture after arthroscopic femoroplasty is a rare complication for established hip arthroscopists. It is most common in women and patients older than 50 years. Treatment is based on the severity of the fracture, and patients have improved outcomes after treatment. PMID- 26270758 TI - Optimal Management of High-Energy Pilon Fractures. AB - The ideal treatment method for fibular fractures associated with high-energy pilon injuries remains unknown. In this investigation, the authors reviewed a consecutive series of 137 patients who sustained high-energy pilon injuries and assessed the effect of fibular fixation and timing on radiographic and clinical outcomes. At a mean follow-up of 18.7 months, the authors found that the presence or lack of fibular fixation did not have an effect on the timing or rate of union of the pilon fractures; similarly, there was no significant difference between these groups regarding the presence or development of coronal or sagittal malalignment intraoperatively or at final follow-up. Fibular union rates were also not significantly different between groups, but fibular fixation increased operative time in a statistically significant manner. Interestingly, when comparing fibular fixation during the temporization stage vs the definitive fixation stage, the authors found that early fixation of the fibular fracture also had no effect on alignment, healing, or complication rates. Fixation of the fibula during external fixation placement statistically increased operative time during temporization but did not significantly decrease operative time during definitive stabilization. The authors cannot recommend fibular fixation with all associated pilon fractures because the presence or timing of fibular fixation does not significantly change the radiographic outcomes, complication rate, or need for future surgical interventions. Future clinical analysis is needed to further delineate the indication for fibular fixation in this scenario. PMID- 26270759 TI - Short-term Results of Birmingham Hip Resurfacing in the United States. AB - Previous data on the survivorship of the Birmingham Hip Resurfacing (BHR) implant have come from design surgeons and large national databases outside of the United States, and there is a lack of reported outcomes of surface replacement arthroplasty from US centers. A retrospective study was undertaken of 1271 hips treated with a BHR system (Smith & Nephew, Memphis, Tennessee) between June 2006 and September 2008 at 6 high-volume total joint centers in the United States. Demographic features, Harris Hip Score (HHS), and radiographic findings were recorded. Patients who did not have a 2-year follow-up visit were contacted by telephone. All patients were asked about complications, reoperations, or failure of the implants. Of the treated hips, 1144 (90%) had a minimum of 2 years of clinical follow-up (mean, 2.9 years; range, 1.8-4.2 years). Mean age was 52.3 years, and 75% of patients were men. Mean HHS improved from 55.8 preoperatively to 97.4 at the most recent follow-up (P<.001). There were 16 (1.4%) revisions to total hip arthroplasty (THA) for fracture (7), early dislocation (3), acetabular component malpositioning with pain (3; 1 with metallosis), infection (1), femoral loosening (1), and pseudotumor (1). There were 9 additional complications (0.8%) that did not require revision, including 3 dislocations treated with closed reduction, 2 fractures, 3 nerve injuries, and 1 pseudotumor. At 2 to 4 years of follow-up, the revision rate and the major complication rate with the BHR system were similar to those in previous reports of primary THA. Excellent clinical results were observed, but further follow-up is necessary to assess mid- and long term results with the BHR system in US patients. PMID- 26270760 TI - Ultrasound for Infants at Risk for Developmental Dysplasia of the Hip. AB - The best screening method for developmental dysplasia of the hip is controversial. Ultrasonography is sensitive, but cost-effectiveness may limit its use. This study assessed whether ultrasound screening would increase in effectiveness if targeted toward infants with established risk factors for developmental dysplasia of the hip and normal findings on physical examination. All ultrasound scans performed at the authors' institution from January 2007 through January 2011 to screen for developmental dysplasia of the hip were reviewed. Infants with risk factors for developmental dysplasia of the hip and normal findings on physical examination by orthopedic faculty or a pediatrician were selected. Of the 530 cases that were reviewed, 217 had risk factors for developmental dysplasia of the hip and normal findings on physical examination. Mean age of the 217 selected patients was 6.9 weeks. Of the patients, 83% were female, 77% had breech presentation, 30% were firstborn children, 13% had intrauterine packaging abnormalities, and 3% had a family history of developmental dysplasia of the hip. Of the 217 infants, 44 had 1 risk factor, 121 had 2 risk factors, 46 had 3 risk factors, and 6 had 4 risk factors. Dynamic ultrasound evaluation showed instability in 17 patients, for a 7.8% incidence of developmental dysplasia of the hip. All 17 patients were treated with a Pavlik harness. The results suggested that selective ultrasound screening may be effective in infants with risk factors and normal findings on physical examination. Selective ultrasound screening changed treatment management in almost 8% of patients and clinical follow-up in 6.5%. Analysis of the cost effectiveness of screening is needed. PMID- 26270761 TI - Thin-Walled Cross-Linked Acetabular Liners Need Not Exhibit Reduced Locking Strength. AB - Use of larger diameter femoral heads has emerged as a promising strategy to reduce the risk of dislocation after total hip arthroplasty, but thinning the walls of cross-linked ultra-high-molecular-weight polyethylene (UHMWPE) acetabular liners to accommodate these larger heads may compromise the locking mechanism of the liner. The purpose of this study was to test the mechanical integrity of the locking mechanism in cross-linked and re-melted UHMWPE acetabular components with reduced wall thickness. The locking mechanism of cross linked (100 kGy/re-melted) acetabular liners in sizes 50/28, 50/36, and 52/36 mm of 1 design was evaluated by lever-out tests and torsion tests. Torsion tests were performed at 2 angles to isolate the liner's locking tabs independent of the contribution of its central post. Lever-out testing demonstrated nominally reduced failure strength in 50/36-mm liners (13.3 N . m) compared with 50/28-mm liners (12.3 N . m; P=.0502), whereas the lever-out strength of 52/36-mm liners was 12.2+/-0.94 N . m. Failure torques were similar between 50/28- and 50/36-mm liners at 45 degrees and 90 degrees , but the failure torque of size 52/36-mm liners was significantly higher at each angle. The use of larger diameter femoral heads does not compromise the locking mechanism of thinned MicroSeal (Signal Medical Corp, Marysville, Michigan) acetabular liners. Use of a cross-linked UHMWPE acetabular liner, with a locking mechanism that is not compromised when the liner is thinned to a thickness of at least 2.86 mm, appears to be a biomechanically sound construct when articulated with large diameter femoral heads. PMID- 26270762 TI - Successful Bone Healing of Nonunion After Ulnar Shortening Osteotomy for Smokers Treated With Teriparatide. AB - Ulnar shortening osteotomy is widely performed as the standard surgical treatment for ulnar impaction syndrome and has a high percentage of success for pain relief. However, delayed union and nonunion of the osteotomy site remain the most concerning complications. In particular, smokers have a higher incidence of nonunion, which amounts to 30% of cases. For the treatment of nonunion, secondary surgical interventions such as bone grafting will be necessary but are extremely challenging. Recently, teriparatide (recombinant human parathyroid hormone [PTH 1 34]) administration has been reported in several clinical studies as a noninvasive pharmacological systemic treatment for fracture healing or nonunion. The authors present 2 cases of smokers, a 62-year-old man and a 42-year-old woman, with nonunion after ulnar shortening osteotomy and fixation with 6-hole non-locking plate for ulnar impaction syndrome. For treatment of nonunion, noninvasive therapy with teriparatide (20-ug, subcutaneous injection) in addition to low-intensity pulsed ultrasound was underwent. In both cases, partial bone union began to be observed on radiographs after the first 4 weeks of teriparatide administration and successful bone healing without additional surgical interventions was achieved after 10 and 6 months of treatment with teriparatide, respectively. The current case reports showed that non-invasive combination therapy of teriparatide and low-intensity pulsed ultrasound were a possible alternative to surgical intervention. In the future, teriparatide therapy might be applied actively to patients who have risk factors for delayed union, such a heavy smoking habit, and are expected to experience nonunion after ulnar shortening osteotomy. PMID- 26270763 TI - Displaced Medial and Lateral Bucket Handle Meniscal Tears With Intact ACL and PCL. AB - Bucket handle lesions are vertical longitudinal tears in the meniscus that may displace centrally into the respective medial or lateral compartment, frequently causing mechanical symptoms, including pain, perceived instability, and mechanical locking. Bucket handle meniscal tears are most commonly from a traumatic etiology and are frequently found with concomitant anterior cruciate ligament (ACL) injuries. Multiple imaging signs and associations have been described for the diagnosis of bucket handle meniscus tears, including coronal truncation, absent bow tie sign, double posterior cruciate ligament (PCL), double ACL, displacement of the bucket handle fragment, and disproportionate posterior horn signs. Among meniscal pathology encountered on magnetic resonance imaging or during arthroscopy, bucket handle meniscal tears are infrequent occurrences. Furthermore, the occurrence of displaced medial and lateral bucket handle tears found on imaging and during arthroscopy is very uncommon and is only sparsely reported in the literature. When displaced medial and lateral bucket handle meniscal segments are visualized within the intercondylar notch along with the ACL and PCL, the radiologic findings are referred to as the "quadruple cruciate" sign or the "Jack and Jill lesion." Of the few case reports described in the literature, only one noted displaced medial and lateral bucket handle meniscus tears with an intact ACL and PCL. The current case report outlines a similar rare case of the quadruple cruciate sign: displaced medial and lateral bucket handle meniscal tears located within the intercondylar notch and an intact ACL and PCL. PMID- 26270764 TI - Corrective Osteotomy for Ipsilateral Distal Clavicular and Coracoid Malunions. AB - Malunion after double disruption injuries of the superior shoulder suspensory complex accompanied by shoulder pain and dysfunction has been reported infrequently. A 37-year-old man had a double disruption injury (fractures of the distal clavicle and the base of the coracoid process). Conservative treatment resulted in malunion. Twelve months after the injury, pain continued in the coracoclavicular interval, and there was only 125 degrees forward shoulder elevation. Radiographs showed 50 degrees inferior angulation of the distal clavicle and elongated base of the coracoid process. Corrective osteotomy was required; however, the concomitant malunion of the coracoid prevented correction of the deformity with osteotomy of the distal clavicle alone. Therefore, osteotomy of the coracoid was performed. Twelve months postoperatively, successful bone union resulted in loss of pain. Forward elevation had recovered to 160 degrees . Distal clavicular fractures with concomitant coracoid fractures are often significantly displaced, which disrupts physiologic coupling of clavicular and scapular motion and limits forward elevation. In the case of such malunions, excessive movement at the clavicle-scapula junction during mobilization causes pain in the coracoclavicular interval. Correction of this deformity requires osteotomy of both the clavicular and coracoid malunions. PMID- 26270768 TI - Facile Fabrication of Anodic Alumina Rod-Capped Nanopore Films with Condensate Microdrop Self-Propelling Function. AB - We report that aluminum surfaces can be endowed with condensate microdrop self propelling (CMDSP) function by one-step voltage-rising mild anodization in hot phosphoric acid solution followed by fluorosilane modification. Via regulating reaction parameters, we can achieve anodic alumina self-standing rod-capped nanopore films and minimize their solid-liquid interface adhesion. Such low adhesive nanostructured film owns remarkable CMDSP function, especially to condensate microdrops with sizes below 50 MUm, differing from usual gravity driven dropwise condensation on flat aluminum surfaces. Clearly, this work offers a facile, efficient, and industry-compatible approach to processing CMDSP aluminum materials, which is significant for developing innovative energy-saving air-conditioner heat exchangers. PMID- 26270765 TI - A critical reappraisal of dietary practices in methylmalonic acidemia raises concerns about the safety of medical foods. Part 1: isolated methylmalonic acidemias. AB - PURPOSE: Medical foods for methylmalonic acidemias (MMAs) and propionic acidemias contain minimal valine, isoleucine, methionine, and threonine but have been formulated with increased leucine. We aimed to assess the effects of imbalanced branched-chain amino acid intake on metabolic and growth parameters in a cohort of patients with MMA ascertained via a natural history study. METHODS: Cross sectional anthropometric and body-composition measurements were correlated with diet content and disease-related biomarkers in 61 patients with isolated MMA (46 mut, 9 cblA, and 6 cblB). RESULTS: Patients with MMA tolerated close to the recommended daily allowance (RDA) of complete protein (mut(0): 99.45 +/- 32.05% RDA). However, 85% received medical foods, in which the protein equivalent often exceeded complete protein intake (35%). Medical food consumption resulted in low plasma valine and isoleucine concentrations, prompting paradoxical supplementation with these propiogenic amino acids. Weight- and height-for-age z scores correlated negatively with the leucine-to-valine intake ratio (r = -0.453; P = 0.014; R(2) = 0.209 and r = -0.341; P = 0.05; R(2) = 0.123, respectively). CONCLUSION: Increased leucine intake in patients with MMA resulted in iatrogenic amino acid deficiencies and was associated with adverse growth outcomes. Medical foods for propionate oxidation disorders need to be redesigned and studied prospectively to ensure efficacy and safety.Genet Med 18 4, 386-395. PMID- 26270766 TI - A critical reappraisal of dietary practices in methylmalonic acidemia raises concerns about the safety of medical foods. Part 2: cobalamin C deficiency. AB - PURPOSE: Cobalamin C (cblC) deficiency impairs the biosynthesis of 5' deoxyadenosyl-adenosyl- and methyl-cobalamin, resulting in methylmalonic acidemia combined with hyperhomocysteinemia and hypomethioninemia. However, some patients with cblC deficiency are treated with medical foods, devoid of methionine and high in leucine content, that are formulated for patients with isolated propionate oxidative defects. We examined the effects of imbalanced branched chain amino acid intake on growth outcomes in cblC-deficient patients. METHODS: Dietary intake was correlated with biochemical, anthropometric, and body composition measurements and other disease parameters in a cohort of 28 patients with early-onset cblC deficiency. RESULTS: Protein-restricted diets were followed by 21% of the patients, whereas 32% received medical foods. Patients on protein restricted diets had lower height-for-age z-score (P = 0.034), whereas patients consuming medical foods had lower head circumference Z-scores (P = 0.037), plasma methionine concentrations (P = 0.001), and predicted methionine influx through the blood-brain barrier Z-score (-1.29 vs. -0.0617; P = 0.007). The combination of age at diagnosis, a history of seizures, and the leucine-to-valine dietary intake ratio best predicted head circumference Z-score based on multiple regression modeling (R(2) = 0.945). CONCLUSIONS: Patients with cblC deficiency treated with medical foods designed for isolated methylmalonic acidemia are at risk for iatrogenic methionine deficiency that could adversely affect brain growth and development.Genet Med 18 4, 396-404. PMID- 26270767 TI - A semiquantitative metric for evaluating clinical actionability of incidental or secondary findings from genome-scale sequencing. AB - PURPOSE: As genome-scale sequencing is increasingly applied in clinical scenarios, a wide variety of genomic findings will be discovered as secondary or incidental findings, and there is debate about how they should be handled. The clinical actionability of such findings varies, necessitating standardized frameworks for a priori decision making about their analysis. METHODS: We established a semiquantitative metric to assess five elements of actionability: severity and likelihood of the disease outcome, efficacy and burden of intervention, and knowledge base, with a total score from 0 to 15. RESULTS: The semiquantitative metric was applied to a list of putative actionable conditions, the list of genes recommended by the American College of Medical Genetics and Genomics (ACMG) for return when deleterious variants are discovered as secondary/incidental findings, and a random sample of 1,000 genes. Scores from the list of putative actionable conditions (median = 12) and the ACMG list (median = 11) were both statistically different than the randomly selected genes (median = 7) (P < 0.0001, two-tailed Mann-Whitney test). CONCLUSION: Gene-disease pairs having a score of 11 or higher represent the top quintile of actionability. The semiquantitative metric effectively assesses clinical actionability, promotes transparency, and may facilitate assessments of clinical actionability by various groups and in diverse contexts.Genet Med 18 5, 467-475. PMID- 26270770 TI - Metallonaphthalocyanines as triplet sensitizers for near-infrared photon upconversion beyond 850 nm. AB - In triplet-triplet annihilation-based photon upconversion (TTA-UC), the utilization of near-infrared (NIR) light with a wavelength longer than 850 nm remains an outstanding issue. We realized this by employing metallonaphthalocyanines as triplet sensitizers; upon excitation of NIR light (856 nm), upconverted emission was observed in the visible range with remarkable photostability. PMID- 26270769 TI - Potential Use of Thioalkylated Mannose-Modified Dendrimer (G3)/alpha-Cyclodextrin Conjugate as an NF-kappaB siRNA Carrier for the Treatment of Fulminant Hepatitis. AB - NF-kappaB and its associated pathways are complicatedly concerned about hepatic homeostasis. Discriminating inhibition of NF-kappaB signaling has been expected to treat various liver diseases including fulminant hepatitis. To clarify the potential use of thioalkylated mannose-appended dendrimer (generation 3; G3) conjugates with alpha-cyclodextrin with average degree of substitution of mannose (DSM4) (Man-S-alpha-CDE (G3, DSM4)) as a novel antigen presenting cell (APC) specific siRNA carrier, we evaluated the RNAi effect of NF-kappaB p65 siRNA (sip65) complex with Man-S-alpha-CDE (G3, DSM4) both in vitro and in vivo. Man-S alpha-CDE (G3, DSM4)/sip65 complex significantly suppressed NF-kappaB p65 mRNA expression and nitric oxide (NO) production from lipopolysaccharide (LPS) stimulated NR8383 cells, a rat alveolar macrophage cell line, by adequate physicochemical properties and mannose receptor-mediated cellular uptake. Intravenous injection of Man-S-alpha-CDE (G3, DSM4)/sip65 complex extended the survival rate of LPS-induced fulminant hepatitis model mice. In addition, intravenous administration of Man-S-alpha-CDE (G3, DSM4)/sip65 complex had the potential to induce the in vivo RNAi effect by significant suppression of mRNA expression of NF-kappaB p65 and inflammatory cytokines in the liver of fulminant hepatitis model mice induced by LPS/d-galactosamine (d-Gal) without any significant side effects. Also, the serum levels of enzymes were significantly attenuated by injection of Man-S-alpha-CDE (G3, DSM4)/sip65 complex in fulminant hepatitis model mice. Collectively, these results suggest that Man-S-alpha-CDE (G3, DSM4) has the potential as a novel APC-selective sip65 carrier for the treatment of LPS/d-Gal-induced fulminant hepatitis in mice. PMID- 26270771 TI - In Vitro Effects of Anti-Glaucomatous Eye Drops on Platelet-Activating Factor and its Metabolism. AB - PURPOSE: The purpose of this study is to determine the effect of various commonly used antiglaucoma eye drops on inflammatory mediators such as the platelet activating factor (PAF). METHODS: Various intraocular pressure (IOP) lowering drops were tested to examine their inhibitory effect on PAF. Multiple eye drops were tested in washed rabbit platelets (WRPs) in order to determine the interaction between these eye drops and the inhibition of PAF in the PAF-induced platelet aggregation model. In addition, we examined the eyedrops' effect on PAF metabolism, through in vitro analysis on PAF basic metabolic enzymes (PAF-CPT, lyso PAF-AT, and PAF-AH). RESULTS: Latanoprost (Xalatan) was found to be the most potent in inhibiting PAF, suggesting that it is the most effective in decreasing IOP amongst the eye drops tested. Conversely, dorzolamide hydrochloride-timolol (Cosopt) exhibited the least anti-PAF action. CONCLUSIONS: This is the first study examine the relationship between PAF activity and glaucoma medication. Potency in PAF inhibition may be related to drop efficacy. PMID- 26270772 TI - Sex difference in the risk of recurrent venous thrombosis: a detailed analysis in four European cohorts. AB - BACKGROUND: Previous analyses reported a higher risk of recurrent venous thrombosis in men than women. OBJECTIVES: We aimed to assess the risk of recurrence in men compared with women whilst taking female reproductive risk factors (oral contraception, postmenopausal hormone therapy and pregnancy) into account. In addition, we hypothesized that the sex difference in venous thrombosis was related to F9 Malmo, an X-linked prothrombotic factor. METHODS: In four pooled European cohorts (CARROT study, Glasgow, UK; CVTE study, Cambridge, UK; AUREC study, Vienna, Austria; and LETS follow-up study, Leiden, the Netherlands), the risk of recurrent venous thrombosis was calculated in men, women with reproductive risk factors and women without reproductive risk factors at the time of their first venous thrombosis. F9 Malmo was genotyped and carriers and non-carriers contrasted. RESULTS: In total, 2185 patients with a first venous thrombosis, 1043 men and 1142 women, were included. Overall, men had a 2.8-fold (95% confidence interval [CI], 2.2-3.4) higher risk of recurrent venous thrombosis than women. This risk was 5.2-fold (95% CI, 3.5-7.7) higher in men than in women with reproductive risk factors, and 2.3-fold (95% CI, 1.7-3.2) higher in men than in women without reproductive risk factors. No difference in risk of recurrence was found for carriers vs. non-carriers of F9 Malmo. CONCLUSION: Men experienced a recurrent venous thrombosis twice as often as women without reproductive risk factors. These findings indicate that men have a higher intrinsic risk of venous thrombosis than women, which is partly masked by female reproductive risk factors. The sex difference cannot be explained by F9 Malmo. PMID- 26270774 TI - Synthesis, Structure, and Rigid Unit Mode-like Anisotropic Thermal Expansion of BaIr2In9. AB - This Article reports the synthesis of large single crystals of BaIr2In9 using In flux and their characterization by variable-temperature single-crystal and synchrotron powder X-ray diffraction, resistivity, and magnetization measurements. The title compound adopts the BaFe2Al9-type structure in the space group P6/mmm with room temperature unit cell parameters a = 8.8548(6) A and c = 4.2696(4) A. BaIr2In9 exhibits anisotropic thermal expansion behavior with linear expansion along the c axis more than 3 times larger than expansion in the ab plane between 90 and 400 K. This anisotropic expansion originates from a rigid unit mode-like mechanism similar to the mechanism of zero and negative thermal expansion observed in many anomalous thermal expansion materials such as ZrW2O8 and ScF3. PMID- 26270773 TI - Introducing demographic corrections for the 10/36 Spatial Recall Test. AB - OBJECTIVE: The 10/36 Spatial Recall Test is a measure of visuospatial memory and has been recommended for inclusion when administering a brief cognitive assessment to patients with multiple sclerosis by multiple groups. However, a notable limitation of the measure includes a lack of normative data with demographic corrections. Thus, the primary objective of the current study was to examine demographic influences on the 10/36 Spatial Recall Test and to introduce demographically corrected normative data for the instrument. METHODS: Data were collected from 116 participants over the age of 50 years. All study participants were free of any neurologic disease or disorder and classified as cognitively intact by a consensus conference team that was comprised of neurologists and neuropsychologists. All study participants were administered a neuropsychological evaluation that included the 10/36 Spatial Recall Test Version A at the baseline visit. RESULTS: 10/36 Spatial Recall Test scores were affected by age, education, and race. Gender effects were not observed. Given these effects, regression equations were used to correct for the effects of demographic variables. The z scores obtained from these corrections were not significantly influenced by demographical variables. CONCLUSION: The demographic corrections introduced in this paper offer the possibility to enhance the clinical utility of the 10/36 Spatial Recall Test. PMID- 26270775 TI - Serial Ultrasound Monitoring for Early Recognition of Asparaginase Associated Pancreatitis in Children With Acute Lymphoblastic Leukemia. AB - BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer in children and L-asparaginase is an essential component of the treatment. Cessation of L-asparaginase decreases event free survival. Acute pancreatitis is the toxicity that most commonly results in cessation of L-asparaginase. We tested whether serial ultrasound examinations could predict asparaginase-associated pancreatitis (AAP). METHODS: Children (aged 1.0-17.9 years) with childhood ALL treated at the University Hospital Rigshopitalet, Copenhagen, according to the standard or intermediate risk arms of the NOPHO ALL2008 protocol, with PEG asparaginase of 2 or 6 week intervals, for 30 weeks had their pancreas monitored using serial ultrasound in order to detect early signs of inflammation. RESULTS: Nineteen of 31 eligible patients were included. Three of the included patients developed AAP. None of the patients, including the three patients that developed AAP, had signs of inflammatory edema or pancreas enzymes above three times the upper normal limit prior to AAP. CONCLUSION: We found no signs of inflammatory edema within the pancreas on ultrasound during treatment with PEG-asparginase in our cohort prior to development of AAP or in patients that did not develop AAP. PMID- 26270776 TI - Laboratory automation: letting scientists focus on science. PMID- 26270777 TI - Scientific or regulated validation: a tiered approach? Meeting report from a joint EBF/DVDMDG workshop. AB - Tiered approach is rapidly gaining interest in the regulated bioanalytical community. Alternative approaches to the workflows as proposed in the regulatory Guidance (US FDA, EMA) are being used in discovery and early drug development, but with a growing array of assay types and studies requiring bioanalytical support in early drug development, the bioanalytical community is discussing how to bring best value to support these studies. Recently, international industry groups like European Bioanalysis Forum and Global Bioanalysis Consortium have discussed and published on the opportunity and need to include tiered approach more systematically in the early drug development support. On the back of these discussions, the Delaware Valley Drug Metabolism Discussion Group together with the European Bioanalysis Forum organized a meeting in Langhorne (PA, USA) to discuss the hurdles and added value of tiered approach with stakeholders from the Bioanalysis, quality assurance and PK community. The discussions focused on proposing scientific validation for studies where there is currently a mixed use of regulatory and tiered approach workflows. The meeting was well attended and the presentations and panel discussions contributed to a better understanding of what the industry is proposing as future practice. PMID- 26270779 TI - The relation of the number of hydrogen-bond acceptors with recoveries of immunosuppressants in DBS analysis. AB - BACKGROUND: We investigated the influence of the number of hydrogen-bond acceptors on the recovery of immunosuppressant drugs and their structural analogs. This hypothesis was tested by evaluation of the extraction recoveries of tacrolimus, ascomycin, sirolimus, everolimus and temsirolimus with 12, 12, 13, 14 and 16 hydrogen-bond acceptors, respectively. RESULTS: With an increasing number of hydrogen-bond acceptors of sirolimus, everolimus and temsirolimus, a decrease in recoveries was found while ascomycin showed recoveries corresponding to those of tacrolimus. CONCLUSION: This study showed that the number of hydrogen-bond acceptors of the analyte of interest may influence the recoveries in dried blood spot analysis and is a relevant factor to be investigated during method development and validation. PMID- 26270778 TI - 6th Japan Bioanalysis Forum Symposium: challenge of regulated bioanalysis. AB - Biomarker measurement and LC-MS analysis of large molecule pharmaceuticals (LM MS) are becoming increasingly important in pharmaceutical development, although they are not included in the existing bioanalytical method validation guidelines in Japan. The 6th Japan Bioanalysis Forum symposium presented challenges regarding biomarkers and LM-MS, as well as the current circumstances for regulated bioanalysis, by inviting speakers from Japan, the USA, European Union and Asia-pacific. Japan Bioanalysis Forum discussion groups also presented their outcomes and openly discussed these with the attendees - over 200 dedicated individuals from industry, regulatory agencies and academia. The symposium successfully reinforced the idea that fit-for-purpose approaches are necessary, and that science should drive any judgments and actions throughout drug development. PMID- 26270780 TI - Polymer-nanoparticles composites in bioanalytical sample preparation. AB - The term composite refers to a class of synthetic materials made from different constituents which exhibit final properties which are different from those of the individual components. Composites have been extensively used in the sample treatment context as sorbents since the resulting solid presents better extraction efficiency. In this realm, polymeric nanocomposites are raised as a powerful alternative. They can be tailored-synthesized for selectivity enhancement or include a magnetic core to simplify the extraction/elution process. This review article points out the relevance of such nanomaterials in bioanalysis. Several synergic combinations of nanoparticles (magnetic, carbon based) as well as polymeric coatings (conventional, conductive or molecularly imprinted) are commented on. Finally, the potential of biopolymers in the microextraction field is briefly highlighted. PMID- 26270781 TI - Linearity of chromatographic systems in drug analysis part I: theory of nonlinearity and quantification of curvature. AB - Traditional approaches to the assessment of the linearity of chromatographic assays initially assume that the concentration-response relationship is linear and only deemed to be nonlinear if certain parameters lie outside pre-set acceptance criteria. A different approach is described in that the a priori assumption is made that the assay does have some curvature that can be described by fitting a nonlinear regression curve. Any nonlinearity can be quantified from the curvature terms of the resultant regression coefficients. The success of this alternative approach is dependent upon the appropriate choice of nonlinear regression to accurately describe concentration versus response relationship of the assay. PMID- 26270782 TI - Linearity of chromatographic systems in drug analysis part II: a Monte Carlo justification for the use of nonlinear regressions. AB - In Part I of this series of communications an alternative approach was outlined to quantify the deviation from linearity by estimation of the change in true sensitivity of several mathematically defined concentration-response relationships. In this paper, Monte Carlo techniques were used to compare the strengths and limitations of linear and nonlinear regressions in assay calibrations. Nonlinear regressions can define a calibration curve as efficiently as a linear regression. Provided that the nonlinear regression is matched to the actual nonlinear concentration-response relationship, the use of nonlinear regressions can improve the accuracy of the assay and increase the percentage of calibrations meeting acceptance criteria. PMID- 26270783 TI - Linearity of chromatographic systems in drug analysis part III: examples of nonlinear drug assays. AB - Chromatography-based drug assays are generally considered to be linear, provided that the back calculated concentrations of 75% of the calibrators are within +/ 15% of their target values. Data meeting this criterion are not usually subject to further examination in order to evaluate the extent of any nonlinearity and whether use of a nonlinear calibration function would improve the accuracy. Examples of nonlinear behavior are presented for several chromatographic systems and most are best described by the nonlinear equation y = a + bx + cxln(x). A more critical evaluation of linearity, as presented herein, can lead to the identification of nonlinear behavior and an improvement in accuracy by use of a nonlinear calibration regression. PMID- 26270785 TI - Determination of lipoic acid in biological samples. AB - alpha-Lipoic acid (LA) is a unique antioxidant that is not only effective in affording protection against oxidative stress but also plays an essential role in metabolic processes of all living organisms. Therefore, the determination of LA and its metabolites content is crucial for understanding their physiological and pathophysiological functions. Most of the recently developed methods for the detection and determination of LA and its metabolites in various biological samples have focused on sample preparation procedures involving but not limited to sampling, extraction and storage. The main goal of this review is to summarize and critically evaluate the current state of the art of analytical procedures applied to the determination of LA and related compounds in biological samples. PMID- 26270784 TI - Strategies to compare clinical antitherapeutic antibody data when changing assay platforms: a case study. AB - Zhihua Julia Qiu has over 20 years post PhD experience in academic institutes, pharmaceutical industry and biotechnology startup settings; focused on novel therapeutics discovery and development and diagnostic tools. She is currently a Scientist in the Bioanalytical Sciences department at Genentech; responsible for developing, evaluating and implementing Bioanalytical strategy to support protein therapeutics development. That includes assay development and validation to evaluate PK, antitherapeutic antibodies as well as biomarkers in both nonclinical and clinical studies for Immunology and Oncology indications. In addition, she has led the evaluation of multiple novel technology platforms and transitioning assay platform to enable continuous support for the development of protein therapeutics and antibody-drug conjugates. PMID- 26270786 TI - Nano-LC in proteomics: recent advances and approaches. AB - In proteomics, nano-LC is arguably the most common tool for separating peptides/proteins prior to MS. The main advantage of nano-LC is enhanced sensitivity, as compounds enter the MS in more concentrated bands. This is particularly relevant for determining low abundant compounds in limited samples. Nano-LC columns can produce peak capacities of 1000 or more, and very narrow columns can be used to perform proteomics of 1000 cells or less. Also, nano-LC can be coupled with online add-ons such as selective trap columns or enzymatic reactors, for faster and more automated analysis. Nano-LC is today an established tool for research laboratories; but can nano-LC-based systems soon be ready for more routine settings, such as in clinics? PMID- 26270787 TI - Comment on "UV Disinfection Induces a VBNC State in Escherichia coli and Pseudomonas aeruginosa". PMID- 26270790 TI - Streptococcal Serology: Secrets for the Specialist. PMID- 26270789 TI - Extracellular Stiffness Modulates the Expression of Functional Proteins and Growth Factors in Endothelial Cells. AB - Angiogenesis, the formation of blood vessels from pre-existing ones, is of vital importance during the early stages of bone healing. Extracellular stiffness plays an important role in regulating endothelial cell behavior and angiogenesis, but how this mechanical cue affects proliferation kinetics, gene regulation, and the expression of proteins implicated in angiogenesis and bone regeneration remains unclear. Using collagen-coated polyacrylamide (PAAm) hydrogels, human umbilical vein endothelial cells (HUVECs) are exposed to an environment that mimics the elastic properties of collagenous bone, and cellular proliferation and gene and protein expressions are assessed. The proliferation and gene expression of HUVECs are not differentially affected by culture on 3 or 30 kPa PAAm hydrogels, henceforth referred to as low and high stiffness gels, respectively. Although the proliferation and gene transcript levels remain unchanged, significant differences are found in the expressions of functional proteins and growth factors implicated both in the angiogenic and osteogenic processes. The down regulation of the vascular endothelial growth factor receptor-2 protein with concomitant over-expression of caveolin-1, wingless-type 2, bone morphogenic protein 2, and basic fibroblast growth factor on the high stiffness PAAm hydrogel suggests that rigidity has a pro-angiogenic effect with inherent benefits for bone regeneration. PMID- 26270788 TI - Society for Endocrinology UK guidance on the initial evaluation of an infant or an adolescent with a suspected disorder of sex development (Revised 2015). AB - It is paramount that any child or adolescent with a suspected disorder of sex development (DSD) is assessed by an experienced clinician with adequate knowledge about the range of conditions associated with DSD. If there is any doubt, the case should be discussed with the regional DSD team. In most cases, particularly in the case of the newborn, the paediatric endocrinologist within the regional team acts commonly as the first point of contact. This clinician should be part of a multidisciplinary team experienced in management of DSD and should ensure that the affected person and parents have access to specialist psychological support and that their information needs are comprehensively addressed. The underlying pathophysiology of DSD and the strengths and weaknesses of the tests that can be performed should be discussed with the parents and affected young person and tests undertaken in a timely fashion. Finally, in the field of rare conditions, it is imperative that the clinician shares the experience with others through national and international clinical and research collaboration. PMID- 26270791 TI - Black Phosphorus Terahertz Photodetectors. AB - The first room-temperature terahertz (THz)-frequency nanodetector exploiting a 10 nm thick flake of exfoliated crystalline black phosphorus as an active channel of a field-effect transistor, is devised. By engineering and embedding planar THz antennas for efficient light harvesting, the first technological demonstration of a phosphorus-based active THz device is described. PMID- 26270792 TI - Molecular orbital theory of the electronic structure of organic compounds. I. Substituent effects and dipole moments. PMID- 26270793 TI - Mass of the Anterior Mandible. PMID- 26270794 TI - Correction: Longitudinal Study of the Decline in Renal Function in Healthy Subjects. PMID- 26270795 TI - Feasibility of Remote Ischemic Peri-conditioning during Air Medical Transport of STEMI Patients. AB - Remote ischemic peri-conditioning (RIPC) has gained interest as a means of reducing ischemic injury in patients with acute ST-elevation myocardial infarction (STEMI) who are undergoing emergent primary percutaneous coronary intervention (pPCI). We aimed to evaluate the feasibility, process, and patient related factors related to the delivery of RIPC during air medical transport of STEMI patients to tertiary pPCI centers. We performed a retrospective review of procedural outcomes of a cohort of STEMI patients who received RIPC as part of a clinical protocol in a multi-state air medical service over 16 months (March 2013 to June 2014). Eligible patients were transported to two tertiary PCI centers and received up to four cycles of RIPC by inflating a blood pressure cuff on an upper arm to 200 mmHg for 5 minutes and subsequently deflating the cuff for 5 minutes. Data regarding feasibility, process variables, patient comfort, and occurrence of hypotension were obtained from prehospital records and prospectively completed quality improvement surveys. The primary outcome was whether at least 3 cycles of RIPC were completed by air medical transport crews prior to pPCI. Secondary outcomes included the number of cycles completed prior to pPCI, time spent with the patient prior to transport (bedside time), patient discomfort level, and incidence of hypotension (systolic blood pressure <90 mmHg) during the procedure. RIPC was initiated in 99 patients (91 interfacility, 8 scene transports) and 83 (83.3%) received 3 or 4 cycles of RIPC, delivered over 25-35 minutes. Median bedside time for interfacility transfers was 8 minutes (IQR 7, 10). More than half of patients reported no pain related to the procedure (N = 53, 53.3%), whereas 5 (5.1%) patients reported discomfort greater than 5 out of 10. Two patients developed hypotension while receiving RIPC and both had experienced hypotension prior to initiation of RIPC. RIPC is feasible and safe to implement for STEMI patients undergoing air medical transport for pPCI, without occurrence of prolonged bedside times. The incidence of excessive RIPC-related discomfort or hemodynamic instability is rare. STEMI patients requiring on average >30 minutes transport for pPCI may be the ideal group for RIPC utilization. PMID- 26270796 TI - Analysis of the synthetic house-tree-person drawing test for developmental disorder. AB - BACKGROUND: Some patients cannot draw three subjects on the same page during the synthetic house-tree-person drawing test (S-HTP). We call this phenomenon "no synthetic sign". The aim of this study was to clarify the pathological meaning of no synthetic sign and investigate its use for the early detection of developmental disorders at a pediatric primary care center. METHODS: We administered the S-HTP to 283 people who consulted the child psychosomatic medical clinic of Okayama University Hospital in 2007-2012. We diagnosed developmental disability based on DSM-IV-TR criteria and compared findings between the different diagnostic groups. RESULTS: A total of 241 patients completed the S-HTP (S-HTP group) and 22 patients were not able to complete the S HTP, but did complete the HTP (an original version of the S-HTP) or tree test (HTP group). Significantly more people in the HTP group had autism spectrum disorder (ASD) compared with the S-HTP group. Full-scale intelligence quotient was significantly lower in the HTP group compared with the S-HTP group. CONCLUSIONS: There were two types of patients with no synthetic sign. The first involved patients with a suspected mental age younger than 5 years 11 months. The second type consisted of patients with ASD. Although drawing ability reflects multiple domains, it may help in early identification of children with developmental problems and facilitate earlier initiation of interventions. PMID- 26270797 TI - Amisulpride Augmentation in Acute Catatonia. AB - Benzodiazepines are the first-line treatment of catatonia, but a substantial number of patients do not respond to them. Amisulpride is one of the atypical antipsychotic that has been effective for negative symptoms of schizophrenia. We examined the effect of augmentation of oral low doses of amisulpride with lorazepam on resolution of catatonic symptoms. Fifteen patients with catatonia were treated with a combination of oral lorazepam (2-4 mg) with amisulpride (100 mg). Catatonic symptoms were rated using the Bush Francis Catatonia Rating Scale at the baseline and daily thereafter. There was complete resolution of catatonic symptoms on the third day in all patients. There was significant reduction of the total Bush Francis Catatonia Rating Scale score over time (F = 181.38, P < 0.001) with a strong effect size (partial eta = 0.96). Augmentation of lorazepam with low-dose amisulpride can be a reliable strategy for management of catatonia. PMID- 26270798 TI - Long (>12 Months) and Short (<6 Months) Versus Standard Duration of Dual Antiplatelet Therapy After Coronary Stenting: A Systematic Review and Meta Analysis. AB - Dual antiplatelet therapy (DAPT) is recommended for 6-12 months after drug eluting stent (DES) implantation to prevent ischemic events and late stent thrombosis. The optimal duration of DAPT has not been established. We performed a meta-analysis of the comparative effects of short and long versus standard duration DAPT duration on adverse cardiovascular and major bleeding. We conducted an EMBASE and MEDLINE search for studies in which patients were randomized to treatment with a different duration of DAPT. We included studies that provided data on DES selection, DAPT regimen and duration, and incidence of the selected endpoints at the end of the follow-up period. We identified 5 prospective randomized studies comparing short versus standard duration DAPT and 3 comparing long versus standard duration DAPT with a total of 28,343 patients. Short-term DAPT has similar incidence of stent thrombosis, MI, and death compared to standard duration DAPT, whereas major bleeding was significantly lower in short duration DAPT. Long-term DAPT was associated with lower rates of stent thrombosis and MI but significantly increased major bleeding and all-cause mortality compared to standard duration DAPT. In this meta-analysis of prospective controlled studies we found that short duration DAPT is safer and as effective as standard duration DAPT in patients with second-generation DES. Extended DAPT is associated with less ischemic events at the expense of high bleeding and mortality rates. PMID- 26270799 TI - Mycobacterium Avium Complex Septic Arthritis in a Patient Treated by Infliximab. AB - Infliximab is one of the TNF-alpha inhibitors, a class of medications that made a revolution in treatment of rheumatic diseases especially rheumatoid arthritis. The activation of tuberculosis and atypical mycobacterial infections has been described in the setting of TNF-alpha inhibitor therapy, but septic arthritis relating to this treatment has not yet been reported in previous literature. We describe a 50-year-old woman with dermatomyositis who developed Mycobacterium Avium Complex septic arthritis, while being treated with infliximab for active skin disease. This case highlights an important complication related to therapy with TNF-alpha inhibitors. PMID- 26270800 TI - Unusual Bleeding Due to Riociguat Use in a Patient With Chronic Thromboembolic Pulmonary Hypertension. AB - Riociguat is a new drug prescribed to patients with pulmonary hypertension that reduces the pressure in pulmonary artery by vasodilation. This drug like many other drugs has several side effects, some of which can be serious such as bleeding. Riociguat causes vaginal bleeding by increasing endometrial thickness and blood flow to the endometrium, therefore, should be used with care especially for patients who have history of dysfunctional uterine bleeding. In this case report, we present a 27-year-old female patient with chronic thromboembolic pulmonary hypertension and dysfunctional uterine bleeding presented with severe vaginal bleeding under riociguat treatment. PMID- 26270801 TI - Edible Flowers: A Rich Source of Phytochemicals with Antioxidant and Hypoglycemic Properties. AB - Edible flowers are receiving renewed interest as rich sources of bioactive compounds. Ethanol extracts of eight edible flowers were phytochemically characterized and investigated for their bioactivity. Rutin, quercetin, luteolin, kaempferol, and myricetin were selected as standards and quantified by HPLC. The fatty acid profile was analyzed by GC and GC-MS. Antioxidant properties were evaluated by using different in vitro tests. The hypoglycemic effects were investigated via the inhibition of alpha-amylase and alpha-glucosidase. Sambucus nigra exhibited the highest radical-scavenging activity (IC50 of 1.4 MUg/mL), followed by Hedysarum coronarium (IC50 of 1.6 MUg/mL). Both species contained high quercetin and rutin contents. S. nigra extract exerted the highest activity in preventing lipid oxidation. Malva sylvestris extract inhibited both alpha amylase and alpha-glucosidase with IC50 values of 7.8 and 11.3 MUg/mL, respectively. These findings support the consumption of edible flowers as functional foods and their use as sources of natural antioxidants by the food industry. PMID- 26270802 TI - The first case of a small supernumerary marker chromosome derived from chromosome 10 in an adult woman with an apparently normal phenotype. AB - Small supernumerary marker chromosomes (sSMCs) originating from chromosome 10 are rare. A limited number of cases are documented. We report a new diagnosis of a mosaic sSMC (10) in a normal female who asked for genetic evaluation before undergoing controlled ovarian hyperstimulation, in vitro fertilization, and embryo transfer. Chromosome preparations from peripheral lymphocyte cultures were performed according to standard procedures. QFQ-banded chromosomes confirmed the presence of an sSMC: 47,XX,+mar[49]/46,XX[51]. FISH and array CGH analysis showed that the sSMC consisted of chromosome 10 with a gain of the 10p11.1p11.21 (2.5 Mb) chromosomal region. The presence of sSMC (10) was also confirmed in the patient's mother and sister. It did not appear to affect the phenotype of the women who were phenotypically normal and healthy, and at the time of writing the woman became pregnant naturally. Phenotypes associated with an sSMC vary from normal to severely abnormal. It has been shown that variations in the chromosomal region of sSMCs result in observable differences in clinical outcome. The phenotypical consequences of sSMCs are difficult to predict because of differences in euchromatic DNA content, chromosomal origin, and varying degrees of mosaicism. Therefore, the continued investigation of a larger number of sSMC cases, in particular those originating from chromosome 10 that are the infrequently encountered and characterized, and a better understanding of the genetic content is important in order to improve the delineation of karyotype phenotype correlation, contributing to a more informed prenatal counseling or prognosis. PMID- 26270804 TI - Oxidation of Gas-Phase SO2 on the Surfaces of Acidic Microdroplets: Implications for Sulfate and Sulfate Radical Anion Formation in the Atmospheric Liquid Phase. AB - The oxidation of SO2(g) on the interfacial layers of microdroplet surfaces was investigated using a spray-chamber reactor coupled to an electrospray ionization mass spectrometer. Four major ions, HSO3(-), SO3(*-), SO4(*-) and HSO4(-), were observed as the SO2(g)/N2(g) gas-mixture was passed through a suspended microdroplet flow, where the residence time in the dynamic reaction zone was limited to a few hundred microseconds. The relatively high signal intensities of SO3(*-), SO4(*-), and HSO4(-) compared to those of HSO3(-) as observed at pH < 3 without addition of oxidants other than oxygen suggests an efficient oxidation pathway via sulfite and sulfate radical anions on droplets possibly via the direct interfacial electron transfer from HSO3(-) to O2. The concentrations of HSO3(-) in the aqueous aerosol as a function of pH were controlled by the deprotonation of hydrated sulfur dioxide, SO2.H2O, which is also affected by the pH dependent uptake coefficient. When H2O2(g) was introduced into the spray chamber simultaneously with SO2(g), HSO3(-) is rapidly oxidized to form bisulfate in the pH range of 3 to 5. Conversion to sulfate was less at pH < 3 due to relatively low HSO3(-) concentration caused by the fast interfacial reactions. The rapid oxidation of SO2(g) on the acidic microdroplets was estimated as 1.5 * 10(6) [S(IV)] (M s(-1)) at pH <= 3. In the presence of acidic aerosols, this oxidation rate is approximately 2 orders of magnitude higher than the rate of oxidation with H2O2(g) at a typical atmospheric H2O2(g) concentration of 1 ppb. This finding highlights the relative importance of the acidic surfaces for SO2 oxidation in the atmosphere. Surface chemical reactions on aquated aerosol surfaces, as observed in this study, are overlooked in most atmospheric chemistry models. These reaction pathways may contribute to the rapid production of sulfate aerosols that is often observed in regions impacted by acidic haze aerosol such as Beijing and other megacities around the world. PMID- 26270803 TI - Nocarbenzoxazoles A-G, Benzoxazoles Produced by Halophilic Nocardiopsis lucentensis DSM 44048. AB - Seven new benzoxazole derivatives, nocarbenzoxazoles A-G (1-7), were isolated from the halophilic strain Nocardiopsis lucentensis DSM 44048. Their structures were elucidated on the basis of 1D and 2D NMR spectroscopic data, HRESIMS, and X ray single-crystal diffraction. The isolated compounds were assayed for their cytotoxicity against a panel of human tumor cell lines (HepG2, MDA-MB-231, MDA-MB 435, HeLa, and PC3). Compounds 1-6 were found to have modest or no activity. Compound 7 showed selective activity against HepG2 and HeLa with IC50 values of 3 and 1 MUM, respectively. PMID- 26270805 TI - Protein Synthesis in E. coli: Dependence of Codon-Specific Elongation on tRNA Concentration and Codon Usage. AB - To synthesize a protein, a ribosome moves along a messenger RNA (mRNA), reads it codon by codon, and takes up the corresponding ternary complexes which consist of aminoacylated transfer RNAs (aa-tRNAs), elongation factor Tu (EF-Tu), and GTP. During this process of translation elongation, the ribosome proceeds with a codon specific rate. Here, we present a general theoretical framework to calculate codon-specific elongation rates and error frequencies based on tRNA concentrations and codon usages. Our theory takes three important aspects of in vivo translation elongation into account. First, non-cognate, near-cognate and cognate ternary complexes compete for the binding sites on the ribosomes. Second, the corresponding binding rates are determined by the concentrations of free ternary complexes, which must be distinguished from the total tRNA concentrations as measured in vivo. Third, for each tRNA species, the difference between total tRNA and ternary complex concentration depends on the codon usages of the corresponding cognate and near-cognate codons. Furthermore, we apply our theory to two alternative pathways for tRNA release from the ribosomal E site and show how the mechanism of tRNA release influences the concentrations of free ternary complexes and thus the codon-specific elongation rates. Using a recently introduced method to determine kinetic rates of in-vivo translation from in-vitro data, we compute elongation rates for all codons in Escherichia coli. We show that for some tRNA species only a few tRNA molecules are part of ternary complexes and, thus, available for the translating ribosomes. In addition, we find that codon-specific elongation rates strongly depend on the overall codon usage in the cell, which could be altered experimentally by overexpression of individual genes. PMID- 26270807 TI - Role of splenic monocytes in atherosclerosis. AB - PURPOSE OF REVIEW: This review relates recent findings that highlight the role of the spleen as an active donor of monocytes during inflammation, with a special focus on atherosclerosis. RECENT FINDINGS: The contribution of hypercholesterolemia and monocytes/macrophages to atherosclerotic lesion formation is undisputable. The origin of plaque macrophages is, however, still a subject of debate as to whether they derive from local amplification of (resident) macrophages or from continuous recruitment and differentiation of monocytes. Recently, the spleen has emerged as an important reservoir of monocytes that contributes to lesion growth. The regulation of monocyte mobilization from the splenic compartment has, therefore, raised a keen interest in understanding the cellular and molecular mechanisms involved in this process. SUMMARY: Impaired regulation of cholesterol metabolism increases the proliferation of hematopoietic stem and progenitor cells in both the bone marrow and the spleen. Recent findings identified the implication of angiotensin II, red pulp macrophages and B-lymphocytes as partners of monocyte expansion in, and mobilization from the spleen. Future studies will help in understanding the mechanisms of monocyte mobilization and its precise roles in atherosclerosis, and whether modulation of the splenic components may become a promising future direction in the prevention and treatment of cardiovascular diseases. PMID- 26270806 TI - Evidence for pollinator cost and farming benefits of neonicotinoid seed coatings on oilseed rape. AB - Chronic exposure to neonicotinoid insecticides has been linked to reduced survival of pollinating insects at both the individual and colony level, but so far only experimentally. Analyses of large-scale datasets to investigate the real world links between the use of neonicotinoids and pollinator mortality are lacking. Moreover, the impacts of neonicotinoid seed coatings in reducing subsequent applications of foliar insecticide sprays and increasing crop yield are not known, despite the supposed benefits of this practice driving widespread use. Here, we combine large-scale pesticide usage and yield observations from oilseed rape with those detailing honey bee colony losses over an 11 year period, and reveal a correlation between honey bee colony losses and national-scale imidacloprid (a neonicotinoid) usage patterns across England and Wales. We also provide the first evidence that farmers who use neonicotinoid seed coatings reduce the number of subsequent applications of foliar insecticide sprays and may derive an economic return. Our results inform the societal discussion on the pollinator costs and farming benefits of prophylactic neonicotinoid usage on a mass flowering crop. PMID- 26270809 TI - Recent developments in modulating atherogenic lipoproteins. AB - PURPOSE OF REVIEW: Randomized clinical trials have assessed the effects of several classes of drugs on plasma cholesterol levels in patients with coronary artery disease. Agents including niacin, fibrates and statins significantly lower LDL-cholesterol, but tolerance issues and undesirable side-effects are common. Residual risk may also be present in patients with persistently low HDL cholesterol despite a reduction in LDL-cholesterol. Recent trials of drugs that increase circulating HDL-cholesterol have also been disappointing. RECENT FINDINGS: Ongoing efforts target the development of new pharmacotherapies to reduce circulating levels of atherogenic lipoproteins. The goal of this review is to discuss recent advances in the treatment of coronary artery disease and other vascular diseases characterized by an increase in circulating atherogenic lipoproteins. These include the development of inhibitors of ATP citrate lyase and proprotein convertase subtilisin/kexin type 9. We also discuss recent developments in HDL therapy, including the clinical assessment of cholesteryl ester transfer protein inhibitors and apolipoprotein E mimetic peptides. SUMMARY: Several new classes of drug are undergoing clinical evaluation that show promise for atherogenic lipoprotein reduction in patients who are statin intolerant. PMID- 26270808 TI - Lysophospholipids in coronary artery and chronic ischemic heart disease. AB - PURPOSE OF REVIEW: The bioactive lysophospholipids, lysophosphatidic acid (LPA) and sphingosine 1 phosphate (S1P), have potent effects on blood and vascular cells. This review focuses their potential contributions to the development of atherosclerosis, acute complications such as acute myocardial infarction, and chronic ischemic cardiac damage. RECENT FINDINGS: Exciting recent developments have provided insight into the molecular underpinnings of LPA and S1P receptor signaling. New lines of evidence suggest roles for these pathways in the development of atherosclerosis. In experimental animal models, the production, signaling, and metabolism of LPA may be influenced by environmental factors in the diet that synergize to promote the progression of atherosclerotic vascular disease. This is supported by observations of human polymorphisms in the lysophospholipid-metabolizing enzyme PPAP2B, which are associated with risk of coronary artery disease and myocardial infarction. S1P signaling protects from myocardial damage that follows acute and chronic ischemia, both by direct effects on cardiomyocytes and through stem cell recruitment to ischemic tissue. SUMMARY: This review will suggest novel strategies to prevent the complications of coronary artery disease by targeting LPA production and signaling. Additionally, ways in which S1P signaling pathways may be harnessed to attenuate ischemia induced cardiac dysfunction will be explored. PMID- 26270810 TI - Cholesterol efflux capacity, macrophage reverse cholesterol transport and cardioprotective HDL. AB - PURPOSE OF REVIEW: Randomized clinical trials provide strong evidence that pharmacological elevation of HDL-cholesterol (HDL-C) fails to reduce cardiovascular disease (CVD) risk in statin-treated humans. It is thus critical to identify new metrics that capture HDL's cardioprotective effects. RECENT FINDINGS: We review recent evidence that HDL's cholesterol efflux capacity is a strong inverse predictor of incident and prevalent CVD in humans. In light of those findings, we assess the proposal that impaired macrophage cholesterol efflux to HDL contributes to disease risk. We also discuss recent studies implicating small HDL particles in cholesterol efflux from macrophages. SUMMARY: These observations lay the foundation for a new approach to understanding mechanistically how HDL's functional properties help reduce CVD risk. PMID- 26270811 TI - Immune-mediated and lipid-mediated platelet function in atherosclerosis. AB - PURPOSE OF REVIEW: Cardiovascular disease (CVD) is the leading cause of death and morbidity worldwide. Detailed knowledge of the mechanisms of atherosclerosis, the main underlying disease of CVD, will enable improved preventive and therapeutic options, thus potentially limiting the burden of vascular disease in aging societies. A large body of evidence illustrates the contribution of platelets to processes beyond their traditionally recognized role as mediators in thrombosis and hemostasis. Recent advances in molecular biology help to understand the complexity of atherosclerosis. RECENT FINDINGS: This article outlines the role of platelets as modulators of immune responses in the context of atherosclerosis. It provides a short overview of interactions between platelets and endothelial cells or immune cells via direct cell contact or soluble factors during atherogenesis. By means of some well examined, exemplary pathways (e.g. CD40/CD40L dyad), this article will discuss recent discoveries in immune-related function of platelets. We also focus on the relationship between platelets and the lipid metabolism highlighting potential consequences to atherosclerosis and dyslipidemia. SUMMARY: A better understanding of the molecular mechanisms of platelet-related immune activity allows their utilization as powerful diagnostic tools or targets of therapeutic intervention. Those findings might help to develop new classes of drugs which may supplement or replace classical anticoagulants and help clinicians to tackle CVD more efficiently. PMID- 26270812 TI - Statistical, Morphometric, Anatomical Shape Model (Atlas) of Calcaneus. AB - The aim was to develop a morphometric and anatomically accurate atlas (statistical shape model) of calcaneus. The model is based on 18 left foot and 18 right foot computed tomography studies of 28 male individuals aged from 17 to 62 years, with no known foot pathology. A procedure for automatic atlas included extraction and identification of common features, averaging feature position, obtaining mean geometry, mathematical shape description and variability analysis. Expert manual assistance was included for the model to fulfil the accuracy sought by medical professionals. The proposed for the first time statistical shape model of the calcaneus could be of value in many orthopaedic applications including providing support in diagnosing pathological lesions, pre-operative planning, classification and treatment of calcaneus fractures as well as for the development of future implant procedures. PMID- 26270813 TI - Mu Opioid Splice Variant MOR-1K Contributes to the Development of Opioid-Induced Hyperalgesia. AB - BACKGROUND: A subset of the population receiving opioids for the treatment of acute and chronic clinical pain develops a paradoxical increase in pain sensitivity known as opioid-induced hyperalgesia. Given that opioid analgesics are one of few treatments available against clinical pain, it is critical to determine the key molecular mechanisms that drive opioid-induced hyperalgesia in order to reduce its prevalence. Recent evidence implicates a splice variant of the mu opioid receptor known as MOR-1K in the emergence of opioid-induced hyperalgesia. Results from human genetic association and cell signaling studies demonstrate that MOR-1K contributes to decreased opioid analgesic responses and produces increased cellular activity via Gs signaling. Here, we conducted the first study to directly test the role of MOR-1K in opioid-induced hyperalgesia. METHODS AND RESULTS: In order to examine the role of MOR-1K in opioid-induced hyperalgesia, we first assessed pain responses to mechanical and thermal stimuli prior to, during, and following chronic morphine administration. Results show that genetically diverse mouse strains (C57BL/6J, 129S6, and CXB7/ByJ) exhibited different morphine response profiles with corresponding changes in MOR-1K gene expression patterns. The 129S6 mice exhibited an analgesic response correlating to a measured decrease in MOR-1K gene expression levels, while CXB7/ByJ mice exhibited a hyperalgesic response correlating to a measured increase in MOR-1K gene expression levels. Furthermore, knockdown of MOR-1K in CXB7/ByJ mice via chronic intrathecal siRNA administration not only prevented the development of opioid-induced hyperalgesia, but also unmasked morphine analgesia. CONCLUSIONS: These findings suggest that MOR-1K is likely a necessary contributor to the development of opioid-induced hyperalgesia. With further research, MOR-1K could be exploited as a target for antagonists that reduce or prevent opioid-induced hyperalgesia. PMID- 26270814 TI - Comparison of Two Hybrid Models for Forecasting the Incidence of Hemorrhagic Fever with Renal Syndrome in Jiangsu Province, China. AB - BACKGROUND: Cases of hemorrhagic fever with renal syndrome (HFRS) are widely distributed in eastern Asia, especially in China, Russia, and Korea. It is proved to be a difficult task to eliminate HFRS completely because of the diverse animal reservoirs and effects of global warming. Reliable forecasting is useful for the prevention and control of HFRS. METHODS: Two hybrid models, one composed of nonlinear autoregressive neural network (NARNN) and autoregressive integrated moving average (ARIMA) the other composed of generalized regression neural network (GRNN) and ARIMA were constructed to predict the incidence of HFRS in the future one year. Performances of the two hybrid models were compared with ARIMA model. RESULTS: The ARIMA, ARIMA-NARNN ARIMA-GRNN model fitted and predicted the seasonal fluctuation well. Among the three models, the mean square error (MSE), mean absolute error (MAE) and mean absolute percentage error (MAPE) of ARIMA NARNN hybrid model was the lowest both in modeling stage and forecasting stage. As for the ARIMA-GRNN hybrid model, the MSE, MAE and MAPE of modeling performance and the MSE and MAE of forecasting performance were less than the ARIMA model, but the MAPE of forecasting performance did not improve. CONCLUSION: Developing and applying the ARIMA-NARNN hybrid model is an effective method to make us better understand the epidemic characteristics of HFRS and could be helpful to the prevention and control of HFRS. PMID- 26270815 TI - Phytochrome B Mediates the Regulation of Chlorophyll Biosynthesis through Transcriptional Regulation of ChlH and GUN4 in Rice Seedlings. AB - Accurate regulation of chlorophyll synthesis is crucial for chloroplast formation during the greening process in angiosperms. In this study, we examined the role of phytochrome B (phyB) in the regulation of chlorophyll synthesis in rice seedlings (Oryza sativa L.) through the characterization of a pale-green phenotype observed in the phyB mutant grown under continuous red light (Rc) irradiation. Our results show that the Rc-induced chlorophyll accumulation can be divided into two components--a phyB-dependent and a phyB-independent component, and that the pale-green phenotype is caused by the absence of the phyB-dependent component. To elucidate the role of the missing component we established an Rc induced greening experiment, the results of which revealed that several genes encoding proteins on the chlorophyll branch were repressed in the phyB mutant. Notable among them were ChlH and GUN4 genes, which encode subunit H and an activating factor of magnesium chelatase (Mg-chelatase), respectively, that were largely repressed in the mutant. Moreover, the kinetic profiles of chlorophyll precursors suggested that Mg-chelatase activity simultaneously decreased with the reduction in the transcript levels of ChlH and GUN4. These results suggest that phyB mediates the regulation of chlorophyll synthesis through transcriptional regulation of these two genes, whose products exert their action at the branching point of the chlorophyll biosynthesis pathway. Reduction of 5-aminolevulinic acid (5-ALA) synthesis could be detected in the mutant, but the kinetic profiles of chlorophyll precursors indicated that it was an event posterior to the reduction of the Mg-chelatase activity. It means that the repression of 5-ALA synthesis should not be a triggering event for the appearance of the pale-green phenotype. Instead, the repression of 5-ALA synthesis might be important for the subsequent stabilization of the pale-green phenotype for preventing excessive accumulation of hazardous chlorophyll precursors, which is an inevitable consequence of the reduction of Mg-chelatase activity. PMID- 26270816 TI - Mechanisms that Trigger a Good Health-Care Response to Intimate Partner Violence in Spain. Combining Realist Evaluation and Qualitative Comparative Analysis Approaches. AB - BACKGROUND: Health care professionals, especially those working in primary health care services, can play a key role in preventing and responding to intimate partner violence. However, there are huge variations in the way health care professionals and primary health care teams respond to intimate partner violence. In this study we tested a previously developed programme theory on 15 primary health care center teams located in four different Spanish regions: Murcia, C Valenciana, Castilla-Leon and Cantabria. The aim was to identify the key combinations of contextual factors and mechanisms that trigger a good primary health care center team response to intimate partner violence. METHODS: A multiple case-study design was used. Qualitative and quantitative information was collected from each of the 15 centers (cases). In order to handle the large amount of information without losing familiarity with each case, qualitative comparative analysis was undertaken. Conditions (context and mechanisms) and outcomes, were identified and assessed for each of the 15 cases, and solution formulae were calculated using qualitative comparative analysis software. RESULTS: The emerging programme theory highlighted the importance of the combination of each team's self-efficacy, perceived preparation and women centredness in generating a good team response to intimate partner violence. The use of the protocol and accumulated experience in primary health care were the most relevant contextual/intervention conditions to trigger a good response. However in order to achieve this, they must be combined with other conditions, such as an enabling team climate, having a champion social worker and having staff with training in intimate partner violence. CONCLUSIONS: Interventions to improve primary health care teams' response to intimate partner violence should focus on strengthening team's self-efficacy, perceived preparation and the implementation of a woman-centred approach. The use of the protocol combined with a large working experience in primary health care, and other factors such as training, a good team climate, and having a champion social worker on the team, also played a key role. Measures to sustain such interventions and promote these contextual factors should be encouraged. PMID- 26270817 TI - Influence of Dopaminergic Medication on Conditioned Pain Modulation in Parkinson's Disease Patients. AB - BACKGROUND: Pain is highly prevalent in patients with Parkinson's disease (PD), but little is known about the underlying pathophysiological mechanisms. The susceptibility to pain is known to depend on ascending and descending pathways. Because parts of the descending pain inhibitory system involve dopaminergic pathways, dysregulations in dopaminergic transmission might contribute to altered pain processing in PD. Deficits in endogenous pain inhibition can be assessed using conditioned pain modulation (CPM) paradigms. METHODS: Applying such a paradigm, we investigated i) whether CPM responses differ between PD patients and healthy controls, ii) whether they are influenced by dopaminergic medication and iii) whether there are effects of disease-specific factors. 25 patients with idiopathic PD and 30 healthy age- and gender-matched controls underwent an established CPM paradigm combining heat pain test stimuli at the forearm and the cold pressor task on the contralateral foot as the conditioning stimulus. PD patients were tested under dopaminergic medication and after at least 12 hours of medication withdrawal. RESULTS: No significant differences between CPM responses of PD patients and healthy controls or between PD patients "on" and "off" medication were found. These findings suggest (i) that CPM is insensitive to dopaminergic modulations and (ii) that PD is not related to general deficits in descending pain inhibition beyond the known age-related decline. However, at a trend level, we found differences between PD subtypes (akinetic-rigid, tremor dominant, mixed) with the strongest impairment of pain inhibition in the akinetic rigid subtype. CONCLUSIONS: There were no significant differences between CPM responses of patients compared to healthy controls or between patients "on" and "off" medication. Differences between PD subtypes at a trend level point towards different pathophysiological mechanisms underlying the three PD subtypes which warrant further investigation and potentially differential therapeutic strategies in the future. PMID- 26270819 TI - Are Human Intestinal Eukaryotes Beneficial or Commensals? PMID- 26270818 TI - Vitamin C Compound Mixtures Prevent Ozone-Induced Oxidative Damage in Human Keratinocytes as Initial Assessment of Pollution Protection. AB - INTRODUCTION: One of the main functions of cutaneous tissues is to protect our body from the outdoor insults. Ozone (O3) is among the most toxic stressors to which we are continuously exposed and because of its critical location, the skin is one of the most susceptible tissues to the oxidative damaging effect of O3. O3 is not able to penetrate the skin, and although it is not a radical per se, the damage is mainly a consequence of its ability to induce oxidative stress via the formation of lipid peroxidation products. AIM OF STUDY: In this study we investigated the protective effect of defined "antioxidant" mixtures against O3 induced oxidative stress damage in human keratinocytes and understand their underlying mechanism of action. RESULTS: Results showed that the mixtures tested were able to protect human keratinocytes from O3-induced cytotoxicity, inhibition of cellular proliferation, decrease the formation of HNE protein adducts, ROS, and carbonyls levels. Furthermore, we have observed the decreased activation of the redox sensitive transcription factor NF-kB, which is involved in transcribing pro-inflammatory cytokines and therefore constitutes one of the main players associated with O3 induced skin inflammation. Cells exposed to O3 demonstrated a dose dependent increase in p65 subunit nuclear expression as a marker of NF-kB activation, while pre-treatment with the mixtures abolished NF-kB nuclear translocation. In addition, a significant activation of Nrf2 in keratinocytes treated with the mixtures was also observed. CONCLUSION: Overall this study was able to demonstrate a protective effect of the tested compounds versus O3-induced cell damage in human keratinocytes. Pre-treatment with the tested compounds significantly reduced the oxidative damage induced by O3 exposure and this protective effect was correlated to the abolishment of NF-kB nuclear translocation, as well as activation of Nrf2 nuclear translocation activating the downstream defence enzymes involved in cellular detoxification process. PMID- 26270820 TI - Self-Orientation Modulates the Neural Correlates of Global and Local Processing. AB - Differences in self-orientation (or "self-construal") may affect how the visual environment is attended, but the neural and cultural mechanisms that drive this remain unclear. Behavioral studies have demonstrated that people from Western backgrounds with predominant individualistic values are perceptually biased towards local-level information; whereas people from non-Western backgrounds that support collectivist values are preferentially focused on contextual and global level information. In this study, we compared two groups differing in predominant individualistic (N = 15) vs collectivistic (N = 15) self-orientation. Participants completed a global/local perceptual conflict task whilst undergoing functional Magnetic Resonance Imaging (fMRI) scanning. When participants high in individualistic values attended to the global level (ignoring the local level), greater activity was observed in the frontoparietal and cingulo-opercular networks that underpin attentional control, compared to the match (congruent) baseline. Participants high in collectivistic values activated similar attentional control networks o only when directly compared with global processing. This suggests that global interference was stronger than local interference in the conflict task in the collectivistic group. Both groups showed increased activity in dorsolateral prefrontal regions involved in resolving perceptual conflict during heightened distractor interference. The findings suggest that self-orientation may play an important role in driving attention networks to facilitate interaction with the visual environment. PMID- 26270823 TI - A Case of BK Nephropathy without Detectable Viremia or Viruria. AB - BACKGROUND: BK nephropathy is an evolving challenge among kidney transplant recipients. Diagnosis of BK nephropathy depends on the presence of BK viral inclusions on renal biopsy. Most cases of BK nephropathy are preceded by BK viremia or viruria. CASE REPORT: We report a case of BK nephropathy found on protocol renal transplant biopsy without associated BK viremia or viruria. CONCLUSIONS: BK nephropathy may occur even in the absence of BK viremia or viruria. Protocol biopsy is a useful tool to detect these cases. PMID- 26270822 TI - Next Generation Sequencing Analysis Reveals Segmental Patterns of microRNA Expression in Mouse Epididymal Epithelial Cells. AB - The functional maturation of mammalian spermatozoa is accomplished as the cells descend through the highly specialized microenvironment of the epididymis. This dynamic environment is, in turn, created by the combined secretory and absorptive activity of the surrounding epithelium and displays an extraordinary level of regionalization. Although the regulatory network responsible for spatial coordination of epididymal function remains unclear, recent evidence has highlighted a novel role for the RNA interference pathway. Indeed, as noncanonical regulators of gene expression, small noncoding RNAs have emerged as key elements of the circuitry involved in regulating epididymal function and hence sperm maturation. Herein we have employed next generation sequencing technology to profile the genome-wide miRNA signatures of mouse epididymal cells and characterize segmental patterns of expression. An impressive profile of some 370 miRNAs were detected in the mouse epididymis, with a subset of these specifically identified within the epithelial cells that line the tubule (218). A majority of the latter miRNAs (75%) were detected at equivalent levels along the entire length of the mouse epididymis. We did however identify a small cohort of miRNAs that displayed highly regionalized patterns of expression, including miR 204-5p and miR-196b-5p, which were down- and up-regulated by approximately 39- and 45-fold between the caput/caudal regions, respectively. In addition we identified 79 miRNAs (representing ~ 21% of all miRNAs) as displaying conserved expression within all regions of the mouse, rat and human epididymal tissue. These included 8/14 members of let-7 family of miRNAs that have been widely implicated in the control of androgen signaling and the repression of cell proliferation and oncogenic pathways. Overall these data provide novel insights into the sophistication of the miRNA network that regulates the function of the male reproductive tract. PMID- 26270821 TI - Passive Immunization in JNPL3 Transgenic Mice Using an Array of Phospho-Tau Specific Antibodies. AB - Recent work from our lab and few others have strongly suggested that immunotherapy could be an effective means of preventing the development of tau accumulation in JNPL3 transgenic mice, carrying the human P301L mutation. The aim of this study was to test the efficacy of a variety of specific tau monoclonal antibodies in JNPL3. Starting at 3 months of age, mice were treated for 4 months with weekly intraperitoneal injections of saline or purified tau monoclonal antibodies (10 mg/Kg) different in specificity for pathological tau: CP13 (pSer202), RZ3 (pThr231) and PG5 (pSer409). As expected, not all the antibodies tested showed efficacy at preventing the development of tau pathology at the described dose, with some of them even worsening the pathological scenario. Only by targeting the pSer202 epitope with CP13 was a conspicuous reduction of insoluble or soluble tau in cortex and hindbrain obtained. Here we report about the importance of screening in vivo multiple tau antibodies in order to select the antibodies to direct into future clinical studies. PMID- 26270825 TI - Irrational Exuberance in Testosterone Prescribing: When Will the Bubble Burst? PMID- 26270827 TI - Rural Medicare Beneficiaries Have Fewer Follow-up Visits and Greater Emergency Department Use Postdischarge. AB - BACKGROUND: Hospitals are focused on improving postdischarge services for older adults, such as early follow-up care after hospitalization to reduce readmissions and unnecessary emergency department (ED) use. Rural Medicare beneficiaries face many barriers to receiving quality care, but little is known about their postdischarge care and outcomes. We hypothesize that rural Medicare beneficiaries compared with urban beneficiaries, will have fewer follow-up visits, and a greater likelihood of readmission and ED use. METHODS: We conducted a retrospective analysis of elderly Medicare beneficiaries discharged home using the Medicare Current Beneficiary Survey, Cost and Use files, 2000-2010. Multivariate Cox proportional hazard models were used to assess the risk of rural residency on readmission, ED use, and follow-up care up to 30 days' postdischarge. Covariates include demographic, health, and hospital-level characteristics. RESULTS: Compared with urban beneficiaries, Medicare beneficiaries living in isolated rural settings had a lower rate of follow-up care [hazard ratio (HR)=0.81, P<0.001]. Beneficiaries in large and small rural settings had a greater risk of an ED visit compared with urban beneficiaries (HR=1.44, P<0.001; HR=1.52, P<0.01). Rural beneficiaries did not have a greater risk of readmission, though risk of readmission was higher for beneficiaries discharged from hospitals in large and small rural settings (HR=1.33, P<0.05; HR=1.42, P<0.05). CONCLUSIONS: This study provides evidence of lower quality postdischarge care for Medicare beneficiaries in rural settings. As readmission penalties expand, hospitals serving rural beneficiaries may be disproportionately affected. This suggests a need for policies that increase follow-up care in rural settings. PMID- 26270826 TI - Potentially Preventable Hospitalizations in Medicare Patients With Diabetes: A Comparison of Primary Care Provided by Nurse Practitioners Versus Physicians. AB - BACKGROUND: Few comparisons exist of the quality of primary care provided by nurse practitioners (NPs) versus physicians. METHODS: Patients with a diagnosis of diabetes in 2007-2010 (n=345,819) who received all primary care from NPs or from generalist physicians in a given year were selected from a national sample of Medicare beneficiaries. We compared the rate of potentially preventable hospitalizations among patients who received primary care from NPs versus generalist physicians. Various statistical methods-including multivariable analysis, inverse probability weighting of propensity score, nonpooling propensity score adjustment and matching, and instrumental variable (IV) analysis were used to control for differences in patient characteristics between the 2 groups. RESULTS: Patients who received all of their primary care from NPs or from physicians differed by age, sex, race/ethnicity, socioeconomic status, residential area, and number of provider visits in the previous year. Nonpooling propensity score matching substantially reduced the differences, but neither IV approach satisfactorily reduced the differences. In multivariable analyses, receipt of primary care from an NP was associated with a decreased risk of hospitalization for potentially preventable conditions (OR: 0.90; 95% CI, 0.87 0.93). Similar results were found using conditional logistic regression models with propensity methods. We found smaller reductions in our analyses of "other hospitalizations" (OR: 0.96; 95% CI, 0.95-0.98). Both IV analyses showed associations between NP care and lower potentially preventable hospitalizations, but only 1 result was statistically significant. CONCLUSIONS: Using potentially preventable hospitalizations as a quality indicator, primary care provided by NPs was at least comparable with that provided by generalist physicians. PMID- 26270828 TI - Self-Assembly and Disassembly of Vesicles as Controlled by Anion-pi Interactions. AB - Anion-pi interactions have been widely studied as new noncovalent driving forces in supramolecular chemistry. However, self-assembly induced by anion-pi interactions is still largely unexplored. Herein we report the formation of supramolecular amphiphiles through anion-pi interactions, and the subsequent formation of self-assembled vesicles in water. With the pi receptor 1 as the host and anionic amphiphiles, such as sodium dodecylsulfate (SDS), sodium laurate (SLA), and sodium methyl dodecylphosphonate (SDP), as guests, the sequential formation of host-guest supramolecular amphiphiles and self-assembled vesicles was demonstrated by SEM, TEM, DLS, and XRD techniques. The intrinsic anion-pi interactions between 1 and the anionic amphiphiles were confirmed by crystal diffraction, HRMS analysis, and DFT calculations. Furthermore, the controlled disassembly of the vesicles was promoted by competing anions, such as NO3 (-) , Cl(-) , and Br(-) , or by changing the pH value of the medium. PMID- 26270829 TI - Supramolecular Surface Immobilization of Knottin Derivatives for Dynamic Display of High Affinity Binders. AB - Knottins are known as a robust and versatile class of miniprotein scaffolds for the presentation of high-affinity binding peptides; however, to date their application in biomaterials, biological coatings, and surface applications have not been explored. We have developed a strategy to recombinantly synthesize a beta-trypsin inhibitory knottin with supramolecular guest tags that enable it to adhere to self-assembled monolayers of the supramolecular host cucurbit[8]uril (CB[8]). We have described a strategy to easily express knottins in E. coli by conjugating them to a fluorescent protein after which they are cleaved and purified. Knottin constructs that varied in the number and position of the supramolecular tag at either the N- or C-termini or at both ends have been verified for their trypsin inhibitory function and CB[8]-binding properties in solution and on surfaces. All of the knottin constructs showed strong inhibition of trypsin with inhibition constants between 10 and 30 nM. Using microscale thermophoresis, we determined that the supramolecular guest tags on the knottins bind CB[8] with a Kd of ~6 MUM in solution. At the surface, strong divalent binding has been determined with a Kd of 0.75 MUM in the case of the knottin with two supramolecular guest tags, whereas only weak monovalent binding occurred when only one guest tag was present. We also show successful supramolecular surface immobilization of the knottin using CB[8] and prove that they can be used to immobilize beta-trypsin at the surface. PMID- 26270824 TI - Recent Transmission Clustering of HIV-1 C and CRF17_BF Strains Characterized by NNRTI-Related Mutations among Newly Diagnosed Men in Central Italy. AB - BACKGROUND: Increased evidence of relevant HIV-1 epidemic transmission in European countries is being reported, with an increased circulation of non-B subtypes. Here, we present two recent HIV-1 non-B transmission clusters characterized by NNRTI-related amino-acidic mutations among newly diagnosed HIV-1 infected men, living in Rome (Central-Italy). METHODS: Pol and V3 sequences were available at the time of diagnosis for all individuals. Maximum-Likelihood and Bayesian phylogenetic-trees with bootstrap and Bayesian-probability supports defined transmission-clusters. HIV-1 drug-resistance and V3-tropism were also evaluated. RESULTS: Among 534 new HIV-1 non-B cases, diagnosed from 2011 to 2014, in Central-Italy, 35 carried virus gathering in two distinct clusters, including 27 HIV-1 C and 8 CRF17_BF subtypes, respectively. Both clusters were centralized in Rome, and their origin was estimated to have been after 2007. All individuals within both clusters were males and 37.1% of them had been recently-infected. While C-cluster was entirely composed by Italian men-who-have-sex-with-men, with a median-age of 34 years (IQR:30-39), individuals in CRF17_BF-cluster were older, with a median-age of 51 years (IQR:48-59) and almost all reported sexual-contacts with men and women. All carried R5-tropic viruses, with evidence of atypical or resistance amino-acidic mutations related to NNRTI-drugs (K103Q in C-cluster, and K101E+E138K in CRF17_BF-cluster). CONCLUSIONS: These two epidemiological clusters provided evidence of a strong and recent circulation of C and CRF17_BF strains in central Italy, characterized by NNRTI-related mutations among men engaging in high-risk behaviours. These findings underline the role of molecular epidemiology in identifying groups at increased risk of HIV-1 transmission, and in enhancing additional prevention efforts. PMID- 26270830 TI - Excited-State Structure Modifications Due to Molecular Substituents and Exciton Scattering in Conjugated Molecules. AB - Attachment of chemical substituents (such as polar moieties) constitutes an efficient and convenient way to modify physical and chemical properties of conjugated polymers and oligomers. Associated modifications in the molecular electronic states can be comprehensively described by examining scattering of excitons in the polymer's backbone at the scattering center representing the chemical substituent. Here, we implement effective tight-binding models as a tool to examine the analytical properties of the exciton scattering matrices in semi infinite polymer chains with substitutions. We demonstrate that chemical interactions between the substitution and attached polymer are adequately described by the analytical properties of the scattering matrices. In particular, resonant and bound electronic excitations are expressed via the positions of zeros and poles of the scattering amplitude, analytically continued to complex values of exciton quasi-momenta. We exemplify the formulated concepts by analyzing excited states in conjugated phenylacetylenes substituted by perylene. PMID- 26270831 TI - Electronic Structure of TiO2/CH3NH3PbI3 Perovskite Solar Cell Interfaces. AB - The electronic structure and chemical composition of efficient CH3NH3PbI3 perovskite solar cell materials deposited onto mesoporous TiO2 were studied using photoelectron spectroscopy with hard X-rays. With this technique, it is possible to directly measure the occupied energy levels of the perovskite as well as the TiO2 buried beneath and thereby determine the energy level matching of the interface. The measurements of the valence levels were in good agreement with simulated density of states, and the investigation gives information on the character of the valence levels. We also show that two different deposition techniques give results indicating similar electronic structures. PMID- 26270832 TI - Monitoring TriAcylGlycerols Accumulation by Atomic Force Microscopy Based Infrared Spectroscopy in Streptomyces Species for Biodiesel Applications. AB - An atomic force microscope coupled with a tunable infrared laser source (AFM-IR) was used to measure the size and map the distribution of oil inclusions inside of microorganism without staining or other special sample preparation. The microorganism under study is Streptomyces, a soil bacterium that possesses the capability, under some specific nutritional conditions, to store its carbon source into TriAcylGlycerols, a potential direct source of biodiesel. PMID- 26270833 TI - Generation of Multiple Excitons in Ag2S Quantum Dots: Single High-Energy versus Multiple-Photon Excitation. AB - We explored biexciton generation via carrier multiplication (or multiple-exciton generation) by high-energy photons and by multiple-photon absorption in Ag2S quantum dots (QDs) using femtosecond broad-band transient absorption spectroscopy. Irrespective of the size of the QDs and how the multiple excitons are generated in the Ag2S QDs, two distinct characteristic time constants of 9.6 10.2 and 135-175 ps are obtained for the nonradiative Auger recombination of the multiple excitons, indicating the existence of two binding excitons, namely, tightly bound and weakly bound excitons. More importantly, the lifetimes of multiple excitons in Ag2S QDs were about 1 and 2 orders of magnitude longer than those of comparable size PbS QDs and single-walled carbon nanotubes, respectively. This result is significant because it suggests that by utilizing an appropriate electron acceptor, there is a higher possibility to extract multiple electron-hole pairs in Ag2S QDs, which should improve the performance of QD-based solar cell devices. PMID- 26270834 TI - Water 26-mers Drawn from Bulk Simulations: Benchmark Binding Energies for Unprecedentedly Large Water Clusters and Assessment of the Electrostatically Embedded Three-Body and Pairwise Additive Approximations. AB - It is important to test methods for simulating water, but small water clusters for which benchmarks are available are not very representative of the bulk. Here we present benchmark calculations, in particular CCSD(T) calculations at the complete basis set limit, for water 26-mers drawn from Monte Carlo simulations of bulk water. These clusters are large enough that each water molecule participates in 2.5 hydrogen bonds on average. The electrostatically embedded three-body approximation with CCSD(T) embedded dimers and trimers reproduces the relative binding energies of eight clusters with a mean unsigned error (MUE, kcal per mole of water molecules) of only 0.009 and 0.015 kcal for relative and absolute binding energies, respectively. Using only embedded dimers (electrostatically embedded pairwise approximation) raises these MUEs to 0.038 and 0.070 kcal, and computing the energies with the M11 exchange-correlation functional, which is very economical, yields errors of only 0.029 and 0.042 kcal. PMID- 26270835 TI - Progress in High-Capacity Core-Shell Cathode Materials for Rechargeable Lithium Batteries. AB - High-energy-density rechargeable batteries are needed to fulfill various demands such as self-monitoring analysis and reporting technology (SMART) devices, energy storage systems, and (hybrid) electric vehicles. As a result, high-energy electrode materials enabling a long cycle life and reliable safety need to be developed. To ensure these requirements, new material chemistries can be derived from combinations of at least two compounds in a secondary particle with varying chemical composition and primary particle morphologies having a core-shell structure and spherical cathode-active materials, specifically a nanoparticle core and shell, nanoparticle core and nanorod shell, and nanorod core and shell. To this end, several layer core-shell cathode materials were developed to ensure high capacity, reliability, and safety. PMID- 26270837 TI - Definitions for Hydrophilicity, Hydrophobicity, and Superhydrophobicity: Getting the Basics Right. PMID- 26270836 TI - Role of the Selective Contacts in the Performance of Lead Halide Perovskite Solar Cells. AB - The effect of electron- and hole-selective contacts in the final cell performance of hybrid lead halide perovskite, CH3NH3PbI3, solar cells has been systematically analyzed by impedance spectroscopy. Complete cells with compact TiO2 and spiro OMeTAD as electron- and hole-selective contacts have been compared with incomplete cells without one or both selective contacts to highlight the specific role of each contact. It has been described how selective contacts contribute to enhance the cell FF and how the hole-selective contact is mainly responsible for the high Voc in this kind of device. We have determined that the recombination rate is mainly governed by the selective contacts. This fact has important implication for the future optimization of perovskite solar cells. Finally, we have developed a method to analyze the results obtained, and it has been applied for three different electron-selecting materials: TiO2, ZnO, and CdS. PMID- 26270838 TI - Relaxation of Electron Carriers in the Density of States of Nanocrystalline TiO2. AB - Band gap localized states and surface states play a dominant role in the application of nanocrystalline metal oxides to photovoltaics and solar fuel production. Electrons injected in nanocrystalline TiO2 by voltage or photogeneration are mainly located in band gap states. Therefore, charging a nanoparticulate semiconductor network allows one to recover the density of states (DOS) in the energy axis. However, shallow traps remain in equilibrium with the conduction band electrons, while deep traps do not. We show that the characteristic peak of the apparent DOS mixes an exponential DOS and a monoenergetic surface state. A model that incorporates the trap's kinetics proves to be very efficient to assess the important parameters that determine both contributions via variation of charging rate. Contrary to the common theory, we demonstrate that the peculiar capacitance peak of nanocrystalline TiO2 can be mainly attributed, in some cases, to deep traps in the exponential distribution. PMID- 26270839 TI - Quantitative Analysis of Diffusive Reactions at the Solid-Liquid Interface in Finite Systems. AB - A central element in many processes in physics, chemistry and biology is a reaction between a species immobilized on a surface and a partner that is able to diffuse in solution. However, integrated rate laws for this class of chemical processes have so far only been found in certain special cases. Here, we present a model for the time dependence of an irreversible reaction between particles in a solution of finite volume and a surface. The resulting analytical expression allows quantitative analysis of the transient kinetics of the reaction between soluble particles and a surface. We apply this approach to the analysis of quartz crystal microbalance experiments of protein aggregation under conditions where both reaction and diffusion define the overall kinetics. Furthermore, we use the model to determine absolute mass sensitivity coefficients for soft and rough surfaces, a situation where conventional approaches to determine the mass sensitivity a priori fail. PMID- 26270840 TI - Ring-Polymer Molecular Dynamics Rate Coefficient Calculations for Insertion Reactions: X + H2 -> HX + H (X = N, O). AB - The thermal rate constants of two prototypical insertion-type reactions, namely, N/O + H2 -> NH/OH + H, are investigated with ring polymer molecular dynamics (RPMD) on full-dimensional potential energy surfaces using recently developed RPMDrate code. It is shown that the unique ability of the RPMD approach among the existing theoretical methods to capture the quantum effects, e.g., tunneling and zero-point energy, as well as recrossing dynamics quantum mechanically with ring polymer trajectories leads to excellent agreement with rigorous quantum dynamics calculations. The present result is encouraging for future applications of the RPMD method and the RPMDrate code to complex-forming chemical reactions involving polyatomic reactants. PMID- 26270841 TI - Quasiclassical Trajectory Calculations of the Rate Constant of the OH + HBr -> Br + H2O Reaction Using a Full-Dimensional Ab Initio Potential Energy Surface Over the Temperature Range 5 to 500 K. AB - We report a permutationally invariant, ab initio potential energy surface (PES) for the OH + HBr -> Br + H2O reaction. The PES is a fit to roughly 26 000 spin free UCCSD(T)/cc-pVDZ-F12a energies and has no classical barrier to reaction. It is used in quasiclassical trajectory calculations with a focus on the thermal rate constant, k(T), over the temperature range 5 to 500 K. Comparisons with available experimental data over the temperature range 23 to 416 K are made using three approaches to treat the OH rotational and associated electronic partition function. All display an inverse temperature dependence of k(T) below roughly 160 K and a nearly constant temperature dependence above 160 K, in agreement with experiment. The calculated rate constant with no treatment of spin-orbit coupling is overall in the best agreement with experiment, being (probably fortuitously) within 20% of it. PMID- 26270842 TI - A Simple Solution to the Trivial Crossing Problem in Surface Hopping. AB - Surface hopping studies on supramolecular and nanoscale systems suffer severely from the trivial crossing problem, arising due to high density of adiabatic potential energy surfaces. We present a straightforward solution to the problem by introducing a self-consistency test to the well-known fewest switches surface hopping (FSSH) procedure. If the test is failed, the hopping probabilities are corrected with a simple procedure. The novel self-consistent fewest switches surface hopping (SC-FSSH) approach is applied to the Holstein Hamiltonian to study the time-dependence of the electron population. Already in the five-state system, SC-FSSH allows us to reduce the simulation time 10(4)-fold to achieve the FSSH accuracy. The reliable performance and simple formulation of SC-FSSH greatly expands the applicability range of the surface hopping method. PMID- 26270843 TI - One-Dimensional Silicon Nanostructures for Li Ion Batteries. AB - One dimensional (1D) silicon nanostructures have attracted significant interest as an anode material for lithium ion batteries (LIBs) as its 1D geometry accommodates the large volume change of the Si during cycling and enables facile electron transport during all stages of operation. Furthermore, the high aspect ratio of 1D Si nanostructures enables us to investigate atomic-scale mechanisms of the lithiation process and corresponding volume change behavior. Various 1D nanostructures with different morphologies and compositions have been explored to achieve a robust cycle performance, reversible morphological changes, and high rate capabilities. In this Perspective, we summarize the recent significant advances of 1D Si nanostructures and discuss electrode design strategies based on the recent geometry and composition engineering. PMID- 26270844 TI - Efficient Superionic Conductor Catalyst for Solid in Solution-Solid-Solid Growth of Heteronanowires. AB - How efficient could a superionic conductor catalyst be? Beyond the traditionally used molecular precursors when the solution dispersed solid nanomaterials of variable size, shape and phase are introduced under certain reaction condition; the catalyst is found to digest all these structures in minutes irrespective of their phase and morphology, resulting unique heteronanowires. This has been inspected here by employing different ZnSe nanostructures as precursor for Ag2Se nanocrystal catalyst in its superionic conductor phase to obtain the Ag2Se-ZnSe heteronanowires. This dissolution and formation process of these nanostructures is correlated with the change in the reaction temperature profile, the phase of the catalyst, the shape/phase and surface ligands of the source nanostructures, and the possible mechanism of the unique heteronanowires growth has been investigated. PMID- 26270845 TI - Observation of Universal Solidification in the Elongated Water Nanomeniscus. AB - The ubiquitous capillary water bridge in nature plays an important role in interfacial phenomena under ambient conditions such as adhesion and friction. We present experimental measurements of the mechanical properties of the nanometric water column by using noncontact atomic force microscopy. We observe the universal behaviors that the relaxation time (RT) associated with the meniscus increases with its elongation and ruptures at the same value of RT, independent of the meniscus volume. In particular, the enhancement of RT between formation and rupture of the meniscus is indicative of the increased solid-like response, similar to that observed in nanoconfined water layers. Our results that the longer water column is more solid-like and less stable suggest (i) water at the vapor/liquid interface is more solid-like than that inside the meniscus and (ii) the associated smaller mobility of the interfacial water molecules is responsible for the structural stability of the water meniscus. PMID- 26270846 TI - Spacing-Dependent Antimicrobial Efficacy of Immobilized Silver Nanoparticles. AB - Silver nanoparticles (Ag NPs) with a similar mean particle diameter (~5.0 nm) but distinguished dispersion densities were in situ fabricated and immobilized on plasma-sprayed titanium oxide coatings by a silver plasma immersion ion implantation process (Ag PIII). Experiments and theoretical predictions demonstrated that the efficacy of these Ag NPs against bacteria relies on their electron storage capability, which is the interparticle distance associated in the dark, and it is inversely dose-dependent. A particle population with a relatively large spacing distance is superior in concentrating the electrons extruded by bacterial cells, activating oxidative reactions, and disrupting the bacterial cells. The finding opens up a new window leading to active design and control of the interactions between materials and biological systems. PMID- 26270847 TI - Nanomaterials Developments for Higher-Performance Lithium Ion Batteries. PMID- 26270848 TI - Penetration Barrier of Water through Graphynes' Pores: First-Principles Predictions and Force Field Optimization. AB - Graphynes are novel two-dimensional carbon-based materials that have been proposed as molecular filters, especially for water purification technologies. We carry out first-principles electronic structure calculations at the MP2C level of theory to assess the interaction between water and graphyne, graphdiyne, and graphtriyne pores. The computed penetration barriers suggest that water transport is unfeasible through graphyne while being unimpeded for graphtriyne. For graphdiyne, with a pore size almost matching that of water, a low barrier is found that in turn disappears if an active hydrogen bond with an additional water molecule on the opposite side of the opening is considered. Thus, in contrast with previous determinations, our results do not exclude graphdiyne as a promising membrane for water filtration. In fact, present calculations lead to water permeation probabilities that are 2 orders of magnitude larger than estimations based on common force fields. A new pair potential for the water carbon noncovalent component of the interaction is proposed for molecular dynamics simulations involving graphdiyne and water. PMID- 26270849 TI - Substrate Inhibition in Human Indoleamine 2,3-Dioxygenase. AB - Human indoleamine 2,3-dioxygenase (hIDO) catalyzes the oxidative cleavage of the L-tryptophan (l-Trp) pyrrole ring. Catalysis is inhibited at high substrate concentrations; mechanistic details of this observation are, however, still under debate. Using time-resolved optical spectroscopy, we have analyzed the dynamics of ternary complex formation between hIDO, l-Trp, and a diatomic ligand. The physiological ligand dioxygen (O2) was replaced by carbon monoxide to exclude enzymatic turnover. Quantitative analysis of the kinetics reveals that the ternary complex forms whenever O2 binds first, whereas an l-Trp substrate molecule arriving prior to O2 in the active site causes self-inhibition. Bound l Trp prevents the ligand from approaching the heme iron and, therefore, impedes formation of the catalytically active ternary complex. PMID- 26270850 TI - Evaluation of pH at Charged Lipid/Water Interfaces by Heterodyne-Detected Electronic Sum Frequency Generation. AB - Although the interface pH at a biological membrane is important for biological processes at the membrane, there has been no systematic study to evaluate it. We apply novel interface-selective nonlinear spectroscopy to the evaluation of the pH at model biological membranes (lipid/water interfaces). It is clearly shown that the pH at the charged lipid/water interfaces is substantially deviated from the bulk pH. The pH at the lipid/water interface is higher than that in the bulk when the head group of the lipid is positively charged, whereas the pH at the lipid/water interface is lower when the lipid has a negatively charged head group. PMID- 26270851 TI - ASSOCIATION OF SUBJECTIVE RATINGS TO OBJECTIVELY ASSESSED PHYSICAL ACTIVITY IN PUBERTAL BOYS WITH DIFFERING BMI. AB - The associations between subjective ratings and objectively measured moderate-to vigorous physical activity (MVPA) were examined in normal, and overweight and obese, pubertal boys and compared with their parents' reports. In total, 224 boys (M age=12.2 yr.) completed the self-report questionnaire and wore an accelerometer for 7 consecutive days. Questionnaire-based indexes of physical activity (PA) were weakly associated with the accelerometer PA data. Correlations between subjective and objective assessments were significantly higher in overweight and obese groups. Parent reports predicted sedentary time better than boys' self-reports but no difference was found for MVPA. Future studies must consider that the source of rating, season, and weight status may be possible sources of confounding when using subjective assessments of PA. PMID- 26270852 TI - FUNDAMENTAL MOVEMENT SKILLS OF PRESCHOOL CHILDREN IN NORTHWEST ENGLAND. AB - This cross-sectional study examined fundamental movement skill competency among deprived preschool children in Northwest England and explored sex differences. A total of 168 preschool children (ages 3-5 yr.) were included in the study. Twelve skills were assessed using the Children's Activity and Movement in Preschool Motor Skills Protocol and video analysis. Sex differences were explored at the subtest, skill, and component levels. Overall competence was found to be low among both sexes, although it was higher for locomotor skills than for object control skills. Similar patterns were observed at the component level. Boys had significantly better object-control skills than girls, with greater competence observed for the kick and overarm throw, while girls were more competent at the run, hop, and gallop. The findings of low competency suggest that developmentally appropriate interventions should be implemented in preschool settings to promote movement skills, with targeted activities for boys and girls. PMID- 26270853 TI - THE LAUNCH WINDOW HYPOTHESIS AND THE SPEED-ACCURACY TRADE-OFF IN BASEBALL THROWING. AB - The speed-accuracy trade-off in throwing has been well described, but its cause is poorly understood. The popular impulse-variability hypothesis lacks relevance to throwing, while the launch window hypothesis has explanatory potential but has not been empirically tested. The current study therefore aimed to quantify the speed-accuracy trade-off and launch window during a throwing task at two different speeds. Nine elite junior baseball players (M age=19.6 yr.; M height=1.80 m; M weight=75.5 kg) threw 10 fastballs at 80 and 100% of maximal throwing speed (MTS) toward a 7 cm target from a distance of 20 m. A 3D motion analysis system measured ball speed and trajectory. A speed-accuracy trade-off occurred, mediated by increased vertical error. This can be attributed to the launch window, which was significantly smaller, particularly its vertical component, during 100% MTS. Maximal throwing speed correlated negatively with launch window size. The launch window hypothesis explained the observed speed accuracy trade-off, providing a framework within which aspects of technique can be identified and altered to improve performance. PMID- 26270854 TI - Single Superficial versus Dual Systems Venous Anastomoses in Radial Forearm Free Flap: A Meta-Analysis. AB - BACKGROUND: The radial forearm free flap (RFFF) has been widely used with increasing frequency in head and neck reconstruction following extirpative surgery. The controversy of the venous anastomoses patterns still exists. Thus, we conducted a meta-analysis to assess the relationship between the venous anastomoses patterns and venous compromise. METHODS: MEDLINE, PubMed, Web of Science, and Wanfang databases were searched for studies reporting the different venous anastomoses patterns of the RFFF. A meta-analysis was conducted using the random effects models. Publication bias and sensitivity analysis were also assessed. RESULTS: 6 studies with 992 cases were included in this meta-analysis. The dual anastomosis group tended to have a lower incidence of venous compromise (RR = 1.39). However, the difference was not statistically significant (95%CI: 0.59, 3.24). CONCLUSIONS: This meta-analysis indicated that performing dual venous anatomoses consisting of superficial and deep systems conferred a tendency of the reduction with regard to venous compromise. PMID- 26270855 TI - Nutritional risk assessment in critically ill cancer patients: systematic review. AB - OBJECTIVE: To systematically review the main methods for nutritional risk assessment used in critically ill cancer patients and present the methods that better assess risks and predict relevant clinical outcomes in this group of patients, as well as to discuss the pros and cons of these methods according to the current literature. METHODS: The study consisted of a systematic review based on analysis of manuscripts retrieved from the PubMed, LILACS and SciELO databases by searching for the key words "nutritional risk assessment", "critically ill" and "cancer". RESULTS: Only 6 (17.7%) of 34 initially retrieved papers met the inclusion criteria and were selected for the review. The main outcomes of these studies were that resting energy expenditure was associated with undernourishment and overfeeding. The high Patient-Generated Subjective Global Assessment score was significantly associated with low food intake, weight loss and malnutrition. In terms of biochemical markers, higher levels of creatinine, albumin and urea were significantly associated with lower mortality. The worst survival was found for patients with worse Eastern Cooperative Oncologic Group - performance status, high Glasgow Prognostic Score, low albumin, high Patient-Generated Subjective Global Assessment score and high alkaline phosphatase levels. Geriatric Nutritional Risk Index values < 87 were significantly associated with mortality. A high Prognostic Inflammatory and Nutritional Index score was associated with abnormal nutritional status in critically ill cancer patients. Among the reviewed studies that examined weight and body mass index alone, no significant clinical outcome was found. CONCLUSION: None of the methods reviewed helped to define risk among these patients. Therefore, assessment by a combination of weight loss and serum measurements, preferably in combination with other methods using scores such as Eastern Cooperative Oncologic Group - performance status, Glasgow Prognostic Score and Patient-Generated Subjective Global Assessment, is suggested given that their use is simple, feasible and useful in such cases. PMID- 26270856 TI - Maternal near miss in the intensive care unit: clinical and epidemiological aspects. AB - OBJECTIVE: To analyze the epidemiological clinical profile of women with maternal near miss according to the new World Health Organization criteria. METHODS: A descriptive cross-sectional study was conducted, in which the records of patients admitted to the obstetric intensive care unit of a tertiary hospital in Recife (Brazil) over a period of four years were analyzed. Women who presented at least one near miss criterion were included. The variables studied were age, race/color, civil status, education, place of origin, number of pregnancies and prenatal consultations, complications and procedures performed, mode of delivery, gestational age at delivery, and maternal near miss criteria. The descriptive analysis was performed using the program Epi-Info 3.5.1. RESULTS: Two hundred fifty-five cases of maternal near miss were identified, with an overall ratio of maternal near miss of 12.8/1,000 live births. Among these cases, 43.2% of the women had incomplete primary education, 44.7% were primiparous, and 20.5% had undergone a previous cesarean section. Regarding specific diagnoses, there was a predominance of hypertensive disorders (62.7%), many of which were complicated by HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome (41.2%). The laboratory near miss criteria were the most often observed (59.6%), due mainly to the high frequency of acute thrombocytopenia (32.5%). CONCLUSIONS: A high frequency of women who had a low level of education and who were primiparous was observed. According to the new criteria proposed by the World Health Organization, hypertensive pregnancy disorders are still the most common among maternal near miss cases. The high frequency of HELLP syndrome was also striking, which contributed to acute thrombocytopenia being the most frequent near miss criterion. PMID- 26270858 TI - Role of Local Radiation Therapy in Cancer Immunotherapy. AB - The recent success of cancer immunotherapy has demonstrated the power of the immune system to clear tumors, generating renewed enthusiasm for identifying ways to induce antitumor immune responses in patients. Natural antitumor immune responses are detectable in a fraction of patients across multiple malignant neoplasms and can be reactivated by targeting rate-limiting immunosuppressive mechanisms. In most patients, however, interventions to induce a de novo antitumor immune response are necessary. We review growing evidence that radiation therapy targeted to the tumor can convert it into an in situ tumor vaccine by inducing release of antigens during cancer cell death in association with proinflammatory signals that trigger the innate immune system to activate tumor-specific T cells. In addition, radiation's effects on the tumor microenvironment enhance infiltration of activated T cells and can overcome some of the barriers to tumor rejection. Thus, the complementary effects of radiation on priming and effector phases of antitumor immunity make it an appealing strategy to generate immunity against a patient's own individual tumor, that through immunological memory, can result in long-lasting systemic responses. Several anecdotal cases have demonstrated the efficacy of combining radiation with available immunotherapies, and results of prospective trials are forthcoming. PMID- 26270857 TI - Mechanism of the Intramolecular Hexadehydro-Diels-Alder Reaction. AB - Theoretical analysis of the mechanism of the intramolecular hexadehydro-Diels Alder (HDDA) reaction, validated against prior and newly measured kinetic data for a number of different tethered yne-diynes, indicates that the reaction proceeds in a highly asynchronous fashion. The rate-determining step is bond formation at the alkyne termini nearest the tether, which involves a transition state structure exhibiting substantial diradical character. Whether the reaction then continues to close the remaining bond in a concerted fashion or in a stepwise fashion (i.e., with an intervening intermediate) depends on the substituents at the remaining terminal alkyne positions. Computational modeling of the HDDA reaction is complicated by the significant diradical character that arises along the reaction coordinate, which leads to instabilities in both restricted singlet Kohn-Sham density functional theory (DFT) and coupled cluster theory based on a Hartree-Fock reference wave function. A consistent picture emerges, however, from comparison of broken-symmetry DFT calculations and second order perturbation theory based on complete-active-space self-consistent-field (CASPT2) calculations. PMID- 26270860 TI - Exacerbation of Psoriasis During Nivolumab Therapy for Metastatic Melanoma. PMID- 26270859 TI - A Novel 6'-N-Aminoglycoside Acetyltransferase, AAC(6')-Ial, from a Clinical Isolate of Serratia marcescens. AB - Serratia marcescens IOMTU115 has a novel 6'-N-aminoglycoside acetyltransferase encoding gene, aac(6')-Ial. The encoded protein AAC(6')-Ial has 146 amino acids, with 91.8% identity to the amino acid sequence of AAC(6')-Ic in S. marcescens SM16 and 97.3% identity to the amino acid sequence of AAC(6')-Iap in S. marcescens WW4. The minimum inhibitory concentrations of aminoglycosides for Escherichia coli expressing AAC(6')-Ial were similar to those for E. coli expressing AAC(6')-Ic or AAC(6')-Iap. Thin-layer chromatography showed that AAC(6')-Ial, AAC(6')-Ic, or AAC(6')-Iap acetylated all the aminoglycosides tested, except for apramycin, gentamicin, and lividomycin. Kinetics assays revealed that AAC(6')-Ial is a functional acetyltransferase against aminoglycosides. The aac(6')-Ial gene was located on chromosomal DNA. PMID- 26270862 TI - What are the predictive factors in the risk and severity of chemotherapy-induced gastrointestinal toxicity? PMID- 26270863 TI - Analysis of Accelerants in Fire Debris - Data Interpretation. AB - Analysis of accelerants in fire debris involves the isolation of residual volatiles from the matrix and the analysis of these volatiles, usually by gas chromatography (GC). The resulting chromatograms are interpreted by comparing to a library of accelerant chromatograms obtained under similar conditions. This review first mentions ASTM's system in classifying fire accelerants into light petroleum distillates, gasoline, medium petroleum distillates, kerosene, heavy petroleum distillates, and unclassified compounds. Chromatograms with well resolved n-alkane homolog patterns are most recognizable. Chromatograms that are inadequately resolved can be improved by columns having higher efficiency or selectivity, while those with too much interference can be improved by physical removal or reduction of these interfering compounds or selective detection. Using a mass spectrometer (MS) as the detector in GC/MS applications allows the display of common ions shared by compounds with similar structural features, thus greatly facilitating pattern recognition practices. Computer algorithms are now available for automated recognition of patterns possessed by various categories of accelerants. The state-of-the-art in forensic laboratories' analysis of accelerants in fire debris is presented as an appendix to this review. Data generated in annual proficiency tests over an 8-year period (1987-1995) revealed increased use of GC/MS instrumentation and some persisting problems, which include false positives and difficulties associated with component discrimination in the sample preparation process and recognition of partially evaporated distillates. PMID- 26270864 TI - Testing for Drugs of Abuse in Hair - Experimental Observations and Indications for Future Research. AB - The testing of hair for drugs of abuse is gaining popularity primarily due to the possibility that hair concentrations of drugs will reflect drug exposure for a longer period of time than either plasma or urine. Data produced by experimental research, rather than those resulting from anecdotal observations, uncontrolled research, or irrelevant experimental models, will be more likely to prove whether this is true and to determine whether drug concentrations in hair can be accurately interpreted in relation to drug dosage. Experimental observations have established that: (a) parent drug concentrations in hair are generally greater than their metabolites; (b) chemical structure of the drug is important in determining its incorporation into hair; (c) pigmentation of hair plays an important role in determining drug incorporation. Data resulting from models (including animal models, in vitro models, transplantation of human hair onto athymic mice, and human subjects) designed for studying hypotheses concerning the mechanism of drug incorporation into hair are also reviewed. PMID- 26270865 TI - Visual Color Comparisons in Forensic Science. AB - Color is used extensively in forensic science for the characterization and comparison of physical evidence, and should thus be well understood. Fundamental elements of color perception and color comparison systems are first reviewed. The second portion of this article discusses instances in which defects in color perception may occur, and the recognition of opportunities by means of which color perception and color discrimination may be expressed and enhanced. Application and limitations of color comparisons in forensic science, including soil, paint, and fibers comparisons and color tests, are reviewed. PMID- 26270861 TI - Recognition of Damaged DNA for Nucleotide Excision Repair: A Correlated Motion Mechanism with a Mismatched cis-syn Thymine Dimer Lesion. AB - Mammalian global genomic nucleotide excision repair requires lesion recognition by XPC, whose detailed binding mechanism remains to be elucidated. Here we have delineated the dynamic molecular pathway and energetics of lesion-specific and productive binding by the Rad4/yeast XPC lesion recognition factor, as it forms the open complex [Min, J. H., and Pavletich, N. P. (2007) Nature 449, 570-575; Chen, X., et al. (2015) Nat. Commun. 6, 5849] that is required for excision. We investigated extensively a cis-syn cyclobutane pyrimidine dimer in mismatched duplex DNA, using high-level computational approaches. Our results delineate a preferred correlated motion mechanism, which provides for the first time an atomistic description of the sequence of events as Rad4 productively binds to the damaged DNA. PMID- 26270867 TI - The Potential Hazards of Hospital Consolidation: Implications for Quality, Access, and Price. PMID- 26270866 TI - Assessment of the Breakaway Torque at the Posterior Pelvic Ring in Human Cadavers. AB - PURPOSE: To enhance the diminished screw purchase in cancellous, osteoporotic bone following the fixation of posterior pelvic ring injuries by iliosacral screws an increased bone-implant contact area using modificated screws, techniques or bone cement may become necessary. The aim of the study was to identify sites within the pathway of iliosacral screws requiring modifications of the local bone or the design of instrumentations placed at this site. MATERIALS AND METHODS: The breakaway torque was measured mechanically at the iliosacral joint ("ISJ"), the sacral lateral mass ("SLM") and the center of the S1 ("CS1"), at a superior and an inferior site under fluoroscopic control on five human cadaveric specimens (3 female; mean age 87 years, range: 76-99) using the DensiProbeTMSpine device. RESULTS: The measured median (range) breakaway torque was 0.63 Nm (0.31-2.52) at the "iliosacral joint", 0.14 Nm (0.05-1.22) at the "sacral lateral mass", 0.57 Nm (0.05-1.42) at the "S1 center." The "sacral lateral mass" breakaway torque was lower than compared to that at the "iliosacral joint" (p < .001) or "S1 center" (p < .001). The median (range) breakaway torque measured at all superior measurement points was 0.52 Nm (0.10-2.52), and 0.48 Nm (0.05-1.18) at all inferior sites. The observed difference was statistically significant (p < .05). CONCLUSIONS: The lateral mass of the sacrum provides the lowest bone quality for implant anchorage. Iliosacral screws should be placed as superior as safely possible, should bridge the iliosacral joint and may allow for cement application at the lateral mass of the sacrum through perforations. PMID- 26270868 TI - Topology optimization for the design of folding liquid crystal elastomer actuators. AB - Aligned liquid crystal elastomers (LCEs) are capable of undergoing large reversible shape change in response to thermal stimuli and may act as actuators for many potential applications such as self-assembly and deployment of micro devices. Recent advances in LCE patterning tools have demonstrated sub-millimetre control of director orientation, enabling the preparation of materials with arbitrarily complex director fields. However, without design tools to connect the 2D director pattern with the activated 3D shape, LCE design relies on intuition and trial and error. Here we present a design methodology to generate reliable folding in monolithic LCEs designed with topology optimization. The distributions of order/disorder and director orientations are optimized so that the remotely actuated deformation closely matches a target deformation for origami folding. The optimal design exhibits a strategy to counteract the mechanical frustration that may lead to an undesirable deformation, such as anti-clastic bending. Multi hinge networks were developed using insights from the optimal hinge designs and were demonstrated through the fabrication and reversible actuation of a self folding box. Topology optimization provides an important step towards leveraging the opportunities afforded by LCE patterning into functional designs. PMID- 26270870 TI - Medicine's Valuing of "Normal" Cognitive Ability. PMID- 26270871 TI - Assessing Information from Pharmaceutical Company Representatives. PMID- 26270872 TI - Donations of Expensive Equipment for Resident Training. PMID- 26270869 TI - The Benefits of Goal Adjustment Capacities for Well-Being Among Women With Breast Cancer: Potential Mechanisms of Action. AB - Breast cancer can seriously disrupt a person's important life goals. As such, the ability to adjust one's goals may be critical for well-being. The present study investigated the relationships between disengagement/reengagement capacity and well-being among women with breast cancer, as well as several potential mechanisms (intrusive thoughts, life purpose, and physical activity) that could explain these relationships. The sample consisted of 230 women with early-stage (n = 172) or late-stage (n = 58) breast cancer, who were followed prospectively for 8 months. Well-being measures consisted of global mental health, perceived physical health, positive/negative affect, and sleep efficiency. Disengagement capacity did not predict any outcome variable. In contrast, reengagement capacity prospectively predicted changes in global mental health, positive affect, negative affect, sleep efficiency, life purpose, and physical activity. Life purpose mediated the prospective relationship between reengagement capacity and multiple aspects of well-being. The relationships between purpose and positive/negative affect were reciprocal over time. Results also suggested that physical activity is not a mediator, but is in fact a result of the effect of reengagement capacity on well-being. The results demonstrate that reengagement capacity is important for well-being among women with breast cancer. PMID- 26270873 TI - Teaching Medical Business Ethics: An Introduction to the Bander Center's Casebook. PMID- 26270874 TI - Pricing Cancer Drugs: When Does Pricing Become Profiteering? PMID- 26270875 TI - The Affordable Care Act and Insurer Business Practices. PMID- 26270876 TI - A Legal Test for the Pharmaceutical Company Practice of "Product Hopping". PMID- 26270877 TI - IRS Rules Will Not Stop Unfair Hospital Billing and Collection Practices. PMID- 26270878 TI - The All-Payer Rate Setting Model for Pricing Medical Services and Drugs. PMID- 26270879 TI - Policymaking for Orphan Drugs and Its Challenges. PMID- 26270880 TI - Money and Medicine: Indivisible and Irreconcilable. PMID- 26270881 TI - Mixing Dinner and Drugs-Is It Ethically Contraindicated? PMID- 26270882 TI - PSYCHE CPMG-HSQMBC: An NMR Spectroscopic Method for Precise and Simple Measurement of Long-Range Heteronuclear Coupling Constants. AB - Among the NMR spectroscopic parameters, long-range heteronuclear coupling constants convey invaluable information on torsion angles relevant to glycosidic linkages of carbohydrates. A broadband homonuclear decoupled PSYCHE CPMG-HSQMBC method for the precise and direct measurement of multiple-bond heteronuclear couplings is presented. The PSYCHE scheme built into the pulse sequence efficiently eliminates unwanted proton-proton splittings from the heteronuclear multiplets so that the desired heteronuclear couplings can be determined simply by measuring frequency differences between peak maxima of pure antiphase doublets. Moreover, PSYCHE CPMG-HSQMBC can provide significant improvement in sensitivity as compared to an earlier Zangger-Sterk-based method. Applications of the proposed pulse sequence are demonstrated for the extraction of (n)J((1)H,(77)Se) and (n)J((1)H,(13)C) values, respectively, in carbohydrates; further extensions can be envisioned in any J-based structural and conformational studies. PMID- 26270883 TI - Lactogenic Activity of an Enzymatic Hydrolysate from Octopus vulgaris and Carica papaya in SD Rats. AB - The traditional Chinese medicine theory believes that octopus papaya soup can stimulate milk production in lactating women. The objective of this study was to determine whether dietary supplementation with an enzymatic hydrolysate of Octopus vulgaris and Carica papaya (EHOC) could increase milk production and nutritional indexes in Sprague Dawley (SD) rats. Female SD rats (n = 24) were fed a control diet (n = 8), EHOC-supplemented diet, or a positive control diet (Shengruzhi) from day 10 of pregnancy to day 10 of lactation. Maternal serum, mammary gland (day 10 of lactation), milk, and pup weight (daily) were collected for analysis. Results showed that the EHOC diet obviously elevated daily milk yield and pup weight compared to the control group (P < .05). The EHOC diet was found to increase the concentration of prolactin (PRL), progesterone (P), estradiol (E2), and growth hormone (GH) significantly in the circulation and mammary gland. Mammary glands of EHOC-treated dams showed clear lobuloalveolar development and proliferation of myoepithelial cells, but no striking variations were observed among the groups. Furthermore, the nutrition content and immune globulin concentration in the milk of EHOC-supplemented dams were higher than those of the control group, especially the cholesterol, glucose, and IgG were higher by 44.98% (P < .001), 42.76% (P < .01), and 42.23% (P < .01), respectively. In conclusion, this article demonstrates that EHOC administration has beneficial effects on milk production in the dams and on performance of the dam and pup. These results indicate that EHOC could be explored as a potentially lactogenic nutriment for lactating women. PMID- 26270884 TI - Time-resolved optically stimulated luminescence of Al2O3:C for ion beam therapy dosimetry. AB - The objective of this study was to characterize the time-resolved (TR) optically stimulated luminescence (OSL) from Al2O3:C detectors and investigate methodologies to improve the accuracy of these detectors in ion beam therapy dosimetry, addressing the reduction in relative response to high linear energy transfer (LET) particles common to solid-state detectors. Al2O3:C OSL detectors (OSLDs) were exposed to proton, (4)He, (12)C and (16)O beams in 22 particle/energy combinations and read using a custom-built TR-OSL reader. The OSL response rOSL, relative to (60)Co gamma dose to water, and the ratio between the UV and blue OSL emission bands of Al2O3:C (UV/blue ratio) were determined as a function of the LET. Monte-Carlo simulations with the multi-purpose interaction and transport code FLUKA were used to estimate the absorbed doses and particle energy spectra in the different irradiation conditions. The OSL responses rOSL varied from 0.980 (0.73 keV MUm(-1)) to 0.288 (120.8 keV MUm(-1)). The OSL UV/blue ratio varied by a factor of two in the investigated LET range, but the variation for (12)C beams was only 11%. OSLDs were also irradiated at different depths of carbon ion spread-out Bragg peaks (SOBPs), where it was shown that doses could be obtained with an accuracy of +/- 2.0% at the entrance channel and within the SOBP using correction factors calculated based on the OSL responses obtained in this study. The UV/blue ratio did not allow accurate estimation of the dose-averaged LET for (12)C SOBPs, although the values obtained can be explained with the data obtained in this study and the additional information provided by the Monte-Carlo simulations. The results demonstrate that accurate OSLD dosimetry can be performed in ion beam therapy using appropriate corrections for the OSL response. PMID- 26270886 TI - Hemodialysis for the treatment of dabigatran-associated bleeding: a case report and systematic review. AB - BACKGROUND: Dabigatran, a direct thrombin inhibitor, is effective for the treatment of venous thromboembolism and the prevention of stroke and systemic embolism resulting from atrial fibrillation. The most effective way of reversing the anticoagulant effect of dabigatran in patients who have bleeding complications is unknown. OBJECTIVES: To document the clinical outcomes of patients undergoing renal replacement therapy (RRT) for dabigatran-associated bleeding. METHODS: We searched MEDLINE and EMBASE up to May 2015. Articles were selected if the patients presented with dabigatran-associated bleeding, underwent RRT for dabigatran removal, and reported an effect on bleeding. RESULTS: The search yielded 22 studies representing 35 unique patient cases. The median patient age was 74.1 years (range, 56-94 years). Thirteen patients (37.1%) were female, and 32 (91.4%) patients received dabigatran for atrial fibrillation. Twenty-three patients (65.7%) underwent intermittent hemodialysis, 10 patients (28.6%) underwent continuous RRT (CRRT), and two patients underwent both intermittent hemodialysis and CRRT. Following RRT, there were significant reductions in dabigatran concentrations (P = 0.001). Rebound of the dabigatran concentration was reported in 12 (57.1%) patients following cessation of RRT. Hemostasis was reportedly achieved in 24 patients (70.6%), and 10 patients (29.4%) died because of bleeding. CONCLUSIONS: In patients with dabigatran associated bleeding, RRT appears to be effective in reducing dabigatran concentrations, and in case reports this has been associated with a reduction in the duration and/or severity of bleeding. However, a rebound in concentrations may be seen following withdrawal of RRT, suggesting that a prolonged course of RRT may be more effective. PMID- 26270885 TI - Development of novel AAV serotype 6 based vectors with selective tropism for human cancer cells. AB - Viral vectors-based gene therapy is an attractive alternative to common anti cancer treatments. In the present studies, AAV serotype 6 vectors were identified to be particularly effective in the transduction of human prostate (PC3), breast (T47D) and liver (Huh7) cancer cells. Next, we developed chimeric AAV vectors with Arg-Gly-Asp (RGD) peptide incorporated into the viral capsid to enable specific targeting of integrin-overexpressing malignant cells. These AAV6-RGD vectors improved transduction efficiency approximately 3-fold compared with wild type AAV6 vectors by enhancing the viral entry into the cells. We also observed that transduction efficiency significantly improved, up to approximately 5-fold, by the mutagenesis of surface-exposed tyrosine and threonine residues involved in the intracellular trafficking of AAV vectors. Therefore, in our study, the AAV6 Y705-731F+T492V vector was identified as the most efficient. The combination of RGD peptide, tyrosine and threonine mutations on the same AAV6 capsid further increased the transduction efficiency, approximately 8-fold in vitro. In addition, we mutated lysine (K531E) to impair the affinity of AAV6 vectors to heparan sulfate proteoglycan. Finally, we showed a significant increase in both specificity and efficiency of AAV6-RGD-Y705-731F+T492V+K531E vectors in a xenograft animal model in vivo. In summary, the approach described here can lead to the development of AAV vectors with selective tropism to human cancer cells. PMID- 26270888 TI - Endocrine stress responses and risk of type 2 diabetes mellitus. AB - This study was carried to ascertain whether stress responses are associated with abnormalities in glucose tolerance, insulin sensitivity and pancreatic beta cell function and risk of type 2 Diabetes Mellitus. Salivary cortisol, a marker of hypothalamic-pituitary-adrenal (HPA) axis and salivary alpha-amylase, a marker of sympathetic nervous system (SNS) were compared in 125 subjects of newly detected diabetes mellitus (NDDM) and normal glucose tolerance (NGT) subjects who were diagnosed on the basis of oral glucose tolerance test (OGTT). Assessment of stress in them was done through stress scales - presumptive stressful life events scale (PSLES), perceived stress scale (PSS) and sense of coherence (SOC) and correlated with these and other stress response markers. Significantly higher 10 pm salivary cortisol and post dexamethasone salivary cortisol were found in NDDM subjects as compared to NGT. 10 pm salivary cortisol correlated significantly with fasting plasma glucose (FPG), 2 h plasma glucose (2h PG) and glycated hemoglobin (HbA1c) while post dex salivary cortisol correlated with 2h PG, HbA1c and salivary alpha-amylase with 2h PG. Stepwise logistic regression analysis showed that body mass index (OR: 1.840), SOC (OR: 0.688) and 10 pm salivary cortisol (OR: 1.427) were the strongest predictors of NDDM. The results of the present study indicate that NDDM subjects display significantly higher chronic stress and stress responses when compared to subjects with NGT. Chronic stress and endocrine stress responses are significantly associated with glucose intolerance, insulin resistance and diabetes mellitus. PMID- 26270887 TI - Effects of a process-based cognitive training intervention for patients with stress-related exhaustion. AB - Stress-related exhaustion has been linked to a pattern of selective cognitive impairments, mainly affecting executive functioning, attention and episodic memory. Little is known about potential treatments of these cognitive deficits. The purpose of this study was to evaluate the effects of a process-based cognitive training intervention, designed to target the specific cognitive impairments associated with stress-related exhaustion. To this end, patients diagnosed with exhaustion disorder (ED) were randomized to either a multimodal stress rehabilitation program with the addition of a process-based cognitive training intervention (training group, n = 27) or a treatment-as-usual control condition, consisting of multimodal stress rehabilitation with no additional training (control group, n = 32). Treatment effects were evaluated through an extensive cognitive test battery, assessing both near and far transfer effects, as well as self-report forms regarding subjective cognitive complaints and burnout levels. Results showed pronounced training-related improvements on the criterion updating task (p < 0.001). Further, evidence was found of selective near transfer effects to updating (p = 0.01) and episodic memory (p = 0.04). Also, the trained group reported less subjective memory complaints (p = 0.02) and levels of burnout decreased for both groups, but more so for the trained group (p = 0.04), following the intervention. These findings suggest that process-based cognitive training may be a viable method to address the cognitive impairments associated with ED. PMID- 26270890 TI - Photolysis study of fluorinated ketones under natural sunlight conditions. AB - UV-visible absorption cross-sections are reported for CF3C(O)CH3, CF3C(O)CH2CH3, and CH3CH2C(O)CH(CH3)2. The photolysis rate constants of CF3C(O)CH3, CF3C(O)CH2CH3, and CF3CF2C(O)CF(CF3)2 were measured from smog-chamber experiments carried out in a 400 L Teflon-bag reactor under sunlight irradiation. Actinic radiation profiles from the "Tropospheric Ultraviolet and Visible Radiation Model" were used to obtain quantum efficiencies of photolysis: 0.34 +/- 0.08, 0.24 +/- 0.06, and (4.4 +/- 0.6) * 10(-2) for CF3C(O)CH3, CF3C(O)CH2CH3, and CF3CF2C(O)CF(CF3)2, respectively. These values correspond to wavelength ranges of 295-345 nm (for CF3C(O)CH3 and CF3C(O)CH2CH3) and 295-360 nm (for CF3CF2C(O)CF(CF3)2). The photolysis rate constants change significantly with the seasons, with the yearly averages being (2.3 +/- 0.7) * 10(-6), (1.8 +/- 0.6) * 10(-6), and (2.1 +/- 0.8) * 10(-6) s(-1) for CF3C(O)CH3, CF3C(O)CH2CH3, and CF3CF2C(O)CF(CF3)2, respectively. Photolysis processes are fast and responsible for the short gas-phase lifetimes of the studied ketones, which are 5.1 +/- 2.2, 6.5 +/- 2.5 and 5.5 +/- 1.5 days. The radiative forcing efficiencies are provided to assess the contribution of emissions of these gases to climate change. As a result of the short atmospheric lifetimes, their global warming potentials are negligible. Theoretical calculations involving ground and excited states justify the higher photolysis quantum efficiencies of CF3C(O)CH3 and CF3C(O)CH2CH3 compared to CF3CF2C(O)CF(CF3)2, which shows increased photolysis rate constants in the absence of O2. PMID- 26270891 TI - Interventions for treating fractures of the distal femur in adults. AB - BACKGROUND: Fractures of the distal femur (the part of the thigh bone nearest the knee) are a considerable cause of morbidity. Various different surgical and non surgical treatments have been used in the management of these injuries but the best treatment remains controversial. OBJECTIVES: To assess the effects (benefits and harms) of interventions for treating fractures of the distal femur in adults. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (9 September 2014); the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2014, Issue 8); MEDLINE (1946 to August week 4 2014); EMBASE (1980 to 2014 week 36); World Health Organization (WHO) International Clinical Trials Registry Platform (January 2015); conference proceedings and reference lists without language restrictions. SELECTION CRITERIA: Randomised and quasi-randomised controlled clinical trials comparing interventions for treating fractures of the distal femur in adults. Our primary outcomes were patient-reported outcome measures (PROMs) of knee function and adverse events, including re-operations. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and performed data extraction and risk of bias assessment. We assessed treatment effects using risk ratios (RR) or mean differences (MD) and, where appropriate, we pooled data using a fixed-effect model. MAIN RESULTS: We included seven studies that involved a total of 444 adults with distal femur fractures. Each of the included studies was small and assessed to be at substantial risk of bias, with four studies being quasi randomised and none of the studies using blinding in outcome assessment. All studies provided an incomplete picture of outcome. Based on GRADE criteria, we assessed the quality of the evidence as very low for all reported outcomes, which means we are very uncertain of the reliability of these results.One study compared surgical (dynamic condylar screw (DCS) fixation) and non-surgical (skeletal traction) treatment in 42 older adults (mean age 79 years) with displaced fractures of the distal femur. This study, which did not report on PROMs, provided very low quality evidence of little between-group differences in adverse events such as death (2/20 surgical versus 1/20 non-surgical), re operation or repeat procedures (1/20 versus 3/20) and other adverse effects including delayed union. However, while none of the findings were statistically significant, there were more complications such as pressure sores (0/20 versus 4/20) associated with prolonged immobilisation in the non-surgical group, who stayed on average one month longer in hospital.The other six studies compared different surgical interventions. Three studies, including 159 participants, compared retrograde intramedullary nail (RIMN) fixation versus DCS or blade-plate fixation (fixed-angle devices). None of these studies reported PROMS relating to function. None of the results for the reported adverse events showed a difference between the two implants. Thus, although there was very low quality evidence of a higher risk of re-operation in the RIMN group, the 95% confidence interval (CI) also included the possibility of a higher risk of re-operation for the fixed angle device (9/83 RIMN versus 4/96 fixed-angle device; 3 studies: RR 1.85, 95% CI 0.62 to 5.57). There was no clinically important difference between the two groups found in quality of life assessed using the 36-item Short Form in one study (23 fractures).One study (18 participants) provided very low quality evidence of there being little difference in adverse events between RIMN and non locking plate fixation. One study (53 participants) provided very low quality evidence of a higher risk of re-operation after locking plate fixation compared with a single fixed-angle device (6/28 locking plate versus 1/25 fixed-angle device; RR 5.36, 95% CI 0.69 to 41.50); however, the 95% CI also included the possibility of a higher risk of re-operation for the fixed-angle device. Neither of these trials reported on PROMs.The largest included study, which reported outcomes in 126 participants at one-year follow-up, compared RIMN versus locking plate fixation; both implants are commonly used in current practice. None of the between-group differences in the reported outcomes were statistically significant; thus the CIs crossed the line of no effect. There was very low quality evidence of better patient-reported musculoskeletal function in the RIMN group based on Short Musculoskeletal Function Assessment (0 to 100: best function) scores (e.g. dysfunction index: MD -5.90 favouring RIMN, 95% CI -15.13 to 3.33) as well as quality of life using the EuroQoL-5D Index (0 to 1: best quality of life) (MD 0.10 favouring RIMN, 95% CI -0.01 to 0.21). The CIs for both results included a clinically important effect favouring RIMN but also a clinically insignificant effect in favour of locking plate fixation. AUTHORS' CONCLUSIONS: This review highlights the major limitations of the available evidence concerning current treatment interventions for fractures of the distal femur. The currently available evidence is incomplete and insufficient to inform current clinical practice. Priority should be given to a definitive, pragmatic, multicentre randomised controlled clinical trial comparing contemporary treatments such as locked plates and intramedullary nails. At minimum, these should report validated patient-reported functional and quality-of-life outcomes at one and two years. All trials should be reported in full using the CONSORT guidelines. PMID- 26270892 TI - Genotoxicity of three food processing contaminants in transgenic mice expressing human sulfotransferases 1A1 and 1A2 as assessed by the in vivo alkaline single cell gel electrophoresis assay. AB - The food processing contaminants 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 5-hydroxymethylfurfural (HMF) and 2,5 dimethylfuran (DMF) are potentially both mutagenic and carcinogenic in vitro and/or in vivo, although data on DMF is lacking. The PHIP metabolite N-hydroxy-PhIP and HMF are bioactivated by sulfotransferases (SULTs). The substrate specificity and tissue distribution of SULTs differs between species. A single oral dose of PhIP, HMF or DMF was administered to wild-type (wt) mice and mice expressing human SULT1A1/1A2 (hSULT mice). DNA damage was studied using the in vivo alkaline single cell gel electrophoresis (SCGE) assay. No effects were detected in wt mice. In the hSULT mice, PhIP and HMF exposure increased the levels of DNA damage in the liver and kidney, respectively. DMF was not found to be genotoxic. The observation of increased DNA damage in hSULT mice compared with wt mice supports the role of human SULTs in the bioactivation of N-hydroxy-PhIP and HMF in vivo. PMID- 26270893 TI - Highly Enhanced Fluorescence of CdSeTe Quantum Dots Coated with Polyanilines via In-Situ Polymerization and Cell Imaging Application. AB - The polyaniline (PAN)-coated CdSeTe quantum dots (QDs) were prepared by in situ polymerization of aniline on the surface of CdSeTe QDs. The PAN-coated CdSeTe QDs has a tremendously enhanced fluorescence (~40 times) and improved biocompatibility compared to the uncoated CdSeTe QDs. The fluorescence intensity of the PAN-coated CdSeTe QDs can be adjusted by controlling the construction parameters of the PAN shell. The kinetics of the in situ controllable polymerization process was studied by varying the temperature, and the apparent activation energy of polymerization was estimated. With the same method, a series of the PAN derivatives were also tested to coat the CdSeTe QDs in this study. All the QDs showed a significant enhancement of the fluorescence intensity and better biocompatibility. The significantly enhanced fluorescence can provide highly amplified signal for luminescence-based cell imaging. PMID- 26270894 TI - Outer-Sphere Electrophilic Fluorination of Organometallic Complexes. AB - Organofluorine chemistry plays a key role in materials science, pharmaceuticals, agrochemicals, and medical imaging. However, the formation of new carbon-fluorine bonds with controlled regiochemistry and functional group tolerance is synthetically challenging. The use of metal complexes to promote fluorination reactions is of great current interest, but even state-of-the-art approaches are limited in their substrate scope, often require activated substrates, or do not allow access to desirable functionality, such as alkenyl C(sp(2))-F or chiral C(sp(3))-F centers. Here, we report the formation of new alkenyl and alkyl C-F bonds in the coordination sphere of ruthenium via an unprecedented outer-sphere electrophilic fluorination mechanism. The organometallic species involved are derived from nonactivated substrates (pyridine and terminal alkynes), and C-F bond formation occurs with full regio- and diastereoselectivity. The fluorinated ligands that are formed are retained at the metal, which allows subsequent metal mediated reactivity. PMID- 26270895 TI - Response to Comment on "UV Disinfection Induces a VBNC State in Escherichia coli and Pseudomonas aeruginosa". PMID- 26270896 TI - Getting Hot Under the CALR: What Drives Pediatric Myeloproliferative Neoplasms? PMID- 26270897 TI - Correlation of expertise with error detection skills of force application during spinal manipulation learning. AB - OBJECTIVE: Most studies on spinal manipulation learning demonstrate the relevance of including motor learning strategies in chiropractic curricula. Two outcomes of practice are the production of movement in an efficient manner and the improved capability of learners to evaluate their own motor performance. The goals of this study were to evaluate if expertise is associated with increased spinal manipulation proficiency and if error detection skills of force application during a high-velocity low-amplitude spinal manipulation are related to expertise. METHODS: Three groups of students and 1 group of expert chiropractors completed 10 thoracic spine manipulations on an instrumented device with the specific goal of reaching a maximum peak force of 300 N after a brief period of practice. After each trial, participants were asked to give an estimate of their maximal peak force. Force-time profiles were analyzed to determine the biomechanical parameters of each participant and the participant's capacity to estimate his or her own performance. RESULTS: Significant between-group differences were found for each biomechanical parameter. No significant difference was found between groups for the error detection variables (p > .05). The lack of significant effects related to the error detection capabilities with expertise could be related to the specificity of the task and how the training process was structured. CONCLUSION: This study confirms that improvements in biomechanical parameters of spinal manipulation are related to expertise. Feedback based on error detection could be implemented in chiropractic curricula to improve trainee abilities in detecting motor execution errors. PMID- 26270899 TI - Role of radiation therapy in primary mediastinal large B-cell lymphoma in rituximab era: A US population-based analysis. AB - The use of radiation (RT) in primary mediastinal large B-cell lymphoma (PMBCL) may predispose young patients to the risk of cardiopulmonary toxicities and secondary malignancies. We used Surveillance, Epidemiology and End Results (SEER) 18 database to compare the overall survival (OS) differences among adult patients treated with and without RT after rituximab approval in the US. Multivariate analyses were performed using Cox proportional hazards regression to compare OS based on the use of RT while adjusting for age, year of diagnosis, race, stage and gender. PMBCL patients (n = 258), who received RT (48%), were similar in terms of age, gender, race, and stage at diagnosis to patients who did not receive RT. The five year OS was similar between patients treated with versus without RT (82.5% vs. 78.6%, P = 0.47). In a multivariate analysis, the use of RT did not influence OS in the rituximab era (HR 0.83; 95% CI 0.43-1.59; P = 0.56). Rituximab may reduce the benefit of RT in select patients such as those who achieve a metabolic complete remission at the end of chemotherapy. PMID- 26270900 TI - Discussion: An Argument for Salvage in Severe Lower Extremity Trauma with Posterior Tibial Nerve Injury: The Ganga Hospital Experience. PMID- 26270898 TI - Combination Growth Factor Therapy via Electrostatically Assembled Wound Dressings Improves Diabetic Ulcer Healing In Vivo. AB - Chronic skin ulcerations are a common complication of diabetes mellitus, affecting up to one in four diabetic individuals. Despite the prevalence of these wounds, current pharmacologic options for treating them remain limited. Growth factor-based therapies have displayed a mixed ability to drive successful healing, which may be due to nonoptimal delivery strategies. Here, a method for coating commercially available nylon dressings using the layer-by-layer process is described to enable both sustained release and independent control over the release kinetics of vascular endothelial growth factor 165 and platelet-derived growth factor BB. It is shown that the use of strategically spaced diffusion barriers formed spontaneously by disulfide bonds enables independent control over the release rates of incorporated growth factors, and that in vivo these dressings improve several aspects of wound healing in db/db mice. PMID- 26270901 TI - The Current State of Global Surgery Training in Plastic Surgery Residency. AB - BACKGROUND: The current state of global surgery training in U.S. plastic surgery residency programs remains largely undefined. METHODS: An electronic survey was distributed to Accreditation Council for Graduate Medical Education-certified plastic surgery residency programs. Programs with global health curricula were queried regarding classification, collaboration details, regions visited, conditions/procedures encountered, costs, accreditation, and personal sentiment. Residencies without global health curricula were asked to select barriers. RESULTS: Sixty-four of 81 residency programs returned questionnaires (response rate, 79 percent). Twenty-six programs (41 percent) reported including a formal global health curriculum; 38 did not (59 percent). When asked to classify this curriculum, most selected clinical care experience [n = 24 (92 percent)], followed by educational experience [n = 19 (73 percent)]. Personal reference was the most common means of establishing the international collaboration [n = 19 (73 percent)]. The most commonly encountered conditions were cleft lip-cleft palate [n = 26 (100 percent)], thermal injury [n = 17 (65 percent)], and posttraumatic reconstruction [n = 15 (57 percent)]. Dominant funding sources were primarily nonprofit organizations [n = 14 (53 percent)]. Although the majority of programs had not applied for residency review committee accreditation [n = 23 (88 percent)], many considered applying [n = 16 (62 percent)]. Overall, 96 percent of programs (n = 25) supported global health training in residency, choosing exposure to different health systems [n = 22 (88 percent)] and surgical education [n = 17 (68 percent)] as reasons. Programs not offering a global health experience most commonly reported lack of residency review committee/plastic surgery operative log recognition of cases performed abroad [n = 27 (71 percent)], funding for trip expenses [n = 25 (66 percent)], and salary support [n = 24 (63 percent)] as barriers. CONCLUSIONS: Residencies incorporating global health training describe the experience positively. Funding and case accreditation are the major obstacles to implementing these curricula. PMID- 26270902 TI - An Argument for Salvage in Severe Lower Extremity Trauma with Posterior Tibial Nerve Injury: The Ganga Hospital Experience. AB - BACKGROUND: Absence of plantar sensation is a critical factor considered in favor of amputation for patients with lower limb-threatening injuries. This study aims to assess outcomes of limb salvage in a group of patients with severe lower extremity injuries associated with posterior tibial nerve transection. METHODS: The authors studied eight cases of limb salvage after traumatic injuries with documented tibial nerve laceration managed at Ganga Hospital, India. Functional and health-related quality-of-life outcomes were assessed. Outcomes from this case series were compared to outcomes of studies from a systematic literature review on salvage of the severely injured lower extremity. RESULTS: Patients in this case series reported mild pain (median score, 20 on a visual analogue scale ranging from 0 to 100), with some return of plantar sensation in patients with tibial nerve repairs (median score, 2 of 5). Patients demonstrated a decrease in ankle motion (27.5 degrees' plantar flexion and 10 degrees' extension) and muscle strength (median heel flexor score, 3 of 5). All patients could ambulate independently. Quality of life and function measured by validated instruments revealed minimal disability. The authors identified 1767 articles on lower extremity trauma, and 14 articles were reviewed systematically. Relative to the case series, published articles reported similarly diminished ankle motion and muscle strength, with reports of mild pain in select studies. Patient-reported outcomes instruments found variations in the degree of physical disability based on the time from injury. CONCLUSION: Although limited in number, this case series demonstrates the value of limb salvage even for patients with posterior tibial nerve injury. PMID- 26270905 TI - On the Spectrum of the Plenoptic Function. AB - The plenoptic function is a powerful tool to analyze the properties of multi-view image data sets. In particular, the understanding of the spectral properties of the plenoptic function is essential in many computer vision applications, including image-based rendering. In this paper, we derive for the first time an exact closed-form expression of the plenoptic spectrum of a slanted plane with finite width and use this expression as the elementary building block to derive the plenoptic spectrum of more sophisticated scenes. This is achieved by approximating the geometry of the scene with a set of slanted planes and evaluating the closed-form expression for each plane in the set. We then use this closed-form expression to revisit uniform plenoptic sampling. In this context, we derive a new Nyquist rate for the plenoptic sampling of a slanted plane and a new reconstruction filter. Through numerical simulations, on both real and synthetic scenes, we show that the new filter outperforms alternative existing filters. PMID- 26270904 TI - Nanotheranostics: Congo Red/Rutin-MNPs with Enhanced Magnetic Resonance Imaging and H2O2-Responsive Therapy of Alzheimer's Disease in APPswe/PS1dE9 Transgenic Mice. AB - As nanotheranostics, Congo red/Rutin-MNPs combine the abilities of diagnosis and treatment of Alzheimer's disease (AD). The biocompatible nanotheranostics system based on iron oxide magnetic nanoparticles, with ultrasmall size and excellent magnetic properties, can specifically detect amyloid plaques by magnetic resonance imaging, realize targeted delivery of AD therapeutic agents, achieve drug controlled release by H2O2 response, and prevent oxidative stress. PMID- 26270906 TI - Visual Typo Correction by Collocative Optimization: A Case Study on Merchandize Images. AB - Near-duplicate retrieval (NDR) in merchandize images is of great importance to a lot of online applications on e-Commerce websites. In those applications where the requirement of response time is critical, however, the conventional techniques developed for a general purpose NDR are limited, because expensive post-processing like spatial verification or hashing is usually employed to compromise the quantization errors among the visual words used for the images. In this paper, we argue that most of the errors are introduced because of the quantization process where the visual words are considered individually, which has ignored the contextual relations among words. We propose a "spelling or phrase correction" like process for NDR, which extends the concept of collocations to visual domain for modeling the contextual relations. Binary quadratic programming is used to enforce the contextual consistency of words selected for an image, so that the errors (typos) are eliminated and the quality of the quantization process is improved. The experimental results show that the proposed method can improve the efficiency of NDR by reducing vocabulary size by 1000% times, and under the scenario of merchandize image NDR, the expensive local interest point feature used in conventional approaches can be replaced by color moment feature, which reduces the time cost by 9202% while maintaining comparable performance to the state-of-the-art methods. PMID- 26270907 TI - Large Discriminative Structured Set Prediction Modeling With Max-Margin Markov Network for Lossless Image Coding. AB - Inherent statistical correlation for context-based prediction and structural interdependencies for local coherence is not fully exploited in existing lossless image coding schemes. This paper proposes a novel prediction model where the optimal correlated prediction for a set of pixels is obtained in the sense of the least code length. It not only exploits the spatial statistical correlations for the optimal prediction directly based on 2D contexts, but also formulates the data-driven structural interdependencies to make the prediction error coherent with the underlying probability distribution for coding. Under the joint constraints for local coherence, max-margin Markov networks are incorporated to combine support vector machines structurally to make max-margin estimation for a correlated region. Specifically, it aims to produce multiple predictions in the blocks with the model parameters learned in such a way that the distinction between the actual pixel and all possible estimations is maximized. It is proved that, with the growth of sample size, the prediction error is asymptotically upper bounded by the training error under the decomposable loss function. Incorporated into the lossless image coding framework, the proposed model outperforms most prediction schemes reported. PMID- 26270908 TI - Tree Filtering: Efficient Structure-Preserving Smoothing With a Minimum Spanning Tree. AB - We present a new efficient edge-preserving filter-"tree filter"-to achieve strong image smoothing. The proposed filter can smooth out high-contrast details while preserving major edges, which is not achievable for bilateral-filter-like techniques. Tree filter is a weighted-average filter, whose kernel is derived by viewing pixel affinity in a probabilistic framework simultaneously considering pixel spatial distance, color/intensity difference, as well as connectedness. Pixel connectedness is acquired by treating pixels as nodes in a minimum spanning tree (MST) extracted from the image. The fact that an MST makes all image pixels connected through the tree endues the filter with the power to smooth out high contrast, fine-scale details while preserving major image structures, since pixels in small isolated region will be closely connected to surrounding majority pixels through the tree, while pixels inside large homogeneous region will be automatically dragged away from pixels outside the region. The tree filter can be separated into two other filters, both of which turn out to have fast algorithms. We also propose an efficient linear time MST extraction algorithm to further improve the whole filtering speed. The algorithms give tree filter a great advantage in low computational complexity (linear to number of image pixels) and fast speed: it can process a 1-megapixel 8-bit image at ~ 0.25 s on an Intel 3.4 GHz Core i7 CPU (including the construction of MST). The proposed tree filter is demonstrated on a variety of applications. PMID- 26270909 TI - Action Recognition Using Nonnegative Action Component Representation and Sparse Basis Selection. AB - In this paper, we propose using high-level action units to represent human actions in videos and, based on such units, a novel sparse model is developed for human action recognition. There are three interconnected components in our approach. First, we propose a new context-aware spatial-temporal descriptor, named locally weighted word context, to improve the discriminability of the traditionally used local spatial-temporal descriptors. Second, from the statistics of the context-aware descriptors, we learn action units using the graph regularized nonnegative matrix factorization, which leads to a part-based representation and encodes the geometrical information. These units effectively bridge the semantic gap in action recognition. Third, we propose a sparse model based on a joint l2,1-norm to preserve the representative items and suppress noise in the action units. Intuitively, when learning the dictionary for action representation, the sparse model captures the fact that actions from the same class share similar units. The proposed approach is evaluated on several publicly available data sets. The experimental results and analysis clearly demonstrate the effectiveness of the proposed approach. PMID- 26270910 TI - Modeling Geometric-Temporal Context With Directional Pyramid Co-Occurrence for Action Recognition. AB - In this paper, we present a new geometric-temporal representation for visual action recognition based on local spatio-temporal features. First, we propose a modified covariance descriptor under the log-Euclidean Riemannian metric to represent the spatio-temporal cuboids detected in the video sequences. Compared with previously proposed covariance descriptors, our descriptor can be measured and clustered in Euclidian space. Second, to capture the geometric-temporal contextual information, we construct a directional pyramid co-occurrence matrix (DPCM) to describe the spatio-temporal distribution of the vector-quantized local feature descriptors extracted from a video. DPCM characterizes the co-occurrence statistics of local features as well as the spatio-temporal positional relationships among the concurrent features. These statistics provide strong descriptive power for action recognition. To use DPCM for action recognition, we propose a directional pyramid co-occurrence matching kernel to measure the similarity of videos. The proposed method achieves the state-of-the-art performance and improves on the recognition performance of the bag-of-visual words (BOVWs) models by a large margin on six public data sets. For example, on the KTH data set, it achieves 98.78% accuracy while the BOVW approach only achieves 88.06%. On both Weizmann and UCF CIL data sets, the highest possible accuracy of 100% is achieved. PMID- 26270911 TI - Gradient Magnitude Similarity Deviation: A Highly Efficient Perceptual Image Quality Index. AB - It is an important task to faithfully evaluate the perceptual quality of output images in many applications, such as image compression, image restoration, and multimedia streaming. A good image quality assessment (IQA) model should not only deliver high quality prediction accuracy, but also be computationally efficient. The efficiency of IQA metrics is becoming particularly important due to the increasing proliferation of high-volume visual data in high-speed networks. We present a new effective and efficient IQA model, called gradient magnitude similarity deviation (GMSD). The image gradients are sensitive to image distortions, while different local structures in a distorted image suffer different degrees of degradations. This motivates us to explore the use of global variation of gradient based local quality map for overall image quality prediction. We find that the pixel-wise gradient magnitude similarity (GMS) between the reference and distorted images combined with a novel pooling strategy the standard deviation of the GMS map-can predict accurately perceptual image quality. The resulting GMSD algorithm is much faster than most state-of-the-art IQA methods, and delivers highly competitive prediction accuracy. MATLAB source code of GMSD can be downloaded at http://www4.comp.polyu.edu.hk/~cslzhang/IQA/GMSD/GMSD.htm. PMID- 26270912 TI - Recognizing Gaits Across Views Through Correlated Motion Co-Clustering. AB - Human gait is an important biometric feature, which can be used to identify a person remotely. However, view change can cause significant difficulties for gait recognition because it will alter available visual features for matching substantially. Moreover, it is observed that different parts of gait will be affected differently by view change. By exploring relations between two gaits from two different views, it is also observed that a part of gait in one view is more related to a typical part than any other parts of gait in another view. A new method proposed in this paper considers such variance of correlations between gaits across views that is not explicitly analyzed in the other existing methods. In our method, a novel motion co-clustering is carried out to partition the most related parts of gaits from different views into the same group. In this way, relationships between gaits from different views will be more precisely described based on multiple groups of the motion co-clustering instead of a single correlation descriptor. Inside each group, a linear correlation between gait information across views is further maximized through canonical correlation analysis (CCA). Consequently, gait information in one view can be projected onto another view through a linear approximation under the trained CCA subspaces. In the end, a similarity between gaits originally recorded from different views can be measured under the approximately same view. Comprehensive experiments based on widely adopted gait databases have shown that our method outperforms the state-of the-art. PMID- 26270913 TI - Image Quality Assessment for Fake Biometric Detection: Application to Iris, Fingerprint, and Face Recognition. AB - To ensure the actual presence of a real legitimate trait in contrast to a fake self-manufactured synthetic or reconstructed sample is a significant problem in biometric authentication, which requires the development of new and efficient protection measures. In this paper, we present a novel software-based fake detection method that can be used in multiple biometric systems to detect different types of fraudulent access attempts. The objective of the proposed system is to enhance the security of biometric recognition frameworks, by adding liveness assessment in a fast, user-friendly, and non-intrusive manner, through the use of image quality assessment. The proposed approach presents a very low degree of complexity, which makes it suitable for real-time applications, using 25 general image quality features extracted from one image (i.e., the same acquired for authentication purposes) to distinguish between legitimate and impostor samples. The experimental results, obtained on publicly available data sets of fingerprint, iris, and 2D face, show that the proposed method is highly competitive compared with other state-of-the-art approaches and that the analysis of the general image quality of real biometric samples reveals highly valuable information that may be very efficiently used to discriminate them from fake traits. PMID- 26270914 TI - Band-Reweighed Gabor Kernel Embedding for Face Image Representation and Recognition. AB - Face recognition with illumination or pose variation is a challenging problem in image processing and pattern recognition. A novel algorithm using band-reweighed Gabor kernel embedding to deal with the problem is proposed in this paper. For a given image, it is first transformed by a group of Gabor filters, which output Gabor features using different orientation and scale parameters. Fisher scoring function is used to measure the importance of features in each band, and then, the features with the largest scores are preserved for saving memory requirements. The reduced bands are combined by a vector, which is determined by a weighted kernel discriminant criterion and solved by a constrained quadratic programming method, and then, the weighted sum of these nonlinear bands is defined as the similarity between two images. Compared with existing concatenation-based Gabor feature representation and the uniformly weighted similarity calculation approaches, our method provides a new way to use Gabor features for face recognition and presents a reasonable interpretation for highlighting discriminant orientations and scales. The minimum Mahalanobis distance considering the spatial correlations within the data is exploited for feature matching, and the graphical lasso is used therein for directly estimating the sparse inverse covariance matrix. Experiments using benchmark databases show that our new algorithm improves the recognition results and obtains competitive performance. PMID- 26270915 TI - Multilinear Graph Embedding: Representation and Regularization for Images. AB - Given a set of images, finding a compact and discriminative representation is still a big challenge especially when multiple latent factors are hidden in the way of data generation. To represent multifactor images, although multilinear models are widely used to parameterize the data, most methods are based on high order singular value decomposition (HOSVD), which preserves global statistics but interprets local variations inadequately. To this end, we propose a novel method, called multilinear graph embedding (MGE), as well as its kernelization MKGE to leverage the manifold learning techniques into multilinear models. Our method theoretically links the linear, nonlinear, and multilinear dimensionality reduction. We also show that the supervised MGE encodes informative image priors for image regularization, provided that an image is represented as a high-order tensor. From our experiments on face and gait recognition, the superior performance demonstrates that MGE better represents multifactor images than classic methods, including HOSVD and its variants. In addition, the significant improvement in image (or tensor) completion validates the potential of MGE for image regularization. PMID- 26270916 TI - Global Image Denoising. AB - Most existing state-of-the-art image denoising algorithms are based on exploiting similarity between a relatively modest number of patches. These patch-based methods are strictly dependent on patch matching, and their performance is hamstrung by the ability to reliably find sufficiently similar patches. As the number of patches grows, a point of diminishing returns is reached where the performance improvement due to more patches is offset by the lower likelihood of finding sufficiently close matches. The net effect is that while patch-based methods, such as BM3D, are excellent overall, they are ultimately limited in how well they can do on (larger) images with increasing complexity. In this paper, we address these shortcomings by developing a paradigm for truly global filtering where each pixel is estimated from all pixels in the image. Our objectives in this paper are two-fold. First, we give a statistical analysis of our proposed global filter, based on a spectral decomposition of its corresponding operator, and we study the effect of truncation of this spectral decomposition. Second, we derive an approximation to the spectral (principal) components using the Nystrom extension. Using these, we demonstrate that this global filter can be implemented efficiently by sampling a fairly small percentage of the pixels in the image. Experiments illustrate that our strategy can effectively globalize any existing denoising filters to estimate each pixel using all pixels in the image, hence improving upon the best patch-based methods. PMID- 26270917 TI - Background-Modeling-Based Adaptive Prediction for Surveillance Video Coding. AB - The exponential growth of surveillance videos presents an unprecedented challenge for high-efficiency surveillance video coding technology. Compared with the existing coding standards that were basically developed for generic videos, surveillance video coding should be designed to make the best use of the special characteristics of surveillance videos (e.g., relative static background). To do so, this paper first conducts two analyses on how to improve the background and foreground prediction efficiencies in surveillance video coding. Following the analysis results, we propose a background-modeling-based adaptive prediction (BMAP) method. In this method, all blocks to be encoded are firstly classified into three categories. Then, according to the category of each block, two novel inter predictions are selectively utilized, namely, the background reference prediction (BRP) that uses the background modeled from the original input frames as the long-term reference and the background difference prediction (BDP) that predicts the current data in the background difference domain. For background blocks, the BRP can effectively improve the prediction efficiency using the higher quality background as the reference; whereas for foreground-background hybrid blocks, the BDP can provide a better reference after subtracting its background pixels. Experimental results show that the BMAP can achieve at least twice the compression ratio on surveillance videos as AVC (MPEG-4 Advanced Video Coding) high profile, yet with a slightly additional encoding complexity. Moreover, for the foreground coding performance, which is crucial to the subjective quality of moving objects in surveillance videos, BMAP also obtains remarkable gains over several state-of-the-art methods. PMID- 26270918 TI - Robust Online Learned Spatio-Temporal Context Model for Visual Tracking. AB - Visual tracking is an important but challenging problem in the computer vision field. In the real world, the appearances of the target and its surroundings change continuously over space and time, which provides effective information to track the target robustly. However, enough attention has not been paid to the spatio-temporal appearance information in previous works. In this paper, a robust spatio-temporal context model based tracker is presented to complete the tracking task in unconstrained environments. The tracker is constructed with temporal and spatial appearance context models. The temporal appearance context model captures the historical appearance of the target to prevent the tracker from drifting to the background in a long-term tracking. The spatial appearance context model integrates contributors to build a supporting field. The contributors are the patches with the same size of the target at the key-points automatically discovered around the target. The constructed supporting field provides much more information than the appearance of the target itself, and thus, ensures the robustness of the tracker in complex environments. Extensive experiments on various challenging databases validate the superiority of our tracker over other state-of-the-art trackers. PMID- 26270919 TI - Compressed-Domain Video Retargeting. AB - In this paper, we present a compressed-domain video retargeting solution that operates without compromising the resizing quality. Existing video retargeting methods operate in the spatial (or pixel) domain. Such a solution is not practical if it is implemented in mobile devices due to its large memory requirement. In the proposed solution, each component of the retargeting system is designed to exploit the low-level compressed domain features extracted from the coded bit stream. For example, motion information is obtained directly from motion vectors. An efficient column shape mesh deformation is employed to solve the difficulty of sophisticated quad-shape mesh deformation in the compressed domain. The proposed solution achieves comparable (or slightly better) visual quality performance as compared with several state-of-the-art pixel-domain retargeting methods at lower computational and memory costs, making content-aware video resizing both scalable and practical in real-world applications. PMID- 26270920 TI - Latent Hierarchical Model of Temporal Structure for Complex Activity Classification. AB - Modeling the temporal structure of sub-activities is an important yet challenging problem in complex activity classification. This paper proposes a latent hierarchical model (LHM) to describe the decomposition of complex activity into sub-activities in a hierarchical way. The LHM has a tree-structure, where each node corresponds to a video segment (sub-activity) at certain temporal scale. The starting and ending time points of each sub-activity are represented by two latent variables, which are automatically determined during the inference process. We formulate the training problem of the LHM in a latent kernelized SVM framework and develop an efficient cascade inference method to speed up classification. The advantages of our methods come from: 1) LHM models the complex activity with a deep structure, which is decomposed into sub-activities in a coarse-to-fine manner and 2) the starting and ending time points of each segment are adaptively determined to deal with the temporal displacement and duration variation of sub-activity. We conduct experiments on three datasets: 1) the KTH; 2) the Hollywood2; and 3) the Olympic Sports. The experimental results show the effectiveness of the LHM in complex activity classification. With dense features, our LHM achieves the state-of-the-art performance on the Hollywood2 dataset and the Olympic Sports dataset. PMID- 26270921 TI - mCENTRIST: A Multi-Channel Feature Generation Mechanism for Scene Categorization. AB - mCENTRIST, a new multichannel feature generation mechanism for recognizing scene categories, is proposed in this paper. mCENTRIST explicitly captures the image properties that are encoded jointly by two image channels, which is different from popular multichannel descriptors. In order to avoid the curse of dimensionality, tradeoffs at both feature and channel levels have been executed to make mCENTRIST computationally practical. As a result, mCENTRIST is both efficient and easy to implement. In addition, a hyperopponent color space is proposed by embedding Sobel information into the opponent color space for further performance improvements. Experiments show that mCENTRIST outperforms established multichannel descriptors on four RGB and RGB-near infrared data sets, including aerial orthoimagery, indoor, and outdoor scene category recognition tasks. Experiments also verify that the hyper opponent color space enhances descriptors' performance effectively. PMID- 26270922 TI - Scaled Heavy-Ball Acceleration of the Richardson-Lucy Algorithm for 3D Microscopy Image Restoration. AB - The Richardson-Lucy algorithm is one of the most important in image deconvolution. However, a drawback is its slow convergence. A significant acceleration was obtained using the technique proposed by Biggs and Andrews (BA), which is implemented in the deconvlucy function of the image processing MATLAB toolbox. The BA method was developed heuristically with no proof of convergence. In this paper, we introduce the heavy-ball (H-B) method for Poisson data optimization and extend it to a scaled H-B method, which includes the BA method as a special case. The method has a proof of the convergence rate of O(K(-2)), where k is the number of iterations. We demonstrate the superior convergence performance, by a speedup factor of five, of the scaled H-B method on both synthetic and real 3D images. PMID- 26270923 TI - Enhanced Decoupled Active Contour Using Structural and Textural Variation Energy Functionals. AB - Active contours are a popular approach for object segmentation that uses an energy minimizing spline to extract an object's boundary. Nonparametric approaches can be computationally complex, whereas parametric approaches can be impacted by parameter sensitivity. A decoupled active contour (DAC) overcomes these problems by decoupling the external and internal energies and optimizing them separately. However a drawback of this approach is its reliance on the edge gradient as the external energy. This can lead to poor convergence toward the object boundary in the presence of weak object and strong background edges. To overcome these issues with convergence, a novel approach is proposed that takes advantage of a sparse texture model, which explicitly considers texture for boundary detection. The approach then defines the external energy as a weighted combination of textural and structural variation maps and feeds it into a multifunctional hidden Markov model for more robust object boundary detection. The enhanced DAC (EDAC) is qualitatively and visually analyzed on two natural image data sets as well as Brodatz images. The results demonstrate that EDAC effectively combines texture and structural information to extract the object boundary without impact on computation time and a reliance on color. PMID- 26270924 TI - Probability-Based Rendering for View Synthesis. AB - In this paper, a probability-based rendering (PBR) method is described for reconstructing an intermediate view with a steady-state matching probability (SSMP) density function. Conventionally, given multiple reference images, the intermediate view is synthesized via the depth image-based rendering technique in which geometric information (e.g., depth) is explicitly leveraged, thus leading to serious rendering artifacts on the synthesized view even with small depth errors. We address this problem by formulating the rendering process as an image fusion in which the textures of all probable matching points are adaptively blended with the SSMP representing the likelihood that points among the input reference images are matched. The PBR hence becomes more robust against depth estimation errors than existing view synthesis approaches. The MP in the steady state, SSMP, is inferred for each pixel via the random walk with restart (RWR). The RWR always guarantees visually consistent MP, as opposed to conventional optimization schemes (e.g., diffusion or filtering-based approaches), the accuracy of which heavily depends on parameters used. Experimental results demonstrate the superiority of the PBR over the existing view synthesis approaches both qualitatively and quantitatively. Especially, the PBR is effective in suppressing flicker artifacts of virtual video rendering although no temporal aspect is considered. Moreover, it is shown that the depth map itself calculated from our RWR-based method (by simply choosing the most probable matching point) is also comparable with that of the state-of-the-art local stereo matching methods. PMID- 26270925 TI - Topology-Preserving Rigid Transformation of 2D Digital Images. AB - We provide conditions under which 2D digital images preserve their topological properties under rigid transformations. We consider the two most common digital topology models, namely dual adjacency and well-composedness. This paper leads to the proposal of optimal preprocessing strategies that ensure the topological invariance of images under arbitrary rigid transformations. These results and methods are proved to be valid for various kinds of images (binary, gray-level, label), thus providing generic and efficient tools, which can be used in particular in the context of image registration and warping. PMID- 26270926 TI - Rotation-Covariant Texture Learning Using Steerable Riesz Wavelets. AB - We propose a texture learning approach that exploits local organizations of scales and directions. First, linear combinations of Riesz wavelets are learned using kernel support vector machines. The resulting texture signatures are modeling optimal class-wise discriminatory properties. The visualization of the obtained signatures allows verifying the visual relevance of the learned concepts. Second, the local orientations of the signatures are optimized to maximize their responses, which is carried out analytically and can still be expressed as a linear combination of the initial steerable Riesz templates. The global process is iteratively repeated to obtain final rotation-covariant texture signatures. Rapid convergence of class-wise signatures is observed, which demonstrates that the instances are projected into a feature space that leverages the local organizations of scales and directions. Experimental evaluation reveals average classification accuracies in the range of 97% to 98% for the Outex_TC_00010, the Outex_TC_00012, and the Contrib_TC_00000 suites for even orders of the Riesz transform, and suggests high robustness to changes in images orientation and illumination. The proposed framework requires no arbitrary choices of scales and directions and is expected to perform well in a large range of computer vision applications. PMID- 26270927 TI - Region-Based Iterative Reconstruction of Structurally Changing Objects in CT. AB - X-ray computed tomography (CT) is a powerful tool for noninvasive imaging of time varying objects. In the past, methods have been proposed to reconstruct images from continuously changing objects. For discretely or structurally changing objects, however, such methods fail to reconstruct high quality images, mainly because assumptions about continuity are no longer valid. In this paper, we propose a method to reconstruct structurally changing objects. Starting from the observation that there exist regions within the scanned object that remain unchanged over time, we introduce an iterative optimization routine that can automatically determine these regions and incorporate this knowledge in an algebraic reconstruction method. The proposed algorithm was validated on simulation data and experimental MUCT data, illustrating its capability to reconstruct structurally changing objects more accurately in comparison to current techniques. PMID- 26270928 TI - A General Exponential Framework for Dimensionality Reduction. AB - As a general framework, Laplacian embedding, based on a pairwise similarity matrix, infers low dimensional representations from high dimensional data. However, it generally suffers from three issues: 1) algorithmic performance is sensitive to the size of neighbors; 2) the algorithm encounters the well known small sample size (SSS) problem; and 3) the algorithm de-emphasizes small distance pairs. To address these issues, here we propose exponential embedding using matrix exponential and provide a general framework for dimensionality reduction. In the framework, the matrix exponential can be roughly interpreted by the random walk over the feature similarity matrix, and thus is more robust. The positive definite property of matrix exponential deals with the SSS problem. The behavior of the decay function of exponential embedding is more significant in emphasizing small distance pairs. Under this framework, we apply matrix exponential to extend many popular Laplacian embedding algorithms, e.g., locality preserving projections, unsupervised discriminant projections, and marginal fisher analysis. Experiments conducted on the synthesized data, UCI, and the Georgia Tech face database show that the proposed new framework can well address the issues mentioned above. PMID- 26270929 TI - Transmission Policy Selection for Multi-View Content Delivery Over Bandwidth Constrained Channels. AB - I formulate an optimization framework for computing the transmission actions of streaming multi-view video content over bandwidth constrained channels. The optimization finds the schedule for sending the packetized data that maximizes the reconstruction quality of the content, for the given network bandwidth. Two prospective multi-view content representation formats are considered: 1) MVC and 2) video plus depth. In the case of each, I formulate directed graph models that characterize the interdependencies between the data units that comprise the content. For the video plus depth format, I develop a novel space-time error concealment strategy that reconstructs the missing content based on received data units from multiple views. I design multiple techniques to solve the optimization problem of interest, at varying degrees of complexity and accuracy. In conjunction, I derive spatiotemporal models of the reconstruction error for the multi-view content that I employ to reduce the computational requirements of the optimization. I study the performance of my framework via simulation experiments. Significant gains in terms of rate-distortion efficiency are demonstrated over various reference methods. PMID- 26270930 TI - Comment on "Collinear Segment Detection Using HT Neighborhoods". AB - A novel application of the Hough transform (HT) neighborhood approach to collinear segment detection was proposed in [1]. It, however, suffered from one major weakness in that it could not provide an effective solution to the case of segment intersection. This paper analyzes a vital prerequisite step, disturbance elimination in the Hough space, and shows why, this method alone, is incapable of distinguishing the true segment endpoints. To address the problem, a unique HT butterfly separation method is proposed in this correspondence, as an essential complement to the above publication. PMID- 26270931 TI - Characteristics of Human Papillomavirus-Associated Head and Neck Cancers in a Veteran Population. AB - IMPORTANCE: The US veteran population represents a unique cohort of patients in whom human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) has yet to be investigated. OBJECTIVE: To investigate the incidence and characteristics of HPV-positive HNSCC within the veteran population. DESIGN, SETTING, AND PARTICIPANTS: Retrospective medical record review including patients with HNSCC diagnosed between January 1, 2010, and November 15, 2013, from the VA Greater Los Angeles Healthcare System. Data were collected between November 16, 2013, and June 19, 2014, and analyzed between June 20, 2014, and March 26, 2015. EXPOSURES: Chemoradiation therapy, radiation therapy, surgery, or no treatment. MAIN OUTCOMES AND MEASURES: We determined HPV positivity by p16 testing. Demographic and clinicopathologic information and overall survival were extracted from medical records. RESULTS: We identified 150 patients with the diagnosis of HNSCC. Sixty-nine patients had HPV-positive tumors (46%), and 65 (43%) had HPV negative tumors (16 did not have HPV testing). Age at diagnosis ranged from 44 to 94 years (mean, 64.6 [SD, 8.0] years), and median (interquartile range) follow-up was 16.7 (8.7-27.3) years. Tumor location differed significantly between the 2 groups, with an HPV-positive predominance in the oropharynx (43 of 57 [75%]; P < .001). The HPV-positive patients were more likely to be treated primarily with combined chemoradiation therapy than radiation therapy or surgery (P < .001). T4 tumors had a nearly 9 times greater rate of mortality compared with T1 tumors (HR, 8.52 [95% CI, 2.60-18.40; P < .001); N3 disease was associated with 7.18 times greater mortality (HR, 7.18 [95% CI, 1.99-12.26]; P < .001) compared with N1 disease; and M1 disease was associated with 6.0 times greater mortality (HR, 5.99 [95% CI, 2.59-13.81]; P < .001). There were 42 total deaths during follow up, 25 in the HPV-negative group and 17 in the HPV-positive group, with a nonsignificantly higher overall survival among HPV-positive patients independent of alcohol or tobacco use history (P = .09). CONCLUSIONS AND RELEVANCE: Previous studies have found that the proportion of HPV-positive HNSCC in the general population ranges between 20% and 75%. Although the incidence of HPV-positive HNSCC in the Veterans Affairs population is comparable, these patients have unique risk factors and demographic characteristics that may suggest different prognostic factors for HPV-positive HNSCC in this population. Nonetheless, HPV positive tumors still seem to portend a better overall prognosis regardless of alcohol or tobacco history among the Veterans Affairs population. PMID- 26270932 TI - College Women's Attributions of Blame for Experiences of Sexual Assault. AB - Little research has examined the factors that help to explain or predict different attributions of blame that rape survivors assign to their assault experiences. The current study sought to examine (a) rape survivors' attributions of blame to themselves and to external sources, specifically the perpetrator, the circumstances surrounding the assault (i.e., the situation), and society; (b) whether or not rape survivors attribute more blame to certain sources than others; and (c) which individual and situational factors that have been discussed in the sexual assault research literature help to explain self-blame, perpetrator blame, situational blame, and societal blame within a college sample ( N = 129). Results indicated that rape survivors attributed the most blame to themselves and to society, some blame to the situation, and the least blame to the male involved. Multiple regression analyses revealed that, for the most part, variables specific to the rape survivor (e.g., history of childhood sexual abuse, clarity of refusing sex, and perceived level of intoxication) significantly related to self-blame, whereas variables specific to assault severity significantly related to perpetrator blame (e.g., level of physical harm, type of rape, and recency of the assault), although in some unexpected ways. Age and recency of the assault were significantly related to situational blame. Clarity of refusing sex was the only variable that was significantly related to societal blame. Implications are discussed for prevention, education, and practice. PMID- 26270933 TI - The Impact of Childhood Abuse and Current Mental Health on Young Adult Intimate Relationship Functioning. AB - This study examines the association between childhood abuse and intimate relationship quality and attachment security in young adults. Data were drawn from the Ontario Child Health Study, a province-wide community-based survey that collected baseline data in 1983 from 3,294 children (aged 4 to 16 years) and follow-up data in 2000/2001 (then aged 21 to 35 years). The sample comprised 1,885 men and women who had completed questionnaires regarding retrospective accounts of childhood abuse and current relationship status in 2000/2001. Childhood physical and sexual abuse was assessed using the short form of the Childhood Experiences of Violence Questionnaire. It was hypothesized that childhood physical and sexual abuse would be associated with adult intimate relationship functioning, adjusting for childhood family and individual factors, and that these associations would be mediated by participants' current mental health. The analysis for intimate relationship quality showed that current mental health reduced the association between physical abuse and poor relationship quality (beta 0.09 (se 0.02) to 0.08 (0.02)) and between sexual abuse and this outcome to a non-significant level ((beta 0.07 (se 0.03) to 0.05 (0.03)). The analysis for adult attachment security showed that current mental health reduced the association between physical abuse and insecure attachment to a non significant level (OR 1.33 (95% CI 1.02-1.76) to OR 1.31 (0.98-1.76)) and between sexual abuse and this outcome (OR 1.89 (1.36-2.65) to OR 1.74 (1.19-2.52)). The importance of current mental health functioning in accounting for continuity in intimate relationship functioning from childhood to young adulthood is discussed. PMID- 26270934 TI - The Child PTSD Symptom Scale: An Investigation of Its Psychometric Properties. AB - The current study addresses the need for accurate measurement of posttraumatic stress disorder (PTSD) symptoms in youth by investigating the psychometric properties of the Child PTSD Symptom Scale (CPSS). The factor structure, reliability, and concurrent and discriminant validity of the CPSS were investigated in a sample of 206 6th- to 12th-grade adolescents. Exploratory and confirmatory factor analysis supported a single-factor structure, which was contrary to the hypothesized three-factor structure. Scores comprising this one factor structure were also associated with high reliability (alpha = .93), and tests of concurrent and discriminant validity were also strong. The implications of these findings are discussed, with particular emphasis on future directions for research on self-report measures for adolescent PTSD symptoms. PMID- 26270935 TI - Prehospital Care of Burn Patients and Trajectories on Survival. AB - We sought to identify factors associated with the prognosis and survival of burn patients by analyzing data related to the prehospital treatment of burn patients transferred directly to the burn unit from the accident site. We also aimed to assess the role of prehospital physicians and paramedics providing care to major burn patients. This study included adult burn patients with severe burns treated between 2006 and 2010. Prehospital patient records and clinical data collected during treatment were analyzed, and the Injury Severity Scale (ISS) was calculated. Patients were grouped into two cohorts based on the presence or absence of a physician during the prehospital phase. Data were analyzed with reference to survival by multivariable regression model. Specific inclusion criteria resulted in a sample of 67 patients. The groups were comparable with regard to age, gender, and injury etiology. Patients treated by prehospital physicians (group 1, n = 49) were more severely injured than patients treated by paramedics (group 2, n = 18) in terms of total burn surface area (%TBSA) (32% vs. 17%, p = 0.033), ISS (25 vs. 8, p < 0.000), and inhalation injuries (51% vs. 16%, p = 0.013), and presented with a higher pulse rate, lower systolic blood pressure, and lower median pH. Age, gender, %TBSA, and ISS were significantly associated with survival in both groups. Survival at 30 days was associated with age, gender, the amount of intravenous fluids (in liters) received during the first 24 hours, and the final %TBSA. Variables found to be independently associated by multivariable regression model with 30 day mortality were age, female gender, and final TBSA. We identified prehospital prognostic factors affecting patient outcomes. Based on the results from this study, our current EMS system is capable of identifying seriously injured burn patients who may benefit from physician attendance at the injury scene. PMID- 26270936 TI - Seasonal foraging patterns of forest-grazing Japanese Black heifers with increased plasma total antioxidant capacity. AB - Forest-grazing enables the intake of high total antioxidant capacity (TAC) plants that might be beneficial for the TAC status of cattle. This study evaluated the relation between the seasonal foraging patterns of forest-grazing Japanese Black (JB) heifers or the TAC levels in shrubs and trees and the changes of plasma TAC. We examined 12 JB heifers, four each of which were allocated to forest-grazing (F), pasture-grazing, and pen-housed groups. The plasma TAC level in F heifers on July 26, August 13, 30 and September 17 were significantly higher than those on April 27 and June 4 (P < 0.05). In F group, the mean rates of foraging frequency (FF) of shrubs and trees during July 5-8 and September 13-16 were much higher than that during May 31-June 3 (P < 0.05). The rate of FF of grass significantly decreased later in the season (P < 0.05). The mean TAC levels in these shrubs and trees were higher than those in grasses, concentrates, and timothy hay. Results suggest that an important factor in the increase of plasma TAC in forest-grazing cattle might be the increased foraging of TAC-rich shrubs and trees during summer fall. PMID- 26270937 TI - Correction: Evaluation of Limiting Climatic Factors and Simulation of a Climatically Suitable Habitat for Chinese Sea Buckthorn. PMID- 26270939 TI - Up-regulation of Cathepsin G in the Development of Chronic Postsurgical Pain: An Experimental and Clinical Genetic Study. AB - BACKGROUND: Proteases have been shown to modulate pain signaling in the spinal cord and may contribute to the development of chronic postsurgical pain. By using peripheral inflammation in rats as a chronic pain model, the authors identified the deregulation of proteases and their inhibitors as a hallmark of chronic pain development using a genome-wide screening approach. METHODS: A microarray analysis was performed and identified spinal cathepsin G (CTSG) as the most up regulated gene in rats with persistent hyperalgesia after intraplantar injection of complete Freund's adjuvant (n = 4). Further experiments were performed to elucidate the mechanisms of CTSG-induced hyperalgesia by intrathecally applying specific CTSG inhibitor (n = 10). The authors also evaluated the association between CTSG gene polymorphisms and the risk of chronic postsurgical pain in 1,152 surgical patients. RESULTS: CTSG blockade reduced heat hyperalgesia, accompanied by a reduction in neutrophil infiltration and interleukin 1beta levels in the dorsal horns. In the gene association study, 246 patients (21.4%) reported chronic postsurgical pain at 12-month follow-up. Patients with AA genotypes at polymorphisms rs2070697 (AA-15.3%, GA-24.1%, and GG-22.3%) or rs2236742 (AA-6.4%, GA-20.4%, and GG-22.6%) in the CTSG gene had lower risk for chronic postsurgical pain compared with wild-types. The adjusted odds ratios were 0.67 (95% CI, 0.26 to 0.99) and 0.34 (95% CI, 0.21 to 0.98), respectively. CONCLUSIONS: This study demonstrated that CTSG is a pronociceptive mediator in both animal model and human study. CTSG represents a new target for pain control and a potential marker to predict patients who are prone to develop chronic pain after surgery. PMID- 26270938 TI - Risk of a Diagnosis of Dementia for Elderly Medicare Beneficiaries after Intensive Care. AB - BACKGROUND: Critical illness is likely associated with an increased risk of dementia, but the magnitude remains uncertain. METHODS: The cohort was a random 2.5% sample of Medicare beneficiaries who received intensive care in 2005 and survived to hospital discharge. Patients were matched with general population controls (age, sex, and race) with 3 yr of follow-up. The authors used an extended Cox model to assess the risk of a diagnosis of dementia, adjusting for the known risk factors for dementia, and the competing risk of death. RESULTS: Among 10,348 intensive care patients who survived to hospital discharge, dementia was newly diagnosed in 1,648 (15.0%) over the 3 yr of follow-up versus 12.2% in controls (incidence per 1,000 person-years, 73.6; 95% CI, 70.0 to 77.1 vs. 45.8; 95% CI, 43.2 to 48.3; hazard ratio [HR], 1.61; 95% CI, 1.50 to 1.74; P < 0.001). After accounting for the known risk factors in the year before the index hospitalization, the risk of receiving a diagnosis of dementia remained increased in patients who received intensive care (adjusted HR, 1.43; 95% CI, 1.32 to 1.54; P < 0.001). Inclusion of identifiable risk factors accrued during the quarter of critical illness accounted for almost all of the increased risks (adjusted HR, 1.09; 95% CI, 1.00 to 1.20; P = 0.06). CONCLUSIONS: Elderly critical care survivors have a 60% increased relative risk, but only 3% increased absolute risk, of receiving a diagnosis of dementia in the subsequent 3 yr compared with the general population. This increased risk is not accounted for by risk factors preexisting the critical illness. Surveillance bias, which increases the likelihood of receiving a diagnosis of dementia, could account for some or all of these additional risks. PMID- 26270941 TI - Shifting to Translational Research on Postoperative Pain and Its Chronification. PMID- 26270940 TI - Astrocytes Protect against Isoflurane Neurotoxicity by Buffering pro-brain derived Neurotrophic Factor. AB - BACKGROUND: Isoflurane induces cell death in neurons undergoing synaptogenesis via increased production of pro-brain-derived neurotrophic factor (proBDNF) and activation of postsynaptic p75 neurotrophin receptor (p75). Astrocytes express p75, but their role in neuronal p75-mediated cell death remains unclear. The authors investigated whether astrocytes have the capacity to buffer increases in proBDNF and protect against isoflurane/p75 neurotoxicity. METHODS: Cell death was assessed in day in vitro (DIV) 7 mouse primary neuronal cultures alone or in co culture with age-matched or DIV 21 astrocytes with propidium iodide 24 h after 1 h exposure to 2% isoflurane or recombinant proBDNF. Astrocyte-targeted knockdown of p75 in co-culture was achieved with small-interfering RNA and astrocyte specific transfection reagent and verified with immunofluorescence microscopy. proBDNF levels were assessed by enzyme-linked immunosorbent assay. Each experiment used six to eight replicate cultures/condition and was repeated at least three times. RESULTS: Exposure to isoflurane significantly (P < 0.05) increased neuronal cell death in primary neuronal cultures (1.5 +/- 0.7 fold, mean +/- SD) but not in co-culture with DIV 7 (1.0 +/- 0.5 fold) or DIV 21 astrocytes (1.2 +/- 1.2 fold). Exogenous proBDNF dose dependently induced neuronal cell death in both primary neuronal and co-cultures, an effect enhanced by astrocyte p75 inhibition. Astrocyte-targeted p75 knockdown in co-cultures increased media proBDNF (1.2 +/- 0.1 fold) and augmented isoflurane-induced neuronal cell death (3.8 +/- 3.1 fold). CONCLUSIONS: The presence of astrocytes provides protection to growing neurons by buffering increased levels of proBDNF induced by isoflurane. These findings may hold clinical significance for the neonatal and injured brain where increased levels of proBDNF impair neurogenesis. PMID- 26270942 TI - What's changed in the management of the frozen shoulder? AB - Frozen shoulder is a painful condition in which movement of the shoulder becomes restricted. It can interfere with domestic and social activities and affect the ability to work. The condition can vary from mild to severe in terms of pain and/or restricted movement. We last reviewed the management of frozen shoulder 15 years ago. We concluded then that there was no clear evidence that any treatment could shorten the natural history of the condition and found little evidence as to the best management option. Here, we review the evidence on treatment approaches published in the meantime. PMID- 26270943 TI - Structure-Based Virtual Screening and Biological Evaluation of a Calpain Inhibitor for Prevention of Selenite-Induced Cataractogenesis in an in Vitro System. AB - Calpains belong to the family of calcium-dependent, structurally related intracellular cysteine proteases that exhibit significant functions in evolution of different types of cataracts in human as well as animal models. Application of calpain inhibitors generated through a virtual screening workflow may provide new avenues for the prevention of cataractogenesis. Hence, in the current study, compounds were first screened for potent calpain inhibitory activity by employing a structure-based approach, and the screening results were then validated through biological experiments in rat lenses. A hit compound, HTS08688, was obtained by structure-based virtual screening. A micromolar concentration of HTS08688 was found to prevent in vitro cataractogenesis in isolated Wistar rat lenses, while maintaining the antioxidant and calcium concentrations at near normal levels. Inhibition of superoxide anion generation, as observed through cytochemical localization studies, and maintenance of structural integrity, as demonstrated by histological analysis of lenticular tissue, also suggested that HTS08688 can ameliorate the cataractous condition induced by selenite in an in vitro rodent model. A cell proliferation assay was performed; the IC 50 value of the screened calpain inhibitor, HTS08688, against human lenticular epithelial cells-b3 was found to be 177 MUM/mL. This combined theoretical and experimental approach has demonstrated a potent lead compound, HTS08688, that exhibits putative anticataractogenic activity by virtue of its potential to inhibit calpain. PMID- 26270944 TI - Prescription contraception use: a cross-sectional population study of psychosocial determinants. AB - OBJECTIVE: Many forms of contraception are available on prescription only for example, the oral contraceptive pill (OCP) and long-acting reversible contraceptives (LARCs). In this analysis we aim to identify key determinants of prescription contraceptive use. DESIGN: Cross-sectional population survey. Data on sociodemographic indices, concerns about the OCP and perceived barriers to access were collected. SETTING: Data set constructed from a representative population-based telephone survey of community dwelling adults in the Republic of Ireland (RoI) PARTICIPANTS: 1515 women aged between 18 and 45 years MAIN OUTCOME MEASURE: Self-reported user of the OCP or LARCs (intrauterine contraception, contraceptive injections or subdermal contraceptive implants) in the previous 12 months. RESULTS: For at least some of the previous year, 35% had used the OCP and 14% had used LARCs, while 3% had used two or more of these methods. OCP users were significantly younger, more likely to be unmarried and had higher income than non-users. Overall, 68% agreed with the statement 'that taking a break from long-term use of the contraceptive pill is a good idea' and 37% agreed with the statement that 'the OCP has dangerous side effects' and this was the strongest predictor variable of non-use of the OCP. Intrauterine contraception users were significantly older, more likely to be married and had lower income than non users. Injections or subdermal contraceptive implant users were significantly younger, less likely to be married, had lower income and were less likely to agree that taking a break from long-term use of the pill is a good idea than non users. CONCLUSIONS: Prescription contraceptive use is sociodemographically patterned, with LARCs in particular being associated with lower incomes in the RoI. Concerns about the safety of the OCP remain prevalent and are important and modifiable determinants of contraceptive-related behaviour. PMID- 26270945 TI - Effective components of exercise and physical activity-related behaviour-change interventions for chronic non-communicable diseases in Africa: protocol for a systematic mixed studies review with meta-analysis. AB - INTRODUCTION: Chronic non-communicable diseases (NCDs) account for a high burden of mortality and morbidity in Africa. Evidence-based clinical guidelines recommend exercise training and promotion of physical activity behaviour changes to control NCDs. Developing such interventions in Africa requires an understanding of the essential components that make them effective in this context. This is a protocol for a systematic mixed studies review that aims to determine the effective components of exercise and physical activity-related behaviour-change interventions for chronic diseases in Africa, by combining quantitative and qualitative research evidence from studies published until July 2015. METHODS AND ANALYSIS: We will conduct a detailed search to identify all published and unpublished studies that assessed the effects of exercise and physical activity-related interventions or the experiences/perspectives of patients to these interventions for NCDs from bibliographic databases and the grey literature. Bibliographic databases include MEDLINE, EMBASE, CENTRAL (Cochrane Central Register of Controlled Trials), PsycINFO, CINAHL and Web of Science. We will include the following African regional databases: African Index Medicus (AIM) and AFROLIB, which is the WHO's regional office database for Africa. The databases will be searched from inception until 18 July 2015. Appraisal of study quality will be performed after results synthesis. Data synthesis will be performed independently for quantitative and qualitative data using a mixed methods sequential explanatory synthesis for systematic mixed studies reviews. Meta-analysis will be conducted for the quantitative studies, and thematic synthesis for qualitative studies and qualitative results from the non-controlled observational studies. The primary outcome will include exercise adherence and physical activity behaviour changes. This review protocol is reported according to Preferred Reporting Items for Systematic reviews and Meta Analysis protocols (PRISMA-P) 2015 guidelines. ETHICS AND DISSEMINATION: There is no ethical requirement for this study, as it utilises published data. This review is expected to inform the development of exercise and physical activity-related behaviour-change interventions in Africa, and will be presented at conferences, and published in peer reviewed journals and a PhD thesis at King's College London. PROTOCOL REGISTRATION NUMBER: This study was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 22 January 2015 (registration number: PROSPERO 2015: CRD42015016084). PMID- 26270946 TI - After the diabetes care trial ends, now what? A 1-year follow-up of the RxING study. AB - INTRODUCTION: There is strong evidence that pharmacist care improves patients' glycaemic control. However, the sustainability and durability of such interventions beyond the research period is not known. RxING was the first trial of pharmacist prescribing in diabetes and it showed an improvement in glycated haemoglobin (HbA1c) of 1.8% over 6 months. OBJECTIVE: 1 degrees objective: To evaluate glycaemic control in the RxING study patients 12 months after the end of the formal study follow-up. 2 degrees objective: To assess the patients' risk of cardiovascular events in the next 10 years. METHODS: We contacted the participating pharmacists to check if the patients who participated in the RxING study are still taking insulin, the dose of insulin they are taking, and their HbA1c. There were no mandated follow-up visits with the pharmacist after the study completion. RESULTS: A total of 100 patients with poorly controlled type 2 diabetes were enrolled in the original RxING study; 93 of them completed the study, while 83 participated in the 12-month follow-up. Seventy-five patients were still taking insulin, with the average dose increasing from 31.1 units (SD 18.4) at study completion to 37.4 units (SD 30.8) (95% CI -13.3 to 0.88, p=0.085). HbA1c was reduced from 9.1% (SD 1) at baseline to 7.3% (SD 0.9) at study completion (95% CI 1.4 to 2, p <0.001), and increased to 8.1% (SD 1.3) 12 months later (95% CI -1.1 to -0.5, p <0.001 vs study completion). CONCLUSIONS: Twelve months after completing the intervention, approximately half of the glycaemic control gains were lost. This highlights the importance of structured follow-up with the pharmacist in this patient population. TRIAL REGISTRATION NUMBER: clinicaltrials.gov; Identifier: NCT01335763. PMID- 26270947 TI - Workplace health and safety issues among community nurses: a study regarding the impact on providing care to rural consumers. AB - OBJECTIVES: The objective of the study was to investigate the types of workplace health and safety issues rural community nurses encounter and the impact these issues have on providing care to rural consumers. METHODS: The study undertook a narrative inquiry underpinned by a phenomenological approach. Community nursing staff who worked exclusively in rural areas and employed in a permanent capacity were contacted among 13 of the 16 consenting healthcare services. All community nurses who expressed a desire to participate were interviewed. Data were collected using semistructured interviews with 15 community nurses in rural and remote communities. Thematic analysis was used to analyse interview data. RESULTS: The role, function and structures of community nursing services varied greatly from site to site and were developed and centred on meeting the needs of individual communities. In addition, a number of workplace health and safety challenges were identified and were centred on the geographical, physical and organisational environment that community nurses work across. The workplace health and safety challenges within these environments included driving large distances between client's homes and their office which lead to working in isolation for long periods and without adequate communication. In addition, other issues included encountering, managing and developing strategies to deal with poor client and carer behaviour; working within and negotiating working environments such as the poor condition of patient homes and clients smoking; navigating animals in the workplace; vertical and horizontal violence; and issues around workload, burnout and work-related stress. CONCLUSIONS: Many nurses achieved good outcomes to meet the needs of rural community health consumers. Managers were vital to ensure that service objectives were met. Despite the positive outcomes, many processes were considered unsafe by community nurses. It was identified that greater training and capacity building are required to meet the needs among all staff. PMID- 26270948 TI - Antiepileptic drugs and the risk of ischaemic stroke and myocardial infarction: a population-based cohort study. AB - OBJECTIVES: Hepatic enzyme-inducing antiepileptic drugs (AEDs) increase serum lipid levels and other atherogenic markers via the induction of cytochrome P450 and may therefore increase the risk of vascular events. We sought to assess the risk of ischaemic stroke and myocardial infarction (MI) according to AED enzymatic properties. DESIGN: Population-based cohort study with nested case control analysis. SETTING: 650 general practices in the UK contributing to the Clinical Practice Research Datalink. PARTICIPANTS: A cohort of 252,407 incident AED users aged 18 or older between January 1990 and April 2013. For each case of ischaemic stroke or MI, up to 10 controls were randomly selected among the cohort members in the risk sets defined by the case and matched on age, sex, indication for AED, calendar time and duration of follow-up. INTERVENTIONS: Current use of enzyme-inducing and enzyme-inhibiting AEDs compared with non-inducing AEDs. PRIMARY OUTCOME MEASURES: Incidence rate ratios (RRs) of ischaemic stroke and MI. RESULTS: 5069 strokes and 3636 MIs were identified during follow-up. Inducing AEDs use was associated with a small increased risk of ischaemic stroke (RR=1.16, 95% CI 1.02 to 1.33) relative to non-inducing AEDs, most likely due to residual confounding. However, current use of inducing AEDs for >= 24 months was associated with a 46% increased risk of MI (RR=1.46, 95% CI 1.15 to 1.85) compared with the same duration of non-inducing AED, corresponding to a risk difference of 1.39/1000 (95% CI 0.33 to 2.45) persons per year. Current use of inhibiting AED was associated with a decreased risk of MI (RR=0.81, 95% CI 0.66 to 1.00). CONCLUSIONS: The use of enzyme-inducing AEDs was not associated with an increased risk of ischaemic stroke; a small increase of MI with prolonged use was observed. In contrast, use of inhibiting AEDs was associated with a decreased risk of MI. PMID- 26270950 TI - Unintentional fall-related mortality in the elderly: comparing patterns in two countries with different demographic structure. AB - OBJECTIVES: Falls are among the major external causes of unintentional injury and injury-related mortality in the elderly. The aim of this study was to compare the patterns of unintentional fall-related mortalities in two countries with different demographic structure: Slovakia and Austria in 2003-2010. METHODS: A study was conducted using death certificate data, trends of fall-related mortality in the elderly (over 65 years) in Austria and Slovakia were compared. Crude and age-standardised mortality rates were calculated. Rate ratios were used to quantify differences based on age, sex and country. The role of demographic structure and population ageing was considered. RESULTS: The annual average crude mortality for Slovakia was 28.82, for Austria 54.19 per 100,000 person-years. Increasing rates were observed towards higher age in both countries. Males had higher mortality than females (1.18 times higher in Austria, 2.4 higher in Slovakia). In ages over 75 years rates were significantly higher in Austria, compared to Slovakia. Injuries to head (in males) and hip (in females) were most commonly the underlying cause of death. The proportion of populations over 65 and over 80 and rate of their increase were higher in Austria than in Slovakia. CONCLUSIONS: We conclude that higher proportions of the elderly population of Austria could have contributed to the higher fall-related mortality rates compared to Slovakia, especially in females over 80 years. Our study quantified the differences between two countries with different structure of the elderly population and these findings could be used in planning future needs of health and social services and to plan prevention in countries where a rapid increase in age of the population can be foreseen. PMID- 26270949 TI - Systemic exposure to menthol following administration of peppermint oil to paediatric patients. AB - OBJECTIVE: Peppermint oil (PMO) has been used to treat abdominal ailments dating to ancient Egypt, Greece and Rome. Despite its increasing paediatric use, as in irritable bowel syndrome (IBS) treatment, the pharmacokinetics (PK) of menthol in children given PMO has not been explored. DESIGN AND SETTING: Single-site, exploratory pilot study of menthol PK following a single 187 mg dose of PMO. Subjects with paediatric Rome II defined (IBS; n=6, male and female, 7-15 years of age) were enrolled. Blood samples were obtained before PMO administration and at 10 discrete time points over a 12 h postdose period. Menthol was quantitated from plasma using a validated gas chromatography mass spectrometry technique. Menthol PK parameters were determined using a standard non-compartmental approach. RESULTS: Following a dose of PMO, a substantial lag time (range 1-4 h) was seen in all subjects for the appearance of menthol which in turn, produced a delayed time of peak (Tmax=5.3 +/- 2.4 h) plasma concentration (Cmax=698.2 +/- 245.4 ng/mL). Tmax and Tlag were significantly more variable than the two exposure parameters; Cmax, mean residence time and total area under the curve (AUC=4039.7 +/- 583.8 ng/mL * h) which had a coefficient of variation of <20%. CONCLUSIONS: Delayed appearance of menthol in plasma after oral PMO administration in children is likely a formulation-specific event which, in IBS, could increase intestinal residence time of the active ingredient. Our data also demonstrate the feasibility of using menthol PK in children with IBS to support definitive studies of PMO dose-effect relationships. PMID- 26270951 TI - Long-term non-invasive ventilation therapies in children: a scoping review protocol. AB - INTRODUCTION: Non-invasive ventilation (NIV) in children has become an increasingly common modality of breathing support where pressure support is delivered through a mask interface or less commonly through other non-invasive interfaces. At this time, NIV is considered a first-line option for ventilatory support of chronic respiratory insufficiency associated with a range of respiratory and sleep disorders. Previous reviews on the effectiveness, complications and adherence to NIV treatment have lacked systematic methods. The purpose of this scoping review is to provide an overview of the evidence for the use of long-term NIV in children. METHODS AND ANALYSIS: We will use previously established scoping methodology. Ten electronic databases will be searched to identify studies in children using NIV for longer than 3 months outside an intensive care setting. Grey literature search will include conference proceedings, thesis and dissertations, unpublished trials, reports from regulatory agencies and manufacturers. Two reviewers will independently screen titles and abstracts for inclusion, followed by full-text screening of potentially relevant articles to determine final inclusion. Data synthesis will be performed at three levels: (1) an analysis of the number, publication type, publication year, and country of publication of the studies; (2) a summary of the study designs, outcomes measures used; (3) a thematic analysis of included studies by subgroups. ETHICS AND DISSEMINATION: This study will provide a wide and rigorous overview of the evidence on the use of long-term NIV in children and provide critical information for healthcare professionals and policymakers to better care for this group of children. We will disseminate our findings through conference proceedings and publications, and evaluate the results for further systematic reviews and meta-analyses. PMID- 26270953 TI - Effect of an interactive therapeutic robotic animal on engagement, mood states, agitation and psychotropic drug use in people with dementia: a cluster-randomised controlled trial protocol. AB - INTRODUCTION: Apathy, agitated behaviours, loneliness and depression are common consequences of dementia. This trial aims to evaluate the effect of a robotic animal on behavioural and psychological symptoms of dementia in people with dementia living in long-term aged care. METHODS AND ANALYSIS: A cluster randomised controlled trial with three treatment groups: PARO (robotic animal), Plush-Toy (non-robotic PARO) or Usual Care (Control). The nursing home sites are Australian Government approved and accredited facilities of 60 or more beds. The sites are located in South-East Queensland, Australia. A sample of 380 adults with a diagnosis of dementia, aged 60 years or older living in one of the participating facilities will be recruited. The intervention consists of three individual 15 min non-facilitated sessions with PARO or Plush-Toy per week, for a period of 10 weeks. The primary outcomes of interest are improvement in agitation, mood states and engagement. Secondary outcomes include sleep duration, step count, change in psychotropic medication use, change in treatment costs, and staff and family perceptions of PARO or Plush-Toy. Video data will be analysed using Noldus XT Pocket Observer; descriptive statistics will be used for participants' demographics and outcome measures; cluster and individual level analyses to test all hypotheses and Generalised Linear Models for cluster level and Generalised Estimation Equations and/or Multi-level Modeling for individual level data. ETHICS AND DISSEMINATION: The study participants or their proxy will provide written informed consent. The Griffith University Human Research Ethics Committee has approved the study (NRS/03/14/HREC). The results of the study will provide evidence of the efficacy of a robotic animal as a psychosocial treatment for the behavioural and psychological symptoms of dementia. Findings will be presented at local and international conference meetings and published in peer reviewed journals. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trials Registry number ACTRN12614000508673 date registered 13/05/2014. PMID- 26270952 TI - Should HFE p.C282Y homozygotes with moderately elevated serum ferritin be treated? A randomised controlled trial comparing iron reduction with sham treatment (Mi-iron). AB - INTRODUCTION: HFE p.C282Y homozygosity is the most common cause of hereditary haemochromatosis. There is currently insufficient evidence to assess whether non specific symptoms or hepatic injury in homozygotes with moderately elevated iron defined as a serum ferritin (SF) of 300-1000 ug/L are related to iron overload. As such the evidence for intervention in this group is lacking. We present here methods for a study that aims to evaluate whether non-specific symptoms and hepatic fibrosis markers improve with short-term normalisation of SF in p.C282Y homozygotes with moderate elevation of SF. METHODS AND ANALYSIS: Mi-iron is a prospective, multicentre, randomised patient-blinded trial conducted in three centres in Victoria and Queensland, Australia. Participants who are HFE p.C282Y homozygotes with SF levels between 300 and 1000 MUg/L are recruited and randomised to either the treatment group or to the sham treatment group. Those in the treatment group have normalisation of SF by 3-weekly erythrocytapheresis while those in the sham treatment group have 3-weekly plasmapheresis and thus do not have normalisation of SF. Patients are blinded to all procedures. All outcome measures are administered prior to and following the course of treatment/sham treatment. Patient reported outcome measures are the Modified Fatigue Impact Scale (MFIS-primary outcome), Hospital Anxiety and Depression Scale (HADS), Medical Outcomes Study 36-item short form V.2 (SF36v2) and Arthritis Impact Measurement Scale 2 short form (AIMS2-SF). Liver injury and hepatic fibrosis are assessed with transient elastography (TE), Fibrometer and Hepascore, while oxidative stress is assessed by measurement of urine and serum F2-isoprostanes. ETHICS AND DISSEMINATION: This study has been approved by the Human Research Ethics Committees of Austin Health, Royal Melbourne Hospital and Royal Brisbane and Women's Hospital. Study findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION: Trial identifier: NCT01631708; Registry: ClinicalTrials.gov. PMID- 26270954 TI - Synthesis and Characterization of 5-Hydroxy-2-(2-phenylethyl)chromone (5-HPEC) and Its Analogues as Non-nitrogenous 5-HT2B Ligands. AB - The involvement of the neurotransmitter serotonin (5-HT) in numerous physiological functions is often attributed to the diversity of receptors with which it interacts. Ligands targeting serotonin receptor 2B (5-HT2B) have received renewed interest for their potential to help understand the role of 5 HT2B in migraines, drug abuse, neurodegenerative diseases, and irritable bowel syndrome. To date, most of the ligands targeting 5-HT2B have been nitrogen containing compounds. The natural product 5-hydroxy-2-(2-phenylethyl)chromone (5 HPEC, 5) has been shown previously to act as a non-nitrogenous antagonist for the 5-HT2B receptor (pKi = 5.6). This report describes further progress on the study of the structure-activity relationship of both naturally occurring and synthetic compounds bearing the 2-(2-phenylethyl)chromone scaffold at the 5-HT2B receptor. The inhibitory activity of the newly synthesized compounds (at 10 MUM) was tested against each of the 5-HT2 receptors. Following this assay, the binding affinity and antagonism of the most promising compounds were then evaluated at 5-HT2B. Among all the analogues, 5-hydroxy-2-(2-phenylpropyl)chromone (5-HPPC, 22h) emerged as a new lead compound, showing a 10-fold improvement in affinity (pKi = 6.6) over 5-HPEC with reasonable antagonist properties at 5-HT2B. Additionally, ligand docking studies have identified a putative binding pocket for 5-HPPC and have helped understand its improved affinity. PMID- 26270955 TI - Therapeutic Yoga: Symptom Management for Multiple Sclerosis. AB - Multiple sclerosis (MS) is the most common autoimmune inflammatory demyelinating disease of the central nervous system, affecting over 2.3 million people worldwide. According to the National Institute of Neurological Disorders and Stroke, the age of disease onset is typically between 20 and 40 years, with a higher incidence in women. Individuals with MS experience a wide range of symptoms, including declining physical, emotional, and psychological symptoms (e.g., fatigue, imbalance, spasticity, chronic pain, cognitive impairment, bladder and bowel dysfunction, visual and speech impairments, depression, sensory disturbance, and mobility impairment). To date, both the cause of and cure for MS remain unknown. In recent years, more individuals with MS have been pursuing alternative methods of treatment to manage symptoms of the disease, including mind-body therapies such as yoga, meditation, breathing, and relaxation techniques. It has been suggested that the practice of yoga may be a safe and effective way of managing symptoms of MS. Therefore, the purpose of this paper is to summarize the most relevant literature on exercise and mind-body modalities to treat MS symptoms and, more specifically, the benefits and potential role of yoga as an alternative treatment of symptom management for individuals with MS. The article also discusses future directions for research. PMID- 26270956 TI - CO2 Fixation, Lipid Production, and Power Generation by a Novel Air-Lift-Type Microbial Carbon Capture Cell System. AB - An air-lift-type microbial carbon capture cell (ALMCC) was constructed for the first time by using an air-lift-type photobioreactor as the cathode chamber. The performance of ALMCC in fixing high concentration of CO2, producing energy (power and biodiesel), and removing COD together with nutrients was investigated and compared with the traditional microbial carbon capture cell (MCC) and air-lift type photobioreactor (ALP). The ALMCC system produced a maximum power density of 972.5 mW.m(-3) and removed 86.69% of COD, 70.52% of ammonium nitrogen, and 69.24% of phosphorus, which indicate that ALMCC performed better than MCC in terms of power generation and wastewater treatment efficiency. Besides, ALMCC demonstrated 9.98- and 1.88-fold increases over ALP and MCC in the CO2 fixation rate, respectively. Similarly, the ALMCC significantly presented a higher lipid productivity compared to those control reactors. More importantly, the preliminary analysis of energy balance suggested that the net energy of the ALMCC system was significantly superior to other systems and could theoretically produce enough energy to cover its consumption. In this work, the established ALMCC system simultaneously achieved the high level of CO2 fixation, energy recycle, and municipal wastewater treatment effectively and efficiently. PMID- 26270957 TI - Pediatric combined liver-kidney transplantation: a 2015 update. AB - PURPOSE OF REVIEW: The experience of combined liver-kidney transplantation (CLKT) is limited in pediatric populations. This strategy is, however, required in specific diseases such as metabolic diseases (namely primary hyperoxaluria type one and methylmalonic acidemia), autosomal recessive polycystic kidney disease, miscellaneous ciliopathies and atypical hemolytic uremic syndrome. RECENT FINDINGS: Different series and registry studies have confirmed the feasibility of pediatric CLKT with encouraging results in the long term, even in the youngest and smallest patients, provided that highly trained multidisciplinary teams are involved in this global management. As such, the long-term outcomes after CLKT are currently comparable to that of isolated liver or kidney transplantations, even though the immediate postoperative period remains challenging. SUMMARY: Some questions remain nevertheless unanswered, such as the respective place of combined versus sequential liver-kidney transplantation, especially in primary hyperoxaluria and autosomal recessive polycystic kidney disease. The aim of this review was therefore to provide a 2015 update on pediatric CLKT. In the future, international collaborative studies and registries may help to improve our knowledge of this rare and still highly challenging technique. PMID- 26270958 TI - An integrated system for identifying the hidden assassins in traditional medicines containing aristolochic acids. AB - Traditional herbal medicines adulterated and contaminated with plant materials from the Aristolochiaceae family, which contain aristolochic acids (AAs), cause aristolochic acid nephropathy. Approximately 256 traditional Chinese patent medicines, containing Aristolochiaceous materials, are still being sold in Chinese markets today. In order to protect consumers from health risks due to AAs, the hidden assassins, efficient methods to differentiate Aristolochiaceous herbs from their putative substitutes need to be established. In this study, 158 Aristolochiaceous samples representing 46 species and four genera as well as 131 non-Aristolochiaceous samples representing 33 species, 20 genera and 12 families were analyzed using DNA barcodes based on the ITS2 and psbA-trnH sequences. Aristolochiaceous materials and their non-Aristolochiaceous substitutes were successfully identified using BLAST1, the nearest distance method and the neighbor-joining (NJ) tree. In addition, based on sequence information of ITS2, we developed a Real-Time PCR assay which successfully identified herbal material from the Aristolochiaceae family. Using Ultra High Performance Liquid Chromatography-Mass Spectrometer (UHPLC-HR-MS), we demonstrated that most representatives from the Aristolochiaceae family contain toxic AAs. Therefore, integrated DNA barcodes, Real-Time PCR assays using TaqMan probes and UHPLC-HR-MS system provides an efficient and reliable authentication system to protect consumers from health risks due to the hidden assassins (AAs). PMID- 26270959 TI - Paraformaldehyde Fixation May Lead to Misinterpretation of the Subcellular Localization of Plant High Mobility Group Box Proteins. AB - Arabidopsis High Mobility Group Box (HMBG) proteins were previously found associated with the interphase chromatin but not the metaphase chromosome. However, these studies are usually based on immunolocalization analysis involving paraformaldehyde fixation. Paraformaldehyde fixation has been widely adapted to preserved cell morphology before immunofluorescence staining. On one hand, the processed cells are no longer living. On the other hand, the processing may lead to misinterpretation of localization. HMGBs from Arabidopsis were fused with enhanced green fluorescence protein (EGFP) and transformed into tobacco BY-2 cells. Basically, the localization of these HMGB proteins detected with EGFP fluorescence in interphase agreed with previous publications. Upon 4% paraformaldehyde fixation, AtHMGB1 was found associated with interphase but not the metaphase chromosomes as previously reported. However, when EGFP fluorescence signal was directly observed under confocal microscope without fixation, association of AtHMGB1 with metaphase chromosomes can be detected. Paraformaldehyde fixation led to dissociation of EGFP tagged AtHMBG1 protein from metaphase chromosomes. This kind of pre-processing of live specimen may lead to dissociation of protein-protein or protein-nucleic acid interaction. Therefore, using of EGFP fusion proteins in live specimen is a better way to determine the correct localization and interaction of proteins. PMID- 26270960 TI - Simple Experimental Methods for Determining the Apparent Focal Shift in a Microscope System. AB - Three-dimensional optical microscopy is often complicated by a refractive index mismatch between the sample and objective lens. This mismatch causes focal shift, a difference between sample motion and focal-plane motion, that hinders the accuracy of 3D reconstructions. We present two methods for measuring focal shift using fluorescent beads of different sizes and ring-stained fluorescent beads. These simple methods are applicable to most situations, including total internal reflection objectives and samples very close to the interface. For distances 0 1.5 MUm into an aqueous environment, our 1.49-NA objective has a relative focal shift of 0.57 +/- 0.02, significantly smaller than the simple n2/n1 approximation of 0.88. We also expand on a previous sub-critical angle theory by means of a simple polynomial extrapolation. We test the validity of this extrapolation by measuring the apparent focal shift in samples where the refractive index is between 1.33 and 1.45 and with objectives with numerical apertures between 1.25 and 1.49. PMID- 26270961 TI - Influence of the Lower Jaw Position on the Running Pattern. AB - INTRODUCTION: The effects of manipulated dental occlusion on body posture has been investigated quite often and discussed controversially in the literature. Far less attention has been paid to the influence of dental occlusion position on human movement. If human movement was analysed, it was mostly while walking and not while running. This study was therefore designed to identify the effect of lower jaw positions on running behaviour according to different dental occlusion positions. METHODS: Twenty healthy young recreational runners (mean age = 33.9+/ 5.8 years) participated in this study. Kinematic data were collected using an eight-camera Vicon motion capture system (VICON Motion Systems, Oxford, UK). Subjects were consecutively prepared with four different dental occlusion conditions in random order and performed five running trials per test condition on a level walkway with their preferred running shoes. Vector based pattern recognition methods, in particular cluster analysis and support vector machines (SVM) were used for movement pattern identification. RESULTS: Subjects exhibited unique movement patterns leading to 18 clusters for the 20 subjects. No overall classification of the splint condition could be observed. Within individual subjects different running patterns could be identified for the four splint conditions. The splint conditions lead to a more symmetrical running pattern than the control condition. DISCUSSION: The influence of an occlusal splint on running pattern can be confirmed in this study. Wearing a splint increases the symmetry of the running pattern. A more symmetrical running pattern might help to reduce the risk of injuries or help in performance. The change of the movement pattern between the neutral condition and any of the three splint conditions was significant within subjects but not across subjects. Therefore the dental splint has a measureable influence on the running pattern of subjects, however subjects individuality has to be considered when choosing the optimal splint condition for a specific subject. PMID- 26270962 TI - Xenopus Pkdcc1 and Pkdcc2 Are Two New Tyrosine Kinases Involved in the Regulation of JNK Dependent Wnt/PCP Signaling Pathway. AB - Protein Kinase Domain Containing, Cytoplasmic (PKDCC) is a protein kinase which has been implicated in longitudinal bone growth through regulation of chondrocytes formation. Nevertheless, the mechanism by which this occurs remains unknown. Here, we identified two new members of the PKDCC family, Pkdcc1 and Pkdcc2 from Xenopus laevis. Interestingly, our knockdown experiments revealed that these two proteins are both involved on blastopore and neural tube closure during gastrula and neurula stages, respectively. In vertebrates, tissue polarity and cell movement observed during gastrulation and neural tube closure are controlled by Wnt/Planar Cell Polarity (PCP) molecular pathway. Our results showed that Pkdcc1 and Pkdcc2 promote the recruitment of Dvl to the plasma membrane. But surprisingly, they revealed different roles in the induction of a luciferase reporter under the control of Atf2 promoter. While Pkdcc1 induces Atf2 expression, Pkdcc2 does not, and furthermore inhibits its normal induction by Wnt11 and Wnt5a. Altogether our data show, for the first time, that members of the PKDCC family are involved in the regulation of JNK dependent Wnt/PCP signaling pathway. PMID- 26270963 TI - Characterization of Cell Wall Proteins in Saccharomyces cerevisiae Clinical Isolates Elucidates Hsp150p in Virulence. AB - The budding yeast Saccharomyces cerevisiae has recently been described as an emerging opportunistic fungal pathogen. Fungal cell wall mannoproteins have been demonstrated to be involved in adhesion to inert surfaces and might be engaged in virulence. In this study, we observed four clinical isolates of S. cerevisiae with relatively hydrophobic cell surfaces. Yeast cell wall subproteome was evaluated quantitatively by liquid chromatography/tandem mass spectrometry. We identified totally 25 cell wall proteins (CWPs) from log-phase cells, within which 15 CWPs were quantified. The abundance of Scw10p, Pst1p, and Hsp150p/Pir2p were at least 2 folds higher in the clinical isolates than in S288c lab strain. Hsp150p is one of the members in Pir family conserved in pathogenic fungi Candida glabrata and Candida albicans. Overexpression of Hsp150p in lab strain increased cell wall integrity and potentially enhanced the virulence of yeast. Altogether, these results demonstrated that quantitative cell wall subproteome was analyzed in clinical isolates of S. cerevisiae, and several CWPs, especially Hsp150p, were found to be expressed at higher levels which presumably contribute to strain virulence and fungal pathogenicity. PMID- 26270964 TI - Recent Invasion of the Symbiont-Bearing Foraminifera Pararotalia into the Eastern Mediterranean Facilitated by the Ongoing Warming Trend. AB - The eastern Mediterranean is a hotspot of biological invasions. Numerous species of Indo-pacific origin have colonized the Mediterranean in recent times, including tropical symbiont-bearing foraminifera. Among these is the species Pararotalia calcariformata. Unlike other invasive foraminifera, this species was discovered only two decades ago and is restricted to the eastern Mediterranean coast. Combining ecological, genetic and physiological observations, we attempt to explain the recent invasion of this species in the Mediterranean Sea. Using morphological and genetic data, we confirm the species attribution to P. calcariformata McCulloch 1977 and identify its symbionts as a consortium of diatom species dominated by Minutocellus polymorphus. We document photosynthetic activity of its endosymbionts using Pulse Amplitude Modulated Fluorometry and test the effects of elevated temperatures on growth rates of asexual offspring. The culturing of asexual offspring for 120 days shows a 30-day period of rapid growth followed by a period of slower growth. A subsequent 48-day temperature sensitivity experiment indicates a similar developmental pathway and high growth rate at 28 degrees C, whereas an almost complete inhibition of growth was observed at 20 degrees C and 35 degrees C. This indicates that the offspring of this species may have lower tolerance to cold temperatures than what would be expected for species native to the Mediterranean. We expand this hypothesis by applying a Species Distribution Model (SDM) based on modern occurrences in the Mediterranean using three environmental variables: irradiance, turbidity and yearly minimum temperature. The model reproduces the observed restricted distribution and indicates that the range of the species will drastically expand westwards under future global change scenarios. We conclude that P. calcariformata established a population in the Levant because of the recent warming in the region. In line with observations from other groups of organisms, our results indicate that continued warming of the eastern Mediterranean will facilitate the invasion of more tropical marine taxa into the Mediterranean, disturbing local biodiversity and ecosystem structure. PMID- 26270966 TI - Plasticity and Redundancy in Proteins Important for Toxoplasma Invasion. PMID- 26270967 TI - Magnetic Clustering Effect during the Association of Biofunctionalized Magnetic Nanoparticles with Biomarkers. AB - We report herein an investigation into dynamic magnetic clustering that occurs during immunoassays as biofunctionalized magnetic nanoparticles (BMNs) become associated with biotargets. We measure the dynamic effective relaxation time taueff(t) and use scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to investigate the C-reactive protein (CRP) as it associates with the BMN Fe3O4-antiCRP to form the magnetic cluster Fe3O4-antiCRP-CRP. The results indicate that taueff(t) increases with increasing association time. In addition, the ration Deltataueff/tau0 as a function of CRP concentration follows a characteristic logistic function, which provides a basis for estimating the quantity of biomolecules with a detection sensitivity close to 0.1 ppm. After the association, SEM and TEM images show that CRP and Fe3O4-antiCRP conjugate to form Fe3O4-antiCRP-CRP clusters hundreds of nanometers in size. The SEM and TEM images provide direct evidence of the formation of magnetic clustering. PMID- 26270968 TI - Metabolic and Ventilatory Changes During and After High-Frequency Yoga Breathing. AB - BACKGROUND Practicing high-frequency yoga breathing (HFYB) induced a hypermetabolic state in a single subject during the practice but the effect has not been studied in multiple practitioners. MATERIAL AND METHODS Healthy male volunteers (n=47, group mean age +/- S.D., 23.2 +/- 4.1 years) were recruited as an experimental group and another twenty volunteers were recruited as a control group. The experimental group practiced either HFYB (Breath rate 1.0 Hz) or breath awareness (BAW) on two separate days. The sequence was reversed for alternate participants. The control group was assessed under similar conditions while sitting at ease. The breath rate (RR), tidal volume (VT), ventilation (VE), VO2, VCO2, arterial PCO2 and energy expenditure (EE Kcal/day) were assessed for 35 minutes using an open circuit oxygen consumption analyzer. The assessment period was divided into before, during and after conditions. Repeated measures analyses of variance (ANOVA) were used to compare data recorded during and after the two practices with data recorded before. Before-After comparisons in the control group were with paired t-tests. RESULTS The most relevant significant changes were increases in VE, VO2, VCO2 and EE during HFYB, while the same variables decreased during the control period. However after HFYB there was no change in VO2 or EE, although VE decreased as it did after the control period. CONCLUSIONS HFYB induces a hypermetabolic state for the duration of the practice which returns to baseline after HFYB suggesting a possible application for HFYB in hypometabolic states. PMID- 26270965 TI - The Carboxy Terminus of the Ligand Peptide Determines the Stability of the MHC Class I Molecule H-2Kb: A Combined Molecular Dynamics and Experimental Study. AB - Major histocompatibility complex (MHC) class I molecules (proteins) bind peptides of eight to ten amino acids to present them at the cell surface to cytotoxic T cells. The class I binding groove binds the peptide via hydrogen bonds with the peptide termini and via diverse interactions with the anchor residue side chains of the peptide. To elucidate which of these interactions is most important for the thermodynamic and kinetic stability of the peptide-bound state, we have combined molecular dynamics simulations and experimental approaches in an investigation of the conformational dynamics and binding parameters of a murine class I molecule (H-2Kb) with optimal and truncated natural peptide epitopes. We show that the F pocket region dominates the conformational and thermodynamic properties of the binding groove, and that therefore the binding of the C terminus of the peptide to the F pocket region plays a crucial role in bringing about the peptide-bound state of MHC class I. PMID- 26270970 TI - Evaluation of Blue Crab, Callinectes sapidus, Megalopal Settlement and Condition during the Deepwater Horizon Oil Spill. AB - The Blue Crab, Callinectes sapidus, is a commercially, culturally, and ecologically significant species in the Gulf of Mexico (GOM), whose offshore stages were likely impacted by the Deepwater Horizon oil spill (DWH). To test for DWH effects and to better understand the planktonic ecology of this species, we monitored Callinectes spp. megalopal settlement and condition at sites within and outside of the spill extent during and one year after the DWH. We tested for DWH effects by comparing 2010 settlement against baseline data available for two sites, and by testing for differences in settlement and condition inside and outside of the spill extent. We also developed time series models to better understand natural drivers of daily settlement variation (seasonal and lunar trends, hydrodynamics, wind) during 2010 and 2011. Overall, we found that neither megalopal settlement nor body weight were significantly reduced at oiled sites, but that high unexplained variation and low statistical power made detection of even large effects unlikely. Time series models revealed remarkably consistent and relatively strong seasonal and lunar trends within sites (explaining on average 28% and 9% of variation, respectively), while wind and hydrodynamic effects were weak (1-5% variation explained) and variable among sites. This study provides insights into DWH impacts as well as the natural drivers of Callinectes spp. megalopal settlement across the northern GOM. PMID- 26270969 TI - The Inflammatory Marker YKL-40 Is Elevated in Cerebrospinal Fluid from Patients with Alzheimer's but Not Parkinson's Disease or Dementia with Lewy Bodies. AB - A major difference in the revised diagnostic criteria for Alzheimer's disease (AD) is the incorporation of biomarkers to support a clinical diagnosis and allow the identification of preclinical AD due to AD neuropathological processes. However, AD-specific fluid biomarkers which specifically distinguish clinical AD dementia from other dementia disorders are still missing. Here we aimed to evaluate the disease-specificity of increased YKL-40 levels in cerebrospinal fluid (CSF) from AD patients with mild to moderate dementia (n = 49) versus Parkinson's disease (PD) (n = 61) and dementia with Lewy bodies (DLB) patients (n = 36), and non-demented controls (n = 44). Second we aimed to investigate whether altered YKL-40 levels are associated with CSF levels of other inflammation associated molecules. When correcting for age, AD patients exhibited 21.3%, 27.7% and 38.8% higher YKL-40 levels compared to non-demented controls (p = 0.0283), DLB (p = 0.0027) and PD patients (p<0.0001). The AD-associated increase in YKL-40 was not associated with CSF P-tau, T-tau or Abeta42. No relationship between increased YKL-40 and levels of the astrocytic marker glial-fibrillary acidic protein (GFAP), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and interferon gamma-induced protein 10 (IP-10) could be identified. Our results confirm previous reports of an age-associated increased in CSF YKL-40 levels and further demonstrate increased CSF YKL-40 in AD patients versus non-demented controls and patients with DLB or PD. The increase in YKL-40 levels in the AD patients was unrelated to the established CSF AD biomarkers and the inflammatory markers GFAP, MCP-1, IP-10 and IL-8, proposing YKL-40 as a marker of yet to be identified AD-related pathological processes. PMID- 26270971 TI - (1) (1)A' <- X (1)A' Electronic Transition of Protonated Coronene at 15 K. AB - The electronic spectrum of protonated coronene in the gas phase was measured at vibrational and rotational temperatures of ~15 K in a 22-pole ion trap. The (1) (1)A' <- X (1)A' electronic transition of this larger polycyclic aromatic hydrocarbon cation has an origin band maximum at 14 383.8 +/- 0.2 cm(-1) and shows distinct vibrational structure in the (1) (1)A' state. Neither the origin nor the strongest absorptions to the blue coincide with known diffuse interstellar bands, implying that protonated coronene is not a carrier. PMID- 26270972 TI - Correction to "Pump-Probe Microscopic Imaging of Jurassic-Aged Eumelanin". PMID- 26270973 TI - Quantum Calculations in Solution for Large to Very Large Molecules: A New Linear Scaling QM/Continuum Approach. AB - We present a new implementation of continuum solvation models for semiempirical Hamiltonians that allows the description of environmental effects on very large molecular systems. In this approach based on a domain decomposition strategy of the COSMO model (ddCOSMO), the solution to the COSMO equations is no longer the computational bottleneck but becomes a negligible part of the overall computation time. In this Letter, we analyze the computational impact of COSMO on the solution of the SCF equations for large to very large molecules, using semiempirical Hamiltonians, for both the new ddCOSMO implementation and the most recent, linear scaling one, based on the fast multipole method. A further analysis is on the simulation of the UV/visible spectrum of a light-harvesting pigment-protein complex. All of the results show how the new ddCOSMO algorithm paves the way to routine computations for large molecular systems in the condensed phase. PMID- 26270974 TI - Revealing Interaction of Organic Adsorbates with Semiconductor Surfaces Using Chemically Enhanced Raman. AB - Surface enhanced Raman spectroscopy (SERS) is frequently associated with "chemical enhancement" (CE), which is an effect of the chemical coupling between reporting molecules and surfaces. While SERS technique is mainly attributed to the studies of metallic surfaces, chemical coupling must be present on semiconductor surfaces as well. Here, we examine binding of trans-1,2-two(4 pyridyl) ethylene (BPE) to various crystallographic facets of PbSe semiconductor. The calculated off-resonant Raman spectra vary significantly on different crystallographic facets of PbSe, correlating with the electronic structure of each type of semiconductor surface. We distinguish situations when the charge transfer is present and when it is not, which raises the question about what exactly should be called the "chemical enhancement". We attempt to clarify this situation by introducing the concept of the "charge-transfer" and "charge transfer-less" chemical enhancement. We also demonstrate a transition between these two regimes, which exhibits a nonlinear behavior of the vibrational coupling and a significantly stronger contribution to the Raman intensity. PMID- 26270975 TI - Submonolayer-Pt-Coated Ultrathin Au Nanowires and Their Self-Organized Nanoporous Film: SERS and Catalysis Active Substrates for Operando SERS Monitoring of Catalytic Reactions. AB - For their unique properties, core-shell bimetal nanostructures are currently of immense interest. However, their synthesis is not a trivial work, and most works have been conducted on nanoparticles. We report herein a new synthetic tactic for submonolyer-Pt coated ultrathin Au nanowires (NWs). Besides providing a strong electromagnetic field for Raman signal enhancing, the underlined Au NWs markedly enhanced the catalytic activity of Pt atoms through increasing their dispersity and altering their electronic state. The integration of excellent SERS and high catalytic activity within Au@Pt NWs enable it work as platform for catalyzed reaction study. As a proof of principle, the self-organized Au@Pt NWs thin film is employed in operando SERS monitoring of the p-nitrothiophenol reduction process. In addition to providing kinetic data for structure-activity relationship study, the azo-intermidate independent path is also directly witnessed. This synthetic tactic can be extended to other metals, thus offering a general approach to modulate the physical/chemical properties of both core and shell metals. PMID- 26270976 TI - Plasmon Resonances of Semiconductor Nanocrystals: Physical Principles and New Opportunities. AB - The discovery of localized surface plasmon resonances (LSPRs) in doped semiconductor nanocrystals has opened a new regime in plasmonics. We address both the technological and fundamental advances made possible by the realization of LSPRs in semiconductor nanocrystals. LSPRs were originally thought to be specific only to metallic nanostructures, but since their manifestation in semiconductor nanostructures, LSPRs are being seen as ubiquitous optical signatures of charge carriers. As fingerprints of a charge carrier collection, LSPRs of semiconductors are emerging as optical probes of processes that involve carrier dynamics, including redox reactions, electrochemistry, phase transitions, and photocatalysis. Unlike their electrical counterparts, LSPRs allow remote contactless probing and minimal device design. Ultrasmall semiconductor quantum dots are now enabling access to plasmon resonances of a handful of charge carriers, allowing us to ask fundamental questions regarding the lower limit of charge carriers needed to sustain a plasmon resonance, the emergence of a collective mode from a single-electron transition, and the effect of quantum confinement on plasmon resonances. These fundamental issues are discussed here, along with the need for new physical models required to capture the unique aspects of semiconductor LSPRs. PMID- 26270977 TI - Methane to Light Hydrocarbons via Oxidative Methane Coupling: Lessons from the Past to Search for a Selective Heterogeneous Catalyst. PMID- 26270978 TI - Moderately Strong Photoacid Dissociates in Alcohols with High Transient Concentration of the Proton-Transfer Contact Pair. AB - Proton transfer from strong photoacids to hydroxylic solvents is much under debate. Experimentally, the main issue stems from relaxation and diffusion processes that are concomitant with ultrafast proton transfer and blur population dynamics. To overcome this, we propose a fast photodissociation reaction that, however, proceeds slower than solvent relaxation. Fluorescence spectroscopy of the cationic photoacid 2-(1'-hydroxy-2'-naphtyl)benzimidazolium reveals a two stage mechanism: (a) reversible elementary proton transfer inside the solvent shell and (b) irreversible contact-pair splitting. The time evolution of the fluorescence signal is complex, yet this is explained quantitatively by simultaneous, spectrally overlapping emission of the acid, the conjugate base, and the contact proton-transfer pair. The latter attains high transient concentration in linear alcohols. Microscopic rate constants of dissociation are determined. PMID- 26270979 TI - Trajectory Entropy of Continuous Stochastic Processes at Equilibrium. AB - We propose to quantify the trajectory entropy of a dynamic system as the information content in excess of a free-diffusion reference model. The space-time trajectory is now the dynamic variable, and its path probability is given by the Onsager-Machlup action. For the time propagation of the overdamped Langevin equation, we solved the action path integral in the continuum limit and arrived at an exact analytical expression that emerged as a simple functional of the deterministic mean force and the stochastic diffusion. This work may have direct implications in chemical and phase equilibria, bond isomerization, and conformational changes in biological macromolecules as well transport problems in general. PMID- 26270981 TI - Dynamics of Gene Silencing in a Live Cell: Stochastic Resonance. AB - Binding of a specific siRNA to the target mRNA in a live cell (human breast cancer cell, MCF-7) is studied by confocal microscopy. The specific siRNA (labeled with a fluorophore, alexa 488) exhibits much higher intensity of fluorescence in the bound state than in the free (unbound) state. It is observed that repeated unbinding and rebinding of siRNA (to target mRNA) occur before gene silencing. 16 273 on-time periods (residence or dwell time of siRNA in bound form) are detected. They follow a strikingly simple pattern. All of the on-time periods are odd-integral multiples of 5.5 +/- 0.05 ms. This is ascribed to stochastic resonance. PMID- 26270980 TI - CH3NH3SnxPb(1-x)I3 Perovskite Solar Cells Covering up to 1060 nm. AB - We report photovoltaic performances of all-solid state Sn/Pb halide-based perovskite solar cells. The cell has the following composition: F-doped SnO2 layered glass/compact titania layer/porous titania layer/CH3NH3SnxPb(1 x)I3/regioregular poly(3-hexylthiophene-2,5-diyl). Sn halide perovskite itself did not show photovoltaic properties. Photovoltaic properties were observed when PbI2 was added in SnI2. The best performance was obtained by using CH3NH3Sn0.5Pb0.5I3 perovskite. 4.18% efficiency with open circuit voltage 0.42 V, fill factor 0.50, and short circuit current 20.04 mA/cm(2) are reported. The edge of the incident photon to current efficiency curve reached 1060 nm, which was 260 nm red-shifted compared with that of CH3NH3PbI3 perovskite solar cells. PMID- 26270982 TI - Conductance Switching and Photovoltaic Effect of Ru(II) Complex Molecular Junctions: Role of Complex Properties and the Metal/Molecule Interface. AB - The charge transport of Ru(II) complex molecular junctions, fabricated using a soft stamp-printing method, was investigated from 95 to 299 K under both dark and light conditions in order to explore the roles of the electrode/molecule interface and complex properties in the device performance. The junctions show asymmetric current-voltage characteristics with conductance switching and a photovoltaic effect at low temperature. The device performance depends greatly on the redox characteristics and built-in potential induced by electrode/molecule interface(s) and the molecular dipole. Our work may provide valuable information for the design of novel molecular electronics. PMID- 26270983 TI - Anomalous Interface and Surface Strontium Segregation in (La1-ySry)2CoO4+/ delta/La1-xSrxCoO3-delta Heterostructured Thin Films. AB - Heterostructured oxides have shown unusual electrochemical properties including enhanced catalytic activity, ion transport, and stability. In particular, it has been shown recently that the activity of oxygen electrocatalysis on the Ruddlesden-Popper/perovskite (La1-ySry)2CoO4+/-delta/La1-xSrxCoO3-delta heterostructure is remarkably enhanced relative to the Ruddlesden-Popper and perovskite constituents. Here we report the first atomic-scale structure and composition of (La1-ySry)2CoO4+/-delta/La1-xSrxCoO3-delta grown on SrTiO3. We observe anomalous strontium segregation from the perovskite to the interface and the Ruddlesden-Popper phase using direct X-ray methods as well as with ab initio calculations. Such Sr segregation occurred during the film growth, and no significant changes were found upon subsequent annealing in O2. Our findings provide insights into the design of highly active catalysts for oxygen electrocatalysis. PMID- 26270984 TI - Organometallic Halide Perovskites: Sharp Optical Absorption Edge and Its Relation to Photovoltaic Performance. AB - Solar cells based on organometallic halide perovskite absorber layers are emerging as a high-performance photovoltaic technology. Using highly sensitive photothermal deflection and photocurrent spectroscopy, we measure the absorption spectrum of CH3NH3PbI3 perovskite thin films at room temperature. We find a high absorption coefficient with particularly sharp onset. Below the bandgap, the absorption is exponential over more than four decades with an Urbach energy as small as 15 meV, which suggests a well-ordered microstructure. No deep states are found down to the detection limit of ~1 cm(-1). These results confirm the excellent electronic properties of perovskite thin films, enabling the very high open-circuit voltages reported for perovskite solar cells. Following intentional moisture ingress, we find that the absorption at photon energies below 2.4 eV is strongly reduced, pointing to a compositional change of the material. PMID- 26270985 TI - Optical Pumping of Poly(3-hexylthiophene) Singlet Excitons Induces Charge Carrier Generation. AB - The dynamics of high-energy excitons of poly(3-hexylthiophene) (P3HT) are shown to consist of torsional relaxation and exciton dissociation to form free carriers. In this work, we use pump-push-probe femtosecond transient absorption spectroscopy to study the highly excited states of P3HT in solution. P3HT excitons are generated using a pump pulse (400 nm) and allowed to relax to the lowest-lying excited state before re-excitation using a push pulse (900 or 1200 nm), producing high-energy excitons that decay back to the original excited state with both subpicosecond (0.16 ps) and picosecond (2.4 ps) time constants. These dynamics are consistent with P3HT torsional relaxation, with the 0.16 ps time constant assigned to ultrafast inertial torsional relaxation. Additionally, the signal exhibits an incomplete recovery, indicating dissociation of high-energy excitons to form charge carriers due to excitation by the push pulse. Our analysis indicates that charge carriers are formed with a yield of 11%. PMID- 26270988 TI - Human-Friendly Light-Emitting Diode Source Stimulates Broiler Growth. AB - Previous study and our laboratory have reported that short-wavelength (blue and green) light and combination stimulate broiler growth. However, short-wavelength stimuli could have negative effects on poultry husbandry workers. The present study was conducted to evaluate the effects of human-friendly yellow LED light, which is acceptable to humans and close to green light, on broiler growth. We also aimed to investigate the potential quantitative relationship between the wavelengths of light used for artificial illumination and growth parameters in broilers. After hatching, 360 female chicks ("Meihuang" were evenly divided into six lighting treatment groups: white LED strips (400-700 nm, WL); red LED strips (620 nm, RL); yellow LED strips (580 nm, YL); green LED strips (514 nm, GL); blue LED strips (455 nm, BL); and fluorescent strips (400-700 nm, FL). From 30 to 72 days of age, broilers reared under YL and GL were heavier than broilers treated with FL (P < 0.05). Broilers reared under YL obtained the similar growth parameters with the broilers reared under GL and BL (P > 0.05). Moreover, YL significantly improved feeding efficiency when compared with GL and BL at 45 and 60 days of age (P < 0.05). In addition, we found an age-dependent effect of light spectra on broiler growth and a quantitative relationship between LED light spectra (455 to 620 nm) and the live body weights of broilers. The wavelength of light (455 to 620 nm) was found to be negatively related (R2 = 0.876) to live body weight at an early stage of development, whereas the wavelength of light (455 to 620 nm) was found to be positively correlated with live body weight (R2 = 0.925) in older chickens. Our results demonstrated that human-friendly yellow LED light (YL), which is friendly to the human, can be applied to the broilers production. PMID- 26270989 TI - ASSESSMENT OF A LONG-TERM DEVELOPMENTAL RELATIONSHIP-BASED APPROACH IN CHILDREN WITH AUTISM SPECTRUM DISORDER. AB - 90 Italian children (72 boys, 18 girls) with a diagnosis of infantile autism (age range = 2.5-16.5 yr.) were assessed with a non-verbal intelligence test (Leiter R). The test was repeated 3 times in four years. The measures used were IQ and Fluid Reasoning (FR), as evaluation of inductive and deductive reasoning, and the Autism Diagnostic Observation Schedule (ADOS), indicative of the severity of autistic symptoms at the beginning and at the end of therapy. The increase in the average IQ and FR scores at retests demonstrates the effectiveness of a treatment that emphasizes the centrality of the relationship-based approach. Moreover, the FR score at intake was predictive of a significant decrease of ADOS scores after four years of treatment, and of the increase in IQ observed in later evaluations. The data support the hypothesis that a relationship-based intervention allows cognitive improvement regardless of the autism severity expressed in the ADOS score. PMID- 26270990 TI - MILITARY FAMILIES: MEASUREMENT OF COMMUNITY RESOURCE ADEQUACY. AB - Understanding features of community strength both on and off the military installation will help identify and address the needs of military families. This study introduced a measure to identify adequacy of community resources for military families. Using confirmatory factor analysis with data from 717 service users (M age = 37.3 yr., SD = 10.6) representing four large U.S. Army installations, two domains of community resource adequacy were identified: resources on the installation and resources off the installation. This measure could be used in health research with military families and in improving resources available to this population. PMID- 26270987 TI - Multiple Protein Kinases via Activation of Transcription Factors NF-kappaB, AP-1 and C/EBP-delta Regulate the IL-6/IL-8 Production by HIV-1 Vpr in Astrocytes. AB - Neurocognitive impairments affect a substantial population of HIV-1 infected individuals despite the success of anti-retroviral therapy in controlling viral replication. Astrocytes are emerging as a crucial cell type that might be playing a very important role in the persistence of neuroinflammation seen in patients suffering from HIV-1 associated neurocognitive disorders. HIV-1 viral proteins including Vpr exert neurotoxicity through direct and indirect mechanisms. Induction of IL-8 in microglial cells has been shown as one of the indirect mechanism through which Vpr reduces neuronal survival. We show that HIV-1 Vpr induces IL-6 and IL-8 in astrocytes in a time-dependent manner. Additional experiments utilizing chemical inhibitors and siRNA revealed that HIV-1 Vpr activates transcription factors NF-kappaB, AP-1 and C/EBP-delta via upstream protein kinases PI3K/Akt, p38-MAPK and Jnk-MAPK leading to the induction of IL-6 and IL-8 in astrocytes. We demonstrate that one of the mechanism for neuroinflammation seen in HIV-1 infected individuals involves induction of IL-6 and IL-8 by Vpr in astrocytes. Understanding the molecular pathways involved in the HIV-1 neuroinflammation would be helpful in the design of adjunct therapy to ameliorate some of the symptoms associated with HIV-1 neuropathogenesis. PMID- 26270991 TI - Accelerating a Mechanically Driven anti-Woodward-Hoffmann Ring Opening with a Polymer Lever Arm Effect. AB - Mechanical forces have previously been used to drive reactions along pathways that violate the orbital symmetry effects captured in the Woodward-Hoffmann rules. Here, we show that a polymer "lever arm effect" can provide a mechanical advantage in accelerating the symmetry forbidden disrotatory ring opening of benzocyclobutene (BCB). Addition of an alpha-E-alkene to the BCB mechanophore drops the force required to induce reactions on the ~0.1 s time scale of single molecule force spectroscopy experiments from 1370 to 920 pN. PMID- 26270992 TI - Rethinking Patient-Physician Communication of Biopsy Results--The Waiting Game. PMID- 26270993 TI - Professionalism and the environment: The influence of role models. PMID- 26270995 TI - Call for integrated approach to death education in UK medical schools. PMID- 26270996 TI - Peer and near-peer OSCE examiners. PMID- 26270997 TI - Balancing student- and tutor-guidance in problem-based curricula - Response to "Is the PBL generation of medical students reliant on Dr Google?" PMID- 26270998 TI - Alopecic Lesions on the Scalp in a Young Woman: A Quiz. PMID- 26270999 TI - Associations of diet quality with cognition in children - the Physical Activity and Nutrition in Children Study. AB - Evidence on the associations of dietary patterns with cognition in children is limited. Therefore, we investigated the associations of the Baltic Sea Diet Score (BSDS) and the Dietary Approaches to Stop Hypertension (DASH) score with cognition in children. The present cross-sectional study sample included 428 children aged 6-8 years (216 boys and 212 girls). The BSDS and the DASH score were calculated using data from 4 d food records, higher scores indicating better diet quality. Cognition was assessed by the Raven's Coloured Progressive Matrices (CPM) score, a higher score indicating better cognition. Among all children, the BSDS (standardised regression coefficient beta = 0.122, P =0.012) and the DASH score (beta = 0.121, P =0.015) were directly associated with the Raven's CPM score. Among boys, a lower BSDS (beta = 0.244, P< 0.001) and a lower DASH score (beta = 0.202, P= 0.003) were related to a lower Raven's CPM score. Boys in the lowest quartile of the BSDS (22.5 v. 25.3, P= 0.029) and the DASH score (22.4 v. 25.7, P= 0.008) had a lower Raven's CPM score than those in the highest quartile of the corresponding score. Among girls, the BSDS or the DASH score were not associated with cognition. In conclusion, a poorer diet quality was associated with worse cognition in children, and the relationship was stronger in boys than in girls. PMID- 26271000 TI - Evaluation of the Double Agar Gel Immunodiffusion Test and of the Enzyme-Linked Immunosorbent Assay in the Diagnosis and Follow-Up of Patients with Chronic Pulmonary Aspergillosis. AB - The diagnosis of chronic pulmonary aspergillosis (CPA) depends on the radiologic image and the identification of specific antibodies. The present study aimed to evaluate accuracy parameters of enzyme-linked immunosorbent assay (ELISA) and of the determination of serum galactomannan level in the diagnosis of patients with CPA, comparing these results with the double agar gel immunodiffusion (DID) test. In addition, the prevalence of cross-reactivity and the serological progression after treatment were evaluated by comparing DID and ELISA. Six study groups were formed: G1: 22 patients with CPA, 17 of whom had Aspergillus fungus ball, one chronic cavitary pulmonary aspergillosis (CCPA) and four chronic fibrosing pulmonary aspergillosis (CFPA); G2: 28 patients with pulmonary tuberculosis (TB); G3: 23 patients with histoplasmosis (HST); G4: 50 patients with paracoccidioidomycosis (PCM); G5: 20 patients with cryptococcosis (CRC); and G6: 200 healthy controls. Serum antibodies were measured by DID and ELISA, with two antigen preparations--Aspergillus fumigatus (DID1, ELISA1) and a pool of A. fumigatus, A. flavus and A. niger antigens (DID2, ELISA2). The Platelia Aspergillus Enzyme Immunoassay (EIA) kit was used to measure galactomannan. The cut-off points of ELISA were determined for each antigen preparation and for the 95% and 99% confidence intervals. Despite the low sensitivity, DID was the technique of choice due to its specificity, positive and negative predictive values and positive likelihood ratio-especially with the antigen pool and due to the low frequency of cross-reactivity. ELISA1 and a 0.090 cut-off showed high sensitivity, specificity and negative predictive value, but a high frequency of cross-reactivity with CRC. The best degree of agreement was observed between ELISA1 and ELISA2. The detection of serum galactomannan showed high sensitivity, comparable to ELISA2. The immunodiffusion test showed an excellent relationship with the progression after treatment, which made it the reaction of choice for patient follow-up. PMID- 26271001 TI - Diacyltransferase Activity and Chain Length Specificity of Mycobacterium tuberculosis PapA5 in the Synthesis of Alkyl beta-Diol Lipids. AB - Although they are classified as Gram-positive bacteria, Corynebacterineae possess an asymmetric outer membrane that imparts structural and thereby physiological similarity to more distantly related Gram-negative bacteria. Like lipopolysaccharide in Gram-negative bacteria, lipids in the outer membrane of Corynebacterineae have been associated with the virulence of pathogenic species such as Mycobacterium tuberculosis (Mtb). For example, Mtb strains that lack long, branched-chain alkyl esters known as dimycocerosates (DIMs) are significantly attenuated in model infections. The resultant interest in the biosynthetic pathway of these unusual virulence factors has led to the elucidation of many of the steps leading to the final esterification of the alkyl beta-diol, phthiocerol, with branched-chain fatty acids known as mycocerosates. PapA5 is an acyltransferase implicated in these final reactions. Here, we show that PapA5 is indeed the terminal enzyme in DIM biosynthesis by demonstrating its dual esterification activity and chain-length preference using synthetic alkyl beta-diol substrate analogues. By applying these analogues to a series of PapA5 mutants, we also revise a model for the substrate binding within PapA5. Finally, we demonstrate that the Mtb Ser/Thr kinases PknB and PknE modify PapA5 on three overlapping Thr residues and that a fourth Thr is unique to PknE phosphorylation. These results clarify the DIM biosynthetic pathway and indicate post translational modifications that warrant further elucidation for their roles in the regulation of DIM biosynthesis. PMID- 26271002 TI - Rapid access palliative radiation therapy programs: an efficient model of care. AB - Palliating symptoms of advanced and metastatic cancers are one of the most common indications for radiation therapy (RT), and the demand for palliative RT is increasing. Dedicated rapid access palliative RT programs improve access to care, and can deliver RT in a more efficient and evidence-based manner than standard RT programs. In this narrative review, we discuss the role of palliative RT in comprehensive cancer care, and challenges that have faced patients trying to access it. We describe how rapid access programs developed to address these challenges and provide an overview of dedicated programs worldwide. Finally, we show how these programs can serve as models for multidisciplinary care and education, and sources of exciting research opportunities in clinical care and advanced technologies. PMID- 26271003 TI - Effect of pregnancy on the disposition of 2,2',3,5',6-pentachlorobiphenyl (PCB 95) atropisomers and their hydroxylated metabolites in female mice. AB - Chiral PCBs, such as PCB 95, are developmental neurotoxicants that undergo atropisomeric enrichment in nonpregnant adult mice. Because pregnancy is associated with changes in hepatic cytochrome P450 enzyme activity as well as lipid disposition and metabolism, this study investigates the effect of pregnancy on the maternal disposition of chiral PCBs. Female C57BL/6 mice (8 weeks old) were dosed daily beginning 2 weeks prior to conception and continuing throughout gestation and lactation (56 days total) with racemic PCB 95 (0, 0.1, 1.0, or 6.0 mg/kg body wt/day) in peanut butter. Levels and chiral signatures of PCB 95 and its hydroxylated metabolites (OH-PCBs) were determined in adipose, blood, brain, and liver. Tissue levels of PCB 95 increased 4- to 12-fold with increasing dose, with considerable enrichment of the second eluting atropisomer in all tissues (EF range 0.11 to 0.26). OH-PCBs displayed atropisomeric enrichment in blood and liver but were not detected in adipose and brain. Levels of PCB 95 and its metabolites were 2- to 11-fold lower in pregnant dams relative to those previously reported in nonpregnant age-matched female mice; however, PCB 95 and OH-PCB profiles and chiral signatures were similar between both studies. In contrast, human brain samples contained racemic PCB 95 residues (EF = 0.50). These results demonstrate that changes in cytochrome P450 enzyme activity and lipid disposition during pregnancy reduce the PCB body burden in dams but do not affect metabolite profiles or chiral signatures. The differences in chiral signatures between mice and humans suggest species-specific differences in atropisomeric disposition, the toxicological significance of which remains to be determined. PMID- 26271004 TI - BAC transgenic zebrafish reveal hypothalamic enhancer activity around obesity associated SNP rs9939609 within the human FTO gene. AB - Single Nucleotide Polymorphisms in FTO intron 1 have been associated with obesity risk, leading to the hypothesis that FTO is the obesity-related gene. However, other studies have shown that the FTO gene is part of the regulatory domain of the neighboring IRX3 gene and that enhancers in FTO intron 1 regulate IRX3. While Irx3 activity was shown to be necessary in the hypothalamus for the metabolic function of Irx3 in mouse, no enhancers with hypothalamic activity have been demonstrated in the risk-associated region within FTO. In order to identify potential enhancers at the human FTO locus in vivo, we tested regulatory activity in FTO intron 1 using BAC transgenesis in zebrafish. A minimal gata2 promoter-GFP cassette was inserted 1.3 kb upstream of the obesity associated SNP rs9939609 in a human FTO BAC plasmid. In addition to the previously identified expression domains in notochord and kidney, human FTO BAC:GFP transgenic zebrafish larvae expressed GFP in the ventral posterior tuberculum, the posterior hypothalamus and the anterior brainstem, which are also expression domains of zebrafish irx3a. In contrast, an in-frame insertion of a GFP cassette at the FTO start codon resulted in weak ubiquitous GFP expression indicating that the promoter of FTO does likely not react to enhancers located in the obesity risk-associated region. PMID- 26271006 TI - Active intracellular transport in metastatic cells studied by spatial light interference microscopy. AB - Spatiotemporal patterns of intracellular transport are very difficult to quantify and, consequently, continue to be insufficiently understood. While it is well documented that mass trafficking inside living cells consists of both random and deterministic motions, quantitative data over broad spatiotemporal scales are lacking. We studied the intracellular transport in live cells using spatial light interference microscopy, a high spatiotemporal resolution quantitative phase imaging tool. The results indicate that in the cytoplasm, the intracellular transport is mainly active (directed, deterministic), while inside the nucleus it is both active and passive (diffusive, random). Furthermore, we studied the behavior of the two-dimensional mass density over 30 h in HeLa cells and focused on the active component. We determined the standard deviation of the velocity distribution at the point of cell division for each cell and compared the standard deviation velocity inside the cytoplasm and the nucleus. We found that the velocity distribution in the cytoplasm is consistently broader than in the nucleus, suggesting mechanisms for faster transport in the cytosol versus the nucleus. Future studies will focus on improving phase measurements by applying a fluorescent tag to understand how particular proteins are transported inside the cell. PMID- 26271005 TI - Alterations in Thyroid Hormones Due to Increased Intraabdominal Pressure in Rats. AB - PURPOSE: Although the effects of increased intraabdominal pressure on the abdominal organs are well known, there is a limited data regarding its effects on the thyroid hormones. The aim of this study is to investigate the changes in thyroid hormone profiles during stress endocrine response induced by increased intraabdominal pressure, which was obtained by pneumoperitoneum in rats. MATERIALS AND METHODS: A hundred-fifty female wistar albino rats were divided into three main groups, according to intraabdominal pressure applied; Control (Group 1), (n:30), low pressure, 15 mmHg, (Groups 2 and 3), (n:60), and high intraabdominal pressure, 25 mmHg, (Groups 4 and 5), (n:60) groups. Groups 2, 3, 4, 5 were divided into three subgroups separately, according to duration of intraabdominal pressure. Rats in Groups 3 and 5 were decompressed at the end of times indicated (15th, 30th, and 45th min) and blood samples were obtained. Whereas blood samples from Groups 2 and 4 were drawn without decompression at the end of times indicated. Measurements included thyroid stimulating hormone, cortisole, vasopressin, adrenocorticotropic hormone, triiodotronin and thyroxin. RESULT: Our study revealed that blood TSH levels reduce and free T3 and T4 levels increase in case of prolonged intraabdominal pressure increase that cause abdominal compartment syndrome. The change in blood thyroid hormone levels are encountered prominently on 30th and 45th min. CONCLUSION: Secretion of vasopressin, adrenocorticotropic Hormone and cortisol increases with increasing intraabdominal pressure. At high pressures, thyroid stimulating hormone secretion decreases while the secretion of triiodotronin increases. The effect of this case on the clinical findings has not been fully clarified yet and it needs further studies to clarify underlying mechanism. In this perspective, the findings of this study may be used in further clinical and experimental studies. PMID- 26271007 TI - Vantage Sensitivity: Environmental Sensitivity to Positive Experiences as a Function of Genetic Differences. AB - A large number of gene-environment interaction studies provide evidence that some people are more likely to be negatively affected by adverse experiences as a function of specific genetic variants. However, such "risk" variants are surprisingly frequent in the population. Evolutionary analysis suggests that genetic variants associated with increased risk for maladaptive development under adverse environmental conditions are maintained in the population because they are also associated with advantages in response to different contextual conditions. These advantages may include (a) coexisting genetic resilience pertaining to other adverse influences, (b) a general genetic susceptibility to both low and high environmental quality, and (c) a coexisting propensity to benefit disproportionately from positive and supportive exposures, as reflected in the recent framework of vantage sensitivity. After introducing the basic properties of vantage sensitivity and highlighting conceptual similarities and differences with diathesis-stress and differential susceptibility patterns of gene-environment interaction, selected and recent empirical evidence for the notion of vantage sensitivity as a function of genetic differences is reviewed. The unique contribution that the new perspective of vantage sensitivity may make to our understanding of social inequality will be discussed after suggesting neurocognitive and molecular mechanisms hypothesized to underlie the propensity to benefit disproportionately from benevolent experiences. PMID- 26271009 TI - Ngn1 inhibits astrogliogenesis through induction of miR-9 during neuronal fate specification. AB - It has been postulated that a proneural factor, neurogenin 1 (Ngn1), simultaneously activates the neurogenic program and inhibits the alternative astrogliogenic program when specifying the neuronal fate. While Ngn1 substantially suppresses the activation of the astrogliogenic Jak-Stat pathway, the underlying molecular mechanism was unknown. Here, by employing in vivo and in vitro approaches, we report that Ngn1 binds to the promoter of a brain-enriched microRNA, miR-9, and activates its expression during neurogenesis. Subsequently, our in vitro study showed that miR-9 directly targets mRNAs of Lifr-beta, Il6st (gp130), and Jak1 to down-regulate these critical upstream components of the Jak Stat pathway, achieving inhibition of Stat phosphorylation and consequently, suppression of astrogliogenesis. This study revealed Ngn1 modulated non-coding RNA epigenetic regulation during cell fate specifications. PMID- 26271010 TI - Longitudinal analysis of Plasmodium sporozoite motility in the dermis reveals component of blood vessel recognition. AB - Malaria infection starts with injection of Plasmodium sporozoites by an Anopheles mosquito into the skin of the mammalian host. How sporozoites locate and enter a blood vessel is a critical, but poorly understood process. In this study, we examine sporozoite motility and their interaction with dermal blood vessels, using intravital microscopy in mice. Our data suggest that sporozoites exhibit two types of motility: in regions far from blood vessels, they exhibit 'avascular motility', defined by high speed and less confinement, while in the vicinity of blood vessels their motility is more constrained. We find that curvature of sporozoite tracks engaging with vasculature optimizes contact with dermal capillaries. Imaging of sporozoites with mutations in key adhesive proteins highlight the importance of the sporozoite's gliding speed and its ability to modulate adhesive properties for successful exit from the inoculation site. PMID- 26271008 TI - BAG2 promotes tumorigenesis through enhancing mutant p53 protein levels and function. AB - Tumor suppressor p53 is the most frequently mutated gene in tumors. Many mutant p53 (mutp53) proteins promote tumorigenesis through the gain-of-function (GOF) mechanism. Mutp53 proteins often accumulate to high levels in tumors, which is critical for mutp53 GOF. Its underlying mechanism is poorly understood. Here, we found that BAG2, a protein of Bcl-2 associated athanogene (BAG) family, promotes mutp53 accumulation and GOF in tumors. Mechanistically, BAG2 binds to mutp53 and translocates to the nucleus to inhibit the MDM2-mutp53 interaction, and MDM2 mediated ubiquitination and degradation of mutp53. Thus, BAG2 promotes mutp53 accumulation and GOF in tumor growth, metastasis and chemoresistance. BAG2 is frequently overexpressed in tumors. BAG2 overexpression is associated with poor prognosis in patients and mutp53 accumulation in tumors. These findings revealed a novel and important mechanism for mutp53 accumulation and GOF in tumors, and also uncovered an important role of BAG2 in tumorigenesis through promoting mutp53 accumulation and GOF. PMID- 26271013 TI - Acute haemothorax after ruptured ectopic pregnancy. PMID- 26271012 TI - Polyhydramnios associated with Prader-Willi syndrome. PMID- 26271011 TI - Self-Assembly of a Multifunctional Lipid With Core-Shell Dendrimer DNA Nanoparticles Enhanced Efficient Gene Delivery at Low Charge Ratios into RPE Cells. AB - Development of safe and effective gene delivery systems is essential in treating ocular genetic disorders. A hybrid nonviral system composed of a multifunctional lipid ECO and a G4 nanoglobule was designed for efficient gene delivery into RPE cells at low charge ratios. This system formed stable DNA nanoparticles at low N/P ratios, exhibited low cytotoxicity, and induced higher GFP expression in ARPE 19 cells at N/P = 6. The hybrid nanoparticles mediated significant reporter gene GFP expression ex-vivo in the retina from wild type C57 mice and in vivo in BALB/c mice. These hybrid nanoparticles are promising for in vitro and in vivo gene delivery at low charge ratios. PMID- 26271014 TI - Why babies - What Australian mothers say. AB - Earlier studies, mostly overseas, have explored the reasoning and thought processes underlying women's desires to conceive. A retrospective qualitative study was conducted to explore the motivations and anxieties of an Australian sample of women proceeding to a pregnancy and to explore their decision-making process. Twenty women over 18 years old who had one or more successful pregnancies and were recruited from a tertiary centre and private clinics, completed a questionnaire and a semi-structured interview. Thematic analysis was applied to the data. Multiple factors motivated women to proceed to a pregnancy and including influences arising from society or existing personal relationships, goals and desired experiences for parenthood and innate drives and reproductive related issues. The motivations of an urban Australian sample to proceed to a pregnancy differed little from studies elsewhere. This knowledge may assist in dealing with the concerns that underlie any pregnancy allowing for better obstetric management. PMID- 26271015 TI - Reference dosimetry in the presence of magnetic fields: conditions to validate Monte Carlo simulations. AB - With the advent of MRI-guided radiotherapy, reference dosimetry must be thoroughly addressed to account for the effects of the magnetic field on absorbed dose to water and on detector dose response. While Monte Carlo plays an essential role in reference dosimetry, it is also crucial for determining quality correction factors in these new conditions. The Fano cavity test is recognized as fundamental to validate Monte Carlo transport algorithms. In the presence of magnetic fields, it is necessary to define special conditions under which such a test can be performed. The present theoretical study proposes two conditions in which the validity of Fano's theorem is demonstrated in the presence of a magnetic field and the analytic expression of energy deposition is verified. It is concluded that the proposed conditions form a valid basis for two types of Fano cavity tests in the presence of a magnetic field. PMID- 26271016 TI - Isotopic studies of the ammonia decomposition reaction mediated by sodium amide. AB - We demonstrate that the ammonia decomposition reaction catalysed by sodium amide proceeds under a different mechanism to ammonia decomposition over transition metal catalysts. Isotopic variants of ammonia and sodium amide reveal a significant kinetic isotope effect in contrast to the nickel-catalysed reaction where there is no such effect. The bulk composition of the catalyst is also shown to affect the kinetics of the ammonia decomposition reaction. PMID- 26271017 TI - Synergistic Effect of Superhydrophobicity and Oxidized Layers on Corrosion Resistance of Aluminum Alloy Surface Textured by Nanosecond Laser Treatment. AB - We report a new efficient method for fabricating a superhydrophobic oxidized surface of aluminum alloys with enhanced resistance to pitting corrosion in sodium chloride solutions. The developed coatings are considered very prospective materials for the automotive industry, shipbuilding, aviation, construction, and medicine. The method is based on nanosecond laser treatment of the surface followed by chemisorption of a hydrophobic agent to achieve the superhydrophobic state of the alloy surface. We have shown that the surface texturing used to fabricate multimodal roughness of the surface may be simultaneously used for modifying the physicochemical properties of the thick surface layer of the substrate itself. Electrochemical and wetting experiments demonstrated that the superhydrophobic state of the metal surface inhibits corrosion processes in chloride solutions for a few days. However, during long-term contact of a superhydrophobic coating with a solution, the wetted area of the coating is subjected to corrosion processes due to the formation of defects. In contrast, the combination of an oxide layer with good barrier properties and the superhydrophobic state of the coating provides remarkable corrosion resistance. The mechanisms for enhancing corrosion protective properties are discussed. PMID- 26271018 TI - A Web-Based Early Intervention Can Prevent Long-Term PTS Reactions in Children With High Initial Distress Following Accidental Injury. AB - The present study explored the targeting of a preventative information provision intervention delivered to children following accidental injury by assessing the impact of initial traumatic distress on response to treatment. Analyses were based on baseline and 6-month outcome of child traumatic stress in a control (n = 28) and an intervention group (n = 31). Moderation of treatment outcome by initial levels of child traumatic stress was assessed through multiple hierarchical regression analyses. Results indicated the interaction between treatment provision and initial level of posttraumatic stress significantly predicted 6-month outcome (beta = -.42, p = .019). When initial distress was high, children in the control group demonstrated an increase in trauma symptoms, and had significantly higher trauma symptoms at follow-up than those in the treatment group (d = 0.94, p = .008). When initial distress was not elevated, no significant differences were noted between the groups. These results indicate that a preventative early intervention may be best targeted at children presenting with the specific risk factor of high initial distress. PMID- 26271019 TI - Posttraumatic Stress Disorder and Barriers to Care in Eastern Cape Province, South Africa. AB - A range of barriers to seeking mental health care in low- and middle-income countries has been investigated. Little, however, is known of the barriers to care and help-seeking behavior among people with posttraumatic stress disorder (PTSD) in low- and middle-income countries. This was a population-based study including 977 people aged 18-40 years from the Eastern Cape Province in South Africa. Current PTSD was assessed by using a diagnostic questionnaire (Mini International Psychiatric Interview). An additional questionnaire captured socioeconomic and health-related data. The prevalence of current PTSD was 10.8%. Only 48.1% of people with current PTSD accessed health care services. Younger people aged 18 to 29 years were less likely to seek health care, OR = 0.36, 95% CI [0.15, 0.85]. People earning a salary or wage, OR = 2.91, 95% CI [1.26, 6.71]; and those with tuberculosis, OR = 11.63, 95% CI [1.42, 95.56], were more likely to seek health care. A range of barriers to seeking care were identified, the most striking being stigma and a lack of knowledge regarding the nature and treatment of mental illness. People with current PTSD may seek help for other health concerns and brief screening means those affected may be readily identified. PMID- 26271021 TI - Preliminary evaluation of military, commercial and novel skin decontamination products against a chemical warfare agent simulant (methyl salicylate). AB - Rapid decontamination is vital to alleviate adverse health effects following dermal exposure to hazardous materials. There is an abundance of materials and products which can be utilised to remove hazardous materials from the skin. In this study, a total of 15 products were evaluated, 10 of which were commercial or military products and five were novel (molecular imprinted) polymers. The efficacies of these products were evaluated against a 10 ul droplet of 14C-methyl salicylate applied to the surface of porcine skin mounted on static diffusion cells. The current UK military decontaminant (Fuller's earth) performed well, retaining 83% of the dose over 24 h and served as a benchmark to compare with the other test products. The five most effective test products were Fuller's earth (the current UK military decontaminant), Fast-Act(r) and three novel polymers [based on itaconic acid, 2-trifluoromethylacrylic acid and N,N methylenebis(acrylamide)]. Five products (medical moist-free wipes, 5% FloraFreeTM solution, normal baby wipes, baby wipes for sensitive skin and DiphoterineTM) enhanced the dermal absorption of 14C-methyl salicylate. Further work is required to establish the performance of the most effective products identified in this study against chemical warfare agents. PMID- 26271020 TI - Adrenomedullin--A New Marker in Febrile Neutropenia: Comparison With CRP and Procalcitonin. AB - In this study, we aimed to determine serum adrenomedullin levels and compare them with levels of C-reactive protein (CRP) and procalcitonin (PCT). Cancer patients aged 0-18 years who experienced febrile neutropenia attacks were included in the study. Adrenomedullin, CRP, and PCT were analyzed at admission, day 3, and days 7 10 later. Fifty episodes of febrile neutropenia that developed in 37 patients were analyzed in this study. The mean age of the patients was 7.5 +/- 4.7 (1-18) years. The patients had leukemia (73%), solid tumors (19%), and lymphoma (8%). The percentages of the patients in the clinically documented infection (CDI), fever of unknown origin (FUO), sepsis, and microbiological documented infection (MDI) categories were 34%, 34%, 20%, and 12%, respectively. During the study period, four patients were lost. In the MDI group, adrenomedullin levels on day 3 were significantly higher than those in the CDI and FUO groups. PCT levels were significantly higher in the sepsis group than those in the CDI group at admission, day 3, and days 7-10. In the sepsis group, PCT levels on days 7-10 days were significantly higher than those in the sepsis group. PCT values from the deceased patients on days 7-10 were significantly higher than those from patients who survived. CRP levels did not differ significantly among the febrile neutropenia groups. First, in our study, adrenomedullin was used as a biomarker in the febrile neutropenia episodes of children with cancer. Among adrenomedullin, CRP, and PCT, procalcitonin demonstrates the highest correlation with the severity of infection. PMID- 26271022 TI - In-Depth Survey of Scarring and Distress in Patients Undergoing Bilateral Axillo Breast Approach Robotic Thyroidectomy or Conventional Open Thyroidectomy. AB - PURPOSE: Oncologic and surgical outcomes of bilateral axillo-breast approach (BABA) robotic thyroidectomy (RoT) are comparable with those of open thyroidectomy (OT). We compared degree of scarring and psychological/physical distress between OT and BABA RoT. MATERIALS AND METHODS: Study included 129 cases of thyroidectomy (78 OT, 51 BABA RoT). Patients were evaluated by psychology consultant using 5-point scale questionnaire. RESULTS: BABA RoT was associated with lower degree of scarring than OT (7.8 vs. 11.7, P<0.001). Psychological distress immediately after operation and during surveillance period was higher in OT than in BABA RoT (3.1 vs. 2.6, P=0.009 and 2.4 vs. 1.9, P<0.001). Physical distress (pain and exercise limitation) did not differ between groups (2.5 vs. 2.6, P=0.321 and 2.0 vs. 1.9, P=0.0175). CONCLUSIONS: BABA RoT was associated with less scarring and psychological distress than OT. BABA RoT might be alternative for patients who are concerned about neck scar. PMID- 26271023 TI - Methylene Blue or Upper GI, Which is More Effective for Detecting Leaks in Gastric Bypass Patients? AB - BACKGROUND: Postoperative leaks from the staple lines are a serious complication after laparoscopic Roux-en-Y gastric bypass (RYGB) that results in morbidity and could even lead to mortality. Bariatric surgeons have several tools to assess this adversity. There have been debates as to which method is more superior and furthermore whether these methods should be routinely or selectively used. The aim of our study is to evaluate and compare whether methylene blue or upper gastrointestinal (UGI) study is more effective in detecting an anastomotic leak after RYGB. MATERIALS AND METHODS: Between May 2013 and March 2014, 119 patients underwent laparoscopic RYGB. Linear staplers were used to create the gastrojejunostomy and the jejunojejunostomy. All patients underwent routine UGI studies and methylene blue challenges on postoperative day 1. A retrospective review of a prospectively collected database was performed for all patients. RESULTS: Of the 105 patients in this study there were 83 females (79.0%) and 22 males (21.0%). Mean age was 45.2+/-10.7 years (range, 21 to 66 y) and mean preoperative body mass index was 47.8+/-7.9 kg/m (range, 35.7 to 76.4 kg/m) at the time of procedure. Mean length of hospital stay was 3.2+/-6.0 days (range, 1 to 53 d).Four (3.8%) patients were found to have leaks postoperatively, but no leakage was detected in any of the initial routine UGI studies or methylene blue challenges. Both patient were diagnosed with clinical signs and underwent oversewing of the leak sites. CONCLUSIONS: UGI studies and methylene blue challenges had no significant difference in detecting a postoperative leak. Furthermore, these tests may have limited utility and may warrant adjuncts to aid in leak detection. PMID- 26271024 TI - Efficacy of Endoscopic Mucosal Resection for Management of Small Duodenal Neuroendocrine Tumors. AB - BACKGROUND: Endoscopic mucosal resection (EMR) for small (<20 mm) duodenal neuroendocrine tumors (NETs) remains controversial because of their rarity. MATERIALS AND METHODS: This is a retrospective cohort study of patients with surgically or endoscopically resected duodenal NETs from 2001 to 2011. The primary outcome is the rate of disease-free status following resection. A secondary outcome is the sensitivity of endoscopic ultrasound (EUS) in determining NET appropriateness for EMR. RESULTS: Thirty patients underwent resection of duodenal NETs (EMR 20, surgery 10). Tumor was present at the margins in 40% of EMR-resected NETs and 10% of surgically resected NETs. Five patients who underwent EMR had residual disease treated with repeat EMR (3) and surgery (2). EUS demonstrated 96% sensitivity in determining lesions limited to the submucosa. CONCLUSIONS: EMR for small duodenal NETs can be a safe and effective alternative to surgery in carefully selected patients. EUS is a useful adjunct in determining depth of invasion for duodenal NETs. PMID- 26271025 TI - Bioinspired Hybrid White Light-Emitting Diodes. AB - The first bioinspired hybrid white-light-emitting diodes (bio-HLEDs) featuring protein cascade coatings are presented. For easy fabrication a new strategy to stabilize proteins in rubber-like material was developed. The synergy between the excellent features of fluorescent proteins and the easily processed rubber produces bio-HLEDs with less than 10% loss in luminous efficiency over 100 hours. PMID- 26271026 TI - Red pill, blue pill: reflections on the emerging large vessel stroke 'market'. PMID- 26271027 TI - Association of a single nucleotide polymorphism in the 5' upstream region of the porcine myosin heavy chain 4 gene with meat quality traits in pigs. AB - We identified a potential molecular marker associated with meat quality traits in the myosin heavy chain 4, MYH4 gene of Landrace pigs. Sequencing revealed a single nucleotide polymorphism (SNP; g.-1398G>T) in the 5' upstream region of MYH4. It was significantly associated with the number of type IIa muscle fibers and water-holding capacity based on filter-paper fluid uptake. The GG genotype groups had a greater number of type IIa fibers and a larger area composed of type IIa fibers than the other genotype group (P = 0.004 and P = 0.061, respectively). Expression level of MYH4 gene in the genotype TT or GT was higher than in genotype of GG (P < 0.0001). The T allele may enhance expression level of MYH4 gene and then the portion of IIb type fiber in the muscle be increased by the T allelle. Therefore, we suggest that the g.-1398G>T in the 5' upstream region of the porcine MYH4 may be used as a molecular marker for meat quality traits, although its functional effect is not defined yet. PMID- 26271028 TI - Clinical Characteristics and Outcomes Are Similar in ARDS Diagnosed by Oxygen Saturation/Fio2 Ratio Compared With Pao2/Fio2 Ratio. AB - BACKGROUND: Oxygen saturation as measured by pulse oximetry/Fio2 (SF) ratio is highly correlated with the Pao2/Fio2 (PF) ratio in patients with ARDS. However, it remains uncertain whether SF ratio can be substituted for PF ratio for diagnosis of ARDS and whether SF ratio might identify patients who are systemically different from patients diagnosed by PF ratio. METHODS: We conducted a secondary analysis of a large observational prospective cohort study. Patients were eligible if they were admitted to the medical ICU and fulfilled the Berlin definition of ARDS with hypoxemia criteria using either the standard PF threshold (PF ratio <= 300) or a previously published SF threshold (SF ratio <= 315). RESULTS: Of 362 patients with ARDS, 238 (66%) received a diagnosis by PF ratio and 124 (34%) by SF ratio. In a small group of patients who received diagnoses of ARDS by SF ratio who had arterial blood gas measurements on the same day (n = 10), the PF ratio did not meet ARDS criteria. There were no major differences in clinical characteristics or comorbidities between groups with the exception of APACHE (Acute Physiology and Chronic Health Evaluation) II scores, which were higher in the group diagnosed by PF ratio. However, this difference was no longer apparent when arterial blood gas-dependent variables (pH, Pao2) were removed from the APACHE II score. There were also no differences in clinical outcomes including duration of mechanical ventilation (mean, 7 days in both groups; P = .25), duration of ICU stay (mean, 10 days vs 9 days in PF ratio vs SF ratio; P = .26), or hospital mortality (36% in both groups, P = .9). CONCLUSIONS: Patients with ARDS diagnosed by SF ratio have very similar clinical characteristics and outcomes compared with patients diagnosed by PF ratio. These findings suggest that SF ratio could be considered as a diagnostic tool for early enrollment into clinical trials. PMID- 26271029 TI - Developing "Care Assistant": A smartphone application to support caregivers of children with acute lymphoblastic leukaemia. AB - Acute lymphoblastic leukaemia (ALL) is the most common childhood malignancy. Caring for children with ALL is an uncommon experience for parents without medical training. They urgently need professional assistance when their children are recovering at home. This paper documents the process of developing an Android application (app) "Care Assistant" for family caregivers of children with ALL. Key informant interviews and focus group studies were used before programming the app. The key informants and focus group members included: caregivers of children with ALL, cancer care physicians and nurses, and software engineers. We found several major challenges faced by caregivers: limited access to evidence-based clinic information, lack of financial and social assistance, deficient communications with doctors or nurses, lack of disease-related knowledge, and inconvenience of tracking treatments and testing results. This feedback was used to develop "Care Assistant". This app has eight modules: personal information, treatment tracking, family care, financial and social assistance, knowledge centre, self-assessment questionnaires, interactive platform, and reminders. We have also developed a web-based administration portal to manage the app. The usability and effectiveness of "Care Assistant" will be evaluated in future studies. PMID- 26271030 TI - Correction: Infection with Soil-Transmitted Helminths Is Associated with Increased Insulin Sensitivity. PMID- 26271031 TI - Estradiol regulates human QT-interval: acceleration of cardiac repolarization by enhanced KCNH2 membrane trafficking. AB - BACKGROUND: Modulation of cardiac repolarization by sexual hormones is controversial and hormonal effects on ion channels remain largely unknown. In the present translational study, we therefore assessed the relationship between QTc duration and gonadal hormones and studied underlying mechanisms. METHODS AND RESULTS: We measured hormone levels and QTc intervals in women during clomiphene stimulation for infertility and women before, during, and after pregnancy. Three heterozygous LQT-2 patients (KCNH2-p.Arg752Pro missense mutation) and two unaffected family members additionally were studied during their menstrual cycles. A comprehensive cellular and molecular analysis was done to identify the mechanisms of hormonal QT-interval regulation. High estradiol levels, but neither progesterone nor estradiol/progesterone ratio, inversely correlated with QTc. Consistent with clinical data, in vitro estradiol stimulation (60 pmol/L, 48 h) enhanced IKCNH2. This increase was mediated by estradiol receptor-alpha-dependent promotion of KCNH2-channel trafficking to the cell membrane. To study the underlying mechanism, we focused on heat-shock proteins. The heat-shock protein 90 (Hsp90) inhibitor geldanamycin abolished estradiol-induced increase in IKCNH2. Geldanamycin had no effect on KCNH2 transcription or translation; nor did it affect expression of estradiol receptors and chaperones. Estradiol enhanced the physical interaction of KCNH2-channel subunits with heat-shock proteins and augmented ion-channel trafficking to the membrane. CONCLUSION: Elevated estradiol levels were associated with shorter QTc intervals in healthy women and female LQT 2 patients. Estradiol acts on KCNH2 channels via enhanced estradiol-receptor alpha-mediated Hsp90 interaction, augments membrane trafficking and thereby increases repolarizing current. These results provide mechanistic insights into hormonal control of human ventricular repolarization and open novel therapeutic avenues. PMID- 26271032 TI - A Single-Strand Annealing Protein Clamps DNA to Detect and Secure Homology. AB - Repair of DNA breaks by single-strand annealing (SSA) is a major mechanism for the maintenance of genomic integrity. SSA is promoted by proteins (single-strand annealing proteins [SSAPs]), such as eukaryotic RAD52 and lambda phage Redbeta. These proteins use a short single-stranded region to find sequence identity and initiate homologous recombination. However, it is unclear how SSAPs detect homology and catalyze annealing. Using single-molecule experiments, we provide evidence that homology is recognized by Redbeta monomers that weakly hold single DNA strands together. Once annealing begins, dimerization of Redbeta clamps the double-stranded region and nucleates nucleoprotein filament growth. In this manner, DNA clamping ensures and secures a successful detection for DNA sequence homology. The clamp is characterized by a structural change of Redbeta and a remarkable stability against force up to 200 pN. Our findings not only present a detailed explanation for SSAP action but also identify the DNA clamp as a very stable, noncovalent, DNA-protein interaction. PMID- 26271033 TI - Biochemical and Immunological Characterization of Truncated Fragments of the Receptor-Binding Domains of C. difficile Toxin A. AB - Clostridium difficile is an emerging pathogen responsible for opportunistic infections in hospitals worldwide and is the main cause of antibiotic-associated pseudo-membranous colitis and diarrhea in humans. Clostridial toxins A and B (TcdA and TcdB) specifically bind to unknown glycoprotein(s) on the surface of epithelial cells in the host intestine, disrupting the intestinal barrier and ultimately leading to acute inflammation and diarrhea. The C-terminal receptor binding domain (RBD) of TcdA, which is responsible for the initial binding of the toxin to host glycoproteins, has been predicted to contain 7 potential oligosaccharide-binding sites. To study the specific roles and functions of these 7 putative lectin-like binding regions, a consensus sequence of TcdA RBD derived from different C. difficile strains deposited in the NCBI protein database and three truncated fragments corresponding to the N-terminal (residues 1-411), middle (residues 296-701), and C-terminal portions (residues 524-911) of the RBD (F1, F2 and F3, respectively) were designed and expressed in Escherichia coli. In this study, the recombinant RBD (rRBD) and its truncated fragments were purified, characterized biologically and found to have the following similar properties: (a) are capable of binding to the cell surface of both Vero and Caco-2 cells; (b) possess Toll-like receptor agonist-like adjuvant activities that can activate dendritic cell maturation and increase the secretion of pro-inflammatory cytokines; and (c) function as potent adjuvants in the intramuscular immunization route to enhance immune responses against weak immunogens. Although F1, F2 and F3 have similar repetitive amino acid sequences and putative oligosaccharide-binding domains, they do not possess the same biological and immunological properties: (i) TcdA rRBD and its fragments bind to the cell surface, but only TcdA rRBD and F3 internalize into Vero cells within 15 min; (ii) the fragments exhibit various levels of hemagglutinin (HA) activity, with the exception of the F1 fragment, which demonstrates no HA activity; and (iii) in the presence of alum, all fragments elicit various levels of anti-toxin A-neutralizing antibody responses, but those neutralizing antibodies elicited by F2 did not protect mice against a TcdA challenge. Because TcdA rRBD, F1 and F3 formulated with alum can elicit immune protective responses against the cytotoxicity of TcdA, they represent potential components of future candidate vaccines against C. difficile-associated diseases. PMID- 26271034 TI - Promoter Methylation Status Modulate the Expression of Tumor Suppressor (RbL2/p130) Gene in Breast Cancer. AB - BACKGROUND: Aberrant expression of tumor suppressor genes may correspond to the abnormal cell development and tumorigenesis. Rbl2/p130, a member of retinoblastoma family of proteins, has growth suppressive properties. Numerous studies reported de-regulation of Rbl2/p130 in various types of cancer as a consequence of a number of genetic alterations. However, role of epigenetic mechanisms like DNA methylation in Rbl2/p130 expression remains elusive. METHODS: In the current study, 76 breast cancer tumors along with normal tissues (n = 76), blood (n = 76) of respective individuals and control blood (n = 50) were analyzed. Rbl2/p130 expression was analyzed by quantitative real time PCR (syber green method). Promoter methylation status was studied through methylation specific PCR of bisulfite converted genomic DNA. Data was analyzed using various statistical tests. RESULTS: We report significantly reduced Rbl2/p130 expression (P = 0.001) in tumors tissues as compared to control samples. Similarly, Rbl2/p130 expression varies with age and disease stages (P = 0.022), which suggest its involvement in tumor progression. Aberrant promoter methylation (Deltameth) was found in almost all the diseased samples and that was significantly different (P<0.001) with control samples. Similarly, methylation status varies significantly with tumor progression stages (P = 0.022). Hyper methylation was observed at -1, +3, +15 and +75 of Rbl2/p130 promoter flanking around the TSS. Statistical analysis revealed that Rbl2/p130 expression negatively correlates to its promoter methylation (r = -0.412) in tumor tissues. Our results reflect an epigenetic regulation of Rbl2/p130 expression in breast cancer. This highlights the importance of Rbl2/p130 promoter methylation in breast cancer pathogenesis. PMID- 26271035 TI - The Impacts of Wind Speed Trends and 30-Year Variability in Relation to Hydroelectric Reservoir Inflows on Wind Power in the Pacific Northwest. AB - In hydroelectric dominated systems, the value and benefits of energy are higher during extended dry periods and lower during extended or extreme wet periods. By accounting for regional and temporal differences in the relationship between wind speed and reservoir inflow behavior during wind farm site selection, the benefits of energy diversification can be maximized. The goal of this work was to help maximize the value of wind power by quantifying the long-term (30-year) relationships between wind speed and streamflow behavior, using British Columbia (BC) and the Pacific Northwest (PNW) as a case study. Clean energy and self sufficiency policies in British BC make the benefits of increased generation during low streamflow periods particularly large. Wind density (WD) estimates from a height of 10m (North American Regional Reanalysis, NARR) were correlated with cumulative usable inflows (CUI) for BC (collected from BC Hydro) for 1979 2010. The strongest WD-CUI correlations were found along the US coast (r ~0.55), whereas generally weaker correlations were found in northern regions, with negative correlations (r ~ -0.25) along BC's North Coast. Furthermore, during the lowest inflow years, WD anomalies increased by up to 40% above average values for the North Coast. Seasonally, high flows during the spring freshet were coincident with widespread negative WD anomalies, with a similar but opposite pattern for low inflow winter months. These poorly or negatively correlated sites could have a moderating influence on climate related variability in provincial electricity supply, by producing greater than average generation in low inflow years and reduced generation in wet years. Wind speed and WD trends were also analyzed for all NARR grid locations, which showed statistically significant positive trends for most of the PNW and the largest increases along the Pacific Coast. PMID- 26271036 TI - Crizotinib-Induced Abnormal Signal Processing in the Retina. AB - Molecular target therapy for cancer is characterized by unique adverse effects that are not usually observed with cytotoxic chemotherapy. For example, the anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor crizotinib causes characteristic visual disturbances, whereas such effects are rare when another ALK-tyrosine kinase inhibitor, alectinib, is used. To elucidate the mechanism responsible for these visual disturbances, the responses to light exhibited by retinal ganglion cells treated with these agents were evaluated using a C57BL6 mouse ex vivo model. Both crizotinib and alectinib changed the firing rate of ON and OFF type retinal ganglion cells. However, the ratio of alectinib-affected cells (15.7%) was significantly lower than that of crizotinib-affected cells (38.6%). Furthermore, these drugs changed the response properties to light stimuli of retinal ganglion cells in some of the affected cells, i.e., OFF cells responded to both ON and OFF stimuli, etc. Finally, the expressions of ALK (a target receptor of both crizotinib and alectinib) and of MET and ROS1 (additional target receptors of crizotinib) were observed at the mRNA level in the retina. Our findings suggest that these drugs might target retinal ganglion cells and that the potency of the drug actions on the light responses of retinal ganglion cells might be responsible for the difference in the frequencies of visual disturbances observed between patients treated with crizotinib and those treated with alectinib. The present experimental system might be useful for screening new molecular target agents prior to their use in clinical trials. PMID- 26271037 TI - Evaluating the Learning Curve for Percutaneous Nephrolithotomy under Total Ultrasound Guidance. AB - OBJECTIVES: To investigate the learning curve of percutaneous nephrolithotomy under total ultrasound guidance. METHODS: One hundred and twenty consecutive PCNL operations under total ultrasound guidance performed by a novice surgeon in a tertiary referral center were studied. Operations were analyzed in cohorts of 15 to determine when a plateau was reached for the variables such as operation duration, ultrasound screening time, tract dilation time, stone-free rate and complication rate. Comparison was made with the results of a surgeon who had performed more than 1000 PCNLs. Fluoroscopy was not used at all during procedure. RESULTS: The mean operation time dropped from 82.5 min for the first 15 patients to a mean of 64.7 min for cases 46 through 60(P = 0.047). The ultrasound screening time was a peak of 6.4 min in the first 15 cases, whereas it dropped to a mean of 3.9 min for cases 46 through 60(P = 0.01). The tract dilation time dropped from 4.9 min for the first 15 patients to a mean of 3.8 min for cases 46 through 60(P = 0.036). The senior surgeon had a mean operating time, screening time and tract dilation time equivalent to those of the novice surgeon after 60 cases. There was no significant difference in stone free rate and complication rate. CONCLUSIONS: The competence of ultrasound guided PCNL is reached after 60 cases with good stone free rate and without major complications. PMID- 26271038 TI - Demonstration of the Coexistence of Duplicated LH Receptors in Teleosts, and Their Origin in Ancestral Actinopterygians. AB - Pituitary gonadotropins, FSH and LH, control gonad activity in vertebrates, via binding to their respective receptors, FSHR and LHR, members of GPCR superfamily. Until recently, it was accepted that gnathostomes possess a single FSHR and a single LHR, encoded by fshr and lhcgr genes. We reinvestigated this question, focusing on vertebrate species of key-phylogenetical positions. Genome analyses supported the presence of a single fshr and a single lhcgr in chondrichthyans, and in sarcopterygians including mammals, birds, amphibians and coelacanth. In contrast, we identified a single fshr but two lhgcr in basal teleosts, the eels. We further showed the coexistence of duplicated lhgcr in other actinopterygians, including a non-teleost, the gar, and other teleosts, e.g. Mexican tetra, platyfish, or tilapia. Phylogeny and synteny analyses supported the existence in actinopterygians of two lhgcr paralogs (lhgcr1/ lhgcr2), which do not result from the teleost-specific whole-genome duplication (3R), but likely from a local gene duplication that occurred early in the actinopterygian lineage. Due to gene losses, there was no impact of 3R on the number of gonadotropin receptors in extant teleosts. Additional gene losses during teleost radiation, led to a single lhgcr (lhgcr1 or lhgcr2) in some species, e.g. medaka and zebrafish. Sequence comparison highlighted divergences in the extracellular and intracellular domains of the duplicated lhgcr, suggesting differential properties such as ligand binding and activation mechanisms. Comparison of tissue distribution in the European eel, revealed that fshr and both lhgcr transcripts are expressed in the ovary and testis, but are differentially expressed in non-gonadal tissues such as brain or eye. Differences in structure-activity relationships and tissue expression may have contributed as selective drives in the conservation of the duplicated lhgcr. This study revises the evolutionary scenario and nomenclature of gonadotropin receptors, and opens new research avenues on the roles of duplicated LHR in actinopterygians. PMID- 26271039 TI - Insulin Protects Cardiac Myocytes from Doxorubicin Toxicity by Sp1-Mediated Transactivation of Survivin. AB - Insulin inhibits ischemia/reperfusion-induced myocardial apoptosis through the PI3K/Akt/mTOR pathway. Survivin is a key regulator of anti-apoptosis against doxorubicin-induced cardiotoxicity. Insulin increases survivin expression in cardiac myocytes to mediate cytoprotection. However, the mechanism by which survivin mediates the protective effect of insulin against doxorubicin-associated injury remains to be determined. In this study, we demonstrated that pretreatment of H9c2 cardiac myocytes with insulin resulted in a significant decrease in doxorubicin-induced apoptotic cell death by reducing cytochrome c release and caspase-3 activation. Doxorubicin-induced reduction of survivin mRNA and protein levels was also significantly perturbed by insulin pretreatment. Reducing survivin expression with survivin siRNA abrogated insulin-mediated inhibition of caspase-3 activation, suggesting that insulin signals to survivin inhibited caspase-3 activation. Interestingly, pretreatment of H9c2 cells with insulin or MG132, a proteasome inhibitor, inhibited doxorubicin-induced degradation of the transcription factor Sp1. ChIP assay showed that pretreatment with insulin inhibited doxorubicin-stimulated Sp1 dissociation from the survivin promoter. Finally using pharmacological inhibitors of the PI3K pathway, we showed that insulin-mediated activation of the PI3K/Akt/mTORC1 pathway prevented doxorubicin induced proteasome-mediated degradation of Sp1. Taken together, insulin pretreatment confers a protective effect against doxorubicin-induced cardiotoxicity by promoting Sp1-mediated transactivation of survivin to inhibit apoptosis. Our study is the first to define a role for survivin in cellular protection by insulin against doxorubicin-associated injury and show that Sp1 is a critical factor in the transcriptional regulation of survivin. PMID- 26271041 TI - TAT-Mediated Acidic Fibroblast Growth Factor Delivery to the Dermis Improves Wound Healing of Deep Skin Tissue in Rat. AB - BACKGROUND: The definition of deep tissue injury was derived from multiple clinical cases as "A purple or maroon localized area of discolored intact skin or blood-filled blister due to damage of underlying soft tissue from pressure and/or shear". Acidic fibroblast growth factor (aFGF) significantly improves wound healing under diabetic conditions. However, to date, the therapeutic application of aFGF has been limited, due to its low delivery efficiency and short half-life. METHODOLOGY/PRINCIPAL FINDINGS: Using an animal model of magnet-induced pressure ulcers, transactivator of transcription protein (TAT)-aFGF was evaluated for transdermal delivery and wound healing. Immunohistochemistry and Western blotting were also performed to determine the expression of transforming growth factor (TGF)-beta1, alpha-smooth muscle actin (alpha-SMA), CD68, proliferating cell nuclear antigen (PCNA) and TGF-beta-receptor II (TGF- betaRII) in cultured human dermal fibroblasts. We found that that mice treated with TAT-aFGF had higher accumulation of aFGF in both dermis and subcutaneous tissues compared with mice treated with aFGF alone. In the remodeling phase, TAT-aFGF treatment decreased the expression of alpha-SMA to normal levels, thereby facilitating normal wound healing processes and abrogating hypertrophic scarring. In human dermal fibroblasts, TAT-aFGF reversed the suppressive effect of TNF-alpha on alpha-SMA expression and restored TGF-betaRII and TGF-beta1 expression. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that TAT-aFGF has a favorable therapeutic effect on the healing of subcutaneous deep tissue injury. PMID- 26271043 TI - ExScalibur: A High-Performance Cloud-Enabled Suite for Whole Exome Germline and Somatic Mutation Identification. AB - Whole exome sequencing has facilitated the discovery of causal genetic variants associated with human diseases at deep coverage and low cost. In particular, the detection of somatic mutations from tumor/normal pairs has provided insights into the cancer genome. Although there is an abundance of publicly-available software for the detection of germline and somatic variants, concordance is generally limited among variant callers and alignment algorithms. Successful integration of variants detected by multiple methods requires in-depth knowledge of the software, access to high-performance computing resources, and advanced programming techniques. We present ExScalibur, a set of fully automated, highly scalable and modulated pipelines for whole exome data analysis. The suite integrates multiple alignment and variant calling algorithms for the accurate detection of germline and somatic mutations with close to 99% sensitivity and specificity. ExScalibur implements streamlined execution of analytical modules, real-time monitoring of pipeline progress, robust handling of errors and intuitive documentation that allows for increased reproducibility and sharing of results and workflows. It runs on local computers, high-performance computing clusters and cloud environments. In addition, we provide a data analysis report utility to facilitate visualization of the results that offers interactive exploration of quality control files, read alignment and variant calls, assisting downstream customization of potential disease-causing mutations. ExScalibur is open-source and is also available as a public image on Amazon cloud. PMID- 26271042 TI - Nut Production in Bertholletia excelsa across a Logged Forest Mosaic: Implications for Multiple Forest Use. AB - Although many examples of multiple-use forest management may be found in tropical smallholder systems, few studies provide empirical support for the integration of selective timber harvesting with non-timber forest product (NTFP) extraction. Brazil nut (Bertholletia excelsa, Lecythidaceae) is one of the world's most economically-important NTFP species extracted almost entirely from natural forests across the Amazon Basin. An obligate out-crosser, Brazil nut flowers are pollinated by large-bodied bees, a process resulting in a hard round fruit that takes up to 14 months to mature. As many smallholders turn to the financial security provided by timber, Brazil nut fruits are increasingly being harvested in logged forests. We tested the influence of tree and stand-level covariates (distance to nearest cut stump and local logging intensity) on total nut production at the individual tree level in five recently logged Brazil nut concessions covering about 4000 ha of forest in Madre de Dios, Peru. Our field team accompanied Brazil nut harvesters during the traditional harvest period (January-April 2012 and January-April 2013) in order to collect data on fruit production. Three hundred and ninety-nine (approximately 80%) of the 499 trees included in this study were at least 100 m from the nearest cut stump, suggesting that concessionaires avoid logging near adult Brazil nut trees. Yet even for those trees on the edge of logging gaps, distance to nearest cut stump and local logging intensity did not have a statistically significant influence on Brazil nut production at the applied logging intensities (typically 1-2 timber trees removed per ha). In one concession where at least 4 trees ha-1 were removed, however, the logging intensity covariate resulted in a marginally significant (0.09) P value, highlighting a potential risk for a drop in nut production at higher intensities. While we do not suggest that logging activities should be completely avoided in Brazil nut rich forests, when a buffer zone cannot be observed, low logging intensities should be implemented. The sustainability of this integrated management system will ultimately depend on a complex series of socioeconomic and ecological interactions. Yet we submit that our study provides an important initial step in understanding the compatibility of timber harvesting with a high value NTFP, potentially allowing for diversification of forest use strategies in Amazonian Peru. PMID- 26271040 TI - Nanoformulations of Rilpivirine for Topical Pericoital and Systemic Coitus Independent Administration Efficiently Prevent HIV Transmission. AB - Vaginal HIV transmission accounts for the majority of new infections worldwide. Currently, multiple efforts to prevent HIV transmission are based on pre-exposure prophylaxis with various antiretroviral drugs. Here, we describe two novel nanoformulations of the reverse transcriptase inhibitor rilpivirine for pericoital and coitus-independent HIV prevention. Topically applied rilpivirine, encapsulated in PLGA nanoparticles, was delivered in a thermosensitive gel, which becomes solid at body temperature. PLGA nanoparticles with encapsulated rilpivirine coated the reproductive tract and offered significant protection to BLT humanized mice from a vaginal high-dose HIV-1 challenge. A different nanosuspension of crystalline rilpivirine (RPV LA), administered intramuscularly, protected BLT mice from a single vaginal high-dose HIV-1 challenge one week after drug administration. Using transmitted/founder viruses, which were previously shown to establish de novo infection in humans, we demonstrated that RPV LA offers significant protection from two consecutive high-dose HIV-1 challenges one and four weeks after drug administration. In this experiment, we also showed that, in certain cases, even in the presence of drug, HIV infection could occur without overt or detectable systemic replication until levels of drug were reduced. We also showed that infection in the presence of drug can result in acquisition of multiple viruses after subsequent exposures. These observations have important implications for the implementation of long-acting antiretroviral formulations for HIV prevention. They provide first evidence that occult infections can occur, despite the presence of sustained levels of antiretroviral drugs. Together, our results demonstrate that topically- or systemically administered rilpivirine offers significant coitus-dependent or coitus independent protection from HIV infection. PMID- 26271045 TI - Rapid Characterization of Microalgae and Microalgae Mixtures Using Matrix Assisted Laser Desorption Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF MS). AB - Current molecular methods to characterize microalgae are time-intensive and expensive. Matrix Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) may represent a rapid and economical alternative approach. The objectives of this study were to determine whether MALDI-TOF MS can be used to: 1) differentiate microalgae at the species and strain levels and 2) characterize simple microalgal mixtures. A common protein extraction sample preparation method was used to facilitate rapid mass spectrometry-based analysis of 31 microalgae. Each yielded spectra containing between 6 and 56 peaks in the m/z 2,000 to 20,000 range. The taxonomic resolution of this approach appeared higher than that of 18S rDNA sequence analysis. For example, two strains of Scenedesmus acutus differed only by two 18S rDNA nucleotides, but yielded distinct MALDI-TOF mass spectra. Mixtures of two and three microalgae yielded relatively complex spectra that contained peaks associated with members of each mixture. Interestingly, though, mixture-specific peaks were observed at m/z 11,048 and 11,230. Our results suggest that MALDI-TOF MS affords rapid characterization of individual microalgae and simple microalgal mixtures. PMID- 26271047 TI - Is frailty in the elderly linked to inflammation? PMID- 26271046 TI - Role of Site-Specific N-Glycans Expressed on GluA2 in the Regulation of Cell Surface Expression of AMPA-Type Glutamate Receptors. AB - The AMPA-type glutamate receptor (AMPAR), which is a tetrameric complex composed of four subunits (GluA1-4) with several combinations, mediates the majority of rapid excitatory synaptic transmissions in the nervous system. Cell surface expression levels of AMPAR modulate synaptic plasticity, which is considered one of the molecular bases for learning and memory formation. To date, a unique trisaccharide (HSO3-3GlcAbeta1-3Galbeta1-4GlcNAc), human natural killer-1 (HNK-1) carbohydrate, was found expressed specifically on N-linked glycans of GluA2 and regulated the cell surface expression of AMPAR and the spine maturation process. However, evidence that the HNK-1 epitope on N-glycans of GluA2 directly affects these phenomena is lacking. Moreover, it is thought that other N-glycans on GluA2 also have potential roles in the regulation of AMPAR functions. In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413) within GluA2, we demonstrated that the mutant lacking the N glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER) in HEK293 cells. Cell surface expression of GluA1, which is a major subunit of AMPAR in neurons, was also suppressed by co expression of the GluA2 N370S mutant. The N370S mutant and wild-type GluA2 were co-immunoprecipitated with GluA1, suggesting that N370S was properly associated with GluA1. Moreover, we found that N413 was the main potential site of the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2. The HNK-1 epitope on N-glycan at the N413 of GluA2 was also involved in the cell surface expression of GluA1. Thus, our data suggested that site-specific N-glycans on GluA2 regulate the intracellular trafficking and cell surface expression of AMPAR. PMID- 26271044 TI - Survival and Effectiveness of Tumour Necrosis Factor-alpha Inhibitors in the Treatment of Plaque Psoriasis under Daily Life Conditions: Report from the Psoriasis Registry Austria. AB - This retrospective multicentre analysis from the Psoriasis Registry Austria (PsoRA) was conducted to determine drug effectiveness and survival of anti-tumour necrosis factor alpha (anti-TNF-alpha) agents in patients with moderate-to-severe chronic plaque psoriasis over a 9-year period. Data on 1,019 treatment cycles with adalimumab (n = 460), etanercept (n = 501), and/or infliximab (n = 58) administered to 827 patients (272 women, 555 men) were available for analysis. Compared with etanercept, adalimumab and infliximab showed superior short-term effectiveness. Intention-to-treat-calculated median drug survivals for adalimumab (1,264 days) and etanercept (1,438 days) were similar to each other (p = 0.74), but significantly superior to that of infliximab (477 days) (p = 7.0e-07 vs. adalimumab and p=2.2e-07 vs. etanercept, respectively). Their drug survival rates at 36 months were 51.6%, 56.0%, and 22.6%, respectively. Survival rates correlated significantly with effectiveness for adalimumab and etanercept, but not for infliximab. PMID- 26271049 TI - Intellectual and physical activities, but not social activities, are associated with better global cognition: a multi-site evaluation of the cognition and lifestyle activity study for seniors in Asia (CLASSA). AB - BACKGROUND: population ageing will lead to a leap in the dementia population in Asia. However, information about potentials for low-cost and low-risk interventions is limited. OBJECTIVES: to study the associations between lifestyle activities and global cognition from the Cognitive and Lifestyle Activity Study for Seniors in Asia (CLASSA). DESIGN: a cross-sectional study. METHODOLOGY: we studied the association between global cognition and lifestyle activity participation in community living older adults (60 years or over) across nine sites in East Asia. A standardised lifestyle activity questionnaire exploring activities from four categories (intellectual, physical, social and recreational) was used to measure the pattern. Global cognition was categorised by locally validated versions of Mini-mental state examination (MMSE) or Montreal Cognitive Assessment (MoCA) (good cognition, GC-scored at the top 25% among participants with no significant cognitive deficit (SCD); normal cognition, NC-middle 50% among participants with no SCD; mild cognitive deficit, MCD-lowest 25% among participants with no SCD; SCD-below local cut-offs for dementia). RESULTS: two thousand four hundred and four (1,009 men; 1,395 women) participants were recruited. The mean age was 71.0 (7.2) years. A higher variety of intellectual and physical activities were associated with GC; more social activities were associated with higher risks of having impaired cognition (multinomial logistic regression). The same association was found in participants with no SCD and had regular activities for over 10 years (n = 574). CONCLUSION: intellectual activity and physical exercise were associated with better cognitive states in Asian older adults. Community-based intervention may take considerations into specific types of activities to optimise cognition. PMID- 26271048 TI - Falls and fractures 2 years after acute stroke: the North Dublin Population Stroke Study. AB - BACKGROUND: Stroke patients are at increased risk of falls and fractures. The aim of this study was to determine the rate, predictors and consequences of falls within 2 years after stroke in a prospective population-based study in North Dublin, Ireland. DESIGN: Prospective population-based cohort study. SUBJECTS: 567 adults aged >18 years from the North Dublin Population Stroke Study. METHODS: Participants were enrolled from an Irish urban population of 294,592 individuals, according to recommended criteria. Patients were followed for 2 years. Outcome measures included death, modified Rankin Scale (mRS), fall and fracture rate. RESULTS: At 2 years, 23.5% (124/522) had fallen at least once since their stroke, 14.2% (74/522) had 2 or more falls and 5.4% (28/522) had a fracture. Of 332 survivors at 2 years, 107 (32.2%) had fallen, of whom 60.7% (65/107) had 2 or more falls and 23.4% (25/107) had fractured. In a multivariable model controlling for age and gender, independent risk factors for falling within the first 2 years of stroke included use of alpha-blocker medications for treatment of hypertension (P = 0.02). When mobility measured at Day 90 was included in the model, patients who were mobility impaired (mRS 2-3) were at the highest risk of falling within 2 years of stroke [odds ratio (OR) 2.30, P = 0.003] and those functionally dependent (mRS 4-5) displayed intermediate risk (OR 2.02, P = 0.03) when compared with independently mobile patients. CONCLUSION: Greater attention to falls risk, fall prevention strategies and bone health in the stroke population are required. PMID- 26271051 TI - Reply: To PMID 25825070. PMID- 26271050 TI - Efficacy of Ciprofloxacin for Treatment of Cholera Associated with Diminished Susceptibility to Ciprofloxacin to Vibrio cholerae O1. AB - OBJECTIVE: We identified a poor clinical response to treatment of cholera with a single 1 g dose of ciprofloxacin, a standard treatment for cholera. METHODS: To determine reasons for the poor response and better therapeutic approaches we examined the minimal inhibitor concentration (MIC, n = 275) and disc-diffusion zone sizes (n = 205) for ciprofloxacin and nalidixic acid of V. cholerae O1 strains isolated in Bangladesh from 1994 to 2012, and reexamined data from 161 patients infected with Vibrio cholerae O1 recruited in four clinical trials who received single- or multiple-dose ciprofloxacin for treatment of cholera and compared their clinical response to the V. cholerae O1 susceptibility. RESULTS: Although all 275 isolates of V. cholerae O1 remained susceptible to ciprofloxacin using standard MIC and disc-diffusion thresholds, the MIC90 to ciprofloxacin increased from 0.010 in 1994 to 0.475 MUgm/ml in 2012. Isolates became frankly resistant to nalidixic with the MIC90 increasing from 21 MUgm/ml in 1994 to >256 MUgm/ml and 166 of 205 isolates from 1994 to 2005 being frankly resistant using disc-diffusion testing. Isolates resistant to nalidixic acid by disc-diffusion testing had a median ciprofloxacin MIC of 0.190 MUgm/ml (10th-90th centiles 0.022 to 0.380); nalidixic acid-susceptible isolates had a median ciprofloxacin MIC of 0.002 (0.002 to 0.012).The rate of clinical success with single-dose ciprofloxacin treatment for nalidixic acid-susceptible strains was 94% (61 of 65 patients) and bacteriologic success 97% (63/65) compared to 18% (12/67) and 8% (5/67) respectively with nalidixic acid-resistant strains (P<0.001 for both comparisons). Multiple-dose treatment with ciprofloxacin had 86% and 100% clinical and bacteriologic success rates respectively in patients infected with nalidixic acid-susceptible strains of V. cholerae O1 compared to clinical success 67% and bacteriologic success 60% with nalidixic acid-resistant strains. CONCLUSIONS: Single-dose ciprofloxacin is not effective for treating cholera caused by V. cholerae O1 with diminished susceptibility to ciprofloxacin, and nalidixic acid disc-diffusion testing effectively screens for such isolates. PMID- 26271053 TI - Multispectral hybrid Cerenkov luminescence tomography based on the finite element SPn method. AB - Cerenkov luminescence tomography (CLT) is a promising tool that enables three dimensional noninvasive in vivo detection of radiopharmaceuticals. Conventionally, multispectral information and diffusion theory were introduced to achieve whole-body tomographic reconstruction. However, the diffusion theory inevitably causes systematic error in blue bands of the electromagnetic spectrum due to high-tissue absorption, and CL has a blue-weighted broad spectrum. Therefore, it is challenging to improve the accuracy of CLT. The performance of the n -order simplified spherical harmonics approximation (SPn) in different spectra is evaluated, and a multispectral hybrid CLT based on the combination of different SPn models is proposed to handle the Cerenkov photon transport problem in complex media. The in vivo xenograft experiment shows that this approach can effectively improve the quality and accuracy of the reconstructed light source. We believe that the new reconstruction method will advance the development of CLT for more in vivo imaging applications PMID- 26271054 TI - Increasing depth penetration in biological tissue imaging using 808-nm excited Nd3+/Yb3+/Er3+-doped upconverting nanoparticles. AB - Ytterbium (Yb 3+ )-sensitized upconverting nanoparticles (UCNPs) are excited at 975 nm causing relatively high absorption in tissue. A new type of UCNPs with neodymium (Nd 3+ ) and Yb 3+ codoping is excitable at a 808-nm wavelength. At this wavelength, the tissue absorption is lower. Here we quantify, both experimentally and theoretically, to what extent Nd 3+ -doped UCNPs will provide an increased signal at larger depths in tissue compared to conventional 975-nm excited UCNPs. PMID- 26271052 TI - Hybrid imaging of fluorescently labeled cancer drugs and label-free four-wave mixing microscopy of cancer cells and tissues. AB - Fluorescent labels are well suited as tracers for cancer drug monitoring. Identifying cellular target regions of these drugs with a high resolution is important to assess the working principle of a drug. We investigate the applications of label-free nonresonant four-wave mixing (NR-FWM) microscopy in biological imaging in combination with fluorescence imaging of fluorescently labeled cancer drugs. Results from human A431 tumor cells with stained nuclei and incubated with IRdye 800CW labeled cancer drug cetuximab targeting epidermal growth factor receptor at the cell membrane show that NR-FWM is well suited for cellular imaging. A comparison of vibrationally nonresonant FWM imaging with vibrational resonant coherent anti-Stokes Raman scattering signals revealed nearly identical qualitative information in cellular imaging. NR-FWM is also suitable for tumor tissue imaging in combination with fluorescence imaging of IRdye 800CW labeled, human epidermal growth factor 2 targeting cancer drug pertuzumab and provides additional information over transmission microscopy. PMID- 26271055 TI - Static laser speckle contrast analysis for noninvasive burn diagnosis using a camera-phone imager. AB - Laser speckle contrast analysis (LASCA) is an established optical technique for accurate widefield visualization of relative blood perfusion when no or minimal scattering from static tissue elements is present, as demonstrated, for example, in LASCA imaging of the exposed cortex. However, when LASCA is applied to diagnosis of burn wounds, light is backscattered from both moving blood and static burn scatterers, and thus the spatial speckle contrast includes both perfusion and nonperfusion components and cannot be straightforwardly associated to blood flow. We extract from speckle contrast images of burn wounds the nonperfusion (static) component and discover that it conveys useful information on the ratio of static-to-dynamic scattering composition of the wound, enabling identification of burns of different depth in a porcine model in vivo within the first 48 h postburn. Our findings suggest that relative changes in the static-to dynamic scattering composition of burns can dominate relative changes in blood flow for burns of different severity. Unlike conventional LASCA systems that employ scientific or industrial-grade cameras, our LASCA system is realized here using a camera phone, showing the potential to enable LASCA-based burn diagnosis with a simple imager. PMID- 26271056 TI - Mechanical contrast in spectroscopic magnetomotive optical coherence elastography. AB - The viscoelastic properties of tissues are altered during pathogenesis of numerous diseases and can therefore be a useful indicator of disease status and progression. Several elastography studies have utilized the mechanical frequency response and the resonance frequencies of tissue samples to characterize their mechanical properties. However, using the resonance frequency as a source of mechanical contrast in heterogeneous samples is complicated because it not only depends on the viscoelastic properties but also on the geometry and boundary conditions. In an elastography technique called magnetomotive optical coherence elastography (MM-OCE), the controlled movement of magnetic nanoparticles (MNPs) within the sample is used to obtain the mechanical properties. Previous demonstrations of MM-OCE have typically used point measurements in elastically homogeneous samples assuming a uniform concentration of MNPs. In this study, we evaluate the feasibility of generating MM-OCE elastograms in heterogeneous samples based on a spectroscopic approach which involves measuring the magnetomotive response at different excitation frequencies. Biological tissues and tissue-mimicking phantoms with two elastically distinct regions placed in side-by-side and bilayer configurations were used for the experiments, and finite element method simulations were used to validate the experimental results. PMID- 26271058 TI - Why Optimal Medical Therapy Should Be a Universal Standard of Care. PMID- 26271057 TI - Comprehensive Cardiovascular Risk Factor Control Improves Survival: The BARI 2D Trial. AB - BACKGROUND: It is unclear whether achieving multiple risk factor (RF) goals through protocol-guided intensive medical therapy is feasible or improves outcomes in type 2 diabetes mellitus. OBJECTIVES: This study sought to quantify the relationship between achieved RF goals in the BARI 2D (Bypass Angioplasty Investigation Revascularization 2 Diabetes) trial and cardiovascular events/survival. METHODS: We performed a nonrandomized analysis of survival/cardiovascular events and control of 6 RFs (no smoking, non-high-density lipoprotein cholesterol <130 mg/dl, triglycerides <150 mg/dl, blood pressure [systolic <130 mm Hg; diastolic <80 mm Hg], glycosylated hemoglobin <7%) in BARI 2D. Cox models with time-varying number of RFs in control were adjusted for baseline number of RFs in control, clinical characteristics, and trial randomization assignments. RESULTS: In 2,265 patients (mean age 62 years, 29% women) followed up for 5 years, the mean +/- SD number of RFs in control improved from 3.5 +/- 1.4 at baseline to 4.2 +/- 1.3 at 5 years (p < 0.0001). The number of RFs in control during the trial was strongly related to death (global p = 0.0010) and the composite of death, myocardial infarction, and stroke (global p = 0.0035) in fully adjusted models. Participants with 0 to 2 RFs in control during follow-up had a 2-fold higher risk of death (hazard ratio: 2.0; 95% confidence interval: 1.3 to 3.3; p = 0.0031) and a 1.7-fold higher risk of the composite endpoint (hazard ratio: 1.7; 95% confidence interval: 1.2 to 2.5; p = 0.0043), compared with those with 6 RFs in control. CONCLUSIONS: Simultaneous control of multiple RFs through protocol-guided intensive medical therapy is feasible and relates to cardiovascular morbidity and mortality in patients with coronary disease and type 2 diabetes mellitus. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI 2D]; NCT00006305). PMID- 26271059 TI - Apixaban Plus Mono Versus Dual Antiplatelet Therapy in Acute Coronary Syndromes: Insights From the APPRAISE-2 Trial. AB - BACKGROUND: Bleeding limits anticoagulant treatment in patients with acute coronary syndromes (ACS). OBJECTIVES: We investigated whether background concomitant antiplatelet therapy influences the effects of apixaban after ACS. METHODS: This study examined high-risk ACS patients who were treated with aspirin or aspirin plus clopidogrel and who were randomized to apixaban 5 mg twice daily or placebo. In a post-hoc analysis, we assessed whether the effect of apixaban on efficacy and safety outcomes varied by the concomitant antiplatelet regimen by using simple Cox modeling and marginal structural models with propensity scores and antiplatelet therapy as a time-dependent covariate. RESULTS: At baseline, of 7,364 patients, 16.3% (n = 1,202) were on aspirin alone, and 79.0% (n = 5,814) were on aspirin plus clopidogrel. A total of 19.2% (n = 1,415) switched antiplatelet therapy during follow-up. No differential effect of apixaban versus placebo was observed for the composite endpoint of cardiovascular death, myocardial infarction, and ischemic stroke in patients taking aspirin (12.21 per 100 patient-years vs. 13.21 per 100 patient-years; adjusted hazard ratio [HR]: 0.91; 95% confidence interval [CI]: 0.62 to 1.32) or aspirin plus clopidogrel (13.22 vs. 14.24; adjusted HR: 0.95; 95% CI: 0.78 to 1.14; p(interaction)= 0.84). Compared with placebo, apixaban increased Thrombolysis In Myocardial Infarction major bleeding in patients taking aspirin (1.48 vs. 0.25; adjusted HR: 6.62; 95% CI: 0.75 to 51.73) and in patients taking aspirin plus clopidogrel (2.58 vs. 1.02; adjusted HR: 2.44; 95% CI: 1.34 to 4.45; p(interaction)= 0.41). Similar results were obtained with marginal structural models and in patients treated with and without percutaneous coronary intervention. CONCLUSIONS: Post-ACS treatment with apixaban versus placebo showed no efficacy, but it increased bleeding regardless of concomitant therapy with aspirin alone or aspirin plus clopidogrel. (Apixaban for Prevention of Acute Ischemic Events 2 [APPRAISE-2]; NCT00831441). PMID- 26271060 TI - The Challenge of Getting it Just Right: Optimizing Long-Term Antithrombotic Therapy After Acute Coronary Syndrome. PMID- 26271061 TI - 1-Year Outcomes After Transcatheter Aortic Valve Replacement With Balloon Expandable Versus Self-Expandable Valves: Results From the CHOICE Randomized Clinical Trial. AB - BACKGROUND: The use of a balloon-expandable transcatheter heart valve previously resulted in a greater rate of device success compared with a self-expandable transcatheter heart valve. OBJECTIVES: The aim of this study was to evaluate clinical and echocardiographic outcome data at longer term follow-up. METHODS: The investigator-initiated trial randomized 241 high-risk patients with symptomatic severe aortic stenosis and anatomy suitable for treatment with both balloon- and self-expandable transcatheter heart valves to transfemoral transcatheter aortic valve replacement with either device. Patients were followed up for 1 year, with assessment of clinical outcomes and echocardiographic evaluation of valve function. RESULTS: At 1 year, the rates of death of any cause (17.4% vs. 12.8%; relative risk [RR]: 1.35; 95% confidence interval [CI]: 0.73 to 2.50; p = 0.37) and of cardiovascular causes (12.4% vs. 9.4%; RR: 1.32; 95% CI: 0.63 to 2.75; p = 0.54) were not statistically significantly different in the balloon- and self-expandable groups, respectively. The frequencies of all strokes (9.1% vs. 3.4%; RR: 2.66; 95% CI: 0.87 to 8.12; p = 0.11) and repeat hospitalization for heart failure (7.4% vs. 12.8%; RR: 0.58; 95% CI: 0.26 to 1.27; p = 0.19) did not statistically significantly differ between the 2 groups. Elevated transvalvular gradients during follow-up were observed in 4 patients in the balloon-expandable group (3.4% vs. 0%; p = 0.12); all were resolved with anticoagulant therapy, suggesting a thrombotic etiology. More than mild paravalvular regurgitation was more frequent in the self-expandable group (1.1% vs. 12.1%; p = 0.005). CONCLUSIONS: Despite the higher device success rate with the balloon-expandable valve, 1-year follow-up of patients in CHOICE (Randomized Comparison of Transcatheter Heart Valves in High Risk Patients With Severe Aortic Stenosis: Medtronic CoreValve Versus Edwards SAPIEN XT Trial), with limited statistical power, revealed clinical outcomes after transfemoral transcatheter aortic valve replacement with both balloon- and self-expandable prostheses that were not statistically significantly different. (A Comparison of Transcatheter Heart Valves in High Risk Patients With Severe Aortic Stenosis: The CHOICE Trial; NCT01645202). PMID- 26271062 TI - The Choice Will Be Tailored TAVR Therapy: "The Talent Is in the Choices". PMID- 26271063 TI - 1-Year Outcomes After Transfemoral Transcatheter or Surgical Aortic Valve Replacement: Results From the Italian OBSERVANT Study. AB - BACKGROUND: There is a paucity of prospective and controlled data on the comparative effectiveness of transcatheter aortic valve replacement (TAVR) versus surgical aortic valve replacement (SAVR) in a real-world setting. OBJECTIVES: This analysis aims to describe 1-year clinical outcomes of a large series of propensity-matched patients who underwent SAVR and transfemoral TAVR. METHODS: The OBSERVANT (Observational Study of Effectiveness of SAVR-TAVI Procedures for Severe Aortic Stenosis Treatment) trial is an observational prospective multicenter cohort study that enrolled patients with aortic stenosis (AS) who underwent SAVR or TAVR. The propensity score method was applied to select 2 groups with similar baseline characteristics. All outcomes were adjudicated through a linkage with administrative databases. The primary endpoints of this analysis were death from any cause and major adverse cardiac and cerebrovascular events (MACCE) at 1 year. RESULTS: The unadjusted enrolled population (N = 7,618) included 5,707 SAVR patients and 1,911 TAVR patients. The matched population had a total of 1,300 patients (650 per group). The propensity score method generated a low-intermediate risk population (mean logistic EuroSCORE 1: 10.2 +/- 9.2% vs. 9.5 +/- 7.1%, SAVR vs. transfemoral TAVR; p = 0.104). At 1 year, the rate of death from any cause was 13.6% in the surgical group and 13.8% in the transcatheter group (hazard ratio [HR]: 0.99; 95% confidence interval [CI]: 0.72 to 1.35; p = 0.936). Similarly, there were no significant differences in the rates of MACCE, which were 17.6% in the surgical group and 18.2% in the transcatheter group (HR: 1.03; 95% CI: 0.78 to 1.36; p = 0.831). The cumulative incidence of cerebrovascular events, and rehospitalization due to cardiac reasons and acute heart failure was similar in both groups at 1 year. CONCLUSIONS: The results suggest that SAVR and transfemoral TAVR have comparable mortality, MACCE, and rates of rehospitalization due to cardiac reasons at 1 year. These data need to be confirmed in longer term and dedicated ongoing randomized trials. PMID- 26271064 TI - Aortic Stenosis: Valve Replacement or Valve Implantation? PMID- 26271066 TI - Building a Unified Mechanistic Insight Into the Bimodal Pattern of Edema in Reperfused Acute Myocardial Infarctions: Observations, Interpretations, and Outlook. PMID- 26271065 TI - Pathophysiology Underlying the Bimodal Edema Phenomenon After Myocardial Ischemia/Reperfusion. AB - BACKGROUND: Post-ischemia/reperfusion (I/R) myocardial edema was recently shown to follow a consistent bimodal pattern: an initial wave of edema appears on reperfusion and dissipates at 24 h, followed by a deferred wave that initiates days after infarction, peaking at 1 week. OBJECTIVES: This study examined the pathophysiology underlying this post-I/R bimodal edematous reaction. METHODS: Forty instrumented pigs were assigned to different myocardial infarction protocols. Edematous reaction was evaluated by water content quantification, serial cardiac magnetic resonance T2-mapping, and histology/immunohistochemistry. The association of reperfusion with the initial wave of edema was evaluated in pigs undergoing 40-min/80-min I/R and compared with pigs undergoing 120-min ischemia with no reperfusion. The role of tissue healing in the deferred wave of edema was evaluated by comparing pigs undergoing standard 40-min/7-day I/R with animals subjected to infarction without reperfusion (chronic 7-day coronary occlusion) or receiving post-I/R high-dose steroid therapy. RESULTS: Characterization of post-I/R tissue changes revealed maximal interstitial edema early on reperfusion in the ischemic myocardium, with maximal content of neutrophils, macrophages, and collagen at 24 h, day 4, and day 7 post-I/R, respectively. Reperfused pigs had significantly higher myocardial water content at 120 min and T2 relaxation times on 120 min cardiac magnetic resonance than nonreperfused animals. Permanent coronary occlusion or high-dose steroid therapy significantly reduced myocardial water content on day 7 post-infarction. The dynamics of T2 relaxation times during the first post-infarction week were altered significantly in nonreperfused pigs compared with pigs undergoing regular I/R. CONCLUSIONS: The 2 waves of the post-I/R edematous reaction are related to different pathophysiological phenomena. Although the first wave is secondary to reperfusion, the second wave occurs mainly because of tissue healing processes. PMID- 26271068 TI - Orthostatic Hypotension: Epidemiology, Prognosis, and Treatment. AB - Orthostatic hypotension (OH) is a common cardiovascular disorder, with or without signs of underlying neurodegenerative disease. OH is diagnosed on the basis of an orthostatic challenge and implies a persistent systolic/diastolic blood pressure decrease of at least 20/10 mm Hg upon standing. Its prevalence is age dependent, ranging from 5% in patients <50 years of age to 30% in those >70 years of age. OH may complicate treatment of hypertension, heart failure, and coronary heart disease; cause disabling symptoms, faints, and traumatic injuries; and substantially reduce quality of life. Despite being largely asymptomatic or with minimal symptoms, the presence of OH independently increases mortality and the incidence of myocardial infarction, stroke, heart failure, and atrial fibrillation. In this review, we outline the etiology and prevalence of OH in the general population, summarize its relationship with morbidity and mortality, propose a diagnostic and therapeutic algorithm, and delineate current challenges and future perspectives. PMID- 26271069 TI - Medicare and Medicaid: An Anniversary to Remember. PMID- 26271067 TI - Duration of Dual Antiplatelet Therapy After Coronary Stenting: A Review of the Evidence. AB - The duration of dual antiplatelet therapy (DAPT) after coronary stenting has been evaluated in randomized studies with apparently conflicting results. Although longer exposure associates with more bleeding complications, late stent thrombosis (ST) and myocardial infarction are reduced. In addition, as new drug eluting stents carry a lower risk of ST compared with the first-generation drug eluting stents and possibly even bare-metal stents, a shift toward better protection from ST may have an effect on the duration and intensity of DAPT. Whether the duration of DAPT should be shorter or longer than the currently recommended 6 to 12 months is analyzed in this review, drawing on lessons from the most recent studies. PMID- 26271070 TI - The Role of Nurses in Promoting Cardiovascular Health Worldwide: The Global Cardiovascular Nursing Leadership Forum. PMID- 26271071 TI - Inpatient Cardiology Consultation Service: Transitioning Fellows-in-Training to Independent Cardiovascular Consultants. PMID- 26271072 TI - Incidence of Metabolic Risk Factors Among Healthy Obese Adults: 20-Year Follow Up. PMID- 26271073 TI - The Value of Cardiac Magnetic Resonance Imaging in Evaluation of Pediatric Patients for Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy. PMID- 26271074 TI - Reply: The Value of Cardiac Magnetic Resonance Imaging in Evaluation of Pediatric Patients for Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy. PMID- 26271075 TI - Management of Patients With Prosthetic Valve Thrombosis After Failed Thrombolytic Therapy. PMID- 26271077 TI - Incidental radiographic finding of the concealed art of susuk. AB - Susuk, or charm needles, are small, metallic needles inserted under the skin, considered to enhance beauty, health and luck. This hidden secret of inserting susuk is a traditional superstitious ritual, widely practiced among women of Southeast Asia. Here, we present an interesting case of incidental radiographic finding of the concealed art of susuk, which was exposed on a panoramic radiograph taken on a routine basis as a part of diagnostic work up at our centre. An orthopantomogram revealed bilateral metallic foreign bodies in the maxillo-facial region. Anamnestic data affirmed the practice of the body art of susuk. The charm needles were present in the orofacial region without the patient experiencing any pathological signs or symptoms. PMID- 26271078 TI - Destabilizing DNA during Rejoining Enhances Fidelity of Repair. AB - A new study shows that during repair of DNA, the effect of a single-strand annealing protein is to destabilize DNA duplex formation so that annealing only occurs between perfectly matched strands; the protein then clamps the strands together for repair. Read the Research Article. PMID- 26271079 TI - Developmental Status: Impact of Short-Term Ischemia on Follicular Survival of Whole Ovarian Transplantation in a Rabbit Model. AB - Ischemia is the first mechanism that provokes the loss of follicles in ovarian grafts over the long term. In whole ovarian transplantation, it remains unknown, however, how changes in follicular development are influenced by short-term ischemia. Fresh whole ovarian orthotopic auto-transplantation was performed in rabbits with 45 min ischemia, and the impact of ischemia on follicular survival and development status was evaluated at different time-points (1 day, 3 days, 1 week, 2 weeks and 1 month). Assessment of follicular quantity and morphology was carried out via histologic analysis. Follicle proliferating status was evidenced by immunostaining with proliferating cell nuclear antigen (PCNA), and the Hedgehog signaling pathway (Patched and Gli); was verified via TUNEL assay. Quantitative PCR was carried out to quantify the mRNA of target genes including PCNA, Patched, Gli, Caspase 3, Bax, and Bcl-2. Compared with its contralateral fresh controls, the morphology, proliferation and apoptosis of the follicles in the grafts showed no significant differences and most primordial follicles were quiescent. However, morphology and proliferation status were significantly decreased 1 week after grafting, in comparison with the longitudinal grafting time. Patched and Gli in the Hedgehog signaling pathway were activated in only the follicles of the grafts. Short-term ischemia slightly impacts follicular survival and development status in whole ovarian grafting. Receiving intervention in the first week post-transplantation might be helpful. PMID- 26271081 TI - Non-invasive cardiac imaging to unmask a very uncommon aetiology of an embolic stroke. PMID- 26271080 TI - Parental Monitoring, Parent-Adolescent Communication, and Adolescents' Trust in Their Parents in China. AB - PURPOSE: Trust is an important aspect of interpersonal relationships, but little is known about adolescents' interpersonal trust. The aim of the present study was to examine the associations among parental monitoring, parent-adolescent communication, and adolescents' trust in their parents in China. METHODS: Data in this study were collected as part of the cross-sectional study of children in China. 3349 adolescents (female 48.6%, age range of 12-15 years) were randomly selected from 35 secondary schools in April, 2009 and administered to the Adolescent Interpersonal Trust Scale, the Parental Monitoring Scale, and the Parent-Adolescent Communication Scale. RESULTS: Adolescents' trust in their parents was positively related to parental monitoring and parent-adolescent communication. Furthermore, parent-adolescent communication mediated the association between parental monitoring and adolescents' trust in their parents. The mediation model fit data of both genders and three age groups equally well. CONCLUSIONS: Parental monitoring and parent-adolescent communication play an importance role in fostering adolescents' trust in their parents. PMID- 26271082 TI - Intraocular Radio-Opaque Ring. AB - A radiologist noted a radio-opaque object in the eye of a woman undergoing X-ray examination to determine the safety of magnetic resonance imaging (MRI). Water's X-ray shows the titanium locking c-ring of a type 1 Boston keratoprosthesis. This ring was added in 2004 to prevent intraocular disassembly of the device. The nonmagnetic ring does not prevent MRI imaging. The titanium locking c-ring and the titanium or polymethyl methacrylate back plate of the Boston keratoprosthesis are safe for MRI imaging. PMID- 26271083 TI - Letter to the Editor: Subluxated Lens May Mimic Choroidal Metastasis of Cutaneous Malignant Melanoma. PMID- 26271084 TI - Current concepts in managing retinal vein occlusion in young patients. PMID- 26271085 TI - Diagnostic Imaging, Radiation Exposure, and Carcinogenic Risk: Let's Be Realistic, Reasonable, and Rational. PMID- 26271086 TI - Radiation Dose Reduction in Coronary CT Angiography: Time to Buckle Down. PMID- 26271088 TI - Detecting Skeletal Microvascular Flow Abnormalities in Diabetes: Could Microvascular Recruitment Be a Fundamental Problem? PMID- 26271087 TI - When Nothing Is Really Something: New Evidence of the Importance of Zero Coronary Calcium. PMID- 26271089 TI - Staphylococcus aureus Bloodstream Infection: When Is Transthoracic Echocardiography Sufficient? PMID- 26271090 TI - Left Ventricular Noncompaction: A Clinically Useful Diagnostic Label? PMID- 26271091 TI - Cardiovascular Imaging Research: Time to Think Beyond Risk Prediction? PMID- 26271092 TI - Transcatheter Valve Implantation in Failed Surgically Inserted Bioprosthesis: Review and Practical Guide to Echocardiographic Imaging in Valve-in-Valve Procedures. AB - An increased use of bioprosthetic heart valves has stimulated an interest in possible transcatheter options for bioprosthetic valve failure given the high operative risk. The encouraging results of transcatheter aortic valve implantation in high-risk surgical candidates with native disease have led to the development of the transcatheter valve-in-valve (VIV) procedures for failed bioprostheses. VIV procedures are unique in many ways, and there is an increased need for multimodality imaging in a team-based approach. The echocardiographic approach to VIV procedures has not previously been described. In this review, we summarize key echocardiographic requirements for optimal patient selection, procedural guidance, and immediate post-procedural assessment for VIV procedures. PMID- 26271093 TI - Contrast-Enhanced TEE During Thoracic Endovascular Aortic Repair Procedure. PMID- 26271094 TI - The Role of 3D Printing in Structural Heart Disease: All That Glitters Is Not Gold. PMID- 26271095 TI - Reply: The Role of 3D Printing in Structural Heart Disease: All That Glitters Is Not Gold. PMID- 26271096 TI - Is Seeing The Same As Knowing: The Dilemma of Imaging. PMID- 26271097 TI - Application of the Exradin W1 scintillator to determine Ediode 60017 and microDiamond 60019 correction factors for relative dosimetry within small MV and FFF fields. AB - In this work we use EBT3 film measurements at 10 MV to demonstrate the suitability of the Exradin W1 (plastic scintillator) for relative dosimetry within small photon fields. We then use the Exradin W1 to measure the small field correction factors required by two other detectors: the PTW unshielded Ediode 60017 and the PTW microDiamond 60019. We consider on-axis correction-factors for small fields collimated using MLCs for four different TrueBeam energies: 6 FFF, 6 MV, 10 FFF and 10 MV. We also investigate percentage depth dose and lateral profile perturbations. In addition to high-density effects from its silicon sensitive region, the Ediode exhibited a dose-rate dependence and its known over response to low energy scatter was found to be greater for 6 FFF than 6 MV. For clinical centres without access to a W1 scintillator, we recommend the microDiamond over the Ediode and suggest that 'limits of usability', field sizes below which a detector introduces unacceptable errors, can form a practical alternative to small-field correction factors. For a dosimetric tolerance of 2% on-axis, the microDiamond might be utilised down to 10 mm and 15 mm field sizes for 6 MV and 10 MV, respectively. PMID- 26271098 TI - Genetic ablation of caspase-7 promotes solar-simulated light-induced mouse skin carcinogenesis: the involvement of keratin-17. AB - Solar ultraviolet irradiation is an environmental carcinogen that causes skin cancer. Caspase-7 is reportedly expressed at reduced levels in many cancers. The present study was designed to examine the role of caspase-7 in solar-simulated light (SSL)-induced skin cancer and to elucidate its underlying molecular mechanisms. Our study revealed that mice with genetic deficiency of caspase-7 are highly susceptible to SSL-induced skin carcinogenesis. Epidermal hyperplasia, tumor volume and the average number of tumors were significantly increased in caspase-7 knockout (KO) mice compared with SKH1 wild-type mice irradiated with SSL. The expression of cell proliferation markers, such as survivin and Ki-67, was elevated in SSL-irradiated skin of caspase-7 KO mice compared with those observed in SSL-exposed wild-type SKH1 mouse skin. Moreover, SSL-induced apoptosis was abolished in skin from caspase-7 KO mice. Two-dimensional gel electrophoresis, followed by matrix-assisted laser desorption/ionization-time-of flight analysis of skin tissue lysates from SSL-irradiated SKH1 wild-type and caspase-7 KO mice revealed an aberrant induction of keratin-17 in caspase-7 KO mice. Immunohistochemical analysis of skin tumors also showed an increase of keratin-17 expression in caspase-7 KO mice compared with SKH1 wild-type mice. The expression of keratin-17 was also elevated in SSL-irradiated caspase-7 KO keratinocytes as well as in human basal cell carcinomas. The in vitro caspase activity assay showed keratin-17 as a substrate of caspase-7, but not caspase-3. Overall, our study demonstrates that genetic loss of caspase-7 promotes SSL induced skin carcinogenesis by blocking caspase-7-mediated cleavage of keratin 17. PMID- 26271100 TI - A Comparison of Ci/Gli Activity as Regulated by Sufu in Drosophila and Mammalian Hedgehog Response. AB - Suppressor of fused (Su(fu)/Sufu), one of the most conserved components of the Hedgehog (Hh) signaling pathway, binds Ci/Gli transcription factors and impedes activation of target gene expression. In Drosophila, the Su(fu) mutation has a minimal phenotype, and we show here that Ci transcriptional activity in large part is regulated independently of Su(fu) by other pathway components. Mutant mice lacking Sufu in contrast show excessive pathway activity and die as embryos with patterning defects. Here we show that in cultured cells Hh stimulation can augment transcriptional activity of a Gli2 variant lacking Sufu interaction and, surprisingly, that regulation of Hh pathway targets is nearly normal in the neural tube of Sufu-/- mutant embryos that also lack Gli1 function. Some degree of Hh-induced transcriptional activation of Ci/Gli thus can occur independently of Sufu in both flies and mammals. We further note that Sufu loss can also reduce Hh induction of high-threshold neural tube fates, such as floor plate, suggesting a possible positive pathway role for Sufu. PMID- 26271099 TI - Fat Metaplasia on Sacroiliac Joint Magnetic Resonance Imaging at Baseline Is Associated with Spinal Radiographic Progression in Patients with Axial Spondyloarthritis. AB - OBJECTIVE: To study the relationship between inflammatory and structural lesions in the sacroiliac joints (SIJs) on MRI and spinal progression observed on conventional radiographs in patients with axial spondyloarthritis (axSpA). METHODS: One hundred and ten patients who fulfilled the ASAS axSpA criteria were enrolled. All underwent SIJ MRI at baseline and lumbar spine radiographs at baseline and after 2 years. Inflammatory and structural lesions on SIJ MRI were scored using the SPondyloArthritis Research Consortium of Canada (SPARCC) method. Spinal radiographs were scored using the Stoke AS Spinal Score (SASSS). Multivariate logistic regression analysis was performed to identify predictors of spinal progression. RESULTS: Among the 110 patients, 25 (23%) showed significant radiographic progression (change of SASSS>=2) over 2 years. There was no change in the SASSS over 2 years according to the type of inflammatory lesion. Patients with fat metaplasia or ankyloses on baseline MRI showed a significantly higher SASSS at 2 years than those without (p<0.001). According to univariate logistic regression analysis, age at diagnosis, HLA-B27 positivity, the presence of fat metaplasia, erosion, and ankyloses on SIJ MRI, increased baseline CRP levels, and the presence of syndesmophytes at baseline were associated with spinal progression over 2 years. Multivariate analysis identified syndesmophytes and severe fat metaplasia on baseline SIJ MRI as predictive of spinal radiographic progression (OR, 14.74 and 5.66, respectively). CONCLUSION: Inflammatory lesions in the SIJs on baseline MRI were not associated with spinal radiographic progression. However, fat metaplasia at baseline was significantly associated with spinal progression after 2 years. PMID- 26271101 TI - The tRNA methyltransferase Dnmt2 is required for accurate polypeptide synthesis during haematopoiesis. AB - The Dnmt2 enzyme utilizes the catalytic mechanism of eukaryotic DNA methyltransferases to methylate several tRNAs at cytosine 38. Dnmt2 mutant mice, flies, and plants were reported to be viable and fertile, and the biological function of Dnmt2 has remained elusive. Here, we show that endochondral ossification is delayed in newborn Dnmt2-deficient mice, which is accompanied by a reduction of the haematopoietic stem and progenitor cell population and a cell autonomous defect in their differentiation. RNA bisulfite sequencing revealed that Dnmt2 methylates C38 of tRNA Asp(GTC), Gly(GCC), and Val(AAC), thus preventing tRNA fragmentation. Proteomic analyses from primary bone marrow cells uncovered systematic differences in protein expression that are due to specific codon mistranslation by tRNAs lacking Dnmt2-dependent methylation. Our observations demonstrate that Dnmt2 plays an important role in haematopoiesis and define a novel function of C38 tRNA methylation in the discrimination of near cognate codons, thereby ensuring accurate polypeptide synthesis. PMID- 26271104 TI - Initiation and preliminary evaluation of an oncology pharmacy training course for staff pharmacists. AB - INTRODUCTION: There is currently a disparity between oncology pharmacy job openings and PGY2 trained pharmacists completing residency training each year. As a result, pharmacists without specialized training in oncology are filling much needed oncology positions and may need on-the-job oncology training. To improve oncology knowledge among non-PGY2 trained pharmacists working in oncology positions, Novant Health coordinated an Oncology Pharmacy Training Course (OPTC). OBJECTIVES: The primary objective was to assess efficacy of the OPTC through evaluation of post-intervention oncology knowledge. Secondary objectives included efficacy of each lecture, assessment of knowledge improvement in those with and without residency or chemotherapy training, and assessment of satisfaction with the OPTC. METHODS: This was a prospective, cohort study. All pharmacists expressing interest in the OPTC were included unless PGY2 oncology residency trained or Board-Certified in Oncology Pharmacy (BCOP). Participants were invited to attend twice monthly lectures and were evaluated using questionnaires at baseline, 1, 3, 6, and 12 months. RESULTS: At the 3-month evaluation, 29 pharmacists completed the per-protocol evaluation. Knowledge scores increased from a mean of 29.6% to 52.2% (p < 0.01). Ten participants were chemotherapy trained. Baseline knowledge scores were slightly higher in the chemotherapy trained than training naive participants (mean 42.5% vs. 27.4%). Both groups experienced significantly improved knowledge scores at 3 months (mean 59% and 48.1% respectively, p < 0.01). DISCUSSION: Implementation of a formalized OPTC can improve oncology knowledge among staff pharmacists in a community hospital system. This improvement in knowledge is consistent regardless of baseline chemotherapy training. PMID- 26271105 TI - Stability of four standardized preparations of methotrexate, cytarabine, and hydrocortisone for intrathecal use. AB - INTRODUCTION: Intrathecal administration of methotrexate, cytarabine, and hydrocortisone is commonly used to treat and prevent central nervous system involvement in leukemias and lymphomas. The use of intrathecal solutions with pH and osmolarity values close to physiologic range of CSF (pH 7.31-7.37, osmolarity 281-306 mOsm/kg) and standardization of the methotrexate, cytarabine, and hydrocortisone doses in children and adults based on age is highly recommended. Stability studies of standardized intrathecal mixtures under these conditions have not yet been published. OBJECTIVE: The purpose of this study was to evaluate the physical and chemical stabilities of four standardized mixtures of methotrexate, cytarabine, and hydrocortisone stored at 2-8C and 25C up to 7 days after preparation. METHODS: Four different standardized intrathecal mixtures were prepared and stored at 2-8C and 25C and protected from light. Triplicate samples were taken at different times and precipitation, appearance, color, pH, and osmolarity were analyzed. Methotrexate, cytarabine, and hydrocortisone concentrations were measured using a modified high-performance liquid chromatography method. RESULTS: No variation greater than 10% of the initial concentration of methotrexate, cytarabine, and hydrocortisone was observed in any of the four standardized mixtures for the 7 days of study when stored at 2-8C and 25C and protected from light. The osmolarity of the four preparations was within the physiologic range of CSF for 7 days at both 2-8C and 25C. The pH values close to the physiologic range of CSF were stable for 48 h at 25C and for 120 h at 2 8C. CONCLUSIONS: Triple intrathecal standardized preparations of methotrexate, cytarabine, and hydrocortisone sodium phosphate are physically and chemically stable at 25C for 48 h and at 2-8C for 5 days. PMID- 26271103 TI - Notch signaling regulates gastric antral LGR5 stem cell function. AB - The major signaling pathways regulating gastric stem cells are unknown. Here we report that Notch signaling is essential for homeostasis of LGR5(+) antral stem cells. Pathway inhibition reduced proliferation of gastric stem and progenitor cells, while activation increased proliferation. Notch dysregulation also altered differentiation, with inhibition inducing mucous and endocrine cell differentiation while activation reduced differentiation. Analysis of gastric organoids demonstrated that Notch signaling was intrinsic to the epithelium and regulated growth. Furthermore, in vivo Notch manipulation affected the efficiency of organoid initiation from glands and single Lgr5-GFP stem cells, suggesting regulation of stem cell function. Strikingly, constitutive Notch activation in LGR5(+) stem cells induced tissue expansion via antral gland fission. Lineage tracing using a multi-colored reporter demonstrated that Notch-activated stem cells rapidly generate monoclonal glands, suggesting a competitive advantage over unmanipulated stem cells. Notch activation was associated with increased mTOR signaling, and mTORC1 inhibition normalized NICD-induced increases in proliferation and gland fission. Chronic Notch activation induced undifferentiated, hyper-proliferative polyps, suggesting that aberrant activation of Notch in gastric stem cells may contribute to gastric tumorigenesis. PMID- 26271102 TI - Collaborative protein filaments. AB - It is now well established that prokaryotic cells assemble diverse proteins into dynamic cytoskeletal filaments that perform essential cellular functions. Although most of the filaments assemble on their own to form higher order structures, growing evidence suggests that there are a number of prokaryotic proteins that polymerise only in the presence of a matrix such as DNA, lipid membrane or even another filament. Matrix-assisted filament systems are frequently nucleotide dependent and cytomotive but rarely considered as part of the bacterial cytoskeleton. Here, we categorise this family of filament-forming systems as collaborative filaments and introduce a simple nomenclature. Collaborative filaments are frequent in both eukaryotes and prokaryotes and are involved in vital cellular processes including chromosome segregation, DNA repair and maintenance, gene silencing and cytokinesis to mention a few. In this review, we highlight common principles underlying collaborative filaments and correlate these with known functions. PMID- 26271106 TI - Endothelial Activation Is Associated With Cognitive Performance in Patients With Hypertension. AB - BACKGROUND: Hypertension is associated with the occurrence of cognitive deficits and dementia, probably because hypertension is a major risk factor for the occurrence of brain damage as a result of cerebral small vessel disease (cSVD). Endothelial activation and inflammation have been suggested to play an important role in the pathogenesis of cSVD. We investigated if compound scores of endothelial activation or inflammation, based on several blood markers, are associated with cognitive performance 3 years later in patients with essential hypertension. METHODS: At baseline, levels of blood markers of endothelial activation (soluble vascular cellular adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), sP-selectin, and sE-selectin) and markers of inflammation (neopterin, C-reactive protein, and sICAM-1) were measured and transformed into compound scores using z-scores. In addition, a brain magnetic resonance imaging (MRI) was performed to determine the presence of cSVD-related MRI markers. Three years later, patients underwent a neuropsychological assessment to determine cognitive performance. RESULTS: A total of 101 patients with hypertension were included in the present study. In multiple linear regression analyses with correction for demographics and MRI markers, the compound score of endothelial activation (B = -0.19, 95% confidence interval = -0.34 to -0.04, P = 0.014), but not of inflammation (B = -0.09, 95% confidence interval = -0.22 to 0.05, P = 0.198), was associated with worse cognitive performance. CONCLUSIONS: Our results show that an overall measure of endothelial activation is associated with cognitive performance in patients with essential hypertension. This indicates that a process involving endothelial activation might play a role in the pathogenesis of cognitive problems in patients with hypertension. PMID- 26271108 TI - Association of Brachial-Ankle Pulse Wave Velocity With Cardiovascular Events in Atrial Fibrillation. AB - BACKGROUND: Atrial fibrillation (AF) and increased arterial stiffness share several risk factors and the 2 diseases often coexist. However, the prognostic value of increased arterial stiffness remains uncertain in the AF population. We evaluated whether brachial-ankle pulse wave velocity (baPWV), a marker of arterial stiffness, can predict cardiovascular events, and determined that the baPWV is a more favorable prognostic marker compared with conventional clinical and echocardiographic markers in patients with AF. METHODS: We enrolled 167 patients with persistent AF. Arterial stiffness was assessed using baPWV. Cardiovascular events were defined as cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, and hospitalization for heart failure. The relative risk of cardiovascular events was analyzed using Cox regression models. An improvement in model prediction was determined using the -2 log likelihood ratio statistic. RESULTS: During a median 26-month follow-up, 42 (24.9%) cardiovascular events were observed. The baPWV emerged as an independent predictor of cardiovascular events (adjusted hazard ratio: 1.152; 95% confidence interval: 1.054-1.259; P = 0.002) in the multivariate analysis. Furthermore, the addition of baPWV to a Cox model comprising standard clinical, biochemical, and echocardiographic parameters improved the prediction of adverse cardiovascular events (P < 0.001). CONCLUSIONS: In patients with AF, a high baPWV is associated with increased cardiovascular events and improve the prediction of adverse cardiovascular events. Hence, baPWV might be included when examining patients with AF for prediction of adverse cardiovascular outcomes. PMID- 26271109 TI - Blood Pressure Levels at the Time of Percutaneous Coronary Revascularization and Risk of Coronary In-Stent Restenosis. AB - BACKGROUND: High blood pressure (BP) levels expose patients treated with percutaneous coronary interventions (PCI) to very high risk of 10-year cardiovascular morbidity and mortality. OBJECTIVE: To investigate the role of BP levels at the time of PCI on the risk of in-stent restenosis (ISR). METHODS: We retrospectively included 796 patients previously treated with PCI, who underwent repeated angiography for recurrent angina or reversible myocardial ischemia. Patients were stratified into either case (n = 354) and control (n = 442) groups in the presence or absence of ISR (defined as in-stent diameter stenosis >=50%). BP levels were measured at the time of first and second procedures. Normal BP levels were defined for <140/90 mm Hg. RESULTS: Patients with normal BP showed significantly higher ISR-free survival (Log-rank: 5.937; P = 0.015). Both systolic (HR (95% CI): 0.731 (0.590-0.906)) and systolic/diastolic BP (HR (95% CI): 0.757 (0.611-0.939)) were significantly and independently associated with lower risk of ISR at Cox-regression analysis, adjusted for potential confounding factors, including stent type and concomitant medications. Patients with ISR showed lower rates of normal systolic/diastolic BP values (166 (47%) vs. 254 (57%); P = 0.003) compared to controls. They also received higher stent number (1.40+/-0.74 vs. 1.24+/-0.51; P < 0.001) with higher stent length (24.3+/-15.6 vs. 21.7+/-13.9 mm; P = 0.012), and lower rate of drug-eluting stents (DESs) (210 (48%) vs. 139 (40%); P = 0.025) compared to controls. CONCLUSIONS: Normal BP at the time of PCI is associated with nearly 24% risk reduction of ISR as evaluated in a new angiography in patients with coronary artery disease. PMID- 26271107 TI - Myocardial Performance Index in Childhood Onset Essential Hypertension and White Coat Hypertension. AB - BACKGROUND: As a global measure of ventricular systolic and diastolic function, the myocardial performance index (MPI) can be an early indicator of hypertensive cardiomyopathy in children with essential hypertension (EH). METHODS: Children with untreated newly diagnosed EH and white coat hypertension (WCH) by a 24-hour ambulatory blood pressure monitoring (ABPM), both groups without any identifiable etiology for the hypertension, were enrolled for the study. Echocardiograms and vascular ultrasounds for carotid artery intimal medial thickness were performed on all children prior to therapy. Diastolic function (peak E and A velocities, E/A ratio, isovolumic relaxation time, and deceleration times) and MPI were evaluated by simultaneous transmitral and transaortic spectral Doppler flow velocities. Systolic function was evaluated by shortening fraction and ejection fraction. RESULTS: A cohort of 66 children (24 with EH, 42 with WCH, males 61%, median age of 13 years, range 10-17 years) were enrolled in the study. The demographic, anthropometric, laboratory tests, vascular ultrasound, and conventional echocardiographic parameters were similar between the 2 groups. There was a very small difference in MPI between the EH and WCH children (0.28 SD: 0.07 vs. 0.31 SD: 0.08, P = 0.045). However, in EH children, MPI increased by 0.14 units for every 10 unit increase in mean ABPM systolic BP (95% confidence interval: 0.03-0.25). CONCLUSIONS: We found the increasing MPI was associated with increasing 24-hour mean systolic BP in children with EH. Therefore, MPI may have utility as a single, quick, noninvasive method of detection and tracking of subclinical hypertensive heart disease. PMID- 26271110 TI - Altered Human Memory Modification in the Presence of Normal Consolidation. AB - Following initial learning, the memory is stabilized by consolidation mechanisms, and subsequent modification of memory strength occurs via reconsolidation. Yet, it is not clear whether consolidation and memory modification are the same or different systems-level processes. Here, we report disrupted memory modification in the presence of normal consolidation of human motor memories, which relate to differences in lesioned brain structure after stroke. Furthermore, this behavioral dissociation was associated with macrostructural network architecture revealed by a graph-theoretical approach, and with white-matter microstructural integrity measured by diffusion-weighted MRI. Altered macrostructural network architecture and microstructural integrity of white-matter underlying critical nodes of the related network predicted disrupted memory modification. To the best of our knowledge, this provides the first evidence of mechanistic differences between consolidation, and subsequent memory modification through reconsolidation, in human procedural learning. These findings enable better understanding of these memory processes, which may guide interventional strategies to enhance brain function and resulting behavior. PMID- 26271111 TI - Functional Connectivity Patterns of Visual Cortex Reflect its Anatomical Organization. AB - The brain is continuously active, even without external input or task demands. This so-called resting-state activity exhibits a highly specific spatio-temporal organization. However, how exactly these activity patterns map onto the anatomical and functional architecture of the brain is still unclear. We addressed this question in the human visual cortex. We determined the representation of the visual field in visual cortical areas of 44 subjects using fMRI and examined resting-state correlations between these areas along the visual hierarchy, their dorsal and ventral segments, and between subregions representing foveal versus peripheral parts of the visual field. We found that retinotopically corresponding regions, particularly those representing peripheral visual fields, exhibit strong correlations. V1 displayed strong internal correlations between its dorsal and ventral segments and the highest correlation with LGN compared with other visual areas. In contrast, V2 and V3 showed weaker correlations with LGN and stronger between-area correlations, as well as with V4 and hMT+. Interhemispheric correlations between homologous areas were especially strong. These correlation patterns were robust over time and only marginally altered under task conditions. These results indicate that resting-state fMRI activity closely reflects the anatomical organization of the visual cortex both with respect to retinotopy and hierarchy. PMID- 26271112 TI - Differential Roles of Ventral and Dorsal Streams for Conceptual and Production Related Components of Tool Use in Acute Stroke Patients. AB - Impaired tool use despite preserved basic motor functions occurs after stroke in the context of apraxia, a cognitive motor disorder. To elucidate the neuroanatomical underpinnings of different tool use deficits, prospective behavioral assessments of 136 acute left-hemisphere stroke patients were combined with lesion delineation on magnetic resonance imaging (MRI) images for voxel based lesion-symptom mapping. Deficits affecting both the selection of the appropriate recipient for a given tool (ToolSelect, e.g., choosing the nail for the hammer), and the performance of the typical tool-associated action (ToolUse, e.g., hammering in the nail) were associated with ventro-dorsal stream lesions, particularly within inferior parietal lobule. However, ToolSelect compared with ToolUse deficits were specifically related to damage within ventral stream regions including anterior temporal lobe. Additional retrospective error dichotomization based on the videotaped performances of ToolUse revealed that spatio-temporal errors (movement errors) were mainly caused by inferior parietal damage adjacent to the intraparietal sulcus while content errors, that is, perplexity, unrecognizable, or semantically incorrect movements, resulted from lesions within supramarginal gyrus and superior temporal lobe. In summary, our results suggest that in the use of tools, conceptual and production-related aspects can be differentiated and are implemented in anatomically distinct streams. PMID- 26271114 TI - More than Light Alcohol Consumption Predicts Early Cessation from Employment in French Middle-Aged Men. AB - AIMS: To investigate the association between alcohol consumption and different causes of work cessation and estimate the loss of occupational activity among high consumers compared with low consumers. METHODS: From the prospective study of men employed in the French gas and electric company, 8442 men during a median follow-up of 8.4 years reported on their alcohol consumption. Information on work cessation was collected from the company administrative records. Hazard Ratios (HRs) by cause of work cessation (death, disability, retirement before or after age 55) were estimated using a competing risk method. RESULTS: An increasing quantity of daily alcohol consumption was associated with an increased risk of death, disability and retirement before age 55 (P trend <= 0.01, = 0.03 and <= 0.01, respectively), but not of retirement after age 55 (P trend = 0.56). Moreover, compared with low consumption, moderate, high or very high daily intakes were associated with an increased risk of early work cessation (combination of the three causes: death, disability and retirement before age 55) (HR = 1.14, 95% confidence interval (CI) = 1.05-1.25; HR = 1.23, 95% CI = 1.12 1.35 and HR = 1.49, 95% CI = 1.15-1.92 respectively). Between ages 50 and 60, we estimated that high or very high consumers could gain 6.04 months of occupational activity if they drank like low consumers. CONCLUSIONS: Our results provide evidence of a dose-effect relationship between alcohol consumption and early work cessation. PMID- 26271115 TI - GET73 Prevents Ethanol-Induced Neurotoxicity in Primary Cultures of Rat Hippocampal Neurons. AB - AIMS: N-[(4-trifluoromethyl) benzyl] 4-methoxybutyramide (GET73) may be considered a promising therapeutic agent for the treatment of alcohol use disorders. The compound displayed anti-alcohol and anxiolytic properties in rat. In the present study, an in vitro experimental model of chronic ethanol treatment was used to investigate the ability of the compound to counteract the ethanol induced neurotoxicity. METHODS: Primary cultures of rat hippocampal neurons were exposed to ethanol (75 mM; 4 days) and the neuroprotective effects of GET73 were assessed by evaluating cell viability, cell morphology, glutamate levels and reactive oxygen species production. RESULTS: The exposure to ethanol induced a reduction of cell viability, an alteration of cytoskeleton, a decrease in extracellular glutamate levels and an increase of reactive oxygen species production. The addiction of GET73 (1 and 10 uM) 1 h before and during chronic ethanol exposure prevented all the above ethanol-induced effects. Based on the proposed GET73 mechanism of action, the effects of mGlu5 receptor negative allosteric modulator, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), on ethanol induced reduction of cell viability were also assessed. The results indicated that the addiction of MPEP (100 uM) 1 h before and during chronic ethanol exposure prevented the ethanol-induced cell viability reduction. CONCLUSION: The present findings provide the first evidence that GET73 shows a neuroprotective role against ethanol-induced neurotoxicity in primary cultures of rat hippocampal neurons. Together with previous findings, these results suggest that GET73 possesses multifaceted properties thus lending further support to the significance of developing GET73 as a therapeutic tool for use in the treatment of alcohol use disorders. PMID- 26271117 TI - Do changes in neighborhood and household levels of smoking and deprivation result in changes in individual smoking behavior? A large-scale longitudinal study of New Zealand adults. AB - Health behavior takes place within social contexts. In this study, we investigated whether changes in exposure to neighborhood deprivation and smoking prevalence and to household smoking were associated with change in personal smoking behavior. Three waves of biannual data collection (2004-2009) in a New Zealand longitudinal study, the Survey of Family, Income and Employment (SoFIE) Health, were used, with 13,815 adults (persons aged >=15 years) contributing to the analyses. Smoking status was dichotomized as current smoking versus never/ex smoking. Fixed-effects regression analyses removed time-invariant confounding and adjusted for time-varying covariates (neighborhood smoking prevalence and deprivation, household smoking, labor force status, income, household tenure, and family status). A between-wave decile increase in neighborhood deprivation was significantly associated with increased odds of smoking (odds ratio (OR) = 1.08, 95% confidence interval (CI): 1.02, 1.14), but a between-wave increase in neighborhood smoking prevalence was not (OR = 1.04, 95% CI: 0.98, 1.10). Changing household exposures between waves to live with another smoker (compared with a nonsmoker (referent)) increased the odds of smoking (OR = 2.48, 95% CI: 1.84, 3.34), as did changing to living in a sole-adult household (OR = 1.52, 95% CI: 1.07, 2.14). Tobacco control policies and programs should address the broader household and neighborhood circumstances within which individual smoking takes place. PMID- 26271116 TI - Common immune-related exposures/conditions and risk of non-Hodgkin lymphoma: a case-control study of disease-discordant twin pairs. AB - We evaluated the association between common immune system-altering experiences and non-Hodgkin lymphoma (NHL) risk using a case-control study of 162 like-sex twin pairs discordant for NHL, identified from the International Twin Study. Information on medical history and evidence of childhood exposure to microbes was obtained by questionnaire from 1998 to 2002. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals. Intra-twin-pair agreement between twins on individual exposures was high (76%-97%). A negative association between NHL and seasonal hay fever (odds ratio (OR) = 0.28, 95% confidence interval (CI): 0.10, 0.75) and certain allergies (OR = 0.29, 95% CI: 0.13, 0.68) was observed. The number of atopic diseases was negatively associated with NHL (P for trend = 0.0003). A history of infectious mononucleosis was negatively associated with NHL risk (OR = 0.35, 95% CI: 0.14, 0.90). NHL risk was associated with more frequent childhood exposure to microbes during early life (P for trend = 0.04). No differences in association by NHL subtype were observed, although statistical power for these comparisons was low. These observations support the hypothesis that immune-related exposures, especially atopy, are associated with decreased NHL risk. Use of the within-twin-pair study design mitigates confounding by genome, family structure, and unmeasured characteristics of early childhood factors. PMID- 26271113 TI - From Phineas Gage and Monsieur Leborgne to H.M.: Revisiting Disconnection Syndromes. AB - On the 50th anniversary of Norman Geschwind's seminal paper entitled 'Disconnexion syndrome in animal and man', we pay tribute to his ideas by applying contemporary tractography methods to understand white matter disconnection in 3 classic cases that made history in behavioral neurology. We first documented the locus and extent of the brain lesion from the computerized tomography of Phineas Gage's skull and the magnetic resonance images of Louis Victor Leborgne's brain, Broca's first patient, and Henry Gustave Molaison. We then applied the reconstructed lesions to an atlas of white matter connections obtained from diffusion tractography of 129 healthy adults. Our results showed that in all 3 patients, disruption extended to connections projecting to areas distant from the lesion. We confirmed that the damaged tracts link areas that in contemporary neuroscience are considered functionally engaged for tasks related to emotion and decision-making (Gage), language production (Leborgne), and declarative memory (Molaison). Our findings suggest that even historic cases should be reappraised within a disconnection framework whose principles were plainly established by the associationist schools in the last 2 centuries. PMID- 26271118 TI - Germination and seedling establishment in orchids: a complex of requirements. AB - BACKGROUND: Seedling recruitment is essential to the sustainability of any plant population. Due to the minute nature of seeds and early-stage seedlings, orchid germination in situ was for a long time practically impossible to observe, creating an obstacle towards understanding seedling site requirements and fluctuations in orchid populations. The introduction of seed packet techniques for sowing and retrieval in natural sites has brought with it important insights, but many aspects of orchid seed and germination biology remain largely unexplored. KEY CONSIDERATIONS: The germination niche for orchids is extremely complex, because it is defined by requirements not only for seed lodging and germination, but also for presence of a fungal host and its substrate. A mycobiont that the seedling can parasitize is considered an essential element, and a great diversity of Basidiomycota and Ascomycota have now been identified for their role in orchid seed germination, with fungi identifiable as imperfect Rhizoctonia species predominating. Specificity patterns vary from orchid species employing a single fungal lineage to species associating individually with a limited selection of distantly related fungi. A suitable organic carbon source for the mycobiont constitutes another key requirement. Orchid germination also relies on factors that generally influence the success of plant seeds, both abiotic, such as light/shade, moisture, substrate chemistry and texture, and biotic, such as competitors and antagonists. Complexity is furthermore increased when these factors influence seeds/seedling, fungi and fungal substrate differentially. CONCLUSIONS: A better understanding of germination and seedling establishment is needed for conservation of orchid populations. Due to the obligate association with a mycobiont, the germination niches in orchid species are extremely complex and varied. Microsites suitable for germination can be small and transient, and direct observation is difficult. An experimental approach using several levels of environmental manipulation/control is recommended. PMID- 26271119 TI - Seed birth to death: dual functions of reactive oxygen species in seed physiology. AB - BACKGROUND: Reactive oxygen species (ROS) are considered to be detrimental to seed viability. However, recent studies have demonstrated that ROS have key roles in seed germination particularly in the release of seed dormancy and embryogenesis, as well as in protection from pathogens. SCOPE: This review considers the functions of ROS in seed physiology. ROS are present in all cells and at all phases of the seed life cycle. ROS accumulation is important in breaking seed dormancy, and stimulating seed germination and protection from pathogens. However, excessive ROS accumulation can be detrimental. Therefore, knowledge of the mechanisms by which ROS influence seed physiology will provide insights that may not only allow the development of seed quality markers but also help us understand how dormancy can be broken in several recalcitrant species. CONCLUSIONS: Reactive oxygen species have a dual role in seed physiology. Understanding the relative importance of beneficial and detrimental effects of ROS provides great scope for the improvement and maintenance of seed vigour and quality, factors that may ultimately increase crop yields. PMID- 26271121 TI - Immediate Large-Volume Grafting of Autologous Fat to the Breast Following Implant Removal. AB - BACKGROUND: To optimize autologous breast augmentation, a simple and reproducible surgical approach that maximizes the volume of fat transferred to the breast while minimizing the number of sessions and the operating time is needed. OBJECTIVES: The authors describe a novel approach for large-volume fat grafting to the expanded skin and subcutaneous tissue of the breast immediately after explantation, exchanging the volume provided by the implants with transplanted fat in a single session. METHODS: Eighty patients (160 breasts) undergoing explantation and autologous fat transfer were evaluated in a prospective study. Fat was harvested with the lipomatic power-assisted liposuction machine (Lipomatic Eva SP, Euromi SA, Verviers, Belgium) and was injected with simultaneous vibration and tunnelization of the recipient site by means of the same machine with suction disabled. Changes in breast volume were measured in terms of bra cup size, and patients were monitored by mammography and ultrasonography. Patient satisfaction was assessed with a questionnaire administered 6 months postoperatively. RESULTS: Injected fat volumes ranged from 300 to 600 mL per breast. Operating times ranged from 45 to 90 minutes. For all patients, one injection session was sufficient to replace the volume of the previous implant. Patients were monitored for an average of 2 years, and complications included cyst formation in 9 of 160 breasts (5.6%) and infection in 2 breasts (1.25%). CONCLUSIONS: Power-assisted transfer of autologous fat to the breast improves the ability of the recipient site to receive the graft and allows for explantation and fat transplantation in a single session. This approach is suitable for patients who desire a natural-appearing breast that is similar in volume to their previous implant. PMID- 26271120 TI - Cryptococcal phosphoglucose isomerase is required for virulence factor production, cell wall integrity and stress resistance. AB - Regulation of virulence factor production in the pathogen Cryptococcus neoformans remains to be fully illustrated. We present here a finding that a gene, encoding the glycolysis enzyme phosphoglucose isomerase (Pgi1), is critical for the biosynthesis of melanin and capsule, cell wall integrity and resistance to stress conditions. A leaky mutant of the yeast, LZM19, resulted from an insertion of T DNA in the PGI1 promoter region, expressed PGI1 at a level only 1.9% of the wild type. LZM19 could synthesize the pigment melanin in the presence of 2% glucose, suggesting a status of LAC1 derepression. Phenotypically, capsule biosynthesis in LZM19 was remarkably reduced. Integrity of the cell wall and plasma membrane of LZM19 were impaired based on its sensitivity to Congo red and SDS. Also, LZM19 exhibited hypersensitivity to osmotic stress generated by 2 M NaCl or 1 M KCl, indicating possible impairment in the HOG signaling pathway. Furthermore, LZM19 failed to utilize mannose and fructose, suggesting a possible involvement of Pgi1 in the breakdown of these two sugars. Our results revealed a crucial role of PGI1 in coordination of the production of virulence factors, cell wall integrity and stress response in C. neoformans. PMID- 26271122 TI - Concomitant Overlap Steal Tip-plasty: A Versatile Technique to Simultaneously Adjust the Rotation, Definition, Projection, and Symmetry of the Nasal Tip. AB - BACKGROUND: Tip-plasty is a particularly challenging stage of aesthetic nose surgery. The diversity of nasal tip deformities has necessitated the development of numerous surgical techniques that can be difficult to master and may yield unpredictable surgical results when combined. OBJECTIVES: The authors describe how concomitant overlap steal tip-plasty (COST) can enable surgeons to address all of the aesthetic characteristics of the nasal tip simultaneously. COST involves lateral crural steal followed by medial crural overlap. METHODS: The medical records of 1617 patients who underwent primary open septorhinoplasty with COST were evaluated in a retrospective study. Pre- and postoperative patient photographs were compared for nasal length, nasolabial angle, tip projection, and deviation of the nasal axis. RESULTS: Pre- and postoperative mean nasal lengths were 5.66 cm and 5.17 cm, respectively (P < .05). The mean nasolabial angle was 86.95 degrees preoperatively and 101.8 degrees postoperatively (P < .05). The projection of the nasal tip was reduced from 3.09 cm to 2.53 cm, and tip symmetry was achieved by decreasing the nasal axis deviation from 7.76 degrees to 1.71 degrees (both P < .05). CONCLUSIONS: COST does not obviate all other tip-plasty techniques for specific situations. Once mastered, however, COST can become the only procedure needed to achieve all of the aesthetic goals of the nasal tip in most cases. LEVEL OF EVIDENCE 4: Therapeutic. PMID- 26271123 TI - Food capacities and satisfaction in participants in food security community interventions in Montreal, Canada. AB - Food insecurity is steadily increasing in Canada. The objective of this paper is to determine if food capacities and satisfaction of recently enrolled participants in food security interventions are associated with the intervention having either a traditional or an alternative type of approach. Participants having recently accessed traditional (n = 711) or alternative community interventions (n = 113) in the Montreal metropolitan area, Canada, were interviewed with a questionnaire. The categorizing variable was participation in a community organization providing either traditional interventions, aimed to help people cope with the urgent need of food, or alternative interventions, aimed at first assistance, in addition to the creation of long-term solutions such as social integration and skills development. Participants' food and nutrition-related capacities and food satisfaction are studied. Multilevel regression models were used to assess whether participants took part in a traditional or alternative interventions. These interventions do not reach the same population. Relative to participants in alternative food security interventions, participants in traditional interventions demonstrated less capacity for accessing information about food safety and healthiness, and perceived their diet as less healthy. Traditional food security participants also paid less attention to the nutritional properties of food and reported less satisfaction with quantity, variety and taste of the food they accessed. The reasons why individuals who may benefit the most from alternative interventions were unlikely to participate should be investigated. The potential that food security interventions may inadvertently reinforce social inequalities in health should be considered in future intervention research. PMID- 26271124 TI - Whole body computed tomography for trauma patients in the Nordic countries 2014: survey shows significant differences and a need for common guidelines. AB - BACKGROUND: Whole body computed tomography in trauma (WBCTT) is a standardized CT examination of trauma patients. It has a relatively high radiation dose. Therefore, well-defined clinical indications and imaging protocols are needed. This information regarding Nordic countries is limited. PURPOSE: To identify Nordic countries' WBCTT imaging protocols, radiation dose, and integration in trauma care, and to inquire about the need for common Nordic guidelines. MATERIAL AND METHODS: A survey with 23 multiple choice questions or free text responses was sent to 95 hospitals and 10 trauma centers in and outside the Nordic region, respectively. The questions were defined and the hospitals selected in collaboration with board members of "Nordic Forum for Trauma and Emergency Radiology" (www.nordictraumarad.com). RESULTS: Two Nordic hospitals declined to take part in the survey. Out of the remaining 93 Nordic hospitals, 56 completed the questionnaire. Arterial visualization is routine in major trauma centers but only in 50% of the Nordic hospitals. The CT scanner is located within 50 m of the emergency department in all non-Nordic trauma centers but only in 60% of Nordic hospitals. Radiation dose for WBCTT is in the range of 900-3600 mGy * cm. Of the 56 responding Nordic hospitals, 84% have official guidelines for WBCTT. Eighty nine percent of the responders state there is a need for common guidelines. CONCLUSION: Scanning protocols, radiation doses, and routines differ significantly between hospitals and trauma centers. Guideline for WBCTT is presently defined locally in most Nordic hospitals. There is an interest in most Nordic hospitals to endorse new and common guidelines for WBCTT. PMID- 26271126 TI - Male doctors are more likely to have legal action taken against them, analysis finds. PMID- 26271125 TI - CT texture analysis can help differentiate between malignant and benign lymph nodes in the mediastinum in patients suspected for lung cancer. AB - BACKGROUND: In patients with non-small-cell lung carcinoma NSCLC the lymph node staging in the mediastinum is important due to impact on management and prognosis. Computed tomography texture analysis (CTTA) is a postprocessing technique that can evaluate the heterogeneity of marked regions in images. PURPOSE: To evaluate if CTTA can differentiate between malignant and benign lymph nodes in a cohort of patients with suspected lung cancer. MATERIAL AND METHODS: With tissue sampling as reference standard, 46 lymph nodes from 29 patients were analyzed using CTTA. For each lymph node, CTTA was performed using a research software "TexRAD" by drawing a region of interest (ROI) on all available axial contrast-enhanced computed tomography (CT) slices covering the entire volume of the lymph node. Lymph node CTTA comprised image filtration-histogram analysis undertakes two stages: the first step comprised an application of a Laplacian of Gaussian filter to highlight fine to coarse textures within the ROI, followed by a quantification of textures via histogram analysis using mean gray-level intensity from the entire volume of the lymph nodes. RESULTS: CTTA demonstrated a statistically significant difference between the malignant and the benign lymph nodes (P = 0.001), and by binary logistic regression we obtained a sensitivity of 53% and specificity of 97% in the test population. The area under the receiver operating curve was 83.4% and reproducibility was excellent. CONCLUSION: CTTA may be helpful in differentiating between malignant and benign lymph nodes in the mediastinum in patients suspected for lung cancer, with a low intra-observer variance. PMID- 26271127 TI - Meta-Analysis Comparing Rosuvastatin and Atorvastatin in Reducing Concentration of C-Reactive Protein in Patients With Hyperlipidemia. AB - We conducted a meta-analysis of 13 randomized trials comparing the efficacy of rosuvastatin versus atorvastatin in reducing concentrations of C-reactive protein (CRP). We searched PubMed, Ovid, and Elsevier databases until June 2014. Search terms included C-reactive protein or CRP, rosuvastatin, atorvastatin, randomized, randomly, and randomization; 13 trials (3798 patients) were included. Funnel plots for CRP were inspected to assess publication bias. The pooled analysis demonstrated the benefit of rosuvastatin over atorvastatin therapy for all 13 trials (mean difference [MD] = -0.11, which is standardized mean with no unit although the raw data before pooling is mg/L, 95% confidence interval -0.15 to 0.07, P < .0001) with no evidence of significant publication bias (I(2) = 6.9%, P = .377). Subgroup analysis indicated a significant benefit of rosuvastatin over atorvastatin regarding the 1/1 dose ratio (MD = -0.14, 95% CI -0.21 to -0.06) and 1/2 dose ratio (MD= -0.11, 95% CI -0.16 to -0.05). Cumulative and influence analyses showed accuracy and stability for the estimation mentioned earlier. Our meta-analysis shows that rosuvastatin produces better reduction in CRP concentrations than atorvastatin at a dose ratio of 1/1 and 1/2 (rosuvastatin/atorvastatin), respectively. PMID- 26271129 TI - Strategic Ability Updating in Concurrent Games by Coalitional Commitment. AB - Strategic ability updating relates to establishing some required properties, which can be expressed by strategic abilities, in a multicomponent reactive system. We model such a reactive system as a concurrent game structure (CGS), which is the semantic model of Alternating-time Temporal Logic (ATL). Then, we propose coalitional commitment as a tool for achieving the required strategic ability updating. Intuitively, a coalitional commitment can extend the state space of a CGS by a context function and then delete some transitions by a coalitional normative system (CNS). We propose coordinated ATL (co-ATL) for reasoning about strategic abilities in the structures obtained from a CGS by implementing a CNS. The model-checking problem for co-ATL is proved to be PTIME complete, just like that of ATL, and is thus tractable. Then, we characterize the limitation of coalitional commitment power by identifying the set of co-ATL formulas whose satisfaction cannot be established and the set of co-ATL formulas whose satisfaction cannot be avoided. Afterward, we show that the effectiveness problem, feasibility problem, and synthesis problem for coalitional commitment are PTIME-complete, NP-complete, and FNP-complete, respectively. Finally, we treat the coalitional commitment synthesis problem as an extended planning problem and present an algorithm based on the planning as model checking paradigm. Our work can be seen as an improvement for both social law research and planning via model checking research. PMID- 26271128 TI - Anemia and Outcome in Outpatients With Peripheral Artery Disease. AB - The influence of anemia on outcome in stable outpatients with peripheral artery disease (PAD) has not been consistently investigated. We used data from the Factores de Riesgo y ENfermedad Arterial (FRENA) Registry to compare ischemic events and mortality rates in stable outpatients with symptomatic PAD and anemia. Of 1663 patients with PAD, 208 (12.5%) had anemia. Over 18 months, patients with anemia had a higher rate of myocardial infarction (MI; rate ratio [RR]: 2.10; 95% confidence interval [CI]: 1.04-3.99), limb amputation (RR: 2.98; 95%CI: 1.70 5.05), and higher mortality (RR: 3.58; 95%CI: 2.39-5.28) than those without anemia. The rates of ischemic stroke (RR: 0.75; 95%CI: 0.23-1.93) and major bleeding (RR: 0.93; 95%CI: 0.15-3.51) were similar. On multivariable analysis, anemia was associated with an increased risk to die (hazard ratio [HR]: 2.32; 95%CI: 1.53-3.50) but not to develop MI (HR: 1.49; 95%CI: 0.73-3.05) or to have limb amputation (HR: 1.49; 95%CI: 0.86-2.59). In stable outpatients with PAD, anemia was associated with increased mortality but not with an increased rate of subsequent ischemic events or major bleeding. PMID- 26271130 TI - Augmented Complex Common Spatial Patterns for Classification of Noncircular EEG From Motor Imagery Tasks. AB - A novel augmented complex-valued common spatial pattern (CSP) algorithm is introduced in order to cater for general complex signals with noncircular probability distributions. This is a typical case in multichannel electroencephalogram (EEG), due to the power difference or correlation between the data channels, yet current methods only cater for a very restrictive class of circular data. The proposed complex-valued CSP algorithms account for the generality of complex noncircular data, by virtue of the use of augmented complex statistics and the strong-uncorrelating transform (SUT). Depending on the degree of power difference of complex signals, the analysis and simulations show that the SUT based algorithm maximizes the inter-class difference between two motor imagery tasks. Simulations on both synthetic noncircular sources and motor imagery experiments using real-world EEG support the approach. PMID- 26271131 TI - Objective Automatic Assessment of Rehabilitative Speech Treatment in Parkinson's Disease. AB - Vocal performance degradation is a common symptom for the vast majority of Parkinson's disease (PD) subjects, who typically follow personalized one-to-one periodic rehabilitation meetings with speech experts over a long-term period. Recently, a novel computer program called Lee Silverman voice treatment (LSVT) Companion was developed to allow PD subjects to independently progress through a rehabilitative treatment session. This study is part of the assessment of the LSVT Companion, aiming to investigate the potential of using sustained vowel phonations towards objectively and automatically replicating the speech experts' assessments of PD subjects' voices as "acceptable" (a clinician would allow persisting during in-person rehabilitation treatment) or "unacceptable" (a clinician would not allow persisting during in-person rehabilitation treatment). We characterize each of the 156 sustained vowel /a/ phonations with 309 dysphonia measures, select a parsimonious subset using a robust feature selection algorithm, and automatically distinguish the two cohorts (acceptable versus unacceptable) with about 90% overall accuracy. Moreover, we illustrate the potential of the proposed methodology as a probabilistic decision support tool to speech experts to assess a phonation as "acceptable" or "unacceptable." We envisage the findings of this study being a first step towards improving the effectiveness of an automated rehabilitative speech assessment tool. PMID- 26271132 TI - [Impacts on neutrophil to lymphocyte ratio in patients of chronic stable angina pectoris treated with acupuncture at Neiguan (PC 6)]. AB - OBJECTIVE: To observe the clinical efficacy on chronic stable angina pectoris treated with acupuncture at Neiguan (PC 6) and explore the impacts of acupuncture on peripheral blood neutrophil to lymphocyte ratio (NLR) in the patients of stable angina pectoris. METHODS: Thirty patients of chronic stable angina pectoris met the inclusive criteria were randomized into an acupuncture group (15 cases) and a medication group (15 cases), and a healthy control group (15 cases of the same ages) was set up separately. In the acupuncture group, at the same time of the basic medication, acupuncture was applied to bilateral Neiguan (PC 6), once every two days, 3 days a week, totally for 4 weeks. In the medication group, the basic medication was applied, without acupuncture intervention. In the healthy control group, no any intervention was applied. The attack frequency of angina pectoris, dose of nitrogly-cerin, the evaluation of visual analogue scale (VAS), Seattle angina questionnaire (SAQ), the six-minute walking test (6MWT), the self-rating anxiety scale (SAS) and the self-rating depression scale (SDS) were observed before and after treatment in the subjects. Additionally, the peripheral blood cells were detected to analyze specifically the changes in NLR before and after treatment and observe the relationship between NLR and clinical efficacy. RESULTS: Compared with the medication group, the attack frequency of angina pectoris was reduced within 30 days (P<0.01); the dose of nitroglycerin was reduced (P<0.01); VAS was reduced (P<0.01) and SAQ was increased (P<0.05) in the acupuncture group. The differences in 6 MWT, SAS and SDS were not significant between the two groups after treatment (all P>0.05). Additionally, compared with the medication group, in 30 days of acupuncture, NLR was reduced apparently in the acupuncture group (P<0.05). CONCLUSION: Acupuncture relieves the clinical symptoms of chronic stable angina pectoris, but has not apparent effects on motor ability and psychological health. Corresponding to that before treatment, the decreased NRL in the patients of acupuncture group suggests the potential good prognosis on coronary heart disease after acupuncture. PMID- 26271134 TI - Remembering Connie: A Life and Legacy That Just Keeps Giving. PMID- 26271135 TI - Assessing potential divers with a history of congenital heart disease. AB - This article describes a structured approach to assessing the medical fitness of potential divers who have a history of congenital heart disease. The importance of a complete and accurate cardiac history, including details of surgery and other interventions is emphasized. Specific assessment of intracardiac shunts, exercise capacity and ability to deal with the physical challenge of diving, risk of diving-included pulmonary oedema, of arrhythmia and of incapacity in case of arrhythmia and the consequences of surgical and catheter treatment are discussed, including the risks associated with lung injury and the pressure limitations of implanted devices like pacemakers. Clinical assessment will usually include echocardiography and exercise testing with additional investigations such as MRI scanning, CT of heart or lungs, cardiopulmonary exercise testing and ECG monitoring, as required. Examples of different congenital lesions are given applying this approach (atrial septal defect, tetralogy of Fallot, bicuspid aortic valve and the Fontan circulation). The approach is based on an individual cardiologist's opinion and is not specifically evidence-based, but seeks to apply what is known in other areas of diving medicine to this potentially complex group of patients. PMID- 26271137 TI - [Abstracts of the 2th Congress of the Hungarian Radiotherapy Association, May 14 16, 2015, Kecskemet, Hungary]. PMID- 26271136 TI - Codon usage patterns in Nematoda: analysis based on over 25 million codons in thirty-two species. AB - BACKGROUND: Codon usage has direct utility in molecular characterization of species and is also a arker for molecular evolution. To understand codon usage within the diverse phylum Nematoda,we analyzed a total of 265,494 expressed sequence tags (ESTs) from 30 nematode species. The full genomes of Caenorhabditis elegans and C. briggsae were also examined. A total of 25,871,325 codons ere analyzed and a comprehensive codon usage table for all species was generated. This is the first codon usage table available for 24 of these organisms. RESULTS: Codon usage similarity in Nematoda usually persists over the breadth of a genus but thenrapidly diminishes even within each clade. Globodera, Meloidogyne, Pristionchus, and Strongyloides have the most highly derived patterns of codon usage. The major factor affecting differences in codon usage between species is the coding sequence GC content, which varies in nematodes from 32%to 51%. Coding GC content (measured as GC3) also explains much of the observed variation in the effective number of codons (R = 0.70), which is a measure of codon bias, and it even accounts for differences in amino acid frequency. Codon usage is also affected by neighboring nucleotides(N1 context). Coding GC content correlates strongly with estimated noncoding genomic GC content (R = 0.92). On examining abundant clusters in five species, candidate optimal codons were identified that may be preferred in highly expressed transcripts. CONCLUSION: Evolutionary models indicate that total genomic GC content, probably the product of directional mutation pressure, drives codon usage rather than the converse, a conclusion that is supported by examination of nematode genomes. PMID- 26271139 TI - Serum Lipid and Serum Metabolite Components in relation to anthropometric parameters in EPIC-Potsdam participants. AB - BACKGROUND/AIM: Lipidomic and metabolomic techniques become more and more important in human health research. Recent developments in analytical techniques enable the investigation of high amounts of substances. The high numbers of metabolites and lipids that are detected with among others mass spectrometric techniques challenge in most cases the statistical processes to bring out stable and interpretable results. This study targets to use the novel non-established statistical method treelet transform (TT) to investigate high numbers of metabolites and lipids and to compare the results with the established method principal component analysis (PCA). Serum lipid and metabolite profiles are investigated regarding their association to anthropometric parameters associated to obesity. METHODS: From 226 participants of the EPIC (European Prospective Investigation into Cancer and Nutrition)-Potsdam study blood samples were investigated with an untargeted metabolomics approach regarding serum metabolites and lipids. Additionally, participants were surveyed anthropometrically to assess parameters of obesity, such as body mass index (BMI), waist-to-hip-ratio (WHR) and body fat mass. TT and PCA are used to generate treelet components (TCs) and factors summarizing serum metabolites and lipids in new, latent variables without too much loss of information. With partial correlations TCs and factors were associated to anthropometry under the control for relevant parameters, such as sex and age. RESULTS: TT with metabolite variables (p=121) resulted in 5 stable and interpretable TCs explaining 18.9% of the variance within the data. PCA on the same variables generated 4 quite complex, less easily interpretable factors explaining 37.5% of the variance. TT on lipidomic data (p=353) produced 3 TCs as well as PCA on the same data resulted in 3 factors; the proportion of explained variance was 17.8% for TT and 39.8% for PCA. In both investigations TT ended up with stable components that are easier to interpret than the factors from the PCA. In general, the generated TCs and factors were similar in their structure when the factors are considered regarding the original variables loading high on them. Both TCs and factors showed associations to anthropometric measures. CONCLUSIONS: TT is a suitable statistical method to generate summarizing, latent variables in data sets with more variables than observations. In the present investigation it resulted in similar latent variables compared to the established method of PCA. Whereby less variance is explained by the summarizing constructs of TT compared to the factors of PCA, TCs are easier to interpret. Additionally the resulting TCs are quite stable in bootstrap samples. PMID- 26271138 TI - Does health insurance mitigate inequities in non-communicable disease treatment? Evidence from 48 low- and middle-income countries. AB - Non-communicable diseases (NCDs) are the greatest contributor to morbidity and mortality in low- and middle-income countries (LMICs). However, NCD care is limited in LMICs, particularly among the disadvantaged and rural. We explored the role of insurance in mitigating socioeconomic and urban-rural disparities in NCD treatment across 48 LMICs included in the 2002-2004 World Health Survey (WHS). We analyzed data about ever having received treatment for diagnosed high-burden NCDs (any diagnosis, angina, asthma, depression, arthritis, schizophrenia, or diabetes) or having sold or borrowed to pay for healthcare. We fit multivariable regression models of each outcome by the interaction between insurance coverage and household wealth (richest 20% vs. poorest 50%) and urbanicity, respectively. We found that insurance was associated with higher treatment likelihood for NCDs in LMICs, and helped mitigate socioeconomic and regional disparities in treatment likelihood. These influences were particularly strong among women. Insurance also predicted lower likelihood of borrowing or selling to pay for health services among the poorest women. Taken together, insurance coverage may serve as an important policy tool in promoting NCD treatment and in reducing inequities in NCD treatment by household wealth, urbanicity, and sex in LMICs. PMID- 26271140 TI - Inhibition of tumor energy pathways for targeted esophagus cancer therapy. AB - Interest in targeting cancer metabolism has been renewed in recent years with the discovery that many cancer related pathways have a profound effect on metabolism and that many tumors become dependent on specific metabolic processes. Accelerated glucose uptake during anaerobic glycolysis and loss of regulation between glycolytic metabolism and respiration, are the major metabolic changes found in malignant cells. The non-metabolizable glucose analog, 2-deoxy-D-glucose inhibits glucose synthesis and adenosine triphosphate production. The adenosine monophosphate-activated protein kinase (AMPK) is a key sensor of cellular energy and AMPK is a potential target for cancer prevention and/or treatment. Metformin is an activator of AMPK which inhibits protein synthesis and gluconeogenesis during cellular stress. This article reviews the status of clinical and laboratory researches exploring targeted therapies via metabolic pathways for treatment of esophageal cancer. PMID- 26271141 TI - Effect of golimumab and pamidronate on clinical efficacy and MRI inflammation in axial spondyloarthritis: a 48-week open randomized trial. AB - OBJECTIVES: To compare the effect of golimumab (GLM) and pamidronate (PAM) on clinical efficacy and magnetic resonance imaging (MRI) inflammation in axial spondyloarthritis (aSpA). METHOD: Patients who fulfilled the Assessment of SpondyloArthritis Society (ASAS) criteria for aSpA and had active disease [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score >= 4] were randomized in a 2:1 ratio to receive either GLM (50 mg) or PAM (60 mg) 4 weekly for 48 weeks. Clinical efficacy was assessed at intervals. Inflammation of the spine and sacroiliac joints (SIJs) on MRI was graded by the Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system. RESULTS: Twenty patients were assigned to GLM and 10 to PAM (83% men; age 33.4 +/- 10.9 years; disease duration 4.4 +/- 3.4 years). The baseline characteristics of the two groups were similar. At week 48, the proportions of patients who achieved an ASAS20 response were not significantly different between the GLM and PAM groups (65% vs. 56%; p = 0.69). Although there were no differences in BASDAI, spinal pain, and Medical Outcomes Study 36-item Short Form Health Survey (SF-36) scores between the two groups at week 48, the Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath AS Functional Index (BASFI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels were significantly lower in GLM-treated patients. The SPARCC scores of the spine and SIJs decreased significantly in GLM- but not in PAM-treated patients. The differences in SPARCC scores between the two groups at week 48 were statistically significant. The frequency of adverse events (AEs) was similar in both arms. CONCLUSIONS: In patients with aSpA, the clinical response rate and improvement in pain and quality of life (QoL) were similar between GLM and PAM groups after 48 weeks. However, significant reduction in inflammatory markers and MRI inflammation was only observed with GLM treatment. PMID- 26271142 TI - Diversity of Mycobacterium tuberculosis lineages in French Polynesia. AB - BACKGROUND/PURPOSE: French Polynesia is an overseas territory located in the South Pacific. The incidence of tuberculosis in French Polynesia has been stable since 2000 with an average of 20 cases/y/100,000 inhabitants. Molecular epidemiology of Mycobacterium tuberculosis in French Polynesia is unknown because M. tuberculosis isolates have not been routinely genotyped. METHODS: From 2009 to 2012, 34 isolates collected from 32 French Polynesian patients were identified as M. tuberculosis by probe hybridization. These isolates were genotyped using spoligotyping and 24-loci mycobacterial interspersed repetitive units (MIRUs) variable number of tandem repeat (VNTR). Spoligotype patterns obtained using commercial kits were compared with the online international database SITVIT. MIRU VNTR genotyping was performed using an in-house protocol based on capillary electrophoresis sizing for 24-loci MIRU-VNTR genotyping. RESULTS: The results of the spoligotyping method revealed that 25 isolates grouped into six previously described spoligotypes [H1, H3, U likely (S), T1, Manu, and Beijing] and nine isolates grouped into six new spoligotypes. Comparison with the international database MIRU-VNTRplus distributed 30 isolates into five lineages (Haarlem, Latin American Mediterranean, S, X, and Beijing) and four as unassigned isolates. CONCLUSION: Genotyping identified four phylogenetic lineages belonging to the modern Euro-American subgroup, one Beijing genotype responsible for worldwide pandemics, including remote islands in the South Pacific, and one Manu genotype of the ancestral lineage of M. tuberculosis. PMID- 26271143 TI - Regulation of brown fat by AMP-activated protein kinase. AB - Novel strategies are needed to reduce the obesity epidemic. One promising strategy is activation of brown adipose tissue (BAT), either via the brain or directly, which increases energy expenditure by combustion of fatty acids (FAs) into heat. The enzyme complex AMP-activated protein kinase (AMPK) is crucially involved in energy metabolism and is highly expressed in both brain and BAT, regulating thermogenesis. As a general rule, BAT activity and energy expenditure are increased either by suppression of AMPK activity in the brain, resulting in enhanced sympathetic outflow towards BAT, or by activation of AMPK in BAT. Targeting AMPK may thus hold therapeutic potential for the treatment of obesity and related disorders. PMID- 26271144 TI - Clinical and prognostic relevance of EZH2 in breast cancer: A meta-analysis. AB - The polycomb group protein enhancer of zeste homolog 2 (EZH2) is regarded as a tightly linking oncogene in many types of cancer. However, the prognostic role of EZH2 in breast cancer (BC) still remains controversial. Our study aimed to evaluate the clinical and prognostic relevance of EZH2 in BC patients based on published studies. 11 studies totally containing 2330 patients (1052 EZH2 positive and 1278 EZH2-negative) were included in our meta-analysis. Our data showed that EZH2 over-expression was significantly associated with estrogen receptor (ER) negativity [OR=0.227, 95% CI=0.174-0.297, P=0.000], progesterone receptor (PR) negativity [OR=0.454, 95% CI=0.300-0.687, P=0.000], human epidermal growth factor receptor type 2 (HER-2) positivity [OR=1.846, 95% CI=1.366-2.496, P=0.000], invasive ductal cancer (IDC) [OR=2.237, 95% CI=1.489-3.361, P=0.000], race (Caucasian) [OR=0.707, 95% CI=0.522-0.957, P=0.025], high histological grade [OR=3.177, 95% CI=2.012-5.014, P=0.000] and triple-negative status (TNBCs) [OR=5.380, 95% CI=1.065-27.187, P=0.042], which led to a poor OS rate in BC [RR=2.193, 95% CI=1.495-3.217, P=0.000]. In conclusion, EZH2 participated in the progression of BC as a putative factor, and over-expression of EZH2 was distinctly correlated with a poor patient survival. EZH2 may serve as a prognostic biomarker and target in BC patients. PMID- 26271145 TI - Acute Kidney Disease Due to Excessive Vitamin C Ingestion and Remote Roux-en-Y Gastric Bypass Surgery Superimposed on CKD. AB - A 69-year-old woman presented with acute kidney failure of unknown cause that ultimately required dialysis. Kidney biopsy revealed the diagnosis of oxalate nephropathy. In retrospect, the patient had several risk factors for this entity, including excessive vitamin C intake, a remote history of Roux-en-Y gastric bypass for weight loss, and chronic kidney disease. This presentation of multiple risk factors for oxalate nephropathy is especially relevant to patients and physicians considering the increase in the United States of vitamin C supplementation use and gastric bypass surgery. It is important for physicians to maintain an awareness of this diagnosis and its risk factors. PMID- 26271147 TI - Imaging findings of fallopian tube leiomyoma with myxoid degeneration: a case report. AB - Leiomyomas from the fallopian tube are very rare and usually asymptomatic but may cause symptoms by torsion or obstruction. Herein, we describe the detailed imaging findings of tubal leiomyoma with myxoid degeneration. Tubal leiomyoma appeared as a well-defined juxtauterine tumor marginated by low-signal rims with intervening bridging vessels between the tumor and uterus. A tubal mass showing heterogeneous speckled high signals with intermediate signal background on T2 weighted image without diffusion restriction could suggest the probability of tubal leiomyoma with mxoid degeneration. PMID- 26271146 TI - Remote ischemic preconditioning for kidney protection: GSK3beta-centric insights into the mechanism of action. AB - Preventing acute kidney injury (AKI) in high-risk patients following medical interventions is a paramount challenge for clinical practice. Recent data from animal experiments and clinical trials indicate that remote ischemic preconditioning, represented by limb ischemic preconditioning, confers a protective action on the kidney. Ischemic preconditioning is effective in reducing the risk for AKI following cardiovascular interventions and the use of iodinated radiocontrast media. Nevertheless, the underlying mechanisms for this protective effect are elusive. A protective signal is conveyed from the remote site undergoing ischemic preconditioning, such as the limb, to target organs, such as the kidney, by multiple potential communication pathways, which may involve humoral, neuronal, and systemic mechanisms. Diverse transmitting pathways trigger a variety of signaling cascades, including the reperfusion injury salvage kinase and survivor activating factor enhancement pathways, all of which converge on glycogen synthase kinase 3beta (GSK3beta). Inhibition of GSK3beta subsequent to ischemic preconditioning reinforces the Nrf2-mediated antioxidant defense, diminishes the nuclear factor-kappaB-dependent proinflammatory response, and exerts prosurvival effects ensuing from the desensitized mitochondria permeability transition. Thus, therapeutic targeting of GSK3beta by ischemic preconditioning or by pharmacologic preconditioning with existing US Food and Drug Administration-approved drugs having GSK3beta-inhibitory activities might represent a pragmatic and cost-effective adjuvant strategy for kidney protection and prophylaxis against AKI. PMID- 26271148 TI - The computed tomographic angiography finding of hepatic artery dissection after living donor liver transplantation; what is the clinical significance? AB - OBJECTIVE: To correlate computed tomography (CT) findings of hepatic artery dissection (HAD) to clinical manifestations of arterial insufficiency and biliary stricture after living donor liver transplantation (LDLT). METHODS: Among 737 consecutive patients, we retrospectively reviewed incidence, CT findings, and complications of the HAD. RESULTS: HADs occurred in 43 patients, exclusively in recipient arteries. Most were resolved with recovery of true lumen without specific treatment. Five patients had insignificant hepatic arterial infarctions, and incidence of biliary stricture did not significantly differ with control group. CONCLUSIONS: HADs frequently occurred shortly after LDLT. Most HADs spontaneously improved and did not affect incidence of late biliary stricture. PMID- 26271149 TI - Extragastrointestinal stromal tumor of lesser omentum: a challenging radiological and histological diagnosis. AB - Extragastrointestinal stromal tumors (EGISTs) are a rare subgroup of gastrointestinal stromal tumors (GISTs), arising from outside the walls of gastrointestinal tubular organs. We report a case of an EGIST of the lesser omentum that represented a diagnostic challenge. Due to its atypical radiologic findings, it was preoperatively mistaken for pedunculated hepatic hemangioma. Histopathologically, it showed epithelioid structure and c-kit negative, very uncommon for GIST. Only a few cases of EGISTs have been previously reported. We discuss imaging and histological features, emphasizing potential pitfalls. PMID- 26271150 TI - Genomic organization of a novel victorivirus from the rice blast fungus Magnaporthe oryzae. AB - Two double-stranded RNA (dsRNA) mycoviruses were found in isolate QSP5 of the rice blast fungus Magnaporthe oryzae. Sequence analysis of the two dsRNA mycoviruses revealed that one is closely related to Magnaporthe oryzae virus 2 (MoV2), and the other one is related to Magnaporthe oryzae chrysovirus 1-A (MoCV1 A). Therefore, they were named Magnaporthe oryzae virus 3 (MoV3) and Magnaporthe oryzae chrysovirus 1-C (MoCV1-C), respectively. In this paper, the molecular and structural characteristics of MoV3 were analyzed in detail. The full genome sequence (5181 bp) of MoV3 was obtained by cDNA cloning. Sequence analysis indicated that MoV3 has two overlapping open reading frames (ORF1 and ORF2). The 5'-proximal ORF1 encodes a putative coat protein (CP) with a molecular weight of 80,939 Da; the 3'-proximal ORF2 encodes a putative RNA-dependent RNA polymerase (RdRp) with a molecular weight of 90,506 Da. The stop codon of ORF1 overlaps the start codon of ORF2, with the tetranucleotide sequence AUGA, which is characteristic of members of the genus Victorivirus of the family Totiviridae. Phylogenetic analysis of RdRp and CP further supported the view that MoV3, a novel mycovirus, belongs to the genus Victorivirus of the family Totiviridae. PMID- 26271151 TI - Complete genome analysis of equine coronavirus isolated in Japan. AB - Equine coronavirus has been responsible for several outbreaks of disease in the United States and Japan. Only one complete genome sequence (NC99 isolated in the US) had been reported for this pathogenic RNA virus. Here, we report the complete genome sequences of three equine coronaviruses isolated in 2009 and 2012 in Japan. The genome sequences of Tokachi09, Obihiro12-1 and Obihiro12-2 were 30,782, 30,916 and 30,916 nucleotides in length, respectively, excluding the 3' poly (A) tails. All three isolates were genetically similar to NC99 (98.2-98.7%), but deletions and insertions were observed in the genes nsp3 of ORF1a, NS2 and p4.7. PMID- 26271152 TI - A porcine circovirus-2 mutant isolated in Brazil contains low-frequency substitutions in regions of immunoprotective epitopes in the capsid protein. AB - Porcine circovirus-2 (PCV2) is the etiologic agent of several diseases in pigs, including multi-systemic wasting syndrome (PMWS). In this work, a new mutant PCV2b was isolated from PMWS-affected pigs on a Brazilian farm. Its genome showed high sequence similarity (>99% identity) to those from a group of emerging mutants isolated from cases of PMWS outbreaks in vaccinated pigs in China, the USA and South Korea. Here, we show that these isolates share a combination of low frequency substitutions (single amino acid polymorphisms with a frequency of <=25%) in the viral capsid protein, mainly in regions of immunoprotective epitopes, and an additional lysine residue at position 234. These isolates were phylogenetically grouped in the PCV2b clade, reinforcing the idea of the emergence of a new group of mutants PCV2b associated with outbreaks worldwide. The identification of these polymorphisms in the viral capsid highlights the importance of considering these isolates for the development of more-effective vaccines. PMID- 26271153 TI - Effect of truncation of the N-terminal region of the viral hemorrhagic septicemia virus (VHSV) P protein on viral replication. AB - The phosphoprotein (P) of viral hemorrhagic septicemia virus (VHSV) plays an essential role in viral replication by interconnecting the L protein and the N protein-RNA complex. In this study, to investigate the role of the N-terminal region of the P protein in viral replication, we mutated the first or the first and second or the first, second, and third ATG codon into TGA stop codons. The respective mutants were named P1, P2, and P3. Recombinant VHSVs containing each mutated P gene (rVHSV-P1, -P2, and -P3) were successfully generated by supplying the intact P protein in trans. The rVHSV-P2 and -P3 were not generated from cells expressing truncated P proteins (P1, P2 or P3 protein), but the rVHSV-P1 produced infectious viruses, even in cells without any P-protein-expressing plasmids. Nucleotide sequence analysis of the P gene of rVHSV-P1 showed that a mutation had occurred that resulted in the fourth amino acid (isoleucine, ATT) being changed to methionine (ATG) without a frameshift (P0.5), suggesting that strong selection pressure might facilitate mutations that are advantageous or essential for virus replication. Infectious rVHSV-P2 and -P3 were produced in cells expressing the P0.5 protein, suggesting that the first three amino acids of the P protein of VHSV are dispensable for viral replication. Furthermore, although the P1 protein was shorter than the P0.5 protein by only two amino acid residues, no viruses were produced when the P1 protein was supplied indicating that the fourth and the fifth amino acid residues are indispensable for normal P protein functions involved in viral replication. PMID- 26271154 TI - Galvanic Vestibular Stimulation Induces a Spatial Bias in Whole-body Position Estimates. PMID- 26271155 TI - Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer. AB - OBJECTIVE: OCEANS is a randomized, placebo (PL)-controlled, phase 3 trial evaluating the efficacy and safety of bevacizumab combined with gemcitabine+carboplatin (GC) for patients with platinum-sensitive recurrent ovarian cancer (ROC). The study met its primary endpoint, demonstrating improved progression-free survival with GC+bevacizumab compared with GC+PL. Herein, we describe results of final overall survival (OS) and updated safety. METHODS: Patients with recurrent platinum-sensitive ROC (recurring >=6months after first line platinum-based therapy) and measurable disease at baseline were randomized to receive GC+bevacizumab or GC+PL for 6-10cycles; PL or bevacizumab was then continued until disease progression. In this updated analysis, a Cox proportional hazards model was used to compare OS between the 2 treatment arms. RESULTS: At the data cutoff date (July 19, 2013), 353 patients (72.9%) had died. Median follow-up for OS was 58.2months in the experimental arm and 56.4months in the control arm. Consistent with interim analyses, median OS was comparable between arms (GC+bevacizumab: 33.6months; GC+PL: 32.9months; hazard ratio=0.95; log-rank p=0.65), and was consistent across all examined patient subgroups. The frequency and severity of adverse events were consistent with previous analyses; no new safety concerns were identified. CONCLUSIONS: Results from final OS analysis of the phase 3 OCEANS study showed no significant difference in OS for patients treated with GC+bevacizumab compared with GC+PL. PMID- 26271156 TI - Candidate biomarkers for mosquito age-grading identified by label-free quantitative analysis of protein expression in Aedes albopictus females. AB - We applied a "shotgun" approach based on nanoliquid chromatography-high resolution mass spectrometry associated to label free quantification (LFQ) to identify proteins varying with age, independently from the physiological state, in Aedes albopictus, a mosquito species which in the last decades invaded temperate regions in North America and Europe, creating concerns for associated high nuisance and risk of arbovirus transmission. The combined "shotgun" and LFQ approach was shown to be highly suitable to simultaneously compare several biological samples, as needed in a study aimed to analyze different age-groups and physiological states of adult mosquito females. The results obtained represent the first wide-scale analysis of protein expression in Ae. albopictus females: >1000 and 665 proteins were identified from few micrograms of crude protein extracts of mosquito heads and thoraxes, respectively. Six of these proteins were shown to significantly vary from 2- to 16-day-old females, independently from their physiological state (i.e. virgin, mated, host-seeking, blood-fed, and gravid). BIOLOGICAL SIGNIFICANCE: Mosquito-borne diseases, such as malaria, dengue and other arboviroses, are a persistent cause of global mortality and morbidity, affecting hundreds of thousands of people. Billions of people living in tropical areas are at risk of being bitten every day by an infective mosquito female and the spread of tropical species such as Aedes albopictus to temperate areas is creating alarm in the northern hemisphere. Mosquito longevity is a critical factor affecting mosquito-borne pathogen transmission cycles and the mosquito capacity to transmit pathogens. However, large scale analyses of the age structure of mosquito field populations is hampered by the lack of optimal age-grading approaches. Our findings open new perspectives for the development of reliable, simple and cheap protein-based assays to age-grade Ae. albopictus females and, most likely, other mosquito species of higher medical relevance, such as the main dengue vector, Aedes aegypti, and the major Afrotropical malaria vectors. These assays would greatly contribute to epidemiological studies aimed at defining the actual vectorial capacity of a given mosquito species. Moreover, they would be very valuable in assessing the effectiveness of mosquito control interventions based on the relative ratio between young and old individuals before and after the intervention. PMID- 26271158 TI - Aldur W. Eriksson 7.1.1927-3.4.2015. PMID- 26271159 TI - Preparation of size-selective Mn3O4 hexagonal nanoplates with superior electrochemical properties for pseudocapacitors. AB - Porous Mn3O4 hexagonal nanoplates were synthesized through annealing the hydrohausmannite precursor obtained by a one-pot hydrothermal process and by precisely controlling the concentrations of potassium hydroxide and glucose. The effect of potassium hydroxide and glucose on the growth of hexagonal nanoplates was investigated, and a growth mechanism was also proposed. Due to its abundant pores, the pure Mn3O4-based electrode exhibits excellent cycling stability with 100% capacity retention after 5000 cycles. The asymmetric supercapacitor exhibited high performance with an energy density of 17.276 W h kg(-1) at a power density of 207.3 W kg(-1) in a wide potential window of 1.5 V. PMID- 26271157 TI - Proteome analysis of the triton-insoluble erythrocyte membrane skeleton. AB - Erythrocyte shape and membrane integrity is imparted by the membrane skeleton, which can be isolated as a Triton X-100 insoluble structure that retains the biconcave shape of intact erythrocytes, indicating isolation of essentially intact membrane skeletons. These erythrocyte "Triton Skeletons" have been studied morphologically and biochemically, but unbiased proteome analysis of this substructure of the membrane has not been reported. In this study, different extraction buffers and in-depth proteome analyses were used to more fully define the protein composition of this functionally critical macromolecular complex. As expected, the major, well-characterized membrane skeleton proteins and their associated membrane anchors were recovered in good yield. But surprisingly, a substantial number of additional proteins that are not considered in erythrocyte membrane skeleton models were recovered in high yields, including myosin-9, lipid raft proteins (stomatin, flotillin1 and 2), multiple chaperone proteins (HSPs, protein disulfide isomerase and calnexin), and several other proteins. These results show that the membrane skeleton is substantially more complex than previous biochemical studies indicated, and it apparently has localized regions with unique protein compositions and functions. This comprehensive catalog of the membrane skeleton should lead to new insights into erythrocyte membrane biology and pathogenic mutations that perturb membrane stability. Biological significance Current models of erythrocyte membranes describe fairly simple homogenous structures that are incomplete. Proteome analysis of the erythrocyte membrane skeleton shows that it is quite complex and includes a substantial number of proteins whose roles and locations in the membrane are not well defined. Further elucidation of interactions involving these proteins and definition of microdomains in the membrane that contain these proteins should yield novel insights into how the membrane skeleton produces the normal biconcave erythrocyte shape and how it is perturbed in pathological conditions that destabilize the membrane. PMID- 26271160 TI - Smoking-Related Beliefs and Susceptibility Among United States Youth Nonsmokers. AB - PURPOSE: The purpose of the study was to examine racial/ethnic disparities in smoking beliefs and susceptibility in a nationally representative sample of United States youth nonsmokers (N = 21,931). METHODS: Weighted regression models were used to examine smoking-related beliefs and susceptibility by race/ethnicity adjusting for demographics, exposure to pro-tobacco advertising and promotions, parental guidance against tobacco use, and peer norms. RESULTS: Compared with non Hispanic whites, racial/ethnic minority youth endorsed pro-smoking beliefs and were susceptible to smoking. Non-Hispanic blacks, non-Hispanic Asians, and Hispanics embraced social benefits of smoking (all p < .05). Hispanics had lower perceptions of tobacco-related risks (adjusted odds ratio = .87) and were more susceptible to smoking (adjusted odds ratio = 1.56). Disparities in smoking beliefs and susceptibility persisted between minority and non-Hispanic white youth after adjusting for exposure to pro-tobacco advertising and promotions, parental guidance against tobacco use, and peer norms. CONCLUSIONS: Smoking related beliefs and susceptibility varied by race/ethnicity among youth nonsmokers after accounting for known predictors of youth smoking. PMID- 26271161 TI - Teen Dating Violence Victimization and Patterns of Substance Use Among High School Students. AB - PURPOSE: Substance use in adolescence is a significant concern, particularly the use of multiple drugs. Yet, most studies examine a single substance in isolation, with limited consideration of the use of multiple substances. Furthermore, few studies have examined how teen dating violence (TDV) victimization is associated with patterns of substance use. METHODS: Using latent class analysis and latent class regression, the present study aimed to (1) identify subtypes of substance use among high school students and (2) examine the association between past-year physical and psychological TDV victimization and pattern of substance use. We focused on 30-day use of alcohol, binge drinking, marijuana, cigarette, cigarillo, and prescription drug use. Analyses were conducted on data from 18,680 adolescents in Grades 9-12, across 58 high schools. RESULTS: The latent class analysis indicated a five-class model best fit the data; the largest class was composed of nonusers, whereas the other classes were high polysubstance use, alcohol use, alcohol and marijuana use, and moderate polysubstance use. The multinomial regression analyses indicated that adolescents who had experienced physical and psychological TDV were more likely to be in the two polysubstance use classes and the alcohol and marijuana use class, as compared with nonvictimized adolescents. CONCLUSION: There is heterogeneity in adolescents' self-reported recent substance use, although a large proportion of substance using youth reported recent alcohol and marijuana use. Preventive interventions should focus their efforts on preventing substance use among victims of TDV, in part because substance use is a risk factor for TDV victimization. PMID- 26271163 TI - Tailoring mechanical response through coronal layer overlap in tethered micelle hydrogel networks. AB - Tethered micelle hydrogel networks based on the solution assembly of amphiphilic ABA-type block copolymers are prevalent throughout the hydrogel literature. However, the mechanical response of such systems is often determined largely by the integrity of the micellar core produced during solution assembly, not by the elements of the network structure upon which it is based. Using a solvent-free fabrication method based on the melt-state self-assembly of sphere-forming polystyrene-b-poly(ethylene oxide) (SO) diblock and SOS triblock copolymers blends, we have been able to produce tethered micelle hydrogel networks with fully vitrified cores that enable the elements of the network structure to determine the mechanical response. Here, we explore the impact of using PEO midblocks of different lengths within the SOS tethers, in an effort to elucidate the role played by water content, tether concentration, and tether length in mechanical property determination. In doing so, we were able to establish coronal layer overlap as the primary contributing factor in regulating the dynamic elastic moduli exhibited by tethered micelle systems. Variation of either tether concentration or tether length could be used to tune the degree of coronal layer overlap, enabling direct and accurate control over hydrogel mechanical response. While such control is likely a unique feature of the melt-state fabrication approach applied here, the conclusions with respect to the role of coronal layer overlap and tether (bridging) concentration in determining the mechanical potential of the network should be applicable to all ABA-type tethered micelle systems, regardless of fabrication methodology. PMID- 26271162 TI - Do Savings Mediate Changes in Adolescents' Future Orientation and Health-Related Outcomes? Findings From Randomized Experiment in Uganda. AB - PURPOSE: This present study tests the proposition that an economic strengthening intervention for families caring for AIDS-orphaned adolescents would positively affect adolescent future orientation and psychosocial outcomes through increased asset accumulation (in this case, by increasing family savings). METHODS: Using longitudinal data from the cluster-randomized experiment, we ran generalized estimating equation models with robust standard errors clustering on individual observations. To examine whether family savings mediate the effect of the intervention on adolescents' future orientation and psychosocial outcomes, analyses were conducted in three steps: (1) testing the effect of intervention on mediator; (2) testing the effect of mediator on outcomes, controlling for the intervention; and (3) testing the significance of mediating effect using Sobel Goodman method. Asymmetric confidence intervals for mediated effect were obtained through bootstrapping-to address the assumption of normal distribution. RESULTS: Results indicate that participation in a matched Child Savings Account (CSA) program improved adolescents' future orientation and psychosocial outcomes by reducing hopelessness, enhancing self-concept, and improving adolescents' confidence about their educational plans. However, the positive intervention effect on adolescent future orientation and psychosocial outcomes was not transmitted through saving. In other words, participation in the matched CSA program improved adolescent future orientation and psychosocial outcomes regardless of its impact on reported savings. CONCLUSIONS: Further research is necessary to understand exactly how participation in economic strengthening interventions, for example, those that employ matched CSAs, shape adolescent future orientation and psychosocial outcomes: what, if not savings, transmits the treatment effect and how? PMID- 26271164 TI - In vitro fertilization in pigs: New molecules and protocols to consider in the forthcoming years. AB - Assisted reproduction technology (ART) protocols are used in livestock for the improvement and preservation of their genetics and to enhance reproductive efficiency. In the case of pigs, the potential use of embryos for biomedicine is being followed with great interest by the scientific community. Owing to the physiological similarities with humans, embryos produced in vitro and many of those produced in vivo are used in research laboratories for the procurement of stem cells or the production of transgenic animals, sometimes with the purpose of using their organs for xenotransplantation. Several techniques are required for the production of an in vitro-derived embryo. These include in vitro oocyte maturation, sperm preparation, IVF, and further culture of the putative zygotes. Without doubt, among these technologies, IVF is still a critical limiting factor because of the well-known, but still unsolved, question of polyspermy. Despite the improvements made in the past decade, current IVF systems hardly reach 50% to 60% efficiency and any progression in porcine ARTs requires an unavoidable improvement in the monospermy rate. It is time, then, to learn from what happens under in vivo physiological conditions and to transfer this knowledge into ART. This review describes the latest advances in porcine IVF, from sperm preparation procedures to culture media supplements with special attention paid to molecules with a known or potential role in in vivo fertilization. Oviductal fluid is the natural medium in which fertilization takes place, and, in the near future, could become the definitive supplement for culture media, where it would help to solve many of the problems inherent in ARTs in swine and improve the quality of in vitro-derived porcine embryos. PMID- 26271166 TI - [Gastric volvulus in children]. AB - BACKGROUND: Gastric volvulus in children is rare and can be life-threatening if not recognised in time. CASE DESCRIPTION: A 3.5-year-old boy presented to his GP with severe, non-bilious vomiting, abdominal distension and abdominal pain. Additional diagnostic tests showed hypochloraemic alkalosis and abdominal ultrasonography suggested gastric volvulus. A barium study showed slow passage of contrast into the duodenum combined with craniomedial displacement of the duodenum. This image matches that of mesenteroaxial gastric volvulus. The diagnosis was confirmed during surgery and gastropexy was successfully performed. CONCLUSION: The diagnosis of gastric volvulus can be difficult. Easily accessible additional diagnostics in the form of ultrasonography, possibly followed by a barium study, may be helpful. PMID- 26271165 TI - Effect of the probiotic Lactobacillus rhamnosus on the expression of genes involved in European eel spermatogenesis. AB - Positive effects of probiotics on fish reproduction have been reported in several species. In the present study, 40 male European eels were weekly treated with recombinant hCG for 9 weeks and with three different concentrations (10(3), 10(5), and 10(6) CFU/mL) of probiotic Lactobacillus rhamnosus IMC 501 (Sinbyotec, Italy). The probiotics were daily added to the water from the sixth week of the hCG treatment. Males from the treated and control groups were sacrificed after 1, 2, and 3 weeks of probiotic treatment (seventh-ninth weeks of hCG treatment); at this point, sperm and testis samples were also collected. Sperm volume was estimated, and motility was analyzed by computer-assisted sperm analysis software. Alternations in transcription of specific genes involved in reproductive process such as activin, androgen receptors alpha and beta (aralpha and arbeta), progesterone receptor 1 (pr1), bone morphogenetic protein 15 (bmp15), and FSH receptor (fshr) were analyzed in the testis. After 2 weeks of probiotic treatment, sperm production and sperm motility parameters (percentage of motile cells and percentage of straight-swimming spermatozoa) were increased in the European eel treated with 10(5) CFU/mL compared to controls or to the other probiotic doses. These changes were associated with increases in messenger RNA expression of activin, aralpha, arbeta, pr1, and fshr. Conversely, after 3 weeks, activin and pr1 expression decreased. No significant changes were observed on bmp15 expression throughout the duration of the treatment with 10(5) CFU/mL dose. The lowest and highest probiotic dose (10(3) and 10(6) CFU/mL, respectively) inhibited the transcription of all genes along all the experiment, except for aralpha and arbeta after 1 week of probiotic treatment when compared to controls. The changes observed by transcriptomic analysis and the sperm parameters suggest that a treatment with L rhamnosus at 10(5) CFU/mL for 2 weeks could improve spermatogenesis process in Anguilla anguilla. PMID- 26271167 TI - [Dutch-language patient-reported outcome measures for foot and ankle injuries; a systematic review]. AB - OBJECTIVE: To investigate which valid and reliable patient-reported outcome measures (PROMs) are available for foot and ankle disorders in the Dutch population, and which of these is the most suitable for uniform use. DESIGN: Systematic review. METHOD: PubMed, Embase and Google Scholar were systematically searched for relevant articles; subsequently two researchers screened first the title and the abstract, and then the full article within a selection of these articles. Studies that described a validation process for foot- and ankle-PROMs in a Dutch population were included. Data on measurement characteristics and translation procedure were extracted, and methodological quality of the studies was assessed using the COSMIN checklist. ('COSMIN' stands for 'Consensus-based standards for the selection of health status measurement instruments'.) RESULTS: Two general foot- and ankle-PROMs in the Dutch language were validated: the Foot and Ankle Outcome Score (FAOS) and the Foot and Ankle Ability Measurement (FAAM); two foot-PROMs: the Manchester Foot Pain and Disability Index (MFPDI) and the 5 point Foot Function Index (FFI-5pt) were also validated. There were also two disorder-specific PROMs available in Dutch: the Victorian Institute of Sports Assessment-Achilles (VISA-A) for Achilles tendinopathies and the Foot Impact Scale for Rheumatoid Arthritis (FIS-RA) for rheumatoid arthritis patients. CONCLUSION: The FAOS and the FFI-5pt showed the strongest evidence for having good measurement characteristics. Currently, we regard the FAOS as the most appropriate foot- and ankle-PROM for general foot and ankle problems. Further studies of higher methodological quality are, however, required to draw firmer conclusions. PMID- 26271168 TI - [A man with vision problems after coronary angiography]. AB - A 71-year-old man underwent a coronary angiography (CAG). Afterwards he experienced vision loss. Neurologic examination revealed bilateral cortical blindness. A cerebral CT-scan showed occipital hyperdensity, due to contrast accumulation and oedema. There was complete recovery of vision within 2 days. Transient cortical blindness after CAG is a rare complication of iodinated contrast agents. PMID- 26271169 TI - [A supracondylar process in a child with arm pain]. AB - A 14-year-old boy had arm pain after a traumatic event. An X-ray showed a supracondylar process of the humerus, which is a coincidental finding but sometimes has clinical consequences. It may compress the median nerve or brachial artery, leading to symptoms. Resection can give complete relieve of symptoms. PMID- 26271170 TI - [Decision-making in preoperative radiotherapy in rectal cancer: variation in provision of information]. AB - OBJECTIVE: To investigate the information provision concerning possible benefits and harms of short-course preoperative radiotherapy (PRT) at pre-treatment consultations between radiation oncologists and rectal cancer patients. DESIGN: Observational study. METHOD: We audiotaped the consultations between 17 radiation oncologists and 81 patients with primary rectal cancer who were eligible for PRT. The recordings were transcribed and analysed descriptively. RESULTS: A median of seven benefits/harms of PRT were addressed at each consultation (range, 2-13). This number differed both in and between individual oncologists and was not consistently associated with the patient's characteristics. A total of 30 different treatment outcomes was addressed. The effect of PRT on local control was addressed in all consultations, and the effect on survival in 16%. The most important adverse effects according to the literature are bowel dysfunction and sexual dysfunction. These were addressed in 82% and 85% of consultations, respectively; sexual problems were discussed significantly more often with male than female patients. Four out of five patients did not initiate discussion on potential benefits/harms. CONCLUSION: There was a considerable variation in the number and nature of benefits and harms of PRT that were discussed prior to treatment. This variation indicates a lack of clarity concerning which benefits/harms of radiotherapy should be discussed with newly-diagnosed patients. This suboptimal provision of information to patients hampers the process of shared decision making, in which the decision is based on each individual patient's weighing of benefits and harms. We do not believe our findings to be specific for PRT, but expect to find similar variation in provision of information with regard to other treatment decisions. PMID- 26271171 TI - [Unravelling medical leadership]. AB - Medical leadership is a popular topic in the Netherlands, and several interest groups now incorporate medical leadership into postgraduate medical education. However, there is no consensus on what this concept entails. By conducting a discourse analysis, a qualitative method which uses language and text to reveal existing viewpoints, this article reveals three perspectives on medical leadership: administrative leadership, leadership within organisations and leadership within each doctor's daily practice. Text analysis shows that the first two perspectives refer to medical leadership mainly in a defensive manner: by demonstrating medical leadership doctors could 'take the lead' once again; patient care only seems to play a small part in the process. These perspectives are not free of consequences, they will determine how the medical profession is constructed. For this reason, it is argued that there should be more emphasis on the third perspective, in which the quality of care for patients is of primary importance. PMID- 26271172 TI - [Dose-reduction of TNF-alpha blockers in patients with rheumatoid arthritis]. AB - Tumour-necrosis-factor alpha (TNF-alpha) blockers are highly effective in patients with rheumatoid arthritis, but their use is limited by the high costs of the drug: around ? 10,000 to ? 15,000 per patient per year. In a recent randomised study, it was shown that dose reduction, or even stopping the medication, was possible in 43% and 20% of patients, respectively; the percentage of patients with a major flare was comparable: 10% versus 12%. Another study, in patients with rheumatoid arthritis in clinical remission, showed no difference in response between patients continuing etanercept 50 mg per week and patients in whom the dosage was reduced to 25 mg per week. These studies suggest that dose reduction is possible in a substantial number of patients with rheumatoid arthritis. It is not yet possible, however, to predict which individuals are at high risk for flares when reducing the dosage of TNF-alpha blocking agents. PMID- 26271173 TI - [Pneumococcal vaccine for pneumonia mostly unnecessary]. AB - The efficacy of 13-valent polysaccharide conjugate vaccine (PCV13) was studied in a randomised, placebo-controlled trial involving 84,496 adults aged >= 65 years of age. PCV13 was partly effective in preventing vaccine-type pneumococcal pneumonia, but not in preventing either community-acquired pneumonia from any cause or death. The limited added value for individuals and society calls for reflection rather than mass vaccination. Emphasis on adequate and timely diagnosis of pneumonia with appropriate, personalised management - combined with 'tender loving care', particularly for the frail elderly - is a better option than the ongoing, costly search for the ultimate vaccine to prevent pneumococcal pneumonia. PMID- 26271174 TI - [Serious infection due to biologicals: risk only mildly elevated in patients with rheumatoid arthritis]. AB - Biologicals are often thought to increase the risk of infection. A recent review shows that the risk of serious infection in patients with rheumatoid arthritis being treated with biologicals (standard dose) is only mildly elevated compared with those who are treated with conventional DMARDs only (odds ratio: 1.3). If biologicals are used at a lower dosage, e.g. tapering studies, the risk of serious infection does not seem to be increased. Alertness for infection in these patients, dose tapering and preventive measures such as vaccination, patient education and tuberculosis screening may potentially further reduce this serious side effect of biologicals. PMID- 26271175 TI - [Shared decision-making becoming increasingly important]. AB - The paper by Kunneman and colleagues published in the Dutch Journal of Medicine (NTvG) touches upon a timely and important health care issue: shared decision making. The study focused on the adequacy of the information given to patients by their treating radiation oncologists before undergoing preoperative radiotherapy for rectal cancer. The main conclusion of this study is that there is a wide variation in the quantity and quality of the information given regarding the advantages and disadvantages of this treatment. This commentary reviews the data presented and relates them to several ongoing national initiatives to improve information provision to patients and to stimulate shared decision-making. PMID- 26271176 TI - [Earlier case finding and immediate treatment of HIV: Time2Act]. AB - Recent studies show that HIV-infected persons who start directly with their anti retroviral therapy (ART) have better outcomes in terms of morbidity and mortality than those who wait till their CD4 count decreases. In the Netherlands 24-34% is unaware of their HIV infection and 43% present late, especially migrants. Implementing proactive early case-finding will benefit both individual wellbeing as well as public health, as ART will also reduce or eliminate onward transmission to partners. PMID- 26271177 TI - [Treatment of patients with Alzheimer's disease: a breakthrough or not?]. AB - The results of an open-label extension study of the Expedition I and II studies with solanezumab in patients with Alzheimer's disease, neither of which had shown an effect on cognition and functional ability, were recently presented at the Alzheimer's Association International Conference in Toronto. Placebo and intervention patients with mild Alzheimer's disease from both studies were offered the option of continuing with solanezumab for 2 additional years. The data from this group were re-analysed using a new analysis technique, the so called 'delayed start analysis'. On the basis of the re-analysis it was concluded that solanezumab does show disease-modifying activity and should be considered a promising candidate for treatment of Alzheimer's disease in the near future. This conclusion, however, is poorly supported by the data presented in the study. A more definite positioning of solanezumab will not be possible until data from the ongoing Expedition III study becomes available in 2017 at the earliest. PMID- 26271178 TI - Abdominal vasculature in dynamic contrast-enhanced liver MRI at 3.0T: an intraindividual comparative study using gadoxetate disodium and gadofosveset trisodium. AB - OBJECTIVES: To intraindividually compare gadoxetate disodium and gadofosveset trisodium regarding vessel contrast, image quality and vessel delineation in dynamic contrast-enhanced liver MRI at 3.0T. METHODS: Twelve patients underwent 3.0T MRI twice (24 examinations) with a single dose of gadoxetate disodium and gadofosveset trisodium, respectively. Signal intensity in abdominal vessels and tissue was determined. Vessel-to-background ratio (VBR) was calculated for each vessel and dynamic phase. All images were evaluated by two radiologists regarding image quality, vessel delineation and anatomic variants or pathologies with digital subtraction angiography as the standard of reference. RESULTS: Gadofosveset trisodium demonstrated a significantly higher VBR compared to gadoxetate disodium (arterial phase: 0.57+/-0.12 [SD] vs. 0.46+/-0.19; portal venous phase: 0.51+/-0.11 vs. 0.37+/-0.14; equilibrium phase: 0.48+/-0.10 vs. 0.31+/-0.13; p<=0.01). Image quality and vessel delineation were rated equal or better for gadofosveset trisodium in all cases. These differences were not significant for most vessel segments. All anatomic variants were correctly identified by both readers for both contrast agents. CONCLUSIONS: Although gadofosveset trisodium provides a significantly higher vessel contrast at 3.0T, gadoxetate disodium is equivalent by qualitative measurements. Thus, gadoxetate enhanced liver MRI at 3.0T enables reliable assessment of the upper abdominal vasculature with the additional benefit of hepatobiliary imaging. PMID- 26271179 TI - Introduction and empirical assessment of executive functioning as a predictor of job performance. AB - The primary purposes of this study were (a) to introduce the concept of executive functioning (higher-level cognitive processes which monitor events, actions, and outcomes) to the employee selection literature and (b) to provide an empirical assessment of executive functioning in relation to key selection variables. Two of the three main components of executive functioning (set shifting and inhibition) appear to have considerable potential for selection because of their unique nature (e.g., self-directed, goal-oriented) and because they appear to be only modestly associated with general mental ability. While our empirical results were inconsistent, there may be underlying reasons for this, such as the unstable nature of the retail job sector. We believe there is considerable justification for continued exploration of this unique and potentially promising construct, and identify a number of directions for future research. PMID- 26271180 TI - Excelling at selling: The charming personality style predicts occupational activities, sales performance, and persuasive competence. AB - The present research investigates how individual differences in charming personality are related to occupational activities, sales performance, and persuasive competence. Study 1 showed that sales representatives had higher scores on the charming personality style than executive managers. Study 2 showed that the charming personality style predicted actual sales performance among branch managers of a large German insurance company over a period of 2 years; the explicit power motivation served as a mediator in this relation. Finally, Study 3, carried out in a laboratory setting, confirmed the hypothesis that a charming personality is associated with persuasive competence, which suggests that this style is more relevant for sales representatives than for executive managers. The authors conclude that the charming personality style represents an important psychological resource for organizations. PMID- 26271182 TI - National narcissism: Internal dimensions and international correlates. AB - In studies conducted in the United States and China, we explored the impact of national narcissism, grandiosity, and entitlement, demonstrating that: (a) national narcissism was distinct from both individual narcissism and collective self-esteem (patriotism); (b) national entitlement and national grandiosity constituted two distinct dimensions of national narcissism; and (c) national narcissism, national grandiosity, and national entitlement, but not individual narcissism, were uniquely predictive of political attitudes, foreign policy preferences, and purchase intentions. Together, these findings provided convergent evidence for the utility of national narcissism and its two internal dimensions, national entitlement and national grandiosity. PMID- 26271181 TI - The relation between prospective memory and working memory: Evidence from event related potential data. AB - Event-related potentials were used in this study to investigate the neural correlates of prospective memory and whether working memory is involved in prospective remembering. Thirty undergraduate or graduate students participated in the study. All participants completed a working memory test, namely, the Chinese Letter-Number Span Test, and were divided into two groups: the longer and shorter working memory span groups. They also undertook a prospective memory task while electrophysiological data were recorded. The results showed that participants in the longer working memory span group had shorter reaction times and smaller amplitudes in prospective positivity than participants in the shorter working memory span group. The results suggested that working memory resources are involved in the intention retrieval process of prospective remembering. PMID- 26271183 TI - Chinese school teachers' organizational citizenship behavior (OCB): Predictors and outcomes. AB - Teacher's organizational citizenship behavior (OCB) is a multifaceted construct that is critical to school effectiveness and to the education enterprise. Four hundred ninety-three teachers in eight different cities on the Chinese mainland were surveyed using the OCB scale developed by Bo Shiuan Cheng, a Taiwanese scholar. The antecedent and outcome variables of OCB were examined in this study. The results showed that the teachers' attitudinal characteristics of career satisfaction and career commitment, and the dispositional characteristic of locus of control, influenced teachers' OCB. In addition, teachers' OCB influenced their work performance as well as their career and organizational turnover intention. The implications of this study suggest a base of knowledge from which school administrators could enhance their school's organizational function and retain teachers. PMID- 26271185 TI - Endoluminal stenting via the suture-assisted flange engagement technique. PMID- 26271186 TI - Variability in microRNA recovery from plasma: Comparison of five commercial kits. AB - Numerous studies have indicated that microRNAs (miRNAs) are present and stable in multiple biological fluids, suggesting a great potential as biomarkers for molecular diagnostics and prognostics. Variations in the amount of starting material and isolation method to obtain miRNA may introduce bias and contribute to quantification errors. Given these concerns, we compared five commercially available kits for serum/plasma miRNA isolation to determine whether the plasma miRNA profile varies with the isolation method. We isolated miRNAs in blood plasma from colorectal cancer patients and healthy donors with five commercially available kits: Exiqon, Norgen, Macherey-Nagel, Qiagen, and Zymo Research. First, we assessed the robustness of the RNA isolation process and the quality of isolated miRNAs with the miRCURY microRNA QC PCR Panel (Exiqon), which contains six RNA spike-ins for quality control of RNA isolation (UniSp2, -4, and -5), complementary DNA (cDNA) synthesis (UniSp6 and cel-miR-39-3p), and polymerase chain reaction (PCR) amplification (UniSp3). This panel also includes circulating human miR-103, miR-191, miR-23a, and miR-451. Second, to evaluate the variability in miRNA profiling in relation to the extraction method, we analyzed plasma levels of candidate miRNA biomarkers for colorectal cancer (miR-18a, miR-21, and miR-29a). To determine PCR efficiencies per amplicon and per sample, we used LinRegPCR software. We found that all isolation methods were suitable for extracting miRNA from plasma samples and that all had similar Cq values in the three steps analyzed: RNA isolation, cDNA synthesis, and quantitative reverse transcription (qRT)-PCR. However, although the PCR replicates were excellent, the intersample variability of the spike-ins was unsatisfactorily high and all kits yielded suboptimal PCR efficiencies for some amplicons. Overall, our results underline the great difficulties involved in measuring miRNAs in plasma. The use of spike-ins is critical to control technical factors that affect final miRNA levels. We recommend that researchers investigating circulating miRNAs verify the PCR efficiency for each amplicon because quantification may be influenced by sample and PCR components. PMID- 26271187 TI - Cu(I)-NHC-Catalyzed (2 + 3)-Annulation of Tetramic Acids with 2H-Azirines: Stereoselective Synthesis of Functionalized Hexahydropyrrolo[3,4-b]pyrroles. AB - A stereoselective and high-yield synthesis of hexahydropyrrolo[3,4-b]pyrroles from tetramic acids and 2H-azirines under Cu(I)-NHC catalysis is developed. An unusual N-C2 azirine bond cleavage, initiated by a copper enolate, was rationalized in terms of a free radical reaction mechanism. PMID- 26271184 TI - Gastrointestinal traits: individualizing therapy for obesity with drugs and devices. AB - BACKGROUND AND AIMS: The aims of this article were to review the discrepancy between numbers of people requiring weight loss treatment and results and to assess the potential effects of pharmacologic treatments (recently approved for obesity) and endoscopically deployed devices on quantitative GI traits in development for obesity treatment. METHODS: We conducted a review of relevant literature to achieve our objectives. RESULTS: The 2013 guidelines increased the number of adults recommended for weight loss treatment by 20.9% (116.0 million to 140.2 million). There is an imbalance between efficacy and costs of commercial weight loss programs and drug therapy (average weight loss about 5 kg). The number of bariatric procedures performed in the United States has doubled in the past decade. The efficacy of bariatric surgery is attributed to reduction in the volume of the stomach, nutrient malabsorption with some types of surgery, increased postprandial incretin responses, and activation of farnesoid X receptor mechanisms. These GI and behavioral traits identify sub-phenotypes of obesity, based on recent research. CONCLUSIONS: The mechanisms or traits targeted by drug and device treatments include centrally mediated alterations of appetite or satiation, diversion of nutrients, and alteration of stomach capacity, gastric emptying, or incretin hormones. Future treatment may be individualized based on quantitative GI and behavioral traits measured in obese patients. PMID- 26271188 TI - Metabolically healthy and unhealthy obesity: differential effects on myocardial function according to metabolic syndrome, rather than obesity. AB - BACKGROUND: The term 'metabolically healthy obese (MHO)' is distinguished using body mass index (BMI), yet BMI is a poor index of adiposity. Some epidemiological data suggest that MHO carries a lower risk of cardiovascular disease (CVD) or mortality than being normal weight yet metabolically unhealthy. OBJECTIVES: We aimed to undertake a detailed phenotyping of individuals with MHO by using imaging techniques to examine ectopic fat (visceral and liver fat deposition) and myocardial function. We hypothesised that metabolically unhealthy individuals (irrespective of BMI) would have adverse levels of ectopic fat and myocardial dysfunction compared with MHO individuals. SUBJECTS: Individuals were categorised as non-obese or obese (BMI ?30 kg m(-2)) and as metabolically healthy or unhealthy according to the presence or absence of metabolic syndrome. METHODS: Sixty-seven individuals (mean+/-s.d.: age 49+/-11 years) underwent measurement of (i) visceral, subcutaneous and liver fat using magnetic resonance imaging and proton magnetic resonance spectroscopy, (ii) components of metabolic syndrome, (iii) cardiorespiratory fitness and (iv) indices of systolic and diastolic function using tissue Doppler echocardiography. RESULTS: Cardiorespiratory fitness was similar between all groups; abdominal and visceral fat was highest in the obese groups. Compared with age- and BMI-matched metabolically healthy counterparts, the unhealthy (lean or obese) individuals had higher liver fat and decreased early diastolic strain rate, early diastolic tissue velocity and systolic strain indicative of subclinical systolic and diastolic dysfunction. The magnitude of dysfunction correlated with the number of components of metabolic syndrome but not with BMI or with the degree of ectopic (visceral or liver) fat deposition. CONCLUSIONS: Myocardial dysfunction appears to be related to poor metabolic health rather than simply BMI or fat mass. These data may partly explain the epidemiological evidence on CVD risk relating to the different obesity phenotypes. PMID- 26271189 TI - Compression-Coated Tablet for Colon Targeting: Impact of Coating and Core Materials on Drug Release. AB - This work was envisaged to develop compression-coated tablets using a blend of Ca(+2) ion cross-linked carboxymethyl xanthan gum (CMXG) and sodium alginate (SAL) for delayed release of immediate pulse release tablets of prednisolone (PDL) in the colon without the need of colonic bacterial intervention for degradation of the polysaccharide coat. The core tablets containing PDL and other compatible excipients were prepared by direct compression method and subsequently compression coated with different ratios of CMXG and SAL. Long T lag, the time required to restrict the drug release below 10%, and short T rap, the time required for immediate release following the T lag, were considered as suitable release parameters for evaluation of colon targeting of PDL tablets. Among the various compression coats, a blend of CMXG and SAL in a ratio of 1.5:3.5 provided T lag of 5.12 +/- 0.09 h and T rap of 6.50 +/- 0.05 h. The increase in microcrystalline cellulose (MCC) and crospovidone (CP) in the core tablets did not change T lag significantly although decreased the T rap marginally. Inclusion of an osmogen in the core tablets decreased the T lag to 4.05 +/- 0.08 h and T rap to 3.56 +/- 0.06 h. The increase in coat weight to 225 mg provided a reasonably long T lag (6.06 +/- 0.09 h) and short T rap (4.36 +/- 0.20 h). Drug release from most of the formulations followed the Hixson-Crowell equation and sigmoidal pattern as confirmed by the Weibull equation. In conclusion, tablets, compression coated with CMXG and SAL in a ratio of 1.5:3.5 and having 225-mg coat weight, were apparently found suitable for colon targeting. PMID- 26271190 TI - Apoptosis Susceptibility Prolongs the Lack of Memory B Cells in Acute Leukemic Patients After Allogeneic Hematopoietic Stem Cell Transplantation. AB - Long-term survival after allogeneic hematopoietic stem cell transplantation requires intact immunosurveillance, which is hampered by lymphoid organ damage associated with conditioning therapy, graft-versus-host disease, and immunosuppression. Our study aimed to identify the mechanisms contributing to sustained low memory B cell numbers after transplantation. Peripheral B and T cell subset recovery and functional marker expression were investigated in 35 acute leukemic patients up to 1 year after transplantation. Apoptosis of B cells after CD40/TLR-9, CD40/BCR, and CD40/BCR/TLR-9-dependent stimulation and drug efflux capacity were analyzed. One half of the patients suffered from infections after day 180. All patients had strongly diminished CD27(+) memory B cells despite already normalized total B cell numbers and fully recovered CD27(-)IgD(-) memory B cells, putatively of extra-follicular origin. Circulating memory follicular helper T cells were reduced in the majority of patients as well. Naive B cells exhibited a decreased expression of CXCR5, which mediates follicular B cell entry. Additionally, a lower HLA-DR expression was found on naive B cells, impairing antigen presentation. Upon CD40/TLR-9-dependent activation, B cells underwent significantly increased apoptosis paralleled by an aberrant up regulation of Fas-L on activated T cells and Fas on resting B cells. Significantly increased B cell apoptosis was also observed after CD40/BCR and CD40/BCR/TLR-9-dependent activation. Drug efflux capacity of naive B cells was diminished in cyclosporin A-treated patients, additionally contributing to an apoptosis-prone phenotype. We conclude that B cell survival and migration and T cell communication defects are contributing candidates for an impaired germinal center formation of memory B cells after allogeneic hematopoietic stem cell transplantation. Follow-up studies should evaluate effectiveness of revaccinations on the cellular level and should address the long-term sequelae of B cell defects after transplantation. PMID- 26271192 TI - Comparison of Outcomes for Pediatric Patients With Acute Myeloid Leukemia in Remission and Undergoing Allogeneic Hematopoietic Cell Transplantation With Myeloablative Conditioning Regimens Based on Either Intravenous Busulfan or Total Body Irradiation: A Report From the Japanese Society for Hematopoietic Cell Transplantation. AB - Pediatric patients with acute myeloid leukemia (AML) mainly receive myeloablative conditioning regimens based on busulfan (BU) or total body irradiation (TBI) before allogeneic hematopoietic cell transplantation (allo-HCT); however, the optimal conditioning regimen remains unclear. To identify which of these regimens is better for pediatric patients, we performed a retrospective analysis of nationwide registration data collected in Japan between 2006 and 2011 to assess the outcomes of patients receiving these regimens before a first allo-HCT. Myeloablative conditioning regimens based on i.v. BU (i.v. BU-MAC) (n = 69) or TBI (TBI-MAC) (n = 151) were compared in pediatric AML patients in first or second complete remission (CR1/CR2). The incidences of sinusoid obstruction syndrome, acute and chronic graft-versus-host disease, and early nonrelapse mortality (NRM) before day 100 were similar for both conditioning groups; however, the incidence of bacterial infection during the acute period was higher in the TBI-MAC group (P = .008). Both groups showed a similar incidence of NRM, and there was no significant difference in the incidence of relapse between the groups. Univariate and multivariate analyses revealed no significant differences in the 2-year relapse-free survival rates for the i.v. BU-MAC and TBI-MAC groups in the CR1/CR2 setting (71% versus 67%, P = .36; hazard ratio, .73; 95% CI, .43 to 1.24, respectively). TBI-MAC was no better than i.v. BU-MAC for pediatric AML patients in remission. Although this retrospective registry-based analysis has several limitations, i.v. BU-MAC warrants further evaluation in a prospective trial. PMID- 26271193 TI - Hematopoietic Cell Transplantation after Solid Organ Transplantation. AB - Solid organ transplantation (SOT) followed by hematopoietic cell transplantation (HCT) has been used to treat a single disease with multiorgan involvement or 2 separate diseases, the first requiring SOT and the second often a possible complication of SOT. Results of such serial transplants have been reported sporadically in the literature, usually as single case studies. Thirteen autologous and 27 allogeneic HCTs after SOT published previously are summarized. A more detailed review is provided for an additional 16 patients transplanted at a single institution, 8 of whom had autologous and 8 of whom had allogeneic HCT after SOT. Five of 8 autologous transplant recipients are alive a median of 4.6 years after HCT. Four of 8 allogeneic HCT recipients are alive a median of 8.7 years after HCT. In carefully selected patients, HCT after SOT is feasible and associated with a low incidence of either solid organ or hematopoietic cell rejection. PMID- 26271191 TI - Robust Vaccine Responses in Adult and Pediatric Cord Blood Transplantation Recipients Treated for Hematologic Malignancies. AB - Because cord blood (CB) lacks memory T and B cells and recent decreases in herd immunity to vaccine-preventable diseases in many developed countries have been documented, vaccine responses in CB transplantation (CBT) survivors are of great interest. We analyzed vaccine responses in double-unit CBT recipients transplanted for hematologic malignancies. In 103 vaccine-eligible patients, graft-versus-host disease (GVHD) most commonly precluded vaccination. Sixty-five patients (63%; engrafting units median HLA-allele match 5/8; range, 2 to 7/8) received protein conjugated vaccines, and 63 patients (median age, 34 years; range, .9 to 64) were evaluated for responses. Median vaccination time was 17 months (range, 7 to 45) post-CBT. GVHD (n = 42) and prior rituximab (n = 13) delayed vaccination. Responses to Prevnar 7 and/or 13 vaccines (serotypes 14, 19F, 23F) were seen in children and adults (60% versus 49%, P = .555). Responses to tetanus, diphtheria, pertussis, Haemophilus influenzae, and polio were observed in children (86% to 100%) and adults (53% to 89%) even if patients had prior GVHD or rituximab. CD4(+)CD45RA(+) and CD19(+) cell recovery significantly influenced tetanus and polio responses. In a smaller cohort responses were seen to measles (65%), mumps (50%), and rubella (100%) vaccines. No vaccine side effects were identified, and all vaccinated patients survived (median follow-up, 57 months). Although GVHD and rituximab can delay vaccination, CBT recipients (including adults and those with prior GVHD) have similar vaccine response rates to adult donor allograft recipients supporting vaccination in CBT recipients. PMID- 26271195 TI - A small-scale open-label study of the treatment of canine flea allergy dermatitis with fluralaner. AB - BACKGROUND: Fluralaner is an isoxazoline systemic insecticide and acaricide that provides persistent flea-killing activity on dogs for 12 weeks. European and US field studies have shown that fluralaner treatment alleviates the signs of flea allergy dermatitis (FAD) in client-owned dogs. HYPOTHESIS/OBJECTIVE: To assess the clinical response in FAD affected dogs over the 12-week period following a single oral fluralaner treatment. ANIMALS: Twenty client-owned dogs were diagnosed with FAD on the basis of compatible clinical signs and a positive response in flea antigen tests, using intradermal and or serological methods. METHODS: An open-label small-scale study with all dogs receiving a single oral fluralaner treatment. All enrolled dogs were diagnosed with FAD and then clinically monitored at 4-week intervals for 12 weeks. Twenty dogs completed the study. RESULTS: All dogs were flea-free at all post-treatment assessments except for one dog that had a single flea at the first post-enrollment assessment at 4 weeks. At the 4-week post-treatment assessment active FAD signs had resolved in all dogs; at 8 weeks post-treatment, two dogs showed mild signs. All clinical signs of FAD had resolved at the final assessment of 12 weeks after treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: A single administration of fluralaner alleviated or resolved signs associated with FAD in all treated dogs over the recommended 12-week treatment period. PMID- 26271194 TI - Suitability Criteria for Adult Related Donors: A Consensus Statement from the Worldwide Network for Blood and Marrow Transplantation Standing Committee on Donor Issues. AB - The number of allogeneic hematopoietic stem cell (HSC) transplants performed globally each year continues to increase. Advances in HLA typing, better supportive care, and administration of reduced-intensity conditioning regimens allow treatment of older patients with older sibling donors. Pretransplant donor assessment and testing are very important processes affecting the quality and safety of donation. For unrelated HSC donors detailed recommendations for health assessment have been published, allowing donation only if they are unrestrictedly healthy. Eligibility criteria for related donors are less strict and vary significantly between centers. In situations where a family donor does not meet the suitability criteria for unrelated donors, involved physicians often struggle with the decision whether the matched relative is suitable for donation or not. On behalf of the Worldwide Network for Blood and Marrow Transplantation Standing Committee on Donor Issues, we intended to develop a consensus document with recommendations for donor workup and final clearance of family donors who would not be able to serve as unrelated donors because of their age or pre-existing diseases. This article covers different topics intending to support decision making, with the goal of minimizing medical risk to the donor and protection of the recipient from transmissible diseases. PMID- 26271196 TI - Impact of early thiopurines on surgery in 2770 children and young people diagnosed with inflammatory bowel disease: a national population-based study. AB - BACKGROUND: The role of early thiopurine treatment in inflammatory bowel disease (IBD) is unproven. AIM: To quantify the impact of timing and duration of thiopurines on the risk of first surgery in children and young people with IBD using a population-based cohort. METHODS: We constructed an incident cohort of children and young people aged <25 years, diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) from 1990 to 2009. We used Cox proportional hazards modelling to determine the impact of early thiopurine use, commenced within a year of diagnosis on risk of first surgery. RESULTS: We identified 1595 and 1175 incident cases of CD and UC respectively with a mean length of follow-up of 4.3 years/person. There were 216 (13.5%) and 73 (6.2%) surgeries for CD and UC patients between 1990 and 2009 respectively. In CD among thiopurine users, the absolute risk of surgery at 5 years for early thiopurine use vs. late was 15.3% (95% CI: 10.5-22.1) vs. 22.1% (95% CI: 18.1-26.9) respectively. After adjustment, the early use of thiopurines was associated with a reduction in risk of first surgery of 39% (HR 0.61, 95% CI: 0.41-0.91) over the 20-year study period. In UC, early thiopurine use offered no additional benefit. CONCLUSIONS: In Crohn's disease, early treatment with thiopurines in children and young people is associated with an appreciable reduction in the risk of surgery, but early treatment does not reduce surgical risk in UC. PMID- 26271197 TI - The acrosome of eutherian mammals. AB - The acrosome is not just a bag of enzymes, most of which, if not all, are singly non-essential for sperm-oocyte interaction. The Golgi-derived acrosomal cap reveals some extraordinary development and structure particularities. The acrosome of eutherian spermatozoa basically consists of two parts, the anterior and equatorial segments; the present review is devoted to the former, the initial actor in fertilization. Its occasional fanciful morphological changes during epididymal maturation are analyzed, together with its heterogeneous contents: enzymes, zona binding proteins, structural proteins (matrix) and yet to be chemically characterized crystalloids. The plasma and acrosomal membranes present stabilized ordered domains, whereas glycoprotein-free areas appear during capacitation and before fusion. Exocytosis, induced by the cumulus oophorus and/or the zona pellucida, may generally start proximally and progress anteriorly, resulting in the detachment of a hybrid membrane shroud, whose entity is probably maintained by the bound matrix. Immediately released soluble enzymes must be active during the first interactions of the gametes, whereas other lysins, bound to the matrix or stored as proenzymes, are only progressively released. Zona binding is probably achieved via the shroud and/or the IAM (depending on species). Penetration along an incurved slit through the stratified zona is allowed by the rigid and denuded head tip and flagellar hyperactivity, and assisted by the local proteolytic activity of proteasomes bound to the IAM, the unique essential zona lysin system. PMID- 26271199 TI - Exercise echocardiography in asymptomatic severe aortic stenosis. PMID- 26271198 TI - Bayesian analysis of two diagnostic methods for paediatric ringworm infections in a teaching hospital. AB - Quantitatively, conventional methods of diagnosis of tinea capitis or paediatric ringworm, microscopic and culture tests were evaluated with Bayes rule. This analysis would help in quantifying the pervasive errors in each diagnostic method, particularly the microscopic method, as a long-term treatment would be involved to eradicate the infection by the use of a particular antifungal chemotherapy. Secondly, the analysis of clinical data would help in obtaining digitally the fallible standard of the microscopic test method, as the culture test method is taken as gold standard. Test results of 51 paediatric patients were of 4 categories: 21 samples were true positive (both tests positive), and 13 were true negative; the rest samples comprised both 14 false positive (microscopic test positivity with culture test negativity) and 3 false negative (microscopic test negativity with culture test positivity) samples. The prevalence of tinea infection was 47.01% in the population of 51 children. The microscopic test of a sample was efficient by 87.5%, in arriving at a positive result on diagnosis, when its culture test was positive; and, this test was efficient by 76.4%, in arriving at a negative result, when its culture test was negative. But, the post-test probability value of a sample with both microscopic and culture tests would be correct in distinguishing a sample from a sick or a healthy child with a chance of 71.5%. However, since the sensitivity of the analysis is 87.5%, the microscopic test positivity would be easier to detect in the presence of infection. In conclusion, it could be stated that Trychophyton rubrum was the most prevalent species; sensitivity and specificity of treating the infection, by antifungal therapy before ascertaining by the culture method remain as 0.8751 and 0.7642, respectively. A correct/coveted diagnostic method of fungal infection would be could be achieved by modern molecular methods (matrix assisted laser desorption ionisation-time of flight mass spectrometry or fluorescence in situ hybridization or enzyme-linked immunosorbent assay [ELISA] or restriction fragment length polymorphism or DNA/RNA probes of known fungal taxa) in advanced laboratories. PMID- 26271200 TI - Edoxaban for treatment of venous thromboembolism in patients with cancer. Rationale and design of the Hokusai VTE-cancer study. AB - Direct oral anticoagulants may be effective and safe for treatment of venous thromboembolism (VTE) in cancer patients, but they have not been compared with low-molecular-weight heparin (LMWH), the current recommended treatment for these patients. The Hokusai VTE-cancer study is a randomised, open-label, clinical trial to evaluate whether edoxaban, an oral factor Xa inhibitor, is non-inferior to LMWH for treatment of VTE in patients with cancer. We present the rationale and some design features of the study. One such feature is the composite primary outcome of recurrent VTE and major bleeding during a 12-month study period. These two complications occur frequently in cancer patients receiving anticoagulant treatment and have a significant impact. The evaluation beyond six months will fill the current gap in the evidence base for the long-term treatment of these patients. Based on the observation that the risk of recurrent VTE in patients with active cancer is similar to that in those with a history of cancer, the Hokusai VTE-cancer study will enrol patients if whose cancer was diagnosed within the past two years. In addition, patients with incidental VTE are eligible because their risk of recurrent VTE is similar to that in patients with symptomatic disease. The unique design features of the Hokusai VTE-cancer study should lead to enrolment of a broad spectrum of cancer patients with VTE who could benefit from oral anticoagulant treatment. PMID- 26271201 TI - Validation of a gastric cancer nomogram using a cancer registry. AB - BACKGROUND: A Memorial Sloan Kettering (MSKCC) nomogram predicts disease specific survival (DSS) for gastric adenocarcinoma. The goal of this study is to use a cancer registry to compare nomogram predicted survival with actual survival in the general population. METHODS: All patients undergoing surgery for gastric adenocarcinoma from the Surveillance, Epidemiology, and End Results (SEER) database (1988-2012) were studied. RESULTS: 6954 patients were identified. Majority of cancers were in the antrum (30.2%), and had intestinal histology (73.7%). Median follow-up was 8.2 years. Five year DSS for nomogram risk groups (0-25%, 26-50%, 51-75%, and 76-100%) was 23%, 48%, 57%, and 81% respectively. Actual DSS was 7-15% lower than nomogram predicted DSS. Relative to patients in the 76-100% 5-year DSS risk group, patients in the 0-25%, 26-50%, and 51-75% groups had significantly higher risks of death with hazard ratios of 6.84 (95%CI 6.12-7.65), 3.30 (95%CI 2.83-3.86), and 2.64 (95%CI 2.30-3.03), respectively (all P < 0.001). The concordance index for 5-year nomogram predicted DSS was 0.68 (95%CI 0.67-0.69). CONCLUSIONS: The MSKCC gastric cancer nomogram over-estimates DSS from gastric cancer in the general population and has a moderate concordance index. Predictive tools generated at specialized institutions may not perform as well in the general population. PMID- 26271202 TI - TRIzol and Alu qPCR-based quantification of metastatic seeding within the skeleton. AB - Current methods for detecting disseminated tumor cells in the skeleton are limited by expense and technical complexity. We describe a simple and inexpensive method to quantify, with single cell sensitivity, human metastatic cancer in the mouse skeleton, concurrently with host gene expression, using TRIzol-based DNA/RNA extraction and Alu sequence qPCR amplification. This approach enables precise quantification of tumor cells and corresponding host gene expression during metastatic colonization in xenograft models. PMID- 26271203 TI - Quantitative precision of optical frequency domain imaging: direct comparison with frequency domain optical coherence tomography and intravascular ultrasound. AB - No systematic validation study is available with optical frequency domain imaging (OFDI), directly compared with frequency domain optical coherence tomography (FD OCT) and intravascular ultrasound (IVUS). Controversy also remains about the impact of different stent contour tracing methods by OFDI/FD-OCT. In vitro: coronary phantom models (1.51-5.04 mm) were imaged with OFDI, FD-OCT, and IVUS, demonstrating excellent quantitative precision with a slight overestimation of mean lumen diameter (difference 0.01-0.02 mm). In vivo: corresponding 64 OFDI/IVUS images of stented coronary segments from 20 swines were analyzed. Minimum lumen area by OFDI was larger than IVUS at baseline (P < 0.001), whereas it was smaller than IVUS at follow-up. When stent was traced at leading edges of struts by OFDI, minimum stent area was similar between OFDI and IVUS (P = 0.60). When traced at the highest intensity points of struts by OFDI, it was significantly larger in OFDI than in IVUS (P < 0.001). Three modalities have clinically acceptable precision across the wide range of lumen diameters. In vivo measurements by OFDI and IVUS could slightly be discrepant depending on the parameters and time points. In stent assessment by OFDI, the 2 methods led to a small but systematic difference; therefore, consistency in methodology is advised for comparative studies. PMID- 26271205 TI - Hepatitis C virus increases the risk of kidney disease among HIV-positive patients: Systematic review and meta-analysis. AB - Kidney disease has become an important co-morbidity among human immunodeficiency virus-infected patients as they live longer in the era of highly effective antiretroviral therapy. It remains unclear how co-infection with hepatitis C virus impacts on the trajectory of kidney disease among HIV-infected patients. To evaluate the effect of co-infection with HCV on the risk of kidney disease in HIV infected populations. We conducted a systematic review of the published medical literature to determine if hepatitis C co-infection is associated with increased likelihood of chronic kidney disease in HIV-positive adults. We used the random effects model of DerSimonian and Laird to generate a summary estimate of the relative risk for chronic kidney disease (defined by reduced glomerular filtration rate and/or detectable proteinuria) with hepatitis C virus across the published studies. Meta-regression and stratified analysis were also conducted. We identified 19 studies (146,151 unique patients with HIV) and separate meta analyses were performed according to the outcome. Aggregation of longitudinal studies (n = 8, 105,462 unique patients) showed a relationship between HCV infection and increased risk of reduced glomerular filtration rate among HIV infected individuals, the summary estimate for adjusted hazard ratio was 1.64 (95%CI, 1.28; 2.0, P < 0.001) in HIV-HCV co-infected individuals compared with those having HIV mono-infection. No between-studies heterogeneity was noted (P value by Q test = 0.08). HCV positive serology was an independent risk factor for proteinuria; adjusted effect estimate, 1.23 (95% confidence interval, 1.18; 1.28, P = 0.001) (n = 6 studies; 26,835 unique patients). In meta-regression, we noted the impact of ageing (P = 0.0001) upon the adjusted hazard ratio of incidence of reduced glomerular filtration rate among HCV-HIV co-infected patients; a negative association between frequency of males (P = 0.001) and the adjusted hazard ratio of prevalence of low glomerular filtration rate was found. Hepatitis C co infection is associated with a significant increase in the risk of reduced glomerular filtration rate and/or detectable proteinuria among HIV-infected individuals. PMID- 26271207 TI - A highly N-doped carbon phase "dressing" of macroscopic supports for catalytic applications. AB - The straightforward "dressing" of macroscopically shaped supports (i.e.beta-SiC and alpha-Al2O3) with a mesoporous and highly nitrogen-doped carbon-phase starting from food-processing raw materials is described. The as-prepared composites serve as highly efficient and selective metal-free catalysts for promoting industrial key-processes at the heart of renewable energy technology and environmental protection. PMID- 26271206 TI - Greater preference consistency during the Willingness-to-Pay task is related to higher resting state connectivity between the ventromedial prefrontal cortex and the ventral striatum. AB - The significance of why a similar set of brain regions are associated with the default mode network and value-related neural processes remains to be clarified. Here, we examined i) whether brain regions exhibiting willingness-to-pay (WTP) task-related activity are intrinsically connected when the brain is at rest, ii) whether these regions overlap spatially with the default mode network, and iii) whether individual differences in choice behavior during the WTP task are reflected in functional brain connectivity at rest. Blood-oxygen-level dependent (BOLD) signal was measured by functional magnetic resonance imaging while subjects performed the WTP task and at rest with eyes open. Brain regions that tracked the value of bids during the WTP task were used as seed regions in an analysis of functional connectivity in the resting state data. The seed in the ventromedial prefrontal cortex was functionally connected to core regions of the WTP task-related network. Brain regions within the WTP task-related network, namely the ventral precuneus, ventromedial prefrontal and posterior cingulate cortex overlapped spatially with publically available maps of the default mode network. Also, those individuals with higher functional connectivity during rest between the ventromedial prefrontal cortex and the ventral striatum showed greater preference consistency during the WTP task. Thus, WTP task-related regions are an intrinsic network of the brain that corresponds spatially with the default mode network, and individual differences in functional connectivity within the WTP network at rest may reveal a priori biases in choice behavior. PMID- 26271208 TI - Dirac directional emission in anisotropic zero refractive index photonic crystals. AB - A certain class of photonic crystals with conical dispersion is known to behave as isotropic zero-refractive-index medium. However, the discrete building blocks in such photonic crystals are limited to construct multidirectional devices, even for high-symmetric photonic crystals. Here, we show multidirectional emission from low-symmetric photonic crystals with semi-Dirac dispersion at the zone center. We demonstrate that such low-symmetric photonic crystal can be considered as an effective anisotropic zero-refractive-index medium, as long as there is only one propagation mode near Dirac frequency. Four kinds of Dirac multidirectional emitters are achieved with the channel numbers of five, seven, eleven, and thirteen, respectively. Spatial power combination for such kind of Dirac directional emitter is also verified even when multiple sources are randomly placed in the anisotropic zero-refractive-index photonic crystal. PMID- 26271209 TI - The rights and responsibilities of citizenship for service users: some terms and conditions apply. AB - ACCESSIBLE SUMMARY: What is known about the subject? Citizenship is an important yet largely overlooked concept within psychiatric and mental health nursing practice Many service users are subject to legally mandated restrictions that place conditions on their rights and responsibilities as citizens. What this paper adds to existing knowledge? Even though service users have legal status as citizens, they continue to experience many conditions on their rights and responsibilities. Concerns about services users' trustworthiness and doubts about their levels of insight impact on their status as full citizens. What are the implications for practice? Nurses' understandings of the conditions placed on the citizenship rights and responsibilities of service users will ensure inclusive and less restrictive care and treatment Integration of the principles of therapeutic reciprocity and procedural justice within practice will help nurses balance both the rights of services users and legal restrictions on their liberty and autonomy ABSTRACT: INTRODUCTION: Service users have long been lobbying for equal participation as citizens, yet citizenship is an important and largely overlooked concept within nursing education and practice. AIMS: The study explored service users' understandings of their rights and responsibilities of citizenship and the conditions placed on these. METHODS: A total of 17 service users participated in semi-structured interviews. Isin's theory of the content of citizenship was used to analyze the data using a framework approach. RESULTS: Service users experience conditional citizenship that includes barriers to their participation and their rights and responsibilities that others in society enjoy. DISCUSSION: When the world of the service user is constructed through the language of the biomedical model, nurses may unwittingly reinforce psychiatric labels and thus perpetuate the stereotype that service users lack the competence to fully enact their rights and responsibilities. IMPLICATIONS FOR PRACTICE: When providing care, nurses should incorporate the notion of therapeutic jurisprudence and the principles of reciprocity, procedural justice and the implementation of advanced directives to reduce conditions on service users' status as citizens. PMID- 26271212 TI - Post-Ebolavirus disease syndrome: What do we know? AB - As the current Zaire ebolavirus disease outbreak in West Africa fades, the health problems of the more than 16,500 survivors have come to light. A wide range of mental and physical symptoms may occur during the convalescence stage. Reported symptoms of "post-Ebolavirus disease syndrome" (PEVDS) include chronic joint and muscle pain, fatigue, anorexia, hearing loss, blurred vision, headache, sleep disturbances, low mood and short-term memory problems. PEVDS has been associated with a decrease in functionality and difficulties to return to work. Further studies are needed to fully categorize the clinical spectrum of PEVDS. Diagnostic criteria and surrogate markers for the early diagnosis of PEVDS, and implementation of specialized health services to treat and follow-up survivors are also needed. PMID- 26271211 TI - Erratum to: DHEA metabolism to the neurosteroid androsterone: a possible mechanism of DHEA's antidepressant action. PMID- 26271210 TI - Involvement of endoplasmic reticulum stress in optic nerve degeneration after chronic high intraocular pressure in DBA/2J mice. AB - DBA/2J mice are one of several animal strains used for experimental models of both intraocular hypertension and glaucoma. This study investigates the relationship between endoplasmic reticulum (ER) stress and optic nerve degeneration in DBA/2J mice. Intraocular pressure (IOP) was measured in DBA/2J mice between the ages of 6 and 15 months. Optic nerve damage was assessed at 15 months of age. The nerve was immunostained with antibodies to either neurofilament heavy chain (NFH) or phosphorylated NFH (pNFH), and optic nerve damage was assessed by performing NFH- and pNFH-positive axon counts. Expression levels of the ER stress proteins 78-kDa glucose-regulated protein, also known as binding immunoglobulin protein, and C/EBP homologous protein were assayed with Western blotting. We also investigated ER stress localization in the optic nerve by double immunostaining with antibodies to ionized calcium-binding adaptor molecule 1, myelin basic protein, and glial fibrillary acidic protein (GFAP). In DBA/2J mice, IOP began to rise at 8 months of age, and retinal degeneration was detected at 15 months of age. DBA/2J mice had fewer axons than controls at 15 months of age. ER stress-related protein levels were higher in the optic nerves of DBA/2J mice and were colocalized with GFAP-positive astrocytes. Our findings suggest that ER stress plays a role in optic nerve degeneration during chronic ocular hypertension. Furthermore, ER stress may be related in some way to astrocyte activation. PMID- 26271213 TI - Text analysis tools for identification of emerging topics and research gaps in conservation science. AB - Keeping track of conceptual and methodological developments is a critical skill for research scientists, but this task is increasingly difficult due to the high rate of academic publication. As a crisis discipline, conservation science is particularly in need of tools that facilitate rapid yet insightful synthesis. We show how a common text-mining method (latent Dirichlet allocation, or topic modeling) and statistical tests familiar to ecologists (cluster analysis, regression, and network analysis) can be used to investigate trends and identify potential research gaps in the scientific literature. We tested these methods on the literature on ecological surrogates and indicators. Analysis of topic popularity within this corpus showed a strong emphasis on monitoring and management of fragmented ecosystems, while analysis of research gaps suggested a greater role for genetic surrogates and indicators. Our results show that automated text analysis methods need to be used with care, but can provide information that is complementary to that given by systematic reviews and meta analyses, increasing scientists' capacity for research synthesis. PMID- 26271214 TI - Editorial Comment on "Sex Offenders Seeking Treatment for Sexual Dysfunction Ethics, Medicine, and the Law". PMID- 26271204 TI - Impact of gender on efficacy and acute toxicity of alkylating agent -based chemotherapy in Ewing sarcoma: secondary analysis of the Euro-Ewing99-R1 trial. AB - BACKGROUND: Based on the randomised Euro-EWING99-R1 trial, vincristine, adriamycin, cyclophosphamide (VAC) may be able to replace vincristine, adriamycin, ifosfamide (VAI) in the treatment of standard-risk Ewing sarcoma. However some heterogeneity of treatment effect by gender was observed. The current exploratory study aimed at investigating the influence of gender on treatment efficacy and acute toxicity. PATIENTS AND METHODS: Impact of gender on event-free survival (EFS), acute toxicity by course, switches between treatment arms and cumulative dose of alkylating agents was evaluated in multivariable models adjusted for age including terms to test for heterogeneity of treatment effect by gender. The analysis of the EFS was performed on the intention-to-treat population. RESULTS: EFS did not significantly differ between the 509 males and 347 females (p=0.33), but an interaction in terms of efficacy was suspected between treatment and gender (p=0.058): VAC was associated with poorer EFS than VAI in males, hazard ratio (HR) (VAC/VAI)=1.37 [95% confidence interval (CI), 0.98-1.90], contrasting with HR=0.81 [95%CI, 0.53-1.24] in females. Severe toxicity was more frequent in females, whatever the toxicity type. Thirty patients switched from VAI to VAC (9/251 males, 4%, and 21/174 females, 12%) mostly due to renal toxicity, and three from VAC to VAI (2/258 males, 0.8%, and 1/173 females, 0.6%). A reduction of alkylating agent cumulative dose >20% was more frequent in females (15% versus 9%, p=0.005), with no major difference between VAC and VAI (10% versus 13%, p=0.15). CONCLUSION: Differences of acute toxicity rate and cumulative doses of alkylating agents could not explain the marginal interaction observed in the Euro-EWING99-R1 trial data. Effects of gender-dependent polymorphism/activity of metabolic enzymes (e.g. known for CYP2B6) of ifosfamide versus cyclophosphamide should be explored. External data are required to further evaluate whether there is heterogeneity of alkylating agent effect by gender. TRIAL NUMBERS: NCT00987636 and EudraCT 2008-003658-13. PMID- 26271215 TI - Long-term outcomes of laparoscopic repair of cystocoele. AB - BACKGROUND: There is little information on the effectiveness of laparoscopic techniques for native tissue repair of cystocoele. AIM: To assess the long-term outcome of laparoscopic cystocoele repair. METHODS: Two hundred and twenty-three women with symptomatic pelvic organ prolapse underwent laparoscopic paravaginal repair and treatment of associated conditions. Women were assessed pre operatively and postoperatively at 6 weeks, 6 months, 12 months and then annually or biannually with pelvic organ prolapse quantification (POPQ) and subjective assessment at each visit. RESULTS: Median follow-up was 5.2 years (range: 1-12 years) with 140 women (63%) followed for at least 5 years. During follow-up, 79% of women developed prolapse of at least POPQ stage 2 in one or more compartments and 58% became symptomatic again. Overall, 48% underwent further prolapse surgery, but only 24% of women had an anterior prolapse beyond the hymen. Thirty per cent eventually had a further cystocoele repair. CONCLUSION: Long-term follow up of laparoscopic cystocoele repair shows that cystocoeles are difficult to repair successfully. PMID- 26271216 TI - Biomimetic apatite-based composite materials obtained by spark plasma sintering (SPS): physicochemical and mechanical characterizations. AB - Nanocrystalline calcium phosphate apatites are biomimetic compounds analogous to bone mineral and are at the origin of the bioactivity of most biomaterials used as bone substitutes. Their unique surface reactivity originates from the presence of a hydrated layer containing labile ions (mostly divalent ones). So the setup of 3D biocompatible apatite-based bioceramics exhibiting a high reactivity requests the development of "low" temperature consolidation processes such as spark plasma sintering (SPS), in order to preserve the characteristics of the hydrated nanocrystals. However, mechanical performances may still need to be improved for such nanocrystalline apatite bioceramics, especially in view of load bearing applications. The reinforcement by association with biopolymers represents an appealing approach, while preserving the advantageous biological properties of biomimetic apatites. Herein, we report the preparation of composites based on biomimetic apatite associated with various quantities of microcrystalline cellulose (MCC, 1-20 wt%), a natural fibrous polymer. The SPS consolidated composites were analyzed from both physicochemical (X-ray diffraction, Fourier transform infrared, solid state NMR) and mechanical (Brazilian test) viewpoints. The preservation of the physicochemical characteristics of apatite and cellulose in the final material was observed. Mechanical properties of the composite materials were found to be directly related to the polymer/apatite ratios and a maximum crushing strength was reached for 10 wt% of MCC. PMID- 26271218 TI - Abdominal Aortic Aneurysm as a Long Time Cause of Low Back Pain and Vertebral Scalloping. PMID- 26271217 TI - Preparation and characterization of fibrous chitosan-glued phosphate glass fiber scaffolds for bone regeneration. AB - Phosphate glass fibers (PGF) have emerged as promising building blocks for constructing bone scaffolds. In this study, fibrous scaffolds (PGFS) were fabricated using a facile binding method at room temperature. PGFS exhibited an extracellular matrix-like morphology and were composed of PGF as matrix and chitosan as the natural binding glue. They showed an interconnected porous structure with a porosity of ~87% and pore size of 100-500 um. PGFS exhibited the typical compressive stress-strain behaviour of highly porous, low-density, open cell scaffolds. Their yield stress and modulus were ~0.38 and ~2.84 MPa, respectively, with the strength being higher than the lower bound of the compressive strength of cancellous bone. PGFS were degradable and the weight loss was about 25% after immersion in stimulated body fluid (SBF) for 28 days. In addition, the yield stress and the modulus decreased with increasing immersion time in SBF. Apatite formation could be detected on the surface of PGFS within 7 days of immersion in SBF. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide) assay indicated that PGFS were non-cytotoxic against bone marrow stromal cells (bMSCs) after culture for up to 72 h. These results suggest that PGFS could be promising scaffolds for bone regeneration applications. PMID- 26271219 TI - [Biomechanics of implant augmentation]. AB - BACKGROUND: The rising incidence of osteoporotic fractures requires novel treatment strategies. OBJECTIVE: Implant augmentation with bone cement is considered to be a promising approach but the benefits and risks need to be carefully evaluated. METHODS: Experimental investigation of the biomechanical potential and the associated risks with special reference to the osteoporotic proximal femur and proximal humerus. RESULTS: Even small amounts of bone cement (3 ml) applied to the proximal femur in combination with intramedullary nailing led to more than a 50% increase in the number of test cycles before failure. The heat and pressure generated in the bone did not exceed critical thresholds. Short to midterm effects of subchondral cement placement on the adjacent cartilage can be excluded. The risk for cement leakage needs to be considered. CONCLUSION: Implant augmentation offers high biomechanical potential to prevent mechanical complications after fracture fixation in osteoporotic bone. Early and confident mobilization of elderly patients therefore appears to be possible. With appropriate handling, associated risks seem controllable; however, implant augmentation cannot be applied as a routine concept for osteoporotic fracture management. The application requires careful evaluation on a case by case basis under comprehensive consideration of mechanical and biological factors. PMID- 26271220 TI - [Type 2 dens fracture in the elderly and therapy-linked mortality : Conservative or operative treatment]. AB - BACKGROUND: Type II fractures of the odontoid process of the axis are the most common injury of the cervical spine in elderly patients. Only little evidence exists on whether elderly patients should be treated conservatively or surgically. MATERIAL AND METHODS: The mortality and survival probability of 51 patients were determined in a retrospective study. The range of motion, pain and the neck disability index were clinically investigated. RESULTS: Of the 51 patients 37 were treated surgically and 14 conservatively. The conservatively treated group showed a higher mortality (64 % vs. 32 %). Kaplan-Meier analysis revealed a median survival of the conservatively treated group of 29 months, whereby during the first 3 months of treatment this group showed a higher survival probability and afterwards the surgically treated group showed a higher survival probability. The clinical examination of 20 patients revealed limited range of motion of the cervical spine. Additionally, moderate levels of pain and complaints were recorded using the neck disability index. CONCLUSION: Fractures of the odontoid process pose a far-reaching danger for elderly patients. A balanced assessment of the general condition should be carried out at the beginning of treatment of these patients. In the early phase following trauma no differences were found with respect to survival rates but for long-term survival the operatively treated group showed advantages; however, these advantages cannot be causally attributed to the choice of therapy. PMID- 26271221 TI - Hydration status moderates the effects of drinking water on children's cognitive performance. AB - Changes in hydration status throughout the day may affect cognitive performance with implications for learning success in the classroom. Our study tested the hypothesis that the benefit of drinking water on working memory and attention depends upon children's hydration status and renal response to water intake. Fifty-two children aged 9-12 years old were tested under two experimental conditions. The treatment session (Water session) consisted of a standard breakfast with 200 ml water, a baseline test, consumption of 750 ml of water over a period of two hours and subsequently retested. No water was provided after breakfast during the control session. Changes in hydration were assessed via urine samples. Cognitive testing consisted of digit span, pair cancellation, and delayed match to sample tasks. Children who exhibited smaller decreases in urine osmolality following water intake performed significantly better on the water day compared to the control day on a digit-span task and pair-cancellation task. Children who exhibited larger decreases in urine osmolality following water intake performed better on the control day compared to the water day on the digit span task and pair-cancellation task. These results suggest that focusing on adequate hydration over time may be key for cognitive enhancement. PMID- 26271223 TI - Role of astrocytes and microglia in central nervous system inflammation. Introduction. PMID- 26271222 TI - How do mothers manage their preschool children's eating habits and does this change as children grow older? A longitudinal analysis. AB - The practices mothers adopt in relation to feeding their children have been identified as important predictors of children's quality of diet. However, most studies of the impact of these practices on quality of children's diets have been cross-sectional in design, limiting conclusions about change and causality. Previous research has called for qualitative exploration of the way these practices are used in a real-life setting. This study set out to address these gaps in knowledge. At baseline, mothers recruited to a community-based intervention study and who had a preschool child, completed a questionnaire about their use of covert and overt control practices, child food neophobia and demographics. The quality of children's diets was assessed using a validated food frequency questionnaire. Both questionnaires were repeated with the mothers two years later. Complete data at both time points were available for 228 mother child pairs. Four focus group discussions were conducted with 29 mothers of preschool children to explore their experiences of feeding young children. Mothers who increased their use of overt control had children whose level of food neophobia also increased (P = 0.02). Mothers who used more covert control had children with better quality diets at both time points (P = <0.01) and mothers who increased their use of covert control over the two year follow-up had children whose diet quality improved (P = 0.003). These associations were independent of confounders such as mother's level of education. In the focus groups, mothers suggested that feeding young children was stressful and that control was often relinquished in order to reduce conflict at mealtimes. Supporting parents to adopt more covert techniques to control their children's eating habits may be an effective way of improving the quality of young children's diets. PMID- 26271224 TI - Pediatric alveolar soft part sarcoma of the orbit: a case report. AB - Alveolar soft part sarcoma (ASPS) of the orbit is exceedingly rare and little is known regarding its radiologic features. Here, we reviewed the CT and MRI findings of one case of ASPS of the orbit with emphasis on its salient imaging features. PMID- 26271226 TI - Association of sarcopenic obesity with the risk of all-cause mortality: A meta analysis of prospective cohort studies. AB - Many prospective studies have investigated the relationship between sarcopenic obesity (SO) and risk of mortality. However, the results have been controversial. The aim of the present study was to evaluate the association between SO and all cause mortality in adults by a meta-analysis of prospective cohort studies. A systematic literature search was carried out through electronic databases up to September 2014. A total of nine articles with 12 prospective cohort studies, including 35 287 participants and 14 306 deaths, were included in the meta analysis. Overall, compared with healthy subjects, subjects with SO had a significant increased risk of all-cause mortality (pooled HR 1.24, 95% CI 1.12 1.37, P < 0.001), with significant heterogeneity among studies (I(2) = 53.18%, P = 0.0188), but no indication for publication bias (P = 0.7373). Heterogeneity became low and no longer significant in the subgroup analyses by three SO definitions. More importantly, SO, defined by mid-arm muscle circumference and muscle strength criteria, significantly increased the risk of mortality (HR 1.46, 95% CI 1.23-1.73 and 1.23, 1.09-1.38, respectively). The risk of all-cause mortality did not appreciably change considering the geography (USA cohorts and non-USA cohorts) or the duration of follow up (>=10 years and <10 years). However, the risk estimate was only significant in men (HR 1.23, 95% CI 1.08 1.41, P = 0.0017), not in women (HR 1.16, P = 0.1332). The results of the present study show that subjects with SO are associated with a 24% increase risk of all cause mortality, compared with those without SO, in particular in men; the significant association was found independent of geographical location and duration of follow up. PMID- 26271225 TI - Aminoacyl-tRNA synthetase dependent angiogenesis revealed by a bioengineered macrolide inhibitor. AB - Aminoacyl-tRNA synthetases (AARSs) catalyze an early step in protein synthesis, but also regulate diverse physiological processes in animal cells. These include angiogenesis, and human threonyl-tRNA synthetase (TARS) represents a potent pro angiogenic AARS. Angiogenesis stimulation can be blocked by the macrolide antibiotic borrelidin (BN), which exhibits a broad spectrum toxicity that has discouraged deeper investigation. Recently, a less toxic variant (BC194) was identified that potently inhibits angiogenesis. Employing biochemical, cell biological, and biophysical approaches, we demonstrate that the toxicity of BN and its derivatives is linked to its competition with the threonine substrate at the molecular level, which stimulates amino acid starvation and apoptosis. By separating toxicity from the inhibition of angiogenesis, a direct role for TARS in vascular development in the zebrafish could be demonstrated. Bioengineered natural products are thus useful tools in unmasking the cryptic functions of conventional enzymes in the regulation of complex processes in higher metazoans. PMID- 26271228 TI - Mild and Soft Catalyzed Trifluoromethylthiolation of Boronic Acids: The Crucial Role of Water. AB - The most reactive 2nd generation of trifluoromethanesulfenamides undergoes a copper-catalyzed cross-coupling reaction with boronic acids to afford CF3 S molecules. Contrary to the previous methods in the literature, no base addition, no heating, and no large excess of reagents are required to obtain good results. Furthermore, a crucial role of a small amount of water to favor this reaction has been demonstrated. This constitutes the mildest described conditions for such a reaction. PMID- 26271229 TI - Syntactic bootstrapping. AB - Children use syntax to guide verb learning in a process known as syntactic bootstrapping. Recent work explores how syntactic bootstrapping works-how it begins, and how it interacts with progress in syntax acquisition. We review evidence for three claims about the mechanisms and representations underlying syntactic bootstrapping: (1) Learners are biased to represent linguistic knowledge in a usefully abstract mental vocabulary, permitting rapid generalization of newly acquired syntactic knowledge to new verbs. (2) Toddlers collect information about each verb's combinatorial behavior in sentences based on listening experience, before they know anything about the verb's semantic content. (3) Syntactic bootstrapping begins with an unlearned bias to map nouns in sentences one-to-one onto the participant roles in events. These lines of evidence point toward a picture of early verb learning in which shallow structural analyses of sentences are intrinsically meaningful to learners, and in which information about verbs' combinatorial behavior pervades the lexicon from very early in development. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271230 TI - Language and brain. AB - The human faculty of language has been the focus of researchers from different disciplines such as linguistics, psychology, neurology, biology, anthropology, and more recently genetics. However, the mystery of how the human brain acquires and represents language to ensure its fast and effortless use has still not been entirely solved, although our knowledge base has enlarged dramatically over the past decades. Based on functional magnetic resonance imaging (fMRI) studies, we are today able to define separate frontotemporal neural networks for the processing of syntactic and semantic information in the left hemisphere and for prosodic processes in the right. Data from electro- and magnetencephalographic (EEG/MEG) studies allow us to describe the interaction of these processes in time. Patients with lesions in language-relevant brain structures provide crucial information for the validation of neurocognitive models. These models of adult language systems are used as a template against which the neural basis of first language acquisition and second language processing are investigated. The adult language system is characterized by fast processes supported by Broca's area in the prefrontal cortex and Wernicke's area in the temporal cortex. During language learning in adulthood, these processing routines slowly develop initially recruiting brain regions beyond those of the neural language network involved in adult native language processing. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271227 TI - Cancer in women after assisted reproductive technology. AB - OBJECTIVE: To evaluate the risk of cancer after assisted reproductive technology (ART) therapy. DESIGN: Longitudinal cohort study. SETTING: Not applicable. PATIENT(S): New York, Texas, and Illinois residents between 2004 and 2009, treated with ART, comprising cycles of 113,226 women, including 53,859 women without prior ART treatment, who were linked to their respective state cancer registries and whose cycles were reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System (SART CORS). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Diagnosis of cancer, as reported to the state cancer registry; standardized incidence ratios (SIR) and their 95% confidence intervals, comparing the observed to expected cancer cases based on age-specific cancer rates in the general population of each state. RESULT(S): Among the cohort of women without prior ART therapy, hazard ratios (HR) and 95% confidence intervals (CI) were calculated for treatment parameters and reproductive history factors. The mean follow-up period was 4.87 years; among women without prior ART, 450 women developed 460 cancers. Women treated with ART had a statistically significantly lower risk for all cancers (for all women: SIR 0.78; CI, 0.73-0.83; women without prior ART: SIR 0.75; CI, 0.68-0.82), breast cancer, and all female genital cancers; a non-statistically-significant lower risk for endocrine and uterine cancer; and a non-statistically-significant higher risk for melanoma and ovarian cancer. Among women without prior ART, we found no statistically significant increased HR by parity, number of cycles, cumulative follicle-stimulating hormone dosage, or cycle outcome. CONCLUSION(S): Women initiating ART treatment have no greater risk for developing cancer after nearly 5 years of follow-up compared with the general population and with other women treated with ART. PMID- 26271231 TI - Social cognition. AB - Social cognition research investigates the way information present in the social environment is represented and used in adaptively guiding behavior. Representations of persons and of social relationships form the basic building blocks of social cognition, and we review what is known about how such representations are constructed and constituted. In particular, we review a range of mechanisms whereby observers can infer the psychological qualities of the actors they encounter, including relatively automatic processes as well as more thoughtful and deliberative ones. Prominent approaches for situating person representations within the context of interpersonal relationships are also reviewed. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271232 TI - The self: as a construct in psychology and neuropsychological evidence for its multiplicity. AB - What is the self? Philosophers and psychologists pursuing an answer to this question immediately find themselves immersed in a host of questions about mind and body, subject and object, object and process, the homunculus, free will, self awareness, and a variety of other puzzling matters that largely have eluded satisfying theoretical explication. In this paper I argue that some of this difficulty is attributable to our implicit, phenomenologically-based belief that the self is unitary entity-i.e., a singular "I" that remembers, chooses, thinks, plans, and feels. In this article I address the question of what the self is by reviewing research, conducted primarily with neuropsychological participants, that converges on the idea that the self may be more complex and differentiated than many previous treatments of the topic have assumed. Although some aspects of self-knowledge such as episodic recollection may be compromised by cognitive and neurological disorders, other aspects-for instance, semantic trait summaries appear largely intact. Taken together, these findings support the idea that there is no single, unified "I" to be found. Rather, I argue "the" self may best be construed as a set of interrelated, functionally independent systems. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271233 TI - Decision/action, philosophical issues about. AB - Are conscious decisions or intentions ever among the causes of corresponding intentional actions? This article provides conceptual background for an examination of this question, including a discussion of the nature of decisions, intentions, and actions and a sketch of a model of conscious deciding. It also examines evidence that conscious decisions and intentions sometimes play a role in producing corresponding actions. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271234 TI - The split-brain. AB - Research on split-brain individuals started to flourish approximately 70 years ago and has since then significantly contributed to our understanding of hemispheric specialization. This overview aims to capture the essential of its progress. Amongst other things, the disconnection syndrome is exposed through a description of its manifestations on sensory, motor, and cognitive functions. Ground work and recent studies on split-brain individuals are integrated. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271235 TI - Agnosias. AB - The neuropsychological disorder, known as visual agnosia, refers to the impairment in deriving the meaning of a visually presented stimulus, in spite of the affected individual having intact sensory and low-level vision, and normal language and semantic function. This type of disorder is intriguing both clinically and scientifically, and vision scientists have studied visual agnosia as a means of shedding light on how the normal visual system functions. Considerable progress has been made in this domain, in parallel with detailed behavioral and neural investigations of the visual system of neurologically intact individuals and of nonhuman primates. Here, we focus specifically on the neuropsychological studies and provide a broad overview of the wide range of impairments that fall under the label 'visual agnosia', including those acquired following brain damage in premorbidly normal individuals, those that appear to have been present since birth, and those whose onset is late in life and is associated with neurodegeneration. We also outline the different subtypes of visual agnosia, including those that affect primarily the recognition of faces, words, or objects, and we lay out some of the key questions currently being addressed by researchers in this domain. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271236 TI - The archeology of cognitive evolution. AB - This discussion of archeology of cognition is concerned primarily with the evolutionary emergence of the cognition particular to modern humans but there is an implication for the evolution of cognition among modern humans. Archeological evidence can provide important insights into the evolutionary emergence of human cognition, but theoretical considerations are fundamental in understanding what sorts of cognition there might have been between the ape-like common ancestor and modern humans. Archeology is the only source of evidence for the behavior associated with such theoretical stages. Cognitive archeology, therefore, involves an iterative interaction between theory from outside archeology and more or less direct evidence from the past. This review considers the range of possible evidence from archeology and genetics and summarizes some of the results of analysis of nonhuman primates particularly to assess characteristics of the last common ancestor (LCA) of apes and humans. The history of changes in size and shape of the brain since separation from other apes introduces the need to assess the appropriate cognitive theories to interpret such evidence. The review concentrates on two such approaches: Baddeley's working memory model as interpreted by Coolidge and Wynn, and Barnard's interacting cognitive subsystems as it has been elaborated to define the cognitive conditions for hominins between the LCA and modern people. Most of the rest of the review considers how the evidence from stone tools might be consistent with such theoretical models of cognition. This evidence is consistent with views that modern human behavior only emerged in the last 100,000 years (or so) but it gives an explanation for that in terms of cognition. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271237 TI - Assessment of language acquisition. AB - This review addresses questions of what should be assessed in language acquisition, and how to do it. The design of a language assessment is crucially connected to its purpose, whether for diagnosis, development of an intervention plan, or for research. Precise profiles of language strengths and weaknesses are required for clear definitions of the phenotypes of particular language and neurodevelopmental disorders. The benefits and costs of formal tests versus language sampling assessments are reviewed. Content validity, theoretically and empirically grounded in child language acquisition, is claimed to be centrally important for appropriate assessment. Without this grounding, links between phenomena can be missed, and interpretations of underlying difficulties can be compromised. Sensitivity and specificity of assessment instruments are often assessed using a gold standard of existing tests and diagnostic practices, but problems arise if that standard is biased against particular groups or dialects. The paper addresses the issues raised by the goal of unbiased assessment of children from diverse linguistic and cultural backgrounds, especially speakers of non-mainstream dialects or bilingual children. A variety of new approaches are discussed for language assessment, including dynamic assessment, experimental tools such as intermodal preferential looking, and training studies that assess generalization. Stress is placed on the need for measures of the process of acquisition rather than just levels of achievement. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271238 TI - Introspection. AB - Two main questions about introspection are addressed: whether it exists, and whether it is a reliable source of self-knowledge. Most philosophers have assumed that the answers to both questions are positive, whereas an increasing number of cognitive scientists take the view that introspection is either nonexistent (with self-attributions of mental states being made on the same sort of interpretative basis as attributions of mental states to other people) or unreliable. A number of different models of self-knowledge are discussed, and the evidence bearing on the existence and reliability of introspection is reviewed. New experiments are required to tease apart some of the alternatives. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271239 TI - Cultural psychology. AB - Humans are a cultural species, constantly navigating a complex web of culturally bound practices, norms, and worldviews. This article provides a brief overview of the relatively young field of cultural psychology, which investigates the many ways psychology and culture interweave with one another. Highlighting the cultural nature of the human species, it draws upon research on cultural evolution, enculturation, and developmental processes. This review further summarizes a number of cultural differences in how people perceive the self, and the behavioral consequences that follow from these differences, in the domains of internal and external attribution styles, motivations for self-enhancement, approach/avoidance, primary and secondary control, as well as motivations for distinctiveness and conformity. Additionally, the review discusses research on the intersection of culture and emotion, as well as cultural differences in cognition, perception, and reasoning. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271240 TI - Infant memory. AB - This article provides an overview of developments in long-term memory during the first 2 years of life. Results from three of the most commonly used techniques to assess remembering in preverbal infants-visual paired comparison and visual habituation, conjugate reinforcement, and elicited and deferred imitation-are described. They illustrate infants' ability to encode and retain information as well as the rapid improvements in memory in infancy. A distinction between types or forms of memory is provided in the service of considering how infant memory abilities relate to memory development in early childhood. The review also features discussion of the likely sources of age-related changes in memory in infancy, including the basic processes of memory trace formation and developments in the neural substrate that subserve them. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271241 TI - Inductive reasoning. AB - Inductive reasoning entails using existing knowledge or observations to make predictions about novel cases. We review recent findings in research on category based induction as well as theoretical models of these results, including similarity-based models, connectionist networks, an account based on relevance theory, Bayesian models, and other mathematical models. A number of touchstone empirical phenomena that involve taxonomic similarity are described. We also examine phenomena involving more complex background knowledge about premises and conclusions of inductive arguments and the properties referenced. Earlier models are shown to give a good account of similarity-based phenomena but not knowledge based phenomena. Recent models that aim to account for both similarity-based and knowledge-based phenomena are reviewed and evaluated. Among the most important new directions in induction research are a focus on induction with uncertain premise categories, the modeling of the relationship between inductive and deductive reasoning, and examination of the neural substrates of induction. A common theme in both the well-established and emerging lines of induction research is the need to develop well-articulated and empirically testable formal models of induction. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271244 TI - Effect of inhaled corticosteroids on salival composition: a cross-sectional study in patients with bronchial asthma. AB - BACKGROUND: To date, no evidence exists in the literature as to the effects of inhaled corticosteroids (ICs) on salivary composition in patients with bronchial asthma. OBJECTIVE: The aim of this study was to assess the effect of ICs on salival composition. METHODS: Adult patients attending an outpatient respiratory clinic who were classified into two groups (controls and patients with bronchial asthma receiving ICs), were recruited in this cross-sectional study. For each participant, data of clinical records, baseline history of asthma, and regular IC dose were recorded. A sample of stimulated saliva was collected and processed for investigation of mucin 5B (MUC5B), lipoxygenase (LPO), total antioxidant capacity, and 8-hydroxydeoxyguanosine (8-OHdG) levels. RESULTS: Overall, 103 patients (49 controls and 54 patients receiving regular treatment with ICs) were recruited. No differences in comorbidities or smoking habits were observed. Patients treated with high-doses of ICs showed lower levels of salival MUC5B compared with those treated with medium IC doses or those not treated with ICs (1.60 vs. 2.20 vs. 2.53 ng/mL; p = 0.042). CONCLUSION: In patients with asthma, treatment with high-doses of ICs is associated with reduced levels of salivary MUC5B. This effect can explain some of the effects of ICs on oral health. PMID- 26271242 TI - Azadircta indica as a modulator of membrane stability parameters and surface changes during 1,2 dimethylhydrazine-induced colorectal carcinogenesis. AB - OBJECTIVE: The aim of the present study was to study the modulatory potential of Azadirta indica on colonic surface abnormalities and membrane fluidity changes following 1,2 dimethylhydrazine-induced [DMH] colon carcinogenesis. MATERIALS AND METHODS: Brush border membranes [BBM] were isolated from the colon of rats and the viscosity as well as fluidity parameters were assessed by using the membrane extrinsic fluorophore pyrene. RESULTS: DMH treatment resulted in a significant increase in lipid peroxidation [LPO]. Reduced glutathione levels [GSH] and the activities of glutathione reductase [GR], glutathione transferase [GST], superoxide dismutase [SOD], catalase [CAT] and glutathione peroxidase [GPx] were found to be significantly decreased following DMH treatment. On the other hand, supplementation with AI, DMH-treated rats resulted in a significant decrease in the levels of lipid peroxidation but caused a significant increase in the levels of GSH as well in the activities of GR, GST, SOD, CAT and GPx. The results further demonstrated a marked decrease in membrane microviscosity following DMH treatment. On the other hand, a significant increase was observed in the excimer/monomer ratio and fluidity parameter of DMH-treated rats when compared to normal control rats. However, the alterations in membrane microviscosity and the fluidity parameters were significantly restored following A. indica treatment. Further, histological as well as colon surface alterations were also observed following DMH treatment, which however were greatly prevented upon AI co administration. CONCLUSIONS: The study, therefore, concludes that A. indica proves to be useful in modulating the colonic surface abnormalities and membrane stability following DMH-induced colon carcinogenesis. PMID- 26271243 TI - A learnable parallel processing architecture towards unity of memory and computing. AB - Developing energy-efficient parallel information processing systems beyond von Neumann architecture is a long-standing goal of modern information technologies. The widely used von Neumann computer architecture separates memory and computing units, which leads to energy-hungry data movement when computers work. In order to meet the need of efficient information processing for the data-driven applications such as big data and Internet of Things, an energy-efficient processing architecture beyond von Neumann is critical for the information society. Here we show a non-von Neumann architecture built of resistive switching (RS) devices named "iMemComp", where memory and logic are unified with single type devices. Leveraging nonvolatile nature and structural parallelism of crossbar RS arrays, we have equipped "iMemComp" with capabilities of computing in parallel and learning user-defined logic functions for large-scale information processing tasks. Such architecture eliminates the energy-hungry data movement in von Neumann computers. Compared with contemporary silicon technology, adder circuits based on "iMemComp" can improve the speed by 76.8% and the power dissipation by 60.3%, together with a 700 times aggressive reduction in the circuit area. PMID- 26271245 TI - Tectonic control on the persistence of glacially sculpted topography. AB - One of the most fundamental insights for understanding how landscapes evolve is based on determining the extent to which topography was shaped by glaciers or by rivers. More than 10(4) years after the last major glaciation the topography of mountain ranges worldwide remains dominated by characteristic glacial landforms such as U-shaped valleys, but an understanding of the persistence of such landforms is lacking. Here we use digital topographic data to analyse valley shapes at sites worldwide to demonstrate that the persistence of U-shaped valleys is controlled by the erosional response to tectonic forcing. Our findings indicate that glacial topography in Earth's most rapidly uplifting mountain ranges is rapidly replaced by fluvial topography and hence valley forms do not reflect the cumulative action of multiple glacial periods, implying that the classic physiographic signature of glaciated landscapes is best expressed in, and indeed limited by, the extent of relatively low-uplift terrain. PMID- 26271246 TI - Reliability of pedigree-based and genomic evaluations in selected populations. AB - BACKGROUND: Reliability is an important parameter in breeding. It measures the precision of estimated breeding values (EBV) and, thus, potential response to selection on those EBV. The precision of EBV is commonly measured by relating the prediction error variance (PEV) of EBV to the base population additive genetic variance (base PEV reliability), while the potential for response to selection is commonly measured by the squared correlation between the EBV and breeding values (BV) on selection candidates (reliability of selection). While these two measures are equivalent for unselected populations, they are not equivalent for selected populations. The aim of this study was to quantify the effect of selection on these two measures of reliability and to show how this affects comparison of breeding programs using pedigree-based or genomic evaluations. METHODS: Two scenarios with random and best linear unbiased prediction (BLUP) selection were simulated, where the EBV of selection candidates were estimated using only pedigree, pedigree and phenotype, genome-wide marker genotypes and phenotype, or only genome-wide marker genotypes. The base PEV reliabilities of these EBV were compared to the corresponding reliabilities of selection. Realized genetic selection intensity was evaluated to quantify the potential of selection on the different types of EBV and, thus, to validate differences in reliabilities. Finally, the contribution of different underlying processes to changes in additive genetic variance and reliabilities was quantified. RESULTS: The simulations showed that, for selected populations, the base PEV reliability substantially overestimates the reliability of selection of EBV that are mainly based on old information from the parental generation, as is the case with pedigree-based prediction. Selection on such EBV gave very low realized genetic selection intensities, confirming the overestimation and importance of genotyping both male and female selection candidates. The two measures of reliability matched when the reductions in additive genetic variance due to the Bulmer effect, selection, and inbreeding were taken into account. CONCLUSIONS: For populations under selection, EBV based on genome-wide information are more valuable than suggested by the comparison of the base PEV reliabilities between the different types of EBV. This implies that genome-wide marker information is undervalued for selected populations and that genotyping un-phenotyped female selection candidates should be reconsidered. PMID- 26271248 TI - Are bronchoalveolar lavages a good source for microbial profiling? Differences between throat and bronchoalveolar lavage microbiomes. PMID- 26271247 TI - Alteration in amyloid beta42, phosphorylated tau protein, interleukin 6, and acetylcholine during diabetes-accelerated memory dysfunction in diabetic rats: correlation of amyloid beta42 with changes in glucose metabolism. AB - BACKGROUND: Diabetes accelerates memory dysfunction in a continuous, slowly pathological process. Studies suggest that the time course of certain biomarkers can characterize the pathological course of the disease to provide information for early intervention. Thus, there is an urgent need for validated biomarkers to characterize the cognitive impairment induced by DM. We aimed to detect changes in cerebrospinal fluid biomarkers such as amyloid beta42, phosphorylated tau protein, interleukin 6, and acetylcholine in diabetic rats over time, and to analyse the relationship between diabetes and cognitive impairment. METHODS: Rats were injected once intraperitoneally with 1% of streptozotocin to establish a diabetic model. Index changes were investigated longitudinally and all were measured at the end of the experiment at day 75. Abeta42, P-tau, IL-6, and ACh levels in CSF, insulin levels in plasma, and Abeta42 levels in plasma and brain tissue were measured by ELISA. RESULTS: Compared with control, the diabetic model showed ACh in CSF to be decreased by day 15, continuing lower out to day 75. Abeta42 changes in brain and blood showed the same trends but exhibited minima at different time points: day 30 in CSF and day 15 in plasma. After the minimum, Abeta42 in cerebrospinal fluid rose and levelled off lower than in the control group, whereas Abeta42 in plasma rose and went above the controls at day 30, slowly trending upwards for the remainder of the experiment. P-tau protein in CSF in diabetic rats showed an increasing trend, becoming significantly different from the controls at day 60 and day 75. Abeta42 in CSF was strongly negatively correlated with blood glucose at day 15 and was negatively correlated with insulin in serum, particularly at day 45. CONCLUSION: Our longitudinal research model suggest that changes in the measured biomarkers appear before learning and memory impairments do. Abeta42 and ACh in the diabetes model group clearly changed from day 0 to day 45, and then P-tau and IL-6 varied significantly from day 45 to day 75. The reduced ACh levels observed possibly correlated with the factors common to changes in Abeta42, P-tau, and IL-6. PMID- 26271249 TI - Genetic polymorphisms in XRCC1 genes and colorectal cancer susceptibility. AB - BACKGROUND: The objective of this study is to investigate the association among the polymorphisms of XRCC1 gene, smoking, drinking, family history of tumors, and the risk of colorectal cancer (CRC) in the population of Han nationality in Jiangsu Province, China. METHODS: A case-control study of 320 patients with CRC and 350 cancer-free subjects as a control group was conducted. The three polymorphic sites, codons 194, 280, and 399, of XRCC1 genes were analyzed by PCR RFLP. RESULTS: We find that heavy smoking (>500 cigarettes per year) significantly increased the susceptibility of CRC (OR=1.89, 95% confidence interval (CI) 1.27-2.84) after stratification by total smoking amount. There was also significant difference between cases and controls when family history of tumors (OR=2.96, 95% CI 1.76-4.99) was considered. Comparing with individuals carrying XRCC1 399Arg/Arg genotype, the subjects with 399Arg/Gln (OR=1.46, 95% CI 1.06-2.01) or 399Gln/Gln genotype (OR=1.93, 95% CI 1.05-3.54) had a significantly increased risk for CRC. Taking smoking and drinking habits into consideration, we found that subjects with heavy smoking history and XRCC1 194Arg allele had the significantly increased risk for CRC (OR=2.91, 95% CI 1.35-6.24). Individuals, who carry 399Gln allele and have a heavy smoking (OR=2.72, 95% CI 1.52-4.89) or drinking habit (OR=1.98, 95% CI 1.06-3.67), also have higher risk. In smoking population, 194Arg (P=0.491) and 399Gln (P=0.912) had not significantly increased risk for CRC, so did 399Gln (P=0.812) in smoking population. CONCLUSIONS: Individuals carrying XRCC1 399Gln allele with a smoking or drinking habit were in increased risk, and heavy-smoking subjects with 194Arg allele also have higher risk for CRC in the Han nationality population of Jiangsu Province, which also showed a positive correlation with exposure dose of tobacco. But XRCC1 399Gln allele or 194Arg allele were not independent risk factors for CRC in smoking or drinking population. PMID- 26271250 TI - FORENSIC Autopsy of People Having Committed Suicide in 2002 and in 2012: Comparison of Epidemiological and Sociological Data. AB - This work compares epidemiological and sociological data on persons having committed suicide in 2002 and in 2012 through a retrospective study of every suicide case having led to an autopsy at the Institute for Forensic Medicine of Lyon in 2002 and in 2012. The study included sociodemographic data, medical data, and toxicological data. A total of 486 cases were included (242 cases in 2002 and 244 cases in 2012). People committing suicide were on average older in 2012 than in 2002 with a larger proportion of over 55. There was also an increase in the proportion of psychiatric antecedents (p < 0.001). Whatever the date of death by suicide, the most affected age range is the 45-54. The results highlight the necessity of bolstering the prevention plans, in particular for people over 45. PMID- 26271251 TI - Prevalence of menopausal symptoms among mid-life women: findings from electronic medical records. AB - BACKGROUND: To assess the prevalence of menopausal symptoms among women prescribed hormone therapy (HT) using electronic medical record data from a regional healthcare organization. METHODS: Retrospective data from the Reliant Medical Group from 1/1/2006-12/31/2011 were assessed for 102 randomly-selected patients. Study eligibility criteria included: females aged 45 to 65; prescribed oral or transdermal HT; no history of breast cancer, venous thromboembolism, stroke, gynecological cancer, or hysterectomy; continuously enrolled in the health plan for 1 year before and after the first observed HT prescription. Prevalence of menopause-related symptoms was analyzed descriptively at both the patient and visit levels. RESULTS: Mean age of patients was 54 years. The most common menopausal symptoms were: hot flushes (40%), night sweats (17%), insomnia (16%), vaginal dryness (13%), mood disorders (12%), and weight gain (12%). Among the 102 patients, 163 individual visits listing menopausal symptoms were identified, of which hot flushes (71 visits) were the most common symptom identified. CONCLUSION: Our findings provide recent data on the types of menopausal symptoms experienced by mid-life women prescribed HT. Electronic medical records may be a rich source of data for future studies of menopausal symptoms in this population. PMID- 26271252 TI - Bipolar risk and mental imagery susceptibility in a representative sample of Chinese adults residing in the community. AB - BACKGROUND: We need to better understand the cognitive factors associated with risk for bipolar disorders. Recent research suggests that increased susceptibility to mental imagery may be one such factor. However, since this research was primarily conducted with Western students and at a single time point, it is not known whether the relationship between imagery susceptibility and bipolar symptoms exists across cultures or within the general community, or whether this relationship remains stable over time. AIM: This study evaluated whether Chinese adults identified as being at high (HR) versus low (LR) risk of developing bipolar disorders showed greater mental imagery susceptibility. We aimed to test whether such a relationship was stable over time by measuring imagery characteristics at baseline and at the 7-week follow-up. METHOD: This prospective study recruited a community sample of N = 80 Chinese adults screened for the absence of neurotic and psychotic disorders. The sample was split into HR (n = 18) and LR (n = 62) groups at baseline based on a criterion cut-off score on a measure of hypomania, the Mood Disorder Questionnaire (MDQ). Participants completed measures of imagery susceptibility and its impact: the Spontaneous Use of Imagery Scale (SUIS) and the Impact of Future Events Scale (IFES), at baseline and 7 weeks later. RESULTS: HR group reported greater tendency to use imagery in daily life (SUIS) and greater emotional impact of prospective imagery (IFES) than LR group at baseline. These results remained stable at follow-up. CONCLUSION: This study provides preliminary evidence for increased susceptibility to mental imagery in individuals at high risk of bipolar disorders recruited from a community sample of Chinese adults. This extends previous research in Western student samples suggesting that imagery (both levels of use and its emotional impact) may be a cognitive factor with cross-cultural relevance that is stable over time. PMID- 26271254 TI - RE: Doll and Peto's Quantitative Estimates of Cancer Risks: Holding Generally True for 35 Years. PMID- 26271253 TI - Mice lacking prostaglandin E receptor subtype 4 manifest disrupted lipid metabolism attributable to impaired triglyceride clearance. AB - Upon high-fat feeding, prostaglandin E receptor subtype 4 (EP4)-knockout mice gain less body weight than their EP4(+/+) littermates. We investigated the cause of the lean phenotype. The mice showed a 68.8% reduction in weight gain with diminished fat mass that was not attributable to reduced food intake, fat malabsorption, or increased energy expenditure. Plasma triglycerides in the mice were elevated by 244.9%. The increase in plasma triglycerides was independent of changes in hepatic very low density lipoprotein (VLDL)-triglyceride production or intestinal chylomicron-triglyceride synthesis. However, VLDL-triglyceride clearance was drastically impaired in the EP4-knockout mice. The absence of EP4 in mice compromised the activation of lipoprotein lipase (LPL), the key enzyme responsible for trafficking of plasma triglycerides into peripheral tissues. Deficiency in EP4 reduced hepatic mRNA expression of the transcriptional factor cAMP response element binding protein H (by 36.8%) and LPL activators, including apolipoprotein (Apo)a5 (by 40.2%) and Apoc2 (by 61.3%). In summary, the lean phenotype of EP4-deficient mice resulted from reduction in adipose tissue and accretion of other peripheral organs caused by impaired triglyceride clearance. The findings identify a new metabolic dimension in the physiologic role played by endogenous EP4. PMID- 26271255 TI - Together We Learn: Analyzing the Interprofessional Internal Medicine Residents' and Master of Public Health Students' Quality Improvement Education Experience. AB - Although the value of interprofessional collaborative education has been promoted, it is unclear how teams of clinical and nonclinical learners perceive this experience. The authors studied an interprofessional quality improvement (QI) curriculum implemented in 2013 integrating internal medicine residents (n = 90) and Master of Public Health (MPH) students (n = 33) at an urban safety net academic medical center. Pre and post curriculum surveys assessed attitudes toward QI and interprofessional education and team performance. Resident attitudes toward learning and engaging in QI work improved at the end of the curriculum. Overall, MPH students demonstrated significantly more positive attitudes about interprofessional learning and work than residents. They also agreed more strongly than residents that patients would benefit if residents and public health students worked together. As health care organizations evolve to become more integrated, it is crucial that interprofessional educational opportunities be developed and evaluated to help encourage a culture of collaboration among health care providers. PMID- 26271256 TI - DeDaL: Cytoscape 3 app for producing and morphing data-driven and structure driven network layouts. AB - BACKGROUND: Visualization and analysis of molecular profiling data together with biological networks are able to provide new mechanistic insights into biological functions. Currently, it is possible to visualize high-throughput data on top of pre-defined network layouts, but they are not always adapted to a given data analysis task. A network layout based simultaneously on the network structure and the associated multidimensional data might be advantageous for data visualization and analysis in some cases. RESULTS: We developed a Cytoscape app, which allows constructing biological network layouts based on the data from molecular profiles imported as values of node attributes. DeDaL is a Cytoscape 3 app, which uses linear and non-linear algorithms of dimension reduction to produce data-driven network layouts based on multidimensional data (typically gene expression). DeDaL implements several data pre-processing and layout post-processing steps such as continuous morphing between two arbitrary network layouts and aligning one network layout with respect to another one by rotating and mirroring. The combination of all these functionalities facilitates the creation of insightful network layouts representing both structural network features and correlation patterns in multivariate data. We demonstrate the added value of applying DeDaL in several practical applications, including an example of a large protein protein interaction network. CONCLUSIONS: DeDaL is a convenient tool for applying data dimensionality reduction methods and for designing insightful data displays based on data-driven layouts of biological networks, built within Cytoscape environment. DeDaL is freely available for downloading at http://bioinfo out.curie.fr/projects/dedal/. PMID- 26271257 TI - Sampling strategies for phlebotomine sand flies (Diptera: Psychodidae) in Europe. AB - The distribution of phlebotomine sand flies is widely reported to be changing in Europe. This can be attributed to either the discovery of sand flies in areas where they were previously overlooked (generally following an outbreak of leishmaniasis or other sand fly-related disease) or to true expansion of their range as a result of climatic or environmental changes. Routine surveillance for phlebotomines in Europe is localized, and often one of the challenges for entomologists working in non-leishmaniasis endemic countries is the lack of knowledge on how to conduct, plan and execute sampling for phlebotomines, or how to adapt on-going sampling strategies for other haematophagous diptera. This review brings together published and unpublished expert knowledge on sampling strategies for European phlebotomines of public health concern in order to provide practical advice on: how to conduct surveys; the collection and interpretation of field data; suitable techniques for the preservation of specimens obtained by different sampling methods; molecular techniques used for species identification; and the pathogens associated with sand flies and their detection methods. PMID- 26271258 TI - Violent and non-violent methods of attempted and completed suicide in Swedish young men: the role of early risk factors. AB - BACKGROUND: There is a paucity of studies on the role of early risk factors for the choice of methods for violent suicide attempts. Adolescent risk factors for the choice of violent or non-violent methods for suicide attempts and the risk of subsequent suicide were studied using a longitudinal design. METHODS: A national Swedish cohort of 48 834 18-20-year-old young men conscripted for military service from 1969 to 1970 was followed through official registers during a 37 year period. Two questionnaires concerning their psychosocial background were answered by each conscript. Cox proportional hazard regression analyses were used to estimate the risk for different methods of attempted suicide and later suicide. RESULTS: A total of 1195 (2.4 %) men had made a suicide attempt and of these, 133 (11.1 %) committed suicide later. The number of suicide victims among the non-attempters was 482 (1 %). Half of the suicides occurred during the same year as the attempt. Suicide victims had earlier onset of suicidal behaviour and had more often used hanging as a method of attempted suicide than those who did not later commit suicide. The early risk factors for both violent and non-violent methods of suicide attempt were quite similar. CONCLUSION: Violent suicide attempts, especially by hanging, are associated with a clearly elevated suicide risk in men and require special clinical and public health attention. The early risk factors related to the choice of either a violent or a non-violent suicide attempt method are interlinked and circumstantial factors temporally close to the suicide attempt, such as access to a specific method, may partly explain the choice of method. PMID- 26271259 TI - Risk and protective factors for falls on one level in young children: multicentre case-control study. AB - BACKGROUND: Childhood falls are an important global public health problem, but there is lack of evidence about their prevention. Falls on one level result in considerable morbidity and they are costly to health services. OBJECTIVE: To estimate ORs for falls on one level in children aged 0-4 years for a range of safety behaviours, safety equipment use and home hazards. DESIGN, SETTING AND PARTICIPANTS: Multicentre case-control study at hospitals, minor injury units and general practices in and around four UK study centres. Participants included 582 children less than 5 years of age with a medically attended fall injury occurring at home and 2460 controls matched on age, sex, calendar time and study centre. MAIN OUTCOME MEASURE: Fall on one level. RESULTS: Cases' most common injuries were bangs on the head (52%), cuts or grazes not needing stitches (29%) or cuts or grazes needing stitches (17%). Comparing cases to community controls in the adjusted analyses, significant findings were observed for only two exposures. Injured children were significantly less likely to live in a household without furniture corner covers (adjusted OR (AOR) 0.72, 95% CI 0.55 to 0.95), or without rugs and carpets firmly fixed to the floor (AOR 0.76, 95% CI 0.59 to 0.98). CONCLUSIONS: We did not find any safety practices, use of safety equipment or home hazards associated with a reduced risk of fall on one level. Our findings do not provide evidence to support changes to current injury prevention practice. PMID- 26271260 TI - Precision prevention: time to move beyond universal interventions. PMID- 26271261 TI - The effect of combined mechanism ankle support on postural control of patients with chronic ankle instability. AB - BACKGROUND: Chronic ankle instability is associated with neuromechanical changes and poor postural stability. Despite variety of mechanisms of foot and ankle orthoses, almost none apply comprehensive mechanisms to improve postural control in all subgroups of chronic ankle instability patients. OBJECTIVES: The purpose of this study was to investigate the effect of an ankle support implementing combined mechanisms to improve postural control in chronic ankle instability patients. STUDY DESIGN: Cross-sectional study. METHODS: An ankle support with combined mechanism was designed based on most effective action mechanisms of foot and ankle orthoses. The effect of this orthosis on postural control was evaluated in 20 participants with chronic ankle instability and 20 matched healthy participants. The single-limb stance balance test was measured in both groups with and without the new orthosis using a force platform. RESULTS: The results showed that application of combined mechanism ankle support significantly improved all postural sway parameters in chronic ankle instability patients. There were no differences in means of investigated parameters with and without the orthosis in the healthy group. No statistically significant differences were found in postural sway between chronic ankle instability patients and healthy participants after applying the combined mechanism ankle support. CONCLUSION: The combined mechanism ankle support is effective in improving static postural control of chronic ankle instability patients to close to the postural sway of healthy individual. the orthosis had no adverse effects on balance performance of healthy individuals. Clinical relevance Application of the combined mechanism ankle support for patients with chronic ankle instability is effective in improving static balance. This may be helpful in reduction of recurrence of ankle sprain although further research about dynamic conditions is needed. PMID- 26271262 TI - Influence of heel design in an orthopedic shoe on ground reaction forces during walking. AB - BACKGROUND: One of the treatments prescribed for musculoskeletal patients is orthopedic shoe. The use of an orthopedic shoe is thought to produce a more typical ground reactive force pattern. OBJECTIVES: This study was designed to determine the influence of three heel designs of an orthopedic shoe on the ground reaction forces during walking in healthy subjects. STUDY DESIGN: Quasi experimental. METHOD: In total, 30 healthy adults (12 males, 18 females) walked at a self-selected pace for six trials in each of the three shoe conditions having three different heels which included the following: standard heel, beveled heel, and positive posterior heel flare. For each trial, ground reaction force parameters were recorded using a force plate. RESULTS: Repeated measures analysis of variance indicated that the impact force was significantly reduced for the positive posterior heel flare condition by 8% and 13% compared with standard and beveled heels, respectively (p < 0.001). The first peak of vertical force showed a significant reduction in the beveled heel by 5% and 4% compared with the standard heel and the positive posterior heel flare, respectively (p < 0.001). Loading rate was significantly reduced in the beveled heel and the positive posterior heel flare conditions (p < 0.05). CONCLUSION: Positive posterior heel flare reduced impact force due to its geometry flexibility, while a beveled heel reduced first peak of vertical force. The findings of this study show that the shape of the heel therefore has the potential to modify impact loads during walking. CLINICAL RELEVANCE: This study provides new evidence that by changing shape in the heel of orthopedic shoe impact loads are reduced during walking. Thus, these findings indicate that use of heel design may be beneficial for various musculoskeletal disorders, including key public health problems. PMID- 26271264 TI - The zebra sign: an unknown known. AB - A 65-year-old woman became obtunded following routine laminectomy and was found to have bilateral cerebellar haemorrhage and convexity subarachnoid haemorrhage. We discuss the possible mechanisms of remote cerebellar haemorrhage-cerebellar haemorrhage that develops after spinal or intracranial surgery-giving rise to the 'zebra sign' and the possible mechanism of convexity subarachnoid haemorrhage in this context [corrected]. PMID- 26271263 TI - Hyponatremia during hospitalization and in-hospital mortality in patients hospitalized from heart failure. AB - BACKGROUND: To date, the majority of studies on hyponatremia focussed on hyponatremia at admission, and came from developed countries. This study aimed to identify the prevalence of hyponatremia during hospitalization in patients hospitalized for HF and its association with in-hospital mortality. METHODS: This was an observational study using retrospective data from patients' records between 2010-2013. It focused on those patients carrying an ICD-10 code of 150.0(Congestive Heart Failure) as their primary diagnosis. Hyponatremia during hospitalization was defined as serum sodium level lower than 135 mEq/L obtained from a blood chemistry measurement on the next days after admission. Patients' characteristics were examined and the association between hyponatremia during hospitalization and in-hospital mortality was analyzed. RESULTS: Among 464 patients hospitalized for HF, hyponatremia during hospitalization was observed in 22 % of patients with 44 % of this group had normal serum sodium level on admission. Hyponatremia during hospitalization was associated with lower blood pressure on admission, both systolic and diastolic, peripheral oedema, ascites and fatigue. Patients having history of hospitalization for cardiac diseases and renal failure were higher in patients developing hyponatremia during hospitalization. In this group, amiodarone, heparin, insulin and antibiotics were administered more frequently. Factors potentially increase the risk of hyponatremia during hospitalization include history of fatigue (OR = 3.23, 95 % CI 1.79-5.82), presence of ascites (4.14, 1.84-9.31), and administration of heparin (3.85, 1.78-8.31) and antibiotics (3.08, 1.71-5.53). Length of hospital stay was significantly longer in patients with hyponatremia during hospitalization and in-hospital mortality was also higher compared to non hyponatremic patients, 7.7 % and 29.1 %, respectively. CONCLUSION: This study found that the prevalence of hyponatremia during hospitalization in patients hospitalized for HF was almost the same as hyponatremia on admission and administration of heparin and antibiotics can potentially worsen hyponatremia during hospitalization. In this study population, hyponatremia during hospitalization was found to be associated with in-hospital mortality. PMID- 26271266 TI - Video telemetry: current concepts and recent advances. AB - Epilepsy is a clinical diagnosis based on the history of the patient and of witnesses. Sometimes this is not available or is incomplete, thus making diagnosis uncertain. In other cases, specifically in patients with intractable epilepsy being considered for epilepsy surgery, the diagnosis of epilepsy is not in doubt but the precise localisation of the epileptogenic zone needs to be determined. In both these situations, video telemetry plays a key role and is now a routine in most neuroscience units. This review covers existing practice and the exciting recent development of home video telemetry. PMID- 26271265 TI - Functional cognitive disorder: what is it and what to do about it? AB - To err is human, and it is normal to make minor cognitive errors from time to time. Some people experience persistent subjective cognitive difficulties that cause distress and functional impairment, with no underlying structural, neurodegenerative, toxic or metabolic cause. This is considered a form of functional disorder. In this article, we review functional cognitive disorder and outline its core clinical features. Patients with this are typically of working age and have a source of psychological distress, such as chronic pain, work stress or family difficulties. Its distinction from incipient dementia is difficult and usually requires interval follow-up. Pointers towards possible dementia include abnormal neuroimaging or loss of insight. Many patients accept a functional cognitive disorder diagnosis and willingly engage with psychological therapies but there is no defined optimal treatment. Functional cognitive disorder is common but under-studied; future research priorities include the development of clear diagnostic criteria and robust trials of therapeutic strategies. PMID- 26271267 TI - Evaluation of a low-cost design keratoprosthesis in end-stage corneal disease: a preliminary study. AB - PURPOSE: To evaluate the indications, outcomes and complications of Auro keratoprosthesis (a low-cost design based on type I Boston Keratoprosthesis) in the end-stage corneal disease in a preliminary study. METHODS: In this prospective interventional study, 10 eyes of 10 patients with an end-stage corneal disease underwent implantation of Auro keratoprosthesis with the mean follow-up of 14.5+/-2.1 months. The indications included multiple failed grafts (n=7), aphakic bullous keratopathy (n=2) and chemical injury (n=1). The additional intraoperative procedures performed were synechiolysis (n=9), cataractous lens extraction (n=2), Ahmed glaucoma valve implantation (n=1) and vitreoretinal surgery (n=1). Antibiotic prophylaxis was administered postoperatively, and patients were followed up at 1 week, 2 weeks, 1 month and thereafter at monthly intervals. The main outcome measures were best corrected visual acuity (BCVA), retention of prosthesis, complications and need for secondary surgical interventions. RESULTS: The most common indication for keratoprosthesis implantation was graft failure (7/10, 70%). The postoperative BCVA improved to >=20/200 in six patients. Nine out of 10 patients had retained keratoprosthesis. The complications seen were inflammatory debris behind keratoprosthesis (n=4), retroprosthetic membrane (n=2), glaucoma (n=4), small (<2 mm) sterile stromal necrosis or erosions at the graft edge (n=3) and microbial keratitis (n=1). Explantation of the keratoprosthesis was performed in one eye due to fungal keratitis. CONCLUSIONS: Auro keratoprosthesis, a low-cost keratoprosthesis, is a viable option in the end-stage corneal disease in this preliminary study. Multicentre studies with long-term follow-up are required to conclusively prove its safety and efficacy. PMID- 26271269 TI - New vessels detected on wide-field imaging compared to two-field and seven-field imaging: implications for diabetic retinopathy screening image analysis. AB - INTRODUCTION: Wide-field retinal imaging (Optomap), used for detecting diabetic retinopathy (DR), has been shown to compare well with seven-field early treatment diabetic retinopathy study (ETDRS) photographs. An Optomap 200 degrees image covers 80% of the retinal surface, compared with the standard seven-field, 30 degrees images, covering 30% of the retinal surface. In England, DR screening is performed by grading two, 45 degrees images per eye, by the DR screening service (DRSS). PURPOSE: To assess how often retinal new vessels (NVs) are observed on Optomap imaging, outside the DRSS two fields and standard seven-field photography, in a cohort of patients referred by the DRSS. METHOD: A consecutive series of treatment naive patients with DR, referred from DRSS with pre proliferative or proliferative DR or diabetic maculopathy, were imaged with Optomap colour images, within 3 months of DRSS referral. The incidence and distribution of NVs were recorded in relation to two-field and seven-field areas. RESULTS: NVs were found in 102 of 1562 treatment naive eyes (6.5%) of 781 patients. Of these, 72 were referred from DRSS as having NVs, but an additional 30 eyes (29% of NVs detected) from 25 patients were referred with a lesser degree of DR. In 25 of the 30 eyes without NVs reported on referral, NVs were located outside the standard two fields taken at DRSS, and in 12, NVs were outside the area covered on seven-field imaging (11.7% of eyes with NVs). CONCLUSIONS: Wide field imaging with Optomap detected approximately 30% more NVs than standard two field imaging in patients referred from a UK DRSS. PMID- 26271268 TI - Systematic screening for diabetic retinopathy (DR) in Hong Kong: prevalence of DR and visual impairment among diabetic population. AB - PURPOSE: To determine the prevalence of diabetic retinopathy (DR), sight threatening DR (STDR), visual impairment and other eye diseases in a systematic DR screening programme among primary care Chinese patients with diabetes mellitus (DM) in Hong Kong. METHODS: Screening for DR was provided to all subjects with DM in public primary care using digital fundus photography according to the English national screening programme. STDR was defined as preproliferative DR (R2), proliferative DR (R3) and/or maculopathy (M1). The presence of other eye diseases was noted. Visual impairment was classified as none (visual acuity in the better eye of 6/18 or better), mild (6/18 to >6/60) and severe (6/60 or worse). RESULTS: Of 174 532 subjects screened, most had never been screened before. The prevalence of DR was 39.0% (95% CI 38.8% to 39.2%) and STDR 9.8% (95% CI 9.7% to 9.9%). The most common DR status was R1 (35.7%), followed by M1 (8.6%), R2 (3.0%) and R3 (0.3%). The prevalence of mild and severe visual impairment was 4.2% and 1.3%, respectively. Subjects with STDR had a higher prevalence (9.8%) of visual impairment than those without (3.5%). CONCLUSIONS: DR was prevalent in this population and one in 10 had STDR. This suggests the need for systematic screening to ensure timely referral to an ophthalmologist for monitoring and/or treatment. PMID- 26271270 TI - Uncertain thrombophilia markers. AB - The development of venous thromboembolism (VTE), which includes deep-vein thrombosis and pulmonary embolism, may be associated with inherited or acquired risk factors that can be measured in plasma or DNA testing. The main inherited thrombophilias include the plasma deficiencies of the natural anticoagulants antithrombin, protein C and S; the gain-of-function mutations factor V Leiden and prothrombin G20210A; some dysfibrinogenaemias and high plasma levels of coagulation factor VIII. Besides these established biomarkers, which usually represent the first-level laboratory tests for thrombophilia screening, a number of additional abnormalities have been less consistently associated with an increased VTE risk. These uncertain causes of thrombophilias will be discussed in this narrative review, focusing on their clinical impact and the underlying pathogenetic mechanisms. Currently, there is insufficient ground to recommend their inclusion within the framework of conventional thrombophilia testing. PMID- 26271272 TI - Endogenous event-related potentials in patients with primary Sjogren's syndrome without central nervous system involvement. AB - OBJECTIVES: Endogenous cognitive event-related potentials (CERPs) reflect higher level processing of sensory information and can be used to evaluate cognitive functions. The aim of this paper was to determine whether there are any abnormalities in the electrophysiological parameters of CERPs in patients with primary Sjogren's syndrome (pSS) but without symptoms of central nervous system (CNS) involvement or mental disorder. The analysis of CERP parameters was then correlated with the clinical status of the patients and with some of the immunological parameters in the patient group. METHOD: Thirty consecutive patients with pSS (29 females, one male) were included in the study. All the patients underwent CERP examination. RESULTS: There was a significant prolongation of the latency of P300 and N200 potentials in patients with pSS. Abnormalities in electrophysiological parameters of CERPs correlated with the duration of the disease, salivary gland abnormalities, and elevated erythrocyte sedimentation rate (ESR) values. Patients with coexisting chronic fatigue syndrome (CFS) had larger P300 amplitudes. There were no statistically significant changes in the electrophysiological parameters of CERPs in patients with pSS dependent on the presence of peripheral nervous system (PNS) lesions, skin changes, arthritis, abnormalities in white blood cells and the immune system or the levels of blood lipids. CONCLUSIONS: The results of the study suggest the presence of a minor cognitive dysfunction in patients with pSS without symptoms of CNS involvement or mental disorder. Cognitive dysfunction correlated with the disease duration time and the severity of inflammatory changes (salivary gland abnormalities and inflammatory markers in the blood). Further and larger longitudinal studies are necessary for confirmation of this correlation. PMID- 26271274 TI - Remogliflozin etabonate : a novel SGLT2 inhibitor for treatment of diabetes mellitus. AB - INTRODUCTION: Inhibitors of sodium-glucose co-transporter type 2 (SGLT2) represent a new class of anti-hyperglycemic agents with a unique mechanism of action. These drugs lower blood glucose by increasing urinary glucose excretion. Remogliflozin etabonate (RE) is a prodrug of remogliflozin, an SGLT2 inhibitor under development. Areas covered: The following article reviews all of the clinical studies published regarding metabolism, drug interaction, safety and efficacy of RE in healthy subjects, patients with type 1 and type 2 diabetes. Expert opinion: Available data suggest low potential for RE to interact with other drugs affecting the P450 system. Compared with placebo, RE reduces hemoglobin A1c (HbA1c) levels by an average of 0.5 - 1.0% after 12 weeks of therapy in drug-naive patients with type 2 diabetes. Because of its relatively short half-life, RE may be slightly more effective when used twice daily than once daily. One preliminary study also showed that RE decreased plasma glucose levels in type 1 diabetes. Advantages of RE include modest weight loss of ~ 2 kg, low risk of hypoglycemia, and a trend toward decrease in blood pressure. The commonest adverse effects of RE are genital mycotic infections, urinary tract infections, and dizziness. However, further studies are needed to establish its long-term safety and efficacy, and to determine whether it has specific advantages over currently approved SGLT2 inhibitors. PMID- 26271273 TI - Higher Incidence of Hypospadias in Monochorionic Twins. AB - BACKGROUND: Hypospadias is associated with twinning. The incidence of hypospadias in monochorionic and dichorionic male twins is, however, yet to be determined. METHODS: All medical records of monochorionic and dichorionic twins admitted to our neonatal nursery between January 2004 and August 2013 were reviewed for the presence of hypospadias. RESULTS: A total of 350 monochorionic and 303 dichorionic male twins were included in the study. The incidence of hypospadias in monochorionic and dichorionic groups was 4% (14/350) and 1% (3/303) (p = .016) respectively. In 11 of the 15 twin couples, hypospadias occurred in the twin with the lowest birth weight. The rate of hypospadias in twin infants small-for gestational-age group was 10% (6/60) compared with 2% (11/593) in the appropriate for-gestational-age group (p = .002). In a multivariate analysis, both monochorionicity and small-for-gestational-age were independently associated with hypospadias, odds ratio 4.1 (95% confidence interval (CI): 1.1-14.7) and 6.1 (95% CI: 2.2-17.2) respectively. CONCLUSIONS: The incidence of hypospadias is four fold higher in monochorionic twins compared with dichorionic twins. Hypospadias is also independently associated with small-for-gestational-age. PMID- 26271275 TI - Effect of Sugammadex on Postoperative Bleeding and Coagulation Parameters After Septoplasty: A Randomized Prospective Study. AB - BACKGROUND: Sugammadex is a reversal agent with well known advantages but it's effects on haemostasis and bleeding have been a topic of interest. Septoplasty is a common surgical procedure with postoperative respiratory complications and bleeding. The aim of this study is to investigate the effects of sugammadex on postoperative coagulation parameters and bleeding after septoplasty procedure. MATERIAL AND METHODS: In this randomized controlled study, fifty patients were grouped into two groups; neostigmine (Group N) vs. sugammadex (Group S). For the evaluation of PT, aPTT and INR, blood samples were taken for at the postoperative 120th minutes and alteration of these values with respect to preoperative values were documented. Postoperative bleeding was measured by evaluating the amount of blood absorbed on the nasal tip dressing during 3 hours postoperatively. RESULTS: Postoperative bleeding amount was significantly higher in the Group S compared to Group N (p=0.013). No significant difference was observed between two groups according to coagulation parameters (PT; p=0.953, aPTT; p=0.734, INR; p=0.612). CONCLUSIONS: Sugammadex was associated with higher amount of postoperative bleeding than neostigmine in septoplasty patients. In surgical procedures having high risk of bleeding the safety of sugammadex need to be verified. PMID- 26271276 TI - Frontal facial proportions of 12-year-old southern Chinese: a photogrammetric study. AB - This study aimed to establish norm values for facial proportion indices among 12 year-old southern Chinese children, to determine lower facial proportion, and to identify gender differences in facial proportions.A random population sample of 514 children was recruited. Fifteen facial landmarks were plotted with ImageJ (V1.45) on standardized photos and 22 Facial proportion index values were obtained. Gender differences were analyzed by 2-sample t-test with 95% confidence interval. Repeated measurements were conducted on approximately 10% of the cases.The rate of adopted subjects was 52.5% (270/514). Intraclass correlation coefficient values (ICC) for intra- examiner reliability were >0.87. Population facial proportion index values were derived. Gender differences in 11 of the facial proportion indices were evident (P < 0.05).Upper face-face height (N- Sto/ N- Gn), vermilion height (Ls-Sto/Sto-Li), upper face height-biocular width (N Sto/ExR-ExL) and nose -face height (N-Sn/N-Gn) indices were found to be larger among girls (P < 0.01). Males had larger lower face-face height (Sn -Gn/ N-Gn), mandibulo-face height (Sto-Gn/N-Gn), mandibulo-upper face height (Sto-Gn/N-Sto), nasal (AlR-AlL/N-Sn), upper lip height-mouth width (Sn-Sto/ChR-ChL), upper lip upper face height (Sn-Sto/N-Sto) and upper lip-nose height (Sn-Sto/N-Sn) indices (P < 0.05).Population norm of facial proportion indices for 12-year-old Southern Chinese were derived and mean lower facial proportion were obtained. Sexual dimorphism is apparent. PMID- 26271277 TI - Molecular species identification, host preference and detection of myxoma virus in the Anopheles maculipennis complex (Diptera: Culicidae) in southern England, UK. AB - BACKGROUND: Determining the host feeding patterns of mosquitoes by identifying the origin of their blood-meals is an important part of understanding the role of vector species in current and future disease transmission cycles. Collecting large numbers of blood-fed mosquitoes from the field is difficult, therefore it is important to maximise the information obtained from each specimen. This study aimed to use mosquito genome sequence to identify the species within Anopheles maculipennis sensu lato (An. maculipennis s.l.), identify the vertebrate hosts of field-caught blood-fed An. maculipennis s.l. , and to test for the presence of myxoma virus (Poxviridae, genus Leporipoxvirus) in specimens found to have fed on the European rabbit (Oryctolagus cuniculus). METHODS: Blood-fed An. maculipennis s.l. were collected from resting sites at Elmley Nature Reserve, Kent, between June and September 2013. Hosts that An. maculipennis s.l. had fed on were determined by a PCR-sequencing approach based on the partial amplification of the mitochondrial cytochrome C oxidase subunit I gene. Mosquitoes were then identified to species by sequencing a region of the internal transcribed spacer 2. DNA extracts from all mosquitoes identified as having fed on rabbits were subsequently screened using PCR for the presence of myxoma virus. RESULTS: A total of 94 blood-fed Anopheles maculipennis s.l. were collected, of which 43 (46%) provided positive blood-meal identification results. Thirty-six of these specimens were identified as Anopheles atroparvus, which had fed on rabbit (n = 33, 92%) and cattle (n = 3, 8%). Seven mosquitoes were identified as Anopheles messeae, which had fed on cattle (n = 6, 86%) and dog (n = 1, 14%). Of the 33 An. atroparvus that contained rabbit blood, nine (27%) were positive for myxoma virus. CONCLUSIONS: Results demonstrate that a single DNA extract from a blood fed mosquito can be successfully used for molecular identification of members of the An. maculipennis complex, blood-meal identification, and for the targeted detection of a myxoma virus. This study shows that An. atroparvus has a strong feeding preference for both healthy and myxoma-infected rabbits, providing evidence that this species may play a significant role in the transmission of myxomatosis among wild rabbit populations in the United Kingdom (UK). PMID- 26271278 TI - Gallbladder perforation: a rare complication of postoperative chemotherapy of gastric cancer. AB - A middle-aged man presented 1 day after being discharged from hospital with completing the first course of postoperative chemotherapy. He suffered a sudden persistent high fever and chills. It was noted that he had a history of a total gastrectomy (with D2 lymphadenectomy) 1 month ago. His admission bloods revealed total bilirubin was 142.2 umol/L, indirect bilirubin of 107.6 umol/L and white cell count of 20.05*10(9)/L. A color doppler ultrasound scan confirmed fluid and gas around liver and hilus lienis while the gallbladder cannot be detected. During Computed Tomography (CT) guided puncture positioning technology and setting a three-channel tube, about 400 ml of foul smell hazel turbid liquid was drained out. He was diagnosed as gallbladder perforation and he was underwent conservative treatment consist of drainage, banning diet, total parenteral nutrition and intravenous antibiotics. Then he recovered well within the subsequent 10 days and was discharged. PMID- 26271279 TI - Stauntonia hexaphylla (Lardizabalaceae) leaf methanol extract inhibits osteoclastogenesis and bone resorption activity via proteasome-mediated degradation of c-Fos protein and suppression of NFATc1 expression. AB - BACKGROUND: Natural plants, including common vegetables and fruits, have been recognized as essential sources for drug discovery and the development of new, safe, and economical medicaments. Stauntonia hexaphylla (Lardizabalaceae) is widely distributed in Korea, Japan, and China, and is a popular herbal supplement in Korean and Chinese folk medicine owing to its analgesic, sedative, and diuretic properties. However, the exact pharmacological effects of S. hexaphylla extract, particularly its effect on osteoclastogenesis, are not known. METHODS: Osteoclast differentiation and function were identified with tartrate-resistant acid phosphatase (TRAP) staining and bone resorption assay, and the underling mechanisms were determined by real-time RT-PCR and western blot analysis. RESULTS: S. hexaphylla was found to inhibit early-stage receptor activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL)-mediated osteoclast differentiation in bone marrow macrophages (BMMs) without cytotoxicity and bone resorbing activity in mature osteoclasts in a dose-dependent manner. This S. hexaphylla-mediated blockade of osteoclastogenesis involved abrogation of the NF kappaB, ERK, and c-Src-Btk-PLCgamma2 calcium signal pathways. Interestingly, we found that S. hexaphylla down-regulated RANKL-associated c-Fos protein induction by suppressing its translation. Furthermore, ectopic overexpression of c-Fos and NFATc1 rescued the inhibition of osteoclast differentiation by S. hexaphylla. Furthermore, S. hexaphylla inhibited the c-Fos- and NFATc1-regulated expression of genes required for osteoclastogenesis, such as TRAP, OSCAR, beta3-integrin, ATP6v0d2, and CtsK. CONCLUSIONS: These findings suggest that S. hexaphylla might be useful for the development of new anti-osteoporosis agents. PMID- 26271280 TI - Development of the Perinatal Depression Inventory (PDI)-14 using item response theory: a comparison of the BDI-II, EPDS, PDI, and PHQ-9. AB - The objective of this study is to develop a simple, brief, self-report perinatal depression inventory that accurately measures severity in a number of populations. Our team developed 159 Likert-scale perinatal depression items using simple sentences with a fifth-grade reading level. Based on iterative cognitive interviewing (CI), an expert panel improved and winnowed the item pool based on pre-determined criteria. The resulting 67 items were administered to a sample of 628 pregnant and 251 postpartum women with different levels of depression at private and public sector obstetrics clinics, together with the Beck Depression Inventory (BDI-II), Edinburg Postpartum Depression Scale (EPDS), and the Patient Health Questionnaire (PHQ-9), as well as Module A of the Structured Clinical Interview for DSM-IV Diagnoses (SCID). Responses were evaluated using Item Response Theory (IRT). The Perinatal Depression Inventory (PDI)-14 items are highly informative regarding depression severity and function similarly and informatively across pregnant/postpartum, white/non-white, and private clinic/public-clinic populations. PDI-14 scores correlate well with the PHQ-9, EPDS, and BDI-II, but the PDI-14 provides a more precise measure of severity using far fewer words. The PDI-14 is a brief depression assessment that excels at accurately measuring depression severity across a wide range of severity and perinatal populations. PMID- 26271281 TI - Maternal depression from pregnancy to 4 years postpartum and emotional/behavioural difficulties in children: results from a prospective pregnancy cohort study. AB - Considerable attention has been focused on women's mental health in the perinatal period and the subsequent impacts on children. Comparatively, we know much less about maternal depression at later time points and the potential implications for child mental health. The objective of this paper was to explore the association between maternal depression and child emotional/behavioural difficulties at 4 years postpartum, taking into account earlier episodes of perinatal depression. The Maternal Health Study is a prospective cohort study of 1,507 nulliparous women. Maternal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS) in early pregnancy and at 3, 6 and 12 months postpartum and again at 4 years postpartum. Maternal depressive symptoms at 4 years postpartum were associated with significantly increased odds of child emotional/behavioural difficulties (odds ratio (OR) = 3.46, 95 % confidence interval (CI) = 2.21-5.43). This remained significant after adjusting for earlier episodes of perinatal depression and socio-demographic characteristics (OR = 2.07, 95 % CI = 1.18-3.63). We also observed a robust association between child difficulties at age 4 and measures of socio-economic disadvantage. Our findings suggest a pressing need to rethink current paradigms of maternal health surveillance and extend mental health surveillance and support to at least 4 years postpartum. PMID- 26271282 TI - A new outbreak of fox rabies at the Russian-Mongolian border. PMID- 26271283 TI - Construction and characterization of infectious cDNA clones of enterovirus 71 (EV71). PMID- 26271284 TI - Detection of seed DNA in regurgitates of granivorous carabid beetles. AB - Granivory can play a pivotal role in influencing regeneration, colonization as well as abundance and distribution of plants. Due to their high abundance, nutrient content and longevity, seeds are an important food source for many animals. Among insects, carabid beetles consume substantial numbers of seeds and are thought to be responsible for a significant amount of seed loss. However, the processes that govern which seeds are eaten and are therefore prevented from entering the seedbank are poorly understood. Here, we assess if DNA-based diet analysis allows tracking the consumption of seeds by carabids. Adult individuals of Harpalus rufipes were fed with seeds of Taraxacum officinale and Lolium perenne allowing them to digest for up to 3 days. Regurgitates were tested for the DNA of ingested seeds at eight different time points post-feeding using general and species-specific plant primers. The detection of seed DNA decreased with digestion time for both seed species, albeit in a species-specific manner. Significant differences in overall DNA detection rates were found with the general plant primers but not with the species-specific primers. This can have implications for the interpretation of trophic data derived from next-generation sequencing, which is based on the application of general primers. Our findings demonstrate that seed predation by carabids can be tracked, molecularly, on a species-specific level, providing a new way to unravel the mechanisms underlying in-field diet choice in granivores. PMID- 26271285 TI - Air pocket stability and the imbibition pathway in droplet wetting. AB - The stability of air pockets formed in grooves on a surface is relevant to contact angle hysteresis of droplet wetting and it is investigated by imbibition experiments and surface evolver (SE) simulations. Liquid drops of different wettabilities are placed atop a conical hole on a polymethyl methacrylate (PMMA) substrate. The stability of the air pocket depends on surface wettability. Four kinds of imbibition behaviors ranging from wetting to nonwetting are observed. The imbibition pathway for the kinetically unstable air pocket is observed by using the olive oil droplet. It involves an inward flow of a thin liquid film along the wall of the hole. The accumulation of liquid at the bottom leads to the rise of the air bubble. The energy-barrier profile associated with the imbibition pathway acquired by SE simulations is able to interpret the outcome of imbibition. The advancing and receding contact angles of various liquids on a PMMA substrate with drilled holes are also determined. Their wetting behaviors can be categorized into three types. Our experimental results for substrates with or without fluorination are in good agreement with the theory based on the stability of air pockets. PMID- 26271286 TI - Erratum to: Predator interference alters foraging behavior of a generalist predatory arthropod. PMID- 26271287 TI - Distribution, behavior, and condition of herbivorous fishes on coral reefs track algal resources. AB - Herbivore distribution can impact community structure and ecosystem function. On coral reefs, herbivores are thought to play an important role in promoting coral dominance, but how they are distributed relative to algae is not well known. Here, we evaluated whether the distribution, behavior, and condition of herbivorous fishes correlated with algal resource availability at six sites in the back reef environment of Moorea, French Polynesia. Specifically, we tested the hypotheses that increased algal turf availability would coincide with (1) increased biomass, (2) altered foraging behavior, and (3) increased energy reserves of herbivorous fishes. Fish biomass and algal cover were visually estimated along underwater transects; behavior of herbivorous fishes was quantified by observations of focal individuals; fish were collected to assess their condition; and algal turf production rates were measured on standardized tiles. The best predictor of herbivorous fish biomass was algal turf production, with fish biomass increasing with algal production. Biomass of herbivorous fishes was also negatively related to sea urchin density, suggesting competition for limited resources. Regression models including both algal turf production and urchin density explained 94 % of the variation in herbivorous fish biomass among sites spread over ~20 km. Behavioral observations of the parrotfish Chlorurus sordidus revealed that foraging area increased as algal turf cover decreased. Additionally, energy reserves increased with algal turf production, but declined with herbivorous fish density, implying that algal turf is a limited resource for this species. Our findings support the hypothesis that herbivorous fishes can spatially track algal resources on coral reefs. PMID- 26271289 TI - Hydrogen-bonding interactions of uric acid complexes with water/melamine by mid infrared spectroscopy. AB - Hydrogen (H)-bonding interactions of uric acid (UA) with water have been investigated via IR-UV double resonance measurements in the mid-IR region. Comparison of the present results with those obtained previously in the near-IR region enables us to examine microscopic hydration effects that are specific to the H-bonding acceptor sites of UA. It is shown that hydration of the C8O site promotes the mode coupling of this stretch with the C2O stretch. The occurrence of this coupling is manifested in the IR intensity pattern, in which the transition associated with the in-phase contribution C8O + C2O is significantly suppressed, whereas the corresponding out-of-phase contribution gives rise to a strong peak. We also measured the mid-IR spectra of the 1 : 1 complex formed between UA and melamine (MEL) and carried out a structural analysis using the spectroscopic signature of the H-bonding derived from the result of the monohydrated cluster. It is shown that the complex possesses a triple H-bonding structure with the C2O acceptor site of UA H-bonded to MEL. Furthermore, the IR depleted UV spectroscopy technique was employed in order to ascertain whether other structural isomers are present in the probe UV spectra. PMID- 26271288 TI - beta-Asarone Mitigates Amyloidosis and Downregulates RAGE in a Transgenic Mouse Model of Alzheimer's Disease. AB - Elevated beta-amyloid (Abeta) is a hallmark of Alzheimer's disease (AD). Recent evidence has suggested that the receptor of advanced glycation end products (RAGE) is a key target for Abeta-induced perturbation in AD, and blockade of RAGE significantly alleviates synaptic injury. Our previous study has suggested that beta-asarone could reduce neuronal apoptosis and improve memory deficits in beta amyloid precursor protein and presenilin-1 (APP/PS1) double transgenic AD-model mice. In the present study, we evaluated the effects of beta-asarone on amyloidosis in APP/PS1 mice. We found that the survival of neurons of APP/PS1 mice was improved by beta-asarone, meanwhile, beta-asarone decreased Abeta deposition and down-regulated Abeta1-42 levels in cortex and hippocampus of APP/PS1 mice brain. Interestingly, the level of RAGE was also significantly down regulated by beta-asarone. Our findings suggest that beta-asarone might be effective for the treatment of AD, and the decreasing effects of beta-asarone on Abeta might associate with its down-regulation of RAGE. PMID- 26271290 TI - [Comments on the PREFERE study]. PMID- 26271291 TI - Robotic distal pancreatectomy versus conventional laparoscopic distal pancreatectomy: a comparative study for short-term outcomes. AB - Robotic system has been increasingly used in pancreatectomy. However, the effectiveness of this method remains uncertain. This study compared the surgical outcomes between robot-assisted laparoscopic distal pancreatectomy and conventional laparoscopic distal pancreatectomy. During a 15-year period, 35 patients underwent minimally invasive approach of distal pancreatectomy in our center. Seventeen of these patients had robot-assisted laparoscopic approach, and the remaining 18 had conventional laparoscopic approach. Their operative parameters and perioperative outcomes were analyzed retrospectively in a prospective database. The mean operating time in the robotic group (221.4 min) was significantly longer than that in the laparoscopic group (173.6 min) (P = 0.026). Both robotic and conventional laparoscopic groups presented no significant difference in spleen-preservation rate (52.9% vs. 38.9%) (P = 0.505), operative blood loss (100.3 ml vs. 268.3 ml) (P = 0.29), overall morbidity rate (47.1% vs. 38.9%) (P = 0.73), and post-operative hospital stay (11.4 days vs. 14.2 days) (P = 0.46). Both groups also showed no perioperative mortality. Similar outcomes were observed in robotic distal pancreatectomy and conventional laparoscopic approach. However, robotic approach tended to have the advantages of less blood loss and shorter hospital stay. Further studies are necessary to determine the clinical position of robotic distal pancreatectomy. PMID- 26271292 TI - Small cell carcinoma of the urinary bladder without gross hematuria: a case report. AB - Small cell carcinoma of the urinary bladder (SCCB) is a rare and aggressive form of bladder cancer with poor prognosis. Hematuria is the main symptom of this malignancy, and most patients have a history of smoking. The disease incidence of malignant bladder tumors in China is approximately 0.74%. Early and accurate diagnosis of SCCB can ensure timely and appropriate treatment of this malignant disease. Oncologic surgery is the standard treatment; however, it may not be a curative approach. Chemotherapy and/or radiotherapy should be performed following surgical removal. This case report describes a patient with a single neoplasm diagnosed as SCCB that arose because of recurrence of bladder cancer after bladder tumor resection. In contrast to previously reported cases, this patient had no gross hematuria and no history of smoking. PMID- 26271293 TI - Cushing's syndrome during pregnancy caused by adrenal cortical adenoma: a case report and literature review. AB - Cushing's syndrome (CS) during pregnancy is a rare condition with significant maternal and fetal complications. A case of CS during the third trimester of pregnancy secondary to adrenocortical adenoma was reported. Literature review revealed the disadvantages of different treatments in this period. Besides the conservative treatment, surgery is recommended for CS during the third trimester of pregnancy secondary to adrenal adenoma, if an experienced surgeon is available. PMID- 26271294 TI - Tendinopathy after ofloxacin ear drops. PMID- 26271296 TI - Comments of Environmental Conditions for the Maintenance of Leptospira in Tropical Scenarios. PMID- 26271295 TI - Plant Pathogenic Microbial Communication Affected by Elevated Temperature in Pectobacterium carotovorum subsp. carotovorum. AB - Gram-negative plant pathogenic bacteria regulate specific gene expression in a population density-dependent manner by sensing level of Acyl-Homoserine Lactone (HSL) molecules which they produce and liberate to the environment, called Quorum Sensing (QS). The production of virulence factors (extracellular enzyme viz. cellulase, pectinase, etc.) in Pectobacterium carotovorum subsp. carotovorum (Pcc) is under strong regulation of QS. The QS signal molecule, N-(3-oxohexanoyl) L-Homoserine Lactone (OHHL) was found as the central regulatory system for the virulence factor production in Pcc and is also under strict regulation of external environmental temperature. Under seven different incubation temperatures (24, 26, 28, 30, 33, 35, and 37 degrees C) in laboratory condition, highest amount of OHHL (804 violacein unit) and highest (79 %) Disease Severity Index (DSI) were measured at 33 degrees C. The OHHL production kinetics showed accumulation of highest concentration of OHHL at late log phase of the growth but diminution in the concentration occurred during stationary phase onwards to death phase. At higher temperature (35 and 37 degrees C) exposure, OHHL was not at detectable range. The effect of temperature on virulence factor production is the concomitant effect of HSL production and degradation which justifies less disease severity index in cross-inoculated tomato fruits incubated at 35 and 37 degrees C. The nondetection of the OHHL in the elevated temperature may because of degradation as these signal molecules are quite sensitive and prone to get degraded under different physical factors. This result provides the rationale behind the highest disease severity up to certain elevated temperature and leaves opportunities for investigation on mutation, co-evolution of superior plant pathogen with more stable HSL signals-mediated pathogenesis under global warming context. PMID- 26271297 TI - Characterization and Genome Sequencing of a Novel Bacteriophage PH101 Infecting Pseudoalteromonas marina BH101 from the Yellow Sea of China. AB - A novel Pseudoalteromonas marina bacteriophage, PH101, specifically infecting Pseudoalteromonas BH101 was isolated from the water sample of the Yellow Sea of China using the agar overlay method. 16S rDNA sequence identification was used to identify the host bacteria. Efficiency of infection, multiplicity of infection value, morphological characterization, one-step growth curve, and host range of the bacteriophage were determined. Purified PH101 genomic DNA was extracted and its genome was completely sequenced and analyzed. The phage morphology showed that PH101 belongs to the Myoviridae family with a head of 60 nm in diameter and a tail of 40 nm with a tail fiber of 10-20 nm. Microbiological characterization demonstrated that phage PH101 is stable at a wide range of temperatures (0-70 degrees C) and showed acid and alkaline resistance (pH 3-12). The one-step growth curve showed a latent period of about 20 min, a rise period of 20 min, and a burst size of about 31.6 virions. The genome sequencing and bioinformatic analysis shows that phage PH101 was a novel bacteriophage which was found to consist of a linear, double-stranded 131,903-bp DNA molecule with a GC content of 37.36 % and 228 putative open reading frames without RNA, which were classified into seven functional groups, including phage structure, adsorption, packaging, gene transfer protease, terminase, DNA binding, and regulation. PMID- 26271298 TI - The on-surface synthesis of imine-based covalent organic frameworks with non aromatic linkage. AB - A pair of isomeric imine-based covalent organic frameworks with non-aromatic linkage has been fabricated at the graphite surface, which extends the structural diversity of surface covalent organic frameworks. PMID- 26271299 TI - Feasibility and Reliability of a Coding System to Capture In-Session Group Behavior in Adolescents. AB - Limited research has explored the role of in-session behavior during motivational enhancement (ME) in group formats. The current study presents initial feasibility of assessing behavior of high school students (N = 425) attending Project Options, a voluntary secondary drug and alcohol prevention program utilizing ME techniques. Building on previous research exploring client language supporting/opposing health behavior, student group behavior was coded live at the specific utterance and global level; group leader behavior was also coded globally. Interrater reliability of the coding system was assessed, and preliminary validity of the coding system was examined by exploring associations between characteristics of group members and in-session group behavior. Initial reliability estimates were excellent for the specific behavior codes. Reliability of the global codes was mixed, with raters demonstrating good reliability on support for unhealthy behavior, opposition to unhealthy behavior, and support for healthy behavior. Reliability of the group leader codes was fair to poor. Greater percent healthy talk was associated with a lower percentage of group members reporting lifetime alcohol use. The results of the current study suggest that some in-session behavior at the group level can be coded reliably via live observation and that in-session behavior at the group level is associated with alcohol use prior to attending the program. Future research is needed to explore the utility of in-session behavior in terms of predicting future behavior at the group and individual level. PMID- 26271300 TI - An Experimental Study of Procedures to Enhance Ratings of Fidelity to an Evidence Based Family Intervention. AB - The valid and reliable assessment of fidelity is critical at all stages of intervention research and is particularly germane to interpreting the results of efficacy and implementation trials. Ratings of protocol adherence typically are reliable, but ratings of therapist competence are plagued by low reliability. Because family context and case conceptualization guide the therapist's delivery of interventions, the reliability of fidelity ratings might be improved if the coder is privy to client context in the form of an ecological assessment. We conducted a randomized experiment to test this hypothesis. A subsample of 46 families with 5-year-old children from a multisite randomized trial who participated in the feedback session of the Family Check-Up (FCU) intervention were selected. We randomly assigned FCU feedback sessions to be rated for fidelity to the protocol using the COACH rating system either after the coder reviewed the results of a recent ecological assessment or had not. Inter-rater reliability estimates of fidelity ratings were meaningfully higher for the assessment information condition compared to the no-information condition. Importantly, the reliability of the COACH mean score was found to be statistically significantly higher in the information condition. These findings suggest that the reliability of observational ratings of fidelity, particularly when the competence or quality of delivery is considered, could be improved by providing assessment data to the coders. Our findings might be most applicable to assessment-driven interventions, where assessment data explicitly guides therapist's selection of intervention strategies tailored to the family's context and needs, but they could also apply to other intervention programs and observational coding of context-dependent therapy processes, such as the working alliance. PMID- 26271301 TI - Quality of life predictors in chronic stable post-stroke patients and prognostic value of SF-36 score as a mortality surrogate. AB - Perceived quality of life (QoL) and psychological well-being represents an important target of secondary prevention practice in post-stroke patients. We aimed to identify the major covariates of impaired QoL in stable post-stroke patients and whether impaired QoL itself represents independent mortality predictor.The study consisted of a cross-sectional and a prospective part. Three hundred forty-one patients [mean age 69.0 (SD 9.1)] were interviewed at least 6 months after discharge from hospital for their first-ever ischemic stroke. QoL was objectivized using 36-Item Short-Form Health Survey (SF-36) scoring. Standard health-related questionnaires, including Hospital Anxiety and Depression Scale (HADS), risk factors, and biochemical markers, were assessed. To estimate the 5 year all-cause and cardiovascular mortality, we ascertained the vital status and declared cause of death.Anxiety, depression (HADS score >=11), brain natriuretic peptide levels >=100 ng/mL, residual motor impairment at interview, Rankin Scale >=4 at discharge from hospitalization, and raised blood pressure were identified as main determinants of impaired QoL in the cross-sectional part. The 5-year all cause and cardiovascular mortality rates were 25.8 and 19.9 %, respectively. After adjustment for potential covariates, patients with an SF-36 score <=40 at baseline had more than a twofold higher risk of all-cause and cardiovascular mortality (with HRRs 2.01 (95 % CI 1.21-3.32), p < 0.007 and 2.32 (95 % CI 1.32 4.09), p < 0.003, respectively) during the 5 years of follow-up.In conclusion, anxiety, depression, and raised brain natriuretic peptide levels were the most important covariates of impaired QoL in post-stroke patients. Moreover, a decreased SF-36 score (<=40) represents an independent surrogate of increased additive mortality risk. PMID- 26271302 TI - (13)CHD2-CEST NMR spectroscopy provides an avenue for studies of conformational exchange in high molecular weight proteins. AB - An NMR experiment for quantifying slow (millisecond) time-scale exchange processes involving the interconversion between visible ground state and invisible, conformationally excited state conformers is presented. The approach exploits chemical exchange saturation transfer (CEST) and makes use of (13)CHD2 methyl group probes that can be readily incorporated into otherwise highly deuterated proteins. The methodology is validated with an application to a G48A Fyn SH3 domain that exchanges between a folded conformation and a sparsely populated and transiently formed unfolded ensemble. Experiments on a number of different protein systems, including a 360 kDa half-proteasome, establish that the sensitivity of this (13)CHD2 (13)C-CEST technique can be upwards of a factor of 5 times higher than for a previously published (13)CH3 (13)C-CEST approach (Bouvignies and Kay in J Biomol NMR 53:303-310, 2012), suggesting that the methodology will be powerful for studies of conformational exchange in high molecular weight proteins. PMID- 26271304 TI - Evaluation of the retinal, choroidal, and nerve fiber layer thickness changes in patients with toxic anterior segment syndrome. PMID- 26271303 TI - Comparison of refractive outcomes in three corneal transplantation techniques for keratoconus. AB - BACKGROUND: Deep anterior lamellar keratoplasty (DALK) has a much lower incidence of immunologic reactions than penetrating keratoplasty (PK) for patients with keratoconus. However, it is unclear whether DALK is better on refractive outcomes than PK, due to its high postoperative myopia. METHODS: We retrospectively studied the clinical records of keratoconus patients who underwent PK, DALK, or predescemetic DALK (pre-DALK, DALK with residual stroma) between June 2004 and September 2008. The main outcome measures included refractive sphere, manifest cylinder, corneal power, keratometric astigmatism, and best-corrected visual acuity (BCVA) at the latest visit and the methods of visual correction. Postoperative manifest refractions and topography data were compared at postoperative 3, 5, 7, and 9 years among the three groups. Additionally, the final BCVA and the methods of vision correction were compared. RESULTS: A total of 172 subjects (172 eyes) screened out of 207 keratoconus patients underwent PK (79 eyes), DALK (68 eyes), or pre-DALK (25 eyes). Postoperative myopic refractive sphere increased in all groups, but the most obvious increase was noted in the pre-DALK group. At the 9-year follow-up, both the pre-DALK group (-6.5 +/- 1.7 D) and DALK group (-6.1 +/- 1.8 D) had higher myopic refractive sphere than the PK group (-5.0 +/- 1.5 D, p < 0.05). Postoperative myopic manifest astigmatism progressively increased in 5 years, but there were no differences among the groups. The progressive increases in postoperative corneal power were recorded in all groups, with the highest one in the pre-DALK group and the lowest in the PK group. At the 9-year follow-up, both the pre-DALK (49.8 +/- 2.7 D) and DALK (48.8 +/- 2.1 D) groups had higher corneal power than the PK group (47.3 +/- 2.0 D); meanwhile, the corneal power was higher in the pre-DALK group than the DALK group (p < 0.05). No differences were noted with respect to keratometric astigmatism among the groups. Mean LogMAR BCVA was 0.12 +/- 0.12 in the DALK group, 0.17 +/- 0.10 in the pre-DALK group, and 0.1 +/- 0.11 in the PK group (p = 0.325) at 9 years after surgery. Moreover, the methods of achieving BCVA seem to be similar among the treatment groups. CONCLUSIONS: Although DALK has a slightly higher degree of myopic refraction than PK, DALK and PK have comparable visual acuity outcomes and similar methods of vision correction. DALK is recommended for the treatment of keratoconus. PMID- 26271305 TI - Heavy Metal Dietary Intake and Potential Health Risks for University Hostel Students. AB - The study was conducted to determine the residual concentration of Cd, Pb, Asand Hg in some foodstuffs served to university students living at hostels of Beni Suef University (BSU), Egypt, and to estimate the dietary intake of such metals, as well as to assess the potential health risks associated with the consumption of such foods. Therefore, a total of 200 samples, 50 each of, soft cheese, UHT milk, raw broiler carcasses and canned tuna, were periodically collected from university hostels of BSU and examined for the residual levels of these metals using atomic absorption spectrophotometer. The obtained results revealed that the mean residual levels of Cd in soft cheese, UHT milk, broiler's meat and canned tuna samples were 0.37, 0.26, 0.089 and 0.093 mg/kg, respectively, while those of Pb were 0.187, 0.20, 0.181 and 0.164 mg/kg, respectively. Regarding As, they were 0.196, 0.24, 0.14 and 0.201 mg/kg, respectively, and Hg mean residual concentration accounted for 0.05, 0.05, 0.117 and 0.235 mg/kg, respectively. Some of the examined food samples had heavy metals' concentrations above the international standards. The total weekly dietary intakes of Cd, Pb, As and Hg were 4.99, 5.38, 4.77 and 2.76 MUg/kg bw/week, respectively, that were comparable to the provisional tolerable weekly intake recommended by the Joint Expert Committee on Food Additives (JECFA). The total target hazard quotient (TTHQ) of broiler's meat was over 1 (1.686), thus indicating possible health risks in contrast to the TTHQs of other foodstuffs that were below one. PMID- 26271306 TI - ZnO Nanoparticles Upregulates Adipocyte Differentiation in 3T3-L1 Cells. AB - The present study was aimed to investigate the effect of zinc oxide (ZnO) nanoparticles on 3T3-L1 cell differentiation, by quantitating peroxisome proliferators-activated receptor gamma (PPARgamma), CCAAT/enhancer binding protein alpha (C/EBPalpha), fatty acid binding protein 4 (FABP4), sterol regulatory element-binding transcription factor 1 (SREBP1), and serine-threonine kinase cyclin-dependent kinase 4 (cdk4), which are critical for adipogenesis. 3T3 L1 preadipocyte cells were cultured and differentiated with the standard differentiation medium. Sulforhodamine B (SRB) assay determined 3T3-L1 cell viability. ZnO nanoparticles increased the lipid accumulation in differentiated adipocytes as evidenced by Oil Red O staining. The quantitative PCR (qPCR) analysis showed that the PPARgamma, FABP4, C/EBPalpha, and SREBP1 messenger RNA (mRNA) expression was significantly increased in the ZnO nanoparticle-treated 3T3 L1 adipocytes. Western blot analysis showed increased PPARgamma, FABP4, C/EBPalpha, and SREBP1 protein expression compared to their respective controls. Also, the immunofluorescence study showed the increased cdk4 and PPARgamma expression in the nanoparticle-treated cells. Taking all these data together, it is concluded that ZnO nanoparticles may be a potent substance to alter 3T3-L1 preadipocyte differentiation and adipogenesis. PMID- 26271307 TI - Correlation Analysis of Exercise-Induced Changes in Plasma Trace Element and Hormone Levels During Incremental Exercise in Well-Trained Athletes. AB - This study analyzes the relationship between hormonal changes induced by exercise and variations in trace elements associated with oxidative stress during incremental exercise. Nineteen well-trained endurance athletes performed a cycle ergometer test: after a warm-up of 10 min at 2.0 W kg(-1), workload increased by 0.5 W kg(-1) every 10 min until exhaustion. The analysis was controlled for prior diet and activity patterns, levels of exercise training, and time of day (circadian rhythms). Whole blood lactate concentration and plasma concentrations of ions (Zn, Se, Mn, and Co), insulin, glucagon, aldosterone, thyroid stimulating hormone (TSH), calcitonin, and parathyroid hormone (PTH) were measured at rest; at the end of each stage; and 3, 5, and 7 min post-exercise. The statistical analysis involved paired non-parametric tests and correlation coefficients. No significant differences were found in Mn or Co levels as a function of exercise intensity. Zn and Se levels at the end of the exercise protocol and over the recovery time were significantly different to baseline. Further, Zn levels were significantly correlated with aldosterone, calcitonin, and PTH levels, while Se levels were associated with aldosterone, calcitonin, and TSH levels. Our results indicate several different patterns of association between acute changes in hormone concentrations and variations in trace element concentrations related to oxidative stress during submaximal exercise. PMID- 26271308 TI - The search for optimal anticoagulation therapy in ACS: The gap between clinical trials and current clinical guidelines. PMID- 26271309 TI - Spatial conception of activities: a socio-cognitive perspective for simulating work practices. AB - People conceive their everyday affairs (their practices) as social actors in activities, in which they perceive, infer, move, manipulate objects, and communicate in some physical setting (e.g., going to the grocery to buy dinner). These behaviors are conceptually choreographed in an ongoing, usually tacit understanding of "what I'm doing now," encapsulating roles ("who I'm being now"), norms ("what I should be doing"; "how I should be dressed/talking/sitting"), and progress appraisals ("how well I'm doing"). Activity motives and modalities vary widely (e.g., waiting in line, listening to music, sleeping), all of which require time and occur in particular settings. Brahms is a multi-agent work systems design tool for modeling and simulating activities, used extensively to design aerospace work systems. For example, the Generalized Uberlingen Model (Brahms-GUM) simulates air transportation practices, focusing on how pilots and air traffic controllers interact with automated systems in safety-critical, time pressured encounters. Spatial cognition is pervasive: scanning displays of multiple workstations; coordinating airspaces and flight paths; and prioritizing and timing interventions to maintain aircraft separations. Brahms-GUM demonstrates how events may become unpredictable when aspects of the work system are missing or malfunctioning, making a routinely complicated system into one that is cognitively complex and becomes out of control. Normally, asynchronous processes become coupled in space and time, leading to difficulty comprehending the situation ("what is happening now") as a familiar multi-modal flow of events. Such examples illustrate the dynamics of spatial cognition inherent in our conceptually situated experience--our consciousness--of who we are and what we are doing. PMID- 26271311 TI - Efficacy and site specificity of hydrogen abstraction from DNA 2-deoxyribose by carbonate radicals. AB - The carbonate radical anion CO(3)(*-) is a potent reactive oxygen species (ROS) produced in vivo through enzymatic one-electron oxidation of bicarbonate or, mostly, via the reaction of CO(2) with peroxynitrite. Due to the vitally essential role of the carbon dioxide/bicarbonate buffer system in regulation of physiological pH, CO(3)(*-) is arguably one of the most important ROS in biological systems. So far, the studies of reactions of CO(3)(*-) with DNA have been focused on the pathways initiated by oxidation of guanines in DNA. In this study, low-molecular products of attack of CO(3)(*-) on the sugar-phosphate backbone in vitro were analyzed by reversed phase HPLC. The selectivity of damage in double-stranded DNA (dsDNA) was found to follow the same pattern C4' > C1' > C5' for both CO(3)(*-) and the hydroxyl radical, though the relative contribution of the C1' damage induced by CO(3)(*-) is substantially higher. In single stranded DNA (ssDNA) oxidation at C1' by CO3(*-) prevails over all other sugar damages. An approximately 2000-fold preference for 8-oxoguanine (8oxoG) formation over sugar damage found in our study identifies CO(3)(*-) primarily as a one electron oxidant with fairly low reactivity toward the sugar-phosphate backbone. PMID- 26271310 TI - Cannabinoids for the Treatment of Agitation and Aggression in Alzheimer's Disease. AB - Alzheimer's disease (AD) is frequently associated with neuropsychiatric symptoms (NPS) such as agitation and aggression, especially in the moderate to severe stages of the illness. The limited efficacy and high-risk profiles of current pharmacotherapies for the management of agitation and aggression in AD have driven the search for safer pharmacological alternatives. Over the past few years, there has been a growing interest in the therapeutic potential of medications that target the endocannabinoid system (ECS). The behavioural effects of ECS medications, as well as their ability to modulate neuroinflammation and oxidative stress, make targeting this system potentially relevant in AD. This article summarizes the literature to date supporting this rationale and evaluates clinical studies investigating cannabinoids for agitation and aggression in AD. Letters, case studies, and controlled trials from four electronic databases were included. While findings from six studies showed significant benefits from synthetic cannabinoids-dronabinol or nabilone-on agitation and aggression, definitive conclusions were limited by small sample sizes, short trial duration, and lack of placebo control in some of these studies. Given the relevance and findings to date, methodologically rigorous prospective clinical trials are recommended to determine the safety and efficacy of cannabinoids for the treatment of agitation and aggression in dementia and AD. PMID- 26271312 TI - Levels of F2-isoprostanes, F4-neuroprostanes, and total nitrate/nitrite in plasma and cerebrospinal fluid of patients with traumatic brain injury. AB - Several events occurring during the secondary damage of traumatic brain injury (TBI) can cause oxidative stress. F(2)-isoprostanes (F(2)-IsoPs) and F(4) neuroprostanes (F(4)-NPs) are specific lipid peroxidation markers generated from arachidonic acid and docosahexaenoic acid, respectively. In this study, we evaluated oxidative stress in patients with moderate and severe TBI. Since sedatives are routinely used to treat TBI patients and propofol has been considered an antioxidant, TBI patients were randomly treated with propofol or midazolam for 72 h postoperation. We postoperatively collected cerebrospinal fluid (CSF) and plasma from 15 TBI patients for 6-10 d and a single specimen of CSF or plasma from 11 controls. Compared with the controls, the TBI patients exhibited elevated levels of F(2)-IsoPs and F(4)-NPs in CSF throughout the postsurgery period regardless of the sedative used. Compared with the group of patients who received midazolam, those who received propofol exhibited markedly augmented levels of plasma F(2)-IsoPs, which were associated with higher F(4)-NPs levels and lower total nitrate/nitrite levels in CSF early in the postsurgery period. Furthermore, the higher CSF F(2)-IsoPs levels correlated with 6-month and 12-month worse outcomes, which were graded according to the Glasgow Outcome Scale. The results demonstrate enhanced oxidative damage in the brain of TBI patients and the association of higher CSF levels of F(2)-IsoPs with a poor outcome. Moreover, propofol treatment might promote lipid peroxidation in the circulation, despite possibly suppressing nitric oxide or peroxynitrite levels in CSF, because of the increased loading of the lipid components from the propofol infusion. PMID- 26271313 TI - Tensiomyography parameters and jumping and sprinting performance in Brazilian elite soccer players. AB - Tensiomyography has been suggested as an indirect marker of muscle stiffness, which is associated with strength/power performance. Therefore, it is reasonable to suggest that tensiomyography parameters could be associated with power-related motor tasks. The purpose of this study was to investigate the association between tensiomyography parameters (from rectus and biceps femoris) and jumping and sprinting abilities in elite soccer players. In addition, we used tensiomyography parameters to compare the lateral symmetry between dominant and non-dominant legs. Twenty elite soccer players (age: 23.3 +/- 4.8 years; height: 183.5 +/- 6.6 cm; weight: 77.8 +/- 7.5 kg) volunteered to participate in the study. Significant moderate negative correlations between biceps femoris displacement and contact time (r = -0.5, p = 0.03), rectus femoris displacement and contact time (r = 0.51, p = 0.02), and a significant moderate correlation between biceps femoris displacement and reactive strength index (r = 0.5, p = 0.03) were found. There were no correlations between tensiomyography parameters and power-related motor tasks. In addition, no differences in tensiomyography parameters between dominant and non-dominant legs were found. Our data suggest that tensiomyography parameters are not associated with power-related motor tasks performance in elite soccer players. PMID- 26271314 TI - Academic Institutions' Critical Guidelines for Health Care Workers Who Deploy to West Africa for the Ebola Response and Future Crises. AB - The unprecedented Ebola Virus Disease (EVD) outbreak in West Africa, with its first cases documented in March 2014, has claimed the lives of thousands of people, and it has devastated the health care infrastructure and workforce in affected countries. Throughout this outbreak, there has been a critical lack of health care workers (HCW), including physicians, nurses, and other essential non clinical staff, who have been needed, in most of the affected countries, to support the medical response to EVD, to attend to the health care needs of the population overall, and to be trained effectively in infection protection and control. This lack of sufficient and qualified HCW is due in large part to three factors: 1) limited HCW staff prior to the outbreak, 2) disproportionate illness and death among HCWs caused by EVD directly, and 3) valid concerns about personal safety among international HCWs who are considering responding to the affected areas. These guidelines are meant to inform institutions who deploy professional HCWs. PMID- 26271316 TI - [Cardiopulmonary bypass duration as predictor of immediate results after cardiac surgery]. AB - It was analyzed the results of treatment of 152 patients who underwent heart valve surgery. Depending on cardiopulmonary bypass (CPB) duration patients were divided into 4 groups: the 1st--up to 90 min, the 2nd--90-120 min, the 3rd--120 180 min, the 4th--more than 180 min. Severity of initial comorbidities was comparable in all groups. It was revealed that CPB duration effects on intraoperative blood loss, incidence of acute renal failure, encephalopathy, use of inotropic and angiotonic support (p<0.05). Accession of CPB duration was associated with increased number of postoperative complications in all groups (p<0.05). "Critical periods" of CPB for every type of postoperative complications are defined. PMID- 26271317 TI - [Perforating veins insufficiency in patients with varicose disease]. AB - MATERIAL AND METHODS: It was analyzed the results of complex survey and treatment of 181 patients with varicose disease CEAP degrees C3-C6. Ultrasonic scanning was applied to define localization, severity and extension of blood reflux in venous system. RESULTS: Superficial reflux was revealed in all patients, perforating--in 59.7%, deep--in 22.8% of cases. We concluded that high-intensive total-subtotal blood reflux in superficial veins was main hemodynamic factor resulted perforating insufficiency in 42% of patients, high-intensive deep reflux--in 17.7% of cases additionally. In patients with subcompensated course of disease superficial reflux removal and large perforating veins (diameter 4.5+/-0.5 mm) ligation are advisable. Small perforating veins insufficiency (diameter 3.5+/-0.5 mm) is eliminated independently after superficial reflux removal. Two-staged treatment should be used in patients with decompensated course of disease and trophic disorders ofshin. Perforating veins sclerotherapy under ultrasonic control is advisable secondarily after superficial reflux removal. PMID- 26271318 TI - [Cold-plasma sternotomy and postoperative sternal consolidation]. AB - MATERIAL AND METHODS: It is presented the results of cold-plasma sternotome application in 16 patients. Efficiency of this technique, its effect on sternal reparation as well as on the incidence of early and remote (4-5 months) postoperative wound complications were analyzed. Control group included 19 patients who underwent conventional sternotomy using high-temperature electrocoagulation and medical wax for hemostasis. Risk factors for sternal infection were comparable in both groups. Physical examination and computed tomography were performed in all patients to access incidence of complications and degree of bone tissueconsolidation respectively in postoperative period. RESULTS: It is shown that cold-plasma sternotomy leads to early inflammation resolution in oversplitting area and to reduction of wound complications incidence. PMID- 26271319 TI - [Robot-assisted operations for non-organ retroperitoneal tumors]. AB - MATERIAL AND METHODS: Robot-assisted operations for non-organ retroperitoneal tumors were performed in 20 patients. The biggest tumor's diameter was 160 mm, the smallest--32 mm, mean value was 79.1+/-37.8 mm. According to morphological investigation data lymphangioma was diagnosed in 4 (20%) patients, lipoma--in 3 (15%) cases, peritoneal cyst--in 2 (10%) patients. Solitary lymphatic node, teratoma, leiomyosarcoma, accessory stomach, bronchogenic cyst, adenogenous cancer, ureterocele, megaureter, schwannoma, leiomyoma, malignant paraganglioma were observed in 1 (5%) case respectively. RESULTS: Surgery duration was 138+/ 55.9 min. Blood loss was 69+/-112.7 ml (range 0-500 ml). Intraoperative complications (bleeding) were diagnosed in 3 (15%) patients. There were no conversions. Robot-assisted variant has been demonstrated in case of non-organ retroperitoneal tumors with diameter not more than 100-120 mm. PMID- 26271320 TI - [Blood iron metabolism in patients with stomach cancer]. AB - AIM: To investigate the changes of iron metabolism values in patients with stomach cancer degree II and III within 7 days after surgery. MATERIAL AND METHODS: Levels of ferritin, transferrin, serum iron and unsaturated iron binding capacity were defined in 24 patients with stomach cancer preoperatively and in 1, 3 and 7 days after surgery using biochemical analyzer Cobas Integra 400. Comparison group included donors without cancer. RESULTS: Studied parameters were normal before surgery excluding serum iron and hemoglobin. Level of ferritin significantly increased by 160% and transferrin decreased by 78% in comparison with those in donors in 7 days postoperatively (p<0.05; Mann-Whitney criterion). Total iron binding capacity considerably reduced by 300%. There are significant changes of serum iron values from the 1st to the 7th days postoperatively. It is suggested the supposition about detoxication role of increased level of ferritin as one of the mechanisms explaining efficiency of intraoperative autoplasmachemotherapy. PMID- 26271321 TI - [Laparoscopic operations for chronic duodenal obstruction in children]. AB - Brief literature review devoted to chronic duodenal obstruction is presented in the article. We described an experience of treatment of 5 children with mechanical form of chronic duodenal obstruction. Duodenal stenosis was observed in 2 patients. Arteriomesenteric compression caused chronic duodenal obstruction in other children. Duodenal obstruction was cured using laparoscopy in all cases. Thus enteroalimentation has been started in early terms and intensive care unit stay and hospital stay was reduced. PMID- 26271322 TI - [Spleen trauma in children]. AB - The aim was to determine blood loss degree in case of spleen trauma in children and to justify safety of victims treatment without surgery. MATERIALS AND METHODS: It was performed retrospective cohort study of 105 autopsies of children who died of combined trauma. 33 of them had spleen injury. Prospective cohort study was performed in 75 children with spleen injury, 69 (92%) from whom were treated without surgery. RESULTS: It was established that thanatogenetic feature of spleen injury in children is moderate blood loss (89.6% of victims), incidence of large and massive blood loss was 6.8% and 3.4% respectively. In unoperated children blood loss did not exceed 15% of blood volume. In group of operated children (n=6; 8%) incidence of large blood loss was 4% (n=3) and did not exceed 28% of blood volume. Prevalence of moderate blood loss in case of spleen trauma due to anatomic and physiological features and mechanisms of spleen injury is theoretically justified. PMID- 26271323 TI - [Interintestinal anastomoses formation using permanent magnet in surgical treatment of children with intestinal stomas]. AB - It was analyzed the results of treatment of 48 children aged from 1 month to 14 years. In these observations by the 6th - 7th days after doubleintestinalstoma formation magnetic dies with inductance from 300 to 360 mTl and energy force at least 255 kJ/m3 were introduced into lumen of afferent and efferent intestinal loops. Attractive or compression force between dies was 600 g, i.e. force per 1 cm2 was 200 g according to dies' surface 1.12.83.0 cm. Magnets are not only surgical instruments but also physiotherapeutic devices improving microcirculation and stimulating regeneration in the area of anastomosis. Interintestinal anastomosis has been completely formed for 5-7 days. Thereafter magnetic dies have been removed. Stool was normalized in 45 of 48 observations after surgery (1-3 times daily). Intestinal discharge from ileostomy reduced to minimal amount. In 2 patients irregular bowel movements was observed due to adhesive stenosis of interintestinal anastomosis. Magnetic dies can't be established in 1 case due to adhesive process. Hospital stay was from 10 to 25 days in 41 children. 7 patients were discharged for outpatient treatment later. All children were under observation for the period 2-4 months after discharge. Signs of hypotrophy including body weight deficit within 10% of age norm were diagnosed only in 3 children with prematurity degree I-II. Hereafter children were repeatedly hospitalized; intestinal stomas were surgically removed using conventional technique. Thus complete convalescence was obtained. PMID- 26271324 TI - [Modified Limberg plasty in treatment of epithelial coccygeal passage]. AB - The aim was analysis of results of Limberg skin-plastic closure of wound defect after excision of extensive fistulous forms of coccygeal passage with some modifications. MATERIALS AND METHODS: 41 patients with fistulous form of epithelial coccygeal passage degree III were enrolled into investigation. Mean age was 35.6+/-6.4 years. The modification consisted of asymmetric displacement of the lowermost part of excised diamond-shaped defect laterally from the median line and fixation of flap to inter-gluteal fold bottom especially its caudal part. RESULTS: Noncomplicated course of early postoperative period with wound healing by first intention was observed in 38 (92.7%) patients. Recurrent coccygeal passage developed in 1 (2.4%) patient and it was limited (fistulous passage in one of the wound edges). PMID- 26271325 TI - [The state of cytokine status in patients with mechanical jaundice of benign origin]. AB - The results of survey of 67 patients with obstructive jaundice (OJ) of benign origin are analyzedin the article. In all patients the cause of obstructive jaundice was choledocholithiasis. The degree of hepatic dysfunction (HD) was identified taking into account of cholestasis (total serum bilirubin and alkaline phosphatase activity in blood) and cytolysis syndromes (levels of alanine aminotransferase and aspartate aminotransferase). Liver dysfunction degree I was observed in 21 patients, degree II--in 14, degree III--in 10 and degree IV--in 9 patients. In 13 patients OJ was complicated with purulent cholangitis (PCh). Serum concentration of TNF-alpha, IFN-gamma, IL-2, IL-4, IL-6, IL-10 was determined. Cytokine status imbalance was diagnosed in all patients with benign mechanical jaundice on admission. Levels of serum proinflammatory cytokines TNF alpha, IFN-gamma and IL-6 were greater and the level of IL-2 was lower than those in healthy people. The analysis has showed that severity of cytokine imbalance depends on the degree of LD and level of hyperbilirubinemia. Imbalance in cytokine regulation manifests in disorders of pro- and anti-inflammatory cytokinesratio. PMID- 26271326 TI - [The first experience of using a single-layer intra-abdominal collagen plate]. AB - The aim of this study was to define the possibility of using a collagen substance CollGARA as a protective barrier between the polypropylene mesh implant and abdominal organs. The drug is a sterile bioabsorbable membrane consisting of refolded equine collagen. Indications--use as barrier separating adjoining tissues and organs in the areas of the abdominal cavity, where the formation of adhesions. MATERIALS AND METHODS: Were performed 10 operations in patients with ventral hernias with different localization. 8 patients had postoperative hernia in 2--linea alba hernia. 8 patients were operated open, 2--laparoscopically. After intra-abdominal hernia repair was performed plastic mesh implant, delimiting it from the abdominal cavity membrane CollGARA. Serious complications from the abdominal cavity and the surgical wound wasnt observed. RESULTS: The first experience with intra-abdominal plastic polypropylene mesh implant coated with collagen plate indicates the possibility of applying this method in the future. PMID- 26271328 TI - Correction. PMID- 26271327 TI - Design of a randomized controlled trial of disclosing genomic risk of coronary heart disease: the Myocardial Infarction Genes (MI-GENES) study. AB - BACKGROUND: Whether disclosure of a genetic risk score (GRS) for a common disease influences relevant clinical outcomes is unknown. We describe design of the Myocardial Infarction Genes (MI-GENES) Study, a randomized clinical trial to assess whether disclosing a GRS for coronary heart disease (CHD) leads to lowering of low-density lipoprotein cholesterol (LDL-C) levels. METHODS AND DESIGN: We performed an initial screening genotyping of 28 CHD susceptibility single-nucleotide polymorphisms (SNPs) that are not associated with blood pressure or lipid levels, in 1000 individuals from Olmsted County, Minnesota who were participants in the Mayo Clinic BioBank and met eligibility criteria. We calculated GRS based on 28 SNPs and will enroll 110 patients each in two CHD genomic risk categories: high (GRS >=1.1), and average/low (GRS <1.1). The study coordinator will obtain informed consent for the study that includes placing genetic testing results in the electronic health record. Participants will undergo a blood draw and return 6-10 weeks later (Visit 2) once genotyping is completed and a GRS calculated. At this visit, patients will be randomized (1:1) to receive CHD risk estimates from a genetic counselor based on a conventional risk score (CRS) vs. GRS, followed by shared decision making with a physician regarding statin use. Three and six months following the disclosure of CHD risk, participants will return for measurement of fasting lipid levels and assessment of changes in dietary fat intake and physical activity levels. Psychosocial measures will be assessed at baseline and after disclosure of CHD risk. DISCUSSION: The proposed trial will provide insights into the clinical utility of genetic testing for CHD risk assessment. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT01936675 . PMID- 26271330 TI - Implant treatment in periodontally compromised subjects--quality of life and patient satisfaction. AB - OBJECTIVES: The aims of this study were to determine the quality of life of periodontally compromised patients after implant treatment (primary aim) and their satisfaction with the restoration and treatment approach (secondary aim). MATERIAL AND METHODS: In this study, 61 adult subjects were evaluated following non-surgical periodontal treatment, under regular maintenance and implant therapy with a fixed restoration. Oral health-related quality of life (OHQoL) was assessed using the German short form of the Oral Health Impact Profile (OHIP G14). Patient satisfaction with the restoration and treatment procedure was investigated applying a self-designed questionnaire focusing on social psychological aspects. Statistical analysis of the collected data was performed using Kruskal-Wallis and Man-Whitney U test for the relationship between OHIP score and number of implants, patient age and level of education. RESULTS: The average OHIP-G14 score of the examined study population was 2.78 (SD +/-4.2), while the item pain had the biggest influence on the number of points. No statistical significance was detected between the relationship of OHIP-G14 score and the number of placed implants (p = 0.98). Furthermore, there was no statistically significant correlation between OHIP-G14 score and patient age (p = 0.67) or for level of education (p = 0.39). The questionnaire focusing on patient satisfaction showed a high level of contentment in this study population. All patients declared that they would repeat the treatment and most (98.4%) would recommend it to their friends. Furthermore, a high level of satisfaction with aesthetics, stability, cleanability and speech comprehension was reported. CONCLUSION: The examined study population showed a quality of life after implant therapy comparable to pre-existing reference values of a healthy non-restored population. There was no statistical significance between OHIP-G 14 score and the number of implants, patients' age and education level. Analysis of the satisfaction with the realized implant therapy provided consistently positive results. CLINICAL RELEVANCE: When restoring periodontally compromised patients, implant treatment should be considered to achieve potentially higher oral health related quality of life compared to for example removable dentures. This needs to be investigated in randomized controlled clinical trials. PMID- 26271329 TI - Relationship of BMI to the incidence of hypertension: a 4 years' cohort study among children in Guangzhou, 2007-2011. AB - BACKGROUND: In China, there has been a dramatic increase in overweight and obesity among children and adolescents in recent decades. However, little longitudinal studies reported BMI in relation to the risk for hypertension among children in China. We examined the longitudinal relations between BMI and hypertension in Chinese schoolchildren via a retrospective cohort study. METHODS: The cohort study was carried out in 7203 children (3821 boys and 3382 girls) in Guangzhou aged 6-8 years, with a continuous 4 years of follow-up. The participants, evaluated by body mass index (BMI), were categorized as thinness, normal weight, overweight, and obesity groups. The age and gender-specific BMI cutoffs newly developed by the Working Group on Obesity in China (WGOC) were used to define overweight and obesity. The thinness was defined by the international age- and gender-specific cut-off points for BMI for thinness grade 1. Hypertension was defined by using percentiles of systolic and diastolic values on the basis of height percentile, age, and gender. The Cox proportional hazards model was used to estimate the single or joint effect of BMI on the risk of hypertension. This study was approved by The Ethical Committee of School of Public Health, Sun Yat-sen University. RESULTS: During a follow-up of 4 years, a shocking high cumulative incidence of hypertension was found in Chinese overweight (50.1 %) and obesity (70 %) schoolchildren. The incidence of children hypertension were markedly higher among overweight and obesity group than normal weight and thinness group (24.3 %, 18.5 % vs 11.1 %, 7.4 %). Compared with the children in the normal weight group, the adjusted HRs and 95 % CIs of developing hypertension in thinness, overweight, and obesity group were 0.972 (0.851, 1.110), 1.313 (1.179, 1.461), and 1.816 (1.634, 2.081), respectively. Additionally, the protective effect of thinness on hypertension was observed in boys 0.808 (0.666, 0.981), but not in girls 1.158 (0.966, 1.389). CONCLUSIONS: The 4-year longitudinal study indicated that the overweight and obesity can predict the higher risk of hypertension in Chinese children, whereas, the thinness predict the lower risk of hypertension only in boys. PMID- 26271331 TI - Learning before leaping: integration of an adaptive study design process prior to initiation of BetterBirth, a large-scale randomized controlled trial in Uttar Pradesh, India. AB - BACKGROUND: Pragmatic and adaptive trial designs are increasingly used in quality improvement (QI) interventions to provide the strongest evidence for effective implementation and impact prior to broader scale-up. We previously showed that an on-site coaching intervention focused on the World Health Organization Safe Childbirth Checklist (SCC) improved performance of essential birth practices (EBPs) in one facility in Karnataka, India. We report on the process and outcomes of adapting the intervention prior to larger-scale implementation in a randomized controlled trial in Uttar Pradesh (UP), India. METHODS: Initially, we trained a local team of physicians and nurses to coach birth attendants in SCC use at two public facilities for 4-6 weeks. Trained observers evaluated adherence to EBPs before and after coaching. Using mixed methods and a systematic adaptation process, we modified and strengthened the intervention. The modified intervention was implemented in three additional facilities. Pre/post-change in EBP prevalence aggregated across facilities was analyzed. RESULTS: In the first two facilities, limited improvement was seen in EBPs with the exception of post-partum oxytocin. Checklists were used <25 % of observations. We identified challenges in physicians coaching nurses, need to engage district and facility leadership to address system gaps, and inadequate strategy for motivating SCC uptake. Revisions included change to peer-to-peer coaching (nurse to nurse, physician to physician); strengthened coach training on behavior and system change; adapted strategy for effective leadership engagement; and an explicit motivation strategy to enhance professional pride and effectiveness. These modifications resulted in improvement in multiple EBPs from baseline including taking maternal blood pressure (0 to 16 %), post-partum oxytocin (36 to 97 %), early breastfeeding initiation (3 to 64 %), as well as checklist use (range 32 to 88 %), all p < 0.01. Further adaptations were implemented to increase the effectiveness prior to full trial launch. CONCLUSIONS: The adaptive study design of implementation, evaluation, and feedback drove iterative redesign and successfully developed a SCC-focused coaching intervention that improved EBPs in UP facilities. This work was critical to develop a replicable BetterBirth package tailored to the local context. The multi-center pragmatic trial is underway measuring impact of the BetterBirth program on EBP and maternal-neonatal morbidity and mortality. TRIAL REGISTRATION: CLINICAL TRIALS IDENTIFIER: NCT02148952 . PMID- 26271332 TI - Human cystic and alveolar echinococcosis in the Tibet Autonomous Region (TAR), China. AB - Human cystic echinococcosis (CE) is known to be endemic in the Tibet Autonomous Region (TAR), China; however, there is relatively little data from hospital records or community prevalence studies, and the situation regarding occurrence of human alveolar echinococcosis (AE) is unclear. Here we review the available reports about human echinococcosis in the seven prefectures of TAR. In addition, two pilot studies by mass screening using ultrasound (with serology) were undertaken (2006/7) in Dangxiong County of Lhasa Prefecture (north central TAR) and Dingqing County of Changdu Prefecture (eastern TAR). In Dangxiong County a prevalence of 9.9% (55/557) for human CE was obtained but no human AE cases were detected. By contrast, in Dingqing County (N= 232 persons screened), 11 CE cases (4.7%) and 12 AE cases (5.2%) (including one mixed CE and AE case) were diagnosed by ultrasound. Hospital records and published reports indicated that CE cases were recorded in all of seven prefectures in Tibet Autonomous Region, and AE cases in four prefectures. Incidence rates of human CE were estimated to range from 1.9 to 155 per 100,000 across the seven prefectures of TAR, with a regional incidence of 45.1 per 100,000. Incidence of AE was estimated to be between 0.6 and 2.8 cases per 100,000. Overall for TAR, human AE prevalence appeared relatively low; however, the pilot mass screening in Dingqing in eastern TAR indicated that human AE disease is a potential public health problem, possibly similar to that already well described in Tibetan communities bordering TAR in north-west Sichuan and south-west Qinghai provinces. PMID- 26271334 TI - Extracellular fluid flow and chloride content modulate H(+) transport by osteoclasts. AB - BACKGROUND: Bone resorption takes place within the basic multicellular units (BMU), and the surface to be resorbed is isolated from adjacent bone surfaces by a sealing zone between osteoclast membrane and bone matrix, which defines the limits of the resorption lacuna. Considering that the extracellular fluid (ECF) in both BMU and the resorption lacuna can be isolated from its surroundings, I hypothesize that flow and ion composition of the bone ECF in these sites might contribute to the regulation of osteoclast H(+) secretion. To investigate this hypothesis, I evaluated the H(+) secretion properties of individual osteoclasts and osteoclast-like cells (OCL-cells) and investigated whether changes in flow or chloride content of the extracellular solution modify the H(+) secretion properties in vitro. RESULTS: The results show that 1) osteoclasts are unable to secrete H(+) and regulate intracellular pH (pHi) under continuous flow conditions and exhibit progressive intracellular acidification; 2) the cessation of flow coincides with the onset of H(+) secretion and subsequent progressive intracellular alkalinization of osteoclasts and OCL-cells; 3) osteoclasts exhibit spontaneous rhythmic oscillations of pHi in non-flowing ECF, 4) pHi oscillations are not abolished by concanamycin, NPPB, or removal of extracellular Na(+) or Cl( ); 5) extracellular Cl(-) removal modifies the pattern of oscillations, by diminishing H(+) secretion; 6) pHi oscillations are abolished by continuous flowing of ECF over osteoclasts and OCL-cells. CONCLUSIONS: The data suggest, for the first time, that ECF flow and Cl(-) content have direct effects on osteoclast H(+) secretion and could be part of a mechanism determining the onset of osteoclast H(+) secretion required for bone resorption. PMID- 26271336 TI - Total Synthesis of the Potent HIF-1 Inhibitory Antitumor Natural Product, (8R) Mycothiazole, via Baldwin-Lee CsF/CuI sp(3)-sp(2)-Stille Cross-Coupling. Confirmation of the Crews Reassignment. AB - A convenient asymmetric total synthesis of the potent HIF-1 inhibitory antitumor natural product, (-)- or (+)-(8R)-mycothiazole (1), is described. Not only does our synthesis confirm the 2006 structural reassignment made by Crews ( Crews , P. , et al. J. Nat. Prod. 2006 , 69 , 145 ), it revises the [alpha]D data previously reported for this molecule in MeOH from -13.7 degrees to +42.3 degrees . The newly developed route to (8R)-1 sets the C(8)-OH stereocenter via Sharpless AE/2,3-epoxy alcohol reductive ring opening and utilizes two Baldwin-Lee CsF/cat. CuI Stille cross-coupling reactions with vinylstannanes 8 and 3 to efficiently elaborate the C(1)-C(4) and C(14)-C(18) sectors. PMID- 26271335 TI - Ribozyme-Spherical Nucleic Acids. AB - Ribozymes are highly structured RNA sequences that can be tailored to recognize and cleave specific stretches of mRNA. Their current therapeutic efficacy remains low due to their large size and structural instability compared to shorter therapeutically relevant RNA such as small interfering RNA (siRNA) and microRNA (miRNA). Herein, a synthetic strategy that makes use of the spherical nucleic acid (SNA) architecture to stabilize ribozymes and transfect them into live cells is reported. The properties of this novel ribozyme-SNA are characterized in the context of the targeted knockdown of O(6)-methylguanine-DNA methyltransferase (MGMT), a DNA repair protein involved in chemotherapeutic resistance of solid tumors, foremost glioblastoma multiforme (GBM). Data showing the direct cleavage of full-length MGMT mRNA, knockdown of MGMT protein, and increased sensitization of GBM cells to therapy-mediated apoptosis, independent of transfection agents, provide compelling evidence for the promising properties of this new chemical architecture. PMID- 26271337 TI - Waste lubricating oil removal in a batch reactor by mixed bacterial consortium: a kinetic study. AB - The growth kinetics and biodegradation of two waste lubricating oil samples including waste engine oil (WEO) and waste transformer oil (WTO) were studied using pure isolates and mixed culture of Ochrobactrum sp. C1 and Bacillus sp. K1. The mixed culture significantly influenced degradation efficiency of the pure isolates through bioaugmentation process. In particular, the mixed culture was capable of growing on various n-alkanes and polycyclic aromatic hydrocarbons and was able to tolerate unusually high concentrations of waste lubricants (WEO-86.0 g/L and WTO-81.5 g/L). The initial concentration of waste lubricating oils has been varied in the range of 1-10 % (v/v). Under this experimental range, the bacterial growth has been observed to follow Haldane-type kinetics characterizing the presence of substrate inhibition. Haldane model was used to fit the exponential growth data and the following kinetic parameters were obtained: MU max = 0.078 h(-1), K S = 23.101 g/L, K i = 43.844 g/L for WEO; and MU max = 0.044 h(-1), K S = 10.662 g/L, K i = 58.310 g/L for WTO. The values of intrinsic kinetic parameters, like specific growth rate MU max, half saturation constant, K S, inhibition constant, K i and the maximum substrate concentration, S max and growth yield coefficient Y x/s , have been determined using each model hydrocarbon and their mixture as limiting substrate. Relative changes in the values of the kinetic parameters have been correlated to the number of carbon atoms present in n-alkanes. The metabolites from degradation of model hydrocarbon compounds have been identified by GC-MS to elucidate the possible pathway of waste lubricating oil degradation process. PMID- 26271339 TI - Synergistic assembly of nanoparticles in smectic liquid crystals. AB - We report synergistic co-assembly between smectic A liquid crystal (SmA LC) and planar anchoring fluorosilane functionalized silica (F-SiO2) nanoparticles (NPs). Both scanning electron microscope (SEM) images and grazing incidence X-ray diffraction (GIXD) patterns show that when cooled from the isotropic phase to SmA phase, F-SiO2 NPs (100-500 nm in diameter) migrate from the bottom to the top of the LC film through the central cusp defects of toric focal conic domains (TFCDs). When the NPs form a monolayer on top, replacing the LC/air interface, vertically aligned SmA layers are formed between the top and bottom planar surfaces. When F-SiO2 NP diameter is small (<500 nm), we observe a weak-anchoring regime, where NPs do not cause appreciable layer curvature and NP migration is driven by surface energy. When F-SiO2 particle diameter > 500 nm, strong distortions occur in the smectic layers, and the particle is found suspended at the TFCD defect core. The knowledge of the intermediate states of the NP/LC hybrid structures will provide valuable insights to assemble functional nanomaterials such as quantum dots and metallic NPs in an anisotropic medium, and take advantage of their collective assembly behaviors to create more complex and dynamic structures. PMID- 26271340 TI - Enhanced conductivity of (110)-textured ScSZ films tuned by an amorphous alumina interlayer. AB - Herein a novel strategy to tune the crystallite orientation and the ionic conductivity of solid electrolyte films through interfacial control has been reported. 10 mol% Sc2O3-doped ZrO2 (10ScSZ) thin films were prepared with an amorphous alumina (AO) interlayer (AO/10ScSZ) using magnetron sputtering. It has been found that a (110)-preferred orientation develops in AO/10ScSZ films annealed at 1000 degrees C due to a strong interfacial interaction, while 10ScSZ films deposited without the AO interlayer are (111)-textured. The (110)-oriented AO/10ScSZ films show an ionic conductivity nearly 4 times higher than that of the (111)-oriented 10ScSZ films. This is explained by the fact that the (110)-texture provides faster migration pathways with lower energy barrier for oxygen vacancies. These results reveal the relationship between the crystal structure and the conductivity of AO/ScSZ heterostructured films, which can facilitate the development of high-performance multilayered electrolytes and enable the miniaturization of solid-state electrochemical devices operable at temperatures below 600 degrees C. PMID- 26271338 TI - New Synthesis Route of Hydrogel through A Bioinspired Supramolecular Approach: Gelation, Binding Interaction, and in Vitro Dressing. AB - Peptide-based supramolecular hydrogels have been comprehensively investigated in biomaterial applications because of their unique bioactivity, biofunctionality, and biocompatible features. However, the presence of organic building blocks in peptide-based hydrogels often results in low mechanical stability. To expand their practical use and range of applications, it is necessary to develop the tool kit available to prepare bioinspired, peptide-based supramolecular hydrogels with improved mechanical stability. In this paper, we present an innovative electrostatic and cross-linking approach in which naphthyl-Phe-Phe-Cys (NapFFC) oligopeptides are combined with gold nanoparticles (AuNPs) and calcium ions (Ca(2+)) to produce peptide-based supramolecular hydrogels. We further investigate the interactions among NapFFC, AuNPs and Ca(2+) by microscopy. The morphology of the nanofibrous network constructions and the binding forces exhibited from the hydrogel demonstrated that the combination of two mechanisms successfully enhanced the mechanical stability through the formation of a densely entangled fibrous network of peptide multimers that is attributed to the AuNP linkage and Ca(2+)-induced agglomeration. UV-vis spectrophotometry and fluorescence analysis were also used to demonstrate the enhanced stability of the hydrogel under various conditions such as thermal, solvent erosion, pH value and sonication. All results indicate that the presence of AuNPs and Ca(2+) can strengthen the prepared hydrogel by more than doubling the diameter of NapFFC nanofibers, enabling the formation of stronger frameworks and slowing the release of components. Further experiments confirmed that HeLa cells can grow on the bioinspired NapFFC-AuNP hydrogel and exhibit high cell viability and that these cells were killed on contact with a hydrogel containing a drug. Our peptide-based supramolecular hydrogels prepared from the observed electrostatic and cross linking mechanisn exhibited a significantly improved mechanical stability, making them well suited to use as a drug carrier in hydrogel dressings and as extracellular materials (ECMs) for tissue engineering. PMID- 26271333 TI - Vitamin D deficiency in chronic inflammatory rheumatic diseases: results of the cardiovascular in rheumatology [CARMA] study. AB - INTRODUCTION: The aim was to study the association between 25-hydroxyvitamin D (25(OH)D) levels and the clinical characteristics of patients with chronic inflammatory rheumatic diseases (CIRD). METHODS: We studied a cross-section from the baseline visit of the CARMA project (CARdiovascular in rheuMAtology), a 10 year prospective study evaluating the risk of cardiovascular events in rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) patients, and non-CIRD patients who attended rheumatology outpatient clinics from 67 hospitals in Spain. Non-CIRD group was frequency matched by age with the joint distribution of the three CIRD groups included in the study. 25(OH)D deficiency was defined if 25(OH)D vitamin levels were < 20 ng/ml. RESULTS: 2.234 patients (775 RA, 738 AS and 721 PsA) and 677 non-CIRD subjects were assessed. The median (p25-p75) 25(OH)D levels were: 20.4 (14.4-29.2) ng/ml in RA, 20.9 (13.1-29.0) in AS, 20.0 (14.0-28.8) in PsA, and 24.8 (18.4-32.6) ng/ml in non-CIRD patients. We detected 25(OH)D deficiency in 40.5 % RA, 39.7 % AS, 40.9 % PsA and 26.7 % non CIRD controls (p < 0.001). A statistically significant positive association between RA and 25(OH)D deficiency was found (adjusted (adj.) OR = 1.46; 95 % CI = 1.09-1.96); p = 0.012. This positive association did not reach statistical significance for AS (adj. OR 1.23; 95 % CI = 0.85-1.80) and PsA (adj. OR 1.32; 95 % CI = 0.94-1.84). When the parameters of disease activity, severity or functional impairment were assessed, a marginally significant association between 25(OH)D deficiency and ACPA positivity in RA patients (adj. OR = 1.45; 95 % CI = 0.99-2.12; p = 0.056), and between 25(OH)D deficiency and BASFI in AS patients (adj. OR = 1.08; 95 % CI = 0.99-1.17); p = 0.07) was also found. CONCLUSIONS: Patients with RA show an increased risk of having 25(OH)D deficiency compared to non-CIRD controls. PMID- 26271341 TI - Feasibility of Targeting PIK3CA Mutations in Head and Neck Squamous Cell Carcinoma. AB - PIK3CA is the only frequently-mutated, directly druggable oncogene in head and neck squamous cell carcinoma (HNSCC). However, it is unclear if a molecularly driven intervention trial can be launched successfully, particularly within a single-institution setting secondary to the infrastructure necessary for mutation detection, mutation prevalence, and patient willingness to participate. This study aimed to evaluate 1) local frequency of PIK3CA activating mutations in HNSCC, 2) timeliness of our mutation-profiling clinical pathway, and 3) patients' willingness to enroll in a novel neoadjuvant drug trial. Tissue biopsies of 25 consecutive cases of HNSCC were tested for activating PIK3CA mutations at three mutational hotspots by real-time polymerase chain reaction. Mutations prevalence and number of working days accrued in determining PIK3CA mutational status were calculated. In addition, 30 HNSCC patients were surveyed prospectively regarding their willingness to participate in a hypothetical drug trial. Survey data were summarized descriptively. 4 of 25 (16 %) tumors harbored a PIK3CA activating mutation, including one at codon E542K, two at codon E545K/D, and one at codon H1047R. On average, this result was obtained in approximately 15 working days (range, 9-24 working days). The majority of patients surveyed (70 %) indicated their willingness to participate in a targeted PIK3CA trial. This study provides evidence that within a single institution, PIK3CA activating mutations can be detected with expected frequency, with sufficient timeliness and sufficient patient interest to mount a targeted intervention trial that may lead to improved tumor response in selected HNSCC patients. PMID- 26271342 TI - Haploinsufficiency of interferon regulatory factor 4 strongly protects against autoimmune diabetes in NOD mice. AB - AIMS/HYPOTHESIS: Interferon regulatory factor (IRF)4 plays a critical role in lymphoid development and the regulation of immune responses. Genetic deletion of IRF4 has been shown to suppress autoimmune disease in several mouse models, but its role in autoimmune diabetes in NOD mice remains unknown. METHODS: To address the role of IRF4 in the pathogenesis of autoimmune diabetes in NOD mice, we generated IRF4-knockout NOD mice and investigated the impact of the genetic deletion of IRF4 on diabetes, insulitis and insulin autoantibody; the effector function of T cells in vivo and in vitro; and the proportion of dendritic cell subsets. RESULTS: Heterozygous IRF4-deficient NOD mice maintained the number and phenotype of T cells at levels similar to NOD mice. However, diabetes and autoantibody production were completely suppressed in both heterozygous and homozygous IRF4-deficient NOD mice. The level of insulitis was strongly suppressed in both heterozygous and homozygous IRF4-deficient mice, with minimal insulitis observed in heterozygous mice. An adoptive transfer study revealed that IRF4 deficiency conferred disease resistance in a gene-dose-dependent manner in recipient NOD/severe combined immunodeficiency mice. Furthermore, the proportion of migratory dendritic cells in lymph nodes was reduced in heterozygous and homozygous IRF4-deficient NOD mice in an IRF4 dose-dependent manner. These results suggest that the levels of IRF4 in T cells and dendritic cells are important for the pathogenesis of diabetes in NOD mice. CONCLUSIONS/INTERPRETATION: Haploinsufficiency of IRF4 halted disease development in NOD mice. Our findings suggest that an IRF4-targeted strategy might be useful for modulating autoimmunity in type 1 diabetes. PMID- 26271343 TI - Tissue factor/factor VIIa signalling promotes cytokine-induced beta cell death and impairs glucose-stimulated insulin secretion from human pancreatic islets. AB - AIMS/HYPOTHESIS: Patients diagnosed with type 1 or type 2 diabetes have elevated levels of coagulation factor VIIa (FVIIa) and its receptor tissue factor (TF) in their bloodstream. This may affect the fate of the beta cells. We aimed to study the effects of TF/FVIIa signalling on cytokine-induced beta cell death and islet function in vitro. METHODS: Human pancreatic islets and MIN-6 beta cells were used to study TF mRNA and protein expression using real-time PCR, immunoblotting and flow cytometry. The effects of TF/FVIIa on cytokine-induced beta cell death were studied in MIN-6 cells and human pancreatic islets using cell-death ELISA and propidium iodide and cleaved caspase-3 staining. Effects of TF/FVIIa on the phosphorylation of p38, extracellular signal-regulated kinase and c-Jun N terminal kinase (JNK) were investigated by immunoblotting. Glucose-stimulated insulin secretion (GSIS) from human islets was measured with an insulin ELISA. RESULTS: A combination of the cytokines IL-1beta, TNF-alpha and IFN-gamma induced TF expression in human pancreatic islets and in beta cells. TF/FVIIa did not affect basal beta cell death but, independently of downstream coagulation activity, augmented beta cell death in response to cytokines. The effect of TF/FVIIa on cytokine-induced beta cell death was found to be dependent on the stress kinase JNK, since FVIIa addition potentiated cytokine-induced JNK activation and JNK inhibition abolished the effect of TF/FVIIa on cytokine induced beta cell death. Moreover, TF/FVIIa signalling resulted in inhibition of GSIS from human pancreatic islets. CONCLUSIONS/INTERPRETATION: These results indicate that TF/FVIIa signalling has a negative effect on beta cell function and promotes beta cell death in response to cytokines. PMID- 26271344 TI - Endogenous glucose production increases in response to metformin treatment in the glycogen-depleted state in humans: a randomised trial. AB - AIMS/HYPOTHESIS: Metformin is believed to reduce glucose levels primarily by inhibiting hepatic glucose production. Recent data indicate that metformin antagonises glucagon-dependent glucose output, suggesting that compensatory mechanisms protect against hypoglycaemia. Here, we examined the effect of metformin on glucose metabolism in humans after a glycogen-depleting fast and the role of reduced-function alleles in OCT1 (also known as SLC22A1). METHODS: In a randomised, crossover trial, healthy individuals with or without reduced-function alleles in OCT1 were fasted for 42 h twice, either with or without prior treatment with 1 g metformin twice daily. Participants were recruited from the Pharmacogenomics Biobank of the University of Southern Denmark. Treatment allocation was generated by the Good Clinical Practice Unit, Odense University Hospital, Denmark. Variables of whole-body glucose metabolism were assessed using [3-(3)H]glucose, indirect calorimetry and measurement of substrates and counter regulatory hormones. The primary outcome was endogenous glucose production (EGP). RESULTS: Thirty-seven individuals were randomised. Thirty-four completed the study (12 had none, 13 had one and nine had two reduced-function alleles in OCT1). Three were excluded from the analysis because of early dropout. Metformin significantly stimulated glucose disposal rates and non-oxidative glucose metabolism with no effect on glucose oxidation. This increase in glucose utilisation was explained by a concomitant increase in glycolytic flux and accompanied by increased EGP, most likely mediated by increased plasma lactate, glucagon and cortisol levels. There was no effect of reduced-function OCT1 alleles on any of these measures. All individuals completed the glycogen depleting fast without hypoglycaemia. CONCLUSIONS/INTERPRETATION: Metformin stimulates glycolytic glucose utilisation and lactate production in the glycogen depleted state. This may trigger a rise in glucose counter-regulatory hormones and subsequently an increase in EGP, which protects against hypoglycaemia. TRIAL REGISTRATION: ClinicalTrials.gov NCT01400191 FUNDING: Danish Research Council for Health and Disease (0602-02695B) and Odense University Hospital Free Research Fund, 2012. PMID- 26271345 TI - Depressed Adolescents' Pupillary Response to Peer Acceptance and Rejection: The Role of Rumination. AB - Heightened emotional reactivity to peer feedback is predictive of adolescents' depression risk. Examining variation in emotional reactivity within currently depressed adolescents may identify subgroups that struggle the most with these daily interactions. We tested whether trait rumination, which amplifies emotional reactions, explained variance in depressed adolescents' physiological reactivity to peer feedback, hypothesizing that rumination would be associated with greater pupillary response to peer rejection and diminished response to peer acceptance. Twenty currently depressed adolescents (12-17) completed a virtual peer interaction paradigm where they received fictitious rejection and acceptance feedback. Pupillary response provided a time-sensitive index of physiological arousal. Rumination was associated with greater initial pupil dilation to both peer rejection and acceptance, and diminished late pupillary response to peer acceptance trials only. Results indicate that depressed adolescents high on trait rumination are more reactive to social feedback regardless of valence, but fail to sustain cognitive-affective load on positive feedback. PMID- 26271347 TI - Reply to Letter to the Editor: Bariatric Surgery Worldwide 2013 Reveals a Rise in Mini-Gastric Bypass. PMID- 26271346 TI - Using a Brief Parent-Report Measure to Track Outcomes for Children and Teens with ADHD. AB - The Pediatric Symptom Checklist (PSC) is a widely used, parent-completed measure of children's emotional and behavioral functioning. Previous research has shown that the PSC and its subscales are responsive to patient progress over the course of psychiatric treatment. In this naturalistic study, parents and clinicians of 1736 patients aged 17 or younger completed standardized measures at intake and 3 month follow-up appointments. We assessed the 5-item PSC Attention Subscale (PSC AS) as a longitudinal measure of attention-related symptoms in routine outpatient psychiatry treatment. Secondarily, we compared PSC-AS scores with clinician reported diagnoses, psychomotor excitation symptoms, and overall functioning. Change scores on the PSC-AS were larger among patients with ADHD diagnoses than those with non-ADHD diagnoses. Comparisons between PSC-AS scores and clinician reports also showed acceptable levels of agreement. Given its effectiveness in tracking attention-related symptoms, the PSC may be particularly useful as a quality assurance or treatment outcome measure for clinicians treating ADHD. PMID- 26271348 TI - Conversion of Carbon Dioxide by Methane Reforming under Visible-Light Irradiation: Surface-Plasmon-Mediated Nonpolar Molecule Activation. AB - A novel CO2 photoreduction method, CO2 conversion through methane reforming into syngas (DRM) was adopted as an efficient approach to not only reduce the environmental concentration of the greenhouse gas CO2 but also realize the net energy storage from solar energy to chemical energy. For the first time it is reported that gold, which was generally regarded to be inactive in improving the performance of a catalyst in DRM under thermal conditions, enhanced the catalytic performance of Rh/SBA-15 in DRM under visible-light irradiation (1.7 times, CO2 conversion increased from 2100 to 3600 MUmol g(-1) s(-1)). UV/Vis spectra and electromagnetic field simulation results revealed that the highly energetic electrons excited by local surface plasmon resonances of Au facilitated the polarization and activation of CO2 and CH4 with thermal assistance. This work provides a new route for CO2 photoreduction and offers a distinctive method to photocatalytically activate nonpolar molecules. PMID- 26271350 TI - Atypical Williams syndrome in an infant with complete atrioventricular canal defect. AB - Williams-Beuren Syndrome (WBS) is a well-described microdeletion syndrome characterized by specific dysmorphic facial features, peripheral pulmonic stenosis, supravalvular aortic stenosis, hypercalcemia, feeding difficulties, gastroesophageal reflux, short stature, and specific intellectual disabilities (such as visual spatial problems). WBS is caused by 7q11.23 deletions that contain multiple genes known to contribute to the above phenotype. We report a neonate with a complete atrioventricular canal (CAVC) defect, an atypical cardiac lesion for WBS, and few typical phenotypic features of WBS, diagnosed at 20 days of life. PMID- 26271349 TI - Short CCG repeat in huntingtin gene is an obstacle for replicative DNA polymerases, potentially hampering progression of replication fork. AB - Trinucleotide repeats (TNRs) are highly unstable in genomes, and their expansions are linked to human disorders. DNA replication is reported to be involved in TNR instability, but the current models are insufficient in explaining TNR expansion is induced during replication. Here, we investigated replication fork progression across huntingtin (HTT)-gene-derived fragments using an Escherichia coli oriC plasmid DNA replication system. We found most of the forks to travel smoothly across the HTT fragments even when the fragments had a pathological length of CAG/CTG repeats (approximately 120 repeats). A little fork stalling in the fragments was observed, but it occurred within a short 3'-flanking region downstream of the repeats. This region contains another short TNR, (CCG/CGG)7 , and the sense strand containing CCG repeats appeared to impede the replicative DNA polymerase Pol III. Examining the behavior of the human leading and lagging replicative polymerases Pol epsilon (hPolepsilon) and Pol delta (hPoldelta) on this sequence, we found hPoldelta replicating DNA across the CCG repeats but hPolepsilon stalling at the CCG repeats even if the secondary structure is eliminated by a single-stranded binding protein. These findings offer insights into the distinct behavior of leading and lagging polymerases at CCG/CGG repeats, which may be important for understanding the process of replication arrest and genome instability at the HTT gene. PMID- 26271352 TI - Cluster formation in a heterogeneous metapopulation model. AB - A spatially explicit heterogeneous metapopulation model with two different patch types is analyzed. Some network topologies support a partially synchronized dynamics, a state where two different clusters of patches are formed. Within each cluster the dynamics of all patches are synchronized. The linearized asymptotic stability of the partially synchronized attractor is studied. The transversal stability is analyzed and a simple expression for the transversal Lyapunov number of partially synchronized attractors is obtained. PMID- 26271351 TI - The potential of at-home prediction of the formation of urolithiasis by simple multi-frequency electrical conductivity of the urine and the comparison of its performance with urine ion-related indices, color and specific gravity. AB - It is important to control daily diet, water intake and life style as well as monitor the quality of urine for urolithiasis prevention. For decades, many ion related indices have been developed for predicting the formation of urinary stones or urolithiasis, such as EQUILs, relative supersaturation (RSS), Tiselius indices (TI), Robertson risk factor algorithms (RRFA) and more recently, the Bonn risk index. However, they mostly demand robust laboratory analysis, are work intensive, and even require complex computational programs to get the concentration patterns of several urine analytes. A simple and fast platform for measuring multi-frequency electrical conductivity (MFEC) of morning spot urine (random urine) to predict the onset of urolithiasis was implemented in this study. The performance thereof was compared to ion-related indices, urine color and specific gravity. The concentrations of relevant ions, color, specific gravity (SG) and MFEC (MFEC tested at 1, 10, 100, 5001 KHz and 1 MHz) of 80 random urine samples were examined after collection. Then, the urine samples were stored at 4 degrees C for 24 h to determine whether sedimentation would occur or not. Ion-activity product index of calcium oxalate (AP(CaOx) EQ2) was calculated. The correlation between AP(CaOx) EQ2, urine color, SG and MFEC were analyzed. AP(CaOx) EQ2, urine color and MFEC (at 5 frequencies) all demonstrated good prediction (p = 0.01, 0.01, 0.01, respectively) for stone formation. The positive correlation between AP(CaOx) EQ2 and MFEC is also significant (p = 0.01). MFEC provides a good metric for predicting the onset of urolithiasis, which is comparable to conventional ion-related indices and urine color. This technology can be implemented with much ease for objectively monitoring the quality of urine at points-of-care or at home. PMID- 26271353 TI - Protein dynamics and the all-ferrous [Fe4 S4 ] cluster in the nitrogenase iron protein. AB - In nitrogen fixation by Azotobacter vinelandii nitrogenase, the iron protein (FeP) binds to and subsequently transfers electrons to the molybdenum-FeP, which contains the nitrogen fixation site, along with hydrolysis of two ATPs. However, the nature of the reduced state cluster is not completely clear. While reduced FeP is generally thought to contain an [Fe4 S4 ](1+) cluster, evidence also exists for an all-ferrous [Fe4 S4 ](0) cluster. Since the former indicates a single electron is transferred per two ATPs hydrolyzed while the latter indicates two electrons could be transferred per two ATPs hydrolyzed, an all-ferrous [Fe4 S4 ](0) cluster in FeP is potenially two times more efficient. However, the 1+/0 reduction potential has been measured in the protein at both 460 and 790 mV, causing the biological significance to be questioned. Here, "density functional theory plus Poisson Boltzmann" calculations show that cluster movement relative to the protein surface observed in the crystal structures could account for both measured values. In addition, elastic network mode analysis indicates that such movement occurs in low frequency vibrations of the protein, implying protein dynamics might lead to variations in reduction potential. Furthermore, the different reductants used in the conflicting measurements of the reduction potential could be differentially affecting the protein dynamics. Moreover, even if the all-ferrous cluster is not the biologically relevant cluster, mutagenesis to stabilize the conformation with the more exposed cluster may be useful for bioengineering more efficient enzymes. PMID- 26271354 TI - Prescription Opioid and Benzodiazepine Use After Road Traffic Injury. AB - BACKGROUND: Motor vehicle crash victims with physical injury are likely to receive prescription opioids and benzodiazepines. Potential mental trauma and lack of primary treating physician contribute to the risk of adverse opioid outcomes for this group. The purpose of this study is to characterise opioid and benzodiazepine prescribing after road traffic injury. METHOD: Individuals who claimed Transport Accident Commission compensation for a noncatastrophic injury that occurred between 2010 and 2012 in Victoria, Australia and who provided consent for pharmaceutical benefits scheme (PBS) linkage were included (n = 734). PBS records dating between 12 months preinjury and 18 months postinjury were provided by the Department of Human Services. RESULTS: In the year before injury, 10.5% of participants received prescription opioids; after injury, 45.1% of hospitalized and 21.1% of nonhospitalized participants received opioids. Benzodiazepines were used by 4.8% preinjury, and 7.0% and 7.4% postinjury (with and without hospitalization, respectively). Postinjury, 39% of opioid use and 73% of benzodiazepine use was potentially unrelated to the injury. CONCLUSIONS: Prescription opioid and benzodiazepine before road traffic injury was substantial: the significance of postinjury prescription drug use cannot be established without taking preinjury use into account. It may be beneficial for pain medication to be managed by a pain treatment coordinator, in this injured population with high rates of pre-existing opioid and benzodiazepine use. PMID- 26271355 TI - Gelfoam embolization or 125I seed implantation may be a more effective treatment than surgical treatment for giant benign sacral neurogenic tumors. AB - BACKGROUND: The goal of the present study was to assess the effects of computed tomography (CT)-guided iodine-125 (125I) seed implantation or gelatin sponge particle (GSP) embolization on patients with giant benign sacral neurogenic tumors. METHODS: A total of 24 cases with giant sacral neurogenic tumor were performed in a retrospective study between 2000 and 2012. Nineteen cases received surgical resection, and five cases received non-surgical treatment. In surgical group, patients with type III sacral tumor had received a combined anterior posterior approach and patients with type IV were treated with simple anterior approach. In non-surgical group, CT-guided 125I seed implantation or GSP embolization was applied to occlude vessels. Besides, CT scanning or magnetic resonance imaging was used to assess the size and development of tumors. RESULTS: Two of the five patients were treated three times with GSP embolization, one had received GSP embolization combined with CT-guided 125I seed implantation, one case did not receive any treatment, and one patient was lost to follow-up. Patients in non-surgical group were followed up for 2-8 years. CONCLUSIONS: Our study suggested that CT-guided 125I seed implantation or GSP embolization treatment is very useful to slow down the development of giant benign sacral neurogenic tumors. PMID- 26271356 TI - Integrated disaster relief logistics: a stepping stone towards viable civil military networks? AB - The twenty-first century has seen a significant rise in all forms of disasters and this has resulted in military and humanitarian organisations becoming more frequently engaged in the provision of support to those affected. Achieving an efficient and effective logistic preparation and response is one of the key elements in mitigating the impact of such events, but the establishment of mechanisms to deliver an appropriately integrated civil-military approach remains elusive. Not least because of the high percentage of assistance budgets spent on logistics, this area is considered to represent fertile ground for developing improved processes and understanding. In practice, the demands placed on civilian and military logisticians are broadly similar, as is the solution space. Speaking a common language and using common concepts, it is argued, therefore, that the logistic profession should be in the vanguard of the development of an improved civil-military interface. PMID- 26271357 TI - Improved survival with early adjuvant chemotherapy after colonic resection for stage III colonic cancer: A nationwide study. AB - BACKGROUND AND OBJECTIVES: In stage III colonic cancer, time from surgery to start of adjuvant chemotherapy may influence survival. In this study, we evaluated the effect of timing of adjuvant therapy on survival. METHODS: Database study from the Danish Colorectal Cancer Group's national database. Data on patients with stage III colonic cancer operated between January 1, 2005 and August 31, 2012 were retrieved. Perioperative variables, surgical modality, and time to adjuvant therapy (<4, 4-8, or >8 weeks) were evaluated and Cox regression was performed to identify factors influencing survival. RESULTS: The final population included 1,827 patients scheduled for adjuvant chemotherapy. Adjuvant therapy started within 4 and 8 weeks improved survival when compared to start later than 8 weeks (HR [95%CI]: 1.7 [1.1-2.6]; P = 0.024 and 1.4 [1.07-1.8]; P = 0.013, respectively), whereas there was no significant difference in survival with start after 4 versus 8 weeks (1.2 [0.8-1.8]; P = 0.37). CONCLUSIONS: Survival increased when adjuvant therapy was started within 8 weeks after surgery for stage III colonic cancer. PMID- 26271360 TI - Executive inhibition: A study of postcommission error slowing and postomission error speeding. AB - Error detection, error regulation, and the way of facilitating regulation are fundamental to successful adaptation to the environment. Previous studies have demonstrated the cognitive process that underlies error detection, but it is still not clear whether this cognitive process is influenced by internal and external factors of error type and feedback. The purpose of this study was to investigate the regulation of commission and omission errors in executive inhibition tasks and the effects of feedback on error regulation. Three tasks, including a go/no-go task with visual feedback, a go/no-go task with auditory feedback, and a stop signal task with visual feedback were conducted separately with three independent groups of healthy university students. We found postcommission error slowing and postomission error speeding in the reaction times. Correct visual feedback increased all the reaction times for executive inhibition compared with incorrect feedback. The results indicated that the regulation of reaction time after different types of error may be an adaptive behavioral manifestation and that performance feedback facilitates overall inhibitory control. PMID- 26271359 TI - Prebiotic effects of diet supplemented with the cultivated red seaweed Chondrus crispus or with fructo-oligo-saccharide on host immunity, colonic microbiota and gut microbial metabolites. AB - BACKGROUND: Gastrointestinal microbial communities are diverse and are composed of both beneficial and pathogenic groups. Prebiotics, such as digestion-resistant fibers, influence the composition of gut microbiota, and can contribute to the improvement of host health. The red seaweed Chondrus crispus is rich in dietary fiber and oligosaccharides, however its prebiotic potential has not been studied to date. METHODS: Prebiotic effects were investigated with weaning rats fed a cultivated C. crispus-supplemented diet. Comparison standards included a fructo oligo-saccharide (FOS) diet and a basal diet. The colonic microbiome was profiled with a 16S rRNA sequencing-based Phylochip array. Concentrations of short chain fatty acids (SCFAs) in the feacal samples were determined by gas chromatography with a flame ionization detector (GC-FID) analysis. Immunoglobulin levels in the blood plasma were analyzed with an enzyme-linked immunosorbent assay (ELISA). Histo-morphological parameters of the proximal colon tissue were characterized by hematoxylin and eosin (H&E) staining. RESULTS: Phylochip array analysis indicated differing microbiome composition among the diet-supplemented and the control groups, with the C. crispus group (2.5% supplementation) showing larger separation from the control than other treatment groups. In the 2.5% C. crispus group, the population of beneficial bacteria such as Bifidobacterium breve increased (4.9-fold, p=0.001), and the abundance of pathogenic species such as Clostridium septicum and Streptococcus pneumonia decreased. Higher concentrations of short chain fatty acids (i.e., gut microbial metabolites), including acetic, propionic and butyric acids, were found in faecal samples of the C. crispus-fed rats. Furthermore, both C. crispus and FOS supplemented rats showed significant improvements in proximal colon histo-morphology. Higher faecal moisture was noted in the 2.5% C. crispus group, and elevated plasma immunoglobulin (IgA and IgG) levels were observed in the 0.5% C. crispus group, as compared to the basal feed group. CONCLUSIONS: The results suggest multiple prebiotic effects, such as influencing the composition of gut microbial communities, improvement of gut health and immune modulation in rats supplemented with cultivated C. crispus. PMID- 26271358 TI - Impact of the early use of immunomodulators or TNF antagonists on bowel damage and surgery in Crohn's disease. AB - BACKGROUND: The impact of early treatment with immunomodulators (IM) and/or TNF antagonists on bowel damage in Crohn's disease (CD) patients is unknown. AIM: To assess whether 'early treatment' with IM and/or TNF antagonists, defined as treatment within a 2-year period from the date of CD diagnosis, was associated with development of lesser number of disease complications when compared to 'late treatment', which was defined as treatment initiation after >2 years from the time of CD diagnosis. METHODS: Data from the Swiss IBD Cohort Study were analysed. The following outcomes were assessed using Cox proportional hazard modelling: bowel strictures, perianal fistulas, internal fistulas, intestinal surgery, perianal surgery and any of the aforementioned complications. RESULTS: The 'early treatment' group of 292 CD patients was compared to the 'late treatment' group of 248 CD patients. We found that 'early treatment' with IM or TNF antagonists alone was associated with reduced risk of bowel strictures [hazard ratio (HR) 0.496, P = 0.004 for IM; HR 0.276, P = 0.018 for TNF antagonists]. Furthermore, 'early treatment' with IM was associated with reduced risk of undergoing intestinal surgery (HR 0.322, P = 0.005), and perianal surgery (HR 0.361, P = 0.042), as well as developing any complication (HR 0.567, P = 0.006). CONCLUSIONS: Treatment with immunomodulators or TNF antagonists within the first 2 years of CD diagnosis was associated with reduced risk of developing bowel strictures, when compared to initiating these drugs >2 years after diagnosis. Furthermore, early immunomodulators treatment was associated with reduced risk of intestinal surgery, perianal surgery and any complication. PMID- 26271361 TI - Cognitive functioning and cortisol suppression in recurrent major depression. AB - Major Depressive Disorder (MDD) is often associated with high levels of stress and disturbances in the hypothalamic-pituitary-adrenal (HPA) system, yielding high levels of cortisol in addition to cognitive dysfunction. The aim of the present study was to examine the relation between cortisol levels after the dexamethasone suppression test and cognitive function in recurrent unipolar MDD patients. Twenty-four patients meeting the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) criteria for a recurrent MDD diagnosis were included in the study. The control group was matched for age, sex, and education level. Cortisol was measured in saliva collected with Salivette sampling devices. Saliva samples were collected four times during a 24-hr period over two consecutive days: at awakening, after 45 min, after 7 hr, and at 11:00 p.m. One milligram of dexamethasone was given on Day 1 at 11:00 p.m. The neuropsychological test battery consisted of standardized tests measuring cognitive functioning within verbal and visual memory, as well as executive functioning. Cortisol levels did not differ between patients and controls on Day 1. Cortisol levels in patients were higher than in controls at awakening on Day 2 (D2S1), after dexamethasone administration the previous evening. All significant correlations between cognitive measures and cortisol at D2S1 were negative, indicating that low suppression after intake of dexamethasone is related to poor cognitive functioning. Significant relations were found in three of the cognitive tests measuring verbal memory, semantic fluency, and inhibition. The present findings indicate that dysregulation of the HPA-axis is related to poor verbal memory functioning. There was no firm evidence that abnormal cortisol levels were associated with inhibition difficulties. PMID- 26271363 TI - Markers of good planning behavior as a cue for separating true and false intent. AB - The study adds to the growing body of research on true and false intentions, traditionally a neglected area of deception research. Specifically, the goal was to examine the claim that statements of true intent would be colored by markers of good planning behavior to a greater extent than statements of false intent. Participants (N = 132) were divided into truth tellers and liars. Truth tellers were given a neutral task to plan and carry out. Liars were given a mock crime to plan and carry out and were also told to plan a cover story to be used in case they were apprehended. The cover story (i.e., liars' false intention) was to be thematically similar to the truth tellers' task. Following the planning phase, but before the task commenced, participants were interviewed about their intent. Transcribed interviews were coded for markers of good planning behavior (e.g., effective time allocation, implementation intention related utterances, and likelihood to speak of potential problems). As predicted, truth tellers' statements were colored to a higher degree than those of liars by such markers. The results earmark this approach as a viable direction for future research. PMID- 26271362 TI - The nature and extent of working memory dysfunction in schizophrenia. AB - This study aimed to examine verbal and visual-spatial working memory (WM) dysfunction in patients with schizophrenia. We compared 60 patients with schizophrenia with 57 healthy controls (matched for age, educational level, and IQ) on three WM tasks. Patients with schizophrenia performed significantly more poorly than healthy controls on verbal, visual, and spatial WM tests. Moreover, WM deficits were inversely associated with both the positive and negative symptoms of the patients. Taken together, these findings suggest that there are pervasive WM impairments in patients with schizophrenia. In addition, clinical features may play a significant role in the expression of WM deficits. PMID- 26271364 TI - Privatizing health care in times of new public management: Investigating the role of psychological empowerment using cluster analysis. AB - Although privatization within health care is usually justified using arguments based on efficiency and productivity, the empirical investigations underpinning such arguments are few and ambiguous in their results. Presenting a new theoretical and analytical approach to this research field, we argue that psychological empowerment, reflecting individuals' intrinsic change motivation state, is a crucial prerequisite for the transformation of a nonprofit health care organization to a for-profit one. The general aims of this study were to explore empowerment cognitions during a privatization, to relate these to a selection of key work-related outcome variables, and to identify the effects of privatization in terms of individual level changes in empowerment after privatization. A sample of health care workers (n = 210) provided survey longitudinal data that were analyzed using cluster analysis. Eight clusters were identified at both pre- and postprivatization with each cluster mirroring specific empowerment patterns: Empowered, In Control, Quasi-Empowered, Competent/Normed, Reference, Underused, Misfit, and Powerless. The clusters discriminated on positive work attitudes, mental health complaints, and turnover intentions. The analysis also revealed the complexity of privatization in that a homogenization as well as a differentiation tendency was observed, thereby implicating both socio-structural equality and inequality effects. The results highlighted the relevance of allocating importance to health care workers' psychological empowerment during the privatization process, and of viewing such organizational transformations not as simple shifts in the state of affairs, but as nonlinear processes involving dynamic changes in individual perceptions over time. PMID- 26271365 TI - Self-image in adolescents with deliberate self-harm behavior. AB - This study tested the hypothesis of a positive relation between deliberate self harm and poor self-image in adolescents and investigated the relation between substance abuse (drugs, cigarettes, and alcohol) and deliberate self-harm. One hundred thirteen high-school students, aged predominantly 16-18 years, responded to the 16-item version of the Deliberate Self-Harm Inventory, the 36-item Structural Analysis of Social Behavior, and single questions about use of drugs, cigarettes, and alcohol. The results showed a positive relation between deliberate self-harm and poor self-image, and between deliberate self-harm and cigarette smoking and alcohol consumption. These results imply that poor self image and a large extent of substance use may be markers for identifying adolescents at risk for deliberate self-harm. PMID- 26271366 TI - Profilin Expression Is Regulated by Bone Morphogenetic Protein (BMP) in Osteoblastic Cells. AB - Profilin 1 (Pfn1) regulates cytoskeletal reorganization and migration, but its role in osteoblasts is not known. BMP (bone morphogenetic protein) is a multifunctional cytokine involved in osteoblastic differentiation and promotes bone regeneration and repair. Although several molecules are known to modulate BMP signaling, mechanisms that determine the levels of BMP action in osteoblastic function are still incompletely understood. We therefore examine the expression of Pfn1 in osteoblasts and its role in BMP-induced differentiation in osteoblasts. In osteoblastic MC3T3-E1(MC) cells, Pfn1 mRNA is expressed constitutively and its expression levels are declined during the culture in a time dependent manner in contrast to the increase in alkaline phosphatase activity revealing that Pfn1 expression is down regulated along with differentiation. To test the effects of osteoblastic differentiation on Pfn1expression further, MC cells are treated with BMP. BMP treatment suppresses the levels of Pfn1 mRNA. This suppressive effect of BMP is time dependent and further down regulation of Pfn1 mRNA levels is observed when the BMP treatment is continued for a longer period of time. Pfn1mRNA knock down (KD) by siRNAs enhances BMP-induced increase in alkaline phosphatase (Alp) activity in MC cells. To analyze the regulatory mechanism, Alp mRNA levels are examined and Pfn1 KD enhances the BMP-induced increase in the levels of Alp mRNA expression. Furthermore, Pfn1 KD enhances BMP-induced transcriptional expression of luciferase reporter activity via BMP response element in osteoblasts. These data indicate that Pfn1 is a novel target of BMP and suppresses BMP-induced differentiation of osteoblasts at least in part via transcriptional event. PMID- 26271368 TI - Government Quality Measures: First Do No Harm. AB - A technical expert panel (TEP) was convened to evaluate all available literature in the area of bone and mineral metabolism and advise the Centers for Medicare and Medicaid services on the creation and collection of quality measures. The proposed quality measures were evaluated for importance, usability, feasibility, and scientific acceptability. All are important parameters to avoid unintended harmful consequences of a quality measure causing harm to patients or to the delivery of their health care. PMID- 26271367 TI - Is preoperative state anxiety a risk factor for postoperative delirium among elderly hip fracture patients? AB - AIM: To determine if preoperative state anxiety is a risk factor for postoperative delirium in older hip fracture patients. METHODS: A secondary data analysis comprising data from a prospective non-randomized trial including 86 patients with a hip fracture aged 65 years and older was carried out. State anxiety was measured preoperatively using the State-Trait Anxiety Inventory. Delirium and its severity was measured pre- and postoperatively (day 1, 3, 5, 8) by trained research nurses using the Confusion Assessment Method and Delirium Index. RESULTS: A total of 24 patients (27.9%) developed delirium postoperatively. Preoperative state anxiety (State-Trait Anxiety Inventory) was not associated with postoperative delirium (rb = 0.135, P = 0.353), duration of postoperative delirium (rho = 0.038, P = 0.861) or severity of postoperative delirium (rho = 0.153, P = 0.160). Independent predictors of postoperative delirium were lower MMSE scores (OR 0.75, 95% CI 0.60-0.95, P = 0.015), osteosynthesis surgery (OR 3.66, 95% CI 1.02-13.15, P = 0,047) and lowest intraoperative diastolic blood pressure (OR 0.92, 95% CI 0.85-0.99, P = 0.031). CONCLUSION: No relationship between state anxiety and postoperative delirium was found, but significant methodological hurdles were observed and discussed providing important groundwork for further research in this area. Further research should focus on reliable measurement of state anxiety in cognitively impaired older populations. Geriatr Gerontol Int 2016; 16: 948-955. PMID- 26271369 TI - Highly selective two-photon imaging of cysteine in cancerous cells and tissues. AB - Abnormal concentrations of Cys have been reported to be implicated in various health problems, including cancer, neuropathy, and cardiomyopathy. We present a novel two-photon fluorescent probe for the specific recognition of cysteine over homocysteine and glutathione, and the bioapplication of this probe for the imaging of live cancerous cells and thick tissues. PMID- 26271370 TI - Preference-based health-related quality of life among victims of bullying. AB - PURPOSE: No previous study has estimated the association between bullying and preference-based health-related quality of life (HRQoL) ("utility"), knowledge of which may be used for cost-effectiveness studies of interventions designed to prevent bullying. Therefore, the aim of the study was to estimate preference based HRQoL among victims of bullying compared to non-victims. METHODS: A cross sectional survey data collection among Swedish adolescents aged 15-17 years in the first year of upper secondary school was conducted in the city of Gothenburg in Sweden (N = 758). Preference-based HRQoL was estimated with the SF-6D. Regression analyses were conducted to adjust for some individual-level background variable. RESULTS: Mean preference-based health-related quality of life scores were 0.77 and 0.71 for non-victims and victims of bullying, respectively. The difference of 0.06 points was statistically significant (p < 0.05) and robust to inclusion of gender, age, and parental immigrant status. CONCLUSIONS: The preference-based HRQoL estimates in this study may be used as an upper bound in economic evaluations of bullying prevention interventions, facilitating a comparison between costs and quality-adjusted life-years. PMID- 26271372 TI - Formalism and functionalism in linguistics. AB - Formalism and functionalism in linguistics are often taken to be diametrically opposed approaches. However, close examination of the relevant phenomena reveals that the two are complementary, rather than being irrevocably in opposition to each other. One can be a formal linguist and a functional linguist at the same time, without there being any contradiction. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271373 TI - Adaptation to sensory loss. AB - The human brain has the remarkable ability to adapt to changes in its environment by benefiting from its 'plastic' properties. Following brain injury, the amputation of a limb, or the loss of a sensory input such as peripheral blindness, brain circuitry often seems to be able to reorganize itself in order to compensate for the handicap by being recruited to carry out tasks not associated with their prior 'default' functioning. The purpose of this review is to illustrate the brain's remarkable ability to adapt to changes in its environment, particularly when it is faced with a sensory loss. Two excellent models to study this phenomenon are provided by blind and deaf individuals. In both cases, studies have shown that they appear to compensate for the loss of sensory input with enhanced abilities in their remaining senses. These behavioral modifications are often coupled with changes in cerebral processing, generally in the form of crossmodal recruitment of deaffarented primary and secondary sensory areas. We will also discuss the possible mechanisms underlying these changes and whether the functional topography of these regions present in unimpaired individuals is preserved in blindness and deafness. The notion of a critical period for plastic changes will also be discussed and its importance will be shown to be twofold. On the one hand, the functional relevance of crossmodal processing appears to decrease as a function of the age of onset of the deficiency. On the other hand, the more cortical reorganization takes place, the less likely brain areas will be able to process input from its original sensory modality. This is especially important for deaf individuals as auditory input can now be restored thanks to cochlear implants. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271371 TI - Pharmacokinetic interaction between the CYP3A4 inhibitor ketoconazole and the hormone drospirenone in combination with ethinylestradiol or estradiol. AB - AIMS: The present study was conducted to investigate the influence of the strong CYP3A4 inhibitor ketoconazole (KTZ) on the pharmacokinetics of drospirenone (DRSP) administered in combination with ethinylestradiol (EE) or estradiol (E2). METHODS: This was a randomized, multicentre, open label, one way crossover, fixed sequence study with two parallel treatment arms. A group sequential design allowed terminating the study for futility after first study cohort. About 50 healthy young women were randomized 1 : 1 to 'DRSP/EE' or 'DRSP/E2'. Subjects in the 'DRSP/EE' group received DRSP 3 mg/EE 0.02 mg (YAZ(r), Bayer) once daily for 21 to 28 days followed by DRSP 3 mg/EE 0.02 mg once daily plus KTZ 200 mg twice daily for 10 days. Subjects in the 'DRSP/E2' group received DRSP 3 mg/E2 1.5 mg (research combination) once daily for 21 to 28 days followed by DRSP 3 mg/E2 1.5 mg once daily plus KTZ 200 mg twice daily for 10 days. RESULTS: Oral co administration of DRSP/EE or DRSP/E2 and KTZ resulted in an increase in DRSP exposure (AUC(0,24 h)) in both treatment groups: DRSP/EE group: 2.68-fold DRSP increase (90% CI 2.44, 2.95); DRSP/E2 group: 2.30-fold DRSP increase (90% CI 2.08, 2.54). EE and estrone (metabolite of E2) exposures were increased ~1.4-fold whereas E2 exposure was largely unaffected by KTZ co-administration. CONCLUSIONS: A moderate pharmacokinetic drug-drug interaction between DRSP and KTZ was demonstrated in this study. No relevant changes of medical concern were detected in the safety data collected in this study. PMID- 26271374 TI - Learning sciences. AB - The aims of the learning sciences (LS) are to understand the nature of learning from a broad range of perspectives, and to shape the ways that learning environments and resources are designed and used. LS incorporates both systemic and elemental approaches to investigating questions about learning, as a complement to the primarily elemental approach emphasized in cognitive science research. Thus, its greatest potential is in the integration of systemic and elemental perspectives. Four major themes are central. First, research in LS attempts to bridge the divide between research and practice. Second, research in LS is motivated by limitations of theories of learning and cognition for specifying instruction. Third, research in LS embraces the importance of analyzing and assessing complex interventions through both experimental and design-based research. Fourth, research in LS emphasizes the learning and behavior of the individual in interaction with the physical, social, and cultural world, as well as with semiotic and technical resources. Research in LS can be conceptualized along a continuum of time scales, from the more microscopic to the more macroscopic. The time-scale framework illustrates how disparate research traditions and research methods can function within a unifying framework for the study of learning and complex behavior. The effort to 'scale-up' from more elemental findings to more complex, authentic settings has been generative for LS, but faces serious challenges. There is an alternate route to establishing a cumulative scientific knowledge base, namely, 'scaling down' from more complex, ecologically valid levels to more elemental levels. Studies of basic learning processes, framed in the context of the larger system, are well positioned to support impact in authentic settings. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271375 TI - Aging and cognition. AB - As we grow older, we gain knowledge and experience greater emotional balance, but we also experience memory loss and difficulties in learning new associations. Which cognitive abilities decline, remain stable or improve with age depends on the health of the brain and body as well as on what skills are practiced or challenged in everyday life. Recent research provides a growing understanding of the relationship between physical and cognitive changes across the life span and reveals ways to increase mental sharpness and avoid cognitive decline. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271376 TI - Desire: philosophical issues. AB - To desire something is to want it, wish it, long for it. Various leading theories of this attitude exist, with the most prominent theory holding that to desire something is nothing more than to be inclined to take actions that will obtain that thing. Other important theories tie desires to pleasure and displeasure, to reasons and goodness, or to reward learning. All of these theories leave room for scientific investigation of what causes us to desire, and of what else desires might cause in us. Philosophical speculation on these topics has focused, in the former case, on the generation of new desires from existing desires. In the latter case, it has roamed across topics diverse as the influence of desire on cognition, the relation of desire to mental disorder, and causation of self knowledge of one's own desires. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271377 TI - Discourse processing-examining our everyday language experiences. AB - Studies of discourse processing focus on the ways in which readers and listeners comprehend language. The linguistic segments of interest to the field tend to be larger than sound, word, or sentence-level units; they include the books and conversational communications that comprise our everyday cognitive and social interactions. The current review focuses on discourse comprehension (specifically text processing), highlighting three core issues of primary interest to the research field. First, we outline the particular elements that make up naturalistic discourse activity. Second, we identify potential interactions among the elements, and how investigations of these interactions have resulted in influential frameworks for the field. Finally, we examine contemporary work (both theoretical and applied) that might further enhance current accounts of discourse processing. As appropriate, the review includes references to relevant empirical research outlining the processes that guide, and are guided by, our discourse experiences. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271378 TI - Two systems of reasoning: architecture and relation to emotion. AB - Distinguishing cognitive systems that support intuition and deliberation has proven necessary to explain how people reason,1, 2 decide,3 categorize,4 form attitudes,5 make confidence6 and moral7 judgments, and prioritize goals.8 Both behavioral and neuroimaging evidence show that the evidence supports similar distinctions in each field. Deliberative processing enlists working memory, and intuitive processing depends more directly on long-term memory retrieval. One of the key unanswered questions concerns how the systems interact. The data suggest that one of the key functions of deliberation is to suppress intuition. It does not invariably succeed, however, and leakage is common. Another question concerns the relations between affect and reasoning systems. The evidence suggests that emotions are not exclusively related to the intuitive system. Instead, emotional reactions that are directly tied to the perception of objects and events (e.g., fear) are associated with intuition, emotions that arise when alternative possibilities are considered (e.g., regret) are tied to deliberation, and moods (e.g., happy, sad) influence how much each system is relied on. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271379 TI - Unraveling the paradox of the autistic self. AB - Paradoxically, individuals with autism spectrum conditions have been characterized as both impaired in self-referential cognitive processing, yet also egocentric. How can the self in autism be both 'absent' (i.e., impaired self referential cognition), yet 'all too present' (i.e., egocentric)? In this paper, we first review evidence in support of both claims. Second, we highlight new evidence illustrating atypical function of neural systems underlying self representation in autism. We suggest that egocentrism and impaired self referential cognition are not independent phenomena. Instead, both egocentrism and impaired self-referential cognition in autism can be resolved as expressions of one common mechanism linked to the atypical function of neural circuitry coding for self-relevant information. We discuss how autism provides a unique window into the neurodevelopmental mechanisms enabling a critical developmental transition in self-awareness. This transition involves a dual understanding that one is similar to, yet distinct from others. The neural and cognitive basis of this developmental transition is central to understanding the development of social cognition as well as the paradox of the autistic self and its relation to social impairment in autism. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271380 TI - Expertise. AB - The study of expertise is based on the premise that experts in different domains follow a similar path of acquisition and development. This article distinguishes two research approaches to the study of expertise. The traditional approach assumes a steady progression from novice to expert as a function of training as well as years of experience often without measures of reproducible skill. A second and more recent one focuses on the identification of individuals with reproducibly superior performance for representative tasks that capture expertise in the domain. The focus of this review is on the latter, namely the expert performance approach. The article describes how superior performance can be captured by standardized tasks, and how analyses of that superior performance can identify superior abilities, cognitive mechanisms, and physiological adaptations. The last part of the article reviews how deliberate practice and training can lead to the acquisition of complex mechanisms and physiological adaptations, which in turn can explain the experts' attained superior performance. The review is concluded with a discussion of future directions of studies of expert performance and the challenges in understanding the development of general abilities and the motivation to engage in sustained daily deliberate practice. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271381 TI - The development of emotion. AB - Given that they are responsible for much of the meaning that we attribute to our existence, emotions could be said to have a central role in the psychological life of humans. But given this fundamental level of significance, the construct of emotion remains poorly understood, with the field of emotion research being full of conflicting definitions and opposing theoretical perspectives. In this review, one particular aspect of research into emotion is considered: the development of emotion in infancy and early childhood. The development of the emotional life of the child has been the focus of a vast amount of research and theorizing, so in a brief review it is only possible to scratch the surface of this topic. Rather than any attempt at a comprehensive account, three perennial questions in theorizing and research on early emotional development will be considered. First, what develops in emotional development? Second, what is the relation of cognitive development to emotional development? Third, how has the study of early individual differences in emotion expression typically been approached? In relation to the first question, four theoretical approaches to emotional development are described. For the second question, the focus is on the relation of self-awareness to the development of emotion. Finally, for the third question, the use of temperament theory as a framework for understanding individual differences in emotion expression is examined. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271383 TI - Asymmetry of interhemispheric communication. AB - The role of the corpus callosum (CC) in ensuring communication between the cerebral hemispheres is an undisputed great discovery of the 20th century. In the past 20 years, it has been repeatedly shown by behavioral and electrophysiological experiments that callosal transmission is asymmetric. It is faster from the right to the left hemispheres for a host of behavioral and cognitive processes. The functional meaning and the neural bases of the asymmetry are still being investigated but one possibility is that it is related to a larger proportion of cortical neurones, projecting their axon from the right to the left hemisphere than in the reverse direction in the CC. This asymmetry might be related to the necessity to rapidly access the left hemisphere for response during tasks mainly subserved by the right hemisphere. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271382 TI - Dyslexia (neuropsychological). AB - In this article, we review research into the underlying deficits associated with the failure to learn to read normally, or developmental dyslexia. We focus on the heterogeneity within this broad category of disorder and on the relationship between the proposed deficits and the acquisition of specific kinds of reading skill. We also distinguish between 'high-level' cognitive or language deficits associated with developmental dyslexia and 'low-level' perceptual or neurological deficits. We conclude that the mixed and sometimes contradictory sets of findings associated with most of the proposed deficits reveal something important: that there is no single cause of developmental dyslexia and that it is likely that multiple causes interact in complex ways to impair reading acquisition. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271384 TI - Cognition and animal welfare. AB - Animals exhibit species-typical adaptations of behavior and may suffer stress in captivity if they are prevented from performing these patterns of behavior. This article considers whether these particular 'needs' rely on cognitive processes or are performed without complex cognition despite their appearance of behavioral complexity. Emotion and cognition in animals are also discussed, particularly whether animals can feel emotions and, if so, what ranges of emotions they might feel. Cognitive capacities that would contribute to suffering include empathy with the suffering of others, memories of negative events and suffering in anticipation of future events. Cognitive bias of individual animals toward positive or negative feelings is related to dominance of the left or right hemisphere, respectively. These biases might be reflected in the animal's preferred limb to pick up food. Hence, limb preference could be a useful measure of cognitive bias. Post-traumatic stress disorder is a cognitive condition that, it is suggested, might involve dominance of the right hemisphere. This debilitating condition is experience-dependent and not infrequently seen in animals in captivity. In conclusion, it is argued that there is an obvious need for more research on cognition as it relates to animal welfare and as a basis for changing legislature to protect animals from suffering. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271385 TI - The Influence of New Technologies on the Visual Attention of CSIs Performing a Crime Scene Investigation. AB - Currently, a series of promising new tools are under development that will enable crime scene investigators (CSIs) to analyze traces in situ during the crime scene investigation or enable them to detect blood and provide information on the age of blood. An experiment is conducted with thirty CSIs investigating a violent robbery at a mock crime scene to study the influence of such technologies on the perception and interpretation of traces during the first phase of the investigation. Results show that in their search for traces, CSIs are not directed by the availability of technologies, which is a reassuring finding. Qualitative findings suggest that CSIs are generally more focused on analyzing perpetrator traces than on reconstructing the event. A focus on perpetrator traces might become a risk when other crime-related traces are overlooked, and when analyzed traces are in fact not crime-related and in consequence lead to the identification of innocent suspects. PMID- 26271386 TI - The isoforms generated by alternative translation initiation adopt similar conformation in the selectivity filter in TREK-2. AB - TREK-2 (TWIK-related K(+) channel-2), a member of two-pore domain potassium (K2P) channel family, tunes cellular excitability via conducting leak or background currents. In TREK-2, the isoforms generated by alternative translation initiation (ATI) mechanism exhibit large divergence in unitary conductance, but similar in selectivity to K(+). Up to now, the structural basis for this similarity in ion selectivity is unknown. Here, we report that externally applied Ba(2+) inhibits the currents of TREK-2 in a concentration- and time-dependent manner. The blocking effect is blunted by elevated extracellular K(+) or mutation of S4 K(+) binding site, which suggests that the inhibitory mechanism of Ba(2+) is due to its competitive docking properties within the selectivity filter (SF). Next, we demonstrate that all the ATI isoforms exhibit analogous behaviors upon the application of Ba(2+) and alteration of extracellular pH (pHo), which acts on the outer position of the SF. These results strongly support the notion that all the ATI isoforms of TREK-2 possess resembled SF conformation in S4 site and the position defined by pHo, which implicates that neither the role of N-terminus (Nt) nor the unitary conductance is associated with SF conformation. Our findings might help to understand the detail gating mechanism of TREK-2 and K2P channels. PMID- 26271387 TI - Paradoxical Expansion of Th1 and Th17 Lymphocytes in Rheumatoid Arthritis Following Infliximab Treatment: a Possible Explanation for a Lack of Clinical Response. AB - PURPOSE: The immunogenicity of anti-TNF-alpha drugs may affect their safety and efficacy. Infliximab (IFX), a chimeric monoclonal antibody, induces antibody formation in up to 60% of cases. Some studies have suggested the involvement of a Th1 response to TNFalpha blockers following immunization, but the triggering of Th17 responses has never been reported. The aim of this study is to investigate whether the immunogenicity of IFX affects the Th1, Th17 and Treg compartments in rheumatoid arthritis (RA) patients failing IFX therapy, and verify whether this may be responsible for treatment failure. METHODS: The study involved 55 patients with RA (15 treatment-naive patients; 20 IFX responders; 20 IFX non-responders) and 10 healthy controls. PBMCs were cultured in the presence/absence of IFX, and the variations in the percentage of Th1, Th17 and Treg lymphocytes following IFX treatment were analysed. RESULTS: IFX-specific Th1 and Th17 responses and an increase in IL-21 production were observed in patients failing IFX (p < 0.01, p < 0.05, and p < 0.01 respectively). In contrast, IFX incubation reduced significantly Th1 and Th17 responses and IL-21 production (p < 0.05) in successfully-treated subjects, but did not affect these responses in healthy controls or treatment-naive patients. CONCLUSIONS: RA patients may have impaired peripheral tolerance, which could favour the development of an aberrant immunological response to biological drugs. The loss of therapeutic effectiveness of IFX and the onset of adverse events may be due to a paradoxical activation of Th17 or Th1 lymphocytes following sensitisation, thus worsening the patients' inflammatory status. PMID- 26271388 TI - Novel Mutation in the Class II Transactivator Associated with Immunodeficiency and Autoimmunity. PMID- 26271389 TI - Validity of Primary Immunodeficiency Disease Diagnoses in United States Medicaid Data. AB - PURPOSE: Primary immunodeficiency diseases (PID) are a rare group of disorders with a wide array of clinical presentations. The absence of validated methods to identify these diseases in electronic databases has limited understanding of their epidemiology and the impact of drug therapies on outcomes. We measured the positive predictive values (PPVs) of ICD-9 diagnoses for identifying PID within US Medicaid. METHODS: We identified Medicaid patients from California, Florida, New York, Ohio, and Pennsylvania with PID ICD-9 diagnoses (common variable immunodeficiency [279.06], X-linked agammaglobulinemia [279.04], hyper immunoglobulin M syndrome [279.05], Wiskott Aldrich Syndrome [279.12]) recorded at least twice from 1999 to 2007. Outpatient records were reviewed by a clinical immunologist to adjudicate diagnoses. PPVs with 95% confidence intervals (CIs) for confirmed outcomes were determined for individual ICD-9 diagnoses and combinations of diagnoses and Current Procedural Terminology codes for a quantitative immunoglobulin test (82784) or immunoglobulin infusion (96365). RESULTS: Among 83 patients with PID ICD-9 diagnoses, 16 were adjudicated as having the condition (PPV, 19.3%; 95% CI, 11.4-29.4%). Individual ICD-9 diagnoses had low PPVs (range, 16.7-33.3%). Requiring procedural codes for quantitative immunoglobulins or intravenous immunoglobulin did not increase PPVs of these diagnoses (range, 11.1-41.7%). An X-linked agammaglobulinemia diagnosis plus intravenous immunoglobulin had the highest PPV among the algorithms evaluated (PPV, 41.7%; 95% CI, 15.1-72.3%). CONCLUSIONS: Algorithms comprising PID ICD-9 diagnoses and procedures for quantitative immunoglobulin tests and immunoglobulin infusion had low PPVs for adjudicated diagnoses in Medicaid. Alternative data sources should be evaluated to study the epidemiology of these diseases. PMID- 26271390 TI - Nijmegen Breakage Syndrome: Clinical and Immunological Features, Long-Term Outcome and Treatment Options - a Retrospective Analysis. AB - PURPOSE: Nijmegen Breakage Syndrome (NBS) is a rare inherited condition, characterized by microcephaly, chromosomal instability, immunodeficiency, and predisposition to malignancy. This retrospective study, characterizing the clinical and immunological status of patients with NBS at time of diagnosis, was designed to assess whether any parameters were useful in disease prognosis, and could help determine patients qualified for hematopoietic stem cell transplantation. METHODS: The clinical and immunological characteristics of 149 NBS patients registered in the online database of the European Society for Immune Deficiencies were analyzed. RESULTS: Of the 149 NBS patients, 91 (61%), of median age 14.3 years, remained alive at the time of analysis. These patients were clinically heterogeneous, with variable immune defects, ranging from negligible to severe dysfunction. Humoral deficiencies predisposed NBS patients to recurrent/chronic respiratory tract infections and worsened long-term clinical prognosis. Eighty malignancies, most of lymphoid origin (especially non-Hodgkin's lymphomas), were diagnosed in 42% of patients, with malignancy being the leading cause of death in this cohort. Survival probabilities at 5, 10, 20 and 30 years of age were 95, 85, 50 and 35%, respectively, and were significantly lower in patients with than without malignancies. CONCLUSIONS: The extremely high incidence of malignancies, mostly non-Hodgkin's lymphomas, was the main risk factor affecting survival probability in NBS patients. Because treatment of NBS is very difficult and frequently unsuccessful, the search for an alternative medical intervention such as hematopoietic stem cell transplantation is of great clinical importance. PMID- 26271392 TI - Measurement of ankle plantar flexor spasticity following stroke: Assessment of a new quantitative tool. AB - OBJECTIVE: To assess the ability of a newly developed portable instrument (the Electric Spastic Ankle Measure (E-SAM)) to quantitatively measure ankle plantar flexor muscle tone and spasticity. DESIGN: Comparison of quantitative measurements of the E-SAM with those obtained manually with the Modified Ashworth Scale (MAS). PARTICIPANTS: Seven adult men with stroke of more than 8 months' duration with a MAS score of 3, and 7 healthy age-matched control subjects. MAIN OUTCOME MEASURES: Quantitative measurements of the reactive and viscoelastic components of muscle tonus and spasticity. RESULTS: Analysis of the pooled data of all subjects revealed 2 components: an initial negative peak (indicating visco elasticity), and subsequent positive peaks (denoting reactive contractions of the plantar flexor muscles). Positive, reactive contraction, peaks of the subjects with stroke were significantly higher than those of age-matched controls (p<0.01, t-test). CONCLUSION: The E-SAM appears to provide meaningful information on muscle tone and spasticity that is more specific and quantitative than that obtained with the MAS. While further study is necessary, this instrument shows promise as an easy-to-use clinical and research tool for the measurement of spasticity and muscle viscosity. PMID- 26271391 TI - The impact of sleep restriction while performing simulated physical firefighting work on cortisol and heart rate responses. AB - PURPOSE: Physical work and sleep restriction are two stressors faced by firefighters, yet the combined impact these demands have on firefighters' acute stress responses is poorly understood. The purpose of the present study was to assess the effect firefighting work and sleep restriction have on firefighters' acute cortisol and heart rate (HR) responses during a simulated 3-day and 2-night fire-ground deployment. METHODS: Firefighters completed multiple days of simulated physical work separated by either an 8-h (control condition; n = 18) or 4-h sleep opportunity (sleep restriction condition; n = 17). Salivary cortisol was sampled every 2 h, and HR was measured continuously each day. RESULTS: On day 2 and day 3 of the deployment, the sleep restriction condition exhibited a significantly higher daily area under the curve cortisol level and an elevated cortisol profile in the afternoon and evening when compared with the control condition. Firefighters' HR decreased across the simulation, but there were no significant differences found between conditions. CONCLUSION: Findings highlight the protective role an 8-h sleep opportunity between shifts of firefighting work has on preserving normal cortisol levels when compared to a 4-h sleep opportunity which resulted in elevated afternoon and evening cortisol. Given the adverse health outcomes associated with chronically high cortisol, especially later in the day, future research should examine how prolonged exposure to firefighting work (including restricted sleep) affects firefighters' cortisol levels long term. Furthermore, monitoring cortisol levels post-deployment will determine the minimum recovery time firefighters need to safely return to the fire-ground. PMID- 26271393 TI - Skin Reduction Nipple-Sparing Mastectomy. AB - Nipple-sparing mastectomy has been shown to be a safe and effective treatment for many patients with early stage breast cancer. Large-breasted women who are gene positive or who have early breast cancer are not traditionally candidates for nipple-sparing mastectomy. The blood supply to the nipple is via the breast tissue and also the dermis, both of which would be severed if standard skin reduction were combined with mastectomy. This video shows how a nipple-sparing mastectomy can be combined with skin reduction while preserving the blood supply to the nipple. The excess skin is deepithelialized to preserve the dermal vessels. After mastectomy, the excess skin is imbricated to reduce the skin envelope. The deepithelialized lower flap "autoderm" can be sewn to the pectoralis muscle for coverage of the tissue expander. This technique allows large-breasted and ptotic patients to undergo mastectomy with preservation of their nipple-areolar complex as well as skin reduction to yield an improved cosmetic result. PMID- 26271394 TI - Impact of Timeliness of Resection and Thyroidectomy Margin Status on Survival for Patients with Anaplastic Thyroid Cancer: An Analysis of 335 Cases. AB - BACKGROUND: Controversies regarding anaplastic thyroid cancer (ATC) surround aggressiveness of tumor resection in the presence of extrathyroidal extension and the impact of delayed surgery on patient survival. Our goal was to analyze the survival implications of complete and timely resections. METHODS: Adult patients with ATC were culled from the National Cancer Data Base for the years 2003-2006. Kaplan-Meier curves and Cox proportional hazard regression analyses were used for univariate and multivariate survival analyses, respectively. RESULTS: A total of 680 ATC patients were identified. In the surgical cohort (n = 335), the female-to male ratio was 1.6:1; mean age was 68.6 years. Patients with ATCs were staged as IVA in 42.7 % of cases, IVB in 32.2 %, and IVC in 25.1 %. Median time from diagnosis to surgery was 15 days. Negative margin status was more often achieved in patients diagnosed with stage IVA disease (p < 0.001). Compared to surgical patients, those who did not receive thyroid resections were older and had a more advanced stage of disease (both p < 0.001). In multivariable analyses, positive margin status was associated with increased mortality in stage IVA ATC (p = 0.017) but had no survival impact in stages IVB and IVC (p > 0.05). After adjustment for possible confounders, increasing time from diagnosis to surgery was not found to be associated with compromised survival outcomes for any disease stage. CONCLUSIONS: Timely and aggressive surgical management should be pursued in patients with intrathyroidal disease; however, aggressive resections may not be recommended for patients with stage IVB and IVC disease when morbidity and operative risks outweigh the limited benefits of surgery. PMID- 26271396 TI - TGF Beta1 Expression Correlates with Survival and Tumor Aggressiveness of Prostate Cancer. AB - BACKGROUND: Although biopsy Gleason score and clinical stage can be used to inform treatment decisions for prostate cancer, identifying molecular markers of tumor aggressiveness could lead to a more tailored approaches to therapy. In the present study, we investigated the association of transforming growth factor (TGF)-beta1 levels and various markers of tumor aggressiveness and explore some potential mechanisms underlying the associations. METHODS: We used human and murine prostate cancer cell lines and their respective hormone resistance sub lines, in vitro and in vivo to examine the changes in tumor aggressiveness, as well as the pathway responsible for these changes. Furthermore, 105 prostate cancer biopsy specimens were analyzed to correlate the level of TGF-beta1 with the clinical characteristics of patients. RESULTS: Our data revealed that activated TGF-beta1 signaling resulted in more aggressive tumor growth and augmented the epithelial-mesenchymal transition. Activated IL-6 signaling was associated with TGF-beta1 levels and the aggressive tumor features noted in TGF beta1-positive prostate cancers in vitro and in vivo. Furthermore, the TGF-beta1 levels significantly correlated with Tregs accumulation in vivo. The clinical data indicated that TGF-beta1 immunoreactivity had a moderate positive correlation with IL-6 staining, advanced clinical stage, higher Gleason score, and pretreatment PSA in patients with prostate cancer. CONCLUSIONS: TGF-beta1 levels are significantly associated with aggressive prostate features. In vitro and in vivo alternations of TGF-beta1 expression impacts tumor invasiveness, tumor growth rate and recruitment of immunosuppressive Treg cells in the tumor microenvironment. TGF-beta1 expression may represent a clinical useful biomarker to guide prostate cancer treatment decisions. PMID- 26271395 TI - Pathologic Major Response After FOLFIRINOX is Prognostic for Patients Secondary Resected for Borderline or Locally Advanced Pancreatic Adenocarcinoma: An AGEO FRENCH, Prospective, Multicentric Cohort. AB - PURPOSE: In view of increased response rates and survivals in patients with metastatic pancreatic adenocarcinoma (PAC) with FOLFIRINOX, many centers proposed this regimen as induction chemotherapy for borderline (BR) or locally advanced (LA) PAC. The aim of this study was to assess surgical and oncological outcomes of patients who underwent resection after induction FOLFIRINOX therapy. METHODS: We prospectively identified surgical consecutive BR or LA PAC patients after induction FOLFIRINOX in 20 observational French centers between November 2010 and December 2013. Two independent experts retrospectively evaluated initial CT scan for central review. RESULTS: Eighty patients were included, 47 had BR and 33 had LA PAC. Median number of FOLFIRINOX cycles was 6 (range 1-30) and 65 % of patients received chemoradiation. The 30-day-mortality, major complications, and symptomatic pancreatic fistula rates were 2.5, 22.5, and 4 %, respectively. R0 resection was achieved in 84 %. After a median follow-up of 38.2 months since diagnosis, disease-free survival (DFS) was 17.16 months. The overall survival rates at 12 and 24 months were 92 and 81 %, respectively. A 26 % (n = 21) pathologic major response (pMR) rate was reached. In univariate and multivariate analysis, pMR was a prognostic factor for DFS (hazard ratio 0.33; P = 0.01 and hazard ratio 0.38; P = 0.035). CONCLUSIONS: Resection after induction FOLFIRINOX is safe and associated with similar or better outcomes as upfront surgery in patients with PAC. A pMR was observed in 26 % of cases and was prognostic of DFS. This therapeutic design should be investigated in prospective studies. PMID- 26271397 TI - Defective Mismatch Repair Status was not Associated with DFS and OS in Stage II Colon Cancer Treated with Adjuvant Chemotherapy. AB - BACKGROUND: Mismatch repair (MMR) status has been proposed, with some controversy, as a prognostic and predictive marker in stage II colon cancer. The aim of this study was to evaluate the association between MMR and survival in stage II colon cancer. METHODS: A total of 860 patients with curatively resected stage II colon cancer were selected for inclusion between January 2003 and December 2008. Tumors lacking expression of MLH1 and/or MSH2, as determined by immunohistochemistry, were classified as having deficient MMR (dMMR), whereas other tumors were classified as having proficient MMR (pMMR). Clinical risk (CR) factors were used to divide patients into high or standard CR groups. RESULTS: Of 860 patients, 14.7 % were dMMR, 42.4 % had >=1 CR factors, and 85.8 % patients received adjuvant chemotherapy. MMR status did not affect disease-free survival (DFS; hazard ratio [HR] 1.191, p = 0.415) or overall survival (OS; HR 1.300, p = 0.344). Among CR factors, only pathologic T4 disease tended to associate with poor OS (HR 1.979, p = 0.071). Adjuvant chemotherapy was associated with better DFS (HR 0.393, p < 0.0001) in patients with pMMR tumors. However, in patients with dMMR tumors, adjuvant chemotherapy was not associated with DFS. CONCLUSIONS: MMR status did not affect DFS or OS in patients with stage II colon cancer. In patients treated with adjuvant chemotherapy, dMMR was not associated with DFS and OS. However, adjuvant chemotherapy was associated with improved DFS in pMMR patients. PMID- 26271399 TI - Routine outcome monitoring: An international endeavour. PMID- 26271398 TI - A Practical Approach to the Management of Radiation-Induced Hemorrhagic Cystitis. AB - Radiation-induced hemorrhagic cystitis (HC) is a complication of pelvic radiotherapy, mainly for prostate and uterine cancers. In the acute phase, patients feel urinary urgency and bladder pain. This phase is reversible after radiotherapy. In the chronic stage, an irritative syndrome is coupled with hematuria during the 2-10 years following radiotherapy. Cystoscopy shows white and frosted mucosa with telangiectasia. The incidence is estimated at 5 % or less. It is suggested that the radiation oncologist reviews the dosimetry plan to validate that the lesions coincide with significant radiation exposure confirming diagnosis of radiation-induced HC. The treatment for HC is first symptomatic, with bladder lavage, clot evacuation, coagulation via cystoscopy and blood transfusions if necessary. Subsequently, hyaluronic acid bladder instillation can be done with little toxicity. Hyperbaric oxygen therapy delivers pure oxygen to patients in a pressurized cabin, promoting angio-neogenesis and lowering hypoxia to the irradiated tissues. The clinical response rate is estimated to be around 80 %. Nevertheless, this approach is limited by the low availability, and length of treatment. While surgery remains an effective treatment for HC, it is the last option because of the high morbidity and mortality risks. Prospective studies need to be conducted to identify and evaluate new interventions, particularly for HC. PMID- 26271400 TI - Training of deep microsurgical skill: Establishment of a high-volume intracranial carotid bypass model. AB - OBJECTIVE: To establish a model for a high-volume intracranial carotid bypass operation. METHODS: High-volume internal carotid-middle cerebral artery bypass was performed on 9 cadaver heads with arteries of porcine forearms as grafts by 6 residents with no previous experience in vascular anastomosis on cadavers. The intima was dissected immediately after the anastomoses were completed to observe the patency of anastomosis. RESULTS: After different duration periods of training using this model, 36 vascular anastomoses on 18 sides were successfully performed by the 6 residents with a self-made difficulty regulation device. As the difficulty level increased, the time needed for anastomosis lengthened and patency rate showed a decreasing trend. As the amount of training increased, the residents were able to decrease the amount of time to complete the operation with increasing patency rates. CONCLUSIONS: The model of high-volume internal carotid middle cerebral artery bypass with arteries of porcine forearms has the advantages of material similarity, easy access of grafts, better simulation of intraoperative conditions, and adjustable difficulties. Our results suggest that this new procedure has a better simulation-training platform which is closer to the real surgical procedure for surgeons willing to master the technique of a high-volume bypass operation. PMID- 26271402 TI - Sex differences in lower extremity stiffness and kinematics alterations during double-legged drop landings with changes in drop height. AB - The aim of this study was to determine whether sex differences and effect of drop heights exist in stiffness alteration of the lower extremity during a landing task with a drop height increment. Twelve male participants and twelve female participants performed drop landings at two drop heights (DL40 and DL60; in cm). The leg and joint stiffnesses were calculated using a spring-mass model, and the joint angular kinematics were calculated using motion capture. Ground reaction forces (GRFs) were recorded using a force plate. The peak vertical GRF of the females was significantly increased when the drop height was raised from 40 to 60 cm. Significantly less leg and knee stiffness was observed for DL60 in females. The ankle, knee, and hip angular displacement during landing were significantly increased with drop height increment in both sexes. The knee and hip flexion angular velocities at contact were significantly greater for the 60 cm drop height relative to the 40 cm drop height in males. These sex disparities regarding the lower extremity stiffness and kinematics alterations during drop landing with a drop height increment would predispose females to lower extremity injury. PMID- 26271401 TI - Olfaction preservation after removal of large tuberculum sellae meningiomas via a superior interhemispheric approach. A quantitative and qualitative study. AB - INTRODUCTION: We present a prospective series of tuberculum sellae meningioma (TSM) resected via a superior interhemispheric (IH) approach in 10 patients who preoperatively and postoperatively underwent extensive olfaction testing using a standardised test battery. PATIENTS AND METHODS: This prospective longitudinal study evaluated the olfactory function after TSM resection. The resection was performed via a superior interhemispheric (IH) approach. The quantitative and qualitative analyses of the olfactory function were assessed with the Biolfa((r)) olfactory test (at 6 months). RESULTS: Between November 2009 and April 2012, 10 consecutive patients with symptomatic TSM and preserved olfactory function were operated via a superior IH approach. For the self-evaluation criteria of the olfactory function, the mean preoperative visual analog scale score was 8.8. The mean preoperative total quantitative (/27) scored 18.2 +/- 6.3 for this cohort of 10 patients. In the postoperative period, the mean total score decreased non significantly to 15.8 +/- 8.8 (Wilcoxon test, P = 0.085). The mean preoperative qualitative score (/8) was 5.5 +/- 1.7 and in the postoperative period decreased, non-significantly, to 4.7 +/- 2.6 (Wilcoxon test, P = 0.12). The olfactory function was quantitatively and qualitatively preserved in 6 patients (60%), but a postoperative deterioration occurred in 2 (20%) and an anosmia in 2 (20%). Size and invasive characteristics of the meningioma determined the post-surgical deterioration. CONCLUSION: Olfaction is an important factor of emotional and social life, which needs to be integrated into the challenge regarding the resection of TSM. The risks of nerve damage are reviewed. PMID- 26271403 TI - Bioinformatics tools for lncRNA research. AB - Current experimental methods to identify the functions of a large number of the candidates of long non-coding RNAs (lncRNAs) are limited in their throughput. Therefore, it is essential to know which tools are effective for understanding lncRNAs so that reasonable speed and accuracy can be achieved. In this paper, we review the currently available bioinformatics tools and databases that are useful for finding non-coding RNAs and analyzing their structures, conservation, interactions, co-expressions and localization. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa. PMID- 26271404 TI - Emerging challenges in implementing universal health coverage in Asia. AB - As countries in Asia converge on the goal of universal health coverage (UHC), some common challenges are emerging. One is how to ensure coverage of the informal sector so as to make UHC truly universal; a second is how to design a benefit package that is responsive and appropriate to current health challenges, yet fiscally sustainable; and a third is how to ensure "supply-side readiness", i.e. the availability and quality of services, which is a necessary condition for translating coverage into improvements in health outcomes. Using examples from the Asia region, this paper discusses these three challenges and how they are being addressed. On the first challenge, two promising approaches emerge: using general revenues to fully cover the informal sector, or employing a combination of tax subsidies, non-financial incentives and contributory requirements. The former can produce fast results, but places pressure on government budgets and may induce informality, while the latter will require a strong administrative mandate and systems to track the ability-to-pay. With respect to benefit packages, we find considerable variation in the nature and rigor of processes underlying the selection and updating of the services included. Also, in general, packages do not yet focus sufficiently on non-communicable diseases (NCDs) and related preventive outpatient care. Finally, there are large variations and inequities in the supply-side readiness, in terms of availability of infrastructure, equipment, essential drugs and staffing, to deliver on the promises of UHC. Health worker competencies are also a constraint. While the UHC challenges are common, experience in overcoming these challenges is varied and many of the successes appear to be highly context-specific. This implies that researchers and policymakers need to rigorously, and regularly, assess different approaches, and share these findings across countries in Asia - and across the world. PMID- 26271407 TI - Raising the standard for clinical care of patients with Ebola virus disease. PMID- 26271406 TI - Clinical presentation, biochemical, and haematological parameters and their association with outcome in patients with Ebola virus disease: an observational cohort study. AB - BACKGROUND: Clinical management of Ebola virus disease remains challenging. Routine laboratory analytics are often unavailable in the outbreak setting, and few data exist for the associated haematological and biochemical abnormalities. We aimed to assess laboratory and clinical data from patients with Ebola virus disease to better inform clinical management algorithms, improve understanding of key variables associated with outcome, and provide insight into the pathophysiology of Ebola virus disease. METHODS: We recruited all patients, alive on arrival, with confirmed Ebola virus disease who were admitted to the Kerry Town Ebola treatment centre in Sierra Leone. At admission, all patients had clinical presentation recorded and blood taken for Ebola confirmation using reverse-transcriptase-PCR (RT-PCR) and for haematological and biochemical analysis. We studied the association between these and clinical outcome. The primary outcome was discharge from the Ebola treatment centre. FINDINGS: 150 patients were admitted to the treatment centre between Dec 8, 2014, and Jan 9, 2015. The mean age of patients was 26 years (SD 14.7). Case fatality rate was 37% (55/150). Most patients presented with stage 2 (gastrointestinal involvement, 72/118 [61%]) and stage 3 (severe or complicated, 12/118 [10%]) disease. Acute kidney injury was common (52/104 [50%]), as were abnormal serum potassium (32/97 [33%]), severe hepatitis (54/92 [59%]), and raised C-reactive protein (21/100 [21%]). Haematological abnormalities were common, including raised haematocrit (15/100 [15%]), thrombocytopenia (47/104 [45%]), and granulocytosis (44/104 [42%]). Severe acute kidney injury, low RT-PCR cycle threshold (<20 cycles), and severe hepatitis were independently associated with mortality. INTERPRETATION: Ebola virus disease is associated with a high prevalence of haematological and biochemical abnormalities, even in mild disease and in the absence of gastrointestinal symptoms. Clinical care that targets hypovolaemia, electrolyte disturbance, and acute kidney injury is likely to reduce historically high case fatality rates. FUNDING: None. PMID- 26271408 TI - Using association rule mining to identify risk factors for early childhood caries. AB - BACKGROUND AND OBJECTIVE: Early childhood caries (ECC) is a potentially severe disease affecting children all over the world. The available findings are mostly based on a logistic regression model, but data mining, in particular association rule mining, could be used to extract more information from the same data set. METHODS: ECC data was collected in a cross-sectional analytical study of the 10% sample of preschool children in the South Backa area (Vojvodina, Serbia). Association rules were extracted from the data by association rule mining. Risk factors were extracted from the highly ranked association rules. RESULTS: Discovered dominant risk factors include male gender, frequent breastfeeding (with other risk factors), high birth order, language, and low body weight at birth. Low health awareness of parents was significantly associated to ECC only in male children. CONCLUSIONS: The discovered risk factors are mostly confirmed by the literature, which corroborates the value of the methods. PMID- 26271409 TI - [Acute myelopathy: importance of early diagnosis]. PMID- 26271410 TI - [Teledermatology in Paediatrics. Observations in daily clinical practice]. AB - INTRODUCTION: Teledermatology is a technique that is increasingly being developed. There are many studies that assess this discipline in the general population, but few studies analyse the paediatric population exclusively. The aims of this study are to describe the distribution of diseases consulted through teledermatology, the use of this technique to avoid face-to-face consultations, and the agreement between virtual and face-to-face diagnoses, in the paediatric population. MATERIAL AND METHODS: The work consisted of an observational and retrospective study of the virtual consultations made between May 2011 and January 2015 through a store-and-forward teledermatology programme, involving patients from 0 to 15 years. We collected demographic data, as well as the diagnoses made by the paediatrician who made the virtual consultation, and by the dermatologists who assessed the virtual and the face-to-face consultations, the indication given by the dermatologist who assessed the virtual consultation (discharge or referral), reason for referral, and diagnostic agreement rate. RESULTS: A total of 183 virtual consultations were analysed. The most frequent diagnoses were inflammatory diseases (39%), benign pigmented lesions (23%), and infectious diseases (20%). Almost half of the virtual consultations (48%) were referred for a face-to-face diagnosis. Diagnostic agreement between the dermatologist who evaluated the virtual consultation and the dermatologist who evaluated the face-to-face consultation was 89%, and 66% between the paediatrician who made the virtual consultation and the dermatologist who assessed it. CONCLUSIONS: Virtual consultations have a similar disease distribution to conventional (face-to-face) referrals. Approximately half of the virtual consultations do not require a subsequent face-to-face visit. The agreement rate between the diagnoses given by both dermatologists (virtual and face-to-face diagnoses) is high. PMID- 26271412 TI - Comparison of TP53 mutations screening by functional assay of separated allele in yeast and next-generation sequencing in myelodysplastic syndromes. AB - TP53 mutations are major prognostic factors in many hematological malignancies including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Next generation sequencing (NGS) has improved the detection of such mutations by identifying small mutated clones but functional method like FASAY (functional assay of separated allele in yeast) may prove interesting. We compared the detection of TP53 mutations by FASAY and NGS in 91 patients with AML or MDS. By FASAY, 91% of assays were evaluable and 47 patients (57%) had a functional and 36 (43%) a non-functional p53 protein. FASAY could not conclude in 8 cases (9%), mainly because of poor RNA quality. No TP53 mutation was found using NGS in 50 cases (55%), and at least one mutation was detected in 41 cases (45%). The p53 status was concordant between FASAY and NGS in 95% (79/83) of cases. The four discordances included mutations detected by FASAY only in two cases, and by NGS only in two cases. Mutations not detected by NGS consisted of insertions in intronic regions, which were not analyzed by this assay. Mutations not detected by FASAY were mutations for which the percentage of mutated allele was less than 10%, including one mutation reported as non-deleterious in the IARC database. Overall, our data suggest that FASAY is an effective and reliable method to detect TP53 mutations in AML and MDS, which allows the assessment of the protein functionality, contrary to a sequencing approach. PMID- 26271411 TI - Metabolic syndrome and risk of major coronary events among the urban diabetic patients: North Indian Diabetes and Cardiovascular Disease Study-NIDCVD-2. AB - OBJECTIVE: The present study aimed at estimating the prevalence of metabolic syndrome (MetS) and prospectively, evaluating cardiovascular events among Asian Indians type 2 diabetic subjects. METHODS: The sample comprised 1522 type 2 diabetic mellitus (T2DM) subjects aged 25-91years, who participated in the North Indian Diabetes and Cardiovascular Disease Study (NIDCVD). The participants were screened for hypertension, dyslipidemia, obesity and cardiovascular events. Anthropometric, clinical and biochemical measurements were done in all subjects. The prevalence of MetS was estimated in all the subjects according to the harmonized criteria of 2009. RESULTS: The prevalence of MetS among urban Indian diabetic subjects was 71.9% and was significantly higher in females (86%) as compared to males (57.9%). To determine the independent predictors of the MetS in diabetic sample, binary logistic regression analyses were performed using demographic and biochemical parameters. Significant differences in the indices of generalized and abdominal obesity and lipids (total cholesterol, high density lipoprotein) were observed (p<0.01) in male:female and MetS and non-MetS comparisons. Regression analysis for prediction of CAD showed that family history, age, body mass index (BMI), SBP, physical inactivity and hypertension independently and significantly predicted the disease outcome. Binary logistic regression analysis revealed that MetS may be an independent risk/predictor of CAD (odd ratio (OR)=3.44, CI 1.31-9.01, p=0.012) along with higher age groups, BMI and hypertension in Indian population. CONCLUSION: The study demonstrated that the high prevalence of MetS and its different components were positively associated with a higher risk of CAD in north Indian diabetic subjects. Nevertheless, MetS is a major health problem in India, comprehensive population studies are warranted for estimation of incidence and prevalence, and education should be provided on its prevention and control to reduce the diabetes-related morbidity and mortality. PMID- 26271413 TI - Toxicity of doxorubicin-transferrin conjugate is connected to the modulation of Wnt/beta-catenin pathway in human leukemia cells. AB - Chronic myeloid leukemia (CML) is a disorder of hematopoietic stem cells caused by constitutive activation of the BCR/ABL tyrosine kinase. However, the tyrosine kinase inhibitors like imatinib mesylate are not effective in the patients with advanced-stage of CML. Hence, there is an urgent need for new approaches to overcome a cancer cell's resistance in CML long term therapy. Development of new drug carriers, is presently one of the most challenging tasks in experimental oncology. In this report we investigated whether the toxicity of newly synthetized doxorubicin transferrin conjugate (DOX-TRF) may be connected to the limitation of multidrug resistance in CML cells by the alternations of Wnt/beta catenin signaling pathway. The studies were performed on human chronic myeloid leukemia cell lines sensitive (K562) and resistant (K562/DOX) to doxorubicin. Our research proves that DOX-TRF conjugate displays higher cytotoxicity toward both examined cell lines than the reference free drug (DOX) and induces more extensive pro-apoptotic changes. Moreover, by the of engagement of Wnt pathway agonist (LiCl) and antagonist (ICG 001) we demonstrate that DOX-TRF conjugate effectively reduces transcription of key genes involved in beta-catenin signaling transduction trial (Wnt3a, DVL-1, FZD-3, LRP5, beta-catenin, DKK2) and triggers morphology alternations of CML cells. PMID- 26271414 TI - The importance of analysis of long-range rearrangement of BRCA1 and BRCA2 in genetic diagnosis of familial breast cancer. AB - Germline BRCA gene mutations are reportedly associated with hereditary breast and ovarian cancers. Identification of BRCA mutations greatly improves the preventive strategies and management of breast cancer. Sanger sequencing has been the gold standard in identifying these mutations. However, 4-28% of inherited BRCA mutations may be due to large genomic rearrangements (LGRs), which could be missed by using Sanger sequencing alone. Our aim is to evaluate the pick-up rate of LGRs in our cohort. A total of 1,236 clinically high-risk patients with breast and/or ovarian cancers were recruited through The Hong Kong Hereditary Breast Cancer Family Registry from 2007 to 2014. Full gene sequencing (either Sanger or next generation sequencing) and multiplex ligation-dependent probe amplification (MLPA) were performed. We identified 120 deleterious BRCA mutations: 57 (4.61%) were in BRCA1 and 63 (5.10%) were in BRCA2. LGRs accounted for 6.67% (8 of 120) of all BRCA mutations, whereas 8.77 % (5 of 57) were BRCA1 mutations and 4.76% (3 of 63) were BRCA2 mutations. Through this integrated approach, both small nucleotide variations and LGRs could be detected. We suggest that MLPA should be incorporated into the standard practice for genetic testing to avoid false negative results, which would greatly affect the management of these high-risk families. PMID- 26271415 TI - Comparative transcriptome analysis reveals that the extracellular matrix receptor interaction contributes to the venous metastases of hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is the most common type of liver cancer in the world. Portal vein tumor thrombus (PVTT) is one of the most serious complications of HCC and is strongly correlated with a poor prognosis for HCC patients. However, the detailed mechanism of PVTT development remains to be explored. In this study, we present a large-scale transcriptome analysis, by RNA sequencing, of 11 patients diagnosed with HCC with PVTT. The dysregulated genes between HCC and PVTT suggested that the extracellular matrix receptor interaction was correlated with the venous metastases of HCC. Among all of the recurrent alternative splicing events, we identified exon 6 skipping of RPS24, which is likely to be a cancer driver. We also identified five common fusion genes between HCC and its corresponding PVTT samples, including ARID1A-GPATCH3, MDM1-NUP107, PTGES3-RARG, PRLR-TERT, and C9orf3-TMC1. All of these findings broaden our knowledge of PVTT development and may also contribute to the diagnosis and treatment of HCC patients with PVTT. PMID- 26271417 TI - [Surgical risks and their prevention in laparoscopic cholecystectomy]. AB - It was analyzed the treatment results of 3739 patients with chronic and acute cholecystitis who underwent laparoscopic cholecystectomy. Three groups of predisposing factors were determined in 427 high risk patients. Laparoscopic cholecystectomy in view of these factors and enhancement of approach to dissect gall-bladder decreases the number of intraoperative complications. PMID- 26271418 TI - [Estimation of the role of octreotide in treatment of severe pancreatic necrosis]. AB - It was analyzed the results of treatment of 204 patients with severe course of destructive pancreatitis (severity of organs' dysfunction was 9 and more scores according to APACHE-II scale upon admission to the hospital). Logistic regression and Cox regression were used along with univariant statistical analysis, what permitted to estimate overall effect of octreotide and other potential predictors including severity of condition and medical factors on the mortality rate and extension of necrosis in patients with pancreatic necrosis. It was established that the use of octreotide in case of severe pancreatic necrosis significantly decreases mortality and extension of necrosis. PMID- 26271416 TI - [Cerebral dysfunction as a component of multiple organ failure in surgical patients (lecture)]. AB - Development of delirium in critically ill patients is considered complication of basic disease which increases patients' hospital stay, mortality rate and the cost of treatment. Despite wide prevalence delirium often remains undiagnosed by physicians in ICU. Routine use of screening scales permits to diagnose delirium timely. Multicomponent preventive strategy with intermittent sedation and dexmedetomidine improves the results of treatment. PMID- 26271419 TI - [Choice of surgical treatment in patients with acute destructive pancreatitis]. AB - Medical and diagnostic algorithm in patients with pancreatic necrosis is developed. It takes into consideration features and expansion of necrotic process in retroperitoneal space, objective severity of patients' condition according to SAPS scale and inflammatory process according to serum procalcitonin concentration. Comparative analysis revealed that the use of developed algorithm improves results of treatment. PMID- 26271420 TI - [State of immune and cytokine status in acute ulcerative gastroduodenal bleeding]. AB - The paper analyzes the results of a survey of 37 patients with acute ulcerative gastroduodenal hemorrhage. During endoscopy found that 7 patients the cause of bleeding was gastric ulcer, duodenal ulcer in 27 and 3 concomitant ulcer. Hemostasis was evaluated by J. Forrest and the severity of blood loss was assessed by the A.A. Shalimov: with blood loss was mild in 11 patients, the average degree--12 and with severe--14. In all patients on admission in the peripheral blood were studied state of cellular, humoral and cytokine profile: CD3+, CD4+, CD8+, CD4+/CD8 + and CD19+, FI, FF, CEC, IgA, M, G, TNF-alpha, IFN gamma, IL-1, IL-2, IL-4, IL-6, IL-8 and IL-10. In general patients with on admission revealed significant changes in the immune and cytokine status. In cellular immunity occurs immunosuppression. Disturbances in humoral immunity manifests itself in increased levels of lymphocytes in blood loss and hardships of all multi-directional changes in the concentration of immunoglobulins depending on the amount of blood loss. When there is an imbalance in cytokine status, the depth of which depends on the degree of blood loss. PMID- 26271421 TI - [Prevalence of erosive esophagitis and peptic esophageal strictures]. AB - Gastroesophageal reflux disease is a widespread among population in economically developed countries including Russia. It was analyzed the results of 34 903 endoscopic examinations of upper gastrointestinal tract in ethnically and socially homogeneous population of Leningrad region with symptoms of gastric dispepsia. Procedures were performed for the period 2007-2013. Prevalence of erosive esophagitis was 4.9%. Peptic esophageal strictures due to chronic reflux associated inflammation were revealed in 0.2% of examined patients (3.7% of patients with erosive esophagitis). Obtained data allow to considergastroesophageal reflux disease as a socially significant problem in Russia requiring close attention and further study. PMID- 26271422 TI - [Endoprosthetic replacement with lifting of abdominal wall in treatment of umbilical and postoperative ventral hernias]. AB - The results of complex clinical and ultrasonic investigation of abdominal wall and following surgical treatment in 60 women with umbilical and postoperative large ventral hernias combined with abdomen ptosis were analyzed. Patients were divided into 2 groups with 30 people per group. Endoprosthetic replacement of abdominal wall defect using standard polypropylene prosthesis was applied in the 1st group, endoprosthetic replacement with musculoaponeurotic tissues lifting in hypogastric area using original super lightweight polypropylenepolyvinylidenefluoride prosthesis--in the 2nd group. Polypropylene endoprosthesisconsist of main flap 15*15 cm with roundish edges and additional flap 5*40 cm in the form of wide stripe placed at the lower edge of main flap transversely to its direction. It was revealed increased physical health component in 1.8 times, psychic--in 2.5 times in the 2nd group. Thus number of excellent results increased on 33.3% and amount of satisfactory outcomes reduced on 30%. PMID- 26271423 TI - [Infectious complications after kindred kidney allotransplantation]. AB - It was analyzed the medical records of 231 patients who underwent living kindred donor kidney transplantation. Early postoperative complications were observed in 51 (22%) patients including infectious events in 30 cases namely pyelonephritis (13), pneumonia (6), sepsis (5), wound infection (3), pulmonary tuberculosis (2) and esophageal mycosis (1). Microflora investigation revealed predominantly gram negative bacteria including enterobacteriaceae (K. pneumoniae, E. coli and E. cloacae) and nonfermentable bacteria (P. aeruginosa, Acinetobacter spp.). Analysis of 7-year antibiotic susceptibility showed that polymyxin, imipenem, cefoperazone/sulbactam and amikacin preserve their activity against enterobacteriaceae and pseudomonas; linezolid, vancomycinum and moxifloxacin- against staphylococcus; voriconazole, amphotericinum B and fluconazole--against Candida spp. These medicines are preferred for antibiotic prevention of perioperative and early postoperative infectious complications. PMID- 26271424 TI - [Efficiency of minimally invasive methods in treatment of varicose veins]. AB - It was analyzed the results of studies comparing an efficiency of minimally invasive methods in treatment of varicose veins of lower extremities. Based on presented data similar efficiency of minimally invasive methods and conventional surgical treatment was proved. The graph reflecting remote results was made. PMID- 26271426 TI - [Clinical-economic features of different hemostasis strategies in advanced liver resection]. PMID- 26271425 TI - [Features of lower extremities deep veins recanalization in patients with thrombosis by using of sulodexide]. PMID- 26271427 TI - [Simultaneous surgery in patient with common iliac artery false aneurysm and pancreatic cancer]. PMID- 26271428 TI - [Laparoscopic ileocecal resection for cecalangiodysplasia]. PMID- 26271429 TI - [Method of pancreatojejunostomy in case of pancreatic head subtotal resection]. PMID- 26271430 TI - [Surgical treatment of recurrent echinococcosis]. PMID- 26271431 TI - [Dangerous foreign matter of esophagus and stomach]. PMID- 26271432 TI - Tea and Parkinson's disease: Constituents of tea synergize with antiparkinsonian drugs to provide better therapeutic benefits. AB - The major neurodegenerative movement disorder Parkinson's disease (PD) is characterized by rest-tremor, akinesia, rigidity and inability to initiate movements. PD syndromes result from excessive loss of dopamine from the forebrain striatal region, due to dopaminergic neuronal death in the midbrain substantia nigra pars compacta. PD with multifactorial etiology is believed to ideally require a drug or different drugs that act(s) at multiple sites of action for symptomatic relief. Replenishing striatal dopamine by providing L-3,4 dihydroxyphenylalanine (l-DOPA) along with a peripheral aromatic amino acid decarboxylase inhibitor is the mainstay treatment for PD. Such prolonged therapy leads to debilitating effects, often worsening the affection. Interestingly some under-appreciated pharmaceutical compounds, including constituents of plants and nutraceuticals can synergize with l-DOPA to support mitochondrial function, suppress inflammation, ease oxidative stress, and in turn slow the progression of the disease. Tea and other dietary polyphenols are shown to provide relief to the disease syndromes and provide neuroprotection in cellular and animal models of PD. At par with these findings, random epidemiological studies in certain populations of the world support habitual tea drinking to reduce the risk of PD. The present review addresses how these tea constituents work at the cellular level to render effective control of the disease syndromes and suggests that tea synergizes with established drugs, such as l-DOPA to maximize their effects at certain levels in the disease phenotype-inducing canonical pathways of PD. PMID- 26271434 TI - Diabetes-related emotional distress instruments: a systematic review of measurement properties. AB - OBJECTIVES: The objectives of this study were to identify all available diabetes related emotional distress instruments and evaluate the evidence regarding their measurement properties to help in the selection of the most appropriate instrument for use in practice and research. DESIGN: A systematic literature search was performed. DATA SOURCES: PubMed, Embase, CINAHL, and PsycINFO were searched systematically for articles on diabetes-related emotional distress instruments. REVIEW METHODS: The Consensus-based Standards for the Selection of Health Measurement Instruments checklist was used to evaluate the methodological quality of the identified studies. The quality of results with respect to the measurement properties of each study was evaluated using Terwee's quality criteria. An ancillary meta-analysis was performed. RESULTS: Of the 2345 articles yielded by the search, 19 full-text articles evaluating 6 diabetes-related emotional distress instruments were included in this study. No instrument demonstrated evidence for all measurement properties. The Problem Areas in Diabetes scale (PAID) was the most frequently studied and the best validated of the instruments. Pooled summary estimates of the correlation coefficient between the PAID and serum glycated hemoglobin revealed a positive but weak correlation. CONCLUSIONS: No diabetes-related emotional distress instrument demonstrated evidence for all measurement properties. No instrument was better than another, although the PAID was the best validated and is thus recommended for use. Further psychometric studies of the diabetes-related emotional distress instruments with rigorous methodologies are required. PMID- 26271433 TI - Cell and brain tissue imaging of the flavonoid fisetin using label-free two photon microscopy. AB - Over the last few years, we have identified an orally active, novel neuroprotective and cognition-enhancing molecule, the flavonoid fisetin. Fisetin not only has direct antioxidant activity but it can also increase the intracellular levels of glutathione, the major intracellular antioxidant. Fisetin can also activate key neurotrophic factor signaling pathways. In addition, it has anti-inflammatory activity against microglia and astrocytes and inhibits the activity of lipoxygenases, thereby reducing the production of pro-inflammatory eicosanoids and their by-products. However, key questions about its targets and brain penetration remain. In this study, we used label-free two-photon microscopy of intrinsic fisetin fluorescence to examine the localization of fisetin in living nerve cells and the brains of living mice. In cells, fisetin but not structurally related flavonols with different numbers of hydroxyl groups, localized to the nucleoli suggesting that key targets of fisetin may reside in this organelle. In the mouse brain, following intraperitoneal injection and oral administration, fisetin rapidly distributed to the blood vessels of the brain followed by a slower dispersion into the brain parenchyma. Thus, these results provide further support for the effects of fisetin on brain function. In addition, they suggest that label-free two-photon microscopy may prove useful for studying the intracellular and tissue distribution of other intrinsically fluorescent flavonoids. PMID- 26271435 TI - Effect of lignin on water vapor barrier, mechanical, and structural properties of agar/lignin composite films. AB - Biodegradable composite films were prepared using two renewable resources based biopolymers, agar and lignin alkali. The lignin was used as a reinforcing material and agar as a biopolymer matrix. The effect of lignin concentration (1, 3, 5, and 10wt%) on the performance of the composite films was studied. In addition, the mechanical, water vapor barrier, UV light barrier properties, FE SEM, and TGA of the films were analyzed. The agar/lignin films exhibited higher mechanical and UV barrier properties along with lower water vapor permeability compared to the neat agar film. The FTIR and SEM results showed the compatibility of lignin with agar polymer. The swelling ratio and moisture content of agar/lignin composite films were decreased with increase in lignin content. The thermostability and char content of agar/lignin composite films increased with increased lignin content. The results suggested that agar/lignin films have a potential to be used as a UV barrier food packaging material for maintaining food safety and extending the shelf-life of the packaged food. PMID- 26271436 TI - Validation of a commercially available enzyme-linked immunoabsorbent assay for the quantification of human alpha-Synuclein in cerebrospinal fluid. AB - The quantification of alpha-Synuclein in cerebrospinal fluid (CSF) as a biomarker has gained tremendous interest in the last years. Several commercially available immunoassays are emerging. We here describe the full validation of one commercially available ELISA assay for the quantification of alpha-Synuclein in human CSF (Covance alpha-Synuclein ELISA kit). The study was conducted within the BIOMARKAPD project in the European initiative Joint Program for Neurodegenerative Diseases (JPND). We investigated the effect of several pre-analytical and analytical confounders: i.e. (1) need for centrifugation of freshly drawn CSF, (2) sample stability, (3) delay of freezing, (4) volume of storage aliquots, (5) freeze/thaw cycles, (6) thawing conditions, (7) dilution linearity, (8) parallelism, (9) spike recovery, and (10) precision. None of these confounders influenced the levels of alpha-Synuclein in CSF significantly. We found a very high intra-assay precision. The inter-assay precision was lower than expected due to different performances of kit lots used. Overall the validated immunoassay is useful for the quantification of alpha-Synuclein in human CSF. PMID- 26271438 TI - Reply: To PMID 25887629. PMID- 26271437 TI - Fast conversion of scFv to Fab antibodies using type IIs restriction enzymes. AB - Single chain variable fragment (scFv) antibody libraries are widely used for developing novel bioaffinity reagents, although Fab or IgG molecules are the preferred antibody formats in many final applications. Therefore, rapid conversion methods for combining multiple DNA fragments are needed to attach constant domains to the scFv derived variable domains. In this study we describe a fast and easy cloning method for the conversion of single framework scFv fragments to Fab fragments using type IIS restriction enzymes. All cloning steps excluding plating of the Fab transformants can be done in 96 well plates and the procedure can be completed in one working day. The concept was tested by converting 69 scFv clones into Fab format on 96 well plates, which resulted in 93% success rate. The method is particularly useful as a high-throughput tool for the conversion of the chosen scFv clones into Fab molecules in order to analyze them as early as possible, as the conversion can significantly affect the binding properties of the chosen clones. PMID- 26271439 TI - Rapid start-up and microbial characteristics of partial nitrification granular sludge treating domestic sewage at room temperature. AB - The successful suppression of nitrite-oxidizing bacteria in the partial nitrification (PN) stage was the main challenge for the application of autotrophic nitrogen removal process treating mainstream sewage. In this study, two identical PN granular reactors (P1 and P2) were rapid started-up using the simultaneous PN and granulation strategy, for treating the domestic sewage. P1 was seeded with 30% PN granular sludge to induce nucleation, in which the granule size achieved to more than 400MUm in 12d, with ammonia oxidation rate and nitrite accumulation rate of 80% and 95%, respectively, while P2 realized granulation in 42d. The presence of organic matters and specific structure of granules were profitable for the stability of PN for treating sewage with low ammonia. High throughput pyrosequencing results indicated the biodiversity of both reactors decreased after start-up, and Nitrosomonas was the predominant specie of aerobic ammonia-oxidizing bacteria in PN granular sludge. PMID- 26271440 TI - Exploring biochemical and functional features of Leishmania major phosphoenolpyruvate carboxykinase. AB - This work reports the first functional characterization of leishmanial PEPCK. The recombinant Leishmania major enzyme (Lmj_PEPCK) exhibits equivalent kcat values for the phosphoenolpyruvate (PEP) and oxaloacetate (OAA) forming reactions. The apparent Km towards OAA is 10-fold lower than that for PEP, while the Km values for ADP and ATP are equivalent. Mutagenesis studies showed that D241, D242 and H205 of Lmj_PEPCK like the homologous residues of all known PEPCKs are implicated in metal ions binding. In contrast, the replacement of R43 for Q nearly abolishes Lmj_PEPCK activity. Moreover, the Y180F variant exhibits unchanged Km values for PEP, Mn(2+), and [Formula: see text] , being the kcat for PEP- but not that for OAA-forming reaction more notably decreased. Instead, the Y180A mutant displays an increase in the Km value towards Mn(2+). Therefore in Lmj_PEPCK, Y180 seems to exert different functions to those of the analogous residue in ATP- and GTP dependant enzymes. Besides, the guanidinium group of R43 appears to play an essential but yet unknown role. These findings promote the need for further structural studies to disclose whether Y180 and R43 participate in the catalytic mechanism or/and in the transitions between the open and the catalytically competent (closed) forms of Lmj_PEPCK. PMID- 26271441 TI - Rate-limiting steps of a stereochemistry retaining beta-d-xylosidase from Geobacillus stearothermophilus acting on four substrates. AB - Kinetic experiments of GSXynB2, a GH52 retaining beta-xylosidase, acting on 2 nitrophenyl-beta-d-xylopyranoside (2NPX), 4-nitrophenyl-beta-d-xylopyranoside (4NPX), 4-methylumbelliferyl-beta-d-xylopyranoside (MuX) and xylobiose (X2) were conducted at pH 7.0 and 25 degrees C. Catalysis proceeds in two steps (xylodidation followed by dexylosidation): E + substrate TO E-xylose + leaving group TO E + xylose. kcat falls into two groups: 4NPX (1.95 s(-1)) and 2NPX, MuX and X2 (15.8 s(-1), 12.6 s(-1), 12.8 s(-1), respectively). Dexylosylation (E xylose to E + xylose), the common step for the enzymatic hydrolysis of the four substrates, must exceed 15.8 s(-1). kcat of 4NPX would seem mainly limited by xylosylation (step 1) and the other three substrates would seem mainly limited by dexylosylation (step 2) - a conclusion that critically lacks chemical justification (compare 4NPX and 2NPX). Presteady-state rates indicate rapid xylosidation rates for all substrates so a later step (not dexylosidation) is rate-limiting for 4NPX. That 2NPX is an onlier and 4NPX is an outlier (both leaving group pKa of 7.2) of the Bronsted plot pattern (logkcat vs pKa of phenol leaving group) is thus possibly explained by 4NP release. The pH dependency of kcat 2NPX encompasses 2 bell-shaped curves with peaks of pH 3 and pH 7. PMID- 26271442 TI - Type 2 diabetes is associated with postprandial amino acid measures. AB - Most studies examining the association between type 2 diabetes (T2D) and amino acids have focused on fasting concentrations. We hypothesized that, besides fasting concentrations, amino acid responses to a standardized meal challenge are also associated with T2D. In a cross-sectional study of 525 participants (165 newly-diagnosed T2D, 186 newly-diagnosed impaired fasting glycaemia, and 174 normal fasting glucose), we examined postprandial amino acid concentrations and the responses (defined as the concentrations and responses 150 min after a standardized meal) of fourteen amino acids in relation to T2D. T2D was associated with lower postprandial concentration of seven amino acids compared to the normal fasting glucose group (lowest effect estimate for serine: -0.54 standard deviations (SD) (95% CI: -0.77, -0.32)), and higher concentrations of phenylalanine, tryptophan, tyrosine and (iso-)leucine (highest effect estimate for (iso-)leucine: 0.44 SD (95% CI: 0.20, 0.67)). Regarding the meal responses, T2D was associated with lower responses of seven amino acids (ranging from -0.55 SD ((95% CI): -0.78, -0.33) for serine to -0.25 SD ((95% CI: -0.45, -0.02) for ornithine). We conclude that T2D is associated with postprandial concentrations of amino acids and a reduced amino acid meal response, indicating that these measures may also be potential markers of T2D. PMID- 26271443 TI - 4-O-methylascochlorin suppresses differentiation of 3T3-L1 preadipocytes by inhibiting PPARgamma expression through regulation of AMPK/mTOR signaling pathways. AB - Obesity increases the risk of developing many chronic diseases, including type 2 diabetes and certain cancers, and is thereby associated with premature death. The present study was conducted to identify the inhibitory effect of the ascochlorin derivative 4-O-methylascochlorin (MAC) on the differentiation of 3T3-L1 preadipocytes. MAC suppressed the differentiation of 3T3-L1 preadipocytes and inhibited the expression of adipocyte differentiation marker genes, FABP4, PPARgamma and C/EBPalpha. In addition, we found that the inhibitory effects of MAC on differentiation of 3T3-L1 preadipocytes were caused by suppression of mTORC1 via inhibition of mTOR/p70S6K/4E-BP1 phosphorylation and activation of Raptor phosphorylation. MAC also regulated the PPARgamma expression and the mTORC1 activation by increasing AMPK phosphorylation and inhibiting PI3K/Akt, which suggest that MAC suppresses the differentiation of 3T3-L1 adipocytes by regulating the AMPK- and PI3K-mTOR-PPARgamma signaling pathways. Furthermore, animal model results showed that the phosphorylation of AMPK was enhanced in the liver of C57BL/6 mice intraperitoneally injected with MAC. These results indicate that MAC could be a therapeutic agent for obesity involving PPARgamma and AMPK. PMID- 26271444 TI - Open challenges in structure-based virtual screening: Receptor modeling, target flexibility consideration and active site water molecules description. AB - Structure-based virtual screening is currently an established tool in drug lead discovery projects. Although in the last years the field saw an impressive progress in terms of algorithm development, computational performance, and retrospective and prospective applications in ligand identification, there are still long-standing challenges where further improvement is needed. In this review, we consider the conceptual frame, state-of-the-art and recent developments of three critical "structural" issues in structure-based drug lead discovery: the use of homology modeling to accurately model the binding site when no experimental structures are available, the necessity of accounting for the dynamics of intrinsically flexible systems as proteins, and the importance of considering active site water molecules in lead identification and optimization campaigns. PMID- 26271445 TI - Increase in Mexican and Latin American scientific articles on irritable bowel syndrome. AB - BACKGROUND: There is an implied perception that little scientific information on irritable bowel syndrome (IBS) comes out of Mexico and Latin America in the international medical literature, but the number and tendencies of articles from the region on IBS are not known. AIMS: To determine the number and type of Mexican and Latin American articles on IBS published between 1990-2015. METHODS: A systematic search of Medline was carried out employing the terms " Irritable Bowel Syndrome " or its abbreviation (IBS). Mexico and every other Latin American country were added to specify the search. The articles were selected if they were published in Mexico and/or the rest of Latin America, if they were international papers on IBS in the region, or if they were written by Mexican and/or Latin American authors. In addition, the articles were classified into the following categories: Reviews/Editorials/Letters to the Editor (REV/ED), Epidemiology/Quality of Life/Psychosocial Factors (EPI/QOL), Diagnostic (DX), Treatment (TX), and Translational/Pathophysiologic (TRANS) studies. RESULTS: A total of 66 articles from Mexico and 47 from Latin America were identified, but only 87.7 and 48.9%, respectively, fit the selection criteria. Category distribution was: EPI/QOL: 36.2%, REV/ED: 27.5%, TRANS: 18.8, TX: 10%, and DX: 7.5% and was similar between Mexico and Latin America (p=0.33). The year 2005 saw an increase in the number of articles in Mexico, with a peak in 2010. The figures for Latin American articles remained stable over the years, with a peak in 2012. CONCLUSIONS: A noticeable increase has been observed over the last decade in the research conducted on IBS in Mexico and Latin America. Even though the EPI/QOL studies predominate, the sophistication of research is reflected in the TRANS studies that are in third place of frequency. The information referred to herein demonstrates maturity in the field, making it possible to carry out consensuses based on local data. PMID- 26271446 TI - Relationship between hospital volume and major cardiac complications of rotational atherectomy: A nationwide retrospective cohort study in Japan. AB - BACKGROUND: Previous studies on life-threatening complications of rotational atherectomy (RA) were based on small sample sizes from a limited number of cardiovascular centers. No study has examined the relationship between hospital volume of RA and complications. METHODS: Using the Diagnosis Procedure Combination database in Japan, we identified inpatients aged >=20 years who underwent RA. Hospital volume was defined as the annual number of patients undergoing RA at each hospital and eligible patients were categorized into hospital-volume tertile (low-, medium-, and high-volume) groups. The composite outcome consisted of cardiac complications requiring urgent procedures (covered stent implantation, coronary artery bypass grafting, or pericardiocentesis) or death on the day of RA. We examined the association between hospital-volume categories and the composite outcome by using a multivariable logistic regression model fitted with a generalized estimating equation. RESULTS: A total of 9970 patients (median age, 73 years; male, 69.8%) underwent RA in 309 hospitals. The 309 hospitals were categorized into 215 low-volume (<=15/year), 67 medium-volume (16-30/year), and 27 high-volume hospitals (>=31/year). Overall, the composite outcome occurred in 62 (0.62%) patients (36 covered stent implantation, 11 coronary artery bypass grafting, 9 pericardiocentesis, and 14 death). Patients in the high-volume group had a significantly lower rate of the composite outcome (0.29%) than those in the low-volume (0.72%, p=0.010) or medium-volume group (0.89%, p=0.001). With reference to the low-volume group, risk-adjusted odds ratios (95% confidence intervals) of the medium-volume and high-volume groups for the composite outcome were 1.10 (0.64-1.89) and 0.42 (0.20-0.88), respectively. CONCLUSIONS: This study showed that higher hospital volume was significantly associated with lower complication rates of RA. Our results also suggested that the major complication rates were low even in low-volume hospitals. PMID- 26271447 TI - Donor age is a predictor of early low output after heart transplantation. AB - BACKGROUND: Using hearts from marginal donors could be related to increased risk of primary graft dysfunction and poor long-term survival. However, factors associated with delayed myocardial recovery after heart transplantation (HTx) remain unknown. We sought to clarify risk factors that predict early low output after HTx, and investigated whether early low output affects mid-term graft dysfunction. METHODS: We retrospectively analyzed patients who had undergone HTx at The University of Tokyo Hospital. We defined early low output patients as those whose cardiac index (CI) was <2.2 L/min/m(2) despite the use of intravenous inotrope at 1 week after HTx. RESULTS: We included 45 consecutive HTx recipients, and classified 11 patients into early low output group, and the others into early preserved output group. We performed univariable logistic analysis and found that donor age was the only significant factor that predicted early low output (odds ratio 1.107, 95% confidence interval 1.034-1.210, p=0.002). CI of early low output patients gradually increased and it caught up with that of early preserved output patients at 2 weeks after HTx (2.4+/-0.6 L/min/m(2) in early low output group vs 2.5+/-0.5 L/min/m(2) in early preserved output group, p=0.684). Plasma B type natriuretic peptide concentration of early low output patients was higher (1118.5+/-1250.2 pg/ml vs 526.4+/-399.5 pg/ml; p=0.033) at 1 week, 703.6+/-518.4 pg/ml vs 464.6+/-509.0 pg/ml (p=0.033) at 2 weeks, and 387.7+/-231.9 pg/ml vs 249.4+/-209.5 pg/ml (p=0.010) at 4 weeks after HTx, and it came down to that of early preserved output patients at 12 weeks after HTx. CONCLUSIONS: Donor age was a predictor of early low output after HTx. We should be careful after HTx from old donors. However, hemodynamic parameters of early low output patients gradually caught up with those of early preserved output patients. PMID- 26271448 TI - Is insulin truly harmful in diabetic patients undergoing percutaneous coronary intervention? PMID- 26271449 TI - Remote ischemic preconditioning in aortic valve surgery: Results of a randomized controlled study. AB - BACKGROUND: Although remote ischemic preconditioning (RIPC) has emerged as an attractive strategy to reduce cardiac injury in patients undergoing diverse cardiac surgical procedures, it is unclear whether RIPC has protective effects in patients undergoing aortic valve replacement surgery without coronary artery bypass grafting (CABG). METHODS: Hence, 100 adult patients undergoing elective aortic valve replacement for aortic valve stenosis, without combined surgery with CABG, were prospectively randomly assigned in a 1:1 ratio to either the RIPC group or the control group. The RIPC group underwent three cycles of 5-min inflation to 200mmHg and 5-min deflation of an automated upper-arm cuff inflator after induction of anesthesia. The control group had a deflated cuff placed on upper arm for 30min. The primary endpoint was 72-h area under curve (AUC) for troponin I (cTnI). Secondary endpoints were 72-h AUC for creatine kinase-MB isoenzyme (CK-MB) release, incidence of acute kidney injury, extubation time, length of stay in intensive care unit, and simplified acute physiology score (SAPS II). RESULTS: There were no significant differences in cTnI AUC [195+/-190 arbitrary units (a.u.) in RIPC group vs. 169+/-117 a.u. in the control group; p=0.41] and CK-MB AUC between groups. None of the other secondary endpoints differed between groups. Acute kidney injury occurred in 12 patients (24.5%) in the control group and in 13 (26.0%) in the RIPC group (p=0.86). CONCLUSIONS: RIPC did not exhibit significant cardiac or kidney protective effects in patients undergoing aortic valve replacement surgery without CABG. PMID- 26271450 TI - Identification of a novel splice variant of neuronal nitric oxide synthase, nNOSbeta, in myofilament fraction of murine cardiomyocytes. AB - Splice variant forms of neuronal nitric oxide synthase (nNOS or NOS1), nNOSalpha and nNOSMU, are well established to be functionally expressed in discrete compartments in cardiomyocytes (e.g. sarcoplasmic reticulum, SR, caveolae in plasma membrane or mitochondria). So far, whether nNOS is expressed in myofilament fraction of cardiomyocytes and the splice variant form of nNOS are unknown. Immunoblotting results using two nNOS specific antibodies (BD Transduction Laboratories aa 1095-1289 and Santa Cruz Biotechnology aa 2-300) clearly demonstrated that nNOS was abundantly expressed in myofilament-enriched fraction of cardiomyocytes. Whilst the molecular weight of nNOS in membrane/cytosol fractions was ~165 kDa, nNOS in myofilament was below 140 kDa, suggesting that the predominant splice variant of nNOS in myofilament is nNOSbeta. RT-PCR results confirmed the expressions of both nNOSalpha and nNOSbeta mRNAs in rat cardiomyocytes. Similarly, immunoprecipitation experiments using myofilament lysates of cardiomyocytes identified nNOS with low molecular weight (M.W. ~140 kDa), confirming nNOSbeta. Intriguingly, all three splice variants of nNOS were undetectable in the lysates of cardiomyocytes (including myofilament fractions) from nNOS-/- mice (which lacks nNOSalpha/MU). Furthermore, nNOSbeta expression in myofilament of cardiomyocytes was not different in hypertensive rats compared to the level expressed in sham. iTRAQ-based quantitative proteomics analysis revealed that nNOS regulates phosphorylations of ~20 proteins in cardiac myofilaments. Collectively, we provide direct evidence that different splice variants of nNOS are expressed in myofilament and membrane/cytosol fractions of cardiomyocytes. Discrete expressions of various splice variants in different compartments of cardiomyocytes suggest diverse roles nNOS play in healthy and diseased heart. PMID- 26271451 TI - Depression and the risk of autoimmune disease: a nationally representative, prospective longitudinal study. AB - BACKGROUND: Autoimmune diseases are associated with substantial morbidity and mortality, yet the etiology remains unclear. Depression has been implicated as a risk factor for various immune-related disorders but little is known about the risk of autoimmune disease. This study examined the association between depression and the risk of autoimmune disease, and investigated the temporal and dose-response nature of these relationships. METHOD: A prospective population based study including approximately 1.1 million people was conducted using linked Danish registries. Depression and autoimmune diseases were diagnosed by physicians and documented in medical records. In total, 145 217 individuals with depression were identified between 1995 and 2012. Survival analyses were used to estimate the relative risk of autoimmune disease among those with, compared to without, depression. Analyses were adjusted for gender, age, and co-morbid mental disorders. RESULTS: Depression was associated with a significantly increased risk of autoimmune disease [incidence rate ratio (IRR) 1.25, 95% CI 1.19-1.31], compared to those without a history of depression. Results suggest a general increased risk of autoimmune diseases following the onset of depression during first year (IRR 1.29, 95% CI 1.05-1.58), which remained elevated for the ensuing 11 years and beyond (IRR 1.53, 95% CI 1.34-1.76). Findings did not support a dose response relationship. CONCLUSIONS: Depression appears to be associated with an increased risk of a range of autoimmune diseases. Depression may play a role in the etiology of certain autoimmune conditions. If replicated, findings could highlight additional clinical implications in the treatment and management of depression. Future studies are needed to investigate the possible social, genetic, and neurobiological underpinnings of these relationships. PMID- 26271452 TI - Geochemical influences and mercury methylation of a dental wastewater microbiome. AB - The microbiome of dental clinic wastewater and its impact on mercury methylation remains largely unknown. Waste generated during dental procedures enters the sewer system and contributes a significant fraction of the total mercury (tHg) and methyl mercury (MeHg) load to wastewater treatment facilities. Investigating the influence of geochemical factors and microbiome structure is a critical step linking the methylating microorganisms in dental wastewater (DWW) ecosystems. DWW samples from a dental clinic were collected over eight weeks and analyzed for geochemical parameters, tHg, MeHg and bacterio-toxic heavy metals. We employed bacterial fingerprinting and pyrosequencing for microbiome analysis. High concentrations of tHg, MeHg and heavy metals were detected in DWW. The microbiome was dominated by Proteobacteria, Actinobacteria, Bacteroidetes, Chloroflexi and many unclassified bacteria. Significant correlations were found between the bacterial community, Hg levels and geochemical factors including pH and the predicted total amount (not fraction) of neutral Hg-sulfide species. The most prevalent known methylators included Desulfobulbus propionicus, Desulfovibrio desulfuricans, Desulfovibrio magneticus and Geobacter sulfurreducens. This study is the first to investigate the impact of high loads of Hg, MeHg and other heavy metals on the dental clinic wastewater microbiome, and illuminates the role of many known and unknown sulfate-reducing bacteria in Hg methylation. PMID- 26271453 TI - Boundaries for martensitic transition of (7)Li under pressure. AB - Physical properties of lithium under extreme pressures continuously reveal unexpected features. These include a sequence of structural transitions to lower symmetry phases, metal-insulator-metal transition, superconductivity with one of the highest elemental transition temperatures, and a maximum followed by a minimum in its melting line. The instability of the bcc structure of lithium is well established by the presence of a temperature-driven martensitic phase transition. The boundaries of this phase, however, have not been previously explored above 3 GPa. All higher pressure phase boundaries are either extrapolations or inferred based on indirect evidence. Here we explore the pressure dependence of the martensitic transition of lithium up to 7 GPa using a combination of neutron and X-ray scattering. We find a rather unexpected deviation from the extrapolated boundaries of the hR3 phase of lithium. Furthermore, there is evidence that, above ~3 GPa, once in fcc phase, lithium does not undergo a martensitic transition. PMID- 26271455 TI - Rapid and efficient genome-wide characterization of Xanthomonas TAL effector genes. AB - Xanthomonas TALE transcriptional activators act as virulence or avirulence factors by activating host disease susceptibility or resistance genes. Their specificity is determined by a tandem repeat domain. Some Xanthomonas pathogens contain 10-30 TALEs per strain. Although TALEs play critical roles in pathogenesis, their studies have so far been limited to a few examples, due to their highly repetitive gene structure and extreme similarity among different members, which constrict sequencing and assembling. To facilitate TALE studies, we developed an efficient and rapid pipeline for genome-wide cloning of tal genes as many as possible from a strain. Here, we report the pipeline and its use to identify all 18 tal genes from a newly isolated strain of the rice pathogen Xathomonas oryzae. Target prediction revealed a number of potential rice targets including several notable genes such as genes encoding SWEET, WRKY, Hen1, and BAK1 proteins, which provide candidates for further experimental functional analysis of the TALEs. PMID- 26271456 TI - Sub-0.5 V Highly Stable Aqueous Salt Gated Metal Oxide Electronics. AB - Recently, growing interest in implantable bionics and biochemical sensors spurred the research for developing non-conventional electronics with excellent device characteristics at low operation voltages and prolonged device stability under physiological conditions. Herein, we report high-performance aqueous electrolyte gated thin-film transistors using a sol-gel amorphous metal oxide semiconductor and aqueous electrolyte dielectrics based on small ionic salts. The proper selection of channel material (i.e., indium-gallium-zinc-oxide) and precautious passivation of non-channel areas enabled the development of simple but highly stable metal oxide transistors manifested by low operation voltages within 0.5 V, high transconductance of ~1.0 mS, large current on-off ratios over 10(7), and fast inverter responses up to several hundred hertz without device degradation even in physiologically-relevant ionic solutions. In conjunction with excellent transistor characteristics, investigation of the electrochemical nature of the metal oxide-electrolyte interface may contribute to the development of a viable bio-electronic platform directly interfacing with biological entities in vivo. PMID- 26271454 TI - ESCAP Expert Article: borderline personality disorder in adolescence: an expert research review with implications for clinical practice. AB - Borderline personality disorder (BPD) has onset in adolescence, but is typically first diagnosed in young adulthood. This paper provides a narrative review of the current evidence on diagnosis, comorbidity, phenomenology and treatment of BPD in adolescence. Instruments available for diagnosis are reviewed and their strengths and limitations discussed. Having confirmed the robustness of the diagnosis and the potential for its reliable clinical assessment, we then explore current understandings of the mechanisms of the disorder and focus on neurobiological underpinnings and research on psychological mechanisms. Findings are accumulating to suggest that adolescent BPD has an underpinning biology that is similar in some ways to adult BPD but differs in some critical features. Evidence for interventions focuses on psychological therapies. Several encouraging research studies suggest that early effective treatment is possible. Treatment development has just begun, and while adolescent-specific interventions are still in the process of evolution, most existing therapies represent adaptations of adult models to this developmental phase. There is also a significant opportunity for prevention, albeit there are few data to date to support such initiatives. This review emphasizes that there can be no justification for failing to make an early diagnosis of this enduring and pervasive problem. PMID- 26271457 TI - The pleiotropic effects of metformin: time for prospective studies. AB - The global prevalence of diabetes has risen to epidemic proportions and the trend is predicted to continue. The consequent burden of cardiovascular morbidity and mortality is a major public health concern and new treatments are required to mitigate the deleterious effects of cardiovascular disease in diabetic patients. Ischaemia-reperfusion injury is well known to exacerbate the harmful effects of acute myocardial infarction and subsequent therapeutic reperfusion, and several mechanical and pharmacological approaches to mitigating this injury have been investigated. Metformin, which is cheap, relatively safe and widely used in type 2 diabetes, is one such pharmacotherapy with considerable pre-clinical evidence for cardioprotective utility beyond its glucose-lowering effect. However, despite convincing basic evidence its translation to clinical application has largely been limited to studies of cardiovascular risk. There are several barriers to prospective randomized assessment in the context of acute myocardial infarction, not least the accessibility and already widespread use of metformin among patients with type 2 diabetes at high risk of cardiovascular events. In the place of class 1 evidence, well-designed prospective cohort studies of the potential pleiotropic utility of metformin in cardiovascular disease, and particularly its benefit in ischaemia-reperfusion injury, are needed. Given the availability of metformin worldwide, this is particularly true in low- and middle-income countries where the optimal therapy for acute myocardial infarction, primary percutaneous coronary intervention, may not be available, and instead patients are managed with thrombolysis. As this is less effective, metformin as an adjunct to thrombolysis (or PPCI) could represent an effective, cheap means of cardioprotection with global relevance. PMID- 26271458 TI - Revealing the trehalose mediated inhibition of protein aggregation through lysozyme-silver nanoparticle interaction. AB - We propose a facile and robust carbohydrate-mediated method for the prevention of nanoparticle induced denaturation and aggregation of proteins. Using label-free plasmon-enhanced Raman spectroscopy measurements, the mechanistic principles of trehalose stabilization in a model protein-nanoparticle system are elucidated for the first time, facilitating its further application in diagnostic and therapeutic nanoplex development. PMID- 26271459 TI - A Guide for a Cardiovascular Genomics Biorepository: the CATHGEN Experience. AB - The CATHeterization GENetics (CATHGEN) biorepository was assembled in four phases. First, project start-up began in 2000. Second, between 2001 and 2010, we collected clinical data and biological samples from 9334 individuals undergoing cardiac catheterization. Samples were matched at the individual level to clinical data collected at the time of catheterization and stored in the Duke Databank for Cardiovascular Diseases (DDCD). Clinical data included the following: subject demographics (birth date, race, gender, etc.); cardiometabolic history including symptoms; coronary anatomy and cardiac function at catheterization; and fasting chemistry data. Third, as part of the DDCD regular follow-up protocol, yearly evaluations included interim information: vital status (verified via National Death Index search and supplemented by Social Security Death Index search), myocardial infarction (MI), stroke, rehospitalization, coronary revascularization procedures, medication use, and lifestyle habits including smoking. Fourth, samples were used to generate molecular data. CATHGEN offers the opportunity to discover biomarkers and explore mechanisms of cardiovascular disease. PMID- 26271460 TI - Adiposity and psychosocial outcomes at ages 30 and 35. AB - PURPOSE: To examine associations between adiposity and adult psychosocial outcomes (depressive symptoms, life satisfaction, self-esteem, household income, personal income, savings/investments) in a New Zealand birth cohort, by gender. Adiposity was assessed using Body Mass Index scores classified on a 3-point scale of BMI: <25.0, overweight (25.0-29.9) or obese (>=30). METHODS: Data were gathered via face-to-face and telephone interviews for the Christchurch Health and Development Study (CHDS), comprising a birth cohort of 1265 children born in Christchurch, New Zealand, in 1977. BMI and psychosocial outcome information was collected in 2007 (30 years; n = 977) and in 2012 (35 years; n = 923). RESULTS: Population-averaged regression modeling showed evidence of statistically significant (p < 0.05) associations between increasing adiposity and adverse psychosocial outcomes for females, but not for males. After adjustment for child and family background covariates the strength of the associations for females was reduced; with four associations (depressive symptoms, life satisfaction, equivalized household income and savings/investments) remaining statistically significant (p < 0.05). In contrast, for males there was a significant (p = 0.008) positive association between adiposity and higher personal net weekly income after covariate adjustment. CONCLUSIONS: The findings suggest evidence of gender differences in the associations between adiposity and psychosocial outcomes. For females, there were small but pervasive tendencies for increasing adiposity to be related to more adverse mental health, psychological well-being and economic outcomes; whereas for males adiposity was either unrelated to these outcomes, or in the case of personal income, associated with greater economic advantage. The implications of these findings are discussed. PMID- 26271462 TI - The in vitro and in vivo effects of the low molecular weight fucoidan on the bone osteogenic differentiation properties. AB - Osteoporosis has been reported as a hidden death factor in aged people. So far, prevention and treatment therapies for osteoporosis only slow down the progress but do not treat the disease. Fucoidan has been recognized its roles in anti tumor, anti-inflammatory, anti-coagulant and antiviral activities. To date, low molecular weight (LMW) fucoidan role in bone loss disease has been not determined yet. Therefore, this study aims to figure out potential effects of LMW fucoidan in osteoporosis in vitro and in vivo. LMW fucoidan was extracted from fresh Sargassum hemiphyllum showing a significant increase in 7F2 cell viability to 150.33 +/- 6.50 % relative to normal fucoidan (130.12 +/- 5.74 %). The expression of level BMP-2, ALP, osteocalcin significantly increased with 2.28 +/- 0.06, 2.18 +/- 0.12 and 2.06 +/- 0.07 fold, respectively. The RT-PCR assay showed that LMW fucoidan increased mRNA expression of BMP-2, ALP, osteocalcin, COL I, BSP and osteonectin. Furthermore, the bone density and bone ash weight were considerably boosted by the oral administration of 280 mg/kg LMW fucoidan and 100 mg/kg calcium carbonate in C57BL/6J female aged mice. The present finding indicated that LMW fucoidan triggered osteogenic differentiation in vitro, and had an anabolic effect on bone mineralization in vivo. Dietary intake of LMW fucoidan from S. hemiphyllum suggested playing a role in the enhancement of bone loss with increasing age. PMID- 26271463 TI - Non-steroidal anti-inflammatory drugs and risk of cerebrovascular events in patients with osteoarthritis: a nested case-control study. AB - Recent studies show that the risk of cardiovascular adverse events for certain traditional non-steroidal anti-inflammatory drugs (NSAIDs) is similar to that of rofecoxib. While these results are focused on ischemic cardiomyopathy, there is little evidence concerning the risk of ischemic stroke/transient ischemic attack and hemorrhagic stroke. Additionally, there is no information on nimesulide and ketoprofen, the most frequently prescribed NSAIDs in Italy, along with diclofenac. This study aims to determine whether the use of NSAIDs is associated with an increased risk of cerebrovascular events in Italy. We performed a case control analysis nested in a cohort of patients with osteoarthritis between 2002 and 2011 who were newly treated with NSAIDs. The patients were followed until December 31, 2012. Conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI) of cerebrovascular events (index date) associated with current (until 30 days before the index date), recent (31-365 days) and past (>365 days) use of NSAIDs. Within a cohort of 29,722 patients, 1566 cases (1546 matched with controls) were identified (incidence rate = 11.0/1000 person-years). The overall rate of cerebrovascular event was not elevated with current NSAIDs overall when compared with past use. Among individual NSAIDs, diclofenac and ketoprofen were the molecules significantly associated with an increased rate of cerebrovascular events (OR = 1.53; 95% CI 1.04-2.24; OR = 1.62; 95% CI 1.02-2.58, respectively). The most frequent event was hemorrhagic stroke following the use of ketoprofen (OR = 2.09; 95% CI 1.05-4.15). Diclofenac and ketoprofen seemed to increase the risk of cerebrovascular events. These findings might influence the choice of NSAIDs according to patient characteristics. PMID- 26271464 TI - Interferon gamma-inducible protein 16 in primary Sjogren's syndrome: a novel player in disease pathogenesis? AB - INTRODUCTION: There is evidence that interferon is involved in the pathogenesis of primary Sjogren's syndrome (pSS). The interferon-inducible IFI16 protein, normally expressed in cell nuclei, may be overexpressed, mislocalized in the cytoplasm and secreted in the extracellular milieu in several autoimmune disorders. This leads to tolerance breaking to this self-protein with consequent development of anti-IFI16 antibodies. The aim of this study was to identify the pathogenic and clinical significance of IFI16 and anti-IFI16 in pSS. METHODS: IFI16 and anti-IFI16 were assessed in the serum of 67 pSS patients and over 100 healthy donors by enzyme-linked immunosorbent assay. IFI16 was also evaluated by immunohistochemistry in minor salivary glands of 15 pSS patients and 10 subjects with sicca symptoms but without any clinical, serological or histological features of pSS. RESULTS: pSS patients display higher serum levels of both IFI16 and anti-IFI16 compared to healthy donors. IFI16 concentration was directly correlated with disease duration and focus score and inversely correlated with age at diagnosis. Moreover, IFI16 positivity was associated with concurrent positivity for rheumatoid factor. Interestingly, the direct correlation between IFI16 positivity and focus score was independent of disease duration and age at diagnosis. pSS minor salivary glands display marked expression and cytoplasmic mislocalization of IFI16 by acinar and ductal epithelial cells as well as infiltrating lymphocytes and peri/intralesional endothelium compared to minor salivary glands with normal architecture or nonspecific chronic sialadenitis. Within the mononuclear cell infiltrate, IFI16 expression appears to parallel the distribution of T lymphocytes. CONCLUSION: Our data suggest that the IFI16 protein may be involved in the pathogenesis of glandular inflammation occurring in pSS. PMID- 26271465 TI - Visible-Light-Driven Photoisomerization and Increased Rotation Speed of a Molecular Motor Acting as a Ligand in a Ruthenium(II) Complex. AB - Toward the development of visible-light-driven molecular rotary motors, an overcrowded alkene-based ligand and the corresponding ruthenium(II) complex is presented. In our design, a 4,5-diazafluorenyl coordination motif is directly integrated into the motor function. The photochemical and thermal isomerization behavior has been studied by UV/Vis and NMR spectroscopy. Upon coordination to a Ru(II) bipyridine complex, the photoisomerization process can be driven by visible (lambdamax = 450 nm) instead of UV light and furthermore, a large increase of the speed of rotation is noted. DFT calculations point to a contraction of the diazafluorenyl lower half upon metal-coordination resulting in reduced steric hindrance in the "fjord region" of the molecule. Consequently, it is shown that metal-ligand interactions can play an important role in the adjustment of both photophysical and thermodynamic properties of molecular motors. PMID- 26271461 TI - Binocular pattern deprivation interferes with the expression of proteins involved in primary visual cortex maturation in the cat. AB - BACKGROUND: Binocular pattern deprivation from eye opening (early BD) delays the maturation of the primary visual cortex. This delay is more pronounced for the peripheral than the central visual field representation within area 17, particularly between the age of 2 and 4 months [Laskowska-Macios, Cereb Cortex, 2014]. RESULTS: In this study, we probed for related dynamic changes in the cortical proteome. We introduced age, cortical region and BD as principal variables in a 2-D DIGE screen of area 17. In this way we explored the potential of BD-related protein expression changes between central and peripheral area 17 of 2- and 4-month-old BD (2BD, 4BD) kittens as a valid parameter towards the identification of brain maturation-related molecular processes. Consistent with the maturation delay, distinct developmental protein expression changes observed for normal kittens were postponed by BD, especially in the peripheral region. These BD-induced proteomic changes suggest a negative regulation of neurite outgrowth, synaptic transmission and clathrin-mediated endocytosis, thereby implicating these processes in normal experience-induced visual cortex maturation. Verification of the expression of proteins from each of the biological processes via Western analysis disclosed that some of the transient proteomic changes correlate to the distinct behavioral outcome in adult life, depending on timing and duration of the BD period [Neuroscience 2013;255:99-109]. CONCLUSIONS: Taken together, the plasticity potential to recover from BD, in relation to ensuing restoration of normal visual input, appears to rely on specific protein expression changes and cellular processes induced by the loss of pattern vision in early life. PMID- 26271466 TI - Thymic emigration patterns in patients with type 2 diabetes treated with metformin. AB - Recent data suggest that thymic output, which provides the naive T cells necessary for the normal functioning of T-cell-dependent immunosurveillance cellular immunity including anti-cancer protection, can be disturbed in the course of type 2 diabetes. Metformin, an anti-diabetic drug commonly confirmed as an agent with many potential anti-cancer activities, might be helpful in this immune correction. The profile of thymic output was evaluated in the current study on the basis of the signal-joint T-cell receptor excision circle (sjTREC) concentration in peripheral blood polymorphonuclear cells and thymic emigrant content in peripheral blood evaluated from CD127 and/or CD132 antigen expression. It was revealed that recent thymic emigrants and more differentiated CD127(+) CD132(+) cell populations were decreased among naive T cells and CD8(+) T cells, whereas RTE count was increased in CD4(+) T cells, and the CD127(+) CD132(+) cell population was less numerous than in non-diabetic participants. Terminally differentiated thymic emigrants, i.e. CD127(-) CD132(+) cells, were increased in naive T cells and in CD8(+) T cells. Metformin affects mainly the early phases of thymic export, increasing CD127(+) CD132(-) and CD127(+) CD132(+) cell populations in naive T cells and the CD127(+) CD132(-) population in CD4(+) T lymphocytes. It could be concluded that type 2 diabetes deteriorates thymic immunostasis. The decreased thymic output could be compensated by metformin, especially with regard to CD4(+) naive T cells. It is the first time that therapy with metformin has been documented by us as particularly useful in the control and normalization of thymus function, regarding correction of early populations of thymic emigrants. PMID- 26271467 TI - The role of cytoplasmic p57 in invasion of hepatocellular carcinoma. AB - BACKGROUND: Our previous research suggested that p57 downregulation could accelerate the growth and invasion of hepatocellular carcinoma in vitro and in vivo. AIM: To evaluate the role of cytoplasmic p57 and its regulatory mechanism during hepatocellular carcinoma invasion. METHODS: We examined the subcellular localization of p57 by immunohistochemistry in 45 pairs of cancerous tissues and adjacent non-cancerous tissues. Moreover, we generated stable p57 knockdown hepatoma cell lines to investigate the mechanism of cytoplasmic p57-mediated regulation of invasion by immunoprecipitation, confocal immunofluorescence microscopy and western blot of nuclear and cytoplasmic extracts. RESULTS: Our results showed that cytoplasmic expression of p57 was reduced in specimens from patients with capsular invasion and metastasis (P < 0.05). Moreover, the level of p-cofilin was decreased in the group lacking cytoplasmic p57 expression (P < 0.05). Co-expression of p57 and p-cofilin was reduced in specimens from patients with tumors at later stages (III + IV), tumors showing capsular invasion and metastatic tumors. We further observed that p57 downregulation decreased the assembly of p57 and LIM domain kinase 1 and its kinase activity, subsequently reducing the level of p-cofilin in the cytoplasm. CONCLUSIONS: Cytoplasmic p57 might be a key regulator in hepatocellular carcinoma invasion via the LIM domain kinase 1/p-cofilin pathway. PMID- 26271468 TI - Self-perceived stress is associated with adiposity and atherosclerosis. The GEA Study. AB - BACKGROUND: A growing body of evidence suggests that psychological stress is an independent cardiovascular risk factor. Obesity prevalence shows accelerating trends worldwide, and is known to be associated with a range of comorbidities and survival. The aim of this study was to assess the relationship between self perceived psychological stress with parameters of adiposity, metabolic syndrome, and subclinical atherosclerosis in Mexican participants. METHODS: Metabolic Syndrome was defined using the Adult Treatment Panel III criteria, obesity was defined as BMI >30, subclinical atherosclerosis disease was determined by computed tomography, and carotid intima media thickness was determined by ultrasonography. Self-perceived psychological stress was assessed using a single item questionnaire. RESULTS: A total of 1243 control subjects were included in the sample, mean age 54.2 +/- 9 years old; the prevalence of chronic self perceived psychological stress (>5 years) was 10.13 %, female gender (62.7 %), obesity prevalence (48.4 %), and self-reporting sedentary lifestyle (56.3 %). The chronic stressed cohort presented higher subcutaneous abdominal fat content (285 vs 319 cm(2)), and carotid intima media thickness (0.63 vs 0.66 mm; p < 0.01 for both). However, after adjustment for lifestyle/social covariates (Model 1) and biological mediators (Model 2), chronic self-perceived stress was independently associated with obesity in men (OR 2.85, 95 % CI 1.51 - 5.40) and carotid atherosclerosis in women (OR 2.262, 95 % CI 1.47 - 4.67; p < 0.01 for both). CONCLUSION: Our study suggests that self-reported chronic stress is an independent risk factor for obesity in men. In addition, carotid atherosclerosis was also found to be an independent risk factor in women in a Mexican population sample. PMID- 26271471 TI - Congenital Pulmonary Vein Stenosis: Encouraging Mid-term Outcome. AB - Congenital pulmonary vein stenosis (PVS) is a rare entity with limited outcome literature. Multiple interventional approaches have evolved including surgical and catheterization techniques. Our objective is to report our center experience and to compare short-term and mid-term outcomes among these therapeutic modalities. Retrospective study on 23 patients (n = 23) with PVS that required intervention over the last 13 years (2000-2013). Patients were divided into three groups based on type of initial intervention. Of these, 10 (43.5%) had balloon angioplasty, 3 (13.0 %) had surgical dilation, and 10 (43.5%) had surgical marsupialization. Mortality and number of re-interventions were our primary outcomes. Mean age at diagnosis was 10.9 +/- 18.4 months. Mean age at initial intervention was 14.5 +/- 18.0 months. Mean pre- and post-initial intervention PVS gradients were 9.2 +/- 3.4 and 3.4 +/- 2.2 mmHg, respectively. Mean survival time and re-intervention-free survival time were 4.8 +/- 4.0 and 2.8 +/- 3.4 years. No statistical significance was found between the interventions with respect to survival time (p = 0.52) and re-intervention free time (p = 0.78). High initial pre- and post-intervention gradients were significantly associated with re-intervention-free survival (p = 0.01 and p = 0.03, respectively). Patients with bilateral disease have increased mortality (p = 0.01) and decreased 5-year survival (p = 0.009) compared to patients with unilateral disease irrespective of type of intervention. No statistically significant difference in mortality or re-intervention rate was present among these different therapeutic modalities. This study has the longest follow-up so far reported in the current literature (58 months) with overall survival of 78%. PMID- 26271470 TI - National Acute Medicine Programme--improving the care of all medical patients in Ireland. AB - BACKGROUND: The National Acute Medicine Programme (NAMP) was established to address the unsatisfactory management of acutely ill medical patients in Ireland. It aimed to improve quality of care and patient safety, streamline access to healthcare, and reduce cost through efficiency gains. METHOD: A model of care was developed to describe 4 distinct clinical pathways for medical patients streamed through acute medical assessment units. A patient flow model was used to build system capacity and predict demand for each hospital. Specific practice changes necessary were identified for each pathway. A performance framework, with national benchmarks that mirrored the model of care, was also developed. The program team met regularly with hospitals and fed back performance information and, using appreciative enquiry, supported local improvement plans. RESULTS: Thirty-two out of 33 Irish hospitals that admit acute medical patients are now operating the program. Process improvement lies at the core of all the success achieved by the program. Available inpatient data were improved and harnessed to support ongoing audit and quality improvement. A reduction of 1.6 days in average length of stay nationally was achieved between 2010 and 2013. CONCLUSION: Despite a 25% increase in hospital discharges and the severe financial constraints experienced during this implementation period, the NAMP achieved significant efficiency gains through process improvements, while ensuring patient safety and likely improving the quality of care delivered to patients in Ireland. PMID- 26271469 TI - The relevance of applying exercise training principles when designing therapeutic interventions for patients with inflammatory myopathies: a systematic review. AB - Physical exercise seems to be a safe and effective intervention in patients with inflammatory myopathy (IM). However, the optimal training intervention is not clear. To achieve an optimum training effect, physical exercise training principles must be considered and to replicate research findings, FITT components (frequency, intensity, time, and type) of exercise training should be reported. This review aims to evaluate exercise interventions in studies with IM patients in relation to (1) the application of principles of exercise training, (2) the reporting of FITT components, (3) the adherence of participants to the intervention, and (4) to assess the methodological quality of the included studies. The literature was searched for exercise studies in IM patients. Data were extracted to evaluate the application of the training principles, the reporting of and the adherence to the exercise prescription. The Downs and Black checklist was used to assess methodological quality of the included studies. From the 14 included studies, four focused on resistance, two on endurance, and eight on combined training. In terms of principles of exercise training, 93 % reported specificity, 50 % progression and overload, and 79 % initial values. Reversibility and diminishing returns were never reported. Six articles reported all FITT components in the prescription of the training though no study described adherence to all of these components. Incomplete application of the exercise training principles and insufficient reporting of the exercise intervention prescribed and completed hamper the reproducibility of the intervention and the ability to determine the optimal dose of exercise. PMID- 26271472 TI - Assessments of Coronary Artery Visibility and Radiation Dose in Infants with Congenital Heart Disease on Cardiac 128-slice CT and on Cardiac 64-slice CT. AB - The aim of this study was to compare the coronary artery visibility and radiation dose in infants with CHD on cardiac 128-slice CT and on cardiac 64-slice CT. The images of 200 patients were analyzed in this study, 100 patients were selected randomly from a group of 789 infants (<1 years old) with CHD undergoing 128-slice CT prospective ECG-triggered axial scan, and 100 were selected randomly from 911 infants with CHD undergoing 64-slice CT retrospective ECG-gated spiral scan. The visibility of coronary artery segments was graded on a four-point scale. The coronary arteries were considered to be detected or visible when grade was 2 or higher. The visibility of the coronary artery segments and the radiation dose was compared between the two groups. Except for the rate of LM (96 vs. 99%), the detection rates of the total, LAD, LCX, RCA, and the proximal segment of the RCA in the 256-slice CT group were significantly higher than those in the 64-slice CT group (51.7, 53.33, 33.67, 53.33, and 99 vs. 34.8, 34.33, 18, 30.67, and 75%, respectively). The counts of visibility score (4/3/2/1) for the LM and the proximal segment of the RCA were 62/22/12/4 and 56/20/17/7, respectively, in the 128-slice CT group and 17/42/30/1 and 9/30/38/25, respectively, in the 64-slice CT group. There were significant differences, especially for score 4 and 3, between the two groups. The radiation dose in the 128-slice CT group was significantly decreased than those in the 64-slice CT group (CTDIvol 1.88 +/- 0.51 vs. 5.61 +/- 0.63 mGy; SSDE 4.48 +/- 1.15 vs. 13.97 +/- 1.52 mGy; effective radiation dose 1.36 +/- 0.44 vs. 4.06 +/- 0.7 mSv). With reduced radiation dose, the visibility of the coronary artery in infants with CHD via prospective ECG triggered mode on a 128-slice CT is superior to that of the 64-slice CT using retrospective ECG-gated spiral mode. PMID- 26271473 TI - Response to Letter by Finsterer and Zarrouk. PMID- 26271474 TI - Familial Contributions to Self-Reported Sleep and Pain in Female Twins. AB - OBJECTIVE: The relationship between sleep quality and pain has been studied in populations with chronic pain and in nonclinical populations using experimental paradigms. Little is known about the familial contributions to this relationship. This study examines self-reported sleep quality and pain in a nonclinical sample and to explore familial (i.e., shared genetic and common family environment) confounding in those relationships. DESIGN: Cross-sectional. SUBJECTS: Ninety nine community-based female twin pairs (N = 198) with a mean age of 29 years; 72% monozygotic. METHODS: The short form McGill Pain Questionnaire (McGill), a visual analog scale (VAS), a body map, and the Pittsburgh Sleep Quality Index (PSQI) measured self-reported pain and sleep quality. Mixed model regression adjusted for age was used to examine relationships between the pain indices and PSQI in overall and within-pair models. RESULTS: Higher PSQI total scores were significantly associated with higher scores across the McGill sensory (B = 0.37, p < 0.001), affective (B = 0.16, p < 0.001), total scores (B = 0.54, p < 0.001), the VAS (B = 2.41, p < 0.001), and number of sites with any pain on the body map (B = 0.42, p = 0.001). All of these associations were diminished and rendered nonsignificant in within-pair analyses that accounted for genetic and familial factors (all p's >= 0.01; Bonferroni alpha = 0.01). CONCLUSIONS: These findings support an association between poor sleep quality and pain and suggest that this relationship may be confounded by shared genetic and environmental factors, which could elucidate biological mechanisms that underlie the development and maintenance of pain and sleep problems. PMID- 26271475 TI - Hfqs in Bacillus anthracis: Role of protein sequence variation in the structure and function of proteins in the Hfq family. AB - Hfq proteins in Gram-negative bacteria play important roles in bacterial physiology and virulence, mediated by binding of the Hfq hexamer to small RNAs and/or mRNAs to post-transcriptionally regulate gene expression. However, the physiological role of Hfqs in Gram-positive bacteria is less clear. Bacillus anthracis, the causative agent of anthrax, uniquely expresses three distinct Hfq proteins, two from the chromosome (Hfq1, Hfq2) and one from its pXO1 virulence plasmid (Hfq3). The protein sequences of Hfq1 and 3 are evolutionarily distinct from those of Hfq2 and of Hfqs found in other Bacilli. Here, the quaternary structure of each B. anthracis Hfq protein, as produced heterologously in Escherichia coli, was characterized. While Hfq2 adopts the expected hexamer structure, Hfq1 does not form similarly stable hexamers in vitro. The impact on the monomer-hexamer equilibrium of varying Hfq C-terminal tail length and other sequence differences among the Hfqs was examined, and a sequence region of the Hfq proteins that was involved in hexamer formation was identified. It was found that, in addition to the distinct higher-order structures of the Hfq homologs, they give rise to different phenotypes. Hfq1 has a disruptive effect on the function of E. coli Hfq in vivo, while Hfq3 expression at high levels is toxic to E. coli but also partially complements Hfq function in E. coli. These results set the stage for future studies of the roles of these proteins in B. anthracis physiology and for the identification of sequence determinants of phenotypic complementation. PMID- 26271477 TI - Building community resilience: business preparedness lessons in the case of Adapazari, Turkey. AB - The lack of attention paid to businesses in disaster management systems from the standpoint of state policies hampers efforts to build community resilience. This paper examines, therefore, the extent of business preparedness for disasters. Empirical research was conducted in Adapazari, Turkey, 13 years after the Izmit earthquake, which struck the northwest of the country on 17 August 1999, claiming the lives of some 17,000 people. For the study, 232 firms were selected to inquire about their preparedness before and after the event. It is hypothesised that business preparedness is influenced by the following set of variables: business size; business sector; business age; financial condition prior to the disaster; occupancy tenure; market range; education level; and previous disaster experience. In line with the findings of the research, a policy framework is constructed to rationalise the allocation of resources for building resilience at the aggregate level by facilitating business preparedness. PMID- 26271476 TI - Localization of nonpalpable pulmonary nodules using CT-guided needle puncture. AB - BACKGROUND: Surgical resection of small pulmonary nodule is challenging via thoracoscopic procedure. We describe our experience of computed tomography (CT) guided needle puncture localization of indeterminate pulmonary nodules prior to video-assisted thoracoscopic surgery (VATS). METHODS: From January 2011 to July 2014, 78 consecutive patients underwent CT-guided marking for the localization of 91 small pulmonary nodules. We retrospectively reviewed the clinical data, technical details, surgical findings and pathologic results, and complications associated with CT-guided localization. RESULTS: Seventy-eight consecutive patients (36 men and 42 women) underwent CT-guided marking localization of 91 indeterminate pulmonary nodules (62 pure ground-glass opacity nodules, 27 part solid nodules, and 2 solid nodules). The mean size of the nodules was 8.6 mm (3.0 23.0 mm). The mean pleural distance between the nodule and lung surface was 11.5 mm (3.0-31.3 mm). The mean procedure time of CT-guided localization was 15.2 min (8-42 min). All patients stood the procedures well without requiring conversion to open thoracotomy. Twenty-four patients (30.77%) developed pneumothorax after the procedures. Only one patient required retention of the puncture needle introducer for air drainage. The mean visual assessment pain score was 1.7 (0-3). Fifty-seven nodules (62.63%) were confirmed as malignances, including 45 primary lung cancer, and 34 nodules (37.37%) were confirmed as benign lesions. CONCLUSIONS: CT-guided needle puncture can be an effective and safe procedure prior to VATS, enabling accurate resection and diagnosis of small pulmonary nodules. PMID- 26271478 TI - Retinoic Acid Inhibits Adipogenesis Modulating C/EBPbeta Phosphorylation and Down Regulating Srebf1a Expression. AB - Adipogenesis comprises a complex network of signaling pathways and transcriptional cascades; the GSK3beta-C/EBPbeta-srebf1a axis is a critical signaling pathway at early stages leading to the expression of PPARgamma2, the master regulator of adipose differentiation. Previous work has demonstrated that retinoic acid inhibits adipogenesis affecting different signaling pathways. Here, we evaluated the anti-adipogenic effect of retinoic acid on the adipogenic transcriptional cascade, and the expression of adipogenic genes cebpb, srebf1a, srebf1c, pparg2, and cebpa. Our results demonstrate that retinoic acid blocks adipose differentiation during commitment, returning cells to an apparent non committed state, since they have to be newly induced to adipose conversion after the retinoid is removed from the culture medium. Retinoic acid down regulates the expression of the adipogenic genes, srebf1a, srebf1c, pparg2, and cebpa; however, it did not down regulate the expression of cebpb, but it inhibited C/EBPbeta phosphorylation at Thr188, a critical step for the progression of the adipogenic program. We also found that RA inhibition of adipogenesis did not increase the expression of dlk1, the gene encoding for Pref1, a well-known anti-adipogenic factor. PMID- 26271479 TI - A rechargeable aluminum-ion battery utilizing a copper hexacyanoferrate cathode in an organic electrolyte. AB - Reversible aluminum intercalation/deintercalation from an organic electrolyte into copper hexacyanoferrate is presented. Evidence suggest that an aluminum solute complex is the intercalating species. The system shows initial discharge capacities as high as 60 mA h g(-1) and reversible capacities between 5 and 14 mA h g(-1), with capacity typically fading after 10 to 15 cycles. PMID- 26271480 TI - Not all non-natives are equally unequal: reductions in herbivore beta-diversity depend on phylogenetic similarity to native plant community. AB - Effects of host plant alpha- and beta-diversity often confound studies of herbivore beta-diversity, hindering our ability to predict the full impact of non native plants on herbivores. Here, while controlling host plant diversity, we examined variation in herbivore communities between native and non-native plants, focusing on how plant relatedness and spatial scale alter the result. We found lower absolute magnitudes of beta-diversity among tree species and among sites on non-natives in all comparisons. However, lower relative beta-diversity only occurred for immature herbivores on phylogenetically distinct non-natives vs. natives. Locally in that comparison, non-native gardens had lower host specificity; while among sites, the herbivores supported were a redundant subset of species on natives. Therefore, when phylogenetically distinct non-natives replace native plants, the community of immature herbivores is likely to be homogenised across landscapes. Differences in communities on closely related non natives were subtler, but displayed community shifts and increased generalisation on non-natives within certain feeding guilds. PMID- 26271482 TI - The 9th Asia-Pacific Conference on Vision (APCV 2013). July 5th-8th, 2013. Suzhou, China. PMID- 26271481 TI - In Vivo anti-trypanosomal activity of dichloromethane and methanol crude leaf extracts of Dovyalis abyssinica (Salicaceae) against Trypanosoma congolense. AB - BACKGROUND: African trypanosomiasis affects both humans and livestock in sub Saharan countries including Ethiopia. Due to limitations to current chemotherapy, there is an urgent need for the development of new, safe, cheap and effective drugs. In the present study, the leaf of Dovyalis abyssinica was tested for its in vivo antitrypanosomal activity against Trypanosoma congolense field isolate on mice. METHODS: The leaf of D. abyssinica was macerated using dichloromethane and methanol. The extracts at doses of 250, 200, 150 and 100 mg/kg body weight were administered intraperitonealy daily for 7 days to mice infected with T. congolense. Following administration, parasitemia, packed cell volume, rectal temperature, body weight and survival time were monitored. RESULTS: Administration of dichloromethane and methanol extracts at 250 and 200 mg/kg reduced (p<0.05) parasitemia and rectal temperature, and improved (p<0.05) PCV, mean body weight, and mean survival time compared to dimethylsulfoxide treatment. CONCLUSION: Crude dichloromethane and methanol leaf extracts of D. abyssinica displayed anti-trypanosomal activity that may serve as lead for the development of effective alternative antitrypanosomal drugs. PMID- 26271483 TI - Cytotoxicity of the CD37 antibody BI 836826 against chronic lymphocytic leukaemia cells in combination with chemotherapeutic agents or PI3K inhibitors. PMID- 26271484 TI - Prevalence and risk factors of Helicobacter pylori infection in asymptomatic Chinese children: a prospective, cross-sectional, population-based study. AB - BACKGROUND: Limited research has been published on current Helicobacter pylori infection rate in asymptomatic children in China. AIM: To assess current Helicobacter pylori infection rate, distribution characteristics and risk factors in Chinese asymptomatic children. METHODS: A prospective, cross-sectional, population-based study was performed from 2009 to 2011 in three cities of China. Helicobacter pylori infection was diagnosed by a stool antigen test. Multi-stage cluster random sampling was used to select asymptomatic children including neonates. Socioeconomic details were obtained through a standardised questionnaire. RESULTS: Among total of 3491 children (0-18 years), the global infection rate was 6.8% and there were no significant differences between genders. Age specific infection rate between regions was significantly different (P < 0.05). The infection rate significantly increased with age (P for trend <0.01). It was low during the newborn (0.6%) to preschool period and was significantly increased in high school students (13.5%) (P < 0.01). Multivariable regression indicated that hand sanitisation, individually served meals, higher education level of mother, above average living space and residence in urban areas were significantly protective against infection (OR 0.749, 0.698, 0.720, 0.838 and 0.770 respectively). Conversely, consuming meals in unsanitised conditions, sharing towels, receiving pre-chewed food from the mother, artificial feeding and family history of gastrointestinal disease were significantly associated with the risk of infection (OR 1.200, 1.965, 2.002, 1.071 and 2.093 respectively). CONCLUSIONS: Helicobacter pylori infection rate increases with age in Chinese asymptomatic children and is common after 10 years of age. The rate of infection is related to socioeconomic status. PMID- 26271485 TI - Liver transplantation from living donors with Gilbert's syndrome is a safe procedure for both donors and recipients. AB - Liver transplantation (LT) has become a favorable therapeutic option for patients with end-stage liver diseases. Gilbert's syndrome (GS) is a benign condition characterized by intermittent mild jaundice due to unconjugated hyperbilirubinemia. It is not obvious whether living-donor liver transplantation (LDLT) from a donor with GS could result in a normal outcome for both the recipient and the donor. We aimed to determine whether right lobe hepatectomy is a safe procedure for living donors with GS and LT recipients. Between September 2011 and March 2015, 305 LDLT procedures using right lobe grafts were performed at Atasehir Memorial Hospital, Istanbul, Turkey. Nineteen of 305 LT candidates who had been diagnosed with GS were included in the current study. After a 12-h overnight fast, total and indirect bilirubin levels of donors and recipients were measured. The median follow-up after transplant was 16 months (range 3-36 months). The median age of donors was 25 (range 20-55 yr). Four donors (21%) were female, and 15 donors (89%) were male. The median age of donors was 51 (range 23 68 yr). Eleven recipients (57%) were female, and 8 (43%) were male. The median preoperative total bilirubin level of donors was 1.69 mg/dL (range 1.26-2.43 mg/dL) (normal range <1.2 mg/dL). The median total bilirubin level of donors on postoperative day 7 was 1.04 mg/dL (range 0.71-3.23 mg/dL). As our study has included a large number of donors with GS, it produced reliable evidence that right lobe hepatectomy is a safe procedure for living donors with GS and LT recipients. PMID- 26271486 TI - Engraftment and bone mass are enhanced by PTHrP 1-34 in ectopically transplanted vertebrae (vossicle model) and can be non-invasively monitored with bioluminescence and fluorescence imaging. AB - Evidence exists that parathyroid hormone-related protein (PTHrP) 1-34 may be more anabolic in bone than parathyroid hormone 1-34. While optical imaging is growing in popularity, scant information exists on the relationships between traditional bone imaging and histology and bioluminescence (BLI) and fluorescence (FLI) imaging. We aimed to evaluate the effects of PTHrP 1-34 on bone mass and determine if relationships existed between radiographic and histologic findings in bone and BLI and FLI indices. Vertebrae (vossicles) from mice coexpressing luciferase and green fluorescent protein were implanted subcutaneously into allogenic nude mice. Transplant recipients were treated daily with saline or PTHrP 1-34 for 4 weeks. BLI, FLI, radiography, histology, and uCT of the vossicles were performed over time. PTHrP 1-34 increased bioluminescence the most after 2 weeks, fluorescence at all time points, and decreased the time to peak bioluminescence at 4 weeks (P <= 0.027), the latter of which suggesting enhanced engraftment. PTHrP 1-34 maximized vertebral body volume at 4 weeks (P < 0.0001). The total amount of bone observed histologically increased in both groups at 2 and 4 weeks (P <= 0.002); however, PTHrP 1-34 exceeded time-matched controls (P <= 0.044). A positive linear relationship existed between the percentage of trabecular bone and (1) total bioluminescence (r = 0.595; P = 0.019); (2) total fluorescence (r = 0.474; P = 0.074); and (3) max fluorescence (r = 0.587; P = 0.021). In conclusion, PTHrP 1-34 enhances engraftment and bone mass, which can be monitored non-invasively by BLI and FLI. PMID- 26271487 TI - Downregulation of Critical Oncogenes by the Selective SK2 Inhibitor ABC294640 Hinders Prostate Cancer Progression. AB - The bioactive sphingolipid sphingosine-1-phosphate (S1P) drives several hallmark processes of cancer, making the enzymes that synthesize S1P, that is, sphingosine kinase 1 and 2 (SK1 and SK2), important molecular targets for cancer drug development. ABC294640 is a first-in-class SK2 small-molecule inhibitor that effectively inhibits cancer cell growth in vitro and in vivo. Given that AR and Myc are two of the most widely implicated oncogenes in prostate cancer, and that sphingolipids affect signaling by both proteins, the therapeutic potential for using ABC294640 in the treatment of prostate cancer was evaluated. This study demonstrates that ABC294640 abrogates signaling pathways requisite for prostate cancer growth and proliferation. Key findings validate that ABC294640 treatment of early-stage and advanced prostate cancer models downregulate Myc and AR expression and activity. This corresponds with significant inhibition of growth, proliferation, and cell-cycle progression. Finally, oral administration of ABC294640 was found to dramatically impede xenograft tumor growth. Together, these pre-clinical findings support the hypotheses that SK2 activity is required for prostate cancer function and that ABC294640 represents a new pharmacological agent for treatment of early stage and aggressive prostate cancer. IMPLICATIONS: Sphingosine kinase inhibition disrupts multiple oncogenic signaling pathways that are deregulated in prostate cancer. PMID- 26271488 TI - AZ17: a new bispecific drug targeting IL-6 and IL-23 with potential clinical use- improves psoriasis in a human xenograft transplantation model. AB - Targeting more than one molecule in multifactorial diseases involving several disease mediators may provide improved therapeutic efficacy. Psoriasis is a multifactorial disease in which interleukin (IL)-6 and IL-23 are important disease mediators because they facilitate development of Th17 cells; widely accepted to be associated with psoriasis. To meet the need for new therapeutics, we aimed to create a clinically relevant bispecific drug, by combining the inhibitory properties of anti-IL-6 and anti-IL-23 antibodies, exhibiting high affinity, high stability and the ability to be produced in high yield. The bispecific molecule AZ17 was created by combining high affinity binding domains originating from monoclonal antibodies targeting human IL-6 and IL-23. To allow for high and efficient production, AZ17 was assembled by site-specific bioconjugation from two individual single chain fragment variables that were synthesized separately in Escherichia coli. To improve stability and extend pharmacokinetics, a flexible poly-ethylene glycol molecule was used as linker. In preclinical psoriasis models, AZ17 reduced IL-23-induced ear inflammation and improved psoriasis in a xenograft transplantation model where psoriasis skin is transplanted onto immune-deficient mice. The data presented here suggest AZ17 to be a promising drug candidate in psoriasis and other inflammatory diseases associated with Th17 cell development. PMID- 26271489 TI - Heart-Focused Anxiety in Patients With Noncardiac Chest Pain: Structure and Validity. AB - Heart-focused anxiety (HFA) is a fear of cardiac sensations driven by worries of physical health catastrophe. HFA is impairing and distressing and has been shown to disproportionately affect individuals with noncardiac chest pain (NCCP), chest pain that persists in the absence of an identifiable source. The Cardiac Anxiety Questionnaire (CAQ) is a measure designed to assess HFA. The aim of this study was to evaluate the psychometric properties and factor structure of the CAQ in a sample of 229 adults diagnosed with NCCP. Results demonstrated that the CAQ is a useful measure of HFA in patients with NCCP and that a four-factor model including fear of cardiac sensations, avoidance of activities that elicit cardiac sensations, heart-focused attention, and reassurance seeking was the best fit for the data. Additionally, associations between CAQ subscales and two measures of health-related behaviors-pain-related interference and health care utilization provided evidence of concurrent validity. Treatment implications are also discussed. PMID- 26271490 TI - Are microRNAs opening up a new world of regulation? PMID- 26271491 TI - The truths we seek and the randomised trial in orthopaedic surgery. PMID- 26271493 TI - Differences between hypothetical and experience-based value sets for EQ-5D used in Sweden: Implications for decision makers. AB - AIMS: A number of value sets are available today for converting EQ-5D questionnaire responses to quality-adjusted life year-weights used in health economic evaluations. The aim of this study is to analyse the differences between the commonly used hypothetical UK value set and the newly introduced Swedish experience-based value set and to evaluate health economic implications of such differences on policy decisions. METHODS: Differences between the two value sets were studied using two methods: a comparison of health states and improvements as well as an empirical comparison. In the comparison of health states and improvements, the valuations of all EQ-5D states and all pure improvements were compared. In the empirical study, a database of 23,925 individuals was used to identify patient groups that could be affected by the implementation of the Swedish experience-based value set. RESULTS: The comparison of health states and possible improvements showed that only three health states were assigned a lower quality-adjusted life year-weight and most improvements were given smaller absolute values if the experience-based value set was used. The empirical comparison showed that severe conditions were assigned higher values when using the experience-based value set. CONCLUSIONS: The Swedish experience-based value set seems to render a higher estimated level of health-related quality of life in virtually all health conditions compared to the hypothetical UK value set. In extension, health-related quality of life enhancing interventions are likely to be given higher priority in decision-making situations where hypothetical values are used to construct quality-adjusted life year-weights. In situations where experience-based quality-adjusted life year-weights are used, life-prolonging interventions would be prioritised. PMID- 26271492 TI - Systematic review on the prevalence, frequency and comparative value of adverse events data in social media. AB - AIM: The aim of this review was to summarize the prevalence, frequency and comparative value of information on the adverse events of healthcare interventions from user comments and videos in social media. METHODS: A systematic review of assessments of the prevalence or type of information on adverse events in social media was undertaken. Sixteen databases and two internet search engines were searched in addition to handsearching, reference checking and contacting experts. The results were sifted independently by two researchers. Data extraction and quality assessment were carried out by one researcher and checked by a second. The quality assessment tool was devised in-house and a narrative synthesis of the results followed. RESULTS: From 3064 records, 51 studies met the inclusion criteria. The studies assessed over 174 social media sites with discussion forums (71%) being the most popular. The overall prevalence of adverse events reports in social media varied from 0.2% to 8% of posts. Twenty nine studies compared the results from searching social media with using other data sources to identify adverse events. There was general agreement that a higher frequency of adverse events was found in social media and that this was particularly true for 'symptom' related and 'mild' adverse events. Those adverse events that were under-represented in social media were laboratory-based and serious adverse events. CONCLUSIONS: Reports of adverse events are identifiable within social media. However, there is considerable heterogeneity in the frequency and type of events reported, and the reliability or validity of the data has not been thoroughly evaluated. PMID- 26271494 TI - Construction grammar. AB - Construction grammar, or constructionist approaches more generally, emphasize the function of particular constructions as well as their formal properties. Constructions vary in their degree of generality, from words to idioms to more abstract patterns such as argument structure constructions, topicalization, and passive. There is also no division drawn between semantics and pragmatics, as all conventional aspects of constructions are encoded within the constructions themselves; thus constructions can include information about information structure, register, or genre. The majority of constructionist approaches are also usage based, in that they recognize that we retain a great deal of item specific information. An important desideratum of constructionist approaches is that they interface naturally with what we know about language acquisition, language change, and language typology. In order to capture generalizations within a given language, constructions are related via an inheritance hierarchy, with more abstract, productive constructions being directly related to their more idiomatic instantiations. The functions of particular constructions as well as domain general cognitive and social cognition are appealed in order to capture cross-linguistically valid typological generalizations. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271495 TI - Memory systems. AB - The idea that there are multiple memory systems can be traced to early philosophical considerations and introspection. However, the early experimental work considered memory a unitary phenomenon and focused on finding the mechanism upon which memory is based. A full reconciliation of debates about that mechanism, and a coincidental rediscovery of the idea of multiple memory systems, emerged from studies in the cognitive neuroscience of memory. This research has identified three major forms of memory that have distinct operating principles and are supported by different brain systems. These include: (1) a cortical hippocampal circuit that mediates declarative memory, our capacity to recollect facts and events; (2) procedural memory subsystems involving a cortical-striatal circuit that mediates habit formation and a brainstem-cerebellar circuit that mediates sensorimotor adaptations; and (3) a circuit involving subcortical and cortical pathways through the amygdala that mediates the attachment of affective status and emotional responses to previously neutral stimuli. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271496 TI - Sleep and cognition. AB - Sleep is a complex physiologic state, the importance of which has long been recognized. Lack of sleep is detrimental to humans and animals. Over the past decade, an important link between sleep and cognitive processing has been established. Sleep plays an important role in consolidation of different types of memory and contributes to insightful, inferential thinking. While the mechanism by which memories are processed in sleep remains unknown, several experimental models have been proposed. This article explores the link between sleep and cognition by reviewing (1) the effects of sleep deprivation on cognition, (2) the influence of sleep on consolidation of declarative and non-declarative memory, and (3) some proposed models of how sleep facilitates memory consolidation in sleep. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271498 TI - Moral psychology (ethics). AB - This article examines a selection of currently lively debates in the quickly evolving, interdisciplinary field of moral psychology. Topics discussed include the possibility of amoralism, the nature of rationality, the (ir)rationality of emotions and intuitions, the psychology of cooperation and of (rational) commitment, weakness of will, free will, and the assignment of moral responsibility. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271497 TI - Model-based approaches to neuroimaging: combining reinforcement learning theory with fMRI data. AB - The combination of functional magnetic resonance imaging (fMRI) with computational models for a given cognitive process provides a powerful framework for testing hypotheses about the neural computations underlying such processes in the brain. Here, we outline the steps involved in implementing this approach with reference to the application of reinforcement learning (RL) models that can account for human choice behavior during value-based decision making. The model generates internal variables which can be used to construct fMRI predictor variables and regressed against individual subjects' fMRI data. The resulting regression coefficients reflect the strength of the correlation with blood oxygenation level dependent (BOLD) activity and the relevant internal variables from the model. In the second part of this review, we describe human neuroimaging studies that have employed this analysis strategy to identify brain regions involved in the computations mediating reward-related decision making. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271499 TI - The acquisition of semantics. AB - This review piece looks at how children acquire various elements of linguistic meaning. It considers issues in the acquisition of word meaning, argument structure, tense and aspect, and quantification and scope. For each of these areas, it considers the problems they pose for the acquisition process in general, reviews basic findings from the field of acquisition, and identifies outstanding questions in the field. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271500 TI - Simulation theory. AB - Simulation plays a significant role in human cognition. This article reviews evidence for a simulational account of mind reading. Drawing on findings in developmental psychology and cognitive neuroscience, it shows that mind reading involves the imitation, copying, or reexperience of the mind reading target's mental processes. The article also introduces evidence for simulational accounts of episodic memory and prospection. It identifies relevant similarities between mind reading, memory, and prospection as well as independent evidence for a role for simulation in memory. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271501 TI - Epiphenomenalism. AB - Epiphenomenalists hold that mental properties are not reducible to neural properties and are not efficacious. The view and its motivations are explained for two kinds of mental properties. Objections, and replies on behalf of epiphenomenalism, are considered. While strict epiphenomenalism is a philosophical view, there are related views that have some empirical support. Examples of this work are discussed, and their relation to the strictly philosophical view is explained. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271502 TI - Language and conceptual development. AB - Linguistic and conceptual development converge crucially in the process of early word learning. Acquiring a new word requires the child to identify a conceptual unit, identify a linguistic unit, and establish a mapping between them. On the conceptual side, the child has to not only identify the relevant part of the scene being labeled, but also isolate a concept at the correct level of abstraction-the word 'dog' must be mapped to the concept dog and not to the concepts petting or collie, for example. On the linguistic side, the child must use the syntactic context in which the word appears to determine its grammatical category (e.g., noun, verb, adjective). But she also uses syntactic information, along with observation of the world and social-communicative cues, to make guesses at which concept the word picks out as well as its level of abstraction. We present evidence that young learners learn new words rapidly and extend them appropriately. However, the relative import of observational and linguistic cues varies as a function of the kind of word being acquired, with verbs requiring a richer set of conceptual and linguistic cues than nouns. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271503 TI - Bilingualism. AB - The cognitive and linguistic processes involved in the acquisition and use of two languages are systematically different from those processes engaged in monolingual language use, leading to detectable changes in language and cognitive outcomes for bilinguals. The present article describes these differences and offers speculation on possible mechanisms. Measures of linguistic proficiency and processing are often poorer in bilinguals than in monolinguals: bilingual children have a smaller vocabulary in each language than comparable monolingual children in that language and bilingual adults take longer to retrieve specific words than monolinguals. In contrast, measures of nonverbal executive control, including the ability to selectively attend to relevant information, inhibit distraction, and shift between tasks is generally better in bilinguals than in monolinguals. These two types of outcomes are illustrated and explained through behavioral and neuroimaging evidence. The implications of these effects of bilingualism on cognitive and linguistic processing are considered in terms of both their clinical and theoretical consequences. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271504 TI - Working memory. AB - The working memory system maintains the limited information that can be kept in mind at one time. These memories are distinct from the vast amount of information stored in long-term memory. Here we give a brief summary of findings over the past half-century in the areas of working memory that we see as particularly important for understanding its nature. We discuss several current controversies, including whether there are different systems or brain modules for different kinds of working memory, why we lose items from working memory, and how individuals and age groups differ. We try to describe what is and is not known. Last, a discussion of findings from neuroimaging helps to constrain working memory theory. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271505 TI - Embodiment as a unifying perspective for psychology. AB - A basic claim of the embodiment framework is that all psychological processes are influenced by body morphology, sensory systems, motor systems, and emotions. As such, the framework holds the promise of providing a unifying perspective for psychological research. This article begins with a sketch of several arguments, from evolution to philosophy, as to why the embodiment framework is a good bet. These arguments are followed by a review of approaches to embodiment, including those from cognitive linguistics, perceptual symbol theory, and action-based theories. Finally, examples are provided for how a unifying perspective might work for cognition (including language and memory), cognitive and social development, social psychology, neuroscience, clinical psychology, and psychology applied to education. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271506 TI - The development of stereotyping and exclusion. AB - This article reviews the developmental science literature on stereotyping and exclusion, with a focus on gender, race, and ethnicity. Stereotyping of others, which is defined as the attribution of traits to individuals based on group membership, is often used to justify exclusion of others in social group contexts. This review includes a focus on the links between these two constructs. Research on stereotyping and exclusion has drawn on several theoretical traditions, including social domain theory, social identity developmental theory, and subjective group dynamics theory, which are also discussed in the context of the research findings. Key findings on stereotyping include categorization and classification in relationship with decreased in-group bias, and the role of stereotypes in encoding information. Findings on exclusion include the use of available information to make judgments, preferences for in-group members who are normative and out-group members who are deviant, the increased importance, with age, of group functioning in exclusion decisions, and decreased negative evaluation of in-group members who partake in exclusionary behaviors. Though little research has explicitly studied the links between stereotyping and exclusion from groups, this review describes the current literature in both areas and suggests future directions for research. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271507 TI - Hormonal effects on the plasticity of cognitive brain functions. AB - Sex hormones have powerful neuronal actions in the brain and affect the interaction between functionally linked cortical areas within and across cerebral hemispheres, probably via their neuromodulatory properties on gamma-aminobutyric acid and glutamate receptors. Menstrual cycle-related dynamic fluctuations in functional cerebral asymmetries and interhemispheric crosstalk have been shown to be a useful experimental model to investigate the activating effects of sex hormones on cognitive brain functions, particularly those of estradiol and progesterone. Besides a better understanding of sex hormonal effects on cognitive brain functions, this research may significantly contribute to addressing the question of whether sex differences in cognitive brain functioning truly exist and where they originate from. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271508 TI - Neural basis of thinking: laboratory problems versus real-world problems. AB - Cognitive psychologists have long argued about the reality and significance of the distinction between well-structured and ill-structured problems. Laboratory problems are usually well-structured, whereas real-world problems have both well structured and ill-structured components. This article shows how the neuropsychological data reinforce this distinction and suggests how this distinction may help to explain a puzzle about discontinuous performance of some neurological patients in laboratory and real-world problem situations. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271509 TI - Direct intercellular communications dominate the interaction between adipose derived MSCs and myofibroblasts against cardiac fibrosis. AB - The onset of cardiac fibrosis post myocardial infarction greatly impairs the function of heart. Recent advances of cell transplantation showed great benefits to restore myocardial function, among which the mesenchymal stem cells (MSCs) has gained much attention. However, the underlying cellular mechanisms of MSC therapy are still not fully understood. Although paracrine effects of MSCs on residual cardiomyocytes have been discussed, the amelioration of fibrosis was rarely studied as the hostile environment cannot support the survival of most cell populations and impairs the diffusion of soluble factors. Here in order to decipher the potential mechanism of MSC therapy for cardiac fibrosis, we investigated the interplay between MSCs and cardiac myofibroblasts (mFBs) using interactive co-culture method, with comparison to paracrine approaches, namely treatment by MSC conditioned medium and gap co-culture method. Various fibrotic features of mFBs were analyzed and the most prominent anti-fibrosis effects were always obtained using direct co-culture that allowed cell-to-cell contacts. Hepatocyte growth factor (HGF), a well-known anti-fibrosis factor, was demonstrated to be a major contributor for MSCs' anti-fibrosis function. Moreover, physical contacts and tube-like structures between MSCs and mFBs were observed by live cell imaging and TEM which demonstrate the direct cellular interactions. PMID- 26271510 TI - The use of heart rate variability measures as indicators of autonomic nervous modulation must be careful in patients after orthotopic heart transplantation. AB - The precise relation between heart rate variability (HRV) and autonomic re innervation has not been established explicitly in patients after orthotopic heart transplantation (OHT), but can be inferred from the fact that the HRV is reduced immediately after OHT and may increase gradually with time. The aim of this study was to investigate the residual HRV in patients about 1-2 years after OHT, as compared with patients after coronary artery bypass graft (CABG) surgery. Thirteen patients who had received OHT and 14 patients who had received CABG surgery were recruited. HRV analysis was performed and the HRV measures in supine position were compared between these two groups of patients. We found that the mean (mRRI), standard deviation and coefficient of variation of RR intervals, total power, very low frequency power (VLFP), low frequency power, high frequency power (HFP), normalized VLFP (nVLFP) and low-/high-frequency power ratio in the OHT group were all significantly decreased, while the heart rate (HR) and normalized HFP (nHFP) were significantly increased, as compared with the CABG group. The decrease in HRV was more severe in the VLFP region. A smaller nVLFP and a greater nHFP were associated with a smaller mRRI and a larger HR in the OHT patients. The slope of the power law relation of HRV became positive in OHT patients, instead of negative in CABG patients. We conclude that patients after OHT have residual HRV which were characterized by severely depressed time and frequency domain HRV, increased HR and nHFP, decreased nVLFP, and positive slope of the power-law relation of HRV. The use of nHFP as the indicator of vagal modulation and the use of nVLFP as the indicator of renin-angiotensin modulation, thermoregulation and vagal withdrawal must be careful in the OHT patients. PMID- 26271511 TI - Evaluation of a fiber-optic technique for recording intramuscular pressure in the human leg. AB - To evaluate a forward-sensing fiber-optic pressure technique for recording of intramuscular pressure (IMP) in the human leg and investigate factors that may influence IMP measurements used in diagnosing compartment syndromes. IMP in the tibialis anterior muscle was recorded simultaneously by a fiber-optic technique and needle-injection technique in 12 legs of 7 healthy subjects. Both measurement catheters were placed in parallel with the muscle fibers to the same depth, as verified by sonography. IMP recordings were performed at rest before, during and after applying a model of abnormally elevated IMP (simulated compartment syndrome). IMP was elevated by venous obstruction induced by a thigh tourniquet of a casted leg. IMP was also measured during injections of 0.1 ml of saline into the muscle through the catheters. IMP at baseline was 5.1 (SD = 2.6) mmHg measured with the fiber-optic technique and 7.1 (SD = 2.5) mmHg with the needle injection technique (p < 0.001). It increased to 48.5 (SD = 6.9) mmHg and 47.6 (SD = 6.6) mmHg respectively, during simulated compartment syndrome. IMP increased significantly following injection of 0.1 ml of saline, measured by both techniques. It remained increased 1 min after injection. The fiber-optic technique was able to record pulse-synchronous IMP oscillations. The fiber-optic technique may be used for IMP measurements in a muscle with both normal and abnormally elevated IMP. It has good dynamic properties allowing for measurement of IMP oscillations. Saline injection used with needle-injection systems to ensure catheter patency compromises IMP readings at least one minute after injection. PMID- 26271512 TI - Computerized Dental Comparison: A Critical Review of Dental Coding and Ranking Algorithms Used in Victim Identification. AB - Comparison of antemortem and postmortem dental records is a leading method of victim identification, especially for incidents involving a large number of decedents. This process may be expedited with computer software that provides a ranked list of best possible matches. This study provides a comparison of the most commonly used conventional coding and sorting algorithms used in the United States (WinID3) with a simplified coding format that utilizes an optimized sorting algorithm. The simplified system consists of seven basic codes and utilizes an optimized algorithm based largely on the percentage of matches. To perform this research, a large reference database of approximately 50,000 antemortem and postmortem records was created. For most disaster scenarios, the proposed simplified codes, paired with the optimized algorithm, performed better than WinID3 which uses more complex codes. The detailed coding system does show better performance with extremely large numbers of records and/or significant body fragmentation. PMID- 26271513 TI - Phosphoinositide 3-Kinase-C2alpha Regulates Polycystin-2 Ciliary Entry and Protects against Kidney Cyst Formation. AB - Signaling from the primary cilium regulates kidney tubule development and cyst formation. However, the mechanism controlling targeting of ciliary components necessary for cilium morphogenesis and signaling is largely unknown. Here, we studied the function of class II phosphoinositide 3-kinase-C2alpha (PI3K-C2alpha) in renal tubule-derived inner medullary collecting duct 3 cells and show that PI3K-C2alpha resides at the recycling endosome compartment in proximity to the primary cilium base. In this subcellular location, PI3K-C2alpha controlled the activation of Rab8, a key mediator of cargo protein targeting to the primary cilium. Consistently, partial reduction of PI3K-C2alpha was sufficient to impair elongation of the cilium and the ciliary transport of polycystin-2, as well as to alter proliferation signals linked to polycystin activity. In agreement, heterozygous deletion of PI3K-C2alpha in mice induced cilium elongation defects in kidney tubules and predisposed animals to cyst development, either in genetic models of polycystin-1/2 reduction or in response to ischemia/reperfusion-induced renal damage. These results indicate that PI3K-C2alpha is required for the transport of ciliary components such as polycystin-2, and partial loss of this enzyme is sufficient to exacerbate the pathogenesis of cystic kidney disease. PMID- 26271517 TI - Sonochemical Synthesis of Hydrophilic Drug Loaded Multifunctional Bovine Serum Albumin Nanocapsules. AB - A facile sonochemical approach is designed to fabricate protein nanocapsules for hydrophilic drugs (HDs), and HD-loaded multifunctional bovine serum albumin (BSA) nanocapsules (MBNCs) have been prepared for the first time. The as-synthesized HD loaded MBNCs have a satisfying size range and an excellent magnetic responsive ability. Moreover, high-dose hydrophilic drugs could be loaded into the MBNCs. As carriers, HD-loaded MBNCs also show attractive redox-responsive controlled release ability for hydrophilic drugs and could be internalized selectively by the tumor cells through the folate-mediated endocytosis. PMID- 26271518 TI - A rehabilitation training partnership in Madagascar. AB - We describe here the development of a mid-level training programme for doctors in Madagascar to direct regional and national rehabilitation services. Eight doctors enrolled and all gained their diplomas and have gone on to form the Association of Physical and Rehabilitation Medicine of Madagascar, which is leading further training and service developments. The course was specific to Madagascar's needs, and was devised according to the vision of the senior rehabilitation specialist in the Ministry of Health in Madagascar with support from the University of Antananarivo. The syllabus was developed with a senior Rehabilitation Medicine consultant responsible for setting up a comprehensive range of services and teaching in a University teaching hospital in the UK. Major barriers to success include the economic and political situation in Madagascar, which worsened steadily over the period of the training, the lack of resources for health, rehabilitation and rehabilitation workshops, and the withdrawal of aid. The sustainability of the training and the improved services that have been initiated will be evaluated, but these will be influenced by the situation of the country. It is hoped that this description of a highly practical training using modern teaching methods will be of use in other low-resource countries. Much of the teaching input was given by clinicians from a UK teaching hospital, and this resource will continue to be needed. PMID- 26271519 TI - Chronic Eccentric Exercise and the Older Adult. AB - Eccentric exercise has gained increasing attention as a suitable and promising intervention to delay or mitigate the known physical and physiological declines associated with aging. Determining the relative efficacy of eccentric exercise when compared with the more conventionally prescribed traditional resistance exercise will support evidence-based prescribing for the aging population. Thus, original research studies incorporating chronic eccentric exercise interventions in the older adult population were included in this review. The effects of a range of eccentric exercise modalities on muscular strength, functional capacity, body composition, muscle architecture, markers of muscle damage, the immune system, cardiovascular system, endocrine system, and rating of perceived exertion were all reviewed as outcomes of particular interest in the older adult. Muscular strength was found to increase most consistently compared with results from traditional resistance exercise. Functional capacity and body composition showed significant improvements with eccentric endurance protocols, especially in older, frail or sedentary cohorts. Muscle damage was avoided with the gradual progression of novel eccentric exercise, while muscle damage from intense acute bouts was significantly attenuated with repeated sessions. Eccentric exercise causes little cardiovascular stress; thus, it may not generate the overload required to elicit cardiovascular adaptations. An anabolic state may be achievable following eccentric exercise, while improvements to insulin sensitivity have not been found. Finally, rating of perceived exertion during eccentric exercise was often significantly lower than during traditional resistance exercise. Overall, evidence supports the prescription of eccentric exercise for the majority of outcomes of interest in the diverse cohorts of the older adult population. PMID- 26271520 TI - A Review of Material Degradation Modelling for the Analysis and Design of Bioabsorbable Stents. AB - The field of percutaneous coronary intervention has witnessed many progressions over the last few decades, more recently with the advancement of fully degradable bioabsorbable stents. Bioabsorbable materials, such as metallic alloys and aliphatic polyesters, have the potential to yield stents which provide temporary support to the blood vessel and allow native healing of the tissue to occur. Many chemical and physical reactions are reported to play a part in the degradation of such bioabsorbable materials, including, but not limited to, corrosion mechanisms for metals and the hydrolysis and crystallization of the backbone chains in polymers. In the design and analysis of bioabsorbable stents it is important to consider the effect of each aspect of the degradation on the material's in vivo performance. The development of robust computational modelling techniques which fully capture the degradation behaviour of these bioabsorbable materials is a key factor in the design of bioabsorable stents. A critical review of the current computational modelling techniques used in the design and analysis of these next generation devices is presented here, with the main accomplishments and limitations of each technique highlighted. PMID- 26271515 TI - Role of the steroidogenic acute regulatory protein in health and disease. AB - Steroid hormones are an important class of regulatory molecules that are synthesized in steroidogenic cells of the adrenal, ovary, testis, placenta, brain, and skin, and influence a spectrum of developmental and physiological processes. The steroidogenic acute regulatory protein (STAR) predominantly mediates the rate-limiting step in steroid biosynthesis, i.e., the transport of the substrate of all steroid hormones, cholesterol, from the outer to the inner mitochondrial membrane. At the inner membrane, cytochrome P450 cholesterol side chain cleavage enzyme cleaves the cholesterol side chain to form the first steroid, pregnenolone, which is converted by a series of enzymes to various steroid hormones in specific tissues. Both basic and clinical evidence have demonstrated the crucial involvement of the STAR protein in the regulation of steroid biosynthesis. Multiple levels of regulation impinge on STAR action. Recent findings demonstrate that hormone-sensitive lipase, through its action on the hydrolysis of cholesteryl esters, plays an important role in regulating STAR expression and steroidogenesis which involve the liver X receptor pathway. Activation of the latter influences macrophage cholesterol efflux that is a key process in the prevention of atherosclerotic cardiovascular disease. Appropriate regulation of steroid hormones is vital for proper functioning of many important biological activities, which are also paramount for geriatric populations to live longer and healthier. This review summarizes the current level of understanding on tissue-specific and hormone-induced regulation of STAR expression and steroidogenesis, and provides insights into a number of cholesterol and/or steroid coupled physiological and pathophysiological consequences. PMID- 26271521 TI - A Comparative Study of Collagen Matrix Density Effect on Endothelial Sprout Formation Using Experimental and Computational Approaches. AB - A thorough understanding of determining factors in angiogenesis is a necessary step to control the development of new blood vessels. Extracellular matrix density is known to have a significant influence on cellular behaviors and consequently can regulate vessel formation. The utilization of experimental platforms in combination with numerical models can be a powerful method to explore the mechanisms of new capillary sprout formation. In this study, using an integrative method, the interplay between the matrix density and angiogenesis was investigated. Owing the fact that the extracellular matrix density is a global parameter that can affect other parameters such as pore size, stiffness, cell matrix adhesion and cross-linking, deeper understanding of the most important biomechanical or biochemical properties of the ECM causing changes in sprout morphogenesis is crucial. Here, we implemented both computational and experimental methods to analyze the mechanisms responsible for the influence of ECM density on the sprout formation that is difficult to be investigated comprehensively using each of these single methods. For this purpose, we first utilized an innovative approach to quantify the correspondence of the simulated collagen fibril density to the collagen density in the experimental part. Comparing the results of the experimental study and computational model led to some considerable achievements. First, we verified the results of the computational model using the experimental results. Then, we reported parameters such as the ratio of proliferating cells to migrating cells that was difficult to obtain from experimental study. Finally, this integrative system led to gain an understanding of the possible mechanisms responsible for the effect of ECM density on angiogenesis. The results showed that stable and long sprouts were observed at an intermediate collagen matrix density of 1.2 and 1.9 mg/ml due to a balance between the number of migrating and proliferating cells. As a result of weaker connections between the cells and matrix, a lower collagen matrix density (0.7 mg/ml) led to unstable and broken sprouts. However, higher matrix density (2.7 mg/ml) suppressed sprout formation due to the high level of matrix entanglement, which inhibited cell migration. This study also showed that extracellular matrix density can influence sprout branching. Our experimental results support this finding. PMID- 26271522 TI - Cervical Spine Disc Deformation During In Vivo Three-Dimensional Head Movements. AB - Although substantial research demonstrates that intervertebral disc cells respond to mechanical signals, little research has been done to characterize the in vivo mechanical environment in the disc tissue. The objective of this study was to estimate cervical disc strain during three-dimensional head movements. Twenty nine young healthy adults performed full range of motion flexion/extension, lateral bending, and axial rotation of the head within a biplane radiography system. Three-dimensional vertebral kinematics were determined using a validated model-based tracking technique. A computational model used these kinematics to estimate subject-specific intervertebral disc deformation (C3-4 to C6-7). Peak compression, distraction and shear strains were calculated for each movement, disc level, and disc region. Peak compression strain and peak shear strain were highest during flexion/extension (mean +/- 95% confidence interval) (32 +/- 3 and 86 +/- 8%, respectively), while peak distraction strain was highest during lateral bending (57 +/- 5%). Peak compression strain occurred at C4-5 (33 +/- 4%), while peak distraction and shear strain occurred at C3-4 (54 +/- 8 and 83 +/ 11%, respectively). Peak compression, distraction, and shear strains all occurred in the posterior-lateral annulus (48 +/- 4, 80 +/- 8, and 109 +/- 12%, respectively). These peak strain values may serve as boundary conditions for in vitro loading paradigms that aim to assess the biologic response to physiologic disc deformations. PMID- 26271523 TI - The self-harm inventory: A meta-analysis of its relationship to the personality diagnostic questionnaire-4 as a measure of borderline personality disorder. AB - OBJECTIVE: The purpose of the present study was to further examine the efficacy of the Self-Harm Inventory (SHI) as a proxy measure in diagnosing borderline personality disorder, with the comparison measure being the Personality Diagnostic Questionnaire-4 (PDQ-4). METHODS: We undertook a meta-analysis of data from our previous studies of psychiatric inpatients (N = 270) and internal medicine outpatients (N = 2587), all of whom completed both the SHI and the PDQ 4. RESULTS: Scores on the SHI and PDQ-4 were strongly correlated, especially after correcting for attenuation due to measurement unreliability (0.78 in the compiled inpatient psychiatry sample and 0.83 in the compiled internal medicine sample). Moreover, the SHI demonstrated statistically significantly greater reliability coefficients relative to the PDQ-4. CONCLUSIONS: Based upon comparison with the PDQ-4, the SHI appears to be an efficacious proxy measure of borderline personality symptomatology in both psychiatric inpatient samples and primary care outpatient samples. PMID- 26271514 TI - Insights into the molecular mechanisms of diabetes-induced endothelial dysfunction: focus on oxidative stress and endothelial progenitor cells. AB - Diabetes mellitus is a heterogeneous, multifactorial, chronic disease characterized by hyperglycemia owing to insulin insufficiency and insulin resistance (IR). Recent epidemiological studies showed that the diabetes epidemic affects 382 million people worldwide in 2013, and this figure is expected to be 600 million people by 2035. Diabetes is associated with microvascular and macrovascular complications resulting in accelerated endothelial dysfunction (ED), atherosclerosis, and cardiovascular disease (CVD). Unfortunately, the complex pathophysiology of diabetic cardiovascular damage is not fully understood. Therefore, there is a clear need to better understand the molecular pathophysiology of ED in diabetes, and consequently, better treatment options and novel efficacious therapies could be identified. In the light of recent extensive research, we re-investigate the association between diabetes-associated metabolic disturbances (IR, subclinical inflammation, dyslipidemia, hyperglycemia, dysregulated production of adipokines, defective incretin and gut hormones production/action, and oxidative stress) and ED, focusing on oxidative stress and endothelial progenitor cells (EPCs). In addition, we re-emphasize that oxidative stress is the final common pathway that transduces signals from other conditions either directly or indirectly-leading to ED and CVD. PMID- 26271525 TI - Routine use of U-tube drainage for necrotizing pancreatitis: a step toward less morbidity and resource utilization. AB - BACKGROUND: A U-tube drainage catheter (UTDC) is a novel intervention for necrotizing pancreatitis, with multiple benefits: bidirectional flushing, greater interface with large fluid collections, less risk of dislodgement, and creation of a large-diameter fistula tract for potential fistulojejunostomy. We report the first clinical experience with UTDC for necrotizing pancreatitis. METHODS: From 2011 to 2014, all patients undergoing UTDC for necrotizing pancreatitis at our institution were identified. Clinical variables including patient, disease, and intervention-specific characteristics as well as long-term outcomes populated our dataset. RESULTS: Twenty-two patients underwent UTDC for necrotizing pancreatitis; the median follow-up was 10.2 months. Necrotizing pancreatitis was most commonly owing to gallstones (n = 9; 41%), idiopathic disease (n = 5; 23%), and alcohol abuse (n = 4; 18%). During the course of UTDC and definitive operative therapy (when required), patients had median hospital stays of 31 days, 6 interventional radiology procedures, and 6 CT scans. Operative intervention was not necessary in 9 patients (41%). Among the other 13 patients, 4 patients underwent distal pancreatectomy/splenectomy, 8 had a fistulojejunostomy performed, and 1 underwent both procedures. CONCLUSION: UTDC for necrotizing pancreatitis patients is associated with effective drainage and low morbidity/hospital resource utilization. With skilled interventional radiologists and multidisciplinary coordination, this technique is a valuable means of minimizing morbidity for patients with necrotizing pancreatitis. PMID- 26271526 TI - A urologist's contemporary guide to penile cancer. AB - Few urologists deal with penile cancer on a daily basis. Owing to the rarity of the disease and its diversity in presentation, clinical experience accumulates slowly and new paradigms spread sporadically. This review provides a concise update on the background, clinical features and multidisciplinary management strategies of penile cancer. The evidence base of penile cancer management recommendations is devoid of randomized controlled trials and relies mainly on retrospective cohort studies from single institutions. In recent years, international multicentre collaboration has increased the quality of evidence. Larger study cohorts allow researchers to engage in subgroup analysis of patients with poor prognosis, of which the literature so far has been scarce. Comprehensive evidence-based guidelines are available through the European Association of Urology. This review highlights the importance of early and minimally invasive regional lymph-node staging of all patients of stage T1G2 or higher, and underlines the therapeutic potential of inguinal lymph-node dissection in lymph-node positive patients. A discussion of the oncological safety of current trends towards more phallus-sparing treatment techniques emphasizes the importance of proper case selection, thorough patient information, consequent follow-up and the possibility of a reconstructive procedure after organ-sparing ablative penile surgery. The aetiological role of human papilloma virus (HPV) is touched upon and the evidence for circumcision and HPV vaccination of boys is briefly weighed. The value of multidisciplinary treatment of advanced penile cancer is underlined and the role of chemotherapy, radiotherapy and radiochemotherapy is discussed. Finally, the perspectives for hybrid tracer sentinel node, robot-assisted lymph-node surgery and targeted therapies are addressed. PMID- 26271527 TI - Circulating concentrations of vitamin E isomers: Association with bone turnover and arterial stiffness in post-menopausal women. AB - The effects of vitamin E on cardiovascular and bone health are conflicting with beneficial and detrimental findings reported. To investigate this further, we carried out a cross-sectional study to determine the relationship between circulating concentrations of the 2 vitamin E isomers, alpha- and gamma tocopherol (TP) with bone turnover and arterial stiffness. Two hundred and seventy eight post-menopausal women with mean age [SD] 60.9 [6.0] years were studied. Fasting serum alpha-TP and gamma-TP, bone turnover markers; procollagen type 1 amino-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX), parathyroid hormone (PTH), total cholesterol (TC) and triglycerides (TG) were measured. Pulse wave velocity (PWV) and central augmentation index (AI) as markers of arterial stiffness were also determined. A positive correlation was observed between alpha-TP and gamma-TP (r=0.14, p=0.022). A significant negative association between alpha-TP and P1NP only was seen in multiple linear regression analysis following adjustment for serum TC and TG (p=0.016). In a full multi-linear regression model, following correction for age, years since menopause, smoking habits, alcohol intake, use of calcium supplements, BMI, PTH, serum calcium, and estimated glomerular filtration rate (eGFR), the association between alpha-TP and P1NP remained significant (p=0.011). We did not observe any significant association between gamma-TP or alpha-TP/gamma TP ratio with P1NP or CTX. P1NP was significantly lower in subjects with alpha-TP concentrations of >30 MUmol/L (alpha-TP >30 MUmol/L; P1NP: 57.5 [20.7], alpha TP<30 MUmol/L; P1NP: 65.7 [24.9] MUg/L, p=0.005). PWV was significantly associated with alpha-TP/gamma-TP ratio (p=0.04) but not with serum alpha-TP or gamma-TP in a full multi-linear regression model adjusting for serum lipids, age, and blood pressure. The data suggest that high serum concentrations of alpha-TP may have a negative effect on bone formation. The balance of alpha-TP and gamma TP may be important in maintaining arterial compliance. Longitudinal studies are needed to investigate the impact of the vitamin E isomers on bone and cardiovascular health. PMID- 26271528 TI - Incisional metastasis from lung cancer after transcervical extended mediastinal lymphadenectomy. PMID- 26271529 TI - National consensus on the diagnosis, risk stratification and treatment of patients with pulmonary embolism: An update. PMID- 26271531 TI - A diagnostic algorithm for Parkinson's disease: what next? PMID- 26271533 TI - Genetically Encoded Voltage Indicators: Mapping Cardiac Electrical Activity Under a New Light. PMID- 26271535 TI - AntimiR-34a to Enhance Cardiac Repair After Ischemic Injury. PMID- 26271534 TI - Peering Into the Cardiomyocyte Nuclear Epigenetic State. PMID- 26271537 TI - Correction. PMID- 26271536 TI - Alloantibodies and Allograft Arteriosclerosis: Accelerated Adversity Ahead? PMID- 26271538 TI - Variations in Phase and Amplitude of Rhythmic Clock Gene Expression across Prefrontal Cortex, Hippocampus, Amygdala, and Hypothalamic Paraventricular and Suprachiasmatic Nuclei of Male and Female Rats. AB - The molecular circadian clock is a self-regulating transcription/translation cycle of positive (Bmal1, Clock/Npas2) and negative (Per1,2,3, Cry1,2) regulatory components. While the molecular clock has been well characterized in the body's master circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN), only a few studies have examined both the positive and negative clock components in extra-SCN brain tissue. Furthermore, there has yet to be a direct comparison of male and female clock gene expression in the brain. This comparison is warranted, as there are sex differences in circadian functioning and disorders associated with disrupted clock gene expression. This study examined basal clock gene expression (Per1, Per2, Bmal1 mRNA) in the SCN, prefrontal cortex (PFC), rostral agranular insula, hypothalamic paraventricular nucleus (PVN), amygdala, and hippocampus of male and female rats at 4-h intervals throughout a 12:12 h light:dark cycle. There was a significant rhythm of Per1, Per2, and Bmal1 in the SCN, PFC, insula, PVN, subregions of the hippocampus, and amygdala with a 24-h period, suggesting the importance of an oscillating molecular clock in extra-SCN brain regions. There were 3 distinct clock gene expression profiles across the brain regions, indicative of diversity among brain clocks. Although, generally, the clock gene expression profiles were similar between male and female rats, there were some sex differences in the robustness of clock gene expression (e.g., females had fewer robust rhythms in the medial PFC, more robust rhythms in the hippocampus, and a greater mesor in the medial amygdala). Furthermore, females with a regular estrous cycle had attenuated aggregate rhythms in clock gene expression in the PFC compared with noncycling females. This suggests that gonadal hormones may modulate the expression of the molecular clock. PMID- 26271532 TI - Diagnosis of Parkinson's disease on the basis of clinical and genetic classification: a population-based modelling study. AB - BACKGROUND: Accurate diagnosis and early detection of complex diseases, such as Parkinson's disease, has the potential to be of great benefit for researchers and clinical practice. We aimed to create a non-invasive, accurate classification model for the diagnosis of Parkinson's disease, which could serve as a basis for future disease prediction studies in longitudinal cohorts. METHODS: We developed a model for disease classification using data from the Parkinson's Progression Marker Initiative (PPMI) study for 367 patients with Parkinson's disease and phenotypically typical imaging data and 165 controls without neurological disease. Olfactory function, genetic risk, family history of Parkinson's disease, age, and gender were algorithmically selected by stepwise logistic regression as significant contributors to our classifying model. We then tested the model with data from 825 patients with Parkinson's disease and 261 controls from five independent cohorts with varying recruitment strategies and designs: the Parkinson's Disease Biomarkers Program (PDBP), the Parkinson's Associated Risk Study (PARS), 23andMe, the Longitudinal and Biomarker Study in PD (LABS-PD), and the Morris K Udall Parkinson's Disease Research Center of Excellence cohort (Penn Udall). Additionally, we used our model to investigate patients who had imaging scans without evidence of dopaminergic deficit (SWEDD). FINDINGS: In the population from PPMI, our initial model correctly distinguished patients with Parkinson's disease from controls at an area under the curve (AUC) of 0.923 (95% CI 0.900-0.946) with high sensitivity (0.834, 95% CI 0.711-0.883) and specificity (0.903, 95% CI 0.824-0.946) at its optimum AUC threshold (0.655). All Hosmer Lemeshow simulations suggested that when parsed into random subgroups, the subgroup data matched that of the overall cohort. External validation showed good classification of Parkinson's disease, with AUCs of 0.894 (95% CI 0.867-0.921) in the PDBP cohort, 0.998 (0.992-1.000) in PARS, 0.955 (no 95% CI available) in 23andMe, 0.929 (0.896-0.962) in LABS-PD, and 0.939 (0.891-0.986) in the Penn Udall cohort. Four of 17 SWEDD participants who our model classified as having Parkinson's disease converted to Parkinson's disease within 1 year, whereas only one of 38 SWEDD participants who were not classified as having Parkinson's disease underwent conversion (test of proportions, p=0.003). INTERPRETATION: Our model provides a potential new approach to distinguish participants with Parkinson's disease from controls. If the model can also identify individuals with prodromal or preclinical Parkinson's disease in prospective cohorts, it could facilitate identification of biomarkers and interventions. FUNDING: National Institute on Aging, National Institute of Neurological Disorders and Stroke, and the Michael J Fox Foundation. PMID- 26271539 TI - Longitudinal Study of Changes in Daily Activity Rhythms over the Lifespan in Individual Male and Female C57BL/6J Mice. AB - Mice are used widely for research on circadian, molecular and other processes; however, little is known of circadian age- and, particularly, sex-related changes that occur over the entire lifespan of this species. To shed light on this question, the authors used a longitudinal design for the first continuous actogram measurements of general circadian locomotor activity rhythms unperturbed by photocycle or other experimental manipulations over the lifespan in male and female C57BL/6J mice. These weaning-to-death actograms are the most inclusive undertaken to date. Comparisons of circadian parameters (phase angle of entrainment, length of daily activity, bout length/intensity) were made among 4 life stages (adolescence, adult, middle age, and senescence). The present data reveal the progressive and sex-related changes in general locomotor activity pattern that occur throughout the lifespan. From the overall perspective of this study, there appears to be a need for wider age and sex representation in circadian research. PMID- 26271541 TI - Posterior Mini-Incision With Primary Total Hip Arthroplasty: A Nine to Ten Year Follow Up Study. AB - The question has been raised as to whether small incision surgery will compromise long term results of total hip arthroplasty. We report nine to ten years' outcome with posterior mini-incision. Radiographs were measured for component position, polyethylene wear, fixation, and osteolysis. Sixty-two of the original 86 patients (76 of 100 hips) were alive and available for study with 17 patients deceased (with known results) and seven (8%) lost to follow-up. The result was rated as excellent in 70 of 75 remaining hips (93%). Eighty-nine of 93 hips (96%) with known results had the original implants. Radiographically, wear was a mean 0.015 +/- 0.009 mm/year, and no hip had impending failure. There were four revisions, 2 for dislocation, 1 for fracture, and 1 for loose cup. PMID- 26271540 TI - The Effect of Subluxation of Articulating Antibiotic Spacers on Bone Defects and Degree of Constraint in Revision Knee Arthroplasty. AB - This study investigated whether subluxation of articulating antibiotic spacers is associated with the bone defects found and constraint required when re-implanting the knee arthroplasty components. Staged revisions for infections of primary total knee arthroplasties between 2004 and 2012 were examined. Radiographic sagittal and coronal subluxations of 72 knees were measured prior to second stage revision. Coronal subluxation was found to be associated with increased requirement for constrained knee systems (P<0.035). Sagittal subluxation was associated with greater tibia bone defects (P<0.037). Careful surgical technique and monitoring of articulating spacers should be done to avoid subluxation after stage 1 revision. If subluxation of the articulating spacer is present, constrained revision knee systems as well as augments should be available at time of re-implantation. PMID- 26271542 TI - The Influence of Hip Rotation on Femoral Offset Following Short Stem Total Hip Arthroplasty. AB - Short stem total hip arthroplasty (THA) is thought to be an advantageous surgical option for young patients. Femoral offset has been identified as an important factor for clinical outcome of THA. However, little is known on functional implications of femoral offset after short stem THA. Importantly, hip rotation influences the projected femoral offset and may lead to significant underestimation. Therefore, a novel method to identify and account for hip rotation was applied to a prospectively enrolled series of 37 patients (48 radiographs) undergoing short stem THA. Repeated measurements were performed and intraobserver and interobserver reliability was assessed and femoral offset was corrected for rotation. Based on this study, rotation-correction of femoral offset is of highest relevance for the correct interpretation in future studies. PMID- 26271543 TI - Determining the True Cost to Deliver Total Hip and Knee Arthroplasty Over the Full Cycle of Care: Preparing for Bundling and Reference-Based Pricing. AB - The Affordable Care Act accelerates health care providers' need to prepare for new care delivery platforms and payment models such as bundling and reference based pricing (RBP). Thriving in this environment will be difficult without knowing the true cost of care delivery at the level of the clinical condition over the full cycle of care. We describe a project in which we identified true costs for both total hip and total knee arthroplasty. With the same tool, we identified cost drivers in each segment of care delivery and collected patient experience information. Combining cost and experience information with outcomes data we already collect allows us to drive costs down while protecting outcomes and experiences, and compete successfully in bundling and RBP programs. PMID- 26271544 TI - The burden of acute myocardial infarction after a regional cardiovascular center project in Korea. AB - OBJECTIVE: The aim of this study was to examine the impact of a government directed regional cardiovascular center (RCVC) project on the length of stay (LOS) and medical costs due to acute myocardial infarction (AMI). DESIGN: A retrospective claim data review. SETTING: Forty hospitals including four RCVCs in Korea. PARTICIPANTS: A total of 1469 AMI patients who visited a RCVC in two regions between February 2009 and December 2011. INTERVENTIONS: RCVC project has been fostering specialized center by region for management of cardiovascular disease. It has built a system that could receive intensive care quickly within 3 h when disease occurred. MAIN OUTCOME MEASURES: Changes in the LOS and cost were evaluated using the difference-in-differences (DIDs) method combined with propensity score matching (1:1) and multilevel analysis with adjustment for patient's and institutional factors. RESULTS: The net effect of RCVC project implementation showed decline of LOS (-0.71 days) and total medical costs (-797 US dollars) by DID. After the RCVC project, the LOS for patients with AMI hospitalized in a RCVC was decreased by 8.9% (beta = -0.094, P = 0.041) compared with patients hospitalized in a hospital not designed as a RCVC. Compared with costs before the RCVC project, they were decreased by 11.5% (beta = -0.122, P = 0.004). CONCLUSIONS: We provided evidence regarding the change in the societal burden due to AMI after regionalization. Although there was a reduction of LOS and direct medical costs reported in limited number of regionalized hospitals, in the long term we can anticipate an expanding impact in all regionalized hospitals. PMID- 26271545 TI - Differences between nurse- and physician-assessed ICU characteristics using a standardized survey. AB - OBJECTIVE: Surveys are often used to assess intensive care unit (ICU) organizational characteristics for quality improvement. Typically these surveys target ICU nurse managers and/or physician directors. However, it is unclear whether these providers' assessments differ. We sought to determine whether differences existed in nurse- and physician-assessed ICU characteristics using a standardized survey. DESIGN: We administered a previously developed survey to nurse managers and medical directors in adult ICUs within a single healthcare system in 2013. The survey asked about interprofessional staffing and evidence based protocols. We examined differences between nurse managers' and medical directors' responses using McNemar's test and assessed concordance using the kappa statistic. SETTING: Twenty-three ICUs in 10 hospitals in Southwestern Pennsylvania. RESULTS: Sixteen (69%) were specialty ICUs. The median number of ICU beds was 34. Concordance was moderate for high- vs. low-intensity physician staffing (kappa = 0.60) and almost perfect on questions related to interprofessional staffing (kappa = 0.83 nurse practitioners/physician assistants; 1.0 respiratory therapists; 0.83 physical therapists). However, concordance was slight to fair with regard to the presence of these providers on rounds (kappa = 0.20-0.21) and poor to slight for protocols for liberation from mechanical ventilation (kappa = 0.19), sedation (kappa = -0.03) and central line insertion (kappa = -0.03). CONCLUSIONS: Despite a standardized survey, we found substantial disagreement on ICU characteristics when assessed by the nurse manager or physician director. This study raises questions about the use of surveys to examine ICU organizational characteristics and suggests that differences in nurse managers' and medical directors' assessments could be helpful in guiding future ICU quality improvement projects. PMID- 26271546 TI - Synthetic polynucleotides as endosomolytic agents and bioenergy sources. AB - Nucleotides (NTs), such as adenosine triphosphate (ATP) and guanosine triphosphate (GTP), are signaling and bioenergy molecules to mediate a range of cellular pathways. We recently reported their significant endosomolytic activity. To evaluate whether polymeric NTs keep endosomolytic and bioenergetic functions of NTs in drug delivery and cell survival, NTs were polymerized by a coupling reaction to form polynucleotides (pNTs: pATP and pGTP) with their molecular weights around 500kDa. The cellular toxicity, indicated by IC50, of pNT was as low as that of corresponding monomeric NT. pNTs were degraded by an intracellular enzyme, alkaline phosphatase. Introduction of pNTs in a polycation-gene complex (polyplex) enhanced the extent of gene expression in cancerous, non-cancerous, and stem cells, up to 1500-fold higher than that of pNT-free polyplex. In addition, cells stored in a pATP solution resulted in a significantly higher survival rate (e.g., up to 20% increase) when exposed to low temperatures than pATP-free solution. The presence of pNT in polyplexes prevented the reduction of transfection efficiency induced by a low temperature. The findings in this study suggest that endosomolytic and bioenergetic pNTs serve as a non-toxic gene carrier component and protect cells from a cold shock or energy depletion. PMID- 26271547 TI - BCL2-like 11 intron 2 deletion polymorphism is not associated with non-small cell lung cancer risk and prognosis. AB - OBJECTIVES: BCL2-Like 11(BIM), which encodes a BH3-only protein, is a major pro apoptotic molecule that facilitates cell death. We hypothesized that a BIM intron 2 deletion polymorphism increases lung cancer risk and predicts poor prognosis in non-small lung cancer (NSCLC) patients. MATERIALS AND METHODS: We prospectively recruited 450 lung cancer patients and 1:1 age, sex, and smoking status matched control subjects from February 2013 to April 2014 among patients treated at Severance, Gangnam Severance, and Chonnam Hwasoon Hospital. The presence of a 2903-bp genomic DNA deletion polymorphism of intron 2 of BIM was analyzed by PCR and validated by sequencing. Odds ratios were calculated by chi-square tests and survival analysis with Kaplan-Meier estimation. RESULTS AND CONCLUSION: Sixty nine out of 450 (15.3%) lung cancer patients carried the BIM deletion polymorphism, while 66 out of 450 (14.7%) control subjects carried the BIM deletion polymorphism, with an odds ratio of for lung cancer of 1.054 (95% CI; 0.731-1.519). We categorized 406 NSCLC patients according to the presence of the polymorphism and found that there were no statistically significant differences in age, sex, histologic type, or stage between subjects with and without the deletion polymorphism. The BIM deletion polymorphism did not influence overall survival (OS) or progression free survival (PFS) in our sample (OS; 37.6 vs 34.4 months (P=0.759), PFS; 49.6 vs 26.0 months (P=0.434)). These findings indicate that the BIM deletion polymorphism is common in Korean NSCLC patients but does not significantly affect the intrinsic biologic function of BH3-only protein. Furthermore, the BIM deletion polymorphism did not predict clinical outcomes in patients with NSCLC. PMID- 26271548 TI - Authors' response--Risk of malignancy in pulmonary nodules: a validation study of four prediction models. PMID- 26271549 TI - Healthy Chinese with benign pancreatic hyperenzymemia. AB - Benign pancreatic hyperenzymemia, or Gullo's syndrome, is an uncommon syndrome characterized by a long-term increase of serum pancreatic enzyme in the absence of pancreatic diseases. It is primarily discovered incidentally and occurs in either sporadic or familial form. Herein, we report the first case of benign pancreatic hyperenzymemia in Taiwan. A 57-year-old Chinese male was incidentally noted with elevated serum amylase and lipase levels during a health check-up and was diagnosed with benign pancreatic hyperenzymemia using a series of image and serological tests. Although this is the first case of benign pancreatic hyperenzymemia in Taiwan, its prevalence may be underestimated due to the diagnostic difficulties. Correct diagnosis of this disease is important to avoid costly test duplication, unfounded anxieties, and multiple consultations. PMID- 26271550 TI - Regarding "Patient perception of physician reimbursement in elective shoulder surgery". PMID- 26271551 TI - Accuracy of magnetic resonance imaging in detecting biceps pathology in patients with rotator cuff disorders: comparison with arthroscopy. AB - BACKGROUND: There is limited information on the validity of magnetic resonance imaging (MRI) in detection of biceps disease. The purpose of this study was to examine the measurement properties of noncontrasted MRI in diagnosis of biceps disease using arthroscopic surgery as the "gold standard." MATERIALS AND METHODS: Prospectively collected surgical data of patients with impingement syndrome or rotator cuff tear, with biceps disease (study group) or without biceps disease (control group), were reviewed. MRI reports of radiologists with fellowship training in musculoskeletal imaging were retrospectively reviewed and compared with surgical findings. RESULTS: Data of 183 (130 study and 53 control) patients (73 women [40%], 110 men [60%]; mean age, 62 years [standard deviation, 9]) who had undergone arthroscopic rotator cuff-related surgery during a period of 11 years were used for analysis. Sensitivity and specificity of MRI for detection of full tears of the biceps tendon were 0.54 and 0.98, respectively. Sensitivity and specificity were 0.27 and 0.86 for partial tears of the biceps tendon, respectively. For biceps subluxation or dislocation, sensitivity was 1.00 and specificity was 0.83. The areas under the receiver operating characteristic curves, which quantify the overall accuracy of the tests, were 0.57, 0.75, and 0.92 for partial tear, full tear, and instability of the biceps tendon, respectively. CONCLUSIONS: Noncontrasted MRI has a low sensitivity and high specificity for detection of full-thickness tears of the biceps tendon. It is highly sensitive for diagnosis of instability of the long head of the biceps. However, its usefulness for diagnosis of partial tears of the biceps tendon remains limited. PMID- 26271553 TI - A Rapid Assessment Study on the Implementation of a Core Set of Interventions to Improve Cardiovascular Health in Latin America and the Caribbean. PMID- 26271552 TI - Opportunistic Screening for CVD Risk Factors: The Dubai Shopping for Cardiovascular Risk Study (DISCOVERY). AB - BACKGROUND: Comprehensive cardiovascular disease risk factor (CVDRF) screening programs are limited in the developing world. Simplifying screening can increase its utility. OBJECTIVES: The present study aims to estimate the burden of CVDRF in volunteers and the yield of newly discovered CVDRF comparing different sites and nationalities using this screening method. METHODS: Voluntary point-of-care CVDRF screening was conducted in 4 shopping malls, 9 health care facilities, and 3 labor camps in 5 cities in the United Arab Emirates. Follow-up for newly diagnosed diabetes mellitus, hypertension, and dyslipidemia was made 1 month after screening to inquire about physician consultation, confirmation of diagnosis, and lifestyle changes. RESULTS: A total of 4,128 subjects were screened (43% at malls, 36% at health care facilities, and 22% at labor camps). Subjects were relatively young (38 +/- 11 years), predominantly male (75%), and of diverse nationalities (United Arab Emirates: 7%, other Arabs: 10%, South Asians: 74%, other Asians: 5%, and other nationalities: 5%). CVDRF were frequent (diabetes mellitus: 32%, hypertension: 31%, dyslipidemia: 69%, current smokers: 21%, obesity: 20%, and central obesity: 24%). Most subjects (85%) had >=1 CVDRF, and many (17%) had >=3 CVDRF. A new diagnosis of diabetes mellitus, hypertension, or dyslipidemia was uncovered in 61.5%, with the highest yield (74.0%) in labor camps. At follow-up of those with new CVDRF, positive lifestyle changes were reported in 60%, but only 33% had consulted a doctor; of these, diagnosis was confirmed in 63% for diabetes mellitus, 93% for hypertension, and 87% for dyslipidemia. CONCLUSIONS: In this relatively young and ethnically diverse cohort, CVDRF burden and yield of screening was high. Screening in these settings is pertinent and can be simplified. PMID- 26271555 TI - Clinical application of WHF-MOGE(S) classification for hypertrophic cardiomyopathy. AB - BACKGROUND: Recently, a new MOGE(S) (Morphofunctional, Organ involvement, Genetics, Etiology of details of the genetic disease or underlying cause, and functional Status) genotype to phenotype nosology system for classification of cardiomyopathies was proposed, but its clinical use has not been described. OBJECTIVES: This study presents the comprehensive geno-phenotypic evaluation of hypertrophic cardiomyopathy (HCM) patients by employing the newly proposed World Heart Federation classification of cardiomyopathies - the MOGE(S) classification. METHODS: From January 2011 to March 2014, 254 patients were evaluated (190 probands and 64 family members). Of those, 181 were HCM phenotype-positive probands, and 54.7% were male patients. Mean maximal left ventricular thickness was 2.2 +/- 0.6 cm, with >2.5 cm thickness seen in 21.5% of patients. Obstructive HCM was present in 66.3% of patients, with an average peak gradient of 57.1 +/- 47.2. Detailed clinical, imaging, and follow-up data were analyzed. Gene testing was performed in 129 patients (67.9%), and they were categorized into gene positive (MHOHGADEG+) and gene-negative (MHOHGADEG-) groups based on the MOGE(S) classification. RESULTS: MHOHGADEG+ patients were younger at time of diagnosis, more likely to be female, more likely to have ventricular tachycardia and a family history of HCM or sudden death, had lower peak gradients, and were more likely to have sudden death risk factors. CONCLUSIONS: In addition to employing genotype-to-phenotype nosology to describe HCM, we propose a modification to the current MOGE(S) classification for HCM based on the presence or absence of obstruction and location of hypertrophy within the morphology. PMID- 26271554 TI - DS-Connect: A Promising Tool to Improve Lives and Engage Down Syndrome Communities Worldwide. AB - Down syndrome (DS) is the most common genetic cause of intellectual and developmental disabilities in the United States with an estimated birth prevalence of 1:691 births; however, worldwide estimates of the number of individuals with intellectual and developmental disabilities, including DS, remain speculative. Little is known about the global health impact of DS, such as heart defects, gastrointestinal malformations, and other medical and behavioral issues. Further research is needed to develop the next generation of novel therapies and compounds aimed at improving cognition, reducing dementia, and mitigating other manifestations of DS. To address these challenges, the National Institutes of Health has created the first web-based, voluntary registry and data resource called DS-Connect: The Down Syndrome Registry to collect demographic and health information about individuals with DS. PMID- 26271557 TI - Canadian trends in filicide by gender of the accused, 1961-2011. AB - This paper provides a comprehensive historical and contemporary picture of filicide in Canada for more than half a century. Focusing on 1,612 children under age 18 that were killed by their parents between 1961 and 2011, regional and temporal trends in the gender of accused are examined as well as differences in maternal and paternal filicides by the gender and age of the victim, the age and marital status of the accused, type of parental relationship, cause of death, motive, history of family violence, and clearance status. Results show that there are significant differences in filicides by mothers and fathers. Five possible emerging trends were identified: an increasing gender gap in accused, increasing presence of relationship breakdown, growing number of cases involving stepfathers and a prior history of family violence, and declines in accused who committed suicide. Implications of these trends for interventions and prevention are discussed and future research priorities highlighted. PMID- 26271556 TI - Longitudinal examination of peer and partner influences on gender-specific pathways from child abuse to adult crime. AB - Research provides increasing evidence of the association of child abuse with adult antisocial behavior. However, less is known about the developmental pathways that underlie this association. Building on the life course model of antisocial behavior, the present study examined possible developmental pathways linking various forms of child abuse (physical, emotional, sexual) to adult antisocial behavior. These pathways include child and adolescent antisocial behavior, as well as adulthood measures of partner risk taking, warmth, and antisocial peer influences. Data are from the Lehigh Longitudinal Study, a prospective longitudinal study examining long-term developmental outcomes subsequent to child maltreatment. Participant families in the Lehigh Longitudinal Study were followed from preschool age into adulthood. Analyses of gender differences addressed the consistency of path coefficients across genders. Results for 297 adult participants followed from early childhood showed that, for both genders, physical and emotional child abuse predicted adult crime indirectly through child and adolescent antisocial behavior, as well as adult partner and antisocial peer influences. However, for females, having an antisocial partner predicted an affiliation with antisocial peers, and that in turn predicted adult crime. For males, having an antisocial partner was associated with less partner warmth, which in turn predicted an affiliation with antisocial peers, itself a proximal predictor of adult crime. Sexual abuse also predicted adolescent antisocial behavior, but only for males, supporting what some have called "a delayed-onset pathway" for females, whereby the exposure to early risks produce much later developmental outcomes. PMID- 26271558 TI - [Treatment of upper esophageal sphincter achalasia as a little-known chapter of surgery]. AB - It is presented the results of survey and treatment of 32 patients with upper esophageal sphincter achalasia. In 29 of them achalasia was consequence of stroke in brain stem (Zakharchenko-Wallenberg syndrome). 28 patients were operated using P. Chodoch method in 7 cases and author's technique of myotomy with pharyngoesophageal junction plasty in 21 patients. Plastic myotomy gives excellent and good results in 81% of observations due to preservation of innervation of muscles providing function of epiglottis and pharyngeal constrictors. Severe condition of patients and elderly age are indication for P. Chodoch myotomy. PMID- 26271560 TI - [Possibilities of videothoracoscopy for penetrating thoracic injuries]. AB - It was analyzed the medical reports of 596 victims with thoracic injuries including 360 cases with following conventional therapeutic approach and 236 patients who underwent videothoracoscopy. We estimated condition severity in case of injuries of thoracic wall, lungs, pericardium and heart. Hemodynamic disorders were estimated according to Allgower-Burri shock index. Intrapleural bleeding was calculated using volume of hemothorax and time before injury and operation. Severity of physiological damages was determined using RTS criterion, anatomic- using ISS criterion. We estimated possibility for videothoracoscopy in patients with conventional therapeutic approach comparing severity of injuries, severity of condition in both groups and volume of surgery. Retrospective analysis revealed possibility of videothoracoscopy in 86.7% of victims with pulmonary injury, in 83.3% with bleeding at the muscular vessels of thoracic wall, in 40.3% with intercostal vessels injury, in 31.2% with heart injury, in 27.3% with damage of pericardium and in 18.8% with internal thoracic vessels injury. Our investigation revealed that videothoracoscopy may be used more widely in case of thoracic injury. PMID- 26271559 TI - [Risk factors of suppurative complications in case of thoracic injury]. AB - It was performed retrospective analysis of 463 cases of suppurative thoracic complications after injury (232) and closed thoracic trauma (231) for 20-year period. Incidence of purulent complications was 3.2% and 1.6% in case of injury and closed thoracic trauma respectively including pleural empyema in 1.5 and 1.3%, pulmonary abscess in 0.3 and 0.4%, mediastinitis in 0.35 and 0.12%, pericarditis in 1.5 and 0.26%, osteomyelitis in 0.4 and 0.18% respectively. Factors preceding suppurative complications in case of injuries and closed trauma have been considered as predictors. Multivariant regression analysis established significant risk factors of suppurative thoracic complications. Clotted hemothorax, mediastinal hemorrhage, heart injury, late appeal for medical assistance and mechanical ventilation over 5 days were identified irrespective of character of trauma. In case of thoracic injury there were damage of osteochondrous frame, hollow thoracic and abdominal organs, gunshot wound of lung, delirium and injuries severity over 20 scores according to ISS scale. Pulmonary bleeding, sternal fracture and Glasgow Coma Scale rate<12 scores were identified as risk factors in case of closed trauma. PMID- 26271561 TI - [Liver tissue regeneration under the influence of cryoprecipitate and alloplant]. AB - AIM: To study the effectiveness and impact of cryoprecipitate and alloplant on regeneration of liver tissue in patients with cirrhosis. MATERIAL AND METHODS: 114 patients with liver cirrhosis have been treated at the Department of Faculty Surgery of I.M. Sechenov First Moscow State Medical University from 2007 to 2014. Cryoprecipitate and alloplant were injected into cirrhotic liver tissue in the first (72 patients) and second (42 patients) groups under ultrasound control respectively. Patients' age was 48.9+/-12.14 years (range 18-75). There were 66 men (58%) and 48 (42%) women. Mixed (toxic and viral) etiology of cirrhosis was observed in 40.3% of patients, viral--in 25.8%, toxic--in 34.2%. RESULTS: Minimally invasive treatment under ultrasound showed significant (p>0.05) positive dynamics of hepatocellular failure, cytolytic and cholestatic syndromes, hypersplenism in 3, 6 and 12 months after cryoprecipitate administration in most patients with cirrhosis Child-Pugh class A, B and C (group 1). Alloplant injected into hepatic tissue causes less regeneration of liver tissue. It improves clinical and laboratory parameters in patients with cirrhosis Child-Pugh classes A and B. In case of class C allopolant is not effective. PMID- 26271562 TI - [Endovascular treatment of post-traumatic arteriovenous fistulae]. AB - AIM: To summarize the experience of endovascular treatment of traumatic arteriovenous fistulae. MATERIAL AND METHODS: Endovascular interventions for arteriovenous fistulae of different locations were applied in 16 patients aged 19 to 83 years (mean 50.4+/-14.3) in A.V. Vishnevskiy Institute of Surgery from 2003 to 2014. Among causes there were stab wounds, gunshot wounds, blunt trauma, iatrogenic. Different endovascular methods including stenting with self-opening and balloon-expanding stent-grafts, embolic coils and occluders implantation were used. RESULTS: Pain syndrome, disorders of support function and trophic changes were observed in patients with arteriovenous fistulae more localized more distal than lower one third of the thigh. More proximally located arteriovenous fistulae regardless of their diameter resulted severe heart failure and portal hypertension. Angiographic and clinical success was achieved in 100% of cases. Manifestations of heart failure and portal hypertension disappeared in all patients after endovascular interventions. Also support function restored, pain and trophic disorders were cured. CONCLUSION: Arteriovenous fistulae regardless of their size, location and time of existence must be dissociated. Prolonged arteriovenous shunting leads to severe heart failure. Current technologies and tools used in endovascular interventions provide reliable dissociation of arteriovenous fistulae even in case of difficult anatomical features. PMID- 26271563 TI - [Robot-assisted and laparoscopic partial splenectomy for nonparasitic cysts]. AB - 21 patients with nonparasitic spleen cysts were operated. Robot-assisted (RA) interventions were applied in 10 cases, laparoscopic--in 11 patients. Men surgery duration was 124 minutes in case of RA-technique and 120 minutes if laparoscopy was used. Blood loss was significantly lower in the group of RA resection (p=0.035). There were no conversions of access in the group of RA-operations while in group of laparoscopy conversion has been required in 1 case. We did not observe complications in case of RA-surgeries. Laparoscopic method was associated with 2 complications (left-sided hydrothorax and fluid accumulation in resection area). Postoperative hospital-stay did not differ in both groups and was 7.1 and 6.4 room-nights in case of RA-interventions and laparoscopy respectively. There were no deaths. Indications for robot-assisted partial splenectomy for nonparasitic cysts include location of mass in upper pole or hilus of spleen, its diameter more than 8 cm, body mass index more than 30 and splenomegaly. Lower pole resection and splenectomy are more advisable using laparoscopic method. PMID- 26271564 TI - [Estimation of regional blood flow in reimplanted segments of upper extremity]. AB - AIM: To examine the state of regional circulation in replanted segment of upper limb and hand, to determine diagnostic and prognostic value of radionuclide scintigraphy. MATERIAL AND METHODS: The study included 26 patients who underwent replantation of upper extremity segments. The control group included 12 patients who underwent autologous transplantation of toes on hand. All patients underwent isotope scintigraphy, ultrasound Doppler and pulse oximetry. Groups were comparable by gender, age, severity of injury. RESULTS: Depending on postoperative course two groups were determined: with favorable (27 patients) and complicated postoperative period (11 patients). Two types of regional circulation were identified according to dynamic scintigraphy: prevalence of blood flow in operated limb (type 1); prevalence of blood flow in healthy limb, or equal volumetric blood flow in operated and healthy limbs (type 2). Favorable early postoperative period was associated with prevalence of blood flow in operated limb. Only in 2 (7.7%) patients patients in this group acute arterial thrombosis was diagnosed. At the same time thrombosis of microanastomosis occurred in 45.4% of cases in the second group what is 5.5 times higher than in the first group. CONCLUSION: Significant prevalence of blood flow in operated limb is favorable prognostic sign of the early postoperative period. On the other hand the identity of blood flow or prevalence of such in healthy limb predispose to acute vascular complications in replantate or autoplantate. Radionuclide scintigraphy provides detailed assessment of regional blood flow in operated limb. However clinical monitoring has leading role in diagnosis of acute circulatory disorders in replantate or autoplantate. PMID- 26271565 TI - [Infectious arthritis of sternoclavicular joint: surgical approach to the issue]. AB - AIM: To study the features of occurrence, diagnosis, clinical course of infectious arthritis of sternoclavicular joint, as well as to develop differentiated therapeutic tactics depending on the clinical form and stage of disease. MATERIAL AND METHODS: It was analyzed treatment of 18 patients with infectious arthritis of sternoclavicular joint aged 27 to 88 years who were hospitalized for the period 2008-2014. Acute or chronic forms were determined depending on clinical course and serous arthritis, para-articular phlegmon and osteoarthritis--according to nature of tissue damage. Hypothermia and blunt trauma were often preceded to onset of disease. Diabetes and drug addiction were present as comorbidities. Also disease as the variant of purulent metastasis in case of sepsis was noted. Bone scintigraphy, CT and magnetic resonance imaging are the most informative. RESULTS: Infectious arthritis of sternoclavicular joint often had hematogenous origin, and Staphylococcus aureus was the most common cause. At the stage of serous arthritis antibacterial therapy was effective. Incision and drainage were performed urgently in case of para-articular phlegmon. Sternoclavicular joint resection was performed usually in 2-3 months after subsidence of inflammation. PMID- 26271566 TI - [Endovascular interventions for acute ischemia of intestine]. AB - It is presented 5 clinical observations of acute ischemia of intestine in which different endovascular interventions including isolated superior mesenteric artery stenting, rheolytic and aspiration thrombectomy and combination of techniques were applied. Surgical success with blood flow restoration in superior mesenteric artery was achieved in 4 of 5 patients. 2 patients have required laparotomy and intestinal resection. In 1 case extent of resection was significantly reduced after previous endovascular thrombectomy. There were no deaths. It is concluded that endovascular interventions may be considered as independent method of treatment of patients with acute mesenteric ischemia. PMID- 26271568 TI - [Treatment of wound defects in patients with neuroischemic form of diabetic foot syndrome]. AB - AIM: Developing an algorithm of diagnosis and treatment of wound defects in patients with neuroischemic form of diabetic foot syndrome, study of the effectiveness of collagen implants in closing of wound defects. MATERIAL AND METHODS: The paper describes the diagnostic algorithm for patients with wound defects in neuroischemic form of DFS. Wound cleansing from areas of necrosis, purulent-fibrinous plaque, biofilm of the wound was conducted on the day of hospitalization using hydrosurgery ultrasonic cavitation. We propose the method of closing the wound defect with high-tech biomaterials based on type I collagen. RESULTS: Implantation of type I collagen increased the relative rate of wound healing, reduced the amount of high amputation, and significantly reduced the average time of patients' stay in hospitals and their transfer to outpatient treatment. CONCLUSIONS: 1. Patients with neuroischemic form of diabetic foot syndrome should be timely and promptly pass the diagnostic phase. 2. Ultrasonic debridement is most effective method of wound preparation before its closure. 3. The use of bioplastic material Collost in patients with neuroischemic form of diabetic foot syndrome increases the rate of wound healing that leads to decrease the average patient's stay in hospital and reduce high amputations. 4. The average patient's stay in hospital reduced up to 20% that decreases the treatment costs of such category of patients. PMID- 26271567 TI - [Treatment of diffuse peritonitis in children]. AB - THE PURPOSE OF THE STUDY: Improving the treatment of advanced peritonitis via use in therapy antihypoxant Reamberin and hepatoprotector Remaxol, nutritional support, sanitation laparoscopic abdominal cavity. SUBJECTS: A total of 232 children aged 1 to 15 years with generalized purulent peritonitis treated at the children's surgical departments of Samara from 2001 to 2014. A study group comprised 148 patients who used the optimized pathogenetic therapy. In the study group was allocated two groups: 64 patients in the pathogenetic therapy that used antihypoxant reamberin, and 84 children in the treatment of which reamberin and hepatoprotector remaxol. All the children of the main group received nutritional support (trophic feedings), used in the surgical treatment of abdominal laparoscopic sanitation. Comprehensive survey includes the study of the dynamics of the level of white blood cells, leukocyte index on Kalf-Caliph, erythrocyte sedimentation rate, temperature, total albumin concentration, transaminase levels. RESULTS: Comparison of the studied parameters in the study and control groups, showed a more rapid decrease in the symptoms and signs of intoxication (leukocytosis, LII, body temperature), relief of enteric disease, recovery of protein-synthetic function of the liver, a decrease of cytolytic and mesenchymal inflammatory syndrome in the study group, especially in the subgroup in which therapy was included remaxol. CONCLUSIONS: Optimization of treatment involving the application of the combined drugs--antihypoxant reamberin, hepatoprotector remaxol, nutritional support and implementation of laparoscopic abdominal sanitation led to improved results of therapy common purulent peritonitis in children. PMID- 26271570 TI - [Surgical treatment of postoperative suppurative sternomediastinitis]. PMID- 26271569 TI - [Surgical accesses to retroperitoneal organs and anatomic structures in case of abdominal trauma]. AB - It is presented the detailed description with illustrations of 3 surgical accesses which are used by authors to dissect retroperitoneal organs and anatomic structures in victims with closed trauma and abdominal injury. We reported clinical observations of successful use of developed accesses. PMID- 26271571 TI - [Giant basalioma of scalp with intracranial invasion]. PMID- 26271572 TI - [Surgical treatment of degenerative two-level stenosis in thoracic spine]. PMID- 26271573 TI - [Hydatid disease of the left hip]. PMID- 26271574 TI - Broccoli seed extract: Genotoxicity and subchronic toxicity studies. AB - Potential health benefits have been attributed to broccoli consumption. Hence, there is potential for use of broccoli seed extract (BSE) in food or for use as a dietary supplement. To assess the potential safety of a BSE product, three genotoxicity experiments, including an Ames, in vivo mouse micronucleus, and in vivo mouse sperm abnormality assay, were carried out. BSE was subject to an acute oral toxicity test and was evaluated in a 30-day feeding study in rats. BSE showed no mutagenic activity in the Ames assay and no evidence of genotoxic potential in the in vivo assays at doses up to 10 g/kg body weight (bw). The LD50 of BSE in rats was >10 g/kg bw/d. In the 30-day feeding study, in which BSE was administered in the diet to provide doses of 0, 0.3, 1.0, or 3.0 g/kg bw/d, no toxicological significant effects were noted on body weight, body weight gain, organ weights, or on the results of hematological, clinical chemistry and histopathological evaluations. The no-observed-adverse-effect level was considered to be 3.0 g/kg bw/d, the highest dose tested. Collectively, these results support the safe use of BSE as a food ingredient or product. PMID- 26271575 TI - Immunological and histopathological characterization of cutaneous candidiasis. AB - Chronic mucocutaneous candidiasis constitutes a heterogeneous group of syndromes, characterized by non-invasive infection of the skin, nails and mucosal membranes by the fungus Candida spp. Although symptoms are heterogeneous, in all cases there is a reduction in protective cytokines, favouring the development of disease. The normal role of cytokines in skin lesions is not well understood. The present study aimed to investigate the progression of disease, understand specific cellular and molecular components involved in immunity to Candida albicans and determine the balance between pro- and anti-inflammatory cytokines over the course of cutaneous infection in immunocompetent mice. BALB/c mice (five per group) were inoculated with 5 * 10(6)C. albicans pseudohyphae in the deep dermis of the paw and analysed over 1-14 days post-infection. The contralateral paws were used for negative controls. Haematoxylin and eosin staining of skin sections during C. albicans infection was performed to analyse structural modifications to the epidermis such as hyperplasia, and infiltration of neutrophils and fibroblasts in the dermis. The cytokine populations were determined by capture ELISA using popliteal lymph node tissue. Pro-inflammatory cytokines (IL-6, TNF-alpha, IL-12, IFN-gamma and IL-17) were detected at significant levels during the initial phase of cutaneous infection and correlated with the rapid elimination of C. albicans. Anti-inflammatory cytokines (IL-13, IL 4, IL-10 and transforming growth factor-beta) were detected on day 4 post infection, and prevented exacerbation of inflammation and participated in healing of lesions. Thus, a balance between pro- and anti-inflammatory cytokines was fundamental for the resolution of infection. Importantly, these findings broaden our understanding of the immune mechanisms involved in chronic cutaneous candidiasis. PMID- 26271576 TI - First report of Urosporidium sp., a haplosporidian hyperparasite infecting digenean trematode Parvatrema duboisi in Manila clam, Ruditapes philippinarum on the west coast of Korea. AB - In this study, we first report on the occurrence of Urosporidium sp., a haplosporidian hyperparasite infecting the trematode, Parvatrema duboisi, which parasitizes Manila clams, Ruditapes philippinarum on the west and south coasts of Korea. The larval P. duboisi infected by the sporocyst stage of Urosporidium sp. demonstrated numerous small yellowish spores in their tissues. The heavily infected metacercariae exhibited degenerate bodies and the larvae were often motionless. Clams heavily infected by the metacercariae of P. duboisi also displayed abnormal golden spots on the mantle tissue. In histology, different life stages of Urosporidium sp. could be identified, including the uni-nucleate, plasmodial, sporogonic stages and the acid fast mature spores released from the cyst. In scanning electron microscopy (SEM), the mature spore exhibited a semi circular rim around the apical end and the orifice was covered internally with a flap. Loop-like filaments ornamentation was also identified from Urosporidium sp. in SEM, suggesting that Urosporidium sp. found in this study is a new member in the genus. Prevalence of Urosporidium sp.-infected trematodes in this study ranged from 2.5% to 24.0% in April 2010 and the infection was observed from 8 sampling sites out of the 26 sites surveyed on the west and south coasts. PMID- 26271577 TI - Deletion of luxS further attenuates the virulence of the avian pathogenic Escherichia coli aroA mutant. AB - In this study, an aroA-deletion avian pathogenic Escherichia coli (APEC) mutant (strain DE17DeltaaroA) and aroA and luxS double deletion APEC mutant (strain DE17DeltaluxSDeltaaroA) were constructed from the APEC DE17 strain. The results showed that as compared to DE17DeltaaroA, the virulence of DE17DeltaluxSDeltaaroA was further attenuated by 200- and 31.7-fold, respectively, in ducklings based on the 50% lethal dose. The adherence and invasion abilities of DE17DeltaluxSDeltaaroA and DE17DeltaaroA were reduced by 36.5%/42.5% and 25.8%/29.3%, respectively, as compared to the wild-type strain DE17 (p < 0.05 and 0.01, respectively). Furthermore, in vivo studies showed that the bacterial loads of DE17DeltaluxSDeltaaroA were reduced by 8400- and 11,333-fold in the spleen and blood of infected birds, respectively, while those of DE17DeltaaroA were reduced by 743- and 1000-fold, respectively, as compared to the wild-type strain DE17. Histopathological analysis showed both that the mutants were associated with reduced pathological changes in the liver, spleen, and kidney of ducklings, and changes in DE17DeltaluxSDeltaaroA-infected ducklings were reduced to a greater degree than those infected with DE17DeltaaroA. Real-time polymerase chain reaction analysis further demonstrated that the mRNA levels of virulence-related genes (i.e., tsh, ompA, vat, iucD, pfs, fyuA, and fimC) were significantly decreased in DE17DeltaaroA, especially in DE17DeltaluxSDeltaaroA, as compared to DE17 (p < 0.05). In addition, the deletion of aroA or the double deletion of aroA and luxS reduced bacterial motility. To evaluate the potential use of DE17DeltaluxSDeltaaroA as a vaccine candidate, 50 7-day-old ducklings were divided randomly into five groups of ten each for the experiment. The results showed that the ducklings immunized with inactivated DE17, DE17DeltaluxS, DE17DeltaaroA, and DE17DeltaluxSDeltaaroA were 70.0%, 70.0%, 70.0, and 80.0% protected, respectively, after challenge with strain APEC DE17. The results of this study suggest that the double deletion of luxS and aroA attenuated APEC pathogenicity and DE17DeltaluxSDeltaaroA was more appropriate for development of a future vaccine against avian colibacillosis than DE17DeltaaroA. PMID- 26271578 TI - Increased Distance From the Tertiary Cardiac Center Is Associated With Worse 30 Day Outcomes After Cardiac Operations. AB - BACKGROUND: Numerous studies have examined the effect of geographic place of residence on access to cardiovascular care, but few have examined their effect on outcomes after cardiac operations. This study examined the effect of geographic place of residence on in-hospital and 30-day outcomes after cardiac operations. METHODS: We performed a retrospective analysis of all patients undergoing nonemergency cardiac operations at a single institution between April 2004 and March 2011. Geographic place of residence was defined as the driving distance from the patient's home to the tertiary cardiac care center divided into the following categories: 0 to 50 km, 50 to 100 km, 100 to 150 km, 150 to 200 km, 200 to 250 km, and more than 250 km. Multivariable logistic regression was used to determine the independent effect of driving distance on in-hospital and 30-day outcomes. RESULTS: The final study population included 4,493 patients, of whom 3,897 (86.7%) had 30-day follow-up. After adjusting for differences among patient groups, no consistent relationship existed between distance and in-hospital outcomes. However, increased distance beyond 100 km was significantly associated with a greater risk of adverse outcomes at 30 days (0 to 50 km: referent; 50 to 100 km: odds ratio, 1.16 [95% confidence interval, 0.83 to 1.62]; 100 to 150 km: 1.32 [1.05 to 1.65], 150 to 200 km: 1.68 [1.33 to 2.11], 200 to 250 km: 1.41 [1.06 to 1.88], and >250 km: 1.30 [1.04 to 1.63]). CONCLUSIONS: Patients who live at an increased distance from the tertiary cardiac care center are more likely to have worse 30-day outcomes after cardiac operations. Further study is required to determine the mechanisms underlying this relationship and how such inequalities may be minimized. PMID- 26271579 TI - Potential Impact of Modifiable Clinical Variables on Length of Stay After First Time Cardiac Surgery. AB - BACKGROUND: Recent financial challenges highlight the importance of accurate prediction of length of hospital stay (LOS). We assessed reliability of The Society of Thoracic Surgeons (STS) risk prediction for extended and shorter LOS and examined whether modifiable clinical variables are associated with LOS in first-time cardiac surgery patients. METHODS: Isolated aortic valve, mitral valve, and coronary artery bypass graft surgery patients since 2008 were included (n = 3,472). Multivariate regression was used to evaluate nonmodifiable and potentially modifiable (preoperative hematocrit, hemoglobin A1c, body mass index, current smoker, major perioperative morbidity, and blood product transfusion) predictors of LOS in days. RESULTS: Mean age was 63.9 +/- 11.2 years, 76% were males, and mean STS mortality risk was 1.9% +/- 3.2%. Median (interquartile range) LOS was 4 (3 to 6) days. Predicted STS risk was 6.2% +/- 7.1% for extended LOS (>14 days) and 48.3% +/- 20.2% for short LOS (<6 days). Extended LOS was observed in 5.2% of patients (observed versus expected, 0.84; p = 0.019). Observed short LOS was better than predicted (67.8%; observed versus expected, 1.40; p < 0.001). Inclusion of modifiable variables in the LOS prediction model was significant (p < 0.001). Significant modifiable predictors were lower hematocrit, higher hemoglobin A1c, major morbidity, and transfusion. Longer predicted LOS from the model correlated with longer actual LOS (rs = 0.63; p < 0.001). Applying the prediction equation from the model to a hypothetical average patient, predicted LOS was 4.6 days. CONCLUSIONS: The STS risk model was reliably predictive of short and extended LOS but did not allow prediction of exact LOS in days. Accounting for potentially modifiable clinical variables, such as low hematocrit and blood transfusion, especially in elective patients, should lead to shorter LOS, higher satisfaction, and reduced financial burden. PMID- 26271581 TI - Transcatheter and Surgical Aortic Valve Replacement in Dialysis Patients: A Propensity-Matched Comparison. AB - BACKGROUND: Transcatheter aortic valve replacement (TAVR) clinical trials in North America excluded patients on dialysis and, consequently, the outcomes of TAVR in dialysis-dependent patients remain unknown. METHODS: All Medicare fee-for service patients undergoing TAVR (n = 5,005) or surgical aortic valve replacement (SAVR) (n = 32,634) between January 1, 2011, and November 30, 2012, were identified using procedural codes collected by the Centers for Medicare & Medicaid Services. Dialysis status and comorbidities were identified using diagnosis codes present on arrival for TAVR hospitalization. Patients supported on dialysis who underwent TAVR (n = 224) were compared with non-dialysis patients who underwent TAVR as well as a propensity-matched group of contemporaneous dialysis patients who underwent SAVR (n = 194 pairs). RESULTS: The TAVR patients on dialysis were younger than non-dialysis TAVR patients (79.2 years vs 84.1 years; p < 0.01) but had higher prevalence of comorbidities. Dialysis TAVR patients had increased mortality at 30 days (13% vs 6%, p < 0.01) and significantly worse survival by Kaplan-Meier analysis. Multivariable regression found dialysis to be independently associated with worse survival (hazard ratio, 1.73; 95% confidence interval, 1.33% to 2.25%, p < 0.01) in TAVR patients. Propensity-matched dialysis SAVR and dialysis TAVR patients had no significant differences in demographic or risk factors. Matched dialysis TAVR patients had shorter length of stay (6 interquartile range, 4 to 10] vs 10 [IQR 7 to 18] days; p < 0.01) and comparable survival. CONCLUSIONS: TAVR in dialysis patients is associated with decreased survival compared with non-dialysis patients; however, it is comparable with SAVR in high risk dialysis patients based on a propensity matched comparison. PMID- 26271582 TI - Is Total Arch Replacement Associated With Worse Outcomes During Repair of Acute Type A Aortic Dissection? AB - BACKGROUND: As acute type A aortic dissection (ATAAD) remains a challenge, the extent of resection of the transverse arch remains debated during operative repair. The purpose of this study was to compare the outcomes of total arch repair versus ascending/proximal arch repair for ATAAD. METHODS: We retrospectively reviewed our aortic database of ATAAD between October 1999 and December 2014. Patients were divided into two groups: total arch repair versus proximal arch repair (hemiarch). Indications for arch replacement during ATAAD include aneurysm greater than 5 cm, complex arch tear, and arch rupture. Inhospital and long-term outcomes were compared between the two groups using univariate analysis and multiple logistic regression analysis. Survival was analyzed using Kaplan-Meier and log rank statistics, and assessment of risk factors for survival was conducted by Cox proportional hazards regression analysis. RESULTS: During the study period, we performed 489 repairs of ATAAD, 49 patients (10%) with total arch replacement and 440 patients (90%) with proximal arch replacement. Patients with total arch repair were older (62.4 +/- 13.4 years versus 57.9 +/- 14.8 years, p = 0.046) and had significantly increased retrograde aortic dissection, circulatory arrest, and retrograde cerebral perfusion times. The incidences of early mortality, stroke, and need for renal dialysis between the total arch and proximal arch group were not significantly different: 20.4% (10 of 49) versus 12.9% (57 of 440), 8.2% (4 of 49) versus 10.5% (46 of 440), and 27% (13 of 49) versus 17.6% (76 of 432), respectively. Late survival did not demonstrate a difference between groups. CONCLUSIONS: Acute type A aortic dissection remains a challenge associated with significant mortality and morbidity. When compared with a less aggressive resection, total arch replacement performed in an individualized fashion can be associated with acceptable early and late outcomes for ATAAD and was not associated with worse outcomes. PMID- 26271580 TI - Beating-Heart Versus Conventional On-Pump Coronary Artery Bypass Grafting: A Meta Analysis of Clinical Outcomes. AB - BACKGROUND: Beating-heart on-pump coronary artery bypass grafting (BH-ONCAB) offers a hybrid coronary revascularization technique that may confer the benefits of an "off-pump" operation while maintaining the hemodynamic stability and mechanical support of conventional on-pump CABG (C-ONCAB). This study aimed to identify whether BH-ONCAB confers a morbidity or mortality benefit over C-ONCAB in the immediate and midterm postoperative period. METHODS: A systematic literature review identified 13 studies incorporating 3,930 patients (937 BH ONCAB; 2,993 C-ONCAB) fulfilling our inclusion criteria. Outcomes were meta analyzed using random-effects modelling. Between-study heterogeneity was investigated through quality assessment, subgroup, and risk of bias analysis. RESULTS: No difference was seen in overall 30-day mortality (13 studies; odds ratio, 0.60; 95% confidence interval, 0.32 to 1.14; p = 0.12), or midterm survival (5 studies; hazard ratio, 0.65; 95% confidence interval, 0.22 to 1.88; p = 0.43) between BH-ONCAB and C-ONCAB. BH-ONCAB was associated with significantly fewer postoperative myocardial infarction events (odds ratio, 0.32; 95% confidence interval, 0.11 to 0.92; p = 0.03); however, no significant difference was observed in other postoperative morbidity outcomes. Intraoperatively, BH ONCAB resulted in significantly less intraaortic balloon pump use, shorter cardiopulmonary bypass time, and less blood loss. The number of anastomoses and vessels grafted were not significantly different between BH-ONCAB and C-ONCAB. CONCLUSIONS: BH-ONCAB is a safe and comparable alternative to C-ONCAB in terms of early mortality and late survival. Furthermore, BH-ONCAB may confer a particular advantage in preventing perioperative myocardial infarction and reducing overall blood loss. Future work should focus on larger matched studies and multicenter randomized controlled trials that risk-stratify patients according to preoperative ventricular function and renal insufficiency to allow us to optimize our surgical revascularization strategy in these high-risk patients. PMID- 26271583 TI - Nadir Oxygen Delivery on Bypass and Hypotension Increase Acute Kidney Injury Risk After Cardiac Operations. AB - BACKGROUND: Acute kidney injury (AKI) continues to complicate cardiac operations. We sought to determine whether nadir oxygen delivery (DO2) on cardiopulmonary bypass (CPB) was a risk factor for AKI while also accounting for other postoperative factors. METHODS: Using propensity scoring, we matched 85 patients who developed AKI after cardiac operations on CPB with 85 control patients who did not. We analyzed the following variables through midnight on postoperative day 1 (POD1): DO2, antibiotics, blood products and vasopressors (intraoperatively and postoperatively), and hemodynamic variables. RESULTS: Univariable analysis revealed AKI patients had lower nadir DO2 on CPB (208 vs 230 mL O2/min/m(2) body surface area, p = 0.03), lower intensive care unit admission blood pressure gradient across the kidney (mean arterial pressure minus central venous pressure; 60 vs 68 mm Hg; p < 0.001), a greater proportion of patients with mean arterial pressure of less than 60 mm Hg for more than 15 minutes in the postoperative period (70% vs 42%, p < 0.001), a greater chance of having a cardiac index of less than 2.2 (74% vs 49%, p = 0.02), and greater total vasopressor use through the end of POD1 (5.2 vs 2.3 mg, p = 0.002). On multivariable analysis, predictors of AKI were a DO2 on CPB of less than 225 mL O2/min/m(2) (odds ratio, 2.46; 95% confidence interval, 1.21 to 5.03; p = 0.01) and postoperative mean arterial pressure of less than 60 mm Hg for more than 15 minutes (odds ratio, 3.96; 95% confidence interval, 1.92 to 8.20; p < 0.001). An average postoperative pressor dose greater than 0.03 MUg/kg/min did not reach significance (odds ratio, 1.98; 95% confidence interval, 0.95 to 4.11; p = 0.07). CONCLUSIONS: Postoperative hypotension on POD0 or POD1 and low DO2 on CPB both independently increase the AKI risk in cardiac surgical patients. PMID- 26271584 TI - Midterm Outcome of Coronary Artery Bypass Grafting in Young Patients: A Multicenter Italian Study. AB - BACKGROUND: Myocardial revascularization in young patients should be durable enough to avoid new cardiovascular events or repeated revascularization procedures. The aim of this study was to evaluate the late outcomes of patients less than 50 years of age undergoing coronary artery bypass grafting (CABG) in comparison with older patients. METHODS: This study was a survival analysis of a pooled multicenter prospective cohort of patients who underwent CABG. RESULTS: Five percent of patients (572 of 11,087) were less than 50 years of age. The prevalence of female sex, pulmonary disease, diabetes, stroke, and extracardiac arteriopathy was lower compared with that in older patients. Left ventricular function was more well preserved in patients less than 50 years of age, but the prevalence of recent myocardial infarction and the need for emergency surgical intervention was significantly higher in young patients. Multiple propensity score-adjusted analysis showed that patients aged less than 50 years had a significantly lower risk of mortality, even when compared with the 50- to 59-year stratum. In the propensity score-matched population (544 pairs), patients less than 50 years of age had significantly better 7-year outcomes compared with patients aged 50 years or more: survival (95.6% versus 81.1%; p < 0.0001), freedom from stroke (97.4% versus 95.3%; p = 0.009), freedom from major adverse cardiac and cerebrovascular events (MACCE) (76.6% versus 63.9%; p = 0.002). Similar freedom from myocardial infarction (90.1% versus 90.1%; p = 0.68) and repeated revascularization (87.1% versus 87.2%; p = 0.65) was observed in patients less than 50 years of age and those older than 50 years. CONCLUSIONS: Patients less than 50 years of age undergoing CABG have an excellent outcome compared with elderly patients. These data indicate that despite its premature onset, coronary artery disease in young patients does not have a more aggressive course than that in older patients. PMID- 26271585 TI - Design of novel dispirooxindolopyrrolidine and dispirooxindolopyrrolothiazole derivatives as potential antitubercular agents. AB - With the aim to develop new potent antitubercular agents, a series of novel dispirooxindolopyrrolidines and dispirooxindolopyrrolothiazoles have been synthesized via a three-component 1,3-dipolar cycloaddition of (Z)-3 arylidenebenzofuran-2-ones, substituted isatin derivatives and alpha-aminoacids. The stereochemistry of the spiroadducts has been confirmed by an X-ray diffraction analysis. All the target heterocycles were evaluated for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv strain and the most active compounds were subjected to cytotoxicity studies against (RAW 264.7) cell lines. Among them, twelve compounds showed potent anti-tubercular activity with MIC ranging from 1.56 to 6.25 MUg/mL. In particular dispirooxindolopyrrolothiazole derivatives 5c and 5f were found to be the most active (MIC of 1.56 MUg/mL) with a good safety profile (27.53% and 20.74% at 50 MUM, respectively). This is the first report demonstrating the benzofuranone oxindole hybrids as potential antimycobacterial agents. PMID- 26271586 TI - Isolation and structure of vanitaracin A, a novel anti-hepatitis B virus compound from Talaromyces sp. AB - Two new tricyclic polyketides, vanitaracin A (1) and B (2), together with three novel compounds 3, 4 and 5, were isolated from a culture broth of a fungus, Talaromyces sp. The chemical structures of these compounds were determined from spectroscopic data (1D/2D NMR, MS and IR). The five isolated compounds were then tested for anti-hepatitis B virus (HBV) activity and vanitaracin A was found to exhibit an IC50 value of 10.5 MUM using a HBV-susceptible cell line. By contrast, the derivative 2 displayed weak anti-HBV action, which suggested that the substituents at C-9 in 1 are likely to be important for its antiviral activity. We believe the two vanitaracin derivatives constitute a new class of anti-HBV agents. PMID- 26271588 TI - Recent progress in the development of small-molecule glucagon receptor antagonists. AB - The endocrine hormone glucagon stimulates hepatic glucose output via its action at the glucagon receptor (GCGr) in the liver. In the diabetic state, dysregulation of glucagon secretion contributes to abnormally elevated hepatic glucose output. The inhibition of glucagon-induced hepatic glucose output via antagonism of the GCGr using small-molecule ligands is a promising mechanism for improving glycemic control in the diabetic state. Clinical data evaluating the therapeutic potential of small-molecule GCGr antagonists is currently emerging. Recently disclosed clinical data demonstrates the potential efficacy and possible therapeutic limitations of small-molecule GCGr antagonists. Recent pre-clinical work on the development of GCGr antagonists is also summarized. PMID- 26271589 TI - Vascular barrier protective effects of 3-N- or 3-O-cinnamoyl carbazole derivatives. AB - In this Letter, we investigated the barrier protective effects of 3-N-(MeO)n cinnamoyl carbazoles (BS 1; n=1, BS 2; n=2, BS 3; n=3) and 3-O-(MeO)3-cinnamoyl carbazole (BS 4) against high-mobility group box 1 (HMGB1)-mediated vascular disruptive responses in human umbilical vein endothelial cells (HUVECs) and in mice for the first time. Data showed that BS 2, BS 3, and BS 4, but not BS 1, inhibited HMGB1-mediated vascular disruptive responses and transendothelial migration of human neutrophils to HUVECs. BS 2, BS3, and BS 4 also suppressed HMGB1-induced hyperpermeability and leukocyte migration in mice. Interestingly, the barrier protective effects of BS 3 and BS 4 were better than those of BS 2. These results suggest that the number of methoxy groups substituted on the cinnamamide or cinnamate moiety of the 9H-3-carbazole derivative is an important pharmacophore for the barrier protective effects of these compounds. PMID- 26271587 TI - Discovery of selective N-[3-(1-methyl-piperidine-4-carbonyl)-phenyl]-benzamide based 5-HT1 F receptor agonists: Evolution from bicyclic to monocyclic cores. AB - Preclinical experiments and clinical observations suggest the potential effectiveness of selective 5-HT1F receptor agonists in migraine. Identifying compounds with enhanced selectivity is crucial to assess its therapeutic value. Replacement of the indole nucleus in 2 (LY334370) with a monocyclic phenyl ketone moiety generated potent and more selective 5-HT1F receptor agonists. Focused SAR studies around this central phenyl ring demonstrated that the electrostatic and steric interactions of the substituent with both the amide CONH group and the ketone CO group play pivotal roles in affecting the adopted conformation and thus the 5-HT1F receptor selectivity. Computational studies confirmed the observed results and provide a useful tool in the understanding of the conformational requirements for 5-HT1F receptor agonist activity and selectivity. Through this effort, the 2-F-phenyl and N-2-pyridyl series were also identified as potent and selective 5-HT1F receptor agonists. PMID- 26271590 TI - Microbiological and molecular epidemiological analyses of community-associated methicillin-resistant Staphylococcus aureus at a tertiary care hospital in Japan. AB - Molecular characterization of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is generally conducted referred to staphylococcal cassette chromosome mec (SCCmec) type IV or V. CA-MRSA is now a cause of concern since such strains have been isolated not only from individuals in a community but also from patients in healthcare settings. The aim of this study was to analyze microbiological and molecular epidemiological features of CA-MRSA strains at a Japanese tertiary care hospital using PCR based-open reading frame typing (POT). This technique allows for molecular classification into CA-MRSA (POT-CA) and hospital-associated (HA-) MRSA (POT-HA) with clonal discrimination. Clinical MRSA isolates obtained from consecutive patients between October 1, 2012 and September 30, 2013 at the hospital were analyzed in combination with the clinical definition for CA-MRSA by the Centers for Disease Control and Prevention and POT. Of 219 isolates (76 clonal groups), 64 (29.3%) were clinical-HA/POT-CA isolates (22 clonal groups). Some clones of them accumulated in this hospital and might be involved in nosocomial transmission. Virulent factors of the isolates were analyzed, and only one (1.6%) Panton-Valentine leukocidin gene positive isolate but no arginine catabolic mobile element genes positive isolate were found in clinical-HA/POT-CA. Additionally, clinical-HA/POT-CA isolates showed higher antimicrobial susceptibility than clinical-HA/POT-HA, especially to minocycline, doxycycline, and amikacin. The most frequent genotype of molecular CA-MRSA was multi-locus sequence type 5-SCCmecIV, previously not detected in Japan. Although CA-MRSA at this hospital showed low virulence and higher antimicrobial susceptibility, the risk of nosocomial infection from them should be recognized, requiring stricter infection control measures. PMID- 26271591 TI - Gene polymorphisms of mannose-binding lectin confer susceptibility to Pneumocystis pneumonia in HIV-infected patients. AB - BACKGROUND: Mannose-binding lectin (MBL) plays an important role in innate immunity. The aim of this study was to determine whether genetic variants of MBL confer susceptibility to Pneumocystis pneumonia (PCP) in patients with advanced human immunodeficiency virus (HIV) infections. OBJECTIVE: HIV patients (n = 53) having CD4 counts <200/MUL who were admitted to our hospital were analyzed. Of these 53 patients, 30 had PCP at admission, and 23 did not. Genotypes at six single nucleotide polymorphisms (SNP) in MBL2 gene and serum MBL levels were determined for each patient, and compared between patients with or without PCP. We also examined whether MBL enhances phagocytosis of macrophages against rat type Pneumocystis organism in vitro. RESULTS: Genotypes associated with low production of MBL were significantly more common in the PCP group than in the non PCP group (P = 0.049, odds ratio 2.17, 95% CI 1.02-4.63). Serum MBL levels were significantly higher in the non-PCP group (P = 0.039). Findings from in vitro experiments indicated that MBL act as a direct opsonin enhancing macrophage mediated phagocytosis of Pneumocystis organisms. CONCLUSION: Genetic variation of MBL production influences susceptibility to PCP in patients with advanced HIV infection, and can be regarded as a risk factor for PCP. PMID- 26271593 TI - Effective ATPase activity and moderate chaperonin-cochaperonin interaction are important for the functional single-ring chaperonin system. AB - Escherichia coli chaperonin GroEL and its cochaperonin GroES are essential for cell growth as they assist folding of cellular proteins. The double-ring assembly of GroEL is required for the chaperone function, and a single-ring variant GroEL(SR) is inactive with GroES. Mutations in GroEL(SR) (A92T, D115N, E191G, and A399T) have been shown to render GroEL(SR)-GroES functional, but the molecular mechanism of activation is unclear. Here we examined various biochemical properties of these functional GroEL(SR)-GroES variants, including ATP hydrolysis rate, chaperonin-cochaperonin interaction, and in vitro protein folding activity. We found that, unlike the diminished ATPase activity of the inactive GroEL(SR) GroES, all four single-ring variants hydrolyzed ATP at a level comparable to that of the double-ring GroEL-GroES. The chaperonin-cochaperonin interaction in these single-ring systems was weaker, by at least a 50-fold reduction, than the highly stable inactive GroEL(SR)-GroES. Strikingly, only GroEL(SR)D115N-GroES and GroEL(SR)A399T-GroES assisted folding of malate dehydrogenase (MDH), a commonly used folding substrate. These in vitro results are interesting considering that all four of the single-ring systems were able to substitute GroEL-GroES to support cell growth, suggesting that the precise action of chaperonin on MDH folding may not represent that on the intrinsic cellular substrates. Our findings that both effective ATP hydrolysis rate and moderate chaperonin-cochaperonin interaction are important factors for functional single-ring GroEL(SR)-GroES are reminiscent of the naturally occurring single-ring human mitochondrial chaperonin mtHsp60-mtHsp10. Differences in biochemical properties between the single- and double-ring chaperonin systems may be exploited in designing molecules for selective targeting. PMID- 26271594 TI - Key subdomains in the C-terminal of cerebral dopamine neurotrophic factor regulate the protein secretion. AB - Cerebral dopamine neurotrophic factor (CDNF) is a novel evolutionary conserved neurotrophic factor (NTF) which can protect and repairs dopamine neurons in animal models of Parkinson's disease. The crystal structure of CDNF is dominated by eight alpha-helices and the 3-dimensional structure of CDNF consists of an N terminal saposin-like domain and a C-terminal SAP-domain. In particular, the C terminal domain contains two critical motifs, a CXXC motif and a putative ER retention signal sequences (KTEL) at the C-terminus, which indicate that CDNF may be involved in endoplasmic reticulum (ER) stress. In this study, we found that disrupting helix-7 in the C-terminal could significantly increase CDNF secretion. Moreover, we identified the 149aa-154aa is the key amino acids in helix-7. In all, these findings suggest that helix-7 in the C-terminal is important for CDNF secretion, which maybe potential affect CDNF function in ER stress. PMID- 26271592 TI - Magnetic nanoparticle-based drug delivery for cancer therapy. AB - Nanoparticles have belonged to various fields of biomedical research for quite some time. A promising site-directed application in the field of nanomedicine is drug targeting using magnetic nanoparticles which are directed at the target tissue by means of an external magnetic field. Materials most commonly used for magnetic drug delivery contain metal or metal oxide nanoparticles, such as superparamagnetic iron oxide nanoparticles (SPIONs). SPIONs consist of an iron oxide core, often coated with organic materials such as fatty acids, polysaccharides or polymers to improve colloidal stability and to prevent separation into particles and carrier medium [1]. In general, magnetite and maghemite particles are those most commonly used in medicine and are, as a rule, well-tolerated. The magnetic properties of SPIONs allow the remote control of their accumulation by means of an external magnetic field. Conjugation of SPIONs with drugs, in combination with an external magnetic field to target the nanoparticles (so-called "magnetic drug targeting", MDT), has additionally emerged as a promising strategy of drug delivery. Magnetic nanoparticle-based drug delivery is a sophisticated overall concept and a multitude of magnetic delivery vehicles have been developed. Targeting mechanism-exploiting, tumor specific attributes are becoming more and more sophisticated. The same is true for controlled-release strategies for the diseased site. As it is nearly impossible to record every magnetic nanoparticle system developed so far, this review summarizes interesting approaches which have recently emerged in the field of targeted drug delivery for cancer therapy based on magnetic nanoparticles. PMID- 26271597 TI - Dehydrodiconiferyl alcohol suppresses monocyte adhesion to endothelial cells by attenuation of JNK signaling pathway. AB - Several clinical studies have shown that the intake of aged garlic extract improves endothelial dysfunction. Lignan compounds, (+)-(2S,3R) dehydrodiconiferyl alcohol (DDC) and (-)-(2R,3S)-dihydrodehydrodiconiferyl alcohol (DDDC), have been isolated as antioxidants in aged garlic extract. There is evidence showing the importance of oxidative stress in endothelial dysfunction. In the present study, we examined whether DDC and DDDC enhance endothelial cell function in vitro. Cell adhesion assay was performed using THP-1 monocyte and human umbilical vein endothelial cells (HUVECs) which were activated by lipopolysaccharide (LPS) or advanced glycation end products (AGEs)-BSA. Cellular ELISA method was used for the evaluation of vascular cell adhesion molecule 1 (VCAM-1) expression on HUVECs. DDC and DDDC suppressed the adhesion of THP-1 to HUVECs which was activated by LPS or AGEs-BSA. DDC and DDDC also inhibited VCAM-1 expression induced by LPS or AGEs-BSA, but DDDC was less effective than DDC. In addition, the inhibitory effect of DDC on VCAM-1 expression involved suppressing JNK/c-Jun pathway rather than NF-kappaB pathway. DDC has an inhibitory effect on VCAM-1 expression via JNK pathway in endothelial cells and therefore may serve as a novel pharmacological agent to improve endothelial dysfunction. PMID- 26271595 TI - Lithium protects against methamphetamine-induced neurotoxicity in PC12 cells via Akt/GSK3beta/mTOR pathway. AB - Methamphetamine (MA) is neurotoxic, especially in dopaminergic neurons. Long lasting exposure to MA causes psychosis and increases the risk of Parkinson's disease. Lithium (Li) is a known mood stabilizer and has neuroprotective effects. Previous studies suggest that MA exposure decreases the phosphorylation of Akt/GSK3beta pathway in vivo, whereas Li facilitates the phosphorylation of Akt/GSK3beta pathway. Moreover, GSK3beta and mTOR are implicated in the locomotor sensitization induced by psychostimulants and mTOR plays a critical role in MA induced toxicity. However, the effect of MA on Akt/GSK3beta/mTOR pathway has not been fully investigated in vitro. Here, we found that MA exposure significantly dephosphorylated Akt/GSK3beta/mTOR pathway in PC12 cells. In addition, Li remarkably attenuated the dephosphorylation effect of MA exposure on Akt/GSK3beta/mTOR pathway. Furthermore, Li showed obvious protective effects against MA toxicity and LY294002 (Akt inhibitor) suppressed the protective effects of Li. Together, MA exposure dephosphorylates Akt/GSK3beta/mTOR pathway in vitro, while lithium protects against MA-induced neurotoxicity via phosphorylation of Akt/GSK3beta/mTOR pathway. PMID- 26271596 TI - Lamp-2 deficiency prevents high-fat diet-induced obese diabetes via enhancing energy expenditure. AB - Autophagy process is essential for maintaining intracellular homeostasis and consists of autophagosome formation and subsequent fusion with lysosome for degradation. Although the role of autophagosome formation in the pathogenesis of diabetes has been recently documented, the role of the latter process remains unclear. This study analyzed high-fat diet (HFD)-fed mice lacking lysosome associated membrane protein-2 (lamp-2), which is essential for the fusion with lysosome and subsequent degradation of autophagosomes. Although lamp-2 deficient mice showed little alteration in glucose metabolism under normal diet feeding, they showed a resistance against high-fat diet (HFD)-induced obesity, hyperinsulinemic hyperglycemia and tissues lipid accumulation, accompanied with higher energy expenditure. The expression levels of thermogenic genes in brown adipose tissue were significantly increased in HFD-fed lamp-2-deficient mice. Of some serum factors related to energy expenditure, the serum level of fibroblast growth factor (FGF) 21 and its mRNA expression level in the liver were significantly higher in HFD-fed lamp-2-deficient mice in an ER stress-, but not PPARalpha-, dependent manner. In conclusion, a lamp-2-depenedent fusion and degradation process of autophagosomes is involved in the pathogenesis of obese diabetes, providing a novel insight into autophagy and diabetes. PMID- 26271599 TI - Assays for therapeutic drug monitoring of beta-lactam antibiotics: A structured review. AB - In some patient groups, including critically ill patients, the pharmacokinetics of beta-lactam antibiotics may be profoundly disturbed due to pathophysiological changes in distribution and elimination. Therapeutic drug monitoring (TDM) is a strategy that may help to optimise dosing. The aim of this review was to identify and analyse the published literature on the methods used for beta-lactam quantification in TDM programmes. Sixteen reports described methods for the simultaneous determination of three or more beta-lactam antibiotics in plasma/serum. Measurement of these antibiotics, due to low frequency of usage relative to some other tests, is generally limited to in-house chromatographic methods coupled to ultraviolet or mass spectrometric detection. Although many published methods state they are fit for TDM, they are inconvenient because of intensive sample preparation and/or long run times. Ideally, methods used for routine TDM should have a short turnaround time (fast run-time and fast sample preparation), a low limit of quantification and a sufficiently high upper limit of quantification. The published assays included a median of 6 analytes [interquartile range (IQR) 4-10], with meropenem and piperacillin being the most frequently measured beta-lactam antibiotics. The median run time was 8 min (IQR 5.9-21.3 min). There is also a growing number of methods measuring free concentrations. An assay that measures antibiotics without any sample preparation would be the next step towards real-time monitoring; no such method is currently available. PMID- 26271598 TI - Combined anti CXC receptors 1 and 2 therapy is a promising anti-inflammatory treatment for respiratory diseases by reducing neutrophil migration and activation. AB - Neutrophil infiltration and activation in the lung are important pathophysiological features in COPD, severe asthma and bronchiectasis mostly mediated by CXCL8 and CXCL1 via CXCR1 and CXCR2. No thorough study to date has been performed to compare the anti-inflammatory effect profile of dual CXCR1/2 vs. selective CXCR2 antagonists in relevant human neutrophil assays and pulmonary inflammation models. Dual CXCR1/2 (SCH527123, diaminocyclobutandione-1) and selective CXCR2 (SB265610, thiopyrimidine-1) antagonist activity and receptor residence time were determined by [(35)S]GTPgammaS binding in human (h)- and guinea pig (gp)-CXCR1 and CXCR2 overexpressing membranes. h-neutrophil chemotaxis, degranulation and ROS production were established using CXCL8 or CXCL1 to evaluate dual CXCR1/2- or selective CXCR2-dependent activities. LPS induced lung inflammation in gp was selected to assess in vivo potency. Dual CXCR1/2 antagonists blocked both CXCL8 and CXCL1-induced h-neutrophil functions and [(35)S]GTPgammaS binding. In contrary, selective CXCR2 antagonists displayed significantly reduced potency in CXCL8 -mediated h-neutrophil responses despite being active in CXCR2 assays. Upon LPS challenge in gp, administration of SCH527123 inhibited the increase of neutrophils in BALF, modestly reduced blood neutrophils and induced minor neutrophil accumulation in bone marrow. Differentiation of CXCR1/2 vs. CXCR2 antagonists could not be extended to in vivo due to differences in CXCR1 receptor homology between h and gp. Dual CXCR1/2 therapy may represent a promising anti-inflammatory treatment for respiratory diseases reducing more effectively neutrophil migration and activation in the lung than a CXCR2 selective treatment. However, the in vivo confirmation of this claim is still missing due to species differences in CXCR1. PMID- 26271601 TI - Multiple Sclerosis Mortality Rates in Canada, 1975-2009. AB - BACKGROUND: This study examined mortality due to multiple sclerosis (MS) in Canada, 1975-2009 to determine whether there has been a change in age at death relative to the general population and decrease in MS mortality rates. METHODS: Mortality rates/100,000 population for MS and all causes were calculated using data derived from Statistics Canada, age-standardized to the 2006 population. RESULTS: The average annual Canadian MS mortality rate, 1975-2009 was 1.23/100,000. Five-year rates for 1975-79, 1980-84, 1985-89, 1990-94, 1995-99, 2000-04, 2005-09 were: 1.16, 0.94, 1.01, 1.16, 1.30, 1.43, 1.33. Trend analysis showed mortality rates over the entire 35 years were stable (average annual percent change of less than one percent). The average annual 1975-2009 rates for females and males were 1.45 and 0.99. Five-year female rates were always higher than males. Regardless of gender, there was a decrease in MS mortality rates in the 0-39 age group and increases in the 60-69, 70-79, and 80+ groups over time. In contrast, there were decreases in all-cause mortality rates across each age group. The highest MS mortality rates for 1975-2009 were consistently in the 50 59 and 60-69 groups for both genders, while the highest all-cause mortality rates were in the 80+ group. CONCLUSIONS: Changes in the age distribution of MS mortality rates indicate a shift to later age at death, possibly due to improved health care. However MS patients remain disadvantaged relative to the general population and changes in age at death are not reflected in decreased mortality rates. PMID- 26271600 TI - A shrimp pacifastin light chain-like inhibitor: molecular identification and role in the control of the prophenoloxidase system. AB - Pacifastin is a recently classified family of serine proteinase inhibitors that play essential roles in various biological processes, including in the regulation of the melanization cascade. Here, a novel pacifastin-related gene, termed PmPacifastin-like, was identified from a reverse suppression subtractive hybridization (SSH) cDNA library created from hemocytes of the prophenoloxidase PmproPO1/2 co-silenced black tiger shrimp Penaeus monodon. The full-length sequences of PmPacifastin-like and its homologue LvPacifastin-like from the Pacific white shrimp Litopenaeus vannamei were determined. Sequence analysis revealed that both sequences contained thirteen conserved pacifastin light chain domains (PLDs), followed by two putative kunitz domains. Expression analysis demonstrated that the PmPacifastin-like transcript was expressed in all tested shrimp tissues and larval developmental stages, and its expression responded to Vibrio harveyi challenge. To gain insight into the functional roles of PmPacifastin-like protein, the in vivo RNA interference experiment was employed; the results showed that PmPacifastin-like depletion strongly increased PO activity. Interestingly, suppression of PmPacifastin-like also down-regulated the expression of the proPO-activating enzyme PmPPAE2 transcript; the PmPacifastin like transcript was down-regulated after the PmproPO1/2 transcripts were silenced. Taken together, these results suggest that PmPacifastin-like is important in the shrimp proPO system and may play an essential role in shrimp immune defense against bacterial infection. These results also expand the knowledge of how pacifastin-related protein participates in the negative regulation of the proPO system in shrimp. PMID- 26271603 TI - Self-powered thin-film motion vector sensor. AB - Harnessing random micromeso-scale ambient energy is not only clean and sustainable, but it also enables self-powered sensors and devices to be realized. Here we report a robust and self-powered kinematic vector sensor fabricated using highly pliable organic films that can be bent to spread over curved and uneven surfaces. The device derives its operational energy from a close-proximity triboelectrification of two surfaces: a polytetrafluoroethylene film coated with a two-column array of copper electrodes that constitutes the mover and a polyimide film with the top and bottom surfaces coated with a two-column aligned array of copper electrodes that comprises the stator. During relative reciprocations, the electrodes in the mover generate electric signals of +/-5 V to attain a peak power density of >=65 mW m(-2) at a speed of 0.3 ms(-1). From our 86,000 sliding motion tests of kinematic measurements, the sensor exhibits excellent stability, repeatability and strong signal durability. PMID- 26271604 TI - Getting to Know Viral Evolutionary Strategies: Towards the Next Generation of Quasispecies Models. AB - Viral populations are formed by complex ensembles of genomes with broad phenotypic diversity. The adaptive strategies deployed by these ensembles are multiple and often cannot be predicted a priori. Our understanding of viral dynamics is mostly based on two kinds of empirical approaches: one directed towards characterizing molecular changes underlying fitness changes and another focused on population-level responses. Simultaneously, theoretical efforts are directed towards developing a formal picture of viral evolution by means of more realistic fitness landscapes and reliable population dynamics models. New technologies, chiefly the use of next-generation sequencing and related tools, are opening avenues connecting the molecular and the population levels. In the near future, we hope to be witnesses of an integration of these still decoupled approaches, leading into more accurate and realistic quasispecies models able to capture robust generalities and endowed with a satisfactory predictive power. PMID- 26271602 TI - Duration of an intense laser pulse can determine the breakage of multiple chemical bonds. AB - Control over the breakage of a certain chemical bond in a molecule by an ultrashort laser pulse has been considered for decades. With the availability of intense non-resonant laser fields it became possible to pre-determine femtosecond to picosecond molecular bond breakage dynamics by controlled distortions of the electronic molecular system on sub-femtosecond time scales using field-sensitive processes such as strong-field ionization or excitation. So far, all successful demonstrations in this area considered only fragmentation reactions, where only one bond is broken and the molecule is split into merely two moieties. Here, using ethylene (C2H4) as an example, we experimentally investigate whether complex fragmentation reactions that involve the breakage of more than one chemical bond can be influenced by parameters of an ultrashort intense laser pulse. We show that the dynamics of removing three electrons by strong-field ionization determines the ratio of fragmentation of the molecular trication into two respectively three moieties. We observe a relative increase of two-body fragmentations with the laser pulse duration by almost an order of magnitude. Supported by quantum chemical simulations we explain our experimental results by the interplay between the dynamics of electron removal and nuclear motion. PMID- 26271605 TI - Label-Free Biosensing with High Selectivity in Complex Media using Microtoroidal Optical Resonators. AB - Although label-free biosensors comprised of optical microcavities inherently possess the capability of resolving molecular interactions at individual level, this extreme sensitivity restricts their convenience for large scale applications by inducing vulnerability towards non-specific interactions that readily occur within complex media. Therefore, the use of optical microresonators for biosensing is mostly limited within strictly defined laboratory conditions, instead of field applications as early detection of cancer markers in blood, or identification of contamination in food. Here, we propose a novel surface modification strategy suitable for but not limited to optical microresonator based biosensors, enabling highly selective biosensing with considerable sensitivity as well. Using a robust, silane-based surface coating which is simultaneously protein resistant and bioconjugable, we demonstrate that it becomes possible to perform biosensing within complex media, without compromising the sensitivity or reliability of the measurement. Functionalized microtoroids are successfully shown to resist nonspecific interactions, while simultaneously being used as sensitive biological sensors. This strategy could pave the way for important applications in terms of extending the use of state-of-the-art biosensors for solving problems similar to the aforementioned. PMID- 26271606 TI - Treatment outcomes, health-care resource utilization and costs of bortezomib and dexamethasone, with cyclophosphamide or lenalidomide, in newly diagnosed multiple myeloma. PMID- 26271608 TI - Correction: Magnetically induced structural anisotropy in binary colloidal gels and its effect on diffusion and pressure driven permeability. AB - Correction for 'Magnetically induced structural anisotropy in binary colloidal gels and its effect on diffusion and pressure driven permeability' by Christoffer Abrahamsson et al., Soft Matter, 2014, 10, 4403-4412. PMID- 26271607 TI - Stearic acid induces proinflammatory cytokine production partly through activation of lactate-HIF1alpha pathway in chondrocytes. AB - The biomechanics stress and chronic inflammation in obesity are causally linked to osteoarthritis. However, the metabolic factors mediating obesity-related osteoarthritis are still obscure. Here we scanned and identified at least two elevated metabolites (stearic acid and lactate) from the plasma of diet-induced obese mice. We found that stearic acid potentiated LDH-a-dependent production of lactate, which further stabilized HIF1alpha protein and increased VEGF and proinflammatory cytokine expression in primary mouse chondrocytes. Treatment with LDH-a and HIF1alpha inhibitors notably attenuated stearic acid-or high fat diet stimulated proinflammatory cytokine production in vitro and in vivo. Furthermore, positive correlation of plasma lactate, cartilage HIF1alpha and cytokine levels with the body mass index was observed in subjects with osteoarthritis. In conclusion, saturated free fatty acid induced proinflammatory cytokine production partly through activation of a novel lactate-HIF1alpha pathway in chondrocytes. Our findings hold promise of developing novel clinical strategies for the management of obesity-related diseases such as osteoarthritis. PMID- 26271610 TI - Characterization of the phase behaviour of a novel polymerizable lyotropic ionic liquid crystal. AB - The development of new polymerizable lyotropic liquid crystals (LLCs) utilizing charged amphiphilic molecules such as those based on long chain imidazolium compounds, is a relatively new design direction for producing robust membranes with controllable nano-structures. Here we have developed a novel polymerizable ionic liquid based LLC, 1-hexadecyl-3-methylimidazolium acrylate (C16mimAcr), where the acrylate anion acts as the polymerizable moiety. The phase behaviour of the C16mimAcr upon the addition of water was characterized using small and wide angle X-ray scatterings, differential scanning calorimetry and polarized optical microscopy. We compare the phase behaviour of this new polymerizable LLC to that of the well known LLC chloride analogue, 1-hexadecyl-3-methylimidazolium chloride (C16mimCl). We find that the C16mimAcr system has a more complex phase behaviour compared to the C16mimCl system. Additional lyotropic liquid crystalline mesophases such as hexagonal phase (H1) and discontinuous cubic phase (I1) are observed at 20 degrees C for the acrylate system at 50 and 65 wt% water respectively. The appearance of the hexagonal phase (H1) and discontinuous cubic phase (I1) for the acrylate system is likely due to the strong hydrating nature of the acrylate anion, which increases the head group area. The formation of these additional mesophases seen for the acrylate system, especially the hexagonal phase (H1), coupled with the polymerization functionality offers great potential in the design of advanced membrane materials with selective and anisotropic transport properties. PMID- 26271609 TI - Electrophysiological Investigations of Shape and Reproducibility of Oropharyngeal Swallowing: Interaction with Bolus Volume and Age. AB - Electrophysiological assessment provides valuable information on physiological and pathophysiological characteristics of human swallowing. Here, new electrophysiological measures for the evaluation of oropharyngeal swallowing were assessed: (1) the activation pattern of the submental/suprahyoid EMG activity (SHEMG); (2) the reproducibility of the oral and pharyngeal phases of swallowing, by calculating the similarity index (SI) of the SHEMG (SI-SHEMG) and of the laryngeal-pharyngeal mechanogram (SI-LPM) during repeated swallows; and (3) kinesiological measures related to the LPM. An electrophysiological-mechanical method for measuring the activation pattern of the SHEMG, the SI-SHEMG, and the SI-LPM, and maximal LPM velocity and acceleration during swallowing was applied in 65 healthy subjects divided into three age groups (18-39, 40-59, 60 years or over). All the measures were assessed during three trials of eight consecutive swallows of different liquid bolus volumes (3, 12, and 20 ml). A high overall reproducibility of oropharyngeal swallowing in healthy humans was recorded. However, while values of SI-SHEMG were similar in all the age groups, the SI-LPM was found to fall significantly in the older age group. Both the SI-SHEMG and the SI-LPM were found to fall with increasing bolus volumes. The activation pattern of the SHEMG and the LPM kinesiological measures were differently modified by bolus volume and age in the older subjects with respect to the others. We describe a new approach to the electrophysiological study of swallowing based on computed semi-automatic analyses. Our findings provide insight into some previously uninvestigated aspects of oropharyngeal swallowing physiology, considered in relation to bolus volume and age. The new electrophysiological measures here described could prove useful in the clinical setting, as it is likely that they could be differently affected in patients with different kinds of dysphagia. PMID- 26271611 TI - Comparison between Ki67 labeling index determined using image analysis software with virtual slide system and that determined visually in breast cancer. AB - BACKGROUND: In recent papers, Ki67 labeling index (LI) has been used to classify breast cancer patients into the low and high Ki67LI groups for comparison studies, which showed significant differences in many prognostic factors. It has not been clarified whether image analysis software can be used for calculating LI in breast cancer. In our study, we examined whether Ki67LI in breast cancer calculated using image analysis software correlates with that measured on the basis of visual. METHODS: Fifty patients were randomly selected among breast cancer patients who underwent surgical operation from March, 2010 to May, 2010 in our hospital without preoperative chemotherapy. In this study, for the virtual slide system (VSS: VS120-L100, Olympus, Tokyo, Japan), the high-resolution VSs of all the 50 patients were prepared as samples. The image analysis software use for calculating LI was Tissuemorph Digital Pathology (Tissuemorph DP: Visiopharm, Hoersholm, Denmark). The calculated LI was extracted from 3 to 5 views containing hot spots. The LI calculated using Tissuemorph DP was designed as LI/image/T. The digital image of 3 to 5 LI/image/T views was printed out, and on the digital photograph, we counted visually the number of Ki67-immunopositive cells in exactly the same area, and the percentage of Ki67-immunopositive cells was designed as LI/direct. Moreover, a pathologist's assistant (PA) determined the tumor area in the same specimen using VSS and calculated LI using Tissuemorph DP, which was designed as LI/image/PA. The chief pathologist (CP) similarly calculated LI which was designed as LI/image/CP. We evaluated the degree of agreement between different data sets "LI/image/T and LI/direct" and "LI/image/T, LI/image/CP, and LI/image/PA" by using interclass correlation coefficient (ICC). RESULTS: The average counts of cells were as follows: LI/direct, 3209.7 +/- 1970.4 (SD); LI/image/T, 2601.6 +/- 1697.1; LI/image/PA, 2886.5 +/- 2027.5; LI/image/CP, 18805.5 +/- 22293.4. The values of LI/direct and LI/image/T showed almost perfect agreement as showed by an ICC of 0.885 (95 % CI, 0.806-0.933; p < 0.001). The agreement among three investigators was almost perfect. The obtained ICC was 0.825 (95 % CI, 0.739-0.890; p < 0.001) among the data of LI/image/T, LI/image/CP and LI/image/PA. There were five cases that immunopositivity for Ki67 showed a more than 10 % disagreement between LI/direct and LI/image/T. CONCLUSION: The merits of calculating Ki67 LI using Tissuemorph DP are as follows. First, the staining intensity of the cells to be counted can be adjusted. Second, the portion of a tumor including "hot spots" for counting can be chosen. Third, many cancer cells can be counted more rapidly using Tissuemorph DP than by visual observation. However, it is important that pathologist should check and carry out the final decision of the data, when Ki67 LI using Tissuemorph DP is calculated. PMID- 26271612 TI - Using Heavy Metal Content and Lipid Peroxidation Indicators in the Tissues of the Mussel Crenomytilus grayanus for Pollution Assessment After Marine Environmental Remediation. AB - We examined the effects of environmental remediation on the heavy metal concentration and lipid peroxidation activity in the digestive gland and gills of the marine mussel Crenomytilus grayanus. Changes in heavy metal concentrations and lipid peroxidation biomarkers in the tissues of mussels collected at a contaminated site were compared with those obtained from a reference site. Prior to remediation the concentration of Pb, Cu, Cd, Fe and Zn and the levels of malondialdehyde, conjugated dienes and lipofuscin in mussels collected from the contaminated site were significantly increased compared with those obtained from the reference site. Three years after remediation, these parameters did not significantly exceed the reference site parameters, except Pb, whose concentration, though markedly decreased, yet was much higher than in tissues of mussels from the reference site. PMID- 26271613 TI - Accumulation and Risk of Triclosan in Surface Sediments Near the Outfalls of Municipal Wastewater Treatment Plants. AB - Triclosan is an antimicrobial agent which is widely used in many personal care products. This toxic chemical is frequently found in the aquatic environment. The municipal wastewater treatment plant (WWTP) effluent has been reported to be one of the major sources for triclosan in the aquatic system. The aim of the present study was to investigate the accumulation of triclosan in the surface sediments near the outfalls of the five major municipal WWTPs of Nanjing, China, as well as to evaluate its potential ecological risk. The concentration of triclosan in the sediment samples ranged from 48.3 to 226 ng/g dry weight, which was well correlated with the acute and genetic toxicity by bioassay. The results suggested that triclosan released from municipal WWTPs could accumulate in the surface sediments nearby and may pose undetermined risk to aquatic organisms. PMID- 26271616 TI - Important Issues Regarding Serum 25-Hydroxy Vitamin D Measurement in Inflammatory Bowel Disease Patients. PMID- 26271615 TI - Fecal Human beta-Defensin 2 in Children with Cystic Fibrosis: Is There a Diminished Intestinal Innate Immune Response? AB - BACKGROUND: Defects in bacterial host defenses in the cystic fibrosis (CF) airways have been extensively investigated, but the role of the intestinal innate immune system in CF is unknown. Human beta-defensin 2 (HBD-2) is an antimicrobial protein produced by epithelial surfaces and upregulated by inflammation. Its expression in the CF intestine is unknown. AIM: To determine whether HBD-2 was present in the feces of patients with CF, and to compare fecal HBD-2 levels between CF and healthy controls (HC). To compare fecal HBD-2 levels in inflamed and noninflamed states, as measured by fecal calprotectin, as a secondary aim. METHODS: Feces from children with CF and HC were collected for analysis. RESULTS: Thirty-three CF patients and 33 HC were recruited. All CF patients had detectable fecal HBD-2. There was no difference between fecal HBD-2 in CF and HC (median (IQR) 49.1 (19.7-77.2) versus 43.4 (26.5-71.9) ng/g; P = 0.7). Fecal calprotectin was significantly higher in the CF cohort than in HC (median (IQR) 61.3 (43.8 143.8) versus 19.5 (19.5-35.1) mg/kg; P < 0.0001). There was no difference in fecal HBD-2 levels between CF subjects with fecal calprotectin >=50 mg/kg and <50 mg/kg (50.5 (19.6-80.2) versus 43.0 (19.0-70.4); P = 0.7). There was no correlation between fecal HBD-2 and calprotectin in CF (r = 0.14; P = 0.4). CONCLUSION: Fecal HBD-2 levels were not increased in children with CF, in inflamed or noninflamed states. The lack of HBD-2 induction and upregulation under inflammatory conditions may suggest a diminished intestinal innate immune response in CF. PMID- 26271614 TI - L-Methionine repressible promoters for tuneable gene expression in Trichoderma reesei. AB - BACKGROUND: Trichoderma reesei is the main producer of lignocellulolytic enzymes that are required for plant biomass hydrolysis in the biorefinery industry. Although the molecular toolbox for T. reesei is already well developed, repressible promoters for strain engineering and functional genomics studies are still lacking. One such promoter that is widely employed for yeasts is that of the L-methionine repressible MET3 gene, encoding ATP sulphurylase. RESULTS: We show that the MET3 system can only be applied for T. reesei when the cellulase inducing carbon source lactose is used but not when wheat straw, a relevant lignocellulosic substrate for enzyme production, is employed. We therefore performed a transcriptomic screen for genes that are L-methionine repressible in a wheat straw culture. This analysis retrieved 50 differentially regulated genes of which 33 were downregulated. Among these, genes encoding transport proteins as well as iron containing DszA like monooxygenases and TauD like dioxygenases were strongly overrepresented. We show that the promoter region of one of these dioxygenases can be used for the strongly repressible expression of the Aspergillus niger sucA encoded extracellular invertase in T. reesei wheat straw cultures. This system is also portable to other carbon sources including D glucose and glycerol as demonstrated by the repressible expression of the Escherichia coli lacZ encoded beta-galactosidase in T. reesei. CONCLUSION: We describe a novel, versatile set of promoters for T. reesei that can be used to drive recombinant gene expression in wheat straw cultures at different expression strengths and in an L-methionine repressible manner. The dioxygenase promoter that we studied in detail is furthermore compatible with different carbon sources and therefore applicable for manipulating protein production as well as functional genomics with T. reesei. PMID- 26271618 TI - Chiral gamma-Lactams by Enantioselective Palladium(0)-Catalyzed Cyclopropane Functionalizations. AB - Cyclopropanes fused to pyrrolidines are important structural features found in a number of marketed drugs and development candidates. Typically, their synthesis involves the cyclopropanation of a dihydropyrrole precursor. Reported herein is a complementary approach which employs a palladium(0)-catalyzed C-H functionalization of an achiral cyclopropane to close the pyrrolidine ring in an enantioselective manner. In contrast to aryl-aryl couplings, palladium(0) catalyzed C-H functionalizations involving the formation of C(sp(3) )-C(sp(3) ) bonds of saturated heterocycles are very scarce. The presented strategy yields cyclopropane-fused gamma-lactams from chloroacetamide substrates. A bulky Taddol phosphonite ligand in combination with adamantane-1-carboxylic acid as a cocatalyst provides the gamma-lactams in excellent yields and enantioselectivities. PMID- 26271617 TI - Fucoxanthin Enhances Chain Elongation and Desaturation of Alpha-Linolenic Acid in HepG2 Cells. AB - Dietary fucoxanthin (FX), a carotenoid compound from brown algae, was found to increase docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (ARA, 20:4n-6) in the liver of mice. DHA and ARA are known to be biosynthesized from the respective precursor alpha-linolenic acid (ALA, 18:3n-3) and linoleic acid (LNA, 18:2n-6), through desaturation and chain elongation. We examined the effect of FX on the fatty acid metabolism in HepG2 cells (Hepatocellular carcinoma, human). In the first experiment, cells were co-treated with ALA (100 MUM) and FX (0-100 MUM) or vehicle for 48 h. FX increased eicosapentaenoic acid (EPA, 20:5n-3), docosapentaenoic acid (DPA, 22:5n-3), DHA at concentrations of >= 50 MUM. To clarify the change in the metabolism of polyunsaturated fatty acid (PUFA), in the second experiment, cells were co-treated with universally-[(13)C]-labeled (U [(13)C]-) ALA (100 MUM) and FX (100 MUM) for 0.5, 3, 6, 24 and 48 h. [(13)C] labeled-EPA, DPA and DHA content in HepG2 cells were all increased by FX after 48 h treatment. Furthermore, estimated delta-5 desaturase (D5D) but not delta-6 desaturase (D6D) activity index was increased at 48 h. These results suggested that FX may enhance the conversion of ALA to longer chain n-3 PUFA through increasing D5D activity in the liver. PMID- 26271619 TI - Physician report cards and rankings yield long-lasting hand hygiene compliance exceeding 90%. AB - INTRODUCTION: Hand hygiene is an effective, low-cost intervention that prevents the spread of multidrug-resistant bacteria. Despite mandatory education and reminders, compliance by physicians in our hospital remained stubbornly low. Our objective was to study whether surveillance by our unit coordinator (secretary) paired with regular feedback to chiefs of service would increase physician hand hygiene compliance in the ICU. METHOD: The ICU unit coordinator was trained to observe and measure hand hygiene compliance. Data were collected on hand hygiene compliance at room entry and exit for 9 months. Percentage compliance for each medical and surgical subspecialty was reported to chiefs of service at the end of each month. Comparative rankings by service were widely distributed throughout the physician organization and the medical center. RESULTS: The hand hygiene compliance rate among physicians increased from 65.1% to 91.6% during the study period (p < 0.0001). More importantly in the succeeding 24 months after study completion, physician hand hygiene compliance remained >90% in every month. CONCLUSIONS: Physician hand hygiene compliance increased as a consequence of the surveillance conducted by a full-time ICU team member, leading to a highly significant increase in the number of observations. In turn, this allowed for specific comparative monthly feedback to individual chiefs of service. Over the next 2 years after the study ended, these gains were sustained, suggesting an enduring culture change in physician behavior. PMID- 26271620 TI - Incidence of malignancy in adult patients with rheumatoid arthritis: a meta analysis. AB - INTRODUCTION: Patients with rheumatoid arthritis (RA) are at an increased risk of malignancies compared with the general population. This has raised concerns regarding these patients, particularly with the widespread use of immunomodulating therapies, including biologic disease-modifying antirheumatic drugs (DMARDs). We performed a systematic literature review and analysis to quantify the incidence of malignancies in patients with RA and the general population to update previously published data. METHODS: A literature search was conducted that was consistent with and similar to that in a meta-analysis published in 2008. MEDLINE, BIOSIS Previews, Embase, Derwent Drug File and SciSearch databases were searched using specified search terms. Predefined inclusion criteria identified the relevant observational studies published between 2008 and 2014 that provided estimates of relative risk of malignancy in patients with RA compared with the general population. Risk data on overall malignancy and site-specific malignancies (lymphoma, melanoma and lung, colorectal, breast, cervical and prostate cancer) were extracted. The standardized incidence ratios (SIRs; a measure of risk) relative to the general population were evaluated and compared with published rates. RESULTS: A total of nine publications met the inclusion criteria. Seven of these reported SIRs for overall malignancy; eight for lymphoma, melanoma, and lung, colorectal and breast cancer; seven for prostate cancer; and four for cervical cancer. Compared with those in the general population, the SIR estimates for patients with RA suggest a modest increased risk in overall malignancy, as previously observed. Patients with RA continued to show an increased risk of lymphoma and lung cancer compared with the general population. Overall, SIR estimates for colorectal and breast cancers continued to show a decrease in risk, whereas cervical cancer, prostate cancer and melanoma appeared to show no consistent trend in risk among patients with RA compared with the general population. CONCLUSIONS: The additional data evaluated here are consistent with previously reported data. Patients with RA are at an increased risk of lung and lymphoma malignancies compared with the general population. Quantifying differences in malignancy rates between non-biologic and biologic DMARD-treated patients with RA may further highlight which malignancies may be related to treatment rather than to the underlying disease. PMID- 26271623 TI - Decadal transition of adult mortality pattern at Ballabgarh HDSS: evidence from verbal autopsy data. AB - BACKGROUND: Mortality levels and patterns are significant indicators of population health, and are of importance to prioritize the goals of health systems and efficient resource allocation. We ascertained the decadal transition of mortality pattern in adult population aged 15 years and above during the years 2002-2011. METHODS: All adult deaths aged 15 years and above during the years 2002 to 2011 were included in the study. Cause of death was ascertained by verbal autopsy tool for adults which is a validated questionnaire developed at Ballabgarh Health and Demographic Surveillance System (HDSS). Cause and age specific mortality, and mean age at death was determined for individual years. RESULTS: A total of 4,276 deaths (>=15 years) occurred in the Ballabgarh HDSS during the years 2002 to 2011. Of these, 96.8 % deaths were investigated using verbal autopsy tool. Of total deaths investigated, 60.6 % were males. Cardiovascular diseases (19.6 %) were the leading cause of death, followed by respiratory diseases (16.5 %). In the age group of 15-59 years, the most common cause of mortality was external causes of mortality (28.9 %). Most common cause of death was senility (20.8 %) in females, whereas cardiovascular diseases were commonest cause (19.6 %) in males. Road traffic injuries contributed 6.7 % deaths in males compared to 1.5 % in females. Over the years, the proportions of mortality due to cardiovascular diseases had increased (12.6 % to 18.8 %). Mortality proportions had decreased for infectious diseases (12.1 % to 9.5 %) and respiratory diseases (24.7 % to 10.9 %). Mortality due to neoplasms remained nearly stagnant (6.6 % to 6.4 %). Mean age at death due to cardiovascular diseases and neoplasm had increased from 57 years (95 % CI: 52.2-62.9) to 62 years (95 % CI: 59.2-65.4) and 58 years (95 % CI: 53.1-63.2) to 62 years (95 % CI: 57.0-66.7), respectively, during the decade. Mean age at death had decreased for road traffic injuries and infectious diseases from 41 years (95 % CI: 31.7 50.8) to 39 years (95 % CI: 34-43.4) and 53 years (95 % CI: 48.3-58.6) to 50 years (95 % CI: 44.1-55.8), respectively over the years. CONCLUSION: Mortality surveillance using verbal autopsy tool revealed a transition in cause specific deaths from respiratory diseases to cardiovascular diseases over the decade. The apparent epidemiological transition in the community demands reorientation of healthcare priorities. PMID- 26271622 TI - Risks to the fetus from diagnostic imaging during pregnancy: review and proposal of a clinical protocol. AB - Every day, medical practitioners face the dilemma of exposing pregnant or possibly pregnant patients to radiation from diagnostic examinations. Both doctors and patients often have questions about the risks of radiation. The most vulnerable period is between the 8th and 15th weeks of gestation. Deterministic effects like pregnancy loss, congenital malformations, growth retardation and neurobehavioral abnormalities have threshold doses above 100-200 mGy. The risk is considered negligible at 50 mGy and in reality no diagnostic examination exceeds this limit. The risk of carcinogenesis is slightly higher than in the general population. Intravenous iodinated contrast is discouraged, except in highly selected patients. Considering all the possible noxious effects of radiation exposure, measures to diminish radiation are essential and affect the fetal outcome. Nonionizing procedures should be considered whenever possible and every radiology center should have its own data analysis on fetal radiation exposure. In this review, we analyze existing literature on fetal risks due to radiation exposure, producing a clinical protocol to guide safe radiation use in a clinical setting. PMID- 26271621 TI - Reduction of metallic coil artefacts in computed tomography body imaging: effects of a new single-energy metal artefact reduction algorithm. AB - OBJECTIVES: We evaluated the effect of a single-energy metal artefact reduction (SEMAR) algorithm for metallic coil artefact reduction in body imaging. METHODS: Computed tomography angiography (CTA) was performed in 30 patients with metallic coils (10 men, 20 women; mean age, 67.9 +/- 11 years). Non-SEMAR images were reconstructed with iterative reconstruction alone, and SEMAR images were reconstructed with the iterative reconstruction plus SEMAR algorithms. We compared image noise around metallic coils and the maximum diameters of artefacts from coils between the non-SEMAR and SEMAR images. Two radiologists visually evaluated the metallic coil artefacts utilizing a four-point scale: 1 = extensive; 2 = strong; 3 = mild; 4 = minimal artefacts. RESULTS: The image noise and maximum diameters of the artefacts of the SEMAR images were significantly lower than those of the non-SEMAR images (65.1 +/- 33.0 HU vs. 29.7 +/- 10.3 HU; 163.9 +/- 54.8 mm vs. 10.3 +/- 19.0 mm, respectively; P < 0.001). Better visual scores were obtained with the SEMAR technique (3.4 +/- 0.6 vs. 1.0 +/- 0.0, P < 0.001). CONCLUSIONS: The SEMAR algorithm significantly reduced artefacts caused by metallic coils compared with the non-SEMAR algorithm. This technique can potentially increase CT performance for the evaluation of post-coil embolization complications. KEY POINTS: * The new algorithm involves a raw data- and image based reconstruction technique. * The new algorithm mitigates artefacts from metallic coils on body CT images. * The new algorithm significantly reduced artefacts caused by metallic coils. * The metal artefact reduction algorithm improves CT image quality after coil embolization. PMID- 26271624 TI - C-reactive protein level at 2 weeks following initiation of infliximab induction therapy predicts outcomes in patients with ulcerative colitis: a 3 year follow-up study. AB - BACKGROUND: Poor response to anti-tumour necrosis factor biologicals like infliximab (IFX) is observed in patients with ulcerative colitis (UC), which may lead to prolonged morbidity and waste of medical resources. We aimed to look for potential biomarkers of response to IFX in patients with UC who were to undergo IFX induction therapy. METHODS: Seventy-two IFX naive UC patients with partial Mayo (pMayo) score of 4-9 received IFX infusion at weeks 0, 2 and 6 as induction therapy. The pMayo score, trough IFX and C-reactive protein (CRP) concentrations were measured. At week 14, patients who achieved a pMayo score of <= 2 with no individual subscore exceeding 1 were judged as responders, while patients who responded, but did not achieve a pMayo score of <= 2 were judged as partial responders. Likewise, patients who showed unchanged pMayo score or worsened were judged as non-responders. Patients were followed for up to 3.3 years. RESULTS: Response, partial response and no response rates were 40.3, 33.3, and 26.4%, respectively. CRP level at week 2 in responders was significantly lower vs partial-responders (P = 0.0135) or non-responders (P = 0.0084) in spite of similar trough IFX level. Further, the median CRP (week 2/week 0) ratio was significantly lower in patients who responded vs partial-responders or non responders, 0.06, 0.39 and 1.00, respectively. When the cut-off value was set at 0.19 for the CRP (week 2/week 0) ratio, this ratio could predict partial responders with 79.1% sensitivity and 75.9% specificity. Patients with the CRP (week 2/week 0) ratio greater than 0.19 were likely to be partial-responder, with odds ratio 10.371 (P < 0.0001; 95% confidence interval 3.596-33.440). CONCLUSIONS: In this study, CRP level at week 2 following initiation of IFX induction therapy appeared to be a clinically relevant biomarker of response to IFX in UC patients. PMID- 26271625 TI - Can a native rodent species limit the invasive potential of a non-native rodent species in tropical agroforest habitats? AB - BACKGROUND: Little is known about native and non-native rodent species interactions in complex tropical agroecosystems. We hypothesised that the native non-pest rodent Rattus everetti may be competitively dominant over the invasive pest rodent Rattus tanezumi within agroforests. We tested this experimentally by using pulse removal for three consecutive months to reduce populations of R. everetti in agroforest habitat, and assessed over 6 months the response of R. tanezumi and other rodent species. RESULTS: Following removal, R. everetti individuals rapidly immigrated into removal sites. At the end of the study period, R. tanezumi were larger and there was a significant shift in their microhabitat use with respect to the use of ground vegetation cover following the perturbation of R. everetti. Irrespective of treatment, R. tanezumi selected microhabitat with less tree canopy cover, indicative of severely disturbed habitat, whereas R. everetti selected microhabitat with a dense canopy. CONCLUSION: Our results suggest that sustained habitat disturbance in agroforests favours R. tanezumi, while the regeneration of agroforests towards a more natural state would favour native species and may reduce pest pressure in adjacent crops. In addition, the rapid recolonisation of R. everetti suggests this species would be able to recover from non-target impacts of short-term rodent pest control. (c) 2015 Society of Chemical Industry. PMID- 26271626 TI - Immediate behavioural responses to earthquakes in Christchurch, New Zealand, and Hitachi, Japan. AB - This study examines people's immediate responses to earthquakes in Christchurch, New Zealand, and Hitachi, Japan. Data collected from 257 respondents in Christchurch and 332 respondents in Hitachi revealed notable similarities between the two cities in people's emotional reactions, risk perceptions, and immediate protective actions during the events. Respondents' physical, household, and social contexts were quite similar, but Hitachi residents reported somewhat higher levels of emotional reaction and risk perception than did Christchurch residents. Contrary to the recommendations of emergency officials, the most frequent response of residents in both cities was to freeze. Christchurch residents were more likely than Hitachi residents to drop to the ground and take cover, whereas Hitachi residents were more likely than Christchurch residents to evacuate immediately the building in which they were situated. There were relatively small correlations between immediate behavioural responses and demographic characteristics, earthquake experience, and physical, social, or household context. PMID- 26271627 TI - Direct Analysis of Leucine and Its Metabolites beta-Hydroxy-beta-methylbutyric Acid, alpha-Ketoisocaproic Acid, and alpha-Hydroxyisocaproic Acid in Human Breast Milk by Liquid Chromatography-Mass Spectrometry. AB - A direct, quantitative, and confirmatory method based on stable isotope dilution liquid chromatography-mass spectrometry was developed and validated for the analysis of leucine and metabolites beta-hydroxy-beta-methylbutyric acid (HMB), alpha-ketoisocaproic acid (KIC), and alpha-hydroxyisocaproic acid (HICA) in human breast milk. Chromatographic resolution was achieved between isobaric leucine and isoleucine. Accuracy and intermediate precision were 89-117% and <10% relative standard deviation (RSD) across three validation runs. Limits of quantitation for HMB, KIC, HICA, and leucine in human breast milk were 20 MUg/L, 20 MUg/L, 10 MUg/L, and 1 mg/L. Measured concentrations of HMB, KIC, HICA, and free leucine in human breast milk from six donors at various stages of lactation were 42-164 MUg/L, < 20-1057 MUg/L, < 10 MUg/L, and 2.1-88.5 mg/L. HMB and KIC were confirmed in human breast milk by orthogonal hydrophilic interaction chromatography (HILIC). This work provides a tool for further study of human breast milk composition and its effect on protein turnover in developing infants. PMID- 26271628 TI - Sheila Kitzinger (1929-2015). PMID- 26271629 TI - Midwifery Facilitation: Exploring the Functionality of Labor Discomfort. PMID- 26271633 TI - Recombinant oxalate decarboxylase: enhancement of a hybrid catalytic cascade for the complete electro-oxidation of glycerol. AB - The complete electro-oxidation of glycerol to CO2 is performed through an oxidation cascade using a hybrid catalytic system combining a recombinant enzyme, oxalate decarboxylase from Bacillus subtilis, and an organic oxidation catalyst, 4-amino-TEMPO. This system is capable of electrochemically oxidizing glycerol at a carbon electrode collecting all 14 electrons per molecule. PMID- 26271636 TI - Editorial: Distraction of attention by sound. PMID- 26271634 TI - Unexpected features of breast cancer subtype. AB - BACKGROUND: Gene expression profiling of breast cancers identifies distinct molecular subtypes that affect prognosis. The aim of this study was to determine whether features of tumors especially the risks of lymph node (LN) metastases differ among molecular subtypes. METHODS: Subtypes were classified by immunohistochemical surrogates as luminal A, luminalHer2-, luminalHer2+, TNBC, and HER-2+. Data were obtained from an established, registered database of patients with invasive breast cancer treated at our hospital between July 2012 and October 2014. A total of 929 tumors were classifiable into molecular subtypes. RESULTS: The distribution of subtypes was luminal A (24.2%), luminalHer2- (27.8%), luminalHer2+ (9.1%), TNBC (21.3%), and HER-2+ (17.5%). Marked differences in age, tumor size, extent of lymph node involvement, and grade were observed among subtypes. On univariate analysis, the LN positivity varied across subtypes with 33.6% in luminal A, 40.3% in luminalHer2-, 37.3% in luminalHer2+, 37.6% in TNBC, and 47.4 % in HER-2+ (p=0.201). There was no significant difference in LN positivity among subtypes. On multivariable analysis, grade and tumor size were independent predictors of LN positivity. CONCLUSIONS: Predictors of LN metastases include higher grade and larger tumor size. Even though breast cancer subtype is not a statistically significant predictor of LN positivity, this information may still be useful in selecting the appropriate therapy in clinical practice. PMID- 26271632 TI - Red blood cell storage in additive solution-7 preserves energy and redox metabolism: a metabolomics approach. AB - BACKGROUND: Storage and transfusion of red blood cells (RBCs) has a huge medical and economic impact. Routine storage practices can be ameliorated through the implementation of novel additive solutions (ASs) that tackle the accumulation of biochemical and morphologic lesion during routine cold liquid storage in the blood bank, such as the recently introduced alkaline solution AS-7. Here we hypothesize that AS-7 might exert its beneficial effects through metabolic modulation during routine storage. STUDY DESIGN AND METHODS: Apheresis RBCs were resuspended either in control AS-3 or experimental AS-7, before ultrahigh performance liquid chromatography-mass spectrometry metabolomics analysis. RESULTS: Unambiguous assignment and relative quantitation was achieved for 229 metabolites. AS-3 and AS-7 results in many similar metabolic trends over storage, with AS-7 RBCs being more metabolically active in the first storage week. AS-7 units had faster fueling of the pentose phosphate pathway, higher total glutathione pools, and increased flux through glycolysis as indicated by higher levels of pathway intermediates. Metabolite differences are especially observed at 7 days of storage, but were still maintained throughout 42 days. CONCLUSION: AS-7 formulation (chloride free and bicarbonate loading) appears to improve energy and redox metabolism in stored RBCs in the early storage period, and the differences, though diminished, are still appreciable by Day 42. Energy metabolism and free fatty acids should be investigated as potentially important determinants for preservation of RBC structure and function. Future studies will be aimed at identifying metabolites that correlate with in vitro and in vivo circulation times. PMID- 26271637 TI - Auditory distraction and perceptual organization: Streams of unconscious processing. AB - Perceptual organization is key to understanding auditory distraction. In order to achieve a fundamental understanding of distraction it is necessary to understand how auditory stimuli are perceived; specifically, how they are organized into entities that do not map directly onto simple single stimuli as defined by the experimenter. It is important not to mistake some arbitrary unit of analysis, such as the word, as the correct unit for understanding auditory processing; rather, the unit of the auditory object and its relative position to other auditory objects is the key to understanding distraction (as well as the whole of auditory cognition more generally). Here I provide two illustrative examples of auditory perceptual organization showing the superlative power of organizational principles: streaming by similarity and stimulus capture. I go on to show how these have been used to refine our understanding of distraction, and of the effects of distraction from sequences of sound, from single sounds, or single changes within a sequence. A common feature of work described here is that it compares the effects of different forms of organization: The nominal stimuli themselves are largely unchanged but the way they relate to each other can change distraction appreciably. That is, it is not the mere presence of sound that causes distraction but its organization and the way that relates to the currently prevailing activity. PMID- 26271635 TI - Diet specialization selects for an unusual and simplified gut microbiota in two- and three-toed sloths. AB - Symbiotic microbial communities are critical to the function and survival of animals. This relationship is obligatory for herbivores that engage gut microorganisms for the conversion of dietary plant materials into nutrients such as short-chain organic acids (SCOAs). The constraint on body size imposed by their arboreal lifestyle is thought to make this symbiosis especially important for sloths. Here, we use next-generation sequencing to identify the bacteria present in the fore and distal guts of wild two- and three-toed sloths, and correlate these communities with both diet and SCOAs. We show that, unlike other mammalian herbivores, sloth gut communities are dominated by the bacterial phyla Proteobacteria and Firmicutes. Specifically, three-toed sloths possess a highly conserved, low-diversity foregut community with a highly abundant Neisseria species associated with foregut lactate. In contrast, two-toed sloths have a more variable and diverse foregut microbiota correlated with a variety of SCOAs. These differences support the hypothesis that feeding behaviour selects for specific gut bacterial communities, as three-toed sloths subsist primarily on Cecropia tree leaves while two-toed sloths have a more generalist diet. The less diverse diet and gut microbiota of three-toed sloths may render them more susceptible to habitat loss and other diet-altering conditions. PMID- 26271638 TI - Auditory distraction: A duplex-mechanism account. AB - A body of laboratory work is reviewed suggesting that auditory distraction comes in two functionally distinct forms. Interference-by-process is produced when the involuntary processing of the sound competes with a similar process applied deliberately to perform a focal task. In contrast, attentional capture is produced when the sound causes a disengagement of attention away from the prevailing task, regardless of the task processes involved. Particular attention is devoted to reviewing a range of converging evidence from both experimental and individual- and group-differences-based research, indicating that auditory attentional capture is controllable via greater top-down task engagement whereas interference-by-process is not. PMID- 26271640 TI - On the development of auditory distraction: A review. AB - The present review focuses on the development of involuntary attention mechanisms in the context of the occurrence of unexpected events during childhood. We introduce a prevailing three-stage model of auditory involuntary attention describing the processes leading to, accompanying, and following the distraction of attention by prediction violations: (a) the automatic detection of prediction violations (associated with the event-related potential [ERP] component mismatch negativity [MMN]), (b) the involuntary orienting of attention processes towards the prediction violating sound (associated with the ERP component P3a), and (c) the reorienting back to task-relevant information (associated with the ERP components reorienting negativity [RON] or late discriminative negativity [LDN]). Within this framework we give an overview of studies investigating MMN, P3a, RON/LDN, and behavioral distraction effects in children. We discuss the development of the underlying involuntary attention mechanisms and highlight the relevance of and future perspectives for this important field of research. PMID- 26271639 TI - Predictability and distraction: Does the neural model represent postcategorical features? AB - Two experiments examined the role of predictability within the elements of a task irrelevant auditory sequence on the disruption produced to visual-verbal serial recall. Experiment 1 showed that participants did not benefit from having a long term representation of the irrelevant sequence: A highly predictable, canonical sequence ("1 2 3 4 5 6 7 8 9") produced as much disruption as a repeated random sequence (which was the same on each trial) and an unpredictable, random sequence (which differed on each trial), as compared with quiet. In line with this finding, there was also no difference between a predictable canonical and an unpredictable random sequence in Experiment 2. However, a deviant within the predictable, canonical sequence ("1 2 3 4 5 5 7 8 9") produced greater disruption than a deviant within an unpredictable, random sequence ("4 8 2 9 5 5 7 3 1"). This effect was confined to early trials within the block. The results showed that long-term knowledge about the order of the individual elements in the sequence did not help attenuate the effect of auditory distraction on serial recall. Nevertheless, attentional capture was amplified when a deviant violated a well-known, canonical sequence, providing evidence that the neural model represents postcategorical sequential information. PMID- 26271641 TI - Massive haemolysis and erythrophagocytosis in Gram-negative sepsis. PMID- 26271643 TI - Leukemia inhibitory factor promotes tumor growth and metastasis in human osteosarcoma via activating STAT3. AB - The leukemia inhibitory factor (LIF) has been demonstrated to be an oncogene and participated in multiple procedures during the initiation and progression of many human malignancies. However, the role of LIF in osteosarcoma is still largely unknown. Here, we performed a series of in vitro and in vivo experiments to investigate the expression and biological functions of LIF in osteosarcoma. Compared to that in the non-cancerous tissues, LIF was significantly overexpressed in a panel of 68 osteosarcoma samples (p < 0.0001). Moreover, the overexpression of LIF was significantly correlated with advanced tumor stage, larger tumor size, and shorter overall survival. In addition, knockdown of LIF notably suppressed the proliferation and invasion of osteosarcoma via blocking the STAT3 signal pathway; in contrast, treatment with the recombinant LIF protein significantly promoted the growth and invasion of osteosarcoma through enhancing the phosphorylation of STAT3, which can be partially neutralized by the STAT3 inhibitor, HO-3867. In conclusion, we demonstrated that LIF was frequently overexpressed in osteosarcoma, which could promote the growth and invasion through activating the STAT3 pathway. Our findings proposed that LIF might be a potent therapeutic target for osteosarcoma. PMID- 26271642 TI - Eosinophilic oesophagitis: relationship of quality of life with clinical, endoscopic and histological activity. AB - BACKGROUND: Knowledge about determinants of quality of life (QoL) in eosinophilic oesophagitis (EoO) patients helps to identify patients at risk of experiencing poor QoL and to tailor therapeutic interventions accordingly. AIM: To evaluate the impact of symptom severity, endoscopic and histological activity on EoE specific QoL in adult EoE patients. METHODS: Ninety-eight adult EoE patients were prospectively included (64% male, median age 39 years). Patients completed two validated instruments to assess EoE-specific QoL (EoO-QoL-A) and symptom severity (adult EoE activity index patient-reported outcome) and then underwent esophagogastroduodenoscopy with biopsy sampling. Physicians reported standardised information on EoE-associated endoscopic and histological alterations. The Spearman's rank correlation coefficient was calculated to determine the relationship between QoL and symptom severity. Linear regression and analysis of variance was used to quantify the extent to which variations in severity of EoE symptoms, endoscopic and histological findings explain variations in QoL. RESULTS: Quality of life strongly correlated with symptom severity (r = 0.610, P < 0.001). While the variation in severity of symptoms, endoscopic and histological findings alone explained 38%, 35% and 22% of the variability in EoE related QoL, respectively, these together explained 60% of variation. Symptom severity explained 18-35% of the variation in each of the five QoL subscale scores. CONCLUSIONS: Eosinophilic oesophagitis symptom severity and biological disease activity determine QoL in adult patients with eosinophilic oesophagitis. Therefore, reduction in both eosinophilic oesophagitis symptoms as well as biological disease activity is essential for improvement of QoL in adult patients. Clinicaltrials.gov number, NCT00939263. PMID- 26271644 TI - A suggestion for pathological grossing and reporting based on prognostic indicators of malignancies from a pooled analysis of renal epithelioid angiomyolipoma. AB - PURPOSE: Epithelioid angiomyolipoma (EAML) is a rare entity of the kidney. The guideline for grossing and reporting of renal EAML has not been established for Chinese patients. We planned this study to provide some preliminary indicators for draft guidelines of pathological diagnosis among Chinese people. METHODS: The histopathological characteristics of 11 EAML cases from Cancer Hospital, Chinese Academy of Medical Sciences, were reviewed, and a pooled analysis based on our cases and cases from published articles was performed on the histopathological characteristics and prognosis of 56 Chinese patients with EAML. All the cases met the criteria of the 2004 World Health Organization classification of renal tumors. RESULTS: The ratio of female to male was 1.2:1 with the mean age of 43.4 in the 11 cases. All the 11 cases were sampled following the guideline of renal cell carcinoma. The mean tumor size was 6.5 cm. Four (36.4 %) cases showed necrosis. Six (54.5 %) cases showed invasive borders. Only one case showed metastases. In pooled analysis of the total 56 cases with EAML, 10 cases (17.9 %) showed adverse prognosis. Tumor size, necrosis and invasive edge showed significant difference between favorite and adverse prognostic groups (P < 0.05). CONCLUSION: The majority of EAML is benign, and true malignant EAML is rare. The sample of EAML should follow the sample guidelines of renal cell carcinoma with some modifications, emphasizing the presence of necrosis and invading edge. The information of tumor size, necrosis and invasive edge should be included in the diagnostic report of each EAML case. PMID- 26271646 TI - Building momentum toward underactive bladder research and education. PMID- 26271645 TI - Evaluation of fine particles in surgical smoke from an urologist's operating room by time and by distance. AB - INTRODUCTION: Electrocautery, harmonic scalpel tissue dissection and other surgical techniques can generate surgical smoke with high proportion of 'fine particles' (PM(2.5)) <2.5 MUm, which is known to have adverse effects on human health. The high-risk zone for PM(2.5) during surgeries by time and by distance has not been well evaluated. METHODS: The study included open superficial, open abdominal, open pelvic, laparoscopic and transurethral urology surgeries, five of each. A particle counter was placed at three different distances from the incision site, and the real-time PM(2.5) concentration was displayed after each cut. Air Quality Index (AQI) revised by the US Environmental Protection Agency and the calculated inhalation dose were used to evaluate the severity of PM(2.5). RESULTS: In superficial, abdominal and pelvic surgeries, the peak PM(2.5) concentration may reach 245.7, 149.4 and 165.1 MUg/m(3) 3-6 s after a single cut 40 cm from the incision site. By the time, AQI usually turns to 'unhealthy' or 'very unhealthy.' In laparoscopic surgeries, 40 cm from the trocar, the air quality reached 'hazardous' in 3 s after opening of the trocar valve with a peak concentration of 517.5 MUg/m(3). In transurethral surgeries, the AQI 40 cm away from the resectoscope is generally at moderate level. In each surgery, the chief surgeon may inhale most of the PM(2.5), while the assistant will inhale less than half the dose, and the scrub nurse may inhale nearly none. The use of wall suction may induce a 48-65 % decrease in fine particle inhalation. CONCLUSIONS: During surgeries, the concentration of PM(2.5) could reach a very unhealthy status, especially for the chief surgeon who is the nearest to the incision site. Surgical smoke evacuation in the first few seconds of a cut is essential; however, using smoke evacuators such as a wall suction alone may not be enough. PMID- 26271649 TI - Language evolution as cultural evolution: how language is shaped by the brain. AB - This paper reviews arguments against the evolutionary plausibility of a traditional genetically specified universal grammar. We argue that no such universal grammar could have evolved, either by a process of natural selection or by other evolutionary mechanisms. Instead, we propose that the close fit between languages and language learners, which make language acquisition possible, arises not because humans possess a specialized biological adaptation for language, but because language has been shaped to fit the brain, a process of cultural evolution. On this account, many aspects of the structure of human languages may be explained as cultural adaptations to the human brain. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271647 TI - How well does pre-service education prepare midwives for practice: competence assessment of midwifery students at the point of graduation in Ethiopia. AB - BACKGROUND: Midwifery support and care led by midwives is the most appropriate strategy to improve maternal and newborn health. The Government of Ethiopia has recently improved the availability of midwives by scaling up pre-service education. However, the extent to which graduating students acquire core competencies for safe and effective practice is not known. The purpose of this study was to evaluate the quality of midwifery education by assessing the competence of graduating midwifery students. METHODS: We conducted a cross sectional study to assess the competence of students who completed basic midwifery education in Ethiopia in 2013. We interviewed students to obtain their perceptions of the sufficiency and quality of teachers and educational resources and processes. We assessed achievement of essential midwifery competencies through direct observation, using a 10-station Objective Structured Clinical Examination (OSCE). We calculated average percentage scores of performance for each station and an average summary score for all stations. Chi-square test, independent sample t test, and linear regression analysis were used to assess the statistical significance of differences and associations. RESULTS: We assessed 484 graduating students from 25 public training institutions. Majority of students rated the learning environment unfavorably on 8 out of 10 questions. Only 32 % of students managed 20 or more births during training, and just 6 % managed 40 or more births. Students' overall average competence score was 51.8 %; scores ranged from 32.2 % for manual vacuum aspiration to 69.4 % for active management of the third stage of labor. Male gender, reporting sufficient clinical experience, and managing greater numbers of births during training were significant predictors of higher competence scores. CONCLUSIONS: The quality of pre-service midwifery education needs to be improved, including strengthening of the learning environment and quality assurance systems. In-service training and mentoring to fill competence gaps of new graduates is also essential. PMID- 26271648 TI - Elevated transmission of upper respiratory illness among new recruits in military barracks in Thailand. AB - BACKGROUND: New recruits within military barracks present conditions favorable for the spread of respiratory pathogens. However, respiratory pathogen transmission in such confined settings in the tropics has not been well studied. METHODS: Recruits in four successive Royal Thai Army basic training classes living in military barracks were monitored for the symptoms of influenza-like illness (ILI) or upper respiratory illness (URI). Classes 1 and 2 were also monitored after basic training. Nasal/throat swabs from acute illnesses were collected and tested by influenza RT-PCR (all four classes). In addition, class 1 had multiplex PCR performed along with the analysis of bed locations within the barracks. RESULTS: Influenza-like illness/upper respiratory illness rates ranged from 4.7 to 6.9 per 100 recruit-weeks in the four classes and generally decreased during the course of basic training (P < 0.05 in three of four classes). Rates during basic training were 1.7 (95% CI: 1.29, 2.29) and 2.5 (95% CI: 1.5, 4.1) times higher than after basic training (classes 1 and 2, respectively). In class 1, coronavirus, parainfluenza virus, and rhinovirus were the most commonly identified respiratory pathogens; only one influenza PCR-positive infection was detected in all four classes. Bed locations of URI/ILI cases in class 1 tended to be in closer proximity to each other. CONCLUSION: Basic training recruits in military barracks in the tropics had high rates of acute respiratory illnesses with illness patterns consistent with external seeding followed by substantial internal transmission. Our findings may contribute to control measures in similar confined settings both within and outside the military. PMID- 26271651 TI - Bayesian data analysis. AB - Bayesian methods have garnered huge interest in cognitive science as an approach to models of cognition and perception. On the other hand, Bayesian methods for data analysis have not yet made much headway in cognitive science against the institutionalized inertia of 20th century null hypothesis significance testing (NHST). Ironically, specific Bayesian models of cognition and perception may not long endure the ravages of empirical verification, but generic Bayesian methods for data analysis will eventually dominate. It is time that Bayesian data analysis became the norm for empirical methods in cognitive science. This article reviews a fatal flaw of NHST and introduces the reader to some benefits of Bayesian data analysis. The article presents illustrative examples of multiple comparisons in Bayesian analysis of variance and Bayesian approaches to statistical power. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271650 TI - Philosophy of mind. AB - Philosophy of mind concerns questions about mental phenomena that empirical research alone can't settle, such as the nature of mental states and which sorts of things can have them-only living things, or also machines? Settling them requires reflection on such phenomena as consciousness, rationality, and intentionality; the 'explanatory gaps' that seem to exist between these; and underlying physical phenomena and the different strategies-dualist, eliminativist, physicalist, and functionalist-that have been proposed for dealing with them. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271652 TI - Language acquisition and language change. AB - Children acquire a mature language system and sometimes this system differs from that of their parents. This is a significant part of language change and understanding acquisition is key to understanding this kind of change in people's internal grammars. I outline one approach to language acquisition, based on children finding cues expressed in the input they are exposed to. This enables us to understand historical change in grammars: change in external language sometimes triggers a new internal grammar as cues come to be expressed differently. Work on language variation, acquisition, and change converges, and these three areas are mutually dependent; empirical work in one area may enrich understanding more generally, opening the way to new kinds of empirical work. Seen this way, language is a complex system and language change can be treated productively in the context of complexity science. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271653 TI - Imitation: what animal imitation tells us about animal cognition. AB - Imitation of actions is widespread in the animal kingdom, but the mental capacities thereby implied vary greatly according to the adaptive function of copying. Behavioral synchrony in social species has many possible benefits, including minimizing predation risk and using food resources optimally, but can be understood by the simple cognitive mechanism of response facilitation by priming. Imitation can send a social message, either one of short-term meshing or group identity. Where the imitative match is opaque, as in neonatal imitation, the correspondence problem may imply an innate system of behavior matching; but in other cases, no more than priming may be involved, although there are persistent suggestions that great ape imitation implies empathic abilities. Imitation in the service of learning new skills by following another's example can be divided into contextual imitation (when to employ a familiar action, and to what problem) and production imitation (learning of new skills by imitation). Cognitively, the former requires little more than response facilitation, whereas production imitation needs at least the ability to extract the statistical regularities of repeated action and to incorporate the result into hierarchical program construction. Among our close relatives, only the great apes show much evidence of production imitation of actions, along with the ability to selectively imitate the most rational components of what they observe. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271654 TI - Computational perspectives on cognitive development. AB - This article reviews the efforts to develop process models of infants' and children's cognition. Computational process models provide a tool for elucidating the causal mechanisms involved in learning and development. The history of computational modeling in developmental psychology broadly follows the same trends that have run throughout cognitive science-including rule-based models, neural network (connectionist) models, ACT-R models, ART models, decision tree models, reinforcement learning models, and hybrid models among others. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271655 TI - Understanding genetic, neurophysiological, and experiential influences on the development of executive functioning: the need for developmental models. AB - Flexibility is a cornerstone of adaptive behavior and is made possible by a family of processes referred to collectively as executive functions. Executive functions vary in efficacy from individual to individual and also across developmental time. Infants and young children, for example, have difficulty flexibly adapting their behavior, and often repeat actions that are no longer appropriate. And although older children do not typically make such striking errors, they have more difficulty exercising control than adolescents and adults. Such developmental variability parallels (at least in some respects) inter individual variability in executive functions. Individuals who suffer damage or dysfunction in regions of the prefrontal cortex, for example, often experience difficulty in flexibly adapting their behavior to changes in context. As well, genetic differences between individuals are strongly associated with differences in executive control. Parallels between developmental and inter-individual variability suggest hypotheses about possible mechanisms underlying the development of executive functions but carry risks when interpreted improperly. Overcoming these pitfalls will require mechanistic characterizations of executive functioning that are more deeply rooted in developmental principles. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271656 TI - Judgment and decision making. AB - The study of judgment and decision making entails three interrelated forms of research: (1) normative analysis, identifying the best courses of action, given decision makers' values; (2) descriptive studies, examining actual behavior in terms comparable to the normative analyses; and (3) prescriptive interventions, helping individuals to make better choices, bridging the gap between the normative ideal and the descriptive reality. The research is grounded in analytical foundations shared by economics, psychology, philosophy, and management science. Those foundations provide a framework for accommodating affective and social factors that shape and complement the cognitive processes of decision making. The decision sciences have grown through applications requiring collaboration with subject matter experts, familiar with the substance of the choices and the opportunities for interventions. Over the past half century, the field has shifted its emphasis from predicting choices, which can be successful without theoretical insight, to understanding the processes shaping them. Those processes are often revealed through biases that suggest non-normative processes. The practical importance of these biases depends on the sensitivity of specific decisions and the support that individuals have in making them. As a result, the field offers no simple summary of individuals' competence as decision makers, but a suite of theories and methods suited to capturing these sensitivities. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271658 TI - The mental representation of bilingualism. AB - This article addresses the question of how different languages are represented in our memory and how bilingual speakers access these languages in language production. The first section discusses diverse approaches to language storage. It introduces a model that considers connections between different levels of language representation, i.e., conceptual and lexical features, morpho-syntactic information, and phonological patterns. The second section is concerned with access to different languages: the focus here is on language production and models of interactive activation. The next section focuses on control mechanisms that are capable of inhibiting one language while the other is spoken. These theoretical assumptions are illustrated by authentic speech production data that provide insights into the cognitive workings of bilingual speakers. Finally, differences in mental representation due to age of acquisition or language proficiency are discussed and explained by dissimilarities in memory types and neural processes of knowledge activation. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271657 TI - Decision making under risk and uncertainty. AB - Decision making is studied from a number of different theoretical approaches. Normative theories focus on how to make the best decisions by deriving algebraic representations of preference from idealized behavioral axioms. Descriptive theories adopt this algebraic representation, but incorporate known limitations of human behavior. Computational approaches start from a different set of assumptions altogether, focusing instead on the underlying cognitive and emotional processes that result in the selection of one option over the other. This review comprehensively but concisely describes and contrasts three approaches in terms of their theoretical assumptions and their ability to account for behavioral and neurophysiological evidence from experimental research. Although each approach contributes substantially to our understanding of human decision making, we argue that the computational approach is more fruitful and parsimonious for describing and predicting choices in both laboratory and applied settings and for understanding the neurophysiological substrates of decision making. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271659 TI - Mathematical psychology. AB - Mathematical psychology is a sub-field of psychology that started in the 1950s and has continued to grow as an important contributor to formal psychological theory, especially in the cognitive areas of psychology such as learning, memory, classification, choice response time, decision making, attention, and problem solving. In addition, there are several scientific sub-areas that were originated by mathematical psychologists such as the foundations of measurement, stochastic memory models, and psychologically motivated reformulations of expected utility theory. Mathematical psychology does not include all uses of mathematics and statistics in psychology, and indeed there is a long history of such uses especially in the areas of perception and psychometrics. What is most unique about mathematical psychology is its approach to theory construction. While accepting the behaviorist dictum that the data in psychology must be observable and replicable, mathematical models are specified in terms of unobservable formal constructs that can predict detailed aspects of data across multiple experimental and natural settings. By now almost all the substantive areas of cognitive and experimental psychology have formal mathematical models and theories, and many of these are due to researchers that identify with mathematical psychology. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271660 TI - Long-term potentiation (LTP) of human sensory-evoked potentials. AB - Long-term potentiation (LTP) is the principal candidate synaptic mechanism underlying learning and memory, and has been studied extensively at the cellular and molecular level in laboratory animals. Inquiry into the functional significance of LTP has been hindered by the absence of a human model as, until recently, LTP has only been directly demonstrated in humans in isolated cortical tissue obtained from patients undergoing surgery, where it displays properties identical to those seen in non-human preparations. In this brief review, we describe the results of paradigms recently developed in our laboratory for inducing LTP-like changes in visual-, and auditory-evoked potentials. We describe how rapid, repetitive presentation of sensory stimuli leads to a persistent enhancement of components of sensory-evoked potential in normal humans. Experiments to date, investigating the locus, stimulus specificity, and NMDA receptor dependence of these LTP-like changes suggest that they have the essential characteristics of LTP seen in experimental animals. The ability to elicit LTP from non-surgical patients will provide a human model system allowing the detailed examination of synaptic plasticity in normal subjects and may have future clinical applications in the assessment of cognitive disorders. Copyright (c) 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26271661 TI - Personalizing initial calcineurin inhibitor dosing by adjusting to donor CYP3A status in liver transplant patients. AB - AIMS: Inter-individual variability in dose requirements of calcineurin inhibitors (CNI) has been linked to genetic polymorphisms of CYP3A enzymes. CYP3A5*3, CYP3A4*1B and CYP3A4*22 alleles of liver grafts may explain about one third of the inter-individual differences in pharmacokinetics of ciclosporin and tacrolimus in recipients. However, non-genetic factors, influencing CYP3A expression, can contribute to the variability of CYP3A function due to phenoconversion. The present study evaluated the association between CYP3A4 expression combined with CYP3A5 genotype of donor livers and recipients' CNI therapy after transplantation. METHODS: The contribution of donors' CYP3A5 genotype and CYP3A4 expression to the blood concentrations and dose requirements of CNIs was evaluated in 131 liver transplant recipients. RESULTS: The recipients with grafts from normal CYP3A4 expresser donors carrying CYP3A5*3/*3 required CNI maintenance doses more or less similar to the bodyweight-controlled starting doses (9.1 mg kg(-1) of ciclosporin and 0.1 mg kg(-1) of tacrolimus). The patients transplanted with grafts from low CYP3A4 expressers required substantial reduction (by about 50%, 4.2 mg kg(-1) of ciclosporin, 0.047 mg kg(-1) of tacrolimus, P < 0.001), while the recipients with grafts from high expressers or with grafts carrying at least one copy of the functional CYP3A5*1 allele required an increase (by about 50% [12.8-13.8 mg kg(-1)] for ciclosporin and 100% [0.21 mg kg(-1) ] for tacrolimus, P < 0.001) of the initial CNI dose for achieving target blood concentrations. CONCLUSIONS: Donor livers' CYP3A-status, taking both CYP3A5 allelic variations and CYP3A4 expression into account, can better identify the risk of CNI over- or underexposure, and may contribute to the avoidance of misdosing-induced graft injury in the early post-operative period. PMID- 26271662 TI - Tumor Lysis Syndrome in an Unusual Metastatic Pancreatic Neuroendocrine Tumor with Ectopic ACTH Secretion. PMID- 26271663 TI - Etiology, Diagnosis and Treatment of Tendinous Knee Extensor Mechanism Injuries. AB - BACKGROUND AND AIMS: Quadriceps and patella tendon ruptures are uncommon injuries often resulting from minor trauma typically consisting of an eccentric contraction of the quadriceps muscle. Since rupture of a healthy tendon is very rare, such injuries usually represent the end stage of a long process of chronic tendon degeneration and overuse. This review aims to give an overview of the current understanding of the pathophysiology, diagnostic principles, and recommended treatment protocols as supported by the literature and institutional experience. MATERIAL AND METHODS: A non-systematic review of the current literature on the subject was conducted and reflected against the current practice in our level 1 trauma center. RESULTS AND CONCLUSION: Risk factors for patella and quadriceps tendon rupture include increasing age, repetitive micro trauma, genetic predisposition, and systemic diseases, as well as certain medications. Diagnosis is based on history and clinical findings, but can be complemented by ultrasound or magnetic resonance imaging. Accurate diagnosis at an early stage is of utmost importance since delay in surgical repair of over 3 weeks results in significantly poorer outcomes. Operative treatment of acute ruptures yields good clinical results with low complication rates. Use of longitudinal transpatellar drill holes is the operative method of choice in the majority of acute cases. In chronic ruptures, tendon augmentation with auto- or allograft should be considered. Postoperative treatment protocols in the literature range from early mobilization with full weight bearing to cast immobilization for up to 12 weeks. Respecting the biology of tendon healing, we advocate the use of a removable knee splint or orthotic with protected full weight bearing and limited passive mobilization for 6 weeks. PMID- 26271664 TI - Genetic and biochemical characterization of arginine biosynthesis in Sinorhizobium meliloti 1021. AB - L-Ornithine production in the alfalfa microsymbiont Sinorhizobium meliloti occurs as an intermediate step in arginine biosynthesis. Ornithine is required for effective symbiosis but its synthesis in S. meliloti has been little studied. Unlike most bacteria, S. meliloti 1021 is annotated as encoding two enzymes producing ornithine: N-acetylornithine (NAO) deacetylase (ArgE) hydrolyses NAO to acetate and ornithine, and glutamate N-acetyltransferase (ArgJ) transacetylates l glutamate with the acetyl group from NAO, forming ornithine and N-acetylglutamate (NAG). NAG is the substrate for the second step of arginine biosynthesis catalysed by NAG kinase (ArgB). Inactivation of argB in strain 1021 resulted in arginine auxotrophy. The activity of purified ArgB was significantly inhibited by arginine but not by ornithine. The purified ArgJ was highly active in NAO deacetylation/glutamate transacetylation and was significantly inhibited by ornithine but not by arginine. The purified ArgE protein (with a 6His-Sumo affinity tag) was also active in deacetylating NAO. argE and argJ single mutants, and an argEJ double mutant, are arginine prototrophs. Extracts of the double mutant contained aminoacylase (Ama) activity that deacetylated NAO to form ornithine. The purified products of three candidate ama genes (smc00682 (hipO1), smc02256 (hipO2) and smb21279) all possessed NAO deacetylase activity. hipO1 and hipO2, but not smb21279, expressed in trans functionally complemented an Escherichia coli DeltaargE : : Km mutant. We conclude that Ama activity accounts for the arginine prototrophy of the argEJ mutant. Transcriptional assays of argB, argE and argJ, fused to a promoterless gusA gene, showed that their expression was not significantly affected by exogenous arginine or ornithine. PMID- 26271665 TI - Erratum to: Thioridazine specifically sensitizes drug-resistant cancer cells through highly increase in apoptosis and P-gp inhibition. PMID- 26271666 TI - Compound 13, an alpha1-selective small molecule activator of AMPK, potently inhibits melanoma cell proliferation. AB - It is vital to develop new therapeutic agents for the treatment of melanoma. In the current study, we studied the potential effect of Compound 13 (C13), a novel alpha1-selective AMP-activated protein kinase (AMPK) activator, in melanoma cells. We showed that C13 exerted mainly cytostatic, but not cytotoxic activities in melanoma cells. C13 potently inhibited proliferation in melanoma cell lines (A375, OCM-1 and B16), but not in B10BR melanocytes. Meanwhile, the AMPK activator inhibited melanoma cell cycle progression by inducing G1-S arrest. Significantly, we failed to detect significant melanoma cell death or apoptosis after the C13 treatment. For the mechanism study, we showed that C13 activated AMPK and inhibited mammalian target of rapamycin complex 1 (mTORC1) signaling in melanoma cells through interaction with the alpha1 subunit. Short hairpin RNA (shRNA)-mediated knockdown of AMPKalpha1 not only blocked C13-mediated AMPK activation but also abolished its antiproliferative activity against melanoma cells. Together, these results show that C13 inhibits melanoma cell proliferation through activating AMPK signaling. Our data suggest that C13 along with other small molecular AMPK activators may be beneficial for patients with melanoma. PMID- 26271668 TI - MSX1 inhibits cell migration and invasion through regulating the Wnt/beta-catenin pathway in glioblastoma. AB - Glioblastoma is a type of primary brain tumor with poor prognosis. The hallmark phenotype of glioblastoma is its aggressive invasion. Understanding the molecular mechanism of the invasion behavior of glioblastoma is essential for the development of effective treatment of the disease. In our present study, we found that the expression levels of a homeobox transcription factor, MSX1, were significantly reduced in glioblastoma compared to normal brain tissues. The levels of MSX1 in glioblastoma tissues were also correlated with the survival of the patients. In cultured glioblastoma cells, MSX1 was a negative regulator of cell migration and invasion. Loss of MSX1 enhanced cell migration and induced mesenchymal transition as characterized by the downregulation of E-cadherin and the upregulation of N-cadherin. Overexpression of MSX1 on the other hand led to the inhibition of both cell migration and mesenchymal transition. We also found that MSX1 was able to inhibit the Wnt/beta-catenin signaling pathway, and that the ability to regulate the Wnt/beta-catenin signaling pathway is critical for MSX1 to suppress glioblastoma cell migration and invasion. PMID- 26271671 TI - Interactions Between a Belowground Herbivore and Primary and Secondary Root Metabolites in Wild Cabbage. AB - Plants are attacked by both above- and belowground herbivores. Toxic secondary compounds are part of the chemical defense arsenal of plants against a range of antagonists, and are subject to genetic variation. Plants also produce primary metabolites (amino acids, nutrients, sugars) that function as essential compounds for growth and survival. Wild cabbage populations growing on the Dorset coast of the UK exhibit genetically different chemical defense profiles, even though they are located within a few kilometers of each other. As in other Brassicaceae, the defensive chemicals in wild cabbages constitute, among others, secondary metabolites called glucosinolates. Here, we used five Dorset populations of wild cabbage to study the effect of belowground herbivory by the cabbage root fly on primary and secondary chemistry, and whether differences in chemistry affected the performance of the belowground herbivore. There were significant differences in total root concentrations and chemical profiles of glucosinolates, amino acids, and sugars among the five wild cabbage populations. Glucosinolate concentrations not only differed among the populations, but also were affected by root fly herbivory. Amino acid and sugar concentrations also differed among the populations, but were not affected by root fly herbivory. Overall, population related differences in plant chemistry were more pronounced for the glucosinolates than for amino acids and sugars. The performance of the root herbivore did not differ among the populations tested. Survival of the root fly was low (<40%), suggesting that other belowground factors may override potential differences in effects related to primary and secondary chemistry. PMID- 26271667 TI - The long noncoding RNA, EGFR-AS1, a target of GHR, increases the expression of EGFR in hepatocellular carcinoma. AB - LncRNA has provided an important new perspective regarding gene regulation. Both the expression and activation of EGFR have been proven to be under the tight control of the GHR pathway. EGFR-AS1 has been found to inhibit the expression of EGFR. GHR-siRNA and EGFR-AS1-siRNA were transfected into HCC cell lines, and a series of WB, q-PCR, and IF experiments was conducted to evaluate whether EGFR AS1 participated in the regulation of GHR and EGFR. We found that impeded expression of GHR decreased the expression of EGFR and EGFR-AS1 in vivo and in vitro. Then, it was verified that EGFR and EGFR-AS1 were relatively upregulated in HCC tissue, and they were significantly related to some clinical characteristics and patient prognosis. Furthermore, EGFR-AS1 was determined to promote HCC development by improving the ability of invasion and proliferation of HCC cells in vitro, and it was also found to affect the cell cycle. Our study identified that EGFR-AS1 may promote HCC genesis and development. EGFR-AS1 may act as a prognostic factor in HCC. More importantly, we observed that the inhibition of EGFR-AS1 in HCC cells significantly impeded cell proliferation and invasion in vivo, which might provide a potential possibility for targeted therapy of HCC. PMID- 26271669 TI - The involvement of survivin in insulin-like growth factor 1-induced epithelial mesenchymal transition in gastric cancer. AB - It has been identified that insulin-like growth factor 1 (IGF-1) activated various pathways of the epithelial-mesenchymal transition (EMT) in a couple of tumors. At the same time, survivin is implicated in EMT of gastric cancer (GC). To date, the impact of survivin on IGF-1-mediated EMT of GC has not been featured. In this work, we used the immunohistochemistry and molecular and cellular experiments to investigate the existence and significance of IGF-1 and survivin. Our findings revealed that survivin protein can be observed in majority of samples in all GC samples. Importantly, survivin expression has an obvious association with GC stage, and metastasis. In vitro, GC cell line BGC823 was treated with different concentrations of IGF-1, resulting in the activation of p ERK, p-AKT, survivin, and the expression of EMT biomarkers, including N-cadherin, MMP2, and Snail. However, the silencing of survivin eradicated the expression IGF 1-induced EMT biomarkers and affected the migration and invasion of BGC823 cells. In conclusion, IGF-1 signaling activated survivin expression and controlled the expression of EMT biomarkers in the development of GC. This study lays a new stage for the molecular therapy of GC patients in the clinical treatment. PMID- 26271673 TI - The Scent Glands of the Neotropical Harvestman Discocyrtus pectnifemur: Morphology, Behavior and Chemistry. AB - Harvestmen have a pair of scent glands that open through ozopores. The literature suggests a link between the morphology of the ozopore area and the emission of a defensive secretion. A previous study on a species that aggregates in open areas, where individuals are probably more easily spotted by predators, showed that this defensive secretion causes conspecifics to flee. However, it is unknown whether this behavior occurs in species that aggregate in sheltered areas, where prey are harder to find. Herein, we describe the morphology of the ozopore area, the mode of emission of the defensive secretion, and its chemical composition in the harvestman Discocyrtus pectinifemur. We also tested if the defensive secretion is used as an alarm pheromone. We found that D. pectinifemur releases the defensive secretion in different ways, one of them being as a jet. Emission as a jet contrasts with that known for all congeners previously studied, and is in accord with the expected morphology of the ozopore. We found that the defensive secretion of D. pectinifemur does not function as an alarm pheromone. The composition of the defensive secretion, a mixture of quinones, is congruent with those already described for the clade that includes Discocyrtus. Our results support the link between the morphology of the scent glands area and the emission behavior of the defensive secretion, and they suggest that the alarm pheromone function in harvestmen may be dependent on ecological factors. PMID- 26271672 TI - Identification of the Female-Produced Sex Pheromone of the Leafminer Holocacista capensis Infesting Grapevine in South Africa. AB - We report the first identification of a sex pheromone in a heliozelid moth, Holocacista capensis van Nieukerken & Geertsema. This leafminer recently infested grapevine in South Africa. Compared to solvent extraction of pheromone glands, solid phase microextraction (SPME) proved to be highly effective for collection of the pheromone from calling females. The volatiles collected by SPME were analyzed by gas chromatography with electroantennographic detection (GC/EAD). Three compounds eliciting electrophysiological activity from the male antenna were identified as (Z)-5-tetradecenal, (Z)-7-tetradecenal, and (Z)-9-hexadecenal by coupled gas chromatography-mass spectrometry (GC/MS). GC/MS analysis of dimethyldisulphide (DMDS) derivatives of fatty acyl moieties in pheromone gland extracts confirmed the presence of the corresponding putative pheromone precursors with double bonds in the same position and with Z geometry. Field trapping experiments in a South African vineyard confirmed that both (Z)-5 tetradecenal and (Z)-7-tetradecenal are essential for the attraction of male H. capensis, whereas addition of (Z)-9-hexadecenal to the blend did not affect the attractiveness. The composition of the pheromone is discussed in relation to the phylogeny of this family of moths. PMID- 26271670 TI - Determination of Nitrite in Whole Blood by High-Performance Liquid Chromatography with Electrochemical Detection and a Case of Nitrite Poisoning. AB - Although nitrite is widely used in meat processing, it is a major toxicity hazard to children and is responsible for the blue-baby syndrome. A simple and effective method to determine nitrite in whole blood has been devised using ion chromatography with suppressed conductivity detection. The blood sample was deproteinized by adding acetonitrile and purified with mini-cartridges to remove hydrophobic compounds, chloride ions, and metal ions. An aliquot of the filtrate was injected onto the ion chromatography. The retention time for nitrite was 13.8 min and the detection limit of nitrite in whole blood was 0.4 MUmol/L. The calibration curve was linear (r(2) = 0.9999) over the concentration working range. The blood nitrite concentration of a victim who attempted suicide by ingesting sodium nitrite powder was determined using the present method. The basal levels for nitrite in human blood was determined with 7.1 +/- 0.9 MUmol/L (n = 12). PMID- 26271674 TI - (7E,11E)-3,5,9,11-Tetramethyltridecadienal: Sex Pheromone of the Strepsipteran Xenos peckii. AB - Xenos peckii is a strepsipteran parasitoid of the common North American paper wasp, Polistes fuscatus. Mate-seeking X. peckii males respond to a long-range sex pheromone emitted by the female, which remains permanently embedded within the abdomen of a mobile host wasp. During peak pheromone signalling, we excised the female from her host, severed the cephalothorax containing the pheromone gland, extracted it in hexane, and analyzed aliquots of combined extracts by coupled gas chromatographic-electroantennographic detection (GC-EAD). These analyses revealed a candidate pheromone component (CPC) that consistently elicited strong responses from male antennae. We identified the CPC as (7E,11E)-3,5,9,11 tetramethyltridecadienal based on its retention indices (RI) on three GC-columns, RI inter-column differentials, mass and NMR spectra, and synthesis of an authentic standard that matched the GC-retention and spectrometric characteristics of the CPC. For a field experiment, we prepared (7E,11E) 3,5,9R,11-tetramethyltridecadienal and (7E,11E)-3,5,9S,11 tetramethyltridecadienal. Xenos peckii males were caught in traps baited with either compound singly or a 1:1 mixture of the two but not in unbaited control traps. The sex pheromone of X. peckii resembles that reported for the strepsipterans Stylops mellittae and S. muelleri, (R,R,R)-3,5,9 trimethyldodecanal, suggesting a common biosynthetic pathway across taxonomic genera. PMID- 26271676 TI - Supporting rehabilitation in developing countries. PMID- 26271675 TI - HSP90 Inhibitor-SN-38 Conjugate Strategy for Targeted Delivery of Topoisomerase I Inhibitor to Tumors. AB - The clinical benefits of chemotherapy are commonly offset by insufficient drug exposures, narrow safety margins, and/or systemic toxicities. Over recent decades, a number of conjugate-based targeting approaches designed to overcome these limitations have been explored. Here, we report on an innovative strategy that utilizes HSP90 inhibitor-drug conjugates (HDC) for directed tumor targeting of chemotherapeutic agents. STA-12-8666 is an HDC that comprises an HSP90 inhibitor fused to SN-38, the active metabolite of irinotecan. Mechanistic analyses in vitro established that high-affinity HSP90 binding conferred by the inhibitor backbone could be exploited for conjugate accumulation within tumor cells. In vivo modeling showed that the HSP90 inhibitor moiety was required for selective retention of STA-12-8666, and this enrichment promoted extended release of active SN-38 within the tumor compartment. Indeed, controlled intratumoral payload release by STA-12-8666 contributed to a broad therapeutic window, sustained biomarker activity, and remarkable degree of efficacy and durability of response in multiple cell line and patient-derived xenograft models. Overall, STA 12-8666 has been developed as a unique HDC agent that employs a distinct mechanism of targeted drug delivery to achieve potent and sustained antitumor effects. These findings identify STA-12-8666 as a promising new candidate for evaluation as novel anticancer therapeutic. PMID- 26271677 TI - Kids are not little adults: what MET threshold captures sedentary behavior in children? AB - PURPOSE: The study compares MET-defined cutpoints used to classify sedentary behaviors in children using a simulated free-living design. METHODS: A sample of 102 children (54 boys and 48 girls; 7-13 years) completed a set of 12 activities (randomly selected from a pool of 24 activities) in a random order. Activities were predetermined and ranged from sedentary to vigorous intensities. Participant's energy expenditure was measured using a portable indirect calorimetry system, Oxycon mobile. Measured minute-by-minute VO2 values (i.e., ml/kg/min) were converted to an adult- or child-MET value using the standard 3.5 ml/kg/min or the estimated child resting metabolic rate, respectively. Classification agreement was examined for both the "standard" (1.5 adult-METs) and an "adjusted" (2.0 adult-METs) MET-derived threshold for classifying sedentary behavior. Alternatively, we also tested the classification accuracy of a 1.5 child-MET threshold. Classification accuracy of sedentary activities was evaluated relative to the predetermined intensity categorization using receiver operator characteristic curves. RESULTS: There were clear improvements in the classification accuracy for sedentary activities when a threshold of 2.0 adult METs was used instead of 1.5 METs (Se1.5 METs = 4.7%, Sp1.5 METs = 100.0%; Se2.0 METs = 36.9%, Sp2.0 METs = 100.0 %). The use of child-METs while maintaining the 1.5 threshold also resulted in improvements in classification (Se = 45.1%, Sp = 100.0%). CONCLUSION: Adult-MET thresholds are not appropriate for children when classifying sedentary activities. Classification accuracy for identifying sedentary activities was improved when either an adult-MET of 2.0 or a child-MET of 1.5 was used. PMID- 26271678 TI - Ventilatory responses to prolonged exercise with heavy load carriage. AB - PURPOSE: The purpose of this experiment was to study breathing pattern and operating lung volume during 45 min of exercise with a heavy backpack (25 kg) and examine the effect of this exercise on respiratory muscle strength. METHODS: Fifteen males completed randomly ordered graded exercise tests on a treadmill with and without a correctly sized and fitted 25 kg pack. Subsequently, each subject completed, in random order, on separate days, 45 min of treadmill walking with and without the pack. Oxygen demand was matched between conditions (loaded: 3.01 +/- 0.11 and unloaded 3.02 +/- 0.11 L min(-1)). RESULTS: With load, breathing frequency (f B) and minute ventilation increased by 21.7 and 15.1 % (P < 0.05), respectively, while tidal volume (V T) and end-inspiratory lung volume (EILV) were reduced by 6.3 and 6.4% (P < 0.05), respectively, compared to unloaded. Following loaded exercise, maximal inspiratory pressure decreased by 6.7% (P < 0.05) with no change in maximal expiratory pressure. No changes in maximal inspiratory or expiratory pressures were observed following unloaded exercise. Despite equivalent oxygen demand, perceived exercise stress and breathing discomfort was higher (P < 0.05) in the loaded condition. CONCLUSIONS: The mechanical disadvantage placed on the respiratory system during exercise with a heavy pack led to compensatory changes in breathing pattern and EILV, and a reduction in maximal inspiratory pressure post-exercise. We suggest that in an attempt to minimize the work of breathing, subjects adopted a shallow and frequent breathing pattern. However, this pattern increased deadspace and minute ventilation, which likely contributed to altered perceptions of exercise stress and breathing discomfort. PMID- 26271679 TI - DaPeCa-2: Implementation of fast-track clinical pathways for penile cancer shortens waiting time and accelerates the diagnostic process--A comparative before-and-after study in a tertiary referral centre in Denmark. AB - OBJECTIVE: The aim of this study was to examine the feasibility and impact of a fast-track referral pathway on clinical time intervals in penile cancer. MATERIALS AND METHODS: This observational study from a tertiary referral centre included 263 patients diagnosed before and after the introduction of an intervention to reduce clinical time intervals, the Cancer Patient Pathway (CPP). The CPP included fast-track referral and set time-frames for units participating in cancer diagnosis and treatment, and was introduced for penile cancer in Denmark on 1 January 2009. Median time intervals (in calendar days) with interquartile range were the main outcome measure. RESULTS: A trend towards reduction was observed in all clinical time intervals, with a statistically significant reduction in the system interval (p = 0.01) and tertiary centre interval (p < 0.0001). The proportion of patients treated within the maximum accepted time-frame of 37 days after referral steadily increased after implementation of the CPP. In particular, unjustified waiting time was reduced significantly. This was mainly achieved through pre-booking of appointments and diagnostic time slots by a dedicated clinical coordinator. CONCLUSIONS: To the authors' knowledge, this is the first study examining the feasibility and impact of an intervention to reduce clinical time intervals in penile cancer. The Danish CPP was successful in reducing system and tertiary centre intervals. Future interventions need to address the long patient interval. Longer follow-up is needed to study the impact of CPP on mortality. PMID- 26271680 TI - Seizure ending signs in patients with dyscognitive focal seizures. AB - AIM: Signs indicating the end of a focal seizure with loss of awareness and/or responsiveness but without progression to focal or generalized motor symptoms are poorly defined and can be difficult to determine. Not recognizing the transition from ictal to postictal behaviour can affect seizure reporting accuracy by family members and may lead to delayed or a lack of examination during EEG monitoring, erroneous seizure localization and inadequate medical intervention for prolonged seizure duration. METHODS: Our epilepsy monitoring unit database was searched for focal seizures without secondary generalization for the period from 2007 to 2011. The first focal seizure in a patient with loss of awareness and/or responsiveness and/or behavioural arrest, with or without automatisms, was included. Seizures without objective symptoms or inadequate video-EEG quality were excluded. RESULTS: A total of 67 patients were included, with an average age of 41.7 years. Thirty-six of the patients had seizures from the left hemisphere and 29 from the right. All patients showed an abrupt change in motor activity and resumed contact with the environment as a sign of clinical seizure ending. Specific ending signs (nose wiping, coughing, sighing, throat clearing, or laughter) were seen in 23 of 47 of temporal lobe seizures and 7 of 20 extra-temporal seizures. CONCLUSIONS: Seizure ending signs are often subtle and the most common finding is a sudden change in motor activity and resumption of contact with the environment. More distinct signs, such as nose wiping, coughing or throat clearing, are not specific to temporal lobe onset. A higher proportion of seizures during sleep went unexamined, compared to those during wakefulness. This demonstrates that seizure semiology can be very subtle and arousals from sleep during monitoring should alert staff. Patient accounts of seizure frequency appear to be unreliable and witness reports need to be taken into account. [Published with video sequences]. PMID- 26271681 TI - Rising to the challenge: acute stress appraisals and selection centre performance in applicants to postgraduate specialty training in anaesthesia. AB - The ability to work under pressure is a vital non-technical skill for doctors working in acute medical specialties. Individuals who evaluate potentially stressful situations as challenging rather than threatening may perform better under pressure and be more resilient to stress and burnout. Training programme recruitment processes provide an important opportunity to examine applicants' reactions to acute stress. In the context of multi-station selection centres for recruitment to anaesthesia training programmes, we investigated the factors influencing candidates' pre-station challenge/threat evaluations and the extent to which their evaluations predicted subsequent station performance. Candidates evaluated the perceived stress of upcoming stations using a measure of challenge/threat evaluation-the cognitive appraisal ratio (CAR)-and consented to release their demographic details and station scores. Using regression analyses we determined which candidate and station factors predicted variation in the CAR and whether, after accounting for these factors, the CAR predicted candidate performance in the station. The CAR was affected by the nature of the station and candidate gender, but not age, ethnicity, country of training or clinical experience. Candidates perceived stations involving work related tasks as more threatening. After controlling for candidates' demographic and professional profiles, the CAR significantly predicted station performance: 'challenge' evaluations were associated with better performance, though the effect was weak. Our selection centre model can help recruit prospective anaesthetists who are able to rise to the challenge of performing in stressful situations but results do not support the direct use of challenge/threat data for recruitment decisions. PMID- 26271682 TI - Label-Free Electrochemiluminescent Immunosensor for Detection of Carcinoembryonic Antigen Based on Nanocomposites of GO/MWCNTs-COOH/Au@CeO2. AB - A high-sensitivity electrochemiluminescence (ECL) sensor was conducted to detect carcinoembryonic antigen (CEA). Nanocomposites of graphene oxide/carboxylated multiwall carbon nanotubes/gold/cerium oxide nanoparticles (GO/MWCNTs COOH/Au@CeO2) were used as antibody carriers and sensing platforms to modify on glassy carbon electrodes (GCE). CeO2 nanoparticles were first exploited as an ECL luminescent material and the possible ECL mechanism was proposed in this work. GO/MWCNTs-COOH was used as a loading matrix for CeO2 nanoparticles because of the superior conductivity and large specific surface area. Au nanoparticles were further deposited on this matrix to attach anti-CEA and enhance the sensitivity of immunosensor. The proposed sensing platform showed excellent cathodic ECL performance and sensitive response to CEA. The effects of experimental conditions on the ECL performance were investigated. The proposed immunosensor showed the broad linear range (0.05-100 ng/mL) and the low detection limit (LOD, 0.02 ng/mL, signal-to-noise ratio = 3) according to the selected experimental conditions. The excellent analysis performance for determination of CEA in the human serum samples simplied this immunosensor displayed high sensitivity and excellent repeatability. More importantly, this conducted immunosensor broadens the use scope of CeO2 nanoparticles. PMID- 26271685 TI - Prone positioning improves oxygenation in spontaneously breathing nonintubated patients with hypoxemic acute respiratory failure: A retrospective study. AB - PURPOSE: Prone positioning (PP) improves oxygenation and outcome of patients with acute respiratory distress syndrome undergoing invasive ventilation. We evaluated feasibility and efficacy of PP in awake, non-intubated, spontaneously breathing patients with hypoxemic acute respiratory failure (ARF). MATERIAL AND METHODS: We retrospectively studied non-intubated subjects with hypoxemic ARF treated with PP from January 2009 to December 2014. Data were extracted from medical records. Arterial blood gas analyses, respiratory rate, and hemodynamics were retrieved 1 to 2 hours before pronation (step PRE), during PP (step PRONE), and 6 to 8 hours after resupination (step POST). RESULTS: Fifteen non-intubated ARF patients underwent 43 PP procedures. Nine subjects were immunocompromised. Twelve subjects were discharged from hospital, while 3 died. Only 2 maneuvers were interrupted, owing to patient intolerance. No complications were documented. PP did not alter respiratory rate or hemodynamics. In the subset of procedures during which the same positive end expiratory pressure and Fio2 were utilized throughout the pronation cycle (n=18), PP improved oxygenation (Pao2/Fio2 124+/-50 mmHg, 187+/ 72 mmHg, and 140+/-61 mmHg, during PRE, PRONE, and POST steps, respectively, P<.001), while pH and Paco2 were unchanged. CONCLUSIONS: PP was feasible and improved oxygenation in non-intubated, spontaneously breathing patients with ARF. PMID- 26271684 TI - A combined systems and structural modeling approach repositions antibiotics for Mycoplasma genitalium. AB - Bacteria are increasingly resistant to existing antibiotics, which target a narrow range of pathways. New methods are needed to identify targets, including repositioning targets among distantly related species. We developed a novel combination of systems and structural modeling and bioinformatics to reposition known antibiotics and targets to new species. We applied this approach to Mycoplasma genitalium, a common cause of urethritis. First, we used quantitative metabolic modeling to identify enzymes whose expression affects the cellular growth rate. Second, we searched the literature for inhibitors of homologs of the most fragile enzymes. Next, we used sequence alignment to assess that the binding site is shared by M. genitalium, but not by humans. Lastly, we used molecular docking to verify that the reported inhibitors preferentially interact with M. genitalium proteins over their human homologs. Thymidylate kinase was the top predicted target and piperidinylthymines were the top compounds. Further work is needed to experimentally validate piperidinylthymines. In summary, combined systems and structural modeling is a powerful tool for drug repositioning. PMID- 26271686 TI - Epidemiological trends in invasive mechanical ventilation in the United States: A population-based study. AB - PURPOSE: Epidemiological trends for invasive mechanical ventilation (IMV) have not been clearly defined. We sought to define trends for IMV in the United States and assess for disease-specific variation for 3 common causes of respiratory failure: pneumonia, heart failure (HF), and chronic obstructive pulmonary disease (COPD). METHODS: We calculated national estimates for utilization of nonsurgical IMV cases from the Nationwide Inpatient Sample from 1993 to 2009 and compared trends for COPD, HF, and pneumonia. RESULTS: We identified 8309344 cases of IMV from 1993 to 2009. Utilization of IMV for nonsurgical indications increased from 178.9 per 100000 in 1993 to 310.9 per 100000 US adults in 2009. Pneumonia cases requiring IMV showed the largest increase (103.6%), whereas COPD cases remained relatively stable (2.5% increase) and HF cases decreased by 55.4%. Similar demographic and clinical changes were observed for pneumonia, COPD, and HF, with cases of IMV becoming younger, more ethnically diverse, and more frequently insured by Medicaid. Outcome trends for patients differed based on diagnosis. Adjusted hospital mortality decreased over time for cases of pneumonia (odds ratio [OR] per 5 years, 0.89; 95% confidence interval [CI], 0.88-0.90) and COPD (OR per 5 years, 0.97; 95% CI, 0.97-0.98) but increased for HF (OR per 5 years, 1.10; 95% CI, 1.09-1.12). CONCLUSION: Utilization of IMV in the US increased from 1993 to 2009 with a decrease in overall mortality. However, trends in utilization and outcomes of IMV differed markedly based on diagnosis. Unlike favorable outcome trends in pneumonia and COPD, hospital mortality for HF has not improved. Further studies to investigate the outcome gap between HF and other causes of respiratory failure are needed. PMID- 26271687 TI - Revisiting endotracheal self-extubation in the surgical and trauma intensive care unit: Are they all fine? AB - OBJECTIVES: Endotracheal self-extubation (ESE) is a serious health care concern. We designed this study to test our hypothesis that not all patients with ESE are successful in spontaneous breathing and reintubation has negative impact on outcomes. METHODS: Data on all 39 patients of ESE in our surgical and trauma intensive care unit (ICU) in 2012 were prospectively collected and retrospectively analyzed. RESULTS: There were 42 episodes of ESE in 39 of 939 intubated patients (frequency, 4.0%), with 54% of events requiring reintubation. Pre-ESE positive end-expiratory pressure was higher and Pao2/fraction of inspired oxygen ratio was lower, and the post-ESE respiration rate was higher in the reintubated group. On univariate analysis, weaning and spontaneous breathing trial before ESE were favorable predictors for nonreintubation. Multivariate regression analysis demonstrated that agitation before ESE was an independent predictor of reintubation. The need for reintubation was associated with increased risk of pulmonary infectious complications, ventilator days, the need for tracheostomy, and ICU and hospital LOS. The financial costs for ventilator days and ICU rooms were significantly higher in patients with reintubation. CONCLUSION: Not all patients were fine after ESE. We have not decreased the frequency of ESE or improved outcomes if the patients were reintubated. The need for reintubation was not only associated with a high pulmonary complication rate but also prolonged duration on mechanical ventilation and hospital/ICU stay and increased the hospital costs. PMID- 26271688 TI - Trees and shrubs differ biomechanically. PMID- 26271690 TI - Academy of Nutrition and Dietetics: Standards of Practice and Standards of Professional Performance for Registered Dietitian Nutritionists (Competent, Proficient, and Expert) in Public Health and Community Nutrition. AB - The need and demand for population-level disease prevention has increased, especially with the passage of the Affordable Care Act, a worldwide increase in obesity and chronic disease, and a global emphasis on preventative health care that includes behavioral, environmental, and policy interventions. In response to these evolving needs, the Public Health and Community Nutrition Dietetic Practice Group, with guidance from the Academy of Nutrition and Dietetics Quality Management Committee, has developed Standards of Practice and Standards of Professional Performance as tools for registered dietitian nutritionists (RDNs) currently in practice or interested in working in public health and community nutrition, to assess their current skill levels and to identify areas for professional development. The Standards of Practice address the four steps of the Nutrition Care Process for community and public health RDNs, which are assessment, diagnosis, intervention, and evaluation/monitoring. The Standards of Professional Performance consist of the following six domains of professional performance for community and public health RDNs: Quality in Practice, Competence and Accountability, Provision of Services, Application of Research, Communication and Application of Knowledge, and Utilization and Management of Resources. Within each standard, specific indicators provide measurable action statements that illustrate the ways in which RDNs can address client and population nutrition and health. The indicators describe three skill levels (competent, proficient, and expert) for RDNs. These tools highlight the unique scope of expertise that RDNs provide to the field of public health and community nutrition. PMID- 26271692 TI - Remote Nutrition Counseling: Considerations in a New Channel for Client Communication. PMID- 26271693 TI - GM crops and the rat digestive tract: A critical review. PMID- 26271689 TI - Comparative Efficacy of Intracoronary Allogeneic Mesenchymal Stem Cells and Cardiosphere-Derived Cells in Swine with Hibernating Myocardium. AB - RATIONALE: Allogeneic bone marrow-derived mesenchymal stem cells (MSCs) and cardiosphere-derived cells (CDCs) have each entered clinical trials, but a direct comparison of these cell types has not been performed in a large animal model of hibernating myocardium. OBJECTIVE: Using completely blinded methodology, we compared the efficacy of global intracoronary allogeneic MSCs (icMSCs, ~35*10(6)) and CDCs (icCDCs, ~35*10(6)) versus vehicle in cyclosporine-immunosuppressed swine with a chronic left anterior descending coronary artery stenosis (n=26). METHODS AND RESULTS: Studies began 3 months after instrumentation when wall thickening was reduced (left anterior descending coronary artery % wall thickening [mean+/-SD], 38+/-11% versus 83+/-26% in remote; P<0.01) and similar among groups. Four weeks after treatment, left anterior descending coronary artery % wall thickening increased similarly after icCDCs and icMSCs, whereas it remained depressed in vehicle-treated controls (icMSCs, 51+/-13%; icCDCs, 51+/ 17%; vehicle, 34+/-3%, treatments P<0.05 versus vehicle). There was no change in myocardial perfusion. Both icMSCs and icCDCs increased left anterior descending coronary artery myocyte nuclear density (icMSCs, 1601+/-279 nuclei/mm(2); icCDCs, 1569+/-294 nuclei/mm(2); vehicle, 973+/-181 nuclei/mm(2); treatments P<0.05 versus vehicle) and reduced myocyte diameter (icMSCs, 16.4+/-1.5 MUm; icCDCs, 16.8+/-1.2 MUm; vehicle, 20.2+/-3.7 MUm; treatments P<0.05 versus vehicle) to the same extent. Similar changes in myocyte nuclear density and diameter were observed in the remote region of cell-treated animals. Cell fate analysis using Y chromosome fluorescent in situ hybridization demonstrated rare cells from sex mismatched donors. CONCLUSIONS: Allogeneic icMSCs and icCDCs exhibit comparable therapeutic efficacy in a large animal model of hibernating myocardium. Both cell types produced equivalent increases in regional function and stimulated myocyte regeneration in ischemic and remote myocardium. The activation of endogenous myocyte proliferation and regression of myocyte cellular hypertrophy support a common mechanism of cardiac repair. PMID- 26271691 TI - Food Environment Interventions to Improve the Dietary Behavior of Young Adults in Tertiary Education Settings: A Systematic Literature Review. AB - The current obesity-promoting food environment, typified by highly accessible unhealthy foods and drinks, may lead to an increased risk of chronic disease, particularly within young adults. A number of university-based intervention trials have been conducted in the United States and Europe to improve the food environment in this setting. However, there are no systematic reviews focusing on these interventions conducted exclusively in tertiary education settings. Our objective was to conduct a systematic literature review evaluating food environment interventions targeting dietary behavior in young adults in college and university settings. Eight databases were searched for randomized controlled trials, pre- and postintervention studies, quasiexperimental studies, cross sectional studies, and other nonexperimental studies from 1998 to December 2014 that were conducted in tertiary education settings (ie, colleges and universities). Studies that evaluated a food environment intervention and reported healthier food choices, reductions in unhealthy food choices, nutrition knowledge, and/or food and drink sales as primary outcomes were included. Fifteen studies of high (n=5), medium (n=7), and poor quality (n=3) met the inclusion criteria, 13 of which showed positive improvements in outcome measures. Information relating to healthy foods through signage and nutrition labels (n=10) showed improvements in outcomes of interest. Increasing the availability of healthy foods (n=1) and decreasing the portion size of unhealthy foods (n=2) improved dietary intake. Price incentives and increased availability of healthy foods combined with nutrition information to increase purchases of healthy foods (n=2) were identified as having a positive effect on nutrition-related outcomes. Potentially useful interventions in tertiary education settings were nutrition messages/nutrient labeling, providing healthy options, and portion size control of unhealthy foods. Price decreases for and the increased availability of healthy options combined with nutrition information resulted in improvements in dietary habits. Additional research comparing the long-term effectiveness of environmental and combinations of environmental interventions on improving health outcomes is warranted. PMID- 26271695 TI - [Age-related enamel features in healthy and decayed teeth]. AB - The aim of the study was to identify the age-related variety of structural features of healthy and decayed enamel. The study included 125 people divided in subgroups according to age with both intact teeth and teeth affected by caries. Age-related differences were observed and the development of compensatory reactions was found in 43.3% of caries sites. PMID- 26271694 TI - [Dynamics of osteogenesis after inoculation of autogenic mesenchymal stem cells of adipose tissue]. AB - Experiment was conducted on 40 rats of Wister line. On the artificially reproduced experimental model autogenic mesenchimal stem cells (MSC) of adipose tissue were inoculated in space between bone autograph of tibia and mandible. MSC wasn't inoculated in the comparison group. Formation of a new bone substance in space between an autograph and mandible bone was observed. It was clear that after 120 days (180 days), there was a statistically significant decline of the area occupied by an immature fibroreticular bone. Described phenomenon, presumably, could be explained as a result of decline of the number of active cells in the population of inoculated MSC according to phenomenon of limited number divisions of cells on telomeres, described by Hayflick L. and Moorhead P.S. PMID- 26271696 TI - [Epidemiology of teeth hypersensitivity]. AB - A clinical examination of 98 patients aged 20 to 75 years was carried out to identifyclinical and epidemiological features of hard tooth tissueshypersensitivity. The survey found out what stimuli (cold, hot, sour, mechanical, chemical) cause the appearance of dental hyperesthesia. The detailed survey of the affected area aimed to determine the presence of dental caries, gingival recession, wedge-shaped defects, erosions, microcracks and chipped enamel, as well as wear of the tooth crown. Forty-threepatients of 98 (43.88%) had tooth sensitivity. Most affected age group was 25-34 years (33%). Among patients studied with hyperesthesia 86% complained of pain. It was establishedthat dental hyperesthesia most often causes an intense, but quickly passing pain response, wherein upon exposure of several types of stimuli. Teeth with high sensitivity showed signs of abrasion (74.1%), most often--on the vestibular surface (44.4%). Patients under 45 years had notable cracks and wedge shaped defects. In patients 45 years and older cracks and increased abrasion of hard dental tissues was seen. PMID- 26271698 TI - [Anatomical rationale for lingual nerve injury prevention during mandibular block]. AB - The topographic and anatomical study of lingual nerve structural features was done. It was revealed that during mandibular anesthesia possible lingual nerve injury can occur if puncture needle is lower than 1 cm. of molars occlusal surface level. The position of the lingual nerve varies withmandible movements. At the maximum open mouth lingual nerve is not mobile and is pressed against the inner surface of the mandibular ramus by the medial pterygoid muscle and the temporal muscle tendon. When closing the mouth to 1.25+/-0.2 cmfrom the physiological maximum, lingual nerve is displaced posteriorly from the internal oblique line of the mandible and gets mobile. On the basis of topographic and anatomic features of the lingual nervestructure the authors recommend the re-do of inferior alveolar nerve block, a semi-closed mouth position or the use the "high block techniques" (Torus anesthesia, Gow-Gates, Vazirani-Akinozi). PMID- 26271699 TI - [Optimization of staged treatment in patients with extensive combined face defects]. AB - Free autotransplantation of revascularized flaps allow reconstructing soft tissue integrity with simultaneous bone defects elimination in patients with extensive combined face defects, but for eligible reconstruction of facial proportions one may need additional surgical procedures. The study included 161 patients who underwent free autotransplantation of revascularized flaps. Main pitfalls of the method are revealed and reviewed in the paper. When corresponding to deformity type free autotransplantation of revascularized flaps results in full functional and esthetic rehabilitation. PMID- 26271697 TI - [Choice of local anesthetic volume at the infiltration anesthesia on the upper jaw]. AB - The aim of this study was to investigate the effect of volume and pressure, at which the solution of local anesthetic is injected into the tissue, on the effectiveness of infiltration anesthesia of the periosteum on the upper jaw. We used the technique of tooth pain sensitivity thresholds. According to the rate of development and the duration of the maximum analgesia effect, the optimum volume for different levels of pressure was determined. The influence of the tissue density at the injection site on the effect criteria of analgesia was demonstrated. PMID- 26271700 TI - [Use of adaptogens for antioxidant system correction in complex treatment of mandibular fractures]. AB - Antioxidatic protection has been studied in 84 patients with mandibular fractures between the ages of 21 and 40; the patients were divided into two groups. Activation of lipid peroxidation in both groups was revealed. The increase of antioxidant's activity system in 37.18% in the main study group that along with traditional treatment received Epsorin was determined. No complications in the main group during the post-surgery period were recorded. PMID- 26271701 TI - [Visual perception of dentition esthetic parameters (part 1)]. AB - The article presents a study on the impact of violations of aesthetic parameters as the inclination of the incisalline, thedislocation of median interincisal line and the width of dental arch on visual perception. Comparison of the data of objective assessment data the subjective assessment of the respondents was conducted. It is proved that all dependencies are linear and can be described by a linear regression equations. A similar method can be used for objective quantitative method for the assessment of aesthetics teeth when you smile before and after dental treatment. PMID- 26271704 TI - [Financing of dental care in the outpatient settings in the system of obligatory medical insurance]. PMID- 26271702 TI - [EMG functional changes in masticatory muscles by elastopositioner use in patients with TMJ dysfunction]. AB - The analysis of the results of EMG studies in patients with TMJ dysfunction was carried out before and after use of elastpositioner "Corrector". The study revealed significant functional disturbances of the masticatory muscles, which were corrected after applying elastpositioner: there was a trend to decreased activity of masseter and temporal muscles, especially in the stage of rest. PMID- 26271703 TI - [Late morphological teeth changes in children after chemotherapy]. AB - BACKGROUND: Teeth changes after chemotherapy are of clinical importance, but no morphological studies were conducted on microscopic level. AIM: To assess morphological changes in teeth developing under chemotherapy. MATERIALS AND METHODS: Twenty-nine adolescents aged 13-16 years that received chemotherapy at the age of 2-13 were included in the study. Teeth morphology was evaluated by means of clinical and radiological data as well as microscopy of extracted teeth (n=13). Thirty healthy children aged 13-16 and 8 teeth extracted for orthodontic reasons served as a control. RESULTS: Chemotherapy has arresting impact on teeth development confirmed by aplasia of germs when influenced on stages I-II (p=0.0001), preliminary apexogenesis resulting in shortened roots in teeth at the later stages of growth and development (p=0.01). Enamel and dentine defects usually located in cervical area are also a specific feature, while caries incidence was not higher when compared to control group. CONCLUSION: Children receiving chemotherapy have high risk of secondary teeth loss because of germs aplasia and extraction of severely decayed teeth. Early diagnostics helps to prevent secondary deformations of dental arches by prompt prosthetic rehabilitation. Root morphology changes should be considered by root canal treatment. PMID- 26271705 TI - [Legal state of dental service in Ryazan region]. AB - Analysis showed that the organizational-legal basis of dental service of the Ryazan region consists of limited liability companies (50.2%) and government budgetary institutions (40.3%). PMID- 26271706 TI - Aflatoxins ingestion and canine mammary tumors: There is an association? AB - The aim of this study was to determine the presence of mycotoxins on dogs feed and to explore the potential association between mycotoxins exposure and the chance of mamary tumors in a case-control study. The study included 256 female dogs from a hospital population, 85 with mammary tumors (case group) and 171 without mammary tumors (control group). An epidemiological questionnaire was applied to both groups, and the data were analyzed by the EpiInfo statistical package. For the study, 168 samples of the feed offered to dogs were analyzed for the presence of aflatoxins, fumonisins and zearalenone by high-performance liquid chromatography. Mycotoxins were found in 79 samples (100%) in the case group and 87/89 (97.8%) in the control group. Mycotoxins were detected in all types of feed, regardless feed quality. Level of aflatoxin B1 (p = 0.0356, OR = 2.74, 95%, CI 1.13 to 6.60), aflatoxin G1 (AFG1) (p = 0.00007, OR = 4.60, 95%, CI = 2.16 to 9.79), and aflatoxin G2 (AFG2) (p = 0.0133, OR = 9.91, 95%, CI 1.21 to 81.15) were statistically higher in case of mammary cancer. In contrast, neutering was a protective factor for mammary cancer (p = 0.0004, OR = 0.32, 95%, CI = 0.17 to 0.60). PMID- 26271708 TI - Re: Gut microbiota depletion from early adolescence in mice: Implications for brain and behaviour. PMID- 26271709 TI - A numerical investigation of the functionality of coronary bifurcation lesions with respect to lesion configuration and stenosis severity. AB - The intervention of coronary bifurcation lesions is associated with higher rates of peri- and post-procedural clinical events compared to the treatment of isolated lesions. Overall, the factors that influence the dynamics of these types of configurations are still not well understood. A geometric multiscale model, consisting of a 3D representation of the left main coronary artery bifurcation and a 0D representation of the rest of the cardiovascular system, was developed. Computational fluid dynamics simulations of the 3D domain were executed by implementing the multiscale algorithm, in order to characterize the functionality of different multilesional configurations as a function of stenosis severity. The investigation found that coronary branch steal has a significant impact on the functionality of the disease and can render a two-lesion configuration more severe compared to a three-lesion configuration. As a result of the complexity of this phenomenon, it was also suggested that certain lesion configurations could result in false negatives in diagnosis when employing a pullback pressure recording across the tandem lesions. In conclusion, this study showed that coronary bifurcation lesions are subject to intricate haemodynamic interactions which render the characterization of their functionality complex and could have significant clinical implications with regards to their diagnosis and prognosis. PMID- 26271707 TI - Bisphenol A and its analogs exhibit different apoptotic potential in peripheral blood mononuclear cells (in vitro study). AB - There are only a few studies that have assessed the effect of bisphenol A (BPA) on human blood cells and no study has been conducted to analyze the impact of BPA analogs on human leucocytes. In this study, we have investigated the effect of BPA and its analogs like bisphenol F (BPF), bisphenol S (BPS) and bisphenol AF (BPAF) on apoptosis induction in human peripheral blood mononuclear cells (PBMCs). In order to clarify the mechanism of bisphenols-induced programmed cell death, changes in various signaling molecules of this process have been assessed. We observed an increase in cytosolic calcium ions (Ca(2+)) level and reduction of transmembrane mitochondrial potential (DeltaPsim) in PBMCs incubated with all compounds examined, and particularly BPA and BPAF. All compounds studied changed PBMCs membrane permeability, activated caspase-8, -9, -3 and induced PARP-1 cleavage and chromatin condensation, which confirmed that they were capable of inducing apoptosis both via intrinsic and extrinsic pathway. Moreover, we have found that modus operandi of bisphenols studied was different. We noticed that BPAF and BPS caused mainly necrotic and apoptotic changes, respectively, whereas BPA induced comparable apoptotic and necrotic effects in the incubated cells. PMID- 26271710 TI - Barriers and facilitators for male carers in accessing formal and informal support: A systematic review. AB - Unpaid, informal carers play a vital role in supporting people with long-term conditions. Being a carer can be challenging and carers may need support but they frequently fail to access it. Compared to research investigating the experiences of female carers, research with male carers is underdeveloped. The available evidence suggests male and female carers have many experiences in common but some research suggests that compared to females, male carers are even less likely to access services. The aim of this systematic review was therefore to synthesise research investigating adult male carers' experiences of accessing formal and informal support focussing on the barriers and facilitators. Nine health and social care electronic databases were searched (e.g. PubMed, PsychINFO, CINAHL Plus, Social Policy and Practice, Scopus). Seven studies (five qualitative and two quantitative) fitting the inclusion criteria were identified. All came from North America and most focussed on older carers caring for people with dementia. All seven studies described barriers to accessing support and three highlighted facilitators. Male carers felt committed to their role, seeing it as their responsibility but were often ambivalent about seeking help. Insufficient service information was frequently emphasised. Participants highlighted positive past experiences and professional or voluntary sector support in providing information and helping access services. Research into male carers' experiences in accessing support remains underdeveloped. Research that distinguishes between, for example, the experiences of spouses and sons and with direct comparisons between male and female carers is needed. Whether gender specific services would benefit male carers remains undetermined. PMID- 26271711 TI - Phosphorylation sites in the Hook domain of CaVbeta subunits differentially modulate CaV1.2 channel function. AB - Regulation of L-type calcium current is critical for the development, function, and regulation of many cell types. Ca(V)1.2 channels that conduct L-type calcium currents are regulated by many protein kinases, but the sites of action of these kinases remain unknown in most cases. We combined mass spectrometry (LC-MS/MS) and whole-cell patch clamp techniques in order to identify sites of phosphorylation of Ca(V)beta subunits in vivo and test the impact of mutations of those sites on Ca(V)1.2 channel function in vitro. Using the Ca(V)1.1 channel purified from rabbit skeletal muscle as a substrate for phosphoproteomic analysis, we found that Ser(193) and Thr(205) in the HOOK domain of Ca(V)beta1a subunits were both phosphorylated in vivo. Ser(193) is located in a potential consensus sequence for casein kinase II, but it was not phosphorylated in vitro by that kinase. In contrast, Thr(205) is located in a consensus sequence for cAMP dependent phosphorylation, and it was robustly phosphorylated in vitro by PKA. These two sites are conserved in multiple Ca(V)beta subunit isoforms, including the principal Ca(V)beta subunit of cardiac Ca(V)1.2 channels, Ca(V)beta2b. In order to assess potential modulatory effects of phosphorylation at these sites separately from the effects of phosphorylation of the alpha11.2 subunit, we inserted phosphomimetic or phosphoinhibitory mutations in Ca(V)beta2b and analyzed their effects on Ca(V)1.2 channel function in transfected nonmuscle cells. The phosphomimetic mutation Ca(V)beta2b(S152E) decreased peak channel currents and shifted the voltage dependence of both activation and inactivation to more positive membrane potentials. The phosphoinhibitory mutation Ca(V)beta2b(S152A) had opposite effects. There were no differences in peak Ca(V)1.2 currents or voltage dependence between the phosphomimetic mutation Ca(V)beta2b(T164D) and the phosphoinhibitory mutation Ca(V)beta2b(T164A). However, calcium-dependent inactivation was significantly increased for the phosphomimetic mutation Ca(V)beta2b(T164D). This effect was subunit-specific, as the corresponding mutation in the palmitoylated isoform, Ca(V)beta2a, had no effect. Overall, our data identify two conserved sites of phosphorylation of the Hook domain of Ca(V)beta subunits in vivo and reveal differential modulatory effects of phosphomimetic mutations in these sites. These results reveal a new dimension of regulation of Ca(V)1.2 channels through phosphorylation of the Hook domains of their beta subunits. PMID- 26271712 TI - Estradiol mediates vasculoprotection via ERRalpha-dependent regulation of lipid and ROS metabolism in the endothelium. AB - The estrogen-mediated vasculoprotective effect has been widely reported in many animal studies, although the clinical trials are controversial and the detailed mechanisms remain unclear. In this study, we focused on the molecular mechanism and consequence of 17beta-estradiol (E2)-induced ERRalpha (estrogen-related receptor alpha) expression in endothelium and its potential beneficial effects on vascular function. The human aorta endothelial cells were used to identify the detailed molecular mechanism and consequences for E2-induced ERRalpha expression through estrogen receptors (ER), where ERalpha responses E2-induced ERRalpha activation, and ERbeta responses basal ERRalpha expression. E2-induced ERRalpha expression increases fatty acid uptake/oxidation with increased mitochondrial replication, ATP generation and attenuated reactive oxygen species (ROS) formation. We have obtained further in vivo proof from high-fat diet mice that the lentivirus-carried endothelium-specific delivery of ERRalpha expression on the vascular wall normalizes E2 deficiency-induced increased plasma lipids with ameliorated vascular damage. ERRalpha knockdown worsens the problem, and the E2 could only partly restore this effect. This is the first time we report the detailed mechanism with direct evidence that E2-induced ERRalpha expression modulates the fatty acid metabolism and reduces the circulating lipids through endothelium. We conclude that E2-induced ERRalpha expression in endothelium plays an important role for the E2-induced vasculoprotective effect. PMID- 26271714 TI - On the long-term outcome of orthostatic tremor. PMID- 26271713 TI - The changing role of ER in endocrine resistance. AB - Estrogen receptor (ER) is expressed in approximately 70% of newly diagnosed breast tumors. Although endocrine therapy targeting ER is highly effective, intrinsic or acquired resistance is common, significantly jeopardizing treatment outcomes and minimizing overall survival. Even in the presence of endocrine resistance, a continued role of ER signaling is suggested by several lines of clinical and preclinical evidence. Indeed, inhibition or down-regulation of ER reduces tumor growth in preclinical models of acquired endocrine resistance, and many patients with recurrent ER+ breast tumors progressing on one type of ER targeted treatment still benefit from sequential endocrine treatments that target ER by a different mechanism. New insights into the nature and biology of ER have revealed several mechanisms sustaining altered ER signaling in endocrine resistant tumors, including deregulated growth factor receptor signaling that results in ligand-independent ER activation, unbalanced ER co-regulator activity, and genomic alterations involving the ER gene ESR1. Therefore, biopsies of recurrent lesions are needed to assess the changes in epi/genomics and signaling landscape of ER and associated pathways in order to tailor therapies to effectively overcome endocrine resistance. In addition, more completely abolishing the levels and activity of ER and its co-activators, in combination with selected signal transduction inhibitors or agents blocking the upstream or downstream targets of the ER pathway, may provide a better therapeutic strategy in combating endocrine resistance. PMID- 26271715 TI - The H2S-producing enzyme CSE is dispensable for the processing of inflammatory and neuropathic pain. AB - Accumulating lines of evidence indicate that hydrogen sulfide (H2S) contributes to the processing of chronic pain. However, the sources of H2S production in the nociceptive system are poorly understood. Here we investigated the expression of the H2S releasing enzyme cystathionine gamma-lyase (CSE) in the nociceptive system and characterized its role in chronic pain signaling using CSE deficient mice. We show that paw inflammation and peripheral nerve injury led to upregulation of CSE expression in dorsal root ganglia. However, conditional knockout mice lacking CSE in sensory neurons as well as global CSE knockout mice demonstrated normal pain behaviors in inflammatory and neuropathic pain models as compared to WT littermates. Thus, our results suggest that CSE is not critically involved in chronic pain signaling in mice and that sources different from CSE mediate the pain relevant effects of H2S. PMID- 26271716 TI - Hippocampal NMDA receptors are involved in rats' spontaneous object recognition only under high memory load condition. AB - The possible involvement of hippocampal N-methyl-D-aspartate (NMDA) receptors in spontaneous object recognition was investigated in rats under different memory load conditions. We first estimated rats' object memory span using 3-5 objects in "Different Objects Task (DOT)" in order to confirm the highest memory load condition in object recognition memory. Rats were allowed to explore a field in which 3 (3-DOT), 4 (4-DOT), or 5 (5-DOT) different objects were presented. After a delay period, they were placed again in the same field in which one of the sample objects was replaced by another object, and their object exploration behavior was analyzed. Rats could differentiate the novel object from the familiar ones in 3-DOT and 4-DOT but not in 5-DOT, suggesting that rats' object memory span was about 4. Then, we examined the effects of hippocampal AP5 infusion on performance in both 2-DOT (2 different objects were used) and 4-DOT. The drug treatment before the sample phase impaired performance only in 4-DOT. These results suggest that hippocampal NMDA receptors play a critical role in spontaneous object recognition only when the memory load is high. PMID- 26271718 TI - Clinical and microbiologic characteristics of adult patients with recurrent bacteraemia caused by extended-spectrum beta-lactamase-producing Escherichia coli or Klebsiella pneumoniae. AB - The characteristics of patients with recurrent bacteraemia caused by extended spectrum beta-lactamase (ESBL)-producing Escherichia coli or Klebsiella pneumoniae (EK) are rarely described. Flomoxef belongs to the cephamycins group and demonstrates in vitro activity against ESBL-producing organisms. Whether flomoxef may be used for the treatment of such infections remains controversial. This retrospective case-control study enrolled adult patients who had bacteraemia caused by ESBL-EK during 2005-2011. Case patients were those who had more than one episode of ESBL-EK bacteraemia. Controls were those who were matched for age and interval time of blood sampling and had only one episode of ESBL-EK bacteraemia with subsequent bacteraemia episodes caused by other non-ESBL-EK bacteria. Pulsed-field gel electrophoresis and microbiologic profiles of the initial and subsequent ESBL-EK isolates were analysed. During the study period, 424 patients were found to have at least one positive blood culture after the first ESBL-EK bacteraemia episode, and 67 (15.8%) had a second episode of ESBL-EK bacteraemia. Bacteraemia resulting from vascular catheter-related infection (odds ratio, 3.24; 95% confidence interval, 1.31-8.05), and definitive therapy with flomoxef (odds ratio, 2.99; 95% confidence interval, 1.10-8.15) were both independent risk factors for the recurrence. Among the 56 patients with available ESBL-EK isolates for analysis, 38 (67.8%) were infected by genetically similar strains. In three of these 38 recurrent ESBL-EK bacteraemia cases caused by an identical strain, the minimum inhibitory concentrations of carbapenem for the subsequent K. pneumoniae isolates were fourfold or higher than the initial isolates. Recurrent bacteraemia was not uncommon in our patients with ESBL-EK bacteraemia, and most of the episodes were caused by identical strains. PMID- 26271719 TI - The neural basis of hand gesture comprehension: A meta-analysis of functional magnetic resonance imaging studies. AB - Gestures play an important role in face-to-face communication and have been increasingly studied via functional magnetic resonance imaging. Although a large amount of data has been provided to describe the neural substrates of gesture comprehension, these findings have never been quantitatively summarized and the conclusion is still unclear. This activation likelihood estimation meta-analysis investigated the brain networks underpinning gesture comprehension while considering the impact of gesture type (co-speech gestures vs. speech-independent gestures) and task demand (implicit vs. explicit) on the brain activation of gesture comprehension. The meta-analysis of 31 papers showed that as hand actions, gestures involve a perceptual-motor network important for action recognition. As meaningful symbols, gestures involve a semantic network for conceptual processing. Finally, during face-to-face interactions, gestures involve a network for social emotive processes. Our finding also indicated that gesture type and task demand influence the involvement of the brain networks during gesture comprehension. The results highlight the complexity of gesture comprehension, and suggest that future research is necessary to clarify the dynamic interactions among these networks. PMID- 26271717 TI - S-nitrosoglutathione reduces tau hyper-phosphorylation and provides neuroprotection in rat model of chronic cerebral hypoperfusion. AB - We have previously reported that treatment of rats subjected to permanent bilateral common carotid artery occlusion (pBCCAO), a model of chronic cerebral hypoperfusion (CCH), with S-nitrosoglutathione (GSNO), an endogenous nitric oxide carrier, improved cognitive functions and decreased amyloid-beta accumulation in the brains. Since CCH has been implicated in tau hyperphosphorylation induced neurodegeneration, we investigated the role of GSNO in regulation of tau hyperphosphorylation in rat pBCCAO model. The rats subjected to pBCCAO had a significant increase in tau hyperphosphorylation with increased neuronal loss in hippocampal/cortical areas. GSNO treatment attenuated not only the tau hyperphosphorylation, but also the neurodegeneration in pBCCAO rat brains. The pBCCAO rat brains also showed increased activities of GSK-3beta and Cdk5 (major tau kinases) and GSNO treatment significantly attenuated their activities. GSNO attenuated the increased calpain activities and calpain-mediated cleavage of p35 leading to production of p25 and aberrant Cdk5 activation. In in vitro studies using purified calpain protein, GSNO treatment inhibited calpain activities while 3-morpholinosydnonimine (a donor of peroxynitrite) treatment increased its activities, suggesting the opposing role of GSNO vs. peroxynitrite in regulation of calpain activities. In pBCCAO rat brains, GSNO treatment attenuated the expression of inducible nitric oxide synthase (iNOS) expression and also reduced the brain levels of nitro-tyrosine formation, thereby indicating the protective role of GSNO in iNOS/nitrosative-stress mediated calpain/tau pathologies under CCH conditions. Taken together with our previous report, these data support the therapeutic potential of GSNO, a biological NO carrier, as a neuro- and cognitive protective agent under conditions of CCH. PMID- 26271721 TI - The role of branched chain amino acid and tryptophan metabolism in rat's behavioral diversity: Intertwined peripheral and brain effects. AB - Previously, we showed that a transient early-in-life interference with the expression of multiple genes by mithramycin (MTR) followed by later-in-life exposure to chronic stress, leads to a "daring" and novelty seeking behavior in rats. In this study we searched for molecular changes that contribute to this behavioral alteration. We applied a non-hypothesis driven strategy using whole genome cDNA array analysis (WGA) followed by Genome Scale Metabolic modeling analysis (GSMM). Gene expression validation was performed by qRT-PCR and immunoblotting. Brain and serum amino acids levels were measured by HPLC. WGA data directed us towards metabolic pathways and GSMM pointed at branched chain amino acids (BCAA) pathway. Out of 21 amino acids analyzed in the prefrontal cortex of MTR+Stress rats only tryptophan, whose brain levels depend on serum BCAA levels, showed a significant decrease. No change was observed in serotonin or kynurenine levels. However, a significant reduction in mRNA and protein levels of the large neutral amino acid transporter (LAT1), which transports BCAA and tryptophan into the brain, as well as in serum levels of tryptophan/BCAA ratio were observed. The latter may be attributed to the failure to increase serum insulin, following stress, in rats pre-exposed to mithramycin. Finally, significant correlations were observed between the anxiety index and tryptophan and between T-maze errors and LAT1. This study shows a specific behavioral pattern, which is linked to modulations in fluxes of amino acids both peripheral and central, which converge and reciprocally interact, and may thus be equally important targets for therapeutic intervention. PMID- 26271722 TI - Sonic hedgehog signaling regulates amygdalar neurogenesis and extinction of fear memory. AB - It is now recognized that neurogenesis occurs throughout life predominantly in the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ) of the lateral ventricle. In the present study, we investigated the relationship between neurogenesis in the amygdala and extinction of fear memory. Mice received 15 tone-footshock pairings. Twenty-four hours after training, the mice were given 15 tone-alone trials (extinction training) once per day for 7 days. Two hours before extinction training, the mice were injected intraperitoneally with 5-bromo 3-deoxyuridine (BrdU). BrdU-positive and NeuN-positive cells were analyzed 52 days after the training. A group of mice that received tone-footshock pairings but no extinction training served as controls (FC+No-Ext). The number of BrdU(+)/NeuN(+) cells was significantly higher in the extinction (FC+Ext) than in the FC+No-Ext mice. Proliferation inhibitor methylazoxymethanol acetate (MAM) or DNA synthesis inhibitor cytosine arabinoside (Ara-C) reduced neurogenesis and retarded extinction. Silencing Sonic hedgehog (Shh) gene with short hairpin interfering RNA (shRNA) by means of a retrovirus expression system to knockdown Shh specifically in the mitotic neurons reduced neurogenesis and retarded extinction. By contrast, over-expression of Shh increased neurogenesis and facilitated extinction. These results suggest that amygdala neurogenesis and Shh signaling are involved in the extinction of fear memory. PMID- 26271723 TI - Novel microscopy-based screening method reveals regulators of contact-dependent intercellular transfer. AB - Contact-dependent intercellular transfer (codeIT) of cellular constituents can have functional consequences for recipient cells, such as enhanced survival and drug resistance. Pathogenic viruses, prions and bacteria can also utilize this mechanism to spread to adjacent cells and potentially evade immune detection. However, little is known about the molecular mechanism underlying this intercellular transfer process. Here, we present a novel microscopy-based screening method to identify regulators and cargo of codeIT. Single donor cells, carrying fluorescently labelled endocytic organelles or proteins, are co-cultured with excess acceptor cells. CodeIT is quantified by confocal microscopy and image analysis in 3D, preserving spatial information. An siRNA-based screening using this method revealed the involvement of several myosins and small GTPases as codeIT regulators. Our data indicates that cellular protrusions and tubular recycling endosomes are important for codeIT. We automated image acquisition and analysis to facilitate large-scale chemical and genetic screening efforts to identify key regulators of codeIT. PMID- 26271720 TI - Evidence for the role of corticotropin-releasing factor in major depressive disorder. AB - Major depressive disorder (MDD) is a devastating disease affecting over 300 million people worldwide, and costing an estimated 380 billion Euros in lost productivity and health care in the European Union alone. Although a wealth of research has been directed toward understanding and treating MDD, still no therapy has proved to be consistently and reliably effective in interrupting the symptoms of this disease. Recent clinical and preclinical studies, using genetic screening and transgenic rodents, respectively, suggest a major role of the CRF1 gene, and the central expression of CRF1 receptor protein in determining an individual's risk of developing MDD. This gene is widely expressed in brain tissue, and regulates an organism's immediate and long-term responses to social and environmental stressors, which are primary contributors to MDD. This review presents the current state of knowledge on CRF physiology, and how it may influence the occurrence of symptoms associated with MDD. Additionally, this review presents findings from multiple laboratories that were presented as part of a symposium on this topic at the annual 2014 meeting of the International Behavioral Neuroscience Society (IBNS). The ideas and data presented in this review demonstrate the great progress that has been made over the past few decades in our understanding of MDD, and provide a pathway forward toward developing novel treatments and detection methods for this disorder. PMID- 26271725 TI - Recombinant interferon-alpha in myelofibrosis reduces bone marrow fibrosis, improves its morphology and is associated with clinical response. AB - Recombinant interferon-alpha represents a well-established therapeutic option for the treatment of polycythemia vera and essential thrombocythemia. Recent studies also suggest a role for recombinant interferon-alpha in the treatment of 'early stage' primary myelofibrosis, but few studies have reported the bone marrow changes after clinically successful interferon therapy. The aim of the present study is to detail the histological responses to recombinant interferon-alpha in primary myelofibrosis and post-polycythemia vera/post-essential thrombocythemia myelofibrosis and to correlate these with clinical findings. We retrospectively studied 12 patients with primary myelofibrosis or post-polycythemia vera/post essential thrombocythemia myelofibrosis, who had been treated with recombinant interferon-alpha. Six patients had received other prior cytoreductive therapies. Bone marrow biopsy was assessed for the following histological parameters: (i) cellularity; (ii) myeloid-to-erythroid ratio; (iii) megakaryocyte tight clusters; (iv) megakaryocyte and naked nuclei density; (v) megakaryocytic atypia; (vi) fibrosis; and (vii) the percentage of blasts. Clinical and laboratory data were included: (i) constitutional symptoms; (ii) splenomegaly, if present; and (iii) complete cell blood count. The clinical response to therapy was evaluated using the International Working Group for Myelofibrosis Research and Treatment/European LeukemiaNet response criteria. The Dynamic International Prognostic Scoring System (DIPSS) score was calculated before and after recombinant interferon-alpha administration. Successful interferon therapy for myelofibrosis was associated with a significant reduction of marrow fibrosis, cellularity, megakaryocyte density and naked nuclei density. The presence of JAK2(V617F) mutation correlated with improved DIPSS score. JAK2(V617F)-negative cases showed worsening of such score or evolution to acute myeloid leukemia. Cytogenetic analysis documented a normal karyotype in all cases. In conclusion, successful clinical response to interferon-alpha correlates well with an improvement of bone marrow morphology. The prognostic effect of such therapy may be influenced by the JAK2 mutational status. Additional studies are needed to confirm these preliminary data. PMID- 26271726 TI - Fulminant Central Plus Peripheral Nervous System Demyelination without Antibodies to Neurofascin. AB - BACKGROUND: Combined central and peripheral nervous system demyelination is a rare and poorly described phenomenon. Recently, anti-neurofascin antibodies were reported to be positive in 86% of these patients in a Japanese cohort. Yet, there seems to be a clinical, radiological, and serological heterogeneity among these patients. In this report, our aim is to describe characteristics of our patients with this entity and compare with others in the literature. METHODS: We report clinical, electrophysiological, radiological, and laboratory characteristics of five patients with both multiple sclerosis and chronic inflammatory demyelinating polyradiculoneuropathy from our institutional database containing 1890 MS patients. RESULTS: Three patients presented with extensive, active demyelination of both central nervous system and peripheral nervous system with hypertrophic peripheral nerves. Plexuses, trunks, division and cords were involved in the process. Oligoclonal band was negative. Conduction block was not detected. Corticosteroid treatment was not adequate. Others had a slowly progressive clinical course. Serum anti-neurofascin antibody was negative. Review of the literature revealed similar cases with active disease, early-onset hypertrophic peripheral nerves, and central demyelination, in addition to other cases with an insidious course. CONCLUSIONS: Patients with combined central and peripheral demyelination form a spectrum. Some patients may have an antibody-mediated syndrome with or without anti-neurofascin antibodies and others seem to represent a coincidence. PMID- 26271724 TI - BRAF V600E and risk stratification of thyroid microcarcinoma: a multicenter pathological and clinical study. AB - Studies from single institutions have analyzed BRAF in papillary microcarcinomas, sometimes with contradictory results. Most of them have provided limited integration of histological and clinical data. To obtain a comprehensive picture of BRAF V600E-mutated microcarcinomas and to evaluate the role of BRAF testing in risk stratification we performed a retrospective multicenter analysis integrating microscopical, pathological, and clinical information. Three hundred and sixty five samples from 300 patients treated at six medical institutions covering different geographical regions of Italy were analyzed with central review of all cases. BRAF V600E statistical analysis was conducted on 298 microcarcinomas from 264 patients after exclusion of those that did not meet the required criteria. BRAF V600E was identified in 145/298 tumors (49%) including the following subtypes: 35/37 (95%, P<0.0001) tall cell and 72/114 (64%, P<0.0001) classic; conversely 94/129 follicular variant papillary microcarcinomas (73%, P<0.0001) were BRAF wild type. BRAF V600E-mutated microcarcinomas were characterized by markedly infiltrative contours (P<0.0001) with elongated strings of neoplastic cells departing from the tumor, and by intraglandular tumor spread (P<0.0001), typically within 5 mm of the tumor border. Multivariate analysis correlated BRAF V600E with specific microscopic features (nuclear grooves, optically clear nuclei, tall cells within the tumor, and tumor fibrosis), aggressive growth pattern (infiltrative tumor border, extension into extrathyroidal tissues, and intraglandular tumor spread), higher American Thyroid Association recurrence risk group, and non-incidental tumor discovery. The following showed the strongest link to BRAF V600E: tall cell subtype, many neoplastic cells with nuclear grooves or with optically clear nuclei, infiltrative growth, intraglandular tumor spread, and a tumor discovery that was non-incidental. BRAF V600E-mutated microcarcinomas represent a distinct biological subtype. The mutation is associated with conventional clinico-pathological features considered to be adverse prognostic factors for papillary microcarcinoma, for which it could be regarded as a surrogate marker. BRAF analysis may be useful to identify tumors (BRAF wild type) that have negligible clinical risk. PMID- 26271727 TI - High-yield isolation of extracellular vesicles using aqueous two-phase system. AB - Extracellular vesicles (EVs) such as exosomes and microvesicles released from cells are potential biomarkers for blood-based diagnostic applications. To exploit EVs as diagnostic biomarkers, an effective pre-analytical process is necessary. However, recent studies performed with blood-borne EVs have been hindered by the lack of effective purification strategies. In this study, an efficient EV isolation method was developed by using polyethylene glycol/dextran aqueous two phase system (ATPS). This method provides high EV recovery efficiency (~70%) in a short time (~15 min). Consequently, it can significantly increase the diagnostic applicability of EVs. PMID- 26271729 TI - UPRT, a suicide-gene therapy candidate in higher eukaryotes, is required for Drosophila larval growth and normal adult lifespan. AB - Uracil phosphoribosyltransferase (UPRT) is a pyrimidine salvage pathway enzyme that catalyzes the conversion of uracil to uridine monophosphate (UMP). The enzyme is highly conserved from prokaryotes to humans and yet phylogenetic evidence suggests that UPRT homologues from higher-eukaryotes, including Drosophila, are incapable of binding uracil. Purified human UPRT also do not show any enzymatic activity in vitro, making microbial UPRT an attractive candidate for anti-microbial drug development, suicide-gene therapy, and cell-specific mRNA labeling techniques. Nevertheless, the enzymatic site of UPRT remains conserved across the animal kingdom indicating an in vivo role for the enzyme. We find that the Drosophila UPRT homologue, krishah (kri), codes for an enzyme that is required for larval growth, pre-pupal/pupal viability and long-term adult lifespan. Our findings suggest that UPRT from all higher eukaryotes is likely enzymatically active in vivo and challenges the previous notion that the enzyme is non-essential in higher eukaryotes and cautions against targeting the enzyme for therapeutic purposes. Our findings also suggest that expression of the endogenous UPRT gene will likely cause background incorporation when using microbial UPRT as a cell-specific mRNA labeling reagent in higher eukaryotes. PMID- 26271730 TI - Enhancing the hydrogen bond between the bridged hydrogen atom of diborane and ammonia. AB - The character of the bridged hydrogen atom (Hb) of B2H6 has become a hot issue in recent years. In this work, the complexes B2H6 . . . NH3, B2H2X4 . . . nNH3 (n = 1, 2) and 2HF . . . B2H2X4 . . . 2NH3 (X = Cl, Br, I) were constructed and studied based on the M06-2X calculations to investigate how to enhance the Hb . . . N hydrogen-bonded interaction. When the terminal hydrogen atoms (Ht) of B2H6 were replaced by X (X = Cl, Br, I) atoms, the Hb . . . N hydrogen bond were strengthened. According to the electrostatic potentials in B2H2X4, two HF molecules were added to the interspace of the B-H-B-H four-membered ring of the B2H2X4 . . . 2NH3 complexes, and H . . . X hydrogen bond formed, resulting in further enhancing effect of Hb . . . N hydrogen bond. As a result, the positive cooperative effect of Hb . . . N hydrogen bond and H . . . X hydrogen bond do enhance the interactions of each other. The two measures not only enhance the strength of Hb . . . N hydrogen bond, but also achieve the goal to make the Hb . . . N hydrogen bond perpendicular to B . . . B direction. PMID- 26271728 TI - Bax monomers form dimer units in the membrane that further self-assemble into multiple oligomeric species. AB - Bax is a key regulator of apoptosis that mediates the release of cytochrome c to the cytosol via oligomerization in the outer mitochondrial membrane before pore formation. However, the molecular mechanism of Bax assembly and regulation by other Bcl-2 members remains obscure. Here, by analysing the stoichiometry of Bax oligomers at the single-molecule level, we find that Bax binds to the membrane in a monomeric state and then self-assembles in <1 min. Strikingly, active Bax does not exist in a unique oligomeric state, but as several different species based on dimer units. Moreover, we show that cBid activates Bax without affecting its assembly, while Bcl-xL induces the dissociation of Bax oligomers. On the basis of our experimental data and theoretical modelling, we propose a new mechanism for the molecular pathway of Bax assembly to form the apoptotic pore. PMID- 26271731 TI - Structures and formation mechanisms of aquo/hydroxo oligomeric beryllium in aqueous solution: a density functional theory study. AB - The structures and formation mechanisms of a wide variety of aquo/hydroxo oligomeric beryllium clusters were investigated using density functional theory. The structural parameters of beryllium clusters were found to vary regularly with the stepwise substitution of bound water molecules in the inner coordination sphere by hydroxyl groups. According to the Gibbs free energies deduced from SMD solvation model computations, unhydrolyzed oligomeric beryllium species are the most favorable products of polymerization, independent of the degrees of hydrolysis of the reactants. Simulation of the formation processes of oligomeric beryllium showed that polymerization, in essence, involves the nucleophilic attack of a terminal hydroxyl group in one BeO4 tetrahedron on the beryllium center in another BeO4 tetrahedron, leading to the bridging of two BeO4 tetrahedrons by a hydroxyl group. PMID- 26271732 TI - An insight into hydration structure of sodium glycinate from ab initio quantum chemical study. AB - The hydration structure of sodium glycinate (Na(+)GL(-)) is probed by the Monte Carlo multiple minimum (MCMM) method combined with quantum mechanical (QM) calculations at the MP2/6-311++G(d,p) level. In the gas phase, the energy of [Na(+)GL(-)]beta is more than 30 kJ mol(-1) higher than [Na(+)GL(-)]alpha. With higher degrees of hydration, our results indicate that the most stable conformers of [Na(+)GL(-)]?(H2O)8 were derived from [Na(+)GL(-)]beta instead of [Na(+)GL( )]alpha. The stable conformers determined by the conductor-like polarizable continuum model (CPCM) also show that [Na(+)GL(-)]beta is more stable than [Na(+)GL(-)]alpha in the liquid phase. By analyzing the hydration process, water...water hydrogen bonding interaction will be more preferable than ion...water interaction as the number of water molecules increases. According to the electronic density at the bond critical point on the Na-X bonds (X = O1, O2, N) in the low-energy conformers, Na(+)GL(-) will be dissociated as Na(+) and GL( ) in the bulk water, which is not predicted by the CPCM model. The structure features and the charge redistribution of Na(+)GL(-) will provide a physical explanation for the weakening Na-O1 interaction. PMID- 26271733 TI - Molecular dynamic simulations of the water absorbency of hydrogels. AB - A polymer gel can imbibe solvent molecules through surface tension effect. When the solvent happens to be water, the gel can swell to a large extent and forms an aggregate called hydrogel. The large deformation caused by such swelling makes it difficult to study the behaviors of hydrogels. Currently, few molecular dynamic simulation works have been reported on the water absorbing mechanism of hydrogels. In this paper, we first use molecular dynamic simulation to study the water absorbing mechanism of hydrogels and propose a hydrogel-water interface model to study the water absorbency of the hydrogel surface. Also, the saturated water content and volume expansion rate of the hydrogel are investigated by building a hydrogel model with different cross-linking degree and by comparing the water absorption curves under different temperatures. The sample hydrogel model used consists of Polyethylene glycol diglycidyl ether (PEGDGE) as epoxy and the Jeffamine, poly-oxy-alkylene-amines, as curing agent. The conclusions obtained are useful for further investigation on PEGDGE/Jeffamine hydrogel. Moreover, the simulation methods, including hydrogel-water interface modeling, we first propose are also suitable to study the water absorbing mechanism of other hydrogels. PMID- 26271734 TI - Highly conductive and stable polysiloxane-modified perylenebisimide nanosheets and nanowires by self-assembly and subsequent condensation. AB - Perylenebisimide (PBI) nanowires and nanosheets with high chemical and mechanical stability are prepared by a simple way. Firstly, a PBI-based organosilane precursor PBI-Si(OEt)3 was synthesized. Its nanostructures were then assembled by a solvent-exchange method. The nanostructures could be adjusted by assembling in different solvents. The obtained nanostructures were finally fixed by acetic acid vapor treatment through polycondensation of the triethoxysilyl groups in the precursors. After polycondensation, the nanostructures hardly change and they become insoluble in common solvents. Moreover, the conductivity of the polycondensed nanowires and nanosheets are ca. 35-40 times than that of polycondensed spin-coated PBI-Si(OEt)3 film by current sensing atomic force microscopy (CSAFM). PMID- 26271735 TI - Chloroquine inhibits the malignant phenotype of glioblastoma partially by suppressing TGF-beta. AB - BACKGROUND: Glioblastoma (GBM), the most common and aggressive primary brain tumor, is characterized by excessive brain infiltration which prevents the complete surgical resection. These tumors also display treatment non-compliance and responses to standard therapy are invariably transient; consequently, the prognosis barely exceeds 14 months and recurrence is inevitable. Accordingly, several new treatment strategies have been studied. One such option is the use of chloroquine (CQ), a lysosomotropic weak base and renowned antimalarial drug, that has shown promising results in several pre-clinical studies. In this paper, we investigate the efficiency of CQ to hinder the malignant phenotype of GBM, namely extensive proliferation, invasion and radio-resistance. RESULTS: In cell cycle analysis, proliferation assays and immunofluorescence, CQ treatments halved proliferation of primary cultures from GBM specimens and GBM cell lines (U-373 MG et U-87 MG). Gelatin zymography and Matrigel(TM)-coated transwell invasion assays also revealed a 50 % CQ induced inhibition of MMP-2 activity and GBM invasion. Concomitant treatment with CQ and radiation also radiosensitized GBM cells as shown by an accumulation in the G2/M phase, increased cell death and reduced clonogenic formation. Moreover, radiation-induced invasion was considerably restrained by CQ. We also observe that these effects are owed to CQ-induced inhibition of TGF-beta secretion and signaling pathway, a predominant growth factor in GBM progression. CONCLUSION: These results suggest that CQ, alone or as an adjuvant therapeutic, could be used to inhibit the GBM malignant phenotype and could benefit GBM afflicted patients. PMID- 26271737 TI - [Long-term results of autologous transplantation of limbal epithelium cultivated ex vivo for limbal stem cell deficiency]. AB - OBJECTIVE: This study reports the long-term clinical outcome of autologous limbal epithelial cells cultivated ex vivo on intact amniotic membranes (AM) for ocular surface reconstruction in limbal stem cell deficiency (LSCD). PATIENTS AND METHODS: A total of 61 eyes from 57 patients (46 males and 11 females) with LSCD were treated by transplantation of autologous limbal epithelial cells cultivated on intact AM. The etiology of the LSCD was chemical and thermal burns (n = 34), recurrent or primary large-sized pterygium (n = 12), mitomycin C and tumor excision-induced LSCD (n = 9), severe infectious keratitis (n = 3), perforating injury, epidermolysis bullosa and contact lens-associated keratopathy (each n = 1). Only eyes with a follow-up time of at least 12 months were included in the analysis. The main outcome end points were restoration of ocular surface integrity and improvement of visual acuity (VA). RESULTS: The mean follow-up time was 50.8 +/- 32.7 months. An entirely stable corneal surface was reconstructed in 46 (75.4%) eyes. Visual acuity significantly increased in 40 (65.6 %) eyes, was stable in 12 (19.7%) eyes and decreased in 9 eyes (14.8%). The mean visual acuity significantly increased (p < 0.0001) from 1.4 +/- 0.91 LogMAR preoperatively to 0.8+/- 0.67 LogMAR postoperatively. CONCLUSION: Transplantation of limbal epithelium cultivated ex vivo on intact AM leads to restoration of a stable corneal surface and resulted in a significant increase of visual acuity in most cases of LSCD. Autologous transplantation of cultivated limbal epithelium showed an excellent prognosis and outcome after long-term follow-up. PMID- 26271736 TI - Efficacy of artemether-lumefantrine therapy for the treatment of uncomplicated Plasmodium falciparum malaria in Southwestern Ethiopia. AB - BACKGROUND: The development and spread of chloroquine-resistant Plasmodium falciparum threatens the health of millions of people and poses a major challenge to the control of malaria. Monitoring drug efficacy in 2-year intervals is an important tool for establishing rational anti-malarial drug policies. This study addresses the therapeutic efficacy of artemether-lumefantrine (AL) for the treatment of Plasmodium falciparum in southwestern Ethiopia. METHODS: A 28-day in vivo therapeutic efficacy study was conducted from September to December, 2011, in southwestern Ethiopia. Participants were selected for the study if they were older than 6 months, weighed more than 5 kg, symptomatic, and had microscopically confirmed, uncomplicated P. falciparum. All 93 eligible patients were treated with AL and followed for 28 days. For each patient, recurrence of parasitaemia, the clinical condition, and the presence of gametoytes were assessed on each visit during the follow-up period. PCR was conducted to differentiate re infection from recrudescence. RESULTS: Seventy-four (83.1 %) of the study subjects cleared fever by day 1, but five (5.6 %) had fever at day 2. All study subjects cleared fever by day 3. Seventy-nine (88.8 %) of the study subjects cleared the parasite by day 1, seven (7.9 %) were blood-smear positive by day 1, and three (3.4 %) were positive by day 2. In five patients (5.6 %), parasitaemia reappeared during the 28-day follow-up period. From these five, one (1.1 %) was a late clinical failure, and four (4.5 %) were a late parasitological failure. On the day of recurrent parasitaemia, the level of chloroquine/desethylchloroquine (CQ-DCQ) was above the minimum effective concentration (>100 ng/ml) in one patient. There were 84 (94.4 %) adequate clinical and parasitological responses. The 28-day, PCR-uncorrected (unadjusted by genotyping) cure rate was 84 (94.4 %), whereas the 28-day, PCR-corrected cure rate was 87 (97.8 %). Of the three re infections, two (2.2 %) were due to P. falciparum and one (1.1 %) was due to P. vivax. From 89 study subjects, 12 (13.5 %) carried P. falciparum gametocytes at day 0, whereas the 28-day gametocyte carriage rate was 2 (2.2 %). CONCLUSIONS: Years after the introduction of AL in Ethiopia, the finding of this study is that AL has been highly effective in the treatment of uncomplicated P. falciparum malaria and reducing gametocyte carriage in southwestern Ethiopia. PMID- 26271738 TI - [Recurrent keratoconjunctivitis]. AB - BACKGROUND: Molluscum contagiosum is a highly infectious viral disease of the skin and mucous membranes. These lesions are found particularly often in children and young adults and are generally self-limiting. Nevertheless, molluscum contagiosum lesions in close vicinity to the eyes should be actively removed if they cause conjunctival or corneal irritation. CASE REPORT: We report the case of a 14-year-old boy who was treated for approximately 9 months for recurrent chronic keratoconjunctivitis with corneal neovascularization. Careful inspection of the eyelids revealed molluscum contagiosum. After removal of the lesions on both sides, short-term anti-inflammatory therapy and long-term surface lubrication, a gradual improvement was observed so that an almost complete visual recovery was achieved. CONCLUSION: In long-standing keratoconjunctivitis refractory to treatment, special attention should be paid to the possible presence of molluscum contagiosum, particularly in children and the lesions should be promptly removed. PMID- 26271739 TI - [Stem cell therapy for retinal diseases]. AB - BACKGROUND: Due to an ageing population the incidence and prevalence of retinal diseases and visual disabilities will continue to grow. A great number of patients would principally be able to benefit from a stem cell-based therapy. OBJECTIVES: To introduce readers to the terminology and current concepts associated with stem cell therapy in ocular research and to provide an overview of the current status of preclinical and clinical research. MATERIAL AND METHODS: We performed a systematic review of relevant entries on ocular stem cell therapy for retinal diseases in PubMed and ClinicalTrials.gov. Differences between various stem cell types are displayed systematically, followed by a discussion of preclinical studies. Translational aspects are highlighted leading to the first clinical trials, including surgical and ethical facets. RESULTS: In preclinical studies, photoreceptor cell precursors and retinal pigment epithelium (RPE) cells were differentiated and subretinally transplanted into animal models. Besides exclusion of a teratoma formation, some functional improvements were also observed. Intraocular transplantation of stem cell-derived RPE cells was the first successful clinical application of pluripotent stem cells in man. CONCLUSION: Promising results of preclinical and clinical studies have identified important challenges and confirmed the potential of stem cell therapy for ophthalmology. PMID- 26271740 TI - Microbial Community Composition and Extracellular Enzyme Activities Associated with Juncus roemerianus and Spartina alterniflora Vegetated Sediments in Louisiana Saltmarshes. AB - Saltmarshes are typically dominated by perennial grasses with large underground rhizome systems that can change local sediment conditions and be important in shaping the sediment microbial community. Factors such as salinity that control plant zonation in saltmarshes are also likely to influence the microbial community, but little is known as to whether microbial communities share distribution patterns with plants in these systems. To determine the extent to which microbial assemblages are influenced by saltmarsh plant communities, as well as to examine patterns in microbial community structure at local and regional scales, we sampled sediments at three saltmarshes in Louisiana, USA. All three systems exhibit a patchy distribution of Juncus roemerianus stands within a Spartina alterniflora marsh. Sediment samples were collected from the interior of several J. roemerianus stands as well as from the S. alterniflora matrix. Samples were assayed for extracellular enzyme activity and DNA extracted to determine microbial community composition. Denaturing gradient gel electrophoresis of rRNA gene fragments was used to determine regional patterns in bacterial, archaeal, and fungal assemblages, while Illumina sequencing was used to examine local, vegetation-driven, patterns in community structure at one site. Both enzyme activity and microbial community structure were primarily influenced by regional site. Within individual saltmarshes, bacterial and archaeal communities differed between J. roemerianus and S. alterniflora vegetated sediments, while fungal communities did not. These results highlight the importance of the plant community in shaping the sediment microbial community in saltmarshes but also demonstrate that regional scale factors are at least as important. PMID- 26271742 TI - Tracheostomy procedures in the intensive care unit: an international survey. AB - INTRODUCTION: Percutaneous dilatational tracheostomy (PDT) is one of the most frequent procedures performed in the intensive care unit (ICU). PDT may add potential benefit to clinical management of critically ill patients. Despite this, no clinical guidelines are available. We sought to characterize current practice in this international survey. METHODS: An international survey, endorsed and peer reviewed by European Society of Intensive Care Medicine (ESICM), was carried out from May to October 2013. The questionnaire was accessible from the ESICM website in the 'survey of the month' section. RESULTS: 429 physicians from 59 countries responded to this survey. Single step dilatational tracheostomy was the most used PDT in ICU. Almost 75% of PDT's were performed by intensive care physicians. The main indication for PDT was prolonged mechanical ventilation. Tracheostomies were most frequently performed between 7-15 days after ICU admission. Volume control mechanical ventilation, and a combination of sedation, analgesia, neuromuscular blocking agents and fiberoptic bronchoscopy were used. Surgical tracheostomy was mainly performed in ICU by ENT specialists, and was generally chosen when for patients at increased risk for difficult PDT insertion. Bleeding controlled by compression and stoma infection/inflammation were the most common intra-procedural and late complications, respectively. Informed consent for PDT was obtained in only 60% of cases. CONCLUSIONS: This first international picture of current practices in regard to tracheostomy insertion demonstrates considerable geographic variation in practice, suggesting a need for greater standardization of approaches to tracheostomy insertion. PMID- 26271743 TI - Outcomes of surgical resection and loco-regional therapy in patients with stage 3A hepatocellular carcinoma: a retrospective review from the national cancer database. AB - OBJECTIVES: In advanced stages, hepatocellular carcinoma (HCC) is often associated with major vascular involvement (cava, portal vein). The aim of the present study was to analyse the role of surgical resection (SR) and loco regional therapy (LRT) in these advanced stage patients to determine if there was a survival benefit. METHODS: The study is a retrospective analysis from the Commission on Cancer's National Cancer Data Base (NCDB) from 1998 to 2011. In total, 148,882 patients with liver cancer were identified, of which 126,984 had HCC. Of these, 64,264 patients (1998-2006) had 5-year survival data available and 8825 patients had Stage 3A disease based on AJCC classification. Of these patients, 884 had SR, 771 had LRT and 7170 patients had neither intervention. Kaplan-Meier curves and log-rank tests were used for statistical analysis. RESULTS: Eight thousand eight hundred and twenty-five patients met analysis criteria. The mean age (years) in the SR, LRT and no intervention group were 62.5, 64.3 and 64.2, respectively. Most patients were males in all three groups (77.5%, 74.5% and 68.1%). The mean tumour size (cm) in the three groups was 9.8, 6.4 and 8.4, respectively. SR and LRT were primarily performed in major academic and comprehensive cancer programmes compared with community cancer programmes and other centres (SR: 93% versus 7%; LRT: 94.6% versus 5.4%). The median 5-year survival (months) was 26.6 in SR, 16.5 in LRT and 4.8 in the no intervention group (P < 0.0001). CONCLUSION: A SR and LRT offer a survival benefit in select patients diagnosed with Stage 3A HCC. PMID- 26271741 TI - Microbiome Variation Across Amphibian Skin Regions: Implications for Chytridiomycosis Mitigation Efforts. AB - Cutaneous bacteria may play an important role in the resistance of amphibians to the pathogenic fungus Batrachochytrium dendrobatidis (Bd). Microbial communities resident on hosts' skin show topographical diversity mapping to skin features, as demonstrated by studies of the human microbiome. We examined skin microbiomes of wild and captive fire-bellied toads (Bombina orientalis) for differences across their body surface. We found that bacterial communities differed between ventral and dorsal skin. Wild toads showed slightly higher bacterial richness and diversity in the dorsal compared to the ventral region. On the other hand, captive toads hosted a higher richness and diversity of bacteria on their ventral than their dorsal skin. Microbial community composition and relative abundance of major bacterial taxonomic groups also differed between ventral and dorsal skin in all populations. Furthermore, microbiome diversity patterns varied as a function of their Bd infection status in wild toads. Bacterial richness and diversity was greater, and microbial community structure more complex, in wild than captive toads. The results suggest that bacterial community structure is influenced by microhabitats associated with skin regions. These local communities may be differentially modified when interacting with environmental bacteria and Bd. A better understanding of microbiome variation across skin regions will be needed to assess how the skin microbiota affects the abilities of amphibian hosts to resist Bd infection, especially in captive breeding programs. PMID- 26271744 TI - Simulating the fate and transport of nursery-box-applied pesticide in rice paddy fields. AB - BACKGROUND: The Pesticide Concentration in a Paddy Field model (PCPF-1) was modified by adding a root zone compartment to simulate nursery-box-applied (NB applied) pesticide. The PCPF-NB model was validated for predicting the concentrations of NB-applied fipronil and imidacloprid in rice paddy fields using two treatment methods: before transplanting (BT) and at sowing (AS). Uncertainty and sensitivity analyses were used to evaluate the robustness of the concentrations predicted by the model. RESULTS: The hourly predicted concentrations of imidacloprid and fipronil were accurate in both paddy water and 1 cm deep paddy soil. The coefficient of determination and Nash-Sutcliffe model efficiency were greater than 0.87 and 0.60 respectively. The 95th percentiles of the predicted concentrations of fipronil and imidacloprid indicated that the influence of input uncertainty was minor in paddy water but important in paddy soil. The pesticide deposition rate and the desorption rate from the root zone were identified to be the major contributors to the variation in the predicted concentrations in paddy water and soil. CONCLUSION: The PCPF-NB model was validated for predicting the fate and transport of NB-applied fipronil and imidacloprid using the BT and AS treatment methods. (c) 2015 Society of Chemical Industry. PMID- 26271745 TI - Chronic institutional failure and enhanced vulnerability to flash-floods in the Cuenca Altadel Rio Lerma, Mexico. AB - The dominant paradigm in disaster risk reduction (DRR) policies has been seriously contested because of its reliance on interventions based on technocratic expertise. In the Mexican context, the influence of informal practices such as clientelism and cartelisation of the political system produces environmental degradation and vulnerability to disasters within the communities in the study site. This paper contributes to understanding of failed institutional processes and parallel practices that intensify vulnerability to disasters by contrasting the discourses of agents within a peri-urban community in central Mexico. Employing the Situational Analysis Approach as a methodological framework, the study identifies divergent views and practices within the community, leading to different responses to disasters and to different perceptions regarding institutional performance. In addition, it finds that institutional decision-making, based only on scientific and technical expertise, has resulted in unintended consequences that influence ongoing vulnerability to floods in the site under review. PMID- 26271747 TI - Assessment of contamination using an ATP bioluminescence assay on doorknobs in a university-affiliated hospital in Japan. AB - BACKGROUND: Doorknobs are inevitable points of hand contact. We monitored doorknob contamination in a university hospital using an ATP bioluminescence assay and stamp agar method. We selected grip-, lever-, push-, insert-, and two pull-type doorknobs in staff lavatories and break rooms, a linen closet, dirty utility rooms, a newborn care unit, clinical lavatories and examination rooms, dressing rooms for radiological tests, and lavatories for health examination, as monitoring points in wards and clinics. Sequential monitoring with an ATP assay (six times) and culture (once) were performed at the same time of day in autumn, winter, and summer. We provided contamination data to appropriate healthcare providers and housekeepers, and queried the staff regarding decontamination of doorknobs. RESULTS: When comparing ATP values on the same type of doorknobs, significant differences in contamination were demonstrated among several clinical rooms and several rooms in wards during all three seasons. No correlation was observed between ATP values on clinical-examination-room doorknobs and outpatient numbers, or between ATP values at any monitoring point and microbial colony forming units. ATP values on clinical-examination-room doorknobs were reduced after cleaning according to instructions. CONCLUSIONS: ATP assay is useful for measuring baseline doorknob contamination in clinical rooms. Our findings confirm the need to improve routine decontamination in clinical departments. We need to analyze further the relationship between hospital-acquired infections and doorknob contamination, as assessed by ATP assay in clinics. PMID- 26271748 TI - Are daylight saving time transitions associated with changes in myocardial infarction incidence? Results from the German MONICA/KORA Myocardial Infarction Registry. AB - BACKGROUND: Some studies suggest that transitions to and from daylight saving time (DST) have an influence on acute myocardial infarction (AMI) incidence. However, the available publications have a number of limitations e.g. regarding sample size, exclusion of fatal AMI cases, precise assessment of AMI onset, and consideration of possible confounders, and they were conducted in countries with different geographical location. The objective of this study was to examine the association of DST transitions with AMI incidence recorded in the population based German MONICA/KORA Myocardial Infarction Registry. METHODS: The study sample consisted of 25,499 coronary deaths and non-fatal AMI cases aged 25-74 years. We used Poisson regression with indicator variables for the 3 days or the week after the spring and the autumn transition and adjusted for potential confounders to model the association between DST transitions and AMI incidence. In addition, we built an excess model by calculating observed over expected events per day. RESULTS: Overall, no significant changes of AMI risk during the first 3 days or 1 week after the transition to and from DST were found. However, subgroup analyses on the spring transition revealed significantly increased risks for men in the first 3 days after transition (RR 1.155, 95 % CI 1.000-1.334) and for persons who took angiotensine converting enzyme (ACE) inhibitors prior to the AMI (3 days: RR 1.489, 95 % CI 1.151-1.927; 1 week: RR 1.297, 95 % CI 1.063 1.582). After the clock shift in autumn, patients with a prior infarction had an increased risk to have a re-infarction (3 days: RR 1.319, 95 % CI 1.029-1.691; 1 week: RR 1.270, 95 % CI 1.048-1.539). CONCLUSIONS: Specific subgroups such as men and persons with a history of AMI or prior treatment with ACE inhibitors, may have a higher risk for AMI during DST. Further studies which include data on chronotype and sleep duration are needed in order to confirm these results. PMID- 26271746 TI - Transcriptional maturation of the mouse auditory forebrain. AB - BACKGROUND: The maturation of the brain involves the coordinated expression of thousands of genes, proteins and regulatory elements over time. In sensory pathways, gene expression profiles are modified by age and sensory experience in a manner that differs between brain regions and cell types. In the auditory system of altricial animals, neuronal activity increases markedly after the opening of the ear canals, initiating events that culminate in the maturation of auditory circuitry in the brain. This window provides a unique opportunity to study how gene expression patterns are modified by the onset of sensory experience through maturity. As a tool for capturing these features, next generation sequencing of total RNA (RNAseq) has tremendous utility, because the entire transcriptome can be screened to index expression of any gene. To date, whole transcriptome profiles have not been generated for any central auditory structure in any species at any age. In the present study, RNAseq was used to profile two regions of the mouse auditory forebrain (A1, primary auditory cortex; MG, medial geniculate) at key stages of postnatal development (P7, P14, P21, adult) before and after the onset of hearing (~P12). Hierarchical clustering, differential expression, and functional geneset enrichment analyses (GSEA) were used to profile the expression patterns of all genes. Selected genesets related to neurotransmission, developmental plasticity, critical periods and brain structure were highlighted. An accessible repository of the entire dataset was also constructed that permits extraction and screening of all data from the global through single-gene levels. To our knowledge, this is the first whole transcriptome sequencing study of the forebrain of any mammalian sensory system. Although the data are most relevant for the auditory system, they are generally applicable to forebrain structures in the visual and somatosensory systems, as well. RESULTS: The main findings were: (1) Global gene expression patterns were tightly clustered by postnatal age and brain region; (2) comparing A1 and MG, the total numbers of differentially expressed genes were comparable from P7 to P21, then dropped to nearly half by adulthood; (3) comparing successive age groups, the greatest numbers of differentially expressed genes were found between P7 and P14 in both regions, followed by a steady decline in numbers with age; (4) maturational trajectories in expression levels varied at the single gene level (increasing, decreasing, static, other); (5) between regions, the profiles of single genes were often asymmetric; (6) GSEA revealed that genesets related to neural activity and plasticity were typically upregulated from P7 to adult, while those related to structure tended to be downregulated; (7) GSEA and pathways analysis of selected functional networks were not predictive of expression patterns in the auditory forebrain for all genes, reflecting regional specificity at the single gene level. CONCLUSIONS: Gene expression in the auditory forebrain during postnatal development is in constant flux and becomes increasingly stable with age. Maturational changes are evident at the global through single gene levels. Transcriptome profiles in A1 and MG are distinct at all ages, and differ from other brain regions. The database generated by this study provides a rich foundation for the identification of novel developmental biomarkers, functional gene pathways, and targeted studies of postnatal maturation in the auditory forebrain. PMID- 26271749 TI - Is There a Role for Oncotype Dx Testing in Invasive Lobular Carcinoma? AB - Oncotype Dx Breast Cancer Assay is a 21-gene assay used in estrogen receptor (ER) positive breast cancer to predict benefit from chemotherapy (CT). Tumors are placed into one of three risk categories based on their recurrence score (RS). This paper explores the impact of tumor histopathologic features and Oncotype Dx RS on the treatment plan for invasive lobular carcinoma (ILC). Invasive lobular carcinoma cases submitted for Oncotype Dx testing were identified from a clinical data base. The histopathologic and immunohistochemical features and RS subcategory of each tumor, and treatment regimen and medical oncologic assessments of each patient were reviewed. A total of 135 cases of ILC had RS testing, which represented 15% of all ILC diagnosed at the institution over the time period. 80% of ILC was of the classical subtype and all tumors were ER positive and human epidermal growth factor receptor 2 (HER-2) negative by immunohistochemistry. Sixty three percent of cases were low risk (LR), 35.5% were intermediate risk (IR) and 1.5% were high risk (HR). Both HR cases were pleomorphic ILC. Sixty eight percent of classical ILC had a LR score, while 70% of pleomorphic ILC had an IR score. Patients in the IR category were significantly more likely to undergo CT than patients in the LR category (54% versus 18%; p < 0.0001). In the LR category, those undergoing CT were significantly younger and more likely to have positive lymph nodes (p < 0.05). Qualitative analysis of medical oncologic assessments showed that RS played a role in decision-making on CT in 74% of cases overall. At our institution, Oncotype Dx RS currently plays a role in the management of a proportion of ILC and impacts on treatment decisions. PMID- 26271750 TI - Changes in microbiota during experimental human Rhinovirus infection. AB - BACKGROUND: Human Rhinovirus (HRV) is responsible for the majority of common colds and is frequently accompanied by secondary bacterial infections through poorly understood mechanisms. We investigated the effects of experimental human HRV serotype 16 infection on the upper respiratory tract microbiota. METHODS: Six healthy volunteers were infected with HRV16. We performed 16S ribosomal RNA targeted pyrosequencing on throat swabs taken prior, during and after infection. We compared overall community diversity, phylogenetic structure of the ecosystem and relative abundances of the different bacteria between time points. RESULTS: During acute infection strong trends towards increases in the relative abundances of Haemophilus parainfluenzae and Neisseria subflava were observed, as well as a weaker trend towards increases of Staphylococcus aureus. No major differences were observed between day-1 and day 60, whereas differences between subjects were very high. CONCLUSIONS: HRV16 infection is associated with the increase of three genera known to be associated with secondary infections following HRV infections. The observed changes of upper respiratory tract microbiota could help explain why HRV infection predisposes to bacterial otitis media, sinusitis and pneumonia. PMID- 26271752 TI - End-of-life decision-making for newborns: a 12-year experience in Hong Kong. AB - SETTING: Neonatal end-of-life decisions could be influenced by cultural and ethnic backgrounds. These practices have been well described in the West but have not been systematically studied in an Asian population. OBJECTIVES: To determine: (1) different modes of neonatal death and changes over the past 12 years and (2) factors influencing end-of-life decision-making in Hong Kong. DESIGN: A retrospective study was conducted to review all death cases from 2002 to 2013 in the busiest neonatal unit in Hong Kong. Modes of death, demographical data, diagnoses, counselling and circumstances around the time of death, were collected and compared between groups. RESULTS: Of the 166 deaths, 46% occurred despite active resuscitation (group 1); 35% resulted from treatment withdrawal (group 2) and 19% occurred from withholding treatment (group 3). A rising trend towards treatment withdrawal was observed, from 20% to 47% over the 12-year period. Similar number of parents chose extubation (n=44, 27%) compared with other modalities of treatment limitation (n=45, 27%). Significantly more parents chose to withdraw rather than to withhold treatment if clinical conditions were 'stable' (p=0.03), whereas more parents chose withholding therapy if treatment was considered futile (p=0.03). CONCLUSION: In Hong Kong, a larger proportion of neonatal deaths occurred despite active resuscitation compared with Western data. Treatment withdrawal is, however, becoming increasingly more common. Unlike Western practice, similar percentages of parents chose other modalities of treatment limitation compared with direct extubation. Cultural variance could be a reason for the different end-of-life practice adopted in Hong Kong. PMID- 26271751 TI - Simultaneous Detection of Androgen and Estrogen Abuse in Breeding Animals by Gas Chromatography-Mass Spectrometry/Combustion/Isotope Ratio Mass Spectrometry (GC MS/C/IRMS) Evaluated against Alternative Methods. AB - The administration of synthetic homologues of naturally occurring steroids can be demonstrated by measuring (13)C/(12)C isotopic ratios of their urinary metabolites. Gas chromatography-mass spectrometry/combustion/isotope ratio mass spectrometry (GC-MS/C/IRMS) was used in this study to appraise in a global approach isotopic deviations of two 17beta-testosterone metabolites (17alpha testosterone and etiocholanolone) and one 17beta-estradiol metabolite (17alpha estradiol) together with those of 5-androstene-3beta,17alpha-diol as endogenous reference compound (ERC). Intermediate precisions of 0.350/00, 1.050/00, 0.350/00, and 0.210/00, respectively, were observed (n = 8). To assess the performance of the analytical method, a bull and a heifer were treated with 17beta-testosterone propionate and 17beta-estradiol-3-benzoate. The sensitivity of the method permitted the demonstration of 17beta-estradiol treatment up to 24 days. For 17beta-testosterone treatment, the detection windows were 3 days and 24 days for the bull and the heifer, respectively. The capability of GC-MS/C/IRMS to demonstrate natural steroid abuse for urinary steroids was eventually compared to those of mass spectrometry (LC-MS/MS) when measuring intact steroid esters in blood and hair. PMID- 26271754 TI - An atom-scale interfacial coordination strategy to prepare hierarchically porous Fe3O4-graphene frameworks and their application in charge and size selective dye removal. AB - A novel atom-scale interfacial coordination assisted synthesis method for the textural engineering of three-dimensional (3D) Fe3O4-graphene oxide frameworks with hierarchical macro- and meso-porous structures is developed. PMID- 26271753 TI - A randomised controlled trial of flow driver and bubble continuous positive airway pressure in preterm infants in a resource-limited setting. AB - OBJECTIVES: The variable-flow flow driver (FD; EME) and continuous-flow bubble (Fisher-Paykel) continuous positive airway pressure (CPAP) systems are widely used. As these differ in cost and technical requirements, determining comparative efficacy is important particularly where resources are limited. DESIGN: We performed a randomised, controlled, equivalence trial of CPAP systems. We specified the margin of equivalence as 2 days. We analysed binary variables by logistical regression adjusted for gestation, and log transformed continuous variables by multiple linear regression adjusted for gestation, sex and antenatal steroids. SETTING: A neonatal unit with no blood gas analyser or surfactant availability and limited X-ray and laboratory facilities PATIENTS: Neonates <37 weeks of gestation. INTERVENTIONS: We provided CPAP at delivery followed by randomisation to FD or bubble (B). OUTCOMES: Primary outcome included total days receiving CPAP; secondary outcomes included days receiving CPAP, supplemental oxygen, ventilation, death, pneumothorax and nasal excoriation. RESULTS: We randomised 125 infants (B 66, FD 59). Differences in infant outcomes on B and FD were not statistically significant. The median (range) for CPAP days for survivors was B 0.8 (0.04 to 17.5), FD 0.5 (0.04 to 5.3). B:FD (95% CI) ratios were CPAP days 1.3 (0.9 to 2.1), CPAP plus supplementary oxygen days 1.2 (0.7 to 1.9). B:FD (95% CI) ORs were death 2.3 (0.2 to 28), ventilation 2.1 (0.5 to 9), nasal excoriation 1.2 (0.2 to 8) and pneumothorax 2.4 (0.2 to 26). CONCLUSIONS: In a resource-limited setting we found B CPAP equivalent to FD CPAP in the total number of days receiving CPAP within a margin of 2 days. TRIAL REGISTRATION NUMBER: ISRCTN22578364. PMID- 26271757 TI - The Opioid Epidemic: Impact on Orthopaedic Surgery. PMID- 26271756 TI - Low Back Pain and Pelvic Girdle Pain in Pregnancy. AB - Pregnancy has a profound effect on the human body, particularly the musculoskeletal system. Hormonal changes cause ligamentous joint laxity, weight gain, and a shift in the center of gravity that leads to lumbar spine hyperlordosis and anterior tilting of the pelvis. In addition, vascular changes may lead to compromised metabolic supply in the low back. The most common musculoskeletal complaints in pregnancy are low back pain and/or pelvic girdle pain. They can be diagnosed and differentiated from each other by history taking, clinical examination, provocative test maneuvers, and imaging. Management ranges from conservative and pharmacologic measures to surgical treatment. Depending on the situation, and given the unique challenges pregnancy places on the human body and the special consideration that must be given to the fetus, an orthopaedic surgeon and the obstetrician may have to develop a plan of care together regarding labor and delivery or when surgical interventions are indicated. PMID- 26271755 TI - Saving lives, maintaining safety, and science-based policy: qualitative interview findings from the Blood Donation Rules Opinion Study (Blood DROPS). AB - BACKGROUND: Indefinite deferral from donation for any man who discloses having had sex with another man even once since 1977 (MSM77) is the US FDA's standing policy. This qualitative component of the Blood Donation Rules and Opinion Study was designed to provide insight into the perceptions and practices of current or previous donors with MSM history. STUDY DESIGN AND METHODS: Forty human immunodeficiency virus (HIV)-negative MSM completed an online survey, indicating that they had donated blood and were willing to be interviewed. Semistructured, individual interviews with these key informants covered donation experience and motivations, perceptions of MSM77, policy change preferences, and possible impact of a change to a time-limited deferral. Transcripts were coded deductively and inductively, following a modified Grounded Theory approach. Analysis identified recurrent and divergent themes. RESULTS: Ninety-five percent of participants endorsed modifying MSM77. Preferred deferral length ranged from none to 5 years; a common opinion was that a science-based deferral period would be less than 1 year. Other policy change recommendations included incorporating questions about specific HIV risk behaviors to the donor questionnaire for all potential donors. Interviewees recognized HIV infection rates are higher in MSM than the general US population, but participants considered themselves low-risk for HIV, donated blood "to save lives," and justified their recommendations as being more effective ways to identify donors at risk for HIV. CONCLUSION: Results suggest that MSM donors are concerned with blood safety; they can be appealed to as such. Communications about a new deferral policy should include scientific explanations and acknowledge altruistic motivations of potential donors. PMID- 26271758 TI - Pediatric Knee Dislocations and Physeal Fractures About the Knee. AB - Given the high incidence of vascular and neurologic injury associated with pediatric knee dislocations and displaced physeal injuries about the knee, a thorough understanding of the clinical and radiographic signs associated with these injuries, relevant anatomy, workup, reduction techniques, and surgical management is crucial. A higher incidence of these injuries in children is anticipated because of increased participation in high-energy activities that result in contact or collision during sports or recreation. Complications, such as vascular and nerve injuries and compartment syndrome, can be diagnosed early in the workup to prevent catastrophic outcomes. The clinical examination should include evaluation of the motor and sensory status of the limb, palpation of pulses, and measurement of ankle brachial indices. Radiographic examination should include plain radiography and supplemental advanced imaging, if indicated. Vascular imaging or expert consultation should be considered when the pulse or ankle brachial index is abnormal on clinical examination. Selection of nonsurgical or surgical treatment depends on the fracture pattern and stability. PMID- 26271760 TI - Every base matters: assessing small subunit rRNA primers for marine microbiomes with mock communities, time series and global field samples. AB - Microbial community analysis via high-throughput sequencing of amplified 16S rRNA genes is an essential microbiology tool. We found the popular primer pair 515F (515F-C) and 806R greatly underestimated (e.g. SAR11) or overestimated (e.g. Gammaproteobacteria) common marine taxa. We evaluated marine samples and mock communities (containing 11 or 27 marine 16S clones), showing alternative primers 515F-Y (5'-GTGYCAGCMGCCGCGGTAA) and 926R (5'-CCGYCAATTYMTTTRAGTTT) yield more accurate estimates of mock community abundances, produce longer amplicons that can differentiate taxa unresolvable with 515F-C/806R, and amplify eukaryotic 18S rRNA. Mock communities amplified with 515F-Y/926R yielded closer observed community composition versus expected (r(2) = 0.95) compared with 515F-Y/806R (r(2) ~ 0.5). Unexpectedly, biases with 515F-Y/806R against SAR11 in field samples (~4-10-fold) were stronger than in mock communities (~2-fold). Correcting a mismatch to Thaumarchaea in the 515F-C increased their apparent abundance in field samples, but not as much as using 926R rather than 806R. With plankton samples rich in eukaryotic DNA (> 1 MUm size fraction), 18S sequences averaged ~17% of all sequences. A single mismatch can strongly bias amplification, but even perfectly matched primers can exhibit preferential amplification. We show that beyond in silico predictions, testing with mock communities and field samples is important in primer selection. PMID- 26271761 TI - Association of dopamine receptor D2 TaqI A polymorphism and cannabis use disorder in Lagos, Nigeria. AB - TaqI A polymorphism (rs1800497) has been linked to many substance use disorders but there is a shortage of data on cannabis use disorder. Nigeria has a huge burden of cannabis use disorder, prompting our investigation of the relation between cannabis use disorder and the TaqI A polymorphism among males in Lagos, Nigeria. We recruited 106 males with cannabis use disorder based on International Classification of Diseases, version 10 (ICD-10) and 98 cannabis-naive males for the study. Cannabis use disorder was assessed using the Severity of Dependence Scale (SDS) and Cannabis Use Disorder Identification Test (CUDIT). Genotyping was done using the Restriction Fragment Length Polymorphism (RFLP). The frequency of the A1 allele was higher among the cannabis users (57.8%) compared with the nonusers (42.2%). The genotype distribution was found to be in Hardy-Weinberg equilibrium in both populations. The homozygous A1 genotype alone contributed 11.8% to the variance in the SDS scores. However, both A1/A1 and A1/A2 genotypes contributed to the variance in the CUDIT scores (10.2% and 5.1%, respectively). In conclusion, the distribution of the A1 allele among the general population in this study correlates with the previously reported findings in a southwestern Nigerian population. We also found that carrying an A1 allele appears to be a significant predictor of cannabis use disorder. The result suggests that carrying just a single allele of the A1 is enough to predict cannabis abuse, as shown by the allele association with CUDIT scores. However, double A1 alleles seem to be necessary for the prediction of dependence. PMID- 26271759 TI - Perioperative Treatment of Patients with Rheumatoid Arthritis. AB - Rheumatoid arthritis is an autoimmune disease mediated by a widespread chronic systematic inflammatory process that causes joint deterioration, which leads to pain, disability, and poor quality of life. The increased use of disease modifying antirheumatic drugs has been shown to markedly slow disease progression, which has translated into a decrease in the need for orthopaedic intervention in this population. However, a substantial percentage of patients with the disease fail optimal pharmacologic treatment and still require surgical intervention. A thorough understanding of medical considerations in these patients and improved knowledge of the medical complications caused by the disease process and the pharmacologic therapy used to treat it may lead to improved preoperative planning and medical clearance, which may ultimately improve the overall postoperative outcome. PMID- 26271762 TI - Developing a Chinese PTSD Inventory (CPI) based on interviews with earthquake victims in Sichuan. AB - Although some of the self-report scales for posttraumatic stress disorder (PTSD) are available in Chinese and are currently in use in China, cultural limitations exist. An indigenous Chinese PTSD self-rating scale-the Chinese PTSD Inventory (CPI)-has been developed. The item generation of the CPI was based on interviews of Sichuan earthquake victims. Exploratory factor analysis was conducted on a sample of 313 earthquake victims, acquiring five factors with 27 items: Intrusion, Avoidance, Hyperarousal, Dysphoria, and Somatization. Another sample of 227 debris-flow victims was administered the 27-item CPI. It demonstrated high internal consistency and test-retest reliability, and the result of confirmatory factor analysis indicated a good fit for the five-factor model. PMID- 26271764 TI - Single and aggregate salivary cortisol measures during two schooldays in midadolescent girls and boys. AB - The hypothalamic-pituitary-adrenal (HPA) axis, including its regulation of cortisol, is central to bodily functioning and salivary cortisol is a commonly used biomarker that reflects the functioning of the HPA axis. However, knowledge of diurnal cortisol rhythms in healthy adolescents is limited and few studies have examined patterns in midadolescent girls and boys across single and aggregate cortisol measures. To fill this gap, the present study investigated single and aggregate cortisol measures reflecting diurnal rhythms in 14 to 16 year-old girls and boys. Self-administered salivary samples from 79 girls and 42 boys were collected during two schooldays at four timepoints: (a) immediately at awakening, (b) 30 min after waking up, (c) 60 min after waking up, and (d) at 8:00 p.m. Additionally, diary data including time of awakening, sampling times, and other potential confounders were analyzed. As for single measures, both girls and boys exhibited a typical diurnal cortisol profile with high levels in the morning that decreased throughout the day. However, girls had higher morning cortisol than did boys with significant differences at time of awakening, and at 30 and 60 min postawakening. For the aggregate measures, girls had a larger total level of cortisol in terms of cortisol awakening response (CARG ), area under the curve (AUCG ), and rise over run (slopeawake to last ), while no differences emerged for reactivity measures. Taken together, these findings suggest differences in single and aggregate cortisol measures between midadolescent girls and boys. Such differences in diurnal cortisol between pubertal girls and boys may play a role for the differential health trajectories typically found among adult women and men. PMID- 26271763 TI - Voice-associated static face image releases speech from informational masking. AB - In noisy, multipeople talking environments such as a cocktail party, listeners can use various perceptual and/or cognitive cues to improve recognition of target speech against masking, particularly informational masking. Previous studies have shown that temporally prepresented voice cues (voice primes) improve recognition of target speech against speech masking but not noise masking. This study investigated whether static face image primes that have become target-voice associated (i.e., facial images linked through associative learning with voices reciting the target speech) can be used by listeners to unmask speech. The results showed that in 32 normal-hearing younger adults, temporally prepresenting a voice-priming sentence with the same voice reciting the target sentence significantly improved the recognition of target speech that was masked by irrelevant two-talker speech. When a person's face photograph image became associated with the voice reciting the target speech by learning, temporally prepresenting the target-voice-associated face image significantly improved recognition of target speech against speech masking, particularly for the last two keywords in the target sentence. Moreover, speech-recognition performance under the voice-priming condition was significantly correlated to that under the face-priming condition. The results suggest that learned facial information on talker identity plays an important role in identifying the target-talker's voice and facilitating selective attention to the target-speech stream against the masking-speech stream. PMID- 26271765 TI - Emotional well-being and time pressure. AB - We propose a conceptual model of how time pressure affects emotional well-being associated with mundane routine activities. A selective review of research in several areas affirms the plausibility of the conceptual model, which posits negative effects on emotional well-being of insufficient time allocated to restorative and other activities instrumental for attaining desirable work, family life, and leisure goals. Previous research also affirms that practicing time management can have indirect positive effects by decreasing time pressure, whereas material wealth can have both negative indirect effects and positive indirect effects by increasing and decreasing time pressure, respectively. Several issues remain to be studied empirically. The conceptual model is a ground for additional, preferably cross-cultural, research. PMID- 26271767 TI - In support of a hot hand in professional basketball and baseball. AB - Recent studies have found little empirical evidence to suggest that National Basketball Association (NBA) and Major League Baseball (MLB) players have hot streaks. This has led some to suggest that hot hands do not exist and that offensive and defensive strategies adjusting to perceived hot hands are suboptimal. We study the MLB's Home Run Derby and the NBA's 3-point Shootout. When there is no defense, extended time between shots has been removed, and shot or swing selection is constant, we find evidence that player performance is nonstationary. Our results are consistent with beliefs long held by players, coaches, and fans, research on the importance of self-efficacy in sports, and studies that support the existence of hot streaks in sports with no or limited defense. PMID- 26271766 TI - Mental health literacy: Public knowledge and beliefs about mental disorders in mainland China. AB - This study was concerned with the general mental health literacy of lay people in mainland China. It replicates in part many studies done in America, Australia, and Europe. A total of 212 participants were asked to read vignettes depicting people with schizophrenia, obsessive-compulsive disorder, social phobia, depression, bipolar disorder, stress, child attention-deficit hyperactivity disorder (ADHD), child depression, and child "daily troubles." For each vignette they were asked to label the vignette character's main problem, to evaluate various suggestions for helping that person, to rate their attitudes towards the character, and finally their confidence in all their responses. Overall ADHD was the best identified, and bipolar disorder and stress were the least frequently identified mental health disorders. Professional help from a psychologist/psychiatrist was most frequently endorsed for all disorders, which was followed by help from parents or friends. No significant correlation was found between psychological knowledge and "correct" recognition as defined by the psychiatric label. The findings were discussed in relation to the Chinese language and culture, social beliefs about mental disorders, and suggestions for improvements in mental health literacy. Limitations of this study were also acknowledged, particularly with respect to sampling. Suggestions for future work research were considered. PMID- 26271768 TI - The hot hand belief as an inference of local temporal instability. AB - The correspondence article (Shea, 2013, "In support of a hot hand...") examines MLB's Home Run Derby and the NBA's 3-point Shootout data, and reveals nonstationarity as empirical evidence supporting the hot hand belief. This result, together with recent understanding on human probabilistic reasoning with sparse data, suggests that the hot hand belief may have been driven by local and temporal instability in the task environment. We argue that computational models of the hot hand belief should take into consideration not only top-down cognitive biases but also the statistical structures of the task environment, where global structures evolve from intrinsically local properties centered on temporal instability. PMID- 26271769 TI - Dose-response relationship between light exposure and cycling performance. AB - Light has a stimulating effect on physical performance if scheduled according to the chronotype, but dose-dependent effects on performance have not yet been examined. Three groups of healthy men (25.1 +/- 3.1 years) were exposed to light for different durations in a parallel group design before a 40-min time-trial. In each group, subjects were exposed to either bright light (BL, 4420 lx) or moderate light (ML, 230 lx) in a randomized order in a crossover design. The durations of light exposure were 120 min prior to and during exercise (2HEX; n = 16), 60 min prior to and during exercise (1HEX; n = 10), or only for 60 min prior to exercise (1H; n = 15). Total work performed during the time-trial in kJ in the 2HEX group was significantly higher in the BL setting (527 kJ) than in ML (512 kJ) (P = 0.002), but not in 1HEX (BL: 485 kJ; ML: 498 kJ) or 1H (BL: 519 kJ; ML: 514 kJ) (P = 0.770; P = 0.485). There was a significant (P = 0.006) positive dose response relationship between the duration of light exposure and the work performed over the three doses of light exposure. A long duration light exposure is an effective tool to increase total work in a medium length time-trial in subjects normalized for their individual chronotype. PMID- 26271771 TI - Supply Chain Vulnerability Analysis Using Scenario-Based Input-Output Modeling: Application to Port Operations. AB - Disruptive events such as natural disasters, loss or reduction of resources, work stoppages, and emergent conditions have potential to propagate economic losses across trade networks. In particular, disruptions to the operation of container port activity can be detrimental for international trade and commerce. Risk assessment should anticipate the impact of port operation disruptions with consideration of how priorities change due to uncertain scenarios and guide investments that are effective and feasible for implementation. Priorities for protective measures and continuity of operations planning must consider the economic impact of such disruptions across a variety of scenarios. This article introduces new performance metrics to characterize resiliency in interdependency modeling and also integrates scenario-based methods to measure economic sensitivity to sudden-onset disruptions. The methods will be demonstrated on a U.S. port responsible for handling $36.1 billion of cargo annually. The methods will be useful to port management, private industry supply chain planning, and transportation infrastructure management. PMID- 26271772 TI - Simultaneous heavy metals removal and municipal sewage sludge dewaterability improvement in bioleaching processes by various inoculums. AB - The heavy metals content and dewaterability of municipal sewage sludge (MSS) are important parameters affecting its subsequent disposal and land application. Six kinds of inoculums were prepared to examine the characteristics of heavy metals removal and MSS dewaterability improvement in bioleaching processes. The results showed that Cu, Zn and Cd bioleaching efficiencies (12 days) were 81-91, 87-93 and 81-89%, respectively, which were significantly higher than those of Fe-S control (P < 0.05) and blank control (P < 0.01). The bioleaching boosted by the prepared inoculums could also significantly enhance MSS dewaterability (P < 0.01). The centrifugal dehydration efficiency of MSS rose from 73.00 to 90.00% at day 12. Microscopic observations and energy dispersive spectrum analysis demonstrated that the dewaterability improvement might be attributed to the changes of sludge structure from flocculent to obvious granular and the formation of secondary minerals mainly consisting of iron, oxygen and sulfur elements. The results above demonstrated that bacterial consortium enriched from acid mine drainage (AMD) was suitable to boost sludge bioleaching for heavy metals removal and dewaterability improvement. It also suggested that the synergy of sulfur/ferrous-oxidizing bacteria (SFOB) enriched from AMD and the cooperation of exogenous and indigenous SFOB significantly promoted bioleaching efficiencies. PMID- 26271770 TI - Comparison of clinical outcome between laparoscopic and open right hemicolectomy: a nationwide study. AB - BACKGROUND: This study aimed to compare clinical outcome between laparoscopic and open right hemicolectomy. METHODS: The data were sourced from Taiwan's National Health Insurance Research Database. This study included 14,320 and 1313 patients who underwent open and laparoscopic right hemicolectomies, respectively. The study outcome included "intensive care unit (ICU) admission," "over 2 h of general anesthesia," "use of mechanical ventilation," "acute respiratory failure," "in-hospital death," and "hospitalization for pneumonia." Separate conditional logistic regressions were performed for each clinical outcome. RESULTS: The results showed that patients who underwent an open right hemicolectomy had significantly higher likelihood of ICU admission (31.4 vs. 13.4%, p<0.001), acute respiratory failure (3.6 vs. 0.8%, p<0.001), mechanical ventilation (12.8 vs. 4.1%, p<0.001), in-hospital death (3.7 vs. 0.9%, p<0.001), over 2 h of general anesthesia (4.6 vs. 1.2%, p<0.001), and hospitalization for pneumonia (5.8 vs. 3.1%, p<0.001) than patients who underwent a laparoscopic right hemicolectomy. Adjusted conditional logistic regression analyses revealed that patients who underwent an open right hemicolectomy were 2.96, 4.98, 3.41, 4.01, 3.44, and 1.78 times more likely to be admitted to the ICU, to have acute respiratory failure, the use of mechanical ventilation, in-hospital death, over 2 h of general anesthesia, and hospitalization for pneumonia, respectively, than patients who underwent a laparoscopic right hemicolectomy. CONCLUSIONS: Laparoscopic right hemicolectomy reduced risk of post-operative pulmonary complications. PMID- 26271773 TI - Investigation of lead(II) uptake by Bacillus thuringiensis 016. AB - In this work, we investigated the lead(II) biosorption mechanism of Bacillus thuringiensis (Bt) 016 through batch and microscopic experiments. We found that the maximum lead(II) biosorption capacity of Bt 016 was 164.77 mg/g (dry weight). The pH value could affect the biosorption of lead(II) in a large extent. Fourier transform infrared analyses and selective passivation experiments suggested that the carboxyl, amide and phosphate functional groups of Bt 016 played an important role in lead(II) biosorption. Scanning electron microscopy observation showed that noticeable lead(II) precipitates were accumulated on bacterial surfaces. Further transmission electron microscopy thin section analysis coupled with energy dispersive X-ray spectroscopy as well as selected area electron diffraction indicated that lead(II) immobilized on the bacteria could be transformated into random-shaped crystalline lead-containing minerals eventually. This work provided a new insight into lead(II) uptake of Bt, highlighting the potential of Bt in the restoration of lead(II) contaminated repositories. PMID- 26271774 TI - Vision, Identity, and Career in the Clinical and Translational Sciences: Building upon the Formative Years. AB - This paper is the second in a five-part series on the clinical and translational science educational pipeline. It focuses on the role that Clinical and Translational Science Award (CTSA) programs can play in supporting science, technology, engineering, and math (STEM) education in primary and secondary schools, as well as in facilitating these interests during transition to undergraduate training. Special emphasis should be placed on helping to form and sustain an identity as a scientist, and on instilling the persistence necessary to overcome numerous barriers to its actualization. CTSAs can contribute to cementing this sense of self by facilitating peer support, mentorship, and family involvement that will reinforce early educational decisions leading to clinical and translational science research careers. Meanwhile, the interests, skills, and motivation induced by participation in STEM programs must be sustained in transition to the next level in the educational pipeline, typically undergraduate study. Examples of CTSA collaborations with local schools, businesses, interest groups, and communities at large illustrate the emerging possibilities and promising directions with respect to each of these challenges. PMID- 26271776 TI - Narrativity and non-Narrativity. AB - I argue against two popular claims. The first is a descriptive, empirical claim about the nature of ordinary human experience which I call the psychological Narrativity thesis (PNT). According to PNT, 'each of us constructs and lives a "narrative" ... this narrative is us, our identities' (Sacks O. The Man Who Mistook His Wife for a Hat. London: Duckworth; 1985, 110). The second is a normative, ethical claim which I call the ethical Narrativity thesis (ENT). According to ENT, we ought to live our lives narratively, or as a story: a 'basic condition of making sense of ourselves is that we grasp our lives in a narrative' and have an understanding of our lives 'as an unfolding story' (Taylor C. Sources of the Self. Cambridge: Cambridge University Press; 1989, 47-52). On this view a person 'creates his identity (only) by forming an autobiographical narrative-a story of his life', and must be in possession of a full and 'explicit narrative (of his life) to develop fully as a person' (Schechtman M. The Constitution of Selves. Ithaca, NY: Cornell University Press; 1996, 93. WIREs Cogn Sci 2010 1 775 780 For further resources related to this article, please visit the WIREs website. PMID- 26271775 TI - Turoctocog alfa (recombinant factor VIII). Manufacturing, characteristics and clinical trial results. AB - Turoctocog alfa (NovoEight(r)) is a new recombinant factor VIII (rFVIII) with a truncated B domain and a high degree of tyrosine sulphation, similar to plasma derived FVIII products. The manufacturing process includes double nanofiltration with a 20-nm pore size and immunoaffinity chromatography with monoclonal F25 anti FVIII antibodies. Treatment with turoctocog alfa can be monitored with both one stage and chromogenic substrate assays without a product-specific laboratory standard. In total, 213 previously-treated patients with severe haemophilia A participated in the pivotal part of the clinical trial programme guardianTM. The median annualised bleeding rate during turoctocog alfa prophylaxis was 3.7 and 3.0 in adolescents/adults and children, respectively, with marked differences between participating countries. The success rate for the treatment of breakthrough bleeds was 85% (adults/adolescents) and 94% (children). A total of 41 surgical procedures (15 major, 26 minor) were performed in 33 patients, with a successful haemostatic response reported in all cases. No patient developed confirmed inhibitors in any of the trials. PMID- 26271777 TI - Visual hallucinations. AB - Understanding of visual hallucinations is developing rapidly. Single-factor explanations based on specific pathologies have given way to complex multifactor models with wide potential applicability. Clinical studies of disorders with frequent hallucinations-dementia, delirium, eye disease and psychosis-show that dysfunction within many parts of the distributed ventral object perception system is associated with a range of perceptions from simple flashes and dots to complex formed figures and landscapes. Dissociations between these simple and complex hallucinations indicate at least two hallucinatory syndromes, though exact boundaries need clarification. Neural models of hallucinations variably emphasize the importance of constraints from top down dorsolateral frontal systems, bottom up occipital systems, interconnecting tracts, and thalamic and brainstem regulatory systems. No model has yet gained general acceptance. Both qualitative (a small number of necessary and sufficient constraints) and quantitative explanations (an accumulation of many nonspecific factors) fit existing data. Variable associations of hallucinations with emotional distress and thought disorders across and within pathologies may reflect the roles of cognitive and regulatory systems outside of the purely perceptual. Functional imaging demonstrates that hallucinations and veridical perceptions occur in the same brain areas, intimating a key role for the negotiating interface between top down and bottom up processes. Thus, hallucinations occur when a perception that incorporates a hallucinatory element can provide a better match between predicted and actual sensory input than does a purely veridical experience. Translational research that integrates understandings from clinical hallucinations and basic vision science is likely to be the key to better treatments. WIREs Cogn Sci 2010 1 781-786 For further resources related to this article, please visit the WIREs website. PMID- 26271778 TI - Perception and action. AB - The phrase perception and action is used widely but in diverse ways in the context of the relationship between perceptual and motor processes. This review describes and integrates five perspectives on perception and action which rely on both neurophysiological and behavioral levels of analysis. The two visual systems view proposes dissociable but interactive systems for conscious processing of objects/space and the visual control of action. The integrative view proposes tightly calibrated but flexible systems for perception and motor control in spatial representation. The embodied view posits that action underlies perception, involving common coding or motor simulation systems, and examines the relationship between action observation, imitation, and the understanding of intention. The ecological view emphasizes environmental information and affordances in perception. The functional view defines the relationship between perception, action planning, and semantics in goal-directed actions. Although some of these views/approaches differ in significant ways, their shared emphasis on the importance of action in perception serves as a useful unifying framework. WIREs Cogn Sci 2010 1 800-810 For further resources related to this article, please visit the WIREs website. PMID- 26271779 TI - Bayesian models of cognition. AB - There has been a recent explosion in research applying Bayesian models to cognitive phenomena. This development has resulted from the realization that across a wide variety of tasks the fundamental problem the cognitive system confronts is coping with uncertainty. From visual scene recognition to on-line language comprehension, from categorizing stimuli to determining to what degree an argument is convincing, people must deal with the incompleteness of the information they possess to perform these tasks, many of which have important survival-related consequences. This paper provides a review of Bayesian models of cognition, dividing them up by the different aspects of cognition to which they have been applied. The paper begins with a brief review of Bayesian inference. This falls short of a full technical introduction but the reader is referred to the relevant literature for further details. There follows reviews of Bayesian models in Perception, Categorization, Learning and Causality, Language Processing, Inductive Reasoning, Deductive Reasoning, and Argumentation. In all these areas, it is argued that sophisticated Bayesian models are enhancing our understanding of the underlying cognitive computations involved. It is concluded that a major challenge is to extend the evidential basis for these models, especially to accounts of higher level cognition. WIREs Cogn Sci 2010 1 811-823 For further resources related to this article, please visit the WIREs website. PMID- 26271780 TI - Robot soccer. AB - Robot soccer is a test bed for a variety of robotic and Artificial Intelligence (AI) methods. Its relevance to Cognitive Science is that it confronts the designer with a task that requires the integration of almost all aspects of AI to create an agent that is capable of working in a complex, dynamic environment inhabited by other agents, some of which are cooperative and others competitive. We describe the main elements that make up a robot soccer player and how these players associate to create effective teams. We pay special attention to the architecture of the players. WIREs Cogn Sci 2010 1 824-833 For further resources related to this article, please visit the WIREs website. PMID- 26271781 TI - Language production. AB - Linguistic expressions are produced through a multicomponent multistage process. This article describes the major components of the language-production process and discusses issues of current research focus. General mechanisms of word and sentence production are described. This is followed by discussion of language production in conversation, different modes of production (written production, sign language, monitoring, bilingualism, aphasia, corpus research), and the relationship of language-production mechanisms to other cognitive systems (eye movements, attention, memory, gesture), before ending with concluding thoughts. WIREs Cogn Sci 2010 1 834-844 For further resources related to this article, please visit the WIREs website. PMID- 26271782 TI - Models of processing: discourse. AB - This article discusses models of discourse processing, primarily from a psycholinguistic perspective, though considerations from the other cognitive sciences are mentioned where appropriate. It also touches on issues of discourse representation, because questions about representation and questions about process are closely intertwined. The origins of an interest in questions about discourse are identified in Bransford's ideas from the early 1970s. Their development into more detailed models of discourse processing is discussed, and detailed descriptions are given of, in particular, anaphor processing and, to a lesser extent the establishment of coherence. Some issues that arise in connection with the production of discourse are briefly discussed, as are their relation to dialog rather than to monolog. WIREs Cogn Sci 2010 1 845-853 For further resources related to this article, please visit the WIREs website. PMID- 26271783 TI - Stimulus-driven capture and contingent capture. AB - Whether or not certain physical events can capture attention has been one of the most debated issues in the study of attention. This discussion is concerned with how goal-directed and stimulus-driven processes interact in perception and cognition. On one extreme of the spectrum is the idea that attention capture is primarily stimulus driven and automatic. On the other end is the notion that attention capture is always contingent on the goals of the observer, and thus under top-down control. This review discusses the empirical evidence for each of these viewpoints and the theoretical consequences. In addition, there is a discussion of the issues that remain controversial within the debate between the two viewpoints. It is concluded that visual selection depends on the interaction between bottom-up and top-down processes with a special role for spatial attention as the top-down gatekeeper for attention capture. WIREs Cogn Sci 2010 1 872-881 For further resources related to this article, please visit the WIREs website. PMID- 26271785 TI - Infant categorization. AB - In this article, we review the principal findings on infant categorization from the last 30 years. The review focuses on behaviorally based experiments with visual preference, habituation, object examining, sequential touching, and inductive generalization procedures. We propose that although this research has helped to elucidate the 'what' and 'when' of infant categorization, it has failed to clarify the mechanisms that underpin this behavior and the development of concepts. We outline a number of reasons for why the field has failed in this regard, most notably because of the context-specific nature of infant categorization and a lack of ground rules in interpreting data. We conclude by suggesting that one remedy for this issue is for infant categorization researchers to adopt more of an interdisciplinary approach by incorporating imaging and computational methods into their current methodological arsenal. WIREs Cogn Sci 2010 1 894-905 For further resources related to this article, please visit the WIREs website. PMID- 26271784 TI - Animal cognition. AB - The main topics in the study of animal cognition are reviewed with special reference to direct links to human, and in particular developmental, cognitive sciences. The material is organized with regard to the general idea that biological organisms would be endowed with a small set of separable systems of core knowledge, a prominent hypothesis in the current developmental cognitive sciences. Core knowledge systems would serve to represent inanimate physical objects and their mechanical interactions (natural physics); numbers with their relationships of ordering, addition, and subtraction (natural mathematics); places in the spatial layout with their geometric relationships (natural geometry); and animate psychological objects (agents) with their goal-directed actions (natural psychology). Some advanced forms of animal cognition, such as episodic-like representations and planning for the future, are also discussed. WIREs Cogn Sci 2010 1 882-893 For further resources related to this article, please visit the WIREs website. PMID- 26271786 TI - Mental time travel in animals. PMID- 26271787 TI - Development of Genome-Wide Insertion and Deletion Polymorphism Markers from Next Generation Sequencing Data in Rice. AB - BACKGROUND: Next-generation sequencing technologies enable the re-sequencing of a large number of genomes and provide an unprecedented opportunity to discover numerous DNA polymorphisms throughout the genome of a species. As the second most abundant form of genetic variation, InDels, with characteristics of co-dominance, multiple alleles and high stability and density and that are easy to genotype, have received an increasing amount attention. RESULTS: In this work, a total of 2,329,544 InDels were identified in 1767 rice genomes; these InDels were dispersed across all 12 rice chromosomes, with one InDel marker found, on average, every 160.22 bp. There were 162,380 highly polymorphic InDels with a polymorphism information content (PIC) >= 0.5, contributing 1.81 % to the unique primer set. Of these highly polymorphic InDels, we also selected InDels with major allele differences (the size difference between the most and second most frequent alleles) >= 3 bp or 8 bp for primer design, which provided a more flexible choice for researchers. Finally, we experimentally validated 100 highly polymorphic InDels for accuracy and polymorphism. The PCR results showed that the accuracy of the InDel markers was 95.70 %, while the average PIC value was 0.56, with a range of 0.19 to 0.78; the average allele number was 3.02, with a range of 2 to 5. CONCLUSIONS: Our genome-wide and easily used InDel markers with high polymorphism and density in both cultivated and wild rice will undoubtedly have practical implications in rice marker-assisted breeding and will also meet the need of fine-scale genetic mapping in map-based rice gene cloning. PMID- 26271788 TI - Drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome: clinical features of 27 patients. AB - BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) [also called drug-induced hypersensitivity syndrome (DIHS)] includes severe reactions to drugs that need to be promptly recognized by physicians. AIM: To explore heterogeneity in the clinical presentation of DRESS/DIHS at a large academic hospital in Latin America, using the criteria defined by the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) scoring system. METHODS: A retrospective medical record review of 60 patients with diagnostic suspicion of DRESS/DIHS admitted to our hospital between July 2008 and April 2012 was performed, including demographic data, clinical features, laboratory findings and treatment. RESULTS: Of the 60 patients, 27 fulfilled the criteria for DRESS/DIHS. Maculopapular exanthema (85.1%), fever (96.2%) and hepatic involvement (85.1%) were the most common features. Anticonvulsants were the most common causal drugs (77.7%); Phenytoin was the most common individual drug (44.4%), followed by carbamazepine (29.6%). All patients were treated initially with prednisone 1 mg/kg/day. Mortality rate was 4%. CONCLUSION: The major findings of this study (to our knowledge the largest collection of data on DRESS/DIHS in Latin America) include a positive statistical association between presence of atypical lymphocytes and higher levels of alanine aminotransferase (P < 0.001) and reinforce the importance of anticonvulsants in the pathogenesis of this severe reaction. PMID- 26271789 TI - Advances in Radiation Therapy in Pediatric Neuro-oncology. AB - Radiation therapy remains a highly effective therapy for many pediatric central nervous system tumors. With more children achieving long-term survival after treatment for brain tumors, late-effects of radiation have become an important concern. In response to this problem, treatment protocols for a variety of pediatric central nervous system tumors have evolved to reduce radiation fields and doses when possible. Recent advances in radiation technology such as image guidance and proton therapy have led to a new era of precision treatment with significantly less exposure to healthy tissues. These developments along with the promise of molecular classification of tumors and targeted therapies point to an optimistic future for pediatric neuro-oncology. PMID- 26271790 TI - Pilot Testing Behavior Therapy for Chronic Tic Disorders in Neurology and Developmental Pediatrics Clinics. AB - Comprehensive Behavioral Intervention for Tics (CBIT) is an efficacious treatment with limited regional availability. As neurology and pediatric clinics are often the first point of therapeutic contact for individuals with tics, the present study assessed preliminary treatment response, acceptability, and feasibility of an abbreviated version, modified for child neurology and developmental pediatrics clinics. Fourteen youth (9-17) with Tourette disorder across 2 child neurology clinics and one developmental pediatrics clinic participated in a small case series. Clinician-rated tic severity (Yale Global Tic Severity Scale) decreased from pre- to posttreatment, z = -2.0, P < .05, r = -.48, as did tic-related impairment, z = -2.4, P < .05, r = -.57. Five of the 9 completers (56%) were classified as treatment responders. Satisfaction ratings were high, and therapeutic alliance ratings were moderately high. Results provide guidance for refinement of this modified CBIT protocol. PMID- 26271791 TI - Persistence of Cerebral Palsy Diagnosis: Assessment of a Low-Birth-Weight Cohort at Ages 2, 6, and 9 Years. AB - We examined the stability of nondisabling and disabling cerebral palsy at age 2 in a longitudinally followed tri-county low-birth-weight (<2000 g) birth cohort. A total of 1105 newborns were enrolled, 901 (81.5%) survived to age 2, and 86% (n = 777) were followed up. Of the 113 cerebral palsy diagnoses at age 2, 61 (9% of the cohort, n = 61/777) had disabling cerebral palsy and 52 (7%, n = 52/777) had nondisabling cerebral palsy. Of 48 followed children diagnosed with disabling cerebral palsy at age 2, 98% were again classified as having cerebral palsy at school age, and 1 had an uncertain cerebral palsy status. By contrast, 41% (n = 17) of the 43 children diagnosed with nondisabling cerebral palsy at age 2 were classified as not having cerebral palsy. Of the 517 followed children who were not diagnosed with cerebral palsy at age 2, 7% (n = 35) were classified as having late emerging nondisabling cerebral palsy at school age. PMID- 26271792 TI - Prevalence and Clinical Characteristics of Headaches in PHACE Syndrome. AB - PHACE (posterior fossa brain malformation, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities) syndrome is a neurocutaneous disorder often involving the cerebral vasculature. PHACE patients appear to have early-onset and severe headaches more commonly than children without PHACE. The objective of this study was to characterize the clinical features and prevalence of headache by conducting a cross-sectional survey of families in 2 large PHACE registries. Sixty-six percent of eligible families completed the survey in which 62.7% of respondents reported headaches. Average age of headache onset was 48.8 months. Females were more likely to have headaches (68.6% vs 30.8%, P = .014). Families reported associated migrainous features including nausea (62.5%), vomiting (37.5%), photophobia (75%), and phonophobia (75%). Headaches occurred at least weekly in 29.4%, lasted >=1 hour in 85.4%, and led to >=1 hospital admission in 15.7%. Three respondents with headaches had at least 1 ischemic stroke. We demonstrated that headaches are common among PHACE patients, develop at an early age, and have migrainous features. PMID- 26271793 TI - Diagnostic Approach to Genetic Causes of Early-Onset Epileptic Encephalopathy. AB - Epileptic encephalopathies are characterized by recurrent clinical seizures and prominent interictal epileptiform discharges seen during the early infantile period. Although epileptic encephalopathies are mostly associated with structural brain defects and inherited metabolic disorders, pathogenic gene mutations may also be involved in the development of epileptic encephalopathies even when no clear genetic inheritance patterns or consanguinity exist. The most common epileptic encephalopathies are Ohtahara syndrome, early myoclonic encephalopathy, epilepsy of infancy with migrating focal seizures, West syndrome and Dravet syndrome, which are usually unresponsive to traditional antiepileptic medication. Many of the diagnoses describe the phenotype of these electroclinical syndromes, but not the underlying causes. To date, approximately 265 genes have been defined in epilepsy and several genes including STXBP1, ARX, SLC25A22, KCNQ2, CDKL5, SCN1A, and PCDH19 have been found to be associated with early-onset epileptic encephalopathies. In this review, we aimed to present a diagnostic approach to primary genetic causes of early-onset epileptic encephalopathies. PMID- 26271794 TI - Combination of external beam radiotherapy and Californium (Cf)-252 neutron intracavity brachytherapy is more effective in control of cervical squamous cell carcinoma than that of cervical adenocarcinoma. AB - The objective of this study was to compare the effect of combined external beam radiotherapy (EBRT) and Californium (Cf)-252 neutron intracavity brachytherapy (ICBT) on cervical squamous versus adenocarcinoma. A total of 106 patients with stage IB-IIIB cervical cancer were accrued between January 2005 and May 2011 and divided into squamous cell carcinoma (SCC) and adenocarcinoma (AC) as a pair with 53 patients in each group according to tumor size, stage, age, and hemoglobin level using matched-pair design. The whole pelvic EBRT was performed with 2 Gy/fraction, 4 fractions/week. The total dose was 48-54 Gy (the center of whole pelvic field was blocked by 4 cm in width after 20-36 Gy). Cf-252 neutron ICBT was delivered with 11 and 12 Gy-eq/f with the total dose at point A of 44 and 48 Gy-eq for SCC and AC patients, respectively. The mean follow-up time was 43 months. The 5-year LC, OS, DFS, LAC rates, and mean survival time were 66.0, 56.6, 52.8.0, 17.0%, and 76.4 +/- 6.2 months, respectively, for AC patients, whereas they were 81.1, 69.8, 67.9, 11.3%, and 93.3 +/- 4.3 months, respectively, for SCC patients. Furthermore, the early treatment toxicity was mild in both groups, the late treatment complications were mainly radiation-induced proctitis and cystitis, and there were no grade 3 or higher complications. Although the combination of Cf-252 neutron ICBT and EBRT was effective in both histology types of cervical cancer, a more aggressive strategy is needed to control cervical AC. PMID- 26271795 TI - Comparison Review of Short-Acting and Long-Acting Glucagon-like Peptide-1 Receptor Agonists. AB - Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) are useful tools for treating type 2 diabetes mellitus. In their recent position statement, the American Diabetes Association and European Association for the Study of Diabetes recommend GLP1-RAs as add-on to metformin when therapeutic goals are not achieved with monotherapy, particularly for patients who wish to avoid weight gain or hypoglycemia. GLP1-RAs differ substantially in their duration of action, frequency of administration and clinical profile. Members of this class approved for clinical use include exenatide twice-daily, exenatide once-weekly, liraglutide and lixisenatide once-daily. Recently, two new once-weekly GLP1-RAs have been approved: dulaglutide and albiglutide. This article summarizes properties of short- and long-acting GLP-1 analogs, and provides useful information to help choose the most appropriate compound for individual patients. PMID- 26271797 TI - Effects of learning content in context on knowledge acquisition and recall: a pretest-posttest control group design. AB - BACKGROUND: It is generally assumed that learning in context increases performance. This study investigates the relationship between the characteristics of a paper-patient context (relevance and familiarity), the mechanisms through which the cognitive dimension of context could improve learning (activation of prior knowledge, elaboration and increasing retrieval cues), and test performance. METHODS: A total of 145 medical students completed a pretest of 40 questions, of which half were with a patient vignette. One week later, they studied musculoskeletal anatomy in the dissection room without a paper-patient context (control group) or with (ir)relevant-(un)familiar context (experimental groups), and completed a cognitive load scale. Following a short delay, the students completed a posttest. RESULTS: Surprisingly, our results show that students who studied in context did not perform better than students who studied without context. This finding may be explained by an interaction of the participants' expertise level, the nature of anatomical knowledge and students' approaches to learning. A relevant-familiar context only reduced the negative effect of learning the content in context. Our results suggest discouraging the introduction of an uncommon disease to illustrate a basic science concept. Higher self-perceived learning scores predict higher performance. Interestingly, students performed significantly better on the questions with context in both tests, possibly due to a 'framing effect'. CONCLUSIONS: Since studies focusing on the physical and affective dimensions of context have also failed to find a positive influence of learning in a clinically relevant context, further research seems necessary to refine our theories around the role of context in learning. PMID- 26271796 TI - Validation of the New Interpretation of Gerasimov's Nasal Projection Method for Forensic Facial Approximation Using CT Data(.). AB - The most common method to predict nasal projection for forensic facial approximation is Gerasimov's two-tangent method. Ullrich H, Stephan CN (J Forensic Sci, 2011; 56: 470) argued that the method has not being properly implemented and a revised interpretation was proposed. The aim of this study was to compare the accuracy of both versions using a sample of 66 postmortem cranial CT data. The true nasal tip was defined using pronasale and nasal spine line, as it was not originally specified by Gerasimov. The original guidelines were found to be highly inaccurate with the position of the nasal tip being overestimated by c. 2 cm. Despite the revised interpretation consistently resulting in smaller distance from true nasal tip, the method was not statistically accurate (p > 0.05) in positioning the tip of the nose (absolute distance >5 mm). These results support that Gerasimov's method was not properly performed, and Ullrich H, Stephan CN (J Forensic Sci, 2011; 56: 470) interpretation should be used instead. PMID- 26271798 TI - Relative biological effectiveness of carbon ions for tumor control, acute skin damage and late radiation-induced fibrosis in a mouse model. AB - BACKGROUND: The aim of the present study was to compare the biological effectiveness of carbon ions relative to x-rays between tumor control, acute skin reaction and late RIF of CDF1 mice. MATERIAL AND METHODS: CDF1 mice with a C3H mouse mammary carcinoma implanted subcutaneously on the foot of the right hind limb were irradiated with single fractions of either photons, or (12)C ions using a 30-mm spread-out Bragg peak. The endpoint of the study was local control (no tumor recurrence within 90 days). For the acute skin reaction, non-tumor bearing CDF1 mice were irradiated with a comparable radiation scheme, and monitored for acute skin damage between Day 7 and 40. Late RIF was assessed in the irradiated mice. RESULTS: The TCD50 (dose producing tumor control in 50% of mice) values with 95% confidence interval were 29.7 (25.4-34.8) Gy for C ions and 43.9 (39.2 49.2) Gy for photons, with a corresponding Relative biological effectiveness (RBE) value of 1.48 (1.28-1.72). For acute skin damage the MDD50 (dose to produce moist desquamation in 50% of mice) values with 95% confidence interval were 26.3 (23.0-30.1) Gy for C ions and 35.8 (32.9-39.0) Gy for photons, resulting in a RBE of 1.36 (1.20-1.54). For late radiation-induced fibrosis the FD50 (dose to produce severe fibrosis in 50% of mice) values with 95% confidence interval were 26.5 (23.1-30.3) Gy for carbon ions and 39.8 (37.8-41.8) Gy for photons, with a RBE of 1.50 (1.33-1.69). CONCLUSION: The observed RBE values were very similar for tumor response, acute skin damage and late RIF when irradiated with large doses of high- linear energy transfer (LET) carbon ions. This study adds information to the variation in biological effectiveness in different tumor and normal tissue models. PMID- 26271800 TI - Prognostic factors for the feasibility of chemotherapy and the Geriatric Prognostic Index (GPI) as risk profile for mortality before chemotherapy in the elderly. AB - BACKGROUND: Comprehensive geriatric assessment (CGA) is a multidimensional method to detect frailty in elderly patients. Time saving could be accomplished by identifying those individual items that classify elderly cancer patients at risk for feasibility of chemotherapy and for mortality. MATERIAL AND METHODS: Patients older than 70 years of age were assessed before the first chemotherapy administration. GA consisted of the Mini Nutritional Assessment (MNA), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Groningen Frailty Indicator (GFI) and Mini Mental State Examination (MMSE). Predictive individual items for feasibility of chemotherapy and mortality were entered in the multivariable logistic regression and Cox-regression models, and a three-item sum scale was constructed: the Geriatric Prognostic Index (GPI). RESULTS: The 494 patients had a median age of 75 years (range 70-92 years). The majority of the patients had malignancies of the digestive tract (41.7%) followed by hematological tumors (22.3%). Three items of the MNA ('psychological distress or acute disease in the past three months', 'neuropsychological problems' and 'using > 3 prescript drugs') independently predicted for feasibility of chemotherapy. Two items of the MNA and one of the GFI ('declining food intake in past 3 months', 'using > 3 prescript drugs', and 'dependence in shopping') independently predicted for mortality. In comparison with patients without any positive item on the three-item GPI, patients with one, two or three positive items had hazard ratios (HRs) of 1.58, 2.32, and 5.58, respectively (all p < 0.001). CONCLUSIONS: With only three items of the MNA, feasibility of chemotherapy can be predicted. The three-item GPI may help to identify elderly cancer patients at elevated risk for mortality. PMID- 26271799 TI - Impact of radiation dose and standardized uptake value of (18)FDG PET on nodal control in locally advanced cervical cancer. AB - BACKGROUND: Despite local control now exceeding 90% with image-guided adaptive brachytherapy (IGABT), regional and distant metastases continue to curb survival in locally advanced cervical cancer. As regional lymph nodes often represent first site of metastatic spread, improved nodal control could improve survival. The aim of this study was to examine optimal volume and dose of external beam radiotherapy (EBRT) to maximize regional control including dose contribution from IGABT. MATERIAL AND METHODS: In total 139 patients from the EMBRACE study were analyzed. Individual nodal dose was determined by dose-maps from EBRT and IGABT. All PET/CT scans were re-evaluated and nodal maximal standard uptake value (SUVmax) was determined. Nodal failures were registered to planning scans and related to boosted nodes and treated volume. Relation between SUVmax and nodal control as well as the pattern of regional nodal failure were analyzed. RESULTS: Eighty-four patients were node positive. Nine patients had all metastatic nodes surgically removed. Seventy-five patients had 209 nodes boosted with EBRT. Median nodal boost dose was 62 Gy EQD2 (53-69 Gy EQD2). Median SUVmax was 6 (2-22). No patients had persistent nodal disease, but six patients recurred in a boosted node. SUVmax was significantly higher in nodes that recurred (p = 0.02). However, there was no correlation to nodal dose or volume. Twenty-one patients had a nodal failure including para-aortic nodal (PAN) metastases above the irradiated volume. Nine patients had a PAN-only failure. Patients receiving <= 4 cycles of weekly cisplatin had higher risk of nodal failure (p < 0.01). CONCLUSION: Current RT practice provides a high level of control in both boosted nodes and the elective irradiated regional target. However, a high nodal SUVmax is a negative prognostic predictor for nodal control. Attention should be raised to administration of a complete schedule of concurrent chemotherapy as well as treatment of para-aortic nodes. PMID- 26271801 TI - SPECT/CT Assessment of Infected Intracardiac Devices With and Without Attenuation Correction. AB - Left ventricular assist devices (LVADs) provide the ability to maintain cardiac output and sustain life as a bridge to transplantation, definitive therapy, or a permanent decision. We present a case of LVAD drive infection that was differentiated from pump infection by the use of attenuation-corrected and non attenuation-corrected CT, along with correlation with the planar images. Clinically, the patient was suspected of having infection; however, the clinician did not know which components of the device were involved. The patient's scan showed abnormal activity along the driveline with and without attenuation correction, whereas the pump showed abnormal activity with attenuation correction only. This finding suggested that the drive line was infected but that the activity within the pump was secondary to overcorrection of attenuation. The driveline was cultured, confirming infection. PMID- 26271802 TI - Influence of Statistical Fluctuation on Reproducibility and Accuracy of SUVmax and SUVpeak: A Phantom Study. AB - Standardized uptake values (SUVs) have been widely used in the diagnosis of malignant tumors and in clinical trials of tumor therapies as semiquantitative metrics of tumor (18)F-FDG uptake. However, SUVs for small lesions are liable to errors due to partial-volume effect and statistical noise. The purpose of this study was to evaluate the reproducibility and accuracy of maximum and peak SUV (SUVmax and SUVpeak, respectively) of small lesions in phantom experiments. METHODS: We used a body phantom with 6 spheres in a quarter warm background. The PET data were acquired for 1,800 s in list-mode, from which data were extracted to generate 15 PET images for each of the 60-, 90-, 120-, 150-, and 180-s scanning times. The SUVmax and SUVpeak of the hot spheres in the 1,800-s scan were used as a reference (SUVref,max and SUVref,peak). Coefficients of variation for both SUVmax and SUVpeak in hot spheres (CVmax and CVpeak) were calculated to evaluate the variability of the SUVs. On the other hand, percentage differences between SUVmax and SUVref,max and between SUVpeak and SUVref,peak were calculated for evaluation of the accuracy of SUV. We additionally examined the coefficients of variation of background activity and the percentage background variability as parameters for the physical assessment of image quality. RESULTS: Visibility of a 10-mm-diameter hot sphere was considerably different among scan frames. The CVmax and CVpeak increased as the sphere size became smaller and as the acquisition time became shorter. SUVmax was generally overestimated as the scan time shortened and the sphere size increased. The SUVmax and SUVpeak of a 37-mm diameter sphere for 60-s scans had average positive biases of 28.3% and 4.4%, compared with the reference. CONCLUSION: SUVmax was variable and overestimated as the scan time decreased and the sphere size increased. In contrast, SUVpeak was a more robust and accurate metric than SUVmax. The measurements of SUVpeak (or SUVpeak normalized to lean body mass) in addition to SUVmax are desirable for reproducible and accurate quantification in clinical situations. PMID- 26271803 TI - Tailoring 99mTc-Macroaggregated Albumin Administration to Optimize Patient Dose Reduction. AB - In the ever-changing field of nuclear medicine, best-practice considerations cannot simply go unchallenged for months and years, with the need to minimize radiation exposure to patients highlighted in "as low as reasonably achievable" principles. The Australian Radiation Protection and Nuclear Safety Agency reports that the dose for (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) administered should be 180-200 MBq. An objective of imaging in pulmonary embolism, or indeed any diagnostic procedure involving radiation, is to minimize radiation exposure without sacrificing image quality and diagnostic accuracy. The amount of radiation involved must be considered together with imaging protocols. Our aim was to reduce the amount of (99m)Tc-MAA administered without compromising the diagnostic quality of the scan. METHODS: To achieve a ventilation-to-perfusion ratio of 1:4, we ventilated the patient as per standard protocol and then placed intravenous access into the patient. For the perfusion component, 180-200 MBq were prepared in a 2-mL injection. Aliquots of 0.5 mL of (99m)Tc-MAA were administered every 30 s followed by a 5-mL saline flush until the required ventilation-to-perfusion ratio was achieved. RESULTS: With this protocol, the average administered dose was 105 +/- 20.7 MBq (vs. 180 +/- 5.3 MBq, P < 0.0001). CONCLUSION: By individually tailoring the administered dose, diagnostic quality is maintained while achieving a significant dose reduction. PMID- 26271804 TI - Diagnosis of Dual Malignancy by 18F-FDG PET/CT in the Setting of Paraneoplastic Cerebellar Degeneration. AB - We describe a rare case of paraneoplastic cerebellar degeneration (with detectable antineuronal antibody anti-Yo) in which (18)F-FDG PET/CT aided in the detection of 2 synchronous malignancies (one thyroid cancer and the other breast cancer). Interestingly, the primary breast malignancy was non-(18)F-FDG-avid and was detected through the presence of a metastatic (18)F-FDG-avid axillary lymph node. Surgery for both was undertaken in the same sitting, and there was improvement of the neurologic features soon after the surgical removal of the malignancies. PMID- 26271805 TI - The Evaluation of Cardiac Sarcoidosis with 18F-FDG PET. AB - Cardiac involvement in sarcoidosis is associated with poor prognosis. (18)F-FDG PET can detect the presence of cardiac sarcoidosis, assess disease activity, and serve as a means to monitor treatment response in patients with cardiac sarcoidosis. PMID- 26271806 TI - Technical Considerations in Brain Amyloid PET Imaging with 18F-Florbetapir. AB - Technical factors play a critical role in the production of best-quality amyloid PET images for interpretation. This article provides specific instructions and general technical information about PET brain scanning of beta-amyloid neuritic plaques. The focus of tracer-specific information will be on (18)F-florbetapir (indications, contraindications, dosing, administration, uptake time, scanning time, acquisition, processing, biodistribution, radiation dose, adverse events, and display). General scanning information relevant to all amyloid-imaging agents will be also be presented (e.g., mechanism of uptake, safe handling, positioning, prevention of patient motion, processing, and artifacts). PMID- 26271807 TI - The Relationship Between Problem Gambling and Attention Deficit Hyperactivity Disorder. AB - Recent studies indicate that treatment-seeking problem gamblers display elevated rates of ADHD and that adolescents who screen positive for ADHD are more likely to engage in gambling, develop gambling problems, and experience a greater severity in gambling problems. This study aimed to (a) compare the prevalence of ADHD in treatment-seeking problem gamblers to the general population; (b) investigate the relationships between ADHD and problem gambling severity, cluster B personality disorders, motor impulsivity, alcohol use, substance use, gender, and age; and (c) investigate the degree to which these factors moderate the relationship between ADHD and problem gambling severity. Participants included 214 adults (154 males, 58 females, 2 unspecified) who sought treatment for their gambling problems at a specialist gambling agency in Melbourne, Australia. Almost one-quarter (24.9 %) of treatment-seeking problem gamblers screened positively for ADHD, which was significantly higher than the 14 % prevalence in a community sample. ADHD was significantly positively correlated with problem gambling severity, motor impulsivity, and cluster B personality disorders, but was not associated with alcohol and substance use, gender or age. None of the factors significantly moderated the relationship between ADHD and problem gambling severity. These findings suggest that a considerable proportion of treatment seeking problem gamblers report ADHD and that their clinical profile is complicated by the presence of high impulsivity and cluster B personality disorders. They highlight the need for specialist gambling agencies to develop screening, assessment, and management protocols for co-occurring ADHD to enhance the effectiveness of treatment. PMID- 26271808 TI - Genome mining of fungal lipid-degrading enzymes for industrial applications. AB - Lipases are interesting enzymes, which contribute important roles in maintaining lipid homeostasis and cellular metabolisms. Using available genome data, seven lipase families of oleaginous and non-oleaginous yeast and fungi were categorized based on the similarity of their amino acid sequences and conserved structural domains. Of them, triacylglycerol lipase (patatin-domain-containing protein) and steryl ester hydrolase (abhydro_lipase-domain-containing protein) families were ubiquitous enzymes found in all species studied. The two essential lipases rendered signature characteristics of integral membrane proteins that might be targeted to lipid monolayer particles. At least one of the extracellular lipase families existed in each species of yeast and fungi. We found that the diversity of lipase families and the number of genes in individual families of oleaginous strains were greater than those identified in non-oleaginous species, which might play a role in nutrient acquisition from surrounding hydrophobic substrates and attribute to their obese phenotype. The gene/enzyme catalogue and relevant informative data of the lipases provided by this study are not only valuable toolboxes for investigation of the biological role of these lipases, but also convey potential in various industrial applications. PMID- 26271809 TI - The extracellular matrix protein matrilin-2 induces post-burn inflammatory responses as an endogenous danger signal. AB - OBJECTIVE AND DESIGN: This prospective experimental study aims to investigate whether matrilin-2 is released from burn injury and induces post-burn inflammatory responses as an endogenous danger signal. SUBJECTS: Fifteen burn patients, 15 volunteers, 12 matrilin-2-deficient mice, 36 C57BL/6 mice and raw 264.7 cells. METHODS: Matrilin-2 levels were detected by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction. The inflammatory cytokines production in Matn2 deficient mice and wide type mice were detected by ELISA. Macrophages were activated by recombinant mouse MATN2 with or without adding anti-Toll-like receptor (TLR) 4 antibody. Student's t test and one way analysis of variance were used for statistical analysis. RESULTS: The matrilin-2 levels in serum of burned patients were drastically elevated as compared to those of healthy controls. The matrilin-2 levels in burned mice were significantly increased than those of non-burned controls, whereas the matrilin-2 mRNA expression was not significantly changed after burn. In addition, Matn2 deficient mice showed remarkably less inflammatory cytokines production and less neutrophil infiltration in lung. Exogenous MATN2 induced potent expression of proinflammatory cytokines production in macrophages, which was inhibited by anti TLR4 antibody. CONCLUSION: Matrilin-2 induces post-burn inflammatory responses as an endogenous danger signal, partly through a TLR4-mediated mechanism. PMID- 26271811 TI - Lymphoproliferative associated type 1 cryoglobulinemia. PMID- 26271812 TI - Mechanoresponsive nanotherapeutic for localized drug delivery to flow obstructed blood vessels. PMID- 26271810 TI - Drosophila Shep and C. elegans SUP-26 are RNA-binding proteins that play diverse roles in nervous system development. AB - The Caenorhabditis elegans gene sup-26 encodes a well-conserved RNA-recognition motif-containing RNA-binding protein (RBP) that functions in dendrite morphogenesis of the PVD sensory neuron. The Drosophila ortholog of sup-26, alan shepard (shep), is expressed throughout the nervous system and has been shown to regulate neuronal remodeling during metamorphosis. Here, we extend these studies to show that sup-26 and shep are required for the development of diverse cell types within the nematode and fly nervous systems during embryonic and larval stages. We ascribe roles for sup-26 in regulating dendrite number and the expression of genes involved in mechanosensation within the nematode peripheral nervous system. We also find that in Drosophila, shep regulates dendrite length and branch order of nociceptive neurons, regulates the organization of neuronal clusters of the peripheral nervous system and the organization of axons within the ventral nerve cord. Taken together, our results suggest that shep/sup-26 orthologs play diverse roles in neural development across animal species. Moreover, we discuss potential roles for shep/sup-26 orthologs in the human nervous system. PMID- 26271813 TI - Young Men's Social Network Characteristics and Associations with Sexual Partnership Concurrency in Tanzania. AB - Social network influence on young people's sexual behavior is understudied in sub Saharan Africa. Previous research identified networks of mostly young men in Dar es Salaam who socialize in "camps". This study describes network characteristics within camps and their relationship to young men's concurrent sexual partnerships. We conducted surveys with a nearly complete census of ten camp networks (490 men and 160 women). Surveys included name generators to identify camp-based networks. Fifty seven percent of sexually active men (n = 471) reported past year concurrency, measured using the UNAIDS method. In a multivariable model, men's individual concurrency was associated with being a member of a closer knit camp in which concurrency was the normative behavior. Younger men who had older members in their networks were more likely to engage in concurrency. Respondent concurrency was also associated with inequitable personal gender norms. Our findings suggest strategies for leveraging social networks for HIV prevention among young men. PMID- 26271814 TI - High HIV Prevalence and Associated Risk Factors Among Female Sexual Partners of Male Injection Drug Users (MWID) in Ho Chi Minh City, Vietnam. AB - Injection drug use is a major factor in acquiring and transmitting HIV in Vietnam. This analysis aims to present estimates of HIV infection and factors associated with HIV infection among female sex partners (FSP) of MWID in Ho Chi Minh City (HCMC), Vietnam. Cross-sectional surveys were conducted in 2011 and 2013 among males who inject drugs (MWID) who then referred their FSP for a behavioral and biologic survey. In total, 445 MWID and FSPs were enrolled. HIV prevalence among MWID was 50 and 35 % among FSPs. Among FSPs, 60.3 % reported ever using illegal drugs and among those, 72.7 % reported ever injecting illicit drugs. Among FSP, injection drug for >1 year [adjusted Odds Ratio (aOR), 95 % CI 2.94, 1.19-7.26), p value = <0.001] and having a male partner infected with HIV [(aOR 3.35: 1.97-5.69), p value = <0.001] were associated with HIV infection. The prevalence of HIV infection is high among FSP of MWID in HCMC and is highly associated with the injection drug use behavior of the FSP. Harm-reduction intervention programs that focus on the MWID-FSP couple or directly on the FSPs are required. PMID- 26271815 TI - Effectiveness of peer support on care engagement and preventive care intervention utilization among pre-antiretroviral therapy, HIV-infected adults in Rakai, Uganda: a randomized trial. AB - 442 pre-ART, HIV-infected adults were randomized to peer support consisting of structured home visits to promote clinic attendance and preventive care intervention use or standard of care. At baseline, 62 % reported previously visiting an HIV clinic, 45 % reported taking cotrimoxazole prophylaxis, and 31 % were "care-naive" (no previous clinic visit and not on cotrimoxazole). After 1 year, intervention participants were more likely to report being in care (92 vs 84 %; PRR 1.09, p = 0.039), on cotrimoxazole (89 vs 81 %; PRR 1.10, p = 0.047), and safe water vessel adherence (23 vs 14 %; PRR 1.64, p = 0.024). The effect was observed only among care-naive participants (n = 139) with 83 % intervention versus 56 % controls reporting being in HIV care (PRR 1.47, p = 0.006), 78 versus 58 % on cotrimoxazole (PRR 1.35, p = 0.04), and 20 versus 4 % safe water vessel adherence (PRR 5.78, p = 0.017). Peer support may be an effective intervention to facilitate pre-ART care compliance in this important population. PMID- 26271816 TI - Prevalence and Risk Factors of Sleep Disturbance in a Large HIV-Infected Adult Population. AB - This cross-sectional study evaluates the prevalence and factors associated with sleep disturbances in French adult HIV-infected outpatients. Patients fullfilled a self-administered questionnaire on their health behavior, sleep attitudes (Pittsburgh sleep quality index, PSQI), quality of life and depression; 1354 patients were enrolled. Median sleeping time was 7 h. Poor sleep quality was observed in 47 % of the patients, and moderate to serious depressive symptoms in 19.7 %. Factors significantly associated with sleep disturbances were depression, male gender, active employment, living single, tobacco-smoking, duration of HIV infection, nevirapine or efavirenz-including regimen. Prevalence of poor sleepers is high in this HIV adult outpatient population. Associated factors seem poorly specific to HIV infection and more related to social and psychological status. Taking care of these disturbances may prove to be an effective health management strategy. PMID- 26271818 TI - Vagus nerve stimulation in children with drug-resistant epilepsy: age at implantation and shorter duration of epilepsy as predictors of better efficacy? AB - AIM: To study the efficacy of vagus nerve stimulation (VNS) therapy in a highly drug-resistant childhood epilepsy patient group and to investigate the effect of age at implantation on efficacy. METHODS: The efficacy of VNS treatment was analysed in a cohort of 70 patients with drug-resistant epilepsy. Both children with focal (n=16) and generalized epilepsies (n=54) were included. Age at implantation varied between 19 months and 25 years. RESULTS: Overall, responder rate was 54% with 5.7% children becoming seizure-free. The only factor in our analysis that could predict good outcome was age at implantation. In the youngest group (<5 years), the responder rate was 77% and this group also included three of the four seizure-free children. These three seizure-free children were known to have tuberous sclerosis. There were no outcome differences between generalized and focal epilepsies. CONCLUSIONS: Our single centre study confirms previous studies on the efficacy of VNS in children. A larger study using multivariate analysis to disentangle the contribution of different factors (such as age at implantation, aetiology, and epilepsy duration) is necessary to confirm our preliminary finding that younger age at VNS implantation might result in a better outcome. PMID- 26271819 TI - Densitometric evaluation of bone remodelling around Trabecular Metal Primary stem: a 24-month follow-up. AB - BACKGROUND: Today, an increasing number of total hip arthroplasty (THA) procedures are being performed. Osseointegration is a physiological phenomenon that leads to the direct anchorage of an implant by the formation of bony tissue around the implant without the growth of fibrous tissue at the bone-implant interface. Several factors may affect this phenomenon: some of these depend on the patient and others may depend on implant design and materials. Variations in periprosthetic bone mineral density (BMD) can be studied through several scans by dual energy X-ray absorptiometry (DEXA) around the femoral stem. AIMS: The purpose of this study is to investigate correlations between periprosthetic BMD and the factors affecting osseointegration. METHODS: We retrospectively analysed patients who underwent primary THA. In all the patients, Trabecular Metal Primary (TMP), a standard uncemented tapered stem with a proximal porous tantalum coating, was implanted. Preoperatively, postoperatively, 3 and 6 months, 1 year and 2 years after implantation, DEXA scans were performed around the femoral stem. The patients were matched for diagnosis, sex, BMD of the lumbar spine and contralateral femur, Body Mass Index and age. RESULTS: One hundred and eight patients (51 males and 57 females) with a mean age of 73 years were studied. Different BMD changing patterns were observed and a greater bone resorption was noted in all the conditions associated with poor bone quality. DISCUSSION: The proximal coating of Trabecular Metal Primary (TMP) seemed to be effective in promoting new bone formation in the proximal femur also in the conditions associated with poor bone quality. CONCLUSIONS: At the present time, DEXA is considered the most reliable tool for evaluating bone remodelling after THA. PMID- 26271820 TI - MicroRNA-Responsive Cancer Cell Imaging and Therapy with Functionalized Gold Nanoprobe. AB - Integration of cancer cell imaging and therapy is critical to enhance the theranostic efficacy and prevent under- or overtreatment. Here, a multifunctional gold nanoprobe is designed for simultaneous miRNA-responsive fluorescence imaging and therapeutic monitoring of cancer. By assembling with folic acid as the targeted moiety and a dye-labeled molecular beacon (MB) as the recognition element and signal switch, the gold nanoprobe is folate receptor-targeted delivered into the cancer cells, and the fluorescence is lighted with the unfolding of MB by intracellular microRNA (miRNA), resulting in an efficient method for imaging and detecting nucleic acid. The average quantity of miRNA-21 is measured to be 1.68 pg in a single HeLa cell. Upon the near-infrared irradiation at 808 nm, the real-time monitoring and assessing of photothermal therapeutic efficacy is achieved from the further enhanced fluorescence of the dye-labeled MB, caused by the high photothermal transformation efficiency of the gold nanocarrier to unwind the remaining folded MB and depart the dye from the nanocarrier. The fluorescence monitoring is also feasible for applications in vivo. This work provides a simple but powerful protocol with great potential in cancer imaging, therapy, and therapeutic monitoring. PMID- 26271817 TI - Exploring the Impact of Childhood Abuse on HIV Social and Attitudinal Factors Among Adults With and Without this History in Sub-Saharan Africa: Findings from NIMH Project Accept (HPTN 043). AB - Using data from four sites in three African countries, this community randomized study examined the association between childhood sexual and/or physical abuse (CSA and/or CPA) and HIV disclosure, HIV-related stigma, stress, and social support among adults with and without a history of abuse. A history of abuse among men was associated with higher levels of adult-reported stress and HIV related stigma, and with significantly lower rates of HIV test result disclosure to current partners. Women with a history of CSA and/or CPA had significantly higher perceived stigma, discrimination and stress. Although childhood abuse was significantly associated with adult stress and stigmatization, participants with histories of CSA and/or CPA also reported significantly higher perceived social support compared to people without such experiences. These findings may reflect support received in response to disclosure of CSA or CPA or emotional ambivalence in relationships that have been found to be associated with child abuse. We conclude that it is critical for HIV prevention interventions to advocate for the primary prevention of child abuse, for early identification of adolescents and adults who report experiencing childhood abuse, and to address stigma and stress related attitudinal, behavioral and relationship difficulties experiences as an aftermath of early abuse that increase their risk of HIV. PMID- 26271824 TI - Hepatitis A virus antibodies in Australian blood donors: implications for immunoglobulin sufficiency. AB - BACKGROUND: Passive immunisation is an important means of preventing hepatitis A in the most vulnerable populations in the event they are exposed. Trends in hepatitis A seroprevalence may impact on the production of effective immunoglobulin products for passive immunisation. METHODS: The seroprevalence of hepatitis A antibodies in blood donors in capital cities around Australia was measured using a commercial ELISA. Hepatitis A antibodies were quantified using the same commercial kit in a random sample of those who were seropositive. RESULTS: An estimated 51% (95% CI 48-54%) of Australian blood donors were seropositive for hepatitis A. Rates varied across the country and increased with age. The geometric mean titre (GMT) of those who were seropositive among our sample was 1246.8mIU/mL (geometric standard deviation 11.8mIU/mL) and increased with age. CONCLUSION: Comparison with published data supported an increase in seroprevalence in younger age groups. The seeming increase in seroprevalence among donors is encouraging regarding Australia's ability to maintain immunoglobulin sufficiency. However, the overall GMT of hepatitis A antibodies in donations may be prone to decrease as current donor cohorts age. PMID- 26271822 TI - Post-surgical infections and perioperative antibiotics usage in pediatric genitourinary procedures. AB - BACKGROUND: Post-surgical infections (PSIs) are a source of preventable perioperative morbidity. No guidelines exist for the use of perioperative antibiotics in pediatric urologic procedures. OBJECTIVE: This study reports the rate of PSIs in non-endoscopic pediatric genitourinary procedures at our institution. Secondary aims evaluate the association of PSI with other perioperative variables, including wound class (WC) and perioperative antibiotic administration. STUDY DESIGN: Data from consecutive non-endoscopic pediatric urologic procedures performed between August 2011 and April 2014 were examined retrospectively. The primary outcome was the rate of PSIs. PSIs were classified as superficial skin (SS) and deep/organ site (D/OS) according to Centers for Disease Control and Prevention guidelines, and urinary tract infection (UTI). PSIs were further stratified by WC1 and WC2 and perioperative antibiotic usage. A relative risk and chi-square analysis compared PSI rates between WC1 and WC2 procedures. RESULTS: A total of 1185 unique patients with 1384 surgical sites were reviewed; 1192 surgical sites had follow-up for inclusion into the study. Ten total PSIs were identified, for an overall infection rate of 0.83%. Of these, six were SS, one was D/OS, and three were UTIs. The PSI rate for WC1 (885 sites) and WC2 (307 sites) procedures was 0.34% and 2.28%, respectively, p < 0.01. Relative risk of infection in WC2 procedures was 6.7 (CI 1.75-25.85, p = 0.0055). The rate of infections in WC1 procedures was similar between those receiving and not receiving perioperative antibiotics (0.35% vs. 0.33%). All WC2 procedures received antibiotics. DISCUSSION: Post-surgical infections are associated with significant perioperative morbidity. In some studies, PSI can double hospital costs, and contribute to hospital length of stay, admission to intensive care units, and impact patient mortality. Our study demonstrates that the rate of PSI in WC1 operations is low, irrespective of whether the patient received perioperative antibiotics (0.35%) or no antibiotics (0.33%). WC2 operations were the larger source of morbidity with an infection rate of 2.28% and a 6.7 fold higher increase in relative risk. CONCLUSIONS: WC1 procedures have a rate of infection around 0.3%, which is independent of the use of perioperative antibiotics. WC2 procedures have a higher rate of infection, with a relative risk of 6.7 for the development of PSI, and should be the target of guidelines for periprocedural prophylaxis. PMID- 26271825 TI - Immunogenicity and performance of an enterovirus 71 virus-like-particle vaccine in nonhuman primates. AB - A vaccine against human enterovirus 71 (EV-A71) is urgently needed to combat outbreaks of EV-A71 and in particular, the serious neurological complications that manifest during these outbreaks. In this study, an EV-A71 virus-like particle (VLP) based on a B5 subgenogroup (EV-A71-B5 VLP) was generated using an insect cell/baculovirus platform. Biochemical analysis demonstrated that the purified VLP had a highly native procapsid structure and initial studies in vivo demonstrated that the VLPs were immunogenic in mice. The impact of VLP immunization on infection was examined in non-human primates using a VLP prime boost strategy prior to EV-A71 challenge. Rhesus macaques were immunized on day 0 and day 21 with VLPs (100 MUg/dose) containing adjuvant or with adjuvant alone (controls), and were challenged with EV-A71 on day 42. Complete blood counts, serum chemistry, magnetic resonance imaging (MRI) scans, and histopathology results were mostly normal in vaccinated and control animals after virus challenge demonstrating that the fatal EV-A71-B3 clinical isolate used in this study was not highly virulent in rhesus macaques. Viral genome and/or infectious virus were detected in blood, spleen or brain of two of three control animals, but not in any specimens from the vaccinated animals, indicating that VLP immunization prevented systemic spread of EV-A71 in rhesus macaques. High levels of IgM and IgG were detected in VLP-vaccinated animals and these responses were highly specific for EV-A71 particles and capsid proteins. Serum from vaccinated animals also exhibited similar neutralizing activity against different subgenogroups of EV-A71 demonstrating that the VLPs induced cross-neutralizing antibodies. In conclusion, our EV-A71-B5 VLP is safe, highly immunogenic, and prevents systemic EV-A71-B3 infection in nonhuman primates making it a viable attractive vaccine candidate for EV-A71. PMID- 26271823 TI - A 13-year survey of pneumococcal nasopharyngeal carriage in children with acute otitis media following PCV7 and PCV13 implementation. AB - BACKGROUND: This nasopharyngeal (NP) carriage surveillance study was requested by the European Agency for the Evaluation of Medicinal Products as a post-licensing commitment to determine whether the use of the pneumococcal conjugate vaccines (PCVs) including 7 then 13 valents (introduced in 2001 and 2010, respectively) caused a shift in the distribution of Streptococcus pneumoniae serotypes in children with acute otitis media and modified the resistance of this bacterial species to antibiotics. METHODS: Between 2001 and 2014, 121 pediatricians obtained nasopharyngeal swabs from children with acute otitis media aged 6-24 months. The swabs were analyzed by the French National Reference Centre for Pneumococci. Demographics, medical history and physical examination findings were recorded. RESULTS: Over the 13 years, among the 7991 enrolled patients, the proportion of PCV-vaccinated children (>=1 dose) increased (54.3-99.7%, p<0.001). Overall, pneumococcal carriage was reduced from 71.2% to 56.2% from 2001 to 2014 (p<0.001) and carriage of PCV7 serotypes (STs) from 44.5% to 1.2% (p<0.001). The carriage of 6 additional STs plus 6C increased from 17.2% to 24.3% from 2001 to 2010 (p<0.001) and decreased after PCV13 implementation (21.4-3.5%, p<0.001). The proportion of ST 19A carriage increased from 8.6% to 15.8% from 2001 to 2010 (p<0.001) and decreased to 1.2% in 2014. After PCV13 implementation, the most frequently carried non-PCV13 STs were ST 15B/C, 11A, 15A, and 35B. Penicillin non susceptible pneumococcal strains decreased from 67.1% in 2001 to 33.1% in 2014 (p<0.001). CONCLUSIONS: By the number of patients enrolled and the duration, this study is the largest performed to date. It allows to demonstrate a strong impact of PCVs and to describe the complex dynamics of pneumococcal carriage during AOM. As pneumococcal carriage decreased during AOM, a reduction in the incidence of pneumococcal AOM could be expected. PMID- 26271828 TI - Mucosal administration of raccoonpox virus expressing highly pathogenic avian H5N1 influenza neuraminidase is highly protective against H5N1 and seasonal influenza virus challenge. AB - We previously generated recombinant poxviruses expressing influenza antigens and studied their efficacy as potential highly pathogenic avian influenza (HPAI) vaccines in mice. While both modified vaccinia Ankara (MVA) and raccoon poxvirus (RCN) expressing hemagglutinin (HA) provided strong protection when administered by parenteral routes, only RCN-neuraminidase (NA) showed promise as a mucosal vaccine. In the present study we evaluated the efficacy of RCN-NA constructs by both intradermal (ID) and intranasal (IN) routes. Surprisingly, while RCN-NA completely protected mice when administered by the IN route, it failed to protect mice when administered by the ID route. After challenge, significantly less virus induced pathology was observed in the lungs of mice vaccinated with RCN-NA by the IN route as compared to the ID route. Furthermore, IN administration of RCN-NA elicited neutralizing antibodies detected in bronchoalveolar lavage (BAL) samples. We also determined the role of cellular immune responses in protection elicited by RCN-NA by depleting CD4 and CD8 T cells prior to challenge. Finally, we demonstrated for the first time that antibodies against NA can block viral entry in addition to viral spread in vitro. These studies demonstrate the importance of mucosal administration of RCN viral vectors for eliciting protective immune responses against the NA antigen. PMID- 26271826 TI - Rubella seronegativity in antenatal screening - Is it influenced by the introduction of universal childhood rubella immunization? AB - OBJECTIVE: This study examined the impact of rubella immunization, implemented in Hong Kong in phases since 1978, on antenatal rubella serological status in Chinese women. METHODS: In a retrospective cohort study, the incidence of antenatal rubella seronegative status in our parturients managed from 1998 to 2013 was analyzed by their year-of-birth as follows: <1965 (no childhood immunization), 1965-1982 (single dose at Primary 6), and >=1983 (two doses at age 12 months and 12 years), adjusting for other factors including age, parity, body mass index, place-of-birth status and hepatitis B surface antigen (HBsAg) status. FINDINGS: Rubella seronegativity decreased from 12.9%, 10.5%, to 9.8% respectively, and correlated inversely (P<0.001) with year-of-birth cohorts. Despite similar demographic profiles, this correlation was found only in Hong Kong-born women (from 12.6%, 7.5% to 6.5% respectively), who also had significant lower incidences of rubella seronegativity (OR 0.73, 0.31 and 0.29 respectively) and HBsAg seropositivity (OR 1.09, 0.63 and 0.48 respectively) than China-born women. On regression analysis, rubella seronegativity was actually significantly increased following the implementation of immunization (aOR 1.20) while it was the reverse for non-residents (aOR 0.61). CONCLUSION: Although rubella seronegativity decreased with immunization, the effect was less than expected when adjusted for other risk factors. PMID- 26271829 TI - Reduced dose human papillomavirus vaccination: an update of the current state-of the-art. AB - Human papillomavirus (HPV) infection is the primary cause of genital warts, some oropharyngeal cancers and anogenital cancers, including cervical, vagina, vulvar, anal and penile cancers. Primary prevention of cervical cancer requires the prevention of high-risk HPV infections, particularly HPV genotypes 16 and 18. Both Gardasil(r) and Cervarix(r) vaccines when administered by a three-dose schedule have been demonstrated to be effective against cervical, vulva, and vaginal cancer precursors from vaccine genotypes in phase III clinical trials, and post-marketing studies; Gardasil(r) vaccine also offers additional protection against anal cancer precursors. However, high costs of HPV vaccines and the logistics of delivering a three-dose schedule over 6 months are challenging in countries with limited resources. Several studies have demonstrated non inferiority in antibody response between adolescents (9-15 years old) who received two doses (6 months apart) and women (>15 years old) who received the standard three-dose schedule. These studies provided evidence for the World Health Organization and European Medical Association to revise its recommendation to give two instead of three doses of HPV vaccine to adolescents below 15 years of age, provided the 2nd dose is given 6 months apart. Although reduced dose schedules can alleviate costs and logistics associated with HPV vaccination, especially in resource-poor countries, there are still gaps in this area of research, particularly regarding long-term protection. This review discusses the findings on antibody response and clinical outcomes in studies evaluating reduced dose HPV schedules, and highlights the important considerations of its implementation. In addition, other important immunological biomarkers that may be associated with long-term protection are highlighted and discussed. PMID- 26271827 TI - Incidence of medically attended influenza infection and cases averted by vaccination, 2011/2012 and 2012/2013 influenza seasons. AB - BACKGROUND: We estimated the burden of outpatient influenza and cases prevented by vaccination during the 2011/2012 and 2012/2013 influenza seasons using data from the United States Influenza Vaccine Effectiveness (US Flu VE) Network. METHODS: We defined source populations of persons who could seek care for acute respiratory illness (ARI) at each of the five US Flu VE Network sites. We identified all members of the source population who were tested for influenza during US Flu VE influenza surveillance. Each influenza-positive subject received a sampling weight based on the proportion of source population members who were tested for influenza, stratified by site, age, and other factors. We used the sampling weights to estimate the cumulative incidence of medically attended influenza in the source populations. We estimated cases averted by vaccination using estimates of cumulative incidence, vaccine coverage, and vaccine effectiveness. RESULTS: Cumulative incidence of medically attended influenza ranged from 0.8% to 2.8% across sites during 2011/2012 and from 2.6% to 6.5% during the 2012/2013 season. Stratified by age, incidence ranged from 1.2% among adults 50 years of age and older in 2011/2012 to 10.9% among children 6 months to 8 years of age in 2012/2013. Cases averted by vaccination ranged from 4 to 41 per 1000 vaccinees, depending on the study site and year. CONCLUSIONS: The incidence of medically attended influenza varies greatly by year and even by geographic region within the same year. The number of cases averted by vaccination varies greatly based on overall incidence and on vaccine coverage. PMID- 26271832 TI - Ethical considerations for designing GBS maternal vaccine efficacy trials in low middle income countries. AB - Many in the scientific community agree that a randomized, placebo-controlled trial would offer the most scientifically rigorous study design for establishing the efficacy of a Group B Streptococcus (GBS) vaccine administered to pregnant women for the prevention of invasive GBS disease in young infants. There are compelling reasons to conduct such a trial in low-middle income countries (LMICs) with a high burden of disease, such as South Africa, and to adopt an add-on trial design in which participants are randomized to receive the GBS vaccine or placebo in addition to the locally available standard of care. Yet there is a longstanding debate about whether trials in LMICs should offer participants the worldwide best available standard of care. In this article, we examine both the risk-benefit profile and the potential for exploitation with an add-on trial design in the context of the locally available standard of care in South Africa. Our analysis suggests that providing the local standard of care to participants in this case may be not only more scientifically valuable but also more ethically acceptable than attempting to provide the worldwide best available standard of care in the South African setting. Moreover, the example of GBS in the South African setting can help to elucidate important ethical considerations for determining the acceptability of testing vaccine efficacy in the context of locally available rather than the worldwide best available standard of care in Phase III trials of other new maternal vaccines. PMID- 26271830 TI - Evaluation of hyaluronic acid-based combination adjuvant containing monophosphoryl lipid A and aluminum salt for hepatitis B vaccine. AB - Here, monophosphoryl lipid A (MPLA) and aluminum salt (Alum) were introduced into a hyaluronic acid (HA)-based combination vaccine adjuvant for hepatitis B vaccine (HBV). Although Alum is a well-known hepatitis B vaccine adjuvant that induces an enhanced humoral immune response, it cannot induce the cellular immune responses. On the other hand, MPLA has been generally reported to promote IFN-gamma production via antigen-specific CD4(+) T cells, but it is not water soluble as a result of its long hydrophobic alkyl chains. To this end, water insoluble MPLA could be solubilized in an aqueous solution with the help of HA, which contains many carboxyl and hydroxyl groups that can be used to attach to the hydroxyl head groups of MPLA via hydrogen bonds. Three groups of mice were treated with either hepatitis B surface antigen (HBsAg) alone, HBsAg_Alum complex, or HBsAg_Alum_MPLA/HA complex. The group immunized with the HBsAg_Alum_MPLA/HA complex exhibited a high increase in cellular immune response as well as in humoral immune response relative to the other two groups. The antibody, cytokine and T cell levels were most elevated in the group of mice immunized with HBsAg_Alum_MPLA/HA complex, even at a 1MUg/mice dose, and the magnitude was still maintained even after 8 weeks. Specifically, the antibody value was 120 times larger in mice vaccinated with HBsAg_Alum_MPLA/HA complex than in mice vaccinated with HBsAg_Alum complex designed similar to commercially available hepatitis B vaccine, Engerix B. The cytokine and T cell proliferation levels were 2 times and 6 times larger in mice adjuvanted with HBsAg_Alum_MPLA/HA complex than in those vaccinated with HBsAg_Alum. The results therefore indicate that incorporating MPLA and Alum with HA can be a potent strategy to increase both the magnitude and the persistence of HBsAg-specific immune responses to protect hosts against hepatitis B virus infection. PMID- 26271833 TI - Critical review of current and emerging quantification methods for the development of influenza vaccine candidates. AB - Significant improvements in production and purification have been achieved since the first approved influenza vaccines were administered 75 years ago. Global surveillance and fast response have limited the impact of the last pandemic in 2009. In case of another pandemic, vaccines can be generated within three weeks with certain platforms. However, our Achilles heel is at the quantification level. Production of reagents for the quantification of new vaccines using the SRID, the main method formally approved by regulatory bodies, requires two to three months. The impact of such delays can be tragic for vulnerable populations. Therefore, efforts have been directed toward developing alternative quantification methods, which are sensitive, accurate, easy to implement and independent of the availability of specific reagents. The use of newly-developed antibodies against a conserved region of hemagglutinin (HA), a surface protein of influenza, holds great promises as they are able to recognize multiple subtypes of influenza; these new antibodies could be used in immunoassays such as ELISA and slot-blot analysis. HA concentration can also be determined using reversed phase high performance liquid chromatography (RP-HPLC), which obviates the need for antibodies but still requires a reference standard. The number of viral particles can be evaluated using ion-exchange HPLC and techniques based on flow cytometry principles, but non-viral vesicles have to be taken into account with cellular production platforms. As new production systems are optimized, new quantification methods that are adapted to the type of vaccine produced are required. The nature of these new-generation vaccines might dictate which quantification method to use. In all cases, an alternative method will have to be validated against the current SRID assay. A consensus among the scientific community would have to be reached so that the adoption of new quantification methods would be harmonized between international laboratories. PMID- 26271831 TI - Chitosan-based mucosal adjuvants: Sunrise on the ocean. AB - Mucosal vaccination, which is shown to elicit systemic and mucosal immune responses, serves as a non-invasive and convenient alternative to parenteral administration, with stronger capability in combatting diseases at the site of entry. The exploration of potent mucosal adjuvants is emerging as a significant area, based on the continued necessity to amplify the immune responses to a wide array of antigens that are poorly immunogenic at the mucosal sites. As one of the inspirations from the ocean, chitosan-based mucosal adjuvants have been developed with unique advantages, such as, ability of mucosal adhesion, distinct trait of opening the junctions to allow the paracellular transport of antigen, good tolerability and biocompatibility, which guaranteed the great potential in capitalizing on their application in human clinical trials. In this review, the state of art of chitosan and its derivatives as mucosal adjuvants, including thermo-sensitive chitosan system as mucosal adjuvant that were newly developed by author's group, was described, as well as the clinical application perspective. After a brief introduction of mucosal adjuvants, chitosan and its derivatives as robust immune potentiator were discussed in detail and depth, in regard to the metabolism, safety profile, mode of actions and preclinical and clinical applications, which may shed light on the massive clinical application of chitosan as mucosal adjuvant. PMID- 26271834 TI - Extension of the celiac intestinal antibody (CIA) pattern through eight antibody assessments in fecal supernatants from patients with celiac disease. AB - BACKGROUND: Detection of anti-transglutaminase, anti-endomysium and anti-gliadin antibodies is commonly used to screen celiac disease patients. Besides that in serum, these antibodies are detectable in culture supernatants of oral, duodenal and colonic biopsy samples, saliva, gut lavage fluid samples, and fecal supernatants. Our aim was to extend the intestinal antibody pattern in fecal supernatants from patients with celiac disease. METHODS: The fecal supernatants obtained from 25 celiac disease patients and 12 healthy volunteers were used to determine IgA and IgG1 anti-endomysium by immunofluorescence analysis, IgA and IgG anti-transglutaminase, IgA and IgG anti-deamidated gliadin peptides, IgA/IgG anti-transglutaminase/deamidated gliadin peptides and IgA anti-actin by enzyme linked immunosorbent assay. RESULTS: IgA anti-endomysium were found in 11 of 25 (44.0%) celiac disease patients and in none of healthy volunteers (p=0.0066). The levels of IgA anti-transglutaminase, IgA anti-deamidated gliadin peptides, IgA/IgG anti-transglutaminase/deamidated gliadin peptides and IgA anti-actin determined in celiac disease patients were significantly higher (p=0.0005, p=0.0018, p=0.0061 and p=0.0477, respectively) than those measured in healthy volunteers. The ROC curve analysis showed a diagnostic significance in IgA anti transglutaminase (AUC=0.862, p<0.0001), IgA anti-deamidated gliadin peptides (AUC=0.822, p<0.0001) and IgA/IgG anti-transglutaminase/deamidated gliadin peptides (AUC=0.783, p=0.0003) fecal tests. CONCLUSIONS: Our data extend the intestinal antibody pattern detectable in fecal supernatants, thus increasing the knowledge in the humoral immunity of celiac disease. Further studies are needed to better evaluate the role of fecal antibody tests in identifying celiac disease patients. PMID- 26271836 TI - The transition from fellowship: much ado about quality. PMID- 26271835 TI - The history of China's maternal and child health care development. AB - The history of maternal and child health (MCH) development in China can be divided into six stages: before 1949 when the People's Republic of China was founded, traditional Chinese medicine shielded women's and children's health while modern medicine began to bud; 1949-1966, the MCH system was established and gradually improved; 1966-1976, the decade of the Cultural Revolution, the road to improve MCH twisted and turned along with the political instability; 1976-1990, especially after the "Reform" and "Opening Up", China's MCH care had been booming and the MCH status continued to improve with the rapid social and economic development; 1990-2008, with the booming economy, MCH care gained increasingly national and international attention. Through improving legislation and investment, China made great strides in the improvement of MCH. After 2009, the comprehensive health care reform laid an institutional basis for the development of MCH and promotion of health equity. PMID- 26271837 TI - The Misunderstood Asthma of Theodore Roosevelt. AB - In this special article, we examine the asthma of President Theodore "TR" Roosevelt (1858-1919). Through a comprehensive review of thousands of source documents, and a modern understanding of asthma, we examine several misunderstandings, including the longstanding assertion that TR's illness was "psychosomatic." TR's respiratory problems began in early childhood, and the historical record provides strong evidence for poorly controlled, persistent asthma. Like many patients, his asthma entered a relatively quiescent stage during adolescence, coincident with initiation of a vigorous exercise program when TR was 12 years old. Nevertheless, TR continued to suffer serious asthma exacerbations, both in adolescence and adulthood. Although psychosocial issues affect most chronic diseases, there is little (if any) support for assertions that TR's asthma was psychosomatic. We believe that TR's childhood struggles with asthma, and the misconception that he vanquished his illness through exercise, were experiences that profoundly affected his worldview. TR is known for his appreciation of life's struggles and for a bedrock belief that people can create major change with sufficient motivation and hard work. In different ways, misunderstandings about asthma contributed to the early development of these personal characteristics. Together with later experiences, they contributed to a lifetime of action that changed modern history. PMID- 26271838 TI - Clinical Characterization of LRPAP1-Related Pediatric High Myopia. PMID- 26271840 TI - Whole Exome Profiling of Ocular Surface Squamous Neoplasia. PMID- 26271839 TI - Five-Year Clinical Trial on Atropine for the Treatment of Myopia 2: Myopia Control with Atropine 0.01% Eyedrops. AB - PURPOSE: To compare the safety and efficacy of different concentrations of atropine eyedrops in controlling myopia progression over 5 years. DESIGN: Randomized, double-masked clinical trial. PARTICIPANTS: A total of 400 children originally randomized to receive atropine 0.5%, 0.1%, or 0.01% once daily in both eyes in a 2:2:1 ratio. METHODS: Children received atropine for 24 months (phase 1), after which medication was stopped for 12 months (phase 2). Children who had myopia progression (>=-0.50 diopters [D] in at least 1 eye) during phase 2 were restarted on atropine 0.01% for a further 24 months (phase 3). MAIN OUTCOME MEASURES: Change in spherical equivalent and axial length over 5 years. RESULTS: There was a dose-related response in phase 1 with a greater effect in higher doses, but an inverse dose-related increase in myopia during phase 2 (washout), resulting in atropine 0.01% being most effective in reducing myopia progression at 3 years. Some 24%, 59%, and 68% of children originally in the atropine 0.01%, 0.1%, and 0.5% groups, respectively, who progressed in phase 2 were restarted on atropine 0.01%. Younger children and those with greater myopic progression in year 1 were more likely to require re-treatment. The lower myopia progression in the 0.01% group persisted during phase 3, with overall myopia progression and change in axial elongation at the end of 5 years being lowest in this group ( 1.38+/-0.98 D; 0.75+/-0.48 mm) compared with the 0.1% (-1.83+/-1.16 D, P = 0.003; 0.85+/-0.53 mm, P = 0.144) and 0.5% (-1.98+/-1.10 D, P < 0.001; 0.87+/-0.49 mm, P = 0.075) groups. Atropine 0.01% also caused minimal pupil dilation (0.8 mm), minimal loss of accommodation (2-3 D), and no near visual loss compared with higher doses. CONCLUSIONS: Over 5 years, atropine 0.01% eyedrops were more effective in slowing myopia progression with less visual side effects compared with higher doses of atropine. PMID- 26271841 TI - The First 100 Eyes of Standardized Descemet Stripping Automated Endothelial Keratoplasty versus Standardized Descemet Membrane Endothelial Keratoplasty. AB - PURPOSE: To compare results of the first 100 eyes of Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) that were performed with a standardized technique at a single institution. DESIGN: Single-center, retrospective case series. PARTICIPANTS: The first 100 eyes of standardized DSAEK and DMEK that underwent surgery for Fuchs corneal dystrophy at our center. We excluded patients with prior ocular surgery other than cataract surgery to limit confounding variables. METHODS: Best spectacle corrected visual acuity (BSCVA; in logarithm of the minimal angle of resolution [logMAR] units) was obtained and specular microscopy of donor corneal tissue was performed before surgery. Postoperative complications, BSCVA, and the percent of endothelial cell loss (ECL) recorded at 6 months were compared with the Student t test. Patients with pre-existing ocular comorbidity that impacted visual potential such as macular degeneration, amblyopia, advanced glaucoma, and other optic neuropathies were excluded from the analysis of visual acuity, but were included for the outcomes of complications and ECL. MAIN OUTCOME MEASURES: Visual acuity improvement, ECL 6 months after surgery, postoperative complications, iatrogenic primary graft failure (IPGF), and rebubbling. RESULTS: Of the 200 eyes, 62 DSAEK eyes and 70 DMEK eyes had 6-month BSCVA available and no vision limiting comorbidities. Mean BSCVA increased from 0.41+/-0.19 logMAR and 0.27+/ 0.11 logMAR before surgery to 0.20+/-0.13 logMAR and 0.11+/-0.13 logMAR 6 months after DSAEK and DMEK, respectively (P<0.001). Seventy-one DSAEK eyes and 70 DMEK eyes had 6-month ECL data available: ECL was 25.9+/-14.0% after DSAEK and 27.9+/ 16.0% after DMEK (P=0.38). There were no IPGFs in the DSAEK cohort and there were 4 of 100 IPGFs after DMEK (P=0.12). Rebubbling was performed in 2 of 100 eyes after DSAEK and in 6 of 100 eyes after DMEK (P=0.28). CONCLUSIONS: Compared with DSAEK, DMEK provided better visual recovery and comparable 6-month ECL. The DMEK group had a higher, although not statistically significant, percentage of rebubbling procedures and IPGFs. PMID- 26271842 TI - Factors Associated with Recurrence of Age-Related Macular Degeneration after Anti Vascular Endothelial Growth Factor Treatment: A Retrospective Cohort Study. AB - PURPOSE: To investigate the predictive factors associated with recurrence after anti-vascular endothelial growth factor (VEGF) treatment for neovascular age related macular degeneration (AMD). DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 343 eyes of 326 patients with subfoveal neovascular AMD who were treated with an as-needed regimen after 3 monthly loading doses of intravitreal ranibizumab. METHODS: Patients were followed up by an as-needed regimen for more than 1 year after the first injection. Baseline data and CFH I62V and ARMS2 A69S polymorphisms were analyzed for their association with recurrence after anti-VEGF treatment. Regression analysis was used to identify independent predictors of visual acuity (VA) prognosis. MAIN OUTCOME MEASURES: The primary end point was the presence or absence of recurrence. The secondary end point was VA improvement. RESULTS: In total, 236 eyes (68.8%) showed complete resolution of retinal exudative change after the 3 loading injections, and 81 eyes (34.3%) experienced no recurrence during the first year. Of the 236 eyes, 139 (58.9%) were followed for more than 2 years and 35 (25.2%) showed no recurrent retinal exudation during 24 months. Visual acuity improvement was significantly better in eyes without recurrence than in eyes with recurrence during the 2-year period. Baseline characteristics and genotypes had no influence on response to ranibizumab loading treatment. Stepwise analysis revealed that age (P<0.001), subtype of AMD (P=0.041), and VA at baseline (P<0.001) were associated with VA at 24 months. Older patients (P=0.006) and male patients (P=0.018) tended to require re-treatment for recurrence during the first year, yet the statistical significance disappeared when evaluated in 2 years. The subtypes of neovascular AMD were solely associated with the interval to the recurrence, which was shorter in eyes with polypoidal choroidal vasculopathy (PCV) than in eyes with typical AMD (P=0.015). CONCLUSIONS: Older age and male sex may predict recurrence after 3 monthly ranibizumab injections, and PCV may be associated with shorter interval to recurrence. Predicting the risk of recurrence would help us to choose the most appropriate follow-up treatment strategy for patients with AMD. PMID- 26271844 TI - The good old new old days. PMID- 26271845 TI - Prescriptions and drugs: A new generation. PMID- 26271846 TI - Erratum. PMID- 26271847 TI - Fix a jaw off the floor. PMID- 26271848 TI - Patient safety: Cochlear implants. PMID- 26271849 TI - Continuing development: The blame game. PMID- 26271851 TI - Feature: Why am I feeling stressed? PMID- 26271843 TI - Corneal Changes in Children after Unilateral Cataract Surgery in the Infant Aphakia Treatment Study. AB - PURPOSE: We report endothelial cell (EC) characteristics and central corneal thickness (CCT) from the Infant Aphakia Treatment Study (IATS) patients at the 5 year examination. DESIGN: Randomized, controlled trial of the treatment of unilateral cataract with aphakic contact lens (CL) versus primary intraocular lens (IOL) implant. PARTICIPANTS: A total of 114 infants with unilateral cataract. METHODS: The EC density, coefficient of variation (CV), and percent hexagonal cells were measured by noncontact specular microscopy. The CCT was measured using contact pachymetry. Fellow eyes served as controls. MAIN OUTCOME MEASURES: Mean differences between treated and fellow eyes of CL and IOL groups were compared with a paired t test. A 1-way analysis of variance model and the Tukey-Kramer multiple comparison procedure were used to assess the effect of a diagnosis of glaucoma or glaucoma suspect. RESULTS: A total of 105 subjects (52 with CLs, 53 with IOLs) had specular microscopy or corneal thickness data recorded. Mean EC densities were higher in aphakic eyes compared with fellow eyes (3921 vs. 3495 cells/mm2, P<0.0001). Mean CV was higher (27 vs. 24, P=0.0002) and mean percent hexagonal cells was lower (72% vs. 76%, P=0.002) in aphakic eyes compared with fellow eyes. Mean CCT of aphakic eyes was higher than in controls (637 vs. 563 MUm, P<0.0001). There was no difference in EC density in eyes treated with IOLs compared with fellow eyes (3445 and 3487 cells/mm2, P=0.68). Means for CV (25 vs. 24, P=0.07) and percent hexagonal cells (74 vs. 76%, P=0.27) were also not significantly different. Mean CCT was higher in eyes with IOLs (605 vs. 571 MUm, P<0.0001) compared with fellow eyes. Compared with treated eyes without glaucoma or glaucoma suspect, treated eyes with glaucoma had lower EC density (3289 vs. 3783 cells/mm2, P=0.03) and treated eyes with glaucoma suspect had greater mean corneal thickness (660 vs. 612 MUm, P=0.0036). CONCLUSIONS: Cataract extraction during infancy with IOL implantation was not associated with a reduced EC count in treated compared with fellow eyes, although CCT was increased. Extended-wear aphakic CLs may cause corneal polymegathism with increased EC density and CCT. Glaucoma diagnosis was associated with reduced EC counts and increased CCT. PMID- 26271850 TI - In practice: Alveolar nerve injuries. PMID- 26271852 TI - We need your help. PMID- 26271855 TI - A day in the life: At the centre of innovation. PMID- 26271854 TI - Summer lecture: Looking to the future at the Anniversary Lecture. PMID- 26271858 TI - Parental knowledge gap leaving NHS with L22M early dental care bill. PMID- 26271860 TI - 'A good relationship and good communication are not sufficient for patient centred care'. PMID- 26271861 TI - NHS Health Checks in a primary care dental setting - an opportunity for the profession to maximise uptake for public health partners? AB - This opinion piece considers an opportunity for primary dental care practitioners to work in partnership with public health teams to maximise the uptake of the NHS Health Check. Public Health England and Local Authority partners remain committed to offering the NHS Health Check to those aged 40-74 years old. The programme previously explored alternative points of delivery - such as community pharmacists. This piece discusses and reflects on the efforts within Manchester to use skill mix in primary dental care services and widen access to target individuals eligible for an NHS Health Check. The pilot schemes in Manchester illustrated the willingness and enthusiasm for primary care dentists to embrace change and work alongside new partners to deliver patient benefit beyond the provision of dental care. However, substantial barriers to implementation prevented the desired level of progress. PMID- 26271862 TI - Are e-cigarettes a gateway to smoking or a pathway to quitting? AB - Over recent years there has been a massive increase in the usage of electronic cigarettes (e-cigs) by the general public. There are mixed views regarding the safety and efficacy of e-cigs, even among healthcare professionals. While some individuals view e-cigs as a public health concern, others recommend them as a safe alternative to conventional cigarettes for smokers who are willing to quit. Since e-cigs are a new phenomena, many clinicians are unaware of their impact on users (known as vapers), who may seek medical advice regarding their use. This clinical review aims to educate healthcare professionals regarding the advantages and disadvantages of e-cigarettes and to discuss whether e-cigarettes help users quit smoking or whether they renormalise smoking. This article will describe the contents of e-cigs and how they are used, the history, advantages, disadvantages and then balance the positive and negative aspects of their use. Due to the lack of long-term follow up of the health effects of e-cigarettes, caution is advised with their use. PMID- 26271868 TI - Blood investigations prior to oral surgery for suspected alcohol-induced coagulopathy. Are they necessary? AB - OBJECTIVE: To evaluate the current practice of pre-oral surgery haematological investigation in patients with disclosed regular and prolonged high alcohol consumption above the national recommendation for coagulopathy due to potential alcohol induced liver impairment. DESIGN: Retrospective analysis of data.Setting University of Bristol Dental Hospital, United Kingdom, 2013.Subjects Adults (over 16 years old) with a reported high alcohol intake with no history of non-alcohol related liver impairment or pre-existing coagulopathy.Main outcome measures Alcohol and bleeding history recorded, haematology test requested with results and actions for abnormal results. RESULTS: From a sample size of 58 patients, 75.9% of cases had their alcohol intake recorded; only 10.3% of cases had the duration of drinking recorded. Bleeding history was recorded in 82.9% of cases to which 6.9% of cases had a positive bleeding history. The most common combination of tests requested was full blood count, coagulation screen and liver function test. In 46.6% of cases, results were out of range - in all cases but 1, the patients abnormal haematology results were not followed up further. CONCLUSION: It was found that 1.7% of cases met the locally agreed standard (from best available evidence) that haematology requests, including full blood count and coagulation screen, should only be undertaken in those with disclosed high alcohol intake and positive bleeding history. A consistent bleeding history and alcohol intake should always be documented thoroughly. PMID- 26271869 TI - A randomised clinical study to evaluate the efficacy of alcohol-free or alcohol containing mouthrinses with chlorhexidine on gingival bleeding. AB - OBJECTIVES: Gingival bleeding following twice-daily use of 0.2% w/v chlorhexidine digluconate mouthrinse with and without alcohol (0.2% CHX-alcohol; 0.2% CHX alcohol-free, respectively) and brushing with a standard fluoride toothpaste was compared to brushing alone. METHODS: Three hundred and nineteen subjects with mild-to-moderate gingivitis (with >=16 gradable permanent teeth including four molars, bleeding after brushing and >=20 bleeding sites) completed this randomised, examiner-blinded, parallel-group study. A prophylaxis was performed at baseline. Gingival Severity Index (GSI; primary objective), Gingival Index (GI) and Plaque Index (PI) were assessed at baseline and after 6 weeks of treatment. Adverse events (AEs) were recorded throughout the study. RESULTS: Between treatment differences at week 6 demonstrated significantly lower GSI for the 0.2% CHX-alcohol and 0.2% CHX-alcohol-free groups compared to brushing alone (primary endpoint; treatment difference -0.061 [95% CI -0.081, -0.041] and -0.070 [95% CI -0.090, -0.050], respectively; both p <0.0001). There were also significant reductions in GI and PI for the 0.2% CHX-alcohol and 0.2% CHX-alcohol free groups compared to brushing alone (all p <0.0001). The proportion of subjects reporting >=1 treatment-related adverse events (TRAEs) was 27.8% (0.2% CHX-alcohol), 24.8% (0.2% CHX-alcohol-free) and 3.7% (brushing alone). CONCLUSIONS: Chlorhexidine mouthrinse with or without alcohol as an adjunct to brushing with regular fluoride toothpaste significantly reduces bleeding scores, plaque and gingival inflammation compared to brushing alone. TRAEs are characteristic of those associated with the use of chlorhexidine and are similar for both mouthrinses. PMID- 26271870 TI - Perception of studying dental law and ethics among postgraduate dental students in the UK. AB - Law and ethics is an integral part of medical and dental professional practice. The subject is touched upon in the undergraduate curriculum. Historically, dentists interested in postgraduate study in this subject have accessed courses on medical law and ethics. While there are areas of shared interest (for example, consent, confidentiality) there are differences in emphasis and content (for example, end of life care, organ transplants, etc) which are not relevant to dentistry. A new postgraduate certificate (PgCert) course was approved by the University of Bedfordshire designed specifically for dental practitioners, making it the only university accredited course in the UK that is specific to dental staff. Students' perception of the subject of dental law and ethics at a postgraduate level was not known. The first PgCert student cohort was assessed at the start and the end of the course using two questionnaires. Sixteen students, all qualified dental practitioners working in the UK, took part. The perception toward the subject of dental law and ethics was in-line with the current guideline and regulations governing the dental profession. Perception of dental law was clearer at the end of the course compared to the beginning while dental ethics remained a challenging subject. PMID- 26271871 TI - Smart dental practice: capitalising on smart mobile technology. AB - To keep pace with consumer adoption of smart mobile devices, such as smartphones and tablets, and the applications ('apps') developed for these devices, dental professionals should consider how this technology could be used to simultaneously improve both patient service experiences and dental practice management. Using U Commerce as a theoretical lens, this article discusses the potential value of smart mobile technology to the dental practice context, with a particular focus on the unique and customisable capabilities of apps. To take full advantage of this technology, a process is outlined for identifying and designing bespoke dental apps that takes into account the unique advantages of these devices. Dental practices, with increasing financial and competitive pressures, may improve the efficiency and profitability of operations and better manage patients, employees and stakeholders by integrating smart mobile technology. PMID- 26271883 TI - Simon Edward Lewis. PMID- 26271884 TI - Brian Birkett. PMID- 26271885 TI - A national survey of the public's views on quality in dental care. AB - BACKGROUND: There is a lack of evidence and poor understanding of quality measurement and improvement in dentistry. The aim of this study was to undertake a nationally representative survey of the public in England to explore their views on the meaning of quality in dentistry. METHODS: A cross sectional survey of the adult population (18 years and over) of England was undertaken. A sample size of 500 was set to provide a precision to plus or minus 5% after allowing for item non-response. A quota sampling approach was used, with predetermined quotas set for sex, age, working status and tenure to ensure the sample was nationally representative. Question selection and design were informed by the literature and a series of interviews with the public. Simple content analysis was used to identify themes in the responses to open questions. Dental service use, gender, age, ethnicity and social class were recorded. Frequency distributions were computed and outputs were cross-tabulated with various population sub-group categories. RESULTS: Five hundred and thirteen people were interviewed. Approximately 20% of patients reported that their care was suboptimal; a third thought it was poor value for money and 20% did not trust their dentist. Good interpersonal communication, politeness and being put at ease were the most important factors that elicited positive responses. Negative factors were cost of care and waiting times. In making an assessment of quality, access (40% of all responses), technical quality of care (35%), professionalism (30%), hygiene/cleanliness (30%), staff attitude (27%), pain-free treatment (23%), value for money (22%), and staff putting patients at ease (21%) all emerged as important factors. CONCLUSIONS: Quality in dentistry is multi-dimensional in nature, and includes different elements and emphases to other areas of healthcare. The results will inform the development of a measure of quality in dentistry. PMID- 26271886 TI - Differential regulation of angiotensin converting enzyme 2 and nuclear factor kappaB by angiotensin II receptor subtypes in type 2 diabetic kidney. AB - Angiotensin II (Ang II) acts through Angiotensin Converting Enzyme (ACE)/Ang II type 1 receptor (AT1R) axis to promote renal failure whereas the Ang II type 2 receptor (AT2R)/Angiotensin Converting Enzyme 2 (ACE2)/Ang1-7/Mas axis constitutes the protective arm of Renin Angiotensin System (RAS). Though Ang II has been known to activate the Nuclear Factor-kappaB (NF-kappaB) signalling pathway through different receptor subtype(s) in different tissues under various diseases, the subtype orchestrating this stimulation in type 2 diabetic kidney remains elusive. ACE2, a protective monocarboxypeptidase, responsible for conversion of Ang II to Ang1-7, opposes the deleterious effects of RAS pathway but how its expression is altered with blockade of AT1R and AT2R is not yet known. Hence, the present study was conceived to understand the regulation of NF kappaB and ACE2 by using specific AT1 and AT2 receptor antagonists in non-genetic model of type 2 diabetic nephropathy. Our results show that the AT1R and AT2R antagonists lead to the repression and activation of NF-kappaB signalling pathway, respectively which suggests the role of AT1R in NF-kappaB activation. The blockade of AT2R led to an increase in ACE2 expression, which may be a compensatory response to the drastically increased inflammatory mediators and oxidative stress in the diabetic kidney. To the best of our knowledge, this is the first study showing the differential regulation of NF-kappaB and ACE2 by Ang II receptor subtypes and thus this study improves our understanding regarding regulation of inflammatory cascade and ACE2 by AT1R and AT2R in type 2 diabetic kidney, which may help in designing novel strategies to combat the disease in future. PMID- 26271887 TI - Behavioral and thyroid effects of in utero and lactational exposure of Sprague Dawley rats to the polybrominated diphenyl ether mixture DE71. AB - Exposure of rodents during gestation and lactation to polybrominated diphenyl ethers (PBDEs) has been reported to disrupt neurobehavioral function in offspring, as well as to disrupt thyroid function. To assess this we evaluated development and behavior after gestational and lactational exposure to the technical PBDE mixture DE71. Pregnant Sprague-Dawley rats were exposed to 0, 0.3, 3.0 or 30 mg/kg/day of DE71 from gestation day 1 to postnatal day (PND) 21 and were assessed on a wide range of behavioral functions from early postnatal period until old age (PND 450). DE71 exposure decreased thyroid hormone levels (T3 and T4) in mothers and offspring with offspring being more sensitive that mothers. Developmental landmarks, neuromotor function, anxiety, learning and memory were not affected by DE71 at any age. DE71 produced small changes in motor activity rearing only at PND 110 but not at any other age and no other activity measure was altered by DE71. Cholinergic sensitivity measured by nicotine-stimulated motor activity was not affected by perinatal DE71 exposure. Acoustic startle responses were potentiated by DE71 at PND 90 indicating delayed effects on sensory reactivity. Habituation was measured in motor activity tests at five ages but was not altered by DE71 at any age. Habituation measured in startle tests was also not affected by exposure to DE71. For thyroid hormone levels at PND 21, the lowest adverse effect level was 3.0 mg/kg. Few behavioral effects were observed and the lowest adverse effect level was 30 mg/kg. Our results confirm that DE71 produces transient effects on thyroid hormone levels but does not result in learning or motor impairment and does not alter non-associative learning (habituation). PMID- 26271889 TI - Smartphone ECG aids real time diagnosis of palpitations in the competitive college athlete. AB - IMPORTANCE: Rapidly detecting dangerous arrhythmias in a symptomatic athlete continues to be an elusive goal. The use of handheld smartphone electrocardiogram (ECG) monitors could represent a helpful tool connecting the athletic trainer to the cardiologist. OBSERVATIONS: Six college athletes presented to their athletic trainers complaining of palpitations during exercise. A single lead ECG was performed using the AliveCor Heart Monitor and sent wirelessly to the Team Cardiologist who confirmed an absence of dangerous arrhythmia. CONCLUSIONS AND RELEVANCE: AliveCor monitoring has the potential to enhance evaluation of symptomatic athletes by allowing trainers and team physicians to make diagnosis in real-time and facilitate faster return to play. PMID- 26271888 TI - Prenatal and childhood polybrominated diphenyl ether (PBDE) exposure and attention and executive function at 9-12 years of age. AB - OBJECTIVE: California children's exposures to polybrominated diphenyl ether flame retardants (PBDEs) are among the highest measured worldwide. We previously reported associations for prenatal and childhood PBDE exposures with decrements in attention, processing speed, fine motor coordination, and cognition in children at ages 5 and 7 years. Here, we investigate associations of PBDEs with attention and executive function at ages 9 to 12 years in the expanded CHAMACOS cohort. METHODS: We measured PBDEs in prenatal and child age 9 year serum samples for families enrolled in the study since pregnancy ("CHAM1", N=321). In a subsequent cohort for which families were enrolled at child age 9 ("CHAM2", N=301), we measured PBDEs in maternal and child samples collected at child age 9, and used predictive modeling to estimate prenatal exposure levels. We examined associations of measured and estimated PBDE concentrations on children's attention and executive functioning at ages 9, 101/2, and 12 years. RESULTS: Geometric means for prenatal and childhood SigmaPBDE levels (sum of PBDE-47, -99, -100, -153) for the expanded CHAMACOS cohort were 26.3 and 63.2 ng/g lipid, respectively, and did not differ significantly between CHAM1 and CHAM2 families. We found consistent associations of prenatal exposure to PBDEs with poorer attention and executive function, measured with parent report and direct neuropsychological testing of the child. For example, using GEE models of repeated outcome measures at ages 9 and 12, a 10-fold increase in prenatal SigmaPBDE was associated with poorer response consistency on the Conners' Continuous Performance Test II (beta=2.9; 95% CI: 0.9, 4.8) and poorer working memory on the Behavioral Rating Inventory of Executive Function (beta=2.5; 95% CI: 0.5, 4.4). Child age 9 SigmaPBDE levels were associated with poorer parent reported attention and executive function for girls but not boys. CONCLUSIONS: Our results suggest that the prefrontal cortex may be a potential target for PBDE exposure and add to a growing literature showing that these ubiquitous toxicants may adversely affect neurodevelopment. PMID- 26271891 TI - On the Bayesness, minimaxity and admissibility of point estimators of allelic frequencies. AB - In this paper, decision theory was used to derive Bayes and minimax decision rules to estimate allelic frequencies and to explore their admissibility. Decision rules with uniformly smallest risk usually do not exist and one approach to solve this problem is to use the Bayes principle and the minimax principle to find decision rules satisfying some general optimality criterion based on their risk functions. Two cases were considered, the simpler case of biallelic loci and the more complex case of multiallelic loci. For each locus, the sampling model was a multinomial distribution and the prior was a Beta (biallelic case) or a Dirichlet (multiallelic case) distribution. Three loss functions were considered: squared error loss (SEL), Kulback-Leibler loss (KLL) and quadratic error loss (QEL). Bayes estimators were derived under these three loss functions and were subsequently used to find minimax estimators using results from decision theory. The Bayes estimators obtained from SEL and KLL turned out to be the same. Under certain conditions, the Bayes estimator derived from QEL led to an admissible minimax estimator (which was also equal to the maximum likelihood estimator). The SEL also allowed finding admissible minimax estimators. Some estimators had uniformly smaller variance than the MLE and under suitable conditions the remaining estimators also satisfied this property. In addition to their statistical properties, the estimators derived here allow variation in allelic frequencies, which is closer to the reality of finite populations exposed to evolutionary forces. PMID- 26271890 TI - Continuum model of T-cell avidity: Understanding autoreactive and regulatory T cell responses in type 1 diabetes. AB - Type 1 diabetes (T1D) is an autoimmune disease that results from the destruction of insulin-secreting pancreatic beta cells, leading to abolition of insulin secretion and onset of diabetes. Cytotoxic CD4(+) and CD8(+) T cells, activated by antigen presenting cells (APCs), are both implicated in disease onset and progression. Regulatory T cells (Tregs), on the other hand, play a leading role in regulating immunological tolerance and resistant homoeostasis in T1D by suppressing effector T cells (Teffs). Recent data indicates that after activation, conventional Teffs transiently produce interleukin IL-2, a cytokine that acts as a growth factor for both Teffs and Tregs. Tregs suppress Teffs through IL-2 deprivation, competition and Teff conversion into inducible Tregs (iTregs). To investigate the interactions of these components during T1D progression, a mathematical model of T-cell dynamics is developed as a predictor of beta-cell loss, with the underlying hypothesis that avidity of Teffs and Tregs, i.e., the binding affinity of T-cell receptors to peptide-major histocompatibility complexes on host cells, is continuum. The model is used to infer a set of criteria that determines susceptibility to T1D in high risk subjects. Our findings show that diabetes onset is guided by the absence of Treg to-Teff dominance at specific high avidities, rather than over the whole range of avidity, and that the lack of overall dominance of Teffs-to-Tregs over time is the underlying cause of the "honeymoon period", the remission phase observed in some T1D patients. The model also suggests that competition between Teffs and Tregs is more effective than Teff-induction into iTregs in suppressing Teffs, and that a prolonged full width at half maximum of IL-2 release is a necessary condition for curbing disease onset. Finally, the model provides a rationale for observing rapid and slow progressors of T1D based on modest heterogeneity in the kinetic parameters. PMID- 26271892 TI - Current Science on Consumer Use of Mobile Health for Cardiovascular Disease Prevention: A Scientific Statement From the American Heart Association. PMID- 26271893 TI - The IL-33/ST2 axis: Role in health and disease. AB - IL-33, an IL-1 family member, is expressed by many cell types and can regulate gene transcription. IL-33 is released upon cell necrosis and the precursor form is enzymatically processed, and then drives inflammation as a damage-associated molecular pattern. The IL-33 receptor ST2, encoded by IL1RL1, is expressed as both a membrane-anchored receptor (ST2L) activated by IL-33, and as a soluble variant (sST2) that exhibits anti-inflammatory properties. The IL-33/ST2 axis is involved in the pathogenesis of atopic and autoimmune diseases, cancer, and central nervous system disorders. Here, we review recent findings on the role of the IL-33/ST2 axis in health and disease. PMID- 26271894 TI - Hydrogen-rich water attenuates amyloid beta-induced cytotoxicity through upregulation of Sirt1-FoxO3a by stimulation of AMP-activated protein kinase in SK N-MC cells. AB - Amyloid beta (Abeta) peptides are identified in cause of neurodegenerative diseases such as Alzheimer's disease (AD). Previous evidence suggests Abeta induced neurotoxicity is linked to the stimulation of reactive oxygen species (ROS) production. The accumulation of Abeta-induced ROS leads to increased mitochondrial dysfunction and triggers apoptotic cell death. This suggests antioxidant therapies may be beneficial for preventing ROS-related diseases such as AD. Recently, hydrogen-rich water (HRW) has been proven effective in treating oxidative stress-induced disorders because of its ROS-scavenging abilities. However, the precise molecular mechanisms whereby HRW prevents neuronal death are still unclear. In the present study, we evaluated the putative pathways by which HRW protects against Abeta-induced cytotoxicity. Our results indicated that HRW directly counteracts oxidative damage by neutralizing excessive ROS, leading to the alleviation of Abeta-induced cell death. In addition, HRW also stimulated AMP activated protein kinase (AMPK) in a sirtuin 1 (Sirt1)-dependent pathway, which upregulates forkhead box protein O3a (FoxO3a) downstream antioxidant response and diminishes Abeta-induced mitochondrial potential loss and oxidative stress. Taken together, our findings suggest that HRW may have potential therapeutic value to inhibit Abeta-induced neurotoxicity. PMID- 26271895 TI - Wif1 and Ifitm3 gene expression preferentially altered in the colon mucosa of benzo[a]pyrene pre-treated mice following exposure to dextran sulfate sodium. AB - Benzo[a]pyrene (BP) is highly mutagenic and yet does not lead to tumor development in the murine colon. We recently reported the generation of colonic tumors one week after treatment with BP followed by dextran sulfate sodium (DSS), a colitis-inducer. In this BP/DSS model, male CD2F1 mice were treated orally with BP at 125 mg/kg/day for 5 days, followed by 4% DSS in drinking water for one week. There has been no report so far on the molecular mechanisms involved in tumor development in this model. In the present study, we performed global gene expression analysis on the colonic mucosae obtained from BP-exposed mice one week after treatment with DSS and those treated with the vehicle, BP, or DSS alone. Global gene expression analysis revealed that there were 563 genes preferentially altered (>=2-fold vs vehicle group) in the colonic mucosae exposed to both BP and DSS. Furthermore, comparative gene expression analysis combined with Ingenuity Pathway AnalysisTM identified 2 genes associated with Wnt/beta-catenin signaling pathway that were preferentially up-regulated (>=2-fold vs vehicle group) when BP and DSS were treated in combination in the distal part (site of predilection for tumor induction) of the colonic mucosae, especially in colonic tumors: WNT inhibitory factor 1 (Wif1; 14.6-fold increase) and interferon induced membrane protein 3 (Ifitm3; 5.7-fold increase). In colonic tumors, expression of Wif1 and Ifitm3 proteins were both confirmed by western blot analysis. These findings suggest that these genes are associated with rapid induction of colonic tumors in mice after exposure to BP/DSS, providing insights into the mechanisms of the BP/DSS short-term colon carcinogenesis. PMID- 26271896 TI - delta-Amyrone inhibits lipopolysaccharide-induced inflammatory cytokines and protects against endotoxic shock in mice. AB - delta-Amyrone (13(18)-Oleanen-3-one), which is an active constituent extracted and separated from Sedum lineare Thunb., has been found to possess a potent anti inflammatory effect in different inflammation model animals. But its effects on lipopolysaccharide (LPS)-induced endotoxic shock have not been previous explored. The aim of this study is to evaluate the effect of delta-Amyrone on LPS-induced inflammatory cytokines and the protective effect on endotoxic shock mice. Experimental animals received delta-amyrone (4 and 8 mg/kg, i.p.) and dexamethasone (DEX) (5 mg/kg, i.p.) at 24 and 1 h before LPS injection. delta Amyrone treatment significantly decreased mortality rate, tissues myeloperoxodase (MPO) activity, p65 NF-kappaB protein expression when compared with the LPS groups. The levels of tumor nectosis factor-alphagene (TNF-alpha) and interleukin 6 (IL-6) both in serum and lung, liver, kidney tissues, as well as the accumulation of nitric oxide (NO) in serum were decreased by delta-amyrone in response to p65 nuclear factors-kappa B (NF-kappaB). These results suggest that the protective activity of delta-amyrone on LPS-induced endotoxic shock is attributed to reducing NO production and mediating the pro-inflammatory cytokines, inhibited NF-kappaB expression. PMID- 26271897 TI - Epidemiology of Human Herpes Virus 8 in Pregnant Women and their Newborns--A cross-sectional delivery survey in Central Gabon. AB - OBJECTIVES: On the background of a high prevalence of HHV-8 infection in pre pubertal Central African children, this study investigated the potential for in utero transmission of HHV-8. PATIENTS: Gabonese pregnant women were invited to provide peripheral and cord blood samples for serological and PCR diagnostics of HHV-8 infection at delivery for this cross-sectional survey. RESULTS: Out of 344 participants 120 (35%, 95% CI: 30-40%) were serologically positive for HHV-8. 31% (95% CI: 22-40%) of cord blood samples of seropositive women had detectable IgG antibodies. Among all seropositive participants HHV-8 was detected by PCR in one maternal peripheral blood sample at delivery (1%, 95% CI: 0.2-7%) and in none of cord blood samples. There was no association between demographic characteristics and infection status. Similarly, there was no difference in risk for premature delivery, low birth weight, and maternal anaemia in HHV-8 seropositive women. DISCUSSION: These data suggest a high seroprevalence of HHV-8 infection in pregnant women, however viraemia at delivery does not commonly occur in Central Africa. Based on these observations it may be speculated that infection of children may occur more commonly either antepartum or later on in infancy and childhood. PMID- 26271898 TI - Serum IP-10 in the diagnosis of latent and active tuberculosis. PMID- 26271899 TI - Hybrid quantum gates between flying photon and diamond nitrogen-vacancy centers assisted by optical microcavities. AB - Hybrid quantum gates hold great promise for quantum information processing since they preserve the advantages of different quantum systems. Here we present compact quantum circuits to deterministically implement controlled-NOT, Toffoli, and Fredkin gates between a flying photon qubit and diamond nitrogen-vacancy (NV) centers assisted by microcavities. The target qubits of these universal quantum gates are encoded on the spins of the electrons associated with the diamond NV centers and they have long coherence time for storing information, and the control qubit is encoded on the polarizations of the flying photon and can be easily manipulated. Our quantum circuits are compact, economic, and simple. Moreover, they do not require additional qubits. The complexity of our schemes for universal three-qubit gates is much reduced, compared to the synthesis with two-qubit entangling gates. These schemes have high fidelities and efficiencies, and they are feasible in experiment. PMID- 26271900 TI - Absorption-induced scattering and surface plasmon out-coupling from absorber coated plasmonic metasurfaces. AB - Interactions between absorbers and plasmonic metasurfaces can give rise to unique optical properties not present for either of the individual materials and can influence the performance of a host of optical sensing and thin-film optoelectronic applications. Here we identify three distinct mode types of absorber-coated plasmonic metasurfaces: localized and propagating surface plasmons and a previously unidentified optical mode type called absorption induced scattering. The extinction of the latter mode type can be tuned by controlling the morphology of the absorber coating and the spectral overlap of the absorber with the plasmonic modes. Furthermore, we show that surface plasmons are backscattered when the crystallinity of the absorber is low but are absorbed for more crystalline absorber coatings. This work furthers our understanding of light-matter interactions between absorbers and surface plasmons to enable practical optoelectronic applications of metasurfaces. PMID- 26271902 TI - Feline lungworms unlock a novel mode of parasite transmission. AB - Snail-borne lungworms exert an enormous toll on the health and welfare of animals and humans. Of these parasites, Aelurostrongylus abstrusus and Troglostrongylus brevior affect the respiratory tract of felids. These lungworms share both the ecological niche and the species of snail (Helix aspersa) acting as intermediate host. Recently, the ability of H. aspersa to shed infective third-stage larvae (L3s) of A. abstrusus and T. brevior in the environment has been demonstrated, matching previous knowledge of mode of transmission of zoonotic lungworms. Here, we evaluated, for the first time, the ability of A. abstrusus and T. brevior L3s to infect new, susceptible snail hosts following their release from experimentally infected molluscs, and refer to this novel route of parasite transmission as intermediesis. The implications of snail-to-snail transmission in the epidemiology of snail-borne diseases are also discussed. PMID- 26271903 TI - Corrigendum: Cell migration and antigen capture are antagonistic processes coupled by myosin II in dendritic cells. PMID- 26271901 TI - Social class based on occupation is associated with hospitalization for A(H1N1)pdm09 infection. Comparison between hospitalized and ambulatory cases. AB - This study aimed to analyse the existence of an association between social class (categorized by type of occupation) and the occurrence of A(H1N1)pmd09 infection and hospitalization for two seasons (2009-2010 and 2010-2011). This multicentre study compared ambulatory A(H1N1)pmd09 confirmed cases with ambulatory controls to measure risk of infection, and with hospitalized A(H1N1)pmd09 confirmed cases to asses hospitalization risk. Study variables were: age, marital status, tobacco and alcohol use, pregnancy, chronic obstructive pulmonary disease, chronic respiratory failure, cardiovascular disease, diabetes, chronic liver disease, body mass index >40, systemic corticosteroid treatment and influenza vaccination status. Occupation was registered literally and coded into manual and non-manual worker occupational social class groups. A conditional logistic regression analysis was performed. There were 720 hospitalized cases, 996 ambulatory cases and 1062 ambulatory controls included in the study. No relationship between occupational social class and A(H1N1)pmd09 infection was found [adjusted odds ratio (aOR) 0.97, 95% confidence interval (CI) 0.74-1.27], but an association (aOR 1.53, 95% CI 1.01-2.31) between occupational class and hospitalization for A(H1N1)pmd09 was observed. Influenza vaccination was a protective factor for A(H1N1)pmd09 infection (aOR 0.41, 95% CI 0.23-0.73) but not for hospitalization. We conclude that manual workers have the highest risk of hospitalization when infected by influenza than other occupations but they do not have a different probability of being infected by influenza. PMID- 26271905 TI - Ten situations in which ECMO is unlikely to be successful. PMID- 26271904 TI - Improved human visuomotor performance and pupil constriction after choline supplementation in a placebo-controlled double-blind study. AB - Only few nutrients are known to enhance cognition. Here we explore whether visuomotor performance can be improved through the intake of the nutrient choline, an essential chemical compound in a vertebrate's diet. Choline is abundant in for example eggs and shrimps and many animal studies suggest that it serves as a cognitive enhancer. As choline is important for the communication between motor neurons and the control of skeletal muscles, we assumed that choline supplementation may have positive effects on action coordination in humans. A group of twenty-eight individuals ingested two grams of choline bitartrate or a placebo in two separate sessions. Seventy minutes post ingestion, participants performed a visuomotor aiming task in which they had to rapidly hit the centers of targets. Results showed that participants hit targets more centrally after choline supplementation. Pupil size (a cognition-sensitive biomarker) also significantly decreased after choline intake and correlated positively with the hit distance to the targets and the number of target misses, and negatively with reaction times. These findings point to a choline-induced bias towards action precision in the trade-off between speed and accuracy. The changes in pupil size suggest that choline uptake alters cholinergic functions in the nervous system. PMID- 26271906 TI - 'I just have admitted an interesting sepsis'. Do we dehumanize our patients? PMID- 26271907 TI - Low-dose heparin during extracorporeal membrane oxygenation treatment in adults. PMID- 26271908 TI - What's new in myocarditis? PMID- 26271909 TI - Understanding stress cardiomyopathy. PMID- 26271910 TI - Activity and stability trends of perovskite oxides for oxygen evolution catalysis at neutral pH. AB - Perovskite oxides (ABO3) have been studied extensively to promote the kinetics of the oxygen evolution reaction (OER) in alkaline electrolytes. However, developing highly active catalysts for OER at near-neutral pH is desirable for many photoelectrochemical/electrochemical devices. In this paper, we systematically studied the activity and stability of well-known perovskite oxides for OER at pH 7. Previous activity descriptors established for perovskite oxides at pH 13, such as having an eg occupancy close to unity or having an O p-band center close to Fermi level, were shown to scale with OER activity at pH 7. Stability was a greater challenge at pH 7 than at pH 13, where two different modes of instability were identified from combined transmission electron microscopy and density functional theory analyses. Perovskites with O p-band close to Fermi level showed leaching of A-site atoms and surface amorphization under all overpotentials examined at pH 7, while those with O p-band far from Fermi level were stable under low OER current/potential but became unstable at high current/potential accompanied by leaching of B-site atoms. Therefore, efforts are needed to enhance the activity and stability of perovskites against A-site or B-site loss if used at neutral pH. PMID- 26271911 TI - [Visceral pain]. AB - Chronic visceral pain is an unresolved neurobiological, medical and socioeconomic challenge. Up to 20% of the adult population suffer from chronic visceral pain and abdominal complaints constitute a prevalent symptom also in children and adolescents. Existing treatment approaches are often unsuccessful and patients typically suffer from multiple somatic and psychological symptoms. This complex situation requires integrative treatment approaches. This review summarizes current basic and clinical research on acute and chronic visceral pain with a focus on research groups in Germany. Despite significant clinical and scientific advances, a number of questions remain open calling for more funding to support research to elucidate the complex pathophysiology of chronic visceral pain and to develop and test new treatment approaches. Research support should focus on interdisciplinary concepts and methodology using expertise from multiple disciplines. The field would also benefit from a broader integration of visceral pain into teaching curricula in medicine and psychology and should aim to motivate young clinicians and scientists to strive for a career within this important and highly fascinating area. PMID- 26271912 TI - [Multimodal pain therapy. Current situation]. AB - A multidisciplinary approach for the management of patients with chronic pain is now well-established in many countries, especially in situations involving a complex disease process in the sense of a biopsychosocial model. Both the efficacy and cost-effectiveness of multidisciplinary pain treatment programs and their superiority compared to unimodal therapy has been documented in a number of studies, reviews and meta-analyses, in particular for patients suffering from chronic low back pain. Nevertheless, there are still major shortcomings concerning the definition of multimodal and multidisciplinary treatment and the quality of structures and processes, compared for example to the standards defined by the German Pain Society (Deutsche Schmerzgesellschaft). Furthermore, there is still no consensus on specific therapeutic approaches, the differentiation between responders and non-responders as well as on the tools required for measurement. All these questions will have to be answered by concerted efforts in a multicenter setting. PMID- 26271914 TI - How Portuguese and American teachers plan for literacy instruction. AB - This study explored American and Portuguese elementary teachers' preferences in planning for literacy instruction using the Language Arts Activity Grid (LAAG; Cunningham, Zibulsky, Stanovich, & Stanovich, 2009), on which teachers described their preferred instructional activities for a hypothetical 2-h language arts block. Portuguese teachers (N = 186) completed Portuguese versions of a background questionnaire and LAAG electronically, in Survey Monkey; American teachers (N = 102) completed identical English measures using paper and pencil. Results showed that teachers in both groups usually addressed comprehension and reading fluency on their LAAGs and that they also allocated the most time to these two areas. However, American teachers were more likely to include teacher directed fluency activities, whereas Portuguese teachers were more likely to include fluency activities that were not teacher directed. Significantly more American than Portuguese teachers addressed phonics in their planning, whereas significantly more Portuguese than American teachers addressed writing processes such as revision. Both groups of educators demonstrated large variability in planning, with many teachers omitting important components of literacy identified by researchers, for writing as well as reading. The study highlights the importance of providing teachers with comprehensive, research-based core literacy curricula as well as professional development on key components of literacy. Study findings also suggest significant relationships between orthographic transparency and teachers' instructional planning. PMID- 26271913 TI - Iron ore pollution in Mandovi and Zuari estuarine sediments and its fate after mining ban. AB - Iron ore was mined from the banded iron formations of Goa, India, and transported through the Mandovi and Zuari estuaries for six decades until the ban on mining from September 2012. Here we focus on the environmental magnetic properties of sediments from the catchment area, upstream and downstream of these estuaries, and adjacent shelf during peak mining time. Magnetic susceptibility (chi lf) and saturation isothermal remanent magnetization (SIRM) values of sediments were highest in upstream (catchment area and estuaries), decreased gradually towards downstream (catchment area and estuaries), and were lowest on the adjacent shelf. The chi lf values of the Mandovi estuary were two to fourfold higher than those in the Zuari. The sediments of these two estuaries after the mining ban showed enrichment of older magnetite and sharp decrease in the SIRM values. Although the input of ore material has been reduced after mining ban, more flushing of estuarine sediments is required for healthier environment. PMID- 26271916 TI - Reading under the skin: physiological activation during reading in children with dyslexia and typical readers. AB - The aim of this study was to investigate physiological activation during reading and control tasks in children with dyslexia and typical readers. Skin conductance response (SCR) recorded during four tasks involving reading aloud, reading silently, and describing illustrated stories aloud and silently was compared for children with dyslexia (n = 16) and a control group of typical readers (n = 16). Children's school wellness was measured through self- and parent-proxy reports. Significantly lower SCR was found for dyslexic children in the reading-aloud task, compared to the control group, whereas all participants showed similar physiological reactions to the other experimental conditions. SCR registered during reading tasks correlated with "Child's emotional difficulties," as reported by parents. Possible interpretations of the lower activation during reading aloud in dyslexic children are discussed. PMID- 26271915 TI - Enhancing the metalinguistic abilities of pre-service teachers via coursework targeting language structure knowledge. AB - Low metalinguistic knowledge of pre-service and in-service teachers is likely to restrict the provision of evidence-based literacy instruction in the classroom. Despite such concerns, relatively few studies have examined the effects of teacher preparation coursework in building pre-service teachers' language structure knowledge. This study examined the effects of 7 h of language structure coursework, delivered over 7 weeks, on 121 New Zealand pre-service teachers in their initial year of study. Changes in participants' phonological awareness, morphological awareness, and orthographic knowledge were tracked across the teaching period. The impact of the coursework for participants who presented with strong spelling (n = 24) and poor spelling (n = 24) ability was also compared. The cohort demonstrated significant gains across all measures. Strong spellers responded more favourably to the teaching than poor spellers, even when accounting for initial levels of meta-linguistic knowledge. Implications for the development of teacher preparation programmes that enhance the provision of effective literacy instruction are discussed. PMID- 26271917 TI - Situational variations in ethnic identity across immigration generations: Implications for acculturative change and cross-cultural adaptation. AB - This study examined whether the acculturation of ethnic identity is first evident in more public situations with greater opportunity for intercultural interaction and eventually penetrates more intimate situations. It also investigated whether situational variations in identity are associated with cross-cultural adaptation. First-generation (G1), second-generation (G2) and mixed-parentage second generation (G2.5) young adult Canadians (n = 137, n = 169, and n = 91, respectively) completed a questionnaire assessing their heritage and Canadian identities across four situational domains (family, friends, university and community), global heritage identity and cross-cultural adaptation. Consistent with the acculturation penetration hypothesis, the results showed Canadian identity was stronger than heritage identity in public domains, but the converse was true in the family domain; moreover, the difference between the identities in the family domain was attenuated in later generations. Situational variability indicated better adaptation for the G1 cohort, but poorer adaptation for the G2.5 cohort. For the G2 cohort, facets of global identity moderated the relation, such that those with a weaker global identity experienced greater difficulties and hassles with greater identity variability but those with a stronger identity did not. These results are interpreted in light of potential interpersonal issues implied by situational variation for each generation cohort. PMID- 26271918 TI - Uncertainty in the Bayesian meta-analysis of normally distributed surrogate endpoints. AB - We investigate the effect of the choice of parameterisation of meta-analytic models and related uncertainty on the validation of surrogate endpoints. Different meta-analytical approaches take into account different levels of uncertainty which may impact on the accuracy of the predictions of treatment effect on the target outcome from the treatment effect on a surrogate endpoint obtained from these models. A range of Bayesian as well as frequentist meta analytical methods are implemented using illustrative examples in relapsing remitting multiple sclerosis, where the treatment effect on disability worsening is the primary outcome of interest in healthcare evaluation, while the effect on relapse rate is considered as a potential surrogate to the effect on disability progression, and in gastric cancer, where the disease-free survival has been shown to be a good surrogate endpoint to the overall survival. Sensitivity analysis was carried out to assess the impact of distributional assumptions on the predictions. Also, sensitivity to modelling assumptions and performance of the models were investigated by simulation. Although different methods can predict mean true outcome almost equally well, inclusion of uncertainty around all relevant parameters of the model may lead to less certain and hence more conservative predictions. When investigating endpoints as candidate surrogate outcomes, a careful choice of the meta-analytical approach has to be made. Models underestimating the uncertainty of available evidence may lead to overoptimistic predictions which can then have an effect on decisions made based on such predictions. PMID- 26271919 TI - Are reductions in emergency department length of stay associated with improvements in quality of care? A difference-in-differences analysis. AB - BACKGROUND: We sought to determine whether patients seen in hospitals who had reduced overall emergency department (ED) length of stay (LOS) in the 2 years following the introduction of the Ontario Emergency Room Wait Time Strategy were more likely to experience improvements in other measures of ED quality of care for three important conditions. METHODS: Retrospective medical record review using difference-in-differences analysis to compare changes in performance on quality indicators over the 3-year period between 11 Ontario hospitals where the median ED LOS had improved from fiscal year 2008 to 2010 and 13 matched sites where ED LOS was unchanged or worsened. Patients with acute myocardial infarction (AMI), asthma and paediatric and adult upper limb fractures in these hospitals in 2008 and 2010 were evaluated with respect to 18 quality indicators reflecting timeliness and safety/effectiveness of care in the ED. In a secondary analysis, we examined shift-level ED crowding at the time of the patient visit and performance on the quality indicators. RESULTS: Median ED LOS improved by up to 26% (63 min) from 2008 to 2010 in the improved hospitals, and worsened by up to 47% (91 min) in the unimproved sites. We abstracted 4319 and 4498 charts from improved and unimproved hospitals, respectively. Improvement in a hospital's overall median ED LOS from 2008 to 2010 was not associated with a change in any of the other ED quality indicators over the same time period. In our secondary analysis, shift-level crowding was associated only with indicators that reflected timeliness of care. During less crowded shifts, patients with AMI were more likely to be reperfused within target intervals (rate ratio 1.59, 95% CI 1.03 to 2.45), patients with asthma more often received timely administration of steroids (rate ratio 1.88, 95% CI 1.59 to 2.24) and beta-agonists (rate ratio 1.47, 95% CI 1.25 to 1.74), and adult (but not paediatric) patients with fracture were more likely to receive analgesia or splinting within an hour (rate ratio 1.66, 95% CI 1.22 to 2.26). CONCLUSIONS: These results suggest that a policy approach that targets only reductions in ED LOS is not associated with broader improvements in selected quality measures. At the same time, there is no evidence that efforts to address crowding have a detrimental effect on quality of care. PMID- 26271920 TI - What happens when healthcare innovations collide? PMID- 26271922 TI - Theoretical Study of alpha-V2O5 -Based Double-Wall Nanotubes. AB - First-principles calculations of the atomic and electronic structure of double wall nanotubes (DWNTs) of alpha-V2 O5 are performed. Relaxation of the DWNT structure leads to the formation of two types of local regions: 1) bulk-type regions and 2) puckering regions. Calculated total density of states (DOS) of DWNTs considerably differ from that of single-wall nanotubes and the single layer, as well as from the DOS of the bulk and double layer. Small shoulders that appear on edges of valence and conduction bands result in a considerable decrease in the band gaps of the DWNTs (up to 1 eV relative to the single-layer gaps). The main reason for this effect is the shift of the inner- and outer-wall DOS in opposite directions on the energetic scale. The electron density corresponding to shoulders at the conduction-band edges is localized on vanadium atoms of the bulk type regions, whereas the electron density corresponding to shoulders at the valence-band edges belongs to oxygen atoms of both regions. PMID- 26271921 TI - Unravelling the patterns of host immune responses in Plasmodium vivax malaria and dengue co-infection. AB - BACKGROUND: Concurrent malaria and dengue infection is frequently diagnosed in endemic countries, but its immunopathology remains largely unknown. In the present study, a large panel of cytokines/chemokines and clinical laboratory markers were measured in patients with Plasmodium vivax and dengue co-infection as well as in individuals with malaria or dengue mono-infections in order to identify biosignatures of each clinical condition. METHODS: Individuals from the Brazilian Amazon were recruited between 2009 and 2013 and classified in three groups: vivax malaria (n = 52), dengue (n = 30) and vivax malaria and dengue co infection (n = 30). P. vivax malaria was diagnosed by thick blood smear and confirmed by PCR; dengue cases were detected by IgM ELISA or NS1 protein. The plasma levels of cytokines and chemokines were determined by multiplex assay. RESULTS: Individuals with malaria and dengue co-infection displayed lower levels of platelets and haemoglobin than those with malaria or dengue mono-infections (p = 0.0047 and p = 0.0001, respectively). The group of individuals co-infected exhibited the highest median concentrations of IFN-gamma, IL-6, CCL4 than the mono-infected groups. Network analyses of plasma cytokines/chemokines revealed that malaria and dengue co-infection exhibits a distinct immune profile with critical roles for TNF, IL-6 and IFN-gamma. Further, parasitaemia levels displayed positive significant interactions with IL-6, CCL4 and IL-10 in the group of patients co-infected with malaria and dengue. No differences were observed in distribution of dengue virus serotypes and Plasmodium parasitaemia levels between the groups. CONCLUSIONS: The findings described here identify unique patterns of circulating immunological markers in cases of malaria and dengue co-infection and provide insights on the immunopathology of this co-morbid condition. PMID- 26271923 TI - Comparison of the performance of zotarolimus- and everolimus-eluting stents by optical coherence tomography and coronary angioscopy. AB - Overall stent performance should be characterized by geometric luminal gain acquisition, neointimal coverage of the stent struts, and stabilization of the underlying inflammatory neoatheroma. The aim of this study was to compare the performance of zotarolimus-eluting stent (ZES), everolimus-eluting stent (EES) and bare metal stent (BMS) using optical coherence tomography (OCT) and coronary angioscopy. For 36 stented coronary lesions (BMS, 12 lesions; ZES, 11 lesions; EES, 13 lesions) in 27 patients, we calculated neointimal area and uncovered stent strut rate based on OCT findings at 10 months after stent placement. The grades of neointimal coverage and yellow color, both of which were classified from 0 to 3, were also assessed by coronary angioscopy. The plaque area of the ZES lesions was larger than that of the EES lesions (P < 0.05) but smaller than that of the BMS lesions (P < 0.05). The OCT-based uncovered rate of the ZES lesions was less than that of the EES lesions (P < 0.01), but similar to that of the BMS lesions. The stent coverage grade by angioscopy was higher in the ZES lesions than in the EES lesions (P < 0.05), but similar to the BMS lesions. The yellow grade was less in the ZES lesions than in the EES lesions (P < 0.01), but similar to the BMS lesions. ZES might be better than BMS in terms of neointimal thickening, and better than EES in terms of neointimal coverage as well as prevention of neoatheroma formation. ZES may have superior performance compared with EES. PMID- 26271924 TI - Comparison of predicted pesticide concentrations in groundwater from SCI-GROW and PRZM-GW models with historical monitoring data. AB - BACKGROUND: A key factor in the human health risk assessment process for the registration of pesticides by the US Environmental Protection Agency (EPA) is an estimate of pesticide concentrations in groundwater used for drinking water. From 1997 to 2011, these estimates were obtained from the EPA empirical model SCI GROW. Since 2012, these estimates have been obtained from the EPA deterministic model PRZM-GW, which has resulted in a significant increase in estimated groundwater concentrations for many pesticides. RESULTS: Historical groundwater monitoring data from the National Ambient Water Quality Assessment (NAWQA) Program (1991-2014) were compared with predicted groundwater concentrations from both SCI-GROW (v.2.3) and PRZM-GW (v.1.07) for 66 different pesticides of varying environmental fate properties. The pesticide environmental fate parameters associated with over- and underprediction of groundwater concentrations by the two models were evaluated. CONCLUSION: In general, SCI-GROW2.3 predicted groundwater concentrations were close to maximum historically observed groundwater concentrations. However, for pesticides with soil organic carbon content values below 1000 L kg(-1) and no simulated hydrolysis, PRZM-GW overpredicted, often by greater than 100 ppb. (c) 2015 Society of Chemical Industry. PMID- 26271926 TI - Identification of components of health complexity on internal medicine units by means of the INTERMED method. AB - BACKGROUND: The INTERMED was developed for the early identification of biological, psychological, social and health system factors considered interacting in health complexity. This is defined as the interference with the achievement of expected or desired health and service use outcomes when patients are exposed to standard care. OBJECTIVE: The aim of this study was to test the INTERMED's ability to identify 'case' and 'care' complexity, identifying patients that would especially benefit from integrated care. METHODS: Observational longitudinal study of Internal medicine in patients in two National Health System hospitals in Spain using the INTERMED (patients scoring >= 21 were considered to be 'complex'); the Cumulative Illness Rating Scale (CIRS), a severity of illness assessment; and standard clinical variables. RESULTS: Six hundred and fifteen consecutives were included, and the prevalence of health complexity was 27.6%. The greatest differences between patients with and without health complexity were observed in the non-biological domains. Eighty-five per cent of patients with health complexity had non-biological items considered to require timely (immediately or soon) assistance or intervention compared to 30% of those without, nearly a threefold difference. Complex patients had a significantly higher number of medical diagnoses (p = 0.002) and number of psychiatric referrals (p = 0.041), but there were no differences in CIRS scores or lengths of stay. CONCLUSION: The INTERMED has the potential to identify a considerable subset of complex internal medicine inpatients for which timely corrective action related to non-biological risk factors not typically uncovered during standard medical evaluations would be considered beneficial. PMID- 26271925 TI - Distinct polymer physics principles govern chromatin dynamics in mouse and Drosophila topological domains. AB - BACKGROUND: In higher eukaryotes, the genome is partitioned into large "Topologically Associating Domains" (TADs) in which the chromatin displays favoured long-range contacts. While a crumpled/fractal globule organization has received experimental supports at higher-order levels, the organization principles that govern chromatin dynamics within these TADs remain unclear. Using simple polymer models, we previously showed that, in mouse liver cells, gene-rich domains tend to adopt a statistical helix shape when no significant locus specific interaction takes place. RESULTS: Here, we use data from diverse 3C derived methods to explore chromatin dynamics within mouse and Drosophila TADs. In mouse Embryonic Stem Cells (mESC), that possess large TADs (median size of 840 kb), we show that the statistical helix model, but not globule models, is relevant not only in gene-rich TADs, but also in gene-poor and gene-desert TADs. Interestingly, this statistical helix organization is considerably relaxed in mESC compared to liver cells, indicating that the impact of the constraints responsible for this organization is weaker in pluripotent cells. Finally, depletion of histone H1 in mESC alters local chromatin flexibility but not the statistical helix organization. In Drosophila, which possesses TADs of smaller sizes (median size of 70 kb), we show that, while chromatin compaction and flexibility are finely tuned according to the epigenetic landscape, chromatin dynamics within TADs is generally compatible with an unconstrained polymer configuration. CONCLUSIONS: Models issued from polymer physics can accurately describe the organization principles governing chromatin dynamics in both mouse and Drosophila TADs. However, constraints applied on this dynamics within mammalian TADs have a peculiar impact resulting in a statistical helix organization. PMID- 26271927 TI - Pleural sarcoidosis diagnosed on the basis of an increased CD4/CD8 lymphocyte ratio in pleural effusion fluid: a case report. AB - INTRODUCTION: Pleural effusion induced by sarcoidosis is rare, and pleural sarcoidosis is often diagnosed by thoracoscopic surgery. The diagnosis of pleural sarcoidosis using thoracentesis may be less invasive when sarcoidosis is already diagnosed histologically in more than one organ specimen. Here we report the case of a 64-year-old woman with pleural sarcoidosis diagnosed on the basis of an increased CD4/CD8 lymphocyte ratio in pleural effusion fluid obtained by thoracentesis. This case report is important because it highlights the usefulness of the CD4/CD8 lymphocyte ratio in pleural effusion as an indicator of pleural involvement of sarcoidosis. CASE PRESENTATION: A 64-year-old Japanese woman visited our hospital with an initial symptom of dyspnea on exertion for a period of 4 months. Chest computed tomography showed bilateral hilar and multiple mediastinal lymphadenopathy, multiple small nodular shadows in her bilateral lungs, small nodular shadows along the interlobar pleura, and bilateral pleural effusion. Her serum angiotensin-converting enzyme and soluble interleukin-2 receptor levels were elevated. Histological analysis of a resected subcutaneous nodule, and biopsy specimens from a right mediastinal lymph node and from her right lung revealed non-caseous epithelioid granulomas. Her bronchoalveolar lavage fluid exhibited a predominance of lymphocytes together with an increase in the CD4/CD8 lymphocyte ratio. The lymphocytic predominance and the increased CD4/CD8 lymphocyte ratio were also detected in the right-sided pleural effusion fluid obtained by thoracentesis. We diagnosed sarcoidosis with pleural involvement. Because pleural effusion did not resolve spontaneously and her symptom of dyspnea on exertion worsened, corticosteroid therapy was initiated, which ameliorated the sarcoidosis and the pleuritis. CONCLUSIONS: Analysis of the CD4/CD8 lymphocyte ratio in pleural effusion fluid obtained by thoracentesis may be helpful for the diagnosis of pleural sarcoidosis when the diagnosis is already made by histological examination of more than one organ specimen. PMID- 26271928 TI - Reducing electronic media use in 2-3 year-old children: feasibility and efficacy of the Family@play pilot randomised controlled trial. AB - BACKGROUND: Participation in electronic media use among 2-3 year olds is high and associated with adverse health and developmental outcomes. This study sought to test the feasibility and potential efficacy of a family-based program to decrease electronic media (EM) use in 2-3-year-old children. METHODS: Family@play was a six-session pilot randomised controlled trial delivered to parents of 2-3 year old children from August to September 2012 in a community environment in the Illawarra region of New South Wales, Australia. Development of program content was guided by Social Cognitive and Family Systems Theories. The primary outcome was children's electronic media use. Secondary outcomes included children's time in sitting, standing and stepping. Data collectors were blinded to group allocation. Parents completed comprehensive process evaluation measures and participated in focus group discussions following completion of the program. Regression analyses were undertaken and effect sizes calculated using principles of intention to treat. RESULTS: Twenty-two participants (n = 12 intervention; n = 10 control) provided complete baseline data; complete data from 16 participants (n = 6 intervention; n = 10 control) were available post-intervention. Process evaluation results were high, showing the acceptability of the program. Compared with children in the control group, there were greater decreases in total EM use among children in the intervention group (adjusted difference [95 % CI] = -31.2 mins/day [-71.0-8.6] Cohen's d = 0.70). Differences for other outcomes were in the hypothesised direction and ranged from small for postural (sitting, standing, stepping) outcomes to moderate to large for individual electronic media (e.g. TV viewing, DVD/video viewing). CONCLUSIONS: This is the first family-based study to engage families of 2-3 year old children outside the United States and target multiple EM behaviours. Family@play was shown to be a feasible and acceptable intervention to deliver to families of 2-3 year old children. Potential efficacy is evident from moderate to large effect sizes. A larger trial is warranted to test the efficacy of the program. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12612000470897 ). PMID- 26271929 TI - Hemodynamic monitoring using a single-use indwelling transesophageal echocardiography probe in an unstable patient after open-heart surgery. AB - BACKGROUND: Hemodynamic monitoring is frequently needed in ventilated patients with unstable hemodynamics after open-heart surgery. Novel miniaturized single use transesophageal echocardiographic probe has been scarcely used in this clinical setting. CASE PRESENTATION: A patient who underwent a scheduled open heart surgery developed a ventilator-associated pneumonia and was referred to the intensive care unit for post-operative acute respiratory distress syndrome. Hemodynamic monitoring was performed with a single-use indwelling transesophageal echocardiography probe during 50 h. Initially, a contrast study depicted a patent foramen ovale with a right-to-left shunt. Nitric oxide was administered and positive end-expiration pressure was reduced. Subsequently, the patient became hemodynamically unstable and the identification of a localized tamponade due to compressive left atrial hematoma prompted reoperation. CONCLUSIONS: The novel hemodynamic monitoring device described here appears valuable to help identifying severe post-operative complications and guide acute care. PMID- 26271930 TI - ASSOCIATION STUDY BETWEEN OLIGODENDROCYTE TRANSCRIPTION FACTOR 2 GENE AND OBSESSIVE-COMPULSIVE DISORDER IN A CHINESE HAN POPULATION. AB - BACKGROUND: Oligodendrocyte transcription factor 2 (OLIG2) is primarily concentrated in the brain and spinal cord ventricular zone, where this protein stimulates oligodendrocytes and specific neurons, determines motor neuron and oligodendrocyte differentiation, and sustains replication in early development. Recent studies have demonstrated that OLIG2 gene is associated with mental disorders, such as schizophrenia, mood disorder, and obsessive-compulsive disorder (OCD). METHODS: The aim of the present study was to explore whether OLIG2 gene is associated with OCD in a Chinese Han population through the assessment and analysis of three single nucleotide polymorphisms (SNPs), namely, rs762178, rs1059004, and rs9653711, selected from OLIG2 gene sequences from 400 OCD samples and 459 healthy controls in a case-controlled association study. RESULTS: We demonstrated three principal results. First, SNP rs762178 was associated with OCD, female OCD, and early-onset OCD; rs1059004 was associated with OCD and early-onset OCD; and rs9653711 was also associated with OCD and early-onset OCD. Second, the pairs of loci rs762178 and rs1059004, rs1059004 and rs9653711, and rs762178 and rs9653711 exhibited linkage disequilibrium. Third, the three-locus A-C-G haplotype was associated with early-onset OCD. CONCLUSIONS: The present study is the first to verify the associations of SNPs rs762178, rs1059004, and rs9653711 of the OLIG2 gene with OCD in a Chinese Han population. Thus, OLIG2 might serve as a potential target for OCD treatment in future studies. Further studies should verify the current findings. PMID- 26271931 TI - Strength training improves muscle aerobic capacity and glucose tolerance in elderly. AB - The primary aim of this study was to investigate the effect of short-term resistance training (RET) on mitochondrial protein content and glucose tolerance in elderly. Elderly women and men (age 71 +/- 1, mean +/- SEM) were assigned to a group performing 8 weeks of resistance training (RET, n = 12) or no training (CON, n = 9). The RET group increased in (i) knee extensor strength (concentric +11 +/- 3%, eccentric +8 +/- 3% and static +12 +/- 3%), (ii) initial (0-30 ms) rate of force development (+52 +/- 26%) and (iii) contents of proteins related to signaling of muscle protein synthesis (Akt +69 +/- 20 and mammalian target of rapamycin +69 +/- 32%). Muscle fiber type composition changed to a more oxidative profile in RET with increased amount of type IIa fibers (+26.9 +/- 6.8%) and a trend for decreased amount of type IIx fibers (-16.4 +/- 18.2%, P = 0.068). Mitochondrial proteins (OXPHOS complex II, IV, and citrate synthase) increased in RET by +30 +/- 11%, +99 +/- 31% and +29 +/- 8%, respectively. RET resulted in improved oral glucose tolerance measured as reduced area under curve for glucose (-21 +/- 26%) and reduced plasma glucose 2 h post-glucose intake (-14 +/- 5%). In CON parameters were unchanged or impaired. In conclusion, short-term resistance training in elderly not only improves muscular strength, but results in robust increases in several parameters related to muscle aerobic capacity. PMID- 26271932 TI - The Incident Command System: a literature review. AB - Given the foundational and the fundamental role that the Incident Command System (ICS) is intended to play in on-scene response efforts across the United States, it is important to determine what is known about the system and how this is known. Accordingly, this study addresses the following research question: 'How has research explored the ICS?'. To probe this question, a methodological review of the scant, but widening, pool of research literature directly related to the ICS was conducted. This paper reports on the findings of the analysis related to the focus, theoretical frameworks, population and sampling, methods, results, and conclusions of the existing research literature. While undertaken using different methodological approaches, the ICS research suggests that the system may be limited in its usefulness. In addition, the paper discusses the implications of the research for the state of knowledge of the system and for the direction of future research. PMID- 26271935 TI - Correction: Thymidylate synthase inspired biomodel reagent for the conversion of uracil to thymine. AB - Correction for 'Thymidylate synthase inspired biomodel reagent for the conversion of uracil to thymine' by Palwinder Singh et al., Chem. Commun., 2015, 51, 9961 9964. PMID- 26271936 TI - Effects of walker gender and observer gender on biological motion walking direction discrimination. AB - The ability to recognize the movements of other biological entities, such as whether a person is walking toward you, is essential for survival and social interaction. Previous studies have shown that the visual system is particularly sensitive to approaching biological motion. In this study, we examined whether the gender of walkers and observers influenced the walking direction discrimination of approaching point-light walkers in fine granularity. The observers were presented a walker who walked in different directions and were asked to quickly judge the walking direction (left or right). The results showed that the observers demonstrated worse direction discrimination when the walker was depicted as male than when the walker was depicted as female, probably because the observers tended to perceive the male walkers as walking straight ahead. Intriguingly, male observers performed better than female observers at judging the walking directions of female walkers but not those of male walkers, a result indicating perceptual advantage with evolutionary significance. These findings provide strong evidence that the gender of walkers and observers modulates biological motion perception and that an adaptive perceptual mechanism exists in the visual system to facilitate the survival of social organisms. PMID- 26271934 TI - Both the central and peripheral retina contribute to myopia development in chicks. AB - PURPOSE: This study examined the contribution of the central and peripheral retina to the development of form deprivation myopia in chicks. METHODS: Chicks were treated for 7 days either with centrally form-deprived (CFD) lenses of 2/4/6/8 mm diameter central diffuse zone, or a full size diffuser lens on their right eyes. The left eyes wore a full field plano lens. Axial dimensions and refractions were measured before and after 4 and 7 days of lens wear. RESULTS: All eyes that had worn CFD lenses of 2/4/6/8 mm had significant changes in refractive errors (from -2.69 +/- 0.40 D to -6.13 +/- 0.76 D, p < 0.05), vitreous chamber depth (from 0.19 +/- 0.04 mm to 0.56 +/- 0.04 mm, p < 0.05) and axial length (from 0.42 +/- 0.03 mm to 0.96 +/- 0.04 mm, p < 0.05) during the experiment, except for the changes in refractive error (-2.81 +/- 0.33 D, p = 0.053) and axial length (0.77 +/- 0.04 mm, p = 0.050) in the 2 mm lens group after 7 days of lens wear. The myopic shift in the CFD lens wearing eyes was due primarily to an increase in vitreous chamber depth. Linear regression analysis showed that the changes of refractive error, vitreous chamber depth and axial length were positively correlated with the size of central form-deprived retina. Form depriving the central retina produced axial myopia even in the presence of clear peripheral vision. CONCLUSIONS: The current study showed that both the central and peripheral retina contributes to myopia development in chicks. The amount of myopia induced increased linearly with the area of retina being form deprived. It suggests that in terms of decoding optical input for growth, the area of retina being exposed to optical signals may be critical in determining eye growth. PMID- 26271933 TI - Defining the structural characteristics of annexin V binding to a mimetic apoptotic membrane. AB - Annexin V is of crucial importance for detection of the phosphatidylserine of apoptotic cell membranes. However, the manner in which different amounts of phosphatidylserine at the membrane surface at different stages of apoptosis contribute to binding of annexin V is unclear. We have used a quartz crystal microbalance combined with dissipative monitoring (QCM-D) and neutron reflectivity to characterize binding of human annexin V to supported bilayers of different phospholipid composition. We created model apoptotic bilayers of 1 palmitoyl-2-oleoyl-sn-glycerophosphocholine and 1-palmitoyl-2-oleoyl-sn glycerophosphoserine (POPS) in the ratios 19:1, 9:1, 6.7:1, 4:1, 3:1, and 2:1 (w/w) in the presence of 2.5 mM CaCl2. QCM-D data revealed that annexin V bound less to supported fluid lipid bilayers with higher POPS content (>25 % POPS). Neutron reflectivity was used to further characterize the detailed composition of lipid bilayers with membrane-bound annexin V. Analysis confirmed less annexin V binding with higher POPS content, that bound annexin V formed a discrete layer above the lipid bilayer with little effect on the overall structure of the membrane, and that the thickness and volume fraction of the annexin V layer varied with POPS content. From these results we show that the POPS content of the outer surface of lipid bilayers affects the structure of membrane-bound annexin V. PMID- 26271937 TI - A new research trend in social neuroscience: Towards an interactive-brain neuroscience. AB - The ability to flexibly modulate our behaviors in social contexts and to successfully interact with other persons is a fundamental, but pivotal, requirement for human survival. Although previous social neuroscience research with single individuals has contributed greatly to our understanding of the basic mechanisms underlying social perception and social emotions, much of the dynamic nature of interactions between persons remains beyond the reach of single-brain studies. This has led to a growing argument for a shift to the simultaneous measurement of the brain activity of two or more individuals in realistic social interactions-an approach termed "hyperscanning." Although this approach offers important promise in unlocking the brain's role in truly social situations, there are multiple procedural and theoretical questions that require review and analysis. In this paper we discuss this research trend from four aspects: hyperscanning apparatus, experimental task, quantification method, and theoretical interpretation. We also give four suggestions for future research: (a) electroencephalography and near-infrared spectroscopy are useful tools by which to explore the interactive brain in more ecological settings; (b) games are an appropriate method to simulate daily life interactions; (c) transfer entropy may be an important method by which to quantify directed exchange of information between brains; and (d) more explanation is needed of the results of interbrain synchronization itself. PMID- 26271938 TI - Mineralocorticoid receptors in the ventral hippocampus are involved in extinction memory in rats. AB - Fear extinction decreases conditioned fear responses that normally occur when a conditioned stimulus (CS) is repeatedly presented in the absence of an aversive unconditioned stimulus (US), which is the behavioral basis of exposure therapy for posttraumatic stress disorder (PTSD). However, knowledge about the neurobiology of extinction is insufficient. The present study investigated changes in the protein expression of mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) in the dorsal hippocampus (DH)and ventral hippocampus (VH), induced by extinction and return of conditioned fear responses to an auditory signal. Western blot analysis indicated that shock stress enhanced the expression of MRs in only the DH, whereas extinction selectively increased the expression of MRs in the VH. The infusion of MRs antagonist spironolactone in the VH indicated that MRs in the VH did not affect the retrieval of fear and extinction memories, but facilitated the formation of extinction memory. However, no changes in GRs in either the DH or VH were observed in each phase of auditory fear conditioning. These results suggest that MRs in the DH and VH have differential functions in the extinction of auditory fear conditioning. MRs in the DH appear to be related to only stressful experiences, whereas MRs in the VH are involved in extinction formation. The enhancement of MRs in the VH might be necessary to improve PTSD. PMID- 26271939 TI - The processing course of conflicts in third-party punishment: An event-related potential study. AB - In social decision-making games, uninvolved third parties usually severely punish norm violators, even though the punishment is costly for them. For this irrational behavior, the conflict caused by punishment satisfaction and monetary loss is obvious. In the present study, 18 participants observed a Dictator Game and were asked about their willingness to incur some cost to change the offers by reducing the dictator's money. A response-locked event-related potential (ERP) component, the error negativity or error-related negativity (Ne/ERN), which is evoked by error or conflict, was analyzed to investigate whether a trade-off between irrational punishment and rational private benefit occurred in the brain responses of third parties. We examined the effect of the choice type ("to change the offer" or "not to change the offer") and levels of unfairness (90:10 and 70:30) on Ne/ERN amplitudes. The results indicated that there was an ERN effect for unfair offers as Ne/ERN amplitudes were more negative for not to change the offer choices than for to change the offer choices, which suggested that participants encountered more conflict when they did not change unfair offers. Furthermore, it was implied that altruistic punishment, rather than rational utilitarianism, might be the prepotent tendency for humans that is involved in the early stage of decision-making. PMID- 26271940 TI - Influences of face, stigma, and psychological symptoms on help-seeking attitudes in Macao. AB - The purpose of this study was to examine the relationships between concerns about loss of face, stigma, psychological symptoms, and attitudes toward seeking mental health services such as counseling in Macao. Participants included 391 students attending the largest public university in Macao: 277 were from Macao and 114 were from Mainland China. Participants completed questionnaires measuring attitudes toward seeking professional psychological help, concerns about loss of face, self-stigma, public-stigma, and psychological symptoms. Results showed that positive attitudes toward help-seeking were significantly negatively correlated with self-stigma, public-stigma, and concerns about loss of face but there was no significant correlation with psychological symptoms. Psychological symptoms were positively correlated with face concerns, self-stigma, and public-stigma. Stigma (self and public) was found to be significantly positively associated with face concerns, but the correlations were weak. Findings also showed that Macao students had higher levels of distress, and endorsed greater self- and public stigma than Mainland Chinese students; however, the groups did not differ in face concerns or attitudes toward help-seeking. Regression analysis indicated that group membership was not a significant predictor of help-seeking. Self-stigma was the strongest predictor of professional help-seeking. Age and sex were also found to be significant predictors. Results suggested that younger students were more likely to seek help and that female students reported greater levels of distress and tended to have more positive attitudes toward seeking psychological services than male students. PMID- 26271941 TI - Use of alveolar distraction osteogenesis for implant placement: a case report with eight-year follow-up. AB - Insufficient alveolar ridge width may impede the success of dental implants. Techniques for resolving this problem include autologous bone grafts, guided bone regeneration, bone splitting and bone spreading techniques. Recently, alveolar distraction osteogenesis has become an alternative method for alveolar augmentation. We propose the use of alveolar bone distraction for insufficient alveolar ridge width. A healthy 33-year-old female presented with missing teeth to our clinic. Clinical and radiographic examination revealed the alveolar ridge was too narrow for placement of dental implants. Therefore, horizontal distraction osteogenesis of the posterior mandibular ridge was chosen for augmentation. Two months later, two implants were placed. No significant marginal bone resorption was seen around the implants eight years after placement. Our results indicate that horizontal alveolar distraction is recommended to increase ridge width and allow placement of standard dental implants. PMID- 26271942 TI - Mobilization of horizontally acquired island 2 is induced in planta in the phytopathogen Pectobacterium atrosepticum SCRI1043 and involves the putative relaxase ECA0613 and quorum sensing. AB - Integrative and conjugative elements (ICEs) contribute to the rapid evolution of bacterial pathogens via horizontal gene transfer of virulence determinants. ICEs have common mechanisms for transmission, yet the cues triggering this process under natural environmental or physiological conditions are largely unknown. In this study, mobilization of the putative ICE horizontally acquired island 2 (HAI2), present in the chromosome of the phytopathogen Pectobacterium atrosepticum SCRI1043, was examined during infection of the host plant potato. Under these conditions, mobilization of HAI2 increased markedly compared with in vitro cultures. In planta-induced mobilization of HAI2 was regulated by quorum sensing and involved the putative ICE-encoded relaxase ECA0613. Disruption of ECA0613 also reduced transcription of genes involved in production of coronafacic acid (Cfa), the major virulence factor harboured on HAI2, whereas their expression was unaffected in the quorum-sensing (expI) mutant. Thus, suppression of cfa gene expression was not regulated by the mobilization of the ICE per se, but was due directly to inactivation of the relaxase. The identification of genetic factors associated solely with in planta mobilization of an ICE demonstrates that this process is highly adapted to the natural environment of the bacterial host and can influence the expression of virulence determinants. PMID- 26271943 TI - Pediatric obesity and walking duration increase medial tibiofemoral compartment contact forces. AB - With the high prevalence of pediatric obesity there is a need for structured physical activity during childhood. However, altered tibiofemoral loading during physical activity in obese children likely contribute to their increased risk of orthopedic disorders of the knee. The goal of this study was to determine the effects of pediatric obesity and walking duration on medial and lateral tibiofemoral contact forces. We collected experimental biomechanics data during treadmill walking at 1 m*s(-1) for 20 min in 10 obese and 10 healthy-weight 8-12 year-olds. We created subject-specific musculoskeletal models using radiographic measures of tibiofemoral alignment and centers-of-pressure, and predicted medial and lateral tibiofemoral contact forces at the beginning and end of each trial. Obesity and walking duration affected tibiofemoral loading. At the beginning of the trail, the average percent of the total load passing through the medial compartment during stance was 85% in the obese children and 63% in the healthy weight children; at the end of the trial, the medial distribution was 90% in the obese children and 72% in the healthy-weight children. Medial compartment loading rates were 1.78 times greater in the obese participants. The medial compartment loading rate increased 17% in both groups at the end compared to the beginning of the trial (p = 0.001). We found a strong linear relationship between body-fat percentage and the medial-lateral load distribution (r(2) = 0.79). Altered tibiofemoral loading during walking in obese children may contribute to their increased risk of knee pain and pathology. PMID- 26271944 TI - Influence of nevirapine administration on the pharmacokinetics of dolutegravir in patients infected with HIV-1. AB - OBJECTIVES: The metabolic pathways of dolutegravir and nevirapine suggest a potential pharmacokinetic interaction between these drugs. The objective of this study was to investigate the influence of nevirapine administration on the pharmacokinetics of dolutegravir in patients infected with HIV-1. PATIENTS AND METHODS: This study was an investigator-initiated trial registered at ClinicalTrials.gov under identifier NCT02067767. Dolutegravir (50 mg once daily) was added to the antiretroviral regimen (400 mg of nevirapine once daily + 600/300 mg of abacavir/lamivudine once daily) in 10 adult patients for 5 days. After discontinuation of nevirapine, the combination of dolutegravir + abacavir/lamivudine was continued. Full pharmacokinetic profiles were assessed on the day of nevirapine discontinuation and 2 weeks after discontinuation of nevirapine. The pharmacokinetic parameters of dolutegravir were calculated by non compartmental analysis. The log-transformed values of these parameters were compared between periods with and without nevirapine co-administration. RESULTS: The co-administration of nevirapine led to a significant decrease (P < 0.05) in the area under the plasma concentration-time curve for dolutegravir from the time the dose was administered until the end of the dosing interval (-19%, P = 0.011), as well as decreases in trough plasma concentration (-34%, P = 0.018) and terminal half-life (-15%, P = 0.039), and a significant increase (P < 0.05) in apparent oral clearance for dolutegravir (+23%, P = 0.011). CONCLUSIONS: The decrease in dolutegravir exposure in combination with nevirapine suggests that the metabolism of dolutegravir is induced by nevirapine. According to therapeutic drug monitoring for dolutegravir, some patients may need a higher dose than 50 mg of dolutegravir once daily to maintain the therapeutic plasma concentration throughout the dosing interval. PMID- 26271945 TI - Evolution of Volatile Sulfur Compounds during Wine Fermentation. AB - Volatile sulfur compounds (VSCs) play a significant role in the aroma of foods and beverages. With very low sensory thresholds and strong unpleasant aromas, most VSCs are considered to have a negative impact on wine quality. In this study, headspace solid phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME/GC-MS) was used to analyze the time course of the biosynthesis of 12 VSCs formed during wine fermentation. Two different strains of Saccharomyces cerevisiae, the laboratory strain BY4743 and a commercial strain, F15, were assessed using two media: synthetic grape media and Sauvignon Blanc juice. Seven VSCs were detected above background, with three rising above their sensory thresholds. The data revealed remarkable differences in the timing and evolution of production during fermentation, with a transient spike in methanethiol production early during anaerobic growth. Heavier VSCs such as benzothiazole and S-ethyl thioacetate were produced at a steady rate throughout grape juice fermentation, whereas others, such as diethyl sulfide, appear toward the very end of the winemaking process. The results also demonstrate significant differences between yeast strains and fermentation media. PMID- 26271947 TI - Engineering tailored nanoparticles with microbes: quo vadis? AB - In the quest for less toxic and cleaner methods of nanomaterials production, recent developments in the biosynthesis of nanoparticles have underscored the important role of microorganisms. Their intrinsic ability to withstand variable extremes of temperature, pressure, and pH coupled with the minimal downstream processing requirements provide an attractive route for diverse applications. Yet, controlling the dispersity and facile tuning of the morphology of the nanoparticles of desired chemical compositions remains an ongoing challenge. In this Focus Review, we critically review the advances in nanoparticle synthesis using microbes, ranging from bacteria and fungi to viruses, and discuss new insights into the cellular mechanisms of such formation that may, in the near future, allow complete control over particle morphology and functionalization. In addition to serving as paradigms for cost-effective, biocompatible, and eco friendly synthesis, microbes hold the promise for a unique template for synthesis of tailored nanoparticles targeted at therapeutic and diagnostic platform technologies. PMID- 26271946 TI - Diabetes increases the risk of deep-vein thrombosis and pulmonary embolism. A population-based cohort study. AB - We evaluated the effects of diabetes on the risks of developing deep-vein thrombosis (DVT) and pulmonary embolism (PE) in a nationwide, population-based cohort study in Taiwan. The patients with newly diagnosed type 2 diabetes mellitus (T2DM) were identified, and DM-free controls were randomly selected from the general population and frequency-matched according to age, sex, and index year by using the records of the Longitudinal Health Insurance Database between 2000 and 2011. Both cohorts were followed up until the end of 2011 to measure the incidence of DVT and PE. We analysed the risks of DVT and PE using Cox proportional-hazards regression models. The overall incidence of VTE was higher in the T2DM patients than in the controls (12.0 vs 7.51 per 10,000 person-years). The T2DM patients exhibited a 1.44-fold adjusted hazard ratio (aHR) of VTE development compared with the controls (95% confidence interval [CI] = 1.27 1.63). The risks of DVT (aHR = 1.43, 95% CI = 1.23-1.65) and PE (aHR = 1.52, 95% CI = 1.22-1.90) were greater in the T2DM than those in the controls. The T2DM patients had a substantially higher risk of DVT (aHR = 5.10, 95% CI = 3.12-8.32) and PE (aHR = 7.50, 95% CI = 3.29-17.1) development than the controls did in adults aged 49 years and younger. In conclusion, the longitudinal nationwide cohort study indicated that T2DM patients carried greater risks of developing VTE than did the general population. PMID- 26271948 TI - Localized primary gastrointestinal diffuse large B cell lymphoma received a surgical approach: an analysis of prognostic factors and comparison of staging systems in 101 patients from a single institution. AB - BACKGROUND: Diffuse large B cell lymphoma (DLBCL) represents the most common histological subtype of primary gastrointestinal lymphoma and is a heterogeneous group of disease. Prognostic characterization of individual patients is an essential prerequisite for a proper risk-based therapeutic choice. METHODS: Clinical and pathological prognostic factors were identified, and predictive value of four previously described prognostic systems were assessed in 101 primary gastrointestinal DLBCL (PG-DLBCL) patients with localized disease, including Ann Arbor staging with Musshoff modification, International Prognostic Index (IPI), Lugano classification, and Paris staging system. RESULTS: Univariate factors correlated with inferior survival time were clinical parameters [age>60 years old, multiple extranodal/gastrointestinal involvement, elevated serum lactate dehydrogenase and beta2-microglobulin, and decreased serum albumin], as well as pathological parameters (invasion depth beyond serosa, involvement of regional lymph node or adjacent tissue, Ki-67 index, and Bcl-2 expression). Major independent variables of adverse outcome indicated by multivariate analysis were multiple gastrointestinal involvement. In patients unfit for Rituximab but received surgery, radical surgery significantly prolonged the survival time, comparing with alleviative surgery. Addition of Rituximab could overcome the negative prognostic effect of alleviative surgery. Among the four prognostic systems, IPI and Lugano classification clearly separated patients into different risk groups. IPI was able to further stratify the early-stage patients of Lugano classification into groups with distinct prognosis. CONCLUSIONS: Radical surgery might be proposed for the patients unfit for Rituximab treatment, and a combination of clinical and pathological staging systems was more helpful to predict the disease outcome of PG-DLBCL patients. PMID- 26271950 TI - Oral health in patients treated by positive airway pressure for obstructive sleep apnea: a population-based case-control study. AB - PURPOSE: Recent epidemiological evidence suggests that patients with obstructive sleep apnea (OSA) have an increased risk of periodontal disease. Little is known about the oral health of OSA patients treated by continuous or bi-level positive airway pressure (CPAP/BiPAP). The aim of this population-based case-control study was to compare oral health variables (amount of plaque, calculus, gingival inflammation, and masticatory function) between CPAP/BiPAP users and control subjects. METHODS: The study population was retrieved from a French cohort examined between 2012 and 2013 at the Centre d'Investigations Preventives et Cliniques of Paris. Cases were selected if they reported to be treated by CPAP/BiPAP; controls were age-, gender-, and BMI-matched based on a 1:2 ratio. Univariate and logistic regression analyses were performed for group comparisons. RESULTS: Over a total of 20,436 subjects, 287 CPAP/BiPAP users (mean age (SD) 57.6 years (11.5); 76.3 % males) who underwent medical and dental examinations were compared with 574 matched controls (no OSA, no CPAP/BiPAP). CPAP/BiPAP users reported significantly higher prevalence of diabetes (15.6 vs. 10.3 %; p = 0.012; odds ratio (OR) 1.68), history of hypertension (36.5 vs. 26.1 %; p = 0.003; OR 1.62), cardiovascular diseases (14.1 vs. 8.8 %; p = 0.029; OR 1.69), and sleep complaints (59 vs. 34.4 %; p = 0.0001; OR 2.75). CPAP/BiPAP users also showed higher levels of depression and stress compared to controls. However, no group difference was observed for the amount of dental plaque, calculus, gingival inflammation, and masticatory function. CONCLUSION: Oral health of OSA patients treated by CPAP/BiPAP is comparable to that of matched controls in terms of amount of plaque, gingival inflammation, and masticatory function. PMID- 26271951 TI - Analyses of melatonin, cytokines, and sleep in chronic renal failure. AB - PURPOSE: Inflammation and oxidative stress are involved in the process of chronic renal failure (CRF). CRF patients show indication of sleep disturbances, and the melatonin rhythm, which modulates sleep, is abnormal in these patients; however, it is still unclear whether inflammation could be related to the blockage of melatonin production and sleep disturbances in this population. The aim of this study was to characterize and correlate sleep, the melatonin rhythm, and the levels of the inflammatory cytokines tumor necrosis factor (TNF) and interleukin (IL)-6 in patients with CRF and controls. METHODS: Sleep was evaluated by the "Sleep Quality Index Pittsburgh" (PSQI) questionnaire, and melatonin and cytokine contents in saliva and blood samples, respectively, were analyzed by ELISA. RESULTS: The CRF group scored higher on the global PSQI, which indicates a lower sleep quality and a higher prevalence of sleep disorders, than the control group. The CRF individuals also showed lower melatonin content than the control groups, both during the day and at night, and lacked rhythmicity in melatonin production. The CRF group also showed higher contents of TNF and IL-6 than the control group and a negative correlation between TNF and melatonin content. CONCLUSION: These results suggest that the sleep disorders observed in the CRF group were probably related to the low production of melatonin observed in this population. The high level of TNF, as previously demonstrated in other pathologies, is probably involved in this blockage of melatonin production in CRF. PMID- 26271952 TI - The Endocannabinoid System and its Modulation by Phytocannabinoids. AB - The endocannabinoid system is currently defined as the ensemble of the two 7 transmembrane-domain and G protein-coupled receptors for Delta(9) tetrahydrocannabinol (but not for most other plant cannabinoids or phytocannabinoids)-cannabinoid receptor type-1 (CB1R) and cannabinoid receptor type-2 (CB2R); their two most studied endogenous ligands, the "endocannabinoids" N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG); and the enzymes responsible for endocannabinoid metabolism. However, anandamide and 2 AG, and also the phytocannabinoids, have more molecular targets than just CB1R and CB2R. Furthermore, the endocannabinoids, like most other lipid mediators, have more than just one set of biosynthetic and degrading pathways and enzymes, which they often share with "endocannabinoid-like" mediators that may or may not interact with the same proteins as Delta(9)-tetrahydrocannabinol and other phytocannabinoids. In some cases, these degrading pathways and enzymes lead to molecules that are not inactive and instead interact with other receptors. Finally, some of the metabolic enzymes may also participate in the chemical modification of molecules that have very little to do with endocannabinoid and cannabinoid targets. Here, we review the whole world of ligands, receptors, and enzymes, a true "endocannabinoidome", discovered after the cloning of CB1R and CB2R and the identification of anandamide and 2-AG, and its interactions with phytocannabinoids. PMID- 26271953 TI - Cannabis in the Treatment of Dystonia, Dyskinesias, and Tics. AB - Cannabis has been used for many medicinal purposes, including management of spasms, dystonia, and dyskinesias, with variable success. Its use for tetanus was described in the second century BCE, but the literature continues to include more case reports and surveys of its beneficial effects in managing symptoms of hyperkinetic movement disorders than randomized controlled trials, making evidence-based recommendations difficult. This paper reviews clinical research using various formulations of cannabis (botanical products, oral preparations containing ?(9)-tetrahydrocannabinol and/or cannabidiol) and currently available preparations in the USA (nabilone and dronabinol). This has been expanded from a recent systematic review of cannabis use in several neurologic conditions to include case reports and case series and results of anonymous surveys of patients using cannabis outside of medical settings, with the original evidence classifications marked for those papers that followed research protocols. Despite overlap in some patients, dyskinesias will be treated separately from dystonia and chorea; benefit was not established beyond individual patients for these conditions. Tics, usually due to Tourettes, did respond to cannabis preparations. Side effects reported in the trials will be reviewed but those due to recreational use, including the dystonia that can be secondary to synthetic marijuana preparations, are outside the scope of this paper. PMID- 26271949 TI - Arterial Catheterization and Infection: Toll-like Receptors in Defense against Microorganisms and Therapeutic Implications. AB - Radial artery catheterization has become a preferred route over femoral artery catheterization, in order to monitor the blood pressure of hemodynamically unstable patients or for repeated sampling of arterial blood gases. While the incidence of catheter-related infection is lower in the radial artery than the femoral artery, infection remains a major issue that requires attention. In this review of the literature, we discuss infectious complications of radial artery catheterization, with a focus on various risk factors and establishing the most common causative agents. We also critically review the role of the innate immune system involving Toll-like receptors (TLRs) in host-defense, with the goal of establishing a common pathway used by the innate immune system via TLRs to combat the pathogens that most commonly cause infection in radial artery catheterization. If this pathway can be therapeutically manipulated to preemptively attack pathogenic agents, immunomodulation may be an option in reducing the incidence of infection in this procedure. PMID- 26271956 TI - Applied ethics for nuclear cardiology: Beginning a dialogue. PMID- 26271954 TI - A Distinct Region in Erythropoietin that Induces Immuno/Inflammatory Modulation and Tissue Protection. AB - Beneficial effects of short-term whole-molecule erythropoietin (EPO) therapy have been demonstrated on several animal models of diverse central nervous system pathology. However, the increased hematocrit induced by EPO-driven marrow stimulation greatly limits its potential for side effect-free therapy. We created a library of EPO-derived fragments based on the hypothesis that 2 distinct functions, erythropoiesis and tissue protection, reside in different regions of the molecule. Several small EPO-derived peptides within the Abeta loop of whole EPO molecule were screened for tissue protection in EAE mice. The 19-mer JM-4 peptide that contains 2 cysteine molecules consistently demonstrated the most potent clinical beneficial effects without producing hematocrit alterations in animal models of EAE. The JM-4-induced tissue protection was associated with modulation of the immunoregulatory process that drives inflammation and provokes subsequent autoimmune damage. Like the whole EPO molecule, JM-4 effectively modulated immune/inflammatory reaction within both the peripheral lymphatic tissue and central nervous system. The major effects induced by JM-4 include blocked expansion of monocyte/dendritic antigen presenting cell and T helper 17 cell populations, decreased proinflammatory cytokine production, and sharply enhanced expansion of the regulatory T-cell population. JM-4 shows promise for treatment of a broad spectrum of neural and non-neural conditions associated with inflammation. PMID- 26271957 TI - Collegial pressure and patient-centered shared-decision making: A case-based ethics discussion. PMID- 26271958 TI - How to approach an inappropriately ordered myocardial perfusion stress study: A case-based ethics discussion. PMID- 26271960 TI - Understanding the past to appropriately guide us in the future. PMID- 26271959 TI - Responsibility for follow-up of abnormal findings in myocardial perfusion imaging: A case-based ethics discussion. PMID- 26271955 TI - Suppression Subtractive Hybridization Versus Next-Generation Sequencing in Plant Genetic Engineering: Challenges and Perspectives. AB - Suppression subtractive hybridization (SSH) is an effective method to identify different genes with different expression levels involved in a variety of biological processes. This method has often been used to study molecular mechanisms of plants in complex relationships with different pathogens and a variety of biotic stresses. Compared to other techniques used in gene expression profiling, SSH needs relatively smaller amounts of the initial materials, with lower costs, and fewer false positives present within the results. Extraction of total RNA from plant species rich in phenolic compounds, carbohydrates, and polysaccharides that easily bind to nucleic acids through cellular mechanisms is difficult and needs to be considered. Remarkable advancement has been achieved in the next-generation sequencing (NGS) field. As a result of progress within fields related to molecular chemistry and biology as well as specialized engineering, parallelization in the sequencing reaction has exceptionally enhanced the overall read number of generated sequences per run. Currently available sequencing platforms support an earlier unparalleled view directly into complex mixes associated with RNA in addition to DNA samples. NGS technology has demonstrated the ability to sequence DNA with remarkable swiftness, therefore allowing previously unthinkable scientific accomplishments along with novel biological purposes. However, the massive amounts of data generated by NGS impose a substantial challenge with regard to data safe-keeping and analysis. This review examines some simple but vital points involved in preparing the initial material for SSH and introduces this method as well as its associated applications to detect different novel genes from different plant species. This review evaluates general concepts, basic applications, plus the probable results of NGS technology in genomics, with unique mention of feasible potential tools as well as bioinformatics. PMID- 26271961 TI - Dermatological postoperative patient information leaflets: is it time for more uniformity? AB - INTRODUCTION: Patient information leaflets (PILs) are an important source of information for patients postoperatively. There are currently no nationally agreed standards by dermatologists for postoperative advice following skin surgery. AIM: To assess the common themes and areas of variation in advice given in PILs after skin surgery across all National Health Service (NHS) hospitals in England and Wales. METHODS: All acute trusts in England (n = 159) and local health boards in Wales (n = 7) were requested to provide their postoperative dermatological PILs for general sutured wound care or excision biopsy. Eight preselected parameters were assessed: minimum dressing duration, duration of pressing on a bleeding wound, postoperative analgesia, explanation of infection signs, application of petroleum jelly, scarring, whom to contact if there is a problem, and the recommended postoperative time for abstaining from active exercise. RESULTS: PILs were received from 137 different dermatology departments belonging to 127/166 (76.5%) organisations across England and Wales. Of these, 102 PILs gave a specific duration for dressings: 45/102 (44.1%) advised a minimum of 48 h, but 28/102 (27.5%) recommended leaving dressings in place until suture removal. Regarding duration of pressing on a bleeding wound, 117 PILs gave advice, with the most common recommendation being 15 min (30/117, 25.6%), followed closely by 10 min (26/117, 22.2%). Of the 137 PILs received, 125 gave advice regarding postoperative analgesia, with paracetamol alone being the most common recommendation (24/125, 19.2%). For the remaining parameters, 111/137 (81.0%) PILs described >= 2 signs of infection, 42/137 (30.7%) recommended the application of petroleum jelly, 65/137 (47.4%) mentioned scarring, 137/137 (100%) highlighted whom to contact if there were postoperative problems and 87/137 (63.5%) PILs gave advice regarding postoperative abstinence from active exercise. CONCLUSIONS: The advice given in dermatology postoperative PILs across England and Wales is highly variable. A nationally agreed template or set of postoperative advice should be considered to improve consistency. PMID- 26271962 TI - The Forecast Is Bright: Recent Advances in Melanoma Treatment. PMID- 26271963 TI - The Relationship of Obesity With the Severity of Psoriasis: A Systematic Review. AB - BACKGROUND: Psoriasis is a chronic inflammatory disease associated with obesity. The increased production of adipocytokines in central adiposity contributes to the systemic inflammation of obesity and perhaps to psoriasis. OBJECTIVE: The objective of this systematic review is to determine the association of obesity with psoriasis severity. METHODS: We searched PubMed, EMBASE, and Cochrane Database for English-language papers involving human subjects for all years. We extracted data on age, sex, body mass index (BMI), proportion obese, and psoriasis severity index score (PASI). RESULTS: We identified 254 articles in our search and included 9. The sample size was 134 823 psoriasis patients. Seven of the 9 studies found a statistically significant association of increased psoriasis severity with higher BMI. CONCLUSION: Increased severity of psoriasis appears to be associated with increased BMI. Most studies were cross-sectional or case-control, making it difficult to determine temporality. Dermatologists should consider recording BMI for psoriasis patients and offering them lifestyle counseling. PMID- 26271964 TI - Intralesional Bleomycin for Warts: Patient Satisfaction and Treatment Outcomes. AB - BACKGROUND: The treatment of warts is challenging with regards to both tolerability and efficacy. OBJECTIVE: Ascertain the efficacy, tolerability, and patient satisfaction of intralesional bleomycin in the treatment of warts. METHODS: Retrospective chart review followed by telephone interviews with patients from university-based dermatology referral centers. RESULTS: Seventy four percent (34/46) of patients had complete resolution (CR) of all warts. Of 34 patients who experienced CR, an average of 1.7 treatments were required. Pain experienced during the procedure and recovery, irrespective of outcome, was rated 5.8 out of 10 (range, 1-10; SD, 2.72; SEM, 0.40). Approximately 70% of patients had pain that lasted less than 2 days after treatment. Seventy-eight percent (36/46) of patients in the study were satisfied with treatment and would recommend it to others. CONCLUSION: Patients felt bleomycin to be an effective treatment modality for warts, offering high rates of CR in lesions resistant to more traditional therapies. PMID- 26271965 TI - Microskin Grafting for Stable Vitiligo of the Penis and Vulva: Near Total Uniform Pigmentation. AB - BACKGROUND: The vitiligo of the penis and vulva is a difficult to treat region of the body where the existing surgical repigmentation methods usually do not give satisfactory results. OBJECTIVE: This study was conducted to evaluate the efficacy of microskin grafting in stable genital vitiligo. METHODS: Four male patients and 1 female patient were included in this study, and microskin grafting was performed in the stable vitiliginous areas of genitals under regional anaesthesia. RESULTS: The microskin grafting technique has shown desired results at these sites with near total pigmentation and negligible donor area deformity. CONCLUSION: The microskin grafting for vitiligo is simple, reliable, and the most cost-effective technique of tissue grafting that has all the benefits of the latest cellular grafting techniques without its high cost and infrastructure. PMID- 26271966 TI - Barriers to Treatment of Tinea Capitis in Children Living in the Jane Finch Community of Toronto. AB - BACKGROUND: Tinea capitis is a common fungal infection of the scalp. If left untreated, tinea capitis infection can cause severe inflammatory reactions and the development of kerion. Tinea capitis is effectively treated with oral antifungals, but at present these are not covered under government assistance programs. OBJECTIVE: To assess the potential impact of a limited use code for antifungal therapy in the treatment of childhood tinea capitis. METHOD: Fourteen family physicians practicing in the Jane Finch area were surveyed on their experience treating tinea capitis in this community. RESULTS: Seventy-one percent of surveyed family physicians felt that cost impedes the treatment of tinea capitis in their practice, and 100% felt that a limited use code would have a positive impact on their patients. CONCLUSION: A limited use code for oral antifungal treatments of tinea capitis may provide a simple, cost-effective solution to a major problem impacting children in the Jane Finch area. PMID- 26271969 TI - [Collection and verification of murine allo-transplantation major histocompatibility complex peptides]. AB - OBJECTIVE: To establish a method of collecting transplantation major histocompatibility complex (MHC) peptides. METHODS: Splenic cells of C57BL/6 donor mice were injected into BALB/c recipient mice. The splenic cells of the recipient mice were soaked in pH3.3 citric acid buffer to wash off the MHC conjugated peptides. Peptide contents and components in the elutriant were detected by BCA protein assay and high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Antigenicity of the peptides was verified by murine heterotopic heart transplantation. RESULTS: Fifty micro-gram mixed peptides (including short peptides) per 10(8) cells were collected by the elution method. HPLC-MS/MS revealed that there were differences in peptide components between allo-transplantation group and control group. Medial survival time of heart grafts of same strain MHC peptide pre-immunization group was 8 days, and that of allo-MHC peptide pre-immunization group was 4 days. Medial survival time of heart grafts was shortened significantly by pre-immunization with allo-MHC peptides. CONCLUSION: Transplantation MHC peptides can be obtained by donor splenic cell immunization and elution from recipients' splenic cells with mild acid. They can be used for screening transplantation antigenic determinants. PMID- 26271968 TI - A tangible head model showing semicircular canals for demonstrating the physical treatment for BPPV. AB - CONCLUSIONS: It was shown that practicing with a tangible head model with semicircular canals is a useful educational tool for learning the physical treatment for BPPV. OBJECTIVES: To assess the efficacy of using a tangible head model with semicircular canals to teach the physical treatment for BPPV. METHODS: This study compared the number of canalith particles in the posterior semicircular canal that 20 participants could move from the ampulla to the utricle, before and after practicing with the tangible model. RESULTS: Before practicing with the model, they could move 2.5 (mean value) of 10 canalith particles. However, after practicing, they could move 6.6 (mean value) of 10 canalith particles. There was a statistical difference (p < 0.01) between the two trials. PMID- 26271967 TI - Improved human gingival fibroblast response to titanium implants coated with ultraviolet-irradiated vitamin D precursor and vitamin E. AB - BACKGROUND AND OBJECTIVE: Ultraviolet (UV)-irradiated 7-dehydrocholesterol (7 DHC) and vitamin E (VitE)-coated titanium (Ti) implants have a beneficial effect on bone cells. Human gingival fibroblasts (HGFs) are the most abundant cells in periodontal tissues and are involved in the wound healing and repair. The objective of this study was to evaluate the response of HGFs to Ti implants coated with UV-irradiated 7-DHC and VitE, for improved soft-tissue integration of dental implants. MATERIAL AND METHODS: Ti surfaces were coated with 7-DHC and VitE, irradiated with UV light and incubated for 48 h at 23 degrees C to allow cholecalciferol (D3 ) synthesis from 7-DHC onto the Ti surface. HGFs were cultured on the modified surfaces and the influence of the coating on these cells was evaluated through the analysis of: (i) biocompatibility; (ii) the mRNA levels of genes involved in the composition and turnover of the extracellular matrix, the inflammatory response, periodontal bone resorption and wound healing; and (iii) the levels of MMP-1 and TIMP-1 proteins. RESULTS: We found a beneficial effect of UV-irradiated 7-DHC:VitE-coated Ti implants on HGFs. Besides being biocompatible with HGFs, the UV-irradiated 7-DHC and VitE coating increased the levels of collagen III alpha1 and fibronectin mRNAs. and decreased the level of interleukin-8 mRNA. TIMP-1 was increased at both mRNA and protein levels in HGFs cultured on UV-irradiated 7-DHC:VitE-coated Ti implants. Finally, the UV irradiated 7-DHC and VitE coating decreased the level of RANKL mRNA in HGFs. CONCLUSION: UV-irradiated 7-DHC:VitE-coated Ti implants have a positive effect on HGFs in vitro by reducing the inflammatory response and extracellular matrix breakdown. PMID- 26271970 TI - [Mutation of palmitoylation site of linker for activation of T cells inhibits signal transduction mediated by glycosyl phosphatidyl inositol-anchored CD59 in T cells]. AB - OBJECTIVE: To construct the lentivirus carrying the mutated palmitoylation site of the linker for activation of T cells (LAT) and infect Jurkat cells with it to establish stable cell line, and to investigate the effect of LAT palmitoylation mutation on T cell signaling induced by CD59. METHODS: Negative control (neg EGFP) and LAT-M-EGFP fusion protein gene vectors were respectively constructed and then packaged using lentivirus. Subsequently, Jurkat cells were infected with them to establish stable cell lines. Confocal laser scanning microscopy was used to observe the infection efficiency and the distribution of fusion proteins in Jurkat cells. CCK-8 assay was used to detect the change of cell proliferation activity after CD59 mAb supplementation. Flow cytometry was used to determine the apoptosis rate. Western blotting was used to examine the levels of phospholipase C-gamma1 (PLC-gamma1) and lymphocyte-specific protein tyrosine kinase (LCK). RESULTS: Confocal laser scanning microscopy revealed that LAT molecules of LAT-M group scattered on cell membrane, and there was no obvious clustered region after cross linkage with CD59 mAb. Compared with the negative control group, the cell proliferation activity of LAT-M group significantly decreased, and the quantity of middle-late apoptotic cells significantly increased; Western blotting showed that the expression levels of PLC-gamma1 and LCK in LAT-M group was roughly the same with those in negative control group, and after CD59 mAb stimulation, there was no obvious change in LAT-M group, while the levels in negative control group were reduced. CONCLUSION: LAT-M-EGFP fusion protein could not locate on lipid rafts of Jurkat cells infected with LAT palmitoylation mutation. In addition, the growth of the cells carrying the LAT-M-EGFP was inhibited. The palmitoylation mutation of LAT attenuated the signal transduction induced by glycosylphosphatidylinositol-anchored CD59 in T cells. PMID- 26271971 TI - [Over-expression of augmenter of liver regeneration promotes proliferation and suppresses hydrogen peroxide-induced apoptosis in LO2 cells]. AB - OBJECTIVE: To investigate the effects of over-expression of 23 kDa augmenter of liver regeneration (ALR) on cell proliferation and apoptosis in the normal human hepatic cell line LO2. METHODS: The recombinant plasmid expressing 23 kDa ALR (pcDNA6/23 kDa ALR) was constructed and transfected into LO2 cells with MegaTran 1.0 transfection reagent. The expressions of ALR mRNA and protein in LO2 cells were detected by real-time quantitative PCR and Western blotting, respectively; MTS assay was used to detect the cell proliferation of LO2 cells; cell cycle and apoptosis of LO2 cells were measured by flow cytometry. RESULTS: The recombinant expression plasmid pcDNA6/23 kDa ALR was constructed successfully, and the expression of the target protein 23 kDa ALR increased significantly in the transfected cells. Compared with pcDNA6-myc/HisA group, the transient transfection of pcDNA6/23 kDa ALR into LO2 cells promoted cell proliferation and inhibited cell apoptosis induced by H2O2, however, no significant differences were detected in G0 phase and S phase. CONCLUSION: The over-expression of 23 kDa ALR in LO2 cells promoted the cell proliferation and enhanced cell resistance to H2O2. PMID- 26271972 TI - [Up-regulated expression of FcgammaRIIB inhibits phagocytosis and chemotaxis of macrophages]. AB - OBJECTIVE: To construct an inducible lentivirus vector of FcgammaRIIB and observe its effect on rat macrophages. METHODS: FcgammaRIIB gene fragment was obtained from rat liver mRNA as the template by reverse transcription PCR, and then cloned into tetracycline response element (TRE) plasmid to establish recombinant plasmid TRE-FcgammaRIIB. Lentiviral packaging plasmid was transfected into HEK293T cells together with the recombinant plasmid TRE-FcgammaRIIB and Tet plasmid, respectively. Then the titers of the above lentiviruses were measured. Rat macrophages were co-infected by FcgammaRIIB-lentivirus and Tet-lentivirus, thereafter induced by doxycycline (DOX) of gradient concentrations. The mRNA and protein levels of FcgammaRIIB were measured by immunofluorescence, real-time quantitative PCR (qRT-PCR) and Western blotting. After induced by DOX, macrophages were detected in phagocytic and chemotactic function. RESULTS: The recombinant plasmid we constructed was confirmed correct by PCR, enzyme digestion and sequencing. The titers of FcgammaRIIB-lentivirus and Tet-lentivirus reached 10(6) TU/mL. FcgammaRIIB was expressed under DOX induction in macrophages which were co-infected by the packaged lentiviruses. In addition, FcgammaRIIB level was positively correlated with the concentration of DOX, but was negatively correlated with phagocytosis and chemotaxis of macrophages. CONCLUSION: The up regulation of FcgammaRIIB expression in macrophages might suppress cell phagocytosis and chemotaxis. PMID- 26271973 TI - [Inhibition of proliferation and migration of human umbilical vein endothelial cells by knockdown of cylindromatosis (CYLD) gene]. AB - OBJECTIVE: To down-regulate the expression of cylindromatosis (CYLD) gene by shRNA and investigate its effect on proliferation, migration and cell signal pathways of human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were infected by adenoviruses of CYLD shRNA (experiment group) and GFP (control group), respectively. The proliferation of HUVECs was detected by CCK-8 assay; the cell migration was assessed by a wound healing assay; the related cell signal pathways were analyzed by Western blotting. RESULTS: CCK-8 showed that the proliferation of the CYLD shRNA-infected HUVECs were significantly lower than that of the control group at 1, 2, 3, 4, 5 days after infection. The wound healing assay revealed that the migration rate of the CYLD shRNA-infected HUVECs was significantly reduced compared with the control HUVECs at 48 hours. Western blotting indicated that the phosphorylation of protein kinase B (AKT) and glycogen synthase kinase 3alpha/beta (GSK3alpha/beta) significantly decreased in the CYLD shRNA-infected HUVECs compared with the control HUVECs. CONCLUSION: Inhibiting the expression of CYLD gene can suppress the proliferation and migration of HUVECs, which may be attributed to the inhibition of the AKT/GSK3alpha/beta pathway. PMID- 26271974 TI - [Sirtuin 3 inhibits cardiomyocyte apoptosis by reducing cytochrome C release in myocardiac H9c2 cells with calcium overload]. AB - OBJECTIVE: To investigate the effects of Sirtuin 3 on cytochrome C (CytC) release and caspase-3 activation in myocardiac H9c2 cells with calcium overload. METHODS: H9c2 cells were randomly divided into four groups: control group, Sirtuin 3 group, ionomycin group, ionomycin & Sirtuin 3 group. Myocyte calcium overload models were established by ionomycin revulsion. The levels of CytC and caspase-3 in mitochondria and cytoplasm were examined by Western blotting. Intracellular caspase-3 activity was examined by spectrophotometry. H9c2 cell apoptosis rate in each group was detected by annexin V-FITC/PI double staining combined with flow cytometry. RESULTS: Calcium overload models of H9c2 cells were successfully established. Western blotting showed that CytC level in mitochondria of the ionomycin group was significantly lower than that in the control group, and that it was significantly higher in the ionomycin & Sirtuin 3 group than that in the ionomycin group. Changes of CytC level in cytoplasm was just opposite to that in mitochondria. Caspase-3 level in the ionomycin group was significantly higher than that in the control group, and it was significantly lower in the ionomycin & Sirtuin 3 group than that in the ionomycin group. Spectrophotometry showed that caspase-3 activity in the ionomycin group was significantly higher than that in the control group, and that it was obviously lower in the ionomycin & Sirtuin 3 group than that in the ionomycin group. Flow cytometry combined with double staining revealed that the apoptosis rate in the ionomycin group was significantly higher than that in the control group, and that it was significantly lower in the ionomycin & Sirtuin 3 group than that in the ionomycin group. CONCLUSION: Sirtuin 3 could inhibit cell apoptosis by reducing CytC release and inhibiting caspase-3 activation in cardiomyocyte models with calcium overload. PMID- 26271975 TI - [Inhibition of nuclear factor kappa B mediated by miRNA plasmid carried by novel polyethyleneimine nanogel particles in Kupffer cells of rats]. AB - OBJECTIVE: To test a novel gene carrier, named polyethyleneimine nanogel particles (PEI-NP), for delivering the mircroRNA (miRNA) into Kupffer cells (KCs) for silencing the expression of nuclear transcription factor kappaB (NF-kappaB) P65. METHODS: The capacity of PEI-NPs to carry miRNA was tested by gel electrophoresis. RAW264.7 cell line was transfected with the cationic polymers which mixed together PEI-NP and miRNA. Then, the cytotoxicity of the RAW264.7 cells was detected by cell counting kit-8 (CCK-8); the cell apoptosis and transfection efficiency were analyzed by flow cytometry combined with annexin V FITC/PI staining; the gene and protein levels of NF-kappaB P65 were determined respectively by real-time quantitative PCR (qRT-PCR) and Western blotting. The distribution of the cationic polymers in RAW264.7 cells and liver KCs was observed by transmission electron microscope (TEM). The protein level of NF kappaB P65 in KCs was detected by immunohistochemistry. RESULTS: PEI-NPs were able to completely combine with miRNA at the least mass ratio of 20:1. The highest transfection efficiency of 48 hours was (33.63+/-1.94)% in vitro. The protein level of NF-kappaB P65 at 48 hours of PEI-NP/miRNA transfection into RAW264.7 cells was significantly inhibited. TEM showed the cationic polymers in RAW264.7 cytoplasm and only in KCs of liver tissue after transfection. Immunohistochemistry indicated that the protein expression of NF-kappaB P65 in KCs was significantly lower than that in control group. CONCLUSION: Macrophages and KCs were successfully transfected with the cationic polymers in vitro and in vivo, respectively. The expression of NF-kappaB P65 was knocked down significantly after transfection. PMID- 26271976 TI - [Prediction of regulating network of innate immune signaling molecule hsa-miR 181a in stroke development based on bioinformatics analysis]. AB - OBJECTIVE: To predict the regulating network of innate immunity signaling molecule hsa-miR-181a in stroke based on the methods of bioinformatics. METHODS: The UCSC genome browser, the human miRNA disease database (HMDD), the transcription factor-miRNA regulation database (TransmiR), the database on predicted and validated miRNA targets (miRwalk), the Genecards, the long non coding RNA (LncRNA) disease database, the DIANA LAB-LncBase and the ConSite were employed to study the upstream transcription factor, downstream target genes and the interactive LncRNA of hsa-miR-181a and to draw the core regulating network of hsa-miR-181a. To verify the hsa-miR-181a regulating network, we used lipopolysaccharide (LPS) to stimulate the BV2 cells transfected by lentivirus and real-time quantitative PCR to detect the changes of Toll-like receptor 4 (TLR4), tumor protein 63 (p63), miR-181a and nuclear factor kappaB (NF-kappaB) p65. RESULTS: The UCSC genome browser showed that hsa-miR-181a had two subtypes, which were demonstrated with high conservatism in several species. Diseases analysis and literatures investigation revealed that the hsa-miR-181a was related with many diseases, especially ischemia diseases. Bioinformatics analysis indicated that hsa-miR-181a was regulated by the transcription factors p63, and at the same time, it could regulate 58 target genes such as brain-derived neurotrophic factor (BDNF), TLR4 etc. IncRNA CDKN2B-AS1 and its transcription factors Snail and n-MYC might also interact with hsa-miR-181a. All the relative genes composed a regulatory network with hsa-miR-181a as a core and played important roles in the process of stroke. In LPS-stimulated BV2 cells, the expression levels of TLR4, p63, miR-181a were up-regulated; while the levels of p63, miR-181a and NF-kappaB p65 decreased in the lentivirus-infected BV2 cells, indicating that p63 was the key signaling molecule in the process of TLR4 regulating miR-181a. CONCLUSION: The bioinformatics analysis and preliminary experimental verification predicted and demonstrated the regulating network of hsa-miR-181a in stroke. PMID- 26271977 TI - [Down-regulation of human intercellular adhesion molecule-1 expression in MCF-7 cells infected by lentiviral short hairpin RNA interference vectors]. AB - OBJECTIVE: To construct lentiviral interference vectors of human intercellular adhesion molecule-1 (ICAM-1), then infect human breast cancer MCF-7 cells and identify the interference effects. METHODS: Three short hairpin RNA (shRNA) interference sequences targeting human ICAM-1 gene (ICAM-1 shRNA1, ICAM-1 shRNA2 and ICAM-1 shRNA3) and a negative control sequence (NS) were designed, synthesized and cloned into the pLKO.1-SP6-PGK-GFP vector. After DNA sequencing, three plasmid-based lentiviral packaging system (vector plasmid-psPAX2-pMD2.G) was used to transfect HEK293T cells to package lentiviruses. The supernatants containing viruses were harvested to detect the viral titer. Human MCF-7 breast cancer cells were infected with the lentiviruses and the interference efficiency was detected by real-time quantitative PCR (qRT-PCR) and Western blotting. RESULTS: PCR showed that the designed sequences were successfully inserted into the pLKO.1-SP6-PGK-GFP vector and DNA sequencing results were correct. The qRT PCR and Western blotting showed that the mRNA and protein expression levels of ICAM-1 in the infected MCF-7 cells decreased significantly in the ICAM-1 shRNA3 group. CONCLUSION: Lentiviral interference vectors of human ICAM-1 were constructed successfully and the expression of ICAM-1 in MCF-7 cells was down regulated by ICAM-1 shRNA. PMID- 26271978 TI - [Up-regulated expressions of HIF-1alpha, VEGF and CD34 promote synovial angiogenesis in rats with adjuvant arthritis]. AB - OBJECTIVE: To observe the alterations of hypoxia inducible factor 1alpha (HIF 1alpha), vascular endothelial growth factor (VEGF) and CD34 in synovial tissues in rats with adjuvant arthritis and explore the mechanism of angiogenesis in rheumatoid arthritis. METHODS: Thirty SD rats were randomly divided into normal control and model groups. Adjuvant arthritis was induced using Freund's complete adjuvant in the rats of the model group. Nineteen days after the modeling, the expressions of HIF-1alpha, VEGF and CD34 were detected using immunohistochemistry. The mRNA and protein levels of HIF-1alpha and VEGF were detected by reverse transcription PCR and Western blotting, respectively. RESULTS: Compared with the normal control group, the model group showed paw swelling, increased arthritic index, and significantly up-regulated expressions of VEGF, HIF-1alpha, CD34 in synovial tissue. VEGF mRNA was positively correlated with paw swelling degree, HIF-1alpha protein was positively correlated with the arthritis index, and VEGF mRNA and HIF-1alpha protein were positively correlated with CD34. CONCLUSION: The synovial angiogenesis is associated with the over expressions of VEGF, HIF-1alpha and CD34 in rats with adjuvant arthritis. PMID- 26271979 TI - [The morphological changes of SW620 cells induced by over-expression of human sorting nexin 3]. AB - OBJECTIVE: To explore the effect of human sorting nexin 3 (hSNX3) on the morphology and migration of colorectal cancer cells through over-expression of hSNX3 in SW620 cells. METHODS: A lentiviral vector pEZ-Lv201 (pEZ-SV40-eGFP-IRES Puro) inserted with hSNX3 gene was transferred into SW620 cells to construct and package recombinant lentiviral expression vector pEZ-hSNX3-Lv201. The cell clones stably over-expressing hSNX3 (SW620hSNX3) were screened to observe cell morphology and migration ability using Transwell(TM) assay and wound scratch assay. E-cadherin was detected by Western blotting. RESULTS: Sequence analysis demonstrated that the lentiviral expression vector pEZ-hSNX3-Lv201 was successfully constructed. The packaging titers of the recombinant lentivirus and control virus were 2.12*10(9) copies/mL and 7.9*10(10) copies/mL, respectively. After SW620 cells were transfected with the lentivirus, we got stable hSNX3 overexpressed SW620hSNX3 cells. Most of SW620hSNX3 cells (88%) became oval instead of the original spindle-like shape. However, cell migration ability and expression of E-cadherin showed no significant differences between SW620hSNX3 cells and SW620 cells. CONCLUSION: Over-expression of hSNX3 alters the morphology of SW620 cells, but hardly affects cell migration. PMID- 26271980 TI - [Protective effect of Astragalus polysaccharide on MRC-5 cells from oxidative damage induced by hydrogen peroxide]. AB - OBJECTIVE: To investigate the effects of Astragalus polysaccharide (APS) on the expressions of apurinic/apyrimidinic endonuclease/redox factor-1 (APE/Ref-1) and thioredoxin (TRX) in MRC-5 human embryo lung fibroblasts induced by hydrogen peroxide (H2O2) and explore the mechanism of APS protecting MRC-5 cells from oxidative damage. METHODS: The MRC-5 cells were randomly divided into groups: the normal control group, groups induced by H2O2 of different concentrations, groups treated with 200, 400, 800 mg/L APS. The inhibitory rate of cell proliferation in H2O2-induced MRC-5 cells was measured by MTT assay to make sure the successful establishment of oxidative damage model. With the optimal concentration of H2O2 and different concentrations of APS on MRC-5 cells, we determined the optimal concentrate of APS to prevent oxidative damage in MRC-5 cells. The level of 8 hydroxy-2'-deoxyguanosine (8-OHdG) was detected by immunofluorescence staining. The apoptotic cells were identified by flow cytometry (FCM). The mRNA and protein levels of APE/Ref-1 and TRX were respectively detected by reverse transcription PCR and Western blotting. RESULTS: H2O2 induced oxidative damage in MRC-5 cells in a concentration-dependent manner. We chose the oxidative damage model induced by 800 MUmol/L H2O2 for 24 hours to further study the protective mechanism of APS. Compared with H2O2 control groups, 200 mg/L APS significantly increased the protein level of APE/Ref-1 and TRX, decreased the content of 8-OHdG and the apoptosis of MRC-5 cells, and improved dramatically the cell viability. CONCLUSION: H2O2 can induce oxidative damage in MRC-5 cells. APS can promote APE/Ref-1 and TRX expressions in the damaged MRC-5 cells to relieve the oxidative damage and inhibit cell apoptosis. PMID- 26271981 TI - [Th9 cells and related cytokines increase in the lung of mice with bronchial asthma]. AB - OBJECTIVE: To investigate the number of T helper 9 (Th9) cells and the level of Th9 cell related cytokines in the lung tissues of mice with bronchial asthma and understand their relationship to the pathogenesis of bronchial asthma. METHODS: Sixteen SPF BALB/c mice were randomized into normal group and asthma group (8 mice in each group). After asthmatic models were established, the airway responsiveness was detected with non-invasive lung function machine, ELISA was used for determining the concentrations of cytokine interleukin-9 (IL-9), IL-10 and IL-13 in bronchoalveolar lavage fluid (BALF), HE staining and PAS staining was employed for observing the lung pathological changes, flow cytometry was used for testing the percentages of lung IL-9+ lymphocytes, IL-10+ lymphocytes and IL 13+ lymphocytes in lung CD3+ lymphocytes. RESULTS: Compared with normal group, asthma group showed higher airway responsiveness, more severe airway inflammation and increased concentrations of cytokine IL-9 and IL-13, decreased concentration of cytokine IL-10 in BALF, higher percentages of lung IL-9+ lymphocytes and IL 13+ lymphocytes in CD3+ lymphocytes, and lower percentage of IL-10+ lymphocytes. CONCLUSION: The expression of IL-9 was higher, but IL-10 was lower in asthma group. Th9 cells might play an important role in the pathogenesis of asthma. PMID- 26271982 TI - [Screening of deformed epidermal autoregulatory factor 1-related functional proteins]. AB - OBJECTIVE: To obtain HEK293T cell line which expresses deformed epidermal autoregulatory factor-1 (DEAF1) highly and stably, and to screen candidate proteins which can interact with DEAF1 by co-immunoprecipitation (Co-IP) and mass spectrometry (MS). METHODS: Plasmids pEGFP-mDEAF1 and pEGFP-N1 were transfected into HEK293T and 2F-2B cell lines with TurboFect transfection reagent, respectively. The localization of DEAF1 was observed in the two kinds of cell lines by a fluorescence microscope. Plasmid p3*FLAG-mDEAF1 was transfected into HEK293T and 2F-2B cell lines, respectively. Non-transfected cells were used as a control group. The expression levels of DEAF1 mRNA and protein were detected by reverse transcription PCR, real-time quantitative PCR (qRT-PCR) and Western blotting, respectively. Plasmid p3*FLAG-mDEAF1 was transfected into HEK293T cells, and then HEK293T cell line expressing stably DEAF1 was selected with G418 and identified by Western blotting, immunofluorescence and flow cytometry. Nuclear proteins of HEK293T-DEAF1 and HEK293T cell lines were extracted and detected using Co-IP and SDS-PAGE with EZview(TM) Red ANTI-FLAG M2 affinity gel. Bands, which were obviously enriched and did not exist in the control lanes, were analyzed with MS. RESULTS: DEAF1 was located in the nucleus under the fluorescence microscope. Reverse transcription PCR and qRT-PCR showed that the mRNA level of DEAF1 in DEAF1-expressed HEK293T cells was higher than that in control cell line. Western blotting revealed the expression of mDEAF1-FLAG fusion protein in the transfected cells. HEK293T-DEAF1 cells which expressed DEAF1 highly and stably were obtained successfully. Some candidate proteins which might interact with DEAF1 were screened by Co-IP and MS, such as cytokines and enzymes required for pre-mRNA processing, postinitiation RNA polymerase, and other transcription factors involved in peptide bond breaking and spatial structure formatting, and so on. CONCLUSION: The study obtained HEK293T-DEAF1 cells which expressed DEAF1 highly and stably as well as a large set of candidate proteins which might interact with DEAF1 using Co-IP and MS. PMID- 26271983 TI - [The attachment manner of ubiquitin to proinflammatory molecule discoidin domain receptor 2]. AB - OBJECTIVE: To understand which lysine (K) residue in ubiquitin (Ub) is used to form a poly-Ubs chain on discoidin domain receptor 2 (DDR2). METHODS: The constructs encoding human DDR2 and Cbl-b were transiently transfected into HEK293T cells together with the Ub mutants with lysine mutation at different sites, and the transfected cells were stimulated with collagens in order to induce the activation of DDR2. Immunoprecipitation was performed to isolate DDR2, and the immunoprecipitates were then subjected to immunoblot analysis for the conjugation of DDR2 with Ub. RESULTS: Ub K27-only mutant displayed the strongest poly-Ub chain formation on DDR2, while Ub K33-only mutant exhibited weak ability to be conjugated with DDR2. These findings were further confirmed by Ub K27R and K33R mutants, which reduced DDR2 polyubiquitination. CONCLUSION: DDR2 is linked to a polyUb chain predominantly through K27 conjugation and slightly through K33. PMID- 26271984 TI - [Expressions and co-localization of HIV capsid protein p24 and TRIM22 in HEK293T cells]. AB - OBJECTIVE: To observe the co-localization of human immunodeficiency virus (HIV) capsid protein p24 and tripartite motif containing 22 (TRIM22) in HEK293T cells. METHODS: The retroviral packaging vector pLP1 was used as the template of p24. After the amplification by PCR, the sequence of p24 was cloned into the eukaryotic expression vector pDsRed-Monomer-N1. The recombinant vector was confirmed by colony PCR, double restriction enzyme digestion and DNA sequencing. HEK293T cells were co-transfected with the vector pDsRed-Monomer-N1-p24 together with pEGFP-N3-TRIM22. After 24 hours, the co-localization of p24-DsRed-Monomer and TRIM22-EGFP was detected under a fluorescence microscope. RESULTS: Colony PCR, double restriction enzyme digestion and DNA sequencing confirmed that the eukaryotic expression vector pDsRed-Monomer-N1-p24 was constructed successfully. Fluorescence microscope showed that p24-DsRed-Monomer was co-localized with TRIM22-EGFP in HEK293T cells. CONCLUSION: HIV capsid protein p24 is co-localized with TRIM22 in HEK293T cells. PMID- 26271986 TI - [Leukotriene B4 level in cerebrospinal fluid of patients with tuberculosis meningitis and clinical significance]. AB - OBJECTIVE: To investigate the level of leukotriene B4 (LTB4) in the cerebrospinal fluid (CSF) of patients with tuberculosis meningitis (TBM) and analyze the relationships of LTB4 level with cytological parameters and disease severity. METHODS: By ELISA, LTB4 levels were measured in the CSF of the patients with TBM (diagnosed by modified Ziehl-Neelsen staining), cryptococcal meningitis (CM), central nervous system leukemia (CNSL) or non-inflammatory neurological disease (NIND). CSF cytological testing was performed in TBM patients. Disease severity was evaluated by modified Rankin scale (mRS). LTB4 levels were compared between different disease groups, and the relationships of LTB4 level with white blood cell (WBC) counts, neutrophil counts and disease severity were analyzed statistically. RESULTS: Compared with CM, CNSL or NIND patients, CSF LTB4 level in TBM patients was remarkably higher. CSF LTB4 level in TBM patients was related to neutrophil counts and neutrophil percentages, but not related to WBC counts. No simple linear correlation was found between CSF LTB4 level and disease severity. CONCLUSION: CSF LTB4 level in TBM patients can be used as a predictor of inflammation degree, but its relationship with disease severity and prognosis need further exploration. PMID- 26271985 TI - [The effects of CEACAM6 and FOXP3 on tumor infiltrating lymphocytes and prognosis in patients with pancreatic cancer]. AB - OBJECTIVE: To investigate the expressions of carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) and forkhead box P3 (FOXP3) on tumor infiltrating lymphocytes and prognosis in patients with pancreatic cancer. METHODS: The expressions of CEACAM6, FOXP3, CD3, CD8, CD45RO in pancreatic cancer tissues of 40 cases were assessed by immunohistochemistry, and their relationships with clinicopathological features and prognosis were also analyzed. RESULTS: The strong positive rates of CEACAM6 and FOXP3 in pancreatic cancer tissues were 50% and 60%, respectively. The higher strong positive rate were observed in stage III and IV. High expression of CEACAM6 was negatively correlated with the positive rates of CD8 and CD45RO cells. The strong positive rate of FOXP3 was higher in poorly differentiated pancreatic cancer, and its expression was negatively correlated with the positive rates of CD3, CD8 and CD45RO cells. The patients which had higher expressions of CEACAM6 and FOXP3 had a shorter survival time. CONCLUSION: CEACAM6 and FOXP3 are associated with the malignant degree of pancreatic cancer. The tumor with higher levels of CEACAM6 and FOXP3 shows inhibited T lymphocyte infiltration. PMID- 26271987 TI - [Preparation and application of monoclonal antibody against human myoglobin]. AB - OBJECTIVE: To prepare the monoclonal antibody (mAb) against human myoglobin (MYO) of high titer and specificity and develop double-antibody sandwich ELISA for detecting MYO in human serum samples. METHODS: The BALB/c mice were immunized with natural human MYO, and the hybridoma cell lines secreting anti-MYO mAb were established using cell fusion and hybridoma screening techniques. The characteristics of the mAb were identified after affinity purification from ascites. Then the best antibody pair was selected from mAb to establish a one step sandwich ELISA method. Sixty human serum samples were detected by the homemade ELISA kit and the imported one, respectively. RESULTS: Nine strains of hybridoma cell lines stably secreted anti-MYO mAb. Four strains named 2M1, 3M4, 5M7 and 10M4 could secrete high-quality mAb and the titers of them were in the range of 1.0*10(6) to 2.6*10(6) (A450 value was about 1.0). Three antibody pairs (2M1/HRP-3M4, 5M7/HRP-3M4, 10M4/HRP-5M7) were selected by double-antibody sandwich ELISA. Among them, the 5M7/HRP-3M4 had higher sensitivity and larger linear range. The homemade ELISA kit had a larger linear range (25-1000 ng/mL) than the imported one (25-500 ng/mL) and showed high accuracies in detecting human serum samples, being 95% (19/20) in positive samples and 100% (40/40) in negative samples. CONCLUSION: With the anti-human MYO mAbs of high specificity and affinity, a one-step sandwich ELISA for detecting human MYO has been established successfully, which provides a basis for the development of domestic ELISA kit. PMID- 26271988 TI - [Preparation and application of polyclonal antibody against Ras-related C3 botulinum toxin substrate 1]. AB - OBJECTIVE: To prepare rabbit polyclonal antibody (pAb) against Ras-related C3 botulinum toxin substrate 1 (Rac1) and identify the functions of the antibody. METHODS: The Rac1 fragment was amplified from cDNA of human cervical cancer HeLa cells, and then inserted into the vector pET-32a to construct the recombinant plasmid pET-32a-Rac1. The recombinant protein Rac1 was fused with His-tag and the fusion protein His-Rac1 was expressed in E.coli expression system. Thereafter, His-tagged Rac1 was purified to immunize rabbits as immunogen. The titer and specificity of rabbit polyclonal antibody against Rac1 were identified by ELISA, Western blotting and immunohistochemistry, respectively. RESULTS: The fusion protein His-Rac1 was successfully expressed in E.coli. The pAb could specifically detect Rac1 in human HeLa cells and MCF-7 cells in Western blotting. Moreover, the pAb could specifically recognized Rac1 protein in human kidney tissues. CONCLUSION: The pAb of human Rac1 protein was successfully prepared, which could specifically recognize Rac1 protein in several natural samples. PMID- 26271989 TI - A polymerase engineered for bisulfite sequencing. AB - Bisulfite sequencing is a key methodology in epigenetics. However, the standard workflow of bisulfite sequencing involves heat and strongly basic conditions to convert the intermediary product 5,6-dihydrouridine-6-sulfonate (dhU6S) (generated by reaction of bisulfite with deoxycytidine (dC)) to uracil (dU). These harsh conditions generally lead to sample loss and DNA damage while milder conditions may result in incomplete conversion of intermediates to uracil. Both can lead to poor recovery of bisulfite-treated DNA by the polymerase chain reaction (PCR) as either damaged DNA and/or intermediates of bisulfite treatment are poor substrate for standard DNA polymerases. Here we describe an engineered DNA polymerase (5D4) with an enhanced ability to replicate and PCR amplify bisulfite-treated DNA due to an ability to bypass both DNA lesions and bisulfite intermediates, allowing significantly milder conversion conditions and increased sensitivity in the PCR amplification of bisulfite-treated DNA. Incorporation of the 5D4 DNA polymerase into the bisulfite sequencing workflow thus promises significant sensitivity and efficiency gains. PMID- 26271990 TI - Large-scale profiling of microRNAs for The Cancer Genome Atlas. AB - The comprehensive multiplatform genomics data generated by The Cancer Genome Atlas (TCGA) Research Network is an enabling resource for cancer research. It includes an unprecedented amount of microRNA sequence data: ~11 000 libraries across 33 cancer types. Combined with initiatives like the National Cancer Institute Genomics Cloud Pilots, such data resources will make intensive analysis of large-scale cancer genomics data widely accessible. To support such initiatives, and to enable comparison of TCGA microRNA data to data from other projects, we describe the process that we developed and used to generate the microRNA sequence data, from library construction through to submission of data to repositories. In the context of this process, we describe the computational pipeline that we used to characterize microRNA expression across large patient cohorts. PMID- 26271991 TI - mRNA and DNA selection via protein multimerization: YB-1 as a case study. AB - Translation is tightly regulated in cells for keeping adequate protein levels, this task being notably accomplished by dedicated mRNA-binding proteins recognizing a specific set of mRNAs to repress or facilitate their translation. To select specific mRNAs, mRNA-binding proteins can strongly bind to specific mRNA sequences/structures. However, many mRNA-binding proteins rather display a weak specificity to short and redundant sequences. Here we examined an alternative mechanism by which mRNA-binding proteins could inhibit the translation of specific mRNAs, using YB-1, a major translation regulator, as a case study. Based on a cooperative binding, YB-1 forms stable homo-multimers on some mRNAs while avoiding other mRNAs. Via such inhomogeneous distribution, YB-1 can selectively inhibit translation of mRNAs on which it has formed stable multimers. This novel mechanistic view on mRNA selection may be shared by other proteins considering the elevated occurrence of multimerization among mRNA binding proteins. Interestingly, we also demonstrate how, by using the same mechanism, YB-1 can form multimers on specific DNA structures, which could provide novel insights into YB-1 nuclear functions in DNA repair and multi-drug resistance. PMID- 26271992 TI - Oct-2 forms a complex with Oct-1 on the iNOS promoter and represses transcription by interfering with recruitment of RNA PolII by Oct-1. AB - Oct-1 (POU2f1) and Oct-2 (POU2f2) are members of the POU family of transcription factors. They recognize the same DNA sequence but fulfil distinct functions: Oct 1 is ubiquitous and regulates a variety of genes while Oct-2 is restricted to B cells and neurones. Here we examine the interplay and regulatory mechanisms of these factors to control the inducible nitric oxide synthase (iNOS, NOS2). Using two breast cancer cell lines as a comparative model, we found that MCF-7 express iNOS upon cytokine stimulation while MDA-MB-231 do not. Oct-1 is present in both cell lines but MDA-MB-231 also express high levels of Oct-2. Manipulation of Oct 2 expression in these cell lines demonstrates that it is directly responsible for the repression of iNOS in MDA-MB-231. In MCF-7 cells Oct-1 binds the iNOS promoter, recruits RNA PolII and triggers initiation of transcription. In MDA-MB 231 cells, both Oct-1 and Oct-2 bind the iNOS promoter, forming a higher-order complex which fails to recruit RNA PolII, and as a consequence iNOS transcription does not proceed. Unravelling the mechanisms of transcription factor activity is paramount to the understanding of gene expression patterns that determine cell behaviour. PMID- 26271993 TI - Extensive RPA2 hyperphosphorylation promotes apoptosis in response to DNA replication stress in CHK1 inhibited cells. AB - The replication protein A (RPA)-ssDNA complex formed at arrested replication forks recruits key proteins to activate the ATR-CHK1 signalling cascade. When CHK1 is inhibited during DNA replication stress, RPA2 is extensively hyperphosphorylated. Here, we investigated the role of RPA2 hyperphosphorylation in the fate of cells when CHK1 is inhibited. We show that proteins normally involved in DNA repair (RAD51) or control of RPA phosphorylation (the PP4 protein phosphatase complex) are not recruited to the genome after treatment with CHK1 and DNA synthesis inhibitors. This is not due to RPA2 hyperphosphorylation as suppression of this response does not restore loading suggesting that recruitment requires active CHK1. To determine whether RPA2 hyperphosphorylation protects stalled forks from collapse or induction of apoptosis in CHK1 inhibited cells during replication stress, cells expressing RPA2 genes mutated at key phosphorylation sites were characterized. Mutant RPA2 rescued cells from RPA2 depletion and reduced the level of apoptosis induced by treatment with CHK1 and replication inhibitors however the incidence of double strand breaks was not affected. Our data indicate that RPA2 hyperphosphorylation promotes cell death during replication stress when CHK1 function is compromised but does not appear to be essential for replication fork integrity. PMID- 26271994 TI - Topoisomerase 1-dependent deletions initiated by incision at ribonucleotides are biased to the non-transcribed strand of a highly activated reporter. AB - DNA polymerases incorporate ribonucleoside monophosphates (rNMPs) into genomic DNA at a low level and such rNMPs are efficiently removed in an error-free manner by ribonuclease (RNase) H2. In the absence of RNase H2 in budding yeast, persistent rNMPs give rise to short deletions via a mutagenic process initiated by Topoisomerase 1 (Top1). We examined the activity of a 2-bp, rNMP-dependent deletion hotspot [the (TG)2 hotspot] when on the transcribed or non-transcribed strand (TS or NTS, respectively) of a reporter placed in both orientations near a strong origin of replication. Under low-transcription conditions, hotspot activity depended on whether the (TG)2 sequence was part of the newly synthesized leading or lagging strand of replication. In agreement with an earlier study, deletions occurred at a much higher rate when (TG)2 was on the nascent leading strand. Under high-transcription conditions, however, hotspot activity was not dependent on replication direction, but rather on whether the (TG)2 sequence was on the TS or NTS of the reporter. Deletion rates were several orders of magnitude higher when (TG)2 was on the NTS. These results highlight the complex interplay between replication and transcription in regulating Top1-dependent genetic instability. PMID- 26271995 TI - Challenges for quality management in implementation, maintenance, and sustainability of research tissue biobanks. AB - Availability of high-quality human tissue samples and access to associated histopathological and clinical data is essential for basic and translational biomedical research, especially in areas of personalized medicine, drug, and biomarker development and mechanistically oriented biomedical research projects. Therefore, it is pivotal to establish and maintain quality-assured tissue biobanks that provide high-quality biomaterial to research thereby increasing the impact and reliability of scientific results. Quality concerns do not only address the biomaterial specimen itself but include all biobanking-related procedures. Tissue biobanks thus face essential challenges that encompass the implementation of adequate structural components, documentation of tissue sample collection and storage (procedures), as well as data and project management and IT. An integral and indispensable component of tissue biobanks is expert-driven evaluation (entry and exit controls) of tissue specimen to guarantee provision of high-quality assured biomaterials. PMID- 26271996 TI - The association between bone mineral density, quality of life, quality of sleep and fatigue. AB - OBJECTIVES: This study was undertaken to examine quality of life (QoL), the quality of sleep and fatigue level in postmenopausal women with osteoporosis (OP) but without fractures, to assess the associations between these parameters and to compare the results with those for subjects who have osteopenia or normal bone mineral density (BMD). METHODS: In this study, 113 postmenopausal osteoporosis (PMO) subjects without fractures, 172 subjects with osteopenia and 102 subjects with normal BMD were included. The severity of pain, QoL, quality of sleep and fatigue were assessed using the visual analogue scale (VAS), the QoL Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41), the Pittsburgh Sleep Quality Index (PSQI) and the Checklist of Individual Strength (CIS) questionnaire. RESULTS: No statistically significant differences between the three groups were found in terms of VAS and QUALEFFO-41 total scores (p > 0.05). On the other hand, PSQI and CIS total scores were significantly different in the PMO and osteopenia groups (P = 0.015 and 0.007, respectively) compared to the group with normal BMD. CONCLUSIONS: During the follow-up and treatment of women with PMO or osteopenia, QoL, quality of sleep and fatigue should be assessed and incorporated into treatment decisions, even in the absence of fractures. PMID- 26271998 TI - The viability of mesoporous silica nanoparticles for drug delivery. PMID- 26271997 TI - Do relationships exist between the scope and intensity of quality improvement activities and hospital operation performance? A 10-year observation in Taiwan. AB - BACKGROUND: The relationship between the scope and intensity of quality improvement (QI) activities and hospital performance remains unclear. This study investigated the relationship between performance, external environment, and the scope and intensity of QI activities in hospitals. METHODS: The study used a longitudinal observation. Data regarding the scope and intensity of QI activities were collected using a questionnaire survey among the administrative deputy superintendents / directors of quality management center in 139 hospitals. Hospital performance indicators were abstracted from the 2000-2009 national hospitals profiles. We adopted year 2000 as the baseline, and divided the study period into three 3-year periods. The Generalized Estimating Equations (GEE) model was used for the statistical analysis. RESULTS: Seventy-two hospitals responded to the survey, giving a response rate of 52%. The results showed a significant increase in the scope and intensity of QI activities between 2000 and 2009. The results also showed that the scope and intensity of a hospital's QI activities were associated with the scope and intensity of its competitors' QI activities in the previous period and its own prior performance. The scope of QI activities in the previous period was not significantly related to the selected hospital performance measures. However, the intensity of QI activities in the previous period showed a significant and positive relationship with the number of inpatients and the turnover of beds. CONCLUSION: The study demonstrates that the intensity of QI activities is associated with the external environment and the hospital's own performance in the previous period. Furthermore, some performance measures are associated with the intensity of the QI activities in the previous period. PMID- 26272000 TI - 12th European Federation of Audiology Societies (EFAS) Congress, Istanbul, Turkey, May 27-30th, 2015 Abstract Book. PMID- 26271999 TI - Suspended sediment, carbon and nitrogen transport in a regulated Pyrenean river. AB - Regulation alters the characteristics of rivers by transforming parts of them into lakes, affecting their hydrology and also the physical, chemical, and biological characteristics and dynamics. Reservoirs have proven to be very effective retaining particulate materials, thereby avoiding the downstream transport of suspended sediment and the chemical substances associated with it (e.g. Carbon, C, or Nitrogen, N). The study of fluvial transport of C and N is of great interest since river load represents a major link to the global C and N cycles. Moreover, reservoirs are the most important sinks for organic carbon among inland waters and have a potential significance as nitrogen sinks. In this respect, this paper investigates the effects of a Pyrenean reservoir on the runoff, suspended sediment, C and N derived from the highly active Esera and Isabena rivers. Key findings indicate that the reservoir causes a considerable impact on the Esera-Isabena river fluxes, reducing them dramatically as almost all the inputs are retained within the reservoir. Despite the very dry study year (2011-2012), it can be calculated that almost 300,000 t of suspended sediment were deposited into the Barasona Reservoir, from which more than 16,000 were C (i.e. 2200 t as organic C) and 222 t were N. These values may not be seen as remarkable in a wider global context but, assuming that around 30 h m(3) of sediment are currently stored in the reservoir, figures would increase up to ca. 2.6*10(6) t of C (i.e. 360,000 t of organic C) and 35,000 t of N. Nevertheless, these values are indicative and should be treated with caution as there is incomplete understanding of all the processes which affect C and N. Further investigation to establish a more complete picture of C and N yields and budgets by monitoring the different processes involved is essential. PMID- 26272001 TI - All-solid-state potentiometric sensors with a multiwalled carbon nanotube inner transducing layer for anion detection in environmental samples. AB - While ion to electron transducing layers for the fabrication of potentiometric membrane electrodes for the detection of cations have been well established, similar progress for the sensing of anions has not yet been realized. We report for this reason on a novel approach for the development of all-solid-state anion selective electrodes using lipophilic multiwalled carbon nanotubes (f-MWCNTs) as the inner ion to electron transducing layer. This material can be solvent cast, as it conveniently dissolves in tetrahydrofuran (THF), an important advantage to develop uniform films without the need for using surfactants that might deteriorate the performance of the electrode. Solid contact sensors for carbonate, nitrate, nitrite, and dihydrogen phosphate are fabricated and characterized, and all exhibit comparable analytical characteristics to the inner liquid electrodes. For example, the carbonate sensor exhibits a Nernstian slope of 27.2 +/- 0.8 mV.dec(-1), a LOD = 2.3 MUM, a response time of 1 s, a linear range of four logarithmic units, and a medium-term stability of 0.04 mV.h(-1) is obtained in a pH 8.6 buffered solution. Water layer test, reversibility, and selectivity for chloride, nitrate, and hydroxide are also reported. The excellent properties of f-MWCNTs as a transducer are contrasted to the deficient performance of poly(3-octyl-thiophene) (POT) for carbonate detection. This is evidenced both with a significant drift in the potentiometric measures as well as a pronounced sensitivity to light (either sunlight or artificial light). This latter aspect may compromise its potential for environmental in situ measurements (night/day cycles). The concentration of carbonate is determined in a river sample (Arve river, Geneva) and compared to a reference method (automatic titrator with potentiometric pH detection). The results suggest that nanostructured materials such as f-MWCNTs are an attractive platform as a general ion-to-electron transducer for anion-selective electrodes. PMID- 26272003 TI - Development and Testing of Women's Perception for the Scale of Supportive Care Given During Labor. AB - The aim of this study was to develop and validate women's perceptions of the supportive care received during labor. This study had a methodological design. A total of 360 women giving birth at two state hospitals in 2012 participated. Written permission was obtained from the Ethics Committee, the hospitals, and the participants. Data were collected via participant characteristics forms and the Scale of Women's Perception for Supportive Care Given During Labor. Content validity of the scale (0.94) was achieved with expert views. Three factors comfortable behaviors, education, and disturbing behaviors-were exposed to exploratory factor analysis, and factor loading varied between 0.38 and 0.76. The factor structures were confirmed by confirmatory factor analysis. Cronbach's coefficient was 0.94 for the scale, 0.92 for comforting behaviors, 0.85 for education, and 0.87 for disturbing behaviors. The correlation coefficient between the first and second part of the scale was 0.80. Item-total point correlations of the scale varied between 0.42 and 0.77. The scale was valid and reliable for measuring women's perception of supportive care given during labor. It can be used to determine the care aspects that midwives/nurses should develop, to improve the quality of care, and to help women have more positive labor experiences and higher labor satisfaction. PMID- 26272004 TI - Objective and Subjective Outcomes Following Maxillomandibular Advancement Surgery for Treatment of Patients With Extremely Severe Obstructive Sleep Apnea (Apnea Hypopnea Index >100). AB - PURPOSE: It is important for patients and treating clinicians to know whether maxillomandibular advancement (MMA) surgery is effective when treating patients with obstructive sleep apnea syndrome (OSAS) and an extremely high apnea-hypopnea index (AHI) score. The purpose of this study was to evaluate objective and subjective treatment outcomes after MMA surgery for the treatment of OSAS in patients with a preoperative AHI score higher than 100. PATIENTS AND METHODS: This retrospective study included all patients who underwent MMA surgery for OSAS by members of the Department of Oral and Maxillofacial Surgery, QEII Health Science Centre (Halifax, Nova Scotia, Canada) from November 1996 through February 2014. Objective data were available in the form of polysomnographs (PSGs) obtained before and a minimum of 6 months after surgery. Patients completed a self-administered questionnaire before and after surgery regarding snoring, witnessed apneas, continuous positive airway pressure (CPAP) use, daytime somnolence, and overall satisfaction. RESULTS: Two hundred sixty-five patients had MMA surgery, of which 13 had pre- and postoperative PSGs. PSGs showed a mean preoperative AHI score of 117.9 and a mean postsurgical AHI score of 16.1 (P < .001). Pre- and postoperative questionnaires were available for 9 patients. After surgery, 7 patients denied having any daytime sleepiness and 2 patients reported minimal daytime sleepiness. The mean preoperative Epworth Sleepiness Scale score was 12.9 (standard deviation [SD], 5.5), whereas the postoperative mean score was 5.0 (SD, 4.1; P = .004). Before surgery, all 9 patients reported loud snoring and 8 reported witnessed apneas. After surgery, 2 patients reported minimal snoring and only 1 patient continued to have witnessed apneas. Six patients used CPAP preoperatively and only 1 patient continued to use CPAP after surgery. CONCLUSIONS: The results of this study suggest that MMA surgery for treatment of extremely severe OSA can be a highly successful 1-stage surgery, which eliminates the use of CPAP, improves subjective outcomes, and considerably decreases the AHI score. PMID- 26272005 TI - Single-Fraction Helical Tomotherapy for Ameloblastic Carcinoma. AB - Ameloblastic carcinoma (AC) is a rare malignant odontogenic tumor. Surgical resection of the tumor is the mainstay of its treatment. To date, radiotherapy for this tumor remains controversial. This report describes a case of AC with intracranial extension and provides the first report of the efficacy of single fraction helical tomotherapy for the treatment of residual AC after surgical resection. PMID- 26272006 TI - Current Role of Carnoy's Solution in Treating Keratocystic Odontogenic Tumors. AB - PURPOSE: To understand the frequency of use of Carnoy's solution, as a means of chemical curettage, for treating the keratocystic odontogenic tumor (KCOT). MATERIALS AND METHODS: A Web-based survey was distributed by e-mail to 6,880 members listed in the 2013 American Association of Oral and Maxillofacial Surgeons directory. RESULTS: Eight hundred nine participants across the United States responded to the survey (12% response rate). The most common procedures performed to definitively treat a KCOT were enucleation plus mechanical curettage (curette with or without peripheral ostectomy; 66%). Of the survey participants, 198 (25%) currently use Carnoy's solution, 111 (56%) of whom are using the solution with chloroform and 83 (42%) are using it without chloroform. CONCLUSION: Carnoy's solution remains a common method of chemical curettage for the definitive treatment of the KCOT. Carnoy's solution with and without chloroform is being used for chemical cautery. PMID- 26272007 TI - SmartWatch by SmartMonitor: Assessment of Seizure Detection Efficacy for Various Seizure Types in Children, a Large Prospective Single-Center Study. AB - INTRODUCTION: Patients with epilepsy and their caregivers are constantly burdened with the possibility of a seizure and its consequences, such as accidents, injuries, and sudden unexplained death in epilepsy. It is the unpredictable nature of seizures that often affects both patients with seizures and their caregivers, limits independence, and hinders quality of life. There are several types of motion detectors on the market, each with varying degrees of sensitivity. MATERIAL AND METHODS: We prospectively tested the SmartWatch, a wrist-worn monitor, on children, adolescents, and young adults with various types of seizures in an epilepsy monitoring unit. Confirmation of seizure type and if there was rhythmic upper extremity jerking associated with the seizure was determined by review of the video electroencephalograph. This was compared with the standard detection system of the watch. RESULTS: This study analyzed a total of 191 seizures in 41 patients aged 5-41 years. Fifty-one of the seizures were generalized tonic-clonic. Forty-seven of the seizures had a rhythmic arm movement component. The SmartWatch detected 30 seizures (16%) of the total, 16 (31%) of the generalized tonic-clonic seizures, and 16 (34%) seizures associated with rhythmic arm movements. DISCUSSION: Overall, only a minority of generalized tonic clonic seizures or seizures with rhythmic movements were detected, highlighting the need for an effective seizure detection device. PMID- 26272008 TI - An international comparison of reimbursement for DIEAP flap breast reconstruction. AB - INTRODUCTION: The deep inferior epigastric artery perforator (DIEAP) flap is currently considered the gold standard for autologous breast reconstruction. With the current economic climate and health cutbacks, we decided to survey reimbursement for DIEAP flaps performed at the main international centres in order to assess whether they are funded consistently. METHODS: Data were collected confidentially from the main international centres by an anonymous questionnaire. RESULTS: Our results illustrate the wide disparity in international DIEAP flap breast reconstruction reimbursement: a unilateral DIEAP flap performed in New York, USA, attracts ?20,759, whereas the same operation in Madrid, Spain, will only be reimbursed for ?300. Only 35.7% of the surgeons can set up their own fee. Moreover, 85.7% of the participants estimated that the current fees are insufficient, and most of them feel that we are evolving towards an even lower reimbursement rate. In 55.8% of the countries represented, there is no DIEAP-specific coding; in comparison, 74.4% of the represented countries have a specific coding for transverse rectus abdominis (TRAM) flaps. Finally, despite the fact that DIEAP flaps have become the gold standard for breast reconstruction, they comprise only a small percentage of all the total number of breast reconstruction procedures performed (7-15%), with the only exception being Belgium (40%). CONCLUSION: Our results demonstrate that DIEAP flap breast reconstruction is inconsistently funded. Unfortunately though, it appears that the current reimbursement offered by many countries may dissuade institutions and surgeons from offering this procedure. However, substantial evidence exists supporting the cost-effectiveness of perforator flaps for breast reconstruction, and, in our opinion, the long-term clinical benefits for our patients are so important that this investment of time and money is absolutely essential. PMID- 26272009 TI - Fistula after single-stage primary hypospadias repair - A systematic review of the literature. AB - BACKGROUND: The reporting of fistula after hypospadias repair varies greatly in the worldwide literature, with incidence ranging from 0% to over 35%. With multiple techniques employed within a heterogeneous patient cohort, to date, no "average" incidence of fistula has been reported. METHODS: A systematic review of the contemporary English-language literature from 2005 to 2015 identifying articles reporting complications after primary, single-stage hypospadias repair (the most commonly performed hypospadias operation) was performed. Identified reports were reviewed according to the Consolidated Standards of Reporting Trials (CONSORT) and the Methodological Index or Non-Randomized Studies (MINORS). A random effects analysis model was produced, in order to calculate a pooled outcome rates across the included studies. Separate models were then produced for subgroups of studies, with the resulting pooled rates compared. RESULTS: After application of inclusion and exclusion criteria, 44 articles progressed to the final analysis. A total of 6603 patients were included. The incidence of fistula was 7.5% (95% CI: 5.8-9.4), stricture or stenosis 4.4% (95% CI: 3.1-5.8) and dehiscence 2.1% (95% CI: 1.3-3.1). CONCLUSIONS: With pooled proportions of complications from over 6600 patients over a 10-year period, a standard may be set for outcomes after single-stage primary hypospadias repair for surgeons to audit their own outcomes against. PMID- 26272012 TI - Simple Suturing Technique for Umbilical Dimple Wound after Single-Incision Laparoscopic Surgery. PMID- 26272010 TI - Transit-time ultrasound technology-assisted lymphatic supermicrosurgery. PMID- 26272013 TI - Parenchyma-Sparing Liver Surgery for Large Segment 1 Tumors: Ultrasound-Guided Lateral and Superior Approaches as Safe Alternatives to Major Hepatectomy. PMID- 26272011 TI - Effect of negative pressure on growth, secretion and biofilm formation of Staphylococcus aureus. AB - Negative pressure wound therapy (NPWT) has gained popularity in the management of contaminated wounds as an effective physical therapy, although its influence on the bacteria in the wounds remains unclear. In this study, we attempted to explore the effect of negative pressure conditions on Staphylococcus aureus, the most frequently isolated pathogen during wound infection. S. aureus was cultured in Luria-Bertani medium at subatmospheric pressure of -125 mmHg for 24 h, with the bacteria grown at ambient pressure as the control. The application of negative pressure was found to slow down the growth rate and inhibit biofilm development of S. aureus, which was confirmed by static biofilm assays. Furthermore, decreases in the total amount of virulence factors and biofilm components were observed, including alpha-hemolysin, extracellular adherence protein, polysaccharide intercellular adhesin and extracellular DNA. With quantitative RT-PCR analysis, we also revealed a significant inhibition in the transcription of virulence and regulatory genes related to wound infections and bacterial biofilms. Together, these findings indicated that negative pressure could inhibit the growth, virulence and biofilm formation of S. aureus. A topical subatmospheric pressure condition, such as NPWT, may be a potential antivirulence and antibiofilm strategy in the field of wound care. PMID- 26272014 TI - Can 360-Degree Reviews Help Surgeons? Evaluation of Multisource Feedback for Surgeons in a Multi-Institutional Quality Improvement Project. AB - BACKGROUND: Medical organizations have increased interest in identifying and improving behaviors that threaten team performance and patient safety. Three hundred and sixty degree evaluations of surgeons were performed at 8 academically affiliated hospitals with a common Code of Excellence. We evaluate participant perceptions and make recommendations for future use. STUDY DESIGN: Three hundred and eighty-five surgeons in a variety of specialties underwent 360-degree evaluations, with a median of 29 reviewers each (interquartile range 23 to 36). Beginning 6 months after evaluation, surgeons, department heads, and reviewers completed follow-up surveys evaluating accuracy of feedback, willingness to participate in repeat evaluations, and behavior change. RESULTS: Survey response rate was 31% for surgeons (118 of 385), 59% for department heads (10 of 17), and 36% for reviewers (1,042 of 2,928). Eighty-seven percent of surgeons (95% CI, 75% 94%) agreed that reviewers provided accurate feedback. Similarly, 80% of department heads believed the feedback accurately reflected performance of surgeons within their department. Sixty percent of surgeon respondents (95% CI, 49%-75%) reported making changes to their practice based on feedback received. Seventy percent of reviewers (95% CI, 69%-74%) believed the evaluation process was valuable, with 82% (95% CI, 79%-84%) willing to participate in future 360 degree reviews. Thirty-two percent of reviewers (95% CI, 29%-35%) reported perceiving behavior change in surgeons. CONCLUSIONS: Three hundred and sixty degree evaluations can provide a practical, systematic, and subjectively accurate assessment of surgeon performance without undue reviewer burden. The process was found to result in beneficial behavior change, according to surgeons and their coworkers. PMID- 26272015 TI - Investigating the Impact of the 2011 ACGME Resident Duty Hour Regulations on Surgical Residency Programs: The Program Director Perspective. AB - BACKGROUND: The 2011 ACGME regulations required substantial changes to the structure of general surgery residency programs, due primarily to the 16-hour in house rule for PGY1 residents. However, the scope of changes that programs have undertaken to meet these requirements, and the educational impact of those changes, are poorly understood. STUDY DESIGN: We performed in-depth qualitative interviews with general surgery program directors. Twenty program directors participated in the study; interviews were conducted until adequate thematic saturation was achieved. Participants were recruited from a stratified random sampling of residency programs in the United States to ensure a representative cohort. Interviews focused on changes in call schedule, interns' educational requirements, development, and satisfaction. RESULTS: Most programs used a month long night float (NF) rotation (14 of 20 [75%]). A minority of programs (5 of 20 [25%]) used a weekly rotating schedule, in which interns worked 5 to 6 nights in a month. Multiple programs (65%) had an NF in place before 2011; these programs made changes to and expanded their existing schedule to accommodate the new regulations. Commonly cited challenges to instituting NF included weekend coverage (60%) and providing adequate days off during day-to-night transition. Interns spent as much as 3 months of the year on NF. Only 5 programs made explicit changes to teaching schedules or developed a curriculum for residents on NF. Seventy-five percent of programs excused interns, explicitly or implicitly, from didactic teaching when on NF. Common themes noted by program directors included delayed maturation of trainees, interns being isolated from the team culture, and a conflict between the professional behaviors of "following the rules" and "doing what is right." PMID- 26272016 TI - Preoperative Glycosylated Hemoglobin and Postoperative Glucose Together Predict Major Complications after Abdominal Surgery. AB - BACKGROUND: Glycosylated hemoglobin (HbA1c) is diagnostic of and a measure of the quality of control of diabetes mellitus. Both HbA1c and perioperative hyperglycemia have been targeted as modifiable risk factors for postoperative complications. The HbA1c percent cutoff that best predicts major complications has not been defined. STUDY DESIGN: A prospective study of all abdominal operations from a single institution from 2007 to 2010 was performed. All patients with HbA1c within 3 months before surgery were included. The primary end point was major complication, using the Clavien-Dindo complication system, within 30 days of surgery. Stepwise, multivariate analysis was performed including clinically relevant variables chosen a priori. RESULTS: Among 438 patients who had a measured HbA1c, 96 (21.9%) experienced a major complication. On multivariate analysis, HbA1c >= 6.5% (odds ratio = 1.95; 95% CI, 1.17-3.24; p = 0.01) was found to be the most significant predictor of major complications. Glyosylated hemoglobin and glucose were strongly correlated (correlation coefficient 0.414, p < 0.01). Predicted probabilities demonstrated that both HbA1c and glucose together contributed to major complications; and HbA1c impacted the ability to achieve optimal perioperative glucose control. Patients with a BMI >30 kg/m(2), history of coronary artery disease, and nonwhite race were more likely to have a HbA1c >= 6.5%. CONCLUSIONS: Elevated HbA1c >= 6.5% and perioperative hyperglycemia were associated with an increased rate of major complications after abdominal surgery. Elevated peak postoperative glucose levels were correlated with elevated HbA1c and were independently associated with major complications. More liberal HbA1c testing should be considered in high-risk patients before elective surgery. Safe, feasible, and effective strategies to reduce both HbA1c and perioperative hyperglycemia need to be developed to optimize patient outcomes. PMID- 26272017 TI - Is Laparoscopy Contraindicated for Gallbladder Cancer? A 10-Year Prospective Cohort Study. AB - BACKGROUND: Laparoscopic treatment for gallbladder cancer (GBC) has long been contraindicated, but few studies have demonstrated the oncologic outcomes of this treatment. The purpose of this study was to evaluate long-term survival after intended laparoscopic surgery for early-stage GBC based on our 10 years of experience. STUDY DESIGN: Between May 2004 and April 2014, eighty-three patients suspected of having early-stage GBC with no evidence of liver invasion were enrolled in the prospective protocol for laparoscopic surgery. Data for 45 of these patients with pathologically proven GBC were analyzed to determine the safety and oncologic outcomes of a laparoscopic approach to GBC. Twenty-six patients whose postoperative follow-up exceeded 5 years were investigated to determine the 5-year actual survival outcomes. RESULTS: Extended cholecystectomy, including laparoscopic lymphadenectomy, was performed in 32 patients and simple cholecystectomy in 13 patients. The T stages based on final pathologic results were Tis (n = 2), T1a (n = 10), T1b (n = 8), and T2 (n = 25). After a median follow-up of 60 months after surgery, recurrence was detected in 4 patients as distant metastases. There was no local recurrence around the gallbladder bed or lymphadenectomy. Disease-specific 5-year survival rate of the 45 patients was 94.2%. Disease-specific actual survival rate of 26 patients whose postoperative follow-up period exceeded 5 years was 92.3% at 5 years. CONCLUSIONS: The favorable long-term oncologic results shown in this study confirm the oncologic safety of laparoscopic cholecystectomy, including laparoscopic lymphadenectomy in selected patients with GBC. PMID- 26272019 TI - Valence-based Word-Face Stroop task reveals differential emotional interference in patients with major depression. AB - Word-Face Stroop task creates emotional conflict between affective words and affective faces. In this task, healthy participants consistently slow down while responding to incongruent cases. Such interference related slowdown is associated with recruitment of inhibitory processes to eliminate task-irrelevant information. We created a valence-based Word-Face Stroop task, in which participants were asked to indicate whether the words in the foreground are positive, negative or neutral. Healthy participants were faster and more accurate than un-medicated patients with major depression disorder (MDD). In addition, a significant congruence by group interaction is observed: healthy participants slowed down for incongruent cases, but MDD patients did not. Furthermore, for the negative words, healthy individuals made more errors while responding to incongruent cases but MDD patients made the lowest number of errors for this category. The emotional percepts of the patients were intact, because correct response rates in word valence judgments for positive/negative words, and reaction times for happy/sad faces had similar patterns with those of controls. These findings are supported by the analytical rumination interpretation of depression: patients lose speed/accuracy in laboratory tasks due to processing load spent during continuous rumination. However, for tasks in line with their preoccupation, continual practice makes the patients more vigilant and adept. PMID- 26272020 TI - Adjustment disorder as proposed for ICD-11: Dimensionality and symptom differentiation. AB - Although Adjustment Disorder as a diagnostic category is widely used in clinical practice it is critically discussed that it has not been conceptualized as a category with unique symptoms. Hence, the conceptualization of Adjustment Disorder is subject to substantive change in ICD-11 including core symptoms and additional features in a uni-faceted concept. Adjustment Disorder was assessed with a self-rating instrument in a representative sample of the German general population (N=2512). Confirmatory factor analyses (CFA) were applied to test the dimensionality of symptoms according to the new diagnostic concept. Latent class analysis (LCA) was applied to test whether there are distinguishable subgroups with respect to symptomatology. 2.0% of the sample were diagnosed with Adjustment Disorder according to the new diagnostic algorithm. The proposed six factor model shows best fit with good reliability of the factors in the CFA compared to competing models. However the factors are highly correlated and not distinguishable. The LCA identified three latent classes, reflecting low, mild and moderate to severe symptoms. The findings support the uni-faceted concept of Adjustment Disorder as it is conceptualized in the new diagnostic concept in ICD 11 in a general population sample. This clearer diagnostic concept will inform research as well as clinical practice. PMID- 26272022 TI - Exploring cognitive heterogeneity in first-episode psychosis: What cluster analysis can reveal. AB - Variable outcomes in first-episode psychosis (FEP) are partly attributable to heterogeneity in cognitive functioning. To aid identification of those likely to have poorer or better outcomes, we examined whether purported cognitive profiles identified through use of cluster analysis in chronic schizophrenia were evident in FEP. We also aimed to assess whether there was a relationship between cognitive profile and factors independent of the solution, providing external validation that the cognitive profiles represented distinct subgroups. Ward's method hierarchical cluster analysis, verified by a k-means cluster solution, was performed using data obtained from a cognitive test battery administered to 128 participants aged 15-25 years. Four cognitive profiles were identified. A continuity element was evident; participants in cluster four were more cognitively impaired compared to participants in cluster three, who appeared more cognitively intact. Clusters one and two were distinguishable across measures of attention and working memory and visual recognition memory, most likely reflecting sample specific patterns of deficit. Participants in cluster four had significantly lower premorbid and current IQ and higher negative symptoms compared to participants in cluster three. The distinct levels and patterns of cognition found in chronic schizophrenia cohorts are also evident across diagnostic categories in FEP. PMID- 26272021 TI - The association between childhood trauma and facial emotion recognition in adults with bipolar disorder. AB - Many patients with bipolar disorder (BD) have difficulties in facial emotion recognition, which may also be impaired in maltreated children and in subjects who have a positive history of childhood traumatic experiences. Childhood trauma is reported with a high prevalence in BD and it is considered a risk factor for the disorder. As the relationship between facial emotion recognition and childhood trauma in BD has not yet been directly investigated, in this study we examined whether the presence of a childhood trauma in affectively stable BD patients was associated with poorer performance in emotion recognition. Seventy five BD I and II participants completed the Childhood Trauma Questionnaire retrospectively assessing five types of childhood trauma (emotional, physical and sexual abuse, and emotional and physical neglect) and the Emotion Recognition Task evaluating the ability to correctly identify six basic facial emotions (happiness, sadness, anger, disgust, fear and surprise). Our results suggest that the presence of childhood trauma in participants with BD is associated with a more severe clinical presentation (earlier onset, longer duration of illness, and higher depressive symptom ratings) and that BD patients with a positive childhood history of emotional neglect perform worse than those without such a history in recognizing anger. PMID- 26272023 TI - Emotional memory in pregnant women at risk for postpartum depression. AB - Postpartum depression (PPD) is associated with debilitating effects on mothers and their infants. A previous history of depression is considered the strongest risk factor for PPD. Depressed individuals recall more negative than positive content and higher levels of stress hormones released during encoding are associated with enhanced recall of emotional stimuli. This study examined the impact of a previous history of major depressive disorder (MDD) and pregnancy on emotional memory. Seventy-seven participants completed the study [44 pregnant women in the second trimester of pregnancy with and without a lifetime history of MDD and 33 non-pregnant women with and without a lifetime history of MDD]. All completed an encoding task and provided salivary cortisol (sCORT) and alpha amylase (sAA) samples. Participants returned one week later for a surprise incidental recognition memory task. Women with a history of MDD had worse recognition than women without a history of MDD for negative, but not positive images; this effect was independent of sCORT and sAA levels. Pregnancy did not affect emotional memory. Considering that several previous studies found enhanced memory bias for negative content during depressive states, our results suggest that clinical remission may be associated with an opposite cognitive processing of negative emotional content. PMID- 26272024 TI - The estrogen receptor alpha nuclear localization sequence is critical for fulvestrant-induced degradation of the receptor. AB - Fulvestrant, a selective estrogen receptor down-regulator (SERD) is a pure competitive antagonist of estrogen receptor alpha (ERalpha). Fulvestrant binds ERalpha and reduces the receptor's half-life by increasing protein turnover, however, its mechanism of action is not fully understood. In this study, we show that removal of the ERalpha nuclear localization sequence (ERDeltaNLS) resulted in a predominantly cytoplasmic ERalpha that was degraded in response to 17-beta estradiol (E2) but was resistant to degradation by fulvestrant. ERDeltaNLS bound the ligands and exhibited receptor interaction similar to ERalpha, indicating that the lack of degradation was not due to disruption of these processes. Forcing ERDeltaNLS into the nucleus with a heterologous SV40-NLS did not restore degradation, suggesting that the NLS domain itself, and not merely receptor localization, is critical for fulvestrant-induced ERalpha degradation. Indeed, cloning of the endogenous ERalpha NLS onto the N-terminus of ERDeltaNLS significantly restored both its nuclear localization and turnover in response to fulvestrant. Moreover, mutation of the sumoylation targets K266 and K268 within the NLS impaired fulvestrant-induced ERalpha degradation. In conclusion, our study provides evidence for the unique role of the ERalpha NLS in fulvestrant induced degradation of the receptor. PMID- 26272025 TI - A Lactobacillus plantarum strain isolated from kefir protects against intestinal infection with Yersinia enterocolitica O9 and modulates immunity in mice. AB - Lactobacillus plantarum C4, previously isolated from kefir and characterized as a potential probiotic strain, was tested for its protective and immunomodulatory capacity in a murine model of yersiniosis. The inoculation of BALB/c mice with a low pathogenicity serotype O9 strain of Yersinia enterocolitica results in a prolonged intestinal infection with colonization of Peyer's patches. Pretreatment with C4 was without effect on fecal excretion of yersiniae, but shortened the colonization of Peyer's patches. This protective effect was associated with pro inflammatory status in the intestinal mucosa (TNF-alpha production in infected mice was increased by C4) and an increase in total IgA secretion. At a systemic level, C4 did not promote a pro-inflammatory response, although production of the immunoregulatory cytokine IFN-gamma was enhanced. These findings suggest that L. plantarum C4 can increase resistance to intestinal infections through its immunomodulatory activity. PMID- 26272027 TI - Susceptibility loci for sporadic brain arteriovenous malformation; a replication study and meta-analysis. AB - BACKGROUND: Case-control studies have reported multiple genetic loci to be associated with sporadic brain arteriovenous malformations (AVMs) but most of these have not been replicated in independent populations. The aim of this study was to find additional evidence for these reported associations and perform a meta-analysis including all previously published results. METHODS: We included 167 Dutch patients and 1038 Dutch controls. Case genotyping was performed by KASPar assays. Controls had been previously genotyped with a genome wide single nucleotide polymorphisms (SNP) array. Differences in genotype frequencies between cases and controls were estimated by chi(2) testing in Plink V.1.07. Meta analysis was performed in RevMan V.5.3. RESULTS: In our case-control study we found no significant association with brain AVM (BAVM) for previously discovered SNPs near ANGPTL4, IL-1beta, GPR124, VEGFA and MMP-3. The meta-analysis revealed a statistically significant association with BAVMs for the polymorphism rs11672433 near ANGPTL4 (OR 1.39; 95% CI 1.10 to 1.75, p value 0.005). CONCLUSIONS: The results of this study support a role for the previously identified SNP near ANGPTL4 in the pathogenesis of AVMs. Previously found associations with SNPs near IL-1beta, GPR124, VEGFA and MMP-3 genes could not be substantiated in our replication cohort or in the meta-analysis. PMID- 26272026 TI - Inhibition of the Aurora A kinase augments the anti-tumor efficacy of oncolytic measles virotherapy. AB - Oncolytic measles virus (MV) strains have demonstrated broad spectrum preclinical anti-tumor efficacy, including breast cancer. Aurora A kinase controls mitotic spindle formation and has a critical role in malignant transformation. We hypothesized that the Aurora A kinase inhibitor MLN8237 (alisertib) can increase MV oncolytic effect and efficacy by causing mitotic arrest. Alisertib enhanced MV oncolysis in vitro and significantly improved outcome in vivo against breast cancer xenografts. In a disseminated MDA-231-lu-P4 lung metastatic model, the MV/alisertib combination treatment markedly increased median survival to 82.5 days with 20% of the animals being long-term survivors versus 48 days median survival for the control animals. Similarly, in a pleural effusion model of advanced breast cancer, the MV/alisertib combination significantly improved outcome with a 74.5 day median survival versus the single agent groups (57 and 40 days, respectively). Increased viral gene expression and IL-24 upregulation were demonstrated, representing possible mechanisms for the observed increase in anti tumor effect. Inhibiting Aurora A kinase with alisertib represents a novel approach to enhance MV-mediated oncolysis and antitumor effect. Both oncolytic MV strains and alisertib are currently tested in clinical trials, this study therefore provides the basis for translational applications of this combinatorial strategy in the treatment of patients with advanced breast cancer. PMID- 26272028 TI - A longitudinal study of cortical grey matter lesion subtypes in relapse-onset multiple sclerosis. AB - BACKGROUND: Cortical grey matter (GM) lesions are common in multiple sclerosis (MS), but little is known about their temporal evolution. We investigated this in people with relapsing-remitting (RR) and secondary progressive (SP) MS. METHODS: 27 people with RRMS, and 22 with SPMS were included in this study. Phase sensitive inversion recovery scans were acquired on 2 occasions. Cortical GM lesions were classified as intracortical (IC, only involving GM) and leucocortical (LC, mixed GM-white matter (WM)); WM lesions touching the cortex as juxtacortical (JC). On follow-up scans, new IC, LC and JC lesions were identified, and any change in classification of lesions previously observed was noted. WM lesion counts in the whole brain were assessed on PD/T2-weighted scans. RESULTS: Over a mean (SD) of 21.0 (5.8) months, the number of new IC lesions per person per year was greater in SPMS (1.6 (1.9)) than RRMS (0.8 (1.9)) (Mann Whitney p=0.039). All new LC lesions arose from previously seen IC lesions (SPMS 1.4 (1.8) per person per year, and RRMS 1.1 (1.0)), and none arose de novo, or from previously seen JC lesions. Changes in cortical GM (either new IC or IC converting to LC) lesion counts did not correlate with the changes in WM lesion counts. CONCLUSIONS: New cortical GM lesions rarely arise from the WM and the rate of new IC lesion formation is not closely linked with WM lesion accrual. IC lesion formation appears to be more common in SPMS than RRMS. PMID- 26272029 TI - Comparison of retraction phenomenon and BI-RADS-US descriptors in differentiating benign and malignant breast masses using an automated breast volume scanner. AB - OBJECTIVE: To compare the diagnostic values of retraction phenomenon in the coronal planes and descriptors in the Breast Imaging Reporting and Data System Ultrasound (BI-RADS-US) lexicon in differentiating benign and malignant breast masses using an automated breast volume scanner (ABVS). MATERIALS AND METHODS: Two hundred and eight female patients with 237 pathologically proven breast masses (120 benign and 117 malignant) were included in this study. ABVS was performed for each mass after preoperative localization by conventional ultrasonography (US). Multivariate logistic regression analysis was performed to assess independent variables for malignancy prediction. Diagnostic performance was evaluated through the receiver operating characteristic (ROC) curve analysis. RESULTS: Retraction phenomenon (odds ratio [OR]: 76.70; 95% confidence interval [CI]: 12.55, 468.70; P<0.001) was the strongest independent predictor for malignant masses, followed by microlobulated margins (OR: 55.87; 95% CI: 12.56, 248.44; P<0.001), angular margins (OR: 36.44; 95% CI: 4.55, 292.06; P=0.001), calcifications (OR: 5.53; 95% CI: 1.34, 22.88; P=0.018,) and patient age (OR: 1.10; 95% CI: 1.03, 1.17; P=0.004). Mass shape, orientation, echo pattern, indistinct margins, spiculated margins, and mass size were not significantly associated with breast malignancy. Area under the ROC curve (Az) for microlobulated margins and retraction phenomenon was higher than that for other significant independent predictors. Az, sensitivity, and specificity were 0.877 (95% CI: 0.829, 0.926) and 0.838 (95% CI: 0.783, 0.892), 82.9% and 70.1%, and 92.5% and 98.3%, respectively, for microlobulated margins and retraction phenomenon. CONCLUSIONS: Retraction phenomenon and microlobulated margins have high diagnostic values in the differentiation of benign and malignant breast masses using an ABVS. PMID- 26272030 TI - Mammography with and without radiolucent positioning sheets: Comparison of projected breast area, pain experience, radiation dose and technical image quality. AB - PURPOSE: To compare projected breast area, image quality, pain experience and radiation dose between mammography performed with and without radiolucent positioning sheets. METHODS: 184 women screened in the Dutch breast screening programme (May-June 2012) provided written informed consent to have one additional image taken with positioning sheets. 5 cases were excluded (missing data). Pain was scored using the Numeric Rating Scale. Radiation dose was estimated using the Dance model and projected breast area using computer software. Two radiologists and two radiographers assessed image quality. RESULTS: With positioning sheets significantly more pectoral muscle, lateral and medial breast tissue was projected (CC-views) and more and deeper depicted pectoral muscle (MLO-views). In contrast, visibility of white and darker areas was better on images without positioning sheets, radiologists were therefore better able to detect abnormalities (MLO-views). Women experienced more pain with positioning sheets (MLO-views only, mean difference NRS 0.98; SD 1.71; p=0,00). CONCLUSION: Mammograms with positioning sheets showed more breast tissue. Increased breast thickness after compression with sheets resulted in less visibility of white and darker areas and thus reduced detection of abnormalities. Also, women experienced more pain (MLO-views) due to the sheet material. A practical consideration is the fact that more subcutaneous fat tissue and skin are being pulled forward leading to folds in the nipple area. On balance, improvement to the current design is required before implementation in screening practice can be considered. PMID- 26272031 TI - Multiparametric Magnetic Resonance Imaging Predicts Postoperative Pathology but Misses Aggressive Prostate Cancers as Assessed by Cell Cycle Progression Score. AB - PURPOSE: We identified prognostic biomarkers in prostate cancer by a radiogenomics strategy that integrates gene expression using the cell cycle progression score and medical images. MATERIALS AND METHODS: We obtained institutional review board approval and written informed consent from 106 men with prostate cancer, including 60% at low risk, who underwent multiparametric magnetic resonance imaging before radical prostatectomy was done and a cell cycle progression score was determined. The correlation between the results of multiparametric magnetic resonance imaging and Gleason grade or cell cycle progression score was assessed by logistic regression. RESULTS: Patients with primary Gleason grade greater than 3 had a longer median maximal tumor diameter (13 vs 10 mm) and a lower median apparent diffusion coefficient (0.745 vs 0.88*10(-3) mm2 per second, each p=0.0001) than those with primary Gleason grade 3 or less. Maximal diameter 10 mm or greater (OR 4.9, 95% CI 1.7 to 14.0, p=0.0012) and apparent diffusion coefficient 0.80*10(-3) mm2 per second or less (OR 7.5, 95% CI 3.0 to 18.7, p<0.0001) were significantly associated with primary Gleason grade greater than 3. The combined measure of maximal diameter less than 10 mm and apparent diffusion coefficient greater than 0.80*10(-3) mm2 per second identified only index lesions harboring primary Gleason grade 3. However, 7 of those lesions showed a molecular pattern of high risk lethal prostate cancer (cell cycle progression score greater than 0). CONCLUSIONS: Multiparametric magnetic resonance imaging is able to predict low and high risk Gleason scores in the tumor. However, the cell cycle progression score did not completely match the imaging result. These findings suggest that management of early stages prostate cancer could strongly benefit by performing magnetic resonance imaging targeted biopsy coupled with molecular analysis. PMID- 26272034 TI - Studies of the physicochemical and structural properties of self-assembling cationic pyridine derivatives as gene delivery agents. AB - New amphiphilic pyridine derivatives containing dodecyloxycarbonyl substituents at positions 3 and 5 and cationic moieties at positions 2 and 6 have been designed and synthesised. Compounds of this type can be considered as synthetic lipids. The corresponding 1,4-dihydropyridine (1,4-DHP) derivatives have earlier been proposed as a promising tool for plasmid DNA (pDNA) delivery in vitro. In this work studies of the self-assembling properties of amphiphilic pyridine derivatives leading to the formation of liposomes, determination of particle size, zeta-potential and critical micelle concentration (CMC) with dynamic light scattering (DLS) measurements are described. Furthermore, thermal analysis of pyridine derivatives was performed using thermogravimetry analysis (TGA) and differential thermal analysis (DTA) as well as the ability to deliver the pEGFP C1 plasmid DNA (that encodes GFP reporter) into the Baby hamster kidney-derived (BHK-21) cell line was used for evaluation of gene delivery properties. We have revealed that the new pyridine derivatives possessed self-assembling properties which were proved by formation of nanoparticles with the average size from 115 to 743nm, the zeta-potentials in the range of 48-79mV and CMC values in the range of 2-67MUM. DTA data showed that all processes were endothermic for all compounds. Additionally, we established that among the tested pyridines the representatives with N-methylpyrrolidinium or pyridinium moieties as cationic head-group at the positions 2 and 6 possessed higher pEGFP-C1 transfection activity into the BHK-21 cell line. Nevertheless, the obtained results indicated that correlation of the physicochemical, structural properties and gene delivery activities of the tested compounds were not completely elucidated yet. On the other hand, the synthesised pyridines as possible metabolites of promising delivery systems on the 1,4-DHP core possessed lower pDNA transfection activity than the corresponding 1,4-DHP amphiphiles. PMID- 26272035 TI - Identifying compound efficacy targets in phenotypic drug discovery. AB - The identification of the efficacy target(s) for hits from phenotypic compound screens remains a key step to progress compounds into drug development. In addition to efficacy targets, the characterization of epistatic proteins influencing compound activity often facilitates the elucidation of the underlying mechanism of action; and, further, early determination of off-targets that cause potentially unwanted secondary phenotypes helps in assessing potential liabilities. This short review discusses the most important technologies currently available for characterizing the direct and indirect target space of bioactive compounds following phenotypic screening. We present a comprehensive strategy employing complementary approaches to balance individual technology strengths and weaknesses. PMID- 26272033 TI - Pulmonary endothelial cell barrier enhancement by novel FTY720 analogs: methoxy FTY720, fluoro-FTY720, and beta-glucuronide-FTY720. AB - Effective therapeutic agents are lacking for the prevention and reversal of vascular leak, a frequent pathophysiologic result of inflammatory processes such as acute respiratory distress syndrome (ARDS) and sepsis. We previously demonstrated the potent barrier-enhancing effects of related compounds sphingosine 1-phosphate (S1P), the pharmaceutical agent FTY720, and its analog (S)-FTY720 phosphonate (Tys) in models of inflammatory lung injury. In this study, we characterize additional novel FTY720 analogs for their potential to reduce vascular leak as well as utilize them as tools to better understand the mechanisms by which this class of agents modulates permeability. Transendothelial resistance (TER) and labeled dextran studies demonstrate that (R)-methoxy-FTY720 ((R)-OMe-FTY), (R)/(S)-fluoro-FTY720 (FTY-F), and beta-glucuronide-FTY720 (FTY-G) compounds display in vitro barrier-enhancing properties comparable or superior to FTY720 and S1P. In contrast, the (S)-methoxy-FTY720 ((S)-OMe-FTY) analog disrupts lung endothelial cell (EC) barrier integrity in TER studies in association with actin stress fiber formation and robust intracellular calcium release, but independent of myosin light chain or ERK phosphorylation. Additional mechanistic studies with (R)-OMe-FTY, FTY-F, and FTY-G suggest that lung EC barrier enhancement is mediated through lipid raft signaling, Gi-linked receptor coupling to downstream tyrosine phosphorylation events, and S1PR1-dependent receptor ligation. These results provide important mechanistic insights into modulation of pulmonary vascular barrier function by FTY720-related compounds and highlight common signaling events that may assist the development of novel therapeutic tools in the prevention or reversal of the pulmonary vascular leak that characterizes ARDS. PMID- 26272036 TI - In silico assessment of adverse drug reactions and associated mechanisms. AB - During recent years, various in silico approaches have been developed to estimate chemical and biological drug features, for example chemical fragments, protein targets, pathways, among others, that correlate with adverse drug reactions (ADRs) and explain the associated mechanisms. These features have also been used for the creation of predictive models that enable estimation of ADRs during the early stages of drug development. In this review, we discuss various in silico approaches to predict these features for a certain drug, estimate correlations with ADRs, establish causal relationships between selected features and ADR mechanisms and create corresponding predictive models. PMID- 26272032 TI - Structure-activity studies of Wnt/beta-catenin inhibition in the Niclosamide chemotype: Identification of derivatives with improved drug exposure. AB - The Wnt signaling pathway plays a key role in regulation of organ development and tissue homeostasis. Dysregulated Wnt activity is one of the major underlying mechanisms responsible for many diseases including cancer. We previously reported the FDA-approved anthelmintic drug Niclosamide inhibits Wnt/beta-catenin signaling and suppresses colon cancer cell growth in vitro and in vivo. Niclosamide is a multi-functional drug that possesses important biological activity in addition to inhibition of Wnt/beta-catenin signaling. Here, we studied the SAR of Wnt signaling inhibition in the anilide and salicylamide region of Niclosamide. We found that the 4'-nitro substituent can be effectively replaced by trifluoromethyl or chlorine and that the potency of inhibition was dependent on the substitution pattern in the anilide ring. Non-anilide, N-methyl amides and reverse amide derivatives lost significant potency, while acylated salicylamide derivatives inhibited signaling with potency similar to non-acyl derivatives. Niclosamide's low systemic exposure when dosed orally may hinder its use to treat systemic disease. To overcome this limitation we identified an acyl derivative of Niclosamide, DK-520 (compound 32), that significantly increased both the plasma concentration and the duration of exposure of Niclosamide when dosed orally. The studies herein provide a medicinal chemical foundation to improve the pharmacokinetic exposure of Niclosamide and Wnt-signaling inhibitors based on the Niclosamide chemotype. The identification of novel derivatives of Niclosamide that metabolize to Niclosamide and increase its drug exposure may provide important research tools for in vivo studies and provide drug candidates for treating cancers with dysregulated Wnt signaling including drug-resistant cancers. Moreover, since Niclosamide is a multi-functional drug, new research tools such as DK520 could directly result in novel treatments against bacterial and viral infection, lupus, and metabolic diseases such as type II diabetes, NASH and NAFLD. PMID- 26272037 TI - Psychopathic traits in adolescents are associated with higher structural connectivity. AB - Altered structural connectivity has been reported in antisocial juveniles, but findings have been inconsistent. Given the phenotypical heterogeneity among individuals showing antisocial behavior, specification of the association between structural connectivity and the dimensions of psychopathic traits (i.e., callous unemotional, grandiose-manipulative, and impulsive-irresponsible traits) may aid in more reliably elucidating the neural mechanisms underlying antisocial behavior during adolescence. In this study, a sample of 145 adolescents (mean age 17.6, SD 1.6) from a childhood arrestee cohort participated in a neuroimaging protocol including diffusion tensor imaging (DTI). Fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD), as obtained by tract-based spatial statistics, were associated with juveniles' scores on the Youth Psychopathic Traits Inventory. Grandiose-manipulative traits were positively associated with FA and negatively with RD in a wide range of white matter tracts, suggesting abnormal myelination related to these traits. Callous-unemotional traits were positively associated with FA and AD in specific white matter tracts, including the corpus callosum and corticospinal tract. The differential associations between dimensions of psychopathic traits and measures of structural connectivity support the notion that multiple distinct neural mechanisms underlie antisocial and psychopathic development. PMID- 26272038 TI - Striatal dopamine type 2 receptor availability in anorexia nervosa. AB - The neurobiology of anorexia nervosa remains incompletely understood. Here we utilized PET imaging with the radiotracer [(11)C]raclopride to measure striatal dopamine type 2 (D2) receptor availability in patients with anorexia nervosa. 25 women with anorexia nervosa who were receiving treatment in an inpatient program participated, as well as 25 control subjects. Patients were scanned up to two times with the PET tracer [(11)C]raclopride: once while underweight, and once upon weight restoration. Control subjects underwent one PET scan. In the primary analyses, there were no significant differences between underweight patients (n=21) and control subjects (n=25) in striatal D2 receptor binding potential. Analysis of subregions (sensorimotor striatum, associative striatum, limbic striatum) did not reveal differences between groups. In patients completing both scans (n=15), there were no detectable changes in striatal D2 receptor binding potential after weight restoration. In this sample, there were no differences in striatal D2 receptor binding potential between patients with anorexia nervosa and control subjects. Weight restoration was not associated with a change in striatal D2 receptor binding. These findings suggest that disturbances in reward processing in this disorder are not attributable to abnormal D2 receptor characteristics, and that other reward-related neural targets may be of greater relevance. PMID- 26272040 TI - The pharmacology of bitter taste receptors and their role in human airways. AB - The receptors involved in bitter taste perception (bitter taste receptors--T2Rs) constitute a family of G-protein-coupled receptors, of which around 29 subtypes have been identified in humans. T2R expression was initially thought to be confined to the oral cavity but has recently been described in a range of other tissues (such as the heart, gut, nasal cavity and lungs) and cell types (chemosensory, smooth muscle, endothelial, epithelial and inflammatory cells). Although it is still not clear whether endogenous T2R agonists exist, the T2R receptors recognize many natural and synthetic compounds, such as the acyl homoserine lactones produced by bacteria, caffeine, chloroquine, and erythromycin. In the upper airways, T2Rs are involved in neurogenic inflammation and bacterial clearance. Their known effects in the lungs are exerted at three different levels. Firstly, T2R agonists increase the beating frequency of cilia on epithelial cells. Secondly, the T2Rs induce bronchial smooth muscle cells to relax. Thirdly, the T2R receptors expressed on immune cells (such as macrophages and mast cells) modulate production of pro-inflammatory mediators. Furthermore, T2R agonists are effective in inhibiting lung inflammation or smooth muscle contraction in ex vivo and asthma animal models, and are known to be involved in bacterial killing in the nasal cavity and enhancing lung function in humans. This review focuses on the pharmacology and physiological functions of T2R receptors in the upper and lower airways. It presents recently acquired knowledge suggesting that T2Rs may become valuable drug targets in the treatment of diseases such as asthma and chronic rhinosinusitis. PMID- 26272039 TI - Motor overflow in children with attention-deficit/hyperactivity disorder is associated with decreased extent of neural activation in the motor cortex. AB - Motor overflow is a developmental phenomenon that typically disappears by late childhood. Abnormal persistence of motor overflow is often present in children with attention-deficit/hyperactivity disorder (ADHD). This study employed functional magnetic resonance imaging (fMRI) during a finger-sequencing task to examine whether excessive motor overflow in children with ADHD is associated with decreased extent of motor circuit activation. Thirty-four right-handed children (18 typically developing controls, 16 ADHD) completed fMRI while performing a finger-sequencing task. Motor overflow was evaluated during a finger-sequencing task and a motor examination (the PANESS) performed outside the scanner. Diagnostic differences in behavioral measures of overflow and extent of activation in the contralateral and ipsilateral motor network ROIs were examined, along with correlations between overflow and extent of activation. Children with ADHD demonstrated greater overflow and lesser extent of activation in left primary motor cortex (BA4) and bilateral premotor cortex (BA6) and supplementary motor area (SMA) during right-hand finger-sequencing compared to controls. Decreased extent of primary motor and premotor activation correlated with increased hand-related overflow movements in children with ADHD but not controls. These findings suggest that overflow movements in children with ADHD may reflect decreased recruitment of neural circuitry involved in active inhibition of homologous motor circuitry unnecessary to task execution. PMID- 26272041 TI - Large single crystal growth, transport property, and spectroscopic characterizations of three-dimensional Dirac semimetal Cd3As2. AB - The three dimensional (3D) Dirac semimetal is a new quantum state of matter that has attracted much attention recently in physics and material science. Here, we report on the growth of large plate-like single crystals of Cd3As2 in two major orientations by a self-selecting vapor growth (SSVG) method, and the optimum growth conditions have been experimentally determined. The crystalline imperfections and electrical properties of the crystals were examined with transmission electron microscopy (TEM), scanning tunneling microscopy (STM), and transport property measurements. This SSVG method makes it possible to control the as-grown crystal compositions with excess Cd or As leading to mobilities near 5-10(5) cm(2)V(-1)s(-1). Zn-doping can effectively reduce the carrier density to reach the maximum residual resistivity ratio (RRRrho300K/rho5K) of 7.6. A vacuum cleaved single crystal has been investigated using angle-resolved photoemission spectroscopy (ARPES) to reveal a single Dirac cone near the center of the surface Brillouin zone with a binding energy of approximately 200 meV. PMID- 26272042 TI - The KICA Carer: informant information to enhance the Kimberley Indigenous Cognitive Assessment. AB - BACKGROUND: A quality dementia-screening tool is required for older remote Aboriginal Australians who have high rates of dementia and limited access to appropriate medical equipment and clinicians. The Kimberley Indigenous Cognitive Assessment (KICA Cog) is a valid cognitive test for dementia in Aboriginal and Torres Strait Islander peoples. The KICA cognitive informant questionnaire (KICA Carer) had yet to be analyzed to determine validity alone or in combination with the KICA Cog. METHODS: The KICA Carer was completed by nominated informants of 349 remote-living Aboriginal Australians in the Kimberley region, Western Australia. Validity was assessed by comparing KICA Carer with Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and International Classification of Diseases (ICD-10) consensus diagnoses based on a blinded specialist review. KICA Carer and KICA Cog were then compared to determine joint validity. RESULTS: A KICA Carer score of >=3/16 gave optimum sensitivity (76.2%) and specificity (81.4%), area under curve (AUC) 0.89 (95% CI = 0.85, 0.94) with positive predictive value (PPV) of 35.8%, and negative predictive value (NPV) of 96.2%. A KICA Cog score of <=33/39 gave a sensitivity of 92.9% and specificity of 89.9%, AUC 0.96 (95% CI = 0.94, 0.98), with PPV of 55.6% and NPV of 98.9%. Cut-off scores of KICA Cog <= 33/39 and KICA Carer >= 2/16 in series indicate possible dementia, with sensitivity of 90.5% and specificity of 93.5%. In this setting, PPV was 66.5% and NPV was 98.6%. CONCLUSIONS: The KICA Carer is an important tool to accurately screen dementia in remote Aboriginal Australians when the KICA Cog is unable to be used for a patient. It is readily accepted by caregivers. KEY POINTS: * For the best practice in the cognitive assessment of an Aboriginal Australian aged over 45 years, KICA Cog should be utilized. * In cases where Aboriginal patients are not assessed directly, KICA Carer should be conducted with an informant. A cut-off score of >=3/16 should be used (these tools can be downloaded from www.wacha.org.au/kica.html). PMID- 26272043 TI - Myristoylation confers noncanonical AMPK functions in autophagy selectivity and mitochondrial surveillance. AB - AMP-activated protein kinase (AMPK) plays a central role in cellular energy sensing and bioenergetics. However, the role of AMPK in surveillance of mitochondrial damage and induction of mitophagy remains unclear. We demonstrate herein that AMPK is required for efficient mitophagy. Mitochondrial damage induces a physical association of AMPK with ATG16-ATG5-12 and an AMPK-dependent recruitment of the VPS34 and ATG16 complexes with the mitochondria. Targeting AMPK to the mitochondria is both sufficient to induce mitophagy and to promote cell survival. Recruitment of AMPK to the mitochondria requires N-myristoylation of AMPKbeta by the type-I N-myristoyltransferase 1 (NMT1). Our data support a spatiotemporal model wherein recruitment of AMPK in association with components of the VPS34 and ATG16 complex to damaged mitochondria regulates selective mitophagy to maintain cancer cell viability. PMID- 26272044 TI - The expanding spectrum of EBV+ lymphomas. AB - In this issue of Blood, Nicolae et al at the National Cancer Institute describe a series of Epstein-Barr virus-positive (EBV+) diffuse large B-cell lymphomas (DLBCLs) in young patients (median age 23 years) without known immunodeficiency. PMID- 26272045 TI - C3dg-CR3 interaction in erythrophagocytosis. AB - In this issue of Blood, Lin et al elegantly demonstrate that the erythrocytes from patients with paroxysmal nocturnal hemoglobinuria (PNH) undergoing eculizumab treatment, which are opsonized with the complement C3dg, can interact with complement receptor 3 (CR3) on activated monocytes, thus leading to erythrophagocytosis. PMID- 26272046 TI - Game, set, match for factor VIII mismatch? AB - In this issue of Blood, Gunasekera et al provide evidence that the high rate of factor VIII (FVIII) inhibitors seen in black hemophilia A (HA) patients is not due to a mismatch between the structure of treatment products and FVIII genotypes common in blacks. PMID- 26272047 TI - COMP: an endogenous thrombin inhibitor. AB - In this issue of Blood, Liang and colleagues demonstrate that cartilage oligomeric matrix protein (COMP) acts as a major endogenous plasma- and platelet derived inhibitor of thrombin activity in vitro and in vivo. PMID- 26272048 TI - Guidelines for determination of the number of prior lines of therapy in multiple myeloma. PMID- 26272049 TI - Specific Inhibition of Phosphodiesterase-4B Results in Anxiolysis and Facilitates Memory Acquisition. AB - Cognitive dysfunction is a core feature of dementia and a prominent feature in psychiatric disease. As non-redundant regulators of intracellular cAMP gradients, phosphodiesterases (PDE) mediate fundamental aspects of brain function relevant to learning, memory, and higher cognitive functions. Phosphodiesterase-4B (PDE4B) is an important phosphodiesterase in the hippocampal formation, is a major Disrupted in Schizophrenia 1 (DISC1) binding partner and is itself a risk gene for psychiatric illness. To define the effects of specific inhibition of the PDE4B subtype, we generated mice with a catalytic domain mutant form of PDE4B (Y358C) that has decreased ability to hydrolyze cAMP. Structural modeling predictions of decreased function and impaired binding with DISC1 were confirmed in cell assays. Phenotypic characterization of the PDE4B(Y358C) mice revealed facilitated phosphorylation of CREB, decreased binding to DISC1, and upregulation of DISC1 and beta-Arrestin in hippocampus and amygdala. In behavioral assays, PDE4B(Y358C) mice displayed decreased anxiety and increased exploration, as well as cognitive enhancement across several tests of learning and memory, consistent with synaptic changes including enhanced long-term potentiation and impaired depotentiation ex vivo. PDE4B(Y358C) mice also demonstrated enhanced neurogenesis. Contextual fear memory, though intact at 24 h, was decreased at 7 days in PDE4B(Y358C) mice, an effect replicated pharmacologically with a non selective PDE4 inhibitor, implicating cAMP signaling by PDE4B in a very late phase of consolidation. No effect of the PDE4B(Y358C) mutation was observed in the prepulse inhibition and forced swim tests. Our data establish specific inhibition of PDE4B as a promising therapeutic approach for disorders of cognition and anxiety, and a putative target for pathological fear memory. PMID- 26272050 TI - Oxytocin Facilitates Pavlovian Fear Learning in Males. AB - In human evolution, social group living and Pavlovian fear conditioning have evolved as adaptive mechanisms promoting survival and reproductive success. The evolutionarily conserved hypothalamic peptide oxytocin is a key modulator of human sociality, but its effects on fear conditioning are still elusive. In the present randomized controlled study involving 97 healthy male subjects, we therefore employed functional magnetic resonance imaging and simultaneous skin conductance response (SCR) measures to characterize the modulatory influence of intranasal oxytocin (24 IU) on Pavlovian fear conditioning. We found that the peptide strengthened conditioning on both the behavioral and neural levels. Specifically, subjects exhibited faster task-related responses and enhanced SCRs to fear-associated stimuli in the late phase of conditioning, which was paralleled by heightened activity in cingulate cortex subregions in the absence of changes in amygdala function. This speaks against amygdalocentric views of oxytocin having pure anxiolytic-like effects. Instead, it suggests that the peptide enables extremely rapid and flexible adaptation to fear signals in social contexts, which may confer clear evolutionary advantages but could also elevate vulnerability for the pathological sequelae of interpersonal trauma. PMID- 26272051 TI - 5alpha-Reductase Inhibition Prevents the Luteal Phase Increase in Plasma Allopregnanolone Levels and Mitigates Symptoms in Women with Premenstrual Dysphoric Disorder. AB - Changes in neurosteroid levels during the luteal phase of the menstrual cycle may precipitate affective symptoms. To test this hypothesis, we stabilized neurosteroid levels by administering the 5alpha-reductase inhibitor dutasteride to block conversion of progesterone to its neurosteroid metabolite allopregnanolone in women with premenstrual dysphoric disorder (PMDD) and in asymptomatic control women. Sixteen women with prospectively confirmed PMDD and 16 control women participated in one of two separate randomized, double-blind, placebo-controlled, cross-over trials, each lasting three menstrual cycles. After one menstrual cycle of single-blind placebo, participants were randomized to receive, for the next two menstrual cycles, either double-blind placebo or dutasteride (low-dose 0.5 mg/day in the first eight PMDD and eight control women or high-dose 2.5 mg/day in the second group of women). All women completed the daily rating form (DRF) and were evaluated in clinic during the follicular and luteal phases of each menstrual cycle. Main outcome measures were the DRF symptoms of irritability, sadness, and anxiety. Analyses were performed with SAS PROC MIXED. In the low-dose group, no significant effect of dutasteride on PMDD symptoms was observed compared with placebo (ie, symptom cyclicity maintained), and plasma allopregnanolone levels increased in women with PMDD from follicular to the luteal phases, suggesting the absence of effect of the low-dose dutasteride on 5alpha-reductase. In contrast, the high-dose group experienced a statistically significant reduction in several core PMDD symptoms (ie, irritability, sadness, anxiety, food cravings, and bloating) on dutasteride compared with placebo. Dutasteride had no effect on mood in controls. Stabilization of allopregnanolone levels from the follicular to the luteal phase of the menstrual cycle by blocking the conversion of progesterone to its 5alpha reduced neurosteroid metabolite mitigates symptoms in PMDD. These data provide preliminary support for the pathophysiologic relevance of neurosteroids in this condition. PMID- 26272052 TI - Urban spring phenology in the middle temperate zone of China: dynamics and influence factors. AB - Urbanization and its resultant urban heat island provide a means for evaluating the impact of climate warming on vegetation phenology. To predict the possible response of vegetation phenology to rise of temperature, it is necessary to investigate factors influencing vegetation phenology in different climate zones. The start of growing season (SOS) in seven cities located in the middle temperate humid, semi-humid, semi-arid, and arid climate zones in China was extracted based on satellite-derived normalized difference vegetation index (NDVI) data. The dynamics of urban SOS from 2000 to 2009 and the correlations between urban SOS and land surface temperatures (LST), precipitation, and sunshine duration, respectively, were analyzed. The results showed that there were no obvious change trends for urban SOS, and the heat island induced by urbanization can make SOS earlier in urban areas than that in adjacent rural areas. And the impact of altitude on SOS was also not negligible in regions with obvious altitude difference between urban and adjacent rural areas. Precipitation and temperature were two main natural factors influencing urban SOS in the middle temperate zone, but their impacts varied with climate zones. Only in Harbin city with lower sunshine duration in spring, sunshine duration had more significant impact than temperature and precipitation. Interference of human activities on urban vegetation was non-negligible, which can lower the dependence of urban SOS on natural climatic factors. PMID- 26272053 TI - Evolutionary conservation analysis between the essential and nonessential genes in bacterial genomes. AB - Essential genes are thought to be critical for the survival of the organisms under certain circumstances, and the natural selection acting on essential genes is expected to be stricter than on nonessential ones. Up to now, essential genes have been identified in approximately thirty bacterial organisms by experimental methods. In this paper, we performed a comprehensive comparison between the essential and nonessential genes in the genomes of 23 bacterial species based on the Ka/Ks ratio, and found that essential genes are more evolutionarily conserved than nonessential genes in most of the bacteria examined. Furthermore, we also analyzed the conservation by functional clusters with the clusters of orthologous groups (COGs), and found that the essential genes in the functional categories of G (Carbohydrate transport and metabolism), H (Coenzyme transport and metabolism), I (Transcription), J (Translation, ribosomal structure and biogenesis), K (Lipid transport and metabolism) and L (Replication, recombination and repair) tend to be more evolutionarily conserved than the corresponding nonessential genes in bacteria. The results suggest that the essential genes in these subcategories are subject to stronger selective pressure than the nonessential genes, and therefore, provide more insights of the evolutionary conservation for the essential and nonessential genes in complex biological processes. PMID- 26272054 TI - Genetic characterization of three qnrS1-harbouring multidrug-resistance plasmids and qnrS1-containing transposons circulating in Ho Chi Minh City, Vietnam. AB - Plasmid-mediated quinolone resistance (PMQR) refers to a family of closely related genes that confer decreased susceptibility to fluoroquinolones. PMQR genes are generally associated with integrons and/or plasmids that carry additional antimicrobial resistance genes active against a range of antimicrobials. In Ho Chi Minh City (HCMC), Vietnam, we have previously shown a high frequency of PMQR genes within commensal Enterobacteriaceae. However, there are limited available sequence data detailing the genetic context in which the PMQR genes reside, and a lack of understanding of how these genes spread across the Enterobacteriaceae. Here, we aimed to determine the genetic background facilitating the spread and maintenance of qnrS1, the dominant PMQR gene circulating in HCMC. We sequenced three qnrS1-carrying plasmids in their entirety to understand the genetic context of these qnrS1-embedded plasmids and also the association of qnrS1-mediated quinolone resistance with other antimicrobial resistance phenotypes. Annotation of the three qnrS1-containing plasmids revealed a qnrS1-containing transposon with a closely related structure. We screened 112 qnrS1-positive commensal Enterobacteriaceae isolated in the community and in a hospital in HCMC to detect the common transposon structure. We found the same transposon structure to be present in 71.4 % (45/63) of qnrS1-positive hospital isolates and in 36.7 % (18/49) of qnrS1-positive isolates from the community. The resulting sequence analysis of the qnrS1 environment suggested that qnrS1 genes are widely distributed and are mobilized on elements with a common genetic background. Our data add additional insight into mechanisms that facilitate resistance to multiple antimicrobials in Gram-negative bacteria in Vietnam. PMID- 26272055 TI - Wide mutation spectrum and frequent variant Ala27Thr of FBN1 identified in a large cohort of Chinese patients with sporadic TAAD. AB - Genetic etiology in majority of patients with sporadic thoracic aortic aneurysm and dissections (STAAD) remains unknown. Recent GWAS study suggested common variant(s) in FBN1 is associated with STAAD. The present study aims to test this hypothesis and to identify mutation spectrum by targeted exome sequencing of the FBN1 gene in 146 unrelated patients with STAAD. Totally, 15.75% of FBN1 variants in STAAD were identified, including 5 disruptive and 18 missense mutations. Most of the variants were novel. Genotype-phenotype correlation analysis suggested that the maximum aortic diameter in the disruptive mutation group was significantly larger than that in the non-Cys missense mutation group. Interestingly, the variant Ala27Thr at -1 position, which is predicted to change the cleavage site of the signal peptidase of fibrillin-1, was detected in two unrelated patients. Furthermore, genotyping analysis of this variant detected 10 heterozygous Ala27Thr from additional 666 unrelated patients (1.50%), versus 7 from 1500 controls (0.47%), indicating a significant association of this variant with STAAD. Collectively, the identification of the variant Ala27Thr may represent a relatively common genetic predisposition and a novel pathogenetic mechanism for STAAD. Also, expansion of the mutation spectrum in FBN1 will be helpful in genetic counselling for Chinese patients with STAAD. PMID- 26272056 TI - Transcriptional Regulation of the Pancreatic Islet: Implications for Islet Function. AB - Islets of Langerhans contain multiple hormone-producing endocrine cells controlling glucose homeostasis. Transcription establishes and maintains islet cellular fates and identities. Genetic and environmental disruption of islet transcription triggers cellular dysfunction and disease. Early transcriptional regulation studies of specific islet genes, including insulin (INS) and the transcription factor PDX1, identified the first cis-regulatory DNA sequences and trans-acting factors governing islet function. Here, we review how human islet "omics" studies are reshaping our understanding of transcriptional regulation in islet (dys)function and diabetes. First, we highlight the expansion of islet transcript number, form, and function and of DNA transcriptional regulatory elements controlling their production. Next, we cover islet transcriptional effects of genetic and environmental perturbation. Finally, we discuss how these studies' emerging insights should empower our diabetes research community to build mechanistic understanding of diabetes pathophysiology and to equip clinicians with tailored, precision medicine options to prevent and treat islet dysfunction and diabetes. PMID- 26272057 TI - The prevalence of severe fatigue in rheumatic diseases: an international study. AB - Fatigue is a common, disabling, and difficult-to-manage problem in rheumatic diseases. Prevalence estimates of fatigue within rheumatic diseases vary considerably. Data on the prevalence of severe fatigue across multiple rheumatic diseases using a similar instrument is missing. Our aim was to provide an overview of the prevalence of severe fatigue across a broad range of rheumatic diseases and to examine its association with clinical and demographic variables. Online questionnaires were filled out by an international sample of 6120 patients (88 % female, mean age 47) encompassing 30 different rheumatic diseases. Fatigue was measured with the RAND(SF)-36 Vitality scale. A score of <=35 was taken as representing severe fatigue (90 % sensitivity and 81 % specificity for chronic fatigue syndrome). Severe fatigue was present in 41 to 57 % of patients with a single inflammatory rheumatic disease such as rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, Sjogren's syndrome, psoriatic arthritis, and scleroderma. Severe fatigue was least prevalent in patients with osteoarthritis (35 %) and most prevalent in patients with fibromyalgia (82 %). In logistic regression analysis, severe fatigue was associated with having fibromyalgia, having multiple rheumatic diseases without fibromyalgia, younger age, lower education, and language (French: highest prevalence; Dutch: lowest prevalence). In conclusion, one out of every two patients with a rheumatic disease is severely fatigued. As severe fatigue is detrimental to the patient, the near environment, and society at large, unraveling the underlying mechanisms of fatigue and developing optimal treatment should be top priorities in rheumatologic research and practice. PMID- 26272058 TI - Views on clinically suspect arthralgia: a focus group study. AB - The rheumatology field is moving towards identifying individuals with an increased risk for rheumatoid arthritis (RA) at a stage when arthritis is still absent but persons having clinically suspect arthralgia (CSA). Incorporating patients' views in rheumatologic care is pivotal; however, the views of persons with CSA on their condition are unknown. We aimed to help fill this gap by exploring illness perceptions of persons with CSA and their views on hypothetical prognoses for developing RA. Persons with CSA were invited to participate in a semi-structured focus group discussion. Illness perceptions according to the Common Sense Model (CSM) and four a priori formulated themes were explored in detail during the group discussion. The discussion was audio-taped and transcribed verbatim. Transcripts were analysed in an interpretative phenomenological approach manner, on the basis of the dimensions of the CSM by three researchers independently. The views of four participants with CSA were explored during one focus group discussion. Four dimensions of the CSM were mainly observed: Identity, Consequences, Personal Control and Concern. None of the patients identified themselves as being a patient. They did experience pain and impairments in daily functioning and were concerned that their symptoms would progress. In the absence of physician-initiated treatment, some patients changed lifestyle in order to reduce pain and to promote health. Patients unanimously said that they could not interpret prognostic information on RA development expressed in hypothetical chances. Persons with CSA do not consider themselves patients. Prognostic information related to the development of RA based on risk percentages was considered as not useful by persons with CSA. Understanding of the illness perceptions of persons with CSA by health care professionals might improve medical management and facilitate shared decision-making. PMID- 26272059 TI - Effects of plasma rich in growth factors (PRGF) on biomechanical properties of Achilles tendon repair. AB - PURPOSE: To assess the biomechanical effects of intra-tendinous injections of PRGF on the healing Achilles tendon after repair in a sheep model. METHODS: Thirty sheep were randomly assigned into one of the six groups depending on the type of treatment received (PRGF or placebo) and survival time (2, 4 and 8 weeks). The Achilles tendon injury was repaired by suturing the tendinous edges employing a three-loop pulley pattern. A trans-articular external fixation system was then used for immobilization. The PRGF or placebo was administered on a weekly basis completing a maximum of three infiltrations. The force, section and tension values were compared between the operated and healthy Achilles tendons across all groups. RESULTS: The PRGF-treated tendons had higher force at 8 weeks compared with the placebo group (p = 0.007). Between 2 and 4 weeks, a significant increase in force in both the PRGF-treated tendon (p = 0.0027) and placebo group (p = 0.0095) occurred. No significant differences were found for section ratio between PRGF-treated tendons and the placebo group for any of the time periods evaluated. At 2 weeks, PRGF-treated tendons had higher tension ratio compared with placebo group tendons (p = 0.0143). Both PRGF and placebo treatments significantly improved the force (p < 0.001 and p = 0.0095, respectively) and tension (p = 0.009 and p = 0.0039, respectively) ratios at 8 weeks compared with 2 weeks. CONCLUSION: The application of PRGF increases Achilles tendon repair strength at 8 weeks compared with the use of placebo. The use of PRGF does not modify section and tension ratios compared with placebo at 8 weeks. The tension ratio progressively increases between 2 and 8 weeks compared with the placebo. PMID- 26272060 TI - Converting round tendons to flat tendon constructs: Does the preparation process have an influence on the structural properties? AB - PURPOSE: The structural properties of hamstring tendon grafts were evaluated in a porcine model, after processing it to a flat shape, to better replace or augment anatomic flat structures (e.g. ACL, MPFL or MCL). METHODS: In this biomechanical study, porcine flexor tendons were used which have a comparable shape to semitendinosus and gracilis tendons. One part of the tendon was prepared to a flat tendon construct by splitting the tendon longitudinally with a knife to half of the diameter of the tendon. The semi-split tendon was scratched out to a flat shape. The other matched part was tested in its original round shape. The tendons (n = 40) have been fixed in a uniaxial testing machine (Zwick/Roell) by cryo clamps after preparing the fixed ends by 2-0 polyester sutures (2-0 Ethibond(r) EXCEL, Ethicon, Somerville, NJ). In every specimen, there was a free 60-mm tendon part between both clamps. The tendons have been loaded to failure to evaluate typical biomechanical parameters such as stiffness, yield load and maximum load. RESULTS: No statistically significant differences (n.s.) regarding stiffness, yield load and maximum load between natively round and processed flat tendons could be detected. CONCLUSION: A prepared flat-shaped tendon does not show any different structural properties compared with an original round tendon. Therefore, a flat tendon seems to be a biomechanical stable graft option for anatomic reconstruction or augmentation of injured natively flat-shaped structures such as MCL, MPFL or ACL. PMID- 26272061 TI - The results of two-stage revision TKA using Ceftazidime-Vancomycin-impregnated cement articulating spacers in Tsukayama Type II periprosthetic joint infections. AB - PURPOSE: This study examined the success and factors associated with failure, of using cement spacers impregnated with high-dose Ceftazidime and Vancomycin when performing two-stage revision for infected total knee arthroplasty (TKA). METHODS: A retrospective analysis was performed using a prospectively collected database of 82 patients (median age 68 years, range 39-87) with a confirmed deep TKA infection treated with a two-stage revision. All cement spacers were impregnated with high-dose Ceftazidime and Vancomycin. The rate of success was recorded-an association between failure of treatment, and patient factors, previous surgical treatment, and microbial characteristics was sought. RESULTS: The mean time to infection from index arthroplasty was 45 months (range 3-240). The initial two-stage revision was successful in 70/82 patients (85.4 %), who remained free of infection at average follow-up of 36.2 months (range 24-85). A second two-stage revision for infection was required in 12/82 patients (14.6 %), which was successful in 4/12 (33 %). A third two-stage revision was performed in three patients, all of whom had a polymicrobial infection of which only one patient had successful eradication of infection. Recurrent infection was correlated with irrigation and debridement with implant retention prior to initial two-stage revision (p < 0.01), polymicrobial infections (p = 0.035), and infections presenting <6 months after index surgery (p = 0.031). No correlation was seen with age, BMI, type of organism, diabetes mellitus, or Charlson Comorbidity Index. CONCLUSION: The findings of this study suggest that the combination of Ceftazidime and Vancomycin in cement spacers is as efficacious as other published single or combined antibiotic mixtures, which is clinically relevant to clinicians treating this difficult problem in the setting of patients with compromised renal function. PMID- 26272062 TI - Integrating Murine and Clinical Trials with Cabozantinib to Understand Roles of MET and VEGFR2 as Targets for Growth Inhibition of Prostate Cancer. AB - PURPOSE: We performed parallel investigations in cabozantinib-treated patients in a phase II trial and simultaneously in patient-derived xenograft (PDX) models to better understand the roles of MET and VEGFR2 as targets for prostate cancer therapy. EXPERIMENTAL DESIGN: In the clinical trial, radiographic imaging and serum markers were examined, as well as molecular markers in tumors from bone biopsies. In mice harboring PDX intrafemurally or subcutaneously, cabozantinib effects on tumor growth, MET, PDX in which MET was silenced, VEGFR2, bone turnover, angiogenesis, and resistance were examined. RESULTS: In responsive patients and PDX, islets of viable pMET-positive tumor cells persisted, which rapidly regrew after drug withdrawal. Knockdown of MET in PDX did not affect tumor growth in mice nor did it affect cabozantinib-induced growth inhibition but did lead to induction of FGFR1. Inhibition of VEGFR2 and MET in endothelial cells reduced the vasculature, leading to necrosis. However, each islet of viable cells surrounded a VEGFR2-negative vessel. Reduction of bone turnover was observed in both cohorts. CONCLUSIONS: Our studies demonstrate that MET in tumor cells is not a persistent therapeutic target for metastatic castrate-resistant prostate cancer (CRPC), but inhibition of VEGFR2 and MET in endothelial cells and direct effects on osteoblasts are responsible for cabozantinib-induced tumor inhibition. However, vascular heterogeneity represents one source of primary therapy resistance, whereas induction of FGFR1 in tumor cells suggests a potential mechanism of acquired resistance. Thus, integrated cross-species investigations demonstrate the power of combining preclinical models with clinical trials to understand mechanisms of activity and resistance of investigational agents. PMID- 26272063 TI - MEK plus PI3K/mTORC1/2 Therapeutic Efficacy Is Impacted by TP53 Mutation in Preclinical Models of Colorectal Cancer. AB - PURPOSE: PI3K pathway activation occurs in concomitance with RAS/BRAF mutations in colorectal cancer, limiting the sensitivity to targeted therapies. Several clinical studies are being conducted to test the tolerability and clinical activity of dual MEK and PI3K pathway blockade in solid tumors. EXPERIMENTAL DESIGN: In the present study, we explored the efficacy of dual pathway blockade in colorectal cancer preclinical models harboring concomitant activation of the ERK and PI3K pathways. Moreover, we investigated if TP53 mutation affects the response to this therapy. RESULTS: Dual MEK and mTORC1/2 blockade resulted in synergistic antiproliferative effects in cell lines bearing alterations in KRAS/BRAF and PIK3CA/PTEN. Although the on-treatment cell-cycle effects were not affected by the TP53 status, a marked proapoptotic response to therapy was observed exclusively in wild-type TP53 colorectal cancer models. We further interrogated two independent panels of KRAS/BRAF- and PIK3CA/PTEN-altered cell line- and patient-derived tumor xenografts for the antitumor response toward this combination of agents. A combination response that resulted in substantial antitumor activity was exclusively observed among the wild-type TP53 models (two out of five, 40%), but there was no such response across the eight mutant TP53 models (0%). Interestingly, within a cohort of 14 patients with colorectal cancer treated with these agents for their metastatic disease, two patients with long lasting responses (32 weeks) had TP53 wild-type tumors. CONCLUSIONS: Our data support that, in wild-type TP53 colorectal cancer cells with ERK and PI3K pathway alterations, MEK blockade results in potent p21 induction, preventing apoptosis to occur. In turn, mTORC1/2 inhibition blocks MEK inhibitor-mediated p21 induction, unleashing apoptosis. Clin Cancer Res; 21(24); 5499-510. (c)2015 AACR. PMID- 26272064 TI - Raman Spectroscopy of Experimental Oral Carcinogenesis: Study on Sequential Cancer Progression in Hamster Buccal Pouch Model. AB - Oral cancers suffer from poor 5-year survival rates, owing to late detection of the disease. Current diagnostic/screening tools need to be upgraded in view of disadvantages like invasiveness, tedious sample preparation, long output times, and interobserver variances. Raman spectroscopy has been shown to identify many disease conditions, including oral cancers, from healthy conditions. Further studies in exploring sequential changes in oral carcinogenesis are warranted. In this Raman spectroscopy study, sequential progression in experimental oral carcinogenesis in Hamster buccal pouch model was investigated using 3 approaches ex vivo, in vivo sequential, and in vivo follow-up. In all these studies, spectral changes show lipid dominance in early stages while later stages and tumors showed increased protein to lipid ratio and nucleic acids. On similar lines, early weeks of 7,12-dimethylbenz(a)anthracene-treated and control groups showed higher overlap and low classification. The classification efficiency increased progressively, reached a plateau phase and subsequently increased up to 100% by 14 weeks. The misclassifications between treated and control spectra suggested some changes in controls as well, which was confirmed by a careful reexamination of histopathological slides. These findings suggests Raman spectroscopy may be able to identify microheterogeneity, which may often go unnoticed in conventional biochemistry wherein tissue extracts are employed, as well as in histopathology. In vivo findings, quite comparable to gold-standard supported ex vivo findings, give further proof of Raman spectroscopy being a promising label-free, noninvasive diagnostic adjunct for future clinical applications. PMID- 26272065 TI - Effect of temperature and diet on wound healing in Atlantic salmon (Salmo salar L.). AB - Compromised skin integrity of farmed Atlantic salmon, commonly occurring under low temperature and stressful conditions, has major impacts on animal welfare and economic productivity. Even fish with minimal scale loss and minor wounds can suffer from secondary infections, causing downgrading and mortalities. Wound healing is a complex process, where water temperature and nutrition play key roles. In this study, Atlantic salmon (260 g) were held at different water temperatures (4 or 12 degrees C) and fed three different diets for 10 weeks, before artificial wounds were inflicted and the wound healing process monitored for 2 weeks. The fish were fed either a control diet, a diet supplemented with zinc (Zn) or a diet containing a combination of functional ingredients in addition to Zn. The effect of diet was assessed through subjective and quantitative skin histology and the transcription of skin-associated chemokines. Histology confirmed that wound healing was faster at 12 degrees C. The epidermis was more organised, and image analyses of digitised skin slides showed that fish fed diets with added Zn had a significantly larger area of the epidermis covered by mucous cells in the deeper layers after 2 weeks, representing more advanced healing progression. Constitutive levels of the newly described chemokines, herein named CK 11A, B and C, confirmed their preferential expression in skin compared to other tissues. Contrasting modulation profiles at 4 and 12 degrees C were seen for all three chemokines during the wound healing time course, while the Zn-supplemented diets significantly increased the expression of CK 11A and B during the first 24 h of the healing phase. PMID- 26272066 TI - Peptide self-assembly for nanomaterials: the old new kid on the block. AB - Peptide self-assembly is an increasingly attractive tool for nanomaterials. Perfected in biology peptide self-assembling systems have impacted on nearly any conceivable nanomaterial type. However, with all the information available to us commercialisation of peptide materials remains in its infancy. In an attempt to better understand the reasons behind this shortcoming we categorise peptide self assembled materials in relation to their non-peptide counterparts. A particular emphasis is placed on the versatility of peptide self-assembly in terms of modularity, responsiveness and functional diversity, which enables direct comparisons with more traditional material chemistries. PMID- 26272067 TI - The use of intermittent preventive treatment in pregnancy and insecticide-treated bed nets for malaria prevention by women of child-bearing age in eight districts in Malawi. AB - BACKGROUND: Intermittent preventive treatment in pregnancy (IPTp) and insecticide treated bed nets (ITNs) can reduce the morbidity and mortality associated with malaria in pregnancy. Although the coverage for both IPTp and ITN use have been described in Malawi, the analysis of factors associated with IPTp receipt and ITN use is lacking. This analysis was conducted to assess IPTp and ITN use and predictors of use by women of child-bearing age (WOCBA). METHODS: A two-stage cluster-sample cross-sectional survey was conducted April 16-30, 2009 in eight districts across Malawi. Information on receipt of two or more doses of IPTp, ITN ownership, and ITN use the night before the survey was collected. Multivariate logistic regression was used to assess predictors of IPTp and ITN use. RESULTS: Data were collected from 7407 households containing 6985 WOCBA and 3213 recently pregnant women (women who reported a completed pregnancy in the 2 years before the survey). Most recently pregnant women (96 %) had at least one antenatal care (ANC) clinic visit; 91 % reported receiving at least one dose of IPTp, and 72 % reported receiving two or more doses of IPTp. Women in Phalombe, Rumphi, and Lilongwe were more likely to receive two doses of IPTp than those in Blantyre [adjusted odds ratio (aOR) 2.5 (95 % CI 1.5-4.5), 2.5 (95 % CI 1.5-4.3), and 2.0 (95 % CI 1.2-3.1), respectively]. Educated women were more likely to have received IPTp compared to women with no education [aOR 1.6 (95 % CI 1.0-2.6) for those who completed primary school, aOR1.9 (95 % CI 1.1-3.3) for some secondary school, and aOR 4.1 (95 % CI 1.9-8.7) for completed secondary school or above], and women in the poorest socioeconomic status quintile were less likely to receive IPTp than those in the least poor quintile [aOR 0.68 (95 % CI 0.48 0.97)]. In all, 53 % of WOCBA used an ITN the previous night. Women in Nkhotkhota and Phalombe were less likely to have slept under an ITN the previous night compared to those in Blantyre [aOR 0.52 (95 % CI 0.39-0.69) and aOR 0.67 (95 % CI 0.47-0.95), respectively]. In addition, age [aOR 0.61 (95 % CI 0.45-0.83) for women 15-19 years old], and either being currently pregnant [aOR 1.5 (95 % CI 1.2 2.0)] or having been pregnant in the previous 2 years [aOR 2.4, (95 % CI 2.1 2.8)] were associated with ITN use. CONCLUSION: In Malawi in 2009, IPTp and ITN use in WOCBA fell short of national and international goals. Adoption of new guidelines encouraging administration of IPTp at every scheduled ANC visit might increase IPTp use. Increasing health promotion activities to encourage earlier attendance at ANC clinics and create demand for IPTp and ITNs might improve overall IPTp and ITN use. PMID- 26272069 TI - Early severe impairment of hematopoietic stem and progenitor cells from the bone marrow caused by CLP sepsis and endotoxemia in a humanized mice model. AB - INTRODUCTION: An effective immune response to severe bacterial infections requires a robust production of the innate immunity cells from hematopoietic stem and progenitor cells (HSPCs) in a process called emergency myelopoiesis. In sepsis, an altered immune response that leads to a failure of bacterial clearance is often observed. In this study, we aimed to evaluate the impact of sepsis on human HSPCs in the bone marrow (BM) microenvironment of humanized mice subjected to acute endotoxemia and polymicrobial sepsis. METHODS: Humanized mice (hu-NSG) were generated by transplanting NOD.Cg-Prkdc/scidIL2rgamma (NSG) mice with the human cord blood CD34(+) cells. Eight weeks after the transplantation, hu-NSG mice were subjected to sepsis induced by endotoxemia-Escherichia coli lipopolysaccharide (LPS)-or by cecal ligation and puncture (CLP). Twenty-four hours later, HSPCs from BM were analyzed by flow cytometry and colony-forming unit (CFU) assay. CLP after inhibition of Notch signaling was also performed. The effects of LPS on the in vitro proliferation of CD34(+) cells from human BM were tested by CellTrace Violet dye staining. RESULTS: The expression of Toll-like receptor 4 receptor was present among engrafted human HSPCs. Both CLP and endotoxemia decreased (by 43 % and 37 %) cellularity of the BM. In addition, in both models, accumulation of early CD34(+) CD38(-) HSCs was observed, but the number of CD34(+) CD38(+) progenitors decreased. After CLP, there was a 1.5-fold increase of proliferating CD34(+) CD38(-)Ki-67(+) cells. Moreover, CFU assay revealed a depressed (by 75 % after LPS and by 50 % after CLP) production of human hematopoietic colonies from the BM of septic mice. In contrast, in vitro LPS stimulated differentiation of CD34(+) CD38(-) HSCs but did not induce proliferation of these cells in contrast to the CD34(+) CD38(+) progenitors. CLP sepsis modulated the BM microenvironment by upregulation of Jagged-1 expression on non-hematopoietic cells, and the proliferation of HSCs was Notch-dependent. CONCLUSIONS: CLP sepsis and endotoxemia induced a similar expansion and proliferation of early HSCs in the BM, while committed progenitors decreased. It is suggestive that the Notch pathway contributed to this effect. Targeting early hematopoiesis may be considered as a viable alternative in the existing arsenal of supportive therapies in sepsis. PMID- 26272071 TI - Molecular aspects and chemoprevention of dimethylaminoazobenzene-induced hepatocarcinogenesis: A review. AB - The lipophilic azo dye dimethylaminoazobenzene (DAB) is a potent hepatocarcinogen accounted as a group-2B carcinogen causing risk to humans. DAB is commonly used as a coloring agent in food, pharmaceuticals, beverages, soap and polishes. The exploration of DAB-induced hepatocarcinogenesis in animal models helped to an extent to perceive the histological, biochemical and molecular mechanisms of DAB carcinogenesis and also the severity of DAB exposure to humans. In experimental animal models, it is well-proved that the procarcinogen DAB is predominantly metabolized by cytochrome P450 enzymes giving rise to the formation of toxic electrophiles and reactive oxygen species (ROS), which further forms DNA adducts leading to the development of hepatic tumors. Recently, research evidence suggests that dietary phytochemicals and plant polyphenols are promising agents to control the incidence of DAB-induced hepatocarcinogenesis by preventing the generation of toxic electrophiles and ROS thereby inhibiting the formation of DNA adducts. This review highlights the role of specific dietary factors, biotransformation of DAB, phenotypic and genotypic alterations, and significance of certain chemopreventive agents against DAB-induced hepatocarcinogenesis. PMID- 26272068 TI - Transcriptome analysis of the Holly mangrove Acanthus ilicifolius and its terrestrial relative, Acanthus leucostachyus, provides insights into adaptation to intertidal zones. AB - BACKGROUND: Acanthus is a unique genus consisting of both true mangrove and terrestrial species; thus, it represents an ideal system for studying the origin and adaptive evolution of mangrove plants to intertidal environments. However, little is known regarding the two respects of mangrove species in Acanthus. In this study, we sequenced the transcriptomes of the pooled roots and leaves tissues for a mangrove species, Acanthus ilicifolius, and its terrestrial congener, A. leucostachyus, to illustrate the origin of the mangrove species in this genus and their adaptive evolution to harsh habitats. RESULTS: We obtained 73,039 and 69,580 contigs with N50 values of 741 and 1557 bp for A. ilicifolius and A. leucostachyus, respectively. Phylogenetic analyses based on four nuclear segments and three chloroplast fragments revealed that mangroves and terrestrial species in Acanthus fell into different clades, indicating a single origin of the mangrove species in Acanthus. Based on 6634 orthologs, A. ilicifolius and A. leucostachyus were found to be highly divergent, with a peak of synonymous substitution rate (Ks) distribution of 0.145 and an estimated divergence time of approximately 16.8 million years ago (MYA). The transgression in the Early to Middle Miocene may be the major reason for the entry of the mangrove lineage of Acanthus into intertidal environments. Gene ontology (GO) classifications of the full transcriptomes did not show any apparent differences between A. ilicifolius and A. leucostachyus, suggesting the absence of gene components specific to the mangrove transcriptomes. A total of 99 genes in A. ilicifolius were identified with signals of positive selection. Twenty-three of the 99 positively selected genes (PSGs) were found to be involved in salt, heat and ultraviolet stress tolerance, seed germination and embryo development under periodic inundation. These stress-tolerance related PSGs may be crucial for the adaptation of the mangrove species in this genus to stressful marine environments and may contribute to speciation in Acanthus. CONCLUSIONS: We characterized the transcriptomes of one mangrove species of Acanthus, A. ilicifolius, and its terrestrial relative, A. leucostachyus, and provided insights into the origin of the mangrove Acanthus species and their adaptive evolution to abiotic stresses in intertidal environments. PMID- 26272070 TI - Seasonal variations in mortality and clinical indicators in international hemodialysis populations from the MONDO registry. AB - BACKGROUND: Seasonal mortality differences have been reported in US hemodialysis (HD) patients. Here we examine the effect of seasons on mortality, clinical and laboratory parameters on a global scale. METHODS: Databases from the international Monitoring Dialysis Outcomes (MONDO) consortium were queried to identify patients who received in-center HD for at least 1 year. Clinics were stratified by hemisphere and climate zone (tropical or temperate). We recorded mortality and computed averages of pre-dialysis systolic blood pressure (pre SBP), interdialytic weight gain (IDWG), serum albumin, and log C-reactive protein (CRP). We explored seasonal effects using cosinor analysis and adjusted linear mixed models globally, and after stratification. RESULTS: Data from 87,399 patients were included (northern temperate: 63,671; northern tropical: 7,159; southern temperate: 13,917; southern tropical: 2,652 patients). Globally, mortality was highest in winter. Following stratification, mortality was significantly lower in spring and summer compared to winter in temperate, but not in tropical zones. Globally, pre-SBP and IDWG were lower in summer and spring as compared to winter, although less pronounced in tropical zones. Except for southern temperate zone, serum albumin levels were higher in winter. CRP levels were highest in winter. CONCLUSION: Significant global seasonal variations in mortality, pre-SBP, IDWG, albumin and CRP were observed. Seasonal variations in mortality were most pronounced in temperate climate zones. PMID- 26272073 TI - Measurement of anti-drug antibodies to biologic drugs. PMID- 26272072 TI - An Immunochip-based interaction study of contrasting interaction effects with smoking in ACPA-positive versus ACPA-negative rheumatoid arthritis. AB - OBJECTIVE: To investigate the gene-environment interaction between smoking and single nucleotide polymorphisms (SNPs), using Immunochip material, on the risk of developing either of two serologically defined subsets of RA. METHODS: Interaction between smoking and 133,648 genetic markers from the Immunochip was examined for two RA subsets, defined by the presence or absence of ACPA. A total of 1590 ACPA-positive and 891 ACPA-negative cases were compared with 1856 controls in the Swedish Epidemiological Investigation of RA (EIRA) case-control study. Logistic regression models were used to determine the presence of interaction. The proportion attributable to interaction was calculated for each smoking-SNP pair. Replication was carried out in an independent dataset from northern Sweden. To further validate and extend the results, interaction analysis was also performed using genome-wide association studies data on EIRA individuals. RESULTS: In ACPA-positive RA, 102 SNPs interacted significantly with smoking, after Bonferroni correction. All 102 SNPs were located in the HLA region, mainly within the HLA class II region, 51 of which were replicated. No additional loci outside chromosome 6 were identified in the genome-wide association studies validation. After adjusting for HLA-DRB1 shared epitope, 15 smoking-SNP pairs remained significant for ACPA-positive RA, with 8 of these replicated (loci: BTNL2, HLA-DRA, HLA-DRB5, HLA-DQA1, HLA-DOB and TAP2). For ACPA negative RA, no smoking-SNP pairs passed the threshold for significance. CONCLUSION: Our study presents extended gene variation patterns involved in gene smoking interaction in ACPA-positive, but not ACPA-negative, RA. Notably, variants in HLA-DRB1 and those in additional genes within the MHC class II region, but not in any other gene regions, showed interaction with smoking. PMID- 26272074 TI - Does hepatic hilum morphology influence long-term prognosis in type I/I cyst biliary atresia? AB - PURPOSE: Some patients with cystic biliary atresia (BA) achieve exceptionally good postoperative courses. Early differentiation of pediatric patients with the favorable-type disease can lead to beneficial long-term postoperative management. We examined whether the hepatic hilum morphology affects long-term prognosis in type I/I cyst BA, atresia of the common bile duct with/without a cyst. METHODS: Of 253 BA patients identified since 1972, 40 were classified as having type I/I cysts and were divided into two subtypes according to hepatic duct size (subtype alpha: n = 18; duct diameter, >= 1 mm and subtype beta: n = 22; duct diameter, <1 mm) to compare postoperative clinical courses. RESULTS: In subtypes alpha and beta, jaundice disappeared in 16 (89 %) and 19 (86 %) patients, respectively (p = 0.81), and 13 (72 %) and 12 (55 %) survived with native livers (p = 0.18) at a mean age of 23.3 and 25.5 years, respectively (p = 0.42). CONCLUSIONS: There were no significant differences in long-term outcomes between subtypes alpha and beta, although approximately 40 % developed liver failure during the postoperative course. Thus, close long-term follow-up is essential in type I/I cysts, regardless of the hepatic hilum morphology. PMID- 26272075 TI - Severe acquired subglottic stenosis in children: analysis of clinical features and surgical outcomes based on the range of stenosis. AB - PURPOSE: The present study analyzed the clinical features and surgical outcomes of laryngotracheal reconstruction (LTR) in pediatric patients with severe acquired subglottic stenosis (SGS) based on the range of stenosis. The aim was to clarify the indications for LTR in severe acquired SGS. METHODS: The medical records of 33 pediatric patients with severe acquired SGS (Myer-Cotton grade III or IV) at our institution between January 1994 and December 2013 were retrospectively reviewed. RESULTS: Nine patients had stenosis localized at the subglottis (localized SGS), and twenty-four patients had stenosis extending to the glottis or supraglottis from the subglottis (extended SGS). 66.7 % (6/9) of localized SGS patients were intubated after infancy, and 95.8 % (22/23) of extended SGS patients were intubated in the neonatal period. The duration of intubation was significantly shorter with localized than with extended SGS. Sixteen patients underwent LTR. The operation-specific decannulation rate was 80.0 % (4/5) in the localized SGS group and 14.3 % (1/7) in the extended SGS group. CONCLUSION: The range of stenosis was affected by the period and duration of endotracheal intubation. Surgical outcomes of LTR tended to differ between localized SGS and extended SGS. LTR can be effective for localized SGS. PMID- 26272076 TI - Hepatic ductoplasty and hepaticojejunostomy to treat narrow common hepatic duct during laparoscopic surgery for choledochal cyst. AB - We describe a novel technique for laparoscopic hepatic ductoplasty and hepaticojejunostomy in choledochal cyst with a narrow common hepatic duct. After complete cyst excision, a longitudinal incision was made in the anterior wall of the narrow common hepatic duct to enlarge the anastomotic opening. Next, the anterior wall was everted, then anchored to the hepatic hilum by suturing. Anchoring of the anterior wall provided a good field of view for creating the anastomosis, and the lumen of the anastomotic region was also secured. We believe that our technique is feasible and useful when the duct size is small. PMID- 26272080 TI - Ag on Pt(111): Changes in Electronic and CO Adsorption Properties upon PtAg/Pt(111) Monolayer Surface Alloy Formation. AB - The electronic and chemical (adsorption) properties of bimetallic Ag/Pt(111) surfaces and their modification upon surface alloy formation, that is, during intermixing of Ag and Pt atoms in the top atomic layer upon annealing, were studied by X-ray photoelectron spectroscopy (XPS) and, using CO as probe molecule, by temperature-programmed desorption (TPD) and infrared reflection absorption spectroscopy (IRRAS), respectively. The surface alloys are prepared by deposition of sub-monolayer Ag amounts on a Pt(111) surface at room temperature, leading to extended Ag monolayer islands on the substrate, and subsequent annealing of these surfaces. Surface alloy formation starts at ~600-650 K, which is evidenced by core-level shifts (CLSs) of the Ag(3d5/2 ) signal. A distinct change of the CO adsorption properties is observed when going to the intermixed PtAg surface alloys. Most prominently, we find the growth of a new desorption feature at higher temperature (~550 K) in the TPD spectra upon surface alloy formation. This goes along with a shift of the COad -related IR bands to lower wave number. Surface alloy formation is almost completed after heating to 700 K. PMID- 26272077 TI - The mobilize center: an NIH big data to knowledge center to advance human movement research and improve mobility. AB - Regular physical activity helps prevent heart disease, stroke, diabetes, and other chronic diseases, yet a broad range of conditions impair mobility at great personal and societal cost. Vast amounts of data characterizing human movement are available from research labs, clinics, and millions of smartphones and wearable sensors, but integration and analysis of this large quantity of mobility data are extremely challenging. The authors have established the Mobilize Center (http://mobilize.stanford.edu) to harness these data to improve human mobility and help lay the foundation for using data science methods in biomedicine. The Center is organized around 4 data science research cores: biomechanical modeling, statistical learning, behavioral and social modeling, and integrative modeling. Important biomedical applications, such as osteoarthritis and weight management, will focus the development of new data science methods. By developing these new approaches, sharing data and validated software tools, and training thousands of researchers, the Mobilize Center will transform human movement research. PMID- 26272078 TI - Heterosexual men who patronise entertainment establishments versus brothels in an Asian urban setting - which group practises riskier sexual behaviours? AB - BACKGROUND: Sex work has shifted from brothels to entertainment establishments (EEs) in Asia. Men who patronise EEs could act as a bridging population for human immunodeficiency virus (HIV) and sexually transmitted infection (STI) transmission through unprotected sex with the female EE workers to their spouses and regular partners. The aim of this study was to compare the prevalence and factors associated with risky sexual behaviours among the heterosexual men who patronised the EEs and brothels in Singapore. METHODS: This was a cross-sectional survey involving 569 heterosexual men (297 recruited from brothels and 272 from EEs). A 2-stage sampling involving proportional stratified random sampling of the brothels and EEs, followed by time location sampling of the men, was conducted. For multivariable analysis, we used a mixed effects logistic model with backward elimination to account for clustering by venue and to obtain the adjusted odds ratio (aOR) for the association of various factors with consistent condom use in vaginal and oral sex respectively. RESULTS: Men who patronised EEs were younger, more likely to be single, more highly-educated and comprised more professionals compared to the brothel group. On multivariable analysis, consistent condom use for vaginal sex decreased at the EE setting (aOR 0.64; 95 % CI: 0.42 -0.97) and with alcohol use before sex (aOR 0.67; 95 % CI: 0.46 - 0.98) and increased with perceived high risk of getting HIV/STIs from partner (aOR 2.08; 95 % CI: 1.30 - 3.32) and partner's request for condom use (aOR 5.48; 95 % CI: 1.20 - 25.11). For consistent condom use with oral sex, this decreased at the EE setting (aOR 0.64; 95 % CI: 0.39 - 0.98) and with alcohol use before sex (aOR 0.50; 95 % CI: 0.31 - 0.81) and increased with partner's request for condom use (aOR 5.19; 95 % CI: 1.38 - 19.57). CONCLUSIONS: Men who patronised EEs practised risker sexual behaviours compared to the brothel group. Priority should be given for intervention programmes to target men who patronise EEs, which could involve the female EE workers, the EE owners as well as the managers for effective HIV/STI prevention. PMID- 26272081 TI - Maximum basal FSH predicts reproductive outcome better than cycle-specific basal FSH levels: waiting for a "better" month conveys limited retrieval benefits. AB - BACKGROUND: Elevated follicle stimulating hormone (FSH) is associated with poor vaginal oocyte retrieval (VOR) outcomes and cycle cancellations but intercycle variability in basal FSH reportedly does not predict ovarian response. METHODS: We conducted a retrospective cohort study of basal FSH (n = 15573 cycles) in couples (n = 9132) who initiated IVF cycle(s) with basal estradiol (E2) <100 pg/mL between 2002 and 2014 to reevaluate this hypothesis. The most recent (current) FSH, maximum FSH (Max FSH) and prior cycle maximum basal FSH (PMax FSH) were computed for each cycle. Metaphase II (MII) oocyte counts were modeled by age, stimulation type, prior peak E2 level, prior MII count, Max FSH, PMax FSH and current FSH. Antral follicle counts, pregnancy, clinical pregnancy and live birth rates were modeled as secondary outcomes. RESULTS: Max FSH level distinguished completed cycles from cancelled cycles better than PMax FSH or current FSH (AUC of 0.72, 0.71 and 0.61, respectively, p < 0.001). Fewer MIIs were retrieved (5.7 +/- 3.8) in cycles with Max FSH >13 mIU/mL (n = 1475) than those with <=13 mIU/mL (n = 11978) (11.6 +/- 7.1) (p < 0.001). Max FSH was a better predictor of MII count than PMax FSH or current FSH after controlling for age, stimulation type, prior peak E2 level and prior MII count. Additional MIIs were retrieved on average in cycles with PMax FSH >13 mIU/mL (n = 1930) whose current FSH was <=13 mIU/ml rather than >13 mIU/ml (p < 0.01) after controlling for age, cycle number and stimulation type. However, no improvement in pregnancy or live birth rate was detected. CONCLUSIONS: Max FSH is the best FSH-based predictor of ovarian reserve. Retrieval benefits from waiting for a "better" month appear to exist but are limited. PMID- 26272082 TI - Skeletal Muscle Vascular Control During Exercise: Impact of Nitrite Infusion During Nitric Oxide Synthase Inhibition in Healthy Rats. AB - The nitric oxide synthase (NOS)-independent pathway of nitric oxide (NO) production in which nitrite (NO2 (-)) is reduced to NO may have therapeutic applications for those with cardiovascular diseases in which the NOS pathway is downregulated. We tested the hypothesis that NO2 (-) infusion would reduce mean arterial pressure (MAP) and increase skeletal muscle blood flow (BF) and vascular conductance (VC) during exercise in the face of NOS blockade via L-NAME. Following infusion of L-NAME (10 mg kg(-1), L-NAME), male Sprague-Dawley rats (3 6 months, n = 8) exercised without N(G)-nitro-L arginine methyl ester (L-NAME) and after infusion of sodium NO2 (-) (7 mg kg(-1); L-NAME + NO2 (-)). MAP and hindlimb skeletal muscle BF (radiolabeled microsphere infusions) were measured during submaximal treadmill running (20 m min(-1), 5% grade). Across group comparisons were made with a published control data set (n = 11). Relative to L NAME, NO2 (-) infusion significantly reduced MAP (P < 0.03). The lower MAP in L NAME+NO2 (-) was not different from healthy control animals (control: 137 +/- 3 L NAME: 157 +/- 7, L-NAME + NO2 (-): 136 +/- 5 mm Hg). Also, NO2 (-) infusion significantly increased VC when compared to L-NAME (P < 0.03), ultimately negating any significant differences from control animals (control: 0.78 +/- 0.05, L-NAME: 0.57 +/- 0.03, L-NAME + NO2 (-); 0.69 +/- 0.04 mL min(-1) 100 g(-1) mm Hg(-1)) with no apparent fiber-type preferential effect. Overall, hindlimb BF was decreased significantly by L-NAME; however, in L-NAME + NO2 (-), BF improved to a level not significantly different from healthy controls (control: 108 +/- 8, L-NAME: 88 +/- 3, L-NAME + NO2 (-): 94 +/- 6 mL min(-1) 100 g(-1), P = 0.38 L NAME vs L-NAME + NO2 (-)). Individuals with diseases that impair NOS activity, and thus vascular function, may benefit from a NO2 (-)-based therapy in which NO bioavailability is elevated in an NOS-independent manner. PMID- 26272083 TI - Mitochondrial dynamics in the pathogenic mold Aspergillus fumigatus: therapeutic and evolutionary implications. AB - Mitochondria within eukaryotic cells continuously fuse and divide. This phenomenon is called mitochondrial dynamics and crucial for mitochondrial function and integrity. We performed a comprehensive analysis of mitochondrial dynamics in the pathogenic mold Aspergillus fumigatus. Phenotypic characterization of respective mutants revealed the general essentiality of mitochondrial fusion for mitochondrial genome maintenance and the mold's viability. Surprisingly, it turned out that the mitochondrial rhomboid protease Pcp1 and its processing product, s-Mgm,1 which are crucial for fusion in yeast, are dispensable for fusion, mtDNA maintenance and viability in A. fumigatus. In contrast, mitochondrial fission mutants show drastically reduced growth and sporulation rates and increased heat susceptibility. However, reliable inheritance of mitochondria to newly formed conidia is ensured. Strikingly, mitochondrial fission mutants show a significant and growth condition-dependent increase in azole resistance. Parallel disruption of fusion in a fission mutant partially rescues growth and sporulation defects and further increases the azole resistance phenotype. Taken together, our results indicate an emerging dispensability of the mitochondrial rhomboid protease function in mitochondrial fusion, the suitability of mitochondrial fusion machinery as antifungal target and the involvement of mitochondrial dynamics in azole susceptibility. PMID- 26272085 TI - Gap prepulse inhibition of the auditory late response in healthy subjects. AB - The gap-startle paradigm has been used as a behavioral method for tinnitus screening in animal studies. This study aimed to investigate gap prepulse inhibition (GPI) of the auditory late response (ALR) as the objective response of the gap-intense sound paradigm in humans. ALRs were recorded in response to gap intense and no-gap-intense sound stimuli in 27 healthy subjects. The amplitudes of the baseline-to-peak (N1, P2, and N2) and the peak-to-peak (N1P2 and P2N2) were compared between two averaged ALRs. The variations in the inhibition ratios of N1P2 and P2N2 during the experiment were analyzed by increasing stimuli repetitions. The effect of stimulus parameter adjustments on GPI ratios was evaluated. No-gap-intense sound stimuli elicited greater peak amplitudes than gap intense sound stimuli, and significant differences were found across all peaks. The overall mean inhibition ratios were significantly lower than 1.0, where the value 1.0 indicates that there were no differences between gap-intense and no-gap intense sound responses. The initial decline in GPI ratios was shown in N1P2 and P2N2 complexes, and this reduction was nearly complete after 100 stimulus repetitions. Significant effects of gap length and interstimulus interval on GPI ratios were observed. We found significant inhibition of ALR peak amplitudes in performing the gap-intense sound paradigm in healthy subjects. The N1P2 complex represented GPI well in terms of suppression degree and test-retest reliability. Our findings offer practical information for the comparative study of healthy subjects and tinnitus patients using the gap-intense sound paradigm with the ALR. PMID- 26272086 TI - Industry update: 1-30 April 2015. PMID- 26272087 TI - I-SceI-mediated double-strand DNA breaks stimulate efficient gene targeting in the industrial fungus Trichoderma reesei. AB - Targeted integration of expression cassettes for enzyme production in industrial microorganisms is desirable especially when enzyme variants are screened for improved enzymatic properties. However, currently used methods for targeted integration are inefficient and result in low transformation frequencies. In this study, we expressed the Saccharomyces cerevisiae I-SceI meganuclease to generate double-strand breaks at a defined locus in the Trichoderma reesei genome. We showed that the double-strand DNA breaks mediated by I-SceI can be efficiently repaired when an exogenous DNA cassette flanked by regions homologous to the I SceI landing locus was added during transformation. Transformation efficiencies increased approximately sixfold compared to control transformation. Analysis of the transformants obtained via I-SceI-mediated gene targeting showed that about two thirds of the transformants resulted from a homologous recombination event at the predetermined locus. Counter selection of the transformants for the loss of the pyrG marker upon integration of the DNA cassette showed that almost all of the clones contained the cassette at the predetermined locus. Analysis of independently obtained transformants using targeted integration of a glucoamylase expression cassette demonstrated that glucoamylase production among the transformants was high and showing limited variation. In conclusion, the gene targeting system developed in this study significantly increases transformation efficiency as well as homologous recombination efficiency and omits the use of Deltaku70 strains. It is also suitable for high-throughput screening of enzyme variants or gene libraries in T. reesei. PMID- 26272088 TI - Development and validation of an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the quantitative determination of rhamnolipid congeners. AB - Rhamnolipids (RLs) are synthesised as a complex mixture of congeners comprising either one or two molecules of rhamnose glycosidically linked to a dimer of 3 hydroxy fatty acids varying in chain length and degree of saturation. Currently, HPLC-MS/MS is the most precise and accurate method for RL determination, while accurate quantification is limited. In this study, a rapid ultra pressure liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the rapid and quantification of individual RL congeners. Increased RLs specificity was achieved using tandem mass spectrometry in multiple reaction monitoring (MRM) mode which was used to quantify RL isomer pairs such as Rha-Rha C8-C10/Rha-Rha-C10-C8 which are difficult to resolve chromatographically. UPLC showed an 18-fold reduction in retention time for Rha-Rha-C10-C10 (1.07 min) and a 17-fold reduction for Rha-C10-C10 (1.36), the major rhamnolipids present, compared to HPLC, with a total run time less than 2.2 min. The results show that the linear range for the main RL congeners (Rha-C10-C10 and Rha-Rha-C10-C10) is 0.1 to 100 MUg/mL. The LOD and LOQ for Rha-C10-C10 is 0.05 and 0.1 MUg/mL and for Rha-Rha-C10-C10 is 0.1 and 0.5 MUg/mL, respectively. The method was validated for linearity, intra- and inter-day precision and accuracy in accordance with FDA guidelines. The method was applied for the quantification of 14 individual RL congeners produced by Pseudomonas aeruginosa ST5 and comparison of RLs composition on four different carbon sources. Quantification of the individual congeners showed a conserved congener distribution irrespective of carbon source with a preferential selection for C10 beta-hydroxyacids as the lipid component of RLs. The only statistically significant differences detected were between actual RL yields on the various carbon sources. PMID- 26272090 TI - Lactate and glucose concomitant consumption as a self-regulated pH detoxification mechanism in HEK293 cell cultures. AB - One of the most important limitations of mammalian cell-based processes is the secretion and accumulation of lactate as a by-product of their metabolism. Among the cell lines commonly used in industrial bioprocesses, HEK293 has been gaining importance over the last years. Up recently, HEK293 cells were known to consume lactate in late stages of cell culture usually when glucose and/or glutamine were depleted from media. Remarkably, in both scenarios, no significant cell growth was reported. However, we have observed a different metabolic behavior regarding lactate production and consumption in HEK293 cultures. HEK293 cells were able to co-metabolize glucose and lactate simultaneously, even in exponentially growing cell cultures. Our deep study of the effects of environmental conditions on lactate metabolism revealed that pH was the key to trigger the metabolic shift from lactate production to lactate and glucose concomitant consumption. Remarkably, this shift could be triggered at will when pH was set at 6.8. Even more interesting was the fact that lowering pH to 6.6 and supplementing media with exogenous lactate resulted in co-consumption of glucose and lactate from the beginning of cell culture, without affecting cell growth or protein productivity. On the contrary, cell growth was clearly hampered at this low pH if extracellular lactate was lacking. From our results, we hypothesize that HEK293 cells metabolize extracellular lactate as a strategy for pH detoxification, by means of co-transporting extracellular protons together with lactate into the cytosol. This novel hypothesis for unraveling lactate metabolism in HEK293 cells could open a door to re-direct genetic engineering strategies in order to obtain more efficient cell lines and also to further develop animal cell technology applications. PMID- 26272089 TI - Irradiation of Yarrowia lipolytica NRRL YB-567 creating novel strains with enhanced ammonia and oil production on protein and carbohydrate substrates. AB - Increased interest in sustainable production of renewable diesel and other valuable bioproducts is redoubling efforts to improve economic feasibility of microbial-based oil production. Yarrowia lipolytica is capable of employing a wide variety of substrates to produce oil and valuable co-products. We irradiated Y. lipolytica NRRL YB-567 with UV-C to enhance ammonia (for fertilizer) and lipid (for biodiesel) production on low-cost protein and carbohydrate substrates. The resulting strains were screened for ammonia and oil production using color intensity of indicators on plate assays. Seven mutant strains were selected (based on ammonia assay) and further evaluated for growth rate, ammonia and oil production, soluble protein content, and morphology when grown on liver infusion medium (without sugars), and for growth on various substrates. Strains were identified among these mutants that had a faster doubling time, produced higher maximum ammonia levels (enzyme assay) and more oil (Sudan Black assay), and had higher maximum soluble protein levels (Bradford assay) than wild type. When grown on plates with substrates of interest, all mutant strains showed similar results aerobically to wild-type strain. The mutant strain with the highest oil production and the fastest doubling time was evaluated on coffee waste medium. On this medium, the strain produced 0.12 g/L ammonia and 0.20 g/L 2-phenylethanol, a valuable fragrance/flavoring, in addition to acylglycerols (oil) containing predominantly C16 and C18 residues. These mutant strains will be investigated further for potential application in commercial biodiesel production. PMID- 26272091 TI - Isolation and characterisation of non-anaerobic butanol-producing symbiotic system TSH06. AB - Butanol-producing microorganisms are all obligate anaerobes. In this study, a unique symbiotic system TSH06 was isolated to be capable of producing butanol under non-anaerobic condition. Denaturing gradient gel electrophoresis (DGGE) analysis of 16S ribosomal RNA (rRNA) revealed that two strains coexist in TSH06. The two strains were identical to Clostridium acetobutylicum and Bacillus cereus, respectively. They were isolated individually and named as C. acetobutylicum TSH1 and B. cereus TSH2. C. acetobutylicum TSH1 is a butanol-producing, obligate anaerobic strain. Facultative anaerobic B. cereus TSH2 did not possess the ability of butanol production; however, it offered C. acetobutylicum TSH1 the viability under non-anaerobic condition. Moreover, B. cereus TSH2 enhanced butanol yield and speed of fermentation. TSH06 produced 12.97 g/L butanol and 15.39 g/L total solvent under non-anaerobic condition, which is 25 and 24 %, respectively, higher than those of C. acetobutylicum TSH1. In addition, TSH06 produced butanol faster under non-anaerobic condition than under anaerobic condition. Butanol accounted for more than 80 % of total solvent, which is higher than the known report. TSH06 was stable during passage. In all, TSH06 is a promising candidate for industrialisation of biobutanol with high yield, high butanol proportion, easy-handling and time-saving system. These results demonstrated the potential advantage of symbiosis. This study also provides a promising strategy for butanol fermentation. PMID- 26272092 TI - Biotechnological applications of extremophiles, extremozymes and extremolytes. AB - In the last decade, attention to extreme environments has increased because of interests to isolate previously unknown extremophilic microorganisms in pure culture and to profile their metabolites. Microorganisms that live in extreme environments produce extremozymes and extremolytes that have the potential to be valuable resources for the development of a bio-based economy through their application to white, red, and grey biotechnologies. Here, we provide an overview of extremophile ecology, and we review the most recent applications of microbial extremophiles and the extremozymes and extremolytes they produce to biotechnology. PMID- 26272093 TI - Towards an effective biosensor for monitoring AD leachate: a knockout E. coli mutant that cannot catabolise lactate. AB - Development of a biosensor for the convenient measurement of acetate and propionate concentrations in a two-phase anaerobic digestor (AD) requires a bacterium that will be unresponsive to the other organic acids present in the leachate, of which lactate is the most abundant. Successive gene knockouts of E.coli W3110 D-lactate dehydrogenase (dld), L-lactate dehydrogenase (lldD), glycolate oxidase (glcD) and a suspected L-lactate dehdrogenase (ykgF) were performed. The resulting quadruple mutant (IMD Wldgy) was incapable of growth on D- and L-lactate, whereas the wild type grew readily on these substrates. Furthermore, the O2 consumption rates of acetate-grown IMD Wldgy cell suspensions supplied with either acetate (0.1 mM) or a synthetic leachate including acetate (0.1 mM) and DL-lactate (1 mM) were identical (2.79 and 2.70 mg l(-1) min(-1), respectively). This was in marked contrast to similar experiments with the wild type which gave initial O2 consumption rates of 2.00, 2.36 and 2.97 mg l(-1) min( 1) when cell suspensions were supplied with acetate (0.1 mM), acetate (0.1 mM) plus D-lactate (1 mM) or acetate (0.1 mM) plus L-lactate (1 mM), respectively. The knockout strain provides a platform for the design of a biosensor that can accessibly monitor acetate and propionate concentrations in AD leachate via O2 uptake measurements. PMID- 26272094 TI - Expression and properties of three novel fungal lipases/sterol esterases predicted in silico: comparison with other enzymes of the Candida rugosa-like family. AB - Lipases from the Candida rugosa-like family are enzymes with great biotechnological interest. In a previous work, several enzymes from this family were identified by in silico mining of fungal genomes. Here, we describe the cloning, expression, and characterization of putative lipases from the genomes of Nectria haematococca, Trichoderma reesei, and Aspergillus niger and compared their catalytic properties with those of OPE, a well-characterized sterol esterase/lipase from Ophiostoma piceae. All of them hydrolyzed p-nitrophenol esters and triglycerides with different efficiency, but their activity against sterol esters was dissimilar, and the enzyme from A. niger was unable of hydrolyzing these substrates while OPE showed the best k cat values, which in general leads to an improved catalytic efficiency. Similarly, OPE was the best catalyst in the synthesis of beta-sitostanyl oleate, followed by the commercial CRL from C. rugosa, while the A. niger enzyme was unable to produce this compound. When the enzymes were evaluated for caprolactone oligomerization, the A. niger enzyme gave similar results than CRL, being OPE slightly more efficient. The expression of the putative selected proteins allowed their functional validation, suggesting that the hydrophobicity of the lid region may be an important factor, although the enzymatic efficiency is also influenced by other parameters, as the aggregation state and the size and morphology of the tunnel, where substrate recognition and catalysis takes place. PMID- 26272095 TI - DasR is a pleiotropic regulator required for antibiotic production, pigment biosynthesis, and morphological development in Saccharopolyspora erythraea. AB - The GntR-family transcription regulator, DasR, was previously identified as pleiotropic, controlling the primary amino sugar N-acetylglucosamine (GlcNAc) and chitin metabolism in Saccharopolyspora erythraea and Streptomyces coelicolor. Due to the remarkable regulatory impact of DasR on antibiotic production and development in the model strain of S. coelicolor, we here identified and characterized the role of DasR to secondary metabolite production and morphological development in industrial erythromycin-producing S. erythraea. The physiological studies have shown that a constructed deletion of dasR in S. erythraea resulted in antibiotic, pigment, and aerial hyphae production deficit in a nutrient-rich condition. DNA microarray assay, combined with quantitative real-time reverse transcription PCR (qRT-PCR), confirmed these results by showing the downregulation of the genes relating to secondary metabolite production in the dasR null mutant. Notably, electrophoretic mobility shift assays (EMSA) showed DasR as being the first identified regulator that directly regulates the pigment biosynthesis rpp gene cluster. In addition, further studies indicated that GlcNAc, the major nutrient signal of DasR-responsed regulation, blocked secondary metabolite production and morphological development. The effects of GlcNAc were shown to be caused by DasR mediation. These findings demonstrated that DasR is an important pleiotropic regulator for both secondary metabolism and morphological development in S. erythraea, providing new insights for the genetic engineering of S. erythraea with increased erythromycin production. PMID- 26272096 TI - The biostimulation of anaerobic digestion with (semi)conductive ferric oxides: their potential for enhanced biomethanation. AB - The effect of biostimulation with ferric oxides, semiconductive ferric oxyhydroxide, and conductive magnetite on the anaerobic digestion of dairy wastewater was examined in a batch mode. The reactors supplemented with ferric oxyhydroxide (R2) and magnetite (R3) showed significantly enhanced biomethanation performance compared with the control (R1). The removal of chemical oxygen demand (COD) after 30 days was 31.9, 59.3, and 82.5% in R1, R2, and R3, respectively. The consumed COD was almost fully recovered as biogas in R2 and R3, while only 79% was recovered in R1. The total energy production as biogas was accordingly 32.2, 71.0, and 97.7 kJ in R1, R2, and R3, respectively. The reactors also differed in the acid formation profile with more propionate and butyrate found in R1 and more acetate found in R3. The enhanced biomethanation seems to be associated with variations in the bacterial community structure supposedly induced by the ferric oxides added. In contrast, no evident variation was observed in the archaeal community structure among the reactors. The potential electric syntrophy formed between Methanosaeta concilii-like methanogens and electroactive iron-reducing bacteria, particularly Trichococcus, was likely responsible for the enhanced performance. The stimulated growth of fermentative iron reducers may also have contributed by altering the metabolic characteristics of the bacterial communities to produce more favorable acidogenic products for methanogenesis. The overall results suggest the potential of biostimulation with (semi)conductive ferric oxides to enhance the rate and efficiency of the biomethanation of organic wastes. This seems to be potentially attractive, as increasing attention is being paid to the energy self-sufficiency of waste/wastewater treatment processes today. PMID- 26272097 TI - Biosynthesis and function of bacterial dialkylresorcinol compounds. AB - This review summarizes the research of bacterially produced dialkylresorcinols (DARs). We will give an overview about the DAR-related research during the last 40 years. Furthermore, a brief introduction into the class of ketosynthases (KS) and examples of these enzymes which show a deviation to the usual catalytic activity is given. One of these is DarB, which is involved in the DAR biosynthesis. The clustering and distribution of the DAR biosynthesis gene clusters (BGC), that has been identified in more than 100 genomes from taxonomically distinct bacteria, is discussed regarding the structures of the biosynthetic products from these BGCs. Finally, the biological activities of described DARs are summarized and possible methods for the detection and structure elucidation of DARs are given. PMID- 26272099 TI - Factors affecting the interactions between beta-lactoglobulin and fatty acids as revealed in molecular dynamics simulations. AB - Beta-lactoglobulin (BLG), a bovine dairy protein, is a promiscuously interacting protein that can bind multiple hydrophobic ligands. Fatty acids (FAs), common hydrophobic molecules bound to BLG, are important sources of fuel for life because they yield large quantities of ATP when metabolized. The binding affinity increases with the length of the ligands, indicating the importance of the van der Waals (vdW) interactions between the hydrocarbon tail and the hydrophobic calyx of BLG. An exception to this rule is caprylic acid (OCA) which is two carbon shorter but has a stronger binding affinity than capric acid. Theoretical calculations in the current literature are not accurate enough to shed light on the underlying physics of this exception. The computed affinity values are greater for longer fatty acids without respect for the caprylic exception and those values are generally several orders of magnitude away from the experimental data. In this work, we used hybrid steered molecular dynamics to accurately compute the binding free energies between BLG and the five saturated FAs of 8 to 16 carbon atoms. The computed binding free energies agree well with experimental data not only in rank but also in absolute values. We gained insights into the exceptional behavior of caprylic acid in the computed values of entropy and electrostatic interactions. We found that the electrostatic interaction between the carboxyl group of caprylic acid and the two amino groups of K60/69 in BLG is much stronger than the vdW force between the OCA's hydrophobic tail and the BLG calyx. This pulls OCA to the top of the beta barrel where it is easier to fluctuate, giving rise to greater entropy of OCA at the binding site. PMID- 26272098 TI - Experience of the Spiritist Hospital Chaplaincy Service: A Retrospective Study. AB - The Hospital Chaplaincy service is made of religious volunteer work done by representatives of various religions properly trained to offer spiritual support to hospitalized patients, as well as their families, contributing as a source of protection, comfort and restoring faith in the face of illness. The objective of this study is to present a retrospective analysis of records made by chaplains, guided by the Spiritist Medical Association of Piracicaba, through 7419 calls to 2191 patients admitted at Unimed Hospital of Piracicaba in 2014. The results contributed to the production of scientific documentation about this new holistic model that still lies in acceptance phase in the country. PMID- 26272101 TI - Sources of organisational resiliency during the Thailand floods of 2011: a test of the bonding and bridging hypotheses. AB - Based on the Institutional Collective Action framework, this research tests the impact of two competing hypotheses--bonding and bridging--on enhancing organisational resiliency. The bonding hypothesis posits that organisational resiliency can be achieved if an organisation works closely with others, whereas the bridging hypothesis argues that such a structure places considerable stress on an organisation and advocates for an organisation to position itself as a central actor to gain access to novel resources from a diverse set of entities to achieve resiliency. The paper analyses data gathered from semi-structured interviews with 44 public, private, and non-profit organisations serving communities affected by the Great Floods of 2011 in the Thai capital, Bangkok (urban), and in Pathum Thani (suburban) and Ayutthaya (rural) provinces. The findings suggest that: organisational resiliency was associated with the bridging effect; organisations in the rural province were more resilient than those in the suburban and urban centres; and private and non-governmental organisations generally were more resilient than public sector organisations. The findings highlight the importance of fostering multi-sector partnerships to enhance organisational resiliency for disaster response. PMID- 26272100 TI - What are patients' expectations about the organization of their primary care physicians' practices? AB - BACKGROUND: To our knowledge no study has at the same time assessed patients' satisfaction and their expectations concerning the organizational and contextual aspects of health care provided by their primary care physician (PCP). Assessing these aspects is important to inform future primary healthcare service planning. Our objective was thus to document patients' satisfaction with and expectations from their PCP, in terms of availability and organization of their practices, and to assess whether these indicators varied across age groups and type of practice (solo, duo, group). METHODS: Cross-sectional study based on the answers to questionnaires completed by patients consulting their PCP in Geneva, Switzerland. A random sample of PCPs was asked to recruit consecutively between 50 and 100 patients coming to the practice for a scheduled medical consultation. The patients were asked to complete an anonymous questionnaire centered on their satisfaction levels and expectations towards their PCP. RESULTS: One thousand six hundred thirty-seven patients agreed to participate (participation rate: 97%, women: 63%, mean age: 54 years). Patient satisfaction was high for all the items, except for the availability of the doctor by phone and for the waiting time in the waiting room. The satisfaction rate increased with age and was higher for small practices. In relation to patients' expectations from their doctor, older patients and patients visiting larger practices tended to be more demanding. CONCLUSIONS: Patients are generally highly satisfied with their PCP. They have a wide range of expectations which should be taken into account when considering potential improvements. PMID- 26272103 TI - Abnormal megakaryopoiesis and platelet function in cyclooxygenase-2-deficient mice. AB - Previous studies suggest that cyclooxygenase-2 (COX-2) might influence megakaryocyte (MK) maturation and platelet production in vitro. Using a gene deletion model, we analysed the effect of COX-2 deficiency on megakaryopoiesis and platelet function. COX-2-/- mice (10-12 weeks old) have hyper-responsive platelets as suggested by their enhanced aggregation, TXA2 biosynthesis, CD62P and CD41/CD61 expression, platelet-fibrinogen binding, and increased thromboembolic death after collagen/epinephrine injection compared to wild-type (WT). Moreover, increased platelet COX-1 expression and reticulated platelet fraction were observed in COX-2-/- mice while platelet count was similar to WT. MKs were significantly reduced in COX-2-/- bone marrows (BMs), with high nuclear/cytoplasmic ratios, low ploidy and poor expression of lineage markers of maturation (CD42d, CD49b). However, MKs were significantly increased in COX-2-/- spleens, with features of MK maturation markers which were not observed in MKs of WT spleens. Interestingly, the expression of COX-1, prostacyclin and PGE2 synthases and prostanoid pattern were modified in BMs and spleens of COX-2-/- mice. Moreover, COX-2 ablation reduced the percentage of CD49b+ cells, the platelet formation and the haematopoietic stem cells in bone marrow and increased their accumulation in the spleen. Splenectomy decreased peripheral platelet number, reverted their hyper-responsive phenotype and protected COX-2-/- mice from thromboembolism. Interestingly, fibrosis was observed in spleens of old COX 2-/- mice (28 weeks old). In conclusion, COX-2 deletion delays BM megakaryopoiesis promoting a compensatory splenic MK hyperplasia, with a release of hyper-responsive platelets and increased thrombogenicity in vivo. COX-2 seems to contribute to physiological MK maturation and pro-platelet formation. PMID- 26272104 TI - Paravertebral nerve block catheters using chloroprocaine in infants with prolonged mechanical ventilation for treatment of long-gap esophageal atresia. AB - BACKGROUND: Infants with long-gap esophageal atresia (LGEA) undergo repeated thoracotomies for staged surgical repair known as the Foker process (FP). Associated prolonged mechanical ventilation results in exposure to high doses of opioids and benzodiazepines, and prolonged weaning times and ICU stays. AIM: The aim of this study was to determine the effectiveness of short-term paravertebral nerve block (PVNB) catheters in reducing opioid/benzodiazepine exposure and effects on clinical variables. METHODS: The medical records of seventeen infants were retrospectively reviewed; 11 with PVNB and six without (CG). PVNB were placed using ultrasound-guidance and chloroprocaine infusions implemented in the ICU. Opioids and benzodiazepines were administered via the protocol for 5 days following thoracotomies for Foker-I and Foker-II. RESULTS: Foker-I: Average reduction in morphine and midazolam consumption was 36% (2.18 vs 3.40 mg.kg(-1) .day(-1) ; P < 0.001) and 31% (2.25 vs 3.25 mg.kg(-1) .day(-1) ; P = 0.033), respectively, in the PVNB compared with CG. Foker-II: Average reduction in morphine and midazolam consumption was 39% (3.19 vs 5.27 mg.kg(-1) .day(-1) ) and 38% (3.46 mg.kg(-1) .day(-1) vs 5.62; P < 0.001), respectively in the PVNB compared with CG. 24-h prior to extubation: Average reduction in morphine and midazolam consumption was 50% (2.91 vs 5.85 mg.kg(-1) .24 h(-1) ; p = 0.023) and 61% (2.27 vs 5.83 mg.kg(-1) .24 h(-1) ; P = 0.004), respectively, in the PVNB compared with CG. Infusion wean time, (independence from opioid/midazolam infusions) following extubation was 5 days in the PVNB group and 15 days in CG (P = 0.005). Median ICU stay (IQR) was 40 days (34-45 days) in PVNB patients and 71 days (42-106 days) in controls (P = 0.02). PVNB catheters were left an average of 7 days and there were no complications associated with the nerve blocks. CONCLUSION: Short-term PVNB placement decreases opioid and benzodiazepine exposure, weaning days and ICU stay in infants undergoing prolonged mechanical ventilation for LGEA repair in this small pilot study. Larger studies are warranted to confirm results. PMID- 26272107 TI - Chip calorimetry for the sensitive identification of hexogen and pentrite from their decomposition inside copper oxide nanoparticles. AB - Smart detection systems for explosive sensors are designed both to detect explosives in the air at trace level and identify the threat for a specific response. Following this need we have succeeded in using microthermal analysis to sensitively identify and discriminate between RDX and PETN explosive vapors at trace level. Once the explosive vapor is trapped in a porous material, heating the material at a fast rate of 3000 K/s up to 350 degrees C will result in a thermal pattern specifically corresponding to the explosive and its interaction with the porous material. The explosive signatures obtained make it possible to simultaneously identify the presence and the nature of the explosive vapor in just a few milliseconds. Therefore, this also allows the development of multitarget devices using porous material for capturing the vapor combined with microthermal analysis for fast detection and identification. So far it is the first time that chip calorimetry has been used to characterize and identify explosives in vapor state. PMID- 26272105 TI - Deregulation of microRNA expression in peripheral blood mononuclear cells from patients with HCV-related malignancies. AB - BACKGROUND AND AIM: Hepatocellular carcinoma is one of the major causes of death due to cancer worldwide, and its association with hepatitis C virus infection has been definitively established. Hepatitis C virus is also involved in the pathogenesis of non-Hodgkin's lymphoma. This is the only virus infecting humans that is able to induce two different malignancies. We analyzed the expression levels of a panel of microRNA in peripheral blood mononuclear cells of patients with hepatitis C virus-related malignancies in order to find a disease-associated deregulation and identify specific biomarkers. METHODS: We tested peripheral blood mononuclear cells isolated from patients with hepatocellular carcinoma, non Hodgkin's lymphoma, hepatitis C virus without malignancies and healthy subjects for a panel of microRNA selected on the basis of previous studies. MicroRNA expression was evaluated by real-time PCR. RESULTS: Our results showed an upregulation of miRNA-21 and downregulation of miRNA-26b in hepatocellular carcinoma and non-Hodgkin's lymphoma patients compared to controls (p < 0.001). Deregulation of miRNA-16 and miRNA-155 was limited to lymphoma patients. CONCLUSIONS: This study shows that some microRNAs are differently expressed in peripheral blood mononuclear cells from hepatitis C virus patients who develop hepatocellular carcinoma or lymphoma, while others share a common behavior. Thus, analysis of the expression of microRNAs could be a noninvasive marker of hepatitis C virus-related carcinogenesis. This analysis could be a suitable tool for identifying the existence of a malignancy and also discriminating between these two hepatitis C virus-related cancers. PMID- 26272106 TI - Admissions for hepatitis B reactivation in patients receiving immunosuppressive therapy remain unchanged from 1999 to 2014. AB - BACKGROUND: Reactivation of hepatitis B virus (HBV) replication in patients with chronic or past HBV infection receiving immunosuppressive therapy (IST) can be prevented through HBV screening and prophylactic antiviral therapy. We aimed to determine the occurrence of severe HBV reactivation secondary to IST in the era of HBV nucleos/tide analogs, the implicated IST, and outcomes. METHODS: We conducted a retrospective chart review of adult patients who were HBsAg+ and HBV DNA+ and had received IST within 90 days of admission to our hospital. RESULTS: Of 1446 patients with HBV diagnosis code admitted from 1999 to 2014, 17 had HBV reactivation, 8 of whom were admitted after 2009. Nine patients had hematologic conditions, three solid organ transplants, one hepatocellular carcinoma, and four other nonmalignant diseases. Implicated IST included chemotherapy, prednisone, antirejection therapies, budesonide, and a JAK-2 inhibitor. Three patients were screened for HBV prior to IST, but none was given antiviral prophylaxis. Six patients were initially admitted to other facilities, only two were tested for HBV, and one was started on antiviral therapy prior to transfer. At admission to our hospital, all 17 were HBsAg+ and HBV DNA+. Despite antiviral therapy, five patients decompensated, three died, and two had a liver transplant. CONCLUSION: Severe HBV reactivation requiring hospital admission continues to occur because HBV screening was not performed and a prophylactic antiviral not given to those who tested positive. HBV reactivation can occur in a variety of clinical settings and in association with drugs not considered to be highly immunosuppressive. PMID- 26272109 TI - Idiopathic Carpal Tunnel Syndrome: Evaluation of the Depth of the Carpal Tunnel by Ultrasonography. AB - The objective of the work described here was to evaluate the depth of the carpal tunnel (DCT) in patients with idiopathic carpal tunnel syndrome (CTS) and healthy volunteers by ultrasonography (US), through measurement of the distance from the flexor retinaculum to the surface of the capitate bone at the carpal tunnel outlet, and compare it with other ultrasonographic and electrophysiologic parameters in CTS. The study was conducted in 60 non-diabetic patients with idiopathic carpal tunnel syndrome (unilateral n = 37, bilateral n = 23) evidenced by electrophysiologic diagnosis according to the criteria of the American Association of Electrodiagnostic Medicine (AAEM). Furthermore, 40 hands from 20 healthy volunteers were examined. Median nerve cross-sectional area (CSA); flattening ratio (FR), the ratio of the length to the width of the median nerve; and DCT at the canal outlet were measured for all participants. The mean age was 35.6 +/- 9.48 y. The female-to-male ratio was 47:13 in the CTS patients. The sensitivity and specificity were 82% and 95% for CSA, 75% and 60% for FR and 75% and 87.5% for DCT, respectively. Differences between patients and healthy controls were significant for all three parameters, greatest for DCT, followed by CSA and then FR. We conclude that DCT increased in CTS and this new parameter is comparable in sensitivity and specificity to CSA and FR. DCT increased independently of the cause of the CTS (decrease in size of canal or increase in contents). PMID- 26272108 TI - Respiration artifact correction in three-dimensional proton resonance frequency MR thermometry using phase navigators. AB - PURPOSE: To develop reliable three-dimensional (3D) segmented echo planar imaging (seg-EPI) proton resonance frequency (PRF) temperature monitoring in the presence of respiration-induced B0 variation. METHODS: A free induction decay (FID) phase navigator was inserted into a 3D seg-EPI sequence before and after EPI readout to monitor B0 field variations. Using the field change estimates, the phase of each k-space line was adjusted to remove the additional phase from the respiratory induced off-resonance. This correction technique was evaluated while heating with MR-guided focused ultrasound (MRgFUS) in phantoms with simulated breathing and during nonheating conditions in healthy in vivo breasts. RESULTS: With k-space phase correction, the standard deviation of magnitude images and PRF temperature measurements in breast from five volunteers improved by an average factor of 1.5 and 2.1, respectively. Improved accuracy of temperature estimates was observed after correction while heating with MRgFUS in phantoms. CONCLUSION: Phase correction based on two FID navigators placed before and after the echo train provides promising results for implementing 3D monitoring of thermal therapy treatments in the presence of field variations due to respiration. Magn Reson Med 76:206-213, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26272112 TI - Methodology for solid state NMR off-resonance study of molecular dynamics in heteronuclear systems. AB - Methodology for the study of dynamics in heteronuclear systems in the laboratory frame was described in the previous paper [1]. Now the methodology for the study of molecular dynamics in the solid state heteronuclear systems in the rotating frame is presented. The solid state NMR off-resonance experiments were carried out on a homemade pulse spectrometer operating at the frequency of 30.2 MHz for protons. This spectrometer includes a specially designed probe which contains two independently tuned and electrically isolated coils installed in the coaxial position on the dewar. A unique probe design allows working at three slightly differing frequencies off and on resonance for protons and at the frequency of 28.411 MHz for fluorine nuclei with complete absence of their electrical interference. The probe allows simultaneously creating rf magnetic fields at off resonance frequencies within the range of 30.2-30.6 MHz and at the frequency of 28.411 MHz. Presented heteronuclear cross-relaxation off-resonance experiments in the rotating frame provide information about molecular dynamics. PMID- 26272110 TI - Regulation of alpha4beta2alpha5 nicotinic acetylcholinergic receptors in rat cerebral cortex in early and late adolescence: Sex differences in response to chronic nicotine. AB - Chronic nicotine administration in animals, and smoking in humans, causes up regulation of alpha4beta2* neuronal nicotinic receptors (nAChRs), which has been hypothesized to contribute to the addictive actions of nicotine. We used a rat model to test whether such up-regulatory effects differ in adolescents versus adults, and in males versus females. Following chronic treatment with nicotine or saline via subcutaneous osmotic minipumps, we measured alpha4beta2 and alpha4beta2alpha5 nAChRs in cerebral cortex using [3H]epibatidine to label assembled nAChRs, and selective antibodies to measure the individual subunits via immunoprecipitation. For the first time, we provide a detailed characterization of the response of both alpha4beta2 and alpha4beta2alpha5 nAChRs in female adolescent rat cerebral cortex. We found differences in nicotine-induced up regulation between males and females in early adolescence that are absent in both late adolescence and adulthood. Males showed significant up-regulation at PN28 which was absent in age-matched females. These results demonstrate sex differences in the susceptibility of alpha4beta2* nAChRs to the effects of chronic nicotine exposure in the cerebral cortex based on age. PMID- 26272111 TI - Association of Hepatitis C Virus Infection with Proteinuria and Glomerular Filtration Rate. AB - AIM: Despite several studies, the extent to which hepatitis C virus (HCV) infection is associated with chronic kidney disease (CKD) remains controversial. Thus, we examined the relationship between HCV and CKD using the continuous National Health and Nutrition Examination Survey (1999-2012). METHODS: Specimens positive for anti-HCV antibodies were retested and confirmed with recombinant immunoblot assay (RIBA). Proteinuria was defined as urine albumin creatinine ratio > 30 mg/g. CKD was defined as estimated glomerular filtration rate (GFR) < 60 mL/min/1.73 m(2) . We used linear and logistic regression models to examine the association between HCV and outcomes with and without adjustment for age, sex, race, hypertension, diabetes mellitus, and body mass index and accounting for the complex survey design. RESULTS: Of the 33,729 eligible participants, HCV infection was present in 659 (1.73%). In unadjusted and adjusted analyses, HCV was associated with proteinuria (OR = 1.40, p = 0.01 and OR = 1.50, p = 0.02, respectively). In both unadjusted and adjusted analyses, individuals with HCV had significantly higher GFR than individuals without (1.4 mL/min, p = 0.04 and 2.7 mL/min, p < 0.001, respectively). We did not find an association of HCV with CKD in adjusted or unadjusted analyses. CONCLUSION: HCV infection is associated with proteinuria and high GFR but not with CKD. The biological mechanism of the observed association needs further study. PMID- 26272114 TI - Towards a dimensional model of depression: Evidence from Chinese samples. PMID- 26272113 TI - Changes in aquaporin 5 in the non-ciliated cells of mouse oviduct according to sexual maturation and oestrous cycle. AB - Aquaporin (AQP) water channels play an important role in fluid homeostasis and the control of epithelial cell volume. To understand the oviductal fluid homeostasis, the expression of aqp5 was examined in mouse oviduct. In the oviduct of cycling females, aqp1, aqp3, aqp4, aqp5, aqp6, aqp7, aqp8, and aqp11 mRNA were detected. Of these, expression of aqp5 mRNA increased significantly from the early prepubertal period to puberty. Epithelial AQP5 immunoreactivity was markedly increased during the same period and was most notable in the infundibulum. In immature female mice (3 weeks old), gonadotropin (pregnant mare's serum gonadotropin (5IU/head) and human chorionic gonadotropin (5IU/head), single intraperitoneal injection) significantly increased oviductal aqp5 mRNA and AQP5 immunoreactivity in oviduct epithelia. In adult mouse oviduct epithelia, AQP5 was primarily found in the apical membrane, subapical cytoplasm and basolateral membrane of secretory non-ciliated cells, whereas weak to negligible immunoreactivity was found in beta-tubulin-positive ciliated cells. Taking into account the fact that non-ciliated cells are well developed with subapical secretory vesicles as well as endosomes, AQP5 may also participate in the secretion and endocytosis in addition to water movement through non-ciliated secretory cells. AQP5 immunoreactivity was also found in the isthmic muscle and lamina propria beneath the epithelia. In cycling females, oviductal aqp5 mRNA levels were the highest at oestrus and the lowest at di-oestrus. AQP5 immunoreactivity in non-ciliated cells was notable in the infundibulum, where AQP5 immunoreactivity was relatively high at oestrus but low at dioestrus and pro oestrus, indicating synchrony between aqp5 gene activation and the ovarian cycle. Together, the findings of the present study indicate that aqp5 specific to non ciliated cells is activated during sexual maturation, supporting fluid homeostasis in mouse oviduct. PMID- 26272115 TI - The latent structure of depression among Chinese: A taxometric analysis in a nationwide urban sample. AB - The latent structure of psychopathology is one of the fundamental issues in psychopathology research and one which has caused considerable and prolonged debate. To determine the latent structure of depression in the Chinese population, taxometric procedures were used to evaluate the latent structure of depressive symptoms as assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Four indicators were included: (1) depressed mood, (2) positive affect, (3) somatic, and (4) interpersonal symptoms. Participants were 6,132 individuals from a general population-based nationwide urban sample. We applied three taxometric analyses: mean above minus below a cut, maximum eigenvalue, and latent mode as well as simulated comparison data analyses to depression data. Results of the analyses provided converging evidence for a dimensional solution. Hence, the latent structure of depressive symptoms measured using the CES-D exists on a continuum rather than as discrete categories. Future studies using thresholds for dichotomizing depression and comparing depressed and nondepressed groups formed on the basis of CES-D scores could be reconsidered. PMID- 26272117 TI - Etiological heterogeneity of symptom dimensions of adolescent depression. AB - The aim was to investigate the underlying factor structure of adolescent depression and etiological heterogeneity in the symptom dimensions of adolescent depression. The sample included 842 pairs of same-sex adolescent twins, among which 613 pairs were monozygotic twins and 229 pairs were dizygotic twins. The ages of the participants ranged from 11 to 17 years (M = 13.64, SD = 1.80). Adolescents' depressive symptoms were assessed using the self-reported Children's Depression Inventory. Exploratory and confirmatory factor analyses were used to explore the factor structure of youth depression and twin genetic analyses were employed to estimate genetic and environmental influences on the derived dimensions. Results showed that adolescent depression encompassed five correlated dimensions: dysphoria mood, somatic symptoms, study and externalizing problems, anhedonia symptoms, and cognitive symptoms. These five symptom dimensions had heterogeneous etiologies: Dysphoria mood, somatic symptoms, and cognitive symptoms were moderately heritable (heritability ranged from 33 to 40%), whereas study and externalizing problems, and anhedonia symptoms were mainly environmentally influenced with minimal genetic basis. Our findings supported the multidimensionality of adolescent depression and the etiological heterogeneity of these symptom dimensions. PMID- 26272116 TI - Aberrant functional connectivity of the hippocampus in older adults with subthreshold depression. AB - Major depression disorder (MDD) is closely associated with functional and structural changes in the hippocampus (HC). Neuroimaging studies have demonstrated abnormal functional connectivity (FC) of the HC in patients with MDD, but it remains unknown whether this abnormal hippocampal FC pattern occurs in individuals with subthreshold depression (StD) who are at high risk of MDD. Resting-state functional magnetic resonance imaging data were collected from 19 elderly individuals with StD and 18 normal controls. Whole brain voxel-wise FC analyses were conducted to investigate the hippocampal FC pattern by selecting the HC as the region of interest, and correlation analyses were performed to explore the association of altered FC of the HC with self-reported depressive symptoms. The results showed that elderly individuals with StD had substantially decreased FC of the HC to the prefrontal and cuneus cortices compared with healthy normal controls. Moreover, the strength of HC-cuneus connectivity was correlated with self-reported depressive symptoms in elderly individuals with StD. These findings suggest that dysfunctional integration within the HC and cortical regions may occur at an early stage of depression. PMID- 26272118 TI - The COMT gene variant is associated with depression's decreased positive affect symptoms in Chinese adults. AB - This study examined the association between the COMT Val(158) Met genotype and depression symptoms. A total of 326 Chinese adults who experienced the deadly 2008 Wenchuan earthquake and lost children during the disaster participated in this study. Depression symptoms were measured using the Center for Epidemiological Studies Depression Scale (CES-D). The single nucleotide polymorphism (SNP) was successfully genotyped using the MassARRAY system. Results indicated that although the Val(158) Met genotype was not associated with total depression symptoms, it was significantly correlated with decreased positive affect symptoms of depression in males. The findings indicated that COMT may play an important functional role in the development of depression, and contribute to the extant knowledge of the genetic basis and sex-specific expression of symptoms in depression. PMID- 26272119 TI - Low self-esteem as a vulnerability differentially predicts symptom dimensions of depression in university students in China: A 6-month longitudinal study. AB - This 6-month longitudinal study examined how self-esteem as a vulnerability differentially predicts symptom dimensions of depression in a sample of university students from Hunan Province, China. Baseline and 6-month follow-up data were obtained from 659 university students. During an initial assessment, participants completed measures assessing their low self-esteem, depressive symptoms, and the occurrence of daily hassle. Participants subsequently completed measures assessing daily hassle and depressive symptoms once per month for 6 months. Higher low self-esteem scores were associated with greater increases in the somatic complaints and positive affect dimensions, but not the depressed affect and interpersonal problem dimensions of depressive symptoms following daily hassle in Chinese university students. The results of the current study suggest that low self-esteem plays a significant role in the etiology and course of depressive symptoms that develop in response to exposure to daily hassles. Consistent with the vulnerability-stress model of depression, the results suggest that low self-esteem serves as a risk factor and daily hassles serve as a precipitating factor. PMID- 26272122 TI - (99m)Tc-MDP bone scintigraphy of three brothers affected by Multiple Osteochondromas. PMID- 26272121 TI - Use of positron emission tomography (PET) for the diagnosis of large-vessel vasculitis. AB - The term vasculitis encompasses a heterogeneous group of diseases that share the presence of inflammatory infiltrates in the vascular wall. The diagnosis of large vessel vasculitis is often a challenge because the presenting clinical features are nonspecific in many cases and they are often shared by different types of autoimmune and inflammatory diseases including other systemic vasculitides. Moreover, the pathogenesis of large-vessel vasculitis is not fully understood. Nevertheless, the advent of new imaging techniques has constituted a major breakthrough to establish an early diagnosis and a promising tool to monitor the follow-up of patients with largevessel vasculitis. This is the case of the molecular imaging with the combination of positron emission tomography with computed tomography (PET/CT) using different radiotracers, especially the (18)F fluordeoxyglucose ((18)F-FDG). In this review we have focused on the contribution of (18)F-FDG PET in the diagnosis of large-vessel vasculitis. PMID- 26272123 TI - Saffron: a natural product with potential pharmaceutical applications. AB - OBJECTIVES: Recently, a great deal of interest has been developed to isolate and investigate novel bioactive components from natural resources with health beneficial effects. Saffron is the dried stigma of Crocus sativus L. and has been used for centuries in traditional medicine mainly for its healing properties, as well as for the treatment of various pathological conditions. Objectives of the present review are to unravel its therapeutic properties and investigate the potential applications of saffron in contemporary therapy of a wide spectrum of diseases and summarize previous and current evidence regarding the biological/pharmacological activities of saffron and its active ingredients and their possible therapeutic uses. KEY FINDINGS: Recent phytochemistry and pharmacological experiments have indicated that crocin and safranal, the major active ingredients of saffron, exert important actions, such as antioxidant, anti tumor, anti-diabetic, anti-inflammatory and anti-atherosclerotic. Unfortunately, the vast majority of those data derive from in vitro studies, whereas a limited number of in vivo experiments support the aforementioned effects. In addition to studies with mechanistic implications, very few clinical trials provide preliminary evidence of saffron potentiality to alleviate depression and increase cognitive function in patients with Alzheimer's disease. SUMMARY: The history and structural features of saffron constituents are given in the first part of the review, followed by a comprehensive and critical presentation of the published preclinical and clinical studies and review papers on the pharmacology and possible therapeutic uses of saffron and its main active components crocin and safranal. PMID- 26272125 TI - Optimal design for studying mucoadhesive polymers interaction with gastric mucin using a quartz crystal microbalance with dissipation (QCM-D): Comparison of two different mucin origins. AB - The objective of this present study was to develop an efficient and simple method, based on the use of a quartz crystal microbalance with dissipation (QCM D), to evaluate the mucoadhesive characteristics of cationic polymers; chitosan, thiolated chitosan (chitosan-SH), and polyallylamine hydrochloride (PAH), and anionic polymers; hyaluronic acid (HA) and thiolated hyaluronic acid (HA-SH). The experiments were carried out at pH 4 to assess the interaction between mucoadhesive polymers and a mucin-coated gold surface. A key point in the QCM-D protocol development was to evaluate two sources of mucin: native porcine gastric mucin (NPGM) and commercially available porcine gastric mucin (CPGM). QCM-D has shown its potential as a highly sensitive technique that provides information about the interaction of mucoadhesive polymers with gastric mucin. The technique would allow the classification of these polymers in order to further assess their application as base materials for nanocarriers, designed to interact with the mucosal barrier which represents a stumbling block for drug adsorption. PMID- 26272126 TI - Common and rare variants associated with kidney stones and biochemical traits. AB - Kidney stone disease is a complex disorder with a strong genetic component. We conducted a genome-wide association study of 28.3 million sequence variants detected through whole-genome sequencing of 2,636 Icelanders that were imputed into 5,419 kidney stone cases, including 2,172 cases with a history of recurrent kidney stones, and 279,870 controls. We identify sequence variants associating with kidney stones at ALPL (rs1256328[T], odds ratio (OR)=1.21, P=5.8 * 10(-10)) and a suggestive association at CASR (rs7627468[A], OR=1.16, P=2.0 * 10(-8)). Focusing our analysis on coding sequence variants in 63 genes with preferential kidney expression we identify two rare missense variants SLC34A1 p.Tyr489Cys (OR=2.38, P=2.8 * 10(-5)) and TRPV5 p.Leu530Arg (OR=3.62, P=4.1 * 10(-5)) associating with recurrent kidney stones. We also observe associations of the identified kidney stone variants with biochemical traits in a large population set, indicating potential biological mechanism. PMID- 26272128 TI - Bayesian restricted spatial regression for examining session features and patient outcomes in open-enrollment group therapy studies. AB - Group-based interventions have been developed for treating patients across a range of health conditions. Enrollment into such groups often occurs on an open (or rolling) basis. Conditional autoregression modeling of random session effects has been proposed to account for the expected correlation in session effects associated with the overlap in patient participation session to session. However, when the analytic objective is to examine the relationship between a fixed-effect session feature and a patient outcome using conditional autoregression, confounding might arise if the fixed session feature of interest and the random session effects vary across sessions in similar ways, resulting in bias and inflated standard errors of a fixed-effect session feature of interest. Motivated by the goal of examining the relationships between outcomes and the session features of leader and session module theme, we applied restricted spatial regression to the analysis of patient outcomes collected from 132 participants in an open-enrollment group for treating depression among patients of a residential alcohol and other drug treatment program, adapting the approach to the multilevel data structure of open-enrollment group data. As compared with standard conditional autoregression, the restricted regression approach resulted in more precise estimates of regression coefficients of the module theme and leader predictor variables. The restricted regression approach provides an important analytic tool for group therapy researchers who are investigating the relationship between key components of open-enrollment group therapy interventions and patient outcomes. PMID- 26272129 TI - Fluorescently-labeled RNA packaging into HIV-1 particles: Direct examination of infectivity across central nervous system cell types. AB - HIV penetrates the central nervous system (CNS), and although it is clear that microglia and to a lesser extent astrocytes are infected, whether certain other cell types such as neurons are infected remains unclear. Here, we confirmed the finding that RNAs of both cellular and viral origins are present in native HIV-1 particles and exploited this phenomenon to directly examine HIV-1 infectivity of CNS cell types. Using in vitro transcribed mRNAs that were labeled with a fluorescent dye, we showed that these fluorescent mRNAs were packaged into HIV-1 particles by directly examining infected cells using fluorescence microscopy. Cells in culture infected with these labeled virions showed the fluorescent signals of mRNA labels by a distinct pattern of punctate, focal signals within the cells which was used to demonstrate that the CXCR4-tropic NL4-3 strain was able to enter microglia and to a lesser extent astrocytes, but not neurons. The strategy used in the present study may represent a novel approach of simplicity, robustness and reliability for versatile applications in HIV studies, such as the determination of infectivity across a broad range of cell types and within sub populations of an individual cell type by direct visualization of viral entry into cells. PMID- 26272127 TI - Increased hepatic expression of miRNA-122 in patients infected with HCV genotype 3. AB - Hepatitis C virus (HCV) infection affects approximately 3 % of the world population. HCV targets hepatic tissue, and most infected patients develop a chronic infection. Currently, studies have demonstrated an association between HCV-RNA replication and miR-122, the most abundant microRNA in the liver. Our aim was to evaluate liver and serum expression of miR-122 in patients infected with HCV genotypes 1 and 3, and to identify possible associations between miR-122 expression and lipid profiles, HCV viral load, apolipoproteins and liver enzymes. MicroRNAs were isolated from blood and liver tissue, and miR-122 expression was quantified by real-time PCR. HCV viral load was quantified by real-time PCR and HCV genotype, and serum biomarkers were obtained from medical report. The levels of miR-122 were higher in liver than those in blood from individuals infected with HCV genotypes 1 and 3 (p < 0.0001). The tissue levels of miR-122 were higher in subjects infected with HCV genotype 3 (6.22-fold, p < 0.001). A positive correlation was observed between the blood and hepatic levels of miR-122 in patients infected with HCV genotype 1 (r = 0.302, p = 0.026); in these patients, an inverse correlation was observed between serum apolipoprotein A-II (ApoA-II) levels and the blood (r = -0.330; p = 0.014) and hepatic (r = -0.311; p = 0.020) levels of miR-122. In patients infected with HCV genotype 3, there was a positive correlation between the hepatic miR-122 and the high-density lipoprotein-HDL (r = 0.412, p = 0.036) and insulin (r = 0.478, p = 0.044). Lipid metabolism proteins and miR-122 expression levels have different relations in HCV-3- and HCV-1 infected patients. PMID- 26272130 TI - Systemic review of the prevention of pit and fissure caries of permanent molars by resin sealants in children in China. AB - AIM: The aim of the present study was to evaluate the relationship between pit and fissure sealants and the prevention of dental caries in permanent molars of children in China. METHODS: The Cochrane Handbook for Systematic Reviews of Interventions was followed. Articles published in English and Chinese from 2002 to 2013 were selected. All these studies were randomized clinical trials related to pit and fissure sealants on caries prevention. Data were analyzed using Software Review Manager 5.1. RESULTS: A search of the four largest Chinese medical literature databases and the PubMed/Medline database yielded a total of 397 clinical research studies about the effects of pit and fissure sealants on the prevention of dental caries; 20 original research studies were selected. In this meta-analysis, a total of 12 187 participants were included. Statistical analyses demonstrated a significant association between pit and fissure sealants and dental caries prevention for a 6-month follow-up period (combined odds ratio = 0.06, 95% CI: 0.01, 0.32, P < 0.0001). For other follow ups, there was a trend in pit and fissure sealants preventing the occurrence of dental caries. CONCLUSION: Current clinical evidence suggests that pit and fissure sealants are effective for dental caries prevention. Sealants should be placed as part of an overall caries prevention approach. Further research with larger sample sizes and rigorously-designed clinical trials are required to corroborate the current results. PMID- 26272131 TI - Isolation and Culture of Mouse Hepatocytes: Gender-Specific Gene Expression Responses to Chemical Treatments. AB - In this chapter, the isolation of primary mouse hepatocytes and their response to chemical treatment are described. We show that it is important to consider, in the experimental design, the sex of the animals to be used. We demonstrate this by measuring the effect of sex hormones or xenobiotics on the expression of flavin-containing monooxygenase 5 in cultures of primary hepatocytes isolated from male and female mice. PMID- 26272132 TI - Cryopreservation of Hepatocytes. AB - The use of cryopreserved hepatocytes has increased in the last decade due to the improvement of the freezing and thawing methods, and has even achieved acceptance by the US Food and Drug Administration for use in drug metabolizing enzyme induction studies. This chapter provides an overview of the theories behind the process of cryopreservation as well as practical advice on methods to cryopreserve hepatocytes, which retain functions similar to fresh cells after thawing. Parameters, such as cell density, cryoprotectants, freezing media, storage conditions, and thawing techniques, should be critically considered. Special emphasis is put on human hepatocytes, but information for the cryopreservation of animal hepatocytes is also described. PMID- 26272133 TI - Culture Conditions Promoting Hepatocyte Proliferation and Cell Cycle Synchronization. AB - The liver overcomes damages induced by harmful substances or viral infections and allows the use of extended resection in human therapy through its remarkable ability to regenerate. The regeneration process relies on the massive proliferation of differentiated hepatocytes that exit quiescence and undergo a limited number of cell cycles to restore the hepatic mass. Many discoveries on the regulation of hepatocyte proliferation have benefited from the use of in vitro models of cultures of primary hepatocytes as well as hepatoma cells as opposed to data obtained from in vivo models of liver regeneration, such as following partial hepatectomy in rodents. In this chapter, the most pertinent in vitro models used to promote the proliferation of hepatocytes and technical procedures to synchronize their progression throughout the cell cycle are presented with the goal to investigate the regulation of the hepatocyte cell cycle and the molecular pathways regulating liver regeneration. PMID- 26272135 TI - Culture and Functional Characterization of Human Hepatoma HepG2 Cells. AB - Hepatoma cell lines are frequently used as in vitro alternatives to primary human hepatocytes. Cell lines are characterized by their unlimited life span, stable phenotype, high availability, and easy handling. However, their major limitation is the lower expression of some metabolic activities compared with hepatocytes. HepG2 is a human hepatoma that is most commonly used in drug metabolism and hepatotoxicity studies. HepG2 cells are nontumorigenic cells with high proliferation rates and an epithelial-like morphology that perform many differentiated hepatic functions. In this chapter, freezing, thawing, and subculturing procedures for HepG2 cells are described. We further provide protocols for evaluating lipid accumulation, glycogen storage, urea synthesis, and phase I and phase II drug metabolizing activities in HepG2 cells. PMID- 26272137 TI - Serum-Free Directed Differentiation of Human Embryonic Stem Cells to Hepatocytes. AB - The increase in human liver disease worldwide is a major concern. At present, the only successful mode of treatment for failing liver function is organ transplantation. While highly successful, donor organs are a limited resource that cannot meet current demands. Therefore, alternative liver support strategies have been explored, including the use of the major and metabolic cell within the liver, the hepatocyte. While current approaches using human hepatocytes are very promising, donor material is still required and therefore suffers from similar limitations to whole organ transplantation. One alternative source of human hepatocytes being actively pursued in the field is pluripotent stem cells. Pluripotent stem cells are a scalable and renewable cell-based resource, which can be efficiently differentiated towards hepatocytes, including pluripotent stem cell lines that have been derived under good manufacturing practice conditions. Therefore, it is believed that this approach provides a promising model system for cell scale-up and differentiation. In the future, pluripotent stem cell derived hepatocytes could be used in the clinic to support failing liver function if they should be deemed fit for purpose. PMID- 26272138 TI - Human Skin-Derived Precursor Cells: Isolation, Expansion, and Hepatic Differentiation. AB - Human skin-derived precursor cells are a multipotent stem cell population that resides within the dermis throughout adulthood. Human skin-derived precursor cells can be isolated, purified, and expanded in large quantities from any patient, in health and disease, and differentiated to mesodermal and ectodermal cell types. Recently, it was also found that they can be directed towards hepatic cells with acquired properties of toxicological relevance. As such, they represent a valuable cell source for the further development of human-relevant in vitro models for the identification and quantification of hepatotoxic compounds. In this chapter, a robust basic methodology to isolate, expand, and differentiate human skin-derived precursor cells into hepatic cells in a sequential and time dependent way is provided. PMID- 26272136 TI - Establishment and Characterization of an In Vitro Model of Fas-Mediated Hepatocyte Cell Death. AB - Fas-mediated apoptosis underlies a plethora of liver pathologies and toxicities. As a consequence, this process is a major research topic in the field of experimental and clinical hepatology. The present chapter describes the setup of an in vitro model of hepatocellular apoptotic cell death. In essence, this system consists of freshly isolated hepatocytes cultured in a monolayer configuration, which are exposed to a combination of Fas ligand and cycloheximide. This in vitro model has been characterized by using a set of well-acknowledged cell death markers. This experimental system allows the study of the entire course of Fas mediated hepatocellular cell death, going from early apoptosis to secondary necrosis, and hence can serve a broad range of in vitro pharmaco-toxicological purposes. PMID- 26272139 TI - Generation of Hepatocytes from Pluripotent Stem Cells for Drug Screening and Developmental Modeling. AB - Hepatocytes produced from the differentiation of human pluripotent stem cells can be used to study human development and liver disease, to investigate the toxicological response of novel drug candidates, and as an alternative source of primary cells for transplantation therapies. Here, we describe a method to produce hepatocytes by differentiating human pluripotent stem cells into definitive endoderm, patterning definitive endoderm into anterior definitive endoderm, specifying anterior definitive endoderm into hepatic endoderm, and differentiating hepatic endoderm into immature hepatocytes. These cells are further matured in either two-dimensional or three-dimensional culture conditions to produce cells capable of metabolizing xenobiotics and generating liver specific proteins, such as albumin and alpha 1 antitrypsin. PMID- 26272134 TI - Immortalized Human Hepatic Cell Lines for In Vitro Testing and Research Purposes. AB - The ubiquitous shortage of primary human hepatocytes has urged the scientific community to search for alternative cell sources, such as immortalized hepatic cell lines. Over the years, several human hepatic cell lines have been produced, whether or not using a combination of viral oncogenes and human telomerase reverse transcriptase protein. Conditional approaches for hepatocyte immortalization have also been established and allow generation of growth controlled cell lines. A variety of immortalized human hepatocytes have already proven useful as tools for liver-based in vitro testing and fundamental research purposes. The present chapter describes currently applied immortalization strategies and provides an overview of the actually available immortalized human hepatic cell lines and their in vitro applications. PMID- 26272140 TI - Differentiation-Promoting Medium Additives for Hepatocyte Cultivation and Cryopreservation. AB - Isolated primary hepatocytes are considered as the reference system for in vitro hepatic methods. Following the isolation of primary hepatocytes from liver tissue, an unfavorable process named dedifferentiation is initiated leading to the attenuation of the hepatocellular phenotype both at the morphological and functional level. Freshly isolated hepatocytes can be used immediately or can be cryopreserved for future purposes. Currently, a number of antidedifferentiation strategies exist to extend the life span of isolated hepatocytes. The addition of differentiation-promoting compounds to the hepatocyte culture medium is the oldest and simplest antidedifferentiation approach applied. In the present chapter, the most commonly used medium additives for cultivation and cryopreservation of primary hepatocytes are reviewed. PMID- 26272141 TI - Coculture and Long-Term Maintenance of Hepatocytes. AB - The liver is the largest internal organ in mammals, serving a wide spectrum of vital functions. Loss of liver function due to drug toxicity, progressive fatty liver disease, or viral infection is a major cause of death in the United States of America. Pharmaceutical and cosmetic toxicity screening, basic research and the development of bioartificial liver devices require long-term hepatocyte culture techniques that sustain hepatocyte morphology and function. In recent years, several techniques have been developed that can support high levels of liver-specific gene expression, metabolic function, and synthetic activity for several weeks in culture. These include the collagen double gel configuration, hepatocyte spheroids, coculture with nonparenchymal cells, and micropatterned cocultures. This chapter will cover the current status of hepatocyte culture techniques, including media formulation, oxygen supply, and heterotypic cell-cell interactions. PMID- 26272142 TI - Primary Hepatocytes in Sandwich Culture. AB - Hepatocytes in sandwich configuration constitute of primary hepatocytes cultured between two layers of extracellular matrix. Sandwich-cultured hepatocytes maintain expression of liver-specific proteins and gradually form intact bile canaliculi with functional biliary excretion of endogenous compounds and xenobiotics. Both freshly isolated and cryopreserved hepatocytes can be used to establish sandwich cultures. Therefore, this preclinical model has become an invaluable in vitro tool to evaluate hepatobiliary drug transport, metabolism, hepatotoxicity, and drug interactions. In this chapter, commonly used procedures to cultivate primary hepatocytes from human and rat in sandwich configuration are described. PMID- 26272144 TI - Epigenetic Modifications as Antidedifferentiation Strategy for Primary Hepatocytes in Culture. AB - A well-known problem of cultured primary hepatocytes is their rapid dedifferentiation. During the last years, several strategies to counteract this phenomenon have been developed, of which changing the in vitro environment is the most popular one. However, mimicking the in vivo setting in vitro by adding soluble media additives or the restoration of both cell-cell and cell extracellular matrix contacts is not sufficient and only delays the dedifferentiation process instead of counteracting it. In this chapter, new strategies to prevent the deterioration of the liver-specific phenotype of primary hepatocytes in culture by targeting the (epi)genetic mechanisms that drive hepatocellular gene expression are described. PMID- 26272143 TI - Establishing Liver Bioreactors for In Vitro Research. AB - In vitro systems that can effectively model liver function for long periods of time are fundamental tools for preclinical research. Nevertheless, the adoption of in vitro research tools at the earliest stages of drug development has been hampered by the lack of culture systems that offer the robustness, scalability, and flexibility necessary to meet industry's demands. Bioreactor-based technologies, such as stirred tank bioreactors, constitute a feasible approach to aggregate hepatic cells and maintain long-term three-dimensional cultures. These three-dimensional cultures sustain the polarity, differentiated phenotype, and metabolic performance of human hepatocytes. Culture in computer-controlled stirred tank bioreactors allows the maintenance of physiological conditions, such as pH, dissolved oxygen, and temperature, with minimal fluctuations. Moreover, by operating in perfusion mode, gradients of soluble factors and metabolic by products can be established, aiming at resembling the in vivo microenvironment. This chapter provides a protocol for the aggregation and culture of hepatocyte spheroids in stirred tank bioreactors by applying perfusion mode for the long term culture of human hepatocytes. This in vitro culture system is compatible with feeding high-throughput screening platforms for the assessment of drug elimination pathways, being a useful tool for toxicology research and drug development in the preclinical phase. PMID- 26272145 TI - Transfection of Primary Hepatocytes with Liver-Enriched Transcription Factors Using Adenoviral Vectors. AB - Primary cultured hepatocytes are probably the best model to study endogenous metabolic pathways, toxicity, or drug metabolism. Many of these studies require expression of ectopic genes. It would be desirable to use a method of transfection that allows dose-response studies, high efficiency of transfection, and the possibility to express several genes at the same time. Adenoviral vectors fulfill these requirements, becoming a valuable tool for primary hepatocyte transfection. Moreover, they are easy to generate and do not require a high level of biocontainment. In the present chapter, we describe the generation, cloning, amplification, and purification of an adenoviral vector capable of infecting primary cultured hepatocytes. This recombinant adenovirus induces robust expression of the protein of interest in hepatocytes within a wide range of doses. PMID- 26272147 TI - Global MicroRNA Analysis in Primary Hepatocyte Cultures. AB - MicroRNAs are small non-coding molecules that regulate gene expression and in return affect diverse biological functions, including those involved in toxicity and development of disease. Recent evidence suggests that microRNAs play an important role in liver pathologies, like viral hepatitis, alcoholic liver, hepatocellular carcinoma, or drug-induced liver injury. Furthermore, numerous studies demonstrated the high potential of microRNAs as promising non-invasive biomarkers of liver disease or as relevant targets for therapeutic treatment. This chapter describes a method for global microRNA analysis of primary hepatocytes by high-throughput sequencing. The method comprises the isolation of high-quality total RNA, analysis of microRNA sequencing data, and the validation of the findings by reverse transcriptase quantitative polymerase chain reaction analysis. PMID- 26272146 TI - Transcriptomics of Hepatocytes Treated with Toxicants for Investigating Molecular Mechanisms Underlying Hepatotoxicity. AB - Transcriptomics is a powerful tool for high-throughput gene expression profiling. Transcriptome microarray experiments conducted with RNA isolated from hepatocytes after exposure to toxicants enable a deep insight into the molecular mechanisms of hepatotoxicity. This understanding, along with structure-activity relationships underlying hepatotoxicity, will provide a novel strategy to design cost-effective and safer therapeutics. Transcriptomics studies conducted with established hepatotoxic drugs in various in vitro and in vivo hepatotoxicity test systems have contributed to the elucidation of the mechanistic basis of liver insults, which were later on substantiated at the proteomics and metabolomics levels. The present chapter is focused on comprehensive transcriptomics of cultured primary hepatocytes treated with chemicals by applying Affymetrix microarray technology. It also describes the detailed protocol for culturing of hepatocytes, their exposure to toxicants as well as sample collection, including RNA isolation, RNA target preparation and finally the hybridization to gene chips for microarray expression analysis. PMID- 26272148 TI - Mass Spectrometry-Based Proteomics for Relative Protein Quantification and Biomarker Identification in Primary Human Hepatocytes. AB - Liquid chromatography-tandem mass spectrometry-based proteomics is a highly sensitive and effective tool to identify and quantify potential biomarkers in repeated dose toxicity studies using primary cell culture systems. In this respect, 8-plex isobaric tag for relative and absolute quantification labeling is the method of choice for relative quantification. After cell lysis and tryptic protein digestion, an individual isobaric tag is added to the amine groups of arginine and lysine. Then, up to eight differentially labeled samples are mixed and analyzed together in a mass spectrometry experiment. During peptide fragmentation in the mass spectrometer, the individual tag intensity of each identified peptide could be detected, reflecting the peptide intensities in the eight samples. The identified peptides are matched to their specific protein using specific search engines and finally to eight individual relative protein quantities. The two-dimensional fractionation of complex peptide mixtures minimizes the possibility of co-fragmentation of peptides from different origin in the mass spectrometer, which leads to a higher number of peptide search matches and therefore to better identification and quantification results. PMID- 26272150 TI - Measurement of Cytochrome P450 Enzyme Induction and Inhibition in Human Hepatoma Cells. AB - Cytochrome P450 enzymes are a diverse group of catalytic enzymes in the liver that are mainly responsible for the biotransformation of organic substances. Cytochrome P450 activity as well as both its induction and inhibition are key factors in drug biotransformation and can be involved in deactivation, activation, detoxification and toxification processes. Thus, the modulation of cytochrome P450 activity is an important parameter when evaluating the potential toxicity of chemical compounds using an in vitro system. The cytochrome P450 3A subfamily proteins are among the most important drug-metabolizing enzymes in human liver and are responsible for about half of all cytochrome P450-dependent drug oxidations. In vitro, these enzymes are active not only in primary human hepatocyte cultures, but also in differentiated human hepatoma HepaRG cells. The present protocol describes the culture of cryopreserved differentiated HepaRG cells and the evaluation of its cytochrome P450 activity upon exposure to a chemical compound using a commercially available luminogenic cytochrome P450 assay. This in vitro model can be used to monitor the induction and inhibition of cytochrome P450 3A following exposure to a particular test compound. PMID- 26272149 TI - Targeted Metabolomics for Homocysteine-Related Metabolites in Primary Hepatocytes. AB - Liquid chromatography-tandem mass spectrometry has become the most convenient method to identify and quantify low molecular weight metabolites from various sources. Metabolomics studies of hepatocytes hold promise for the identification of the mechanisms of toxicant-related disease processes. In this chapter, we present a rapid and sensitive liquid chromatography-tandem mass spectrometry method for the quantification of intracellular concentrations of nine homocysteine-based metabolites, namely homocysteine, methionine, cysteine, dimethylglycine, cystathionine, S-adenosylmethionine, S-adenosylhomocysteine, choline, and betaine. The method is specifically designed for the analysis of cultured primary hepatocytes. PMID- 26272152 TI - Measurement of Albumin Secretion as Functionality Test in Primary Hepatocyte Cultures. AB - One of the most important functions of hepatocytes is the synthesis of serum proteins, more specifically of serum albumin. Albumin secretion in serum is essential, since it maintains the oncotic pressure in the body. Measurement of albumin secretion is used as a liver function test to indicate potential liver injury and liver pathology. In this chapter, a protocol for the measurement of albumin secretion in the supernatant of cultured rat hepatocytes is described. The procedure relies on an enzyme-linked immunosorbent assay allowing rat albumin to be quantitatively measured. PMID- 26272151 TI - Analysis of Sinusoidal Drug Uptake Transporter Activities in Primary Human Hepatocytes. AB - Hepatic drug transporters play an important role in pharmacokinetics and drug drug interactions. Among these membrane transporters, the sodium taurocholate cotransporting polypeptide (NTCP/SLC10A1), the organic anion transporting polypeptides (OATPs) 1B1 (SLCO1B1), 1B3 (SLCO1B3) and 2B1 (SLCO2B1), the organic anion transporter 2 (OAT2/SLC22A7) and the organic cation transporter 1 (OCT1/SLC22A1) are likely major ones, notably mediating sinusoidal uptake of various drugs or endogenous compounds, like bile acids, from blood into hepatocytes. Studying putative interactions of drugs, including those in development processes, with these transporters is an important issue. For this purpose, cultured human hepatocytes, that exhibit functional expression of NTCP, OATPs, OAT2 and OCT1, are considered as a relevant in vitro cellular model. This chapter describes a method allowing to accurately analyze NTCP, OATP, OAT2 and OCT1 transport activities in primary human hepatocyte cultures, which can be applied to the determination of potential interactions of drugs with these hepatic uptake transporters. PMID- 26272153 TI - Measurement of Blood Coagulation Factor Synthesis in Cultures of Human Hepatocytes. AB - An important function of the liver is the synthesis and secretion of blood coagulation factors. Within the liver, hepatocytes are involved in the synthesis of most blood coagulation factors, such as fibrinogen, prothrombin, factor V, VII, IX, X, XI, XII, as well as protein C and S, and antithrombin, whereas liver sinusoidal endothelial cells produce factor VIII and von Willebrand factor. Here, we describe methods for the detection and quantification of most blood coagulation factors in hepatocytes in vitro. Hepatocyte cultures indeed provide a valuable tool to study blood coagulation factors. In addition, the generation and expansion of hepatocytes or hepatocyte-like cells may be used in future for cell based therapies of liver diseases, including blood coagulation factor deficiencies. PMID- 26272154 TI - Functionality Testing of Primary Hepatocytes in Culture by Measuring Urea Synthesis. AB - One of the mechanisms of healthy hepatocytes to detoxify ammonia in the liver consists of converting it into urea. When liver function is impaired, this detoxification capacity decreases and may cause severe pathologies, such as hepatic encephalopathy. Consequently, urea synthesis is a parameter that can be used to monitor liver functionality. In this chapter, a protocol for the measurement of urea synthesis in the culture medium of cultured rat hepatocytes is described. The procedure relies on a chromogenic reagent that specifically forms a colored complex with urea. The latter can be measured colorimetrically and is directly proportional to the urea concentration in the sample. PMID- 26272155 TI - Assay of Bile Acid Conjugation and Excretion in Human Hepatocytes. AB - Primary hepatocytes isolated from human, mouse and rat liver as well as cell lines, such as HepG2 cells, are frequently used in vitro systems in liver research. In regenerative medicine, stem cells are used for differentiation towards hepatocyte-like cells with the goal of creating differentiated functional hepatocytes. It is therefore important to measure the quality and function of highly specialized hepatocyte-specific functions using appropriate methods. In this chapter, we describe an assay to assess conjugation and excretion of labeled bile acids in cultured hepatocytes. PMID- 26272156 TI - General Cytotoxicity Assessment by Means of the MTT Assay. AB - Cytotoxicity assays were among the first in vitro bioassay methods used to predict toxicity of substances to various tissues. In vitro cytotoxicity testing provides a crucial means for safety assessment and screening, and for ranking compounds. The choice of using a particular cytotoxicity assay technology may be influenced by specific research goals. As such, four main classes of assays are used to monitor the response of cultured cells after treatment with potential toxicants. These methods measure viability, cell membrane integrity, cell proliferation, and metabolic activity. In this chapter, we focus on the 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium reduction colorimetric assay to evaluate detrimental intracellular effects on metabolic activity. This assay is well-characterized, simple to use and remains popular in several laboratories worldwide. PMID- 26272157 TI - Measurement of Apoptotic and Necrotic Cell Death in Primary Hepatocyte Cultures. AB - Hepatotoxicity, including drug-induced liver injury, is frequently accompanied by cell death. The latter is typically driven by apoptosis or necrosis, which substantially differ based upon biochemical and morphological criteria. This chapter describes two commonly used methods to probe apoptotic and necrotic activities in adherent monolayer cultures of primary hepatocytes. The apoptosis assay uses a prototypical substrate of caspase 3, the main executor of apoptotic cell death, which can be cleaved, yielding a product that can be measured fluorimetrically. The second assay relies on the disruption of the cell plasma membrane, which typically occurs in necrotic cell death and that results in the extracellular release of cytoplasmic enzymes, such as lactate dehydrogenase. The latter can be indirectly assessed by spectrophotometrically measuring the consumption of reduced nicotinamide adenine dinucleotide. PMID- 26272159 TI - In Vitro Cell Culture Models of Hepatic Steatosis. AB - The liver is the systemic hub of lipid metabolism. The excessive accumulation of lipids in hepatocytes, steatosis, is a major clinical concern, whose progressive forms lead to end-stage liver disease. Currently, animal studies are the gold standard in toxicological risk assessment. Fueled by an integration of modern omics technologies, in silico models and in vitro system optimization, a new paradigm in the basis for toxicological risk assessment is emerging away from the use of animals. In recent years, in vitro assays have been developed for the early screening of the steatogenic potential of compounds. The present chapter describes an assay for the intracellular detection of lipids, a high-content screen for the distinction between steatosis and phospholipidosis, a multiparametric high-content screen for steatogenic potential and a liver X receptor reporter cell line. PMID- 26272158 TI - Critical Factors in the Assessment of Cholestatic Liver Injury In Vitro. AB - Cholestasis is a common pathological component of numerous liver diseases. The initiating event during cholestatic liver injury is widely believed to be the accumulation of bile acids in hepatocytes and the hepatic parenchyma. As bile acids are considered the primary toxic compounds in the injury, numerous in vitro models of bile acid-induced injury and bile acid-induced changes in gene expression have been developed to attempt to better define cholestasis at a cellular level. This chapter focuses on the establishment of a system for determining the effects of cholestatic concentrations of bile acids on hepatocytes using primary hepatocytes or hepatoma cell lines. Moreover, this chapter addresses significant differences in the response of different species to bile acid exposure and novel information on the relevance of treating hepatocytes with concentrations of specific bile acids. PMID- 26272160 TI - Assessment of Liver Fibrotic Insults In Vitro. AB - In vitro systems are required to evaluate potential liver fibrogenic effects of drugs and compounds during drug development and toxicity screening, respectively. Upon liver injury or toxicity, hepatic stellate cells are activated, thereby acquiring a myofibroblastic phenotype and participating in extracellular matrix deposition and liver fibrosis. The most widely used in vitro models to investigate liver fibrogenesis are primary cultures of hepatic stellate cells, which can be isolated from healthy human livers. Currently, there are no effective methods to maintain hepatic stellate cells in vitro in a quiescent phenotype. Therefore, when cells are plated, they spontaneously become activated in few days. Most in vitro studies in this area have been performed with monocultures of hepatic stellate cells in order to assess the direct effects of a given factor on hepatic stellate cell activation or the induction of inflammatory and fibrogenic responses. In this chapter, focus is put on basic protocols to isolate hepatic stellate cells from human tissue and to maintain them in culture as well as on common in vitro assays to evaluate their response to profibrogenic factors. PMID- 26272162 TI - Direct probing of contact electrification by using optical second harmonic generation technique. AB - Contact electrification between two different materials is one of the oldest fields of study in solid-state physics. Here, we introduced an innovative system based on optical electric-field-induced second harmonic generation (EFI-SHG) technique that can directly monitor the dynamic performance of the contact electrification on the surface of polyimide film. After the contact, the EFI-SHG system visualized briefly three relaxations of the tribo-induced charges on the surface of a polyimide film, a fast relaxation within 3 min followed by two much slower relaxations, which were possibly related to different charge diffusion routes. The contact electrification under several special experimental conditions (wind, water and steam) was studied to demonstrate the high flexibility and material selectivity of the EFI-SHG. The EFI-SHG studies confirmed the motion of the water can remove the surface charge, while the appearance and the evaporation of a thin water layer cannot enhance the charge diffusion. We anticipate that this experimental technique will find a variety of applications in the field of contact electrification and the development of the recently invented triboelectric nano generator. PMID- 26272161 TI - Density and growth rates of spider mites in relation to phenological stages of soybean cultivars in Brazil. AB - The population fluctuations of spider mites on different soybean cultivars were studied in two experiments performed in the municipalities of Sao Sepe (experiment 1) and Santa Maria (experiment 2) in the state of Rio Grande do Sul, Brazil. The number of cultivars was 20 in Sao Sepe and 25 in Santa Maria, and at each location leaves were sampled from 15 plants per cultivar every week throughout the entire plant developmental cycle, amounting to 11 and 10 samplings in experiment 1 and 2, respectively. The statistical analysis revealed that mite densities varied significantly with cultivar and time. Besides, the interaction between soybean cultivars and sampling times was significant at both locations. This indicates that the populations did not vary in the same way among cultivars over time, which is attributed to differences among the cultivars with respect to their phenology and response to spider mites. Equations for describing the mite population dynamics were estimated for each cultivar, mostly by fitting cubic equations to the weekly growth rates (per capita changes) in mite densities. We also found that the highest growth rates for mites on soybean cultivars in both locations occurred after the beginning of flowering, when the plants shifted from the vegetative to reproductive stages, about 3 weeks before reaching the peak densities. PMID- 26272163 TI - Understanding the Experiences of Rural Community-Dwelling Older Adults in Using a New DVD-Delivered Otago Exercise Program: A Qualitative Study. AB - BACKGROUND: The home-based Otago Exercise Program (OEP) has been shown to reduce the occurrence of falls in community-dwelling seniors. A new OEP DVD was recently developed for people living in rural communities to be used with minimal coaching by a physical therapist. OBJECTIVE: This study aimed to understand older adults' experiences using the DVD-delivered OEP and explore barriers and facilitators to implementing the DVD-delivered OEP from the participants' perspectives. METHODS: Rural community-dwelling older adults (75 years and older) who participated in a six-month DVD-delivered OEP study were invited to participate in this qualitative study. Two small group interviews were initially conducted to explore the breadth of participants' experiences with the program. These were followed by semi structured individual interviews to gain an in-depth understanding of these experiences. An inductive constant comparison analysis of the transcripts was performed. To ensure methodological rigor, field notes, journaling, and an audit trail were maintained, supplemented by peer-review. RESULTS: Of 32 eligible participants, five participated in group interviews and 16 in individual interviews. Three themes emerged. Theme 1, The OEP DVD-useful training tool but in need of more pep, represented participants' experiences that the DVD provided important guidance at program onset, but was too slow and low-energy for longer term use. Theme 2, Gaining control over one's exercise regimen, but sometimes life gets in the way of staying active, described participants' appreciation of the program's flexibility, but personal health concerns and everyday lives posed challenges to adhering to the program. Theme 3, Social creatures-wanting greater human connection during exercise, described how some participants desired further social interactions for enhancing motivation and receiving guidance. CONCLUSIONS: Individuals should be encouraged to refer to the OEP user manual or DVD as needed and engage friends and family in exercises. The importance of exercise even when living with health problems should be raised at program onset, and participants should be supported in working through challenging issues. Health professionals should work with individuals to integrate the program with their everyday activities. PMID- 26272164 TI - Do extant elephants have superior canal dehiscence syndrome? AB - CONCLUSION: X-ray CT of an Asian elephant's skull suggest that elephants do not have a labyrinthine 3(rd) mobile window. This excludes the concept that elephants benefit from enhancement of bone conducted vibration by an extra opening of the labyrinth. This finding does not, however, exclude that elephants use bone conducted hearing for seismic detection, nor that other species may use an extra labyrinthine opening for improved detection of seismic signals. OBJECTIVES: In man, a pathologic extra opening of the bony labyrinth causes altered hearing with supranormal bone conduction. Theoretically, this variation in auditory performance could be advantageous for detection of seismic waves. METHOD: The skull of an adult Asian elephant was examined by X-ray computed tomography to investigate whether a natural '3(rd) mobile window' mechanism for enhanced sensitivity of body sounds exist in elephants. RESULTS: Although the entire elephant's skull was otherwise broadly aerated, the labyrinth areas were surrounded by dense bone. PMID- 26272165 TI - Optimal moderator materials at various proton energies considering photon dose rate after irradiation for an accelerator-driven 9Be(p, n) boron neutron capture therapy neutron source. AB - We evaluated the accelerator beam power and the neutron-induced radioactivity of (9)Be(p, n) boron neutron capture therapy (BNCT) neutron sources having a MgF2, CaF2, or AlF3 moderator and driven by protons with energy from 8 MeV to 30 MeV. The optimal moderator materials were found to be MgF2 for proton energies less than 10 MeV because of lower required accelerator beam power and CaF2 for higher proton energies because of lower photon dose rate at the treatment position after neutron irradiation. PMID- 26272166 TI - Positron annihilation lifetime studies of changes in free volume on some biorelevant nitrogen heterocyclic compounds and their S-glycosylation. AB - A series of N-heterocyclic compounds was investigated by positron annihilation lifetime spectroscopy as well as Doppler broadening of annihilation radiation (DBAR) at room temperature. The results showed that the formation probability and life time of ortho-positronium in this series are structure and electron-donation character dependent, and can give more information about the structure. The DBAR provides direct information about the change of core and valance electrons as well as the number of defect types present in these compounds. PMID- 26272167 TI - "Now I see it, now I don't": Determining Threshold Levels of Facial Emotion Recognition for Use in Patient Populations. AB - The importance of including measures of emotion processing, such as tests of facial emotion recognition (FER), as part of a comprehensive neuropsychological assessment is being increasingly recognized. In clinical settings, FER tests need to be sensitive, short, and easy to administer, given the limited time available and patient limitations. Current tests, however, commonly use stimuli that either display prototypical emotions, bearing the risk of ceiling effects and unequal task difficulty, or are cognitively too demanding and time-consuming. To overcome these limitations in FER testing in patient populations, we aimed to define FER threshold levels for the six basic emotions in healthy individuals. Forty-nine healthy individuals between 52 and 79 years of age were asked to identify the six basic emotions at different intensity levels (25%, 50%, 75%, 100%, and 125% of the prototypical emotion). Analyses uncovered differing threshold levels across emotions and sex of facial stimuli, ranging from 50% up to 100% intensities. Using these findings as "healthy population benchmarks", we propose to apply these threshold levels to clinical populations either as facial emotion recognition or intensity rating tasks. As part of any comprehensive social cognition test battery, this approach should allow for a rapid and sensitive assessment of potential FER deficits. PMID- 26272168 TI - A miR-130a-YAP positive feedback loop promotes organ size and tumorigenesis. AB - Organ size determination is one of the most intriguing unsolved mysteries in biology. Aberrant activation of the major effector and transcription co-activator YAP in the Hippo pathway causes drastic organ enlargement in development and underlies tumorigenesis in many human cancers. However, how robust YAP activation is achieved during organ size control remains elusive. Here we report that the YAP signaling is sustained through a novel microRNA-dependent positive feedback loop. miR-130a, which is directly induced by YAP, could effectively repress VGLL4, an inhibitor of YAP activity, thereby amplifying the YAP signals. Inhibition of miR-130a reversed liver size enlargement induced by Hippo pathway inactivation and blocked YAP-induced tumorigenesis. Furthermore, the Drosophila Hippo pathway target bantam functionally mimics miR-130a by repressing the VGLL4 homolog SdBP/Tgi. These findings reveal an evolutionarily conserved positive feedback mechanism underlying robustness of the Hippo pathway in size control and tumorigenesis. PMID- 26272169 TI - Longitudinal relationship between insulin-like growth factor-1 levels and vertical facial growth. AB - BACKGROUND: Facial growth in the vertical dimension is the last to be completed and can often be detrimental to the success of dental implants, orthodontic treatment, and orthognathic surgery that young individuals undergo. AIM: The purpose of this study was to evaluate the longitudinal relationship between changes in total anterior facial height and insulin-like growth factor-1 (IGF-1) levels measured using blood-spot samples. METHODS: Our sample included 25 orthodontic patients from whom we had access to annual lateral cephalometric radiographs and IGF-1 measurements. Each subject was observed between 2 and 6 times, resulting in 43 annual intervals from a total of 77 observations. RESULTS: We noted a significant moderate positive correlation (+ 0.48) between the percentage of change in blood-spot IGF-1 levels and the percentage of change in total anterior face height (p = 0.01). CONCLUSION: Longitudinal changes in IGF-1 levels can be used to predict a patient's vertical facial growth. There was no significant correlation between changes in vertical facial development and a single cross-sectional IGF-1 measurement. PMID- 26272170 TI - Pain reduced by low-level laser therapy during use of orthodontic separators in early mixed dentition. AB - OBJECTIVE: The purpose of this work was to investigate whether low-level laser therapy (LLLT) applied at a defined distance from the gingiva has a pain-reducing effect in young patients undergoing orthodontic separation during the early mixed dentition stage. MATERIALS AND METHODS: A total of 40 children in early mixed dentition (mean age 8.05 years) who required separation of molars were included. The study comprised a group of 20 patients whose treatment included laser application on the day of separation and a control group of 20 patients not receiving LLLT. All patients recorded their maximum pain intensities on the day of separation (day 1) and on the following 4 days. RESULTS: Compared to the control group, pain perception was significantly reduced (p < 0.05) in the LLLT group on day 1 and continued to be reduced on day 2. Equivalent pain levels were recorded in both groups on days 3-5. CONCLUSION: Given our findings of a pain reducing effect in young patients undergoing orthodontic separation during the early mixed-dentition stage, LLLT is an interesting alternative option of providing analgesia even in very young patients. PMID- 26272172 TI - Transcriptome profiling of larvae of the marine medaka Oryzias melastigma by Illumina RNA-seq. AB - We sequenced the whole transcriptome of the 24h-old larval stage of the marine medaka Oryzias melastigma using Illumina RNA-seq. De novo assembly of 64,914,324 raw reads was performed using Trinity, resulting in 144,953 contigs. TransDecoder found 58,246 candidate coding contigs with homology to other species based on BLAST analysis. Functional gene annotation was performed by GO, KEGG pathway, and COG analyses. We determined an expressed gene catalog for O. melastigma for gene information-based environmental genomic and ecotoxicogenomic research. This information will serve as a resource for elucidating the molecular mechanisms underlying the response of O. melastigma to environmental stresses and chemicals. PMID- 26272171 TI - A novel mutation in NCF2 associated with autoimmune disease and a solitary late onset infection. AB - Chronic granulomatous disease (CGD) is typically characterized by recurrent infections, granulomatous disease, and an increased susceptibility to autoimmune disease. We report a novel homozygous mutation in NCF2 that permits residual expression of an alternatively spliced variant in a patient with duodenitis and systemic lupus erythematosus (SLE), followed by a late-onset, single pulmonary infection in the setting of immunosuppressive medications. This report highlights the importance of considering CGD in patients who present initially exclusively with autoimmune disease. PMID- 26272173 TI - Effect of subcutaneous insulin detemir on glucose flux, lipolysis and electroencephalography in type 1 diabetes. AB - The aim of the present study was to investigate the effects of subcutaneous detemir on glucose flux, lipid metabolism and brain function. Twelve people with type 1 diabetes received, in random order, 0.5 units/kg body weight detemir or NPH insulin. Glucose concentration was clamped at 5 mmol/l then increased to 10 mmol/l. Glucose production rate (glucose Ra), glucose uptake (glucose Rd) and glycerol production (glycerol Ra) were measured with a constant intravenous infusion of [6,6(2) H(2)]glucose and [(2)H(5)]glycerol. Electroencephalography direct current (DC) and alternating current (AC) potentials were measured. While detemir induced similar effects on glucose Ra, glucose Rd and glycerol Ra during euglycaemia compared with NPH, it triggered a distinct negative shift in DC potentials, with a significant treatment effect in frontal cerebrocortical channels (p < 0.001). AC spectral power showed significant differences in theta and alpha frequencies during euglycaemia (p = 0.03). Subcutaneous detemir exerts different effects on brain function when compared with NPH in people with type 1 diabetes. This may be an important mechanism behind the limitation of weight gain with detemir. PMID- 26272174 TI - An assessment of randomized controlled trials (RCTs) for non-communicable diseases (NCDs): more and higher quality research is required in less developed countries. AB - Research is crucial to implement evidence-based health interventions for control of non-communicable diseases (NCDs). This study aims to assess main features of randomized controlled trials (RCTs) for control of NCDs, and to identify gaps in clinical research on NCDs between high-income and less developed countries. The study included 1177 RCTs in 82 Cochrane Systematic reviews (CSRs) and evaluated interventions for adults with hypertension, diabetes, stroke, or heart diseases. Multivariate logistic regression analyses were conducted to explore factors associated with risk of bias in included RCTs. We found that 78.2% of RCTs of interventions for major NCDs recruited patients in high-income countries. The number of RCTs included in the CSRs was increasing over time, and the increasing speed was more noticeable for RCTs conducted in middle-income countries. RCTs conducted in less developed countries tended to be more recently published, less likely to be published in English, with smaller sample sizes, and at a higher risk of bias. In conclusion, there is still a lack of research evidence for control of NCDs in less developed countries. To brace for rising NCDs and avoid waste of scarce research resources, not only more but also higher quality clinical trials are required in low-and-middle-income countries. PMID- 26272175 TI - Gut microbiota modulate the immune effect against hepatitis B virus infection. AB - The immunological mechanisms by which hepatitis B virus (HBV) initiates and maintains acute or chronic infection, even the formation of cirrhosis and hepatocellular carcinoma, are still undefined. An increasing number of studies have shown that intestinal flora regulate immune homeostasis, and, thus, protect the immunologic function against hepatitis virus infection. In this article, we discuss gut microbiota and its potential immune effects against HBV infection. It may provide a novel insight into the pathogenesis of HBV infection, as well as a potential therapeutic target to HBV-related disease. PMID- 26272177 TI - Breed differences in development of anti-insulin antibodies in diabetic dogs and investigation of the role of dog leukocyte antigen (DLA) genes. AB - Administration of insulin for treatment of diabetes mellitus in dogs can stimulate an immune response, with a proportion of animals developing anti insulin antibodies (AIA). For an IgG antibody response to occur, this would require B cell presentation of insulin peptides by major histocompatibility complex (MHC) class II molecules, encoded by dog leukocyte antigen (DLA) genes, in order to receive T-cell help for class switching. DLA genes are highly polymorphic in the dog population and vary from breed to breed. The aim of the present study was to evaluate AIA reactivity in diabetic dogs of different breeds and to investigate whether DLA genes influence AIA status. Indirect ELISA was used to determine serological reactivity to insulin in diabetic dogs, treated with either a porcine or bovine insulin preparation. DLA haplotypes for diabetic dogs were determined by sequence-based typing of DLA-DRB1, -DQA1 and -DQB1 loci. Significantly greater insulin reactivity was seen in treated diabetic dogs (n=942) compared with non-diabetic dogs (n=100). Relatively few newly diagnosed diabetic dogs (3/109) were found to be AIA positive, although this provides evidence that insulin autoantibodies might be involved in the pathogenesis of the disease in some cases. Of the diabetic dogs treated with a bovine insulin preparation, 52.3% (182/348) were AIA positive, compared with 12.6% (75/594) of dogs treated with a porcine insulin preparation, suggesting that bovine insulin is more immunogenic. Breeds such as dachshund, Cairn terrier, miniature schnauzer and Tibetan terrier were more likely to develop AIA, whereas cocker spaniels were less likely to develop AIA, compared with crossbreed dogs. In diabetic dogs, DLA haplotype DRB1*0015--DQA1*006--DQB1*023 was associated with being AIA positive, whereas the haplotype DLA-DRB1*006--DQA1*005--DQB1*007 showed an association with being AIA negative. These research findings suggest that DLA genes influence AIA responses in treated diabetic dogs. PMID- 26272176 TI - Invasive Fusobacterium necrophorum infections and Lemierre's syndrome: the role of thrombophilia and EBV. AB - The purpose of this investigation was to describe the clinical spectrum of invasive Fusobacterium necrophorum infections and Lemierre's syndrome, to examine the role of underlying thrombophilia and concomitant mononucleosis in Lemierre's syndrome, and to describe thromboembolic complications. Patients with invasive F. necrophorum infections were identified either prospectively or retrospectively through the regional database of clinical microbiology from 2000 to 2015. Patient records were reviewed and blood samples from patients with Lemierre's syndrome were collected for Epstein-Barr virus (EBV) serology and screening for thrombophilia. Of the 65 patients included, 33 had Lemierre's syndrome. Of the remaining 32 patients, other infections of the respiratory tract and abdominal or urogenital infections were most common. Patients with Lemierre's syndrome or other tonsillar infections were younger than patients from the other groups. For Lemierre's syndrome, the 26 patients with severe sepsis on admittance had longer duration of symptoms. Three of five patients who developed distant manifestations had more than 14 days of symptoms. Jugular vein thrombosis was verified in 14 patients, two of whom developed serious complications. Three of 26 patients tested had factor V Leiden mutation, corresponding to the background prevalence. One of 22 patients tested had a concomitant EBV infection. This study confirms earlier studies of the clinical spectrum caused by F. necrophorum. For Lemierre's syndrome, the study adds to the knowledge on thromboembolic outcome, demonstrating that jugular vein thrombosis may cause severe complications. The time to treatment seems to be important for the risk of severe disease. In this study, concomitant EBV infection or underlying thrombophilia was uncommon. PMID- 26272178 TI - Low Socioeconomic Status is an Independent Risk Factor for Survival After Abdominal Aortic Aneurysm Repair and Open Surgery for Peripheral Artery Disease. AB - OBJECTIVE/BACKGROUND: The association between socioeconomic status (SES), presentation, and outcome after vascular surgery is largely unknown. This study aimed to determine the influence of SES on post-operative survival and severity of disease at presentation among vascular surgery patients in the Dutch setting of equal access to and provision of care. METHODS: Patients undergoing surgical treatment for peripheral artery disease (PAD), abdominal aortic aneurysm (AAA), or carotid artery stenosis between January 2003 and December 2011 were retrospectively included. The association between SES, quantified by household income, disease severity at presentation, and survival was studied using logistic and Cox regression analysis adjusted for demographics, and medical and behavioral risk factors. RESULTS: A total of 1,178 patients were included. Low income was associated with worse post-operative survival in the PAD cohort (n = 324, hazard ratio 1.05, 95% confidence interval [CI] 1.00-1.10, per 5,000 Euro decrease) and the AAA cohort (n = 440, quadratic relation, p = .01). AAA patients in the lowest income quartile were more likely to present with a ruptured aneurysm (odds ratio [OR] 2.12, 95% CI 1.08-4.17). Lowest income quartile PAD patients presented more frequently with symptoms of critical limb ischemia, although no significant association could be established (OR 2.02, 95% CI 0.96-4.26). CONCLUSIONS: The increased health hazards observed in this study are caused by patient related factors rather than differences in medical care, considering the equality of care provided by the study setting. Although the exact mechanism driving the association between SES and worse outcome remains elusive, consideration of SES as a risk factor in pre-operative decision making and focus on treatment of known SES related behavioral and psychosocial risk factors may improve the outcome of patients with vascular disease. PMID- 26272179 TI - Restricted Maximum Likelihood Estimation for Parameters of the Social Relations Model. AB - In many areas of research, the round-robin design is used to study interpersonal judgments and behaviors. The resulting data are analyzed with the social relations model (SRM), whereby almost all previously published studies have used ANOVA-based methods or multilevel-based methods to obtain SRM parameter estimates. In this article, the SRM is embedded into the linear mixed model framework, and it is shown how restricted maximum likelihood can be employed to estimate the SRM parameters. It is also described how the effect of covariates on the SRM-specific effects can be estimated. An example is presented to illustrate the approach. We also present the results of a simulation study in which the performance of the proposed approach is compared to the ANOVA method. PMID- 26272180 TI - Tumor microenvironment and cancer therapy resistance. AB - Innate resistance to various therapeutic interventions is a hallmark of cancer. In recent years, however, acquired resistance has emerged as a daunting challenge to anticancer treatments including chemotherapy, radiation and targeted therapy, which abolishes the efficacy of otherwise successful regimens. Cancer cells gain resistance through a variety of mechanisms in both primary and metastatic sites, involving cell intrinsic and extrinsic factors, but the latter often remains overlooked. Mounting evidence suggests critical roles played by the tumor microenvironment (TME) in multiple aspects of cancer progression particularly therapeutic resistance. The TME decreases drug penetration, confers proliferative and antiapoptotic advantages to surviving cells, facilitates resistance without causing genetic mutations and epigenetic changes, collectively modifying disease modality and distorting clinical indices. Recent studies have set the baseline for future investigation on the intricate relationship between cancer resistance and the TME in pathological backgrounds. This review provides an updated outline of research advances in TME biology and highlights the prospect of targeting the TME as an essential strategy to overcome cancer resistance and improve therapeutic outcomes through precise intervention. In the long run, continued inputs into translational medicine remain highly desired to achieve durable responses in the current era of personalized clinical oncology. PMID- 26272181 TI - The progress and prospects of routine prophylactic antiviral treatment in hepatitis B-related hepatocellular carcinoma. AB - Liver cancer is a common cancer and a leading cause of cancer-related deaths. Among all types of primary liver cancers, hepatocellular carcinoma (HCC) is the major histological subtype, and hepatitis B virus (HBV) infection is the leading cause of HCC. Treatments for hepatitis B related HCC include hepatectomy, liver transplantation, transarterial chemoembolization (TACE), ablative therapy, and Sorafenib treatment. However, HBV reactivation can occur in patients who receive these treatments, resulting in poor clinical outcomes. However, prophylactic antiviral treatment in patients with hepatitis B-related HCC, can reduce the copies of HBV DNA, prevent HBV reactivation, reduce hepatic inflammation, reverse liver fibrosis, decrease tumor recurrence and metastasis, and extend survival time. Prophylactic antiviral treatment should be routinely performed as an important adjuvant therapy in HBV-related HCC patients. PMID- 26272183 TI - Characteristics of liver cancer stem cells and clinical correlations. AB - Liver cancer is an aggressive malignant disease with a poor prognosis. Patients with liver cancer are usually diagnosed at an advanced stage and thus miss the opportunity for surgical resection. Chemotherapy and radiofrequency ablation, which target tumor bulk, have exhibited limited therapeutic efficacy to date. Liver cancer stem cells (CSCs) are a small subset of undifferentiated cells existed in liver cancer, which are considered to be responsible for liver cancer initiation, metastasis, relapse and chemoresistance. Elucidating liver CSC characteristics and disclosing their regulatory mechanism might not only deepen our understanding of the pathogenesis of liver cancer but also facilitate the development of diagnostic, prognostic and therapeutic approaches to improve the clinical management of liver cancer. In this review, we will summarize the recent advances in liver CSC research in terms of the origin, identification, regulation and clinical correlation. PMID- 26272182 TI - Tumor cell-secreted angiogenin induces angiogenic activity of endothelial cells by suppressing miR-542-3p. AB - Therapeutic strategies for targeting angiogenesis have been proven as successful treatments for divergent cancers. We previously discovered an anti-angiogenic miR 542-3p, which directly targeted the key angiogenesis-promoting protein Angiopoietin-2 to inhibit tumor angiogenesis in breast cancer models. In this study, to further investigate the mechanism of miR-542-3p induced angiogenic inhibition, we screened for tumor cell derived factors which were responsible for miR-542-3p alteration in endothelial cells. We found that tumor cell-derived angiogenin downregulated miR-542-3p in endothelial cells. Overexpression of angiogenin in tumor cells facilitated angiogenic activation in both in vitro and in vivo models via inhibition of miR-542-3p. Furthermore, our results showed that angiogenin could suppress CEBPB and POU2F1, which were transcription factors for miR-542-3p, suggesting a novel tumor cell-endothelial cell signal pathway. In addition, the level of angiogenin in primary breast carcinomas correlated with clinical progression. Serum levels of angiogenin were associated with metastatic development of breast cancer patients. Together, these findings reveal a novel regulatory pathway whereby tumor-derived angiogenin directly activates angiogenesis through inhibition of miR-542-3p, suggesting that angiogenin may represent a promising target for anti-angiogenic therapy and a potential marker for monitoring disease progression. PMID- 26272184 TI - Suppression of motor protein KIF3C expression inhibits tumor growth and metastasis in breast cancer by inhibiting TGF-beta signaling. AB - Breast cancer is the most common cause of death among women. KIF3C, a member of kinesin superfamily, functions as a motor protein involved in axonal transport in neuronal cells. To explore the expression, regulation and mechanism of KIF3C in breast cancer, 4 breast cancer cell lines and 93 cases of primary breast cancer and paired adjacent tissues were examined. Immunohistochemistry, Real Time Polymerase Chain Reaction (RT-PCR), Western blot, flow cytometry, short hairpin RNA (shRNA) interference, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation techniques and xenograft mice model were used. We found that KIF3C was over-expressed in breast cancer tissues and such high KIF3C expression was also associated with tumor recurrence and lymph node metastasis. Silencing of KIF3C by shRNA inhibited epithelial-mesenchymal transition and metastasis by inhibiting TGF-beta signaling and suppressed breast cancer cell proliferation through inducing G2/M phase arrest. The tumor size was smaller and the number of lung metastatic nodules was less in KIF3C depletion MDA-MB-231 cell xenograft mice than in negative control group. These results suggested that high expression of KIF3C in breast cancer may be associated with the tumor progression and metastasis. PMID- 26272186 TI - Strong textured SmCo5 nanoflakes with ultrahigh coercivity prepared by multistep (three steps) surfactant-assisted ball milling. AB - The high coercivity of 26.2 kOe for SmCo5 nanoflakes are obtained by multistep (three steps) surfactant-assisted ball milling. The magnetic properties, phase structure and morphology are studied by VSM, XRD and SEM, respectively. The results demonstrate that the three step ball-milling can keep more complete crystallinity (relatively less defects) during the process of milling compared with one step high energy ball-milling, which enhances the texture degree and coercivity. In addition, the mechanism of coercivity are also studied by the temperature dependence of demagnetization curves for aligned SmCo5 nanoflakes/resin composite, the result indicates that the magnetization reversal could be controlled by co-existed mechanisms of pinning and nucleation. PMID- 26272188 TI - Antiviral drugs: Novel antibodies defeat dengue virus. PMID- 26272187 TI - Novel Biomarker Approaches for Managing Patients With Cardiac Transplantation. AB - Despite major advances in the medical care of patients following heart transplantation (HTx) and a steady increase in long-term survival, allograft surveillance is still based on endomyocardial biopsy, the gold standard since the 1970s. This invasive procedure calls for less burdening and more cost-effective approaches. In recent years, impressive progress has been made in utilizing blood based biomarkers for the diagnosis and management of diseases in a variety of fields. Hence, a number of trials have been performed testing the usefulness of circulating molecules or other technical methods to overcome the need for surveillance myocardial biopsy in HTx patients. Here, we review current approaches and the state of research on novel biomarkers for the management of patients following heart transplantation. PMID- 26272189 TI - Anticancer drugs: A one-two punch for KRAS-driven cancer. PMID- 26272185 TI - Abnormalities of serotonergic neurotransmission in animal models of SUDEP. AB - Sudden unexpected death in epilepsy (SUDEP) is a devastating event, and both DBA/1 and DBA/2 mice have been shown to be relevant animal models for studying SUDEP. DBA mice exhibit seizure-induced respiratory arrest (S-IRA), leading to cardiac arrest and subsequent sudden death after generalized audiogenic seizures (AGSs). This sequence of terminal events is also observed in the majority of witnessed human SUDEP cases. Several pathophysiological mechanisms, including respiratory/cardiac dysfunction, have been proposed to contribute to human SUDEP. Several (but not all) selective serotonin (5-HT) reuptake inhibitors (SSRIs), including fluoxetine, can reversibly block S-IRA, and abnormal expression of 5-HT receptors is found in the brainstem of DBA mice. DBA mice, which do not initially show S-IRA, exhibit S-IRA after treatment with a nonselective 5-HT antagonist. These studies suggest that abnormalities of 5-HT neurotransmission are involved in the pathogenesis of S-IRA in DBA mice. Serotonergic (5-HT) transmission plays an important role in normal respiration, and DBA mice exhibiting S-IRA can be resuscitated using a rodent ventilator. It is important and interesting to know if fluoxetine blocks S-IRA in DBA mice by enhancing respiratory ventilation. To test this, the effects of breathing stimulants, doxapram, and 5,6,7,8 tetrahydropyrido[4,3-d]pyrimidine (PK-THPP) were compared with the effects of fluoxetine on S-IRA in DBA/1 mice. Although fluoxetine reduces the incidence of S IRA in DBA/1 mice, as reported previously, the same dose of fluoxetine fails to enhance baseline respiratory ventilation in the absence of AGSs. Doxapram and PK THPP augment the baseline ventilation in DBA/1 mice. However, these breathing stimulants are ineffective in preventing S-IRA in DBA/1 mice. These data suggest that fluoxetine blocks S-IRA in DBA/1 mice by cellular/molecular mechanisms other than enhancement of basal ventilation. Future research directions are also discussed. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic". PMID- 26272190 TI - Ageing: GRBbing longevity with both insulin signalling arms. PMID- 26272191 TI - Trends in breakthrough therapy designation. PMID- 26272192 TI - Market watch: Forecasting market share in the US pharmaceutical market. PMID- 26272193 TI - The potential therapeutic role of myeloid-derived suppressor cells in autoimmune arthritis. AB - OBJECTIVE: The aim of this review is to evaluate the roles of myeloid-derived suppressor cells (MDSC) in autoimmune arthritis. METHODS: The terms "myeloid derived suppressor cells," "regulatory T cell," "Th17 cell" and "autoimmune arthritis" were used for literature search from the PubMed. The publications about the characteristics of MDSC, the immunosuppression of MDSC, the role of MDSC in the regulation of Tregs and Th17 cells, and the potential clinical applications of MDSC against rheumatoid arthritis (RA) were identified, retrieved and reviewed. RESULTS: MDSC are defined as a heterogeneous population of pathologically activated immature and mature myeloid cells consisting of granulocytic and monocytic subsets. Published data showed that the role of MDSC in Tregs and Th17 cells expansion were inconsistent. Given their role in suppressing T-cell responses, MDSC have been tested for their capability of preventing RA. CONCLUSIONS: Although MDSC hold promise in the treatment of RA, their exact role in the expansion of Tregs and Th17 cells is unclear during RA. The definite effect of MDSC in RA therapy needs to be studied further. PMID- 26272195 TI - Pattern of online communication in teaching a blended oral surgery course. AB - AIM: To explore the factors that might affect the patterns of interaction amongst dental students that can be found in asynchronous online discussion fora. SUBJECTS AND METHODS: It is a qualitative study that involved the participation of 71 dental students (42 male and 29 female) who belong to one academic year. Students were participated in asynchronous online discussion fora as a part of a blended oral surgery course that involved both face-to-face lecture and an online learning environment using the Blackboard learning management system. Qualitative analysis of students' pattern of discussion was performed using Transcript Analysis Tool. RESULTS: The total number of postings was 410. Sixty-seven of 71 students participated in the discussion by writing posts, whereas all of the students had accessed all of the postings. A positive correlation between imposing vertical questions and the number of non-referential and referential statements was observed. Regarding horizontal questions, a positive correlation was observed with the number of referential statements, whilst there was a negative correlation with the number of non-referential statements. CONCLUSION: Asynchronous online discussion fora that are integrated as a part of a whole pedagogical practice may provide an opportunity for promoting learning, especially when consideration is given to the structure of problems, timely feedback by tutors and supportive strategies within the discussion threads. PMID- 26272196 TI - pi-pi interactions in carbon nanostructures. AB - pi-pi Interactions are the dominating supramolecular forces in systems like carbon nanostructures, which are inherently constituted by large conjugated pi systems. Their skilful use has allowed the construction of fascinating supramolecular ensembles, thus opening a new avenue in carbon chemistry. In this tutorial review, we provide a short introduction to carbon nanostructures, and show the basic concepts of pi-pi interactions involving fullerenes, carbon nanotubes, and graphene. PMID- 26272194 TI - A right ventricular diastolic impairment is common in systemic sclerosis and is associated with other target-organ damage. AB - OBJECTIVE: Heart involvement in systemic sclerosis (SSc) is a strong prognostic factor. Our aim was to examine left ventricle (LV) and right ventricle (RV) involvement. METHODS: We examined LV and RV, systolic and diastolic functions, using echocardiography and Tissue-Doppler echocardiography (TDE) indexes, in a cohort of 212 consecutive SSc patients seen during a 9-month period at 2 institutions (Paris, France and Los Angeles, USA). They were compared to 50 healthy controls. RESULTS: When compared to controls, SSc patients had consistently impaired RV indices that include reduced RV contractility (p < 0.001), larger right atrial area (p = 0.027) and overall RV diastolic dysfunction (25% of SSc patients versus 0% of controls; p < 0.001). Patients also exhibited alterations in LV contractility and diastolic function (p < 0.001 each). In multivariate analysis, RV contractility as expressed by the TDE S(T) parameter was associated with TDE LV contractility S(M) (p = 0.030), DLCO (p = 0.013) whereas RV diastolic impairment was associated with systolic pulmonary artery pressure (p = 0.015). A subgroup of 27 patients had proven pulmonary arterial hypertension (PAH); comparison between SSc-PAH versus SSc free of PAH patients revealed reduced LV diastolic function (transmitral E/A ratio, p = 0.045 and E(A) < 10 cm/s, p = 0.029), reduced overall RV contractility (21.5% versus 4.5%; p = 0.03) and reduced RV diastolic function (transtricuspid E/A ratio; p = 0.014 and 68% versus 29% with impaired function; p = 0.001). CONCLUSIONS: Our data show that RV is commonly affected in SSc with predominant impaired diastolic function. Several factors, including primary heart, lung vascular disease and pulmonary hypertension, contribute to such impairment. PMID- 26272197 TI - Enteral nutrition for maintaining remission in patients with quiescent Crohn's disease: current status and future perspectives. AB - PURPOSE: The value of enteral nutrition (EN) as maintenance therapy in patients with quiescent Crohn's disease (CD) has not been fully evaluated. The purpose of this study was to review the efficacy of EN for the maintenance of remission in patients with quiescent CD. METHODS: Seven prospective cohort studies evaluating the efficacy of EN for the maintenance of remission in quiescent CD were included. Three of the seven studies were randomized-controlled trials (RCTs). In all studies, patients used EN as a supplement or as a nocturnal tube feeding in addition to their normal food. RESULTS: One study compared the efficacy of elemental diet and polymeric diet. Elemental and polymeric diets were equally effective for the maintenance of clinical remission and for allowing tapering and cessation of steroid therapy. The other six studies compared the outcomes between patients treated with and without EN. The maintained clinical remission rate at 1 year was significantly higher in patients treated with EN in four of the six studies. Quantitative pooling of the studies was not feasible due to a small number of RCTs and a narrative account of the study characteristics. CONCLUSIONS: Our review suggests that EN is useful for the maintenance of remission in patients with quiescent CD. However, there are several limitations in the reviewed studies. There are few RCTs. Further, the sample size is small, and the duration of intervention and follow-up is short. Large and well-designed RCTs should be conducted to rigorously evaluate the efficacy of EN for maintaining remission. PMID- 26272198 TI - Dual-modal ablation treatment for refractory radiation proctitis. PMID- 26272199 TI - Patient- and procedure-related factors affecting proximal and distal detection rates for polyps and adenomas: results from 1603 screening colonoscopies. AB - BACKGROUND: Screening colonoscopy is less effective in reducing the incidence of proximal compared to distal colorectal cancer, presumably because of missed adenomas and advanced lesions during endoscopy. Thus, effectiveness and success of colorectal cancer (CRC) screening programs depend decisively on the quality of the endoscopic procedures. METHODS: A retrospective analysis of 1603 average risk screening colonoscopies to calculate and to identify determinants of separate detection rates for proximally and distally located polyps, adenomas, and advanced adenomas was performed. RESULTS: 56.1 % of 1603 individuals included were men, and the mean age was 60.2 +/- 10.2 years. Distal detection rates were markedly higher compared to proximal detection rates for polyps (40.9 vs. 23.8 %), adenomas (21.3 vs. 16.2 %), and advanced adenomas (4.0 vs. 2.0 %). A gradual increase in detection rates with increasing age was found for proximal and distal localization. Gender difference was also seen for polyps and adenomas, but not for advanced adenomas. In multivariate analysis, age <65.0 years and female gender were independently associated with a lower separate polyp detection rate (PDR) and adenoma detection rate (ADR). The use of propofol was the only procedure-related variable significantly associated with higher polyp detection rate. CONCLUSION: Since age and gender affect detection rates of proximally and distally located polyps and adenomas, the requirement of a specific gender related limit in total detection rates may be insufficient as a quality indicator for screening colonoscopies. PMID- 26272200 TI - Performance characteristics of six automated 25-hydroxyvitamin D assays: Mind your 3s and 2s. AB - BACKGROUND: Measurement of 25(OH)D has evolved rapidly, with an increased number of high-throughput automated immunoassays becoming available in recent years. The aim of this study was to fully evaluate six commercially available automated 25(OH)D immunoassays, including 2 newly available (Beckman Coulter) and one recalibrated (Siemens) assay. Comparisons were made to specifically identify the effect of the absence or presence of 25(OH)D2 on these assays. DESIGN AND METHODS: Access2 and UniCel DxI 800 (Beckman Coulter), ARCHITECT i2000SR (Abbott Diagnostics), ADVIA Centaur XP (Siemens), Liaison XL (DiaSorin) and MODULAR E170 (Roche Diagnostics) assays were assessed for accuracy, imprecision, interference, limit of blank, and linearity. All were compared to an in-house LC-MS/MS method (traceable to NIST SRM 972) using Passing-Bablok regression and Bland-Altman bias plots. Method comparisons used residual serum samples with both endogenous 25(OH)D2 and 25(OH)D3 (n=50) or 25(OH)D3 only (n=86). Comparisons with all 136 samples were intended to simulate real-world laboratory testing. RESULTS: The majority of assays under-recovered 25(OH)D in comparison to LC-MS/MS, with three of six immunoassays affected by the presence of 25(OH)D2. Imprecision was greatest at 25(OH)D concentrations near the decision limits used to assess deficiency. Only two of six immunoassays would meet the recommended bias criteria of <5%. CONCLUSIONS: Although standardization efforts continue, these differences in performance remain a concern. Clinicians should be aware when comparing results among assays and using them to determine adequacy of 25(OH)D stores in various patient populations. PMID- 26272202 TI - Treatment of bladder pain syndrome and interstitial cystitis: a systematic review. AB - INTRODUCTION AND HYPOTHESIS: Bladder pain syndrome/interstitial cystitis (BPS/IC) has various treatments; however, no standardized treatment has been established. The aim was to analyze different types of treatment of BPS/IC and their effectiveness. METHODS: A literature review with a search strategy for articles related to BPS/IC published between 1990 and 2014 was conducted on MEDLINE, PUBMED, and SCOPUS. Only randomized controlled trials in women were included in the meta-analysis, while other experimental studies were used as bases for a systematic review of the topic. Clinical trial quality was defined according to the Jadad scale. RESULTS: Of 356 articles, 13 were included in the analysis. The intervention methods were as follows: instillation of hyaluronic acid, botulinum toxin A, intravesical lidocaine, hyperbaric chamber, massage, physiotherapy, phosphate-buffered saline, piroxicam in combination with doxepin, and others. We did not find any treatment with at least two randomized controlled trials for meta-analysis. Among the assessment tools for symptoms of BPS/IC, the most frequently used were the visual analogue scale, voiding record, and the O'Leary Sant questionnaire. CONCLUSION: Existing studies were not able to define the best approach for the treatment of BPS/IC. The lack of standardized treatment may be related to the diversity of interventions used; therefore, further studies with better methodological quality are needed. PMID- 26272203 TI - Predicting chromatin organization using histone marks. AB - Genome-wide mapping of three dimensional chromatin organization is an important yet technically challenging task. To aid experimental effort and to understand the determinants of long-range chromatin interactions, we have developed a computational model integrating Hi-C and histone mark ChIP-seq data to predict two important features of chromatin organization: chromatin interaction hubs and topologically associated domain (TAD) boundaries. Our model accurately and robustly predicts these features across datasets and cell types. Cell-type specific histone mark information is required for prediction of chromatin interaction hubs but not for TAD boundaries. Our predictions provide a useful guide for the exploration of chromatin organization. PMID- 26272204 TI - Comparative analysis of anti-viral transcriptomics reveals novel effects of influenza immune antagonism. AB - BACKGROUND: Comparative analysis of genome-wide expression profiles are increasingly being used to study virus-specific host interactions. In order to gain mechanistic insights, gene expression profiles can be combined with information on DNA-binding sites of transcription factors to detect transcription factor activity (by analysis of target gene sets) during viral infections. Here, we apply this approach to study mechanisms of immune antagonism elicited by Influenza A virus (New Caledonia/20/1999) by comparing the transcriptional response with the non-pathogenic Newcastle disease virus (NDV), which lacks human immune antagonism. RESULTS: Existing gene set approaches do not quantify activity in a way that can be statistically compared between responses. We thus developed a new method for Bayesian Estimation of Transcription factor Activity (BETA) that allows for such quantification and comparative analysis across multiple responses. BETA predicted decreased ISGF3 activity during influenza A infection of human dendritic cells (reflected in lower expression of Interferon Stimulated Genes, ISGs). This prediction was confirmed through a combination of mathematical modeling and experiments at different multiplicities of infection to show that ISGs were specifically blocked in infected cells. Suppression of the transcription factor SATB1 was also predicted as a novel effect of influenza mediated immune antagonism, and validated experimentally. CONCLUSIONS: Comparative analysis of genome-wide transcriptional profiles can reveal new effects of viral immune antagonism. We have developed a computational framework (BETA) that enables quantitative comparative analysis of transcription factor activities. This method will aid future studies to identify mechanistic differences in the host-pathogen interactions. Application of BETA to genome-wide transcriptional profiling data from human DCs identified SATB1 as a novel effect of influenza antagonism. PMID- 26272206 TI - Comparison of the nutrient content of children's menu items at US restaurant chains, 2010-2014. AB - OBJECTIVE: To determine changes in the nutritional content of children's menu items at U.S. restaurant chains between 2010 and 2014. METHODS: The sample consisted of 13 sit down and 16 fast-food restaurant chains ranked within the top 50 US chains in 2009. Nutritional information was accessed in June-July 2010 and 2014. Descriptive statistics were calculated for nutrient content of main dishes and side dishes, as well as for those items that were added, removed, or unchanged during the study period. RESULTS: Nutrient content of main dishes did not change significantly between 2010 and 2014. Approximately one-third of main dishes at fast-food restaurant chains and half of main dishes at sit down restaurant chains exceeded the 2010 Dietary Guidelines for Americans recommended levels for sodium, fat, and saturated fat in 2014. Improvements in nutrient content were observed for side dishes. At sit down restaurant chains, added side dishes contained over 50% less calories, fat, saturated fat, and sodium, and were more likely to contain fruits/vegetables compared to removed sides (p < 0.05 for all comparisons). Added side dishes at fast-food restaurant chains contained less saturated fat (p < 0.05). CONCLUSIONS: The majority of menu items, especially main dishes, available to children still contain high amounts of calories, fat, saturated fat, and sodium. Efforts must be made by the restaurant industry and policy makers to improve the nutritional content of children's menu items at restaurant chains to align with the Dietary Guidelines for Americans. Additional efforts are necessary to help parents and children make informed choices when ordering at restaurant chains. PMID- 26272208 TI - A finger photoplethysmography waveform during the valsalva maneuver detects changes in left heart filling pressure after hemodialysis. AB - BACKGROUND: A noninvasive system for determining left ventricular (LV) filling pressure may help to improve personalized fluid removal goals in hemodialysis patients. We previously showed that the change in photoplethysmography (PPG) pulse amplitude measured by finger PPG during a Valsalva maneuver correlates with invasively measured left ventricular end-diastolic pressure (LVEDP). This key PPG change, the ratio of finger PPG pulse amplitude at end-Valsalva to baseline, is known as the Pulse Amplitude Ratio, PAR. The objective of this study was to determine how PAR changes after fluid removal in hemodialysis. METHODS: We tested subjects with end-stage renal disease, before and after hemodialysis. Each subject performed a Valsalva maneuver with an effort of 20 mmHg for 10 s, guided by the device display. Finger PPG was recorded continuously before and during the maneuver. PAR was calculated automatically. RESULTS: Twenty-seven subjects (21 Males) ages 25-75 years were tested. Access sites were AV-fistulas of the arm predominantly. Weight decreased from 99.7 +/- 36.9 kg to 97.0 +/- 6.0 kg (p < 0.0003) with an average fluid removal of 3.07 +/- 1.08 l. Correspondingly, PAR decreased from 0.74 +/- 0.24 to 0.62 +/- 0.23 (p = 0.003). The change in PAR was correlated with baseline PAR (r = 0.48, p = 0.01). CONCLUSION: An index of left heart filling pressure obtained noninvasively using finger photoplethysmography during the Valsalva maneuver is sensitive enough to detect reductions in filling pressure after fluid removal with hemodialysis. Further studies are warranted to determine if this method can be used to guide fluid removal during hemodialysis. PMID- 26272209 TI - Cytologic Diagnosis of Heterobilharzia americana Infection in a Liver Aspirate From a Dog. AB - Heterobilharzia americanais a trematode of the Schistosomatidae family that infects dogs, raccoons, and other mammals as definitive hosts. This parasite is considered endemic in the southern Atlantic and Gulf coasts; however, only a few cases are reported. A 7-year-old dog from Louisiana was referred for persistent hypercalcemia, hyperglobulinemia, and weight loss. Abdominal ultrasound revealed diffuse hyperechogenicity of the liver with several hyperechoic nodules of varying size. Cytologic examination of fine-needle aspirates of the liver revealed few ovoid to round basophilic thin-walled eggshell fragments and rare ciliated miracidia.H. americanaeggs were identified on fecal sedimentation. PMID- 26272207 TI - Erratum to: Study protocol: differential effects of diet and physical activity based interventions in pregnancy on maternal and fetal outcomes: individual patient data (IPD) meta-analysis and health economic evaluation. PMID- 26272210 TI - Competition between Halogen Bonding and pi-Hole Interactions Involving Various Donors: The Role of Dispersion Effects. AB - In this study several sigma- and pi-hole complexes between IF and pnicogen ZO2 F (Z=P, As), chalcogen ChO3 (Ch=S, Se) and tetrel TrOF2 (Tr=Si, Ge) -bearing compounds were optimized at the RI-MP2/def2-TZVPD level of theory. All complexes were characterized as minima by frequency analysis calculations. In addition, a comparative CCSD(T) and DFT (with and without dispersion correction) study using the BP86, B3LYP and M06-2X method was done in order to analyze the role of dispersion effects in the sigma-/pi-hole binding. Finally the Bader's AIM analysis of several complexes was performed to further characterize the interactions discussed herein. PMID- 26272211 TI - Examining the Effects of Parental Influence on Adolescent Smoking Behaviors: A Multilevel Analysis of the Global School-Based Student Health Survey (2003-2011). AB - INTRODUCTION: Based on a large cross-national dataset, we investigated the role of parental smoking (a risk factor) and parental supervision (a protective factor) on the frequency of smoking by youths in resource-poor countries. In addition, we tested for cross-level interactions between these two predictors and national wealth on the outcome variable. METHODS: Pooled cross-sectional data from the Global School-based Student Health Survey (2003-2011) were analyzed, which consists of 58956 students in 31 countries. Hierarchical linear models were estimated to examine the associations between the two parental influence variables and adolescent smoking. RESULTS: Among the control variables, age, gender (male), the experience of being bullied, frequency of getting into physical fights, truancy, and anxiety were significantly related to higher frequency of smoking. With respect to the main predictors, both at the individual level, parental supervision was negatively associated with adolescent smoking, while parental smoking was positively related to it. Two cross-level interaction terms were also observed. National wealth (GDP per capita) significantly moderated, that is, increased, these effects of parental influence on how often the adolescents smoked. CONCLUSIONS: We provided new evidence on the factors related to adolescent smoking in low-income countries, a topic that has received very little attention. We showed that the associations between parental influences and adolescent smoking behaviors are not constant but vary according to the level of economic development. Future research should incorporate this comparative dimension in elaborating and specifying the conditions under which parental influences and other predictors differentially affect adolescent smoking. IMPLICATIONS: Prior research on adolescent smoking focused on developed countries. Based on the secondary analysis of the Global School-based Student Health Survey (2003-2011), this study examines the associations between parental influence (parental smoking and parental supervision) on the frequency of youth smoking behaviors in resource-poor countries. We show that parental smoking is positively related to adolescent smoking, while parental supervision is negatively related to it. We also find that these two associations vary according to national wealth: both effects are stronger in a country with higher per capita GDP. PMID- 26272212 TI - Acute Exposure to Electronic and Combustible Cigarette Aerosols: Effects in an Animal Model and in Human Alveolar Cells. AB - BACKGROUND: Smoking electronic cigarettes (ECIG) is promoted as a safer alternative to smoking combustible cigarettes. This study investigates the effects of ECIG aerosol and cigarette smoke (CS) in an animal model and in human alveolar cell cultures (A549). METHODS: Mice were divided into Control, ECIG, and CS. Animals were exposed for 6h/d to either lab air, ECIG or CS, for of 3 days. Total particulate matter exposure for the ECIG was set at higher levels compared to CS. Lung injury was determined by: (1) measurement of wet-to-dry ratio; (2) albumin concentration in the bronchoalveolar lavage fluid; (3) transcriptional expression of inflammatory mediators IL-1beta, IL-6, TNF-alpha; (4) oxidative stress; (5) assessment of cell death; and (6) lung histopathology. Human alveolar cell cultures were treated with various concentrations of ECIG and CS aerosol extracts and the effects on cell proliferation were evaluated. RESULTS: Wet-to dry ratio was higher in CS when compared to ECIG. Albumin leak in bronchoalveolar lavage fluid was evident in CS but not in ECIG. ECIG exposure was only associated with a significant increase in IL-1beta. In contrast, CS exposure resulted in significant increases in IL-1beta, IL-6, TNF-alpha expression, and oxidative stress. TUNEL staining demonstrated significant cell death in CS but not in ECIG. At the cellular level, ECIG and CS extracts reduced cell proliferation, however, CS exhibited effects at lower concentrations. CONCLUSION: Despite higher exposure conditions, ECIG exhibited less toxic effects on lungs of experimental animals and on A549 cell cultures when compared to CS. PMID- 26272213 TI - Association between plasma fluorescent oxidation products and erectile dysfunction: A prospective study. AB - BACKGROUND: Existing epidemiological studies of the association between oxidative stress and erectile dysfunction (ED) are sparse and inconclusive, which is likely due to cross-sectional design and small sample size. Therefore, we investigated the association between biomarkers of oxidative stress and ED in prospective setting among a relatively large sample size of men. METHODS: We conducted the prospective study among 917 men ages between 47 and 80 years at the time of blood draw, which is a part of nested prospective case-control study of prostate cancer in the Health Professionals Follow-up Study. Plasma fluorescent oxidation products (FlOPs), a global biomarker for oxidative stress, were measured at three excitation/emission wavelengths (360/420 nm named as FlOP_360; 320/420 nm named as FlOP_320 and 400/475 nm named as FlOP_400). RESULTS: Approximately 35% of men developed ED during follow-up. We did not find an independent association between FlOP_360, FlOP_320, FlOP_400 and risk of ED in the multivariable adjusted model (Tertile 3 vs. tertile 1: odds ratio [OR] = 0.90, 95% confidence interval [CI] = 0.61-1.34, P(trend) = 0.54 for FlOP_360; OR = 0.73, 95% CI = 0.49-1.07, P(trend) = 0.27 for FlOP_320; and OR = 0.98, 95% CI = 0.66-1.45, P(trend) = 0.72 for FlOP_400). Further analysis of the association between FlOPs and ED in the fasting samples or controls only (free of prostate cancer incidence) did not change the results appreciably. CONCLUSIONS: Plasma FlOPs were not associated with the risk of ED, suggesting oxidative stress may not be an independent risk factor for ED. PMID- 26272214 TI - Anti-lung Cancer Effects of Polyphyllin VI and VII Potentially Correlate with Apoptosis In Vitro and In Vivo. AB - Polyphyllin VI (PVI) and polyphyllin VII (PVII) derived from Paris polyphylla possess anti-cancer activities. However, the mechanisms for the anti-lung cancer effects of PVI and PVII remain poorly understood. In this study, PVI and PVII exhibited inhibitory effects on the proliferation of A549 and NCI-H1299 cells. PVI and PVII induced G2/M cell cycle arrest and triggered apoptosis. PVI and PVII upregulated the tumor suppressor protein p53 and downregulated cyclin B1. The two treatments significantly increased the expression levels of death receptor 3, death receptor 5, Fas, cleaved PARP, and cleaved caspase-3. Furthermore, PVI and PVII significantly inhibited the growth of A549 cells in vivo. The tumor inhibitory rates of PVI were 25.74%, 34.62%, and 40.43% at 2, 3, and 4 mg/kg, respectively, and those of PVII were 25.63%, 41.71%, and 40.41% at 1, 2, and 3 mg/kg, respectively. Finally, PVI and PVII regulated the expression of proteins related to the apoptotic pathway in A549 xenografts. In summary, PVI and PVII exhibited strong inhibitory effects on lung cancer cell growth in vitro and in vivo by inducing G2/M cell cycle arrest and triggering apoptosis. PMID- 26272215 TI - Poly(U) RNA-templated synthesis of AppA. AB - Simple nucleotide templating activities are of interest as potential primordial reactions. Here we describe the acceleration of 5'-5' AppA synthesis by 3'-5' poly(U) under normal solution conditions. This reaction is apparently templated via complementary U:A base-pairing, despite the involvement of two different RNA backbones, because poly(U), unlike other polymers, significantly stimulates AppA synthesis. These interactions occur in moderate (K(+)) and (Mg(2+)) and are temperature sensitive, being more efficient at 10 degrees C than at 4 degrees C, but absent at 20 degrees C. The reaction is only slightly pH sensitive, despite potentially relevant substrate pKa's. Kinetic data explicitly support production of AppA by interaction of stacked 2MeImpA and pA nucleotides paired with a single molecule of U template. At a lower rate, AppA can also be produced by a chemical reaction between 2MeImpA and pA, without participation of poly(U). Molecular modeling suggests that 5'-5' joining between stacked or concurrently paired A's can occur without major departures from normal U-A helical coordinates. So, coenzyme-like 5'-5' purine dinucleotides might be readily synthesized from 3'-5' RNAs with complementary sequences. PMID- 26272216 TI - DC-SIGN-expressing macrophages trigger activation of mannosylated IgM B-cell receptor in follicular lymphoma. AB - Follicular lymphoma (FL) results from the accumulation of malignant germinal center (GC) B cells leading to the development of an indolent and largely incurable disease. FL cells remain highly dependent on B-cell receptor (BCR) signaling and on a specific cell microenvironment, including T cells, macrophages, and stromal cells. Importantly, FL BCR is characterized by a selective pressure to retain surface immunoglobulin M (IgM) BCR despite an active class-switch recombination process, and by the introduction, in BCR variable regions, of N-glycosylation acceptor sites harboring unusual high-mannose oligosaccharides. However, the relevance of these 2 FL BCR features for lymphomagenesis remains unclear. In this study, we demonstrated that IgM(+) FL B cells activated a stronger BCR signaling network than IgG(+) FL B cells and normal GC B cells. BCR expression level and phosphatase activity could both contribute to such heterogeneity. Moreover, we underlined that a subset of IgM(+) FL samples, displaying highly mannosylated BCR, efficiently bound dendritic cell specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), which could in turn trigger delayed but long-lasting BCR aggregation and activation. Interestingly, DC-SIGN was found within the FL cell niche in situ. Finally, M2 macrophages induced a DC-SIGN-dependent adhesion of highly mannosylated IgM(+) FL B cells and triggered BCR-associated kinase activation. Interestingly, pharmacologic BCR inhibitors abolished such crosstalk between macrophages and FL B cells. Altogether, our data support an important role for DC-SIGN-expressing infiltrating cells in the biology of FL and suggest that they could represent interesting therapeutic targets. PMID- 26272217 TI - How I treat high-risk myeloma. AB - The treatment of patients with myeloma has dramatically changed over the past decade due in part to the development of new agents and myeloma-specific targets. Despite these advancements, a group for whom the long-term benefit remains less clear are patients with genetically or clinically defined high-risk myeloma. In order to successfully treat these patients, it is important to first identify these patients, treat them with aggressive combination therapy, and employ the use of aggressive long-term maintenance therapy. Future directions include the use of new immune-based treatments (antibodies or cellular-based therapies) as well as target-driven approaches. Until these treatment approaches are better defined, this review will provide a potential treatment approach for standard- and high-risk myeloma that can be followed using agents and strategies that are currently available with the goal of improving progression-free and overall survival for these patients today. PMID- 26272218 TI - Folic acid supplementation for pregnant women and those planning pregnancy: 2015 update. AB - During the last decade critical new information has been published pertaining to folic acid supplementation in the prevention of neural tube defects (NTDs) and other folic acid-sensitive congenital malformations. These new data have important implications for women, their families, and health care professionals. We performed a review looking for the optimal dosage of folic acid that should be given to women of reproductive age who are planning or not avoiding conception to propose updated guidelines and thus help health care providers and patients. In addition to fortification of dietary staples with folic acid, women of reproductive age should supplement before conception with 0.4-1.0 mg of folic acid daily as part of their multivitamins. In the United States all enriched rice is also fortified with folic acid at 0.7 mg per pound of raw rice. However, this is not the case in many countries, and it has been estimated that only 1% of industrially milled rice is fortified with folic acid. In countries where rice is the main staple (eg, China), this does not allow effective folate fortification. Whereas the incidence of NTDs is around 1/1000 in the United States, it is 3- to 5-fold higher in Northern China and 3-fold higher in India. A recent population based US study estimated that the reduction in NTD rates by folic acid is more modest than previously predicted. The potential of NTD prevention by folic acid is underutilized due to low adherence with folic acid supplementation, and calls for revising the policy of supplementation have been raised. We identified groups of women of reproductive age who may benefit from higher daily doses of folic acid, and this should be considered in current practice. These include women who have had previous pregnancies with NTDs, those who did not plan their pregnancy and hence did not supplement, and women with low intake or impaired adherence to daily folic acid supplementation. In addition, women with known genetic variations in the folate metabolic cycle, those exposed to medications with antifolate effects, smokers, diabetics, and the obese may benefit from higher doses of folic acid daily during the first trimester. PMID- 26272219 TI - Interaction of milk proteins and Binder of Sperm (BSP) proteins from boar, stallion and ram semen. AB - BACKGROUND: Mammalian semen contains a family of closely related proteins known as Binder of SPerm (BSP proteins) that are added to sperm at ejaculation. BSP proteins extract lipids from the sperm membrane thereby extensively modifying its composition. These changes can ultimately be detrimental to sperm storage. We have demonstrated that bovine BSP proteins interact with major milk proteins and proposed that this interaction could be the basis of sperm protection by milk extenders. In the present study, we investigated if homologous BSP proteins present in boar, stallion and ram seminal plasma display a similar affinity for the milk proteins in order to assess whether the mechanism of sperm protection by milk for these species could be general. METHODS: Skim milk was incubated with seminal plasma proteins (boar, stallion and ram), chromatographed on a Sepharose CL-4B column and protein fractions were analyzed by immunoblotting. RESULTS: Boar, stallion and ram BSP proteins displayed affinity for a milk protein fraction (F1) mainly composed of alpha-lactalbumin, beta-lactoglobulin, and kappa casein. They also had affinity for another milk protein fraction (F2) composed mostly of casein micelles. However, stallion BSP showed higher affinity for the fraction (F1). CONCLUSIONS: These results further extend our view that the association of BSP proteins with milk proteins could be a general feature of the mechanism of mammalian sperm protection by milk to prevent detrimental effect of prolonged exposure of sperm to seminal plasma. PMID- 26272221 TI - Tocopherols in the Prevention and Treatment of Atherosclerosis and Related Cardiovascular Disease. AB - Oxidants/antioxidants play an important role in cellular homeostasis. The human body has endogenous molecules that work as antioxidants, such as glutathione, superoxide dismutase, peroxidases, and catalase. Exogenous substances in the diet, such as beta-carotene, ascorbate, and vitamin E, are vital antioxidants. Of these, vitamin E is likely the most important antioxidant in the human diet, and many studies have been performed to elucidate its role in health and disease. Vitamin E is a family of several compounds, of which alpha-tocopherol is the most widely known analog. alpha-Tocopherol exhibits antioxidative property in vitro and inhibits oxidation of low-density lipoprotein cholesterol. In addition, alpha tocopherol shows anti-inflammatory activity and modulates expression of proteins involved in the uptake, transport, and degradation of atherogenic lipids. Though alpha-tocopherol exhibits important antioxidant, anti-inflammatory, and antiatherogenic features in vitro, alpha-tocopherol supplements have failed to consistently reduce atherosclerosis-related events in human trials. The conflicting results have led to reconsideration of the importance previously given to alpha-tocopherol and led to interest in other members of vitamin E family, especially gamma-tocopherol, which exerts a much more potent antioxidant, anti-inflammatory, and cardioprotective effect than alpha-tocopherol. This reconsideration has been backed by solid laboratory and clinical research. We suggest that the absence of gamma-tocopherol in traditional preparations may be one reason for the lack of consistent salutary effects of vitamin E preparations in clinical trials. This review summarizes our current understanding of tocopherols as antioxidant molecules and emerging evidence of an important role of gamma-tocopherol in the pathophysiology of atherosclerosis-related cardiovascular disease. PMID- 26272222 TI - Why most oral insulin formulations do not reach clinical trials. AB - Oral insulin able to induce an efficient antihyperglycemic effect either to replace or complement diabetes mellitus therapy is the major goal of health providers, governments and diabetic patients. Oral therapy is associated not only with the desire to exclude needles from the daily routine of diabetic patient but also with the physiological provision of insulin they would get. Despite numerous efforts over the past few decades to develop insulin delivery systems, there is still no commercially available oral insulin. The reasons why the formulations developed to administer insulin orally fail to reach clinical trials are critically discussed in this review. The principal features of nanoformulations used so far are also addressed as well as the undergoing clinical trials. PMID- 26272220 TI - Components and characteristics of the dopamine reward utility signal. AB - Rewards are defined by their behavioral functions in learning (positive reinforcement), approach behavior, economic choices, and emotions. Dopamine neurons respond to rewards with two components, similar to higher order sensory and cognitive neurons. The initial, rapid, unselective dopamine detection component reports all salient environmental events irrespective of their reward association. It is highly sensitive to factors related to reward and thus detects a maximal number of potential rewards. It also senses aversive stimuli but reports their physical impact rather than their aversiveness. The second response component processes reward value accurately and starts early enough to prevent confusion with unrewarded stimuli and objects. It codes reward value as a numeric, quantitative utility prediction error, consistent with formal concepts of economic decision theory. Thus, the dopamine reward signal is fast, highly sensitive and appropriate for driving and updating economic decisions. PMID- 26272223 TI - The effect of Duschinsky rotation on charge transport properties of molecular junctions in the sequential tunneling regime. AB - We present here a systematic theoretical study on the effect of Duschinsky rotation on charge transport properties of molecular junctions in the sequential tunneling regime. In the simulations we assume that only two electronic charging states each coupled to a two dimensional vibrational potential energy surface (PES) are involved in the transport process. The Duschinsky rotation effect is accounted by varying the rotational angle between the two sets of displaced PESs. Both harmonic potential and anharmonic Morse potential have been considered for the cases of the intermediate to strong electron-vibration couplings. Our calculations show that the inclusion of the Duschinsky rotation effect can significantly change the charge transport properties of a molecular junction. Such an effect makes the otherwise symmetric Coulomb diamond become asymmetric in harmonic potentials. Depending on the angle of the rotation, the low bias current could be significantly suppressed or enhanced. This effect is particularly prominent in the Franck-Condon (FC) blockade regime where the electron-vibration coupling is strong. These changes are caused by the variation of the FC factors which are closely related to the rotational angle between the two sets of PESs involved in the charge transport process. For a molecular junction with Morse potentials, the changes caused by Duschinsky rotation are much more complicated. Both the amplitude and shape of the Coulomb diamond are closely dependent on the rotational angle in the whole range from 0 to 2pi. One interesting result is that with a rotation angle of pi (and also pi/2 for certain cases) symmetric Coulomb diamonds can even be formed from the intrinsically asymmetric Morse potential. These results could be important for the interpretation of experimental observations. PMID- 26272224 TI - The role of natural disaster in individual and relational adjustment in Sri Lankan mothers following the 2004 tsunami. AB - The purpose of this study is to examine the associations between maternal mental health distress symptoms, including depression and post-traumatic stress disorder, the extent to which the presence of a child's disaster-related physical health problem(s) have interfered with daily functioning, and family cohesion over time among Sri Lankan mothers who survived the tsunami on 26 December 2004. Study variables were measured using a self-report questionnaire administered approximately four months after the event and three years later in summer 2008. Univariate, bivariate, and multivariate analyses were conducted. Path analysis was employed to assess the relationships between the key variables over time and the correlations in the study variables at each time point. Among other findings, the results of the path analysis indicated that post-traumatic stress symptom distress four months after the disaster significantly predicted variance in family cohesion three years later. Clinical and empirical research implications are presented and discussed. PMID- 26272225 TI - The human oral metaproteome reveals potential biomarkers for caries disease. AB - Tooth decay is considered the most prevalent human disease worldwide. We present the first metaproteomic study of the oral biofilm, using different mass spectrometry approaches that have allowed us to quantify individual peptides in healthy and caries-bearing individuals. A total of 7771 bacterial and 853 human proteins were identified in 17 individuals, which provide the first available protein repertoire of human dental plaque. Actinomyces and Coryneybacterium represent a large proportion of the protein activity followed by Rothia and Streptococcus. Those four genera account for 60-90% of total diversity. Healthy individuals appeared to have significantly higher amounts of L-lactate dehydrogenase and the arginine deiminase system, both implicated in pH buffering. Other proteins found to be at significantly higher levels in healthy individuals were involved in exopolysaccharide synthesis, iron metabolism and immune response. We applied multivariate analysis in order to find the minimum set of proteins that better allows discrimination of healthy and caries-affected dental plaque samples, detecting seven bacterial and five human protein functions that allow determining the health status of the studied individuals with an estimated specificity and sensitivity over 96%. We propose that future validation of these potential biomarkers in larger sample size studies may serve to develop diagnostic tests of caries risk that could be used in tooth decay prevention. PMID- 26272226 TI - Far-Red Emitting Fluorescent Dyes for Optical Nanoscopy: Fluorinated Silicon Rhodamines (SiRF Dyes) and Phosphorylated Oxazines. AB - Far-red emitting fluorescent dyes for optical microscopy, stimulated emission depletion (STED), and ground-state depletion (GSDIM) super-resolution microscopy are presented. Fluorinated silicon-rhodamines (SiRF dyes) and phosphorylated oxazines have absorption and emission maxima at about lambda~660 and 680 nm, respectively, possess high photostability, and large fluorescence quantum yields in water. A high-yielding synthetic path to introduce three aromatic fluorine atoms and unconventional conjugation/solubilization spacers into the scaffold of a silicon-rhodamine is described. The bathochromic shift in SiRF dyes is achieved without additional fused rings or double bonds. As a result, the molecular size and molecular mass stay quite small (<600 Da). The use of the lambda=800 nm STED beam instead of the commonly used one at lambda=750-775 nm provides excellent imaging performance and suppresses re-excitation of SiRF and the oxazine dyes. The photophysical properties and immunofluorescence imaging performance of these new far-red emitting dyes (photobleaching, optical resolution, and switch-off behavior) are discussed in detail and compared with those of some well established fluorophores with similar spectral properties. PMID- 26272227 TI - The cost-utility of dabigatran etexilate compared with warfarin in treatment and extended anticoagulation of acute VTE in the UK. AB - The relative efficacy and safety of dabigatran etexilate and warfarin have been evaluated in two head-to-head, phase III, treatment of acute venous thromboembolism (VTE) trials, and one extended prophylaxis trial, in patients with high risk of recurrent VTE. Dabigatran etexilate demonstrated similar efficacy to warfarin, and was associated with a reduced risk of major or clinically relevant bleeds. Based on results of these trials, and real-life disease prognosis following discontinuation of anticoagulation treatment, we evaluated the cost-utility of dabigatran etexilate compared with warfarin in six months anticoagulation, and in extended, up to 24 months anticoagulation, in patients with acute VTE, acute deep-vein thrombosis (DVT) or acute, symptomatic, pulmonary embolism (PE). Costs were analysed from the perspective of the National Health Services (NHS) and Public Social Services (PSS) in England and Wales. Outcomes were quantified in quality-adjusted life years (QALY). The estimated incremental, lifetime cost/QALY gain following acute, symptomatic VTE (DVT or PE) was L1,252/QALY when dabigatran etexilate or warfarin were administered for up to six months treatment. In treatment of acute, symptomatic PE and in DVT respective ratios were L1,767/QALY and L1,075/QALY. In extended, up to 24 months anticoagulation, dabigatran etexilate projected costs/QALY of L8,242/QALY, when compared with warfarin. Results obtained herein were robust across a number of sensitivity analyses and suggest dabigatran etexilate to be a cost-effective alternative to current standard of care when evaluated in six months treatment and in extended anticoagulation following acute VTE (DVT and/or PE). PMID- 26272228 TI - Understanding nurses' and physicians' fear of repercussions for reporting errors: clinician characteristics, organization demographics, or leadership factors? AB - BACKGROUND: Identifying and understanding factors influencing fear of repercussions for reporting and discussing medical errors in nurses and physicians remains an important area of inquiry. Work is needed to disentangle the role of clinician characteristics from those of the organization-level and unit-level safety environments in which these clinicians work and learn, as well as probing the differing reporting behaviours of nurses and physicians. This study examines the influence of clinician demographics (age, gender, and tenure), organization demographics (teaching status, location of care, and province) and leadership factors (organization and unit leadership support for safety) on fear of repercussions, and does so for nurses and physicians separately. METHODS: A cross-sectional analysis of 2319 nurse and 386 physician responders from three Canadian provinces to the Modified Stanford patient safety climate survey (MSI 06). Data were analyzed using exploratory factor analysis, multiple linear regression, and hierarchical linear regression. RESULTS: Age, gender, tenure, teaching status, and province were not significantly associated with fear of repercussions for nurses or physicians. Mental health nurses had poorer fear responses than their peers outside of these areas, as did community physicians. Strong organization and unit leadership support for safety explained the most variance in fear for both nurses and physicians. CONCLUSIONS: The absence of associations between several plausible factors including age, tenure and teaching status suggests that fear is a complex construct requiring more study. Substantially differing fear responses across locations of care indicate areas where interventions may be needed. In addition, since factors affecting fear of repercussions appear to be different for nurses and physicians, tailoring patient safety initiatives to each group may, in some instances, be fruitful. Although further investigation is needed to examine these and other factors in detail, supportive safety leadership appears to be central to reducing fear of reporting errors for both nurses and physicians. PMID- 26272229 TI - Glycaemic control is a predictor of infection-related hospitalization on haemodialysis patients: Miyazaki Dialysis Cohort study (MID study). AB - AIM: Although infection is the second leading cause of death in maintenance haemodialysis patients, the effects of glycaemic control on infection in diabetic haemodialysis patients have not yet been examined in detail. We examined the relationship between diabetes or glycemic control and infection-related hospitalization (IRH) in haemodialysis patients. METHODS: Patients receiving maintenance haemodialysis (n = 1551, 493 diabetic patients) were enrolled in this prospective cohort study in December 2009 and followed-up for 3 years. IRH during the follow-up period was abstracted from medical records. Kaplan-Meier and Cox regression analyses were used to investigate the relationship between diabetes or glycaemic control and IRH. RESULTS: The Kaplan-Meier analysis revealed that the risk of IRH was significantly higher in haemodialysis patients with diabetes, particularly in those with poorly controlled HbA1c levels (HbA1c >= 7.0%), than in haemodialysis patients without diabetes. When patients with >=HbA1c 7.0% were divided into two groups using a median value of HbA1c, the risk of IRH was significantly higher in those with the poorest glycaemic control (HbA1c >= 7.4%), an older age, or lower albumin levels. The multivariable-adjusted hazard ratio for the risk of IRH was not higher in the second criteria of HbA1c (HbA1c 7.0 7.3%), but was significantly higher in the group with the poorest glycaemic control (HbA1c >= 7.4%) than in those in the good control criterion (HbA1c < 7.0%). CONCLUSIONS: Although diabetes is a risk factor for IRH among maintenance haemodialysis patients, the relationship between glycaemic control and the risk of infection is not linear. Therefore, the risk of infection may increase in a manner that is dependent on the glycaemic control threshold. PMID- 26272231 TI - Ratiometric fluorescent sensing of pH values in living cells by dual-fluorophore labeled i-motif nanoprobes. AB - We designed a new ratiometric fluorescent nanoprobe for sensing pH values in living cells. Briefly, the nanoprobe consists of a gold nanoparticle (AuNP), short single-stranded oligonucleotides, and dual-fluorophore-labeled i-motif sequences. The short oligonucleotides are designed to bind with the i-motif sequences and immobilized on the AuNP surface via Au-S bond. At neutral pH, the dual fluorophores are separated, resulting in very low fluorescence resonance energy transfer (FRET) efficiency. At acidic pH, the i-motif strands fold into a quadruplex structure and leave the AuNP, bringing the dual fluorophores into close proximity, resulting in high FRET efficiency, which could be used as a signal for pH sensing. The nanoprobe possesses abilities of cellular transfection, enzymatic protection, fast response and quantitative pH detection. The in vitro and intracellular applications of the nanoprobe were demonstrated, which showed excellent response in the physiological pH range. Furthermore, our experimental results suggested that the nanoprobe showed excellent spatial and temporal resolution in living cells. We think that the ratiometric sensing strategy could potentially be applied to create a variety of new multicolor sensors for intracellular detection. PMID- 26272230 TI - Sexually Transmitted Pathogens, Depression, and Other Manifestations Associated with Premenstrual Syndrome. AB - This study investigated whether sexually transmitted infections and lifestyle variables are associated with premenstrual syndrome (PMS) as well as particular manifestations commonly associated with PMS. Data were gathered from medical records of 500 regularly cycling women. The following infectious agents were investigated: human papillomavirus, Chlamydia trachomatis, Neisseria gonorrheae, Gardnerella vaginalis, Candida albicans, and Trichomonas vaginalis. Bivariate tests and multivariate logistic regressions were used to evaluate whether these pathogens were associated with headache, pain, nausea, and depression. Chlamydia trachomatis was significantly associated with premenstrual syndrome (PMS) and two common manifestations of PMS: depression and pain. Trichomonas vaginalis was significantly correlated with headache and Gardnerella vaginalis with nausea. None of the illness manifestations was significantly associated with the tested lifestyle variables: dietary calcium supplementation, alcohol and drug use, exercise, and smoking. These associations provide a basis for assessment of infectious causation of PMS and several manifestations of illness that are commonly associated with PMS. PMID- 26272232 TI - Clopidogrel and CYP2C19: pharmacogenetic testing ready for clinical prime time? PMID- 26272233 TI - Circulating tumor DNA outperforms circulating tumor cells for KRAS mutation detection in thoracic malignancies. AB - BACKGROUND: Circulating biomarkers, such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), are both considered for blood-based mutation detection, but limited studies have compared them in a head-to-head manner. Using KRAS (Kirsten rat sarcoma viral oncogene homolog), we performed such a comparison in patients who underwent surgery for suspected lung cancer. METHODS: We recruited 93 patients, including 82 with lung cancer and 11 with benign diseases of the lung. Mutations were detected in codons 12 and 13 of KRAS in DNA extracted from CTCs, plasma, and matched tumors or lung tissues with custom-designed coamplification at lower denaturation temperature (COLD)-PCR assays, high resolution melt analysis (HRM), and commercial assays (Roche Cobas((r)) KRAS mutation test and Qiagen Therascreen((r)) pyrosequencing KRAS kit). RESULTS: With the Cobas mutation test, we identified KRAS mutations in 21.3% of tumors. Mutation analysis in matched CTC DNA and ctDNA samples by COLD-PCR/HRM assay revealed mutations in 30.5% (ctDNA) and 23.2% (CTC DNA) of patients with lung cancer. Combined results of different tests revealed KRAS-positive cases for 28% of tumors. The diagnostic sensitivity and specificity of KRAS mutation detection in tumors achieved with ctDNA was 0.96 (95% CI 0.81-1.00) and 0.95 (0.85-0.99), respectively. The diagnostic test performance was lower for CTC DNA, at 0.52 (0.34-0.73) and 0.88 (0.79-0.95). CONCLUSIONS: Our results support ctDNA as a preferential specimen type for mutation screening in thoracic malignancies vs CTC DNA, achieving greater mutation detection than either CTCs or limited amounts of tumor tissue alone. PMID- 26272234 TI - Detecting long-term drift in reagent lots. AB - BACKGROUND: Between-reagent lot verification is a routine laboratory exercise in which a set of samples is tested in parallel with an existing reagent lot and a candidate reagent lot (before the candidate lot is committed to test patient samples). The exercise aims to verify and maintain consistency in the analytical performance of a test. We examined the limitations of a routine between-reagent lot verification procedure in detecting long-term analytical drift and looked for a more sensitive alternative. METHOD: Via numerical simulations, we examined the statistical power of the current regression-based (weighted Deming regression) procedure for between-reagent lot verification in detecting proportional bias and constant bias. An alternative procedure applying the Student t-test to separately examine cumulative regression slopes and intercepts across multiple reagent lots was proposed and evaluated by numerical simulations. RESULTS: The regression based procedure had poor statistical power in detecting proportional bias and constant bias when small numbers of samples were used in each between-reagent lot verification exercise. Furthermore, the method failed to detect long-term drifts in analytical performance. The proposed approach based on the Student t-test can detect long-term (cumulative) drifts in regression slopes and intercepts. This method detected a mild downward drift in the serum sodium assay in our hospital that was missed by routine between-reagent lot verification. CONCLUSIONS: The proposed method objectively and systematically detects long-term proportional and constant bias separately. However, the statistical power of this procedure remains unsatisfactory when used with small sample sizes. Sharing of information between laboratories may provide sufficient statistical power to detect clinically important analytical shifts. PMID- 26272235 TI - Melatonin: an ancient molecule that makes oxygen metabolically tolerable. AB - Melatonin is remarkably functionally diverse with actions as a free radical scavenger and antioxidant, circadian rhythm regulator, anti-inflammatory and immunoregulating molecule, and as an oncostatic agent. We hypothesize that the initial and primary function of melatonin in photosynthetic cyanobacteria, which appeared on Earth 3.5-3.2 billion years ago, was as an antioxidant. The evolution of melatonin as an antioxidant by this organism was necessary as photosynthesis is associated with the generation of toxic-free radicals. The other secondary functions of melatonin came about much later in evolution. We also surmise that mitochondria and chloroplasts may be primary sites of melatonin synthesis in all eukaryotic cells that possess these organelles. This prediction is made on the basis that mitochondria and chloroplasts of eukaryotes developed from purple nonsulfur bacteria (which also produce melatonin) and cyanobacteria when they were engulfed by early eukaryotes. Thus, we speculate that the melatonin synthesizing actions of the engulfed bacteria were retained when these organelles became mitochondria and chloroplasts, respectively. That mitochondria are likely sites of melatonin formation is supported by the observation that this organelle contains high levels of melatonin that are not impacted by blood melatonin concentrations. Melatonin has a remarkable array of means by which it thwarts oxidative damage. It, as well as its metabolites, is differentially effective in scavenging a variety of reactive oxygen and reactive nitrogen species. Moreover, melatonin and its metabolites modulate a large number of antioxidative and pro oxidative enzymes, leading to a reduction in oxidative damage. The actions of melatonin on radical metabolizing/producing enzymes may be mediated by the Keap1 Nrf2-ARE pathway. Beyond its direct free radical scavenging and indirect antioxidant effects, melatonin has a variety of physiological and metabolic advantages that may enhance its ability to limit oxidative stress. PMID- 26272236 TI - Identifying the Most Informative Prediction Tool for Cancer-specific Mortality After Radical Prostatectomy: Comparative Analysis of Three Commonly Used Preoperative Prediction Models. AB - BACKGROUND: The D'Amico risk stratification, Cancer of the Prostate Risk Assessment (CAPRA) score, and Stephenson nomogram are widely used prediction tools for biochemical recurrence and survival after radical prostatectomy (RP). These models have not been compared with respect to cancer-specific mortality (CSM) prediction. OBJECTIVE: To validate and compare the prediction tools for 10 yr CSM. DESIGN, SETTING, AND PARTICIPANTS: Overall, 2485 prostate cancer patients underwent RP in a European tertiary care center. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Three preoperative models (D'Amico, CAPRA, and Stephenson) were compared in terms of their ability to predict 10-yr CSM; therefore, accuracy tests (area under the receiver operating characteristic curve [AUC]), calibration plots, and decision curve analysis (DCA) were assessed for each model. RESULTS AND LIMITATIONS: CSM at 10 yr was 3.6%. The AUC was 0.76, 0.77, and 0.80 for the D'Amico, CAPRA, and Stephenson models, respectively. In calibration plots, predicted probabilities were close to the observed probabilities for the D'Amico model but showed underestimation of CSM for the Stephenson nomogram and overestimation of CSM for the CAPRA score. DCA identified a benefit for the CAPRA score. These results apply to patients treated at a European tertiary care center. CONCLUSIONS: Despite good discriminatory power, all tested models had some shortcomings in terms of prediction of 10-yr CSM. All three models showed good performance in North American cohorts, but our results suggested a lack of generalizability to European patients. To overcome this issue, local recalibration of the variable weights could be performed. Another possibility is the development of more universal markers that are independent of regional practice differences or, alternatively, the development of better tools to quantify clinical practice differences. PATIENT SUMMARY: Prediction tools can predict cancer survival prior surgery, relying on points for age, prostate specific antigen levels, aggressiveness, and percentage of cancer at biopsy. These tools are reliable in North American patients but have shortcomings for identifying patients at high risk of prostate cancer death in Europe. PMID- 26272237 TI - A Single-centre Early Phase Randomised Controlled Three-arm Trial of Open, Robotic, and Laparoscopic Radical Cystectomy (CORAL). AB - BACKGROUND: Laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy (RARC) are increasingly popular, but high-level evidence for these techniques remains lacking. OBJECTIVE: To compare the outcomes of patients undergoing open radical cystectomy (ORC), RARC, and LRC. DESIGN, SETTING, AND PARTICIPANTS: From March 2009 to July 2012, 164 patients requiring radical cystectomy for muscle-invasive bladder cancer or high-risk non-muscle-invasive bladder cancer were invited to participate, with an aim of recruiting 47 patients into each arm. Overall, 93 were suitable for trial inclusion; 60 (65%) agreed and 33 (35%) declined. INTERVENTION: ORC, RARC, or LRC with extracorporeal urinary diversion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary end points were 30- and 90-d complication rates. Secondary end points were perioperative clinical, pathologic, and oncologic outcomes, and quality of life (QoL). The Fisher exact test and analysis of variance were used for statistical analyses. RESULTS AND LIMITATIONS: The 30-d complication rates (classified by the Clavien Dindo system) varied significantly between the three arms (ORC: 70%; RARC: 55%; LRC: 26%; p=0.024). ORC complication rates were significantly higher than LRC (p<0.01). The 90-d complication rates did not differ significantly between the three arms (ORC: 70%; RARC: 55%; LRC 32%; p=0.068). Mean operative time was significantly longer in RARC compared with ORC or LRC. ORC resulted in a slower return to oral solids than RARC or LRC. There were no significant differences in QoL measures. Major limitations are the small sample size and potential surgeon bias. CONCLUSIONS: The 30-d complication rates varied by type of surgery and were significantly higher in the ORC arm than the LRC arm. There was no significant difference in 90-d Clavien-graded complication rates between the three arms. PATIENT SUMMARY: We compared patients having open, robotic, or laparoscopic bladder removal surgery for bladder cancer and found no difference in Clavien graded complication rates at 90 d. PMID- 26272238 TI - Copper-Catalyzed Thioetherification Reactions of Alkyl Halides, Triphenyltin Chloride, and Arylboronic Acids with Nitroarenes in the Presence of Sulfur Sources. AB - In this article, we report three odorless methods for the thioarylation and thioalkylation of different nitroarenes using alkyl halides (Br, Cl), triphenyltin chloride, and arylboronic acids as the coupling partners. Triphenyltin chloride is capable of delivering all of its phenyl groups to the product. Depending on the reaction, sodium thiosulfate pentahydrate (Na2S2O3.5H2O), S8/KF, and S8/NaOH systems are found to be effective sources of sulfur in the presence of copper salts. The use of green solvents, inexpensive catalysts, and user-friendly starting materials has made these methods interesting from a green chemistry standpoint. PMID- 26272240 TI - Impaired functional differentiation for categories of objects in the ventral visual stream: A case of developmental visual impairment. AB - We report the case of a 14-year-old girl suffering from severe developmental visual impairment along with delayed language and cognitive development, and featuring a clear-cut dissociation between spared dorsal and impaired ventral visual pathways. Visual recognition of objects, including faces and printed words, was affected. In contrast, movement perception and visually guided motor control were preserved. Structural MRI was normal on inspection, but Voxel Based Morphometry (VBM) revealed reduced grey matter density in the mesial occipital and ventral occipito-temporal cortex. Functional MRI during the perception of line drawings uncovered impaired differentiation which is normally observed at even younger ages: no local category preferences could be identified within the occipito-temporal cortex for faces, houses, words or tools. In contrast, movement related activations appeared to be normal. Finally, those abnormalities evolved on the background of chronic bilateral occipital epileptic activity, including continuous spike-wave discharges during sleep, which may be considered as the primary cause of non-specific intellectual disability and visual impairment. PMID- 26272239 TI - Crossmodal enhancement in the LOC for visuohaptic object recognition over development. AB - Research has provided strong evidence of multisensory convergence of visual and haptic information within the visual cortex. These studies implement crossmodal matching paradigms to examine how systems use information from different sensory modalities for object recognition. Developmentally, behavioral evidence of visuohaptic crossmodal processing has suggested that communication within sensory systems develops earlier than across systems; nonetheless, it is unknown how the neural mechanisms driving these behavioral effects develop. To address this gap in knowledge, BOLD functional Magnetic Resonance Imaging (fMRI) was measured during delayed match-to-sample tasks that examined intramodal (visual-to-visual, haptic-to-haptic) and crossmodal (visual-to-haptic, haptic-to-visual) novel object recognition in children aged 7-8.5 years and adults. Tasks were further divided into sample encoding and test matching phases to dissociate the relative contributions of each. Results of crossmodal and intramodal object recognition revealed the network of known visuohaptic multisensory substrates, including the lateral occipital complex (LOC) and the intraparietal sulcus (IPS). Critically, both adults and children showed crossmodal enhancement within the LOC, suggesting a sensitivity to changes in sensory modality during recognition. These groups showed similar regions of activation, although children generally exhibited more widespread activity during sample encoding and weaker BOLD signal change during test matching than adults. Results further provided evidence of a bilateral region in the occipitotemporal cortex that was haptic-preferring in both age groups. This region abutted the bimodal LOtv, and was consistent with a medial to lateral organization that transitioned from a visual to haptic bias within the LOC. These findings converge with existing evidence of visuohaptic processing in the LOC in adults, and extend our knowledge of crossmodal processing in adults and children. PMID- 26272241 TI - Revealing deposition mechanism of colloid particles on human serum albumin monolayers. AB - Colloid particle deposition was applied in order to characterize human serum albumin (HSA) monolayers on mica adsorbed under diffusion transport at pH 3.5. The surface concentration of HSA was determined by a direct AFM imaging of single molecules. The electrokinetic characteristics of the monolayers for various ionic strength were done by in situ streaming potential measurements. In this way the mean-field zeta potential of monolayers was determined. It was shown that the initially negative potential changed its sign for HSA surface concentrations above 2800MUm(-2) that was interpreted as overcharging effect. The monolayers were also characterized by the colloid deposition method where negatively charged polystyrene particles, 810nm in diameter were used. The kinetics of particle deposition and their maximum coverage were determined as a function of the HSA monolayer surface concentration. An anomalous deposition of particles on substrates exhibiting a negative zeta potential was observed, which contradicts the mean-field theoretical predictions. This effect was quantitatively interpreted in terms of the random site sequential adsorption model. It was shown that efficient immobilization of particles only occurs at adsorption sites formed by three and more closely adsorbed HSA molecules. These results can be exploited as useful reference data for the analysis of deposition phenomena of bioparticles at protein monolayers that has practical significance for the regulation of the bioadhesive properties of surfaces. PMID- 26272242 TI - Pseudorhabdosynochus species (Monogenoidea, Diplectanidae) parasitizing groupers (Serranidae, Epinephelinae, Epinephelini) in the western Atlantic Ocean and adjacent waters, with descriptions of 13 new species. AB - Seventeen of twenty-three species of groupers collected from the western Atlantic Ocean and adjacent waters were infected with 19 identified species (13 new) of Pseudorhabdosynochus Yamaguti, 1958 (Dactylogyridea, Diplectanidae); specimens of the Spanish flag Gonioplectrus hispanus, coney Cephalopholis fulva, marbled grouper Dermatolepis inermis, mutton hamlet Alphestes afer, and misty grouper Hyporthodus mystacinus were not infected; the yellowmouth grouper Mycteroperca interstitialis and yellowfin grouper Mycteroperca venenosa were infected with unidentified species of Pseudorhabdosynochus; the Atlantic creolefish Paranthias furcifer was infected with an unidentified species of Diplectanidae that could not be accommodated in Pseudorhabdosynochus. The following species of Pseudorhabdosynochus are described or redescribed based entirely or in part on new collections: Pseudorhabdosynochus americanus (Price, 1937) Kritsky & Beverley Burton, 1986 from Atlantic goliath grouper Epinephelus itajara; Pseudorhabdosynochus yucatanensis Vidal-Martinez, Aguirre-Macedo & Mendoza Franco, 1997 and Pseudorhabdosynochus justinella n. sp. from red grouper Epinephelus morio; Pseudorhabdosynochus kritskyi Dyer, Williams & Bunkley Williams, 1995 from gag Mycteroperca microlepis; Pseudorhabdosynochus capurroi Vidal-Martinez & Mendoza-Franco, 1998 from black grouper Mycteroperca bonaci; Pseudorhabdosynochus hyphessometochus n. sp. from Mycteroperca interstitialis; Pseudorhabdosynochus sulamericanus Santos, Buchmann & Gibson, 2000 from snowy grouper Hyporthodus niveatus and Warsaw grouper Hyporthodus nigritus (new host record); Pseudorhabdosynochus firmicoleatus n. sp. from yellowedge grouper Hyporthodus flavolimbatus and snowy grouper H. niveatus; Pseudorhabdosynochus mcmichaeli n. sp., Pseudorhabdosynochus contubernalis n. sp., and Pseudorhabdosynochus vascellum n. sp. from scamp Mycteroperca phenax; Pseudorhabdosynochus meganmarieae n. sp. from graysby Cephalopholis cruentata; Pseudorhabdosynochus beverleyburtonae (Oliver, 1984) Kritsky & Beverley-Burton, 1986 from dusky grouper Mycteroperca marginata; Pseudorhabdosynochus mizellei n. sp. from red hind Epinephelus guttatus; Pseudorhabdosynochus williamsi n. sp. from rock hind Epinephelus adscensionis; Pseudorhabdosynochus bunkleywilliamsae n. sp. from Nassau grouper Epinephelus striatus; Pseudorhabdosynochus mycteropercae n. sp. from tiger grouper Mycteroperca tigris; and Pseudorhabdosynochus tumeovagina n. sp. from speckled hind Epinephelus drummondhayi. Pseudorhabdosynochus woodi n. sp. from red hind Epinephelus guttatus is described based on specimens from the US National Parasite Collection (USNPC). Drawings of the haptoral and copulatory sclerites of the type specimens in the USNPC of Pseudorhabdosynochus monaensis Dyer, Williams & Bunkley-Williams, 1994 from rock hind Epinephelus adscensionis are presented. Finally, a note confirming Pseudorhabdosynochus epinepheli Yamaguti, 1958 rather than its senior synonym Pseudorhabdosynochus epinepheli (Yamaguti, 1938) Kritsky & Beverley Burton, 1986 as the type species of Pseudorhabdosynochus is provided. PMID- 26272243 TI - The year of transparency: measuring quality of cardiac care. AB - The assessment of quality of care is becoming increasingly important in healthcare, both globally and in the Netherlands. The Dutch Minister of Health declared 2015 to be the year of transparency, thereby aiming to improve quality of care by transparent reporting of outcome data. With the increasing importance of transparency, knowledge on quality measurement will be essential for a cardiologist in daily clinical care. To that end, this paper provides a comprehensive overview of the Dutch healthcare structure, quality indicators and the current and future assessment of quality of cardiac care in the Netherlands. PMID- 26272244 TI - Factors associated with self-reported unprotected anal intercourse among men who have sex with men in Changsha city of Hunan province, China. AB - Men who have sex with men (MSM) in China are highly susceptible to HIV infection and HIV prevalence among Chinese MSM is rapidly increasing in recent years. Unprotected anal intercourse (UAI) is a major contributing factor of HIV transmission. This study aims to identify factors associated with UAI among MSM in Changsha city, China. A cross-sectional survey was conducted among 642 MSM in Changsha city from July 2009 to June 2011 via a venue-based sampling method. Data on socio-demographic characteristics, sexual behaviours and utilisation of HIV/AIDS services were collected to determine the associates of UAI in MSM. Among the 642 MSM, 184 (28.7%) reported having UAI with male partners at the last sexual episode. UAI was associated with the venues where MSM met other MSM, and having unprotected sex with female partners at last the sexual episode and in the past six months. In addition, UAI was significant associated with not being exposed to HIV interventions, including free condom, lubricant, HIV testing and counselling, and peer education. MSM who have UAI practice are more likely to have unprotected sex with female; hence, potentially bridging HIV to the general female population. Specific harm-reduction programmes are shown to have significant impacts in reducing UAI and should be scaled up among MSM in China. PMID- 26272245 TI - One-step production of darunavir solid dispersion nanoparticles coated with enteric polymers using electrospraying. AB - OBJECTIVES: The aim of this work was to investigate the feasibility of producing darunavir (DRV) solid dispersion nanoparticles coated with an enteric polymer in one single step using electrospraying. METHODS: The core-shell nanoparticles were made using coaxial electrospraying. A solution of DRV with hydroxypropyl methylcellulose in a mixture of organic solvents formed the core, while the shell was produced from an enteric polymer (Eudragit L100) dissolved in an organic solvent. The final particles were evaluated in terms of morphology, physical state, encapsulation efficiency and in-vitro dissolution. KEY FINDINGS: Nanoparticles of encapsulated DRV solid dispersions within Eudragit L100 were successfully prepared with high encapsulation efficiency (90%). The enteric coating layer reduced the percentage of DRV release in acidic medium in the in vitro dissolution test to less than 20%. CONCLUSIONS: This study showed the potential of coaxial electrospraying for encapsulating solid dispersions within core-shell structured nanoparticles. PMID- 26272248 TI - Rapid Identification and Quantification of Linear Olefin Isomers by Online Ozonolysis-Single Photon Ionization Time-of-Flight Mass Spectrometry. AB - The specific locations of the double bonds in linear olefins can facilitate olefin catalytic synthetic reactions to improve the quality of target olefin products. We developed a simple and efficient approach based on single photon ionization time-of-flight mass spectrometry (SPI-TOFMS) combined with online ozonolysis to identify and quantify the linear olefin double bond positional isomers. The online ozonolysis cleaved the olefins at the double bond positions that led to formation of corresponding characteristic aldehydes. The aldehydes were then detected by SPI-TOFMS to achieve unique spectrometric "fingerprints" for each linear olefin to successfully identify the isomeric ones. To accurately quantify the isomeric components in olefin mixtures, an algorithm was proposed to quantify three isomeric olefin mixtures based on characteristic ion intensities and their equivalent ionization coefficients. The relative concentration errors for the olefin components were lower than 2.5% while the total analysis time was less than 2 min. These results demonstrate that the online ozonolysis SPI-TOFMS has the potential for real-time monitoring of catalytic olefin synthetic reactions. PMID- 26272247 TI - Flavivirus RNA synthesis in vitro. AB - Establishment of in vitro systems to study mechanisms of RNA synthesis for positive strand RNA viruses have been very useful in the past and have shed light on the composition of protein and RNA components, optimum conditions, the nature of the products formed, cis-acting RNA elements and trans-acting protein factors required for efficient synthesis. In this review, we summarize our current understanding regarding the requirements for flavivirus RNA synthesis in vitro. We describe details of reaction conditions, the specificity of template used by either the multi-component membrane-bound viral replicase complex or by purified, recombinant RNA-dependent RNA polymerase. We also discuss future perspectives to extend the boundaries of our knowledge. PMID- 26272249 TI - The SnRK2-APC/C(TE) regulatory module mediates the antagonistic action of gibberellic acid and abscisic acid pathways. AB - Abscisic acid (ABA) and gibberellic acid (GA) antagonistically regulate many developmental processes and responses to biotic or abiotic stresses in higher plants. However, the molecular mechanism underlying this antagonism is still poorly understood. Here, we show that loss-of-function mutation in rice Tiller Enhancer (TE), an activator of the APC/C(TE) complex, causes hypersensitivity and hyposensitivity to ABA and GA, respectively. We find that TE physically interacts with ABA receptor OsPYL/RCARs and promotes their degradation by the proteasome. Genetic analysis also shows OsPYL/RCARs act downstream of TE in mediating ABA responses. Conversely, ABA inhibits APC/C(TE) activity by phosphorylating TE through activating the SNF1-related protein kinases (SnRK2s), which may interrupt the interaction between TE and OsPYL/RCARs and subsequently stabilize OsPYL/RCARs. In contrast, GA can reduce the level of SnRK2s and may promote APC/C(TE)-mediated degradation of OsPYL/RCARs. Thus, we propose that the SnRK2 APC/C(TE) regulatory module represents a regulatory hub underlying the antagonistic action of GA and ABA in plants. PMID- 26272250 TI - Flurbiprofen axetil increases arterial oxygen partial pressure by decreasing intrapulmonary shunt in patients undergoing one-lung ventilation. AB - PURPOSES: In the present study, we investigated whether flurbiprofen axetil (FA) alleviates hypoxemia during one-lung ventilation (OLV) by reducing the pulmonary shunt/total perfusion (Q s/Q t) ratio, and examined the relationship between the Q s/Q t ratio and the thromboxane B2 (TXB2)/6-keto-prostaglandin F1alpha (6-K PGF1alpha) ratio. METHODS: Sixty patients undergoing esophageal resection for carcinoma were randomly assigned to groups F and C (n = 30 for each group). FA and placebo were administered i.v. 15 min before skin incision in groups F and C, respectively. The partial pressure of arterial oxygen (PaO2) was measured and the Q s/Q t ratio was calculated. Serum TXB2, 6-K-PGF1alpha, and endothelin (ET) were measured by radioimmunoassay. The relationship between TXB2/6-K-PGF1alpha and Q s/Q t was investigated. RESULTS: Compared with group C, PaO2 was higher and the Q s/Q t ratio was lower during OLV in group F (P < 0.05). After treatment with FA, both serum TXB2 and 6-K-PGF1alpha decreased significantly (P < 0.05) but the TXB2/6-K-PGF1alpha ratio increased significantly (P < 0.01). Increases in the TXB2/6-K-PGF1alpha ratio were correlated with reductions in the Q s/Q t ratio during OLV in group F (r = -0.766, P < 0.01). There was no significant difference in serum ET between groups F and C. CONCLUSIONS: Treatment with FA reduced the Q s/Q t ratio and further increased the PaO2 level during OLV, possibly due to upregulation of the vasoactive agent TXB2/6-K-PGF1alpha ratio. PMID- 26272252 TI - Prospective, cross-sectional study on MSSA and MRSA colonisation in hospitalised children. AB - There is a global trend for an increase in prevalence of nasal methicillin resistant Staphylococcus aureus (MRSA) colonisation in children. A decade ago, MRSA colonisation was studied in Swiss paediatric hospitals and revealed an extraordinarily low proportion (<1 %). The primary goal of this study was to determine if the current proportion of nasal colonisation with MRSA in hospitalised children was still favourable. We aimed to screen all children from the age of 0-16 years admitted to the paediatric and surgical wards at the University Children's Hospital Basel (UKBB) during 8 pre-defined surveillance weeks. After obtaining consent, a nasal swab was taken and analysed for growth of S. aureus. Furthermore, a standardised questionnaire was completed by interview with a parent. Of 535 eligible children, 340 (64 %) were enrolled. Mean age was 6.2 years (median 4.3, IQR 1 to 11.25), 111 (33 %) children were colonised with S. aureus but no MRSA was found. CONCLUSION: The prevalence of MRSA in children admitted to the UKBB during this surveillance period was zero. General MRSA screening in hospitalised children continues to be unjustified in our area. WHAT IS KNOWN: * The prevalence of nasal methicillin-resistant Staphylococcus aureus (MRSA) colonisation in children is increasing in many regions worldwide. * Surveillance for MRSA colonisation in healthcare settings varies considerably. WHAT IS NEW: * Periodic and risk-factor-based surveillance for MRSA colonisation is sufficient when regional prevalence is low. PMID- 26272251 TI - Effect of carbamazepine or phenytoin therapy on blood level of intravenously administered midazolam: a prospective cohort study. AB - Dental treatment of intellectually disabled patients is frequently performed under general anesthesia or sedation. Many of these patients have epilepsy and are medicated with antiepileptic drugs (AEDs). Carbamazepine (CBZ) and phenytoin (PHT) are known to promote the metabolism of midazolam, and the blood levels of midazolam in patients medicated with CBZ or PHT may be different from those in healthy individuals. In this study, we clarified the influences of CBZ and PHT on the blood level of intravenously administered midazolam in patients medicated with CBZ or PHT. The subjects were divided into the following groups: not medicated with AEDs (control group), medicated with only CBZ or PHT (mono CBZ/PHT group), and medicated with CBZ or PHT or both and other AEDs (poly CBZ/PHT group). General anesthesia was achieved using midazolam, propofol, and remifentanil, and then the blood midazolam level was measured at 10, 30, and 60 min after intravenous midazolam administration. According to the results, the blood midazolam level was significantly lower in the mono and poly CBZ/PHT groups than in the control group. This finding suggests that intravenously administered midazolam may have a weaker effect in patients medicated with CBZ or PHT. PMID- 26272253 TI - A bundle with a preformatted medical order sheet and an introductory course to reduce prescription errors in neonates. AB - The objective of this study was to assess whether the introduction of a new preformatted medical order sheet coupled with an introductory course affected prescription quality and the frequency of errors during the prescription stage in a neonatal intensive care unit (NICU). Two-phase observational study consisting of two consecutive 4-month phases: pre-intervention (phase 0) and post intervention (phase I) conducted in an 11-bed NICU in a Swiss university hospital. Interventions consisted of the introduction of a new preformatted medical order sheet with explicit information supplied, coupled with a staff introductory course on appropriate prescription and medication errors. The main outcomes measured were formal aspects of prescription and frequency and nature of prescription errors. Eighty-three and 81 patients were included in phase 0 and phase I, respectively. A total of 505 handwritten prescriptions in phase 0 and 525 in phase I were analysed. The rate of prescription errors decreased significantly from 28.9% in phase 0 to 13.5% in phase I (p < 0.05). Compared with phase 0, dose errors, name confusion and errors in frequency and rate of drug administration decreased in phase I, from 5.4 to 2.7% (p < 0.05), 5.9 to 0.2% (p < 0.05), 3.6 to 0.2% (p < 0.05), and 4.7 to 2.1% (p < 0.05), respectively. The rate of incomplete and ambiguous prescriptions decreased from 44.2 to 25.7 and 8.5 to 3.2% (p < 0.05), respectively. CONCLUSION: Inexpensive and simple interventions can improve the intelligibility of prescriptions and reduce medication errors. WHAT IS KNOWN: Medication errors are frequent in NICUs and prescription is one of the most critical steps. CPOE reduce prescription errors, but their implementation is not available everywhere. WHAT IS NEW: Preformatted medical order sheet coupled with an introductory course decrease medication errors in a NICU. Preformatted medical order sheet is an inexpensive and readily implemented alternative to CPOE. PMID- 26272255 TI - Routine nail clipping leads to the diagnosis of amelanotic nail unit melanoma in a young construction worker. PMID- 26272254 TI - Increased left atrial size in obese children and its association with insulin resistance: a pilot study. AB - Subclinical cardiac abnormalities represent predisposing factors for cardiovascular disease (CVD) in obese subjects. The aim of this study was to evaluate early cardiac abnormalities in obese youth and the potential association with insulin resistance (IR). Thirty obese (12 males (M)/18 females (F); age = 11.5 +/- 2.4 years; body mass index (BMI)-standard deviation score (SDS) = +2.1 +/- 0.5) and 15 normal weight (10 M/5 F; age = 12.8 +/- 3.1 years; BMI-SDS = +0.3 +/- 0.9) children and adolescents underwent Doppler two-dimensional echocardiographic assessments of left atrial (LA) and ventricular (LV) geometry and LV diastolic function (peak early [E] and late waves, E wave deceleration time, myocardial flow velocities). Homeostasis model assessment of IR (HOMA-IR) was used as an IR index. LA size was increased in obese children, as indicated by higher LA diameter (4.9 +/- 0.5 vs 4.1 +/- 0.4 cm, p < 0.001), area (14.3 +/- 2.5 vs 10.7 +/- 2.0 cm(2), p < 0.001), and volume (33.8 +/- 10.6 vs 23.7 +/- 6.4 ml, p = 0.003). LV mass was also increased in obese children (87.0 +/- 16.6 vs 68.8 +/- 13.2 g, p = 0.003), who also showed subtle diastolic dysfunctions, as indicated by higher values of E (97.1 +/- 14.3 vs 86.2 +/- 11.9 cm/s, p = 0.02). All the above parameters were significantly associated with BMI-SDS (p < 0.05). In addition, HOMA-IR was independently associated with LA diameter, area, and volume (beta = 0.314, p = 0.040; beta = 0.415, p = 0.008; beta = 0.535, p = 0.001). CONCLUSION: Obese children feature increased LA size, which emerged to be mainly correlated to, and possibly driven by IR, suggesting an increased CVD risk. WHAT IS KNOWN: Left atrial and ventricular alterations have been reported in obese adults, and they represent predisposing factors for cardiovascular disease. There is some evidence suggesting that obese children show increased left ventricular mass and also increased atrial size, although with conflicting results. WHAT IS NEW: Obese normotensive children showed a moderately increased atrial size, subtle alterations in left cardiac diastolic function, and ventricular mass. An association between insulin resistance and left cardiac changes was found, although its mechanism remains to be determined. PMID- 26272257 TI - Metabolism and function of hepatitis B virus cccDNA: Implications for the development of cccDNA-targeting antiviral therapeutics. AB - Persistent hepatitis B virus (HBV) infection relies on the stable maintenance and proper functioning of a nuclear episomal form of the viral genome called covalently closed circular (ccc) DNA. One of the major reasons for the failure of currently available antiviral therapeutics to achieve a cure of chronic HBV infection is their inability to eradicate or inactivate cccDNA. In this review article, we summarize our current understanding of cccDNA metabolism in hepatocytes and the modulation of cccDNA by host pathophysiological and immunological cues. Perspectives on the future investigation of cccDNA biology, as well as strategies and progress in therapeutic elimination and/or transcriptional silencing of cccDNA through rational design and phenotypic screenings, are also discussed. This article forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for hepatitis B." PMID- 26272258 TI - Zinc dyshomeostasis during polymicrobial sepsis in mice involves zinc transporter Zip14 and can be overcome by zinc supplementation. AB - Integrity of the immune system is particularly dependent on the availability of zinc. Recent data suggest that zinc is involved in the development of sepsis, a life-threatening systemic inflammation with high death rates, but with limited therapeutic options. Altered cell zinc transport mechanisms could contribute to the inflammatory effects of sepsis. Zip14, a zinc importer induced by proinflammatory stimuli, could influence zinc metabolism during sepsis and serve as a target for therapy. Using cecal ligation-and-puncture (CLP) to model polymicrobial sepsis, we narrowed the function of ZIP14 to regulation of zinc homeostasis in hepatocytes, while hepatic leukocytes were mostly responsible for driving inflammation, as shown by higher expression of IL-1beta, TNFalpha, S100A8, and matrix metalloproteinase-8. Using Zip14 knockout (KO) mice as a novel approach, we found that ablation of Zip14 produced a delay in development of leukocytosis, prevented zinc accumulation in the liver, altered the kinetics of hypozincemia, and drastically increased serum IL-6, TNFalpha, and IL-10 concentrations following CLP. Hence, this model revealed that the zinc transporter ZIP14 is a component of the pathway for zinc redistribution that contributes to zinc dyshomeostasis during polymicrobial sepsis. In contrast, using the identical CLP model, we found that supplemental dietary zinc reduced the severity of sepsis, as shown by amelioration of cytokines, calprotectins, and blood bacterial loads. We conclude that the zinc transporter ZIP14 influences aspects of the pathophysiology of nonlethal polymicrobial murine sepsis induced by CLP through zinc delivery. The results are promising for the use of zinc and its transporters as targets for future sepsis therapy. PMID- 26272259 TI - Lactobacillus acidophilus counteracts enteropathogenic E. coli-induced inhibition of butyrate uptake in intestinal epithelial cells. AB - Butyrate, a key short-chain fatty acid metabolite of colonic luminal bacterial action on dietary fiber, serves as a primary fuel for the colonocytes, ameliorates mucosal inflammation, and stimulates NaCl absorption. Absorption of butyrate into the colonocytes is essential for these intracellular effects. Monocarboxylate transporter 1 (MCT1) plays a major role in colonic luminal butyrate absorption. Previous studies (Tan J, McKenzie C, Potamitis M, Thorburn AN, Mackay CR, Macia L. Adv Immunol 121: 91-119, 2014.) showed decreased MCT1 expression and function in intestinal inflammation. We have previously shown (Borthakur A, Gill RK, Hodges K, Ramaswamy K, Hecht G, Dudeja PK. Am J Physiol Gastrointest Liver Physiol 290: G30-G35, 2006.) impaired butyrate absorption in human intestinal epithelial Caco-2 cells due to decreased MCT1 level at the apical cell surface following enteropathogenic E. coli (EPEC) infection. Current studies, therefore, examined the potential role of probiotic Lactobacilli in stimulating MCT1-mediated butyrate uptake and counteracting EPEC inhibition of MCT1 function. Of the five species of Lactobacilli, short-term (3 h) treatment with L. acidophilus (LA) significantly increased MCT1-mediated butyrate uptake in Caco-2 cells. Heat-killed LA was ineffective, whereas the conditioned culture supernatant of LA (LA-CS) was equally effective in stimulating MCT1 function, indicating that the effects are mediated by LA-secreted soluble factor(s). Furthermore, LA-CS increased apical membrane levels of MCT1 protein via decreasing its basal endocytosis, suggesting that LA-CS stimulation of butyrate uptake could be secondary to increased levels of MCT1 on the apical cell surface. LA-CS also attenuated EPEC inhibition of butyrate uptake and EPEC-mediated endocytosis of MCT1. Our studies highlight distinct role of specific LA-secreted molecules in modulating colonic butyrate absorption. PMID- 26272260 TI - Effects of birth asphyxia on the modulation of pharyngeal provocation-induced adaptive reflexes. AB - Perinatal asphyxia and aerodigestive symptoms are troublesome. We tested the hypothesis that pharyngeal provocation alters proximal and distal aerodigestive reflex coordination and kinetics in infants with hypoxic ischemic encephalopathy (HIE), compared with healthy controls. Specifically, we characterized the sensory motor properties of pharyngeal provocation-induced effects on upper esophageal sphincter (UES) and lower esophageal sphincter (LES) reflexes. Ten orally fed controls (32.0 +/- 1.5 wk gestation) and 25 infants with HIE (38.1 +/- 0.4 wk gestation) were evaluated at 39.7 +/- 0.9 and 41.9 +/- 0.6 wk postmenstrual age respectively. Pharyngo-esophageal reflexes evoked upon graded water stimuli were tested using water-perfusion micromanometry methods. Analysis included sensory motor characteristics of pharyngeal reflexive swallow (PRS), pharyngo-UES contractile reflex (PUCR), esophageal body-waveform kinetics, and pharyngo-LES relaxation reflex (PLESRR). For controls vs. infants with HIE, median appearance, pulse, grimace, activity, respiration (APGAR) scores were 6 vs. 1 at 1 min (P < 0.001) and 8 vs. 3 at 5 min (P < 0.001). Upon pharyngeal- stimulation, HIE infants (vs. controls) had frequent PUCR (P = 0.01); increased UES basal tone (P = 0.03); decreased LES basal tone (P = 0.002); increased pharyngeal-waveforms per stimulus (P = 0.03); decreased frequency of LES relaxation (P = 0.003); and decreased proximal esophageal contractile amplitude (P = 0.002), with prolonged proximal esophageal contractile duration (P = 0.008). Increased tonicity and reactivity of the UES and dysregulation of LES may provide the pathophysiological basis for pooling of secretions, improper bolus clearance, and aspiration risk. Deficits in function at the nuclear or supranuclear level involving glossopharyngeal and vagal neural networks and respiratory regulatory pathways involved with aerodigestive protection may be contributory. PMID- 26272261 TI - Imaging approach to measuring small bowel motility. PMID- 26272262 TI - Methods for Dissecting Motivation and Related Psychological Processes in Rodents. AB - Motivational impairments are increasingly recognized as being critical to functional deficits and decreased quality of life in patients diagnosed with psychiatric disease. Accordingly, much preclinical research has focused on identifying psychological and neurobiological processes which underlie motivation . Inferring motivation from changes in overt behavioural responding in animal models, however, is complicated, and care must be taken to ensure that the observed change is accurately characterized as a change in motivation , and not due to some other, task-related process. This chapter discusses current methods for assessing motivation and related psychological processes in rodents. Using an example from work characterizing the motivational impairments in an animal model of the negative symptoms of schizophrenia, we highlight the importance of careful and rigorous experimental dissection of motivation and the related psychological processes when characterizing motivational deficits in rodent models . We suggest that such work is critical to the successful translation of preclinical findings to therapeutic benefits for patients. PMID- 26272263 TI - Polymorphism in apoptotic BAX (-248G>A) gene but not in anti-apoptotic BCL2 ( 938C>A) gene and its protein and mRNA expression are associated with cervical intraepithelial neoplasia. AB - HPV is associated with cervical cancer and plays a crucial role in tumor formation. Apoptosis is regulated by different pathways involving genes that either promote (BCL2 gene) or inhibit (BAX gene) cell death. Our goal was to determine whether the BCL2-938C>A (rs2279115) and BAX-248G>A (rs4645878) single nucleotide polymorphisms (SNPs) are associated with squamous intraepithelial neoplasia (SIL) risk, and whether their phenotypic expression was impaired in these lesions. Two hundred and thirty-one cases showing SIL were classified as low SIL (LSIL, n = 101) or high SIL (HSIL, n = 130), and control subjects (n = 266) with no gynecologically proven SIL were recruited. No statistical difference in the genotype and allelic frequency of the BCL-2-938C>A polymorphism was observed among the groups. BCL2-938C/A and A/A homozygotes carriers had higher distribution of BCL-2-expressing cells in stroma in the SIL group. BCL2 mRNA expression was not correlated with BCL2-938C>A SNPs in both groups. We did find a strong association of the BAX GG genotype and risk for SIL. No difference was observed between LSIL and HSIL groups. In BAX-248G/A and A/A homozygote carriers, the number of BAX-expressing cells was lower the epithelium area in SIL. However, mRNA expression was higher in SIL patients than in the control group. In conclusion, our data provide evidence that allele G carriers in the BAX-248G>A promoter SNP may influence the development of SIL. However, this genotype does not influence the SIL outcome. Additionally, we suggest a possible role of HPV infection in the inhibition of the expression of BAX protein, decreasing cell death, and favoring cervical carcinogenesis. PMID- 26272264 TI - Stabilisation of Fe2O3-rich Perovskite Nanophase in Epitaxial Rare-earth Doped BiFeO3 Films. AB - Researchers have demonstrated that BiFeO3 exhibits ferroelectric hysteresis but none have shown a strong ferromagnetic response in either bulk or thin film without significant structural or compositional modification. When remanent magnetisations are observed in BiFeO3 based thin films, iron oxide second phases are often detected. Using aberration-corrected scanning transmission electron microscopy, atomic resolution electron energy loss spectrum-mapping and quantitative energy dispersive X-ray spectroscopy analysis, we reveal the existence of a new Fe2O3-rich perovskite nanophase, with an approximate formula (Fe0.6Bi0.25Nd0.15)(3+) Fe(3+)O3, formed within epitaxial Ti and Nd doped BiFeO3 perovskite films grown by pulsed laser deposition. The incorporation of Nd and Bi ions on the A-site and coherent growth with the matrix stabilise the Fe2O3-rich perovskite phase and preliminary density functional theory calculations suggest that it should have a ferrimagnetic response. Perovskite-structured Fe2O3 has been reported previously but never conclusively proven when fabricated at high pressure high-temperature. This work suggests the incorporation of large A-site species may help stabilise perovskite-structured Fe2O3. This finding is therefore significant not only to the thin film but also to the high-pressure community. PMID- 26272266 TI - Effects of green tea (Camellia sinensis) mouthwash containing 1% tannin on dental plaque and chronic gingivitis: a double-blinded, randomized, controlled trial. AB - AIM: The aim of the present study was to explore the effects of Iranian green tea mouthwash containing 1% tannin on dental plaque and chronic gingivitis. METHODS: In this randomized, double-blinded, parallel, controlled clinical trial, 40 volunteer dental students with a gingival index >=1 were enrolled. At baseline, gingival, plaque, and bleeding indices were recorded and all the participants received dental polishing. Based on random allocation, 20 participants used the test and 20 used chlorhexidine mouthwash with no change in regular toothbrushing methods. The participants were asked to use 15 mL of the respective mouthwash for 1 min, twice a day for 28 days. All indices, as well as stain index, were recorded after 1 and 4 weeks post-rinsing. Data were analyzed using repeated measures ANOVA and Bonferroni tests. RESULTS: Significant in-group differences, but not between-group differences, were observed in all indices after 1 and 4 weeks compared to baseline. The test mouthwash resulted in significantly less tooth staining than the control. CONCLUSION: The 1% tannin green tea mouthwash could be a safe and feasible adjunct to mechanical plaque control. The tested green tea mouthwash could be considered a good alternative for chlorhexidine in contraindicating situations. PMID- 26272265 TI - Assessment of executive functioning in children and young adults treated for frontal lobe tumours using ecologically valid tests. AB - There is a lack of studies assessing executive functions (EF) using ecologically valid tests in children with frontal lobe lesions. This study aimed to (1) evaluate EF in children, adolescents and young adults treated for childhood frontal lobe tumours, (2) identify factors influencing performance, such as age at diagnosis or type of treatment, and (3) examine correlations between intellectual ability and classical and ecological tests of EF. Twenty-one patients, aged 8-27 years, treated for a childhood benign or malignant frontal lobe tumour, and 42 healthy controls (matched for gender, age and socio-economic status) were assessed using classical tests of EF, and the BADS-C ecological battery. Patients also underwent assessment of intellectual ability and parent and teacher ratings of the BRIEF questionnaire. IQ scores ranged from 45 to 125 (mean FSIQ = 84) and were lower in case of epilepsy, hydrocephalus and lower parental education. Patients displayed deficits in most, but not all measures of EF. Most classical and ecological measures of EF were strongly correlated to IQ. This study confirms the frequency of EF deficits in this population; it also highlights the utility of ecological measures of EF and some limitations of classical tests of EF in children. PMID- 26272268 TI - Synthesis of ([(11)C]carbonyl)raclopride and a comparison with ([(11)C]methyl)raclopride in a monkey PET study. AB - INTRODUCTION: The selective dopamine D2 receptor antagonist raclopride is usually labeled with carbon-11 using [(11)C]methyl iodide or [(11)C]methyl triflate for use in the quantification of dopamine D2 receptors in human brain. The aim of this work was to label raclopride at the carbonyl position using [(11)C]carbon monoxide chemistry and to compare ([(11)C]carbonyl)raclopride with ([(11)C]methyl)raclopride in non-human primate (NHP) using PET with regard to quantitative outcome measurement, metabolism of the labeled tracers and protein binding. METHODS: Palladium-mediated carbonylation using [(11)C]carbon monoxide, 4,6-dichloro-2-iodo-3-methoxyphenol and (S)-(-)-2-aminomethyl-1-ethylpyrrolidine was applied in the synthesis of ([(11)C]carbonyl)raclopride. The reaction was performed at atmospheric pressure using xantphos as supporting phosphine ligand and palladium (pi-cinnamyl) chloride dimer as the palladium source. ([(11)C]Methyl)raclopride was prepared by a previously published method. In the PET study, two female cynomolgus monkeys were used under gas anesthesia of sevoflurane. A dynamic PET measurement was performed for 63 min with an HRRT PET camera after intravenous injection of ([(11)C]carbonyl)raclopride and ([(11)C]methyl)raclopride, respectively, during the same day. The order of injection of the two PET radioligands was changed between the two monkeys. The venous blood sample for measurement of protein binding was taken 3 min prior to the PET scan. Binding potential (BPND) of the putamen and caudate was calculated with SRTM using the cerebellum as a reference region. RESULTS: The target compound ([(11)C]carbonyl)raclopride was obtained with 50 +/- 5% decay corrected radiochemical yield and 95% radiochemical purity. The trapping efficiency (TE) of [(11)C]carbon monoxide was 65 +/- 5% and the specific radioactivity of the final product was 34 +/- 1 GBq/MUmol after a 50 min of synthesis time. The radiochemical yield of ([(11)C]methyl)raclopride was in the same range as published previously i. e. 50-60% and specific radioactivity of those two batches which were used in the present PET study were 192 GBq/MUmol and 638 GBq/MUmol respectively after a synthesis time of 32 min. In monkey PET studies, the percentage difference of BPND in putamen was <3% and that in caudate was <9% for the two radioligands. The plasma protein binding was 86.2 +/- 0.3% and 85.7 +/- 0.6% for ([(11)C]carbonyl)raclopride and ([(11)C]methyl)raclopride, respectively. The radiometabolite pattern was similar for both radioligands. CONCLUSION: Raclopride was (11)C-labeled at the carbonyl position using a palladium-mediated [(11)C]carbonylation reaction. A comparison between ([(11)C]carbonyl)raclopride and ([(11)C]methyl)raclopride with regard to quantitative PET outcome measurements, metabolism of radioligands and protein binding in monkey was performed. The monkey PET study with ([(11)C]carbonyl)raclopride showed similar results as for ([(11)C]methyl)raclopride. The PET studies were performed on 2 subjects. PMID- 26272267 TI - The Impact of Social Media on Dissemination and Implementation of Clinical Practice Guidelines: A Longitudinal Observational Study. AB - BACKGROUND: Evidence-based clinical practice guidelines (CPGs) are statements that provide recommendations to optimize patient care for a specific clinical problem or question. Merely reading a guideline rarely leads to implementation of recommendations. The American Academy of Neurology (AAN) has a formal process of guideline development and dissemination. The last few years have seen a burgeoning of social media such as Facebook, Twitter, and LinkedIn, and newer methods of dissemination such as podcasts and webinars. The role of these media in guideline dissemination has not been studied. Systematic evaluation of dissemination methods and comparison of the effectiveness of newer methods with traditional methods is not available. It is also not known whether specific dissemination methods may be more effectively targeted to specific audiences. OBJECTIVE: Our aim was to (1) develop an innovative dissemination strategy by adding social media-based dissemination methods to traditional methods for the AAN clinical practice guidelines "Complementary and alternative medicine in multiple sclerosis" ("CAM in MS") and (2) evaluate whether the addition of social media outreach improves awareness of the CPG and knowledge of CPG recommendations, and affects implementation of those recommendations. METHODS: Outcomes were measured by four surveys in each of the two target populations: patients and physicians/clinicians ("physicians"). The primary outcome was the difference in participants' intent to discuss use of complementary and alternative medicine (CAM) with their physicians or patients, respectively, after novel dissemination, as compared with that after traditional dissemination. Secondary outcomes were changes in awareness of the CPG, knowledge of CPG content, and behavior regarding CAM use in multiple sclerosis (MS). RESULTS: Response rates were 25.08% (622/2480) for physicians and 43.5% (348/800) for patients. Awareness of the CPG increased after traditional dissemination (absolute difference, 95% confidence interval: physicians 36%, 95% CI 25-46, and patients 10%, 95% CI 1-11) but did not increase further after novel dissemination (physicians 0%, 95% CI -11 to 11, and patients -4%, 95% CI -6 to 14). Intent to discuss CAM also increased after traditional dissemination but did not change after novel dissemination (traditional: physicians 12%, 95% CI 2-22, and patients 19%, 95% CI 3-33; novel: physicians 11%, 95% CI -1 to -21, and patients -8%, 95% CI -22 to 8). Knowledge of CPG recommendations and behavior regarding CAM use in MS did not change after either traditional dissemination or novel dissemination. CONCLUSIONS: Social media-based dissemination methods did not confer additional benefit over print-, email-, and Internet-based methods in increasing CPG awareness and changing intent in physicians or patients. Research on audience selection, message formatting, and message delivery is required to utilize Web 2.0 technologies optimally for dissemination. PMID- 26272269 TI - Relationship between Insulin-Resistance Processing Speed and Specific Executive Function Profiles in Neurologically Intact Older Adults. AB - This study investigated the relationship between insulin-resistance and constituent components of executive function in a sample of neurologically intact older adult subjects using the homeostasis model assessment (HOMA-IR) and latent factors of working memory, cognitive control and processing speed derived from confirmatory factor analysis. Low-density lipoprotein (LDL), mean arterial pressure (MAP), along with body mass index (BMI) and white matter hypointensity (WMH) were used to control for vascular risk factors, adiposity and cerebrovascular injury. The study included 119 elderly subjects recruited from the University of California, San Francisco Memory and Aging Center. Subjects underwent neuropsychological assessment, fasting blood draw and brain magnetic resonance imaging (MRI). Partial correlations and linear regression models were used to examine the HOMA-IR-executive function relationship. Pearson correlation adjusting for age showed a significant relationship between HOMA-IR and working memory (rp = -.18; p = .047), a trend with cognitive control (rp = -.17; p = .068), and no relationship with processing speed (rp = .013; p = .892). Linear regression models adjusting for demographic factors (age, education, and gender), LDL, MAP, BMI, and WMH indicated that HOMA-IR was negatively associated with cognitive control (r = -.256; p = .026) and working memory (r = -.234; p = .054). These results suggest a greater level of peripheral insulin-resistance is associated with decreased cognitive control and working memory. After controlling for demographic factors, vascular risk, adiposity and cerebrovascular injury, HOMA-IR remained significantly associated with cognitive control, with working memory showing a trend. These findings substantiate the insulin-resistance executive function hypothesis and suggest a complex interaction, demonstrated by the differential impact of insulin-resistance on processing speed and specific aspects of executive function. PMID- 26272270 TI - N-acetyl-D-glucosamine kinase interacts with dynein light-chain roadblock type 1 at Golgi outposts in neuronal dendritic branch points. AB - N-acetylglucosamine kinase (GlcNAc kinase or NAGK) is a ubiquitously expressed enzyme in mammalian cells. Recent studies have shown that NAGK has an essential structural, non-enzymatic role in the upregulation of dendritogenesis. In this study, we conducted yeast two-hybrid screening to search for NAGK-binding proteins and found a specific interaction between NAGK and dynein light-chain roadblock type 1 (DYNLRB1). Immunocytochemistry (ICC) on hippocampal neurons using antibodies against NAGK and DYNLRB1 or dynein heavy chain showed some colocalization, which was increased by treating the live cells with a crosslinker. A proximity ligation assay (PLA) of NAGK-dynein followed by tubulin ICC showed the localization of PLA signals on microtubule fibers at dendritic branch points. NAGK-dynein PLA combined with Golgi ICC showed the colocalization of PLA signals with somal Golgi facing the apical dendrite and with Golgi outposts in dendritic branch points and distensions. NAGK-Golgi PLA followed by tubulin or DYNLRB1 ICC showed that PLA signals colocalize with DYNLRB1 at dendritic branch points and at somal Golgi, indicating a tripartite interaction between NAGK, dynein and Golgi. Finally, the ectopic introduction of a small peptide derived from the C-terminal amino acids 74-96 of DYNLRB1 resulted in the stunting of hippocampal neuron dendrites in culture. Our data indicate that the NAGK-dynein-Golgi tripartite interaction at dendritic branch points functions to regulate dendritic growth and/or branching. PMID- 26272271 TI - The Osborn wave: what have we learned? AB - The Osborn wave is a deflection with a dome-shaped configuration at the R-ST junction of the electrocardiogram. It is mainly encountered in hypothermic states but is also recognized in other nonhypothermic conditions. It has important prognostic implications that warrant its recognition by various health-care providers. Most important is its arrhythmogenic potential especially when observed in patients with myocardial ischemia where it was found to be a precursor of malignant ventricular arrhythmias. Herein, we provide a comprehensive review of the history, causes, electrocardiographic and electrophysiologic characteristics, as well as diagnostic and prognostic significance of the Osborn wave. PMID- 26272274 TI - Do Genes Matter in Treating Eye Disease? PMID- 26272273 TI - Effects of renin-angiotensin-aldosterone system inhibitors on mortality, hospitalization, and diastolic function in patients with HFpEF. A meta-analysis of 13 randomized controlled trials. AB - AIM: The purpose of this meta-analysis was to evaluate the effects of renin angiotensin-aldosterone system (RAAS) inhibitors on mortality, hospitalization, diastolic function, and exercise capacity in heart failure with preserved ejection fraction (HFpEF). METHODS: Thirteen randomized controlled trials (RCTs), totaling 12,532 patients with HFpEF, were selected. All-cause and cardiovascular mortality, all-cause and heart failure-related hospitalization, diastolic function, and the 6-min walk distance were assessed. The risk ratios (RR) of the dichotomous data, weighted mean difference (WMD) of continuous data, and 95 % confidence intervals (CI) were calculated to assess the effects of RAAS inhibitors. RESULTS: RAAS inhibitors significantly decreased heart failure related hospitalization (RR 0.89; 95 % CI 0.82-0.97; p = 0.01) and improved the diastolic function, as reflected in a reduced E/e' index (MD -1.38; 95 % CI -2.01 to -0.74; p < 0.0001). However, there were no beneficial effects on all-cause cardiovascular mortality and all-cause hospitalization. Other diastolic parameters had few changes compared with the controls. The 6-min walk distance was not improved by the use of RAAS inhibitors. CONCLUSION: In patients with HFpEF, RAAS inhibitors decreased heart-failure hospitalization and the E/e' index without affecting mortality, all-cause hospitalization, other diastolic function parameters, and the 6-min walk distance. PMID- 26272272 TI - [Progression and regression of atherosclerotic plaques. New results based on intracoronary ultrasound]. AB - Intravascular ultrasound has been established as the gold standard for analyzing alterations in coronary artery atherosclerosis during monitoring investigations. Cross-sectional imaging can be used to visualize the area of the lumen and the vessel size and the plaque size as the difference between them. New technology allows the 3-D reconstruction of the volume for prespecified vessel segments using specific algorithms. Investigations on the natural course demonstrated predominantly progression. Even regression of coronary atherosclerosis can be visualized and quantified. Regression can only be expected when the level of low density lipoprotein (LDL) cholesterol is below the critical level of 75 mg/dl. Prospective randomized studies with highly effective statins showed that regression occurred in up to two thirds of patients when LDL cholesterol was below a cut-off of 78 mg/dl and was, therefore, very close to the threshold, which was calculated based on investigations of the natural course. Although the absolute values for plaque volume are in the range of 1 % over 1-2 years, it must be taken into consideration that coronary artery diseases are chronic diseases and a 1 % change per year will correspond to an enormous effect on plaque growth of coronary vessels. The great success of statins in reducing cardiovascular events is due to the possibility for reduction of progression and induction of regression. New developments in medication will be measured against the effectiveness of statins. PMID- 26272275 TI - Epstein-Barr virus infection is strictly associated with the metastatic spread of sinonasal squamous-cell carcinomas. AB - BACKGROUND: Sinonasal squamous-cell carcinomas (SNSCC) are relatively rare. Thus, data regarding the rate of lymph node metastases are inconsistent in contrast with well-known high metastasis rates in squamous-cell carcinomas of the head and neck (HNSCC) (oral cavity, pharynx and larynx). Hence, the indication for elective neck dissection is difficult in SNSCC. The aim of this study was to assess common genetic alterations and EBV and HPV status as a function of metastasis in SNSCC and HNSCC. METHODS: We retrospectively analyzed 44 SNSCC and 65 HNSCC for TP53, EGFR, KRAS, PIK3CA and BRAF mutations using a high-resolution melting analysis followed by Sanger sequencing. EBV and HPV detection was performed using in situ hybridization for virus encoded RNA. Tumor-associated p16(INK4a) expression was visualized by immunohistochemistry and correlated with HPV infection. The mutation data, EBV and HPV status were statistically compared with the clinical data in SNSCC and HNSCC. RESULTS: TP53 mutations were exclusively associated with shorter survival in SNSCC (p=0.048). All the other markers had no effect on the metastasis rate and survival. In total, 20 of 44 SNSCC were EBV-positive. Only these EBV positive tumors developed lymph node or distant metastases (p=0.008). LMP1 was positive in 14/44 patients. When combining both methods significance for a correlation between EBV/LMP1 positive patients and metastases was even higher (p=0.001). CONCLUSION: In SNSCC, the presence of EBV is strictly associated with metastasis. We recommend an elective neck dissection in patients with EBV-positive SNSCC. PMID- 26272276 TI - Assessing the needs of siblings of persons with schizophrenia: A qualitative study from India. AB - There is a lack of studies on siblings of persons with schizophrenia (SOPS) in Asia. This study aims to explore the needs of SOPS in India. 15 SOPS participated in this qualitative explorative study. All the interviews were audio recorded and later transcribed. Data analysis was carried out using General Inductive Approach. Five themes emerged from the data: managing illness or socio occupational functioning; follow up services; informational needs; personal needs; and miscellaneous needs. SOPS in India have some distinctive needs. Identifying these needs might help in developing and designing specific psychosocial interventions for better management. PMID- 26272277 TI - Does metal pollution matter with C retention by rice soil? AB - Soil respiration, resulting in decomposition of soil organic carbon (SOC), emits CO2 to the atmosphere and increases under climate warming. However, the impact of heavy metal pollution on soil respiration in croplands is not well understood. Here we show significantly increased soil respiration and efflux of both CO2 and CH4 with a concomitant reduction in SOC storage from a metal polluted rice soil in China. This change is linked to a decline in soil aggregation, in microbial abundance and in fungal dominance. The carbon release is presumably driven by changes in carbon cycling occurring in the stressed soil microbial community with heavy metal pollution in the soil. The pollution-induced increase in soil respiration and loss of SOC storage will likely counteract efforts to increase SOC sequestration in rice paddies for climate change mitigation. PMID- 26272279 TI - Most cases of cow's milk allergy are able to ingest a partially hydrolyzed formula. PMID- 26272278 TI - Quality of life and nutritional consequences after aboral pouch reconstruction following total gastrectomy for gastric cancer: randomized controlled trial CCG1101. AB - BACKGROUND: Total gastrectomy has detrimental effects on postoperative nutritional status and quality of life (QOL), but it is often unavoidable in the treatment of gastric cancer. Roux-en-Y (RY) is the most common reconstruction method following total gastrectomy. Trials to explore other means of reconstruction have been conducted but have failed to identify a method that is globally accepted. METHODS: Aboral pouch reconstruction (AP), in which an anisoperistaltic jejunal pouch is created in the Y limb of the RY reconstruction, is considered effective and technically feasible. A prospective randomized trial was conducted to compare AP with RY. Gastric cancer patients requiring total gastrectomy for R0 resection were randomly assigned during surgery to receive either RY (n = 51) or AP (n = 49). Postoperative QOL as assessed by the EORTC QLQ C30 and STO22, body composition, and morbidity were compared between the two reconstruction methods. The physical functioning score of the QLQ-C30 was selected as the primary endpoint. RESULTS: The incidences of postoperative complications were similar between the two groups (29 % in the RY group and 27 % in the AP group). No significant difference was observed in the physical functioning score, and the superiority of AP was demonstrated only for the nausea and vomiting score at 12 months (p = 0.041) and the reflux score at 1 month (p = 0.036). No significant differences were observed in body composition or serum biochemistry. CONCLUSIONS: Although AP was safely implemented, no increased benefits in nutritional or QOL-related parameters were observed for this method over RY within 12 months postoperatively. PMID- 26272280 TI - Relationship between in utero C-reactive protein levels and asthma in at-risk children. AB - BACKGROUND: Asthma research has focused on postnatal exposures, but there is recent evidence to indicate atopic immune responses might be initiated in utero. Systemic inflammation during pregnancy might indicate an environment that could increase propensity in the child to develop allergic disease. OBJECTIVE: To investigate the association of systemic inflammation, as measured by C-reactive protein (CRP) levels, with asthma and wheezing in offspring within an at-risk, mostly Mexican, cohort. METHODS: Using data from a randomized education intervention of families at risk for asthma from 1998 followed through 2009 in urban Chicago, asthma was defined as ever having a physician diagnosis of asthma by 3 years of age and wheezing before the third year. Logistic regression models controlling for confounders investigated the effect of prenatal CRP levels on these outcomes. RESULTS: There were 244 mother-child pairs included in the study analysis with median prenatal CRP levels of 4.9 mg/L (interquartile range 3.2 7.7). Continuous prenatal CRP levels were predictive of asthma by year 3 (relative risk 2.4, 95% confidence interval 1.3, 3.6) and wheezing in year 3 (relative risk 1.7, 95% confidence interval 1.1, 2.4) after adjustment. Associations remained significant in mothers who were of Mexican ethnicity and were nonsmokers, suggesting that effects might be stronger in children at lower risk of disease. CONCLUSION: Prenatal CRP levels are associated with asthma by year 3 and wheezing in year 3 within a high-risk, urban, mostly Mexican, cohort. Maternal systemic inflammation might reflect a prenatal environment that could increase offspring susceptibility to develop wheezing and asthma young in life. PMID- 26272282 TI - Analysis of septic biomarker patterns: prognostic value in predicting septic state. AB - Patients with infection, sepsis, severe sepsis, or septic shock were compared to each other and to healthy controls with regard to serum levels of biomarkers and clinical symptoms. Of the 15 biomarkers assayed, 9 were detectable in patients, and 4, in controls. Both proinflammatory and anti-inflammatory cytokines were detected in the patients. No single biomarker could differentiate the 3 septic levels of severity from each other; however, interleukin (IL) 1 receptor antagonist (IL-1ra) had the best sensitivity and specificity for differentiating sepsis and severe sepsis from septic shock. IL-6 was the only cytokine able to differentiate infected patients without signs of sepsis from those with sepsis. Although IL-1ra, IL-6, IL-8, and monocyte chemoattractant protein 1 could differentiate infection, sepsis, and severe sepsis from septic shock, the biomarkers could not differentiate sepsis from severe sepsis. The top scoring pair algorithm with clinical and biomarker analyses was able to correctly diagnose those with sepsis who will progress to a more severe state. PMID- 26272281 TI - Efficacy and safety of a novel nasal steroid, S0597, in patients with seasonal allergic rhinitis. AB - BACKGROUND: Allergic rhinitis (AR) poses a significant global burden with increasing prevalence. Although intranasal glucocorticosteroids are effective, older agents can have limiting side effects. S0597, a novel intranasal glucocorticosteroid, has demonstrated good safety and tolerability during preclinical and phase 1 studies. OBJECTIVE: To assess the clinical efficacy, safety, and tolerability of different doses of S0597 nasal spray vs placebo in patients with seasonal AR. METHODS: This phase 2, randomized, double-blinded, placebo-controlled, parallel-group, single-center study randomized 159 patients 18 to 65 years old (mean age 37.8 years) with a positive skin prick test reaction for Dactylis glomerata to receive S0597 at 200, 400, or 800 MUg/d or placebo for 15 days. On days 1 (baseline), 15, and 16, patients underwent a 4-hour pollen challenge to evaluate treatment efficacy measured by the change in total nasal symptom score (TNSS) from baseline to days 15 and 16 and changes in TNSS subscales and nasal secretion. RESULTS: Statistically significant improvements in TNSS from baseline to days 15 and 16 were observed with all S0597 doses vs placebo (P = .0005 overall), with the greatest improvements observed in the highest-dose group (P < .0001). Significant decreases were observed in each S0597 dose group vs placebo for TNSS subscales and nasal secretion. Improvements in nasal secretion were related to dose, with the greatest decreases from baseline in the 800-MUg/d group on days 15 and 16 (P < .0001). CONCLUSION: Treatment with S0597 at 200, 400, and 800 MUg/d by 2 divided doses for 2 weeks was safe and significantly more effective than placebo for improving nasal symptoms associated with grass pollen-induced seasonal AR in adults. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT01614691. PMID- 26272283 TI - The synergy of berberine chloride and totarol against Staphylococcus aureus grown in planktonic and biofilm cultures. AB - Staphylococcus aureus (S. aureus) is commonly associated with hospital-acquired infections and is known to form biofilms. Bacteria inside biofilms display an increased resistance to chemotherapeutics and host immune defences. Efficient antibiotics or combination therapy are urgently needed to treat patients with biofilm-associated MRSA infections. The objective of the current study was to evaluate the in vitro antimicrobial activities of totarol alone or in combination with berberine chloride (BBR) against S. aureus grown in planktonic and biofilm cultures. The synergistic antimicrobial effects between BBR and totarol were observed in all tested strains grown in biofilms using a chequerboard microdilution method, with the fractional inhibitory concentration index values ranging from 0.125 to 0.375. No antagonistic activity was observed in any of the strains tested in suspension or biofilm cultures. The synergistic activity against S. aureus biofilms was also corroborated by confocal laser scanning microscopy and adhesion assays. Moreover, the present study demonstrated that combination BBR and totarol treatment effectively decreased the formation of S. aureus biofilms by affecting extracellular genomic DNA release and polysaccharide intercellular adhesin expression. Subsequently, real-time reverse transcriptase PCR analysis revealed that the combination of BBR and totarol effectively inhibited the transcription of the biofilm-related genes sarA, cidA and icaA. These results suggest that the combination of totarol and BBR is momentous for the further development of a therapy protocol against S. aureus biofilms. PMID- 26272284 TI - Association between cigarette smoking and Parkinson's disease: A meta-analysis. AB - OBJECTIVE: To evaluate the association of Parkinson's disease (PD) with smoking, and determine whether gender, source of controls, dose of smoking, and year of studies modify the observed effects of smoking on PD. METHODS: Available publications between 1959 and 2014 from PubMed, ScienceDirect, Springer Link and Web of Science databases were searched and carefully selected. Relative risks RR of specific study were weighted to obtain a pooled RR estimate and its 95% confidence interval CI. RESULTS: 61 case-control and 8 cohort studies were included. The pooled RR of PD was 0.59 (95% CI, 0.56-0.62) for ever smokers compared with never smokers. The stratified analyses indicated a somewhat greater impact of smoking on PD risk in cohort studies than in case-control studies, the protective effect was relatively significant in men more than in women and the inverse effect was slightly greater in hospital-based studies than in population based studies. Furthermore, a significant inverse dose-response relationship was observed for the number of pack-years smoked. The summary RR for those smoking more than 30 pack-years was 0.66 (95% CI, 0.49-0.88), and 0.39 (95% CI, 0.29 0.53) for those smoking less than 30 pack-years. CONCLUSION: The results demonstrated the inverse association between cigarette smoking and the risk of PD. We suggest that effective drugs for PD might be developed using chemical substances derived from tobacco or tobacco smoke. PMID- 26272285 TI - Major adverse cardiac events in elderly patients with coronary artery disease undergoing noncardiac surgery: A multicenter prospective study in China. AB - BACKGROUND: Major adverse cardiac events (MACEs) are important causes of perioperative morbidity and mortality for elderly patients undergoing non-cardiac surgery. Treatment and control rates for coronary artery disease (CAD) in Chinese patients are poorer than rates in western countries. However, no previous prospective study has focused on perioperative MACE in this population. Our aim was to ascertain the incidence and risk factors associated with MACEs in Chinese patients. METHODS: Consecutive CAD patients, aged >=60 years, who underwent non cardiac surgery at five medical centers in China, were prospectively enrolled. Clinical variables, including electrocardiogram and troponin I levels, were evaluated to estimate MACEs. The main outcome was occurrence of at least one perioperative MACE from admittance to 30 days after surgery, defined as any of the following complications: cardiac death, nonfatal cardiac arrest, acute myocardial infarction (MI), congestive heart failure (CHF), and angina. MACE independent risk factors were based on the Andersen-Gill multiplicative intensity model. RESULTS: Of the 1422 patients recruited, 129 (9.1%) developed at least one MACE, and cardiac death occurred in 11 patients (0.8%). The independent risk factors contributing to postoperative MACE included age >=75 years, female gender, history of MI, history of hypertension, high-risk surgery, intraoperative hypotension, and intraoperative hypoxemia. CONCLUSIONS: The incidence of MACE in Chinese elderly patients with CAD who underwent non-cardiac surgery was 9.1%. Seven independent risk factors for a perioperative MACE were identified. Preventing intraoperative hypoxemia and hypotension may reduce the occurrence of MACE in these high risk patients. PMID- 26272286 TI - Frailty syndrome and pre-operative risk evaluation: A systematic review. AB - BACKGROUND: Frailty is a geriatric syndrome characterized by the clinical presentation of identifiable physical alterations and decreased physiological reserve. The assessment of frailty syndrome has been recently related with post surgical outcomes and overall mortality in older individuals. DESIGN AND DATA SOURCES: We performed searches in Pubmed, Embase, Scopus, SCIELO and IME (Spanish medical index) databases from their start dates to February 2014 for original papers about the identification of the relationship between frailty and pre operative risk evaluation in people aged 65 and over. REVIEW METHODS: We followed criteria of systematic PRISMA guidelines. Two independent reviewers extracted descriptive information on frailty criteria and outcomes from the selected papers: of the 77 articles retrieved from the searches, 32 met the study inclusion criteria. RESULTS: Severity of frailty syndrome significantly correlated with post-surgical mortality rates and with many although not all post surgical complications. These relationships emerge in different type of surgical procedures and patients' features. The comparison of diagnostic tools to assess frailty in pre-operative risk evaluation are very few and to date, no recommendation can be made about the best scale to measure it. CONCLUSION: Assessment of frailty syndrome should be added in the pre-operative risk assessment in older individuals. PMID- 26272287 TI - Identification and characterization of the chromosomal yefM-yoeB toxin-antitoxin system of Streptococcus suis. AB - Toxin-antitoxin (TA) systems are widely prevalent in the genomes of bacteria and archaea. These modules have been identified in Escherichia coli and various other bacteria. However, their presence in the genome of Streptococcus suis, an important zoonotic pathogen, has received little attention. In this study, we describe the identification and characterization of a type II TA system, comprising the chromosomal yefM-yoeB locus of S. suis. The yefM-yoeB locus is present in the genome of most serotypes of S. suis. Overproduction of S. suis YoeB toxin inhibited the growth of E. coli, and the toxicity of S. suis YoeB could be alleviated by the antitoxin YefM from S. suis and Streptococcus pneumoniae, but not by E. coli YefM. More importantly, introduction of the S. suis yefM-yoeB system into E. coli could affect cell growth. In a murine infection model, deletion of the yefM-yoeB locus had no effect on the virulence of S. suis serotype 2. Collectively, our data suggested that the yefM-yoeB locus of S. suis is an active TA system without the involvement of virulence. PMID- 26272288 TI - Polychlorinated biphenyls (PCBs) in air and soil from a high-altitude pasture in the Italian Alps: evidence of CB-209 contamination. AB - This study analyses the seasonal trend of polychlorinated biphenyls (PCB) concentrations in air and soil from a high-altitude mountain pasture in the Italian Alps. PCB concentrations in soil were generally comparable to background levels and were lower than those previously measured in the same area. Only CB 209 unexpectedly showed high concentrations with respect to the other congeners. GC-MS-MS identification was very clear, rising a new problem of increasing PCB contamination concerning only CB-209, which is not present in commercial mixtures used in the past in Italy and Europe. Considering all of the congeners, seasonal PCB trends were observed both in air and in soil that were related to the temperature and precipitation measured specifically in the study area. Highly significant relationships were found between the temperature-normalised concentrations in soil and the precipitation amounts. A north/south enrichment factor was present only in soil with rapid early summer re-volatilisation kinetics from soil to air and autumn re-deposition events from air to soil. Fugacity ratio calculations confirmed these trends. Surface soils respond rapidly to meteorological variables, while subsurface soils respond much more slowly. Seasonal trends were different for the northern and southern sides of the mountain. A detailed picture of the interactions among temperature, precipitation, mountain aspects and soil features was obtained. PMID- 26272289 TI - Comparison of subcellular distribution and chemical forms of cadmium among four soybean cultivars at young seedlings. AB - The hydroponic experiment was carried out to investigate the Cd subcellular distribution and chemical forms in roots and shoots among four soybean seedling cultivars with two Cd treatments. HX3 and GC8, two tolerant and low-grain-Cd accumulating cultivars, had the lowest Cd concentration in roots and high Cd concentration in shoots, while BX10 and ZH24, two sensitive and high-grain-Cd accumulating cultivars, had the highest Cd concentration in roots and the lowest Cd concentration in shoots at young seedling stage. Furthermore, the sequence of Cd subcellular distribution in roots at two Cd levels was cell wall (53.4-75.5 %) > soluble fraction (15.8-40.4 %) > organelle fraction (2.0-14.7 %), but in shoots, was soluble fraction (39.3-74.8 %) > cell wall (16.0-52.0 %) > organelle (4.8-19.5 %). BX10 and ZH24 had higher Cd concentration in all subcellular fractions in roots, but HX3 and GC8 had higher Cd concentration of soluble fraction in shoots. The sequence of Cd chemical forms in roots was FNacl (64.1 79.5 %) > FHAC (3.4-21.5 %) > Fd-H2O (3.6-13.0 %) > Fethanol (1.4-21.8) > FHCl (0.3-1.6 %) > Fother (0.2-1.4 %) at two Cd levels but, in shoots, was FNacl (19.7 51.4 %) >= FHAC (10.2-31.4 %) >= Fd-H2O (8.8-28.2 %) >= Fethanol (8.9-38.6 %) > FHCl (0.2-9.6 %) > Fother (2.5-11.2 %). BX10 and ZH24 had higher Cd concentrations in each extracted solutions from roots, but from shoots for GC8 and HX3. Taken together, the results uncover that root cell walls and leaf vacuoles might play important roles in Cd detoxification and limiting the symplastic movement of Cd. PMID- 26272290 TI - Multistress effects on goldfish (Carassius auratus) behavior and metabolism. AB - Crossed effects between climate change and chemical pollutions were identified on community structure and ecosystem functioning. Temperature rising affects the toxic properties of pollutants and the sensitiveness of organisms to chemicals stress. Inversely, chemical exposure may decrease the capacity of organisms to respond to environmental changes. The aim of our study was to assess the individual and crossed effects of temperature rising and pesticide contamination on fish. Goldfish, Carassius auratus, were exposed during 96 h at two temperatures (22 and 32 degrees C) to a mixture of common pesticides (S metolachlor, isoproturon, linuron, atrazine-desethyl, aclonifen, pendimethalin, and tebuconazol) at two environmentally relevant concentrations (total concentrations MIX1 = 8.4 MUg L(-1) and MIX2 = 42 MUg L(-1)). We investigated the sediment reworking behavior, which has a major ecological functional role. We also focused on three physiological traits from the cellular up to the whole individual level showing metabolic status of fish (protein concentration in liver and muscle, hepatosomatic index, and Fulton's condition factor). Individual thermal stress and low concentrations of pesticides decreased the sediment reworking activity of fish and entrained metabolic compensation with global depletion in energy stores. We found that combined chemical and thermal stresses impaired the capacity of fish to set up an efficient adaptive response. Our results strongly suggest that temperature will make fish more sensitive to water contamination by pesticides, raising concerns about wild fish conservation submitted to global changes. PMID- 26272291 TI - The response and detoxification strategies of three freshwater phytoplankton species, Aphanizomenon flos-aquae, Pediastrum simplex, and Synedra acus, to cadmium. AB - The response and detoxification mechanisms of three freshwater phytoplankton species (the cyanobacterium Aphanizomenon flos-aquae, the green alga Pediastrum simplex, and the diatom Synedra acus) to cadmium (Cd) were investigated. The cell growth of each species was measured over 10 days, and chlorophyll a fluorescence, Cd bioaccumulation (including surface-adsorbed and intracellular Cd), and phytochelatin (PC) synthesis were determined after 96-h exposures. The growth of the three phytoplankton species was significantly inhibited when Cd concentrations were >=5 mg L(-1). Compared with P. simplex, greater growth inhibition in S. acus and A. flos-aquae occurred. The changes in chlorophyll fluorescence parameters including the maximal quantum yield of PSII (Fv/Fm) and relative variable fluorescence of the J point (Vj) demonstrated that the increase in Cd concentration damaged PSII in all three species. After 96-h exposures, the accumulation of surface-adsorbed Cd and intracellular Cd increased significantly in all three species, with the increase of Cd concentrations in the media; total cadmium accumulation was 245, 658, and 1670 times greater than that of the control in A. flos-aquae, P. simplex, and S. acus, respectively, after exposure to 10 mg L(-1). Total thiols exhibited a similar trend to that of Cd accumulation. PC3 was found in A. flos-aquae and P. simplex in all Cd treatments. Glutathione (GSH) and PC2 were also produced in response to exposure to high concentrations of Cd. PC4 was only discovered at exposure concentrations of 10 mg L(-1) Cd and only in S. acus. The intracellular Cd/PCs ratio increased in all three phytoplankton with an increase in Cd concentrations, and a linear relationship between the ratio and the growth inhibition rates was observed with P. simplex and S. acus. Our results have demonstrated that metal detoxification mechanisms were dependent on the species. This study suggested that the variance of metal detoxification strategies, such as cadmium accumulation and PCs, might be an explanation why algal species have different sensitivity to Cd at various levels. PMID- 26272292 TI - Differences in ozone photochemical characteristics between the megacity Nanjing and its suburban surroundings, Yangtze River Delta, China. AB - Rapid economic growth has led to a significant increase in ozone (O3) precursor emissions in many regions of China. Improved understanding of O3 formation in response to different precursor emissions is imperative to address the highly nonlinear O3 problem and to provide a solid scientific basis for efficient O3 abatement in these regions. A comparative study was conducted in summer using a set of observational data at urban and suburban sites in Nanjing. The results showed that high O3 concentrations were frequently encountered at both sites. The probability distributions of O3 in both sites show a fair resemblance to each other, suggesting strong regional mixing over the polluted Nanjing. A distinction between the characteristics of O3 precursors has been found at different sites. During the observation period, O3 concentrations varied monthly, reaching a minimum in June and peaking in August. The daily maximum O3 concentration was found to exceed 80 ppb for 27 days at residential area (RA), whereas it only exceeded 80 ppb for 22 days at industrial area (IA), 16 days at traffic area (TA), and 14 days at commercial area (CA). This pattern suggests a higher continuous ozone exposure risk at RA. The daily maximum O3 concentrations at different sites were 135.1 ppb (IA), 134.1 ppb (RA), 129.2 ppb (TA), and 110.6 ppb (CA), respectively. The daily maximum O3 concentration occurred at 16:00 in IA, at 17:00 in TA and CA, and at 18:00 in RA. Nitrogen dioxide (NO2) and carbon monoxide (CO) showed similar double-peak diurnal cycles. NO2 showed maximum values in June and minimum values in July. CO showed a similar diurnal variation to NO2. This effect may be explained by their common sources and the similar chemical losses. During the day, O3 tended to rapidly increase during the morning, reaching a maximum value of 9-11 ppb h(-1). The differences in O3 and NO2 between workdays and weekends were small. The CO levels were higher on weekdays than on weekends in urban areas and were higher on weekends than on weekdays in suburban areas. A sensitivity study performed with an observation based model (OBM) showed alkenes to be the largest contributor to O3 production. The production of O3 in the Nanjing area is generally limited by volatile organic compounds (VOCs), whereas high nitric oxide (NO) concentrations suppress O3 concentrations. PMID- 26272295 TI - Innate immunity: Memory NK cells identified in primates. PMID- 26272294 TI - Making the case for chromatin profiling: a new tool to investigate the immune regulatory landscape. AB - Recent technological advances have enabled researchers to accurately and efficiently assay the chromatin dynamics of scarce cell populations. In this Opinion article, we advocate the application of these technologies to central questions in immunology. Unlike changes to other molecular structures in the cell, chromatin features can reveal the past (developmental history), present (current activity) and future (potential response to challenges) of a given immune cell type; chromatin profiling is therefore an important new tool for studying the immune-regulatory networks of health and disease. PMID- 26272296 TI - Bacteria, inflammation and cancer. PMID- 26272293 TI - Synchronizing transcriptional control of T cell metabolism and function. AB - During an immune response, cytokines and transcription factors regulate the differentiation and function of effector and memory T cells. At the same time, T cell metabolism undergoes dynamic and differentiation-stage-specific changes that are required for initial T cell activation, rapid proliferation and the acquisition of effector functions. Similarly, during the resolution of an immune response, metabolic regulation is crucial for restraining inflammatory responses and promoting peripheral tolerance, and it is required for the long-term maintenance of memory T cells. T cell receptor (TCR)-induced transcription factors, in particular MYC and interferon-regulatory factor 4 (IRF4), cooperate with canonical nutrient-sensing pathways to integrate antigen-specific and metabolic signals to appropriately modulate adaptive immune responses. In this Review, we focus on the emerging evidence that T cell differentiation and metabolism are closely linked and synchronized by immune cell-specific cytokines and transcription factors that are induced by TCR signalling. PMID- 26272297 TI - Failure to rescue in colorectal surgery: How to minimize anastomotic leak mortality? PMID- 26272299 TI - [About "Factors determining irregular attendance to follow-up visits among human immunodeficiency virus patients: Results of a hospital survey of patients infected with human immunodeficiency virus, 2002-2012"]. PMID- 26272298 TI - Changing Patterns of Glucose-Lowering Medication Use in VA Nursing Home Residents With Diabetes, 2005 to 2011. AB - OBJECTIVE: Although nursing home (NH) residents make up a large and growing proportion of Americans with diabetes mellitus, little is known about how glucose lowering medications are used in this population. We sought to examine glucose lowering medication use in Veterans Affairs (VA) NH residents with diabetes between 2005 and 2011. RESEARCH DESIGN AND METHODS: Retrospective cohort study, using linked laboratory, pharmacy, administrative, and NH Minimum Dataset (MDS) 2.0 databases in 123 VA NHs. A total of 9431 long-stay (>90 days) VA NH residents older than 65 followed for 52,313 person-quarters. We identified receipt of glucose-lowering medications, including insulin, metformin, sulfonylureas, thiazolidinediones, and others (alpha-glucosidase inhibitors, meglitinides, glucagonlike peptide-1 analogs, dipeptidyl peptidase-4 inhibitors and amylin analogs) per quarter. RESULTS: The rates of sulfonylurea use in long-stay NH residents dropped dramatically from 24% in 2005 to 12% in 2011 (P < .001), driven in large part by the dramatic decrease in glyburide use (10% to 2%, P < .001). There was sharp drop in thiazolidinedione use in 2007 (4% to <1%, P < .001). Metformin use was stable, ranging between 7% and 9% (P = .24). Insulin use increased slightly from 30% to 32% (P < .001). Use of other classes of glucose lowering medications was stable (P = .22) and low, remaining below 1.3%. CONCLUSIONS AND RELEVANCE: Between 2005 and 2011, there were dramatic declines in use of sulfonylureas and thiazolidinediones in VA NH residents, suggesting that prescribing practices can be quickly changed in this setting. PMID- 26272300 TI - Structured movement representations of a phantom limb associated with phantom limb pain. AB - The relation between phantom limb pain (PLP) and the movement representation of a phantom limb remains controversial in several areas of neurorehabilitation, although there are a few studies in which the representation of phantom limb movement was precisely evaluated. We evaluated the structured movement representation of a phantom limb objectively using a bimanual circle-line coordination task. We then investigated the relation between PLP and the structured movement representation. Nine patients with a brachial plexus avulsion injury were enrolled who perceived a phantom limb and had neuropathic pain. While blindfolded, the participants repeatedly drew vertical lines using the intact hand and intended to draw circles using the phantom limb simultaneously. "Drawing of circles" by the phantom limb resulted in an oval transfiguration of the vertical lines ("bimanual coupling" effect). We used an arbitrary ovalization index (OI) to quantify the oval transfiguration. When the OI neared 100%, the trajectory changed toward becoming more circular. A significant negative correlation was observed between the intensity of PLP and the OI (r=-0.66, p<0.05). Our findings directly suggest that structured movement representations of the phantom limb are necessary for alleviating PLP. PMID- 26272301 TI - Perceiving emotions in human-human and human-animal interactions: Hemodynamic prefrontal activity (fNIRS) and empathic concern. AB - In the last years social neuroscience research attempted to identify the neural networks underlying the human ability to perceive others' emotions, a core process in establishing meaningful social bonds. A large amount of papers arose and identified common and specific empathy-based networks with respect to stimulus type and task. Despite the great majority of studies focused on human human contexts, we do not establish relations with only other humans, but also with non-human animals. The aim of the present work was to explore the brain mechanisms involved in empathic concern for people who interacts with both peers and other species. Participants have been assessed by functional near-infrared spectroscopy (fNIRS) while viewing pictures depicting humans interacting with both other men and women (human-human condition: HH), or with dogs and cats (human-animal: HA). Results showed that aggressive HH interactions elicited greater prefrontal activity (PFC) than HA ones while, when considering HA interactions, friendly ones were related to higher cortical activity. Finally, oxy (O2Hb) and deoxyhemoglobin (HHb) increasing related to the processing of aggressive interactions positively correlated with different empathic measures, within more specific brain regions. Results were elucidated with respect to available evidence on emotion perception, empathic neural mechanisms and their functional meaning for human-animal contexts. PMID- 26272302 TI - Self-assessment of competencies in dental education in Germany - a multicentred survey. AB - INTRODUCTION: The aim was to assess the competencies of undergraduate dental students in Germany in the domains team competence, communicative competence, learning competence and scholarship. MATERIALS AND METHODS: The survey was conducted at 11 dental schools that are equally distributed all over Germany. Competencies were assessed with the Freiburg Questionnaire to Assess Competencies in Medicine (FCM). A short version of the FCM was used in this study. This short form included the four domains: team competence (three items), communicative competence (eight items), learning competence (five items) and scholarship (four items). Students had to rate each item twice: first with regard to the respondent's current level of competence and second with regard to the level of competence that respondents think is required by their job. All items were rated on a five-point Likert scale (1 'very much' and 5 'not at all'). Responsible lecturers from all selected dental schools received another questionnaire to answer the questions whether the FCM domain corresponding learning objectives were taught at the respective dental school. RESULTS: A total of 317 undergraduate students from 11 dental schools in their last clinical year participated. The response rate varied between 48% and 92%. Cronbach's alpha for the FCM scales addressing the current level of competencies ranged from 0.70 to 0.89 and for the scales measuring the presumed level of competencies demanded by their job ranged from 0.72 to 0.82. The mean values of the scales for the assessment of the presumed level of competencies demanded by the job were significantly lower compared to the mean values of the scales for the current level of competencies (P < 0.001 in all analyses). We found large differences between the two levels - in terms of 'standardised response means' (SRM) - in the domains team competence (SRM 1.34), learning competence (SRM 1.27) and communicative competence (SRM 1.18). Overall, the learning objectives that correspond to the assessed domains of competencies were taught to 19.6% completely, to 55.4% partially and to 25% not at all at the participating dental schools. CONCLUSION: The results of the present survey revealed that the participating students perceived deficiencies in all domains of competencies. These results indicate that the assessed domains are still barely integrated into dental medicine curricula in Germany and that further research in this field is needed. PMID- 26272303 TI - Decreased level of cytotoxic T lymphocyte antigen-4 (CTLA-4) in patients with acute immune thrombocytopenia (ITP). AB - INTRODUCTION: Previously, we demonstrated the importance of T-cell immune response cDNA 7 (TIRC7) in acute immune thrombocytopenia (ITP). As the downstream molecule of TIRC7, cytotoxic T lymphocyte antigen-4 (CTLA-4) has been verified its negative regulation of acute ITP. This study aimed to investigate the exact role of CTLA-4 and its relationship with TIRC7 in acute ITP. PATIENTS AND METHODS: 37 patients with acute ITP were enrolled and received dexamethasone (40mg/day) for 4 consecutive days. Patients who had platelet counts more than 50*10(9)/L or less were defined as responders or non-responders after treatment. The plasma, protein and mRNA levels of CTLA-4 and TIRC7 were monitored by ELISA, western blot and q-PCR, respectively. RESULTS: After high-dose dexamethasone therapy, CTLA-4 levels were significantly elevated not only in acute ITP patients (P<0.001; P<0.0001) but also in acute ITP responders (P<0.0001; P<0.0001). The levels of CTLA-4 were negatively correlated with the levels of TIRC7 before and after treatment; IFN-gamma (Th1), IL-17 (Th17) and IL-22 (Th22) levels were all elevated, which were decreased after treatment not only in patients with acute ITP (P<0.01) but also in acute ITP responders (P<0.01). CONCLUSIONS: CTLA-4 level might reflect treatment efficacy and it might be associated with the pathogenesis of acute ITP. PMID- 26272304 TI - Elevated Semaphorin 5A correlated with Th1 polarization in patients with chronic immune thrombocytopenia. AB - BACKGROUND: Primary immune thrombocytopenia (ITP) is an immune-mediated disorder in which cellular immunity deficiency and disturbed cytokine profiles have been found. Semaphorin 5A (Sema5A) has been showed to be implicated in cellular immune response. We aimed to evaluate the role of Sema5A in patients with chronic ITP. METHODS: Plasma levels of Sema5A, T helper (Th) cytokines (interferon [IFN] gamma,interleukin [IL]-4,IL-17A) were determined by enzyme-linked immunosorbent assay (ELISA) in ITP patients and healthy controls. Using real-time quantitative polymerase chain reaction (RT-PCR), mRNA levels of Sema5A and its receptor plexin B3, plexin-A1 in peripheral blood mononuclear cells(PBMCs)were studied in all subjects. Specific anti-platelet autoantibodies were measured by the Pak Auto method. The dynamic change of plasma Sema5A and mRNA levels of its receptors was measured in 9 patients after effective therapy. RESULTS: Plasma Sema5A levels were significantly increased in active patients with chronic ITP compared to patients in remission and healthy controls. Elevated levels of Sema5A were found positively correlated with higher levels of plasma IFN-gamma, IFN-gamma/IL-4 ratio and negatively correlated with lower levels of plasma IL-4, platelet counts in ITP patients. The mRNA plexin-B3 was decreased in active ITP patients and inversely correlated with plasma Sema5A levels. Additionally, plasma levels of Sema5A and IFN-gamma were reduced with up-regulation of plexin-B3 expression after effective treatment. CONCLUSIONS: Our data demonstrated elevated plasma Sema5A in chronic ITP patients might be involved in Th1 polarization by down regulating receptor plexin-B3 expression and correlated with disease activity. PMID- 26272305 TI - Self-reported adherence to anticoagulation and its determinants using the Morisky medication adherence scale. AB - BACKGROUND: Direct oral anticoagulants (DOACs) are used for treatment of venous thromboembolism (VTE) and stroke prevention in atrial fibrillation (AF). Given the shorter half-life and lack of laboratory monitoring compared to vitamin-K antagonists (VKAs), adequate adherence to DOACs is important. Reported anticoagulation adherence is unclear in clinical practice. OBJECTIVES: To assess self-reported anticoagulation adherence in a tertiary center anticoagulation clinic. PATIENTS/METHODS: Cross-sectional study of patients on oral anticoagulants (VKAs, rivaroxaban, dabigatran and apixaban). Anticoagulation adherence was assessed using the 4-item Morisky score. Baseline characteristics were evaluated for association with adherence. RESULTS: Five hundred patients completed the survey; 74% were on VKAs and 26% on DOACs: rivaroxaban 102 (79%); dabigatran 26 (19%); apixaban 2 (2%). Main indications for anticoagulation were VTE (72%) and AF (18%). Self-reported anticoagulation adherence using the 4-item Morisky scale was 56.2% for patients on VKAs and 57.1% for patients on DOACs. Predictors of anticoagulation adherence were age (OR=1.02; 95% CI:1.01-1.03), female gender (OR=1.58; 95% CI:1.10-2.27), use of additional oral medications (OR=2.78; 95% CI:1.67-4.63), and retired employment status (OR=2.31; 95% CI:1.51 3.55). In backward selection multivariate analyses age, female gender and use of other oral medications remained significantly associated with anticoagulation adherence. CONCLUSIONS: Self-reported anticoagulation adherence was similar between VKAs and DOACs. Until laboratory assays are universally available to evaluate DOAC adherence, physicians should emphasize the importance of anticoagulation adherence at each patient encounter. The Morisky scale provides simple assessment of anticoagulation adherence; however it has not yet been validation for this purpose. PMID- 26272306 TI - Abnormal uterine bleeding in VTE patients treated with rivaroxaban compared to vitamin K antagonists. AB - INTRODUCTION: Rivaroxaban is a convenient oral anticoagulant for patients with venous thromboembolism (VTE). The impact of rivaroxaban and vitamin K antagonists (VKAs) on abnormal uterine bleeding (AUB) in real life has not been previously explored. MATERIALS AND METHODS: We performed a single-center retrospective study on AUB in female VTE patients of reproductive age who were treated with either rivaroxaban or VKAs. RESULTS: Questionnaire results were available for 52 patients in each treatment group. Approximately two thirds of all women reported AUB after initiation of anticoagulant therapy. Patients using rivaroxaban were more likely to experience prolonged (>8days) menstrual bleeding (27 % vs. 8.3%, P=0.017). Rivaroxaban treatment increased the duration of menstrual bleeding from median 5 (IQR 3.5-6.0) days before start of treatment to 6 (IQR 4.1-8.9) days (P<0.001). VKA treatment did not lead to significant prolongation of the menstrual period. Patients on rivaroxaban more frequently reported an unscheduled contact with a physician for AUB than women using VKAs (41% vs. 25%, P=0.096). They also reported increased need for menorrhagia-related medical or surgical intervention (25% vs. 7.7%, P=0.032) and had more adaptations of anticoagulant therapy (15% vs. 1.9%, P=0.031). CONCLUSION: AUB is frequent after initiation of anticoagulant therapy for acute symptomatic VTE. Compared to VKAs, rivaroxaban was associated with prolonged menstrual bleeding and more medical interventions and adaptation of anticoagulant treatment for AUB. These data can guide proactive discussion with patients starting anticoagulant therapy. PMID- 26272308 TI - Fabrication and applications of complex-shaped microparticles via microfluidics. AB - Complex-shaped microparticles (MPs) have attracted extensive interest in a myriad of scientific and engineering fields in recent years for their distinct morphology and capability in combining different functions within a single particle. Microfluidic techniques offer an intriguing method for fabricating MPs with excellent monodispersity and complex morphology in parallel while controlling their number and size precisely and independently. To date, there are two notable microfluidics approaches for the synthesis of complex-shaped MPs, namely droplet based, and flow-lithography based microfluidics approaches. It is undoubted that the application of complex-shaped MPs via microfluidic fabrication will hold great promise in a variety of fields including microfabrication, analytical chemistry and biomedicine. PMID- 26272307 TI - Pharmacogenomics of hypertension and heart disease. AB - Heart disease is a leading cause of death in the United States, and hypertension is a predominant risk factor. Thus, effective blood pressure control is important to prevent adverse sequelae of hypertension, including heart failure, coronary artery disease, atrial fibrillation, and ischemic stroke. Over half of Americans have uncontrolled blood pressure, which may in part be explained by interpatient variability in drug response secondary to genetic polymorphism. As such, pharmacogenetic testing may be a supplementary tool to guide treatment. This review highlights the pharmacogenetics of antihypertensive response and response to drugs that treat adverse hypertension-related sequelae, particularly coronary artery disease and atrial fibrillation. While pharmacogenetic evidence may be more robust for the latter with respect to clinical implementation, there is increasing evidence of genetic variants that may help predict antihypertensive response. However, additional research and validation are needed before clinical implementation guidelines for antihypertensive therapy can become a reality. PMID- 26272309 TI - Combined hormonal contraceptive use among women with known dyslipidemias: a systematic review of critical safety outcomes. AB - CONTEXT: Dyslipidemias represent a spectrum of lipid disorders that are important risk factors for cardiovascular disease. In addition, elevated triglycerides are known to be associated with pancreatitis. Though less clear, it is possible that dyslipidemias may also contribute to risk for venous thromboembolism (VTE). Ethinyl estradiol and progestogen, contained within combined hormonal contraception, are known to impact lipid metabolism. OBJECTIVES: To evaluate from the literature whether use of combined hormonal contraception (CHC), including combined oral contraception (COC) pills, transdermal patch, vaginal ring or injectables, modifies the relative risk of acute myocardial infarction (MI), stroke, VTE or pancreatitis among women with known dyslipidemias and to determine if existing lipid abnormalities worsen with CHC use. METHODS: PubMed and the Cochrane Library databases were searched for all articles in all languages published between inception and September 2014 relevant to dyslipidemia, CHC use and serious adverse events (MI, stroke, VTE or pancreatitis). The quality of each individual study was assessed using the system for grading evidence developed by the United States Preventive Services Task Force. RESULTS: From 306 articles identified by our search strategy, 3 articles met inclusion criteria. In a poor quality case-control study, women with hypercholesterolemia but no COC use had an increased risk of MI (adjusted odds ratio [adj OR] 3.3, 95% confidence interval [CI] 1.6-6.8), as did women who used COCs but did not have hypercholesterolemia (adj OR 2.0, 95% CI 1.4-2.8), compared with non-COC users without hypercholesterolemia; women with both COC use and hypercholesterolemia had an adjusted OR of 24.7 (95% CI 5.6-108.5) compared with women with neither risk factor. A poor-quality cohort study examined COC users and reported that women with dyslipidemia had increased risk for VTE [crude risk ratio (RR) 1.39, 95% CI 1.04-1.85] and transient ischemic attacks or cerebrovascular accidents (CVAs) (RR 1.76, 95% CI 1.51-2.06) compared to those without dyslipidemia. Another poor quality cohort study provided direct evidence on changes in lipid levels among COC users with dyslipidemia. A minority of women with elevated total cholesterol or triglyceride levels at baseline showed normal results (25% and 28%, respectively) after 6 cycles of COC use. No evidence regarding risks associated with use of other CHC methods was identified. No evidence was identified for the outcome of pancreatitis. CONCLUSION: Limited data from poor-quality observational studies suggest that women with known dyslipidemias using CHC may be at increased risk for MI and may experience a minimal increase in risk for CVA or VTE. No evidence was identified on risk for pancreatitis in this context. The impact of CHC exposure on the status of lipid abnormalities over time, an intermediate marker for disease, is also unclear. Given the significant limitations of this body of evidence, the importance of access to effective contraception and theoretical concerns raised about the use of CHCs by women with known dyslipidemias, additional rigorous studies are needed to best estimate true associations. Contraceptive decision making should include consideration of both the known and theoretical risks of a given CHC method, safety and acceptability of alternative contraceptive methods, and risks associated with unintended pregnancy. PMID- 26272310 TI - Tenth anniversary of the Society of Family Planning. PMID- 26272311 TI - Fisetin Alleviates Lipopolysaccharide-Induced Acute Lung Injury via TLR4-Mediated NF-kappaB Signaling Pathway in Rats. AB - Acute lung injury (ALI), a common component of systemic inflammatory disease, is a life-threatening condition without many effective treatments. Fisetin, a natural flavonoid from fruits and vegetables, was reported to have wide pharmacological properties such as anti-inflammatory, antioxidant, and anticancer activities. The aim of this study was to detect the effects of fisetin on lipopolysaccharide (LPS)-induced acute lung injury and investigate the potential mechanism. Fisetin was injected (1, 2, and 4 mg/kg, i.v.) 30 min before LPS administration (5 mg/kg, i.v.). Our results showed that fisetin effectively reduced the inflammatory cytokine release and total protein in bronchoalveolar lavage fluids (BALF), decreased the lung wet/dry ratios, and obviously improved the pulmonary histology in LPS-induced ALI. Furthermore, fisetin inhibited LPS induced increases of neutrophils and macrophage infiltration and attenuated MPO activity in lung tissues. Additionally, fisetin could significantly inhibit the Toll-like receptor 4 (TLR4) expression and the activation of NF-kappaB in lung tissues. Our data indicates that fisetin has a protective effect against LPS induced ALI via suppression of TLR4-mediated NF-kappaB signaling pathways, and fisetin may be a promising candidate for LPS-induced ALI treatment. PMID- 26272312 TI - Sagittal balance of the spine in patients with osteoporotic vertebral fractures. AB - This study aims to compare the sagittal global spinal balance of patients consulting for osteoporosis, aged above 50 years with and without osteoporotic vertebral fractures (VFs). Global spinal balance is abnormal even in subjects without VFs. VFs and age are determinants of sagittal global balance; however, pelvic parameters play a role in compensatory mechanisms. INTRODUCTION: This study aims to compare the spine curvatures, pelvic parameters, and the sagittal global spinal balance of patients aged above 50 years with and without osteoporotic vertebral fractures. METHODS: Two hundred patients (95 % women) aged 68.3 +/- 9.5 years underwent full skeleton radiographs in the standing position, by EOS(r), a low dose biplane X-ray imaging system. VFs were evaluated according to Genant's classification. Spinal (thoracic and lumbar Cobb's indices, thoracic and lumbar tilts) and pelvic (pelvic tilt, sacral slope, and pelvic incidence) parameters were measured. Sagittal spinal balance was measured using the C7 plumb line and the spinosacral angle (SSA). We compared these parameters in patients with and without vertebral fracture and assessed the determinants of abnormal sagittal spinal balance. RESULTS: Sixty-nine patients had at least one VF. The sagittal spinal balance was significantly altered in patients with at least one VF, and there was an effect of the number and severity of VFs on parameters. Discriminative value for identification of patients with at least one VF, assessed by Area Under the Curves (AUCs) was 0.652 and 0.706 for C7 plumbline and SSA, respectively. Using multivariate analysis, parameters significantly associated with abnormal spinal balance (SSA) were the presence of at least one VF (OR = 4.96, P < 0.0001), age (OR = 1.07, P = 0.0006), and high pelvic incidence as a protective factor (OR = 0.93, P < 0.0001). CONCLUSIONS: Global spinal balance is abnormal in subjects consulting for osteoporosis, even in subjects without VFs. VFs and age are determinants of abnormal sagittal global balance; however, pelvic parameters play a role in compensatory mechanisms. PMID- 26272313 TI - In vivo effects of two novel ALN-EP4a conjugate drugs on bone in the ovariectomized rat model for reversing postmenopausal bone loss. AB - Two alendronate-EP4 agonist (ALN-EP4a) conjugate drugs, C1 and C2, which differ in structure by a short linker molecule, were evaluated in ovariectomized (OVX) rats for their anabolic effects. We showed that C1 led to significant anabolic effects on cortical and trabecular bone while anabolic effects associated with C2 were minimal. INTRODUCTION: EP4as were covalently linked to ALN to create ALN EP4a conjugate anabolic bone drugs, C1 and C2, which differ in structure by a short linker molecule in C1. When administered systemically, C1 and C2 are delivered to bone through targeted binding of ALN, where local hydrolytic enzymes liberate EP4a from ALN to exert anabolic effects. Here, we compare effects of C1 to C2 in a curative in vivo study. METHODS: Three-month-old female Sprague Dawley rats were OVX or sham operated and allowed to lose bone for 3 months. Animals were then treated via tail vein injections for 3 months and sacrificed. Treatment groups were as follows: C1L (5 mg/kg biweekly), C1H (5 mg/kg weekly), C2L (15 mg/kg monthly), C2H (15 mg/kg biweekly), OVX and sham control (phosphate-buffered saline (PBS) biweekly), and ALN/EP4a-unconjugated mixture (0.75 mg/kg each biweekly). RESULTS: MicroCT analysis showed that C1H treatment significantly increased vertebral bone mineral density (vBMD) and trabecular bone volume versus OVX controls while C2 treatments did not. Biomechanical testing showed that C1H treatment but not C2 treatments led to significant improvement in the load bearing abilities of the vertebrae compared to OVX controls. C1 stimulated endocortical bone formation and increased load bearing in femurs, while C2 did not. CONCLUSIONS: We showed that C1 led to significant anabolic effects on cortical and trabecular bone while anabolic effects associated with C2 were minimal. These results led us to hypothesize a mode of action by which presence of a linker is crucial in facilitating the anabolic effects of EP4a when dosed as a prodrug with ALN. PMID- 26272314 TI - Antiepileptic drug prescribing before, during and after pregnancy: a study in seven European regions. AB - PURPOSE: The aim of this study was to explore antiepileptic drug (AED) prescribing before, during and after pregnancy as recorded in seven population based electronic healthcare databases. METHODS: Databases in Denmark, Norway, the Netherlands, Italy (Emilia Romagna/Tuscany), Wales and the Clinical Practice Research Datalink, representing the rest of the UK, were accessed for the study. Women with a pregnancy starting and ending between 2004 and 2010, which ended in a delivery, were identified. AED prescriptions issued (UK) or dispensed (non-UK) at any time during pregnancy and the 6 months before and after pregnancy were identified in each of the databases. AED prescribing patterns were analysed, and the choice of AEDs and co-prescribing of folic acid were evaluated. RESULTS: In total, 978 957 women with 1 248 713 deliveries were identified. In all regions, AED prescribing declined during pregnancy and was lowest during the third trimester, before returning to pre-pregnancy levels by 6 months following delivery. For all deliveries, the prevalence of AED prescribing during pregnancy was 51 per 10 000 pregnancies (CI95 49-52%) and was lowest in the Netherlands (43/10 000; CI95 33-54%) and highest in Wales (60/10 000; CI95 54-66%). In Denmark, Norway and the two UK databases lamotrigine was the most commonly prescribed AED; whereas in the Italian and Dutch databases, carbamazepine, valproate and phenobarbital were most frequently prescribed. Few women prescribed with AEDs in the 3 months before pregnancy were co-prescribed with high-dose folic acid: ranging from 1.0% (CI95 0.3-1.8%) in Emilia Romagna to 33.5% (CI95 28.7-38.4%) in Wales. CONCLUSION: The country's differences in prescribing patterns may suggest different use, knowledge or interpretation of the scientific evidence base. The low co-prescribing of folic acid indicates that more needs to be done to better inform clinicians and women of childbearing age taking AEDs about the need to offer and receive complete preconception care. PMID- 26272315 TI - Locomotor muscle fatigue is not critically regulated after prior upper body exercise. AB - This study examined the effects of prior upper body exercise on subsequent high intensity cycling exercise tolerance and associated changes in neuromuscular function and perceptual responses. Eight men performed three fixed work-rate (85% peak power) cycling tests: 1) to the limit of tolerance (CYC); 2) to the limit of tolerance after prior high-intensity arm-cranking exercise (ARM-CYC); and 3) without prior exercise and for an equal duration as ARM-CYC (ISOTIME). Peripheral fatigue was assessed via changes in potentiated quadriceps twitch force during supramaximal electrical femoral nerve stimulation. Voluntary activation was assessed using twitch interpolation during maximal voluntary contractions. Cycling time during ARM-CYC and ISOTIME (4.33 +/- 1.10 min) was 38% shorter than during CYC (7.46 +/- 2.79 min) (P < 0.001). Twitch force decreased more after CYC (-38 +/- 13%) than ARM-CYC (-26 +/- 10%) (P = 0.004) and ISOTIME (-24 +/- 10%) (P = 0.003). Voluntary activation was 94 +/- 5% at rest and decreased after CYC (89 +/- 9%, P = 0.012) and ARM-CYC (91 +/- 8%, P = 0.047). Rating of perceived exertion for limb discomfort increased more quickly during cycling in ARM-CYC [1.83 +/- 0.46 arbitrary units (AU)/min] than CYC (1.10 +/- 0.38 AU/min, P = 0.003) and ISOTIME (1.05 +/- 0.43 AU/min, P = 0.002), and this was correlated with the reduced cycling time in ARM-CYC (r = -0.72, P = 0.045). In conclusion, cycling exercise tolerance after prior upper body exercise is potentially mediated by central fatigue and intolerable levels of sensory perception rather than a critical peripheral fatigue limit. PMID- 26272316 TI - Tetraplegia is associated with enhanced peripheral chemoreflex sensitivity and ventilatory long-term facilitation. AB - Cardiorespiratory plasticity induced by acute intermittent hypoxia (AIH) may contribute to recovery following spinal cord injury (SCI). We hypothesized that patients with cervical SCI would demonstrate higher minute ventilation (Ve) following AIH compared with subjects with thoracic SCI and able-bodied subjects who served as controls. Twenty-four volunteers (8 with cervical SCI, 8 with thoracic SCI, and 8 able-bodied) underwent an AIH protocol during wakefulness. Each subject experienced 15 episodes of isocapnic hypoxia using mixed gases of 100% nitrogen (N2), 8% O2, and 40% CO2 to achieve oxygen saturation <=90% followed by room air (RA). Measurements were obtained before, during, and 40 min after AIH to obtain ventilation and heart rate variability data [R-R interval (RRI) and low-frequency/high-frequency power (LF/HF)]. AIH results were compared with those of sham studies conducted in RA during the same time period. Individuals with cervical SCI had higher Ve after AIH compared with able-bodied controls (117.9 +/- 23.2% vs. 97.9 +/- 11.2%, P < 0.05). RRI decreased during hypoxia in all individuals (those with cervical SCI, from 1,009.3 +/- 65.0 ms to 750.2 +/- 65.0 ms; those with thoracic SCI, from 945.2 +/- 65.0 ms to 674.9 +/- 65.0 ms; and those who were able-bodied, from 949 +/- 75.0 to 682.2 +/- 69.5 ms; P < 0.05). LH/HF increased during recovery in individuals with thoracic SCI and those who were able-bodied (0.54 +/- 0.22 vs. 1.34 +/- 0.22 and 0.67 +/- 0.23 vs. 1.82 +/- 0.23, respectively; P < 0.05) but remained unchanged in the group with cervical SCI. Our conclusion is that patients with cervical SCI demonstrate ventilatory long-term facilitation following AIH compared with able-bodied controls. Heart rate responses to hypoxia are acutely present in patients with cervical SCI but are absent during posthypoxic recovery. PMID- 26272317 TI - Regular exercise improves cardiac contractile activation by modulating MHC isoforms and SERCA activity in orchidectomized rats. AB - Data from the trial known as Testosterone in Older Men with Mobility Limitations (TOM) has indicated an association between testosterone administration and a greater risk for adverse cardiovascular events. We therefore propose that regular exercise is a cardioprotective alternative that prevents detrimental changes in contractile activation when a deficiency in male sex hormones exists. Ten-week old orchidectomized (ORX) rats were subjected to a 9-wk treadmill running program at moderate intensity starting 1 wk after surgery. Although exercise-induced cardiac hypertrophy was observed both in rats that underwent ORX and sham surgery, regular exercise enhanced cardiac myofilament Ca(2+) sensitivity and myosin light-chain 2 phosphorylation only in rats that underwent a sham operation. Although the rats that had sham surgery and and given exercise exhibited no change in maximum developed tension, regular running prevented the suppression of maximum active tension in the hearts of ORX rats. Regular exercise also prevented a shift in myosin heavy chain (MHC) isoforms toward beta-MHC, a reduction in sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) activity, and an increase in SERCA sensitivity in the hearts of ORX rats. Neither SERCA content nor its modulating component, phospholamban (PLB), was altered by exercise in either sham-operated or ORX rats. However, decreases in the phosphorylated Thr(17) form of PLB and the phosphorylated Thr(287) form of Ca(2+)/calmodulin dependent kinase II in the hearts of ORX rats were abolished after regular exercise. These results thus support the use of regular running as a cardioprotective alternative to testosterone replacement in hypogonadal conditions. PMID- 26272318 TI - New genetic and physiological factors for excessive erythrocytosis and Chronic Mountain Sickness. AB - In the last few years, genetic and functional studies have provided important insight on the pathophysiology of excessive erythrocytosis (EE), the main sign of Chronic Mountain Sickness (CMS). The recent finding of the association of the CMS phenotype with a single-nucleotide polymorphism (SNP) in the Sentrin-specific Protease 1 (SENP1) gene, and its differential expression pattern in Andean highlanders with and without CMS, has triggered large interest in high-altitude studies because of the potential role of its gene product in the control of erythropoiesis. The SENP1 gene encodes for a protease that regulates the function of hypoxia-relevant transcription factors such as Hypoxia-Inducible Factor (HIF) and GATA, and thus might have an erythropoietic regulatory role in CMS through the modulation of the expression of erythropoietin (Epo) or Epo receptors. The different physiological patterns in the Epo-EpoR system found among Andeans, even among highlanders with CMS, together with their different degrees of erythropoietic response, might indicate specific underlying genetic backgrounds, which in turn might reflect different levels of adaptation to lifelong high altitude hypoxia. This minireview discusses recent genetic findings potentially underlying EE and CMS, and their possible physiological mechanisms in Andean highlanders. PMID- 26272319 TI - Thrombospondin-2 deficiency in growing mice alters bone collagen ultrastructure and leads to a brittle bone phenotype. AB - Thrombospondin-2 (TSP2) is a matricellular protein component of the bone extracellular matrix. Long bones of adult TSP2-deficient mice have increased endosteal bone thickness due to expansion of the osteoblast progenitor cell pool, and these cells display deficits in osteoblastic potential. Here, we investigated the effects of TSP2 deficiency on whole bone geometric and mechanical properties in growing 6-wk-old male and female wild-type and TSP2-knockout (KO) mice. Microcomputed tomography and mechanical testing were conducted on femora and L2 vertebrae to assess morphology and whole bone mechanical properties. In a second series of experiments, femoral diaphyses were harvested from wild-type and TSP2 KO mice. Detergent-soluble type I collagen content was determined by Western blot of right femora. Total collagen content was determined by hydroxyproline analysis of left femora. In a third series of experiments, cortical bone was dissected from the anterior and posterior aspects of the femoral middiaphysis and imaged by transmission electron microscopy to visualize collagen fibrils. Microcomputed tomography revealed minimal structural effects of TSP2 deficiency. TSP2 deficiency imparted a brittle phenotype on cortical bone. Femoral tissue mineral density was not affected by TSP2 deficiency. Instead, transmission electron microscopy revealed less intensely stained collagen fibrils with altered morphology in the extracellular matrix assembled by osteoblasts on the anterior surface of TSP2-KO femora. Femoral diaphyseal bone displayed comparable amounts of total collagen, but the TSP2-KO bones had higher levels of detergent extractable type I collagen. Together, our data suggest that TSP2 is required for optimal collagen fibrillogenesis in bone and thereby contributes to normal skeletal tissue quality. PMID- 26272320 TI - Quadriceps exercise intolerance in patients with chronic obstructive pulmonary disease: the potential role of altered skeletal muscle mitochondrial respiration. AB - This study sought to determine if qualitative alterations in skeletal muscle mitochondrial respiration, associated with decreased mitochondrial efficiency, contribute to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). Using permeabilized muscle fibers from the vastus lateralis of 13 patients with COPD and 12 healthy controls, complex I (CI) and complex II (CII) driven State 3 mitochondrial respiration were measured separately (State 3:CI and State 3:CII) and in combination (State 3:CI+CII). State 2 respiration was also measured. Exercise tolerance was assessed by knee extensor exercise (KE) time to fatigue. Per milligram of muscle, State 3:CI+CII and State 3:CI were reduced in COPD (P < 0.05), while State 3:CII and State 2 were not different between groups. To determine if this altered pattern of respiration represented qualitative changes in mitochondrial function, respiration states were examined as percentages of peak respiration (State 3:CI+CII), which revealed altered contributions from State 3:CI (Con 83.7 +/- 3.4, COPD 72.1 +/- 2.4%Peak, P < 0.05) and State 3:CII (Con 64.9 +/- 3.2, COPD 79.5 +/- 3.0%Peak, P < 0.05) respiration, but not State 2 respiration in COPD. Importantly, a diminished contribution of CI-driven respiration relative to the metabolically less efficient CII-driven respiration (CI/CII) was also observed in COPD (Con 1.28 +/- 0.09, COPD 0.81 +/- 0.05, P < 0.05), which was related to exercise tolerance of the patients (r = 0.64, P < 0.05). Overall, this study indicates that COPD is associated with qualitative alterations in skeletal muscle mitochondria that affect the contribution of CI and CII-driven respiration, which potentially contributes to the exercise intolerance associated with this disease. PMID- 26272323 TI - Reorientation Dynamics of Chromophores in Photosensitive Polymers by Means of Coarse-Grained Modeling. AB - We study the photoisomerization of azobenzene chromophores embedded into a polymer matrix by using coarse-grained simulations. Two types of beads are considered: t- and c-beads, which are rich in trans and cis isomers, respectively. Simulations combine deterministic (molecular dynamics) and stochastic (random-type switching) parts. The ratio between the characteristic times for photoinduced reorientation and for orientation relaxation is tuned to be of the order found in experiments. The essential features of the phenomenon: 1) the existence of a stationary state, and 2) anisotropic distribution of the orientations of t-beads (orientation hole-burning effect), are reproduced. We study population dynamics of c-beads and the strength of the orientation hole burning, depending on the illumination wavelength and its intensity. The form of the reorientation potential of the mean force acting on the t-beads is analyzed and its use is validated. PMID- 26272322 TI - Macrophage migration inhibitory factor urinary excretion revisited - MIF a potent predictor of the immunosuppressive treatment outcomes in patients with proliferative primary glomerulonephritis. AB - BACKGROUND: Macrophage migration inhibitory factor (MIF) is a cytokine that shares many activities with other pro-inflammatory cytokines in primary glomerulonephritis (GN). This study assesses the influence of immunosuppressive treatment on serum and urine MIF in patients with proliferative (PGN) and non proliferative (NPGN) glomerulonephritis, and evaluates the potential of MIF in predicting outcomes. METHODS: Eighty-four patients (45 males and 39 females) with primary GN were included. Urinary excretion of MIF (ng/mg of urinary creatinine) was measured both pre- and post-treatment with combined steroids and cyclophosphamide. After a 12-month follow-up, the patients were retrospectively divided into four subgroups: responders of proliferative GN (R-PGN), non responders of proliferative GN (NR-PGN), responders of non-proliferative GN (R NPGN) and non-responders of non-proliferative GN (NR-NPGN). RESULTS: The median pre-treatment urinary MIF values were higher in PGN than in NPGN (3.6 versus 2.2; ANOVA P = 0.039). The highest pre-treatment urinary excretion of MIF was observed in NR-PGN (median 6.1), which was significantly higher than other subgroups (ANOVA P < 0.05). The treatment significantly reduced MIF urinary excretion only in R-PGN (P < 0.01). In NR-PGN, pre- (5.9 +/- 2.9 pg/mgCr) and post-treatment mean MIF excretion (4.9 +/- 2.3 pg/mgCr) exceeded the calculated cut off value (3.3 pg/mgCr). CONCLUSION: MIF urinary excretion appears to be a prognostic marker of therapy outcomes only in proliferative glomerulonephritis, in which lower urinary MIF may be linked with good prognosis, whereas a higher MIF urinary excretion value was a marker of unfavorable therapy outcomes. In Non-Responders, urinary MIF measurements may help to reconsider the choice of the immunosuppressive regimen at early stages of the treatment and act as an impulse to search for new therapeutic strategies. PMID- 26272321 TI - Sympathetic control of reflex cutaneous vasoconstriction in human aging. AB - This Synthesis highlights a series of recent studies that has systematically interrogated age-related deficits in cold-induced skin vasoconstriction. In response to cold stress, a reflex increase in sympathetic nervous system activity mediates reductions in skin blood flow. Reflex vasoconstriction during cold exposure is markedly impaired in aged skin, contributing to the relative inability of healthy older adults to maintain core temperature during mild cold stress in the absence of appropriate behavioral thermoregulation. This compromised reflex cutaneous vasoconstriction in healthy aging can occur as a result of functional deficits at multiple points along the efferent sympathetic reflex axis, including blunted sympathetic outflow directed to the skin vasculature, reduced presynaptic neurotransmitter synthesis and/or release, and altered end-organ responsiveness at several loci, in addition to potential alterations in afferent thermoreceptor function. Arguments have been made that the relative inability of aged skin to appropriately constrict is due to the aging cutaneous arterioles themselves, whereas other data point to the neural circuitry controlling those vessels. The argument presented herein provides strong evidence for impaired efferent sympathetic control of the peripheral cutaneous vasculature during whole body cold exposure as the primary mechanism responsible for attenuated vasoconstriction. PMID- 26272325 TI - Review of existing terrestrial bioaccumulation models and terrestrial bioaccumulation modeling needs for organic chemicals. AB - Protocols for terrestrial bioaccumulation assessments are far less-developed than for aquatic systems. This article reviews modeling approaches that can be used to assess the terrestrial bioaccumulation potential of commercial organic chemicals. Models exist for plant, invertebrate, mammal, and avian species and for entire terrestrial food webs, including some that consider spatial factors. Limitations and gaps in terrestrial bioaccumulation modeling include the lack of QSARs for biotransformation and dietary assimilation efficiencies for terrestrial species; the lack of models and QSARs for important terrestrial species such as insects, amphibians and reptiles; the lack of standardized testing protocols for plants with limited development of plant models; and the limited chemical domain of existing bioaccumulation models and QSARs (e.g., primarily applicable to nonionic organic chemicals). There is an urgent need for high-quality field data sets for validating models and assessing their performance. There is a need to improve coordination among laboratory, field, and modeling efforts on bioaccumulative substances in order to improve the state of the science for challenging substances. PMID- 26272324 TI - Can an antimicrobial stewardship program reduce length of stay of immune competent adult patients admitted to hospital with diagnosis of community acquired pneumonia? Study protocol for pragmatic controlled non-randomized clinical study. AB - BACKGROUND: Pneumonia is responsible for a large proportion of hospital admissions and antibiotic utilization. Physician adherence to evidence-based pneumonia management guidelines is poor. Antimicrobial stewardship programs (ASPs) are an effective intervention to mitigate against unwarranted variation from these guidelines. Despite this benefit, ASPs have not been shown to reduce the length of stay of hospitalized patients with pneumonia. In immune-competent adult patients admitted to a hospital ward with a diagnosis of community-acquired pneumonia, does a multi-faceted ASP utilizing prospective chart audit and feedback reduce the length of stay, compared with usual care, without increasing the risk of death or readmission 30 days after discharge from hospital? METHODS/DESIGN: Starting on 1 April 2013, all consecutive immune-competent adult patients (>18 years old) admitted to a hospital ward with a positive febrile respiratory illness screening questionnaire and a diagnosis of pneumonia by the attending physician will be eligible for inclusion in this non-randomized study. All eligible patients who fulfill the ASP review criteria will undergo a prospective chart audit, followed by an ASP recommendation provided to the attending physician. The attending physician is responsible for implementing or rejecting the ASP recommendation. This is a modified stepped-wedge design with a baseline data collection period of 3 months, followed by non-random sequential introduction of the ASP intervention on each of four hospital wards in a single community-based, academic-affiliated 339-bed acute-care hospital in Barrie, ON, Canada. The primary outcome measure is hospital length of stay; secondary outcome measures include days and duration of antibiotic therapy, and inadvertent adverse outcomes of 30 day post-discharge mortality and hospital readmission rates. Differences in outcome measures will be assessed using extended Cox regression analysis. Time to ASP intervention is included as a time-dependent covariate in the final model, to account for time-dependent bias. DISCUSSION: By designing a pragmatic clinical trial with unique design and analytic features, we not only expect to demonstrate the effectiveness of a real-world ASP, but also provide a model for program evaluation that can be used more broadly to improve patient safety and quality of care. TRIAL REGISTRATION: ClinicalTrials.gov NCT02264756 . PMID- 26272326 TI - Systematic review of school-based interventions to prevent smoking for girls. AB - BACKGROUND: The purpose of this review is to study the effect of school-based interventions on smoking prevention for girls. METHODS: We performed a systematic review of articles published since 1992 on school-based tobacco-control interventions in controlled trials for smoking prevention among children. We searched the databases of PubMed, Embase, Web of Science, The Cochrane Databases, CINAHL, Social Science Abstracts, and PsycInfo. Two reviewers independently assessed trials for inclusion and quality and extracted data. A pooled random effects estimate was estimated of the overall relative risk. RESULTS: Thirty seven trials were included, of which 16 trials with 24,210 girls were included in the pooled analysis. The overall pooled effect was a relative risk (RR) of 0.96 (95 % confidence interval (CI) 0.86-1.08; I (2)=75 %). One study in which a school-based intervention was combined with a mass media intervention showed more promising results compared to only school-based prevention, and four studies with girl-specific interventions, that could not be included in the pooled analysis, reported statistically significant benefits for attitudes and intentions about smoking and quit rates. CONCLUSIONS: There was no evidence that school-based smoking prevention programs have a significant effect on preventing adolescent girls from smoking. Combining school-based programs with mass media interventions, and developing girl-specific interventions, deserve additional study as potentially more effective interventions compared to school-based-only intervention programs. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42012002322. PMID- 26272327 TI - Physical fitness, serum relaxin and duration of gestation. AB - BACKGROUND: Women are recommended to perform regular exercise during pregnancy but the impact of physical fitness on duration of gestation and miscarriage is inconsistent. In addition, a dose-response relation between the amount of weekly exercise and increased risk of miscarriage in early pregnancy has been observed. Previous studies have mostly used an epidemiologic method. Larger studies using careful measurement of physical fitness are needed. Besides physical fitness, maternal circulating concentrations of the hormone relaxin have been associated with decreased duration of gestation. METHODS: A prospective cohort including 20 women with miscarriage and 460 women with spontaneous onset of labour, recruited from maternal health care centres in central Sweden, were examined in early pregnancy regarding estimated absolute peak oxygen uptake (VO2 peak, est.) by cycle ergometer test, and maternal circulating serum relaxin concentrations. RESULTS: Women with miscarriage displayed the highest level of absolute VO2 peak, est. (2.61 l/min) and the lowest serum relaxin concentrations (640 ng/l). Among women with spontaneous onset of labour, the mean absolute VO2 peak, est. increased successively from the lowest estimated oxygen uptake of 2.31 l/min among those with preterm birth (n = 28), to an oxygen uptake of 2.49 l/min among women with postterm birth (n = 31). An opposite trend was shown regarding serum relaxin concentrations from women with miscarriage to those with postterm birth. Serum relaxin concentrations, but not absolute VO2 peak, est. was significantly and independently associated with duration of gestation in women with miscarriages, and absolute VO2 peak, est., age and multiple pregnancy were independently associated with duration of gestation in women with spontaneous onset of labour. CONCLUSIONS: Physical fitness appears to be a protective factor of established pregnancies and not significantly involved in the risk of early miscarriage. Additional studies are needed to more clearly define the role of relaxin in miscarriage. PMID- 26272328 TI - Fast food increases postprandial cardiac workload in type 2 diabetes independent of pre-exercise: A pilot study. AB - BACKGROUND: Type 2 diabetes aggravates the postprandial metabolic effects of food, which increase cardiovascular risk. We investigated the acute effects of fast food on postprandial left ventricular (LV) function and the potential effects of pre-exercise in type 2 diabetes individuals. METHODS: We used a cross over study including 10 type 2 diabetes individuals (7 male and 3 females; 53.4 +/- 8.1 years; 28.3 +/- 3.8 kg/m(2); type 2 diabetes duration 3.1 +/- 1.8 years) and 10 controls (7 male and 3 females; 52.8 +/- 10.1 years; 28.5 +/- 4.2 kg/m(2)) performing high intensity interval exercise (HIIE; 40 min, 4 * 4 min intervals, 90-95% HRmax), moderate intensity exercise (MIE; 47 min, 70% HRmax) and no exercise (NE) in a random order 16-18 hours prior to fast-food ingestion. Baseline echocardiography, blood pressure and biochemical measurements were recorded prior to and 16-18 hours after exercise, and 30 minutes, 2 hours and 4 hours after fast food ingestion. RESULTS: LV diastolic (peak early diastolic tissue velocity, peak early diastolic filling velocity), and systolic workload (global strain rate, peak systolic tissue velocity, rate pressure product) increased after consumption of fast food in both groups. In contrast to controls, the type 2 diabetes group had prolonged elevations in resting heart rate and indications of prolonged elevations in diastolic workload (peak early diastolic tissue velocity) as well as reduced systolic blood pressure after fast food consumption. No significant modifications due to exercise in the postprandial phase were seen in any group. CONCLUSIONS: Our findings indicate that fast-food induces greater and sustained overall cardiac workload in type 2 diabetes individuals versus body mass index and age matched controls; exercise 16-18 hours pre-meal has no acute effects to the postprandial phase. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01991769. PMID- 26272329 TI - Phytochemical and Botanical Therapies for Rosacea: A Systematic Review. AB - Botanical and cosmeceutical therapies are commonly used to treat symptoms of rosacea such as facial erythema, papules/pustule counts, and telangiectasia. These products may contain plant extracts, phytochemicals, and herbal formulations. The objective of this study was to review clinical studies evaluating the use of botanical agents for the treatment of rosacea. MEDLINE and Embase databases were searched for clinical studies evaluating botanical therapies for rosacea. Major results were summarized, and study methodology was analyzed. Several botanical therapies may be promising for rosacea symptoms, but few studies are methodologically rigorous. Several plant extract and phytochemicals effectively improved facial erythema and papule/pustule counts caused by rosacea. Many studies are not methodologically rigorous. Further research is critical, as many botanicals have been evaluated in only one study. Botanical agents may reduce facial erythema and effectively improve papule/pustule counts associated with rosacea. Although promising, further research in the area is imperative. PMID- 26272330 TI - Exploratory effects of a strong CYP3A inhibitor (ketoconazole), a strong CYP3A inducer (rifampicin), and concomitant ethanol on piragliatin pharmacokinetics and pharmacodynamics in type 2 diabetic patients. AB - Piragliatin is a CYP3A substrate; its inactive metabolite M4, formed through cytosolic reductase, is reversibly metabolized back to piragliatin through CYP3A. The impact of concomitant CYP3A modifiers thus cannot be predicted. Drinking alcohol under fasting conditions is associated with a recognized glucose-lowering effect, which might be synergistic with piragliatin's hypoglycemic effect. Two exploratory studies were conducted to examine these potential interactions in type 2 diabetes (T2D) patients: 16 completed an open-label, sequential 2-way crossover, 2-arm (randomized to ketoconazole and rifampicin) CYP3A study; another 18 participated in a double-blind, placebo-controlled, randomized 3-way crossover ethanol study. Administration of piragliatin (100-mg single dose) resulted in a 32% Cmax and 44% area under the curve (AUCinfinity ) increase in piragliatin exposure without affecting glucose AUC0-6h following ketoconazole (400 mg QD * 5 days); 30% Cmax and 72% AUCinfinity decrease in piragliatin exposure with a 13% increase in glucose AUC0-6h following rifampicin (600 mg QD * 5 days); and, unexpectedly, a 32% Cmax and 23% AUC0-6h decrease (no change in AUCinfinity ) in piragliatin exposure with a 13% increase in glucose AUC0-6h following alcohol (40 g single dose). In conclusion, a strong CYP3A modifier or concomitant alcohol could lead to a change in exposure to piragliatin with a potential alteration in glucose-lowering effect. PMID- 26272331 TI - Integrated DNA walking system to characterize a broad spectrum of GMOs in food/feed matrices. AB - BACKGROUND: In order to provide a system fully integrated with qPCR screening, usually used in GMO routine analysis, as well as being able to detect, characterize and identify a broad spectrum of GMOs in food/feed matrices, two bidirectional DNA walking methods targeting p35S or tNOS, the most common transgenic elements found in GM crops, were developed. These newly developed DNA walking methods are completing the previously implemented DNA walking method targeting the t35S pCAMBIA element. METHODS: Food/feed matrices containing transgenic crops (Bt rice or MON863 maize) were analysed using the integrated DNA walking system. RESULTS: First, the newly developed DNA walking methods, anchored on the sequences used for the p35S or tNOS qPCR screening, were tested on Bt rice that contains these two transgenic elements. Second, the methods were assessed on a maize sample containing a low amount of the GM MON863 event, representing a more complex matrix in terms of genome size and sensitivity. Finally, to illustrate its applicability in GMO routine analysis by enforcement laboratories, the entire workflow of the integrated strategy, including qPCR screening to detect the potential presence of GMOs and the subsequent DNA walking methods to characterize and identify the detected GMOs, was applied on a GeMMA Scheme Proficiency Test matrix. Via the characterization of the transgene flanking region between the transgenic cassette and the plant genome as well as of a part of the transgenic cassette, the presence of GMOs was properly confirmed or infirmed in all tested samples. CONCLUSION: Due to their simple procedure and their short time-frame to get results, the developed DNA walking methods proposed here can be easily implemented in GMO routine analysis by the enforcement laboratories. In providing crucial information about the transgene flanking regions and/or the transgenic cassettes, this DNA walking strategy is a key molecular tool to prove the presence of GMOs in any given food/feed matrix. PMID- 26272332 TI - Development of polymorphic microsatellite loci for conservation genetic studies of the coral reef fish Centropyge bicolor. AB - A total of 23 novel polymorphic microsatellite marker loci were developed for the angelfish Centropyge bicolor through 454 sequencing, and further tested on two spatially separated populations (90 individuals each) from Kimbe Bay in Papua New Guinea. The mean +/- s.e. number of alleles per locus was 14.65 +/- 1.05, and mean +/- s.e. observed (HO ) and expected (HE ) heterozygosity frequencies were 0.676 +/- 0.021 and 0.749 +/- 0.018, respectively. The markers reported here constitute the first specific set for this genus and will be useful for future conservation genetic studies in the Indo-Pacific region. PMID- 26272333 TI - Relativistic state-specific multireference perturbation theory incorporating improved virtual orbitals: Application to the ground state single-bond dissociation. AB - Using four-component (4c) relativistic spinors, we present a computationally economical relativistic ab initio method for molecular systems employing our recently proposed second-order state-specific multireference perturbation theory (SSMRPT) incorporating the improved virtual orbital-complete active space configuration interaction (IVO-CASCI) reference wavefunction. The resulting method, 4c-IVO-SSMRPT [calculate one state at a time] is tested in pilot calculations on the homonuclear dimers including Li(2), Na(2), K(2), Rb(2), F(2), Cl(2), and Br(2) through the computations of the ground state potential energy curves (PECs). As SSMRPT curbs intruder effects, 4c-IVO-SSMRPT is numerically stable. To our knowledge, the SSMRPT in the 4c relativistic framework has not been explored in the past. Selective spectroscopic constants that are closely related to the correct shape and accuracy of the energy surfaces have been extracted from the computed PECs. For the halogen molecules, a relativistic destabilization of the bond has been found. Relativistic and electron correlation effects need to be incorporated to get reliable estimates. Our results are in good accordance with reference theoretical and experimental data which manifests the computational accuracy and efficiency of the new 4c-IVO-SSMRPT method. The method opens for an improved description of MR systems containing heavy elements. The inexpensiveness of IVO-CASCI makes 4c-IVO-SSMRPT method promising for studies on large systems of heavy elements. PMID- 26272335 TI - Radiographical measurements for distal intra-articular fractures of the radius using plain radiographs and cone beam computed tomography images. AB - OBJECTIVE: Operative treatment of an intra-articular distal radius fracture is one of the most common procedures in orthopedic and hand surgery. The intra- and interobserver agreement of common radiographical measurements of these fractures using cone beam computed tomography (CBCT) and plain radiographs were evaluated. MATERIALS AND METHODS: Thirty-seven patients undergoing open reduction and volar fixation for a distal radius fracture were studied. Two radiologists analyzed the preoperative radiographs and CBCT images. Agreement of the measurements was subjected to intra-class correlation coefficient and the Bland-Altman analyses. RESULTS: Plain radiographs provided a slightly poorer level of agreement. For fracture diastasis, excellent intraobserver agreement was achieved for radiographs and good or excellent agreement for CBCT, compared to poor interobserver agreement (ICC 0.334) for radiographs and good interobserver agreement (ICC 0.621) for CBCT images. The Bland-Altman analyses indicated a small mean difference between the measurements but rather large variation using both imaging methods, especially in angular measurements. CONCLUSIONS: For most of the measurements, radiographs do well, and may be used in clinical practice. Two different measurements by the same reader or by two different readers can lead to different decisions, and therefore a standardization of the measurements is imperative. More detailed analysis of articular surface needs cross-sectional imaging modalities. PMID- 26272336 TI - Prognostic significance of morphological growth patterns and mitotic index of epithelioid malignant peritoneal mesothelioma. AB - AIMS: The prognostic significance of histological subtyping of epithelioid pleural mesotheliomas has been recently reported, but similar data are lacking for peritoneal mesotheliomas. The aim of this study was to investigate possible relationships between histological growth patterns of epithelioid peritoneal mesotheliomas, clinicopathological features, and patient outcome. METHODS AND RESULTS: Eighty-four cases of chemotherapy-naive epithelioid peritoneal mesothelioma were classified into tubulopapillary, micropapillary, papillary, tubular, solid and trabecular growth patterns. Pathological features such as depth of invasion, lymphocytic host response, mitotic count, nuclear grade, lymphovascular invasion, lymph node metastasis and stromal desmoplasia were analysed. The most common histological patterns were solid (n = 37, 44%), tubulopapillary (n = 24, 29%), and micropapillary (n = 11, 13%). The overall median survival was 36 months. Patients with solid mesothelioma had shorter overall survival (median, 29 months) than patients with tubulopapillary and micropapillary growth patterns (median, 51 and 53 months, respectively; P = 0.053). A high mitotic index (>5 in 50 high-power fields) was found to be associated with poor survival (P < 0.03). A moderate to severe lymphocytic host response was associated with longer median survival (P = 0.13). CONCLUSIONS: Our study highlights the prognostic importance of the solid growth pattern among diffuse epithelioid peritoneal mesotheliomas, and reaffirms mitotic index as a predictor of overall survival. PMID- 26272334 TI - Drug carrier interaction with blood: a critical aspect for high-efficient vascular-targeted drug delivery systems. AB - Vascular wall endothelial cells control several physiological processes and are implicated in many diseases, making them an attractive candidate for drug targeting. Vascular-targeted drug carriers (VTCs) offer potential for reduced side effects and improved therapeutic efficacy, however, only limited therapeutic success has been achieved to date. This is perhaps due to complex interactions of VTCs with blood components, which dictate VTC transport and adhesion to endothelial cells. This review focuses on VTC interaction with blood as well as novel 'bio-inspired' designs to mimic and exploit features of blood in VTC development. Advanced approaches for enhancing VTCs are discussed along with applications in regenerative medicine, an area of massive potential growth and expansion of VTC utility in the near future. PMID- 26272339 TI - Two phosphonium ionic liquids with high Li(+) transport number. AB - This work presents the physicochemical characterization of two ionic liquids (ILs) with small phosphonium cations, triethylpenthylphosphonium bis(trifluoromethanesulfonyl)imide ([P2225][Tf2N]) and (2 methoxyethyl)trimethylphosphonium bis(trifluoromethanesulfonyl)imide ([P222(201)][Tf2N]), and their mixtures with Li(+). Properties such as the electrochemical window, density, viscosity and ionic conductivity are presented. The diffusion coefficient was obtained using two different techniques, PGSE-NMR and Li electrodeposition with microelectrodes. In addition, the Li(+) transport number was calculated using the PGSE-NMR technique and an electrochemical approach. The use of these three techniques showed that the PGSE-NMR technique underestimates the diffusion coefficient for charged species. The Li(+) transport number was found to be as high as 0.54. Raman spectroscopy and molecular dynamics simulations were used to evaluate the short-range structure of the liquids. These experiments suggested that the interaction between the Li(+) and the Tf2N(-) anion is similar to that seen with other ILs containing the same anion. However, the MD simulations also showed that the Li(+) ions interact differently with the cation containing an alkyl ether chain. The results found in this work suggest that these Li(+) mixtures have promising potential to be applied as electrolytes in batteries. PMID- 26272337 TI - Dexamethasone-dependent modulation of cyclic GMP synthesis in podocytes. AB - Podocytes may be direct target for glucocorticoid therapy in glomerular proteinuric disease. Permeability of podocytes largely depends on their capacity to migrate which involves the contractile apparatus in their foot processes. In this study, we examined the effect of synthetic glucocorticoid dexamethasone (DEX) on the ability of podocytes to produce cyclic guanosine monophosphate (cGMP) in the presence of vasoactive factors, atrial natriuretic peptide (ANP), nitric oxide (NO), and angiotensin II (Ang II). We investigated also the effects of cGMP and DEX on podocyte motility. Primary rat podocytes and immortalized mouse podocytes were pretreated with 1 uM DEX for 4 or 24 h. Glomerular hypertension was mimicked by subjecting the cells to mechanical stress. Total and subcellular cGMP levels were determined in podocytes incubated with 0.1 uM ANP, 1 uM S-nitroso-N-acetyl penicillamine (SNAP), and 1 uM Ang II. Cell motility was estimated by a wound-healing assay. The ANP-dependent production of cGMP increased after 4 h exposition to DEX, but was attenuated after 24 h. Adversely, a 24-h pretreatment with DEX augmented the NO-dependent cGMP synthesis. Ang II suppressed the ANP-dependent cGMP production and the effect was enhanced by DEX in mechanical stress conditions. Mechanical stress reduced total cGMP production in the presence of all stimulators, whereas extracellular to total cGMP ratio increased. 8-Br cGMP enhanced podocyte migration which was accompanied by F-actin disassembly. In the presence of DEX these effects were prevented. We conclude that DEX modulates the production of cGMP in podocytes stimulated with vasoactive factors such as Ang II, ANP, and NO, and the effect is time-dependent. cGMP increases podocyte motility, which is prevented by DEX. This mechanism may account for the antiproteinuric effect of glucocorticoids. PMID- 26272338 TI - A novel adipokine C1q/TNF-related protein 3 is expressed in developing skeletal muscle and controls myoblast proliferation and differentiation. AB - Several hormones and growth factors, including adipokines, play important roles during muscle development and regeneration. CTRP3, a paralog of adiponectin, is a member of the C1q and tumor necrosis factor-related protein (CTRP) superfamily. CTRP3 is a novel adipokine previously reported to reduce glucose output in hepatocytes and lower glucose levels in mice models. In the present study, we provide the first evidence for a physiological role of the CTRP3 in myogenesis using C2C12 myoblasts. CTRP3 was expressed in developing skeletal muscle tissues, and the expression level of CTRP3 was increased during myogenic differentiation of C2C12 cells. Recombinant CTRP3 (rCTRP3) promoted the proliferation of undifferentiated C2C12 myoblasts and this response required activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. In contrary, rCTRP3 inhibited myogenic differentiation and fusion of C2C12 cells by suppressing the expression of myogenic marker genes (myogenin and myosin heavy chain). CTRP3 mRNA expression was increased in C2C12 myoblasts treated with transforming growth factor-beta3 (TGF-beta3), suggesting that TGF-beta3 is one of the extracellular factors regulating CTRP3 expression during myogenesis. These results indicate a novel physiological role for CTRP3 during skeletal myogenesis. PMID- 26272342 TI - Judgement days: moral attitudes in the wake of local disasters. AB - The deaths and destruction stemming from a disaster are traumatic enough to implicate victims' beliefs not only about disasters themselves but also about other social and political concerns. In particular, disasters are associated with the scapegoating of out-groups, suggesting that even deep-rooted moral concerns may shift, at least temporarily, after disasters. This study uses exposure to local natural disaster fatalities to examine moral judgements regarding gays in United States surveys from 1984-98. Survey respondents whose county has suffered a disaster feel appreciably more negatively towards gays, even though most of the disasters in this data set are relatively small and local. The increased antipathy towards gays dissipates within months, and is most marked among those who had, before the disaster, considered themselves more religious. These results raise the possibility that some groups, especially those already marginalised by society, may suffer in a backlash in the wake of a natural disaster. PMID- 26272341 TI - Similar Adiponectin Levels in Obese Normotensive and Obese Hypertensive Men and No Vasorelaxant Effect of Adiponectin on Human Arteries. AB - Obesity is a strong risk factor for hypertension, but the mechanism linking obesity to hypertension is not fully elucidated. In obesity, circulating concentrations of adiponectin are decreased and hypoadiponectinaemia has in some but not all studies been associated with increased risk of hypertension. Due to this inconsistency, we decided to study adiponectin from two aspects in a cross sectional in vivo study and in an experimental in vitro study. In the cross sectional study, 103 men with body mass index (BMI) >= 30.0 kg/m(2) were studied; 63 had 24-hr ambulatory blood pressure (ABP) >= 130/80 mmHg (ObeseHT) and 40 had 24-hr ABP < 130/80 mmHg (ObeseNT). As controls, we studied 27 men with BMI between 20.0 and 24.9 kg/m(2) and 24-hr ABP < 130/80 mmHg (LeanNT). Serum concentrations of adiponectin and body composition using dual-energy X-ray absorptiometry scanning were determined. In vitro, the direct vasomotor response of adiponectin was tested on subcutaneous resistance arteries from human abdominal adipose tissue. The two obese groups had lower adiponectin concentrations compared with LeanNT (p < 0.01) [median (interquartile range)]: ObeseHT 6.5 (5.1-8.3) mg/L; ObeseNT 6.6 (5.2-7.8) mg/L; and LeanNT 9.4 (6.7-12.4) mg/L, with no significant difference in adiponectin concentrations (or body composition) between ObeseHT and ObeseNT (p = 0.67). In vitro, adiponectin did not have any direct vasodilatory effect and adiponectin did not affect angiotensin II-stimulated vasoconstriction. In conclusion, obese hypertensive men have similar serum concentrations of adiponectin as obese normotensive men. In combination with the in vitro data, these findings question a pathogenic role of adiponectin in human hypertension. PMID- 26272340 TI - Polymorphism in COMT is associated with IgG3 subclass level and susceptibility to infection in patients with chronic fatigue syndrome. AB - BACKGROUND: Chronic fatigue syndrome (CFS) is considered as a neuroimmunological disease but the etiology and pathophysiology is poorly understood. Patients suffer from sustained exhaustion, cognitive impairment and an increased sensitivity to pain and sensory stimuli. A subset of patients has frequent respiratory tract infections (RRTI). Dysregulation of the sympathetic nervous system and an association with genetic variations in the catechol-O methyltransferase (COMT) and glucocorticoid receptor genes influencing sympathetic and glucocorticoid metabolism were reported in CFS. Here, we analyzed the prevalence of SNPs of COMT and glucocorticoid receptor-associated genes in CFS patients and correlated them to immunoglobulin levels and susceptibility to RRTI. METHODS: We analyzed blood cells of 74 CFS patients and 76 healthy controls for polymorphisms in COMT, FKBP5 and CRHR1 by allelic discrimination PCR. Serum immunoglobulins were determined by immunoturbidimetric technique, cortisol levels by ECLIA. RESULTS: Contrary to previous reports, we found no difference between CFS patients and healthy controls in the prevalence of SNPs for COMT, FKBP5 and CRHR1. In patients with the Met/Met variant of COMT rs4680 we observed enhanced cortisol levels providing evidence for its functional relevance. Both enhanced IgE and diminished IgG3 levels and an increased susceptibility to RRTI were observed in CFS patients with the Met/Met variant. Such an association was not observed in 68 non-CFS patients with RRTI. CONCLUSION: Our results indicate a relationship of COMT polymorphism rs4680 with immune dysregulation in CFS providing a potential link for the association between stress and infection susceptibility in CFS. PMID- 26272343 TI - Effect of colestilan on serum phosphorus in dialysis patients: A meta-analysis of the literature. AB - AIM: To evaluate the efficacy and safety of colestilan as a phosphorus binder in dialysis patients, we performed a meta-analysis of randomized controlled trials. METHODS: We retrieved studies that compared colestilan with placebo in the treatment of dialysis patients from Medline, EMBASE, the Cochrane Library and conference proceedings. RESULTS: Four studies were included. The treatment durations ranged from 2 to 12 weeks, median 7.5 weeks. Compared with placebo group, colestilan significantly decreased serum phosphorus (WMD, -0.22 mmol/L; 95% CI, -0.33 to -0.12, P < 0.0001), calcium phosphorus product (WMD, -0.70 mmol(2) /L(2) ; 95% CI, -1.06 to -0.35, P = 0.0001), intact PTH (WMD, -5.37 pmol/L; 95% CI, -8.38 to -2.36, P = 0.0005) and LDL cholesterol (WMD, -0.78 mmol/L; 95% CI, -0.85 to -0.71, P < 0.00001). There was no significant difference in serum calcium between the two groups. Colestilan therapy increased gastrointestinal complaints significantly (OR = 4.07, 95% CI: 3.06-6.53, P < 0.00001). Sensitivity analysis was performed by excluding studies with Jadad score of three or 3 g/day colestilan, the results did not change. CONCLUSIONS: Short-term administration of colestilan is effective for the treatment of hyperphosphataemia in dialysis patients. Long-term effectiveness and safety needs to be evaluated. PMID- 26272344 TI - Highly antiplasmodial non-natural oxidative products of dioncophylline A: synthesis, absolute configuration, and conformational stability. AB - Four new compounds, the monomeric dioncotetralones A (6 a) and B (6 b) and the dimeric compounds jozimine A3 (7) and jozimine A4 (9), were semi-synthesized from the natural product dioncophylline A (4) and its 5'-O-demethylated derivative (5), respectively, under phenol oxidative reaction conditions. Dioncotetralones A (6 a) and B (6 b) possess an unprecedented Z-configured double bond, in contrast to the classic biaryl axis that is present in the precursor dioncophylline A (4), and an additional stereogenic center at the C2' atom was generated due to the dearomatization. The resulting steric repulsion forced the expected planar double bond into a helical distorted conformation. The homocoupling of 5 yielded compounds 7 and 9, the latter of which is the first sp(3) -sp(2) coupled product of a monomeric naphthylisoquinoline with a reduced one and, thus, contains a newly generated stereogenic center. The full stereostructures of 6 a, 6 b, 7, and 9 were successfully elucidated by the interplay of spectroscopic methods (1D/2D NMR and electronic circular-dichroism spectroscopy) in combination with quantum chemical calculations. In addition, compounds 6 a and 7 exhibited high antiplasmodial activities with excellent half-maximal inhibitory concentration values. PMID- 26272346 TI - CoDiab-VD: protocol of a prospective population-based cohort study on diabetes care in Switzerland. AB - BACKGROUND: Diabetes represents an increasing health burden worldwide. In 2010, the Public Health Department of the canton of Vaud (Switzerland) launched a regional diabetes programme entitled "Programme cantonal Diabete" (PcD), with the objectives to both decrease the incidence of diabetes and improve care for patients with diabetes. The cohort entitled CoDiab-VD emerged from that programme. It specifically aimed at following quality of diabetes care over time, at evaluating the coverage of the PcD within this canton and at assessing the impact of the PcD on care of patients with diabetes. METHODS/DESIGN: The cohort CoDiab-VD is a prospective population-based cohort study. Patients with diabetes were recruited in two waves (autumn 2011--summer 2012) through community pharmacies. Eligible participants were non-institutionalised adult patients (>= 18 years) with diabetes diagnosed for at least one year, residing in the canton of Vaud and coming to a participating pharmacy with a diabetes-related prescription. Women with gestational diabetes, people with obvious cognitive impairment or insufficient command of French were not eligible. Self-reported data collected, included the following primary outcomes: processes-of-care indicators (annual checks) and outcomes of care such as HbA1C, (health-related) quality of life measures (Short Form-12 Health Survey--SF-12, Audit of Diabetes Dependent Quality of Life 19--ADDQoL) and Patient Assessment of Chronic Illness Care (PACIC). Data on diabetes, health status, healthcare utilisation, health behaviour, self-management activities and support, knowledge of, or participation to, campaigns/activities proposed by the PcD, and socio-demographics were also obtained. For consenting participants, physicians provided few additional pieces of information about processes and laboratory results. Participants will be followed once a year, via a mailed self-report questionnaire. The core of the follow-up questionnaires will be similar to the baseline one, with the addition of thematic modules adapting to the development of the PcD. Physicians will be contacted every 2 years. DISCUSSION: CoDiab-VD will allow obtaining a broad picture of the care of patients with diabetes, as well as their needs regarding their chronic condition. The data will be used to evaluate the PcD and help prioritise targeted actions. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, identifier NCT01902043, July 9, 2013. PMID- 26272347 TI - Relationship between fragmented QRS and paradoxical septal motion in coronary artery bypass graft patients. AB - OBJECTIVE: Paradoxical septal motion (PSM) can cause confusion in the assessment of ventricular function with scintigraphy even in the absence of ventricular septal damage and ischemia. Fragmented QRS (fQRS) is associated with various cardiac disorders. In this study, we aimed to determine the correlation between paradoxical septal motion and fQRS after coronary artery bypass grafting (CABG). METHODS: We retrospectively reviewed the hospital records showing scintigraphic images and electrocardiograms (ECG) of the patients who had undergone CABG. The patients were classified based on the evaluation of motion and thickening of the septal wall. The patients with regular thickening of the septal wall and abnormal motion were classified as PSM (+) group. The patients with normal motion and thickening of the septal wall were classified as PSM (-) group. fQRS complexes are defined as various RSR patterns either with or without Q-waves on a 12-lead resting ECG. RESULTS: PSM was found to be more common in fQRS patients (p < 0.001). PSM was seen in 91.4 % of cases with fQRS and in 79.8 % of cases without fQRS. No significant differences were found in the phase analysis parameters. A correlation was found between septal wall motion values and the presence of fQRS (r = 0.197, p = 0.012). CONCLUSION: fQRS was associated with PSM. fQRS may cause PSM in patients with CABG without left bundle branch block due to a conduction defect. PSM and fQRS are predictive of cardiac mortality. Patients diagnosed with PSM and fQRS, should be monitored closely. PMID- 26272345 TI - Cell painting with an engineered EPCR to augment the protein C system. AB - The protein C (PC) system conveys beneficial anticoagulant and cytoprotective effects in numerous in vivo disease models. The endothelial protein C receptor (EPCR) plays a central role in these pathways as cofactor for PC activation and by enhancing activated protein C (APC)-mediated protease-activated receptor (PAR) activation. During inflammatory disease, expression of EPCR on cell membranes is often diminished thereby limiting PC activation and APC's effects on cells. Here a caveolae-targeting glycosylphosphatidylinositol (GPI)-anchored EPCR (EPCR-GPI) was engineered to restore EPCR's bioavailability via "cell painting." The painting efficiency of EPCR-GPI on EPCR-depleted endothelial cells was time- and dose-dependent. The EPCR-GPI bioavailability after painting was long lasting since EPCR surface levels reached 400 % of wild-type cells after 2 hours and remained > 200 % for 24 hours. EPCR-GPI painting conveyed APC binding to EPCR depleted endothelial cells where EPCR was lost due to shedding or shRNA. EPCR painting normalised PC activation on EPCR-depleted cells indicating that EPCR-GPI is functional active on painted cells. Caveolin-1 lipid rafts were enriched in EPCR after painting due to the GPI-anchor targeting caveolae. Accordingly, EPCR painting supported PAR1 and PAR3 cleavage by APC and augmented PAR1-dependent Akt phosphorylation by APC. Thus, EPCR-GPI painting achieved physiological relevant surface levels on endothelial cells, restored APC binding to EPCR-depleted cells, supported PC activation, and enhanced APC-mediated PAR cleavage and cytoprotective signalling. Therefore, EPCR-GPI provides a novel tool to restore the bioavailability and functionality of EPCR on EPCR- depleted and -deficient cells. PMID- 26272348 TI - Comparison of ultrasonography features and malignancy rate of toxic and nontoxic autonomous nodules: a preliminary study. AB - OBJECTIVE: When a scintigraphically autonomous nodule does not produce thyroid hormones enough to suppress serum thyrotrophin, it is generally defined as nontoxic autonomous nodule. In this study, we aimed to compare clinical and ultrasonographical (US) features and cytological and histopathological results of toxic and nontoxic autonomous nodules. METHODS: Patients who underwent thyroidectomy and were evaluated with technetium-99m-pertechnetate scintigraphy preoperatively in our institution between May 2008 and December 2014 were identified from medical records. Among these, treatment naive patients with scintigraphically autonomous thyroid nodules were chosen and classified into toxic (hyperthyroid) and nontoxic (euthyroid) groups. The demographic data, preoperative US features of the nodules, fine needle aspiration biopsy and histopathological results were analyzed. RESULTS: There were 170 (89.0%) patients with toxic and 21 (11.0%) patients with nontoxic autonomous nodules. A total of 258 scintigraphically autonomous nodules were analyzed among which 227 were clinically functional (toxic) and 31 were clinically euthyroid (nontoxic). Echogenity, texture, marginal irregularity, presence of halo and macrocalcification were similar in toxic and nontoxic autonomous nodules. Toxic autonomous nodules were significantly bigger and had a significantly higher rate of microcalcification compared to nontoxic ones (p = 0.001 and p = 0.025, respectively). There was no significant difference in terms of cytological diagnosis between toxic and nontoxic autonomous nodules (p = 0.052). Atypia of undetermined significance/follicular lesion of undetermined significance cytology was significantly higher in nontoxic group (p = 0.01). 20 (8.8%) of 227 toxic and 2 (6.5%) of 31 nontoxic autonomous nodules were malignant (p = 0.59). Considering all nodules regardless of the thyroid function, 8.5% of autonomous nodules was malignant. CONCLUSION: US features and malignancy potential of nontoxic autonomous nodules resemble toxic autonomous nodules. Lower diameter suggests that they can represent a preliminary stage of toxic ones and have potential of toxicity when get bigger in size. There is still a considerable risk of malignancy risk in autonomous nodules whether toxic or not. PMID- 26272350 TI - N-Heterocyclic Carbene-Palladium(II)-1-Methylimidazole Complex Catalyzed Direct C H Bond Arylation of Benzo[b]furans with Aryl Chlorides. AB - The first example of sole direct C-H bond arylation of benzo[b]furans with aryl chlorides was achieved catalyzed by a well-defined NHC-Pd(II)-Im complex. Under the suitable conditions, all reactions involving kinds of benzo[b]furans and (hetero)aryl chlorides proceeded well to give the desired C2-arylated benzo[b]furans in sole regioselectivity in acceptable to high yields, providing an efficient and economic pathway for the direct C2-H bond arylation of benzo[b]furans. PMID- 26272351 TI - Iodine status of adults in Taiwan 2005-2008, 5 years after the cessation of mandatory salt iodization. AB - BACKGROUND/PURPOSE: Iodine deficiency causes a broad spectrum of disorders across all ages. Mandatory salt iodization in Taiwan successfully reduced the goiter rate from 21.6% to 4.3% in schoolchildren surveyed in 1971. The program continued until 2003 when salt iodization was changed from mandatory to voluntary. The purpose of this study was to investigate the iodine status of Taiwanese individuals after the change in the iodine policy. METHODS: Urinary iodine (UI) was measured in samples from adults in the Nutrition and Health Survey in Taiwan 2005-2008. RESULTS: The median UI level was 100 MUg/L, and the percentage of populations with UI levels below 100 MUg/L and 50 MUg/L was 50.1% and 15.1%, respectively, indicating that the iodine status was borderline adequate. Men had a higher UI level than women (102 MUg/L vs. 98 MUg/L, p = 0.003), and older individuals (age > 60 years) had a lower UI level than younger people, particularly in women. The iodine status of the population < 50 years was sufficient, but it was insufficient in older groups. Mild iodine insufficiency was noted in all areas of Taiwan except the Southern area and Penghu islands, with the lowest UI level of 79 MUg/L in the Mountain area. Although the UI level of women of childbearing age (19-44 years) was 103 MUg/L, there may be a risk of iodine deficiency during pregnancy. CONCLUSION: The iodine nutrition of the Taiwanese population in 2005-2008 was borderline adequate, with insufficiency in some subgroups. Further monitoring of the iodine status is necessary. PMID- 26272349 TI - Heterologous production of a feruloyl esterase from Pleurotus sapidus synthesizing feruloyl-saccharide esters. AB - The feruloyl esterase (FAE) gene EST1 from the basidiomycete Pleurotus sapidus was heterologously expressed in Escherichia coli and Pichia pastoris. Catalytically active recombinant Est1 was secreted using P. pastoris as a host. For expression in P. pastoris, the expression vector pPIC9K was applied. The EST1 gene was cloned with an N-terminal alpha-mating factor pre-pro sequence and expressed under the control of a methanol inducible alcohol oxidase 1 promotor. Est1 was purified to homogeneity using ion exchange and hydrophobic interaction chromatography. The recombinant Est1 showed optima at pH 5.0 and 50 degrees C, and released ferulic acid from saccharide esters and from the natural substrate destarched wheat bran. Substrate specificity profile and descriptor-based analysis demonstrated unique properties, showing that Est1 did not fit into the current FAE classification model. Transferuloylation synthesis of feruloyl saccharide esters was proven for mono- and disaccharides. PMID- 26272352 TI - When and how do prosthetic hips fail after total hip arthroplasties?-A retrospective study. AB - BACKGROUND/PURPOSE: Understanding failure modes, time to revision, and vulnerable components in revision hips could help reduce the risk of revision surgeries. Our aim was to investigate the association between the index diagnosis and the failure mode in patients undergoing revision surgeries. METHODS: A total of 402 patients who underwent a first revision surgery in a single hospital between 2000 and 2012 were recruited in a retrospective study. Multiple logistic regression analysis was used to evaluate the association of the index diagnosis of the primary total hip arthroplasty and short-term failure, as well as specific failure mode that occurred early, while controlling for sex, age, and the type of prosthesis. RESULTS: The mean time to revision due to all failure modes was 9.48 (standard deviation = 6.08) years. Defining short-term failure as a time to revision <5 years after total hip arthroplasty, the primary failure mode was infection (32.4%), followed by loosening (25.7%) and instability (17.1%). In multivariate analysis, as compared to osteonecrosis, patients with index diagnosis as infection was significantly associated with revision due to infection (odds ratio = 9.69, p = 0.013). In addition, osteoarthritis increased the odds of loosening (odds ratio = 4.18, p = 0.012). In contrast to studies in the United States and Europe, acetabular component revisions were the most common type found in our study. CONCLUSION: This study demonstrates that, compared with patients with osteonecrosis, patients with infection and osteoarthritis had higher odds of revision due to infection and loosening, respectively. Further studies are needed to examine the cause-effect relationship between index diagnosis and mode of failure. PMID- 26272353 TI - How important are autonomy and work setting to nurse practitioners' job satisfaction? AB - PURPOSE: Nurse practitioners (NPs) have reported aspects of their jobs that they are more and less satisfied with. However, few studies have examined the factors that predict overall job satisfaction. This study uses a large national sample to examine the extent to which autonomy and work setting predict job satisfaction. DATA SOURCES: The 2012 National Sample Survey of Nurse Practitioners (n = 8311) was used to examine bivariate and multivariate relationships between work setting and three autonomy variables (independent billing practices, having one's NP skills fully utilized, and relationship with physician), and job satisfaction. CONCLUSIONS: NPs working in primary care reported the highest levels of autonomy across all three autonomy measures, while those working in hospital surgical settings reported the lowest levels. Autonomy, specifically feeling one's NP skills were fully utilized, was the factor most predictive of satisfaction. In multivariate analyses, those who strongly agreed their skills were being fully utilized had satisfaction scores almost one point higher than those who strongly disagreed. Work setting was only marginally related to job satisfaction. IMPLICATIONS FOR PRACTICE: In order to attract and retain NPs in the future, healthcare organizations should ensure that NPs' skills are being fully utilized. PMID- 26272354 TI - Inhibition of inflammation by astaxanthin alleviates cognition deficits in diabetic mice. AB - Neurons in the hippocampal and cortical functional regions are more susceptible to damage induced by hyperglycemia, which can result in severe spatial learning and memory impairment. Neuroprotection ameliorates cognitive impairment induced by hyperglycemia in diabetic encephalopathy (DE). Astaxanthin has been widely studied in diabetes mellitus and diabetic complications due to its hypoglycemic, antioxidant and anti-apoptotic effects. However, whether astaxanthin can alleviate cognition deficits induced by DE and its precise mechanisms remain undetermined. In this study, DE was induced by streptozotocin (STZ, 150 mg/kg) in ICR mice. We observed the effect of astaxanthin on cognition and investigated its potential mechanisms in DE mice. Results showed that astaxanthin treatment significantly decreased the latency and enhanced the distance and time spent in the target quadrant in the Morris water maze test. Furthermore, neuronal survival was significantly increased in the hippocampal CA3 region and the frontal cortex following treatment with astaxanthin. Meanwhile, immunoblotting was used to observe the nuclear translocation of nuclear factor-kappaB (NF-kappaB) p65 and the expression of tumor necrosis factor-alpha (TNF-alpha) in the hippocampus and frontal cortex. The results indicated that astaxanthin could inhibit NF-kappaB nuclear translocation and downregulate TNF-alpha expression in the hippocampus and frontal cortex. Overall, the present study implied that astaxanthin could improve cognition by protecting neurons against inflammation injury potentially through inhibiting the nuclear translocation of NF-kappaB and down-regulating TNF alpha. PMID- 26272355 TI - Disclosing Health and Health Behavior Information between Living Donors and Their Recipients. AB - BACKGROUND AND OBJECTIVES: Living donor guidelines-both national and international-either do not address or are vague about what information can be shared between prospective living donors and transplant candidates, as well as when to make such disclosures and who should make them. This study explored the attitudes of donors and recipients regarding how much information they believe should be shared. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Two Email invitations were sent by the National Kidney Foundation (national headquarters) to its Email listservs, inviting members to participate in an online survey to assess the attitudes of kidney transplant stakeholders regarding the disclosure of health and health risk behavior information. RESULTS: From approximately 4200 unique Email addresses, 392 (9.3%) respondents completed part or all of the survey. The analyses were limited to the 236 respondents who self-identified as either donors (potential and actual, n=160) or recipients (candidates and actual, n=76). Overall, 79% (186 of 234) of respondents supported disclosure of general recipient health information that would affect post-transplant outcome to donors, and 88% (207 of 235) supported disclosure of general donor health information to recipients. Recipients and donors were also supportive of sharing donor and recipient information, particularly information relevant to graft and patient survival. There is some reticence, however, about sharing social information. The closer the relationship, the more information they are willing to share. Both donors and recipients wanted the transplant team involved in the information disclosure. Over three quarters of donors (79%) and recipients (78%) did not think the recipient had a right to know why a donor was excluded from donating. CONCLUSIONS: Both donors and recipients want a significant amount of health information to be disclosed. The opinions of other stakeholders need to be surveyed to determine whether a revision of current policies and practices is warranted. PMID- 26272356 TI - Inhibition of 2-methoxyestradiol glucuronidation by probenecid. AB - OBJECTIVES: 2-Methoxyestradiol (2ME2), a metabolite of estradiol, has antitumour activity in vitro. However, potential clinical applicability has been limited by low oral bioavailability. Probenecid was evaluated in vitro as an inhibitor of 2ME2 glucuronidation for purposes of enhancing 2ME2 oral bioavailability. METHODS: Human liver microsomes were used to determine kinetic parameters for transformation of 2ME2 to its glucuronide metabolites (M1, M2) and inhibition of the reactions by probenecid. KEY FINDINGS: M1 and M2 formation from 2ME2 proceeded with features of substrate inhibition. Probenecid inhibited metabolite formation, with mean inhibition constant (Ki ) values of 0.9 and 2.6 mM, respectively. Inhibition was reversible, with mixed competitive-non-competitive characteristics. CONCLUSION: The Ki values for probenecid inhibition of 2ME2 glucuronide formation, when compared to maximum probenecid plasma concentrations anticipated clinically, indicate that probenecid co-administration has the potential to augment systemic plasma levels of 2ME2 after oral dosage in humans. PMID- 26272357 TI - Health-related quality of life in perinatally HIV-infected children in the Netherlands. AB - Combination antiretroviral therapy (cART) can alter HIV infection in children into a chronic condition. Studies investigating health-related quality of life (HRQoL) in HIV-infected children are scarce, and lacking from Western Europe. This study aimed to compare the HRQoL of clinically stable perinatally HIV infected children to healthy, socioeconomically (SES)-matched controls as well as the Dutch norm population, and to explore associations between HIV and cART related factors with HRQoL. HIV-infected and healthy children aged 8-18 years completed the Pediatric Quality of Life InventoryTM 4.0 (PedsQLTM). We determined differences between groups on PedsQLTM mean scores, and the proportion of children with an impaired HRQoL per group (>=1 SD lower than the Dutch norm population). Logistic regression models were used to explore associations between disease-related factors and HRQoL impairment. In total, 33 HIV-infected and 37 healthy children were included. There were no differences in the mean PedsQLTM subscales between HIV-infected children and both control groups. The proportion of children with an impaired HRQoL was higher in the HIV-infected group (27%) as compared to the healthy control group (22%) and the Dutch norm (14%) on the school functioning subscale (HIV vs. Dutch norm: P = .045). Mean scores of HRQoL of perinatally HIV-infected children in the Netherlands were not different from a SES-matched control group, or from the Dutch norm population. However, the HIV infected group did contain more children with HRQoL impairment, suggesting that HIV-infected children in the Netherlands are still more vulnerable to a compromised HRQoL. PMID- 26272358 TI - The Usability of CAT System for Assessing the Depressive Level of Japanese-A Study on Psychometric Properties and Response Behavior. AB - BACKGROUND: An innovative measurement system using a computerized adaptive testing technique based on the item response theory (CAT) has been expanding to measure mental health status. However, little is known about details in its measurement properties based on the empirical data. Moreover, the response time (RT) data, which are not available by a paper-and-pencil measurement but available by a computerized measurement, would be worth investigating for exploring the response behavior. PURPOSE: We aimed at constructing the CAT to measure depressive symptomatology in a community population and exploring its measurement properties. Also, we examined the relationships between RTs, individual item responses, and depressive levels. METHOD: For constructing the CAT system, responses of 2061 workers and university students to 24 depression scale plus four negatively revised positive affect items were subjected to a polytomous IRT analysis. The stopping rule was set for standard error of estimation < 0.30 or the maximum 15 items displayed. The CAT and non-adaptive computer-based test (CBT) were administered to 209 undergraduates, and 168 of them administered again after 1 week. RESULTS: On average, the CAT was converged by 10.4 items. The theta values estimated by CAT and CBT were highly correlated (r = 0.94 and 0.95 for the 1st and 2nd measurements) and with the traditional scoring procedures (r's > 0.90). The test-retest reliability was at a satisfactory level (r = 0.86). RTs to some items significantly correlated with the theta estimates. The mean RT varied by the item contents and wording, i.e., the RT to positive affect items required additional 2 s or longer than the other subscale items. CONCLUSION: The CAT would be a reliable and practical measurement tool for various purposes including stress check at workplace. PMID- 26272359 TI - Decreased stathmin-1 expression inhibits trophoblast proliferation and invasion and is associated with recurrent miscarriage. AB - Fetal trophoblasts invade endometrium and establish a complex interaction with the maternal microenvironment during early pregnancy. However, the molecular mechanisms regulating trophoblast migration and invasion at the maternal-fetal interface remain poorly understood. Immunohistochemistry and immunoblotting have shown that stathmin-1 (STMN1) was down-regulated significantly in placental villi tissue and trophoblasts from patients with recurrent miscarriage. In vitro, overexpression of STMN1 promoted human trophoblast proliferation, migration, and invasion, whereas knockdown of STMN1 inhibited these processes. In addition, knockdown of STMN1 down-regulated N-cadherin and up-regulated E-cadherin in trophoblasts, whereas E-cadherin was up-regulated and N-cadherin was down regulated in recurrent miscarriage villi tissue. Knockdown of STMN1 attenuated cytoplasmic-nuclear translocation of beta-catenin and in turn down-regulated trophoblast matrix metalloproteases. Furthermore, tumor necrosis factor-alpha (TNF-alpha) down-regulated STMN1 expression, and serum TNF-alpha expression correlated inversely with trophoblast STMN1 levels. Interestingly, M1 macrophage derived TNF-alpha reduced trophoblast migration and invasion, and an anti-TNF alpha antibody reversed this effect. Collectively, this study indicated that STMN1 may play a key role in regulating trophoblast invasion, and that impaired STMN1 expression may lead to abnormal trophoblast invasion and result in recurrent miscarriage. PMID- 26272360 TI - Motor deficit in a tauopathy model is induced by disturbances of axonal transport leading to dying-back degeneration and denervation of neuromuscular junctions. AB - Several neurodegenerative diseases are characterized by both cognitive and motor deficits associated with accumulation of tau aggregates in brain, brainstem, and spinal cord. The Tg30 murine tauopathy model expresses a human tau protein bearing two frontotemporal dementia with Parkinsonism linked to chromosome 17 pathogenic mutations and develops a severe motor deficit and tau aggregates in brain and spinal cord. To investigate the origin of this motor deficit, we analyzed the age-dependent innervation status of the neuromuscular junctions and mutant tau expression in Tg30 mice. The human transgenic tau was detected from postnatal day 7 onward in motoneurons, axons in the sciatic nerve, and axon terminals of the neuromuscular junctions. The development and maturation of neuromuscular junctions were not disrupted in Tg30 mice, but their maintenance was disturbed in adult Tg30 mice, resulting in a progressive and severe muscle denervation. This muscle denervation was associated with early electrophysiological signs of muscle spontaneous activities and histological signs of muscle degeneration. Early loss of synaptic vesicles in axon terminals preceding motor deficits, accumulation of Gallyas-positive aggregates, and cathepsin-positive vesicular clusters in axons in the sciatic nerve suggest that this denervation results from disturbances of axonal transport. This physiopathological mechanism might be responsible for motor signs observed in some human tauopathies, and for synaptic dysfunction resulting from alterations at the presynaptic level in these diseases. PMID- 26272361 TI - Smad3 deficiency leads to mandibular condyle degradation via the sphingosine 1 phosphate (S1P)/S1P3 signaling axis. AB - Temporomandibular joint osteoarthritis is a degenerative disease that is characterized by permanent cartilage destruction. Transforming growth factor (TGF)-beta is one of the most abundant cytokines in the bone matrix and is shown to regulate the migration of osteoprogenitor cells. It is hypothesized that TGF beta/Smad3 signaling affects cartilage homeostasis by influencing sphingosine 1 phosphate (S1P)/S1P receptor signaling and chondrocyte migration. We therefore investigated the molecular mechanisms by which crosstalk may occur between TGF beta/Smad3 and S1P/S1P receptor signaling to maintain condylar cartilage and to prevent temporomandibular joint osteoarthritis. Abnormalities in the condylar subchondral bone, including dynamic changes in bone mineral density and microstructure, were observed in Smad3(-/-) mice by microcomputed tomography. Cell-free regions and proteoglycan loss characterized the cartilage degradation present, and increased numbers of apoptotic chondrocytes and matrix metalloproteinase 13(+) chondrocytes were also detected. Furthermore, expression of S1P receptor 3 (S1P3), but not S1P1 or S1P2, was significantly down-regulated in the condylar cartilage of Smad3(-/-) mice. By using RNA interference technology and pharmacologic tools, S1P was found to transactivate Smad3 in an S1P3/TGF-beta type II receptor-dependent manner, and S1P3 was found to be required for TGF-beta-induced migration of chondrocyte cells and downstream signal transduction via Rac1, RhoA, and Cdc42. Taken together, these results indicate that the Smad3/S1P3 signaling pathway plays an important role in the pathogenesis of temporomandibular joint osteoarthritis. PMID- 26272362 TI - The prognostic significance of CXCL16 and its receptor C-X-C chemokine receptor 6 in prostate cancer. AB - The chemokine CXCL16 and its receptor, C-X-C chemokine receptor (CXCR6), affect tumor progression through different pathways, including leukocyte recruitment and function, cellular senescence, tumor cell proliferation, survival, invasion, and metastasis. We examined how the expression of CXCL16/CXCR6 in prostate cancer (PC) was related to clinicopathological features and activation of inflammatory cells. Tissue microarrays from 535 patients were constructed from tumor epithelial and tumor stromal areas of primary PC. Immunohistochemistry was used to evaluate the expression of CXCL16/CXCR6, CD3(+) T cells (CD4(+), CD8(+)), and CD20(+) B cells. Survival analyses were used to evaluate their prognostic impact. Expression of CXCL16 in PC cell lines (DU145 and PC3) and the effect on proliferation and migration were examined. High expression levels of CXCL16 [hazard ratio (HR), 2.52; 95% CI, 1.12-5.68; P = 0.026] and CXCR6 (HR, 2.29; 95% CI, 1.10-4.82; P = 0.028) were each independent predictors for clinical failure. High co-expression of CXCL16 and CXCR6 (HR, 5.1; 95% CI, 1-15.9; P = 0.05) was associated with negative prognostic factors, such as Gleason grade 4 + 3, Gleason score >=7, vascular infiltration, and positive surgical margins. As a conclusion, high protein expression of CXCL16 and high protein co-expression of CXCL16/CXCR6 in PC were independent predictors for a worse clinical outcome. PMID- 26272363 TI - MAGED1 is a negative regulator of bone remodeling in mice. AB - Melanoma antigen family D1 (MAGED1), an important adaptor protein, has been shown to ubiquitously express and play critical roles in many aspects of cellular events and physiological functions. However, its role in bone remodeling remains unknown. We, therefore, analyzed the bone phenotype of Maged1-deficient mice. Maged1-deficient mice displayed a significant osteoporotic phenotype with a marked decrease in bone density and deterioration of trabecular architecture. Histomorphometric analysis demonstrated an increased mineral apposition rate as well as increased osteoclast number and surface in Maged1 knockout mice. At the cellular level, Maged1-deficient osteoblasts exhibited an increased proliferation rate and accelerated differentiation. MAGED1 deficiency also caused a promotion in osteoclastogenesis, and that was attributed to the cell autonomous acceleration of differentiation in osteoclasts and an increased receptor activator of NF-kappaB ligand/osteoprotegerin ratio, a major index of osteoclastogenesis, in osteoblasts. Thus, we identified MAGED1 as a novel regulator of osteoblastogenesis, osteoclastogenesis, and bone remodeling in a mouse model. PMID- 26272365 TI - New variant lymphomatoid papulosis type E preceding and coexisting with mycosis fungoides - a case report and review of the literature. AB - Angioinvasive (type E) lymphomatoid papulosis (LyP) is a recently described subtype of LyP presenting with eschar-like lesions that can be mistaken for aggressive forms of angiocentric cutaneous T-cell lymphoma. None of the cases of angioinvasive LyP described thus far have been associated with mycosis fungoides (MF). Herein, we describe a case of angioinvasive LyP type E coexisting with MF. The patient presented with an eschar on his chest and over time developed new nodules and large plaques with eschar formation, all of which resolved spontaneously over a period of a few weeks without intentional therapy. Biopsy revealed a CD30+ atypical inflammatory cell infiltrate with marked angiocentricity. Later, he developed erythematous annular scaly patches histologically consistent with MF. Our patient's clinical course confirms the indolent behavior characteristic of LyP despite the aggressive clinical and histologic appearance of lesions. The co-occurrence of angioinvasive LyP and MF in our patient highlights the propensity for LyP type E to coexist with MF, as is characteristic of other LyP subtypes, and supports the theory that LyP and MF are related T-cell lymphoproliferative disorders. Patients with LyP can present with large lesions exhibiting eschar formation and an atypical angiocentric/angiodestructive lymphoid infiltrate and should be spared overtreatment. PMID- 26272364 TI - Memory programming in CD8(+) T-cell differentiation is intrinsic and is not determined by CD4 help. AB - CD8(+) T cells activated without CD4(+) T-cell help are impaired in memory expansion. To understand the underlying cellular mechanism, here we track the dynamics of helper-deficient CD8(+) T-cell response to a minor histocompatibility antigen by phenotypic and in vivo imaging analyses. Helper-deficient CD8(+) T cells show reduced burst expansion, rapid peripheral egress, delayed antigen clearance and continuous activation, and are eventually exhausted. Contrary to the general consensus that CD4 help encodes memory programmes in CD8(+) T cells and helper-deficient CD8(+) T cells are abortive, these cells can differentiate into effectors and memory precursors. Importantly, accelerating antigen clearance or simply increasing the burst effector size enables generation of memory cells by CD8(+) T cells, regardless of CD4 help. These results suggest that the memory programme is CD8(+) T-cell-intrinsic, and provide insight into the role of CD4 help in CD8(+) T-cell responses. PMID- 26272366 TI - Ecological influences on individual differences in color preference. AB - How can the large, systematic differences that exist between individuals' color preferences be explained? The ecological valence theory (Palmer & Schloss, Proceedings of the National Academy of Sciences 107:8877-8882, 2010) posits that an individual's preference for each particular color is determined largely by his or her preferences for all correspondingly colored objects. Therefore, individuals should differ in their color preferences to the extent that they have different preferences for the same color-associated objects or that they experience different objects. Supporting this prediction, we found that individuals' color preferences were predicted better by their own preferences for correspondingly colored objects than by other peoples' preferences for the same objects. Moreover, the fit between color preferences and affect toward the colored objects was reliably improved when people's own idiosyncratic color object associations were included in addition to a standard set of color-object associations. These and related results provide evidence that individual differences in color preferences are reliably influenced by people's personal experiences with colored objects in their environment. PMID- 26272367 TI - Assessing stimulus-stimulus (semantic) conflict in the Stroop task using saccadic two-to-one color response mapping and preresponse pupillary measures. AB - Conflict in the Stroop task is thought to come from various stages of processing, including semantics. Two-to-one response mappings, in which two response-set colors share a common response location, have been used to isolate stimulus stimulus (semantic) from stimulus-response conflict in the Stroop task. However, the use of congruent trials as a baseline means that the measured effects could be exaggerated by facilitation, and recent research using neutral, non-color-word trials as a baseline has supported this notion. In the present study, we sought to provide evidence for stimulus-stimulus conflict using an oculomotor Stroop task and an early, preresponse pupillometric measure of effort. The results provided strong (Bayesian) evidence for no statistical difference between two-to one response-mapping trials and neutral trials in both saccadic response latencies and preresponse pupillometric measures, supporting the notion that the difference between same-response and congruent trials indexes facilitation in congruent trials, and not stimulus-stimulus conflict, thus providing evidence against the presence of semantic conflict in the Stroop task. We also demonstrated the utility of preresponse pupillometry in measuring Stroop interference, supporting the idea that pupillary effects are not simply a residue of making a response. PMID- 26272368 TI - Audio-visual object search is changed by bilingual experience. AB - The current study examined the impact of language experience on the ability to efficiently search for objects in the face of distractions. Monolingual and bilingual participants completed an ecologically-valid, object-finding task that contained conflicting, consistent, or neutral auditory cues. Bilinguals were faster than monolinguals at locating the target item, and eye movements revealed that this speed advantage was driven by bilinguals' ability to overcome interference from visual distractors and focus their attention on the relevant object. Bilinguals fixated the target object more often than did their monolingual peers, who, in contrast, attended more to a distracting image. Moreover, bilinguals', but not monolinguals', object-finding ability was positively associated with their executive control ability. We conclude that bilinguals' executive control advantages extend to real-world visual processing and object finding within a multi-modal environment. PMID- 26272369 TI - Expression, purification, refolding, and enzymatic characterization of two secretory phospholipases A2 from Neurospora crassa. AB - Secretory phospholipase A2 (sPLA2) catalyzes the hydrolysis of sn-2 linkage in the glycerophospholipid, thereby releasing fatty acid and 1-acyl lysophospholipid. Among sPLA2s from various organisms and tissues, group XIV fungal/bacterial sPLA2s are relatively less characterized compared to their mammalian counterparts. Here we report cloning, recombinant expression, refolding, and enzymatic characterization of two sPLA2s, NCU06650 and NCU09423, from the filamentous fungus Neurospora crassa. The hexahistidine-tagged putative mature region of both proteins was expressed in Escherichia coli. Inclusion bodies were solubilized using a high hydrostatic pressure refolding technique. NCU06650 was solubilized without any additives at alkaline pH, and the addition of arginine or non-detergent sulfobetain (NDSB) significantly improved the process at acidic pH. In contrast, NCU09423 was solubilized only when NDSB was added at alkaline pH. Both enzymes displayed a Ca(2+)-dependent lipolytic activity toward E. coli membrane. Mass spectrometry analysis using the synthetic phospholipids as substrates demonstrated that both enzymes preferentially cleaved the sn-2 ester linkage of substrates and generated 1-acyl lysophospholipids, demonstrating that they are bona fide PLA2. PMID- 26272370 TI - The human rhabdomyosarcoma cell line TE671--Towards an innovative production platform for glycosylated biopharmaceuticals. AB - The market of therapeutic glycoproteins (including coagulation factors, antibodies, cytokines and hormones) is one of the profitable, fast-growing and challenging sectors of the biopharmaceutical industry. Although mammalian cell culture is still expensive and technically complex, the ability to produce desired post-translational modifications, in particular glycosylation, is a major issue. Glycans can influence ligand binding, serum half-life as well as biological activity or product immunogenicity. Aiming to establish a novel production platform for recombinant glycoproteins, the human TE671 cell line was investigated. Since the initial analysis of cell membrane proteins showed a promising glycosylation of TE671 cells for biotechnological purposes, we focused on the recombinant expression of two model glycoproteins of therapeutical relevance. The optimization of the cell transfection procedure and serum-free expression succeeded for the human serine protease inhibitor alpha-1-antitrypsin (A1AT) and the hematopoietic cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). N-glycan analyses of both purified proteins by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry provided first fundamental insights into the TE671 glycosylation potential. Besides protein specific pattern, strong distinctions - in particular for N-glycan fucosylation and sialylation - were observed depending on the medium conditions of the respective TE671 cell cultivations. The cell line's ability to synthesize complex and highly sialylated N-glycan structures has been shown. Our results demonstrate the TE671 cell line as a serious alternative to other existing human expression systems. PMID- 26272371 TI - One-stage posterior spinal shortening by L5 partial spondylectomy for spondyloptosis or L5-S1 high-grade spondylolisthesis management. AB - STUDY DESIGN: A case series of seven consecutive patients with L5-S1 spondyloptosis (SPP) and Meyerding IV spondylolisthesis (HGSPL) treated consecutively by a new surgical technique with partial reduction and fixation after spinal shortening. OBJECTIVE: To report clinical and radiological outcomes of a spinal shortening procedure by a single posterior approach in seven patients with HGSPL and SPP. BACKGROUND DATA: The surgical treatment of L5-S1 SPP and HGSPL remains challenging, and numbers of surgical treatment options have been described with several principles. We reported a new surgical technique achieving partial reduction and fixation of L5-S1 SPP and HGSPL and highlighted its clinical and radiological outcomes. METHODS: Seven patients with Meyerding Grade IV (2), and Grade V (5) were operated consecutively between 2004 and 2011 for HGSPL and SPP. Surgery time, blood loss and complications were collected for all patients. The slip angle or Dubousset lumbo-sacral Angle (Dub-LSA), L5 slip percentage (%slip), pelvic tilt (PT), lumbar lordosis (LL), thoracic kyphosis (TK) and C7-tilt were measured pre and postoperatively. All patients underwent posterior one-stage decompression with sacral dome osteotomy, L5 vertebrectomy with L5-S1 discectomy, and partial reduction and instrumented fusion in a single posterior approach. RESULTS: The mean age and follow-up were, respectively, 20 years and 65 months. The mean preoperative %slip was 115 %, which improved to 63 % postoperatively. The mean preoperative Dub-LSA, PT, LL, TK, and C7-tilt were 37 degrees , 31 degrees , -74 degrees , 30 degrees , and 6 degrees , respectively, which improved to 94 degrees , 25 degrees , -44 degrees , 42 degrees and -0.14 degrees postoperatively. No implant failure or pseudarthrosis were reported at last follow-up. CONCLUSION: This novel and efficient one-stage shortening technique offers the possibility to manage lumbosacral kyphosis and spinal local malalignment in L5-S1 SPP. PMID- 26272372 TI - Safety and compatibility of magnetic-controlled growing rods and magnetic resonance imaging. AB - PURPOSE: Magnetically controlled growth rods (MCGRs) are a new technology for the management of early-onset pediatric deformity enabling guided spinal growth by controlling the curvature. These rods contain a rare earth magnet and are contraindicated for MRI. We have investigated the behavior MCGRs to determine whether MRI adversely affects rod properties and to determine the extent of image distortion. METHODS: This is an in vitro experiment using two magnetic growth rods secured in a 1.5 T MRI. A gradient echo sequence MRI was performed to evaluate whether the rods elongated, contracted or rotated during scanning and a phantom model was used to evaluate the amount of artifact induced. RESULTS: The rod was not activated or subsequently impaired by the process of MRI. Image distortion of 28.9 cm along the long axis of the magnet and 20.1 cm perpendicular to this was seen with extension 10.6 cm cranial to the magnet housing. No negative effect was demonstrated on the magnetic rod elongation mechanism. CONCLUSIONS: This study has demonstrated that there are no detrimental effects of MRI on the MCGR and imaging of the head and neck phantom can still be interpreted. Further in vivo study is warranted. PMID- 26272375 TI - Minimally invasive instrumentation of uncomplicated cervical fractures. AB - PURPOSE: Many authors favor conservative treatment options in oligo-symptomatic non-dislocated cervical fractures. This is mainly because of adverse events, anesthesia times and blood loss associated with surgical treatment of these injuries. We, therefore, sought to minimize the invasiveness of the surgical treatment of simple cervical fractures using image-guidance and a percutaneous approach. METHODS: Iso-C3D-based image guidance was used to place unilateral lag screws and conventional screws in pedicles, isthmi and lateral masses C1-C6. The navigation reference marker array was attached to the Mayfield clamp avoiding any additional skin incisions. Drilling of the screws trajectories was performed using a high speed drill with diamond tip, minimizing the risk of dislocations of cervical vertebrae and/or bone fragments relative to the iso-C3D scan to which the navigation system was registered. RESULTS: Image-guided percutaneous placement of cervical pedicle, isthmic and lateral mass screws resulted in correct screw placement in all six cases (three hangman fractures, three odontoid fracture Anderson 2 in elderly patients and one C6 posttraumatic pedicular pseudoarthrosis). Average blood loss was 194 ml, total average operating time 106 min and average X-ray time 3.8 min (395 cGy/cm(2)) including iso-C3D imaging. CONCLUSION: The technique presented here was found to be a feasible minimally invasive treatment option for uncomplicated cervical fractures. Besides to our best knowledge, we here present the first percutaneous implantation of lateral mass screws. PMID- 26272373 TI - Risk factors for adjacent segment pathology requiring additional surgery after single-level spinal fusion: impact of pre-existing spinal stenosis demonstrated by preoperative myelography. AB - PURPOSE: We determined the incidence of and risk factors for clinical adjacent segment pathology (C-ASP) requiring additional surgeries among patients previously treated with one-segment lumbar decompression and fusion surgery. METHODS: We retrospectively analysed 161 consecutive patients who underwent one segment lumbar decompression and fusion surgery for L4 degenerative spondylolisthesis. Patient age, sex, body mass index (BMI), facet orientation and tropism, laminar inclination angle, spinal canal stenosis ratio [on myelography and magnetic resonance imaging (MRI)], preoperative adjacent segment instability, arthrodesis type, pseudarthrosis, segmental lordosis at L4-5, and the present L4 slip were evaluated by a log-rank test using the Kaplan-Meier method. A multivariate Cox proportional-hazards model was used to analyse all factors found significant by the log-rank test. RESULTS: Of 161 patients, 22 patients (13.7 %) had additional surgeries at cranial segments located adjacent to the index surgery's location. Pre-existing canal stenosis >=47 % at the adjacent segment on myelography, greater facet tropism, and high BMI were significant risk factors for C-ASP. The estimated incidences at 10 years postoperatively for each of these factors were 51.3, 39.6, and 32.5 %, and the risks for C-ASP were 4.9, 3.7, and, 3.1 times higher than their counterparts, respectively. Notably, spinal canal stenosis on myelography, but not on MRI, was found to be a significant risk factor for C-ASP (log-rank test P < 0.0001 and 0.299, respectively). CONCLUSIONS: Pre-existing spinal stenosis, greater facet tropism, and higher BMI significantly increased C-ASP risk. Myelography is a more accurate method for detecting latent spinal canal stenosis as a risk factor for C-ASP. PMID- 26272374 TI - What is the preclinical evidence on platelet rich plasma and intervertebral disc degeneration? AB - PURPOSE: Intervertebral disc degeneration is a common disease that usually starts from the third decade of life and it represents a significant cause of socio economic problems. The accepted surgical treatment for disc degeneration is disc removal and vertebral fusion or, in selected cases, intervertebral disc arthroplasty. Several studies have demonstrated the ability of platelet rich plasma (PRP) to stimulate cell proliferation and extracellular matrix regeneration. However, literature results are still limited and more studies are required to clarify the role of PRP in the prevention or in the treatment of degenerative disc disease. The aim of this review is to summarize and critically analyze the current preclinical evidence about the use of PRP in intervertebral disc degeneration. METHODS: Literature search was performed through various combinations of the following keywords: Intervertebral Disc Degeneration, Platelet Rich Plasma, PRP, Intervertebral disc regeneration. Papers included in our review cover the period between 2006 and 2014. The PRISMA 2009 checklist was followed. RESULTS: At the end of the review process, 12 articles were included in our final manuscript, including 6 "in vitro" and 6 "in vivo" studies. All the included studies lead to positive preclinical results. No standardization of methodological analysis was observed. CONCLUSION: It is not possible to draw definitive evidence about the use of PRP in IVD regeneration. We advise a proper standardization of the methodological analysis in order to compare the available data and achieve definitive results. This should be the cornerstone for future clinical applications. PMID- 26272378 TI - The transmembrane heparan sulphate proteoglycan syndecan-4 is involved in establishment of the lamellar structure of the annulus fibrosus of the intervertebral disc. AB - The annulus fibrosus of the intervertebral disc unites adjacent vertebral bodies along the length of the spine and provides tensile resistance towards compressive, twisting and bending movements arising through gait. It consists of a nested series of oriented collagenous lamellae, arranged in cross-ply circumferentially around the nucleus pulposus. The organisation of oriented collagen in the annulus is established during foetal development by an identical arrangement of oriented fibroblasts that are precisely organised into cell sheets, or laminae. These provide a template for ordered deposition of extracellular matrix material on cell surfaces, by means of a poorly understood mechanism involving the actin cytoskeleton. In this study, we investigate the role of two cell surface heparan sulphate proteoglycans (HSPGs), glypican-6 and syndecan-4, in the matrix assembly process in the developmental rat intervertebral disc. We compare their expression patterns with those of heparan sulphate and the interactive, cell-surface adhesive glycoprotein, fibronectin, and relate these to the stage-specific collagenous architectures present within the annulus at both light and electron microscopic levels. We show that both proteoglycans are strongly associated with the development, growth and aging of the intervertebral disc. Furthermore, the immunohistochemical labelling patterns suggest that syndecan-4, in particular, plays a potentially-significant role in annulus formation. We propose that this HSPG mediates interaction between the actin cytoskeleton and nascent extracellular matrix in the lamellar organisation of annulus tissue. These data add considerably towards an understanding of how cells organise and maintain complex, oriented extracellular matrices and has particular clinical relevance to the fields of tissue engineering and repair. PMID- 26272376 TI - Application of protein misfolding cyclic amplification to detection of prions in anaerobic digestate. AB - The exceptional physio-chemical resistance of prions to established decontamination procedures poses a challenge to assessing the suitability of applied inactivation methods. Prion detection is limited by the sensitivity level of Western blotting or by the cost and time factors of bioassays. In addition, prion detection assays can be limited by either the unique or complex nature of matrices associated with environmental samples. To investigate anaerobic digestion (AD) as a practical and economical approach for potential conversion of specified risk materials (SRM) into value added products (i.e., renewable energy), challenges associated with detection of prions in a complex matrix need to be overcome to determine potential inactivation. Protein misfolding cyclic amplification (PMCA) assay, with subsequent Western blot visualization, was used to detect prions within the AD matrix. Anaerobic digestate initially inhibited the PMCA reaction and/or Western blot detection. However, at concentrations of <=1% of anaerobic digestate, 263K scrapie prions could be amplified and semi quantitatively detected. Infectious 263K prions were also proven to be bioavailable in the presence of high concentrations of digestate (10-90%). Development of the PMCA application to digestate provides extremely valuable insight into the potential degradation and/or fate of prions in complex biological matrices without requiring expensive and time-consuming bioassays. PMID- 26272379 TI - Health and pink-collar work. AB - BACKGROUND: In recent years, there has been a decline in the manufacturing sector of the UK economy with a corresponding growth of service-orientated pink-collar jobs in some regions. While the health outcomes of white- and blue-collar workers are well-established, less is known about this emerging pink-collar group. AIMS: To outline the health of pink-collar workers in comparison to their white-collar counterparts across a range of indicators. METHODS: Area-level percentages for white-, pink- and blue-collar workers were derived from residents' routinely collected employment data in a northern English town. Area-level health data pertaining to male and female life expectancy, respiratory deaths and deaths from cardiovascular and circulatory causes (all age and under 75 years) were obtained from the local authority and public health observatory. Multivariate regression analyses were performed to assess relationships between job collar and health. RESULTS: When adjusted for deprivation, areas with higher percentages of pink collar workers experienced lower rates of death from circulatory disease under the age of 75 in comparison to white-collar workers. Other relationships between collar status and health outcomes were not statistically significant. CONCLUSIONS: The reasons underlying the apparent protective effect of pink-collar status for deaths from circulatory disease are uncertain and merit further study. Possibilities include differences in age, exposure to occupational hazards and lifestyle behaviours. Our work has a number of limitations and longitudinal studies with detailed exposure data should assess the long-term health outcomes of these workers using agreed definitions. PMID- 26272377 TI - Development of molecular tools to monitor conjugative transfer in rhizobia. AB - Evolution of bacterial populations has been extensively driven by horizontal transfer events. Conjugative plasmid transfer is considered the principal contributor to gene exchange among bacteria. Several conjugative and mobilizable plasmids have been identified in rhizobia, and two major molecular mechanisms that regulate their transfer have been described, under laboratory conditions. The knowledge of rhizobial plasmid transfer regulation in natural environments is very poor. In this work we developed molecular tools to easily monitor the conjugative plasmid transfer in rhizobia by flow cytometry (FC) or microscopy. 24 cassettes were constructed by combining a variety of promotors, fluorescent proteins and antibiotic resistance genes, and used to tag plasmids and chromosome of donor strains. We were able to detect plasmid transfer after conversion of non fluorescent recipients into fluorescent transconjugants. Flow cytometry (FC) was optimized to count donor, recipient and transconjugant strains to determine conjugative transfer frequencies. Results were similar, when determined either by FC or by viable counts. Our constructions also allowed the visualization of transconjugants in crosses performed on bean roots. The tools presented here may also be used for other purposes, such as analysis of transcriptional fusions or single-cell tagging. Application of the system will allow the survey of how different environmental conditions or other regulators modulate plasmid transfer in rhizobia. PMID- 26272380 TI - Repeatability of a cold stress test to assess cold sensitization. AB - BACKGROUND: Non-freezing cold injury (NFCI) is a syndrome in which damage to peripheral tissues occurs without the tissues freezing following exposure to low ambient temperatures. AIMS: To assess the test-retest reliability of a cold stress test (CST) used to assess cold sensitization. METHODS: Volunteers with no self-reported history of NFCI undertook the CST on three occasions. Thermal images were taken of the foot and hand before, immediately after and 5min after immersion of the limb in cold water for 2min. Cold sensitization was graded by the two clinicians and the lead author. Spot temperatures from the toe and finger pads were recorded. RESULTS: There were 30 white and 19 black male participants. The ratings indicated substantial agreement [a Cohen's kappa (kappa) value of 0.61-0.8] to within +/- one grading category for the hands and feet of the white volunteers and the hands of the black volunteers. Limits of agreement (LoA) analysis for toe and finger pad temperatures indicated high agreement (absolute 95% LoA < 5.5 degrees C). Test-retest reliability for the feet of the black volunteers was not supported by the gradings (kappa = 0.38) and toe pad temperatures (absolute 95% LoA = 9.5 degrees C and coefficient of variation = 11%). CONCLUSIONS: The test-retest reliability of the CST is considered adequate for the assessment of the cold sensitization of the hands and feet of white and the hands of black healthy non-patients. The study should be repeated with patients who have suffered a NFCI. PMID- 26272382 TI - Potential risk factors for haematological cancers in semiconductor workers. AB - BACKGROUND: There has recently been increased interest in cancer incidence in electronics workers. AIMS: To determine the cancer incidence ratio in electronics workers and the potential factors affecting the risk for development of cancer. METHODS: Epidemiological study performed in electronics workers who were employed between 1999 and 2008 in South Korea. Cancer incidence ratio was analysed with respect to departments, divisions, job titles, gender, age, hepatitis B and C virus infection and work duration. We compared the incidence of haematological cancer in this cohort with that expected in the general population. RESULTS: The study population was 56283. Overall, the standardized incidence ratio (SIR) for haematological cancer was 0.85. In particular, the SIR for leukaemia was 0.86 and for non-Hodgkin lymphoma (NHL) was 0.93, which were not statistically significant. The SIR for NHL was significantly increased [SIR 5.23, 95% confidence interval (CI) 1.31-20.95] in female office workers. We also found that the SIR for NHL was significantly increased in female workers who tested positive for hepatitis virus infection (SIR 7.69, 95% CI 1.08-54.60). CONCLUSIONS: The raised SIR for NHL among female workers was due to potential risk factors such as hepatitis virus infection although additional research and an ongoing, long-term, prospective epidemiological cohort study is needed. PMID- 26272381 TI - Occupational asphalt is not associated with head and neck cancer. AB - BACKGROUND: Epidemiologic studies that evaluate the relationship between occupational asphalt exposure and head and neck cancer have had a limited ability to control for known risk factors such as smoking, alcohol and human papillomavirus (HPV). AIMS: To better elucidate this relationship by including known risk factors in a large case-control study of head and neck squamous cell carcinoma (HNSCC) from the greater Boston area. METHODS: We analysed the relationship between occupational asphalt exposure and HNSCC among men in the Greater Boston area of Massachusetts. Analyses were conducted using unconditional multivariable logistic regression, performed with adjustments for age, race, education, smoking, alcohol consumption and HPV serology. RESULTS: There were 753 cases and 913 controls. No associations between HNSCC and occupational asphalt exposure (neither among ever-exposed nor by occupational duration) were observed for exposures in any occupation or those restricted to the construction industry. We also observed no associations in subgroup analyses of never-smokers and ever smokers. Adjusting for known risk factors further reduced the estimated effect of asphalt exposure on HNSCC risk. CONCLUSIONS: We found no evidence for an association between occupational asphalt exposure and HNSCC. The null findings from this well-controlled analysis could suggest that the risk estimates stemming from occupational cohort studies may be overestimated due to uncontrolled confounding and enhance the literature available for weighing cancer risk from occupational exposure to bitumen. PMID- 26272383 TI - Association Between Anemia and Cerebral Venous Thrombosis: Case-Control Study. AB - BACKGROUND AND PURPOSE: Anemia is often considered to be a risk factor for cerebral venous thrombosis (CVT), but this assumption is mostly based on case reports. We investigated the association between anemia and CVT in a controlled study. METHODS: Unmatched case-control study: cases were adult patients with CVT included in a single-center, prospective database between July 2006 and December 2014. Controls were subjects from the control population of the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis (MEGA) study. Anemia was defined according to World Health Organization criteria: nonpregnant women hemoglobin<7.5 mmol/L, pregnant women<6.9 mmol/L, and men<8.1 mmol/L. We used logistic regression analysis, adjusting for age, sex, malignancy, oral contraceptive use, and pregnancy/puerperium. RESULTS: We included 152 cases and 2916 controls. Patients with CVT were younger (mean age, 40 versus 48 years) and more often women (74% versus 53%) than controls. Anemia was more frequent in cases (27.0%) than in controls (6.5%; P<0.001). Anemia was associated with CVT, both in univariate analysis (odds ratio, 5.3; 95% confidence interval [CI], 3.6 7.9) and after adjustment for potential confounders (adjusted odds ratio, 4.4; 95% CI, 2.8-6.9). Hemoglobin as a continuous variable was inversely associated with CVT (adjusted odds ratio per 1 mmol/L change 0.53; 95% CI, 0.42-0.66). Stratification by sex showed a stronger association between anemia and CVT in men (adjusted odds ratio, 9.9; 95% CI, 4.1-23.8) than in women (3.6; 95% CI, 2.1 6.0). CONCLUSION: Our data suggest that anemia is a risk factor for CVT. PMID- 26272384 TI - Modeling Ischemia in the Immature Brain: How Translational Are Animal Models? PMID- 26272385 TI - Point-of-Care Testing of Coagulation in Patients Treated With Non-Vitamin K Antagonist Oral Anticoagulants. AB - BACKGROUND AND PURPOSE: Specific coagulation assays for non-vitamin K antagonist oral anticoagulants (NOAC) are relatively slow and often lack availability. Although specific point-of-care tests (POCT) are currently not available, NOAC are known to affect established coagulation POCT. This study aimed at determining the diagnostic accuracy of the CoaguChek POCT to rule out relevant concentrations of rivaroxaban, apixaban, and dabigatran in real-life patients. METHODS: We consecutively enrolled 60 ischemic stroke patients newly started on NOAC treatment and obtained blood samples at 6 prespecified time points. Samples were tested using the CoaguChek POCT, laboratory-based coagulation assays (prothrombin time and activated partial thromboplastin time, anti-Xa test and Hemoclot), and liquid chromatography-tandem mass spectrometry for direct determination of NOAC concentrations. RESULTS: Three hundred fifty-six blood samples were collected. The CoaguChek POCT strongly correlated (r=0.82 P<0.001) with rivaroxaban concentrations but did not accurately detect dabigatran or apixaban. If used to estimate the presence of low rivaroxaban concentrations, POCT was superior to predictions based on normal prothrombin time and activated partial thromboplastin time values even if sensitive reagents were used. POCT-results<=1.0 predicted rivaroxaban concentrations<32 and <100 ng/mL with a specificity of 90% and 96%, respectively. CONCLUSIONS: If anti-Xa test is not available, we propose the use of the CoaguChek POCT to guide thrombolysis decisions after individual risk assessment in rivaroxaban-treated patients having acute ischemic stroke. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02371044. PMID- 26272386 TI - Prognostic Factors for Cognitive Decline After Intracerebral Hemorrhage. AB - BACKGROUND AND PURPOSE: Stroke and dementia are closely related, but no prospective study ever focused on poststroke cognitive decline in patients with intracerebral hemorrhage (ICH). We aimed to determine prognostic factors for cognitive decline in patients with ICH. METHODS: We prospectively included 167 consecutive ICH survivors without preexisting dementia from the Prognosis of Intra-Cerebral Hemorrhage (PITCH) cohort. Median follow-up was 4 years (interquartile range, 2.3-5.4). We explored factors associated with cognitive decline using linear mixed models. Cognitive decline was determined based on repeated mini-mental state examination. We investigated each prognostic factor separately in univariate models. Next, we constructed clinical and radiological multivariable models. In a sensitivity analysis, we excluded patients with preexisting cognitive impairment. RESULTS: Median age was 64 (interquartile range, 53-75) years, 69 (41%) patients were women, and median mini-mental state examination at 6 months was 27 (interquartile range, 23-29). Overall, 37% of the patients declined during follow-up. Factors associated with cognitive decline in univariate analyses were previous stroke or transient ischemic attack, preexisting cognitive impairment, microbleed presence, severity of white matter hyperintensities, and severity of cortical atrophy. In multivariable analyses, previous stroke or transient ischemic attack (beta [SE], -0.55 [0.23]; P<0.05), preexisting cognitive impairment (beta [SE], -0.56 [0.25]; P<0.01), and severity of cortical atrophy (beta [SE], -0.50 [0.19]; P<0.01) remained independent prognostic factors. In patients without preexisting cognitive impairment (n=139), severity of cortical atrophy (beta [SE], -0.38 [0.17]; P<0.05) was the only prognostic factor for future cognitive decline. CONCLUSIONS: Prognostic factors for cognitive decline after ICH are already present when ICH occurs, suggesting a process of ongoing cognitive impairment instead of new-onset decline induced by the ICH itself. PMID- 26272387 TI - Hospital Readmission Rates Among Mechanically Ventilated Patients With Stroke. AB - BACKGROUND AND PURPOSE: Tracheostomy is frequently performed in patients with severe ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage. Little is known about readmission rates among stroke patients who undergo mechanical ventilation. METHODS: We used previously validated International Classification of Diseases, Ninth Edition-Clinical Modification codes and data on all discharges from nonfederal acute care hospitals in 3 states. We compared readmission rates among mechanically ventilated patients with stroke who were discharged with or without a tracheostomy. RESULTS: Among 39,881 patients who underwent mechanical ventilation during the index stroke hospitalization and survived to discharge, 10,690 (26.8%; 95% confidence interval, 26.4%-27.2%) underwent tracheostomy. During a mean follow-up period of 3.4 (+/-2.0) years, the overall incidence rate of readmissions was 4.25 (95% confidence interval, 4.22 4.28) per 100 patients per 30 days. The rate of any readmissions within 30 days was 26.9% among patients with tracheostomy compared with 22.5% among those without a tracheostomy (absolute risk difference, 4.4%; 95% confidence interval, 3.5%-5.4%; P<0.001). After adjustment for potentially confounding variables, tracheostomy was associated with a slightly increased readmission rate (incidence rate ratio, 1.07; 95% confidence interval, 1.03-1.11). CONCLUSIONS: Approximately one quarter of mechanically ventilated patients with stroke who survive to discharge are readmitted to the hospital within 30 days. Readmission rates are significantly higher in patients with stroke who undergo tracheostomy, but the difference is not clinically meaningful. Thirty-day readmission rates among mechanically ventilated patients with stroke are similar to Medicare beneficiaries hospitalized with major medical diseases such as pneumonia. PMID- 26272388 TI - Intracellular and membrane-damaging activities of methyl gallate isolated from Terminalia chebula against multidrug-resistant Shigella spp. AB - Shigella spp. (Shigella dysenteriae, Shigella flexneri, Shigella boydii and Shigella sonnei) cause bacillary dysentery (shigellosis), which is characterized by bloody mucous diarrhoea. Although a variety of antibiotics have been effective for treatment of shigellosis, options are becoming limited due to globally emerging drug resistance. In the present study, in vitro antibacterial activity of methyl gallate (MG) isolated from Terminalia chebula was determined by performing MIC, minimal bactericidal concentration (MBC) and time-kill kinetic studies. Bacterial membrane-damaging activity of MG was determined by membrane perturbation and transmission electron microscopy (TEM). Cellular drug accumulation, cell infection and assessment of intracellular activities of MG and reference antibiotics were performed using HeLa cell cultures. The bactericidal activity of MG against multidrug-resistant (MDR) Shigella spp. in comparison with other commonly used drugs including fluoroquinolone was demonstrated here. TEM findings in the present study revealed that MG caused the total disintegration of inner and outer membranes, and leakage of the cytoplasmic contents of S. dysenteriae. The level of accumulation of MG and tetracycline in HeLa cells incubated for 24 h was relatively higher than that of ciprofloxacin and nalidixic acid (ratio of intracellular concentration/extracellular concentration of antibiotic for MG and tetracycline>ciprofloxacin and nalidixic acid). The viable number of intracellular S. dysenteriae was decreased in a time-dependent manner in the presence of MG (4 * MBC) and reduced to zero within 20 h. The significant intracellular activities of MG suggested that it could potentially be used as an effective antibacterial agent for the treatment of severe infections caused by MDR Shigella spp. PMID- 26272390 TI - Removing chiral contamination of lactate solutions by selective metabolism of the D-enantiomer. AB - OBJECTIVE: A bio-based process is appealing for purification of L-lactic acid, the major enantiomer of polylactic acid syrup, generated by thermochemical processes at the end of life of PLA-based plastics, from its chiral impurity, D lactic acid, before reuse. RESULTS: Polylactic acid (PLA), a renewable alternative to petroleum-derived plastics, contains a mixture of L- and D-lactic acid (LA) isomers with the L-isomer dominating (up to 95 %). A novel bio-based process was developed to produce chirally pure L-LA from syrup produced during recycling of PLA-plastics. This process utilizes an engineered Escherichia coli (strain DC1001) containing novel gene deletions (lld, ykg) that eliminated the oxidative metabolism of L-lactate, leaving the membrane-bound D-lactate dehydrogenases to selectively metabolize the D-isomer. Strain DC1001 removed 8.7 g D-lactate l(-1) from a PLA-syrup containing 135 g total lactic acid l(-1) in 24 h. Average rates of removal of D-lactic acid were 0.25 g D-lactate h(-1) (g cell dry weight)(-1) and 0.36 g D-lactate l(-1) h(-1). CONCLUSION: Bio-based purification of PLA-syrup utilizing E. coli strain DC1001 is an attractive process step during recycling of PLA-plastics. This selective oxidation process can also be used to remove chiral contamination of L-lactate in medical applications. PMID- 26272389 TI - Generation of monoclonal antibodies against MGA and comparison of their application in breast cancer detection by immunohistochemistry. AB - Mammaglobin A (MGA) is an organ specific molecular biomarker for metastatic breast cancer diagnosis. However, there are still needs to develop optimal monoclonal antibodies (mAbs) to detect MGA expression in breast carcinoma by immunohistochemistry. In this study, we first generated mAbs against MGA. Then, we used epitope prediction and computer-assisted structural analysis to screen five dominant epitopes and identified mAbs against five epitopes. Further immunohistochemical analysis on 42 breast carcinoma specimens showed that MHG1152 and MGD785 had intensive staining mainly in membrane, while CHH11617, CHH995 and MJF656 had more intensive staining within the cytoplasm. MGA scoring results showed that MJF656 had the highest rate (92.8%) of positive staining among five mAbs, including higher staining intensity when compared with that of MHG1152 (p < 0.01) and CHH995 (p < 0.05) and the highest the mean percentage of cells stained among mAbs. Furthermore, we analyzed the relationship of positive staining rate by mAbs with patient clinical characteristics. The results suggest that MJF656 was able to detect MGA expression, especially in early clinical stage, low grade and lymph node metastasis-negative breast carcinoma. In conclusion, our study generated five mAbs against MGA and identified the best candidate for detection of MGA expression in breast cancer tissues. PMID- 26272391 TI - High doses of (-)-epigallocatechin-3-gallate from green tea induces cardiac fibrosis in mice. AB - OBJECTIVE: Tea is the most consumed beverage in the world. (-)-Epigallocatechin-3 gallate (EGCG), a major green tea polyphenol, is effective in the prevention of several chronic diseases, and is marketed as part of many dietary supplements. We have now examined the myocardiotoxic effect of high doses of EGCG in mice. RESULTS: EGCG (500 and 1000 mg/kg.d) induced cardiac collagen synthesis and fibrosis-related protein expression, such as connective tissue growth factor (CTGF) and fibronectin (FN) in mice. Moreover, EGCG decreased the protein expression of p-AMPK and increased the levels of p-p70S6 K and p-S6. CONCLUSION: This is the first evidence that high oral doses of EGCG could induce cardiac fibrosis, and shed new light on the understanding of EGCG-mediated myocardiotoxicity. PMID- 26272392 TI - Xanthomonas campestris expansin-like X domain is a structurally disordered beta sheet macromolecule capable of synergistically enhancing enzymatic efficiency of cellulose hydrolysis. AB - OBJECTIVES: To biochemically characterize an expansin-like X protein domain from Xanthomonas campestris (XcEXLX1) and to study its synergy with cellulases in cellulose depolymerization. RESULTS: The protein was purified using a combination of ion exchange and size exclusion chromatography rendering about 30 mg pure protein/l culture medium. Circular dichroism spectroscopy and small-angle X-ray scattering studies of XcEXLX1 reveal that it is a strongly disordered beta-sheet protein. Its low resolution envelope fits nicely the crystallographic structure of the homologous protein EXLX1 from Bacillus subtillis. Furthermore, we demonstrate that XcEXLX1 shows a synergistic, pH-dependent effect when combined with a commercial enzymatic preparation (Accellerase 1500), enhancing its hydrolytic activity on a cellulosic substrate. The strongest effect was observed in acid pHs with an increase in sugar release of up to 36 %. CONCLUSION: The synergistic effect arising from the action of the expansin-like protein was considerable in the presence of significantly larger amounts of the commercial enzymatic cocktail then previously observed (0.35 FPU of Accellerase 1500/g substrate). PMID- 26272393 TI - Microbial fuel cells for biosensor applications. AB - Microbial fuel cells (MFCs) face major hurdles for real-world applications as power generators with the exception of powering small sensor devices. Despite tremendous improvements made in the last two decades, MFCs are still too expensive to build and operate and their power output is still too small. In view of this, in recently years, intensive researches have been carried out to expand the applications into other areas such as acid and alkali production, bioremediation of aquatic sediments, desalination and biosensors. Unlike power applications, MFC sensors have the immediate prospect to be practical. This review covers the latest developments in various proposed biosensor applications using MFCs including monitoring microbial activity, testing biochemical oxygen demand, detection of toxicants and detection of microbial biofilms that cause biocorrosion. PMID- 26272394 TI - A novel terpenoid indole alkaloid derived from catharanthine via biotransformation by suspension-cultured cells of Catharanthus roseus. AB - OBJECTIVE: Although catharanthine (1) is well known as a biosynthetic precursor of the anticancer alkaloid, vinblastine, its alternative metabolic pathways are unclear. RESULTS: Biotransformation of 1 by suspension-cultured cells of Catharanthus roseus gave a new oxidative-cleavage product (2). The structure of 2 was determined as 3-hydroxy-4-imino-catharanthine by spectroscopic methods. Maximum conversion (9.75 %) of 2 was observed after 120 h adding 6 mg of 1/100 ml to 12-day-old suspension-cultured cells of C. roseus. Furthermore, qRT-PCR experiment was performed to reveal the effect of 1 on the expression of the genes in the biosynthetic pathway of TIA 1 up-regulated the transcript level of D4H whilst down-regulating the transcript levels of G10H, LAMT, GES, and IRS. CONCLUSION: A new metabolite of catharanthine, 3-hydroxy-4-imino-catharanthine, is reported. PMID- 26272395 TI - Long-term response on growth, antioxidant enzymes, and secondary metabolites in salicylic acid pre-treated Uncaria tomentosa microplants. AB - OBJECTIVE: To obtain micro propagated Uncaria tomentosa plantlets with enhanced secondary metabolites production, long-term responses to salicylic acid (SA) pre treatments at 1 and 100 uM were evaluated after propagation of the plantlets in a SA-free medium. RESULTS: SA pre-treatments of single node cuttings OF U. tomentosa produced long-term responses in microplants grown for 75 days in a SA free medium. Reduction in survival rate, root formation, and stem elongation were observed only with 100 uM SA pre-treatments with respect to the control (0 + DMSO).Both pre-treatments enhanced H2O2 and inhibited superoxide dismutase and catalase activities, while guaiacol peroxidase was increased only with 1 uM SA. Also, both pre-treatments increased total monoterpenoid oxindole alkaloids by ca. 55 % (16.5 mg g(-1) DW), including isopteropodine, speciophylline, mitraphylline, isomitraphylline, rhynchopylline, and isorhynchopylline; and flavonoids by ca. 21 % (914 MUg g(-1) DW), whereas phenolic compounds were increased 80 % (599 MUg g( 1) DW) at 1 uM and 8.2 % (359 MUg g(-1) DW) at 100 uM SA. CONCLUSION: Pre treatment with 1 uM SA of U.tomentosa microplants preserved the survival rate and increased oxindole alkaloids, flavonoids, and phenolic compounds in correlation with H2O2 and peroxidase activity enhancements, offering biotechnological advantages over non-treated microplants. PMID- 26272396 TI - Characterization of the phenolic fraction from Argentine wine and its effect on viability and polysaccharide production of Pediococcus pentosaceus. AB - OBJECTIVES: To qualitatively and quantitatively characterize a low molecular weight phenolic fraction (LMF) of Malbec wine from Cafayate, Argentina, and evaluate its effect on viability and exopolysaccharide production of Pediococcus pentosaceus 12p, a wine spoilage bacterium. RESULTS: The phenolic compounds detected were, in general, comparable to data previously reported but hydroxycinnamic acids were detected at higher concentrations than determined in other studies. Addition of LMF at identical concentrations present in wine or a four times concentrated LMF mixture to a synthetic wine-like medium produced a diminution in bacterial viability and exopolysaccharide production in the supernatant culture. Transmission electron microscopy revealed damage of bacterial cell integrity after 96 h of incubation only in the presence of four times concentrated LMF. CONCLUSION: This is the first time a low molecular weight phenolic fraction has been characterized in Cafayate wine and it has demonstrated a marked antimicrobial effect on an exopolysaccharide-producing wine spoilage bacterium. PMID- 26272397 TI - Development of an ELISA based on a multi-fragment antigen of infectious bronchitis virus for antibodies detection. AB - OBJECTIVES: To develop a cost-effective ELISA for detection of antibodies against infectious bronchitis virus (IBV) by using a multi-fragment protein as coating antigen. RESULTS: A multi-fragment antigen, termed BE, which was composed of eight antigenic fragments selected from the three major proteins (S, M, and N) of IBV, was expressed in Escherichia coli. The entire protein had a molecular weight of 61.5 kDa. In addition to it, a smaller truncated protein was also produced; both could react with IBV-positive serum. Next, an indirect ELISA (BE-ELISA) was developed. Coefficients of variation of this assay were lower than 10 %, and no cross-reactivity between the coated antigen BE and antiserum against newcastle disease virus, avian influenza virus, or infectious bursal disease virus was observed. The performance of BE-ELISA was evaluated, and showed 95.4 % coincidence ratio with the whole virus based-ELISA (IDEXX). CONCLUSIONS: The multi-fragment antigen (BE) may represent a promising alternative to the whole virus without safety problems, and this newly established ELISA provides an effective method for anti-IBV antibody detection. PMID- 26272398 TI - Blocking Endogenous Leukemia Inhibitory Factor During Placental Development in Mice Leads to Abnormal Placentation and Pregnancy Loss. AB - The placenta forms the interface between the maternal and fetal circulation and is critical for the establishment of a healthy pregnancy. Specialized trophoblast cells derived from the embryonic trophectoderm play a pivotal role in the establishment of the placenta. Leukemia inhibitory factor (LIF) is one of the predominant cytokines present in the placenta during early pregnancy. LIF has been shown to regulate trophoblast adhesion and invasion in vitro, however its precise role in vivo is unknown. We hypothesized that LIF would be required for normal placental development in mice. LIF and LIFRalpha were immunolocalized to placental trophoblasts and fetal vessels in mouse implantation sites during mid gestation. Temporally blocking LIF action during specific periods of placental development via intraperitoneal administration of our specific LIFRalpha antagonist, PEGLA, resulted in abnormal placental trophoblast and vascular morphology and reduced activated STAT3 but not ERK. Numerous genes regulating angiogenesis and oxidative stress were altered in the placenta in response to LIF inhibition. Pregnancy viability was also significantly compromised in PEGLA treated mice. Our data suggest that LIF plays an important role in placentation in vivo and the maintenance of healthy pregnancy. PMID- 26272399 TI - Overshadowing and latent inhibition in nausea-based context conditioning in humans: Theoretical and practical implications. AB - Volunteer participants underwent nausea-inducing body rotation in a distinctive context, and the acquired ability of the contextual cues to evoke nausea was subsequently assessed by a symptom rating scale. One group received prior exposure to the context (a latent inhibition procedure); a second consumed a novel flavour prior to rotation (an overshadowing procedure); a third group experienced both procedures; and a control group received neither. When tested in the context in the absence of rotation, all groups reported an increase in nausea related symptoms at the time when rotation had previously occurred, an outcome consistent with the occurrence of conditioned nausea. The magnitude of this increase did not differ across the groups, but the overall level of responsiveness (the degree to which nausea-related symptoms were reported) was enhanced in the latent inhibition and reduced in the overshadowing condition. Cortisol levels showed the same pattern. The implications of these findings for the proposal that overshadowing and latent inhibition procedures might be used to control the development of anticipatory nausea in patients undergoing chemotherapy is considered. PMID- 26272400 TI - Antimicrobials: Novel antibodies defeat dengue virus. PMID- 26272401 TI - Microbial ecology: Sorting out viral dark matter. PMID- 26272411 TI - Use of Mobile Clinical Decision Support Software by Junior Doctors at a UK Teaching Hospital: Identification and Evaluation of Barriers to Engagement. AB - BACKGROUND: Clinical decision support (CDS) tools improve clinical diagnostic decision making and patient safety. The availability of CDS to health care professionals has grown in line with the increased prevalence of apps and smart mobile devices. Despite these benefits, patients may have safety concerns about the use of mobile devices around medical equipment. OBJECTIVE: This research explored the engagement of junior doctors (JDs) with CDS and the perceptions of patients about their use. There were three objectives for this research: (1) to measure the actual usage of CDS tools on mobile devices (mCDS) by JDs, (2) to explore the perceptions of JDs about the drivers and barriers to using mCDS, and (3) to explore the perceptions of patients about the use of mCDS. METHODS: This study used a mixed-methods approach to study the engagement of JDs with CDS accessed through mobile devices. Usage data were collected on the number of interactions by JDs with mCDS. The perceived drivers and barriers for JDs to using CDS were then explored by interviews. Finally, these findings were contrasted with the perception of patients about the use of mCDS by JDs. RESULTS: Nine of the 16 JDs made a total of 142 recorded interactions with the mCDS over a 4-month period. Only 27 of the 114 interactions (24%) that could be categorized as on-shift or off-shift occurred on-shift. Eight individual, institutional, and cultural barriers to engagement emerged from interviews with the user group. In contrast to reported cautions and concerns about the impact of clinicians' use of mobile phone on patient health and safety, patients had positive perceptions about the use of mCDS. CONCLUSIONS: Patients reported positive perceptions toward mCDS. The usage of mCDS to support clinical decision making was considered to be positive as part of everyday clinical practice. The degree of engagement was found to be limited due to a number of individual, institutional, and cultural barriers. The majority of mCDS engagement occurred outside of the workplace. Further research is required to verify these findings and assess their implications for future policy and practice. PMID- 26272409 TI - Sexual development in Plasmodium parasites: knowing when it's time to commit. AB - Malaria is a devastating infectious disease that is caused by blood-borne apicomplexan parasites of the genus Plasmodium. These pathogens have a complex lifecycle, which includes development in the anopheline mosquito vector and in the liver and red blood cells of mammalian hosts, a process which takes days to weeks, depending on the Plasmodium species. Productive transmission between the mammalian host and the mosquito requires transitioning between asexual and sexual forms of the parasite. Blood- stage parasites replicate cyclically and are mostly asexual, although a small fraction of these convert into male and female sexual forms (gametocytes) in each reproductive cycle. Despite many years of investigation, the molecular processes that elicit sexual differentiation have remained largely unknown. In this Review, we highlight several important recent discoveries that have identified epigenetic factors and specific transcriptional regulators of gametocyte commitment and development, providing crucial insights into this obligate cellular differentiation process. PMID- 26272410 TI - Screening adherence and cancer risk perceptions in colorectal cancer survivors with Lynch-like syndrome. AB - Cancer screening recommendations for patients with Lynch-like syndrome (LLS) are not well defined. We evaluated adherence to Lynch syndrome (LS) screening recommendations, cancer risk perceptions, and communication within the families among colorectal cancer (CRC) survivors with LLS. Thirty-four participants with LLS completed a questionnaire about risk perception, adherence to LS screening recommendations, and communication with relatives. Clinical data were obtained from medical records. Most participants (76%) believed they should undergo colonoscopy every 1-2 years. Only 41% correctly interpreted their genetic tests as uninformative negative or as variant of unknown significance for LS. Less than half had had an upper gastrointestinal endoscopy for screening purpose. Among female participants, 86% had been screened for endometrial cancer (EC) and 71% for ovarian cancer. Most participants had informed relatives about the CRC diagnosis and advised them to undergo CRC screening, but only 50% advised female relatives to be screened for EC and only one-third advised relatives to have genetic counseling. Most CRC survivors with LLS follow the same cancer screening recommended for LS patients but do not understand the meaning of LLS. Greater care must be devoted to communicating the implications of nondiagnostic germline mutation testing among patients with LLS. PMID- 26272408 TI - Staphylococcal manipulation of host immune responses. AB - Staphylococcus aureus, a bacterial commensal of the human nares and skin, is a frequent cause of soft tissue and bloodstream infections. A hallmark of staphylococcal infections is their frequent recurrence, even when treated with antibiotics and surgical intervention, which demonstrates the bacterium's ability to manipulate innate and adaptive immune responses. In this Review, we highlight how S. aureus virulence factors inhibit complement activation, block and destroy phagocytic cells and modify host B cell and T cell responses, and we discuss how these insights might be useful for the development of novel therapies against infections with antibiotic resistant strains such as methicillin-resistant S. aureus. PMID- 26272412 TI - Can performance on summative evaluation of wax-added dental anatomy projects be better predicted from the combination of supervised and unsupervised practice than from supervised practice alone? AB - PURPOSE: The study explored the effects of adding student-directed projects in pre-clinical dental anatomy laboratory on improving the predictability of students' eventual performance on summative evaluation exercises, given the presence of intervening faculty-controlled, in-class practice. METHOD: All students from four consecutive classes (n = 555) completed wax-added home projects (HP), spending as much or as little time as desired and receiving no faculty feedback; followed by similar laboratory projects (LP) with time limits and feedback; and then summative practical projects (PP) in a timed format but without faculty feedback. Path analysis was used to assess if the student directed HP had any effect over and above the laboratory projects. RESULTS: Average scores were HP = 0.785 (SD = 0.089); LP = 0.736 (SD = 0.092); and PP = 0.743 (SD = 0.108). Path analysis was applied to show the effects of including a student-controlled home practice exercise on summative exercise performance. HP contributed 57% direct effect and 37% mediated effect through the LP condition. CONCLUSION: Student-directed home practice provided a measureable improvement in ability to predict eventual performance in summative test cases over and above the predictive contribution of intervening faculty-controlled practice conditions. PMID- 26272413 TI - Impact of cigarette smoking on the middle meatus microbiome in health and chronic rhinosinusitis. AB - BACKGROUND: Although cigarette smoking aggravates chronic rhinosinusitis (CRS), a detailed examination of the sinus microbiota in CRS and its clinical subtypes has yet to be performed in relation to history of smoking. Consequently, we examined associations between smoking history and sinonasal microbiome alterations in both CRS and non-CRS populations. METHODS: Middle meatus swabs collected during endoscopic sinus surgery were analyzed by analysis of 16S ribosomal RNA (rRNA) sequences. Multiple analysis of variance tests were performed to determine whether microbiome composition varied with smoking history and other clinical/demographic covariates associated with CRS subtypes. RESULTS: A total 70 CRS patients and 31 control subjects were analyzed. In a univariate analysis, smoking (p = 0.04), preoperative antibiotics (p = 0.03), and purulence (p = 0.0002) were significantly associated with the genus-level composition of the middle meatus microbiota. When included in a multivariable model, smoking was found to have significant interactions with CRS (p = 0.02), polyposis (p = 0.03), purulence (p = 0.0004), and use of saline rinses (p = 0.05). Diverse bacterial taxa differed significantly in abundance between never-smokers and current/former smokers, as well as between different CRS subtypes. CONCLUSION: Substantial changes in sinus bacterial colonization were observed in smokers and nonsmokers. Although the microbiota of both CRS and non-CRS subjects were altered with smoking history, different bacterial taxa were affected by smoking in the 2 patient groups. Thus, the effects of smoking on the sinus microbiota are likely to be modified by physiological and immunological functions of the underlying sinus mucosa. PMID- 26272414 TI - Factors influencing food preparation behaviours: findings from focus groups with Mexican-American mothers in southern California. AB - OBJECTIVE: The purpose of the present study was to explore food preparation behaviours, attitudes, meal planning and shopping among Mexican-American mothers. DESIGN: Data were collected through four focus groups with mothers of Mexican origin/ancestry who considered themselves to be the primary food preparer. Topics included food preparation behaviours and influencers (culture, family, attitudes, barriers, meal planning and shopping). Data were analysed using a qualitative grounded theory approach. All focus groups were audio recorded, transcribed verbatim and coded for themes. SETTING: Data were collected in southern California, USA in 2013. SUBJECTS: Of the sample of twenty-one Mexican-American mothers, thirteen were born outside the USA and the mean household size was five members. RESULTS: Participants reported that food was often prepared using traditional staples and food preparation behaviours were learned from maternal family members. Participants also suggested that health was influenced by foods eaten and how they were prepared. Salient factors influencing food preparation behaviours included culture and tradition, maternal family members' food preparation behaviours, food preparation self-efficacy and attitudes towards healthy eating. Time and busy schedules were cited as barriers. CONCLUSIONS: Future interventions should consider utilizing family-based approaches and teaching culturally relevant food preparation skills, especially to youth, while reinforcing more healthful dietary practices. PMID- 26272415 TI - Extracellular production of Pseudozyma (Candida) antarctica lipase B with genuine primary sequence in recombinant Escherichia coli. AB - An Escherichia coli expression system was established to produce recombinant extracellular Pseudozyma (Candida) antarctica lipase B (CALB). With the aim of producing the genuine CALB without additional amino acid residues, the mature portion of the CALB gene was fused seamlessly to a pelB signal sequence and expressed in E. coli BL21(DE3) using the pET system. Inducing gene expression at low temperature (20 degrees C) was crucial for the production of active CALB; higher temperatures caused inclusion body formation. Prolonged induction for 48 h at 20 degrees C allowed for the enzyme to be released into the culture medium, with more than half of the activity detected in the culture supernatant. A catalytically inactive CALB mutant (S105A) protein was similarly released, suggesting that the lipid-hydrolyzing activity of the enzyme was not the reason for the release. The CALB production level was further improved by optimizing the culture medium. Under the optimized conditions, the CALB in the culture supernatant amounted to 550 mg/L. The recombinant CALB was purified from the culture supernatant, yielding 5.67 mg of purified CALB from 50 mL of culture. N terminal sequencing and ESI-MS analyses showed proper removal of the pelB signal sequence and the correct molecular weight of the protein, respectively, confirming the structural integrity of the recombinant CALB. The kinetic parameters towards p-nitrophenylbutyrate and the enantiomeric selectivity on rac 1-phenylethylacetate of the recombinant CALB were consistent with those of the authentic CALB. This is the first example of E. coli-based extracellular production of a CALB enzyme without extra amino acid residues. PMID- 26272416 TI - TORC1 activity is partially reduced under nitrogen starvation conditions in sake yeast Kyokai no. 7, Saccharomyces cerevisiae. AB - Industrial yeasts are generally unable to sporulate but treatment with the immunosuppressive drug rapamycin restores this ability in a sake yeast strain Kyokai no. 7 (K7), Saccharomyces cerevisiae. This finding suggests that TORC1 is active under sporulation conditions. Here, using a reporter gene assay, Northern and Western blots, we tried to gain insight into how TORC1 function under nitrogen starvation conditions in K7 cells. Similarly to a laboratory strain, RPS26A transcription was repressed and Npr1 was dephosphorylated in K7 cells, indicative of the expected loss of TORC1 function under nitrogen starvation. The expression of nitrogen catabolite repression-sensitive genes, however, was not induced, the level of Cln3 remained constant, and autophagy was more slowly induced than in a laboratory strain, all suggestive of active TORC1. We conclude that TORC1 activity is partially reduced under nitrogen starvation conditions in K7 cells. PMID- 26272417 TI - Correction: Understanding metal homeostasis in primary cultured neurons. Studies using single neuron subcellular and quantitative metallomics. AB - Correction for 'Understanding metal homeostasis in primary cultured neurons. Studies using single neuron subcellular and quantitative metallomics' by Robert A. Colvin et al., Metallomics, 2015, 7, 1111-1123. PMID- 26272418 TI - Repetitive transcranial magnetic stimulation and transcranial direct current stimulation in motor rehabilitation after stroke: an update. AB - Stroke is a leading cause of adult motor disability. The number of stroke survivors is increasing in industrialized countries, and despite available treatments used in rehabilitation, the recovery of motor functions after stroke is often incomplete. Studies in the 1980s showed that non-invasive brain stimulation (mainly repetitive transcranial magnetic stimulation [rTMS] and transcranial direct current stimulation [tDCS]) could modulate cortical excitability and induce plasticity in healthy humans. These findings have opened the way to the therapeutic use of the 2 techniques for stroke. The mechanisms underlying the cortical effect of rTMS and tDCS differ. This paper summarizes data obtained in healthy subjects and gives a general review of the use of rTMS and tDCS in stroke patients with altered motor functions. From 1988 to 2012, approximately 1400 publications were devoted to the study of non-invasive brain stimulation in humans. However, for stroke patients with limb motor deficit, only 141 publications have been devoted to the effects of rTMS and 132 to those of tDCS. The Cochrane review devoted to the effects of rTMS found 19 randomized controlled trials involving 588 patients, and that devoted to tDCS found 18 randomized controlled trials involving 450 patients. Without doubt, rTMS and tDCS contribute to physiological and pathophysiological studies in motor control. However, despite the increasing number of studies devoted to the possible therapeutic use of non-invasive brain stimulation to improve motor recovery after stroke, further studies will be necessary to specify their use in rehabilitation. PMID- 26272419 TI - Acquired spatial dyslexia. AB - Acquired spatial dyslexia is a reading disorder frequently occurring after left or right posterior brain lesions. This article describes several types of spatial dyslexia with an attentional approach. After right posterior lesions, patients show left neglect dyslexia with errors on the left side of text, words, and non words. The deficit is frequently associated with left unilateral spatial neglect. Severe left neglect dyslexia can be detected with unlimited exposure duration of words or non-words. Minor neglect dyslexia is detected with brief presentation of bilateral words, one in the left and one in the right visual field (phenomenon of contralesional extinction). Neglect dyslexia can be explained as a difficulty in orienting attention to the left side of verbal stimuli. With left posterior lesions, spatial dyslexia is also frequent but multiform. Right neglect dyslexia is frequent, but right unilateral spatial neglect is rare. Attentional dyslexia represents difficulty in selecting a stimulus, letter or word among other similar stimuli; it is a deficit of attentional selection, and the left hemisphere plays a crucial role in selection. Two other types of spatial dyslexia can be found after left posterior lesions: paradoxical ipsilesional extinction and stimulus centred neglect dyslexia. Disconnections between left or right parietal attentional areas and the left temporal visual word form area could explain these deficits. Overall, a model of attention dissociating modulation, selection control, and selection positioning can help in understanding these reading disorders. PMID- 26272420 TI - Lentiviral shRNA against KCa3.1 inhibits allergic response in allergic rhinitis and suppresses mast cell activity via PI3K/AKT signaling pathway. AB - Calcium-activated potassium ion channel-3.1 (KCa3.1) plays a pivotal role in the potassium-calcium exchange involved in atopy. This study aimed to explore the impact of lentiviral-mediated shRNA silencing KCa3.1 on allergic response in a murine allergic rhinitis (AR) model. The BALB/c mice were divided into four groups: untreated AR group, negative control AR group, lentiviral KCa3.1-shRNA treated AR group and normal control group. Concentrations of ovalbumin (OVA) specific IgE, histamine and leukotrienes C4 (LTC4) in serum, and IL-4, IL-9 and IL-17 in nasal lavage fluid (NLF) were analyzed. Goblet cells and mast cells were counted. KCa3.1 positive cells were counted after immunolabelling by immunofluorescence method. KCa3.1, Mucin 5AC (MUC5AC), and tryptase mRNA levels were determined using real-time polymerase chain reaction. Furthermore, P815 cell line was used to explore the role and mechanism of lentiviral KCa3.1-shRNA on mast cells. The results showed that LV-KCa3.1-shRNA intervention effectively attenuated allergic responses in LV-KCa3.1-shRNA treated mice. LV-KCa3.1-shRNA intervention effectively suppressed KCa3.1 levels and phosphorylation of AKT in P815 cells, leading to the downregulation of tryptase, IL-6 and IL-8 levels. LV KCa3.1-shRNA intervention effectively attenuated the allergic responses in AR and suppressed mast cell activity by inhibiting PI3K/AKT signaling pathway. PMID- 26272421 TI - An Unusual Case of Chronic Abdominal Pain. PMID- 26272422 TI - A Case of Proton Pump Inhibitor-Resistant Multiple Gastric Ulcers Caused by Eosinophilic Gastroenteritis. PMID- 26272423 TI - [Hemangiolymphangioma of the spermatic cord in a 17 year-old: A case report]. AB - BACKGROUND: Hemangiolymphangiomas are extremely rare tumours arising from blood and lymphatic vessels. It is a benign disorder, and 95% are of the neck and axilla. OBJECTIVE: To present a case of hemangiolymphangioma of the spermatic cord with contralateral recurrence. CLINICAL CASE: A 17-year-old patient with a progressively growing tumour in the right inguinoscrotal region. Examination revealed a painless, movable and soft right inguinoscrotal tumour, mobile and soft. Surgical resection showed a 25*25cm tumour from spermatic cord, right testicle, and subcutaneous cellular tissue. Histopathological study reported a hemangiolymphangioma. CONCLUSIONS: The spermatic cord is an unusual location of hemangiolymphangiomas with contralateral recurrence. Surgical treatment, with histopathological diagnosis, is associated with good prognosis. PMID- 26272424 TI - [Acute abdomen with actinomycosis of the colon: A case report]. AB - BACKGROUND: Actinomyces infection is a chronic inflammatory process that can sometimes, clinically and radiographically, closely mimic a malignant tumour, which may lead to giving a delayed or inappropriate treatment. CLINICAL CASE: Male 41 years old, with no previous history, with abdominal pain of one month onset, as well as weight loss, intermittent fever and diarrhoea. He developed acute abdomen and underwent surgery, finding a tumour in the distal ileum with necrosis and punctiform perforations. A resection was performed on the affected part of the ileum and colon, as well as an ileostomy using Hartmann's procedure. CONCLUSIONS: Actinomycosis is a disease that must be considered by the surgeon when faced with a clinical picture of subacute onset with intermittent fever, weight loss, abdominal pain, and even anaemia in patients with abdominal and retroperitoneal abscesses or previous history of surgery. PMID- 26272425 TI - [Clear cell adenocarcinoma arising from abdominal wall endometriosis]. AB - BACKGROUND: Clear cell carcinoma originating in the abdominal wall is a rare event. It is generally associated with endometrial tissue implants left behind after a caesarean section or other gynaecological operations. Its pathophysiology is complex and controversial. CLINICAL CASE: The case is presented of a 45 year old female with history of three caesarean sections, who was seen due to having a tumour mass of 6 months onset in the anterior abdominal wall. Imaging studies confirmed its location, and due to measuring 9 by 7 cm it was suspected to be an urachal tumour. A resection with wide margins was performed. The histopathology report was of a clear cell adenocarcinoma originated in ectopic endometrial tissue, with negative margins. CONCLUSION: This is a very rare case, with few cases reported in the literature. This diagnosis should be included in tumours of the abdominal wall. PMID- 26272426 TI - Conjunctival and corneal sensitivity in patients under topical antiglaucoma treatment. AB - The purpose of the study is to measure corneal and conjunctival sensitivity in patients under glaucoma topical treatment as compared to a control group. It is a case-control study. Corneal and conjunctival esthesiometry were carried out through a Cochet-Bonnet esthesiometer. We took healthy individuals as controls, who did not use any type of ophthalmic topical medications and without history of ocular surface pathology or irritation. The study group was subdivided per number of applications (1, 2, and 3 or more applications). From a total 182 eyes from 91 patients, of which 26 (28.57 %) were controls and 65 (71.43 %) were in the study group, a mean corneal sensitivity of 58.98 +/- 2.25 mm was found in the control group and 52.97 +/- 6.41 mm in patients using topical medication. Mean conjunctival sensitivity was 18.80 +/- 5.40 mm in the control group and 11.76 +/- 5.45 mm in the study group. There was no statistically significant difference among groups when separated by 1, 2, and 3 or more applications. Eyes under use of timolol-containing medications showed lower sensitivity values as compared to other topical antiglaucoma medications. Corneal and conjunctival sensitivities are diminished in patients with chronic use of topical hypotensive medications and these results can explain the lack of correlation between signs and symptoms that is typically found in patients treated for glaucoma or ocular hypertension. PMID- 26272427 TI - Atrasentan in Patients With Advanced Renal Cell Carcinoma: A Phase 2 Trial of the ECOG-ACRIN Cancer Research Group (E6800). AB - BACKGROUND: Atrasentan, an oral endothelin receptor A antagonist, demonstrated phase 1 activity in patients with renal cell carcinoma (RCC). A phase 2 study was undertaken in patients with measurable or bone-only metastatic RCC in the pre VEGF/TKI era. METHODS AND MATERIALS: Patients were stratified by disease status and prior immunotherapy. Eligible patients had no prior chemotherapy, 0 to 1 prior immunotherapies, and an Eastern Cooperative Oncology Group performance status of 0 to 2. Patients received atrasentan 10 mg per day until progression. The primary end point was progression-free (PF) rate at 6 months. Rates of 25% among patients treated with prior immunotherapy and 45% among patients with no prior immunotherapy were considered promising. A 2-stage design was used for cohorts without prior immunotherapy. RESULTS: From 2003 to 2005, 98 patients were registered. Median treatment duration was 9.9 weeks (range, 0.3-107 weeks). Toxicities were mild; 71% of patients reported no grade 3 or higher treatment related events. Grade 4 events included neutropenia (n = 3), dyspnea (n = 2), thrombosis (n = 1), and arrhythmia (n = 1). Two grade 5 events (dyspnea and constitutional) were possibly treatment related. Six-month PF rates (90% confidence interval) were 14% (6-25), 0% (0-39), 8% (1-23), and 22% (8-44), respectively, for patients with prior immunotherapy/measurable disease (n = 44), prior immunotherapy/bone metastases (n = 6), no prior immunotherapy/measurable disease (n = 25), and no prior immunotherapy/bone metastases (n = 18). Median PF survival was 2.3 months (95% confidence interval, 2.0-3.5 months). CONCLUSION: Although well tolerated, atrasentan did not yield 6-month PF rates supporting its use as first-line monotherapy in patients with advanced RCC. PMID- 26272428 TI - Stereoselective Bioreduction of alpha-Azido Ketones by Whole Cells of Marine Derived Fungi. AB - Seven strains of marine-derived fungi (Aspergillus sclerotiorum CBMAI 849, Cladosporium cladosporioides CBMAI 857, Penicillium raistrickii CBMAI 931, Penicillium citrinum CBMA 1186, Mucor racemosus CBMAI 847, Beauveria felina CBMAI 738, and Penicillium oxalicum CBMAI 1185) and terrestrial fungus Penicillium chrysogenum CBMA1199 were screened as catalysts for the asymmetric reduction of alpha-keto azides 5-8 to their corresponding beta-azidophenylethanols 9-12. The marine fungi showed Prelog and anti-Prelog selectivities to the reduction alpha keto azides 5-8. The fungi A. sclerotiorum CBMAI 849, C. cladosporioides CBMAI 857, P. raistrickii CBMAI 931, and P. citrinum CBMA 1186 catalyzed the reduction of azido ketone 6 to the corresponding (R)-2-azido-1-(4-methoxyphenyl)ethanol (10) with good conversions (68-100 %) and excellent enantiomeric excesses (>99 % ee) according to Prelog rule. PMID- 26272429 TI - Identification, Phylogeny, and Function of fabp2 Paralogs in Two Non-Model Teleost Fish Species. AB - Intestinal fatty-acid-binding protein (IFABP or FABP2) is a cytosolic transporter of long-chain fatty acids, which is mainly expressed in cells of intestinal tissue. Fatty acids in teleosts are an important source of energy for growth, reproduction, and swimming and a main ingredient in the yolk sac of embryos and larvae. The fabp2 paralogs, fabp2a and fabp2b, were identified for 26 teleost fish species including the paralogs for the two non-model teleost fish species, namely the gilthead sea bream (Sparus aurata) and the European sea bass (Dicentrarchus labrax). Despite the high similarity of fabp2 paralogs, as well as the identical organization in four exons, paralogs were mapped to different chromosomes/linkage groups supporting the hypothesis that the identified transcripts are true paralogs originating from a single ancestor gene after genome duplication. This was also confirmed by phylogenetic analysis using fabp2 sequences of 26 teleosts and by synteny analysis carried out with ten teleosts. Differential expression analysis of the gilthead sea bream and European sea bass fabp2 paralogs in the intestine after fasting and refeeding experiment further revealed their altered implication in metabolism. Additional expression studies in seven developmental stages of the two species detected fabp2 paralogs relatively early in the embryonic development as well as possible complementary or separated roles of the paralogs. The identification and characterization of the two fabp2 paralogs will contribute significantly to the understanding of the fabp2 evolution as well as of the divergences in fatty acid metabolism. PMID- 26272430 TI - Omega-3 DHA- and EPA-dopamine conjugates induce PPARgamma-dependent breast cancer cell death through autophagy and apoptosis. AB - BACKGROUND: The omega-3 docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) may form conjugates with amines that have potential health benefits against common diseases including cancers. Here we synthesized DHA-dopamine (DHADA) and EPA-dopamine (EPADA) conjugates and studied their biological effects on different breast cancer cell lines. METHODS AND RESULTS: MTT assays indicated that increasing concentrations of DHADA and EPADA significantly affected viability in MCF-7, SKBR3 and MDA-MB-231 breast cancer cells, whereas no effect was observed in MCF-10A non-tumorigenic epithelial breast cells. DHADA and EPADA enhanced Beclin-1 expression, as evidenced by immunoblotting, real-time-PCR and functional analyses. Chromatin Immunoprecipitation (ChIP) and Re-ChIP assays revealed that both compounds induced recruitment of Peroxisome-Proliferator-Activated-Receptor gamma (PPARgamma) and RNA Polymerase-II at the Retinoic-X-Receptor binding region on Beclin-1 promoter. Moreover, both compounds enhanced autophagosome formation, evaluated by LC-3 and monodansylcadaverine labeling, that was prevented by the PPARgamma antagonist GW9662, addressing the direct involvement of PPARgamma. Noteworthy, long-term treatment with DHADA and EPADA caused the blockade of autophagic flux followed by apoptotic cell death as evidenced by PARP cleavage and DNA fragmentation in all breast cancer cells. CONCLUSIONS: We have provided new insights into the molecular mechanism through which PPARgamma, as a central molecule in the cross talk between autophagy and apoptosis, mediates DHADA- and EPADA-induced cell death in breast cancer cells. GENERAL SIGNIFICANCE: Our findings suggest that omega-3 DHADA- and EPADA activation of PPARgamma may assume biological relevance in setting novel adjuvant therapeutic interventions in breast carcinoma. PMID- 26272431 TI - H2S-induced S-sulfhydration of pyruvate carboxylase contributes to gluconeogenesis in liver cells. AB - BACKGROUND: Cystathionine gamma-lyase (CSE)-derived hydrogen sulfide (H(2)S) possesses diverse roles in the liver, affecting lipoprotein synthesis, insulin sensitivity, and mitochondrial biogenesis. H(2)S S-sulfhydration is now proposed as a major mechanism for H(2)S-mediated signaling. Pyruvate carboxylase (PC) is an important enzyme for gluconeogenesis. S-sulfhydration regulation of PC by H(2)S and its implication in gluconeogenesis in the liver have been unknown. METHODS: Gene expressions were analyzed by real-time PCR and western blotting, and protein S-sulfhydration was assessed by both modified biotin switch assay and tag switch assay. Glucose production and PC activity was measured with coupled enzyme assays, respectively. RESULTS: Exogenously applied H(2)S stimulates PC activity and gluconeogenesis in both HepG2 cells and mouse primary liver cells. CSE overexpression enhanced but CSE knockout reduced PC activity and gluconeogenesis in liver cells, and blockage of PC activity abolished H(2)S induced gluconeogenesis. H(2)S had no effect on the expressions of PC mRNA and protein, while H(2)S S-sulfhydrated PC in a dithiothreitol-sensitive way. PC S sulfhydration was significantly strengthened by CSE overexpression but attenuated by CSE knockout, suggesting that H(2)S enhances glucose production through S sulfhydrating PC. Mutation of cysteine 265 in human PC diminished H(2)S-induced PC S-sulfhydration and activity. In addition, high-fat diet feeding of mice decreased both CSE expression and PC S-sulfhydration in the liver, while glucose deprivation of HepG2 cells stimulated CSE expression. CONCLUSIONS: CSE/H(2)S pathway plays an important role in the regulation of glucose production through S sulfhydrating PC in the liver. GENERAL SIGNIFICANCE: Tissue-specific regulation of CSE/H(2)S pathway might be a promising therapeutic target of diabetes and other metabolic syndromes. PMID- 26272432 TI - On the physics of the emergence of sensorimotor control in the absence of the brain. AB - The evolutionary origin of sensorimotor control requires a sort of physical durability, other than Galilean inertia being accessible in third-person description in the present tense. One candidate to address this need is the 'class property' of a material body's durability remaining invariant during the exchange of component elements. Using grammatical tense as a descriptive attribute, this durability is accessible only in the frequent update of the present perfect tense in the present progressive tense at the 'now' of the present moment. In this view, the update of the perfect tense is equated with the onset and occurrence of on/off switching behavior of physical origin underlying the phenomena of sensorimotor control. Notably, the physical update of the perfect tense is specific only to the 'now and here' that is central in the tradition of phenomenology. The phenomena upholding thermodynamics, when taken apart from its theory, are decisive in facilitating the onset of sensorimotor control. Instrumental to the emergence of both life in general and sensorimotor control in particular may be the occurrence of a 'physical and chemical affinity' of the material bodies of whatever type. Such will let the constant exchange of component elements be feasible, so that the class identity equipped with the capacity for measurement is made available within the phenomenon. Material bodies constantly exchanging such component elements would make the material world open to biology by allowing each element to experience the organizational whole from within. The internal observer responsible for the origins of life may do double duty of letting itself be durable on the material basis while observing the conditions making it durable on the linguistic ground. The origins of life appear to us a material phenomenon when they are approached with use of our linguistic tools that can get rid of the strict stipulation of an abstract nature applied to the description of dynamical laws in physics. PMID- 26272433 TI - The Microbiome and Osteosarcopenic Obesity in Older Individuals in Long-Term Care Facilities. AB - Increasing evidence points to a role of altered microbiota on inflammation, obesity, and other chronic conditions. This commentary addresses the connection between osteosarcopenic obesity syndrome, an impairment in bone, muscle, and adipose tissues that occurs concurrently, with the altered microbiota in elderly individuals, particularly those living in long-term care facilities. As elderly move to long-term care facilities, they experience changes in gut bacteria that might exasperate the underlying conditions such as osteosarcopenic obesity. These individuals have exponentially higher osteoporotic fracture rates and immobility impairments compared to independently living individuals. However, there is very limited research on this topic and more insight is needed on the impact of probiotic treatment and diet in older individuals, especially those with chronic conditions related to aging, such as osteosarcopenic obesity. PMID- 26272434 TI - Manual small incision extracapsular cataract surgery in Australia: response. PMID- 26272435 TI - Within- and between-herd prevalence variation of Mycobacterium avium subsp. paratuberculosis infection among control programme herds in Denmark (2011-2013). AB - This study aimed to estimate the between- (HTP) and within- (TP) herd true prevalence distribution of Mycobacterium avium subsp. paratuberculosis (MAP) infection in dairy cattle herds participating in the Danish MAP control programme. All herds enrolled in the programme between 2011 and 2013 were included in the analysis, and one annual milk-ELISA test of all lactating cows present in such herds was considered. A Bayesian latent class model was used to obtain HTP and TP posterior distributions for each year. The model adjusts for uncertainty in age-specific test sensitivity and prior prevalence estimates. Bayesian posterior probabilities were computed in order to compare prevalence between the years. A total of 665,700 samples were included in the study, from 221,914, 224,040, and 220,466 cows sourced from 1138, 1112, and 1059 herds in years 2011, 2012, and 2013, respectively. In that period, HTP estimates of 0.92 (95% posterior probability interval (PPI), 0.87-0.96), 0.78 (95% PPI, 0.74-0.83), and 0.75 (95% PPI, 0.71-0.78) were recorded, respectively. Low TP were observed, with population mean estimates of 0.08 (95% PPI, 0.07-0.08), 0.07 (95% PPI, 0.07 0.08), and 0.07 (95% PPI, 0.06-0.07) for the three consecutive years. Statistically-important differences were recorded for HTP and population mean TP estimates between years, indicating a trend for a decreasing level of MAP infection at both herd and animal level. Model results showed that MAP infection was widespread among the Dairy cattle herds participating in the Danish control programme, though in general it was kept at very low levels. PMID- 26272436 TI - Structural insights into the benzophenanthridines binding to human glycine transporter GlyT1. AB - We previously identified cysteine 475 as a key residue for the inhibitory action of sanguinarine on the human glycine transporter GlyT1c. To define potential benzophenanthridine binding pocket more closely, we created a structural homology model of GlyT1 and also mutated several amino acids in the vicinity of cysteine 475. Even though this area contains the molecular determinants of the glycine and sodium permeation pathways, and several mutations resulted in an inactive transporter, we found that the mutation of a polar aromatic tyrosine 370 to purely aromatic phenylalanine, but not to an aliphatic leucine, significantly increased the sensitivity of GlyT1 to both sanguinarine and chelerythrine. The reduction of sanguinarine to dihydrosanguinarine completely eliminated the alkaloid's inhibitory potency. Both these results suggest that aromaticity is important in the interaction of benzophenanthridines with GlyT1. Even though tyrosine 370 is part of the conformationaly highly flexible glycine binding site, and is accesible during the transport process from both intra and extracellular sites, the cytoplasmic location of the second alkaloid sensitive residue, cysteine 475, suggests that the benzophenanthridines might attack the area of the GlyT1 intracellular gates. PMID- 26272437 TI - Coronary atherosclerosis and adverse outcomes in patients with recent-onset atrial fibrillation and troponin rise. AB - BACKGROUND: The relationship between troponin and atrial fibrillation (AF) without acute coronary syndrome is still unclear. We sought to investigate the presence of coronary atherosclerosis and adverse outcomes in patients with AF. METHODS: Consecutive patients with recent-onset AF and without severe comorbidities were enrolled between 2004 and 2013. Patients with a troponin rise or with adverse outcomes were considered for coronary angiography and revascularization when "critical" stenosis (>=70%) was recognized. Propensity score matching was performed to adjust for baseline characteristics; after matching, no differences existed between the groups of patients with or without troponin rise. The primary end point was the composite of acute coronary syndrome, revascularization, and cardiac death at 1- and 12-month follow-ups. RESULTS: Of 3627 patients enrolled, 3541 completed the study; 202 (6%) showed troponin rise; and 91 (3%), an adverse outcome. In the entire cohort, on multivariate analysis, the odds ratio for the occurrence of the primary end point of troponin rise was 14 (95% confidence interval [CI], 10-23; P<.001), and that of known coronary artery disease was 3 (CI, 2-5; P=.001). In the matching cohort, the odds ratio of troponin rise was 10 (CI, 4-22; P<.001), and that of TIMI score greater than 2 was 4 (CI, 2-9; P<=.001). In the entire cohort, patients with or without troponin rise achieved the primary end point in 38 (19%) and 43 (1%) patients, respectively (P<.001). Stroke occurred in 4 (2%) and 20 (1%), respectively (P=.018). Critical stenosis and revascularization account for 23 (12%) and 15 (1%), respectively (P<.001). In the matching cohort, results were confirmed, but incidence of stroke was comparable. CONCLUSIONS: Patients with recent-onset AF and troponin rise showed higher prevalence of coronary atherosclerosis and adverse cardiac events. Stroke per se did not succeed in justifying the high morbidity. Thus, beyond stroke, coronary atherosclerosis might have a pivotal role in poor outcomes. PMID- 26272439 TI - Biomechanical behavior of plantar fat pad in healthy and degenerative foot conditions. AB - The plantar fat pad of the human foot is a specific tissue made up of adipose chambers enveloped by fibrous septa. Aging, pathology or trauma may affect its histo-morphological configuration and mechanical response. The correlation between histo-morphological configuration and mechanical properties is analyzed by a computational approach, aiming to identify the influence of degenerative phenomena on plantar fat pad mechanics. Finite element meso-models, as numerical model of an intermediate-length scale, are developed for healthy and degenerative conditions, considering the different properties that degenerative phenomena may affect, such as the adipose chambers dimension, the fibrous septa thickness, the fibers orientation and the sub-components mechanical behavior. Histo-morphometric data are analyzed to identify average configurations of the fat chambers and fibrous septa, while specific constitutive formulations are provided to define their mechanical response. Numerical analyses are performed to identify the stress-strain behavior of the plantar fat pad considering healthy and degenerative configurations. The results from meso-models are applied to identify the parameters of a phenomenological constitutive formulation that interprets the overall human fat pad tissue mechanics. The constitutive formulation is implemented within a 3D finite element model of the heel region that is applied to evaluate the influence of degenerative phenomena on the overall mechanical functionality of the foot. PMID- 26272440 TI - [Analysis of pacemaker ECGs]. AB - INTRODUCTION: The key to a successful analysis of a pacemaker electrocardiogram (ECG) is the application of the systematic approach used for any other ECG without a pacemaker: analysis of (1) basic rhythm and rate, (2) QRS axis, (3) PQ, QRS and QT intervals, (4) morphology of P waves, QRS, ST segments and T(U) waves and (5) the presence of arrhythmias. METHODS: If only the most obvious abnormality of a pacemaker ECG is considered, wrong conclusions can easily be drawn. If a systematic approach is skipped it may be overlooked that e.g. atrial pacing is ineffective, the left ventricle is paced instead of the right ventricle, pacing competes with intrinsic conduction or that the atrioventricular (AV) conduction time is programmed too long. Apart from this analysis, a pacemaker ECG which is not clear should be checked for the presence of arrhythmias (e.g. atrial fibrillation, atrial flutter, junctional escape rhythm and endless loop tachycardia), pacemaker malfunction (e.g. atrial or ventricular undersensing or oversensing, atrial or ventricular loss of capture) and activity of specific pacing algorithms, such as automatic mode switching, rate adaptation, AV delay modifying algorithms, reaction to premature ventricular contractions (PVC), safety window pacing, hysteresis and noise mode. CONCLUSION: A systematic analysis of the pacemaker ECG almost always allows a probable diagnosis of arrhythmias and malfunctions to be made, which can be confirmed by pacemaker control and can often be corrected at the touch of the right button to the patient's benefit. PMID- 26272438 TI - Effects of ethanol on systemic hemodynamics in a porcine model of accidental hypothermia. AB - OBJECTIVES: Accidental hypothermia is frequently associated with ethanol intoxication. Each has independent effects on systemic hemodynamics, but their combined effects are poorly understood. We aimed to describe the hemodynamic effects of ethanol intoxication in a model of severe hypothermia and rewarming. METHODS: Anesthetized pigs was assigned to control (n=8) or ethanol groups (ETOH) (n=7, 3 mg/kg of ethanol via an orogastric tube). Subjects were cooled to 25 degrees C using ice packs and then warmed to baseline core temperature with passive external and active core rewarming. RESULTS: In the ETOH group, peak serum ethanol concentration was 202 mg/dL at 25 degrees C. Ethanol had no effect on time of cooling or rewarming. In both the control and ETOH, there were similar maximal decreases in mean arterial pressure (from 94+/-24 to 50+/-15 mm Hg and 100+/-27 to 31+/-12 mm Hg, respectively), ventricular contractility (rate of maximal left ventricular pressure rise from 5731+/-1462 to 2610+/-596 mm Hg/s and 6832+/-1384 to 1937+/-437 mm Hg/s, respectively), and cardiac output (from 2.14+/ 0.8 to 0.53+/-0.3 L/min and 2.93+/-0.9, to 0.44+/-0.2 L/min, respectively; all P<.001). After rewarming, only in the ETOH group were persistent decreases in mean arterial pressure (59+/-14 mm Hg), contractility (3982+/-1573 mm Hg/s), and cardiac output (1.6+/-0.9 L/min, all P<.03) observed. CONCLUSIONS: Hypothermia caused significant adverse effects on cardiac function and systemic hemodynamics, which returned to baseline with rewarming. Ethanol intoxication had no additional effects on systemic hemodynamics during cooling; however, it caused more prolonged depression of cardiac function and adverse effects on systemic hemodynamics during rewarming. These data may have implications for resuscitation of ethanol-intoxicated victims of accidental hypothermia. PMID- 26272441 TI - [Localization of the origin of idiopathic ventricular extrasystoles and tachycardia from the outflow tract]. AB - Premature ventricular contractions (PVC) are a common cause for complaints. As a rule PVCs are not life-threatening if no structural heart disease is present; however, due to the symptoms treatment is often required using either antiarrhythmic drugs or more commonly catheter ablation. The surface electrocardiogram (ECG) is very helpful in localizing the origin of the arrhythmia, in particular for differentiating right from left ventricular sources. PMID- 26272443 TI - Intravitreal anti-vascular endothelial growth factor monotherapy for large submacular hemorrhage secondary to neovascular age-related macular degeneration. AB - PURPOSE: To evaluate the efficacy of anti-vascular endothelial growth factor (VEGF) monotherapy for large submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD). METHODS: A total of 49 treatment-naive patients (49 eyes) with large SMH (more than five disc areas (DAs)) secondary to nAMD were retrospectively included. All patients were treated with an initial series of 3 monthly intravitreal anti-VEGF injections, followed by as-needed injections. At the 12-month follow-up, changes in best-corrected visual acuity (BCVA), hemorrhage area, central foveal thickness, and development of vitreous hemorrhage after treatment were evaluated. RESULTS: The mean SMH area was 13.9 +/ 8.8 disk areas (DAs) and mean symptom duration was 7.25 +/- 5.9 days at baseline. The mean number of injections was 4.49 +/- 1.61. Twelve months after treatment, the mean BCVA significantly improved from 1.14 +/- 0.61 logarithm of the minimum angle of resolution (logMAR; 20/276, Snellen equivalent) to 0.82 +/- 0.53 logMAR (20/132; P = 0.002). Twenty-four eyes (49%) showed improvement of more than three lines of BCVA at 12 months after treatment. Baseline BCVA (odds ratio (OR), 5.119; 95% confidence interval (CI), 1.993-9.545; P = 0.004), duration of symptoms (OR, 0.727; 95% CI, 0.332-0.952; P = 0.024), hemorrhage area (OR, 0.892; 95% CI, 0.721-0.965; P = 0.011), and baseline central foveal thickness (OR, 0.881; 95% CI, 0.722-0.945; P = 0.032) were significantly associated with good visual acuity 12 months after treatment. CONCLUSIONS: Intravitreal anti-VEGF monotherapy is a valuable treatment option for large SMH secondary to nAMD. PMID- 26272442 TI - [Type of partner, socio-economic factors and risk practices in men who have sex with men]. AB - OBJECTIVE: Men who have sex with men (MSM) perform risk practices that pose a challenge to prevention strategies. The aim of this study was to analyse the association between receptive and insertive unprotected anal intercourse (RUAI and IUAI) according to the type of partner and the practice of barebacking with socioeconomic factors. METHODS: A descriptive study was conducted through a self administered questionnaire distributed by a software tool in social networks and non-governmental organizations from June-2014 to January-2015. Participants consisted of 601 people living in Spain. Pearson's chi(2) test and logistic regression models were applied with odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: In stable couples, the risk of RUAI increased in individuals with a medium income (OR: 1.79; 95%CI: 1.14-2.80) and in those who lived together (OR: 2.94; 95%CI: 1.74-4.98) and IUAI increased in individuals living with a partner (OR: 5.58; 95%IC: 3.24-9.59). When the partner was a friend, the risk of RUAI was higher among individuals with secondary education (OR: 2.20; 95%CI: 1.44 3.36) and those who were retired (OR: 3.6; 95%CI: 1.25-10.37), while living with a partner was a protective factor (OR: 0.56; 95%CI: 0.32-0.98). The risk of barebacking was greater in younger men (OR: 2.59; 95%CI: 1.27-5.28), in those with secondary education (OR: 1.51; 95%CI: 0.99-2.29) and in those living with a partner (OR: 3.64; 95%CI: 2.12-6.24). DISCUSSION: There is a need to reduce vulnerability due to socioeconomic factors that influence engagement in risk practices and to highlight the importance of barebacking, mainly in young MSM. Partner-based interventions and harm reduction strategies should be incorporated into preventive strategies. PMID- 26272446 TI - Using food intake records to estimate compliance with the Eatwell Plate dietary guidelines. AB - BACKGROUND: The UK Eatwell Plate is consumer based advice recommending the proportions of five food groups for a balanced diet: starchy foods, fruit and vegetables, dairy foods, nondairy sources of protein and foods and drinks high in fat or sugar. Many foods comprise ingredients from several food groups and consumers need to consider how these fit with the proportions of the Eatwell Plate. This involves disaggregating composite dishes into proportions of individual food components. The present study aimed to match the diets of adults in Scotland to the Eatwell Plate dietary recommendations and to describe the assumptions and methodological issues associated with estimating Eatwell Plate proportions from dietary records. METHODS: Foods from weighed intake records of 161 females and 151 males were assigned to a single Eatwell group based on the main ingredient for composite foods, and the overall Eatwell Plate proportions of each subject's diet were calculated. Food group proportions were then recalculated after disaggregating composite foods. RESULTS: The fruit and vegetables and starchy food groups consumed were significantly lower than recommended in the Eatwell Plate, whereas the proportions of the protein and foods high in fat or sugar were significantly higher. Failing to disaggregate composite foods gave an inaccurate estimate of the food group composition of the diet. CONCLUSIONS: Estimating Eatwell Plate proportions from dietary records is not straightforward, and is reliant on methodological assumptions. These need to be standardised and disseminated to ensure consistent analysis. PMID- 26272445 TI - Immunohistochemical localization of dopamine D2 receptor in the rat carotid body. AB - Dopamine modulates the chemosensitivity of arterial chemoreceptors, and dopamine D2 receptor (D2R) is expected to localize in the glomus cells and/or sensory nerve endings of the carotid body. In the present study, the localization of D2R in the rat carotid body was examined using double immunofluorescence for D2R with various cell markers. D2R immunoreactivity was mainly localized in glomus cells immunoreactive to tyrosine hydroxylase or dopamine beta-hydroxylase (DBH), but not in S100B-immunoreactive sustentacular cells. Furthermore, D2R immunoreactivity was observed in petrosal ganglion cells and nerve bundles in the carotid body, but not in the nerve endings with P2X2 immunoreactivity. In the carotid ganglion, a few punctate D2R-immunoreactive products were detected in DBH immunoreactive nerve cell bodies. These results showed that D2R was mainly distributed in glomus cells, and suggested that D2R plays a role in the inhibitory modulation of chemosensory activity in a paracrine and/or autocrine manner. PMID- 26272448 TI - Chlamydia Outer Protein (Cop) B from Chlamydia pneumoniae possesses characteristic features of a type III secretion (T3S) translocator protein. AB - BACKGROUND: Chlamydia spp. are believed to use a conserved virulence factor called type III secretion (T3S) to facilitate the delivery of effector proteins from the bacterial pathogen to the host cell. Important early effector proteins of the type III secretion system (T3SS) are a class of proteins called the translocators. The translocator proteins insert into the host cell membrane to form a pore, allowing the injectisome to dock onto the host cell to facilitate translocation of effectors. CopB is a predicted hydrophobic translocator protein within the chlamydial T3SS. RESULTS: In this study, we identified a novel interaction between the hydrophobic translocator, CopB, and the putative filament protein, CdsF. Furthermore, we identified a conserved PxLxxP motif in CopB (amino acid residues 166-171), which is required for interaction with its cognate chaperone, LcrH_1. Using a synthetic peptide derived from the chaperone binding motif of CopB, we were able to block the LcrH_1 interaction with either CopB or CopD; this CopB peptide was capable of inhibiting C. pneumoniae infection of HeLa cells at micromolar concentrations. An antibody raised against the N-terminus of CopB was able to inhibit C. pneumoniae infection of HeLa cells. CONCLUSION: The inhibition of the LcrH_1:CopB interaction with a cognate peptide and subsequent inhibition of host cell infection provides strong evidence that T3S is an essential virulence factor for chlamydial infection and pathogenesis. Together, these results support that CopB plays the role of a hydrophobic translocator. PMID- 26272444 TI - Impact of cataract surgery on vision-related life performances: the usefulness of Real-Life Vision Test for cataract surgery outcomes evaluation. AB - PURPOSE: Real-Life Vision Test (RLVT) is a newly developed performance-based measures of functional vision. This present study is designed to determine whether it could be a meaningful assessment for cataract surgery outcomes evaluation. PATIENTS AND METHODS: Age-related cataract patients (56) who scheduled for bilateral cataract surgery and 44 age-matched controls were evaluated by four types of measurements: (1) demographic, medical, cognitive and depressive evaluation, and the reaction time testing; (2) clinical measures (visual acuity, contrast sensitivity, stereopsis, and color perception); (3) the 25-item National Eye Institute's Visual Functioning Questionnaire (NEI-VFQ); (4) the RLVT. Spearman's coefficients and multiple regression analysis were conducted to investigate the relationship among RLVT, clinical measures, and self-report assessment of visual function. RESULTS: The results of RLVT, clinical measures, and NEI-VFQ total scores were improved significantly after cataract surgery. There were no differences between control subjects and post-surgery patients with respect to NEI-VFQ-25 total scores, self-rating depression scale scores and three tasks of RLVT. Change of RLVT was significantly associated with the change of clinical measures in the cataract group. Multiple regression analysis demonstrated that change of distance, intermediate, and near visual acuity, and binocular contrast sensitivity were significant predictors of improvements of RLVT. CONCLUSIONS: Cataract surgery could improve real-world visual ability effectively for cataract patients. Our study highlights the potential usefulness of RLVT as an adjunct to the current outcomes evaluation system for cataract surgery. The use of RLVT combined with clinical and self-survey methods may be the comprehensive strategy to manifest the impact of cataract surgery on patients' overall vision-related quality of life. PMID- 26272449 TI - A case study for evaluating potential soil sensitivity in aridland systems. AB - Globally, ecosystems are subjected to prolonged droughts and extreme heat events, leading to forest die-offs and dominance shifts in vegetation. Some scientists and managers view soil as the main resource to be considered in monitoring ecosystem responses to aridification. As the medium through which precipitation is received, stored, and redistributed for plant use, soil is an important factor in the sensitivity of ecosystems to a drying climate. This study presents a novel approach to evaluating where on a landscape soils may be most sensitive to drying, making them less resilient to disturbance, and where potential future vegetation changes could lead to such disturbance. The drying and devegetation of arid lands can increase wind erosion, contributing to aerosol and dust emissions. This has implications for air quality, human health, and water resources. This approach combines soil data with vegetation simulations, projecting future vegetation change, to create maps of potential areas of concern for soil sensitivity and dust production in a drying climate. Consistent with recent observations, the projections show shifts from grasslands and woodlands to shrublands in much of the southwestern region. An increase in forested area occurs, but shifts in the dominant types and spatial distribution of the forests also are seen. A net increase in desert ecosystems in the region and some changes in alpine and tundra ecosystems are seen. Approximately 124,000 km(2) of soils flagged as "sensitive" are projected to have vegetation change between 2041 and 2050, and 82,927 km(2) of soils may become sensitive because of future vegetation changes. These maps give managers a way to visualize and identify where soils and vegetation should be investigated and monitored for degradation in a drying climate, so restoration and mitigation strategies can be focused in these areas. PMID- 26272447 TI - Comparison of the Effect of Massage Therapy and Isometric Exercises on Primary Dysmenorrhea: A Randomized Controlled Clinical Trial. AB - STUDY OBJECTIVE: Dysmenorrhea is the most common cyclic pelvic pain, and it affects the quality of life of many women. We sought to compare the effects of massage and isometric exercises on primary dysmenorrhea. DESIGN, SETTING, AND PARTICIPANTS: We conducted a randomized controlled trial at the dormitories of Shiraz University among 102 students with primary dysmenorrheal. INTERVENTIONS: The student groups were randomly divided into massage, isometric exercises, and control groups. The first group received 2 consecutive cycles of effleurage massage with lavender oil. The second group had 8 weeks of isometric exercises. No intervention was performed for the control group. MAIN OUTCOME MEASUREMENTS: Pain intensity was measured and recorded by using a visual analog scale. In addition, the duration of pain was measured in hours, and Spielberger's questionnaire was used to measure the anxiety level. RESULTS: Pain intensity had significantly reduced in the massage and exercises groups; the reduction was more significant in the massage group (P < .001). The results revealed a significant difference among the 3 groups in regard to the mean duration of pain after the third cycle (P = .006). However, no significant difference was found among the 3 groups concerning the mean level of anxiety. The results of intragroup comparisons only showed a significant reduction of anxiety level in the massage group after the third cycle (P = .017). CONCLUSION: Based on the present findings, it seems that massage therapy and isometric exercises were effective in reducing some symptoms of dysmenorrhea. PMID- 26272450 TI - Absolute bioavailability and pharmacokinetics of the angiotensin II receptor antagonist fimasartan in healthy subjects. AB - The present study was conducted to determine the absolute bioavailability of fimasartan (FMS; Kanarb((r)) ) after the single oral administration of a 60-mg tablet or a single 30-mg intravenous (IV) infusion. This investigation was a randomized, single-dose, open-labeled, two-way crossover study of 16 healthy Korean male subjects. The subjects were divided into two groups (n = 8) and each received either the oral or IV formulation followed by one-week washout period. The Cmax (ng/ml) and AUCinfinity (h . ng/ml) following oral and IV administration were 62.4 +/- 48.6 and 291.1 +/- 121.7; and 683.3 +/- 104.3 and 782.3 +/- 112.7 (mean +/- SD), respectively. The Tmax (h) were 3.0 h (range: 0.5-5.0 h) and 1.0 h (range: 0.8-1.0 h) in the test and reference groups, respectively. The terminal elimination half-lives (t1/2 , h) were similar (5.8 and 5.5 h, respectively) indicating that the route of administration did not influence the absorption or elimination of FMS. The systemic clearance (CL, L/h) and the volume of distribution at steady-state (Vdss , L) were 331.3 +/- 444.5 L/h and 403.3 +/- 710.4 L following oral administration and 39.1 +/- 5.3 L/h and 42.4 +/- 25.5 L following IV administration. The absolute bioavailability of the FMS tablet was 18.6%. PMID- 26272451 TI - Knowledge and attitudes regarding medical research studies among patients with breast cancer and gynecological diseases. AB - BACKGROUND: Medical research studies are becoming increasingly important for optimizing the prevention, diagnosis and treatment of illnesses. Participation in research studies can have many benefits for patients. In randomized and controlled clinical studies, they can receive the best possible medical care currently available. However, only a small proportion of patients nowadays are treated within the framework of medical research. The primary endpoint of this study was to discover what level of knowledge patients have about clinical studies and how they currently perceive them, in order to identify ways of optimizing the information provided about studies from the patients' point of view. METHODS: The study included 2546 patients (breast cancer 21.6%, gynecological cancer 8.3%, obstetrics 32.7%, endometriosis 7.8%, fertility treatment 3.2%, other benign gynecological illnesses 19.2%, no information for 7.2%) in the outpatient clinic (45.2%) and in the in-patient sector (54.8%) at the Department of Gynecology at Erlangen University Hospital and associated centers. In the single-center study, conducted between January 2011 and January 2012, the patients were asked about their level of knowledge regarding the background to medical research studies and the ways in which they are carried out and used. The patients were also asked how they perceived medical studies and how they thought study conditions might be optimized. The three-page questionnaire was included in the feedback sheet received by patients as part of the hospital's quality management system. RESULTS: As a whole, the group only had moderate knowledge about clinical studies. A majority of the respondents considered that studies were valuable (91.6%), but only a few were also willing to take part in them (58.4%). Knowledge and willingness to participate strongly depended on age (P < 0.001), educational level (P < 0.001) and patient group (P < 0.001). Most patients would prefer to decide about participating in studies through a discussion with their outpatient physicians. CONCLUSIONS: The information that patients have about clinical studies affects whether they participate in them. It is therefore extremely important for patients to be well informed, for their anxieties about participation to be relieved, and for the benefits of participation to be explained to them. PMID- 26272453 TI - Inter-rater Reliability of Criteria-Based Content Analysis of Children's Statements of Abuse. AB - The evaluation of children's statements of sexual abuse cases in forensic cases is critically important and must and reliable. Criteria-based content analysis (CBCA) is the main component of the statement validity assessment (SVA), which is the most frequently used approach in this setting. This study investigated the inter-rater reliability (IRR) of CBCA in a forensic context. Three independent raters evaluated the transcripts of 95 statements of sexual abuse. IRR was calculated for each criterion, total score, and overall evaluation. The IRR was variable for the criteria, with several being unsatisfactory. But high IRR was found for the total CBCA scores (Kendall's W=0.84) and for overall evaluation (Kendall's W=0.65). Despite some shortcomings, SVA remains a robust method to be used in the comprehensive evaluation of children's statements of sexual abuse in the forensic setting. However, the low IRR of some CBCA criteria could justify some technical improvements. PMID- 26272454 TI - Long-term three-dimensional volumetric assessment of skin tightening using a sharply tapered non-insulated microneedle radiofrequency applicator with novel fractionated pulse mode in asians. AB - BACKGROUND AND OBJECTIVE: Non-insulated microneedle radiofrequency (NIMNRF) is a novel method that allows non-thermal penetration of the epidermis followed by radiofrequency (RF) coagulation at selected depths of the dermis that are surrounded by a zone of non-coagulative volumetric heating. The objective of this study was to investigate subjectively and objectively the efficacy of a single fractional NIMNRF treatment. STUDY DESIGN/MATERIALS AND METHODS: Twenty Japanese patients underwent full face skin tightening using a sharply tapered NIMNRF applicator with a novel fractionated pulse mode. The system platform (1MHZ) incorporated six independent phase controlled RF generators coupled to RF microneedles that induced skin remodeling via controlled dermal coagulation. Patients received from 500 to 1000 pulses that were 80-110 milliseconds in duration at a power of 10-14 W, and a 1.5-2.5 mm penetration depth. Topical anesthetic cream was applied before the treatment. Monthly three-dimensional (3 D) volumetric assessments were performed for 6 months after treatment. Patients rated their satisfaction using a 5-point scale. RESULTS: During the study patients showed significant skin tightening on the lower two-thirds of the face. Objective assessments with superimposed 3-D color images showed significant median volumetric reduction of 12.1 ml at 6 months post-treatment. Ninety percent of the patients were either "satisfied" or "very satisfied" with the treatment results. The treatments were well tolerated with minimal discomfort. Complications included a slight burning sensation and mild erythema that were minor and transitory; both resolved within 5 hours. Side effects such as post inflammatory hyperpigmentation, epidermal burns, and scar formation were not observed. CONCLUSION: The advantages of this NIMNRF treatment for skin tightening are its long-lasting high efficacy as shown through 3-D volumetric assessments. Moreover, NIMNRF produced minimal complications and downtime as well as few side effects. This non-invasive novel fractional NIMNRF approach provides safe and effective treatment of skin tightening in Asian patients. PMID- 26272452 TI - Continuous wound infusion of local anesthetic and steroid after major abdominal surgery: study protocol for a randomized controlled trial. AB - BACKGROUND: Inflammatory response is one of the key components of pain perception. Continuous infusion (CWI) of local anesthetics has been shown to be effective in controlling pain and reducing postoperative morphine consumption, but the effect of adding a potent anti-inflammatory drug (such as a steroid) has never been addressed. In our study, we want to investigate the effect of CWI with local anesthetic + methylprednisolone on acute and persistent pain, correlating clinical data with biomarkers of inflammation and genetic background. METHODS/DESIGN: After approval by their institutional review board, three hospitals will enroll 120 patients undergoing major abdominal surgery in a randomized, double-blind, phase III study. After a 24-h CWI of ropivacaine 0.2 % + methylprednisolone 1 mg/kg, patients will be randomly assigned to receive either ropivacaine + steroid or placebo for the next 24 h. Then, patient controlled CWI with only ropivacaine 0.2 % or placebo (according to the group of randomization) is planned after 48 h up to 7 days (bolus 10 ml, lock-out 1 h, maximum dose of 40 ml in 4 h). Morphine equivalent consumption up to 7 days will be analyzed, together with any catheter- or drug-related side effect. Persistent post-surgical pain (PPSP) incidence will also be investigated. Our primary endpoint is analgesic consumption in the first 7 days after surgery; we will evaluate, as secondary endpoints, any catheter- or drug-related side effect, genotype/phenotype correlations between some polymorphisms and postoperative outcome in terms of morphine consumption, development of the inflammatory response, and incidence of PPSP. Finally, we will collect, in a subgroup of patients, wound exudate samples by micro-dialysis, blood samples, and urine samples up to 72 h to investigate local and systemic inflammation and oxidative stress. DISCUSSION: This is a phase III trial to evaluate the safety and efficacy of wound infusion with steroid and local anesthetic. The study is aimed also to evaluate how long this infusion has to be maintained in order to maximize effectiveness. Our data are intended to quantify the amount of ropivacaine and methylprednisolone needed by patients undergoing major abdominal surgery, to be stored in a new nanotechnology device for sustained pain treatment after surgery. We also aim to clarify the roles of inflammatory response, oxidative stress, and genetic background on postoperative and persistent pain after major abdominal surgery. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov ( NCT02002663 ) on 24 Oct. 2013. PMID- 26272455 TI - Outcome and prognostic factors of multimodal therapy for pulmonary large-cell neuroendocrine carcinomas. AB - BACKGROUND: There is controversy whether patients diagnosed with large-cell neuroendocrine carcinoma (LCNEC) should be treated according to protocols for non small cell lung cancers (NSCLC) or small cell lung cancers (SCLC), especially with regard to the administration of prophylactic cranial irradiation (PCI). This study was set up to determine the incidence of brain metastases and to investigate the outcome following multimodal treatment in 70 patients with LCNEC. METHODS: Seventy patients with histologically confirmed LCNEC were treated at the University Hospital of Heidelberg between 2001 and 2014. Data were collected retrospectively. Al most all patients received thoracic surgery as initial treatment (94 %). Chemotherapy was administered in 32 patients as part of the initial treatment. Fourteen patients were treated with adjuvant or definitive thoracic radiotherapy according to NSCLC protocols. Cranial radiotherapy due to brain metastases, mostly given as whole brain radiotherapy (WBRT), was received by fourteen patients. Statistical analysis was performed using the long-rank test and the Kaplan-Meier method. RESULTS: Without PCI, the detected rate for brain metastases was 25 % after a median follow-up time of 23.4 months, which is comparable to NSCLC patients in general. Overall (OS), local (LPFS), brain metastases-free survival (BMFS) and extracranial distant progression-free survival (eDPFS) was 43, 50, 63 and 50 % at 5 years, respectively. Patients with incomplete resection showed a survival benefit from adjuvant radiotherapy. The administration of adjuvant chemotherapy improved the general worse prognosis in higher pathologic stages. CONCLUSION: In LCNEC patients, the administration of radiotherapy according to NSCLC guidelines appears reasonable and contributes to acceptable results of multimodal treatment regimes. The low incidence of spontaneous brain metastases questions a possible role of PCI. PMID- 26272458 TI - The time scale of the quaternary structural changes in hemoglobin revealed using the transient grating technique. AB - The quaternary structural transition between the R and T states of human hemoglobin was investigated using the transient grating technique. The results presented herein reveal that the quaternary structural change accompanied by the R-T transition occurs within a few microseconds. PMID- 26272457 TI - Analysis of NSCLC tumour heterogeneity, proliferative and 18F-FDG PET indices reveals Ki67 prognostic role in adenocarcinomas. AB - AIMS: The role of tumour metabolic and proliferative indices in predicting non small-cell lung cancer (NSCLC) patients' prognosis is unclear. We correlated fluorine 18 ((18) F)-fluorodeoxyglucose (FDG)-positron emission tomography (PET) value and Ki67 index to patients' survival, taking into account tumour heterogeneity, disease characteristics and genetic aberrations. METHODS AND RESULTS: A series of 383 NSCLCs was arranged into tissue microarrays and Ki67 staining was analysed by immunohistochemistry. The maximum standardized uptake (SUV(MAX) ) value detected by (18) F-FDG-PET analysis was calculated over a region of interest. Large-cell and squamous cell carcinomas had higher proliferative and metabolic activities than adenocarcinomas, and the two measures were correlated significantly. The hot-spot Ki67 value was correlated with patients' survival and the cut-off to discriminate patients in the survival risk groups was 20%. Ki67 hot-spot values were greater in anaplastic lymphoma kinase (ALK) rearranged tumours. Adenocarcinomas showed the highest intratumour heterogeneity in proliferative activity and the hot-spot Ki67 value predicted only the prognosis of patients in this group. Although tumour metabolic activity was not associated with patients' prognosis, a SUV(MAX) > 2 was related to nodal metastases, tumour size and grade. CONCLUSIONS: Our results highlight how tumour heterogeneity influences evaluation of prognostic biomarkers. Our data support Ki67 evaluation to estimate NSCLC patients' prognosis, particularly for adenocarcinoma. PMID- 26272456 TI - Individual identification via electrocardiogram analysis. AB - BACKGROUND: During last decade the use of ECG recordings in biometric recognition studies has increased. ECG characteristics made it suitable for subject identification: it is unique, present in all living individuals, and hard to forge. However, in spite of the great number of approaches found in literature, no agreement exists on the most appropriate methodology. This study aimed at providing a survey of the techniques used so far in ECG-based human identification. Specifically, a pattern recognition perspective is here proposed providing a unifying framework to appreciate previous studies and, hopefully, guide future research. METHODS: We searched for papers on the subject from the earliest available date using relevant electronic databases (Medline, IEEEXplore, Scopus, and Web of Knowledge). The following terms were used in different combinations: electrocardiogram, ECG, human identification, biometric, authentication and individual variability. The electronic sources were last searched on 1st March 2015. In our selection we included published research on peer-reviewed journals, books chapters and conferences proceedings. The search was performed for English language documents. RESULTS: 100 pertinent papers were found. Number of subjects involved in the journal studies ranges from 10 to 502, age from 16 to 86, male and female subjects are generally present. Number of analysed leads varies as well as the recording conditions. Identification performance differs widely as well as verification rate. Many studies refer to publicly available databases (Physionet ECG databases repository) while others rely on proprietary recordings making difficult them to compare. As a measure of overall accuracy we computed a weighted average of the identification rate and equal error rate in authentication scenarios. Identification rate resulted equal to 94.95 % while the equal error rate equal to 0.92 %. CONCLUSIONS: Biometric recognition is a mature field of research. Nevertheless, the use of physiological signals features, such as the ECG traits, needs further improvements. ECG features have the potential to be used in daily activities such as access control and patient handling as well as in wearable electronics applications. However, some barriers still limit its growth. Further analysis should be addressed on the use of single lead recordings and the study of features which are not dependent on the recording sites (e.g. fingers, hand palms). Moreover, it is expected that new techniques will be developed using fiducials and non-fiducial based features in order to catch the best of both approaches. ECG recognition in pathological subjects is also worth of additional investigations. PMID- 26272459 TI - Meta-analysis shows that obesity may be a significant risk factor for prosthetic joint infections. AB - PURPOSE: Our aim was to evaluate the association between the different degree of obesity and prosthetic joint infections (PJIs) after total hip replacement (THR) by performing a meta-analysis. METHODS: PubMed, Cochrane library and Embase databases up to May, 2014 were retrieved for identifying relevant studies. Relative risk (RR) and their 95 % confidence intervals (CIs) were used as effect sizes. RESULTS: A total of 15 articles were included in this meta-analysis. The overall analyses showed that the risk of PJIs in the BMI >= 30 group and in BMI >= 40 group were significantly higher than that in the BMI < 30 group. As well, the prospective pooled results showed that overweight and obesity could significantly increase the incidence of PJIs. CONCLUSIONS: Our meta-analysis indicates that all of obesity levels can significantly increase the risk of PJIs. However, further studies with more strict design are need in the future. PMID- 26272460 TI - Comparison of perpendicular to the coronal plane versus medial inclination for atlas pedicle screw insertion: an anatomic and radiological study in human cadavers. AB - PURPOSE: To ascertain the anatomic and radiological parameters of the atlas (C1) pedicle and to explore a preferable method of C1 pedicle screw insertion. METHODS: Thirty-four conserved human cadaveric cervical spines (20 males, 14 females) underwent computed tomography (CT) scanning. Trajectories P (perpendicular to the coronal plane) and I (with medial inclination) were designed for each C1 pedicle on CT images. External pedicle wall width, medullary cavity width, transverse angle, and optimal entry point along each trajectory were measured. Cortical screws of 3.5 mm in diameter were inserted into C1 pedicles along trajectory P and I, respectively, and wall perforation was assessed (post-operative CT scanning). RESULTS: The external pedicle wall width and medullary cavity width along trajectory I were significantly wider than trajectory P (P < 0.01). Although external pedicle wall widths were all greater than 3.5 mm, medullary cavity width <3.5 mm was found in 16.1 % pedicles along trajectory P and only 2.9 % along trajectory I. Transverse angle was 21.8 degrees along trajectory I and 0 degrees along trajectory P. Optimal entry point of trajectory I was 4.1 mm lateral from that of trajectory P. The lateral wall perforation rate was significantly lower along trajectory I than trajectory P (P < 0.05). CONCLUSIONS: C1 pedicle screw trajectory with medial inclination and more lateral entry points yielded wider medullary cavity width than that perpendicular to the coronal plane, and might minimize lateral wall perforation. PMID- 26272461 TI - Relationship between Vasectomy and Sexual Frequency. AB - INTRODUCTION: Men who are considering vasectomy as a means of contraception may have significant anxiety about their future sexual potency. As a result, couples may choose other forms of contraception with lower efficacy. AIM: We sought to determine the relationship between vasectomy and the frequency of sexual intercourse. METHODS: We analyzed data from cycles 6 (2002) to 7 (2006-2008) of the National Survey of Family Growth to compare the frequency of sexual intercourse of men who had undergone vasectomy with men who had not. Analysis was performed using data from male and female responders, and excluded men who had never had sex and those below age 25. We constructed a multivariate logistic regression model to adjust for demographic, socioeconomic, reproductive, and health factors. MAIN OUTCOME MEASURE: The main outcome measure was the sexual frequency in the last 4 weeks. RESULTS: Among male responders, a total of 5838 men met criteria for our study; 353 had undergone vasectomy. For vasectomized men, the average frequency of sexual intercourse was 5.9 times per month compared with 4.9 times for nonvasectomized men. After adjusting for age, marital status, race, education, health, body mass index, children, and income, vasectomized men had an 81% higher odds (95% confidence interval [CI] 6-201%) of having intercourse at least once a week compared with nonvasectomized men. A total number of 5211 female respondents reported 670 of their partners had undergone vasectomy. For partners of vasectomized men, the average frequency of intercourse was 6.3 times per month, compared with 6.0 times for partners of nonvasectomized men. After adjustment, women with vasectomized partners had a 46% higher odds (95% CI 5-103%) of having sexual intercourse at least once a week compared with women with nonvasectomized partners (P = 0.024). CONCLUSION: Vasectomy is not associated with decreased sexual frequency. This finding may be helpful to couples as they consider contraceptive options. PMID- 26272463 TI - Morphology and ontogeny of multiple lateral-line canals in the rock prickleback, Xiphister mucosus (Cottiformes: Zoarcoidei: Stichaeidae). AB - The structure and ontogeny of lateral-line canals in the Rock Prickleback, Xiphister mucosus, were studied using cleared-and-stained specimens, and the distribution and morphology of neuromasts within lateral-line canals were examined using histology. X. mucosus has seven cephalic canals in a pattern that, aside from four branches of the infraorbital canals, is similar to that of most teleostean fishes. Unlike most other teleosts, however, X. mucosus features multiple trunk lateral-line canals. These include a short median posterior extension of the supratemporal canal and three paired, branching canals located on the dorsolateral, mediolateral, and ventrolateral surfaces. The ventrolateral canal (VLC) includes a loop across the ventral surface of the abdomen. All trunk canals, as well as the branches of the infraorbitals, are supported by small, dermal, ring-like ossifications that develop independently from scales. Trunk canals develop asynchronously with the mediodorsal and dorsolateral canals (DLC) developing earliest, followed by the VLC, and, finally, by the mediolateral canal (MLC). Only the mediodorsal and DLC connect to the cephalic sensory canals. Fractal analysis shows that the complexity of the trunk lateral-line canals stabilizes when all trunk canals develop and begin to branch. Histological sections show that neuromasts are present in all cephalic canals and in the DLC and MLC of the trunk. However, no neuromasts were identified in the VLC or its abdominal loop. The VLC cannot, therefore, directly function as a part of the mechanosensory system in X. mucosus. The evolution and functional role of multiple lateral-line canals are discussed. PMID- 26272462 TI - Overproduction of pro-transglutaminase from Streptomyces hygroscopicus in Yarrowia lipolytica and its biochemical characterization. AB - BACKGROUND: Transglutaminases (TGase), synthesized as a zymogen (pro-TGase) in Streptomyces sp., are important enzymes in food industry. Due to the important applications of TGase in food industry, obtaining robust and food-safe TGase producing strains has attracted much attention during the past decade. In this study, Streptomyces hygroscopicus pro-TGase was efficiently expressed and secreted by a food-grade host, Yarrowia lipolytica, without antibiotic markers. RESULTS: The pro-TGase gene was cloned into integrative vectors pINA1296 (monocopy) and pINA1297 (multicopy), and was used to transform the Y. lipolytica Po1g or Po1h strain, respectively. Expression was driven by a recombinant hp4d promoter and secretion obtained using a XPR2 pre-sequence as a signal peptide. The highest yield of extracellular pro-TGase produced by the recombinant Po1h strain corresponded to 5.3 U/mL of TGase, a level 8.8 fold higher than that obtained using the recombinant Po1g strain. Asparagines in two potential Asn linked glycosylation sites (Asn160 and Asn355) from pro-TGase were mutated to glutamine individually or simultaneously, yielding the deglycosylated variants N160Q, N355Q, and N160Q/N355Q. The activities of N160Q, N355Q and N160Q/N355Q constructs were respectively 5.3 U/mL, 7.8 U/mL, and 3.0 U/mL, equivalent to 100 %, 147 %, and 57 % of that from wild-type pro-TGase. The TGase yield of N355Q variant was raised to 35.3 U/mL of by using a glycerol feeding strategy in a 3 L fermenter. The optimal pH and temperature of the activated pro-TGase, and of its deglycosylated variants, were in the range of 5.0-6.0 pH and 40-45 degrees C, respectively. The half-life of the recombinant wild-type pro-TGase at 37 degrees C reached 34.0 min, and those of the variants were from 24.2 min to 11.5 min. In contrast to the wild-type pro-TGase, all of the variants had decreased specific activities, and both the K m and k cat values of the variants decreased accordingly. CONCLUSIONS: This study constitutes the first report of the heterologous expression of a pro-TGase in Y. lipolytica, and provides new possibilities for the efficient production of TGases used in food processing. PMID- 26272464 TI - Primary pulmonary angiosarcoma: A case report. AB - Primary sarcoma is uncommon in the lung, and primary angiosarcoma is exceedingly rare. We report a case of primary pulmonary angiosarcoma of the left lung with emphasis on its growth pattern in the lung. A 48-year-old Japanese man was admitted to our hospital because of dyspnea on exertion. He was subsequently found to have left pleural effusion. Computed tomography shows a nodular lesion measuring 7 * 4 cm in his left lung. Obstruction of the left inferior lobar bronchus was observed, and endobronchial biopsy suggested angiosarcoma. Left pneumonectomy was performed. On macroscopic examination of the cut surface, multiple nodular lesions were observed particularly in portions around branches of pulmonary artery along bronchioles. Histological examination revealed vascular channel-like structure with vague lumen formations by atypical polygonal or spindle-shaped neoplastic cells. Immunohistochemically, the neoplastic cells are positive for FLI-1, ERG, CD31 and von Willebrand factor/factor VIII-related antigen, but not CD34. Angiosarcoma is a particularly rare form of primary pulmonary tumors, and this case report describes its unique macroscopic growth pattern in the lung. PMID- 26272465 TI - Design and synthesis of a berberine dimer: a fluorescent ligand with high affinity towards G-quadruplexes. AB - G-quadruplexes (G4) are thought to be important factors for telomerase inhibition and transcriptional/translational modulations. Bioinformatic analyses imply that the human genome and mRNA contain a multitude of G4-forming sequences; however, their analysis requires selective and detectable ligands. Given that two molecules of fluorescent berberine (BBR) coordinate to telomeric G4 in their co crystals, we designed hydrocarbon-linked BBR-analogue dimers because we expected the alignment of two BBR chromophores would avoid Watson-Crick base pair intercalation, which should result in high selectivity towards G4. An alkene-cis C2 BBR dimer showed the highest affinity (Kd <=2.6 nM) and selectivity (ca. 900 fold vs. duplex) towards G4. The intrinsic "light-up" fluorescence properties of this BBR dimer, derived from its conformational switching by G4, allowed a selective visualization of various G4 in the gel without using additional bulky fluorescence dyes, which, combined with the observed lack of conformational change of the ligand, suggested future applications in in vitro detection systems. PMID- 26272466 TI - Depressive Symptoms and Momentary Mood Predict Momentary Pain Among Rheumatoid Arthritis Patients. AB - BACKGROUND: Although a relationship between mood and pain has been established cross-sectionally, little research has examined this relationship using momentary within-person data. PURPOSE: We examined whether baseline depressive symptoms and within-person levels of negative and positive mood predicted momentary pain among 31 individuals with rheumatoid arthritis (RA). METHODS: Depressive symptomatology was measured at baseline. Mood and RA symptoms were self-reported via ecological momentary assessment five times a day for seven consecutive days. Analyses controlled for gender, age, weekend day, time of day, and experiences of stress. RESULTS: Greater momentary positive mood was associated with less momentary pain and fewer arthritis-related restrictions; negative mood was associated with more restrictions. Greater depressive symptomatology also predicted more pain and restrictions, an effect which was not accounted for by mood. CONCLUSIONS: Results suggest that both depression and mood are uniquely associated with momentary pain; as such, multi-component interventions may provide optimal disease management. PMID- 26272467 TI - Merino and Merino-derived sheep breeds: a genome-wide intercontinental study. AB - BACKGROUND: Merino and Merino-derived sheep breeds have been widely distributed across the world, both as purebred and admixed populations. They represent an economically and historically important genetic resource which over time has been used as the basis for the development of new breeds. In order to examine the genetic influence of Merino in the context of a global collection of domestic sheep breeds, we analyzed genotype data that were obtained with the OvineSNP50 BeadChip (Illumina) for 671 individuals from 37 populations, including a subset of breeds from the Sheep HapMap dataset. RESULTS: Based on a multi-dimensional scaling analysis, we highlighted four main clusters in this dataset, which corresponded to wild sheep, mouflon, primitive North European breeds and modern sheep (including Merino), respectively. The neighbor-network analysis further differentiated North-European and Mediterranean domestic breeds, with subclusters of Merino and Merino-derived breeds, other Spanish breeds and other Italian breeds. Model-based clustering, migration analysis and haplotype sharing indicated that genetic exchange occurred between archaic populations and also that a more recent Merino-mediated gene flow to several Merino-derived populations around the world took place. The close relationship between Spanish Merino and other Spanish breeds was consistent with an Iberian origin for the Merino breed, with possible earlier contributions from other Mediterranean stocks. The Merino populations from Australia, New Zealand and China were clearly separated from their European ancestors. We observed a genetic substructuring in the Spanish Merino population, which reflects recent herd management practices. CONCLUSIONS: Our data suggest that intensive gene flow, founder effects and geographic isolation are the main factors that determined the genetic makeup of current Merino and Merino-derived breeds. To explain how the current Merino and Merino-derived breeds were obtained, we propose a scenario that includes several consecutive migrations of sheep populations that may serve as working hypotheses for subsequent studies. PMID- 26272469 TI - Anomalous Anisotropic Thermal Expansion in a One-Dimensional Coordination Polymer Driven by Conformational Flexibility. AB - A one-dimensional lithium(I) coordination polymer has been characterized by variable-temperature single-crystal X-ray diffraction and differential scanning calorimetry. This compound possesses an anisotropic packing arrangement that, along with a scissor-like or hingelike movement of the pyridyl ligand side arms, results in an extremely rare combination of positive, negative, and zero thermal expansion. Designing such types of materials and understanding the mechanistic details can facilitate the design of new thermoresponsive materials. PMID- 26272468 TI - Adjuvant treatment with dexamethasone plus anti-C5 antibodies improves outcome of experimental pneumococcal meningitis: a randomized controlled trial. AB - BACKGROUND: We compared adjunctive treatment with placebo, dexamethasone, anti-C5 antibodies, and the combination of dexamethasone plus anti-C5 antibodies in experimental pneumococcal meningitis. METHODS: In this prospective, investigator blinded, randomized trial, 96 mice were infected intracisternally with 10(7) CFU/ml Streptococcus pneumoniae serotype 3, treated with intraperitoneal ceftriaxone at 20 h, and randomly assigned to intraperitoneal adjunctive treatment with placebo (saline), dexamethasone, anti-C5 antibodies, or dexamethasone plus anti-C5 antibodies. The primary outcome was survival during a 72-h observational period that was analyzed with the log-rank test. Secondary outcome was clinical severity, scored on a validated scale using a linear mixed model. RESULTS: Mortality rates were 16 of 16 mice (100%) in the placebo group, 12 of 15 mice (80%) in the dexamethasone group, 25 of 31 mice (80%) in the anti C5 antibody group, and 18 of 30 mice (60%) in the dexamethasone plus anti-C5 antibody group (Fisher's exact test for overall difference, P = .012). Mortality of mice treated with dexamethasone plus anti-C5 antibodies was lower compared to the anti-C5 antibody-treated mice (log-rank P = .039) and dexamethasone-treated mice (log-rank P = .040). Clinical severity scores for the dexamethasone plus anti-C5 antibody-treated mice increased more slowly (0.199 points/h) as compared to the anti-C5 antibody-treated mice (0.243 points/h, P = .009) and dexamethasone treated mice (0.249 points/h, P = .012). Modeling of severity data suggested an additive effect of dexamethasone and anti-C5 antibodies. CONCLUSION: Adjunctive treatment with dexamethasone plus anti-C5 antibodies improves survival in severe experimental meningitis caused by S. pneumoniae serotype 3, posing an important new treatment strategy for patients with pneumococcal meningitis. PMID- 26272470 TI - Prioritizing Zoonotic Diseases: Differences in Perspectives Between Human and Animal Health Professionals in North America. AB - Zoonoses pose a significant burden of illness in North America. Zoonoses represent an additional threat to public health because the natural reservoirs are often animals, particularly wildlife, thus eluding control efforts such as quarantine, vaccination and social distancing. As there are limited resources available, it is necessary to prioritize diseases in order to allocate resources to those posing the greatest public health threat. Many studies have attempted to prioritize zoonoses, but challenges exist. This study uses a quantitative approach, conjoint analysis (CA), to overcome some limitations of traditional disease prioritization exercises. We used CA to conduct a zoonoses prioritization study involving a range of human and animal health professionals across North America; these included epidemiologists, public health practitioners, research scientists, physicians, veterinarians, laboratory technicians and nurses. A total of 699 human health professionals (HHP) and 585 animal health professionals (AHP) participated in this study. We used CA to prioritize 62 zoonotic diseases using 21 criteria. Our findings suggest CA can be used to produce reasonable criteria scores for disease prioritization. The fitted models were satisfactory for both groups with a slightly better fit for AHP compared to HHP (84.4% certainty fit versus 83.6%). Human-related criteria were more influential for HHP in their decision to prioritize zoonoses, while animal-related criteria were more influential for AHP resulting in different disease priority lists. While the differences were not statistically significant, a difference of one or two ranks could be considered important for some individuals. A potential solution to address the varying opinions is discussed. The scientific framework for disease prioritization presented can be revised on a regular basis by updating disease criteria to reflect diseases as they evolve over time; such a framework is of value allowing diseases of highest impact to be identified routinely for resource allocation. PMID- 26272471 TI - Hybrid treatment of atrial fibrillation. AB - Endocardial catheter ablation (CA) and surgical Maze-like procedures have become mainstays of interventional treatment for atrial fibrillation (AF). However, CA has limited efficacy particularly in patients with persistent AF who have a high risk of recurrent AF. Epicardial CA in conjunction with endocardial CA, a hybrid CA, offers the potential advantage for robust lesion formation, left atrial debulking, and mapping and CA of residual arrhythmia circuits. Hybrid CA procedures may improve the success rate of an ablation procedure for AF, particularly in those with persistent or long-standing persistent AF and those with significant structural heart disease. However, the ideal patient populations who may benefit from hybrid AF ablation and the ideal tools and techniques for hybrid AF ablation have yet to be determined. In this review, we discuss the hybrid CA procedure including motivation for and methods of hybrid CA, available tools, and reported efficacy of the procedure. PMID- 26272472 TI - Mechanistic insight into the dramatic improvement of probucol dissolution in neutral solutions by solid dispersion in Eudragit E PO with saccharin. AB - OBJECTIVES: Solid dispersion using Eudragit E PO (EPO) improves the dissolution of poorly water-soluble drugs in acidic solutions; however, the dissolution extremely decreases in neutral solutions. In this report, ternary solid dispersions containing probucol (PBC), EPO, and saccharin (SAC) were prepared to enable high drug dissolution at neutral pH. METHODS: Cryogenic-grinding was used to obtain ternary solid dispersions. Dissolution tests at neutral pH values were conducted to confirm the usefulness of the cryogenic-ground mixture (cryo-GM). The molecular state of each component and intermolecular interactions in the ternary cryo-GM were evaluated using powder X-ray diffraction (PXRD) and (13) C solid-state NMR including spin-lattice relaxation time evaluation. KEY FINDINGS: PBC dispersed in ternary cryo-GM had an improved dissolution in neutral solutions. PBC and SAC were in amorphous states in EPO polymer matrices. The weak hydrophobic interaction between PBC and EPO and the ionic bond or hydrogen bond between EPO and SAC were demonstrated. These two molecular interactions improved the dissolution of PBC in neutral solutions. CONCLUSION: Preparation of ternary solid dispersion is a potential method of improving drug solubility and absorption. PMID- 26272473 TI - Health-care providers' experiences with opt-out HIV testing: a systematic review. AB - HIV is now a manageable chronic disease with a good prognosis, but early detection and referral for treatment are vital. In opt-out HIV testing, patients are informed that they will be tested unless they decline. This qualitative systematic review explored the experiences, attitudes, barriers, and facilitators of opt-out HIV testing from a health-care provider (HCP) perspective. Four articles were included in the synthesis and reported on findings from approximately 70 participants, representing diverse geographical regions and a range of human development status and HIV prevalence. Two synthesized findings emerged: HCP attitudes and systems. The first synthesized finding encompassed HCP decision-making attitudes about who and when to test for HIV. It also included the assumptions the HCPs made about patient consequences. The second synthesized finding related to systems. System-related barriers to opt-out HIV testing included lack of time, resources, and adequate training. System-related facilitators included integration into standard practice, support of the medical setting, and electronic reminders. A common attitude among HCPs was the outdated notion that HIV is a terrible disease that equates to certain death. Some HCPs stated that offering the HIV test implied that the patient had engaged in immoral behaviour, which could lead to stigma or disengagement with health services. This paternalism diminished patient autonomy, because patients who were excluded from opt-out HIV testing could have benefited from it. One study highlighted the positive aspects of opt-out HIV testing, in which participants underscored the professional satisfaction that arose from making an HIV diagnosis, particularly when marginalized patients could be connected to treatment and social services. Recommendations for opt-out HIV testing should be disseminated to HCPs in a broad range of settings. Implementation of system-related factors such as electronic reminders and care coordination procedures should be considered, and a social justice commitment among HCPs should be encouraged. PMID- 26272474 TI - A Complete and Accurate Ab Initio Repeat Finding Algorithm. AB - It has become clear that repetitive sequences have played multiple roles in eukaryotic genome evolution including increasing genetic diversity through mutation, changes in gene expression and facilitating generation of novel genes. However, identification of repetitive elements can be difficult in the ab initio manner. Currently, some classical ab initio tools of finding repeats have already presented and compared. The completeness and accuracy of detecting repeats of them are little pool. To this end, we proposed a new ab initio repeat finding tool, named HashRepeatFinder, which is based on hash index and word counting. Furthermore, we assessed the performances of HashRepeatFinder with other two famous tools, such as RepeatScout and Repeatfinder, in human genome data hg19. The results indicated the following three conclusions: (1) The completeness of HashRepeatFinder is the best one among these three compared tools in almost all chromosomes, especially in chr9 (8 times of RepeatScout, 10 times of Repeatfinder); (2) in terms of detecting large repeats, HashRepeatFinder also performed best in all chromosomes, especially in chr3 (24 times of RepeatScout and 250 times of Repeatfinder) and chr19 (12 times of RepeatScout and 60 times of Repeatfinder); (3) in terms of accuracy, HashRepeatFinder can merge the abundant repeats with high accuracy. PMID- 26272475 TI - In Silico Approach to Support that p-Nitrophenol Monooxygenase from Arthrobacter sp. Strain JS443 Catalyzes the Initial Two Sequential Monooxygenations. AB - p-Nitrophenol (PNP), used primarily for manufacturing pesticides and dyes, has been recognized as a priority environmental pollutant. It is therefore important to reduce the input of this toxicant into the environment and to establish approaches for its removal from the contaminated sites. PNP monooxygenase, a novel enzyme from Gram-positive bacteria like Arthrobacter sp. and Bacillus sp., that comprises two components, a flavoprotein reductase and an oxygenase, catalyzes the initial two sequential monooxygenations to convert PNP to trihydroxybenzene. Accurate and reliable prediction of this enzyme-substrate interactions and binding affinity are of vital importance in understanding these catalytic mechanisms of the two sequential reactions. As crystal structure of the enzyme has not yet been published, we built a homology model for PNP monooxygenase using crystallized chlorophenol 4-monooxygenase from Burkholderia cepacia AC1100 (3HWC) as the template. The model was assessed for its reliability using PROCHECK, ERRAT and ProSA. Molecular docking of the physiological substrates, PNP and 4-nitrocatechol (4-NC), was carried out using Glide v5.7 implemented in Maestro v9.2, and the binding energies were calculated to substantiate the prediction. Docking complexes formed by molecular level interactions of PNP monooxygenase-PNP/4-NC without or with the cofactors, FAD and NADH, showed good correlation with the established experimental evidence that the two-component PNP monooxygenase catalyzes both the hydroxylation of PNP and the oxidative release of nitrite from 4-NC in B. sphaericus JS905. Furthermore, molecular dynamics simulations performed for docking complexes using Desmond v3.0 showed stable nature of the interactions as well. PMID- 26272476 TI - A role for E-cadherin in ensuring cohesive migration of a heterogeneous population of non-epithelial cells. AB - Collective cell migration is a key process underlying the morphogenesis of many organs as well as tumour invasion, which very often involves heterogeneous cell populations. Here we investigated how such populations can migrate cohesively in the Drosophila posterior midgut, comprised of epithelial and mesenchymal cells and show a novel role for the epithelial adhesion molecule E-cadherin (E-Cad) in mesenchymal cells. Despite a lack of junctions at the ultrastructure level, reducing E-Cad levels causes mesenchymal cells to detach from one another and from neighbouring epithelial cells; as a result, coordination between the two populations is lost. Moreover, Bazooka and recycling mechanisms are also required for E-Cad accumulation in mesenchymal cells. These results indicate an active role for E-Cad in mediating cohesive and ordered migration of non-epithelial cells, and discount the notion of E-Cad as just an epithelial feature that has to be switched off to enable migration of mesenchymal cells. PMID- 26272478 TI - Operational parameters and their influence on particle-side mass transfer resistance in a packed bed bioreactor. AB - The influence of internal mass transfer on productivity as well as the performance of packed bed bioreactor was determined by varying a number of parameters; chitosan coating, flow rate, glucose concentration and particle size. Saccharomyces cerevisiae cells were immobilized in chitosan and non-chitosan coated alginate beads to demonstrate the effect on particle side mass transfer on substrate consumption time, lag phase and ethanol production. The results indicate that chitosan coating, beads size, glucose concentration and flow rate have a significant effect on lag phase duration. The duration of lag phase for different size of beads (0.8, 2 and 4 mm) decreases by increasing flow rate and by decreasing the size of beads. Moreover, longer lag phase were found at higher glucose medium concentration and also with chitosan coated beads. It was observed that by increasing flow rates; lag phase and glucose consumption time decreased. The reason is due to the reduction of external (fluid side) mass transfer as a result of increase in flow rate as glucose is easily transported to the surface of the beads. Varying the size of beads is an additional factor: as it reduces the internal (particle side) mass transfer by reducing the size of beads. The reason behind this is the distance for reactants to reach active site of catalyst (cells) and the thickness of fluid created layer around alginate beads is reduced. The optimum combination of parameters consisting of smaller beads size (0.8 mm), higher flow rate of 90 ml/min and glucose concentration of 10 g/l were found to be the maximum condition for ethanol production. PMID- 26272477 TI - Squamous cell carcinoma with osteoclast-like giant cells: a morphologically heterologous group including carcinosarcoma and squamous cell carcinoma with stromal changes. AB - Cutaneous squamous cell carcinoma (SCC) with osteoclast-like giant cells (hereafter, osteoclastic cells) is very rare; eight cases have been reported since 2006. Whether the osteoclastic cells represents a reactive or neoplastic change remains a matter of debate. Osteoclastic cells are often observed in the sarcomatous component of cutaneous carcinosarcoma. SCC with osteoclastic cells is a heterogeneous condition that includes SCC with stromal changes containing osteoclastic cells (also known as osteoclast-like giant cell reaction) and carcinosarcoma. In some cases, SCC with an associated osteoclast-like giant cell reaction has been differentiated from carcinosarcoma based on the degree of cytologic atypia in non-epithelial components. We summarized the clinical and histopathologic characteristics of 11 patients of SCC with osteoclastic cells, including our two cases of SCC with an osteoclast-like giant cell reaction and one case of carcinosarcoma. The affected patients were old and more likely to be male (64%). Seven cases (64%) were in the head and neck. Moreover, multiple features of high risk SCC were observed, such as a tumor size greater than 2 cm (56%), moderate or poor differentiation (100%), recurrence (33%) and nodal metastasis (17%) after excision and immunosuppression (27%). Interestingly, half of the previously reported cases of SCC with osteoclastic giant cell reaction had histopathologic findings that were overlapping with those of carcinosarcoma. PMID- 26272480 TI - Effect of the salts of deep ocean water on the production of cordycepin and adenosine of Cordyceps militaris-fermented product. AB - Cordyceps militaris is a type of entomogenous fungi and has been widely used as a medicinal fungus in Asia. Cordycepin produced by C. militaris has also been found to protect the liver. Moreover, deep ocean water (DOW) was proven to increase the functional compounds of functional fungi-fermented products. However, the regulation of the metals in DOW is still unclear. Therefore, this study investigated the effect of DOW and certain major ions on the production of cordycepin and adenosine of C. militaris. The results indicated that, compared with using ultra-pure water (UPW), using DOW to cultivate C. militaris in a submerged culture increases the production of biomass and adenosine (p < 0.05). In the results of solid culture, the concentration of DOW exhibits a dose effect on cordycepin production. DOW contains ions that can improve the effectiveness of cordycepin, such as Mg(2+), Na(+), Ca(2+), Fe(2+), and NO3 (-), whereas the ion Cl(-) features an inhibitory effect. Moreover, Mg(2+), Na(+), K(+), Ca(2+), Fe(2+), and SO4 (2-)can increase the production of adenosine, whereas Cl(-) cannot. However, the synthetic water made from various types of sodium salts (MgCl2, NaCl, KCl, CaCl2, FeCl2) had nearly the same effect on cordycepin production as that of DOW. PMID- 26272479 TI - Fast and efficient three-step target-specific curing of a virulence plasmid in Salmonella enterica. AB - Virulence plasmids borne by serovars of Salmonella enterica carry genes involved in its pathogenicity, as well as other functions. Characterization of phenotypes associated with virulence plasmids requires a system for efficiently curing strains of their virulence plasmids. Here, we developed a 3-step protocol for targeted curing of virulence plasmids. The protocol involves insertion of an I SecI restriction site linked to an antibiotic resistance gene into the target plasmid using lambda-Red mutagenesis, followed by the transformation with a temperature-sensitive auxiliary plasmid which carries I-SecI nuclease expressed from a tetracycline-inducible promoter. Finally, the auxiliary plasmid is removed by incubation at 42 degrees C and the plasmid-less strains are verified on antibiotic-containing media. This method is fast and very efficient: over 90 % of recovered colonies lacked their virulence plasmid. PMID- 26272482 TI - Poor graft function can be durably and safely improved by CD34+-selected stem cell boosts after allogeneic unrelated matched or mismatched hematopoietic cell transplantation. AB - PURPOSE: Insufficient production of leukocytes, thrombocytes and erythrocytes after allogeneic peripheral blood stem cell transplantation (PBSCT) represents a life-threatening complication. METHODS: In 20 adult patients with poor graft function (PGF defined as transfusion-dependent platelet counts <20,000/ul, or leukocytes <1500/ul, or transfusion-dependent anemia) and variable causes of PGF after allogeneic PBSCT, immunomagnetically selected CD34(+) stem cell boosts (SCB) from matched unrelated (n = 8), mismatched unrelated (n = 11) or haploidentical (n = 1) donors were applied without prior conditioning. RESULTS: Patients received a median of 4.6 * 10(6) CD34(+) cells per kilogram bodyweight (1.9-9.1 * 10(6)) and low T cell numbers (median 0.2 * 10(4), range 0.04-0.6 * 10(4)). All patients showed responses in at least one hematopoietic lineage. Engraftment for platelets, leukocytes and hemoglobin was 88, 88 and 100 % after a median of 14, 13 and 18 days, respectively. With regard to the complete cohort, 90 % (n = 18) showed an increase in platelets (median 76,500/ul, range -7000 to 223,000/ul), 95 % (n = 19) had an increase in leukocytes (median 3110/ul, range 150-13,740/ul) and 90 % (n = 18) improved with regard to hemoglobin (median 1.9 g/dl, range -0.9 to 5.1 g/dl). Due to effective T cell depletion, only one patient developed graft versus host disease (GvHD, grade III) after SCB. Patients were followed for a median of 7.5 months (1-74 months) with 11 patients being alive and disease free with normalized peripheral blood counts at the end of follow-up. CONCLUSIONS: CD34(+)-selected SCB are safe and effective and can durably improve PGF even in patients receiving grafts from unrelated matched or mismatched donors with low incidence of GvHD. PMID- 26272481 TI - Thinking Styles and University Self-Efficacy Among Deaf, Hard-of-Hearing, and Hearing Students. AB - This study explores how students' thinking styles are related to their university self-efficacy, by administering the Thinking Styles Inventory-Revised II and the University Self-Efficacy Scale to 366 deaf or hard-of-hearing (DHH) and 467 hearing university students in mainland China. Results showed that, among all participants, those with Type I styles (i.e., more creativity-generating, less structured, and cognitively more complex) had higher levels of university self efficacy. At the same time, DHH students with Type II styles (i.e., more norm favoring, more structured, and cognitively more simplistic) had lower levels of university self-efficacy. The contributions, limitations, and implications of the present research are discussed. PMID- 26272484 TI - Structural and biochemical characterization of GTP cyclohydrolase II from Helicobacter pylori reveals its redox dependent catalytic activity. AB - GTP cyclohydrolase II (GCHII), catalyzes the conversion of GTP to 2,5-diamino-6 beta-ribosyl-4(3H)-pyrimidinone-5'-phosphate and has been shown to be essential for pathogens. Here we describe the biochemical, kinetic and structural characterization of GCHII from Helicobacter pylori (hGCHII). The crystal structure of hGCHII, unlike other GCHII structures, revealed that cysteines at the active site existed in oxidized state forming two disulfide bonds and lacked Zn(2+) that was shown to be indispensable for catalytic activity in other species. However, incubation of hGCHII with hydrogen peroxide, an oxidizing agent, followed by PAR-assay showed that Zn(2+) was intrinsically present, indicating that all cysteines at the catalytic site remained in reduced state. Moreover, site directed mutagenesis of catalytic site cysteines revealed that only three, out of four cysteines were essential for hGCHII activity. These results, though, indicated that hGCHII crystallized in oxidized form, the expulsion of Zn(2+) upon oxidation of catalytic cysteines revealed its ability to act in response to the redox environment. Exploring further, incubation of hGCHII with reversible thiol modifying agent S-methyl-methane-thiosulfonate resulted in loss of GCHII activity due to oxidation of its cysteine residues as revealed by mass spectrometry studies. However, addition of reducing agent DTT partially restored the hGCHII catalytic activity. Taken together, these results demonstrate that hGCHII can regulate its catalytic activity depending on the redox environment, a function hitherto unknown for GCHII. PMID- 26272485 TI - Is left upper lobectomy for lung cancer a risk factor for cerebral infarction? AB - PURPOSE: Cerebral infarction is a rare complication of lung resection that can result in severe sequelae. Our aim was to investigate the characteristics of patients who suffer from cerebral infarction after surgery for lung cancer. METHODS: We retrospectively reviewed all patients who underwent resection of at least a single lobe for lung cancer at our institution between January 2008 and October 2013. We compared the patients who presented with cerebral infarction with those patients who did not within 30 days of surgery. RESULTS: A total of 562 patients underwent surgery, with five males and one female subsequently experiencing cerebral infarction. Five patients underwent left upper lobectomy and one underwent left lower lobectomy. Patient age, sex, body mass index, smoking index, and operative time were not significantly different between the six patients with postoperative cerebral infarction and the other 556 patients; only the type of operative procedure was significantly different (p < 0.001). Contrast-enhanced computed tomography revealed thrombosis in the stump of the left superior pulmonary vein in patients with postoperative cerebral infarction. CONCLUSIONS: Cerebral infarction occurs at a high frequency in patients who undergo left upper lobectomy for lung cancer. Thrombosis in the left superior pulmonary-vein stump might cause cerebral infarction. PMID- 26272486 TI - Clinical importance of a transcription reverse-transcription concerted (TRC) diagnosis using peritoneal lavage fluids obtained pre- and post-lymphadenectomy from gastric cancer patients. AB - PURPOSE: Our previous study demonstrated that a transcription reverse transcription concerted (TRC) diagnosis using peritoneal lavage fluids at laparotomy was a potential prognostic factor for gastric cancer patients; however, the clinical importance of a TRC diagnosis from peritoneal lavage fluids after lymphadenectomy remains unclear. METHODS: TRC amplification targeting CEA mRNA was utilized to detect free cancer cells before and after lymphadenectomy during gastric cancer resection. Of 120 patients who underwent curative gastrectomy for cT2-T4 gastric cancer, 38 whose peritoneal lavage samples were collected pre- and post-lymphadenectomy were eligible for analysis. RESULTS: Six (16.0 %) patients had CEA positivity before lymphadenectomy (pre-CEA), whereas nine (23.7 %) had CEA positivity after lymphadenectomy (post-CEA). Post-CEA was significantly correlated with higher pathological N-stage. Moreover, the positive post-CEA group had significantly worse relapse-free survival than the negative post-CEA group (p = 0.001). Cox multivariate analysis revealed that post-CEA positivity was a significant predictor of poor relapse-free survival (p = 0.012). It was also a predictor of distant metastasis, but not specific for peritoneal recurrence. CONCLUSIONS: These findings demonstrated that post-CEA positivity in a TRC diagnosis was a potential predictor of disease recurrence, but not a specific predictor of peritoneal recurrence. PMID- 26272487 TI - The D173G mutation in ADAMTS-13 causes a severe form of congenital thrombotic thrombocytopenic purpura. A clinical, biochemical and in silico study. AB - Congenital thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy, inherited with autosomal recessive mode as a dysfunction or severe deficiency of ADAMTS-13 (A Disintegrin And Metalloprotease with ThromboSpondin 1 repeats Nr. 13), caused by mutations in the ADAMTS-13 gene. About 100 mutations of the ADAMTS-13 gene were identified so far, although only a few characterised by in vitro expression studies. A new Asp to Gly homozygous mutation at position 173 of ADAMTS-13 sequence was identified in a family of Romanian origin, with some members affected by clinical signs of TTP. In two male sons, this mutation caused a severe (< 3%) deficiency of ADAMTS-13 activity and antigen level, associated with periodic thrombocytopenia, haemolytic anaemia and mild mental confusion. Both parents, who are cousins, showed the same mutation in heterozygous form. Expression studies of the mutant ADAMTS-13, performed in HEK293 cells, showed a severe decrease of the enzyme's activity and secretion, although the protease was detected inside the cells. Molecular dynamics found that in the D173G mutant the interface area between the metalloprotease domain and the disintegrin-like domain significantly decreases during the simulations, while the proline-rich 20 residues linker region (LR, 285-304) between them undergoes extensive conformational changes. Inter-domain contacts are also significantly less conserved in the mutant compared to the wild-type. Both a decrease of the inter-domain contacts along with a substantial conformational rearrangement of LR interfere with the proper maturation and folding of the mutant ADAMTS-13, thus impairing its secretion. PMID- 26272488 TI - Heart rate variability as a transdiagnostic biomarker of psychopathology. AB - The Research Domain Criteria (RDoC), developed by the National Institute of Mental Health as a neuroscience-informed alternative to traditional psychiatric nosology, is an explicitly dimensional system in which classification of psychopathology is derived inductively (i.e., from basic science), across multiple levels of analysis (e.g., genetic, neural, psychophysiological, and behavioral). Although RDoC is often presented as paradigmatically revolutionary, a review of the history of psychophysiology suggests that roots of RDoC thinking extend at least as far back as the mid-20th Century. In this paper, we briefly and selectively review the historical emergence of neurobiologically-informed dimensional trait models of psychopathology, and we summarize our thinking regarding high frequency heart rate variability (HF-HRV) as a transdiagnostic biomarker of self-regulation and cognitive control. When functional interactions between HF-HRV and systems of behavioral approach and avoidance are considered, diverse patterns of behavioral maladjustment can be subsumed into a single model. This model accommodates the general bifactor structure of psychopathology, and suggests that HF-HRV can be viewed as an autonomic, transdiagnostic biomarker of mental illness. PMID- 26272489 TI - Clinically-indicated replacement versus routine replacement of peripheral venous catheters. AB - BACKGROUND: US Centers for Disease Control guidelines recommend replacement of peripheral intravenous (IV) catheters no more frequently than every 72 to 96 hours. Routine replacement is thought to reduce the risk of phlebitis and bloodstream infection. Catheter insertion is an unpleasant experience for patients and replacement may be unnecessary if the catheter remains functional and there are no signs of inflammation. Costs associated with routine replacement may be considerable. This is an update of a review first published in 2010. OBJECTIVES: To assess the effects of removing peripheral IV catheters when clinically indicated compared with removing and re-siting the catheter routinely. SEARCH METHODS: For this update the Cochrane Vascular Trials Search Co-ordinator searched the Cochrane Vascular Specialised Register (March 2015) and CENTRAL (2015, Issue 3). We also searched clinical trials registries (April 2015). SELECTION CRITERIA: Randomised controlled trials that compared routine removal of peripheral IV catheters with removal only when clinically indicated in hospitalised or community dwelling patients receiving continuous or intermittent infusions. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: Seven trials with a total of 4895 patients were included in the review. The quality of the evidence was high for most outcomes but was downgraded to moderate for the outcome catheter-related bloodstream infection (CRBSI). The downgrade was due to wide confidence intervals, which created a high level of uncertainty around the effect estimate. CRBSI was assessed in five trials (4806 patients). There was no significant between group difference in the CRBSI rate (clinically-indicated 1/2365; routine change 2/2441). The risk ratio (RR) was 0.61 (95% CI 0.08 to 4.68; P = 0.64). No difference in phlebitis rates was found whether catheters were changed according to clinical indications or routinely (clinically-indicated 186/2365; 3-day change 166/2441; RR 1.14, 95% CI 0.93 to 1.39). This result was unaffected by whether infusion through the catheter was continuous or intermittent. We also analysed the data by number of device days and again no differences between groups were observed (RR 1.03, 95% CI 0.84 to 1.27; P = 0.75). One trial assessed all-cause bloodstream infection. There was no difference in this outcome between the two groups (clinically-indicated 4/1593 (0.02%); routine change 9/1690 (0.05%); P = 0.21). Cannulation costs were lower by approximately AUD 7.00 in the clinically-indicated group (mean difference (MD) -6.96, 95% CI -9.05 to -4.86; P <= 0.00001). AUTHORS' CONCLUSIONS: The review found no evidence to support changing catheters every 72 to 96 hours. Consequently, healthcare organisations may consider changing to a policy whereby catheters are changed only if clinically indicated. This would provide significant cost savings and would spare patients the unnecessary pain of routine re-sites in the absence of clinical indications. To minimise peripheral catheter related complications, the insertion site should be inspected at each shift change and the catheter removed if signs of inflammation, infiltration, or blockage are present. PMID- 26272490 TI - Crowdsourcing to Curb Bad Science. PMID- 26272491 TI - Adaptive Immune Resistance: How Cancer Protects from Immune Attack. AB - Adaptive immune resistance is a process in which the cancer changes its phenotype in response to a cytotoxic or proinflammatory immune response, thereby evading it. This adaptive process is triggered by the specific recognition of cancer cells by T cells, which leads to the production of immune-activating cytokines. Cancers then hijack mechanisms developed to limit inflammatory and immune responses and protect themselves from the T-cell attack. Inhibiting adaptive immune resistance is the mechanistic basis of responses to PD-1 or PD-L1-blocking antibodies, and may be of relevance for the development of other cancer immunotherapy strategies. SIGNIFICANCE: Several new immunotherapy strategies to treat cancer are based on inhibiting processes through which cancer adapts and evades from an immune response. Recognizing the specific adaptive resistance mechanisms in each case is likely to allow the personalized development of immunotherapies tailored to block how a particular cancer protects itself from the immune system. PMID- 26272497 TI - A nanopore membrane regulator device for laser modulated flow after glaucoma surgery. AB - Glaucoma, the second most common cause of blindness in the world, is a multifactorial disease with several risk factors, of which intraocular pressure (IOP) is a primary contributing factor. Filtration surgery is one of the most effective means to significantly lower IOP compared to medical or laser treatments, and it is typically reserved for advanced disease. However, there are high rates of postoperative complications associated with the procedure, often from over- or under-filtration. To address these problems, the glaucoma drainage device regulator (GDDR) implant was developed to allow post-operative control of aqueous flow and IOP. The device, a tube with a nanopore membrane, is placed beneath the scleral flap. Postoperatively, the membrane surface can be ruptured with a laser to augment flow through the system. This feature allows adjustable control of aqueous flow and diminishes the risk of hypotony in the early postoperative period. PMID- 26272496 TI - Integrated analysis of miRNA/mRNA network in placenta identifies key factors associated with labor onset of Large White and Qingping sows. AB - Labour onset is a very complex physiological process, and its mechanism is poorly understood. Here, we obtained the mRNA and miRNA expression profiles from the placentas of four groups of sows: Qingping sows 112 days after insemination with signs of labour onset (QS), Qingping sows 114 days after insemination with signs of labour onset (QL), Large White sows 114 days after insemination with signs of labour onset (LL) and Large White sows 112 days after insemination without signs of labour onset (LN). A set of differentially expressed genes, including 2164 mRNAs and 39 miRNAs, were found. A DAVID analysis of these differentially expressed genes revealed their critical roles in response to hormone stimulus, immune response. Cytoscape Network analysis of the functional genes found node mRNAs and that the regulatory network between the node mRNAs and miRNAs was established. A comparison of the sequencing data from the shorter gestation period (QS) and the normal gestation period (QL) indicated that these genes were responsible for the quicker and more sensitive reaction to the regulation of labour onset. This research not only detected the key factors that were involved in labour onset but also provided useful information for the research of gynaecological diseases. PMID- 26272498 TI - Reality and understanding of asthma control. AB - The aim of this study was to describe the level and perception of control in severe asthma in Trinidad after the introduction of revised guidelines for asthma management. Adult asthmatics (N = 329) at Trinidad's chest clinics were cross sectionally examined for guideline-defined disease control. Patients' mean (SD) age was 54.36 (14.9) years, with body mass index = 28.54 (7.4) kg/meter(2), and females were proportionally more (246, 74.74%). Measured (45.29%) and perceived (18.96%) uncontrolled disease were poorly concordant (kappa statistic = 0.197). Co-morbidity (>=2 conditions) correlated with uncontrolled disease in 55.80% of patients (Spearman correlation p = 0.03). Absolute peak expiratory flow was higher (p < 0.001) in controlled and/or partially controlled disease than in uncontrolled asthma. Routine work limitation, night-time disturbances, work absenteeism, exacerbations, rescue inhalation and perceived control correlated with uncontrolled asthma (p < 0.001). Few patients self-monitored lung function (9.73%) or kept an asthma diary (6.69%), but 65.1% believed they had to live with their symptoms. The asthma burden was at least one hospitalization (53.80%) and emergency department visit (66.36%) in the past year, cough (74.49%), dyspnoea (84.50%), wheezing (80.55%) and chest tightness (66.87%). After the revised guidelines, uncontrolled asthma and related morbidity remain suboptimal, with disagreeing actual and perceived control. Efforts to transform guidelines into patient care with realistic interpretation of control are recommended. PMID- 26272499 TI - Patient agenda setting in respiratory outpatients: A randomized controlled trial. AB - Soliciting a patient's agenda (the reason for their visit, concerns and expectations) is fundamental to health care but if not done effectively outcomes can be adversely affected. Forms to help patients consider important issues prior to a consultation have been tested with mixed results. We hypothesized that using an agenda form would impact the extent to which patients felt their doctor discussed the issues that were important to them. Patients were randomized to receive an agenda form to complete whilst waiting or usual care. The primary outcome measure was the proportion of patients agreeing with the statement 'My doctor discussed the issues that were important to me' rated on a four-point scale. Secondary outcomes included other experience and satisfaction measures, consultation duration and patient confidence. There was no significant effect of agenda form use on primary or secondary outcomes. Post hoc exploratory analyses suggested possible differential effects for new compared to follow-up patients. There was no overall benefit from the form and a risk of detrimental impact on patient experience for some patients. There is a need for greater understanding of what works for whom in supporting patients to get the most from their consultation. PMID- 26272500 TI - Acute responses to exercise training and relationship with exercise adherence in moderate chronic obstructive pulmonary disease. AB - The objectives of our study were to (i) compare, in chronic obstructive pulmonary disease (COPD) patients, acute responses to continuous training at high intensity (CTHI), continuous training at ventilatory threshold (CTVT) and interval training (IT); (ii) examine associations between acute responses and 12-week adherence; and (iii) investigate whether the relationship between acute responses and adherence is mediated/moderated by affect/vigour. Thirty-five COPD patients (forced expiratory volume in 1 second = 60.2 +/- 15.8% predicted), underwent baseline assessments, were randomly assigned to CTHI, CTVT or IT, were monitored throughout about before training, and underwent 12 weeks of exercise training during which adherence was tracked. Compared with CTHI, CTVT was associated with lower respiratory exchange ratio, heart rate and respiratory rate (RR), while IT induced higher [Formula: see text], [Formula: see text]maximal voluntary ventilation, RR and lower pulse oxygen saturation. From pre- to post-exercise, positive affect increased (F = 9.74, p < 0.001) and negative affect decreased (F = 6.43, p = 0.005) across groups. CTVT reported greater end-exercise vigour compared to CTHI (p = 0.01) and IT (p = 0.02). IT exhibited lowest post-exercise vigour (p = 0.04 versus CTHI, p = 0.02 versus CTVT) and adherence rate (F = 6.69, p = 0.004). Mean [Formula: see text] (r = -0.466, p = 0.007) and end-exercise vigour (r = 0.420, p = 0.017) were most strongly correlated with adherence. End exercise vigour moderated the relationship between [Formula: see text] and adherence (beta = 2.74, t(32) = 2.32, p = 0.03). In summary, CTHI, CTVT and IT improved affective valence from rest to post-exercise and induced a significant 12-week exercise training effect. However, they elicited different acute physiological responses, which in turn were associated with differences in 12 week adherence to the target training intensity. This association was moderated by acute end-exercise vigour. PMID- 26272501 TI - Information behaviour of French-speaking speech-language therapists in Belgium: results of a questionnaire survey. AB - BACKGROUND: Speech-language therapists (SLTs) are encouraged to implement evidence-based practice (EBP). Nevertheless, EBP use by practitioners can be questioned. OBJECTIVES: The objective of this study was to explore Belgian French speaking SLTs' information behaviour and their awareness of EBP. The collected data allow one to determine how far they have embraced this approach. METHODS: The two Belgian French-speaking SLT professional associations promoted an online questionnaire survey by email. Additionally, clinical supervisors of students were asked to participate. In March 2012, 2068 emails were sent. RESULTS: The participation rate was at least 20% (n = 415). The reported information needs mainly concerned treatment or diagnosis. Most of the time, to attempt to fulfil their information needs, SLTs relied on their own resources (personal experience and libraries) and on colleagues in the workplace. When they searched on the Internet, they preferred to use a general search engine rather than a specialised bibliographic database. Barriers to obtaining scientific information are highlighted. Only 12% of the respondents had already heard about EBP. CONCLUSION: This study provides the first overview of the information behaviour of SLTs working in the French community of Belgium. Several recommendations are suggested for SLTs and librarians. PMID- 26272502 TI - Predictive habitat suitability models to aid conservation of elasmobranch diversity in the central Mediterranean Sea. AB - Commercial fisheries have dramatically impacted elasmobranch populations worldwide. With high capture and bycatch rates, the abundance of many species is rapidly declining and around a quarter of the world's sharks and rays are threatened with extinction. At a regional scale this negative trend has also been evidenced in the central Mediterranean Sea, where bottom-trawl fisheries have affected the biomass of certain rays (e.g. Raja clavata) and sharks (e.g. Mustelus spp.). Detailed knowledge of elasmobranch habitat requirements is essential for biodiversity conservation and fisheries management, but this is often hampered by a poor understanding of their spatial ecology. Habitat suitability models were used to investigate the habitat preference of nine elasmobranch species and their overall diversity (number of species) in relation to five environmental predictors (i.e. depth, sea surface temperature, surface salinity, slope and rugosity) in the central Mediterranean Sea. Results showed that depth, seafloor morphology and sea surface temperature were the main drivers for elasmobranch habitat suitability. Predictive distribution maps revealed different species-specific patterns of suitable habitat while high assemblage diversity was predicted in deeper offshore waters (400-800 m depth). This study helps to identify priority conservation areas and diversity hot-spots for rare and endangered elasmobranchs in the Mediterranean Sea. PMID- 26272503 TI - Pathological and bacteriological characterization of neonatal porcine diarrhoea of uncertain aetiology. AB - Neonatal porcine diarrhoea of uncertain aetiology has been reported from a number of countries. This study investigated 50 diarrhoeic and 19 healthy piglets from 10 affected Swedish herds. The piglets were blood-sampled for analysis of serum gamma-globulin and necropsied, and the intestines were sampled for histopathology and cultured for Escherichia coli, Clostridium perfringens and Clostridium difficile. Escherichia coli isolates (n = 276) were examined by PCR for virulence genes encoding LT, STa, STb, EAST1, VT2e, F4, F5, F6, F18, F41, AIDA-I, intimin, and for the genes aaiC and aggR. Selected isolates were analysed for additional virulence genes by a microarray and subjected to O-typing. Clostridium perfringens isolates (n = 152) were examined by PCR for genes encoding major toxins, enterotoxin and beta2-toxin. There was no difference in serum gamma globulin concentration between diarrhoeic and non-diarrhoeic piglets, and pathological lesions in the intestines were generally mild. Porcine enterotoxigenic Escherichia coli, a common cause of piglet diarrhoea, was only found in two piglets. Further, the virulence gene profiling did not suggest involvement of other diarrhoeogenic pathotypes of Escherichia coli. Growth of Clostridium perfringens did not differ between diarrhoeic and non-diarrhoeic piglets. All isolates were type A, all were negative for enterotoxin, and 151 of 152 isolates were beta2-toxin positive. In pigs >= 2 days old, moderate to profuse growth of Clostridium difficile was more common in the controls. In conclusion, it was not possible to relate Escherichia coli, Clostridium perfringens type A and C or Clostridium difficile to neonatal porcine diarrhoea in any of the investigated herds. PMID- 26272505 TI - Corrigendum: Long-term efficacy and safety of omalizumab in patients with persistent uncontrolled allergic asthma: a systematic review and meta-analysis. PMID- 26272506 TI - The public's voice about healthcare quality regulation policies. A population based survey. AB - BACKGROUND: In the wake of various high-profile incidents in a number of countries, regulators of healthcare quality have been criticised for their 'soft' approach. In politics, concerns were expressed about public confidence. It was claimed that there are discrepancies between public opinions related to values and the values guiding regulation policies. Although the general public are final clients of regulators' work, their opinion has only been discussed in research to a limited extent. The aim of this study is to explore possible discrepancies between public values and opinions and current healthcare quality regulation policies. METHODS: A questionnaire was submitted to 1500 members of the Dutch Healthcare Consumer Panel. Questions were developed around central ideas underlying healthcare quality regulation policies. RESULTS: The response rate was 58.3%. The regulator was seen as being more responsible for quality of care than care providers. Patients were rated as having the least responsibility. Similar patterns were observed for the food service industry and the education sector. Complaints by patients' associations were seen as an important source of information for quality regulation, while fewer respondents trusted information delivered by care providers. However, respondents supported the regulator's imposition of lighter measures firstly. CONCLUSIONS: There are discrepancies and similarities between public opinion and regulation policies. The discrepancies correspond to fundamental concepts; decentralisation of responsibilities is not what the public wants. There is little confidence in the regulator's use of information obtained by care providers' internal monitoring, while a larger role is seen for complaints of patient organisations. This discrepancy seems not to exist regarding the regulator's approach of imposing measures. A gradual, and often soft approach, is favoured by the majority of the public in spite of the criticism that is voiced in the media regarding this approach. Our study contributes to the limited knowledge of public opinion on government regulation policies. This knowledge is needed in order to effectively assess different approaches to involve the public in regulation policies. PMID- 26272507 TI - A Nonstationary Markov Model Detects Directional Evolution in Hymenopteran Morphology. AB - Directional evolution has played an important role in shaping the morphological, ecological, and molecular diversity of life. However, standard substitution models assume stationarity of the evolutionary process over the time scale examined, thus impeding the study of directionality. Here we explore a simple, nonstationary model of evolution for discrete data, which assumes that the state frequencies at the root differ from the equilibrium frequencies of the homogeneous evolutionary process along the rest of the tree (i.e., the process is nonstationary, nonreversible, but homogeneous). Within this framework, we develop a Bayesian approach for testing directional versus stationary evolution using a reversible-jump algorithm. Simulations show that when only data from extant taxa are available, the success in inferring directionality is strongly dependent on the evolutionary rate, the shape of the tree, the relative branch lengths, and the number of taxa. Given suitable evolutionary rates (0.1-0.5 expected substitutions between root and tips), accounting for directionality improves tree inference and often allows correct rooting of the tree without the use of an outgroup. As an empirical test, we apply our method to study directional evolution in hymenopteran morphology. We focus on three character systems: wing veins, muscles, and sclerites. We find strong support for a trend toward loss of wing veins and muscles, while stationarity cannot be ruled out for sclerites. Adding fossil and time information in a total-evidence dating approach, we show that accounting for directionality results in more precise estimates not only of the ancestral state at the root of the tree, but also of the divergence times. Our model relaxes the assumption of stationarity and reversibility by adding a minimum of additional parameters, and is thus well suited to studying the nature of the evolutionary process in data sets of limited size, such as morphology and ecology. PMID- 26272508 TI - Digital technologies for cognitive assessment to accelerate drug development in Alzheimer's disease. AB - For many neurological and psychiatric diseases, novel therapeutics have been elusive for decades. By focusing on attention interference in Alzheimer's disease (AD), we provide a future vision on how emerging mobile, computer, and device based cognitive tools are converting classically noisy, subjective, data-poor clinical endpoints associated with neuropsychiatric disease assessment into a richer, scalable, and objective set of measurements. Incorporation of such endpoints into clinical drug trials holds promise for more quickly and efficiently developing new medicines. PMID- 26272510 TI - Business Modeling to Implement an eHealth Portal for Infection Control: A Reflection on Co-Creation With Stakeholders. AB - BACKGROUND: It is acknowledged that the success and uptake of eHealth improve with the involvement of users and stakeholders to make technology reflect their needs. Involving stakeholders in implementation research is thus a crucial element in developing eHealth technology. Business modeling is an approach to guide implementation research for eHealth. Stakeholders are involved in business modeling by identifying relevant stakeholders, conducting value co-creation dialogs, and co-creating a business model. Because implementation activities are often underestimated as a crucial step while developing eHealth, comprehensive and applicable approaches geared toward business modeling in eHealth are scarce. OBJECTIVE: This paper demonstrates the potential of several stakeholder-oriented analysis methods and their practical application was demonstrated using Infectionmanager as an example case. In this paper, we aim to demonstrate how business modeling, with the focus on stakeholder involvement, is used to co create an eHealth implementation. METHODS: We divided business modeling in 4 main research steps. As part of stakeholder identification, we performed literature scans, expert recommendations, and snowball sampling (Step 1). For stakeholder analyzes, we performed "basic stakeholder analysis," stakeholder salience, and ranking/analytic hierarchy process (Step 2). For value co-creation dialogs, we performed a process analysis and stakeholder interviews based on the business model canvas (Step 3). Finally, for business model generation, we combined all findings into the business model canvas (Step 4). RESULTS: Based on the applied methods, we synthesized a step-by-step guide for business modeling with stakeholder-oriented analysis methods that we consider suitable for implementing eHealth. CONCLUSIONS: The step-by-step guide for business modeling with stakeholder involvement enables eHealth researchers to apply a systematic and multidisciplinary, co-creative approach for implementing eHealth. Business modeling becomes an active part in the entire development process of eHealth and starts an early focus on implementation, in which stakeholders help to co-create the basis necessary for a satisfying success and uptake of the eHealth technology. PMID- 26272509 TI - A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. AB - Test systems to identify developmental toxicants are urgently needed. A combination of human stem cell technology and transcriptome analysis was to provide a proof of concept that toxicants with a related mode of action can be identified and grouped for read-across. We chose a test system of developmental toxicity, related to the generation of neuroectoderm from pluripotent stem cells (UKN1), and exposed cells for 6 days to the histone deacetylase inhibitors (HDACi) valproic acid, trichostatin A, vorinostat, belinostat, panobinostat and entinostat. To provide insight into their toxic action, we identified HDACi consensus genes, assigned them to superordinate biological processes and mapped them to a human transcription factor network constructed from hundreds of transcriptome data sets. We also tested a heterogeneous group of 'mercurials' (methylmercury, thimerosal, mercury(II)chloride, mercury(II)bromide, 4 chloromercuribenzoic acid, phenylmercuric acid). Microarray data were compared at the highest non-cytotoxic concentration for all 12 toxicants. A support vector machine (SVM)-based classifier predicted all HDACi correctly. For validation, the classifier was applied to legacy data sets of HDACi, and for each exposure situation, the SVM predictions correlated with the developmental toxicity. Finally, optimization of the classifier based on 100 probe sets showed that eight genes (F2RL2, TFAP2B, EDNRA, FOXD3, SIX3, MT1E, ETS1 and LHX2) are sufficient to separate HDACi from mercurials. Our data demonstrate how human stem cells and transcriptome analysis can be combined for mechanistic grouping and prediction of toxicants. Extension of this concept to mechanisms beyond HDACi would allow prediction of human developmental toxicity hazard of unknown compounds with the UKN1 test system. PMID- 26272511 TI - Perceived learned skills and professional development of graduates from a master in dental public health programme. AB - INTRODUCTION: Assessing the impact of a training programme is important for quality assurance and further development. It also can helps with accountability and marketing purposes. This study evaluated the impact of King's College London (KCL) Master of Science programme in Dental Public Health in terms of graduates' perceived learned skills and professional development. METHODS: An online questionnaire was sent to individuals who completed successfully the KCL Master of Science programme in Dental Public Health and had a valid email address. Participants provided information on demographic characteristics, perceived learned skills (intellectual, practical and generic) and professional development (type of organisation, position in the organisation and functions performed at work before and after the programme). Learned skills' scores were compared by demographic factors in multiple linear regression models, and the distribution of responses on career development was compared using nonparametric tests for paired groups. RESULTS: Although all scores on learned skills were on the favourable side of the Likert scale, graduates reported higher scores for practical skills, followed by intellectual and generic skills. No differences in scores were found by sex, age, nationality or time since graduation. In terms of career development, there were significantly higher proportions of graduates working in higher education institutions and taking leadership/managerial roles in organisations as well as greater number and variety of functions at work after than before the programme. CONCLUSION: This online survey shows that the programme has had a positive impact on graduates in terms of perceived learned skills and professional development. PMID- 26272512 TI - Effect of sex, dietary glycerol or dietary fat during late fattening, on fatty acid composition and positional distribution of fatty acids within the triglyceride in pigs. AB - The effect of sex, source of saturated fat (lard v. palm oil) and glycerol inclusion in the fattening diet on composition and fatty acid positional distribution in the triglyceride molecule was studied in pigs from 78 to 110 kg BW. Average daily gain and carcass characteristics, including ham and loin weight, were not affected by dietary treatment but sex affected backfat depth (P < 0.01). A significant interaction between sex and glycerol inclusion was observed; dietary glycerol increased lean content in gilts but not in barrows (P < 0.05 for the interaction). Individual and total saturated fatty acid (SFA) concentrations were greater in barrows than in gilts. In contrast, the concentration of total polyunsaturated fatty acids (PUFA) and of C18:2n-6, C18:3n 3, C20:3n-9 and C20:4n-6 in the intramuscular fat (IMF) was higher (P < 0.05) in gilts than in barrows. Sex did not affect total monounsaturated fatty acids (MUFA) concentration in the IMF. The proportion of SFA in the subcutaneous fat (SF) was higher in barrows than in gilts (P < 0.001). Within the individual SFA, sex affected only the concentrations of C14:0 and C16:0 (P < 0.001). Dietary fat did not affect total SFA or PUFA concentrations of the IMF but the subcutaneous total MUFA concentration tended to be higher (P = 0.079) in pigs fed lard than in pigs fed palm oil. Dietary glycerol increased total MUFA and C18:1n-9 concentration in the IMF and increased total MUFA and decreased C18:2n-6, C18:3n 3 and total PUFA concentrations in the SF. The data indicate that altering the fatty acid composition of the triglyceride molecule at the 2-position, by dietary intervention during the fattening phase, is very limited. PMID- 26272514 TI - A pentacene monolayer trapped between graphene and a substrate. AB - A self-assembled pentacene monolayer can be fabricated between the solid-solid interface of few-layered graphene (FLG) and the mica substrate, through a diffusion-spreading method. By utilizing a transfer method that allows us to sandwich pentacene between graphene and mica, followed by controlled annealing, we enabled the diffused pentacene to be trapped in the interfaces and led to the formation of a stable monolayer. We found that the formation of a monolayer is kinetically favored by using a 2D Ising lattice gas model for pentacene trapped between the graphene-substrate interfaces. This kinetic Monte Carlo simulation results indicate that, due to the graphene substrate enclosure, the spreading of the first layer proceeds faster than the second layer, as the kinetics favors the filling of voids by molecules from the second layer. This graphene assisted monolayer assembly method provides a new avenue for the fabrication of two dimensional monolayer structures. PMID- 26272515 TI - Arthroscopic Articular Reconstruction of Capitellar Osteochondral Defects. AB - BACKGROUND: Articular reconstruction is recommended for some unstable capitellar osteochondritis dissecans (OCD) lesions. Capitellar osteochondral autograft transplantation (OAT) through an open approach for optimal visualization and perpendicular graft implantation has been advocated. However, arthroscopic capitellar OAT may achieve the same treatment goals with decreased morbidity and ability to treat the entire joint for pathologic changes. PURPOSE/HYPOTHESIS: The purpose of this study was to assess the ability to resurface the capitellum arthroscopically. The hypothesis was that arthroscopy allows sufficient access to facilitate perpendicular graft placement in most clinically significant capitellar OCD lesions. STUDY DESIGN: Descriptive laboratory study. METHODS: Arthroscopy was performed on 12 fresh-frozen cadaveric elbows. Of the tunnels created, 21 were used in final analysis. A 6-mm osteochondral transplantation bone graft harvester was used to generate perpendicular recipient sites in the capitellar articular surface. Both central (n = 11) and lateral (n = 10) OCD locations were studied. Fluoroscopy was used to measure the angle of the harvest relative to the axis of the humerus and tunnel perpendicularity. RESULTS: Among central and lateral lesions, the average (+/-SD) degree of perpendicularity achieved was 85.3 degrees +/- 2.9 degrees and 85.8 degrees +/- 2.5 degrees , respectively. Perpendicular harvests were achieved in central and lateral lesions as high as 74.9 degrees and 80.4 degrees , anterior to the humeral shaft, respectively. No significant relationship was noted between increasing anterior location and ability to attain perpendicular harvests. Achieving perpendicularity in lesions that were more anterior to these values was not possible due to anatomic constraints of the radial head in maximal elbow flexion. CONCLUSION: Adequate recipient tunnels were created in lesions that were as high as 75 degrees to 80 degrees anterior to the humeral shaft, which encompasses most clinically relevant lesions. Moreover, increasing the anterior position of the lesion did not compromise the ability to generate perpendicular tunnels. The findings of this cadaveric study suggest that most clinically relevant capitellar osteochondral lesions can be successfully resurfaced arthroscopically. CLINICAL RELEVANCE: This study demonstrates the feasibility of performing an arthroscopic versus open articular reconstruction when indicated for high-grade capitellar OCD lesions. These conclusions afford sports medicine surgeons another tool in the treatment of this challenging condition. PMID- 26272513 TI - Evaluation of exposure-response relationships for health effects of microbial bioaerosols - A systematic review. AB - Studies suggest adverse health effects following exposure to bioaerosols in the environment and in particular at workplaces. However, there is still a lack of health-related exposure limits based on toxicological or epidemiological studies from environmental health or from the working environment. The aim of this study was to derive health-based exposure limits for bioaerosols that can protect the general population as group "at risk" via environmental exposure using analysis of peer-reviewed studies related to occupational medicine, indoor air and environmental health. The derivation of exposure limits should be conducted by the members of a bioaerosol expert panel according to established toxicological criteria. A systematic review was performed in Medline (PubMed) including studies containing both data on exposure measurements and observed health outcomes. In addition, literature recommended by the experts was considered. A comprehensive search strategy was generated and resulted in a total of n=1569 studies in combination with the literature recommendations. Subsequently, abstracts were screened using defined exclusion criteria yielding a final number of n=44 studies. A standardized extraction sheet was used to combine data on health effects and exposure to different bioaerosols. After full-text screening and extraction according to the defined exclusion criteria n=20 studies were selected all related to occupational exposures comprising the working areas wood processing, farming, waste processing and others. These studies were analyzed in collaboration with the bioaerosol expert network in terms of suitability for derivation of health-related exposure limits. The bioaerosol expert network concluded that none of the analyzed studies provided suitable dose-response relationships for derivation of exposure limits. The main reasons were: (1) lack of studies with valid dose-response data; (2) diversity of employed measuring methods for microorganisms and bioaerosol-emitting facilities; (3) heterogeneity of health effects; (4) insufficient exposure assessment. However, several indicator parameters and exposure concentrations could be identified for different bioaerosol-emitting facilities. Nevertheless, health-related exposure limits are urgently needed especially in approval procedures of facilities like composting plants or livestock farms emitting bioaerosols in the neighbourhood of residents. In the regulatory toxicology framework, it is common to use animal experimental studies for derivation of general exposure limits if appropriate environmental epidemiological studies on harmful substances are lacking. This might be another possibility to obtain health-related exposure limits for specific bioaerosol parameters. Furthermore, we recommend to use suitable measurable outcome parameters related to bioaerosols; to measure bioaerosols according to a protocol representative for exposure pattern and duration at the particular work place; to develop standardized detection methods for indicator parameters; to combine different detection methods to compensate for the limitations of each method; to apply new analysis methods to identify the real risk potential. PMID- 26272516 TI - Deficits in Glenohumeral Passive Range of Motion Increase Risk of Shoulder Injury in Professional Baseball Pitchers: A Prospective Study. AB - BACKGROUND: Shoulder injuries from repetitive baseball pitching continue to be a serious, common problem. PURPOSE: To determine whether passive range of motion of the glenohumeral joint was predictive of shoulder injury or shoulder surgery in professional baseball pitchers. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Passive range of motion of the glenohumeral joint was assessed with a bubble goniometer during spring training for all major and minor league pitchers of a single professional baseball organization over a period of 8 successive seasons (2005-2012). Investigators performed a total of 505 examinations on 296 professional pitchers. Glenohumeral external and internal rotation was assessed with the pitcher supine and the arm abducted to 90 degrees in the scapular plane with the scapula stabilized anteriorly at the coracoid process. Total rotation was defined as the sum of internal and external glenohumeral rotation. Passive shoulder flexion was measured with the pitcher supine and the lateral border of the scapula manually stabilized. After examination, shoulder injuries and injury durations were recorded by each pitcher's respective baseball organization and reported to the league as an injury transaction as each player was placed on the disabled list. RESULTS: Highly significant side-to-side differences were noted within subjects for each range of motion measurement. There were 75 shoulder injuries and 20 surgeries recorded among 51 pitchers, resulting in 5570 total days on the disabled list. Glenohumeral internal rotation deficit, total rotation deficit, and flexion deficit were not significantly related to shoulder injury or surgery. Pitchers with insufficient external rotation (<5 degrees greater external rotation in the throwing shoulder) were 2.2 times more likely to be placed on the disabled list for a shoulder injury (P = .014; 95% CI, 1.2-4.1) and were 4.0 times more likely to require shoulder surgery (P = .009; 95% CI, 1.5 12.6). CONCLUSION: Insufficient shoulder external rotation on the throwing side increased the likelihood of shoulder injury and shoulder surgery. Sports medicine clinicians should be aware of these findings and develop a preventive plan that addresses this study's findings to reduce pitchers' risk of shoulder injury and surgery. PMID- 26272517 TI - European Code against Cancer, 4th Edition: Tobacco and cancer. AB - Tobacco use, and in particular cigarette smoking, is the single largest preventable cause of cancer in the European Union (EU). All tobacco products contain a wide range of carcinogens. The main cancer-causing agents in tobacco smoke are polycyclic aromatic hydrocarbons, tobacco-specific N-nitrosamines, aromatic amines, aldehydes, and certain volatile organic compounds. Tobacco consumers are also exposed to nicotine, leading to tobacco addiction in many users. Cigarette smoking causes cancer in multiple organs and is the main cause of lung cancer, responsible for approximately 82% of cases. In 2012, about 313,000 new cases of lung cancer and 268,000 lung cancer deaths were reported in the EU; 28% of adults in the EU smoked tobacco, and the overall prevalence of current use of smokeless tobacco products was almost 2%. Smokeless tobacco products, a heterogeneous category, are also carcinogenic but cause a lower burden of cancer deaths than tobacco smoking. One low-nitrosamine product, snus, is associated with much lower cancer risk than other smokeless tobacco products. Smoking generates second-hand smoke (SHS), an established cause of lung cancer, and inhalation of SHS by non-smokers is still common in indoor workplaces as well as indoor public places, and more so in the homes of smokers. Several interventions have proved effective for stopping smoking; the most effective intervention is the use of a combination of pharmacotherapy and behavioural support. Scientific evidence leads to the following two recommendations for individual action on tobacco in the 4th edition of the European Code Against Cancer: (1) "Do not smoke. Do not use any form of tobacco"; (2) "Make your home smoke-free. Support smoke-free policies in your workplace". PMID- 26272518 TI - Promoting the early detection of cancer: a systematic review of community pharmacy-based education and screening interventions. AB - BACKGROUND: Given that the burden of cancer is set to increase globally, strategies are needed to improve the early detection of cancer. As such, increasing focus is now placed on promoting the early detection of cancer through education and screening interventions. One healthcare setting that has significant potential in delivering these approaches is the community pharmacy. AIMS: This study aimed to systematically review the literature to identify and assess the current evidence for the role of community pharmacies in delivering early cancer detection initiatives. METHOD: A systematic literature search of four databases was undertaken (Medline, Embase, CINAHL, PsycINFO) from inception to June 2015 to identify peer-reviewed intervention studies. RESULTS: A total of 3711 articles were identified from the search, of which twelve were included in the review. The studies focused on a range of different cancers and showed it is feasible to recruit patients to education and screening interventions within a community pharmacy setting. However, the interventions were poorly described in the literature. CONCLUSION: There is significant potential for community pharmacy to deliver education and screening-based interventions to promote the early detection of cancer, but more evidence is needed to ascertain how interventions delivered in this setting impact on patient outcomes. PMID- 26272519 TI - Unique Toll-Like Receptor 4 Activation by NAMPT/PBEF Induces NFkappaB Signaling and Inflammatory Lung Injury. AB - Ventilator-induced inflammatory lung injury (VILI) is mechanistically linked to increased NAMPT transcription and circulating levels of nicotinamide phosphoribosyl-transferase (NAMPT/PBEF). Although VILI severity is attenuated by reduced NAMPT/PBEF bioavailability, the precise contribution of NAMPT/PBEF and excessive mechanical stress to VILI pathobiology is unknown. We now report that NAMPT/PBEF induces lung NFkappaB transcriptional activities and inflammatory injury via direct ligation of Toll-like receptor 4 (TLR4). Computational analysis demonstrated that NAMPT/PBEF and MD-2, a TLR4-binding protein essential for LPS induced TLR4 activation, share ~30% sequence identity and exhibit striking structural similarity in loop regions critical for MD-2-TLR4 binding. Unlike MD 2, whose TLR4 binding alone is insufficient to initiate TLR4 signaling, NAMPT/PBEF alone produces robust TLR4 activation, likely via a protruding region of NAMPT/PBEF (S402-N412) with structural similarity to LPS. The identification of this unique mode of TLR4 activation by NAMPT/PBEF advances the understanding of innate immunity responses as well as the untoward events associated with mechanical stress-induced lung inflammation. PMID- 26272520 TI - Sinus rhythm R-wave amplitude as a predictor of ventricular fibrillation undersensing in patients with implantable cardioverter-defibrillator. AB - BACKGROUND: Ventricular fibrillation (VF) is induced during implantable cardioverter-defibrillator (ICD) implantation to ensure that the ICD will sense, detect, and defibrillate VF. ICD implant guidelines state that the amplitude of the sinus rhythm R wave recorded from the ventricular electrogram should have amplitude >=5 mV. No study has tested the relationship between sinus rhythm R wave amplitude and VF sensing using modern, transvenous sensing electrodes. OBJECTIVE: The goal of this study was to determine whether there is a sinus rhythm R-wave amplitude cutoff that can be used to determine which patients are not at risk of VF undersensing. METHODS: A retrospective analysis of induced and spontaneous VF episodes from 2 clinical trials with 2022 patients was performed. Episodes with undersensing during the initial detection of VF were identified, and the distribution of sinus rhythm R-wave amplitudes for patients with and without VF undersensing was analyzed. RESULTS: Only 3% of analyzed induced VF episodes were considered to have VF undersensing, and none had clinically significant detection delays. There was no correlation between device-measured, rectified sinus rhythm R-wave amplitude and VF undersensing at the time of implantation or during follow-up, although <4% of patients had sinus rhythm R waves with amplitude <3 mV. CONCLUSION: We analyzed true bipolar sensing of induced VF or spontaneous ventricular tachycardia/VF detected in the ICD VF zone. Sensing of VF was so reliable that clinically significant undersensing did not occur. Our findings do not support any recommended minimum sinus rhythm R wave to ensure reliable sensing of VF or the necessity of inducing VF to verify sensing for rectified sinus rhythm R-waves with amplitude >=3 mV. PMID- 26272521 TI - Effect of mental stress on dynamic electrophysiological properties of the endocardium and epicardium in humans. AB - BACKGROUND: Striking temporal associations exist between ventricular arrhythmia and acute mental stress, for example, during natural disasters, or defibrillator shocks associated with stressful events. We hypothesized that electrophysiological changes in response to mental stress may be exaggerated at short coupling intervals and hence relevant to arrhythmia initiation. OBJECTIVE: The aim of this study was to determine the dynamic response in human electrophysiology during mental stress. METHODS: Patients with normal hearts and supraventricular tachycardia underwent electrophysiological studies avoiding sedation. Conditions of relaxation and stress were induced with standardized psychometric protocols (mental arithmetic and anger recall) during decremental S1S2 right ventricular (RV) pacing. Unipolar electrograms were acquired simultaneously from the RV endocardium, left ventricular (LV) endocardium (LV endo), and epicardium (LV epi), and activation-recovery intervals (ARIs) computed. RESULTS: Twelve patients ( 9 women; median age 34 years) were studied. During stress, effective refractory period (ERP) reduced from 228 +/- 23 to 221 +/- 21 ms (P < .001). ARIs reduced during mental stress (P < .001), with greater reductions in LV endocardium than in the epicardium or RV endocardium (LV endo -8 ms; LV epi -5 ms; RV endo -4 ms; P < .001). Mental stress depressed the entire electrical restitution curve, with minimal effect on slope. A substantial reduction in minimal ARIs on the restitution curve in LV endo occurred, commensurate with the reduction in ERP (LV endo ARI 195 +/- 31 ms at rest to 182 +/- 32 ms during mental stress; P < .001). Dispersion of repolarization increased sharply at coupling intervals approaching ERP during stress but not at rest. CONCLUSION: Mental stress induces significant electrophysiological changes. The increase in dispersion of repolarization at short coupling intervals may be relevant to observed phenomena of arousal-associated arrhythmia. PMID- 26272523 TI - Novel measure of electrical dyssynchrony predicts response in cardiac resynchronization therapy: Results from the SMART-AV Trial. AB - BACKGROUND: Cardiac resynchronization therapy (CRT) reduces mortality and morbidity in selected heart failure patients. However, not all patients respond to CRT. OBJECTIVE: We hypothesized that a novel measure of electrical dyssynchrony, sum absolute QRST integral (SAI QRST), predicts CRT response independent of QRS duration and morphology. METHODS: We retrospectively analyzed baseline 12-lead electrocardiograms of SmartDelay Determined AV Optimization: A comparison to other AV delay methods used in cardiac resynchronization therapy (SMART-AV) trial study participants (N = 234; mean age 67 years; 163 (70%) men; 140 (60%) ischemic cardiomyopathy; mean left ventricular ejection fraction 25%; mean QRS duration 152 ms; 179 (77%) had left bundle branch block). Baseline pre implant electrocardiograms were digitized, transformed into orthogonal XYZ, and analyzed automatically by customized MATLAB software. SAI QRST was measured as an averaged arithmetic sum of absolute areas under the QRST curve. Patients were followed prospectively 6 months after CRT-defibrillator implantation. Patients with a decrease in left ventricular end-systolic volume >=15 mL after 6 months of CRT were considered responders. The logistic regression model was adjusted for age, sex, bundle branch block morphology, left ventricular ejection fraction, cardiomyopathy type, and QRS duration. RESULTS: Patients with the high mean SAI QRST (third tertile) had 2.5 times greater odds of response than those with the low mean SAI QRST (first tertile: odds ratio [OR] 2.5; 95% confidence interval [CI] 1.3-5.0; P = .010) and 1.9 times greater than the lower 2 tertiles combined (OR 1.9; 95% CI 1.1-3.5; P = .03). Adjustment for renal function (OR 2.33; 95% CI 1.32-4.11; P = .003) and left ventricular lead position in right anterior oblique and left anterior oblique views (OR 1.7; 95% CI 0.9-3.2; P = .087) did not attenuate association of SAI QRST with outcome. CONCLUSION: High SAI QRST independently predicts CRT response in the SMART-AV study. PMID- 26272524 TI - Contact force threshold for permanent lesion formation in atrial fibrillation ablation: A cardiac magnetic resonance-based study to detect ablation gaps. AB - BACKGROUND: Catheter contact force (CF) has a strong correlation with lesion formation during radiofrequency ablation. Delayed-enhancement cardiac magnetic resonance (DE-CMR) provides lesion information in patients with prior atrial fibrillation (AF) ablation. OBJECTIVE: The aim of this study was to determine the CF threshold to create permanent lesions detected by DE-CMR. METHODS: A total of 36 patients referred for AF ablation were included. A CF catheter was used during the ablation procedure, and DE-CMR was performed 3 months after the ablation procedure. Eighteen pulmonary vein (PV) segments were defined, and 3-dimensional (3D) reconstructions of the left atrium (LA) derived from the DE-CMR images were obtained. One observer evaluated the presence of any discontinuity of previous ablation lesions (gap) in the 3D reconstructions of the LA, and another observer (blinded to the gap findings) determined the minimum CF value in each PV segment. RESULTS: The PV segments where a gap was observed had a lower maximal CF value than did the segments without gap in the 3D LA reconstructions (6.7 +/- 4.4 g vs 12.2 +/- 4.7 g; P < .001). In receiver operating characteristic analysis, a CF threshold of >8 g provided 73% sensitivity and 81% specificity in the prediction of a complete PV lesion (positive predictive value [PPV] 84%). A CF threshold of >12 g had a specificity of 94% and increased the PPV to 91% in creating a complete lesion in the LA wall (area under the curve 0.834). CONCLUSION: A CF threshold of >12 g H5H20 predicts a complete lesion with high specificity and PPV when a dragging ablation strategy is used in AF ablation. PMID- 26272522 TI - Incidence of abnormal positron emission tomography in patients with unexplained cardiomyopathy and ventricular arrhythmias: The potential role of occult inflammation in arrhythmogenesis. AB - BACKGROUND: The incidence of myocardial inflammation in patients with unexplained cardiomyopathy referred for ventricular arrhythmias (VAs) is unknown. OBJECTIVE: The purpose of this study was to report fasting positron emission tomographic (PET) scan findings in consecutive patients referred with unexplained cardiomyopathy and VA. METHODS: Fluorine-18 fluoro-2-deoxyglucose (18-FDG) PET/computed tomographic (CT) scans with a >16-hour fasting protocol were prospectively ordered for patients referred for VA and unexplained cardiomyopathy (ejection fraction <55%). Patients with focal myocardial FDG uptake were labeled as arrhythmogenic inflammatory cardiomyopathy (AIC) and classified into 4 groups based on the presence of lymph node uptake (AIC+) and perfusion abnormalities (early vs late stage). RESULTS: Over a 3-year period, 103 PET scans were performed, with 49% (AIC+ 17, AIC 33) exhibiting focal FDG uptake. Mean patient age was 52 +/- 12 years (ejection fraction 36% +/- 16%). Patients with AIC were more likely to have a history of pacemaker (32% vs 6%, P = .002) compared to those with normal PET. When biopsy was performed, histologic diagnosis revealed nongranulomatous inflammation in 6 patients and sarcoidosis in 18 patients. Ninety percent of patients with AIC/AIC+ were prescribed immunosuppressive therapy, and 58% underwent ablation. Correlation between low voltage regions on electroanatomic mapping and FDG uptake was observed in 74%. Magnetic resonance imaging findings matched abnormal PET regions in only 40%. CONCLUSION: Nearly 50% of patients referred with unexplained cardiomyopathy and VA demonstrate ongoing focal myocardial inflammation on FDG PET. These data suggest that a significant proportion of patients labeled "idiopathic" may have occult AIC, which may benefit from early detection and immunosuppressive medical therapy. PMID- 26272526 TI - To the Editor--Diabetes and sudden death: Let's assess the absolute risk increase rather than the proportional risk from sudden cardiac death! PMID- 26272525 TI - Effect of cryoballoon inflation at the right superior pulmonary vein orifice on phrenic nerve location. AB - BACKGROUND: Cryoballoon catheter ablation was developed to simplify ablation for atrial fibrillation (AF). Initial enthusiasm for its widespread use has been dampened by phrenic nerve (PN) injury (PNI). OBJECTIVE: The purpose of this study was to assess the effect of cryoballoon inflation at the right superior pulmonary vein (RSPV) orifice on PN location and to elucidate the potential mechanism of PNI. METHODS: Twenty patients with paroxysmal atrial fibrillation underwent ablation performed with a second-generation 28-mm cryoballoon catheter. Before ablation, the pacing-determined PN course was delineated along the right atrium. PN location and its relation to the RSPV as well as RSPV surface distortions after balloon inflation were established with a NavX mapping system. RESULTS: During RSPV ablation, the inflated balloon surface extended anteriorly 6.3 +/- 1.8 mm outside the RSPV. This narrowed the distance between the PN capture points in the RSPV vs PN location from 11.4 +/- 5.0 mm to 7.5 +/- 5.0 mm (P = .0002) and increased the PN capture area from 1.9 +/- 1.3 cm(2) to 3.2 +/- 1.8 cm(2) (P = .0004). Furthermore, the PN capture points shifted toward the orifice within the RSPV and after balloon inflation were located significantly closer to the orifice in the 3 patients with transient PNI than in those without PNI. CONCLUSION: Cryoballoon inflation at the RSPV orifice alters PV/left atrial surface geometry, reducing the distance between the energy delivery source and the PN and increasing PN area, possibly explaining the mechanism of PNI. PN pacing within the RSPV after balloon inflation may be useful for preventing PNI. PMID- 26272528 TI - A comparison of patients with Q fever fatigue syndrome and patients with chronic fatigue syndrome with a focus on inflammatory markers and possible fatigue perpetuating cognitions and behaviour. AB - OBJECTIVE: Comparison of Q fever fatigue syndrome (QFS) and chronic fatigue syndrome (CFS) patients, with a focus on markers of inflammation and fatigue related cognitive-behavioural variables. METHODS: Data from two independent prospective studies on QFS (n=117) and CFS (n=173), respectively, were pooled and analyzed. RESULTS: QFS patients were less often female, had a higher BMI, and had less often received treatment for depression before the onset of symptoms. After controlling for symptom duration and correcting for differences in diagnostic criteria for QFS and CFS with respect to the level of impairment and the presence of additional symptoms, differences in the proportion of females and BMI remained significant. After correction, QFS patients were also significantly older. In all analyses QFS patients were as fatigued and distressed as CFS patients, but reported less additional symptoms. QFS patients had stronger somatic attributions, and higher levels of physical activity. No differences were found with regard to inflammatory markers and in other fatigue-related cognitive behavioural variables. The relationship between cognitive-behavioural variables and fatigue, previously established in CFS, could not be confirmed in QFS patients with the exception of the negative relationship between physical activity and fatigue. CONCLUSION: Differences and similarities between QFS and CFS patients were found. Although the relationship between perpetuating factors and fatigue previously established in CFS could not be confirmed in QFS patients, the considerable overlap in fatigue-related cognitive-behavioural variables and the relationship found between physical activity and fatigue may suggest that behavioural interventions could reduce fatigue severity in QFS patients. PMID- 26272529 TI - Anterior mediastinal solid tumours in adults: characterisation using dynamic contrast-enhanced MRI, diffusion-weighted MRI, and FDG-PET/CT. AB - AIM: To find significant parameters to characterise anterior mediastinal solid tumours in adults using dynamic contrast-enhanced magnetic resonance imaging (DCE MRI), diffusion-weighted MRI (DWI), and combined 2-[(18)F]-fluoro-2-deoxy-d glucose positron-emission tomography/computed tomography (FDG-PET/CT). MATERIALS AND METHODS: Forty-eight histologically confirmed anterior mediastinal solid tumours in 48 patients (24 men, 24 women; age range 21-83 years, mean 50.7 years) were examined. The parameters analysed were maximal diameter, presence of capsule/septa on T2-weighted images, time-signal intensity curves (TICs), apparent diffusion coefficient (ADC), and maximum standardised uptake value (SUVmax). Also examined was whether any differences between histological types could be seen in these parameters. In a validation study, 42 anterior mediastinal solid tumours in 42 patients were examined consecutively. RESULTS: The washout pattern on TIC was seen only in thymic epithelial tumours (20/32). SUVmax of lymphoma (mean, 17.9), malignant germ cell tumours (14.2), and thymic carcinomas (15.6) were significantly higher than that of thymomas (6.1). The mean maximal diameter of thymic epithelial tumours was significantly smaller than that of lymphomas (p<0.01) and malignant germ cell tumours (p<0.05). The validation study also yielded high accuracy (38/42, 91%) in differentiation among the anterior mediastinal solid tumours. CONCLUSION: The SUVmax, TIC pattern on DCE-MRI, and maximal diameter might be useful to differentiate anterior mediastinal solid tumours in adults. PMID- 26272530 TI - Tumour progression or pseudoprogression? A review of post-treatment radiological appearances of glioblastoma. AB - Glioblastoma (GBM) is a common brain tumour in adults, which, despite multimodality treatment, has a poor median survival. Efficacy of therapy is assessed by clinical examination and magnetic resonance imaging (MRI) features. There is now a recognised subset of treated patients with imaging features that indicate "progressive disease" according to Macdonald's criteria, but subsequently, show stabilisation or resolution without a change in treatment. In these cases of "pseudoprogression", it is believed that non-tumoural causes lead to increased contrast enhancement and conventional MRI is inadequate in distinguishing this from true tumour progression. Incorrect diagnosis is important, as failure to identify pseudoprogression could lead to an inappropriate change of effective therapy. The purpose of this review is to outline the current research into radiological assessment with MRI and molecular imaging of post-treatment GBMs, specifically the differentiation between pseudoprogression and tumour progression. PMID- 26272531 TI - Does Childhood Attention-Deficit/Hyperactivity Disorder (ADHD) Predict Levels of Depressive Symptoms during Emerging Adulthood? AB - Little is known about the development and course of depressive symptoms through emerging adulthood among individuals with a childhood history of attention deficit/hyperactivity disorder (ADHD). The aim of this study was to examine if a history of ADHD in childhood significantly predicted depressive symptoms during emerging adulthood (i.e., ages 18-25 years), including the initial level of depressive symptoms, continued levels of depressive symptoms at each age year, and the rate of change in depressive symptoms over time. 394 participants (205 with ADHD and 189 without ADHD; 348 males and 46 females) drawn from the Pittsburgh ADHD Longitudinal Study (PALS) completed annual self-ratings of depressive symptoms between the ages of 18 and 25 years. Childhood history of ADHD significantly predicted a higher initial level of depressive symptoms at age 18, and higher levels of depressive symptoms at every age year during emerging adulthood. ADHD did not significantly predict the rate of change in depressive symptoms from age 18 to age 25. Childhood history of ADHD remained a significant predictor of initial level of depressive symptoms at age 18 after controlling for comorbid psychiatric diagnoses, but not after controlling for concurrent ADHD symptoms and psychosocial impairment. Participants with childhood histories of ADHD experienced significantly higher levels of depressive symptoms than non-ADHD comparison participants by age 18 and continued to experience higher, although not increasing, levels of depressive symptoms through emerging adulthood. Clinical implications and directions for future research are discussed. PMID- 26272532 TI - Effects of aldose reductase inhibitor on microneurographically assessed peripheral sympathetic nerve activity in rats. AB - Autonomic neuropathy, one of the serious complications of diabetes, decreases quality of life. Aldose reductase inhibitor (ARI) blocks sorbitol production, and results in prevention of damage of nerve fibers. Beneficial effects of ARI have usually been confirmed through nerve conduction velocity tests in motor and sensory nerves. On the other hand, few reports have dealt with the effects of ARI on the small fiber activity such as sympathetic nerve one. In the present study, we administered eparlestat, ARI orally for 3weeks, to streptozotocin-induced diabetic (STZ+ARI) rats, and then recorded peripheral sympathetic nervous signal detected with microneurographic technique. Action potentials (APs) and bursts of APs were detected from the recorded signal, and their rates and incidences (=rates/heart rate) were compared with those in non-diabetic control (normal) and ARI-untreated streptozotocin-induced diabetic (STZ) rats. While streptozotocin and/or epalrestat did not influence burst parameters in all the three groups, AP parameters in the STZ+ARI and normal groups were higher than those in the STZ group. However, response of AP parameters to the intravenous glucose administration (IVGA) was not large in the STZ+ARI group, similar to that of the STZ group and different from that of the normal group in which AP parameters increased after IVGA. The results suggest that epalrestat may prevent sympathetic nerve activity (SNA) from reduction under hyperglycemic and insulin-depleted conditions, that enhancement of SNA was not induced after IVGA under that condition, and that AP parameters might be useful to assess the degree of neuropathy. PMID- 26272533 TI - Predictive markers, including total lesion glycolysis, for the response of lymph node(s) metastasis from head and neck squamous cell carcinoma treated by chemoradiotherapy. AB - BACKGROUND: Chemoradiotherapy (CRT) is used to treat cervical lymph node(s) metastatic head and neck cancer patients. Evaluation and treatment of lymph node(s) after CRT is important to improve the prognosis. METHODS: Prior to CRT, we determined the TNM stage by visual and imaging examinations. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated from the results of fluorodeoxyglucose-positron emission tomography (FDG-PET). After CRT, the patients were divided in two groups-complete response (CR) and non-CR-and their responses were compared with the clinical characteristics. RESULTS: T4, N2b, N2c and TLG2.5 >= 18.8 were statistically significant predictive indices before CRT. The odds ratio, 95 % confidence interval and p value were, respectively-T4: 2.73, 1.15-6.51, 0.0230; N2b: 6.96, 1.50-32.3, 0.0132; N2c: 11.80, 2.37-58.50, 0.00258; and TLG2.5 >= 18.8: 6.25, 2.17-18.00, 0.000672. CONCLUSIONS: TLG was found to be a good predictive factor for metastatic lymph node(s) prior to CRT treatment. After CRT treatment, FDG-PET was found to be highly specific and useful for negative screening. PMID- 26272534 TI - The effects of intra-dorsal hippocampus infusion of pregnenolone sulfate on memory function and hippocampal BDNF mRNA expression of biliary cirrhosis-induced memory impairment in rats. AB - Learning and memory impairment is one of the most challenging complications of cirrhosis and present treatments are unsatisfactory. The exact mechanism of cirrhosis cognitive dysfunction is unknown. Pregnenolone sulfate (PREGS) is an excitatory neurosteroid that acts as a N-methyl-D-aspartate (NMDA) receptor agonist and GABAA receptor antagonist. In this study we evaluated the effect of intra CA1 infusion of PREGS on cirrhotic rats' memory function using the Y-maze test. Hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression was also evaluated. Three weeks after bile duct ligation (BDL) surgery, rats were under stereotaxic surgery for insertion of two guide cannulas in the CA1 region of the hippocampus. After 1-week of recovery, PREGS was administered through CA1 cannulas in cirrhotic rats, while control or sham groups received vehicle. For evaluation of NMDA receptor role in memory-enhancing effects of PREGS, DL-2-Amino 5-phosphonopentanoic acid (AP5) which is a potent and competitive antagonist of NMDA receptor, co-administered with PREGS and for assessment of hippocampal BDNF mRNA expression, quantitative Real-time reverse transcriptase-PCR (RT-PCR) was used. Results showed that 28 days after BDL, cirrhotic animals' memory significantly decreased in comparison with control and sham groups, while PREGS infusion could restore memory impairment (P<0.05). PREGS effects on memory of cirrhotic rats were antagonized by DAP5. RT-PCR findings have shown that hippocampal relative BDNF mRNA expression was up-regulated in PREGS-treated groups in comparison with the BDL group (P<0.001). Our findings suggest that PREGS has a memory-enhancing effect in cirrhosis memory deficit in acute therapy and this effect may be through NMDA (glutamate) receptor involvement and BDNF mRNA expression. PMID- 26272536 TI - Effects of environmental enrichment on behavioral deficits and alterations in hippocampal BDNF induced by prenatal exposure to morphine in juvenile rats. AB - Prenatal morphine exposure throughout pregnancy can induce a series of neurobehavioral and neurochemical disturbances by affecting central nervous system development. This study was designed to investigate the effects of an enriched environment on behavioral deficits and changes in hippocampal brain derived neurotrophic factor (BDNF) levels induced by prenatal morphine in rats. On pregnancy days 11-18, female Wistar rats were randomly injected twice daily with saline or morphine. Offspring were weaned on postnatal day (PND) 21. They were subjected to a standard rearing environment or an enriched environment on PNDs 22-50. On PNDs 51-57, the behavioral responses including anxiety and depression-like behaviors, and passive avoidance memory as well as hippocampal BDNF levels were investigated. The light/dark (L/D) box and elevated plus maze (EPM) were used for the study of anxiety, forced swimming test (FST) was used to assess depression-like behavior and passive avoidance task was used to evaluate learning and memory. Prenatal morphine exposure caused a reduction in time spent in the EPM open arms and a reduction in time spent in the lit side of the L/D box. It also decreased step-through latency and increased time spent in the dark side of passive avoidance task. Prenatal morphine exposure also reduced immobility time and increased swimming time in FST. Postnatal rearing in an enriched environment counteracted with behavioral deficits in the EPM and passive avoidance task, but not in the L/D box. This suggests that exposure to an enriched environment during adolescence period alters anxiety profile in a task specific manner. Prenatal morphine exposure reduced hippocampal BDNF levels, but enriched environment significantly increased BDNF levels in both saline- and morphine-exposed groups. Our results demonstrate that exposure to an enriched environment alleviates behavioral deficits induced by prenatal morphine exposure and up-regulates the decreased levels of BDNF. BDNF may contribute to the beneficial effects of an enriched environment on prenatal morphine-exposed to rats. PMID- 26272537 TI - Can Listeners Hear Who Is Singing? The Role of Familiarity. AB - OBJECTIVE/HYPOTHESIS: This study sought to determine whether familiarity with voices increases discrimination of voices across pitch intervals. STUDY DESIGN: This is a between-group design. METHODS: This study used a forced-choice paradigm where listeners heard two different singers (singer 1 and singer 2) producing /alpha/ at the identical pitch and an unknown singer (either singer 1 or singer 2) producing /alpha/ at a different pitch. Listeners had to identify which singer was the unknown singer. Two baritones and two tenors were recorded producing /alpha/ at the pitches C3, E3, G3, B3, D4, and F4. Two sopranos and two mezzo sopranos were recorded producing /alpha/ at the pitches C4, E4, G4, B4, D5, and F5. For each group of stimuli, male and female, all possible pairs of singers were constructed for the lowest pitch (C2 or C3, respectively) and for the highest pitch (F4 or F5, respectively). The unknown singer was varied across the remaining pitches. Participants in group 1 completed a training session where they were familiarized with the voices being tested. Participants in group 2 did not. RESULTS: Training did not significantly improve the ability to discriminate voices when the voices being compared were of the same voice category. However, training did significantly improve the ability to discriminate voices when the voices being compared were of different voice categories even when training lasted as little as 5 minutes. CONCLUSIONS: Small amount of exposure to human voices results in voice category formation but does not result in the formation of models of individual voices. PMID- 26272535 TI - The placebo effect: From concepts to genes. AB - Despite its initial treatment as a nuisance variable, the placebo effect is now recognized as a powerful determinant of health across many different diseases and encounters. This is in light of some remarkable findings ranging from demonstrations that the placebo effect significantly modulates the response to active treatments in conditions such as pain, anxiety, Parkinson's disease, and some surgical procedures. Here, we review pioneering studies and recent advances in behavioral, neurobiological, and genetic influences on the placebo effect. Consistent with recent conceptualizations, the placebo effect is presented as the product of a general expectancy learning mechanism in which verbal, conditioned, and social cues are centrally integrated to change behaviors and outcomes. Examples of the integration of verbal and conditioned cues, such as instructed reversal of placebo effects are also incorporated into this model. We discuss neuroimaging studies that have identified key brain regions and modulatory mechanisms underlying placebo effects using well-established behavioral paradigms. Finally, we present a synthesis of recent genetics studies on the placebo effect, highlighting a promising link between genetic variants in the dopamine, opioid, serotonin, and endocannabinoid pathways and placebo responsiveness. Greater understanding of the behavioral, neurobiological, and genetic influences on the placebo effect is critical for evaluating medical interventions and may allow health professionals to tailor and personalize interventions in order to maximize treatment outcomes in clinical settings. PMID- 26272538 TI - Laryngeal Side Effects of Tyrosine Kinase Inhibitors. AB - OBJECTIVES: Tyrosine kinase inhibitors (TKIs) are common targeted drugs, used in the treatment of hematological and solid malignancies. These drugs present a multitude of potential adverse effects. Laryngeal manifestations, including laryngeal edema, secondary to TKIs treatment have not been well studied, despite their potential lethality. METHODS: This cross-sectional study included adult patients (>18 years) treated with TKIs who were followed in a secondary medical center and underwent a voluntary otolaryngological examination, which included laryngeal fiber-optic laryngoscopy (FOL). FOL was independently performed by two senior otolaryngologists, and results were recorded and evaluated by two grading systems, to assess the degree of laryngeal edema. In addition, medical files were reviewed, and data collected included past medical history, signs and symptoms, physical examination, laboratory results, treatment type, and duration. RESULTS: Sixteen patients, aged 68.2 +/- 13.6 years, were examined during October 2014 to December 2014. Of them, three (19%) were males. Eleven (68%) patients presented with varying degrees of laryngeal edema. A significant correlation was found between gastroesophageal reflux symptoms and laryngeal edema (P = 0.02). TKI treatment was stopped in one patient, because of symptomatic laryngeal edema, which completely resolved within 2 weeks. CONCLUSIONS: Laryngeal edema was common in our study group. This edema was most often not life threatening. Yet, because of the potential severity of this side effect, we propose a routine FOL examination of patients before commencing TKI treatment and a reevaluation performed during treatment. PMID- 26272539 TI - Sex Differences in Depression: Does Inflammation Play a Role? AB - Women become depressed more frequently than men, a consistent pattern across cultures. Inflammation plays a key role in initiating depression among a subset of individuals, and depression also has inflammatory consequences. Notably, women experience higher levels of inflammation and greater autoimmune disease risk compared to men. In the current review, we explore the bidirectional relationship between inflammation and depression and describe how this link may be particularly relevant for women. Compared to men, women may be more vulnerable to inflammation-induced mood and behavior changes. For example, transient elevations in inflammation prompt greater feelings of loneliness and social disconnection for women than for men, which can contribute to the onset of depression. Women also appear to be disproportionately affected by several factors that elevate inflammation, including prior depression, somatic symptomatology, interpersonal stressors, childhood adversity, obesity, and physical inactivity. Relationship distress and obesity, both of which elevate depression risk, are also more strongly tied to inflammation for women than for men. Taken together, these findings suggest that women's susceptibility to inflammation and its mood effects may contribute to sex differences in depression. Depression continues to be a leading cause of disability worldwide, with women experiencing greater risk than men. Due to the depression-inflammation connection, these patterns may promote additional health risks for women. Considering the impact of inflammation on women's mental health may foster a better understanding of sex differences in depression, as well as the selection of effective depression treatments. PMID- 26272541 TI - Psychometric integrity of the Chinese Happiness Inventory among retired older people in Taiwan. AB - AIM: Happiness is an important indicator of mental and physical health. It has been emphasized as one kind of well-being, and its definition varies from culture to culture. The main objective of the present study was to examine the psychometric integrity and dimensions of the Chinese Happiness Inventory (CHI) in relation to scores on Ryff's Psychological Well-Being Scale among retired older people in Taiwan. METHODS: A cross-sectional study was carried out at social service centers in Taipei, Taiwan. Retired adults gave informed consent from September to November 2010, and completed a package of structured questionnaires measuring happiness and psychological well-being. Internal consistency, the factor structure of the CHI and criterion validity were assessed. RESULTS: Results from an exploratory factor analysis showed a three-factor solution for the CHI. These factors were named Positive Affect, Life Satisfaction and Interpersonal Relationships. Internal consistency coefficients were 0.95 (Positive Affect), 0.91 (Life Satisfaction), 0.85 (Interpersonal Relationships) and 0.97 (total scale). The results of a canonical correlation analysis showed the presence of a strong relationship between CHI and Ryff's Psychological Well Being Scale (r = 0.69), and that two canonical variates could be derived from the relationship between them. CONCLUSIONS: The results show that the CHI is a three dimensional scale with high reliability and validity. The construct of happiness emphasizes relationships in relation to others and environment rather than autonomy in this sample. Although the components of happiness might be similar for Positive Affect and Life Satisfaction, their weights for Interpersonal Relationships should be considered when measuring happiness in different cultures. Geriatr Gerontol Int 2016; 16: 865-872. PMID- 26272540 TI - Neuroimaging the Menstrual Cycle and Premenstrual Dysphoric Disorder. AB - Knowledge of gonadal hormone-related influences on human brain anatomy, function, and chemistry is scarce. The present review scrutinized organizational and functional neuroimaging correlates of the menstrual cycle and premenstrual dysphoric disorder (PMDD). Supportive evidence of cyclic short-term structural and functional brain plasticity in response to gonadal hormonal modulation is provided. The paucity of studies, sparsity and discordance of findings, and weaknesses in study design at present hinder the drawing of firm conclusions. Ideal study designs should comprise high-resolution multimodal neuroimaging (e.g., MRI, DTI, rs-fMRI, fMRI, PET), hormones, genetic, and behavioral longitudinal assessments of healthy women and PMDD patients at critical time points of the menstrual cycle phase (i.e., early follicular phase, late follicular phase, mid-luteal phase) in a counter-balanced setup. Studies integrating large-scale brain network structural, functional, and molecular neuroimaging, as well as treatment data, will deepen the understanding of neural state, disorder, and treatment markers. PMID- 26272542 TI - Overview: Core technical elements for early product development, evaluation, and control of human cell-based products. AB - Essential scientific elements for early product development, evaluation, and control of human cell-based products for cell therapy are addressed in a comprehensive and unifying way. Among them, donor issues (autologous and allogeneic), testing of raw materials, cell banking and cell substrate characterization, testing for adventitious agents (viral safety), and product sterility are very much related to each other. A significant amount of expertise exists in these areas both for traditional biologicals as well as for biotechnology products. Thus, core principles/concepts as well as the testing methodologies are already well defined. Other critical technical elements that are essential but need further discussion in terms of relevant regulatory requirements and testing methods are touched upon very briefly and followed by a detailed discussion (elsewhere). PMID- 26272543 TI - Scanning EM of non-heavy metal stained biosamples: Large-field of view, high contrast and highly efficient immunolabeling. AB - Scanning electron microscopy (SEM) is increasing its application in life sciences for electron density measurements of ultrathin sections. These are traditionally analyzed with transmission electron microscopy (TEM); by most labs, SEM analysis still is associated with surface imaging only. Here we report several advantages of SEM for thin sections over TEM, both for structural inspection, as well as analyzing immuno-targeted labels such as quantum dots (QDs) and gold, where we find that QD-labeling is ten times more efficient than gold-labeling. Furthermore, we find that omitting post-staining with uranyl and lead leads to QDs readily detectable over the ultrastructure, but under these conditions ultrastructural contrast was even almost invisible in TEM examination. Importantly, imaging in SEM with STEM detection leads to both outstanding QDs and ultrastructural contrast. STEM imaging is superior over back-scattered electron imaging of these non-contrasted samples, whereas secondary electron detection cannot be used at all. We conclude that examination of ultrathin sections by SEM, which may be immunolabeled with QDs, will allow rapid and straightforward analysis of large fields with more efficient labeling than can be achieved with immunogold. The large fields of view routinely achieved with SEM, but not with TEM, allows straightforward raw data sharing using virtual microscopy, also known as nanotomy when this concerns EM data in the life sciences. PMID- 26272544 TI - Role of c-Jun N-terminal kinase in the osteogenic and adipogenic differentiation of human adipose-derived mesenchymal stem cells. AB - Although previous studies have characterized the osteogenic potential of adipose derived mesenchymal stem cells (AMSCs) in vitro and in vivo, the molecular mechanism involved remains to be fully determined. Previously, we demonstrated that the ERK pathway plays an important role in osteogenesis and regulation of the balance between osteogenesis and adipogenesis. Here, we explored the possible role of JNKs in osteogenesis and adipogenesis of AMSCs. JNK activation in osteo induced AMSCs was initiated at 15 min, peaked at 30 min, and declined from 45 min to basal levels. Inhibition of the JNK signaling pathway using SP600125 blocked osteogenic differentiation in a dose-dependent manner, which was revealed by an ALP activity assay, extracellular calcium deposition detection, and expression of osteogenesis-relative genes (Runx2, ALP, and OCN) via RT-PCR and real-time PCR. However, blockage of JNK did not induce a switch between osteogenesis and adipogenesis of AMSCs in the presence of dexamethasone, which is different from that of blockage of ERK. Significantly, the blockage of JNK activation in adipo induced AMSCs by SP600125 stimulated adipogenic differentiation, which was confirmed by Oil Red O staining to detect intracellular lipid droplets, and RT PCR and real-time PCR analysis for expression of adipogenesis-relative genes (PPARgamma2 and aP2). This study suggested a potential function of the JNK pathway in committing osteogenic and adipogenic differentiation of AMSCs in vitro. However, blockage of the JNK pathway is not sufficient to induce a switch from osteogenesis to adipogenesis of AMSCs. PMID- 26272545 TI - The effect of health insurance on workers' compensation filing: Evidence from the affordable care act's age-based threshold for dependent coverage. AB - This paper identifies the effect of health insurance on workers' compensation (WC) filing for young adults by implementing a regression discontinuity design using WC medical claims data from Texas. The results suggest health insurance factors into the decision to have WC pay for discretionary care. The implied instrumental variables estimates suggest a ten-percentage-point decrease in health insurance coverage increases WC bills by 15.3 percent. Despite the large impact of health insurance on the number of WC bills, the additional cost to WC at age 26 appears to be small as most of the increase comes from small bills. PMID- 26272546 TI - Aortic Dissection Presenting as "Hysteria". AB - BACKGROUND: Patients with medical conditions may present with psychiatric symptoms, which may lead to worse physical health care. Here we present the case of a patient with acute aortic dissection masked by psychiatric symptoms after a stressful event. CASE REPORT: A 29-year-old female medical student presented to the Emergency Department (ED) complaining about the feeling of "hysteria" after an argument with her boyfriend earlier the same day. She did not report other symptoms or pain. Careful physical examination, initially impeded by the patient's agitation, revealed pulseless extremities. Blood gas analysis showed metabolic acidosis. Transthoracic echocardiography and computed tomography ultimately led to the correct diagnosis: Stanford Type-A aortic dissection. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Medical conditions requiring acute diagnostic work-up and therapy may present with psychiatric symptoms. Increased awareness and the use of standardized operating procedures in the ED may prevent fatal misdiagnoses in these patients. PMID- 26272547 TI - Chinese Medicine Amygdalin and beta-Glucosidase Combined with Antibody Enzymatic Prodrug System As A Feasible Antitumor Therapy. AB - Amarogentin is an efficacious Chinese herbal medicine and a component of the bitter apricot kernel. It is commonly used as an expectorant and supplementary anti-cancer drug. beta-Glucosidase is an enzyme that hydrolyzes the glycosidic bond between aryl and saccharide groups to release glucose. Upon their interaction, beta-glucosidase catalyzes amarogentin to produce considerable amounts of hydrocyanic acid, which inhibits cytochrome C oxidase, the terminal enzyme in the mitochondrial respiration chain, and suspends adenosine triphosphate synthesis, resulting in cell death. Hydrocyanic acid is a cell-cycle stage-nonspecific agent that kills cancer cells. Thus, beta-glucosidase can be coupled with a tumor-specific monoclonal antibody. beta-Glucosidase can combine with cancer-cell-surface antigens and specifically convert amarogentin to an active drug that acts on cancer cells and the surrounding antibodies to achieve a killing effect. beta-Glucosidase is injected intravenously and recognizes cancer cell-surface antigens with the help of an antibody. The prodrug amarogentin is infused after beta-glucosidase has reached the target position. Coupling of cell membrane peptides with beta-glucosidase allows the enzyme to penetrate capillary endothelial cells and clear extracellular deep solid tumors to kill the cells therein. The Chinese medicine amarogentin and beta-glucosidase will become an important treatment for various tumors when an appropriate monoclonal antibody is developed. PMID- 26272549 TI - Panax ginseng inhibits intestinal absorption of toxic Aconitum carmichaeli alkaloids in Vitro. AB - OBJECTIVE: To evaluate the rationality and compatibility of Shenfu Formula (, SFF), a typical Chinese medicine (CM) comprised of Panax ginseng and Aconitum carmichaeli. METHODS: Caco-2 cells were used to study the permeability of Aconitum carmichaeli marker compounds when the CM preparation was combined with Panax ginseng. P-glycoprotein (P-gp) activity and protein as well as multidrug resistance 1 (MDR1) mRNA were analyzed with rhodamine123 efflflux, western blot and real time quantitative polymerase chain reaction. RESULTS: Aconitine (AC), mesaconitine (MA), hypaconitine (HA) and fifive other active alkaloids in Aconitum carmichaeli were selected as marker compounds. Panax ginseng inhibited intestinal absorption of highly toxic AC, MA and HA from Aconitum carmichaeli in Caco-2 cells. P-gp and breast cancer resistance protein (BCRP) were observed to be involved in AC, MA and HA efflflux. Panax ginseng induced P-gp activity in Caco-2 cells via increased MDR1/P-gp expression. Thus, Panax ginseng facilitated P-gp-mediated efflflux of toxic Aconitum carmichaeli alkaloids and restricted their intestinal absorption without inflfluencing other active components. CONCLUSION: Future studies to elucidate mechanism of reduced toxicity of Aconitum carmichaeli when combined with Panax ginseng will guide future formula optimization. PMID- 26272548 TI - Clinical study of pai-neng-da capsule in the treatment of chronic aplastic anemia. AB - OBJECTIVE: To evaluate the efficacy and safety of Pai-Neng-Da Capsule (panaxadiol saponins component, PND), a new Chinese patent medicine, on patients with chronic aplastic anemia (CAA) and to explore the optimal therapeutic regimen for CAA. METHOD: A total of 36 patients with CAA were enrolled and divided into three groups: the AP group (20 cases, andriol 120 mg/day + PND 240 mg/day), the ACP group (13 cases, andriol 120 mg/day + cyclosporine 3-6 mg kd(-1) day(-1) + PND 240 mg/day), and the PND group (3 cases, PND 240 mg/day). All patients were treated and followed up for 6 months. Peripheral blood counts, renal and hepatic function and Chinese medical (CM) symptoms of patients were assessed and all indices were gathered at the beginning and end of the study. RESULT: In the AP group, no significant hematologic difference was observed at the end of 6-month treatment comparing with the beginning. In the ACP group, the blood counts were maintained at the same level after the 6-month treatment. In the PND group, trilineage hematologic improvement was displayed at the end of 6-month treatment comparing with the beginning. No significant difference was showed in renal and hepatic function in all patients. All patients' clinical symptom improved according to CM symptom score. The effective rates were 95%, 73% and 100%, respectively. CONCLUSION: PND improved the efficacy and decreased side effects by cutting down the dosage of andriol, and it could also improve patients' clinical symptom and quality of life. PND were effective and safe in the treatment of CAA, it could be used alone or in combination with pharmacological agents such as andriol and cyclosporine. PMID- 26272550 TI - In Vitro Angiogenesis Effect of Xuefu Zhuyu Decoction () and Vascular Endothelial Growth Factor: A Comparison Study. AB - OBJECTIVE: To compare the angiogenesis behaviors of vascular endothelial growth factor (VEGF) and Chinese medicine Xuefu Zhuyu Decoction (, XZD) treatments. METHODS: Human microvascular endothelial cells (HMEC-1) were treated with various concentrations of either XZD-containing serum (XZD-CS) or VEGF for 24, 48, and 72 h, respectively. Cell viability, proliferation, migration, adhesion, and in vitro tube formation assays were used to assess their angiogenic effects. RESULTS: VEGF promoted all cellular phases involved in angiogenesis including cell viability, proliferation, migration, adhesion, and tube formation (<0.05 or <0.01). Unlike the continuous promotion effects of VEGF at the above stages, XZD inhibited cell viability and proliferation (<0.05 or <0.01) and only promoted tube formation in the early phase of angiogenesis (<0.01). CONCLUSIONS: These two medications promote different angiogenesis behaviors, which might be an important reason for their distinct therapeutic profile in clinical usage. PMID- 26272552 TI - UV-B-Induced CPD Photolyase Gene Expression is Regulated by UVR8-Dependent and Independent Pathways in Arabidopsis. AB - Plants have evolved various mechanisms that protect against the harmful effects of UV-B radiation (280-315 nm) on growth and development. Cyclobutane pyrimidine dimer (CPD) photolyase, the repair enzyme for UV-B-induced CPDs, is essential for protecting cells from UV-B radiation. Expression of the CPD photolyase gene (PHR) is controlled by light with various wavelengths including UV-B, but the mechanisms of this regulation remain poorly understood. In this study, we investigated the regulation of PHR expression by light with various wavelengths, in particular low-fluence UV-B radiation (280 nm, 0.2 umol m(-2) s(-1)), in Arabidopsis thaliana seedlings grown under light-dark cycles for 7 d and then adapted to the dark for 3 d. Low-fluence UV-B radiation induced CPDs but not reactive oxygen species. AtPHR expression was effectively induced by UV-B, UV-A (375 nm) and blue light. Expression induced by UV-A and blue light was predominantly regulated by the cryptochrome-dependent pathway, whereas phytochromes A and B played a minor but noticeable role. Expression induced by UV B was predominantly regulated by the UVR8-dependent pathway. AtPHR expression was also mediated by a UVR8-independent pathway, which is correlated with CPD accumulation induced by UV-B radiation. These results indicate that Arabidopsis has evolved diverse mechanisms to regulate CPD photolyase expression by multiple photoreceptor signaling pathways, including UVR8-dependent and -independent pathways, as protection against harmful effects of UV-B radiation. PMID- 26272551 TI - Expression of Cyanobacterial Acyl-ACP Reductase Elevates the Triacylglycerol Level in the Red Alga Cyanidioschyzon merolae. AB - Nitrogen starvation is known to induce the accumulation of triacylglycerol (TAG) in many microalgae, and potential use of microalgae as a source of biofuel has been explored. However, nitrogen starvation also stops cellular growth. The expression of cyanobacterial acyl-acyl carrier protein (ACP) reductase in the unicellular red alga Cyanidioschyzon merolae chloroplasts resulted in an accumulation of TAG, which led to an increase in the number and size of lipid droplets while maintaining cellular growth. Transcriptome and metabolome analyses showed that the expression of acyl-ACP reductase altered the activities of several metabolic pathways. The activities of enzymes involved in fatty acid synthesis in chloroplasts, such as acetyl-CoA carboxylase and pyruvate dehydrogenase, were up-regulated, while pyruvate decarboxylation in mitochondria and the subsequent consumption of acetyl-CoA by the tricarboxylic acid (TCA) cycle were down-regulated. Aldehyde dehydrogenase, which oxidizes fatty aldehydes to fatty acids, was also up-regulated in the acyl-ACP reductase expresser. This activation was required for the lipid droplet accumulation and metabolic changes observed in the acyl-ACP reductase expresser. Nitrogen starvation also resulted in lipid droplet accumulation in C. merolae, while cell growth ceased as in the case of other algal species. The metabolic changes that occur upon the expression of acyl-ACP reductase are quite different from those caused by nitrogen starvation. Therefore, there should be a method for further increasing the storage lipid level while still maintaining cell growth that is different from the metabolic response to nitrogen starvation. PMID- 26272553 TI - Convoluted Plasma Membrane Domains in the Green Alga Chara are Depleted of Microtubules and Actin Filaments. AB - Charasomes are convoluted plasma membrane domains in the green alga Chara australis. They harbor H(+)-ATPases involved in acidification of the medium, which facilitates carbon uptake required for photosynthesis. In this study we investigated the distribution of cortical microtubules and cortical actin filaments in relation to the distribution of charasomes. We found that microtubules and actin filaments were largely lacking beneath the charasomes, suggesting the absence of nucleating and/or anchoring complexes or an inhibitory effect on polymerization. We also investigated the influence of cytoskeleton inhibitors on the light-dependent growth and the darkness-induced degradation of charasomes. Inhibition of cytoplasmic streaming by cytochalasin D significantly inhibited charasome growth and delayed charasome degradation, whereas depolymerization of microtubules by oryzalin or stabilization of microtubules by paclitaxel had no effect. Our data indicate that the membrane at the cytoplasmic surface of charasomes has different properties in comparison with the smooth plasma membrane. We show further that the actin cytoskeleton is necessary for charasome growth and facilitates charasome degradation presumably via trafficking of secretory and endocytic vesicles, respectively. However, microtubules are required neither for charasome growth nor for charasome degradation. PMID- 26272554 TI - Mapping the pulmonary environment of animals protected from virulent H1N1 influenza infection using the TLR-2 agonist Pam2Cys. AB - We have previously shown that intranasal administration of the Toll-like receptor 2 agonist, S-(2,3-bis(palmitoyloxy)propyl) cysteine (Pam2Cys), provides immediate and antigen independent protection against challenge with influenza virus. Here we characterize the cellular pulmonary environments of mice which had either been treated with Pam2Cys or placebo and then challenged with influenza virus. We show that Pam2Cys treatment results in the influx of innate immune cells into the lungs and that depletion of phagocytic cells from this influx using clodronate loaded liposomes caused a reduction in the number of interstitial macrophages and monocytes. This resulted in abolition of the protective effect indicating the importance of this cellular subset in Pam2Cys-mediated protection. PMID- 26272556 TI - Draft Genome Sequence of "Candidatus Hepatoplasma crinochetorum" Ps, a Bacterial Symbiont in the Hepatopancreas of the Terrestrial Isopod Porcellio scaber. AB - "Candidatus Hepatoplasma crinochetorum" Ps is an extracellular symbiont residing in the hepatopancreas of the terrestrial isopod Porcellio scaber. Its genome is highly similar to that of the close relative "Ca. Hepatoplasma crinochetorum" Av from Armadillidium vulgare. However, instead of a clustered regularly interspaced short palindromic repeat (CRISPR)-Cas system, it encodes a type I restriction modification system. PMID- 26272555 TI - IL-7 induces clathrin-mediated endocytosis of CD127 and subsequent degradation by the proteasome in primary human CD8 T cells. AB - Interleukin-7 (IL-7), a key immunoregulatory cytokine, plays an essential role in peripheral T-cell homeostasis and function. Signaling via the IL-7 receptor is tightly regulated and we and others have shown IL-7 provides negative feedback on its own signaling by downregulating expression of the IL-7 receptor alpha-chain (CD127) through both suppression of CD127 gene transcription and by internalization of existing CD127 proteins from the cell membrane. We show here for the first time in primary human CD8 T cells that upon stimulation with IL-7, CD127 is internalized through clathrin-coated pits, a process dependent on both lipid-raft formation and the activity of dynamin. As visualized by confocal microscopy, CD127 shows increased co-localization with clathrin within 5 min of IL-7 stimulation and within 15-30 min is seen in multiple intracellular punctae co-localizing with the early endosomal marker EEA1. By 2 h after addition of IL 7, CD127 staining associates with the late endosomal marker RAB7 and with the proteasomal 20S subunit. By inducing receptor internalization and translocation from early endosomes to the proteasome, IL-7 directly influences its receptor density on the cell surface and thus regulates the intensity of its own signaling cascades. Given the important role IL-7 plays in T-cell development, homeostasis and function, deciphering how expression of its receptor is controlled on the cell surface is essential in understanding how T-cell activity can be regulated in different microenvironments and in response to different pathogens. PMID- 26272557 TI - Complete Genome Sequence of Phytopathogenic Pectobacterium atrosepticum Bacteriophage Peat1. AB - Pectobacterium atrosepticum is a common phytopathogen causing significant economic losses worldwide. To develop a biocontrol strategy for this blackleg pathogen of solanaceous plants, P. atrosepticum bacteriophage Peat1 was isolated and its genome completely sequenced. Interestingly, morphological and sequence analyses of the 45,633-bp genome revealed that phage Peat1 is a member of the family Podoviridae and most closely resembles the Klebsiella pneumoniae bacteriophage KP34. This is the first published complete genome sequence of a phytopathogenic P. atrosepticum bacteriophage, and details provide important information for the development of biocontrol by advancing our understanding of phage-phytopathogen interactions. PMID- 26272558 TI - Complete Genome Sequence of Middle East Respiratory Syndrome Coronavirus KOR/KNIH/002_05_2015, Isolated in South Korea. AB - The full genome sequence of a Middle East respiratory syndrome coronavirus (MERS CoV) was identified from cultured and isolated in Vero cells. The viral genome sequence has high similarity to 53 human MERS-CoVs, ranging from 99.5% to 99.8% at the nucleotide level. PMID- 26272559 TI - Draft Genome Sequences of Ralstonia solanacearum Race 3 Biovar 2 Strains with Different Temperature Adaptations. AB - Ralstonia solanacearum race 3 biovar 2 (R3bv2) causes brown rot of potato in countries with temperate climates. Here, we report two draft genome sequences of R. solanacearum R3bv2 NCPPB909 and CFIA906 with different temperature adaptations. Analysis of these genome sequences will provide detailed insight on virulence, functionality, and plant/pest interactions of this widely distributed and regulated pathogen. PMID- 26272560 TI - Complete Genome Sequence of Middle East Respiratory Syndrome Coronavirus (MERS CoV) from the First Imported MERS-CoV Case in China. AB - On 26 May 2015, an imported Middle East respiratory syndrome coronavirus (MERS CoV) was identified in Guangdong Province, China, and found to be closely related to the MERS-CoV strain prevalent in South Korea. The full genome of the ChinaGD01 strain was sequenced and analyzed to investigate the epidemiology and evolution of MERS-CoV circulating in South Korea and China. PMID- 26272561 TI - Draft Genome Sequence of Bacillus ginsengihumi Strain M2.11 with Phytase Activity. AB - This paper announces the genome sequence of Bacillus ginsengihumi strain M2.11, which has been characterized as a strain which produces the enzyme with the ability to degrade phytase. The genome of the strain M2.11 is 3.7 Mb and harbors 3,082 coding sequences. PMID- 26272562 TI - Complete Genome Sequence of Bacillus amyloliquefaciens Strain Co1-6, a Plant Growth-Promoting Rhizobacterium of Calendula officinalis. AB - The genome sequence of Bacillus amyloliquefaciens strain Co1-6, a plant growth promoting rhizobacterium (PGPR) with broad-spectrum antagonistic activity against plant-pathogenic fungi, bacteria, and nematodes, consists of a single 3.9-Mb circular chromosome. The genome reveals genes putatively responsible for its promising biocontrol and PGP properties. PMID- 26272563 TI - Genome Sequences of Three Oenococcus oeni Strains Isolated from Maipo Valley, Chile. AB - Oenococcus oeni is part of the microbial terroir involved in wine production. Here, we present three genome sequences of O. oeni strains isolated from spontaneous malolactic fermentation of cultivar Cabernet Sauvignon Maipo Valley, Chile. PMID- 26272564 TI - Draft Genome Sequence of Multidrug-Resistant Enterococcus faecium Clinical Isolate VRE3, with a Sequence Type 16 Pattern and Novel Structural Arrangement of Tn1546. AB - Multidrug-resistant Enterococcus faecium has emerged as a nosocomial pathogen that may infect the body at various sites, including the gastrointestinal tract, and has serious implications in human health and disease. Here, we present the draft genome sequence of clinical strain VRE3, which exhibited a sequence type 16 (ST16) pattern and carried truncated Tn1546, a mobile genetic element encoding a high level of vancomycin resistance. PMID- 26272565 TI - Draft Genome Sequence of the Picocyanobacterium Synechococcus sp. Strain GFB01, Isolated from a Freshwater Lagoon in the Brazilian Amazon. AB - We present the draft genome of the cyanobacterium strain Synechococcus sp. GFB01, the first genome sequencing of this genus isolated from South America. This draft genome consists of 125 contigs with a total size of 2,339,812 bp. Automatic annotation identified several genes involved with heavy metal resistance and natural transformation. PMID- 26272566 TI - Complete Genome Sequence of the Porcine Epidemic Diarrhea Virus Variant Tottori2/JPN/2014. AB - Porcine epidemic diarrhea virus (PEDV) is a cause of diarrhea outbreaks at swine farms, causing vomiting, severe diarrhea, and mortality in piglets. We sequenced and analyzed the complete genome of recently isolated strains. Tottori2/JPN/2014, one of the sequenced PEDV strains, had a unique large deletion in the S gene. PMID- 26272567 TI - Complete Genome Sequences of Low-Passage Virulent and High-Passage Avirulent Variants of Pathogenic Leptospira interrogans Serovar Manilae Strain UP-MMC-NIID, Originally Isolated from a Patient with Severe Leptospirosis, Determined Using PacBio Single-Molecule Real-Time Technology. AB - Here, we report the complete genome sequences of low-passage virulent and high passage avirulent variants of pathogenic Leptospira interrogans serovar Manilae strain UP-MMC-NIID, a major causative agent of leptospirosis. While there were no major differences between the genome sequences, the levels of base modifications were higher in the avirulent variant. PMID- 26272568 TI - Draft Genome Sequence and Annotation of Phyllosphere-Persisting Salmonella enterica subsp. enterica Serovar Livingstone Strain CKY-S4, Isolated from an Urban Lake in Regina, Canada. AB - Here, we report the first draft genome sequence of Salmonella enterica subsp. enterica serovar Livingstone. This S. Livingstone strain CKY-S4 displayed biofilm formation and cellulose production and could persist on lettuce. This genome may help the study of mechanisms by which enteric pathogens colonize food crops. PMID- 26272569 TI - Genome Sequence and Annotation of Trichoderma parareesei, the Ancestor of the Cellulase Producer Trichoderma reesei. AB - The filamentous fungus Trichoderma parareesei is the asexually reproducing ancestor of Trichoderma reesei, the holomorphic industrial producer of cellulase and hemicellulase. Here, we present the genome sequence of the T. parareesei type strain CBS 125925, which contains genes for 9,318 proteins. PMID- 26272570 TI - Complete Genome Sequence of Staphylococcus aureus FCFHV36, a Methicillin Resistant Strain Heterogeneously Resistant to Vancomycin. AB - We report here the sequence of the entire chromosome of Staphylococcus aureus strain FCFHV36, a methicillin-resistant strain heterogeneously intermediate to vancomycin, bearing a type II staphylococcal chromosome cassette mec element (SCCmec), belonging to multilocus sequence type (MLST) 105, and isolated from a vertebra of a patient with osteomyelitis. PMID- 26272571 TI - Complete Genome Sequence of Paenibacillus sp. Strain VT 400, Isolated from the Saliva of a Child with Acute Lymphoblastic Leukemia. AB - We report here the complete genome sequence of spore-forming Paenibacillus sp. strain VT 400, isolated from the saliva of a child with acute lymphoblastic leukemia. The genome consists of 6,986,122 bp, with a G+C content of 45.8%. It possesses 5,777 predicted protein-coding genes encoding multidrug resistance transporters, virulence factors, and resistance to chemotherapeutic drugs. PMID- 26272572 TI - Draft Genome Sequence of Lactobacillus fermentum NB-22. AB - We announce here a draft genome sequence of Lactobacillus fermentum NB-22, a strain isolated from human vaginal microbiota. The assembled sequence consists of 190 contigs, joined into 137 scaffolds, and the total size is 2.01 Mb. PMID- 26272573 TI - Metagenome Sequencing of the Greater Kudu (Tragelaphus strepsiceros) Rumen Microbiome. AB - Ruminant herbivores utilize a symbiotic relationship with microorganisms in their rumen to exploit fibrous foods for nutrition. We report the metagenome sequences of the greater kudu (Tragelaphus strepsiceros) rumen digesta, revealing a diverse community of microbes and some novel hydrolytic enzymes. PMID- 26272574 TI - High-Quality Draft Genome Sequence of Francisella tularensis subsp. holarctica Strain OR96-0246. AB - The bacterial pathogen Francisella tularensis was recently renewed as a tier-one select agent. F. tularensis subsp. tularensis (type A) and holarctica (type B) are of clinical relevance. Here, we report the complete genome of a virulent F. tularensis type B strain and describe its usefulness in comparative genomics. PMID- 26272575 TI - Draft Genome Sequence of Neisseria gonorrhoeae Sequence Type 1407, a Multidrug Resistant Clinical Isolate. AB - Gonorrhea may become untreatable due to the spread of resistant or multidrug resistant strains. Cefixime-resistant gonococci belonging to sequence type 1407 have been described worldwide. We report the genome sequence of Neisseria gonorrhoeae strain G2891, a multidrug-resistant isolate of sequence type 1407, collected in Italy in 2013. PMID- 26272576 TI - Draft Genome Sequence of Acinetobacter calcoaceticus Strain GK1, a Hydrocarbon Degrading Plant Growth-Promoting Rhizospheric Bacterium. AB - The 3.94-Mb draft genome of Acinetobacter calcoaceticus GK1, a hydrocarbonoclastic plant growth-promoting Gram-negative rhizospheric bacterium, is presented here. Isolated at the Ford Motor Company site in Genk, Belgium, from poplar trees planted on a diesel-contaminated plume, GK1 is useful for enhancing hydrocarbon phytoremediation. PMID- 26272577 TI - Draft Genome Sequences of Leptospira santarosai Strains U160, U164, and U233, Isolated from Asymptomatic Cattle. AB - In the present work, we announce the draft genomes for three new strains (U160, U164, and U233) of Leptospira santarosai, isolated from urine samples from asymptomatic cattle in Rio de Janeiro, Brazil. PMID- 26272578 TI - Draft Genome Sequence of Purine-Degrading Clostridium cylindrosporum HC-1 (DSM 605). AB - Here, we report the draft genome sequence of Clostridium cylindrosporum HC-1, a purine- and glycine-fermenting anaerobe, which uses selenoprotein glycine reductase for substrate degradation. The genome consists of a single chromosome (2.72 Mb) and a circular plasmid (14.4 kb). PMID- 26272579 TI - Draft Genome Sequence of Bacillus pseudalcaliphilus PN-137T (DSM 8725), an Alkaliphilic Halotolerant Bacterium Isolated from Garden Soils. AB - Bacillus pseudalcaliphilus PN-137(T) (DSM 8725) is a Gram-positive, spore forming, alkaliphilic, and halotolerant bacterium. Here, we report the 4.49-Mb genome sequence of B. pseudalcaliphilus PN-137(T), which will accelerate the application of this alkaliphile and provide useful information for genomic taxonomy and phylogenomics of Bacillus-like bacteria. PMID- 26272580 TI - Genome Sequence of Anaerobacillus macyae JMM-4T (DSM 16346), the First Genomic Information of the Newly Established Genus Anaerobacillus. AB - Anaerobacillus macyae JMM-4(T) (DSM 16346) is a Gram-positive, spore-forming, strictly anaerobic, and arsenate-respiring bacterium. Here, we report the 4.26-Mb genome sequence of A. macyae JMM-4(T), which is the first genome information of the newly established genus Anaerobacillus. PMID- 26272581 TI - Soil Metagenomes from Different Pristine Environments of Northwest Argentina. AB - This is the first study to use a high-throughput metagenomic shotgun approach to explore the biosynthetic potential of soil metagenomes from different pristine environments of northwest Argentina. Our data sets characterize these metagenomes and provide information on the possible effect these ecosystems have on their diversity and biosynthetic potential. PMID- 26272582 TI - Incapacity of work after arthroscopic Bankart repair. AB - BACKGROUND AND INTRODUCTION: The incapacity with respect to work following anterior-inferior shoulder dislocation and subsequent Bankart repair has not been previously examined. The objective of this study was to examine a patient's incapacity according to the classification by the REFA Association. The recovery time was measured and the outcome of patients with heavy workload was compared to those with lower workloads. MATERIALS AND METHODS: A total of 74 patients who underwent isolated arthroscopic Bankart repair fulfilled the inclusion criteria. The Constant-Murley Score, UCLA Shoulder Score and ROWE Score for Shoulder Instability were recorded for clinical assessment. The mean follow-up time was 43.1 months (SD +/- 17.4; 24-110 months) with a mean age of 34.7 years (SD +/- 12.6). Workload was classified as per the REFA Association classification system. Postoperative duration of a patient's incapacity with respect to work and other subjective ratings were provided by the patients themselves. RESULTS: The mean incapacity of work was 2.73 months (95 % CI 1.19-5.36). The incapacity of work was 2.06 months (95 % CI 1.55-2.68) in the group with low physical strains at work (REFA 0-1) and 3.40 months (95 % CI 2.70-4.24) in the group with heavy workload (REFA 2-4/p = 0.005). Overall, the mean Constant-Murley Score was 87.7 (SD +/- 13.5). The average UCLA Shoulder Score summed up to 31.9 (SD +/- 3.87) and the mean ROWE Score was 87.6 (SD +/- 21.7). 13 (17.5 %) patients had problems to compete in their jobs. Three patients had to change the job postoperatively. CONCLUSION: In this study, a relationship between the time of incapacity of work and the workload was observed; patients with low physical strains returned significantly earlier to work after arthroscopic Bankart repair (p = 0.005). In general, the clinical results as measured in the Constant/UCLA/Rowe score were comparable to other studies. PMID- 26272583 TI - Influences of fit and fill following hip arthroplasty using a cementless short stem prosthesis. AB - INTRODUCTION: The purpose of this study consisted in examining the effects of fit and fill ratio of the Metha prosthesis (BBraun, Aesculap, Tuttlingen, Germany) on radiological and clinical outcomes at a follow-up of 1 year. METHODS: 40 patients were included. Fit and fill ratio measurements, radiological and clinical examinations were performed preoperatively and postoperatively. Correlations were established between fit and fill ratio, and potential factors like sex, age, body mass index, Harris Hip Score and changes of radiological signs. RESULTS: The whole cohort (100%) had a tight fit and fill ratio (>0.8) at the proximal level and at each follow-up. "Champagne-flute" configuration provoked high distal tight fit and fill ratio. Poor distal fit and fill ratio compared to the proximal and the mid-stem level was measurable at each follow-up (p < 0.05). Correlations between fit and fill ratio and preoperative femur configurations were detectable. CONCLUSIONS: Implanting the Metha prosthesis induces tight fit and fill ratio at the proximal and coated sections. Preoperative femur configuration should be considered to achieve best fit and fill situation and therefore excellent primary stability. In most cases "normal" and "stove-pipe" configurations provide good proximal fit and fill. Since "champagne-flute" configuration induces undesirable tight distal fit and fill ratio the size of the Metha ((r)) stem should be adequately increased to achieve a more proximal load transmission. PMID- 26272584 TI - Anaplastic astrocytoma mimicking herpes simplex encephalitis in 13-year old girl. AB - Astrocytoma is the most common childhood brain tumor. Anaplastic astrocytoma (AA) are high grade gliomas (HGG), found very rarely in pediatric patients. AA mainly results from a dedifferentiation of a low grade astrocytoma. Clinical features of supra-tentorial tumors vary according to their anatomic location, biologic aggressiveness and age of the patient. They can be either completely asymptomatic or present with signs of raised intracranial pressure, seizures (about 40% of cases), behavior changes, speech disorders, declining school performance, or hemiparesis. There have been published adult cases of brain tumor misdiagnosed as viral encephalitis. Due to variety of clinical presentations, diagnosis of AA can be challenging. Here we report a case of a 13 year old girl who presented with clinical features suggestive of viral encephalitis, such as fever, headache, dizziness, and first seizure with postictal sleep and prolonged drowsiness. However, her brain MRI findings were consistent with long standing mass effect from the underlying intracranial contents and that coupled with her history of unusual taste led to further investigations and the diagnosis of the AA. In retrospect, this presentation could have been a temporal epileptic aura. High grade astrocytomas are particularly difficult to treat with a two-year survival rates range from 10% to 30%. The treatment is multimodal with gross total surgical resection of the tumor, followed by radiotherapy with or without nitrosourea-containing chemotherapy regimen. Recent promising results seen with the use of temozolamide in adults has not been yet demonstrated in the pediatric patients. The extent of tumor resection remains the most significant indicator of survival and early recognition of this tumor is essential. This case report emphasizes the fact that mass lesions in the temporal lobe, including high-grade astrocytoma, should be considered in the differential diagnosis of suspected herpes simplex encephalitis, especially those not responding to therapy. Remodeling of the calvarium adjacent to an intracranial lesion suggests a long standing process. PMID- 26272585 TI - Review of laboratory-based terrestrial bioaccumulation assessment approaches for organic chemicals: Current status and future possibilities. AB - In the last decade, interest has been renewed in approaches for the assessment of the bioaccumulation potential of chemicals, principally driven by the need to evaluate large numbers of chemicals as part of new chemical legislation, while reducing vertebrate test organism use called for in animal welfare legislation. This renewed interest has inspired research activities and advances in bioaccumulation science for neutral organic chemicals in aquatic environments. In January 2013, ILSI Health and Environmental Sciences Institute convened experts to identify the state of the science and existing shortcomings in terrestrial bioaccumulation assessment of neutral organic chemicals. Potential modifications to existing laboratory methods were identified, including areas in which new laboratory approaches or test methods could be developed to address terrestrial bioaccumulation. The utility of "non-ecotoxicity" data (e.g., mammalian laboratory data) was also discussed. The highlights of the workshop discussions are presented along with potential modifications in laboratory approaches and new test guidelines that could be used for assessing the bioaccumulation of chemicals in terrestrial organisms. PMID- 26272586 TI - Effects of meal type on the oral bioavailability of the ALK inhibitor ceritinib in healthy adult subjects. AB - Ceritinib is a potent inhibitor of anaplastic lymphoma kinase (ALK), which has shown acceptable safety and substantial antitumor activity in ALK-positive non small cell lung cancer (NSCLC) patients. Two food-effect studies were conducted in healthy adults to investigate the influence of food on the oral bioavailability of ceritinib: a study with low- or high-fat meals at 500 mg and a study with a light snack at 750 mg. Compared with the fasted state, AUC0-infinity (90%CI) of ceritinib was increased by 58% (34%, 86%) after the intake of a low fat meal, by 73% (46%, 105%) after the intake of a high-fat meal, and by 54% (19%, 99%) after the intake of a light snack. Safety assessments also suggested that food may improve gastrointestinal (GI) tolerability after a single ceritinib dose. Based on the pharmacokinetic results, it is essential to avoid any type of meal during dosing of ceritinib because the intake of food may increase the occurrence of exposure-dependent, non-GI toxicities at the labeled dose of 750 mg daily during fasting. A randomized trial is ongoing to determine an alternative way to give ceritinib (450 mg or 600 mg with food) that may enhance GI tolerability in ALK-positive NSCLC patients. PMID- 26272587 TI - Morphoscopic Trait Expression in "Hispanic" Populations. AB - This study evaluates population variation of eight cranial morphoscopic traits using samples of known southwest Hispanics (n=72), Guatemalans (n=106), American Blacks (n=146), and American Whites (n=218). We applied the support vector machine (SVM) method to build a prediction model based on a subsample (20%) of the data; the remainder of the data was used as a test sample. The SVM approach effectively differentiated between the four groups with correct classification rates between 72% (Guatemalan group) and 94% (American Black group). However, when the Guatemalan and southwest Hispanic samples were pooled, the same model correctly classified all groups with a higher degree of accuracy (American Black=96%; American White=77%; and the pooled Hispanic sample=91%). This study also identified significant differences between the two Hispanic groups in six of the eight traits using univariate statistical tests. These results speak to the unique population histories of these samples and the current use of the term "Hispanic" within forensic anthropology. Finally, we argue that the SVM can be used as a classification model for ancestry estimation in a forensic context and as a diagnostic tool may broaden the application of morphoscopic trait data for the assessment of ancestry. PMID- 26272588 TI - Expanded carrier screening: too much of a good thing? PMID- 26272589 TI - Structure and extent of DNA methylation-based epigenetic variation in wild emmer wheat (T. turgidum ssp. dicoccoides) populations. AB - BACKGROUND: The genetic structure and differentiation of wild emmer wheat suggests that genetic diversity is eco-geographically structured. However, very little is known about the structure and extent of the heritable epigenetic variation and its influence on local adaptation in natural populations. RESULTS: The structure and extent of the heritable methylation-based epigenetic variation were assessed within and among natural populations of Triticum turgidum ssp. dicoccoides. We used methylation sensitive amplified polymorphism (MSAP) and transposon methylation display (TMD) techniques, to assess the methylation status of random genomic CCGG sites and CCGG sites flanking transposable elements (TEs), respectively. Both techniques were applied to the DNA of 50 emmer accessions which were collected from five different geographically isolated regions. In order to ensure the assessment of heritable epigenetic variation, all accessions were grown under common garden conditions for two generations. In all accessions, the difference in methylation levels of CCGG sites, including CCGG sites that flanked TEs, were not statistically significant and relatively high, ranging between 46 and 76 %. The pattern of methylation was significantly different among accessions, such that clear and statistically significant population-specific methylation patterns were observed. CONCLUSION: In this study, we have observed population-unique heritable methylation patterns in emmer wheat accessions originating from five geographically isolated regions. Our data indicate that methylation-based epigenetic diversity might be eco-geographically structured and might be partly determined by climatic and edaphic factors. PMID- 26272590 TI - Overexpression of BRCA1 or BRCA2 in prostatectomy specimens is predictive of biochemical recurrence after radical prostatectomy. AB - AIMS: To investigate the protein expressions of breast cancer 1 (BRCA1) and 2 (BRCA2) in prostatectomy specimens of localized prostate cancer (PC) patients, along with their associations with cancer characteristics and prognosis. METHODS AND RESULTS: Immunohistochemistry for BRCA1 and BRCA2 was performed on tissue microarrays of 510 PC cases treated from 2002 to 2012. The cytoplasmic immunoreactivity was scored for intensity, and clinicopathological parameters, including biochemical recurrence (BCR), were evaluated. During a median follow-up of 44 months, 128 patients developed BCR, with positive staining rates of 93.3% (n = 476) and 41.6% (n = 212) for BRCA1 and BRCA2, respectively, in the malignant tissues. The BRCA2 expression differed significantly between BCR-positive and BCR free cases [hazard ratio (HR): 1.75, P = 0.002]. BRCA1 and BRCA2 correlated significantly with age [odds ratio (OR): 0.131] and pN stage (OR: 6.00), pN stage (OR: 1.717) and BCR (OR: 1.972), respectively (P < 0.05). Multivariate analysis showed that BRCA1 (HR: 0.435), BRCA2 (HR: 2.45), pT3 stage (HR: 2.253), resection margin positivity (HR: 1.58), prostate size (HR: 0.975) and Gleason score (HR: 2.214-2.253) were independent predictors of BCR (P < 0.05). Moreover, BRCA2 correlated significantly with BCR-free survival (P = 0.0017). CONCLUSIONS: BRCA1 or BRCA2 overexpression is a significant predictive factor for BCR in PC patients. PMID- 26272592 TI - Energy-dependent gas-phase fragmentation of fluorofullerene multiply charged anions (MCAs). AB - Long-lived di- and trianions have been formed from fluorofullerenes in the gas phase by electrospray ionization. Fragmentation of multiply charged anions has been induced by multiple low-energy collisions. Two complementary dissociation experiments have been conducted. Firstly, unequivocal connectivity has been established between the precursor ion and the first and second generation of its product ions. Secondly, dianions have been studied in energy-resolved collisions, allowing the elucidation of the energetic demands of the dissociations. It was possible to study dianions with odd and even F numbers, possessing even and odd electron configurations, respectively. The fragmentation behavior is governed by the electronic stability of the anionic protagonists, in that ions with the less stable odd-electron configuration dissociate into species with the more stable even-electron configuration. Dianions with an odd electron count release an F atom to turn into an even electron system while retaining the charge state. Dianions with an even electron count undergo a more energy demanding charge separation reaction (Coulomb explosion) into an F(-) anion and an even electron monoanion. The studied trianions behave accordingly. F2 loss is prominent only with monoanions within an even-to-even electron fragmentation cascade. The trianions are long-lived with lifetimes of at least 0.1 s. PMID- 26272591 TI - Protein Kinase A-induced tamoxifen resistance is mediated by anchoring protein AKAP13. AB - BACKGROUND: Estrogen Receptor alpha (ERalpha)-positive breast cancer patients receive endocrine therapy, often in the form of tamoxifen. However, resistance to tamoxifen is frequently observed. A signalling cascade that leads to tamoxifen resistance is dictated by activation of the Protein Kinase A (PKA) pathway, which leads to phosphorylation of ERalpha on Serine 305 and receptor activation, following tamoxifen binding. Thus far, it remains elusive what protein complexes enable the PKA-ERalpha interaction resulting in ERalpha Serine 305 phosphorylation. METHODS: We performed immunohistochemistry to detect ERalphaSerine 305 phosphorylation in a cohort of breast cancer patients who received tamoxifen treatment in the metastatic setting. From the same tumor specimens, Agilent 44 K gene expression analyses were performed and integrated with clinicopathological data and survival information. In vitro analyses were performed using MCF7 breast cancer cells, which included immunoprecipitations and Fluorescence Resonance Energy Transfer (FRET) analyses to illustrate ERalpha complex formation. siRNA mediated knockdown experiments were performed to assess effects on ERalphaSerine 305 phosphorylation status, ERalpha/PKA interactions and downstream responsive gene activity. RESULTS: Stratifying breast tumors on ERalpha Serine 305 phosphorylation status resulted in the identification of a gene network centered upon AKAP13. AKAP13 mRNA expression levels correlate with poor outcome in patients who received tamoxifen treatment in the metastatic setting. In addition, AKAP13 mRNA levels correlate with ERalphaSerine 305 phosphorylation in breast tumor samples, suggesting a functional connection between these two events. In a luminal breast cancer cell line, AKAP13 was found to interact with ERalpha as well as with a regulatory subunit of PKA. Knocking down of AKAP13 prevented PKA-mediated Serine 305 phosphorylation of ERalpha and abrogated PKA-driven tamoxifen resistance, illustrating that AKAP13 is an essential protein in this process. CONCLUSIONS: We show that the PKA-anchoring protein AKAP13 is essential for the phosphorylation of ERalphaS305, which leads to tamoxifen resistance both in cell lines and tamoxifen-treated breast cancer patients. PMID- 26272593 TI - Effectiveness of prepregnancy care for women with pregestational diabetes mellitus: protocol for a systematic review of the literature and identification of a core outcomes set using a Delphi survey. AB - BACKGROUND: Women with pregnancy complicated by pregestational diabetes experience increased rates of adverse pregnancy outcomes. Prepregnancy care is the targeted support and additional care offered to those women who are planning pregnancy and is associated with improved outcomes. However, there is significant heterogeneity in the outcomes measured and reported in studies evaluating the effects of prepregnancy care, which makes meaningful comparison difficult. The aim of this article is to present a protocol for a study to develop a Core Outcome Set (COS) for trials and other studies evaluating the effectiveness of prepregnancy care for women with pregestational diabetes mellitus. METHODS/DESIGN: This study will include a systematic review of the literature to identify outcomes that have previously been reported in studies evaluating prepregnancy care for women with pregestational diabetes. We will then prioritise these outcomes from the perspective of key stakeholders, including women with pregestational diabetes as well as clinicians, using a Delphi survey. A final consensus meeting will be held with stakeholders to review and finalise the outcomes. DISCUSSION: The expectation is that the COS will always be collected and reported in all clinical trials, audits of practice and other forms of research that involve prepregnancy care programs for women with pregestational diabetes. This will facilitate comparing and contrasting of studies and allow for combining of appropriate studies with the ultimate goal of improved patient care. PMID- 26272595 TI - Models vs. Realities in Female Sexual Dysfunction. PMID- 26272594 TI - Laparoscopic Versus Open Loop Ileostomy Reversal: Is there an Advantage to a Minimally Invasive Approach? AB - BACKGROUND: Ileostomy reversals are commonly performed procedures after colon and rectal operations. Laparoscopic ileostomy reversal (LIR) with lysis of adhesions has potential benefits over conventional open surgery. The aim of this study was to compare outcomes of laparoscopic and open ileostomy reversal. METHODS: 133 consecutive patients undergoing ileostomy reversal at our institution between June 2009 and August 2013 were analyzed using a retrospective database. The group comprised 53 laparoscopic cases and 80 open cases, performed by four surgeons at a single center. The data were analyzed for patient demographics, operative characteristics, postoperative outcomes, and 30-day morbidity and mortality. RESULTS: The two groups had comparable mean age, gender distribution, ASA scores, and BMI. The laparoscopic group had a significantly longer duration of surgery compared to the open reversal group (109 versus 93 min, p < 0.05). However, this group underwent more lysis of adhesions (60.4 % versus 26.3 %, p < 0.01) as well as concurrent stoma site mesh reinforcement (32.1 % versus 6.3 %, p < 0.01). In the laparoscopy group, 20.7 % of patients underwent intra-corporeal ileo-ileal anastomosis. There were no significant differences between the laparoscopic and open groups with regard to estimated blood loss (31 versus 40 ml, respectively) or mean length of stay (5.3 vs. 5.7 days, respectively). The rates of overall 30 day morbidity (16.9 % for laparoscopic vs. 21.3 % for open) as well as rates of specific complications were equivalent between groups. 30-day mortalities were not noted in either group. CONCLUSION: LIR is safe and effective with low perioperative morbidity and mortality. The use of laparoscopy as an option in terms of concomitant hernia repair and lysis of adhesions may be considered in selected patients. PMID- 26272596 TI - Estimating Ixodes ricinus densities on the landscape scale. AB - BACKGROUND: The study describes the estimation of the spatial distribution of questing nymphal tick densities by investigating Ixodes ricinus in Southwest Germany as an example. The production of high-resolution maps of questing tick densities is an important key to quantify the risk of tick-borne diseases. Previous I. ricinus maps were based on quantitative as well as semi-quantitative categorisations of the tick density observed at study sites with different vegetation types or indices, all compiled on local scales. Here, a quantitative approach on the landscape scale is introduced. METHODS: During 2 years, 2013 and 2014, host-seeking ticks were collected each month at 25 sampling sites by flagging an area of 100 square meters. All tick stages were identified to species level to select nymphal ticks of I. ricinus, which were used to develop and calibrate Poisson regression models. The environmental variables height above sea level, temperature, relative humidity, saturation deficit and land cover classification were used as explanatory variables. RESULTS: The number of flagged nymphal tick densities range from zero (mountain site) to more than 1,000 nymphs/100 m(2). Calibrating the Poisson regression models with these nymphal densities results in an explained variance of 72 % and a prediction error of 110 nymphs/100 m(2) in 2013. Generally, nymphal densities (maximum 374 nymphs/100 m(2)), explained variance (46 %) and prediction error (61 nymphs/100 m(2)) were lower in 2014. The models were used to compile high-resolution maps with 0.5 km(2) grid size for the study region of the German federal state Baden Wurttemberg. The accuracy of the mapped tick densities was investigated by leave one-out cross-validation resulting in root-mean-square-errors of 227 nymphs/100 m(2) for 2013 and 104 nymphs/100 m(2) for 2014. CONCLUSIONS: The methodology introduced here may be applied to further tick species or extended to other study regions. Finally, the study is a first step towards the spatial estimation of tick-borne diseases in Central Europe. PMID- 26272598 TI - Prevalence of hepatitis B virus in primary central nervous system lymphoma. PMID- 26272597 TI - Increased in-hospital mortality following severe head injury in young children: results from a nationwide trauma registry. AB - BACKGROUND: In the current literature, the outcome of paediatric brain injury is controversially discussed. According to the majority of the studies, there seems to be a decreased mortality but worse recovery in paediatric, traumatic brain injury in comparison with adults. However, there is a lack of information concerning the differences in various stages of development in patients younger than 18 years. The aim of our study was to verify the in-hospital outcome of different paediatric age groups in comparison to adults with respect to the treatment strategy. METHODS: We performed a retrospective analysis of the TraumaRegister DGU((r)) from 2002 to 2012. Inclusion criteria were an Abbreviated Injury Scale (AIS) head >=3 points and an AIS <=2 points of the remaining body regions. The collective was divided into different subgroups according to age (1 3, 4-6, 7-10, 11-14, 15-17) and an adult control group aged between 18 and 55 years. We descriptively analysed the endpoint rate of sepsis, multiple organ failure, and mortality. Additionally, the Glasgow Outcome Scale (GOS) at discharge was observed. RESULTS: Overall, 1110 children and 6491 adult control patients were included. Comparing the rate of intubation on-scene, the rate of cranial CT scans, the rate of craniotomies, and the rate and length of intensive care treatment, we could only identify minor differences between the age groups. The treatment after discharge from hospital was markedly different due to a very low rate of in-patient rehabilitation treatment in children. On one hand, the rate of systemic complications, such as sepsis and multiple organ failure increased with increasing age. On the other hand, we found a significantly increased mortality in children younger than 7 years after very (AIS head = 5) severe brain injury. The in-hospital functional outcome in survivors, according to the GOS, was beneficial for younger children in comparison to adolescents and adults. CONCLUSIONS: We were unable to identify marked age-related differences in the therapeutic approach. Nevertheless, we were able to demonstrate marked differences of outcome. Children younger than 7 years significantly die more often due to direct impact of severe trauma. But if they survive, they seem to develop less systemic complications and profit from a better functional outcome. PMID- 26272599 TI - Ischemic stroke in patients with gliomas at The University of Texas-M.D. Anderson Cancer Center. AB - Patients with gliomas are at risk of cerebrovascular accidents (CVA) with potential consequences on survival, function, and local tumor control. Our objective was to provide information about CVA in patients with gliomas and to estimate survival in this group. We reviewed all adult glioma patients with ischemic CVA at the University of Texas-M.D. Anderson Cancer Center from 2003 through 2014. We extracted demographic, clinical, imaging, treatment and outcome data. We used descriptive summary data and estimated or compared survival rates where appropriate. 60 of 6500 patients (0.1%) with high-grade (HGG, n = 47) or low-grade glioma (LGG, n = 13) had ischemic CVA Thirty-two (53%) patients had postoperative strokes, and 20 (33%) had CVA after 2 weeks of surgery. Forty-one patients (68%) had gross total resection. For HGG and CVA, the poststroke median overall survival was 17 months versus 61 months in LGG and CVA (P = 0.03; hazard ratio (HR): 2.8; 95% CI 1.07-4.60). Survival stratified by modified Rankin Scale grade was significant (X(2) = 9.8, P = 0.007). Five patients received bevacizumab before stroke onset; none responded to antiangiogenic therapy. There was no stroke-related death. At our institution for 10 years, ischemic CVA in glioma patients was a rare complication, clearly associated in half of cases to surgery, and with a variable negative impact on performance status and neurologic function. In this group, patients with more neurological deficits lived less. The survival difference between and within subgroups was most likely due to tumor grade. More research is necessary to improve prevention of postoperative stroke in glioma patients. PMID- 26272600 TI - Detection of proneural/mesenchymal marker expression in glioblastoma: temporospatial dynamics and association with chromatin-modifying gene expression. AB - Proneural and mesenchymal are two subtypes of glioblastoma identified by gene expression profiling. In this study, the primary aim was to detect markers to develop a clinically applicable method for distinguishing proneural and mesenchymal glioblastoma. The secondary aims were to investigate the temporospatial dynamics of these markers and to explore the association between these markers and the expression of chromatin-modifying genes. One hundred thirty three glioma samples (grade II: 14 samples, grade III: 18, grade IV: 101) were analyzed. We quantified the expression of 6 signature genes associated with proneural and mesenchymal glioblastoma by quantitative reverse transcription polymerase chain reaction. We assigned proneural (PN) and mesenchymal (MES) scores based on the average of the 6 markers and calculated a predominant metagene (P-M) score by subtracting the MES from the PN score. We used these scores to analyze correlations with malignant transformation, tumor recurrence, tumor heterogeneity, chromatin-modifying gene expression, and HDAC7 expression. The MES score positively correlated with tumor grade, whereas the PN score did not. The P-M score was able to distinguish the proneural and mesenchymal subtypes. It was decreased in cases of tumor recurrence and malignant transformation and showed variability within a tumor, suggesting intratumoral heterogeneity. The PN score correlated with the expression of multiple histone modifying genes, whereas the MES score was associated only with HDAC7 expression. Thus, we demonstrated a simple and straightforward method of quantifying proneural/mesenchymal markers in glioblastoma. Of note, HDAC7 expression might be a novel therapeutic target in glioblastoma treatment. PMID- 26272602 TI - Immunogenicity and safety of an inactivated quadrivalent influenza vaccine in healthy adults: a phase II, open-label, uncontrolled trial in Japan. AB - Two antigenically distinct B strain lineages of influenza virus have co circulated since the mid-1980s; however, inactivated trivalent influenza vaccines contain only one B lineage. The mismatch between the circulating and vaccine lineages has been a worldwide issue. In this study, an inactivated quadrivalent influenza vaccine (QIV) candidate containing two B lineages was manufactured and its immunogenicity and safety evaluated in an open-label, uncontrolled trial. In this phase II trial, 50 subjects aged 20-64 years received two doses of QIV s.c. 1 to 4 weeks apart. Sera were collected pre- and post-vaccination and safety assessed from the first vaccination to 21 +/- 7 days after the second vaccination. After the first vaccination, hemagglutination inhibition titers against each strain increased markedly; the seroconversion rate, geometric mean titer ratio and seroprotection rate being 94.0%, 24.93, and 100.0%, respectively, for the A/H1N1pdm09 strain; 94.0%, 12.47, and 98.0%, respectively, for the A/H3N2 strain; 54.0%, 4.99, and 66.0%, respectively, for B/Yamagata strain, and 72.0%, 6.23 and 80.0%, respectively, for the B/Victoria strain, thus fulfilling the criteria of the European Medical Agency's Committee for Medicinal Products for Human Use. Also, the QIV induced sufficient single radial hemolysis and neutralizing antibodies against all four vaccine strains. No noteworthy adverse events were noted. The results of this trial demonstrate that QIV is well tolerated and immunogenic for each strain, suggesting that QIV potentially improves protection against influenza B by resolving the issue of B lineage mismatch. PMID- 26272601 TI - miR-429 inhibits glioma invasion through BMK1 suppression. AB - The purpose of this research was to examine the relationship between big mitogen activated protein kinase 1 (BMK1) and miRNA miR-429 and to determine the effect of miR-429 on glioma invasiveness. Immunohistochemistry was used to evaluate BMK1 expression in glioma tissues. Real-time PCR was used to measure the expression of miR-429 and other RNAs. Western blot was used to detect the expression of BMK1 and other related proteins. Wound healing, Matrigel invasion, and chemotaxis assays were performed to detect the invasion and migration of glioma cell lines. The actual binding site of miR-429 to the 3' untranslated region of BMK1 was confirmed by luciferase assay and RNA immunoprecipitation. BMK1 expression was associated with the World Health Organization grading of glioma and inversely correlated with patient survival. Suppression of BMK1 inhibited the migration and invasion of glioma cells by interfering with mesenchymal transition. Additionally, hepatocyte growth factor-induced GSK3beta phosphorylation was suppressed through BMK1 knockdown. Interestingly, our findings validated a novel role for miR-429 in suppressing the migration and invasion of glioma by directly inhibiting BMK1 expression. We also found that miR-429 expression in glioma cells and tissues was lower than that in normal cells and adjacent non-neoplastic tissues, and miR-429 overexpression inhibited invasive activity of glioma cells both in vitro and in vivo. Furthermore, our data validated that miR-429 downregulation was due to the hypermethylation of its promoter region. Our results indicated that BMK1 modulation by miR-429 has an important function in glioma invasion both in vitro and in vivo. PMID- 26272603 TI - Transient receptor potential melastatin 8 gene polymorphism is associated with cold-induced airway hyperresponsiveness in bronchial asthma. AB - BACKGROUND AND OBJECTIVE: Cold-induced airway hyperresponsiveness (CAH) is common in bronchial asthma (BA) patients and represents a problem for those living in cold climate. Transient receptor potential melastatin 8 (TRPM8) channel is the main cold temperature sensor in humans that could mediate cold response in asthmatics with CAH. No associations between TRPM8 gene polymorphisms and CAH have been reported. METHODS: The present study involved 123 BA patients. CAH was assessed by 3-min isocapnic (5% CO2 ) cold air (-20 degrees C) hyperventilation challenge. The c.750G > C (rs11562975), c.1256G > A (rs7593557), c.3048C > T (rs11563208) and c.3174C > G (rs11563071) polymorphisms of TRPM8 gene were genotyped by allele-specific polymerase chain reaction (PCR) and PCR with subsequent restriction fragment length polymorphism analysis. RESULTS: GC genotype and C allele carriers of the c.750G > C (rs11562975) polymorphism were more frequently observed to exhibit CAH. The estimated odds ratio for the GC genotype was 3.73 95%CI (1.48; 9.37), P = 0.005. Furthermore, GC heterozygotes had a prominent decrease in forced expiratory volume in 1 s after the challenge as compared to GG homozygotes (-12% (-16; -8.1) vs -6.45% (-11; -2.1), P < 0.001). GC carriers also had a marked reduction in other spirometric parameters. CONCLUSIONS: The GC variant of the TRPM8:c.750G > C (rs11562975) polymorphism is associated with CAH in patients with BA, which suggests a potential role of TRPM8 in CAH development. PMID- 26272604 TI - Tuning the Magnetic Interactions and Relaxation Dynamics of Dy2 Single-Molecule Magnets. AB - Efficient modulation of single-molecule magnet (SMM) behavior was realized by deliberate structural modification of the Dy2 cores of [Dy2(a'povh)2(OAc)2(DMF)2] (1) and [Zn2Dy2(a'povh)2(OAc)6]?4 H2O (2; H2a'povh = N'-[amino(pyrimidin-2 yl)methylene]-o-vanilloyl hydrazine). Compound 1 having fourfold linkage between the two dysprosium ions shows high-performance SMM behavior with a thermal energy barrier of 322.1 K, whereas only slow relaxation is observed for compound 2 with only twofold connection between the dysprosium ions. This remarkable discrepancy is mainly because of strong axiality in 1 due to one pronounced covalent bond, as revealed by experimental and theoretical investigations. The significant antiferromagnetic interaction derived from bis(MU2-O) and two acetate bridging groups was found to be crucial in leading to a nonmagnetic ground state in 1, by suppressing zero-field quantum tunneling of magnetization. PMID- 26272605 TI - Disseminated intravascular coagulation in non-Hodgkin lymphoma. AB - The present study analyzed the incidence and clinical features of disseminated intravascular coagulation (DIC) developed in association with non-Hodgkin lymphoma (NHL). Two hundred thirty-six patients with newly diagnosed NHL were admitted to our institute since Jul. 2008 to Dec. 2014. Coagulation markers were evaluated in 161 of 236 patients at the time of diagnosis. DIC was diagnosed in 18 patients (11.2 %) based on the criteria established by Ministry of Health, Labor, and Welfare of Japan. All of the 18 patients had Ann-Arbor Stage IV advanced disease, and 17 patients were in poor performance status. Liver function panels, such as bilirubin, aminotransferases, serum choline esterase, and albumin levels, were worse in patients with DIC than those without DIC, indicating impaired production of coagulation factors. Importantly, DIC exerts significantly negative impact on prognosis of NHL; median survival of both groups was 176 versus 2430 days. The difference remains significant after statistically adjusting for age, performance status, Ann-Arbor stage, international prognostic index, and liver function panels. Nine of 18 patients with DIC received anti coagulants, which failed to improve clinical outcome. Nevertheless, early recognition and intervention to DIC state may contribute to improve prognosis of NHL. PMID- 26272606 TI - Neurocardiovascular instability may modulate end-organ damage: A review of this hypothesis investigating the eye and manifestations of NCVI. AB - Neurocardiovascular instability (NCVI) represents age-related changes in blood pressure and heart rate behaviour. It has been associated with increased leukoaraiosis in the brain and also conditions which are likely to be are related to cerebral end-organ damage, such as stroke and falls. The eye is a 'window' into the brain and cardiovascular (CV) system, changes in retinal microvasculature being independently predictive of cardiovascular events. The eye is highly vascular, having two circulatory systems and as such the ideal target end-organ to investigate NCVI and early end-organ damage. The retinal and choroidal circulations of the eye would be vulnerable to NCVI if ocular vasoregulation becomes impaired with age, particularly given the high metabolic activity of the retina. The choroid is predominantly extrinsically regulated by the autonomic nervous system. In patients with NCVI, autonomic dysfunction is more common and thus impairment of the tightly regulated ocular microcirculation may indeed be compromised. We review the evidence for the hypothesis that NCVI may modulate end-organ cardiovascular pathology and that the eye is the ideal target organ to monitor this. PMID- 26272607 TI - Blood pressure and risk of cancer progression - A possible connection with salt and voltage-gated sodium channel. AB - Although it is well known that high blood pressure promotes cancer, the underlying cause(s) is not well understood. Here, we advance the hypothesis that the extracellular sodium level could be a contributing factor. The hypothesis is based upon emerging evidence showing (i) that voltage-gated sodium channels are expressed de novo in cancer cells and tissues, and (ii) that the influx of sodium from the extracellular medium into cancer cells, mediated by the channel activity, promotes their metastatic potential. Clinical and lifestyle implications of the hypothesis are discussed. PMID- 26272608 TI - Development of a polymerase chain reaction assay for the rapid detection of the oral pathogenic bacterium, Selenomonas noxia. AB - BACKGROUND: In recent studies, periodontal health has been linked to being overweight and/or obese. Among common oral bacteria, Selenomonas noxia has been implicated in converting periodontal health to disease, and Selenomonas species have also been found in gastric ulcers. The objective of this study was to develop and validate a quantitative polymerase chain reaction (qPCR) assay for the specific and rapid detection of S. noxia. METHODS: Two oligonucleotide primer pairs and one probe were designed and tested to determine optimal amplification signal with three strains of S. noxia. The PCR assay was tested against fourteen non-target organisms, including closely related oral Selenomonads, one phylogenetically closely related bacterium, and two commonly isolated oral bacteria. RESULTS: One of the primer sets was more sensitive at detecting the target organism and was selected for optimization and validation experiments. The designed primers and probe amplified the target organism with 100% specificity. PCR inhibition was observed with an internal positive control, and inhibition was resolved by diluting the DNA extract. CONCLUSIONS: The qPCR assay designed in this study can be used to specifically detect S. noxia in the clinical setting and in future research involving the enhanced detection of S. noxia. The assay can also be used in epidemiological studies for understanding the role of S. noxia in disease processes including, but not limited to, oral health and obesity of infectious origin. PMID- 26272609 TI - Inhibition of oncogenic epidermal growth factor receptor kinase triggers release of exosome-like extracellular vesicles and impacts their phosphoprotein and DNA content. AB - Cancer cells emit extracellular vesicles (EVs) containing unique molecular signatures. Here, we report that the oncogenic EGF receptor (EGFR) and its inhibitors reprogram phosphoproteomes and cargo of tumor cell-derived EVs. Thus, phosphorylated EGFR (P-EGFR) and several other receptor tyrosine kinases can be detected in EVs purified from plasma of tumor-bearing mice and from conditioned media of cultured cancer cells. Treatment of EGFR-driven tumor cells with second generation EGFR kinase inhibitors (EKIs), including CI-1033 and PF-00299804 but not with anti-EGFR antibody (Cetuximab) or etoposide, triggers a burst in emission of exosome-like EVs containing EGFR, P-EGFR, and genomic DNA (exo-gDNA). The EV release can be attenuated by treatment with inhibitors of exosome biogenesis (GW4869) and caspase pathways (ZVAD). The content of P-EGFR isoforms (Tyr-845, Tyr-1068, and Tyr-1173), ERK, and AKT varies between cells and their corresponding EVs and as a function of EKI treatment. Immunocapture experiments reveal the presence of EGFR and exo-gDNA within the same EV population following EKI treatment. These findings suggest that targeted agents may induce cancer cells to change the EV emission profiles reflective of drug-related therapeutic stress. We suggest that EV-based assays may serve as companion diagnostics for targeted anticancer agents. PMID- 26272610 TI - Catalysis of GTP hydrolysis by small GTPases at atomic detail by integration of X ray crystallography, experimental, and theoretical IR spectroscopy. AB - Small GTPases regulate key processes in cells. Malfunction of their GTPase reaction by mutations is involved in severe diseases. Here, we compare the GTPase reaction of the slower hydrolyzing GTPase Ran with Ras. By combination of time resolved FTIR difference spectroscopy and QM/MM simulations we elucidate that the Mg(2+) coordination by the phosphate groups, which varies largely among the x-ray structures, is the same for Ran and Ras. A new x-ray structure of a Ran.RanBD1 complex with improved resolution confirmed this finding and revealed a general problem with the refinement of Mg(2+) in GTPases. The Mg(2+) coordination is not responsible for the much slower GTPase reaction of Ran. Instead, the location of the Tyr-39 side chain of Ran between the gamma-phosphate and Gln-69 prevents the optimal positioning of the attacking water molecule by the Gln-69 relative to the gamma-phosphate. This is confirmed in the RanY39A.RanBD1 crystal structure. The QM/MM simulations provide IR spectra of the catalytic center, which agree very nicely with the experimental ones. The combination of both methods can correlate spectra with structure at atomic detail. For example the FTIR difference spectra of RasA18T and RanT25A mutants show that spectral differences are mainly due to the hydrogen bond of Thr-25 to the alpha-phosphate in Ran. By integration of x ray structure analysis, experimental, and theoretical IR spectroscopy the catalytic center of the x-ray structural models are further refined to sub-A resolution, allowing an improved understanding of catalysis. PMID- 26272611 TI - A Novel Basal Body Protein That Is a Polo-like Kinase Substrate Is Required for Basal Body Segregation and Flagellum Adhesion in Trypanosoma brucei. AB - The Polo-like kinase (PLK) in Trypanosoma brucei plays multiple roles in basal body segregation, flagellum attachment, and cytokinesis. However, the mechanistic role of TbPLK remains elusive, mainly because most of its substrates are not known. Here, we report a new substrate of TbPLK, SPBB1, and its essential roles in T. brucei. SPBB1 was identified through yeast two-hybrid screening with the kinase-dead TbPLK as the bait. It interacts with TbPLK in vitro and in vivo, and is phosphorylated by TbPLK in vitro. SPBB1 localizes to both the mature basal body and the probasal body throughout the cell cycle, and co-localizes with TbPLK at the basal body during early cell cycle stages. RNAi against SPBB1 in procyclic trypanosomes inhibited basal body segregation, disrupted the new flagellum attachment zone filament, detached the new flagellum, and caused defective cytokinesis. Moreover, RNAi of SPBB1 confined TbPLK at the basal body and the bilobe structure, resulting in constitutive phosphorylation of TbCentrin2 at the bilobe. Altogether, these results identified a basal body protein as a TbPLK substrate and its essential role in promoting basal body segregation and flagellum attachment zone filament assembly for flagellum adhesion and cytokinesis initiation. PMID- 26272612 TI - A Novel GLP1 Receptor Interacting Protein ATP6ap2 Regulates Insulin Secretion in Pancreatic Beta Cells. AB - GLP1 activates its receptor, GLP1R, to enhance insulin secretion. The activation and transduction of GLP1R requires complex interactions with a host of accessory proteins, most of which remain largely unknown. In this study, we used membrane based split ubiquitin yeast two-hybrid assays to identify novel GLP1R interactors in both mouse and human islets. Among these, ATP6ap2 (ATPase H(+)-transporting lysosomal accessory protein 2) was identified in both mouse and human islet screens. ATP6ap2 was shown to be abundant in islets including both alpha and beta cells. When GLP1R and ATP6ap2 were co-expressed in beta cells, GLP1R was shown to directly interact with ATP6ap2, as assessed by co-immunoprecipitation. In INS-1 cells, overexpression of ATP6ap2 did not affect insulin secretion; however, siRNA knockdown decreased both glucose-stimulated and GLP1-induced insulin secretion. Decreases in GLP1-induced insulin secretion were accompanied by attenuated GLP1 stimulated cAMP accumulation. Because ATP6ap2 is a subunit required for V-ATPase assembly of insulin granules, it has been reported to be involved in granule acidification. In accordance with this, we observed impaired insulin granule acidification upon ATP6ap2 knockdown but paradoxically increased proinsulin secretion. Importantly, as a GLP1R interactor, ATP6ap2 was required for GLP1 induced Ca(2+) influx, in part explaining decreased insulin secretion in ATP6ap2 knockdown cells. Taken together, our findings identify a group of proteins that interact with the GLP1R. We further show that one interactor, ATP6ap2, plays a novel dual role in beta cells, modulating both GLP1R signaling and insulin processing to affect insulin secretion. PMID- 26272613 TI - Identification of the Flavonoid Luteolin as a Repressor of the Transcription Factor Hepatocyte Nuclear Factor 4alpha. AB - Hepatocyte nuclear factor 4alpha (HNF4alpha) is a nuclear receptor that regulates the expression of genes involved in the secretion of apolipoprotein B (apoB) containing lipoproteins and in glucose metabolism. In the present study, we identified a naturally occurring flavonoid, luteolin, as a repressor of HNF4alpha by screening for effectors of the human microsomal triglyceride transfer protein (MTP) promoter. Luciferase reporter gene assays revealed that the activity of the MTP gene promoter was suppressed by luteolin and that the mutation of HNF4alpha binding element abolished luteolin responsiveness. Luteolin treatment caused a significant decrease in the mRNA levels of HNF4alpha target genes in HepG2 cells and inhibited apoB-containing lipoprotein secretion in HepG2 and differentiated Caco2 cells. The interaction between luteolin and HNF4alpha was demonstrated using absorption spectrum analysis and luteolin-immobilized beads. Luteolin did not affect the DNA binding of HNF4alpha to the promoter region of its target genes but suppressed the acetylation level of histone H3 in the promoter region of certain HNF4alpha target genes. Short term treatment of mice with luteolin significantly suppressed the expression of HNF4alpha target genes in the liver. In addition, long term treatment of mice with luteolin significantly suppressed their diet-induced obesity and improved their serum glucose and lipid parameters. Importantly, long term luteolin treatment lowered serum VLDL and LDL cholesterol and serum apoB protein levels, which was not accompanied by fat accumulation in the liver. These results suggest that the flavonoid luteolin ameliorates an atherogenic lipid profile in vivo that is likely to be mediated through the inactivation of HNF4alpha. PMID- 26272614 TI - Microprocessor complex subunit DiGeorge syndrome critical region gene 8 (Dgcr8) is required for schwann cell myelination and myelin maintenance. AB - We investigated the role of a key component of the Microprocessor complex, DGCR8, in the regulation of myelin formation and maintenance. We found that conditionally ablating Dgcr8 in Schwann cells (SCs) during development results in an arrest of SC differentiation. Dgcr8 conditional knock-out (cKO) SCs fail to form 1:1 relationships with axons or, having achieved this, fail to form myelin sheaths. The expression of genes normally found in immature SCs, such as sex determining region Y-box 2 (Sox2), is increased in Dgcr8 cKO SCs, whereas the expression of myelin-related genes, including the master regulatory transcription factor early growth response 2 (Egr2), is decreased. Additionally, expression of a novel gene expression program involving sonic hedgehog (Shh), activated de novo in injured nerves, is elevated in Dgcr8 cKOs but not in Egr2 null mice, a model of SC differentiation arrest, suggesting that the injury-related gene expression program in Dgcr8 cKOs cannot be attributed to differentiation arrest. Inducible ablation of Dgcr8 in adult SCs results in gene expression changes similar to those found in cKOs, including an increase in the expression of Sox2 and Shh. Analyses of these nerves mainly reveal normal myelin thickness and axon size distribution but some dedifferentiated SCs and increased macrophage infiltration. Together our data suggest that Dgcr8 is responsible for modulation of gene expression programs underlying myelin formation and maintenance as well as suppression of an injury-related gene expression program. PMID- 26272615 TI - Unliganded fibroblast growth factor receptor 1 forms density-independent dimers. AB - Fibroblast growth factors receptors (FGFRs) are thought to initiate intracellular signaling cascades upon ligand-induced dimerization of the extracellular domain. Although the existence of unliganded FGFR1 dimers on the surface of living cells has been proposed, this notion remains rather controversial. Here, we employed time-resolved Forster resonance energy transfer combined with SNAP- and ACP-tag labeling in COS7 cells to monitor dimerization of full-length FGFR1 at the cell surface with or without the coreceptor betaKlotho. Using this approach we observed homodimerization of unliganded FGFR1 that is independent of its surface density. The homo-interaction signal observed for FGFR1 was indeed as robust as that obtained for epidermal growth factor receptor (EGFR) and was further increased by the addition of activating ligands or pathogenic mutations. Mutational analysis indicated that the kinase and the transmembrane domains, rather than the extracellular domain, mediate the ligand-independent FGFR1 dimerization. In addition, we observed a formation of a higher order ligand independent complex by the c-spliced isoform of FGFR1 and betaKlotho. Collectively, our approach provides novel insights into the assembly and dynamics of the full-length FGFRs on the cell surface. PMID- 26272618 TI - Intensified fractionation of brewery yeast waste for the recovery of invertase using aqueous two-phase systems. AB - The potential recovery of high-value products from brewery yeast waste confers value to this industrial residue. Aqueous two-phase systems (ATPS) have demonstrated to be an attractive alternative for the primary recovery of biological products and are therefore suitable for the recovery of invertase from this residue. Sixteen different polyethylene glycol (PEG)-potassium phosphate ATPS were tested to evaluate the effects of PEG molecular weight (MW) and tie line length (TLL) upon the partition behavior of invertase. Concentrations of crude extract from brewery yeast waste were then varied in the systems that presented the best behaviors to intensify the potential recovery of the enzyme. Results show that the use of a PEG MW 400 g mol-1 system with a TLL of 45.0% (w/w) resulted in an invertase bottom phase recovery with a purification factor of 29.5 and a recovery yield of up to 66.2% after scaling the system to a total weight of 15.0 g. This represents 15.1 mg of invertase per mL of processed bottom phase. With these results, a single-stage ATPS process for the recovery of invertase is proposed. PMID- 26272619 TI - The potential Public Health Impact of Mycobacterium avium ssp. paratuberculosis: Global Opinion Survey of Topic Specialists. AB - Global research knowledge has accumulated over the past few decades, and there is reasonable evidence for a positive association between Mycobacterium avium spp. paratuberculosis and Crohn's disease in humans, although its role as a human pathogen has not been entirely accepted. For this reason, management of public health risk due to M. paratuberculosis remains an important policy issue in agri food public health arenas in many countries. Responsible authorities must decide whether existing mitigation strategies are sufficient to prevent or reduce human exposure to M. paratuberculosis. A Web-based questionnaire was administered to topic specialists to elicit empirical knowledge and opinion on the overall public health impact of M. paratuberculosis, the importance of various routes of human exposure to the pathogen, existing mitigation strategies and the need for future strategies. The questionnaire had four sections and consisted of 20 closed and five open questions. Topic specialists believed that M. paratuberculosis is likely a risk to human health (44.8%) and, given the paucity of available evidence, most frequently ranked it as a moderate public health issue (40.1%). A significant correlation was detected between topic specialists' commitment to M. paratuberculosis in terms of the number of years or proportion of work dedicated to this topic, and the likelihood of an extreme answer (high or low) to the above questions. Topic specialists identified contact with ruminants and dairy products as the most likely routes of exposure for humans. There was consensus on exposure routes for ruminants and what commodities to target in mitigation efforts. Described mandatory programmes mainly focused on culling diseased animals and voluntary on-farm prevention programmes. Despite ongoing difficulties in the identification of subclinical infections in animals, the topic specialists largely agreed that further enhancement of on-farm programmes in affected commodities by the agri-food industry (68.4%) and allocation of resources by governments to monitor the issue (92%) are most appropriate given the current state of evidence. PMID- 26272616 TI - Degenerate connective polypeptide 1 (CP1) domain from human mitochondrial leucyl tRNA synthetase. AB - The connective polypeptide 1 (CP1) editing domain of leucyl-tRNA synthetase (LeuRS) from various species either harbors a conserved active site to exclude tRNA mis-charging with noncognate amino acids or is evolutionarily truncated or lost because there is no requirement for high translational fidelity. However, human mitochondrial LeuRS (hmtLeuRS) contains a full-length but degenerate CP1 domain that has mutations in some residues important for post-transfer editing. The significance of such an inactive CP1 domain and a translational accuracy mechanism with different noncognate amino acids are not completely understood. Here, we identified the essential role of the evolutionarily divergent CP1 domain in facilitating hmtLeuRS's catalytic efficiency and endowing enzyme with resistance to AN2690, a broad-spectrum drug acting on LeuRSs. In addition, the canonical core of hmtLeuRS is not stringent for noncognate norvaline (Nva) and valine (Val). hmtLeuRS has a very weak tRNA-independent pre-transfer editing activity for Nva, which is insufficient to remove mis-activated Nva. Moreover, hmtLeuRS chimeras fused with a functional CP1 domain from LeuRSs of other species, regardless of origin, showed restored post-transfer editing activity and acquired fidelity during aminoacylation. This work offers a novel perspective on the role of the CP1 domain in optimizing aminoacylation efficiency. PMID- 26272617 TI - The cysteine dioxygenase homologue from Pseudomonas aeruginosa is a 3 mercaptopropionate dioxygenase. AB - Thiol dioxygenation is the initial oxidation step that commits a thiol to important catabolic or biosynthetic pathways. The reaction is catalyzed by a family of specific non-heme mononuclear iron proteins each of which is reported to react efficiently with only one substrate. This family of enzymes includes cysteine dioxygenase, cysteamine dioxygenase, mercaptosuccinate dioxygenase, and 3-mercaptopropionate dioxygenase. Using sequence alignment to infer cysteine dioxygenase activity, a cysteine dioxygenase homologue from Pseudomonas aeruginosa (p3MDO) has been identified. Mass spectrometry of P. aeruginosa under standard growth conditions showed that p3MDO is expressed in low levels, suggesting that this metabolic pathway is available to the organism. Purified recombinant p3MDO is able to oxidize both cysteine and 3-mercaptopropionic acid in vitro, with a marked preference for 3-mercaptopropionic acid. We therefore describe this enzyme as a 3-mercaptopropionate dioxygenase. Mossbauer spectroscopy suggests that substrate binding to the ferrous iron is through the thiol but indicates that each substrate could adopt different coordination geometries. Crystallographic comparison with mammalian cysteine dioxygenase shows that the overall active site geometry is conserved but suggests that the different substrate specificity can be related to replacement of an arginine by a glutamine in the active site. PMID- 26272620 TI - Assessment of net knee moment-angle characteristics by instrumented hand-held dynamometry in children with spastic cerebral palsy and typically developing children. AB - BACKGROUND: The limited range of motion during walking in children with spastic cerebral palsy (SCP) may be the result of altered mechanical characteristics of muscles and connective tissues around the knee joint. Measurement of static net knee moment-angle relation will provide insights into these alterations, for which instrumented hand-held dynamometry may be applied. The aims of this study were: (1) to test the measurement error of the estimated net knee moment-angle characteristics, (2) to determine the correlation between knee extension angle measurement at a standardized knee moment and popliteal angle from common physical examination and (3) to compare net knee moment-angle characteristics in SCP versus typically developing children. METHODS: With the child lying in sideward position, the knee was extended by moving the lower leg by a hand-held force transducer on a low friction cart. Force data were collected for a range of knee angles. Data were excluded when activity (EMG) levels of knee extensor and flexor muscles exceeded the EMG level during rest by more than two standard deviations. The net knee flexion moments were calculated from recorded force data and measured moment arm. Reliability for knee angles corresponding with 0.5, 1, 2, 3, and 4 Nm knee net flexion moments was assessed by standard error of measurements (SEM) and smallest detectable difference (SDD). RESULTS: For between day comparison, SEMs were about 5 degrees and SDDs were below 14 degrees for knee angles at 1-4 Nm net knee flexion moments. In SCP children, the knee angle measured at 4 Nm knee flexion moment was not related to the popliteal angle (r = 0.52). The slope at 4 Nm of the knee moment-angle curve in SCP children was significantly higher than that in typically developing children. CONCLUSIONS: The presented knee hand-held dynamometry allows assessment of net knee flexion moment knee angle characteristics in typically developing and SCP children and can be used to identify clinically relevant changes as a result of treatment. Overall stiffness of structures that contribute to the net knee flexion moment at the knee (i.e. muscles, tendons, ligaments) is elevated in SCP children. PMID- 26272621 TI - Audiovisual distraction as a useful adjunct to epidural anesthesia and sedation for prolonged lower limb microvascular orthoplastic surgery. AB - Lower limb orthopedic operations are frequently performed under regional anesthesia, which allows avoidance of potential side effects and complications of general anesthesia and sedation. Often though, patients feel anxious about being awake during operations. To decrease intraoperative anxiety, we use multimedia equipment consisting of a tablet device, noise-canceling headphones, and a makeshift frame, where patients can listen to music, watch movies, or occupy themselves in numerous ways. These techniques have been extensively studies in minimally invasive, short, or minor procedures but not in prolonged orthoplastic operations. We report 2 cases where audiovisual distraction was successfully applied to 9.5-hour procedures, proved to be a very useful adjunct to epidural anesthesia + sedation, and made an important contribution to positive patients' outcomes and overall patients' experience with regional anesthesia for complex limb reconstructive surgery. In the era when not only patients' safety and clinical outcomes but also patients' positive experiences are of paramount importance, audiovisual distraction may provide a simple tool to help improve experience of appropriately informed patients undergoing suitable procedures under regional anesthesia. The anesthetic technique received a very positive appraisal by both patients and encouraged us to study further the impact of modern audiovisual technology on anxiolysis for major surgery under regional anesthesia. The duration of surgery per se is not a contraindication to the use of audiovisual distraction. The absolute proviso of successful application of this technique to major surgery is effective regional anesthesia and good teamwork between the clinicians and the patients. PMID- 26272622 TI - MyD88 mediates in vivo effector functions of alveolar macrophages in acute lung inflammatory responses to carbon nanotube exposure. AB - Carbon nanotubes (CNTs) are rapidly emerging as high-priority occupational toxicants. CNT powders contain fibrous particles that aerosolize readily in places of manufacture and handling, posing an inhalation risk for workers. Studies using animal models indicate that lung exposure to CNTs causes prolonged inflammatory responses and diffuse alveolar injury. The mechanisms governing CNT induced lung inflammation are not fully understood but have been suggested to involve alveolar macrophages (AMs). In the current study, we sought to systematically assess the effector role of AMs in vivo in the induction of lung inflammatory responses to CNT exposures and investigate their cell type-specific mechanisms. Multi-wall CNTs characterized for various physicochemical attributes were used as the CNT type. Using an AM-specific depletion and repopulation approach in a mouse model, we unambiguously demonstrated that AMs are major effector cells necessary for the in vivo elaboration of CNT-induced lung inflammation. We further investigated in vitro AM responses and identified molecular targets which proved critical to pro-inflammatory responses in this model, namely MyD88 as well as MAPKs and Ca(2+)/CamKII. We further demonstrated that MyD88 inhibition in donor AMs abrogated their capacity to reconstitute CNT induced inflammation when adoptively transferred into AM-depleted mice. Taken together, this is the first in vivo demonstration that AMs act as critical effector cell types in CNT-induced lung inflammation and that MyD88 is required for this in vivo effector function. AMs and their cell type-specific mechanisms may therefore represent potential targets for future therapeutic intervention of CNT-related lung injury. PMID- 26272624 TI - Putting heterosynaptic plasticity in its place - as easy as PIE. PMID- 26272623 TI - Genome-wide association study of body weight in Australian Merino sheep reveals an orthologous region on OAR6 to human and bovine genomic regions affecting height and weight. AB - BACKGROUND: Body weight (BW) is an important trait for meat production in sheep. Although over the past few years, numerous quantitative trait loci (QTL) have been detected for production traits in cattle, few QTL studies have been reported for sheep, with even fewer on meat production traits. Our objective was to perform a genome-wide association study (GWAS) with the medium-density Illumina Ovine SNP50 BeadChip to identify genomic regions and corresponding haplotypes associated with BW in Australian Merino sheep. METHODS: A total of 1781 Australian Merino sheep were genotyped using the medium-density Illumina Ovine SNP50 BeadChip. Among the 53 862 single nucleotide polymorphisms (SNPs) on this array, 48 640 were used to perform a GWAS using a linear mixed model approach. Genotypes were phased with hsphase; to estimate SNP haplotype effects, linkage disequilibrium blocks were identified in the detected QTL region. RESULTS: Thirty nine SNPs were associated with BW at a Bonferroni-corrected genome-wide significance threshold of 1 %. One region on sheep (Ovis aries) chromosome 6 (OAR6) between 36.15 and 38.56 Mb, included 13 significant SNPs that were associated with BW; the most significant SNP was OAR6_41936490.1 (P = 2.37 * 10( 16)) at 37.69 Mb with an allele substitution effect of 2.12 kg, which corresponds to 0.248 phenotypic standard deviations for BW. The region that surrounds this association signal on OAR6 contains three genes: leucine aminopeptidase 3 (LAP3), which is involved in the processing of the oxytocin precursor; NCAPG non-SMC condensin I complex, subunit G (NCAPG), which is associated with foetal growth and carcass size in cattle; and ligand dependent nuclear receptor corepressor like (LCORL), which is associated with height in humans and cattle. CONCLUSIONS: The GWAS analysis detected 39 SNPs associated with BW in sheep and a major QTL region was identified on OAR6. In several other mammalian species, regions that are syntenic with this region have been found to be associated with body size traits, which may reflect that the underlying biological mechanisms share a common ancestry. These findings should facilitate the discovery of causative variants for BW and contribute to marker-assisted selection. PMID- 26272625 TI - Coupling cellular metabolism to neuronal signalling. PMID- 26272626 TI - Squamous Cell Carcinoma: Clinical and Pathological Features and Associated Risk Factors in an Observational Study of 118 Patients. AB - BACKGROUND AND OBJECTIVE: In the latest edition of its cancer staging manual, the American Joint Committee on Cancer (AJCC) revised the criteria for staging squamous cell carcinoma (SCC) by introducing high-risk tumor features to define tumor stage (T) and help to identify tumors with a higher risk of metastasis. The aim of this study was to investigate the characteristics associated with SCC meeting the high-risk criteria defined by the AJCC for T2 lesions. PATIENTS AND METHOD: We performed a case-case observational study in which patients with SCC were included over a period of 18 months. We collected clinical, anthropometric, and tumor data, and analyzed these using PASW Statistics (SPSS) version 18. RESULTS: One-hundred eighteen patients, the majority of whom were men, were included. Mean age was 77 years. Over 70% of the tumors were located in the head region and a majority of tumors measured 2 cm or less. The prevalence of SCC T2 was 61.9%. The risk factors significantly associated with SCC T2 were an age of over 85 years (odds ratio [OR], 4.48), location in the head and neck region (OR, 3.38), presence of solar elastosis in the peritumoral tissue (OR, 2.08), a higher tumor growth rate (>1.5 mm.wk(-1); OR, 5.73), and higher cumulative exposure to smoking (>20 pack-years, OR, 3.63). CONCLUSIONS: Advanced age, location in the head and neck region, presence of solar elastosis, high tumor growth rate, and high cumulative smoking exposure were all significantly associated with the presence of SCC T2. PMID- 26272627 TI - Risky traditional practices and prevention of mother-to-child transmission of HIV: the case of Chiota community in Zimbabwe. AB - The objective of this study was to explore cultural practices that could expose babies to HIV infection during the postnatal period in Chiota community in Zimbabwe. Purposively selected and gender disaggregated members of the community (n = 231) were informants to 23 focus group discussions and 8 semi-structured key informant interviews. Data were analysed thematically. Emerging themes relating to risky practices were rituals surrounding open fontanelle, toning of child's sexual libido, initiation of sex after childbirth, treatment of eye and ear infections, tongue-tie and pre-mastication. These practices exposed babies to bodily fluids such as saliva, breast milk, vaginal fluids, pre-cum and semen which in turn put the babies at low to high risk of contracting HIV. This paper discusses implications for these risky practices in prevention of mother-to-child transmission of HIV. There is, therefore, need for studies to establish the prevalence of these practices. PMID- 26272628 TI - Biometric measurements involving the terminal portion of the thoracic duct on left cervical level IV: an anatomic study. AB - To determine the point of entrance of the thoracic duct in the venous system, as well as to evaluate some biometric measurements concerning its terminal portion, we conducted an anatomic study on 25 non-preserved cadavers. The termination of the thoracic duct occurred on the confluence between the left internal jugular vein and the left subclavian vein in 60 % of the individuals. The average results for the biometric measurements were: distance between the end of left internal jugular vein and omohyoid muscle 31.2 +/- 2.7 mm; distance between the end of thoracic duct and the left internal jugular vein 0.0 +/- 0.0 mm; distance between the end of thoracic duct and the left subclavian vein 3.6 +/- 1.0 mm; distance between the end of thoracic duct and the left brachiocephalic vein 10.7 +/- 3.1 mm. Moreover, it was identified that the left internal jugular vein length in level IV, measured between its entrance in the left subclavian vein and the omohyoid muscle, was able to predict the termination of the thoracic duct on the junction between the left internal jugular vein and the left subclavian vein (OR = 2.99) with high accuracy (79.3 %). In addition, the left internal jugular vein length at level IV was able to predict the localization of thoracic duct termination. Thus, this finding has practical value in minimizing the risk for a potential chyle leak during or after a left-sided neck dissection. PMID- 26272630 TI - Orthokeratotic Bowen disease: a histopathologic, immunohistochemical and molecular study. AB - BACKGROUND: Some examples of Bowen disease lack the characteristic broad parakeratosis making their histopathologic diagnosis particularly difficult in small and incomplete biopsies. MATERIALS AND METHODS: The archives of our dermatopathology laboratory were searched for cases of Bowen disease with >75% orthokeratosis (orthokeratotic Bowen disease) and classic Bowen disease (>25% parakeratosis). Selected specimens were evaluated histopathologically, using immunohistochemical stains (CK10, CK7, Bcl-2, p16 and Ki-67) and by DNA amplification/sequencing for human papilloma virus (HPV) subtypes. RESULTS: Among 102 consecutive samples 14 cases of orthokeratotic Bowen disease were identified. In comparison with 24 examples of classic Bowen disease, the orthokeratotic examples occurred more frequently in female and younger patients (p = 0.04 and 0.008, respectively) but shared most of the histopathologic features of classic Bowen disease except a preserved granular layer and relative absence of the eyeliner sign (p < 0.0001 and p = 0.042, respectively). Immunohistochemical staining patterns were similar between the two groups. HPV types 11, 16 and 58 were identified from five cases of orthokeratotic Bowen disease. CONCLUSION: Orthokeratotic Bowen disease is a distinct variant of squamous cell carcinoma in situ associated with HPV infection in less than half of the cases studied. PMID- 26272629 TI - A short N-terminal domain of HDAC4 preserves photoreceptors and restores visual function in retinitis pigmentosa. AB - Retinitis pigmentosa is a leading cause of inherited blindness, with no effective treatment currently available. Mutations primarily in genes expressed in rod photoreceptors lead to early rod death, followed by a slower phase of cone photoreceptor death. Rd1 mice provide an invaluable animal model to evaluate therapies for the disease. We previously reported that overexpression of histone deacetylase 4 (HDAC4) prolongs rod survival in rd1 mice. Here we report a key role of a short N-terminal domain of HDAC4 in photoreceptor protection. Expression of this domain suppresses multiple cell death pathways in photoreceptor degeneration, and preserves even more rd1 rods than the full-length HDAC4 protein. Expression of a short N-terminal domain of HDAC4 as a transgene in mice carrying the rd1 mutation also prolongs the survival of cone photoreceptors, and partially restores visual function. Our results may facilitate the design of a small protein therapy for some forms of retinitis pigmentosa. PMID- 26272632 TI - Psychometric Properties of a German Translation of the PROMIS(r) Depression Item Bank. AB - The patient-reported outcome measurement information system (PROMIS(r)) initiative has developed and evaluated a set of publicly available, efficient, and flexible measures of patient-reported outcomes in different health domains, including mental health. The objective of this study was to translate the PROMIS Depression item bank into German and evaluate the psychometric properties of the translated items. Items were translated using forward and backward translation and cognitive interviews. Distribution characteristics, unidimensionality, Rasch model fit, reliability, construct validity, and internal responsiveness were investigated in a sample of 234 patients in in-patient psychosomatic rehabilitation centers in Germany. The translated items showed good psychometric properties, the distribution characteristics were satisfactory, and the sufficient unidimensionality was obtained by fitting a bifactor model. The construct validity was demonstrated, and it was reliable and was shown to detect clinically significant changes. The translated items can be recommended for the assessment of depression. Future studies should examine the generalizability of the results. PMID- 26272631 TI - Exosomes or microvesicles? Two kinds of extracellular vesicles with different routes to modify protozoan-host cell interaction. AB - Parasite-host cell interaction can be modulated by a dynamic communication between extracellular vesicles (EVs). They should play key roles in cell-cell communications transferring biomolecules (miRNA, proteins, soluble factors) from one cell to another cell. While many names have been used to denominate EVs, a better comprehension to understand these vesicles is raised when we classify it according to biogenesis: originated from multivesicular bodies, named exosomes, and from plasmatic membranes, denominated microvesicles. Here, we have reviewed EV participation during the protozoan-host cell interaction and reinforced the differences and similarities between exosomes and microvesicles, suggesting different intracellular routes and functions. We also discussed perspectives to study EVs and the role of EVs in diagnosis and chemotherapies of infectious diseases. PMID- 26272633 TI - Phenotypic and Genetic Variations in Obligate Parthenogenetic Populations of Eriosoma lanigerum Hausmann (Hemiptera: Aphididae). AB - The study of phenotypic and genetic variation of obligate parthenogenetic organisms contributes to an understanding of evolution in the absence of genetic variation produced by sexual reproduction. Eriosoma lanigerum Hausmann undergoes obligate parthenogenesis in Mexico City, Mexico, due to the unavailability of the host plants required for sexual reproduction. We analysed the phenotypic and genetic variation of E. lanigerum in relation to the dry and wet season and plant phenology. Aphids were collected on two occasions per season on a secondary host plant, Pyracantha koidzumii, at five different sites in the southern area of Mexico City, Mexico. Thirteen morphological characteristics were measured from 147 to 276 individuals per site and per season. A multivariate analysis of variance was performed to test the effect of the season, site and their interaction on morphological traits. Morphological variation was summarised using a principal component analysis. Genetic variation was described using six enzymatic loci, four of which were polymorphic. Our study showed that the site and season has a significant effect on morphological trait variation. The largest aphids were recorded during cold temperatures with low relative humidity and when the plant was at the end of the fruiting period. The mean genetic diversity was low (mean H e = .161), and populations were genetically structured by season and site. Morphological and genetic variations appear to be associated with environmental factors that directly affect aphid development and/or indirectly by host plant phenology. PMID- 26272634 TI - Rapid detection of ermB gene in Clostridium difficile by loop-mediated isothermal amplification. AB - Macrolide-lincosamide-streptogramin B resistance in Clostridium difficile is mostly due to the ermB resistance determinant. Here, we describe a sensitive and rapid molecular method to detect ermB in C. difficile to contribute to the wider epidemiological study. Five sets of loop-mediated isothermal amplification (LAMP) primers were designed and optimized for rapid detection of ermB. The specificity and sensitivity of the primers for ermB were detected, and the ermB LAMP assay was compared to conventional PCR with 80 clinical isolates of C. difficile. Real time monitoring of turbidity and chromogenic reaction were used to determine negative and positive results. A total of 26 pathogenic bacterial strains of different species were found to be negative for ermB, which indicated the high specificity of the primers. ermB was detected in 78.8 % (63/80) of the clinical isolates by both LAMP and conventional PCR. The detection limit of LAMP was 36.1 pg DNA MUl- 1 and its sensitivity was 10-fold greater than that of conventional PCR. This study is the first report regarding the development and application of the LAMP assay for detection of the ermB gene in C. difficile strains. The developed LAMP method is sensitive, specific and provides a user-friendly visual approach for the rapid detection of ermB-bearing C. difficile. PMID- 26272635 TI - Intracranial dural arteriovenous fistula associated with a spinal tumor: a case report. PMID- 26272636 TI - Differential modulation of resistance biomarkers in skin of juvenile and mature pink salmon, Oncorhynchus gorbuscha by the salmon louse, Lepeophtheirus salmonis. AB - Juvenile pink salmon larger than 0.7 g reject the sea louse, Lepeophtheirus salmonis, and are considered resistant to the infection. Robust innate defense responses in the skin contribute to the observed resistance. In contrast adult pink salmon captured at sea or shortly before spawning carry large numbers of the parasite, suggesting inability to control the infection. The purpose of this research is to better understand these apparently contradictory conclusions by comparing a suite of genetic and cellular markers of resistance to L. salmonis in the skin of juvenile and mature pink salmon. The expression of major histocompatibility factor II, C-reactive protein, interleukin-1beta, interleukin 8 and cyclooxygenase-2 was down-regulated in mature but not juvenile pink salmon. Similarly, skin at the site of parasite attachment in juvenile salmon was highly populated with MHIIbeta(+) and IL-1beta(+) cells that were either absent, or at reduced levels at similar sites in mature salmon. In addition, mucocyte density was relatively low in the skin of mature salmon, irrespective of louse infection. In juveniles, the higher mucocyte density decreased following louse attachment. We show that in mature pink salmon, genetic and histological responses in skin are depressed and speculate that salmonid defense against L. salmonis is modulated by maturation. PMID- 26272637 TI - Vitamin A supplementation enhances Senegalese sole (Solea senegalensis) early juvenile's immunocompetence: New insights on potential underlying pathways. AB - Senegalese sole (Solea senegalensis) has been considered since the 1990's to be a promising flatfish species for diversifying European marine aquaculture. However, pathogen outbreaks leading to high mortality rates can impair Senegalese sole commercial production at the weaning phase. Different approaches have been shown to improve fish immunocompetence; with this in mind the objective of the work described herein was to determine whether increased levels of dietary vitamin A (VA) improve the immune response in early juveniles of Senegalese sole. For this purpose, Senegalese sole were reared and fed with Artemia metanauplii containing increased levels of VA (37,000; 44,666; 82,666 and 203,000 total VA IU Kg(-1)) from 6 to 60 days post-hatch (early juvenile stage). After an induced bacterial infection with a 50% lethal dose of Photobacterium damselae subsp. damselae, survival rate, as well as underlying gene expression of specific immune markers (C1inh, C3, C9, Lgals1, Hamp, LysC, Prdx1, Steap4 and Transf) were evaluated. Results showed that fish fed higher doses of dietary VA were more resistant to the bacterial challenge. The lower mortality was found to be related with differential expression of genes involved in the complement system and iron availability. We suggest that feeding metamorphosed Senegalese sole with 203,000 total VA IU Kg(-1) might be an effective, inexpensive and environmentally friendly method to improve Senegalese sole immunocompetence, thereby improving survival of juveniles and reducing economic losses. PMID- 26272638 TI - Identification of a novel clip domain serine proteinase (Sp-cSP) and its roles in innate immune system of mud crab Scylla paramamosain. AB - Clip domain serine proteinases and their homologs are involved in the innate immunity of invertebrates. To identify the frontline defense molecules against pathogenic infection, we isolated a novel clip domain serine proteinase (Sp-cSP) from the hemocytes of mud crab Scylla paramamosain. The full-length 1362 bp Sp cSP contains a 1155 bp open reading frame (ORF) encoding 384 amino acids. Multiple alignment analysis showed that the putative amino acid sequence of Sp cSP has about 52% and 51% identity with Pt-cSP2 (AFA42360) and Pt-cSP3 (AFA42361) from Portunus trituberculatus, respectively, while the similarity with other cSP sequences was lower than 30%. However, all cSP sequences possess a conserved clip domain at the N-terminal and a Tryp-SPc domain at the C-terminal. The genomic organization of Sp-cSP consists of nine exons and eight introns, with some introns containing one or more tandem repeats. RT-PCR results indicated that Sp cSP transcripts were predominantly expressed in the subcuticular epidermis, muscle and mid-intestine, but barely detectable in the brain and heart. Further, Sp-cSP transcripts were significantly up-regulated after challenge with lipopolysaccharides (LPS), Vibrio parahaemolyticus, polyinosinic polycytidylic acid (PolyI:C) or white spot syndrome virus (WSSV). Moreover, in vitro, the recombinant Sp-cSP revealed a strong antimicrobial activity against a Gram positive (Staphylococcus aureus) and four Gram-negative (V. parahaemolyticus, Vibrio alginolyticus, Escherichia coli, Aeromonas hydrophila) bacteria in a dose dependent manner. Taken together, the acute-phase response to immune challenges and the antimicrobial activity assay indicate that Sp-cSP is a potent immune protector and plays an important role in host defense against pathogen invasion in S. paramamosain. PMID- 26272639 TI - Determine the structure of phosphorylated modification of icariin and its antiviral activity against duck hepatitis virus A. AB - BACKGROUND: Our previous research showed that icariin (1) and its phosphorylated structural modification (2) improved the survival and attenuated oxidative stress and liver dysfunction induced by duck virus hepatitis. In this paper, we were one step closer to determine the structure of phosphorylation icariin (2) by the FT IR, HRESIMS and (13)C NMR. Anti-DHAV activities of 1 and 2 were compared in duck embryonic hepatocytes (DEHs) cultured in vitro and by artificial infection method in vivo. Additionally, the antiviral mechanisms of replication/release in vitro and the DHAV gene expression in vivo of 1 and 2 were analyzed. RESULTS: Compound 2's molecular formula was C33H42O18P. The results indicated that 1 and 2 effectively resisted DHAV invading DEHs, that they decreased the mortality of ducklings challenged with DHAV, and that 2 performed more effectively. 1 and 2 performed evenly on DHAV release; however, 2 restrained virus replication far more effectively. Since the anti-DHAV mechanisms of 1 and 2 in vitro probably involve suppression of replication and release, 2's better performance in anti DHAV may result from its far more effectively inhibiting virus replication. CONCLUSIONS: The compound 2's chemical structure was defined as 8 prenylkaempferol-4'-methylether-3-rhamnosyl-7-(6'''-phosphate)-glycoside. 1 and 2 exhibited anti-virus activity on DHAV. Our results suggest that 1 and 2 might become an anti-virus plant material candidate. PMID- 26272640 TI - Antiplatelet drugs in patients with enhanced platelet turnover: biomarkers versus platelet function testing. AB - Platelets are key players in atherothrombosis. Antiplatelet therapy comprising aspirin alone or with P2Y12-inhibitors are effective for prevention of atherothrombotic complications. However, there is interindividual variability in the response to antiplatelet drugs, leaving some patients at increased risk of recurrent atherothrombotic events. Several risk factors associated with high on treatment platelet reactivity (HTPR), including elevated platelet turnover, have been identified. Platelet turnover is adequately estimated from the fraction of reticulated platelets. Reticulated platelets are young platelets, characterised by residual messenger RNA. They are larger, haemostatically more active and there is evidence that platelet turnover is a causal and prognostic factor in atherothrombotic disease. Whether platelet turnover per se represents a key factor in pathogenesis, progression and prognosis of atherothrombotic diseases (with focus on acute coronary syndromes) or whether it merely facilitates insufficient platelet inhibition will be discussed in this state-of-the art review. PMID- 26272641 TI - Effects of chronic exposure to 950 MHz ultra-high-frequency electromagnetic radiation on reactive oxygen species metabolism in the right and left cerebral cortex of young rats of different ages. AB - PURPOSE: To assess the effect of 950 MHz ultra-high-frequency electromagnetic radiation (UHF-EMR) on biomarkers of oxidative damage to DNA, proteins and lipids in the left cerebral cortex (LCC) and right cerebral cortex (RCC) of neonate and 6-day-old rats. MATERIALS AND METHODS: Twelve rats were equally divided into two groups as controls (CR) and exposed (ER), for each age (0 and 6 days). The LCC and RCC were examined in ER and CR after exposure. Radiation exposure lasted 30 min per day for up to 27 days (throughout pregnancy and 6 days postnatal). The specific absorption rate ranged from 1.32-1.14 W/kg. The damage to lipids, proteins and DNA was verified by thiobarbituric acid reactive substances, carbonylated proteins (CP) and comets, respectively. The concentration of glucose in the peripheral blood of the rats was measured by the Accu-Chek Active Kit due to increased CP in RCC. RESULTS: In neonates, no modification of the biomarkers tested was detected. On the other hand, there was an increase in the levels of CP in the RCC of the 6-day-old ER. Interestingly, the concentration of blood glucose was decreased in this group. CONCLUSIONS: Our results indicate that there is no genotoxicity and oxidative stress in neonates and 6 days rats. However, the RCC had the highest concentration of CP that do not seem to be a consequence of oxidative stress. This study is the first to demonstrate the use of UHF-EMR causes different damage responses to proteins in the LCC and RCC. PMID- 26272642 TI - Flavocoxid attenuates gentamicin-induced nephrotoxicity in rats. AB - Gentamicin is a widely used antibiotic against serious and life-threatening infections; however, its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine whether flavocoxid has a protective effect against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of flavocoxid on gentamicin induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was determined. Twenty-four male Wistar albino rats were randomly divided into three groups, namely control, gentamicin (100 mg/kg, i.p.) and gentamicin plus flavocoxid (20 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood, urine samples and kidneys were collected for further analysis. Gentamicin administration caused a severe nephrotoxicity which was evidenced by an elevated renal somatic index (RSI), serum creatinine, blood urea nitrogen, serum lactate dehydrogenase, and protein in urine with a concomitant reduction in serum albumin and normalized creatinine clearance value as compared with the controls. Moreover, a significant increase in renal contents of malondialdehyde, myeloperoxidase, and tumor necrosis factor-alpha with a significant decrease in renal reduced glutathione and superoxide dismutase activities was detected upon gentamicin administration together with increasing the sensitivity of isolated urinary bladder rings to ACh. Exposure to gentamicin induced necrosis of renal tubular epithelial cells. Flavocoxid protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by gentamicin treatment. In addition, flavocoxid significantly reduced the responses of isolated bladder rings to ACh. The results from our study indicate that flavocoxid supplement attenuates gentamicin-induced renal injury via the amelioration of oxidative stress and inflammation of renal tubular cells. PMID- 26272645 TI - Assessment of Protective Gloves for Use with Airfed Suits. AB - Gloves are often needed for hand protection at work, but they can impair manual dexterity, especially if they are multilayered or ill-fitting. This article describes two studies of gloves to be worn with airfed suits (AFS) for nuclear decommissioning or containment level 4 (CL4) microbiological work. Both sets of workers wear multiple layers of gloves for protection and to accommodate decontamination procedures. Nuclear workers are also often required to wear cut resistant gloves as an extra layer of protection. A total of 15 subjects volunteered to take part in manual dexterity testing of the different gloving systems. The subjects' hands were measured to ensure that the appropriate sized gloves were used. The gloves were tested with the subjects wearing the complete clothing ensembles appropriate to the work, using a combination of standard dexterity tests: the nine-hole peg test; a pin test adapted from the European Standard for protective gloves, the Purdue Pegboard test, and the Minnesota turning test. Specialized tests such as a hand tool test were used to test nuclear gloves, and laboratory-type manipulation tasks were used to test CL4 gloves. Subjective assessments of temperature sensation and skin wettedness were made before and after the dexterity tests of the nuclear gloves only. During all assessments, we made observations and questioned the subjects about ergonomic issues related to the clothing ensembles. Overall, the results show that the greater the thickness of the gloves and the number of layers the more the levels of manual dexterity performance are degraded. The nuclear cut-resistant gloves with the worst level of dexterity were stiff and inflexible and the subjects experienced problems picking up small items and bending their hands. The work also highlighted other factors that affect manual dexterity performance, including proper sizing, interactions with the other garments worn at the time, and the work equipment in use. In conclusion, when evaluating gloves for use in the workplace it is important to use tests that reflect the working environment and always to consider the balance between protection and usability. PMID- 26272646 TI - Dental Pulp Cell Behavior in Biomimetic Environments. AB - There is emerging recognition of the importance of a physiologically relevant in vitro cell culture environment to promote maintenance of stem cells for tissue engineering and regenerative medicine purposes. In vivo, appropriate cellular cues are provided by local tissue extracellular matrix (ECM), and these are not currently recapitulated well in vitro using traditional cultureware. We therefore hypothesized that better replication of the in vivo environment for cell culture and differentiation could be achieved by culturing dental pulp cells with their associated ECM. Primary dental pulp cells were subsequently seeded onto pulp derived ECM-coated cultureware. While at up to 24 h they exhibited the same level of adherence as those cells seeded on tissue culture-treated surfaces, by 4 d cell numbers and proliferation rates were significantly decreased in cells grown on pulp ECM compared with controls. Analysis of stem cell and differentiation marker transcripts, as well as Oct 3/4 protein distribution, supported the hypothesis that cells cultured on ECM better maintained a stem cell phenotype compared with those cultured on standard tissue culture-treated surfaces. Subsequent differentiation analysis of cells cultured on ECM demonstrated that they exhibited enhanced mineralization, as determined by alizarin red staining and mineralized marker expression. Supplementation of a 3% alginate hydrogel with pulp ECM components and dental pulp cells followed by differentiation induction in mineralization medium resulted in a time-dependent mineral deposition at the periphery of the construct, as demonstrated histologically and using micro computed tomography analysis, which was reminiscent of tooth structure. In conclusion, data indicate that culture of pulp cells in the presence of ECM better replicates the in vivo environment, maintaining a stem cell phenotype suitable for downstream tissue engineering applications. PMID- 26272647 TI - Erratum: Differential immune mechanism to HIV-1 Tat variants and its regulation by AEA. PMID- 26272644 TI - Deconstructing chronic low back pain in the older adult--Step by step evidence and expert-based recommendations for evaluation and treatment part III: Fibromyalgia syndrome. AB - OBJECTIVE: To present the third in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. The series presents CLBP as a syndrome, a final common pathway for the expression of multiple contributors rather than a disease localized exclusively to the lumbosacral spine. Each article addresses one of 12 important contributors to pain and disability in older adults with CLBP. This article focuses on fibromyalgia syndrome (FMS). METHODS: A modified Delphi approach was used to create the evaluation and treatment algorithm, the table discussing the rationale behind each of the algorithm components, and the stepped-care drug recommendations. The team involved in the creation of these materials consisted of a principal investigator, a 5-member content expert panel, and a 9-member primary care panel. The evaluation and treatment recommendations were based on availability of medications and other resources within the Veterans Health Administration (VHA) facilities. However, non-VHA panelists were also involved in the development of these materials, which can be applied to both VA and civilian settings. The illustrative clinical case was taken from the clinical practice of the principal investigator. RESULTS: Following expert consultations and a review of the literature, we developed an evaluation and treatment algorithm with supporting materials to aid in the care of older adults with CLBP who have concomitant FMS. A case is presented that demonstrates the complexity of pain evaluation and management in older patients with CLBP and concomitant FMS. CONCLUSIONS: Recognition of FMS as a common contributor to CLBP in older adults and initiating treatment targeting both FMS and CLBP may lead to improved outcomes in pain and disability. PMID- 26272648 TI - Multiple risk factor interventions for primary prevention of cardiovascular disease in low- and middle-income countries. AB - BACKGROUND: In many low- and middle-income countries (LMICs) morbidity and mortality associated with cardiovascular diseases (CVDs) have grown exponentially over recent years. It is estimated that about 80% of CVD deaths occur in LMICs. People in LMICs are more exposed to cardiovascular risk factors such as tobacco, and often do not have access to effective and equitable healthcare services (including early detection services). Evidence from high-income countries indicates that multiple risk factor intervention programmes do not result in reductions in CVD events. Given the increasing incidence of CVDs and lower CVD health awareness in LMICs it is possible that such programmes may have beneficial effects. OBJECTIVES: To determine the effectiveness of multiple risk factor interventions (with or without pharmacological treatment) aimed at modifying major cardiovascular risk factors for the primary prevention of CVD in LMICs. SEARCH METHODS: We searched (from inception to 27 June 2014) the Cochrane Library (CENTRAL, HTA, DARE, EED), MEDLINE, EMBASE, Global Health and three other databases on 27 June 2014. We also searched two clinical trial registers and conducted reference checking to identify additional studies. We applied no language limits. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of health promotion interventions to achieve behaviour change (i.e. smoking cessation, dietary advice, increasing activity levels) with or without pharmacological treatments, which aim to alter more than one cardiovascular risk factor (i.e. diet, reduce blood pressure, smoking, total blood cholesterol or increase physical activity) of at least six months duration of follow-up conducted in LMICs. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility and risk of bias, and extracted data. We combined dichotomous data using risk ratios (RRs) and continuous data using mean differences (MDs), and presented all results with a 95% confidence interval (CI). The primary outcome was combined fatal and non-fatal cardiovascular disease events. MAIN RESULTS: Thirteen trials met the inclusion criteria and are included in the review. All studies had at least one domain with unclear risk of bias. Some studies were at high risk of bias for random sequence generation (two trials), allocation concealment (two trials), blinding of outcome assessors (one trial) and incomplete outcome data (one trial). Duration and content of multiple risk factor interventions varied across the trials. Two trials recruited healthy participants and the other 11 trials recruited people with varying risks of CVD, such as participants with known hypertension and type 2 diabetes. Only one study reported CVD outcomes and multiple risk factor interventions did not reduce the incidence of cardiovascular events (RR 0.57, 95% CI 0.11 to 3.07, 232 participants, low-quality evidence); the result is imprecise (a wide confidence interval and small sample size) and makes it difficult to draw a reliable conclusion. None of the included trials reported all-cause mortality. The pooled effect indicated a reduction in systolic blood pressure (MD -6.72 mmHg, 95% CI 9.82 to -3.61, I2 = 91%, 4868 participants, low-quality evidence), diastolic blood pressure (MD -4.40 mmHg, 95% CI -6.47 to -2.34, I2 = 92%, 4701 participants, low-quality evidence), body mass index (MD -0.76 kg/m2, 95% CI 1.29 to -0.22, I2 = 80%, 2984 participants, low-quality evidence) and waist circumference (MD -3.31, 95% CI -4.77 to -1.86, I2 = 55%, 393 participants, moderate-quality evidence) in favour of multiple risk factor interventions, but there was substantial heterogeneity. There was insufficient evidence to determine the effect of these interventions on consumption of fruit or vegetables, smoking cessation, glycated haemoglobin, fasting blood sugar, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol and total cholesterol. None of the included trials reported on adverse events. AUTHORS' CONCLUSIONS: Due to the limited evidence currently available, we can draw no conclusions as to the effectiveness of multiple risk factor interventions on combined CVD events and mortality. There is some evidence that multiple risk factor interventions may lower blood pressure levels, body mass index and waist circumference in populations in LMIC settings at high risk of hypertension and diabetes. There was considerable heterogeneity between the trials, the trials were small, and at some risk of bias. Larger studies with longer follow-up periods are required to confirm whether multiple risk factor interventions lead to reduced CVD events and mortality in LMIC settings. PMID- 26272649 TI - Estimation of the optimal number of radiotherapy fractions for breast cancer: A review of the evidence. AB - BACKGROUND AND PURPOSE: There is variation in radiotherapy fractionation practice, however, there is no evidence-based benchmark for appropriate activity. An evidence-based model was constructed to estimate the optimal number of fractions for the first course of radiotherapy for breast cancer to aid in services planning and performance benchmarking. MATERIALS AND METHODS: The published breast cancer radiotherapy utilisation model was adapted. Evidence based number of fractions was added to each radiotherapy indication. The overall optimal number of fractions was calculated based on the frequency of specific clinical conditions where radiotherapy is indicated and the recommended number of fractions for each condition. Sensitivity analysis was performed to assess the impact of uncertainties on the model. RESULTS: For the entire Australian breast cancer patient population, the estimated optimal number of fractions per patient was 16.8, 14.6, 13.7 and 0.8 for ductal carcinoma in situ, early, advanced and metastatic breast cancer respectively. Overall, the optimal number of fractions per patient was 14.4 (range 14.4-18.7). CONCLUSIONS: These results allow comparison with actual practices, and workload prediction to aid in services planning. The model can be easily adapted to other countries by inserting population-specific epidemiological data, and to future changes in cancer incidence, stage distribution and fractionation recommendations. PMID- 26272650 TI - A model-based longitudinal meta-analysis of FEV1 in randomized COPD trials. AB - A model-based, longitudinal meta-analysis of the efficacy on morning trough forced expiratory volume in 1 second (FEV1 ) in chronic obstructive pulmonary disease (COPD) is presented. Literature data from 142 randomized maintenance trials were included, comprising 106,422 patients who received 19 compounds. 1982 morning trough FEV1 observations were available, each representing the mean FEV1 for a study arm at a specific timepoint. The final model for absolute FEV1 included baseline, disease progression, placebo effect, and drug effect estimates for all compounds, with interstudy variability on all model components and additional interarm variability on baseline. A dose-response relationship was identifiable for 10 of the 19 compounds. Drug-drug interactions among direct bronchodilators and the effect of concomitant background COPD treatment were included. Covariates were identified on baseline. Disease progression was proportional to the baseline FEV1 , and a mean baseline of <1.2 L resulted in a lower efficacy, in particular for antiinflammatory treatments. PMID- 26272651 TI - A dual functional peptide carrying in vitro selected catalytic and binding activities. AB - When minimal functional sequences are used, it is possible to integrate multiple functions on a single peptide chain, like a "single stroke drawing". Here a dual functional peptide was designed by combining in vitro selected catalytic and binding activities. For catalytic activity, we performed in vitro selection for a peptide aptamer binding to hemin by using ribosome display and isolated a peptide that had peroxidase activity in the presence of hemin. By combining the selected catalytic peptide with a peptide antigen, which can be recognized by an antibody, an enzyme-antibody conjugate-like peptide was obtained. This study demonstrates a successful strategy to create dual functionalized peptide chains for use in immunoassays. PMID- 26272653 TI - Activity concentrations of (137)Caesium and (210)Polonium in seafood from fishing regions of New Zealand and the dose assessment for seafood consumers. AB - A study was undertaken to determine activity concentrations for (134)Caesium, (137)Caesium and (210)Polonium in New Zealand seafood, and establish if activity concentrations varied with respect to species/ecological niche and coastal region. Thirty seafood samples were obtained from six fishing regions of New Zealand along with a further six samples of two commercially important species (hoki and arrow squid) with well-defined fisheries. (134)Caesium was not detected in any sample. (137)Caesium was detected in 47% of samples, predominantly in pelagic fish species, with most activities at a trace level. Detections of (137)Caesium were evenly distributed across all regions. Activity concentrations were consistent with those expected from the oceanic inventory representing residual fallout from global nuclear testing. (210)Polonium was detected above the minimum detectable concentration in 33 (92%) of the analysed samples. Molluscs displayed significantly elevated activity concentrations relative to all other species groups. No significant regional variation in activity concentrations were determined. Two dose assessment models for high seafood consumers were undertaken. Dose contribution from (137)Caesium was minimal and far below the dose exemption limit of 1 mSv/year. Exposure to (210)Polonium was significant in high seafood consumers at 0.44-0.77 mSv/year (5th-95th percentile). (137)Caesium is concluded to be a valuable sentinel radionuclide for monitoring anthropogenic releases, such as global fallout and reactor releases, in the marine environment. (210)Polonium is of importance as a natural radionuclide sentinel due to its high contribution to dietary committed dose in seafood consumers. PMID- 26272652 TI - Tunable terahertz fishnet metamaterials based on thin nematic liquid crystal layers for fast switching. AB - The electrically tunable properties of liquid-crystal fishnet metamaterials are theoretically investigated in the terahertz spectrum. A nematic liquid crystal layer is introduced between two fishnet metallic structures, forming a voltage controlled metamaterial cavity. Tuning of the nematic molecular orientation is shown to shift the magnetic resonance frequency of the metamaterial and its overall electromagnetic response. A shift higher than 150 GHz is predicted for common dielectric and liquid crystalline materials used in terahertz technology and for low applied voltage values. Owing to the few micron-thick liquid crystal cell, the response speed of the tunable metamaterial is calculated as orders of magnitude faster than in demonstrated liquid-crystal based non-resonant terahertz components. Such tunable metamaterial elements are proposed for the advanced control of electromagnetic wave propagation in terahertz applications. PMID- 26272655 TI - Assessment of Myocardial Remodeling Using an Elastin/Tropoelastin Specific Agent with High Field Magnetic Resonance Imaging (MRI). AB - BACKGROUND: Well-defined inflammation, proliferation, and maturation phases orchestrate the remodeling of the injured myocardium after myocardial infarction (MI) by controlling the formation of new extracellular matrix. The extracellular matrix consists mainly of collagen but also fractions of elastin. It is thought that elastin is responsible for maintaining elastic properties of the myocardium, thus reducing the risk of premature rupture. An elastin/tropoelastin-specific contrast agent (Gd-ESMA) was used to image tropoelastin and mature elastin fibers for in vivo assessment of extracellular matrix remodeling post-MI. METHODS AND RESULTS: Gd-ESMA enhancement was studied in a mouse model of myocardial infarction using a 7 T MRI scanner and results were compared to those achieved after injection of a nonspecific control contrast agent, gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). In the infarcted tissue, Gd-ESMA uptake (measured as R1 relaxation rate) steadily increased from day 3 to day 21 as a result of the synthesis of elastin/tropoelastin. R1 values were in good agreement with histological findings. A similar R1 behavior was observed in the remote myocardium. No mature cross-linked elastin was found at any time point. In contrast, Gd-DTPA uptake was only observed in the infarct with no changes in R1 values between 3 and 21 days post-MI. CONCLUSIONS: We demonstrate the feasibility of in vivo imaging of extracellular matrix remodeling post-MI using a tropoelastin/elastin binding MR contrast agent, Gd-ESMA. We found that tropoelastin is the main contributor to the increased MRI signal at late stages of MI where its augmentation in areas of infarction was in good agreement with the R1 increase. PMID- 26272654 TI - Effect of High-Calcium Diet on Coronary Artery Disease in Ossabaw Miniature Swine With Metabolic Syndrome. AB - BACKGROUND: Calcium is a shortfall essential nutrient that has been a mainstay of osteoporosis management. Recent and limited findings have prompted concern about the contribution of calcium supplementation to cardiovascular risk. A proposed mechanism is through the acceleration of coronary artery calcification. Determining causality between calcium intake and coronary artery calcification has been hindered by a lack of sensitive methodology to monitor early vascular calcium accumulation. The primary study aim was to assess the impact of high calcium intake on coronary artery calcification using innovative calcium tracer kinetic modeling in Ossabaw swine with diet-induced metabolic syndrome. Secondary end points (in vitro wire myography, histopathology, intravascular ultrasound) assessed coronary disease. METHODS AND RESULTS: Pigs (n=24; aged ~15 months) were fed an atherogenic diet with adequate calcium (0.33% by weight) or high calcium (1.90% from calcium carbonate or dairy) for 6 months. Following 5 months of feeding, all pigs were dosed intravenously with (41)Ca, a rare isotope that can be measured in serum and tissues at a sensitivity of 10(-18) mol/L by accelerator mass spectrometry. Kinetic modeling evaluated early coronary artery calcification using (41)Ca values measured in serial blood samples (collected over 27 days) and coronary artery samples obtained at sacrifice. Serum disappearance of (41)Ca and total coronary artery (41)Ca accumulation did not differ among groups. Secondary end points demonstrated no treatment differences in coronary artery disease or function. CONCLUSION: There was no detectable effect of high calcium diets (from dairy or calcium carbonate) on coronary artery calcium deposition in metabolic syndrome swine. PMID- 26272656 TI - Korean Atrial Fibrillation (AF) Network: Genetic Variants for AF Do Not Predict Ablation Success. AB - BACKGROUND: Genomewide association studies have identified several loci associated with atrial fibrillation (AF) and have been reportedly associated with response to catheter ablation for AF in patients of European ancestry; however, associations between top susceptibility loci and AF recurrence after ablation have not been examined in Asian populations. We examined whether the top single nucleotide polymorphisms (SNPs) at chromosomes 4q25 (PITX2), 16q22 (ZFHX3), and 1q21 (KCNN3) were associated with AF in a Korean population and whether these SNPs were associated with clinical outcomes after catheter ablation for AF. METHODS AND RESULTS: We determined the association between 4 SNPs and AF in 1068 AF patients who underwent catheter ablation (74.6% male, aged 57.5+/-10.9 years, 67.9% paroxysmal AF) and 1068 age- and sex-matched controls. The SNPs at the PITX2 and ZFHX3 loci, but not the KCNN3 locus, were significantly associated with AF (PITX2/rs6843082_G: odds ratio 3.41, 95% CI 2.55 to 4.55, P=1.32*10(-16); PITX2/rs2200733_T: odds ratio 2.05, 95% CI 1.66 to 2.53, P=2.20*10(-11); ZFHX3/rs2106261_A: odds ratio 2.33, 95% CI 1.87 to 2.91, P=3.75*10(-14); KCNN3/rs13376333_T: odds ratio 1.74, 95% CI 0.93 to 3.25, P=0.085). Among those patients who underwent catheter ablation for AF, none of the top AF-associated SNPs were associated with long-term clinical recurrence of AF after catheter ablation. CONCLUSIONS: SNPs at the PITX2 and ZFHX3 loci were strongly associated with AF in Korean patients. In contrast to prior reports, none of the 4 top AF susceptibility SNPs predicted clinical recurrence after catheter ablation. PMID- 26272658 TI - Optimal GHZ Paradox for Three Qubits. AB - Quatum nonlocality as a valuable resource is of vital importance in quantum information processing. The characterization of the resource has been extensively investigated mainly for pure states, while relatively less is know for mixed states. Here we prove the existence of the optimal GHZ paradox by using a novel and simple method to extract an optimal state that can saturate the tradeoff relation between quantum nonlocality and the state purity. In this paradox, the logical inequality which is formulated by the GHZ-typed event probabilities can be violated maximally by the optimal state for any fixed amount of purity (or mixedness). Moreover, the optimal state can be described as a standard GHZ state suffering flipped color noise. The maximal amount of noise that the optimal state can resist is 50%. We suggest our result to be a step toward deeper understanding of the role played by the AVN proof of quantum nonlocality as a useful physical resource. PMID- 26272657 TI - Acetabuloplasties at Open Reduction Prevent Acetabular Dysplasia in Intentionally Delayed Developmental Dysplasia of the Hip: A Case-control Study. AB - BACKGROUND: Avascular necrosis (AVN) and residual acetabular dysplasia are the two main complications of developmental dysplasia of the hip (DDH) treatment. Although early reduction of the hip may decrease the incidence of residual dysplasia, it may increase the incidence of AVN and vice versa. However, we do not know if changes in surgical technique may lead to a modification in these outcomes. QUESTIONS/PURPOSES: Does an incomplete periacetabular acetabuloplasty, as an added step to delayed open reduction, (1) diminish the risk of developing acetabular dysplasia; or (2) increase the rate of AVN compared with patients treated with open reduction alone? METHODS: We conducted a retrospective matched case-control study comparing 22 patients (27 hips) with early isolated DDH who underwent intentionally delayed open reduction and acetabuloplasty from 2004 to 2010 and followed up > 4 years (88% of the cohort) with early historic controls treated with delayed open reduction alone. Of 53 patients available for matching, 45 (85%) had enough followup (> 10 years) to be considered. They were matched one to one for age at presentation and bilaterality (fuzz 45, 0). This generated a control group of 25 patients (27 hips). The mean followup was different between the groups (p < 0.001). Residual dysplasia considered when center-edge angle < 15 degrees (6-13 years old) or < 20 degrees (>= 14 years old) or as a nonevolving acetabular index > 30 degrees and pelvic osteotomies were used as our primary outcomes. The proportion of patients with AVN was also compared. RESULTS: Patients treated with open reduction and an incomplete periacetabular acetabuloplasty were less likely to develop acetabular dysplasia and undergo pelvic osteotomies than were patients in the control group (0% [zero of 27] versus 37% [10 of 27]; odds ratio [OR], 11; 95% confidence interval [CI], 2-80; p = 0.02 and 0% [zero of 27] versus 26% [seven of 27]; OR, 8; 95% CI, 1-60; p = 0.025, respectively). With the available numbers, there was no difference in terms of the proportion of patients who developed AVN (11 of 27 [41%] both groups; OR, 1; 95% CI, 1-2; p = 1). CONCLUSIONS: The addition of an incomplete periacetabular acetabuloplasty to all hips undergoing open reduction eliminated residual acetabular dysplasia, whereas it did not appear to have deleterious effects as evidenced by the similar AVN proportion. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID- 26272659 TI - Cytotoxic and antibacterial activities of the analogues of pogostone. AB - Six new (A5-A6, A8-A11) and six known (A1-A4, A7, PO) alpha-pyrone compounds were synthesized with dehydroacetate and aldehydes in tetrahydrofuran at room temperature. And their structures were determined by (1)H-NMR, (13)C-NMR and mass spectroscopy. In the bioscreening experiments, ten compounds (A1-A5, PO, A7-A10) exhibited antibacterial activities against Staphylococcus aureus ATCC 25923 with minimum inhibitory concentration (MIC) values of 4-512 mg/L, and nine compounds (A1-A5, PO, A7-A8, A10) exhibited antibacterial activities against Methicillin resistant S. aureus (MRSA) ATCC 43300 with MIC values of 4-256 mg/L. Moreover, compound A10 showed the highest antibacterial activity against S. aureus ATCC 25923 and MRSA with MIC values of 4 mg/L, while the MIC values of Amoxicillin were 8 mg/L and >256 mg/L, respectively. Two compounds (A8 and PO) exhibited antibacterial activities against Escherichia coli ATCC 25922 with MIC values of 32-512 mg/L. However, only one compound (A8) exhibited significant antibacterial activity against Pseudomonas aeruginosa CVCC 3360 with MIC value of 256 mg/L. Moreover, A10 exhibited significant inhibition of proliferation in the four cell lines MCF-10, A549, A2780 and MFC, and showed stronger inhibitive activity of these four selected cell lines than cisplatin in the cytotoxic assay. Thus, this study suggests that pogostone analogues, especially A10, represented a kind of promising antibacterial and antineoplastic agents. PMID- 26272660 TI - Association of clusterin (CLU) variants and exfoliation syndrome: An analysis in two Caucasian studies and a meta-analysis. AB - Exfoliation syndrome (XFS) is an important risk factor for glaucoma (XFG) worldwide. LOXL1 variants are highly associated with XFS in most populations; however, the high frequency of risk alleles in normal individuals and the reversal of risk alleles in different ethnic populations suggest that other factors contribute to XFS pathogenesis. Clusterin (CLU) is an extracellular matrix chaperone that prevents protein aggregation and is highly expressed in ocular tissues affected by XFS. Studies examining common CLU variants for association with XFS have been inconsistent. The purpose of this study was to evaluate CLU variants for association with XFS in two independent datasets from the United States (222 cases and 344 controls) and Israel (92 cases and 102 controls). Seven tag SNPs that captured >95% of alleles at r(2) greater than 0.8 across the CLU genomic region were genotyped using TaqMan assays. Genotypes for an additional SNP, rs2279590, were imputed using phased haplotypes of HapMap reference CEU samples. Of the 8 CLU SNPs selected for the study, none were significantly associated with XFS in either case-control group (age and sex adjusted P > 0.14 and 0.36, respectively, in the US and Israeli datasets), or when they were meta-analyzed together (age and sex adjusted P > 0.13). Haplotype analysis using all 8 SNPs or only the promoter region SNPs also did not show significant associations of CLU with XFS in the combined US and Israeli dataset (P > 0.28). Meta-analysis of the data from this study and previous studies in Caucasian populations (1184 cases and 978 controls) resulted in statistically significant association of rs2279590 with XFS (summary OR = 1.18, 95% CI: 1.03 1.33, P = 0.01). Significant association between rs2279590 and XFS was also found in Indian populations (summary OR = 0.76, 95% CI: 0.61-0.96; P = 0.02); however, significant heterogeneity between the Caucasian and Indian populations possibly due to reversal of the risk allele precluded an overall meta-analysis for rs2279590 (Q = 0.001, I(2) = 91%). No significant association was identified for rs3087554 in either Caucasian populations (summary OR = 0.90, 95% CI: 0.77-1.05, P = 0.17) or Indian populations (summary OR = 0.89, 95% CI: 0.72-1.10, P = 0.28), or in both populations combined (1705 cases and 3713 controls; summary OR = 0.90, 95% CI: 0.79-1.01, P = 0.08). Significant heterogeneity precluded the addition of the Japanese data to the meta-analysis for rs3087554 (Q = 0.006, I(2) = 87%). Our results suggest that common CLU variants may contribute to modest XFS risk but even larger datasets are required to confirm these findings. PMID- 26272661 TI - PATRONUS1 is expressed in meiotic prophase I to regulate centromeric cohesion in Arabidopsis and shows synthetic lethality with OSD1. AB - BACKGROUND: Retention of sister centromere cohesion during meiosis I and its dissolution at meiosis II is necessary for balanced chromosome segregation and reduction of chromosome number. PATRONUS1 (PANS1) has recently been proposed to regulate centromere cohesion in Arabidopsis after meiosis I, during interkinesis. pans1 mutants lose centromere cohesion prematurely during interkinesis and segregate randomly at meiosis II. PANS1 protein interacts with components of the Anaphase Promoting Complex/Cyclosome (APC/C). RESULTS: We show here that PANS1 protein is found mainly in prophase I of meiosis, with its level declining late in prophase I during diplotene. PANS1 also shows expression in dividing tissues. We demonstrate that, in addition to the previously reported premature loss of centromere cohesion during interkinesis, pans1 mutants show partially penetrant defects in centromere cohesion during meiosis I. We also determine that pans1 shows synthetic lethality at the level of the sporophyte, with Omission of Second Division 1 (osd1), which encodes a known inhibitor of the APC/C that is required for cell cycle progression during mitosis, as well as meiosis I and II. CONCLUSIONS: Our results show that PANS1 is expressed mainly in meiosis I where it has an important function and together with previous studies indicate that PANS1 and OSD1 are part of a network linking centromere cohesion and cell cycle progression through control of APC/C activity. PMID- 26272663 TI - Editorial. PMID- 26272662 TI - Metastatic endophthalmitis combined with subretinal abscess in a patient with diabetes mellitus--a case report. AB - BACKGROUND: Endogenous endophthalmitis, extra-hepatic metastasis from liver abscess with diabetes mellitus, could lead to a devastating outcome without a prompt and appropriate management. We report a case of metastatic endophthalmitis combined with subretinal abscess with successful visual outcome after treatment. CASE PRESENTATION: A 56-year-old male patient with diabetes mellitus under poor control presented to our emergency room with fever, sore throat, cough and poor appetite for 2 weeks. Abdominal computed tomography showed a 2.2 * 2.0 cm liver abscess. During hospitalization, sudden onset of blurred vision with floaters in his left eye was noted. Meanwhile, Brain computed tomography demonstrated subdural abscess in right parietal area. With obvious vitritis, a localized subretinal abscess was also found over temporal arcade with size about four disc areas under indirect ophthalmoscopy. A pars plana vitrectomy with intravitreal injection of ceftazidime (2 mg/0.1 ml) and amikacin (0.4 mg/0.1 ml) was performed without retinectomy. The margin of the subretinal abscess became firm and the central area resolved after the operation. Finally, his vision improved to 6/6 after cataract surgery. CONCLUSIONS: Subretinal abscess is an extremely rare presentation of metastatic endophthalmitis. It is difficult to develop appropriate treatment guidelines of endophthalmitis complicated with subretinal abscess. Our experience in this case demonstrated if the size of the subretinal abscess is smaller than four disc areas, pars plana vitrectomy with intravitreal injection of antibiotics without retinectomy could be considered to avoid further retinal detachment. PMID- 26272664 TI - Intra-nucleus-accumbens SKF38393 improved the impaired acquisition of morphine conditioned place preference in depression-like rats. AB - Dopaminergic activity in the nucleus accumbens (NAc) and the globus pallidus (GP) is important for the interaction between depression and addiction, with D1- and D2-like receptors playing different roles. Here, we address the effect of depression on morphine reward and its underlying D1- and D2-like effects in the NAc and/or the GP. Novelty-seeking behaviors and the forced open-space swimming test were used to assess a depression-like state in rats that had undergone chronic mild restraint. Depression-like rats were then trained with morphine induced conditioned place preference (CPP, 3 mg/kg, 4 days), and showed impaired acquisition of the CPP compared with controls. To examine the receptor-specific dopaminergic mechanism underlying this phenomenon, we microinjected the D1-like agonist SKF38393 (1 MUg/side) or the D2-like agonist quinpirole (1 MUg/side) into the NAc or the GP. The impairment in acquisition of CPP was reversed only by injecting the D1- but not the D2-like agonist in the NAc. These results suggest that enhancement of dopaminergic transmission in the NAc (via D1-like receptors) may be effective in recovering impaired reward learning during a depression-like state. PMID- 26272665 TI - The "hot hand" revisited: A nonstationarity argument. AB - The "hot hand belief," that a basketball player would experience elevated performance for a certain period of time, during which consecutive shots are made in streaks, has been suggested to be a "cognitive illusion," because, from the basketball-shooting data, no significant evidence has been found to reject the simple binomial model. The present study raises concerns about the statistical methods used to support this claim. It is argued that nonstationarity may manifest as a residual effect when the changes in shooting accuracy are interrupted by activities such as shot selection and defense effort. Reanalyses of the field goal data from the earlier study showed that the serial correlation varied substantially between positive ("hot hand shooting") and negative ("over alternation shooting"). In addition, a nested model comparison revealed that when a player's shooting accuracy fluctuated substantially in a short period of time, it was unlikely to be detected by the binomial model. Our results suggest that paying special attention to streak patterns in the hot hand belief may be an adaptive strategy in detecting changes in the environment. PMID- 26272666 TI - Filial piety and traditional Chinese values: A study of high and mass cultures. AB - Two studies were conducted, using indigenous materials stemming from both high and mass culture to construct measures of filial piety and other traditional Chinese values. In Study 1, data were collected from a sample of 666 participants (334 men and 332 women) with a mean age of 31.2 years from Taiwan and Hong Kong. In Study 2, data were collected from university students at different times, based on two samples in Hong Kong and another two in mainland China. The major findings are: (a) Filial piety is rooted more firmly in the ideal values of high culture than in the folk values of mass culture; (b) traditional Chinese values tend to be negatively associated with socioeconomic status; (c) ideal values are held much more strongly than folk values; and (d) among university students, there has been a moderate decrease in folk values in Hong Kong; but a moderate increase in folk values and a fairly large increase in ideal values in mainland China. PMID- 26272667 TI - Differential effects of acute amphetamine and phencyclidine treatment and withdrawal from repeated amphetamine or phencyclidine treatment on social interaction and social memory in rats. AB - Although animal models based on amphetamine (AMPH) or phencyclidine (PCP) treatment have been used extensively to study the neurobiological and behavioral characteristics of schizophrenia, there are conflicting reports regarding their validity in modeling the negative symptoms and cognitive deficits of schizophrenia. The present study examined how acute AMPH or PCP treatment (Experiment 1) and withdrawal from repeated AMPH treatment (Experiment 2) or PCP treatment (Experiment 3) affects social behavior and social recognition memory in male Sprague-Dawley rats. Each subject was tested on two consecutive days. On the first day, the rats were tested four times (5 min/each) at 10-min intervals with the same partner rat (termed "AAAA" day). One day later, the rats were tested with the previous partner in the first three sessions and with a new partner rat in the final session (termed "AAAB" day). The results show that acute AMPH treatment (1.5 mg/kg, sc) significantly reduced the time spent on social interaction, but did not affect social recognition on the first day. Acute AMPH only disrupted social recognition on the second day of drug testing. In contrast, acute PCP treatment (2.0 mg/kg, sc) had no effect on time spent on social interaction, but did significantly disrupt social recognition on both days. Withdrawal from repeated AMPH (3.0 mg/kg/day for 7 days, ip) or PCP (5.0 mg/kg/twice daily for 7 days, ip) treatment did not affect social interaction or social recognition, indicating a lack of long-term detrimental effect of repeated AMPH or PCP treatment. These results suggest that acute AMPH treatment at a low dose (1.5 mg/kg) may be useful in modeling social withdrawal symptoms of schizophrenia, whereas acute PCP treatment at a similar dose range (2.0 mg/kg) may be useful in modeling the social cognitive deficit of schizophrenia. PMID- 26272669 TI - [Not Available]. PMID- 26272668 TI - Derivation of a fifteen gene prognostic panel for six cancers. AB - The hallmarks of cancer deem biological pathways and molecules to be conserved. This approach may be useful for deriving a prognostic gene signature. Weighted Gene Co-expression Network Analysis of gene expression datasets in eleven cancer types identified modules of highly correlated genes and interactive networks conserved across glioblastoma, breast, ovary, colon, rectal and lung cancers, from which a universal classifier for tumor stratification was extracted. Specific conserved gene modules were validated across different microarray platforms and datasets. Strikingly, preserved genes within these modules defined regulatory networks associated with immune regulation, cell differentiation, metastases, cell migration, metastases, oncogenic transformation, and resistance to apoptosis and senescence, with AIF1 and PRRX1 being suggested to be master regulators governing these biological processes. A universal classifier from these conserved networks enabled execution of common set of principles across different cancers that revealed distinct, differential correlation of biological functions with patient survival in a cancer-specific manner. Correlation analysis further identified a panel of 15 risk genes with potential prognostic value, termed as the GBOCRL-IIPr panel [(GBM-Breast-Ovary-Colon-Rectal-Lung)-Immune Invasion-Prognosis], that surprisingly, were not amongst the master regulators or important network hubs. This panel may now be integrated in predicting patient outcomes in the six cancers. PMID- 26272670 TI - [What influences end-of-life decisions? Results of a representative German survey]. AB - BACKGROUND: Because of demographic changes of an aging society, palliative care is becoming increasingly important. It is therefore necessary to evaluate preferences at the end of life at an early stage to meet the needs and requests of future patients. OBJECTIVES: The aim of this study was to find out preferences in a theoretical scenario ("If you developed a serious medical condition such as cancer and you had less than a year to live...") regarding the desired involvement in decision-making at the end of life and the preferred place of death. MATERIALS AND METHODS: As part of the international PRISMA project, a representative telephone survey was carried out in Germany. RESULTS: A total of 1,363 Germans took part in the survey (response rate 29.0 %, 47.1 +/- 15.7 years, 42 % male). 90.8 % wanted to make their own decisions with regard to end-of-life care, which was most important for people with higher education. 83.3 % wanted to predetermine decisions by means of an advance directive in case they are no longer able to make them at the time. This was again more important for individuals with higher education and for older subjects (>= 65 years). The preferred place of death was their own home (63.3 %), and the least preferred place for death was in hospital in 48.2 %. In particular, women did not want to die in a hospital. CONCLUSION: These results should be considered when planning health care structures to meet the wishes of people at the end of their life, in particular to strengthen the importance of patient provision and the desire for their own home to be the preferred place to die. PMID- 26272671 TI - High dose therapy and autologous hematopoietic stem cell transplantation in septuagenarians with non-Hodgkin lymphoma: Feasible, but for which patients? PMID- 26272672 TI - Construction and characterization of an infectious clone of coxsackievirus A6 that showed high virulence in neonatal mice. AB - Atypical hand, foot, and mouth disease (aHFMD) outbreaks have been frequently reported worldwide in recent years. It is believed that coxsackievirus A6 (CA6) is the major pathogen for aHFMD. Studies regarding CA6 infection are limited and the genetic mechanism for the high pathogenicity of some new CA6 variants is still unclear. Infectious clones are powerful tools for studying the genetic mechanisms of RNA viruses. In this study, we describe the construction of a full length cDNA clone of CA6 strain TW-2007-00141. The whole genome of CA6 was amplified in a single step and ligated into a plasmid vector through an efficient cloning method, Gibson assembly. The whole genome sequence of CA6 strain TW-2007 00141 was determined and phylogenetic analysis indicated that it shared a high degree of similarity (>=94%) with the CA6 strains found in Taiwan in 2009. The infectious clone of CA6 viruses were recovered by transfection into 293FT cells and showed similar biological properties to the parental virus. Viral particles were purified by CsCl isopycnic centrifugation, and two types of viral particles were observed under transmission electron microscopy. The rescued virus showed high virulence in one-day-old suckling mice. This clone may be useful for establishing animal models for the evaluation of CA6 vaccine efficiency in future. PMID- 26272673 TI - Identification of CD8 T cell epitopes in VP2 and NS1 proteins of African horse sickness virus in IFNAR(-/-) mice. AB - African horse sickness virus (AHSV) is an Orbivirus of the family Reoviridae that causes severe pathology in equids. Previous work in our laboratory showed the presence of AHSV-specific CD8(+) T cells in mice immunized with recombinant Modified Vaccinia Ankara (rMVA) expressing VP2 and NS1 proteins. In the present work, we selected potential CD8 T cell epitopes (MHC-class I binding peptides) for the 129 mouse strain from the VP2 and NS1 proteins of AHSV-4, using a combination of four epitope prediction algorithms (SYFPEITHI, BYMAS, NetMHC I and NetMHCpan). ELISPOT and Intracellular Cytokine Staining (ICS) analysis showed that the VP2-720 (MSLLNFGAV), VP2-1044 (YTFGNKFLL), and NS1-83 (CVIKNADYV) peptides elicited IFN-gamma production in splenocytes of MVA-VP2 and MVA-NS1 immunized mice and were identified as CD8(+) T cell epitopes. In addition, these three MHC-class I-binding peptides induced the expression of CD107a in CD8(+) T cells, an indirect marker of cytotoxic activity. Importantly, VP2-1044 and NS1-83 epitopes are conserved among all nine AHSV serotypes. These data demonstrate the activation of AHSV specific T-cell epitopes during vaccination with rMVAs expressing VP2 and NS1. Furthermore, the characterization of these CD8(+) T-cell epitopes provides information useful for the design of novel marker multiserotype vaccines against AHSV. PMID- 26272674 TI - Primary hepatic neuroendocrine tumors: comparing CT and MRI features with pathology. AB - BACKGROUND: Primary hepatic neuroendocrine tumors (PHNET) are extremely rare and difficult to distinguish from primary and metastatic liver cancers since PHNETs blood supply comes from the liver artery. This study aims to investigate CT and MR imaging findings of primary hepatic neuroendocrine tumor (PHNET) and correlation with the 2010 WHO pathological classification. METHODS: We examined CT and MRI scans from 29 patients who were diagnosed with PHNET and correlated the data with the 2010 WHO classification of neuroendocrine tumors. RESULTS: According to the 2010 WHO classification system, PHNETs are divided into three grades based on histological criteria. Grade 1 tumors are singular, solid nodules with enhancement at the arterial phase on CT and MRI scans. In grade 1 tumors, the dynamic-contrast enhancement curve shows rapid wash-in in the arterial phase. Grade 2 tumors can have a singular or multiple distribution pattern, necrosis, and nodule or marginal ring-like enhancements. Grade 3 tumors have multiple lesions, internal necrosis, and evidence of hemorrhage. Portal venous tumor thrombus was seen in one case. As tumor grades increase, the capsule begins to lose integrity and tumor apparent diffusion coefficient (ADC) values decrease(grade 1: 1.39 +/- 0.20* 10(-3) mm(2)/s versus grade 2: 1.26 +/- 0.23* 10(-3) mm(2)/s versus grade 3: 1.14 +/- 0.17* 10(-3) mm(2)/s). CONCLUSION: CT and MRI can reflect tumor grade and pathological features of PHNETs, which are helpful in accurately diagnosing PHNETs. PMID- 26272675 TI - The Relationship Between Subthreshold Autistic Traits, Ambiguous Figure Perception and Divergent Thinking. AB - This research investigates the paradox of creativity in autism. That is, whether people with subclinical autistic traits have cognitive styles conducive to creativity or whether they are disadvantaged by the implied cognitive and behavioural rigidity of the autism phenotype. The relationship between divergent thinking (a cognitive component of creativity), perception of ambiguous figures, and self-reported autistic traits was evaluated in 312 individuals in a non clinical sample. High levels of autistic traits were significantly associated with lower fluency scores on the divergent thinking tasks. However autistic traits were associated with high numbers of unusual responses on the divergent thinking tasks. Generation of novel ideas is a prerequisite for creative problem solving and may be an adaptive advantage associated with autistic traits. PMID- 26272676 TI - Erratum to: defining treatment response and symptom remission for anxiety disorders in pediatric autism spectrum disorders using the Pediatric Anxiety Rating Scale. PMID- 26272677 TI - Association between periodontitis and medical expenditure in older adults: A 33 month follow-up study. AB - AIM: Along with rapid aging, medical expenditure for older adults has been increasing in Japan. Research has shown that periodontitis is a useful predictor for excess medical expenditure; however, limited information is available on the elderly population after adequately considering confounding factors. The aim of the present study was to evaluate the association between periodontitis and long term medical expenditure in elderly Japanese. METHODS: Baseline health and periodontal examinations were carried out in June 2008. Japanese adults (n = 245) aged 80 years were classified into quartiles based on periodontal inflamed surface area (PISA), which quantifies the degree of periodontal inflammation. Medical care use and costs were monitored by assessment of the National Health Insurance claim files from the baseline survey through the end of February 2011. Multivariable analysis of the differences in medical expenditure among PISA quartiles was carried out using linear regression with robust standard errors. RESULTS: The participants in the fourth (with the largest PISA) and third quartiles had significantly higher inpatient medical expenditure compared with those of the first quartile (P < 0.01 and = 0.04, respectively). Participants in the fourth quartile had significantly higher total medical expenditure (P < 0.01) compared with the first quartile. A trend was observed of higher inpatient and total medical expenditure with increasing PISA. CONCLUSIONS: A significant association was found between periodontitis and future increase in medical expenditure, suggesting that periodontitis might be a modifiable factor for the reduction of excess medical expenditure among elderly Japanese. Geriatr Gerontol Int 2016; 16: 856-864. PMID- 26272678 TI - Physical activity and sedentary behaviour of adults with mental illness. AB - OBJECTIVES: To assess physical activity (PA) and sedentary behaviour (SB) in non institutionalised adults with mental illness, using a combination of self-report and objective measures. DESIGN: Cross-sectional METHODS: Participants completed PA questionnaires (time spent walking for transport, walking for recreation, gardening, vigorous-, and moderate-intensity activities), and SB questionnaires (time spent sitting for TV, travel, work, computer use, and reclining). Participants also wore an accelerometer for 7 days. Accelerometry estimates of time spent in SB, light activity, and moderate-to-vigorous activity (MVPA), bout durations, and, breaks in sedentary time, were calculated. RESULTS: 142 participants completed the questionnaires. The median time spent in self-reported MVPA and SB was 4.5h/week and 10.7h/day, respectively. Walking for transport, and sitting to watch TV, contributed most to self-report estimates; time spent reclining was an important contributor to SB. Ninety-nine participants completed the accelerometry. The median time spent in accelerometer-derived MVPA and SB was 26min/day and 9.2h/day respectively; 7% of MVPA time was in bouts of 10min or more, and 34% of SB time was in bouts of over 20min. CONCLUSIONS: A high proportion of participants reported activity levels consistent with physical activity guidelines; however, a small proportion of activity was accumulated in bouts of 10min or more. Participants also had high levels of SB, about one-third of which was accumulated in bouts over 20min. PA and SB interventions for this group could target increasing recreational walking, and reducing television time. PMID- 26272679 TI - Loading of osseointegrated implants for bone conduction hearing at 3 weeks: 3 year stability, survival, and tolerability. AB - The objective of this study was to ascertain the long-term safety of loading osseointegrated implants for bone conduction hearing 3 weeks post-surgery. Thirty consecutive adult patients were implanted with the Baha BI300 (Cochlear Bone Anchored Solutions) in our tertiary referral center. Implants were loaded with the sound processor 3 weeks post-surgery. Follow-up examinations were performed at 10 days; 3, 4, 6, 8, and 12 weeks; 6 months; and 1, 2, and 3 years after implant surgery. At each follow-up visit, implant stability quotient (ISQ) values were recorded by means of resonance frequency analysis, and soft tissue status was evaluated according to Holgers' classification. ISQ trends, implant survival, and soft tissue reactions were compared to a population of 52 patients with the same type of implants loaded from 6 weeks post-surgery as part of another study. Subjective benefit was measured by means of the Glasgow Benefit Inventory (GBI). After an initial dip in ISQ at 10 days after implantation, a gradually increasing trend in ISQ was found until 6 months in both populations, after which ISQ values remained above baseline values. Implant survival was 97 % in the study population and 96 % in the comparison population. Clinically relevant soft tissue reactions were found in 0.9 % (study population) and 1.7 % (comparison population) of all visits. Patients reported subjective benefit; the mean GBI score was 22.8. In conclusion, loading these implants at 3 weeks post-surgery is safe based on the current study, as long-term results show high ISQ values and good implant survival and tolerability. PMID- 26272680 TI - A flow cytometer-based method to simultaneously assess activity and selectivity of compounds against the intracellular forms of Trypanosoma cruzi. AB - Chagas disease is a major unsolved health issue in Latin America and an emerging threat worldwide. New drugs are urgently needed for chemotherapy as those available (benznidazole and nifurtimox) have variable efficacy and elevated toxicity. Efforts are actually oriented to improve tools and technologies (e.g. transgenic parasites, flow cytometry or image-based systems) for the screening of large numbers of candidate compounds for their activity against Trypanosoma cruzi (T. cruzi). Methods that test drug efficacy and selectivity in the same assay are suitable to accelerate the process of drug discovery. Here, we developed a GFP expressing T. cruzi from a moderate virulence stock and confirmed that the transgenic parasite retained the biological characteristics of the parental strain. With this tool, we established a flow cytometer-based method to simultaneously test drug activity against intracellular amastigotes and toxicity to the host cell. This one-step procedure allows determining the selectivity index of the tested compound in a sensitive and accurate manner even with low infection rates. This method can provide additional information on the interactions between drug, parasites and host cell and could be adapted to other trypanosomatids and protozoa with intracellular multiplication. PMID- 26272683 TI - Validation of potential candidate biomarkers of drug-induced nephrotoxicity and allodynia in medication-overuse headache. AB - BACKGROUND: Medication-overuse headache (MOH) is a chronic disorder that results from the overuse of analgesics drugs, triptans or other acute headache compounds. Although the exact mechanisms underlying MOH remain still unknown, several studies suggest that it may be associated with development of "central sensitization", which may cause cutaneous allodynia (CA). Furthermore, the epidemiology of drug-induced disorders suggests that medication overuse could lead to nephrotoxicity. The aim of this work was to confirm and validate the results obtained from previous proteomics studies, in which we analyzed the urinary proteome of MOH patients in comparison with healthy non-abusers individuals. METHODS: MOH patients were divided into groups on the basis of the drug abused: triptans, non-steroidal anti-inflammatory drugs (NSAIDs) and mixtures, (mainly containing indomethacin, paracetamol and, in some cases, caffeine). Healthy subjects, with a history of normal renal function, were used as controls. In this study, four proteins that were found differentially expressed in urine, and, on the basis of the literature review, resulted related to kidney diseases, were verified by Western Blot and Enzyme-linked Immunosorbent Assay (ELISA); Prostaglandin-H2 D-synthase (PTGDS), uromodulin (UROM), alpha-1 microglobulin (AMBP) and cystatin-C (CYSC). RESULTS: Western blot analysis allowed to validate our previous proteomics data, confirming that all MOH patients groups show a significant over-excretion of urinary PTGDS, UROM, AMBP and CYSC (excluding triptans group for this latter), in comparison with controls. Moreover, the expression of PTGDS was further evaluated by ELISA. Also by this assay, a significant increase of PTGDS was observed in all MOH abusers, according to 2-DE and Western blot results. CONCLUSIONS: In this study, we confirmed previous findings concerning urinary proteins alterations in MOH patients, identified and demonstrated the over-expression of PTGDS, UROM, AMBP, and CYSC, particularly in NSAIDs and mixtures abusers. Over-expression of these proteins have been related to renal dysfunction and probably, PTGDS, to the development of CA. The detection and confirmation of this proteins pattern represent a promising tool for a better understanding of potential nephrotoxicity induced by drugs overuse and may enhance awareness related to the MOH-associated risks, even in absence of clinical symptoms. PMID- 26272681 TI - Migraine and restless legs syndrome are associated in adults under age fifty but not in adults over fifty: a population-based study. AB - BACKGROUND: Recent studies have shown an association between migraine and restless legs syndrome (RLS). However, migraine prevalence peaks from the 20s to 40s whereas RLS prevalence peaks after the 50s. Despite this, reports on how migraine and RLS may be associated by age is limited. Therefore, the purpose of this study is to investigate the comorbidity between migraine and RLS according to age. METHODS: We selected a stratified random population sample of Koreans aged 19 to 69 years and evaluated them with a 60-item semi-structured interview designed to identify RLS, headache type, and clinical characteristics of migraine. To assess the association between migraine and RLS according to age, we divided participants into 5 age groups (19-29, 30-39, 40-49, 50-59, and 60-69 years) and analysed each group. RESULTS: Subjects with migraine showed an increased RLS prevalence in the 19-29 (Odds ratio [OR] = 6.6, 95 % confidence interval [CI] = 1.2-36.8) and 40-49 (OR = 6.7, 95 % CI = 1.5-33.5) age groups compared to non-headache controls but failed to showed a significant association in the 50-59 (OR = 1.1, 95 % CI = 0.2-5.6) and 60-69 (OR = 0.4, 95 % CI = 0.1 4.0) age groups. Migraineurs with 1-10 (12.5 %, OR = 2.0, 95 % CI = 1.3-3.2, p = 0.003) and >10 (12.5 %, OR = 2.5, 95 % CI = 1.0-5.6, p = 0.038) attacks per month showed an increased RLS prevalence compared to migraineurs with <1 attack per month (2.1 %). Subjects with non-migraine headaches showed an increased odds for RLS (OR = 1.8, 95 % CI = 1.3-2.7) compared to non-headache controls. There was no significant difference (9.1 % vs. 6.9 %, p = 0.339) in the RLS prevalence between migraineurs and non-migraine headache subjects. CONCLUSIONS: Our results suggest that migraine and RLS are differently associated according to age. PMID- 26272682 TI - A study of cochlear and auditory pathways in patients with tension-type headache. AB - BACKGROUND: The purpose of this study was to systematically evaluate the function of cochlear and auditory pathways in patients suffering from tension-type headache (TTH) using various audiological methods. METHODS: Twenty-three TTH patients (46 ears) and 26 healthy controls (52 ears) were included, and routine diagnostic audiometry, extended high-frequency audiometry, acoustic reflex (ASR), transient evoked otoacoustic emissions (TEOAEs), distortion product otoacoustic emissions (DPOAEs) and suppression TEOAEs were tested. RESULTS: The TTH group showed higher thresholds (P < 0.05) for both pure tone and extended high frequency audiometry at all frequencies except for 9, 14 and 16 kHz. All ASR thresholds were significantly higher (P < 0.05) in the TTH group compared with the controls, except for the ipsilateral reflex at 1 kHz, but the threshold differences between the ASR and the corresponding pure tone audiometry did not differ (P > 0.05). For the DPOAEs, the detected rates were lower (P < 0.05) in the TTH group compared with the controls at 4 and 6 kHz, and the amplitudes and signal to noise ratio (S/N) were not significantly different between groups. No differences in the TEOAEs (P > 0.05) were observed for the detected rates, amplitudes, S/Ns or contralateral suppression, except for the S/Ns of the 0.5-1 kHz TEOAE responses, which were significantly higher (P < 0.05) in the TTH group. CONCLUSIONS: The results of our study indicate that subclinical changes in cochlear function are associated with TTH. PMID- 26272684 TI - Evaluation of ADMA-DDAH-NOS axis in specific brain areas following nitroglycerin administration: study in an animal model of migraine. AB - BACKGROUND: Nitric oxide (NO) is known to play a key role in migraine pathogenesis, but modulation of NO synthesis has failed so far to show efficacy in migraine treatment. Asymmetric dimethylarginine (ADMA) is a NO synthase (NOS) inhibitor, whose levels are regulated by dimethylarginine dimethylaminohydrolase (DDAH). Systemic administration of nitroglycerin (or glyceryl trinitrate, GTN) is a NO donor that consistently induces spontaneous-like headache attacks in migraneurs. GTN administration induces an increase in neuronal NOS (nNOS) that is simultaneous with a hyperalgesic condition. GTN administration has been used for years as an experimental animal model of migraine. In order to gain further insights in the precise mechanisms involved in the relationships between NO synthesis and migraine, we analyzed changes induced by GTN administration in ADMA levels, DDHA-1 mRNA expression and the expression of neuronal and endothelial NOS (nNOS and eNOS) in the brain. We also evaluated ADMA levels in the serum. METHODS: Male Sprague-Dawley rats were injected with GTN (10 mg/kg, i.p.) or vehicle and sacrificed 4 h later. Brain areas known to be activated by GTN administration were dissected out and utilized for the evaluation of nNOS and eNOS expression by means of western blotting. Cerebral and serum ADMA levels were measured by means of ELISA immunoassay. Cerebral DDAH-1 mRNA expression was measured by means of RT-PCR. Comparisons between experimental groups were performed using the Mann Whitney test. RESULTS: ADMA levels and nNOS expression increased in the hypothalamus and medulla following GTN administration. Conversely, a significant decrease in DDAH-1 mRNA expression was observed in the same areas. By contrast, no significant change was reported in eNOS expression. GTN administration did not induce any significant change in serum levels of ADMA. CONCLUSION: The present data suggest that ADMA accumulates in the brain after GTN administration via the inhibition of DDAH-1. This latter may represent a compensatory response to the excessive local availability of NO, released directly by GTN or synthetized by nNOS. These findings prompt an additional mediator (ADMA) in the modulation of NO axis following GTN administration and offer new insights in the pathophysiology of migraine. PMID- 26272686 TI - Expression of multiple formins in adult tissues and during developmental stages of mouse brain. AB - Formins are highly conserved heterogeneous family of proteins with several isoforms having significant contribution in multiple cellular functions. Formins play crucial role in remodelling of actin cytoskeleton and thus play important role in cell motility. Formins are also involved in many cellular activities like determining cell polarity, cytokinesis and morphogenesis. Formins are multi domain protein with characteristic homodimeric formin homology 2 (FH2) domain. It nucleates the actin filaments and its activity is regulated by the presence of characteristic formin homology 1 (FH1) domain. In higher mammals like human and mouse fifteen different formin isoforms are present. However the function and expression pattern of each and every formin in different adult tissues are not well characterized. Here we have found that multiple formins are expressing in each adult tissue of mouse, irrespective of their origin from the germ layer. Formins are also expressing from early stage of development to the adulthood in brain. The expression of many formins in a single tissue of adult mouse indicates that regulation of actin cytoskeleton dynamics by formins may be crucial for physiological processes like wound healing, tissue repairing, exocytosis, endocytosis, synapse formation and maintenance. Expression of FMNL2 and Fhdc1 are high in adult mouse brain as compare to embryonic stages. Higher expression of FMNL2 and Fhdc1 indicates that FMNL2 and Fhdc1 might be very important for the adult brain functions. PMID- 26272685 TI - Comparative analysis of polymers for short interfering RNA delivery in vascular smooth muscle cells. AB - The use of short interfering RNA (siRNA) to degrade messenger RNA in the cell cytoplasm and transiently attenuate intracellular proteins shows promise in the inhibition of vascular pathogenesis. However, a critical obstacle for therapeutic application is a safe and effective delivery system. Biodegradable polymers are promising alternative molecular carriers for genetic material. Here, we aim to perform a comparative analysis of poly(B-amino ester) (PBAE) and polyethylenimine (PEI) polymers in their efficacy for vascular smooth muscle cell transfection using siRNA against the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) housekeeping gene as our test target. METHODS: Human aortic smooth muscle cells (HASMC) were transfected in vitro with polymers conjugated to GAPDH or negative control (NC) siRNAs. Increasing siRNA:polymer ratios were tested for optimal transfection efficiency. DharmaFECT2 chemical transfection complexes were used for comparative analysis. Live/dead dual stain was used to measure cell viability, and GAPDH gene silencing was measured by quantitative polymerase chain reaction normalized to 18S. RESULTS: The highest rate of PEI-mediated silencing was achieved with a 9MUL polymer:220 pmol/mL siRNA conjugate (16 +/- 2% expression versus NC; n = 6). Comparable PBAE-mediated silencing could be achieved with a 1.95MUL polymer:100 pmol/mL siRNA conjugate (10 +/- 1% expression versus NC; n = 5). Transfection using PEIs resulted in silencing equivalent to other methods but with less efficiency and increased cell toxicity at 24h polymer exposure. Decreasing PEI exposure time to 4 h resulted in similar silencing efficacy (21 +/- 9% expression versus NC, n = 6) with an improved toxicity profile. CONCLUSIONS: Polymeric bioconjugates transfected HASMCs in a manner similar to chemical complexes, with comparable cell toxicity and silencing efficiency. PEI bioconjugates demonstrated silencing equivalent to PBAE bioconjugates, although less efficient in terms of required polymer concentrations. Given the cost-to-benefit difference between the assayed polymers, and PEI's ability to transfect HASMCs within a short duration of exposure with an improved toxicity profile, this study shows that PEI bioconjugates are a potential transfection agent for vascular tissue. Future studies will expand on this method of gene therapy to validate delivery of gene specific inhibitors aimed at attenuating smooth muscle cell proliferation, adhesion, and migration. These studies will lay the framework for our future experimental plans to expand on this method of gene therapy for in vivo transfection in animal models of vascular disease. PMID- 26272687 TI - Comparison of Effectiveness of Laminaria versus Vaginal Misoprostol for Cervical Preparation Before Operative Hysteroscopy in Women of Reproductive Age: A Prospective Randomized Trial. AB - STUDY OBJECTIVE: To compare the effectiveness and safety of intracervical laminaria dilator versus intravaginal misoprostol administered before surgery to facilitate cervical dilation before operative hysteroscopy. DESIGN: A prospective randomized study (Canadian Task Force classification 1). SETTING: A university hospital. PATIENTS: A total of 150 women were assigned at random to the following groups: laminaria dilation (n = 50), misoprostol dilation (n = 50), and mechanical dilation (n = 50). INTERVENTIONS: Hysteroscopic surgery of intrauterine lesions. MEASUREMENTS AND MAIN RESULTS: In this study, 150 women were assigned at random to receive cervical priming with an intracervical laminaria dilator, 200 MUg of intravaginal misoprostol, or a mechanical dilator before operative hysteroscopy. Cervical response, surgical outcome, and complications of operative hysteroscopy were assessed. Visual analog scale (VAS) pain scores were recorded in the misoprostol and laminaria dilation groups. Demographic variables of the study groups were comparable (p = .278-.988). The duration of cervical pretreatment was similar with the intracervical laminaria dilator and intravaginal misoprostol (p = .803); however, intravaginal misoprostol was associated with more adverse effects (p = .031). Compared with the misoprostol dilation group, in which all patients required additional cervical dilation, notably fewer patients in the laminaria dilation group required additional cervical dilation after cervical preparation (p = .001). VAS pain scores were significantly higher in the laminaria dilation group, however (p = .001). CONCLUSION: Cervical priming with an intracervical laminaria dilator before operative hysteroscopy reduces the need for cervical dilation and better facilitates hysteroscopic surgery compared with intravaginal misoprostol. Oral analgesic use may be required before the use of this device. PMID- 26272688 TI - Robotic Versus Laparoscopic Hysterectomy for Benign Disease: A Systematic Review and Meta-Analysis of Randomized Trials. AB - We conducted a systematic review and meta-analysis to assess the safety and effectiveness of robotic vs laparoscopic hysterectomy in women with benign uterine disease, as determined by randomized studies. We searched MEDLINE, EMBASE, the Cochrane Library, ClinicalTrials.gov, and Controlled-Trials.com from study inception to October 9, 2014, using the intersection of the themes "robotic" and "hysterectomy." We included only randomized and quasi-randomized controlled trials of robotic vs laparoscopic hysterectomy in women for benign disease. Four trials met our inclusion criteria and were included in the analyses. We extracted data, and assessed the studies for methodological quality in duplicate. For meta-analysis, we used random effects to calculate pooled risk ratios (RRs) and weighted mean differences. For our primary outcome, we used a modified version of the Expanded Accordion Severity Grading System to classify perioperative complications. We identified 41 complications among 326 patients. Comparing robotic and laparoscopic hysterectomy, revealed no statistically significant differences in the rate of class 1 and 2 complications (RR, 0.66; 95% confidence interval [CI], 0.23-1.89) or in the rate of class 3 and 4 complications (RR, 0.99; 95% CI, 0.22-4.40). Analyses of secondary outcomes were limited owing to heterogeneity, but showed no significant benefit of the robotic technique over the laparoscopic technique in terms of length of hospital stay (weighted mean difference, -0.39 day; 95% CI, -0.92 to 0.14 day), total operating time (weighted mean difference, 9.0 minutes; 95% CI, -31.27 to 47.26 minutes), conversions to laparotomy, or blood loss. Outcomes of cost, pain, and quality of life were reported inconsistently and were not amenable to pooling. Current evidence demonstrates neither statistically significant nor clinically meaningful differences in surgical outcomes between robotic and laparoscopic hysterectomy for benign disease. The role of robotic surgery in benign gynecology remains unclear. PMID- 26272690 TI - Use of Hormone Testing for the Diagnosis and Evaluation of Male Hypogonadism and Monitoring of Testosterone Therapy: Application of Hormone Testing Guideline Recommendations in Clinical Practice. AB - INTRODUCTION: Clinical practice guidelines recommend that testosterone (T) levels be measured on >=2 occasions to confirm a diagnosis of hypogonadism, gonadotropins be measured to determine whether hypogonadism is primary or secondary, and T levels be measured to monitor the adequacy of T therapy. However, it is not known whether hormone testing as recommended by guidelines is routinely performed in real-world clinical practice. AIM: The aim of this study was to assess the use of hormone testing for the diagnosis and evaluation of hypogonadism and monitoring of T therapy in clinical practice. METHODS: In this retrospective cohort study of the Truven Health Marketscan((r)) Commercial and Medicare Supplemental Insurance Databases during 2010-2012, 63,534 men over 18 years old who received T therapy and had continuous medical benefit enrollment for 1 year prior to and 6 months after T therapy initiation were included in this analysis. MAIN OUTCOME MEASURES: Proportion of patients who received >=2, 1, or no T-level determinations prior to or following T therapy initiation. RESULTS: Seventy-one percent of hypogonadal men had T measured at least once and 40% had >= 2 tests, but only 12% of men had luteinizing hormone and/or follicle stimulating hormone levels measured prior to T therapy initiation. Following T therapy initiation, 46% had >=1 follow-up T measurements. CONCLUSIONS: Appropriate use of T and gonadotropin levels in clinical practice as recommended by guidelines is suboptimal, increasing the possibility of overdiagnosis of male hypogonadism, underdiagnosis of secondary hypogonadism, and inappropriate T therapy use and management. Further investigation is needed into reasons for nonadherence to guidelines for appropriate hormone testing to inform future quality improvement efforts. PMID- 26272689 TI - Phytoecdysteroids as modulators of the Toxoplasma gondii growth rate in human and mouse cells. AB - BACKGROUND: Searching for new effective drugs against human and animal toxoplasmosis we decided to test the anti-Toxoplasma potential of phytoecdysteroids (alpha-ecdysone and 20-hydroxyecdysone) characterized by the pleiotropic activity on mammalian organisms including the enhancement of host's anti-parasitic defence. This objective was accomplished by the in vitro evaluation of T. gondii growth in phytoecdysteroid-treated immunocompetent cells of selected hosts: humans and two strains of inbred mice with genetically determined different susceptibility to toxoplasmosis. METHODS: Peripheral mononuclear blood cells were isolated from Toxoplasma-positive and Toxoplasma negative women (N = 43) and men (N = 21). Non-infected mice (C57BL/6, N = 10 and BALB/c, N = 14) and mice (BALB/c, N = 10) challenged intraperitoneally with 5 tissue cysts of the T. gondii DX strain were also used in this study as a source of splenocytes. The effects of phytoecdysteroids on the viability of human PBMC and mouse splenocytes were evaluated using the MTT assay. The influence of phytoecdysteroids on PBMCs, splenocytes and T. gondii proliferation was measured using radioactivity tests (the level of 3[H] uracil incorporation by toxoplasms or 3[H] thymidine by PBMCs and splenocytes), which was confirmed by quantitative Real-Time PCR. Statistical analysis was performed using SigmaStat 3.5 (Systat Software GmbH). The best-fit IC50 curves were plotted using GraphPad Prism 6.0 (GraphPad Software, Inc.). RESULTS: Our results showed that phytoecdysteroids promote the multiplication of Toxoplasma in cultures of human or murine immune cells, in contrast to another apicomplexan parasite, Babesia gibsoni. Additionally, the tested phytoecdysteroids did not stimulate the in vitro secretion of the essential protective cytokines (IFN-gamma, IL-2 and IL-10), neither by human nor by murine immune cells involved in an effective intracellular killing of the parasite. CONCLUSIONS: Judging by the effect of phytoecdysteroids on the T. gondii proliferation, demonstrated for the first time in this study, it seems that these compounds should not be taken into consideration as potential medications to treat toxoplasmosis. Phytoecdysteroids included in the food are most likely not harmful for human or animal health but certain nutrients containing ecdysteroids at high concentrations could promote T. gondii proliferation in chronically infected and immunocompromised individuals. In order to assess the real impact of ecdysteroids on the course of natural T. gondii invasion, in vivo research should be undertaken because it cannot be ruled out that the in vivo effect will be different than the in vitro one. However, taking into account the possible stimulating effect of ecdysteroids on some opportunistic parasites (such as Toxoplasma or Strongyloides) further studies are necessary and should focus on the mechanisms of their action, which directly or indirectly enhance the parasite growth. Since ecdysteroids are considered as potential drugs, it is essential to determine their effect on various parasitic pathogens, which may infect the host at the same time, especially in immunocompromised individuals. PMID- 26272691 TI - Aberrant expressions of c-KIT and DOG-1 in mucinous and nonmucinous colorectal carcinomas and relation to clinicopathologic features and prognosis. AB - c-KIT and DOG-1 are 2 highly expressed proteins in gastrointestinal stromal tumors. Few studies had investigated c-KIT, but not DOG-1, expression in colorectal carcinoma (CRC). This study aims to investigate expressions of c-KIT and DOG-1 in colorectal mucinous carcinoma and nonmucinous carcinoma using manual tissue microarray technique. In this work, we studied tumor tissue specimens from 150 patients with colorectal mucinous (MA) and nonmucinous adenocarcinoma (NMA). High-density manual tissue microarrays were constructed using modified mechanical pencil tip technique, and immunohistochemistry for c-KIT and DOG-1 was done. We found that aberrant c-KIT expression was detected in 12 cases (8%); 6 cases (4%) showed strong expression. Aberrant DOG-1 expression was detected in 15 cases (10%); among them, only 4 cases (2.7%) showed strong expression. Nonmucinous adenocarcinoma showed a significantly high expression of c-KIT, but not DOG-1, than MA. Aberrant c-KIT and DOG-1 expressions were significantly unrelated but were associated with excessive microscopic abscess formation. Neither c-KIT nor DOG-1 expression showed a significant impact on disease-free survival or overall survival. In conclusion, aberrant c-KIT and DOG-1 expressions in CRC are rare events, either in NMA or MA. Nonmucinous adenocarcinoma showed a significantly higher expression of c-KIT, but not DOG-1, than MA. The expressions of both in CRC are significantly unrelated but are associated with microscopic abscess formation. Neither c-KIT nor DOG-1 expression showed a significant impact on disease-free survival or overall survival. So, c-KIT and DOG-1 immunostaining is not a cost-effective method of identifying patients with CRC who may benefit from treatment with tyrosine kinase inhibitors. PMID- 26272692 TI - A statistical evaluation of the safety factor and species sensitivity distribution approaches to deriving environmental quality guidelines. AB - The species sensitivity distribution (SSD) distribution approach to estimating water quality guidelines (WQGs) is the preferred method in all jurisdictions reviewed (Australia, Canada, New Zealand, Organisation for Economic Co-operation and Development [OECD] members, South Africa, United States) and is one of the recommended methods for European Commission members for 33 priority and priority hazardous substances. In the event that jurisdiction-specific criteria for data quality, quantity, and taxonomic representation are not met, all of these jurisdictions endorse the use of additional safety factors (SFs) applied to either the SSD-based WQG or, the lowest suitable toxicity test endpoint. In Canada, the British Columbia Ministry of Environment endorses this latter approach as the preferred approach in the belief that so-derived WQGs are more protective than SSD-based WQGs. The level of protection afforded by the latter SF approach was evaluated by statistically sampling minima from random samples of the following distributions: normal, Gumbel, logistic, and Weibull, using a range of coefficients of variation (cVs) and applying the SFs of 2 or 10 used in British Columbia. The simulations indicate that the potentially affected fraction of species (PAF) can be as high as 20%, or, approach 0%. The PAF varies with sample size and CV. Because CVs can vary systematically with mode of toxic action, the PAF using SF-based WQGs can also vary systematically with analyte class. The varying levels of protection afforded by SF-based WQGs are generally inconsistent with the common water quality management goal that allows for a small degree of change under long-term exposure. The findings suggest that further efforts be made to develop high-quality WQGs that support informed decision making and are consistent with the environmental management goal instead of using SFs in the hope of achieving an acceptable but unknown, degree of environmental protection. PMID- 26272693 TI - Anxiety and Depressed Mood Decline Following Smoking Abstinence in Adult Smokers with Attention Deficit Hyperactivity Disorder. AB - INTRODUCTION: A preponderance of relevant research has indicated reduction in anxiety and depressive symptoms following smoking abstinence. This secondary analysis investigated whether the phenomenon extends to smokers with attention deficit hyperactivity disorder (ADHD). METHODS: The study setting was an 11-Week double-blind placebo-controlled randomized trial of osmotic release oral system methylphenidate (OROS-MPH) as a cessation aid when added to nicotine patch and counseling. Participants were 255 adult smokers with ADHD. The study outcomes are: anxiety (Beck Anxiety Inventory (BAI)) and depressed mood (Beck Depression Inventory II (BDI)) measured one Week and six Weeks after a target quit day (TQD). The main predictor is point-prevalence abstinence measured at Weeks 1 and 6 after TQD. Covariates are treatment (OROS-MPH vs placebo), past major depression, past anxiety disorder, number of cigarettes smoked daily, demographics (age, gender, education, marital status) and baseline scores on the BAI, BDI, and the DSM-IV ADHD Rating Scale. RESULTS: Abstinence was significantly associated with lower anxiety ratings throughout the post-quit period (p<0.001). Depressed mood was lower for abstainers than non-abstainers at Week 1 (p<0.05), but no longer at Week 6 (p=0.83). Treatment with OROS-MPH relative to placebo showed significant reductions at Week 6 after TQD for both anxiety (p<0.05) and depressed mood (p<0.001), but not at Week 1. Differential abstinence effects of gender were observed. Anxiety and depression ratings at baseline predicted increased ratings of corresponding measures during the post-quit period. CONCLUSION: Stopping smoking yielded reductions in anxiety and depressed mood in smokers with ADHD treated with nicotine patch and counseling. Treatment with OROS MPH yielded mood reductions in delayed manner. PMID- 26272694 TI - Antioxidant fractions of Khaya grandifoliola C.DC. and Entada africana Guill. et Perr. induce nuclear translocation of Nrf2 in HC-04 cells. AB - The in vitro antioxidant properties, cytoprotective activity, and ability to induce nuclear translocation of nuclear factor E2-related factor-2 (Nrf-2) of five solvent fractions of the methylene chloride/methanol (1:1 v/v) extract of Khaya grandifoliola (Meliaceae) and Entada africana (Fabaceae) were evaluated. Five antioxidant endpoints were used in the antioxidant activity investigation. The total phenolic content of the fractions was assessed as to the Folin Ciocalteu method and the profile of interesting fractions analyzed by high performance liquid chromatography (HPLC). The cytoprotective activity of fractions was determined by H2O2-induced oxidative stress in HC-04 cells by measuring lactate dehydrogenase (LDH) leakage into culture medium. HC-04 cells were used to investigate the ability to induce nuclear translocation of Nrf2. For both plants, the methylene chloride/methanol (90/10; v/v) fraction (F10), methylene chloride/methanol (75/25; v/v) (F25), and the methanolic fraction (F100) were found to have the highest total polyphenol content and exhibited high antioxidant activity strongly correlated with total polyphenol content. The cytoprotective activity of fraction F25 from both plants was comparable to that of quercetin (3.40 +/- 0.05 MUg/mL), inhibiting LDH leakage with a low half inhibition concentration (IC50) of 4.05 +/- 0.03 and 3.8 +/- 0.02 MUg/mL for K. grandifoliola and E. africana, respectively. Lastly, fraction F25 of K. grandifoliola significantly (P < 0.05) induced nuclear Nrf2 translocation by sixfold, whereas that from E. africana and quercetin was only twofold. The results indicate for the first time that fraction F25 of the studied plants is more antioxidant and cytoprotective and induces nuclear translocation of Nrf2 in a human hepatocyte cell line. PMID- 26272695 TI - Chronic unpredictable stress (CUS) enhances the carcinogenic potential of 7,12 dimethylbenz(a)anthracene (DMBA) and accelerates the onset of tumor development in Swiss albino mice. AB - Social stressors evolving from individual and population interactions produce stress reactions in many organisms (including humans), influencing homeostasis, altering the activity of the immunological system, and thus leading to various pathological states including cancer and their progression. The present study sought to validate the effectiveness of chronic unpredictable stress (CUS) in cancer promotion and to assess oxidative stress outcomes in terms of various in vivo biochemical parameters, oxidative stress markers, DNA damage, and the development of skin tumors in Swiss albino mice. Animals were randomized into different groups based on their exposure to CUS alone, 7,12 dimethylbenz(a)anthracene (DMBA) alone (topical), and DMBA-12-O tetradecanoylphorbol-13-acetate (TPA) (topical) and exposure to CUS prior to DMBA or DMBA-TPA treatments and sacrificed after 16 weeks of treatment. Prior exposure to CUS significantly increased the pro-oxidant effect of carcinogen, depicted by compromised levels of antioxidants in the circulation and skin, accompanied by enhanced lipid peroxidation, plasma corticosterone, and marker enzymes as compared to DMBA-alone or DMBA-TPA treatments. DNA damage results corroborated the above biochemical outcomes. Also, the development of skin tumors (in terms of their incidence, tumor yield, and tumor burden) in mice in the presence and absence of stress further strongly supported our above biochemical measurements. CUS may work as a promoter of carcinogenesis by enhancing the pro-oxidant potential of carcinogens. Further studies may be aimed at the development of interventions for disease prevention by identifying the relations between psychological factors and DNA damage. PMID- 26272697 TI - The Solid Solution Sr(1-x)Ba(x)Ga2: Substitutional Disorder and Chemical Bonding Visited by NMR Spectroscopy and Quantum Mechanical Calculations. AB - Complete miscibility of the intermetallic phases (IPs) SrGa2 and BaGa2 forming the solid solution Sr(1-x)Ba(x)Ga2 is shown by means of X-ray diffraction, thermoanalytical and metallographic studies. Regarding the distances of Sr/Ba sites versus substitution degree, a model of isolated substitution centres (ISC) for up to 10% cation substitution is explored to study the influence on the Ga bonding situation. A combined application of NMR spectroscopy and quantum mechanical (QM) calculations proves the electric field gradient (EFG) to be a sensitive measure of different bonding situations. The experimental resolution is boosted by orientation-dependent NMR on magnetically aligned powder samples, revealing in first approximation two different Ga species in the ISC regimes. EFG calculations using superlattice structures within periodic boundary conditions are in fair agreement with the NMR spectroscopy data and are discussed in detail regarding their application on disordered IPs. PMID- 26272696 TI - CD90+ liver cancer cells modulate endothelial cell phenotype through the release of exosomes containing H19 lncRNA. AB - BACKGROUND: CD90+ liver cancer cells have been described as cancer stem-cell-like (CSC), displaying aggressive and metastatic phenotype. Using two different in vitro models, already described as CD90+ liver cancer stem cells, our aim was to study their interaction with endothelial cells mediated by the release of exosomes. METHODS: Exosomes were isolated and characterized from both liver CD90+ cells and hepatoma cell lines. Endothelial cells were treated with exosomes, as well as transfected with a plasmid containing the full length sequence of the long non-coding RNA (lncRNA) H19. Molecular and functional analyses were done to characterize the endothelial phenotype after treatments. RESULTS: Exosomes released by CD90+ cancer cells, but not by parental hepatoma cells, modulated endothelial cells, promoting angiogenic phenotype and cell-to-cell adhesion. LncRNA profiling revealed that CD90+ cells were enriched in lncRNA H19, and released this through exosomes. Experiments of gain and loss of function of H19 showed that this LncRNA plays an important role in the exosome-mediated phenotype of endothelial cells. CONCLUSIONS: Our data indicate a new exosome-mediated mechanism by which CSC-like CD90+ cells could influence their tumor microenvironment by promoting angiogenesis. Moreover, we suggest the lncRNA H19 as a putative therapeutic target in hepatocellular carcinoma. PMID- 26272698 TI - Impact of Body Size on Inferior Vena Cava Parameters for Estimating Right Atrial Pressure: A Need for Standardization? AB - BACKGROUND: Inferior vena cava (IVC) diameter and its respiratory change, as determined using echocardiography, are commonly used to assess right atrial pressure (RAP). Despite the widespread use of the IVC approach for RAP assessment, the relations among body surface area (BSA), IVC diameter, and respirophasic change remain unclear. The aim of this study was to investigate the impact of BSA on IVC parameters for predicting elevated RAP. METHODS: Ninety consecutive patients undergoing right-heart catheterization or central venous catheter insertion were prospectively included. To investigate the impact of BSA on IVC parameters, patients were divided into higher and lower BSA groups by comparing individual BSA measurements with the median value. Optimal cutoff points of IVC parameters for detecting RAP of >= 10 mm Hg were defined using receiver operating characteristic curves. RESULTS: The median RAP and BSA were 8 mm Hg (range, 1-25 mm Hg) and 1.61 m(2) (range, 1.23-2.22 m(2)), respectively. In all patients, the optimal cutoff point for maximal IVC diameter (IVCDmax) and IVC collapsibility for the detection of RAP >= 10 mm Hg were 20 mm and 49.0%, respectively. The optimal cutoff point of IVCDmax for predicting RAP of >= 10 mm Hg was significantly larger in patients with higher BSAs than in those with lower BSAs (21 vs 17 mm, P = .0342). No differences in collapsibility indices were detected between the two groups. IVCDmax was larger in men (19 +/- 5 vs 17 +/- 5 mm in women, P = .0347) and weakly correlated with BSA (r = 0.35, P = .0007), whereas no relation was found between IVCDmax and age. However, the partial correlation coefficient of the entire cohort demonstrated that only BSA was still associated with IVCDmax after adjusting for age and gender (partial correlation coefficient = 0.32, P = .0020). CONCLUSIONS: Body size, measured as BSA, is important to consider when IVC diameter is used to assess RAP. The optimal cutoff point of IVCDmax was 21 mm for patients with larger BSAs and 17 mm for those with smaller BSAs. However, the cutoff point of IVC collapsibility was not influenced by the difference of BSA. PMID- 26272699 TI - Echocardiography before and after resect-plicate-release surgical myectomy for obstructive hypertrophic cardiomyopathy. AB - BACKGROUND: Anatomic features of obstructive hypertrophic cardiomyopathy are septal hypertrophy, elongated mitral leaflets, and anterior displacement of the papillary muscles. In addition to extended myectomy, the resect-plicate-release operation adds horizontal plication of the anterior mitral leaflet (AML) and release of the anterolateral papillary muscle (APM) in selected patients. The aim of this study was to test the hypotheses that (1) preoperative findings would be associated with procedures applied, (2) anatomic corrections would be observable postoperatively, and (3) there would be consistently good physiologic outcomes. METHODS: A retrospective study was conducted of patients with obstructive hypertrophic cardiomyopathy who had adequate echocardiograms before and 9.5 +/- 12 months after the resect-plicate-release operation was performed from 2006 to 2012. RESULTS: Seventy-seven patients underwent myectomy, 50 AML plication, and 50 APM release. Patients who underwent plication had longer AMLs (32 +/- 4 vs 28 +/- 4 mm; P < .004). Anterior extension of the APM was more common with papillary muscle release (86% vs 62%, P < .04). Twenty-seven (35%) had septal thickness <= 18 mm; mitral valve-sparing operations were possible because of plication in 19 patients (70%), papillary release in 21 (78%), and one or both in 96%. Patients who underwent plication had decreased AML length by 16%, residual leaflet length by 33%, and protrusion by 24%. After APM release, there was decreased distance from mitral coaptation to the posterior wall. Surgery abolished severe systolic anterior motion and resting gradients and reduced mitral regurgitation. CONCLUSIONS: Echocardiographic AML length and directly observed slack provides a basis to recommend performance of plication and define its extent; plication decreases AML protrusion and stiffens the leaflet. Anterior APM recommends release, which drops the coaptation point posteriorly. Systematic relief of all aspects of obstructive pathophysiology results in consistent outcomes. PMID- 26272700 TI - Intra-abdominal ALK-positive anaplastic large cell lymphoma in a patient with neurofibromatosis type 1. PMID- 26272701 TI - High-Yield Spreading of Water-Miscible Solvents on Water for Langmuir-Blodgett Assembly. AB - Langmuir-Blodgett (LB) assembly is a classical molecular thin-film processing technique, in which the material is spread onto water surface from a volatile, water-immiscible solvent to create floating monolayers that can be later transferred to solid substrates. LB has also been applied to prepare colloidal thin films with an unparalleled level of microstructural control and thickness, which has enabled the discovery of many exciting collective properties of nanoparticles and the construction of bulk nanostructured materials. To maximize the benefits of LB assembly, the nanoparticles should be well dispersed in both the spreading solvent and on water. This is quite challenging since colloids usually need contrasting surface properties in order to be stable in the water hating organic solvents and on water surface. In addition, many organic and polymeric nanostructures dissolve in those organic solvents and cannot be processed directly. Using water-liking spreading solvents can avoid this dilemma. However, spreading of water-miscible solvents on water surface is fundamentally challenging due to extensive mixing, which results in significant material loss. Here we report a conceptually simple strategy and a general technique that allows nearly exclusive spreading of such solvents on water surface using electrospray. Since the volume of these aerosolized droplets is reduced by many orders of magnitude, they are readily depleted during the initial spreading step before any significant mixing could occur. The new strategy drastically reduces the burden of material processing prior to assembly and broadens the scope of LB assembly to previously hard-to-process materials. It also avoids the use of toxic volatile organic spreading solvents, improves the reproducibility, and can be readily automated, making LB assembly a more robust tool for colloidal assembly and thin film fabrication. PMID- 26272702 TI - Examination of a plasmid-based reverse genetics system for human astrovirus. AB - A plasmid-based reverse genetics system for human astrovirus type 1 (HAstV1) is examined. Upon transfection into 293T cells, the plasmid vector, which harbors a HAstV1 expression cassette, expressed astroviral RNA that appeared to be capable of viral RNA replication, as indicated by the production of subgenomic RNA and capsid protein expression irrespective of the heterologous 5' ends of the transcribed RNA. Particles infectious to Caco-2 cells were made in this system; however, their infectivity was much lower than would be expected from the amount of particles apparently produced. Using Huh-7 cells as the transfection host with the aim of improving viral capsid processing for virion maturation partially restored the efficiency of infectious particle formation. Our results support the possibility that the DNA transfection process induces a cellular response that targets late, but not early, stages of HAstV1 infection. PMID- 26272703 TI - Anatomical configuration of the inferior alveolar neurovascular bundle: a histomorphometric analysis. AB - PURPOSE: The inferior alveolar neurovascular bundle (NVB) is important in implant placement and many other surgeries in dentistry because it is a major supplier of sensation and blood to the mandible via the mandibular canal. The purposes of the present study were to determine the areas and diameters of the NVB, the inferior alveolar nerve (IAN), and the inferior alveolar artery (IAA), and to verify the buccolingual location of the mandibular canal. METHODS: The anatomical configuration of the NVB was examined by histomorphometrically analyzing 20 embalmed dentulous hemimandibles. The areas and maximum horizontal and vertical diameters of the NVB, IAN, and IAA were measured according to tooth region. The distances from the internal border of the mandibular canal to the outer surface of the buccal and lingual cortical plates were also measured. RESULTS: The areas of the vertically oval-shaped NVB and IAN appeared to be constant between the molar and premolar regions, which contain the mental branch, and decreased sharply in the lateral incisor after branching off of the mental branch via the mental canal. The mandibular canal was located close to the lingual cortical plate in the posterior tooth region before passing through the mental canal, immediately after which it was situated quite close to the buccal cortical plate, and then closer to the middle toward the anterior tooth region. CONCLUSIONS: The findings of this study provide useful anatomical information that should help to minimize the risk of injury to the NVB during surgical procedures in the mandibular region. PMID- 26272705 TI - Breast Biopsies Under Magnetic Resonance Imaging Guidance: Challenges of an Essential but Imperfect Technique. AB - Magnetic resonance imaging (MRI)-guided breast biopsy is an essential tool of a breast imager; yet, a decade after its introduction, this technique remains challenging and imperfect. This article presents the technique of MRI-guided biopsy, with an emphasis on challenges particular to the technique: technical considerations related to adequate lesion sampling and difficulties in confirming radiologic-pathologic correlation for enhancing lesions. Through clinical vignettes, challenges unique to MRI-guided biopsy are discussed and practical tips are offered. Prebiopsy planning including second-look targeted studies, patient preparation, and equipment is covered. Challenging situations pertaining to breast size, lesion location, or type of enhancement are illustrated, as well as the topic of performing multiple MRI-guided breast biopsies in a single session and biopsies of women with implants. Postbiopsy management is discussed. Success of MRI-guided biopsies requires careful prebiopsy planning, as well as appropriate choice of biopsy device, optimized for the specifics of breast shape and lesion size and location. Special features of biopsy systems (smaller apertures and blunt tips) facilitate the sampling of lesions in challenging locations. Vanishing lesions should undergo short-term follow-up, because malignancy cannot be excluded, as should lesions diagnosed as benign after pathologic analysis when the result is felt to be concordant with imaging features. To this end, radiologic-pathologic correlation is essential. Underestimation rates after MRI-guided breast biopsy are superior to those for vacuum-assisted stereotactic biopsy and ultrasound-guided biopsy. Close follow-up and rebiopsy should be considered when there is imaging-discordant histology. For benign and concordant histology, a first follow-up can be offered at 6 months. PMID- 26272704 TI - Incidence of post-obturation pain after single-visit versus multiple-visit non surgical endodontic treatments. AB - BACKGROUND: Post-obturation pain is frustrating to both patients and dentists. Its incidence may change with the use of contemporary endodontic techniques. This randomised clinical trial aims to compare the incidence of post-obturation pain at one and seven days after single-visit and multiple-visit non-surgical endodontic treatments. METHODS: Patients who required primary endodontic treatment in the two clinical trial centres in Hong Kong (HK) and in Beijing (PK) were recruited. Three HK dentists and three PK dentists performed endodontic treatments on 567 teeth using the same procedures and materials, either in a single visit or over multiple visits, using either core carrier or cold lateral condensation for obturation. RESULTS: The attrition rate was 5.1%, and a total of 538 teeth were evaluated. Among these teeth, 232 (43%) were operated in HK, 275 (51%) were treated in a single visit, and 234 (43%) were treated using core carrier obturation. Logistic regression analysis showed that teeth with apical periodontitis (OR = 0.35, 95% CI = 0.21-0.57, p < 0.01) and less pre-operative pain (OR = 1.10, 95% CI = 1.03-1.18, p < 0.01) had lower incidences of post obturation pain after one day. The incidences of post-obturation pain after one day for single-visit and multiple-visit treatments were 24.7% (68 of 275) and 33.5% (88 of 263), respectively (p = 0.50). The incidences of post-obturation pain after seven days for single-visit and multiple-visit treatments were 4.0% (11 of 275) and 5.3% (14 of 263), respectively (p = 0.47). CONCLUSIONS: There was no significant difference in the incidences of post-obturation pain after one day and seven days with single-visit or multiple-visit endodontic treatments. TRIAL REGISTRATION: ChiCTR-IOR-15005989. PMID- 26272706 TI - Inhibiting oral intoxication of botulinum neurotoxin A complex by carbohydrate receptor mimics. AB - Botulinum neurotoxins (BoNTs) cause the disease botulism manifested by flaccid paralysis that could be fatal to humans and animals. Oral ingestion of the toxin with contaminated food is one of the most common routes for botulism. BoNT assembles with several auxiliary proteins to survive in the gastrointestinal tract and is subsequently transported through the intestinal epithelium into the general circulation. Several hemagglutinin proteins form a multi-protein complex (HA complex) that recognizes host glycans on the intestinal epithelial cell surface to facilitate BoNT absorption. Blocking carbohydrate binding to the HA complex could significantly inhibit the oral toxicity of BoNT. Here, we identify lactulose, a galactose-containing non-digestible sugar commonly used to treat constipation, as a prototype inhibitor against oral BoNT/A intoxication. As revealed by a crystal structure, lactulose binds to the HA complex at the same site where the host galactose-containing carbohydrate receptors bind. In vitro assays using intestinal Caco-2 cells demonstrated that lactulose inhibits HA from compromising the integrity of the epithelial cell monolayers and blocks the internalization of HA. Furthermore, co-administration of lactulose significantly protected mice against BoNT/A oral intoxication in vivo. Taken together, these data encourage the development of carbohydrate receptor mimics as a therapeutic intervention to prevent BoNT oral intoxication. PMID- 26272707 TI - Hemiparetic gait and changes in functional performance due to OnabotulinumtoxinA injection to lower limb muscles. AB - OBJECTIVE: To review gait alterations and evaluate the effects of OnabotulinumtoxinA on spatiotemporal walking parameters of patients with hemiparetic gait. DESIGN: Retrospective pre- and post-intervention analysis. SETTING: Gait analysis laboratory in a tertiary level rehabilitation hospital. PARTICIPANTS: 42 patients with hemiparesis. 19 males and 23 females, age 18-78 years were included. INTERVENTION: Spatiotemporal parameters collected before and within 4-10 weeks after OnabotA injection to the ankle muscles. Data was recorded at self-selected velocity on a 12 m instrumented walkway. The most common muscles injected were medial and lateral gastrocnemius, soleus and tibialis posterior. Average total OnabotulinumtoxinA dose was 320 +/- 107 units. MAIN OUTCOME: Spatiotemporal parameters of walking assessed before (T0) and within 4-10 weeks post injection (T1). Paired t-test was used to compare pre- and post-intervention data. A sequential Holm-Bonferroni procedure was used to adjust for multiple comparisons and minimize the risk of type I error. Statistical significance was set at p < 0.05. RESULTS: Statistically significant increases were seen for walking velocity (20%) (T0 = 0.40 +/- 0.26 m/s and T1 = 0.48 +/- 0.29 m/s; p = 0.006), and increased cadence (T0 = 63.48 +/- 23.93 steps/min, and T1 = 70.88 +/- 23.65 steps/min; p = 0.006) following OnabotulinumtoxinA injections. CONCLUSION: This study demonstrates that injection of OnabotulinumtoxinA 320 units to ankle muscles selected with the aid of dynamic electromyography can significantly increase gait velocity and enhance functional ambulation in adults with hemiparesis due to upper motor neuron syndrome. PMID- 26272708 TI - Characterization of Neuwiedin, a new disintegrin from Bothrops neuwiedi venom gland with distinct cysteine pattern. AB - Disintegrins are cysteine-rich toxins containing the RGD motif exposed in a loop that binds integrins such as alphaIIbbeta3, alpha5beta1 and alphavbeta3. The flexibility of the RGD loop, controlled by the profile of the cysteine pairs and the residues flanking the RGD sequence, are key structural features for the functional activity of these molecules. Recently, our group reported a transcript in the venom gland of Bothrops neuwiedi corresponding to a new P-II SVMP precursor, BnMPIIx, in which the RGD-binding loop includes many substituted residues and unique cysteine residues at the C-terminal. In this paper, we obtained the recombinant disintegrin domain of BnMPIIx, Neuwiedin, which inhibited ADP-induced platelet aggregation, endothelial cell adhesion to fibrinogen and tube formation in Matrigel with no particular selectivity to alphaIIbbeta3 or endothelial cell integrins. This value was also comparable to the inhibition observed with other recombinant disintegrins with conserved cysteine positions and residues in RGD loop. In this regard, Neuwiedin is an important component to understand the functional relevance of the diversity generated by accelerated evolution of venom toxins as well as to find out eventual new disintegrin-dependent targets that may be approached with disintegrins. PMID- 26272709 TI - GenomewidePDB 2.0: A Newly Upgraded Versatile Proteogenomic Database for the Chromosome-Centric Human Proteome Project. AB - Since the launch of the Chromosome-centric Human Proteome Project (C-HPP) in 2012, the number of "missing" proteins has fallen to 2932, down from ~5932 since the number was first counted in 2011. We compared the characteristics of missing proteins with those of already annotated proteins with respect to transcriptional expression pattern and the time periods in which newly identified proteins were annotated. We learned that missing proteins commonly exhibit lower levels of transcriptional expression and less tissue-specific expression compared with already annotated proteins. This makes it more difficult to identify missing proteins as time goes on. One of the C-HPP goals is to identify alternative spliced product of proteins (ASPs), which are usually difficult to find by shot gun proteomic methods due to their sequence similarities with the representative proteins. To resolve this problem, it may be necessary to use a targeted proteomics approach (e.g., selected and multiple reaction monitoring [S/MRM] assays) and an innovative bioinformatics platform that enables the selection of target peptides for rarely expressed missing proteins or ASPs. Given that the success of efforts to identify missing proteins may rely on more informative public databases, it was necessary to upgrade the available integrative databases. To this end, we attempted to improve the features and utility of GenomewidePDB by integrating transcriptomic information (e.g., alternatively spliced transcripts), annotated peptide information, and an advanced search interface that can find proteins of interest when applying a targeted proteomics strategy. This upgraded version of the database, GenomewidePDB 2.0, may not only expedite identification of the remaining missing proteins but also enhance the exchange of information among the proteome community. GenomewidePDB 2.0 is available publicly at http://genomewidepdb.proteomix.org/. PMID- 26272710 TI - Fine grain separation for the production of biomass fuel from mixed municipal solid waste. AB - The main goal of the project MARSS (Material Advanced Sustainable Systems) is to build a demonstration plant in order to recover a renewable biomass fuel suitable for the use in biomass power plants out of mixed municipal solid waste (MMSW). The demonstration plant was constructed in Mertesdorf (Germany), working alongside an existing mechanical-biological treatment plant, where the MMSW is biological dried under aerobe conditions in rotting boxes. The focus of the presented sorting campaign was set on the processing of fine grain particles minor than 11.5mm which have the highest mass content and biogenic energy potential of the utilized grain size fractions. The objective was to produce a biomass fuel with a high calorific value and a low content of fossil (plastic, synthetic) materials while maximizing the mass recovery. Therefore, the biogenic components of the dried MMSW are separated from inert and fossil components through various classification and sifting processes. In three experimental process setups of different processing depths, the grain size fraction 4-11.5mm was sifted by the use of air sifters and air tables. PMID- 26272711 TI - Enhanced mesophilic anaerobic digestion of food waste by thermal pretreatment: Substrate versus digestate heating. AB - Food waste (FW) represents a source of high potential renewable energy if properly treated with anaerobic digestion (AD). Pretreating the substrates could yield a higher biomethane production in a shorter time. In this study, the effects of thermal (heating the FW in a separate chamber) and thermophilic (heating the full reactor content containing both FW and inoculum) pretreatments at 50, 60, 70 and 80 degrees C prior to mesophilic AD were studied through a series of batch experiments. Pretreatments at a lower temperature (50 degrees C) and a shorter time (<12h) had a positive effect on the AD process. The highest enhancement of the biomethane production with an increase by 44-46% was achieved with a thermophilic pretreatment at 50 degrees C for 6-12h or a thermal pretreatment at 80 degrees C for 1.5h. Thermophilic pretreatments at higher temperatures (>55 degrees C) and longer operating times (>12h) yielded higher soluble chemical oxygen demand (CODs), but had a negative effect on the methanogenic activity. The thermal pretreatments at the same conditions resulted in a lower solubilization of COD. Based on net energy calculations, the enhanced biomethane production is sufficient to heat up the FW for the thermal, but not for the thermophilic pretreatment. PMID- 26272713 TI - Validation of a modified FRAX(r) tool for improving outpatient efficiency--part of the "Catch Before a Fall" initiative. AB - We have validated our touch-screen-modified FRAX(r) tool against the traditional healthcare professional-led questionnaire, demonstrating strong concordance between doctor- and patient-derived results. We will use this in outpatient clinics and general practice to increase our capture rate of at-risk patients, making valuable use of otherwise wasted patient waiting times. INTRODUCTION: Outpatient clinics offer an opportunity to collect valuable health information from a captive population. We have previously developed a modified fracture risk assessment (FRAX(r)) tool, enabling patients to self-assess their osteoporotic fracture risk in a touch-screen computer format and demonstrated its acceptability with patients. We aim to validate the accuracy of our tool against the traditional questionnaire. METHODS: Fifty patients over 50 years of age within the fracture clinic independently completed a paper equivalent of our touch-screen-modified FRAX(r) questionnaire. Responses were analysed against the traditional healthcare professional (HCP)-led questionnaire which was carried out afterwards. Correlation was assessed by sensitivity, specificity, Cohen's kappa statistic and Fisher's exact test for each potential FRAX(r) outcome of "treat", "measure BMD" and "lifestyle advice". RESULTS: Age range was 51-98 years. The FRAX(r) tool was completed by 88 % of patients; six patients lacked confidence in estimating either their height or weight. Following question adjustment according to patient response and feedback, our tool achieved >95 % sensitivity and specificity for the "treat" and "lifestyle advice" groups, and 79 % sensitivity and 100 % specificity in the "measure BMD" group. Cohen's kappa value ranged from 0.823 to 0.995 across all groups, demonstrating "very good" agreement for all. Fisher's exact test demonstrated significant concordance between doctor and patient decisions. DISCUSSION: Our modified tool provides a simple, accurate and reliable method for patients to self-report their own FRAX(r) score outside the clinical contact period, thus releasing the HCP from the time required to complete the questionnaire and potentially increasing our capture rate of at-risk patients. PMID- 26272712 TI - New vertebral fractures after vertebroplasty: 2-year results from a randomised controlled trial. AB - A randomised controlled trial of vertebroplasty (VP) versus placebo assessed the effect of VP on the risk of further vertebral fractures. While no statistically significant between-group differences for new or progressed fracture risk at 12 and 24 months were observed, we observed a consistent trend towards higher risk of any type of fracture in the group undergoing VP. Our analysis was underpowered, and further adequately powered studies are needed to be able to draw firm conclusions about further vertebral risk with vertebroplasty. PURPOSE: This study seeks to assess the effect of VP on the risk of further radiologically apparent vertebral fracture within two years of the procedure. METHODS: We conducted a randomised placebo-controlled trial of VP in people with acute osteoporotic vertebral fracture. Eligible participants were randomly assigned to VP (n = 38) or placebo (n = 40). Cement volume and leakage were recorded for the VP group. Plain thoracolumbar radiographs were taken at baseline, 12 and 24 months. Two independent radiologists assessed these for new and progressed fractures at the same, adjacent and non-adjacent levels. RESULTS: At 12 and 24 months, radiographs were available for 45 (58 %) and 47 (60 %) participants, respectively. There were no between-group differences for new or progressed fractures: 32 and 40 in the VP group after 12 and 24 months compared with 21 and 33 in the placebo group (hazard ratio (HR) 1.80, 95 % confidence interval (CI) 0.82 to 3.94). Similar results were seen when considering only adjacent (HR (95 % CI) 2.30 (0.57 to 9.29)) and non-adjacent (HR (95 % CI) 1.45 (0.55 to 3.81) levels. In all comparisons, there was a consistent trend towards higher risk of any type of fracture in the group undergoing VP. Within the VP group, fracture risk was unrelated to total (HR (95 % CI) 0.91 (0.71 to 1.17)) or relative (HR (95 % CI) 1.31 (0.15 to 11.48)) cement volume or cement leakage (HR (95 % CI) 1.20 (0.63 to 2.31)). CONCLUSION: For patients undergoing VP, our study did not demonstrate significant increases in subsequent fracture risk beyond that experienced by those with vertebral fractures who did not undergo the procedure. However, because of the non-significant numerical increases observed, studies with adequate power are needed to draw definite conclusions about fracture risk. PMID- 26272714 TI - Enhanced elimination of dabigatran: Identifying the appropriate patient for the use of continuous venovenous hemodialysis instead of intermittent hemodialysis-A simulation analysis. AB - There are clinical situations where rapid elimination of dabigatran is beneficial. Intermittent hemodialysis (IHD) removes dabigatran effectively but is not always available and requires a hemodynamically stable patient. We therefore investigated the continuous venovenous hemodialysis (CVVHD) technique for its potency in the elimination of dabigatran. Based on pharmacometric characterization of dabigatran in IHD, we simulated a broad range of dialysis settings for CVVHD and then applied the model to specific clinical situations. Dialysis of 3 hours' duration with typical clinical settings (dialysate flow rate 50 mL/min; blood flow rate 150 mL/min) reduced dabigatran plasma concentration by 14-17% in addition to the patient body clearance. Extending dialysis duration to 8 or 16 hours for patients with severe renal dysfunction resulted in additional reductions from 26% up to 40%. When comparing with IHD for different endpoints (reaching 50% of initial dabigatran concentration, or nondetectability of dabigatran by the Hemoclot test), CVVHD did not reach comparable elimination rates. CVVHD is not fast enough to prepare for urgent interventions in patients with high bleeding risks. However, in situations where less hemodynamically stressful modalities seem indicated, CVVHD might be useful in moderately to severely renally impaired patients to accelerate dabigatran elimination. PMID- 26272715 TI - Attitudes towards couples HIV testing and counseling among Latino men who have sex with men in the Seattle area. AB - Men who have sex with men (MSM) remain the most severely affected risk group in the US HIV/AIDS epidemic. One-third to two-thirds of HIV transmissions among MSM are estimated to come from primary sex partners. Couples HIV testing and counseling (CHTC), in which two individuals receive pre-test counseling, HIV testing and post-test prevention planning together, has been adapted for male couples in the USA, and is now available in more than 30 cities. Previous studies have demonstrated high levels of willingness to use CHTC among MSM, but to date no studies have explored this among Latino MSM (LMSM). To examine the willingness to use CHTC among and further cultural adaptation needed for LMSM, focus group discussions were held with men who self-identified as Latino, were in a relationship with another man, and resided in Seattle. Willingness to use CHTC was high. Participants reported that CHTC could strengthen and validate their relationships, help mitigate stigma, and provide a forum for support, protection, and information sharing. Barriers to CHTC use included fears of rejection, loneliness, and relationship dissolution, and concerns around deportation and financial burden. The high levels of reported willingness to use CHTC among this sample of LMSM point to the potential for CHTC to be further adapted to provide dyadic HIV testing services for LMSM. PMID- 26272716 TI - Chemoreceptor Evolution in Hymenoptera and Its Implications for the Evolution of Eusociality. AB - Eusocial insects, mostly Hymenoptera, have evolved unique colonial lifestyles that rely on the perception of social context mainly through pheromones, and chemoreceptors are hypothesized to have played important adaptive roles in the evolution of sociality. However, because chemoreceptor repertoires have been characterized in few social insects and their solitary relatives, a comprehensive examination of this hypothesis has not been possible. Here, we annotate ~3,000 odorant and gustatory receptors in recently sequenced Hymenoptera genomes and systematically compare >4,000 chemoreceptors from 13 hymenopterans, representing one solitary lineage (wasps) and three independently evolved eusocial lineages (ants and two bees). We observe a strong general tendency for chemoreceptors to expand in Hymenoptera, whereas the specifics of gene gains/losses are highly diverse between lineages. We also find more frequent positive selection on chemoreceptors in a facultative eusocial bee and in the common ancestor of ants compared with solitary wasps. Our results suggest that the frequent expansions of chemoreceptors have facilitated the transition to eusociality. Divergent expression patterns of odorant receptors between honeybee and ants further indicate differential roles of chemoreceptors in parallel trajectories of social evolution. PMID- 26272717 TI - Assessing Recent Selection and Functionality at Long Noncoding RNA Loci in the Mouse Genome. AB - Long noncoding RNAs (lncRNAs) are one of the most intensively studied groups of noncoding elements. Debate continues over what proportion of lncRNAs are functional or merely represent transcriptional noise. Although characterization of individual lncRNAs has identified approximately 200 functional loci across the Eukarya, general surveys have found only modest or no evidence of long-term evolutionary conservation. Although this lack of conservation suggests that most lncRNAs are nonfunctional, the possibility remains that some represent recent evolutionary innovations. We examine recent selection pressures acting on lncRNAs in mouse populations. We compare patterns of within-species nucleotide variation at approximately 10,000 lncRNA loci in a cohort of the wild house mouse, Mus musculus castaneus, with between-species nucleotide divergence from the rat (Rattus norvegicus). Loci under selective constraint are expected to show reduced nucleotide diversity and divergence. We find limited evidence of sequence conservation compared with putatively neutrally evolving ancestral repeats (ARs). Comparisons of sequence diversity and divergence between ARs, protein-coding (PC) exons and lncRNAs, and the associated flanking regions, show weak, but significantly lower levels of sequence diversity and divergence at lncRNAs compared with ARs. lncRNAs conserved deep in the vertebrate phylogeny show lower within-species sequence diversity than lncRNAs in general. A set of 74 functionally characterized lncRNAs show levels of diversity and divergence comparable to PC exons, suggesting that these lncRNAs are under substantial selective constraints. Our results suggest that, in mouse populations, most lncRNA loci evolve at rates similar to ARs, whereas older lncRNAs tend to show signals of selection similar to PC genes. PMID- 26272718 TI - Chemical Analysis in the Corpus Callosum Following Traumatic Axonal Injury using Fourier Transform Infrared Microspectroscopy: A Pilot Study. AB - Evaluating traumatic axonal injury remains challenging in clinical and forensic sciences as its identification is difficult using routine diagnostic methods. This study used Fourier transform infrared microspectroscopy to detect TAI within the corpus callosum in an animal model. Protein conformational analysis revealed significantly increased beta-sheet and beta-turn contents paralleled by a decrease in alpha-helix content at 24 h postinjury, while the antiparallel beta sheet content was decreased at 12 h postinjury. Compared with the control group, the lipid/protein ratio was significantly reduced in all of the injured groups. At 24 h postinjury, there were increases in the olefinic=CH and CH3 group of lipids accompanied by the decreased CH2 group, but the results at 12 and 72 h were contrary to that at 24 h. Our study showed that FTIRM could differentiate injured from normal white matter at different time points following TBI via examination of these infrared spectral parameters. PMID- 26272720 TI - Prophylactic intravenous ephedrine to minimize fetal bradycardia after combined spinal-epidural labour analgesia: a randomized controlled study. AB - BACKGROUND: The combined spinal-epidural (CSE) technique for relief of labour pain offers both rapid onset and superior first-stage analgesia. Nevertheless, the known increased risk for early profound fetal bradycardia (EPFB) following CSE continues to be a concern that often limits its use. The purpose of this study was to determine if giving prophylactic intravenous ephedrine at the time of CSE administration would reduce EPFB. METHODS: We conducted this clinical trial at a large community hospital and enrolled healthy patients requesting epidural analgesia for labour. Patients were randomly assigned to receive either normal saline placebo or ephedrine 10 mg iv at the time of CSE. The primary outcome of EPFB (defined as bradycardia < 90 beats.min(-1) for > two minutes and occurring within the first 30 min after CSE) was compared between groups. The secondary outcomes included the incidence of urgent cesarean delivery, the requirement for additional doses of ephedrine, maternal blood pressure, uterine hypertonus and tachysystole, and abnormal fetal heart rate (FHR) patterns before and after CSE. RESULTS: There were 299 women randomized to the ephedrine (EPH) group and 297 randomized to the normal saline placebo (NS) group. There was no difference between groups in the incidence of EPFB (2.7% EPH group vs 4.7% NS group; relative risk, 0.57; 95% confidence interval, 0.24 to 1.33; P = 0.184). There was also no difference between groups in the incidence of urgent cesarean delivery, uterine hypertonus, uterine tachysystole, and abnormal FHR patterns. CONCLUSIONS: We conclude that prophylactic intravenous ephedrine administration at the time of CSE during labour was ineffective at reducing the risk for EPFB associated with CSE. Nevertheless, a lower than expected rate of EPFB resulted in the trial being underpowered. This trial was registered at ClinicalTrials.gov, identifier: NCT02062801. PMID- 26272721 TI - Interfacial polymerization of conductive polymers: Generation of polymeric nanostructures in a 2-D space. AB - In the recent advances in the field of conductive polymers, the fibrillar or needle shaped nanostructures of polyaniline and polypyrrole have attracted significant attention due to the potential advantages of organic conductors that exhibit low-dimensionality, uniform size distribution, high crystallinity and improved physical properties compared to their bulk or spherically shaped counterparts. Carrying the polymerization reaction in a restricted two dimensional space, instead of the three dimensional space of the one phase solution is an efficient method for the synthesis of polymeric nanostructures with narrow size distribution and small diameter. Ultra-thin nanowires and nanofibers, single crystal nanoneedles, nanocomposites with noble metals or carbon nanotubes and layered materials can be efficiently synthesized with high yield and display superior performance in sensors and energy storage applications. In this critical review we will focus not only on the interfacial polymerization methods that leads to polymeric nanostructures and composites and their properties, but also on the mechanism and the physico-chemical processes that govern the diffusion and reactivity of molecules and nanomaterials at an interface. Recent advances for the synthesis of conductive polymer composites with an interfacial method for energy storage applications and future perspectives are presented. PMID- 26272719 TI - Intrathecal hyperbaric 2% prilocaine versus 0.4% plain ropivacaine for same-day arthroscopic knee surgery: a prospective randomized double-blind controlled study. AB - BACKGROUND: Short-duration spinal anesthesia is a good option for ambulatory knee surgery. Hyperbaric 2% prilocaine has short onset and rapid recovery times and, therefore, may be well suited in this setting. The aim of this study was to compare the times to reach motor block, motor block resolution, and discharge from the postanesthesia care unit (PACU) between hyperbaric 2% prilocaine and 0.4% plain ropivacaine. METHODS: In this prospective randomized double-blind study, 140 patients (ages 18-80 yr and American Society of Anesthesiologists physical status I-II) scheduled for elective unilateral arthroscopic knee surgery lasting < 45 min were allocated to either 3 mL of 2% prilocaine (60 mg) or 3 mL of 0.4% plain ropivacaine (12 mg). Time to reach complete recovery of motor block, time to reach criteria for discharge, as well as side effects up to 48 hr after discharge were recorded. RESULTS: The median (interquartile range [IQR]) time to recovery from the motor block was faster in the 2% prilocaine group compared with the 0.4% ropivacaine group (180 [169-240] min vs 240 [180-300] min, respectively; median difference, 60 min, 95% confidence interval (CI), 23 to 97 min; P = 0.036). The median [IQR] time to reach discharge criteria was similar between the two groups (330 [295-365] min vs, 335 [290-395] min; median difference 5 min, 95% CI, -25 to 35 min; P = 0.330). The incidence of side effects was low and similar in both groups. No case of transient neurologic symptoms occurred in either group. CONCLUSION: The recovery of motor block was faster after intrathecal administration of hyperbaric 2% prilocaine compared with 0.4% plain ropivacaine; however, discharge time was similar between the two groups. Both drugs showed a similar risk profile. PMID- 26272722 TI - Visualizing nanoscale 3D compositional fluctuation of lithium in advanced lithium ion battery cathodes. AB - The distribution of cations in Li-ion battery cathodes as a function of cycling is a pivotal characteristic of battery performance. The transition metal cation distribution has been shown to affect cathode performance; however, Li is notoriously challenging to characterize with typical imaging techniques. Here laser-assisted atom probe tomography (APT) is used to map the three-dimensional distribution of Li at a sub-nanometre spatial resolution and correlate it with the distribution of the transition metal cations (M) and the oxygen. As fabricated layered Li1.2Ni0.2Mn0.6O2 is shown to have Li-rich Li2MO3 phase regions and Li-depleted Li(Ni0.5Mn0.5)O2 regions. Cycled material has an overall loss of Li in addition to Ni-, Mn- and Li-rich regions. Spinel LiNi0.5Mn1.5O4 is shown to have a uniform distribution of all cations. APT results were compared to energy dispersive spectroscopy mapping with a scanning transmission electron microscope to confirm the transition metal cation distribution. PMID- 26272724 TI - Prevalence and Spatial Distribution of Salmonella Infections in the Pennsylvania Raccoon (Procyon lotor). AB - A study was conducted to determine the prevalence and spatial distribution of Salmonella infection in Pennsylvania raccoons (Procyon lotor), common wildlife mammals known to occupy overlapping habitats with humans and domestic food animals. The Pennsylvania Game Commission provided a total of 371 raccoon intestinal samples from trapped and road-killed raccoons collected between May and November 2011. Salmonella was isolated from the faeces of 56 (15.1%) of 371 raccoons in 35 (54%) of 65 counties across Pennsylvania. The five most frequently isolated serotypes were Newport (28.6%), Enteritidis (19.6%), Typhimurium (10.7%), Braenderup (8.9%) and Bareilly (7.1%). Pulsed-field gel electrophoresis (PFGE) analysis of the Salmonella isolates and subsequent comparison to the Pennsylvania Department of Health human Salmonella PFGE database revealed 16 different pulsetypes in Salmonella isolates recovered from raccoons that were indistinguishable from pulsetypes of Salmonella collected from clinically ill humans during the study period. The pulsetypes of seven raccoon Salmonella isolates matched those of 56 human Salmonella isolates by month and geographical region of sample collection. Results from Clustered Regularly Interspaced Short Palindromic Repeats and Multi-Virulence Locus Sequence Typing (CRISPR-MVLST) analysis corroborated the PFGE and serotyping data. The findings of this study show that several PFGE pulsetypes of Salmonella were shared between humans and raccoons in Pennsylvania, indicating that raccoons and humans might share the same source of Salmonella. PMID- 26272723 TI - Genome-wide survey and expression analysis of the calcium-dependent protein kinase gene family in cassava. AB - Calcium-dependent protein kinases (CPKs) play important roles in regulating plant tolerance to abiotic stress and signal transduction; however, no data are currently available regarding the CPK family in cassava. Herein, we identified 27 CPK genes from cassava based on our previous genome sequencing data. Phylogenetic analysis showed that cassava CPKs could be clustered into three groups, which was further supported by gene structure and conserved protein motif analyses. Global expression analysis suggested that MeCPK genes showed distinct expression patterns in different tissues between wild subspecies and cultivated varieties, indicating their involvement in the functional diversity of different varieties. Transcriptomics, interaction networks, and co-expression assays revealed a broad transcriptional response of cassava CPKs and CPK-mediated networks to drought stress and their differential expression profiles in different varieties, implying their contribution to drought stress tolerance in cassava. Expression analysis of eight MeCPK genes suggested a comprehensive response to osmotic stress, salt, cold, abscisic acid, and H2O2, which indicated that cassava CPKs might be convergence points for different signaling pathways. This study provides a basis for crop improvements and understanding of abiotic stress responses and signal transduction mediated by CPKs in cassava. PMID- 26272725 TI - Short-term anesthesia inhibits formalin-induced extracellular signal-regulated kinase (ERK) activation in the rostral anterior cingulate cortex but not in the spinal cord. AB - BACKGROUND: The rostral anterior cingulate cortex (rACC) has been implicated in the negative affective response to injury, and importantly, it has been shown that activation of extracellular signal-regulated kinase (ERK) signaling in the rACC contributes to the full expression of the affective component of pain in rodents. In this study, we investigated whether administration of anesthesia at the time of injury could reduce phosphorylated-ERK (PERK) expression in the rACC, which might eliminate the negative affective component of noxious stimulation. Intraplantar hindpaw formalin stimulation, an aversive event in the awake animal, was given with or without general isoflurane anesthesia, and PERK expression was subsequently quantified in the rACC using immunohistochemistry. Furthermore, as numerous studies have demonstrated the importance of spinal ERK signaling in the regulation of nociceptive behaviour, we also examined PERK in the superficial dorsal horn of the spinal cord. FINDINGS: Formalin injection with and without short-term (<10 min) general isoflurane anesthesia induced the same level of PERK expression in spinal cord laminae I-II. However, PERK expression was significantly inhibited across all laminae of the rACC in animals anesthetized during formalin injection. The effect of anesthesia was such that levels of PERK were the same in formalin and sham treated anesthesized animals. CONCLUSIONS: This study is the first to demonstrate that isoflurane anesthesia can inhibit formalin-induced PERK in the rACC and therefore might eliminate the unpleasantness of restraint associated with awake hindpaw injection. PMID- 26272726 TI - A case of indeterminate dendritic cell tumor presenting with leonine facies. AB - BACKGROUND: Indeterminate dendritic cell tumor is an extremely rare neoplastic proliferation of dendritic cells that share immunophenotypic features of Langerhans cells and macrophages but lack Birbeck granules and Langerin expression. METHODS: We report a 55-year-old female presenting with a leonine facies and generalized multiple confluent papules, nodules and plaques on neck, upper trunk, arms and thighs. Laboratory evaluations were performed including skin biopsies, peripheral blood flow cytometry and positron emission tomography computed tomography. RESULTS: The lesional skin biopsy showed a dense dermal and perifollicular infiltrate composed of histiocytoid cells with nuclear grooves lacking dendritic processes in a background of lymphocytes. Eosinophils were absent. The histiocytoid cells were CD68+CD1a+Langerin- and only focally S100+. Special stains including GMS, Gram and Fite were all negative for infectious organisms. Although an initial diagnosis suggesting Langerhans cell histiocytosis was proposed due to CD1a positivity, a diagnosis of indeterminate dendritic cell tumor was finally rendered based on the histopathological findings and the lack of expression of Langerin. CONCLUSION: This case illustrates the variegated clinical presentation of indeterminate cell tumor and the necessity of appropriate immunohistochemical workup for its diagnosis. PMID- 26272727 TI - Semi-automated biobank sample processing with a 384 high density sample tube robot used in cancer and cardiovascular studies. AB - BACKGROUND: In the postgenomic era, it has become evident that analysis of genetic and protein expression changes alone is not sufficient to understand most disease processes in e.g. cardiovascular and cancer disease. Biobanking has been identified as an important area for development and discovery of better diagnostic tools and new treatment modalities. Biobanks are developed in order to integrate the collection of clinical samples from both healthy individuals and patients and provide valuable information that will make possible improved patient care. Modern healthcare developments are intimately linked to information based on studies of patient samples from biobank archives in large scale studies. Today biobanks form important national, as well as international, networks that share and combine global resources. METHODS: We have developed and validated a novel biobanking workflow process that utilizes 384-tube systems with a high speed sample array robot with unique processing principles. RESULTS: The 384-tube format and robotic processing is incorporated into a cancer and cardiovascular diagnostic/prognostic research program with therapeutic interventions. Our biobank practice has gained acceptance within many hospitals and research units and is based on high-density sample storage with small aliquot sample volumes. The previous standard of 5-10 mL sample volume tubes is being replaced by smaller volumes of 50-70 MUL blood fractions that typically result in hundreds of thousands of aliquot fractions in 384-tube systems. CONCLUSIONS: Our novel biobanking workflow process is robust and well suited for clinical studies. PMID- 26272729 TI - Global tractography of multi-shell diffusion-weighted imaging data using a multi tissue model. AB - Diffusion-weighted imaging and tractography provide a unique, non-invasive technique to study the macroscopic structure and connectivity of brain white matter in vivo. Global tractography methods aim at reconstructing the full-brain fiber configuration that best explains the measured data, based on a generative signal model. In this work, we incorporate a multi-shell multi-tissue model based on spherical convolution, into a global tractography framework, which allows to deal with partial volume effects. The required tissue response functions can be estimated from and hence calibrated to the data. The resulting track reconstruction is quantitatively related to the apparent fiber density in the data. In addition, the fiber orientation distribution for white matter and the volume fractions of gray matter and cerebrospinal fluid are produced as ancillary results. Validation results on simulated data demonstrate that this data-driven approach improves over state-of-the-art streamline and global tracking methods, particularly in the valid connection rate. Results in human brain data correspond to known white matter anatomy and show improved modeling of partial voluming. This work is an important step toward detecting and quantifying white matter changes and connectivity in healthy subjects and patients. PMID- 26272730 TI - Simultaneous control of error rates in fMRI data analysis. AB - The key idea of statistical hypothesis testing is to fix, and thereby control, the Type I error (false positive) rate across samples of any size. Multiple comparisons inflate the global (family-wise) Type I error rate and the traditional solution to maintaining control of the error rate is to increase the local (comparison-wise) Type II error (false negative) rates. However, in the analysis of human brain imaging data, the number of comparisons is so large that this solution breaks down: the local Type II error rate ends up being so large that scientifically meaningful analysis is precluded. Here we propose a novel solution to this problem: allow the Type I error rate to converge to zero along with the Type II error rate. It works because when the Type I error rate per comparison is very small, the accumulation (or global) Type I error rate is also small. This solution is achieved by employing the likelihood paradigm, which uses likelihood ratios to measure the strength of evidence on a voxel-by-voxel basis. In this paper, we provide theoretical and empirical justification for a likelihood approach to the analysis of human brain imaging data. In addition, we present extensive simulations that show the likelihood approach is viable, leading to "cleaner"-looking brain maps and operational superiority (lower average error rate). Finally, we include a case study on cognitive control related activation in the prefrontal cortex of the human brain. PMID- 26272728 TI - Relevant feature set estimation with a knock-out strategy and random forests. AB - Group analysis of neuroimaging data is a vital tool for identifying anatomical and functional variations related to diseases as well as normal biological processes. The analyses are often performed on a large number of highly correlated measurements using a relatively smaller number of samples. Despite the correlation structure, the most widely used approach is to analyze the data using univariate methods followed by post-hoc corrections that try to account for the data's multivariate nature. Although widely used, this approach may fail to recover from the adverse effects of the initial analysis when local effects are not strong. Multivariate pattern analysis (MVPA) is a powerful alternative to the univariate approach for identifying relevant variations. Jointly analyzing all the measures, MVPA techniques can detect global effects even when individual local effects are too weak to detect with univariate analysis. Current approaches are successful in identifying variations that yield highly predictive and compact models. However, they suffer from lessened sensitivity and instabilities in identification of relevant variations. Furthermore, current methods' user-defined parameters are often unintuitive and difficult to determine. In this article, we propose a novel MVPA method for group analysis of high-dimensional data that overcomes the drawbacks of the current techniques. Our approach explicitly aims to identify all relevant variations using a "knock-out" strategy and the Random Forest algorithm. In evaluations with synthetic datasets the proposed method achieved substantially higher sensitivity and accuracy than the state-of-the-art MVPA methods, and outperformed the univariate approach when the effect size is low. In experiments with real datasets the proposed method identified regions beyond the univariate approach, while other MVPA methods failed to replicate the univariate results. More importantly, in a reproducibility study with the well known ADNI dataset the proposed method yielded higher stability and power than the univariate approach. PMID- 26272731 TI - Assessment of bleeding risk in patients with coronary artery disease on dual antiplatelet therapy. A systematic review. AB - Patients with coronary artery disease are usually treated with dual antiplatelet therapy (DAPT) after percutaneous coronary intervention. Patients on DAPT are at risk of both ischaemic and bleeding events. Although side-lined for a long time, real-life studies have shown that both the incidence and the associated morbidity and mortality of out-of-hospital bleeding are high. This indicates that prevention of (post-interventional) bleeding is as important as prevention of ischaemia. For this purpose it is crucial to reliably identify patients with a high bleeding risk. In order to postulate an algorithm, which could help identifying these patients, we performed a systematic review to determine the value of previously proposed prognostic modalities for bleeding. We searched and appraised the following tools: platelet function tests, genetic tests, bleeding scores and questionnaires and haemostatic tests. Most studies indicated that low on-treatment platelet reactivity (LTPR), as measured by several platelet function tests, and the carriage of CYP2C19*17 allele were independent risk factors for bleeding. A bleeding score also proved to be helpful in identifying patients at risk. No studies on haemostatic tests were retrieved. Several patient characteristics were also identified as independent predictors of bleeding, such as older age, female sex and renal failure. Combining these risk factors we propose an algorithm that would hypothetically facilitate identification of those patients at highest risk, warranting prevention measures for bleeding. This could be a starting point for further research concerning the topic. PMID- 26272732 TI - Adenosine A1-receptor blockade impairs the ability of rat pups to autoresuscitate from primary apnea during repeated exposure to hypoxia. AB - Failure of gasping to bring about autoresuscitation from hypoxia-induced apnea has been suggested to play a role in sudden unexpected infant death. Little is known, however, about factors that influence the ability of gasping to restore life during severe hypoxia in newborns. Given that adenosine modulates cardiac function during hypoxia-induced apnea and that cardiac dysfunction plays a role in mediating autoresuscitation failure, the present experiments were carried out on 34, 5- to 6-, and 10- to 11-day-old rat pups to investigate their ability to autoresuscitate from hypoxia-induced apnea during repeated exposure to hypoxia after adenosine A1-receptor blockade. Each pup was placed into a temperature controlled chamber regulated to 37 +/- 1 degrees C and repeatedly exposed to an anoxic gas mixture (97% N2 and 3% CO2) until the occurrence of autoresuscitation failure. One group was studied following administration of the selective adenosine A1-receptor antagonist 8-Cyclopentyl-1,3,-dipropylxanthine (DPCPX) and one group was studied following vehicle. DPCPX significantly attenuated bradycardia during hypoxia-induced apnea and impaired the ability of both age groups of pups to autoresuscitate during repeated exposure to hypoxia (5-6 days tolerated - vehicle 17 +/- 4 vs. DPCPX 10 +/- 2 hypoxia exposures [P < 0.05]; 10 11 days tolerated - vehicle 10 +/- 2 vs. DPCPX 7 +/- 2 hypoxia exposures [P < 0.05]). Death in all pups resulted from the inability of gasping to restore cardiovascular function during hypoxia-induced apnea although the mechanism of cardiovascular dysfunction/failure was influenced and the occurrence hastened by DPCPX. Thus, our data provide evidence that adenosine acting via adenosine A1 receptors enhances the ability of rat pups to tolerate repeated exposure to severe hypoxia during early postnatal maturation. PMID- 26272733 TI - The effect of training volume and intensity on improvements in muscular strength and size in resistance-trained men. AB - This investigation compared the effect of high-volume (VOL) versus high-intensity (INT) resistance training on stimulating changes in muscle size and strength in resistance-trained men. Following a 2-week preparatory phase, participants were randomly assigned to either a high-volume (VOL; n = 14, 4 * 10-12 repetitions with ~70% of one repetition maximum [1RM], 1-min rest intervals) or a high intensity (INT; n = 15, 4 * 3-5 repetitions with ~90% of 1RM, 3-min rest intervals) training group for 8 weeks. Pre- and posttraining assessments included lean tissue mass via dual energy x-ray absorptiometry, muscle cross-sectional area and thickness of the vastus lateralis (VL), rectus femoris (RF), pectoralis major, and triceps brachii muscles via ultrasound images, and 1RM strength in the back squat and bench press (BP) exercises. Blood samples were collected at baseline, immediately post, 30 min post, and 60 min postexercise at week 3 (WK3) and week 10 (WK10) to assess the serum testosterone, growth hormone (GH), insulin like growth factor-1 (IGF1), cortisol, and insulin concentrations. Compared to VOL, greater improvements (P < 0.05) in lean arm mass (5.2 +/- 2.9% vs. 2.2 +/- 5.6%) and 1RM BP (14.8 +/- 9.7% vs. 6.9 +/- 9.0%) were observed for INT. Compared to INT, area under the curve analysis revealed greater (P < 0.05) GH and cortisol responses for VOL at WK3 and cortisol only at WK10. Compared to WK3, the GH and cortisol responses were attenuated (P < 0.05) for VOL at WK10, while the IGF1 response was reduced (P < 0.05) for INT. It appears that high-intensity resistance training stimulates greater improvements in some measures of strength and hypertrophy in resistance-trained men during a short-term training period. PMID- 26272734 TI - Investigation of metabolic changes in STZ-induced diabetic rats with hyperpolarized [1-13C]acetate. AB - In the metabolism of acetate several enzymes are involved, which play an important role in free fatty acid oxidation. Fatty acid metabolism is altered in diabetes patients and therefore acetate might serve as a marker for pathological changes in the fuel selection of cells, as these changes occur in diabetes patients. Acetylcarnitine is a metabolic product of acetate, which enables its transport into the mitochondria for energy production. This study investigates whether the ratio of acetylcarnitine to acetate, measured by noninvasive hyperpolarized [1-(13)C]acetate magnetic resonance spectroscopy, could serve as a marker for myocardial, hepatic, and renal metabolic changes in rats with Streptozotocin (STZ)-induced diabetes in vivo. We demonstrate that the conversion of acetate to acetylcarnitine could be detected and quantified in all three organs of interest. More interestingly, we found that the hyperpolarized acetylcarnitine to acetate ratio was independent of blood glucose levels and prolonged hyperglycemia following diabetes induction in a type-1 diabetes model. PMID- 26272735 TI - Potentiation of cGMP signaling increases oxygen delivery and oxidative metabolism in contracting skeletal muscle of older but not young humans. AB - Aging is associated with progressive loss of cardiovascular and skeletal muscle function. The impairment in physical capacity with advancing age could be related to an insufficient peripheral O2 delivery to the exercising muscles. Furthermore, the mechanisms underlying an impaired blood flow regulation remain unresolved. Cyclic guanosine monophosphate (cGMP) is one of the main second messengers that mediate smooth muscle vasodilation and alterations in cGMP signaling could, therefore, be one mechanism by which skeletal muscle perfusion is impaired with advancing age. The current study aimed to evaluate the effect of inhibiting the main enzyme involved in cGMP degradation, phosphodiesterase 5 (PDE5), on blood flow and O2 delivery in contracting skeletal muscle of young and older humans. A group of young (23 +/- 1 years) and a group of older (72 +/- 2 years) male human subjects performed submaximal knee-extensor exercise in a control setting and following intake of the highly selective PDE5 inhibitor sildenafil. Sildenafil increased leg O2 delivery (6-9%) and leg O2 uptake (10-12%) at all three exercise intensities in older but not young subjects. The increase in leg O2 delivery with sildenafil in the older subjects correlated with the increase in leg O2 uptake (r (2) = 0.843). These findings suggest an insufficient O2 delivery to the contracting skeletal muscle of aged individuals and that reduced cGMP availability is a novel mechanism underlying impaired skeletal muscle perfusion with advancing age. PMID- 26272736 TI - CPM Test-Retest Reliability: "Standard" vs "Single Test-Stimulus" Protocols. AB - OBJECTIVES: Assessment of pain inhibitory mechanisms using conditioned pain modulation (CPM) is relevant clinically in prediction of pain and analgesic efficacy. Our objective is to provide necessary estimates of intersession CPM reliability, to enable transformation of the CPM paradigm into a clinical tool. DESIGN: Two cohorts of young healthy subjects (N = 65) participated in two dual session studies. In Study I, a Bath-Thermode CPM protocol was used, with hot water immersion and contact heat as conditioning- and test-stimuli, respectively, in a classical parallel CPM design introducing test-stimulus first, and then the conditioning- and repeated test-stimuli in parallel. Study II consisted of two CPM protocols: 1) Two-Thermodes, one for each of the stimuli, in the same parallel design as above, and 2) single test-stimulus (STS) protocol with a single administration of a contact heat test-stimulus, partially overlapped in time by a remote shorter contact heat as conditioning stimulus. Test-retest reliability was assessed within 3-7 days. RESULTS: The STS-CPM had superior reliability intraclass correlation (ICC2 ,: 1 = 0.59) over Bath-Thermode (ICC2 ,: 1 = 0.34) or Two-Thermodes (ICC2 ,: 1 = 0.21) protocols. The hand immersion conditioning pain had higher reliability than thermode pain (ICC2 ,: 1 = 0.76 vs ICC2 ,: 1 = 0.16). Conditioned test-stimulus pain scores were of good (ICC2 ,: 1 = 0.62) or fair (ICC2 ,: 1 = 0.43) reliability for the Bath-Thermode and the STS, respectively, but not for the Two-Thermodes protocol (ICC2 ,: 1 = 0.20). CONCLUSIONS: The newly developed STS-CPM paradigm was more reliable than other CPM protocols tested here, and should be further investigated for its clinical relevance. It appears that large contact size of the conditioning-stimulus and use of single rather than dual test-stimulus pain contribute to augmentation of CPM reliability. PMID- 26272738 TI - Erratum: Structural conservation among the rhodopsin-like and other G protein coupled receptors. PMID- 26272739 TI - Shortfalls of the use of HbA1C-derived eAG in older adults with diabetes. AB - AIMS: The hemoglobin HbA1C (HbA1C) value, translated into estimated average glucose concentration (eAG), is commonly used to assess glycaemic control and manage treatment regimens in people with diabetes. However, the relationships among HbA1C-derived eAG, and mean glucose concentration derived from continuous glucose monitoring (CGM) in different populations have not been well studied. We examined this relationship in older people with diabetes and compared the results to those currently used in clinical practice. METHODS: Data from three studies evaluating CGM in older adults (>=70 years of age), with stable glycaemic control were analyzed retrospectively. Mean glucose and mean amplitude of glucose excursion (MAGE) were calculated from CGM data and correlated with HbA1C and HbA1C-derived eAG using the ADAG study formula. RESULTS: HbA1C and CGM data were analyzed from 90 patients with mean age 76+/-5 years, HbA1C 7.9+/-1.2% (63+/-13 mmol/mol) and 77% with Type 2 diabetes. The HbA1C and HbA1C-derived eAG correlated significantly with CGM-measured mean glucose (r(2)=0.30, p<0.0001) and MAGE (r(2)=0.16, p=0.00013) in this population and all its subgroups, but the slopes of the relationship between HbA1C and eAG or CGM-measured mean glucose were significantly different. CONCLUSIONS: HbA1C-derived eAG values may not accurately reflect CGM-measured mean glucose or MAGE in older adults with diabetes. Wide glucose excursions should be considered and HbA1C should be interpreted cautiously when making treatment changes based on HbA1C. PMID- 26272737 TI - Characterization of STAT3 expression, signaling and inhibition in feline oral squamous cell carcinoma. AB - BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) plays a critical role in tumor development by regulating signaling pathways involved in cell proliferation, survival, metastasis and angiogenesis. STAT3 is activated in many cancers, including head and neck squamous cell carcinoma (HNSCC) in people. Feline oral squamous cell carcinoma (OSCC) is similar to advanced or recurrent HNSCC as it is poorly responsive to traditional therapies and carries a poor long term prognosis. The purpose of this study was to characterize expression and activation of STAT3 in feline OSCC cell lines and tumor samples and to investigate the biologic activity of a novel, allosteric STAT3 inhibitor, LLL12, in feline OSCC cell lines. RESULTS: We evaluated 3 feline OSCC cell lines and one of these (SCCF2) exhibited high levels of constitutive STAT3 phosphorylation and high sensitivity to LLL12 treatment. Exposure of SCCF2 cells to LLL12 resulted in decreased expression of pSTAT3 and total STAT3, apoptosis as assessed by caspase 3/7 activation, inhibition of colony formation and reduced expression of the STAT3 transcriptional target survivin. In contrast, the STAT3 transcriptional targets VEGF and MCL-1 increased after LLL12 treatment. This was, in part, likely due to LLL12 mediated upregulation of HIF-1alpha, which is known to drive VEGF and MCL-1 expression. The OSCC cell lines with low basal STAT3 phosphorylation did not exhibit these effects, suggesting that STAT3 inhibition was responsible for the observed results. Lastly, immunohistochemistry for pSTAT3 was performed using a feline OSCC tissue microarray, demonstrating expression in 48 % of samples tested. CONCLUSIONS: These data demonstrate that LLL12 has biologic activity against a feline OSCC cell line expressing pSTAT3 and that STAT3 represents a target for therapeutic intervention in this disease. However, given the up-regulation of several STAT3 transcriptional targets following treatment, further investigation of STAT3 and its related signaling pathways in OSCC is warranted. PMID- 26272740 TI - Electrodiagnostic testing in diabetic neuropathy: Which limb? AB - Electrodiagnosis of subclinical diabetic neuropathies by nerve conduction studies remains challenging. The question arises about which nerves should be tested and what the best electrodiagnostic protocol to make an early diagnosis of diabetic neuropathies would be. On the basis of our findings and other evidence, which highlighted the remarkable prevalence of electrophysiological abnormalities in nerve conduction studies of the upper limbs, often in the presence of normal lower limb conduction parameters, we suggest that both ulnar and median nerves, in their motor and sensitive component, should be the two target nerves for electrodiagnostic protocols in diabetic neuropathies. PMID- 26272741 TI - Sudden cardiac and sudden unexpected death related to antipsychotics: A meta analysis of observational studies. AB - To estimate the risk of sudden cardiac death (SCD) or sudden unexpected death (SUD) related to individual antipsychotics, a meta-analysis of observational studies was performed. Adjusted odds ratio (OR) of SCD/SUD with 95% confidence intervals (CI) were extracted and pooled; heterogeneity was studied using Q statistic and I(2) index, and its potential causes (e.g., hERG blockade potency) explored using meta-regression. Two cohort (740,306 person-years) and four case control (2,557 cases; 17,670 controls) studies, investigating nine antipsychotics, were included. Compared with nonusers, the risk was increased for quetiapine (OR = 1.72, 95% CI: 1.33-2.23), olanzapine (OR = 2.04, 1.52-2.74), risperidone (OR = 3.04, 2.39-3.86), haloperidol (OR = 2.97, 1.59-5.54), clozapine (OR = 3.67, 1.94-6.94), and thioridazine (OR = 4.58, 2.09-10.05). Heterogeneity was found (Q = 20.0, P = 0.01; I(2) = 60.0%), and the increasing mean hERG blockade potency (P = 0.01) accounted for 43% of this. The SCD/SUD risk differed between individual antipsychotics, and mean hERG blockade potency could be an explanatory factor. This should be considered when initiating antipsychotic treatment. PMID- 26272742 TI - Exploring the relationship between anaesthesiologists' non-technical and technical skills. AB - BACKGROUND: A combination of non-technical skills (NTS) and technical skills (TS) is crucial for anaesthetic patient management. However, a deeper understanding of the relationship between these two skills remains to be explored. We investigated the characteristics of trainee anaesthesiologists' NTS and TS in a simulated unexpected difficult airway management scenario. METHODS: A mixed-method approach was used to explore the relationship between NTS and TS in 25 videos of 2nd year trainee anaesthesiologists managing a simulated difficult airway scenario. The videos were assessed using the customised version of the Anaesthetists' Non Technical Skills System, ANTSdk, and an adapted TS checklist for calculating the correlation between NTS and TS. Written descriptions of the observed NTS were analysed using directed content analysis. RESULTS: The correlation between the NTS and the TS ratings was 0.106 (two-tailed significance of 0.613). Inter-rater reliability was substantial. Themes characterising good NTS included a systematic approach, planning and communicating decisions as well as responding to the evolving situation. A list of desirable, concrete NTS for the specific airway management situation was generated. CONCLUSION: This study illustrates that anaesthesiologist trainees' NTS and TS were not correlated in this setting, but rather intertwined and how the interplay of NTS and TS can impact patient management. Themes describing the characteristics of NTS and a list of desirable, concrete NTS were developed to aid the understanding, training and use of NTS. PMID- 26272743 TI - Recurrence and survival among breast cancer patients achieving a pathological complete response to neoadjuvant chemotherapy. AB - Patients who achieve a pathological complete response (pCR) after neoadjuvant therapy, including chemotherapy with or without trastuzumab (NAT) have better outcomes than patients with residual disease. Despite the excellent prognosis associated with achieving a pCR, tumors still recur. The objective of this study was to evaluate factors associated with tumor recurrence and survival among patients achieving pCR after NAT. We identified 749 patients with primary breast cancer who achieved pCR after NAT between 1988 and 2009. pCR was defined as no evidence of invasive cancer in the breast and ipsilateral axillary lymph nodes on pathological evaluation. The Kaplan-Meier product limit method and multivariate Cox proportional hazards models were used to determine the association between clinical and demographic factors and outcomes. Median follow-up was 35 months (range, 1-258 months). Overall 5-year distant metastasis-free survival was 93% (95% confidence interval [CI], 90-95%) and 5-year overall survival (OS) was 96% (95% CI, 93-97%). In the multivariable model, we observed that patients >50 years had significantly decreased risk of distant metastasis (hazard ratio [HR] 0.47; 95% CI, 0.22-0.98) and that patients with clinical stage at diagnosis IIIB-C cancer had both an increased risk of distant metastasis (HR 3.92; 95% CI, 1.54 10.00) and lower OS (HR 4.75; 95% CI, 1.60-14.08). Patients with pCR after NAT have excellent outcomes. However, our data show that younger patient and those with clinical stage at diagnosis IIIB and IIIC cancers are at increased risk of developing distant metastasis. PMID- 26272744 TI - Association between Met-BDNF allele and vulnerability to paclitaxel-induced peripheral neuropathy. PMID- 26272745 TI - The Steroid Hormone 20-Hydroxyecdysone Up-regulates Ste-20 Family Serine/Threonine Kinase Hippo to Induce Programmed Cell Death. AB - The steroid hormone 20-hydroxyecdysone (20E) and the serine/threonine Ste20-like kinase Hippo signal promote programmed cell death (PCD) during development, although the interaction between them remains unclear. Here, we present evidence that 20E up-regulates Hippo to induce PCD during the metamorphic development of insects. We found that Hippo is involved in 20E-induced metamorphosis via promoting the phosphorylation and cytoplasmic retention of Yorkie (Yki), causing suppressed expression of the inhibitor of apoptosis (IAP), thereby releasing its inhibitory effect on caspase. Furthermore, we show that 20E induced the expression of Hippo at the transcriptional level through the ecdysone receptor (EcR), ultraspiracle protein (USP), and hormone receptor 3 (HR3). We also found that Hippo suppresses the binding of Yki complex to the HR3 promoter. In summary, 20E up-regulates the transcription of Hippo via EcRB1, USP1, and HR3 to induce PCD, and Hippo has negative feedback effects on HR3 expression. These two signaling pathways coordinate PCD during insect metamorphosis. PMID- 26272748 TI - Transmitting information of an object behind the obstacle to infinity. AB - We propose an illusion device that transforms a metallic cylinder into a Luneburg lens by using transformation optics. Such a transformed focusing lens guides electromagnetic waves to propagate around the central metallic cylinder smoothly and be focused on one spot, and thus the information of an object behind the obstacle can be transmitted to infinity. In order to realize the required anisotropic parameters with high permittivity and low permeability, we design embedded split-ring resonators (SRRs) to increase the permittivity of the traditional SRR structures. In experiments, we fabricate and measure the transformed lens, and the tested results agree well with the numerical simulations and theoretical predictions. The proposed transformation lens can mimic some properties of Einstein gravitational lens because their wave propagation behaviors are very similar. PMID- 26272749 TI - The health-seeking behaviours of first-time mothers with persistent pelvic girdle pain after childbirth in Ireland: A descriptive qualitative study. AB - OBJECTIVE: to explore the health-seeking behaviours of primiparous women with pelvic girdle pain persisting for more than three months post partum. DESIGN: a descriptive qualitative design involving face-to-face semi-structured interviews following institutional ethical approval. Transcripts were analysed using thematic analysis. SETTING: an urban hospital in Ireland. PARTICIPANTS: a purposive sample of 23 consenting first-time mothers with pelvic girdle pain persisting for at least three months post partum. FINDINGS: 'they didn't ask, I didn't tell' was a key theme, which included emerging categories of a perceived lack of follow-up post partum, and feeling ignored by healthcare professionals. The theme 'Seeking advice and support' describes women's role of talking to others, and triggers and barriers to getting help. 'Coping strategies' was the third theme emerging from the interviews, whereby participants described different strategies they used to deal with their symptoms, although many expressed uncertainty about what to do or who to see. CONCLUSION AND IMPLICATIONS FOR PRACTICE: our findings show the importance of appropriate information and follow-up care for women with pelvic girdle pain and highlight barriers they encounter in seeking help. They also question the duration of postnatal care as participants felt that postnatal care was stopped too early. The findings may assist maternity care providers in addressing mothers' expectations and needs related to persistent pelvic girdle pain. PMID- 26272746 TI - Allosteric Activation of Bacterial Swi2/Snf2 (Switch/Sucrose Non-fermentable) Protein RapA by RNA Polymerase: BIOCHEMICAL AND STRUCTURAL STUDIES. AB - Members of the Swi2/Snf2 (switch/sucrose non-fermentable) family depend on their ATPase activity to mobilize nucleic acid-protein complexes for gene expression. In bacteria, RapA is an RNA polymerase (RNAP)-associated Swi2/Snf2 protein that mediates RNAP recycling during transcription. It is known that the ATPase activity of RapA is stimulated by its interaction with RNAP. It is not known, however, how the RapA-RNAP interaction activates the enzyme. Previously, we determined the crystal structure of RapA. The structure revealed the dynamic nature of its N-terminal domain (Ntd), which prompted us to elucidate the solution structure and activity of both the full-length protein and its Ntd truncated mutant (RapADeltaN). Here, we report the ATPase activity of RapA and RapADeltaN in the absence or presence of RNAP and the solution structures of RapA and RapADeltaN either ligand-free or in complex with RNAP. Determined by small angle x-ray scattering, the solution structures reveal a new conformation of RapA, define the binding mode and binding site of RapA on RNAP, and show that the binding sites of RapA and sigma(70) on the surface of RNAP largely overlap. We conclude that the ATPase activity of RapA is inhibited by its Ntd but stimulated by RNAP in an allosteric fashion and that the conformational changes of RapA and its interaction with RNAP are essential for RNAP recycling. These and previous findings outline the functional cycle of RapA, which increases our understanding of the mechanism and regulation of Swi2/Snf2 proteins in general and of RapA in particular. The new structural information also leads to a hypothetical model of RapA in complex with RNAP immobilized during transcription. PMID- 26272747 TI - Genome-wide Mechanosensitive MicroRNA (MechanomiR) Screen Uncovers Dysregulation of Their Regulatory Networks in the mdm Mouse Model of Muscular Dystrophy. AB - Muscular dystrophies (MDs) are a heterogeneous group of genetic and neuromuscular disorders, which result in severe loss of motor ability and skeletal muscle mass and function. Aberrant mechanotransduction and dysregulated-microRNA pathways are often associated with the progression of MD. Here, we hypothesized that dysregulation of mechanosensitive microRNAs (mechanomiRs) in dystrophic skeletal muscle plays a major role in the progression of MD. To test our hypothesis, we performed a genome-wide expression profile of anisotropically regulated mechanomiRs and bioinformatically analyzed their target gene networks. We assessed their functional roles in the advancement of MD using diaphragm muscles from mdm (MD with myositis) mice, an animal model of human tibial MD (titinopathy), and their wild-type littermates. We were able to show that ex vivo anisotropic mechanical stretch significantly alters the miRNA expression profile in diaphragm muscles from WT and mdm mice; as a result, some of the genes associated with MDs are dysregulated in mdm mice due to differential regulation of a distinct set of mechanomiRs. Interestingly, we found a contrasting expression pattern of the highly expressed let-7 family mechanomiRs, let-7e-5p and miR-98-5p, and their target genes associated with the extracellular matrix and TGF-beta pathways, respectively, between WT and mdm mice. Gain- and loss-of function analysis of let-7e-5p in myocytes isolated from the diaphragms of WT and mdm mice confirmed Col1a1, Col1a2, Col3a1, Col24a1, Col27a1, Itga1, Itga4, Scd1, and Thbs1 as target genes of let-7e-5p. Furthermore, we found that miR-98 negatively regulates myoblast differentiation. Our study therefore introduces additional biological players in the regulation of skeletal muscle structure and myogenesis that may contribute to unexplained disorders of MD. PMID- 26272751 TI - RNA transcripts for the quantification of differentiation allow marked improvements in the performance of embryonic stem cell test (EST). AB - Embryonic stem cell test (EST) is an in vitro validated assay for testing embryotoxicity. The EST needs improvements before being used for regulatory purposes, but also needs technical simplification for use in high throughput screenings. We propose the quantification in alterations of the differentiation of D3 monolayer cells cultures through the expression of biomarker genes in a shorter (5-day) and technically simpler (we use only monolayer cultures) test. We have defined a set of sixteen different genes biomarkers of ectoderm (Nrcam, Nes, Shh and Pnpla6), endoderm formation (Flk1 and Afp), mesoderm formation (Mesp1, Vegfa, Myo1e and Hdac7) and general cellular processes (Cdk1, Myc, Jun, Mixl, Cer and Wnt3). These, together with alterations in the viability of D3 and 3T3 cells and the prediction model of a classic EST, enhance the features of EST determinations to 100% concordance between in vivo-in vitro predictions with a set of seven different chemicals used in the validation of a classic EST. In conclusion, the proposed changes implemented in the classic EST confer it more reliability, speed and technical simplicity, which brings the EST closer to high throughput processes and regulatory purposes. PMID- 26272750 TI - Artificial biofilms establish the role of matrix interactions in staphylococcal biofilm assembly and disassembly. AB - We demonstrate that the microstructural and mechanical properties of bacterial biofilms can be created through colloidal self-assembly of cells and polymers, and thereby link the complex material properties of biofilms to well understood colloidal and polymeric behaviors. This finding is applied to soften and disassemble staphylococcal biofilms through pH changes. Bacterial biofilms are viscoelastic, structured communities of cells encapsulated in an extracellular polymeric substance (EPS) comprised of polysaccharides, proteins, and DNA. Although the identity and abundance of EPS macromolecules are known, how these matrix materials interact with themselves and bacterial cells to generate biofilm morphology and mechanics is not understood. Here, we find that the colloidal self assembly of Staphylococcus epidermidis RP62A cells and polysaccharides into viscoelastic biofilms is driven by thermodynamic phase instability of EPS. pH conditions that induce phase instability of chitosan produce artificial S. epidermidis biofilms whose mechanics match natural S. epidermidis biofilms. Furthermore, pH-induced solubilization of the matrix triggers disassembly in both artificial and natural S. epidermidis biofilms. This pH-induced disassembly occurs in biofilms formed by five additional staphylococcal strains, including three clinical isolates. Our findings suggest that colloidal self-assembly of cells and matrix polymers produces biofilm viscoelasticity and that biofilm control strategies can exploit this mechanism. PMID- 26272752 TI - Elimination kinetics and molecular reaction mechanisms of cyclosarin (GF) by an oxime substituted beta-cyclodextrin derivative in vitro. AB - Detoxification mechanisms of the chemical warfare agent cyclosarin (GF) in presence of 6-OxP-CD were investigated in detail in in vitro model systems. Most important finding was the preference of 6-Ox-P-CD to eliminate the more toxic (-) GF. However, elimination of GF enantiomers was dependent on the 6-OxP-CD:GF ratios showing decreasing stereoselectivity and speed of the reaction with increasing GF concentrations. Formation of covalent mono, bis, tris and tetrakis conjugates ((CHMP)n-6-OxP-CD) and appearance of small molecular fragments (SMF) as possible decomposition products after consumption of 6-OxP-CD could be observed.. Interestingly, the non-toxic metabolite O-cyclohexyl methylphosphonic acid (CHMPA) and covalent mono and bis conjugates of 6-OxP-CD and GF were immediately formed, indicating that GF elimination proceeds along different pathways. These important new insights provide information about the mode of action of 6-Ox-P-CD including the role of the pyridinium aldoxime group on the cyclodextrin ring. They are the basis for further investigations in biological media, which could eventually lead to approval of 6-OxP-CD as a new antidote against nerve agent toxicity. PMID- 26272754 TI - Heparin/heparan sulfates bind to and modulate neuronal L-type (Cav1.2) voltage dependent Ca(2+) channels. AB - Our previous studies revealed that L-type voltage-dependent Ca(2+) channels (Cav1.2 L-VDCCs) are modulated by the neural extracellular matrix backbone, polyanionic glycan hyaluronic acid. Here we used isothermal titration calorimetry and screened a set of peptides derived from the extracellular domains of Cav1.2alpha1 to identify putative binding sites between the channel and hyaluronic acid or another class of polyanionic glycans, such as heparin/heparan sulfates. None of the tested peptides showed detectable interaction with hyaluronic acid, but two peptides derived from the first pore-forming domain of Cav1.2alpha1 subunit bound to heparin. At 25 degrees C the binding of the peptide P7 (MGKMHKTCYN) was at ~50 MUM, and that of the peptide P8 (GHGRQCQNGTVCKPGWDGPKHG) was at ~21 MUM. The Cav1.2alpha1 first pore forming segment that contained both peptides maintained a high affinity for heparin (~23 MUM), integrating their enthalpic and entropic binding contributions. Interaction between heparin and recombinant as well as native full-length neuronal Cav1.2alpha1 channels was confirmed using the heparin-agarose pull down assay. Whole cell patch clamp recordings in HEK293 cells transfected with neuronal Cav1.2 channels revealed that enzymatic digestion of highly sulfated heparan sulfates with heparinase 1 affects neither voltage-dependence of channel activation nor the level of steady state inactivation, but did speed up channel inactivation. Treatment of hippocampal cultures with heparinase 1 reduced the firing rate and led to appearance of long-lasting bursts in the same manner as treatment with the inhibitor of L-VDCC diltiazem. Thus, heparan sulfate proteoglycans may bind to and regulate L-VDCC inactivation and network activity. PMID- 26272755 TI - TRPM4 in cardiac electrical activity. AB - TRPM4 forms a non-selective cation channel activated by internal Ca(2+). Its functional expression was demonstrated in cardiomyocytes of several mammalian species including humans, but the channel is also present in many other tissues. The recent characterization of the TRPM4 inhibitor 9-phenanthrol, and the availability of transgenic mice have helped to clarify the role of TRPM4 in cardiac electrical activity, including diastolic depolarization from the sino atrial node cells in mouse, rat, and rabbit, as well as action potential duration in mouse cardiomyocytes. In rat and mouse, pharmacological inhibition of TRPM4 prevents cardiac ischaemia-reperfusion injuries and decreases the occurrence of arrhythmias. Several studies have identified TRPM4 mutations in patients with inherited cardiac diseases including conduction blocks and Brugada syndrome. This review identifies TRPM4 as a significant actor in cardiac electrophysiology. PMID- 26272756 TI - Endothelial Galphaq/11 is required for VEGF-induced vascular permeability and angiogenesis. AB - AIMS: VEGF A (VEGF-A) is a central regulator of pre- and postnatal vascular development. In vitro studies suggested that heterotrimeric G-proteins of the Gq/11 family contribute to VEGF receptor 2 (VEGFR2) signalling, but the mechanism and physiological relevance of this finding is unknown. The aim of this study is to understand the role of endothelial Galphaq/11 in VEGF-dependent regulation of vascular permeability and angiogenesis. METHODS AND RESULTS: We show here that VEGF-A-induced signalling events, such as VEGFR2 autophosphorylation, calcium mobilization, or phosphorylation of Src and Cdh5, were reduced in Galphaq/11 deficient endothelial cells (ECs), resulting in impaired VEGF-dependent barrier opening, tube formation, and proliferation. Agonists at Gq/11-coupled receptors facilitated VEGF-A-induced VEGFR2 autophosphorylation in a Galphaq/11-dependent manner, thereby enhancing downstream VEGFR2 signalling. In vivo, EC-specific Galphaq/11- and Galphaq-deficient mice showed reduced VEGF-induced fluid extravasation, and retinal angiogenesis was significantly impaired. Galphaq deficient ECs showed reduced proliferation, Cdh5 phosphorylation, and fluid extravasation, whereas apoptosis was increased. CONCLUSION: Galphaq/11 critically contributes to VEGF-A-dependent permeability control and angiogenic behaviour in vitro and in vivo. PMID- 26272753 TI - Activation of glucocorticoid receptors in Muller glia is protective to retinal neurons and suppresses microglial reactivity. AB - Reactive microglia and macrophages are prevalent in damaged retinas. Glucocorticoid signaling is known to suppress inflammation and the reactivity of microglia and macrophages. In the vertebrate retina, the glucocorticoid receptor (GCR) is known to be activated and localized to the nuclei of Muller glia (Gallina et al., 2014). Accordingly, we investigated how signaling through GCR influences the survival of neurons using the chick retina in vivo as a model system. We applied intraocular injections of GCR agonist or antagonist, assessed microglial reactivity, and the survival of retinal neurons following different damage paradigms. Microglial reactivity was increased in retinas from eyes that were injected with vehicle, and this reactivity was decreased by GCR-agonist dexamethasone (Dex) and increased by GCR-antagonist RU486. We found that activation of GCR suppresses the reactivity of microglia and inhibited the loss of retinal neurons resulting from excitotoxicity. We provide evidence that the protection-promoting effects of Dex were maintained when the microglia were selectively ablated. Similarly, intraocular injections of Dex protected ganglion cells from colchicine-treatment and protected photoreceptors from damage caused by retinal detachment. We conclude that activation of GCR promotes the survival of ganglion cells in colchicine-damaged retinas, promotes the survival of amacrine and bipolar cells in excitotoxin-damaged retinas, and promotes the survival of photoreceptors in detached retinas. We propose that suppression of microglial reactivity is secondary to activation of GCR in Muller glia, and this mode of signaling is an effective means to lessen the damage and vision loss resulting from different types of retinal damage. PMID- 26272758 TI - A cross-cultural perspective on aging and memory: Comparisons between Bangladesh and Sweden. AB - Most studies on cognitive aging have been conducted in high-income countries (mainly on Western populations). The main aim of this study was to compare the relative importance of predictors of episodic and semantic memory performance in older people (>=60 years) from Bangladesh (n = 400) and Sweden (n = 1,098). Hierarchical regression models were used in order to study the importance of some commonly used predictors in the two countries. A main finding was that variations in age did not have much impact on episodic and semantic memory performance in Bangladesh. Instead, sex was a strong predictor for semantic memory performance. In Sweden this pattern was reversed. In the Western world, chronological age is believed to be strongly associated with memory performance in cross-sectional studies, particularly in people greater than 60 years of age. This study indicates that the difference between the two countries (in relative importance of the predictors included in this study) is mainly due to the fact that years of education is connected to age in the Western world but to sex in Bangladesh. It remains to be examined whether earlier selective survival is also responsible for the relative absence of cognitive age differences in Bangladesh. PMID- 26272757 TI - The phospholipid-binding protein SESTD1 negatively regulates dendritic spine density by interfering with Rac1-Trio8 signaling pathway. AB - Dendritic spines are actin-rich protrusions from neuronal dendrites that harbor the majority of excitatory synapses. The balance of spine formation and retraction may influence dendritic integrity. While knowledge of the molecular mechanisms that promote dendritic spine formation has accumulated, little is known about the factors that limit spine formation. Here, we show that SESTD1, a phospholipid-binding protein containing a lipid-binding SEC14-like domain and two spectrin-repeat cytoskeleton interaction domains, negatively regulates dendritic spine density in cultured hippocampal neurons. Overexpression of SESTD1 decreases dendritic spine density in neurons by interfering with the interaction between Rac1 and its guanine nucleotide exchange factor (GEF) Trio8. Conversely, knockdown of SESTD1 increases dendritic spine density. Further analysis reveals that the SPEC1 domain-mediated interaction with Rac1 is required for SESTD1 activity toward a decrease in dendritic spine density. Transfection of GEF domain of Trio8 into neurons rescues SESTD1-mediated decrease in dendritic spine density. More importantly, overexpression of SESTD1 results in a decrease in the frequency of miniature excitatory postsynaptic currents (mEPSCs), whereas SESTD1 knockdown increases the mEPSC frequency. These results suggest that SESTD1 may act as a negative regulator of the Rac1-Trio8 signaling pathway to reduce dendritic spine density and lower excitatory synaptic transmission in hippocampal neurons. PMID- 26272759 TI - View combination in recognition of 3-D virtual reality layouts. AB - We investigated whether a normalization model or view combination model fit the performance of scene recognition of 3-D layouts using a virtual-reality paradigm. Participants learned a layout of seven objects from two training views (e.g., 0 degrees and 48 degrees ) by discriminating the "correct" layout from distracters. Later, they performed a discrimination task using the training views (e.g., 0 degrees and 48 degrees ), an interpolated view (e.g., 24 degrees ), an extrapolated view (e.g., 72 degrees ), and a far view (e.g., 96 degrees ). The results showed that the interpolated view was easier to discriminate than the extrapolated view and even easier than the training views. These results extend the applicability of view combination accounts of recognition to 3-D stimuli with stereoscopic depth information. PMID- 26272760 TI - Pathways to hostile collective action: The roles of general attitudes toward the advantaged group and situational anger. AB - Collective action is a group behavior that aims to improve the status, power, or influence of an entire group. The present study focused on hostile collective action performed for releasing negative emotions, and explored a pathway including the roles of general attitudes toward the advantaged group and situational group-based anger in predicting the disadvantaged groups' hostile collective action. Group-level data were collected via a laboratory experiment. The results obtained using multiple regression analysis suggested that general attitudes toward the advantaged group formed before the trigger event predicted hostile collective action indirectly through the mediating effects of situational group-based anger and collective action tendencies, which were both produced after that trigger event. In addition, situational group-based anger predicted hostile collective action fully through collective action tendencies. These pathways provided a continuous process of hostile collective action in which general attitudes toward the advantaged group that were formed before the trigger events would influence situational group-based anger when the trigger events occurred, and then affected hostile collective action for responding to these events. Thus, hostile collective action could be predicted before the trigger events by monitoring the disadvantaged groups' attitudes toward the advantaged group. Moreover, reducing destructive collective action by improving intergroup attitudes through some effective interventions was discussed in this study. PMID- 26272761 TI - Neural bases for basic processes in heuristic problem solving: Take solving Sudoku puzzles as an example. AB - Newell and Simon postulated that the basic steps in human problem-solving involve iteratively applying operators to transform the state of the problem to eventually achieve a goal. To check the neural basis of this framework, the present study focused on the basic processes in human heuristic problem-solving that the participants identified the current problem state and then recalled and applied the corresponding heuristic rules to change the problem state. A new paradigm, solving simplified Sudoku puzzles, was developed for an event-related functional magnetic resonance imaging (fMRI) study in problem solving. Regions of interest (ROIs), including the left prefrontal cortex, the bilateral posterior parietal cortex, the anterior cingulated cortex, the bilateral caudate nuclei, the bilateral fusiform, as well as the bilateral frontal eye fields, were found to be involved in the task. To obtain convergent evidence, in addition to traditional statistical analysis, we used the multivariate voxel classification method to check the accuracy of the predictions for the condition of the task from the blood oxygen level dependent (BOLD) response of the ROIs, using a new classifier developed in this study for fMRI data. To reveal the roles that the ROIs play in problem solving, we developed an ACT-R computational model of the information-processing processes in human problem solving, and tried to predict the BOLD response of the ROIs from the task. Advances in human problem-solving research after Newell and Simon are then briefly discussed. PMID- 26272762 TI - Empathy, emotional contagion, and rapid facial reactions to angry and happy facial expressions. AB - The aim was to explore whether emotional empathy is related to the capacity to react with rapid facial reactions to facial expressions of emotion, and if emotional empathy is related to the ability to experience a similar emotion as expressed by another person. People high or low in emotional empathy were exposed to pictures of happy and angry faces while their facial electromyography from the zygomaticus major and corrugator supercilii muscle regions was detected. High empathy participants rapidly reacted with larger zygomatic muscle activity to happy as compared with angry faces as early as after 500 ms after stimulus onset, and with larger corrugator muscle activity to angry than to happy faces after 500 ms. Accordingly, this group also reacted with a corresponding experience of emotion. The low empathy participants, in contrast, did not differentiate between the happy and angry stimuli with either facial muscles or in their self experience of emotion. The findings are related to the facial feedback hypothesis and the results are interpreted as support for the hypothesis that rapid and automatically evoked facial mimicry may be one important mechanism for emotional and empathic contagion to occur. PMID- 26272763 TI - Eye movement control in reading: Logographic Chinese versus alphabetic scripts. AB - Eye tracking is widely used to study the reading process in different languages. Given the unique properties of written Chinese, it is important to identify the similarities and differences in eye-movement controls between readers of Chinese and alphabetic scripts. In this article, we review the data available for comparison in four domains: (a) the perceptual span, (b) parafoveal processing, (c) the basic encoding unit, and (d) computer modeling. Our review indicates that, while some aspects of eye movement control in reading appear to be universal (e.g., the availability of orthographic information in the parafoveal preview), others are more script-specific (e.g., the size of the perceptual span). It is concluded that the study of cross-language differences is important for the development of reading models that are generalizable across readers of different scripts. PMID- 26272764 TI - Hyperbranched-hyperbranched polymeric nanoassembly to mediate controllable co delivery of siRNA and drug for synergistic tumor therapy. AB - This study reported a flexible nanoplatform constructed on the pH-dependent self assembly of two kinds of hyperbranched polymers, and then validated its potency as the controllable siRNA/drug co-delivery vehicle for the combination of chemotherapy with RNA interfering (RNAi) therapy. By virtue of pH-reversible phenylboronate linking, phenylboronic acid-tethered hyperbranched oligoethylenimine (OEI600-PBA) and 1,3-diol-rich hyperbranched polyglycerol (HBPO) can be spontaneously interlinked together into a core-corona nanoconstruction. The special buildup of compactly clustering OEI600-PBA units around hydrophobic HBPO aggregate offered significant advantages over parent OEI600-PBA, including strengthened affinity to siRNA, ability of further loading anticancer drug, easier cellular transport, and acidity-responsive release of payloads. To evaluate the co-delivery capability, Beclin1 siRNA and antitumor DOX were used as the therapeutic models in order to suppress the post-chemotherapy survival of tumor cells caused by drug-induced autophagy. The nanoassembly mediated single delivery of DOX displayed even better anticancer effects than free DOX, demonstrating the superiority of our pH-responsive nano-design. The nanoassembly-mediated co-delivery of siRNA together with DOX can effectively silence Beclin1 gene, suppress DOX-induced autophagy, and consequently provide strong synergism with a significant enhancement of cell-killing effects in cultured cancerous cells. The in vivo combinational treatment was shown to make the tumor more sensitive to DOX chemotherapy while displaying substantially improved safety as compared with the monochemotherapy. PMID- 26272766 TI - Exposure of haptic of posterior chamber intraocular lens after sutureless intrascleral fixation. AB - BACKGROUND: A technique of sutureless intrascleral fixation of an intraocular lens (IOL) in an eye that lacks a posterior capsular support has been reported. The advantage of this technique was that the suture-related complications did not develop. However, the long-term complications of a sutureless IOL implantation have not been reported. CASE PRESENTATION: A 75-years-old man had a sutureless intrascleral fixation (Y-fixation) of an IOL 4 months before our examination. The nasal haptic became exposed and the temporal haptic was seen in the subconjunctiva. The tilted IOL was removed and replaced by a posterior chamber IOL that was sutured to the sclera. At the 6 months examination, the eye was quiet and the IOL was stable. CONCLUSION: We suggest that the exposure of the nasal haptic of an IOL that was implanted by sutureless intrascleral fixation (Y fixation) was due to poor surgical technique and/or the erosion of a fragile sclera. Thus, eyes should be carefully and frequently monitored after sutureless intrascleral posterior chamber IOL implantation. PMID- 26272765 TI - Paclitaxel tumor priming promotes delivery and transfection of intravenous lipid siRNA in pancreatic tumors. AB - The major barrier for using small interfering RNA (siRNA) as cancer therapeutics is the inadequate delivery and transfection in solid tumors. We have previously shown that paclitaxel tumor priming, by inducing apoptosis, expands the tumor interstitial space, improves the penetration and dispersion of nanoparticles and siRNA-lipoplexes in 3-dimensional tumor histocultures, and promotes the delivery and transfection efficiency of siRNA-lipoplexes under the locoregional setting in vivo (i.e., intraperitoneal treatment of intraperitoneal tumors). The current study evaluated whether tumor priming is functional for systemically delivered siRNA via intravenous injection, which would subject siRNA to several additional delivery barriers and elimination processes. We used the same pegylated cationic (PCat)-siRNA lipoplexes as in the intraperitoneal study to treat mice bearing subcutaneous human pancreatic Hs766T xenograft tumors. The target gene was survivin, an inducible chemoresistance gene. The results show single agent paclitaxel delayed tumor growth but also significantly induced the survivin protein level in residual tumors, whereas addition of PCat-siSurvivin completely reversed the paclitaxel-induced survivin and enhanced the paclitaxel activity (p<0.05). In comparison, PCat-siSurvivin alone did not yield survivin knockdown or antitumor activity, indicating the in vivo effectiveness of intravenous siRNA mediated gene silencing requires paclitaxel cotreatment. Additional in vitro studies showed that paclitaxel promoted the cytoplasmic release of siGLO, a 22 nucleotide double-stranded RNA that has no mRNA targets, from its PCat lipoplex and/or endosomes/lysosomes. Taken together, our earlier and current data show paclitaxel tumor priming, by promoting the interstitial transport and cytoplasmic release, is critical to promote the delivery and transfection of siRNA in vivo. In addition, because paclitaxel has broad spectrum activity and is used to treat multiple types of solid tumors including the hard-to-treat pancreatic cancer, the synergistic paclitaxel+siSurvivin combination represents a potentially useful chemo-gene therapy. PMID- 26272767 TI - Relationship between swallowing function and the skeletal muscle mass of older adults requiring long-term care. AB - AIM: The present study investigated the risk factors for dysphagia among older adults who require long-term care, and also examined their systemic decrease in skeletal muscle mass. METHODS: We evaluated 399 people who required long-term care and who were residing in Omori town, Yokote city, Akita prefecture, Japan. We then analyzed data from 255 participants who had complete information available regarding their sex, age, case history (stroke, Parkinson's disease and dementia), Barthel Index, Skeletal Muscle Mass Index, oral function test and modified water swallowing test results. Participants' water swallowing test results were used to create groups with good or poor swallowing function, and a univariate analysis was carried out for each parameter. Parameters with a P-value of <0.25 in the univariate analysis were subsequently included in a multiple logistic regression model as explanatory variables, and good or poor swallowing function were defined as the dependent variables. RESULTS: After adjusting for age and sex, our analysis showed that poor tongue motility (odds ratio 17.23, 95% confidence interval 5.90-50.31, P < 0.001) and decreased Skeletal Muscle Mass Index (odds ratio 3.36, 95% confidence interval 1.41-7.99, P = 0.006) were significantly correlated with decreased swallowing function. CONCLUSIONS: Decreased swallowing function was closely correlated with poor tongue motility, and this finding is similar to those of previous studies. However, the present results also show that decreased Skeletal Muscle Mass Index is a novel risk factor for dysphagia among older adults who require long-term care. PMID- 26272768 TI - Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of moderately emetogenic chemotherapy or anthracycline and cyclophosphamide regimens in patients with cancer: a randomised, active-controlled, double-blind, phase 3 trial. AB - BACKGROUND: Chemotherapy-induced nausea and vomiting is a common side-effect of many antineoplastic regimens and can occur for several days after treatment. We aimed to assess the neurokinin-1 receptor antagonist rolapitant, in combination with a serotonin (5-HT3) receptor antagonist and dexamethasone, for the prevention of chemotherapy-induced nausea and vomiting in patients with cancer after administration of moderately emetogenic chemotherapy or regimens containing an anthracycline and cyclophosphamide. METHODS: We conducted a global, randomised, double-blind, active-controlled, phase 3 study at 170 cancer centres in 23 countries. We included patients with cancer aged 18 years or older, who had not received moderately or highly emetogenic chemotherapy before, with a Karnofsky performance score of 60 or higher, and a predicted life expectancy of 4 months or longer. We used an interactive web-based randomisation system to randomly allocate patients to receive either oral rolapitant (one 180 mg dose; rolapitant group) or a placebo that was identical in appearance (active control group) 1-2 h before administration of moderately emetogenic chemotherapy. Patients were stratified by sex. All patients also received granisetron (2 mg orally) and dexamethasone (20 mg orally) on day 1 (except for patients receiving taxanes as part of moderately emetogenic chemotherapy, who received dexamethasone according to the package insert) and granisetron (2 mg orally) on days 2-3. Every cycle was a minimum of 14 days. In up to five subsequent cycles, patients received the same study drug they were assigned in cycle 1, unless they chose to leave the study or were removed at the treating clinician's discretion. Efficacy analysis was done in the modified intention-to-treat population (comprising all patients who received at least one dose of study drug at a study site compliant with Good Clinical Practice [GCP]). The primary endpoint was the proportion of patients achieving a complete response (defined as no emesis or use of rescue medication) in the delayed phase (>24-120 h after initiation of chemotherapy) in cycle 1. This study is registered with ClinicalTrials.gov, number NCT01500226. The study has been completed. FINDINGS: Between March 5, 2012, and Sept 6, 2013, 1369 patients were randomised to receive either rolapitant (n=684) or active control (n=685). 666 patients in each group received at least one dose of study drug at a GCP-compliant site and were included in the modified intention-to-treat population. A significantly greater proportion of patients receiving rolapitant had complete responses in the delayed phase than did those receiving active control (475 [71%] vs 410 [62%]; odds ratio 1.6, 95% CI 1.2-2.0; p=0.0002). The incidence of adverse events was similar in the rolapitant and control groups, with the most frequently reported treatment-related treatment-emergent adverse events being fatigue, constipation, and headache. For cycle 1, the most common grade 3-4 adverse event in the rolapitant versus active control groups was neutropenia (32 [5%] vs 23 [3%] patients). No serious adverse event was treatment related, and no treatment-related treatment-emergent adverse event resulted in death. INTERPRETATION: Rolapitant in combination with a 5-HT3 receptor antagonist and dexamethasone is well tolerated and shows superiority over active control for the prevention of chemotherapy-induced nausea and vomiting during the 5-day (0 120 h) at-risk period after administration of moderately emetogenic chemotherapy or regimens containing an anthracycline and cyclophosphamide. FUNDING: TESARO, Inc. PMID- 26272769 TI - Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of cisplatin-based highly emetogenic chemotherapy in patients with cancer: two randomised, active-controlled, double blind, phase 3 trials. AB - BACKGROUND: Highly emetogenic chemotherapy induces emesis in almost all patients in the absence of prophylaxis. Guidelines recommend use of a neurokinin-1 (NK-1) receptor antagonist in conjunction with a 5-HT3 receptor antagonist and corticosteroid in patients receiving highly emetogenic chemotherapy. We aimed to assess rolapitant, an NK-1 receptor antagonist, for prevention of chemotherapy induced nausea and vomiting in patients with cancer after administration of cisplatin-based highly emetogenic chemotherapy. METHODS: We conducted two global, randomised, double-blind, active-controlled, phase 3 trials (HEC-1 and HEC-2) at 155 cancer centres (76 in HEC-1 and 79 in HEC-2) in 26 countries (17 in HEC-1 and 14 in HEC-2). We enrolled patients with cancer aged 18 years or older, who had not previously been treated with cisplatin, with a Karnofsky performance score of 60 or higher, and a predicted life expectancy of 4 months or longer. We used an interactive web-based randomisation system to randomly assign patients to treatment. Patients were stratified by sex and randomly allocated to either oral rolapitant (180 mg dose; rolapitant group) or a placebo that was identical in appearance (active control group) about 1-2 h before administration of highly emetogenic chemotherapy. All patients received granisetron (10 MUg/kg intravenously) and dexamethasone (20 mg orally) on day 1, and dexamethasone (8 mg orally) twice daily on days 2-4. Every cycle was a minimum of 14 days. In up to five subsequent cycles, patients were allowed to receive the same study drug they were assigned in cycle 1, unless removed at the clinician's discretion. Patients could also choose to leave the study at any point. Efficacy analysis was done in the modified intention-to-treat population (comprising all patients who received at least one dose of study drug at a cancer centre compliant with Good Clinical Practice [GCP]). The primary endpoint was the proportion of patients achieving a complete response (no emesis or use of rescue medication) in the delayed phase (>24-120 h after initiation of chemotherapy) in cycle 1. These studies are registered with ClinicalTrials.gov, numbers NCT01499849 and NCT01500213. Both studies have been completed. FINDINGS: Between Feb 21, 2012, and March 12, 2014, 532 patients in HEC-1 and 555 patients in HEC-2 were randomly assigned to treatment. 526 patients in HEC-1 (264 rolapitant and 262 active control) and 544 in HEC-2 (271 rolapitant and 273 active control) received at least one dose of study drug at a GCP-compliant site and were included in the modified intention-to treat population. A significantly greater proportion of patients in the rolapitant group had complete responses in the delayed phase than did patients in the active control group (HEC-1: 192 [73%] vs 153 [58%]; odds ratio 1.9, 95% CI 1.3-2.7; p=0.0006; HEC-2: 190 [70%] vs 169 [62%]; 1.4, 1.0-2.1; p=0.0426; pooled studies: 382 [71%] vs 322 [60%]; 1.6, 1.3-2.1; p=0.0001). The incidence of adverse events was similar across treatment groups. The most commonly reported treatment-related treatment-emergent adverse events in the rolapitant versus active control groups were headache (three [<1%] vs two [<1%]), hiccups (three [<1%] vs four [<1%]), constipation (two [<1%] vs three [<1%]), and dyspepsia (two [<1%] vs three [<1%]). For cycle 1, the most common grade 3-5 adverse events in patients allocated rolapitant versus active control were neutropenia (HEC-1: nine [3%] vs 14 [5%]; HEC-2: 16 [6%] vs 14 [5%]), anaemia (HEC-1: one [<1%] vs one [<1%]; HEC-2: seven [3%] vs two [<1%]), and leucopenia (HEC-1: six [2%] vs two [<1%]; HEC-2: two [<1%] vs two [<1%]). No serious treatment-emergent adverse events were treatment related, and no treatment-related treatment-emergent adverse events resulted in death. INTERPRETATION: Rolapitant in combination with a 5-HT3 receptor antagonist and dexamethasone is well-tolerated and shows superiority over active control for the prevention of chemotherapy-induced nausea and vomiting during the at-risk period (120 h) after administration of highly emetogenic cisplatin-based chemotherapy. FUNDING: TESARO, Inc. PMID- 26272771 TI - Bevacizumab: no comeback in early breast cancer? PMID- 26272772 TI - Role of rolapitant in chemotherapy-induced emesis. PMID- 26272770 TI - Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial. AB - BACKGROUND: NSABP B-40 was a 3 * 2 factorial trial testing whether adding capecitabine or gemcitabine to docetaxel followed by doxorubicin plus cyclophosphamide neoadjuvant chemotherapy would improve outcomes in women with operable, HER2-negative breast cancer and whether adding neoadjuvant plus adjuvant bevacizumab to neoadjuvant chemotherapy regimens would also improve outcomes. As reported previously, addition of neoadjuvant bevacizumab increased the proportion of patients achieving a pathological complete response, which was the primary endpoint. We present secondary patient outcomes, including disease free survival, a specified endpoint by protocol, and data for distant recurrence free interval, and overall survival, which were not prespecified endpoints but were collected prospectively. METHODS: In this randomised controlled trial (NSABP B-40), we enrolled women aged 18 years or older, with operable, HER2-non amplified invasive adenocarcinoma of the breast, 2 cm or greater in diameter by palpation, clinical stage T1c-3, cN0, cN1, or cN2a, without metastatic disease and diagnosed by core needle biopsy. Patients received one of three docetaxel based neoadjuvant regimens for four cycles: docetaxel alone (100 mg/m(2)) with addition of capecitabine (825 mg/m(2) oral twice daily days 1-14, 75 mg/m(2) docetaxel) or with addition of gemcitabine (1000 mg/m(2) days 1 and 8 intravenously, 75 mg/m(2) docetaxel), all followed by neoadjuvant doxorubicin and cyclophosphamide (60 mg/m(2) and 600 mg/m(2) intravenously) every 3 weeks for four cycles. Those randomly assigned to bevacizumab groups were to receive bevacizumab (15 mg/kg, every 3 weeks for six cycles) with neoadjuvant chemotherapy and postoperatively for ten doses. Randomisation was done (1:1:1:1:1:1) via a biased-coin minimisation procedure to balance the characteristics with respect to clinical nodal status, clinical tumour size, hormone receptor status, and age. Intent-to-treat analyses were done for disease free survival and overall survival. This study is registered with ClinicalTrials.gov, number NCT00408408. FINDINGS: Between Jan 5, 2007, and June 30, 2010, 1206 patients were enrolled in the study. Follow-up data were collected from Oct 31, 2007 to March 27, 2014, and were available for overall survival in 1186 patients, disease-free survival in 1184, and distant recurrence-free interval in 1181. Neither capecitabine nor gemcitabine increased disease-free survival or overall survival. Median follow-up was 4.7 years (IQR 4.0-5.2). The addition of bevacizumab significantly increased overall survival (hazard ratio 0.65 [95% CI 0.49-0.88]; p=0.004) but did not significantly increase disease-free survival (0.80 [0.63-1.01]; p=0.06). Four deaths occurred on treatment due to vascular disorder (docetaxel plus capecitabine followed by doxorubicin plus cyclophosphamide group), sudden death (docetaxel plus capecitabine followed by doxorubicin plus cyclophosphamide group), infective endocarditis (docetaxel plus bevacizumab followed by doxorubicin plus cyclophosphamide and bevacizumab group), and visceral arterial ischaemia (docetaxel followed by doxorubicin plus cyclophosphamide group). The most common grade 3-4 adverse events in the bevacizumab group were neutropenia (grade 3, 99 [17%]; grade 4, 37 [6%]), hand foot syndrome (grade 3, 63 [11%]), and hypertension (grade 3, 60 [10%]; grade 4, two [<1%]) and in the non-bevacizumab group were neutropenia (grade 3, 98 [16%]; grade 4, 36 [6%]), fatigue (grade 3, 53 [9%]), and hand-foot syndrome (grade 3, 43 [7%]). INTERPRETATION: The addition of gemcitabine or capecitabine to neoadjuvant docetaxel plus doxorubicin plus cyclophosphamide does not seem to provide any benefit to patients with operable breast cancer, and should not change clinical practice in the short term. The improved overall survival with bevacizumab contradicts the findings of other studies of bevacizumab in breast cancer and may indicate the need for additional investigation of this agent. FUNDING: National Institutes of Health, Genentech, Roche Laboratories, Lilly Research Laboratories, and Precision Therapeutics. PMID- 26272773 TI - Docemur Docemus: Peer-Assisted Learning Improves the Knowledge Gain of Tutors in the Highest Quartile of Achievement but Not Those in the Lowest Quartile. AB - OBJECTIVES: Peer-assisted learning (PAL) is a form of collaborative learning where members of a peer group act as teachers for each other. A reciprocal PAL program was designed to investigate whether there were differential gains in knowledge acquisition among tutors compared with tutees. DESIGN: Bayesian statistical analysis was used to quantitatively assess the effect of tutor status on performance in a knowledge-based examination. Subgroup analysis according to student achievement and question difficulty was performed. PARTICIPANTS AND SETTING: Final year undergraduate medical students in a 5-year degree program (n = 126). RESULTS: The overall probability of getting a correct answer on the knowledge examination was 49.7%. For questions on topics where a student had acted as a tutor this improved to 57.3%. However, students who performed in the upper quartile had a greater percentage gain in the probability of a correct answer in topics that they had taught vs students who performed in the lowest quartile. CONCLUSIONS: There was demonstrable overall knowledge gain associated with acting as a tutor in a PAL program but the greatest gain occurred in students of highest academic ability. PMID- 26272774 TI - A Diagnostic Pitfall: Salmonella Splenic Infarction in Hereditary Spherocytosis. PMID- 26272775 TI - Reversible parkinsonism with lentiform fork sign as an initial and dominant manifestation of uremic encephalopathy. PMID- 26272776 TI - Anxiety and depression in Parkinson's disease patients in Saudi Arabia Global neurology. PMID- 26272777 TI - Antibacterial and conductive injectable hydrogels based on quaternized chitosan graft-polyaniline/oxidized dextran for tissue engineering. AB - Biomaterials with injectability, conductivity and antibacterial effect simultaneously have been rarely reported. Herein, we developed a new series of in situ forming antibacterial conductive degradable hydrogels using quaternized chitosan (QCS) grafted polyaniline with oxidized dextran as crosslinker. The chemical structures, morphologies, electrochemical property, conductivity, swelling ratio, rheological property, in vitro biodegradation and gelation time of hydrogels were characterized. Injectability was verified by in vivo subcutaneous injection on a Sprague Dawley rat. The antibacterial activity of the hydrogels was firstly evaluated employing antibacterial assay using Escherichia coli and Staphylococcus aureus in vitro. The hydrogels containing polyaniline showed enhanced antibacterial activity compared to QCS hydrogel, especially for hydrogels with 3 wt% polyaniline showing 95 kill% and 90kill% for E. coli and S. aureus, respectively. Compared with QCS hydrogel, the hydrogels with 3 wt% polyaniline still showed enhanced antibacterial activity for E. coli in vivo. The adipose-derived mesenchymal stem cells (ADMSCs) were used to evaluate the cytotoxicity of the hydrogels and hydrogels with polyaniline showed better cytocompatibility than QCS hydrogel. The electroactive hydrogels could significantly enhance the proliferation of C2C12 myoblasts compared to QCS hydrogel. This work opens the way to fabricate in situ forming antibacterial and electroactive degradable hydrogels as a new class of bioactive scaffolds for tissue regeneration applications. PMID- 26272778 TI - Sensitivity and Specificity of the Phallometric Test for Hebephilia. AB - INTRODUCTION: The phallometric test has been examined most widely in the literature with regard to its ability to detect pedophilia; however, it has become of increasing interest to clinicians and researchers to ascertain to what extent the test accurately detects hebephilia: Whereas pedophilia refers to an adult's sexual interest in prepubescent children (age 10 or younger, on average), hebephilia refers to an adult's sexual interest in pubescent children (ages 11 14, on average). AIM: The aim of this study was to estimate the accuracy of volumetric phallometry in distinguishing pedophilic men and hebephilic men from men who are teleiophilic (primarily sexually interested in adults, age 17 or older). METHODS: A retrospective chart review was conducted on the cumulate database of a large phallometric laboratory and clinic to identify a group of 239 men who committed sexual offenses against extrafamilial adults age 17 or older and a group of 996 men who committed sexual offenses against extrafamilial children age 14 or younger, all of whom professed a greater sexual interest in adults over children. MAIN OUTCOME MEASURES: The sensitivity and specificity of the phallometric test is calculated for its accuracy in distinguishing sexual preferences for children spanning various age ranges. RESULTS: Receiver operator characteristic curves were highly significant for each classification decision: Using its previously established cut-point of +0.25 standard deviation (SD) units, the phallometric test detected hebephilia with a sensitivity and specificity of 70.0% and 90.7%, detected pedophilia with 46.9% and 100%, and detected pedohebephilia with 75.3% and 90.7%. At a new cut-point of +0.0 SD units, the sensitivity and specificity of the test for pedophilia was 71.9% and 95.3%. CONCLUSIONS: Volumetric phallometry significantly distinguishes teleiophilic sex offenders from each of pedophilic, hebephilic, and pedohebephilic sex offenders and can serve as a reliable diagnostic test of sexual age preference among men who deny sexual interest in children. PMID- 26272779 TI - Childhood abuse victimization, stress-related eating, and weight status in young women. AB - PURPOSE: Abuse in childhood predicts stress-related overeating and excess weight gain in young women. We investigated whether two stress-related overeating behaviors--binge eating and coping-motivated eating--explain childhood abuse associations with weight status in young women. METHODS: Analyses included 4377 women participating in the Growing Up Today Study, a longitudinal cohort of youth enrolled at age 9 to 14 years. We used marginal structural models to estimate the effects of abuse before age 11 years on weight status at age 22 to 29 years with and without adjustment for binge eating and coping-motivated eating. RESULTS: Women with severe physical, sexual, and emotional abuse had early adult body mass indexes (BMIs) that were 0.74 kg/m(2) (95% confidence interval [CI]: 0.15-1.33), 0.69 (95% CI: -0.46 to 1.83), and 0.85 (95% CI: 0.24-1.45) kg/m(2) higher, respectively, than those without abuse. Adjustment for coping-motivated eating attenuated the excess BMI associated with severe physical abuse, but no other important attenuations were found. CONCLUSIONS: Physical, sexual, and emotional abuse before age 11 years were associated with higher early adult weight status, although the sexual abuse estimate was not statistically significant. Evidence for a role of stress-related eating in abuse--BMI associations was limited and inconsistent across abuse types. PMID- 26272780 TI - The prevalence and secular trends of abdominal obesity among Chinese adults, 1993 2011. PMID- 26272782 TI - One-Year Efficacy Testing of Enabling Mothers to Prevent Pediatric Obesity Through Web-Based Education and Reciprocal Determinism (EMPOWER) Randomized Control Trial. AB - BACKGROUND: The purpose of this study was to evaluate the efficacy of the Enabling Mothers to Prevent Pediatric Obesity through Web-Based Education and Reciprocal Determinism (EMPOWER) intervention at 1-year, postintervention follow up. METHOD: A mixed between-within subjects design was used to evaluate the trial. Independent variables included a two-level, group assignment: EMPOWER (experimental intervention) based on social cognitive theory (SCT) as well as a knowledge-based intervention Healthy Lifestyles (active control intervention). Dependent variables were evaluated across four levels of time: baseline (Week 0), posttest (Week 4), 1-month follow-up (Week 8), and 1-year follow-up (Week 60). Dependent variables included five maternal-facilitated SCT constructs (environment, emotional coping, expectations, self-control, and self-efficacy) as well as four child behaviors (minutes of child physical activity, cups of fruits and vegetables consumed, 8-ounce glasses of sugar-sweetened beverages consumed, and minutes of screen time). Null hypotheses implied no significant group-by-time interactions for the dependent variables under investigation. RESULTS: A significant group-by-time interaction for child fruit and vegetable consumption was found in the experimental group (p = .012) relative to the control group. At 1 year, results suggested an overall increase of 1.847 cups of fruits and vegetables (95% confidence interval = 1.207-2.498) in the experimental group (p < .001). Analysis suggested changes in the maternal-facilitated home environment accounted for 13.3% of the variance in the change in child fruit and vegetable consumption. Improvements in child physical activity, sugar-free beverage intake, and screen time first detected at 1-month follow-up in both groups were no longer significant at 1-year follow-up. CONCLUSIONS: An online family-and-home-based intervention was efficacious for improving child fruit and vegetable consumption. Follow-up booster sessions may assist in maintaining treatment effects. PMID- 26272781 TI - High-intensity sweetener consumption and gut microbiome content and predicted gene function in a cross-sectional study of adults in the United States. AB - PURPOSE: To evaluate gut microbiome in relation to recent high-intensity sweetener consumption in healthy adults. METHODS: Thirty-one adults completed a four-day food record and provided a fecal sample on the fifth day. Bacterial community in the samples was analyzed using multitag pyrosequencing. Across consumers and nonconsumers of aspartame and acesulfame-K, bacterial abundance was compared using nonparametric statistics, and bacterial diversity was compared using UniFrac analysis. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict mean relative abundance of gene function. RESULTS: There were seven aspartame consumers and seven acesulfame-K consumers. Three individuals overlapped groups, consuming both sweeteners. There were no differences in median bacterial abundance (class or order) across consumers and nonconsumers of either sweetener. Overall bacterial diversity was different across nonconsumers and consumers of aspartame (P < .01) and acesulfame-K (P = .03). Mean predicted gene abundance did not differ across consumers and nonconsumers of aspartame or acesulfame-K. CONCLUSIONS: Bacterial abundance profiles and predicted gene function were not associated with recent dietary high-intensity sweetener consumption. However, bacterial diversity differed across consumers and nonconsumers. Given the increasing consumption of sweeteners and the role that the microbiome may have in chronic disease outcomes, work in further studies is warranted. PMID- 26272784 TI - Stress, Health Risk Behaviors, and Weight Status Among Community College Students. AB - The objective of this study was to describe the relationship between stress, weight-related health risk behaviors (e.g., eating behaviors, physical activity, sedentary behavior, sleep, cigarette smoking, and binge drinking), and weight status using cross-sectional data on 2-year community college students enrolled in a randomized controlled weight gain prevention trial. Modified Poisson regression and linear regression were used to examine crude and adjusted cross sectional associations. Higher stress was associated with higher prevalence of overweight/obesity (crude prevalence ratio [PR] = 1.05; 95% confidence interval [CI: 1.01, 1.09]), though the relationship was no longer statistically significant after controlling for a wide range of weight-related health risk behaviors (adjusted PR = 1.04; 95% CI [1.00, 1.08]). Stress levels were significantly associated with meal skipping and being a current smoker. Future research should investigate the mechanisms through which stress is related to obesity risk and examine the causes of stress among this understudied population to inform the design of appropriate interventions. PMID- 26272783 TI - Postpartum Teens' Perception of the Food Environments at Home and School. AB - BACKGROUND: An environment that supports healthy eating is one factor to prevent obesity. However, little is known about postpartum teen's perceptions of their home and school environments and how this relates to dietary behaviors. PURPOSE: This study explores the relationship between home and school environments and dietary behaviors for postpartum teens. DESIGN: Conducted cross-sectionally during 2007-2009 across 27 states and included 889 postpartum teens enrolled in Parents as Teachers Teen Program. Data included measures of sociodemographics and perceptions of school and home food environments. A 7-day recall of snack and beverage frequency assessed dietary behaviors. Logistic regression explored associations between baseline environment measures and dietary behaviors at baseline and postintervention (approximately 5 months after baseline) for the control group. RESULTS: Respondents reported greater access and selection (i.e., variety of choices) of healthy foods and beverages at home than school. At baseline, fruit and vegetable intake was associated with home selection (1.9, 95% confidence interval [CI: 1.3, 2.9]) and availability (1.8, 95% CI [1.3, 2.6]), sweet snack consumption was associated with selection (1.5, 95% CI [1.0, 2.1]), and total snack consumption and sugar-sweetened beverage intake were associated with selection (snack: 2.1, 95% CI [1.5, 3.0]; beverage: 1.7, 95% CI [1.2, 2.4]) and availability (snack: 2.1, 95% CI [1.4, 3.1]; beverage: 1.5, 95% CI [1.0, 2.3]). Water intake at baseline and at the postintervention for control group teens was associated with selection (1.6, 95% CI [1.1, 2.2]). No significant associations were identified between the school environment and dietary behaviors. CONCLUSIONS: Interventions should target improvements in the home environment for high-risk, postpartum teens. PMID- 26272785 TI - Hip Hop HEALS: Pilot Study of a Culturally Targeted Calorie Label Intervention to Improve Food Purchases of Children. AB - OBJECTIVES: We explored the effect of a culturally targeted calorie label intervention on food purchasing behavior of elementary school students. METHOD: We used a quasi-experimental design with two intervention schools and one control school to assess food purchases of third through fifth graders at standardized school food sales before and after the intervention (immediate and delayed) in schools. The intervention comprised three 1-hour assembly-style hip-hop-themed multimedia classes. RESULTS: A mean total of 225 children participated in two baseline preintervention sales with and without calorie labels; 149 children participated in immediate postintervention food sales, while 133 children participated in the delayed sales. No significant change in purchased calories was observed in response to labels alone before the intervention. However, a mean decline in purchased calories of 20% (p < .01) and unhealthy foods (p < .01) was seen in immediately following the intervention compared to baseline purchases, and this persisted without significant decay after 7 days and 12 days. CONCLUSION: A 3-hour culturally targeted calorie label intervention may improve food-purchasing behavior of children. PMID- 26272786 TI - The HIV Risk Profiles of Latino Sexual Minorities and Transgender Persons Who Use Websites or Apps Designed for Social and Sexual Networking. AB - The use of websites and GPS-based mobile applications ("apps") designed for social and sexual networking has been associated with increased HIV risk; however, little is known about Latino sexual minorities' and transgender persons' use of these websites and apps and the risk profiles of those who use them compared with those who do not. Data from 167 participants who completed the baseline survey of a community-level HIV prevention intervention, which harnesses the social networks of Latino sexual minorities and transgender persons, were analyzed. One quarter of participants (28.74%, n = 48) reported using websites or apps designed for social and sexual networking, and 119 (71.26%) reported not using websites or apps designed for social and sexual networking. Those who used websites or apps were younger and reported more male sex partners, a sexually transmitted disease diagnosis, and illicit drug use other than marijuana. HIV prevention interventions for those who use websites or apps should consider addressing these risks for HIV. PMID- 26272787 TI - Marfan syndrome patient experiences as ascertained through postings on social media sites. AB - Marfan syndrome (MS) is a connective tissue disorder that affects thousands of adolescents [Population Reference Bureau, 2013]. Some adolescent patients with MS may use social media to express their experiences and emotions, but little is known about what patients choose to share online. To investigate social media content related to Marfan syndrome we used search terms "Marfan syndrome" and "Marfans" on six different social media sites. The top five recent and popular posts for each site were collected and coded weekly for five weeks. Posts were excluded if they were reshared content or not in English. A codebook was developed using an iterative process to categorize posts and comments. Out of 300 posts collected 147 posts (49.0%) were included for evaluation. Categories of displayed content included personal pictures, memes and pictures featuring symptoms of MS (41.5%) and personal MS experiences (27.1% of posts). One quarter of the posts specifically mentioned a positive experience or how thankful the profile owner was for their life. A unique category of posts (13.7%) referenced Austin Carlile, a celebrity singer with MS, as a role model. Physicians and healthcare providers may consider using social media to understand common MS concerns and to place future health education materials. PMID- 26272789 TI - Macrocyclic weakly coordinating anions. AB - Herein, the concept of macrocyclic weakly coordinating anions (M-WCAs) is introduced. Synthetic methodologies are described how to access M-WCAs by thermodynamically controlled self-assembly in high yields, in particular through condensation and alkyne metathesis reactions. The anticipated properties and applications of M-WCAs in solid state and in solution are discussed, specifically for gas storage and separation, homogeneous and heterogeneous catalysis, and as liquid and solid electrolytes. PMID- 26272788 TI - Thermus anatoliensis sp. nov., a thermophilic bacterium from geothermal waters of Buharkent, Turkey. AB - A Gram-stain-negative, lack of motility, catalase- and oxidase- positive bacterium (strain MT1(T)) was isolated from Buharkent hot spring in Aydin, Turkey. Its taxonomy was investigated using a polyphasic approach. The strain was able to grow at 45-80 degrees C, pH 5.5-10.5 and with a NaCI tolerance up to 2.0% (w/v). Strain MT1(T) was able to utilize d-mannitol and l-arabinose, not able to utilize d-cellobiose as sole carbon source. 16S rRNA gene sequence analysis revealed that the strain belonged to the genus Thermus; strain MT1(T) detected low-level similarities of 16S rRNA gene sequences (below 97%) compared with all other species in this genus. The predominant fatty acids of strain MT1(T) were iso-C(15:0) (43.0%) and iso-C(17:0) (27.4%). Polar lipid analysis revealed a major phospholipid, one major glycolipid, one major aminophospholipid, two minor aminolipids, one minor phospholipid, and several minor glycolipids. The major isoprenoid quinone was MK-8. The DNA G+C content of MT1(T) was 69.6 mol%. On the basis of a taxonomic study using a polyphasic approach, strain MT1(T) is considered to represent a novel species of the genus Thermus, for which the name Thermus anatoliensis sp. nov. is proposed. The type strain is MT1(T) (=NCCB 100425(T) =LMG 26880(T)). PMID- 26272790 TI - An evaluation of the difficulties and attitudes mental health professionals experience with people with personality disorders. AB - INTRODUCTION: Working with people with a personality disorder (PD) can arouse strong feelings, and cause difficulties as well as different attitudes among mental health workers (MHWs). While attitudes towards people with PD and the difficulties experienced by MHWs have been previously investigated, the reciprocal relationship between the two has not been thoroughly investigated. AIM/QUESTION: This study aims to investigate (1) affective reactions of MHWs to people with personality disorders, (2) the difficulties that MHWs experience while working with these patients, (3) their attitudes towards these patients, and (4) the interaction between these variables. METHOD: The data for this study were collected through a Personal Information Questionnaire, the Difficulty of Working with Personality Disorders Scale and the Attitudes towards Patients with Personality Disorders Scale from 332 MHWs from several mental health clinics in Turkey, all of whom were experienced in working with people with PD. RESULTS: The results indicate that the participants described 'difficulty in forming a relationship, understanding the client, and establishing cooperation' among the primary reasons of difficulties. This study also shows that there is a strong relationship between MHWs' feelings of boredom/discontent, guilt/pity and a tendency to display positive behaviours/an inability of establishing borders against people with PD. DISCUSSION: The findings of this study imply that the level of education, expertise, psychotherapy treatment and clinical supervision of MHWs all affect perceived difficulties and attitudes towards people with PD. It is also noted that among nurses, a higher level of education results in reduced experience of difficulties while working with patients with PD. IMPLICATION FOR PRACTICE: The results foreground the need for specific skills to be developed in MHWs through theoretical training, case-focused supervision and receiving personal psychotherapy for MHWs. PMID- 26272791 TI - CONSORT extension for reporting N-of-1 trials (CENT) 2015: explanation and elaboration. AB - N-of-1 trials are a useful tool for clinicians who want to determine the effectiveness of a treatment in a particular individual. The reporting of N-of-1 trials has been variable and incomplete, hindering their usefulness in clinical decision making and by future researchers. This document presents the CONSORT (Consolidated Standards of Reporting Trials) extension for N-of-1 trials (CENT 2015). CENT 2015 extends the CONSORT 2010 guidance to facilitate the preparation and appraisal of reports of an individual N-of-1 trial or a series of prospectively planned, multiple, crossover N-of-1 trials. CENT 2015 elaborates on 14 items of the CONSORT 2010 checklist, totalling 25 checklist items (44 sub items), and recommends diagrams to help authors document the progress of one participant through a trial or more than one participant through a trial or series of trials, as applicable. Examples of good reporting and evidence based rationale for CENT 2015 checklist items are provided. PMID- 26272793 TI - A framework to assess the value of application of formal criteria to check clinical relevance in RCTs as part of a benefit assessment strategy. AB - Recently, the topic of assessing clinical relevance on top of statistical significance in the analysis of randomized control trials (RCTs) has got increasing attention, in particular as part of benefit assessments. Several formal criteria to serve this purpose have been published. In this paper, we present a framework to assess the value of the application of such criteria. We propose to quantify the need for the assessment of clinical relevance by the actual risk of having accepted a benefit for a treatment with an irrelevant effect in a successful RCT. We then study how this risk can be controlled by two popular criteria based on comparing the effect estimate or the lower bound of the confidence interval with a given threshold. We further propose to quantify the impact of using formal criteria by considering the expected costs when specifying error-specific costs for each of the three possible types of errors: A benefit may be accepted for a treatment, which is actually inferior, or which is not inferior, but only implies an irrelevant improvement, or a benefit may be rejected for a treatment implying a relevant improvement. This way we can demonstrate that the impact depends on parameters which are typically not explicitly defined in the frame of benefit assessments. Depending on the values of these parameters, formal checks of clinical relevance may imply better decisions on average, but they may also imply more harm than good on average. PMID- 26272792 TI - CONSORT extension for reporting N-of-1 trials (CENT) 2015 Statement. AB - N-of-1 trials provide a mechanism for making evidence-based treatment decisions for an individual patient. They use key methodological elements of group clinical trials to evaluate treatment effectiveness in a single patient, for situations that cannot always accommodate large-scale trials: rare diseases, comorbid conditions, or in patients using concurrent therapies. Improvement in the reporting and clarity of methods and findings in N-of-1 trials is essential for reader to gauge the validity of trials and to replicate successful findings. A Consolidated Standards of Reporting Trials (CONSORT) extension for N-of-1 trials (CENT 2015) provides guidance on the reporting of individual and series of N-of-1 trials. CENT provides additional guidance for 14 of the 25 items of the CONSORT 2010 checklist, recommends a diagram for depicting an individual N-of-1 trial, and modifies the CONSORT flow diagram to address the flow of a series of N-of-1 trials. The rationale, development process, and CENT 2015 checklist and diagrams are reported in this document. PMID- 26272795 TI - Hand Therapy Modalities for Proximal Interphalangeal Joint Stiffness. PMID- 26272796 TI - The Hand and Wrist in Juvenile Rheumatoid Arthritis. PMID- 26272797 TI - What does the closure of context-sensitive constraints mean for determinism, autonomy, self-determination, and agency? AB - The role of context-sensitive constraints - first as enablers of complexification and subsequently as regulators that maintain the integrity of self-organized, coherent wholes - has only recently begun to be examined. Conceptualizing such organizational constraints in terms of the operations of far from equilibrium, nonlinear dynamic processes rekindles old metaphysical discussions concerning primary and secondary relations, emergence, causality, and the logic of explanation. In particular, far-from-equilibrium processes allow us to rethink how parts-to-whole and whole-to-parts - so-called "mereological"- relationships are constituted. A renewed understanding of recursive feedback and the role context-dependence plays in generating the boundary conditions and the internal organization of complex adaptive systems in turn allows us to redescribe formal and final cause in such a way as to provide a meaningful sense of heretofore seemingly intractable philosophical problems such as autonomy, self determination, and agency. PMID- 26272794 TI - MIEN1, a novel interactor of Annexin A2, promotes tumor cell migration by enhancing AnxA2 cell surface expression. AB - BACKGROUND: Migration and invasion enhancer 1 (MIEN1) is a novel gene found to be abundantly expressed in breast tumor tissues and functions as a critical regulator of tumor cell migration and invasion to promote systemic metastases. Previous studies have identified post-translational modifications by isoprenylation at the C-terminal tail of MIEN1 to favor its translocation to the inner leaflet of plasma membrane and its function as a membrane-bound adapter molecule. However, the exact molecular events at the membrane interface activating the MIEN1-driven tumor cell motility are vaguely understood. METHODS: MIEN1 was first studied using in-silico analysis on available RNA sequencing data of human breast tissues and its expression was ascertained in breast cells. We performed several assays including co-immunoprecipitation, wound healing, western blotting and immunofluorescence to decipher the molecular events involved in MIEN1-mediated tumor cell migration. RESULTS: Clinically, MIEN1 is predominantly overexpressed in Her-2 and luminal B subtypes of breast tumors, and its increased expression correlates with poor disease free survival. Molecular studies identified a phosphorylation-dependent activation signal in the immunoreceptor tyrosine based activation motif (ITAM) of MIEN1 and the phosphorylation-deficient MIEN1-mutants (Y39F/50 F) to regulate filopodia generation, migration and invasion. We found that ITAM-phosphorylation of MIEN1 is significantly impaired in isoprenylation-deficient MIEN1 mutants indicating that prenylation of MIEN1 and membrane association is required for cross-phosphorylation of tyrosine residues. Furthermore, we identified MIEN1 as a novel interactor of Annexin A2 (AnxA2), a Ca(2+) -dependent phospholipid binding protein, which serves as an extracellular proteolytic center regulating plasmin generation. Fluorescence resonance energy transfer (FRET) confirmed that MIEN1 physically interacts with AnxA2 and functional studies revealed that they mutually cooperate to accentuate tumor cell motility. Interestingly, our study identified that ectopic overexpression of MIEN1 significantly enhances Tyr23-phosphorylation on AnxA2, thereby stimulating cell surface translocation of AnxA2 and catalyzing the activation of its proteolytic activity. CONCLUSION: Our data show that the presence and interaction of both MIEN1 and AnxA2 in breast tumors are crucial drivers of cell motility. Our study has now deciphered a novel regulatory network governing the vicious process of breast tumor cell invasion-metastasis, and findings suggest MIEN1-AnxA2 as prospective targets to counter the deadly disease. PMID- 26272798 TI - Naturalizing phenomenology - A philosophical imperative. AB - Phenomenology since Husserl has always had a problematic relationship with empirical science. In its early articulations, there was Husserl's rejection of 'the scientific attitude', Merleau-Ponty's distancing of the scientifically objectified self, and Heidegger's critique of modern science. These suggest an antipathy to science and to its methods of explaining the natural world. Recent developments in neuroscience have opened new opportunities for an engagement between phenomenology and cognitive science and through this, a re-thinking of science and its hidden assumptions more generally. This is so partly because of the shortcomings of conventional mechanistically-conceived science in dealing with complex and dynamic phenomena such as climate change, brain plasticity, the behaviour of collectives, the dynamics of various microbiological processes, etc. But it is also due to recent phenomenological scholarship focussed on the 'embodied' phenomenology of Husserl's Ideen II and Merleau Ponty's later ontology of nature which have helped to extend the insights of phenomenology beyond the narrowly 'human' to an understanding of nature (which includes the human) more generally. Thus re-contextualised, phenomenology is well placed to examine some of the assumptions that give rise to the reductionism and associated scientism which has characterised conventional science in its approach to the study of natural processes. In light of this, it might be suggested that the 'anti science' of early articulations of phenomenology is more a hostility to the underlying assumptions of science as conventionally understood than to science itself - that it is scientism rather than science that is targeted. In this paper, I aim to show how a phenomenological naturalism might be seen as a necessary step towards the development of a non-reductionist and non-scientistic approach to scientific inquiry. A key to this is a reconceptualization of nature as inclusive of meanings and of mind. It is a conception developed by Merleau Ponty, especially in his later ontology of nature, and one that is shared by American pragmatist philosopher of science, C.S. Peirce (1839-1914). For both philosophers, meaning must be understood in terms of an ontology which is relational rather than atomistic, and dynamic or processual rather than static and substance-based. For Merleau-Ponty this is an experientially-derived ontology; for Peirce it is a more conceptually-based one. In this paper, I explore this connection between these two philosophers in two stages. The first is by reference to Peirce's theory of signs or semiotics. More specifically, I look at the application of this theory to the study of biological processes as developed in Peirce-inspired biosemiotics. In the light of this, I suggest that Merleau-Ponty's account of intentional relations in nature might be articulated as semiotic relations, and can serve as a philosophical basis for a non-reductive biological science. I then turn to questions relating to the ontology of nature. I explore Merleau-Ponty's experientially-based "ontology of flesh" and Peirce's distinctive form of naturalism to show affinities at this ontological level. These affinities consist in commitments to a reality that includes possibility, meaning, temporality, and final causation - that is, an ontology which is far more inclusive than that of conventional positivistic science. Peirce's broader scientific metaphysics enables us to extend Merleau-Ponty's phenomenological naturalism beyond the biological to the physical sciences. Whilst Merleau-Ponty's ontology of nature provides the experiential basis necessary for a critique of scientism, Peirce establishes the relevance of that ontology for a re-conceived empirical science. PMID- 26272799 TI - Emotional sentience and the nature of phenomenal experience. AB - When phenomenal experience is examined through the lens of physics, several conundrums come to light including: Specificity of mind-body interactions, feelings of free will in a deterministic universe, and the relativity of subjective perception. The new biology of "emotion" can shed direct light upon these issues, via a broadened categorical definition that includes both affective feelings and their coupled (yet often subconscious) hedonic motivations. In this new view, evaluative (good/bad) feelings that trigger approach/avoid behaviors emerged with life itself, a crude stimulus-response information loop between organism and its environment, a semiotic signaling system embodying the first crude form of "mind". Emotion serves the ancient function of sensory-motor self regulation and affords organisms - at every level of complexity - an active, adaptive, role in evolution. A careful examination of the biophysics involved in emotional "self-regulatory" signaling, however, acknowledges constituents that are incompatible with classical physics. This requires a further investigation, proposed herein, of the fundamental nature of "the self" as the subjective observer central to the measurement process in quantum mechanics, and ultimately as an active, unified, self-awareness with a centrally creative role in "self organizing" processes and physical forces of the classical world. In this deeper investigation, a new phenomenological dualism is proposed: The flow of complex human experience is instantiated by both a classically embodied mind and a deeper form of quantum consciousness that is inherent in the universe itself, implying much deeper - more Whiteheadian - interpretations of the "self-regulatory" and "self-relevant" nature of emotional stimulus. A broad stroke, speculative, intuitive sketch of this new territory is then set forth, loosely mapped to several theoretical models of consciousness, potentially relevant mathematical devices and pertinent philosophical themes, in an attempt to acknowledge the myriad questions - and limitations - implicit in the quest to understand "sentience" in any ontologically pansentient universe. PMID- 26272800 TI - Re-live and learn - Interlocutor-induced elicitation of phenomenal experiences in learning offline. AB - Contemporary neuroscience studies propose that sensory-motor experiences in the form of 're-enactments' or 'simulations' are significant to the individual's development of concepts and language use. To a certain extent, such studies align with non-Cartesian perspectives on situated cognition. Since perceptual activity is reflected neurally, however, the neural perspective of experiences and re enactments allows us to distinguish between online and offline conditions within situated cognition, thereby addressing the extent to which direct experiences contribute to a particular learning episode. Whereas online situated cognition reflects the 'traditional' 4e's (minds as embodied, embedded, enacted, and extended) and focus is on cognitive processes confined to the individual, offline situated cognition introduces Others as significant contributors to cognitive processes in the individual. In this paper, I analyse how offline situated cognition entails a hitherto underdescribed but radical receptivity to the social world that works through language. Based on the unfolding of how we acquire the concepts of mental states as part of theory of mind, I establish that in the hands of interlocutors, words cultivate minds by first eliciting phenomenal sensations and then facilitating an association of these to experiences that originate with a different phenomenal content. Thus, I conclude both that phenomenal experiences online are central to conceptual learning offline through re-enactions and that Others are profoundly essential in forming cognising Selves. PMID- 26272801 TI - The importance of the proximal resection margin distance for proximal gastric adenocarcinoma: A multi-institutional study of the US Gastric Cancer Collaborative. AB - BACKGROUND: A 5 cm margin is advocated for distal gastric adenocarcinoma (GAC). The optimal proximal resection margin (PM) length for proximal GAC is not established. METHODS: Patients who underwent curative-intent resection for proximal GAC from 2000 to 2012 at 7 centers in the US Gastric Cancer Collaborative were included. PM length was sequentially dichotomized and analyzed at 0.5 cm increments (0.5-6.5 cm). Outcomes after negative margin (R0) and positive microscopic margin (R1) resections were compared. Primary endpoints were local recurrence (LR) and overall survival (OS). RESULTS: All patients (n = 162) had R0 distal margins. 151 (93.2%) had an R0-PM with mean length of 2.6 cm (median:1.7 cm; range:0.1-15 cm). A greater PM distance was not associated with LR or OS. An R1-PM was associated with higher N-stage (N3:73% vs. 26%; P = 0.007) and increased LR (HR6.1; P = 0.009) but not associated with decreased OS. On multivariate analysis, an R1-PM was also not independently associated with LR. CONCLUSIONS: For resection of proximal gastric adenocarcinoma, proximal margin length is not associated with local recurrence or overall survival. An R1 margin is associated with advanced N-stage but is not independently associated with recurrence or survival. When performing resection of proximal gastric adenocarcinoma, efforts to achieve a specific margin distance, especially if it necessitates an esophagectomy, should be abandoned. PMID- 26272802 TI - Isolated C-C joint tuberculosis - A diagnostic dilemma. AB - Painful lytic lesions of the foot raise a diagnostic dilemma for the foot surgeon. The localization of the lytic lesion in the mid foot is rare and isolated involvement of the calcaneo-cuboid (C-C) joint is even rarer. Early diagnosis is imperative in the mid foot to avoid rapid disease spread due to multiple venous interconnections. The diagnostic possibilities include infection, tumor (primary and metastasis), inflammatory arthritis, foreign body prick among others. The clues to rule out other differential diagnoses of lytic lesions can be history and examination, both clinical and radiographic but the gold standard for final diagnosis remains biopsy and histo-pathological examination. We describe two cases of lytic lesion around the calcaneo-cuboid joint and discuss the diagnostic dilemma. The lesions were diagnosed as tubercular in nature after histo-pathological examination of open biopsy. Both cases had complete resolution of lytic lesions and had fair functional outcome after completing the course of anti-tubercular therapy. Tuberculosis (TB) is making a worldwide resurgence due to the epidemic of HIV. In order to control this global epidemic of TB, it is important to know about all the possible presentations of the disease, including rare ones. Tuberculosis if diagnosed early in the disease course, when the pathology is localized, can result in good to fair results in the foot if adequately managed by anti-tubercular therapy. LEVEL OF EVIDENCE: V. PMID- 26272803 TI - Gastrointestinal symptoms among endometriosis patients--A case-cohort study. AB - BACKGROUND: Women with endometriosis often experience gastrointestinal symptoms. Gonadotropin-releasing hormone (GnRH) analogs are used to treat endometriosis; however, some patients develop gastrointestinal dysmotility following this treatment. The aims of the present study were to investigate gastrointestinal symptoms among patients with endometriosis and to examine whether symptoms were associated with menstruation, localization of endometriosis lesions, or treatment with either opioids or GnRH analogs, and if hormonal treatment affected the symptoms. METHODS: All patients with diagnosed endometriosis at the Department of Gynecology were invited to participate in the study. Gastrointestinal symptoms were registered using the Visual Analogue Scale for Irritable Bowel Syndrome (VAS IBS); socioeconomic and medical histories were compiled using a clinical data survey. Data were compared to a control group from the general population. RESULTS: A total of 109 patients and 65 controls were investigated. Compared to controls, patients with endometriosis experienced significantly aggravated abdominal pain (P = 0.001), constipation (P = 0.009), bloating and flatulence (P = 0.000), defecation urgency (P = 0.010), and sensation of incomplete evacuation (P = 0.050), with impaired psychological well-being (P = 0.005) and greater intestinal symptom influence on their daily lives (P = 0.001). The symptoms were not associated with menstruation or localization of endometriosis lesions, except increased nausea and vomiting (P = 0.010) in patients with bowel-associated lesions. Half of the patients were able to differentiate between abdominal pain from endometriosis and from the gastrointestinal tract. Patients using opioids experienced more severe symptoms than patients not using opioids, and patients with current or previous use of GnRH analogs had more severe abdominal pain than the other patients (P = 0.024). Initiation of either combined oral contraceptives or progesterone for endometriosis had no effect on gastrointestinal symptoms when the patients were followed prospectively. CONCLUSIONS: The majority of endometriosis patients experience more severe gastrointestinal symptoms than controls. A poor association between symptoms and lesion localization was found, indicating existing comorbidity between endometriosis and irritable bowel syndrome (IBS). Treatment with opioids or GnRH analogs is associated with aggravated gastrointestinal symptoms. PMID- 26272804 TI - Efficient Dye-Sensitized Solar Cells Made from High Catalytic Ability of Polypyrrole@Platinum Counter Electrode. AB - Polypyrrole@platinum (PPy@Pt) composite film was successfully synthesized by using a one-step electrochemical method and served as counter electrode (CE) for efficient dye-sensitized solar cells (DSSCs). The PPy@Pt CE with one-dimensional structure exhibited excellent electrocatalytic activity and superior charge transfer resistance for I(-)/I3 (-) electrolyte after being the cyclic voltammetry and electrochemical impedance spectroscopy tested. The photocurrent photovoltage curves were further used to calculate the theoretical photoelectric performance parameters of the DSSCs. The DSSC based on the PPy@Pt CE achieved a remarkable power conversion efficiency of 7.35 %, higher about 19.9 % than that of conventional Pt CE (6.13 %). This strategy provides a new opportunity for fabricating low-cost and highly efficient DSSCs. PMID- 26272805 TI - Sleep medicine education and knowledge among undergraduate dental students in Middle East universities. AB - OBJECTIVES: The aim of this study was to assess the undergraduate dental education in sleep medicine in Middle East universities as well as the students' knowledge in this field. METHODS: A cross-sectional observational study was carried out during the period from September 2013 to April 2014.Two different questionnaires were used. A self-administered questionnaire and a cover letter were emailed and distributed to 51 randomly selected Middle East dental schools to gather information about their undergraduate sleep medicine education offered in the academic year 2012-2013.The second questionnaire was distributed to the fifth-year dental students in the 2nd Sharjah International Dental Student Conference in April 2014, to assess their knowledge on sleep medicine. A survey to assess knowledge of sleep medicine in medical education (Modified ASKME Survey) was used. RESULTS: Thirty-nine out of 51 (76%) responded to the first questionnaire. Out of the responding schools, only nine schools (23%) reported the inclusion of sleep medicine in their undergraduate curriculum. The total average hours dedicated to teaching sleep medicine in the responding dental schools was 1.2 hours. In the second questionnaire, 29.2% of the respondents were in the high score group, whereas 70.8% scored low in knowledge of sleep-related breathing disorders. DISCUSSION: Dental students in Middle East universities receive a weak level of sleep medicine education resulting in poor knowledge in this field. PMID- 26272806 TI - A phase I/II, open-label, randomised study of nintedanib plus mFOLFOX6 versus bevacizumab plus mFOLFOX6 in first-line metastatic colorectal cancer patients. AB - BACKGROUND: This randomised, open-label, phase I/II study evaluated the efficacy and safety of nintedanib, an oral, triple angiokinase inhibitor, combined with chemotherapy, relative to bevacizumab plus chemotherapy as first-line therapy in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients with histologically confirmed mCRC (adenocarcinoma), an Eastern Cooperative Oncology Group performance status <= 2 and adequate organ function were included. Patients were randomised 2:1 to receive nintedanib 150 mg or 200 mg b.i.d. plus mFOLFOX6 (oxaliplatin 85 mg/m(2), l-leucovorin 200 mg/m(2) or d,l-leucovorin 400 mg/m(2), 5-fluoruracil bolus 400 mg/m(2) followed by 2400 mg/m(2), every 2 weeks) or bevacizumab (5 mg/kg every 2 weeks) plus mFOLFOX6. During phase I, patients underwent a 3 + 3 dose-escalation schema to determine the maximum tolerated dose (MTD) of nintedanib in combination with mFOLFOX6. The primary end point was progression-free survival (PFS) rate at 9 months. Objective response (OR) was a secondary end point. RESULTS: The nintedanib recommended phase II dose was 200 mg b.i.d. plus mFOLFOX6 based on safety data from phase I (n = 12). Of 128 patients randomised in the phase II part, 126 received treatment (nintedanib plus mFOLFOX6, n = 85; bevacizumab plus mFOLFOX6, n = 41). PFS at 9 months was 62.1% with nintedanib and 70.2% with bevacizumab [difference: -8.1% (95% confidence interval -27.8 to 11.5)]. Confirmed ORs were recorded in 63.5% and 56.1% of patients in the nintedanib and bevacizumab groups, respectively. The incidence of adverse events (AEs) considered related to treatment was 98.8% with nintedanib and 97.6% with bevacizumab; the incidence of serious AEs was 37.6% with nintedanib and 53.7% with bevacizumab. The pharmacokinetics of nintedanib and the components of mFOLFOX6 were unaffected by their combination. CONCLUSIONS: Nintedanib in combination with mFOLFOX6 showed efficacy as first-line therapy in patients with mCRC with a manageable safety profile and further studies in this population are warranted. PMID- 26272807 TI - Clinical Utility of Enhanced Relative Activity Recovery on Systolic Myocardial Perfusion SPECT: Lessons from PET. AB - SPECT and PET myocardial perfusion images show greater myocardial intensity and homogeneity in systole than diastole because of greater systolic myocardial thickness, less partial volume loss, and enhanced activity recovery. Consequently, conventional myocardial perfusion images obtained from whole cardiac cycles have lower myocardial intensity and greater heterogeneity than systolic images. Considering relative activity distribution on SPECT systolic images may add clinical utility to whole-cycle images and wall motion. METHODS: Patients undergoing coronary angiogram within 4 mo after SPECT myocardial perfusion imaging were reviewed. Images were interpreted by 2 masked interpreters using a 17-segment, 5-point scale to determine summed rest scores (SSS), summed stress scores, and summed difference scores on conventional and systolic images in 603 patients (55.6% no coronary artery disease [no-CAD] and 44.4% CAD). Studies were considered normal when the SSS was less than 4 and summed difference score was less than 2. RESULTS: In the no-CAD group, systolic SSS was lower than SSS from conventional images (2 +/- 2.3 vs. 3 +/- 2.6, P < 0.001). In contrast, SSS derived from systolic and conventional images were not different in the obstructive CAD group (9.1 +/- 7.6 vs. 9.2 +/- 7.4, P = 0.559). When systolic images were considered, true-negative studies increased from 27.2% to 43.3% (P < 0.001) whereas false-positive studies decreased from 28.4% to 12.3% (P < 0.001). True-positive (38% vs. 37.2%, P = 0.505) and false-negative studies (6.5% vs. 7%, P = 0.450) were not significantly changed. Diagnostic accuracy increased from 65.2% to 80.8% (P < 0.001). CONCLUSION: For gated SPECT myocardial perfusion imaging, when relative activity distribution on systolic images was considered, false-positive studies were reduced and diagnostic accuracy was improved. PMID- 26272808 TI - Nanoparticles for Cardiovascular Imaging and Therapeutic Delivery, Part 1: Compositions and Features. AB - Imaging agents made from nanoparticles are functionally versatile and have unique properties that may translate to clinical utility in several key cardiovascular imaging niches. Nanoparticles exhibit size-based circulation, biodistribution, and elimination properties different from those of small molecules and microparticles. In addition, nanoparticles provide versatile platforms that can be engineered to create both multimodal and multifunctional imaging agents with tunable properties. With these features, nanoparticulate imaging agents can facilitate fusion of high-sensitivity and high-resolution imaging modalities and selectively bind tissues for targeted molecular imaging and therapeutic delivery. Despite their intriguing attributes, nanoparticulate imaging agents have thus far achieved only limited clinical use. The reasons for this restricted advancement include an evolving scope of applications, the simplicity and effectiveness of existing small-molecule agents, pharmacokinetic limitations, safety concerns, and a complex regulatory environment. This review describes general features of nanoparticulate imaging agents and therapeutics and discusses challenges associated with clinical translation. A second, related review to appear in a subsequent issue of JNM highlights nuclear-based nanoparticulate probes in preclinical cardiovascular imaging. PMID- 26272809 TI - Discrimination Between Brown and White Adipose Tissue Using a 2-Point Dixon Water Fat Separation Method in Simultaneous PET/MRI. AB - The purpose of the study was to evaluate signal-fat-fraction (SFF) analysis based on a 2-point-Dixon water-fat separation method in whole-body simultaneous PET/MR imaging for identifying brown adipose tissue (BAT) and discriminating it from white adipose tissue (WAT) using cross-validation via PET. METHODS: This retrospective, internal review board-approved study evaluated 66 PET/MR imaging examinations of 33 pediatric patients (mean age, 14.7 y; range, 7.4-21.4 y). Eleven elderly patients were evaluated as controls (mean age, 79.9 y; range, 76.3 88.6 y). Pediatric patients were divided into 2 groups: with and without metabolically active supraclavicular BAT. The standard of reference for the presence of BAT was at least 1 PET examination showing (18)F-FDG uptake. PET/MR imaging included a 2-point Dixon water-fat separation method. Signal intensities in regions of interest on fat and water images and mean standardized uptake values (SUVmean) were determined bilaterally in supraclavicular and gluteal fat depots. SFF was calculated from the ratio of fat signal over summed water and fat signal. Statistical analysis was conducted using the Student t test and correlation analysis. RESULTS: SFF was significantly lower (P < 0.0001) in supraclavicular BAT than gluteal WAT in all pediatric subjects. Supraclavicular SFF was significantly higher in the control than in the pediatric group (P < 0.0001). In PET-positive patients with multiple examinations, SFF stayed stable whereas SUVmean fluctuated (median intraindividual change, 5% vs. 91%). No significant correlation between SUVmean and SFF could be observed for BAT. CONCLUSION: The results demonstrate that MR imaging-SFF analysis is a reproducible imaging modality for the detection of human BAT and discrimination from WAT. SFF values of BAT are independent from its metabolic activity, making SFF a more reliable parameter for BAT than the commonly used PET signal. However, with the intent to investigate both the composition of BAT and its activation status, hybrid PET/MR imaging might provide supplemental information. PMID- 26272811 TI - Impact of Image-Derived Input Function and Fit Time Intervals on Patlak Quantification of Myocardial Glucose Uptake in Mice. AB - Limited blood volume in mice precludes repeated sampling, rendering a reliable image-derived input function (IDIF) desirable for quantification of glucose uptake. We aimed to compare different IDIF volumes and to evaluate the effects of changing fit time interval on Patlak uptake kinetics in hearts of healthy mice. METHODS: C57BL/6 mice (n=27) were studied under a range of metabolic conditions: no intervention (ctl), overnight fasting, insulin and glucose (6 mU/g, 1 mg/g) under isoflurane, and under ketamine-xylazine anesthesia to suppress glucose uptake. Dynamic PET imaging with 18F-FDG (7.7+/-0.9 MBq) was conducted. Images were analyzed using left ventricle cavity, left atrial cavity, or inferior vena cava as the IDIF. Patlak analysis was conducted using variable fit time intervals: automated fit, fit from 10 to 60 min (late), fit from 2 to 30 min (early), or fit from 2 to 10 min (very early). RESULTS: Both the ventricle and the atrial cavities displayed spill-in from the myocardium in late frames as compared with the vena cava (percentage injected dose per gram, ctl: 21.4+/-6.1 vs. 10.0+/-3.9 vs. 2.5+/-0.3, P<0.001). Higher and more rapid passage of peak activity was observed in the vena cava, but the area under the curve over 2 min was similar. The Patlak slope was significantly higher for the vena cava than atrial IDIF (mL/g/min, ctl: 0.11+/-0.02 vs. 0.07+/-0.01; fasting: 0.09+/-0.03 vs. 0.06+/-0.02; insulin: 0.52+/-0.09 vs. 0.23+/-0.12; ketamine-xylazine: 0.001+/ 0.001 vs. 0.002+/-0.002; P<0.01). The rate of glucose uptake was similarly elevated depending on the IDIF (P<0.01). The various IDIF Patlak values were significantly correlated (r=0.867, P<0.001). Automated fit performed reliably in untreated, fasted, and ketamine-xylazine-treated mice, with no statistical difference compared with late, early, or very early fits. The Patlak composite rate constant (Ki) was markedly underestimated with automated and late fit after acute insulin treatment, reflecting the rapid early 18F-FDG uptake. CONCLUSION: The choice of IDIF has a profound effect on Patlak kinetics and calculated 18F FDG uptake. Adjustment of the time interval for fit may be necessary for accurate calculations, particularly with acute insulin treatment. Even without partial volume correction, the inferior vena cava provides a reliable and reproducible IDIF for Patlak analysis of myocardial glucose uptake in mice. PMID- 26272810 TI - Decreased Nicotinic Receptor Availability in Smokers with Slow Rates of Nicotine Metabolism. AB - The nicotine metabolite ratio (NMR), a stable measure of hepatic nicotine metabolism via the CYP2A6 pathway and total nicotine clearance, is a predictive biomarker of response to nicotine replacement therapy, with increased quit rates in slower metabolizers. Nicotine binds directly to nicotinic acetylcholine receptors (nAChRs) to exert its psychoactive effects. This study examined the relationship between NMR and nAChR (alpha4beta2* subtype) availability using PET imaging of the radiotracer 2-(18)F-fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2 (18)F-FA-85380, or 2-(18)F-FA). METHODS: Twenty-four smokers-12 slow metabolizers (NMR < 0.26) and 12 normal metabolizers (NMR >= 0.26)-underwent 2-(18)F-FA-PET brain imaging after overnight nicotine abstinence (18 h before scanning), using a validated bolus-plus-infusion protocol. Availability of nAChRs was compared between NMR groups in a priori volumes of interest, with total distribution volume (VT/fP) being the measure of nAChR availability. Cravings to smoke were assessed before and after the scans. RESULTS: Thalamic nAChR alpha4beta2* availability was significantly reduced in slow nicotine metabolizers (P = 0.04). Slow metabolizers exhibited greater reductions in cravings after scanning than normal metabolizers; however, craving was unrelated to nAChR availability. CONCLUSION: The rate of nicotine metabolism is associated with thalamic nAChR availability. Additional studies could examine whether altered nAChR availability underlies the differences in treatment response between slow and normal metabolizers of nicotine. PMID- 26272813 TI - Neoadjuvant Treatment of Nonfunctioning Pancreatic Neuroendocrine Tumors with [177Lu-DOTA0,Tyr3]Octreotate. AB - Pancreatic neuroendocrine tumors (NETs) are rare neoplasms for which surgery has almost the only potential for cure. When surgery is not possible because of tumor size and vascular involvement, neoadjuvant treatment with [(177)Lu DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate) may be an option. METHODS: We studied 29 Dutch patients with a pathology-proven nonfunctioning pancreatic NET treated with (177)Lu-octreotate. All patients had a borderline or unresectable pancreatic tumor (group 1) or oligometastatic disease (defined as <=3 liver metastases) (group 2). Progression-free survival (PFS) was analyzed using the Kaplan-Meier method and Cox proportional hazards modeling. RESULTS: After the treatment with (177)Lu-octreotate, successful surgery was performed in 9 of 29 patients (31%). Six patients had a Whipple procedure, 2 patients had a pylorus preserving pancreaticoduodenectomy, and 1 patient had a distal pancreatectomy and splenectomy. The median PFS was 69 mo for patients with successful surgery and 49 mo for the other patients. For comparison, the median PFS in 90 other patients with a nonfunctioning pancreatic NET with more than 3 liver metastases or other metastases was 25 mo. CONCLUSION: Neoadjuvant treatment with (177)Lu-octreotate is a valuable option for patients with initially unresectable pancreatic NETs. PMID- 26272815 TI - Validity Comparison of Three Dental Methods for Age Estimation Based on Tooth Root Translucency. AB - Age estimation of nonliving subjects plays a very important role in identifying human remains. When adult remains are in question, this process becomes even more complex. Among the numerous dental methods that exist for adults aging, the evaluation of root translucency is one of the most useful. This study studies the correlation between age and root translucency by investigating monoradicular teeth affected by pathological processes using the equations proposed by Lamendin, Prince & Ubelaker and from Singhal et al. The average age values calculated according to the three methods were compared with the values of known age. Age estimation using the Student's t-test resulted as more accurate in the methods by Singhal et al. and by Prince & Ubelaker, with respect to that of Lamendin. Age estimation based solely on the percentage of radicular dentinal translucency has been found to be more accurate when diseased teeth are involved. PMID- 26272812 TI - In Vivo Imaging of Natural Killer Cell Trafficking in Tumors. AB - Natural killer cells (NKs) are important effectors of the innate immune system, with marked antitumor activity. Imaging NK trafficking in vivo may be relevant to following up the efficacy of new therapeutic approaches aiming at increasing tumor-infiltrating NKs (TINKs). The specific aims of present study were to efficiently target NKs using a 99mTc-anti-CD56 and to image human NK trafficking in SCID mice bearing human cancer. METHODS: The anti-CD56 monoclonal antibody (mAb) was radiolabeled with 99mTc, and in vitro quality controls were performed to test labeling efficiency, stability, and binding affinity to CD56. In vivo biodistribution was determined by injecting 5.5 MBq (104 ng) of radiolabeled antibody in the tail vein of SCID mice, which were then sacrificed at 1, 3, 6, and 24 h after injection. Targeting experiments were performed on 2 groups of SCID mice inoculated subcutaneously with increasing numbers of human NKs in the right thigh (from 2.5*10(6) to 40*10(6)) and human granulocytes (CD56-) or anaplastic thyroid cancer (ARO) cells in the contralateral thigh as control. TINK trafficking imaging was achieved by injecting 5.5 MBq of 99mTc-anti-CD56 mAb in SCID mice bearing ARO tumor xenografts in the right thigh, 24 h after being reconstituted with 10(5), 10(6), or 10(7) human NKs. RESULTS: Anti-CD56 mAb was radiolabeled, achieving a radiochemical purity of more than 97% and a specific activity of 3,700 MBq/mg and retaining biochemical integrity and binding activity. In vivo studies revealed physiologic uptake in the liver and kidneys. Targeting experiments confirmed the specificity of labeled antibody to CD56+ cells. Human NK cells injected in CD1 nude mice accumulated in the ARO tumors within 24 h and were imaged as early as 3 h after intravenous administration of (99m)Tc-anti-CD56. CONCLUSION: 99mTc-anti-CD56 is a promising tool for in vivo imaging of TINK cell trafficking. PMID- 26272814 TI - Administration of Radioactive Iodine Therapy Within 1 Year After Total Thyroidectomy Does Not Affect Vocal Function. AB - The purpose of this study was to evaluate the impact of radioactive iodine therapy (RIT) on vocal function during the early follow-up period after total thyroidectomy (TT) using perceptive and objective measurements, questionnaires regarding subjective symptoms, and data on vocal function in a prospectively enrolled and serially followed thyroid cancer cohort. METHODS: Of 212 patients who underwent TT and were screened between January and December 2010 at our hospital, 160 were included in the final analysis. Patients with the following histories were excluded: lateral neck dissection, organic vocal fold disease, external radiotherapy, and voice evaluation during thyroxine withdrawal. Patients were stratified into 3 groups: TT, TT with low-dose RIT (1.1-2.2 GBq), and TT with high-dose RIT (>=3.7 GBq). Voice evaluations were performed before surgery and at 1, 6, and 12 mo after TT. RESULTS: Vocal characteristics were altered after TT, including changes on the grade, roughness, and strain scale; increased amplitude perturbation; decreased fundamental frequency; narrowed pitch range; and global disturbances in subjective functional parameters on the voice handicap index. However, the degree of vocal changes among the 3 groups did not significantly differ within the 1-y postoperative follow-up period. According to the results of subgroup analyses of patients who demonstrated good voice outcomes after TT, there were no significant functional differences among the 3 groups. CONCLUSION: RIT at any dose does not affect vocal function within 1 y of TT. PMID- 26272816 TI - Surgical Ventricular Septal Myectomy for Patients With Noonan Syndrome and Symptomatic Left Ventricular Outflow Tract Obstruction. AB - Approximately 20% to 30% of patients with Noonan syndrome (NS) have asymmetric left ventricular hypertrophy (LVH) and LV outflow tract obstruction (LVOTO). The role of surgical myectomy in such patients is unknown. We sought to compare clinical features and outcomes of patients with NS and LVOTO with age- and gender matched patients with nonsyndromic, obstructive hypertrophic cardiomyopathy (HC) after myectomy. Two cohorts were selected and retrospectively analyzed using Mayo Clinic databases from 1996 to 2014. Subjects included patients with NS with LVH and LVOTO and nonsyndromic controls with obstructive HC. Twenty-three patients with NS and LVH were identified, of whom 12 (8 males) underwent myectomy (10 septal and 2 combined septal/apical) for severe LVOTO (10 pediatric and 2 adults; 13 +/- 10 year old [range 1 to 39]). Similar echocardiographic improvements were noted in both groups. There were no perioperative deaths. Residual gradients were slightly higher in patients with NS. No improvement was noted in left atrial volume after myectomy in patients with NS. At early follow-up, the majority showed improvement in the New York Heart Association class (88% in NS vs 82% in HC, median of 6 and 2 months, respectively). At late follow-up (median of 7 years), the survival rate was 92% in NS and 100% in HC. In patients with NS with LVH and symptomatic LVOTO, myectomy reduces both gradient and the New York Heart Association class, similar to patients with nonsyndromic obstructive HC. Residual gradients were slightly higher, and left atrial dilation persisted in patients with NS. In conclusion, myectomy should be considered in patients older than 1 year with NS and symptomatic LVOTO. PMID- 26272817 TI - Mechanical forces regulate the interactions of fibronectin and collagen I in extracellular matrix. AB - Despite the crucial role of extracellular matrix (ECM) in directing cell fate in healthy and diseased tissues--particularly in development, wound healing, tissue regeneration and cancer--the mechanisms that direct the assembly and regulate hierarchical architectures of ECM are poorly understood. Collagen I matrix assembly in vivo requires active fibronectin (Fn) fibrillogenesis by cells. Here we exploit Fn-FRET probes as mechanical strain sensors and demonstrate that collagen I fibres preferentially co-localize with more-relaxed Fn fibrils in the ECM of fibroblasts in cell culture. Fibre stretch-assay studies reveal that collagen I's Fn-binding domain is responsible for the mechano-regulated interaction. Furthermore, we show that Fn-collagen interactions are reciprocal: relaxed Fn fibrils act as multivalent templates for collagen assembly, but once assembled, collagen fibres shield Fn fibres from being stretched by cellular traction forces. Thus, in addition to the well-recognized, force-regulated, cell matrix interactions, forces also tune the interactions between different structural ECM components. PMID- 26272818 TI - Loss of primary cilia correlates with cytologic severity in dysplastic melanocytic nevi. AB - BACKGROUND: Primary cilia are ubiquitously present in cell surface organelles with essential functions in cellular proliferation, differentiation and development. We have previously shown that cilia in melanoma in situ, invasive melanoma and metastatic melanoma are nearly completely lost, whereas benign nevi are ciliated. Dysplastic nevi (DN) have a wide range of histopathologic features from mild (low-grade) to severe (high-grade) cytologic atypia and represent a key clinical and histopathologic marker for melanomagenesis. We sought to identify whether cilia are retained in these melanocytic lesions and whether increasing degree of dysplasia correlates with loss of ciliation. METHODS: We measured the percentage of ciliated melanocytes (ciliation index) in DN with mild (n = 9) and severe dysplasia (n = 10). We identified the primary cilium and basal bodies by immunofluorescence staining of sections with acetylated alpha-tubulin and gamma tubulin, respectively. RESULTS: Our results showed a significant decrease in the ciliation index from mild dysplastic (55%) to severe DN (14%) (p = 0.005). CONCLUSIONS: These data support the hypothesis that primary cilium loss may play a role in the underlying biology of severe DN. The ciliation index is a novel quantitative tool that may increase the reproducibility in grading severity of dysplasia for diagnostic and clinical management of melanocytic neoplasms. PMID- 26272819 TI - Sequential replication-coupled destruction at G1/S ensures genome stability. AB - Timely ubiquitin-mediated protein degradation is fundamental to cell cycle control, but the precise degradation order at each cell cycle phase transition is still unclear. We investigated the degradation order among substrates of a single human E3 ubiquitin ligase, CRL4(Cdt2), which mediates the S-phase degradation of key cell cycle proteins, including Cdt1, PR-Set7, and p21. Our analysis of synchronized cells and asynchronously proliferating live single cells revealed a consistent order of replication-coupled destruction during both S-phase entry and DNA repair; Cdt1 is destroyed first, whereas p21 destruction is always substantially later than that of Cdt1. These differences are attributable to the CRL4(Cdt2) targeting motif known as the PIP degron, which binds DNA-loaded proliferating cell nuclear antigen (PCNA(DNA)) and recruits CRL4(Cdt2). Fusing Cdt1's PIP degron to p21 causes p21 to be destroyed nearly concurrently with Cdt1 rather than consecutively. This accelerated degradation conferred by the Cdt1 PIP degron is accompanied by more effective Cdt2 recruitment by Cdt1 even though p21 has higher affinity for PCNA(DNA). Importantly, cells with artificially accelerated p21 degradation display evidence of stalled replication in mid-S phase and sensitivity to replication arrest. We therefore propose that sequential degradation ensures orderly S-phase progression to avoid replication stress and genome instability. PMID- 26272822 TI - Erratum: Targeted disruption of a single sex pheromone receptor gene completely abolishes in vivo pheromone response in the silkmoth. PMID- 26272821 TI - Effects of non-surgical factors on digital replantation survival rate: a meta analysis. AB - This study aimed to evaluate the risk factors affecting survival rate of digital replantation by a meta-analysis. A computer retrieval of MEDLINE, OVID, EMBASE, and CNKI databases was conducted to identify citations for digital replantation with digit or finger or thumb or digital or fingertip and replantation as keywords. RevMan 5.2 software was used to calculate the pooled odds ratios. In total, there were 4678 amputated digits in 2641 patients. Gender and ischemia time had no significant influence on the survival rate of amputation replantation (P > 0.05). Age, injured hand, injury type, zone, and the method of preservation the amputated digit significantly influence the survival rate of digital replantation (P < 0.05). Children, right hand, crush, or avulsion and little finger are the risk factors that adversely affect the outcome. THE LEVEL OF EVIDENCE: Level 5*. PMID- 26272820 TI - Neurofibromatosis-1 regulation of neural stem cell proliferation and multilineage differentiation operates through distinct RAS effector pathways. AB - Neurofibromatosis type 1 (NF1) is a common neurodevelopmental disorder caused by impaired function of the neurofibromin RAS regulator. Using a combination of Nf1 genetically engineered mice and pharmacological/genetic inhibition approaches, we report that neurofibromin differentially controls neural stem cell (NSC) proliferation and multilineage differentiation through the selective use of the PI3K/AKT and RAF/MEK pathways. While PI3K/AKT governs neurofibromin-regulated NSC proliferation, multilineage differentiation is MEK-dependent. Moreover, whereas MEK-regulated multilineage differentiation requires Smad3-induced Jagged-1 expression and Notch activation, MEK/Smad3-regulated Hes1 induction is only responsible for astrocyte and neuronal differentiation. Collectively, these findings establish distinct roles for the RAS effector pathways in regulating brain NSC function. PMID- 26272823 TI - Growth characteristics of Lactobacillus brevis KB290 in the presence of bile. AB - Live Lactobacillus brevis KB290 have several probiotic activities, including immune stimulation and modulation of intestinal microbial balance. We investigated the adaptation of L. brevis KB290 to bile as a mechanism of intestinal survival. Strain KB290 was grown for 5 days at 37 degrees C in tryptone-yeast extract-glucose (TYG) broth supplemented with 0.5% sodium acetate (TYGA) containing 0.15%, 0.3%, or 0.5% bile. Growth was determined by absorbance at 620 nm or by dry weight. Growth was enhanced as the broth's bile concentration increased. Bile-enhanced growth was not observed in TYG broth or with xylose or fructose as the carbon source, although strain KB290 could assimilate these sugars. Compared with cells grown without bile, cells grown with bile had twice the cell yield (dry weight) and higher hydrophobicity, which may improve epithelial adhesion. Metabolite analysis revealed that bile induced more lactate production by glycolysis, thus enhancing growth efficiency. Scanning electron microscopy revealed that cells cultured without bile for 5 days in TYGA broth had a shortened rod shape and showed lysis and aggregation, unlike cells cultured for 1 day; cells grown with bile for 5 days had an intact rod shape and rarely appeared damaged. Cellular material leakage through autolysis was lower in the presence of bile than in its absence. Thus lysis of strain KB290 cells cultured for extended periods was suppressed in the presence of bile. This study provides new role of bile and sodium acetate for retaining an intact cell shape and enhancing cell yield, which are beneficial for intestinal survival. PMID- 26272824 TI - EASL Recognition Award Recipient 2015: Prof. Roberto de Franchis. PMID- 26272825 TI - Structural insights into the O2 reduction mechanism of multicopper oxidase. AB - Multicopper oxidases are ubiquitous enzymes that catalyse the oxidation of various substrates via the reduction of O2 to H2O. The enzymes contain a common active centre consisting of four copper ions. The key component for O2 reduction is the trinuclear copper centre comprising one type II and a pair of type III copper ions. Although the crystal structures of many multicopper oxidases have been determined by X-ray crystallography, the geometric parameters in the trinuclear copper centre are different for each study. Recent studies have revealed that the redox state of copper ions is altered by X-ray irradiation. The reported crystal structures may represent mixtures of different stages of the catalytic reactions. In this review, we discuss recent findings related to the structure of the active site in multicopper oxidases. PMID- 26272826 TI - Response to Letter by Dr. Lipetz. PMID- 26272827 TI - NMR structural characterization of the N-terminal active domain of the gyrase B subunit from Pseudomonas aeruginosa and its complex with an inhibitor. AB - The N-terminal ATP binding domain of the DNA gyrase B subunit is a validated drug target for antibacterial drug discovery. Structural information for this domain (pGyrB) from Pseudomonas aeruginosa is still missing. In this study, the interaction between pGyrB and a bis-pyridylurea inhibitor was characterized using several biophysical methods. We further carried out structural analysis of pGyrB using NMR spectroscopy. The secondary structures of free and inhibitor bound pGyrB were obtained based on backbone chemical shift assignment. Chemical shift perturbation and NOE experiments demonstrated that the inhibitor binds to the ATP binding pocket. The results of this study will be helpful for drug development targeting P. aeruginosa. PMID- 26272828 TI - Redox-coupled structural changes of the catalytic a' domain of protein disulfide isomerase. AB - Protein disulfide isomerase functions as a folding catalyst in the endoplasmic reticulum. Its b' and a' domains provide substrate-binding sites and undergo a redox-dependent domain rearrangement coupled to an open-closed structural change. Here we determined the first solution structure of the a' domain in its oxidized form and thereby demonstrate that oxidation of the a' domain induces significant conformational changes not only in the vicinity of the active site but also in the distal b'-interfacial segment. Based on these findings, we propose that this conformational transition triggers the domain segregation coupled with the exposure of the hydrophobic surface. PMID- 26272831 TI - Shaping the Future of Cognitive Science. AB - For further resources related to this article, please visit the WIREs website. PMID- 26272830 TI - A case study of air quality above an urban roof top vegetable farm. AB - The effect of elevation and rooftop configuration on local air quality was investigated at the Brooklyn Grange rooftop farm during a short-term observational campaign. Using multiple particle counters and sonic anemometers deployed along vertical gradients, we found that PM2.5 concentration decayed with height above the street. Samples adjacent to the street had the highest average PM2.5 concentration and frequent stochastic spikes above background. Rooftop observations 26 m above ground showed 7-33% reductions in average PM2.5 concentration compared with the curbside and had far fewer spikes. A relationship between the vertical extinction rate of PM2.5 and atmospheric stability was found whereby less unstable atmosphere and greater wind shear led to greater PM2.5 extinction due to damped vertical motion of air. PMID- 26272832 TI - The gestural origins of language. AB - The idea that language evolved from manual gestures rather than primate calls dates back at least to the 18th century, and was revived in modern form by the anthropologist, Gordon W. Hewes, in 1973. The main sources of current evidence are: (1) Signed languages invented by deaf communities share with speech the essential characteristics of language, including such properties as reference, generativity, grammar, and prosody; (2) Great apes in captivity are much better able to learn intentional communication systems based on manual gestures than to acquire speech; (3) The manual gestures of chimpanzees in the wild are more flexible and context-independent than their vocalizations; (4) The mirror system in the primate brain provides a natural platform for the evolution of language; it represents manual gestures and some nonvocal oral movements, but not vocalizations. Vocal gestures were probably incorporated into the mirror system late in hominin evolution, perhaps only with the emergence of our own species, Homo sapiens. Copyright (c) 2009 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26272833 TI - Deductive reasoning. AB - This article begins with an account of logic, and of how logicians formulate formal rules of inference for the sentential calculus, which hinges on analogs of negation and the connectives if, or, and and. It considers the various ways in which computer scientists have written programs to prove the validity of inferences in this and other domains. Finally, it outlines the principal psychological theories of how human reasoners carry out deductions. Copyright (c) 2009 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26272829 TI - E. coli MG1655 modulates its phospholipid composition through the cell cycle. AB - This paper describes a study of the phospholipid profile of Escherichia coli MG1655 cultures at the B and D periods of the cell cycle. The results indicate that the phosphatidyl glycerol fraction grows relatively rapidly and that the size of the cardiolipin (CL) fraction does not grow at all during cell elongation. This is consistent with observations that CL is located preferentially at the poles of E. coli. It also suggests that lipid production is controlled as a function of the cell cycle. PMID- 26272834 TI - Neurolaw. AB - Less than three decades ago, the fields of cognitive psychology and neuroscience joined forces to form cognitive neuroscience. More recently, neuroscience has combined with social psychology and with economics to produce social neuroscience and neuroeconomics. Each of these amalgamations has been revolutionary in its own way. Neurolaw extends this trend. Copyright (c) 2009 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26272835 TI - Comparative cultural cognition. AB - Cultural learning is an adaptive mechanism which can lead to changes in behavior and cognition much faster than naturally selected genetic change. Although social learning is prevalent in many species, the capacity for significant cumulative culture remains restricted to humans. This capacity has been a driving force behind the evolution of complexity in our technologies and societies, and has allowed us to become the most widespread mammal on earth. The comparative study of cultural cognition assesses where important differences lie between species. A combination of observational studies in the wild, experimental studies in captivity, and field experiments together provide the most comprehensive methods with which to tackle the question. Copyright (c) 2009 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26272836 TI - Representation, philosophical issues about. AB - The concept of representation plays a central role in philosophical and scientific theorizing about the mind, and according to the representational theory of mind (RTM), a wide variety of cognitive and perceptual capacities are best explained in terms of the occurrence and processing of mental representations. The concept of representation remains elusive, however, and there is no widespread agreement among philosophers or cognitive scientists over what it is for one thing to represent another. One reason for the lack of consensus is that philosophers and scientists deploy the concept in many different ways for many different purposes. Another reason for the lack of consensus is that, while it is generally agreed that a scientifically useful notion of representation should be informed and constrained by what we know about brains, there is disagreement over what contemporary neuroscience does or does not suggest about the nature of representation. This article discusses some of the key issues involved in developing a general theory of mental representation, in light of these divergent purposes and conflicting views. Copyright (c) 2009 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26272837 TI - Government-binding/principles and parameters theory. AB - Principles and Parameters Theory is an approach to the study of the human language capacity based on an abstract underlying representation and operations called 'transformations' successively altering that structure. It has gradually evolved from the Government and Binding Theory to the Minimalist Program. Copyright (c) 2009 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26272838 TI - Attention and consciousness. AB - For the past three decades there has been a substantial amount of scientific evidence supporting the view that attention is necessary and sufficient for perceptual representations to become conscious (i.e., for there to be something that it is like to experience a representational perceptual state). This view, however, has been recently questioned on the basis of some alleged counterevidence. In this paper we survey some of the most important recent findings. In doing so, we have two primary goals. The first is descriptive: we provide a literature review for those seeking an understanding of the present debate. The second is editorial: we suggest that the evidence alleging dissociations between consciousness and attention is not decisive. Thus, this is an opinionated overview of the debate. By presenting our assessment, we hope to bring out both sides in the debate and to underscore that the issues here remain matters of intense controversy and ongoing investigation. Copyright (c) 2009 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26272839 TI - Social neuroscience. AB - Social species, by definition, create emergent organizations beyond the individual that range in humans from dyads, families, and groups to cities, civilizations, and cultures. These emergent structures evolved hand-in-hand with neural, hormonal, and genetic mechanisms to support them because the consequent social behaviors helped these organisms survive, reproduce, and care for offspring sufficiently long that they too survived to reproduce. Social neuroscience is concerned with investigating these emergent structures and the underlying neural, hormonal, and genetic mechanisms that make them possible. As such, it represents an interdisciplinary approach devoted to understanding how biological systems implement social processes and behavior, and to using biological concepts and methods to inform and refine theories of social processes and behavior. Copyright (c) 2009 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26272840 TI - Categorical perception. AB - Categorical perception (CP) is the phenomenon by which the categories possessed by an observer influences the observers' perception. Experimentally, CP is revealed when an observer's ability to make perceptual discriminations between things is better when those things belong to different categories rather than the same category, controlling for the physical difference between the things. We consider several core questions related to CP: Is it caused by innate and/or learned categories, how early in the information processing stream do categories influence perception, and what is the relation between ongoing linguistic processing and CP? CP for both speech and visual entities are surveyed, as are computational and mathematical models of CP. CP is an important phenomenon in cognitive science because it represents an essential adaptation of perception to support categorizations that an organism needs to make. Sensory signals that could be linearly related to physical qualities are warped in a nonlinear manner, transforming analog inputs into quasi-digital, quasi-symbolic encodings. Copyright (c) 2009 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26272841 TI - Risk attitude and preference. AB - Citizens of Western countries are asked to make an increasing number of decisions that involve risk, from decisions about how much and how to save for their old age to choices among medical treatments and medical insurance plans. At the same time, uncertainty about choice outcomes has gone up as the result of ever faster social, environmental, and technological change. Accuracy in predicting what choices people will make, at least in the aggregate, is an important determinant for the success of public policy interventions. In addition, corporate and public policy often tries to influence and modify people's choices in the face of risk and uncertainty, for example, getting people to save more of their income or getting women to invest in less conservative instruments. Understanding the processes that underlie risky decisions and the drivers of risk taking is critical to both agendas. Copyright (c) 2009 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26272842 TI - Animal learning. AB - Pavlov and Thorndike pioneered the experimental study of animal learning and provided psychologists with powerful tools to unveil its underlying mechanisms. Today's research developments and theoretical analyses owe much to the pioneering work of these early investigators. Nevertheless, in the evolution of our knowledge about animal learning, some initial conceptions have been challenged and revised. We first review the original experimental procedures and findings of Pavlov and Thorndike. Next, we discuss critical research and consequent controversies which have greatly shaped animal learning theory. For example, although contiguity seemed to be the only condition that is necessary for learning, we now know that it is not sufficient; the conditioned stimulus (CS) also has to provide information about the occurrence of the unconditioned stimulus (US). Also, animals appear to learn different things about the same stimuli when circumstances vary. For instance, when faced with situations in which the meaning of a CS changes, as in the case of acquisition and later extinction, animals seem to preserve the original knowledge (CS-US) in addition to learning about the new conditions (CS-noUS). Finally, we discuss how parallels among Pavlovian conditioning, operant conditioning, and human causal judgment suggest that causal knowledge may lie at the root of both human and animal learning. All of these empirical findings and theoretical developments prove that animal learning is more complex and intricate than was once imagined. Copyright (c) 2009 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26272843 TI - Episodic memory versus episodic foresight: Similarities and differences. AB - There are logical and empirical grounds that link episodic memory and the ability to imagine future events. In some sense, both episodic memory and episodic foresight may be regarded as two sides of the same capacity to travel mentally in time. After reviewing some of the recent evidence for commonalities, I discuss limits of these parallels. There are fundamental differences between thinking about past and future events that need to be kept in clear view if we are to make progress in understanding the nature of mental time travel. The reviewed evidence suggests that mental time travel is based on a complex system selected not for accuracy about past and future per se, but for fitness benefits. Functional analyses promise to lead to fruitful avenues for future research. Copyright (c) 2009 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26272844 TI - Brain injury: recovery and rehabilitation. AB - This paper discusses contributing factors relating to recovery and rehabilitation among patients who have sustained nonprogressive brain injury. Following a brief description of conditions observed in people with brain damage and their incidence and prevalence, the paper then focuses on survivors of traumatic brain injury (TBI), concentrating particularly on recovery and rehabilitation within this group. As recovery means different things to different people, the term is used here to mean partial recovery of function together with substitution of function.1 Consideration is given to factors influencing recovery from TBI, particularly age, gender, and cognitive reserve. Mechanisms of recovery are also examined, particularly regeneration, diaschisis, and plasticity. Attention is then focused on rehabilitation, a process whereby survivors of brain injury are helped to attain their optimum level of functioning and return to their own most appropriate environments. Cognitive rehabilitation is typically aimed at helping people compensate for their difficulties. The need to treat cognitive, emotional, and psychosocial consequences of brain injury is recognized, and different approaches to rehabilitation are described together with the main changes seen in the past few years. Finally, evidence for the success of neuropsychological rehabilitation is presented. Copyright (c) 2009 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26272845 TI - Attractor networks. AB - An attractor network is a network of neurons with excitatory interconnections that can settle into a stable pattern of firing. This article shows how attractor networks in the cerebral cortex are important for long-term memory, short-term memory, attention, and decision making. The article then shows how the random firing of neurons can influence the stability of these networks by introducing stochastic noise, and how these effects are involved in probabilistic decision making, and implicated in some disorders of cortical function such as poor short term memory and attention, schizophrenia, and obsessive-compulsive disorder. Copyright (c) 2009 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26272846 TI - Development of cross-modal processing. AB - The ability to process and integrate cross-modal input is important for many everyday tasks. The current paper reviews theoretical and empirical work examining cross-modal processing with a focus on recent findings examining infants' and children's processing of arbitrary auditory-visual pairings. The current paper puts forward a potential mechanism that may account for modality dominance effects found in a variety of cognitive tasks. The mechanism assumes that although early processing of auditory and visual input is parallel, attention is allocated in a serial manner with the modality that is faster to engage attention dominating later processing. Details of the mechanism, factors influencing processing of arbitrary auditory-visual pairings, and implications for higher-order tasks are discussed. Copyright (c) 2009 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. PMID- 26272848 TI - [Ameliorer l'experience des patients par la personnalisation des services de sante]. AB - De nombreux leaders trouvent difficile de mobiliser les patients, dont les attentes envers les services de sante exigent desormais une approche plus personnalisee. Le present article porte sur les tendances de consommation qui influent sur la mobilisation et l'autonomisation des patients a l'egard des technologies numeriques. Eclaires par les tendances de consommation et de sante en population susceptibles de personnaliser les services de sante, les leaders peuvent adopter trois strategies pour renforcer l'experience des patients : mettre davantage l'accent sur la sante et le bien-etre personnels, amorcer un virage vers des soins de sante personnalises plutot que normalises et faciliter la democratisation de l'information en matiere de sante. PMID- 26272849 TI - Interventions to Improve Adolescent Vaccination: What May Work and What Still Needs to Be Tested. AB - Since the development of the "adolescent platform" of vaccination in 1997, hundreds of studies have been conducted, identifying barriers to and facilitators of adolescent vaccination. More recent research has focused on developing and evaluating interventions to increase uptake of adolescent vaccines. This review describes a selection of recent intervention studies for increasing adolescent vaccination, divided into three categories: those with promising results that may warrant more widespread implementation, those with mixed results requiring more research, and those with proven effectiveness in other domains that have not yet been tested with regard to adolescent vaccination. PMID- 26272847 TI - Classification systems of communication for use in epidemiological surveillance of children with cerebral palsy. AB - AIM: Children with cerebral palsy (CP) often experience communication difficulties. We aimed to identify a classification system for communication of children with CP suitable for epidemiological surveillance. METHOD: Systems to classify the communication of children with CP were identified. The Communication Function Classification System (CFCS), Functional Communication Classification System (FCCS), and Viking Speech Scale (VSS) were chosen for further investigation and translated. They were administered to 155 children aged 4 to 13 years with CP (across all motor severity levels) from eight European countries. Children's parents/carers, speech therapists, and other health professionals applied the systems through direct observation. Other professionals applied them from case notes only. The systems were assessed for agreement, stability, ease, and feasibility of application. RESULTS: Test-retest stability was moderate-to high for VSS (k=0.66-0.88), CFCS (k=uncomputed-0.91), and FCCS (k=0.52-0.91). Overall interrater agreement was fair to very good for every classification system. VSS achieved the best agreement between parents/carers and speech therapists. VSS was considered the easiest instrument to apply. INTERPRETATION: Because of its ease of use by a range of healthcare professionals, the VSS should be considered for CP registers which intend to survey speech intelligibility. For a wider assessment of communication, the CFCS or FCC should be considered. PMID- 26272850 TI - Cosolvency approach for assessing the solubility of drugs in poly(vinylpyrrolidone). AB - The log-linear cosolvency model was applied for estimating the solubility of four drugs: ritonavir, griseofulvin, itraconazole and ketoconazole in poly(vinylpyrrolidone) (PVP). Cosolvent mixtures consisted of PVP mixed in different proportions with N-ethylpyrrolidone, which served as the monomeric analogue of the repeating unit of the polymer. Solubility in the monomer-polymer mixtures was determined by HPLC. As the configuration of the solvating unit in the solvent mixture changed from entirely monomeric to increasingly polymeric, the solubility of the drugs decreased in a fashion that follows the log-linear cosolvency model. The linear relationship was used to obtain estimates for the solubility of the drugs in the different grades of PVP. The solubility of the drugs in PVP is low (from <1% to ~15% w/w). Among the set of drug solutes, ritonavir exhibited the highest solubility in PVP (w/w). Mixing with the monomer is most favorable for griseofulvin among the four drugs. However, the detrimental effect of polymerization on its solubility is more pronounced than for ritonavir. The mixing of itraconazole with the monomer is more favorable than the mixing of ketoconazole. However, despite the molecular similarity between ketaconazole and itraconazole, the solubility of the latter is particularly affected by the polymeric configuration of the solvating unit, to the point of exhibiting differences in solubility resulting from the chain length of the grade of PVP used. The log-linear cosolvency model is a useful tool for estimating the solubility of the drugs in the polymer at room temperature, while providing quantitative information on the differences in mixing behavior of the four model compounds. PMID- 26272852 TI - Reply to: Letter to the editor on "A comparison of primary and delayed wound closure in severe open tibial fractures initially treated with internal fixation and vacuum-assisted wound coverage: A case-controlled study". PMID- 26272851 TI - Computed Tomography Imaging in Patients with Congenital Heart Disease Part I: Rationale and Utility. An Expert Consensus Document of the Society of Cardiovascular Computed Tomography (SCCT): Endorsed by the Society of Pediatric Radiology (SPR) and the North American Society of Cardiac Imaging (NASCI). AB - This is an expert consensus document created to provide information about the current use of cardiovascular computed tomography (CT) in patients of all ages with proven or suspected congenital heart disease (CHD). The discussion and recommendations are based on available literature and the judgment of a diverse group of subspecialists with extensive experience in the use of CT imaging in CHD. The field of CHD CT imaging is evolving rapidly with the availability of new scanner technology. In addition, the prevalence of palliated CHD has increased with marked improvements in patient survival. We believe it is important to review the clinical indications, strengths, limitations, and risks of cardiovascular CT in this patient population. This is the first of two complementary documents. It will concentrate on the disease entities and circumstances in which CT may be used. The second document will focus on recommendations for the technical performance of cardiovascular CT in patients with CHD. Successful cardiovascular CT imaging of CHD requires an in depth understanding of the core teaching elements of both cardiology and radiology. The ability to perform and interpret high quality congenital cardiovascular CT in a clinical context requires focused time and effort regardless of the previous background of the cardiac imager. This is reflected by a writing committee that consists of pediatric and adult radiologists and cardiologists, all whom have extensive experience in performing CT in this patient population. Cardiovascular CT is complementary to other imaging modalities and its optimal use will be in centers where all diagnostic modalities are available. The choice of modality for an individual patient should be determined by age, diagnosis, clinical condition, clinical question and patient preference.(1-4) Use of CT in CHD should be reserved for situations in which it is expected to provide unique diagnostic information for the individual patient or clinical indication, and/or less risk than other modalities. This multi-disciplinary document is intended to guide the optimal selection of CHD patients for cardiovascular CT. The goals of this document apply to both pediatric and adult CHD patients and are to. PMID- 26272853 TI - A new cholangiojejunostomy for multiple biliary ductal openings: A study in pigs. AB - BACKGROUND: To investigate the safety and feasibility of a new intrahepatic cholangiojejunostomy for multiple intrahepatic biliary ductal openings after hepatobiliary resection. MATERIALS AND METHODS: Forty-eight pigs were randomly assigned into two groups: the new intrahepatic cholangiojejunostomy group (n = 24); and the control group (n = 24) with classical hepaticojejunostomy. Six pigs in each group were sacrificed on postoperative day 7, 30, 90 and 180. The primary outcomes were postoperative mortality, morbidity, and the pathological changes in the anastomoses. The secondary outcomes were levels of aspartate transaminase, bilirubin, albumin and alkaline phosphate. RESULTS: The operations were successfully carried out. The rates of anastomotic leakage and cholangitis in the study group were 0% and 8.3% (2/24), while in the control group they were 4.2% (1/24) and 20.8% (5/24), respectively. The stenotic rates of the sectional areas of the anastomotic stomas in the study group were lower than those in the control group on postoperative day 7, 30, 90 and 180 (p < 0.001, p = 0.002, p < 0.001, and p = 0.001, respectively). Under microscopy, in the study group, the anterior wall of the stoma was everted and sunken while the posterior wall was protruded in a semicircular-disc shaped. The liver transection plane was epithelialized with mucosal covering by post-operative day 30. In the control group, however, the stoma was centripetally protruded with a relative circular stenosis. CONCLUSIONS: The new intrahepatic cholangiojejunostomy is safe, simple, and convenient for multiple biliary ductal openings. PMID- 26272854 TI - Immunogenetics of type 1 diabetes: A comprehensive review. AB - Type 1 diabetes (T1D) results from the autoimmune destruction of insulin producing beta cells in the pancreas. Prevention of T1D will require the ability to detect and modulate the autoimmune process before the clinical onset of disease. Genetic screening is a logical first step in identification of future patients to test prevention strategies. Susceptibility to T1D includes a strong genetic component, with the strongest risk attributable to genes that encode the classical Human Leukocyte Antigens (HLA). Other genetic loci, both immune and non immune genes, contribute to T1D risk; however, the results of decades of small and large genetic linkage and association studies show clearly that the HLA genes confer the most disease risk and protection and can be used as part of a prediction strategy for T1D. Current predictive genetic models, based on HLA and other susceptibility loci, are effective in identifying the highest-risk individuals in populations of European descent. These models generally include screening for the HLA haplotypes "DR3" and "DR4." However, genetic variation among racial and ethnic groups reduces the predictive value of current models that are based on low resolution HLA genotyping. Not all DR3 and DR4 haplotypes are high T1D risk; some versions, rare in Europeans but high frequency in other populations, are even T1D protective. More information is needed to create predictive models for non-European populations. Comparative studies among different populations are needed to complete the knowledge base for the genetics of T1D risk to enable the eventual development of screening and intervention strategies applicable to all individuals, tailored to their individual genetic background. This review summarizes the current understanding of the genetic basis of T1D susceptibility, focusing on genes of the immune system, with particular emphasis on the HLA genes. PMID- 26272855 TI - IL-33 released by alum is responsible for early cytokine production and has adjuvant properties. AB - Human vaccines have used aluminium-based adjuvants (alum) for >80 years despite incomplete understanding of how alum enhances the immune response. Alum can induce the release of endogenous danger signals via cellular necrosis which elicits inflammation-associated cytokines resulting in humoral immunity. IL-33 is proposed to be one such danger signal that is released from necrotic cells. Therefore, we investigated whether there is a role for IL-33 in the adjuvant activity of alum. We show that alum-induced cellular necrosis results in elevated levels of IL-33 following injection in vivo. Alum and IL-33 induce similar increases in IL-5, KC, MCP-1, MIP-1alpha and MIP-1beta; many of which are dependent on IL-33 as shown in IL-33 knockout mice or by using an IL-33 neutralizing recombinant ST2 receptor. Furthermore, IL-33 itself functions as an adjuvant that, while only inducing a marginal primary response, facilitates a robust secondary response comparable to that observed with alum. However, IL-33 is not absolutely required for alum-induced antibody responses since alum mediates similar humoral responses in IL-33 knockout and wild-type mice. Our results provide novel insights into the mechanism of action behind alum-induced cytokine responses and show that IL-33 is sufficient to provide a robust secondary antibody response independently of alum. PMID- 26272857 TI - Randomized controlled trial of self-directed versus in-classroom teaching of narrow-band imaging for diagnosis of Barrett's esophagus-associated neoplasia. AB - BACKGROUND AND AIMS: Previous studies have shown that narrow-band imaging (NBI) can be taught to inexperienced gastroenterologists. However, it is unknown whether in-person training is more effective than self-directed training. The objective of this study was to compare the accuracy of diagnosing Barrett's esophagus (BE)-associated neoplasia by trainees with no prior NBI experience between in-classroom and self-directed didactic training programs. METHODS: This was a randomized controlled trial that took place at 2 tertiary-care medical centers, involving 33 participants--12 second-year medical students, 8 first-year gastroenterology fellows, 7 second-year gastroenterology fellows, and 6 third year gastroenterology fellows. A teaching module was developed for all participants to review. Half of the participants were taught in a classroom setting by an endoscopist with expertise in NBI, whereas the other participants were in a self-directed group that received an automated version of the presentation with audio commentary. Participants completed a test of 40 randomized NBI images, predicting the histology and indicating their confidence levels in the diagnosis. RESULTS: There was no difference in accuracy between the in-classroom and self-directed groups (57.5% vs 57.2%; P = 1.0). The in-classroom group had a significantly higher percentage of high-confidence answers (57.2% vs 41.1%; P <= .01), but there was no significant difference in accuracy with these high-confidence answers (60.7% vs 66.4%; P = .34). There was no significant difference in overall accuracy or accuracy with high-confidence predictions between the 2 study sites (57.4% vs 55.9%, P = .58; 63.1% vs 61.4%, P = .69) or between gastroenterology fellows and medical students (57.8% vs 54.6%, P = .27; 62.8% vs 60.8%, P = .62). CONCLUSIONS: The overall accuracy of predicting NBI patterns in BE were modest in our study participants, and there was no difference between self-directed and in-classroom didactic training. Self-directed learning of NBI is adequate for teaching NBI to trainees. PMID- 26272858 TI - Split-dose sodium picosulfate-magnesium citrate colonoscopy preparation achieves lower residual gastric volume with higher cleansing effectiveness than a previous day regimen. AB - BACKGROUND AND AIMS: It is known that sodium picosulfate-magnesium citrate (SPMC) bowel preparations are effective, well tolerated and safe, and that split-dosing is more effective for colon cleansing than previous-day regimens. Anesthetic guidelines consider that residual gastric fluid is independent of clear liquid fasting times. However, reluctance to use split-dosing persists. This may be due to limited data on residual gastric fluid volumes (RGFVs) and split-dosing bowel preparations, and that these may not be perceived as standard clear liquids. Furthermore, no studies are available on RGFV/residual gastric fluid pH (RGFpH) and SPMC. We aimed to evaluate the cleansing effectiveness and the RGFV/RGFpH achieved after an SPMC split-dosing regimen compared with a SPMC previous-day regimen. METHODS: This was a single-center observational study. A total of 328 outpatients scheduled for simultaneous EGD and colonoscopy and following a split dosing or previous-day regimen of SPMC were included. We prospectively measured colon cleanliness by using the Ottawa Bowel Preparation Scale, RGFV, and RGFpH. RESULTS: Ottawa Bowel Preparation Scale scores for overall, right, mid-colon, and colon fluid were significantly better in the split-dosing group. In the split dosing group, the 3- to 4-hour fasting time consistently achieved the best cleansing quality. RGFV was significantly lower in the split-dosing group (11.09 vs 18.62, P < .001). No significant differences in RGFpH were detected. CONCLUSIONS: Split-dosing SPMC provides higher colon cleansing quality with lower RGFVs than previous-day SPMC regimens. SPMC in split-dosing acts exactly as a standard clear liquid acts, and thus anesthetic guidelines on this issue may be applied with no concerns. PMID- 26272859 TI - Corticosterone combined with intramedial prefrontal cortex infusion of SCH 23390 impairs the strong fear response in high-fear-reactivity rats. AB - Accumulating evidence suggests that stress-dose corticosteroids impair fear memory in animals and humans. Corticosteroid treatment after critical illness is seen as a potential psychotropic medication by which to prevent posttraumatic stress disorder. However, individual difference in the responsiveness to stress (i.e., stress reactivity) is a factor that modulates the efficacy of corticosteroids. To understand the contribution of fear reactivity to the effect of post-stress corticosterone, male Sprague-Dawley rats were subjected to classical tone-cued fear conditioning and separated into high and low reactivity (HR and LR, respectively) responder groups based on their levels of freezing during conditioning. The HR rats showed significantly higher fear responses than the LR rats during conditioning as assessed by freezing behavior. At two intervals, 30 min and 48 hr later, the HR rats still displayed more pronounced conditioned responses to cued stimuli compared with the LR rats. Moreover, in contrast to the LR rats, the enhanced fear response in the HR rats was difficult to attenuate by post-training high-dose corticosterone. These results suggest that fear reactivity results in stronger fear memory, and that it is difficult to disrupt this strong fear memory in the HR phenotype using monotherapy. However, the strong fear memory in the HR rats was impaired by concurrent intramedial prefrontal cortex infusion of a high dose of the dopamine D1 receptor antagonist SCH 23390 and systemic administration of corticosterone. SCH 23390 and corticosterone alone did not decrease freezing levels in the HR rats. The fear impairment induced by SCH 23390 combined with corticosterone was not attributable to the effect of these drugs on locomotor activity. This effect was not found with administration of the D2 antagonist eticlopride combined with corticosterone. Our findings demonstrate that the conditioned fear memory in individuals with high stress reactivity is difficult to disrupt using monotherapy, but that combined pharmacotherapy may be useful for treating intervention-resistant fear. PMID- 26272856 TI - Effect of transgastric natural orifice transluminal endoscopic surgery peritoneoscopy on abdominal organ microcirculation: an experimental controlled study. AB - BACKGROUND AND AIMS: On-demand insufflation during endoscopic peritoneoscopy causes wide variations in intra-abdominal pressure. Its effects on splanchnic microcirculation may differ from those of steady intra-abdominal pressure, because pressure characteristics affect crucial intravascular hemodynamic forces- pressure and shear--adapting flow to local metabolic needs. Our aim was to assess the effect of natural orifice transluminal endoscopic surgery (NOTES) peritoneoscopy on splanchnic microcirculatory blood flow. METHODS: Twenty-one swine were randomized to the following: cholecystectomy by transgastric NOTES (n = 8), cholecystectomy by standard laparoscopy (Lap) (n = 8), and a sham group (n = 5). During NOTES, CO2 was manually insufflated with a maximum allowed pressure of 30 mm Hg. In the Lap group, intra-abdominal pressure was maintained at 14 mm Hg. Systemic hemodynamics were measured, and microcirculatory blood flow was quantified by using colored microspheres. RESULTS: Mean intra-abdominal pressure was lower in NOTES than in the Lap group (P = .038). In both groups, cardiac index and preload remained unchanged, whereas systemic vascular resistances increased over time, with a lesser increase in the Lap group (2-way analysis of variance; P = .041). In pneumoperitoneum groups, microcirculatory blood flow decreased similarly in the renal medulla, stomach, small bowel, colon, and mesocolon by 30%, 45%, 34%, 32%, and 37%, respectively. In NOTES, there was a greater microcirculatory blood flow decrease in the renal cortex (NOTES 41% vs Lap 35%; P = .044) and mesentery (NOTES 44% vs Lap 38%; P = .041). CONCLUSIONS: These findings suggest that both types of pneumoperitoneum have similar physiologic effects on microcirculatory blood flow. However, on-demand pneumoperitoneum (NOTES group) caused a greater microcirculatory blood flow decrease in areas with low metabolic needs, redistributing blood flow toward metabolically active areas. PMID- 26272860 TI - A glimpse of fear: Fast detection of threatening targets in visual search with brief stimulus durations. AB - Reliable detection of a threat based on temporally restricted information allows organisms to activate their defensive mechanisms. In the present study we investigated attentional efficiency for prototypical evolutionarily relevant stimuli, snakes (compared with spiders and mushrooms), during visual search conditions in which displays were presented for brief durations and under conditions of high perceptual load. Participants were exposed to a visual search paradigm in which the duration of the display varied between 150 and 300 ms. Perceptual load was manipulated using small, medium, and larger displays (4, 6, and 8 items, respectively). The results showed that fear stimuli, compared with neutral stimuli, were more accurately and quickly detected under both visually degraded conditions. The results also showed differences between the two categories of fear-relevant stimuli (snakes and spiders) in their dependency on perceptual load manipulations. Snake targets were overall detected more accurately than spiders, with this snake advantage effect being more clear-cut with many distracters (high load) than with few (low load). The results were interpreted in light of an evolutionary-based theory (the snake detection theory), which posits that snakes are the prototypical predators of primates. PMID- 26272861 TI - Peer-comparison overconfidence: Does it measure bias in self-evaluation? AB - Overconfidence is generally regarded as one of the most robust findings in the psychology of judgment. A precise method for evaluating overconfidence is essential if researchers are to validate these findings. Although peer-comparison questions are a convenient tool for measuring overconfidence, their validity has been questioned. We employed a specific paradigm to verify the validity, and the respondents were asked to predict a verifiable future event in a real-world setting that allowed empirical checking and comparison between the actual result and the prediction. Studies 1 and 2 found that the actual percentile of overconfidence could be accurately predicted using our initial calculation of participants' peer-comparison overconfidence in answering questions about academic performance. Study 3 found a similar effect when using questions related to job hunting. All studies indicated that peer-comparison questions are valid for measuring bias in self-evaluation. Thus, future studies could employ peer comparison questions to investigate the domain specificity versus the domain generality of overconfidence. PMID- 26272862 TI - Intergenerational transmission of educational attainment: Three levels of parent child communication as mediators. AB - Although the intergenerational transmission of educational attainment has been confirmed by many researchers, its mechanism still remains controversial. Parent child communication has been regarded as one of the important mediators. The present study primarily aimed to examine the potentially mediating role of parent child communication in the transmission of educational attainment, based on a sample of 366 Chinese fifth and sixth graders. Parent-child communication was measured against the three levels of the parents' communication ability, the quality of the father-child and mother-child communications, and the relation between the two dyadic communications. The results duplicated the positive effect of parents' educational attainment on children's academic achievement. Moreover, it was found that parents' communication ability alone played a mediating role, and that the three levels of parent-child communication constructed a "mediator chain" between the parents' educational attainment and the children's academic achievement. Finally, the intergenerational transmission of educational attainment in China and the mediating role of the three levels of parent-child communication were discussed. PMID- 26272863 TI - The impact of creative tendency, academic performance, and self-concept on creative science problem-finding. AB - This study was designed to address the impacts of science performance, science self-concept, and creative tendency on the creative science problem-finding (CSPF) ability of a sample of Chinese middle-school students. Structural equation modeling was used to indicate that CSPF could be directly predicted by creative tendency and academic performance, and indirectly predicted by science self concept. The findings strongly support the idea that curiosity, imagination, and domain-specific knowledge are important for CSPF, and science self-concept could be mediated by knowledge that affects CSPF. PMID- 26272864 TI - Impact of the aging process on event-, time-, and activity-based prospective memory. AB - The present study aimed to compare the impact of the aging process on event-, time-, and activity-based prospective memory (PM) and to explore the aging patterns of PM-related cognitive functions. Seventy-five participants were recruited and divided into three age groups: young (20-24 years old), young-old (60-70 years old), and older-old (greater than 70 years old). A computerized PM test and a set of tests capturing executive functions, retrospective memory, and working memory were administered to all participants. Significant age effects were only found for event-based PM and time-based PM. However, event-based PM was noted to decline gradually, whereas time-based PM was noted to deteriorate abruptly with age. For older, but not young participants, performance on the time based PM tasks was significantly improved under a more lenient scoring criterion which had an increased response time window. Measures of executive functions and retrospective memory were significantly associated with PM, but these relations disappeared after controlling for age and education. Working memory was found to be the most important contributor to the effect of age on PM. These findings suggest a differential aging process for event-, time-, and activity-based PM. PMID- 26272865 TI - Reply: To PMID 25446660. PMID- 26272867 TI - Left Atrial Volume Index Predicts Recurrence of Stroke in Patients with Nonsustained Atrial Tachycardia. AB - BACKGROUND: Nonsustained atrial tachycardia (NSAT) is known to appear more frequently in patients with paroxysmal atrial fibrillation (AF). Enlarged left atrium (LA) is considered to be an independent risk factor for newly diagnosed AF. METHODS: We investigated the risk factors for predicting the stroke recurrence in NSAT patients. In total, 252 patients (114 women, mean 70 +/- 11 years) with acute ischemic stroke and documented NSAT in 24-hour Holter monitoring were enrolled and followed. All patients underwent echo-Doppler evaluations. RESULTS: During a mean follow-up period of 35 +/- 31 months, the stroke recurrence rate was 11.1% (28 of 252). The patients with recurrence (n = 28) had higher left atrium volume index (LAVI, P < .001) and higher E/e' (P = .028) compared with those without recurrence (n = 224). On the Kaplan-Meier survival analysis, stroke recurrence rate was significantly higher in patients with enlarged LA (LAVI >28 mm3/m2; P < .001 by the log-rank test), and it remained significant in multivariate analysis (hazard ratio, 1.154; 95% confidence interval [CI], 1.099-1.212, P < .001). CONCLUSIONS: In patients with acute ischemic stroke and NSAT, enlarged LA predicts an increased risk of stroke recurrence. This study supports the necessity of prolonged rhythm monitoring in stroke patients with NSAT and enlarged LA to detect undiagnosed AF and consequently considering anticoagulation therapy. PMID- 26272866 TI - Solitomab, an EpCAM/CD3 bispecific antibody construct (BiTE), is highly active against primary uterine serous papillary carcinoma cell lines in vitro. AB - BACKGROUND: Uterine serous carcinoma is an aggressive form of endometrial cancer that carries an extremely poor prognosis. Solitomab is a novel bispecific single chain antibody construct that targets epithelial cell adhesion molecule on tumor cells and also contains a CD3 binding region. We evaluated the expression levels of epithelial cell adhesion molecule and the in vitro activity of solitomab against primary uterine serous carcinoma cell lines in vitro and ex-vivo in the ascites of patients with uterine serous carcinoma. OBJECTIVE: The purpose of this study was to determine the frequency of expression of epithelial cell adhesion molecule on uterine serous carcinoma cell lines and the ability of solitomab to modulate immune responses (T-cell proliferation, activation, cytokine production, and tumor killing) to tumor cells when it is combined with lymphocytes and epithelial cell adhesion molecule-positive cell lines or epithelial cell adhesion molecule-positive ascitic fluid in vitro. STUDY DESIGN: Epithelial cell adhesion molecule expression was evaluated by flow cytometry in a total of 14 primary uterine serous carcinoma cell lines. Sensitivity to solitomab-dependent cellular cytotoxicity was tested against a panel of primary uterine serous carcinoma cell lines that express different levels of epithelial cell adhesion molecule in standard 4-hour chromium release assays. The proliferative activity, activation, cytokine secretion (ie, type I vs type II), and cytotoxicity of solitomab in autologous tumor-associated T cells in the ascitic fluid of patients with uterine serous carcinoma was also evaluated by carboxyfluorescein succinimidyl ester and flow-cytometry assays. Differences in epithelial cell adhesion molecule expression, solitomab-dependent cellular-cytotoxicity levels were analyzed with the use of an unpaired t test. T-cell activation marker increase and cytokine release were analyzed by a paired t test. RESULTS: Surface expression of epithelial cell adhesion molecule was found in 85.7% (12 of 14) of the uterine serous carcinoma cell lines that were tested by flow cytometry. Epithelial cell adhesion molecule-positive cell lines were found resistant to natural killer cells or T-cell-mediated killing after exposure to peripheral blood lymphocytes in 4-hour chromium-release assays (mean killing +/- standard of the mean, 2.7% +/ 3.1% after incubation of epithelial cell adhesion molecule-positive cell lines with control bispecific antibody construct). In contrast, after incubation with solitomab, epithelial cell adhesion molecule-positive uterine serous carcinoma cells became highly sensitive to T-cell cytotoxicity (mean killing, 25.7% +/- 4.5%; P < .0001) by peripheral blood lymphocytes. Ex vivo incubation of autologous tumor-associated lymphocytes with epithelial cell adhesion molecule that expressed malignant cells in ascites with solitomab resulted in a significant increase in T-cell proliferation in both CD4+ and CD8+ T cells, increase in T-cell activation markers (ie, CD25 and HLA-DR), and a reduction in number of viable uterine serous carcinoma cells in ascites (P < .001). CONCLUSION: Solitomab induces robust immunologic responses in vitro that result in increased T-cell activation, proliferation, production of cytokines, and direct killing of tumor cells. These findings suggest that solitomab may represent a novel, potentially effective agent for the treatment of recurrent/metastatic and/or chemo-resistant uterine serous carcinoma overexpressing epithelial cell adhesion molecule. PMID- 26272868 TI - Antiplatelet Drug Use and Cerebral Microbleeds: A Meta-analysis of Published Studies. AB - BACKGROUND: Antiplatelet therapy is a potential risk factor for intracerebral hemorrhage, and cerebral microbleeds reflect small perivascular hemorrhages without clinical symptoms. The question regarding whether antiplatelet therapy increases the risk of cerebral microbleeds has not yet reached a consensus. METHODS: We conducted a search in English database and extracted data from studies assessing the relationship between antiplatelet therapy and cerebral microbleeds. Then, we adopted the Review Manager 5.2 package to calculate pooled odds ratios (ORs) with the method of the inverse variance. RESULTS: We pooled data from 11 studies involving 10429 participants. The results revealed that there was a significant association between antiplatelet therapy and cerebral microbleeds in hemorrhagic stroke patients (OR, 1.96; 95% confidence interval [CI], 1.22-3.16) and ischemic stroke patients (OR, 1.65; 95% CI, 1.06-2.59), but not stroke-free population (OR, 1.30; 95% CI, .96-1.74). When stratified by population ethnicity, the association between antiplatelet therapy and cerebral microbleeds was significant in hemorrhagic stroke (OR, 2.26; 95% CI, 1.25-4.08) and ischemic stroke (OR, 2.18; 95% CI, 1.02-4.67) patients from Asian countries, but not significant in hemorrhagic stroke (OR, 1.95; 95% CI, .33-11.37) and ischemic stroke (OR, 1.16; 95% CI, .87-1.54) patients from European countries. CONCLUSIONS: Antiplatelet therapy may increase the risk of cerebral microbleeds in stroke population. In addition, the relationship between antiplatelet therapy and cerebral microbleeds may be influenced by ethnic factors. More and larger prospective studies are urgently required to verify our results, because the studies to date are retrospective and the available data are limited. PMID- 26272869 TI - Photonic ququart logic assisted by the cavity-QED system. AB - Universal quantum logic gates are important elements for a quantum computer. In contrast to previous constructions of qubit systems, we investigate the possibility of ququart systems (four-dimensional states) dependent on two DOFs of photon systems. We propose some useful one-parameter four-dimensional quantum transformations for the construction of universal ququart logic gates. The interface between the spin of a photon and an electron spin confined in a quantum dot embedded in a microcavity is applied to build universal ququart logic gates on the photon system with two freedoms. Our elementary controlled-ququart gates cost no more than 8 CNOT gates in a qubit system, which is far less than the 104 CNOT gates required for a general four-qubit logic gate. The ququart logic is also used to generate useful hyperentanglements and hyperentanglement-assisted quantum error-correcting code, which may be available in modern physical technology. PMID- 26272870 TI - Synergistic Effect of Dual Electron-Cocatalysts for Enhanced Photocatalytic Activity: rGO as Electron-Transfer Mediator and Fe(III) as Oxygen-Reduction Active Site. AB - For a high-performance cocatalyst-modified photocatalyst, an effective interfacial separation of photogenerated electron from its corresponding holes and its following reduction reaction at the active sites are highly required. However, it is difficult for a single-component cocatalyst to simultaneously realize the crucial functions. In this study, an effective interfacial transfer of photogenerated electrons and its following rapid oxygen-reduction can be easily realized in a dual electron-cocatalyst modified Fe(III)/rGO-TiO2 photocatalyst, where the rGO nanosheets function as an electron-transfer mediator for the effective transfer of photogenerated electrons from the TiO2 surface while the Fe(III) cocatalyst serves as an electron-reduction active site to promote the following interfacial oxygen reduction. In this case, the rGO nanosheets were firstly loaded on the TiO2 nanoparticle surface by a hydrothermal method and then the Fe(III) cocatalyst was further modified on the rGO nanosheets by an impregnation method to prepare the Fe(III)/rGO-TiO2 photocatalyst. It was found that the dual electron-cocatalyst modified Fe(III)/rGO-TiO2 photocatalyst showed an obviously higher photocatalytic performance than the naked TiO2 and single-cocatalyst modified photocatalysts (such as Fe(III)/TiO2 and rGO-TiO2) owing to the synergistic effect of rGO and Fe(III) bi-cocatalysts. The present work can provide some new insights for the smart design of high-efficiency photocatalytic materials. PMID- 26272871 TI - Treating liver fat and serum triglyceride levels in NAFLD, effects of PNPLA3 and TM6SF2 genotypes: Results from the WELCOME trial. AB - BACKGROUND & AIMS: Genetic variation in both patatin-like phospholipase domain containing protein-3 (PNPLA3) (I148M) and the transmembrane 6 superfamily member 2 protein (TM6SF2) (E167K) influences severity of liver disease, and serum triglyceride concentrations in non-alcoholic fatty liver disease (NAFLD), but whether either genotype influences the responses to treatments is uncertain. METHODS: One hundred three patients with NAFLD were randomised to omega-3 fatty acids (DHA+EPA) or placebo for 15-18months in a double blind placebo controlled trial. Erythrocyte enrichment with DHA and EPA was measured by gas chromatography. PNPLA3 and TM6SF2 genotypes were measured by PCR technologies. Multivariable linear regression and analysis of covariance were undertaken to test the effect of genotypes on omega-3 fatty acid enrichment, end of study liver fat percentage and serum triglyceride concentrations. All models were adjusted for baseline measurements of each respective outcome. RESULTS: Fifty-five men and 40 women (Genotypes PNPLA3 I148M, 148I/I=41, 148I/M=43, 148M/M=11; TM6SF2 E167K 167E/E=78, 167E/K+167K/K=17 participants) (mean +/- SD age, 51 +/- 11 years) completed the trial. Adjusting for baseline measurement, measured covariates and confounders, PNPLA3 148M/M variant was independently associated with percentage of DHA enrichment (B coefficient -1.02 (95% CI -1.97, -0.07), p=0.036) but not percentage of EPA enrichment (B coefficient -0.31 (95% CI -1.38, 0.75), p=0.56). This genotype was also independently associated with end of study liver fat percentage (B coefficient 9.5 (95% CI 2.53, 16.39), p=0.008), but not end of study triglyceride concentration (B coefficient -0.11 (95% CI -0.64, 0.42), p=0.68). CONCLUSIONS: PNPLA3 148M/M variant influences the changes in liver fat and DHA tissue enrichment during the trial but not the change in serum triglyceride concentration. PMID- 26272872 TI - Upregulation of miR-125b by estrogen protects against non-alcoholic fatty liver in female mice. AB - BACKGROUND & AIMS: Due to the protective effect of estrogen against hepatic fat accumulation, the prevalence of non-alcoholic fatty liver disease (NAFLD) in premenopausal women is lower than that in men at the same age and in postmenopausal women. Our study was to further elucidate an underlying mechanism by which estrogen prevents NAFLD from miRNA perspective in female mice. METHODS: miRNA expression was evaluated by TaqMan miRNA assay. Luciferase and ChIP assay were done to validate regulation of miR-125b by estrogen via estrogen receptor alpha (ERalpha). Nile red and Oil red O staining were used to check lipid content. Overexpressing or inhibiting the physiological role of miR-125b in the liver of mice through injecting adenovirus were used to identify the function of miR-125b in vivo. RESULTS: miR-125b expression was activated by estrogen via ERalpha in vitro and in vivo. miR-125b inhibited lipid accumulation both in HepG2 cells and primary mouse hepatocytes. Consistently, ovariectomized or liver specific ERalpha knockdown mice treated with miR-125b overexpressing adenoviruses were resistant to hepatic steatosis induced by high-fat diet, due to decreased fatty acid uptake and synthesis and decreased triglyceride synthesis. Conversely, inhibiting the physiological role of miR-125b with a sponge decoy slightly promoted liver steatosis with a high-fat diet. Notably, we provided evidence showing that fatty acid synthase was a functional target of miR-125b. CONCLUSION: Our findings identify a novel mechanism by which estrogen protects against hepatic steatosis in female mice via upregulating miR-125b expression. PMID- 26272873 TI - The role of platelets in liver regeneration - What don't we know? PMID- 26272874 TI - Effects of elevated atmospheric CO2 concentrations, clipping regimen and differential day/night atmospheric warming on tissue nitrogen concentrations of a perennial pasture grass. AB - Forecasting the effects of climate change on nitrogen (N) cycling in pastures requires an understanding of changes in tissue N. We examined the effects of elevated atmospheric CO2 concentration, atmospheric warming and simulated grazing (clipping frequency) on aboveground and belowground tissue N concentrations and C : N ratios of a C3 pasture grass. Phalaris aquatica L. cv. 'Holdfast' was grown in the field in six transparent temperature gradient tunnels (18 * 1.5 * 1.5 m each), three at ambient atmospheric CO2 and three at 759 p.p.m. CO2. Within each tunnel, there were three air temperature treatments: ambient control, +2.2/+4.0 degrees C above ambient day/night warming and +3.0 degrees C continuous warming. A frequent and an infrequent clipping treatment were applied to each warming * CO2 combination. Green leaf N concentrations were decreased by elevated CO2 and increased by more frequent clipping. Both warming treatments increased leaf N concentrations under ambient CO2 concentrations, but did not significantly alter leaf N concentrations under elevated CO2 concentrations. Nitrogen resorption from leaves was decreased under elevated CO2 conditions as well as by more frequent clipping. Fine root N concentrations decreased strongly with increasing soil depth and were further decreased at the 10-60 cm soil depths by elevated CO2 concentrations. The interaction between the CO2 and warming treatments showed that leaf N concentration was affected in a non-additive manner. Changes in leaf C : N ratios were driven by changes in N concentration. Overall, the effects of CO2, warming and clipping treatments on aboveground tissue N concentrations were much greater than on belowground tissue. PMID- 26272880 TI - Do patients with a continuous-flow left ventricular assist device benefit from induced-pulsatility or are we just spinning our wheels? PMID- 26272875 TI - Specificity of Incident Diagnostic Outcomes in Patients at Clinical High Risk for Psychosis. AB - It is not well established whether the incident outcomes of the clinical high risk (CHR) syndrome for psychosis are diagnostically specific for psychosis or whether CHR patients also are at elevated risk for a variety of nonpsychotic disorders. We collected 2 samples (NAPLS-1, PREDICT) that contained CHR patients and a control group who responded to CHR recruitment efforts but did not meet CHR criteria on interview (help-seeking comparison patients [HSC]). Incident diagnostic outcomes were defined as the occurrence of a SIPS-defined psychosis or a structured interview diagnosis from 1 of 3 nonpsychotic Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) groups (anxiety, bipolar, or nonbipolar mood disorder), when no diagnosis in that group was present at baseline. Logistic regression revealed that the CHR vs HSC effect did not vary significantly across study for any emergent diagnostic outcome; data from the 2 studies were therefore combined. CHR (n = 271) vs HSC (n = 171) emergent outcomes were: psychosis 19.6% vs 1.8%, bipolar disorders 1.1% vs 1.2%, nonbipolar mood disorders 4.4% vs 5.3%, and anxiety disorders 5.2% vs 5.3%. The main effect of CHR vs HSC was statistically significant (OR = 13.8, 95% CI 4.2 45.0, df = 1, P < .001) for emergent psychosis but not for any emergent nonpsychotic disorder. Sensitivity analyses confirmed these findings. Within the CHR group emergent psychosis was significantly more likely than each nonpsychotic DSM-IV emergent disorder, and within the HSC group emergent psychosis was significantly less likely than most emergent nonpsychotic disorders. The CHR syndrome is specific as a marker for research on predictors and mechanisms of developing psychosis. PMID- 26272881 TI - [Evaluation of the quality control of anticoagulation in patients with atrial fibrillation in a Primary Health Care Area of Madrid]. AB - OBJECTIVE: To calculate the time in therapeutic range (TTR), as well as the scores on the CHADS2 scale in anticoagulated patients with non-valvular atrial fibrillation, attending the Primary Care Health Centre of Aravaca. LOCATION: Basic health area of Aravaca (Madrid). DESIGN: Retrospective observational study. PARTICIPANTS: The Community of Madrid provides a list of patients with non valvular atrial fibrillation and on anticoagulant therapy in the centre. Excluding those with less than 8 INRs, who began treatment after January 2011, interrupted by inter-current treatment or had cancer or coagulopathy. The study period is from 1 January 2012 to 1 January 2013. MAIN MEASUREMENTS: The TTR (fraction of INRs in range) was the primary endpoint. The score was also calculated on the CHADS2 scale. RESULTS: A value of 56.28% TTR (59.5-53.1) was obtained from a sample of 963 INRs. Just over half (52%) of patients had a TTR<60%. There were 65 patients with a mean age of 80+/-7.5 years. The distribution of risk factors for the CHADS2 scale was: Heart failure 18.5%; hypertension 80%; diabetes 29.2%, and embolic events 18.5%. CONCLUSION: The results of our sample TTR is suboptimal (<60%), which implies an increased risk for embolic episodes and increased likelihood of bleeding. We need to incorporate into our clinical practice an objective measure of the quality of anticoagulation in order to identify poorly controlled patients and introduce corrective measures. PMID- 26272884 TI - Health Education Specialists' Knowledge, Attitudes, and Perceptions of the Patient Protection and Affordable Care Act. AB - The changing landscape of health care as a result of the Patient Protection and Affordable Care Act (ACA) may provide new opportunities for health education specialists (HES). The purpose of this study was to survey HES in the United States on their knowledge and attitudes of the ACA and assess their perceptions of job growth under the law. A random sample of 220 (36% response rate) certified HES completed a 53-item cross sectional survey administered online through Qualtrics. Findings were compared to public opinion on health care reform. HES are highly favorable of the law (70%) compared to the general public (23%). A total of 85% of respondents were able to list a provision of the ACA, and most (81%) thought the ACA would be successful at increasing insured Americans. Over half (64.6%) believe job opportunities will increase. Those who viewed the law favorably were significantly more likely to score better on a knowledge scale related to the ACA. HES understand publicized provisions but are uncertain about common myths and specific provisions related to Title IV, "Prevention of Chronic Disease and Improving Public Health." Directed and continuing education to HES regarding the ACA is warranted. PMID- 26272885 TI - Dietary Adjuncts for Improving Testosterone Levels in Hypogonadal Males. AB - An increasing number of men are being diagnosed with hypogonadism. While many benefit from testosterone supplementation therapy, others who do not meet the criteria for hormone supplementation have turned to dietary adjuncts as a way or gaining improvements in libido, energy, and physical performance. These oral adjunct medications include controlled substances such as androstenedione, androstenediol as well as other "over-the-counter" options like DHEA (dehydroepiandrosterone) and herbal remedies like Tribulus terrestris This review will focus on the use of these adjunct medications in isolation, or in combination with testosterone supplementation therapy as well as the biochemical nature of the supplements, the results of scientific trials as well as the side effects that limit their use. At the end of this review, physicians will have an improved understanding of the popular testosterone adjuncts being used currently as well as the availability of these substances and how they are used. PMID- 26272886 TI - Factor Structure of the Gotland Scale of Male Depression in Two Samples of Men With Prostate Cancer: Implications for Treating Male Depression. AB - Up to a quarter of all prostate cancer (PCa) patients suffer from clinically significant depression but treatments are inconsistent and short-lived in their efficacy. One possible reason could be that "male depression" is not adequately diagnosed by the criteria for major depressive disorder (MDD) used in many clinical settings. In response to this limitation, the Gotland Scale of Male Depression (GSMD) was developed to identify the extra symptoms of MDD in men. Although the factor structure of the GSMD has been reported in non-PCa samples, it has not been determined for this group of men. Two samples of PCa patients were recruited, 191 from Australia and 138 from the United Kingdom and all patients received the GSMD individually, plus a background questionnaire. Two factor solutions were identified for each of the two samples. The Australian sample was characterized by changes in emotional and somatic function, followed by depressed mood. The U.K. sample exhibited the same two-factor solution but in reverse order of weighting. Targeted treatments for depression in PCa patients may benefit from identification of the loadings that individual patients have on these two GSMD factors so that specific clinical profiles and treatment needs may be based on this information about their depression. PMID- 26272887 TI - Patient Decision Making Prior to Radical Prostatectomy: What Is and Is Not Involved. AB - The current study assessed the decision-making process before surgery in prostate cancer patients. A structured telephone interview was conducted by an independent third party in 162 consecutive patients who underwent surgery for prostate cancer. Responders revealed that details regarding diagnosis and treatment alternatives were withheld from a significant number of patients. Radiation and active surveillance were presented as alternative options to surgery in 57 (39%) and 20 (14%) of responders, respectively. Twenty-six (18%) patients reported not being informed regarding potential surgical side effects. Patients were not active participants in critical aspects of decision making in 61 (42%) of the cases. Being inadequately informed and more frequent visits to the urologist appeared to make decisions more difficult. Treatment regret was reported by 23 (16%) of the patients who underwent surgery and was more common when the patient was not involved in the decision or was inadequately informed. As such, shared decision making should replace paternalism when managing patients with localized prostate cancer in urologic practice. PMID- 26272883 TI - Natural Variation of Plant Metabolism: Genetic Mechanisms, Interpretive Caveats, and Evolutionary and Mechanistic Insights. AB - Combining quantitative genetics studies with metabolomics/metabolic profiling platforms, genomics, and transcriptomics is creating significant progress in identifying the causal genes controlling natural variation in metabolite accumulations and profiles. In this review, we discuss key mechanistic and evolutionary insights that are arising from these studies. This includes the potential role of transport and other processes in leading to a separation of the site of mechanistic causation and metabolic consequence. A reilluminated observation is the potential for genomic variation in the organelle to alter phenotypic variation alone and in epistatic interaction with the nuclear genetic variation. These studies are also highlighting new aspects of metabolic pleiotropy both in terms of the breadth of loci altering metabolic variation as well as the potential for broader effects on plant defense regulation of the metabolic variation than has previously been predicted. We also illustrate caveats that can be overlooked when translating quantitative genetics descriptors such as heritability and per-locus r(2) to mechanistic or evolutionary interpretations. PMID- 26272889 TI - Comparison of bivalirudin to lepirudin and argatroban in patients with heparin induced thrombocytopenia. AB - OBJECTIVE: To evaluate the safety, effectiveness, and dosing of off-label bivalirudin to argatroban and lepirudin in patients with heparin-induced thrombocytopenia (HIT) using a new pharmacist driven protocol. METHODS: Retrospective cohort study of forty eight patients treated with lepirudin, argatroban, or bivalirudin from November 2010 to February 2012 for suspected HIT. Patients were excluded if the bivalirudin therapy was being used for acute coronary syndrome or if the treatment duration was less than 24 hours. The primary endpoint was time to therapeutic activated partial thromboplastin time (aPTT 50-90 seconds for argatroban and bivalirudin and 50-85 seconds for lepirudin). The secondary endpoints were elevation in international normalized ratio (INR), bleeding episodes, and percent time in aPTT target range. RESULTS: Patients receiving bivalirudin reached a therapeutic aPTT more quickly than those receiving argatroban and lepirudin (3.7 hours vs. 14.2 hours vs. 14.7 hours, p <0.001). The INR was increased more in patients treated with argatroban than lepirudin and bivalirudin (1.3 vs. 0.3 vs. 0.4, p = 0.4). Clinically significant bleeding in patients treated with bivalirudin was significantly lower than that observed with argatroban or lepirudin (7% vs. 22% vs. 56%, p = 0.02). The average percentage of therapeutic aPTTs drawn was higher for patients treated with bivalirudin than those patients treated with argatroban and lepirudin (90% vs. 66% vs. 67%, p = 0.2). CONCLUSION: A pharmacist-driven protocol for bivalirudin provided a significantly shorter time to therapeutic aPTT and lower bleeding rate for patients being treated for HIT when compared to lepirudin and argatroban. A larger study should be considered to confirm the results of this single center study. PMID- 26272890 TI - Evaluation of pharmacy services in emergency departments of Veterans Affairs Medical Centers. AB - OBJECTIVE: In 2008, the American Society of Health-System Pharmacists (ASHP) published a national survey that revealed only 6.8% of hospitals surveyed had a pharmacist assigned to the emergency department (ED) for any period of time. This survey was distributed among general and children's medical-surgical hospitals in the United States and did not include any Veterans Affairs (VA) Medical Centers. To date, there have been no identified survey studies describing the prevalence of pharmacy services within VA EDs. The objectives of this study are to determine the prevalence of dedicated pharmacy services within VA EDs, categorize the types of pharmacy services, determine if interventions/outcomes related to pharmacy services were collected, and assess the desire for pharmacy services in facilities that did not currently have dedicated pharmacy services. METHODS: The study was designed as a cross-sectional survey study conducted between January 14, 2010 and March 29, 2010. The study population included Pharmacy Clinical Coordinators employed at a VA facility. An initial email containing a link to the web-based survey was distributed via the national Pharmacy Clinical Coordinator listserv. Results of the survey were analyzed using descriptive statistics. RESULTS: The survey was distributed to 153 VA Medical Centers and a total of 33 (21.6%) responses were received. Of the responses, 24 facilities (72.7%) documented the presence of an ED, and of those, 5 (20.8%) indicated that they had a pharmacist dedicated to providing pharmacy services to the ED. The most common pharmacy services provided included medication reconciliation, patient education/ counseling, pharmacotherapy recommendations, ED staff education, precepting activities, adverse drug reaction (ADR) reporting, and ensuring formulary compliance. Three of the 5 facilities documented interventions, with 1 facility documenting ADRs prevented and cost avoidance in addition to interventions. Of the 19 facilities that did not have a pharmacist dedicated to the ED, 16 (84.2%) indicated a desire for such services. CONCLUSION: A greater prevalence of ED pharmacy services was reported in VA facilities compared with a national sample of non-VA facilities. Despite the high prevalence and variety of dedicated pharmacy services provided to the ED, documentation of these services remains an area in need of improvement. PMID- 26272891 TI - Frequency and characteristics of hospital-sponsored pertussis revaccination programs in the southern United States. AB - OBJECTIVE: The Centers for Disease Control and Prevention (CDC) released guidelines in December, 2006, recommending revaccination against Bordetella pertussis with Tdap for all post-partum women and healthcare workers. The CDC recommendations specifically state "the postpartum Tdap should be administered before discharge from the hospital or birthing center" and "hospitals and ambulatory-care facilities should provide Tdap for healthcare personnel." The purpose of this survey was to determine the frequency and characteristics of hospital-sponsored pertussis revaccination programs in the southern United States. METHODS: A twenty-six question electronic survey was sent to a representative of either the infection control or pharmacy department of hospitals in the following south central states: Kentucky, Tennessee, Alabama, Mississippi, Arkansas, Louisiana, Oklahoma, and Texas. The survey was designed to collect information regarding the institution's demographic factors and Tdap vaccination policies. RESULTS: Thirty-seven of 120 surveys (30.8%) were returned. Thirty respondents (81.1%) reported awareness of the 2006 CDC recommendations. Of the 29 institutions offering labor and delivery services, 14 (48.3%) confirmed having a post-partum vaccination policy, 12 (41.4%) reported having no post partum vaccination policy, and 3 (10.3%) were unaware of whether a policy was currently in place. Of the 37 responding institutions, 34 (91.9%) offer employee vaccinations, although only 31 of those 34 programs (91.1%) offer Tdap to employees. CONCLUSION: According to survey responses, many institutions have not yet implemented Tdap vaccination programs for post-partum patients or healthcare workers according to CDC recommendations. There was no correlation between institution demographics and the presence or characteristics of Tdap revaccination programs. PMID- 26272892 TI - Reducing errors through discharge medication reconciliation by pharmacy services. AB - OBJECTIVE: Adverse drug events are an important cause of admissions to hospitals. Discrepancies in admission and discharge medications can contribute significantly to these adverse events. Patients are at risk of discrepancies in medications any time they experience a transition of care. Medication discrepancies occur more commonly when patients are discharged. Prevention of errors by undergoing medication reconciliation with review by a pharmacist can help avoid medication discrepancy-related errors. The objective of this study was to determine whether integration of pharmacist review in the process of medication reconciliation at discharge identifies and corrects discrepancies. METHODS: In the study population of internal medicine patients cared for by hospitalist physicians, we prospectively collected data from medication lists via chart review and patient interview and identified, using a pharmacist, any medication discrepancies. We then counted the number of discrepancies for each patient and categorized them by severity of potential adverse effect to the patient. RESULTS: There were 63 medication discrepancies in 104 included patients found by pharmacist's review and 41% (43) of patients had at least one medication discrepancy. Patients with 8 or more discharge medications were found to be at an increased risk of discrepancy (OR 8.5, p <0.001, 95% CI 2.8,25.5). Most discrepancies were considered minimal risk, 44.4% (28/63), or moderate risk, 49.2% (20/63) for adverse effect. CONCLUSION: About 2 out of 5 patients on the hospitalist service studied have discrepancies in their medications at discharge that can be identified and corrected by pharmacist intervention. Inclusion of pharmacists could improve the process by correcting these discrepancies to help avoid preventable adverse drug events. PMID- 26272882 TI - Boosting vaccine efficacy the natural (killer) way. AB - Coordination of the innate and adaptive immune systems is paramount to the development of protective humoral and cellular immunity following vaccination. Natural killer (NK) cells are front-line soldiers of the innate immune system, and recent studies have revealed functions for NK cells in long-lived immune memory and the regulation of adaptive immune responses. These findings suggest that NK cells may play important roles in the development of efficacious vaccines, as well as, in some contexts, failed immunizations. Here, we review the current understanding of the immunomodulatory and memory differentiation capabilities of NK cells. We examine the context dependency of the mechanisms and the nature of NK cell-mediated modulation of the immune response, and discuss how these insights may impact immunization strategies and the development of next generation vaccines. PMID- 26272893 TI - Development and implementation of a writing program to improve resident authorship rates. AB - PURPOSE: The development, implementation, and evaluation of a writing program with a formalized writing project as a component of postgraduate year 1 (PGY1) and postgraduate year 2 (PGY2) pharmacy residencies are described. SUMMARY: The writing program at Georgia Regents Medical Center/University of Georgia College of Pharmacy, a collaborative and jointly funded program, was initiated in the 2010-11 residency year. The goals of the program are to teach residents to communicate effectively, apply leadership skills, employ project management skills, and provide medication- and practice- related education and training. The program combines both writing experiences and mentorship. At the beginning of the residency year, trainees are presented with opportunities to participate in both research projects and writing projects. Specifically, opportunities within the writing program include involvement in review articles, case reports, drug information rounds, book chapters, letters to the editor, and high-quality medication-use evaluations for potential publication. The writing project is highly encouraged, and completion of a manuscript to be submitted for publication is expected by graduation. Nine papers were published by 8 of 18 PGY1 and PGY2 residents in the four years before program implementation. A total of 23 publications were published by 18 (72%) of the 25 PGY1 and PGY2 residents in the four years after implementation of the writing program. CONCLUSION: Implementation of a formal writing program increased the overall publication rate of residents. PMID- 26272888 TI - Racial Disparities in Sugar-Sweetened Beverage Consumption Change Efficacy Among Male First-Year College Students. AB - Racial disparities in weight-related outcomes among males may be linked to differences in behavioral change efficacy; however, few studies have pursued this line of inquiry. The purpose of this study was to determine the degree to which self-efficacy associated with changing sugar-sweetened beverage (SSB) consumption intake varies by race among male first-year college students. A self administered, cross-sectional survey was completed by a subsample of freshmen males (N = 203) at a medium-sized southern university. Key variables of interest were SSB intake and self-efficacy in reducing consumption of sugared beverages. African American and Whites had similar patterns of SSB intake (10.2 +/- 2.8 vs. 10.1 +/- 2.6); however, African Americans had lower proportions of individuals who were sure they could substitute sugared beverages with water (42.2% vs. 57.5%, p < .03). The results from logistic regression models suggest that self efficacy to reduce SSB intake among males vary by race. African American males were less likely to assert confidence in their ability to change behaviors associated with SSB (odds ratio = 0.51; confidence interval [0.27, 0.95]) in the full model adjusting for weight-related variables including SSB consumption. The findings suggest that weight loss and weight prevention interventions targeting young African American males require components that can elevate self-efficacy of this group to facilitate behavioral modifications that reduce SSB consumption and their risk for obesity-related diseases. PMID- 26272894 TI - Identifying opportunities to improve medication management in transitions of care. AB - PURPOSE: The types and causes of medication discrepancies during the transition from inpatient to ambulatory care were investigated. METHODS: A descriptive study was conducted at an academic outpatient group practice affiliated with a private nonacademic hospital to (1) describe discrepancies between inpatient discharge summaries and patient-reported medication lists, (2) identify patient and system factors related to breakdowns in medication documentation, and (3) determine reasons for medication discrepancies. During a four-month period, 17 patients at high risk for medication misadventures while transitioning from hospital care to outpatient follow-up were contacted by telephone soon after discharge and asked to provide information on all medications they were taking. Patient-reported medication lists were compared with the corresponding discharge summaries, and medication discrepancies were categorized by patient- and system-level factors using a validated instrument. RESULTS: Of the total of 96 discrepancies identified, more than two thirds (n = 67, 68%) involved the omission of a prescribed medication from either the patient-reported list or the discharge summary. Cardiovascular medications, including antihypertensives, antilipemics, diuretics, and antiarrhythmics, accounted for almost one quarter of all medication discrepancies. About 15% (n = 14) and 16% (n = 15) of identified discrepancies related to medication dose and frequency, respectively. CONCLUSION: Among 17 patients transitioning from inpatient to outpatient care, nearly 100 discrepancies between patient-reported medication lists and discharge summaries were identified. Most discrepancies were attributed to nonintentional nonadherence and resumption of home medications without instructions to do so. All 17 patients had at least 1 medication discrepancy categorized as involving a system-level factor. PMID- 26272896 TI - Conversion from thrice- to twice-daily pregabalin dosing for pain: Economic and clinical outcomes in a veteran population. AB - PURPOSE: Results of a study analyzing economic and clinical outcomes one year after conversion from thrice- to twice-daily pregabalin dosing for pain are presented. METHODS: A retrospective chart review was conducted at two Veterans Affairs facilities. The analyzed population included all patients receiving pregabalin for pain whose dosing was converted from thrice- to twice-daily pregabalin dosing during a one-year period. The primary endpoint was the economic impact of the conversion. Secondary endpoints included reversion to thrice-daily pregabalin dosing, pregabalin discontinuation, addition of medications for pain, and unscheduled neuropathy-related visits. RESULTS: Among the 57 patients included in the data analysis, 41 continued to take pregabalin twice daily, 10 had pregabalin discontinued, and 6 had dosing reverted to thrice daily. The mean age of patients and the distribution of add-on pain medications did not differ significantly between patients whose pregabalin dosing frequency remained at twice daily and patients whose frequency reverted to thrice daily. The costs associated with pregabalin therapy differed significantly between the preconversion and postconversion periods. A savings of $115,867 was realized from this conversion for both facilities combined over the course of one year. CONCLUSION: In patients receiving pregabalin for pain, conversion from thrice- to twice-daily pregabalin dosing-while maintaining the same daily dose-resulted in substantial cost savings while having little effect on clinical outcomes. PMID- 26272897 TI - Quality-improvement initiatives focused on enhancing customer service in the outpatient pharmacy. AB - PURPOSE: The development and implementation of quality-improvement initiatives to enhance customer service in an outpatient pharmacy of a Veterans Affairs (VA) medical center are described. SUMMARY: Historically low customer service satisfaction rates with the outpatient pharmacy at the Philadelphia Veterans Affairs Medical Center prompted this quality-improvement project. A three question survey was designed to be easily and quickly administered to veterans in the outpatient pharmacy waiting area. Using 5-point Likert scale, veterans were asked to rate (1) their overall experience with the outpatient pharmacy service and (2) their satisfaction with the customer service provided by the pharmacy department. They were also asked how they thought the pharmacy department could improve its customer service. After receiving feedback from the survey, several quality-improvement initiatives were developed. The initiatives were categorized as environmental, personnel, communicative, and technological. For each initiative, one or more tasks were developed and the initiatives were subsequently implemented over eight months. After each task was completed, veterans were surveyed to measure the impact of the change. A total of 79 veterans were surveyed before the implementation of the quality-improvement initiatives, and 49% and 68% rated their experience with the outpatient pharmacy and customer service favorably, respectively. Twenty-five veterans were surveyed after the implementation of numerous quality-improvement interventions, with 44% and 72% rating their experience with the outpatient pharmacy and customer service favorably. CONCLUSION: Customer service satisfaction with an outpatient pharmacy service at a VA medical center was enhanced through the implementation of various quality-improvement initiatives. PMID- 26272895 TI - Screening for diabetes in patients receiving second-generation atypical antipsychotics. AB - PURPOSE: Results of a study to assess adherence with a consensus statement for diabetes screening in patients receiving atypical antipsychotics and to evaluate the role of pharmacists in a patient-centered medical home in improving guideline adherence are presented. SUMMARY: For patients prescribed atypical antipsychotics, records were reviewed for glycosylated hemoglobin (HbA1c) testing within the past 12 months. If no HbA1c results were found within that time frame, physicians were sent an alert in the patient's electronic medical record requesting an HbA1c order. Patient medical records were reviewed to analyze the number of HbA1c orders before and after pharmacist intervention. Prior to pharmacist intervention, 17 of 120 (14%) patients were screened with HbA1c. As a result of pharmacist intervention, 86 alerts were sent to physicians to order an HbA1c level, 24 (28%) of which included an order for an HbA1c level. Eleven of 24 (46%) HbA1c test results were collected during study follow-up, and one prediabetic patient was identified. CONCLUSION: After pharmacist intervention, a greater number of patients receiving atypical antipsychotic medications had HbA1c levels monitored for evidence of type 2 diabetes. PMID- 26272898 TI - Implementation of a pharmacotherapy clinic into the patient centered medical home model by a second year pharmacy resident. AB - OBJECTIVE: Evaluate the impact a post graduate year 2 (PGY-2) pharmacy resident run clinic incorporated into the patient centered medical home (PCMH) model may have on achieving reduction in glycosylated hemoglobin (A1c), low density lipoprotein (LDL), and systolic and diastolic blood pressures (SBP and DBP) over six months in type 2 diabetics within the Veterans Health Administration (VHA). METHODS: This was a prospective, quasi-experimental study enrolling type 2 diabetics referred to the pharmacist-run clinic not meeting American Diabetes Association (ADA) treatment goals for A1c less than 7%, and/or LDL less than 100 mg/dL, and/or blood pressure (BP) less than 130/80 mmHg. Once signed informed consent was obtained, veterans were followed according to usual standards of care for six months with visits and lab follow-up at baseline, three, and six months (+/-45 days). The primary endpoint was the change in HbA1c, LDL, and BP from baseline to six months. Secondary endpoints included the change from baseline to three months in A1c, LDL, and BP and the percentage of patients who achieved ADA treatment goals for A1c, LDL, and BP at six months. RESULTS: Among the 24 patients included in the data analysis (100% male, 92% Caucasian), A1c decreased significantly from 7.56% to 7.19% (p = 0.0122) as well as LDL from 92.9 to 68.5 mg/dL (p = 0.0023), SBP from 131 to 124 mmHg (p = 0.0302), and DBP from 71.5 to 64.8 mmHg (p = 0.0012). The proportion of patients at recommended goal A1c <7% rose from 17% to 38%, as did the percentage of patients meeting ADA goals for LDL (75% to 96%), SBP (46% to 71%), and DBP (79% to 92%). CONCLUSION: Patients followed in a resident run pharmacotherapy clinic in the PCMH model with interventions over six months showed significant improvements in clinical endpoints including A1c, LDL, SBP, and DBP. PMID- 26272899 TI - Comparison of unfractionated heparin protocols using antifactor Xa monitoring or activated partial thrombin time monitoring. AB - OBJECTIVE: To determine whether there is a difference between an activated partial thromboplastin time (aPTT) based unfractionated heparin (UFH) protocol versus an antifactor Xa based UFH protocol with respect to 24-hour attainment of therapeutic levels. METHODS: This was an observational study performed at a 500 bed private, community hospital. The study included inpatients from January 2008 to December 2009 on our institution's aPTT UFH protocol and inpatients from July 2010 to March 2011 on our institution's antifactor Xa UFH protocol. The two groups were compared to determine whether a higher percentage of patients reached therapeutic goal within 24 hours of UFH initiation. Secondary outcomes evaluated the percentage of patients at therapeutic goal within 6 and 12 hours, incidence of bleeding, and number of UFH dosage adjustments within 24 hours between the two groups. RESULTS: One hundred twenty-one patients met inclusion criteria for this study; 79 in the aPTT group and 42 in the antifactor Xa group. At 24 hours, 74% of patients in the antifactor Xa group were at goal, versus 63% of patients in the aPTT group (p = 0.242). Nearly 57% of patients in the antifactor Xa group were at goal versus 27% in the aPTT group within 6 hours (p = 0.001). Subjects in the antifactor Xa group averaged 1.00 dosage adjustments per subject as compared to an 1.71 dosage adjustments per subject in the aPTT group within the first 24 hours (p = 0.003). CONCLUSION: The antifactor Xa assay should be used to monitor UFH versus aPTT due to less variability in measurements, the absence of a need for calibration with new reagents/coagulometers, quicker attainment of therapeutic levels, fewer dose adjustments, and similar bleeding rates. PMID- 26272900 TI - Comparing prasugrel to twice daily clopidogrel post percutaneous coronary intervention in a Veterans Affairs population. AB - OBJECTIVE: The purpose of this study was to compare various antiplatelet regimens in patients who experienced increased platelet reactivity on clopidogrel therapy with regards to cardiovascular outcomes, including need for revascularization, myocardial infarction (MI), stroke, and cardiovascular (CV) death. METHODS: A retrospective chart review was conducted on patients who received percutaneous coronary intervention (PCI) at the Richard L. Roudebush Veterans Affairs Medical Center and were subsequently prescribed either clopidogrel 75 mg twice daily, prasugrel 10 mg daily, or clopidogrel 75 mg daily with high platelet reactivity between October 1, 2009 and November 30, 2010. Correlations between antiplatelet regimens and prevention of cardiovascular outcomes and bleeding events were evaluated. Groups were evaluated statistically as two separate comparisons; the first comparison being clopidogrel twice daily versus prasugrel and the second comparison being clopidogrel twice daily versus clopidogrel daily in those patients with a P2Y12 test result of less than 50%. RESULTS: A total of 108 patients were included in the study. Eight events occurred in the clopidogrel twice daily group (n = 26), including five revascularizations and three MIs. Seven events occurred in the prasugrel group (n = 64), including two revascularizations, two MIs, two strokes, and one CV death. The difference between these groups was statistically significant (p = 0.031), with patients in the prasugrel group experiencing fewer events. Five events occurred in the clopidogrel daily group (n = 18), including one need for revascularization, two MIs, and two instances of CV death. There were no statistically significant differences in CV events between the clopidogrel twice daily group and clopidogrel daily group (p > 0.999). There were also no statistically significant differences in bleeding incidents for either of the comparisons; p > 0.999 and p = 0.676 respectively for the first and second comparisons. CONCLUSION: Patients on prasugrel had fewer cardiovascular events as compared to patients on clopidogrel twice daily with no difference in bleeding events. No difference was seen with regards to cardiovascular or bleeding events when comparing clopidogrel twice daily to clopidogrel daily in patients with increased platelet reactivity. Study results suggest that there is no benefit to dosing clopidogrel twice daily when compared to either prasugrel or once daily clopidogrel dosing. PMID- 26272902 TI - The Arabidopsis gene DIG6 encodes a large 60S subunit nuclear export GTPase 1 that is involved in ribosome biogenesis and affects multiple auxin-regulated development processes. AB - The circularly permuted GTPase large subunit GTPase 1 (LSG1) is involved in the maturation step of the 60S ribosome and is essential for cell viability in yeast. Here, an Arabidopsis mutant dig6 (drought inhibited growth of lateral roots) was isolated. The mutant exhibited multiple auxin-related phenotypes, which included reduced lateral root number, altered leaf veins, and shorter roots. Genetic mapping combined with next-generation DNA sequencing identified that the mutation occurred in AtLSG1-2. This gene was highly expressed in regions of auxin accumulation. Ribosome profiling revealed that a loss of function of AtLSG1-2 led to decreased levels of monosomes, further demonstrating its role in ribosome biogenesis. Quantitative proteomics showed that the expression of certain proteins involved in ribosome biogenesis was differentially regulated, indicating that ribosome biogenesis processes were impaired in the mutant. Further investigations showed that an AtLSG1-2 deficiency caused the alteration of auxin distribution, response, and transport in plants. It is concluded that AtLSG1-2 is integral to ribosome biogenesis, consequently affecting auxin homeostasis and plant development. PMID- 26272901 TI - Genome-wide mapping of 5-hydroxymethylcytosine in three rice cultivars reveals its preferential localization in transcriptionally silent transposable element genes. AB - 5-Hydroxymethylcytosine (5hmC), a modified form of cytosine that is considered the sixth nucleobase in DNA, has been detected in mammals and is believed to play an important role in gene regulation. In this study, 5hmC modification was detected in rice by employing a dot-blot assay, and its levels was further quantified in DNA from different rice tissues using liquid chromatography multistage mass spectrometry (LC-MS/MS/MS). The results showed large intertissue variation in 5hmC levels. The genome-wide profiles of 5hmC modification in three different rice cultivars were also obtained using a sensitive chemical labelling followed by a next-generation sequencing method. Thousands of 5hmC peaks were identified, and a comparison of the distributions of 5hmC among different rice cultivars revealed the specificity and conservation of 5hmC modification. The identified 5hmC peaks were significantly enriched in heterochromatin regions, and mainly located in transposable elements (TEs), especially around retrotransposons. The correlation analysis of 5hmC and gene expression data revealed a close association between 5hmC and silent TEs. These findings provide a resource for plant DNA 5hmC epigenetic studies and expand our knowledge of 5hmC modification. PMID- 26272903 TI - Photosynthetic lesions can trigger accelerated senescence in Arabidopsis thaliana. AB - Senescence is a highly regulated process characterized by the active breakdown of cells, which ultimately leads to the death of plant organs or whole plants. In annual plants such as Arabidopsis thaliana senescence can be observed in each individual leaf. Whether deficiencies in photosynthesis promote the induction of senescence was investigated by monitoring chlorophyll degradation, photosynthetic parameters, and reactive oxygen species accumulation in photosynthetic mutants. Several mutations affecting components of the photosynthetic apparatus, including psal-2, psan-2, and psbs, were found to lead to premature or faster senescence, as did simultaneous inactivation of the STN7 and STN8 kinases. Premature senescence is apparently not directly linked to an overall reduction in photosynthesis but to perturbations in specific aspects of the process. Dark induced senescence is accelerated in mutants affected in linear electron flow, especially psad2-1, psan-2, and pete2-1, as well as in stn7 and stn8 mutants and STN7 and STN8 overexpressor lines. Interestingly, no direct link with ROS production could be observed. PMID- 26272905 TI - TOPOLOGICAL MATTER. Observation of chiral currents at the magnetic domain boundary of a topological insulator. AB - A magnetic domain boundary on the surface of a three-dimensional topological insulator is predicted to host a chiral edge state, but direct demonstration is challenging. We used a scanning superconducting quantum interference device to show that current in a magnetized topological insulator heterostructure (EuS/Bi2Se3) flows at the edge when the Fermi level is gate-tuned to the surface band gap. We further induced micrometer-scale magnetic structures on the heterostructure and detected a chiral edge current at the magnetic domain boundary. The chirality of the current was determined by magnetization of the surrounding domain, and its magnitude by the local chemical potential rather than the applied current. Such magnetic structures provide a platform for detecting topological magnetoelectric effects and may enable progress in quantum information processing and spintronics. PMID- 26272904 TI - Discovery and spectroscopy of the young jovian planet 51 Eri b with the Gemini Planet Imager. AB - Directly detecting thermal emission from young extrasolar planets allows measurement of their atmospheric compositions and luminosities, which are influenced by their formation mechanisms. Using the Gemini Planet Imager, we discovered a planet orbiting the ~20-million-year-old star 51 Eridani at a projected separation of 13 astronomical units. Near-infrared observations show a spectrum with strong methane and water-vapor absorption. Modeling of the spectra and photometry yields a luminosity (normalized by the luminosity of the Sun) of 1.6 to 4.0 * 10(-6) and an effective temperature of 600 to 750 kelvin. For this age and luminosity, "hot-start" formation models indicate a mass twice that of Jupiter. This planet also has a sufficiently low luminosity to be consistent with the "cold-start" core-accretion process that may have formed Jupiter. PMID- 26272907 TI - Complete biosynthesis of opioids in yeast. AB - Opioids are the primary drugs used in Western medicine for pain management and palliative care. Farming of opium poppies remains the sole source of these essential medicines, despite diverse market demands and uncertainty in crop yields due to weather, climate change, and pests. We engineered yeast to produce the selected opioid compounds thebaine and hydrocodone starting from sugar. All work was conducted in a laboratory that is permitted and secured for work with controlled substances. We combined enzyme discovery, enzyme engineering, and pathway and strain optimization to realize full opiate biosynthesis in yeast. The resulting opioid biosynthesis strains required the expression of 21 (thebaine) and 23 (hydrocodone) enzyme activities from plants, mammals, bacteria, and yeast itself. This is a proof of principle, and major hurdles remain before optimization and scale-up could be achieved. Open discussions of options for governing this technology are also needed in order to responsibly realize alternative supplies for these medically relevant compounds. PMID- 26272908 TI - Broad-based molecular autopsy: a potential tool to investigate the involvement of subtle cardiac conditions in sudden unexpected death in infancy and early childhood. AB - OBJECTIVES: Sudden unexplained death in children is a tragic and traumatic event, often worsened when the cause of death cannot be determined. This work aimed to investigate the presence of putative pathogenic genetic variants in a broad spectrum of cardiomyopathy, channelopathy and aortic disease associated genes that may have increased these children's vulnerability to sudden cardiac death. DESIGN: We performed molecular autopsy of 41 cases of sudden unexplained death in infants and children through massive parallel sequencing of up to 86 sudden cardiac death-related genes. Multiple in silico analyses were conducted together with a thorough review of the literature in order to prioritise the putative pathogenic variants. RESULTS: A total of 63 variants in 35 cases were validated. The largest proportion of these variants is located within cardiomyopathy genes although this would have been more expected of channelopathy gene variants. Subtle microscopic features of heart tissue may indicate the presence of an early onset cardiomyopathy as a predisposing condition to sudden unexpected death in some individuals. CONCLUSIONS: Next-generation sequencing technologies reveal the existence of a wide spectrum of rare and novel genetic variants in sarcomere genes, compared with that of cardiac ion channels, in sudden unexplained death in infants and children. Our findings encourage further investigation of the role of early onset inherited cardiomyopathies and other diseases involving myocardial dysfunction in these deaths. Early detection of variants in these individuals could help to unmask subtle forms of disease within their relatives, who would eventually benefit from better counselling about their genetic history. PMID- 26272909 TI - Intrauterine versus extrauterine influences on adult disease risk: epidemiological aspects and sociocultural issues. PMID- 26272906 TI - MUCOSAL IMMUNOLOGY. Individual intestinal symbionts induce a distinct population of RORgamma+ regulatory T cells. AB - T regulatory cells that express the transcription factor Foxp3 (Foxp3(+) T(regs)) promote tissue homeostasis in several settings. We now report that symbiotic members of the human gut microbiota induce a distinct T(reg) population in the mouse colon, which constrains immuno-inflammatory responses. This induction-which we find to map to a broad, but specific, array of individual bacterial species requires the transcription factor Rorgamma, paradoxically, in that Rorgamma is thought to antagonize FoxP3 and to promote T helper 17 (T(H)17) cell differentiation. Rorgamma's transcriptional footprint differs in colonic T(regs) and T(H)17 cells and controls important effector molecules. Rorgamma, and the T(regs) that express it, contribute substantially to regulating colonic T(H)1/T(H)17 inflammation. Thus, the marked context-specificity of Rorgamma results in very different outcomes even in closely related cell types. PMID- 26272910 TI - Trends in admission and death rates due to paediatric head injury in England, 2000-2011. AB - BACKGROUND: The number of children admitted to hospital is increasing year on year, with very short-stay admissions doubling in the last decade. Childhood head injury accounts for half a million emergency department attendances in the UK every year. The National Institute for Health and Care Excellence (NICE) has issued three iterations of evidence-based national guidance for head injury since 2003. OBJECTIVES: To assess if any changes in the rates of admission, death or causes of head injury could be temporally associated with the introduction of sequential national guidelines by longitudinal analysis of the epidemiology of paediatric head injury admissions in England from 2000 to 2011. METHODS: Retrospective analysis of English Hospital Episode Statistics data of children under the age of 16 years old admitted to hospital with the discharge diagnosis of head injury. RESULTS: The number of hospital admissions with paediatric head injury in England rose by 10% from 34 150 in 2000 to 37 430 in 2011, with the proportion admitted for less than 1 day rising from 38% to 57%. The main cause of head injury was falls (42-47%). Deaths due to head injury decreased by 52% from 76 in 2000 to 40 in 2011. Road traffic accidents were the main cause of death in the year 2000 (67%) but fell to 40% by 2011. In 2000, children who were admitted or died from head injuries were more than twice as likely to come from the most deprived homes compared with least deprived homes. By 2011, the disparity for risk of admission had narrowed, but no change was seen for risk of death. CONCLUSIONS: Temporal relationships exist between implementation of NICE head injury guidance and increased admissions, shorter hospital stay and reduced mortality. The underlying cause of this association is likely to be multifactorial. PMID- 26272911 TI - Why do young children die in the UK? A comparison with Sweden. AB - BACKGROUND: The UK has a high child mortality rate, whereas Sweden's is lower (under-five mortality rates of five and three, respectively, in 2011).We therefore wished to compare causes of death in young children aged <5 years in the two countries. METHODS: Under-five mortality data were obtained from the Office of National Statistics for each of the individual countries within the UK for 3 years (2006-2008). Data for Sweden for the same period were obtained from the National Board of Health and Welfare. Causes of death were compared statistically using chi(2) test. RESULTS: There were a total of 14,104 and 1036 deaths aged <5 years in the UK and Sweden, respectively, between 2006 and 2008. The total numbers of live births during the same period were 2,295,964 and 315,884, respectively. The overall mortality rate in the UK was 614 per 100,000 children which was significantly higher than that in Sweden (328; p<0.001). The mortality rates for the three main causes of death in the UK (prematurity, congenital malformations and infections) were 138.5, 112.1 and 63.9, respectively, per 100,000 children. The mortality rates for the same three conditions in Sweden were 10.1, 88.6 and 34.8, respectively. They were all significantly more frequent in the UK than in Sweden (p<0.001), as were the majority of the disorders. Treatable infections, such as pneumonia, meningitis and septicaemia, in both neonates and young children had significantly higher mortality rates in the UK than in Sweden (p<0.001). CONCLUSIONS: In order to reduce the mortality rate in the UK, we need to try and reduce the causes of prematurity. Additionally, the care of children with treatable infections should be reviewed to understand ways in which to reduce the differences in mortality seen. PMID- 26272912 TI - Where do the differences in childhood mortality rates between England and Wales and Sweden originate? PMID- 26272913 TI - Pain and Prejudice: Does Collecting Information From the Standpoint of Exposed Workers Improve Scientific Examination of Work-Related Musculoskeletal Disorders? AB - The meaning, feasibility, and importance of scientific objectivity have been debated among public health scientists. The debate is particularly relevant to occupational health, because of frequent opposition between employer and worker interests. This article suggests that the concept of standpoint (J. Eakin) may be more useful than that of objectivity in framing discussion of work-related musculoskeletal disorders. Studies done from a "worker" standpoint can, for example, investigate and characterize environmental risk factors for work-related musculoskeletal disorders, while studies from an "employer" standpoint may concentrate on identifying individual workers likely to report work-related musculoskeletal disorders or those for whom consequences of work-related musculoskeletal disorders are more severe. Within "worker" standpoints, a distinction between "high-prestige worker" and "lower-prestige worker" standpoints can be identified in the current scientific debate about the health costs and benefits of prolonged standing vs prolonged sitting at work. Contact with workers, particularly lower-prestige workers, is critical to developing and sustaining a worker-based standpoint among researchers in occupational health. This contact can be facilitated by formal collaborations between universities and unions or other community groups. PMID- 26272914 TI - Do 'flexicurity' Policies Work for People With Low Education and Health Problems? A Comparison of Labour Market Policies and Employment Rates in Denmark, The Netherlands, Sweden, and the United Kingdom 1990-2010. AB - People with limiting longstanding illness and low education may experience problems in the labor market. Reduced employment protection that maintains economic security for the individual, known as "flexicurity," has been proposed as a way to increase overall employment. We compared the development of labor market policies and employment rates from 1990 to 2010 in Denmark and the Netherlands (representing flexicurity), the United Kingdom, and Sweden. Employment rates in all countries were much lower in the target group than for other groups over the study period. However, "flexicurity" as practiced in Denmark, far from being a "magic bullet," appeared to fail low-educated people with longstanding illness in particular. The Swedish policy, on the other hand, with higher employment protection and higher economic security, particularly earlier in the study period, led to higher employment rates in this group. Findings also revealed that economic security policies in all countries were eroding and shifting toward individual responsibility. Finally, results showed that active labor market policies need to be subcategorized to better understand which types are best suited for the target group. Increasing employment among the target group could reduce adverse health consequences and contribute to decreasing inequalities in health. PMID- 26272915 TI - Induction of lateral lumens through disruption of a monoleucine-based basolateral sorting motif in betacellulin. AB - Directed delivery of EGF receptor (EGFR) ligands to the apical or basolateral surface is a crucial regulatory step in the initiation of EGFR signaling in polarized epithelial cells. Herein, we show that the EGFR ligand betacellulin (BTC) is preferentially sorted to the basolateral surface of polarized MDCK cells. By using sequential truncations and site-directed mutagenesis within the BTC cytoplasmic domain, combined with selective cell-surface biotinylation and immunofluorescence, we have uncovered a monoleucine-based basolateral-sorting motif (EExxxL, specifically (156)EEMETL(161)). Disruption of this sorting motif led to equivalent apical and basolateral localization of BTC. Unlike other EGFR ligands, BTC mistrafficking induced formation of lateral lumens in polarized MDCK cells, and this process was significantly attenuated by inhibition of EGFR. Additionally, expression of a cancer-associated somatic BTC mutation (E156K) led to BTC mistrafficking and induced lateral lumens in MDCK cells. Overexpression of BTC, especially mistrafficking forms, increased the growth of MDCK cells. These results uncover a unique role for BTC mistrafficking in promoting epithelial reorganization. PMID- 26272916 TI - mRNA encoding Sec61beta, a tail-anchored protein, is localized on the endoplasmic reticulum. AB - Although one pathway for the post-translational targeting of tail-anchored proteins to the endoplasmic reticulum (ER) has been well defined, it is unclear whether additional pathways exist. Here, we provide evidence that a subset of mRNAs encoding tail-anchored proteins, including Sec61beta and nesprin-2, is partially localized to the surface of the ER in mammalian cells. In particular, Sec61b mRNA can be targeted to, and later maintained on, the ER using both translation-dependent and -independent mechanisms. Our data suggests that this process is independent of p180 (also known as RRBP1), a known mRNA receptor on the ER, and the transmembrane domain recognition complex (TRC) pathway components, TRC40 (also known as ASNA1) and BAT3 (also known as BAG6). In addition, our data indicates that Sec61b mRNA might access translocon-bound ribosomes. Our results show that certain tail-anchored proteins are likely to be synthesized directly on the ER, and this facilitates their membrane insertion. Thus, it is clear that mammalian cells utilize multiple mechanisms to ensure efficient targeting of tail-anchored proteins to the surface of the ER. PMID- 26272918 TI - MyoD transcription factor induces myogenesis by inhibiting Twist-1 through miR 206. AB - Twist-1 is mostly expressed during development and has been previously shown to control myogenesis. Because its regulation in muscle has not been fully exploited, the aim of this project was to identify micro (mi)RNAs in muscle that regulate Twist-1. miR-206, one of the most important muscle-specific miRNAs (myomiRs), was identified as a possible regulator of Twist-1 mRNA. Luciferase assays and transfections in human foetal myoblasts showed that Twist-1 is a direct target of miR-206 and that through this pathway muscle cell differentiation is promoted. We next investigated whether MyoD, a major myogenic transcription factor, regulates Twist-1 because it is known that MyoD induces expression of the miR-206 gene. We found that forced MyoD expression induced miR 206 upregulation and Twist-1 downregulation through binding to the miR-206 promoter, followed by increased muscle cell differentiation. Finally, experiments were performed in muscle cells from subjects with congenital myotonic dystrophy type 1, in which myoblasts fail to differentiate into myotubes. MyoD overexpression inhibited Twist-1 through miR-206 induction, which was followed by an increase in muscle cell differentiation. These results reveal a previously unidentified mechanism of myogenesis that might also play an important role in muscle disease. PMID- 26272919 TI - Genetic evidence for a microtubule-capture mechanism during polarised growth of Aspergillus nidulans. AB - The cellular switch from symmetry to polarity in eukaryotes depends on the microtubule (MT) and actin cytoskeletons. In fungi such as Schizosaccharomyces pombe or Aspergillus nidulans, the MT cytoskeleton determines the sites of actin polymerization through cortical cell-end marker proteins. Here we describe A. nidulans MT guidance protein A (MigA) as the first ortholog of the karyogamy protein Kar9 from Saccharomyces cerevisiae in filamentous fungi. A. nidulans MigA interacts with the cortical ApsA protein and is involved in spindle positioning during mitosis. MigA is also associated with septal and nuclear MT organizing centers (MTOCs). Super-resolution photoactivated localization microscopy (PALM) analyses revealed that MigA is recruited to assembling and retracting MT plus ends in an EbA-dependent manner. MigA is required for MT convergence in hyphal tips and plays a role in correct localization of the cell-end markers TeaA and TeaR. In addition, MigA interacts with a class-V myosin, suggesting that an active mechanism exists to capture MTs and to pull the ends along actin filaments. Hence, the organization of MTs and actin depend on each other, and positive feedback loops ensure robust polar growth. PMID- 26272917 TI - The NMDA receptor functions independently and as an LRP1 co-receptor to promote Schwann cell survival and migration. AB - NMDA receptors (NMDA-Rs) are ionotropic glutamate receptors, which associate with LDL-receptor-related protein-1 (LRP1) to trigger cell signaling in response to protein ligands in neurons. Here, we demonstrate for the first time that the NMDA R is expressed by rat Schwann cells and functions independently and with LRP1 to regulate Schwann cell physiology. The NR1 (encoded by GRIN1) and NR2b (encoded by GRIN2B) NMDA-R subunits were expressed by cultured Schwann cells and upregulated in sciatic nerves following crush injury. The ability of LRP1 ligands to activate ERK1/2 (also known as MAPK3 and MAPK1, respectively) and promote Schwann cell migration required the NMDA-R. NR1 gene silencing compromised Schwann cell survival. Injection of the LRP1 ligands tissue-type plasminogen activator (tPA, also known as PLAT) or MMP9-PEX into crush-injured sciatic nerves activated ERK1/2 in Schwann cells in vivo, and the response was blocked by systemic treatment with the NMDA-R inhibitor MK801. tPA was unique among the LRP1 ligands examined because tPA activated cell signaling and promoted Schwann cell migration by interacting with the NMDA-R independently of LRP1, albeit with delayed kinetics. These results define the NMDA-R as a Schwann cell signaling receptor for protein ligands and a major regulator of Schwann cell physiology, which may be particularly important in peripheral nervous system (PNS) injury. PMID- 26272920 TI - Polycomb RING1A- and RING1B-dependent histone H2A monoubiquitylation at pericentromeric regions promotes S-phase progression. AB - The functions of polycomb products extend beyond their well-known activity as transcriptional regulators to include genome duplication processes. Polycomb activities during DNA replication and DNA damage repair are unclear, particularly without induced replicative stress. We have used a cellular model of conditionally inactive polycomb E3 ligases (RING1A and RING1B), which monoubiquitylate lysine 119 of histone H2A (H2AK119Ub), to examine DNA replication in unperturbed cells. We identify slow elongation and fork stalling during DNA replication that is associated with the accumulation of mid and late S phase cells. Signs of replicative stress and colocalisation of double-strand breaks with chromocenters, the sites of coalesced pericentromeric heterocromatic (PCH) domains, were enriched in cells at mid S-phase, the stage at which PCH is replicated. Altered replication was rescued by targeted monoubiquitylation of PCH through methyl-CpG binding domain protein 1. The acute senescence associated with the depletion of RING1 proteins, which is mediated by p21 (also known as CDKN1A) upregulation, could be uncoupled from a response to DNA damage. These findings link cell proliferation and the polycomb proteins RING1A and RING1B to S-phase progression through a specific function in PCH replication. PMID- 26272921 TI - FoxO1 inhibits transcription and membrane trafficking of epithelial Na+ channel. AB - The epithelial Na(+) channel (ENaC), regulated by insulin, is of fundamental importance in the control of Na(+) reabsorption in the distal nephron. The potential role of Forkhead box O1 (FoxO1), downstream of insulin signaling, in the regulation of ENaC remains to be investigated. Here, we found that the overexpression of a constitutively active form of FoxO1 (ADA-FoxO1) suppressed the mRNA level of the ENaC alpha subunit (alpha-ENaC; also known as SCCN1A) and the apical density of ENaC in mouse cortical collecting duct (mCCD) cells. Conversely, knockdown of FoxO1 increased the apical membrane levels of alpha-ENaC and Na(+) transport under basal conditions. Insulin elevated alpha-ENaC expression and induced FoxO1 phosphorylation; however, the increase in alpha-ENaC and phosphorylated FoxO1 expression observed with insulin treatment was blunted ~ 60% in cells expressing ADA-FoxO1. Moreover, insulin induced the interaction between phosphorylated FoxO1 and 14-3-3epsilon, indicating that FoxO1 phosphorylation promotes ENaC membrane trafficking by binding to 14-3-3epsilon. FoxO1 also suppressed activity of the alpha-ENaC promoter, and the putative FoxO1 target site is located in the -500 to -200 nt region of the alpha-ENaC promoter. These findings indicate that FoxO1 is a key negative regulatory factor in the insulin-dependent control of ENaC expression and forward trafficking in mCCD epithelia. PMID- 26272922 TI - Cellular functions of Rab GTPases at a glance. AB - Rab GTPases control intracellular membrane traffic by recruiting specific effector proteins to restricted membranes in a GTP-dependent manner. In this Cell Science at a Glance and the accompanying poster, we highlight the regulation of Rab GTPases by proteins that control their membrane association and activation state, and provide an overview of the cellular processes that are regulated by Rab GTPases and their effectors, including protein sorting, vesicle motility and vesicle tethering. We also discuss the physiological importance of Rab GTPases and provide examples of diseases caused by their dysfunctions. PMID- 26272924 TI - Opinion: Is CRISPR-based gene drive a biocontrol silver bullet or global conservation threat? PMID- 26272923 TI - Origin of colossal magnetoresistance in LaMnO3 manganite. AB - Phase separation is a crucial ingredient of the physics of manganites; however, the role of mixed phases in the development of the colossal magnetoresistance (CMR) phenomenon still needs to be clarified. We report the realization of CMR in a single-valent LaMnO3 manganite. We found that the insulator-to-metal transition at 32 GPa is well described using the percolation theory. Pressure induces phase separation, and the CMR takes place at the percolation threshold. A large memory effect is observed together with the CMR, suggesting the presence of magnetic clusters. The phase separation scenario is well reproduced, solving a model Hamiltonian. Our results demonstrate in a clean way that phase separation is at the origin of CMR in LaMnO3. PMID- 26272925 TI - Reply to Jee et al. and Israelachvili and Drummond: Lubricant films do not fluidize in intermittent stick-slip friction. PMID- 26272926 TI - Scrutinizing evidence of no dilatancy upon stick-slip of confined fluids. PMID- 26272927 TI - On the conformational state of molecules in molecularly thin shearing films. PMID- 26272928 TI - Obstructive sleep apnoea and cardiovascular calcification. PMID- 26272930 TI - Correction. PMID- 26272929 TI - Look back with (some) anger, and a lot of pleasure. PMID- 26272932 TI - Deficiencies Identified in Dated Case Reports Associated With Herbalife. PMID- 26272933 TI - Single-Dose Vaccines. PMID- 26272934 TI - Reply to Nalin. PMID- 26272936 TI - P-Glycoprotein Transport of Neurotoxic Pesticides. AB - P-glycoprotein (P-gp) has been associated with a number of neurodegenerative diseases, including Parkinson's disease, although the mechanisms remain unclear. Altered transport of neurotoxic pesticides has been proposed in Parkinson's disease, but it is unknown whether these pesticides are P-gp substrates. We used three in vitro transport models, stimulation of ATPase activity, xenobiotic induced cytotoxicity, and inhibition of rhodamine-123 efflux, to evaluate P-gp transport of diazinon, dieldrin, endosulfan, ivermectin, maneb, 1-methyl-4-phenyl 4-phenylpyridinium ion (MPP(+)), and rotenone. Diazinon and rotenone stimulated ATPase activity in P-gp-expressing membranes, with Vmax values of 22.4 +/- 2.1 and 16.8 +/- 1.0 nmol inorganic phosphate/min per mg protein, respectively, and Km values of 9.72 +/- 3.91 and 1.62 +/- 0.51 uM, respectively, compared with the P-gp substrate verapamil, with a Vmax of 20.8 +/- 0.7 nmol inorganic phosphate/min per mg protein and Km of 0.871 +/- 0.172 MUM. None of the other pesticides stimulated ATPase activity. We observed an increased resistance to MPP(+) and rotenone in LLC-MDR1-WT cells compared with LLC-vector cells, with 15.4- and 2.2-fold increases in EC50 values, respectively. The resistance was reversed in the presence of the P-gp inhibitor verapamil. None of the other pesticides displayed differential cytotoxicity. Ivermectin was the only pesticide to inhibit P-gp transport of rhodamine-123, with an IC50 of 0.249 +/- 0.048 MUM. Our data demonstrate that dieldrin, endosulfan, and maneb are not P-gp substrates or inhibitors. We identified diazinon, MPP(+), and rotenone as P-gp substrates, although further investigation is needed to understand the role of P-gp transport in their disposition in vivo and associations with Parkinson's disease. PMID- 26272935 TI - Human Neutrophils Are Primed by Chemoattractant Gradients for Blocking the Growth of Aspergillus fumigatus. AB - The contribution of human neutrophils to the protection against fungal infections by Aspergillus fumigatus is essential but not fully understood. Whereas healthy people can inhale spores of A. fumigatus without developing disease, neutropenic patients and those receiving immunosuppressive drugs have a higher incidence of invasive fungal infections. To study the role of neutrophils in protection against A. fumigatus infections, we developed an in vitro assay in which the interactions between human neutrophils and A. fumigatus were observed in real time, at single-cell resolution, in precisely controlled conditions. We measured the outcomes of neutrophil-fungus interactions and found that human neutrophils have a limited ability to migrate toward A. fumigatus and block the growth of A. fumigatus conidia (proportion with growth blocked, 69%). The blocking ability of human neutrophils increased to 85.1% when they were stimulated by uniform concentrations of fMLP and was enhanced further, to 99.4%, in the presence of chemoattractant gradients. Neutrophils from patients receiving immunosuppressive treatment after transplantation were less effective against the fungus than those from healthy donors, and broader heterogeneity exists between patients, compared with healthy individuals. Further studies using this microfluidic platform will help understand the relevance of innate immune deficiencies responsible for the higher risk of fungal infections in patients with immunosuppressive disease. PMID- 26272938 TI - Multisite Thrombus Imaging and Fibrin Content Estimation With a Single Whole-Body PET Scan in Rats. AB - OBJECTIVE: Thrombosis is a leading cause of morbidity and mortality worldwide. Current diagnostic strategies rely on imaging modalities that are specific for distinct vascular territories, but a thrombus-specific whole-body imaging approach is still missing. Moreover, imaging techniques to assess thrombus composition are underdeveloped, although therapeutic strategies may benefit from such technology. Therefore, our goal was to test whether positron emission tomography (PET) with the fibrin-binding probe (64)Cu-FBP8 allows multisite thrombus detection and fibrin content estimation. APPROACH AND RESULTS: Thrombosis was induced in Sprague-Dawley rats (n=32) by ferric chloride application on both carotid artery and femoral vein. (64)Cu-FBP8-PET/CT imaging was performed 1, 3, or 7 days after thrombosis to detect thrombus location and to evaluate age-dependent changes in target uptake. Ex vivo biodistribution, autoradiography, and histopathology were performed to validate imaging results. Arterial and venous thrombi were localized on fused PET/CT images with high accuracy (97.6%; 95% confidence interval, 92-100). A single whole-body PET/MR imaging session was sufficient to reveal the location of both arterial and venous thrombi after (64)Cu-FBP8 administration. PET imaging showed that probe uptake was greater in younger clots than in older ones for both arterial and venous thrombosis (P<0.0001). Quantitative histopathology revealed an age-dependent reduction of thrombus fibrin content (P<0.001), consistent with PET results. Biodistribution and autoradiography further confirmed the imaging findings. CONCLUSIONS: We demonstrated that (64)Cu-FBP8-PET is a feasible approach for whole-body thrombus detection and that molecular imaging of fibrin can provide, noninvasively, insight into clot composition. PMID- 26272941 TI - A coalition partnership of vision health through a health-promoting school program for primary school students in Taiwan. AB - Myopia, the most common refractive error, is the most common cause of avoidable visual impairment among children and has reached epidemic proportions among children and young adults in urban areas of East and Southeast Asia that contain populations of Chinese ancestry. Moreover, vision health is an important theme of the health-promoting school program issued by the Ministry of Education in Taiwan. The aim of this study is to assess the impact of pre- and post intervention proposed by the health-promoting school (HPS) model. The objectives are to understand whether the HPS model influenced the vision screening results and the attitude, knowledge level, and vision care behavior of the students involved. A prospective cohort study design was used to evaluate a vision health program. Four elementary schools, local education authorities, and one university in northern Taiwan established a coalition partnership to design a six-month program to combat myopia among students. The target population was 6668 school children from local elementary schools. For the purpose of this study, the outcome of visual acuity testing (in logMAR) was analyzed with a sampling of 373 school children (aged 11-12 years old) who were chosen from high prevalence of poor vision classes. After the HPS program, the attitudes, behaviors, and knowledge levels of the school children regarding vision health were significantly improved. The pre-intervention mean logMAR of all participating students ( N = 373) was -.10, which increased to -.19 after the intervention. Analysis using the Wilcoxon signed-rank test showed that the logMAR value was significantly improved after the intervention ( t = 2.13, p < 0.05). Our findings highlight the relevance and effectiveness of the coalition's efforts, which reinforces the usefulness of co-operatively implementing the HPS program. PMID- 26272939 TI - Gallstone Disease and the Risk of Ischemic Heart Disease. AB - OBJECTIVE: Gallstone disease (GSD) is related to multiple cardiovascular risk factors; the present study was to prospectively examine the association between GSD and ischemic heart disease (IHD). APPROACH AND RESULTS: We examined the association of GSD with IHD among 199 292 men and 288 081 women aged 30-79 years in the China Kadoorie Biobank study. Participants with cancer, heart disease, and stroke at baseline were excluded. Cox proportional hazards regression model was used to estimate the association of GSD with IHD. The prevalence of self-reported GSD was 3.7% in men and 7.3% in women at baseline. During 3 431 124 person-years of follow-up between 2004 and 2013 (median, 7.2 years), we documented 10 245 incident IHD cases in men and 14 714 in women. As compared with men without GSD at baseline, the multivariate-adjusted hazard ratio for IHD was 1.11 (95% confidence interval, 1.02-1.22) for men with GSD; the respective hazard ratio was 1.27 (95% confidence interval, 1.20-1.34) in women and 1.23 (95% confidence interval, 1.17-1.28) in the whole cohort. The sex difference in IHD risk associated with GSD was statistically significant (P=0.009 for interaction with sex). In addition, we found that the association between GSD and IHD was stronger in nonhypertensive than in hypertensive women (P<0.001 for interaction). CONCLUSIONS: In this large prospective study, the presence of GSD was associated with an increased risk of incident IHD, independent of other risk factors of cardiovascular disease. Our findings suggest novel prevention strategy to mitigate heart disease through improvement of gastrointestinal health. PMID- 26272940 TI - Drug-Free Platelets Can Act as Seeds for Aggregate Formation During Antiplatelet Therapy. AB - OBJECTIVE: Reduced antiplatelet drug efficacy occurs in conditions of increased platelet turnover, associated with increased proportions of drug-free, that is, uninhibited, platelets. Here, we detail mechanisms by which drug-free platelets promote platelet aggregation in the face of standard antiplatelet therapy. APPROACH AND RESULTS: To model standard antiplatelet therapy, platelets were treated in vitro with aspirin, the P2Y12 receptor blocker prasugrel active metabolite, or aspirin plus prasugrel active metabolite. Different proportions of uninhibited platelets were then introduced. Light transmission aggregometry analysis demonstrated clear positive associations between proportions of drug free platelets and percentage platelet aggregation in response to a range of platelet agonists. Using differential platelet labeling coupled with advanced flow cytometry and confocal imaging we found aggregates formed in mixtures of aspirin-inhibited platelets together with drug-free platelets were characterized by intermingled platelet populations. This distribution is in accordance with the ability of drug-free platelets to generate thromboxane A2 and so drive secondary platelet activation. Conversely, aggregates formed in mixtures of prasugrel active metabolite-inhibited or aspirin plus prasugrel active metabolite-inhibited platelets together with drug-free platelets were characterized by distinct cores of drug-free platelets. This distribution is consistent with the ability of drug free platelets to respond to the secondary activator ADP. CONCLUSIONS: These experiments are the first to image the interactions of inhibited and uninhibited platelets in the formation of platelet aggregates. They demonstrate that a general population of platelets can contain subpopulations that respond strikingly differently to overall stimulation of the population and so act as the seed for platelet aggregation. PMID- 26272937 TI - HU-444, a Novel, Potent Anti-Inflammatory, Nonpsychotropic Cannabinoid. AB - Cannabidiol (CBD) is a component of cannabis, which does not cause the typical marijuana-type effects, but has a high potential for use in several therapeutic areas. In contrast to Delta(9)-tetrahydrocannabinol (Delta(9)-THC), it binds very weakly to the CB1 and CB2 cannabinoid receptors. It has potent activity in both in vitro and in vivo anti-inflammatory assays. Thus, it lowers the formation of tumor necrosis factor (TNF)-alpha, a proinflammatory cytokine, and was found to be an oral antiarthritic therapeutic in murine collagen-induced arthritis in vivo. However, in acidic media, it can cyclize to the psychoactive Delta(9)-THC. We report the synthesis of a novel CBD derivative, HU-444, which cannot be converted by acid cyclization into a Delta(9)-THC-like compound. In vitro HU-444 had anti-inflammatory activity (decrease of reactive oxygen intermediates and inhibition of TNF-alpha production by macrophages); in vivo it led to suppression of production of TNF-alpha and amelioration of liver damage as well as lowering of mouse collagen-induced arthritis. HU-444 did not cause Delta(9)-THC-like effects in mice. We believe that HU-444 represents a potential novel drug for rheumatoid arthritis and other inflammatory diseases. PMID- 26272942 TI - Cellular mechanisms of MR regulation of adipose tissue physiology and pathophysiology. AB - In addition to the well-documented expression and activity of the mineralocorticoid receptor (MR) in the kidney, in the last decade research on MR has also revealed its important role in regulating functions of extrarenal tissues, including adipose tissue, where MR is involved in adipocyte fundamental processes such as differentiation, autophagy and adipokine secretion. MR expression is increased in adipose tissue of murine models of obesity and in obese human subjects, suggesting that over-activation of the mineralocorticoid signaling leads to dysfunctional adipocyte and associated metabolic disorders. Notably, pharmacological blockade of MR prevents metabolic dysfunctions observed in obese mice and suggests a potential therapeutic use of MR antagonists in the treatment of obesity and metabolic syndrome. However, the molecular pathways affected by MR blockade have been poorly investigated. This review summarizes the functions of MR in the adipocyte, discusses potential signaling pathways mediating MR action, and describes post-translational modifications regulating its activity. PMID- 26272943 TI - Amyloid fibrils are the molecular trigger of inflammation in Parkinson's disease. AB - Parkinson's disease (PD) is an age-related movement disorder characterized by a progressive degeneration of dopaminergic neurons in the midbrain. Although the presence of amyloid deposits of alpha-synuclein (alpha-syn) is the main pathological feature, PD brains also present a severe permanent inflammation, which largely contributes to neuropathology. Although alpha-syn has recently been implicated in this process, the molecular mechanisms underlying neuroinflammation remain unknown. In the present study, we investigated the ability of different alpha-syn aggregates to trigger inflammatory responses. We showed that alpha-syn induced inflammation through activation of Toll-like receptor 2 (TLR2) and the nucleotide oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome only when folded as amyloid fibrils. Oligomeric species, thought to be the primary species responsible for the disease, were surprisingly unable to trigger the same cascades. As neuroinflammation is a key player in PD pathology, these results put fibrils back to the fore and rekindles discussions about the primary toxic species contributing to the disease. Our data also suggest that the inflammatory properties of alpha-syn fibrils are linked to their intrinsic structure, most probably to their cross-beta structure. Since fibrils of other amyloids induce similar immunological responses, we propose that the canonical fibril-specific cross-beta structure represents a new generic motif recognized by the innate immune system. PMID- 26272945 TI - Review: High-performance computing to detect epistasis in genome scale data sets. AB - It is becoming clear that most human diseases have a complex etiology that cannot be explained by single nucleotide polymorphisms (SNPs) or simple additive combinations; the general consensus is that they are caused by combinations of multiple genetic variations. The limited success of some genome-wide association studies is partly a result of this focus on single genetic markers. A more promising approach is to take into account epistasis, by considering the association of multiple SNP interactions with disease. However, as genomic data continues to grow in resolution, and genome and exome sequencing become more established, the number of combinations of variants to consider increases rapidly. Two potential solutions should be considered: the use of high performance computing, which allows us to consider a larger number of variables, and heuristics to make the solution more tractable, essential in the case of genome sequencing. In this review, we look at different computational methods to analyse epistatic interactions within disease-related genetic data sets created by microarray technology. We also review efforts to use epistatic analysis results to produce biomarkers for diagnostic tests and give our views on future directions in this field in light of advances in sequencing technology and variants in non-coding regions. PMID- 26272944 TI - Efficient entry of cell-penetrating peptide nona-arginine into adherent cells involves a transient increase in intracellular calcium. AB - Understanding the mechanism of entry of cationic peptides such as nona-arginine (R9) into cells remains an important challenge to their use as efficient drug delivery vehicles. At nanomolar to low micromolar R9 concentrations and at physiological temperature, peptide entry involves endocytosis. In contrast, at a concentration >=10 MUM, R9 induces a very effective non-endocytic entry pathway specific for cationic peptides. We found that a similar entry pathway is induced at 1-2 MUM concentrations of R9 if peptide application is accompanied by a rapid temperature drop to 15 degrees C. Both at physiological and at sub-physiological temperatures, this entry mechanism was inhibited by depletion of the intracellular ATP pool. Intriguingly, we found that R9 at 10-20 MUM and 37 degrees C induces repetitive spikes in intracellular Ca(2+) concentration. This Ca(2+) signalling correlated with the efficiency of the peptide entry. Pre loading cells with the Ca(2+) chelator BAPTA (1,2-bis(o-aminophenoxy)ethane N,N,N',N'-tetraacetic acid) inhibited both Ca(2+) spikes and peptide entry, suggesting that an increase in intracellular Ca(2+) precedes and is required for peptide entry. One of the hallmarks of Ca(2+) signalling is a transient cell surface exposure of phosphatidylserine (PS), a lipid normally residing only in the inner leaflet of the plasma membrane. Blocking the accessible PS with the PS binding domain of lactadherin strongly inhibited non-endocytic R9 entry, suggesting the importance of PS externalization in this process. To conclude, we uncovered a novel mechanistic link between calcium signalling and entry of cationic peptides. This finding will enhance our understanding of the properties of plasma membrane and guide development of future drug-delivery vehicles. PMID- 26272946 TI - N-terminal-mediated oligomerization of DnaA drives the occupancy-dependent rejuvenation of the protein on the membrane. AB - DnaA, the initiator of chromosome replication in most known eubacteria species, is activated once per cell division cycle. Its overall activity cycle is driven by ATP hydrolysis and ADP-ATP exchange. The latter can be promoted by binding to specific sequences on the chromosome and/or to acidic phospholipids in the membrane. We have previously shown that the transition into an active form (rejuvenation) is strongly co-operative with respect to DnaA membrane occupancy. Only at low membrane occupancy is DnaA reactivation efficiently catalysed by the acidic phospholipids. The present study was aimed at unravelling the molecular mechanism underlying the occupancy-dependent DnaA rejuvenation. We found that truncation of the DnaA N-terminal completely abolishes the co-operative transformation between the high and low occupancy states (I and II respectively) without affecting the membrane binding. The environmentally sensitive fluorophore specifically attached to the N-terminal cysteines of DnaA reported on occupancy correlated changes in its vicinity. Cross-linking of DnaA with a short homobifunctional reagent revealed that state II of the protein on the membrane corresponds to a distinct oligomeric form of DnaA. The kinetic transition of DnaA on the membrane surface is described in the present study by a generalized 2D condensation phase transition model, confirming the existence of two states of DnaA on the membrane and pointing to the possibility that membrane protein density serves as an on-off switch in vivo. We conclude that the DnaA conformation attained at low surface density drives its N-terminal-mediated oligomerization, which is presumably a pre-requisite for facilitated nt exchange. PMID- 26272947 TI - Strategies for High-Quality Nutrition Therapy in Brazil. AB - Strategies for improving nutrition therapy (NT) are of utmost importance in any healthcare system. The identification and treatment of malnourished patients improves clinical outcome and reduces the length of hospital length of stay and the associated costs. In particular, federal policy regulating the use of NT in Brazil and reimbursement of enteral nutrition (EN) treatment were 2 powerful mechanisms that stimulated the development of nutrition care. Basic and clinical research have also contributed to best practices in NT, thereby highlighting the need for nutrition therapy teams, quality indicators, and nutrition education for the delivery of high-quality NT. It is clear that the availability of training and continuing education programs in clinical nutrition is key to improving nutrition awareness and care, as well as patient outcome. On the basis of our experience, we recommend the Brazilian model as a strategy for improving nutrition care, with appropriate and necessary adaptations made to accommodate different settings. PMID- 26272949 TI - Drug-associated arrhythmia in the military patient. AB - Members of the Armed Forces may be exposed to drugs, or combinations of drugs, with the potential to prolong the QRS or QT intervals. The effect of this is to increase the likelihood of developing dangerous ventricular tachyarrhythmias, including ventricular tachycardia, torsades de pointes or ventricular fibrillation. Common examples of the pharmacological agents associated include antibiotics, antiemetics and antimalarials. Genetic predisposition, electrolyte disturbance, anaesthesia and trauma may exacerbate the proarrhythmic effect of these medications. Screening of recruits does not detect all those with a genetic predisposition to drug-associated arrhythmias, so vigilance in preventing this iatrogenic disorder and recognising and appropriately managing it when present is important. This article explains the physiological basis of arrhythmogenesis, outlines the clinical features and provides guidance on investigation and management, with particular reference to military patients. PMID- 26272948 TI - Experimental evaluation of spatial resolution in phase maps retrieved by transport of intensity equation. AB - The transport of intensity equation (TIE) is a convenient method of obtaining a potential distribution, as it requires only three transmission electron microscopy images with different amounts of defocus. However, the spatial resolution of the TIE phase map has not yet been evaluated experimentally. In this study, we investigated the phase distribution of spherical gold nanoparticles and its dependence on the defocus difference and found that the spatial resolution was finer than 2 nm, even for a defocus difference of 4 um. Theoretical calculations reproduced the experimental results well. PMID- 26272950 TI - Defining the essential anatomical coverage provided by military body armour against high energy projectiles. AB - INTRODUCTION: Body armour is a type of equipment worn by military personnel that aims to prevent or reduce the damage caused by ballistic projectiles to structures within the thorax and abdomen. Such injuries remain the leading cause of potentially survivable deaths on the modern battlefield. Recent developments in computer modelling in conjunction with a programme to procure the next generation of UK military body armour has provided the impetus to re-evaluate the optimal anatomical coverage provided by military body armour against high energy projectiles. METHODS: A systematic review of the literature was undertaken to identify those anatomical structures within the thorax and abdomen that if damaged were highly likely to result in death or significant long-term morbidity. These structures were superimposed upon two designs of ceramic plate used within representative body armour systems using a computerised representation of human anatomy. RESULTS AND CONCLUSIONS: Those structures requiring essential medical coverage by a plate were demonstrated to be the heart, great vessels, liver and spleen. For the 50th centile male anthropometric model used in this study, the front and rear plates from the Enhanced Combat Body Armour system only provide limited coverage, but do fulfil their original requirement. The plates from the current Mark 4a OSPREY system cover all of the structures identified in this study as requiring coverage except for the abdominal sections of the aorta and inferior vena cava. Further work on sizing of plates is recommended due to its potential to optimise essential medical coverage. PMID- 26272951 TI - Gold Nanoparticles Increase Endothelial Paracellular Permeability by Altering Components of Endothelial Tight Junctions, and Increase Blood-Brain Barrier Permeability in Mice. AB - Gold nanoparticles (Au-NPs) are being increasingly used as constituents in cosmetics, biosensors, bioimaging, photothermal therapy, and targeted drug delivery. This elevated exposure to Au-NPs poses systemic risks in humans, particularly risks associated with the biodistribution of Au-NPs and their potent interaction with biological barriers. We treated human umbilical vein endothelial cells with Au-NPs and comprehensively examined the expression levels of tight junction (TJ) proteins such as occludin, claudin-5, junctional adhesion molecules, and zonula occludens-1 (ZO-1), as well as endothelial paracellular permeability and the intracellular signaling required for TJ organization. Moreover, we validated the effects of Au-NPs on the integrity of TJs in mouse brain microvascular endothelial cells in vitro and obtained direct evidence of their influence on blood-brain barrier (BBB) permeability in vivo. Treatment with Au-NPs caused a pronounced reduction of PKCzeta-dependent threonine phosphorylation of occludin and ZO-1, which resulted in the instability of endothelial TJs and led to proteasome-mediated degradation of TJ components. This impairment in the assembly of TJs between endothelial cells increased the permeability of the transendothelial paracellular passage and the BBB. Au-NPs increased endothelial paracellular permeability in vitro and elevated BBB permeability in vivo. Future studies must investigate the direct and indirect toxicity caused by Au-NP-induced endothelial TJ opening and thereby address the double-edged-sword effect of Au-NPs. PMID- 26272954 TI - Correction. PMID- 26272953 TI - Omeprazole Attenuates Pulmonary Aryl Hydrocarbon Receptor Activation and Potentiates Hyperoxia-Induced Developmental Lung Injury in Newborn Mice. AB - Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in human preterm infants and a similar lung phenotype characterized by alveolar simplification in newborn mice. Omeprazole (OM) is a proton pump inhibitor that is used to treat humans with gastric acid related disorders. OM-mediated aryl hydrocarbon receptor (AhR) activation attenuates acute hyperoxic lung injury (HLI) in adult mice. Whether OM activates pulmonary AhR and protects C57BL/6J newborn mice against hyperoxia-induced developmental lung (alveolar and pulmonary vascular simplification, inflammation, and oxidative stress) injury (HDLI) is unknown. Therefore, we tested the hypothesis that OM will activate pulmonary AhR and mitigate HDLI in newborn mice. Newborn mice were treated daily with i.p. injections of OM at doses of 10 (OM10) or 25 (OM25) mg/kg while being exposed to air or hyperoxia (FiO2 of 85%) for 14 days, following which their lungs were harvested to determine alveolarization, pulmonary vascularization, inflammation, oxidative stress, vascular injury, and AhR activation. To our surprise, hyperoxia induced alveolar and pulmonary vascular simplification, inflammation, oxidative stress, and vascular injury were augmented in OM25-treated animals. These findings were associated with attenuated pulmonary vascular endothelial growth factor receptor 2 expression and decreased pulmonary AhR activation in the OM25 group. We conclude that contrary to our hypothesis, OM decreases functional activation of pulmonary AhR and potentiates HDLI in newborn mice. These observations are consistent with our previous findings, which suggest that AhR activation plays a protective role in HDLI in newborn mice. PMID- 26272952 TI - Integrated Model of Chemical Perturbations of a Biological Pathway Using 18 In Vitro High-Throughput Screening Assays for the Estrogen Receptor. AB - We demonstrate a computational network model that integrates 18 in vitro, high throughput screening assays measuring estrogen receptor (ER) binding, dimerization, chromatin binding, transcriptional activation, and ER-dependent cell proliferation. The network model uses activity patterns across the in vitro assays to predict whether a chemical is an ER agonist or antagonist, or is otherwise influencing the assays through a manner dependent on the physics and chemistry of the technology platform ("assay interference"). The method is applied to a library of 1812 commercial and environmental chemicals, including 45 ER positive and negative reference chemicals. Among the reference chemicals, the network model correctly identified the agonists and antagonists with the exception of very weak compounds whose activity was outside the concentration range tested. The model agonist score also correlated with the expected potency class of the active reference chemicals. Of the 1812 chemicals evaluated, 111 (6.1%) were predicted to be strongly ER active in agonist or antagonist mode. This dataset and model were also used to begin a systematic investigation of assay interference. The most prominent cause of false-positive activity (activity in an assay that is likely not due to interaction of the chemical with ER) is cytotoxicity. The model provides the ability to prioritize a large set of important environmental chemicals with human exposure potential for additional in vivo endocrine testing. Finally, this model is generalizable to any molecular pathway for which there are multiple upstream and downstream assays available. PMID- 26272955 TI - Spontaneous regression of intracranial aneurysm following remote ruptured aneurysm treatment with pipeline stent assisted coiling. AB - Spontaneous aneurysm regression is a rare phenomenon. We present the interesting case of a 54-year-old woman who was admitted with a Hunt/Hess grade IV, Fisher grade III subarachnoid hemorrhage and multiple intracranial aneurysms. She was treated with coiling of the largest paraclinoid aneurysm and placement of a flow diverting pipeline embolization device that covered all internal carotid artery (ICA) aneurysms. A follow-up angiogram at 6 months showed remodeling of the ICA with complete obliteration of all treated aneurysms. A distant, untreated, right frontal M2 aneurysm regressed spontaneously, after the flow was diverted away from it with the stent. The literature is reviewed, and potential pathophysiological mechanisms leading to aneurysm regression are discussed. PMID- 26272956 TI - Correction. PMID- 26272957 TI - Submandibular schwannoma: is excision a 'gold standard treatment'? AB - A 58-year-old man was referred to ear, nose and throat (ENT) with an 8-week history of painless right submandibular swelling with no history of weight loss, dysphagia or difficulty with mastication. On examination, there was enlargement of the right submandibular gland, which was diffuse, nodular and firm; but no calcification of the duct or cervical lymphadenopathy. ENT examination including fibreoptic laryngoscopy was normal. Fine-needle aspiration of the lump was inconclusive. Neck ultrasound scan showed a well-defined 3 cm * 3.8 cm * 4.3 cm heterogeneous mass with significant internal vascularity, anterior to the right submandibular gland. MRI (T2-weighted MRI) revealed a neurogenic tumour or a non sarcomatous soft tissue lesion. Complete excision of the lump was performed by intracapsular dissection and the specimen was submitted for histology, which confirmed the diagnosis of 'Ancient schwannoma' of the submandibular gland. The management resulted in complete resolution of symptoms with no cranial nerve deficits. PMID- 26272960 TI - Haemoperitoneum secondary to intrahepatic gallbladder perforation. AB - A 70-year-old man presented to the accident and emergency department with a 1-day history of right upper quadrant pain and nausea. Examination revealed mild tenderness in the right upper quadrant but no evidence of peritonism or haemodynamic instability. The patient was admitted to the general surgical ward with a diagnosis of cholecystitis and remained stable overnight. In the morning, he developed acute severe pain in the upper abdomen. Examination found him to be tachycardic, tachypnoeic and to have peritonism in the upper abdomen. An urgent CT scan demonstrated cholecystitis but also a small amount of fluid in the pelvis, with Hounsfield units suggestive of blood. The patient proceeded to laparotomy and was found to have massive haemoperitoneum secondary to intrahepatic gallbladder perforation causing liver capsule tear. Cholecystectomy was performed and the liver packed until haemostasis was achieved. The patient made an uneventful recovery. PMID- 26272958 TI - Milk-sensitive eosinophilic gastroenteritis in a 2-month-old boy. AB - Eosinophilic gastroenteritis is a rare disease of unknown aetiology, characterised by eosinophilic infiltration of the gastrointestinal wall with various gastrointestinal manifestations. Clinical presentation and radiological findings are non-specific and there is an overlap with more frequent childhood diseases requiring a high degree of clinical suspicion for accurate diagnosis. We describe a 2-month-old boy with prolonged diarrhoea, vomiting and food refusal. Diagnosis was settled by histology. The treatment with elemental diet was successful, with clinical resolution and catch-up growth. PMID- 26272961 TI - Xanthogranulomatous cystitis with malacoplakia, leading to spontaneous intraperitoneal perforation of the urinary bladder in a 9-year-old girl. AB - A 9-year-old girl presented with sudden onset continuous abdomen pain, oliguria and constipation for 2 days. Ultrasound of the abdomen and voiding cystourethrography revealed intraperitoneal perforation of the urinary bladder. Cystoscopy showed two perforations at the dome of the bladder. Open surgical repair of the perforations was performed and biopsy was taken from their edges. Histopathological examination of biopsied material revealed malacoplakia with xanthogranulomatous cystitis. The patient was doing well at 15 months follow-up. Xanthogranulomatous cystitis with malacoplakia leading to spontaneous bladder perforation has not been reported earlier in the English literature. PMID- 26272959 TI - Malignant cutaneous lesions. PMID- 26272962 TI - Right atrial myxoma mimicking tricuspid stenosis. AB - A 62-year-old man presented to the cardiology clinic with symptoms of fatigue, shortness of breath and swelling in the abdomen and legs. A pedunculated mobile mass with a short stalk in the right atrium was found to originate from the inferior vena caval opening and prolapse into the right ventricle through a tricuspid valve during diastole in echocardiography. The patient was referred to our department and surgery was planned for right atrial myxomas diagnosis. The mass with surrounding tissue was surgically removed using the cardiopulmonary bypass method. No postoperative complications were seen in the currently asymptomatic patient who is still under our follow-up schedule. PMID- 26272964 TI - Varicella zoster virus infection is an unusual cause of splenic rupture. AB - A 22-year-old man presented with a 1-day history of severe abdominal pain. He developed a generalised vesicular rash 12 h prior to admission. On examination, he was maximally tender with peritonism in the lower abdomen. Working diagnosis was perforated appendix and a decision to investigate with CT was made, which showed intra-abdominal haemorrhage likely arising from a ruptured spleen. After a period of observation, he subsequently underwent laparotomy and emergency splenectomy. Viral PCR from vesicular fluid was positive for varicella zoster virus. Viral serology was otherwise negative. PMID- 26272963 TI - The woman without a history. AB - The differential diagnosis for altered mental status (AMS) is broad and aetiological pathologies can arise from nearly all organs and body systems. Further complicating the matter, the altered patient is poorly suited to provide a comprehensive and accurate historical account. Thus, the physician must rely on collateral information, laboratories and imaging, and their own clinical suspicion. We present the case of a 75-year-old woman, found prone in her home with AMS, who was unable to provide a history. As her hospital stay evolved, we were forced to consider the entire breadth of possible causes of AMS. Eventually, the patient was found to have cerebral venous thrombosis, the significant extent of which is rarely reported. During the course of caring for the patient, we were reminded of the importance of remaining unbiased and unanchored while attempting to identify the source of the patient's ailment. PMID- 26272965 TI - Spontaneous coronary artery dissection: the management dilemma continues. AB - Spontaneous coronary artery dissection (SCAD) is an increasingly recognised cause of acute coronary syndrome, particularly in women. A 36-year-old Caucasian woman presented to our hospital with sudden onset chest pain and was diagnosed with a non-ST elevation myocardial infarction. Coronary angiography revealed mid and distal left anterior descending artery (LAD) dissection with distal LAD occlusion. A short segment of apical LAD filled late with incomplete opacification (Thrombolysis In Myocardial Infarction (TIMI) 1 flow). A decision was made to treat the patient conservatively, with subsequent resolution of dissection over the next 3 months. Our patient made a good clinical recovery with healing of her affected coronary vasculature on subsequent angiogram. The case illustrates that SCAD can be managed conservatively with antiplatelet agents, beta-blockers, heparin and statins, if the patient is haemodynamically stable and coronary flow is adequate. PMID- 26272966 TI - Idiopathic septic arthritis of a lumbar facet joint associated with paraspinal abscess. AB - A 48-year-old woman presented with a 1-month history of severe lower back pain on a background of 24 h of mild fever and general tiredness with an associated right sided foot drop. Five weeks after the onset and with no improvement in symptoms in spite of analgesia and physiotherapy, the patient had a lumbar spine MRI which demonstrated a collection extending from the facet joints of L5 and L6 to the iliacus muscle on the right. A CT-guided aspiration was performed with a lengthy hospital stay for intravenous antibiotic treatment. The culture and sensitivity study of the aspirate isolated Streptococcus pneumoniae. PMID- 26272967 TI - Biliary duct hamartomas in polycystic liver disease. PMID- 26272968 TI - Calcinosis universalis in adult-onset dermatomyositis. PMID- 26272969 TI - Progressive back pain due to epidural hygroma: an infrequent complication of lumbar puncture in adults. PMID- 26272970 TI - Initial Experience with p64: A Novel Mechanically Detachable Flow Diverter for the Treatment of Intracranial Saccular Sidewall Aneurysms. AB - BACKGROUND AND PURPOSE: Flow diverters are important tools for the treatment of intracranial aneurysms. We report a retrospective evaluation of the safety and efficacy of p64, a fully resheathable, detachable flow diverter, in the endovascular treatment of intracranial sidewall aneurysms. MATERIALS AND METHODS: Results of 121 patients with 130 aneurysms (median neck size, 3 mm; median fundus size, 4 mm), treated from April 2012 through October 2014, were analyzed. Aneurysms were unruptured or beyond the acute SAH phase. Thirteen aneurysms were located in the posterior circulation. Twenty-three aneurysms had previous saccular treatment but no previous parent vessel stent placement. In 19 aneurysms, a combination of coiling and flow diversion was performed. RESULTS: Successful p64 deployment was achieved in 127/130 aneurysms. The average number of p64s used was 1.1 per aneurysm. The rates of transient and permanent morbidity and mortality were 5%, 1.7%, and 0.8%, respectively. Three-month DSA follow-up in 123/130 aneurysms showed complete occlusion in 58.5%. Nine-month DSA follow-up in 93/106 (87.7%) eligible aneurysms showed complete occlusion in 79.6%. Late follow up (median, 496 days) has already been performed in 35 aneurysms, showing complete occlusion in 30 (85.7%). CONCLUSIONS: p64 offers an efficacious treatment option for intracranial sidewall aneurysms with a high aneurysm occlusion and an acceptable complication rate. The possibility of repositioning or removing the device was an advantage. The higher attenuation may lead to fewer devices per case and early aneurysm occlusion. Long-term follow-up data are pending. PMID- 26272971 TI - Improved Image Quality in Head and Neck CT Using a 3D Iterative Approach to Reduce Metal Artifact. AB - BACKGROUND AND PURPOSE: Metal artifacts from dental fillings and other devices degrade image quality and may compromise the detection and evaluation of lesions in the oral cavity and oropharynx by CT. The aim of this study was to evaluate the effect of iterative metal artifact reduction on CT of the oral cavity and oropharynx. MATERIALS AND METHODS: Data from 50 consecutive patients with metal artifacts from dental hardware were reconstructed with standard filtered back projection, linear interpolation metal artifact reduction (LIMAR), and iterative metal artifact reduction. The image quality of sections that contained metal was analyzed for the severity of artifacts and diagnostic value. RESULTS: A total of 455 sections (mean +/- standard deviation, 9.1 +/- 4.1 sections per patient) contained metal and were evaluated with each reconstruction method. Sections without metal were not affected by the algorithms and demonstrated image quality identical to each other. Of these sections, 38% were considered nondiagnostic with filtered back-projection, 31% with LIMAR, and only 7% with iterative metal artifact reduction. Thirty-three percent of the sections had poor image quality with filtered back-projection, 46% with LIMAR, and 10% with iterative metal artifact reduction. Thirteen percent of the sections with filtered back projection, 17% with LIMAR, and 22% with iterative metal artifact reduction were of moderate image quality, 16% of the sections with filtered back-projection, 5% with LIMAR, and 30% with iterative metal artifact reduction were of good image quality, and 1% of the sections with LIMAR and 31% with iterative metal artifact reduction were of excellent image quality. CONCLUSIONS: Iterative metal artifact reduction yields the highest image quality in comparison with filtered back projection and linear interpolation metal artifact reduction in patients with metal hardware in the head and neck area. PMID- 26272972 TI - Flow Diversion versus Standard Endovascular Techniques for the Treatment of Unruptured Carotid-Ophthalmic Aneurysms. AB - BACKGROUND AND PURPOSE: Over the past few years, flow diversion has been increasingly adopted for the treatment of intracranial aneurysms, especially in the paraclinoid and paraophthalmic carotid segment. We compared clinical and angiographic outcomes and complication rates in 2 groups of patients with unruptured carotid-ophthalmic aneurysms treated for 7 years by either standard coil-based techniques or flow diversion. MATERIALS AND METHODS: From February 2006 to December 2013, 162 unruptured carotid-ophthalmic aneurysms were treated endovascularly in 138 patients. Sixty-seven aneurysms were treated by coil-based techniques in 61 patients. Flow diverters were deployed in 95 unruptured aneurysms (77 patients), with additional coiling in 27 patients. Complication rates, clinical outcome, and immediate and long-term angiographic results were retrospectively analyzed. RESULTS: No procedure-related deaths occurred. Four procedure-related thromboembolic events (6.6%) leading to permanent morbidity in 1 case (1.6%) occurred in the coiling group. Neurologic complications were observed in 6 patients (7.8%) in the flow-diversion group, resulting in 3.9% permanent morbidity. No statistically significant difference was found between complication (P = .9) and morbidity rates (P = .6). In the coiling group (median follow-up, 31.5 +/- 24.5 months), recanalization occurred at 1 year in 23/50 (54%) aneurysms and 27/55 aneurysms (50.9%) at the latest follow-up, leading to retreatment in 6 patients (9%). In the flow-diversion group (mean follow-up, 13.5 +/- 10.8 months), 85.3% (35/41) of all aneurysms were occluded after 12 months, and 74.6% (50/67) on latest follow-up. The retreatment rate was 2.1%. Occlusion rates between the 2 groups differed significantly at 12 months (P < .001) and at the latest follow-up (P < .005). CONCLUSIONS: Our retrospective analysis shows better long-term occlusion of carotid-ophthalmic aneurysms after use of flow diverters compared with standard coil-based techniques, without significant differences in permanent morbidity. PMID- 26272975 TI - Morphologic Features of Carotid Plaque Rupture Assessed by Optical Coherence Tomography. AB - BACKGROUND AND PURPOSE: Rupture of the plaque fibrous cap and subsequent thrombosis are the major causes of stroke. This study evaluated morphologic features of plaque rupture in the carotid artery by using optical coherence tomography in vivo. MATERIALS AND METHODS: Thirty-six carotid plaques with high grade stenosis were prospectively imaged by optical coherence tomography. "Plaque rupture" was defined as a plaque containing a cavity that had overlying residual fibrous caps. The fibrous cap thickness was measured at its thinnest part for both ruptured and nonruptured plaques. The distance between the minimum fibrous cap thickness site and the bifurcation point was also measured. Optical coherence tomography identified 24 ruptured and 12 nonruptured plaques. RESULTS: Multiple ruptures were observed in 9 (38%) patients: Six patients had 2 ruptures in the same plaque, 2 patients had 3 ruptures in the same plaque, and 1 patient had 5 ruptures in the same plaque. Most (84%) of the fibrous cap disruptions were identified at the plaque shoulder and near the bifurcation point (within a 4.2-mm distance). The median thinnest cap thickness was 80 MUm (interquartile range, 70 100 MUm), and 95% of ruptured plaques had fibrous caps of <130 MUm. Receiver operating characteristic analysis revealed that a fibrous cap thickness of <130 MUm was the critical threshold value for plaque rupture in the carotid artery. CONCLUSIONS: Plaque rupture was common in high-grade stenosis and was located at the shoulder of the carotid plaque close to the bifurcation. A cap thickness of <130 MUm was the threshold for plaque rupture in the carotid artery. PMID- 26272973 TI - The Contribution of Common Surgically Implanted Hardware to Functional MR Imaging Artifacts. AB - BACKGROUND AND PURPOSE: Blood oxygenation level-dependent MR imaging is increasingly used clinically to noninvasively assess cerebrovascular reactivity and/or language and motor function. However, many patients have metallic implants, which will induce susceptibility artifacts, rendering the functional information uninformative. Here, we calculate and interpret blood oxygenation level-dependent MR imaging artifact impact arising from surgically implanted hardware. MATERIALS AND METHODS: A retrospective analysis of all blood oxygenation level-dependent MRIs (n = 343; B0 = 3T; TE = 35 ms; gradient echo EPI) acquired clinically (year range = 2006-2014) at our hospital was performed. Blood oxygenation level-dependent MRIs were most commonly prescribed for patients with cerebrovascular disease (n = 80) or patients undergoing language or motor localization (n = 263). Artifact volume (cubic centimeters) and its impact on clinical interpretation were determined by a board-certified neuroradiologist. RESULTS: Mean artifact volume associated with intracranial hardware was 4.3 +/- 3.2 cm(3) (range = 1.1-9.4 cm(3)). The mean artifact volume from extracranial hardware in patients with cerebrovascular disease was 28.4 +/- 14.0 cm(3) (range = 6.1-61.7 cm(3)), and in patients with noncerebrovascular disease undergoing visual or motor functional mapping, it was 39.9 (3)+/- 27.0 cm(3) (range = 6.9 77.1 cm(3)). The mean artifact volume for ventriculoperitoneal shunts was 95.7 +/ 39.3 cm(3) (range = 64.0-139.6 cm(3)). Artifacts had no-to-mild effects on clinical interpretability in all patients with intracranial implants. Extracranial hardware artifacts had no-to-moderate impact on clinical interpretability, with the exception of 1 patient with 12 KLS-Martin maxDrive screws with severe artifacts precluding clinical interpretation. All examined ventriculoperitoneal shunts resulted in moderate-to-severe artifacts, limiting clinical interpretation. CONCLUSIONS: Blood oxygenation level-dependent MR imaging yields interpretable functional maps in most patients beyond a small (30 40 cm(3)) artifact surrounding the hardware. Exceptions were ventriculoperitoneal shunts, particularly those with programmable valves and siphon gauges, and large numbers of KLS-Martin maxDrive screws. PMID- 26272976 TI - LEO Baby Stent Use following Balloon-Assisted Coiling: Single- and Dual-Stent Technique--Immediate and Midterm Results of 29 Consecutive Patients. AB - BACKGROUND AND PURPOSE: We report our preliminary results in terms of safety and efficacy in using the low-profile LEO Baby stent for the treatment of large-neck and complex intracranial aneurysms with balloon-then-stent-assisted coiling and single- or dual-stent-assisted coiling. MATERIALS AND METHODS: Clinical and radiologic data of all consecutive patients treated at our institution from September 2012 to October 2013 for an intracranial aneurysm by using a LEO Baby stent were retrospectively analyzed. Immediate and midterm clinical and anatomic follow-up of each patient is reported. RESULTS: Twenty-nine patients with 29 aneurysms were treated with LEO Baby stents at our institution. The mean age of patients was 48 years; 20 patients were women (71%). One patient was treated in the acute phase of a subarachnoid hemorrhage. In 8 procedures, a double-lumen catheter balloon was used for balloon-then-stent-assisted coiling. In 3 cases, a LEO Baby stent was used in a Y-, T-, and telescopic dual-stent configuration. In 18 cases, a single LEO Baby stent was used. In 2 cases, technical failure to deploy the stent resulted in acute parent artery thrombosis. In 3 further cases, thromboembolic complications occurred intraoperatively. MR imaging and angiographic midterm follow-up showed complete aneurysm occlusion for 96% of the followed patients (27/29). Clinical outcome was favorable for all patients followed up. CONCLUSIONS: Results obtained in our study by using the LEO Baby stent for balloon-then-stent and single- or dual-stent-assisted coiling of complex and distally located intracranial aneurysms are encouraging. Incomplete or inadequate opening of the device is a potential cause of laminar blood flow alteration and thrombus formation. PMID- 26272974 TI - Could Statin Use Be Associated with Reduced Recurrence Rates following Coiling in Ruptured Intracranial Aneurysms? AB - BACKGROUND AND PURPOSE: A number of studies have examined the role of matrix metalloproteinases in aneurysm healing following endovascular coiling. Because ruptured aneurysms are known to express higher levels of matrix metalloproteinases, we hypothesized that patients with subarachnoid hemorrhage who were on a statin at the time of coil embolization would have lower aneurysm recanalization and retreatment rates than patients not on statins. MATERIALS AND METHODS: We performed a retrospective chart review of patients who underwent intrasaccular coil embolization of ruptured intracranial aneurysms of <=10 mm with at least 6 months of imaging follow-up. Patients were separated into 2 groups: 1) those on an oral statin medication at the time of coiling, and 2) those who were not. Outcomes studied were aneurysm recurrence and aneurysm retreatment after endovascular coiling. Student t and chi(2) tests were used for statistical significance of differences between groups. RESULTS: One hundred thirty-two patients with 132 ruptured aneurysms were included in our study. Sixteen were on statins (12.1%) and 116 were not (87.9%). The recurrence rate was 6.3% in the statin group (1/16) and 36.2% in the nonstatin group (42/107) (P = .02). Unplanned retreatment rates were 6.3% (1/16) for the statin group and 25.9% (30/116) for the nonstatin group (P = .08). CONCLUSIONS: Statins were associated with a lower rate of aneurysm recurrence following endovascular coiling of small- and medium-sized ruptured aneurysms in this small retrospective study. Further studies are needed to confirm this finding to determine whether statins can be used to reduce recurrence rates in these aneurysms. PMID- 26272977 TI - Clopidogrel Resistance in Neurovascular Stenting: Correlations between Light Transmission Aggregometry, VerifyNow, and the Multiplate. AB - BACKGROUND AND PURPOSE: Clopidogrel resistance is blamed for thromboembolic complications in neurovascular stent placement. Platelet-function assays are weakly standardized. The aim of this study was to correlate the results of 3 different platelet-inhibition measurements (from light transmission aggregometry, the VerifyNow P2Y12 test, and the Multiplate analyzer) and their relation to periprocedural thromboembolic complications in elective neurovascular stent placement. MATERIALS AND METHODS: Clopidogrel resistance was determined on the day of the intervention according to predefined platelet reactivity cutoff values. All 3 tests were performed in 103 consecutive neurovascular stent placement procedures in 97 patients (extracranial, n = 77; intracranial, n = 26). RESULTS: The clopidogrel resistance rates were 47.6% (light transmission aggregometry), 50.5% (VerifyNow), and 35.9% (Multiplate). In 67% of the patients, clopidogrel resistance was present according to at least one method. The correlations of qualitative results that classified a patient as responsive or resistant to clopidogrel were 67.9% for light transmission aggregometry with VerifyNow, 77.7% for light transmission aggregometry with the Multiplate, and 66% for VerifyNow with the Multiplate. Periprocedural thromboembolic complications (n = 9) occurred more frequently in patients who were determined by all 3 methods to be clopidogrel resistant. The difference was most pronounced with light transmission aggregometry (complication rates, 14.4% [clopidogrel-resistant patients] vs 3.7% [clopidogrel-responsive patients]). Sensitivity and specificity rates of clopidogrel resistance in relation to embolic complications were, respectively, 78% and 55% for light transmission aggregometry, 67% and 51% for VerifyNow, and 44% and 67% for the Multiplate. CONCLUSIONS: Clopidogrel resistance is a frequent finding in patients who undergo neurovascular stent placement. The correlations among the different testing methods are only modest and differ considerably. Light transmission aggregometry results seem to correlate with thromboembolic complications more accurately than with VerifyNow and Multiplate point-of-care methods. PMID- 26272978 TI - Prospective Hemorrhage Rates of Cerebral Cavernous Malformations in Children and Adolescents Based on MRI Appearance. AB - BACKGROUND AND PURPOSE: Current classifications of cerebral cavernous malformations focus solely on morphologic aspects. Our aim was to provide a morphologic classification that reflects hemorrhage rates. MATERIALS AND METHODS: We retrospectively categorized 355 cavernous malformations of 70 children and adolescents according to their morphologic appearance on MR imaging and calculated prospective hemorrhage rates on the basis of survival functions for 255 lesions in 25 patients with a radiologic observation period of >180 days. RESULTS: Overall, there were 199 MR imaging examinations with 1558 distinct cavernous malformation observations during a cumulative observation period of 1094.2 lesion-years. The mean hemorrhage rate of all 355 cavernous malformations was 4.5% per lesion-year. According to Kaplan-Meier survival models, Zabramski type I and II cavernous malformations had a significantly higher hemorrhage rate than type III and IV lesions. The presence of acute or subacute blood-degradation products was the strongest indicator for an increased hemorrhage risk (P = .036, Cox regression): The mean annual hemorrhage rate and mean hemorrhage-free interval for cavernous malformations with and without signs of acute or subacute blood degradation products were 23.4% and 22.6 months and 3.4% and 27.9 months, respectively. Dot-sized cavernous malformations, visible in T2* and not or barely visible in T1WI and T2WI sequences, had a mean annual hemorrhage rate of 1.3% and a mean hemorrhage-free interval of 37.8 months. CONCLUSIONS: It is possible to predict hemorrhage rates based on the Zabramski classification. Our findings imply a tripartite classification distinguishing lesions with and without acute or subacute blood degradation products and dot-sized cavernous malformations. PMID- 26272979 TI - Unabridged Analysis of Human Histone H3 by Differential Top-Down Mass Spectrometry Reveals Hypermethylated Proteoforms from MMSET/NSD2 Overexpression. AB - Histones, and their modifications, are critical components of cellular programming and epigenetic inheritance. Recently, cancer genome sequencing has uncovered driver mutations in chromatin modifying enzymes spurring high interest how such mutations change histone modification patterns. Here, we applied Top Down mass spectrometry for the characterization of combinatorial modifications (i.e. methylation and acetylation) on full length histone H3 from human cell lines derived from multiple myeloma patients with overexpression of the histone methyltransferase MMSET as the result of a t(4;14) chromosomal translocation. Using the latest in Orbitrap-based technology for clean isolation of isobaric proteoforms containing up to 10 methylations and/or up to two acetylations, we provide extensive characterization of histone H3.1 and H3.3 proteoforms. Differential analysis of modifications by electron-based dissociation recapitulated antagonistic crosstalk between K27 and K36 methylation in H3.1, validating that full-length histone H3 (15 kDa) can be analyzed with site specific assignments for multiple modifications. It also revealed K36 methylation in H3.3 was affected less by the overexpression of MMSET because of its higher methylation levels in control cells. The co-occurrence of acetylation with a minimum of three methyl groups in H3K9 and H3K27 suggested a hierarchy in the addition of certain modifications. Comparative analysis showed that high levels of MMSET in the myeloma-like cells drove the formation of hypermethyled proteoforms containing H3K36me2 co-existent with the repressive marks H3K9me2/3 and H3K27me2/3. Unique histone proteoforms with such "trivalent hypermethylation" (K9me2/3-K27me2/3-K36me2) were not discovered when H3.1 peptides were analyzed by Bottom-Up. Such disease-correlated proteoforms could link tightly to aberrant transcription programs driving cellular proliferation, and their precise description demonstrates that Top-Down mass spectrometry can now decode crosstalk involving up to three modified sites. PMID- 26272981 TI - cyNeo4j: connecting Neo4j and Cytoscape. AB - We developed cyNeo4j, a Cytoscape App to link Cytoscape and Neo4j databases to utilize the performance and storage capacities Neo4j offers. We implemented a Neo4j NetworkAnalyzer, ForceAtlas2 layout and Cypher component to demonstrate the possibilities a distributed setup of Cytoscape and Neo4j have. AVAILABILITY AND IMPLEMENTATION: The app is available from the Cytoscape App Store at http://apps.cytoscape.org/apps/cyneo4j, the Neo4j plugins at www.github.com/gsummer/cyneo4j-parent and the community and commercial editions of Neo4j can be found at http://www.neo4j.com. CONTACT: georg.summer@gmail.com. PMID- 26272980 TI - Proteomic Profiling of Detergent Resistant Membranes (Lipid Rafts) of Prostasomes. AB - Prostasomes are exosomes derived from prostate epithelial cells through exocytosis by multivesicular bodies. Prostasomes have a bilayered membrane and readily interact with sperm. The membrane lipid composition is unusual with a high contribution of sphingomyelin at the expense of phosphatidylcholine and saturated and monounsaturated fatty acids are dominant. Lipid rafts are liquid ordered domains that are more tightly packed than the surrounding nonraft phase of the bilayer. Lipid rafts are proposed to be highly dynamic, submicroscopic assemblies that float freely within the liquid disordered membrane bilayer and some proteins preferentially partition into the ordered raft domains. We asked the question whether lipid rafts do exist in prostasomes and, if so, which proteins might be associated with them. Prostasomes of density range 1.13 1.19g/ml were subjected to density gradient ultracentrifugation in sucrose fabricated by phosphate buffered saline (PBS) containing 1% Triton X-100 with capacity for banding at 1.10 g/ml, i.e. the classical density of lipid rafts. Prepared prostasomal lipid rafts (by gradient ultracentrifugation) were analyzed by mass spectrometry. The clearly visible band on top of 1.10g/ml sucrose in the Triton X-100 containing gradient was subjected to liquid chromatography-tandem MS and more than 370 lipid raft associated proteins were identified. Several of them were involved in intraluminal vesicle formation, e.g. tetraspanins, ESCRTs, and Ras-related proteins. This is the first comprehensive liquid chromatography tandem MS profiling of proteins in lipid rafts derived from exosomes. Data are available via ProteomeXchange with identifier PXD002163. PMID- 26272982 TI - OVA: integrating molecular and physical phenotype data from multiple biomedical domain ontologies with variant filtering for enhanced variant prioritization. AB - MOTIVATION: Exome sequencing has become a de facto standard method for Mendelian disease gene discovery in recent years, yet identifying disease-causing mutations among thousands of candidate variants remains a non-trivial task. RESULTS: Here we describe a new variant prioritization tool, OVA (ontology variant analysis), in which user-provided phenotypic information is exploited to infer deeper biological context. OVA combines a knowledge-based approach with a variant filtering framework. It reduces the number of candidate variants by considering genotype and predicted effect on protein sequence, and scores the remainder on biological relevance to the query phenotype.We take advantage of several ontologies in order to bridge knowledge across multiple biomedical domains and facilitate computational analysis of annotations pertaining to genes, diseases, phenotypes, tissues and pathways. In this way, OVA combines information regarding molecular and physical phenotypes and integrates both human and model organism data to effectively prioritize variants. By assessing performance on both known and novel disease mutations, we show that OVA performs biologically meaningful candidate variant prioritization and can be more accurate than another recently published candidate variant prioritization tool. AVAILABILITY AND IMPLEMENTATION: OVA is freely accessible at http://dna2.leeds.ac.uk:8080/OVA/index.jsp. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. CONTACT: umaan@leeds.ac.uk. PMID- 26272985 TI - Some advantages to having a parent with a disability. AB - Fertility specialists, adoption agents, judges and others sometimes take themselves to have a responsibility to fairly adjudicate conflicts that may arise between the procreative and parenting interests of people with disabilities and the interests that their children or potential children have to be nurtured, cared for and protected. An underlying assumption is that having a disability significantly diminishes a person's parenting abilities. My aim is to challenge the claim that having a disability tends to make someone a bad parent by arguing that the interests of prospective parents with disabilities and the interests of their children or potential children are often aligned and mutually supporting. PMID- 26272984 TI - motifbreakR: an R/Bioconductor package for predicting variant effects at transcription factor binding sites. AB - Functional annotation represents a key step toward the understanding and interpretation of germline and somatic variation as revealed by genome-wide association studies (GWAS) and The Cancer Genome Atlas (TCGA), respectively. GWAS have revealed numerous genetic risk variants residing in non-coding DNA associated with complex diseases. For sequences that lie within enhancers or promoters of transcription, it is not straightforward to assess the effects of variants on likely transcription factor binding sites. Consequently we introduce motifbreakR, which allows the biologist to judge whether the sequence surrounding a polymorphism or mutation is a good match, and how much information is gained or lost in one allele of the polymorphism or mutation relative to the other. MotifbreakR is flexible, giving a choice of algorithms for interrogation of genomes with motifs from many public sources that users can choose from. MotifbreakR can predict effects for novel or previously described variants in public databases, making it suitable for tasks beyond the scope of its original design. Lastly, it can be used to interrogate any genome curated within bioconductor. AVAILABILITY AND IMPLEMENTATION: https://github.com/Simon Coetzee/MotifBreakR, www.bioconductor.org. CONTACT: dennis.hazelett@cshs.org. PMID- 26272983 TI - Mutadelic: mutation analysis using description logic inferencing capabilities. AB - MOTIVATION: As next generation sequencing gains a foothold in clinical genetics, there is a need for annotation tools to characterize increasing amounts of patient variant data for identifying clinically relevant mutations. While existing informatics tools provide efficient bulk variant annotations, they often generate excess information that may limit their scalability. RESULTS: We propose an alternative solution based on description logic inferencing to generate workflows that produce only those annotations that will contribute to the interpretation of each variant. Workflows are dynamically generated using a novel abductive reasoning framework called a basic framework for abductive workflow generation (AbFab). Criteria for identifying disease-causing variants in Mendelian blood disorders were identified and implemented as AbFab services. A web application was built allowing users to run workflows generated from the criteria to analyze genomic variants. Significant variants are flagged and explanations provided for why they match or fail to match the criteria. AVAILABILITY AND IMPLEMENTATION: The Mutadelic web application is available for use at http://krauthammerlab.med.yale.edu/mutadelic. CONTACT: michael.krauthammer@yale.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26272989 TI - Education, Health, and the Default American Lifestyle. AB - Education has a large and increasing impact on health in America. This paper examines one reason why. Education gives individuals the ability to override the default American lifestyle. The default lifestyle has three elements: displacing human energy with mechanical energy, displacing household food production with industrial food production, and displacing health maintenance with medical dependency. Too little physical activity and too much food produce imperceptibly accumulating pathologies. The medical industry looks for products and services that promise to soften the consequences but do not eliminate the underlying pathologies. This "secondary prevention" creates pharmacologic accumulation: prolonging the use of medications, layering them, and accruing their side effects and interactions. Staying healthy depends on recognizing the risks of the default lifestyle. Overriding it requires insight, knowledge, critical analysis, long range strategic thinking, personal agency, and self-direction. Education develops that ability directly and indirectly, by way of creative work and a sense of controlling one's own life. PMID- 26272986 TI - End-of-life decisions for children under 1 year of age in the Netherlands: decreased frequency of administration of drugs to deliberately hasten death. AB - OBJECTIVE: To assess whether the frequency of end-of-life decisions for children under 1 year of age in the Netherlands has changed since ultrasound examination around 20 weeks of gestation became routine in 2007 and after a legal provision for deliberately ending the life of a newborn was set up that same year. METHODOLOGY: This was a recurrent nationwide cross-sectional study in the Netherlands. In 2010, a sample of death certificates from children under 1 year of age was derived from the central death registry. All 223 deaths that occurred in a 4-month study period were included. Physicians who had reported a non-sudden death (n=206) were sent a questionnaire on the end-of-life decisions made. 160 questionnaires were returned (response 78%). FINDINGS: In 2010, 63% of all deaths of children under 1 year of age were preceded by an end-of-life decision-a percentage comparable to other times when this study was conducted (1995, 2001, 2005). These end-of-life decisions were mainly decisions to withdraw or withhold potentially life-sustaining treatment. In 2010, the percentage of cases in which drugs were administered with the explicit intention to hasten death was 1%, while in 1995 and 2001, this was 9% and in 2005, this was 8%. DISCUSSION AND CONCLUSION: There has been a reduction of infant deaths that followed administration of drugs with the explicit intention to hasten death. One explanation for this reduction relates to the introduction of routine ultrasound examination around 20 weeks of gestation. In addition, the introduction of legal criteria and a review process for deliberately ending the life of a newborn may have left Dutch physicians with less room to hasten death. PMID- 26272990 TI - Acute Appendicitis and Pneumatosis in a Duplicated Appendix With Schistosoma Remnants. AB - Appendiceal pneumatosis is rare, reported either in the context of acute appendicitis or enterocolitis. Here, we report the case of an elderly adult in whom the acute appendicitis was associated with pneumatosis and occurred in the context of a malformed appendix with pathogenic organism remnants. A 72-year-old man presented with abdominal pain 3 weeks after posttraumatic dorsolumbar surgery. The computed tomography scan showed acute appendicitis and 2 diverticula. On microscopy, the appendix showed acute appendicitis along with a Cave-Wallbridge type A duplication. In addition, several optically clear spaces were observed in the entire appendiceal wall consistent with pneumatosis of the appendix. Focally, calcified structures suggesting pathogenic organisms such as Schistosoma were noted as well. In conclusion, we report a case of appendiceal pneumatosis occurring in the context of acute appendicitis in a duplicated appendix, with presence of calcified structures suggestive of pathogenic organisms. PMID- 26272991 TI - Palliative Medicine journal: What have we done, where should we be going and why? PMID- 26272988 TI - Marriage, Relationship Quality, and Sleep among U.S. Older Adults. AB - Sleep is a restorative behavior essential for health. Poor sleep has been linked to adverse health outcomes among older adults; however, we know little about the social processes that affect sleep. Using innovative actigraphy data from the National Social Life, Health, and Aging Project (N = 727), we considered the role of marriage, positive marital relationship support, and negative marital relationship strain on older adults' (ages 62-90) self-reported and actigraph measured sleep characteristics. We found that married older adults had better actigraph-estimated but not self-reported sleep characteristics than the unmarried. However, among the married, those who reported more negative aspects of their marital relationship reported more insomnia symptoms, with the association reduced when psychosocial characteristics were added to the model. The married who reported more positive aspects of their marital relationship showed better actigraph-estimated sleep characteristics; taking characteristics of the physical and mental health and home environment into account reduced this association. PMID- 26272992 TI - Application of the Vertex Exchange Method to estimate a semi-parametric mixture model for the MIC density of Escherichia coli isolates tested for susceptibility against ampicillin. AB - In the last decades, considerable attention has been paid to the collection of antimicrobial resistance data, with the aim of monitoring non-wild-type isolates. This monitoring is performed based on minimum inhibition concentration (MIC) values, which are collected through dilution experiments. We present a semi parametric mixture model to estimate the entire MIC density on the continuous scale. The parametric first component is extended with a non-parametric second component and a new back-fitting algorithm, based on the Vertex Exchange Method, is proposed. Our data example shows how to estimate the MIC density for Escherichia coli tested for ampicillin and how to use this estimate for model based classification. A simulation study was performed, showing the promising behavior of the new method, both in terms of density estimation as well as classification. PMID- 26272993 TI - Causal mediation analysis for longitudinal data with exogenous exposure. AB - Mediation analysis is a valuable approach to examine pathways in epidemiological research. Prospective cohort studies are often conducted to study biological mechanisms and often collect longitudinal measurements on each participant. Mediation formulae for longitudinal data have been developed. Here, we formalize the natural direct and indirect effects using a causal framework with potential outcomes that allows for an interaction between the exposure and the mediator. To allow different types of longitudinal measures of the mediator and outcome, we assume two generalized mixed-effects models for both the mediator and the outcome. The model for the mediator has subject-specific random intercepts and random exposure slopes for each cluster, and the outcome model has random intercepts and random slopes for the exposure, the mediator, and their interaction. We also expand our approach to settings with multiple mediators and derive the mediated effects, jointly through all mediators. Our method requires the absence of time-varying confounding with respect to the exposure and the mediator. This assumption is achieved in settings with exogenous exposure and mediator, especially when exposure and mediator are not affected by variables measured at earlier time points. We apply the methodology to data from the Normative Aging Study and estimate the direct and indirect effects, via DNA methylation, of air pollution, and temperature on intercellular adhesion molecule 1 (ICAM-1) protein levels. Our results suggest that air pollution and temperature have a direct effect on ICAM-1 protein levels (i.e. not through a change in ICAM 1 DNA methylation) and that temperature has an indirect effect via a change in ICAM-1 DNA methylation. PMID- 26272995 TI - Ellsworth C. Dougherty: A Pioneer in the Selection of Caenorhabditis elegans as a Model Organism. AB - Ellsworth Dougherty (1921-1965) was a man of impressive intellectual dimensions and interests; in a relatively short career he contributed enormously as researcher and scholar to the biological knowledge base for selection of Caenorhabditis elegans as a model organism in neurobiology, genetics, and molecular biology. He helped guide the choice of strains that were eventually used, and, in particular, he developed the methodology and understanding for the nutrition and axenic culture of nematodes and other organisms. Dougherty insisted upon a concise terminology for culture techniques and coined descriptive neologisms that were justified by their linguistic roots. Among other contributions, he refined the classification system for the Protista. PMID- 26272994 TI - Methods that remove batch effects while retaining group differences may lead to exaggerated confidence in downstream analyses. AB - Removal of, or adjustment for, batch effects or center differences is generally required when such effects are present in data. In particular, when preparing microarray gene expression data from multiple cohorts, array platforms, or batches for later analyses, batch effects can have confounding effects, inducing spurious differences between study groups. Many methods and tools exist for removing batch effects from data. However, when study groups are not evenly distributed across batches, actual group differences may induce apparent batch differences, in which case batch adjustments may bias, usually deflate, group differences. Some tools therefore have the option of preserving the difference between study groups, e.g. using a two-way ANOVA model to simultaneously estimate both group and batch effects. Unfortunately, this approach may systematically induce incorrect group differences in downstream analyses when groups are distributed between the batches in an unbalanced manner. The scientific community seems to be largely unaware of how this approach may lead to false discoveries. PMID- 26273000 TI - Strong opposition to closure of surveillance centre. PMID- 26272998 TI - Corrigendum. PMID- 26273001 TI - New priorities set out in dairy cow welfare strategy. PMID- 26272996 TI - Programmed Cell Death Initiation and Execution in Budding Yeast. AB - Apoptosis or programmed cell death (PCD) was initially described in metazoans as a genetically controlled process leading to intracellular breakdown and engulfment by a neighboring cell . This process was distinguished from other forms of cell death like necrosis by maintenance of plasma membrane integrity prior to engulfment and the well-defined genetic system controlling this process. Apoptosis was originally described as a mechanism to reshape tissues during development. Given this context, the assumption was made that this process would not be found in simpler eukaryotes such as budding yeast. Although basic components of the apoptotic pathway were identified in yeast, initial observations suggested that it was devoid of prosurvival and prodeath regulatory proteins identified in mammalian cells. However, as apoptosis became extensively linked to the elimination of damaged cells, key PCD regulatory proteins were identified in yeast that play similar roles in mammals. This review highlights recent discoveries that have permitted information regarding PCD regulation in yeast to now inform experiments in animals. PMID- 26272997 TI - Freedom and Responsibility in Synthetic Genomics: The Synthetic Yeast Project. AB - First introduced in 2011, the Synthetic Yeast Genome (Sc2.0) PROJECT is a large international synthetic genomics project that will culminate in the first eukaryotic cell (Saccharomyces cerevisiae) with a fully synthetic genome. With collaborators from across the globe and from a range of institutions spanning from do-it-yourself biology (DIYbio) to commercial enterprises, it is important that all scientists working on this project are cognizant of the ethical and policy issues associated with this field of research and operate under a common set of principles. In this commentary, we survey the current ethics and regulatory landscape of synthetic biology and present the Sc2.0 Statement of Ethics and Governance to which all members of the project adhere. This statement focuses on four aspects of the Sc2.0 PROJECT: societal benefit, intellectual property, safety, and self-governance. We propose that such project-level agreements are an important, valuable, and flexible model of self-regulation for similar global, large-scale synthetic biology projects in order to maximize the benefits and minimize potential harms. PMID- 26273002 TI - Revised guidelines on responsible use of antimicrobials in cattle production. PMID- 26273004 TI - Focusing on animal welfare education. PMID- 26273003 TI - FSA seeks information on edible insect consumption. PMID- 26273005 TI - Success in statutory exam celebrated. PMID- 26273006 TI - Dolly stars in festival exhibition. PMID- 26273007 TI - Synergies and challenges in tackling disease issues and emergency events. PMID- 26273008 TI - Antibiotics: expect to use less, more responsibly. PMID- 26273010 TI - Is EBVM ethical? PMID- 26273011 TI - Controlling porcine epidemic diarrhoea. PMID- 26273009 TI - Equine metabolic syndrome. AB - Laminitis is one of the most common and frustrating clinical presentations in equine practice. While the principles of treatment for laminitis have not changed for several decades, there have been some important paradigm shifts in our understanding of laminitis. Most importantly, it is essential to consider laminitis as a clinical sign of disease and not as a disease in its own right. Once this shift in thinking has occurred, it is logical to then question what disease caused the laminitis. More than 90 per cent of horses presented with laminitis as their primary clinical sign will have developed it as a consequence of endocrine disease; most commonly equine metabolic syndrome (EMS). Given the fact that many horses will have painful protracted and/or chronic recurrent disease, a good understanding of the predisposing factors and how to diagnose and manage them is crucial. Current evidence suggests that early diagnosis and effective management of EMS should be a key aim for practising veterinary surgeons to prevent the devastating consequences of laminitis. This review will focus on EMS, its diagnosis and management. PMID- 26273012 TI - Forensic investigation of drowning. PMID- 26273013 TI - Developing a 'bedside' test for cervical neck pain in Cavalier King Charles spaniels with syringomyelia. PMID- 26273014 TI - Achieving specialist status. PMID- 26273015 TI - The safety and tolerability of adenosine as a pharmacological stressor in stress perfusion cardiac magnetic resonance imaging in the Chinese population. AB - OBJECTIVE: To investigate the safety profile and effectiveness of adenosine as a pharmacological stressor in patients with known or suspected coronary artery disease who underwent cardiac magnetic resonance imaging perfusion study. SETTING: Regional hospital, Hong Kong. PATIENTS: All patients who underwent adenosine stress cardiac magnetic resonance imaging from May 2013 to August 2013 were prospectively interviewed during the scan. MAIN OUTCOME MEASURES: Common side-effects of adenosine as well as any other discomfort experienced during the scan were recorded. Haemodynamic changes including systolic and diastolic blood pressure and pulse rate before and during adenosine administration were also recorded. RESULTS: There were 98 consecutive patients with a mean (+/- standard deviation) age of 64.0 +/- 11.4 years (range, 10-83 years) and mean body weight of 67.5 +/- 12.0 kg. Male-to-female ratio was 2.5:1. Of the 98 patients interviewed, 62 (63.3%) experienced one or more adenosine-associated adverse effects. Chest discomfort was most frequently experienced (48.0%), followed by dyspnoea (29.6%) and headache (20.4%). No life-threatening event occurred. Following adenosine administration, a significant rise in pulse rate (75.1 +/- 14.3 vs 93.2 +/- 14.7 beats/min; P<0.01) and a significant drop in diastolic blood pressure (75.1 +/- 13.3 vs 68.0 +/- 13.9 mm Hg; P<0.01) were noted. There was a general decrease in systolic blood pressure, although no statistically significant difference was observed (144.9 +/- 17.6 vs 143.1 +/- 21.4 mm Hg; P=0.18). CONCLUSION: Adenosine stress cardiac magnetic resonance perfusion study is safe and well tolerated in clinical practice. PMID- 26273016 TI - Clinical value of transforaminal epidural steroid injection in lumbar radiculopathy. AB - OBJECTIVES: To identify the diagnostic, therapeutic, and prognostic values of transforaminal epidural steroid injection as interventional rehabilitation for lumbar radiculopathy. SETTING: Regional hospital, Hong Kong. PATIENTS: A total of 232 Chinese patients with lumbar radiculopathy attributed to disc herniation or spinal stenosis received transforaminal epidural steroid injection between 1 January 2007 and 31 December 2011. INTERVENTIONS: Transforaminal epidural steroid injection. MAIN OUTCOME MEASURES: Patients' immediate response, response duration, proportion of patients requiring surgery, and risk factors affecting the responses to transforaminal epidural steroid injection for lumbar radiculopathy. RESULTS: Of the 232 patients, 218 (94.0%) had a single level of radiculopathy and 14 (6.0%) had multiple levels. L5 was the most commonly affected level. The immediate response rate to transforaminal epidural steroid injection was 80.2% in 186 patients with clinically diagnosed lumbar radiculopathy and magnetic resonance imaging of the lumbar spine suggesting nerve root compression. Of patients with single-level radiculopathy and multiple-level radiculopathy, 175 (80.3%) and 11 (78.6%) expressed an immediate response to transforaminal epidural steroid injection, respectively. The analgesic effect lasted for 1 to <3 weeks in 35 (15.1%) patients, for 3 to 12 weeks in 37 (15.9%) patients, and for more than 12 weeks in 92 (39.7%) patients. Of the 232 patients, 106 (45.7%) were offered surgery, with 65 (61.3%) undergoing operation, and with 42 (64.6%) requiring spinal fusion in addition to decompression surgery. Symptom chronicity was associated with poor immediate response to transforaminal epidural steroid injection, but not with duration of pain reduction. Poor response to transforaminal epidural steroid injection was not associated with a preceding industrial injury. CONCLUSIONS: The immediate response to transforaminal epidural steroid injection was approximately 80%. Transforaminal epidural steroid injection is a useful diagnostic, prognostic, and short-term therapeutic tool for lumbar radiculopathy. Although transforaminal epidural steroid injection cannot alter the need for surgery in the long term, it is a reasonably safe procedure to provide short-term pain relief and as a preoperative assessment tool. PMID- 26273017 TI - Waldenstrom's macroglobulinemia associated with Hodgkin's lymphoma: a case report. AB - Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) is a low grade B-cell non-Hodgkin's lymphoma with an indolent clinical course. Higher grade non-Hodgkin lymphoma (NHL) and therapy-related myelodysplasia/acute leukemia (t-MDS/AML) have been reported in patients with WM/LPL in previous studies. However, only two cases with WM/LPL were reported to develop to Hodgkin lymphoma (HL). Here, we report the first case of WM/LPL who developed classical HL simultaneously 3 years after initial nucleoside analog-based chemotherapy. PMID- 26273018 TI - Differential mRNA expression profiling of oral squamous cell carcinoma by high throughput RNA sequencing. AB - Differentially expressed genes are thought to regulate the development and progression of oral squamous cell carcinomas (OSCC). The purpose of this study was to screen differentially expressed mRNAs in OSCC and matched paraneoplastic normal tissues, and to explore the intrinsic mechanism of OSCC development and progression. We obtained the differentially expressed mRNA expression profiles in 10 pairs of fresh-frozen OSCC tissue specimens and matched paraneoplastic normal tissue specimens by high-throughput RNA sequencing. By using Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, the functional significance of the differentially expressed genes were analyzed. We identified 1,120 significantly up-regulated mRNAs and 178 significantly down-regulated mRNAs in OSCC, compared to normal tissue. The differentially expressed mRNAs were involved in 20 biological processes and 68 signal pathways. Compared to adjacent normal tissue, the expression of MAGEA11 was up-regulated; TCHH was down-regulated. These findings were verified by real time PCR. These differentially expressed mRNAs may function as oncogenes or tumor suppressors in the development and progression of OSCC. This study provides novel insights into OSCC. However, further work is needed to determine if these differentially expressed mRNAs have potential roles as diagnostic biomarkers and candidate therapeutic targets for OSCC. PMID- 26273020 TI - Long-term Consequences of Noninjurious and Injurious Falls on Well-being in Older Women. AB - BACKGROUND: The physical and mental health consequences of falls are known to influence well-being in the short term. The aim was to investigate the long-term consequences of noninjurious and injurious falls on well-being in older women over 12 years. METHODS: A total of 10,277 participants (aged 73-78 years, 98.8% community-dwelling) returned the 1999 survey of the Australian Longitudinal Study on Women's Health. Follow-up surveys were completed at 3-year intervals. Surveys included questions about falls and related injuries in the past year. Scores on the health-related quality of life Short Form-36 subscales (range 0-100) were used to compare well-being between noninjurious fallers, injurious fallers, and nonfallers using linear mixed modeling with adjustment for confounders. Scores in the years before and after the first fall since enrolment were graphically depicted with time relative to the first fall since enrolment. For this purpose, nonfallers were matched with noninjurious and injurious fallers based on pattern of surveys returned, chronic conditions, and age to assign them a fictitious "time-of-first-fall." RESULTS: Over 12 years, there were 22.5% noninjurious fallers, 30.1% injurious fallers, and 47.5% nonfallers. Compared with nonfallers, noninjurious and injurious fallers scored significantly lower on six and seven of the eight domains at the time of the reported fall, respectively. Significant differences were apparent 12 years before the injurious fall for the subscales role physical, bodily pain, and general health. A drop in scores after the reported injurious fall was seen for role physical, bodily pain, and social functioning. CONCLUSIONS: Among older women, a gap in well-being emerges years before the first reported fall, which may be driven by underlying risk factors rather than the fall itself. PMID- 26273019 TI - Are Performance Measures Necessary to Predict Loss of Independence in Elderly People? AB - BACKGROUND: The frailty phenotype (FP) proposed by Fried and colleagues (Fried LP, Tangen CM, Walston J, et al.; Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146-M156.) requires the administration of performance tests (gait speed, handgrip strength) not always feasible in routine clinical practice. Furthermore, the discriminative capacity of the instrument has been rarely investigated. Aim of this study was to evaluate the discriminative capacity of the FP and compare it with a modified version including only anamnestic information. METHODS: Data are from 890 participants of the InCHIANTI study without impairment in activities of daily living (ADL) at baseline (mean age 74 years, women 55%). Frailty was defined by (a) the presence of >= 3 criteria of the FP, and (b) having >= 2 criteria of an anamnestic FP (AFP), not including gait speed and handgrip strength. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) were used to evaluate the discriminative capacity of both definitions for incident disability (ie, loss of at least one ADL), incidence of "accelerated" disability (loss of >2 ADL) over a 6-year follow-up, and 5-years mortality. RESULTS: FP and AFP yielded a frailty prevalence of 6.4% and 6.5%, respectively; only 32 patients were considered frail by both indices (kappa: .53). For incident disability, FP showed sensitivity = .194, specificity = .963, PPV = .400, and NPV = .903. Similarly, AFP had sensitivity = .129, specificity = .949, PPV = .245, and NPV = .894. Consistent results were found for accelerated disability and mortality. CONCLUSIONS: In our sample, both FP and AFP showed low sensitivity in identifying older people who would die or develop disability, but they could well discriminate people who would not experience adverse outcomes. PMID- 26273021 TI - Evaluation of Cutpoints for Low Lean Mass and Slow Gait Speed in Predicting Death in the National Health and Nutrition Examination Survey 1999-2004. AB - BACKGROUND: Sarcopenia is commonly defined as loss of muscle mass with limited muscle function or strength. Different cutpoints of low lean mass and slow gait speed have been proposed by different professional working groups. We compared the performance of different cutpoints of low lean mass and slow gait speed in predicting death. METHODS: We analyzed data of participants aged 65 years or older from the continuous National Health and Nutrition Examination Survey 1999 2004 (N = 2,841), and the subsequent follow-up data on mortality up to December 31, 2006. For low lean mass, cutpoints based on appendicular lean mass (ALM) alone, ALM adjusted for body mass index (ALMBMI), and ALM adjusted for height squared (ALMH2) were evaluated. For slow gait speed, the cutpoints based on 0.8 and 1.0 m/s were evaluated. A Cox-proportional hazard regression model with adjustment for multiple confounding factors was used for the association analyses. RESULTS: For low lean mass, the cutpoints based on ALMBMI (<0.512 in women and <0.789 in men) showed the most significant association and highest hazard ratio with death (hazard ratio = 1.72; 95% CI: 1.28-2.29). For slow gait speed, all cutpoints tested showed significant association with death in the full model (p < .001), while the cutpoint 0.8 m/s showed the highest hazard ratio (2.32; 95% CI: 1.58-3.39). CONCLUSIONS: Low lean mass defined by ALMBMI showed the strongest association with death; while slow gait speed showed significant association with death, with the strongest association being observed for the cutpoint of 0.8 m/s. Further studies validating the cutpoints are warranted before using them in clinical settings. PMID- 26273022 TI - Frailty Index and Incident Mortality, Hospitalization, and Institutionalization in Alzheimer's Disease: Data From the ICTUS Study. AB - BACKGROUND: The identification of an objective evaluation of frailty capable of predicting adverse outcomes in Alzheimer's disease is increasingly discussed. The purpose of this study was to investigate whether the Frailty Index (FI) predicts hospitalization, institutionalization, and mortality in Alzheimer's disease patients. METHODS: A prospective multicenter cohort study (follow-up = 2 years) that included 1,191 participants with Alzheimer's disease was carried out. The outcomes of interest were incident hospitalization, institutionalization, and mortality. The FI was calculated as the ratio of actual to thirty potential deficits, that is, deficits presented by the participant divided by 30. Severity of dementia was assessed using the Clinical Dementia Rating score. Cox proportional hazard models were performed. RESULTS: Mean age of the study sample was 76.2 (SD = 7.6) years. A quadratic relationship of the FI with age was reported at baseline (R (2) = .045, p < .001). The FI showed a statistically significant association with mortality (age- and gender-adjusted hazard ratio [HR] = 1.019, 95% confidence interval [CI] = 1.002-1.037, p = .031) and hospitalization (age- and gender-adjusted HR = 1.017, 95% CI = 1.006-1.029, p = .004) and a borderline significance with institutionalization. When the Clinical Dementia Rating score was simultaneously included in the age- and gender-adjusted models, the FI confirmed its predictive capacity for hospitalization (HR = 1.019, 95% CI = 1.006-1.032, p = .004), whereas the Clinical Dementia Rating score was the strongest predictor for mortality (HR = 1.922, 95% CI = 1.256-2.941, p = .003) and institutionalization (HR = 1.955, 95%CI = 1.427-2.679, p < .001). CONCLUSIONS: The FI is a robust predictor of adverse outcomes even after the stage of the underlying dementia is considered. Future work should evaluate the clinical implementation of the FI in the assessment of demented individuals in order to improve the personalization of care. PMID- 26273026 TI - Energy - A Hallmark of Physical Function. PMID- 26273024 TI - Independent Associations Between Sedentary Behaviors and Mental, Cognitive, Physical, and Functional Health Among Older Adults in Retirement Communities. AB - BACKGROUND: We examined the relationships between objective and self-reported sedentary time and health indicators among older adults residing in retirement communities. METHODS: Our cross-sectional analysis used data from 307 participants who completed baseline measurements of a physical activity trial in 11 retirement communities in San Diego County. Sedentary time was objectively measured with devices (accelerometers) and using self-reports. Outcomes assessed included emotional and cognitive health, physical function, and physical health (eg, blood pressure). Linear mixed-effects models examined associations between sedentary behavior and outcomes adjusting for demographics and accelerometer physical activity. RESULTS: Higher device-measured sedentary time was associated with worse objective physical function (Short Physical Performance Battery, balance task scores, 400-m walk time, chair stand time, gait speed), self reported physical function, and fear of falling but with less sleep disturbance (all ps < .05). TV viewing was positively related to 400-m walk time (p < .05). Self-reported sedentary behavior was related to better performance on one cognitive task (trails A; p < .05). CONCLUSIONS: Sedentary time was mostly related to poorer physical function independently of moderate-to-vigorous physical activity and may be a modifiable behavior target in interventions aiming to improve physical function in older adults. Few associations were observed with self-reported sedentary behavior measures. PMID- 26273027 TI - "Old Oxen Cannot Plow": Stereotype Themes of Older Adults in Turkish Folklore. AB - PURPOSE OF THE STUDY: Although much research has established the nature of attitudes and stereotypes toward older adults, there are conflicting explanations for the root cause of ageism, including the sociocultural view and interpersonal views, that age bias against older adults is uniquely a product of modernity and occurs through social interactions, and the evolutionary view and intraindividual views, that age bias against older adults is rooted in our naturally occurring and individually held fear of death. We make initial investigations into resolving this conflict, by analyzing literature from a society predating the Industrial Revolution, the society of Ottoman Turks. DESIGN AND METHODS: Using Grounded Theory, we analyzed 1,555 Turkish fairy tales of the most well-known older adult in Turkish folklore, Nasreddin Hoca, for stereotype themes of older adults. Using the same method, we then analyzed 22,000+ Turkish sayings and proverbs for the same themes. RESULTS: Results indicated older adults to be viewed both positively and negatively. Positive stereotypes included wisdom, warmth, deserving of respect, and retirement. Negative stereotypes included incompetence, inadaptability, and frailty/nearing of death. Older females were viewed more negatively relative to older males. IMPLICATIONS: Results indicated views of older adults to parallel those found in contemporary research. Results have implications for the design of interventions to reduce ageism and on the cross-cultural generalizability of age-based stereotypes. PMID- 26273025 TI - Depressive Trajectories and Risk of Disability and Mortality in Older Adults: Longitudinal Findings From the Health, Aging, and Body Composition Study. AB - BACKGROUND: Depression and disability are closely linked. Less is known regarding clinical and subclinical depressive symptoms over time and risk of disability and mortality. METHODS: Responses to the Center for Epidemiologic Studies Short Depression scale (CES-D10) were assessed over a 4-year period in men (n = 1032) and women (n = 1070) aged 70-79 years initially free from disability. Depressive symptom trajectories were defined with group-based models. Disability (2 consecutive reports of severe difficulty walking one-quarter mile or climbing 10 steps) and mortality were determined for 9 subsequent years. Hazard ratios (HRs) were estimated using Cox proportional hazards adjusted for covariates. RESULTS: Three trajectories were identified: persistently nondepressed (54% of men, 54% of women, mean baseline CES-D10: 1.16 and 1.46), mildly depressed and increasing (40% of men, 38% of women, mean baseline CES-D10: 3.60 and 4.35), and depressed and increasing (6% of men, 8% of women, mean baseline CES-D10: 7.44 and 9.61). Disability and mortality rates per 1,000 person years were 41.4 and 60.3 in men and 45.8 and 41.9 in women. Relative to nondepressed, men in the mildly depressed (HR = 1.45, 95% confidence interval [CI] 1.11-1.89) and depressed trajectories (HR = 2.12, 95% CI 1.33-3.38) had increased disability; women in the depressed trajectory had increased disability (HR = 2.02, 95% CI 1.37-2.96). Men in the mildly depressed (HR = 1.24, 95% CI 1.01-1.52) and depressed trajectories (HR = 1.63, 95% CI 1.10-2.41) had elevated mortality risk; women exhibited no mortality risk. CONCLUSIONS: Trajectories of depressive symptoms without recovery may predict disability and mortality in apparently healthy older populations, thus underscoring the importance of monitoring depressive symptoms in geriatric care. PMID- 26273030 TI - SCIENCE DIPLOMACY. Iran's atomic czar describes the art of the deal. PMID- 26273028 TI - Science, all inclusive. PMID- 26273031 TI - POLAR SCIENCE. Report sets new goals for U.S. Antarctic Program. PMID- 26273033 TI - MARINE GEOLOGY. Russian claim heats up battle to control Arctic sea floor. PMID- 26273023 TI - Increased Adipocyte Area in Injured Muscle With Aging and Impaired Remodeling in Female Mice. AB - We demonstrated that young male and female mice similarly regenerated injured skeletal muscle; however, female mice transiently increased adipocyte area within regenerated muscle in a sex hormone-dependent manner. We extended these observations to investigate the effect of aging and sex on sarcopenia and muscle regeneration. Cardiotoxin injury to the tibialis anterior muscle of young, middle, and old-aged C57Bl/6J male and female mice was used to measure regenerated myofiber cross-sectional area (CSA), adipocyte area, residual necrosis, and inflammatory cell recruitment. Baseline (uninjured) myofiber CSA was decreased in old mice of both sexes compared to young and middle-aged mice. Regenerated CSA was similar in male mice in all age groups until baseline CSA was attained but decreased in middle and old age female mice compared to young females. Furthermore, adipocyte area within regenerated muscle was transiently increased in young females compared to young males and these sex-dependent increases persisted in middle and old age female mice and were associated with increased Pparg Young female mice had more pro-inflammatory monocytes/macrophages in regenerating muscle than young male mice and increased Sca-1(+)CD45(-)cells. In conclusion, sex and age influence pro-inflammatory cell recruitment, muscle regeneration, and adipocyte area following skeletal muscle injury. PMID- 26273032 TI - SYNTHETIC BIOLOGY. Modified yeast produce opiates from sugar. PMID- 26273034 TI - ANTHROPOLOGY. Mashco Piro tribe emerges from isolation in Peru. PMID- 26273035 TI - The littlest farmhands. PMID- 26273037 TI - Satellites provide the big picture. PMID- 26273038 TI - Time for in situ renaissance. PMID- 26273039 TI - GEOPHYSICS. How mountains get made. PMID- 26273040 TI - DEVELOPMENT. Marmoset kids actually listen. PMID- 26273041 TI - NEUROSCIENCE. Astrocytes tell neurons when to listen up. PMID- 26273042 TI - CLIMATE CHANGE. Has there been a hiatus? PMID- 26273043 TI - VACCINES. Ebola virus vaccines--preparing for the unexpected. PMID- 26273044 TI - CANCER. Tumor angiogenesis, from foe to friend. PMID- 26273045 TI - QUANTUM OPTICS. The on-ramp to the all-optical quantum information processing highway. PMID- 26273046 TI - Parks for science, science for parks. PMID- 26273047 TI - Disaster response: Volunteers, unite! PMID- 26273049 TI - PALEOCEANOGRAPHY. A warm and poorly ventilated deep Arctic Mediterranean during the last glacial period. AB - Changes in the formation of dense water in the Arctic Ocean and Nordic Seas [the "Arctic Mediterranean" (AM)] probably contributed to the altered climate of the last glacial period. We examined past changes in AM circulation by reconstructing radiocarbon ventilation ages of the deep Nordic Seas over the past 30,000 years. Our results show that the glacial deep AM was extremely poorly ventilated (ventilation ages of up to 10,000 years). Subsequent episodic overflow of aged water into the mid-depth North Atlantic occurred during deglaciation. Proxy data also suggest that the deep glacial AM was ~2 degrees to 3 degrees C warmer than modern temperatures; deglacial mixing of the deep AM with the upper ocean thus potentially contributed to the melting of sea ice, icebergs, and terminal ice sheet margins. PMID- 26273050 TI - MAGNETISM. Imaging and control of ferromagnetism in LaMnO3/SrTiO3 heterostructures. AB - Oxide heterostructures often exhibit unusual physical properties that are absent in the constituent bulk materials. Here, we report an atomically sharp transition to a ferromagnetic phase when polar antiferromagnetic LaMnO3 (001) films are grown on SrTiO3 substrates. For a thickness of six unit cells or more, the LaMnO3 film abruptly becomes ferromagnetic over its entire area, which is visualized by scanning superconducting quantum interference device microscopy. The transition is explained in terms of electronic reconstruction originating from the polar nature of the LaMnO3 (001) films. Our results demonstrate that functionalities can be engineered in oxide films that are only a few atomic layers thick. PMID- 26273051 TI - GEOPHYSICS. Layered deformation in the Taiwan orogen. AB - The underthrusting of continental crust during mountain building is an issue of debate for orogens at convergent continental margins. We report three-dimensional seismic anisotropic tomography of Taiwan that shows a nearly 90 degrees rotation of anisotropic fabrics across a 10- to 20-kilometer depth, consistent with the presence of two layers of deformation. The upper crust is dominated by collision related compressional deformation, whereas the lower crust of Taiwan, mostly the crust of the subducted Eurasian plate, is dominated by convergence-parallel shear deformation. We interpret this lower crustal shearing as driven by the continuous sinking of the Eurasian mantle lithosphere when the surface of the subducted plate is coupled with the orogen. The two-layer deformation clearly defines the role of subduction in the formation of the Taiwan mountain belt. PMID- 26273052 TI - 2D MATERIALS. Observation of tunable band gap and anisotropic Dirac semimetal state in black phosphorus. AB - Black phosphorus consists of stacked layers of phosphorene, a two-dimensional semiconductor with promising device characteristics. We report the realization of a widely tunable band gap in few-layer black phosphorus doped with potassium using an in situ surface doping technique. Through band structure measurements and calculations, we demonstrate that a vertical electric field from dopants modulates the band gap, owing to the giant Stark effect, and tunes the material from a moderate-gap semiconductor to a band-inverted semimetal. At the critical field of this band inversion, the material becomes a Dirac semimetal with anisotropic dispersion, linear in armchair and quadratic in zigzag directions. The tunable band structure of black phosphorus may allow great flexibility in design and optimization of electronic and optoelectronic devices. PMID- 26273053 TI - APPLIED OPTICS. Voltage-tunable circular photogalvanic effect in silicon nanowires. AB - Electronic bands in crystals can support nontrivial topological textures arising from spin-orbit interactions, but purely orbital mechanisms can realize closely related dynamics without breaking spin degeneracies, opening up applications in materials containing only light elements. One such application is the circular photogalvanic effect (CPGE), which is the generation of photocurrents whose magnitude and polarity depend on the chirality of optical excitation. We show that the CPGE can arise from interband transitions at the metal contacts to silicon nanowires, where inversion symmetry is locally broken by an electric field. Bias voltage that modulates this field further controls the sign and magnitude of the CPGE. The generation of chirality-dependent photocurrents in silicon with a purely orbital-based mechanism will enable new functionalities in silicon that can be integrated with conventional electronics. PMID- 26273054 TI - Circuit-specific signaling in astrocyte-neuron networks in basal ganglia pathways. AB - Astrocytes are important regulatory elements in brain function. They respond to neurotransmitters and release gliotransmitters that modulate synaptic transmission. However, the cell- and synapse-specificity of the functional relationship between astrocytes and neurons in certain brain circuits remains unknown. In the dorsal striatum, which mainly comprises two intermingled subtypes (striatonigral and striatopallidal) of medium spiny neurons (MSNs) and synapses belonging to two neural circuits (the direct and indirect pathways of the basal ganglia), subpopulations of astrocytes selectively responded to specific MSN subtype activity. These subpopulations of astrocytes released glutamate that selectively activated N-methyl-d-aspartate receptors in homotypic, but not heterotypic, MSNs. Likewise, astrocyte subpopulations selectively regulated homotypic synapses through metabotropic glutamate receptor activation. Therefore, bidirectional astrocyte-neuron signaling selectively occurs between specific subpopulations of astrocytes, neurons, and synapses. PMID- 26273055 TI - LANGUAGE DEVELOPMENT. The developmental dynamics of marmoset monkey vocal production. AB - Human vocal development occurs through two parallel interactive processes that transform infant cries into more mature vocalizations, such as cooing sounds and babbling. First, natural categories of sounds change as the vocal apparatus matures. Second, parental vocal feedback sensitizes infants to certain features of those sounds, and the sounds are modified accordingly. Paradoxically, our closest living ancestors, nonhuman primates, are thought to undergo few or no production-related acoustic changes during development, and any such changes are thought to be impervious to social feedback. Using early and dense sampling, quantitative tracking of acoustic changes, and biomechanical modeling, we showed that vocalizations in infant marmoset monkeys undergo dramatic changes that cannot be solely attributed to simple consequences of growth. Using parental interaction experiments, we found that contingent parental feedback influences the rate of vocal development. These findings overturn decades-old ideas about primate vocalizations and show that marmoset monkeys are a compelling model system for early vocal development in humans. PMID- 26273058 TI - Creating a research brand. PMID- 26273057 TI - EVOLUTION. Fruit flies diversify their offspring in response to parasite infection. AB - The evolution of sexual reproduction is often explained by Red Queen dynamics: Organisms must continually evolve to maintain fitness relative to interacting organisms, such as parasites. Recombination accompanies sexual reproduction and helps diversify an organism's offspring, so that parasites cannot exploit static host genotypes. Here we show that Drosophila melanogaster plastically increases the production of recombinant offspring after infection. The response is consistent across genetic backgrounds, developmental stages, and parasite types but is not induced after sterile wounding. Furthermore, the response appears to be driven by transmission distortion rather than increased recombination. Our study extends the Red Queen model to include the increased production of recombinant offspring and uncovers a remarkable ability of hosts to actively distort their recombination fraction in rapid response to environmental cues. PMID- 26273056 TI - DNA REPAIR. Mus81 and converging forks limit the mutagenicity of replication fork breakage. AB - Most spontaneous DNA double-strand breaks (DSBs) result from replication-fork breakage. Break-induced replication (BIR), a genome rearrangement-prone repair mechanism that requires the Pol32/POLD3 subunit of eukaryotic DNA Poldelta, was proposed to repair broken forks, but how genome destabilization is avoided was unknown. We show that broken fork repair initially uses error-prone Pol32 dependent synthesis, but that mutagenic synthesis is limited to within a few kilobases from the break by Mus81 endonuclease and a converging fork. Mus81 suppresses template switches between both homologous sequences and diverged human Alu repetitive elements, highlighting its importance for stability of highly repetitive genomes. We propose that lack of a timely converging fork or Mus81 may propel genome instability observed in cancer. PMID- 26273059 TI - DEVICE TECHNOLOGY. Nanomaterials in transistors: From high-performance to thin film applications. AB - For more than 50 years, silicon transistors have been continuously shrunk to meet the projections of Moore's law but are now reaching fundamental limits on speed and power use. With these limits at hand, nanomaterials offer great promise for improving transistor performance and adding new applications through the coming decades. With different transistors needed in everything from high-performance servers to thin-film display backplanes, it is important to understand the targeted application needs when considering new material options. Here the distinction between high-performance and thin-film transistors is reviewed, along with the benefits and challenges to using nanomaterials in such transistors. In particular, progress on carbon nanotubes, as well as graphene and related materials (including transition metal dichalcogenides and X-enes), outlines the advances and further research needed to enable their use in transistors for high performance computing, thin films, or completely new technologies such as flexible and transparent devices. PMID- 26273060 TI - Genomic patterns associated with hypoplastic compared to hyperplastic myelodysplastic syndromes. PMID- 26273062 TI - Agenda setting for maternal survival: the power of global health networks and norms. AB - Nearly 300,000 women--almost all poor women in low-income countries--died from pregnancy-related complications in 2010. This represents a decline since the 1980s, when an estimated half million women died each year, but is still far higher than the aims set in the United Nations Millennium Development Goals (MDGs) at the turn of the century. The 1970s, 1980s and 1990 s witnessed a shift from near complete neglect of the issue to emergence of a network of individuals and organizations with a shared concern for reducing maternal deaths and growth in the number of organizations and governments with maternal health strategies and programmes. Maternal health experienced a marked change in agenda status in the 2000s, attracting significantly higher level attention (e.g. from world leaders) and greater resource commitments (e.g. as one issue addressed by US$40 billion in pledges to the 2010 Global Strategy for Women's and Children's Health) than ever before. Several differences between network and actor features, issue characteristics and the policy environment pre- and post-2000 help to explain the change in agenda status for global maternal mortality reduction. Significantly, a strong poverty reduction norm emerged at the turn of the century; represented by the United Nations MDGs framework, the norm set unusually strong expectations for international development actors to advance included issues. As the norm grew, it drew policy attention to the maternal health goal (MDG 5). Seeking to advance the goals agenda, world leaders launched initiatives addressing maternal and child health. New network governance and framing strategies that closely linked maternal, newborn and child health shaped the initiatives. Diverse network composition--expanding beyond a relatively narrowly focused and technically oriented group to encompass allies and leaders that brought additional resources to bear on the problem--was crucial to maternal health's rise on the agenda in the 2000s. PMID- 26273061 TI - Comparison of long-term outcomes between children with aplastic anemia and refractory cytopenia of childhood who received immunosuppressive therapy with antithymocyte globulin and cyclosporine. AB - The 2008 World Health Organization classification proposed a new entity in childhood myelodysplastic syndrome, refractory cytopenia of childhood. However, it is unclear whether this morphological classification reflects clinical outcomes. We retrospectively reviewed bone marrow morphology in 186 children (median age 8 years; range 1-16 years) who were enrolled in the prospective study and received horse antithymocyte globulin and cyclosporine between July 1999 and November 2008. The median follow-up period was 87 months (range 1-146 months). Out of 186 patients, 62 (33%) were classified with aplastic anemia, 94 (49%) with refractory cytopenia of childhood, and 34 (18%) with refractory cytopenia with multilineage dysplasia. Aplastic anemia patients received granulocyte colony stimulating factor more frequently and for longer durations than other patients (P<0.01). After six months, response rates to immunosuppressive therapy were not significantly different among the 3 groups. Acquisition of chromosomal abnormalities was observed in 5 patients with aplastic anemia, 4 patients with refractory cytopenia of childhood, and 3 patients with refractory cytopenia with multilineage dysplasia. Although the cumulative incidence of total clonal evolution at ten years was not significantly different among the 3 groups, the cumulative incidence of monosomy 7 development was significantly higher in aplastic anemia than in the other groups (P=0.02). Multivariate analysis revealed that only granulocyte colony-stimulating factor administration duration of 40 days or more was a significant risk factor for monosomy 7 development (P=0.02). These findings suggest that even the introduction of a strict morphological distinction from hypoplastic myelodysplastic syndrome cannot eradicate clonal evolution in children with aplastic anemia. PMID- 26273063 TI - Safe and Reproducible Preparation of Functional Dendritic Cells for Immunotherapy in Glioblastoma Patients. AB - Cell therapy based on dendritic cells (DCs) pulsed with tumor lysate is a promising approach in addition to conventional therapy for the treatment of patients with glioblastoma (GB). The success of this approach strongly depends on the ability to generate high-quality, functionally mature DCs (mDCs), with a high level of standardization and in compliance with Good Manufacturing Practices. In the cell factory of the Carlo Besta Foundation, two phase I clinical trials on immunotherapy with tumor lysate-loaded DCs as treatment for GB are ongoing. From 2010 to 2014, 54 patients were enrolled in the studies and 54 batches of DCs were prepared. We retrospectively analyzed the results of the quality control tests carried out on each produced batch, evaluating yield of mDCs and their quality in terms of microbiological safety and immunological efficacy. The number of mDCs obtained allowed the treatment of all the enrolled patients. All 54 batches were sterile, conformed to acceptable endotoxin levels, and were free of Mycoplasma species and adventitious viruses. During culture, cells maintained a high percentage of viability (87%-98%), and all batches showed high viability after thawing (mean+/-SD: 94.6%+/-2.9%). Phenotype evaluation of mDCs showed an evident upregulation of markers typical of DC maturation; mixed lymphocyte reaction tests for the functional evaluation of DCs demonstrated that all batches were able to induce lymphocyte responses. These results demonstrated that our protocol for DC preparation is highly reproducible and permits generation of large numbers of safe and functional DCs for in vivo use in immunotherapy approaches. SIGNIFICANCE: Cell therapy based on antigen-pulsed dendritic cells (DCs) is a promising approach for the treatment of glioblastoma patients. The success of this approach strongly depends on the ability to generate high-quality, functional DCs with a high level of standardization, ensuring reproducibility, efficacy, and safety of the final product. This article summarizes the results of the quality controls on 54 batches, to demonstrate the feasibility of producing a therapeutic cell-based vaccine via a well-controlled Good Manufacturing Practices (GMP)-compliant production process. The findings may be of scientific interest to those working in the field of preparation of GMP-compliant products for cell therapy applications. PMID- 26273066 TI - Joint statement on redundant (duplicate) publication by the Editors of the undersigned cardio-thoracic journals. PMID- 26273065 TI - Feasibility Study of Canine Epidermal Neural Crest Stem Cell Transplantation in the Spinal Cords of Dogs. AB - This pilot feasibility study aimed to determine the outcome of canine epidermal neural crest stem cell (cEPI-NCSC) grafts in the normal spinal cords of healthy bred-for-research dogs. This included developing novel protocols for (a) the ex vivo expansion of cEPI-NCSCs, (b) the delivery of cEPI-NCSCs into the spinal cord, and (c) the labeling of the cells and subsequent tracing of the graft in the live animal by magnetic resonance imaging. A total of four million cEPI-NCSCs were injected into the spinal cord divided in two locations. Differences in locomotion at baseline and post-treatment were evaluated by gait analysis and compared with neurological outcome and behavioral exams. Histopathological analyses of the spinal cords and cEPI-NCSC grafts were performed at 3 weeks post transplantation. Neurological and gait parameters were minimally affected by the stem cell injection. cEPI-NCSCs survived in the canine spinal cord for the entire period of investigation and did not migrate or proliferate. Subsets of cEPI-NCSCs expressed the neural crest stem cell marker Sox10. There was no detectable expression of markers for glial cells or neurons. The tissue reaction to the cell graft was predominantly vascular in addition to a degree of reactive astrogliosis and microglial activation. In the present study, we demonstrated that cEPI-NCSC grafts survive in the spinal cords of healthy dogs without major adverse effects. They persist locally in the normal spinal cord, may promote angiogenesis and tissue remodeling, and elicit a tissue response that may be beneficial in patients with spinal cord injury. SIGNIFICANCE: It has been established that mouse and human epidermal neural crest stem cells are somatic multipotent stem cells with proved innovative potential in a mouse model of spinal cord injury (SCI) offering promise of a valid treatment for SCI. Traumatic SCI is a common neurological problem in dogs with marked similarities, clinically and pathologically, to the syndrome in people. For this reason, dogs provide a readily accessible, clinically realistic, spontaneous model for evaluation of epidermal neural crest stem cells therapeutic intervention. The results of this study are expected to give the baseline data for a future clinical trial in dogs with traumatic SCI. PMID- 26273067 TI - Osteopontin alters endothelial and valvular interstitial cell behaviour in calcific aortic valve stenosis through HMGB1 regulation. AB - OBJECTIVES: Calcific aortic valve stenosis (CAVS) is an important clinical problem predominantly affecting elderly individuals. Studies suggest that the progression of CAVS is actively regulated with valve endothelial injury leading to inflammation, fibrosis and calcification. The aim of this study was to delineate the possible regulatory role of osteopontin (OPN) on high-mobility group box 1 (HMGB1) function and the associated inflammatory and fibrotic response in CAVS. METHODS: Aortic valve leaflets were collected from CAVS patients undergoing aortic valve replacement (n = 40), and control aortic valve leaflets were obtained from heart transplant recipients (n = 15). Valves and plasma were analysed by quantitative real-time polymerase chain reaction (PCR), immunohistochemical staining and Western blot. Recombinant OPN or neutralizing OPN antibody was added to cultured endothelial and valvular interstitial cells (VICs), and cell proliferation scores and HMGB1 expression were assessed. RESULTS: CAVS valves had a decreased total percentage of VICs but increased numbers of infiltrating macrophages relative to control valves. RT-PCR studies showed higher expression of OPN, the inflammatory cytokine tumour necrosis factor alpha as well as markers of fibrosis, tissue inhibitor of matrix metalloproteinase 1 and matrix metalloproteinase 2 in CAVS valves. Elevated expression of OPN was also observed in plasma of CAVS patients compared with controls. HMGB1 was detected in the secretory granules of cultured valve endothelial and VICs derived from CAVS valves. The addition of exogenous OPN inhibited the proliferation of cultured endothelial and VICs from CAVS valves and was associated with the extracellular expression of HMGB1, whereas neutralizing OPN had the opposite effect. CONCLUSIONS: We conclude that altered OPN expression in CAVS affects cellular HMGB1 function inducing cytoplasmic translocation and secretion of HMGB1 in endothelial cells and VICs, thus indicating a regulatory role for OPN in the progression of CAVS through alteration of HMGB1 function. PMID- 26273064 TI - Chorion Mesenchymal Stem Cells Show Superior Differentiation, Immunosuppressive, and Angiogenic Potentials in Comparison With Haploidentical Maternal Placental Cells. AB - Mesenchymal stem cells (MSCs) of placental origin have become increasingly translational owing to their abundance and accessibility. MSCs of different origin share several features but also present biological differences that might point to distinct clinical properties. Hence, mixing fetal and maternal cells from the same placenta can lead to contradicting results. We analyzed the biological characteristics of haploidentical MSCs isolated from fetal sources, including the umbilical cord (UC-MSCs) and chorion (Ch-MSCs), compared with maternal decidua MSCs (Dc-MSCs). All MSCs were analyzed for general stem cell properties. In addition, immunosuppressive capacity was assessed by the inhibition of T-cell proliferation, and angiogenic potential was evaluated in a Matrigel transplantation assay. The comparison between haploidentical MSCs displayed several distinct features, including (a) marked differences in the expression of CD56, (b) a higher proliferative capacity for Dc-MSCs and UC-MSCs than for Ch-MSCs, (c) a diversity of mesodermal differentiation potential in favor of fetal MSCs, (d) a higher capacity for Ch-MSCs to inhibit T-cell proliferation, and (e) superior angiogenic potential of Ch-MSCs evidenced by a higher capability to form tubular vessel-like structures and an enhanced release of hepatocyte growth factor and vascular endothelial growth factor under hypoxic conditions. Our results suggest that assessing the prevalence of fetomaternal contamination within placental MSCs is necessary to increase robustness and limit side effects in their clinical use. Finally, our work presents evidence positioning fetoplacental cells and notably Ch-MSCs in the forefront of the quest for cell types that are superior for applications in regenerative medicine. SIGNIFICANCE: This study analyzed the biological characteristics of mesenchymal stem cells (MSCs) isolated from fetal and maternal placental origins. The findings can be summarized as follows: (a) important differences were found in the expression of CD56, (b) a different mesodermal differentiation potential was found in favor of fetal MSCs, (c) a higher immunosuppressive capacity for chorion MSCs was noted, and (d) superior angiogenic potential of Ch-MSCs was observed. These results suggest that assessing the prevalence of fetomaternal contamination within placental MSCs is necessary to increase robustness and limit side effects in their clinical use. The evidence should allow clinicians to view fetoplacental cells, notably Ch-MSCs, favorably as candidates for use in regenerative medicine. PMID- 26273068 TI - Transatrial left-ventricular cannulation in acute aortic dissection type A: a novel cannulation technique. AB - Despite improvements in surgical and perfusion techniques, surgery for acute aortic dissection type A (AADA) remains associated with high mortality rates. All cannulation techniques currently used to establish arterial flow are associated with a varying but considerable risk of organ malperfusion, neurological complications or additional access site trauma. We introduce Rahimi's transatrial cannulation of the left ventricle via the right upper pulmonary vein as an innovative alternative for antegrade, arterial return in AADA. PMID- 26273069 TI - Single-port video-assisted thoracoscopic mediastinal tumour resection. AB - OBJECTIVES: To present the technique of single-port video-assisted thoracoscopic mediastinal tumour resection, which includes limited thymectomy, extended thymectomy, cyst excision and posterior mediastinal tumour excision, and the early results of resection with the use of this technique. METHODS: Twenty-nine patients with mediastinal tumours were treated with single-port thoracoscopic mediastinal resection at Chung Gung Memorial Hospital between April 2014 and May 2015.The surgical intervention was performed through the fourth or fifth intercostal space at the anterior axillary line. A 5- or 10-mm 30 degrees video camera and working instruments were employed simultaneously at this incision site throughout the surgery. The perioperative variables and outcomes were collected and analysed retrospectively. RESULTS: Among the 29 cases included in the final analysis, 8 extended thymectomies, 5 limited thymectomies, 7 cyst excisions and 9 tumour excisions were performed successfully without the need for conversion. For the 29 patients who underwent single-port video-assisted thoracoscopic surgery (VATS), the mean operation time was 97.3 +/- 31.2 min and the average blood loss was 34.1 +/- 45.7 ml. The average length of the incision wound was 3.41 +/- 0.76 cm and the average length of postoperative hospital stay was 3.75 +/- 1.53 days. There were no mortalities, and mobility was achieved 30 days after surgery. CONCLUSIONS: With regard to oncological concerns, the occurrence of postoperative myasthenia gravis or freedom from tumour recurrence is a paramount issue. Our cohort follow-up time was not long enough to address this, and more time and patients are needed for further evaluation. But our preliminary report showed that uniportal VATS for mediastinal tumour resection was a promising and safe technique with regard to short-term clinical outcome. PMID- 26273070 TI - Off-pump coronary endarterectomy with stent removal for in-stent restenosis in the left anterior descending artery. AB - OBJECTIVES: In-stent restenosis (ISR) remains a major complication of percutaneous coronary intervention, even in the current era of drug-eluting stents (DESs). We reviewed the clinical and angiographic outcomes of coronary endarterectomy with stent removal using an off-pump technique in patients with ISR in the left anterior descending artery (LAD). METHODS: Twelve patients with long-segment ISR in the LAD underwent off-pump coronary artery bypass grafting with coronary endarterectomy and stent removal at our institution from November 2005 to August 2012. Their mean age was 65.0 +/- 6.3 years, and 11 were male. DESs were used in 10 patients and bare-metal stents were used in the remaining 2 patients. The interval from the latest intervention ranged from 4 to 102 months (median, 12 months). RESULTS: None of the procedures were converted to on-pump surgery, and there were no operative deaths. The left internal thoracic artery (LITA) was used to reconstruct the endarterectomized LAD in all patients, and the mean length of the arteriotomy in the LAD was 5.3 +/- 1.0 cm. The LITA and LAD were patent in all patients on both early postoperative and follow-up angiography. At the median 24-month follow-up (range, 12-78 months), there were no late deaths and all patients were at a Canadian Cardiovascular Society class of 0 or I. CONCLUSIONS: Coronary endarterectomy with stent removal can be safely performed using an off-pump technique and provides favourable clinical and angiographic outcomes in patients with long-segment ISR in the LAD. PMID- 26273071 TI - Field triage in the ambulance versus referral via non-percutaneous coronary intervention centre in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: A systematic review. AB - AIMS: The purpose of this study was to determine whether direct ambulance transport of ST-elevation myocardial infarction (STEMI) patients to a percutaneous coronary intervention (PCI) hospital (field triage) leads to a lower 30-day mortality compared to transport via a referral non-PCI hospital (referral via a spoke centre) in STEMI patients. METHODS AND RESULTS: We performed a systematic review of interventions. An experienced librarian searched in PubMed, EMBASE.com and The Cochrane Library (via Wiley) from January 1980-February 2013. Studies that examined field triage and/or referral via a spoke centre in STEMI patients treated with primary or facilitated PCI were included. Two authors independently conducted the study selection and data extraction. Multivariable frequency weighted logistic regression analysis was performed to assess the effect of the type of transfer on the outcome measures. We identified 14 randomised clinical trials (RCTs), including 20 transfer groups and 4474 participants. Thirty-day mortality was lower in patients who underwent field triage (3.0%; 95% confidence interval (CI) 2.2-4.2) compared to patients who were referred via a spoke centre (4.7%; 95% CI 4.0-5.5). In multivariable frequency weighted logistic regression analysis, field triage was independently associated with a lower incidence of 30-day mortality (odds ratio (OR): 0.58; 95% CI 0.37 0.89). CONCLUSION: Field triage compared to referral via a spoke centre leads to a lower 30-day mortality in STEMI patients. Therefore, direct ambulance transport to a PCI hospital should become the transfer type for STEMI patients. PMID- 26273072 TI - Prescribing marijuana for chronic pain. PMID- 26273074 TI - Addressing the need for standardized concussion care in Canada: Concussion Awareness Training Tool. PMID- 26273075 TI - Advance care planning: Let's start sooner. PMID- 26273076 TI - Complementing undergraduate medical training. PMID- 26273077 TI - Complete dissociation from the health care and pharmaceutical industry. PMID- 26273078 TI - Response. PMID- 26273079 TI - Correction. PMID- 26273081 TI - Low FODMAP diet. PMID- 26273080 TI - Guideline for primary care management of headache in adults. AB - OBJECTIVE: To increase the use of evidence-informed approaches to diagnosis, investigation, and treatment of headache for patients in primary care. QUALITY OF EVIDENCE: A comprehensive search was conducted for relevant guidelines and systematic reviews published between January 2000 and May 2011. The guidelines were critically appraised using the AGREE (Appraisal of Guidelines for Research and Evaluation) tool, and the 6 highest-quality guidelines were used as seed guidelines for the guideline adaptation process. MAIN MESSAGE: A multidisciplinary guideline development group of primary care providers and other specialists crafted 91 specific recommendations using a consensus process. The recommendations cover diagnosis, investigation, and management of migraine, tension-type, medication-overuse, and cluster headache. CONCLUSION: A clinical practice guideline for the Canadian health care context was created using a guideline adaptation process to assist multidisciplinary primary care practitioners in providing evidence-informed care for patients with headache. PMID- 26273082 TI - What's new in Alzheimer disease? PMID- 26273083 TI - Abnormal uterine bleeding: Taking the stress out of controlling the flow. PMID- 26273084 TI - Jennifer A. Parker MD CCFP. PMID- 26273085 TI - Friday mornings. PMID- 26273087 TI - Carter versus Canada: effects on us and our profession. PMID- 26273092 TI - Differential Genetic Effects on Statin-Induced Changes Across Low-Density Lipoprotein-Related Measures. AB - BACKGROUND: Statin therapy influences not only low-density lipoprotein (LDL) cholesterol levels but also LDL-related biomarkers, including non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B, total number of LDL particles, and mean LDL particle size. Recent studies have identified many genetic loci influencing circulating lipid levels and statin-induced LDL cholesterol reduction. However, it is unknown how these genetic variants influence statin-induced changes in LDL subfractions and non-HDL-C. METHODS AND RESULTS: One hundred sixty candidate single-nucleotide polymorphisms for effects on circulating lipid levels or statin-induced LDL-cholesterol lowering were tested for association with response of LDL subfractions and non-HDL-C to rosuvastatin or placebo for 1 year among 7046 participants from the Justification for Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial. Of the 51 single-nucleotide polymorphisms associated with statin response for >= 1 of the LDL subfractions or non-HDL-C, 20 single-nucleotide polymorphisms could be clustered according to effects predominantly on LDL particle size, predominantly on LDL particle number, and on apolipoprotein B but not on LDL cholesterol or non-HDL-C. CONCLUSIONS: These differential associations point to pathways of LDL response to statin therapy and possibly to mechanisms of statin-dependent cardiovascular disease risk reduction. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681. PMID- 26273094 TI - A Distress Protocol for Respiratory Emergencies in Terminally Ill Patients With Lung Cancer or Chronic Obstructive Pulmonary Disease. AB - A combination of opioid, midazolam, and scopolamine (that we call "distress protocol" [DP]) is used to induce transient sedation when emergencies occur in palliative care. We wished to describe the prescription and administration of DP in terminally ill patients with either lung cancer or chronic obstructive pulmonary disease (COPD). In a retrospective study, 96 of 100 patients with cancer and 85 of 100 patients with COPD had a DP prescribed. Thirty patients with cancer and 29 with COPD received at least 1 DP. All patients receiving a DP for an appropriate indication were sedated within 30 minutes. There was no difference in survival from DP administration among patients who received it and those who did not. PMID- 26273095 TI - Safe staffing in emergency departments. PMID- 26273093 TI - A Protocol for the Control of Agitation in Palliative Care. AB - BACKGROUND: Agitation is a distressing and dangerous behavior for all involved. OBJECTIVE: To study a protocol effectiveness and safety. METHODS: The time when the protocol was initiated and when the agitation was controlled, the number of doses needed and the complications observed were recorded. RESULTS: One hundred and thirty-five inpatients of a palliative care service were included. The most frequent diagnosis was head and neck cancer, 37 (27%). The protocol was used 584 times, from 1 to 31 times on each patient, median of 3 times. Five hundred and thirty-four (91%) agitation episodes were controlled with only the first dose of the protocol, without significant complications. CONCLUSION: From those results, it can be said that this protocol is effective and safe. PMID- 26273097 TI - Removing a Titanium wedding ring. PMID- 26273096 TI - Safe staffing for nursing in emergency departments: evidence review. AB - OBJECTIVE: Getting staffing levels wrong in hospitals is linked to excess mortality and poor patient experiences but establishing the safe nurse staffing levels in the emergency department (ED) is challenging because patient demand is so variable. This paper reports a review conducted for the National Institute for Health and Care Excellence (NICE) which sought to identify the research evidence to inform UK nursing workforce planning. DESIGN: We searched 10 electronic databases and relevant websites for English language studies published from 1994. Studies included reported a direct measure of nurse staffing relative to an activity measure (eg, attendances, patient throughput) or an estimate of nurse staffing requirements. Randomised or non-randomised trials, prospective or retrospective observational, cross-sectional or correlational studies, interrupted time-series, and controlled before and after studies were considered. RESULTS: We identified 16,132 items via databases and 2193 items through manual and other searching. After title/abstract screening (by one reviewer, checked by a second) 55 studies underwent full assessment by the review team. 18 studies met the inclusion criteria for the NICE review, however 3 simulation studies that reported simulated rather than measured outcomes are not reported here. CONCLUSIONS: The evidence is weak but indicates that levels of nurse staffing in the ED are associated with patients leaving without being seen, ED care time and patient satisfaction. Lower staffing is associated with worse outcomes. There remain significant gaps and in particular a lack of evidence on the impact of staffing on direct patient outcomes and adequate economic analyses to inform decisions about nurse staffing. Given that an association between nurse staffing levels and patient outcomes on inpatient wards has been demonstrated, this gap in the evidence about nurse staffing in EDs needs to be addressed. PMID- 26273098 TI - Fibroblast Growth Factor 23 Is an Independent and Specific Predictor of Mortality in Patients With Heart Failure and Reduced Ejection Fraction. AB - BACKGROUND: Strategies to improve risk prediction are of major importance in patients with heart failure (HF). Fibroblast growth factor 23 (FGF-23) is an endocrine regulator of phosphate and vitamin D homeostasis associated with an increased cardiovascular risk. We aimed to assess the prognostic effect of FGF-23 on mortality in HF patients with a particular focus on differences between patients with HF with preserved ejection fraction and patients with HF with reduced ejection fraction (HFrEF). METHODS AND RESULTS: FGF-23 levels were measured in 980 patients with HF enrolled in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study including 511 patients with HFrEF and 469 patients with HF with preserved ejection fraction and a median follow-up time of 8.6 years. FGF-23 was additionally measured in a second cohort comprising 320 patients with advanced HFrEF. FGF-23 was independently associated with mortality with an adjusted hazard ratio per 1-SD increase of 1.30 (95% confidence interval, 1.14-1.48; P<0.001) in patients with HFrEF, whereas no such association was found in patients with HF with preserved ejection fraction (for interaction, P=0.043). External validation confirmed the significant association with mortality with an adjusted hazard ratio per 1 SD of 1.23 (95% confidence interval, 1.02-1.60; P=0.027). FGF-23 demonstrated an increased discriminatory power for mortality in addition to N-terminal pro-B-type natriuretic peptide (C-statistic: 0.59 versus 0.63) and an improvement in net reclassification index (39.6%; P<0.001). CONCLUSIONS: FGF-23 is independently associated with an increased risk of mortality in patients with HFrEF but not in those with HF with preserved ejection fraction, suggesting a different pathophysiologic role for both entities. PMID- 26273100 TI - Energy and metabolic alterations in predisposition to pheochromocytomas and paragangliomas: the so-called Warburg (and more) effect, 15 years on. PMID- 26273099 TI - Hypomagnesemia and functional hypoparathyroidism due to novel mutations in the Mg channel TRPM6. AB - Primary hypomagnesemia with secondary hypocalcemia (HSH) is an autosomal recessive disorder characterized by neuromuscular symptoms in infancy due to extremely low levels of serum magnesium and moderate to severe hypocalcemia. Homozygous mutations in the magnesium transporter gene transient receptor potential cation channel member 6 (TRPM6) cause the disease. HSH can be misdiagnosed as primary hypoparathyroidism. The aim of this study was to describe the genetic, clinical and biochemical features of patients clinically diagnosed with HSH in a Norwegian cohort. Five patients in four families with clinical features of HSH were identified, including one during a national survey of hypoparathyroidism. The clinical history of the patients and their families were reviewed and gene analyses of TRPM6 performed. Four of five patients presented with generalized seizures in infancy and extremely low levels of serum magnesium accompanied by moderate hypocalcemia. Two of the patients had an older sibling who died in infancy. Four novel mutations and one large deletion in TRPM6 were identified. In one patient two linked homozygous mutations were located in exon 22 (p.F978L) and exon 23 (p.G1042V). Two families had an identical mutation in exon 25 (p.E1155X). The fourth patient had a missense mutation in exon 4 (p.H61N) combined with a large deletion in the C-terminal end of the gene. HSH is a potentially lethal condition that can be misdiagnosed as primary hypoparathyroidism. The diagnosis is easily made if serum magnesium is measured. When treated appropriately with high doses of oral magnesium supplementation, severe hypomagnesemia is uncommon and the long-term prognosis seems to be good. PMID- 26273101 TI - 15 YEARS OF PARAGANGLIOMA: Pheochromocytoma, paraganglioma and genetic syndromes: a historical perspective. AB - The last decades have elucidated the genetic basis of pheochromocytoma (PC) and paraganglioma (PGL) (PCPGL)-associated hereditary syndromes. However, the history of these syndromes dates back at least another 150 years. Detailed descriptions by clinicians and pathologists in the 19th and 20th centuries led to the recognition of the PCPGL-associated syndromes von Hippel-Lindau disease, neurofibromatosis type 1, and multiple endocrine neoplasia type 2. In the beginning of the current millennium the molecular basis of the hereditary PGL syndrome was elucidated by the discovery of mutations in genes encoding enzymes of the Krebs cycle, such as succinate dehydrogenase genes (SDHx) and other mutations, causing 'pseudo-hypoxia' signaling. These recent developments also marked a paradigm shift. It reversed the traditional order of genetic research that historically aimed to define the genetic basis of a known hereditary syndrome but now is challenged with defining the full clinical phenotype associated with a newly defined genetic basis. This challenge underscores the importance to learn from medical history, continue providing support for clinical research, and train physicians with regards to their skills to identify patients with PCPGL-associated syndromes to extend our knowledge of the associated phenotype. This historical overview provides details on the history of the paraganglial system and PCPGL-associated syndromes. As such, it hopefully will not only be an interesting reading for the physician with a historical interest but also emphasize the necessity of ongoing astute individual clinical observations and clinical registries to increase our knowledge regarding the full phenotypic spectrum of these conditions. PMID- 26273103 TI - Longevity of biventricular defibrillators: not all devices are created equal. PMID- 26273104 TI - Management of patients with ventricular tachycardia in Europe: results of the European Heart Rhythm Association survey. AB - The purpose of this European Heart Rhythm Association (EHRA) survey was to assess clinical practice in the management of ventricular tachycardia (VT). The data are based on an electronic questionnaire sent to the members of the EHRA Research Network. Responses were received from 31 centres in 16 countries. The results of the survey show that the management of VT is in general in accordance with guidelines. Antiarrhythmic drugs are still frequently used for VT treatment. In patients at high risk of sudden cardiac death, an implantable cardioverter defibrillator is routinely recommended, while the treatment options vary for patients with moderate or low risk. A discreet attitude is adopted for catheter ablation in high-risk patients as demonstrated by a relatively low rate of catheter ablation. PMID- 26273105 TI - Using Negotiated Joining to Construct and Fill Open-ended Roles in Elite Culinary Groups. AB - This qualitative study examines membership processes in groups operating in an uncertain environment that prevents them from fully predefining new members' roles. I describe how nine elite high-end, cutting-edge culinary groups in the U.S. and Europe, ranging from innovative restaurants to culinary R&D groups, use negotiated joining-a previously undocumented process-to systematically construct and fill these emergent, open-ended roles. I show that negotiated joining is a consistently patterned, iterative process that begins with a role that both aspirant and target group explicitly understand to be provisional. This provisional role is then jointly modified and constructed by the aspirant and target group through repeated iterations of proposition, validation through trial and evaluation, and selective integration of validated role components. The initially provisional role stabilizes and the aspirant achieves membership if enough role components are validated; otherwise the negotiated joining process is abandoned. Negotiated joining allows the aspirant and target group to learn if a mutually desirable role is likely and, if so, to construct such a role. In addition, the provisional roles in negotiated joining can support absorptive capacity by allowing novel role components to enter target groups through aspirants' efforts to construct stable roles for themselves, while the internal adjustment involved in integrating newly validated role components can have the unintended side effect of supporting adaptation by providing opportunities for the groups to use these novel role components to modify their role structure and goals to suit a changing and uncertain environment. Negotiated joining thus reveals role ambiguity's hitherto unexamined beneficial consequences and provides a foundation for a contingency theory of new-member acquisition. PMID- 26273106 TI - The evolution of antipredator behaviour following relaxed and reversed selection in Alaskan threespine stickleback fish. AB - Changing environments, whether through natural or anthropogenic causes, can lead to the loss of some selective pressures ('relaxed selection') and possibly even the reinstatement of selective agents not encountered for many generations ('reversed selection'). We examined the outcome of relaxed and reversed selection in the adaptive radiation of the threespine stickleback fish, Gasterostues aculeatus L., in which isolated populations encounter a variety of predation regimes. Oceanic stickleback, which represent the ancestral founders of the freshwater radiation, encounter many piscivorous fish. Derived, freshwater populations, on the other hand, vary with respect to the presence of predators. Some populations encounter native salmonids, whereas others have not experienced predation by large fish in thousands of generations (relax-selected populations). Some relax-selected populations have had sport fish, including rainbow trout, Oncorhynchus mykiss, introduced within the past several decades (reverse selected). We examined the behavioural responses of stickleback from three populations of each type to simulated attacks by trout and birds to determine whether relaxed and reversed selection has led to divergence in behaviour, and whether this divergence was predator specific. Fish from trout-free populations showed weak responses to trout, as predicted, but these responses were similar to those of oceanic (ancestral) populations. Fish from populations that co-occur with trout, whether native or introduced, showed elevated antipredator responses, indicating that in freshwater, trout predation selects for enhanced antipredator responses, which can evolve extremely rapidly. Comparison of laboratory-reared and wild-caught individuals suggests a combination of learned and genetic components to this variation. Responses to a model bird flyover were weakly linked to predation environment, indicating that the loss of predation by trout may partially influence the evolution of responses to birds. Our results reject the hypothesis that the consistent presence of predatory birds has been sufficient to maintain responses to piscivorous fish under periods of relaxed selection. PMID- 26273102 TI - 15 YEARS OF PARAGANGLIOMA: Clinical manifestations of paraganglioma syndromes types 1-5. AB - The paraganglioma (PGL) syndromes types 1-5 are autosomal dominant disorders characterized by familial predisposition to PGLs, phaeochromocytomas (PCs), renal cell cancers, gastrointestinal stromal tumours and, rarely, pituitary adenomas. Each syndrome is associated with mutation in a gene encoding a particular subunit (or assembly factor) of succinate dehydrogenase (SDHx). The clinical manifestations of these syndromes are protean: patients may present with features of catecholamine excess (including the classic triad of headache, sweating and palpitations), or with symptoms from local tumour mass, or increasingly as an incidental finding on imaging performed for some other purpose. As genetic testing for these syndromes becomes more widespread, presymptomatic diagnosis is also possible, although penetrance of disease in these syndromes is highly variable and tumour development does not clearly follow a predetermined pattern. PGL1 syndrome (SDHD) and PGL2 syndrome (SDHAF2) are notable for high frequency of multifocal tumour development and for parent-of-origin inheritance: disease is almost only ever manifest in subjects inheriting the defective allele from their father. PGL4 syndrome (SDHB) is notable for an increased risk of malignant PGL or PC. PGL3 syndrome (SDHC) and PGL5 syndrome (SDHA) are less common and appear to be associated with lower penetrance of tumour development. Although these syndromes are all associated with SDH deficiency, few genotype-phenotype relationships have yet been established, and indeed it is remarkable that such divergent phenotypes can arise from disruption of a common molecular pathway. This article reviews the clinical presentations of these syndromes, including their component tumours and underlying genetic basis. PMID- 26273107 TI - Relationships Between Commuting and Social Capital Among Men and Women in Southern Sweden. AB - The societal need for a mobile workforce increases time spent commuting and thus also the total workday. How this affects individual well-being and social life is, however, surprisingly little known. We investigated the relation between commuting time and mode, and social participation and general trust in other people as measures of social capital, using data from public health surveys conducted in 2004 and 2008 in Scania, Sweden: in all, 21,088 persons ages 18 to 65 and working at least 30 hr per week. Commuting by car was significantly associated with a higher prevalence of low social participation and low general trust compared with active commuting, and the association increased with the duration of commuting time. In contrast, public commuting was not significantly associated with decreased social capital measures except among long-duration commuters, who reported lower social participation. The overall pattern was similar for men and for women. PMID- 26273108 TI - Generating Charged Pharmaceutical Aerosols Intended to Improve Targeted Drug Delivery in Ventilated Infants. AB - The delivery of pharmaceutical aerosols to infants receiving mechanical ventilation is extremely challenging due to small diameter flow passages, low tidal volumes, and frequent exhalation of the aerosol. The use of small charged particles is proposed as a novel method to prevent deposition in ventilator components and foster deposition in the lower infant airways. The objective of this study was to compare the performance of multiple new devices for generating small charged particles that are expected to maximize respiratory drug delivery in ventilated infants. Criteria used to select a leading device included production of a charged aerosol with a mass median aerodynamic diameter (MMAD) <= approximately 1.8 MUm; low device depositional loss of the aerosol (<20%); particle charge in the range of the Rayleigh limit/100; and high drug output with low performance variability. Proposed new devices were a wick electrospray (WES) system with accelerated cross-flow air; a condensational vapor (CV) system with a charged solution and strong field gradient; and a low flow - induction charger (LF-IC) designed to operate with a modified commercial mesh nebulizer. Based on infant ventilation conditions, flow rates through the devices were in a range of 2-5 L/min and the devices were assessed in terms of depositional drug loss and emitted drug mass; droplet size distribution (DSD) using a Mini-MOUDI; and DSD and net charge with a modified ELPI. Considering the WES, primary limitations were (i) low and variable aerosol production rates and (ii) high device depositional losses. The CV device produced a high quality aerosol with a MMAD of 0.14 MUm and a drug delivery rate of 25 MUg/min. However, the device was excluded because it failed to produce a charged aerosol. In contrast, the LF-IC produced a 1.6 MUm aerosol with high net charge, low device depositional loss (<15% based on recovery), and low variability. In the ELPI size fraction bin nearest the MMAD, the LF-IC produced >100 elementary charges per particle, which was an order of magnitude increase compared to the case of zero charging voltage. In conclusion, the LF-IC was selected as a leading system that is expected to improve aerosol delivery efficiency in ventilated infants through the use of small charged particles. PMID- 26273110 TI - Total Synthesis of the Aglycone of IB-00208. AB - A total synthesis of the aglycone of IB-00208 was accomplished in 22 steps using a newly developed approach towards polycyclic 1,4-dioxygenated xanthones from benzocyclobutenones. The generality of this entry to xanthones was initially established on several model systems before it was successfully applied to the construction of the hexacyclic core of the natural product. A new and potentially general approach towards angularly-fused benzocyclobutenones using ring-closing metathesis (RCM) was also developed. PMID- 26273109 TI - Exchange of Alkyl and Tris(2-mercapto-1-t-butylimidazolyl)hydroborato Ligands Between Zinc, Cadmium and Mercury. AB - The tris(2-mercaptoimidazolyl)hydroborato ligand, [TmBut ], has been used to investigate the exchange of alkyl and sulfur donor ligands between the Group 12 metals, Zn, Cd and Hg. For example, [TmBut ]2Zn reacts with Me2Zn to yield [TmBut ]ZnMe, while [TmBut ]CdMe is obtained readily upon reaction of [TmBut ]2Cd with Me2Cd. Ligand exchange is also observed between different metal centers. For example, [TmBut ]CdMe reacts with Me2Zn to afford [TmBut ]ZnMe and Me2Cd. Likewise, [TmBut ]HgMe reacts with Me2Zn to afford [TmBut ]ZnMe and Me2Hg. However, whereas the [TmBut ] ligand transfers from mercury to zinc in the methyl system, [TmBut ]HgMe/Me2Zn, transfer of the [TmBut ] ligand from zinc to mercury is observed upon treatment of [TmBut ]2Zn with HgI2 to afford [TmBut ]HgI and [TmBut ]ZnI. These observations demonstrate that the phenomenological preference for the [TmBut ] ligand to bind one metal rather than another is strongly influenced by the nature of the co-ligands. PMID- 26273111 TI - Reductive Cyclization of Halo-Ketones to Form 3-Hydroxy-2-Oxindoles via Palladium Catalyzed Hydrogenation: A Hydrogen-Mediated Grignard Addition. AB - The reductive cyclization of N-oxoacyl ortho-bromoanilides to form 3-hydroxy-2 oxindoles under the conditions of palladium catalyzed hydrogenation is described. This work may be viewed as a prelude to intermolecular hydrogen-mediated Grignard type reductive couplings of organic halides with carbonyl compounds. PMID- 26273112 TI - Gold(I)-catalyzed enantioselective [3+2] and [3+3] cycloaddition reactions of propargyl acetals/ketals. AB - An asymmetric gold(I)-catalyzed [3+2] cycloaddition of propargyl acetals/ketals and aldehydes is reported, which proceeds via stepwise migration-fragmentation of acetals/ketals and cycloaddition of the in situ generated gold-carbenoid intermediate. Various functionalized 2, 5-dihydrofurans were obtained in good yields and high enantioselectivities. Furthermore, an example of the first gold(I) catalyzed [3+3] cycloaddition of secondary propargyl ketals and nitrones is presented. PMID- 26273113 TI - Total synthesis of dihydrolysergic acid and dihydrolysergol: development of a divergent synthetic strategy applicable to rapid assembly of D-ring analogs. AB - The total syntheses of dihydrolysergic acid and dihydrolysergol are detailed based on a Pd(0)-catalyzed intramolecular Larock indole cyclization for the preparation of the embedded tricyclic indole (ABC ring system) and a subsequent powerful inverse electron demand Diels-Alder reaction of 5-carbomethoxy-1,2,3 triazine with a ketone-derived enamine for the introduction of a functionalized pyridine, serving as the precursor for a remarkably diastereoselective reduction to the N-methylpiperidine D-ring. By design, the use of the same ketone-derived enamine and a set of related complementary heterocyclic azadiene [4 + 2] cycloaddition reactions permitted the late stage divergent preparation of a series of alternative heterocyclic derivatives not readily accessible by more conventional approaches. PMID- 26273114 TI - Construction of Tertiary Chiral Centers by Pd-catalyzed Asymmetric Allylic Alkylation of Prochiral Enolate Equivalents. AB - The palladium-catalyzed decarboxylative allylic alkylation of enol carbonates derived from lactams and ketones is described. Employing these substrates with an electronically tuned Pd catalyst system trisubstituted chiral centers are produced. These stereocenters have been previously challenging to achieve using Pd complex/chiral P-N ligand systems. PMID- 26273115 TI - Diastereoselective addition of monoorganocuprates to a chiral fumarate: reaction development and synthesis of (-)-dihydroprotolichesterinic acid. AB - Recent studies of diastereoselective conjugate additions of monoorganocuprates, Li[RCuI], to chiral gamma-alkoxycrotonates and fumarates are disclosed. This methodology was applied to the shortest total synthesis of (-) dihydroprotolichesterinic acid to date, but several attempts to prepare other succinate-derived natural products, such as pilocarpine and antrodin E, were unsuccessful. PMID- 26273116 TI - Reductions of aryl bromides in water at room temperature. AB - Micellar nanoreactors derived from commercially available 'Nok' (SPGS-550-M), in the presence of Fu's catalyst and a mild hydride source (NaBH4), are useful for facile debromination of functionalized aromatic derivatives. This mild and environemntally responsible process is utlized in water at room temperature, and the reaction mixtures can be smoothly recycled. PMID- 26273117 TI - Large, Sparse Optimal Matching with Refined Covariate Balance in an Observational Study of the Health Outcomes Produced by New Surgeons. AB - Every newly trained surgeon performs her first unsupervised operation. How do the health outcomes of her patients compare with the patients of experienced surgeons? Using data from 498 hospitals, we compare 1252 pairs comprised of a new surgeon and an experienced surgeon working at the same hospital. We introduce a new form of matching that matches patients of each new surgeon to patients of an otherwise similar experienced surgeon at the same hospital, perfectly balancing 176 surgical procedures and closely balancing a total of 2.9 million categories of patients; additionally, the individual patient pairs are as close as possible. A new goal for matching is introduced, called "refined covariate balance," in which a sequence of nested, ever more refined, nominal covariates is balanced as closely as possible, emphasizing the first or coarsest covariate in that sequence. A new algorithm for matching is proposed and the main new results prove that the algorithm finds the closest match in terms of the total within-pair covariate distances among all matches that achieve refined covariate balance. Unlike previous approaches to forcing balance on covariates, the new algorithm creates multiple paths to a match in a network, where paths that introduce imbalances are penalized and hence avoided to the extent possible. The algorithm exploits a sparse network to quickly optimize a match that is about two orders of magnitude larger than is typical in statistical matching problems, thereby permitting much more extensive use of fine and near-fine balance constraints. The match was constructed in a few minutes using a network optimization algorithm implemented in R. An R package called rcbalance implementing the method is available from CRAN. PMID- 26273118 TI - Broad Energy Range Neutron Spectroscopy using a Liquid Scintillator and a Proportional Counter: Application to a Neutron Spectrum Similar to that from an Improvised Nuclear Device. AB - A novel neutron irradiation facility at the Radiological Research Accelerator Facility (RARAF) has been developed to mimic the neutron radiation from an Improvised Nuclear Device (IND) at relevant distances (e.g. 1.5 km) from the epicenter. The neutron spectrum of this IND-like neutron irradiator was designed according to estimations of the Hiroshima neutron spectrum at 1.5 km. It is significantly different from a standard reactor fission spectrum, because the spectrum changes as the neutrons are transported through air, and it is dominated by neutron energies from 100 keV up to 9 MeV. To verify such wide energy range neutron spectrum, detailed here is the development of a combined spectroscopy system. Both a liquid scintillator detector and a gas proportional counter were used for the recoil spectra measurements, with the individual response functions estimated from a series of Monte Carlo simulations. These normalized individual response functions were formed into a single response matrix for the unfolding process. Several accelerator-based quasi-monoenergetic neutron source spectra were measured and unfolded to test this spectroscopy system. These reference neutrons were produced from two reactions: T(p,n)3He and D(d,n)3He, generating neutron energies in the range between 0.2 and 8 MeV. The unfolded quasi monoenergetic neutron spectra indicated that the detection system can provide good neutron spectroscopy results in this energy range. A broad-energy neutron spectrum from the 9Be(d,n) reaction using a 5 MeV deuteron beam, measured at 60 degrees to the incident beam was measured and unfolded with the evaluated response matrix. The unfolded broad neutron spectrum is comparable with published time-of-flight results. Finally, the pair of detectors were used to measure the neutron spectrum generated at the RARAF IND-like neutron facility and a comparison is made to the neutron spectrum of Hiroshima. PMID- 26273119 TI - Juvenile Justice, Mental Health, and the Transition to Adulthood: A Review of Service System Involvement and Unmet Needs in the U.S. AB - Although adolescents are the primary focus of juvenile justice, a significant number of young people involved with this system are considered transition age youth (i.e., 16-25 years of age). The aim of this review is to summarize the specific needs of transition age youth with mental health conditions involved with the juvenile justice system, identify the multiple service systems relevant to this group, and offer recommendations for policies and practice. A comprehensive search strategy was used to identify and synthesize the literature. Findings highlight the paucity of research specific to transition age youth. Thus, we also summarized relevant research on justice-involved adolescents, with a focus evaluating its potential relevance in the context of the unique milestones of the transition age, including finishing one's education, setting and working towards vocational goals, and transitioning from ones' family of origin to more independent living situations. Existing programs and initiatives relevant to transition age youth with mental health conditions are highlighted, and nine specific recommendations for policy and practice are offered. PMID- 26273120 TI - Employment of Low-Income African American and Latino Teens: Does Neighborhood Social Mix Matter? AB - We quantify how teen employment outcomes for low-income African Americans and Latinos relate to their neighborhood conditions during ages 14-17. Data come from surveys of Denver Housing Authority (DHA) households who have lived in public housing scattered throughout Denver County. Because DHA household allocation mimics random assignment to neighborhood, this program represents a natural experiment for overcoming geographic selection bias. Our logistic and Tobit regression analyses found overall greater odds of teen employment and more hours worked for those who lived in neighborhoods with higher percentages of pre-1940 vintage housing, property crime rates and child abuse rates, though the strength of relationships was highly contingent on gender and ethnicity. Teen employment prospects of African Americans were especially diminished by residence in more socially vulnerable, violent neighborhoods, implying selective potential gains from social mixing alternatives. PMID- 26273121 TI - Neuropsychological and interpersonal antecedents of youth depression. AB - This research examined neuropsychological and interpersonal factors that jointly confer vulnerability to youth depression. We proposed that (1) a reduced posterior right hemisphere bias during the processing of facial expressions contributes to subsequent depressive symptoms in youth, and (2) maladaptive responses to interpersonal stress account for this association. Drawing from theory and research indicating sex differences in rates of hemispheric development, we also investigated sex differences in the associations among a reduced posterior right hemisphere bias, maladaptive responses to interpersonal stress, and depressive symptoms. Hypotheses were examined in a longitudinal study of 95 4th - 8th graders (M age = 12.33, SD = 1.10). Results supported the notion that a reduced posterior right hemisphere bias confers vulnerability to depressive symptoms over time in a sex-specific fashion, and implicate maladaptive stress responses as an explanatory mechanism. PMID- 26273122 TI - The long-term effects on children and adolescents of a policy providing work supports for low-income parents. AB - New Hope, an employment-based poverty-reduction intervention for adults evaluated in a random-assignment experimental design, had positive impacts on children's achievement and social behavior two and five years after random assignment. The question addressed in this paper was the following: Did the positive effects of New Hope on younger children diminish or even reverse when children reached the challenges of adolescence (eight years after random assignment)? Small positive impacts on school progress, school motivation, positive social behavior, child well-being, and parent control endured, but impacts on school achievement and problem behavior were no longer evident. The most likely reasons for lasting impacts were that New Hope families were slightly less likely to be poor, and children had spent more time in center-based child care and structured activities. New Hope represents a model policy that could produce modest improvements in the lives of low-income adults and children. PMID- 26273123 TI - The Effect of PAI-1 4G/5G Polymorphism and Clinical Factors on Coronary Artery Occlusion in Myocardial Infarction. AB - OBJECTIVE: Data on the impact of PAI-1-675 4G/5G genotype for fibrinolysis during myocardial infarction are inconsistent. The aim of our study was to evaluate the association of clinical and genetic (PAI-1-675 4G/5G polymorphism) factors with coronary artery occlusion in patients with myocardial infarction. MATERIALS AND METHODS: PAI-1-675 4G/5G detection was achieved by using Sanger sequencing in a sample of patients hospitalized for stent implantation due to myocardial infarction. We categorized the patients into two groups: patients with coronary artery occlusion and patients without coronary artery occlusion according to angiographic evaluation. RESULTS: We identified n = 122 (32.4%) 4G/4G, n = 186 (49.5%) 4G/5G, and n = 68 (18.1%) 5G/5G PAI-1 genotype carriers. Univariate and multivariate analysis showed that only the 4G/5G genotype was associated with coronary artery occlusion (OR: 1.656 and 95% CI: 1.009-2.718, p = 0.046). CONCLUSIONS: Our results showed that carriers of PAI-1 4G/5G genotype with myocardial infarction have increased odds of coronary artery occlusion more than 1.6 times in comparison to the carriers of homozygous genotypes. PMID- 26273124 TI - Optimization of synthesis and peptization steps to obtain iron oxide nanoparticles with high energy dissipation rates. AB - Magnetic Fluid Hyperthermia (MFH) uses heat generated by magnetic nanoparticles exposed to alternating magnetic fields to cause a temperature increase in tumors to the hyperthermia range (43-47 degrees C), inducing apoptotic cancer cell death. As with all cancer nanomedicines, one of the most significant challenges with MFH is achieving high nanoparticle accumulation at the tumor site. This motivates development of synthesis strategies that maximize the rate of energy dissipation of iron oxide magnetic nanoparticles, preferable due to their intrinsic biocompatibility. This has led to development of synthesis strategies that, although attractive from the point of view of chemical elegance, may not be suitable for scale-up to quantities necessary for clinical use. On the other hand, to date the aqueous co-precipitation synthesis, which readily yields gram quantities of nanoparticles, has only been reported to yield sufficiently high specific absorption rates after laborious size selective fractionation. This work focuses on improvements to the aqueous co-precipitation of iron oxide nanoparticles to increase the specific absorption rate (SAR), by optimizing synthesis conditions and the subsequent peptization step. Heating efficiencies up to 1,048 W/gFe (36.5 kA/m, 341 kHz; ILP = 2.3 nH.m2.kg-1) were obtained, which represent one of the highest values reported for iron oxide particles synthesized by co-precipitation without size-selective fractionation. Furthermore, particles reached SAR values of up to 719 W/gFe (36.5 kA/m, 341 kHz; ILP = 1.6 nH.m2.kg-1) when in a solid matrix, demonstrating they were capable of significant rates of energy dissipation even when restricted from physical rotation. Reduction in energy dissipation rate due to immobilization has been identified as an obstacle to clinical translation of MFH. Hence, particles obtained with the conditions reported here have great potential for application in nanoscale thermal cancer therapy. PMID- 26273125 TI - Does Minority Status Increase the Effect of Disability Status on Elementary Schoolchildren's Academic Achievement? AB - We investigated whether children's reading and mathematics growth trajectories from kindergarten to fifth grade inter-related, and to what extent disability and minority status interacted to predict their achievement trajectories. We conducted secondary data analysis based on a nationally representative sample of 6,446 U.S. schoolchildren from the Early Childhood Longitudinal Study Kindergarten Cohort. Results indicated that children's reading and mathematics achievement highly correlated in both initial status and growth. Being disabled or a racial/ethnic minority independently predicted lower academic achievement. However, and contrary to what might be expected from prior research on minority children's special education experiences, disability status was associated with similar academic disadvantages for minority students and White students from kindergarten to fifth grade. Growth mixture models identified a group of children with lower and lagging achievement in both reading and mathematics from kindergarten until fifth grade. PMID- 26273126 TI - Standardized Screening for Mental Health Needs of Detained Youths from Various Ethnic Origins: The Dutch Massachusetts Youth Screening Instrument-Second Version (MAYSI-2). AB - In the U.S., the Massachusetts Youth Screening Instrument-Second Version (MAYSI 2) has been shown to be a reliable and valid tool to identify youth with mental health needs upon entry in detention facilities. The present study examined the factor structure, internal consistency, and convergent validity of the Dutch MAYSI-2 administered as part of routine clinical assessments in up to 955 detained male adolescents. Standardized mental health screening questionnaires (Youth Self-Report and Strengths and Difficulties Questionnaire) were used to test the convergent validity of the Dutch MAYSI-2. Confirmatory factor analyses showed that the factor structure of the original MAYSI-2 could be replicated with the Dutch MAYSI-2. Internal consistency indices showed that the Dutch MAYSI-2 provides a reliable screening of mental health needs. In addition, the Dutch MAYSI-2 scales were related with conceptually parallel measures of the same targeted mental health needs in the total group. With a few exceptions, the internal consistency and convergent validity was supported across ethnic groups as well. Overall, these results suggest the psychometric properties of the Dutch MAYSI-2 to be promising. Implications and limitations of the current study's findings and directions for future research are discussed. PMID- 26273127 TI - Estimating added sugars in US consumer packaged goods: An application to beverages in 2007-08. AB - This study developed a method to estimate added sugar content in consumer packaged goods (CPG) that can keep pace with the dynamic food system. A team including registered dietitians, a food scientist and programmers developed a batch-mode ingredient matching and linear programming (LP) approach to estimate the amount of each ingredient needed in a given product to produce a nutrient profile similar to that reported on its nutrition facts label (NFL). Added sugar content was estimated for 7021 products available in 2007-08 that contain sugar from ten beverage categories. Of these, flavored waters had the lowest added sugar amounts (4.3g/100g), while sweetened dairy and dairy alternative beverages had the smallest percentage of added sugars (65.6% of Total Sugars; 33.8% of Calories). Estimation validity was determined by comparing LP estimated values to NFL values, as well as in a small validation study. LP estimates appeared reasonable compared to NFL values for calories, carbohydrates and total sugars, and performed well in the validation test; however, further work is needed to obtain more definitive conclusions on the accuracy of added sugar estimates in CPGs. As nutrition labeling regulations evolve, this approach can be adapted to test for potential product-specific, category-level, and population-level implications. PMID- 26273128 TI - Examining the Underlying Dimensions of Morphological Awareness and Vocabulary Knowledge. AB - We report results from two studies on the underlying dimensions of morphological awareness and vocabulary knowledge in elementary-aged children. In Study 1, 99 fourth-grade students were given multiple measures of morphological awareness and vocabulary. A single factor accounted for individual differences in all morphology and vocabulary assessments. Study 2 extended these results by giving 90 eighth-grade students expanded measures of vocabulary and morphology that assessed (a) definitional knowledge, (b) usage, (c) relational knowledge, and (d) knowledge of morphological variants, with each potential aspect of knowledge assessed using an identical set of 23 words to control for differential knowledge of specific vocabulary items. Results indicated that a single-factor model that encompassed morphological and vocabulary knowledge provided the best fit to the data. Finally, explanatory item response modeling was used to investigate sources of variance in the vocabulary and morphological awareness tasks we administered. Implications for assessment and instruction are discussed. PMID- 26273129 TI - Detecting De-gelation through Tissue Using Magnetically Modulated Optical Nanoprobes (MagMOONs). AB - Alginate gels are widely used for drug delivery and implanted devices. The rate at which these gels break down is important for controlling drug release. Since the de-gelation may be different in vivo, monitoring this process in situ is essential. However, it is challenging to monitor the gel through tissue due to optical scattering and tissue autofluorescence. Herein we describe a method to detect through tissue the chemically-induced changes in viscosity and de-gelation process of alginate gels using magnetically modulated optical nanoprobes (MagMOONs). The MagMOONs are fluorescent magnetic microspheres coated with a thin layer of opaque metal on one hemisphere. The metal layer prevents excitation and emission light from passing through one side of the MagMOONs, which creates orientation-dependent fluorescence intensity. The magnetic particles also align in an external magnetic field and give blinking signals when they rotate to follow an external modulated magnetic field. The blinking signals from these MagMOONs are distinguished from background autofluorescence and can be tracked on a single particle level in the absence of tissue, or for an ensemble average of particles blinking through tissue. When these MagMOONs are dispersed in calcium alginate gel, they become sensors for detecting gel degradation upon addition of either ammonium ion or alginate lyase. Our results show MagMOONs start blinking approximately 10 minutes after 2 mg/mL alginate lyase addition and this blinking is clearly detected even through up to 4 mm chicken breast. This approach can potentially be employed to detect bacterial biofilm formation on medical implants by sensing specific proteases that either activate a related function or regulate biofilm formation. It can also be applied to other biosensors and drug delivery systems based on enzyme-catalyzed breakdown of gel components. PMID- 26273130 TI - The domestication of Foucault: Government, critique, war. AB - Though Foucault was intrigued by the possibilities of radical social transformation, he resolutely resisted the idea that such transformation could escape the effects of power and expressed caution when it came to the question of revolution. In this article we argue that in one particularly influential line of development of Foucault's work his exemplary caution has been exaggerated in a way that weakens the political aspirations of post-Foucaldian scholarship. The site of this reduction is a complex debate over the role of normativity in Foucaldian research, where it has been claimed that Foucault's genealogical approach is unable to answer the question 'Why fight?' The terms of this debate (on the neo-Foucaldian side) are limited by a dominant though selective interpretation of Foucault's analytics of power, where power is understood primarily in terms of government, rather than struggle. In response we suggest that if we reconfigure power-as-government to power-as-war, this adjusts the central concern. 'Why fight?' becomes replaced by the more immediate question, 'How fight?' Without denying the obvious benefits of cautious scholarly work, we argue that a reconfiguration of Foucault's analytics of power might help Foucaldian research to transcend the self-imposed ethic of political quietism that currently dominates the field. PMID- 26273132 TI - Dietary selenium regulation of glutathione peroxidase mRNA and other selenium dependent parameters in male rats. AB - Weanling male rats were fed a basal torula yeast diet (0.007 MUg Se/g diet) supplemented with graded levels of Se (0 to 0.2 MUg Se/g diet as Na2SeO3) (three rats/group) to evaluate classical glutathione peroxidase (GPX1, GSH:H2O2, oxidoreductase, EC 1.11.1.9) mRNA level as an indicator of intracellular Se status. Growth was followed throughout the dietary treatment and a number of Se dependent parameters including liver GPX1 mRNA levels were determined after 33 days. Growth was not impaired at any level of dietary Se supplementation. In rats fed the Se-deficient basal diet, liver Se concentration was 5 +/- 1%, liver GPXI mRNA levels were 10 +/- 2%. plasma GPX activity was 2 +/- 1%, erythrocyte GPX activity was 37 +/- 1%, and liver GPX activity was 0 +/- 2% of the levels in rats fed 0.1 MUg Se/g diet; these parameters increased sigmoidally with increasing dietary Se, showing a breakpoint near 0.1 MUg Se/g diet. Graphical analysis indicated that the increase in liver GPX1 mRNA level with increasing dietary Se, preceded the increase in liver GPX activity. Se supplementation had no effect on polyadenylated mRNA levels or on beta-actin mRNA levels, demonstrating that Se regulation of GPX1 mRNA is specific. Se-deficient liver selenoprotein P mRNA levels were 69 +/- 2% of the levels in rats fed 0.1 MUg Se/g diet. We hypothesize that GPX1 mRNA is a primary target of the Se regulatory mechanism, making GPX1 mRNA level a potentially useful indicator of the status of an important intracellular regulatory pool of Se. PMID- 26273131 TI - Attitudes toward Physician-Nurse Collaboration in Pediatric Workers and Undergraduate Medical/Nursing Students. AB - The purpose of this study was to compare the attitudes of pediatric workers and undergraduate medical/nursing students toward collaboration. Attitude toward collaboration was measured using an adaptation of the Jefferson Scale of Attitude toward Physician-Nurse Collaboration. The 656 questionnaires were gathered from pediatrician, pediatric interns, and medical students (PIS) and pediatric nurses, nursing interns, and nursing students (NIS). Results showed a statistically significant difference in the total mean scores in attitudes towards collaboration with NIS scoring higher. Among the participants of PIS, the pediatricians obtained the highest mean scores, while, among the participants of NIS, the pediatric nurses got higher mean scores than nursing interns. It is desirable that medical and nurse schools should include interprofessional education in their curriculum to increase the understanding of the complementary roles of physicians and nurses and to encourage establishment of an interdependent relationship between them. PMID- 26273133 TI - Histone Deacetylase Inhibitor Trichostatin A Ameliorated Endotoxin-Induced Neuroinflammation and Cognitive Dysfunction. AB - Excessive production of cytokines by microglia may cause cognitive dysfunction and long-lasting behavioral changes. Activating the peripheral innate immune system stimulates cytokine secretion in the central nervous system, which modulates cognitive function. Histone deacetylases (HDACs) modulate cytokine synthesis and release. Trichostatin A (TSA), an HDAC inhibitor, is documented to be anti-inflammatory and neuroprotective. We investigated whether TSA reduces lipopolysaccharide- (LPS-) induced neuroinflammation and cognitive dysfunction. ICR mice were first intraperitoneally (i.p.) injected with vehicle or TSA (0.3 mg/kg). One hour later, they were injected (i.p.) with saline or Escherichia coli LPS (1 mg/kg). We analyzed the food and water intake, body weight loss, and sucrose preference of the injected mice and then determined the microglia activation and inflammatory cytokine expression in the brains of LPS-treated mice and LPS-treated BV-2 microglial cells. In the TSA-pretreated mice, microglial activation was lower, anhedonia did not occur, and LPS-induced cognitive dysfunction (anorexia, weight loss, and social withdrawal) was attenuated. Moreover, mRNA expression of HDAC2, HDAC5, indoleamine 2,3-dioxygenase (IDO), TNF alpha, MCP-1, and IL-1beta in the brain of LPS-challenged mice and in the LPS treated BV-2 microglial cells was lower. TSA diminished LPS-induced inflammatory responses in the mouse brain and modulated the cytokine-associated changes in cognitive function, which might be specifically related to reducing HDAC2 and HDAC5 expression. PMID- 26273134 TI - Intravenous Infusion of Dexmedetomidine Combined Isoflurane Inhalation Reduces Oxidative Stress and Potentiates Hypoxia Pulmonary Vasoconstriction during One Lung Ventilation in Patients. AB - Inhalation anesthetic isoflurane inhibits hypoxia pulmonary vasoconstriction (HPV), while dexmedetomidine (Dex) could reduce the dose of isoflurane inhalation and potentiate HPV, but the mechanism is unclear. Inhibition of reactive oxygen species (ROS) production can favor HPV during one-lung ventilation (OLV). Similarly, nitric oxide (NO), an important endothelium-derived vasodilator in lung circulation, can decrease the regional pulmonary vascular resistance of ventilated lung and reduce intrapulmonary shunting. We hypothesized that Dex may augment HPV and improve oxygenation during OLV through inhibiting oxidative stress and increasing NO release. Patients undergoing OLV during elective thoracic surgery were randomly allocated to either isoflurane + saline (NISO, n = 24) or isoflurane + dexmedetomidine (DISO, n = 25) group. Anesthesia was maintained with intravenous remifentanil and inhalational isoflurane (1.0-2.0%), with concomitant infusion of dexmedetomidine 0.7 MUgkg(-1)h(-1) in DISO and saline 0.25 mL kg(-1)h(-1) in NISO group. Hemodynamic variables or depth of anesthesia did not significantly differ between groups. Administration of Dex significantly reduced Qs/Qt and increased PaO2 after OLV, accompanied with reduced lipid peroxidation product malondialdehyde and higher levels of SOD activity as well as serum NO (all P < 0.05 DISO versus NISO). In conclusion, reducing oxidative stress and increasing NO release during OLV may represent a mechanism whereby Dex potentiates HPV. PMID- 26273135 TI - Matrix Metalloproteinase-9 Production following Cardiopulmonary Bypass Was Not Associated with Pulmonary Dysfunction after Cardiac Surgery. AB - BACKGROUND: Cardiopulmonary bypass (CPB) causes release of matrix metalloproteinase- (MMP-) 9, contributing to pulmonary infiltration and dysfunction. The aims were to investigate MMP-9 production and associated perioperative variables and oxygenation following CPB. METHODS: Thirty patients undergoing elective cardiac surgery were included. Arterial blood was sampled at 6 sequential points (before anesthesia induction, before CPB and at 2, 4, 6, and 24 h after beginning CPB) for plasma MMP-9 concentrations by ELISA. The perioperative laboratory data and variables, including bypass time, PaO2/FiO2, and extubation time, were also recorded. RESULTS: The plasma MMP-9 concentrations significantly elevated at 2-6 h after beginning CPB (P < 0.001) and returned to the preanesthesia level at 24 h (P = 0.23), with predominant neutrophil counts after surgery (P < 0.001). The plasma MMP-9 levels at 4 and 6 h were not correlated with prolonged CPB time and displayed no association with postoperative PaO2/FiO2, regardless of reduced ratio from preoperative 342.9 +/- 81.2 to postoperative 207.3 +/- 121.3 mmHg (P < 0.001). CONCLUSION: Elective cardiac surgery with CPB induced short-term elevation of plasma MMP-9 concentrations within 24 hours, however, without significant correlation with CPB time and postoperative pulmonary dysfunction, despite predominantly increased neutrophils and reduced oxygenation. PMID- 26273136 TI - Protective Effect of CXCR3+CD4+CD25+Foxp3+ Regulatory T Cells in Renal Ischemia Reperfusion Injury. AB - Regulatory T cells (Tregs) suppress excessive immune responses and are potential therapeutic targets in autoimmune disease and organ transplantation rejection. However, their role in renal ischemia-reperfusion injury (IRI) is unclear. Levels of Tregs and expression of CXCR3 in Tregs were analyzed to investigate their function in the early phase of renal IRI. Mice were randomly divided into Sham, IRI, and anti-CD25 (PC61) + IRI groups. The PC61 + IRI group was established by i.p. injection of PC61 monoclonal antibody (mAb) to deplete Tregs before renal ischemia. CD4(+)CD25(+)Foxp3(+) Tregs and CXCR3 on Tregs were analyzed by flow cytometry. Blood urea nitrogen (BUN), serum creatinine (Scr) levels, and tubular necrosis scores, all measures of kidney injury, were greater in the IRI group than in the Sham group. Numbers of Tregs were increased at 72 h after reperfusion in kidney. PC61 mAb preconditioning decreased the numbers of Tregs and aggravated kidney injury. There was no expression of CXCR3 on Tregs in normal kidney, while it expanded at 72 h after reperfusion and inversely correlated with BUN, Scr, and kidney histology score. This indicated that recruitment of Tregs into the kidney was related to the recovery of renal function after IRI and CXCR3 might be involved in the migration of Tregs. PMID- 26273137 TI - The Immediate Intramedullary Nailing Surgery Increased the Mitochondrial DNA Release That Aggravated Systemic Inflammatory Response and Lung Injury Induced by Elderly Hip Fracture. AB - Conventional concept suggests that immediate surgery is the optimal choice for elderly hip fracture patients; however, few studies focus on the adverse effect of immediate surgery. This study aims to examine the adverse effect of immediate surgery, as well as to explore the meaning of mtDNA release after trauma. In the experiment, elderly rats, respectively, received hip fracture operations or hip fracture plus intramedullary nail surgery. After fracture operations, the serum mtDNA levels as well as the related indicators of systemic inflammatory response and lung injury significantly increased in the rats. After immediate surgery, the above variables were further increased. The serum mtDNA levels were significantly related with the serum cytokine (TNF-alpha and IL-10) levels and pulmonary histological score. In order to identify the meaning of mtDNA release following hip fracture, the elderly rats received injections with mtDNA. After treatment, the related indicators of systemic inflammatory response and lung injury significantly increased in the rats. These results demonstrated that the immediate surgery increased the mtDNA release that could aggravate systemic inflammatory response and lung injury induced by elderly hip fracture; serum mtDNA might serve as a potential biomarker of systemic inflammatory response and lung injury following elderly hip fracture. PMID- 26273139 TI - Origin of Circulating Free DNA in Sepsis: Analysis of the CLP Mouse Model. AB - Recently, it has been reported that circulating free DNA (cf-DNA) in the blood is increased in various infectious diseases, including sepsis. Moreover, a relationship between cf-DNA and neutrophil extracellular traps (NETs) has been suggested. However, it is still unclear what the source and physiological role of cf-DNA in sepsis are. In this study, we examined the source of cf-DNA by detecting citrullinated histone H3, a characteristic feature of NET formation, in cecal ligation and puncture- (CLP-)operated mice. In addition, neutrophil depletion using anti-Ly6G antibodies was performed to assess the association between neutrophils and cf-DNA. Increased cf-DNA levels were observed only in CLP mice and not in the control groups; the qPCR findings revealed that the cf-DNA was mainly host-derived, even in bacteremic conditions. Citrullinated histone H3 was not increased in the neutrophils upon CLP, and the depletion of neutrophils showed limited effects on decreasing the amount of cf-DNA. Taken together, these results suggested that elevated cf-DNA levels during early-phase sepsis may represent a candidate biomarker for the severity of sepsis and that, contrary to previous findings, cf-DNA is not derived from neutrophils or NETs. PMID- 26273138 TI - Flurbiprofen Axetil Enhances Analgesic Effects of Sufentanil and Attenuates Postoperative Emergence Agitation and Systemic Proinflammation in Patients Undergoing Tangential Excision Surgery. AB - OBJECTIVE: Our present study tested whether flurbiprofen axetil could reduce perioperative sufentanil consumption and provide postoperative analgesia with decrease in emergency agitation and systemic proinflammatory cytokines release. METHODS: Ninety patients undergoing tangential excision surgery were randomly assigned to three groups: (1) preoperative dose of 100 mg flurbiprofen axetil and a postoperative dose of 2 MUg/kg sufentanil and 10 mL placebo by patient controlled analgesia (PCA) pump, (2) preoperative dose of 100 mg flurbiprofen axetil and a postoperative dose of 2 MUg/kg sufentanil and 100 mg flurbiprofen axetil by PCA pump, and (3) 10 mL placebo and a postoperative dose of 2 MUg/kg sufentanil and 10 mL placebo by PCA pump. RESULTS: Preoperative administration of flurbiprofen axetil decreased postoperative tramadol consumption and the visual analog scale at 4, 6, 12, and 24 h after surgery, which were further decreased by postoperative administration of flurbiprofen axetil. Furthermore, flurbiprofen axetil attenuated emergency agitation score and Ramsay score at 0, 5, and 10 min after extubation and reduced the TNF-alpha and interleukin- (IL-) 6 levels at 24 and 48 h after the operation. CONCLUSION: Flurbiprofen axetil enhances analgesic effects of sufentanil and attenuates emergence agitation and systemic proinflammation in patients undergoing tangential excision surgery. PMID- 26273140 TI - Hypoxic Preconditioning Suppresses Glial Activation and Neuroinflammation in Neonatal Brain Insults. AB - Perinatal insults and subsequent neuroinflammation are the major mechanisms of neonatal brain injury, but there have been only scarce reports on the associations between hypoxic preconditioning and glial activation. Here we use neonatal hypoxia-ischemia brain injury model in 7-day-old rats and in vitro hypoxia model with primary mixed glial culture and the BV-2 microglial cell line to assess the effects of hypoxia and hypoxic preconditioning on glial activation. Hypoxia-ischemia brain insult induced significant brain weight reduction, profound cell loss, and reactive gliosis in the damaged hemisphere. Hypoxic preconditioning significantly attenuated glial activation and resulted in robust neuroprotection. As early as 2 h after the hypoxia-ischemia insult, proinflammatory gene upregulation was suppressed in the hypoxic preconditioning group. In vitro experiments showed that exposure to 0.5% oxygen for 4 h induced a glial inflammatory response. Exposure to brief hypoxia (0.5 h) 24 h before the hypoxic insult significantly ameliorated this response. In conclusion, hypoxic preconditioning confers strong neuroprotection, possibly through suppression of glial activation and subsequent inflammatory responses after hypoxia-ischemia insults in neonatal rats. This might therefore be a promising therapeutic approach for rescuing neonatal brain injury. PMID- 26273141 TI - Anti-Inflammatory and Organ-Protective Effects of Resveratrol in Trauma Hemorrhagic Injury. AB - Resveratrol, a natural polyphenolic compound of grape and red wine, owns potential anti-inflammatory effects, which results in the reduction of cytokines overproduction, the inhibition of neutrophil activity, and the alteration of adhesion molecules expression. Resveratrol also possesses antioxidant, anti coagulation and anti-aging properties, and it may control of cell cycle and apoptosis. Resveratrol has been shown to reduce organ damage following traumatic and shock-like states. Such protective phenomenon is reported to be implicated in a variety of intracellular signaling pathways including the activation of estrogen receptor, the regulation of the sirtuin 1/nuclear factor-kappa B and mitogen-activated protein kinases/hemeoxygenase-1 pathway, and the mediation of proinflammatory cytokines and reactive oxygen species formation and reaction. In the recent studies, resveratrol attenuates hepatocyte injury and improves cardiac contractility due to reduction of proinflammatory mediator expression and ameliorates hypoxia-induced liver and kidney mitochondrial dysfunction following trauma and hemorrhagic injuries. Moreover, through anti-inflammatory effects and antioxidant properties, the resveratrol is believed to protect organ function in trauma-hemorrhagic injury. In this review, the organ-protective and anti inflammatory effects of resveratrol in trauma-hemorrhagic injury will be discussed. PMID- 26273142 TI - In Vivo Evaluation of the Ameliorating Effects of Small-Volume Resuscitation with Four Different Fluids on Endotoxemia-Induced Kidney Injury. AB - Acute kidney injury associated with renal hypoperfusion is a frequent and severe complication during sepsis. Fluid resuscitation is the main therapy. However, heart failure is usually lethal for those patients receiving large volumes of fluids. We compared the effects of small-volume resuscitation using four different treatment regimens, involving saline, hypertonic saline (HTS), hydroxyethyl starch (HES), or hypertonic saline hydroxyethyl starch (HSH), on the kidneys of rats treated with lipopolysaccharide (LPS) to induce endotoxemia. LPS injection caused reduced and progressively deteriorated systemic (arterial blood pressure) and renal hemodynamics (renal blood flow and renal vascular resistance index) over time. This deterioration was accompanied by marked renal functional and pathological injury, as well as an oxidative and inflammatory response, manifesting as increased levels of tumor necrosis factor-alpha, nitric oxide, and malondialdehyde and decreased activity of superoxide dismutase. Small-volume perfusion with saline failed to improve renal and systemic circulation. However, small-volume perfusion with HES and HSH greatly improved the above parameters, while HTS only transiently improved systemic and renal hemodynamics with obvious renal injury. Therefore, single small-volume resuscitation with HES and HSH could be valid therapeutic approaches to ameliorate kidney injury induced by endotoxemia, while HTS transiently delays injury and saline shows no protective effects. PMID- 26273143 TI - Captopril Pretreatment Produces an Additive Cardioprotection to Isoflurane Preconditioning in Attenuating Myocardial Ischemia Reperfusion Injury in Rabbits and in Humans. AB - BACKGROUND: Pretreatment with the angiotensin-converting inhibitor captopril or volatile anesthetic isoflurane has, respectively, been shown to attenuate myocardial ischemia reperfusion (MI/R) injury in rodents and in patients. It is unknown whether or not captopril pretreatment and isoflurane preconditioning (Iso) may additively or synergistically attenuate MI/R injury. METHODS AND RESULTS: Patients selected for heart valve replacement surgery were randomly assigned to five groups: untreated control (Control), captopril pretreatment for 3 days (Cap3d), or single dose captopril (Cap1hr, 1 hour) before surgery with or without Iso (Cap3d+Iso and Cap1hr+Iso). Rabbit MI/R model was induced by occluding coronary artery for 30 min followed by 2-hour reperfusion. Rabbits were randomized to receive sham operation (Sham), MI/R (I/R), captopril (Cap, 24 hours before MI/R), Iso, or the combination of captopril and Iso (Iso+Cap). In patients, Cap3d+Iso but not Cap1hr+Iso additively reduced postischemic myocardial injury and attenuated postischemic myocardial inflammation. In rabbits, Cap or Iso significantly reduced postischemic myocardial infarction. Iso+Cap additively reduced cellular injury that was associated with improved postischemic myocardial functional recovery and reduced myocardial apoptosis and attenuated oxidative stress. CONCLUSION: A joint use of 3-day captopril treatment and isoflurane preconditioning additively attenuated MI/R by reducing oxidative stress and inflammation. PMID- 26273144 TI - Bone Components Downregulate Expression of Toll-Like Receptor 4 on the Surface of Human Monocytic U937 Cells: A Cell Model for Postfracture Immune Dysfunction. AB - To mimic the immune status of monocyte in the localized fracture region, toll like receptor 4 (TLR4) surface expression in human monocytic U937 cells was used as the main target to assess immune dysfunction following bone component exposure. We first identified the effects of bone components (including the marrow content) on TLR4 surface expression and then examined the mechanisms underlying the changes. The level of microRNA-146a expression, an indicator of endotoxin tolerance, was also assayed. Bone component exposure downregulated TLR4 surface expression at 24 h by flow cytometry analysis, compatible with the result obtained from the membranous portion of TLR4 by western blot analysis. The cytoplasmic portion of TLR4 paradoxically increased after bone component exposure. Impaired TLR4 trafficking from the cytoplasm to the membrane was related to gp96 downregulation, as observed by western blot analysis, and this was further evidenced by gp96-TLR4 colocalization under confocal microscopy. TaqMan analysis revealed that the expression of microRNA-146a was also upregulated. This cell model demonstrated that bone component exposure downregulated TLR4 surface expression in a gp96-related manner in human monocytic U937 cells, an indicator of immunosuppression at 24 h. Immune dysfunction was further evidenced by upregulation of microRNA-146a expression at the same time point. PMID- 26273147 TI - The Health and Social Care Act 2012: The emergence of equal treatment for mental health care or another false dawn? AB - Although the National Health Service (NHS) is regarded as a national treasure, it is no longer immune from the colossal financial pressures brought about by global recession. Economic sustainability has largely driven the reform process leading to the Health and Social Care Act (HSCA) 2012, however; other considerations have also played a role in the journey to turn the health and social care service into an institution which is fit for the 21st-century needs. This article examines the impact of the HSCA 2012 on those made vulnerable through mental ill health. It then considers three issues: First, whether parity between mental and physical health can have life beyond political rhetoric; second, what impact driving up efficiency within the NHS will have upon mental health patients; and finally, the extent to which the personalisation agenda can be meaningfully applied within the mental health context. PMID- 26273145 TI - Dexmedetomidine Ameliorate CLP-Induced Rat Intestinal Injury via Inhibition of Inflammation. AB - The aim was to verify that dexmedetomidine (DEX) can attenuate CLP-induced intestinal injury via inhibition of inflammation. Male Sprague-Dawley (SD) rats were randomly allocated into Sham group and the other three CLP model groups, in terms of different treatments: placebo, DEX, and yohimbine plus DEX (DEX + YOH) groups. Pathology examination was conducted with HE stain. To identify differences among groups, the levels of DAO, and D-lactate in serum were measured by spectrophotometry, and the levels of TNF-alpha, IL-1beta, and IL-6 in serum and organ were measured by ELISA. The expressions of occludin and TLR4 in tissue were detected by Western blot. The survival rate of an additional group of animals within 7 d was recorded. In DEX group, mortality was lower, histology change was minor, DAO, and D-lactate levels were reduced, and occludin expression was increased; the expressions of TNF-alpha, IL-1beta, IL-6, and TLR4 were also decreased in DEX group. These results indicated that acute intestinal injury induced by CLP was mitigated by DEX treatment. However, these effects of DEX were significantly attenuated by yohimbine in DEX + YOH group. Our study indicated the protective effects of DEX on CLP-induced injury, which may be associated with the inhibition of inflammation via modulating TLR4 pathway and can be blocked by yohimbine. PMID- 26273146 TI - I-gel Laryngeal Mask Airway Combined with Tracheal Intubation Attenuate Systemic Stress Response in Patients Undergoing Posterior Fossa Surgery. AB - BACKGROUND: The adverse events induced by intubation and extubation may cause intracranial hemorrhage and increase of intracranial pressure, especially in posterior fossa surgery patients. In this study, we proposed that I-gel combined with tracheal intubation could reduce the stress response of posterior fossa surgery patients. METHODS: Sixty-six posterior fossa surgery patients were randomly allocated to receive either tracheal tube intubation (Group TT) or I-gel facilitated endotracheal tube intubation (Group TI). Hemodynamic and respiratory variables, stress and inflammatory response, oxidative stress, anesthesia recovery parameters, and adverse events during emergence were compared. RESULTS: Mean arterial pressure and heart rate were lower in Group TI during intubation and extubation (P < 0.05 versus Group TT). Respiratory variables including peak airway pressure and end-tidal carbon dioxide tension were similar intraoperative, while plasma beta-endorphin, cortisol, interleukin-6, tumor necrosis factor alpha, malondialdehyde concentrations, and blood glucose were significantly lower in Group TI during emergence relative to Group TT. Postoperative bucking and serious hypertensions were seen in Group TT but not in Group TI. CONCLUSION: Utilization of I-gel combined with endotracheal tube in posterior fossa surgery patients is safe which can yield more stable hemodynamic profile during intubation and emergence and lower inflammatory and oxidative response, leading to uneventful recovery. PMID- 26273148 TI - Personalized Immunomodulatory Therapy for Atopic Dermatitis: An Allergist's View. AB - The current standard medical therapy for atopic dermatitis (AD) mainly focuses on symptomatic relief by controlling skin inflammation with topical corticosteroids and/or topical calcineurin inhibitors. However, the clinical efficacy of pharmacological therapy is often disappointing to both patients and physicians. The terminology of AD contains a historical meaning of eczematous dermatitis caused by hypersensitivity reaction to environmental inhalant or food allergen. Complex interrelationships among genetic abnormalities, environmental triggers, skin barrier defects, and immune dysfunction resulting in a vicious domino-circle seem to be involved in the development and maintenance of AD. In the viewpoint of AD as an allergic disease, complete avoidance of clinically relevant allergen or induction of specific immune tolerance through administrations of allergen (allergen immunotherapy) can provide clinical remission by breaking the vicious domino-circle maintaining a chronic disease state. In recent clinical studies, monoclonal antibodies including the anti-interleukin-4 receptor antibody and anti B cell antibody induced significant clinical improvements in patients with AD. The detailed characteristics of immune dysfunction are heterogeneous among patients with AD. Therefore, a personalized combination of immunomodulatory therapies to reduce hypersensitivity (allergen immunotherapy) and correct immune dysfunction (monoclonal antibody therapy) could be a reasonable therapeutic approach for patients with AD. Future immunomodulatory therapies for AD should be developed to achieve long-term treatment-free clinical remission by induction of immune tolerance. PMID- 26273149 TI - Protease-Activated Receptor-2 Is Associated with Terminal Differentiation of Epidermis and Eccrine Sweat Glands. AB - BACKGROUND: Protease-activated receptor 2 (PAR-2) participates in various biological activities, including the regulation of epidermal barrier homeostasis, inflammation, pain perception, and melanosome transfer in the skin. OBJECTIVE: To evaluate the basic physiological role of PAR-2 in skin. METHODS: We investigated PAR-2 expression in human epidermis, skin tumors, and cultured epidermal cells using western blot and immunohistochemical analysis. Additionally, we examined the effect of the PAR-2 agonist, SLIGRL-NH2, on cultured keratinocytes. RESULTS: Strong PAR-2 immunoreactivity was observed in the granular layer of normal human skin and the acrosyringium of the eccrine sweat glands. In contrast, weak PAR-2 immunoreactivity was seen in the granular layer of callused skin and in the duct and gland cells of the eccrine sweat glands. Interestingly, PAR-2 immunoreactivity was very weak or absent in the tumor cells of squamous cell carcinoma (SCC) and syringoma. PAR-2 was detected in primary keratinocytes and SV 40T-transformed human epidermal keratinocytes (SV-HEKs), an immortalized keratinocyte cell line, but not in SCC12 cells. SV-HEKs that were fully differentiated following calcium treatment displayed higher PAR-2 expression than undifferentiated SV-HEKs. Treatment of cultured SV-HEKs with PAR-2 agonist increased loricrin and filaggrin expression, a terminal differentiation marker. CONCLUSION: Our data suggest that PAR-2 is associated with terminal differentiation of epidermis and eccrine sweat glands. PMID- 26273150 TI - Efficacy and Safety of Calcipotriol/Betamethasone Dipropionate Ointment for the Treatment of Trachyonychia: An Open-Label Study. AB - BACKGROUND: Despite efforts to treat trachyonychia, there is no promising treatment modality. OBJECTIVE: This study evaluated the efficacy and safety of calcipotriol plus betamethasone dipropionate ointment on trachyonychia. METHODS: A total of 39 patients with 432 nails affected by trachyonychia were enrolled. All patients applied calcipotriol/betamethasone ointment once daily without occlusion for 6 months. Outcome measures were assessed by physician's global assessment (degree of roughness: 0, clear; 1, mild; 2, moderate; 3, marked; 4, severe) at all time points. RESULTS: After 6 months of therapy, 98.6% (426/432) of nails showed significant clinical improvement; 4.2% were completely free from nail lesions. The mean physician global assessment score decreased significantly from 3.5 to 1.7 points (p< 0.05). No serious side effects were reported, except mild pruritus and erythema in 2 patients. CONCLUSION: This is the first study to prospectively evaluate the efficacy and safety of calcipotriol/betamethasone ointment for the treatment of trachyonychia. The results indicate topical calcipotriol/betamethasone is an effective and safe treatment for symptom improvement of trachyonychia. PMID- 26273151 TI - Magnesium Ascorbyl Phosphate Regulates the Expression of Inflammatory Biomarkers in Cultured Sebocytes. AB - BACKGROUND: Acne is an inflammatory skin disorder caused by inflammatory biomarkers. Magnesium ascorbyl phosphate (MAP) is a stable precursor of vitamin C. It achieves a constant delivery of vitamin C into the skin and has antioxidative effects. OBJECTIVE: We performed this study to evaluate the effect of MAP on the expression of inflammatory biomarkers in cultured sebocytes. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay were performed for inflammatory cytokines and matrix metalloproteinases (MMPs) before and after treatment of cultured sebocytes with MAP (10(-2) M), lipopolysaccharide (LPS) (5 ug/ml) and a combination of MAP and LPS. RT-PCR and western blotting were also performed for antimicrobial peptides (AMPs) and Toll-like receptor (TLR)-4 before and after treatment of cultured sebocytes with MAP, LPS, and a combination of MAP and LPS. Quantification of lipid peroxidation was also conducted. RESULTS: The increased expression of inflammatory cytokines after treatment of cultured sebocytes with LPS was decreased after treatment with MAP. MMPs, AMPs, and TLR-4 were decreased after treatment of cultured sebocytes with MAP and a combination of MAP and LPS, and increased after treatment of cultured sebocytes with LPS alone. Lipid peroxidation was significantly decreased after treatment of cultured sebocytes with MAP and a combination of MAP and LPS. MAP decreased the increased lipid peroxidation after treatment of cultured sebocytes with LPS. CONCLUSION: MAP may be an effective alternative agent to improve inflammatory reactions in acne. PMID- 26273152 TI - A Family-Engaged Educational Program for Atopic Dermatitis: A Seven-Year, Multicenter Experience in Daegu-Gyeongbuk, South Korea. AB - BACKGROUND: It is important to educate families of pediatric patients with atopic dermatitis (AD) so that they have a correct understanding of AD. OBJECTIVE: The purpose of this study is to introduce, evaluate, and improve our family-engaged educational program. METHODS: Children suffering from AD and their families have participated in a half-day educational program called "AD school" with catchy slogans such as "Enjoy with AD Families!" every year since 2005. Educational lectures were conducted for parents. For children with AD, various entertaining programs were provided. A feedback survey about AD school was administered for the purpose of evaluation. RESULTS: A total of 827 people (376 patients and 451 family members) participated in this program over 7 years. On-site surveys showed a positive response (i.e., "excellent" or "good") for the prick test (95.1%), emollient education (78.4%), educational lecture (97.0%), drawing contest and games (90.2%), and recreation (magic show; 99.0%) respectively. Telephone surveys one year later also elicited a positive response. CONCLUSION: We herein introduce the experience of a half-day, family-engaged educational program for AD. Family engaged education programs for AD such as this AD school encourage and validate family participation in the treatment of their children's AD. PMID- 26273153 TI - Patch Testing with Dental Screening Series in Oral Disease. AB - BACKGROUND: The oral mucosa is constantly exposed to several irritants and allergens including dental materials, but the role of contact allergy in oral disease is obscure. OBJECTIVE: To analyze positive patch test results in patients with oral diseases and evaluate the clinical relevance of oral diseases with contact allergy to dental materials. METHODS: We retrospectively analyzed patch test results with dental screening series in 44 patients with oral disease from 2004~2011. RESULTS: Oral diseases included oral lichen planus (54.5%), cheilitis (27.3%), burning mouth syndrome (9.1%), and others (9.1%). Thirty-one of 44 patients (70.5%) had positive reactions to one or more allergens. The most commonly detected allergens were gold sodium thiosulfate (25.0%) and nickel sulfate (25.0%), followed by potassium dichromate (22.7%), cobalt (15.9%), palladium (6.8%), mercury (4.5%), copper (4.5%), and methylhydroquinone (4.5%). Six of 24 patients with oral lichen planus had a symptom in areas adjacent to dental materials and positive patch test reactions to allergens contained in the suspected dental materials. CONCLUSION: Patch tests with dental screening series are worth considering for oral diseases, especially for oral lichen planus. PMID- 26273154 TI - Button Osteoma: A Review of Ten Cases. AB - BACKGROUND: Button osteoma presents as small circumscribed ivory-like lumps on the skull vault. Although not rare, its diagnosis can be challenging for dermatologists. OBJECTIVE: To clarify the clinical characteristics of button osteoma by reviewing 10 cases. METHODS: Ten patients diagnosed with button osteoma at the Department of Dermatology, Kyungpook National University Hospital, between January 2011 and August 2014 were enrolled. We retrospectively reviewed medical records and analyzed demographic and clinical characteristics including sex, age, sites, number of lesions, symptoms, duration, histopathological finding, radiological findings, and treatment. RESULTS: All patients presented with an asymptomatic small circumscribed hard lump fixed to a bony structure. There were 9 female and 1 male patient, and the mean age was 54 years (range, 28~61 years). The most common site was the forehead, and disease duration ranged from 2 weeks to more than 20 years. The differential diagnosis included cranial exostosis, ballooned osteoma, epidermal cyst, and lipoma. Simple radiography, ultrasonography, and computed tomography (CT) were used to make a confirmative diagnosis. Histopathological findings showed lamellated bony structures with poor vascularization. Ostectomy was performed for 5 patients, and no recurrence was detected within an average of 13.4 months after treatment. CONCLUSION: This review characterized button osteoma. Surgical excision is a useful therapeutic modality after CT-based diagnosis. Further studies with more patients are required to confirm the findings. PMID- 26273155 TI - Antibiotic Susceptibility of Staphylococcus aureus in Atopic Dermatitis: Current Prevalence of Methicillin-Resistant Staphylococcus aureus in Korea and Treatment Strategies. AB - BACKGROUND: Staphylococcus aureus is a well-known microbe that colonizes or infects the skin in atopic dermatitis (AD). The prevalence of methicillin resistant S. aureus (MRSA) in AD has recently been increasing. OBJECTIVE: This study aimed to determine the antimicrobial susceptibility patterns in AD skin lesions and evaluate the prevalence of MRSA in Korea. We also recommend proper first-line topical antibiotics for Korean patients with AD. METHODS: We studied S. aureus-positive skin swabs (n=583) from the lesional skin of infants, children, and adults who presented to our outpatient clinic with AD from July 2009 to April 2012. RESULTS: S. aureus exhibited high susceptibility against most antimicrobial agents. However, it exhibited less susceptibility to benzylpenicillin, erythromycin, clindamycin, and fusidic acid. The prevalence of MRSA was 12.9% among 583 S. aureus isolates, and the susceptibility to oxacillin was significantly lower in infants in both acute and chronic AD lesions. CONCLUSION: S. aureus from AD has a high prevalence of MRSA and multidrug resistance, especially in infants. In addition, the rate of fusidic acid resistance is high among all age groups, and mupirocin resistance increases with age group regardless of lesional status. This is the first study comparing the antimicrobial susceptibility rates of S. aureus isolates from AD cases with respect to age and lesion status in Korea. PMID- 26273156 TI - Characteristics and Clinical Manifestations of Pigmented Purpuric Dermatosis. AB - BACKGROUND: Pigmented purpuric dermatoses (PPD) are a spectrum of disorders characterized by a distinct purpuric rash. Although PPD can be easily diagnosed, the disease entity remains an enigma and a therapeutic challenge. OBJECTIVE: The purpose of this study was to investigate the characteristics and clinical manifestations of PPD and to elucidate the relationship between assumed etiologic factors and the clinical manifestations of PPD and treatment responses. METHODS: Retrograde analyses were performed to identify appropriate PPD patients who visited Korea University Medical Center Anam Hospital from 2002 to 2012. RESULTS: Information on 113 patients with PPD was analyzed, and 38 subjects with skin biopsy were included for this study. Schamberg's disease was the most frequent clinical type (60.5%). Concomitant diseases included hypertension (15.8%), diabetes (10.5%), and others. Associated medication histories included statins (13.2%), beta blockers (10.5%), and others. Possibly associated etiologic factors were recent upper respiratory infection (5.3%), high orthostatic pressure due to prolonged standing (2.6%), and strenuous exercise (2.6%). A total of 36 patients (94.7%) were treated with one or more treatment methods, including oral antihistamines, pentoxifylline, topical steroids, and/or phototherapy. There was no significant difference in disease progress according to underlying diseases, medications, or association factors (p>0.05). CONCLUSION: Our overall results were grossly consistent with the existing literature, excluding several findings. Although a possible relationship between PPD and cardiovascular disease or cardiovascular medication was proposed at the beginning of the study, no statistically significant correlations were found according to the specific clinical types and treatment responses (p>0.05). PMID- 26273158 TI - Delayed Reconstruction for the Non-Amputative Treatment of Subungual Melanoma. AB - BACKGROUND: In cases of early stage subungual melanoma (SUM), conservative treatment with non-amputative wide excision of the nail unit and subsequent skin graft is preferred over amputation to preserve the involved digit. OBJECTIVE: We report a series of patients with SUM treated with conservative surgery and suggest an effective supplementary treatment process. METHODS: We retrospectively reviewed 10 patients (2 males, 8 females) who were diagnosed with in situ or minimally invasive SUM on the first biopsy and underwent non-amputative wide excision of the nail unit. All patients underwent secondary intention healing during the histopathological re-evaluation of the entire excised lesion, and additional treatment was administered according to the final report. RESULTS: In two of 10 patients, amputation was performed because of the detection of deep invasion (Breslow thickness: 4.0, 2.3 mm) from the final pathologic results, which differed from the initial biopsy. In six patients who received delayed skin graft, the mean total time required for complete healing after secondary intention healing and the skin graft was 66.83+/-15.09 days. As a result of this delayed skin graft, the final scarring was similar to the original shape of the nail unit, scored between 5 and 10 on a visual analogue scale. Most patients were satisfied with this conservative surgery except one patient, who had volar portion involvement and received an interpolated flap instead of a skin graft. CONCLUSION: Our treatment process can reduce the risk of incomplete resection and improve cosmetic outcomes in patients with SUM. PMID- 26273159 TI - Vitamin D as a Marker for Disease Severity in Chronic Urticaria and Its Possible Role in Pathogenesis. AB - BACKGROUND: Chronic urticaria is defined as repeated episodes of wheals lasting for 6 weeks or longer. Nowadays, the role of vitamin D in various chronic diseases is a matter of great interest, but limited data is available on the vitamin D status in patients with chronic urticaria. OBJECTIVE: The goal of this study was to investigate the relationship between vitamin D status and clinical characteristics of chronic urticaria. METHODS: The clinical records of 72 patients with chronic urticaria, 26 with acute urticaria and 26 with atopic dermatitis, along with 72 healthy controls, were retrospectively reviewed. RESULTS: The serum 25-(OH)D3 level was found to be significantly reduced in patients with chronic urticaria compared to those in the other groups. In particular, the proportion of patients with critically low vitamin D levels (<10 ng/ml) was significantly higher in the chronic urticaria group than in the other groups. The serum vitamin D levels showed significant negative associations with urticaria activity score and disease duration. In addition, serum vitamin D levels were significantly lower in subjects with a positive autologous serum skin test than in subjects with a negative result. CONCLUSION: In conclusion, the serum vitamin D level was more likely to be critically low in patients with chronic urticaria, and an inverse relationship with disease severity and disease duration was observed. These findings may open up the possibility of the clinical use of vitamin D as a contributing factor in the pathogenesis of chronic urticaria and a predictive marker for disease activity in chronic urticaria. PMID- 26273157 TI - Alopecia Areata in the Elderly: A 10-Year Retrospective Study. AB - BACKGROUND: Alopecia areata (AA) is an organ-specific autoimmune disease that typically occurs in young adults. AA in the elderly is relatively rare, thus little data have been reported. OBJECTIVE: This study aimed to understand the clinical characteristics of AA in the elderly. METHODS: We performed a 10-year retrospective study of AA in the elderly who visited our dermatologic clinic from January 2002 to December 2011. A clinical review of medical records and telephone interviews were performed by two dermatologists. RESULTS: Among 1,761 patients with newly diagnosed AA, 61 (3.5%) were older than 60 years at the first visit. Among those who completed a telephone interview, 74.3% (26/35) had less than 50% of scalp-localized hair loss. There was no association between the extent of AA and hair graying (p=0.679). Favorable therapeutic response was observed in 62.9% (22/35) of cases. CONCLUSION: AA in the elderly shows mild disease severity and favorable treatment response. There is no association between graying and the extent of AA. However, the influence of aging on the pathogenesis of AA in the elderly deserves further investigation. PMID- 26273160 TI - Successful Treatment of Hydroxychloroquine-Induced Recalcitrant Acute Generalized Exanthematous Pustulosis with Cyclosporine: Case Report and Literature Review. AB - Acute generalized exanthematous pustulosis (AGEP) is a cutaneous reaction principally induced by drugs. Spontaneous resolution is observed in most patients. However, severe cases required systemic corticosteroid administration. Hydroxychloroquine, which is used to treat some dermatologic and rheumatologic diseases because of its anti-inflammatory and immunosuppressive effects, is an uncommon cause of AGEP. A 67-year-old female patient presented with severe AGEP due to hydroxychloroquine treatment. She was recalcitrant to supportive care and systemic corticosteroid treatment butwas successfully treated with cyclosporine. Hydroxychloroquine-induced AGEP occurs in women with underlying rheumatologic diseases, has a longer latent period, and has a severe course usually requiring systemic treatment. PMID- 26273161 TI - Multiple Segmental Eccrine Spiradenoma with a Zosteriform Pattern: A Case Report and Literature Review. AB - Eccrine spiradenoma usually occurs as solitary tender nodules. However, it rarely occurs as multifocal localized tumors or has zosteriform distribution. We report the case of a 32-year-old woman with a 20-year history of itchy lesions on the left side of the back and forearm with a zosteriform distribution. Before disease onset, almost no patients have inducing factors, but our patient received an injection beforehand; however, whether this was coincidental or causative remains unknown. The lesions became very itchy after perspiration or eating spicy food, which has never been reported. A literature search revealed 22 cases of multiple segmental eccrine spiradenoma; we summarized the clinical characteristic in order to aid diagnosis and treatment selection. PMID- 26273162 TI - A Case of Metastatic Gastric Adenocarcinoma Mimicking Preseptal Cellulitis. AB - Cutaneous metastasis from gastric adenocarcinoma is uncommon, and the eyelid is a rare metastatic site. Three patterns of clinical presentation of eyelid metastasis have been described: nodular, infiltrative, and ulcerated. The infiltrative pattern, also known as an inflammatory diffuse pattern or mask-like metastasis, can be easily misdiagnosed as cellulitis or contact dermatitis. Here, we report a case of gastric adenocarcinoma in a 75-year-old man who presented with a localized erythematous plaque on his eyelid that developed four months earlier. The patient had been treated with an antimicrobial agent owing to suspicion of preseptal cellulitis. Gastric adenocarcinoma metastasis was diagnosed on the basis of histopathological examination and immunophenotyping (i.e., cytoplasmic epithelial membrane antigen, cytokeratin- 7, cytokeratin-20, and carcinoembryonic antigen). For patients with malignant neoplasms, persistent skin lesions similar to cellulitis or contact dermatitis should be suspected of metastasis derived from an internal malignancy, even for very rare sites of metastasis. PMID- 26273163 TI - Marjolin's Ulcer Presenting with In-Transit Metastases: A Case Report and Literature Review. AB - Marjolin's ulcer is an aggressive cutaneous malignancy common in previously traumatized or chronically inflamed skin. It has high regional metastasis and fatality rates. Our patient presented with subcutaneous nodules and ulcerations on the right limb. He had a history of osteomyelitis of the fifth toe. Histopathological examination of the nodule and ulceration demonstrated squamous cell carcinoma. The nodules and ulcerations were in-transit metastases of Marjolin's ulcer. Here, we present a case of squamous cell carcinoma arising at a site of a chronic osteomyelitis with resultant in-transit metastases. PMID- 26273165 TI - Effects of Topical N-Acetylcysteine on Skin Hydration/Transepidermal Water Loss in Healthy Volunteers and Atopic Dermatitis Patients. PMID- 26273166 TI - Acquired Perforating Osteoma Cutis. PMID- 26273167 TI - Cyclosporine-Induced Posterior Reversible Encephalopathy Syndrome in a Patient with Pemphigus Vulgaris. PMID- 26273164 TI - Erythrodermic Psoriasis Treated with Golimumab: A Case Report. AB - Erythrodermic psoriasis (EP) is a very severe variant of psoriasis whose management poses a challenge to physicians, as currently available therapies often provide unsatisfactory results. Many biologics have been used to treat chronic plaque psoriasis, the most common form of psoriasis; however, their effectiveness for EP is poorly understood. A recently developed biologic, golimumab, has been extensively studied for the treatment of moderate-to-severe active rheumatoid arthritis, psoriatic arthritis, active ankylosing spondylitis, and chronic plaque psoriasis. However, no clinical trials have been performed for EP. Here, we report the case of a 32-year-old man who presented with severe psoriasis that previously failed to respond satisfactorily to methotrexate, cyclosporine, retinoid, narrow-band ultraviolet B phototherapy, and topical agents (i.e., steroids and calcipotriol). Skin lesions worsened progressively and developed into erythroderma. Psoriatic arthritis was also detected. Conventional therapies lacked efficacy. Therefore, we administered golimumab 50 mg. The skin lesions improved significantly according to the Psoriasis Area and Severity Index score after the first administration; lesions improved further throughout the treatment course. Although additional studies are required to fully evaluate the efficacy and safety of golimumab, this agent may be an alternative treatment strategy for some patients with recalcitrant EP. PMID- 26273168 TI - Synchronous Onset of Symmetrically Associated Extragenital Lichen Sclerosus and Vitiligo on both Breasts and the Vulva. PMID- 26273169 TI - Generalized Eosinophilic Pustular Folliculitis of Infancy Responding to Hydroxyzine. PMID- 26273170 TI - A Case of Gonadotropin-Releasing Hormone Agonist-Induced Sterile Abscess Showing a Good Response to Systemic Steroid Therapy. PMID- 26273172 TI - Cefaclor-Induced Generalized Fixed Drug Eruption. PMID- 26273173 TI - A Case of Sporadic Dyschromatosis Universalis Hereditaria. PMID- 26273171 TI - Diagnostic Pitfalls of Differentiating Cellular Digital Fibroma from Superficial Acral Fibromyxoma. PMID- 26273174 TI - Mycosis Fungoides Diagnosed with an Initial Sign Resembling Benign Dermatosis on the Upper Eyelids. PMID- 26273175 TI - A Rare Case of Multiple Spindle Cell Lipomas. PMID- 26273176 TI - Mutations in EDA and EDAR Genes in a Large Mexican Hispanic Cohort with Hypohidrotic Ectodermal Dysplasia. PMID- 26273177 TI - Scleredema of Buschke Following Streptococcal Infection. PMID- 26273178 TI - Acral Angioosteoma Cutis on the Great Toe Mimicking Pyogenic Granuloma. PMID- 26273179 TI - Eccrine Chromhidrosis Resembling Clinical Features of Pompholyx with Bile-Like Greenish Pigmentation on the Right Palm and Soles. PMID- 26273180 TI - Efficient coding of natural images with a population of noisy Linear-Nonlinear neurons. AB - Efficient coding provides a powerful principle for explaining early sensory coding. Most attempts to test this principle have been limited to linear, noiseless models, and when applied to natural images, have yielded oriented filters consistent with responses in primary visual cortex. Here we show that an efficient coding model that incorporates biologically realistic ingredients - input and output noise, nonlinear response functions, and a metabolic cost on the firing rate - predicts receptive fields and response nonlinearities similar to those observed in the retina. Specifically, we develop numerical methods for simultaneously learning the linear filters and response nonlinearities of a population of model neurons, so as to maximize information transmission subject to metabolic costs. When applied to an ensemble of natural images, the method yields filters that are center-surround and nonlinearities that are rectifying. The filters are organized into two populations, with On- and Off-centers, which independently tile the visual space. As observed in the primate retina, the Off center neurons are more numerous and have filters with smaller spatial extent. In the absence of noise, our method reduces to a generalized version of independent components analysis, with an adapted nonlinear "contrast" function; in this case, the optimal filters are localized and oriented. PMID- 26273181 TI - Efficient and direct estimation of a neural subunit model for sensory coding. AB - Many visual and auditory neurons have response properties that are well explained by pooling the rectified responses of a set of spatially shifted linear filters. These filters cannot be estimated using spike-triggered averaging (STA). Subspace methods such as spike-triggered covariance (STC) can recover multiple filters, but require substantial amounts of data, and recover an orthogonal basis for the subspace in which the filters reside rather than the filters themselves. Here, we assume a linear-nonlinear-linear-nonlinear (LN-LN) cascade model in which the first linear stage is a set of shifted ('convolutional') copies of a common filter, and the first nonlinear stage consists of rectifying scalar nonlinearities that are identical for all filter outputs. We refer to these initial LN elements as the 'subunits' of the receptive field. The second linear stage then computes a weighted sum of the responses of the rectified subunits. We present a method for directly fitting this model to spike data, and apply it to both simulated and real neuronal data from primate V1. The subunit model significantly outperforms STA and STC in terms of cross-validated accuracy and efficiency. PMID- 26273182 TI - Relations of Anxiety Sensitivity, Control Beliefs, and Maternal Over-Control to Fears in Clinic-Referred Children with Specific Phobia. AB - The relations of fear to anxiety sensitivity, control beliefs, and maternal overprotection were examined in 126 7- to 13-year-old clinically referred children with specific phobias. Results indicated that anxiety sensitivity and control beliefs were significant predictors of children's fear levels, accounting for approximately 48% of the total variance. Unexpectedly, age, gender, and maternal overprotection did not emerge as significant predictors of fear in the overall sample. In subsequent analyses, anxiety sensitivity was found to be a consistent, significant predictor for both girls and boys, for both younger and older children, and for children with and without an additional anxiety disorder diagnosis. Control beliefs were only a significant predictor for girls, younger children, and children with an additional anxiety diagnosis. Maternal overprotection was not a significant predictor for any group. Children with an additional anxiety disorder diagnosis had higher levels of fear, anxiety sensitivity, and maternal overprotection, as well as lower levels of control beliefs than the non-additional anxiety disorder subgroup. Future directions and clinical implications are explored. PMID- 26273183 TI - Kindergarten Predictors of Recurring Externalizing and Internalizing Psychopathology in 3rd and 5th grade. AB - The purpose of this study was to evaluate the extent to which a range of risk factors (e.g., gender, race/ethnicity, low socioeconomic status [SES], whether the child's family had divorced or separated, low reading readiness, inattention) predicted kindergarten children's likelihood of later recurring psychopathology. Multilevel logistic regression was used to analyze teacher-ratings of frequent and recurring externalizing and internalizing problem behaviors in a longitudinal sample of 4,674 K-5th grade children participating in the Early Childhood Longitudinal Study-Kindergarten Cohort, 1998-1999. Results indicated that certain groups of kindergarten children are at higher risk. Those most at risk of displaying high levels of externalizing problem behaviors in both 3rd and 5th grade are children entering school already displaying high levels of these behaviors, as well as those displaying low reading readiness. Boys and those from low SES households are also at higher risk. Hispanics (compared to whites) are at reduced risk of such problem behaviors. Those most at risk of displaying 3rd and 5th grade recurring internalizing behavior problems are those entering kindergarten with such problems, and children displaying inattention and other learning-related behavior problems. Boys, those from low SES households, and children not being raised by both biological parents are also more likely to display recurrent internalizing behavior problems in 3rd and 5th grade. Asian children are at reduced risk of engaging in these behavior problems. PMID- 26273184 TI - Evaluating an Electronic Measure of Colorectal Cancer Screening at Indian Health Service Facilities, 2008-2010. AB - BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer mortality in American Indian and Alaska Native (AIAN) people, and incidence rates vary considerably among AIAN populations throughout the United States. Screening has the potential to prevent CRC deaths by detection and treatment of early disease or removal of precancerous polyps. Surveillance of CRC screening is critical to efforts to improve delivery of this preventive service, but existing CRC screening surveillance methods for AIAN are limited. The Government Performance and Results Act (GPRA) CRC screening clinical care measure provides data on CRC screening among AIAN populations. PURPOSE: The aim of this study was to evaluate the accuracy of the GPRA measure for CRC screening (sensitivity, specificity, positive predictive value and negative predictive value), determine reasons for CRC screening misclassification (procedures noted as screening when they were actually diagnostic exams), and to suggest opportunities for improving surveillance for CRC screening nationwide for AIAN populations. METHODS: Medical record reviews (paper and electronic) were compared to the GPRA-reported CRC screening status for 1,071 patients receiving care at tribal health facilities. A total of 8 tribal health facilities (2 small, 3 medium, and 3 large) participated in the study from the Pacific Coast, the Southwest, the Southern Plains, and Alaska IHS regions. Screening-eligible patients were identified using queries of the local electronic health record from January 2007 to December 2008, and medical chart reviews were completed at participating facilities from September 2008 to June 2010. RESULTS: Among 545 patients classified as screened by the GPRA measure, 305 (56%, CI: 52%-60%) had a false positive for screening as compared with medical record review. The overall sensitivity of the GPRA measure for CRC screening was 93% (CI=89%-95%) while specificity was 62% (CI: 59%-66%). The most common reasons for misclassification were for diagnostic or surveillance tests to be recorded as screening (67%), as well as medical record miscoding (18%) due to miscoding, charting errors, screenings performed outside the IHS, testing for a non-screening purpose, and categorization of patients as screened when a test had been ordered but not actually completed. CONCLUSIONS: This study found that the GPRA CRC screening clinical measure overestimates the true screening rate due to the inclusion of diagnostic and surveillance exams, especially colonoscopy, as well as misclassification errors. The results of this study suggest a need to more accurately use the ICD-9 diagnostic code V76.51, which was associated with frequent coding errors. In combination with other programmatic efforts that focus on screening average- risk, asymptomatic American Indian and Alaska Native persons, improving the coding used for CRC screening may help to more accurately detect decreases in AIAN CRC incidence and mortality. PMID- 26273185 TI - Early Diagnosis of Colonic Anastomotic Leak With Peritoneal Endoscopy. AB - BACKGROUND AND OBJECTIVES: At present, we do not have a reliable method for the early diagnosis of colorectal anastomotic leakage (AL). We tested peritoneal flexible endoscopy through a port placed in the abdominal wall in the early postoperative course, as a new diagnostic method for detection of this complication and evaluated the suggested method for safety, feasibility, and accuracy. METHODS: Ten swine were randomized into 2 groups: group A, colorectal anastomosis without leakage; and group B, colorectal anastomosis with leakage. A button gastrostomy feeding tube was inserted percutaneously into the peritoneal cavity. Colorectal anastomosis (with or without defect) was created 48 hours after the first operation. The swine were examined by peritoneal flexible endoscopy 8 and 24 hours after the colonic operation, by a consultant surgeon who was blinded to both the presence and the allocated location of the of the anastomotic defect. RESULTS: None of the animals showed signs of illness 48 hours after the intraperitoneal gastrostomy tube placement. More than half of the anastomosis circumference was identified in 60 and 10% of the animals at endoscopy 8 and 24 hours, respectively, after the anastomosis was created. Excessive adhesion formation was observed in all animals, irrespective of AL. The sensitivity and specificity of endoscopy in detecting peritonitis 24 hours after AL were both 60%. CONCLUSIONS: Peritoneal endoscopy is a safe and simple procedure. Visualization of the peritoneal cavity in the early postoperative course was limited due to adhesion formation. Further studies are needed to clarify the accuracy of the procedure and to address additional methodological concerns. PMID- 26273187 TI - Self-Reported Mental Health Predicts Acute Respiratory Infection. AB - BACKGROUND: Poor mental health conditions, including stress and depression, have been recognized as a risk factor for the development of acute respiratory infection. Very few studies have considered the role of general mental health in acute respiratory infection occurrence. The aim of this analysis is to determine if overall mental health, as assessed by the mental component of the Short Form 12 Health Survey, predicts incidence, duration, or severity of acute respiratory infection. METHODS: Data utilized for this analysis came from the National Institute of Health-funded Meditation or Exercise for Preventing Acute Respiratory Infection (MEPARI) and MEPARI-2 randomized controlled trials examining the effects of meditation or exercise on acute respiratory infection among adults aged > 30 years in Madison, Wisconsin. A Kendall tau rank correlation compared the Short Form 12 mental component, completed by participants at baseline, with acute respiratory infection incidence, duration, and area-under-the-curve (global) severity, as assessed by the Wisconsin Upper Respiratory Symptom Survey. RESULTS: Participants were recruited from Madison, Wis, using advertisements in local media. Short Form 12 mental health scores significantly predicted incidence (P = 0.037) of acute respiratory infection, but not duration (P = 0.077) or severity (P = 0.073). The Positive and Negative Affect Schedule (PANAS) negative emotion measure significantly predicted global severity (P = 0.036), but not incidence (P = 0.081) or duration (P = 0.125). Mindful Attention Awareness Scale scores significantly predicted incidence of acute respiratory infection (P = 0.040), but not duration (P = 0.053) or severity (P = 0.70). The PHQ-9, PSS-10, and PANAS positive measures did not show significant predictive associations with any of the acute respiratory infection outcomes. CONCLUSION: Self-reported overall mental health, as measured by the mental component of Short Form 12, predicts acute respiratory infection incidence. PMID- 26273186 TI - Current Trends in Laparoscopic Ventral Hernia Repair. AB - BACKGROUND AND OBJECTIVES: The purpose of this study was to analyze the surgical technique, postoperative complications, and possible recurrence after laparoscopic ventral hernia repair (LVHR) in comparison with open ventral hernia repair (OVHR), based on the international literature. DATABASE: A Medline search of the current English literature was performed using the terms laparoscopic ventral hernia repair and incisional hernia repair. CONCLUSIONS: LVHR is a safe alternative to the open method, with the main advantages being minimal postoperative pain, shorter recovery, and decreased wound and mesh infections. Incidental enterotomy can be avoided by using a meticulous technique and sharp dissection to avoid thermal injury. PMID- 26273188 TI - Colon-targeted delivery of piceatannol enhances anti-colitic effects of the natural product: potential molecular mechanisms for therapeutic enhancement. AB - Piceatannol (PCT), an anti-colitic natural product, undergoes extensive Phase II hepatic metabolism, resulting in very low bioavailability. We investigated whether colon-targeted delivery of PCT could enhance anti-colitic effects and how therapeutic enhancement occurred at the molecular level. Molecular effects of PCT were examined in human colon carcinoma cells and inflamed colons. The anti colitic effects of PCT in a colon-targeted capsule (colon-targeted PCT) were compared with PCT in a gelatin capsule (conventional PCT) in a trinitrobenzene sulfonic acid-induced rat colitis model. Colon-targeted PCT elicited greatly enhanced recovery of the colonic inflammation. In HCT116 cells, PCT inhibited nuclear factor kappaB while activating anti-colitic transcription factors, nuclear factor-erythroid 2 (NF-E2) p45-related factor 2, and hypoxia-inducible factor-1. Colon-targeted PCT, but not conventional PCT, modulated production of the target gene products of the transcription factors in the inflamed colonic tissues. Rectal administration of PCT, which simulates the therapeutic action of colon-targeted PCT, also ameliorated rat colitis and reproduced the molecular effects in the inflamed colonic tissues. Colon-targeted delivery increased therapeutic efficacy of PCT against colitis, likely resulting from multitargeted effects exerted by colon-targeted PCT. The drug delivery technique may be useful for therapeutic optimization of anti-colitic lead compounds including natural products. PMID- 26273189 TI - Emerging treatment options to improve cardiovascular outcomes in patients with acute coronary syndrome: focus on losmapimod. AB - Each year, despite optimal use of recommended acute and secondary prevention therapies, 4%-5% of patients with acute coronary syndrome (ACS) experience relapse of ACS or other cardiovascular events including stroke, heart failure, or sudden cardiac death after the index ACS. The sudden atherosclerotic plaque rupture leading to an ACS event is often accompanied by inflammation, which is thought to be a key pathogenic pathway to these excess cardiovascular events. Losmapimod is a novel, oral p38 mitogen-activated protein kinase (MAPK) inhibitor that targets MAPKs activated in macrophages, myocardium, and endothelial cells that occur as a part of global coronary vascular inflammation following plaque rupture. This review aims to 1) discuss the pathophysiological pathways through which p38 MAPKs may play key roles in initiation and progression of inflammatory disease and how losmapimod is thought to counteract these p38 MAPKs, and 2) to describe the efficacy and safety data for losmapimod obtained from preclinical studies and randomized controlled trials that support the hypothesis that it has promise as a treatment for patients with ACS. PMID- 26273190 TI - Hidden costs of antiretroviral treatment: the public health efficiency of drug packaging. AB - While the overall percentage of unused antiretroviral medicines returned to the hospital pharmacy is low, their cost is quite high. Adverse events, treatment failure, pharmacokinetic interactions, pregnancy, or treatment simplification are common reasons for unplanned treatment changes. Socially inefficient antiretroviral packages prevent the reuse of drugs returned to the hospital pharmacy. We defined antiretroviral package categories based on the excellence of drug packaging and analyzed the number of pills and costs of drugs returned during a period of 1 year in a hospital-based HIV unit attending to 2,413 treated individuals. A total of 6,090 pills (34% of all returned antiretrovirals) - with a cost of 47,139.91 ? - would be totally lost, mainly due to being packed up in the lowest efficiency packages. Newer treatments are packaged in low-excellence categories of packages, thus favoring the maintenance of these hidden costs in the near future. Therefore, costs of this low-efficiency drug packaging, where medication packages are started but not completed, in high-cost medications are substantial and should be properly addressed. Any improvement in the packaging by the manufacturer, and favoring the choice of drugs supplied through efficient packages (when efficacy, toxicity, and convenience are similar), should minimize the treatment expenditures paid by national health budgets. PMID- 26273191 TI - Randomized, open-label, blinded-endpoint, crossover, single-dose study to compare the pharmacodynamics of torasemide-PR 10 mg, torasemide-IR 10 mg, and furosemide IR 40 mg, in patients with chronic heart failure. AB - PURPOSE: Diuretics are the primary treatment for the management of chronic heart failure (HF) symptoms and for the improvement of acute HF symptoms. The rate of delivery to the site of action has been suggested to affect diuretic pharmacodynamics. The main objective of this clinical trial was to explore whether a prolonged release tablet formulation of torasemide (torasemide-PR) was more natriuretically efficient in patients with chronic HF compared to immediate release furosemide (furosemide-IR) after a single-dose administration. Moreover, the pharmacokinetics of torasemide-PR, furosemide-IR, and torasemide-IR were assessed in chronic HF patients as well as urine pharmacodynamics. METHODS: Randomized, open-label, blinded-endpoint, crossover, and single-dose Phase I clinical trial with three experimental periods. Torasemide-PR and furosemide-IR were administered as a single dose in a crossover fashion for the first two periods, and torasemide-IR 10 mg was administered for the third period. Blood and urine samples were collected at fixed timepoints. The primary endpoint was the natriuretic efficiency after administration of torasemide-PR and furosemide-IR, defined as the ratio between the average drug-induced natriuresis and the average drug recovered in urine over 24 hours. RESULTS: Ten patients were included and nine completed the study. Here, we present the results from nine patients. Torasemide-PR was more natriuretically efficient than furosemide-IR (0.096 +/- 0.03 mmol/MUg vs 0.015 +/- 0.0007 mmol/MUg; P < 0.0001). Mictional urgency was lower and more delayed with torasemide-PR than with furosemide-IR. CONCLUSION: In a study with a limited sample size, our results suggest that 10 mg of torasemide PR is more natriuretically efficient than 40 mg of furosemide-IR after single dose administration in patients with chronic HF over a 24-hour collection period. Further studies are necessary to evaluate potential pharmacodynamic differences between torasemide formulations and to assess its impact on clinical therapeutics. PMID- 26273192 TI - The role of taxanes in triple-negative breast cancer: literature review. AB - Breast cancer (BC) is the most frequent tumor worldwide. Triple-negative BCs are characterized by the negative estrogen and progesterone receptors and negative HER2, and represent 15% of all BCs. In this review, data on the use of taxanes in triple-negative BCs are analyzed, concluding they are effective in any clinical setting (neoadjuvant, adjuvant, and metastatic). Further, the role of nab paclitaxel (formulation of albumin-bound paclitaxel) in these tumors is also evaluated. The available data show the clinical potential of nab-paclitaxel based combinations in terms of long-duration response, increased survival, and better quality of life of patients with triple-negative metastatic BC. The ongoing trials will give further information on the better management of this type of tumor. PMID- 26273193 TI - Characterization of preclinical in vitro and in vivo pharmacokinetics properties for KBP-7018, a new tyrosine kinase inhibitor candidate for treatment of idiopathic pulmonary fibrosis. AB - KBP-7018 is a novel selective tyrosine kinase inhibitor with potential for the treatment of idiopathic pulmonary fibrosis. The objective of this study was to characterize the preclinical pharmacokinetics of KBP-7018 in vitro and in vivo, and then to assess the likelihood of developing KBP-7018 as a clinical candidate. The systemic clearance (CL) of KBP-7018 was relatively low in rodents and monkeys with a value of less than 30% of hepatic blood flow, while it was high in dogs. The steady-state volume of distribution (V ss) ranged from 1.51 L/kg to 4.65 L/kg across the species tested. The maximum concentration (C max) of KBP-7018 occurred at 0.25-6 hours after oral dosing, and the bioavailability was moderate (21% 68%). The human CL (~20% of hepatic blood flow) and V ss (1.6-5.3 L/kg) were predicted by allometric scaling method and together with the other modeling methods indicated low metabolism and acceptable half-time (4.8-19.3 hours) in vivo. Overall, the preclinical data make it amenable to further oral solid dosage from design for the upcoming Phase I trials in human. PMID- 26273194 TI - Modeling the longitudinal latent effect of pregabalin on self-reported changes in sleep disturbances in outpatients with generalized anxiety disorder managed in routine clinical practice. AB - BACKGROUND: Anxiety disorders are among the most common psychiatric illnesses, with generalized anxiety disorder (GAD) being one of the most common. Sleep disturbances are highly prevalent in GAD patients. While treatment with pregabalin has been found to be associated with significant improvement in GAD related sleep disturbance across many controlled clinical trials, mediational analysis has suggested that a substantial portion of this effect could be the result of a direct effect of pregabalin. Thus, the objective of this study was to model the longitudinal latent effect of pregabalin or usual care (UC) therapies on changes in sleep in outpatients with GAD under routine clinical practice. METHODS: Male and female GAD outpatients, aged 18 years or above, from a 6-month prospective noninterventional trial were analyzed. Direct and indirect effects of either pregabalin or UC changes in anxiety symptoms (assessed with Hamilton Anxiety Scale) and sleep disturbances (assessed with Medical Outcomes Study-Sleep Scale [MOS-S]) were estimated by a conditional latent curve model applying structural equation modeling. RESULTS: A total of 1,546 pregabalin-naive patients were analyzed, 984 receiving pregabalin and 562 UC. Both symptoms of anxiety and sleep disturbances were significantly improved in both groups, with higher mean (95% confidence interval) score reductions in subjects receiving pregabalin: 15.9 (-15.2; -16.6) vs -14.5 (-13.5; -15.5), P=0.027, in Hamilton Anxiety Scale; and -29.7 (-28.1; -31.3) vs -24.0 (-21.6; -26.4), P<0.001, in MOS-S. The conditional latent curve model showed that the pregabalin effect on sleep disturbances was significant (gamma =-3.99, P<0.001), after discounting the effect on reduction in anxiety symptoms. A mediation model showed that 70% of the direct effect of pregabalin on sleep remained after discounting the mediated effect of anxiety improvement. CONCLUSION: A substantial proportion of the incremental improvements in anxiety-related sleep disturbances with pregabalin vs UC were explained by its direct effect, not mediated by improvements in anxiety symptoms. PMID- 26273195 TI - The pitfall of the transient, inconsistent anticancer capacity of antiestrogens and the mechanism of apparent antiestrogen resistance. AB - Although antiestrogens have been available for breast cancer therapy since the early 1970s, neither their inconsistent anticancer capacity nor the developing antiestrogen resistance of tumors can be fully understood. Although clinical and experimental investigations revealed many tiny details concerning the link between estrogen signaling and tumor development, they yielded fairly controversial findings. Estrogen receptor (ER) overexpression in tumor cells induced by estrogen treatment was erroneously regarded as a promoter of DNA damage, genomic instability, and tumor growth. Similarly, compensatory ER overexpression caused by antiestrogen treatment or estrogen withdrawal was mistakenly evaluated as a key for rapid tumor growth attributed to acquired antiestrogen resistance. Nevertheless, ER upregulation induced by estrogen treatment is a physiologic process even in tumor cells, whereas in the case of antiestrogen administration, it is a contraregulatory action to defend the endangered estrogen signaling. Upregulation of estrogen signaling displays a unique dichotomy, ensuring the survival and safe proliferative activity of healthy cells, while inducing apoptotic death of malignant tumor cells. Analysis of the fairly controversial results justifies that whatever type of available endocrine therapies may be used, including estrogen, antiestrogen treatment, or oophorectomy, an extreme upregulation of ER signaling seems to be the crucial mechanism of successful prevention and treatment for breast cancer. The inconsistent therapeutic effects of antiestrogen administration may be explained by the different genetic capacities of patients for the compensatory upregulation of ER and aromatase enzyme expressions. The weaker the defensive counteraction against the inhibition of estrogen signaling, the poorer is the prognosis of the disease. De novo or acquired antiestrogen resistance of tumors may be associated with the missing capacity of patients for the extreme upregulation of estrogen signaling or with the exhaustion of defensive counteractions in cases that previously showed good reactivity. High-dose estrogen treatment is capable of restoring ER signaling and anticancer capacity even after heavy exposure to antiestrogen therapy. PMID- 26273197 TI - Erratum: Itraconazole solid dispersion prepared by a supercritical fluid technique: preparation, in vitro characterization, and bioavailability in beagle dogs [Corrigendum]. PMID- 26273196 TI - Gamma scintigraphic evaluation of floating gastroretentive tablets of metformin HCl using a combination of three natural polymers in rabbits. AB - The present research was aimed at formulating a metformin HCl sustained-release formulation from a combination of polymers, using the wet granulation technique. A total of 16 formulations (F1-F16) were produced using different combinations of the gel-forming polymers: tamarind kernel powder, salep (palmate tubers of Orchis morio), and xanthan. Post-compression studies showed that there were no interactions between the active drug and the polymers. Results of in vitro drug release studies indicated that the F10 formulation which contained 5 mg of tamarind kernel powder, 33.33 mg of xanthan, and 61.67 mg of salep could sustain a 95% release in 12 hours. The results also showed that F2 had a 55% similarity factor with the commercial formulation (C-ER), and the release kinetics were explained with zero order and Higuchi models. The in vivo study was performed in New Zealand White rabbits by gamma scintigraphy; the F10 formulation was radiolabeled using samarium (III) oxide ((153)Sm2O3) to trace transit of the tablets in the gastrointestinal tract. The in vivo data supported the retention of F10 formulation in the gastric region for 12 hours. In conclusion, the use of a combination of polymers in this study helped to develop an optimal gastroretentive drug-delivery system with improved bioavailability, swelling, and floating characteristics. PMID- 26273198 TI - The role of aflibercept in the management of diabetic macular edema. AB - Diabetic macular edema (DME) represents one of the leading causes of visual impairment in working-age adults. Although there are several proven treatments available for this condition, pharmacotherapy through the use of intravitreal antivascular endothelial growth factor agents has revolutionized the management of DME over the past decade with superior outcomes compared to laser therapy. This review summarizes the pathophysiology and available treatment options for the management of DME, with an emphasis on the efficacy and safety profile of a single particular intravitreal antivascular endothelial growth factor agent, aflibercept. PMID- 26273200 TI - Recruiting older patients with peripheral arterial disease: evaluating challenges and strategies. AB - Peripheral arterial disease (PAD) is a group of syndromes characterized by chronic and progressive atherosclerosis with a high burden of physical disability and cardiovascular morbidity and mortality. Recruiting patients for clinical research is therefore challenging. In this article, we describe and evaluate our methods for recruiting participants for a cross-sectional feasibility study of PAD, nutritional status, and body composition. We used convenience and purposive sampling approaches to identify potential participants. Between May 2012 and April 2013, 1,446 patients were identified, and 165 patients (11.4%) responded to recruitment requests. The final enrollment was 64 participants (64/1,446; 4.4%), and four subjects (6.3%) subsequently withdrew from the study. Recruiting PAD patients presents a variety of challenges, due largely to the burdens of living with coexistent illnesses, and patients' reluctance or inability to travel for research. In this article, we delineate suggestions for improving the efficacy of recruitment methods in future PAD studies. PMID- 26273199 TI - High-throughput virtual screening with e-pharmacophore and molecular simulations study in the designing of pancreatic lipase inhibitors. AB - BACKGROUND: Obesity is a progressive metabolic disorder in the current world population, and is characterized by the excess deposition of fat in the adipose tissue. Pancreatic lipase is one of the key enzymes in the hydrolysis of triglycerides into monoglycerides and free fatty acids, and is thus considered a promising target for the treatment of obesity. The present drugs used for treating obesity do not give satisfactory results, and on prolonged usage result in severe side effects. In view of the drastic increase in the obese population day-to-day, there is a greater need to discover new drugs with lesser side effects. MATERIALS AND METHODS: High-throughput virtual screening combined with e pharmacophore screening and ADME (absorption, distribution, metabolism, and excretion) and PAINS (pan-assay interference compounds) filters were applied to screen out the ligand molecules from the ZINC natural molecule database. The screened molecules were subjected to Glide XP docking to study the molecular interactions broadly. Further, molecular dynamic simulations were used to validate the stability of the enzyme-ligand complexes. Finally, the molecules with better results were optimized for in vitro testing. RESULTS: The screening protocols identified eight hits from the natural molecule database, which were further filtered through pharmacological filters. The final four hits were subjected to extra precision docking, and the complexes were finally studied with molecular dynamic simulations. The results pointed to the zinc 85893731 molecule as the most stable in the binding pocket, producing consistent H-bond interaction with Ser152 (G=-7.18). The optimized lead molecule exhibited good docking score, better fit, and improved ADME profile. CONCLUSION: The present study specifies zinc 85893731 as a lead molecule with higher binding score and energetically stable complex with pancreatic lipase. This lead molecule, along with its various analogs, can be further tested as a novel inhibitor against pancreatic lipase using in vitro protocols. PMID- 26273201 TI - Shared decision-making in the People's Republic of China: current status and future directions. AB - BACKGROUND: Severe insufficiencies in the supply and inequities in the distribution of health care professionals, facilities, and services create conditions for limited quality of care and lack of trust - even violent conflict between clinicians and patients in the People's Republic of China. Alongside structural reform, shared decision-making (SDM) may help meet the needs and advance the goals of each patient. Little is known, however, about the realities and opportunities for SDM in the People's Republic of China. METHODS: To identify reports of SDM in the People's Republic of China, we used multiple sources, including: several databases, searched in English and Chinese, online journals, and clinical trial registries. In addition, we contacted experts in the field to identify any articles missed through our other search strategies. We included all trials and surveys reporting on SDM in Chinese patients. We summarized these studies by describing them with particular attention to reports of patient decisional preference and of the impact of SDM interventions on outcomes in Chinese patients. RESULTS: We identified five surveys examining patient preference for SDM and nine studies examining constructs related to SDM in Chinese patients, but none involving patients in Mainland China. We could not find any reports of development, testing, or implementation of SDM tools for patients in Mainland China. CONCLUSION: The research on SDM in the People's Republic of China is limited, with almost no direct evidence to inform clinical policies or implementation. Although multiple barriers are apparent, the value of implementing, testing, and disseminating effective SDM in the People's Republic of China in terms of patient experience and outcomes demands urgent realization. PMID- 26273203 TI - The impact of nocturnal disturbances on daily quality of life in patients with Parkinson's disease. AB - OBJECTIVES: The aims of this study were to explore nocturnal disturbances in patients with Parkinson's disease (PD) and to assess their impact on quality of life (QoL). METHODS: A total of 211 patients with PD were recruited for this study, and each participant was evaluated using the mini-mental state examination, PD sleep scale - second version (PDSS-2), pittsburgh sleep quality index (PSQI), PD QoL questionnaire (PDQ), Epworth sleepiness scale, Hoehn and Yahr (H&Y) staging, and unified Parkinson's disease rating scale (UPDRS). Multiple regression analyses were performed to determine the contribution of the predictive variables on QoL. RESULTS: There were 56.4% males (mean age: 64.08 years; disease duration: 6.02 years; H&Y stage: 2.25; and UPDRS: 33.01) in this study. Our patients' actual sleep time was 5.96+/-1.16 hours and the average sleep efficiency was 82.93%+/-12.79%. Up to 64.4% of patients were classified as "poor" sleepers and 23.8% suffered from daytime sleepiness. The final stepwise regression model revealed that UPDRS parts I and II, the sleep disturbance and daytime dysfunction components of the PSQI, the PD symptoms at night subscale of the PDSS-2, and the levodopa equivalent dose were significant predictors of the PDQ score (R (2)=53, F 7,165=28.746; P<0.001). CONCLUSION: Most of the PD patients have sleep problems, and nearly one-quarter of them have abnormal daytime somnolence. The nocturnal disturbances were found to result in worse QoL in PD patients. Ethnicity-specific effects of susceptibility to sleep disturbances were discussed, and these results also highlighted the direction for further studies to explore when examining effective management programs toward these disturbances. PMID- 26273202 TI - Rare and very rare adverse effects of clozapine. AB - Clozapine (CLZ) is the drug of choice for the treatment of resistant schizophrenia; however, its suitable use is limited by the complex adverse effects' profile. The best-described adverse effects in the literature are represented by agranulocytosis, myocarditis, sedation, weight gain, hypotension, and drooling; nevertheless, there are other known adverse effects that psychiatrists should readily recognize and manage. This review covers the "rare" and "very rare" known adverse effects of CLZ, which have been accurately described in literature. An extensive search on the basis of predefined criteria was made using CLZ and its combination with adverse effects as keywords in electronic databases. Data show the association between the use of CLZ and uncommon adverse effects, including ischemic colitis, paralytic ileus, hematemesis, gastroesophageal reflux disease, priapism, urinary incontinence, pityriasis rosea, intertriginous erythema, pulmonary thromboembolism, pseudo pheochromocytoma, periorbital edema, and parotitis, which are influenced by other variables including age, early diagnosis, and previous/current pharmacological therapies. Some of these adverse effects, although unpredictable, are often manageable if promptly recognized and treated. Others are serious and potentially life-threatening. However, an adequate knowledge of the drug, clinical vigilance, and rapid intervention can drastically reduce the morbidity and mortality related to CLZ treatment. PMID- 26273204 TI - A role of Yueju in fast-onset antidepressant action on major depressive disorder and serum BDNF expression: a randomly double-blind, fluoxetine-adjunct, placebo controlled, pilot clinical study. AB - INTRODUCTION: Conventional antidepressants, including fluoxetine, have a major disadvantage in delayed onset of efficacy. Yueju, an herbal medicine used to treat mood disorders was recently found to exhibit rapid antidepressant effects. The present study was conducted to evaluate the role of Yueju in rapidly acting on major depressive disorder (MDD). METHODS: Participants were MDD patients with scores of 24-item Hamilton Depression Rating Scale (HDRS-24) >=20 and without history of antidepressant use. They randomly received daily oral doses of Yueju (23 g/day) plus fluoxetine (20 mg/day) (experimental group) or placebo plus fluoxetine (control group) for 7 days. HDRS-24 was used as the primary outcome measurement at baseline, and on days 1, 3, 5, and 7. Concentrations of serum brain-derived neurotrophic factor (BDNF) were assessed at baseline and on days 1 and 7. RESULTS: In all, 18 participants met the criteria for data analysis. Compared to baseline level, only experimental group showed significant decrease of HDRS-24 score from day 3 to day 7 (P<0.05). Experimental group also showed significant improvement compared with control group from day 3 to day 7 (P<0.05). No correlation between treatment outcomes with serum BDNF levels was observed. However, experimental group showed significant correlation for serum BDNF level on day 1 with day 7 (r=0.721, P=0.028), whereas the control group did not. CONCLUSION: Yueju likely contributes to fast-onset antidepressant effects on MDD. Further investigation is necessary to firmly establish the ancient formula as a safe, efficacious, and rapidly acting alternative medicine for MDD treatment. PMID- 26273206 TI - Associations between deepness of response and clinical outcomes among Japanese patients with metastatic colorectal cancer treated with second-line FOLFIRI plus cetuximab. AB - BACKGROUND: In the FIRE-3 trial, overall survival (OS) was significantly longer in patients treated with FOLFIRI plus cetuximab (C-mab) than in those treated with FOLFIRI plus bevacizumab (Bev), but progression-free survival (PFS) was not significantly different. This may be associated with the deepness of response (DpR) in patients treated with FOLFIRI plus C-mab. We aimed to evaluate the relationship between clinical outcome and DpR in metastatic colorectal cancer (mCRC) patients treated with second-line FOLFIRI plus C-mab. METHODS: A total of 112 patients with histopathologically confirmed mCRC treated with second-line FOLFIRI in combination with C-mab (N=42) or Bev (N=70) were retrospectively enrolled between October 2008 and June 2013. The relationship between DpR and clinical outcome in patients treated with FOLFIRI plus C-mab or Bev was determined. RESULTS: Forty-two patients treated with FOLFIRI plus C-mab had a mean DpR of 6.1% (inter-quartile range: -13.7%, 20.8%) and a minimum DpR of 62.7%. On the other hand, 70 patients treated with FOLFIRI plus Bev had a mean DpR of 0% (interquartile range: -16%, 10%) and a minimum DpR of -111%. DpR >=30% was associated with significantly longer OS and PFS when compared with DpR <=30% in patients given FOLFIRI plus C-mab. DpR (>=30%) was independently associated with prolongation of OS and PFS. In patients treated with FOLFIRI plus C-mab, there was a moderate positive correlation between DpR and clinical outcomes (OS: r=0.51, P<0.001; PFS: r=0.54, P<0.001). CONCLUSION: FOLFIRI plus C-mab yielded a stronger correlation between DpR and clinical outcomes. These results indicate the potential of DpR as a new measure of efficacy in mCRC patients treated with second-line chemotherapy plus C-mab. PMID- 26273205 TI - Pain perception in schizophrenia: influence of neuropeptides, cognitive disorders, and negative symptoms. AB - OBJECTIVES: The causes and nature of insensitivity to pain in schizophrenia remain unknown. The role of endorphins and the association of cognitive dysfunction and negative symptoms are postulated. METHODS: In this study, 43 patients with schizophrenia, five first-degree relatives, and 34 healthy controls were examined. Participants' plasma concentrations of substance P, beta endorphin, and calcitonin gene-related peptide (CGRP) were assessed. In patients, the Trail-Making Test, the Color Reading Interference Test (Stroop test), and the Positive and Negative Syndrome Scale Negative Syndrome subscale (PANSS N) test were performed. We also evaluated pain threshold using nociceptive reflex (RTIII) testing. RESULTS: The mean beta-endorphin concentration was about 20% higher in patients than in healthy controls (P<0.05). CGRP concentrations were significantly higher in patients than in controls (5.34 ng/mL versus 4.16 ng/mL; P<0.01). Subjects treated with antipsychotic polytherapy had higher concentrations of CGRP than did patients treated with second-generation antipsychotic monotherapy (5.92 ng/mL versus 5.02 ng/mL; P<0.05). There were no correlations between any biochemical parameters and Trail-Making Test, Stroop test, and PANSS N scores. There were no differences in RTIII among study groups. Strong negative correlation (P<0.001) was found between PANSS N scores and subjective pain threshold on the right lower limb. CONCLUSION: The insensitivity to pain in schizophrenia is a complex phenomenon that is probably not related to changes in nociceptive pathways. Increase in beta-endorphin level may be related to this issue, but it is uncertain if such concentration ensures analgesic effect. It is unknown if patients with schizophrenia in fact experience less pain. Cognitive impairment and excess negative symptoms may strongly influence the patient's expression of pain. PMID- 26273207 TI - Nivolumab in the treatment of malignant melanoma: review of the literature. AB - Nivolumab was developed as a monoclonal antibody against programmed death receptor-1, an immune checkpoint inhibitor which negatively regulates T-cell proliferation and activation. Intravenous administration of nivolumab was approved for the treatment of unresectable malignant melanoma in 2014 in Japan. When advanced melanoma patients were treated with nivolumab, median overall survival became longer. Overall survival rate was significantly better in nivolumab-treated melanoma patients than dacarbazine-treated melanoma patients. Nivolumab had an acceptable long-term tolerability profile, with 22% of patients experiencing grade 3 or 4 adverse events related to the drug. Therefore, nivolumab can become an alternative therapy for advanced malignant melanoma. PMID- 26273209 TI - Bridging the Gap: A Regulator of NF-kappaB Linking Inflammation and Cancer. AB - BACKGROUND: A close connection between inflammation and cancer has now been firmly established. While tumor initiation is typically independent of inflammatory events, immune cells infiltrating the tumor microenvironment secrete inflammatory cytokines that enhance the aberrant growth of tumor cells and thus facilitate tumor progression. Therefore, inflammation and tumor growth are usually interpreted as closely related on a systemic level but as distinct, independently regulated processes at a molecular level. HIGHLIGHT: Recently, we reported that a sub-class of small GTPases, namely kappaB-Ras1 and kappaB-Ras2, regulate both inflammation and tumor growth, thereby providing a unique molecular bridge between the two biological processes. CONCLUSION: Here, we briefly summarize the known contact points between inflammation and cancer, including oral cancers, and put into context the identification of kappaB-Ras proteins as molecular link between two independent pathways important for tumor growth. PMID- 26273208 TI - Phytochemicals modulate carcinogenic signaling pathways in breast and hormone related cancers. AB - Over the years, nutrition and environmental factors have been demonstrated to influence human health, specifically cancer. Owing to the fact that cancer is a leading cause of death worldwide, efforts are being made to elucidate molecular mechanisms that trigger or delay carcinogenesis. Phytochemicals, in particular, have been shown to modulate oncogenic processes through their antioxidant and anti-inflammatory activities and their ability to mimic the chemical structure and activity of hormones. These compounds can act not only by influencing oncogenic proteins, but also by modulating noncoding RNAs such as microRNAs and long noncoding RNAs. Although we are only beginning to understand the complete effects of many natural compounds, such as phytochemicals, researchers are motivated to combine these agents with traditional, chemo-based, or hormone-based therapies to fight against cancer. Since ongoing studies continue to prove effective, herein we exalt the importance of improving dietary choices as a chemo preventive strategy. PMID- 26273210 TI - Border Enforcement and Return Migration by Documented and Undocumented Mexicans. AB - Using data from the Mexican Migration Project we compute probabilities of departure and return for first and later trips to the United States in both documented and undocumented status. We then estimate statistical models to analyze the determinants of departure and return according to legal status. Prior to 1986, Mexico-U.S. migration was characterized by great circularity, but since then circularity has declined markedly for undocumented migrants but increased dramatically for documented migrants. Whereas return migration by undocumented migrants dropped in response to the massive increase in border enforcement, that of documented migrants did not. At present, the Mexico-U.S. migration system has reached a new equilibrium in which undocumented migrants are caged in as long term settlers in the United States while documented migrants increasingly range freely and circulate back and forth across the border within rising frequency. PMID- 26273211 TI - Optimizing the 'demographic dividend' in young developing countries: The role of contractual savings and insurance for financing education. AB - Many developing regions are facing a youth bulge, meaning that young people comprise the highest proportion of the population. These regions are at risk of losing what could be a tremendous opportunity for economic growth and development if they do not capitalize on this young and economically productive population - also referred to as the "demographic dividend," defined as the increase in economic growth that tends to follow increases in the ratio of the working-age population - essentially the labor force - to dependents. Nations undergoing this population transition have the opportunity to capitalize on the demographic dividend if the right social, economic, and human capital policies are in place. In particular, sub-Saharan Africa, the Middle East, and North Africa are at risk of losing the demographic dividend. These regions face high youth unemployment, low primary school completion, and low secondary school enrollment. This results in an undereducated and unskilled segment of the population. The prohibitive costs of education prevent young people from finishing school, thereby entering the labor market unprepared. This article presents a case for youth-focused financial inclusion programs as one of the antidotes to the masses of poor, undereducated, and low-skilled young people swelling the labor markets of poor developing countries. PMID- 26273213 TI - Synthesis, structural studies, and oxidation catalysis of the manganese(II), iron(II), and copper(II) complexes of a 2-pyridylmethyl pendant armed side bridged cyclam. AB - The first 2-pyridylmethyl pendant armed structurally reinforced cyclam ligand has been synthesized and successfully complexed to Mn2+, Fe2+, and Cu2+ cations. X ray crystal structures were obtained for the diprotonated ligand and its Cu2+ complex demonstrating pentadentate binding of the ligand with trans-II configuration of the side-bridged cyclam ring, leaving a potential labile binding site cis to the pyridine donor for interaction of the complex with oxidants and/or substrates. The electronic properties of these complexes were determined by means of solid state magnetic moment, with a low value of MU = 3.10 MUB for the Fe2+ complex suggesting it has a trigonal bipyramidal coordination geometry, matching the crystal structure of the Cu2+ complex, while the MU = 5.52 MUB value for the Mn2+ complex suggests it is high spin octahedral. Cyclic voltammetry in acetonitrile revealed reversible redox processes in all three complexes, suggesting catalytic reactivity involving electron transfer processes are possible for these complexes. Screening for oxidation catalysis using hydrogen peroxide as the terminal oxidant identified the Fe2+ complex as the oxidation catalysts most worthy of continued development. PMID- 26273214 TI - CYP3A5 genotyping for assessing the efficacy of treatment with simvastatin and atorvastatin. AB - In this work, we examined the impact of polymorphism in the cytochrome P450 (CYP) 3A5 gene, CYP3A5*1 (6986A > G, rs 776746), on the reduction in the lipid levels caused by simvastatin and atorvastatin. We studied 350 hyperlipidemic patients who received 10-40 mg of atorvastatin (n = 175) or simvastatin (n = 175) daily. Genotyping for CYP3A5 was done by PCR-RFLP analysis. Differences in the lipid profile before and after treatment were expressed as the % difference. The frequency of CYP3A5polymorphism was 13.4% for heterozygotes and 86.6% for homozygotes. Comparison of the responses to same dose of each drug showed that the highest % difference was associated with total cholesterol (TC) in subjects receiving atorvastatin 40 mg compared with simvastatin 40 mg (p = 0.048). However, comparison of the responses to equivalent doses of atorvastatin vs. simvastatin revealed no difference in the % change in any of the lipid parameters examined. In individuals with the same CYP3A5 genotype, a head to head comparison of the efficacy of the same dose of simvastatin vs. atorvastatin revealed an advantage for atorvastatin. For equivalent doses of atorvastatin vs. simvastatin there was no difference in the % change in any of the lipid parameters examined. Within the same genotype there was a significant difference in the % change related to the drug treatment. PMID- 26273212 TI - Multi-trait multi-environment quantitative trait loci mapping for a sugarcane commercial cross provides insights on the inheritance of important traits. AB - Breeding trials typically consist of phenotypic observations for various traits evaluated in multiple environments. For sugarcane in particular, repeated measures are obtained for plant crop and one or more ratoons, such that joint analysis through mixed models for modeling heterogeneous genetic (co)variances between traits, locations and harvests is appropriate. This modeling approach also enables us to include molecular marker information, aiding in understanding the genetic architecture of quantitative traits. Our work aims at detecting QTL and QTL by environment interactions by fitting mixed models with multiple QTLs, with appropriate modeling of multi-trait multi-environment data for outcrossing species. We evaluated 100 individuals from a biparental cross at two locations and three years for fiber content, sugar content (POL) and tonnes of cane per hectare (TCH). We detected 13 QTLs exhibiting QTL by location, QTL by harvest or the three-way interaction. Overall, 11 of the 13 effects presented some degree of pleiotropy, affecting at least two traits. Furthermore, these QTLs always affected fiber and TCH in the same direction, whereas POL was affected in the opposite way. There was no evidence in favor of the linked QTL over the pleiotropic QTL hypothesis for any detected genome position. These results provide valuable insights into the genetic basis of quantitative variation in sugarcane and the genetic relation between traits. PMID- 26273215 TI - Genetic association of single nucleotide polymorphisms in dystrobrevin binding protein 1 gene with schizophrenia in a Malaysian population. AB - Dystrobrevin binding protein 1 (DTNBP1) gene is pivotal in regulating the glutamatergic system. Genetic variants of the DTNBP1 affect cognition and thus may be particularly relevant to schizophrenia. We therefore evaluated the association of six single nucleotide polymorphisms (SNPs) with schizophrenia in a Malaysian population (171 cases; 171 controls). Associations between these six SNPs and schizophrenia were tested in two stages. Association signals with p < 0.05 and minor allele frequency > 0.05 in stage 1 were followed by genotyping the SNPs in a replication phase (stage 2). Genotyping was performed with sequenced specific primer (PCR-SSP) and restriction fragment length polymorphism (PCR RFLP). In our sample, we found significant associations between rs2619522 (allele p = 0.002, OR = 1.902, 95%CI = 1.266 - 2.859; genotype p = 0.002) and rs2619528 (allele p = 0.008, OR = 1.606, 95%CI = 1.130 - 2.281; genotype p = 6.18 * 10(-5)) and schizophrenia. Given that these two SNPs may be associated with the pathophysiology of schizophrenia, further studies on the other DTNBP1 variants are warranted. PMID- 26273216 TI - DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy. AB - Centronuclear myopathy (CNM) is a rare congenital muscle disease characterized by fibers with prominent centralized nuclei in muscle biopsies. The disease is clinically heterogeneous, ranging from severe neonatal hypotonic phenotypes to adult-onset mild muscle weakness, and can have multiple modes of inheritance in association with various genes, including MTM1, DNM2, BIN1 and RYR1. Here we analyzed 18 sporadic patients with clinical and histological diagnosis of CNM and sequenced the DNM2 gene, which codes for the dynamin 2 protein. We found DNM2 missense mutations in two patients, both in exon 8, one known (p.E368K) and one novel (p.F372C), which is found in a position of presumed pathogenicity and appeared de novo. The patients had similar phenotypes characterized by neonatal signs followed by improvement and late childhood reemergence of slowly progressive generalized muscle weakness, elongated face with ptosis and ophthalmoparesis, and histology showing fibers with radiating sarcoplasmic strands (RSS). These patients were the only ones in the series to present this histological marker, which together with previous reports in the literature suggest that, when RSS are present, direct sequencing of DNM2 mutation hot spot regions should be the first step in the molecular diagnosis of CNM, even in sporadic cases. PMID- 26273217 TI - Human population genetic structure detected by pain-related mu opioid receptor gene polymorphisms. AB - Several single nucleotide polymorphisms (SNPs) in the Mu Opioid Receptor gene (OPRM1) have been identified and associated with a wide variety of clinical phenotypes related both to pain sensitivity and analgesic requirements. The A118G and other potentially functional OPRM1 SNPs show significant differences in their allele distributions among populations. However, they have not been properly addressed in a population genetic analysis. Population stratification could lead to erroneous conclusions when they are not taken into account in association studies. The aim of our study was to analyze OPRM1 SNP variability by comparing population samples of the International Hap Map database and to analyze a new population sample from the city of Corrientes, Argentina. The results confirm that OPRM1 SNP variability differs among human populations and displays a clear ancestry genetic structure, with three population clusters: Africa, Asia, and Europe-America. PMID- 26273218 TI - Cytogenetic studies in six species of Scinax (Anura, Hylidae) clade Scinax ruber from northern and northeastern Brazil. AB - Scinax species are still underrepresented in cytogenetic studies, mainly with respect to populations from northeastern and northern Brazil. In this study, we provide new chromosomal information on Scinax boesemani, S. camposseabrai, S. garbei, S. pachycrus, S. trilineatus and S. x-signatus, all belonging to clade S. ruber. They were collected at two locations in the Caatinga biome (northeastern Brazil) and at one in the Amazon (northern Brazil) biomes. Chromosomes were analyzed by conventional staining, C-banding, Ag-NOR staining, and fluorochrome staining. All species shared a modal diploid value of 2n = 24 and fundamental arm number (FN) of 48. Moreover, both chromosomal size and morphology were similar to other species in this Scinaxclade. C-banding revealed centromeric heterochromatin in all species, along with terminal species-specific C-bands in some species. Active nucleolar organizer regions (Ag-NORs) were identified at 11q in most species, except for S. boesemani and S. garbei (Ag-NORs at interstitial region of 8q). Differing from most anurans, GC-rich regions were not restricted to NORs, but also coincident with some centromeric and terminal C-bands. These data contribute to the cytotaxonomy of Scinax by providing chromosomal markers and demonstrating the occurrence of microstructural rearrangements and inversions on chromosomal evolution of Scinax. PMID- 26273219 TI - The complete mitochondrial genome sequence of the little egret (Egretta garzetta). AB - Many phylogenetic questions in the Ciconiiformes remain unresolved and complete mitogenome data are urgently needed for further molecular investigation. In this work, we determined the complete mitogenome sequence of the little egret (Egretta garzetta). The genome was 17,361 bp in length and the gene organization was typical of other avian mtDNA. In protein-coding genes (PCGs), a C insertion was found in ND3, and COIII and ND4 terminated with incomplete stop codons (T). tRNA Val and tRNA-Ser (AGY) were unable to fold into canonical cloverleaf secondary structures because they had lost the DHU arms. Long repetitive sequences consisting of five types of tandem repeats were found at the 3' end of Domain III in the control region. A phylogenetic analysis of 11 species of Ciconiiformes was done using complete mitogenome data and 12 PCGs. The tree topologies obtained with these two strategies were identical, which strongly confirmed the monophyly of Ardeidae, Threskiorothidae and Ciconiidae. The phylogenetic analysis also revealed that Egretta was more closely related to Ardea than to Nycticorax in the Ardeidae, and Platalea was more closely related to Threskiornis than to Nipponia in the Threskiornithidae. These findings contribute to our understanding of the phylogenetic relationships of Ciconiiformes based on complete mitogenome data. PMID- 26273220 TI - Presence of two mitochondrial genomes in the mytilid Perumytilus purpuratus: Phylogenetic evidence for doubly uniparental inheritance. AB - This study presents evidence, using sequences of ribosomal 16S and COI mtDNA, for the presence of two mitochondrial genomes in Perumytilus purpuratus. This may be considered evidence of doubly uniparental mtDNA inheritance. The presence of the two types of mitochondrial genomes differentiates females from males. The F genome was found in the somatic and gonadal tissues of females and in the somatic tissues of males; the M genome was found in the gonads and mantle of males only. For the mitochondrial 16S region, ten haplotypes were found for the F genome (nucleotide diversity 0.004), and 7 haplotypes for the M genome (nucleotide diversity 0.001), with a distance Dxy of 0.125 and divergence Kxy of 60.33%. For the COI gene 17 haplotypes were found for the F genome (nucleotide diversity 0.009), and 10 haplotypes for the M genome (nucleotide diversity 0.010), with a genetic distance Dxy of 0.184 and divergence Kxy of 99.97%. Our results report the presence of two well-differentiated, sex-specific types of mitochondrial genome (one present in the male gonad, the other in the female gonad), implying the presence of DUI in P. purpuratus. These results indicate that care must be taken in phylogenetic comparisons using mtDNA sequences of P. purpuratus without considering the sex of the individuals. PMID- 26273221 TI - Galactinol synthase transcriptional profile in two genotypes of Coffea canephora with contrasting tolerance to drought. AB - Increased synthesis of galactinol and raffinose family oligosaccharides (RFOs) has been reported in vegetative tissues in response to a range of abiotic stresses. In this work, we evaluated the transcriptional profile of a Coffea canephora galactinol synthase gene (CcGolS1) in two clones that differed in tolerance to water deficit in order to assess the contribution of this gene to drought tolerance. The expression of CcGolS1 in leaves was differentially regulated by water deficit, depending on the intensity of stress and the genotype. In clone 109A (drought-susceptible), the abundance of CcGolS1 transcripts decreased upon exposure to drought, reaching minimum values during recovery from severe water deficit and stress. In contrast, CcGolS1 gene expression in clone 14 (drought-tolerant) was stimulated by water deficit. Changes in galactinol and RFO content did not correlate with variation in the steady-state transcript level. However, the magnitude of increase in RFO accumulation was higher in the tolerant cultivar, mainly under severe water deficit. The finding that the drought-tolerant coffee clone showed enhanced accumulation of CcGolS1 transcripts and RFOs under water deficit suggests the possibility of using this gene to improve drought tolerance in this important crop. PMID- 26273222 TI - Eucalyptus urograndis stem proteome is responsive to short-term cold stress. AB - Eucalyptus urograndis is a hybrid eucalyptus of major economic importance to the Brazilian pulp and paper industry. Although widely used in forest nurseries around the country, little is known about the biochemical changes imposed by environmental stress in this species. In this study, we evaluated the changes in the stem proteome after short-term stimulation by exposure to low temperature. Using two-dimensional gel electrophoresis coupled to high-resolution mass spectrometry-based protein identification, 12 proteins were found to be differentially regulated and successfully identified after stringent database searches against a protein database from a closely related species (Eucalyptus grandis). The identification of these proteins indicated that the E. urograndis stem proteome responded quickly to low temperature, mostly by down-regulating specific proteins involved in energy metabolism, protein synthesis and signaling. The results of this study represent the first step in understanding the molecular and biochemical responses of E. urograndis to thermal stress. PMID- 26273224 TI - Microbial quality of soil from the Pampa biome in response to different grazing pressures. AB - The aim of this study was to evaluate the impact of different grazing pressures on the activity and diversity of soil bacteria. We performed a long-term experiment in Eldorado do Sul, southern Brazil, that assessed three levels of grazing pressure: high pressure (HP), with 4% herbage allowance (HA), moderate pressure (MP), with 12% HA, and low pressure (LP), with 16% HA. Two reference areas were also assessed, one of never-grazed native vegetation (NG) and another of regenerated vegetation after two years of grazing (RG). Soil samples were evaluated for microbial biomass and enzymatic (beta-glucosidase, arylsulfatase and urease) activities. The structure of the bacterial community and the population of diazotrophic bacteria were evaluated by RFLP of the 16S rRNA and nifH genes, respectively. The diversity of diazotrophic bacteria was assessed by partial sequencing of the 16S rDNA gene. The presence of grazing animals increased soil microbial biomass in MP and HP. The structures of the bacterial community and the populations of diazotrophic bacteria were altered by the different grazing managements, with a greater diversity of diazotrophic bacteria in the LP treatment. Based on the characteristics evaluated, the MP treatment was the most appropriate for animal production and conservation of the Pampa biome. PMID- 26273223 TI - Comparative karyotype analysis of populations in the Alstroemeria presliana Herbert (Alstroemeriaceae) complex in Chile. AB - Alstroemeria L., one of the most diverse genera of the Chilean flora and of high floricultural value, is represented by 35 species, most of them distributed between 28-38 degrees S in the Mediterranean zone of Central Chile. There are 24 complex-forming taxa, of which 18 have conservation problems (8 are considered "endangered" and 10 as "vulnerable"). One of these complexes is Alstroemeria presliana Herb. with two subspecies: subsp. presliana and subsp. australis Bayer. Alstroemeria presliana grows in Chile and Argentina: subsp. presliana is distributed from Reserva Nacional Siete Tazas (35 degrees 27' S, Region of Maule) to Antuco, (37 degrees 25' S, Region of Bio-Bio), and is also found in Neuquen, Argentina; subsp. australis is endemic to the Cordillera of Nahuelbuta. A comparative karyotype study was carried out among six populations of A. presliana subsp. presliana and five populations of A. presliana subsp. australis. The eleven populations presented an asymmetric karyotype, with 2n = 2* = 16 chromosomes but with different karyotype formulae. A. presliana subsp. presliana shows the haploid formula 2m + 2m-sat + 1sm-sat + 1st-sat + 1t + 1 t-sat, and A. preslianasubsp. australis presents a formula 1m + 2m-sat + 1sm + 2t + 2t-sat chromosomes. The architecture of the karyotype between the subspecies is very different. The scatter plot among CVCL vs. MCA shows different groupings between populations of the two subspecies. According to the results obtained it is possible to consider raising Alstroemeria presliana subsp. australis at species level. PMID- 26273225 TI - X1X1X2X2/X1X2Y sex chromosome systems in the Neotropical Gymnotiformes electric fish of the genus Brachyhypopomus. AB - Several types of sex chromosome systems have been recorded among Gymnotiformes, including male and female heterogamety, simple and multiple sex chromosomes, and different mechanisms of origin and evolution. The X1X1X2X2/X1X2Y systems identified in three species of this order are considered homoplasic for the group. In the genus Brachyhypopomus, only B. gauderio presented this type of system. Herein we describe the karyotypes of Brachyhypopomus pinnicaudatus and B. n. sp. FLAV, which have an X1X1X2X2/X1X2Y sex chromosome system that evolved via fusion between an autosome and the Y chromosome. The morphology of the chromosomes and the meiotic pairing suggest that the sex chromosomes of B. gauderio and B. pinnicaudatus have a common origin, whereas in B . n. sp. FLAV the sex chromosome system evolved independently. However, we cannot discard the possibility of common origin followed by distinct processes of differentiation. The identification of two new karyotypes with an X1X1X2X2/X1X2Y sex chromosome system in Gymnotiformes makes it the most common among the karyotyped species of the group. Comparisons of these karyotypes and the evolutionary history of the taxa indicate independent origins for their sex chromosomes systems. The recurrent emergence of the X1X1X2X2/X1X2Y system may represent sex chromosomes turnover events in Gymnotiformes. PMID- 26273227 TI - Exposure to an extremely low-frequency electromagnetic field only slightly modifies the proteome of Chromobacterium violaceumATCC 12472. AB - Several studies of the physiological responses of different organisms exposed to extremely low-frequency electromagnetic fields (ELF-EMF) have been described. In this work, we report the minimal effects of in situ exposure to ELF-EMF on the global protein expression of Chromobacterium violaceum using a gel-based proteomic approach. The protein expression profile was only slightly altered, with five differentially expressed proteins detected in the exposed cultures; two of these proteins (DNA-binding stress protein, Dps, and alcohol dehydrogenase) were identified by MS/MS. The enhanced expression of Dps possibly helped to prevent physical damage to DNA. Although small, the changes in protein expression observed here were probably beneficial in helping the bacteria to adapt to the stress generated by the electromagnetic field. PMID- 26273228 TI - Social work and gender: An argument for practical accounts. AB - This article contributes to the debate on gender and social work by examining dominant approaches within the field. Anti-discriminatory, woman-centered and intersectional accounts are critiqued for reliance upon both reification and isolation of gender. Via examination of poststructural, queer and trans theories within social work, the author then presents accounts based upon structural/materialist, ethnomethodological and discursive theories, in order to open up debates about conceptualization of gender. These are used to suggest that social work should adopt a focus on gender as a practical accomplishment that occurs within various settings or contexts. PMID- 26273226 TI - The ability of mouse nuclear transfer embryonic stem cells to differentiate into primordial germ cells. AB - Nuclear transfer embryonic stem cells (ntESCs) show stem cell characteristics such as pluripotency but cause no immunological disorders. Although ntESCs are able to differentiate into somatic cells, the ability of ntESCs to differentiate into primordial germ cells (PGCs) has not been examined. In this work, we examined the capacity of mouse ntESCs to differentiate into PGCs in vitro. ntESCs aggregated to form embryoid bodies (EB) in EB culture medium supplemented with bone morphogenetic protein 4(BMP4) as the differentiation factor. The expression level of specific PGC genes was compared at days 4 and 8 using real time PCR. Flow cytometry and immunocytochemical staining were used to detect Mvh as a specific PGC marker. ntESCs expressed particular genes related to different stages of PGC development. Flow cytometry and immunocytochemical staining confirmed the presence of Mvh protein in a small number of cells. There were significant differences between cells that differentiated into PGCs in the group treated with Bmp4 compared to non-treated cells. These findings indicate that ntESCs can differentiate into putative PGCs. Improvement of ntESC differentiation into PGCs may be a reliable means of producing mature germ cells. PMID- 26273229 TI - Effect of home-based light treatment on persons with dementia and their caregivers. AB - Sleep disorders are problematic for persons with dementia and their family caregivers. This randomized controlled trial with crossover evaluated the effects of an innovative blue-white light therapy on 17 pairs of home-dwelling persons with dementia and their caregivers. Subjects with dementia received blue-white light and control ('red-yellow' light) for six weeks separated by a four-week washout. Neither actigraphic nor most self-reported sleep measures significantly differed for subjects with dementia. For caregivers, both sleep and role strain improved. No evidence of retinal light toxicity was observed. Six weeks of modest doses of blue-white light appear to improve sleep in caregivers but not in persons with dementia. Greater or prolonged circadian stimulation may be needed to determine if light is an effective treatment for persons with dementia. PMID- 26273230 TI - ACUTE PELVIC PAIN IN THE ADOLESCENT: A CASE REPORT. AB - Diagnosis and treatment of acute pelvic pain in the adolescent female requires differentiating among a broad differential diagnosis that includes potentially serious illness across several organ systems. The case presented provides an illustration of the assessment and management of acute pelvic pain, and key teaching points about important potential causes. PMID- 26273231 TI - Pathways among Caregiver Education, Household Resources, and Infant Growth in 39 Low- and Middle-Income Countries. AB - Caregiver education is known to relate to the growth of children, but possible mediation mechanisms of this association are poorly characterized and generally lack empirical support. We test whether instructional capital (caregiver education) leads to improved infant growth through availability of physical capital (household resources) across a wide swath of low- and middle-income countries (LMIC). Using the Multiple Indicator Cluster Survey (MICS3), we explore relations among caregiver education, household resources, and infant (M age = .99 years) growth in 117,881 families living in 39 LMIC. Overall, household resources mediated 76% of the small association between caregiver education and infant growth. When disaggregated by countries characterized by low, medium, and high levels of human development (as indexed by average life expectancy, education, and gross domestic product), household resources mediated 48% to 78% of the association between caregiver education and infant growth. Caregiver education had effects on infant growth through household resources in countries characterized by low, medium, and high levels of human development; for girls and boys; and controlling for indexes of infant feeding and health. PMID- 26273233 TI - The Cultural Ecogram: A Tool for Enhancing Culturally Anchored Shared Understanding in the Treatment of Ethnic Minority Families. AB - Ethnic and racial disparities in mental health care continue to exist, highlighting the increasing concern within the realm of clinical practice as to how clinicians are to effectively integrate the central role of culture and context into the treatment delivery process for culturally diverse children and families. The current paper presents the Cultural Ecogram, - a clinical engagement tool designed to facilitate the development of a culturally anchored shared understanding - as one method that may facilitate clinician-client shared understanding on the client's cultural, ethnic and racial context central to the effective implementation of treatments with ethnic minority children and families. PMID- 26273232 TI - The Infant Orienting With Attention task: Assessing the neural basis of spatial attention in infancy. AB - Infant visual attention develops rapidly over the first year of life, significantly altering the way infants respond to peripheral visual events. Here we present data from 5-, 7- and 10-month-old infants using the Infant Orienting With Attention (IOWA) task, designed to capture developmental changes in visual spatial attention and saccade planning. Results indicate rapid development of spatial attention and visual response competition between 5 and 10 months. We use a dynamic neural field (DNF) model to link behavioral findings to neural population activity, providing a possible mechanistic explanation for observed developmental changes. Together, the behavioral and model simulation results provide new insights into the specific mechanisms that underlie spatial cueing effects, visual competition, and visual interference in infancy. PMID- 26273234 TI - Thromboelastography: A Practice Summary for Nurse Practitioners Treating Hemorrhage. AB - Nurse practitioners may manage patients with coagulopathic bleeding which can lead to life-threatening hemorrhage. Routine plasma-based tests such as prothrombin time and activated partial thromboplastin time are inadequate in diagnosing hemorrhagic coagulopathy. Indiscriminate administration of fresh frozen plasma, platelets or cryoprecipitate for coagulopathic states can be extremely dangerous. The qualitative analysis that thromboelastography provides can facilitate the administration of the right blood product, at the right time, thereby permitting the application of goal-directed therapy for coagulopathic intervention application and patient survival. PMID- 26273235 TI - The Use of an Open Field Model to Assess Sound-Induced Fear and Anxiety Associated Behaviors in Labrador Retrievers. AB - Previous studies have shown that the playing of thunderstorm recordings during an open-field task elicits fearful or anxious responses in adult beagles. The goal of our study was to apply this open field test to assess sound-induced behaviors in Labrador retrievers drawn from a pool of candidate improvised explosive devices (IED)-detection dogs. Being robust to fear-inducing sounds and recovering quickly is a critical requirement of these military working dogs. This study presented male and female dogs, with 3 minutes of either ambient noise (Days 1, 3 and 5), recorded thunderstorm (Day 2), or gunfire (Day 4) sounds in an open field arena. Behavioral and physiological responses were assessed and compared to control (ambient noise) periods. An observer blinded to sound treatment analyzed video records of the 9-minute daily test sessions. Additional assessments included measurement of distance traveled (activity), heart rate, body temperature, and salivary cortisol concentrations. Overall, there was a decline in distance traveled and heart rate within each day and over the five-day test period, suggesting that dogs habituated to the open field arena. Behavioral postures and expressions were assessed using a standardized rubric to score behaviors linked to canine fear and anxiety. These fear/anxiety scores were used to evaluate changes in behaviors following exposure to a sound stressor. Compared to control periods, there was an overall increase in fear/anxiety scores during thunderstorm and gunfire sound stimuli treatment periods. Fear/anxiety scores were correlated with distance traveled, and heart rate. Fear/anxiety scores in response to thunderstorm and gunfire were correlated. Dogs showed higher fear/anxiety scores during periods after the sound stimuli compared to control periods. In general, candidate IED-detection Labrador retrievers responded to sound stimuli and recovered quickly, although dogs stratified in their response to sound stimuli. Some dogs were robust to fear/anxiety responses. The results suggest that the open field sound test may be a useful method to evaluate the suitability of dogs for IED-detection training. PMID- 26273236 TI - Prolonged antibiotic use induces intestinal injury in mice that is repaired after removing antibiotic pressure: implications for empiric antibiotic therapy. AB - Metabolic profiling of urine and fecal extracts, histological investigation of intestinal ilea, and fecal metagenomics analyses were used to investigate effects of prolonged antibiotic use in mice. The study provides insight into the effects of extended empiric antibiotic therapy in humans. Mice were administered a broad spectrum antibiotic for four consecutive days followed by oral gavage with Clostridium butyricum, an opportunistic gram-positive pathogenic bacteria commonly isolated in fecal and blood cultures of necrotizing enterocolitis patients. Metagenomics data indicated loss of bacterial diversity after 4 days on antibiotics that was restored after removing antibiotic pressure. Histological analyses indicated damage to ileal villi after antibiotic treatment that underwent repair after lifting antibiotic pressure. Metabolic profiling confirmed intestinal injury in antibiotic-treated mice indicated by increased urinary trans 4-hydroxy-l-proline, a breakdown product of collagen present in connective tissue of ileal villi that may serve as a biomarker for antibiotic-induced injury in at risk populations. PMID- 26273237 TI - Untargeted metabolomics studies employing NMR and LC-MS reveal metabolic coupling between Nanoarcheum equitans and its archaeal host Ignicoccus hospitalis. AB - Interspecies interactions are the basis of microbial community formation and infectious diseases. Systems biology enables the construction of complex models describing such interactions, leading to a better understanding of disease states and communities. However, before interactions between complex organisms can be understood, metabolic and energetic implications of simpler real-world host microbe systems must be worked out. To this effect, untargeted metabolomics experiments were conducted and integrated with proteomics data to characterize key molecular-level interactions between two hyperthermophilic microbial species, both of which have reduced genomes. Metabolic changes and transfer of metabolites between the archaea Ignicoccus hospitalis and Nanoarcheum equitans were investigated using integrated LC-MS and NMR metabolomics. The study of such a system is challenging, as no genetic tools are available, growth in the laboratory is challenging, and mechanisms by which they interact are unknown. Together with information about relative enzyme levels obtained from shotgun proteomics, the metabolomics data provided useful insights into metabolic pathways and cellular networks of I. hospitalis that are impacted by the presence of N. equitans, including arginine, isoleucine, and CTP biosynthesis. On the organismal level, the data indicate that N. equitans exploits metabolites generated by I. hospitalis to satisfy its own metabolic needs. This finding is based on N. equitans's consumption of a significant fraction of the metabolite pool in I. hospitalis that cannot solely be attributed to increased biomass production for N. equitans. Combining LC-MS and NMR metabolomics datasets improved coverage of the metabolome and enhanced the identification and quantitation of cellular metabolites. PMID- 26273239 TI - Assortment of carbon sources in medium for Yarrowia lipolytica lipase production: A statistical approach. AB - Glycerol is considered an important renewable feedstock as well as an undesirable side-product of biodiesel production. The aim of this study was to determine whether supplementing a culture medium with a combination of three different carbon sources (olive oil, glucose and glycerol) would optimize lipase production by the yeast Yarrowia lipolytica. The optimization experiments were conducted with a statistical approach using the mixture design. Analysis of the response surface revealed that it would be possible to compose a medium in which both an an extracellular lipase activity of 0.1 U/mL and up to 37.5 g/L of pure glycerol could be obtained. An YPO-Gl30 medium consisting of 30 g/L glycerol and 19.2 mL/L olive oil was selected for further investigation. Although a high biomass yield was found in all cultures, the glycerol content of the YPO-Gl30 medium slightly influenced yeast growth, but it did not prolong the duration of the lag phase. The hydrolytic activity of the extracellular lipases produced in YPO-Gl30 medium was satisfactory. PMID- 26273238 TI - Environmental scanning electron microscopy analysis of Proteus mirabilis biofilms grown on chitin and stainless steel. AB - Proteus mirabilis is a human pathogen able to form biofilms on the surface of urinary catheters. Little is known about P. mirabilis biofilms on natural or industrial surfaces and the potential consequences for these settings. The main aim of this work was to assess and compare the adhesion and biofilm formation of P. mirabilis strains from different origins on chitin and stainless steel surfaces within 4 to 96 h. Using environmental scanning electron microscopy, the biofilms of a clinical strain grown on chitin at 4 h showed greater adhesion, aggregation, thickness, and extracellular matrix production than those grown on stainless steel, whereas biofilms of an environmental strain had less aggregation on both surfaces. Biofilms of both P. mirabilis strains developed different structures on chitin, such as pillars, mushrooms, channels, and crystalline-like precipitates between 24 and 96 h, in contrast with flat-layer biofilms produced on stainless steel. Significant differences (p < 0.05) were found in the frequency of pillars and channels. Images of transmission electron microscopy demonstrated abundant fimbriae in 100 % of cells from both strains, which could be related to surface adherence and biofilm formation. This represents the first study of P. mirabilis showing adhesion, biofilm formation, and development of different structures on surfaces found outside the human host. PMID- 26273240 TI - Antimicrobial activity of low-pressure plasma treatment against selected foodborne bacteria and meat microbiota. AB - The effects of helium and argon plasma treatments on inactivation of both pure bacterial cultures inoculated onto the surface of agarized media and the surface microbiota of meat were investigated. Cold plasmas were generated by high voltage discharge at low pressure (20 kPa) for 2, 5, and 10 min. The number of viable microorganisms was determined using a plate count method. Morphological changes were observed using scanning electron microscopy (SEM). Microbial log reduction depended on time of exposure and type of gas used. After a 10-min treatment with helium plasma, the total number of microorganisms, yeasts and molds, and psychrotrophic microorganisms was reduced in the range of 1.14-1.48 log cycles for pork and 0.98-2.09 log cycles for beef. A significant reduction of 2.00 log for Bacillus subtilis and Yersinia enterocolitica was achieved within 2 min of helium plasma treatment. Similar results were obtained for Staphylococcus aureus, Escherichia coli and Pseudomonas fluorescens after 5 min and 10 min of exposure. SEM revealed disruption and lysis of E. coli cells treated with helium plasma for 10 min, suggesting a bactericidal effect. PMID- 26273241 TI - Soil chemical properties affect the reaction of forest soil bacteria to drought and rewetting stress. AB - Reaction of soil bacteria to drought and rewetting stress may depend on soil chemical properties. The objectives of this study were to test the reaction of different bacterial phyla to drought and rewetting stress and to assess the influence of different soil chemical properties on the reaction of soil bacteria to this kind of stress. The soil samples were taken at ten forest sites and measured for pH and the contents of organic C (Corg) and total N (Nt), Zn, Cu, and Pb. The samples were kept without water addition at 20 - 30 degrees C for 8 weeks and subsequently rewetted to achieve moisture equal to 50 - 60 % of their maximum water-holding capacity. Prior to the drought period and 24 h after the rewetting, the structure of soil bacterial communities was determined using pyrosequencing of 16S rRNA genes. The drought and rewetting stress altered bacterial community structure. Gram-positive bacterial phyla, Actinobacteria and Firmicutes, increased in relative proportion after the stress, whereas the Gram negative bacteria in most cases decreased. The largest decrease in relative abundance was for Gammaproteobacteria and Bacteroidetes. For several phyla the reaction to drought and rewetting stress depended on the chemical properties of soils. Soil pH was the most important soil property influencing the reaction of a number of soil bacterial groups (including all classes of Proteobacteria, Bacteroidetes, Acidobacteria, and others) to drought and rewetting stress. For several bacterial phyla the reaction to the stress depended also on the contents of Nt and Corg in soil. The effect of heavy metal pollution was also noticeable, although weaker compared to other chemical soil properties. We conclude that soil chemical properties should be considered when assessing the effect of stressing factors on soil bacterial communities. PMID- 26273242 TI - Injectable Hydrogels with In Situ Double Network Formation Enhance Retention of Transplanted Stem Cells. PMID- 26273243 TI - Neuropsychological Characteristics and Their Association with Higher-Level Functional Capacity in Parkinson's Disease. AB - BACKGROUND/AIMS: Little is known about the relationship between cognitive functions and higher-level functional capacity (e.g. intellectual activity, social role, and social participation) in Parkinson's disease (PD). The purpose of this study was to clarify neuropsychological characteristics and their association with higher-level functional capacity in PD patients. METHODS: Participants were 31 PD patients and 23 demographically matched healthy controls. Neuropsychological tests were conducted. One year later, a questionnaire survey evaluated higher-level functional capacity in daily living. RESULTS: The PD group scored significantly lower than the control group in all cognitive domains, particularly executive function and processing. Executive function, processing speed, language, and memory were significantly correlated with higher-level functional capacity in PD patients. Stepwise regression showed that only executive function (Trail Making Test-B), together with disease severity (HY stage), predicted the higher-level functional capacity. CONCLUSION: Our findings provide evidence of a relationship between executive function and higher-level functional capacity in patients with PD. PMID- 26273244 TI - Daytime Sleepiness and Sleep Inadequacy as Risk Factors for Dementia. AB - BACKGROUND/AIMS: To examine the association between self-reported sleep problems and incidence of dementia in community-dwelling elderly people. METHODS: 1,041 nondemented participants over 65 years old were examined longitudinally. Sleep problems were estimated using the RAND Medical Outcomes Study Sleep Scale examining sleep disturbance, snoring, sleep short of breath or with a headache, sleep adequacy, and sleep somnolence. Cox regression analysis was used to examine the association between sleep problems and risk for incident dementia. Age, gender, education, ethnicity, APOE-epsilon4, stroke, heart disease, hypertension, diabetes, and depression were included as covariates. RESULTS: Over 3 years of follow-up, 966 (92.8%) participants remained nondemented, while 78 (7.2%) developed dementia. In unadjusted models, sleep inadequacy ('Get the amount of sleep you need') at the initial visit was associated with increased risk of incident dementia (HR = 1.20; 95% CI 1.02-1.42; p = 0.027). Adjusting for all the covariates, increased risk of incident dementia was still associated with sleep inadequacy (HR = 1.20; 95% CI 1.01-1.42; p = 0.040), as well as with increased daytime sleepiness ('Have trouble staying awake during the day') (HR = 1.24; 95% CI 1.00-1.54; p = 0.047). CONCLUSION: Our results suggest that sleep inadequacy and increased daytime sleepiness are risk factors for dementia in older adults, independent of demographic and clinical factors. PMID- 26273245 TI - Psychrotrophic bacteria in milk: How much do we really know? AB - The occurrence of psychrotrophic bacteria in raw milk is studied worldwide due to the difficulties associated with controlling their growth during cold storage and the consequent negative effects upon fluid milk or dairy products. Among the psychrotrophic bacteria, the genus Pseudomonas (represented primarily by P. fluorescens) has been highlighted as the cause of numerous defects in dairy products. In light of its perceived predominance, this species has frequently been chosen as a model organism to assess the effects of psychrotrophic bacteria on milk or to evaluate the efficacy of control measures. However, recent findings derived from the application of molecular biological techniques have exposed a number of deficiencies in our knowledge of the biology of milk-associated psychrotrophs. Furthermore, it has been revealed that microbe to microbe communication plays a significant role in determining both the identities and the extent to which different groups of microbes develop during cold storage. The application of molecular identification methods has exposed errors in the classification of members of the genus Pseudomonas isolated from cold stored milk and has stimulated a reevaluation of the presumed status of P. fluorescens as the predominant milk-associated psychrotrophic species. This article presents a succinct review of data from studies on psychrotrophic bacteria in milk, some of which contest established theories in relation to the microbiology of cold stored raw milk, and poses the question: how much do we really know? PMID- 26273246 TI - Fermentative hydrogen production from agroindustrial lignocellulosic substrates. AB - To achieve economically competitive biological hydrogen production, it is crucial to consider inexpensive materials such as lignocellulosic substrate residues derived from agroindustrial activities. It is possible to use (1) lignocellulosic materials without any type of pretreatment, (2) lignocellulosic materials after a pretreatment step, and (3) lignocellulosic materials hydrolysates originating from a pretreatment step followed by enzymatic hydrolysis. According to the current literature data on fermentative H2 production presented in this review, thermophilic conditions produce H2 in yields approximately 75% higher than those obtained in mesophilic conditions using untreated lignocellulosic substrates. The average H2 production from pretreated material is 3.17 +/- 1.79 mmol of H2/g of substrate, which is approximately 50% higher compared with the average yield achieved using untreated materials (2.17 +/- 1.84 mmol of H2/g of substrate). Biological pretreatment affords the highest average yield 4.54 +/- 1.78 mmol of H2/g of substrate compared with the acid and basic pretreatment - average yields of 2.94 +/- 1.85 and 2.41 +/- 1.52 mmol of H2/g of substrate, respectively. The average H2 yield from hydrolysates, obtained from a pretreatment step and enzymatic hydrolysis (3.78 +/- 1.92 mmol of H2/g), was lower compared with the yield of substrates pretreated by biological methods only, demonstrating that it is important to avoid the formation of inhibitors generated by chemical pretreatments. Based on this review, exploring other microorganisms and optimizing the pretreatment and hydrolysis conditions can make the use of lignocellulosic substrates a sustainable way to produce H2. PMID- 26273247 TI - A biotechnology perspective of fungal proteases. AB - Proteases hydrolyze the peptide bonds of proteins into peptides and amino acids, being found in all living organisms, and are essential for cell growth and differentiation. Proteolytic enzymes have potential application in a wide number of industrial processes such as food, laundry detergent and pharmaceutical. Proteases from microbial sources have dominated applications in industrial sectors. Fungal proteases are used for hydrolyzing protein and other components of soy beans and wheat in soy sauce production. Proteases can be produced in large quantities in a short time by established methods of fermentation. The parameters such as variation in C/N ratio, presence of some sugars, besides several other physical factors are important in the development of fermentation process. Proteases of fungal origin can be produced cost effectively, have an advantage faster production, the ease with which the enzymes can be modified and mycelium can be easily removed by filtration. The production of proteases has been carried out using submerged fermentation, but conditions in solid state fermentation lead to several potential advantages for the production of fungal enzymes. This review focuses on the production of fungal proteases, their distribution, structural-functional aspects, physical and chemical parameters, and the use of these enzymes in industrial applications. PMID- 26273248 TI - Halotolerant bacteria in the Sao Paulo Zoo composting process and their hydrolases and bioproducts. AB - Halophilic microorganisms are able to grow in the presence of salt and are also excellent source of enzymes and biotechnological products, such as exopolysaccharides (EPSs) and polyhydroxyalkanoates (PHAs). Salt-tolerant bacteria were screened in the Organic Composting Production Unit (OCPU) of Sao Paulo Zoological Park Foundation, which processes 4 ton/day of organic residues including plant matter from the Atlantic Rain Forest, animal manure and carcasses and mud from water treatment. Among the screened microorganisms, eight halotolerant bacteria grew at NaCl concentrations up to 4 M. These cultures were classified based on phylogenetic characteristics and comparative partial 16S rRNA gene sequence analysis as belonging to the genera Staphylococcus, Bacillus and Brevibacterium. The results of this study describe the ability of these halotolerant bacteria to produce some classes of hydrolases, namely, lipases, proteases, amylases and cellulases, and biopolymers. The strain characterized as of Brevibacterium avium presented cellulase and amylase activities up to 4 M NaCl and also produced EPSs and PHAs. These results indicate the biotechnological potential of certain microorganisms recovered from the composting process, including halotolerant species, which have the ability to produce enzymes and biopolymers, offering new perspectives for environmental and industrial applications. PMID- 26273249 TI - A new culture medium for recovering the agents of Cryptococcosis from environmental sources. AB - The isolation of Cryptococcosis agents from environmental samples may be difficult due to the presence of groups of fast-growing fungi. We propose a new culture medium based on a modification of Dichloran Rose-Bengal Chloramphenicol Medium (DRBCm) to detect colonies of Cryptococcus neoformans. Our results indicate that DRBCm is superior to the classical Bird Seed Agar in its ability to detect colonies of C. neoformans. PMID- 26273250 TI - Antifungal and proteolytic activities of endophytic fungi isolated from Piper hispidum Sw. AB - Endophytes are being considered for use in biological control, and the enzymes they secrete might facilitate their initial colonization of internal plant tissues and direct interactions with microbial pathogens. Microbial proteases are also biotechnologically important products employed in bioremediation processes, cosmetics, and the pharmaceutical, photographic and food industries. In the present study, we evaluated antagonism and competitive interactions between 98 fungal endophytes and Alternaria alternata, Colletotrichum sp., Phyllosticta citricarpa and Moniliophthora perniciosa. We also examined the proteolytic activities of endophytes grown in liquid medium and conducted cup plate assays. The results showed that certain strains in the assemblage of P. hispidum endophytes are important sources of antifungal properties, primarily Lasiodiplodia theobromae JF766989, which reduced phytopathogen growth by approximately 54 to 65%. We detected 28 endophytes producing enzymatic halos of up to 16.40 mm in diameter. The results obtained in the present study highlight the proteolytic activity of the endophytes Phoma herbarum JF766995 and Schizophyllum commune JF766994, which presented the highest enzymatic halo diameters under at least one culture condition tested. The increased activities of certain isolates in the presence of rice or soy flour as a substrate (with halos up to 17.67 mm in diameter) suggests that these endophytes have the potential to produce enzymes using agricultural wastes. PMID- 26273251 TI - Initial pH of medium affects organic acids production but do not affect phosphate solubilization. AB - The pH of the culture medium directly influences the growth of microorganisms and the chemical processes that they perform. The aim of this study was to assess the influence of the initial pH of the culture medium on the production of 11 low molecular-weight organic acids and on the solubilization of calcium phosphate by bacteria in growth medium (NBRIP). The following strains isolated from cowpea nodules were studied: UFLA03-08 (Rhizobium tropici), UFLA03-09 (Acinetobacter sp.), UFLA03-10 (Paenibacillus kribbensis), UFLA03-106 (Paenibacillus kribbensis) and UFLA03-116 (Paenibacillus sp.). The strains UFLA03-08, UFLA03-09, UFLA03-10 and UFLA03-106 solubilized Ca3(PO4)2 in liquid medium regardless of the initial pH, although without a significant difference between the treatments. The production of organic acids by these strains was assessed for all of the initial pH values investigated, and differences between the treatments were observed. Strains UFLA03-09 and UFLA03-10 produced the same acids at different initial pH values in the culture medium. There was no correlation between phosphorus solubilized from Ca3(PO4)2 in NBRIP liquid medium and the concentration of total organic acids at the different initial pH values. Therefore, the initial pH of the culture medium influences the production of organic acids by the strains UFLA03-08, UFLA03-09, UFLA03-10 and UFLA03-106 but it does not affect calcium phosphate solubilization. PMID- 26273252 TI - Biodegradation of crude oil by individual bacterial strains and a mixed bacterial consortium. AB - Three bacterial isolates identified as Alcanivorax borkumensis SK2, Rhodococcus erythropolis HS4 and Pseudomonas stutzeri SDM, based on 16S rRNA gene sequences, were isolated from crude oil enrichments of natural seawater. Single strains and four bacterial consortia designed by mixing the single bacterial cultures respectively in the following ratios: (Alcanivorax: Pseudomonas, 1:1), (Alcanivorax: Rhodococcus, 1:1), (Pseudomonas: Rhodococcus, 1:1), and (Alcanivorax: Pseudomonas: Rhodococcus, 1:1:1), were analyzed in order to evaluate their oil degrading capability. All experiments were carried out in microcosms systems containing seawater (with and without addition of inorganic nutrients) and crude oil (unique carbon source). Measures of total and live bacterial abundance, Card-FISH and quali-, quantitative analysis of hydrocarbons (GC-FID) were carried out in order to elucidate the co-operative action of mixed microbial populations in the process of biodegradation of crude oil. All data obtained confirmed the fundamental role of bacteria belonging to Alcanivorax genus in the degradation of linear hydrocarbons in oil polluted environments. PMID- 26273253 TI - Hypocholesterolemic effects of Kluyveromyces marxianus M3 isolated from Tibetan mushrooms on diet-induced hypercholesterolemia in rat. AB - To investigate the effects of Kluyveromyces marxianus M3 isolated from Tibetan mushrooms on diet-induced hypercholesterolemia in rats, female Wistar rats were fed a high-cholesterol diet (HCD) for 28 d to generate hyperlipidemic models. Hyperlipidemic rats were assigned to four groups, which were individually treated with three different dosages of K. marxianus M3+HCD or physiological saline+HCD via oral gavage for 28 d. The total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels in the serum and liver of the rats were measured using commercially available enzyme kits. In addition, the liver morphology was also examined using hematoxylin and eosin staining and optical microscopy. According to our results, the serum and liver TC, TG, LDL-C levels and atherogenic index (AI) were significantly decreased in rats orally administered K. marxianus M3 (p <0.01), and the HDL-C levels and anti atherogenic index (AAI) were significantly increased (p <0.01) compared to the control group. Moreover, K. marxianus M3 treatment also reduced the build-up of lipid droplets in the liver and exhibited normal hepatocytes, suggesting a protective effect of K. marxianus M3 in hyperlipidemic rats. PMID- 26273254 TI - Biodegradation of kerosene: Study of growth optimization and metabolic fate of P. janthinellum SDX7. AB - Penicillum janthinellum SDX7 was isolated from aged petroleum hydrocarbon affected soil at the site of Anand, Gujarat, India, and was tested for different pH, temperature, agitation and concentrations for optimal growth of the isolate that was capable of degrading upto 95%, 63% and 58% of 1%, 3% and 5% kerosene, respectively, after a period of 16 days, at optimal growth conditions of pH 6.0, 30 degrees C and 180 rpm agitation. The GC/MS chromatograms revealed that then alkane fractions are easily degraded; however, the rate might be lower for branched alkanes, n-alkylaromatics, cyclic alkanes and polynuclear aromatics. The test doses caused a concentration-dependent depletion of carbohydrates of P. janthinellum SDX7 by 3% to 80%, proteins by 4% to 81% and amino acids by 8% to 95% upto 16 days of treatment. The optimal concentration of 3% kerosene resulted in the least reduction of the metabolites of P. janthinellum such as carbohydrates, proteins and amino acids with optimal growth compared to 5% and 1% (v/v) kerosene doses on the 12(th) and 16(th) day of exposure. Phenols were found to be mounted by 43% to 66% at lower and higher concentrations during the experimental period. Fungal isolate P. janthinellum SDX7 was also tested for growth on various xenobiotic compounds. PMID- 26273255 TI - Industrial wastewater as raw material for exopolysaccharide production by Rhizobium leguminosarum. AB - The objective of this study was to evaluate the exopolysaccharide (EPS) production by Rhizobium leguminosarum cultivated in wastewater generated by oil companies (WWOC1 and WWOC2) and fish processing industry (WWFP). The results obtained in Erlenmeyer flasks indicated that the rhizobial strain grew well in industrial wastewater. Generally, wastewater composition affected the growth and the EPS production. WWFP allowed good bacterial growth similar to that obtained with the standard medium (YMB). During growth, various quantities of EPS were produced and yields varied depending on the media. Growing in YMB, EPS production did not exceed 9.7 g/L obtained after 72 h of growth. In wastewater, the maximum EPS value reached 11.1 g/L obtained with the fish processing wastewater, after 72 h of growth. The use of a mixture of the oil company wastewater (WWOC2) and the fish processing wastewater (WWFP) as culture medium affected not only the rhizobial strain growth, but also EPS production. The highest EPS (42.4 g/L, after 96 h of culture) was obtained using a ratio of WWFP and WWOC2 of 50:50 (v:v). Therefore, this work shows the ability of Rhizobium leguminosarum, growing in industrial wastewater as new economic medium, to produce EPS. This biopolymer could be applied in enormous biotechnological areas. PMID- 26273256 TI - Efficacy of fungal decolorization of a mixture of dyes belonging to different classes. AB - Dyes are the most difficult constituents to remove by conventional biological wastewater treatment. Colored wastewater is mainly eliminated by physical and chemical procedures, which are very expensive and have drawbacks. Therefore, the advantage of using biological processes, such as the biotransformation of dyes, is that they may lead to complete mineralization or formation of less toxic products. To prove the possibility of using fungal processes for decolorization and other applications, the analysis of the toxicity of the processes' products is required. The decolorization of the mixture of two dyes from different classes - triphenylmethane brilliant green and azo Evans blue (GB - total concentration 0.08 g/L, proportion 1:1 w/w) - by Pleurotus ostreatus (BWPH and MB), Gloeophyllum odoratum (DCa), RWP17 (Polyporus picipes) and Fusarium oxysporum (G1) was studied. Zootoxicity (Daphnia magna) and phytotoxicity (Lemna minor) changes were estimated at the end of the experiment. The mixture of dyes was significantly removed by all the strains that were tested with 96 h of experimental time. However, differences among strains from the same species (P. ostreatus) were noted. Shaking improved the efficacy and rate of the dye removal. In static samples, the removal of the mixture reached more than 51.9% and in shaken samples, more than 79.2%. Tests using the dead biomass of the fungi only adsorbed up to 37% of the dye mixture (strain BWPH), which suggests that the process with the living biomass involves the biotransformation of the dyes. The best results were reached for the MB strain, which removed 90% of the tested mixture under shaking conditions. Regardless of the efficacy of the dye removal, toxicity decreased from class V to class III in tests with D. magna. Tests with L. minor control samples were classified as class IV, and samples with certain strains were non-toxic. The highest phytotoxicity decrease was noted in shaken samples where the elimination of dye mixture was the best. PMID- 26273257 TI - Isolation of an aryloxyphenoxy propanoate (AOPP) herbicide-degrading strain Rhodococcus ruber JPL-2 and the cloning of a novel carboxylesterase gene (feh). AB - The strain JPL-2, capable of degrading fenoxaprop-P-ethyl (FE), was isolated from the soil of a wheat field and identified as Rhodococcus ruber. This strain could utilize FE as its sole carbon source and degrade 94.6% of 100 mg L(-1) FE in 54 h. Strain JPL-2 could also degrade other aryloxyphenoxy propanoate (AOPP) herbicides. The initial step of the degradation pathway is to hydrolyze the carboxylic acid ester bond. A novel esterase gene feh, encoding the FE hydrolyzing carboxylesterase (FeH) responsible for this initial step, was cloned from strain JPL-2. Its molecular mass was approximately 39 kDa, and the catalytic efficiency of FeH followed the order of FE > quizalofop-P-ethyl > clodinafop propargyl > cyhalofop-butyl > fluazifop-P-butyl > haloxyfop-P-methyl > diclofop methy, which indicated that the chain length of the alcohol moiety strongly affected the hydrolysis activity of the FeH toward AOPP herbicides. PMID- 26273258 TI - Isolation and 2,4-D-degrading characteristics of Cupriavidus campinensis BJ71. AB - An indigenous bacterial strain capable of utilizing 2,4-dichlorophenoxyacetic acid as the sole carbon and energy source was isolated from a soil used for grown wheat with a long-term history of herbicide use in Beijing, China. The strain BJ71 was identified as Cupriavidus campinensis based on its 16S rRNA sequence analysis and morphological, physiological, and biochemical characteristics. The degradation characteristics of strain BJ71 were evaluated. The optimal conditions for 2,4-D degradation were as follows: pH 7.0, 30 degrees C, 3% (v/v) inoculum size, and an initial 2,4-D concentration of 350 mg L(-1). Up to 99.57% of the 2,4 D was degraded under optimal conditions after 6 days of incubation. Strain BJ71 was also able to degrade quizalofop and fluroxypyr. This is the first report of a 2,4-D-degrader containing tfdA gene that can utilize these two herbicides. In a biodegradation experiment, 87.13% and 42.53% of 2,4-D (initial concentration, 350 mg kg(-1)) was degraded in non-sterile and sterilized soil inoculated with BJ71, respectively, after 14 days. The 2,4-D degradation was more rapid in a soil microcosm including BJ71 than in a soil microcosm without BJ71. These results indicate that strain BJ71 is a potential candidate for the bioremediation of soil contaminated with the herbicide 2,4-D. PMID- 26273259 TI - Thermophilic bacteria in Moroccan hot springs, salt marshes and desert soils. AB - The diversity of thermophilic bacteria was investigated in four hot springs, three salt marshes and 12 desert sites in Morocco. Two hundred and forty (240) thermophilic bacteria were recovered, identified and characterized. All isolates were Gram positive, rod-shaped, spore forming and halotolerant. Based on BOXA1R PCR and 16S rRNA gene sequencing, the recovered isolates were dominated by the genus Bacillus (97.5%) represented by B. licheniformis (119), B. aerius (44), B. sonorensis (33), B. subtilis (subsp. spizizenii (2) and subsp. inaquosurum (6)), B. amyloliquefaciens (subsp. amyloliquefaciens (4) and subsp. plantarum (4)), B. tequilensis (3), B. pumilus (3) and Bacillus sp. (19). Only six isolates (2.5%) belonged to the genus Aeribacillus represented by A. pallidus (4) and Aeribacillus sp. (2). In this study, B. aerius and B. tequilensis are described for the first time as thermophilic bacteria. Moreover, 71.25%, 50.41% and 5.41% of total strains exhibited high amylolytic, proteolytic or cellulolytic activity respectively. PMID- 26273260 TI - Biomineralization processes of calcite induced by bacteria isolated from marine sediments. AB - Biomineralization is a known natural phenomenon associated with a wide range of bacterial species. Bacterial-induced calcium carbonate precipitation by marine isolates was investigated in this study. Three genera of ureolytic bacteria, Sporosarcina sp., Bacillus sp. and Brevundimonas sp. were observed to precipitate calcium carbonate minerals. Of these species, Sporosarcina sp. dominated the cultured isolates. B. lentus CP28 generated higher urease activity and facilitated more efficient precipitation of calcium carbonate at 3.24 +/- 0.25 * 10(-4) mg/cell. X-ray diffraction indicated that the dominant calcium carbonate phase was calcite. Scanning electron microscopy showed that morphologies of the minerals were dominated by cubic, rhombic and polygonal plate-like crystals. The dynamic process of microbial calcium carbonate precipitation revealed that B. lentus CP28 precipitated calcite crystals through the enzymatic hydrolysis of urea, and that when ammonium ion concentrations reached 746 mM and the pH reached 9.6, that favored calcite precipitation at a higher level of 96 mg/L. The results of this research provide evidence that a variety of marine bacteria can induce calcium carbonate precipitation, and may influence the marine carbonate cycle in natural environments. PMID- 26273261 TI - Identification of Leptospira serovars by RFLP of the RNA polymerase beta subunit gene (rpoB). AB - Leptospires are usually classified by methods based on DNA-DNA hybridization and the conventional cross-agglutination absorption test, which uses polyclonal antibodies against lipopolysaccharides. In this study, the amplification of the rpoB gene, which encodes the beta-subunit of RNA polymerase, was used as an alternative tool to identify Leptospira. DNA extracts from sixty-eight serovars were obtained, and the hypervariable region located between 1990 and 2500-bp in the rpoB gene was amplified by polymerase chain reaction (PCR). The 600-bp amplicons of the rpoB gene were digested with the restriction endonucleases TaqI, Tru1I, Sau3AI and MslI, and the restriction fragments were separated by 6% polyacrylamide gel electrophoresis. Thirty-five fragment patters were obtained from the combined data of restriction fragment length polymorphism (PCR-RFLP) analysis and used to infer the phylogenetic relationships among the Leptospira species and serovars. The species assignments obtained were in full agreement with the established taxonomic classifications. Twenty-two serovars were effectively identified based on differences in their molecular profiles. However, the other 46 serovars remained clustered in groups that included more than one serovar of different species. This study demonstrates the value of RFLP analysis of PCR-amplified rpoB as an initial method for identifying Leptospira species and serovars. PMID- 26273263 TI - Descriptive study of onychomycosis in a hospital in Sao Paulo. AB - Onychomychosis, a nail fungus infection is the most frequent nail ailment, constituting about half of all nail disorders. It can be caused by dermatophytes, non-dermatophytes, yeasts and Prothoteca spp. Methods include 5407 samples of patients with suspected onychomycosis, studied from January 2002 to December 2006, by direct mycological examination and fungi culture. The diagnosis of onychomycosis was confirmed in samples from 3822 direct mycological and/or culture positive. The diagnosis was established by culture for fungi. Among the 1.428 identified agents, the dermatophytes were responsible for 68.6% (N = 980) of cases, followed by yeasts with 27.6% (N = 394), non-dermatophytes fungi with 2.2% (N = 31), Prothoteca spp with 0.1% (N = 2), and associations with 1.5% (N = 22). Females were more affected, with 66% (N = 2527) of cases, and the most affected age group ranged from 31 to 60 years of age (median 47 years). Fungal microbiota is often changed in the world, both quantitatively and qualitatively, and is affected by several environmental factors. Thus, the periodic review of the composition of this microbiota is important to evaluate the epidemiology and thus proportion a better therapeutic response. PMID- 26273262 TI - Nosocomial candidiasis in Rio de Janeiro State: Distribution and fluconazole susceptibility profile. AB - One hundred and forty-one Candida species isolated from clinical specimens of hospitalized patients in Rio de Janeiro, Brazil, during 2002 to 2007, were analized in order to evaluate the distribution and susceptibility of these species to fluconazole. Candida albicans was the most frequent species (45.4%), followed by C. parapsilosis sensu lato (28.4%), C. tropicalis (14.2%), C. guilliermondii (6.4%), C. famata (2.8%), C. glabrata (1.4%), C. krusei (0.7%) and C. lambica (0.7%). The sources of fungal isolates were blood (47.5%), respiratory tract (17.7%), urinary tract (16.3%), skin and mucous membrane (7.1%), catheter (5.6%), feces (2.1%) and mitral valve tissue (0.7%). The susceptibility test was performed using the methodology of disk-diffusion in agar as recommended in the M44-A2 Document of the Clinical and Laboratory Standards Institute (CLSI). The majority of the clinical isolates (97.2%) was susceptible (S) to fluconazole, although three isolates (2.1%) were susceptible-dose dependent (S-DD) and one of them (0.7%) was resistant (R). The S-DD isolates were C. albicans, C. parapsilosis sensu lato and C. tropicalis. One isolate of C. krusei was resistant to fluconazole. This work documents the high susceptibility to fluconazole by Candida species isolated in Rio de Janeiro, Brazil. PMID- 26273264 TI - Long-term evaluation of the antimicrobial susceptibility and microbial profile of subgingival biofilms in individuals with aggressive periodontitis. AB - This study evaluates the antimicrobial susceptibility and composition of subgingival biofilms in generalized aggressive periodontitis (GAP) patients treated using mechanical/antimicrobial therapies, including chlorhexidine (CHX), amoxicillin (AMX) and metronidazole (MET). GAP patients allocated to the placebo (C, n = 15) or test group (T, n = 16) received full-mouth disinfection with CHX, scaling and root planning, and systemic AMX (500 mg)/MET (250 mg) or placebos. Subgingival plaque samples were obtained at baseline, 3, 6, 9 and 12 months post therapy from 3-4 periodontal pockets, and the samples were pooled and cultivated under anaerobic conditions. The minimum inhibitory concentrations (MICs) of AMX, MET and CHX were assessed using the microdilution method. Bacterial species present in the cultivated biofilm were identified by checkerboard DNA-DNA hybridization. At baseline, no differences in the MICs between groups were observed for the 3 antimicrobials. In the T group, significant increases in the MICs of CHX (p < 0.05) and AMX (p < 0.01) were detected during the first 3 months; however, the MIC of MET decreased at 12 months (p < 0.05). For several species, the MICs significantly changed over time in both groups, i.e., Streptococci MICs tended to increase, while for several periodontal pathogens, the MICs diminished. A transitory increase in the MIC of the subgingival biofilm to AMX and CHX was observed in GAP patients treated using enhanced mechanical therapy with topical CHX and systemic AMX/MET. Both protocols presented limited effects on the cultivable subgingival microbiota. PMID- 26273265 TI - KPC-2-producing Klebsiella pneumoniae in a hospital in the Midwest region of Brazil. AB - The emergence of beta-lactamase-producing Enterobacteriaceae in the last few decades has become major challenge faced by hospitals. In this study, isolates of Klebsiella pneumoniae carbapenemase-2 (KPC-2)-producing K. pneumoniae from a tertiary hospital in Mato Grosso do Sul, Brazil, were characterized. Bacterial identification was performed by matrix-assisted laser desorption/ionization time of-flight (MALDI-TOF; Bruker Daltonics, Germany) mass spectrometry. The minimum inhibitory concentrations of carbapenems were determined using the agar dilution method as recommended by the Clinical Laboratory Standards Institute guidelines. Carbapenemase production was detected using the modified Hodge test (MHT) and polymerase chain reaction (PCR), followed by DNA sequencing. Of 360 (12.2%) K. pneumoniae isolates obtained between May 2009 and May 2010, 44 (12.2%) were carbapenem nonsusceptible. Of these 44 isolates, thirty-six K. pneumoniae isolates that were positive by MHT and PCR carried the bla KPC-2 gene. Thus, KPC 2producing Klebsiella pneumoniae has been present in a Brazilian hospital located in the Midwest region since at least 2009. PMID- 26273266 TI - Prevalence of Helicobacter pylori in children in eastern Turkey and molecular typing of isolates. AB - The objectives of the present study were to determine Helicobacter pylori via culture, polymerase chain reaction and histopathological diagnosis in 101 children ranging in age from 4 to 18 years, to identify the association among restriction fragment length polymorphism types and clinical disease and to investigate the relationships among different isolates of H. pylori in different age groups. We observed a high prevalence of H. pylori infections in children between the ages of 13 and 18 (75.8%), while children aged 4 to 6 years had the lowest prevalence of infection (40%). H. pylori was detected in 30.7% (31 of 101), 66.3% (67 of 101) and 63.2% (60 of 95) of children as determined by culture methods, PCR and histological examination, respectively. H. pylori isolates with RFLP types I and III were the most common among children with antral nodularity, whereas RFLP types II and IV were the least detected types. Interestingly, all isolates from peptic ulcer patients were type III. Although our results show a high prevalence of H. pylori infections in the pediatric population in eastern Turkey, no association was identified between H. pylori infection with antral nodularity and recurring abdominal pain. In addition, we found low genetic variation among H. pylori isolates from children and no association between RFLP types and antral nodularity (p > 0.05). Additionally, we found that H. pylori isolates with specific RFLP types were predominant in different age groups. PMID- 26273267 TI - Seroepidemiology of Paracoccidioides brasiliensis infection in horses from Rio Grande do Sul, Brazil. AB - Paracoccidioides brasiliensis is the etiological agent of the major systemic mycosis in Brazil, called paracoccidioidomycosis. Although the Rio Grande do Sul is considered an endemic area of the disease, there are few studies on the ecology of P. brasiliensis in the state. Therefore, this study aimed to evaluate the infection of P. brasiliensis in horses from the mesoregion of Southwest Riograndense, using these animals as sentinels. Serological techniques, such as double immunodiffusion in agar gel (AGID) and indirect ELISA, were performed to detect the anti-gp43 P. brasiliensis antibody in horses from five different farms in the region of Bage, RS, Brazil. Serology was performed in 200 Pure Blood English horses up to two years of age that were born and raised exclusively at the farms. Of these horses, 12% had anti-gp43 antibodies according to the ELISA results, with rates ranging from 0 to 30% according to the farm of origin (p < 0.001). Based on the immunodiffusion results, all equine serum samples were negative. These results indicate the presence of the fungus P. brasiliensis in the middle region of the southwestern state of Rio Grande do Sul, Brazil. PMID- 26273268 TI - Antimicrobial activity of the essential oil of Tetradenia riparia (Hochst.) Codd. (Lamiaceae) against cariogenic bacteria. AB - In Brazilian folk medicine, Tetradenia riparia (Hochst.) Codd. (Lamiaceae) is used to treat toothaches and dental abscesses and diseases induced by worms, bacteria, or fungi. This paper aims to investigate the chemical composition and the antibacterial effects of the essential oil obtained from Tetradenia riparia leaves (TR-EO) grown in Southeastern Brazil against a representative panel of oral pathogens. We evaluated the antibacterial activity of TR-EO in terms of the minimal inhibitory concentration (MIC). We identified aromadendrene oxide (14.0%), (E,E)-farnesol (13.6%), dronabinol (12.5%), and fenchone (6.2%) as the major constituents of TR-EO. TR-EO displayed MIC values between 31.2 and 500 MUg/mL, with the lowest MIC value being obtained against Streptococcus mitis (31.2 MUg/mL), S. mutans (62.5 MUg/mL), S. sobrinus (31.2 MUg/mL), and Lactobacillus casei (62.5 MUg/mL). In time-kill experiments, TR-EO demonstrated bactericidal activity against S. mutans within the first 12 h, resulting in a curve profile similar to that of chlorhexidine. These results revealed that the essential oil of Tetradenia riparia displays promising activity against most of the selected cariogenic bacteria, including Streptococcus mutans. PMID- 26273269 TI - Invasive infection due to Saprochaete capitata in a young patient with hematological malignancies. AB - We report a case of invasive infection due to Saprochaete capitata in a patient with hematological malignancies after chemotherapy treatment and empiric antifungal therapy with caspofungin. Although severely immunocompromised the patient survived been treated with amphotericin B lipid complex associated with voriconazole. PMID- 26273270 TI - Mannitol-negative methicillin-resistant Staphylococcus aureus from nasal swab specimens in Brazil. AB - The isolation of mannitol-negative methicillin-resistant Staphylococcus aureus from nasal swabs is reported. Among the 59 isolates, 9 (15%) isolates were mannitol-negative; all of these isolates were categorized as staphylococcal cassette chromosome mec (SCCmec) type IVa. This report emphasizes that mannitol fermentation on mannitol salt agar should not be used as the sole criterion when screening nasal swab specimens for S. aureus. PMID- 26273272 TI - Differences in the antimicrobial susceptibility profiles of Moraxella bovis, M. bovoculi and M. ovis. AB - The aim of this study was to determine the differences in the antimicrobial susceptibility profiles of Moraxella bovis, M. bovoculi and M. ovis. Thirty-two strains of Moraxella spp. isolated from cattle and sheep with infectious keratoconjunctivitis were tested via broth microdilution method to determine their susceptibility to ampicillin, cefoperazone, ceftiofur, cloxacillin, enrofloxacin, florfenicol, gentamicin, neomycin, oxytetracycline and penicillin. The results demonstrated that Moraxella spp. strains could be considered sensitive for most of the antimicrobials tested in this study, but differences between the antimicrobial susceptibility profiles of these three Moraxella species were found. M. bovis might differ from other species due to the higher MIC and MBC values it presented. PMID- 26273273 TI - The use of singleplex and nested PCR to detect Batrachochytrium dendrobatidis in free-living frogs. AB - Many microorganisms are able to cause diseases in amphibians, and in the past few years one of the most reported has been Batrachochytrium dendrobatidis. This fungus was first reported in Brazil in 2005; following this, other reports were made in specimens deposited in museum collections, captive and free-living frogs. The aim of this study was to compare singleplex and nested-PCR techniques to detect B. dendrobatidis in free-living and apparently healthy adult frogs from the Brazilian Atlantic Forest. The sample collection area was a protected government park, with no general entrance permitted and no management of the animals there. Swabs were taken from the skin of 107 animals without macroscopic lesions and they were maintained in ethanol p.a. Fungal DNA was extracted and identification of B. dendrobatidis was performed using singleplex and nested-PCR techniques, employing specific primers sequences. B. dendrobatidis was detected in 61/107 (57%) and 18/107 (17%) animals, respectively by nested and singleplex PCR. Nested-PCR was statistically more sensible than the conventional for the detection of B. dendrobatidis (Chi-square = 37.1; alpha = 1%) and the agreement between both techniques was considered just fair (Kappa = 0.27). The high prevalence obtained confirms that these fungi occur in free-living frogs from the Brazilian Atlantic Forest with no macroscopic lesions, characterizing the state of asymptomatic carrier. We concluded that the nested-PCR technique, due to its ease of execution and reproducibility, can be recommended as one of the alternatives in epidemiological surveys to detect B. dendrobatidis in healthy free-living frog populations. PMID- 26273271 TI - Clonal profile, virulence and resistance of Staphylococcus aureus isolated from sheep milk. AB - The objective of this study was to characterize the clonal profile, virulence factors and antimicrobial resistance, particularly oxacillin resistance, of Staphylococcus aureus isolated from sheep milk. Milk samples were collected from all teats for the California Mastitis Test (CMT), somatic cell count, identification of S. aureus, investigation in these strains of genes encoding toxins (sea, seb, sec, sed, tst), biofilm (icaA, icaC, icaD, bap), leukocidin (luk-PV) oxacillin resistance by mecA gene detection and susceptibility testing (12 antibiotics). Messenger RNA expression was evaluated by RT-PCR in isolates carrying toxin and biofilm genes. Biofilm formation was also evaluated phenotypically by adherence to polystyrene plates. The clonal profile of S. aureus was investigated by pulsed-field gel electrophoresis. A total of 473 milk samples were collected from 242 animals on three farms and 20 S. aureus strains were isolated and none carried the mecA gene. The two sec gene-positive isolates and the isolates carrying the tst and luk-PV genes were positive by RT-PCR. Staphylococcus aureus isolated from the three flocks studied showed high susceptibility to the drugs tested and none was biofilm producer, indicating that biofilm formation was not a virulence factor causing infection by these strains. The typing of 17 S. aureus isolates revealed the presence of a common clone on the three farms studied, and the presence and expression of the sec and tst genes in one strain of this clone suggest the possible acquisition of virulence genes by this clone, a fact that is important for animal health and food hygiene. PMID- 26273274 TI - Molecular typing of Argentinian Mycobacterium avium subsp. paratuberculosis isolates by multiple-locus variable number-tandem repeat analysis. AB - Multiple-locus variable number-tandem repeat analysis (MLVA) of Mycobacterium avium subspecies paratuberculosis (MAP) isolates may contribute to the knowledge of strain diversity in Argentina. Although the diversity of MAP has been previously investigated in Argentina using IS900-RFLP, a small number of isolates were employed, and a low discriminative power was reached. The aim of the present study was to test the genetic diversity among MAP isolates using an MLVA approach based on 8 repetitive loci. We studied 97 isolates from cattle, goat and sheep and could describe 7 different patterns: INMV1, INMV2, INMV11, INMV13, INMV16, INMV33 and one incomplete pattern. INMV1 and INMV2 were the most frequent patterns, grouping 76.3% of the isolates. We were also able to demonstrate the coexistence of genotypes in herds and co-infection at the organism level. This study shows that all the patterns described are common to those described in Europe, suggesting an epidemiological link between the continents. PMID- 26273275 TI - Molecular characterization of Brazilian equid herpesvirus type 1 strains based on neuropathogenicity markers. AB - Partial nucleotide sequences of ORF72 (glycoprotein D, gD), ORF64 (infected cell protein 4, ICP4) and ORF30 (DNA polymerase) genes were compared with corresponding sequences of EHV-1 reference strains to characterize the molecular variability of Brazilian strains. Virus isolation assays were applied to 74 samples including visceral tissue, total blood, cerebrospinal fluid (CSF) and nasal swabs of specimens from a total of 64 animals. Only one CSF sample (Iso07/05 strain) was positive by virus isolation in cell culture. EHV-1 Iso07/05 neurologic strain and two abortion visceral tissues samples (Iso11/06 and Iso33/06) were PCR-positive for ORF33 (glycoprotein B, gB) gene of EHV-1. A sequence analysis of the ORF72, ORF64 and ORF30 genes from three EHV-1 archival strains (A3/97, A4/72, A9/92) and three clinical samples (Iso07/05, Iso11/06 and Iso33/06) suggested that among Brazilian EHV-1 strains, the amplified region of the gD gene sequence is highly conserved. Additionally, the analysis of ICP4 gene showed high nucleotide and amino acid identities when compared with genotype P strains, suggesting that the EHV-1 Brazilian strains belonged to the same group. All the EHV-1 Brazilian strains were classified as non-neuropathogenic variants (N752) based on the ORF30 analysis. These findings indicate a high conservation of the gD-, ICP4- and ORF30-encoding sequences. Different pathotypes of the EHV-1 strain might share identical genes with no specific markers, and tissue tropism is not completely dependent on the gD envelope, immediate-early ICP4 and DNA polymerase proteins. PMID- 26273276 TI - Borrelia burgdorferi sensu lato in humans in a rural area of Parana State, Brazil. AB - This study describes the detection of Borrelia garinii and Borrelia burgdorferi sensu stricto (s.s.) in Brazilian individuals using PCR and DNA sequencing. Our results suggest that these species are emerging pathogens in this country, and additional studies are necessary to determine the epidemiological characteristics of this disease in Brazil. PMID- 26273277 TI - In vitro ability of beer fermentation residue and yeast-based products to bind aflatoxin B1. AB - This study aimed to verify the in vitro ability of beer fermentation residue (BFR) containing Saccharomyces cerevisiae cells and five commercial products that differed in the viability and integrity of S. cerevisiae cells to remove aflatoxin B1 (AFB1) from a citrate-phosphate buffer solution (CPBS). BFR was collected at a microbrewery and prepared by drying and milling. The commercial yeast-based products were as follows: inactive intact yeast cells from beer alcoholic fermentation, inactive intact yeast cells from sugarcane alcoholic fermentation, hydrolyzed yeast cells, yeast cell walls and active yeast cells. Adsorption assays were performed in CPBS spiked with 1.0 MUg AFB1/mL at pH 3.0 and 6.0 for a contact time of 60 min at room temperature. Analysis of AFB1 in the samples was performed by high performance liquid chromatography. AFB1 adsorption by the products ranged from 45.5% to 69.4% at pH 3.0 and from 24.0% to 63.8% at pH 6.0. The higher percentages (p < 0.05) of AFB1 binding at both pH values were achieved with products containing hydrolyzed yeast cells or yeast cell walls rather than intact cells. The AFB1 binding percentages of BFR were 55.0 +/- 5.0% at pH 3.0 and 49.2 +/- 4.5% at pH 6.0, which was not significantly different (p > 0.05) from commercial products containing inactive intact yeast cells. The results of this trial indicate that the yeast-based products tested, especially the BFR, have potential applications in animal feeds as a suitable biological method for reducing the adverse effects of aflatoxins. PMID- 26273278 TI - Microbiological quality and safe handling of enteral diets in a hospital in Minas Gerais, Brazil. AB - Contamination of enteral diets represents a high risk of compromising the patient's medical condition. To assess the microbiological quality and aseptic conditions in the preparation and administration of handmade and industrialized enteral diets offered in a hospital in the Valley of Jequitinhonha, MG, Brazil, we performed a microbiological analysis of 50 samples of diets and 27 samples of surfaces, utensils, and water used in the preparation of the diets. In addition, we assessed the good handling practices of enteral diets according to the requirements specified by the Brazilian legislation. Both kinds of enteral diets showed contamination by coliforms and Pseudomonas spp. No sample was positive for Staphylococcus aureus and Salmonella spp. On the other hand, Listeria spp. was detected in only one sample of handmade diets. Contamination was significantly higher in the handmade preparations (p < 0.05). Nonconformities were detected with respect to good handling practices, which may compromise the diet safety. The results indicate that the sanitary quality of the enteral diets is unsatisfactory, especially handmade diets. Contamination by Pseudomonas spp. is significant because it is often involved in infection episodes. With regard to aseptic practices, it was observed the need of implementing new procedures for handling enteral diets. PMID- 26273279 TI - Effect of rosemary essential oil and modified-atmosphere packaging (MAP) on meat quality and survival of pathogens in poultry fillets. AB - The effect of rosemary (Rosmarinus officinalis L.) essential oil (REO) and modified-atmosphere packaging (MAP) on the survival of certain pathogens (Salmonella Typhimurium and Listeria monocytogenes) in poultry fillets and on their meat quality during 7 days of refrigerated storage were investigated. Because REO at 0.05% and 0.1% had weak antibacterial activity and REO at 0.3%, 0.5% and 1.0% imparted unacceptable organoleptic properties, only REO at 0.2% was used to treat the poultry meat. The results showed that adding 0.2% REO to poultry fillets did not reduce the size of the population of S. Typhimurium and L. monocytogenes. However, REO treatment significantly decreased the L* (lightness) value and increased the a* (redness) value of stored fillets, and adding REO in combination with MAP reduced the level of lipid oxidation. In conclusion, in a suitable combination, REO can be applied to improve the quality of meat, but further studies should be conducted to determine the appropriate commercial level for different meat products. PMID- 26273280 TI - Characteristics of dr1790 disruptant and its functional analysis in Deinococcus radiodurans. AB - Deinococcus radiodurans (DR) is an extremophile that is well known for its resistance to radiation, oxidants and desiccation. The gene dr1790 of D. radiodurans was predicted to encode a yellow-related protein. The primary objective of the present study was to characterize the biological function of the DR1790 protein, which is a member of the ancient yellow/major royal jelly (MRJ) protein family, in prokaryotes. Fluorescence labeling demonstrated that the yellow-related protein encoded by dr1790 is a membrane protein. The deletion of the dr1790 gene decreased the cell growth rate and sensitivity to hydrogen peroxide and radiation and increased the membrane permeability of D. radiodurans. Transcript profiling by microarray and RT-PCR analyses of the dr1790 deletion mutant suggested that some genes that are involved in protein secretion and transport were strongly suppressed, while other genes that are involved in protein quality control, such as chaperones and proteases, were induced. In addition, the expression of genes with predicted functions that are involved in antioxidant systems, electron transport, and energy metabolism was significantly altered through the disruption of dr1790. Moreover, the results of proteomic analyses using 2-DE and MS also demonstrated that DR1790 contributed to D. radiodurans survival. Taken together, these results indicate that the DR1790 protein from the ancient yellow protein family plays a pleiotropic role in the survival of prokaryotic cells and contributes to the extraordinary resistance of D. radiodurans against oxidative and radiation stresses. PMID- 26273281 TI - Oleanolic acid and ursolic acid inhibit peptidoglycan biosynthesis in Streptococcus mutans UA159. AB - In this study, we revealed that OA and UA significantly inhibited the expression of most genes related to peptidoglycan biosynthesis in S. mutans UA159. To the best of our knowledge, this is the first report to introduce the antimicrobial mechanism of OA and UA against S. mutans. PMID- 26273282 TI - LAMP technology: Rapid identification of Brucella and Mycobacterium avium subsp. paratuberculosis. AB - In this study, we developed new sets of primers to detect Brucella spp. and M. avium subsp. paratuberculosis (MAP) through isothermal amplification. We selected a previously well-characterized target gene, bscp31, specific for Brucella spp. and IS900 for MAP. The limits of detection using the loop-mediated isothermal amplification (LAMP) protocols described herein were similar to those of conventional PCR targeting the same sequences. Hydroxynaphtol blue and SYBR Green(TM) allowed direct naked-eye detection with identical sensitivity as agarose gel electrophoresis. We included the LAMP-based protocol in a rapid identification scheme of the respective pathogens, and all tested isolates were correctly identified within 2 to 3 h. In addition, both protocols were suitable for specifically identifying the respective pathogens; in the case of Brucella, it also allowed the identification of all the biovars tested. We conclude that LAMP is a suitable rapid molecular typing tool that could help to shorten the time required to identify insidious bacteria in low-complexity laboratories, mainly in developing countries. PMID- 26273283 TI - Platelets can be a biological compartment for the Hepatitis C Virus. AB - Although HCV has hepatic tropism, the presence of the virus in extra-hepatic compartments has been well documented. Platelets have been described as carriers of the virus in the circulation and may be a natural reservoir for the virus. However, few studies have been performed to evaluate the levels of HCV RNA in plasma and platelets are equal or differ in some way. Therefore, the aim of this study was to perform a comparative evaluation of the stability of HCV RNA in plasma and isolated platelets. Four aliquots of whole plasma obtained from patients infected with HCV were incubated at 37 degrees C for 0, 48, 96 and 144 h. After incubation, the plasma and platelet pellet was obtained from each aliquot. Viral RNA in plasma and platelets was quantified by q-PCR. The results showed a decrease in HCV RNA levels in plasma with incubation time. However, platelet HCV RNA levels were stable up to 144 h incubation. The results of this study showed that HCV RNA in platelets, although at lower concentrations than in plasma, is preserved from degradation over time, suggesting that the virus may persist longer in the body when associated with platelets, which could have an impact on the efficiency of antiviral therapy. PMID- 26273284 TI - Enhanced production of prodigiosin by Serratia marcescens MO-1 using ram horn peptone. AB - This work addresses the production of prodigiosin from ram horn peptone (RHP) using MO-1, a local isolate in submerged culture. First, a novel gram-negative and rod-shaped bacterial strain, MO-1, was isolated from the body of the grasshopper (Poecilemon tauricola Ramme 1951), which was collected from pesticide contaminated fields. Sequence analysis of 16S rDNA classified the microbe as Serratia marcescens. The substrate utilization potential (BIOLOG) and fatty acid methyl ester profile (FAME) of S. marcescens were also determined. The effect of RHP on the production of prodigiosin by S. marcescens MO-1 was investigated, and the results showed that RHP supplementation promoted the growth of MO-1 and increased the production of prodigiosin. A concentration of 0.4% (w/v) RHP resulted in the greatest yield of prodigiosin (277.74 mg/L) after 48 h when mannitol was used as the sole source of carbon. The pigment yield was also influenced by the types of carbon sources and peptones. As a result, RHP was demonstrated to be a suitable substrate for prodigiosin production. These results revealed that prodigiosin could be produced efficiently by S. marcescens using RHP. PMID- 26273286 TI - Biological characterization of compounds from Rhinella schneideri poison that act on the complement system. AB - BACKGROUND: The skin secretions of toads of the family Bufonidae contain biogenic amines, alkaloids, steroids (bufotoxins), bufodienolides (bufogenin), peptides and proteins. The poison of Rhinella schneideri, formerly classified as Bufo paracnemis, presents components that act on different biological systems, including the complement system. The aim of this study was to isolate and examine the activity of Rhinella schneideri poison (RsP) components on the complement system. METHODS: The components active on the complement system were purified in three chromatographic steps, using a combination of cation-exchange, anion exchange and gel filtration chromatography. The resulting fractions were analyzed by SDS-PAGE and screened for their activity in the hemolytic assay of the classical/lectin complement pathways. Fractions active on the complement system were also assessed for their ability to generate C3 fragments evaluated by two dimensional immunoelectrophoresis assay, C3a and C5a by neutrophil chemotaxis assay and SC5b-9 complex by ELISA assay. RESULTS: The fractionation protocol was able to isolate the component S5 from the RsP, as demonstrated by SDS-PAGE and the RP-FPLC profile. S5 is a protein of about 6000 Da, while S2 presents components of higher molecular mass (40,000 to 50,000 Da). Fractions S2 and S5 attenuated the hemolytic activity of the classical/lectin pathways after preincubation with normal human serum. Both components stimulated complement dependent neutrophil chemotaxis and the production of C3 fragments, as shown by two-dimensional immunoelectrophoresis. S2 showed a higher capacity to generate the SC5b - 9 complex than the other fractions. This action was observed after the exposure of normal human serum to the fractions. CONCLUSIONS: This is the first study to examine the activity of RsP components on the complement system. Fractions S2 and S5 reduced the complement hemolytic activity, stimulated complement-dependent neutrophil chemotaxis and stimulated the production of C3 fragments, indicating that they were able to activate the complement cascade. Furthermore, fraction S2 was also able to generate the SC5b-9 complex. These components may be useful tools for studying dysfunction of the complement cascade. PMID- 26273285 TI - Arachnids of medical importance in Brazil: main active compounds present in scorpion and spider venoms and tick saliva. AB - Arachnida is the largest class among the arthropods, constituting over 60,000 described species (spiders, mites, ticks, scorpions, palpigrades, pseudoscorpions, solpugids and harvestmen). Many accidents are caused by arachnids, especially spiders and scorpions, while some diseases can be transmitted by mites and ticks. These animals are widely dispersed in urban centers due to the large availability of shelter and food, increasing the incidence of accidents. Several protein and non-protein compounds present in the venom and saliva of these animals are responsible for symptoms observed in envenoming, exhibiting neurotoxic, dermonecrotic and hemorrhagic activities. The phylogenomic analysis from the complementary DNA of single-copy nuclear protein coding genes shows that these animals share some common protein families known as neurotoxins, defensins, hyaluronidase, antimicrobial peptides, phospholipases and proteinases. This indicates that the venoms from these animals may present components with functional and structural similarities. Therefore, we described in this review the main components present in spider and scorpion venom as well as in tick saliva, since they have similar components. These three arachnids are responsible for many accidents of medical relevance in Brazil. Additionally, this study shows potential biotechnological applications of some components with important biological activities, which may motivate the conducting of further research studies on their action mechanisms. PMID- 26273287 TI - Bordonein-L, a new L-amino acid oxidase from Crotalus durissus terrificus snake venom: isolation, preliminary characterization and enzyme stability. AB - BACKGROUND: Crotalus durissus terrificus venom (CdtV) is one of the most studied snake venoms in Brazil. Despite presenting several well known proteins, its L amino acid oxidase (LAAO) has not been studied previously. This study aimed to isolate, characterize and evaluate the enzyme stability of bordonein-L, an LAAO from CdtV. METHODS: The enzyme was isolated through cation exchange, gel filtration and affinity chromatography, followed by a reversed-phase fast protein liquid chromatography to confirm its purity. Subsequently, its N-terminal amino acid sequence was determined by Edman degradation. The enzyme activity and stability were evaluated by a microplate colorimetric assay and the molecular mass was estimated by SDS-PAGE using periodic acid-Schiff staining and determined by mass spectrometry. RESULTS: The first 39 N-terminal amino acid residues exhibited high identity with other snake venom L-amino acid oxidases. Bordonein-L is a homodimer glycoprotein of approximately 101 kDa evaluated by gel filtration. Its monomer presents around 53 kDa estimated by SDS-PAGE and 58,702 Da determined by MALDI-TOF mass spectrometry. The enzyme exhibited maximum activity at pH 7.0 and lost about 50 % of its activity after five days of storage at 4 degrees C. Bordonein-L's activity was higher than the control when stored in 2.8 % mannitol or 8.5 % sucrose. CONCLUSIONS: This research is pioneering in its isolation, characterization and enzyme stability evaluation of an LAAO from CdtV, denominated bordonein-L. These results are important because they increase the knowledge about stabilization of LAAOs, aiming to increase their shelf life. Since the maintenance of enzymatic activity after long periods of storage is essential to enable their biotechnological use as well as their functional studies. PMID- 26273288 TI - Purification procedure for the isolation of a P-I metalloprotease and an acidic phospholipase A2 from Bothrops atrox snake venom. AB - BACKGROUND: Snake venoms are complex mixtures of inorganic and organic components, mainly proteins and peptides. Standardization of methods for isolating bioactive molecules from snake venoms is extremely difficult due to the complex and highly variable composition of venoms, which can be influenced by factors such as age and geographic location of the specimen. Therefore, this study aimed to standardize a simple purification methodology for obtaining a P-I class metalloprotease (MP) and an acidic phospholipase A2 (PLA2) from Bothrops atrox venom, and biochemically characterize these molecules to enable future functional studies. METHODS: To obtain the toxins of interest, a method has been standardized using consecutive isolation steps. The purity level of the molecules was confirmed by RP-HPLC and SDS-PAGE. The enzymes were characterized by determining their molecular masses, isoelectric points, specific functional activity and partial amino acid sequencing. RESULTS: The metalloprotease presented molecular mass of 22.9 kDa and pI 7.4, with hemorrhagic and fibrin(ogen)olytic activities, and its partial amino acid sequence revealed high similarity with other P-I class metalloproteases. These results suggest that the isolated metalloprotease is Batroxase, a P-I metalloprotease previously described by our research group. The phospholipase A2 showed molecular mass of 13.7 kDa and pI 6.5, with high phospholipase activity and similarity to other acidic PLA2s from snake venoms. These data suggest that the acidic PLA2 is a novel enzyme from B. atrox venom, being denominated BatroxPLA2. CONCLUSIONS: The present study successfully standardized a simple methodology to isolate the metalloprotease Batroxase and the acidic PLA2 BatroxPLA2 from the venom of B. atrox, consisting mainly of classical chromatographic processes. These two enzymes will be used in future studies to evaluate their effects on the complement system and the inflammatory process, in addition to the thrombolytic potential of the metalloprotease. PMID- 26273289 TI - Bothrops snake venoms and their isolated toxins, an L-amino acid oxidase and a serine protease, modulate human complement system pathways. AB - BACKGROUND: Activation of the complement system plays an important role in the regulation of immune and inflammatory reactions, and contributes to inflammatory responses triggered by envenomation provoked by Bothrops snakes. The present study aimed to assess whether Bothrops jararacussu and Bothrops pirajai crude venoms and their isolated toxins, namely serine protease (BjussuSP-I) and L-amino acid oxidase (BpirLAAO-I), modulate human complement system pathways. METHODS: Lyophilized venom and toxin samples solubilized in phosphate buffered saline were diluted in appropriate buffers to evaluate their hemolytic activity on the alternative and classical pathways of the complement system. Venom- and toxin treated normal human serum was added to the erythrocyte suspension, and the kinetic of hemolysis was measured spectrophotometrically at 700 nm. The kinetic 96-well microassay format was used for this purpose. We determined the t(1/2) values (time required to lyse 50 % of target erythrocytes), which were employed to calculate the percentage of inhibition of the hemolytic activity promoted by each sample concentration. To confirm complement system activation, complement dependent human neutrophil migration was examined using the Boyden chamber model. RESULTS: At the highest concentration tested (120 MUg/mL), B. jararacussu and B. pirajai crude venoms inhibited the hemolytic activity of the classical pathway (65.3 % and 72.4 %, respectively) more strongly than they suppressed the hemolytic activity of the alternative pathway (14.2 and 13.6 %, respectively). BjussuSP-I (20 MUg/mL) did not affect the hemolytic activity of the classical pathway, but slightly decreased the hemolytic activity of the alternative pathway (13.4 %). BpirLAAO-I (50 MUg/mL) inhibited 24.3 and 12.4 % of the hemolytic activity of the classical and alternative pathways, respectively. Normal human serum treated with B. jararacussu and B. pirajai crude venoms induced human neutrophil migration at a level similar to that induced by zymosan-activated normal human serum. CONCLUSION: Together, the results of the kinetics of hemolysis and the neutrophil chemotaxis assay suggest that pre-activation of the complement system by B. jararacussu and B. pirajai crude venoms consumes complement components and generates the chemotactic factors C3a and C5a. The kinetic microassay described herein is useful to assess the effect of venoms and toxins on the hemolytic activity of the complement system. PMID- 26273290 TI - First serine protease inhibitor isolated from Rhinella schneideri poison. AB - BACKGROUND: Toad secretions are a source of molecules with potential biotechnological application on a wide spectrum of diseases. Toads from the Rhinella family have two kinds of poisonous glands, namely granular and mucous glands. Rhinella schneideri toads produce granular secretions that comprise a great number of molecules, including serine proteases inhibitors. Serine proteases, such as trypsin, chymotrypsin and elastase, are enzymes that have a serine amino acid into its catalytic site and can be found in a large number of vertebrate species and pathogenic microorganisms. Therefore, the present work aims to purify a serine protease inhibitor from Rhinella schneideri granular secretions. FINDINGS: This study presents the protocol used to purify a serine protease inhibitor from the Rhinella schneideri poison. The granular secretion was submitted to dialysis in order to separate the low molecular weight compounds, which were submitted to a reversed phase-fast protein liquid chromatography fractionation step in a C2C18 column. The major fractions were tested over trypsin, chymotrypsin and elastase through colorimetric assay. The inhibition tests were performed with the enzyme in absence (positive control) and presence of fractions, denatured enzyme (negative control) and the respective chromogenic substrate. Rs20 was the compound with the major inhibitory activity over chymotrypsin, inducing a delay in the formation of the chromogenic enzymatic product. The structure characterization of Rs20 was performed by high resolution electronspray ionization-mass spectrometry (HRESI-MS) and gas chromatography coupled with mass spectrometry (GC-MS). HRESI showed an intense signal suggesting the presence of bufadienolide with less than 10 ppm error. In addition, it was observed a low intense signal at m/z 399 that could be lithocholic acid, a biosynthetic precursor of bufadienolide. Finally, GC-MS analysis applying NIST library identification reinforced this hypothesis. CONCLUSIONS: The current study have isolated and partially characterized the function and structure of the first bufadienolide with inhibitory action over chymotrypsin. PMID- 26273291 TI - The Inhibitory Effect of Alisol A 24-Acetate from Alisma canaliculatum on Osteoclastogenesis. AB - Osteoporosis is a disease that decreases bone mass. The number of patients with osteoporosis has been increasing, including an increase in patients with bone fractures, which lead to higher medical costs. Osteoporosis treatment is all important in preventing bone loss. One strategy for osteoporosis treatment is to inhibit osteoclastogenesis. Osteoclasts are bone-resorbing multinucleated cells, and overactive osteoclasts and/or their increased number are observed in bone disorders including osteoporosis and rheumatoid arthritis. Bioactivity-guided fractionations led to the isolation of alisol A 24-acetate from the dried tuber of Alisma canaliculatum. Alisol A 24-acetate inhibited RANKL-mediated osteoclast differentiation by downregulating NFATc1, which plays an essential role in osteoclast differentiation. Furthermore, it inhibited the expression of DC-STAMP and cathepsin K, which are related to cell-cell fusion of osteoclasts and bone resorption, respectively. Therefore, alisol A 24-acetate could be developed as a new structural scaffold for inhibitors of osteoclast differentiation in order to develop new drugs against osteoporosis. PMID- 26273292 TI - Validity of 12-Month Falls Recall in Community-Dwelling Older Women Participating in a Clinical Trial. AB - Objectives. To compare 12-month falls recall with falls reported prospectively on daily falls calendars in a clinical trial of women aged >=70 years. Methods. 2,096 community-dwelling women at high risk of falls and/or fracture completed a daily falls calendar and standardised interviews when falls were recorded, for 12 months. Data were compared to a 12-month falls recall question that categorised falls status as "no falls," "a few times," "several," and "regular" falls. Results. 898 (43%) participants reported a fall on daily falls calendars of whom 692 (77%) recalled fall(s) at 12 months. Participants who did not recall a fall were older (median 79.3 years versus 77.8 years, P = 0.028). Smaller proportions of fallers who sustained an injury or accessed health care failed to recall a fall (all P < 0.04). Among participants who recalled "no fall," 85% reported zero falls on daily calendars. Few women selected falls categories of "several times" or "regular" (4.1% and 0.4%, resp.) and the sensitivity of these categories was low (30% to 33%). Simply categorising participants into fallers or nonfallers had 77% sensitivity and 94% specificity. Conclusion. For studies where intensive ascertainment of falls is not feasible, 12-month falls recall questions with fewer responses may be an acceptable alternative. PMID- 26273293 TI - Association between rs12045440 Polymorphism in the CAPZB Intron and Serum TSH Concentrations in Chinese Thyroid Tumor Patients. AB - The aim of this study was to investigate the possible influence of different genotypes of the lead single nucleotide polymorphisms (SNPs) rs10917468 and rs12045440 in the CAPZB gene on the thyroid function in papillary thyroid carcinoma (PTC) and benign thyroid neoplasm (BN) patients. In the study, a significant association was detected between rs12045440 and serum TSH concentrations in thyroid tumor patients (p = 0.001). After the adjustment of relevant covariates, the difference between the mean serum TSH levels in different genotypes of rs12045440 was still significant in the BN group (p = 0.003) but was not significant in the PTC cases (p = 0.115). No significant association of rs10917468 with TSH levels was found. The SNP rs12045440 was associated with the serum TSH concentrations in Chinese thyroid tumor patients, especially in benign thyroid tumor cases. PMID- 26273294 TI - Micro/Nanostructures and Mechanical Properties of Trabecular Bone in Ovariectomized Rats. AB - Bone mechanical properties encompass both geometric and material factors, while the effects of estrogen deficiency on the material and structural characteristics of bone at micro- to nanoscales are still obscure. We performed a series of combined methodological experiments, including nanoindentation assessment of intrinsic material properties, atomic force microscopy (AFM) characterization of trabecular (Tb) nanostructure, and Tb microarchitecture and 2D BMD. At 15 weeks after surgery, we found significantly less Tb bone mineral density (BMD) at organ (-27%) and at tissue level (-12%), Tb bone volume fraction (-29%), Tb thickness ( 14%), and Tb number (-17%) in ovariectomy (OVX) rats than in sham operated (SHAM) rats, while the structure model index (+91%) and Tb separation (+19%) became significantly greater. AFM images showed lower roughness Tb surfaces with loosely packed large nodular structures and less compacted interfibrillar space in OVX than in SHAM. However, no statistically significant changes were in the Tb intrinsic material properties-nanoindentation hardness, elastic modulus, and plastic deformation-nanoindentation depths, and residual areas. Therefore, estrogen deprivation results in a dramatic deterioration in Tb micro/nanoarchitectures, 3D volumetric BMD at both organ and tissue levels, and 2D BMD, but not in the nanomechanical properties of the trabeculae per se. PMID- 26273296 TI - Elastography Evaluation of Benign Thyroid Nodules in Patients Affected by Hashimoto's Thyroiditis. AB - The aim of the present prospective study was to evaluate the predictive value of elastography in benign thyroid nodules of patients affected by Hashimoto's thyroiditis (HT). From January 2011 to January 2012, 242 nodules in patients affected by HT were submitted to fine needle aspiration cytology (FNAC). All of the patients underwent sonography and elastography performed before FNAC. 230 (95%) nodules were benign, 8 papillary cancers, and 4 follicular lesions. Score 1 was found in 79.1% of benign lesions (sensitivity 79.1%; specificity 66.7%; PPV 97.8%; NPV 14.3%; accuracy 78.5%; p < 0.05). In order to evaluate the outcome of thyroid ultrasound echogenicity in relation to elastography features of nodule(s), all the patients with benign nodules were stratified according to their hypoechoic pattern of thyroid (mild-moderate and severe). Following stratification score 1 was found in 84.2% of benign nodules (sensitivity 75.0%; specificity 88.9%; PPV 27.3%; NPV 98.4%; accuracy 88.2%; p < 0.0001) of patients with a mild-moderate ultrasound thyroid hypoechogenicity, whereas it was found in 60% of benign nodules (p = 0.715) of patients with a marked thyroid hypoechogenicity. Elastography appears to have limited value in detecting thyroid cancer in patients affected by Hashimoto's thyroiditis with severe hypoechoic thyroid tissue. PMID- 26273297 TI - Low Magnesium Exacerbates Osteoporosis in Chronic Kidney Disease Patients with Diabetes. AB - The aim of this study is to investigate the impact of serum Mg on bone mineral metabolism in chronic kidney disease (CKD) patients with or without diabetes. A total of 56 CKD patients not receiving dialysis were recruited and divided into two groups, one group of 27 CKD patients with diabetes and another group of 29 CKD patients without diabetes. Biochemical determinations were made, and the estimated glomerular filtration rate (eGFR) was measured. Bone mineral density was measured by dual-energy X-ray absorptiometry. Serum Mg was inversely correlated with serum Ca (P = 0.023) and positively correlated with serum parathyroid hormone (PTH) (P = 0.020), alkaline phosphatase (P = 0.044), and phosphate (P = 0.040) in the CKD patients with diabetes. The CKD patients with diabetes had lower serum albumin and a higher proportion of hypomagnesemia and osteoporosis than the nondiabetic patients did (P < 0.05). Serum Mg was inversely correlated with eGFR in the CKD patients with or without diabetes (P < 0.05). Serum Mg showed an inverse correlation with 25-hydroxyvitamin D in CKD patients without diabetes (P = 0.006). Furthermore, the diabetic CKD patients with low serum Mg had a lower iPTH (P = 0.007) and a higher serum Ca/Mg ratio (P < 0.001) than the other CKD patients. The lower serum Mg subgroup showed a higher incidence of osteoporosis than the moderate and higher serum Mg subgroups did (66.7%, 39.4%, and 29.4%, resp.). In conclusion, low serum Mg may impact iPTH and exacerbates osteoporosis in CKD patients, particularly with diabetes. PMID- 26273298 TI - Sarco-Osteoporosis: Prevalence and Association with Frailty in Chinese Community Dwelling Older Adults. AB - The aim was to apply AWGS criteria to estimate the prevalence of sarco osteoporosis and investigate its relationship with frailty, in a sample of 316 community-dwelling Chinese older people. Regression analysis was performed using frailty as the dependent variable. The results showed that the prevalence rate of sarco-osteoporosis was 10.4% in older men and 15.1% in older women. ?80 years old (OR 4.8; 95% CI, 3.05-10.76; P = 0.027), women (OR 2.6; 95% CI, 1.18-2.76; P = 0.036), and higher level of comorbidity (OR 3.71; 95% CI, 1.61-10.43; P = 0.021) were independently associated with the likelihood of being sarco-osteoporosis. In the frail group, sarco-osteoporosis occurred in 26.3% of men, in 38.5% of women, and in lower proportion in the prefrail (13.6% of men; 16.2% of women) and nonfrail group (1.6% of men; 1.9% of women) (P < 0.05, resp.). Furthermore, the likelihood of being frail/prefrail was substantially higher in the presence of sarco-osteoporosis (OR 4.16; 95% CI, 2.17-17.65; P = 0.019 in men; and OR 4.67; 95% CI, 2.42-18.86; P = 0.007 in women). The results indicate that patients with sarco-osteoporosis are more likely to be ?80 yrs with higher burden of comorbidities and to have frailty/prefrailty, especially for women. PMID- 26273295 TI - Mechanism and Treatment Strategy of Osteoporosis after Transplantation. AB - Osteoporosis (OP) has emerged as a frequent and devastating complication of organ solid transplantation process. Bone loss after organ transplant is related to adverse effects of immunosuppressants on bone remodeling and bone quality. Many factors contribute to the pathogenesis of OP in transplanted patients. Many mechanisms of OP have been deeply approached. Drugs for OP can be generally divided into "bone resorption inhibitors" and "bone formation accelerators," the former hindering bone resorption by osteoclasts and the latter increasing bone formation by osteoblasts. Currently, bisphosphonates, which are bone resorption inhibitors drugs, are more commonly used clinically than others. Using the signaling pathway or implantation bone marrow stem cell provides a novel direction for the treatment of OP, especially OP after transplantation. This review addresses the mechanism of OP and its correlation with organ transplantation, lists prevention and management of bone loss in the transplant recipient, and discusses the recipients of different age and gender. PMID- 26273299 TI - Effects of Alendronate Sodium Content on the Interface Strengths of Composite Acrylic Bone Cement. AB - Objective. Aim to study how the content of alendronate affected shear strengths at bone-bone cement-metal interfaces. Methods. All samples were divided into 6 groups, G0-G5. On the 1st and 60th day after surgery, bone-bone cement interface shear strengths and bone densities were examined. Interface strengths of metal bone cement specimens were studied before immersion and 4 weeks after immersion. Results. On the 60th day, bone-bone cement interface shear strengths and bone densities showed significant differences (P < 0.05), and compared with G0, G2-G5 values increased significantly (P < 0.05), and the peak value was met in G3. Compared with the 1st day, on the 60th postoperative day both factors decreased significantly in G0 and G1 (P < 0.05). Four weeks after immersion, with the increasing dose of alendronate, the shear strengths decreased gradually and in G5 decreased significantly (P < 0.05). Compared with before immersion, the metal bone cement interface strengths decreased significantly 4 weeks after immersion (P < 0.05). Conclusions. 50-500 mg alendronate in 50 g cement powders could prevent the decrease of shear strengths at bone-bone cement interfaces and had no effect on metal-bone cement interface strengths. While the addition dose was 100 mg, bone cement showed the best strengths. PMID- 26273300 TI - The Clinicopathological Features of BRAF Mutated Papillary Thyroid Cancers in Chinese Patients. AB - The BRAF(V600E) mutation is commonly found in papillary thyroid cancers (PTCs) at different frequencies in different regions. However, the association between the BRAF(V600E) mutation and clinicopathological features in Chinese PTC patients is unknown. A total of 543 Chinese patients with histologically confirmed PTC were enrolled in this study. For the BRAF mutation assay, the target fragments were amplified and sequenced with an ABI 3500 gene analyzer. In 170 of 543 samples (31.3%), the BRAF(V600E) mutation was detected. In the bivariate analysis, the BRAF(V600E) mutation showed an association with bilaterality, tumor size, extrathyroidal invasion, and lymph node metastases (LNM). However, in the multivariate analysis, the BRAF(V600E) mutation was positively related to only tumor size (>1 cm) and extrathyroidal invasion. In addition, the multivariate analysis also showed that the age at diagnosis (<45 y) and tumor size (>1 cm) were independent predictors for LNM. In this study, the BRAF(V600E) mutation is positively associated with worse prognostic factors, including larger tumor size and the tumor extending to the thyroid capsule or extrathyroidal region; however, it is not an independent predictor for LNM. PMID- 26273301 TI - Comparison of the Spine and Hip BMD Assessments Derived from Quantitative Computed Tomography. AB - Quantification of bone mineral density (BMD) is being used as the main method to diagnose osteoporosis. Dual-energy X-ray absorptiometry (DXA) is the most common tools for measuring BMD. Compared to DXA, quantitative computed tomography (QCT) can determine in three dimensions the true volumetric BMD (vBMD) at any skeletal site. In addition to the spine, the hip is an important site for axial BMD measurement. This study examines lumbar spine and hip BMD of Chinese adults by QCT. Age related changes in bone mass derived by QCT measurements were determined. The osteoporosis QCT detection rates at the spine and hip are assessed in both female and male, and agreement of skeletal status category between the spine and hip in older adults is also assessed. PMID- 26273302 TI - Vitamin D and Osteoporosis in HIV/HCV Coinfected Patients: A Literature Review. AB - Vitamin D deficiency further increases the risk of osteoporosis in HIV-positive patients coinfected with hepatitis C virus (HCV); however, it is still unclear whether HCV-related increased fracture risk is a function of the severity of liver disease. The aim of this review was to identify studies on associative vitamin D deficiency patterns in high-risk populations such as HIV/HCV coinfected patients. We did this by searching MEDLINE and EMBASE databases, from inception to August 2014, and included bibliographies. The final 12 articles selected are homogeneous in terms of age but heterogeneous in terms of sample size, participant recruitment, and data source. Most of the HIV/HCV coinfected patients have less than adequate levels of vitamin D. After reviewing the selected articles, we concluded that vitamin D deficiency should be regarded as a continuum and that the lower limit of the ideal range is debatable. We found that vitamin D deficiency might influence liver disease progression in HIV/HCV coinfected patients. Methodological issues in evaluating vitamin D supplementation as a relatively inexpensive therapeutic option are discussed, as well as the need for future research, above all on its role in reducing the risk of HCV-related fracture by modifying liver fibrosis progression. PMID- 26273303 TI - Correlations between Perceived Oral Malodor Levels and Self-Reported Oral Complaints. AB - Objectives. Even though objective data indicating the absence of oral malodor are presented to patients, they may be skeptical about the results, possibly due to the presence of some discomfort in the oral cavity. The objective of this study was to investigate whether there is an association among self-perceptions of oral malodor, oral complaints, and the actual oral malodor test result. Materials and Methods. Questions concerning self-perceptions of oral malodor and subjective intraoral symptoms were extracted from a questionnaire on oral malodor completed by 363 subjects who visited the clinic for oral malodor of Tokyo Dental College Chiba Hospital and gave consent to this study. In addition, the association of self-perception of oral malodor with values obtained after organoleptic and OralChroma measurement was analyzed. Results. No correlation between 195 subjects (54%) who were judged "with oral malodor" (organoleptic score of >=1) and 294 subjects (81.6%) who had a self-perceptions of oral malodor was observed. Self perception of oral malodor was significantly correlated with tongue coating (p = 0.002) and a strange intraoral taste (p = 0.016). Conclusions. Subjects with a self-perception of oral malodor were not necessarily consistent with those actually having an oral malodor. In addition, it was suggested that patients became aware of oral malodor when they felt oral complaints. PMID- 26273304 TI - Regenerative Translation of Human Blood-Vessel-Derived MSC Precursors. AB - Mesenchymal stem/stromal cells (MSCs) represent a promising adult progenitor cell source for tissue repair and regeneration. Their mysterious identity in situ has gradually been unveiled by the accumulating evidence indicating an association between adult multipotent stem/progenitor cells and vascular/perivascular niches. Using immunohistochemistry and fluorescence-activated cell sorting, we and other groups have prospectively identified and purified subpopulations of multipotent precursor cells associated with the blood vessels within multiple human organs. The three precursor subsets, myogenic endothelial cells (MECs), pericytes (PCs), and adventitial cells (ACs), are located, respectively, in the three structural tiers of typical blood vessels: intima, media, and adventitia. MECs, PCs, and ACs have been extensively characterized in prior studies and are currently under investigation for their therapeutic potentials in preclinical animal models. In this review, we will briefly discuss the identification, isolation, and characterization of these human blood-vessel-derived stem cells (hBVSCs) and summarize the current status of regenerative applications of hBVSC subsets. PMID- 26273305 TI - Adult Mesenchymal Stem Cells: When, Where, and How. AB - Adult mesenchymal stem cells (MSCs) have profound medicinal effects at body sites of tissue injury, disease, or inflammation as either endogenously or exogenously supplied. The medicinal effects are either immunomodulatory or trophic or both. When to deliver these mediators of regeneration, where, and by what delivery apparatus or mechanism will directly determine their medical efficacy. The MSCs help manage the innate regenerative capacity of almost every body tissue and the MSCs have only recently been fully appreciated. Perhaps the most skilled physician-manager of the body's innate regenerative capacity is in orthopedics where the vigorous regeneration and repair capacity of bone through local MSCs titers is expertly managed by the orthopaedic physician. The challenge is to extend MSCs expertise to address other tissue dysfunctions and diseases. The medicine of tomorrow will encompass optimizing the tissues' intrinsic regenerative potential through management of local MSCs. PMID- 26273306 TI - Modulation of Hyaluronan Synthesis by the Interaction between Mesenchymal Stem Cells and Osteoarthritic Chondrocytes. AB - Bone marrow mesenchymal stem cells (BM-MSCs) are considered a good source for cellular therapy in cartilage repair. But, their potential to repair the extracellular matrix, in an osteoarthritic environment, is still controversial. In osteoarthritis (OA), anti-inflammatory action and extracellular matrix production are important steps for cartilage healing. This study examined the interaction of BM-MSC and OA-chondrocyte on the production of hyaluronan and inflammatory cytokines in a Transwell system. We compared cocultured BM-MSCs and OA-chondrocytes with the individually cultured controls (monocultures). There was a decrease in BM-MSCs cell count in coculture with OA-chondrocytes when compared to BM-MSCs alone. In monoculture, BM-MSCs produced higher amounts of hyaluronan than OA-chondrocytes and coculture of BM-MSCs with OA-chondrocytes increased hyaluronan production per cell. Hyaluronan synthase-1 mRNA expression was upregulated in BM-MSCs after coculture with OA-chondrocytes, whereas hyaluronidase-1 was downregulated. After coculture, lower IL-6 levels were detected in BM-MSCs compared with OA-chondrocytes. These results indicate that, in response to coculture with OA-chondrocytes, BM-MSCs change their behavior by increasing production of hyaluronan and decreasing inflammatory cytokines. Our results indicate that BM-MSCs per se could be a potential tool for OA regenerative therapy, exerting short-term effects on the local microenvironment even when cell:cell contact is not occurring. PMID- 26273307 TI - Bottlenecks in the Efficient Use of Advanced Therapy Medicinal Products Based on Mesenchymal Stromal Cells. AB - Mesenchymal stromal cells (MSCs) have been established as promising candidate sources of universal donor cells for cell therapy due to their contributions to tissue and organ homeostasis, repair, and support by self-renewal and multidifferentiation, as well as by their anti-inflammatory, antiproliferative, immunomodulatory, trophic, and proangiogenic properties. Various diseases have been treated by MSCs in animal models. Additionally, hundreds of clinical trials related to the potential benefits of MSCs are in progress. However, although all MSCs are considered suitable to exert these functions, dissimilarities have been found among MSCs derived from different tissues. The same levels of efficacy and desired outcomes have not always been achieved in the diverse studies that have been performed thus far. Moreover, autologous MSCs can be affected by the disease status of patients, compromising their use. Therefore, collecting information regarding the characteristics of MSCs obtained from different sources and the influence of the host (patient) medical conditions on MSCs is important for assuring the safety and efficacy of cell-based therapies. This review provides relevant information regarding factors to consider for the clinical application of MSCs. PMID- 26273308 TI - Multipotent Mesenchymal Stromal Cells: Possible Culprits in Solid Tumors? AB - The clinical use of bone marrow derived multipotent mesenchymal stromal cells (BM MSCs) in different settings ranging from tissue engineering to immunotherapies has prompted investigations on the properties of these cells in a variety of other tissues. Particularly the role of MSCs in solid tumors has been the subject of many experimental approaches. While a clear phenotypical distinction of tumor associated fibroblasts (TAFs) and MSCs within the tumor microenvironment is still missing, the homing of bone marrow MSCs in tumor sites has been extensively studied. Both, tumor-promoting and tumor-inhibiting effects of BM-MSCs have been described in this context. This ambiguity requires a reappraisal of the different studies and experimental methods employed. Here, we review the current literature on tumor-promoting and tumor-inhibiting effects of BM-MSCs with a particular emphasis on their interplay with components of the immune system and also highlight a potential role of MSCs as cell of origin for certain mesenchymal tumors. PMID- 26273310 TI - A Survey of Residents' Perceptions of the Effect of Large-Scale Economic Developments on Perceived Safety, Violence, and Economic Benefits. AB - BACKGROUND: Emerging research highlights the promise of community- and policy level strategies in preventing youth violence. Large-scale economic developments, such as sports and entertainment arenas and casinos, may improve the living conditions, economics, public health, and overall wellbeing of area residents and may influence rates of violence within communities. OBJECTIVE: To assess the effect of community economic development efforts on neighborhood residents' perceptions on violence, safety, and economic benefits. METHODS: Telephone survey in 2011 using a listed sample of randomly selected numbers in six Pittsburgh neighborhoods. Descriptive analyses examined measures of perceived violence and safety and economic benefit. Responses were compared across neighborhoods using chi-square tests for multiple comparisons. Survey results were compared to census and police data. RESULTS: Residents in neighborhoods with the large-scale economic developments reported more casino-specific and arena-specific economic benefits. However, 42% of participants in the neighborhood with the entertainment arena felt there was an increase in crime, and 29% of respondents from the neighborhood with the casino felt there was an increase. In contrast, crime decreased in both neighborhoods. CONCLUSIONS: Large-scale economic developments have a direct influence on the perception of violence, despite actual violence rates. PMID- 26273309 TI - Low Reactive Level Laser Therapy for Mesenchymal Stromal Cells Therapies. AB - Low reactive level laser therapy (LLLT) is mainly focused on the activation of intracellular or extracellular chromophore and the initiation of cellular signaling by using low power lasers. Over the past forty years, it was realized that the laser therapy had the potential to improve wound healing and reduce pain and inflammation. In recent years, the term LLLT has become widely recognized in the field of regenerative medicine. In this review, we will describe the mechanisms of action of LLLT at a cellular level and introduce the application to mesenchymal stem cells and mesenchymal stromal cells (MSCs) therapies. Finally, our recent research results that LLLT enhanced the MSCs differentiation to osteoblast will also be described. PMID- 26273311 TI - Zuogui Jiangtang Jieyu Formulation Prevents Hyperglycaemia and Depressive-Like Behaviour in Rats by Reducing the Glucocorticoid Level in Plasma and Hippocampus. AB - Aim. To determine whether Zuogui Jiangtang Jieyu prescription (ZGJTJY) has hypoglycemic and antidepressant effects which are mediated by corticosterone through adjustment of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) and glucocorticoid (GR) levels. Materials and Methods. The diabetes-related depression rats were randomly divided into four groups: the model group, metformin (1.8 mg/kg) combined with fluoxetine (10.8 mg/kg) group, and ZGJTJY high and low dose groups. Four weeks after modeling, blood glucose, behavior, and cognitive function of depression were detected. The expressions of 11beta-HSD1 and GR in hippocampus were measured by western blotting and immunohistochemical experiments. Results. We found that (1) the treatment with ZGJTJY (10.26 g/kg) increases the motor activities and improves cognition ability. (2) ZGJTJY (10.26 g/kg) significantly relieves the disorder in blood and the relative indexes. (3) ZGJTJY (10.26 g/kg) can reduce hippocampal corticosterone expression levels and further improve hippocampus pathological changes. (4) ZGJTJY increased the expression of GR accompanied with decreasing 11beta-HSD1 in hippocampus. Conclusions. ZGJTJY inhibits the expression of 11beta-HSD1 and increases GR in hippocampus and subsequently modulates blood glucose levels, and therefore it is potential property that ZGJTJY could be of benefit for the treatment of behavior and cognitive function of diabetes-related depression. PMID- 26273312 TI - Si Shen Wan Regulates Phospholipase Cgamma-1 and PI3K/Akt Signal in Colonic Mucosa from Rats with Colitis. AB - The present study explored the feasible pathway of Si Shen Wan (SSW) in inhibiting apoptosis of intestinal epithelial cells (IECs) by observing activation of phospholipase Cgamma-1 (PLC-gamma1) and PI3K/Akt signal in colonic mucosa from rats with colitis. Experimental colitis was induced by 2,4,6 trinitrobenzene sulfonic acid (TNBS) in the Sprague-Dawley rats. After SSW was administrated for 7 days after TNBS infusion, western blot showed an increment in levels of PI3K, p-Akt, and IL-23 and a decrement in levels of PLC-gamma1 and HSP70 in colonic mucosal injury induced by TNBS. Meanwhile, assessments by ELISA revealed an increment in concentrations of IL-2, IL-6, and IL-17 and a reduction in level of TGF-beta after TNBS challenge. Impressively, treatment with SSW for 7 days significantly attenuated the expressions of PI3K and p-Akt and the secretion of IL-2, IL-6, IL-17, and IL-23 and promoted the activation of PLC-gamma1, HSP70, and TGF-beta. Our previous studies had demonstrated that SSW restored colonic mucosal ulcers by inhibiting apoptosis of IECs. The present study demonstrated that the effect of SSW on inhibiting apoptosis of IECs was realized probably by activation of PLC-gamma1 and suppression of PI3K/Akt signal pathway. PMID- 26273313 TI - Complementary Therapies for Idiopathic Hirsutism: Topical Licorice as Promising Option. AB - Hirsutism is one of the most prevalent health problems in women. The aim of the study was to compare the effect of 755 nm alexandrite hair removal laser with that of alexandrite laser plus topical licorice on the improvement of idiopathic hirsutism. A double-blind, randomized placebo-controlled study was performed on 90 female subjects. The patients were divided into two groups: alexandrite laser plus 15% licorice gel (group A) and placebo (group B). Each subject received one of both products over one side of the face, twice daily for 24 weeks on the hirsute locations. Each group underwent five sessions of alexandrite laser at 6 week intervals. To minimize the effects of confounding variables, the test was performed on two separate zones of patients' skin. The mean +/- SD numbers of terminal hairs in group A were 7.05 +/- 4.55 for zone 1 and 6.06 +/- 3.70 for zone 2. In group B, they were 3.18 +/- 1.75 for zone 1 and 2.49 +/- 1.63 for zone 2. The difference in the mean number of terminal hairs was statistically significant between the two groups (p < 0.001), and there were no serious adverse reactions. The treatment of idiopathic hirsutism with 755 nm alexandrite laser plus topical licorice is more effective than alexandrite laser only. PMID- 26273314 TI - Allium cepa L. and Quercetin Inhibit RANKL/Porphyromonas gingivalis LPS-Induced Osteoclastogenesis by Downregulating NF-kappaB Signaling Pathway. AB - Objectives. We evaluated the in vitro modulatory effects of Allium cepa L. extract (AcE) and quercetin (Qt) on osteoclastogenesis under inflammatory conditions (LPS-induced). Methods. RAW 264.7 cells were differentiated with 30 ng/mL of RANKL, costimulated with PgLPS (1 ug/mL), and treated with AcE (50-1000 ug/mL) or Qt (1.25, 2.5, or 5 uM). Cell viability was determined by alamarBlue and protein assays. Nuclei morphology was analysed by DAPI staining. TRAP assays were performed as follows: p-nitrophenyl phosphate was used to determine the acid phosphatase activity of the osteoclasts and TRAP staining was used to evaluate the number and size of TRAP-positive multinucleated osteoclast cells. Von Kossa staining was used to measure osteoclast resorptive activity. Cytokine levels were measured on osteoclast precursor cell culture supernatants. Using western blot analysis, p-IkappaBalpha and IkappaBalpha degradation, inhibitor of NF-kappaB, were evaluated. Results. Both AcE and Qt did not affect cell viability and significantly reduced osteoclastogenesis compared to control. We observed lower production of IL-6 and IL-1alpha and an increased production of IL-3 and IL-4. AcE and Qt downregulated NF-kappaB pathway. Conclusion. AcE and Qt may be inhibitors of osteoclastogenesis under inflammatory conditions (LPS-induced) via attenuation of RANKL/PgLPS-induced NF-kappaB activation. PMID- 26273315 TI - Central Antinociceptive and Mechanism of Action of Pereskia bleo Kunth Leaves Crude Extract, Fractions, and Isolated Compounds. AB - Pereskia bleo (Kunth) DC. (Cactaceae) is a plant commonly used in popular medicine in Malaysia. In this work, we evaluate the antinociceptive effect of P. bleo leaf extracts and isolated compounds in central antinociceptive model. Ethanol extract (E), hexane (H), ethyl acetate (EA), or butanol (B) fractions (30, 50, or 100 mg/kg, p.o.), sitosterol (from hexane) and vitexin (from ethyl acetate), were administered to mice. Antinociceptive effect was evaluated in the hot plate and capsaicin- or glutamate-induced licking models. Morphine (1 mg/kg, p.o.) was used as reference drug. Naloxone (1 mg/kg, i.p.), atropine (1 mg/kg, i.p.), and L-nitro arginine methyl ester (L-NAME, 3 mg/kg, i.p.) were administered 30 min earlier (100 mg/kg, p.o.) in order to evaluate the mechanism of the antinociceptive action. Higher dose of B developed an effect significantly superior to morphine-treated group. Naloxone prevented the antinociceptive effect of all fractions. L-NAME demonstrated effect against E, EA, and B. In all fractions, sitosterol and vitexin reduced the licking time after capsaicin injection. Glutamate-induced licking response was blocked by H, EA, and B. Our results indicate that Pereskia bleo fractions, sitosterol and vitexin, possessed a central antinociceptive effect. Part of this effect is mediated by opioid receptors and nitrergic pathway. PMID- 26273316 TI - Swertianlarin, an Herbal Agent Derived from Swertia mussotii Franch, Attenuates Liver Injury, Inflammation, and Cholestasis in Common Bile Duct-Ligated Rats. AB - Swertianlarin is an herbal agent abundantly distributed in Swertia mussotii Franch, a Chinese traditional herb used for treatment of jaundice. To study the therapeutic effect of swertianlarin on cholestasis, liver injury, serum proinflammatory cytokines, and bile salt concentrations were measured by comparing rats treated with swertianlarin 100 mg/kg/d or saline for 3, 7, or 14 days after bile duct ligation (BDL). Serum alanine aminotransferase (ATL) and aspartate aminotransferase (AST) levels were significantly decreased in BDL rats treated with swertianlarin for 14 days (P < 0.05). The reduced liver injury in BDL rats by swertianlarin treatment for 14 days was further confirmed by liver histopathology. Levels of serum tumor necrosis factor alpha (TNFalpha) were decreased by swertianlarin in BDL rats for 3 and 7 days (P < 0.05). Moreover, reductions in serum interleukins IL-1beta and IL-6 levels were also observed in BDL rats treated with swertianlarin (P < 0.05). In addition, most of serum toxic bile salt concentrations (e.g., chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA)) in cholestatic rats were decreased by swertianlarin (P < 0.05). In conclusion, the data suggest that swertianlarin derived from Swertia mussotii Franch attenuates liver injury, inflammation, and cholestasis in bile duct ligated rats. PMID- 26273317 TI - Serum Pharmacochemistry Analysis Using UPLC-Q-TOF/MS after Oral Administration to Rats of Shenfu Decoction. AB - The purpose of this study was to study the serum pharmacochemistry of SFD as well as the material basis through analyzing the constituents absorbed in blood. The SFD was orally administrated to Wistar rats at 20 g.kg(-1), and Ultra Performance Liquid Chromatography (UPLC) fingerprints of SFD were created. Serum samples were collected for analysis, and further data processing used MarkerLynx XS software. 19 ginsenosides and 16 alkaloids were detected in SFD. The absorption of alkaloids (mainly monoester diterpenoid alkaloids) increased when Aconitum carmichaeli Debx. was combined with Panax ginseng, while the ginsenosides remained stable. Diester diterpenoid alkaloids were not present in the serum samples. A suitable serum pharmacochemistry method was successfully established to study pharmacological effects and potential improvements in formulation. This may also be useful for toxicity reduction. We suspect that the increased absorption of the monoester diterpenoid alkaloids from the mixture of Panax and Radix, compared to the Panax only extract, may be the reason for the combination of the two herbs in popular medicine formulas in China. PMID- 26273318 TI - Epidemiology of anorexia nervosa in Japanese adolescents. AB - BACKGROUND: No epidemiologic survey examining eating disorders in Japan has been done at a national level since 1992. The prevalence of anorexia nervosa, as assessed by questionnaires to hospitals, is thought to be underestimated because patients with anorexia nervosa tend to avoid consultations. In conformity with the School Health and Safety Act of Japan, schools are required to have physicians perform a medical examination of students every year. The teachers in charge of health education and school physicians determine the height, weight, and health condition, and examine the medical records of each student. Therefore, we as members of the Survey Committee for Eating Disorders of the Japanese Ministry of Health, Labour, and Welfare conducted an epidemiologic survey using questionnaires sent to schools in seven prefectures to determine the current prevalence of anorexia nervosa among adolescents. METHODS: We sent a questionnaire to elementary, junior high, and senior high schools. Questionnaires contained items on the number of students, patients with anorexia nervosa in each grade who were diagnosed by specialists, and students who the school physician strongly suspected to have anorexia nervosa but who did not undergo a clinical examination in a medical institution. RESULTS: We found patients of both sexes with anorexia nervosa aged 9-10 years in elementary schools. The point prevalence of anorexia nervosa for girls, including strongly suspected cases, in the three grades of junior high school and three grades of senior high school were 0-0.17 %, 0-0.21 %, 0.17-0.40 %, 0.05-0.56 %, 0.17-0.42 % and 0.09-0.43 %, respectively. We also confirmed a prominent sex difference in the prevalence of anorexia nervosa. The prevalence of boys was one third that of girls in some prefectures. One third to one half of diagnosed and strongly suspected students with anorexia nervosa had not received medical consultation or treatment. CONCLUSIONS: Although the prevalence of anorexia nervosa had regional differences in Japan, it has reached levels comparable to those in Western societies. Because no eating disorder center exists and the treatment environment is poor, national action to address this disease is a pressing need in Japan. PMID- 26273320 TI - Bioelectrochemical production of hydrogen in an innovative pressure-retarded osmosis/microbial electrolysis cell system: experiments and modeling. AB - BACKGROUND: While microbial electrolysis cells (MECs) can simultaneously produce bioelectrochemical hydrogen and treat wastewater, they consume considerable energy to overcome the unfavorable thermodynamics, which is not sustainable and economically feasible in practical applications. This study presents a proof-of concept system in which hydrogen can be produced in an MEC powered by theoretically predicated energy from pressure-retarded osmosis (PRO). The system consists of a PRO unit that extracts high-quality water and generates electricity from water osmosis, and an MEC for organic removal and hydrogen production. The feasibility of the system was demonstrated using simulated PRO performance (in terms of energy production and effluent quality) and experimental MEC results (e.g., hydrogen production and organic removal). RESULTS: The PRO and MEC models were proven to be valid. The model predicted that the PRO unit could produce 485 mL of clean water and 579 J of energy with 600 mL of draw solution (0.8 M of NaCl). The amount of the predicated energy was applied to the MEC by a power supply, which drove the MEC to remove 93.7 % of the organic compounds and produce 32.8 mL of H2 experimentally. Increasing the PRO influent volume and draw concentration could produce more energy for the MEC operation, and correspondingly increase the MEC hydraulic retention time (HRT) and total hydrogen production. The models predicted that at an external voltage of 0.9 V, the MEC energy consumption reached the maximum PRO energy production. With a higher external voltage, the MEC energy consumption would exceed the PRO energy production, leading to negative effects on both organic removal and hydrogen production. CONCLUSIONS: The PRO-MEC system holds great promise in addressing water-energy nexus through organic removal, hydrogen production, and water recovery: (1) the PRO unit can reduce the volume of wastewater and extract clean water; (2) the PRO effluents can be further treated by the MEC; and (3) the osmotic energy harvested from the PRO unit can be applied to the MEC for sustainable bioelectrochemical hydrogen production. PMID- 26273319 TI - Transcriptional analysis of Kluyveromyces marxianus for ethanol production from inulin using consolidated bioprocessing technology. AB - BACKGROUND: Ethanol production from non-crop materials, such as Jerusalem artichokes, would make a great contribution to the energy industry. The non conventional yeast, Kluyveromyces marxianus, is able to carry out ethanol fermentation of sugar molecules obtained from inulin-containing materials by consolidated bioprocessing. Lower inulin concentrations and micro-aeration can lead to a relatively fast and ideal fermentation process; however, it is unclear what causes the inhibition of higher concentrations of inulin and the promotion effect of aeration. RESULTS: Next-generation sequencing technology was used to study the global transcriptional response of K. marxianus Y179 under three fermentation conditions, including 120 g/L inulin without aeration (120-N), 230 g/L inulin without aeration (230-N), 230 g/L inulin with aeration by ORP controlling at -130 mV (230-130mV). A total of 35.55 million clean reads were generated from three samples, of which 4,820 predicted that open reading frames were annotated. For differential expression analysis, 950 and 1,452 differentially expressed genes were discovered under the conditions of 230-130mV and 120-N, respectively, and the sample 230-N was used as the control. These genes are mainly associated with the pathways of central carbon metabolism and ethanol formation. Increased expression of inulinase and the low activity of the autophagy-related gene, ATG8, ensured fast and ideal fermentation processes. CONCLUSIONS: Despite being reported as the "crabtree-negative" species, K. marxianus Y179 could achieve favorable ethanol fermentation profiles under micro aeration and high inulin concentrations. K. marxianus Y179 cells responded to inulin concentrations and micro-aeration that is involved in the whole ethanol metabolism network. These results will serve as an important foundation for further exploration of the regulatory mechanisms involved in ethanol fermentation from inulin by consolidated bioprocessing and also provide a valuable reference for future studies on optimization and reconstruction of the metabolism network in K. marxianus. PMID- 26273321 TI - Simultaneous utilization of glucose and xylose for lipid accumulation in black soldier fly. AB - BACKGROUND: Lignocellulose is known to be an abundant source of glucose and xylose for biofuels. Yeasts can convert glucose into bioethanol. However, bioconversion of xylose by yeasts is not very efficient, to say nothing of the presence of both glucose and xylose. Efficient utilization of xylose is one of the critical factors for reducing the cost of biofuel from lignocelluloses. However, few natural microorganisms preferentially convert xylose to ethanol. The simultaneous utilization of both glucose and xylose is the pivotal goal in the production of biofuels. RESULTS: In this paper, we found that 97.3 % of the glucose and 93.8 % of the xylose in our experiments was consumed by black soldier fly (BSF) simultaneously. The content of lipid reached its highest level (34.60 %) when 6 % xylose was added into the standard feed. 200 g of rice straw was pretreated with 1 % KOH, followed by enzymatic hydrolysis for fermentation of ethanol, the residue from this fermentation was then fed to BSF for lipid accumulation. In total, 10.9 g of bioethanol and 4.3 g of biodiesel were obtained. CONCLUSIONS: The results of this study suggest that BSF is a very promising organism for use in converting lignocellulose into lipid for biodiesel production. PMID- 26273322 TI - Reversing chromatin accessibility differences that distinguish homologous mitotic metaphase chromosomes. AB - BACKGROUND: Chromatin-modifying reagents that alter histone associating proteins, DNA conformation or its sequence are well established strategies for studying chromatin structure in interphase (G1, S, G2). Little is known about how these compounds act during metaphase. We assessed the effects of these reagents at genomic loci that show reproducible, non-random differences in accessibility to chromatin that distinguish homologous targets by single copy DNA probe fluorescence in situ hybridization (scFISH). By super-resolution 3-D structured illumination microscopy (3D-SIM) and other criteria, the differences correspond to 'differential accessibility' (DA) to these chromosomal regions. At these chromosomal loci, DA of the same homologous chromosome is stable and epigenetic hallmarks of less accessible interphase chromatin are present. RESULTS: To understand the basis for DA, we investigate the impact of epigenetic modifiers on these allelic differences in chromatin accessibility between metaphase homologs in lymphoblastoid cell lines. Allelic differences in metaphase chromosome accessibility represent a stable chromatin mark on mitotic metaphase chromosomes. Inhibition of the topoisomerase IIalpha-DNA cleavage complex reversed DA. Inter homolog probe fluorescence intensity ratios between chromosomes treated with ICRF 193 were significantly lower than untreated controls. 3D-SIM demonstrated that differences in hybridized probe volume and depth between allelic targets were equalized by this treatment. By contrast, DA was impervious to chromosome decondensation treatments targeting histone modifying enzymes, cytosine methylation, as well as in cells with regulatory defects in chromatid cohesion. These data altogether suggest that DA is a reflection of allelic differences in metaphase chromosome compaction, dictated by the localized catenation state of the chromosome, rather than by other epigenetic marks. CONCLUSIONS: Inhibition of the topoisomerase IIalpha-DNA cleavage complex mitigated DA by decreasing DNA superhelicity and axial metaphase chromosome condensation. This has potential implications for the mechanism of preservation of cellular phenotypes that enables the same chromatin structure to be correctly reestablished in progeny cells of the same tissue or individual. PMID- 26273323 TI - Apoptosis induction by combination of drugs or a conjugated molecule associating non-steroidal anti-inflammatory and nitric oxide donor effects in medullary thyroid cancer models: implication of the tumor suppressor p73. AB - BACKGROUND: Medullary thyroid cancer (MTC) is a C-cell neoplasm. Surgery remains its main treatment. Promising therapies based on tyrosine kinase inhibitors demand careful patient selection. We previously observed that two non-steroidal anti-inflammatory drugs (NSAID), indomethacin, celecoxib, and nitric oxide (NO) prevented tumor growth in a model of human MTC cell line (TT) in nude mice. METHODS: In the present study, we tested the NO donor: glyceryl trinitrate (GTN), at pharmacological dose, alone and in combination with each of the two NSAIDs on TT cells. We also assessed the anti-proliferative potential of NO-indomethacin, an indomethacin molecule chemically conjugated with a NO moiety (NCX 530, Nicox SA) on TT cells and indomethacin/GTN association in rMTC 6-23 cells. The anti tumoral action of the combined sc. injections of GTN with oral delivery of indomethacin was also studied on subcutaneous TT tumors in nude mice. Apoptosis mechanisms were assessed by expression of caspase-3, TAp73alpha, TAp73alpha inhibition by siRNA or Annexin V externalisation. RESULTS: The two NSAIDs and GTN reduced mitotic activity in TT cells versus control (cell number and PCNA protein expression). The combined treatments amplified the anti-tumor effect of single agents in the two tested cell lines and promoted cell death. Moreover, indomethacin/GTN association stopped the growth of established TT tumors in nude mice. We observed a significant cleavage of full length PARP, a caspase-3 substrate. The cell death appearance was correlated with a two-fold increase in TAp73alpha expression, with inhibition of apoptosis after TAp73alpha siRNA addition, demonstrating its crucial role in apoptosis. CONCLUSION: Association of NO with NSAID exhibited amplified anti-tumoral effects on in vitro and in vivo MTC models by inducing p73-dependent apoptotic cell death. PMID- 26273325 TI - Robust optimization of SVM hyperparameters in the classification of bioactive compounds. AB - BACKGROUND: Support Vector Machine has become one of the most popular machine learning tools used in virtual screening campaigns aimed at finding new drug candidates. Although it can be extremely effective in finding new potentially active compounds, its application requires the optimization of the hyperparameters with which the assessment is being run, particularly the C and [Formula: see text] values. The optimization requirement in turn, establishes the need to develop fast and effective approaches to the optimization procedure, providing the best predictive power of the constructed model. RESULTS: In this study, we investigated the Bayesian and random search optimization of Support Vector Machine hyperparameters for classifying bioactive compounds. The effectiveness of these strategies was compared with the most popular optimization procedures-grid search and heuristic choice. We demonstrated that Bayesian optimization not only provides better, more efficient classification but is also much faster-the number of iterations it required for reaching optimal predictive performance was the lowest out of the all tested optimization methods. Moreover, for the Bayesian approach, the choice of parameters in subsequent iterations is directed and justified; therefore, the results obtained by using it are constantly improved and the range of hyperparameters tested provides the best overall performance of Support Vector Machine. Additionally, we showed that a random search optimization of hyperparameters leads to significantly better performance than grid search and heuristic-based approaches. CONCLUSIONS: The Bayesian approach to the optimization of Support Vector Machine parameters was demonstrated to outperform other optimization methods for tasks concerned with the bioactivity assessment of chemical compounds. This strategy not only provides a higher accuracy of classification, but is also much faster and more directed than other approaches for optimization. It appears that, despite its simplicity, random search optimization strategy should be used as a second choice if Bayesian approach application is not feasible.Graphical abstractThe improvement of classification accuracy obtained after the application of Bayesian approach to the optimization of Support Vector Machines parameters. PMID- 26273326 TI - Erratum: Neuroendocrine and metabolic components of dopamine agonist amelioration of metabolic syndrome in SHR rats. AB - [This corrects the article DOI: 10.1186/1758-5996-6-104.]. PMID- 26273324 TI - Mechanistic insights revealed by lipid profiling in monogenic insulin resistance syndromes. AB - BACKGROUND: Evidence from several recent metabolomic studies suggests that increased concentrations of triacylglycerols with shorter (14-16 carbon atoms), saturated fatty acids are associated with insulin resistance and the risk of type 2 diabetes. Although causality cannot be inferred from association studies, patients in whom the primary cause of insulin resistance can be genetically defined offer unique opportunities to address this challenge. METHODS: We compared metabolite profiles in patients with congenital lipodystrophy or loss-of function insulin resistance (INSR gene) mutations with healthy controls. RESULTS: The absence of significant differences in triacylglycerol species in the INSR group suggest that changes previously observed in epidemiological studies are not purely a consequence of insulin resistance. The presence of triacylglycerols with lower carbon numbers and high saturation in patients with lipodystrophy suggests that these metabolite changes may be associated with primary adipose tissue dysfunction. The observed pattern of triacylglycerol species is indicative of increased de novo lipogenesis in the liver. To test this we investigated the distribution of these triacylglycerols in lipoprotein fractions using size exclusion chromatography prior to mass spectrometry. This associated these triacylglycerols with very low-density lipoprotein particles, and hence release of triacylglycerols into the blood from the liver. To test further the hepatic origin of these triacylglycerols we induced de novo lipogenesis in the mouse, comparing ob/ob and wild-type mice on a chow or high fat diet, confirming that de novo lipogenesis induced an increase in relatively shorter, more saturated fatty acids. CONCLUSIONS: Overall, these studies highlight hepatic de novo lipogenesis in the pathogenesis of metabolic dyslipidaemia in states where energy intake exceeds the capacity of adipose tissue. PMID- 26273327 TI - The new open era for Thoracic Cancer. PMID- 26273328 TI - Roles of miR-182 in sensory organ development and cancer. AB - Micro ribonucleic acids (miRNAs) are a cluster of small non-coding RNA molecules predicted to regulate more than 30% of coding messenger (m)RNAs in the human genome and proven to be essential in developmental and pathological processes. The miR-182 gene was first found to be abundantly expressed in sensory organs and regulates the development of the retina and inner ear. Further studies revealed its roles in osteogenesis and T cell differentiation. In addition, the involvement of miR-182 in cancer initiation and progression has recently been uncovered by a growing body of evidence, the majority of which supports its promoting effects in cell proliferation, angiogenesis, and invasion, as well as distant metastasis of various cancer types. Clinical analyses demonstrated the link of miR-182 expression to poor prognosis in cancer patients. Mechanistically, multiple downstream genes including missing-in-metastasis, microphthalm associated transcription factor, FoxO1, cylindromatiosis, and others, can be targeted by miR-182 and mediate its roles in cancer. miR-182 is also interconnected with prominent cancer-related signaling pathways, such as transforming growth factor beta and nuclear factor kappa beta. Interestingly, it was shown that in vivo targeting of miR-182 prevented liver metastasis of melanoma. miR-182 is emerging as an important regulator of malignancies, which warrants further study to establish the application potential of miR-182 in cancer diagnosis and treatment. PMID- 26273329 TI - Medical management of lung cancer: Experience in China. AB - Lung cancer is the leading cause of death from cancer worldwide, as well as in China. A multidisciplinary treatment strategy for lung cancer, which includes medical and radiation oncology, surgery, and pathology is used in clinical practice in China. Chinese lung cancer patients are treated according to different pathologic and genetic types of the disease. For those with active epidermal growth factor receptor (EGFR) mutation, EGFR tyrosine kinase inhibitors (EGFR-TKIs) are used in first-, second- or third-line and maintenance treatment of non-small cell lung cancer (NSCLC). For patients with anaplastic lymphoma kinase (ALK) gene rearrangement, Crizotinib is a promising treatment in advanced NSCLC patients. A platinum-based regimen remains the mainstay of first-line systemic therapy for advanced NSCLC patients who are negative for EGFR mutation or ALK gene rearrangement. For patients with non-squamous NSCLC, Pemetrexed plus Cisplatin is recommended in first-line systemic therapy. An Endostatin combination with chemotherapy is used in first- and second-line advanced NSCLC patients. S-1 presents a new option of chemotherapy in advanced NSCLC cases. Cisplatin-based doublet chemotherapy is commonly used in NSCLC patients after surgery as adjuvant therapy. EGFR-TKIs are now being assessed in the adjuvant setting. The standard first-line chemotherapy regimen of small cell lung cancer (SCLC) is platinum with Etoposide (PE). Amrubicin provides similar survival compared with the PE regimen with an acceptable toxicity profile in extensive stage SCLC patients. Supportive care, such as traditional Chinese medicine and pegylated filgrastim, play an important role in improving patients' quality of life. PMID- 26273331 TI - Clinical characteristics of the mixed form of neuroendocrine tumor in the lung: A retrospective study in 2501 lung cancer cases. AB - BACKGROUND: A neuroendocrine tumor (NET) is a special kind of epithelial tumor with predominant neuroendocrine differentiation, which arises throughout the body, including the lung. A subpopulation of lung cancer patients suffer from the mixed (combined) form of NET with components of non-neuroendocrine carcinoma. However, the clinical characteristics of the mixed form of NET are not well established. METHODS: We analyzed 2501 consecutive cases of primary lung cancer from 2009 to 2011. The diagnosis, histology, therapy, and outcome were collected. RESULTS: A total of 22 patients were enrolled. The occurrence rate of lung cancer was 0.9%. Neither gender (1.2% and 0.3% for male and female, respectively, P = 0.35) nor age (0.6% and 1.3% for patients aged <=60 and >60, respectively, P = 0.13) was associated with the onset of this disease; however it has become more frequent in recent years (0.6% and 1.6% at the time <= and >2010 respectively, P = 0.03). This cohort of 22 patients had a median survival of 60.0 months (95% confidence interval: 14.3-105.6 months). Patients with metastatic disease (60 months and not reached [NR], P = 0.18) or a small-cell lung cancer component tended to have a shorter survival (35 months and NR, P = 0.16). Patients who underwent surgery had a significantly longer survival period (NR and 17.0 months, P = 0.001). CONCLUSIONS: A mixed form of NET in the lung is a rare disease. While stage and histology might influence prognosis, surgery is the critical factor for long-term survival. PMID- 26273330 TI - Review of aerobic glycolysis and its key enzymes - new targets for lung cancer therapy. AB - Most tumor cells show different metabolic pathways than normal cells. Even under the conditions of sufficient oxygen, they produce energy by a high rate of glycolysis followed by lactic acid fermentation in the cytosol, which is known as aerobic glycolysis or the Warburg effect. Lung cancer is a malignant tumor with one of the highest incidence and mortality rates in the world at present. However, the exact mechanisms underlying lung cancer development remain unclear. The three key enzymes of glycolysis are hexokinase, phosphofructokinase, and pyruvate kinase. Lactate dehydrogenase catalyzes the transfer of pyruvate to lactate. All four enzymes have been reported to be overexpressed in tumors, including lung cancer, and can be regulated by many oncoproteins to promote tumor proliferation, migration, and metastasis with dependence or independence of glycolysis. The discovery of aerobic glycolysis in the 1920s has provided new means and potential therapeutic targets for lung cancer. PMID- 26273332 TI - Silencing of tripartite motif (TRIM) 29 inhibits proliferation and invasion and increases chemosensitivity to cisplatin in human lung squamous cancer NCI-H520 cells. AB - BACKGROUND: TRIM29 belongs to the tripartite motif (TRIM) protein family. It has been reported to be a tumor suppressor or have oncogenic function in many cancer types. The aim of this study was to investigate whether downregulation of TRIM29 by small interfering ribonucleic acid (siRNA) could inhibit cell proliferation and invasion and increase chemosensitivity to cisplatin in human lung squamous cancer NCI-H520 cells in vitro. METHODS: We transformed TRIM29 siRNA into NCI H520 cells. Real time reverse transcriptase polymerase chain reaction and Western blotting assay were employed to determine TRIM29 messenger (m)RNA and protein expressions. MTT assay was used to determine the cell proliferation. Transwell invasion assay was used to determine the cell invasion. An Annexin V-propidium iodide (AnnV/PI) staining apoptosis test was used for detecting apoptosis. RESULTS: TRIM29 siRNA could specifically and efficiently suppress TRIM29 expression at both mRNA and protein levels. Silencing of the TRIM29 by siRNA in NCI-H520 cells inhibited cell proliferation and invasion in vitro. TRIM29 knockdown resulted in chemosensitivity enhancement in NCI-H520 cells. CONCLUSION: Downregulation of TRIM29 can lead to potent antitumor activity and chemosensitizing effect in human lung squamous cancer NCI-H520 cells. PMID- 26273333 TI - Prognostic factors in patients with postoperative brain recurrence from completely resected non-small cell lung cancer. AB - BACKGROUND: Treatment strategies for brain metastasis from lung cancer have been making progress. The aim of this retrospective analysis was to investigate the post-recurrent prognostic factors in patients with brain metastasis after complete resection of non-small cell lung cancer (NSCLC). METHODS: We retrospectively reviewed the medical records of 40 patients found to have postoperative brain metastasis from NSCLC in our institution from 2002 to 2008. All patients had undergone radical pulmonary resection for the lung cancer. The impact of numerous variables on survival were assessed, including gender, age, carcinoembryonic antigen (CEA), tumor size, N status, histological type, number of brain metastases, tumor size of brain metastasis, presence of symptoms from the brain tumor(s), and use of perioperative chemotherapy. RESULTS: The median follow-up was 20.6 months (range, 3.4-66 months). The five-year survival rate from the diagnosis of brain recurrence was 22.5%. In univariate analysis, the favorable prognostic factors after brain recurrence included a normal range of CEA, no extracranial metastasis, no symptoms from the brain metastasis, brain metastasis (less than 2 cm), and radical treatment (craniotomy or stereotactic radiosurgery [SRS]). The multivariate Cox model identified that a small brain metastasis and radical treatment were independent favorable prognostic factors. CONCLUSIONS: This study found that the implementation of radical therapy for metastatic brain tumor(s) when the tumor is still small contributed to an increase in patients' life expectancy. PMID- 26273334 TI - Pharmacokinetic profile of paclitaxel in the plasma, lung, and diaphragm following intravenous or intrapleural administration in rats. AB - BACKGROUND: The optimal chemotherapy route for non-small cell lung cancers involving the phrenic nerve and diaphragm is unclear. The pharmacokinetic properties of paclitaxel following intravenous (IV) or intrapleural (IP) administration were analyzed in the plasma, lung, and diaphragm in a rat model. The purpose of this study was to determine whether IP injection increased paclitaxel concentration in the diaphragm. METHODS: Paclitaxel was administered by IV or IP to male Sprague-Dawley rats. The concentration of drug in the plasma, lung, and diaphragm was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters area under the curve (AUC), mean residence time (MRT), peak plasma concentration (Cmax), and half-life (t1/2) were analyzed. RESULTS: Paclitaxel concentration in the plasma, lung, and diaphragm decreased quickly following IV administration. However, after IP injection, paclitaxel reached a high concentration in the plasma, lung, and diaphragm that declined gradually. Significant differences in all parameters, except Cmax in the lung, were observed between the two routes of administration (all P < 0.05). Plasma exposure to paclitaxel IP was 41.1% of that observed after IV in the first 24 hours (P < 0.05). IP also significantly increased exposure of paclitaxel in comparison with IV administration to 267.3% and 905.7% of IV administration in the lung and diaphragm, respectively (P < 0.05). CONCLUSION: These results suggest that IP administration may reduce systemic distribution of paclitaxel and increase the concentration in the lung and diaphragm. This could increase therapeutic efficacy by increasing the available drug and reduce systemic toxicity. PMID- 26273335 TI - Predictive factors for acute radiation pneumonitis in postoperative intensity modulated radiation therapy and volumetric modulated arc therapy of esophageal cancer. AB - BACKGROUND: Radiation pneumonitis (RP) is a common side reaction in radiotherapy for esophageal cancer. There are few reports about RP in esophageal cancer patients receiving postoperative intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). This study aims to analyze clinical or dosimetric factors associated with RP, and provides data for radiotherapy planning. METHODS: We reviewed 68 postoperative esophageal cancer patients who were treated with radiotherapy at the West China Hospital from October 2010 to November 2012 to identify any correlation between the clinical or dosimetric parameters and acute radiation pneumonitis (ARP) or severe acute radiation pneumonitis (SARP) by t-test, chi-square test, and logistic regression analysis. RESULTS: Of the 68 patients, 33 patients (48.5%) developed ARP, 13 of which (19.1%) developed SARP. Of these 33 patients, 8 (11.8%), 12 (17.6%), 11 (16.2%), and 2 (2.9%) patients were grade 1, 2, 3, and 4 ARP, respectively. Univariate analysis showed that lung infection during radiotherapy, use of VMAT, mean lung dose (MLD), and dosimetric parameters (e.g. V20, V30) are significantly correlated with RP. Multivariate analysis found that lung infection during radiotherapy, MLD >= 12 Gy, and V30 >= 13% are significantly correlated with an increased risk of RP. CONCLUSION: Lung infection during radiotherapy and low radiation dose volume distribution were predictive factors associated with RP and should be accounted for during radiation planning. PMID- 26273336 TI - Establishment and management of a lung cancer biobank in Eastern China. AB - BACKGROUND: The prevalence of lung cancer, a highly complex neoplasm, increases annually. Thus, a lung cancer biobank, which stores lung cancer tissue and blood matched according to standard methods, is needed to advance lung cancer research and develop promising therapies. METHODS: To accomplish this aim, we implemented standardized procedures for tissue samples and patient information acquired from consenting donors. The banked tissue includes blood, pleural effusions, and surgical resection samples. An independent information management system was used to match samples and collect data, including clinical cancer manifestation, laboratory tests, and de-identified data about cancer patients. RESULTS: From 2009 to 2013, more than 2000 lung cancer cases were collected. At this time, we have more than 10 000 biological samples stored in our biobank. DNA, ribonucleic acid (RNA), and protein quality were confirmed to be appropriate for clinical and basic research. CONCLUSION: Our standardized, large-scale lung cancer biobank offers high quality cancer research samples for China and the world. PMID- 26273337 TI - Evaluation of hormone receptor, human epidermal growth factor receptor-2 and Ki 67 with core needle biopsy and neoadjuvant chemotherapy effects in breast cancer patients. AB - BACKGROUND: We investigated the reliability of core needle biopsy (CNB) in evaluating the status of hormone receptor (HR), human epidermal growth factor receptor (HER)-2, and Ki-67 status, and the effect of neoadjuvant chemotherapy (NAC) on the expression of these immunohistochemical markers. METHODS: Among 177 patients with breast adenocarcinoma, 95 patients underwent NAC and the remaining 82 patients made up the control group. Immunohistochemistry (IHC) was used to evaluate the expression status of estrogen receptor (ER), progesterone receptor (PR), HER-2, and Ki-67 in the specimens obtained by surgical excision or CNB. RESULTS: In the control group, the expression of ER, PR, HER-2, and Ki-67 was highly consistent between samples from surgical excision or CNB (all r > 0.8, P < 0.05). In the NAC group, the proportions of samples with changes in ER, PR, HER 2, and Ki-67 expression were 12.7%, 24.1%, 5.1%, and 38.0%, respectively; the figures in the control group were 2.4%, 4.9%, 2.4%, and 7.3%, respectively, which significantly differed in ER, PR, and Ki-67 (P < 0.05), but not HER-2 (P > 0.05). In the NAC group, pre- and post-treatment ER(+) rates did not significantly differ (P > 0.05), although PR(+) and high Ki-67 expression rates did significantly differ (P < 0.05). CONCLUSION: Neither CNB nor surgical excision samples gave highly consistent results in HR, HER-2, and Ki-67 status. NAC can alter HR and Ki-67 status in breast adenocarcinoma patients. NAC decreased PR(+) rate and Ki-67 expression. The mean ER(+) rate exhibited a decreasing, but insignificant trend after NAC treatment. NAC had no significant effect on HER-2 expression. PMID- 26273338 TI - Analysis for the mechanism between the small cell lung cancer and non-small cell lung cancer combing the miRNA and mRNA expression profiles. AB - BACKGROUND: We investigated the relationship between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) based on micro ribonucleic acid (miRNA) and messenger (m)RNA expression profiles. METHODS: Utilizing the differentially expressed mRNAs and the targeting miRNAs, the mRNA-miRNA network for the two cancers was constructed. By integrating the miRNA expression profile, drug, and drug targets, miRNA-drug target-drug networks were established and the mechanisms in drug therapy efficacy were compared between SCLC and NSCLC. RESULTS: Drug targets of different expressed miRNAs of SCLC are mainly located in the organelle, act in the electron carrier activity, and consist of the synapse; while drug targets of NSCLC are the membrane-enclosed lumen, mainly distributed in the extracellular region and synapse, and function in the binding. Drug targets of miRNA expressed commonly in the two cancers are involved in the reproduction multi-organism process. In SCLC, the miR-16 in the miRNA-drug target drug network is significant and follows the result of the mRNA-miRNA network. The pigmentation and rhythmic process of SCLC is different from NSCLC, while the process of cellular component biogenesis and cellular component organization are important for the occurrence of NSCLC. miR-16 in the miRNA-mRNA-drug network of SCLC is significant and we acquired 11 potential drugs, such as dexamethasone and budesonide. The miR-124 for NSCLC is important in the network and 17 potential drugs were screened, including dexamethasone and budesonide. CONCLUSIONS: These findings suggest that miR-16 and miR-124 might be novel diagnostic and prognostics markers for SCLC and NSCLC, respectively. PMID- 26273339 TI - Expression of interleukin-12 by adipose-derived mesenchymal stem cells for treatment of lung adenocarcinoma. AB - BACKGROUND: Studies have revealed mesenchymal cells tend to directionally migrate toward tumor cells and inhibit tumor growth. However, there have been rare reports about adipose-derived mesenchymal stem cells (AMSCs), which achieved stable expression of interleukin (IL)-12 to inhibit lung adenocarcinoma cell migration and invasion. We aimed to achieve stable expression of IL-12 in AMSCs through transgenic technology and utilize the paracrine effect of IL-12 to inhibit lung adenocarcinoma cell migration and invasion. METHODS: Adipose-derived AMSCs were transduced with lentivirus encoding IL-12. IL-12/AMSCs and lung adenocarcinoma A549 cells were co-cultured using a cylinder column to assess cellular attraction, and expression of Ki67 was detected. Dual-chamber transwell experiments were used to assess migration and invasiveness of A549 cells exposed to conditioned media from IL-12/AMSCs. RESULTS: When A549 cells were co-cultured with lentivirus vectors (LV)-IL-12-green fluorescent protein (GFP)/AMSCs, the intercellular distance was great (346.44 +/- 41.07 MUm vs. 201.58 +/- 27.96 MUm vs. 191.45 +/- 24.07 MUm) (F = 25.414, P < 0.05); the Ki67-positive rate was low (59.13 +/- 17.21% vs. 92.31 +/- 6.11% vs. 94.25 +/- 5.27%) (F = 21.426, P < 0.05). When the lower Transwell chamber contained culture medium from LV-IL-12 GFP/AMSCs, the percentage of the invasive A549 cells was low (31.55 +/- 6.21% vs. 70.65 +/- 10.46% vs. 68.65 +/- 9.50%) (F = 27.494, P < 0.05). The percentages of colonized A549 cells that invaded the culture media of LV-IL-12-GFP/AMSCs were low (4.46 +/- 1.21 vs. 10.11 +/- 2.07 vs. 9.48 +/- 1.4) (F = 23.219, P < 0.05). CONCLUSIONS: AMSCs could target lung carcinoma and mediate stable expression of IL-12, to play a role in tumor treatment. PMID- 26273340 TI - Clinicopathologic characteristics, treatment outcomes, and prognostic factors of primary thoracic soft tissue sarcoma: A multicenter study of the Anatolian Society of Medical Oncology (ASMO). AB - BACKGROUND: Soft tissue sarcomas (STSs) are rare malignant tumors of embryogenic mesoderm origin. Primary thoracic STSs account for a small percentage of all STSs and limited published information is available. This study aimed to identify the prognostic factors for thoracic STSs and evaluate the disease's clinical outcomes. METHODS: The medical records of 109 patients with thoracic STSs who were treated between 2003 and 2013 were retrospectively reviewed. Patients' survival rates were analyzed and potential prognostic factors evaluated. RESULTS: The median follow-up period was 29 months (range: 1-121 months). STSs were most frequently localized on the chest wall (n = 42; 38.5%) and lungs (n = 42; 38.5%). The most common histological types were malignant fibrous histiocytoma (n = 23; 21.1%), liposarcoma (n = 17; 15.6%), and leiomyosarcoma (n = 16; 14.7%). The median survival time of all patients was 40.3 months (95% confidence interval, 14.22-66.37 months), with one and five-year survival rates of 93.4% and 63.5%, respectively. Univariate analysis of all groups revealed that metastatic stage, unresectability, tumor diameter of >10 cm, tumor location other than the chest wall, and grade 3 diseases were predictable of poor survival. However, only grade 3 diseases and tumor location other than the chest wall were confirmed by multivariate analysis as poor prognostic factors. CONCLUSIONS: Primary thoracic STSs are rarely seen malignant tumors. Our results indicated that patients with low-grade tumors and those localized on the chest wall often experienced better survival outcomes. PMID- 26273341 TI - Mouse double minute-2 homolog (MDM2)-rs2279744 polymorphism associated with lung cancer risk in a Northeastern Chinese population. AB - BACKGROUND: Altered expression or function of mouse double minute-2 (MDM2) protein could contribute to lung carcinogenesis; thus, this study investigated MDM2-rs2279744 polymorphism together with other epidemiologic factors for their association with lung cancer risk. METHODS: A total of 500 lung cancer patients and 500 age and gender-matched healthy controls living in Northeastern China were recruited for genotyping of MDM2-rs2279744. Clinicopathological data was collected and subjected to univariate and multivariate analyses. RESULTS: In univariate analysis, the MDM2-rs2279744 G/G genotype versus T/T + T/G genotypes showed a tendency toward a higher incidence of lung cancer in the recessive model (P = 0.043). However, there were no significant differences when it was analyzed by the dominant, additive, or multiplicative models. A significantly increased lung cancer risk was observed associated with lower education level, lower body mass index, cancer family history, prior diagnosis of chronic obstructive pulmonary disease and pneumonia, exposure to pesticide or gasoline/diesel, tobacco smoking, and heavy cooking emissions when assessed by multivariate analyses. Moreover, MDM2-rs2279744 was still a significant risk factor even after incorporating environmental and lifestyle factors. However, there was no association between MDM2-rs2279744 and other factors. CONCLUSIONS: The MDM2 rs2279744 G/G genotype was associated with a higher lung cancer risk, even after incorporating other epidemiologic factors. PMID- 26273342 TI - Solitary pulmonary metastasis from malignant melanoma of the bulbar conjunctiva presenting as a pulmonary ground glass nodule: Report of a case. AB - We herein report a case of solitary pulmonary metastasis from malignant melanoma that presented as a pulmonary ground glass nodule. A 57-year-old man who had undergone resection of a malignant melanoma of the right bulbar conjunctiva at the age of 51 was referred to our hospital for management of ground glass opacity in his left lung. Because radiological examination suggested the nodule was an adenocarcinoma in situ, computed tomography (CT) follow-up was planned. CT examination performed nine months later showed that the nodule had grown from 6 mm to 8 mm. Moreover, CT performed one and a half years after first detection revealed that the nodule had grown up to 10 mm. The patient, therefore, underwent partial resection of the lung for diagnosis and treatment. Pathological examination of the resected specimen revealed atypical cells with melanin granules proliferating in a lepidic-like fashion. The cells were positive on S 100 staining, indicating a pulmonary metastasis from malignant melanoma. Thus, metastatic tumors from malignant melanoma can present as ground glass opacities. PMID- 26273343 TI - Intrathymic ectopic parathyroid adenoma caused primary hyperparathyroidism with vitamin D deficiency several years after bariatric surgery. AB - Up to 25% of patients with primary hyperparathyroidism have ectopic parathyroid adenoma. A 45-year-old formerly obese woman underwent extended thymectomy for a parathyroid adenoma located in hyperplastic thymic tissue, associated with primary hyperparathyroidism and severe vitamin D deficiency, but normal bone mineral density. At nine months follow-up, all laboratory test results were within normal limits and she presented no symptoms and no recurrence of disease. In this case, autonomous growth of a parathyroid adenoma was reasonably secondary to chronic calcium and vitamin D malabsorption, which often occurs after bariatric surgery for pathologic obesity. PMID- 26273344 TI - Granulocyte-colony stimulating factor (G-CSF) producing malignant pleural mesothelioma: Report of a case. AB - This report presents a case of malignant pleural mesothelioma (MPM) producing granulocyte colony-stimulating factor (G-CSF) that was treated by tumor resection. A 76-year-old male presented with a huge right-side chest wall tumor, along with a slight fever and chest wall pain. Laboratory findings showed an increased white blood cell count (64600 cells/MUL) and C-reactive protein level (20.57 mg/dL). The patient underwent surgical removal of the tumor along with tissue from the chest wall and histopathological analysis led to a diagnosis of sarcomatous type of MPM. Immunohistochemical findings for both anti-human G-CSF and interleukin-6 monoclonal antibodies were positive. Although the general condition of the patient quickly improved after surgery, local recurrence occurred two months later and he died of respiratory failure seven months after the operation, though surgery provided symptom relief. G-CSF-producing MPMs usually show a poor prognosis, though less-invasive surgery may be considered for relief of symptoms. PMID- 26273345 TI - Bilateral spontaneous pneumothorax and massive pneumomediastinum under Pazopanib therapy. PMID- 26273346 TI - Chinese expert consensus workshop report: Guidelines for thermal ablation of primary and metastatic lung tumors. AB - Although surgical resection is the primary means of curing both primary and metastatic lung cancers, about 80% of lung cancers cannot be removed by surgery. As most patients with unresectable lung cancer receive only limited benefits from traditional radiotherapy and chemotherapy, many new local treatment methods have emerged, including local ablation therapy. The Minimally Invasive and Comprehensive Treatment of Lung Cancer Branch, Professional Committee of Minimally Invasive Treatment of Cancer of the Chinese Anti-Cancer Association has organized multidisciplinary experts to develop guidelines for this treatment modality. These guidelines aim at standardizing thermal ablation procedures and criteria for selecting treatment candidates and assessing outcomes; and for preventing and managing post-ablation complications. PMID- 26273348 TI - Magnetic resonance imaging for N staging in non-small cell lung cancer: A systematic review and meta-analysis. AB - BACKGROUND: Lymph node staging in non-small cell lung cancer (NSCLC) is essential for deciding appropriate treatment. This study systematically reviews the literature regarding the diagnostic performance of magnetic resonance imaging (MRI) in lymph node staging of patients with NSCLC, and determines its pooled sensitivity and specificity. METHODS: PubMed and Embase databases and the Cochrane library were used to search for relevant studies. Two reviewers independently identified the methodological quality of each study. A meta analysis of the reported sensitivity and specificity of each study was performed. RESULTS: Nine studies were included. These studies had moderate to good methodological quality. Pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-) and diagnosis odds ratio (DOR) for per-patient based analyses (7 studies) were 74%, 90%, 7.5, 0.26, and 36.7, respectively, and those for per-lymph node based analyses (5 studies) were 77%, 98%, 42.24, 0.21, and 212.35, respectively. For meta-analyses of quantitative short time inversion recovery imaging (STIR) and diffusion-weighted imaging (DWI), pooled sensitivity and specificity were 84% and 91%, and 69% and 93%, respectively. Pooled LR+ and pooled LR- were 8.44 and 0.18, and 8.36 and 0.36, respectively. The DOR was 56.29 and 27.2 respectively. CONCLUSION: MRI showed high specificity in the lymph node staging of NSCLC. Quantitative STIR has greater DOR than quantitative DWI. Large, direct, and prospective studies are needed to compare the diagnostic power of STIR versus DWI; consistent diagnostic criteria should be established. PMID- 26273349 TI - Pazopanib diminishes non-small cell lung cancer (NSCLC) growth and metastases in vivo. AB - BACKGROUND: Anti-angiogenesis has been demonstrated to have a critical role in lung cancer pathogenesis. Here, we characterized the effect of the small-molecule angiogenesis inhibitor pazopanib on non-small cell lung cancer (NSCLC) cells. METHODS: NSCLC cells were tested for viability and migration after incubation with varying concentrations of pazopanib. Further, the phosphorylation status of extracellular signal-regulated kinase, protein kinase B, and MEK were assessed in vitro. For in vivo testing, mice grafted with NSCLC cell lines L9981 and A549 were treated orally with pazopanib. RESULTS: Pazopanib inhibits signaling pathways in tumor cells, thus blocking NSCLC cell growth and migration in vitro and inducing tumor cell arrest at G0/G1 phase. We show that pazopanib could inhibit tumor cell growth, decrease metastases, and prolong survival in two mouse xenograft models of human NSCLC. CONCLUSION: These preclinical studies of pazopanib show the possibility of clinical application and, ultimately, improvement in patient outcome. PMID- 26273350 TI - Surgical results of resectable small cell lung cancer. AB - BACKGROUND: The standard of care for patients with small cell lung cancer (SCLC) is chemotherapy and radiotherapy, even for patients with limited disease. To define the role of surgical resection in patients with limited SCLC, we investigated the outcomes of patients diagnosed with limited-stage disease (LD) SCLC. METHODS: The records of 57 LD SCLC patients who underwent surgical resection from April 1974 to March 2012 were retrospectively analyzed. RESULTS: There were six women and 51 men, with a median age of 63.5 years. The overall five-year survival rate was 28.6% (median, 18.2 months). The p-stage II and III patients had a significantly worse survival than the p-stage I patients (13.4% vs. 43.4%, P = 0.0036). However, the c-stage was not found to correlate with survival. Patients who underwent pneumonectomy had a significantly worse outcome than those who underwent other surgical procedures (0.0% vs. 32.0%, P = 0.0002). In a multivariate Cox proportional hazards analysis, p-stage II or III (hazard ratio [HR] 3.040 P = 0.0017) and pneumonectomy (HR 6.177, P = 0.00159) were significant independent predictors of an adverse survival outcome. CONCLUSIONS: Surgical treatment can be considered in SCLC patients with pathologically proven N0 status, although pneumonectomy should be avoided. PMID- 26273351 TI - Clinical study on postoperative recurrence in patients with pN1 esophageal squamous cell carcinoma. AB - BACKGROUND: The 7th edition Union for International Cancer Control esophageal cancer staging system has changed the pathological N stage from N0, N1 (the existence state of regional lymph node metastasis) to N0, N1, N2, and N3 (number of regional lymph node metastasis). This study was designed to analyze the influencing factors of early recurrence in patients with pathological N1 stage (pN1 stage) esophageal squamous cell carcinoma (ESCC) after radical esophagectomy. METHOD: A retrospective study of 95 consecutive pN1 stage ESCC patients was conducted. The Cox proportional hazards model was used to determine the independent risk factors for recurrence. RESULTS: Recurrence was recognized in 52 patients (54.7%) within three years after surgery. The median time to tumor recurrence was 14.2 months. Locoregional recurrence was found in 42 patients (44.2%) and hematogenous metastasis in 10 patients (10.5%). Recurrence closely correlated with pT stage, positive lymph node metastasis (LNM) in 2-station and/or 2-field, pathologic stage, intramural metastasis, lymph-vascular invasion, and postoperative adjuvant chemotherapy (chi(2) = 8.853~65.695, P < 0.05). Cox multivariate analysis showed that pT3-4a stage (odds ratio [OR] = 3.604, P = 0.027), positive LNM in 2-station (OR = 4.834, P = 0.009) or 2-field (OR = 5.689, P = 0.003) and no adjuvant chemotherapy (OR = 1.594, p = 0.048) were independent risk factors for postoperative recurrence. CONCLUSION: Adjuvant chemotherapy might be helpful to reduce the recurrence rate of pN1 patients with thoracic ESCC. Induction therapy could further improve the therapeutic effect of pN1 ESCC with suspected multi-station and/or multi-field LNM. PMID- 26273352 TI - Transthoracic biopsy of lung masses: Non technical factors affecting complication occurrence. AB - BACKGROUND: To investigate the transthoracic computed tomography (CT)-guided lung nodule biopsy complications and risk factors associated with the development of these complications. METHODS: We retrospectively evaluated a total of 41 CT guided transthoracic biopsy complications. Data was analyzed by chi-square and independent sample t-tests. RESULTS: Twenty-seven patients (28.7%) developed pneumothorax and eight patients (8.5%) developed parenchymal hemorrhage, and four patients (4.3%) hemothorax and two (2.1%) patients developed subcutaneous emphysema. A significant correlation was obtained between the development of pneumothorax and lesion size (P = 0.040), and the distance that traversed the parenchyma (P = 0.001). There was a statistically significant difference between the parenchymal hemorrhage and lesion size and the distance from passed parenchyma (P values were 0.021 and 0.008, respectively). An increased incidence of parenchymal hemorrhage and pneumothorax was observed at small size and deep seated lesions. CONCLUSION: Lesion size and the distance that traversed the parenchyma on the biopsy tract are the most important factors that influence the development of complications in CT-guided transthoracic biopsy. PMID- 26273353 TI - Multiple primary cancers involving lung cancer at a single tertiary hospital: Clinical features and prognosis. AB - BACKGROUND: The development of other primary cancers in patients with lung cancer is unfortunate and uncommon, although the frequency is increasing. The aim of this study was to determine the clinical features and prognosis in patients with multiple primary cancers (MPC) involving lung cancer. METHODS: After a retrospective review of 1644 patients who were newly diagnosed with primary lung cancer between 1998 and August 2012 at a tertiary hospital, 105 patients were included. RESULTS: The median age at the time of lung cancer diagnosis was 67 years, and 68 patients were male. Synchronous primary cancers occurred in 47% of the study population (49/105). Among those with metachronous cancer (56/105), the median interval between the diagnosis of lung cancer and another malignancy was 47.1 months; 21 patients were diagnosed with lung cancer as the first primary tumor. The most frequent type of other malignancy was urogenital (30%), followed by gastrointestinal (30%) and thyroid malignancies (16%). Advanced stage of lung cancer (hazard ratio (HR), 3.2; 95% confidence interval (CI), 1.8-5.7; P < 0.001), supportive care only as treatment for lung cancer (HR, 2.8; 95% CI, 1.3 6.0; P = 0.006), and head and neck cancer as another malignancy (HR, 3.9; 95% CI, 1.4-10.8; P = 0.010) were independent predictors of shorter survival from the time of diagnosis of the second primary cancer. CONCLUSION: Advanced lung cancer stage, symptomatic supportive care only without antitumor therapy for lung cancer, and head and neck cancer as another primary malignancy were poor prognostic factors in patients with MPC involving primary lung cancer. PMID- 26273354 TI - Risk factors for recurrence after complete resection of pathological stage N2 non small cell lung cancer. AB - BACKGROUND: Tumor recurrence is the most common cause of treatment failure, especially after complete resection of pathological stage N2 non-small cell lung cancer (NSCLC). In this study, we investigated the clinicopathological characteristics in order to identify independent risk factors for postoperative recurrence. METHODS: Between January 2001 and December 2013, 96 patients who underwent surgical resection for pathological N2 NSCLC were retrospectively reviewed. Recurrence-free survival (RFS) was calculated by the Kaplan-Meier method to explore risk factors, while the Cox proportional hazard model was used to assess independent predictors. RESULTS: The median and five-year RFS rates were 15 months and 27.4%, respectively. Univariate analysis showed a significantly poorer prognosis for non-regional N2 metastasis, more than three metastatic N2 lymph nodes, multiple N2 station, and multiple N2 zone involvement. Multivariate analysis demonstrated that non-regional N2 metastasis (hazard ratio [HR] 1.857, 95% confidence interval [CI] 1.061-3.249, P = 0.030) and more than three metastatic N2 lymph nodes (HR 2.555, 95% CI 1.164-5.606, P = 0.019) were independent risk factors for RFS. Additionally, the incidence of non-regional N2 metastasis was higher in patients with a primary tumor in the left lower (57.1%) or right lower lobe (48.1%), followed by left upper (31.8%), right middle (14.3%) and right upper lobe (7.7%). CONCLUSION: The combination of the distribution and number of metastatic N2 lymph nodes provides a more accurate prediction for N2 NSCLC regarding recurrence. Non-regional N2 metastasis could occur with a primary tumor in any lobe, but occurs more frequently in the lower lobe. PMID- 26273355 TI - In vitro study of the effect of small interfering ribonucleic acid on the expression of FOXN1 and B cell-attracting chemokine 1 in thymoma cell lines. AB - BACKGROUND: To determine the relationship between FOXN1 (a transcription factor) and B cell-attracting chemokine 1 (BCA1, a chemotactic factor), and their influence on thymoma cell proliferation. METHODS: We initially used immunohistochemical methods to compare the expression levels of FOXN1 and BCA1 in thymoma and non-thymomatous tissue samples. Reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were used to compare the expression of FOXN1 and BCA1 in thymoma cells (Thy0517) and normal thymic epithelial cells (CRL7660). We used ribonucleic acid interference (RNAi) to downregulate FOXN1 and BCA1 expression in Thy0517 cells to determine the relationship of the two factors with cell regulation. We also performed methyl thiazolyl tetrazolium (MTT) [3 (4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide] assays to detect the changes in Thy0517 cells after RNAi of FOXN1 and BCA1. RESULTS: FOXN1 and BCA1 expression levels were higher in thymoma tissues and Thy0517 cells compared to non-thymomatous tissue and CRL7660 cells (P < 0.05). RT-PCR and Western blot following RNAi showed that FOXN1 controlled BCA1 expression. MTT assay showed that FOXN1 and BCA1 downregulation rapidly inhibited Thy0517 cell proliferation. CONCLUSIONS: FOXN1 and BCA1 expression was higher in thymoma tissue samples and cell lines than in non-thymomatous tissue and normal thymic epithelial cells. FOXN1 acts upstream of BCA1 and both FOXN1 and BCA1 promote thymoma cell proliferation. PMID- 26273356 TI - Analysis of the coincidence rate between imaging and pathological findings of pulmonary metastasis in 45 cases with invasive bone and soft tissue sarcoma. AB - BACKGROUND: It is not uncommon for imaging examinations of invasive bone and soft tissue sarcoma patients during initial treatment or postoperative follow-up to detect pulmonary nodules. This has important significance in determining the nature of nodules either for tumor staging and therapeutic regimen selection or for prognosis evaluation. METHODS: A review was carried out of invasive bone and soft tissue sarcoma patients diagnosed and treated in the department of orthopedic oncology of Beijing Jishuitan Hospital from June 2002 to June 2012. Data from patients who developed pulmonary metastases, diagnosed by imaging and treated surgically, were analyzed for consistency between imaging and postoperative pathological diagnoses. RESULTS: A total of 45 patients with pulmonary metastasis diagnosed by imaging and treated with resection of pulmonary lesions were included in the study. Thirty-eight cases with pulmonary metastases (84.4%) and seven cases without pulmonary metastases (15.6%) were confirmed by postoperative pathological examination. The most common pathological type in the latter patients was tuberculosis, with a total of four cases (57.1%). CONCLUSION: There is a certain degree of misdiagnosis when using imaging for diagnosis of pulmonary metastasis, and attention should be paid to the pathological diagnosis of pulmonary metastasis in order to avoid overtreatment. Tuberculosis is most common in invasive bone and soft tissue sarcoma patients with pulmonary benign lesions, and it should be distinguished. PMID- 26273357 TI - Imaging characteristics of local recurrences after stereotactic body radiation therapy for stage I non-small cell lung cancer: Evaluation of mass-like fibrosis. AB - BACKGROUND: This study aimed to evaluate stereotactic body radiation therapy (SBRT) in patients with stage I non-small cell lung cancer (NSCLC) in terms of radiation-induced changes and computed tomography (CT) features of local recurrence by 18F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET). METHODS: From January 2006 to December 2012, 81 patients with NSCLC received SBRT. Follow-up consisted of non-contrast enhanced CT scans performed before and every four months after SBRT. In addition, 18F-FDG-PET/CT was conducted before SBRT for each patient, and one year later for each case suspected of recurrence. The CT findings were classified into two categories: mass-like fibrosis and others. The mass-like fibrosis category was subdivided into two patterns: mass-like consolidation (with air bronchogram) and mass-like opacity. RESULTS: Six patients had histologically confirmed local recurrence, including 83% (5/6) with mass-like opacity pattern and one case of modified conventional pattern (P = 0.02). In contrast, the non-recurrent group exhibited only 7% (5/75) with mass-like opacity and 13% (10/75) with mass-like consolidation pattern. Five patients with local recurrence presented with the mass-like opacity pattern, compared with 33% of patients (5/15) from the non recurrent group (P = 0.01) and showed an increase in maximum diameter at >=12 months after SBRT. The recurrent group also had a significantly higher standardized uptake value (SUVmax) than the non-recurrent group (P < 0.001), with all values >5 (range: 5.7-25.4). CONCLUSION: The following characteristics of mass-like fibrosis should be considered indicators of local recurrence after SBRT: opacity pattern, increasing maximum diameter, and SUVmax > 5. PMID- 26273358 TI - Establishment and characterization of a novel cell line derived from thymoma with myasthenia gravis patients. AB - BACKGROUND: Thymoma is a cancer with rare incidence, but it is a major malignancy in adult anterior mediastinum, occurring in about 40% of patients with myasthenia gravis. Because of the lack of thymic epithelial tumor cell lines, thymoma has lagged far behind other tumors in cytological studies. It is, therefore, quite necessary to establish a new thymic epithelial tumor cell line from Chinese patients to study the pathogenic mechanism and therapeutic methods. METHODS: Twenty-three samples of tumor tissues were collected from thymoma and thymic carcinoma patients for primary culture by tissue explant, suspension cell culture method, and collagenase digestion. We detected the biological characteristics and origin of the cell line after the establishment of a novel thymoma cell line. RESULTS: A novel cell line, designed as Thy0517, was established from thymoma type AB with myasthenia gravis patients by tissue explant. As an immortalized cell line, it always has a stable growth cycle, and there is no change in characteristics and morphology after culturing for 18 months and passing 160 generations in vitro. The experimental data demonstrate that the cell line exhibits the growth characteristics of tumor cells, the doubling time of 37 hours, with tumorigenicity in vitro and chromosome abnormality. Immunocytochemistry indicated that the cell line positive expression of CK7, CK8/18, CK19, CK-pan, CD24, BCL-2, P63, Vimentin, epithelial membrane antigen and epidermal growth factor receptor, lymphocyte related antigen CD99, and TdT were negatively expressed. CONCLUSIONS: The newly established thymic epithelial tumor cell line from Chinese patients provides a model in the study of thymoma and molecularly targeted therapies. PMID- 26273359 TI - Effects of histone deacetylase inhibitor trichostatin A combined with cisplatin on apoptosis of A549 cell line. AB - BACKGROUND: Histone deacetylase (HDAC) inhibitors combined with other drugs for the treatment of malignant tumors are used more and more widely. In this study, we investigated the effect of trichostatin A (TSA), a HDAC inhibitor, in combination with cisplatin, a cytotoxic chemotherapy agent, on the apoptosis of lung cancer A549 cells. METHODS: A549 cells were treated with TSA alone, cisplatin alone or the two drugs combined. Cell viability and apoptosis were evaluated using a light microscope, methyl thiazolyl tetrazolium (MTT) (3-[4, 5 dimethylthiazol-2-yl] -2, 5-diphenyltetrazolium bromide) assay and Hochst33258 staining. Moreover, Western blot analysis was employed to examine the alterations of apoptosis protein: cellular Fas-associated death domain-like interleukin-1 beta converting enzyme inhibitory protein (cFLIP) and caspase-8 in A549 cells in response to the different exogenous stimuli. RESULTS: Compared with single-agent treatment, the co-treatment of A549 cells with TSA and cisplatin synergistically inhibited cell proliferation, induced apoptosis, and increased the inhibition rate. Treatment with TSA and cisplatin led to a significant decrease of cFLIP expression. Furthermore, the treatment of A549 cells with TSA and cisplatin resulted in a significant decrease of pro-caspase-8 and a significant increase of caspase-8. CONCLUSIONS: Synergistic anti-tumor effects are observed between cisplatin and TSA in lung cancer cells. The combination of TSA with cisplatin may be a more effective method in human lung cancer treatment. PMID- 26273360 TI - Epidemiology of lung cancer in China. AB - BACKGROUND: Lung cancer is the most common cancer and the leading cause of cancer death in China. Along with socioeconomic development, environmental problems have intensified and the burden of lung cancer continues to increase. METHODS: In this study, national cancer registry data was used for evaluating incidence, mortality, time trend, and prediction. RESULTS: In China in 2010, 605 900 patients were diagnosed and 486 600 patients died of lung cancer. Throughout the last three decades, the mortality of lung cancer has dramatically increased, as shown in national death surveys. From 2000 to 2010, age specific incidence of lung cancer increased in most age groups. It is estimated that in 2015, the total number of new cases of lung cancer will reach 733 300. CONCLUSIONS: Lung cancer is a serious disease affecting public health and an effective control strategy is needed in China. PMID- 26273361 TI - Poor response to gefitinib in lung adenocarcinoma with concomitant epidermal growth factor receptor mutation and anaplastic lymphoma kinase rearrangement. AB - A patient presenting with concomitant epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation is rare. We report a non-small cell lung cancer (NSCLC) patient with concomitant ALK rearrangement and exon 19 (E746-A750del) EGFR mutation. The ALK rearrangement was confirmed not only in the primary tumor biopsy specimen, but also in the pleural effusion cell block by reverse transcriptase-polymerase chain reaction (RT-PCR), Ventana ALK immunohistochemistry assay, and fluorescence in situ hybridization. No clinical benefit using chemotherapy or EGFR tyrosine kinase inhibitor gefitinib was obtained in this case. PMID- 26273362 TI - Case report of polymorphous low-grade adenocarcinoma in the trachea with metastasis to the right middle lobe bronchus. AB - Polymorphous low-grade adenocarcinoma (PLGA) is a low-grade malignant infiltrative tumor of the minor salivary glands. According to data from PubMed (National Center for Biotechnology), one case of PLGA involving the left main bronchus and one case involving the right main and upper lobar bronchi have previously been reported. Here, we describe the first case of PLGA originating in the trachea with metastasis to the right middle lobe bronchus, all initially misdiagnosed as adenoid cystic carcinoma (ACC). It is particularly important to distinguish this tumor from other types of salivary gland tumors, especially ACC. Complete surgical excision is the curative treatment of choice for PLGA. PMID- 26273363 TI - Clinically beneficial continued treatment with gefitinib after asymptomatic progression of lung adenocarcinoma. AB - We report a case showing the long-term clinical benefit of the continued use of gefitinib in a patient with asymptomatic progression of lung adenocarcinoma harboring an exon 19 deletion of the epidermal growth factor receptor gene. Although follow-up studies showed smoldering progression of metastatic lesions, continued treatment with gefitinib controlled pulmonary adenocarcinoma for more than six years. PMID- 26273364 TI - Asymptomatic air-embolism following percutaneous radiofrequency ablation of lung tumor: Rare or underestimated complication? PMID- 26273365 TI - Subxyphoid single-incision thoracoscopic pulmonary metastasectomy. AB - Single-incision thoracoscopic surgery has increasingly attracted public interest and been applied in numerous thoracic procedures. However, single-incision thoracoscopic surgery is associated with requiring subsequent procedures, such as intercostal neuralgia. Herein, we extend the single-port technique of pulmonary metastasectomy through a single subxiphoid approach, and report the first two cases of this procedure to date. PMID- 26273367 TI - Current small cell lung cancer treatment in China. AB - BACKGROUND: The treatment status of small cell lung cancer (SCLC) in Mainland China has never been reported; therefore, this study is the first multicenter survey investigating the status of epidemiology and treatment options of SCLC in Mainland China. METHODS: Two questionnaires were designed to obtain information in 12 medical centers in five major Chinese cities. The hospital information questionnaire was designed to outline SCLC patients' characteristics and treatment preferences in each medical institution, and the patient information questionnaire collected detailed treatment information of 298 SCLC cases in these hospitals. RESULTS: SCLC represented 13.7% and 18.3% of all lung cancer patients in 2005 and 2010, respectively. Clinical management of SCLC follows mainstream clinical guidelines in general. The most widely applied first-line treatment mode for limited-stage patients was combined chemoradiotherapy (66.2%), while 77.0% of the extensive-stage patients received chemotherapy alone as initial treatment. Etoposide with cisplatin or carboplatin were the most accepted first-line chemotherapy regimens. The objective response rate was 58.3% after first-line chemotherapy and 23% of the patients who responded well to first-line treatment received prophylactic cranial irradiation. As for second-line chemotherapy, single regimen topotecan or a combined regimen containing topotecan were preferred (53.0%). CONCLUSIONS: The treatment options indicated in our study are in accordance with the international clinical guidelines, which is valuable for the improvement of future guidelines, health care standard, and even the better distribution of health care resources in China. PMID- 26273368 TI - Usefulness of target delineation based on the two extreme phases of a four dimensional computed tomography scan in stereotactic body radiation therapy for lung cancer. AB - BACKGROUND: An evaluation of the usefulness of target delineation based only on the two extreme phases of a four-dimensional computed tomography (4D CT) scan in lung stereotactic body radiation therapy (SBRT). METHODS: Seventeen patients treated with SBRT via 4D CT scans for lung cancer were retrospectively enrolled. Volumetric and geometric analyses were performed for the internal target volumes (ITVs) and planning target volumes (PTVs) generated using different respiratory phases (all phases and 2 extreme phases) and setup margins (3 mm and 5 mm). RESULTS: As the setup margins were added to the ITVs, the overlap percentage between the PTVs based on all phases and the two extreme phases increased (85.1% for ITVs, 89.8% for PTVs_3 mm, and 91.3% for PTVs_5 mm), and there were no differences according to the tumor parameters, such as the gross tumor volume and 3D mobility. The missing-volume differences for ITVs derived from cone-beam CT images also decreased, with values of 5.3% between ITVs, 0.5% between PTVs_3 mm, and 0.2% between PTVs_5 mm. Compared with the plan based on all phases and a 3 mm margin, the average lung-dose differences found for the PTV based on the two extreme phases and a 5 mm margin were 0.41 Gy for the mean lung dose and 0.93% for V20. CONCLUSIONS: Regardless of tumor characteristics, PTV construction based only on the two extreme phases and a 5 mm setup margin may be a useful tool for reducing the clinical workload involved in target delineation in SBRT for lung cancer. PMID- 26273369 TI - Chest wall tumors and prosthetic reconstruction: A comparative analysis on functional outcome. AB - BACKGROUND: To address the question of how much chest-wall (CW) resections and prosthetic reconstructions influence functional outcome. METHODS: We retrospectively reviewed 175 patients who underwent surgery for CW tumors. The clinical, histological, surgical, oncological, and functional factors were analyzed. RESULTS: We performed: 75 rib resections; 20 sternal resections; 15 combined resections; and 27 lung resections. In 39 cases (22.2%) CW was stabilized with non-rigid prosthesis (Vicryl-mesh: 8 patients; Goretex-mesh: 31 patients). Postoperative complications occurred in 22 cases (12.6%): a correlation with lung resection was evidenced by multivariate analysis (P = 0.025). Five-year survival for primary and secondary tumors was 50% and 36%, respectively: multivariate analysis (P = 0.048) showed a worse survival in men only. In the prosthesis subset, pulmonary function tested as percentage of forced expiratory volume in one second (%FEV1) (pre: 87.1 +/- 18.9%; post: 82.3 +/- 23.0%, P = ns), percentage of forced vital capacity (pre: 94.1 +/- 19.3%; post: 82.0 +/- 21.6%, P = ns), diffusing capacity of the lungs for carbon monoxide (pre: 15.7 +/- 7.4; post: 12.1 +/- 4.1, P = ns) and paO2 (pre: 82.6 +/- 10.9 mmHg; post: 83.9 +/- 7.3 mmHg, P = ns) was slightly modified from pre to postoperative. Interestingly, the decline of FEV1% was lower in the prosthesis subset (4.1 +/- 15.9%) compared with the subgroup who did not undergo prosthetic stabilization (17.5 +/- 16.2%), but this difference was not statistically significant (P = ns). CONCLUSION: Because of the low decrease of lung parameters, CW prosthetic reconstruction could be helpful for avoiding postoperative worsening of functional outcome, mostly in patients with pre-existing pulmonary diseases. PMID- 26273370 TI - Influence of different image-guided tracking methods upon the local efficacy of CyberKnife treatment in lung tumors. AB - BACKGROUND: The aim of this study was to explore the influence of image-guided tumor localization modality (Synchrony tracking vs. Xsight spine-based localization) on the local efficacy of CyberKnife treatment in lung cancer and lung metastases. METHODS: Retrospective analysis of 64 patients with pulmonary metastases and primary tumor cases (72 targets) treated with stereotactic body radiotherapy using CyberKnife was conducted. Synchrony respiratory tracking was used to treat 45 targets, and the remaining 27 targets were treated using Xsight spine (with an extended margin to account for positional uncertainty). The median (80%) isodose line (70-94%) covered the planning target volume at a total dose of 6000 cGy delivered in three fractions. Local efficacy was evaluated by Response Evaluation Criteria in Solid Tumors, accompanied by the follow-up of local recurrence cases and analysis of tracking methods. RESULTS: Short-term local control was superior for targets tracked with Synchrony than for targets localized with Xsight spine. There was no statistical difference for targets in the upper lung, but for targets in the lower lung Synchrony tracking was better. Small targets (less than 15 mL) were better controlled when Synchrony was used, but there was no difference for treatment volumes larger than 15 mL. Treatment failures were more likely in the lower lung and for small tumors localized with Xsight spine. CONCLUSIONS: The local efficacy of CyberKnife treatment in lung cancer and lung metastases was influenced by image-guided localization method, target location within the lung, and tumor volume. PMID- 26273371 TI - Inhibition of lung adenocarcinoma cells by insulin-like growth factor-I receptor and Kirsten rat sarcoma mutations: A mutation analysis with antisense oligodeoxynucleotide. AB - BACKGROUND: Kirsten rat sarcoma (KRAS) mutations are widespread in lung adenocarcinoma patients. The combined utilization of KRAS antisense oligodeoxynucleotide (ASODN) and insulin-like growth factor-I receptor (IGF-IR) may inhibit the proliferation of A549 cell lines of lung adenocarcinoma. METHODS: Point mutations of the KRAS gene in A549 cells were detected by polymerase chain reaction with special sequence primers (PCR-SSP) and gene sequence analysis; ASODN was designed and synthesized according to the mutation specialty of KRAS; and the correlation of gene mutations and clinicopathological features were analyzed. Inhibition on the proliferation and morphostructure change were measured by methyl thiazolyl tetrazolium and colony-forming unit assays. Flow cytometry was used to evaluate the expression of KRAS and IGF-IR proteins and cell apoptosis and reverse transcriptase-polymerase chain reaction were used to detect the expression of KRAS and IGF-IR messenger ribonucleic acid (mRNA). Male nude mice were used to form the mice-human lung cancer model and show the inhibition of KRAS ASODN on A549 cells. RESULTS: PCR-SSP and gene sequence analysis results showed that the codon 12 of KRAS had changed from GGT to GTT. KRAS ASODN or IGF-IR ASODN could inhibit cell proliferation and promote apoptosis of A549 cells. However, the combined utilization of KRAS ASODN and IGF-IR ASODN could inhibit cell proliferation and promote apoptosis more powerfully than exclusive use of KRAS ASODN or IGF-IR ASODN. CONCLUSION: The two ASODNs can inhibit the proliferation of lung adenocarcinoma cells through decreasing the expression of KRAS and IGF-IR mRNA and protein. PMID- 26273372 TI - Prevalence and clinical significance of BRAF V600E in Chinese patients with lung adenocarcinoma. AB - BACKGROUND: The purpose of this study was to investigate the prevalence, distribution, and prognostic role of v-raf murine sarcoma viral oncogene homolog B (BRAF) V600E mutations in Chinese patients with lung adenocarcinoma (ADC), and to explore the possibility of BRAF V600E mutation detection in plasma DNA. METHODS: Data from 190 patients with lung ADCs treated at the Peking University Cancer Hospital from July 2011 to March 2012 were collected. The amplification refractory mutation system was used for BRAF V600E testing and denaturing high performance liquid chromatography for epidermal growth factor receptor (EGFR) mutation detection. In BRAF V600E-mutant cases, paired plasma DNA was tested for mutation status of BRAF V600E and EGFR. The distribution and prognostic role of BRAF V600E mutations were analyzed using SPSS 13.0. RESULTS: Among 190 patients with advanced lung ADC, eight (4.2%) cases carried BRAF V600E mutations. V600E mutations presented more frequently in women than in men (6 of 96, 6.3% vs. P = 0.1). BRAF and EGFR mutations were concomitantly presented in three patients. Five of the eight patients with BRAF V600E mutations had matched plasma DNA samples and V600E mutations were found in three plasma samples. CONCLUSION: The prevalence of BRAF V600E mutations in Chinese patients with lung ADC is 4.2%. Circulating plasma DNA may be used for BRAF V600E mutation analysis in lung adenocarcinoma. PMID- 26273373 TI - Combination of platelet to lymphocyte ratio and neutrophil to lymphocyte ratio is a useful prognostic factor in advanced non-small cell lung cancer patients. AB - BACKGROUND: The neutrophil to lymphocyte ratio (NLR) was recently shown to be a remarkable prognostic factor in tumors. Moreover, some studies have indicated that the combination of NLR and platelet to lymphocyte ratio (PLR) could be a better prognostic factor. As the combined prognostic value of NLR and PLR in non small cell lung cancer (NSCLC) is not clear, we conducted this study to explore this further. METHODS: A total of 366 primary NSCLC patients with stage III or IV were finally included. The neutrophil, platelet, and lymphocyte counts were recorded before treatment was initiated. NLR and PLR were calculated and NLR > 2.68 or PLR > 119.50 was defined as elevated. Univariate and multivariate survival analyses were conducted to test their prognostic value. RESULTS: The median of NLR and PLR were 3.14 and 152.63, respectively, in all patients. It was indicated that PLR is linearly associated with NLR. PLR is associated with survival, but is not an independent prognostic factor. Removing NLR, PLR is an independent prognostic factor (overall survival [OS]: hazard ratio [HR] = 1.918, P = 0.003; progression-free survival [PFS]: HR = 1.822, P = 0.007 in condition of NLR <= 2.68). It was also indicated that elevated NLR is an independent prognostic factor (OS: HR = 1.778, P = 0.009; PFS: HR = 1.535, P = 0.022) in all patients. CONCLUSIONS: PLR is a useful complement of NLR, thus, advanced NSCLC patients could be divided into three prognostic groups prior to treatment: poor: NLR > 2.68; moderate: NLR <= 2.68 and PLR > 119.50; and good: NLR <= 2.68 and PLR <= 119.50. PMID- 26273374 TI - Expression of p63 and CK5/6 in early-stage lung squamous cell carcinoma is not only an early diagnostic indicator but also correlates with a good prognosis. AB - BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for 80% of lung cancers, and lung squamous cell carcinoma (SQCC) is one of the main types. Advances in the treatment of lung SQCC are lacking when compared to lung adenocarcinoma. The main treatment for early-stage SQCC is surgery. However, factors affecting the efficacy of surgical treatments for early-stage lung SQCC remain unclear. In this study, we examined the significance of commonly used lung SQCC diagnostic markers p63, p40, and cytokeratin (CK)5/6 in prognosis. METHODS: Seventy-six cases of early-stage lung SQCC (N0) were obtained from our lung cancer database (January 2000 to December 2009). Tissue microarray and immunohistochemical (IHC) staining were used to detect the expression of p63, p40, and CK5/6. The effect of the expression level of each marker on patients' survival was examined. RESULTS: Sensitivity and specificity of each marker for detecting lung SQCC was 87.0% and 81.0% for p63, 75.9% and 97.9% for p40, and 78.9% and 97.7% for CK5/6. Survival rates of patients with high expression levels of p63 or CK5/6 or both were higher than in patients with low expression levels (P < 0.05). Expression levels of p40 had no effect on survival (P > 0.05). Multivariate analysis showed that high levels of p63 expression p63+CK5/6 co-expression were independent prognostic factors for good survival. CONCLUSION: IHC staining detection of p63 and CK5/6 in specimens should be routinely performed in postoperative early-stage lung SQCC patients. Its significance lies not only in differential diagnosis, but also in determining prognosis. PMID- 26273375 TI - Alternative method for jejunostomy in Ivor-Lewis esophagectomy. AB - BACKGROUND: To supplement nutrition, jejunostomy has been widely adopted as an adjunct surgical procedure for Ivor-Lewis esophagectomy. Most Chinese surgeons have a preference for parenteral nutrition even though it has some disadvantages compared with jejunostomy. In this report, we describe a new approach that allows the quick insertion of a feeding tube in Ivor-Lewis esophagectomy. We retrospectively analyze cases that have applied this approach and compare the advantages and disadvantages of jejunostomy. METHODS: Between January 2010 and December 2012, 131 patients underwent Ivor-Lewis esophagectomy in our hospital. These patients were divided into three groups: the total parenteral nutrition (PN) group, the jejunostomy (JT) group and the feeding tube (FT) group. The effect and safety of the procedure were compared. RESULTS: It took approximately 20 minutes longer to perform jejunostomy compared to placing a feeding tube (P < 0.05). The nutrition cost of the JT group was higher than the FT group (P < 0.05). There was no significant difference between the FT and JT groups (P > 0.05) in the ratio of body weight loss seven days post-surgery. The anal exsufflation time of the FT group was similar to the JT group (P > 0.05). The incidence of intestinal adhesion and obstruction in the JT group was 26.3%, which is much higher than in the FT and PN groups (P < 0.05). CONCLUSION: Placing the feeding tube after Ivor-Lewis esophagectomy can decrease operative damage and bring sufficient nutrition. We believe it can be an alternative to jejunostomy in Ivor-Lewis esophagectomy. PMID- 26273376 TI - Comparison of perioperative outcomes between open and minimally invasive esophagectomy for esophageal cancer. AB - BACKGROUND: To compare surgical outcomes of thoracoscopic and laparoscopic esophagectomy with open esophagectomy in order to study the learning curve of minimally invasive surgery for esophageal cancers. METHODS: Among 109 esophageal cancer patients retrospectively studied, 59 patients underwent minimally invasive esophagectomy (MIE) and 50 underwent open surgery (OE). In the MIE group, the first 30 patients received hybrid procedures, including 16 thoracoscopic esophagectomies and 14 laparoscopic maneuvers. The later 29 patients received thoraco-laparoscopic esophagectomy (TLE). RESULTS: The overall morbidity of MIE and OE was 42.4% (25/59) and 44.0% (22/50), respectively, with no statistical difference. However, the MIE group had a significantly lower incidence of functional complication (1.79%, 1/59) than the OE group (32.0%, 16/50, P < 0.01). The technical complication rate was not significantly different between the two groups (14/59, 23.7% vs. 6/50, 12.0%, P = NS), nor was the overall complication rate between the 30 early period cases and the 29 later cases (P = NS); although the later cases had TLE and there was no recurrent laryngeal nerve injury. CONCLUSION: Minimally invasive approaches may help to decrease the risk of functional complication but not technical problems, after esophagectomy. For esophageal cancer patients to benefit from this minimally invasive surgery, an extended learning curve is necessary to avoid technical problems, such as anastomotic leakage and recurrent laryngeal nerve palsy. PMID- 26273377 TI - Traffic-related air pollution and lung cancer: A meta-analysis. AB - BACKGROUND: We conducted a meta-analysis to evaluate the association between traffic-related air pollution and lung cancer in order to provide evidence for control of traffic-related air pollution. METHODS: Several databases were searched for relevant studies up to December 2013. The quality of articles obtained was evaluated by the Strengthening the Reporting of Observational Studies in Epidemiology checklist. Statistical analysis, including pooling effective sizes and confidential intervals, was performed. RESULTS: A total of 1106 records were obtained through the database and 36 studies were included in our analysis. Among the studies included, 14 evaluated the association between ambient exposure to traffic-related air pollution and lung cancer and 22 studies involved occupational exposure to air pollution among professional drivers. Twenty-two studies were marked A level regarding quality, 13 were B level, and one was C level. Exposure to nitrogen dioxide (meta-odds ratio [OR]: 1.06, 95% confidence interval [CI]: 0.99-1.13), nitrogen oxide (meta-OR: 1.04, 95% CI: 1.01 1.07), sulfur dioxide (meta-OR: 1.03, 95% CI: 1.02-1.05), and fine particulate matter (meta-OR: 1.11, 95% CI: 1.00-1.22) were positively associated with a risk of lung cancer. Occupational exposure to air pollution among professional drivers significantly increased the incidence (meta-OR: 1.27, 95% CI: 1.19-1.36) and mortality of lung cancer (meta-OR: 1.14, 95% CI: 1.04-1.26). CONCLUSION: Exposure to traffic-related air pollution significantly increased the risk of lung cancer. PMID- 26273378 TI - Epidermal growth factor receptor variant III mutation in Chinese patients with squamous cell cancer of the lung. AB - BACKGROUND: The aim of this study was to investigate the distribution of epidermal growth factor receptor (EGFR)vIII mutation in Chinese non-small cell lung cancer (NSCLC) patients and to explore the likely relationship between EGFRvIII mutation and response to EGFR-tyrosine kinase inhibitors (TKIs) in squamous cell carcinoma (SCC). METHODS: Samples were derived from two patient cohorts: (i) 114 early-stage NSCLC who received surgical resection; and (ii) 31 advanced-stage SCC who received EGFR-TKI EGFRvIII. EGFR and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations were detected by reverse transcription polymerase chain reaction (RT-PCR), denaturing high-performance liquid chromatography, and PCR-restriction fragment length polymorphism, respectively. The associations of EGFRvIII, EGFR, and KRAS mutations with clinical outcome of EGFR-TKI treatment were evaluated using the Kaplan-Meier method, descriptive analysis, and multi-variable Cox regression analysis. RESULTS: In the first cohort, EGFRvIII mutation was detected in eight of 114 (7.0%) patients, including 11.1% (6/54) SCC and 3.6% (2/55) adenocarcinomas (ADC) (P = 0.269). In the second cohort, five (16.1%) and 10 out of 31 advanced SCC presented EGFRvIII and EGFR mutations, respectively. No appreciable discrepancy of progression-free survival or disease control rate was detected between the patients with and without EGFRvIII mutation (P > 0.05). However, longer median overall survival (OS) was observed in patients harboring EGFRvIII compared to those without EGFRvIII, although the difference did not reach statistical significance. CONCLUSION: The frequency of EGFRvIII mutation in SCC was higher than in ADC. SCC patients harboring EGFRvIII mutations had a tendency for prolonged OS. PMID- 26273379 TI - Percutaneous radiofrequency ablation for medically inoperable patients with clinical stage I non-small cell lung cancer. AB - BACKGROUND: A retrospective evaluation of percutaneous radiofrequency ablation (RFA) in medically inoperable patients with clinical stage I non-small cell lung cancer (NSCLC). METHODS: Between 2008 and 2014, 29 medically inoperable patients with clinical stage I NSCLC underwent percutaneous RFA. We evaluated the feasibility, safety, and effectiveness. RESULTS: There were 18 men and 11 women with a median age of 78.0 years (range 56-85), mean 76.0 years. No procedure related deaths occurred in any of the 33 ablation procedures. The mean follow-up was 25 months. The incidence of local tumor progression was 21.0% at 25 months of median time to progression after the initial RFA. The mean overall survival (OS) was 57 months (95% confidence interval (CI) 44-70 months). The mean cancer specific survival CSS was 63 months (95% CI 50-75 months). OS was 90.5% +/- 6.4% at one year, 76.4% +/- 10.7% at two, and 65.5% +/- 13.6% at three years. CSS was 95.2% +/- 4.6% at one, 86.6% +/- 9.3% at two, and 74.2% +/- 13.9% at three years in all patients. The survival for stage IA and IB cancers were 87.5% and 92.3% at one, 87.5% and 73.4% at two, and 87.5% and 58.7% at three years, respectively. Survival rates were not significantly different between the two groups (P = 0.596), with mean survival times of 65 (95% CI: 51-79 months) and 55 months (95% CI: 38-71 months), respectively. CONCLUSION: Percutaneous RFA is a safe, feasible, and effective procedure in medically inoperable clinical stage I NSCLC patients. PMID- 26273380 TI - Self-reported depression among patients with non-small cell lung cancer. AB - BACKGROUND: Lung cancer is a disease with a poor prognosis and psychological impact. Lung cancer causes both physical and psychological burdens on patients, and financial burdens on families and society. The aim of this study was to examine the relationship between depression and influencing factors in non-small cell lung cancer (NSCLC) patients. METHODS: A quantitative study was applied. Data was obtained from the Shanghai Pulmonary Hospital in China. One hundred and four patients with NSCLC were surveyed. Self-rating depression scale (SDS), social support rating scale (SSRS), and visual analog scale (VAS) were used. RESULTS: Among the 104 patients, 48 (46.1%) were diagnosed with depression. Gender (P = 0.000), disease duration (P = 0.006), self-care ability (P = 0.004), and pain (P = 0.003) were statistically significant predictors of self-reported depression in non-small-cell lung cancer patients. CONCLUSIONS: Self-reported depression is highly prevalent in NSCLC patients. In addition, gender, disease duration, self-care ability, pain and social support may increase self-reported depression. PMID- 26273381 TI - Analysis of the factors influencing lung cancer hospitalization expenses using data mining. AB - BACKGROUND: Hospitalization expenses for the therapy of lung cancer are not only a direct economic burden on patients, but also the focus of medical insurance departments. Therefore, the method for classifying and analyzing lung cancer hospitalization expenses so as to predict reasonable medical cost has become an issue of common interest for both hospitals and insurance institutions. METHODS: A C5.0 algorithm is adopted to analyze factors influencing hospitalization expenses of 731 lung cancer patients. A C5.0 algorithm is a data mining method used to classify calculation. RESULTS: Increasing the number of input variables leads to variation in the importance of different variables, but length of stay (LOS), major therapy, and medicine cost are the three variables of greater importance. They are important factors that affect the hospitalization cost of lung cancer patients. In all three calculations, the classification accuracy rate of training and testing partition sets reached 84% and above. The classification accuracy rate reached over 95% after addition of the cost variables. CONCLUSION: The classification rules are proven to be in accordance with actual clinical practice. The model established by the research can also be applied to other diseases in the screening and analysis of disease hospitalization costs according to selected feature variables. PMID- 26273382 TI - Selection of proper candidates with resected pathological stage IIIA-N2 non-small cell lung cancer for postoperative radiotherapy. AB - BACKGROUND: To establish a prediction model in selecting fit patients with resected pIIIA-N2 non-small cell lung cancer (NSCLC) for postoperative radiotherapy (PORT), and evaluate the model in clinical practice. METHODS: Between January 2003 and December 2005, 221 patients with resected pIIIA-N2 NSCLC were retrospectively analyzed. The effect of PORT on overall survival (OS) of patients with different clinicopathological factors was evaluated and the results were used to establish a prediction model to select patients fit for PORT. RESULTS: Compared with the control, PORT significantly improved the OS of patients with a smoking index <=400 (P = 0.033), cN2 (P = 0.003), pT3 (P = 0.014), squamous cell carcinoma (SCC) (P = 0.013), or >=4 positive nodes (P = 0.025). Patients were divided from zero to all five factors into low, middle, and high PORT index (PORT-I) groups (scored 0-1, 2, and 3-5, respectively). PORT did not improve OS (3-year, P = 0.531), disease free survival (DFS) (P = 0.358), or loco-regional recurrence free survival (LRFS) (P = 0.412) in the low PORT-I group. PORT significantly improved OS (P = 0.033), and tended to improve DFS (P = 0.064), but not LRFS (P = 0.287) in the middle PORT-I group. PORT could significantly improve OS (P = 0.000), DFS (P = 0.000), and LRFS (P = 0.006) in the high PORT-I group. CONCLUSION: The prediction model is valuable in selecting patients with resected pIIIA-N2 NSCLC fit for PORT. PORT is strongly recommended for patients with three or more of the five factors of smoking index <=400, cN2, pT3, SCC, and >=4 positive nodes. PMID- 26273383 TI - Incidence and management of chylothorax after esophagectomy. AB - BACKGROUND: Chylothorax is a rare but serious postoperative complication in esophageal cancer patients. The aim of this study was to identify risk factors associated with chylothorax and the indication for surgical intervention. METHODS: A consecutive series of 1290 patients who underwent esophagectomy for esophageal cancer was included. Peri-operative data, including postoperative morbidity and mortality, were analyzed. RESULTS: Thirty-four patients (2.6%) developed chylothorax and had significantly higher instances of pneumonia (26.5% vs. 11.1%, P = 0.012) and arrhythmia (17.6% vs. 2.9%, P = 0.001), and a longer hospital stay (22 vs. 18 days, P < 0.001). Reoperation was performed in 11 patients at a rate of 77.8%, 42.9%, 20%, and 0% for chylothorax diagnosed in two, three, four, and >= 5 days, respectively, after esophagectomy (P < 0.001). After three days of conservative therapy, the chest tube output was significantly greater in patients whose medical management had failed than in those successfully treated (P < 0.001). All patients who required reoperation had >= 13.5 ml/kg of drainage (sensitivity 100%); four of 23 patients with successful medical management had a chest tube output >= 13.5 ml/kg (specificity 83%). Logistic regression analysis showed that body mass index (BMI) < 25 was an independent risk factor for chylothorax (hazard ratio = 9.256, P = 0.029). CONCLUSIONS: Patients with a BMI < 25 are more likely to develop chylothorax after esophagectomy. Operative therapy should be seriously considered in patients who develop chylothorax early postoperatively. In addition, a high daily chylous output of >= 13.5 ml/kg after three days of conservative therapy might be a reliable indicator for reoperation. PMID- 26273384 TI - Myelomatous pleural effusion involvement in 23 patients with multiple myeloma: A single-center clinical analysis. AB - We investigated the treatment and prognosis of pleural effusion (PE) in multiple myeloma (MM) patients. From June 2005 to December 2013, 296 MM patients participated in this study. There were 23 PE patients, including 11 men and 12 women, with a median age of 56.8 years (range 37-68 years). A diagnosis of PE was based on physical examination, chest X-ray or computed tomography, and pleural fluid analysis. All patients demonstrated myeloma cells in the pleural fluid, and six patients were positive for PE M protein. PE patients received bortezomib combined with other drugs. Only one patient demonstrated a complete response; 10 patients showed partial responses, and 12 patients developed progressive disease and died. MM linked with myelomatous PE is associated with a poor prognosis. Myelomatous PE is likely a late manifestation of the natural history of MM or an expression of the aggressive behavior of the disease. PMID- 26273385 TI - Differential diagnosis and cancer staging of a unique case with multiple nodules in the lung - lung adenocarcinoma, metastasis of colon adenocarcinoma, and colon adenocarcinoma metastasizing to lung adenocarcinoma. AB - Lung cancer is the most common cancer in the world. Despite this, there have been few cases of simultaneous primary and metastatic cancers in the lung reported, let alone coexisting with tumor-to-tumor metastasis. Herein, we describe an extremely unusual case. A 61-year-old man with a history of colon adenocarcinoma was revealed as having three nodules in the lung 11 months after colectomy. The nodule in the left upper lobe was primary lung adenocarcinoma, the larger one in the right upper lobe was a metastasis of colon adenocarcinoma, and the smaller one in the right upper lobe was colon adenocarcinoma metastasizing to lung adenocarcinoma. Our paper focused on the differential diagnosis and cancer staging of this unique case, and discussed the uncommon phenomenon of the lung acting as a recipient in tumor-to-tumor metastasis. PMID- 26273386 TI - Giant solitary fibrous tumor of the pleura: A case report. AB - A 62-year-old male farmer weighing 79 kg was taken to a hospital after experiencing exertional dyspnea and shortness of breath for a month. A chest roentgenogram and computed tomography showed a giant mass in his right thorax. A CT-guided biopsy demonstrated a solitary fibrous tumor of the pleura (SFTP). Because of the large size of the tumor and the substantial pleural effusion in the right hemithorax, the patient was referred to our institution for radiofrequency ablation. After one month, we performed an exploratory thoracotomy to dissect the giant mass with the right, middle, and lower lobes. The measurement of the tumor was 20 cm * 18 cm * 13 cm and it weighed 3250 g. The histopathology of the resected specimen confirmed SFTP. The patient had no postoperative complications; six months after surgery, no recurrence occurred. PMID- 26273387 TI - Medical thoracoscopy in MALT lymphoma causing pleural effusion: A case report. AB - Mucosa-associated lymphoid tissue (MALT) lymphoma is a form of low-grade malignant B-cell extranodal non-Hodgkin's lymphoma. It is classified as marginal zone lymphoma and represents less than 1% of all lung cancer. We describe a case of MALT lymphoma limited exclusively to the lung that came to our attention with infective pleural effusion and concomitant lung consolidation of the left lower lobe. Our case demonstrates that MALT can begin with an acute clinical presentation. The clinical scenario, with fever, parietal chest pain, and leukocytosis, suggested an infective process. Radiological and sonographic examinations and the endoscopic aspect during medical thoracoscopy (MT) were typical of an infective etiology. The histological outcome of non-specific inflammatory pleuritis confirmed our suppositions. However, the missing resolution of lung consolidation after several weeks led us to an alternative diagnosis. Parenchymal biopsies obtained by bronchoscopy allowed us to reach the correct diagnosis: MALT lymphoma limited to the lung. PMID- 26273388 TI - Thymectomy and transpericardial nodal dissection. AB - Neuroendocrine thymic tumors (NETTs) are rare neoplasms. Surgical resection of the tumor and the involved lymph node remains the treatment of choice. We describe the surgical technique adopted in a patient with preoperative diagnosis of thymic malignant tumor and subcarinal nodal involvement. Through a median sternotomy, an extended thymectomy was performed as a first step. Then, through the transpericardial approach (opening of the anterior and posterior pericardium and isolation of ascending aorta, superior vena cava, and main right pulmonary artery), mediastinal nodal dissection (#2R, #4R, #4L, #5 and #7) was performed. Definitive pathology showed a NETT without nodal involvement. The patient received adjuvant chemotherapy, and is alive without disease 19 months after the surgery. Complete surgical excision and adjuvant therapy appears to offer the best hope for prolonged survival for NETTs. The surgical technique should be individualized according to tumor location. Thoracic surgeons should be familiar with this technique, which provides a good technical and oncological result. PMID- 26273390 TI - Clinical experiences with molecular targeted therapy in lung cancer in China. AB - In the past decade, a dramatic shift has been witnessed in cancer therapy in China. Although traditional cytotoxic chemotherapy still remains the treatment of choice for many malignancies, targeted therapies are now a component of treatment for many types of cancer, including lung cancer. As molecular target agents are widely used in clinical practice and relevant studies have been conducted, we have accumulated valuable experience in the treatment strategy for advanced non small cell lung cancer. On this basis we have successfully developed our Class-I new drug through independent research, which significantly accelerates the clinical development of targeted therapy for lung cancer. This article summarizes the clinical practice and relevant studies of current targeted therapies for lung cancer in China. PMID- 26273391 TI - Early detection of lung cancer: Low-dose computed tomography screening in China. AB - Lung cancer is currently the leading cause of cancer-related death in China and western countries for both men and women. Overall, the five-year survival rate of lung cancer is approximately 15%, whereas the five-year survival for patients with surgically resected early-stage disease is 60-80%. Screening is conceptually a good strategy for reducing the mortality rate of lung cancer. Randomized controlled trials in the 1960s and 1970s found that chest radiographic screening did not result in a reduction in mortality for high-risk individuals. Recently published data from the National Lung Screening Trial (NLST) showed a 20% reduction in lung cancer mortality in subjects who underwent low-dose computed tomography (LDCT) screening compared to those randomized to conventional chest X ray. The encouraging results of the NLST, however, could not be confirmed by the preliminary results of ongoing European trials. More results from European randomized controlled trials are expected in the next few years. Recently, a number of lung cancer screening studies using LDCT have been initiated in China. This article briefly summarizes the results of the current and previous lung cancer screening trials worldwide, and focuses on the current status of LDCT lung cancer screening in China. PMID- 26273393 TI - Role of radiotherapy in treating patients with primary malignant mediastinal non seminomatous germ cell tumor: A 21-year experience at a single institution. AB - BACKGROUND: The aim of this study was to investigate the clinical characteristics and outcomes of patients with primary malignant mediastinal non-seminomatous germ cell tumor (MMNSGCT) by comparing the efficacies of different treatment modalities. METHODS: The charts of 62 consecutive patients with MMNSGCT between 1990 and 2010 were reviewed. Analyses included Kaplan-Meier survival and Cox multivariate regression. RESULTS: There was sufficient data of 61 patients for inclusion in the study. The median age was 25 years. At diagnosis, 35 patients had tumors located in the mediastinum, 26 had lung and/or distant metastases. At a median follow-up of 47.2 months, 32 patients had died and 43 had developed progressive disease. The one, three, and five-year overall survival (OS) and progression-free survival (PFS) rates were 72.1%, 50.8%, 49.2% and 47.5%, 32.8%, 32.8%, respectively. Patients who received radiotherapy in the primary treatment regimen showed improved five-year OS (68.2% vs. 38.5%, P = 0.043), PFS (45.5% vs. 20.5%, P = 0.023), and local recurrence-free survival (LRFS) (77.3% vs. 38.5%, P = 0.003) compared with those who did not receive radiotherapy. Multivariate analysis revealed that radiotherapy was an independent prognostic factor of five year OS (hazard ratio [HR] 0.39, P = 0.037), PFS (HR 0.42, P = 0.017), and LRFS (HR 0.31, P = 0.019). CONCLUSION: Radiotherapy in a chemotherapy-based treatment regimen could significantly reduce local recurrence and improve survival of MMNGCT patients. PMID- 26273392 TI - Role of acetylcholinesterase in lung cancer. AB - Acetylcholinesterase (AChE) plays a key role in catalytic hydrolysis of cholinergic neurotransmitters. Intensive research has proven the involvement of this protein in novel functions, such as cell adhesion, differentiation, and proliferation. In addition, several recent studies have indicated that acetylcholinesterase is potentially a marker and regulator of apoptosis. Importantly, AChE is also a promising tumor suppressor. In this review, we briefly summarize the involvement of AChE in apoptosis and cancer, focusing on the role of AChE in lung cancer, as well as the therapeutic consideration of AChE for cancer therapy. PMID- 26273394 TI - Treatment and prognostic analysis of patients with leptomeningeal metastases from non-small cell lung cancer. AB - BACKGROUND: Leptomeningeal metastases (LM) from non-small cell lung cancer (NSCLC) are associated with poor prognosis and optimal treatment for this subgroup of NSCLC patients is controversial. The purpose of this study is to evaluate treatment options and prognostic factors of NSCLC patients with LM. METHODS: We retrospectively analyzed data of 108 patients who had been diagnosed with LM from NSCLC between May 2006 and August 2013. RESULTS: The median survival time (MST) of the 108 patients was 5.3 months, and the one-year survival rate was 23.7%. Forty-nine patients received whole brain radiotherapy (WBRT) and the MST of patients who received WBRT and those who did not were 6.4 and 4.3 months, respectively. Forty-two patients were treated with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) after being diagnosed with LM. These patients had prolonged survival (11.1 vs. 4.4 months). Patients who received concomitant WBRT and EGFR-TKIs had the longest MST (12.3 months). Eastern Cooperative Oncology Group performance status, whether patients received WBRT, and/or EGFR-TKIs were independent prognostic factors for patients with LM from NSCLC. CONCLUSION: WBRT, EGFR-TKIs or combined therapy, could lead to better clinical outcomes for NSCLC patients with LM. EGFR-TKIs plus WBRT has the potential to be the standard strategy for LM in NSCLC patients. PMID- 26273395 TI - Clinicopathological characteristics and outcomes of ROS1-rearranged patients with lung adenocarcinoma without EGFR, KRAS mutations and ALK rearrangements. AB - BACKGROUND: c-ros oncogene 1 (ROS1) rearrangement presents one of the newest molecular targets in non-small cell lung cancer (NSCLC). ROS1 rearrangement is predominantly found in adenocarcinoma cases and is exclusive to other oncogenes, such as epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), and anaplastic lymphoma kinase (ALK). The aim of this study was to investigate the clinicopathological characteristics and outcomes of ROS1-rearranged patients with lung adenocarcinoma without EGFR and KRAS mutations and ALK rearrangements. METHODS: Wild-type EGFR/KRAS/ALK patients with lung adenocarcinoma were selected from Beijing Chest Hospital. Specimens were conducted in tissue microarrays. ROS1 rearrangement was screened using fluorescence in situ hybridization. RESULTS: Our study included 127 patients with lung adenocarcinoma without EGFR and KRAS mutations and ALK rearrangements. ROS1 rearrangement was detected in five (3.9%) of the 127 patients. Compared with ROS1 negative patients, the positive rate of ROS1 in female patients was significantly higher than in male patients (9.8% vs. 0.0%, P = 0.009). There were no differences in age, smoking status, stage or histological subtype between ROS1 positive and ROS1-negative patients. No significant difference in survival was detected between the ROS1-positive and ROS1-negative patients. CONCLUSIONS: ROS1 rearrangement is a rare subset of lung adenocarcinoma. In 127 patients with lung adenocarcinoma, 3.9% of ROS1-positive patients with wild-type EGFR/KRAS/ALK were found. PMID- 26273396 TI - Loss expression of micro ribonucleic acid (miRNA)-200c induces adverse post surgical prognosis of advanced stage non-small cell lung carcinoma and its potential relationship with ETAR messenger RNA. AB - BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. As micro ribonucleic acid (miRNA)-200 and ETAR may play an essential role in the process of epithelial to mesenchymal transition (EMT) simultaneously, the purpose of this study was to detect the expression of miRNA 200c and ETAR messenger (m)RNA and assess their prognostic significance in early stage NSCLC. METHODS: Our study included 78 advanced stage (IIB, IIIA, IIIB) NSCLC patients. All patients were smokers. Using quantitative reverse transcriptase polymerase chain reaction analysis, we detected the expression of miRNA-200c and ETAR mRNA and assessed their correlation by chi(2) test. Time to progression was used as the recurrent index and was assessed by univariate and multivariate analysis in the Cox hazard model. RESULTS: Both miRNA-200c and ETAR mRNA expression are associated with N stage and tumor node metastasis (TNM) stage in a series of advanced NSCLC patients. Among N stage and TNM stage patients, significant differences were found in IIB (P = 0.0126), IIIB (P = 0.0107) and N0 (P = 0.0023) and in N1 + N2 groups (P = 0.0133). Using both univariate and multivariate survival analyses, we found that miRNA-200c (hazard ratio [HR] = 0.352, 95% confidence interval [CI]: 0.187-0.662) and ETAR mRNA (HR = 2.500 95% CI: 1.345-4.647) were independent prognostic factors, independent of TNM stage (HR = 2.414, 95% CI: 1.600-3.642) and differentiation (HR = 1.530, 95% CI: 1.050 2230). CONCLUSIONS: miRNA-200c induces an expedient surgical survival, whereas ETAR mRNA has the reverse prognosis in advanced stage NSCLC patients. A potential relationship exists in that miRNA-200c targets ETAR mRNA during EMT. PMID- 26273397 TI - Overexpression of eukaryotic translation initiation factor 4E-binding protein 1 induces the alteration of immune status in H1299 lung cancer cells. AB - BACKGROUND: Eukaryotic translation initiation factor 4E-binding protein 1 (4E BP1) is an important factor regulating protein translation. It also impacts proliferation, apoptosis, invasion, and the cell cycle of cancer cells. The aim of this study was to investigate the relationship between 4E-BP1 and human immune status, recognizing immunomodulatory molecules involved in the overexpression of 4E-BP1. METHODS: A lentivirus expression system was used to overexpress 4E-BP1 in the H1299 cell line. Western blot was performed to investigate the expression level of 4E-BP1 and P-4E-BP1, and quantitative polymerase chain reaction was used to quantify gene expression of immunomodulatory molecules. RESULTS: The expression level of 4E-BP1 increased significantly after lentivirus infection (P < 0.05). Overexpression of 4E-BP1 upregulated the expression of interleukin (IL) 1beta (P < 0.05), IL-5 (P < 0.001), IL-23 (P < 0.001), macrophage inflammatory protein-1beta (P < 0.001), Eota-3 (P < 0.05), and MCP-4 (P < 0.05). Most of the increases were observed at the seventh day. The variation trend of IL-10, cell division cycle protein 2, proliferating cell nuclear antigen, and phosphatase and tensin homolog was not clear. CONCLUSION: Overexpression of 4E-BP1 altered immune status by upregulating the expression of a series of immunomodulatory molecules, indicating that 4E-BP1 could serve as a potential therapeutic target against cancer. PMID- 26273398 TI - Conflicting or complementary role of computed tomography (CT) and positron emission tomography (PET)/CT in the assessment of thymic cancer and thymoma: our experience and literature review. AB - BACKGROUND: To evaluate the role of computed tomography (CT) and positron emission tomography (PET)/CT in patients with thymic cancer and thymoma at initial staging. METHODS: We retrospectively reviewed CT and PET/CT scans of 26 patients with a thymic cancer (n = 9) or thymoma (n = 17). Chest CT findings documented were qualitative and quantitative. Both qualitative and semiquantitative data were recovered by PET/CT. The comparisons among histological entities, outcome, and qualitative data from CT and PET/CT were made by non-parametric analysis. RESULTS: PET/CT resulted positive in 15/17 patients with thymoma. CT was available in 5/9 (56%) patients with thymic cancer and in 3/17 with thymoma. All quantitative CT parameters were significantly higher in patients with thymic cancer than thymoma (maximum axial diameter: 45 vs. 20 mm, maximum longitudinal diameter: 69 vs. 21 mm and volume: 77.91 vs. 4.52 mL; all P < 0.05). Conversely, only metabolic tumor volume (MTV) and total lesion glycolysis were significantly different in patients with thymic cancer than thymoma (126.53 vs. 6.03 cm3 and 246.05 vs. 20.32, respectively; both P < 0.05). After a median follow-up time of 17.45 months, four recurrences of disease occurred: three in patients with thymic cancer and one with a type B2 thymoma. CT volume in patients with recurrent disease was 102.19 mL versus a median value of 62.5 mL in six disease-free patients. MTV was higher in the recurrent than disease-free patient subset (143.3 vs. 81.13 cm(3)), although not statistically significant (P = 0.075). CONCLUSION: Our preliminary results demonstrated that both morphological and metabolic volume could be useful from a diagnostic and prognostic point of view in thymic cancer and thymoma patients. A large multi center clinical trial experience for confirming the findings of this study seems mandatory. PMID- 26273399 TI - Cardiopulmonary exercise testing screening and pre-operative pulmonary rehabilitation reduce postoperative complications and improve fast-track recovery after lung cancer surgery: A study for 342 cases. AB - BACKGROUND: An evaluation of cardiopulmonary exercise testing (CPET) screening and pre-operative pulmonary rehabilitation in reducing postoperative complications and improving fast-track recovery in high-risk patients who undergo resection for lung cancer. METHODS: Of 342 potential lung cancer cases, 142 high risk patients were finally divided into two groups: group R (n = 71) underwent an intensive pre-operative pulmonary rehabilitation program (PRP), followed by lobectomy; group S (n = 71) underwent only lobectomy with conventional management. Postoperative complications, average days in hospital, postoperative days in hospital, and cost were analyzed. RESULTS: The 142 high-risk patients were screened by smoking history and CPET. Sixty-eight patients had bronchial hyperresponsiveness (BHR) and 47 patients had peak expiratory flow <250 L/minute by CPET. The rate of postoperative total complications in group R (16.90%) was significantly lower than in group S (83.31%) (P = 0.00), as was the rate of postoperative pulmonary complications PPC: group R (12.81%) versus S (13.55%) (P = 0.009); the PPC in the left lung (17.9%) was higher than in the right lung (2.3%) (P = 0.00). The average days in hospital in group S was significantly higher than in group R (P = 0.03). There was no difference between groups in average hospital cost (P = 0.304). CONCLUSION: Pre-operative screening using CPET is conducive to identifying high-risk patients for lung resection. Pre-operative pulmonary rehabilitation is helpful to reduce postoperative complications and improve fast-track recovery. PMID- 26273400 TI - Basic fibroblast growth factor shows prognostic impact on survival in operable non-small cell lung cancer patients. AB - BACKGROUND: The important role of angiogenesis displaying in tumor development and metastasis has been generally realized. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and endostatin (ES) are critical members of angiogenesis modulating the balance between pro-angiogenenic and anti angiogenenic factors. The aim of this study was to evaluate the circulating level of these factors in serum and explore their prognostic significance in 96 operable non-small cell lung cancer (NSCLC) patients. METHODS: Pre-operational serum VEGF, bFGF, and ES were determined by commercially available enzyme-link immunosorbent assay for 96 NSCLC patients and compared to a cohort of healthy controls (n = 51). Values were correlated with clinicopathological features and overall survival (OS). RESULTS: The pretreatment serum levels of VEGF, bFGF and ES in NSCLC were significantly higher than in the healthy control (P < 0.001, P = 0.009 and P = 0.016, respectively). Univariate survival analysis showed that a high bFGF level correlated with shorter OS and remained an independent factor in multivariate analysis (hazard ratio [HR] = 1.918, 95% confidence interval [CI], 1.061-3.464). In the squamous subtype, a high bFGF indicated a particularly poor prognosis (HR = 2.609, 95% CI, 1.188-5.729). CONCLUSIONS: bFGF is an independent predictor of poor survival in patients with NSCLC. For patients with high serum bFGF, aggressive antitumor treatments should be given after surgery. Approaches targeting the bFGF signaling pathway should be considered as potentially promising therapeutic strategies in NSCLC, especially for the squamous subtype. PMID- 26273401 TI - Effect of inhibition proliferation in human lung adenocarcinoma A549 cells by cytokine-induced killer cells. AB - BACKGROUND: Adenocarcinoma, the most common form of lung cancer, is one of main human malignant tumors. In this paper, we focus on the effect of antitumor activity of cytokine-induced killer (CIK) cells on human lung adenocarcinoma cell line A549. METHODS: CIK cells were obtained by inducing peripheral blood mononuclear cells with recombinant human (rh) interferon-gamma, monoclonal anti CD3 antibody, rh interleukin (IL)-1alpha, and rhIL-2, which were added into the culture. A549 cell viability of CIK cells was determined using MTS assay. Flow cytometry (FCM) experiments were performed to detect cell cycle changes. The expression of P27 in A549 cells treated by CIK cells was evaluated by Western blot. RESULT: The percentage of CD3+CD16+CD56+ T cells in a representative peripheral blood mononucleated cell sample was 33.7 +/- 1.3%. CIK cells, in dose and time dependent manners, inhibited the proliferation of A549. FCM demonstrated that A549 cells were accumulated in G2/M and G0/G1 phases when treated with CIK cells. FCM was used to analyze whether A549 cells treated with CIK cells induced apotosis or necrosis at 10:1 or 20:1. Compared to the control group, P27 was prominently upregulated in the CIK treated group. CONCLUSION: We propose that the pharmacological mechanisms of A549 cells inhibited by CIK cells can be estimated to possibly elicit different biological significance, which, in part, can be ascribed to a different mass transport rate in vitro. PMID- 26273402 TI - Utilization of the International Association for the Study of Lung Cancer and Wang's nodal map for the identification of mediastinum and hilar lymph nodes. AB - BACKGROUND: Transbronchial needle aspiration (TBNA), serving as a remarkably invaluable and minimally invasive technique, has been widely used for the diagnosis and staging of mediastinal adenopathy and masses. To date, the International Association for the Study of Lung Cancer (IASLC) and Wang's nodal map are two well-documented intrathoracic lymph node guidelines for the TBNA procedure. METHOD: We characterized IASLC's and Wang's map, and interpreted the correlation of the two maps station by station. RESULTS: The pivotal role of IASLC map is to determine N descriptor in the tumor node metastasis (TNM) staging system of lung cancer, whilst Wang's map is employed to facilitate the localization of biopsy sites for bronchoscopists during TBNA performance. Furthermore, stations 1, 3 and 5 in Wang' map are equivalent to 4R station in IASLC' system, while stations 4 and 6 in Wang's account for IASLC station 4L as N2 stations. In addition, Wang's stations 2, 8 and 10 are correlated with station 7 in IASLC's. Wang's stations 7 and 9 are responsible for station 11R in IASLC's map. CONCLUSION: Given their unique benefits and limitations, and the practical links between the two maps, it appears reasonable to highlight the significance of their complementary utilization upon TBNA performance and lung cancer staging. PMID- 26273403 TI - Diagnostic value of protein chips constructed by lung-cancer-associated markers selected by the T7 phage display library. AB - BACKGROUND: Traditional diagnostic technology with tumor biomarkers is inefficient, expensive and requires a large number of serum samples. The purpose of this study was to construct human lung cancer protein chips with new lung cancer biomarkers screened by the T7-phage display library, and improve the early diagnosis rate of lung cancer. METHODS: A T7-phage cDNA display library was constructed of fresh samples from 30 lung cancer patients. With biopanning and high-throughput screening, we gained the immunogenic phage clones from the cDNA library. The insert of selected phage was blasted at GeneBank for alignment to find the exact or the most similar known genes. Protein chips were then constructed and used to assay their expression level in lung cancer serum from 217 cases of lung cancer groups:80 cases of benign lung disease and 220 healthy controls. RESULTS: After four rounds of Biopanning and two rounds of enzyme linked immunosorbent assay, 12 phage monoclonal samples were selected from 2880 phage monoclonal samples. After blasting at GeneBank, six similar genes were used to construct diagnostic protein chips. The protein chips were then used to assay expression level in lung cancer serum. The expression level of six genes in lung cancer groups was significantly higher than those in the other two groups (P < 0.05). CONCLUSIONS: In this study, we successfully constructed diagnostic protein chips with biomarkers selected from the lung cancer T7-phage cDNA library, which can be used for the early screening of lung cancer patients. PMID- 26273404 TI - The Prevalence and clinical characteristics of primary Sjogren's syndrome patients with lung cancer: An analysis of ten cases in China and literature review. AB - BACKGROUND: A retrospective analysis of clinical data from primary Sjogren's syndrome (pSS) patients with lung cancer was conducted in order to guide further clinical work. METHODS: From January 1993 to December 2010, 10 pSS patients with lung cancer were hospitalized at the Peking Union Medical College Hospital. One hundred and three pSS patients were recruited as the controls. Patients' clinical data was retrospectively analyzed. RESULT: The incidence rate of lung cancer in pSS patients was 0.477%. The duration from diagnosis of pSS to lung cancer in the 10 patients was 0.92~42 years. The pSS patients with lung cancer were significantly older than those without lung cancer (60.8 +/- 8.9 vs. 44.9 +/- 12.1, P < 0.001). Eight of the pSS patients with lung cancer (80%) were female nonsmokers; five pSS patients with lung cancer (50%) had lung involvement, exhibiting diffuse parenchymal lung disease. Adenocarcinoma was the most common pathological type of lung cancer (90%). Tumor node metastasis staging of lung cancer included: four cases of Ib (40%), one case of IIIb (10%), four cases of IV (40%) and one case undetermined (10%). CONCLUSION: The incidence rate of lung cancer in pSS patients was higher with respect to the normal population. Physicians should closely observe lung cancer incidence during the pSS follow-up period. Adenocarcinoma was the most frequently seen lung cancer pathology in pSS patients. Clinical stages and individualized treatment for pSS patients with lung cancer should be carefully determined. PMID- 26273405 TI - Analysis of lung tumor initiation and progression in transgenic mice for Cre inducible overexpression of Cul4A gene. AB - BACKGROUND: Lung cancer is the leading cause of morbidity and death worldwide. Although the available lung cancer animal models have been informative and further propel our understanding of human lung cancer, they still do not fully recapitulate the complexities of human lung cancer. The pathogenesis of lung cancer remains highly elusive because of its aggressive biologic nature and considerable heterogeneity, compared to other cancers. The association of Cul4A amplification with aggressive tumor growth and poor prognosis has been suggested. Our previous study suggested that Cul4A is oncogenic in vitro, but its oncogenic role in vivo has not been studied. METHODS: Viral delivery approaches have been used extensively to model cancer in mouse models. In our experiments, we used Cre recombinase induced overexpression of the Cul4A gene in transgenic mice to study the role of Cul4A on lung tumor initiation and progression and have developed a new model of lung tumor development in mice harboring a conditionally expressed allele of Cul4A. RESULTS: Here we show that the use of a recombinant adenovirus expressing Cre-recombinase ("AdenoCre") to induce Cul4A overexpression in the lungs of mice allows controls of the timing and multiplicity of tumor initiation. Following our mouse models, we are able to study the potential role of Cul4A in the development and progression in pulmonary adenocarcinoma as well. CONCLUSION: Our findings indicate that Cul4A is oncogenic in vivo, and this mouse model is a tool in understanding the mechanisms of Cul4A in human cancers and for testing experimental therapies targeting Cul4A. PMID- 26273406 TI - Novel link between prostaglandin E2 (PGE2) and cholinergic signaling in lung cancer: The role of c-Jun in PGE2-induced alpha7 nicotinic acetylcholine receptor expression and tumor cell proliferation. AB - BACKGROUND: Cyclooxygenase-2-derived prostaglandin E2 (PGE2) stimulates tumor cell growth and progression. alpha7 nicotinic acetylcholine receptor (nAChR) is a major mediator of cholinergic signaling in tumor cells. In the present study, we investigated the mechanisms by which PGE2 increases non-small cell lung cancer (NSCLC) proliferation via alpha7 nAChR induction. METHODS: The effects of PGE2 on alpha7 nAChR expression, promoter activity, and cell signaling pathways were detected by Western blot analysis, real time reverse transcriptase polymerase chain reaction, and transient transfection assay. The effect of PGE2 on cell growth was determined by cell viability assay. RESULTS: We found that PGE2 induced alpha7 nAChR expression and its promoter activity in NSCLC cells. The stimulatory role of PGE2 on cell proliferation was attenuated by alpha7 nAChR small interfering ribonucleic acids (siRNA) or acetylcholinesterase. PGE2-induced alpha7 nAChR expression was blocked by an antagonist of the PGE2 receptor subtype EP4 and by EP4 siRNA. Furthermore, PGE2 enhanced alpha7 nAChR expression via activation of c-Jun N-terminal kinase (JNK), phosphatidylinositol 3-kinase (PI3 K), and protein kinase A (PKA) pathways followed by increased c-Jun expression, a critical transcription factor. Blockade of c-Jun diminished the effects of PGE2 on alpha7 nAChR promoter activity and protein expression, and cell growth. CONCLUSION: Our results demonstrate that PGE2 promotes NSCLC cell growth through increased alpha7 nAChR expression. This effect is dependent on EP4-mediated activation of JNK, PI3K, and PKA signals that induce c-Jun protein expression and alpha7 nAChR gene promoter activity. Our findings unveil a novel link between prostanoids and cholinergic signaling. PMID- 26273407 TI - Mining featured micro ribonucleic acids associated with lung cancer based on bioinformatics. AB - BACKGROUND: Few genetic markers useful for the screening of lung cancer risk exist. Although related research has shown that certain expression profiles of micro ribonucleic acids (miRNAs) are different in lung cancer versus the normal lung, such as miR-29a and miR-29s, the precise molecular mechanism of lung cancer remains obscure. In order to get a better understanding of the pathogenetic mechanism of lung cancer, we analyzed the differentially expressed genes (DEGs) and identified featured miRNAs in lung cancer tissues. METHODS: We used the gene expression profile GSE10072, including 49 gene chips of non-tumor tissues and 58 gene chips of lung tumor specimens. The DEGs between these two groups were identified by Limma package in R language. The TarBase database was used to construct the networks of miRNA regulating DEGs related to lung cancer. After ordering miRNAs regulating DEGs, we further screened featured miRNAs combined with the miR2Disease database. RESULTS: A total of 5572 DEGs were obtained between lung cancer and control specimens. After constructing a miRNA regulatory network, a total of 398 regulations between 57 miRNAs and 321 target genes existed. By intergrating the miR2Disease database and using a sorting algorithm, a total of six featured miRNAs related to lung cancer were identified, including miR-520h, miR-133a, miR-34, miR-103, miR-370, and miR-148. They might be involved in lung cancer progression by regulating ABCG2, PKM2, VAMP2, GPD1, MAP3K8, and DNMT3B, respectively. CONCLUSION: The top 10 significant miRNAs, such as miR 520h, miR-133a, miR-34, and miR-103 may be potential therapeutic targets for lung cancer. PMID- 26273408 TI - Potential anti-cancer effect of curcumin in human lung squamous cell carcinoma. AB - BACKGROUND: To explore the molecular mechanisms of the anti-cancer effect of curcumin in human lung squamous cell carcinoma (LSQCC) SK-MES-1 cells. METHODS: Cell viability was determined using MTT assay. Ribonucleic acid sequencing was performed to measure expression levels of transcripts in LSQCC cells treated with 15 MUmol/L curcumin (treatment groups) or an equal amount of dimethylsulfoxide (control). Cuffdiff software was used to identify differentially expressed genes (DEGs) in treatment groups, followed by enrichment analysis of DEGs using the Database for Annotation, Visualization and Integration Discovery. The protein protein interaction (PPI) networks for up and downregulated DEGs were constructed by Cytoscape software using Search Tool for the Retrieval of Interacting Genes data to identify hub nodes. RESULTS: Curcumin significantly reduced cell viability in LSQCC cells. In total, 380 DEGs including 154 upregulated and 126 downregulated genes were found in the treatment groups. The upregulated genes were enriched in base excision repair (BER, such as PCNA, POLL, and MUTYH) and Janus kinase-signal transducer and activator of transcription (JAT-STAT) signaling pathways (such as AKT1 and STAT5A), while the downregulated genes were enriched in nine pathways, including the vascular endothelial growth factor (VEGF) signaling pathway (such as PTK2, VEGFA, MAPK1, and MAPK14) and mitogen activated protein kinase (MAPK) signaling pathway (ARRB2, MAPK1, MAPK14, and NFKB1). PCNA and AKT1 were the hub nodes in the PPI network of upregulated genes while MAPK1, MAPK14, VEGFA, and NFKB1 were the hub nodes in the PPI network of downregulated genes. CONCLUSIONS: Curcumin might exert anti-cancer effects on LSQCC via regulating BER, JAT-STAT, VEGF, and MAPK signaling pathways. PMID- 26273409 TI - Diagnostic yield of non-guided flexible bronchoscopy for peripheral pulmonary neoplasia. AB - BACKGROUND: The role of conventional bronchoscopy for peripheral pulmonary neoplasia remains controversial. We aimed to assess the diagnostic yield and the added value of non-guided bronchial aspiration, bronchoalveolar lavage (BAL), and brushing for the diagnosis of pulmonary neoplasia not visible endoscopically. METHODS: We retrospectively assessed 207 consecutive patients with a final diagnosis of peripheral lung malignancy who underwent bronchoscopy with non guided aspiration, brushing, and BAL as their initial evaluation. The influence of clinical and radiological factors on diagnostic yield was assessed using univariate logistic regression analyses. RESULTS: The overall sensitivity of non guided bronchoscopy was 25.6%, whereas sensitivities for bronchial aspiration, BAL, and brushing were 14.2%, 11.6%, and 16.5%, respectively. Younger age, larger lesion, central/intermediate distance from the hilum, presence of a bronchus sign, and higher standardized uptake value (SUV) on positron emission tomography scan were predictors of a higher diagnostic yield. Conversely, forced expiratory volume in one second, fellow implication in the procedure, and tumor histology did not influence sensitivity. The overall sensitivity of bronshoscopy was >40% for tumors >4 cm, located in the central/intermediate thirds of the lung, showing a bronchus sign, with an SUV >12 or occurring in patients <50 years of age. Conversely, the sensitivity was <10% for tumors <2 cm, located peripherally or with an SUV <4. CONCLUSION: Neoplasia characteristics may help targeting situations in which conventional bronchoscopy could be used as the initial diagnostic procedure when advanced techniques are unavailable. However, advanced diagnostic tools should probably be proposed as the initial modality for the diagnosis of peripheral malignant lesions when available. PMID- 26273410 TI - Micro ribonucleic acid-93 promotes proliferation and migration of esophageal squamous cell carcinoma by targeting disabled 2. AB - BACKGROUND: Accumulated evidence has revealed that the dysregulation of micro ribonucleic acids (miRNAs) may contribute to esophageal squamous cell carcinoma (ESCC). MiR-93, which is a member of the miRNA cluster miR-106b~25, has been widely studied for its tumor promoting effect on different types of cancers. However, our knowledge of miR-93 function in ESCC remains unclear. METHODS: The expression levels of miR-93 in ESCC and the adjacent non-tumor tissues were measured by real-time polymerase chain reaction. Cell counting kit-8, flow cytometry, and 5-ethynyl-2'-deoxyuridine incorporation and transwell migration assays were employed to explore the effects of miR-93 on proliferation and migration capabilities in EC109 cells. To determine the possible target gene of miR-93, cell transfection, Western blot analysis and luciferase reporter gene assays were performed. RESULTS: A significant upregulation of miR-93 expression in ESCC tissues was determined, combined with a downregulation of the predicted target gene, disabled 2 (DAB2). The introduction of miR-93 significantly promotes cell proliferation, cell cycle progression, and the metastatic capability of EC109 cells. By cell transfection and luciferase reporter assay, DAB2 was confirmed as a direct target of miR-93. In addition, the knockdown of DAB2 by small interfering RNA displayed a consentaneous phenocopy with miR-93 overexpression in EC109 cells. CONCLUSION: Our results indicate that miR-93 acts as a tumor promoter in ESCC, and its promotion effects on ESCC cell proliferation and migration depend largely upon DAB2 suppression. PMID- 26273411 TI - Circulating PD-L1 in NSCLC patients and the correlation between the level of PD L1 expression and the clinical characteristics. AB - BACKGROUND: The programmed cell death-1/programmed cell death-1 ligand (PD-1/PD L1) pathway plays a crucial role in tumor evasion. This study evaluated the association between circulating PD-L1 expression and clinical characteristics in patients with advanced non-small cell lung cancer (NSCLC). METHODS: A total of 109 advanced NSCLC and 65 healthy patients from the Beijng Cancer Hospital were enrolled in the study. Circulating PD-L1 expression was tested by enzyme-linked immunosorbent assay. The associations between the level of PD-L1 expression and clinicopathologic features and prognosis were statistically analyzed. RESULTS: The expression of PD-L1 in advanced NSCLC patients was significantly upregulated compared with the healthy control (P < 0.001). The expression of PD-L1 was significantly correlated with abdominal organ metastasis (P = 0.004). A high PD L1 expression had a worse prognosis than a low expression in patients (18.7 vs. 26.8 month, P < 0.001). CONCLUSIONS: PD-L1 was elevated in advanced NSCLC patients and may play an important role in tumor immune evasion and patient prognosis. PMID- 26273412 TI - New agent to treat advanced or metastasized thyroid cancer, its efficacy, safety, and mechanism. AB - BACKGROUND: Vandetanib is the first US Food and Drug Administration approved agent to treat advanced or metastasized thyroid cancer. To gain a better understanding of the drug, we conducted a systematic review of its efficacy and safety in patients with thyroid cancers. METHODS: Trial data was retrieved from Pubmed, EMBASE, Medline, China National Knowledge Infrastructure, and the Cochrane database without restrictions on language. A systematic review of the literature was performed to assess median progression-free survival (PFS) and adverse events associated with vandetanib therapy for advanced or metastasized thyroid cancers. RESULTS: Vandetanib statistically prolonged PFS in comparison with the placebo (30.5 vs. 19.3 months, hazard ratio 0.46), It even prolonged PFS in surgically unresectable or metastatic differentiated thyroid cancer cases compared with the placebo (11.1 vs. 5.9 months, hazard ratio 0.63). Rash, diarrhea, neutropenia, and hypertension were the most frequent side effects. CONCLUSION: Vandetanib can significantly improve PFS. Though it has some side effects, it is still a promising agent in the treatment of advanced or metastasized thyroid cancer, especially in those with metastasized or advanced medullary thyroid carcinoma. PMID- 26273413 TI - Four-year natural clinical course of pulmonary epithelioid hemangioendothelioma without therapy. AB - Pulmonary epithelial hemangioendothelioma is a rare low to intermediate malignant vascular tumor originating from vascular endothelial cells. The therapy for this disease, if possible, is surgical resection. However, there is no standard treatment for patients with multiple unresectable lesions. We present the case of a 42-year-old woman treated with a natural clinical course of hemangioendothelioma for four years without therapy. The nodules have increased in number and size extremely slowly, and the patient is alive and asymptomatic four years after diagnosis. PMID- 26273414 TI - Metastases of basal-like breast invasive ductal carcinoma to the endometrium: A case report and review of the literature. AB - We present a case of single endometrial metastasis from breast invasive ductal cancer. This case was unique because the immunohistochemical staining was negative for human epidermal growth factor receptor 2/neu and estrogen and progesterone receptors, and positive for cytokeratin 5/6 and epidermal growth factor receptor in the primary and metastatic tumor cells. No gross evidence of tumor was observed in other sites. We identified 12 cases of metastases to the endometrium from breast carcinoma from series and case reports in the literature between 1985 and 2014. This review indicated that hormone receptor-positive invasive lobular breast cancer cells are more likely to metastasize to the endometrium than other cell types in patients over 50 years of age. PMID- 26273415 TI - Preoperative computed tomography-guided percutaneous localization of ground glass pulmonary opacity with polylactic acid injection. AB - Localization of a ground glass nodule is a difficult challenge for thoracic surgeons, especially for ground glass opacities (GGOs) less than 10 mm in diameter. In this study we implement a new method for preoperative localization of pulmonary (GGOs). From October 2013 to December 2014, computed tomography guided percutaneous polylactic acid injection localizations were performed for five pulmonary nodules in five patients (2 men and 3 women; mean age, 59.8 years; range, 54-65 years). The injection was feasible in all patients and the localization effect was excellent. The total procedure duration was 12.6 minutes (range; 10-15) and the volume of polylactic acid injected was 0.38 mL. The wedge resections were easily and successfully performed in all five cases. The cutting margin was no less than 2 cm from the lesion. This technique is promising for the determination of GGO location in thoracoscopic surgery for wedge resection. PMID- 26273417 TI - In Vitro System for Measuring Chordal Force Changes Following Mitral Valve Patch Repair. AB - BACKGROUND: Attention towards optimization of mitral valve repair methods is increasing. Patch augmentation is one strategy utilized to correct functional mitral regurgitation or systolic anterior motion in complex mitral valve repairs. This article describes a system for investigating the redistribution of chordae tendineae tension as a reflection of altered stress distribution of the valve leaflet following patch augmentation. METHODS AND MATERIALS: An in vitro test setup was constructed to hold native porcine mitral valves containing an annulus and papillary muscle positioning system. The alterations caused by patch augmentation should be visual from both the atrial and ventricular views. Ventricular pressure was regulated stepwise in a range of 0-150 mmHg. To test the system, the anterior mitral leaflet was extended by a pericardial patch sutured to the mid/basal part of the leaflet, and the chordae tendineae force was measured as the ventricular pressure was applied. RESULTS: The system demonstrated the capacity to hold native porcine mitral valves and introducing patch repairs according to clinical practice. The porcine mitral valve test setup indicated strong correlation between the forces in the mitral valve secondary chordae tendineae and the applied transvalvular pressure (R2 = 0.95). CONCLUSION: This test setup proved the ability to obtain normal mid-systolic mitral valve function, secondary chordae force measurements, and important preservation of the visual access: Hence, obtaining the pressure-force relationship as well as identifying any shift of the secondary chordae insertion point on the anterior leaflet relative to the coaptation zone was made possible. PMID- 26273418 TI - Nuclear Nox4 Role in Stemness Power of Human Amniotic Fluid Stem Cells. AB - Human amniotic fluid stem cells (AFSC) are an attractive source for cell therapy due to their multilineage differentiation potential and accessibility advantages. However the clinical application of human stem cells largely depends on their capacity to expand in vitro, since there is an extensive donor-to-donor heterogeneity. Reactive oxygen species (ROS) and cellular oxidative stress are involved in many physiological and pathophysiological processes of stem cells, including pluripotency, proliferation, differentiation, and stress resistance. The mode of action of ROS is also dependent on the localization of their target molecules. Thus, the modifications induced by ROS can be separated depending on the cellular compartments they affect. NAD(P)H oxidase family, particularly Nox4, has been known to produce ROS in the nucleus. In the present study we show that Nox4 nuclear expression (nNox4) depends on the donor and it correlates with the expression of transcription factors involved in stemness regulation, such as Oct4, SSEA-4, and Sox2. Moreover nNox4 is linked with the nuclear localization of redox sensitive transcription factors, as Nrf2 and NF-kappaB, and with the differentiation potential. Taken together, these results suggest that nNox4 regulation may have important effects in stem cell capability through modulation of transcription factors and DNA damage. PMID- 26273419 TI - Controlling Redox Status for Stem Cell Survival, Expansion, and Differentiation. AB - Reactive oxygen species (ROS) have long been considered as pathological agents inducing apoptosis under adverse culture conditions. However, recent findings have challenged this dogma and physiological levels of ROS are now considered as secondary messengers, mediating numerous cellular functions in stem cells. Stem cells represent important tools for tissue engineering, drug screening, and disease modeling. However, the safe use of stem cells for clinical applications still requires culture improvements to obtain functional cells. With the examples of mesenchymal stem cells (MSCs) and pluripotent stem cells (PSCs), this review investigates the roles of ROS in the maintenance of self-renewal, proliferation, and differentiation of stem cells. In addition, this work highlights that the tight control of stem cell microenvironment, including cell organization, and metabolic and mechanical environments, may be an effective approach to regulate endogenous ROS generation. Taken together, this paper indicates the need for better quantification of ROS towards the accurate control of stem cell fate. PMID- 26273421 TI - Isoflavones Reduce Copper with Minimal Impact on Iron In Vitro. AB - Isoflavones are commonly consumed in many Asian countries and have potentially positive effects on human being. Only a few and rather controversial data on their interactions with copper and iron are available to date. 13 structurally related isoflavones were tested in the competitive manner for their Cu/Fe chelating/reducing properties. Notwithstanding the 5-hydroxy-4-keto chelation site was associated with ferric, ferrous, and cupric chelation, the chelation potential of isoflavones was low and no cuprous chelation was observed. None of isoflavones was able to substantially reduce ferric ions, but the vast majority reduced cupric ions. The most important feature for cupric reduction was the presence of an unsubstituted 4'-hydroxyl; contrarily the presence of a free 5 hydroxyl decreased or abolished the reduction due to chelation of cupric ions. The results from this study may enable additional experiments which might clarify the effects of isoflavones on human being and/or mechanisms of copper absorption. PMID- 26273420 TI - Increased Oxidative Stress as a Selective Anticancer Therapy. AB - Reactive oxygen species (ROS) are closely related to tumorgenesis. Under hypoxic environment, increased levels of ROS induce the expression of hypoxia inducible factors (HIFs) in cancer stem cells (CSCs), resulting in the promotion of the upregulation of CSC markers, and the reduction of intracellular ROS level, thus facilitating CSCs survival and proliferation. Although the ROS level is regulated by powerful antioxidant defense mechanisms in cancer cells, it is observed to remain higher than that in normal cells. Cancer cells may be more sensitive than normal cells to the accumulation of ROS; consequently, it is supposed that increased oxidative stress by exogenous ROS generation therapy has an effect on selectively killing cancer cells without affecting normal cells. This paper reviews the mechanisms of redox regulation in CSCs and the pivotal role of ROS in anticancer treatment. PMID- 26273422 TI - Reactive Oxygen Species in Mesenchymal Stem Cell Aging: Implication to Lung Diseases. AB - MSCs have become an emerging cell source with their immune modulation, high proliferation rate, and differentiation potential; indeed, they have been challenged in clinical trials. Recently, it has shown that ROS play a dual role as both deleterious and beneficial species depending on their concentration in MSCs. Various environmental stresses-induced excessive production of ROS triggers cellular senescence and abnormal differentiation on MSCs. Moreover, MSCs have been suggested to participate in the treatment of ALI/ARDS and COPD as a major cause of high morbidity and mortality. Therapeutic mechanisms of MSCs in the treatment of ARDS/COPD were focused on cell engraftment and paracrine action. However, ROS-mediated therapeutic mechanisms of MSCs still remain largely unknown. Here, we review the key factors associated with cell cycle and chromatin remodeling to accelerate or delay the MSC aging process. In addition, the enhanced ROS production and its associated pathophysiological pathways will be discussed along with the MSC senescence process. Furthermore, the present review highlights how the excessive amount of ROS-mediated oxidative stress might interfere with homeostasis of lungs and residual lung cells in the pathogenesis of ALI/ARDS and COPD. PMID- 26273423 TI - Reactive Oxygen Species Are Required for Human Mesenchymal Stem Cells to Initiate Proliferation after the Quiescence Exit. AB - The present study focuses on the involvement of reactive oxygen species (ROS) in the process of mesenchymal stem cells "waking up" and entering the cell cycle after the quiescence. Using human endometrial mesenchymal stem cells (eMSCs), we showed that intracellular basal ROS level is positively correlated with the proliferative status of the cell cultures. Our experiments with the eMSCs synchronized in the G0 phase of the cell cycle revealed a transient increase in the ROS level upon the quiescence exit after stimulation of the cell proliferation. This increase was registered before the eMSC entry to the S-phase of the cell cycle, and elimination of this increase by antioxidants (N-acetyl-L cysteine, Tempol, and Resveratrol) blocked G1-S-phase transition. Similarly, a cell cycle arrest which resulted from the antioxidant treatment was observed in the experiments with synchronized human mesenchymal stem cells derived from the adipose tissue. Thus, we showed that physiologically relevant level of ROS is required for the initiation of human mesenchymal stem cell proliferation and that low levels of ROS due to the antioxidant treatment can block the stem cell self renewal. PMID- 26273425 TI - GC-Rich Extracellular DNA Induces Oxidative Stress, Double-Strand DNA Breaks, and DNA Damage Response in Human Adipose-Derived Mesenchymal Stem Cells. AB - BACKGROUND: Cell free DNA (cfDNA) circulates throughout the bloodstream of both healthy people and patients with various diseases. CfDNA is substantially enriched in its GC-content as compared with human genomic DNA. PRINCIPAL FINDINGS: Exposure of haMSCs to GC-DNA induces short-term oxidative stress (determined with H2DCFH-DA) and results in both single- and double-strand DNA breaks (comet assay and gammaH2AX, foci). As a result in the cells significantly increases the expression of repair genes (BRCA1 (RT-PCR), PCNA (FACS)) and antiapoptotic genes (BCL2 (RT-PCR and FACS), BCL2A1, BCL2L1, BIRC3, and BIRC2 (RT PCR)). Under the action of GC-DNA the potential of mitochondria was increased. Here we show that GC-rich extracellular DNA stimulates adipocyte differentiation of human adipose-derived mesenchymal stem cells (haMSCs). Exposure to GC-DNA leads to an increase in the level of RNAPPARG2 and LPL (RT-PCR), in the level of fatty acid binding protein FABP4 (FACS analysis) and in the level of fat (Oil Red O). CONCLUSIONS: GC-rich fragments in the pool of cfDNA can potentially induce oxidative stress and DNA damage response and affect the direction of mesenchymal stem cells differentiation in human adipose-derived mesenchymal stem cells. Such a response may be one of the causes of obesity or osteoporosis. PMID- 26273426 TI - Upregulation of Multidrug Resistance-Associated Protein 1 by Allyl Isothiocyanate in Human Bronchial Epithelial Cell: Involvement of c-Jun N-Terminal Kinase Signaling Pathway. AB - Multidrug resistance-associated protein 1 (MRP1) plays a protective role in the etiology and progression of chronic obstructive pulmonary disease (COPD) which results from oxidative stress and inflammation of lung injury. The lower functional MRP1 activity is related to COPD development. Our previous study showed that Allyl isothiocyanate (AITC) induced the expression and activity of MRP1 in a dose-dependent manner. However, which signaling pathway contributes to the upregulation of MRP1 by AITC is unclear. In this study, signaling pathway specific inhibitors were used to examine the mechanism of AITC. We found that JNK inhibitor SP600125 treatment decreased MRP1 mRNA expression in 16HBE14o- cells. But the ERK inhibitor U0126 or PI3K/Akt inhibitor LY294002 produced no obvious effect. The AITC-induced increase of MRP1 mRNA expression was abolished by cotreatment of SP600125, while it was not obviously affected by U0126 or LY294002. Furthermore, AITC acivates the JNK signaling pathway in 16HBE14o- cells. Finally, we found that JNK pathway mediated the upregulation of AITC induced expression and function of MRP1. Taken together, our results indicated that AITC increased the expression and the activity of MRP1 via a JNK-dependent pathway. ERK and PI3K signaling pathway were not involved in the expression of MRP1 mRNA. PMID- 26273424 TI - Redox Regulation in Cancer Stem Cells. AB - Reactive oxygen species (ROS) and ROS-dependent (redox regulation) signaling pathways and transcriptional activities are thought to be critical in stem cell self-renewal and differentiation during growth and organogenesis. Aberrant ROS burst and dysregulation of those ROS-dependent cellular processes are strongly associated with human diseases including many cancers. ROS levels are elevated in cancer cells partially due to their higher metabolism rate. In the past 15 years, the concept of cancer stem cells (CSCs) has been gaining ground as the subpopulation of cancer cells with stem cell-like properties and characteristics have been identified in various cancers. CSCs possess low levels of ROS and are responsible for cancer recurrence after chemotherapy or radiotherapy. Unfortunately, how CSCs control ROS production and scavenging and how ROS dependent signaling pathways contribute to CSCs function remain poorly understood. This review focuses on the role of redox balance, especially in ROS dependent cellular processes in cancer stem cells (CSCs). We updated recent advances in our understanding of ROS generation and elimination in CSCs and their effects on CSC self-renewal and differentiation through modulating signaling pathways and transcriptional activities. The review concludes that targeting CSCs by manipulating ROS metabolism/dependent pathways may be an effective approach for improving cancer treatment. PMID- 26273427 TI - Ethnic Identity as a Moderator against Discrimination for Transracially and Transnationally Adopted Korean American Adolescents. AB - Despite the growing practice of international adoption over the past 60 years, the racial and ethnic experiences of adopted youth are not well known. This study examined the moderating role of ethnic identity in the association between racial/ethnic discrimination and adjustment among transracially, transnationally adopted Korean American adolescents (N = 136). Building on self-categorization theory and past empirical research on Asian Americans, it was hypothesized that ethnic identity would exacerbate negative outcomes associated with discrimination. The moderating role of ethnic identity was found to vary by specific ethnic identity dimensions. For individuals with more pride in their ethnic group (affective dimension of ethnic identity), discrimination was positively associated with externalizing problems. For individuals with greater engagement with their ethnic group (behavioral dimension of ethnic identity), discrimination was positively associated with substance use. By contrast, clarity regarding the meaning and importance of one's ethnic group (cognitive dimension of ethnic identity) did not moderate the relationship between discrimination and negative outcomes. PMID- 26273428 TI - Hypomethylation of miR-142 promoter and upregulation of microRNAs that target the oxytocin receptor gene in the autism prefrontal cortex. AB - BACKGROUND: MicroRNAs are small RNA molecules that regulate the translation of protein from gene transcripts and are a powerful mechanism to regulate gene networks. Next-generation sequencing technologies have produced important insights into gene transcription changes that occur in the brain of individuals diagnosed with autism spectrum disorder (asd). However, these technologies have not yet been employed to uncover changes in microRNAs in the brain of individuals diagnosed with asd. METHODS: Small RNA next-generation sequencing was performed on RNA extracted from 12 human autism brain samples and 12 controls. Real-time PCR was used to validate a sample of the differentially expressed microRNAs, and bioinformatic analysis determined common pathways of gene targets. MicroRNA expression data was correlated to genome-wide DNA methylation data to determine if there is epigenetic regulation of dysregulated microRNAs in the autism brain. Luciferase assays, real-time PCR, and Western blot analysis were used to determine how dysregulated microRNAs may regulate the expression and translation of an autism-related gene transcript. RESULTS: We determined that miR-142-5p, miR 142-3p, miR-451a, miR-144-3p, and miR-21-5p are overexpressed in the asd brain. Furthermore, the promoter region of the miR-142 gene is hypomethylated in the same brain samples, suggesting that epigenetics plays a role in dysregulation of microRNAs in the brain. Bioinformatic analysis revealed that these microRNAs target genes that are involved in synaptic function. Further bioinformatic analysis, coupled with in vitro luciferase assays, determined that miR-451a and miR-21-5p can target the oxytocin receptor (OXTR) gene. OXTR gene expression is increased in these same brain samples, and there is a positive correlation between miR-21-5p and OXTR expression. However, miR-21-5p expression negatively correlates to production of OXTR protein from the OXTR transcript. Therefore, we suggest that miR-21-5p may attenuate OXTR expression in the human autism brain. CONCLUSIONS: Our data suggests that dysregulation of microRNAs may play a biological role in the brain of individuals of autism. In addition, we suggest an interaction between epigenetic mechanisms and microRNA dysregulation in the brain. Overall, this data adds an important link in our understanding of the molecular events that are dysregulated in the brain of individuals diagnosed with autism. PMID- 26273429 TI - Senescent mesenchymal stem cells promote colorectal cancer cells growth via galectin-3 expression. AB - BACKGROUND: Cellular senescence is linked to aging and tumorigenesis. The senescence of mesenchymal stem cells (MSCs) may influence the tumor growth, metastasis, and angiogenesis by secreting a variety of cytokines and growth factors. RESULTS: The conditioned media of adipose derived MSCs (AD-MSCs) stimulated the proliferation of human LoVo colorectal-cancer cells, and the replicative senescent MSCs had the more obvious effects in comparison to that of premature AD-MSCs. Analysis of the factors secreted in the MSCs culture media determined that senescent MSCs expressed and secreted high levels of galectin-3. Galectin-3 expression correlated with the stimulatory effect of senescent AD-MSCs on LoVo cells proliferation, as knockdown of galectin-3 in senescent AD-MSCs significantly reversed the effect of MSCs-mediated growth stimulation of LoVo cells. Furthermore, the simultaneous addition of recombinant galectin-3 to the co culture systems partially restored the tumor-promoting effect of the senescent AD MSCs. Analysis of the mechanisms of senescent MSCs and galectin-3 on LoVo cells signal transduction determined that senescent MSCs and exogenous galectin-3 promoted cell growth by activating the mitogen-activated protein kinase (MAPK) (extracellular signal-regulated kinase [ERK]1/2) pathway. CONCLUSIONS: Senescent MSCs may alter the tissue microenvironment and affect nearby malignant cells via cytokine secretion, and galectin-3 is an important mediator of senescent AD-MSC mediated stimulation of colon cancer cell growth. Therefore, thorough assessment of AD-MSCs prior to their implementation in clinical practice is warranted. PMID- 26273430 TI - Comparing the Bbs10 complete knockout phenotype with a specific renal epithelial knockout one highlights the link between renal defects and systemic inactivation in mice. AB - BACKGROUND: Bardet-Biedl Syndrome (BBS) is a genetically heterogeneous ciliopathy with clinical cardinal features including retinal degeneration, obesity and renal dysfunction. To date, 20 BBS genes have been identified with BBS10 being a major BBS gene found to be mutated in almost 20 percent of all BBS patients worldwide. It codes for the BBS10 protein which forms part of a chaperone complex localized at the basal body of the primary cilium. Renal dysfunction in BBS patients is one of the major causes of morbidity in human patients and is associated initially with urinary concentration defects related to water reabsorption impairment in renal epithelial cells. The aim of this study was to study and compare the impact of a total Bbs10 inactivation (Bbs10 (-/-)) with that of a specific renal epithelial cells inactivation (Bbs10 (fl/fl) ; Cdh16-Cre (+/-)). RESULTS: We generated the Bbs10 (-/-) and Bbs10 (fl/fl) ; Cadh16-Cre (+/-) mouse model and characterized them. Bbs10 (-/-) mice developed obesity, retinal degeneration, structural defects in the glomeruli, polyuria associated with high circulating arginine vasopressin (AVP) concentrations, and vacuolated, yet ciliated, renal epithelial cells. On the other hand, the Bbs10 (fl/fl) ; Cadh16-Cre (+/-)mice displayed no detectable impairment. CONCLUSIONS: These data highlight the importance of a systemic Bbs10 inactivation to trigger averted renal dysfunction whereas a targeted absence of BBS10 in the renal epithelium is seemingly non deleterious. PMID- 26273433 TI - Coagulopathy and functional hyposplenism during an episode of thrombotic thrombocytopenic purpura in a HgbS/beta (+)-thalassemia patient. AB - We report a case of TTP in a sickle cell/beta+-thalassemia heterozygote with nonspecific complaints and a evidence of hemolysis, initially attributed to sickle crisis. Included in this case is a discussion of the development of functional hyposplenism, a rarely reported complication, limitation of ADAMTS-13 in diagnosis, and the use of platelet transfusion. PMID- 26273434 TI - Recurrent undifferentiated shock: Idiopathic Systemic Capillary Leak Syndrome. AB - Idiopathic Systemic Capillary Leak Syndrome is a potentially fatal disorder that is under diagnosed. It commonly presents as recurrent undifferentiated shock with hypotension, hypoalbuminemia and hemoconcentration. There are three distinct phases that define the syndrome; Prodromal, Extravasation and Recovery. PMID- 26273431 TI - Reliability of a new test battery for fitness assessment of the European Astronaut corps. AB - BACKGROUND: To optimise health for space missions, European astronauts follow specific conditioning programs before, during and after their flights. To evaluate the effectiveness of these programs, the European Space Agency conducts an Astronaut Fitness Assessment (AFA), but the test-retest reliability of elements within it remains unexamined. The reliability study described here presents a scientific basis for implementing the AFA, but also highlights challenges faced by operational teams supporting humans in such unique environments, especially with respect to health and fitness monitoring of crew members travelling not only into space, but also across the world. The AFA tests assessed parameters known to be affected by prolonged exposure to microgravity: aerobic capacity (VO2max), muscular strength (one repetition max, 1 RM) and power (vertical jumps), core stability, flexibility and balance. Intraclass correlation coefficients (ICC3.1), standard error of measurement and coefficient of variation were used to assess relative and absolute test-retest reliability. RESULTS: Squat and bench 1 RM (ICC3.1 = 0.94-0.99), hip flexion (ICC3.1 = 0.99) and left and right handgrip strength (ICC3.1 = 0.95 and 0.97), showed the highest test-retest reliability, followed by VO2max (ICC3.1 = 0.91), core strength (ICC3.1 = 0.78 0.89), hip extension (ICC3.1 = 0.63), the countermeasure (ICC3.1 = 0.76) and squat (ICC3.1 = 0.63) jumps, and single right- and left-leg jump height (ICC3.1 = 0.51 and 0.14). For balance, relative reliability ranged from ICC3.1 = 0.78 for path length (two legs, head tilted back, eyes open) to ICC3.1 = 0.04 for average rotation velocity (one leg, eyes closed). CONCLUSIONS: In a small sample (n = 8) of young, healthy individuals, the AFA battery of tests demonstrated acceptable test-retest reliability for most parameters except some balance and single-leg jump tasks. These findings suggest that, for the application with astronauts, most AFA tests appear appropriate to be maintained in the test battery, but that some elements may be unreliable, and require either modification (duration, selection of task) or removal (single-leg jump, balance test on sphere) from the battery. The test battery is mobile and universally applicable for occupational and general fitness assessment by its comprehensive composition of tests covering many systems involved in whole body movement. PMID- 26273435 TI - Age-related Epstein-Barr virus-positive mucocutaneous ulcer: a case report. AB - Key Clinical Message The oral manifestations of EBV-positive mucocutaneous ulcers have a worrisome clinical appearance but relatively benign clinical course, responding well to conservative treatment. Elderly patients who develop an unexplained, persistent ulcer of the oral mucosa should have the lesion examined for EBV. PMID- 26273432 TI - Lysozyme as an alternative to growth promoting antibiotics in swine production. AB - Lysozyme is a naturally occurring enzyme found in bodily secretions such as tears, saliva, and milk. It functions as an antimicrobial agent by cleaving the peptidoglycan component of bacterial cell walls, which leads to cell death. Antibiotics are also antimicrobials and have been fed at subtherapeutic levels to swine as growth promoters. These compounds benefit swine producers by minimizing production losses by increasing feed efficiency and decreasing susceptibility to bacterial infection and disease. This manuscript reviews the knowledge of the effects of lysozyme, as compared to traditional subtherapeutic antibiotics in swine feed, on pig performance and health. It is clear from decades of studies that antibiotic use in feeds increases pig performance, particularly in the nursery. Similarly, lysozyme, as a feed additive, increases growth and feed efficiency. While the mechanism by which antibiotics and lysozyme improve performance is not clearly understood, both of these feed additives improve gastrointestinal health, improve the metabolic profile, and alter the gastrointestinal bacteria ecology of swine. Therefore, lysozyme is a suitable alternative to growth-promoting subtherapeutic antibiotic use in swine feed. PMID- 26273436 TI - Infantile pyknocytosis, a rare cause of hemolytic anemia in newborns: report of two cases in twin girls and literature overview. AB - Infantile pyknocytosis is a rare cause of neonatal jaundice and hemolytic anemia. We report on two cases in twin girls that were diagnosed on peripheral blood smear reading. Pyknocytosis should be considered in cases of early unexplained severe hemolytic anemia, and systematic peripheral smear review performed. Its management consists of phototherapy and RBC transfusion. PMID- 26273437 TI - Necrobiosis lipoidica associated with Hashimoto's thyroiditis and positive detection of ANA and ASMA autoantibodies. AB - Necrobiosis lipoidica (NL) is a rare idiopathic cutaneous condition exceptionally associated with autoimmune thyroiditis. We describe the first case of NL, Hashimoto's thyroiditis and positive detection of autoantibodies. Appropriate screening for NL in patients with autoimmune thyroiditis may clarify its real incidence and the existence of a common pathogenetic pathway. PMID- 26273438 TI - A case report of Progressive subluxation leading to an anterior dislocation of the hip following sliding hip screw fixation for pertrochanteric Extracapsular 4 part fracture neck of femur. AB - Unstable 4 part pertrochanteric fractures without lateral cortical support presents considerable technical problem in treatment with high risk of failure with any implant. Anatomical or slight valgus reduction and subchondral central position of the lag screw (TAD <25 mm) reduces the chance of screw cut out and other complications. PMID- 26273439 TI - Management for traumatic chronic subdural hematoma patients with well-controlled shunt system for hydrocephalus. AB - Traumatic CSDH enlarged in two cases with VP or LP shunt system although the shunt valve pressure was increased to 200 mmH2O. In surgery, the hematoma cavity pressure was found to be 130 and 140 mmH2O, suggesting that to raise the shunt valve pressure is not effective for decreasing CSDH volume. PMID- 26273440 TI - A case of myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) successfully treated with lenalidomide. AB - Lenalidomide is an immunomodulatory drug which is used to treat patients with MDS with deletion 5q chromosomal abnormality. In 2008, WHO introduced a new disease entity called MDS/MPN. No specific treatment for MDS/MPN subtype has yet been identified. We report a patient with MDS/MPN who responded well to lenalidomide therapy. PMID- 26273441 TI - Paradoxical increase in blood pressure following bilateral native nephrectomy. AB - Hypertension with Chronic kidney disease is often difficult to control medically. In such patients, nephrectomy can help to control blood pressure (BP). We describe a case of a 6-year-old boy with autosomal recessive polycystic kidney disease who showed a paradoxical increase in BP following bilateral nephrectomy. PMID- 26273442 TI - Is STEP the future for patients requiring proctocolectomy? A new therapeutic proposal from pediatric experience. AB - We present a pediatric case of medically unmanageable juvenile colonic polyposis, initially treated with subtotal colectomy and an ileostomy followed by a proctectomy, ileal-J-pouch and serial transverse enteroplasties (STEP) of the distal ileum. The STEP procedure in an adequate length was able to control stooling of our patient. PMID- 26273443 TI - Gastric Schwannoma: Case report from Tanzania and brief review of literature. AB - Upper gastrointestinal bleeding causes significant morbidity and mortality worldwide. We report a rare case of hematemesis secondary to a gastric schwannoma in a Tanzanian female. Gastric schwannomas should be considered in the differential diagnosis of gastric masses and distinguished from other etiologies, given their excellent postresection prognosis. PMID- 26273444 TI - A multifaceted approach to calcium channel blocker overdose: a case report and literature review. AB - Calcium channel blocker toxicity can be devastating. Initial therapy with fluid, calcium, and adrenoreceptor agonists should be prompt and novel therapies can be added if no response. Determining cardiogenic shock versus vasoplegia with echocardiogram or other hemodynamic monitoring may guide treatment options. PMID- 26273445 TI - Genomic characterization of chromosome 8 pericentric trisomy. AB - We present a patient with trisomy 8p11.21q11.21 associated with language, gross motor, fine motor, and cognitive delay. Furthermore, using array-based comparative genomic hybridization, we identify the specific genes duplicated in our patient. PMID- 26273446 TI - Synchronous adenomyomas of the ileum in an adult-an exceptional cause of intussusception. AB - In this article, we report a case of two synchronous ileal adenomyomas leading to intussusception. This rare occurrence has never been reported in the literature. Our case is noteworthy, because the lesion is rare and should be considered in the differential diagnosis of intussusception in adults. PMID- 26273447 TI - Bilateral femur metastases in low-grade endometrial carcinoma. AB - Lower-limb bone metastases are uncommon in low-grade endometrial carcinoma, and are mostly located on the axial skeleton. Here, we present a rare case of bilateral femur metastases in low-grade endometrial carcinoma and performed a review of the current literature. PMID- 26273448 TI - Successful treatment of a noninhibitory antibody-mediated acquired factor X deficiency in a patient with marginal-zone lymphoma. AB - Prolonged clotting times were observed in a patient with spontaneous hemorrhage. Analysis showed severe factor X deficiency due to clearance by a noninhibitory antibody. Lymphadenopathy identified on imaging led to diagnosis of marginal B cell lymphoma. Treatment of lymphoma with rituximab and chlorambucil resulted in complete disappearance of the bleeding disorder. PMID- 26273449 TI - Isolated deep T-wave inversion on an electrocardiogram with normal wall motion. AB - The electrocardiogram (ECG) of a 73-year-old, asymptomatic woman showed deep T wave inversion. The complete workup was negative. Ten years later, she developed takotsubo cardiomyopathy with abnormal ECG again. Isolated deep T-wave inversion might be an aftereffect of takotsubo cardiomyopathy that does not warrant an invasive workup. PMID- 26273450 TI - Regenerative therapy for the management of a large skin wound in a dog. AB - Extensive full-thickness skin wounds are quite common in domestic animals. In these report, following the failure of reconstructive surgery, adipose tissue derived mesenchymal stem cells, and platelet-rich plasma were successfully used in a dog to improve speed and quality of skin tissue healing, avoiding suffering, and debilitating effects. PMID- 26273451 TI - Nonsyndromic X-linked intellectual deficiency in three brothers with a novel MED12 missense mutation [c.5922G>T (p.Glu1974His)]. AB - X-linked intellectual deficiency (XLID) is a large group of genetic disorders. MED12 gene causes syndromic and nonsyndromic forms of XLID. Only seven pathological mutations have been identified in this gene. Here, we report a novel mutation segregating with XLID phenotype. This mutation could be in favor of genotype-phenotype correlations. PMID- 26273452 TI - Sandwich osteotomy of the atrophic posterior mandible prior to implant placement. AB - Key Clinical Message The continuing resorption of the alveolar ridge will eventually result in insufficient bone height superior to the IAN, making dental implant placement impossible. The augmentation procedure above the IAN in terms of height provides sufficient bone for implant placement and allows long-term successful restoration of missing teeth with implant-supported prosthesis. PMID- 26273453 TI - Ibrutinib and rituximab induced rapid response in refractory Richter syndrome. AB - We report a 53-year-old man diagnosed with Richter syndrome. He was heavily pretreated and was refractory to prior therapy. He received rituximab and ibrutinib, and achieved a significant response after 1 month of therapy. Our case illustrates the importance of investigation of rituximab and ibrutinib in Richter's syndrome. PMID- 26273454 TI - Immunogenicity of pneumococcal vaccination in a patient with sickle hemoglobinopathy: a case report. AB - Despite decrease in morbidity and mortality from invasive pneumococcal disease (IPD), individuals with asplenia remain at risk for IPD compared to the general population. This report describes a young adult with hemoglobin SD and documented splenic autoinfarction with pneumococcal sepsis, meningitis, and pneumonia within seven months of immunization with PPSV-23. PMID- 26273455 TI - A case of Manila type Mycobacterium tuberculosis infection in Japan. AB - A 76-year-old Japanese woman contracted a Mycobacterium tuberculosis (TB, Manila type) infection in Japan, despite never having traveled. However, her son was treated for TB in the Philippines 3 years before he stayed at her house. Spoligotyping allows us to identify the TB genotype and identify the route of infection. PMID- 26273456 TI - Pulmonary amyloidosis mimicking prostate cancer metastasis. AB - Localized nodular pulmonary amyloidosis is rare. However, the disease should be considered in the differential diagnosis of multiple lung nodules. PMID- 26273457 TI - Acute kidney injury due to abdominal compartment syndrome caused by duodenal metastases of prostate cancer. AB - Organ dysfunctions caused by intraabdominal hypertension is named as abdominal compartment syndrome (ACS). A patient with prostate cancer admitted with dyspnea and oliguria. After decompression his health status improved. For patients with malignant disorders presented with oliguria and respiratory problems who have abdominal distension, ACS should be in mind. PMID- 26273458 TI - Human embryonic stem cells (hESCs) in the treatment of emphysematous COPD: a case report. AB - Emphysema results in narrowing of the small airways due to inhaling of cigarette smoke and other noxious particles. Oxygen therapy, corticosteroids, and bronchodilators increase the risk of pneumonia, arrhythmia, and fractures in long term. Therapy with human embryonic stem cells resulted in improved symptoms of a patient with emphysema. PMID- 26273459 TI - Low-dose niacin supplementation modulates GPR109A, niacin index and ameliorates Parkinson's disease symptoms without side effects. AB - A 65-year-old male, Parkinson's disease patient, was evaluated for GPR109A expression, niacin index, UPDRS scale, handwriting test, and quality of sleep with and without niacin treatment. The evaluation was repeated 3 months after niacin was stopped. Niacin modulated the abovementioned parameters and showed the overall improvement without side effects. PMID- 26273460 TI - Iliopsoas abscess in adolescents with type 1 diabetes mellitus. AB - Iliopsoas abscesses have been reported in adult diabetic patients, but only one case has been so far reported in the pediatric diabetic literature. We report three cases of iliopsoas abscesses in three adolescents with type 1 diabetes mellitus, suggesting that an increased awareness of this condition is required for its early recognition and prompt treatment. PMID- 26273461 TI - Prenatal diagnosis of X-linked adrenoleukodystrophy associated with isolated pericardial effusion. AB - This is the first reported case of fetal pericardial effusion in association with X-linked adrenoleukodystrophy and hypocortisolism from a nonautoimmune cause. Our hypothesis is that in experienced hands and after accurate genetic counseling, isolated pericardial effusion can constitute an indication for a severe metabolic disease. PMID- 26273462 TI - Brentuximab vedotin in the treatment of a patient with refractory Hodgkin disease and Proteus syndrome - a case report and discussion. AB - Treatment of patients with refractory Hodgkin lymphoma is a significant issue. We report a patient with Proteus syndrome and relapsed Hodgkin lymphoma, whose remission was finally achieved after brentuximab vedotin therapy, allowing her to receive a haploidentical stem cell transplant. The possible relationship between both disorders was discussed. PMID- 26273463 TI - Severe fludarabine neurotoxicity after reduced intensity conditioning regimen to allogeneic hematopoietic stem cell transplantation: a case report. AB - We present a case of severe, irreversible neurotoxicity in a 55-year-old-patient with myelofibrosis undergoing hematopoietic stem cell transplantation following a reduced intensity conditioning including fludarabine. The patient developed progressive sensory-motor, visual and consciousness disturbances, eventually leading to death. MRI imaging pattern was unique and attributable to fludarabine neurotoxicity. PMID- 26273464 TI - Convulsion and cerebellar ataxia associated with maternally inherited diabetes and deafness: a case report. AB - Convulsion in diabetics is often considered as a result from fluctuation of blood glucose level. However, if a diabetic patient also presents abnormal neurological signs, mitochondrial diseases need to be considered in the differential diagnosis. PMID- 26273465 TI - A case of delayed hemothorax with an inferior phrenic artery injury detected and treated endovascularly. AB - We report the rare case of delayed hemothorax (DHX) with an inferior phrenic artery (IPA) injury due to blunt thoracic trauma. Our case suggests that DHX almost always occurs early after injury, and endovascular treatment is an effective procedure for traumatic hemothorax including DHX. PMID- 26273466 TI - Association of long-term tacrolimus (FK506) therapy with abnormal megakaryocytosis, bone marrow fibrosis, and dyserythropoiesis. AB - Haematopoietic abnormalities associated with tacrolimus are relatively rare with reversible pure red cell aplasia being the most common. We report for the first time, to our best knowledge, tacrolimus therapy associated with bone marrow fibrosis, abnormal megakaryocytosis, and dyserythopoiesis in a 17-year-old male treated with tacrolimus for nephrotic syndrome. PMID- 26273468 TI - Therapeutic application of C1 esterase inhibitor concentrate for clinical amniotic fluid embolism: a case report. AB - We present the successful application of C1 esterase inhibitor (C1INH) concentrate to a patient with clinical amniotic fluid embolism (AFE). PMID- 26273469 TI - Unilateral foveal hypoplasia in a child with bilateral anterior segment dysgenesis. AB - In patients with foveal hypoplasia, anterior segment dysgenesis and an absence of systemic findings, consider a recently described syndrome of foveal hypoplasia, optic nerve decussation defects and anterior segment dysgenesis (FHONDA) in the differential diagnosis. PMID- 26273467 TI - Atypical manifestation of cat-scratch disease: isolated epigastric pain in an immunocompetent, 12-year-old child. AB - We present a 12-year-old immunocompetent girl with hepato splenic cat-scratch disease (CSD). Her sole inaugural complaint was isolated epigastric pain. She fully recovered, with normalized abdominal CT scan following 2 weeks course of Azythromycin(r). CSD should be included in differential diagnosis in children with epigastric pain, especially in those with domestic pets. PMID- 26273470 TI - Snapshot quiz - "Tattoo of Scheepers". AB - An ink marker at the descending part of the gastrojejunostomy or duodenojejunostomy after a pancreaticoduodenectomy or pylorus-preserving pancreaticoduodenectomy prevents a misplacing of a postoperative endoscopic intervention. PMID- 26273473 TI - The importance of IgG4 in the predictive model of thyroiditis. AB - Immunoglobulin (Ig)G4-related sclerosing disease (IgG4-RSD) is a new disease entity first proposed with regard to autoimmune pancreatitis. A 67-year-old male patient was examined because of weight loss and an abdominal pain. Based on the clinical characteristics, laboratory parameters and ultrasound features, we identified the diagnosis of the IgG4-related systemic disease (IgG4-RSD), that was confirmed by the histopathological analysis after the biopsy of the head of pancreas. After confirmation, we started with the corticosteroid therapy with a good clinical, biochemical and morphological response. During the previous therapy, the disturbance of glucoregulation appeared, so we had to change the modality of treatment. We decided to add Azathioprine to the therapy in a dose of 150 mg/day. We achieved a stable phase of the disease with IgG 4.37 g/l and IgG4 0.179 g/l, and with no side effects from the therapy. LEARNING POINTS: There are potential clinical applications of identifying subsets of patients with IgG4 thyroiditis (FVHT and Riedel thyroiditis).A trial of immunosuppressive therapy should be included if a resection is deemed inadvisable.In particular, cases of FVHT that mimic malignancy, tissue and serum IgG4 may provide supportive diagnostic information. PMID- 26273474 TI - Neurofibromatosis-related phaeochromocytoma: two cases with large tumours and elevated plasma methoxytyramine. AB - We present two cases of adrenal phaeochromocytoma in patients with a previous diagnosis of neurofibromatosis type 1 (NF1). One had an adrenergic phenotype. The other had a more noradrenergic phenotype. Both had large primary tumours, which increases the likelihood of malignancy. Both also had elevated plasma-free methoxytyramine, which has been linked with malignancy even in non-SDHB phaeochromocytomas. LEARNING POINTS: Phaeochromocytoma can have varied clinical presentations.Methoxytyramine can be useful in the biochemical work-up of both SDHB-positive and SDHB-negative phaeochromocytoma.The utility of methoxytyramine as a marker of malignancy in NF1-related phaeochromocytoma is unclear, and cases with elevated titres warrant longer follow-up. PMID- 26273472 TI - Study protocol of a multicenter randomized controlled trial comparing the effectiveness of group and individual internet-based Mindfulness-Based Cognitive Therapy with treatment as usual in reducing psychological distress in cancer patients: the BeMind study. AB - BACKGROUND: Mindfulness-based interventions have shown to reduce psychological distress in cancer patients. The accessibility of mindfulness-based interventions for cancer patients could be further improved by providing mindfulness using an individual internet-based format. The aim of this study is to test the effectiveness of a Mindfulness-Based Cognitive Therapy (MBCT) group intervention for cancer patients in comparison with individual internet-based MBCT and treatment as usual (TAU). METHODS/DESIGN: A three-armed multicenter randomized controlled trial comparing group-based MBCT to individual internet-based MBCT and TAU in cancer patients who suffer from at least mild psychological distress (Hospital Anxiety and Depression Scale (HADS) >= 11). Measurements will be conducted prior to randomization (baseline), post-treatment and at 3 months and 9 months post-treatment. Participants initially allocated to TAU are subsequently randomized to either group- or individual internet-based MBCT and will receive a second baseline measurement after 3 months. Thus, the three-armed comparison will have a time span of approximately 3 months. The two-armed intervention comparison includes a 9-month follow-up and will also consist of participants randomized to the intervention after TAU. Primary outcome will be post-treatment psychological distress (HADS). Secondary outcomes are fear of cancer recurrence (Fear of Cancer Recurrence Inventory), rumination (Rumination and Reflection Questionnaire), positive mental health (Mental Health Continuum - Short Form), and cost effectiveness (health-related quality of life (EuroQol -5D and Short Form-12) and health care usage (Trimbos and iMTA questionnaire on Costs associated with Psychiatric illness). Potential predictors: DSM-IV-TR mood/anxiety disorders (SCID-I) and neuroticism (NEO-Five Factor Inventory) will be measured. Mediators of treatment effect: mindfulness skills, (Five-Facets of Mindfulness Questionnaire- Short Form), working alliance (Working Alliance Inventory) and group cohesion (Group Cohesion Questionnaire) will also be measured. DISCUSSION: This trial will provide valuable information on the clinical and cost effectiveness of group versus internet-based MBCT versus TAU for distressed cancer patients. TRIAL REGISTRATION: Clinicaltrials.gov NCT02138513. Registered 6 May 2014. PMID- 26273475 TI - Pure aldosterone-secreting adrenocortical carcinoma in a patient with refractory primary hyperaldosteronism. AB - We describe a young male patient with longstanding hypertension, who was diagnosed with primary hyperaldosteronism and treated by an attempted retroperitoneoscopic total unilateral adrenalectomy for a left-sided presumed aldosterone-secreting adenoma. Imaging had shown an unremarkable focal adrenal lesion with normal contralateral adrenal morphology, and histology of the resected specimen showed no adverse features. Post-operatively, his blood pressure and serum aldosterone levels fell to the normal range, but 9 months later, his hypertension recurred, primary aldosteronism was again confirmed and he was referred to our centre. Repeat imaging demonstrated an irregular left sided adrenal lesion with normal contralateral gland appearances. Adrenal venous sampling was performed, which supported unilateral (left-sided) aldosterone hypersecretion. Redo surgery via a laparoscopically assisted transperitoneal approach was performed and multiple nodules were noted extending into the retroperitoneum. It was thought unlikely that complete resection had been achieved. His blood pressure returned to normal post-operatively, although hypokalaemia persisted. Histological examination, from this second operation, showed features of an adrenocortical carcinoma (ACC; including increased mitoses and invasion of fat) that was assessed as malignant using the scoring systems of Weiss and Aubert. Biochemical hyperaldosteronism persisted post-operatively, and detailed urine steroid profiling showed no evidence of adrenal steroid precursors or other mineralocorticoid production. He received flank radiotherapy to the left adrenal bed and continues to receive adjunctive mitotane therapy for a diagnosis of a pure aldosterone-secreting ACC. LEARNING POINTS: Pure aldosterone-secreting ACCs are exceptionally uncommon, but should be considered in the differential diagnosis of patients presenting with primary aldosteronism.Aldosterone-producing ACCs may not necessarily show typical radiological features consistent with malignancy.Patients who undergo surgical treatment for primary aldosteronism should have follow-up measurements of blood pressure to monitor for disease recurrence, even if post-operative normotension is thought to indicate a surgical 'cure'.Owing to the rarity of such conditions, a greater understanding of their natural history is likely to come from wider cooperation with, and contribution to, large multi-centre outcomes databases. PMID- 26273476 TI - Perceived Impact of Care Managers' Work on Patient and Clinician Outcomes. AB - OBJECTIVES: The aim of this study is to assess the contributions of care management as perceived by care managers themselves. STUDY DESIGN: Focus groups and interviews with care managers who coordinate care for chronic obstructive pulmonary disease and congestive heart failure patients, as well as patients undergoing major surgery. METHODS: We collected data in focus groups and interviews with 12 care managers working in the Keystone Beacon Community project, including 5 care managers working in hospitals, 2 employed in outpatient clinics and 4 telephoning discharged patients from a Transitions of Care (TOC) call center. RESULTS: Inpatient care managers believe that (1) ensuring primary care provider follow-up, (2) coordinating appropriate services, (3) providing patient education, and (4) ensuring accurate medication reconciliation have the greatest impact on patient clinical outcomes. In contrast, outpatient and TOC care managers believe that (1) teaching patients the signs and symptoms of acute exacerbations and (2) building effective relationships with patients improve patient outcomes most. Some care management activities were perceived to have greater impact on patients with certain conditions (e.g., outpatient and TOC care managers saw effective relationships as having more impact on patients with COPD). All care managers believed that relationships with patients have the greatest impact on patient satisfaction, while the support they provide clinicians has the greatest impact on clinician satisfaction. CONCLUSIONS: These findings may improve best practice for care managers by focusing interventions on the most effective activities for patients with specific medical conditions. PMID- 26273477 TI - Therapeutic Effect of Saponin Rich Fraction of Achyranthes aspera Linn. on Adjuvant-Induced Arthritis in Sprague-Dawley Rats. AB - Objective. Achyranthes aspera Linn. (AA) is used in folklore for the treatment of various inflammatory ailments and arthritis like conditions. Anti-inflammatory activity of saponin rich (SR) fraction of AA has been previously reported. The objective of this study was to assess the antiarthritic effect of SR fraction of Achyranthes aspera in adjuvant-induced arthritic rats. Methods. Arthritis was assessed by arthritis score, paw volume, changes in tibiotarsal joint thickness, hyperalgesic parameters, and spleen and thymus index. Haematological, serum, biochemical, and inflammatory cytokine and in vivo antioxidant parameters were measured on the last day of the study. Results. SR fraction significantly suppressed paw swelling and arthritic score and improved the pain threshold in motility and stair climbing tests. There was a reversal in the levels of altered parameters, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and antioxidant parameters like superoxide dismutase, catalase, glutathione, malondialdehyde, and nitric oxide. SR fraction significantly decreased plasma levels of tumor necrosis factor-alpha and interleukin-6. Moreover, histopathology revealed a significant reduction in synovial hyperplasia, inflammatory cell infiltration, and bone destruction in the joints. Conclusion. These observations explain the therapeutic benefit of SR fraction of AA in suppressing the progression of adjuvant-induced arthritis in rats. PMID- 26273479 TI - Less Than One-Third of Caretakers Sought Formal Health Care Facilities for Common Childhood Illnesses in Ethiopia: Evidence from the 2011 Ethiopian Demographic Health Survey. AB - Background. Most of the childhood illnesses can be proven with effective interventions. However, countless children die needlessly in developing countries due to the failure of their guardians to seek care timely. The aim of this study was to assess health care seeking behavior of caretakers of children under the age of five years for treatment of common childhood illnesses. Methods. Further analysis of the Ethiopian 2011 demographic and health survey was done. All children under the age of five reported to have been ill from the three common childhood illnesses and their caretakers were included in the analysis. A complex sample logistic regression model was employed to determine factors associated with the health care seeking behavior of caretakers. Result. A total of 2,842 caregivers who reported that their index child had at least one of the three common childhood illnesses in the two weeks preceding the survey were captured, of which 849 (29.87%; 95% CI: 28, 32%) sought formal health care facilities. Conclusion and Recommendation. In Ethiopia health care seeking behavior of caretakers for common childhood illnesses is low. Increasing mass media exposure can possibly improve the health seeking behavior of caretakers. PMID- 26273478 TI - Fructosamine and Hemoglobin A1c Correlations in HIV-Infected Adults in Routine Clinical Care: Impact of Anemia and Albumin Levels. AB - Fructosamine is an alternative method to hemoglobin A1c (HbA1c) for determining average glycemia. However, its use has not been extensively evaluated in persons living with HIV (PLWH). We examined the relationship between HbA1c and fructosamine values, specifically focusing on anemia (which can affect HbA1c) and albumin as a marker of liver disease. We included 345 PLWH from two sites. We examined Spearman rank correlations between fructosamine and HbA1c and performed linear test for trends to compare fructosamine and HbA1c correlations by hemoglobin and albumin quartiles. We examined discrepant individuals with values elevated only on one test. We found a correlation of 0.70 between fructosamine and HbA1c levels. Trend tests for correlations between fructosamine and HbA1c were significant for both albumin (p = 0.05) and hemoglobin (p = 0.01) with the lowest correlations in the lowest hemoglobin quartile. We identified participants with unremarkable HbA1c values but elevated fructosamine values. These discrepant individuals had lower mean hemoglobin levels than those elevated by both tests. We demonstrated a large correlation between HbA1c and fructosamine across a range of hemoglobin and albumin levels. There were discrepant cases particularly among those with lower hemoglobin levels. Future studies are needed to clarify the use of fructosamine for diabetes management in PWLH. PMID- 26273480 TI - Health Status and Health Determinants of Older Immigrant Women in Canada: A Scoping Review. AB - Increasing international migration in the context of aging populations makes a comprehensive understanding of older immigrant women's health status and determinants of their health particularly urgent. Using Arksey and O'Malley's framework, we conducted a scoping review to examine the available literature on the health of older immigrant women in Canada. We searched CINAHL, PsycINFO, Embase, Medline, and Cochrane databases for the period of 1990 to 2014 for Canadian-based, peer-reviewed studies on the topic. A total of 20 articles met the inclusion criteria. These articles were divided into six areas of focus: physical health; mental health; abuse; health promotion and chronic disease prevention; barriers to healthcare access and utilization; and health beliefs, behaviours, and practices. Our results show that the health of older immigrant women is affected by the interplay of various social determinants of health including the physical and social environment; economic conditions; cultural beliefs; gendered norms; and the healthcare delivery system. Our results also revealed that older immigrant women tend to have more health problems, underutilize preventive services, such as cancer screening, and experience more difficulties in accessing healthcare services. PMID- 26273482 TI - Successful Pregnancy in a Couple with Severe Male Factor Infertility after Selection of Sperm with Cytoplasmic Droplets. AB - We present live births resulting from two separate IVF cycles in a couple in which ICSI was performed with sperm specifically selected for presence of small cytoplasmic droplets. These cycles followed previous cycles using standard sperm selection methods in which very poor embryo development and no pregnancies ensued. The male partner was diagnosed with severe male factor infertility including elevated DNA fragmentation. PMID- 26273483 TI - Pregnancy in a Previously Conjoined Thoracopagus Twin with a Crisscross Heart. AB - Background. Crisscross heart (CCH) is a complex, rare, congenital, rotational, cardiac abnormality that accounts for <0.1% of congenital heart defects (CHD). CCH is characterized by the crossing of the inflow streams of the two ventricles due to an abnormal twisting of the heart. A case of maternal CCH has not been previously reported. Case. We report a case of a primigravida with a CCH, who was separated at birth from her thoracopagus conjoined twin. Pregnancy was managed by congenital cardiology, maternal-fetal medicine, anesthesiology, and obstetrics. She underwent a 39-week vaginal delivery without maternal or neonatal complication. Conclusion. A successful term pregnancy outcome was achieved in a patient with CCH using a multidisciplinary approach to address her cardiac condition. PMID- 26273484 TI - Surgical Correction of Posttraumatic Scapulothoracic Bursitis, Rhomboid Major Muscle Injury, Ipsilateral Glenohumeral Instability, and Headaches Resulting from Circus Acrobatic Maneuvers. AB - We report the case of a 28-year-old transgender (male-to-female) patient that had a partial tear of the rhomboid major tendon, scapulothoracic bursitis, and glenohumeral instability on the same side. These conditions resulted from traumatic events during circus acrobatic maneuvers. Additional aspects of this case that make it unique include (1) the main traumatic event occurred during a flagpole exercise, where the patient's trunk was suspended horizontally while a vertical pole was grasped with both hands, (2) headaches were associated with the periscapular injury and they improved after scapulothoracic bursectomy and rhomboid tendon repair, (3) surgical correction was done during the same operation with an open anterior capsular-labral reconstruction, open scapulothoracic bursectomy without bone resection, and rhomboid tendon repair, (4) a postoperative complication of tearing of the serratus anterior and rhomboid muscle attachments with recurrent scapulothoracic pain occurred from patient noncompliance, and (5) the postoperative complication was surgically corrected and ultimately resulted in an excellent outcome at the one-year final follow-up. PMID- 26273485 TI - Pulmonary Sequestration: Early Diagnosis and Management. AB - Intralobar sequestration is characterized by aberrant formation of nonfunctional lung tissue that has no communication with the bronchial tree and receives systemic arterial blood supply. Failure of earlier diagnosis can lead to recurrent pneumonia, failure to thrive, multiple hospital admissions, and more morbidity. The aim of this case report is to increase the awareness about the lung sequestration, to diagnose and treat it early, so that it is resected before repeated infection, and prevent the morbidity and mortality. PMID- 26273481 TI - Microglia-Induced Maladaptive Plasticity Can Be Modulated by Neuropeptides In Vivo. AB - Microglia-induced maladaptive plasticity is being recognized as a major cause of deleterious self-sustaining pathological processes that occur in neurodegenerative and neuroinflammatory diseases. Microglia, the primary homeostatic guardian of the central nervous system, exert critical functions both during development, in neural circuit reshaping, and during adult life, in the brain physiological and pathological surveillance. This delicate critical role can be disrupted by neural, but also peripheral, noxious stimuli that can prime microglia to become overreactive to a second noxious stimulus or worsen underlying pathological processes. Among regulators of microglia, neuropeptides can play a major role. Their receptors are widely expressed in microglial cells and neuropeptide challenge can potently influence microglial activity in vitro. More relevantly, this regulator activity has been assessed also in vivo, in experimental models of brain diseases. Neuropeptide action in the central nervous system has been associated with beneficial effects in neurodegenerative and neuroinflammatory pathological experimental models. This review describes some of the mechanisms of the microglia maladaptive plasticity in vivo and how neuropeptide activity can represent a useful therapeutical target in a variety of human brain pathologies. PMID- 26273486 TI - Immunoadjuvant Therapy and Noninvasive Ventilation for Acute Respiratory Failure in Lung Tuberculosis: A Case Study. AB - Acute respiratory failure caused by pulmonary tuberculosis is a rare event but with a high mortality even while receiving mechanical ventilatory support. We report the case of a young man with severe pulmonary tuberculosis refractory to conventional therapy who successfully overcame the critical period of his condition using noninvasive ventilation and immunoadjuvant therapy that included three doses of etanercept 25 mg subcutaneously. We conclude that the use of etanercept along with antituberculosis treatment appears to be safe and effective in patients with pulmonary tuberculosis presenting with acute respiratory failure. PMID- 26273487 TI - Talcoma: A Diagnostic Challenge in Differential Diagnosis of Pleural Masses. AB - Talcoma is a pleural mass which may develop as a rare complication following talc pleurodesis. Talc pleurodesis is performed to obliterate the pleural space to prevent recurrent pleural effusions or persistent pneumothoraces. The present report describes a case of a patient who developed enlarging pleural mass (talcoma) following talc pleurodesis. PMID- 26273488 TI - A Rare Complication of Biliary Stent Migration: Small Bowel Perforation in a Patient with Incisional Hernia. AB - Endoscopic biliary stents have been recently applied with increasing frequency as a palliative and curable method in several benign and malignant diseases. As a reminder, although most of the migrated stents pass through the intestinal tract without symptoms, a small portion can lead to complications. Herein, we present a case of intestinal perforation caused by a biliary stent in the hernia of a patient with a rarely encountered incarcerated incisional hernia. PMID- 26273490 TI - Inaugural Editorial. PMID- 26273489 TI - An Improved Micropropagation Protocol by Ex Vitro Rooting of Passiflora edulis Sims. f. flavicarpa Deg. through Nodal Segment Culture. AB - A procedure for rapid clonal propagation of Passiflora edulis Sims. f. flavicarpa Deg. (Passifloraceae) has been developed in this study. Nodal explants were sterilized with 0.1% HgCl2 and inoculated on Murashige and Skoog (MS) basal medium. The addition of 2.0 mgL(-1) 6-benzylaminopurine (BAP) to MS medium caused an extensive proliferation of multiple shoots (8.21 +/- 1.13) primordial from the nodal meristems. Subculturing of these multiple shoots on the MS medium augmented with 1.0 mgL(-1) of each BAP and Kinetin (Kin) was successful for the multiplication of the shoots in vitro with maximum numbers of shoots (25.73 +/- 0.06) within four weeks of incubation. Shoots were rooted best (7.13 +/- 0.56 roots/shoots) on half strength MS medium supplemented with 2.0 mgL(-1) indole-3 butyric acid (IBA). All in vitro regenerated shoots were rooted by ex vitro method, and this has achieved 6-7 roots per shoot by pulsing of cut ends of the shoots using 200 as well as 300 mgL(-1) IBA. The plantlets were hardened in the greenhouse for 4-5 weeks. The hardened plantlets were shifted to manure containing nursery polybags after five weeks and then transferred to a sand bed for another four weeks for acclimatization before field planting with 88% survival rate. PMID- 26273491 TI - Osteoclasts: New Insights. AB - Osteoclasts, the bone-resorbing cells, play a pivotal role in skeletal development and adult bone remodeling. They also participate in the pathogenesis of various bone disorders. Osteoclasts differentiate from cells of the monocyte/macrophage lineage upon stimulation of two essential factors, the monocyte/macrophage colony stimulating factor (M-CSF) and receptor activation of NF-kappaB ligand (RANKL). M-CSF binds to its receptor c-Fms to activate distinct signaling pathways to stimulate the proliferation and survival of osteoclast precursors and the mature cell. RANKL, however, is the primary osteoclast differentiation factor, and promotes osteoclast differentiation mainly through controlling gene expression by activating its receptor, RANK. Osteoclast function depends on polarization of the cell, induced by integrin alphavbeta3, to form the resorptive machinery characterized by the attachment to the bone matrix and the formation of the bone-apposed ruffled border. Recent studies have provided new insights into the mechanism of osteoclast differentiation and bone resorption. In particular, c-Fms and RANK signaling have been shown to regulate bone resorption by cross-talking with those activated by integrin alphavbeta3. This review discusses new advances in the understanding of the mechanisms of osteoclast differentiation and function. PMID- 26273494 TI - Osteoblast-restricted Disruption of the Growth Hormone Receptor in Mice Results in Sexually Dimorphic Skeletal Phenotypes. AB - Growth hormone (GH) exerts profound anabolic actions during postnatal skeletal development, in part, through stimulating the production of insulin-like growth factor-1 (IGF-1) in liver and skeletal tissues. To examine the requirement for the GH receptor (GHR) in osteoblast function in bone, we used Cre-LoxP methods to disrupt the GHR from osteoblasts, both in vitro and in vivo. Disruption of GHR from primary calvarial osteoblasts in vitro abolished GH-induced signaling, as assessed by JAK2/STAT5 phosphorylation, and abrogated GH-induced proliferative and anti-apoptotic actions. Osteoblasts lacking GHR exhibited reduced IGF-1 induced Erk and Akt phosphorylation and attenuated IGF-1-induced proliferation and anti-apoptotic action. In addition, differentiation was modestly impaired in osteoblasts lacking GHR, as demonstrated by reduced alkaline phosphatase staining and calcium deposition. In order to determine the requirement for the GHR in bone in vivo, we generated mice lacking the GHR specifically in osteoblasts (DeltaGHR), which were born at the expected Mendelian frequency, had a normal life span and were of normal size. Three week-old, female DeltaGHR mice had significantly reduced osteoblast numbers, consistent with the in vitro data. By six weeks of age however, female DeltaGHR mice demonstrated a marked increase in osteoblasts, although mineralization was impaired; a phenotype similar to that observed previously in mice lacking IGF-1R specifically in osteoblasts. The most striking phenotype occurred in male mice however, where disruption of the GHR from osteoblasts resulted in a "feminization" of bone geometry in 16 week-old mice, as observed by MUCT. These results demonstrate that the GHR is required for normal postnatal bone development in both sexes. GH appears to serve a primary function in modulating local IGF-1 action. However, the changes in bone geometry observed in male DeltaGHR mice suggest that, in addition to facilitating IGF-1 action, GH may function to a greater extent than previously appreciated in establishing the sexual dimorphism of the skeleton. PMID- 26273493 TI - Bone Remodeling and Energy Metabolism: New Perspectives. AB - Bone mineral, adipose tissue and energy metabolism are interconnected by a complex and multilevel series of networks. Calcium and phosphorus are utilized for insulin secretion and synthesis of high energy compounds. Adipose tissue store lipids and cholecalciferol, which, in turn, can influence calcium balance and energy expenditure. Hormones long-thought to solely modulate energy and mineral homeostasis may influence adipocytic function. Osteoblasts are a target of insulin action in bone. Moreover, endocrine mediators, such as osteocalcin, are synthesized in the skeleton but regulate carbohydrate disposal and insulin secretion. Finally, osteoblasts and adipocytes originate from the same mesenchymal progenitor. The mutual crosstalk between osteoblasts and adipocytes within the bone marrow microenvironment plays a crucial role in bone remodeling. In the present review we provide an overview of the reciprocal control between bone and energy metabolism and its clinical implications. PMID- 26273495 TI - Dynamic Fluid Flow Mechanical Stimulation Modulates Bone Marrow Mesenchymal Stem Cells. AB - Osteoblasts are derived from mesenchymal stem cells (MSCs), which initiate and regulate bone formation. New strategies for osteoporosis treatments have aimed to control the fate of MSCs. While functional disuse decreases MSC growth and osteogenic potentials, mechanical signals enhance MSC quantity and bias their differentiation toward osteoblastogenesis. Through a non-invasive dynamic hydraulic stimulation (DHS), we have found that DHS can mitigate trabecular bone loss in a functional disuse model via rat hindlimb suspension (HLS). To further elucidate the downstream cellular effect of DHS and its potential mechanism underlying the bone quality enhancement, a longitudinal in vivo study was designed to evaluate the MSC populations in response to DHS over 3, 7, 14, and 21 days. Five-month old female Sprague Dawley rats were divided into three groups for each time point: age-matched control, HLS, and HLS+DHS. DHS was delivered to the right mid-tibiae with a daily "10 min on-5 min off-10 min on" loading regime for five days/week. At each sacrifice time point, bone marrow MSCs of the stimulated and control tibiae were isolated through specific cell surface markers and quantified by flow cytometry analysis. A strong time-dependent manner of bone marrow MSC induction was observed in response to DHS, which peaked on day 14. After 21 days, this effect of DHS was diminished. This study indicates that the MSC pool is positively influenced by the mechanical signals driven by DHS. Coinciding with our previous findings of mitigation of disuse bone loss, DHS induced changes in MSC number may bias the differentiation of the MSC population towards osteoblastogenesis, thereby promoting bone formation under disuse conditions. This study provides insights into the mechanism of time-sensitive MSC induction in response to mechanical loading, and for the optimal design of osteoporosis treatments. PMID- 26273496 TI - Endogenous Glucocorticoids and Bone. AB - While the adverse effects of glucocorticoids on bone are well described, positive effects of glucocorticoids on the differentiation of osteoblasts are also observed. These paradoxical effects of glucocorticoids are dose dependent. At both physiologicaland supraphysiological levels of glucocorticoids, osteoblasts and osteocytes are the major glucocorticoid target cells. However, the response of the osteoblasts to each of these is quite distinct. At physiology levels, glucocorticoids direct mesenchymal progenitor cells to differentiate towards osteoblasts and thus increase bone formation in a positive way. In contrast with ageing, the excess production of glucocorticoids, at both systemic and intracellular levels, appear to impact on osteoblast and osteocytes in a negative way in a similar fashion to that seen with therapeutic glucocorticoids. This review will focus on therole of glucocorticoids in normal bone physiology, with particular emphasis on the mechanism by which endogenous glucocorticoids impact on bone and its constituent cells. PMID- 26273492 TI - A Comprehensive Overview of Skeletal Phenotypes Associated with Alterations in Wnt/beta-catenin Signaling in Humans and Mice. AB - The Wnt signaling pathway plays key roles in differentiation and development and alterations in this signaling pathway are causally associated with numerous human diseases. While several laboratories were examining roles for Wnt signaling in skeletal development during the 1990s, interest in the pathway rose exponentially when three key papers were published in 2001-2002. One report found that loss of the Wnt co-receptor, Low-density lipoprotein related protein-5 (LRP5), was the underlying genetic cause of the syndrome Osteoporosis pseudoglioma (OPPG). OPPG is characterized by early-onset osteoporosis causing increased susceptibility to debilitating fractures. Shortly thereafter, two groups reported that individuals carrying a specific point mutation in LRP5 (G171V) develop high-bone mass. Subsequent to this, the causative mechanisms for these observations heightened the need to understand the mechanisms by which Wnt signaling controlled bone development and homeostasis and encouraged significant investment from biotechnology and pharmaceutical companies to develop methods to activate Wnt signaling to increase bone mass to treat osteoporosis and other bone disease. In this review, we will briefly summarize the cellular mechanisms underlying Wnt signaling and discuss the observations related to OPPG and the high-bone mass disorders that heightened the appreciation of the role of Wnt signaling in normal bone development and homeostasis. We will then present a comprehensive overview of the core components of the pathway with an emphasis on the phenotypes associated with mice carrying genetically engineered mutations in these genes and clinical observations that further link alterations in the pathway to changes in human bone. PMID- 26273497 TI - FGF23 and Phosphate Wasting Disorders. AB - A decade ago, only two hormones, parathyroid hormone and 1,25(OH)2D, were widely recognized to directly affect phosphate homeostasis. Since the discovery of fibroblast growth factor 23 (FGF23) in 2000 (1), our understanding of the mechanisms of phosphate homeostasis and of bone mineralization has grown exponentially. FGF23 is the link between intestine, bone, and kidney together in phosphate regulation. However, we still do not know the complex mechanism of phosphate homeostasis and bone mineralization. The physiological role of FGF23 is to regulate serum phosphate. Secreted mainly by osteocytes and osteoblasts in the skeleton (2,3), it modulates kidney handling of phosphate reabsorption and calcitriol production. Genetic and acquired abnormalities in FGF23 structure and metabolism cause conditions of either hyper-FGF23 or hypo-FGF23. Hyper-FGF23 is related to hypophosphatemia, while hypo-FGF23 is related to hyperphosphatemia. Both hyper-FGF23 and hypo-FGF23 are detrimental to humans. In this review, we will discuss the pathophysiology of FGF23 and hyper-FGF23 related renal phosphate wasting disorders (4). PMID- 26273498 TI - Osteogenesis of Adipose-Derived Stem Cells. AB - Current treatment options for skeletal repair, including immobilization, rigid fixation, alloplastic materials and bone grafts, have significant limitations. Bone tissue engineering offers a promising method for the repair of bone deficieny caused by fractures, bone loss and tumors. The use of adipose derived stem cells (ASCs) has received attention because of the self-renewal ability, high proliferative capacity and potential of osteogenic differentiation in vitro and in vivo studies of bone regeneration. Although cell therapies using ASCs are widely promising in various clinical fields, no large human clinical trials exist for bone tissue engineering. The aim of this review is to introduce how they are harvested, examine the characterization of ASCs, to review the mechanisms of osteogenic differentiation, to analyze the effect of mechanical and chemical stimuli on ASC osteodifferentiation, to summarize the current knowledge about usage of ASC in vivo studies and clinical trials, and finally to conclude with a general summary of the field and comments on its future direction. PMID- 26273500 TI - Primary Hyperparathyroidism: A Tale of Two Cities Revisited - New York and Shanghai. AB - In the 1970s, with the advent of biochemical multichannel screening in the United States and other western countries, the clinical presentation of primary hyperparathyroidism (PHPT) changed from a symptomatic to an asymptomatic disorder. However, in Asian countries, like China, PHPT did not show this evolution, but rather continued to be a symptomatic disease with target organ involvement. In this paper, we revisit the clinical features of PHPT in New York and Shanghai, representative United States and Chinese cites, over the past decade. The questions we address are whether the disease evolved in China to a more asymptomatic one and, whether in the United States further changes are evident. The results indicate that while PHPT continues to present primarily as an asymptomatic disease in the United States, a new phenotype characterized by normal serum calcium and high parathyroid hormone levels, normocalcemic PHPT, has emerged. Data from Shanghai demonstrates a trend for PHPT to present more commonly as an asymptomatic disorder in China. However, most patients with PHPT in China still manifest classical symptoms, i.e. nephrolithiasis and fractures. A comparison of the two cohorts shows that Chinese patients with PHPT are younger, with higher serum calcium and PTH levels, and lower 25-hydroxyvitamin D levels than patients in New York. Normocalcemic PHPT has not yet been recognized in Shanghai. In summary, although the phenotypes of PHPT in both cities are evolving towards less evident disease, sharp clinical and biochemical differences are still apparent in PHPT as expressed in China and the United States. PMID- 26273499 TI - Role and Mechanisms of Actions of Thyroid Hormone on the Skeletal Development. AB - The importance of the thyroid hormone axis in the regulation of skeletal growth and maintenance has been well established from clinical studies involving patients with mutations in proteins that regulate synthesis and/or actions of thyroid hormone. Data from genetic mouse models involving disruption and overexpression of components of the thyroid hormone axis also provide direct support for a key role for thyroid hormone in the regulation of bone metabolism. Thyroid hormone regulates proliferation and/or differentiated actions of multiple cell types in bone including chondrocytes, osteoblasts and osteoclasts. Thyroid hormone effects on the target cells are mediated via ligand-inducible nuclear receptors/transcription factors, thyroid hormone receptor (TR) alpha and beta, of which TRalpha seems to be critically important in regulating bone cell functions. In terms of mechanisms for thyroid hormone action, studies suggest that thyroid hormone regulates a number of key growth factor signaling pathways including insulin-like growth factor-I, parathyroid hormone related protein, fibroblast growth factor, Indian hedgehog and Wnt to influence skeletal growth. In this review we describe findings from various genetic mouse models and clinical mutations of thyroid hormone signaling related mutations in humans that pertain to the role and mechanism of action of thyroid hormone in the regulation of skeletal growth and maintenance. PMID- 26273501 TI - microRNA Expression in Rat Apical Periodontitis Bone Lesion. AB - Apical periodontitis, dominated by dense inflammatory infiltrates and increased osteoclast activities, can lead to alveolar bone destruction and tooth loss. It is believed that miRNA participates in regulating various biological processes, osteoclastogenesis included. This study aims to investigate the differential expression of miRNAs in rat apical periodontitis and explore their functional target genes. Microarray analysis was used to identify differentially expressed miRNAs in apical periodontitis. Bioinformatics technique was applied for predicting the target genes of differentially expressed miRNAs and their biological functions. The result provided us with an insight into the potential biological effects of the differentially expressed miRNAs and showed particular enrichment of target genes involved in the MAPK signaling pathways. These findings may highlight the intricate and specific roles of miRNA in inflammation and osteoclastogenesis, both of which are key aspects of apical periodontitis, thus contributing to the future investigation into the etiology, underlying mechanism and treatment of apical periodontitis. PMID- 26273502 TI - IGF-1 Signaling is Essential for Differentiation of Mesenchymal Stem Cells for Peak Bone Mass. AB - Survival of children with chronic medical illnesses is leading to an increase in secondary osteoporosis due to impaired peak bone mass (PBM). Insulin-like growth factor type 1 (IGF-1) levels correlate with the pattern of bone mass accrual and many chronic illnesses are associated with low IGF-1 levels. Reduced serum levels of IGF-1 minimally affect the integrity of the skeleton, whereas recent studies suggest that skeletal IGF-I regulates PBM. To determine the role of IGF-1 in postnatal bone mass accrual regardless of source, we established an inducible type 1 Igf receptor Cre/lox knockout mouse model, in which the type 1 Igf receptor was deleted inducibely in the mesenchymal stem cells (MSCs) from 3-7 weeks of age. The size of the mouse was not affected as knockout and wild type mice had similar body weights and nasoanal and femoral lengths. However, bone volume and trabecular bone thickness were decreased in the secondary spongiosa of female knockout mice relative to wild type controls, indicating that IGF-1 is critical for bone mass. IGF-1 signaling in MSCs in vitro has been implicated to be involved in both migration to the bone surface and differentiation into bone forming osteoblasts. To clarify the exact role of IGF-1 in bone, we found by immunohistochemical analysis that a similar number of Osterix-positive osteoprogenitors were on the bone perimeter, indicating migration of MSCs was not affected. Most importantly, 56% fewer osteocalcin-positive mature osteoblasts were present on the bone perimeter in the secondary spongiosa in knockout mice versus wild type littermates. These in vivo data demonstrate that the primary role of skeletal IGF-1 is for the terminal differentiation of osteoprogenitors, but refute the role of IGF-1 in MSC migration in vivo. Additionally, these findings confirm that impaired IGF-1 signaling in bone MSCs is sufficient to impair bone mass acquisition. PMID- 26273503 TI - The Craniofacial Morphology in Adult Patients with Unoperated Isolated Cleft Palate. AB - OBJECTIVE: To address the effect of intrinsic factors on craniofacial growth by analyzing the craniofacial morphology of unoperated isolated cleft palate in Chinese adult. MATERIALS AND METHODS: This study included 37 nonsyndromic isolated cleft palate and 39 age and gender matched non-clefts. Twenty-six cephalometric measurements were employed to evaluate the facial morphology. Independent samples T test and Mann-Whitney U were used for comparison. Significant difference was defined at 95% level. RESULTS: Data from this study showed patients with unoperated isolated cleft palate have a reduced maxillary sagittal length (ANS-PMP, A-PMP, P<0.05), a smaller ANB angle (ANB, P<0.05) and a retrusive ANS point (S-N-ANS, P<0.05; Ba-N-ANS, P<0.05). Measurements descripted position of maxilla (S-Ptm, P>0.05), depth of bony pharynx (Ba-PMP, P>0.05), anterior and posterior maxillary height (N-ANS, P>0.05; R-PMP, P>0.05) and mandible morphology (including linear measurements and angle measurements) did not show any significant difference between case and control groups. CONCLUSIONS: Patients with isolated cleft palate were characterized by maxillary retrusion. Mandible morphology and cranial basal morphology in isolated cleft palate showed no significant difference with nonclefts. Patients with isolated cleft palate are more vulnerable to cross bite than nonclefts. Intrinsic deficiencies did detrimental effect on maxilla sagittal length, but did no detrimental effect on maxilla position, mandible size and position. PMID- 26273504 TI - The Key Role of the Blood Supply to Bone. AB - The importance of the vascular supply for bone is well-known to orthopaedists but is still rather overlooked within the wider field of skeletal research. Blood supplies oxygen, nutrients and regulatory factors to tissues, as well as removing metabolic waste products such as carbon dioxide and acid. Bone receives up to about 10% of cardiac output, and this blood supply permits a much higher degree of cellularity, remodelling and repair than is possible in cartilage, which is avascular. The blood supply to bone is delivered to the endosteal cavity by nutrient arteries, then flows through marrow sinusoids before exiting via numerous small vessels that ramify through the cortex. The marrow cavity affords a range of vascular niches that are thought to regulate the growth and differentiation of hematopoietic and stromal cells, in part via gradients of oxygen tension. The quality of vascular supply to bone tends to decline with age and may be compromised in common pathological settings, including diabetes, anaemias, chronic airway diseases and immobility, as well as by tumours. Reductions in vascular supply are associated with bone loss. This may be due in part to the direct effects of hypoxia, which blocks osteoblast function and bone formation but causes reciprocal increases in osteoclastogenesis and bone resorption. Common regulatory factors such as parathyroid hormone or nitrates, both of which are potent vasodilators, might exert their osteogenic effects on bone via the vasculature. These observations suggest that the bone vasculature will be a fruitful area for future research. PMID- 26273507 TI - New Clues that May Link Osteoporosis to the Circulating Lipid Profile. AB - Bone Mineral Density (BMD) is a gold standard for the diagnosis of osteoporosis and is also important in the assessment of fracture risk. Other risk factors have been identified that together make up fracture risk assessment tools such as FRAX. Another potential factor, circulating lipids, has been suggested because of reports linking statins to fracture risk reduction. We analyzed the lipid profile in a cohort of women diagnosed with postmenopausal osteoporosis based on bone density determination: 610 women with osteoporosis (mean lumbar spine T-score 3.16+/-0.81, mean yrs. since menopause 15.79+/-8.9) were grouped according to age at evaluation (< 50 years, 51-60 years, 61-70 years, > 70 years), the presence/absence of a history of a fragility fracture, statin and/or antiresorptive drug use. There was no correlation between BMD and Body Mass Index (BMI: P>0.05, r (2)<0.02). However, when BMD was correlated with both BMI and the lipid profile (Triglycerides, Cholesterol, LDLc, HDLc), significant correlations were found in 5 cohorts: 51-60 years with fractures (n=61, r (2)=0.14, P<0.01), 61-70 years (n=201, r (2)=0.09, P<0.01) with fractures (n=88, r (2)=0.14, P<0.01) or without fractures (n=113, r (2)=0.24, P=0.02) and over 70 years (n=247, r (2)=0.11, P<0.01). PMID- 26273506 TI - Autocrine and Paracrine Actions of IGF-I Signaling in Skeletal Development. AB - Insulin-like growth factor-I (IGF-I) regulates cell growth, survival, and differentiation by acting on the IGF-I receptor, (IGF-IR)-a tyrosine kinase receptor, which elicits diverse intracellular signaling responses. All skeletal cells express IGF-I and IGF-IR. Recent studies using tissue/cell-specific gene knockout mouse models and cell culture techniques have clearly demonstrated that locally produced IGF-I is more critical than the systemic IGF-I in supporting embryonic and postnatal skeletal development and bone remodeling. Local IGF-I/IGF IR signaling promotes the growth, survival and differentiation of chondrocytes and osteoblasts, directly and indirectly, by altering other autocrine/paracrine signaling pathways in cartilage and bone, and by enhancing interactions among these skeletal cells through hormonal and physical means. Moreover, local IGF I/IGF-IR signaling is critical for the anabolic bone actions of growth hormone and parathyroid hormone. Herein, we review evidence supporting the actions of local IGF-I/IGF-IR in the above aspects of skeletal development and remodeling. PMID- 26273508 TI - Comparison of Effects of Mechanical Stretching on Osteogenic Potential of ASCs and BMSCs. AB - Mechanical forces play critical roles in the development and remodeling processes of bone. As an alternative cell source for bone engineering, adipose-derived stem cells (ASCs) should be fully investigated for their responses to mechanical stress. Similarly, the osteogenic potential, stimulated by mechanical stress, should be compared with bone marrow stromal cells (BMSCs), which have been clinically used for bone tissue engineering. In this study, ASCs and BMSCs were osteogenic-induced for 48 hours, and then subjected to uniaxial mechanical stretching for 2 or 6 hours. Cell orientation, osteogenic regulatory genes, osteogenic genes and ALP activities were measured and compared between ASCs and BMSCs. ASCs could align in a perpendicular way to the direction of stretching stress, while BMSCs did not present a specific alignment. Both 2 and 6 hours mechanical stretching could enhance the mRNA expression of Osx and Runx2 in BMSCs and ASCs, while OCN mRNA only increased in ASCs after 6 hours mechanical loading. Mechanical stretching enhanced the BMP-2 mRNA expression in ASCs, while only after 6 hours of mechanical loading significantly increased the BMP-2 gene expression in BMSCs. Significant differences only exist between ASCs and BMSCs loaded at 2 hours of mechanical stretching. It is concluded that ASCs are more rapid responders to mechanical stress, and have greater potential than BMSCs in osteogenesis when stimulated by mechanical stretching, indicating their usefulness for bone study in a rat model. PMID- 26273505 TI - Bone Regeneration Based on Tissue Engineering Conceptions - A 21st Century Perspective. AB - The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive (second generation) biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials (third generation) are designed to be not only osteoconductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineering and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental "origin" require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts. PMID- 26273510 TI - Osteoporosis Treatment: When to Discontinue and When to Re-start. AB - A number of effective therapies for the treatment of osteoporosis have become available in recent years. However, uncertainty exists regarding their long-term use and effectiveness. Bisphosphonate treatment, unlike hormone replacement, denosumab or teriparatide, is associated with benefits extended even after treatment discontinuation. The extended benefits are most apparent for alendronate (ALN) and zoledronate (ZOL). A drug holiday might be considered in patients at low-moderate risk and who have been fully compliant with treatment, and who have had a response to treatment. In patients at low-moderate risk of fractures the decision to consider a drug holiday should be balanced also with the safety profile of each treatment. PMID- 26273509 TI - Skeletal Blood Flow in Bone Repair and Maintenance. AB - Bone is a highly vascularized tissue, although this aspect of bone is often overlooked. In this article, the importance of blood flow in bone repair and regeneration will be reviewed. First, the skeletal vascular anatomy, with an emphasis on long bones, the distinct mechanisms for vascularizing bone tissue, and methods for remodeling existing vasculature are discussed. Next, techniques for quantifying bone blood flow are briefly summarized. Finally, the body of experimental work that demonstrates the role of bone blood flow in fracture healing, distraction osteogenesis, osteoporosis, disuse osteopenia, and bone grafting is examined. These results illustrate that adequate bone blood flow is an important clinical consideration, particularly during bone regeneration and in at-risk patient groups. PMID- 26273511 TI - Mice Deficient in NF-kappaB p50 and p52 or RANK Have Defective Growth Plate Formation and Post-natal Dwarfism. AB - NF-kappaBp50/p52 double knockout (dKO) and RANK KO mice have no osteoclasts and develop severe osteopetrosis associated with dwarfism. In contrast, Op/Op mice, which form few osteoclasts, and Src KO mice, which have osteoclasts with defective resorptive function, are osteopetrotic, but they are not dwarfed. Here, we compared the morphologic features of long bones from p50/p52 dKO, RANK KO, Op/Op and Src KO mice to attempt to explain the differences in their long bone lengths. We found that growth plates in p50/p52 dKO and RANK KO mice are significantly thicker than those in WT mice due to a 2-3-fold increase in the hypertrophic chondrocyte zone associated with normal a proliferative chondrocyte zone. This growth plate abnormality disappears when animals become older, but their dwarfism persists. Op/Op or Src KO mice have relatively normal growth plate morphology. In-situ hybridization study of long bones from p50/p52 dKO mice showed marked thickening of the growth plate region containing type 10 collagen expressing chondrocytes. Treatment of micro-mass chondrocyte cultures with RANKL did not affect expression levels of type 2 collagen and Sox9, markers for proliferative chondrocytes, but RANKL reduced the number of type 10 collagen expressing hypertrophic chondrocytes. Thus, RANK/NF-kappaB signaling plays a regulatory role in post-natal endochondral ossification that maintains hypertrophic conversion and prevents dwarfism in normal mice. PMID- 26273512 TI - Trabecular Plate Loss and Deteriorating Elastic Modulus of Femoral Trabecular Bone in Intertrochanteric Hip Fractures. AB - Osteoporotic hip fracture is associated with significant trabecular bone loss, which is typically characterized as low bone density by dual-energy X-ray absorptiometry (DXA) and altered microstructure by micro-computed tomography (MUCT). Emerging morphological analysis techniques, e.g. individual trabecula segmentation (ITS), can provide additional insights into changes in plate-like and rod-like trabeculae, two major microstructural types serving different roles in determining bone strength. Using ITS, we evaluated trabecular microstructure of intertrochanteric bone cores obtained from 23 patients undergoing hip replacement surgery for intertrochanteric fracture and 22 cadaveric controls. Micro-finite element (MUFE) analyses were performed to further understand how the abnormalities seen by ITS might translate into effects on bone strength. ITS analyses revealed that, near fracture site, plate-like trabeculae were seriously depleted in fracture patients, but trabecular rod volume was maintained. Besides, decreased plate area and rod length were observed in fracture patients. Fracture patients also showed decreased elastic moduli and shear moduli of trabecular bone. These results provided evidence that in intertrochanteric hip fracture, preferential loss of plate-like trabeculae led to more rod-like microstructure and deteriorated mechanical competence adjacent to the fracture site, which increased our understanding of the biomechanical pathogenesis of hip fracture in osteoporosis. PMID- 26273513 TI - Elevated Intracellular Ca(2+) Signals by Oxidative Stress Activate Connexin 43 Hemichannels in Osteocytes. AB - Elevated oxidative stress (OS) during aging leads to bone loss. OS increases intracellular Ca(2+) ([Ca(2+)]i), resulting in cellular damage and death. We show earlier that Cx43 hemichannels open in response to OS, which serves as a protective mechanism for osteocytes. However, the underlying mechanism is unknown. Here, we found that treatment with H2O2 increased [Ca(2+)]i in osteocytes with [Ca(2+)]i being primarily derived from an extracellular Ca(2+) source. Hemichannel opening induced by OS was inhibited by the depletion of [Ca(2+)]i with BAPTA-AM, a Ca(2+) chelator, suggesting that [Ca(2+)]i influenced the activity of Cx43 hemichannels. Conversely, blockade of hemichannels had no effect on [Ca(2+)]i. A biotinylation assay showed that cell surface-expressed Cx43 was increased by OS, which could be inhibited by BAPTA-AM, suggesting that [Ca(2+)]i is necessary for Cx43 migration to the cell surface in response to OS. Together, these data suggest that increased hemichannel activity induced by OS was likely to be caused by elevated [Ca(2+)]i through increased Cx43 on the cell surface. PMID- 26273514 TI - Suppressive Effects of Plumbagin on Invasion and Migration of Breast Cancer Cells via the Inhibition of STAT3 Signaling and Down-regulation of Inflammatory Cytokine Expressions. AB - OBJECTIVE: The aim of this study was to investigate the effects of plumbagin (PL), a naphthoquinone derived from the medicinal plant plumbago zeylanica, on the invasion and migration of human breast cancer cells. METHODS: Human breast cancer MDA-MB-231SArfp cells were treated with different concentrations of plumbagin for 24 h. The effects of plumbagin on the migration and invasion were observed by a transwell method. The expressions of IL-1alpha, IL-1beta, IL-6, IL 8, TGF-beta, TNFalpha, MMP-2 and MMP-9 mRNA in MDA-MB-231SArfp cells were detected using Real-Time PCR. MDA-MB-231SArfp cells were treated with plumbagin at different concentrations for 45 minutes. The activation of STAT3 was detected by western blot. Following this analysis, STAT3 in MDA-MB-231SArfp cells was knocked out using specific siRNA. mRNA levels of IL-1alpha, TGF-beta, MMP-2 and MMP-9 were then detected. Consequently, MDA-MB-231SArfp cells were injected intracardially into BALB/c nude mice to construct a breast cancer bone metastatic model. The mice were injected intraperitoneally with plumbagin. Non-invasive in vivo monitoring, X-ray imaging and histological staining were performed to investigate the effects of plumbagin on the invasion and migration of breast cancer cells in vivo. RESULTS: The in vitro results showed that plumbagin could suppress the migration and invasion of breast cancer cells and down-regulate mRNA expressions of IL-1alpha, TGF-beta, MMP-2 and MMP-9. Western blotting demonstrated that plumbagin inhibited the activation of STAT3 signaling in MDA-MB 231SArfp cells. The inactivation of STAT3 was found to have an inhibitory effect on the expressions of IL-1alpha, TGF-beta, MMP-2 and MMP-9. In vivo studies showed that plumbagin inhibited the metastasis of breast cancer cells and decreased osteolytic bone metastases, as well as the secretion of MMP-2 and MMP-9 by tumor cells at metastatic lesions. CONCLUSIONS: Plumbagin can suppress the invasion and migration of breast cancer cells via the inhibition of STAT3 signaling and by downregulation of IL-1alpha, TGF-beta, MMP-2 and MMP-9. PMID- 26273515 TI - Osteoporosis in men: a review. AB - Osteoporosis and consequent fracture are not limited to postmenopausal women. There is increasing attention being paid to osteoporosis in older men. Men suffer osteoporotic fractures about 10 years later in life than women, but life expectancy is increasing faster in men than women. Thus, men are living long enough to fracture, and when they do the consequences are greater than in women, with men having about twice the 1-year fatality rate after hip fracture, compared to women. Men at high risk for fracture include those men who have already had a fragility fracture, men on oral glucocorticoids or those men being treated for prostate cancer with androgen deprivation therapy. Beyond these high risk men, there are many other risk factors and secondary causes of osteoporosis in men. Evaluation includes careful history and physical examination to reveal potential secondary causes, including many medications, a short list of laboratory tests, and bone mineral density testing by dual energy X-ray absorptiometry (DXA) of spine and hip. Recently, international organizations have advocated a single normative database for interpreting DXA testing in men and women. The consequences of this change need to be determined. There are several choices of therapy for osteoporosis in men, with most fracture reduction estimation based on studies in women. PMID- 26273517 TI - Wnt7b can replace Ihh to induce hypertrophic cartilage vascularization but not osteoblast differentiation during endochondral bone development. AB - Indian hedgehog (Ihh) is an essential signal that regulates endochondral bone development. We have previously shown that Wnt7b promotes osteoblast differentiation during mouse embryogenesis, and that its expression in the perichondrium is dependent on Ihh signaling. To test the hypothesis that Wnt7b may mediate some aspects of Ihh function during endochondral bone development, we activated Wnt7b expression from the R26-Wnt7b allele with Col2-Cre in the Ihh(-/ ) mouse. Artificial expression of Wnt7b rescued vascularization of the hypertrophic cartilage in the Ihh(-/-) mouse, but failed to restore orthotopic osteoblast differentiation in the perichondrium. Similarly, Wnt7b did not recover Ihh-dependent perichondral bone formation in the Ihh(-/-); Gli3(-/-) embryo. Interestingly, Wnt7b induced bone formation at the diaphyseal region of long bones in the absence of Ihh, possibly due to increased vascularization in the area. Thus, Ihh-dependent expression of Wnt7b in the perichondrium may contribute to vascularization of the hypertrophic cartilage during endochondral bone development. PMID- 26273518 TI - Hypoxia-inducible factor-1alpha restricts the anabolic actions of parathyroid hormone. AB - The hypoxia inducible factors (Hifs) are evolutionarily conserved transcriptional factors that control homeostatic responses to low oxygen. In developing bone, Hif 1 generated signals induce angiogenesis necessary for osteoblast specification, but in mature bone, loss of Hif-1 in osteoblasts resulted in a more rapid accumulation of bone. These findings suggested that Hif-1 exerts distinct developmental functions and acts as a negative regulator of bone formation. To investigate the function of Hif-1alpha in osteoanabolic signaling, we assessed the effect of Hif-1alpha loss-of-function on bone formation in response to intermittent parathyroid hormone (PTH). Mice lacking Hif-1alpha in osteoblasts and osteocytes form more bone in response to PTH, likely through a larger increase in osteoblast activity and increased sensitivity to the hormone. Consistent with this effect, exposure of primary mouse osteoblasts to PTH resulted in the rapid induction of Hif-1alpha protein levels via a post transcriptional mechanism. The enhanced anabolic response appears to result from the removal of Hif-1alpha-mediated suppression of beta-catenin transcriptional activity. Together, these data indicate that Hif-1alpha functions in the mature skeleton to restrict osteoanabolic signaling. The availability of pharmacological agents that reduce Hif-1alpha function suggests the value in further exploration of this pathway to optimize the therapeutic benefits of PTH. PMID- 26273519 TI - LRP6 in mesenchymal stem cells is required for bone formation during bone growth and bone remodeling. AB - Lipoprotein receptor-related protein 6 (LRP6) plays a critical role in skeletal development and homeostasis in adults. However, the role of LRP6 in mesenchymal stem cells (MSCs), skeletal stem cells that give rise to osteoblastic lineage, is unknown. In this study, we generated mice lacking LRP6 expression specifically in nestin(+) MSCs by crossing nestin-Cre mice with LRP6(flox) mice and investigated the functional changes of bone marrow MSCs and skeletal alterations. Mice with LRP6 deletion in nestin(+) cells demonstrated reductions in body weight and body length at 1 and 3 months of age. Bone architecture measured by microCT (uCT) showed a significant reduction in bone mass in both trabecular and cortical bone of homozygous and heterozygous LRP6 mutant mice. A dramatic reduction in the numbers of osteoblasts but much less significant reduction in the numbers of osteoclasts was observed in the mutant mice. Osterix(+) osteoprogenitors and osteocalcin(+) osteoblasts significantly reduced at the secondary spongiosa area, but only moderately decreased at the primary spongiosa area in mutant mice. Bone marrow MSCs from the mutant mice showed decreased colony forming, cell viability and cell proliferation. Thus, LRP6 in bone marrow MSCs is essential for their survival and proliferation, and therefore, is a key positive regulator for bone formation during skeletal growth and remodeling. PMID- 26273520 TI - In vivo evidence of IGF-I-estrogen crosstalk in mediating the cortical bone response to mechanical strain. AB - Although insulin-like growth factor-I (IGF-I) and estrogen signaling pathways have been shown to be involved in mediating the bone anabolic response to mechanical loading, it is not known whether these two signaling pathways crosstalk with each other in producing a skeletal response to mechanical loading. To test this, at 5 weeks of age, partial ovariectomy (pOVX) or a sham operation was performed on heterozygous IGF-I conditional knockout (H IGF-I KO) and control mice generated using a Cre-loxP approach. At 10 weeks of age, a 10 N axial load was applied on the right tibia of these mice for a period of 2 weeks and the left tibia was used as an internal non-non-loaded control. At the cortical site, partial estrogen loss reduced total volumetric bone mineral density (BMD) by 5% in control pOVX mice (P=0.05, one-way ANOVA), but not in the H IGF-I KO pOVX mice. At the trabecular site, bone volume/total volume (BV/TV) was reduced by 5% 6% in both control pOVX (P<0.05) and H IGF-I KO pOVX (P=0.05) mice. Two weeks of mechanical loading caused a 7%-8% and an 11%-13% (P<0.05 vs. non-loaded bones) increase in cortical BMD and cortical thickness (Ct.Th), respectively, in the control sham, control pOVX and H IGF-I KO sham groups. By contrast, the magnitude of cortical BMD (4%, P=0.13) and Ct.Th (6%, P<0.05) responses were reduced by 50% in the H IGF-I KO pOVX mice compared to the other three groups. The interaction between genotype and estrogen deficiency on the mechanical loading-induced cortical bone response was significant (P<0.05) by two-way ANOVA. Two weeks of axial loading caused similar increases in trabecular BV/TV (13%-17%) and thickness (17%-23%) in all four groups of mice. In conclusion, partial loss of both estrogen and IGF-I significantly reduced cortical but not the trabecular bone response to mechanical loading, providing in vivo evidence of the above crosstalk in mediating the bone response to loading. PMID- 26273516 TI - Role of FGF/FGFR signaling in skeletal development and homeostasis: learning from mouse models. AB - Fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) signaling plays essential roles in bone development and diseases. Missense mutations in FGFs and FGFRs in humans can cause various congenital bone diseases, including chondrodysplasia syndromes, craniosynostosis syndromes and syndromes with dysregulated phosphate metabolism. FGF/FGFR signaling is also an important pathway involved in the maintenance of adult bone homeostasis. Multiple kinds of mouse models, mimicking human skeleton diseases caused by missense mutations in FGFs and FGFRs, have been established by knock-in/out and transgenic technologies. These genetically modified mice provide good models for studying the role of FGF/FGFR signaling in skeleton development and homeostasis. In this review, we summarize the mouse models of FGF signaling-related skeleton diseases and recent progresses regarding the molecular mechanisms, underlying the role of FGFs/FGFRs in the regulation of bone development and homeostasis. This review also provides a perspective view on future works to explore the roles of FGF signaling in skeletal development and homeostasis. PMID- 26273522 TI - Validating cone-beam computed tomography for peri-implant bone morphometric analysis. AB - Cone-beam computed tomography (CBCT) has been recently used to analyse trabecular bone structure around dental implants. To validate the use of CBCT for three dimensional (3D) peri-implant trabecular bone morphometry by comparing it to two dimensional (2D) histology, 36 alveolar bone samples (with implants n=27 vs. without implants n=9) from six mongrel dogs, were scanned ex vivo using a high resolution (80 um) CBCT. After scanning, all samples were decalcified and then sectioned into thin histological sections (~6 MUm) to obtain high contrast 2D images. By using CTAn imaging software, bone morphometric parameters including trabecular number (Tb.N), thickness (Tb.Th), separation (Tb.Sp) and bone volume fraction (BV/TV) were examined on both CBCT and corresponding histological images. Higher Tb.Th and Tb.Sp, lower BV/TV and Tb.N were found on CBCT images (P<0.001). Both measurements on the peri-implant trabecular bone structure showed moderate to high correlation (r=0.65-0.85). The Bland-Altman plots showed strongest agreement for Tb.Th followed by Tb.Sp, Tb.N and BV/TV, regardless of the presence of implants. The current findings support the assumption that peri implant trabecular bone structures based on high-resolution CBCT measurements are representative for the underlying histological bone characteristics, indicating a potential clinical diagnostic use of CBCT-based peri-implant bone morphometric characterisation. PMID- 26273521 TI - The Chinese skeleton: insights into microstructure that help to explain the epidemiology of fracture. AB - Osteoporotic fractures are a major public health problem worldwide, but incidence varies greatly across racial groups and geographic regions. Recent work suggests that the incidence of osteoporotic fracture is rising among Asian populations. Studies comparing areal bone mineral density and fracture across races generally indicate lower bone mineral density in Asian individuals including the Chinese, but this does not reflect their relatively low risk of non-vertebral fractures. In contrast, the Chinese have relatively high vertebral fracture rates similar to that of Caucasians. The paradoxically low risk for some types of fractures among the Chinese despite their low areal bone mineral density has been elucidated in part by recent advances in skeletal imaging. New techniques for assessing bone quality non-invasively demonstrate that the Chinese compensate for smaller bone size by differences in hip geometry and microstructural skeletal organization. Studies evaluating factors influencing racial differences in bone remodeling, as well as bone acquisition and loss, may further elucidate racial variation in bone microstructure. Advances in understanding the microstructure of the Chinese skeleton have not only helped to explain the epidemiology of fracture in the Chinese, but may also provide insight into the epidemiology of fracture in other races as well. PMID- 26273523 TI - Insulin exerts direct, IGF-1 independent actions in growth plate chondrocytes. AB - Insufficient insulin production or action in diabetic states is associated with growth retardation and impaired bone healing, while the underling mechanisms are unknown. In this study, we sought to define the role of insulin signaling in the growth plate. Insulin treatment of embryonic metatarsal bones from wild-type mice increased chondrocyte proliferation. Mice lacking insulin receptor (IR) selectively in chondrocytes (CartIR (-/-)) had no discernable differences in total femoral length compared to control littermates. However, CartIR (-/-) mice exhibited an increase in chondrocyte numbers in the growth plate than that of the controls. Chondrocytes lacking IR had elevated insulin-like growth factor (IGF) 1R mRNA and protein levels. Subsequently, IGF-1 induced phosphorylation of Akt and ERK was enhanced, while this action was eliminated when the cells were treated with IGF-1R inhibitor Picropodophyllin. Deletion of the IR impaired chondrogenic differentiation, and the effect could not be restored by treatment of insulin, but partially rescued by IGF-1 treatment. Intriguingly, the size of hypertrophic chondrocytes was smaller in CartIR (-/-) mice when compared with that of the control littermates, which was associated with upregulation of tuberous sclerosis complex 2 (TSC2). These results suggest that deletion of the IR in chondrocytes sensitizes IGF-1R signaling and action, IR and IGF-1R coordinate to regulate the proliferation, differentiation and hypertrophy of growth plate chondrocytes. PMID- 26273524 TI - Stability of unicortical locked fixation versus bicortical non-locked fixation for forearm fractures. AB - Locking plate fixation is being widely applied for fixation of forearm fractures and has many potential advantages, such as fixed angle fixation and improved construct stability, especially in osteoporotic bone. Biomechanical data comparing locking devices to commonly used Low Contact Dynamic Compression (LCDCP) plates for the fixation of forearm fractures has been lacking. The purpose of this study was to compare the fixation stability of a 3.5-mm unicortical locked plate with bicortical non-locked LCDCP plates. Six matched pairs of fresh frozen cadaveric forearms were randomly assigned to unicortical locked and bicortical unlocked groups. Non-destructive four-point bending and torsional test was performed on the ulna and radius separately, using a servohydraulic testing system to obtain construct stiffness of the intact specimens and specimens after osteotomy and plating. The specimens were then loaded to failure to test the fixation strength. The locked unicortical fixation showed significantly higher bending stiffness than the unlocked bicortical fixation, but with significantly lower stiffness and strength in torsion. Fixation strength was comparable between the two groups under bending, but significantly greater in the bicortical non-locked group under torsion. Findings from this study suggest that postoperative rehabilitation protocols may need modification to limit torsional loading in the early stage when using locked unicortical fixation. The study also points out the potential advantage of a hybrid fixation that combines locked unicortical and unlocked bicortical screws. PMID- 26273525 TI - Bone density, microarchitecture and stiffness in Caucasian and Caribbean Hispanic postmenopausal American women. AB - Hispanic Americans of Caribbean origin are a fast-growing subset of the US population, but there are no studies on bone density, microstructure and biomechanical integrity in this minority group. In this study, we aimed to compare Caucasian and Caribbean Hispanic postmenopausal American women with respect to these characteristics. Thirty-three Caribbean Hispanics were age matched to thirty-three Caucasian postmenopausal women. At the lumbar spine, the Hispanic women had significantly lower areal bone mineral density (aBMD). At the radius by high-resolution peripheral quantitative computed tomography (HR-pQCT), there were minimal differences between Hispanic and Caucasian women. At the tibia, Hispanic women had lower trabecular volumetric bone density and trabecular number, and higher trabecular separation. Individual trabecula segmentation (ITS) analyses indicated that at the tibia, Hispanic women not only had significantly lower bone volume fraction, but also had significantly lower rod bone volume fraction, plate trabecular number, rod trabecular number and lower plate-plate, plate-rod and rod-rod junction densities compared to Caucasian women. The differences in bone quantity and quality contributed to lower whole bone stiffness at the radius, and both whole bone and trabecular bone stiffness at the tibia in Hispanic women. In conclusion, Hispanic women had poorer bone mechanical and microarchitectural properties than Caucasian women, especially at the load bearing distal tibia. PMID- 26273527 TI - TLR signaling that induces weak inflammatory response and SHIP1 enhances osteogenic functions. AB - Toll-like receptor (TLR)-mediated inflammatory response could negatively affect bone metabolism. In this study, we determined how osteogenesis is regulated during inflammatory responses that are downstream of TLR signaling. Human primary osteoblasts were cultured in collagen gels. Pam3CSK4 (P3C) and Escherichia coli lipopolysaccharide (EcLPS) were used as TLR2 and TLR4 ligand respectively. Porphyromonas gingivalis LPS having TLR2 activity with either TLR4 agonism (Pg1690) or TLR4 antagonism (Pg1449) and mutant E. coli LPS (LPxE/LPxF/WSK) were used. IL-1beta, SH2-containing inositol phosphatase-1 (SHIP1) that has regulatory roles in osteogenesis, alkaline phosphatase and mineralization were analyzed. 3alpha-Aminocholestane (3AC) was used to inhibit SHIP1. Our results suggest that osteoblasts stimulated by P3C, poorly induced IL-1beta but strongly upregulated SHIP1 and enhanced osteogenic mediators. On the contrary, EcLPS significantly induced IL-1beta and osteogenic mediators were not induced. While Pg1690 downmodulated osteogenic mediators, Pg1449 enhanced osteogenic responses, suggesting that TLR4 signaling annuls osteogenesis even with TLR2 activity. Interestingly, mutant E. coli LPS that induces weak inflammation upregulated osteogenesis, but SHIP1 was not induced. Moreover, inhibiting SHIP1 significantly upregulated TLR2-mediated inflammatory response and downmodulated osteogenesis. In conclusion, these results suggest that induction of weak inflammatory response through TLR2 (with SHIP1 activity) and mutant TLR4 ligands could enhance osteogenesis. PMID- 26273526 TI - Bone tissue engineering via nanostructured calcium phosphate biomaterials and stem cells. AB - Tissue engineering is promising to meet the increasing need for bone regeneration. Nanostructured calcium phosphate (CaP) biomaterials/scaffolds are of special interest as they share chemical/crystallographic similarities to inorganic components of bone. Three applications of nano-CaP are discussed in this review: nanostructured calcium phosphate cement (CPC); nano-CaP composites; and nano-CaP coatings. The interactions between stem cells and nano-CaP are highlighted, including cell attachment, orientation/morphology, differentiation and in vivo bone regeneration. Several trends can be seen: (i) nano-CaP biomaterials support stem cell attachment/proliferation and induce osteogenic differentiation, in some cases even without osteogenic supplements; (ii) the influence of nano-CaP surface patterns on cell alignment is not prominent due to non-uniform distribution of nano-crystals; (iii) nano-CaP can achieve better bone regeneration than conventional CaP biomaterials; (iv) combining stem cells with nano-CaP accelerates bone regeneration, the effect of which can be further enhanced by growth factors; and (v) cell microencapsulation in nano-CaP scaffolds is promising for bone tissue engineering. These understandings would help researchers to further uncover the underlying mechanisms and interactions in nano CaP stem cell constructs in vitro and in vivo, tailor nano-CaP composite construct design and stem cell type selection to enhance cell function and bone regeneration, and translate laboratory findings to clinical treatments. PMID- 26273528 TI - Nrf2 is required for normal postnatal bone acquisition in mice. AB - A large body of literature suggests that bone metabolism is susceptible to the ill effects of reactive species that accumulate in the body and cause cellular dysfunction. One of the body's front lines in defense against such damage is the transcription factor, Nrf2. This transcription factor regulates a plethora of antioxidant and cellular defense pathways to protect cells from such damage. Despite the breadth of knowledge of both the function of Nrf2 and the effects of reactive species in bone metabolism, the direct role of Nrf2 in skeletal biology has yet to be thoroughly examined. Thus, in the current study, we have examined the role of Nrf2 in postnatal bone metabolism in mice. Mice lacking Nrf2 (Nrf2(-/ )) exhibited a marked deficit in postnatal bone acquisition, which was most severe at 3 weeks of age when osteoblast numbers were 12-fold less than observed in control animals. While primary osteoblasts from Nrf2(-/-) mice functioned normally in vitro, the colony forming capacity of bone marrow stromal cells (BMSCs) from these mice was significantly reduced compared to controls. This defect could be rescued through treatment with the radical scavenger N-acetyl cysteine (NAC), suggesting that increased reactive species stress might impair early osteoblastogenesis in BMSCs and lead to the failure of bone acquisition observed in Nrf2(-/-) animals. Taken together, these studies suggest Nrf2 represents a key pathway in regulating bone metabolism, which may provide future therapeutic targets to treat osteoporosis. PMID- 26273530 TI - New simulation model for bone formation markers in osteoporosis patients treated with once-weekly teriparatide. AB - Daily 20-MUg and once-weekly 56.5-MUg teriparatide (parathyroid hormone 1-34) treatment regimens increase bone mineral density (BMD) and prevent fractures, but changes in bone turnover markers differ between the two regimens. The aim of the present study was to explain changes in bone turnover markers using once-weekly teriparatide with a simulation model. Temporary increases in bone formation markers and subsequent decreases were observed during once-weekly teriparatide treatment for 72 weeks. These observations support the hypothesis that repeated weekly teriparatide administration stimulates bone remodeling, replacing old bone with new bone and leading to a reduction in the active remodeling surface. A simulation model was developed based on the iterative remodeling cycle that occurs on residual old bone. An increase in bone formation and a subsequent decrease were observed in the preliminary simulation. For each fitted time point, the predicted value was compared to the absolute values of the bone formation and resorption markers and lumbar BMD. The simulation model strongly matched actual changes in bone turnover markers and BMD. This simulation model indicates increased bone formation marker levels in the early stage and a subsequent decrease. It is therefore concluded that remodeling-based bone formation persisted during the entire treatment period with once-weekly teriparatide. PMID- 26273532 TI - Mechanical force enhanced bony formation in defect implanted with calcium sulphate cement. AB - To improve the osteogenic property of bone repairing materials and to accelerate bone healing are major tasks in bone biomaterials research. The objective of this study was to investigate if the mechanical force could be used to accelerate bone formation in a bony defect in vivo. The calcium sulfate cement was implanted into the left distal femoral epiphyses surgically in 16 rats. The half of rats were subjected to external mechanical force via treadmill exercise, the exercise started at day 7 postoperatively for 30 consecutive days and at a constant speed 8 m.min(-1) for 45 min.day(-1), while the rest served as a control. The rats were scanned four times longitudinally after surgery using microcomputed tomography and newly formed bone was evaluated. After sacrificing, the femurs had biomechanical test of three-point bending and histological analysis. The results showed that bone healing under mechanical force were better than the control with residual defect areas of 0.64+/-0.19 mm(2) and 1.78+/-0.39 mm(2) (P<0.001), and the ultimate loads to failure under mechanical force were 69.56+/-4.74 N, stronger than the control with ultimate loads to failure of 59.17+/-7.48 N (P=0.039). This suggests that the mechanical force might be used to improve new bone formation and potentially offer a clinical strategy to accelerate bone healing. PMID- 26273533 TI - Parathyroid hormone pulsatility: physiological and clinical aspects. AB - Parathyroid hormone (PTH) secretion is characterized by an ultradian rhythm with tonic and pulsatile components. In healthy subjects, the majority of PTH is secreted in tonic fashion, whereas approximately 30% is secreted in low-amplitude and high-frequency bursts occurring every 10-20 min, superimposed on tonic secretion. Changes in the ultradian PTH secretion were shown to occur in patients with primary and secondary osteoporosis, with skeletal effects depending on the reciprocal modifications of pulsatile and tonic components. Indeed, pathophysiology of spontaneous PTH secretion remains an area potentially suitable to be explored, particularly in those conditions such as secondary forms of osteoporosis, in which conventional biochemical and densitometric parameters may not always give reliable diagnostic and therapeutic indications. This review will highlight the literature data supporting the hypothesis that changes of ultradian PTH secretion may be correlated with skeletal fragility in primary and secondary osteoporosis. PMID- 26273531 TI - Chronic kidney disease and the skeleton. AB - Fractures across the stages of chronic kidney disease (CKD) could be due to osteoporosis, some form of renal osteodystrophy defined by specific quantitative histomorphometry or chronic kidney disease-mineral and bone disorder (CKD-MBD). CKD-MBD is a systemic disease that links disorders of mineral and bone metabolism due to CKD to either one or all of the following: abnormalities of calcium, phosphorus, parathyroid hormone or vitamin D metabolism; abnormalities in bone turnover, mineralization, volume, linear growth or strength; or vascular or other soft-tissue calcification. Osteoporosis, as defined by the National Institutes of Health, may coexist with renal osteodystrophy or CKD-MBD. Differentiation among these disorders is required to manage correctly the correct disorder to reduce the risk of fractures. While the World Health Organization (WHO) bone mineral density (BMD) criteria for osteoporosis can be used in patients with stages 1-3 CKD, the disorders of bone turnover become so aberrant by stages 4 and 5 CKD that neither the WHO criteria nor the occurrence of a fragility fracture can be used for the diagnosis of osteoporosis. The diagnosis of osteoporosis in stages 4 and 5 CKD is one of the exclusion-excluding either renal osteodystrophy or CKD-MBD as the cause of low BMD or fragility fractures. Differentiations among the disorders of renal osteodystrophy, CKD-MBD or osteoporosis are dependent on the measurement of specific biochemical markers, including serum parathyroid hormone (PTH) and/or quantitative bone histomorphometry. Management of fractures in stages 1-3 CKD does not differ in persons with or without CKD with osteoporosis assuming that there is no evidence for CKD-MBD, clinically suspected by elevated PTH, hyperphosphatemia or fibroblast growth factor 23 due to CKD. Treatment of fractures in persons with osteoporosis and stages 4 and 5 CKD is not evidence based, with the exception of post-hoc analysis suggesting efficacy and safety of specific osteoporosis therapies (alendronate, risedronate and denosumab) in stage 4 CKD. This review also discusses how to diagnose and manage fragility fractures across the five stages of CKD. PMID- 26273534 TI - Contaminated open fracture and crush injury: a murine model. AB - Modern warfare has caused a large number of severe extremity injuries, many of which become infected. In more recent conflicts, a pattern of co-infection with Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus has emerged. We attempted to recreate this pattern in an animal model to evaluate the role of vascularity in contaminated open fractures. Historically, it has been observed that infected bones frequently appear hypovascular, but vascularity in association with bone infection has not been examined in animal models. Adult rats underwent femur fracture and muscle crush injury followed by stabilization and bacterial contamination with A. baumannii complex and methicillin-resistant Staphylococcus aureus. Vascularity and perfusion were assessed by microCT angiography and SPECT scanning, respectively, at 1, 2 and 4 weeks after injury. Quantitative bacterial cultures were also obtained. Multi-bacterial infections were successfully created, with methicillin-resistant S. aureus predominating. There was overall increase in blood flow to injured limbs that was markedly greater in bacteria-inoculated limbs. Vessel volume was greater in the infected group. Quadriceps atrophy was seen in both groups, but was greater in the infected group. In this animal model, infected open fractures had greater perfusion and vascularity than non-infected limbs. PMID- 26273529 TI - High-throughput screening of mouse gene knockouts identifies established and novel skeletal phenotypes. AB - Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening (HTS) data for 3 762 distinct global gene knockout (KO) mouse lines with viable adult homozygous mice generated using either gene-trap or homologous recombination technologies. Bone mass was determined from DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from male mice at 16 weeks of age. Wild-type (WT) cagemates/littermates were examined for each gene KO. Lethality was observed in an additional 850 KO lines. Since primary HTS are susceptible to false positive findings, additional cohorts of mice from KO lines with intriguing HTS bone data were examined. Aging, ovariectomy, histomorphometry and bone strength studies were performed and possible non-skeletal phenotypes were explored. Together, these screens identified multiple genes affecting bone mass: 23 previously reported genes (Calcr, Cebpb, Crtap, Dcstamp, Dkk1, Duoxa2, Enpp1, Fgf23, Kiss1/Kiss1r, Kl (Klotho), Lrp5, Mstn, Neo1, Npr2, Ostm1, Postn, Sfrp4, Slc30a5, Slc39a13, Sost, Sumf1, Src, Wnt10b), five novel genes extensively characterized (Cldn18, Fam20c, Lrrk1, Sgpl1, Wnt16), five novel genes with preliminary characterization (Agpat2, Rassf5, Slc10a7, Slc26a7, Slc30a10) and three novel undisclosed genes coding for potential osteoporosis drug targets. PMID- 26273535 TI - Disruption of bone and skeletal muscle in severe burns. AB - Severe burn injury triggers the body's nonspecific adaptive responses to acute insult, including the systemic inflammatory and stress responses, as well as the sympathetic response to immobilization. These responses trigger inflammatory bone resorption followed by glucocorticoid-induced apoptosis of osteoblasts and probably osteocytes. Because these patients are catabolic, they suffer concomitant muscle wasting and negative nitrogen balance. The use of anabolic agents such as recombinant human growth hormone and oxandrolone results in improved bone mineral content and muscle strength after approximately 1 year. Use of bisphosphonates within the first 10 days of a severe burn completely blocks the resorptive bone loss and has the added advantage of appearing to preserve muscle protein from excessive breakdown. The mechanism for the protective effect on muscle is not currently known. However, if the effect of bisphosphonates on muscle can be confirmed, it raises the possibility that bone communicates with muscle. PMID- 26273536 TI - Decreased osteogenesis of adult mesenchymal stem cells by reactive oxygen species under cyclic stretch: a possible mechanism of age related osteoporosis. AB - Age related defect of the osteogenic differentiation of mesenchymal stem cells (MSCs) plays a key role in osteoporosis. Mechanical loading is one of the most important physical stimuli for osteoblast differentiation. Here, we compared the osteogenic potential of MSCs from young and adult rats under three rounds of 2 h of cyclic stretch of 2.5% elongation at 1 Hz on 3 consecutive days. Cyclic stretch induced a significant osteogenic differentiation of MSCs from young rats, while a compromised osteogenesis in MSCs from the adult rats. Accordingly, there were much more reactive oxygen species (ROS) production in adult MSCs under cyclic stretch compared to young MSCs. Moreover, ROS scavenger N-acetylcysteine rescued the osteogenic differentiation of adult MSCs under cyclic stretch. Gene expression analysis revealed that superoxide dismutase 1 (SOD1) was significantly downregulated in those MSCs from adult rats. In summary, our data suggest that reduced SOD1 may result in excessive ROS production in adult MSCs under cyclic stretch, and thus manipulation of the MSCs from the adult donors with antioxidant would improve their osteogenic ability. PMID- 26273538 TI - Axial strain enhances osteotomy repair with a concomitant increase in connexin43 expression. AB - The mechanical environment is known to influence fracture healing. We speculated that connexin43 (Cx43) gap junctions, which impact skeletal homeostasis, fracture healing and the osteogenic response to mechanical load, may play a role in mediating the response of the healing bone to mechanical strain. Here, we used an established rat fracture model, which uses a 2 mm osteotomy gap stabilized by an external fixator, to examine the impact of various cyclical axial loading protocols (2%, 10%, and 30% strain) on osteotomy healing. We examined the presence of Cx43 in the osteotomy-healing environment and assessed how mechanical strain modulates Cx43 expression patterns in the callus. We demonstrated that increased cyclical axial strain results in increased radiographic and histologic bone formation. In addition, we show by immunohistochemistry that Cx43 is abundantly expressed in the healing callus, with the expression most robust in samples exposed to increased cyclical axial strain. These data are consistent with the concept that an increase in Cx43 expression by mechanical load may be part of the mechanisms by which mechanical forces enhances fracture healing. PMID- 26273539 TI - The effect of the fibre orientation of electrospun scaffolds on the matrix production of rabbit annulus fibrosus-derived stem cells. AB - Annulus fibrosus (AF) tissue engineering has recently received increasing attention as a treatment for intervertebral disc (IVD) degeneration; however, such engineering remains challenging because of the remarkable complexity of AF tissue. In order to engineer a functional AF replacement, the fabrication of cell scaffold constructs that mimic the cellular, biochemical and structural features of native AF tissue is critical. In this study, we fabricated aligned fibrous polyurethane scaffolds using an electrospinning technique and used them for culturing AF-derived stem/progenitor cells (AFSCs). Random fibrous scaffolds, also prepared via electrospinning, were used as a control. We compared the morphology, proliferation, gene expression and matrix production of AFSCs on aligned scaffolds and random scaffolds. There was no apparent difference in the attachment or proliferation of cells cultured on aligned scaffolds and random scaffolds. However, compared to cells on random scaffolds, the AFSCs on aligned scaffolds were more elongated and better aligned, and they exhibited higher gene expression and matrix production of collagen-I and aggrecan. The gene expression and protein production of collagen-II did not appear to differ between the two groups. Together, these findings indicate that aligned fibrous scaffolds may provide a favourable microenvironment for the differentiation of AFSCs into cells similar to outer AF cells, which predominantly produce collagen-I matrix. PMID- 26273537 TI - TGF-beta/BMP signaling and other molecular events: regulation of osteoblastogenesis and bone formation. AB - Transforming growth factor-beta (TGF-beta)/bone morphogenetic protein (BMP) plays a fundamental role in the regulation of bone organogenesis through the activation of receptor serine/threonine kinases. Perturbations of TGF-beta/BMP activity are almost invariably linked to a wide variety of clinical outcomes, i.e., skeletal, extra skeletal anomalies, autoimmune, cancer, and cardiovascular diseases. Phosphorylation of TGF-beta (I/II) or BMP receptors activates intracellular downstream Smads, the transducer of TGF-beta/BMP signals. This signaling is modulated by various factors and pathways, including transcription factor Runx2. The signaling network in skeletal development and bone formation is overwhelmingly complex and highly time and space specific. Additive, positive, negative, or synergistic effects are observed when TGF-beta/BMP interacts with the pathways of MAPK, Wnt, Hedgehog (Hh), Notch, Akt/mTOR, and miRNA to regulate the effects of BMP-induced signaling in bone dynamics. Accumulating evidence indicates that Runx2 is the key integrator, whereas Hh is a possible modulator, miRNAs are regulators, and beta-catenin is a mediator/regulator within the extensive intracellular network. This review focuses on the activation of BMP signaling and interaction with other regulatory components and pathways highlighting the molecular mechanisms regarding TGF-beta/BMP function and regulation that could allow understanding the complexity of bone tissue dynamics. PMID- 26273540 TI - (99m)TC-Methylene diphosphonate uptake at injury site correlates with osteoblast differentiation and mineralization during bone healing in mice. AB - (99m)Tc-Methylene diphosphonate ((99m)Tc-MDP) is widely used in clinical settings to detect bone abnormalities. However, the mechanism of (99m)Tc-MDP uptake in bone is not well elucidated. In this study, we utilized a mouse tibia injury model, single-photon emission computed tomography (gamma scintigraphy or SPECT), ex vivo micro-computed tomography, and histology to monitor (99m)Tc-MDP uptake in injury sites during skeletal healing. In an ex vivo culture system, calvarial cells were differentiated into osteoblasts with osteogenic medium, pulsed with (99m)Tc-MDP at different time points, and quantitated for (99m)Tc-MDP uptake with a gamma counter. We demonstrated that (99m)Tc-MDP uptake in the injury sites corresponded to osteoblast generation in those sites throughout the healing process. The (99m)Tc-MDP uptake within the injury sites peaked on day 7 post injury, while the injury sites were occupied by mature osteoblasts also starting from day 7. (99m)Tc-MDP uptake started to decrease 14 days post-surgery, when we observed the highest level of bony tissue in the injury sites. We also found that (99m)Tc-MDP uptake was associated with osteoblast maturation and mineralization in vitro. This study provides direct and biological evidence for (99m)Tc-MDP uptake in osteoblasts during bone healing in vivo and in vitro. PMID- 26273542 TI - Did the "Woman in the Attic" in Jane Eyre Have Huntington Disease? AB - BACKGROUND: References to neurologic disorders are frequently found in fictional literature and may precede description in the medical literature. AIM: Our aim was to compare Charlotte Bronte's depiction of Bertha Mason in Jane Eyre to the tenets set forth in George Huntington's original essay "On chorea" with the hypothesis that Mason was displaying features of Huntington disease. RESULTS: Charlotte Bronte's 1847 Victorian novel Jane Eyre features the character Bertha Mason, who is portrayed with a progressive psychiatric illness, violent movements, and possible cognitive decline. Similar to Huntington's tenets, Mason has a disorder with a strong family history suggestive of autosomal dominant inheritance with onset in adulthood, and culminating in suicide. CONCLUSION: Bronte's character had features of Huntington disease as originally described by Huntington. Bronte's keen characterization may have increased awareness of treatment of neuropsychiatric patients in the Victorian era. PMID- 26273541 TI - Contemporary approaches for imaging skeletal metastasis. AB - The skeleton is a common site of cancer metastasis. Notably high incidences of bone lesions are found for breast, prostate, and renal carcinoma. Malignant bone tumors result in significant patient morbidity. Identification of these lesions is a critical step to accurately stratify patients, guide treatment course, monitor disease progression, and evaluate response to therapy. Diagnosis of cancer in the skeleton typically relies on indirect bone-targeted radiotracer uptake at sites of active bone remodeling. In this manuscript, we discuss established and emerging tools and techniques for detection of bone lesions, quantification of skeletal tumor burden, and current clinical challenges. PMID- 26273543 TI - Evidence that Human Prostate Cancer is a ZIP1-Deficient Malignancy that could be Effectively Treated with a Zinc Ionophore (Clioquinol) Approach. AB - Despite decades of research, no efficacious chemotherapy exists for the treatment of prostate cancer. Malignant prostate zinc levels are markedly decreased in all cases of prostate cancer compared to normal/benign prostate. ZIP1 zinc transporter down regulation decreases zinc to prevent its cytotoxic effects. Thus, prostate cancer is a "ZIP1-deficient" malignancy. A zinc ionophore (e.g. Clioquinol) treatment to increase malignant zinc levels is a plausible treatment of prostate cancer. However, skepticism within the clinical/biomedical research community impedes significant progress leading to such a zinc treatment. This report reviews the clinical and experimental background, and presents new experimental data showing Clioquinol suppression of prostate malignancy; which provides strong support for a zinc ionophore treatment for prostate cancer. Evaluation of often-raised opposing issues is presented. These considerations lead to the conclusion that the compelling evidence dictates that a zinc treatment approach for prostate cancer should be pursued with additional research leading to clinical trials. PMID- 26273546 TI - Cost-effectiveness of three treatment strategies for lumbar spinal stenosis: Conservative care, laminectomy, and the Superion interspinous spacer. AB - BACKGROUND: Lumbar spinal stenosis is a painful and debilitating condition resulting in healthcare costs totaling tens of billions of dollars annually. Initial treatment consists of conservative care modalities such as physical therapy, NSAIDs, opioids, and steroid injections. Patients refractory to these therapies can undergo decompressive surgery, which has good long-term efficacy but is more traumatic and can be associated with high post-operative adverse event (AE) rates. Interspinous spacers have been developed to offer a less invasive alternative. The objective of this study was to compare the costs and quality adjusted life years (QALYs) gained of conservative care (CC) and decompressive surgery (DS) to a new minimally-invasive interspinous spacer. METHODS: A Markov model was developed evaluating 3 strategies of care for lumbar spinal stenosis. If initial therapies failed, the model moved patients to more invasive therapies. Data from the Superion FDA clinical trial, a prospective spinal registry, and the literature were used to populate the model. Direct medical care costs were modeled from 2014 Medicare reimbursements for healthcare services. QALYs came from the SF-12 PCS and MCS components. The analysis used a 2 year time horizon with a 3% discount rate. RESULTS: CC had the lowest cost at $10,540, while Spacers and DS were nearly identical at about $13,950. CC also had the lowest QALY increase (0.06), while Spacers and DS were again nearly identical (.28). The incremental cost-effectiveness ratios (ICER) for Spacers compared to CC was $16,300 and for DS was $15,200. CONCLUSIONS: Both the Spacer and DS strategies are far below the commonly cited $50,000/QALY threshold and produced several times the QALY increase versus CC, suggesting that surgical care provides superior value (cost / effectiveness) versus sustained conservative care in the treatment of lumbar spinal stenosis. PMID- 26273544 TI - Brain Imaging in Gambling Disorder. AB - Gambling disorder recently was reclassified under the category "substance-related and addictive disorders." With regard to the diagnostic criteria, it overlaps a great deal with substance use disorder, i.e., loss of control, craving/withdrawal, and neglect of other areas of life. However, the gambling disorder symptom "chasing one's losses" is the only criterion absent from substance use disorder. Therefore, special forms of reward (i.e., gain/loss) processing, such as the processing of loss avoidance and loss aversion, have just recently attracted attention among gambling disorder researchers. Because gambling disorder might be considered an addiction in its "pure" form, i.e., without the influence of a drug of abuse, investigating brain volume changes in people with this behavioral addiction is an important task for neuroimaging researchers in exploring the neural signatures of addiction. Because the brain is a complex network, investigation of alterations in functional connectivity has gained interest among gambling disorder researchers in order to get a more complete picture of functional brain changes in people with gambling disorder. However, only a few studies on brain structure and functional connectivity in gambling disorder have been performed so far. This review focuses on brain imaging studies of reward and loss processing, with an emphasis on loss avoidance and aversion as well as brain volume and functional connectivity in gambling disorder. PMID- 26273547 TI - Remote Cerebellar Hemorrhage Complicating Unintended Durotomy in Lumbar Spine Surgery. AB - STUDY DESIGN: Case reports and retrospective review of accidental durotomies in lumbar surgeries during 5 years. OBJECTIVES: To draw attention to a potentially serious complication of incidental durotomy-remote cerebellar hemorrhage. SUMMARY AND BACKGROUND DATA: Accidental durotomy is a frequent complication of spinal surgery. In most cases the outcome of incidental durotomy is favorable. A delayed potentially serious complication of CSF loss during and after lumbar surgery is remote cerebellar hemorrhage (RCH). METHODS: During 2008-2012, 1169 lumbar spine procedures were performed at our spine center. In 210 surgeries incidental or intentional durotomies occurred. All patients with durotomies were managed with suturing of the dural wound followed by deep wound drainage left for 5 days and tight wound closure. RESULTS: Of the 210 patients with CSF loss three patients were identified to suffer from RCH-an incidence of 0.26%. The three patients ages 56, 67 and 75 years developed RCH between 36-192 hours after surgery. All three were managed with supportive treatment and close clinical supervision. A gradual clinical and radiological improvement was noted in all three patients. CONCLUSIONS: Severe headache after spinal surgery and or declining mental status should not be attributed only to low CSF pressure secondary to dural tearing. It can also be the result of remote cerebral or cerebellar hemorrhage. Once the diagnosis of RCH is made, close clinical supervision is mandatory. In most cases non-operative supportive treatment may lead to eventual full clinical recovery. PMID- 26273545 TI - Cruciferous vegetables, isothiocyanates, and prevention of bladder cancer. AB - Approximately 80% of human bladder cancers (BC) are non-muscle invasive when first diagnosed and are usually treated by transurethral tumor resection. But 50 80% of patients experience cancer recurrence. Agents for prevention of primary BC have yet to be identified. Existing prophylactics against BC recurrence, e.g., Bacillus Calmette-Guerin (BCG), have limited efficacy and utility; they engender significant side effects and require urethral catheterization. Many cruciferous vegetables, rich sources of isothiocyanates (ITCs), are commonly consumed by humans. Many ITCs possess promising chemopreventive activities against BC and its recurrence. Moreover, orally ingested ITCs are selectively delivered to bladder via urinary excretion. This review is focused on urinary delivery of ITCs to the bladder, their cellular uptake, their chemopreventive activities in preclinical and epidemiological studies that are particularly relevant to prevention of BC recurrence and progression, and their chemopreventive mechanisms in BC cells and tissues. PMID- 26273548 TI - Assessment of Magnetic Resonance Imaging Artifact Following Cervical Total Disc Arthroplasty. AB - BACKGROUND: Cervical disc arthroplasty has become a technique for the treatment of cervical degenerative disc disease. Clinically, the need to accurately assess the neural elements at the operative and adjacent levels is critical postoperatively. The purpose of this study was to quantitatively and qualitatively measure the amount of MRI artifact produced by various cervical total disc replacements. METHODS: T1 and T2-weighted turbo spin-echo MRI sequences were collected on the cervical spine (C2-T1) of a 68 year-old unembalmed male cadaver. A discectomy was performed at C5-6, followed by successive implantation of six different total disc replacements. The scans were quantitatively evaluated by three of the authors. The volume of artifact was measured using image analysis software. Qualitative analysis of the adjacent and index neural elements was performed. RESULTS: The artifact in the T2 weighted images was noted to be 58.6+/-7.3 cm3 for Prestige ST, 14.2+/-1.3 cm3 for ProDisc C, 7.5+/-0.8 cm3 for Discover, 8.0+/-0.3 cm3 for Prestige LP, 6.6+/-0.7 cm3 for Bryan, and 7.3+/-0.6 cm3 for ProDisc-C titanium prototype. Acceptable intraobserver and excellent interobsever correlation was demonstrated using Pearson Correlation and Concordance Correlation Coefficient analysis. The adjacent and implanted level neural elements (spinal cord and neuroforamina) were easily visualized on the T2 weighted images after the implantation of titanium devices (ProDisc-C titanium prototype, Discover, Prestige LP and Bryan). After implantation of a cobalt chrome implant (ProDisc-C), the adjacent level neural elements were easily visualized but the implanted level could not be fully visualized due to distortion of the images. The quality of the distortion was least favorable after the implantation of the stainless steel implant (Prestige ST), where neither the adjacent nor the index level could be fully visualized. CONCLUSION: The volume of the artifact seen following cervical total disc arthroplasty is highly dependent upon the material property of the implant. Quantitative analysis described in this study demonstrated sufficiently low intraobserver and interobserver variability to be considered a reliable technique. PMID- 26273549 TI - Foreword, Biomechanics Special Issue. PMID- 26273550 TI - Comparison of Intervertebral ROM in Multi-Level Cadaveric Lumbar Spines Using Distinct Pure Moment Loading Approaches. AB - BACKGROUND: Pure-moment loading is the test method of choice for spinal implant evaluation. However, the apparatuses and boundary conditions employed by laboratories in performing spine flexibility testing vary. The purpose of this study was to quantify the differences, if they exist, in intervertebral range of motion (ROM) resulting from different pure-moment loading apparatuses used in two laboratories. METHODS: Twenty-four (laboratory A) and forty-two (laboratory B) intact L1-S1 specimens were loaded using pure moments (+/-7.5 Nm) in flexion extension (FE), lateral bending (LB) and axial torsion (AT). At laboratory A, pure moments were applied using a system of cables, pulleys and suspended weights in 1.5 Nm increments. At laboratory B, specimens were loaded in a pneumatic biaxial test frame mounted with counteracting stepper-motor-driven biaxial gimbals. ROM was obtained in both labs using identical optoelectronic systems and compared. RESULTS: In FE, total L1-L5 ROM was similar, on average, between the two laboratories (lab A: 37.4 degrees +/- 9.1 degrees ; lab B: 35.0 degrees +/- 8.9 degrees , p=0.289). Larger apparent differences, on average, were noted between labs in AT (lab A: 19.4 degrees +/- 7.3 degrees ; lab B: 15.7 degrees +/- 7.1 degrees , p=0.074), and this finding was significant for combined right and left LB (lab A: 45.5 degrees +/- 11.4 degrees ; lab B: 35.3 degrees +/- 8.5 degrees , p < 0.001). CONCLUSIONS: To our knowledge, this is the first study comparing ROM of multi-segment lumbar spines between laboratories utilizing different apparatuses. The results of this study show that intervertebral ROM in multi-segment lumbar spine constructs are markedly similar in FE loading. Differences in boundary conditions are likely the source of small and sometimes statistically significant differences between the two techniques in LB and AT ROM. The relative merits of each testing strategy with regard to the physiologic conditions that are to be simulated should be considered in the design of a study including LB and AT modes of loading. An understanding of these differences also serves as important information when comparing study results across different laboratories. PMID- 26273551 TI - Biomechanical Comparison of Robotically Applied Pure Moment, Ideal Follower Load, and Novel Trunk Weight Loading Protocols on L4-L5 Cadaveric Segments during Flexion-Extension. AB - BACKGROUND: Extremely few in-vitro biomechanical studies have incorporated shear loads leaving a gap for investigation, especially when applied in combination with compression and bending under dynamic conditions. The objective of this study was to biomechanically compare sagittal plane application of two standard protocols, pure moment (PM) and follower load (FL), with a novel trunk weight (TW) loading protocol designed to induce shear in combination with compression and dynamic bending in a neutrally potted human cadaveric L4-L5 motion segment unit (MSU) model. A secondary objective and novelty of the current study was the application of all three protocols within the same testing system serving to reduce artifacts due to testing system variability. METHODS: Six L4-L5 segments were tested in a Cartesian load controlled system in flexion-extension to 8Nm under PM, simulated ideal 400N FL, and vertically oriented 400N TW loading protocols. Comparison metrics used were rotational range of motion (RROM), flexibility, neutral zone (NZ) range of motion, and L4 vertebral body displacements. RESULTS: Significant differences in vertebral body translations were observed with different initial force applications but not with subsequent bending moment application. Significant reductions were observed in combined flexion-extension RROM, in flexibility during extension, and in NZ region flexibility with the TW loading protocol as compared to PM loading. Neutral zone ranges of motion were not different between all protocols. CONCLUSIONS: The combined compression and shear forces applied across the spinal joint in the trunk weight protocol may have a small but significantly increased stabilizing effect on segment flexibility and kinematics during sagittal plane flexion and extension. PMID- 26273553 TI - Fine grained osseointegrative coating improves biocompatibility of PEEK in heterotopic sheep model. AB - BACKGROUND AND AIM: Polyetheretherketone (PEEK) materials already have been used successfully in orthopedic and especially spine surgery. PEEK is radiolucent and comparable with bone regarding elasticity. However, PEEK is inert and the adhesion of PEEK implants to bone tissue proceeds slowly because of their relatively low biocompatibility. The aim of the study is to evaluate the effect of titanium and CaP coating on the adhesion of bone tissue. MATERIAL AND METHODS: Six adult sheep (body weight 57.6 +/- 3.9 kg) were included in this study. Three different types of cylindrical dowels (12 mm length x 8 mm diameter) were implanted in long bones (tibia and femur): PEEK dowels without coating (the control group), and PEEK dowels with a nanocoating of calcium phosphate (CaP group) or titanium (titanium group). Animals were sacrificed after 6, 12 and 26 weeks. Dowels were explanted for micro CT and histology. RESULTS: Bone implant contact (BIC) ratio was significantly higher in the titanium versus control groups in the 6 to 12 weeks period (p = 0.03). The ratio between bone volume and tissue volume (BV/TV) was significantly higher in titanium versus control in the 6 to 12 weeks period (p = 0.02). A significant correlation between BIC and BV/TV was seen (r = 0.85, p < 0.05). CONCLUSION: Coating of PEEK dowels with a nanocoating of titanium has beneficial effects on adhesion of bone tissue. PMID- 26273554 TI - Measurement Performance of a Computer Assisted Vertebral Motion Analysis System. AB - BACKGROUND: Segmental instability of the lumbar spine is a significant cost within the US health care system; however current thresholds for indication of radiographic instability are not well defined. PURPOSE: To determine the performance measurements of sagittal lumbar intervertebral measurements using computerassisted measurements of the lumbar spine using motion sequences from a video-fluoroscopic technique. STUDY DESIGN: Sensitivity, specificity, predictive values, prevalence, and test-retest reliability evaluation of digitized manual versus computer-assisted measurements of the lumbar spine. PATIENT SAMPLE: A total of 2239 intervertebral levels from 509 symptomatic patients, and 287 intervertebral levels from 73 asymptomatic participants were retrospectively evaluated. OUTCOME MEASURES: Specificity, sensitivity, negative predictive value (NPV), diagnostic accuracy, and prevalence between the two measurement techniques; Measurements of Coefficient of repeatability (CR), limits of agreement (LOA), intraclass correlation coefficient (ICC; type 3,1), and standard error of measurement for both measurement techniques. METHODS: Asymptomatic individuals and symptomatic patients were all evaluated using both the Vertebral Motion Analysis (VMA) system and fluoroscopic flexion extension static radiographs (FE). The analysis was compared to known thresholds of 15% intervertebral translation (IVT, equivalent to 5.3mm assuming a 35mm vertebral body depth) and 25 degrees intervertebral rotation (IVR). RESULTS: The VMA measurements demonstrated greater specificity, % change in sensitivity, NPV, prevalence, and reliability compared with FE for radiographic evidence of instability. Specificity was 99.4% and 99.1% in the VMA compared to 98.3% and 98.2% in the FE for IVR and IVT, respectively. Sensitivity in this study was 41.2% and 44.6% greater in the VMA compared to the FE for IVR and IVT, respectively. NPV was 91% and 88% in the VMA compared to 62% and 66% in the FE for IVR and IVT, respectively. Prevalence was 12.3% and 11.9% for the VMA compared to 6.1% and 5.4% for the FE in IVR and IVT, respectively. Intra-observer IVR and IVT had a CR of 2.49 and 2.62, respectively. Inter-observer IVR and IVT had a CR of 1.99 and 2.81, respectively. Intra-subject (test/retest) CR were 2.49 and 3.11 for IVR and IVT, respectively. CONCLUSIONS: The VMA system showed greater measurement performance in the detection of radiographic instability compared with FE radiographs. PMID- 26273552 TI - Advanced Multi-Axis Spine Testing: Clinical Relevance and Research Recommendations. AB - Back pain and spinal degeneration affect a large proportion of the general population. The economic burden of spinal degeneration is significant, and the treatment of spinal degeneration represents a large proportion of healthcare costs. However, spinal surgery does not always provide improved clinical outcomes compared to non-surgical alternatives, and modern interventions, such as total disc replacement, may not offer clinically relevant improvements over more established procedures. Although psychological and socioeconomic factors play an important role in the development and response to back pain, the variation in clinical success is also related to the complexity of the spine, and the multi faceted manner by which spinal degeneration often occurs. The successful surgical treatment of degenerative spinal conditions requires collaboration between surgeons, engineers, and scientists in order to provide a multi-disciplinary approach to managing the complete condition. In this review, we provide relevant background from both the clinical and the basic research perspectives, which is synthesized into several examples and recommendations for consideration in increasing translational research between communities with the goal of providing improved knowledge and care. Current clinical imaging, and multi-axis testing machines, offer great promise for future research by combining invivo kinematics and loading with in-vitro testing in six degrees of freedom to offer more accurate predictions of the performance of new spinal instrumentation. Upon synthesis of the literature, it is recommended that in-vitro tests strive to recreate as many aspects of the in-vivo environment as possible, and that a physiological preload is a critical factor in assessing spinal biomechanics in the laboratory. A greater link between surgical procedures, and the outcomes in all three anatomical planes should be considered in both the in-vivo and in-vitro settings, to provide data relevant to quality of motion, and stability. PMID- 26273555 TI - Development of a novel radiographic measure of lumbar instability and validation using the facet fluid sign. AB - BACKGROUND: Lumbar spinal instability is frequently referenced in clinical practice and the scientific literature despite the lack of a standard definition or validated radiographic test. The Quantitative Stability Index (QSI) is being developed as a novel objective test for sagittal plane lumbar instability. The QSI is calculated using lumbar flexion-extension radiographs. The goal of the current study was to use the facet fluid sign on MRI as the "gold standard" and determine if the QSI is significantly different in the presence of the fluid sign. METHODS: Sixty-two paired preoperative MRI and flexion-extension exams were obtained from a large FDA IDE study. The MRI exams were assessed for the presence of a facet fluid sign, and the QSI was calculated from sagittal plane intervertebral rotation and translation measurements. The QSI is based on the translation per degree of rotation (TPDR) and is calculated as a Z-score. A QSI > 2 indicates that the TPDR is > 2 std dev above the mean for an asymptomatic and radiographically normal population. The reproducibility of the QSI was also tested. RESULTS: The mean difference between trained observers in the measured QSI was between -0.28 and 0.36. The average QSI was significantly (P = 0.047, one way analysis of variance) higher at levels with a definite fluid sign (2.3+/-3.2 versus 0.60+/-2.4). CONCLUSIONS: Although imperfect, the facet fluid sign observed may be the best currently available test for lumbar spine instability. Using the facet fluid sign as the "gold standard" the current study documents that the QSI can be expected to be significantly higher in the presence of the facet fluid sign. This supports that QSI might be used to test for sagittal plane lumbar instability. CLINICAL RELEVANCE: A validated, objective and practical test for spinal instability would facilitate research to understand the importance of instability in diagnosis and treatment of low-back related disorders. PMID- 26273556 TI - Effect of TLIF Cage Placement on In Vivo Kinematics. AB - BACKGROUND: The influence of interbody cage positioning on clinical outcomes following lumbar interbody fusion is not well understood, though it has been hypothesized to play a significant role in stability of the treated level. The purpose of this study was to evaluate any correlations between cage placement in TLIF procedures and post-operative kinematics. METHODS: Thirteen patients who had previously undergone a TLIF procedure were evaluated using the Vertebral Motion Analysis (VMA) system, an automated fluoroscopic method of tracking kinematics in vivo. Upright and recumbent bending platforms were used to guide patients through a set range of motion (ROM) standing up and lying down, respectively, in both flexion-extension (FE) and lateral bending (LB). Intervertebral ROM was measured via fluoroscopic images captured sequentially throughout the movement. DICOM images acquired by the VMA system were used to calculate cage positioning. Intra rater and inter-rater reliability of TLIF cage position were also assessed. RESULTS: Statistically significant correlations were noted between sagittal cage position and lying LB (r = -0.583, p = 0.047), and coronal cage positioning with both standing (r = 0.672, p = 0.012) and lying LB (r = 0.632, p = 0.027). Additionally, the correlation between sagittal cage position and standing FE was trending towards significance (r = -0.542, p = 0.055). CONCLUSIONS: The intuitive correlation between coronal cage position and both standing and lying lateral bending ROM is supported by the data from this study, suggesting placement closer to midline is optimal for stability. Additionally, the VMA system appears to be a sensitive and repeatable means to obtain information on postoperative kinematic outcomes. Further work to establish the relationship between cage placement, these kinematic outcomes and, potentially, functional pain outcomes seems to be warranted based on the results obtained here. PMID- 26273557 TI - Early Radiographic and Clinical Outcomes Study Evaluating an Integrated Screw and Interbody Spacer for One- and Two-Level ACDF. AB - BACKGROUND: Multiple techniques and implants can be used in ACDF, the newest of which are integrated cage and screw constructs. These devices may be beneficial over anterior plate constructs due to a negligible anterior profile that may reduce dysphagia. The goal of this study is to review the early radiographical and clinical results associated with a low profile integrated intervertebral cage in one- and two-level anterior column fusions. METHODS: Fusion rates, incidence of hardware failure and deformity correction were assessed through 1 year. Patientreported scores, including VAS for neck pain, and improvements in axial neck pain and neurologic deficit from the preoperative baseline were quantified at 3, 6 and 12 months post-operatively. The incidence of dysphagia was recorded. RESULTS: Lordosis and disc space height at the operated levels increased an average of 4.5 degrees and 3.3mm after device placement (p<0.001). Sagittal plane correction was maintained at 1 year. VAS improved from an average of 5.1 preoperatively to 3.1 immediately postoperatively and was maintained at 12 months. At 3 months, patient-reported improvements in axial neck pain and neurologic deficit were 85% and 93%, respectively. Reported improvements were sustained for both parameters at 12 months (77% and 86%, respectively). Fusion was noted in 93% of the operated levels. There were two documented cases of dysphagia that lasted more than 5 weeks, both following two level ACDFs with the test device (3.5% rate of chronic dysphagia). CONCLUSIONS: The low profile integrated device improved lordosis at the operated level that was maintained at 1 year. Fusion rates with the new device are consistent with ACDF using anterior plating. In combination with improvements in pain and a minimal rate of dysphagia, study findings support the use of integrated interbody spacers for use in one- and two-level ACDF procedures. LEVEL OF EVIDENCE: Level IV, Case Series. PMID- 26273558 TI - A systematic review of minimally invasive sacroiliac joint fusion utilizing a lateral transarticular technique. AB - BACKGROUND: A number of studies have been published regarding minimally invasive surgical (MIS) fusion of the sacroiliac (SI) joint using a lateral transarticular approach. Herein we report a systematic review and meta-analysis to summarize operative measures and clinical outcomes reported in published studies of MIS SI joint fusion. METHODS: The systematic review was done according to PRISMA standards. PubMed and EMBASE were searched using the terms sacroiliac joint AND fusion. Original peer-reviewed articles in the English language that reported clinical outcomes on at least 5 cases of MIS SI joint fusion using a lateral transarticular approach were included. Random effects meta-analysis (RMA) was performed on selected variables using the DerSimonian and Laird method, including operative measures, VAS SI joint pain ratings (0-10 scale) and Oswestry Disability Index (ODI). Mean and 95% confidence intervals (CI) were calculated and heterogeneity was assessed. Other findings were summarized qualitatively. RESULTS: A total of 18 articles met the inclusion criteria. After accounting for overlapping cohorts, 12 unique cohorts from 4 countries were extracted for a total of 432 subjects. The RMA mean (range) was 59 minutes (27-78) for procedure time, 36.9cc (10-70) for estimated blood loss and 1.7 days (range 0-7) for length of stay (LOS). The RMA mean [95% CI] pain score dropped by 5.2 points at 6 months and 5.3 points at 12 months (baseline score of 8.1 [7.8-8.4], 12-month score of 2.7 [2.1-3.3]), and a 24-month score of 2.0(1.4-2.5). ODI decreased by 31 points at 12 months (baseline score of 56.2 [51.0-61.5], 6-month score of 30.7 [21.8 39.6], and 12-month score of 25.1 [12.3-37.9]). Some estimates showed significant variation across studies and between the types of implants used. Other reported outcomes were supportive of the positive effects of SI joint fusion. CONCLUSION: Published studies of MIS SI joint fusion using a lateral transarticular approach confirm its minimally invasive characteristics with minimal blood loss and short operating room times, and show consistent, rapid, sustained and clinically important improvements in patient reported SI joint pain, disability and quality of life scores. PMID- 26273559 TI - An HcpR paralog of Desulfovibrio gigas provides protection against nitrosative stress. AB - Desulfovibrio gigas belongs to the group of sulfate reducing bacteria (SRB). These ubiquitous and metabolically versatile microorganisms are often exposed to reactive nitrogen species (RNS). Nonetheless, the mechanisms and regulatory elements involved in nitrosative stress protection are still poorly understood. The transcription factor HcpR has emerged as a putative regulator of nitrosative stress response among anaerobic bacteria. HcpR is known to orchestrate the expression of the hybrid cluster protein gene, hcp, proposed to be involved in cellular defense against RNS. According to phylogenetic analyses, the occurrence of hcpR paralog genes is a common feature among several Desulfovibrio species. Within the D. gigas genome we have identified two HcpR-related sequences. One of these sequences, hcpR1, was found in the close vicinity of the hcp gene and this finding prompted us to proceed with its functional characterization. We observed that the growth of a D. gigas strain lacking hcpR1 is severely impaired under nitrosative stress. An in silico search revealed several putative targets of HcpR1 that were experimentally validated. The fact that HcpR1 regulates several genes encoding proteins involved in nitrite and nitrate metabolism, together with the sensitive growth phenotype to NO displayed by an hcpR1 mutant strain, strongly supports a relevant role of this factor under nitrosative stress. Moreover, the finding that several Desulfovibrio species possess HcpR paralogs, which have been transmitted vertically in the evolution and diversification of the genus, suggests that these sequences may confer adaptive or survival advantage to these organisms, possibly by increasing their tolerance to nitrosative stress. PMID- 26273560 TI - Proteasome inhibitors prevent cell death and prolong survival of mice challenged by Shiga toxin. AB - Shiga toxin (Stx) causes fatal systemic complications. Stx induces apoptosis, but the mechanism of which is unclear. We report that Stx induced rapid reduction of short-lived anti-apoptotic proteins followed by activation of caspase 9 and the progression of apoptosis. Proteasome inhibitors prevented the reduction of anti apoptotic proteins, and inhibited caspase activation and apoptosis, suggesting that the reduction of anti-apoptotic proteins is a prerequisite for Stx-induced apoptosis. A clinically approved proteasome inhibitor, bortezomib, prolonged the survival of mice challenged by Stx. These results imply that proteasome inhibition may be a novel approach to prevent the fatal effects of Stx. PMID- 26273561 TI - Plasma treatment of dentin surfaces for improving self-etching adhesive/dentin interface bonding. AB - This study is to evaluate plasma treatment effects on dentin surfaces for improving self-etching adhesive and dentin interface bonding. Extracted unerupted human third molars were used after crown removal to expose dentin. One half of each dentin surface was treated with atmospheric non-thermal argon plasmas, while another half was untreated and used as the same tooth control. Self-etching adhesive and universal resin composite was applied to the dentin surfaces as directed. After restoration, the adhesive-dentin bonding strength was evaluated by micro-tensile bonding strength (MUTBS) test. Bonding strength data was analyzed using histograms and Welch's t-test based on unequal variances. MUTBS test results showed that, with plasma treatment, the average MUTBS value increased to 69.7+/-11.5 MPa as compared with the 57.1+/-17.5 MPa obtained from the untreated controls. After 2 months immersion of the restored teeth in 37 degrees C phosphate buffered saline (PBS), the adhesive-dentin bonding strengths of the plasma-treated specimens slightly decreased from 69.7+/-11.5 MPa to 63.9+/ 14.4 MPa, while the strengths of the untreated specimens reduced from 57.1+/-17.5 MPa to 48.9+/-14.6 MPa. Water contact angle measurement and scanning electron microscopy (SEM) examination verified that plasma treatment followed by water rewetting could partially open dentin tubules, which could enhance adhesive penetration to form thicker hybrid layer and longer resin tags and consequently improve the adhesive/dentin interface quality. PMID- 26273562 TI - Mutation rate estimation for 15 autosomal STR loci in a large population from Mainland China. AB - STR, short tandem repeats, are well known as a type of powerful genetic marker and widely used in studying human population genetics. Compared with the conventional genetic markers, the mutation rate of STR is higher. Additionally, the mutations of STR loci do not lead to genetic inconsistencies between the genotypes of parents and children; therefore, the analysis of STR mutation is more suited to assess the population mutation. In this study, we focused on 15 autosomal STR loci. DNA samples from a total of 42,416 unrelated healthy individuals (19,037 trios) from the population of Mainland China collected between Jan 2012 and May 2014 were successfully investigated. In our study, the allele frequencies, paternal mutation rates, maternal mutation rates and average mutation rates were detected. Furthermore, we also investigated the relationship between paternal ages, maternal ages, area, the time of pregnancy and average mutation rate. We found that the paternal mutation rate was higher than the maternal mutation rate and the paternal, maternal, and average mutation rates had a positive correlation with paternal age, maternal age and the time of pregnancy respectively. Additionally, the average mutation rate of coastal areas was higher than that of inland areas. PMID- 26273563 TI - Association analysis of polymorphism in thyroglobulin gene promoter with milk production traits in riverine buffalo (Bubalus bubalis). AB - Polymorphism within the promoter region of bovine thyroglobulin has been reported to be associated with milk and meat quality. In this study, we investigated the genetic variation within thyroglobulin promoter region of swamp and riverine buffaloes using PCR-SSCP technique and sequencing, and also analyzing association of polymorphism with the milk production traits. The study revealed four conformational patterns, A, B, C, and D among 323 buffaloes of two riverine breeds and different swamp populations. The frequency of SSCP variant 'A' was found to be invariably high among all buffalo populations. Variant 'C' was found to be absent in pure swamp population and present with higher frequency among riverine dairy breeds Mehsana and Nili Ravi. Frequency of D variant was observed to be highest in buffalo population, representing riverine and hybrid types. Sequencing of three representative PCR products of each of the SSCP variants, revealed three polymorphic sites responsible, 33C > T, 176G > T and 221C > T, in the buffalo TG promoter region. Further, association studies of SSCP variants with various milk production and milk quality traits indicated significant effect on fat percentage in buffaloes belonging to Mehsana and Nili Ravi dairy breeds. The preliminary results also showed the substantial variations in the distribution of SSCP variants' frequencies across swamp and riverine buffaloes, two distinct populations being reared for meat and milk production, respectively. PMID- 26273565 TI - The power and promise of applying genomics to honey bee health. AB - New genomic tools and resources are now being used to both understand honey bee health and develop tools to better manage it. Here, we describe the use of genomic approaches to identify and characterize bee parasites and pathogens, examine interactions among these parasites and pathogens, between them and their bee hosts, and to identify genetic markers for improved breeding of more resilient bee stocks. We also discuss several new genomic techniques that can be used to more efficiently study, monitor and improve bee health. In the case of using RNAi-based technologies to mitigate diseases in bee populations, we highlight advantages, disadvantages and strategies to reduce risk. The increased use of genomic analytical tools and manipulative technologies has already led to significant advances, and holds great promise for improvements in the health of honey bees and other critical pollinator species. PMID- 26273566 TI - Beneficial paracrine effects of adipocytes from obese rats on cultured endothelial cells. AB - The purpose was to test the hypothesis that adipocytes from obese rats would exert pro-atherogenic paracrine effects on cultured endothelial cells compared to adipocytes from lean rats, and that the adverse obesity-associated paracrine effects of adipocytes would be more pronounced in visceral than subcutaneous adipose tissue. Epididymal and subcutaneous adipose tissues were harvested from 32-wk old obese Otsuka Long Evans Tokushima Fatty (OLETF) and lean Long Evans Tokushima Otsuka (LETO) rats. Cultured rat aortic endothelial cells were treated for 24 hours with media conditioned with LETO subcutaneous adipocytes (LSA), OLETF subcutaneous adipocytes (OSA), LETO epididymal adipocytes (LEA), and OLETF epididymal adipocytes (OEA). The amounts of key adipokines secreted by ATs was measured in the supernatant fluid with ELISA and mRNA levels of a number of pro- and anti-atherogenic genes was assessed in treated endothelial cells via quantitative real-time PCR. Compared to adipocytes from other depots, secretion of leptin and TNFalpha was highest and vaspin secretion was lowest from OEA. However, endothelial cells treated with OEA conditioned media exhibited lower expression of several pro-atherogenic genes. These data suggest that adipocytes isolated from obese visceral adipose tissue secrete some as-yet unidentified factor(s) that confers a beneficial effect on transcription of pro- and anti atherogenic genes of endothelial cells. PMID- 26273564 TI - Antiviral Defense Mechanisms in Honey Bees. AB - Honey bees are significant pollinators of agricultural crops and other important plant species. High annual losses of honey bee colonies in North America and in some parts of Europe have profound ecological and economic implications. Colony losses have been attributed to multiple factors including RNA viruses, thus understanding bee antiviral defense mechanisms may result in the development of strategies that mitigate colony losses. Honey bee antiviral defense mechanisms include RNA-interference, pathogen-associated molecular pattern (PAMP) triggered signal transduction cascades, and reactive oxygen species generation. However, the relative importance of these and other pathways is largely uncharacterized. Herein we review the current understanding of honey bee antiviral defense mechanisms and suggest important avenues for future investigation. PMID- 26273567 TI - Online prevention of postpartum depression for Spanish- and English-speaking pregnant women: A pilot randomized controlled trial. AB - BACKGROUND: Postpartum depression (PPD) is a maternal mental health problem that affects women from all regions of the world. Unfortunately, even in developed countries, half of the cases go undetected and, consequently, untreated. Individuals from low and middle income countries trend toward underutilization of mental health services, partly due to the limited number of available psychological resources. The primary aims of this pilot randomized controlled trial were to adapt to the Internet the Mothers and Babies Course/Curso Mamas y Bebes, a prevention of PPD intervention, to describe the characteristics of the pregnant women who engaged in the intervention site, and to obtain preliminary data on the efficacy of the Internet intervention to reduce the risk of PPD. METHODS: Pregnant women, 18 years or older who were interested in using the site for themselves were recruited and randomly assigned to a fully-automated self help Internet intervention or to an information-only control condition. Randomized participants were invited to complete monthly depression assessments up to six months postpartum. To examine the prevention effects of the Internet intervention, pregnant women who did not meet current criteria for a major depressive episode, who engaged with the study website, and who provided depression data during the postpartum follow-up period were included in the study analyses. RESULTS: Participants were 111 predominantly Spanish-speaking (82.9%) and Latino/Hispanic (71.3%) pregnant women residing in 23 countries worldwide. The effect of the prevention intervention condition failed to reach significance at the a priori alpha-level. However, the observed coefficient trended in the hypothesized direction (b = -0.514, chi2 (1) = 3.43, p = .061; HR = 0.598). The benefits of receiving the e-MB Internet intervention was greater for pregnant women reporting high (vs. low) levels of prenatal depression symptoms (b = 0.605, chi2 (1) = 5.20, p =.023). CONCLUSIONS: This study provides preliminary evidence that Internet interventions are a promising method toward expanding the reach of psychological resources to perinatal women at-risk for PPD. PMID- 26273568 TI - INTERMITTENT DEGRADATION AND SCHIZOTYPY. AB - Intermittent degradation refers to transient detrimental disruptions in task performance. This phenomenon has been repeatedly observed in the performance data of patients with schizophrenia. Whether intermittent degradation is a feature of the liability for schizophrenia (i.e., schizotypy) is an open question. Further, the specificity of intermittent degradation to schizotypy has yet to be investigated. To address these questions, 92 undergraduate participants completed a battery of self-report questionnaires assessing schizotypy and psychological state variables (e.g., anxiety, depression), and their reaction times were recorded as they did so. Intermittent degradation was defined as the number of times a subject's reaction time for questionnaire items met or exceeded three standard deviations from his or her mean reaction time after controlling for each item's information processing load. Intermittent degradation scores were correlated with questionnaire scores. Our results indicate that intermittent degradation is associated with total scores on measures of positive and disorganized schizotypy, but unrelated to total scores on measures of negative schizotypy and psychological state variables. Intermittent degradation is interpreted as potentially derivative of schizotypy and a candidate endophenotypic marker worthy of continued research. PMID- 26273569 TI - Establishing Composite Cognitive Endpoints for Use in Preclinical Alzheimer's Disease Trials. PMID- 26273570 TI - Pneumococcal disease and use of pneumococcal vaccines in Taiwan. AB - The use of pneumococcal vaccine plays an important role for prevention of invasive pneumococcal disease (IPD). However, introducing the pneumococcal vaccine into the national immunization program (NIP) is complex and costly. The strategy of progressively integrating the pneumococcal conjugate vaccine (PCV) into the NIP in Taiwan provides valuable experience for policy makers. The 7 valent PCV (PCV7) was first available in Taiwan in late 2005. PCV7 was first provided free to children with underlying diseases, those in vulnerable socioeconomic status, and those with inadequate health care resources. The catch up immunization program with the 13-valent PCV was launched in 2013 and the national pneumococcal immunization program was implemented in 2015. Children aged 2-5 years had the highest incidence of IPD among pediatric population in Taiwan. Although the incidence of IPD caused by PCV7 serotypes has declined, the overall incidence of IPD remained high in the context of PCV7 use in the private sector. A surge of IPD caused by serotype 19A occurred, accounting for 53.6% of IPD cases among children aged <= 5 years in 2011-2012. After the implementation of the national pneumococcal immunization program, serogroup 15 has become the leading serogroup for IPD in children. Continued surveillance is necessary to monitor the serotype epidemiology in Taiwan. PMID- 26273571 TI - The present and future of veterinary vaccines for Japanese encephalitis in Korea. AB - Japanese encephalitis (JE) is a mosquito-borne zoonotic disease that affects approximately 50,000 people annually in Asia, causing 10,000 deaths. Considering the role of pigs as the virus-amplifying host and the economic loss in the swine industry, JE is an important disease for both public and animal health. A nationwide JE virus (JEV) vaccination program has been conducted annually for more than 30 years to prevent severe reproductive disorders in the Korean sow population. Remarkable progress in molecular biology has made it possible to analyze the genome of the vaccine strain at the nucleotide and amino acid levels. However, the scientific record of the current JEV veterinary vaccine has not been reported. Therefore, this article outlines the current JEV vaccine strain used in animals and discusses future directions for developing new veterinary JEV vaccines. PMID- 26273572 TI - Safety of influenza vaccination in children with allergic diseases. AB - Global guidelines strongly recommend annual influenza vaccination in people age 6 months and older, particularly in asthmatic children. There is no doubt about the benefit of influenza vaccination in asthmatic children. However, some of the vaccine's components may elicit an IgE mediated hypersensitivity or disease exacerbation, including life-threatening events, in children with allergic diseases. As a result, concerns regarding the safety of the vaccine still continue today. The influenza vaccine is grown on hens' eggs and contains a trace of egg protein. Consequently, it can provoke an allergic reaction or anaphylaxis in children with an egg allergy or exacerbation in those with asthma. Therefore, we need to know the risks and benefits of the influenza vaccine and the best strategy for safe vaccination. Although most guidelines have consistently reported the safety of influenza vaccination in children with allergic disease, and have recommended annual administration, safety concerns impede guideline based performance in practice. The safety and efficacy of influenza vaccination for allergic children are summarized in the present review. PMID- 26273574 TI - Porcine reproductive and respiratory syndrome virus vaccine does not fit in classical vaccinology. AB - All vaccines are developed to elicit an effective immune response in vaccinated animals such as innate, humoral and cell mediated response to protect animal health. Quality and intensity of the immune responses are differing by characteristics of the vaccine formulation and nature of the infectious agent. Modified live virus vaccines showed advantages over killed vaccines in terms of rapid immune response, duration of the immunity and better cell mediated protection mechanism. The porcine reproductive and respiratory syndrome virus (PRRSV) is relatively newly emerging (1986 in United States, 1990 in Europe) viral pathogen in pigs and tremendous effort has been made to protect pigs from this economically devastating disease such as developing killed, modified live, recombinant protein based and DNA vaccines. However, only cell culture attenuated virus vaccine is practiced with arguably limited efficacy. The PRRSV vaccine did not clear virus from infected pigs nor prevent re-infection of the virus. The vaccine showed very limited innate immune response, low anamnestic immune response and negligible cell mediated immune response. Despite of the current developed scientific technology, there still remain many questions to solve a most important pig disease worldwide. PMID- 26273573 TI - Application of radiation technology in vaccines development. AB - One of the earliest methods used in the manufacture of stable and safe vaccines is the use of chemical and physical treatments to produce inactivated forms of pathogens. Although these types of vaccines have been successful in eliciting specific humoral immune responses to pathogen-associated immunogens, there is a large demand for the development of fast, safe, and effective vaccine manufacturing strategies. Radiation sterilization has been used to develop a variety of vaccine types, because it can eradicate chemical contaminants and penetrate pathogens to destroy nucleic acids without damaging the pathogen surface antigens. Nevertheless, irradiated vaccines have not widely been used at an industrial level because of difficulties obtaining the necessary equipment. Recent successful clinical trials of irradiated vaccines against pathogens and tumors have led to a reevaluation of radiation technology as an alternative method to produce vaccines. In the present article, we review the challenges associated with creating irradiated vaccines and discuss potential strategies for developing vaccines using radiation technology. PMID- 26273575 TI - Porcine epidemic diarrhea: a review of current epidemiology and available vaccines. AB - Porcine epidemic diarrhea virus (PEDV), an Alphacoronavirus in the family Coronaviridae, causes acute diarrhea, vomiting, dehydration, and high mortality rates in neonatal piglets. PEDV can also cause diarrhea, agalactia, and abnormal reproductive cycles in pregnant sows. Although PEDV was first identified in Europe, it has resulted in significant economic losses in many Asian swine raising countries, including Korea, China, Japan, Vietnam, and the Philippines. However, from April 2013 to the present, major outbreaks of PEDV have been reported in the United States, Canada, and Mexico. Moreover, intercontinental transmission of PEDV has increased mortality rates in seronegative neonatal piglets, resulting in 10% loss of the US pig population. The emergence and re emergence of PEDV indicates that the virus is able to evade current vaccine strategies. Continuous emergence of multiple mutant strains from several regions has aggravated porcine epidemic diarrhea endemic conditions and highlighted the need for new vaccines based on the current circulating PEDV. Epidemic PEDV strains tend to be more pathogenic and cause increased death in pigs, thereby causing substantial financial losses for swine producers. In this review, we described the epidemiology of PEDV in several countries and present molecular characterization of current strains. We also discuss PEDV vaccines and related issues. PMID- 26273576 TI - Production of specific IgY Helicobacter pylori recombinant OipA protein and assessment of its inhibitory effects towards attachment of H. pylori to AGS cell line. AB - PURPOSE: The common triple therapy for Helicobacter pylori is challenged by the increasing cases of antibiotic resistant infections, raising the need to explore alternative therapies. Oral administration of egg yolk immunoglobulin Y (IgY) has been previously reported as a means of passive immunization therapy for H. pylori infections. In this work, we investigated the inhibitory effect of IgY on the attachment of H. pylori to AGS cell line. MATERIALS AND METHODS: Recombinant OipA was prepared. Hens were immunized with recombinant protein three times. IgY was purified from egg yolks of immunized hens using polyethylene glycol precipitation method. The inhibitory effect of the specific immunoglobulin was evaluated in AGS cell line infected with H. pylori. RESULTS: The presence of recombinant OipA (30 kD) was confirmed via sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Immunization of hens was confirmed using enzyme-linked immunosorbent assay. The purified IgY from egg yolks were assessed using SDS-PAGE and confirmed by western blot. CONCLUSION: The results showed that IgY-OipA had inhibitory effect on attachment of H. pylori to AGS cell line and may be utilized as a therapeutic or prophylaxis material. PMID- 26273577 TI - Immunity to tetanus in major beta thalassemia patients. AB - PURPOSE: Patients with beta thalassemia major are at increased risk for bacterial infections specially splenectomized patients. The aim of this study was to determine the anti-tetanus antibody concentration among patients with beta thalassemia major. MATERIALS AND METHODS: The anti-tetanus antibody concentration was investigated in 224 patients with thalassemia major and 224 healthy subjects matched for age and gender. Tetanus antibody and ferritin serum level were determined by enzyme-linked immunosorbent assay method using commercial kits. Subjects who had antibody level >= 0.1 IU/mL was defined as complete protection, 0.01 to < 0.1 IU/mL as partial protection and < 0.01 IU/mL as no protection. For the analysis, we used SPSS version 11.5 software. A two-sided p-value less 0.05 was considered statistically significant. RESULTS: In patients with beta thalassemia major, antibody level against tetanus was inversely dependent about 29.3% to serum ferritin level. Thus, when serum ferritin increased 1 ng/mL, serum antibody against tetanus decreased 0.002 IU/mL. Mean anti-tetanus (IgG) antibody titers was lower in thalassemia patients compared to healthy subjects (1.53 +/- 1.71 vs. 2.02 +/- 2.05, p = 0.007) that was no significantly associated to age and gender in both study groups. All of participants had serum antibody level 0.01 IU/mL or greater. The complete protective level of anti-tetanus antibody was lower in thalassemia subjects in compare to healthy persons (71% vs. 87.9%, p < 0.001). CONCLUSION: Patients with thalassemia had lower anti-tetanus antibody level than healthy subjects. Thus the vaccine recommendation seems essential for patients with beta thalassemia major. PMID- 26273578 TI - Application of recombinant adenoviruses expressing glycoprotein or nucleoprotein of rabies virus to Korean raccoon dogs. AB - PURPOSE: A new rabies vaccine for animals, including raccoon dogs, in Korea is needed to eradicate rabies infection. In this study, we constructed two recombinant adenoviruses expressing the glycoprotein or nucleoprotein of the rabies virus (RABV). We then investigated the safety and immunogenicity of these strains in raccoon dogs, depending on inoculation route. MATERIALS AND METHODS: Recombinant adenoviruses expressing the glycoprotein (Ad-0910G) or nucleoprotein (Ad-0910N) of rabies were constructed in 293A cells using an adenoviral system. One-year-old raccoon dogs underwent intramuscular (IM) inoculation or oral administration of the recombinant Ad-0910G and Ad-0910N. Clinical symptoms were observed and virus-neutralizing antibodies (VNA) against RABV were measured at 0, 2, 4, and 6 weeks after the immunization. Raccoons were considered positive if VNA titers were >= 0.1 IU/mL. RESULTS: Raccoon dogs inoculated with the combined Ad-0910G and Ad-0910N virus via the IM route did not exhibit any clinical sign of rabies during the observation period. All raccoon dogs (n = 7) immunized IM had high VNA titers, ranging from 0.17 to 41.6 IU/mL at 2 weeks after inoculation, but 70% (7/10) of raccoon dogs administered viruses via the oral route responded by 6 weeks after administration against RABV. CONCLUSION: Raccoon dogs inoculated with Ad-0910G and Ad-0910N viruses showed no adverse effects. Immunization with the combined Ad-0910G and Ad-0910N strains may play an important role in inducing VNA against RABV in raccoon dogs. PMID- 26273579 TI - Adverse reactions to Mycobacterium bovis bacille Calmette-Guerin vaccination against tuberculosis in Iranian children. AB - PURPOSE: There are considerable variations in the number of adverse reaction reports related to vaccine from different countries. The aim of this study was to review the development of adverse reactions to bacille Calmette-Guerin (BCG) vaccination among hospitalized patients in an Iranian referral hospital. MATERIALS AND METHODS: We identified hospitalized patients with BCG complications in Pediatric Infectious Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran during January 2007-April 2009. Data on demographics, clinical features, laboratory findings, personal history (including vaccination history), family history, and outcomes were retrieved from medical records. RESULTS: There were 46 cases with BCG complication during the 2 years period. All of the children received vaccination at birth. Twenty-eight patients (61%) were male. The mean age of the patients was 13.5 +/-11.3 months (range, 1 to 52 months; median, 10 months). The majority of children (57%) with BCG complication were less than 1 year old. Among hospitalized patients due to BCG complications, suppurative lymphadenitis was occurred in 28 children (61%) and lymphadenopathy was seen in 9 children (20%). Disseminated BCG was detected in 8 patients (17%) and only 1 child (2%) was presented with abscess. In 7% (n = 3) of children, the family history of BCG complications were positive. CONCLUSION: The most common side effect of the BCG vaccine in our study was suppurative lymphadenitis. Disseminated BCG infection in complications leading to hospitalization in our study was 17%. With regard to the difficulty in implementing such a guideline in settings where BCG is given to all newborns, registration of Iranian primary immunodeficiency disorders (PID) patients would be helpful to increase the awareness of medical community of Iran to investigate underlying disease. In addition, BCG vaccination should postpone in each newborn with a family history of PID until the definite condition has been ruled out. PMID- 26273580 TI - Suggested guidelines for vaccination of cattle in Korea. AB - There is no published vaccination guideline to cattle even though each vaccine company suggested the program based on their products. Also, most of veterinary vaccines are multivalent. Therefore, it is very difficult to standardize the program. Now, we are suggesting the general vaccine programs based current situations in cattle industry in Korea. PMID- 26273581 TI - Nonlocal Electrostatics in Spherical Geometries Using Eigenfunction Expansions of Boundary-Integral Operators. AB - In this paper, we present an exact, infinite-series solution to Lorentz nonlocal continuum electrostatics for an arbitrary charge distribution in a spherical solute. Our approach relies on two key steps: (1) re-formulating the PDE problem using boundary-integral equations, and (2) diagonalizing the boundary-integral operators using the fact that their eigenfunctions are the surface spherical harmonics. To introduce this uncommon approach for calculations in separable geometries, we first re-derive Kirkwood's classic results for a protein surrounded concentrically by a pure-water ion-exclusion (Stern) layer and then a dilute electrolyte, which is modeled with the linearized Poisson-Boltzmann equation. The eigenfunction-expansion approach provides a computationally efficient way to test some implications of nonlocal models, including estimating the reasonable range of the nonlocal length-scale parameter lambda. Our results suggest that nonlocal solvent response may help to reduce the need for very high dielectric constants in calculating pH-dependent protein behavior, though more sophisticated nonlocal models are needed to resolve this question in full. An open-source MATLAB implementation of our approach is freely available online. PMID- 26273582 TI - Comment on "Some Aspects of Nonbeverage Alcohol Consumption in the Former Soviet Union". PMID- 26273583 TI - Does Diacylglycerol Accumulation in Fatty Liver Disease Cause Hepatic Insulin Resistance? AB - Numerous studies conducted on obese humans and various rodent models of obesity have identified a correlation between hepatic lipid content and the development of insulin resistance in liver and other tissues. Despite a large body of the literature on this topic, the cause and effect relationship between hepatic steatosis and insulin resistance remains controversial. If, as many believe, lipid aggregation in liver drives insulin resistance and other metabolic abnormalities, there are significant unanswered questions as to which lipid mediators are causative in this cascade. Several published papers have now correlated levels of diacylglycerol (DAG), the penultimate intermediate in triglyceride synthesis, with development of insulin resistance and have postulated that this occurs via activation of protein kinase C signaling. Although many studies have confirmed this relationship, many others have reported a disconnect between DAG content and insulin resistance. It has been postulated that differences in methods for DAG measurement, DAG compartmentalization within the cell, or fatty acid composition of the DAG may explain these discrepancies. The purpose of this review is to compare and contrast some of the relevant findings in this area and to discuss a number of unanswered questions regarding the relationship between DAG and insulin resistance. PMID- 26273584 TI - Differences in Velopharyngeal Structure during Speech among Asians Revealed by 3 Tesla Magnetic Resonance Imaging Movie Mode. AB - OBJECTIVE: Different bony structures can affect the function of the velopharyngeal muscles. Asian populations differ morphologically, including the morphologies of their bony structures. The purpose of this study was to compare the velopharyngeal structures during speech in two Asian populations: Japanese and Thai. METHODS: Ten healthy Japanese and Thai females (five each) were evaluated with a 3-Tesla (3 T) magnetic resonance imaging (MRI) scanner while they produced vowel-consonant-vowel syllable (/asa/). A gradient-echo sequence, fast low-angle shot with segmented cine and parallel imaging technique was used to obtain sagittal images of the velopharyngeal structures. RESULTS: MRI was carried out in real time during speech production, allowing investigations of the time-to-time changes in the velopharyngeal structures. Thai subjects had a significantly longer hard palate and produced shorter consonant than Japanese subjects. The velum of the Thai participants showed significant thickening during consonant production and their retroglossal space was significantly wider at rest, whereas the dimensional change during task performance was similar in the two populations. CONCLUSIONS: The 3 T MRI movie method can be used to investigate velopharyngeal function and diagnose velopharyngeal insufficiency. The racial differences may include differences in skeletal patterns and soft-tissue morphology that result in functional differences for the affected structures. PMID- 26273585 TI - Tobacco Usage in Uttarakhand: A Dangerous Combination of High Prevalence, Widespread Ignorance, and Resistance to Quitting. AB - BACKGROUND: Nearly one-third of adults in India use tobacco, resulting in 1.2 million deaths. However, little is known about knowledge, attitudes, and practices (KAP) related to smoking in the impoverished state of Uttarakhand. METHODS: A cross-sectional epidemiological prevalence survey was undertaken. Multistage cluster sampling selected 20 villages and 50 households to survey from which 1853 people were interviewed. Tobacco prevalence and KAP were analyzed by income level, occupation, age, and sex. 95% confidence intervals were calculated using standard formulas and incorporating assumptions in relation to the clustering effect. RESULTS: The overall prevalence of tobacco usage, defined using WHO criteria, was 38.9%. 93% of smokers and 86% of tobacco chewers were male. Prevalence of tobacco use, controlling for other factors, was associated with lower education, older age, and male sex. 97.6% of users and 98.1% of nonusers wanted less tobacco. Except for lung cancer (89% awareness), awareness of diseases caused by tobacco usage was low (cardiac: 67%; infertility: 32.5%; stroke: 40.5%). CONCLUSION: A dangerous combination of high tobacco usage prevalence, ignorance about its dangers, and few quit attempts being made suggests the need to develop effective and evidence based interventions to prevent a health and development disaster in Uttarakhand. PMID- 26273586 TI - The Current and Future Use of Ridge Regression for Prediction in Quantitative Genetics. AB - In recent years, there has been a considerable amount of research on the use of regularization methods for inference and prediction in quantitative genetics. Such research mostly focuses on selection of markers and shrinkage of their effects. In this review paper, the use of ridge regression for prediction in quantitative genetics using single-nucleotide polymorphism data is discussed. In particular, we consider (i) the theoretical foundations of ridge regression, (ii) its link to commonly used methods in animal breeding, (iii) the computational feasibility, and (iv) the scope for constructing prediction models with nonlinear effects (e.g., dominance and epistasis). Based on a simulation study we gauge the current and future potential of ridge regression for prediction of human traits using genome-wide SNP data. We conclude that, for outcomes with a relatively simple genetic architecture, given current sample sizes in most cohorts (i.e., N < 10,000) the predictive accuracy of ridge regression is slightly higher than the classical genome-wide association study approach of repeated simple regression (i.e., one regression per SNP). However, both capture only a small proportion of the heritability. Nevertheless, we find evidence that for large-scale initiatives, such as biobanks, sample sizes can be achieved where ridge regression compared to the classical approach improves predictive accuracy substantially. PMID- 26273587 TI - An Association Rule Mining Approach to Discover lncRNAs Expression Patterns in Cancer Datasets. AB - In the past few years, the role of long noncoding RNAs (lncRNAs) in tumor development and progression has been disclosed although their mechanisms of action remain to be elucidated. An important contribution to the comprehension of lncRNAs biology in cancer could be obtained through the integrated analysis of multiple expression datasets. However, the growing availability of public datasets requires new data mining techniques to integrate and describe relationship among data. In this perspective, we explored the powerness of the Association Rule Mining (ARM) approach in gene expression data analysis. By the ARM method, we performed a meta-analysis of cancer-related microarray data which allowed us to identify and characterize a set of ten lncRNAs simultaneously altered in different brain tumor datasets. The expression profiles of the ten lncRNAs appeared to be sufficient to distinguish between cancer and normal tissues. A further characterization of this lncRNAs signature through a comodulation expression analysis suggested that biological processes specific of the nervous system could be compromised. PMID- 26273589 TI - Histological and Histomorphometric Human Results of HA-Beta-TCP 30/70 Compared to Three Different Biomaterials in Maxillary Sinus Augmentation at 6 Months: A Preliminary Report. AB - OBJECTIVE: The aim of this investigation was to examine the bone regenerative potential of newly biphasic calcium phosphate ceramics (HA-beta-TCP 30/70), by assessing histological and histomorphometric results of human specimens retrieved from sinuses augmented with HA-beta-TCP 30/70, and comparing them to anorganic bovine bone (ABB), mineralized solvent-dehydrated bone allograft (MSDBA), and equine bone (EB), after a healing period of 6 months. MATERIALS AND METHODS: Four consecutive patients with edentulous atrophic posterior maxilla were included in this report. A two-stage procedure was carried out for sinus augmentation with HA beta-TCP 30/70, ABB, MSDBA, and EB. After 6 months, specimens were retrieved at the time of implant placement and processed for histological and histomorphometric analyses. RESULTS: At histological examination, all biomaterials were in close contact with the newly formed bone and showed the same pattern of bone formation; the grafted granules were surrounded by a bridge-like network of newly formed bone. A limited number of ABB particles were partially covered by connective tissue. The histomorphometric analysis revealed 30.2% newly formed bone for Ha-beta-TCP 30/70, 20.1% for ABB, 16.4% for MSDBA, and 21.9% for EB. CONCLUSIONS: Within the limitations of the present investigation, these results support the successful use of HA-beta-TCP 30/70 for sinus augmentation. PMID- 26273588 TI - Splicing Regulators and Their Roles in Cancer Biology and Therapy. AB - Alternative splicing allows cells to expand the encoding potential of their genomes. In this elegant mechanism, a single gene can yield protein isoforms with even antagonistic functions depending on the cellular physiological context. Alterations in splicing regulatory factors activity in cancer cells, however, can generate an abnormal protein expression pattern that promotes growth, survival, and other processes, which are relevant to tumor biology. In this review, we discuss dysregulated alternative splicing events and regulatory factors that impact pathways related to cancer. The SR proteins and their regulatory kinases SRPKs and CLKs have been frequently found altered in tumors and are examined in more detail. Finally, perspectives that support splicing machinery as target for the development of novel anticancer therapies are discussed. PMID- 26273590 TI - Oral Streptococci Biofilm Formation on Different Implant Surface Topographies. AB - The establishment of the subgingival microbiota is dependent on successive colonization of the implant surface by bacterial species. Different implant surface topographies could influence the bacterial adsorption and therefore jeopardize the implant survival. This study evaluated the biofilm formation capacity of five oral streptococci species on two titanium surface topographies. In vitro biofilm formation was induced on 30 titanium discs divided in two groups: sandblasted acid-etched (SAE- n = 15) and as-machined (M- n = 15) surface. The specimens were immersed in sterilized whole human unstimulated saliva and then in fresh bacterial culture with five oral streptococci species: Streptococcus sanguinis, Streptococcus salivarius, Streptococcus mutans, Streptococcus sobrinus, and Streptococcus cricetus. The specimens were fixed and stained and the adsorbed dye was measured. Surface characterization was performed by atomic force and scanning electron microscopy. Surface and microbiologic data were analyzed by Student's t-test and two-way ANOVA, respectively (P < 0.05). S. cricetus, S. mutans, and S. sobrinus exhibited higher biofilm formation and no differences were observed between surfaces analyzed within each species (P > 0.05). S. sanguinis exhibited similar behavior to form biofilm on both implant surface topographies, while S. salivarius showed the lowest ability to form biofilm. It was concluded that biofilm formation on titanium surfaces depends on surface topography and species involved. PMID- 26273592 TI - Isolation and Characterization of Phages Infecting Bacillus subtilis. AB - Bacteriophages have been suggested as an alternative approach to reduce the amount of pathogens in various applications. Bacteriophages of various specificity and virulence were isolated as a means of controlling food-borne pathogens. We studied the interaction of bacteriophages with Bacillus species, which are very often persistent in industrial applications such as food production due to their antibiotic resistance and spore formation. A comparative study using electron microscopy, PFGE, and SDS-PAGE as well as determination of host range, pH and temperature resistance, adsorption rate, latent time, and phage burst size was performed on three phages of the Myoviridae family and one phage of the Siphoviridae family which infected Bacillus subtilis strains. The phages are morphologically different and characterized by icosahedral heads and contractile (SIOPhi, SUBomega, and SPOsigma phages) or noncontractile (ARpi phage) tails. The genomes of SIOPhi and SUBomega are composed of 154 kb. The capsid of SIOPhi is composed of four proteins. Bacteriophages SPOsigma and ARpi have genome sizes of 25 kbp and 40 kbp, respectively. Both phages as well as SUBomega phage have 14 proteins in their capsids. Phages SIOPhi and SPOsigma are resistant to high temperatures and to the acid (4.0) and alkaline (9.0 and 10.0) pH. PMID- 26273591 TI - Drug Induced Steatohepatitis: An Uncommon Culprit of a Common Disease. AB - Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease in developed countries. Its frequency is increasing in the general population mostly due to the widespread occurrence of obesity and the metabolic syndrome. Although drugs and dietary supplements are viewed as a major cause of acute liver injury, drug induced steatosis and steatohepatitis are considered a rare form of drug induced liver injury (DILI). The complex mechanism leading to hepatic steatosis caused by commonly used drugs such as amiodarone, methotrexate, tamoxifen, valproic acid, glucocorticoids, and others is not fully understood. It relates not only to induction of the metabolic syndrome by some drugs but also to their impact on important molecular pathways including increased hepatocytes lipogenesis, decreased secretion of fatty acids, and interruption of mitochondrial beta-oxidation as well as altered expression of genes responsible for drug metabolism. Better familiarity with this type of liver injury is important for early recognition of drug hepatotoxicity and crucial for preventing severe forms of liver injury and cirrhosis. Moreover, understanding the mechanisms leading to drug induced hepatic steatosis may provide much needed clues to the mechanism and potential prevention of the more common form of metabolic steatohepatitis. PMID- 26273593 TI - Clinical Outcomes of Primary Palatal Surgery in Children with Nonsyndromic Cleft Palate with and without Lip. AB - This study presents clinical outcomes of primary cleft palate surgery, including rate of oronasal fistula development, rate of velopharyngeal insufficiency (VPI) requiring secondary surgery, and speech outcomes. We examined the effect of cleft type on the clinical outcomes. Retrospective analysis was performed using clinical records of all patients who received a primary palatoplasty at the Cleft Palate Clinic at Seoul Asan Medical Center, South Korea, between 2007 and 2012. The study included 292 patients with nonsyndromic overt cleft palate (+/- cleft lip). The results revealed that the rate of oronasal fistula was 7.9% and the incidence of VPI based on the rate of secondary palatal surgery was 19.2%. The results showed that 50.3% of all the patients had received speech therapy and 28.8% and 51.4% demonstrated significant hypernasality and articulatory deficits, respectively. The results of the rate of VPI and speech outcomes were significantly different in terms of cleft type. Except for the rate of oronasal fistula, patients with cleft palate generally exhibited better clinical outcomes compared to those with bilateral or unilateral cleft lip and palate. This study suggests that several factors, including cleft type, should be identified and comprehensively considered to establish an optimal treatment regimen for patients with cleft palate. PMID- 26273594 TI - Bacterial Diversity Associated with the Coccolithophorid Algae Emiliania huxleyi and Coccolithus pelagicus f. braarudii. AB - Coccolithophores are unicellular calcifying marine phytoplankton that can form large and conspicuous blooms in the oceans and make significant contributions to oceanic carbon cycling and atmospheric CO2 regulation. Despite their importance, the bacterial diversity associated with these algae has not been explored for ecological or biotechnological reasons. Bacterial membership of Emiliania huxleyi and Coccolithus pelagicus f. braarudii cultures was assessed using cultivation and cultivation-independent methods. The communities were species rich compared to other phytoplankton cultures. Community analysis identified specific taxa which cooccur in all cultures (Marinobacter and Marivita). Hydrocarbon-degrading bacteria were found in all cultures. The presence of Acidobacteria, Acidimicrobidae, Schlegelella, and Thermomonas was unprecedented but were potentially explained by calcification associated with coccolith production. One strain of Acidobacteria was cultivated and is closely related to a marine Acidobacteria isolated from a sponge. From this assessment of the bacterial diversity of coccolithophores, a number of biotechnological opportunities are evident, from bioprospecting for novel taxa such as Acidobacteria to helping understand the relationship between obligate hydrocarbonoclastic bacteria occurrence with phytoplankton and to revealing bacterial taxa that have a specific association with algae and may be suitable candidates as a means to improve the efficiency of mass algal cultivation. PMID- 26273596 TI - Network Comparison of Inflammation in Colorectal Cancer and Alzheimer's Disease. AB - Recently, a large clinical study revealed an inverse correlation of individual risk of cancer versus Alzheimer's disease (AD). However, no explanation exists for this anticorrelation at the molecular level; however, inflammation is crucial to the pathogenesis of both diseases, necessitating a need to understand differing signaling usage during inflammatory responses distinct to both diseases. Using a subpathway analysis approach, we identified numerous well-known and previously unknown pathways enriched in datasets from both diseases. Here, we present the quantitative importance of the inflammatory response in the two disease pathologies and summarize signal transduction pathways common to both diseases that are affected by inflammation. PMID- 26273595 TI - Current Controversies in Diagnosis and Management of Cleft Palate and Velopharyngeal Insufficiency. AB - BACKGROUND: One of the most controversial topics concerning cleft palate is the diagnosis and treatment of velopharyngeal insufficiency (VPI). OBJECTIVE: This paper reviews current genetic aspects of cleft palate, imaging diagnosis of VPI, the planning of operations for restoring velopharyngeal function during speech, and strategies for speech pathology treatment of articulation disorders in patients with cleft palate. MATERIALS AND METHODS: An updated review of the scientific literature concerning genetic aspects of cleft palate was carried out. Current strategies for assessing and treating articulation disorders associated with cleft palate were analyzed. Imaging procedures for assessing velopharyngeal closure during speech were reviewed, including a recent method for performing intraoperative videonasopharyngoscopy. RESULTS: Conclusions from the analysis of genetic aspects of syndromic and nonsyndromic cleft palate and their use in its diagnosis and management are presented. Strategies for classifying and treating articulation disorders in patients with cleft palate are presented. Preliminary results of the use of multiplanar videofluoroscopy as an outpatient procedure and intraoperative endoscopy for the planning of operations which aimed to correct VPI are presented. CONCLUSION: This paper presents current aspects of the diagnosis and management of patients with cleft palate and VPI including 3 main aspects: genetics and genomics, speech pathology and imaging diagnosis, and surgical management. PMID- 26273597 TI - New Biomaterials and Regenerative Medicine Strategies in Periodontology, Oral Surgery, Esthetic and Implant Dentistry. PMID- 26273598 TI - Association of Nonalcoholic Fatty Liver Disease with Subclinical Cardiovascular Changes: A Systematic Review and Meta-Analysis. AB - In the last 20 years, nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide, primarily as a result of the epidemic of obesity. NAFLD is strongly associated with insulin resistance, glucose intolerance, and dyslipidemia and is currently regarded as the liver manifestation of the metabolic syndrome, a highly atherogenic condition even at a very early age. Patients with NAFLD including pediatric subjects have a higher prevalence of subclinical atherosclerosis, as shown by impaired flow-mediated vasodilation, increased carotid artery intima-media thickness, and arterial stiffness, which are independent of obesity and other established risk factors. More recent work has identified NAFLD as a risk factor not only for premature coronary heart disease and cardiovascular events, but also for early subclinical abnormalities in myocardial structure and function. Thus, we conducted a systematic review and meta-analysis to test the hypothesis that NAFLD is associated with evidence of subclinical cardiac structural and functional abnormalities. PMID- 26273599 TI - Inhibitory Effect of a Novel Antirheumatic Drug T-614 on the IL-6-Induced RANKL/OPG, IL-17, and MMP-3 Expression in Synovial Fibroblasts from Rheumatoid Arthritis Patients. AB - T-614 (also named as iguratimod), a novel antirheumatic drug, could attenuate joint inflammation and articular damage in rheumatoid arthritis (RA) patients, providing a new therapy for RA. Here, we tested the role T-614 on the IL-6 induced receptor activator of nuclear factor kappaB ligand (RANKL)/osteoprotegerin (OPG), IL-17, and MMP-3 expression in synovial fibroblasts from rheumatoid arthritis (RASFs) patients. T-614 decreased RANKL expression and RANKL/OPG ratio in IL-6-induced RASFs. We confirmed this effect by a decrease of the mRNA and protein RANKL and mRNA RANKL/OPG in RASFs exposed in vitro to T-614 or MTX. Markedly decreased levels of IL-17, retinoid-related orphan receptor C (RORc), and MMP-3 mRNA expression were also observed in IL-6 induced RASFs in the presence of T-614 or MTX compared with those in its absence. Furthermore, T-614 blocked expression of p-ERK1/2 protein without affecting ERK1/2 expression, indicating that the way that T-614 regulated RANKL expression might be ERK1/2 pathway. Our results suggest that T-614 yields a strong improvement in arthritis via exact suppression of RANKL/OPG, IL-17, and MMP-3 expression in RASFs. PMID- 26273600 TI - Diverse Reductive Dehalogenases Are Associated with Clostridiales-Enriched Microcosms Dechlorinating 1,2-Dichloroethane. AB - The achievement of successful biostimulation of active microbiomes for the cleanup of a polluted site is strictly dependent on the knowledge of the key microorganisms equipped with the relevant catabolic genes responsible for the degradation process. In this work, we present the characterization of the bacterial community developed in anaerobic microcosms after biostimulation with the electron donor lactate of groundwater polluted with 1,2-dichloroethane (1,2 DCA). Through a multilevel analysis, we have assessed (i) the structural analysis of the bacterial community; (ii) the identification of putative dehalorespiring bacteria; (iii) the characterization of functional genes encoding for putative 1,2-DCA reductive dehalogenases (RDs). Following the biostimulation treatment, the structure of the bacterial community underwent a notable change of the main phylotypes, with the enrichment of representatives of the order Clostridiales. Through PCR targeting conserved regions within known RD genes, four novel variants of RDs previously associated with the reductive dechlorination of 1,2 DCA were identified in the metagenome of the Clostridiales-dominated bacterial community. PMID- 26273601 TI - The Anthropometric Measurement of Schober's Test in Normal Taiwanese Population. AB - The measurement of lower back mobility is essential in the assessment of lower back pain including ankylosing spondylitis. Original Schober's test (OST) and modified Schober's test (MST) are popularly conducted in daily rheumatology and orthopedics clinical practices. To our knowledge, this report is the only anthropometric reference study in a normal oriental population. The OST declined with age from 5.0 cm in the youngest (20-30 years old) to 3.1 cm in the aged (70 80 years old) male subjects and from 3.6 cm to 2.4 cm in the female subjects. The male OST was significantly more than the female OST. There was a good correlation between OST and MST in each of the three age groups of both sexes. PMID- 26273602 TI - Smoking Cessation and Socioeconomic Status: An Update of Existing Evidence from a National Evaluation of English Stop Smoking Services. AB - Smokers from lower socioeconomic groups are less likely to be successful in stopping smoking than more affluent smokers, even after accessing cessation programmes. Data were analysed from 3057 clients of nine services. Routine monitoring data were expanded with CO validated smoking status at 52-week follow up. Backwards logistic regression modelling was used to consider which factors were most important in explaining the relationship between SES and quitting. The odds ratio of stopping smoking among more affluent clients, compared with more disadvantaged clients, after taking into account design variables only, was 1.85 (95% CI 1.44 to 2.37) which declined to 1.44 (1.11 to 1.87) when all controls were included. The factors that explained more than 10% of the decline in the odds ratio were age, proportion of friends and family who smoked, nicotine dependence, and taking varenicline. A range of factors contribute to lower cessation rates for disadvantaged smokers. Some of these can be modified by improved smoking cessation service provision, but others require contributions from wider efforts to improve material, human, and social capital. PMID- 26273603 TI - Posttranscriptional Regulation of Splicing Factor SRSF1 and Its Role in Cancer Cell Biology. AB - Over the past decade, alternative splicing has been progressively recognized as a major mechanism regulating gene expression patterns in different tissues and disease states through the generation of multiple mRNAs from the same gene transcript. This process requires the joining of selected exons or usage of different pairs of splice sites and is regulated by gene-specific combinations of RNA-binding proteins. One archetypical splicing regulator is SRSF1, for which we review the molecular mechanisms and posttranscriptional modifications involved in its life cycle. These include alternative splicing of SRSF1 itself, regulatory protein phosphorylation events, and the role of nuclear versus cytoplasmic SRSF1 localization. In addition, we resume current knowledge on deregulated SRSF1 expression in tumors and describe SRSF1-regulated alternative transcripts with functional consequences for cancer cell biology at different stages of tumor development. PMID- 26273604 TI - The Potential Role of Iron and Copper in Pediatric Obesity and Nonalcoholic Fatty Liver Disease. AB - Obesity is a rapidly growing health problem and is paralleled by a multitude of comorbidities, including nonalcoholic fatty liver disease (NAFLD). NAFLD has become the most common chronic liver disease in both adults and children. The current understanding of NAFLD is still fragmentary. While simple steatosis is characterized by the interplay between excessive free fatty acid accumulation and hepatic insulin resistance, the progression to NASH has been related to oxidative stress and a proinflammatory state with dysbalanced adipokine, cytokine levels, and endotoxin-mediated immune response. In addition, oxidative stress has been suggested to play a central role for the sequelae leading to NASH. Trace elements are critical in regulatory, immunologic, and antioxidant functions resulting in protection against inflammation and peroxidation and consequently against the known comorbidities of obesity. Disruptions of the metal detoxification processes located in the liver are plausibly related to NAFLD development via oxidative stress. Perturbations of iron and copper (Cu) homeostasis have been shown to contribute to the pathogenesis of NAFLD. This review presents current data from pediatric studies. In addition, data from adult studies are summarized where clinical relevance may be extrapolated to pediatric obesity and NAFLD. PMID- 26273605 TI - Expression of Heterologous Cellulases in Thermotoga sp. Strain RQ2. AB - The ability of Thermotoga spp. to degrade cellulose is limited due to a lack of exoglucanases. To address this deficiency, cellulase genes Csac_1076 (celA) and Csac_1078 (celB) from Caldicellulosiruptor saccharolyticus were cloned into T. sp. strain RQ2 for heterologous overexpression. Coding regions of Csac_1076 and Csac_1078 were fused to the signal peptide of TM1840 (amyA) and TM0070 (xynB), resulting in three chimeric enzymes, namely, TM1840-Csac_1078, TM0070-Csac_1078, and TM0070-Csac_1076, which were carried by Thermotoga-E. coli shuttle vectors pHX02, pHX04, and pHX07, respectively. All three recombinant enzymes were successfully expressed in E. coli DH5alpha and T. sp. strain RQ2, rendering the hosts with increased endo- and/or exoglucanase activities. In E. coli, the recombinant enzymes were mainly bound to the bacterial cells, whereas in T. sp. strain RQ2, about half of the enzyme activities were observed in the culture supernatants. However, the cellulase activities were lost in T. sp. strain RQ2 after three consecutive transfers. Nevertheless, this is the first time heterologous genes bigger than 1 kb (up to 5.3 kb in this study) have ever been expressed in Thermotoga, demonstrating the feasibility of using engineered Thermotoga spp. for efficient cellulose utilization. PMID- 26273606 TI - The Epidemiology of Tobacco Use among Khat Users: A Systematic Review. AB - Khat, an "amphetamine-like green leaf," may influence the consumption of tobacco. This study reviews the epidemiology of tobacco use among khat users. Electronic database searches using appropriate keywords/terms were conducted to identify observational studies of khat use. Assessment of quality and risk of bias of all included studies was conducted, and the results were synthesised descriptively. Nine eligible cross-sectional studies were identified. All assessed self-reported tobacco among khat users and were carried out in Africa and the Middle East. Eight reported cigarettes and one reported waterpipes as the mode of use. Methods of tobacco use prevalence assessment varied. Prevalence of "current" tobacco use among students and university teachers ranged from 29 to 37%; "lifetime" tobacco use in university teachers was 58% and "undefined" tobacco use in nonspecific adults and students ranged from 17 to 78%. Daily tobacco use among adults was reported as 17% whilst simultaneous tobacco and khat use was reported as between 14 and 30% in students. In conclusion, tobacco prevalence among khat users appears significant. Findings should be interpreted cautiously due to self reported tobacco use, diversity in questions assessing tobacco use, and type of tobacco consumption. Future research should address the methodological shortcomings identified in this review before appropriate policy interventions can be developed. PMID- 26273607 TI - Gene Coexpression and Evolutionary Conservation Analysis of the Human Preimplantation Embryos. AB - Evolutionary developmental biology (EVO-DEVO) tries to decode evolutionary constraints on the stages of embryonic development. Two models--the "funnel-like" model and the "hourglass" model--have been proposed by investigators to illustrate the fluctuation of selective pressure on these stages. However, selective indices of stages corresponding to mammalian preimplantation embryonic development (PED) were undetected in previous studies. Based on single cell RNA sequencing of stages during human PED, we used coexpression method to identify gene modules activated in each of these stages. Through measuring the evolutionary indices of gene modules belonging to each stage, we observed change pattern of selective constraints on PED for the first time. The selective pressure decreases from the zygote stage to the 4-cell stage and increases at the 8-cell stage and then decreases again from 8-cell stage to the late blastocyst stages. Previous EVO-DEVO studies concerning the whole embryo development neglected the fluctuation of selective pressure in these earlier stages, and the fluctuation was potentially correlated with events of earlier stages, such as zygote genome activation (ZGA). Such oscillation in an earlier stage would further affect models of the evolutionary constraints on whole embryo development. Therefore, these earlier stages should be measured intensively in future EVO-DEVO studies. PMID- 26273608 TI - FARMS: A New Algorithm for Variable Selection. AB - Large datasets including an extensive number of covariates are generated these days in many different situations, for instance, in detailed genetic studies of outbreed human populations or in complex analyses of immune responses to different infections. Aiming at informing clinical interventions or vaccine design, methods for variable selection identifying those variables with the optimal prediction performance for a specific outcome are crucial. However, testing for all potential subsets of variables is not feasible and alternatives to existing methods are needed. Here, we describe a new method to handle such complex datasets, referred to as FARMS, that combines forward and all subsets regression for model selection. We apply FARMS to a host genetic and immunological dataset of over 800 individuals from Lima (Peru) and Durban (South Africa) who were HIV infected and tested for antiviral immune responses. This dataset includes more than 500 explanatory variables: around 400 variables with information on HIV immune reactivity and around 100 individual genetic characteristics. We have implemented FARMS in R statistical language and we showed that FARMS is fast and outcompetes other comparable commonly used approaches, thus providing a new tool for the thorough analysis of complex datasets without the need for massive computational infrastructure. PMID- 26273609 TI - Development of Electroactive and Anaerobic Ammonium-Oxidizing (Anammox) Biofilms from Digestate in Microbial Fuel Cells. AB - Microbial Fuel cells (MFCs) have been proposed for nutrient removal and energy recovery from different wastes. In this study the anaerobic digestate was used to feed H-type MFC reactors, one with a graphite anode preconditioned with Geobacter sulfurreducens and the other with an unconditioned graphite anode. The data demonstrate that the digestate acts as a carbon source, and even in the absence of anode preconditioning, electroactive bacteria colonise the anodic chamber, producing a maximum power density of 172.2 mW/m(2). The carbon content was also reduced by up to 60%, while anaerobic ammonium oxidation (anammox) bacteria, which were found in the anodic compartment of the reactors, contributed to nitrogen removal from the digestate. Overall, these results demonstrate that MFCs can be used to recover anammox bacteria from natural sources, and it may represent a promising bioremediation unit in anaerobic digestor plants for the simultaneous nitrogen removal and electricity generation using digestate as substrate. PMID- 26273610 TI - High Body Mass Index Is an Indicator of Maternal Hypothyroidism, Hypothyroxinemia, and Thyroid-Peroxidase Antibody Positivity during Early Pregnancy. AB - BACKGROUND: Maternal thyroid dysfunction in early pregnancy may increase the risk of adverse pregnancy complications and neurocognitive deficiencies in the developing fetus. Currently, some researchers demonstrated that body mass index (BMI) is associated with thyroid function in nonpregnant population. Hence, the American Thyroid Association recommended screening thyroid function in obese pregnant women; however, the evidence for this is weak. For this purpose, our study investigated the relationship between high BMI and thyroid functions during early pregnancy in Liaoning province, an iodine-sufficient region of China. METHODS: Serum thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb) concentration, urinary iodine concentration (UIC), and BMI were determined in 6303 pregnant women. RESULTS: BMI >= 25 kg/m(2) may act as an indicator of hypothyroxinemia and TPOAb positivity and BMI >= 30 kg/m(2) was associated with increases in the odds of hypothyroidism, hypothyroxinemia, and TPOAb positivity. The prevalence of isolated hypothyroxinemia increased among pregnant women with BMI > 24 kg/m(2). CONCLUSIONS: High BMI during early pregnancy may be an indicator of maternal thyroid dysfunction; for Asian women whose BMI > 24 kg/m(2) and who are within 8 weeks of pregnancy, thyroid functions should be assessed especially. PMID- 26273611 TI - Association between Hyperuricemia and Metabolic Syndrome: An Epidemiological Study of a Labor Force Population in Taiwan. AB - The increasing prevalence of metabolic syndrome (MetS) has become an important issue worldwide. Metabolic comorbidities of hypertension, obesity, and hyperlipidemia are shown as important risk factors for incident gout. The purpose of this study was to investigate the relationship between hyperuricemia and MetS. This is a cross-sectional study. The effective sample included 21,544 individuals who received worker health examinations at a local teaching hospital in Changhua County from 2008~2012. We used multiple logistic regression analysis to investigate the influences of hyperuricemia on MetS. The results showed that individuals with MetS had significantly higher blood pressure, fasting plasma glucose, triglycerides, waist circumference, and high-density lipoprotein cholesterol than those without MetS (P < 0.001). Multiple logistic regression analysis revealed hyperuricemia to be an important factor of MetS. The risk of developing MetS is higher with high levels of serum uric acid (SUA) and the odds ratio (OR) of having MetS is 4.98 times higher for Tertile 3 than for Tertile 1 (95% CI = 4.16-5.97) and 4 times higher for Quartile 4 than for Quartile 1 (95% CI = 3.59-4.46). In conclusion, males are more likely to develop MetS than females, and the risk of having MetS increases with age and SUA concentration. PMID- 26273612 TI - Influence of Leukocyte- and Platelet-Rich Fibrin (L-PRF) in the Healing of Simple Postextraction Sockets: A Split-Mouth Study. AB - The aim of this study was to evaluate the effects of leukocyte- and platelet-rich fibrin (L-PRF) on the pain and soft tissue healing after tooth extractions. Twenty-six patients (9 males and 17 females) were treated with multiple extractions (2 to 8), with a total of 108 extractions. This was an exploratory single blinded randomized clinical trial with a split-mouth design. The pain after the surgery was assessed in each patient by the VAS scale (1 to 10) at intervals of 24-48-72-96 hours. The soft tissue healing was clinically evaluated at 3, 7, 14, and 21 days after surgery by the same examiner surgeon, using the modified Healing Index (4 to 12). The mean value of postextraction pain was 3.2 +/- 0.3 in the experimental sides and 4.1 +/- 0.1 in the control sides. After 7 days from the extractions, the values of modified Healing Index in the experimental and control groups were, respectively, 4.8 +/- 0.6 and 5.1 +/- 0.9. The use of L-PRF in postextraction sockets filling can be proposed as a useful procedure in order to manage the postoperative pain and to promote the soft tissue healing process, reducing the early adverse effects of the inflammation. PMID- 26273613 TI - The Adoption of Smoking and Its Effect on the Mortality Gender Gap in Netherlands: A Historical Perspective. AB - We examine in depth the effect of differences in the smoking adoption patterns of men and women on the mortality gender gap in Netherlands, employing a historical perspective. Using an indirect estimation technique based on observed lung cancer mortality from 1931 to 2012, we estimated lifetime smoking prevalence and smoking attributable mortality. We decomposed the sex difference in life expectancy at birth into smoking-related and nonsmoking-related overall and cause-specific mortality. The smoking epidemic in Netherlands, which started among men born around 1850 and among women from birth cohort 1900 onwards, contributed substantially to the increasing sex difference in life expectancy at birth from 1931 (1.3 years) to 1982 (6.7 years), the subsequent decline to 3.7 years in 2012, and the high excess mortality among Dutch men born between 1895 and 1910. Smoking-related cancer mortality contributed most to the increase in the sex difference, whereas smoking-related cardiovascular disease mortality was mainly responsible for the decline from 1983 onwards. Examining nonsmoking-related (cause-specific) mortality shed new light on the mortality gender gap and revealed the important role of smoking-related cancers, the continuation of excess mortality among women aged 40-50, and a smaller role of biological factors in the sex difference than was previously estimated. PMID- 26273614 TI - Hypoxia-Inducible Factor 1 Is an Inductor of Transcription Factor Activating Protein 2 Epsilon Expression during Chondrogenic Differentiation. AB - The transcription factor AP-2epsilon (activating enhancer-binding protein epsilon) is expressed in cartilage of humans and mice. However, knowledge about regulatory mechanisms influencing AP-2epsilon expression is limited. Using quantitative real time PCR, we detected a significant increase in AP-2epsilon mRNA expression comparing initial and late stages of chondrogenic differentiation processes in vitro and in vivo. Interestingly, in these samples the expression pattern of the prominent hypoxia marker gene angiopoietin-like 4 (Angptl4) strongly correlated with that of AP-2epsilon suggesting that hypoxia might represent an external regulator of AP-2epsilon expression in mammals. In order to show this, experiments directly targeting the activity of hypoxia-inducible factor-1 (HIF1), the complex mediating responses to oxygen deprivation, were performed. While the HIF1-activating compounds 2,2'-dipyridyl and desferrioxamine resulted in significantly enhanced mRNA concentration of AP-2epsilon, siRNA against HIF1alpha led to a significantly reduced expression rate of AP-2epsilon. Additionally, we detected a significant upregulation of the AP-2epsilon mRNA level after oxygen deprivation. In sum, these different experimental approaches revealed a novel role for the HIF1 complex in the regulation of the AP-2epsilon gene in cartilaginous cells and underlined the important role of hypoxia as an important external regulatory stimulus during chondrogenic differentiation modulating the expression of downstream transcription factors. PMID- 26273615 TI - Dimensions of Velopharyngeal Space following Maxillary Advancement with Le Fort I Osteotomy Compared to Zisser Segmental Osteotomy: A Cephalometric Study. AB - The objectives of this study are to assess the velopharyngeal dimensions using cephalometric variables of the nasopharynx and oropharynx as well as to compare the Le Fort I osteotomy technique to Zisser's anterior maxillary osteotomy technique based on patients' outcomes within early and late postoperative follow ups. 15 patients with severe maxillary deficiency treated with Le Fort I osteotomy and maxillary segmental osteotomy were assessed. Preoperative, early postoperative, and late postoperative follow-up lateral cephalograms, patient histories, and operative reports are reviewed with a focus on defined cephalometric landmarks for assessing velopharyngeal space dimension and maxillary movement (measured for three different tracing points). A significant change was found between preoperative and postoperative lateral cephalometric measurements regarding the distance between the posterior nasal spine and the posterior pharyngeal wall in Le Fort I osteotomy cases. However, no significant difference was found between preoperative and postoperative measurements in maxillary segmental osteotomy cases regarding the same measurements. The velopharyngeal area calculated for the Le Fort I osteotomy group showed a significant difference between the preoperative and postoperative measurements. Le Fort I osteotomy for advancement of upper jaw increases velopharyngeal space. On the other hand, Zisser's anterior maxillary segmental osteotomy does not alter the dimension of the velopharyngeal space significantly. PMID- 26273616 TI - Unravelling the RNA-Binding Properties of SAFB Proteins in Breast Cancer Cells. AB - Scaffold attachment factor B1 (SAFB1) and SAFB2 proteins are oestrogen (ER) corepressors that bind to and modulate ER activity through chromatin remodelling or interaction with the basal transcription machinery. SAFB proteins also have an internal RNA-recognition motif but little is known about the RNA-binding properties of SAFB1 or SAFB2. We utilised crosslinking and immunoprecipitation (iCLIP) coupled with high-throughput sequencing to enable a transcriptome-wide mapping of SAFB1 protein-RNA interactions in breast cancer MCF-7 cells. Analysis of crosslinking frequency mapped to transcript regions revealed that SAFB1 binds to coding and noncoding RNAs (ncRNAs). The highest proportion of SAFB1 crosslink sites mapped to ncRNAs, followed by intergenic regions, open reading frames (ORFs), introns, and 3' or 5' untranslated regions (UTR). Furthermore, we reveal that SAFB1 binds directly to RNA and its binding is particularly enriched at purine-rich sequences not dissimilar to the RNA-binding motifs for SR proteins. Using RNAi, we also show, for the first time, that single depletion of either SAFB1 or SAFB2 leads to an increase in expression of the other SAFB protein in both MCF-7 and MDA-MD231 breast cancer cells. PMID- 26273617 TI - Characterization, Microbial Community Structure, and Pathogen Occurrence in Urban Faucet Biofilms in South China. AB - The composition and microbial community structure of the drinking water system biofilms were investigated using microstructure analysis and 454 pyrosequencing technique in Xiamen city, southeast of China. SEM (scanning electron microscope) results showed different features of biofilm morphology in different fields of PVC pipe. Extracellular matrix material and sparse populations of bacteria (mainly rod-shaped and coccoid) were observed. CLSM (confocal laser scanning microscope) revealed different distributions of attached cells, extracellular proteins, alpha-polysaccharides, and beta-polysaccharides. The biofilms had complex bacterial compositions. Differences in bacteria diversity and composition from different tap materials and ages were observed. Proteobacteria was the common and predominant group in all biofilms samples. Some potential pathogens (Legionellales, Enterobacteriales, Chromatiales, and Pseudomonadales) and corrosive microorganisms were also found in the biofilms. This study provides the information of characterization and visualization of the drinking water biofilms matrix, as well as the microbial community structure and opportunistic pathogens occurrence. PMID- 26273618 TI - Can Whole-Body Cryotherapy with Subsequent Kinesiotherapy Procedures in Closed Type Cryogenic Chamber Improve BASDAI, BASFI, and Some Spine Mobility Parameters and Decrease Pain Intensity in Patients with Ankylosing Spondylitis? AB - The present study investigated whether whole-body cryotherapy (WBC) procedures could potentially have more beneficial effects on index of BASDAI and BASFI, pain intensity, and spine mobility parameters: Ott test, modified Schober test, chest expansion in ankylosing spondylitis (AS) patients, than kinesiotherapy procedures used separately. AS patients were exposed to a cycle of WBC procedures lasting 3 minutes a day, with a subsequent 60 minutes of kinesiotherapy or 60 minutes of kinesiotherapy only, for 10 consecutive days excluding weekend. After the completion of the cycle of WBC procedures with subsequent kinesiotherapy in the AS patients, BASDAI index decreased about 40% in comparison with the input value, whereas in the group of patients who received only kinesiotherapy it decreased only about 15% in comparison with the input value. After the completion of the treatment in the WBC group, BASFI index decreased about 30% in comparison with the input value, whereas in the kinesiotherapy group it only decreased about 16% in comparison with the input value. The important conclusion was that, in WBC group with subsequent kinesiotherapy, we observed on average about twice better results than in the group treated only by kinesiotherapy. PMID- 26273619 TI - Fractionated Repetitive Extracorporeal Shock Wave Therapy: A New Standard in Shock Wave Therapy? AB - BACKGROUND: ESWT has proven clinical benefit in dermatology and plastic surgery. It promotes wound healing and improves tissue regeneration, connective tissue disorders, and inflammatory skin diseases. However, a single treatment session or long intervals between sessions may reduce the therapeutic effect. The present study investigated the effects of fractionated repetitive treatment in skin microcirculation. METHODS: 32 rats were randomly assigned to two groups and received either fractionated repetitive high-energy ESWT every ten minutes or placebo shock wave treatment, applied to the dorsal lower leg. Microcirculatory effects were continuously assessed by combined laser Doppler imaging and photospectrometry. RESULTS: In experimental group, cutaneous tissue oxygen saturation was increased 1 minute after the first application and until the end of the measuring period at 80 minutes after the second treatment (P < 0.05). The third ESWT application boosted the effect to its highest extent. Cutaneous capillary blood flow showed a significant increase after the second application which was sustained for 20 minutes after the third application (P < 0.05). Placebo group showed no statistically significant differences. CONCLUSIONS: Fractionated repetitive extracorporeal shock wave therapy (frESWT) boosts and prolongs the effects on cutaneous hemodynamics. The results indicate that frESWT may provide greater benefits in the treatment of distinct soft tissue disorders compared with single-session ESWT. PMID- 26273620 TI - Improvement of BMI after Lifestyle Intervention Is Associated with Normalisation of Elevated ELF Score and Liver Stiffness in Obese Children. AB - BACKGROUND: Noninvasive tools to diagnose nonalcoholic fatty liver disease (NAFLD), including transient elastography (TE) and enhanced liver fibrosis panel (ELF), have only been evaluated in children with biopsy-proven NAFLD. We evaluated the prevalence of ELF and TE abnormalities in obese children without clinical liver disease and examined the effects of BMI stabilization on ELF and TE in a longitudinal approach. METHODS: 39 obese children (17 m, age 12.3 (7.6 17.4) years) who participated in a 12-month lifestyle-intervention program underwent TE and ELF testing at baseline and at completion of the program. Results were compared with data from a nonobese paediatric cohort. RESULTS: TE and ELF at baseline were significantly elevated compared to controls (TE: 5.9 (3.4-8.3) kPa versus 4.45 (2.45-8.85) kPa, P < 0.01; ELF: 9.0 (7.87-9.60) versus 8.6 (7.33-11.52), P = 0.033). All children with elevated TE and ELF results had normal transaminases. After the program, ELF and TE normalized. Reduction of ELF and TE was associated with a decrease in BMI centile. CONCLUSION: Abnormal TE and ELF results in obese children suggest presence of NAFLD even when transaminases are normal. TE and ELF might be used as monitoring tools for NAFLD. BMI stabilisation normalizes TE and ELF, underlining the impact of lifestyle intervention. PMID- 26273622 TI - Statistical Genomic Approach Identifies Association between FSHR Polymorphisms and Polycystic Ovary Morphology in Women with Polycystic Ovary Syndrome. AB - BACKGROUND: Single-nucleotide polymorphisms (SNPs) in the follicle stimulating hormone receptor (FSHR) gene are associated with PCOS. However, their relationship to the polycystic ovary (PCO) morphology remains unknown. This study aimed to investigate whether PCOS related SNPs in the FSHR gene are associated with PCO in women with PCOS. METHODS: Patients were grouped into PCO (n = 384) and non-PCO (n = 63) groups. Genomic genotypes were profiled using Affymetrix human genome SNP chip 6. Two polymorphisms (rs2268361 and rs2349415) of FSHR were analyzed using a statistical approach. RESULTS: Significant differences were found in the allele distributions of the GG genotype of rs2268361 between the PCO and non-PCO groups (27.6% GG, 53.4% GA, and 19.0% AA versus 33.3% GG, 36.5% GA, and 30.2% AA), while no significant differences were found in the allele distributions of the GG genotype of rs2349415. When rs2268361 was considered, there were statistically significant differences of serum follicle stimulating hormone, estradiol, and sex hormone binding globulin between genotypes in the PCO group. In case of the rs2349415 SNP, only serum sex hormone binding globulin was statistically different between genotypes in the PCO group. CONCLUSIONS: Functional variants in FSHR gene may contribute to PCO susceptibility in women with PCOS. PMID- 26273621 TI - Genetic Factors in the Pathogenesis of Nonalcoholic Fatty Liver and Steatohepatitis. AB - Liver fat accumulation generally related to systemic insulin resistance characterizes nonalcoholic fatty liver disease (NAFLD), which in the presence of nonalcoholic steatohepatitis (NASH) can progress towards cirrhosis and hepatocellular carcinoma. Due to the epidemic of obesity, NAFLD is now the most frequent liver disease in Western countries. Epidemiological, familial, and twin studies provide evidence for a strong genetic component of NAFLD susceptibility. Recently, genome-wide association studies led to the identification of the major inherited determinants of hepatic fat accumulation: patatin-like phospholipase domain-containing 3 (PNPLA3) I148M gene and transmembrane 6 superfamily member 2 (TM6SF2) E167K gene variants, involved in lipid droplets remodelling and very low density lipoproteins secretion, are the major determinants of interindividual differences in liver steatosis, and susceptibility to progressive NASH. In this review, we aimed to provide an overview of recent insights into the genetics of hepatic fat accumulation and steatohepatitis. PMID- 26273623 TI - Disorders of MicroRNAs in Peripheral Blood Mononuclear Cells: As Novel Biomarkers of Ankylosing Spondylitis and Provocative Therapeutic Targets. AB - BACKGROUND: MicroRNAs can potentially regulate every aspect of cellular activity. In this study, we investigated whether AS pathogenesis involves microRNAs disorders. RESULT: The expression of 2 microRNAs, hsa-miR-126-3p and hsa-miR-29a, was significantly lower in active AS group before etanercept therapy than in control group. Marched fold changes of them were 3.76 and 16.22. Moreover, expressions of hsa-miR-126-3p and hsa-miR-29a were dramatically upregulated after 12-weeks etanercept treatment. Fold changes were 2.20 and 3.18. All regulations of microRNAs expression mentioned before were statistically significant (fold change >2 and P < 0.05). The expression disorders of the 2 microRNAs did not statistically significantly correlated with BASDAI, CRP, and ESR. CONCLUSION: AS pathogenesis involved dysregulation of microRNAs. Hsa-miR-126-3p and hsa-miR-29a will probably become the potential biomarkers and provocative therapeutic targets of AS. PMID- 26273624 TI - Flap Necrosis after Palatoplasty in Patients with Cleft Palate. AB - Palatal necrosis after palatoplasty in patients with cleft palate is a rare but significant problem encountered by any cleft surgeon. Few studies have addressed this disastrous complication and the prevalence of this problem remains unknown. Failure of a palatal flap may be attributed to different factors like kinking or section of the pedicle, anatomical variations, tension, vascular thrombosis, type of cleft, used surgical technique, surgeon's experience, infection, and malnutrition. Palatal flap necrosis can be prevented through identification of the risk factors and a careful surgical planning should be done before any palatoplasty. Management of severe fistulas observed as a consequence of palatal flap necrosis is a big challenge for any cleft surgeon. Different techniques as facial artery flaps, tongue flaps, and microvascular flaps have been described with this purpose. This review article discusses the current status of this serious complication in patients with cleft palate. PMID- 26273625 TI - The Surgical Treatment Principles of Atlantoaxial Instability Focusing on Rheumatoid Arthritis. AB - OBJECT: This retrospective review was conducted to determine the surgical treatment principle for rheumatoid arthritis (RA) patients with atlantoaxial instability (AAI). METHODS: Thirteen patients with AAI, including 5 RA patients, received preoperative computed tomography- (CT-) based image-guided navigation system (IGS) in C1 lateral mass-C2 pedicle screw-rod system fixation (LC1-PC2 fixation). These 13 patients were analyzed for 52 screws inserted into C1 and C2. We defined these patients as non-RA group (8 patients, 32 screws) and RA group (5 patients, 20 screws). The neurological status for RA group was evaluated using the Ranawat classification. The causes of AAI, surgical indications, complications, surgical method revolution, and CT-based navigation application are discussed. RESULTS: None of the 13 patients expressed neurological function deterioration. The non-RA group screw accuracy was 100%. In the RA group, 1 RA patient developed left C2 screw loosening at 1(+) months after operation due to screw malposition. The screw accuracy for this group was 95%. CONCLUSIONS: Higher intraoperative surgical complication rate was described in RA patients. Preoperative CT-based IGS in LC1-PC2 fixation can provide good neurological function and screw accuracy results. However, for higher screw accuracy in RA patients, intraoperative CT-based IGS application may be considered. PMID- 26273626 TI - SAM68: Signal Transduction and RNA Metabolism in Human Cancer. AB - Alterations in expression and/or activity of splicing factors as well as mutations in cis-acting splicing regulatory sequences contribute to cancer phenotypes. Genome-wide studies have revealed more than 15,000 tumor-associated splice variants derived from genes involved in almost every aspect of cancer cell biology, including proliferation, differentiation, cell cycle control, metabolism, apoptosis, motility, invasion, and angiogenesis. In the past decades, several RNA binding proteins (RBPs) have been implicated in tumorigenesis. SAM68 (SRC associated in mitosis of 68 kDa) belongs to the STAR (signal transduction and activation of RNA metabolism) family of RBPs. SAM68 is involved in several steps of mRNA metabolism, from transcription to alternative splicing and then to nuclear export. Moreover, SAM68 participates in signaling pathways associated with cell response to stimuli, cell cycle transitions, and viral infections. Recent evidence has linked this RBP to the onset and progression of different tumors, highlighting misregulation of SAM68-regulated splicing events as a key step in neoplastic transformation and tumor progression. Here we review recent studies on the role of SAM68 in splicing regulation and we discuss its contribution to aberrant pre-mRNA processing in cancer. PMID- 26273628 TI - Serum Vitamin D and Pyridinoline Cross-Linked Carboxyterminal Telopeptide of Type I Collagen in Patients with Ankylosing Spondylitis. AB - OBJECTIVE: To assess the serum vitamin D and ICTP levels in patients with ankylosing spondylitis (AS) and investigate their relationship with disease activity and bone mineral density (BMD). METHOD: 150 patients and 168 controls were included. Serum 25(OH)D, ICTP, C-reaction protein (CRP), Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), and Hip BMD were assessed in patients. 25(OH)D and ICTP were detected in controls. RESULTS: The serum 25(OH)D in AS was 57.92 +/- 24.42 nmol/L, significantly lower than controls (91.24 +/- 42.02 nmol/L). Serum ICTP in AS was 5.72 +/- 3.88 ug/L, significantly higher than controls (3.69 +/- 1.26 ug/L). ICTP level was higher in men than in women patients (6.07 +/- 4.05 versus 3.84 +/- 1.96 ug/L, P <= 0.01); it was also higher in JAS than in AAS (9.52 +/- 3.79 versus 5.27 +/- 3.65 ug/L, P <= 0.01). Furthermore, 25(OH)D was negatively correlated with ICTP. Low 25(OH)D and high ICTP were one of the reasons of AS patients' low hip BMD. Besides, a significant relationship was found between serum ICTP and CRP. CONCLUSION: There was a high incidence of vitamin D inadequacy in AS. Serum ICTP level was elevated in AS, especially in JAS and male patients. 25(OH)D and ICTP seem to be valuable markers to detect bone loss in AS. PMID- 26273627 TI - Splicing Regulation: A Molecular Device to Enhance Cancer Cell Adaptation. AB - Alternative splicing (AS) represents a major resource for eukaryotic cells to expand the coding potential of their genomes and to finely regulate gene expression in response to both intra- and extracellular cues. Cancer cells exploit the flexible nature of the mechanisms controlling AS in order to increase the functional diversity of their proteome. By altering the balance of splice isoforms encoded by human genes or by promoting the expression of aberrant oncogenic splice variants, cancer cells enhance their ability to adapt to the adverse growth conditions of the tumoral microenvironment. Herein, we will review the most relevant cancer-related splicing events and the underlying regulatory mechanisms allowing tumour cells to rapidly adapt to the harsh conditions they may face during the occurrence and development of cancer. PMID- 26273629 TI - Prevalence and Genotyping of Cryptosporidium Infection in Pet Parrots in North China. AB - Cryptosporidiosis is a worldwide zoonosis caused by Cryptosporidium spp., sometimes leading to severe diarrhea in humans and animals. In the present study, 311 parrots, belonging to four species, namely, Budgerigars (Melopsittacus undulatus), Lovebirds (Agapornis sp.), Alexandrine parakeets (Psittacula eupatria), and Cockatiel (Nymphicus hollandicus), from Beijing and Weifang cities, were examined for Cryptosporidium spp. infection. Blood samples of each bird were examined using enzyme linked immunosorbent assay (ELISA) and fecal samples were examined by Sheather's sugar flotation technique. Prevalence of Cryptosporidium infection were 3.22% (10/311) and 0.64% (2/311) by ELISA and Sheather's sugar flotation technique, respectively. Seroprevalence of Cryptosporidium infection in different breeds varied from 0 to 15.39%. Sequencing analysis showed that both positive samples from fecal samples belonged to Cryptosporidium avian genotype V. This is the first report of Cryptosporidium avian genotype V in Budgerigars. The results of the present study provided foundation-data for prevention and control of cryptosporidiosis in pet birds in China. PMID- 26273630 TI - Comparison of National Institutes of Health-Chronic Prostatitis Symptom Index with International Index of Erectile Function 5 in Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Large Cross-Sectional Study in China. AB - The purpose of the study is to evaluate the relationship between NIH-CPSI and IIEF-5 in Chinese men with CP/CPPS. A large cross-sectional and multicenter survey was conducted from July 2012 to January 2014. Men were recruited from urology clinics which were located at the five cities in China. All men participated in the survey by completing a verbal questionnaire (consisted of sociodemographics, past medical history, sexual history, and self-estimated scales). The results showed that 1,280 men completed the survey. Based on the CP/CPPS definition, a total of 801 men were diagnosed as having CP/CPPS. Men with CP/CPPS reported higher scores of NIH-CPSI and lower scores of IIEF-5 than men without CP/CPPS. NIH-CPSI scores were significantly negatively correlated with IIEF-5 scores. The total scores of NIH-CPSI were significantly more strongly correlated with question 5 than other questions of IIEF-5. The total scores of IIEF-5 were significantly more strongly correlated with pain symptoms scores of NIH-CPSI. Strongest correlation was found between QoL impact and question 5 of IIEF-5. The findings suggested that NIH-CPSI scores were significantly negatively correlated with IIEF-5 scores. Strongest correlation was found between QoL impact and question 5 of IIEF-5. PMID- 26273631 TI - Social Media Use for Public Health Campaigning in a Low Resource Setting: The Case of Waterpipe Tobacco Smoking. AB - INTRODUCTION: Waterpipe tobacco smoking prevalence is increasing worldwide despite its documented health effects. A general belief that it is less harmful than cigarettes may be fuelled by the lack of media campaigns highlighting its health effects. We aimed to create and assess the impact of a social media campaign about dangers of waterpipe smoking. METHODS: The "ShishAware" campaign included three social media (Facebook, Twitter, and YouTube) and a website. Nine months after launch we collected data to assess use of, and reaction to, our media accounts. RESULTS: Requiring limited maintenance resources, Facebook attracted campaign supporters but YouTube attracted opposers. Twitter enabled the most organisation-based contact but Facebook was the most interactive medium. Facebook users were more likely to "like" weekday than weekend statuses and more likely to comment on "shisha fact" than "current affairs" statuses. Follower subscription increased as our posting rate increased. Our YouTube video gained 19,428 views (from all world continents) and 218 comments (86% from pro-waterpipe smokers). CONCLUSIONS: Social media campaigns can be created and maintained relatively easily. They are innovative and have the potential for wide and rapid diffusion, especially towards target audiences. There is a need for more rigorous evaluation of their effects, particularly among the youth. PMID- 26273632 TI - Tobacco and Health Disparities. PMID- 26273633 TI - Low-Rank and Sparse Matrix Decomposition for Genetic Interaction Data. AB - BACKGROUND: Epistatic miniarray profile (EMAP) studies have enabled the mapping of large-scale genetic interaction networks and generated large amounts of data in model organisms. One approach to analyze EMAP data is to identify gene modules with densely interacting genes. In addition, genetic interaction score (S score) reflects the degree of synergizing or mitigating effect of two mutants, which is also informative. Statistical approaches that exploit both modularity and the pairwise interactions may provide more insight into the underlying biology. However, the high missing rate in EMAP data hinders the development of such approaches. To address the above problem, we adopted the matrix decomposition methodology "low-rank and sparse decomposition" (LRSDec) to decompose EMAP data matrix into low-rank part and sparse part. RESULTS: LRSDec has been demonstrated as an effective technique for analyzing EMAP data. We applied a synthetic dataset and an EMAP dataset studying RNA-related processes in Saccharomyces cerevisiae. Global views of the genetic cross talk between different RNA-related protein complexes and processes have been structured, and novel functions of genes have been predicted. PMID- 26273634 TI - Clinical Features in Juvenile-Onset Ankylosing Spondylitis Patients Carrying Different B27 Subtypes. AB - BACKGROUND: Ankylosing spondylitis (AS) is a common rheumatic disease and is characterized by inflammation of the axial skeleton. HLA-B27 is strongly associated with AS. Juvenile-onset AS (JAS) with disease onset before 16 years of age differs from adult-onset AS (AAS) in many respects. OBJECTIVE: To compare the clinical features in JAS with different B27 subtypes and analyze the differences between JAS and AAS. METHODS: 145 JAS and 360 AAS patients were included. The demographic data, clinical manifestations, laboratory markers, Bath AS indices, and B27 subtypes were recorded. RESULTS: Peripheral arthritis, enthesitis, BASDAI, ESR, and CRP were significantly higher in JAS patients with HLA-B(*)2704 than those with B27-negative. Enthesitis and ESR were significantly higher in patients with HLA-B(*)2705 than those with B27-negative. The onset age of HLA B(*)2715 group was much earlier than the other groups. The peripheral arthritis, enthesitis, and hip joint involvement in JAS with HLA-B(*)2704 were significantly higher than those in AAS with HLA-B(*)2704. CONCLUSION: JAS with different B27 subtypes had similar features in most of manifestations; JAS and AAS patients with the same subtype could have distinctive courses. Early diagnosis, hip detection, and control of systemic active inflammation in JAS patients will be helpful for improving the prognosis. PMID- 26273635 TI - In Situ and Home Care Nasopharyngeal Intubation Improves Respiratory Condition and Prevents Surgical Procedures in Early Infancy of Severe Cases of Robin Sequence. AB - AIM: To evaluate the clinical outcome of infants with Robin Sequence (RS) and severe respiratory obstruction managed with nasopharyngeal intubation (NPI). METHODS: This prospective study was conducted with 107 infants with RS admitted to the Hospital for Craniofacial Anomalies of the University of Sao Paulo (HRAC USP), from July 2003 to June 2010, diagnosed with severe RS and treated with NPI. The infants were followed up for the first year of life. Clinical findings, morbidity, and mortality were recorded. RESULTS: Of the 223 infants with RS admitted to the hospital in the period studied, 149 were diagnosed with severe respiratory distress and 107 (71.81%) matched all the inclusion criteria. Of those, 78 (73%) presented Isolated Robin Sequence and 29 (27%) presented other syndromes or anomalies associated with RS. NPI treatment lasted an average of 57 days and the mean hospitalization time was 18 days. Although all infants presented feeding difficulties, 85% were fed orally and only 15% underwent gastrostomy. Morbidity was 14% and no deaths occurred. CONCLUSIONS: The children treated with the RS treatment protocol adopted at the HRAC-USP had improved respiratory and feeding difficulties, required a shorter hospitalization time, and presented low morbidity and mortality during the first year of life. The general outcome prevented surgical procedures in early infancy. PMID- 26273636 TI - Elevated Serum Levels of Soluble CD30 in Ankylosing Spondylitis Patients and Its Association with Disease Severity-Related Parameters. AB - Soluble CD30 (sCD30), a transmembrane glycoprotein that belongs to the tumor necrosis factor receptor (TNFR) superfamily, has been shown to be associated with various pathological conditions. This study was designed to measure the levels of serum sCD30 in patients with ankylosing spondylitis (AS) and to evaluate the relationships between serum sCD30 levels and other disease severity-related indexes, including bath ankylosing spondylitis disease activity index (BASDAI), ankylosing spondylitis disease activity score (ASDAS), and bath ankylosing spondylitis functional index (BASFI). Our results demonstrated significantly elevated sCD30 levels in AS patients compared to healthy controls (HCs) with mean values of 32.0 +/- 12.2 and 24.9 +/- 8.0 ng/mL, respectively (P(**) = 0.007), suggesting a potential role of sCD30 in the pathogenesis of AS. However, no significant correlations of sCD30 with BASDAI, ASDAS, or BASFI were detected in our study (P > 0.05). Therefore, sCD30 cannot be used as a reliable marker for reflecting disease activity and functional ability of AS patients. PMID- 26273637 TI - Network-Based Association Study of Obesity and Type 2 Diabetes with Gene Expression Profiles. AB - The increased prevalence of obesity and type 2 diabetes (T2D) has become an important factor affecting the health of the human. Obesity is commonly considered as a major risk factor for the development of T2D. However, the molecular mechanisms of the disease relations are not well discovered yet. In this study, the combination of multiple differential expression profiles and a comprehensive biological network of obesity and T2D allowed us to identify and compare the disease-responsive active modules and subclusters. The results demonstrated that the connection between obesity and T2D mainly relied on several pathways involved in the digestive metabolism, immunization, and signal transduction, such as adipocytokine, chemokine signaling pathway, T cell receptor signaling pathway, and MAPK signaling pathways. The relationships of almost all of these pathways with obesity and T2D have been verified by the previous reports individually. We also found that the different parts in the same pathway are activated in obesity and T2D. The association of cancer, obesity, and T2D was identified too here. As a conclusion, our network-based method not only gives better support for the close connection between obesity and T2D, but also provides a systemic view in understanding the molecular functions underneath the links. It should be helpful in the development of new therapies for obesity, T2D, and the associated diseases. PMID- 26273638 TI - Second-Hand Smoking among Intermediate and Secondary School Students in Madinah, Saudi Arabia. AB - BACKGROUND AND OBJECTIVES: Second-hand smoke (SHS) is an important public health problem worldwide. The study aimed to estimate the prevalence of SHS exposure and its associated risk factors among intermediate and secondary school students. METHODS: A cross-sectional study was conducted in 2013 among 3400 students from 34 intermediate and secondary schools in Madinah City, Saudi Arabia. Data about sociodemographic and smoking-related factors and SHS exposure were collected using a self-administered questionnaire. RESULTS: Of the 3210 students analyzed, the prevalence of SHS exposure was 32.7% 49.3%, and 25% inside, outside, and both inside and outside the home, respectively. The highest risk of SHS exposure was associated with the adolescent's smoking status, parental smoking, close friends smoking, and family structure. The risk was markedly increased in association with parental smoking for exposure inside the home (OR = 6.49; 95% CI = 5.44 7.73) and with close friends smoking for exposure outside the home (OR = 4.16; 95% CI = 3.54-4.77). The risk of SHS, however, was lower among adolescents having knowledge about smoking and highly educated parents. CONCLUSION: The study revealed a considerably high prevalence of SHS both inside and outside the home among adolescents. Knowledge and beliefs about SHS exposure are the main preventable approach. PMID- 26273639 TI - Emerging Roles of MicroRNAs in EGFR-Targeted Therapies for Lung Cancer. AB - Lung cancer is a leading cause of cancer mortality worldwide. Several molecular pathways underlying mechanisms of this disease have been partly elucidated, among which the epidermal growth factor receptor (EGFR) pathway is one of the well known signaling cascades that plays a critical role in tumorigenesis. Dysregulation of the EGFR signaling is frequently found in lung cancer. The strategies to effectively inhibit EGFR signaling pathway have been mounted for developing anticancer therapeutic agents. However, most anti-EGFR-targeted agents fail to repress cancer progression because of developing drug-resistance. Therefore, studies of the mechanisms underpinning the resistance toward anti-EGFR agents may provide important findings for lung cancer treatment using anti-EGFR therapies. Recently, increasing numbers of miRNAs are correlated with the drug resistance of lung cancer cells to anti-EGFR agents, indicating that miRNAs may serve as novel targets and/or promising predictive biomarkers for anti-EGFR therapy. In this paper, we summarize the emerging role of miRNAs as regulators to modulate the EGFR signaling and the resistance of lung cancer cells to anti-EGFR therapy. We also highlight the evidence supporting the use of miRNAs as biomarkers for response to anti-EGFR agents and as novel therapeutic targets to circumvent the resistance of lung cancer cells to EGFR inhibitors. PMID- 26273640 TI - Weaker Self-Esteem in Adolescence Predicts Smoking. AB - BACKGROUND: To study whether weaker self-esteem in adolescence is connected with smoking behavior in adulthood. METHODS: An age cohort born in 1979 responded to the Lawrence Self-Esteem Questionnaire (LAWSEQ) at the age of 16 (n = 1,072). Respondents' smoking behavior was monitored annually during adolescence and 75.3% (n = 813) of them remained nonsmokers during adolescence. A follow-up questionnaire eliciting smoking behavior was sent to the adolescent nonsmokers at the age of 29 years. Response rate at follow-up was 46.2% (n = 376). RESULTS: Weaker self-esteem (LAWSEQ score >= 3) during the adolescence was not significantly associated with smoking in adulthood. However, those respondents who had weaker self-esteem in adolescence had increased risk of having been smoking regularly (adjusted OR 1.8, 95% CI 1.1-3.0) although not all of them were smokers at the time of the follow-up. CONCLUSIONS: Those with weaker self-esteem in adolescence are more likely to smoke regularly in adulthood. PMID- 26273641 TI - Translational Control Protein 80 Stimulates IRES-Mediated Translation of p53 mRNA in Response to DNA Damage. AB - Synthesis of the p53 tumor suppressor increases following DNA damage. This increase and subsequent activation of p53 are essential for the protection of normal cells against tumorigenesis. We previously discovered an internal ribosome entry site (IRES) that is located at the 5'-untranslated region (UTR) of p53 mRNA and found that the IRES activity increases following DNA damage. However, the mechanism underlying IRES-mediated p53 translation in response to DNA damage is still poorly understood. In this study, we discovered that translational control protein 80 (TCP80) has increased binding to the p53 mRNA in vivo following DNA damage. Overexpression of TCP80 also leads to increased p53 IRES activity in response to DNA damage. TCP80 has increased association with RNA helicase A (RHA) following DNA damage and overexpression of TCP80, along with RHA, leads to enhanced expression of p53. Moreover, we found that MCF-7 breast cancer cells with decreased expression of TCP80 and RHA exhibit defective p53 induction following DNA damage and diminished expression of its downstream target PUMA, a proapoptotic protein. Taken together, our discovery of the function of TCP80 and RHA in regulating p53 IRES and p53 induction following DNA damage provides a better understanding of the mechanisms that regulate IRES-mediated p53 translation in response to genotoxic stress. PMID- 26273642 TI - Impact of Waterpipe Tobacco Pack Health Warnings on Waterpipe Smoking Attitudes: A Qualitative Analysis among Regular Users in London. AB - BACKGROUND: Despite the rise in prevalence of waterpipe tobacco smoking, it has received little legislative enforcement from governing bodies, especially in the area of health warning labels. METHODS: Twenty regular waterpipe tobacco smokers from London took part in five focus groups discussing the impact of waterpipe tobacco pack health warnings on their attitudes towards waterpipe smoking. We presented them with existing and mock waterpipe tobacco products, designed to be compliant with current and future UK/EU legislation. Data were analysed using thematic analysis. RESULTS: Participants felt packs were less attractive and health warnings were more impactful as health warnings increased in size and packaging became less branded. However, participants highlighted their lack of exposure to waterpipe tobacco pack health warnings due to the inherent nature of waterpipe smoking, that is, smoking in a cafe with the apparatus already prepacked by staff. Health warnings at the point of consumption had more reported impact than health warnings at the point of sale. CONCLUSIONS: Waterpipe tobacco pack health warnings are likely to be effective if compliant with existing laws and exposed to end-users. Legislations should be reviewed to extend health warning labels to waterpipe accessories, particularly the apparatus, and to waterpipe-serving premises. PMID- 26273643 TI - Regulation of Cell Cycle Regulators by SIRT1 Contributes to Resveratrol-Mediated Prevention of Pulmonary Arterial Hypertension. AB - Pulmonary arterial hypertension (PAH) is a major cause of morbidity and mortality in rheumatic diseases. Vascular remodeling due to the proliferation of pulmonary arterial smooth muscle cells (PASMCs) is central to the development of PAH. To date, it is still unclear if Silence Information Regulator 1 (SIRT1) regulates cell cycle regulators in the proliferation of PASMCs and contributes to prevention of PAH by resveratrol. In this study, we found that a significant decrease of SIRT1 expression levels in platelet-derived growth factor BB (PDGF BB) treated human PASMCs (HPASMCs) and in monocrotaline (MCT) induced PAH rat. Overexpression of SIRT1 induced G1 phase arrest and increased p21 expression but decreased cyclin D1 expression in PDGF-BB treated HPASMCs. Moreover, resveratrol attenuated pulmonary arterial remodeling, decreased pulmonary arterial pressure, and upregulated SIRT1 and p21 expression but downregulated cyclin D1 expression in MCT induced PAH rat. Notably, knockdown of SIRT1 eliminated the regulation of resveratrol on p21 and cyclin D1 expression in PDGF-BB treated HPASMCs. These results demonstrated that SIRT1 mediated the regulation of resveratrol on the expression of cell cycle regulatory molecules. It suggests that SIRT1 exerts a protective role in PAH associated with rheumatic diseases and can be a potential treatment target. PMID- 26273644 TI - A Minimally Invasive Endoscopic Surgery for Infectious Spondylodiscitis of the Thoracic and Upper Lumbar Spine in Immunocompromised Patients. AB - This study evaluates the safety and effectiveness of computed tomography- (CT-) assisted endoscopic surgery in the treatment of infectious spondylodiscitis of the thoracic and upper lumbar spine in immunocompromised patients. From October 2006 to March 2014, a total of 41 patients with infectious spondylodiscitis underwent percutaneous endoscopic surgery under local anesthesia, and 13 lesions from 13 patients on the thoracic or upper lumbar spine were selected for evaluation. A CT-guided catheter was placed before percutaneous endoscopic surgery as a guide to avoid injury to visceral organs, major vessels, and the spinal cord. All 13 patients had quick pain relief after endoscopic surgery without complications. The bacterial culture rate was 77%. Inflammatory parameters returned to normal after adequate antibiotic treatment. Postoperative radiographs showed no significant kyphotic deformity when compared with preoperative films. As of the last follow-up visit, no recurrent infections were noted. Traditional transthoracic or diaphragmatic surgery with or without posterior instrumentation is associated with high rates of morbidity and mortality, especially in elderly patients, patients with multiple comorbidities, or immunocompromised patients. Percutaneous endoscopic surgery assisted by a CT guided catheter provides a safe and effective alternative treatment for infectious spondylodiscitis of the thoracic and upper lumbar spine. PMID- 26273645 TI - Prediction of MicroRNA-Disease Associations Based on Social Network Analysis Methods. AB - MicroRNAs constitute an important class of noncoding, single-stranded, ~22 nucleotide long RNA molecules encoded by endogenous genes. They play an important role in regulating gene transcription and the regulation of normal development. MicroRNAs can be associated with disease; however, only a few microRNA-disease associations have been confirmed by traditional experimental approaches. We introduce two methods to predict microRNA-disease association. The first method, KATZ, focuses on integrating the social network analysis method with machine learning and is based on networks derived from known microRNA-disease associations, disease-disease associations, and microRNA-microRNA associations. The other method, CATAPULT, is a supervised machine learning method. We applied the two methods to 242 known microRNA-disease associations and evaluated their performance using leave-one-out cross-validation and 3-fold cross-validation. Experiments proved that our methods outperformed the state-of-the-art methods. PMID- 26273646 TI - Bioprecipitation of Calcium Carbonate Crystals by Bacteria Isolated from Saline Environments Grown in Culture Media Amended with Seawater and Real Brine. AB - The precipitation of calcium carbonate and calcium sulphate by isolated bacteria from seawater and real brine obtained in a desalination plant growth in culture media containing seawater and brine as mineral sources has been studied. However, only bioprecipitation was detected when the bacteria were grown in media with added organic matter. Biomineralization process started rapidly, crystal formation taking place in the beginning a few days after inoculation of media; roughly 90% of total cultivated bacteria showed. Six major colonies with carbonate precipitation capacity dominated bacterial community structure cultivated in heterotrophic platable bacteria medium. Taxonomic identification of these six strains through partial 16S rRNA gene sequences showed their affiliation with Gram-positive Bacillus and Virgibacillus genera. These strains were able to form calcium carbonate minerals, which precipitated as calcite and aragonite crystals and showed bacterial fingerprints or bacteria calcification. Also, carbonic anhydrase activity was observed in three of these isolated bacteria. The results of this research suggest that microbiota isolated from sea water and brine is capable of precipitation of carbonate biominerals, which can occur in situ with mediation of organic matter concentrations. Moreover, calcium carbonate precipitation ability of this microbiota could be of importance in bioremediation of CO2 and calcium in certain environments. PMID- 26273647 TI - Quitline Use and Outcomes among Callers with and without Mental Health Conditions: A 7-Month Follow-Up Evaluation in Three States. AB - OBJECTIVES: To examine abstinence outcomes among tobacco users with and without a reported mental health condition (MHC) who enrolled in state tobacco quitline programs. METHODS: Data were analyzed from a 7-month follow-up survey (response rate: 41% [3,132/7,459]) of three state-funded telephone quitline programs in the United States that assessed seven self-reported MHCs at quitline registration. We examined 30-day point prevalence tobacco quit rates for callers with any MHC versus none. Data were weighted to adjust for response bias and oversampling. Multivariable logistic regression was used to examine cessation outcomes. RESULTS: Overall, 45.8% of respondents reported >= 1 MHC; 57.4% of those reporting a MHC reported >= 2 MHCs. The unadjusted quit rate for callers with any MHC was lower than for callers with no MHC (22.0% versus 31.0%, P < 0.001). After adjusting for demographics, nicotine dependence, and program engagement, callers reporting >= 1 MHC were less likely to be abstinent at follow-up (adjusted OR = 0.63, 95% CI = 0.51-0.78, P < 0.001). CONCLUSIONS: More intensive or tailored quitline programs may need to be developed among callers with MHCs as their quit rates appear to be lower than callers without MHCs. PMID- 26273648 TI - Social Inequality in Cigarette Consumption, Cigarette Dependence, and Intention to Quit among Norwegian Smokers. AB - BACKGROUND: The study aim was to examine the influence of education and income on multiple measures of risk of smoking continuation. METHODS: Three logistic regression models were run on cigarette consumption, dependence, and intention to quit based on nationally representative samples (2007-2012) of approximately 1 200 current smokers aged 30-66 years in Norway. RESULTS: The relative risk ratio for current versus never smokers was RRR 5.37, 95% CI [4.26-6.77] among individuals with low educational level versus high and RRR 1.53, 95% CI [1.14 2.06] in the low-income group versus high (adjusted model). Low educational level was associated with high cigarette consumption, high cigarette dependence, and no intention to quit. The difference in predicted probability for having high cigarette consumption, high cigarette dependence, and no intention to quit were in the range of 10-20 percentage points between smokers with low versus those with high educational level. A significant difference between low- and high income levels was observed for intention to quit. The effect of education on high consumption and dependence was mainly found in smokers with high income. CONCLUSION: Increased effort to combat social differences in smoking behaviour is needed. Implementation of smoking cessation programmes with high reach among low socioeconomic groups is recommended. PMID- 26273649 TI - Socioeconomic Gradients in Different Types of Tobacco Use in India: Evidence from Global Adult Tobacco Survey 2009-10. AB - Socioeconomic differences in tobacco use have been reported, but there is a lack of evidence on how they vary according to types of tobacco use. This study explored socioeconomic differences associated with cigarette, bidi, smokeless tobacco (SLT), and dual use (smoking and smokeless tobacco use) in India and tested whether these differences vary by gender and residential area. Secondary analysis of Global Adult Tobacco Survey (GATS) 2009-10 (n = 69,296) was conducted. The primary outcomes were self-reported cigarette, bidi smoking, SLT, and dual use. The main explanatory variables were wealth, education, and occupation. Associations were assessed using multinomial logistic regressions. 69,030 adults participated in the study. Positive association was observed between wealth and prevalence of cigarette smoking while inverse associations were observed for bidi smoking, SLT, and dual use after adjustment for potential confounders. Inverse associations with education were observed for all four types after adjusting for confounders. Significant interactions were observed for gender and area in the association between cigarette, bidi, and smokeless tobacco use with wealth and education. The probability of cigarette smoking was higher for wealthier individuals while the probability of bidi smoking, smokeless tobacco use, and dual use was higher for those with lesser wealth and education. PMID- 26273650 TI - Management of Deep Infection after Instrumentation on Lumbar Spinal Surgery in a Single Institution. AB - Postoperative surgical site infections (SSIs) are more common complications after spinal surgery. SSIs often require extended hospitalisation and may worsen overall clinical outcomes. A retrospective database review of consecutive patients with traditional open lumbar spinal surgery was performed. SSIs patients were identified and reviewed for clinically relevant details, and postoperative SSIs' incidence was calculated for the entire cohort as well as for subgroups with or without spinal implants. In 15 years, 1,176 patients underwent open lumbar spinal surgery with spinal implants and 699 without. Thirty-eight developed postoperative SSIs. Total SSI rate for the entire group was 2.03%. The incidence of postoperative SSIs in the nonimplant group was relatively low. Patients received antibiotics, hyperbaric oxygen therapy, and wet dressing. We provided the precise rates of postoperative SSIs in traditional open spinal surgery obtained from a single-centre data. Patients with spinal implants had higher SSIs' incidence than those without. PMID- 26273651 TI - Nonalcoholic Steatohepatitis: Involvement of the Telomerase and Proinflammatory Mediators. AB - Nonalcoholic steatohepatitis or NASH is an excessive accumulation of fat in hepatocytes accompanied by inflammation and hepatic injury. Proinflammatory molecules such as IL-17, CCL20, S100A8, S100A9, and S100A8/A9 have been shown to be implicated in many types of cancer. Telomerase activity has been found to be associated with chronic inflammation and cancer. NASH can progress to fibrosis then cirrhosis and finally to hepatocellular carcinoma (HCC). Our objective is to try to find a relation between inflammation and the progression of NASH into HCC. We found that there was a significant elevation in the telomerase activity, detected by real-time PCR, between NASH and fibrotic NASH in the liver biopsies of patients. The expression of S100A8, S100A9, S100A8/A9, CCL20, and IL-17, detected by ELISA, is significantly increased in NASH patients with fibrosis in comparison with controls. But, in NASH patients, S100A9, S100A8/A9, and IL-17 only are significantly elevated in comparison with controls. The same, on the mRNA level, expression of IL-17, detected by RT-PCR, is significantly elevated in NASH patients in comparison with controls. Therefore, there is a direct link between the expression of IL-17, CCL20, telomerase, S100A8, and S100A9 in the fibrotic condition and the progression towards cancer. PMID- 26273652 TI - A High Diversity in Chitinolytic and Chitosanolytic Species and Enzymes and Their Oligomeric Products Exist in Soil with a History of Chitin and Chitosan Exposure. AB - Chitin is one of the most abundant biomolecules on earth, and its partially de-N acetylated counterpart, chitosan, is one of the most promising biotechnological resources due to its diversity in structure and function. Recently, chitin and chitosan modifying enzymes (CCMEs) have gained increasing interest as tools to engineer chitosans with specific functions and reliable performance in biotechnological and biomedical applications. In a search for novel CCME, we isolated chitinolytic and chitosanolytic microorganisms from soils with more than ten-years history of chitin and chitosan exposure and screened them for chitinase and chitosanase isoenzymes as well as for their patterns of oligomeric products by incubating their secretomes with chitosan polymers. Of the 60 bacterial strains isolated, only eight were chitinolytic and/or chitosanolytic, while 20 out of 25 fungal isolates were chitinolytic and/or chitosanolytic. The bacterial isolates produced rather similar patterns of chitinolytic and chitosanolytic enzymes, while the fungal isolates produced a much broader range of different isoenzymes. Furthermore, diverse mixtures of oligosaccharides were formed when chitosan polymers were incubated with the secretomes of select fungal species. Our study indicates that soils with a history of chitin and chitosan exposure are a good source of novel CCME for chitosan bioengineering. PMID- 26273653 TI - Lipid Emulsion Attenuates Acetylcholine-Induced Relaxation in Isolated Rat Aorta. AB - We investigated the effect of Lipofundin MCT/LCT and Intralipid on acetylcholine induced nitric oxide- (NO-) mediated relaxation in rat aorta to determine which lipid emulsion (LE) is more potent in terms of inhibition of NO-induced relaxation. Dose-response curves of responses induced by acetylcholine, the calcium ionophore A23187, and sodium nitroprusside were generated using isolated rat aorta with or without LE. The effect of Lipofundin MCT/LCT on acetylcholine induced endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein endothelial cells (HUVECs) was investigated using western blotting. Lipofundin MCT/LCT (0.1 and 0.2%) attenuated acetylcholine-induced relaxation in endothelium-intact aorta with or without tiron, whereas 0.2% Intralipid only inhibited relaxation. Lipofundin MCT/LCT inhibited relaxation induced by the calcium ionophore A23187 and sodium nitroprusside in endothelium intact aorta, but Lipofundin MCT/LCT had no effect on sodium nitroprusside induced relaxation in the endothelium-denuded aorta. Combined pretreatment with l arginine plus Lipofundin MCT/LCT increased acetylcholine-induced maximal relaxation in endothelium-intact aorta compared with Lipofundin MCT/LCT alone. L Arginine attenuated Lipofundin MCT/LCT-mediated inhibition of acetylcholine induced eNOS phosphorylation in HUVECs. Taken together, Lipofundin MCT/LCT attenuated acetylcholine-induced NO-mediated relaxation via an inhibitory effect on the endothelium including eNOS, which is proximal to activation of guanylyl cyclase. PMID- 26273654 TI - Predictive Factors of Clinical Response of Infliximab Therapy in Active Nonradiographic Axial Spondyloarthritis Patients. AB - OBJECTIVES: To evaluate the efficiency and the predictive factors of clinical response of infliximab in active nonradiographic axial spondyloarthritis patients. METHODS: Active nonradiographic patients fulfilling ESSG criteria for SpA but not fulfilling modified New York criteria were included. All patients received infliximab treatment for 24 weeks. The primary endpoint was ASAS20 response at weeks 12 and 24. The abilities of baseline parameters and response at week 2 to predict ASAS20 response at weeks 12 and 24 were assessed using ROC curve and logistic regression analysis, respectively. RESULTS: Of 70 axial SpA patients included, the proportions of patients achieving an ASAS20 response at weeks 2, 6, 12, and 24 were 85.7%, 88.6%, 87.1%, and 84.3%, respectively. Baseline MRI sacroiliitis score (AUC = 0.791; P = 0.005), CRP (AUC = 0.75; P = 0.017), and ASDAS (AUC = 0.778, P = 0.007) significantly predicted ASAS20 response at week 12. However, only ASDAS (AUC = 0.696, P = 0.040) significantly predicted ASAS20 response at week 24. Achievement of ASAS20 response after the first infliximab infusion was a significant predictor of subsequent ASAS20 response at weeks 12 and 24 (wald chi(2) = 6.87, P = 0.009, and wald chi(2) = 5.171, P = 0.023). CONCLUSIONS: Infliximab shows efficiency in active nonradiographic axial spondyloarthritis patients. ASDAS score and first-dose response could help predicting clinical efficacy of infliximab therapy in these patients. PMID- 26273655 TI - MUTYH Gene Polymorphisms as Risk Factors for Rheumatoid Arthritis. AB - OBJECTIVES: MUTYH glycosylase involved in DNA repair pathways may be associated with the risk of autoimmune diseases such as rheumatoid arthritis (RA). Therefore, the association between polymorphisms in the MUTYH gene and RA was evaluated. METHODS: We recruited 192 RA patients and 192 healthy subjects in Taiwan. The 4 MUTYH polymorphisms (rs3219463, rs3219476, rs3219489, and rs3219493) were detected and haplotype analysis was performed using the Bayesian method. The genotype and allelic frequency distributions of the polymorphisms in both RA patients and healthy patients were compared by the chi-square test. RESULTS: Comparison of the genotype/allele frequencies between individuals with RA and the control groups revealed significant differences in 2 MUTYH gene polymorphisms, rs3219463 and rs3219476. After we performed a haplotype-specific analysis, the haplotypes Ht6-GTGC and Ht8-GGCG had lower presenting rates in RA patients than in the control groups. Furthermore, the genotype frequency of rs3219463 G/ was significantly increased among patients with immunoglobulin M rheumatoid factors, whereas that of rs3219476 was not. CONCLUSION: We demonstrated that the rs3219463 and rs3219476 polymorphisms in RA patients from a Taiwan Chinese population were associated with disease susceptibility. These data indicate that the MUTYH gene may play a role in the progression of RA. PMID- 26273656 TI - Fructose-Drinking Water Induced Nonalcoholic Fatty Liver Disease and Ultrastructural Alteration of Hepatocyte Mitochondria in Male Wistar Rat. AB - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the complications of the metabolic syndrome. It encompasses a wide range of disease spectrum from simple steatosis to liver cirrhosis. Structural alteration of hepatic mitochondria might be involved in the pathogenesis of NAFLD. AIMS: In the present study, we used a newly established model of fructose-induced metabolic syndrome in male Wistar rats in order to investigate the ultrastructural changes in hepatic mitochondria that occur with fructose consumption and their association with NAFLD pathogenesis. METHODS: The concentration of fructose-drinking water (FDW) used in this study was 20%. Six male Wistar rats were supplemented with FDW 20% for eight weeks. Body composition and metabolic parameters were measured before and after 8 weeks of FDW 20%. Histomorphology of the liver was evaluated and ultrastructural changes of mitochondria were assessed with transmission electron micrograph. RESULTS: After 8 weeks of fructose consumption, the animals developed several features of the metabolic syndrome. Moreover, fructose consumption led to the development of macrovesicular hepatic steatosis and mitochondrial ultrastructural changes, such as increase in mitochondrial size, disruption of the cristae, and reduction of matrix density. CONCLUSION: We conclude that in male Wistar rat 8-week consumption of FDW 20% leads to NAFLD likely via mitochondrial structural alteration. PMID- 26273657 TI - Posttranscriptional Regulation and RNA Binding Proteins in Cancer Biology. PMID- 26273658 TI - Deciphering the Correlation between Breast Tumor Samples and Cell Lines by Integrating Copy Number Changes and Gene Expression Profiles. AB - Breast cancer is one of the most common cancers with high incident rate and high mortality rate worldwide. Although different breast cancer cell lines were widely used in laboratory investigations, accumulated evidences have indicated that genomic differences exist between cancer cell lines and tissue samples in the past decades. The abundant molecular profiles of cancer cell lines and tumor samples deposited in the Cancer Cell Line Encyclopedia and The Cancer Genome Atlas now allow a systematical comparison of the breast cancer cell lines with breast tumors. We depicted the genomic characteristics of breast primary tumors based on the copy number variation and gene expression profiles and the breast cancer cell lines were compared to different subgroups of breast tumors. We identified that some of the breast cancer cell lines show high correlation with the tumor group that agrees with previous knowledge, while a big part of them do not, including the most used MCF7, MDA-MB-231, and T-47D. We presented a computational framework to identify cell lines that mostly resemble a certain tumor group for the breast tumor study. Our investigation presents a useful guide to bridge the gap between cell lines and tumors and helps to select the most suitable cell line models for personalized cancer studies. PMID- 26273659 TI - Effect of Intraoperative Corneal Stromal Pocket Irrigation in Small Incision Lenticule Extraction. AB - This study aimed at evaluating the effect of intraoperative corneal pocket irrigation in small incision lenticule extraction (SMILE) and compares it to that in femtosecond laser-assisted in situ keratomileusis (FS-LASIK). Sixteen rabbit eyes underwent a SMILE procedure, with 8 eyes having corneal pocket irrigation, while the other 8 eyes were without irrigation. Another 16 eyes underwent a FS LASIK procedure for comparison, with 8 eyes having flap irrigation, while the other 8 eyes were without irrigation. The results showed that the changes in the total corneal thickness, anterior and posterior lamellar thickness, measured by the anterior segment optical coherence tomography, were comparable between the SMILE with and without irrigation groups, suggesting that the irrigation did not lead to significant changes in the corneal thickness. However, at postoperative 8 hours, in vivo confocal microscopy showed that the interface reflectivity in the SMILE with irrigation group was significantly higher than that in other three groups. The presence of interface fluid was further confirmed by the identification of fluid pockets with undulated collagen shown on histological section in the post-SMILE with irrigation eyes. Our findings might contribute to the occurrence of post-SMILE delayed immediate visual quality recovery and further clinical study is required. PMID- 26273660 TI - Analysis of Erythrocyte C4d to Complement Receptor 1 Ratio: Use in Distinguishing between Infection and Flare-Up in Febrile Patients with Systemic Lupus Erythematosus. AB - OBJECTIVE: Fever in systemic lupus erythematosus (SLE) can be caused by infection or flare-up of the disease. This study aimed to determine whether the ratio of the level of erythrocyte-bound C4d to that of complement receptor 1 (C4d/CR1) can serve as a useful biomarker in the differentiation between infection and flare-up in febrile SLE patients. METHODS: We enrolled febrile SLE patients and determined the ratio on the day of admission. The patients were divided into 2 groups according to the subsequent clinical course. RESULTS: Among the febrile SLE patients, those with flare-up had higher ratios and lower C-reactive protein (CRP) levels than those with infection. Cut-off values of <1.2447 and >4.67 for C4d/CR1 ratio and CRP, respectively, were 40.91% sensitive and 100.0% specific for the presence of infection in febrile SLE patients; similarly, cut-off values of >1.2447 and <2.2, respectively, were 80% sensitive and 100% specific for the absence of infection in febrile SLE patients. CONCLUSION: The C4d/CR1 ratio is a simple and quickly determinable biomarker that enables the differentiation between infection and flare-up in febrile SLE patients at initial evaluation. Further, when combined with the CRP level, it is useful to evaluate disease activity in SLE patients with infection. PMID- 26273661 TI - Bacterial Diversity and Bioremediation Potential of the Highly Contaminated Marine Sediments at El-Max District (Egypt, Mediterranean Sea). AB - Coastal environments worldwide are threatened by the effects of pollution, a risk particularly high in semienclosed basins like the Mediterranean Sea that is poorly studied from bioremediation potential perspective especially in the Southern coast. Here, we investigated the physical, chemical, and microbiological features of hydrocarbon and heavy metals contaminated sediments collected at El Max bay (Egypt). Molecular and statistical approaches assessing the structure of the sediment-dwelling bacterial communities showed correlations between the composition of bacterial assemblages and the associated environmental parameters. Fifty strains were isolated on mineral media supplemented by 1% crude oil and identified as a diverse range of hydrocarbon-degrading bacteria involved in different successional stages of biodegradation. We screened the collection for biotechnological potential studying biosurfactant production, biofilm formation, and the capability to utilize different hydrocarbons. Some strains were able to grow on multiple hydrocarbons as unique carbon source and presented biosurfactant like activities and/or capacity to form biofilm and owned genes involved in different detoxification/degradation processes. El-Max sediments represent a promising reservoir of novel bacterial strains adapted to high hydrocarbon contamination loads. The potential of the strains for exploitation for in situ intervention to combat pollution in coastal areas is discussed. PMID- 26273662 TI - Association of the Genetic Polymorphisms in Transcription Factor 7-Like 2 and Peroxisome Proliferator-Activated Receptors- gamma 2 with Type 2 Diabetes Mellitus and is Interaction with Obesity Status in Emirati Population. AB - BACKGROUND: Transcription factor 7-like 2 gene (TCF7L2) and peroxisome proliferator-activated receptors-gamma2 (PPAR-gamma2) have a profound effect on the incidence of type 2 diabetes mellitus (T2DM) and had previously been found to be associated with T2DM risk in various ppopulations. However, studies in the Arab population are inconsistent. We conducted a case control study to confirm the association of variants rs10885409 of TCF7L2 and Pro12Ala (rs1801282) of PPAR gamma2 with risk of T2DM and related complications in Emirati population of Arab origin. We also investigated the interaction of these associations with obesity status. METHODS: DNA was extracted from the saliva samples of 272 T2DM patients and 216 nondiabetic Emiratis. Genotyping for rs10885409 (TCF7L2) and rs1801282 (PPAR-gamma2 P12A) variants was accomplished with a TaqMan assay. The subgroups were constituted according to obesity status. RESULTS: In the nonobese group, the rs10885409 C allele in the recessive model was significantly associated with the incidence of T2DM (OR 1.975 [95% CI 1.127-3.461], P = 0.017), but this association was not observed in the obese group or when BMI was not considered. PPAR-gamma2 risk allele Pro12 frequency (0.96) was similar in the groups tested and more than 90% population was homozygous for this allele. CONCLUSIONS: Our case-control study is the first of its kind in Emiratis which establishes TCF7L2 rs10885409 C allele as a T2DM risk factor in Emiratis and this association is modulated by obesity status. We also confirmed that Pro12Ala mutation in PPAR gamma2 is not associated with T2DM risk in this population. PMID- 26273663 TI - Study of Protein Biomarkers of Diabetes Mellitus Type 2 and Therapy with Vitamin B1. AB - In the present research work, the levels of protein biomarkers specific to diabetes mellitus type 2 in the Pakistani population using proteomic technology have been identified and characterized and effect of high dose thiamine has been seen on the levels of these marker proteins. Diabetic patients and normal healthy controls were recruited from the Sheikh Zayed Hospital, Lahore, Pakistan. Total biochemical assays and proteins were estimated by modern proteomic techniques. Some proteins were up- and downregulated in diabetic samples as compared to control and decreased after thiamine therapy, while other protein markers did not show a significant change after the thiamine therapy. The effect of high dose thiamine on the levels of these identified protein biomarkers in the human urine has also been observed. Assessment of the levels of these biomarkers will be helpful in not only early diagnosis but also prognosis of diabetes mellitus type 2. PMID- 26273665 TI - Wide-Field Megahertz OCT Imaging of Patients with Diabetic Retinopathy. AB - PURPOSE: To evaluate the feasibility of wide-field Megahertz (MHz) OCT imaging in patients with diabetic retinopathy. METHODS: A consecutive series of 15 eyes of 15 patients with diagnosed diabetic retinopathy were included. All patients underwent Megahertz OCT imaging, a close clinical examination, slit lamp biomicroscopy, and funduscopic evaluation. To acquire densely sampled, wide-field volumetric datasets, an ophthalmic 1050 nm OCT prototype system based on a Fourier-domain mode-locked (FDML) laser source with 1.68 MHz A-scan rate was employed. RESULTS. We were able to obtain OCT volume scans from all included 15 patients. Acquisition time was 1.8 seconds. Obtained volume datasets consisted of 2088 * 1044 A-scans of 60 degrees of view. Thus, reconstructed en face images had a resolution of 34.8 pixels per degree in x-axis and 17.4 pixels per degree. Due to the densely sampled OCT volume dataset, postprocessed customized cross sectional B-frames through pathologic changes such as an individual microaneurysm or a retinal neovascularization could be imaged. CONCLUSIONS: Wide-field Megahertz OCT is feasible to successfully image patients with diabetic retinopathy at high scanning rates and a wide angle of view, providing information in all three axes. The Megahertz OCT is a useful tool to screen diabetic patients for diabetic retinopathy. PMID- 26273664 TI - Glycemic Variability Assessed by Continuous Glucose Monitoring and Short-Term Outcome in Diabetic Patients Undergoing Percutaneous Coronary Intervention: An Observational Pilot Study. AB - Poor glycemic control is associated with unfavorable outcome in patients undergoing percutaneous coronary intervention (PCI), irrespective of diabetes mellitus. However a complete assessment of glycemic status may not be fully described by glycated hemoglobin or fasting blood glucose levels, whereas daily glycemic fluctuations may influence cardiovascular risk and have even more deleterious effects than sustained hyperglycemia. Thus, this paper investigated the effectiveness of a continuous glucose monitoring (CGM), registering the mean level of glycemic values but also the extent of glucose excursions during coronary revascularization, in detecting periprocedural outcome such as renal or myocardial damage, assessed by serum creatinine, neutrophil gelatinase-associated lipocalin (NGAL), and troponin I levels. High glycemic variability (GV) has been associated with worse postprocedural creatinine and NGAL variations. Moreover, GV, and predominantly hypoglycemic variations, has been observed to increase in patients with periprocedural myocardial infarction. Thus, our study investigated the usefulness of CGM in the setting of PCI where an optimal glycemic control should be achieved in order to prevent complications and improve outcome. PMID- 26273666 TI - Association of Metabolic Syndrome with the Cardioankle Vascular Index in Asymptomatic Korean Population. AB - AIM: Metabolic syndrome is characterized by a cluster of atherosclerotic cardiovascular risk factors. The cardioankle vascular index (CAVI) reflects arterial stiffness and may be used as an indicator of atherosclerotic cardiovascular disease. In this study, we investigated the association of CAVI with metabolic syndrome. METHODS: A total of 1,144 adults were included in this study. We measured CAVIs and examined blood samples to identify metabolic syndrome according to WHO Asia Pacific criteria and NCEP-ATPIII criteria. AST, ALT, r-GTP, BUN, creatinine, high sensitivity C-reactive protein, and uric acid were also measured. RESULTS: CAVI values were significantly higher in subjects with metabolic syndrome than those without metabolic syndrome and increased according to the number of metabolic syndrome components present. Subjects with high fasting blood sugar levels or high blood pressure showed high CAVI values. Multiple regression analysis showed that age, sex, diastolic blood pressure, and uric acid were independent predictors of CAVI. CONCLUSION: Subjects with metabolic syndrome had high CAVIs, which indicated arterial stiffness, and were closely associated with an increase in the number of metabolic risk factors. The individual risk factors for metabolic syndrome have the synergistic effect of elevating arterial stiffness in asymptomatic Korean population. PMID- 26273667 TI - Recent Trends in Therapeutic Approaches for Diabetes Management: A Comprehensive Update. AB - Diabetes highlights a growing epidemic imposing serious social economic crisis to the countries around the globe. Despite scientific breakthroughs, better healthcare facilities, and improved literacy rate, the disease continues to burden several sections, especially middle and low income countries. The present trends indicate the rise in premature death, posing a major threat to global development. Scientific and technological advances have witnessed the development of newer generation of drugs like sulphonylureas, biguanides, alpha glucosidase inhibitors, and thiazolidinediones with significant efficacy in reducing hyperglycemia. Recent approaches in drug discovery have contributed to the development of new class of therapeutics like Incretin mimetics, Amylin analogues, GIP analogs, Peroxisome proliferator activated receptors, and dipeptidyl peptidase-4 inhibitor as targets for potential drugs in diabetes treatment. Subsequently, the identification and clinical investigation of bioactive substances from plants have revolutionized the research on drug discovery and lead identification for diabetes management. With a focus on the emerging trends, the review article explores the current statistical prevalence of the disease, discussing the benefits and limitations of the commercially available drugs. Additionally, the critical areas in clinical diabetology are discussed, with respect to prospects of statins, nanotechnology, and stem cell technology as next generation therapeutics and why the herbal formulations are consistently popular choice for diabetes medication and management. PMID- 26273668 TI - Population-Based Studies on the Epidemiology of Insulin Resistance in Children. AB - BACKGROUND: In view of the alarming incidence of obesity in children, insight into the epidemiology of the prediabetic state insulin resistance (IR) seems important. Therefore, the aim of this systematic review was to give an overview of all population-based studies reporting on the prevalence and incidence rates of IR in childhood. METHODS: PubMed, Embase, and Cochrane library were searched in order to find all available population-based studies describing the epidemiology of IR in pediatric populations. Prevalence rates together with methods and cut-off values used to determine IR were extracted and summarized with weight and sex specific prevalence rates of IR if available. RESULTS: Eighteen population-based studies were identified, describing prevalence rates varying between 3.1 and 44%, partly explained by different definitions for IR. Overweight and obese children had higher prevalence rates than normal weight children. In seven out of thirteen studies reporting sex specific results, girls seemed to be more affected than boys. CONCLUSION: Prevalence rates of IR reported in children vary widely which is partly due to the variety of definitions used. Overweight and obese children had higher prevalence and girls were more insulin resistant than boys. Consensus on the definition for IR in children is needed to allow for comparisons between different studies. PMID- 26273669 TI - Dysglycaemia and Other Predictors for Progression or Regression from Impaired Fasting Glucose to Diabetes or Normoglycaemia. AB - AIMS: Diabetes mellitus is a growing health problem worldwide. This study aimed to describe dysglycaemia and determine the impact of body composition and clinical and lifestyle factors on the risk of progression or regression from impaired fasting glucose (IFG) to diabetes or normoglycaemia in Australian women. METHODS: This study included 1167 women, aged 20-94 years, enrolled in the Geelong Osteoporosis Study. Multivariable logistic regression was used to identify predictors for progression to diabetes or regression to normoglycaemia (from IFG), over 10 years of follow-up. RESULTS: At baseline the proportion of women with IFG was 33.8% and 6.5% had diabetes. Those with fasting dysglycaemia had higher obesity-related factors, lower serum HDL cholesterol, and lower physical activity. Over a decade, the incidence of progression from IFG to diabetes was 18.1 per 1,000 person-years (95% CI, 10.7-28.2). Fasting plasma glucose and serum triglycerides were important factors in both progression to diabetes and regression to normoglycaemia. CONCLUSIONS: Our results show a transitional process; those with IFG had risk factors intermediate to normoglycaemics and those with diabetes. This investigation may help target interventions to those with IFG at high risk of progression to diabetes and thereby prevent cases of diabetes. PMID- 26273670 TI - The Genetic Profile from HLA and Non-HLA Loci Allows Identification of Atypical Type 2 Diabetes Patients. AB - The complex diagnosis and treatment of diabetes highlight the need for markers to define how to monitor patients correctly during the course of their disease. Different studies demonstrate the existence of patients who cannot be clearly classified. We have previously shown that it is possible to differentiate "atypical diabetic patients" based on genotyping the HLA. In this work we show that the analysis of non-HLA related to type 1 diabetes in the INS-VNTR, SNP rs689, and rs3842753 improves the identification of these patients. We genotyped 913 individuals comprising controls from the general population and "classic" and "atypical" diabetic patients. We compared the distribution of these loci and analyzed linkage disequilibrium. The haplotype was in LD for all the SNPs that were evaluated. Regarding their association with the disease, the haplotype IAC was associated with type 1 (odds 2.60, 1.82-3.72, CI 95%) and "atypical diabetes" (odds 1.50, 1.01-2.23, CI 95%), whereas we did not observe an association with type 2 diabetes. Therefore, our results confirm that atypical diabetes is a different entity of the disease where the patient presents with a genetic background of T1D and a T2D phenotype, findings that are likely to be relevant for patient diagnosis and management in the clinic. PMID- 26273671 TI - GDF-15 as a Target and Biomarker for Diabetes and Cardiovascular Diseases: A Translational Prospective. AB - Growth differentiation factor-15 (GDF-15) is a stress responsive cytokine. It is highly expressed in cardiomyocytes, adipocytes, macrophages, endothelial cells, and vascular smooth muscle cells in normal and pathological condition. GDF-15 increases during tissue injury and inflammatory states and is associated with cardiometabolic risk. Increased GDF-15 levels are associated with cardiovascular diseases such as hypertrophy, heart failure, atherosclerosis, endothelial dysfunction, obesity, insulin resistance, diabetes, and chronic kidney diseases in diabetes. Increased GDF-15 level is linked with the progression and prognosis of the disease condition. Age, smoking, and environmental factors are other risk factors that may increase GDF-15 level. Most of the scientific studies reported that GDF-15 plays a protective role in different tissues. However, few reports show that the deficiency of GDF-15 is beneficial against vascular injury and inflammation. GDF-15 protects heart, adipose tissue, and endothelial cells by inhibiting JNK (c-Jun N-terminal kinase), Bad (Bcl-2-associated death promoter), and EGFR (epidermal growth factor receptor) and activating Smad, eNOS, PI3K, and AKT signaling pathways. The present review describes the different animal and clinical studies and patent updates of GDF-15 in diabetes and cardiovascular diseases. It is a challenge for the scientific community to use GDF-15 information for patient monitoring, clinical decision-making, and replacement of current treatment strategies for diabetic and cardiovascular diseases. PMID- 26273672 TI - NLRP3 Inflammasome Polymorphism and Macrovascular Complications in Type 2 Diabetes Patients. AB - BACKGROUND: It is generally accepted that poor glycemic control, arterial hypertension and/or hyperlipidemia, and the associated oxidative stress may contribute to the development of macro- and microvascular complications in type 2 diabetes (T2D). Such metabolic damage signals may activate inflammasome and trigger chronic inflammation. We investigated common polymorphisms in inflammasome coding genes and the risk for macro- and microvascular complications in T2D. METHODS: In total 181 clinically well-characterised T2D patients were genotyped for NLRP3 rs35829419 and CARD8 rs2043211. Risk for diabetic complications was assessed using logistic regression. RESULTS: Patients with median duration of T2D 11 (6-17) years had relatively well controlled blood glucose and lipid levels and blood pressure on the prescribed treatment regimen. Duration of T2D and plasma cholesterol levels were the most important clinical risk factors for macrovascular complications (P = 0.007 and P = 0.031). NLRP3 rs35829419 was associated with increased risk for macrovascular complications (P = 0.004), with myocardial infarction in particular (P = 0.052). No association was observed between CARD8 polymorphism and any of T2D complications. CONCLUSIONS: Our preliminary data suggest the role of NLRP3 polymorphism in diabetic macrovascular complications, especially in myocardial infarction. PMID- 26273673 TI - Comment on "Alpha-Lipoic Acid and Antioxidant Diet Help to Improve Endothelial Dysfunction in Adolescents with Type 1 Diabetes: A Pilot Trial". PMID- 26273674 TI - Edible Bird's Nest Prevents High Fat Diet-Induced Insulin Resistance in Rats. AB - Edible bird's nest (EBN) is used traditionally in many parts of Asia to improve wellbeing, but there are limited studies on its efficacy. We explored the potential use of EBN for prevention of high fat diet- (HFD-) induced insulin resistance in rats. HFD was given to rats with or without simvastatin or EBN for 12 weeks. During the intervention period, weight measurements were recorded weekly. Blood samples were collected at the end of the intervention and oral glucose tolerance test conducted, after which the rats were sacrificed and their liver and adipose tissues collected for further studies. Serum adiponectin, leptin, F2-isoprostane, insulin, and lipid profile were estimated, and homeostatic model assessment of insulin resistance computed. Effects of the different interventions on transcriptional regulation of insulin signaling genes were also evaluated. The results showed that HFD worsened metabolic indices and induced insulin resistance partly through transcriptional regulation of the insulin signaling genes. Additionally, simvastatin was able to prevent hypercholesterolemia but promoted insulin resistance similar to HFD. EBN, on the other hand, prevented the worsening of metabolic indices and transcriptional changes in insulin signaling genes due to HFD. The results suggest that EBN may be used as functional food to prevent insulin resistance. PMID- 26273675 TI - Healthy Chilean Adolescents with HOMA-IR >= 2.6 Have Increased Cardiometabolic Risk: Association with Genetic, Biological, and Environmental Factors. AB - OBJECTIVE: To determine the optimal cutoff of the homeostasis model assessment insulin resistance (HOMA-IR) for diagnosis of the metabolic syndrome (MetS) in adolescents and examine whether insulin resistance (IR), determined by this method, was related to genetic, biological, and environmental factors. METHODS: In 667 adolescents (16.8 +/- 0.3 y), BMI, waist circumference, glucose, insulin, adiponectin, diet, and physical activity were measured. Fat and fat-free mass were assessed by dual-energy X-ray absorptiometry. Family history of type 2 diabetes (FHDM) was reported. We determined the optimal cutoff of HOMA-IR to diagnose MetS (IDF criteria) using ROC analysis. IR was defined as HOMA-IR values above the cutoff. We tested the influence of genetic, biological, and environmental factors on IR using logistic regression analyses. RESULTS: Of the participants, 16% were obese and 9.4 % met criteria for MetS. The optimal cutoff for MetS diagnosis was a HOMA-IR value of 2.6. Based on this value, 16.3% of participants had IR. Adolescents with IR had a significantly higher prevalence of obesity, abdominal obesity, fasting hyperglycemia, and MetS compared to those who were not IR. FHDM, sarcopenia, obesity, and low adiponectin significantly increased the risk of IR. CONCLUSIONS: In adolescents, HOMA-IR >= 2.6 was associated with greater cardiometabolic risk. PMID- 26273676 TI - Comparative Evaluation of Two Venous Sampling Techniques for the Assessment of Pancreatic Insulin and Zinc Release upon Glucose Challenge. AB - Advances in noninvasive imaging modalities have provided opportunities to study beta cell function through imaging zinc release from insulin secreting beta cells. Understanding the temporal secretory pattern of insulin and zinc corelease after a glucose challenge is essential for proper timing of administration of zinc sensing probes. Portal venous sampling is an essential part of pharmacological and nutritional studies in animal models. The purpose of this study was to compare two different percutaneous image-guided techniques: transhepatic ultrasound guided portal vein access and transsplenic fluoroscopy guided splenic vein access for ease of access, safety, and evaluation of temporal kinetics of insulin and zinc release into the venous effluent from the pancreas. Both techniques were safe, reproducible, and easy to perform. The mean time required to obtain desired catheter position for venous sampling was 15 minutes shorter using the transsplenic technique. A clear biphasic insulin release profile was observed in both techniques. Statistically higher insulin concentration but similar zinc release after a glucose challenge was observed from splenic vein samples, as compared to the ones from the portal vein. To our knowledge, this is the first report of percutaneous methods to assess zinc release kinetics from the porcine pancreas. PMID- 26273677 TI - Effect of Rosiglitazone and Insulin Combination Therapy on Inflammation Parameters and Adipocytokine Levels in Patients with Type 1 DM. AB - AIM: To investigate the efficacy of combined therapy of insulin and rosiglitazone on metabolic and inflammatory parameters, insulin sensitivity, and adipocytokine levels in patients with type 1 diabetes mellitus (type 1 DM). MATERIAL AND METHODS: A total of 61 adults with type 1 DM were randomly and prospectively assigned in open-label fashion to take insulin and rosiglitazone 4 mg/day (n = 30) or insulin alone (n = 31) for a period of 18 weeks while undergoing insulin therapy without acute metabolic complications. RESULTS: Combination therapy did not significantly improve metabolic and inflammatory parameters, insulin sensitivity, and adiponectin levels. While leptin and resistin levels decreased in both groups (group 1: resistin 6.96 +/- 3.06 to 4.99 +/- 2.64, P = 0.006; leptin 25.8 +/- 17.6 to 20.1 +/- 12.55, P = 0.006; group 2: resistin 7.16 +/- 2.30 to 5.57 +/- 2.48, P = 0.031; leptin 16.72 +/- 16.1 to 14.0 +/- 13.4, P = 0.007) Hgb and fibrinogen levels decreased only in group 1 (Hgb 13.72 +/- 1.98 to 13.16 +/- 1.98, P = 0.015, and fibrinogen 4.00 +/- 1.08 to 3.46 +/- 0.90, P = 0.002). Patients in both groups showed weight gain and the incidence of hypoglycemia was not lower. DISCUSSION: The diverse favorable effects of TZDs were not fully experienced in patients with type 1 DM. These results are suggesting that insulin sensitizing and anti-inflammatory characteristics of TZDs were likely to be more pronounced in patients who were not totally devoid of endogenous insulin secretion. PMID- 26273678 TI - Adipose Tissues Characteristics of Normal, Obesity, and Type 2 Diabetes in Uygurs Population. AB - Our results showed that, at the same BMI level, Uygurs have greater WHR values, abdominal visceral fat content, and diabetes risks than Kazaks. In addition, values of HDL-C in Uygur subjects were lower than those in Kazak subjects, and values of creatinine, uric acid, diastolic blood pressure, blood glucose, and fructosamine in Uygur male subjects were lower than those in Kazak male subjects. In contrast, systolic blood pressure values in Uygur subjects were greater than those in Kazak subjects, and blood glucose values were greater in Uygur female subjects than in Kazak female subjects. Additionally, in Uygurs, visceral adipose tissue expression levels of TBX1 and TCF21 were greater in obesity group than in normal and T2DM groups and lower in T2DM group than in normal group (P < 0.01). The visceral adipose tissue expression levels of APN in normal group was greater than those in obesity and T2DM groups, and visceral adipose tissue expression levels of TNF-alpha and MCP-1 in normal group were lower than those in obesity and T2DM groups (P < 0.01). In conclusion, T2DM in Uygurs was mainly associated with not only distribution of adipose tissue in body, but also change in metabolic activity and adipocytokines secretion of adipose tissue. PMID- 26273679 TI - MicroRNA-223 Expression is Upregulated in Insulin Resistant Human Adipose Tissue. AB - MicroRNAs (miRNAs) are short noncoding RNAs involved in posttranscriptional regulation of gene expression and influence many cellular functions including glucose and lipid metabolism. We previously reported that adipose tissue (AT) from women with polycystic ovary syndrome (PCOS) or controls with insulin resistance (IR) revealed a differentially expressed microRNA (miRNA) profile, including upregulated miR-93 in PCOS patients and in non-PCOS women with IR. Overexpressed miR-93 directly inhibited glucose transporter isoform 4 (GLUT4) expression, thereby influencing glucose metabolism. We have now studied the role of miR-223, which is also abnormally expressed in the AT of IR subjects. Our data indicates that miR-223 is significantly overexpressed in the AT of IR women, regardless of whether they had PCOS or not. miR-223 expression in AT was positively correlated with HOMA-IR. Unlike what is reported in cardiomyocytes, overexpression of miR-223 in human differentiated adipocytes was associated with a reduction in GLUT4 protein content and insulin-stimulated glucose uptake. In addition, our data suggests miR-223 regulates GLUT4 expression by direct binding to its 3' untranslated region (3'UTR). In conclusion, in AT miR-223 is an IR related miRNA that may serve as a potential therapeutic target for the treatment of IR-related disorders. PMID- 26273680 TI - Inflammatory Cytokine Profile Associated with Metabolic Syndrome in Adult Patients with Type 1 Diabetes. AB - OBJECTIVE: To compare the serum concentration of IL-6, IL-10, TNF, IL-8, resistin, and adiponectin in type 1 diabetic patients with and without metabolic syndrome and to determine the cut-off point of the estimated glucose disposal rate that accurately differentiated these groups. DESIGN: We conducted a cross sectional evaluation of all patients in our type 1 diabetes clinic from January 2012 to January 2013. Patients were considered to have metabolic syndrome when they fulfilled the joint statement criteria and were evaluated for clinical, biochemical, and immunological features. METHODS: We determined serum IL-6, IL-8, IL-10, and TNF with flow cytometry and adiponectin and resistin concentrations with enzyme linked immunosorbent assay in patients with and without metabolic syndrome. We also compared estimated glucose disposal rate between groups. RESULTS: We tested 140 patients. Forty-four percent fulfilled the metabolic syndrome criteria (n = 61), 54% had central obesity, 30% had hypertriglyceridemia, 29% had hypoalphalipoproteinemia, and 19% had hypertension. We observed that resistin concentrations were higher in patients with MS. CONCLUSION: . We found a high prevalence of MS in Mexican patients with T1D. The increased level of resistin may be related to the increased fat mass and could be involved in the development of insulin resistance. PMID- 26273681 TI - Research Progress on Regulatory T Cells in Acute Kidney Injury. AB - Immune inflammation is crucial in mediating acute kidney injury (AKI). Immune cells of both the innate and adaptive immune systems substantially contribute to overall renal damage in AKI. Regulatory T cells (Tregs) are key regulator of immunological function and have been demonstrated to ameliorate injury in several murine experimental models of renal inflammation. Recent studies have illuminated the renal-protective function of Tregs in AKI. Tregs appear to exert beneficial effects in both the acute injury phase and the recovery phase of AKI. Additionally, Tregs-based immunotherapy may represent a promising approach to ameliorate AKI and promote recovery from AKI. This review will highlight the recent insights into the role of Tregs and their therapeutic potential in AKI. PMID- 26273682 TI - Polyclonal Recipient nTregs Are Superior to Donor or Third-Party Tregs in the Induction of Transplantation Tolerance. AB - Induction of donor-specific tolerance is still considered as the "Holy Grail" in transplantation medicine. The mixed chimerism approach is virtually the only tolerance approach that was successfully translated into the clinical setting. We have previously reported successful induction of chimerism and tolerance using cell therapy with recipient T regulatory cells (Tregs) to avoid cytotoxic recipient treatment. Treg therapy is limited by the availability of cells as large-scale expansion is time-consuming and associated with the risk of contamination with effector cells. Using a costimulation-blockade based bone marrow (BM) transplantation (BMT) model with Treg therapy instead of cytoreductive recipient treatment we aimed to determine the most potent Treg population for clinical translation. Here we show that CD4(+)CD25(+) in vitro activated nTregs are superior to TGFbeta induced iTregs in promoting the induction of chimerism and tolerance. Therapy with nTregs (but not iTregs) led to multilineage chimerism and donor-specific tolerance in mice receiving as few as 0.5 * 10(6) cells. Moreover, we show that only recipient Tregs, but not donor or third-party Tregs, had a beneficial effect on BM engraftment at the tested doses. Thus, recipient-type nTregs significantly improve chimerism and tolerance and might be the most potent Treg population for translation into the clinical setting. PMID- 26273683 TI - BPI-ANCA Provides Additional Clinical Information to Anti-Pseudomonas Serology: Results from a Cohort of 117 Swedish Cystic Fibrosis Patients. AB - Patients with cystic fibrosis (CF) colonized with Pseudomonas aeruginosa (P. aeruginosa) have worse prognosis compared with patients who are not. BPI-ANCA is an anti-neutrophil cytoplasmic antibody against BPI (bactericidal/permeability increasing protein) correlating with P. aeruginosa colonization and adverse long time prognosis. Whether it provides additional information as compared to standard anti-P. aeruginosa serology tests is not known. 117 nontransplanted CF patients at the CF centre in Lund, Sweden, were followed prospectively for ten years. Bacterial colonisation was classified according to the Leeds criteria. IgA BPI-ANCA was compared with assays for antibodies against alkaline protease (AP), Elastase (ELA), and Exotoxin A (ExoA). Lung function and patient outcome, alive, lung transplanted, or dead, were registered. BPI-ANCA showed the highest correlation with lung function impairment with an r-value of 0.44. Forty-eight of the 117 patients were chronically colonized with P. aeruginosa. Twenty of these patients experienced an adverse outcome. Receiver operator curve (ROC) analysis revealed that this could be predicted by BPI-ANCA (AUC = 0.77), (p = 0.002) to a better degree compared with serology tests. BPI-ANCA correlates better with lung function impairment and long time prognosis than anti-P. aeruginosa serology and has similar ability to identify patients with chronic P. aeruginosa. PMID- 26273684 TI - Aggregation of MBP in chronic demyelination. AB - OBJECTIVES: Misfolding of key disease proteins to an insoluble state is associated with most neurodegenerative conditions, such as prion, Parkinson, and Alzheimer's diseases. In this work, and by studying animal models of multiple sclerosis, we asked whether this is also the case for myelin basic protein (MBP) in the late and neurodegenerative phases of demyelinating diseases. METHODS: To this effect, we tested whether MBP, an essential myelin component, present prion like properties in animal models of MS, as is the case for Cuprizone-induced chronic demyelination or chronic phases of Experimental Autoimmune Encephalomyelitis (EAE). RESULTS: We show here that while total levels of MBP were not reduced following extensive demyelination, part of these molecules accumulated thereafter as aggregates inside oligodendrocytes or around neuronal cells. In chronic EAE, MBP precipitated concomitantly with Tau, a marker of diverse neurodegenerative conditions, including MS. Most important, analysis of fractions from Triton X-100 floatation gradients suggest that the lipid composition of brain membranes in chronic EAE differs significantly from that of naive mice, an effect which may relate to oxidative insults and subsequently prevent the appropriate insertion and compaction of new MBP in the myelin sheath, thereby causing its misfolding and aggregation. INTERPRETATION: Prion-like aggregation of MBP following chronic demyelination may result from an aberrant lipid composition accompanying this pathological status. Such aggregation of MBP may contribute to neuronal damage that occurs in the progressive phase of MS. PMID- 26273685 TI - Identification of a neurovascular signaling pathway regulating seizures in mice. AB - OBJECTIVE: A growing body of evidence suggests that increased blood-brain barrier (BBB) permeability can contribute to the development of seizures. The protease tissue plasminogen activator (tPA) has been shown to promote BBB permeability and susceptibility to seizures. In this study, we examined the pathway regulated by tPA in seizures. METHODS: An experimental model of kainate-induced seizures was used in genetically modified mice, including mice deficient in tPA (tPA (-/-) ), its inhibitor neuroserpin (Nsp (-/-) ), or both (Nsp:tPA (-/-) ), and in mice conditionally deficient in the platelet-derived growth factor receptor alpha (PDGFRalpha). RESULTS: Compared to wild-type (WT) mice, Nsp (-/-) mice have significantly reduced latency to seizure onset and generalization; whereas tPA ( /-) mice have the opposite phenotype, as do Nsp:tPA (-/-) mice. Furthermore, interventions that maintain BBB integrity delay seizure propagation, whereas osmotic disruption of the BBB in seizure-resistant tPA (-/-) mice dramatically reduces the time to seizure onset and accelerates seizure progression. The phenotypic differences in seizure progression between WT, tPA (-/-) , and Nsp (-/ ) mice are also observed in electroencephalogram recordings in vivo, but absent in ex vivo electrophysiological recordings where regulation of the BBB is no longer necessary to maintain the extracellular environment. Finally, we demonstrate that these effects on seizure progression are mediated through signaling by PDGFRalpha on perivascular astrocytes. INTERPRETATION: Together, these data identify a specific molecular pathway involving tPA-mediated PDGFRalpha signaling in perivascular astrocytes that regulates seizure progression through control of the BBB. Inhibition of PDGFRalpha signaling and maintenance of BBB integrity might therefore offer a novel clinical approach for managing seizures. PMID- 26273686 TI - A randomized controlled trial of exercise in spinal and bulbar muscular atrophy. AB - OBJECTIVE: To determine the safety and efficacy of a home-based functional exercise program in spinal and bulbar muscular atrophy (SBMA). METHODS: Subjects were randomly assigned to participate in 12 weeks of either functional exercises (intervention) or a stretching program (control) at the National Institutes of Health in Bethesda, MD. A total of 54 subjects enrolled, and 50 completed the study with 24 in the functional exercise group and 26 in the stretching control group. The primary outcome measure was the Adult Myopathy Assessment Tool (AMAT) total score, and secondary measures included total activity by accelerometry, muscle strength, balance, timed up and go, sit-to-stand test, health-related quality of life, creatine kinase, and insulin-like growth factor-1. RESULTS: Functional exercise was well tolerated but did not lead to significant group differences in the primary outcome measure or any of the secondary measures. The functional exercise did not produce significantly more adverse events than stretching, and was not perceived to be difficult. To determine whether a subset of the subjects may have benefited, we divided them into high and low functioning based on baseline AMAT scores and performed a post hoc subgroup analysis. Low functioning individuals receiving the intervention increased AMAT functional subscale scores compared to the control group. INTERPRETATION: Although these trial results indicate that functional exercise had no significant effect on total AMAT scores or on mobility, strength, balance, and quality of life, post hoc findings indicate that low-functioning men with SBMA may respond better to functional exercises, and this warrants further investigation with appropriate exercise intensity. PMID- 26273687 TI - CSF neurofilament light chain reflects corticospinal tract degeneration in ALS. AB - OBJECTIVE: Diffusion tensor imaging (DTI) is sensitive to white matter tract pathology. A core signature involving the corticospinal tracts (CSTs) has been identified in amyotrophic lateral sclerosis (ALS). Raised neurofilament light chain protein (NfL) in cerebrospinal fluid (CSF) is thought to reflect axonal damage in a range of neurological disorders. The relationship between these two measures was explored. METHODS: CSF and serum NfL concentrations and DTI acquired at 3 Tesla on the same day were obtained from ALS patients (n = 25 CSF, 40 serum) and healthy, age-similar controls (n = 17 CSF, 25 serum). Within-group correlations between NfL and DTI measures of microstructural integrity in major white matter tracts (CSTs, superior longitudinal fasciculi [SLF], and corpus callosum) were performed using tract-based spatial statistics. RESULTS: NfL levels were higher in patients compared to controls. CSF levels correlated with clinical upper motor neuron burden and rate of disease progression. Higher NfL levels were significantly associated with lower DTI fractional anisotropy and increased radial diffusivity in the CSTs of ALS patients, but not in controls. INTERPRETATION: Elevated CSF and serum NfL is, in part, a result of CST degeneration in ALS. This highlights the wider potential for combining neurochemical and neuroimaging-based biomarkers in neurological disease. PMID- 26273688 TI - A systems-level "misunderstanding": the plasma metabolome in Huntington's disease. AB - OBJECTIVE: Huntington's disease (HD) is a rare neurodegenerative disease caused by the expansion of an N-terminal repeat in the huntingtin protein. The protein is expressed in all cells in the body; hence, peripheral tissues, such as blood, may recapitulate processes in the brain. The plasma metabolome may provide a window into active processes that influence brain health and a unique opportunity to noninvasively identify processes that may contribute to neurodegeneration. Alterations in metabolic pathways in brain have been shown to profoundly impact HD. Therefore, identification and quantification of critical metabolomic perturbations could provide novel biomarkers for disease onset and disease progression. METHODS: We analyzed the plasma metabolomic profiles from 52 premanifest (PHD), 102 early symptomatic HD, and 140 healthy controls (NC) using liquid chromatography coupled with a highly sensitive electrochemical detection platform. RESULTS: Alterations in tryptophan, tyrosine, purine, and antioxidant pathways were identified, including many related to energetic and oxidative stress and derived from the gut microbiome. Multivariate statistical modeling demonstrated mutually distinct metabolomic profiles, suggesting that the processes that determine onset were likely distinct from those that determine progression. Gut microbiome-derived metabolites particularly differentiated the PHD metabolome, while the symptomatic HD metabolome was increasingly influenced by metabolites that may reflect mutant huntingtin toxicity and neurodegeneration. INTERPRETATION: Understanding the complex changes in the delicate balance of the metabolome and the gut microbiome in HD, and how they relate to disease onset, progression, and phenotypic variability in HD are critical questions for future research. PMID- 26273689 TI - Low neural exosomal levels of cellular survival factors in Alzheimer's disease. AB - Transcription factors that mediate neuronal defenses against diverse stresses were quantified in plasma neural-derived exosomes of Alzheimer's disease or frontotemporal dementia patients and matched controls. Exosomal levels of low density lipoprotein receptor-related protein 6, heat-shock factor-1, and repressor element 1-silencing transcription factor all were significantly lower in Alzheimer's disease patients than controls (P < 0.0001). In frontotemporal dementia, the only significant difference was higher levels of repressor element 1-silencing transcription factor than in controls. Exosomal transcription factors were diminished 2-10 years before clinical diagnosis of Alzheimer's disease. Low exosomal levels of survival proteins may explain decreased neuronal resistance to Alzheimer's disease neurotoxic proteins. PMID- 26273690 TI - Interferon-alpha and the calcifying microangiopathy in Aicardi-Goutieres syndrome. AB - Aicardi-Goutieres syndrome is a leukoencephalopathy with calcifications and increased cerebrospinal fluid interferon-alpha. The relation between interferon alpha and brain pathology is poorly understood. We report a patient with mutations in the disease-associated gene SAMHD1. Neuropathology showed an extensive microangiopathy with calcifications consistently associate with blood vessels. In an in vitro model of the microangiopathy, interferon-alpha enhanced vascular smooth muscle cell-derived calcifications. The noninfarcted white matter harbored apoptotic oligodendrocytes and increased numbers of oligodendrocyte progenitors. These findings better define the white matter pathology and provide evidence that interferon-alpha plays a direct pathogenetic role in the calcifying angiopathy typical of this disease. PMID- 26273691 TI - Rapidly progressive intracranial artery stenosis in primary antiphospholipid syndrome. AB - Antiphospholipid antibody syndrome (APS) is usually a disease of young adults. In elderly stroke patients APS was not associated with progressive intracerebral stenosis in the past. Here, we report a 65-year-old patient who presented with recurrent ischemic strokes associated with progressive stenosis of the right middle cerebral artery. Antiphospholipid antibodies were detected and treatment with plasma exchange, tapered steroids, and anticoagulants was successful. This case demonstrates that APS should be considered also in elderly stroke patients. This is of particular relevance since APS confers a significant risk to angioplasty and stenting procedures which therefore should be avoided in APS. PMID- 26273692 TI - Comment on: A novel dysferlin-mutant pseudoexon bypassed with antisense oligonucleotides. PMID- 26273694 TI - Editorial overview: The assessment, etiology, and treatment of unipolar depression. PMID- 26273697 TI - Dynamic and Structural Performances of a New Sailcraft Concept for Interplanetary Missions. AB - Typical square solar-sail design is characterised by a central hub with four quadrant sails, conferring to the spacecraft the classical X-configuration. One of the critical aspects related to this architecture is due to the large deformations of both membrane and booms, which leads to a reduction of the performance of the sailcraft in terms of thrust efficiency. As a consequence, stiffer sail architecture would be desirable, taking into account that the rigidity of the system strongly affects the orbital dynamics. In this paper, we propose a new solar-sail architecture, which is more rigid than the classical X configuration. Among the main pros and cons that the proposed configuration presents, this paper aims to show the general concept, investigating the performances from the perspectives of both structural response and attitude control. Membrane deformations, structural offset, and sail vibration frequencies are determined through finite element method, adopting a variable pretensioning scheme. In order to evaluate the manoeuvring performances of this new solar-sail concept, a 35-degree manoeuvre is studied using a feedforward and feedback controller. PMID- 26273696 TI - Acute Toxicity and Dermal and Eye Irritation of the Aqueous and Hydroalcoholic Extracts of the Seeds of "Zapote" Pouteria mammosa (L.) Cronquist. AB - The common use of Pouteria mammosa (L.) Cronquist, "Mamey or Zapote," in food and ethnobotanic medicine shows its low or absent toxicity as fruit extracts prepared from seeds. However, it is essential to conduct security trials to scientifically support their use in drug therapy. This study evaluated the aqueous and hydroalcoholic extract (25%) Acute Oral Toxicity, obtained from the seeds of P. mammosa, in Sprague Dawley rats and dermal and eye irritability in New Zealand rabbits. The 404 and 405 acute dermal and eye irritation/corrosion guidelines were used, as well as the 423 Acute Oral Toxicity guideline, Acute Toxic Class Method of the Organization for Economic Cooperation and Development (OECD). The aqueous extract was located in the following category: not classified as toxic (CTA 5), while hydroalcoholic extract at 25% was classified as dangerous (CTA 4). Both extracts can be used without side reaction that irritates the skin which permitted classification as potentially not irritant. P. mammosa in the two extracts caused mild and reversible eye irritation, and it was classified as slightly irritating. PMID- 26273695 TI - Functional and structural features of cholangiocytes in health and disease. AB - Cholangiocytes are the epithelial cells that line the bile ducts. Along the biliary tree, two different kinds of cholangiocytes exist; small and large cholangiocytes. Each type has important differences in their biological role in physiological and pathological conditions. In response to injury, cholangiocytes become reactive and acquire a neuroendocrine-like phenotype with the secretion of a number of peptides. These molecules act in an autocrine/paracrine fashion to modulate cholangiocyte biology and determine the evolution of biliary damage. The failure of such mechanisms is believed to influence the progression of cholangiopathies, a group of diseases that selectively target biliary cells. Therefore, the understanding of mechanisms regulating cholangiocyte response to injury is expected to foster the development of new therapeutic options to treat biliary diseases. In the present review, we will discuss the most recent findings in the mechanisms driving cholangiocyte adaptation to damage, with particular emphasis on molecular pathways that are susceptible of therapeutic intervention. Morphogenic pathways (Hippo, Notch, Hedgehog), which have been recently shown to regulate biliary ontogenesis and response to injury, will also be reviewed. In addition, the results of ongoing clinical trials evaluating new drugs for the treatment of cholangiopathies will be discussed. PMID- 26273698 TI - Coapplication of Chicken Litter Biochar and Urea Only to Improve Nutrients Use Efficiency and Yield of Oryza sativa L. Cultivation on a Tropical Acid Soil. AB - The excessive use of nitrogen (N) fertilizers in sustaining high rice yields due to N dynamics in tropical acid soils not only is economically unsustainable but also causes environmental pollution. The objective of this study was to coapply biochar and urea to improve soil chemical properties and productivity of rice. Biochar (5 t ha(-1)) and different rates of urea (100%, 75%, 50%, 25%, and 0% of recommended N application) were evaluated in both pot and field trials. Selected soil chemical properties, rice plants growth variables, nutrient use efficiency, and yield were determined using standard procedures. Coapplication of biochar with 100% and 75% urea recommendation rates significantly increased nutrients availability (especially P and K) and their use efficiency in both pot and field trials. These treatments also significantly increased rice growth variables and grain yield. Coapplication of biochar and urea application at 75% of the recommended rate can be used to improve soil chemical properties and productivity and reduce urea use by 25%. PMID- 26273699 TI - Thrombospondin-1 Modulates Actin Filament Remodeling and Cell Motility in Mouse Mammary Tumor cells in Vitro. AB - It is well established that the secretion of thrombospondin-1 (TSP-1) by activated stromal cells and its accumulation in the tumor microenvironment during dysplasia inhibits primary tumor growth through inhibition of angiogenesis. This inhibitory function of TSP-1 is actuated either by inhibiting MMP9 activation and the release of VEGF from extracellular matrix or by an interaction with CD36 on the surface of endothelial cells resulting in an increase in apoptosis. In contrast, several published articles have also shown that as tumor cells become more invasive and enter the early stage of carcinoma, they up-regulate TSP-1 expression, which may promote invasion and migration. In our in vivo studies using the polyoma middle T antigen (PyT) transgenic mouse model of breast cancer, we observed that the absence of TSP-1 significantly increased the growth of primary tumors, but delayed metastasis to the lungs. In this study, we propose a mechanism for the promigratory function of TSP-1 in mouse mammary tumor cells in vitro. We demonstrate the correlations between expression of TSP-1 and its receptor integrin alpha3beta1, which is considered a promigratory protein in cancer cells. In addition we propose that binding of TSP-1 to integrin alpha3beta1 is important for mediating actin filament polymerization and therefore, cell motility. These findings can help explain the dual functionality of TSP-1 in cancer progression. PMID- 26273701 TI - Comparison of Simulated Workplace Protection Factors Offered by N95 and P100 Filtering Facepiece and Elastomeric Half-Mask Respirators against Particles of 10 to 400 nm. AB - This study compared the simulated workplace protection factors (SWPFs) between NIOSH-approved N95 respirators and P100 respirators, including two models of filtering facepiece respirator (FFR) and two models of elastomeric half-mask respirator (EHR), against sodium chloride particles (NaCl) in a range of 10 to 400 nm. Twenty-five human test subjects performed modified OSHA fit test exercises in a controlled laboratory environment with the N95 respirators (two FFR models and two EHR models) and the P100 respirators (two FFRs and two EHRs). Two Scanning Mobility Particle Sizers (SMPS) were used to measure aerosol concentrations (in the 10-400 nm size range) inside (Cin) and outside (Cout) of the respirator, simultaneously. SWPF was calculated as the ratio of Cout to Cin. The SWPF values obtained from the N95 respirators were then compared to those of the P100 respirators. SWPFs were found to be significantly different (P<0.05) between N95 and P100 class respirators. The 10th, 25th, 50th, 75th and 90th percentiles of the SWPFs for the N95 respirators were much lower than those for the P100 models. The N95 respirators had 5th percentiles of the SWPFs > 10. In contrast, the P100 class was able to generate 5th percentiles SWPFs > 100. No significant difference was found in the SWPFs when tested against nano-size (10 to 100 nm) and large-size (100 to 400 nm) particles. Overall, the findings suggest that the two FFRs and two EHRs with P100 class filters provide better performance than those with N95 filters against particles from 10 to 400 nm, supporting current OSHA and NIOSH recommendations. PMID- 26273700 TI - Interleukin-1 in cardiac injury, repair, and remodeling: pathophysiologic and translational concepts. AB - In the infarcted myocardium, necrotic cardiomyocytes release danger signals activating an intense inflammatory reaction that serves to clear the wound from dead cells and matrix debris, but may also extend injury. A growing body of evidence suggests an important role for members of the Interleukin (IL)-1 family in injury, repair and remodeling of the infarcted heart. This review manuscript discusses the pathophysiologic functions of IL-1 in the infarcted and remodeling myocardium and its potential role as a therapeutic target in patients with myocardial infarction. Dead cardiomyocytes release IL-1alpha that may function as a crucial alarmin triggering the post-infarction inflammatory reaction. IL-1beta is markedly upregulated in the infarcted myocardium; activation of the inflammasome in both cardiomyocytes and interstitial cells results in release of bioactive IL-1beta in the infarcted area. Binding of IL-1 to the type 1 receptor triggers an inflammatory cascade, inducing recruitment of pro-inflammatory leukocytes and stimulating a matrix-degrading program in fibroblasts, while delaying myofibroblast conversion. IL-1 mediates dilative remodeling following infarction and may play a role in the pathogenesis of post-infarction heart failure. As the wound is cleared from dead cells and matrix debris, endogenous inhibitory signals suppress the IL-1 response resulting in repression of inflammation and resolution of the inflammatory infiltrate. Other members of the IL-1 family (such as IL-18 and IL-33) are also implicated in regulation of the inflammatory and reparative response following myocardial infarction. IL-18 may participate in pro-inflammatory signaling, whereas IL-33 may exert cytoprotective effects. Early clinical trials suggest that IL-1 blockade may be a promising therapeutic strategy for patients with myocardial infarction. PMID- 26273703 TI - Functional hierarchy of redundant actin assembly factors revealed by fine-grained registration of intrinsic image fluctuations. AB - Highly redundant pathways often contain components whose functions are difficult to decipher from the responses induced by genetic or molecular perturbations. Here, we present a statistical approach that samples and registers events observed in images of intrinsic fluctuations in unperturbed cells to establish the functional hierarchy of events in systems with redundant pathways. We apply this approach to study the recruitment of actin assembly factors involved in the protrusion of the cell membrane. We find that the formin mDia1, along with nascent adhesion components, is recruited to the leading edge of the cell before protrusion onset, initiating linear growth of the lamellipodial network. Recruitment of Arp2/3, VASP, cofilin, and the formin mDia2 then promotes sustained exponential growth of the network. Experiments changing membrane tension suggest that Arp2/3 recruitment is mechano-responsive. These results indicate that cells adjust the overlapping contributions of multiple factors to actin filament assembly during protrusion on a ten-second timescale and in response to mechanical cues. PMID- 26273702 TI - Maternal post-absorptive leucine kinetics during late pregnancy in US women with HIV taking antiretroviral therapy: a cross-sectional pilot study. AB - BACKGROUND: Despite the success of combination antiretroviral therapy (cART) for the prevention of mother to child transmission of HIV, infants exposed to cART in utero frequently are born smaller and have mild cardiac abnormalities. The mechanisms responsible for lower birth weight and cardiac abnormalities in children exposed to cART are unclear but could be related to dysregulation of maternal amino acid metabolism during pregnancy. Previous data in HIV(-) women have shown a relationship between abnormal maternal protein metabolism during pregnancy and low infant birth weight and animal data demonstrate a relationship between altered maternal protein metabolism and increased risk for offspring cardiovascular abnormalities. OBJECTIVE: The objectives of this study were to: characterize post-absorptive maternal leucine kinetics during late pregnancy andexamine the relationships between maternal leucine kinetics and offspring birth weight and cardiac function. DESIGN: Post-absorptive maternal leucine kinetics (evaluated by using stable isotope tracer methodology) in 16 HIV(+) women receiving cART and 14 HIV(-) US women during the 3rd trimester of pregnancy were compared. Relationships between post-absorptive maternal leucine kinetics, cardiac function (echocardiography) and birth weight were statistically examined. RESULTS: Maternal plasma leucine concentration (HIV(-): 82.8 +/- 10.7 vs. HIV(+): 72.3 +/- 13.5 MUM, p=0.06) and leucine oxidation rate (HIV(-): 6.1 +/- 1.6 vs. HIV(+): 4.9 +/- 1.8 MUmol/kgBW/min, p=0.03) were lower in HIV+ women compared to controls. Total leucine turnover rate, non-oxidative leucine disposal rate and post-absorptive maternal glucose and palmitate kinetics did not differ between groups. Left ventricular fractional shortening tended to be lower in children born to HIV(+) compared to controls (HIV(-): 42 +/- 1 vs. HIV+: 36 +/- 5 %, p=0.08) and associated with lower maternal plasma leucine concentration (r= 0.43, p=0.08). CONCLUSIONS: Preliminary results indicate that post-absorptive maternal leucine metabolism during late pregnancy is mildly altered in HIV+ US women taking cART. The clinical significance of maternal leucine metabolism on adverse infant outcomes is unclear and should be further explored in more expansive studies. PMID- 26273704 TI - An ultrahigh-contrast and broadband on-chip refractive index sensor based on a surface-plasmon-polariton interferometer. AB - Using a double-slit structure fabricated on a gold film or a subwavelength (300 nm) plasmonic waveguide, high-contrast and broadband plasmonic sensors based on the interference of surface plasmon polaritons (SPPs) are experimentally demonstrated on chips. By adjusting the focused spot position of the p-polarized incident light on the double-slit structure to compensate for the propagation loss of the SPPs, the interfering SPPs from the two slits have nearly equal intensities. As a result, nearly completely destructive interference can be experimentally achieved in a broad bandwidth (>200 nm), revealing the robust design and fabrication of the double-slit structure. More importantly, a high sensing figure of merit (FOM*) of >1 * 10(4) RIU(-1) (refractive index unit), which is much greater than the previous experimental results, is obtained at the destructive wavelength because of a high contrast ratio (C = 0.96). The high contrast and broadband on-chip sensor fabricated on the subwavelength plasmonic waveguide may find important applications in the real-time sensing of particles and molecules. PMID- 26273705 TI - Correction: Cold shock induces apoptosis of dorsal root ganglion neurons plated on infrared windows. AB - Correction for 'Cold shock induces apoptosis of dorsal root ganglion neurons plated on infrared windows' by Ebrahim Aboualizadeh et al., Analyst, 2015, 140, 4046-4056. PMID- 26273706 TI - A poly(ADP-ribose) polymerase-1 activity assay based on the FRET between a cationic conjugated polymer and supercharged green fluorescent protein. AB - A label-free and convenient strategy for PARP-1 activity assay and inhibitors assessment has been developed based on the fluorescence resonance energy transfer (FRET) between a cationic conjugated polymer (CCP) and supercharged green fluorescent protein (scGFP). PMID- 26273707 TI - Enantio- and diastereoselective synthesis of gamma-amino alcohols. AB - The gamma-amino alcohol structural motif is often encountered in drugs and natural products. We developed two complementary catalytic diastereoselective methods for the synthesis of N-PMP-protected gamma-amino alcohols from the corresponding ketones. The anti-products were obtained through Ir-catalyzed asymmetric transfer hydrogenation, the syn-products via Rh-catalyzed asymmetric hydrogenation. PMID- 26273708 TI - Two site genetic incorporation of varying length polyethylene glycol into the backbone of one peptide. AB - Polyethylene glycol (PEG) of different lengths was genetically incorporated into the backbone of a polypeptide using stop-anticodon and frameshift anticodon containing tRNAs, which were acylated with PEG-containing amino acids. PMID- 26273709 TI - Halomethyl-cobalt(bis-acetylacetonate) for the controlled synthesis of functional polymers. AB - Novel organocobalt complexes featuring weak C-CoL2 bonds (L = acetylacetonate) are prepared and used as sources of halomethyl radicals. They permit the precision synthesis of alpha-halide functionalized and telechelic polymers in organic media or in water. Substitution of halide by azide allows derivatization of polymers using the CuAAC click reaction. PMID- 26273711 TI - Switzerland ranks happiest country. PMID- 26273712 TI - The definition of public health - where to shift the focus: prevention or population? PMID- 26273713 TI - [Digitalis therapy associated with increased risk of death]. PMID- 26273714 TI - Biomedical research: Drug hunters wanted. PMID- 26273715 TI - Antibiotic administration in the critically ill - in need of intensive care! PMID- 26273716 TI - Erratum. Computational insight in the role of fusogenic lipopeptides at the onset of liposome fusion. AB - We performed an extensive computational study to obtain insight in the molecular mechanisms that take place prior to membrane fusion. We focused on membrane anchored hybrid macromolecules (lipid-polymer-oligopeptide) that mimic biological SNARE proteins in terms of liposome fusion characteristics [H. Robson Marsden et al., 2009]; efficient micro-second simulation was enabled by combining validated MARTINI force fields for the molecular building blocks in coarse-grained molecular dynamics (CGMD). We find that individual peptide domains in the hybrid macromolecules bind and partially integrate parallel to the membrane surface, in agreement with experimental findings. By varying several experimental design parameters, we observe that peptide domains remain in the solvent phase only in two cases: (1) for solitary lipopeptides (low concentration), below a threshold area per lipid in the membrane, and (2) when the lipopeptide concentration is high enough for the peptide domains to self-assemble into tetrameric homo complexes. The peptide-membrane binding is not affected by solvent-induced peptide unfolding, which we mimicked by relaxing the usual MARTINI helix constraints. Remarkably, in this case, a reverse transition to a helical secondary structure is observed after binding, highlighting the role of the membrane as a template (partitioning-folding coupling). Our findings undermine the current view of the initial stages towards fusion, in which membranes are thought to be kept in close apposition via dimerization of individual complementary peptides in the solvent phase. Although we did not study actual fusion, our simulations show that the formation of homomers, which is suppressed in experimental peptide pair design and therefore believed to be insignificant for fusion, by peptides anchored to the same membrane does play a key role in this locking mechanism and potentially also in membrane destabilization that precedes fusion. PMID- 26273717 TI - Intensive blood pressure reduction in acute intracerebral hemorrhage: A meta analysis. PMID- 26273718 TI - Author response. PMID- 26273719 TI - Studies on Antibiotics Active against Resistant Bacteria. Total Synthesis of MRSA Active Tetarimycin A and Its Analogues. AB - Making use of the Hauser-Kraus annulation as a key step, the first total synthesis of tetarimycin A has been accomplished in a highly convergent and operationally simple manner. Preliminary SAR not only validated that tetarimycin A exhibited potent activity against MRSA and VRE at a low MIC value but also identified that the hydroxyl group at C-10 was essential for antibacterial activities. PMID- 26273721 TI - Subpicosecond Exciton Dynamics and Biexcitonic Feature in Colloidal CuInS2 Nanocrystals: Role of In-Cu Antisite Defects. AB - Charge carrier dynamics of multinary quantum dots like CuInS2 (CIS) nanocrystals (NCs) is not clearly understood, especially in ultrafast time scales. Herein we have synthesized colloidal CIS NCs that show defect-induced emission between donor (antisite) and acceptor (internal/surface) states as indicated from steady state and time-resolved photoluminescence (PL) measurements. Subpicosecond transient absorption (TA) spectra of CIS NCs reveal a gradient of electronic states that exists above the conduction band edge. The electron cooling rate has been determined to be ~0.1-0.15 eV/ps. The cascade of electron cooling dynamics was monitored after following the TA kinetics at different electronic states. Interestingly, the kinetics at the antisite state unveil a biexcitonic feature, which has been enlightened through a probe-induced biexciton mechanism. With progressively higher fluence (?N?), the biexciton binding energy increases, and the electron cooling to the antisite state considerably slows down. Extra energy released during Auger recombination of bi/multiexcitons are used to re-excite the electron to a further high energy level, resulting in longer electron cooling time to the antisite states. PMID- 26273720 TI - Dyadic dynamics of HIV risk among transgender women and their primary male sexual partners: the role of sexual agreement types and motivations. AB - Transgender women - individuals assigned a male sex at birth who identify as women, female, or on the male-to-female trans feminine spectrum - are at high risk of HIV worldwide. Prior research has suggested that transgender women more frequently engage in condomless sex with primary cisgender (i.e., non transgender) male partners compared with casual or paying partners, and that condomless sex in this context might be motivated by relationship dynamics such as trust and intimacy. The current study examined sexual agreement types and motivations as factors that shape HIV risk behaviors in a community sample of 191 transgender women and their cisgender primary male partners who completed a cross sectional survey. Overall, 40% of couples had monogamous, 15% open, and 45% discrepant sexual agreements (i.e., partners disagreed on their type of agreement). Actor-partner interdependence models were fit to examine the influence of sexual agreement type and motivations on extra-dyadic HIV risk (i.e., condomless sex with outside partners) and intra-dyadic HIV serodiscordant risk (i.e., condomless sex with serodiscordant primary partners). For male partners, extra-dyadic risk was associated with their own and their partners' sexual agreement motives, and male partners who engaged in extra-dyadic HIV risk had an increased odds of engaging in HIV serodiscordant intra-dyadic risk. Study findings support inclusion of the male partners of transgender women into HIV prevention efforts. Future research is warranted to explore the interpersonal and social contexts of sexual agreement types and motivations in relationships between transgender women and their male partners to develop interventions that meet their unique HIV prevention needs. PMID- 26273722 TI - A Rare Mutation in Patients With Resistance to Thyroid Hormone and Review of Therapeutic Strategies. AB - BACKGROUND: Resistance to thyroid hormone (RTH) is a rare syndrome characterized by elevated thyroid hormone (TH) along with nonsuppressed thyroid-stimulating hormone (TSH). The clinical symptoms can vary considerably, and no definite treatment has been established thus far. METHODS: A family with RTH harboring a TH receptor (THR)-beta gene mutation (A234T) is described, the therapeutic strategies for RTH are reviewed, and optimization of the treatment strategies was attempted. RESULTS: Gene sequencing revealed a point mutation (A234T) in the THR beta gene of the proposita, her elder brother and her mother. During the 20-month follow-up period, it was found that the proposita experienced apparently higher TSH level and normal TH level on taking antithyroid medication. However, on discontinuing the medication, her thyroid function returned to the baseline of elevated FT3, FT4 level along with inappropriately normal TSH. Thus far, there is no guideline regarding the treatment strategies for the RTH. Antithyroid drugs are effective for patients with thyrotoxic symptoms but pose an increased risk of thyrotroph hyperplasia. The efficacy and safety of D-T4 and bromocriptine still remains debatable, TRIAC may be the most promising drug, as it is effective and can reduce both TH and TSH level. However, L-T3 or L-T4 may be necessary for some RTH patients who exhibit massive goiter or hypothyroid symptoms. CONCLUSIONS: It is demonstrated in this article that the A234T mutation in the THR-beta gene can cause the RTH. Treatment of this condition is challenging, and individualized therapy is required because of the variable clinical features. PMID- 26273723 TI - Structure and Photochemistry of N-Salicylidene-p-carboxyaniline Isolated in Solid Argon. AB - Infrared matrix isolation spectroscopy and DFT/B3LYP/6-311++G(d,p) calculations have been used to characterize the conformational space of the enol-imine and keto-amine tautomers of N-salicylidene-p-carboxyaniline (SCA) in both their E and Z isomeric forms. Monomers of SCA were isolated in an argon matrix (15 K), which was shown to contain only the most stable conformer of the E-enol isomer of the compound. The matrix-isolated E-enol was then subjected to in situ UV irradiation (lambda = 335; 345 nm, provided by a laser/MOPO system, or lambda > 235 nm, provided by a Hg(Xe) broad-band source), and the photoinduced processes probed by infrared spectroscopy. Two photoreaction channels were observed, with a branching ratio of ~1:1, corresponding to E-enol -> Z-enol isomerization and E-enol -> E keto tautomerization. Both processes were found to be rather effective, with practically complete consumption of the reactant after broad-band irradiation by 1 min only. Identification among the photoproduced species of the Z-enol conformer that differs from the reactant only by E-to-Z isomerization suggests the initial photoproduction of this conformer, which subsequently decays into the lowest energy Z-enol conformer (also identified experimentally). The E-enol -> E keto tautomerization requires an excited state intramolecular proton transfer and twisting about the exocyclic CC bond of the molecule. These processes most probably take place sequentially. However, in the present study the Z-keto isomer, which should act as intermediate in this sequence of processes, could not be detected, most probably due to its short lifetime under the used experimental conditions. On the contrary, the detailed structural and vibrational characterization of the photoproduced E-keto form was successfully achieved. PMID- 26273724 TI - Who am I? Autobiographical retrieval improves access to self-concepts. AB - It is considered that an individual's current self-concept plays a crucial role in guiding the retrieval of autobiographical memory. Using a novel fluency paradigm, the present research examined whether or not the reverse is also true, that is, does memory retrieval influence the description of the conceptual self? Specifically, this study examined the effect of prior autobiographical reverie on the subsequent retrieval of stored self-concepts. Participants wrote a description of a personally relevant memory or a control topic (of no relevance to the self), following which they had 60 seconds to generate as many self defining statements as possible, each beginning with I am. Participants engaging in autobiographical retrieval generated significantly more statements than those in the control condition, suggesting that autobiographical retrieval increased access to self-concepts. Type of statement also varied according to group. Participants in the autobiographical memory condition were more likely to conceptualise themselves in relation to their psychological traits, and this was replicated in a second experiment conducted online. Findings support the idea that self and episodic memory are highly related constructs, and are discussed in relation to implications for individuals with autobiographical memory deficits. PMID- 26273725 TI - Hydnocarpin-Type Flavonolignans: Semisynthesis and Inhibitory Effects on Staphylococcus aureus Biofilm Formation. AB - A new, efficient, and general semisynthesis of hydnocarpin-type flavonolignans was developed and optimized, enabling gram-scale production of hydnocarpin D (2). Moreover, the syntheses of optically pure hydnocarpin isomers [(10R,11R) hydnocarpin (1a), (10R,11R)-hydnocarpin D (2a), and (10S,11S)-hydnocarpin D (2b)], as well as the synthesis of isohydnocarpin (8), were achieved for the first time utilizing this new method. The synthesis is based on the two-step transformation of the readily available flavonolignans from milk thistle (Silybum marianum), accessible by isolation from the commercial extract silymarin. The first step relies on the regioselective formylation of the C-3 hydroxy group of the dihydroflavonol-type precursor using the Vilsmeier-Haack reagent, followed by formic acid elimination by triethylamine in the second step. The synthesized compounds were effective inhibitors of Staphylococcus aureus biofilm formation, with (10S,11S)-hydnocarpin D (2b) being the most potent inhibitor. Furthermore, the effect of glucose on biofilm formation was tested, and glucose decreased the biofilm inhibitory activity of 2b. Moreover, 2b increased the susceptibility of Staph. aureus to enrofloxacin. PMID- 26273726 TI - Ultrasound Velocity Measurement in a Liquid Metal Electrode. AB - A growing number of electrochemical technologies depend on fluid flow, and often that fluid is opaque. Measuring the flow of an opaque fluid is inherently more difficult than measuring the flow of a transparent fluid, since optical methods are not applicable. Ultrasound can be used to measure the velocity of an opaque fluid, not only at isolated points, but at hundreds or thousands of points arrayed along lines, with good temporal resolution. When applied to a liquid metal electrode, ultrasound velocimetry involves additional challenges: high temperature, chemical activity, and electrical conductivity. Here we describe the experimental apparatus and methods that overcome these challenges and allow the measurement of flow in a liquid metal electrode, as it conducts current, at operating temperature. Temperature is regulated within +/-2 degrees C using a Proportional-Integral-Derivative (PID) controller that powers a custom-built furnace. Chemical activity is managed by choosing vessel materials carefully and enclosing the experimental setup in an argon-filled glovebox. Finally, unintended electrical paths are carefully prevented. An automated system logs control settings and experimental measurements, using hardware trigger signals to synchronize devices. This apparatus and these methods can produce measurements that are impossible with other techniques, and allow optimization and control of electrochemical technologies like liquid metal batteries. PMID- 26273727 TI - Sex of First Child and Breast Cancer Survival in Young Women. AB - Two studies have reported that young women with breast cancer face increased risk of early mortality if their first child was male rather than female. An immunological mechanism has been suggested. We sought to confirm these results in a larger, historical cohort study of 223 parous women who were aged <45 years at breast cancer diagnosis during 1983-1987. Subjects were identified through the Maine Cancer Registry. Follow-up data were obtained from hospitals, physicians, and death certificates. Reproductive history data were obtained from the next of kin of the deceased women, birth certificates, physicians, hospitals, and lastly, subjects. With a 7-year follow-up, multivariate modeling found a lower mortality risk in women with a male first child (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.32-0.81, log-rank comparison). The survival advantage remained for at least 13 years in women with a male firstborn. Thus, previous studies were not confirmed. Mortality risk in young women with breast cancer is not increased by having borne a male first child rather than a female first child. PMID- 26273728 TI - Different Dicer-like protein components required for intracellular and systemic antiviral silencing in Arabidopsis thaliana. AB - Eukaryotes employ RNA silencing as an innate defense system against invading viruses. Dicer proteins play the most crucial role in initiating this antiviral pathway as they recognize and process incoming viral nucleic acids into small interfering RNAs. Generally, 2 successive infection stages constitute viral infection in plants. First, the virus multiplies in initially infected cells or organs after viral transmission and then the virus subsequently spreads systemically through the vasculature to distal plant tissues or organs. Thus, antiviral silencing in plants must cope with both local and systemic invasion of viruses. In a recent study using 2 sets of different experiments, we clearly demonstrated the differential requirement for Dicer-like 4 (DCL4) and DCL2 proteins in the inhibition of intracellular and systemic infection by potato virus X in Arabidopsis thaliana. Taken together with the results of other studies, here we further discuss the functional specificity of DCL proteins in the antiviral silencing pathway. PMID- 26273729 TI - B2N2O4: Prediction of a Magnetic Ground State for a Light Main-Group Molecule. AB - Cyclobutanetetrone, (CO)4, has a triplet ground state. Here we predict, based on electronic structure calculations, that the B2N2O4 molecule also has a triplet ground state and is therefore paramagnetic; the structure is an analogue of (CO)4 in which the carbon ring is replaced by a (BN)2 ring. Similar to (CO)4, the triplet ground-state structure of B2N2O4 is also thermodynamically unstable. Besides analysis of the molecular orbitals, we found that the partial atomic charges are good indicators for predicting magnetic ground states. PMID- 26273730 TI - A longitudinal, population-based twin study of avoidant and obsessive-compulsive personality disorder traits from early to middle adulthood. AB - BACKGROUND: The phenotypic stability of avoidant personality disorder (AVPD) and obsessive-compulsive personality disorder (OCPD) has previously been found to be moderate. However, little is known about the longitudinal structure of genetic and environmental factors for these disorders separately and jointly, and to what extent genetic and environmental factors contribute to their stability. METHOD: AVPD and OCPD criteria were assessed using the Structured Interview for DSM-IV Personality in 2793 young adult twins (1385 pairs, 23 singletons) from the Norwegian Institute of Public Health Twin Panel at wave 1 and 2282 (986 pairs, 310 singletons) of these on average 10 years later at wave 2. Longitudinal biometric models were fitted to AVPD and OCPD traits. RESULTS: For twins who participated at both time-points, the number of endorsed sub-threshold criteria for both personality disorders (PDs) decreased 31% from wave 1 to wave 2. Phenotypic correlations between waves were 0.54 and 0.37 for AVPD and OCPD, respectively. The heritability estimates of the stable PD liabilities were 0.67 for AVPD and 0.53 for OCPD. The genetic correlations were 1.00 for AVPD and 0.72 for OCPD, while the unique environmental influences correlated 0.26 and 0.23, respectively. The correlation between the stable AVPD and OCPD liabilities was 0.39 of which 63% was attributable to genetic influences. Shared environmental factors did not significantly contribute to PD variance at either waves 1 or 2. CONCLUSION: Phenotypic stability was moderate for AVPD and OCPD traits, and genetic factors contributed more than unique environmental factors to the stability both within and across phenotypes. PMID- 26273731 TI - Observation of the Ciliary Movement of Choroid Plexus Epithelial Cells Ex Vivo. AB - The choroid plexus is located in the ventricular wall of the brain, the main function of which is believed to be production of cerebrospinal fluid. Choroid plexus epithelial cells (CPECs) covering the surface of choroid plexus tissue harbor multiple unique cilia, but most of the functions of these cilia remain to be investigated. To uncover the function of CPEC cilia with particular reference to their motility, an ex vivo observation system was developed to monitor ciliary motility during embryonic, perinatal and postnatal periods. The choroid plexus was dissected out of the brain ventricle and observed under a video-enhanced contrast microscope equipped with differential interference contrast optics. Under this condition, a simple and quantitative method was developed to analyze the motile profiles of CPEC cilia for several hours ex vivo. Next, the morphological changes of cilia during development were observed by scanning electron microscopy to elucidate the relationship between the morphological maturity of cilia and motility. Interestingly, this method could delineate changes in the number and length of cilia, which peaked at postnatal day (P) 2, while the beating frequency reached a maximum at P10, followed by abrupt cessation at P14. These techniques will enable elucidation of the functions of cilia in various tissues. While related techniques have been published in a previous report(1), the current study focuses on detailed techniques to observe the motility and morphology of CPEC cilia ex vivo. PMID- 26273732 TI - Reaction null-space filter: extracting reactionless synergies for optimal postural balance from motion capture data. AB - This paper introduces the notion of a reactionless synergy: a postural variation for a specific motion pattern/strategy, whereby the movements of the segments do not alter the force/moment balance at the feet. Given an optimal initial posture in terms of stability, a reactionless synergy can ensure optimality throughout the entire movement. Reactionless synergies are derived via a dynamical model wherein the feet are regarded to be unfixed. Though in contrast with the conventional fixed-feet models, this approach has the advantage of exhibiting the reactions at the feet explicitly. The dynamical model also facilitates a joint space decomposition scheme yielding two motion components: the reactionless synergy and an orthogonal complement responsible for the dynamical coupling between the feet and the support. Since the reactionless synergy provides the basis (a feedforward control component) for optimal balance control, it may play an important role when evaluating balance abnormalities or when assessing optimality in balance control. We show how to apply the proposed method for analysis of motion capture data obtained from three voluntary movement patterns in the sagittal plane: squat, sway, and forward bend. PMID- 26273733 TI - The Effect of Autologous Fat Graft with Different Surgical Repair Methods on Nerve Regeneration in a Rat Sciatic Nerve Defect Model. AB - BACKGROUND: The aim of this study was to evaluate the efficacy of autologous fat graft with different surgical repair methods on reconstruction of a 10-mm-long rat sciatic nerve defect model. METHODS: One hundred forty-four sciatic nerves were operated on in 72 Wistar rats. The right limbs were assigned as group A (n = 72) and the left limbs as group B (n = 72). In group B, autologous fat graft was added to the surgical area so as to stay in contact with the coaptation site. Nerve regeneration was evaluated by walking track analysis, Sciatic Functional Index, pin-prick, and electrophysiologic and histologic tests at commencement and at 4 and 12 weeks after the operation. RESULTS: The rats receiving fat graft showed better regeneration, but the difference was only significant according to Sciatic Functional Index and pin-prick test (p < 0.05). Primary repair, autogenous nerve graft, acellularized nerve graft, vein filled with fresh and denatured muscle graft subgroups in group B showed significantly better regeneration than those in group A according to the Sciatic Functional Index (p < 0.05). In terms of latency and amplitude, all subgroups in groups A and B were found significantly different from the commencement of the study, but there was no difference between groups A and B (p < 0.05). CONCLUSIONS: Although there was no significant difference between the groups, rats receiving autologous fat graft showed better regeneration. Combined use of autologous fat graft with surgical repair methods induced significantly better regeneration. It was concluded that autologous fat grafting may have a beneficial effect on nerve regeneration when it is present in the coaptation site during healing. PMID- 26273734 TI - Debridement and Autologous Lipotransfer for Chronic Ulceration of the Diabetic Foot and Lower Limb Improves Wound Healing. AB - BACKGROUND: The application of autologous lipotransfer (fat grafting, lipofilling) in reconstructive surgery is steadily becoming more popular as evidence of the regenerative and reparative effects of fat becomes better known. The authors investigated the use of autologous lipotransfer for treatment of chronic diabetic and other foot and lower limb ulcers. METHODS: Twenty-six patients with nonhealing wounds were treated with surgical debridement and autologous lipotransfer (using the debridement and autologous lipotransfer method). The mean age of the wounds before intervention was 16.7 months. Wound size after debridement averaged 5.1 +/- 2.6 cm2. On average, 7.1 +/- 3.3 cc of lipoaspirate was transferred into the wound area. RESULTS: Twenty-two of 25 wounds (88 percent) healed completely within a mean of 68.0 +/- 33.0 days. A reduction of wound size by 50 percent was achieved after an average of 4 weeks. In one patient with an ulcer within particularly scarred tissues on the lower limb, a repeated session of lipotransfer led to complete wound healing after another 4 weeks. CONCLUSION: The authors describe a simple and useful technique to improve wound healing in diabetic feet and chronic lower limb ulcers with a background of peripheral vascular disease, where other interventional options to achieve wound healing have failed. PMID- 26273735 TI - Is Double-Blinded Peer Review Necessary? The Effect of Blinding on Review Quality. AB - BACKGROUND: The review process can be completely open, double-blinded, or somewhere in between. Double-blinded peer review, where neither the authors' nor peer reviewers' identities are shared with each other, is thought to be the fairest system, but there is evidence that it does not affect reviewer behavior or influence decisions. Furthermore, even without presenting author names, authorship is often apparent to reviewers, especially in small specialties. In conjunction with Plastic and Reconstructive Surgery (PRS), the authors examined the effect of double-blinded review on review quality, reviewer publishing recommendation, and reviewer manuscript rating. The authors hypothesized that double-blinded review will not improve review quality and will not affect recommendation or rating. METHODS: Traditionally, PRS peer review has been conducted in a single-blinded fashion. During a 3-month period of standard operation of the Journal, the authors examined reviews, recommendations, and manuscript ratings. Beginning October 1, 2014, PRS started conducting reviews in a double-blinded manner. The authors examined the additional reviews submitted during a 3-month period after the change. Review quality was assessed using the validated Review Quality Instrument. RESULTS: Double-blinding had no effect on reviewer publishing recommendation or manuscript ranking. Review quality did not improve after the implementation of double-blinded review. Blinding was successful 66 percent of the time. The most common reasons for blinding failure were reviewer familiarity with authors' work and author self-citation. CONCLUSIONS: Double-blinding adds considerable work for authors and editorial staff and has no positive effect on review quality. Furthermore, the authors' results revealed no publication bias based on author identity at PRS. PMID- 26273736 TI - Discussion: Assessing the Impact of Blood Loss in Cranial Vault Remodeling: A Risk Assessment Model Using the 2012 to 2013 Pediatric National Surgical Quality Improvement Program Data Sets. PMID- 26273737 TI - The Role of Long Intergenic Noncoding RNA p21 in Vascular Endothelial Cells. AB - Large intergenic long noncoding RNA p21 (lincRNA-p21) has recently shown to play an important role in biological functions. However, the biological role of lincRNA-p21 in vascular endothelial cells remains unclear. In the present study, we investigated the role of lincRNA-p21 in vascular endothelial cells through gain- and loss-of-function studies and found that lincRNA-p21 promoted cell apoptosis and induced cell cycle progression. Furthermore, lincRNA-p21 acted as an endogenous sponge by directly binding to miR-130b and decreased miR-130b expression. In addition, miR-130b reversed the inhibitory effect of lincRNA-p21 on the growth of vascular endothelial cells. Taken together, our data highlight the pivotal role of lincRNA-p21 in the growth of vascular endothelial cells. PMID- 26273738 TI - Beyond the flavour: a de-flavoured polyphenol rich extract of clove buds (Syzygium aromaticum L) as a novel dietary antioxidant ingredient. AB - Though kitchen spices constitute an important source of dietary antioxidants, their consumption at a physiologically relevant dose is very often hampered by their unpleasant flavour characteristics. The present paper describes a novel approach to derive stable de-flavoured spice extracts with minimised taste and odour profiles which are suitable for impregnation into a variety of food and beverage matrices at physiologically relevant doses. A popular kitchen spice, clove bud (Syzygium aromaticum L), having strong flavour and pungency characteristics was selected in the present study to derive a de-flavoured extract with a standardised polyphenolic profile (Clovinol) and was incorporated into various foods. The antioxidant efficacy of Clovinol on healthy human volunteers who check and answer official emails involving responsibility was investigated by analysing their endogenous antioxidant enzymes and the extent of lipid peroxidation upon consumption of Clovinol either as capsules or in a different food/beverage at 250 mg per serving per day for 30 days. It was observed that Clovinol can be conveniently incorporated in various food matrices without flavour issues and the consumption of such food/beverage items may support an effective detoxification process with an average elevation of 33 +/- 3% in catalase, 66 +/- 8% in SOD, 56 +/- 5% in GPx and 167 +/- 21% in GSH levels, and 81 +/- 11% attenuation in membrane lipid peroxidation level. PMID- 26273740 TI - Letter to the Editor: Chiari malformation I and autism spectrum disorder. PMID- 26273739 TI - Intramuscular Injections Along the Motor End Plates: A Minimally Invasive Approach to Shuttle Tracers Directly into Motor Neurons. AB - Diseases affecting the integrity of spinal cord motor neurons are amongst the most debilitating neurological conditions. Over the last decades, the development of several animal models of these neuromuscular disorders has provided the scientific community with different therapeutic scenarios aimed at delaying or reversing the progression of these conditions. By taking advantage of the retrograde machinery of neurons, one of these approaches has been to target skeletal muscles in order to shuttle therapeutic genes into corresponding spinal cord motor neurons. Although once promising, the success of such gene delivery approach has been hampered by the sub-optimal number of transduced motor neurons it has so far shown to yield. Motor end plates (MEPs) are highly specialized regions on the skeletal musculature that are in direct synaptic contact to the spinal cord alpha motor neurons. In this regard, it is important to note that, so far, the efforts to retrogradely transfer genes into motor neurons were made without reference to the location of the MEP region in the targeted muscles. Here, we describe a simple protocol 1) to reveal the exact location of the MEPs on the surface of skeletal muscles and 2) to use this information to guide the intramuscular delivery and subsequent optimal retrograde transport of retrograde tracers into motor neurons. We hope to utilize the results from these tracing experiments in further studies into investigating retrograde transport of therapeutic genes to spinal cord motor neurons through the targeting of MEPs. PMID- 26273741 TI - Intracranial pressure monitoring among children with severe traumatic brain injury. AB - OBJECT Well-designed studies linking intracranial pressure (ICP) monitoring with improved outcomes among children with severe traumatic brain injury (TBI) are lacking. The main objective of this study was to examine the relationship between ICP monitoring in children and in-hospital mortality following severe TBI. METHODS An observational study was conducted using data derived from 153 adult or mixed (adult and pediatric) trauma centers participating in the American College of Surgeons (ACS) Trauma Quality Improvement Program (TQIP) and 29 pediatric trauma centers participating in the pediatric pilot TQIP between 2010 and 2012. Random-intercept multilevel modeling was used to examine the association between ICP monitoring and in-hospital mortality among children with severe TBI <=16 years of age after adjusting for important confounders. This association was evaluated at the patient level and at the hospital level. In a sensitivity analysis, this association was reexamined in a propensity-matched cohort. RESULTS A total of 1705 children with severe TBI were included in the study cohort. The overall in-hospital mortality was 14.3% of patients (n = 243), whereas the mortality of the 273 patients (16%) who underwent invasive ICP monitoring was 11% (n = 30). After adjusting for patient- and hospital-level characteristics, ICP monitoring was associated with lower in-hospital mortality (adjusted OR 0.50; 95% CI 0.30-0.85; p = 0.01). It is possible that patients who were managed with ICP monitoring were selected because of an anticipated favorable or unfavorable outcome. To further address this potential selection bias, the analysis was repeated with the hospital-specific rate of ICP monitoring use as the exposure. The adjusted OR for death of children treated at high ICP-use hospitals was 0.49 compared with those treated at low ICP-use hospitals (95% CI 0.31-0.78; p = 0.003). Variations in ICP monitoring use accounted for 15.9% of the interhospital variation in mortality among children with severe TBI. Similar results were obtained after analyzing the data using propensity score-matching methods. CONCLUSIONS In this observational study, ICP monitoring use was associated with lower hospital mortality at both the patient and hospital levels. However, the contribution of variable ICP monitoring rates to interhospital variation in pediatric TBI mortality was modest. PMID- 26273742 TI - A Cognitive Paradigm to Investigate Interference in Working Memory by Distractions and Interruptions. AB - Goal-directed behavior is often impaired by interference from the external environment, either in the form of distraction by irrelevant information that one attempts to ignore, or by interrupting information that demands attention as part of another (secondary) task goal. Both forms of external interference have been shown to detrimentally impact the ability to maintain information in working memory (WM). Emerging evidence suggests that these different types of external interference exert different effects on behavior and may be mediated by distinct neural mechanisms. Better characterizing the distinct neuro-behavioral impact of irrelevant distractions versus attended interruptions is essential for advancing an understanding of top-down attention, resolution of external interference, and how these abilities become degraded in healthy aging and in neuropsychiatric conditions. This manuscript describes a novel cognitive paradigm developed the Gazzaley lab that has now been modified into several distinct versions used to elucidate behavioral and neural correlates of interference, by to-be-ignored distractors versus to-be-attended interruptors. Details are provided on variants of this paradigm for investigating interference in visual and auditory modalities, at multiple levels of stimulus complexity, and with experimental timing optimized for electroencephalography (EEG) or functional magnetic resonance imaging (fMRI) studies. In addition, data from younger and older adult participants obtained using this paradigm is reviewed and discussed in the context of its relationship with the broader literatures on external interference and age-related neuro-behavioral changes in resolving interference in working memory. PMID- 26273743 TI - The spatial side of somatoparaphrenia: a case study. AB - The perception of the bodily self in space is a composite cognitive function requiring a dynamic integrated brain mechanism. Somatoparaphrenia (SP), a delusional belief concerning the experienced disownership for the contralesional paralyzed arm, represents the disruption of such mechanism. In two experiments, we have investigated the alteration of limb disownership after spatial manipulations in a right-brain-damaged patient affected by chronic SP. In experiment 1 the patient's spatial attention was switched between the left and right sides of space. SP signs worsened when the patient was interviewed from the left compared to the right bedside. In the second experiment we showed the first systematic transient remission of SP using left caloric vestibular stimulation (CVS), a physiologic manipulation mainly acting on the spatial frame of reference. Taken together, these results shed further light on the spatial nuance of SP and on the importance of vestibular signals for the generation of a coherent body representation. Furthermore, our case study demonstrated the possibility of eliciting more severe SP signs if the patient is interviewed from the left bedside. Additionally, CVS applications may have an important impact on the rehabilitation of these symptoms. PMID- 26273744 TI - Anesthesia and Poliomyelitis: A Matched Cohort Study. AB - BACKGROUND: Poliomyelitis is a viral infectious disease caused by 1 of the 3 strains of poliovirus. The World Health Organization launched an eradication campaign in 1988. Although the number of cases of poliomyelitis has drastically declined, eradication has not yet been achieved, and there are a substantial number of survivors of the disease. Survivors of poliomyelitis present a unique set of challenges to the anesthesiologist. The scientific literature regarding the anesthetic management of survivors of poliomyelitis, however, is limited and primarily experiential in nature. Using a retrospective, matched cohort study, we sought to more precisely characterize the anesthetic implications of poliomyelitis and to determine what risks, if any, may be present for patients with a history of the disease. METHODS: Using the Mayo Clinic Life Sciences System Data Discovery and Query Builder, study subjects were identified as those with a history of paralytic poliomyelitis who had undergone major surgery at Mayo Clinic Rochester between 2005 and 2009. For each case, 2 sex- and age-matched controls that underwent the same surgical procedure during the study period were randomly selected from a pool of possible controls. Medical records were manually interrogated with respect to demographic variables, comorbid conditions, operative and anesthetic course, and postoperative course. RESULTS: We analyzed 100 cases with 2:1 matched controls and found that the peri- and postoperative courses were very similar for both groups of patients. Pain scores, postanesthesia care unit admission, length of postanesthesia care unit stay, intensive care unit admission, length of intensive care unit stay, and initial extubation location were not significantly different between the 2 groups. Looking at pulmonary complications in our primary outcome, there was no significant difference between the 2 groups (17% vs 14% for polio versus control, respectively; conditional logistic regression odds ratio = 1.5; 95% confidence interval, 0.7-3.3; P = 0.33). In addition, no difference was noted in those requiring a code or rapid response team intervention (4% vs 3% for polio versus control; P = 0.46) and the 30-day mortality rate was also not significantly different, with 2% of polio patients dying compared with 3% of controls (P = 0.79). The analysis of the primary outcome was repeated for the subset of patients with a history of poliomyelitis who had persistent neurologic deficits preoperatively (n = 36) and their matched controls (n = 72). In this subset analysis, there were 4 (11%) polio patients and 8 (11%) control patients who experienced pulmonary complications (conditional logistic regression odds ratio = 1.00; 95% confidence interval, 0.27-3.72; P = 1.00). The percentage of patients experiencing specific pulmonary complications of interest was similar between groups (postoperative mechanical ventilation: 6% vs 8% for polio and control patients, respectively; prolonged mechanical ventilation: 0% vs 1%; reintubation: 8% vs 4%; pulmonary infection: 6% vs 6%; and aspiration: 0% vs 1%). CONCLUSIONS: This study suggests that patients with a history of poliomyelitis do not seem to have an increased risk of pulmonary complications in the perioperative period. However, an odds ratio as great as 3.3-fold may be present. PMID- 26273745 TI - Stridor in Neonates After Using the Microcuff(r) and Uncuffed Tracheal Tubes: A Retrospective Review. AB - BACKGROUND: We conducted a retrospective chart review to determine the frequency of stridor and contributing factors after the use of Microcuff(r) and uncuffed tracheal tubes (TTs) in neonates. METHODS: All neonates in our neonatal intensive care unit whose airways were intubated between May 2011 and June 2012 were included. Data were collected from the neonatal intensive care unit database and from the electronic anesthesia record. Extracted data included postmenstrual age (PMA) at birth, birth weight, TT size and type, duration of tracheal intubation, and number of reintubations. The use of racemic epinephrine, heliox, and/or dexamethasone postextubation was considered diagnostic of stridor. RESULTS: Of the 324 neonates whose data were reviewed, 27 (8.3%) developed postextubation stridor. Neonates who developed stridor were more premature (PMA at birth, 29.9 +/- 5.8 vs 33.0 +/- 4.8 weeks, P = 0.001), had a lower birth weight (1.56 +/- 1.07 vs 2.02 +/- 0.96 kg, P = 0.005), greater duration of intubation (median: 20 vs 3 days, P < 0.0001), and multiple reintubations (median: 2 vs 0, P < 0.0001). The frequency of stridor was 17.2% after using Microcuff TT and 7.5% after using uncuffed TTs (Fisher exact test, 2-sided P = 0.08 [95% confidence interval for difference in proportions: -9.4% to 28.7%]). In a multivariable logistic regression model, after adjusting for PMA, birth weight, duration of intubation, and number of reintubations, the use of a Microcuff TT was associated with increased odds of stridor (adjusted odds ratio = 9.27 [95% confidence interval: 1.88-45.67], P = 0.006). CONCLUSIONS: The use of the Microcuff TT is associated with increased odds of postextubation stridor in neonates compared with the use of uncuffed TT. PMID- 26273746 TI - Continuous Spinal Analgesia for Labor and Delivery: An Observational Study with a 23-Gauge Spinal Catheter. AB - BACKGROUND: The aim of the study was to assess postdural puncture headache, pain relief, motor blockade, and success rate of conversion to cesarean delivery anesthesia of a 23-gauge spinal catheter (Wiley Spinal(r)) for labor analgesia. METHODS: After insertion of the spinal catheter, intrathecal bupivacaine 2.5 mg was administered, followed by patient-controlled intrathecal analgesia (basal infusion of 0.0625% bupivacaine with fentanyl 2 MUg/mL at a rate of 2 mL/h, demand bolus 1 mL, lockout interval 20 minutes). Bupivacaine 0.5%, up to 25 mg, was administered via the catheter along with fentanyl 20 MUg for cesarean delivery anesthesia, if necessary. The catheter was removed after delivery or after 12 hours, whichever was longer. RESULTS: One hundred thirteen women were enrolled. In 12 women (11%), the catheter was not successfully inserted or maintained in position. Continuous spinal analgesia was used in 101 women. Three women (2.6%, 95% confidence interval, 0.7%-8.1%) developed postdural puncture headache. There were 83 spontaneous, 12 operative vaginal, and 18 cesarean deliveries. Of the 18 cesarean deliveries, 16 had continuous spinal analgesia when the decision was made to perform a cesarean delivery; conversion from labor analgesia to cesarean anesthesia was successful in 15 women (94%, 95% confidence interval, 67.7%-99.7%). CONCLUSIONS: The 23-gauge spinal catheter can be used for analgesia for labor. It can also be converted to surgical anesthesia for cesarean deliveries. Further studies are warranted to determine whether the spinal catheter will be a useful addition to the neuraxial techniques available for obstetric anesthesia care. PMID- 26273747 TI - The Effect of Low-Dose Dexmedetomidine as an Adjuvant to Levobupivacaine in Patients Undergoing Vitreoretinal Surgery Under Sub-Tenon's Block Anesthesia. AB - BACKGROUND: This study evaluated the motor and sensory block durations and the postoperative analgesic effects of adding dexmedetomidine to levobupivacaine for sub-Tenon's block anesthesia in patients undergoing vitreoretinal surgery. Motor and sensory block durations were considered as a primary end point. METHODS: Sixty ASA physical status I to III patients subjected to vitreoretinal surgery under sub-Tenon's block anesthesia were randomly divided equally into 2 groups, depending on the local anesthesia solution used, to receive 4 mL of 0.75% levobupivacaine plus 15 IU hyaluronidase diluted with 1 mL normal saline (group L) or 4 mL of 0.75% levobupivacaine plus 15 IU hyaluronidase and 20 MUg dexmedetomidine diluted with 1 mL normal saline (group LD). The total volume of the local anesthesia solution used was 5 mL. Motor block and sensory block durations were evaluated until the return of normal motor and sensory functions. The sedation level was assessed during the surgery period and 24 hours postoperatively, together with the degree of postoperative pain. The total diclofenac consumption (milligrams) and the number of patients (%) who required tramadol were recorded. The sleep quality of the first postoperative night was assessed using the Consensus Sleep Diary. RESULTS: Dexmedetomidine provided significantly longer motor block duration (371.90 +/- 48.10 vs 264.13 +/- 41.48 minutes, P = 0.001) and significantly longer sensory block duration (499.10 +/- 51.76 vs 344.33 +/- 45.46 minutes, P = 0.001) compared with levobupivacaine alone. Furthermore, the patients in the dexmedetomidine group achieved significantly (P < 0.0001) greater levels of sedation during the surgery period and for 12 hours postoperatively together with significantly (P < 0.0001) lower values of verbal numeric rating scale of pain between the periods from 4 to 12 hours postoperatively compared with the patients in the levobupivacaine group. There was significantly (P = 0.001) less diclofenac consumed (mg) in the dexmedetomidine group. The patients in the dexmedetomidine group reported significantly higher rates of good sleep quality on the first postoperative night (70%) compared with those in the levobupivacaine group (30%; P < 0.0001). CONCLUSIONS: For patients undergoing vitreoretinal surgery, adding 20 MUg of dexmedetomidine to levobupivacaine for sub-Tenon's block anesthesia in vitreoretinal surgery extended the motor and sensory block durations and provided more effective postoperative analgesia with improvement in the sleep quality in the first postoperative night compared with levobupivacaine alone. PMID- 26273748 TI - Neuropeptide VF Enhances Cannabinoid Agonist WIN55,212-2-Induced Antinociception in Mice. AB - BACKGROUND: Cannabinoids produce analgesia in several pain models, but the undesirable side effects from high doses of cannabinoid drugs limit their clinic use. Our recent results indicate that cannabinoid-induced antinociception was enhanced by neuropeptide VF (NPVF). Here, we investigate whether low-dose cannabinoid agonists combined with NPVF can produce effective antinociception with limited side effects. METHODS: The in vivo properties of (R)-(-1)-[2,3 dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1 napthalenylmethanone (WIN55,212-2) given alone and its combination with NPVF were evaluated in nociceptive modulation, locomotor activity, gastrointestinal transit, and tolerance development assays after intracerebroventricular administration in mice. RESULTS: In the radiant tail-flick test, the antinociception of combination of WIN55,212-2 and NPVF was more potent than that of cannabinoid agonist given alone, with an ED50 shift from 3.51 to 0.69 nmol; 9 nmol WIN55,212-2 alone and 3 nmol WIN55,212-2 combined with NPVF induced equivalent antinociception after supraspinal administration. The cannabinoid potentiating effects of NPVF were reduced by both the cannabinoid receptor type 1 and the neuropeptide FF receptor antagonists. In the formalin assay, WIN55,212-2 combined with NPVF also significantly reduced pain-related behaviors. However, the combination of WIN55,212-2 with NPVF exerted significant hypoactivity in a manner similar to high doses of WIN55,212-2. It was important to note that the combination of WIN55,212-2 with NPVF produced nontolerance-forming antinociception and weaker inhibition of gastrointestinal transit compared with high dose of WIN55,212-2. CONCLUSIONS: These data suggest that the cannabinoid agonist combined with NPVF produces effective antinociception-lacking tolerance via both cannabinoid receptor type 1 and neuropeptide FF receptors in the brain. PMID- 26273749 TI - Interaction Effects of Acute Kidney Injury, Acute Respiratory Failure, and Sepsis on 30-Day Postoperative Mortality in Patients Undergoing High-Risk Intraabdominal General Surgical Procedures. AB - BACKGROUND: Acute kidney injury (AKI), acute respiratory failure, and sepsis are distinct but related pathophysiologic processes. We hypothesized that these 3 processes may interact to synergistically increase the risk of short-term perioperative mortality in patients undergoing high-risk intraabdominal general surgery procedures. METHODS: We performed a retrospective, observational cohort study of data (2005-2011) from the American College of Surgeons-National Surgical Quality Improvement Program, a high-quality surgical outcomes data set. High-risk procedures were those with a risk of AKI, acute respiratory failure, or sepsis greater than the average risk in all intraabdominal general surgery procedures. The effects of AKI, acute respiratory failure, and sepsis on 30-day mortality were assessed using a Cox proportional hazards model. Additive interactions were assessed with the relative excess risk due to interaction. RESULTS: Of 217,994 patients, AKI, acute respiratory failure, and sepsis developed in 1.3%, 3.7%, and 6.8%, respectively. The 30-day mortality risk with sepsis, acute respiratory failure, and AKI were 11.4%, 24.1%, and 25.1%, respectively, compared with 0.85% without these complications. The adjusted hazard ratios and 95% confidence intervals for a single complication (versus no complication) on mortality were 7.24 (6.46-8.11), 10.8 (8.56-13.6), and 14.2 (12.8-15.7) for sepsis, AKI, and acute respiratory failure, respectively. For 2 complications, the adjusted hazard ratios were 30.8 (28.0-33.9), 42.6 (34.3-52.9), and 65.2 (53.9-78.8) for acute respiratory failure/sepsis, AKI/sepsis, and acute respiratory failure/AKI, respectively. Finally, the adjusted hazard ratio for all 3 complications was 105 (92.8-118). Positive additive interactions, indicating synergism, were found for each combination of 2 complications. The relative excess risk due to interaction for all 3 complications was not statistically significant. CONCLUSIONS: In high risk general surgery patients, the development of AKI, acute respiratory failure, or sepsis is independently associated with an increase in 30-day mortality. In addition, the development of 2 complications shows significant positive additive interactions to further increase the risk of mortality. Our findings suggest that interactions between these 3 perioperative complications increase the risk of mortality more than would be expected by the independent effects of each complication alone. PMID- 26273750 TI - Xenon Anesthesia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. AB - BACKGROUND: Xenon anesthesia has been studied for decades. However, no meta analysis of randomized controlled trials (RCTs) on xenon anesthesia has been conducted. The aim of this study was to systematically review all available evidence from RCTs comparing xenon and other inhaled and IV anesthetics on anesthetic outcomes. Our meta-analysis attempted to quantify the effects of xenon anesthesia on clinical outcomes in relation to other anesthetics. METHODS: We found 43 RCTs from PubMed, MEDLINE, CENTRAL, EMBASE, and CINAHL (until January 2015). A total of 31 studies comparing xenon (841 patients) with other inhaled agents (836 patients) and 12 studies comparing xenon (373 patients) with propofol (360 patients) were found. We evaluated clinical outcomes, such as intraoperative hemodynamics, emergence, and postoperative nausea and vomiting (PONV). RESULTS: Patients undergoing xenon anesthesia had a lower heart rate and higher mean arterial pressure (MAP) intraoperatively than those receiving volatile anesthesia (mean difference = -6 min-1 [99% confidence interval {99% CI} -10.0 to -2.3]; mean difference = 9 mm Hg [99% CI 3.1-14.4]) and propofol anesthesia (mean difference = -10 min-1 [99% CI -12.4 to -6.6]; mean difference = 7 mm Hg [99% CI 0.85-13.2]). Compared with baseline, intraoperative MAP remained relatively stable (change < 5.5%, 99% CI within +/-20% of the baseline) under xenon anesthesia, but MAP decreased by >=15% under volatile (mean difference = -17 mm Hg [99% CI -29.5 to - 4.9], percentage change = -17.5%) and propofol (mean difference = -14 mm Hg [99% CI -26.1 to -2.5], percentage change = -15.0%) anesthesia. Patients had faster emergence from xenon than from volatile anesthesia: eyes opening (versus all volatile agents: mean 4 vs 7 minutes, percentage change = -49.8% [99% CI -55.1% to -44.0%]), tracheal extubation (versus all volatile agents: mean 4 vs 8 minutes percentage change = -44.6% [99% CI -57.3% to -28.1%]), orientation (versus sevoflurane: mean 5 vs 10 minutes, percentage change = -45.1% [99% CI -58.5% to -28.1%]), countdown (versus sevoflurane: mean 6 vs 10 minutes, percentage change = -41.7% [99% CI -50.3% to 31.6%]; versus isoflurane: mean 6 vs 14 minutes, percentage change = -57.7% [99% CI -65.7% to -48.3%]), and reaction on demand (versus sevoflurane: mean 4 vs 8 minutes, percentage change = -53.2% [99% CI -65.7% to -35.6%]). However, xenon anesthesia increased the risks of PONV (incidence 34.4% vs 19.9%; risk ratio = 1.72 [99% CI 1.10-2.69], risk difference = 0.19 [99% CI 0.04-0.33]). CONCLUSIONS: Xenon anesthesia provides relatively more stable intraoperative blood pressure, lower heart rate, and faster emergence from anesthesia than volatile and propofol anesthesia. However, xenon is associated with a higher incidence of PONV. PMID- 26273751 TI - Molecular Dynamics Simulations of Poly(ethylene oxide) Grafted onto Silica Immersed in Melt of Homopolymers. AB - Tuning of surface properties plays an important role in applications ranging from material engineering to biomedicine/chemistry. The interactions of chains grafted to a solid support and exposed to a matrix of chemically identical chains represent an intriguing issue. In this work, the behavior of poly(ethylene oxide) (PEO) chains grafted irreversibly onto an amorphous silica and immersed in the matrix of free PEO chains of different polymerization degree is studied using molecular dynamics simulations. The density distributions of grafted and free PEO chains, the height of the grafted layer, overlap parameters, and orientation order parameters depend not only on the grafting density but also on the length of free chains which confirm the entropic nature of the interactions between the grafted and free chains. In order to achieve a complete expulsion of the free chains from the grafted layer, a grafting density as high as 3.5 nm(-2) is necessary. Free PEO chains of 9 monomers leave the grafted layer at lower grafting densities than the longer PEO chains of 18 monomers in contrast with the theoretical predictions. The height of the grafted layer evolves with the grafting density in the presence of free chains in qualitative agreement with the theoretical phase diagram. PMID- 26273752 TI - Development of a real-time immuno-PCR assay for the quantification of 17beta estradiol in water. AB - A competitive real-time (RT) immuno-polymerase chain reaction (iPCR) (RT-iPCR) assay was developed for the sensitive quantification of 17beta-estradiol in water. Using a universal iPCR method and polyclonal antibodies, 17beta-estradiol was accurately quantified at concentrations ranging from 1 pg mL(-1) to 10 ug mL( 1). The RT-iPCR assay's limit of detection was 0.7 pg mL(-1). The RT-iPCR assay provided an 800-fold increase in sensitivity as well as an expanded working range compared with the corresponding enzyme-linked immunosorbent assay. Assay cross reactivity to estrone and estriol, two structurally related estrogens, was below 8%. Water samples spiked with 17beta-estradiol were analyzed by RT-iPCR to determine the assay's potential as a rapid screen for the monitoring of manure borne estrogens in the environment. The assay showed recoveries of 82, 102 and 103% for Milli-Q, tap, and irrigation water, respectively, without requiring sample extraction or concentration prior to analysis. PMID- 26273753 TI - Secretory expression of organophosphorus hydrolase OPHC2 in Yarrowia lipolytica Polg. AB - In the present study, recombinant organophosphorus hydrolase OPHC2 was successfully produced by Yarrowia lipolytica and purified. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and western blot analyses showed a major polypeptide band of 36 kDa. The purified enzyme was optimally active at 65 degrees C and pH 8.5 and also displayed good thermal and pH stability using methyl parathion (O,O-dimethyl-O-4-p-nitrophenyl phosphorothioate) as a substrate. Moreover, as Y. lipolytica is a non-pathogenic, generally regarded as safe (GRAS) yeast, the cell culture supernatant can be used directly on vegetables and fruits that are contaminated by organophosphorus pesticides. PMID- 26273754 TI - The effect of thiacloprid formulation on DNA/chromosome damage and changes in GST activity in bovine peripheral lymphocytes. AB - The potential genotoxic effect of thiacloprid formulation on bovine peripheral lymphocytes was evaluated using the comet assay and the cytogenetic endpoints: chromosome aberrations (CAs), sister chromatid exchanges (SCEs) and micronuclei (MNi). Whole blood cultures were treated with the insecticide at concentrations of 30, 60, 120, 240 and 480 MUg mL(-1) for 24, 48 h and/or 2 h of incubation. A statistically significant increase in the frequency of DNA damage, as well as in unstable chromosome aberrations (% breaks) were found after exposure to the insecticide at concentrations ranging from 120 to 480 MUg mL(-1) (P < 0.05, P < 0.01, P < 0.001). For the detection of stable structural chromosome aberrations (e.g., translocations) and numerical aberrations by the FISH method, three whole chromosome painting probes for bovine chromosomes 1, 5 and 7 (BTA1, BTA5 and BTA7) were used in our experiments. We observed numerical aberrations, but without any statistical significance. Regarding the sister chromatid exchanges, no significant elevation in the SCE frequencies was found after 24-h exposure to the insecticide. A dose-related response in the SCE induction was obtained in bovine cultures after the prolonged time of exposure (48 h) to thiacloprid formulation at concentrations ranging from 120 to 480 MUg mL(-1) in each donor (P < 0.05, P < 0.01), which was associated with a reduction of the PI (P < 0.05, P < 0.01). The insecticide failed to produce MNi; however, a significant reduction of CBPI was observed. Using real-time PCR, a decrease in the expression of bovine glutathione S-transferase M3 (GSTM3) was detected at the lowest dose. The higher concentrations of thiacloprid formulation caused an increase in the mRNA expression. PMID- 26273755 TI - The platelet-activating factor acetylhydrolase gene derived from Trichoderma harzianum induces maize resistance to Curvularia lunata through the jasmonic acid signaling pathway. AB - Platelet-activating factor acetylhydrolase (PAF-AH) derived from Trichoderma harzianum was upregulated by the interaction of T. harzianum with maize roots or the foliar pathogen Curvularia lunata. PAF-AH was associated with chitinase and cellulase expressions, but especially with chitinase, because its activity in the KO40 transformant (PAF-AH disruption transformant) was lower, compared with the wild-type strain T28. The result demonstrated that the colonization of maize roots by T. harzianum induced systemic protection of leaves inoculated with C. lunata. Such protection was associated with the expression of inducible jasmonic acid pathway-related genes. Moreover, the data from liquid chromatography-mass spectrometry confirmed that the concentration of jasmonic acid in maize leaves was associated with the expression level of defense-related genes, suggesting that PAF-AH induced resistance to the foliar pathogen. Our findings showed that PAF-AH had an important function in inducing systemic resistance to maize leaf spot pathogen. PMID- 26273756 TI - Kinetics of aerobic and anaerobic biomineralization of atrazine in surface and subsurface agricultural soils in Ohio. AB - The purpose of this study was to assess atrazine mineralization in surface and subsurface samples retrieved from vertical cores of agricultural soils from two farm sites in Ohio. The Defiance site (NW-Ohio) was on soybean-corn rotation and Piketon (S-Ohio) was on continuous corn cultivation. Both sites had a history of atrazine application for at least a couple of decades. The clay fraction increased at the Defiance site and the organic matter and total N content decreased with depth at both sites. Mineralization of atrazine was assessed by measurement of (14)CO2 during incubation of soil samples with [U-ring-(14)C] atrazine. Abiotic mineralization was negligible in all soil samples. Aerobic mineralization rate constants declined and the corresponding half-lives increased with depth at the Defiance site. Anaerobic mineralization (supplemented with nitrate) was mostly below the detection at the Defiance site. In Piketon samples, the kinetic parameters of aerobic and anaerobic biomineralization of atrazine displayed considerable scatter among replicate cores and duplicate biometers. In general, this study concludes that data especially for anaerobic biomineralization of atrazine can be more variable as compared to aerobic conditions and cannot be extrapolated from one agricultural site to another. PMID- 26273757 TI - Uptake, translocation, and control of trumpet flower (Tecoma stans) with aminocyclopyrachlor. AB - To gain a better understanding of the physiology of the herbicide aminocyclopyrachlor in young plants of trumpet flower, the uptake and translocation were evaluated after the application of herbicide. This was determined by treating individual leaves with formulated herbicides plus (14)C aminocyclopyrachlor after the application of the formulated herbicide. This experiment used a randomized experimental design with three replications. In addition, field studies were conducted to assess the effectiveness of foliar applications of aminocyclopyrachlor in association with metsulfuton-methyl. The plant absorbed 20% of the herbicide applied. The translocation percentage did not surpass 5% of the total amount applied. Only 1% of the herbicide applied was translocated to the roots. Rate of 40 + 13 g a.i. 100 L(-1) of aminocyclopyrachlor+metsulfuron-methyl was effective to control T. stans. PMID- 26273758 TI - Fecal contamination in irrigation water and microbial quality of vegetable primary production in urban farms of Metro Manila, Philippines. AB - Microbial contamination of fresh produce can present a severe risk to public health. By conducting a rigorous survey of irrigation waters, the impacts of fecal contamination on the quality of produce could be assessed. In this study, surface waters were observed to be contaminated with Escherichia coli, Salmonella spp., and somatic coliphages. Culture methods show that out of 373 irrigation water, soil, and vegetable samples collected for a 1-year period, 232 (62.20%) were found positive for E. coli, 213 (57.26%) for somatic coliphages, and 2 (0.53%) for Salmonella spp. Out of 190 water samples, 167 (87.9%) were found to have E.coli, 174 (91.6%) have somatic coliphages, and 1 (0.5%) with Salmonella spp. In soil samples, 36 of 91 (39.6%) have E. coli, 31 (34.0%) have somatic coliphages, and none with Salmonella spp. Lastly, out of 92 vegetable samples, 29 (31.5%), 8 (8.7%), and 1 (1.1%) were found to have E. coli, somatic coliphages, and Salmonella spp., respectively. Molecular analysis confirmed the presence of bacterial contaminants. Seasonal weather conditions were noted to have an effect on the presence and number of these fecal indicator organisms. The observed data suggest that contaminated irrigation water may greatly affect the quality of fresh produce from these agricultural operations. PMID- 26273759 TI - Application of chemometric analysis based on physicochemical and chromatographic data for the differentiation origin of plant protection products containing chlorpyrifos. AB - The aim of this study was to investigate the similarities and dissimilarities between the pesticide samples in form of emulsifiable concentrates (EC) formulation containing chlorpyrifos as active ingredient coming from different sources (i.e., shops and wholesales) and also belonging to various series. The results obtained by the Headspace Gas Chromatography-Mass Spectrometry method and also some selected physicochemical properties of examined pesticides including pH, density, stability, active ingredient and water content in pesticides tested were compared using two chemometric methods. Applicability of simple cluster analysis and also principal component analysis of obtained data in differentiation of examined plant protection products coming from different sources was confirmed. It would be advantageous in the routine control of originality and also in the detection of counterfeit pesticides, respectively, among commercially available pesticides containing chlorpyrifos as an active ingredient. PMID- 26273761 TI - Metal/organo relay catalysis in a one-pot synthesis of methyl 4-aminopyrrole-2 carboxylates from 5-methoxyisoxazoles and pyridinium ylides. AB - Methyl 4-aminopyrrole-2-carboxylates were synthesized in one-pot mode by the relay catalytic cascade reaction of 5-methoxyisoxazoles with pyridinium ylides by the use of a FeCl2/Et3N binary catalytic system leading to 1-(5-methoxycarbonyl 1H-pyrrol-3-yl)pyridinium salts followed by hydrazinolysis. The approach permits the introduction of a substituent at the pyrrole nitrogen via a nucleophilic reaction of the pyrrolylpyridinium ylide derived from the salt. Catalytic reduction of the ylides gives methyl 4-piperidinopyrrole-2-carboxylates. PMID- 26273762 TI - Reliability assessment of a novel cervical spine deformity classification system. AB - OBJECT: Despite the complexity of cervical spine deformity (CSD) and its significant impact on patient quality of life, there exists no comprehensive classification system. The objective of this study was to develop a novel classification system based on a modified Delphi approach and to characterize the intra- and interobserver reliability of this classification. METHODS: Based on an extensive literature review and a modified Delphi approach with an expert panel, a CSD classification system was generated. The classification system included a deformity descriptor and 5 modifiers that incorporated sagittal, regional, and global spinopelvic alignment and neurological status. The descriptors included: "C," "CT," and "T" for primary cervical kyphotic deformities with an apex in the cervical spine, cervicothoracic junction, or thoracic spine, respectively; "S" for primary coronal deformity with a coronal Cobb angle >= 15 degrees ; and "CVJ" for primary craniovertebral junction deformity. The modifiers included C2-7 sagittal vertical axis (SVA), horizontal gaze (chin-brow to vertical angle [CBVA]), T1 slope (TS) minus C2-7 lordosis (TS-CL), myelopathy (modified Japanese Orthopaedic Association [mJOA] scale score), and the Scoliosis Research Society (SRS)-Schwab classification for thoracolumbar deformity. Application of the classification system requires the following: 1) full-length standing posteroanterior (PA) and lateral spine radiographs that include the cervical spine and femoral heads; 2) standing PA and lateral cervical spine radiographs; 3) completed and scored mJOA questionnaire; and 4) a clinical photograph or radiograph that includes the skull for measurement of the CBVA. A series of 10 CSD cases, broadly representative of the classification system, were selected and sufficient radiographic and clinical history to enable classification were assembled. A panel of spinal deformity surgeons was queried to classify each case twice, with a minimum of 1 intervening week. Inter- and intrarater reliability measures were based on calculations of Fleiss k coefficient values. RESULTS: Twenty spinal deformity surgeons participated in this study. Interrater reliability (Fleiss k coefficients) for the deformity descriptor rounds 1 and 2 were 0.489 and 0.280, respectively, and mean intrarater reliability was 0.584. For the modifiers, including the SRS-Schwab components, the interrater (round 1/round 2) and intrarater reliabilities (Fleiss k coefficients) were: C2-7 SVA (0.338/0.412, 0.584), horizontal gaze (0.779/0.430, 0.768), TS-CL (0.721/0.567, 0.720), myelopathy (0.602/0.477, 0.746), SRS-Schwab curve type (0.590/0.433, 0.564), pelvic incidence-lumbar lordosis (0.554/0.386, 0.826), pelvic tilt (0.714/0.627, 0.633), and C7-S1 SVA (0.071/0.064, 0.233), respectively. The parameter with the poorest reliability was the C7-S1 SVA, which may have resulted from differences in interpretation of positive and negative measurements. CONCLUSIONS: The proposed classification provides a mechanism to assess CSD within the framework of global spinopelvic malalignment and clinically relevant parameters. The intra- and interobserver reliabilities suggest moderate agreement and serve as the basis for subsequent improvement and study of the proposed classification. PMID- 26273763 TI - The role of sacral slope in lumbosacral fusion: a biomechanical study. AB - OBJECT: Abnormal sacral slope (SS) has shown to increase progression of spondylolisthesis, yet there exists a paucity in biomechanical studies investigating its role in the correction of adult spinal deformity, its influence on lumbosacral shear, and its impact on the instrumentation selection process. This in vitro study investigates the effect of SS on 3 anterior lumbar interbody fusion constructs in a biomechanics laboratory. METHODS: Nine healthy, fresh frozen, intact human lumbosacral vertebral segments were tested by applying a 550 N axial load to specimens with an initial SS of 20 degrees on an MTS Bionix test system. Testing was repeated as SS was increased to 50 degrees , in 10 degrees increments, through an angulated testing fixture. Specimens were instrumented using a standalone integrated spacer with self-contained screws (SA), an interbody spacer with posterior pedicle screws (PPS), and an interbody spacer with anterior tension band plate (ATB) in a randomized order. Stiffness was calculated from the linear portion of the load-deformation curve. Ultimate strength was also recorded on the final construct of all specimens (n = 3 per construct) with SS of 40 degrees . RESULTS: Axial stiffness (N/mm) of the L5-S1 motion segment was measured at various angles of SS: for SA 292.9 +/- 142.8 (20 degrees ), 277.2 +/- 113.7 (30 degrees ), 237.0 +/- 108.7 (40 degrees ), 170.3 +/ 74.1 (50 degrees ); for PPS 371.2 +/- 237.5 (20 degrees ), 319.8 +/- 167.2 (30 degrees ), 280.4 +/- 151.7 (40 degrees ), 233.0 +/- 117.6 (50 degrees ); and for ATB 323.9 +/- 210.4 (20 degrees ), 307.8 +/- 125.4 (30 degrees ), 249.4 +/- 126.7 (40 degrees ), 217.7 +/- 99.4 (50 degrees ). Axial compression across the disc space decreased with increasing SS, indicating that SS beyond 40 degrees threshold shifted L5-S1 motion into pure shear, instead of compression-shear, defining a threshold. Trends in ultimate load and displacement differed from linear stiffness with SA > PPS > ATB. CONCLUSIONS: At larger SSs, bilateral pedicle screw constructs with spacers were the most stable; however, none of the constructs were significantly stiffer than intact segments. For load to failure, the integrated spacer performed the best; this may be due to angulations of integrated plate screws. Increasing SS significantly reduced stiffness, which indicates that surgeons need to consider using more aggressive fixation techniques. PMID- 26273765 TI - Downsizing the target: the underwater closure technique. PMID- 26273766 TI - An alternative treatment for postcholecystectomy Mirizzi's syndrome: cystic duct balloon dilation. PMID- 26273764 TI - Intraspinal pressure and spinal cord perfusion pressure after spinal cord injury: an observational study. AB - OBJECT: In contrast to intracranial pressure (ICP) in traumatic brain injury (TBI), intraspinal pressure (ISP) after traumatic spinal cord injury (TSCI) has not received the same attention in terms of waveform analysis. Based on a recently introduced technique for continuous monitoring of ISP, here the morphological characteristics of ISP are observationally described. It was hypothesized that the waveform analysis method used to assess ICP could be similarly applied to ISP. METHODS: Data included continuous recordings of ISP and arterial blood pressure (ABP) in 18 patients with severe TSCI. RESULTS: The morphology of the ISP pulse waveform resembled the ICP waveform shape and was composed of 3 peaks representing percussion, tidal, and dicrotic waves. Spectral analysis demonstrated the presence of slow, respiratory, and pulse waves at different frequencies. The pulse amplitude of ISP was proportional to the mean ISP, suggesting a similar exponential pressure-volume relationship as in the intracerebral space. The interaction between the slow waves of ISP and ABP is capable of characterizing the spinal autoregulatory capacity. CONCLUSIONS: This preliminary observational study confirms morphological and spectral similarities between ISP in TSCI and ICP. Therefore, the known methods used for ICP waveform analysis could be transferred to ISP analysis and, upon verification, potentially used for monitoring TSCI patients. PMID- 26273767 TI - Blue rubber bleb nevus syndrome: combined surgical and endoscopic treatment. PMID- 26273768 TI - Complete endoscopic closure of a large gastric defect with endoloop and endoclips after complex endoscopic submucosal dissection. PMID- 26273769 TI - Near-fatal hemorrhagic shock after endoscopic ultrasound-guided liver biopsy. PMID- 26273770 TI - Endoscopic view in a patient with acute gastric volvulus. PMID- 26273771 TI - Double-balloon enteroscopy-assisted endoscopic retrograde cholangiography for the treatment of a strictured Roux-en-Y hepaticojejunal anastomosis. PMID- 26273772 TI - Endoscopic management of obstructive pancreatitis with a metal stent in two family members with hereditary cationic trypsinogen (PRSS1) deficiency. PMID- 26273773 TI - A case of delayed bleeding after endoscopic submucosal dissection for completely circumferential esophageal cancer. PMID- 26273774 TI - Peroral endoscopic myotomy for esophageal muscular ring. PMID- 26273775 TI - Endovascular coil migration and upper gastrointestinal bleed: a causal or casual relationship? PMID- 26273776 TI - Pneumoperitoneum due to a necrotic cavity wall perforation seen at endoscopic necrosectomy. PMID- 26273777 TI - An unusual retroperitoneal lesion causing recurrent acute pancreatitis. PMID- 26273778 TI - Endoscopic ultrasound-guided gastroenterostomy using a lumen-apposing self expanding metal stent for decompression of afferent loop obstruction. PMID- 26273779 TI - Endoscopic ultrasound-guided drainage of a right liver abscess with a self expandable metallic stent. PMID- 26273780 TI - A cholecystocolonic fistula caused by penetration of a double-pigtail plastic stent after endoscopic transpapillary gallbladder stenting. PMID- 26273781 TI - A simple ex vivo, biologic ERCP training model for sphincterotomy. PMID- 26273782 TI - Diagnosing pseudoaneurysm of the gastroduodenal artery on endoscopic ultrasound. PMID- 26273783 TI - Endoscopic extraction of a fish bone with a Foley catheter after endovascular stent graft placement for penetrating aortoesophageal injury. PMID- 26273784 TI - Endoscopic characterization and resection of Vanek's tumor of the duodenum. PMID- 26273785 TI - Endoscopic vacuum therapy in Boerhaave's syndrome with open-pore polyurethane foam and a new open-pore film drainage. PMID- 26273786 TI - High indoor CO2 concentrations in an office environment increases the transcutaneous CO2 level and sleepiness during cognitive work. AB - The purpose of this study is to perform a multiparametric analysis on the environmental factors, the physiological stress reactions in the body, the measured alertness, and the subjective symptoms during simulated office work. Volunteer male subjects were monitored during three 4-hr work meetings in an office room, both in a ventilated and a non-ventilated environment. The environmental parameters measured included CO(2), temperature, and relative humidity. The physiological test battery consisted of measuring autonomic nervous system functions, salivary stress hormones, blood's CO(2)- content and oxygen saturation, skin temperatures, thermal sensations, vigilance, and sleepiness. The study shows that we can see physiological changes caused by high CO(2) concentration. The findings support the view that low or moderate level increases in concentration of CO(2) in indoor air might cause elevation in the blood's transcutaneously assessed CO(2). The observed findings are higher CO(2) concentrations in tissues, changes in heart rate variation, and an increase of peripheral blood circulation during exposure to elevated CO(2) concentration. The subjective parameters and symptoms support the physiological findings. This study shows that a high concentration of CO(2) in indoor air seem to be one parameter causing physiological effects, which can decrease the facility user's functional ability. The correct amount of ventilation with relation to the number of people using the facility, functional air distribution, and regular breaks can counteract the decrease in functional ability. The findings of the study suggest that merely increasing ventilation is not necessarily a rational solution from a technical-economical viewpoint. Instead or in addition, more comprehensive, anthropocentric planning of space is needed as well as instructions and new kinds of reference values for the design and realization of office environments. PMID- 26273787 TI - Investigation of NKX2.5 gene mutations in congenital heart defects in an Indian population. AB - BACKGROUND AND AIM: Mutations in the NKX2.5 gene, a cardiac transcription factor, have been implicated in various types of congenital heart defects (CHD) and it is known that optimal expression levels of this gene are crucial for proper cardiogenesis. However, most of the mutations have been identified in cases of syndromic CHD, and the functional significance of other mutations in this gene has not been studied. We describe in this study the mutational and expression analysis of the NKX2.5 gene in nonsyndromic CHD patients. METHODS: In this study, exon 1 of the NKX2.5 gene was sequenced from 50 probands with sporadic CHD and 50 healthy volunteers. NKX2.5 gene expression levels in blood and cardiac tissue samples were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) in the probands. RESULTS: No new mutations were identified; however, a previously reported variant A63G (rs2277923) was found to be present at significantly higher levels in the CHD population than in the control group. Changes in expression between the blood and tissue samples were seen in 37 out of the 50 CHD patients. CONCLUSION: Multiple factors, in addition to NKX2.5 gene mutations, may cause CHDs. NKX2.5 gene mutations may be mosaic in nature, therefore warranting investigation in both blood and tissue samples. PMID- 26273788 TI - Hepatic metabolism of carcinogenic beta-asarone. AB - beta-Asarone (1) belongs to the group of naturally occurring phenylpropenes like eugenol or anethole. Compound 1 is found in several plants, e.g., Acorus calamus or Asarum europaeum. Compound 1-containing plant materials and essential oils thereof are used to flavor foods and alcoholic beverages and as ingredients of many drugs in traditional phytomedicines. Although 1 has been claimed to have several positive pharmacological effects, it was found to be genotoxic and carcinogenic in rodents (liver and small intestine). The mechanism of action of carcinogenic allylic phenylpropenes consists of the metabolic activation via cytochrome P450 enzymes and sulfotransferases. In vivo experiments suggested that this pathway does not play a major role in the carcinogenicity of the propenylic compound 1 as is the case for other propenylic compounds, e.g., anethole. Since the metabolic pathways of 1 have not been investigated and its carcinogenic mode of action is unknown, we investigated the metabolism of 1 in liver microsomes of rats, bovines, porcines, and humans using (1)H NMR, HPLC-DAD, and LC-ESI-MS/MS techniques. We synthesized the majority of identified metabolites which were used as reference compounds for the quantification and final verification of metabolites. Microsomal epoxidation of the side chain of 1 presumably yielded (Z) asarone-1',2'-epoxide (8a) which instantly was hydrolyzed to the corresponding erythro- and threo-configurated diols (9b, 9a) and the ketone 2,4,5 trimethoxyphenylacetone (13). This was the main metabolic pathway in the metabolism of 1 in all investigated liver microsomes. Hydroxylation of the side chain of 1 led to the formation of three alcohols at total yields of less than 30%: 1'-hydroxyasarone (2), (E)- and (Z)-3'-hydroxyasarone (4 and 6), with 6 being the mainly formed alcohol and 2 being detectable only in liver microsomes of Aroclor 1254-pretreated rats. Small amounts of 4 and 6 were further oxidized to the corresponding carbonyl compounds (E)- and (Z)-3'-oxoasarone (5, 7). 1' Oxoasarone (3) was probably also formed in incubations with 1 but was not detectable, possibly due to its rapid reaction with nucleophiles. Eventually, three mono-O-demethylated metabolites of 1 were detected in minor concentrations. The time course of metabolite formation and determined kinetic parameters show little species-specific differences in the microsomal metabolism of 1. Furthermore, the kinetic parameters imply a very low dependence of the pattern of metabolite formation from substrate concentration. In human liver microsomes, 71 75% of 1 will be metabolized via epoxidation, 21-15% via hydroxylation (and further oxidation), and 8-10% via demethylation at lower as well as higher concentrations of 1, respectively (relative values). On the basis of our results, we hypothesize that the genotoxic epoxides of 1 are the ultimate carcinogens formed from 1. PMID- 26273789 TI - Magnetic resonance imaging as a tool to image neuroinflammation in a rat model of Parkinson's disease--phagocyte influx to the brain is promoted by bilberry enriched diet. AB - Neuroinflammation is a chronic event in neurodegenerative disorders. In the rat model of Parkinson's disease, including a striatal injection of the neurotoxin 6 hydroxydopamine (6-OHDA), antioxidant treatment affects the inflammatory process. Despite a heavy accumulation of microglia early after the injury, dopamine nerve fibre regeneration occurs. It remains unclear why this heavy accumulation of microglia is found early after the lesion in antioxidant-treated animals, or even more, what is the origin of these microglia. In this study magnetic resonance imaging (MRI) was used to elucidate whether the inflammatory response was generated from the blood or from activated brain microglia. Superparamagnetic iron oxide (SPIO) nanoparticles were injected intravenously prior to a striatal 6 OHDA injection to tag phagocytes in the blood. Rats were fed either with bilberry enriched or control diet. T2*-weighted MRI scans were performed 1 week after the lesion, and hypointense areas were calculated from T2*-weighted images, to monitor the presence of SPIO particles. The results revealed that feeding the animals with bilberries significantly promoted accumulation of blood-derived immune cells. Gadolinium-enhanced MRI demonstrated no difference in leakage of the blood-brain barrier independent of diets. To conclude, bilberry-enriched diet promotes an influx of periphery-derived immune cells to the brain early after injury. PMID- 26273790 TI - Diagnostic value of red blood cell distribution width in pediatric acute appendicitis. AB - BACKGROUND: The aim of this study was to evaluate the diagnostic value of red blood cell distribution width (RDW) in children with acute appendicitis. METHODS: In this retrospective study, a total of 344 children aged <=18 years with clinically suspected acute appendicitis who underwent appendectomy between January 2007 and January 2014 were reviewed, and 200 healthy controls of the same age group were included. Based on histopathology, the patients were classified as having normal appendix, simple or perforated appendicitis, and preoperative white blood cell count (WBC), C-reactive protein (CRP) and RDW were compared. RESULTS: Compared with the controls, mean WBC, CRP and RDW were significantly higher in the appendectomy group (P <0.001). The children with simple or perforated appendicitis had significantly higher WBC, CRP and RDW than did those with normal appendix (P <0.001). Mean WBC and CRP were significantly higher in the children with perforated appendicitis (P <0.001), but no statistically significant difference was found in RDW between the simple and perforated appendicitis groups (P = 0.081). CONCLUSIONS: Children with histologically proven acute appendicitis have higher RDW than children without appendicitis, but the diagnostic value of RDW was not superior to WBC or CRP in children with acute appendicitis. Although higher RDW may be valuable for aiding the diagnosis of acute appendicitis in children, it is not a useful marker for predicting perforated appendicitis. PMID- 26273792 TI - Mononuclear Nonheme Iron(III)-Iodosylarene and High-Valent Iron-Oxo Complexes in Olefin Epoxidation Reactions. AB - High-spin iron(III)-iodosylarene complexes are highly reactive in the epoxidation of olefins, in which epoxides are formed as the major products with high stereospecificity and enantioselectivity. The reactivity of the iron(III) iodosylarene intermediates is much greater than that of the corresponding iron(IV)-oxo complex in these reactions. The iron(III)-iodosylarene species-not high-valent iron(IV)-oxo and iron(V)-oxo species-are also shown to be the active oxidants in catalytic olefin epoxidation reactions. The present results are discussed in light of the long-standing controversy on the one oxidant versus multiple oxidants hypothesis in oxidation reactions. PMID- 26273791 TI - Effect of vitamin D3 treatment on endothelial function in obese adolescents. AB - BACKGROUND: Obesity in children is associated with vitamin D deficiency and endothelial dysfunction. It is not known if treatment with vitamin D improves endothelial function in obese adolescents. OBJECTIVE: This study aimed to determine whether treatment with vitamin D3 improves endothelial function in obese adolescents. METHODS: Nineteen obese adolescents, 13-18 years of age, with 25-hydroxy vitamin D (25[OH]D) levels <75 nmol L(-1) were treated with 100 000 IU vitamin D3 orally once a month for 3 months in an open-label, single-centre prospective trial. Endothelial function was assessed by flow-mediated dilatation (FMD) of the brachial artery at study entry and 1 month after the third dose of vitamin D3 . Biochemical parameters, including calcium, fasting lipids, glucose, insulin and high-sensitivity C-reactive protein, were also obtained. RESULTS: Mean 25(OH)D levels increased from 55.9 +/- 12.2 to 86.9 +/- 16.7 nmol L(-1) (P < 0.01). There was no correlation between 25(OH)D levels and brachial artery FMD. The brachial artery FMD (%) did not change significantly following vitamin D3 treatment (9.5 +/- 3.53 vs. 10.3 +/- 3.83, P = 0.83). Serum parathyroid hormone declined from 3.8 +/- 1.5 to 3.1 +/- 1 pmol L(-1) (P = 0.01). The remainder of biochemical measurements did not show a significant change. CONCLUSIONS: Treatment with vitamin D3 , 100 000 IU once a month for 3 months was effective in increasing 25(OH)D levels in obese adolescents but did not impact endothelial function. PMID- 26273793 TI - Medical Nutrition Therapy Is Effective in the Management of Hypoglycemia Caused by Insulin Antibodies: A Case Report and Literature Review. AB - Autoimmune antibodies, induced by exogenous insulin preparations, may result in labile glucose control and frequent hypoglycemia in some rare cases. In addition to insulin cessation, immune suppressants and/or plasmapheresis have been used as the primary remedies for these patients. Some previous studies also indicate that the condition tends to remit spontaneously after discontinuation of insulin exposure. Because of this, the clinical importance of nutritional interventions and behavioral approaches, which may play a role in ameliorating the symptoms, should also be emphasized. Herein, we report on a 64-year-old man with hypoglycemia induced by insulin antibodies (IAs), whose hypoglycemic symptoms significantly improved after the implementation of nutrition therapy. This rare case expands our knowledge of the management of hypoglycemia, and for the first time highlights the significance of nutritional and lifestyle intervention in treatment of IA-induced hypoglycemia. PMID- 26273794 TI - The Double-H Maze: A Robust Behavioral Test for Learning and Memory in Rodents. AB - Spatial cognition research in rodents typically employs the use of maze tasks, whose attributes vary from one maze to the next. These tasks vary by their behavioral flexibility and required memory duration, the number of goals and pathways, and also the overall task complexity. A confounding feature in many of these tasks is the lack of control over the strategy employed by the rodents to reach the goal, e.g., allocentric (declarative-like) or egocentric (procedural) based strategies. The double-H maze is a novel water-escape memory task that addresses this issue, by allowing the experimenter to direct the type of strategy learned during the training period. The double-H maze is a transparent device, which consists of a central alleyway with three arms protruding on both sides, along with an escape platform submerged at the extremity of one of these arms. Rats can be trained using an allocentric strategy by alternating the start position in the maze in an unpredictable manner (see protocol 1; S4.7), thus requiring them to learn the location of the platform based on the available allothetic cues. Alternatively, an egocentric learning strategy (protocol 2; S4.8) can be employed by releasing the rats from the same position during each trial, until they learn the procedural pattern required to reach the goal. This task has been proven to allow for the formation of stable memory traces. Memory can be probed following the training period in a misleading probe trial, in which the starting position for the rats alternates. Following an egocentric learning paradigm, rats typically resort to an allocentric-based strategy, but only when their initial view on the extra-maze cues differs markedly from their original position. This task is ideally suited to explore the effects of drugs/perturbations on allocentric/egocentric memory performance, as well as the interactions between these two memory systems. PMID- 26273795 TI - Structure of Echivulgarine, a Pyrrolizidine Alkaloid Isolated from the Pollen of Echium vulgare. AB - 1,2-Dehydropyrrolizidine alkaloids are common toxic metabolites isolated from plants within the Boraginaceae, in particular from the genera Heliotropium and Echium. Previous studies have deduced the structures of these often potent bioactives based upon mass spectrometric evidence, but these identifications have not established conclusive connectivity and configurational data. Herein, we describe the isolation and full structural characterization of echivulgarine, occurring in the pollen of Echium vulgare and correct the structure previously ascribed to the compound, using a comprehensive combination of both experimental and calculated nuclear magnetic resonance and electronic circular dichroism spectroscopic data. PMID- 26273797 TI - Erratum. AB - The Molecular Profile of Adult T-Cell Acute Lymphoblastic Leukemia: Mutations in RUNX1 and DNMT3A Are Associated with Poor Prognosis in T-ALL. Vera Grossmann, Claudia Haferlach, Sandra Weissmann, Andreas Roller, Sonja Schindela, Franziska Poetzinger, Kathrin Stadler, Frauke Bellos, Wolfgang Kern, Torsten Haferlach, Susanne Schnittger, and Alexander Kohlmann. Genes, Chromosomes & Cancer (2013) 52(4):410-422. DOI 10.1002/gcc.22039. For the above mentioned article, the authors submit a revised version of Figure 2A. The two protein domains MTase and PWWP of the DNMT3A protein were wrongly depicted in the legend, as the MTase domain has to be colored in green and PWWP in blue. The authors apologize to the editors of Genes, Chromosomes & Cancer and to the readers of this journal for this mistake. PMID- 26273796 TI - Correlative Confocal and 3D Electron Microscopy of a Specific Sensory Cell. AB - Delineation of a cell's ultrastructure is important for understanding its function. This can be a daunting project for rare cell types diffused throughout tissues made of diverse cell types, such as enteroendocrine cells of the intestinal epithelium. These gastrointestinal sensors of food and bacteria have been difficult to study because they are dispersed among other epithelial cells at a ratio of 1:1,000. Recently, transgenic reporter mice have been generated to identify enteroendocrine cells by means of fluorescence. One of those is the peptide YY-GFP mouse. Using this mouse, we developed a method to correlate confocal and serial block-face scanning electron microscopy. We named the method cocem3D and applied it to identify a specific enteroendocrine cell in tissue and unveil the cell's ultrastructure in 3D. The resolution of cocem3D is sufficient to identify organelles as small as secretory vesicles and to distinguish cell membranes for volume rendering. Cocem3D can be easily adapted to study the 3D ultrastructure of other specific cell types in their native tissue. PMID- 26273798 TI - Coffee and Caregiving. PMID- 26273800 TI - Therapeutic applications of the TAT-mediated protein transduction system for complex I deficiency and other mitochondrial diseases. AB - Among the five enzyme complexes in the oxidative phosphorylation system, NADH coenzyme Q oxidoreductase (also called complex I) is the largest, most intricate, and least understood. This enzyme complex spans the inner mitochondrial membrane and catalyzes the first step of electron transfer by the oxidation of NADH, and thereby provides two electrons for the reduction of quinone to quinol. Complex I deficiency is associated with many severe mitochondrial diseases, including Leber hereditary optic neuropathy and Leigh syndrome. However, to date, conventional treatments for the majority of genetic mitochondrial diseases are only palliative. Developing a reliable and convenient therapeutic approach is therefore considered to be an urgent need. Targeted proteins fused with the protein transduction domain of human immunodeficiency virus 1 transactivator of transcription (TAT) have been shown to enter cells by crossing plasma membranes while retaining their biological activities. Recent developments show that, in fusion with mitochondrial targeting sequences (MTSs), TAT-MTS-bound cargo can be correctly transported into mitochondria and restore the missing function of the cargo protein in patients' cells. The available evidence suggests that the TAT mediated protein transduction system holds great promise as a potential therapeutic approach to treat complex I deficiency, as well as other mitochondrial diseases. PMID- 26273801 TI - Synthesis of a diboryl-N-heterocycle and its conversion to a bidentate cationic Lewis acid. AB - Sequential reaction of 2-lithio-1-methylimidazole with 9-borabicyclo[3.3.1]nonane (9-BBN) dimer and 9-Cl-9-BBN yields diboryl-N-heterocycle C4H5N2(H)(BC8H14)2 (1). Reaction of 1 with I2 results in the net substitution of chelated hydride for a singly boron-bound iodide to produce C4H5N2(I)(BC8H14)2 (2). Conversely, reaction of 1 with [Ph3C][B(C6F5)4] results in the formation of the bidentate cationic Lewis acid [(C4H5N2)(BC8H14)2][B(C6F5)4] (3). Compound 3 catalyzes the hydrogenation of N-benzylidene-tert-butylamine at room-temperature. PMID- 26273802 TI - Determining the effects of freshwater inflow on benthic macrofauna in the Caloosahatchee Estuary, Florida. AB - Florida legislation requires determining and implementing an appropriate range and frequency of freshwater inflows that will sustain a fully functional estuary. Changes in inflow dynamics to the Caloosahatchee Estuary, Florida have altered salinity regimes that, in turn, have altered the ecological integrity of the estuary. The purpose of this current project is to determine how changes in freshwater inflows affect water quality, and in turn, benthic macrofauna, spatially within the Caloosahatchee Estuary and between multiyear wet and dry periods. Thirty-four benthic species were identified as being indicator species for salinity zones, and the estuary was divided into 4 zones based on differences in community structure within the estuary. Community structure had the highest correlations with water quality parameters that were common indicators of freshwater conditions resulting from inflows. A significant relationship between salinity and diversity occurs both spatially and temporally because of increased numbers of marine species as salinities increase. A salinity-based model was used to estimate inflow during wet and dry periods for each of the macrofauna community zones. The approach used here (identifying bioindicators and community zones with corresponding inflow ranges) is generic and will be useful for developing targets for managing inflow in estuaries worldwide. Integr Environ Assess Manag 2016;12:529-539. (c) 2015 SETAC. PMID- 26273804 TI - Newborn pulse oximetry screening is not just for heart defects. PMID- 26273799 TI - Corticosteroids for treating optic neuritis. AB - BACKGROUND: Optic neuritis is an inflammatory disease of the optic nerve. It usually presents with an abrupt loss of vision and recovery of vision is almost never complete. It occurs more commonly in women than in men. Closely linked in pathogenesis, optic neuritis may be the initial manifestation for multiple sclerosis. In some people, no underlying cause can be found. OBJECTIVES: The objective of this review was to assess the effects of corticosteroids on visual recovery in eyes with acute optic neuritis. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2015, Issue 4), MEDLINE (January 1950 to April 2015), EMBASE (January 1980 to April 2015), Latin American and Caribbean Health Sciences Literature (LILACS) (January 1982 to April 2015), PubMed (January 1946 to April 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The metaRegister of Controlled Trials (mRCT) was last searched on 6 March 2014. The electronic databases were last searched on 7 April 2015. We also searched reference lists of identified trial reports for additional trials. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that evaluated systemic corticosteroids, in any form, dose or route of administration, in people with acute optic neuritis. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included six RCTs with a total of 750 participants. Each trial was conducted in a different country: Denmark, Germany, India, Japan, UK, and United States. Additionally, we identified two ongoing trials not due to be completed until 2016. Among the six trials included in this review, we judged one to be at high risk of bias. The remaining five trials were judged to be at either low or uncertain risk of biases.Five trials compared only two intervention groups and one trial had a three-arm comparison of oral corticosteroids or intravenous corticosteroids with placebo. Of the five trials with only two intervention groups, two trials compared oral corticosteroids versus placebo, two trials compared intravenous corticosteroids with placebo, and one trial compared intravenous dexamethasone with intravenous methylprednisolone plus oral prednisolone.Three trials evaluating oral corticosteroids used varying doses of corticosteroids versus placebo. In the meta-analyses to assess visual acuity, the risk ratio (RR) was 1.00 (95% confidence interval (CI) 0.82 to 1.23; participants = 398) at one month; 0.92 (95% CI 0.77 to 1.11; participants = 355) at six months; and 0.93 (95% CI 0.70 to 1.24; participants = 368) at one year. In the meta-analyses of two trials evaluating corticosteroids with total dose greater than 3000 mg administered intravenously, the RR of normal visual acuity (defined as 20/20 Snellen fraction or equivalent) in the intravenous corticosteroids group compared with the placebo group was 1.05 (95% CI 0.88 to 1.26; participants = 346) at six months. The RR of contrast sensitivity in the normal range for the same comparison was 1.11 (95% CI 0.92 to 1.33; participants = 346) at six months follow-up. The RR of normal visual field for this comparison was 1.08 (95% CI 0.96 to 1.21; 346 participants) at six months; and 1.01 (95% CI 0.86 to 1.19; participants = 316) at one year. Four trials reported adverse events primarily related to gastrointestinal symptoms and sleep disturbance; one trial reported minor adverse event of acne. AUTHORS' CONCLUSIONS: There is no conclusive evidence of benefit in terms of recovery to normal visual acuity, visual field or contrast sensitivity six months after initiation with either intravenous or oral corticosteroids at the doses evaluated in trials included in this review. PMID- 26273805 TI - Antithymidylate resistance enables transgene selection and cell survival for T cells in the presence of 5-fluorouracil and antifolates. AB - Antithymidylates (AThy) constitute a class of drugs used in the treatment of cancers such as lung, colon, breast and pancreas. These drugs inhibit DNA synthesis by targeting the enzymes dihydrofolate reductase (DHFR) and/or thymidylate synthase (TYMS). AThys effectively inhibit cancer cells, and also inhibit T cells, preventing anticancer immunity, which might otherwise develop from AThy-induced cancer destruction. We establish that T cells expressing mutant DHFR--DHFR L22F, F31S (DHFR(FS))--and/or mutant TYMS--TYMS T51S, G52S (TYMS(SS)) effectively survive in toxic concentrations of AThys methotrexate, pemetrexed and 5-fluorouracil. Furthermore, we show that DHFR(FS) permitted rapid selection of an inducible suicide transgene in T cells. These findings demonstrate that AThy resistances prevent AThy cytotoxicity to T cells while permitting selection of important transgenes. This technological development could enhance in vitro and in vivo survival and selection of T-cell therapeutics being designed for a broad range of cancers. PMID- 26273807 TI - Screening Household Members of Acute Brucellosis Cases in Endemic Areas and Risk Factors for Brucellosis. AB - Early diagnosis and treatment of acute brucellosis cases were targeted by screening the household members of the index cases. We also aimed to describe the causal relations of brucellosis in an endemic region. A cross-sectional study was performed among household members (29 index cases, 113 household members). Brucellosis was diagnosed on the basis of clinical findings, serum agglutinin titer of >=1/160 in standard tube agglutination test (STA), or a positive blood culture. Index cases were defined as patients who had been admitted to the clinic on suspicion of brucellosis and then confirmed as brucellosis cases. The people who lived in the same house as the index cases were defined as household members. The risk factors for seropositivity were studied by multivariate analysis. Independent variables of gender, consuming fresh cheese, blood groups, dealing with husbandry, and contact with the placenta of infected animals were included to the model. Backward and forward selections were performed. Nineteen out of 113 (17%) screened individuals had agglutination titers >=1/160. The mean ages of index cases and household members were 43 years (standard deviation [SD] 18) and 29 years (SD 19), respectively. In multivariate analysis, consuming fresh cheese (odds ratio [OR]=3.1, confidence interval [CI] 1.07-9.68, p=0.049), blood group A (OR=2.6, CI 1.18-5.96, p=0.018), contact with the placenta of the infected animals (OR=3.7, CI 1.42-9.68, p=0.007), and age >30 years (OR=2.8, CI 1.25-6.51, p=0.13) were found to be associated with brucellosis. In univariate analysis, the individuals with blood group B were protected from brucella infection (p=0.013). In conclusion, screening of the people in brucellosis-endemic areas should be considered for early diagnosis and treatment. To our knowledge, blood groups were studied for the first time by this study. Higher prevalence of brucellosis among the individuals with blood group A and less prevalence among the individuals with blood group B should be considered for further studies on pathogenesis. PMID- 26273806 TI - Bartonella Osteomyelitis of the Acetabulum: Case Report and Review of the Literature. AB - INTRODUCTION: Bartonella henselae commonly involves the mononuclear phagocyte system (MPS), and its most common presentation is lymphadenitis. Rarely, it can cause isolated osteomyelitis. We present a case of a 3 year old with constitutional symptoms and new onset of limp. Previously reported cases of osteomyelitis due to B. henselae are also reviewed here, keeping the index case in mind. METHODS: We conducted a Medline search using MeSH subject headings Bartonella and osteomyelitis, limited to humans. RESULTS: The index case is a 3 year-old female who had a subacute presentation with new-onset leg pain and fever. Subsequent imaging demonstrated osteomyelitis of the acetabulum. Multiple diagnostic attempts were unsuccessful, and the patient did not respond to empiric therapy. Despite indeterminate serology, the diagnosis of Bartonella osteomyelitis was eventually confirmed by PCR on bone biopsy of the lesion. The literature search revealed 48 publications, which were reduced to 28 when limiting articles to the English language and the pediatric population. After a report of 36 pediatric cases in 2007, there have been an additional 12 pediatric cases since 1998. Generally, these patients had a subacute presentation with relatively mild constitutional symptoms. Most commonly, bone involvement occurred as osteolytic lesions of the axial skeleton. Of the total 48 cases reported, only four reported involvement of the axial skeleton. CONCLUSION: We present the first case, to our knowledge, of pediatric osteomyelitis of the pelvis due to B. henselae with indeterminate serologic and positive PCR results. Bartonella osteomyelitis should be included in the differential diagnosis when typical pathogens are not identified or if the patient is slow to respond to standard therapies. The sensitivity of tissue PCR for Bartonella osteomyelitis is now better than the current gold standard of serology, and new management guidelines may need to reflect this. PMID- 26273808 TI - Rapid Differentiation of Filariae in Unstained and Stained Paraffin-Embedded Sections by a High-Resolution Melting Analysis PCR Assay. AB - BACKGROUND: Apart from infection with human filariae, zoonotic filariasis also occurs worldwide, and the numbers of cases have been increasing steadily. Diagnosis of intact filariae in tissues or organs depends on histological identification. The morphology of parasites in tissue-embedded sections is poor and shows high levels of homoplasy. Thus, the use of morphological characteristics in taxonomic studies is difficult and may not allow a specific diagnosis. METHODS: Here we report the use of real-time PCR with high-resolution melting analysis (HRM) to detect and identify Brugia malayi, Brugia pahangi, Wuchereria bancrofti, and Dirofilaria immitis in paraffin-embedded sections. Assay specificity was determined using other tissue-dwelling parasites, Angiostrongylus cantonensis, Gnathostoma spinigerum, and Cysticercus cellulosae. We also developed a quick paraffin removal protocol. RESULTS: Both human and animal filariae in formalin-fixed paraffin-embedded sections (FFPES) were diagnosed and identified rapidly, whereas other parasites were negative. There was no difference in the melting temperature of products amplified from filarial DNA obtained from unstained FFPES and Hematoxylin & Eosin-stained sections. Therefore, the DNA extraction protocols developed in this study could be used for real-time PCR with HRM. CONCLUSIONS: We report the successful application of a HRM-PCR assay to differentiate four filarial parasites in FFPES, thus providing the pathologist with an effective alternative diagnostic procedure. Furthermore, the quick paraffin removal protocol developed could shorten the duration and number of steps required for paraffin removal using a standard protocol. PMID- 26273809 TI - Epidemic Spread of Usutu Virus in Southwest Germany in 2011 to 2013 and Monitoring of Wild Birds for Usutu and West Nile Viruses. AB - Mosquito-borne viruses are becoming an increasing threat for Europe. One of these viruses is Usutu virus (USUV), a single-stranded RNA virus belonging to the Japanese encephalitis virus group within the family Flaviviridae. Since the occurrence of USUV among wild birds in June, 2011, infected Blackbirds (Turdus merula) have frequently been found dead in southwest Germany, cumulating in a massive die-off. Moreover, other bird species (Strigiformes) in this region have been affected. In a first study, 209 of over 600 dead birds (wild birds and birds kept in aviaries) collected from 2011 to 2013 carried USUV, more than 88% of them Blackbirds. USUV had already been detected in 2010, one year before the epizooty, in a mosquito-based surveillance program in Germany. The main epidemic area of the USUV outbreak in wild birds in southwest Germany has been similar for the last three years. In a second study during 2011 to 2013, 902 live migratory and resident birds (representing 87 bird species belonging to 14 bird orders) from four different sampling sites were bled and tested serologically and by qPCR for West Nile virus (WNV) and USUV infections. No USUV or WNV genomes were detected. Some migratory birds (mainly long-distance migrants and some partial migrants) carried neutralizing antibodies against WNV as discriminated by USUV and WNV cross-neutralization tests. Only few resident birds showed relevant USUV-specific neutralizing antibodies. The occurrence of USUV in the Upper Rhine valley area of southwest Germany is a proof of principle for the incursion and spread of other arthropod-borne (arbo)-viruses along these routes. Therefore, monitoring studies in birds and mosquitoes for the presence of arboviruses in these areas are indispensable. PMID- 26273810 TI - Results of the Screening of Tick-Borne Encephalitis Virus Antibodies in Human Sera from Eight Districts Collected Two Decades Apart. AB - The sera from healthy individuals aged 10-59 years randomly selected from the general population during repeated cross-sectional surveys were stored at -20 degrees C at the serum bank of the National Institute of Public Health in Prague. The sera included in the present study were collected in the 1980s and in 2001 in eight districts of the Czech Republic. The proportional representation of the study localities was similar in both periods. The sera were uniformly distributed in 5-year age groups for 10- to 19-year-olds and in 10-year age groups for 20- to 59-year-olds. Males and females were nearly equally represented in both periods. Altogether 704 sera, 434 from the period 1978-1989 and 270 from 2001, were screened for antibodies against tick-borne encephalitis virus (TBEV) by the virus neutralization test. The seroprevalence rates were 11.5% in the 1980s and 26.3% in 2001. From the logistic regression model, it follows that the chance of detecting anti-TBEV antibodies was more than twice higher in 2001 than in 1978 1989 (odds ratio [OR]=2.22). The differences between males and females were not statistically significant, nor was sex-period interaction. The time trends in the seropositivity rates were similar in all age groups, with the exception of the 10 to 14-year-olds (p=0.914). The rate of seropositives in the age group 15-59 years increased 1.9 times, whereas that in the age group 10-14 years rose 5.1 times. In areas comparable to those where the study sera were collected, the average incidence rates of tick-borne encephalitis (TBE) per 100,000 population aged 10-59 increased significantly from 3.35 in 1978-1989 to 8.96 in 2001 (p<0.001). The age-specific antibody trends in adult age groups in both periods suggest that clinically manifest or inapparent TBE cases do not induce lifelong immunity, but they are likely to reflect the previous epidemiological situation. PMID- 26273811 TI - Recognizing the Role of Skunks in Human and Animal Rabies Exposures in the Southwest. AB - Rabies is arguably the most important viral zoonotic disease worldwide with an estimated 55,000 human deaths each year. Globally, dogs are the primary animals affected. In the United States, especially on the East Coast, raccoons and bats are the primary reservoir. However, in the southwestern United States, skunk and bat rabies play a large role. We describe the epidemiology and environmental risk factors associated with rabies in the US Southwest using exposure data for 2004 2012 from one Arizona county as a case study. Unlike other parts of the country, here bats and skunks are the most commonly collected positive animals (62% and 32%, respectively). Even though most of the positive animals were bats, human and domestic animal exposures were primarily a result of skunk interactions (58% and 50%, respectively). Consequently, the majority of exposures occur early in the year, January and February, when the majority of skunk pickups also occur. Using public health surveillance data, our study highlights the importance of recognizing the role of skunks in human and animal exposures in the southwestern United States. Consistent with a "One Health" approach, our data show how wildlife and domestic animal and human exposures are associated and informative to one another. PMID- 26273812 TI - Epidemiologic and Environmental Risk Factors of Rift Valley Fever in Southern Africa from 2008 to 2011. AB - BACKGROUND: Rift Valley fever (RVF) outbreaks have been associated with periods of widespread and above-normal rainfall over several months. Knowledge on the environmental factors influencing disease transmission dynamics has provided the basis for developing models to predict RVF outbreaks in Africa. From 2008 to 2011, South Africa experienced the worst wave of RVF outbreaks in almost 40 years. We investigated rainfall-associated environmental factors in southern Africa preceding these outbreaks. METHODS: RVF epizootic records obtained from the World Animal Health Information Database (WAHID), documenting livestock species affected, location, and time, were analyzed. Environmental variables including rainfall and satellite-derived normalized difference vegetation index (NDVI) data were collected and assessed in outbreak regions to understand the underlying drivers of the outbreaks. RESULTS: The predominant domestic vertebrate species affected in 2008 and 2009 were cattle, when outbreaks were concentrated in the eastern provinces of South Africa. In 2010 and 2011, outbreaks occurred in the interior and southern provinces affecting over 16,000 sheep. The highest number of cases occurred between January and April but epidemics occurred in different regions every year, moving from the northeast of South Africa toward the southwest with each progressing year. The outbreaks showed a pattern of increased rainfall preceding epizootics ranging from 9 to 152 days; however, NDVI and rainfall were less correlated with the start of the outbreaks than has been observed in eastern Africa. CONCLUSIONS: Analyses of the multiyear RVF outbreaks of 2008 to 2011 in South Africa indicated that rainfall, NDVI, and other environmental and geographical factors, such as land use, drainage, and topography, play a role in disease emergence. Current and future investigations into these factors will be able to contribute to improving spatial accuracy of models to map risk areas, allowing adequate time for preparation and prevention before an outbreak occurs. PMID- 26273813 TI - Coxiella burnetii (Q fever) Infection in Farmed Ruminants in Three Northeastern Provinces and Inner Mongolia Autonomous Region, China. AB - Coxiella burnetii is the pathogenic agent of Q fever, a zoonosis that occurs worldwide. In China, the organism infects people and a wide range of wild and farmed animals. However, little is known about C. burnetii infection in farmed ruminants in northeastern China, and there appears to have been no previous study on sika deer. The present study was conducted to determine the seroprevalence of C. burnetii in farmed ruminants in this region of China. A total of 3147 domestic ruminants (784 sheep, 1016 cattle, and 1347 sika deer) were randomly collected for this study. An indirect enzyme-linked immunosorbent assay kit was used to detect the antibodies to C. burnetii. The results showed an overall seroprevalence of 16.7% in domestic ruminants (24.9%, 13.5%, and 12.3% in cattle, sheep, and sika deer, respectively). This is the first report of C. burnetii seroprevalence in sika deer in China. Protective and hygiene measures should be applied in farm management to reduce the risk of exposure of C. burnetii to humans. PMID- 26273814 TI - Molecular Identification of Borrelia miyamotoi in Ixodes ricinus from Portugal. AB - Borrelia miyamotoi, a relapsing fever spirochete, has been found recently in Ixodes ricinus ticks; however, little is known about its spatial distribution and potential local impact on human health. A total of 640 ticks (447 nymphs and 193 adults) collected throughout Portugal were analyzed using two nested PCR protocols, one targeting the flagellin gene and the other the internal transcribed space region between the 5S and the 23S rRNA. As a result, B. miyamotoi was detected, for the first time, in one guesting I. ricinus nymph collected in the Lisboa district. In addition, a prevalence of 11% (71/640) for B. burgdorferi sensu lato was obtained. Even though no human relapsing fever cases due to infection by B. miyamotoi have been reported yet in Portugal, surveillance must be improved to provide better insight into the prevalence and distribution of this spirochete in ticks. PMID- 26273815 TI - Detection of Diverse Novel Bat Astrovirus Sequences in the Czech Republic. AB - Astroviruses are a major cause of gastroenteritis in humans and animals. Recently, novel groups of astroviruses were identified in apparently healthy insectivorous bats. We report the detection of diverse novel astrovirus sequences in nine different European bat species: Eptesicus serotinus, Hypsugo savii, Myotis emarginatus, M. mystacinus, Nyctalus noctula, Pipistrellus nathusii or P. pygmaeus, P. pipistrellus, Vespertilio murinus, and Rhinolophus hipposideros. In six bat species, astrovirus sequences were detected for the first time. One astrovirus strain detected in R. hipposideros clustered phylogenetically with Chinese astrovirus strains originating from bats of the families Rhinolophidae and Hipposideridae. All other Czech astrovirus sequences from vesper bats formed, together with one Hungarian sequence, a separate monophyletic lineage within the bat astrovirus group. These findings provide new insights into the molecular epidemiology, ecology, and prevalence of astroviruses in European bat populations. PMID- 26273816 TI - Detection of Cytomegalovirus in Patients with Inflammatory Bowel Disease: Where to Biopsy and How Many Biopsies? AB - BACKGROUND: The potential negative impact of cytomegalovirus (CMV) in ulcerative colitis (UC) and Crohn's disease (CD) warrants efforts to improve the yield of diagnostic techniques. METHODS: We retrospectively determined the optimal biopsy location and number from sixty-eight patients with inflammatory bowel disease (66% UC, 31% CD, and 3% inflammatory bowel disease-unclassified) with CMV disease between 2005 and 2011. Biopsies with endoscopic and histologic inflammation were analyzed by immunohistochemistry and/or in situ hybridization. The proportion of positive biopsies was determined, and using data from the 25th percentile, we assessed the number of biopsies required to achieve an 80% probability of a single positive biopsy. RESULTS: Of the patients with a diagnosis by immunohistochemistry and/or in situ hybridization, 27 of 61 (44%; 95% confidence interval, 32-57) were positive by hematoxylin and eosin, and 11 of 36 (31%; 95% confidence interval, 16-46) had systemic CMV by polymerase chain reaction. Of the patients with biopsies proximal and distal to the splenic flexure, 1 of 11 with UC and 4 of 8 with CD had a diagnosis limited to the right colon. Twenty percent of biopsies were positive by immunohistochemistry or in situ hybridization (20% in UC and 17% in CD). Eleven biopsies in UC and 16 in CD were required to achieve an 80% probability of a positive biopsy. CONCLUSIONS: Biopsy location and number are important considerations when assessing for CMV. We recommend a flexible sigmoidoscopy with 11 biopsies in UC and a colonoscopy with 16 biopsies in CD. PMID- 26273817 TI - Abnormal Liver Biochemistry Is Common in Pediatric Inflammatory Bowel Disease: Prevalence and Associations. AB - BACKGROUND: Liver enzymes (LEs) abnormalities associated with pediatric inflammatory bowel diseases (IBD) are understudied. We undertook to describe the development and associations of abnormal LEs in pediatric IBD. METHODS: We ascertained a cohort of 300 children with IBD and collected retrospective data. A Kaplan-Meier analysis determined the time to development of different thresholds of abnormal LEs. Associations between clinical variables and the development of abnormal LEs were determined. RESULTS: The probability of developing the first episode of abnormal LEs above the upper limit of normal (ULN) within 150 months was 58.1% (16.3% by 1 mo post-IBD diagnosis). There was a 6% prevalence of primary sclerosing cholangitis (PSC) or autoimmune sclerosing cholangitis (ASC) in this cohort. Of those diagnosed with PSC/ASC, 93% had persistent LE elevations at a threshold of >2* ULN, while those without PSC/ASC had a 4% probability of this abnormality. Elevated gamma glutamyltranspeptidase levels of 252 U/L had a 99% sensitivity and 71% specificity for PSC/ASC in IBD. After exclusion of patients with PSC/ASC, corticosteroids, antibiotics, and exclusive enteral nutrition demonstrated strongly positive associations with the first development of abnormal LEs >ULN (hazard ratio 2.1 [95% confidence interval, 1.3-3.3], hazard ratio 5.6 [95% confidence interval, 3.6-8.9], hazard ratio 4.2 [95% confidence interval, 1.6-11.3], respectively). CONCLUSIONS: Abnormal LEs are common in pediatric IBD and occur early. PSC/ASC is associated with persistently high LEs and gamma glutamyltranspeptidase levels >252 U/L. Children with IBD are at risk of elevated LEs if they require medications other than 5-ASA to induce IBD remission. PMID- 26273818 TI - Pancreatic Autoantibodies Against CUZD1 and GP2 Are Associated with Distinct Clinical Phenotypes of Crohn's Disease. AB - BACKGROUND: Inflammatory bowel disease (IBD) is characterized by a broad spectrum of clinical phenotypes with different outcomes. In the last decades, several IBD associated autoantibodies have been identified and investigated for their diagnostic relevance. Autoantibodies against the pancreatic glycoproteins (PAB) CUB and zona pellucida-like domains-containing protein 1 (CUZD1), and glycoprotein 2 (GP2) have been demonstrated to possess high specificity for the diagnosis of IBD. Although several studies have shown significant interrelations of anti-GP2 positivity with disease phenotype, associations of clinical phenotypes with anti-CUZD1 are still unknown. The aim was to identify the association of clinical phenotypes with anti-CUZD1 and anti-GP2 in a well-defined German IBD cohort. METHODS: Patients with IBD (224 patients with Crohn's disease and 136 patients with ulcerative colitis), who were tested for anti-GP2 and anti CUZD1 immunoglobulin G and immunoglobulin A by indirect immunofluorescence on transfected cells between 2005 and 2013, were included. Serotype and specified phenotypic data were collected in retrospect and statistically analyzed. RESULTS: Both anti-GP2 (P < 0.001) and anti-CUZD1 (P < 0.001) were significantly more prevalent in patients with Crohn's disease than in ulcerative colitis. PAB positivity was associated with ileocolonic disease (P = 0.002), perianal disease (P = 0.011), immunosuppressive treatment (P = 0.036), and ASCA positivity (P = 0.036). Anti-CUZD1 positivity was associated with ileocolonic (P = 0.016) and perianal disease (P = 0.002), whereas anti-GP2 positivity was positively associated with stricturing behavior (P = 0.016). CONCLUSIONS: We found distinct clinical phenotypes to be associated with PAB positivity. Therefore, determination of PABs and their subgroup analysis might identify patients with complicated disease behavior. However, the clinical relevance of our findings should be further evaluated in prospective cohorts. PMID- 26273819 TI - Acute severe organophosphate poisoning in a child who was successfully treated with therapeutic plasma exchange, high-volume hemodiafiltration, and lipid infusion. AB - Acute severe organophosphate poisoning is a serious complication seen in developing and agricultural countries. Pralidoxime and high dose atropine are the standard treatments. There is no consensus about acute severe organophosphate poisonings that are unresponsive to pralidoxime, atropine, and supportive therapies. We report a case of acute severe organophosphate poisoning that was unresponsive to standard treatments and successfully treated with high-volume continuous venovenous hemodiafiltration and therapeutic plasma exchange combined with lipid infusion. J. Clin. Apheresis 31:467-469, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26273820 TI - Acculturation and health behaviors among international students: A qualitative approach. AB - The process of acculturation often results in changes in the health behavior of international students. This study employed an open-ended, qualitative approach in an attempt to gain an in-depth understanding of the acculturation process for physical activity, diet, and drinking behavior among international students. Eighteen undergraduate international students (average age 19.20, standard deviation 1.21) were interviewed for 45-60 min. Most of the international students became more physically active after they arrived in the United States. Facilitators included accessibility, weight management, free time, and role modeling. Most international students were unsatisfied with the food on campus. Their strategies for adjusting to this included ordering food from restaurants, visiting supermarkets, and moving off campus. Most international students felt uncomfortable with the drinking culture in the United States, although some of them felt drinking was a good way to socialize with Americans and explore American culture. Colleges and universities should adopt strategies to better help their international students build lifelong healthy behaviors. PMID- 26273821 TI - Peptide-Modulated Self-Assembly of Chromophores toward Biomimetic Light Harvesting Nanoarchitectonics. AB - Elegant self-assembling complexes by the combination of proteins/peptides with functional chromophores are decisively responsible for highly efficient light harvesting and energy transfer in natural photosynthetic systems. Mimicking natural light-harvesting complexes through synthetic peptides is attractive due to their advantanges of programmable primary structure, tunable self-assembly architecture and easy availability in comparison to naturally occuring proteins. Here, an overview of recent progresses in the area of biomimetic light-harvesting nanoarchitectonics based on peptide-modulated self-assembly of chromophores is provided. Adjusting the organization of chromophores, either by creating peptide chromophore conjugates or by the non-covalent assembly of peptides and chromophores are highlighted. The light-harvesting properties, especially the energy transfer of the biomimetic complexes are critically discussed. The applications of such complexes in the mineralization of inorganic nanoparticles, generation of molecular hydrogen and oxygen, and photosynthesis of bioactive molecules are also included. PMID- 26273822 TI - The Time to Most Recent Common Ancestor Does Not (Usually) Approximate the Date of Divergence. AB - With the advent of more sophisticated models and increase in computational power, an ever-growing amount of information can be extracted from DNA sequence data. In particular, recent advances have allowed researchers to estimate the date of historical events for a group of interest including time to most recent common ancestor (TMRCA), dates of specific nodes in a phylogeny, and the date of divergence or speciation date. Here I use coalescent simulations and re-analyze an empirical dataset to illustrate the importance of taxon sampling, in particular, on correctly estimating such dates. I show that TMRCA of representatives of a single taxon is often not the same as divergence date due to issues such as incomplete lineage sorting. Of critical importance is when estimating divergence or speciation dates a representative from a different taxonomic lineage must be included in the analysis. Without considering these issues, studies may incorrectly estimate the times at which historical events occurred, which has profound impacts within both research and applied (e.g., those related to public health) settings. PMID- 26273823 TI - Correction: Association between Maternal Depression Symptoms across the First Eleven Years of Their Child's Life and Subsequent Offspring Suicidal Ideation. PMID- 26273824 TI - Short Pulse Duration High-Power Laser Photocoagulation during Vitrectomy for Diabetic Retinopathy Reduces Postoperative Inflammation. AB - The aim of this preliminary study was to determine the effectiveness of short pulse duration, high-power laser photocoagulation (PC) during vitrectomy for diabetic retinopathy (DR).The effects of short pulse duration PC with power of 340-360 mW and duration of 0.02 second were compared to conventional PC with power of 120-150 mW and duration of 0.2 second. The degree of inflammation was quantified by laser flare cell photometry before and at 1 day, 1 week, 4 week, and 12 weeks postoperatively. Twenty-two eyes of 22 consecutive patients were studied. Ten eyes were treated with short pulse duration PC and 12 eyes with conventional PC. The total energy was significantly lower in the short pulse duration PC group than in the conventional PC group (P = 0.007). The flare cell values were not significantly different between the two groups after 1 day, but at 1 week, the flare cell value was significantly lower in the short pulse duration PC group than in the conventional PC group (P = 0.04). This difference was also present at 4 and 12 weeks (P<0.05). The significant lower inflammation after short pulse duration PC than conventional PC indicates that the short pulse duration PC protocol should be considered to treat DR. PMID- 26273825 TI - An Anthropogenic Habitat Facilitates the Establishment of Non-Native Birds by Providing Underexploited Resources. AB - Anthropogenic modification of habitats may reduce the resources available for native species, leading to population declines and extinction. These same habitats often have the highest richness of non-native species. This pattern may be explained if recently human-modified habitats provide novel resources that are more accessible to non-native species than native species. Using non-native birds in the Iberian Peninsula as a case study, we conduct a large-scale study to investigate whether non-native species are positively associated with human modified habitats, and to investigate whether this positive association may be driven by the presence of resources that are not fully exploited by native species. We do this by comparing the functional diversity and resource use of native and non-native bird communities in a recently human-modified habitat (rice fields) and in more traditional habitats in the Iberian Peninsula. The functional diversity of native bird communities was lower in rice fields, but non-native birds were positively associated with rice fields and plugged this gap. Differences in resource use between native and non-native species allowed non native species to exploit resources that were plentiful in rice fields, supporting the role of underexploited resources in driving the positive association of non-native birds with rice fields. Our results provide a potential mechanism explaining the positive association of non-native species with anthropogenic habitats, and further work is needed to test if this applies more generally. PMID- 26273826 TI - ApiAP2 Factors as Candidate Regulators of Stochastic Commitment to Merozoite Production in Theileria annulata. AB - BACKGROUND: Differentiation of one life-cycle stage to the next is critical for survival and transmission of apicomplexan parasites. A number of studies have shown that stage differentiation is a stochastic process and is associated with a point that commits the cell to a change over in the pattern of gene expression. Studies on differentiation to merozoite production (merogony) in T. annulata postulated that commitment involves a concentration threshold of DNA binding proteins and an auto-regulatory loop. PRINCIPAL FINDINGS: In this study ApiAP2 DNA binding proteins that show changes in expression level during merogony of T. annulata have been identified. DNA motifs bound by orthologous domains in Plasmodium were found to be enriched in upstream regions of stage-regulated T. annulata genes and validated as targets for the T. annulata AP2 domains by electrophoretic mobility shift assay (EMSA). Two findings were of particular note: the gene in T. annulata encoding the orthologue of the ApiAP2 domain in the AP2-G factor that commits Plasmodium to gametocyte production, has an expression profile indicating involvement in transmission of T. annulata to the tick vector; genes encoding related domains that bind, or are predicted to bind, sequence motifs of the type 5'-(A)CACAC(A) are implicated in differential regulation of gene expression, with one gene (TA11145) likely to be preferentially up-regulated via auto-regulation as the cell progresses to merogony. CONCLUSIONS: We postulate that the Theileria factor possessing the AP2 domain orthologous to that of Plasmodium AP2-G may regulate gametocytogenesis in a similar manner to AP2-G. In addition, paralogous ApiAP2 factors that recognise 5'-(A)CACAC(A) type motifs could operate in a competitive manner to promote reversible progression towards the point that commits the cell to undergo merogony. Factors possessing AP2 domains that bind (or are predicted to bind) this motif are present in the vector borne genera Theileria, Babesia and Plasmodium, and other Apicomplexa; leading to the proposal that the mechanisms that control stage differentiation will show a degree of conservation. PMID- 26273827 TI - Increased Myeloid Cell Production and Lung Bacterial Clearance in Mice Exposed to Cigarette Smoke. AB - Pneumonia is a leading cause of hospitalization in patients with chronic obstructive pulmonary disease (COPD). Although most patients with COPD are smokers, the effects of cigarette smoke exposure on clearance of lung bacterial pathogens and on immune and inflammatory responses are incompletely defined. Here, clearance of Streptococcus pneumoniae and Pseudomonas aeruginosa and associated immune responses were examined in mice exposed to cigarette smoke or after smoking cessation. Mice exposed to cigarette smoke for 6 weeks or 4 months demonstrated decreased lung bacterial burden compared with air-exposed mice when infected 16 to 24 hours after exposure. When infection was performed after smoke cessation, bacterial clearance kinetics of mice previously exposed to smoke reversed to levels comparable to those of control mice, suggesting that the observed defects were not dependent on adaptive immunological memory to bacterial determinants found in smoke. Comparing cytokine levels and myeloid cell production before infection in mice exposed to cigarette smoke with mice never exposed or after smoke cessation revealed that reduced bacterial burden was most strongly associated with higher levels of IL-1beta and granulocyte-macrophage colony-stimulating factor in the lungs and with increased neutrophil reserve and monocyte turnover in the bone marrow. Using Serpinb1a-deficient mice with reduced neutrophil numbers and treatment with granulocyte colony-stimulating factor showed that increased neutrophil numbers contribute only in part to the effect of smoke on infection. Our findings indicate that cigarette smoke induces a temporary and reversible increase in clearance of lung pathogens, which correlates with local inflammation and increased myeloid cell output from the bone marrow. PMID- 26273828 TI - Pattern and Rate of Cognitive Decline in Cerebral Small Vessel Disease: A Prospective Study. AB - OBJECTIVES: Cognitive impairment, predominantly affecting processing speed and executive function, is an important consequence of cerebral small vessel disease (SVD). To date, few longitudinal studies of cognition in SVD have been conducted. We determined the pattern and rate of cognitive decline in SVD and used the results to determine sample size calculations for clinical trials of interventions reducing cognitive decline. METHODS: 121 patients with MRI confirmed lacunar stroke and leukoaraiosis were enrolled into the prospective St George's Cognition And Neuroimaging in Stroke (SCANS) study. Patients attended one baseline and three annual cognitive assessments providing 36 month follow-up data. Neuropsychological assessment comprised a battery of tests assessing working memory, long-term (episodic) memory, processing speed and executive function. We calculated annualized change in cognition for the 98 patients who completed at least two time-points. RESULTS: Task performance was heterogeneous, but significant cognitive decline was found for the executive function index (p<0.007). Working memory and processing speed decreased numerically, but not significantly. The executive function composite score would require the smallest samples sizes for a treatment trial with an aim of halting decline, but this would still require over 2,000 patients per arm to detect a 30% difference with power of 0.8 over a three year follow-up. CONCLUSIONS: The pattern of cognitive decline seen in SVD over three years is consistent with the pattern of impairments at baseline. Rates of decline were slow and sample sizes would need to be large for clinical trials aimed at halting decline beyond initial diagnosis using cognitive scores as an outcome measure. This emphasizes the importance of more sensitive surrogate markers in this disease. PMID- 26273829 TI - The Role of Cell Volume in the Dynamics of Seizure, Spreading Depression, and Anoxic Depolarization. AB - Cell volume changes are ubiquitous in normal and pathological activity of the brain. Nevertheless, we know little of how cell volume affects neuronal dynamics. We here performed the first detailed study of the effects of cell volume on neuronal dynamics. By incorporating cell swelling together with dynamic ion concentrations and oxygen supply into Hodgkin-Huxley type spiking dynamics, we demonstrate the spontaneous transition between epileptic seizure and spreading depression states as the cell swells and contracts in response to changes in osmotic pressure. Our use of volume as an order parameter further revealed a dynamical definition for the experimentally described physiological ceiling that separates seizure from spreading depression, as well as predicted a second ceiling that demarcates spreading depression from anoxic depolarization. Our model highlights the neuroprotective role of glial K buffering against seizures and spreading depression, and provides novel insights into anoxic depolarization and the relevant cell swelling during ischemia. We argue that the dynamics of seizures, spreading depression, and anoxic depolarization lie along a continuum of the repertoire of the neuron membrane that can be understood only when the dynamic ion concentrations, oxygen homeostasis,and cell swelling in response to osmotic pressure are taken into consideration. Our results demonstrate the feasibility of a unified framework for a wide range of neuronal behaviors that may be of substantial importance in the understanding of and potentially developing universal intervention strategies for these pathological states. PMID- 26273830 TI - Identification of Adverse Drug Events from Free Text Electronic Patient Records and Information in a Large Mental Health Case Register. AB - OBJECTIVES: Electronic healthcare records (EHRs) are a rich source of information, with huge potential for secondary research use. The aim of this study was to develop an application to identify instances of Adverse Drug Events (ADEs) from free text psychiatric EHRs. METHODS: We used the GATE Natural Language Processing (NLP) software to mine instances of ADEs from free text content within the Clinical Record Interactive Search (CRIS) system, a de identified psychiatric case register developed at the South London and Maudsley NHS Foundation Trust, UK. The tool was built around a set of four movement disorders (extrapyramidal side effects [EPSEs]) related to antipsychotic therapy and rules were then generalised such that the tool could be applied to additional ADEs. We report the frequencies of recorded EPSEs in patients diagnosed with a Severe Mental Illness (SMI) and then report performance in identifying eight other unrelated ADEs. RESULTS: The tool identified EPSEs with >0.85 precision and >0.86 recall during testing. Akathisia was found to be the most prevalent EPSE overall and occurred in the Asian ethnic group with a frequency of 8.13%. The tool performed well when applied to most of the non-EPSEs but least well when applied to rare conditions such as myocarditis, a condition that appears frequently in the text as a side effect warning to patients. CONCLUSIONS: The developed tool allows us to accurately identify instances of a potential ADE from psychiatric EHRs. As such, we were able to study the prevalence of ADEs within subgroups of patients stratified by SMI diagnosis, gender, age and ethnicity. In addition we demonstrated the generalisability of the application to other ADE types by producing a high precision rate on a non-EPSE related set of ADE containing documents. AVAILABILITY: The application can be found at http://git.brc.iop.kcl.ac.uk/rmallah/dystoniaml. PMID- 26273831 TI - Coaxial Electrospray of Ranibizumab-Loaded Microparticles for Sustained Release of Anti-VEGF Therapies. AB - Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness in people over age 65 in industrialized nations. Intravitreous injection of anti-VEGF (vascular endothelial growth factor) therapies, such as ranibizumab (trade name: Lucentis), provides an effective treatment option for neovascular AMD. We have developed an improved coaxial electrospray (CES) process to encapsulate ranibizumab in poly(lactic-co-glycolic) acid (PLGA) microparticles (MPs) for intravitreous injection and sustained drug release. This microencapsulation process is advantageous for maintaining the stability of the coaxial cone-jet configurations and producing drug-loaded MPs with as high as 70% encapsulation rate and minimal loss of bioactivitiy. The utility of this emerging process in intravitreous drug delivery has been demonstrated in both benchtop and in vivo experiments. The benchtop test simulates ocular drug release using PLGA MPs encapsulating a model drug. The in vivo experiment evaluates the inflammation and retinal cell death after intravitreal injection of the MPs in a chick model. The experimental results show that the drug-load MPs are able to facilitate sustained drug release for longer than one month. No significant long term microglia reaction or cell death is observed after intravitreal injection of 200 MUg MPs. The present study demonstrates the technical feasibility of using the improved CES process to encapsulate water-soluble drugs at a high concentration for sustained release of anti-VEGF therapy. PMID- 26273832 TI - Comprehensive Analysis of the 16p11.2 Deletion and Null Cntnap2 Mouse Models of Autism Spectrum Disorder. AB - Autism spectrum disorder comprises several neurodevelopmental conditions presenting symptoms in social communication and restricted, repetitive behaviors. A major roadblock for drug development for autism is the lack of robust behavioral signatures predictive of clinical efficacy. To address this issue, we further characterized, in a uniform and rigorous way, mouse models of autism that are of interest because of their construct validity and wide availability to the scientific community. We implemented a broad behavioral battery that included but was not restricted to core autism domains, with the goal of identifying robust, reliable phenotypes amenable for further testing. Here we describe comprehensive findings from two known mouse models of autism, obtained at different developmental stages, using a systematic behavioral test battery combining standard tests as well as novel, quantitative, computer-vision based systems. The first mouse model recapitulates a deletion in human chromosome 16p11.2, found in 1% of individuals with autism. The second mouse model harbors homozygous null mutations in Cntnap2, associated with autism and Pitt-Hopkins-like syndrome. Consistent with previous results, 16p11.2 heterozygous null mice, also known as Del(7Slx1b-Sept1)4Aam weighed less than wild type littermates displayed hyperactivity and no social deficits. Cntnap2 homozygous null mice were also hyperactive, froze less during testing, showed a mild gait phenotype and deficits in the three-chamber social preference test, although less robust than previously published. In the open field test with exposure to urine of an estrous female, however, the Cntnap2 null mice showed reduced vocalizations. In addition, Cntnap2 null mice performed slightly better in a cognitive procedural learning test. Although finding and replicating robust behavioral phenotypes in animal models is a challenging task, such functional readouts remain important in the development of therapeutics and we anticipate both our positive and negative findings will be utilized as a resource for the broader scientific community. PMID- 26273833 TI - Absence of Vitamin K-Dependent gamma-Carboxylation in Human Periostin Extracted from Fibrotic Lung or Secreted from a Cell Line Engineered to Optimize gamma Carboxylation. AB - Periostin (PN, gene name POSTN) is an extracellular matrix protein that is up regulated in bronchial epithelial cells and lung fibroblasts by TH-2 cytokines. Its paralog, TGF-beta-induced protein (betaig-h3, gene name TGFBI), is also expressed in the lung and up-regulated in bronchial myofibroblasts by TGF-beta. PN and betaig-h3 contain fasciclin 1 modules that harbor putative recognition sequences for gamma-glutamyl carboxylase and are annotated in UniProt as undergoing vitamin K-dependent gamma-carboxylation of multiple glutamic acid residues. gamma-carboxylation profoundly alters activities of other proteins subject to the modification, e.g., blood coagulation factors, and would be expected to alter the structure and function of PN and betaig-h3. To analyze for the presence of gamma-carboxylation, proteins extracted from fibrotic lung were reacted with monoclonal antibodies specific for PN, betaig-h3, or modification with gamma-carboxyglutamic acid (Gla). In Western blots of 1-dimensional gels, bands stained with anti-PN or -betaig-h3 did not match those stained with anti Gla. In 2-dimensional gels, anti-PN-positive spots had pIs of 7.0 to >8, as expected for the unmodified protein, and there was no overlap between anti-PN positive and anti-Gla-positive spots. Recombinant PN and blood coagulation factor VII were produced in HEK293 cells that had been transfected with vitamin K 2, 3 epoxide reductase C1 to optimize gamma-carboxylation. Recombinant PN secreted from these cells did not react with anti-Gla antibody and had pIs similar to that found in extracts of fibrotic lung whereas secreted factor VII reacted strongly with anti-Gla antibody. Over 67% coverage of recombinant PN was achieved by mass spectrometry, including peptides with 19 of the 24 glutamates considered targets of gamma-carboxylation, but analysis revealed no modification. Over 86% sequence coverage and three modified glutamic acid residues were identified in recombinant fVII. These data indicate that PN and betaig-h3 are not subject to vitamin K dependent gamma-carboxylation. PMID- 26273835 TI - Correction: Implications of the circumpolar genetic structure of polar bears for their conservation in a rapidly warming Arctic. PMID- 26273834 TI - Transcriptome Profiles of Human Lung Epithelial Cells A549 Interacting with Aspergillus fumigatus by RNA-Seq. AB - Lung epithelial cells constitute the first defense line of host against the inhaled Aspergillus fumigatus; however, the transcriptional response of human alveolar type II epithelial cells was still unclear. Here we used RNA-Seq technology to assess the transcriptome profiles of A549 cells following direct interaction with conidia of A. fumigatus. The total number of identified genes was 19118. Compared with uninfected A549 cells, 459 genes were differentially expressed in cells co-incubated with conidia for 8 h, including 302 up-regulated genes and 157 down-regulated genes. GO and KEGG pathway enrichment analysis showed that most of the up-regulated genes were related to immune response, chemotaxis and inflammatory response and enriched in cytokine-cytokine receptor interaction, JAK-STAT and MAPK signaling pathways. The down-regulated genes were mainly enriched for terms associated with development, hemopoiesis and ion transport. Among them, EGR4 and HIST1H4J gene had the maximum of fold change in up-regulated and down-regulated genes, respectively. Fourteen up-regulated genes and three down-regulated genes were further validated and significant increase on expression of IL-6, IL-8 and TNF-alpha in A549 cells were confirmed by qRT-PCR during the interaction of A549 cells with A. fumigatus. Besides, western blot showed that expression of two proteins (ARC, EGR1) significantly increased in A549 cells during interaction with A. fumigatus conidia for 8h. Interference of endogenous expression of ARC or EGR1 protein in A549 cells reduced the internalization of A. fumigatus. These results provided important insights into dynamic changes of gene expression in lung epithelial cells, especially its strong immunological response against A. fumigatus infection. PMID- 26273836 TI - Increases of Chamber Height and Base Diameter Have Contrasting Effects on Grazing Rate of Two Cladoceran Species: Implications for Microcosm Studies. AB - Aquatic microcosm studies often increase either chamber height or base diameter (to increase water volume) to test spatial ecology theories such as "scale" effects on ecological processes, but it is unclear whether the increase of chamber height or base diameter have the same effect on the processes, i.e., whether the effect of the shape of three-dimensional spaces is significant. We orthogonally manipulated chamber height and base diameter and determined swimming activity, average swimming velocity and grazing rates of the cladocerans Daphnia magna and Moina micrura (on two algae Scenedesmus quadricauda and Chlorella vulgaris; leading to four aquatic algae-cladoceran systems in total) under different microcosm conditions. Across all the four aquatic systems, increasing chamber height at a given base diameter significantly decreased the duration and velocity of horizontal swimming, and it tended to increase the duration but decrease the velocity of vertical swimming. These collectively led to decreases in both average swimming velocity and grazing rate of the cladocerans in the tall chambers (at a given base diameter), in accordance with the positive relationship between average swimming velocity and grazing rate. In contrast, an increase of base diameter at a given chamber height showed contrasting effects on the above parameters. Consistently, at a given chamber volume increasing ratio of chamber height to base diameter decreased the average swimming velocity and grazing rate across all the aquatic systems. In general, increasing chamber depth and base diameter may exert contrasting effects on zooplankton behavior and thus phytoplankton-zooplankton interactions. We suggest that spatial shape plays an important role in determining ecological process and thus should be considered in a theoretical framework of spatial ecology and also the physical setting of aquatic microcosm experiments. PMID- 26273837 TI - Optimal Sequence of Irinotecan and Oxaliplatin-Based Regimens in Metastatic Colorectal Cancer: A Population-Based Observational Study. AB - The optimal sequence of irinotecan and oxaliplatin-based regimens for metastatic colorectal cancer remains unclear. We conducted a population-based observational study by retrospectively reviewing records from Taiwan's National Health Insurance Research Database to explore this issue. Patients aged >= 20 years with metastatic colorectal cancer newly diagnosed between 2004 and 2008 (n = 9490) were enrolled in current study. Among these 9490 patients, 3895 patients (41.04%) did not receive any chemotherapy within the first three months after catastrophic illness registration. Patients who received best supportive care were older and had higher Charlson comorbidity indexes and incidences of comorbidities than those who received irinotecan-based regimens, oxaliplatin-based regimens, and 5 fluorouracil/capecitabine alone. Patients who received irinotecan followed by oxaliplatin-based regimens and those who received the reverse sequence were further stratified into arm A (n = 542) and arm B (n = 1156), respectively. The median first time to next treatment was not significantly different between arm A and arm B (210 days vs. 196 days; p = 0.17). However, the median second time to next treatment was longer in arm A than in arm B (155 days vs. 123 days; p = 0.006), which translated into a better overall survival (487 days vs. 454 days; p = 0.02). The crossover rate was higher in arm A than in arm B (47.84% vs. 41.61%; p<0.001). Multivariate Cox regression analyses showed that overall survival was comparable between the two chemotherapy sequences (p = 0.27). Our study suggested that irinotecan followed by oxaliplatin-based regimens might be a better chemotherapy treatment option for metastatic colorectal cancer than the reverse sequence given the higher crossover rate and potential overall survival benefit. PMID- 26273838 TI - Cleanroom Maintenance Significantly Reduces Abundance but Not Diversity of Indoor Microbiomes. AB - Cleanrooms have been considered microbially-reduced environments and are used to protect human health and industrial product assembly. However, recent analyses have deciphered a rather broad diversity of microbes in cleanrooms, whose origin as well as physiological status has not been fully understood. Here, we examined the input of intact microbial cells from a surrounding built environment into a spacecraft assembly cleanroom by applying a molecular viability assay based on propidium monoazide (PMA). The controlled cleanroom (CCR) was characterized by ~6.2*103 16S rRNA gene copies of intact bacterial cells per m2 floor surface, which only represented 1% of the total community that could be captured via molecular assays without viability marker. This was in contrast to the uncontrolled adjoining facility (UAF) that had 12 times more living bacteria. Regarding diversity measures retrieved from 16S rRNA Illumina-tag analyzes, we observed, however, only a minor drop in the cleanroom facility allowing the conclusion that the number but not the diversity of microbes is strongly affected by cleaning procedures. Network analyses allowed tracking a substantial input of living microbes to the cleanroom and a potential enrichment of survival specialists like bacterial spore formers and archaeal halophiles and mesophiles. Moreover, the cleanroom harbored a unique community including 11 exclusive genera, e.g., Haloferax and Sporosarcina, which are herein suggested as indicators of cleanroom environments. In sum, our findings provide evidence that archaea are alive in cleanrooms and that cleaning efforts and cleanroom maintenance substantially decrease the number but not the diversity of indoor microbiomes. PMID- 26273840 TI - Correction: Allogeneic Non-Adherent Bone Marrow Cells Facilitate Hematopoietic Recovery but Do Not Lead to Allogeneic Engraftment. PMID- 26273839 TI - Evaluating the Hypoxia Response of Ruffe and Flounder Gills by a Combined Proteome and Transcriptome Approach. AB - Hypoxia has gained ecological importance during the last decades, and it is the most dramatically increasing environmental factor in coastal areas and estuaries. The gills of fish are the prime target of hypoxia and other stresses. Here we have studied the impact of the exposure to hypoxia (1.5 mg O2/l for 48 h) on the protein expression of the gills of two estuarine fish species, the ruffe (Gymnocephalus cernua) and the European flounder (Platichthys flesus). First, we obtained the transcriptomes of mixed tissues (gills, heart and brain) from both species by Illumina next-generation sequencing. Then, the gill proteomes were investigated using two-dimensional gel electrophoresis and mass spectrometry. Quantification of the normalized proteome maps resulted in a total of 148 spots in the ruffe, of which 28 (18.8%) were significantly regulated (> 1.5-fold). In the flounder, 121 spots were found, of which 27 (22.3%) proteins were significantly regulated. The transcriptomes were used for the identification of these proteins, which was successful for 15 proteins of the ruffe and 14 of the flounder. The ruffe transcriptome dataset comprised 87,169,850 reads, resulting in an assembly of 72,108 contigs (N50 = 1,828 bp). 20,860 contigs (26.93%) had blastx hits with E < 1e-5 in the human sequences in the RefSeq database, representing 14,771 unique accession numbers. The flounder transcriptome with 78,943,030 reads assembled into 49,241 contigs (N50 = 2,106 bp). 20,127 contigs (40.87%) had a hit with human proteins, corresponding to 14,455 unique accession numbers. The regulation of selected genes was confirmed by quantitative real-time RT-PCR. Most of the regulated proteins that were identified by this approach function in the energy metabolism, while others are involved in the immune response, cell signalling and the cytoskeleton. PMID- 26273841 TI - Spatio-Temporal Dynamics of Hypoxia during Radiotherapy. AB - Tumour hypoxia plays a pivotal role in cancer therapy for most therapeutic approaches from radiotherapy to immunotherapy. The detailed and accurate knowledge of the oxygen distribution in a tumour is necessary in order to determine the right treatment strategy. Still, due to the limited spatial and temporal resolution of imaging methods as well as lacking fundamental understanding of internal oxygenation dynamics in tumours, the precise oxygen distribution map is rarely available for treatment planing. We employ an agent based in silico tumour spheroid model in order to study the complex, localized and fast oxygen dynamics in tumour micro-regions which are induced by radiotherapy. A lattice-free, 3D, agent-based approach for cell representation is coupled with a high-resolution diffusion solver that includes a tissue density dependent diffusion coefficient. This allows us to assess the space- and time resolved reoxygenation response of a small subvolume of tumour tissue in response to radiotherapy. In response to irradiation the tumour nodule exhibits characteristic reoxygenation and re-depletion dynamics which we resolve with high spatio-temporal resolution. The reoxygenation follows specific timings, which should be respected in treatment in order to maximise the use of the oxygen enhancement effects. Oxygen dynamics within the tumour create windows of opportunity for the use of adjuvant chemotherapeutica and hypoxia-activated drugs. Overall, we show that by using modelling it is possible to follow the oxygenation dynamics beyond common resolution limits and predict beneficial strategies for therapy and in vitro verification. Models of cell cycle and oxygen dynamics in tumours should in the future be combined with imaging techniques, to allow for a systematic experimental study of possible improved schedules and to ultimately extend the reach of oxygenation monitoring available in clinical treatment. PMID- 26273842 TI - HPLC Measurement of the DNA Oxidation Biomarker, 8-oxo-7,8-dihydro-2' deoxyguanosine, in Cultured Cells and Animal Tissues. AB - Oxidative stress is associated with many physiological and pathological processes, as well as xenobiotic metabolism, leading to the oxidation of biomacromolecules, including DNA. Therefore, efficient detection of DNA oxidation is important for a variety of research disciplines, including medicine and toxicology. A common biomarker of oxidatively damaged DNA is 8-oxo-7,8-dihydro-2' deoxyguanosine (8-oxo-dGuo; often erroneously referred to as 8-hydroxy-2' deoxyguanosine (8-OH-dGuo or 8-oxo-dG)). Several protocols for 8-oxo-dGuo measurement by high pressure liquid chromatography with electrochemical detection (HPLC-ED) have been described. However, these were mainly applied to purified DNA treated with pro-oxidants. In addition, due to methodological differences between laboratories, mainly due to differences in analytical equipment, the adoption of published methods for detection of 8-oxo-dGuo by HPLC-ED requires careful optimization by each laboratory. A comprehensive protocol, describing such an optimization process, is lacking. Here, a detailed protocol is described for the detection of 8-oxo-dGuo by HPLC-ED, in DNA from cultured cells or animal tissues. It illustrates how DNA sample preparation can be easily and rapidly optimized to minimize undesirable DNA oxidation that can occur during sample preparation. This protocol shows how to detect 8-oxo-dGuo in cultured human alveolar adenocarcinoma cells (i.e., A549 cells) treated with the oxidizing agent KBrO3, and from the spleen of mice exposed to the polycyclic aromatic hydrocarbon dibenzo(def,p)chrysene (DBC, formerly known as dibenzo(a,l)pyrene, DalP). Overall, this work illustrates how an HPLC-ED methodology can be readily optimized for the detection of 8-oxo-dGuo in biological samples. PMID- 26273844 TI - Custom-made Microdialysis Probe Design. AB - Microdialysis is a commonly used technique in neuroscience research. Therefore commercial probes are in great demand to monitor physiological, pharmacological and pathological changes in cerebrospinal fluid. Unfortunately, commercial probes are expensive for research groups in public institutions. In this work, a probe assembly is explained in detail to build a reliable, concentric, custom-made microdialysis probe for less than $10. The microdialysis probe consists of a polysulfone membrane with a molecular cut-off of 30 kDa. Probe in vitro recoveries of substances with different molecular weight (in the range of 100 1,600 Da) and different physicochemical properties are compared. The probe yields an in vitro recovery of approximately 20% for the small compounds glucose, lactate, acetylcholine and ATP. In vitro recoveries for neuropeptides with a molecular weight between 1,000-1,600 Da amount to 2-6%. Thus, while the higher molecular weight of the neuropeptides lowered in vitro recovery values, dialysis of compounds in the lower range (up to 500 Da) of molecular weights has no great impact on the in vitro recovery rate. The present method allows utilization of a dialysis membrane with other cut-off value and membrane material. Therefore, this custom-made probe assembly has the advantage of sufficient flexibility to dialyze substances in a broad molecular weight range. Here, we introduce a microdialysis probe with an exchange length of 2 mm, which is applicable for microdialysis in mouse and rat brain regions. However, dimensions of the probe can easily be adapted for larger exchange lengths to be used in larger animals. PMID- 26273843 TI - Bio-Conjugated CNT-Bridged 3D Porous Graphene Oxide Membrane for Highly Efficient Disinfection of Pathogenic Bacteria and Removal of Toxic Metals from Water. AB - More than a billion people lack access to safe drinking water that is free from pathogenic bacteria and toxic metals. The World Health Organization estimates several million people, mostly children, die every year due to the lack of good quality water. Driven by this need, we report the development of PGLa antimicrobial peptide and glutathione conjugated carbon nanotube (CNT) bridged three-dimensional (3D) porous graphene oxide membrane, which can be used for highly efficient disinfection of Escherichia coli O157:H7 bacteria and removal of As(III), As(V), and Pb(II) from water. Reported results demonstrate that versatile membrane has the capability to capture and completely disinfect pathogenic pathogenic E. coli O157:H7 bacteria from water. Experimentally observed disinfection data indicate that the PGLa attached membrane can dramatically enhance the possibility of destroying pathogenic E. coli bacteria via synergistic mechanism. Reported results show that glutathione attached CNT bridged 3D graphene oxide membrane can be used to remove As(III), As(V), and Pb(II) from water sample at 10 ppm level. Our data demonstrated that PGLa and glutathione attached membrane has the capability for high efficient removal of E. coli O157:H7 bacteria, As(III), As(V), and Pb(II) simultaneously from Mississippi River water. PMID- 26273845 TI - Iridium(III) Luminescent Probe for Detection of the Malarial Protein Biomarker Histidine Rich Protein-II. AB - This work outlines the synthesis of a non-emissive, cyclometalated Ir(III) complex, Ir(ppy)2(H2O)2(+) (Ir1), which elicits a rapid, long-lived phosphorescent signal when coordinated to a histidine-containing protein immobilized on the surface of a magnetic particle. Synthesis of Ir1, in high yields,is complete O/N and involves splitting of the parent cyclometalated Ir(III) chloro-bridged dimer into two equivalents of the solvated complex. To confirm specificity, several amino acids were probed for coordination activity when added to the synthesized probe, and only histidine elicited a signal response. Using BNT-II, a branched peptide mimic of the malarial biomarker Histidine Rich Protein II (pfHRP-II), the iridium probe was validated as a tool for HRP-II detection. Quenching effects were noted in the BNT-II/Ir1 titration when compared to L-Histidine/Ir1, but these were attributed to steric hindrance and triplet state quenching. Biolayer interferometry was used to determine real time kinetics of interaction of Ir1 with BNT-II. Once the system was optimized, the limit of detection of rcHRP-II using the probe was found to be 12.8 nM in solution. When this protein was immobilized on the surface of a 50 um magnetic agarose particle, the limit of detection was 14.5 nM. The robust signal response of this inorganic probe, as well as its flexibility of use in solution or immobilized on a surface, can lend itself toward a variety of applications, from diagnostic use to imaging. PMID- 26273846 TI - Influence of the menstrual cycle on breast skin elasticity. PMID- 26273847 TI - Simultaneous Electrophysiological Recording and Micro-injections of Inhibitory Agents in the Rodent Brain. AB - Here we describe a method for the construction of a single-use "injectrode" using commercially accessible and affordable parts. A probing system was developed that allows for the injection of a drug while recording electrophysiological signals from the affected neuronal population. This method provides a simple and economical alternative to commercial solutions. A glass pipette was modified by combining it with a hypodermic needle and a silver filament. The injectrode is attached to commercial microsyringe pump for drug delivery. This results in a technique that provides real-time pharmacodynamics feedback through multi-unit extracellular signals originating from the site of drug delivery. As a proof of concept, we recorded neuronal activity from the superior colliculus elicited by flashes of light in rats, concomitantly with delivery of drugs through the injectrode. The injectrode recording capacity permits the functional characterization of the injection site favoring precise control over the localization of drug delivery. Application of this method also extends far beyond what is demonstrated here, as the choice of chemical substance loaded into the injectrode is vast, including tracing markers for anatomic experiments. PMID- 26273848 TI - [Eustachian Tube Dilatation for Treatment of its Chronic Dysfunction]. PMID- 26273849 TI - Bone Conditioned Medium: Preparation and Bioassay. AB - Autologous bone grafts are widely used in oral and maxillofacial surgery, orthopedics, and traumatology. Autologous bone grafts not only replace missing bone, they also support the complex process of bone regeneration. This favorable behavior of autografts is attributed to the three characteristics: osteoconductivity, osteogenicity, and osteoinductivity. However, there is another aspect: Bone grafts release a myriad of molecules, including growth factors, which can target mesenchymal cells involved in bone regeneration. The paracrine properties of bone grafts can be studied in vitro by the use of bone-conditioned medium (BCM). Here we present a protocol on how to prepare bone-conditioned medium from native pig cortical bone, and bone that underwent thermal processing or demineralization. Cells can be directly exposed to BCM or seeded onto biomaterials, such as collagen membranes, previously soaked with BCM. We give examples for in vitro bioassays with mesenchymal cells on the expression of TGF beta regulated genes. The presented protocols should encourage to further reveal the paracrine effects of bone grafts during bone regeneration and open a path for translational research in the broad field of reconstructive surgery. PMID- 26273850 TI - Preparation of Highly Porous Coordination Polymer Coatings on Macroporous Polymer Monoliths for Enhanced Enrichment of Phosphopeptides. AB - We describe a protocol for the preparation of hybrid materials based on highly porous coordination polymer coatings on the internal surface of macroporous polymer monoliths. The developed approach is based on the preparation of a macroporous polymer containing carboxylic acid functional groups and the subsequent step-by-step solution-based controlled growth of a layer of a porous coordination polymer on the surface of the pores of the polymer monolith. The prepared metal-organic polymer hybrid has a high specific micropore surface area. The amount of iron(III) sites is enhanced through metal-organic coordination on the surface of the pores of the functional polymer support. The increase of metal sites is related to the number of iterations of the coating process. The developed preparation scheme is easily adapted to a capillary column format. The functional porous polymer is prepared as a self-contained single-block porous monolith within the capillary, yielding a flow-through separation device with excellent flow permeability and modest back-pressure. The metal-organic polymer hybrid column showed excellent performance for the enrichment of phosphopeptides from digested proteins and their subsequent detection using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The presented experimental protocol is highly versatile, and can be easily implemented to different organic polymer supports and coatings with a plethora of porous coordination polymers and metal-organic frameworks for multiple purification and/or separation applications. PMID- 26273851 TI - Characterization of process air emissions in automotive production plants. AB - During manufacturing, particles produced from industrial processes become airborne. These airborne emissions represent a challenge from an industrial hygiene and environmental standpoint. A study was undertaken to characterize the particles associated with a variety of manufacturing processes found in the auto industry. Air particulates were collected in five automotive plants covering ten manufacturing processes in the areas of casting, machining, heat treatment and assembly. Collection procedures provided information on air concentration, size distribution, and chemical composition of the airborne particulate matter for each process and insight into the physical and chemical processes that created those particles. PMID- 26273852 TI - Eyewitness memory: The impact of a negative mood during encoding and/or retrieval upon recall of a non-emotive event. AB - The police often appeal for eyewitnesses to events that were unlikely to have been emotive when observed. An eyewitness, however, may be in a negative mood whilst encoding or retrieving such events as mood can be influenced by a range of personal, social, and environmental factors. For example, bad weather can induce a negative mood. This experiment compared the impact of negative and neutral moods during encoding and/or retrieval upon eyewitness recall of a non-emotive event. A negative mood during encoding had no impact upon the number of correct details recalled (provided participants were in a neutral mood at retrieval) but a negative mood during retrieval impaired the number of correct details recalled (provided participants were in a neutral mood at encoding). A negative mood at both time points enhanced the number of correct details recalled, demonstrating a mood-dependent memory enhancement. The forensic implications of these findings are discussed. PMID- 26273853 TI - Early diagnosis is critical to ensure good outcomes in HIV-infected children: outlining barriers to care. AB - HIV-infected children require early initiation of antiretroviral therapy (ART) to ensure good outcomes. The aim was to investigate missed opportunities in childhood HIV diagnosis leading to delayed ART initiation. Baseline data were reviewed of all children aged <15 years referred over a 1-year period for ART initiation to the Kalafong Hospital HIV services in Gauteng, South Africa. Of the 250 children, one-quarter (24.5%) was of school-going age, 34.5% in the preschool group, 18% between 6 and 12 months old and 23% below 6 months of age (median age = 1.5 years [interquartile range 0.5-4.8]). Most children (82%) presented with advanced/severe HIV disease, particularly those aged 6-12 months (95%). Malnutrition was prominent and referrals were mostly from hospital inpatient services (61%). A structured caregiver interview was conducted in a subgroup, with detailed review of medical records and HIV results. The majority (>=89%) of the 65 interviewed caregivers reported good access to routine healthcare, except for postnatal care (26%). Maternal HIV-testing was mostly done during the second and third pregnancy trimesters (69%). Maternal non-disclosure of HIV status was common (63%) and 83% of mothers reported a lack of psychosocial support. Routine infant HIV-testing was not done in 66%, and inadequate reporting on patient-held records (Road-to-Health Cards/Booklets) occurred frequently (74%). Children with symptomatic HIV disease were not investigated at primary healthcare in 53%, and in 68% of families the siblings were not tested. One-third of children (35%) had a previous HIV diagnosis, with 77% of caregivers aware of these prior results, while 50% acknowledged failing to attend ART services despite referral. In conclusion, a clear strategy on paediatric HIV case finding, especially at primary healthcare, is vital. Multiple barriers need to be overcome in the HIV care pathway to reach high uptake of services, of which especially maternal reasons for not attending paediatric ART services need further exploration. PMID- 26273854 TI - Accurate Modeling of Organic Molecular Crystals by Dispersion-Corrected Density Functional Tight Binding (DFTB). AB - The ambitious goal of organic crystal structure prediction challenges theoretical methods regarding their accuracy and efficiency. Dispersion-corrected density functional theory (DFT-D) in principle is applicable, but the computational demands, for example, to compute a huge number of polymorphs, are too high. Here, we demonstrate that this task can be carried out by a dispersion-corrected density functional tight binding (DFTB) method. The semiempirical Hamiltonian with the D3 correction can accurately and efficiently model both solid- and gas phase inter- and intramolecular interactions at a speed up of 2 orders of magnitude compared to DFT-D. The mean absolute deviations for interaction (lattice) energies for various databases are typically 2-3 kcal/mol (10-20%), that is, only about two times larger than those for DFT-D. For zero-point phonon energies, small deviations of <0.5 kcal/mol compared to DFT-D are obtained. PMID- 26273855 TI - How Is C-H Vibrational Energy Redistributed in F + CHD3(nu1 = 1) -> HF + CD3? AB - The effects of CH stretching excitation on the F + CHD3 -> HF + CD3 reaction are studied experimentally using crossed-beam and time-sliced velocity map imaging techniques at the collision energy of 9.0 kcal/mol. The fraction of the vibrationally excited CHD3 reagent in the crossed-beam region was determined accurately, allowing us to investigate quantitatively the effects of CH stretching excitation on the title reaction. Experimental data show that the vibrational energy in the excited CH bond of CHD3 is almost exclusively deposited into the HF product vibration, and hence, the HF products from the excited-state reaction are about one vibrational quantum hotter than those of the ground-state reaction, while the vibrational state distribution of the CD3 products is only slightly affected. The reaction is suppressed by the CH stretching excitation, and the overall reactivity of the vibrationally excited reaction is 74 +/- 4% of that of the ground-state reaction for CD3(nu2 = 0, 1, 2, 3) product channels. PMID- 26273856 TI - Imidazolium Ionic Liquid Helps to Disperse Fullerenes in Water. AB - Light fullerenes attract significant interest in pharmacy and medicine as drug vectors and antioxidants and to block AIDS virus enzyme. The progress of these applications is hindered by poor solubility of fullerenes in aqueous media. We propose a highly efficient hydrophilic system to disperse the C60 fullerene based on the accurate atomistic-resolution computer simulations. The introduced system is based on 1-butyl-3-methylimidazolium tetrafluoroborate, [C4C1IM][BF4]-water mixtures. The first component is used to form a corona around C60 while exhibiting a significant miscibility with water. Structural and dynamical peculiarities of the C60-[C4C1IM][BF4]-water mixtures are discussed. PMID- 26273857 TI - Relative Stability of the La and Lb Excited States in Adenine and Guanine: Direct Evidence from TD-DFT Calculations of MCD Spectra. AB - The relative position of La and Lb pipi* electronic states in purine nucleobases is a much debated topic, since it can strongly affect our understanding of their photoexcited dynamics. To assess this point, we calculated the absorption and magnetic circular dichroism (MCD) spectra of adenine, guanine, and their nucleosides in gas-phase and aqueous solution, exploiting recent developments in MCD computational technology within time-dependent density functional theory. MCD spectroscopy allows us to resolve the intense S0-> La transition from the weak S0 > Lb transition. The spectra obtained in water solution, by using B3LYP and CAM B3LYP functionals and describing solvent effect by cluster models and by the polarizable continuum model (PCM), are in very good agreement with the experimental counterparts, thus providing direct and unambiguous evidence that the energy ordering predicted by TD-DFT, La < Lb, is the correct one. PMID- 26273858 TI - Dynamical Localization Limiting the Coherent Transport Range of Excitons in Organic Crystals. AB - Exciton or energy transport in organic crystals is commonly described by a series of incoherent hoppings. This picture is no longer valid if the transport range is on the order of the exciton coherent (or delocalization) size. However, coherent effects are often neglected because the exciton wave function generally localizes to a few molecules within an ultrafast time scale (<1 ps) after photoexcitation. Here, by using time-resolved photoemission spectroscopy and nanometer-thick zinc phthalocyanine crystals, we are able to observe a transition from the coherent to incoherent transport regime while the exciton coherent size is decreasing as a function of time. During the transition, a distinct phonon mode is excited, which suggests that the electron-vibrational interaction localizes the exciton and reduces its coherent size. It is anticipated that the coherent transport range can be increased by controlling the electron-vibrational coupling. An enhanced coherent transport range can be advantageous in applications such as organic photovoltaics. PMID- 26273859 TI - First-Principles Design of Hydrogen Dissociation Catalysts Based on Isoelectronic Metal Solid Solutions. AB - We report an innovative route for designing novel functional alloys based on first-principles calculations, which is an isoelectronic solid solution (ISS) of two metal elements to create new characteristics that are not native to the constituent elements. Neither Rh nor Ag exhibits hydrogen storage properties, whereas the Rh50Ag50 ISS exhibits properties similar to Pd; furthermore, Au cannot dissociate H2, and Ir has a higher energy barrier for the H2 dissociation reaction than Pt, whereas the Ir50Au50 ISS can dissociate H2 in a similar way to Pt. In the periodic table, Pd is located between Rh and Ag, and Pt is located between Ir and Au, leading to similar atomic and electronic structures between the pure metals (Pd and Pt) and the ISS alloys (Rh50Ag50 and Ir50Au50). From a practical perspective, the Ir-Au ISS would be more cost-effective to use than pure Pt, and could exhibit catalytic activity equivalent to Pt. Therefore, the Ir50Au50 ISS alloy can be a potential catalyst candidate for the replacement of Pt. PMID- 26273860 TI - Evolution of Hydrogen-Bond Networks in Protonated Water Clusters H(+)(H2O)n (n = 1 to 120) Studied by Cryogenic Ion Mobility-Mass Spectrometry. AB - Cryogenic (80 K) ion mobility-mass spectrometry (cryo-IM-MS) is employed to study structural transitions of protonated water clusters in both the small, H(+)(H2O)n (n = 1 to 30), and large, (n = 31 to ~120), size regions. In agreement with previous studies, we find compelling evidence of regions of uniform cluster decay in the small size region, accompanied by sharp transition points whereby the loss of a single water monomer induces a different H-bonding motif. The investigation of the isomeric distribution of each species at 80 K reveals experimental evidence supporting the notion that H(+)(H2O)n (n = 6) is the smallest system to possess both Eigen- (H3O(+)) and Zundel- (H5O2(+)) centered structures. Cryo-IM MS is particularly well-suited for studying clusters in the large size region, for which previous spectroscopic experimental studies are scarce. PMID- 26273861 TI - Gate Control of the Conduction Mechanism Transition from Tunneling to Thermally Activated Hopping. AB - We explore gate control of electron transport through molecules with different repeat units. In the framework of reduced density matrix theory, the computational results show (i) exponential decay in the tunneling regime and (ii) Arrhenius behavior and similar activation energies in the hopping regime, which are qualitatively consistent with experimental observations. Moreover, the gate enables tuning of the activation energy, indicating that the continuous transition from tunneling to hopping could be experimentally observed. The activation energy-gate voltage characteristics are introduced to investigate different conduction regimes. PMID- 26273862 TI - Single-Layer Graphene as an Effective Mediator of the Metal-Support Interaction. AB - Single-layer chemical vapor deposition (CVD)-grown graphene was transferred onto a ZnO (0001) substrate forming a large-area, low-defect density, protective layer. The quality of the graphene layer and its effect on the interaction between the ZnO support and vapor-deposited cobalt particles was investigated by spectroscopic and microscopic techniques. We demonstrate that the in-between graphene layer influences both the oxidation state and the morphology of cobalt upon annealing in vacuum. In particular, cobalt strongly interacts with the bare ZnO substrate forming flat particles, which are readily oxidized and redispersed upon annealing in ultrahigh vacuum conditions. In contrast, in the presence of the graphene interlayer, cobalt forms highly dispersed nanoparticles, which are resistant to oxidation, but prone to surface diffusion and agglomeration. The graphene layer exhibits remarkable stability upon cobalt deposition and vacuum annealing, while interaction with reactive gases can facilitate the formation of defects. PMID- 26273863 TI - Observing the Hydration Layer of Trehalose with a Linked Molecular Terahertz Probe. AB - The terahertz (THz) absorption bands of biomolecular hydration layers are generally swamped by absorption from bulk water. Using the disaccharide trehalose, we show that this limitation can be overcome by attaching a molecular probe. By time-resolving the fluorescence shift of the probe, a local THz spectrum is obtained. From the dependence on temperature and H2O/D2O exchange, it is concluded that the trehalose hydration layer is being observed. The region of dynamic water perturbation by the disaccharide encompasses the probe and is therefore larger than the first two solvation layers. PMID- 26273864 TI - Chirality Synchronization in Trifluoroethanol Dimer Revisited: The Missing Heterochiral Dimer. AB - Chirality self-recognition in the dimer of transient chiral 2,2,2 trifluoroethanol (TFE) is studied using chirped pulse and cavity-based Fourier transform microwave spectroscopy with the aid of ab initio calculations. The broad-band and extreme high-resolution capabilities enable us to assign rotational spectra of the most stable homo- and heterochiral dimers and analyze their structural and dynamical properties in detail. A strong preference for the homochiral over the heterochiral diastereomers is observed. The current study unambiguously identifies the structure of the most stable homochiral dimer and supports the identification by the previous low-resolution infrared study. More importantly, it also indisputably detects the so far elusive, most stable heterochiral dimer. PMID- 26273865 TI - Effects of Exciton Polarity in Charge-Transfer Polymer/PCBM Bulk Heterojunction Films. AB - Charge-transfer copolymers with local electron density gradients, systematically modified by quantity and position of fluorination, result in widely variable (2 8%) power conversion efficiencies (PCEs). Ultrafast, near-infrared, transient absorption spectroscopy on the corresponding films reveals the influence of exciton polarity on ultrafast populations and decay dynamics for the charge separated and charge-transfer states as well as their strong correlation to device PCEs. By using an excitation energy-dependent, dynamic red shift in the transient absorption signal for the polymer cation, the exciton polarity induced by push-pull interactions within each polymer fragment is shown to enhance charge dissociation on time scales of tens to hundreds of picoseconds after excitation. These results suggest the important role played by the local electronic structure not only for exciton dissociation but also for device performance. PMID- 26273866 TI - In Search of Aggregation Pathways of IAPP and Other Amyloidogenic Proteins: Finding Answers through NMR Spectroscopy. AB - The deposition of aggregates of human islet amyloid peptide (hIAPP) has been correlated with the death of insulin-producing beta (beta) cells in type II diabetes mellitus. The actual molecular mechanism of cell death remains unknown; however, it has been postulated that the process of aggregation and amyloid fibril growth from monomeric hIAPP is closely involved. Intermediate IAPP aggregates are highly toxic to islet cells, but lack of structural knowledge of these oligomers and complications in applying biophysical techniques to their study have been the main obstacles in designing structure-based therapeutics. Furthermore, the involvement of metal ions (Cu(2+) and Zn(2+)) associated with hIAPP has demonstrated an effect on the aggregation pathway. In the absence of well-defined targets, research attempting to attenuate amyloid-linked toxicity has been substantially slowed. Therefore, obtaining high-resolution structural insights on these intermediates through NMR techniques can provide information on preventing IAPP aggregation. In this Perspective, a review of avenues to obtain fundamental new insights into the aggregation pathway of IAPP and other amyloidogenic proteins through NMR and other techniques is presented. PMID- 26273867 TI - Fast Recovery of the High Work Function of Tungsten and Molybdenum Oxides via Microwave Exposure for Efficient Organic Photovoltaics. AB - In this work, we use microwave exposure of tungsten and molybdenum oxides to improve hole extraction in organic photovoltaics (OPVs). This is a result of fast recovery of the high work function of metal oxides occurring within a few seconds of microwave processing. Using the space-charge-limited current model, we verified the formation of an anode contact that facilitates hole extraction, while Mott-Schottky analysis revealed the enhancement of the device built-in field in the devices with the microwave-exposed metal oxides. Both were attributed to the formation of large interfacial dipoles at the ITO/microwave exposed metal oxide interface. The power conversion efficiency (PCE) of OPVs using microwave-exposed metal oxides and based on blends of poly[(9-(1 octylnonyl)-9H-carbazole-2,7-diyl)-2,5-thiophenediyl-2,1,3-benzothiadiazole-4,7 diyl-2,5-thiophenediyl] (PCDTBT) with ([6,6]-phenyl-C71 butyric acid methyl ester, PC71BM) reached values of 7.2%, which represents an increase of about 30% compared with the efficiency of 5.7% of devices using metal oxides not subjected to microwave exposure. PMID- 26273869 TI - Building Force Fields: An Automatic, Systematic, and Reproducible Approach. AB - The development of accurate molecular mechanics force fields is a significant challenge that must be addressed for the continued success of molecular simulation. We developed the ForceBalance method to automatically derive accurate force field parameters using flexible combinations of experimental and theoretical reference data. The method is demonstrated in the parametrization of two rigid water models, yielding new parameter sets (TIP3P-FB and TIP4P-FB) that accurately describe many physical properties of water. PMID- 26273868 TI - Triple Guest Occupancy and Negative Compressibility in Hydrogen-Loaded beta Hydroquinone Clathrate. AB - The molecular interactions and structural behavior of a previously unexplored clathrate system, hydrogen-loaded beta-hydroquinone (beta-HQ+H2), were investigated under high pressure with synchrotron X-ray diffraction and Raman/infrared spectroscopies. The beta-HQ+H2 system exhibits coupling of two independently rare phenomena: multiple occupancy and negative compressibility. The number of H2 molecules per cavity increases from one to three, causing unit cell volume increase by way of unique crystallographic interstitial guest positioning. We anticipate these occupancy-derived trends may be general to a range of inclusion compounds and may aid the chemical and crystallographic design of both high-occupancy hydrogen storage clathrates and novel, variable composition materials with tunable mechanical properties. PMID- 26273870 TI - Heteroepitaxial Junction in Au-ZnSe Nanostructure: Experiment versus First Principle Simulation. AB - Composing together the experimental as well as the simulated results, we demonstrate here the atomic placements and the electronic structure at the epitaxial junction of a solution-processed heteronanostructure Au-ZnSe. Despite the large lattice mismatch (~32%) between fcc Au and zinc-blende structured ZnSe, the heterostructures are formed via coincidence site epitaxy, which appears periodically because of the arrangements of their proper unit cell placements at the junction. This reduces the interface energy and drives the formation of such heteronanostructures. Details of the physical processes involved in the formation of these nanostructures have been discussed in this letter, and epitaxy at the heterojunction is strongly supported by HRTEM measurement and DFT calculation. This material has the possibility of plasmon-exciton coupling and therefore might be a futuristic material for utilizations in catalysis, nanoelectronics, and other related applications. PMID- 26273871 TI - Simulations of Protein Aggregation: Insights from Atomistic and Coarse-Grained Models. AB - This Perspective highlights recent computational approaches to protein aggregation, from coarse-grained models to atomistic simulations, using the islet amyloid polypeptide (IAPP) as a case study. We review salient open questions where simulations can make an impact, discuss the successes and challenges met by simulations, and explore new directions. PMID- 26273872 TI - Photocatalysis from Fluorescence-Quenched CdSe/Au Nanoheterostructures: A Size Dependent Study. AB - We report a systematic study of the electron-transfer process from CdSe quantum dots (QDs) to the Au tips as a function of the QD diameter and also the size of the Au-tip. For Au-tips smaller than ~3 nm, that is, when they are still not metallic, a reduction in PL behavior is observed as the excited electrons are transferred from the QD-conduction band to Au, with quenching being higher for larger tips and smaller QDs. A combination of steady state and time-resolved studies establish the mechanism of charge transfer that is further confirmed by dye-degradation studies, showing the possibility of ambient day light photocatalysis. PMID- 26273873 TI - Photothermal Microscopy of Nonluminescent Single Particles Enabled by Optical Microresonators. AB - A powerful new paradigm for single-particle microscopy on nonluminescent targets is reported using ultrahigh-quality factor optical microresonators as the critical detecting element. The approach is photothermal in nature as the microresonators are used to detect heat dissipated from individual photoexcited nano-objects. The method potentially satisfies an outstanding need for single particle microscopy on nonluminescent objects of increasingly smaller absorption cross section. Simultaneously, our approach couples the sensitivity of label-free detection using optical microresonators with a means of deriving chemical information on the target species, a significant benefit. As a demonstration, individual nonphotoluminescent multiwalled carbon nanotubes are spatially mapped, and the per-atom absorption cross section is determined. Finite-element simulations are employed to model the relevant thermal processes and elucidate the sensing mechanism. Finally, a direct pathway to the extension of this new technique to molecules is laid out, leading to a potent new method of performing measurements on individual molecules. PMID- 26273874 TI - Radiation-Induced Nucleation of Diamond from Amorphous Carbon: Effect of Hydrogen. AB - Electron irradiation of anthracite functionalized by dodecyl groups leads to recrystallization of the carbon network into diamonds. The diamonds range in size from ~2 to ~10 nm and exhibit {111} spacing of 2.1 A. A bulk process consistent with bias-enhanced nucleation is proposed in which the dodecyl group provides hydrogen during electron irradiation. Recrystallization into diamond occurs in the hydrogenated graphitic subsurface layers. Unfunctionalized anthracite could not be converted into diamond during electron irradiation. The dependence of the phase transition pressure on cluster size was estimated, and it was found that diamond particles with a radius up to 20 nm could be formed. PMID- 26273875 TI - Reactivity of Carbon Dioxide on Nickel: Role of CO in the Competing Interplay between Oxygen and Graphene. AB - The catalytic conversion of carbon dioxide to synthetic fuels and other valuable chemicals is an issue of global environmental and economic impact. In this report we show by means of X-ray photoelectron spectroscopy in the millibar range that, on a Ni surface, the reduction of carbon dioxide is indirectly governed by the CO chemistry. While the growth of graphene and the carbide-graphene conversion can be controlled by selecting the reaction temperature, oxygen is mainly removed by CO, since oxygen reduction by hydrogen is a slow process on Ni. Even though there is still a consistent pressure gap with respect to industrial reaction conditions, the observed phenomena provide a plausible interpretation of the behavior of Ni/Cu based catalysts for CO2 conversion and account for a possible role of CO in the methanol synthesis process. PMID- 26273876 TI - Fast Computation of Solvation Free Energies with Molecular Density Functional Theory: Thermodynamic-Ensemble Partial Molar Volume Corrections. AB - Molecular density functional theory (MDFT) offers an efficient implicit-solvent method to estimate molecule solvation free-energies, whereas conserving a fully molecular representation of the solvent. Even within a second-order approximation for the free-energy functional, the so-called homogeneous reference fluid approximation, we show that the hydration free-energies computed for a data set of 500 organic compounds are of similar quality as those obtained from molecular dynamics free-energy perturbation simulations, with a computer cost reduced by 2 3 orders of magnitude. This requires to introduce the proper partial volume correction to transform the results from the grand canonical to the isobaric isotherm ensemble that is pertinent to experiments. We show that this correction can be extended to 3D-RISM calculations, giving a sound theoretical justification to empirical partial molar volume corrections that have been proposed recently. PMID- 26273877 TI - Highly Reversible Room-Temperature Sulfur/Long-Chain Sodium Polysulfide Batteries. AB - In a room-temperature sodium-sulfur (RT Na-S) battery, the complicated reduction reaction of the sulfur cathode generally involves two main steps: (i) transformation of elemental sulfur into long-chain soluble sodium polysulfides (Na2Sn 4 <= n <= 8) and (ii) conversion of the long-chain sodium polysulfides into solid-state short-chain polysulfide Na2S2 or disulfide Na2S. It is found that the slow kinetics of the second step limits the efficiency of discharge and induces irreversible capacity loss during cycling. Accordingly, we present here a RT Na-S cell operated with the sulfur/long-chain sodium polysulfide redox couple to avoid the capacity fade. An advanced cathode structure has been developed by inserting a carbon nanofoam interlayer between the sulfur cathode and the separator to localize the soluble polysulfide species and prevent its migration to the anode. The highly reversible sulfur/long-chain sodium polysulfide cell presented here can provide a stable output energy density of 450 Wh kg(-1) at an extremely low energy cost of ~$10 kWh(-1) (based on the active material of anode and cathode). PMID- 26273878 TI - Protection of p(+)-n-Si Photoanodes by Sputter-Deposited Ir/IrOx Thin Films. AB - Sputter deposition of Ir/IrOx on p(+)-n-Si without interfacial corrosion protection layers yielded photoanodes capable of efficient water oxidation (OER) in acidic media (1 M H2SO4). Stability of at least 18 h was shown by chronoamperomety at 1.23 V versus RHE (reversible hydrogen electrode) under 38.6 mW/cm(2) simulated sunlight irradiation (lambda > 635 nm, AM 1.5G) and measurements with quartz crystal microbalances. Films exceeding a thickness of 4 nm were shown to be highly active though metastable due to an amorphous character. By contrast, 2 nm IrOx films were stable, enabling OER at a current density of 1 mA/cm(2) at 1.05 V vs. RHE. Further improvement by heat treatment resulted in a cathodic shift of 40 mV and enabled a current density of 10 mA/cm(2) (requirements for a 10% efficient tandem device) at 1.12 V vs. RHS under irradiation. Thus, the simple IrOx/Ir/p(+)-n-Si structures not only provide the necessary overpotential for OER at realistic device current, but also harvest ~100 mV of free energy (voltage) which makes them among the best-performing Si based photoanodes in low-pH media. PMID- 26273879 TI - Electron-Hole Recombination Time at TiO2 Single-Crystal Surfaces: Influence of Surface Band Bending. AB - Photocatalytic activity is determined by the transport property of photoexcited carriers from the interior to the surface of photocatalysts. Because the carrier dynamics is influenced by a space charge layer (SCL) in the subsurface region, an understanding of the effect of the potential barrier of the SCL on the carrier behavior is essential. Here we have investigated the relaxation time of the photoexcited carriers on single-crystal anatase and rutile TiO2 surfaces by time resolved photoelectron spectroscopy and found that carrier recombination, taking a nanosecond time scale at room temperature, is strongly influenced by the barrier height of the SCL. Under the flat-band condition, which is realized in nanometer-sized photocatalysts, the carriers have a longer lifetime on the anatase surface than the rutile one, naturally explaining the higher photocatalytic activity for anatase than rutile. PMID- 26273880 TI - Is Nitrate Anion Photodissociation Mediated by Singlet-Triplet Absorption? AB - Photolysis of the nitrate anion is involved in the oxidation processes in the hydrosphere, cryosphere, and stratosphere. While it is known that the nitrate photolysis in the long-wavelength region proceeds with a very low quantum yield, the mechanism of the photodissociation remains elusive. Here, we present the quantitative modeling of singlet-singlet and singlet-triplet absorption spectra in the atmospherically relevant region around 300 nm, and we argue that a spin forbidden transition between the singlet ground state and the first triplet state contributes non-negligibly to the nitrate anion photolysis. We further propose that the nitrate anion excited into the first singlet excited state relaxes nonradiatively into its ground state. The full understanding of the nitrate anion photolysis can improve modeling of the asymmetric solvation in the atmospheric processes, e.g., photolysis on the surfaces of ice or snow. PMID- 26273881 TI - Vibrational Activation of Methane Chemisorption: The Role of Symmetry. AB - Quantum state-resolved reactivity measurements probe the role of vibrational symmetry on the vibrational activation of the dissociative chemisorption of CH4 on Pt(111). IR-IR double resonance excitation in a molecular beam is used to prepare CH4 in all three different vibrational symmetry components A1, E, and F2 of the 2nu3 antisymmetric stretch overtone vibration. Methyl dissociation products chemisorbed on the cold Pt(111) surface are detected via reflection absorption infrared spectroscopy (RAIRS). We observe similar reactivity for CH4 prepared in the A1 and F2 sublevels but up to a factor of 2 lower reactivity for excitation of the E sublevel. It is suggested that differences in the localization of the C-H stretch amplitudes for the three states at the transition state leads to the observed difference in reactivity rather than state-specific vibrational energy transfer to electronic excitation of the metal. PMID- 26273882 TI - Thermal Decoupling of Molecular-Relaxation Processes from the Vibrational Density of States at Terahertz Frequencies in Supercooled Hydrogen-Bonded Liquids. AB - At terahertz frequencies, the libration-vibration motions couple to the dielectric relaxations in disordered hydrogen-bonded solids. The interplay between these processes is still poorly understood, in particular at temperatures below the glass transition temperature, Tg, yet this behavior is of vital importance for the molecular mobility of such materials to remain in the amorphous phase. A series of polyhydric alcohols were studied at temperatures between 80 and 310 K in the frequency range of 0.2-3 THz using terahertz time domain spectroscopy. Three universal features were observed in the dielectric losses, epsilon"(nu): (a) At temperatures well below the glass transition, epsilon"(nu) comprises a temperature-independent microscopic peak, which persists into the liquid phase and which is identified as being due to librational/torsional modes. For 0.65 Tg < T < Tg, additional thermally dependent contributions are observed, and we found strong evidence for its relation to the Johari-Goldstein secondary beta-relaxation process. (b) Clear spectroscopic evidence is found for a secondary beta glass transition at 0.65 Tg, which is not related to the fragility of the glasses. (c) At temperatures above Tg, the losses become dominated by primary alpha-relaxation processes. Our results show that the thermal changes in the losses seem to be underpinned by a universal change in the hydrogen bonding structure of the samples. PMID- 26273883 TI - Computationally Efficient Prediction of Ionic Liquid Properties. AB - Due to fundamental differences, room-temperature ionic liquids (RTIL) are significantly more viscous than conventional molecular liquids and require long simulation times. At the same time, RTILs remain in the liquid state over a much broader temperature range than the ordinary liquids. We exploit the ability of RTILs to stay liquid at several hundred degrees Celsius and introduce a straightforward and computationally efficient method for predicting RTIL properties at ambient temperature. RTILs do not alter phase behavior at 600-800 K. Therefore, their properties can be smoothly extrapolated down to ambient temperatures. We numerically prove the validity of the proposed concept for density and ionic diffusion of four different RTILs. This simple method enhances the computational efficiency of the existing simulation approaches as applied to RTILs by more than an order of magnitude. PMID- 26273884 TI - High-Performance Li-S Batteries with an Ultra-lightweight MWCNT-Coated Separator. AB - A bifunctional separator consisting of a layer of multiwall carbon nanotubes (MWCNTs) on the cathode-side of a Celgard polypropylene sheet has been investigated to overcome the challenges of Li-S cells. The conductive/porous MWCNT-coating functions (i) as an upper current collector to facilitate electron transport and high active-material utilization and (ii) as a filter to intercept/absorb the migrating polysulfides and thereby suppress the polysulfide diffusion. Also, the access to the electrolyte through the porous network of MWCNT along with its fast electronic transport facilitates the reutilization of the trapped active material and superior long-term cyclability. The MWCNT-coating is lightweight (0.17 mg cm(-2)), yet allows the successful use of regular sulfur cathodes (high sulfur content of 70 wt %) with high discharge capacity, excellent rate performance, and long cycle life, demonstrating that the MWCNT-coated separator is a viable solution to practical Li-S batteries. PMID- 26273885 TI - Energy-Dependent UV Photodissociation of Gas-Phase Adenosine Monophosphate Nucleotide Ions: The Role of a Single Solvent Molecule. AB - The photodissociation of gaseous protonated adenosine 5'-monophosphate (AMP) and the same system hydrated with one water molecule has been investigated in the 4 to 13 eV photon energy range by coupling a linear quadrupole ion trap with a synchrotron radiation beamline. The dissociation of the bare AMP cation upon absorption of a single ultraviolet (UV) photon below the ionization energy (IE) almost exclusively produces the protonated adenine base, with a measured photodissociation yield showing spectroscopic features with dominant absorption bands located at 4.75 and 6.5 eV, found in agreement with TD-DFT calculations. Nevertheless, the addition of a single water molecule to the system modifies the dissociation energy dependence and strongly suppresses the cleavage of the glycosidic CN bond below the IE. Both the experimental and theoretical results suggest that a single solvent molecule can intrinsically influence the structure and physicochemical properties of the AMP cation, including its UV induced dissociation pattern, beyond the simple water evaporation. PMID- 26273886 TI - Ultrafast Charge Generation in an Organic Bilayer Film. AB - The dynamics of charge generation in a high performing molecular photovoltaic system, p-SIDT(FBTTh2)2 (see Figure 1 ) is studied with transient absorption. The optimized bulk heterojunction material shows behavior observed in many other systems; the majority of charges are generated at short time scales (<150 fs), and a slower contribution from incoherently diffusing excitons is observed at low pump fluence. In a separate experiment, the role of bulk heterojunction material morphology on the process of ultrafast charge generation was investigated with bilayers made with solution processed donor molecules on a photopolymerized C60 layer. The majority of carriers are again produced at short time scales, ruling out the idea that subpicosecond charge generation can be understood wholly in terms of localized excitons. We evaluate possible causes of this behavior and propose that the excited state is highly delocalized on short time scales, providing ample probability density at the charge generating interface. PMID- 26273887 TI - Mapping Li(+) Concentration and Transport via In Situ Confocal Raman Microscopy. AB - We demonstrate confocal Raman microscopy as a general, nonperturbative tool to measure spatially resolved lithium ion concentrations in liquid electrolytes. By combining this high-spatial-resolution technique with a simple microfluidic device, we are able to measure the diffusion coefficient of lithium ions in dimethyl carbonate in two different concentration regimes. Because lithium ion transport plays a key role in the function of a variety of electrochemical devices, quantifying and visualizing this process is crucial for understanding device performance. This method for detecting lithium ions should be immediately useful in the study of lithium-ion-based devices, ion transport in porous media, and at electrode-electrolyte interfaces, and the analytical framework is useful for any system exhibiting a concentration-dependent Raman spectrum. PMID- 26273888 TI - Enhancing the Performance of Sensitized Solar Cells with PbS/CH3NH3PbI3 Core/Shell Quantum Dots. AB - We report on the fabrication of PbS/CH3NH3PbI3 (=MAP) core/shell quantum dot (QD) sensitized inorganic-organic heterojunction solar cells on top of mesoporous (mp) TiO2 electrodes with hole transporting polymers (P3HT and PEDOT: PSS). The PbS/MAP core/shell QDs were in situ-deposited by a modified successive ionic layer adsorption and reaction (SILAR) process using PbI2 and Na2S solutions with repeated spin-coating and subsequent dipping into CH3NH3I (=MAI) solution in the final stage. The resulting device showed much higher efficiency as compared to PbS QD-sensitized solar cells without a MAP shell layer, reaching an overall efficiency of 3.2% under simulated solar illumination (AM1.5, 100 mW.cm(-2)). From the measurement of the impedance spectroscopy and the time-resolved photoluminescence (PL) decay, the significantly enhanced performance is mainly attributed to both reduced charge recombination and better charge extraction by MAP shell layer. In addition, we demonstrate that the MAP shell effectively prevented the photocorrosion of PbS, resulting in highly improved stability in the cell efficiency with time. Therefore, our approach provides method for developing high performance QD-sensitized solar cells. PMID- 26273889 TI - Thermodynamics versus Kinetics Dichotomy in the Linear Self-Assembly of Mixed Nanoblocks. AB - We report classical and replica exchange molecular dynamics simulations that establish the mechanisms underpinning the growth kinetics of a binary mix of nanorings that form striped nanotubes via self-assembly. A step-growth coalescence model captures the growth process of the nanotubes, which suggests that high aspect ratio nanostructures can grow by obeying the universal laws of self-similar coarsening, contrary to systems that grow through nucleation and elongation. Notably, striped patterns do not depend on specific growth mechanisms, but are governed by tempering conditions that control the likelihood of depropagation and fragmentation. PMID- 26273890 TI - Low Critical Micelle Concentration Discrepancy between Theory and Experiment. AB - Experimental measurements for a variety of surfactants unexpectedly show that the critical micelle concentration (CMC) becomes constant with respect to increasing the size of the hydrophobic tail. This observation disagrees with theoretical models where it is expected to continue to decrease exponentially. Because of the lack of a satisfactory explanation for such a discrepancy from theory, we have studied these systems using a coarse-grained model within the single-chain mean field (SCMF) theory combined with relevant micellar kinetic effects. In particular, a microscopic model for poly(ethylene oxide) alkyl ether was applied to describe a series of nonionic gemini surfactants. When kinetic effects are used to correct the equilibrium CMC values from the SCMF scheme together with the loss of surfactants due to adsorption on the experimental recipient, it is possible to reproduce the correct order of magnitude of the experimental CMC results. Hence it appears that the experimental values disagree with the theoretical predictions because they are not true equilibrium values due to the fact that the time scales for these low CMC values become astronomically large. PMID- 26273891 TI - Electrocatalytic CO2 Reduction with a Homogeneous Catalyst in Ionic Liquid: High Catalytic Activity at Low Overpotential. AB - We describe a new strategy for enhancing the efficiency of electrocatalytic CO2 reduction with a homogeneous catalyst, using a room-temperature ionic liquid as both the solvent and electrolyte. The electrochemical behavior of fac-ReCl(2,2' bipyridine)(CO)3 in neat 1-ethyl-3-methylimidazolium tetracyanoborate ([emim][TCB]) was compared with that in acetonitrile containing 0.1 M [Bu4N][PF6]. Two separate one-electron reductions occur in acetonitrile (-1.74 and -2.11 V vs Fc(+/0)), with a modest catalytic current appearing at the second reduction wave under CO2. However, in [emim][TCB], a two-electron reduction wave appears at -1.66 V, resulting in a ~0.45 V lower overpotential for catalytic reduction of CO2 to CO. Furthermore, the apparent CO2 reduction rate constant, kapp, in [emim][TCB] exceeds that in acetonitrile by over one order of magnitude (kapp = 4000 vs 100 M(-1) s(-1)) at 25 +/- 3 degrees C. Supported by time resolved infrared measurements, a mechanism is proposed in which an interaction between [emim](+) and the two-electron reduced catalyst results in rapid dissociation of chloride and a decrease in the activation energy for CO2 reduction. PMID- 26273892 TI - Including Tunneling in Non-Born-Oppenheimer Simulations. AB - For electronically nonadiabatic processes in all but the simplest systems, the most practical multidimensional simulation method is a semiclassical approximation in which a trajectory or the center of a wave packet follows a classical path governed by an effective potential energy function. Here, we show how such simulations can be made more realistic by including tunneling by the army ants tunneling method. We illustrate the theory by calculations with model potential energy surfaces; one model study is in the adiabatic limit, and the other one has nonadiabatic transitions between two electronic states during the tunneling event. The army ants tunneling algorithm is used to efficiently sample tunneling events in the trajectories in both cases. This work makes it possible to simulate complex nonadiabatic chemical processes by efficiently including the important quantum effect of tunneling. PMID- 26273893 TI - Quantum Localization of Coherent pi-Electron Angular Momentum in (P)-2,2' Biphenol. AB - Controlling pi-electrons with delocalized character is one of the fundamental issues in femtosecond and attosecond chemistry. Localization of pi-electron rotation by using laser pulses is expected to play an essential role in nanoscience. The pi-electron rotation created at a selected aromatic ring of a single molecule induces a local intense electromagnetic field, which is a new type of ultrafast optical control functioning. We propose a quantum localization of coherent pi-electron angular momentum in (P)-2,2'-biphenol, which is a simple, covalently linked chiral aromatic ring chain molecule. The localization considered here consists of sequential two steps: the first step is to localize the pi-electron angular momentum at a selected ring of the two benzene rings, and the other is to maintain the localization. Optimal control theory was used for obtaining the optimized electric fields of linearly polarized laser pulses to realize the localization. The optimal electric fields and the resultant coherent electronic dynamics are analyzed. PMID- 26273894 TI - An Organocatalysis Based Carbocyclic Spiroindoline Synthesis Enables Facile Structure-Activity Relationship (SAR) Study at C2 Position. AB - An asymmetric synthesis of carbocyclic spiroindoline by sequential Michael reaction and [3 + 2]-cycloaddition is described. This protocol demonstrates excellent enantio- and diastereoselectivity with broad functional group tolerance. A diverse range of spiroindolines were prepared by this approach, and the products served as ideal substrates for C2 derivatization. PMID- 26273895 TI - Methylenebisnicotiflorin: a rare methylene-bridged bisflavonoid glycoside from ripe Pu-er tea. AB - A new methylene-bridged dimeric flavonol glycoside, methylenebisnicotiflorin (1), was isolated from ripe Pu-er tea, along with 10 known flavonoids (2-11) and seven known phenolic compounds (12-18). The structure elucidation was based on spectroscopic analysis. Among them, 1,3-dihydroxyphenyl-2-O-sulfate (13), 2,3,4 trihydroxybenzoic acid (16) and 3,3',4,4'-tetrahydroxybiphenyl (18) are reported from tea plants for the first time. PMID- 26273896 TI - Materialistic Values and Goals. AB - Materialism comprises a set of values and goals focused on wealth, possessions, image, and status. These aims are a fundamental aspect of the human value/goal system, standing in relative conflict with aims concerning the well-being of others, as well as one's own personal and spiritual growth. Substantial evidence shows that people who place a relatively high priority on materialistic values/goals consume more products and incur more debt, have lower-quality interpersonal relationships, act in more ecologically destructive ways, have adverse work and educational motivation, and report lower personal and physical well-being. Experimentally activating materialistic aims causes similar outcomes. Given these ills, researchers have investigated means of decreasing people's materialism. Successful interventions encourage intrinsic/self-transcendent values/goals, increase felt personal security, and/or block materialistic messages from the environment. These interventions would likely be more effective if policies were also adopted that diminished contemporary culture's focus on consumption, profit, and economic growth. PMID- 26273897 TI - Scientific Misconduct. AB - Scientific misconduct has been defined as fabrication, falsification, and plagiarism. Scientific misconduct has occurred throughout the history of science. The US government began to take systematic interest in such misconduct in the 1980s. Since then, a number of studies have examined how frequently individual scientists have observed scientific misconduct or were involved in it. Although the studies vary considerably in their methodology and in the nature and size of their samples, in most studies at least 10% of the scientists sampled reported having observed scientific misconduct. In addition to studies of the incidence of scientific misconduct, this review considers the recent increase in paper retractions, the role of social media in scientific ethics, several instructional examples of egregious scientific misconduct, and potential methods to reduce research misconduct. PMID- 26273898 TI - Justice and Negotiation. AB - This review article examines the literature regarding the role played by principles of justice in negotiation. Laboratory experiments and high-stakes negotiations reveal that justice is a complex concept, both in relation to attaining just outcomes and to establishing just processes. We focus on how justice preferences guide the process and outcome of negotiated exchanges. Focusing primarily on the two types of principles that have received the most attention, distributive justice (outcomes of negotiation) and procedural justice (process of negotiation), we introduce the topic by reviewing the most relevant experimental and field or archival research on the roles played by these justice principles in negotiation. A discussion of the methods used in these studies precedes a review organized in terms of a framework that highlights the concept of negotiating stages. We also develop hypotheses based on the existing literature to point the way forward for further research on this topic. PMID- 26273899 TI - The Presence of Sterols Favors Sticholysin I-Membrane Association and Pore Formation Regardless of Their Ability to Form Laterally Segregated Domains. AB - Sticholysin I (St I) is a pore-forming toxin (PFT) produced by the Caribbean Sea anemone Stichodactyla helianthus belonging to the actinoporin protein family, a unique class of eukaryotic PFT. As for actinoporins, it has been proposed that the presence of cholesterol (Chol) and the coexistence of lipid phases increase binding to the target membrane and pore-forming ability. However, little is known about the role of membrane structure and dynamics (phase state, fluidity, and the presence of lipid domains) on the activity of actinoporins or which regions of the membrane are the most favorable for protein insertion, oligomerization, and eventually pore formation. To gain insight into the role of membrane properties on the functional activity of St I, we studied its binding to monolayers and vesicles of phosphatidylcholine (PC), sphingomyelin (SM), and sterols inducing (ergosterol -Erg and cholesterol -Chol) or not (cholestenone - Cln) membrane phase segregation in liquid ordered (Lo) and liquid disordered (Ld) domains. This study revealed that St I binds and permeabilizes with higher efficiency sterol containing membranes independently of their ability to form domains. We discuss the results in terms of the relevance of different membrane properties for the actinoporins mechanism of action, namely, molecular heterogeneity, specially potentiated in membranes with sterols inducers of phase separation (Chol or Erg) or Cln, a sterol noninducer of phase separation but with a high propensity to induce nonlamellar phase. The role of the Ld phase is pointed out as the most suitable platform for pore formation. In this regard, such regions in Chol containing membranes seem to be the most favored due to its increased fluidity; this property promotes toxin insertion, diffusion, and oligomerization leading to pore formation. PMID- 26273901 TI - Oxidation of Actinyl(V) Complexes by the Addition of Nitrogen Dioxide Is Revealed via the Replacement of Acetate by Nitrite. AB - The gas-phase complexes AnO2(CH3CO2)2(-) are actinyl(V) cores, An(V)O2(+) (An = U, Np, Pu), coordinated by two acetate anion ligands. Whereas the addition of O2 to U(V)O2(CH3CO2)2(-) exothermically produces the superoxide complex U(VI)O2(O2)(CH3CO2)2(-), this oxidation does not occur for Np(V)O2(CH3CO2)2(-) or Pu(V)O2(CH3CO2)2(-) because of the higher reduction potentials for Np(V) and Pu(V). It is demonstrated that NO2 is a more effective electron-withdrawing oxidant than O2, with the result that all three An(V)O2(CH3CO2)2(-) exothermically react with NO2 to form nitrite complexes, An(VI)O2(CH3CO2)2(NO2)( ). The assignment of the NO2(-) anion ligand in these complexes, resulting in oxidation from An(V) to An(VI), is substantiated by the replacement of the acetate ligands in AnO2(CH3CO2)2(NO2)(-) and AnO2(CH3CO2)3(-) by nitrites, to produce the tris(nitrite) complexes AnO2(NO2)3(-). The key chemistry of oxidation of An(V) to An(VI) by the addition of neutral NO2 is established by the substitution of acetate by nitrite. The replacement of acetate ligands by NO2(-) is attributed to a metathesis reaction with nitrous acid to produce acetic acid and nitrite. PMID- 26273900 TI - Instant Oatmeal Increases Satiety and Reduces Energy Intake Compared to a Ready to-Eat Oat-Based Breakfast Cereal: A Randomized Crossover Trial. AB - BACKGROUND: Foods that enhance satiety can help consumers to resist environmental cues to eat and help adherence to calorie restriction. The objective of this study was to compare the effect of 2 oat-based breakfast cereals on appetite, satiety, and food intake. METHODS: Forty-eight healthy individuals, 18 years of age or older, were enrolled in a randomized, crossover trial. Subjects consumed isocaloric servings of either oatmeal or an oat-based ready-to-eat breakfast cereal (RTEC) in random order at least a week apart. Visual analogue scales measuring appetite and satiety were completed before breakfast and throughout the morning. Lunch was served 4 hours after breakfast. The physicochemical properties of oat soluble fiber (beta-glucan) were determined. Appetite and satiety responses were analyzed by area under the curve. Food intake and beta-glucan properties were analyzed using t tests. RESULTS: Oatmeal increased fullness (p = 0.001) and reduced hunger (p = 0.005), desire to eat (p = 0.001), and prospective intake (p = 0.006) more than the RTEC. Energy intake at lunch was lower after eating oatmeal compared to the RTEC (p = 0.012). Oatmeal had higher viscosity (p = 0.03), beta-glucan content, molecular weight (p < 0.001), and radius of gyration (p < 0.001) than the RTEC. CONCLUSIONS: Oatmeal suppresses appetite, increases satiety, and reduces energy intake compared to the RTEC. The physicochemical properties of beta-glucan and sufficient hydration of oats are important factors affecting satiety and subsequent energy intake. PMID- 26273902 TI - Isolation of a Cyclic Depsipetide, Aspergillicin F, and Synthesis of Aspergillicins with Innate Immune-Modulating Activity. AB - Innate immunity is the front line of self-defense against microbial infection. After searching for natural compounds that regulate innate immunity using an ex vivo Drosophila culture system, we identified a new cyclic depsipeptide, aspergillicin F, from the fungus Aspergillus sp., as an innate immune suppressor. The total synthesis and biological evaluation of the aspergillicin family, including aspergillicin F, were performed, revealing that slight structural differences in the side chains of amino acid residues alter innate immunity regulating activity. PMID- 26273903 TI - Top-down control and directed attention in self-reference effects: Goal-directed movements and the SAN. AB - We focus on Humphreys and Sui's postulations that self-reference effects are not necessarily pre-attentive, and the self and top-down attention interact in the SAN. If so, top-down factors (goal-relevance, directed attention) should interact with self-reference effects. Our pilot data from unspeeded reach-to-grasp actions show differences in trajectories when reaching toward self- or other-relevant objects. We speculate that goal-directed actions are suited to studying the top down control in self-reference effects. Because goal-directed action paradigms allow broad scope for modulating attention and top-down control, they will be useful for disambiguating the roles of directed attention, inhibition, and (social) context. PMID- 26273904 TI - Apolar Radical Initiated Conjugated Autoxidizable Triene (ApoCAT) Assay: Effects of Oxidant Locations on Antioxidant Capacities and Interactions. AB - Development of an antioxidant assay explaining antioxidant behaviors in complex food systems has been a challenging topic for food scientists. This research aimed to investigate antioxidant capacities and interactions of selected synthetic antioxidants and commercial natural antioxidant extracts using the CAT assay and a newly developed ApoCAT assay, which used water- and lipid-soluble azo radical initiators, respectively. Results suggested that the higher the hydrophobicity of an antioxidant, the higher the antioxidant capacity of an antioxidant observed in the ApoCAT assay. The relationship between the two different assays was explained by the ratio between the ApoCAT and the CAT values. Interestingly, all lipophilic derivatives of the antioxidants exhibited higher ApoCAT/CAT ratios than their hydrophilic derivatives. In the case of the commercial food-grade antioxidants, green tea extract and mixed tocopherols showed a higher antioxidant capacity in the ApoCAT assay than in the CAT assay, while grape seed and rosemary extracts did not show significantly different changes in behaviors in both assays. The study on antioxidant interactions revealed that additive, synergistic, and antagonistic effects between hydrophilic antioxidants and natural extracts, and mixed tocopherols could be observed in both the CAT and the ApoCAT assays, depending on the combined ratios. In most cases, at a particular ratio, the synergistic effect reached the maximum level before suddenly dropping to additive and antagonistic effects in both assays. PMID- 26273905 TI - A new peptide ligand for colon cancer targeted delivery of micelles. AB - Ligands are an imperative part of targeted drug delivery systems, and choosing a ligand with high affinity is a subject of considerable interest. In this study, we first synthesized a 12-residue peptide (TK) that interacts with integrin alpha6beta1 overexpressed on colonic cancer cells. The molecular binding affinity assay indicated that TK had a high binding affinity for integrin alpha6beta1. The results of cellular and tumor spheroid uptake suggested that TK peptide not only increases Caco-2 cells uptake, but also effectively increases penetration of the tumor spheroids. TK-conjugated PEG-PLA was synthesized to prepare a novel PEG-PLA micelles loading DOX or coumarin-6 (TK-MS/DOX or TK-MS/C6). The obtained TK MS/DOX exhibited uniform, spherical shape with a size of 23.80 +/- 0.32 nm and zeta potential of 12.21 +/- 0.31 mV. The release behavior of DOX from micelles were observed no significant changes after TK modification, however, the release profile exhibited pH-sensitive properties. Compared with MS/DOX, TK-MS/DOX exhibited significantly stronger cytotoxicity for Caco-2. Confocal laser microscopy and flow cytometry data further indicated that the targeting micelles not only had higher uptake by Caco-2 cells, but also more effectively penetrated the tumor spheroids. Therefore, TK peptide appears to be suitable as a targeting ligand with potential applications in colonic targeted therapy. PMID- 26273906 TI - Intraocular distribution of topically applied hydrophilic and lipophilic substances in rat eyes. AB - PURPOSE: Topical administration is the preferred route of drug delivery for ophthalmic ailments. However, poor permeation through ocular surface and significant systemic absorption, makes the topical drug delivery challenging. Furthermore, distribution of topically delivered drugs varies with their physicochemical properties and the type of formulation used. Hence, this study was done to understand the pattern of ocular drug distribution of topically applied hydrophilic and lipophilic substances in two different formulations. METHODS: 5-Carboxyfluorescein and 1,1'-dioctadecyl-3,3,3',3' tetramethylindocarbocyanine perchlorate were used as representative candidates for hydrophilic and lipophilic substances, respectively. They were formulated in solution and liposomes. Single drop of either formulation containing hydrophilic or lipophilic substance was instilled topically, unilaterally to rat eyes. Subsequently, rats were sacrificed at 10, 30 and 120 min post-instillation. Eyes were cryosectioned and examined under confocal microscope to determine the fluorescence intensity in ocular tissues. RESULTS: Corneal permeation of hydrophilic and lipophilic substances in both formulations peaked at 30 min post instillation. Liposomal-lipophilic dye and non-liposomal-hydrophilic dye showed better corneal distribution. Fluorescence was absent in contralateral eyes of non liposomal-hydrophilic dye-treated animals but was present in contralateral eyes of liposomal-hydrophilic dye-treated animals. Fluorescence in contralateral eyes of liposomal-lipophilic dye-treated animals was significantly higher compared to non-liposomal-lipophilic dye-treated animals. CONCLUSIONS: Topically applied liposomal formulation of lipophilic substance provides higher corneal concentration of drug with lesser systemic absorption compared to its solution. For hydrophilic substance, topical use of solution provides greater corneal concentration compared to liposomes which is more likely to be absorbed systemically. PMID- 26273907 TI - Ultrasound-responsive nanobubbles contained with peptide-camptothecin conjugates for targeted drug delivery. AB - To improve the targeting delivery efficiency of anticancer drug to tumor sites, a new strategy combining cell-permeable peptide (CPP) and ultrasound was reported in this article. In this study, we devised and tested a strategy for functional payload delivery to cells by loading CPP-camptothecin conjugate (CPP-CPT) into nanobubble (CPP-CPT NB). Here, CPP existing in the conjugation form of CPP and CPT was hidden in nanobubble to cloak the penetration activity of CPP. Meanwhile, local tumor ultrasound was utilized to achieve specific targeting of CPP-CPT to the tumor cells. The mean particle size of the prepared CPP-CPT NB was ~200 nm, and the drug entrapment efficiency was >80%. Stimulated by ultrasound, over 90% of the entrapped CPP-CPTs would release from the nanobubbles. Subsequent research demonstrated that the CPP-CPT NB showed effective cellular uptake and significant cytotoxic activity in HeLa cells in vitro. Additionally, after systemic administration in mice, CPP-CPT NB with ultrasound showed a higher tumor inhibition effect in nude mice xenografted HeLa cells tumors and excellent body safety when compared with normal CPT injection group. In conclusion, the carrier constructed in this study would be a safe and efficiently drug delivery system for specific cancer treatment. PMID- 26273909 TI - Corrigendum. PMID- 26273908 TI - Wouter G van Doorn, December 13, 1951--May 16, 2015. PMID- 26273912 TI - Why an Actigraphy Manual Is Needed. PMID- 26273911 TI - Scientific Discoveries: What Is Required for Lasting Impact. AB - I have been involved in two scientific discoveries of some impact. One is the discovery of long-term potentiation (LTP), the phenomenon that brief, high frequency impulse activity at synapses in the brain can lead to long-lasting increases in their efficiency of transmission. This finding demonstrated that synapses are plastic, a property thought to be necessary for learning and memory. The other discovery is that nerve-evoked muscle impulse activity, rather than putative trophic factors, controls the properties of muscle fibers. Here I describe how these two discoveries were made, the unexpected difficulties of reproducing the first discovery, and the controversies that followed the second discovery. I discuss why the first discovery took many years to become generally recognized, whereas the second caused an immediate sensation and entered textbooks and major reviews but is now largely forgotten. In the long run, discovering a new phenomenon has greater impact than falsifying a popular hypothesis. PMID- 26273913 TI - The SBSM Guide to Actigraphy Monitoring: Clinical and Research Applications. PMID- 26273910 TI - Fail-safe transcription termination: Because one is never enough. AB - Termination of RNA polymerase II (RNAPII) transcription is a fundamental step of gene expression that involves the release of the nascent transcript and dissociation of RNAPII from the DNA template. As transcription termination is intimately linked to RNA 3' end processing, termination pathways have a key decisive influence on the fate of the transcribed RNA. Quite remarkably, when reaching the 3' end of genes, a substantial fraction of RNAPII fail to terminate transcription, requiring the contribution of alternative or "fail-safe" mechanisms of termination to release the polymerase. This point of view covers redundant mechanisms of transcription termination and how they relate to conventional termination models. In particular, we expand on recent findings that propose a reverse torpedo model of termination, in which the 3'5' exonucleolytic activity of the RNA exosome targets transcription events associated with paused and backtracked RNAPII. PMID- 26273916 TI - The complete mitochondrial genome of the Metriaclima zebra. AB - Cichlid fish from East Africa are remarkable for phenotypic and behavioral diversity on a backdrop of genomic similarity. Metriaclima zebra is a member of the Cichlidae family. Here, we reported the complete mitogenome sequence of M. zebra, which was 16 582 bp and contained 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and 1 non-coding control region. A phylogenetic tree was constructed based on complete mitogenomes of M. zebra and 11 closely related Cichlidae species to approve the accuracy. The complete mitochondrial genome of the M. zebra would provide more information for the research of M. zebra and the evolution of Cichlidae family. PMID- 26273920 TI - The complete mitochondrial genome of dwarf danio, Danio nigrofasciatus. AB - In this study, we report the complete mitochondrial genome sequence of dwarf danio, Danio nigrofasciatus, for the first time. The genome is found to be 16 616 bp in length and has a base composition of A (31.97%), G (15.88%), C (23.99%), and T (28.16%), indicating that the percentage of A + T (60.13%) was higher than G + C (39.87%). The mitochondrial genome contains a typically conserved structure including 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNA), 2 ribosomal RNA genes (rRNA), and 1 control region (D-loop). Most of the genes were located on the H-strand except for the ND6 gene and 8 tRNA genes. To obtain a more complete understanding of the evolutionary history between the dwarf danio and other species, 11 mitochondrial genomes were used for phylogenetic analysis. This mitochondrial sequence reported here would be useful to uncover the D. nigrofasciatus evolution and add a new genetic resource for the genus Danio. PMID- 26273922 TI - Complete mitochondrial genome of Sebastes taczanowskii (Scorpaenidae, Scorpaeniformes) from the East Sea, Korea. AB - Sebastes taczanowskii is a subarctic species in the north-western Pacific Ocean. To obtain mitochondrial DNA sequences for phylogeny, the complete mitogenome (16 452 bp in length) of S. taczanowskii was constructed using next-generation sequencing. The circular mitogenome contains 13 protein-coding genes (PCGs), 2 rRNAs, 22 tRNAs and the control region, for which gene structure and positions were similar to those of other Scorpaenidae. The complete mitogenome composed of 27.8% A, 26.5% T, 17.3% G and 28.5% C, with a slight AT bias (54.3%). All PCGs use a typical start codon, ATG, except COX1 (GTG). The terminal codon of PCGs was mainly TAR, with the exceptions of ND4 (AGA) and Cytb (incomplete codon, T). Sebastes taczanowskii was clearly divided from other Scorpaenidae in the phylogenetic tree using 2 rRNA and 13 PCGs. The mitogenome of S. taczanowskii can be useful for constructing the molecular phylogenetic tree within Scorpaenidae. PMID- 26273927 TI - CE: Acute Pain Management for Inpatients with Opioid Use Disorder. AB - OVERVIEW: Like most hospital inpatients, those with opioid use disorder (OUD) often experience acute pain during their hospital stay and may require opioid analgesics. Unfortunately, owing to clinicians' misconceptions about opioids and negative attitudes toward patients with OUD, such patients may be inadequately medicated and thus subjected to unrelieved pain and unnecessary suffering. This article reviews current literature on the topic of acute pain management for inpatients with OUD and dispels common myths about opioids and OUD. PMID- 26273928 TI - CE: Sexually Transmitted Infections in the United States: Overview and Update. AB - OVERVIEW: Sexually transmitted infections (STIs) are the most common infectious diseases in the United States. They have enormous human consequences, including severe reproductive complications, neonatal injury, and death; and because STIs are associated with social stigma, they also have substantial psychological impact. The economic consequences are also enormous: it's estimated that STIs cost the nation about $16 billion in annual health care costs. All communities are affected, although significant racial, ethnic, and other disparities persist. Nurses play a critical role in educating patients on STIs, screening for disease, and providing treatment. Nurses can also help minimize the impact of social stigma by providing informed, confidential, and sensitive care, and by promoting sexual health. This article provides an overview of the symptoms, screening methods, and treatment recommendations for the most common STIs in the United States and describes the most recent relevant findings in order to inform nursing practice. PMID- 26273929 TI - Eleven Basic Procedures/Practices for Dental Patient Safety. AB - OBJECTIVES: This study aimed to help alleviate the shortage of reliable information on clinical care issues; the Spanish Observatory of Dental Patient Safety (OESPO) has resorted to the study of legal claims by patients and searched those which produced clinical problems. METHODS: Based on OESPO data, this article proposes 11 basic procedures/practices for dental patient safety to help mitigate most preventable adverse events. RESULTS: The sample of the OESPO is large (415 adverse events studied), but it has the bias of a judicial source. However, the results provide an interesting approach to clinical safety in dentistry. When studying in detail the causes that led to preventable adverse events, it can be seen that most of these (and most severe) events have been caused by a small number of erroneous behaviors. CONCLUSIONS: Most preventable adverse events during the dental health care are produced by a relatively small number of causes. Therefore, a few basic safety procedures can reduce significantly these preventable adverse events. PMID- 26273930 TI - Frequency and Severity of Adverse Drug Events by Medication Classes: The JADE Study. AB - OBJECTIVE: Adverse drug events (ADEs) are a significant concern in daily practice; however, the profile of high-risk drugs remains unclear. Our objective was to categorize high-risk medication classes according to frequency and severity of ADEs. METHODS: The JADE study is a prospective cohort study of 3459 hospitalized adult patients. We investigated the ADEs and medications prescribed to the patients. The rate of ADEs for each medication class was calculated by dividing the number of ADEs by the number of patients who received each medication class on admission. RESULTS: Overall, 14,435 medications were ordered on admission for patients (median 4; interquartile range, 2-6). Electrolytes and fluids were most frequently prescribed (1876 patients, 54%). Sedatives, antibiotics, peptic ulcer drugs, and analgesics were also commonly prescribed. The frequency was similar in both elderly and younger patients. Among 1010 identified ADEs, antibiotics were most frequently associated with ADEs (31 ADEs per 100 prescribed patients on admission). In patients 65 years and older, corticosteroids, anticonvulsants, laxatives, nonsteroidal anti-inflammatory drugs, and antipsychotics were the 5 most frequent medication classes causing ADEs following antibiotics. In patients younger than 65 years, antibiotics were also the most frequent cause of ADEs, followed by laxatives, lipid-lowering agents, anticonvulsants, and corticosteroids. Among cardiovascular agent associated ADEs, 46% were fatal or life threatening in elderly patients, whereas antihypertensives were most often associated with fatal or life-threatening ADEs (25%) in younger patients. CONCLUSIONS: The medication classes frequently associated with ADEs did not necessarily induce severe ADEs. PMID- 26273931 TI - SEGMENTAL PATTERN OF INFILTRATES OVER RETINAL VESSELS IN FUNGAL ENDOPHTHALMITIS. AB - PURPOSE: To describe the case of a patient with Candida tropicalis endophthalmitis who presented with a pattern of segmentally distributed preretinal infiltrates overlying the retinal blood vessels. METHODS: A retrospective chart review was performed. A 72-year-old East Indian male presented with redness, pain, photosensitivity, and loss of vision in the right eye for 1 month. He had been recently hospitalized for necrotizing pancreatitis and had been receiving intravenous medications as well as parenteral nutrition through a peripherally inserted central catheter. RESULTS: Fundus examination revealed moderate vitreous cells and infiltrates, including a segmental pattern of preretinal bead-like opacities along several blood vessels. The patient underwent emergent vitrectomy with injection of antibiotics and antifungal medications. Vitreous cultures grew C. tropicalis. The patient was treated with oral antifungal medication for 6 weeks. By 7 weeks after surgery, all infiltrates and inflammatory cells had completely resolved. The imaging and intraoperative observations suggest that the opacities behaved like infiltrates and were associated with vitreous rather than vascular inflammation. CONCLUSION: A segmental pattern of preretinal infiltrates over retinal vessels can be a presenting feature in endogenous fungal endophthalmitis. The observations in this case may contribute to understanding the pathophysiology of the findings. PMID- 26273932 TI - Oral Contraceptive Use and Reproductive Characteristics Affect Survival in Patients With Epithelial Ovarian Cancer: A Cohort Study. AB - OBJECTIVES: Prognostic risk factors influencing survival in patients with epithelial ovarian cancer (EOC) include tumor stage, grade, histologic subtype, debulking, and platinum status. Little is known about the impact of hormonal milieu and reproductive factors before cancer diagnosis on clinical outcome. We sought to evaluate whether oral contraceptive (OC) use carries any prognostic significance on overall survival (OS) in patients with EOC. METHODS: Newly diagnosed patients with EOC, fallopian tube, and primary peritoneal cancers between 1982 and 1998 were prospectively evaluated with a comprehensive epidemiologic questionnaire. A retrospective chart review was performed to abstract clinicopathologic data, including OS. A Kaplan-Meier analysis was performed to compare survival across various exposures. A Cox regression model was used to compute adjusted hazards ratios (aHRs) and 95% confidence intervals (CIs). RESULTS: We identified 387 newly diagnosed cancers with evaluable information in this cohort. Decreased risk of death was observed in women who reported prior use of OC (aHR, 0.79; 95% CI, 0.58-1.09), previous pregnancy (aHR, 0.77; 95% CI, 0.57-1.04), or a live birth (aHR, 0.81; 95% CI, 0.60-1.08) after adjusting for age at diagnosis, stage, and histologic subtype. Oral contraceptive use was associated with a crude reduced risk of death (HR, 0.55; 95% CI, 0.42 0.72), with reported median OS of 81 months in OC users versus 46 months in nonusers. Patients who reported a single live birth experienced the largest potential survival advantage (aHR, 0.61; 95% CI, 0.39-0.94). Oral contraceptive use and prior pregnancy were associated with improved survival across all strata. CONCLUSIONS: Oral contraceptive use may have lasting effects on epithelial ovarian tumor characteristics conferring favorable prognosis. Putative mechanisms that affect tumor biology include complex interactions between ovarian cells, host immune cells, and hormonal microenvironment during carcinogenesis. Future efforts should be directed to determine the role of reproductive factors in antitumor immunity. PMID- 26273933 TI - Developing an Anti-Xa-Based Anticoagulation Protocol for Patients with Percutaneous Ventricular Assist Devices. AB - Because of the complexities associated with anticoagulation in temporary percutaneous ventricular assist device (pVAD) recipients, a lack of standardization exists in their management. This retrospective analysis evaluates current anticoagulation practices at a single center with the aim of identifying an optimal anticoagulation strategy and protocol. Patients were divided into two cohorts based on pVAD implanted (CentriMag (Thoratec; Pleasanton, CA) / TandemHeart (CardiacAssist; Pittsburgh, PA) or Impella (Abiomed, Danvers, MA)), with each group individually analyzed for bleeding and thrombotic complications. Patients in the CentriMag/TandemHeart cohort were subdivided based on the anticoagulation monitoring strategy (activated partial thromboplastin time (aPTT) or antifactor Xa unfractionated heparin (anti-Xa) values). In the CentriMag/TandemHeart cohort, there were five patients with anticoagulation titrated based on anti-Xa values; one patient developed a device thrombosis and a major bleed, whereas another patient experienced major bleeding. Eight patients received an Impella pVAD. Seven total major bleeds in three patients and no thrombotic events were detected. Based on distinct differences between the devices, anti-Xa values, and outcomes, two protocols were created to guide anticoagulation adjustments. However, anticoagulation in patients who require pVAD support is complex with constantly evolving anticoagulation goals. The ideal level of anticoagulation should be individually determined using several coagulation laboratory parameters in concert with hemodynamic changes in the patient's clinical status, the device, and the device cannulation. PMID- 26273934 TI - Enhanced Extracorporeal CO2 Removal by Regional Blood Acidification: Effect of Infusion of Three Metabolizable Acids. AB - Acidification of blood entering a membrane lung (ML) with lactic acid enhances CO2 removal (VCO2ML). We compared the effects of infusion of acetic, citric, and lactic acids on VCO2ML. Three sheep were connected to a custom-made circuit, consisting of a Hemolung device (Alung Technologies, Pittsburgh, PA), a hemofilter (NxStage, NxStage Medical, Lawrence, MA), and a peristaltic pump recirculating ultrafiltrate before the ML. Blood flow was set at 250 ml/min, gas flow (GF) at 10 L/min, and recirculating ultrafiltrate flow at 100 ml/min. Acetic (4.4 M), citric (0.4 M), or lactic (4.4 M) acids were infused in the ultrafiltrate at 1.5 mEq/min, for 2 hours each, in randomized fashion. VCO2ML was measured by the Hemolung built-in capnometer. Circuit and arterial blood gas samples were collected at baseline and during acid infusion. Hemodynamics and ventilation were monitored. Acetic, citric, or lactic acids similarly enhanced VCO2ML (+35%), from 37.4 +/- 3.6 to 50.6 +/- 7.4, 49.8 +/- 5.6, and 52.0 +/- 8.2 ml/min, respectively. Acids similarly decreased pH, increased pCO2, and reduced HCO3 of the post-acid extracorporeal blood sample. No significant effects on arterial gas values, ventilation, or hemodynamics were observed. In conclusion, it is possible to increase VCO2ML by more than one-third using any one of the three metabolizable acids. PMID- 26273935 TI - Twelve Hours In Vitro Biocompatibility Testing of Membrane Oxygenators. AB - In vitro test systems for extracorporeal membrane oxygenation (mock loop) represent an interesting alternative to complex and expensive in vivo test systems to analyze the pathomechanisms leading to insufficient biocompatibility. Data on mock loop systems are limited, and operation times are constricted to a maximum duration of 6 hr. This study aims at a 12 hr operation time and frequent monitoring of markers for insufficient biocompatibility in two experimental settings. Porcine blood circulated in a mock loop without any modifications, or the circuit was operated with a CO2-enhanced gas (5% CO2/21% O2/74% N2) in combination with a nutrient solution (phosphate-adenine-glucose-guanosine-saline mannitol). Coagulation parameters changed over time without differences between the two groups. In the unmodified test setting, a pH increase was detected after 1 hr, followed by significantly increased levels of free hemoglobin as a marker for hemolysis and elevated numbers of activated platelets, which correlate with detected von Willebrand factor, microparticles, and interleukin-beta. Proinflammatory cytokine levels were significantly increased after 12 hr. In contrast, these parameters remained constant in the modified test setting providing proof of a stable operating in vitro mock loop system with an extended/prolonged operation time. PMID- 26273936 TI - Maternal and Fetal Recovery After Severe Respiratory Failure: A Case Report of Air Transportation of a Pregnant Woman on ECMO Using the CentriMag Transporter System. AB - Use of extracorporeal membrane oxygenation (ECMO) for severe cardiopulmonary failure has increased because of improved outcomes. A specially designed ECMO transport system allows for safe transport of patients over long distances. We report a 28-year-old pregnant woman (26 weeks gestation) with acute respiratory distress syndrome in whom ECMO support was necessary for survival, and she was transported to another facility 1,155 km away with the aid of the portable ECMO system. Transport was uneventful, and the patient's condition remained stable. Acute respiratory distress syndrome improved gradually until the patient was discharged from the hospital with excellent maternal and fetal outcome. PMID- 26273937 TI - Interactions Between Modality of Working Memory Load and Perceptual Load in Distractor Processing. AB - The present study investigated interactions between working memory load and perceptual load. The load theory (Lavie, Hirst, de Fockert, & Viding, 2004 ) claims that perceptual load decreases distractor interference, whereas working memory load increases interference. However, recent studies showed that effects of working memory might depend on the relationship between modalities of working memory and task stimuli. Here, we examined whether the relationship between working memory load and perceptual load would remain the same across modalities. The results of Experiment 1 showed that verbal working memory load did not affect a compatibility effect for low perceptual load, whereas it increased the compatibility effect for high perceptual load. In Experiment 2, the compatibility effect remained the same regardless of visual working memory load. These results suggest that the effects of working memory load and perceptual load depend on the relationship between the modalities of working memory and stimuli. PMID- 26273938 TI - The Impact of Multifaceted Questions on Eyewitness Accuracy Following Forced Fabrication Interviews. AB - Lawyers will frequently use complex-question forms, such as multifaceted questions (single questions that contain both a true and a false proposition), when cross-examining witnesses, and prior research has shown that use of such questions reduces testimonial accuracy. The present study extends this research by using a forced fabrication paradigm (Chrobak & Zaragoza, 2008) to assess how multifaceted questions might affect eyewitness suggestibility after exposure to misleading post-event information. Consistent with prior studies, the use of multifaceted questions led to lower accuracy than simple questions. The novel finding was that multifaceted questions caused larger impairments in performance among fabrication participants (who had earlier been suggestively interviewed), than in control participants (who had not). We also provide preliminary evidence that the impairment caused by multifaceted questions is due to both (a) having to consider two propositions simultaneously, and (b) the shift in question focus from the fabricated event to a true event. PMID- 26273939 TI - Simulating Personal Wealth in the Laboratory. AB - During laboratory gambling tasks participants are not typically allowed to wager their personal wealth. Instead, wealth is simulated by telling participants they have been endowed with game tokens that will be later exchanged for money. Past research indicates that participants undervalue game tokens following this procedure, which leads to elevated risk taking compared to procedures that add saliency or realism to the monetary payoff. A between-subjects experiment tested whether showing a picture of money during the endowment instructions and repeating token-money exchange information during the session influenced participants' preference for risky and riskless options. The results showed no effect of the money picture. However, repeated token-money exchange information significantly decreased risk taking. Together with past studies, this finding suggests that endowment procedures might establish greater value in game tokens, and therefore better simulate personal wealth, when the eventual exchange between game tokens and money is made more salient to participants. PMID- 26273940 TI - The Name-Pronunciation Effect: Further Evidence from Chinese. AB - This study examined the Chinese name-pronunciation effect. The easy-to-pronounce and difficult-to-pronounce Chinese names were created using the same characters in order to control for visual perceptual and conceptual fluency. In Experiment 1, participants rated each name in terms of liking, electability as a state leader, income level, and baby name preference. An additional rating of prevalence was used to estimate familiarity. In Experiment 2, participants did not read the name aloud before rating and performed intentional recall and recognition tests. In both experiments, the easy-to-pronounce names were rated higher than difficult-to-pronounce names on liking. This effect generalized to judgments of electability and baby name preference but not to prevalence and income level. There were no differences in memory performances between the two types of names. Results are discussed in terms of the boundary condition of the name-pronunciation effect and the advantage of using Chinese names to study this effect. PMID- 26273941 TI - A Call for Considering Color Vision Deficiency When Creating Graphics for Psychology Reports. AB - Although color vision deficiency (CVD) is fairly common, it is often not adequately considered when data is presented in color graphics. This study found that CVD tends to be mentioned neither in the author guidelines of psychology journals nor in the standard publication manuals of the field (e.g., the publication manuals of the American Psychological Association and the American Medical Association). To illustrate the relevance of this problem, a panel of scholars with CVD was used to evaluate the color figures in three respected psychological science journals. Results suggested that a substantial proportion of those figures were needlessly confusing for viewers with CVD and could have been easily improved through simple adjustments. Based on prior literature and on feedback from the panelists, recommendations are made for improving the accessibility of graphics in psychology reports. PMID- 26273942 TI - [New oral anticoagulants in antiphospholipid syndrome]. PMID- 26273943 TI - [Clinical usefulness of Beta2microglobulin in patients with Primary Sjogren Syndrome]. AB - The extraglandular manifestations and lymphoproliferative disorders are complications in pSS. There are few serological markers that they are useful in these conditions. OBJETIVES: to evaluate the usefulness of the beta2microglobulin level in patients with pSS and its relation to extra glands manifestations , lymphoproliferative disorders and the presence of Rheumatoid factor (RF), serum immunoglobulins (Igs), and C3 and C4 levels. MATERIAL AND METHODS: we retrospectively studied patients with pSS , OAD and healthy controls . Ig G, Ig A and Ig M levels, serum complement C3 and C4 and RF were performed by immunoturbidimetry, and beta2microglobulin protein by the ELISA technique in all patients. RESULTS: 19 patients with pSS (Group SSp), 28 patients with other autoimme diseases diferent from pSS (Group PAD) and 24 healthy controls (Group C).There was an signifcant increase of beta2m values in Groups SS and OAD vs Group C (6.19 mg/dl vs. 2.53 mg/dl p<0.001) and (4.38 mg/dl vs. 2.53 mg/dl p<0.01). On the other hand, mean beta2m levels in Group SS were higher than in Group OAD (6.19 vs. 4.38 mg/dl p<0.01).There was not a relationship between beta2m level and Ig G, A , M ,complement levels and the presence of RF. CONCLUSION: beta2m can discriminate patients with pSS from those with other autoimmune diseases and healthy subjects. Increased beta2m level in pattients with pSS could reflect hyperactivation of B cells and it could be a potential marker associated with extraglandular manifestations and cell lymphoproliferative disorders. PMID- 26273944 TI - [Characteristics of diabetes mellitus patients under a chronic disease program]. AB - Diabetes Mellitus (DM) is a chronic noncommunicable disease with a prevalence of 9.8% in Argentina. A Chronic Disease Program was developed for monitoring of patients with DM at the Ambulatory Center of DASPU, in National University of Cordoba Argentina. OBJECTIVE: To describe clinical characteristics of DM patients under a chronic disease program and to identify metabolic control variables associated with the presence of complications. MATERIAL AND METHODS: Observational, cross-sectional, descriptive study of DM Patients who attended at ambulatory center of DASPU since 2010. Categorical variables were described as proportions and number as mean +/- SD. The comparison of means was performed using student test. RESULTS: 1017 patients were analyzed with mean age of 61 +/- 14 years, with 54.6% of male, 8.5% had type 1 DM, and 90.9% had DM type 2: O.7% had gestational DM. Cardiovascular risk factor were: hypertension in 78%, dyslipidemia in 35. 25.5% of patients had micro vascular complications and 18.6% had macro vascular complications. Coronary heart disease was the most frequent complication in 14.5% of the patients. . 69% had values of glycated hemoglobin (HbA1C) <= 7, 4%; the average total cholesterol was 185 mg / dl and LDL cholesterol 111 mg / dl. The average HbA1C was higher in patients with micro vascular complications, HbA1c 7.47% vs. 7.18% (p = 0.009). In patients with macrovascular complications there was no significant inverse trend, HbA1c 7.21% vs 7.26% with and without complications (p = 0.65). The average total cholesterol was lower in the group with macro vascular complications 173 mg / dl and 189 mg / dl (p = 0.001). Similar result was observed in LDL-C: 101 vs 113 mg / dl (p = 0.001) in patients with and without complications, respectively. CONCLUSION: Clinical characteristics of the patients under the program were similar to other studies reported in the literature, but the values of HbA1c and total cholesterol have better results, achieving optimal values in a large percentage of the population, with lower levels in patients with macrovascular complications. PMID- 26273945 TI - [Resident of emergency attitude towards patients-physician relationship at the Hospital de Clinicas- Asuncion, Paraguay]. AB - INTRODUCTION: The doctor-patient relationship is reaching great importance in recent times, is highlighted their importance in areas as varied as satisfaction, compliance, perception of professional competence, the frequency of legal issues relating to malpractice and even the prognosis of the disease or the general health of the patient. OBJECTIVE: To evaluate the doctor-patient relationship from the point of view of residents of emergency unit. METHODS: An observational, descriptive study. The sample consisted of 36 doctors from different areas of the Emergency Rooms of the Hospital de Clinicas- Asuncion, Paraguay. The patient physician relationship was evaluated using an instrument developed by RA Chavarria-Islas et al. with four indicators: Respect, Information, Consent and Dedication. RESULTS: 69.4% of residents have a regular patient-physician relationship; despite the 2.78% has a good relationship, 25% bad relationship and 2.78% a very bad relationship. CONCLUSION: Gaps in doctor-patient relationship were found in this study.. It is interesting to invest greater efforts to enhance the doctor-patient relationship as one of the edges to improve health care, which is vital in emergency care. PMID- 26273946 TI - [Pituitary tumors: 10 years of experience]. AB - INTRODUCTION: Pituitary tumors comprise a quarter of the intracranial neoplasms and the adenomas represent the highest percentage of them. They are benign, but they can be invasive and they have an impact in morbidity and mortality. OBJECTIVE: To analyze the clinical features of pituitary adenomas tumors, and create a computerized registry to improve strategies for diagnosis and monitoring of these patients. METHODS: A retrospective, descriptive analysis of 102 medical records of a total of 191 patients who attended the endocrinology service from 2003 to 2014 .The variables were analyzed by the corresponding descriptive statistics. The SPSS 11.5 was used. RESULTS: 63% were women, and (74.4%) had age from 25-60 years. 54% were nonfunctioning adenomas, 28% to prolactinomas, 11.8% and 6.2% somatotropinomas corticotropinomas. In all types the female group was predominant, except nonfunctioning. Of the nonfunctioning adenomas 79% were macroadenomas, prolactinomas 52% were microadenomas and surgery was performed in 37% of them. The somatotropinomas, 80% were macroadenomas, 80% of patients and 40% radiotherapy was operated. In corticotropinomas, both micro and macroadenomas were submitted by the same percentage (50%) and all of them underwent surgery. CONCLUSION: The findings are consistent with the literature in terms of frequency and age of onset of adenomas. We suggest the development of a registry to optimize the monitoring and treatment of patients, research and scientific publication. PMID- 26273947 TI - [Statins and osteoporosis]. PMID- 26273948 TI - [Asomatognosia as a manifestation of migraine with aura. case report and review]. AB - INTRODUCTION: For years the study of migraine with aura was surprised by the versatility of its presentation. Auras are manifested with the gradual development of neurological symptoms ranging from visual impairment to perception disorders. The latter are rare forms of presentation being the reason for this article. CASE REPORT: the case of a female patient of 53 years diagnosed with migraine with aura which makes an autobiographical account of their crises, with special emphasis on a variant of asomatognosia as manifestation is presented. It then discusses the asomatognosia as a phenomenon belonging to the altered body image and the different concepts related to these clinical forms and a brief overview of the possible anatomical locations of these conditions do. CONCLUSION: Migraine with aura may manifest with varied previous symptoms before the pain. The asomatognosia is an uncommon presentation. A field of interests for research also include an effort to define the specificity and location of the lesion as a method for better understanding of how injuries to very specific areas of the brain affect perception and memory. PMID- 26273951 TI - Generation of long, fully modified, and serum-resistant oligonucleotides by rolling circle amplification. AB - Rolling Circle Amplification (RCA) is an isothermal enzymatic method generating single-stranded DNA products consisting of concatemers containing multiple copies of the reverse complement of the circular template precursor. Little is known on the compatibility of modified nucleoside triphosphates (dN*TPs) with RCA, which would enable the synthesis of long, fully modified ssDNA sequences. Here, dNTPs modified at any position of the scaffold were shown to be compatible with rolling circle amplification, yielding long (>1 kb), and fully modified single-stranded DNA products. This methodology was applied for the generation of long, cytosine rich synthetic mimics of telomeric DNA. The resulting modified oligonucleotides displayed an improved resistance to fetal bovine serum. PMID- 26273950 TI - Engaging Patients With Advance Directives Using an Information Visualization Approach. AB - Despite the benefits of advance directives (AD) to patients and care providers, they are often not completed due to lack of patient awareness. The purpose of the current article is to advocate for creation and use of an innovative information visualization (infovisual) as a health communication tool aimed at improving AD dissemination and engagement. The infovisual would promote AD awareness by encouraging patients to learn about their options and inspire contemplation and conversation regarding their end-of-life (EOL) journey. An infovisual may be able to communicate insights that are often communicated in words, but are much more powerfully communicated by example. Furthermore, an infovisual could facilitate vivid understanding of options and inspire the beginning of often difficult conversations among care providers, patients, and loved ones. It may also save clinicians time, as care providers may be able to spend less time explaining details of EOL care options. Use of an infovisual could assist in ensuring a well planned EOL journey. PMID- 26273949 TI - Characterization of Distinct Macrophage Subpopulations during Nitrogen Mustard Induced Lung Injury and Fibrosis. AB - Nitrogen mustard (NM) is an alkylating agent known to cause extensive pulmonary injury progressing to fibrosis. This is accompanied by a persistent macrophage inflammatory response. In these studies, we characterized the phenotype of macrophages accumulating in the lung over time following NM exposure. Treatment of rats with NM (0.125 mg/kg, intratracheally) resulted in an increase in CD11b(+) macrophages in histologic sections. These cells consisted of inducible nitric oxide synthase(+) (iNOS) proinflammatory M1 macrophages, and CD68(+), CD163(+), CD206(+), YM-1(+), and arginase-II(+)antiinflammatory M2 macrophages. Although M1 macrophages were prominent 1-3 days after NM, M2 macrophages were most notable at 28 days. At this time, they were enlarged and vacuolated, consistent with a profibrotic phenotype. Flow cytometric analysis of isolated lung macrophages identified three phenotypically distinct subpopulations: mature CD11b(-), CD43(-), and CD68(+) resident macrophages, which decreased in numbers after NM; and two infiltrating (CD11b(+)) macrophage subsets: immature CD43(+) M1 macrophages and mature CD43(-) M2 macrophages, which increased sequentially. Time related increases in M1 (iNOS, IL-12alpha, COX-2, TNF-alpha, matrix metalloproteinase-9, matrix metalloproteinase-10) and M2 (IL-10, pentraxin-2, connective tissue growth factor, ApoE) genes, as well as chemokines/chemokine receptors associated with trafficking of M1 (CCR2, CCR5, CCL2, CCL5) and M2 (CX3CR1, fractalkine) macrophages to sites of injury, were also noted in macrophages isolated from the lung after NM. The appearance of M1 and M2 macrophages in the lung correlated with NM-induced acute injury and the development of fibrosis, suggesting a potential role of these macrophage subpopulations in the pathogenic response to NM. PMID- 26273952 TI - Reconstructing and analysing cellular states, space and time from gene expression profiles of many cells and single cells. AB - Genome-wide gene expression profiling is a fast, cheap and standardised analysis that provides a high dimensional measurement of the state of a biological sample. In this review we describe computational methods that can be applied to identify and interpret sources of variance in gene expression in whole organisms, organs, tissues or single cells. This allows the identification of constituent cell types and states in complex mixtures, the reconstruction of temporal trajectories of development, differentiation and progression, and the reconstruction of spatial patterning. When applied to genetically variable samples, these methods allow the efficient investigation of how genetic variation influences gene expression and biological processes in space and time. PMID- 26273953 TI - Controlled growth of large area multilayer graphene on copper by chemical vapour deposition. AB - The growth of nearly full coverage of multilayer graphene on the surface of a 99.8% purity copper foil has been experimentally studied. It has been shown that the film thickness can be controlled by a single parameter, the growth time, and growth can be extended until nearly full coverage of more than one layer graphene over the copper surface. The results are supported by scanning electron microscopy and Raman analysis together with optical transmittance and sheet resistance measurements. It has been verified that silicon oxide impurity particles within the copper act as catalysts and the seeds of multilayer graphene islands. The linear increase of the average thickness of graphene to the growth time has been attributed to the interplay between the mean distance between the impurities on the surface and the molecular mean free path in the process gas. A qualitative model is proposed to explain the microscopic mechanism of the multilayer growth on copper. These results contribute to the understanding of the chemical vapour deposition growth kinetics towards the objective of large area high quality graphene production with tuneable layer thickness. PMID- 26273954 TI - Surgical Injury to the Mouse Pancreas through Ligation of the Pancreatic Duct as a Model for Endocrine and Exocrine Reprogramming and Proliferation. AB - Expansion of pancreatic beta cells in vivo or ex vivo, or generation of beta cells by differentiation from an embryonic or adult stem cell, can provide new expandable sources of beta cells to alleviate the donor scarcity in human islet transplantation as therapy for diabetes. Although recent advances have been made towards this aim, mechanisms that regulate beta cell expansion and differentiation from a stem/progenitor cell remain to be characterized. Here, we describe a protocol for an injury model in the adult mouse pancreas that can function as a tool to study mechanisms of tissue remodeling and beta cell proliferation and differentiation. Partial duct ligation (PDL) is an experimentally induced injury of the rodent pancreas involving surgical ligation of the main pancreatic duct resulting in an obstruction of drainage of exocrine products out of the tail region of the pancreas. The inflicted damage induces acinar atrophy, immune cell infiltration and severe tissue remodeling. We have previously reported the activation of Neurogenin (Ngn) 3 expressing endogenous progenitor-like cells and an increase in beta cell proliferation after PDL. Therefore, PDL provides a basis to study signals involved in beta cell dynamics and the properties of an endocrine progenitor in adult pancreas. Since, it still remains largely unclear, which factors and pathways contribute to beta cell neogenesis and proliferation in PDL, a standardized protocol for PDL will allow for comparison across laboratories. PMID- 26273956 TI - Continuous, High-Speed, and Efficient Oil/Water Separation using Meshes with Antagonistic Wetting Properties. AB - We report a novel oil/water separation device, allowing continuous, high-speed, and highly efficient purification of large volumes of oily water. This device uses a pair of hydrophilic/hydrophobic polymer-brush-functionalized stainless steel meshes, which have antagonistic wetting properties, i.e., superoleophobic and superhydrophobic properties, when submerged in the opposite liquid phase. This device can purify large volumes of n-hexadecane/water mixture (~1000 L) in a continuous process rather than in batches, to high purities (~99.9% mol/mol) at high flow rates (~5 mL s(-1) cm(-2)), unlike the oil/water separation meshes reported so far. PMID- 26273955 TI - Enrichment of Extracellular Matrix Proteins from Tissues and Digestion into Peptides for Mass Spectrometry Analysis. AB - The extracellular matrix (ECM) is a complex meshwork of cross-linked proteins that provides biophysical and biochemical cues that are major regulators of cell proliferation, survival, migration, etc. The ECM plays important roles in development and in diverse pathologies including cardio-vascular and musculo skeletal diseases, fibrosis, and cancer. Thus, characterizing the composition of ECMs of normal and diseased tissues could lead to the identification of novel prognostic and diagnostic biomarkers and potential novel therapeutic targets. However, the very nature of ECM proteins (large in size, cross-linked and covalently bound, heavily glycosylated) has rendered biochemical analyses of ECMs challenging. To overcome this challenge, we developed a method to enrich ECMs from fresh or frozen tissues and tumors that takes advantage of the insolubility of ECM proteins. We describe here in detail the decellularization procedure that consists of sequential incubations in buffers of different pH and salt and detergent concentrations and that results in 1) the extraction of intracellular (cytosolic, nuclear, membrane and cytoskeletal) proteins and 2) the enrichment of ECM proteins. We then describe how to deglycosylate and digest ECM-enriched protein preparations into peptides for subsequent analysis by mass spectrometry. PMID- 26273957 TI - 3D musculoskeletal finite element analysis of the foot kinematics under muscle activation with and without ankle arthrodesis. PMID- 26273958 TI - Atomic Force Microscopy Imaging and Force Spectroscopy of Supported Lipid Bilayers. AB - Atomic force microscopy (AFM) is a versatile, high-resolution imaging technique that allows visualization of biological membranes. It has sufficient magnification to examine membrane substructures and even individual molecules. AFM can act as a force probe to measure interactions and mechanical properties of membranes. Supported lipid bilayers are conventionally used as membrane models in AFM studies. In this protocol, we demonstrate how to prepare supported bilayers and characterize their structure and mechanical properties using AFM. These include bilayer thickness and breakthrough force. The information provided by AFM imaging and force spectroscopy help define mechanical and chemical properties of membranes. These properties play an important role in cellular processes such as maintaining cell hemostasis from environmental stress, bringing membrane proteins together, and stabilizing protein complexes. PMID- 26273959 TI - Intravital Microscopy Imaging of the Liver following Leishmania Infection: An Assessment of Hepatic Hemodynamics. AB - Intravital microscopy (IVM) is a powerful optical imaging technique that has made possible the visualization, monitoring and quantification of various biological events in real time and in live animals. This technology has greatly advanced our understanding of physiological processes and pathogen-mediated phenomena in specific organs. In this study, IVM is applied to the mouse liver and protocols are designed to image in vivo the circulatory system of the liver and measure red blood cell (RBC) velocity in individual hepatic vessels. To visualize the different vessel subtypes that characterize the hepatic organ and perform blood flow speed measurements, C57Bl/6 mice are intravenously injected with a fluorescent plasma reagent that labels the liver-associated vasculature. IVM enables in vivo, real time, measurement of RBC velocity in a specific vessel of interest. Establishing this methodology will make it possible to investigate liver hemodynamics under physiological and pathological conditions. Ultimately, this imaging-based methodology will be important for studying the influence of L. donovani infection on hepatic hemodynamics. This method can be applied to other infectious models and mouse organs and might be further extended to pre-clinical testing of a drug's effect on inflammation by quantifying its effect on blood flow. PMID- 26273960 TI - A New Type of ECT Stimuli: Burst Stimulus ECT. AB - OBJECTIVES: Pulse width in electroconvulsive therapy has significant influence on effectiveness and side effects. While shorter pulses are beneficial for cognitive performance, there is still a debate about a negative impact on ECT efficacy at least for ultra-brief pulse durations. METHODS: We report a first patient treated with burst stimulus ECT, i. e., with 4 consecutive 250-us pulses, separated by another 250 us. Within the same patient we compared 6 classical vs. 6 burst stimulus ECT sessions. RESULTS: In all cases a typical tonic-clonic seizure was observed. Seizure parameters like concordance, coherence and mid-ictal amplitude increased numerically, but not significantly with burst ECT. The time needed to show a reorientation was significantly shortened with burst stimuli (30 min vs. 14 min, p=0.007). CONCLUSIONS: In conclusion we present the first case of ECT in a single patient comparing "classical" single stimulus pulses vs. burst stimulus ECT. The new burst stimulus was better tolerated regarding reorientation time after the treatment, while parameters of seizure quality remained basically unchanged. Whether burst stimulus ECT has the potential to improve ECT quality by reducing side effects without losing efficacy has to be investigated in clinical trials. PMID- 26273961 TI - Fabrication of Gate-tunable Graphene Devices for Scanning Tunneling Microscopy Studies with Coulomb Impurities. AB - Owing to its relativistic low-energy charge carriers, the interaction between graphene and various impurities leads to a wealth of new physics and degrees of freedom to control electronic devices. In particular, the behavior of graphene's charge carriers in response to potentials from charged Coulomb impurities is predicted to differ significantly from that of most materials. Scanning tunneling microscopy (STM) and scanning tunneling spectroscopy (STS) can provide detailed information on both the spatial and energy dependence of graphene's electronic structure in the presence of a charged impurity. The design of a hybrid impurity graphene device, fabricated using controlled deposition of impurities onto a back gated graphene surface, has enabled several novel methods for controllably tuning graphene's electronic properties. Electrostatic gating enables control of the charge carrier density in graphene and the ability to reversibly tune the charge and/or molecular states of an impurity. This paper outlines the process of fabricating a gate-tunable graphene device decorated with individual Coulomb impurities for combined STM/STS studies. These studies provide valuable insights into the underlying physics, as well as signposts for designing hybrid graphene devices. PMID- 26273962 TI - Rumination and self-defining memories in the context of health concerns. AB - Individuals with health anxiety report experiencing a strong sense of vulnerability to illness. Such beliefs may be driven by the biased recollection of past illness-related events. However, little research has explored the role of memory in health anxiety. In other disorders, rumination has also been identified as a process that leads individuals to recall memories dominated by the content of their concerns. This study examined the proposition that rumination might impact the content of "self-defining" autobiographical memories among 60 college students with varying health anxiety (35% with clinical-level health anxiety). Participants were randomised to experiential/ruminative self-focus conditions, and then they completed the Self-Defining Memory Task. Responses were coded for valence and illness-relatedness. Results indicated that rumination led participants to retrieve more illness-related self-defining memories, while higher health anxiety scores were associated with more negative, but not more illness-focused memories. Ruminative thinking appears to activate health concerns, and may play a role in maintaining ongoing health anxiety. PMID- 26273964 TI - Proton-Coupled Electron Transfer in the Reduction of Arenes by SmI2-Water Complexes. AB - The presence of water has a significant impact on the reduction of substrates by SmI2. The reactivity of the Sm(II)-water reducing system and the relationship between sequential or concerted electron-transfer, proton-transfer is not well understood. In this work, we demonstrate that the reduction of an arene by SmI2 water proceeds through an initial proton-coupled electron transfer. The use of thermochemical data available in the literature shows that upon coordination of water to Sm(II) in THF, significant weakening of the O-H bond occurs. The derived value of nearly 73 kcal/mol for the decrease in the bond dissociation energy of the O-H bond in the Sm(II)-water complex is the largest reported to date for low valent reductants containing bound water. PMID- 26273963 TI - Visual Evoked Potential Recording in a Rat Model of Experimental Optic Nerve Demyelination. AB - The visual evoked potential (VEP) recording is widely used in clinical practice to assess the severity of optic neuritis in its acute phase, and to monitor the disease course in the follow-up period. Changes in the VEP parameters closely correlate with pathological damage in the optic nerve. This protocol provides a detailed description about the rodent model of optic nerve microinjection, in which a partial demyelination lesion is produced in the optic nerve. VEP recording techniques are also discussed. Using skull implanted electrodes, we are able to acquire reproducible intra-session and between-session VEP traces. VEPs can be recorded on individual animals over a period of time to assess the functional changes in the optic nerve longitudinally. The optic nerve demyelination model, in conjunction with the VEP recording protocol, provides a tool to investigate the disease processes associated with demyelination and remyelination, and can potentially be employed to evaluate the effects of new remyelinating drugs or neuroprotective therapies. PMID- 26273965 TI - Completeness of HIV reporting on death certificates for Floridians reported with HIV infection, 2000-2011. AB - Human immunodeficiency virus (HIV) mortality is used as a key measure to monitor the impact of HIV throughout the world. It is important that HIV be correctly recorded on death certificates so that the burden of HIV mortality can be tracked accurately. The objective of this study was to determine the extent of failure to correctly report HIV on death certificates and examine patterns of incompleteness by demographic factors. Causes of death on death certificates of people infected with HIV reported to the Florida HIV surveillance system 2000-2011 were analyzed to determine the proportion without mention of HIV who had an underlying cause of death suggestive of HIV based on World Health Organization recommendations. Of the 11,989 deaths, 8089 (67.5%) had an HIV code (B20-B24, R75) as any of the causes of death, 3091 (25.8%) had no mention of HIV and the underlying cause was not suggestive of HIV, and 809 (6.7%) had no mention of HIV but the underlying cause was suggestive of HIV. Therefore, 9.1% (809/8898) of probable HIV-related deaths had no mention of HIV on the death certificate. Dying within 1 month of HIV diagnosis was the factor most strongly associated with no mention of HIV when the underlying cause was suggestive of HIV on the death certificate. The results suggest that HIV mortality using only vital records may underestimate actual HIV mortality by approximately 9%. Efforts to reduce incompleteness of reporting of HIV on death certificates could improve HIV-related mortality estimates. PMID- 26273966 TI - Photochemical Reduction of CO2 Using 1,3-Dimethylimidazolylidene. AB - Product analysis along with fluorescence quenching and laser flash photolysis experiments demonstrate that it is possible to effect a net photochemical reduction of CO2 through photolysis of an excited state donor in the presence of 1,3-dimethylimidazolium-2-carboxylate. PMID- 26273967 TI - Unveiling the Interplay Between Diffusing CO2 and Ethanol Molecules in Champagne Wines by Classical Molecular Dynamics and (13)C NMR Spectroscopy. AB - The diffusion coefficients of carbon dioxide (CO2) and ethanol (EtOH) in carbonated hydroalcoholic solutions and Champagne wines are evaluated as a function of temperature by classical molecular dynamics (MD) simulations and (13)C NMR spectroscopy measurements. The excellent agreement between theoretical and experimental diffusion coefficients suggest that ethanol is the main molecule, apart from water, responsible for the value of the CO2 diffusion coefficients in typical Champagne wines, a result that could likely be extended to most sparkling wines with alike ethanol concentrations. CO2 and EtOH hydrodynamical radii deduced from viscometry measurements by applying the Stokes Einstein relationship are found to be mostly constant and in close agreement with MD predictions. The reliability of our approach should be of interest to physical chemists aiming to model transport phenomena in supersaturated aqueous solutions or water/alcohol mixtures. PMID- 26273968 TI - Ab Initio Thermodynamics of Oxygen Vacancies and Zinc Interstitials in ZnO. AB - ZnO is an important wide band gap semiconductor with potential application in various optoelectronic devices. In the current contribution, we explore the thermodynamics of oxygen vacancies and zinc interstitials in ZnO from first principles phonon calculations. Formation enthalpies are evaluated using hybrid DFT calculations, and phonons are addressed using the PBE and the PBE+U functionals. The phonon contribution to the entropy is most dominant for oxygen vacancies, and their Gibbs formation energy increases when including phonons. Finally, inclusion of phonons decreases the Gibbs formation energy difference of the two defects and is therefore important when predicting their equilibrium concentrations and the electrical activity of ZnO at finite temperatures. PMID- 26273969 TI - Interferometric Plasmonic Lensing with Nanohole Arrays. AB - Nonlinear photoemission electron microscopy (PEEM) of nanohole arrays in gold films is used to map propagating surface plasmons (PSPs) launched from lithographically patterned structures. Strong near-field photoemission patterns are observed in the PEEM images, recorded following low angle of incidence irradiation of nanohole arrays with sub-15 fs laser pulses centered at 780 nm. The recorded photoemission patterns are attributed to constructive and destructive interference between PSPs launched from the individual nanoholes which comprise the array. By exploiting the wave nature of PSPs, we demonstrate how varying the array geometry (hole diameter, pitch, and number of rows/columns) ultimately yields intense localized photoemission. Through a combination of PEEM experiments and finite-difference time-domain simulations, we identify the optimal array geometry for efficient light coupling and interferometric plasmonic lensing. We show a preliminary application of inteferometric plasmonic lensing by enhancing the photoemission from the vertex of a gold triangle using a nanohole array. PMID- 26273970 TI - Accurate and Efficient Model Energies for Exploring Intermolecular Interactions in Molecular Crystals. AB - The energy of interaction between molecules is commonly expressed in terms of four key components: electrostatic, polarization, dispersion, and exchange repulsion. Using monomer wave functions to obtain accurate estimates of electrostatic, polarization, and repulsion energies along with Grimme's dispersion corrections, a series of energy models are derived by fitting to dispersion-corrected DFT energies for a large number of molecular pairs extracted from organic and inorganic molecular crystals. The best performing model reproduces B3LYP-D2/6-31G(d,p) counterpoise-corrected energies with a mean absolute deviation (MAD) of just over 1 kJ mol(-1) but in considerably less computation time. It also performs surprisingly well against benchmark CCSD(T)/CBS energies, with a MAD of 2.5 kJ mol(-1) for a combined data set including Hobza's X40, S22, A24, and S66 dimers. Two of these energy models, the most accurate and the fastest, are expected to find widespread application in investigations of molecular crystals. PMID- 26273971 TI - (19)F-Labeling of Peptides Revealing Long-Range NMR Distances in Fluid Membranes. AB - NMR distance measurements lie at the heart of structural biology. However, long range distances could not yet be detected in liquid-crystalline biomembranes, because dipolar couplings are partially averaged by the intrinsic molecular mobility. Using conformationally constrained (19)F-labeled amino acids as reporter groups, we could more than double the accessible interatomic distance range by combining a highly sensitive solid-state multipulse (19)F-NMR scheme with a favorable sample geometry. Two rigid 4F-phenylglycine labels were placed into the helical antimicrobial peptide PGLa embedded in fluid oriented membrane samples. A modified Carr-Purcell-Meiboom-Gill sequence yielded an intramolecular distance of 6.6 A for the labels spanning one helix turn, and 11.0 A was obtained when the labels spanned two turns. This approach should now also allow the characterization of conformational changes in membrane-active peptides and of oligomeric assemblies in a biologically relevant lipid environment. PMID- 26273972 TI - Phase Behavior and Percolation Properties of the Patchy Colloidal Fluids in the Random Porous Media. AB - The lack of a simple analytical description of the hard-sphere fluid in a matrix with hard-core obstacles is limiting progress in the development of thermodynamic perturbation theories for the fluid in random porous media. We propose a simple and highly accurate analytical scheme, which allows us to calculate thermodynamic and percolation properties of a network-forming fluid confined in the random porous media, represented by the hard-sphere fluid and overlapping hard-sphere matrices, respectively. Our scheme is based on the combination of scaled-particle theory, Wertheim's thermodynamic perturbation theory for associating fluids and extension of the Flory-Stockmayer theory for percolation. The liquid-gas phase diagram and percolation threshold line for several versions of the patchy colloidal fluid model confined in a random porous media are calculated and discussed. The method presented enables calculation of the thermodynamic and percolation properties of a large variety of polymerizing and network-forming fluids confined in random porous media. PMID- 26273973 TI - Diffusion Rates for Hydrogen on Pd(111) from Molecular Quantum Dynamics Calculations. AB - The van Hove formula for the dynamical structure factor (DSF) related to particle scattering at mobile adsorbates is extended to include the relaxation of the adsorbates' vibrational states. The total rate obtained from the DSF is assumed to be the sum of a diffusion and a relaxation rate. A simple kinetic model to support this assumption is presented. To illustrate its potential applicability, the formula is evaluated using wave functions, energies, and lifetimes of vibrational states obtained for H/Pd(111) from first-principle calculations. Results show that quantum effects can be expected to be important even at room temperature. PMID- 26273974 TI - Low-Cost Quantum Chemical Methods for Noncovalent Interactions. AB - The efficient and reasonably accurate description of noncovalent interactions is important for various areas of chemistry, ranging from supramolecular host-guest complexes and biomolecular applications to the challenging task of crystal structure prediction. While London dispersion inclusive density functional theory (DFT-D) can be applied, faster "low-cost" methods are required for large-scale applications. In this Perspective, we present the state-of-the-art of minimal basis set, semiempirical molecular-orbital-based methods. Various levels of approximations are discussed based either on canonical Hartree-Fock or on semilocal density functionals. The performance for intermolecular interactions is examined on various small to large molecular complexes and organic solids covering many different chemical groups and interaction types. We put the accuracy of low-cost methods into perspective by comparing with first-principle density functional theory results. The mean unsigned deviations of binding energies from reference data are typically 10-30%, which is only two times larger than those of DFT-D. In particular, for neutral or moderately polar systems, many of the tested methods perform very well, while at the same time, computational savings of up to 2 orders of magnitude can be achieved. PMID- 26273975 TI - Rapid Dye Regeneration Mechanism of Dye-Sensitized Solar Cells. AB - During the light-harvesting process of dye-sensitized solar cells (DSSCs), the hole localized on the dye after the charge separation yields an oxidized dye, D(+). The fast regeneration of D(+) using the redox pair (typically the I(-)/I3( ) couple) is critical for the efficient DSSCs. However, the kinetic processes of dye regeneration remain uncertain, still promoting vigorous debates. Here, we use molecular dynamics simulations to determine that the inner-sphere electron transfer pathway provides a rapid dye regeneration route of ~4 ps, where penetration of I(-) next to D(+) enables an immediate electron transfer, forming a kinetic barrier. This explains the recently reported ultrafast dye regeneration rate of a few picoseconds determined experimentally. We expect that our MD based comprehensive understanding of the dye regeneration mechanism will provide a helpful guideline in designing TiO2-dye-electrolyte interfacial systems for better performing DSSCs. PMID- 26273976 TI - Low Exciton-Phonon Coupling, High Charge Carrier Mobilities, and Multiexciton Properties in Two-Dimensional Lead, Silver, Cadmium, and Copper Chalcogenide Nanostructures. AB - The development of two-dimensional (2D) nanomaterials has revealed novel physical properties, like high carrier mobilities and the tunable coupling of charge carriers with phonons, which can enable wide-ranging applications in optoelectronic and thermoelectric devices. While mechanical exfoliation of graphene and some transition metal dichalcogenides (e.g., MoS2, WSe2) has enabled their fabrication as 2D semiconductors and integration into devices, lack of similar syntheses for other 2D semiconductor materials has hindered further progress. Here, we report measurements of fundamental charge carrier interactions and optoelectronic properties of 2D nanomaterials made from two-monolayers-thick PbX, CdX, Cu2X, and Ag2X (X = S, Se) using colloidal syntheses. Extremely low coupling of charge carriers with phonons (2-6-fold lower than bulk and other low dimensional semiconductors), high carrier mobilities (0.2-1.2 cm(2) V(-1) s(-1), without dielectric screening), observation of infrared surface plasmons in ultrathin 2D semiconductor nanostructures, strong quantum-confinement, and other multiexcitonic properties (different phonon coupling and photon-to-charge collection efficiencies for band-edge and higher-energy excitons) can pave the way for efficient solution-processed devices made from these 2D nanostructured semiconductors. PMID- 26273977 TI - Cubic In2O3 Microparticles for Efficient Photoelectrochemical Oxygen Evolution. AB - Cubic In2O3 microparticles with exposed {001} facets as well as single morphology and size are produced on a large scale on silicon with a high yield. The morphological evolution during chemical vapor deposition is investigated and the new knowledge enables precise facet cutting. The synthesized Cubic In2O3 microparticles possess superior photoelectrocatalytic activity and excellent chemical and structural stability in oxygen evolution reaction on account of the unique surface structure and electronic band structure of the {001} facets. Our results reveal that it is feasible to promote the photolectrochemical water splitting efficiency of photoanode materials by controlling the growth on specific crystal facets. The technique and concept can be extended to other facet specific materials in applications such as sensors, solar cells, and lithium batteries. PMID- 26273978 TI - Strong Field Adiabatic Ionization Prepares a Launch State for Coherent Control. AB - We demonstrate that excitation of acetophenone with a strong field, near-infrared femtosecond pulse (1150-1500 nm) results in adiabatic ionization, producing acetophenone radical cation in the ground electronic state. The time-resolved transients of the parent and fragment ions probed with a weak 790 nm pulse reveal an order of magnitude enhancement of the peak-to-peak amplitude oscillations, ~ 100 fs longer coherence time, and an order of magnitude increase in the ratio of parent to fragment ions in comparison with nonadiabatic ionization with a strong field 790 nm pulse. Equation of motion coupled cluster and classical wavepacket trajectory calculations support the mechanism wherein the probe pulse excites a wavepacket on the ground surface D0 to the excited D2 surface at a delay of 325 fs, resulting in dissociation to the benzoyl ion. Direct population transfer to the D2 state within the duration of a 1370 nm pump pulse eliminates wavepacket oscillation on the D0 state. PMID- 26273979 TI - Hole Surface Trapping Dynamics Directly Monitored by Electron Spin Manipulation in CdS Nanocrystals. AB - A new detection technique, pump-spin orientation-probe ultrafast spectroscopy, is developed to study the hole trapping dynamics in colloidal CdS nanocrystals. The hole surface trapping process spatially separates the electron-hole pairs excited by the pump pulse, leaves the core negatively charged, and thus enhances the electron spin signal generated by the orientation pulse. The spin enhancement transients as a function of the pump-orientation delay reveal a fast and a slow hole trapping process with respective time constants of sub-10 ps and sub-100 ps, orders of magnitude faster than that of carrier recombination. The power dependence of hole trapping dynamics elucidates the saturation process and relative number of traps, and suggests that there are three subpopulations of nanoparticles related to hole surface trapping, one with the fast trapping pathway only, another with the slow trapping pathway only, and the third with both pathways together. PMID- 26273980 TI - Accurate and Efficient Quantum Chemistry by Locality of Chemical Interactions. PMID- 26273981 TI - Magnetic Properties of Polycrystalline Bismuth Ferrite Thin Films Grown by Atomic Layer Deposition. AB - The atomic layer deposition (ALD) method was applied to grow thin polycrystalline BiFeO3 (BFO) films on Pt/SiO2/Si substrates. The 50 nm thick films were found to exhibit high resistivity, good morphological integrity, and homogeneity achieved by the applied ALD technique. Magnetic characterization revealed saturated magnetization of 25 emu/cm(3) with temperature-dependent coercivity varying from 5 to 530 Oe within the temperature range from 300 to 2 K. Magnetism observed in the films was found to change gradually from ferromagnetic spin ordering to pinned magnetic domain interactions mixed with weak spin-glass-like behavior of magnetically frustrated antiferromagnetic/ferromagnetic (AFM-FM) spin ordering depending on the temperature and magnitude of the applied magnetic field. Antiferromagnetic order of spin cycloids was broken in polycrystalline films by crystal sizes smaller than the cycloid length (~60 nm). Uncompensated spincycloids and magnetic domain walls were found to be the cause of the high magnetization of the BFO films. PMID- 26273982 TI - Self-Assembled, Redox-Active Graphene Electrodes for High-Performance Energy Storage Devices. AB - Graphene-based materials have been utilized as a promising approach in designing high-performance electrodes for energy storage devices. In line with this approach, functionalized graphene electrodes have been self-assembled from the dispersion of graphene oxide (GO) in water at a low temperature of 80 degrees C using tetrahydroxyl-1,4-benzoquinone (THQ) as both the reducing and redox-active functionalization agent. We correlated the electrochemical performance of the electrode with surface oxygen chemistry, confirming the role of THQ for the reduction and redox-active functionalization process. The assembled graphene electrodes have a 3D hierarchical porous structure, which can facilitate electronic and ionic transport to support fast charge storage reactions. Utilizing the surface redox reactions introduced by THQ, the functionalized graphene electrodes exhibit high gravimetric capacities of ~165 mA h/g in Li cells and ~120 mA h/g in Na cells with high redox potentials over ~3 V versus Li or Na, proposing promising positive electrodes for both Li and Na ion batteries. PMID- 26273983 TI - Spectroelectrochemistry of Silver Deposition on Single Gold Nanocrystals. AB - We report the electrodeposition of metallic silver onto gold nanostars adsorbed to ITO electrodes. The electrochemical process was studied at the single particle level by correlated in situ dark field spectroscopy and scanning electron microscopy (SEM). Underpotential deposition avoids bulk silver formation on the ITO substrates. SEM proves that deposition occurs on all surfaces of the gold nanostars when polyvinylpyrrolidone (PVP) is stabilizing the nanostars or preferentially at the nanostar tips when the ligand is removed. The surface plasmon resonance blue-shifts by more than 100 nm following the formation of a 5 nm Ag film on PVP stabilized gold nanostars, moving the scattered color from the near-infrared to red or orange. The spectral shifts can be accurately modeled using finite element simulations. These results demonstrate that the morphology and composition of individual bimetallic nanocrystals can be engineered electrochemically. PMID- 26273984 TI - Xenon Suboxides Stable under Pressure. AB - We present results from first-principles calculations on solid xenon-oxygen compounds under pressure. We find that the xenon suboxide Xe3O2 is the first compound to become more stable than the elements, at around P = 75 GPa. Other, even more xenon-rich compounds follow at higher pressures, while no region of enthalpic stability is found for the monoxide XeO. We establish the spectroscopic fingerprints of a variety of structural candidates for a recently synthesized xenon-oxygen compound at atmospheric pressure and, on the basis of the proposed stoichiometry XeO2, suggest an orthorhombic structure that comprises extended sheets of square-planar-coordinated xenon atoms connected through bent Xe-O-Xe linkages. PMID- 26273985 TI - Mosaic of Water Orientation Structures at a Neutral Zwitterionic Lipid/Water Interface Revealed by Molecular Dynamics Simulations. AB - Ordering of water structures near the surface of biological membranes has been recently extensively studied using interface-selective techniques like vibrational sum frequency generation (VSFG) spectroscopy. The detailed structures of interface water have emerged for charged lipids, but those for neutral zwitterionic lipids remain obscure. We analyze an all-atom molecular dynamics (MD) trajectory of a hydrated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayer to characterize the orientation of interface waters in different chemical environments. The structure and dynamics of interfacial waters strongly depend on both their vertical position along the bilayer normal as well as vicinal lipid charged groups. Water orientation in the vicinity of phosphate groups is opposite to that around choline groups. The results are consistent with observed VSFG spectra and demonstrate that a mosaic of water orientation structures exists on the surface of a neutral zwitterionic phospholipid bilayer, reflecting rapid water exchange and the influence of local chemical environments. PMID- 26273986 TI - Conformer- and Mode-Specific Excited State Lifetimes of Cold Protonated Tyrosine Ions. AB - The excited state lifetimes of conformer- and mode-selected cold protonated tyrosine have been measured for the first time through a picosecond pump-probe photodissociation scheme. Whereas the photofragmentation mechanism of protonated tyrosine ions strongly depends upon the interaction of the carboxylic acid group with the phenol ring, their excited state lifetimes are quite similar and decrease as the excess energy increases from 1.5 ns at the band origin to 900 ps and less than 500 ps for the 10(1) and 10(2) bands, respectively. Surprisingly, the excited state lifetime of the conformer with the anti orientation of the hydroxyl oxygen lone pair with respect to the ammonium group dramatically increases as compared to the others conformers up to 10 ns at the band origin and by more than a factor of 2 for the 10(1) band. The present experimental results clearly emphasize the subtle effect of the structural conformation on the excited state properties of molecular ions. PMID- 26273987 TI - Chromophores in Molecular Nanorings: When Is a Ring a Ring? AB - The topology of a conjugated molecule plays a significant role in controlling both the electronic properties and the conformational manifold that the molecule may explore. Fully pi-conjugated molecular nanorings are of particular interest, as their lowest electronic transition may be strongly suppressed as a result of symmetry constraints. In contrast, the simple Kasha model predicts an enhancement in the radiative rate for corresponding linear oligomers. Here we investigate such effects in linear and cyclic conjugated molecules containing between 6 and 42 butadiyne-linked porphyrin units (corresponding to 600 C-C bonds) as pure monodisperse oligomers. We demonstrate that as the diameter of the nanorings increases beyond ~10 nm, its electronic properties tend toward those of a similarly sized linear molecule as a result of excitation localization on a subsegment of the ring. However, significant differences persist in the nature of the emitting dipole polarization even beyond this limit, arising from variations in molecular curvature and conformation. PMID- 26273988 TI - Electroosmosis through alpha-Hemolysin That Depends on Alkali Cation Type. AB - We demonstrate experimentally the existence of an electroosmotic flow (EOF) through the wild-type nanopore of alpha-hemolysin in a large range of applied voltages and salt concentrations for two different salts, LiCl and KCl. EOF controls the entry frequency and residence time of small neutral molecules (beta cyclodextrins, betaCD) in the nanopore. The strength of EOF depends on the applied voltage, on the salt concentration, and, interestingly, on the nature of the cations in solution. In particular, EOF is stronger in the presence of LiCl than KCl. We interpret our results with a simple theoretical model that takes into account the pore selectivity and the solvation of ions. A stronger EOF in the presence of LiCl is found to originate essentially in a stronger anionic selectivity of the pore. Our work provides a new and easy way to control EOF in protein nanopores, without resorting to chemical modifications of the pore. PMID- 26273989 TI - Exploiting Locality in Quantum Computation for Quantum Chemistry. AB - Accurate prediction of chemical and material properties from first-principles quantum chemistry is a challenging task on traditional computers. Recent developments in quantum computation offer a route toward highly accurate solutions with polynomial cost; however, this solution still carries a large overhead. In this Perspective, we aim to bring together known results about the locality of physical interactions from quantum chemistry with ideas from quantum computation. We show that the utilization of spatial locality combined with the Bravyi-Kitaev transformation offers an improvement in the scaling of known quantum algorithms for quantum chemistry and provides numerical examples to help illustrate this point. We combine these developments to improve the outlook for the future of quantum chemistry on quantum computers. PMID- 26273990 TI - Insights on the structural perturbations in human MTHFR Ala222Val mutant by protein modeling and molecular dynamics. AB - Methylenetetrahydrofolate reductase (MTHFR) protein catalyzes the only biochemical reaction which produces methyltetrahydrofolate, the active form of folic acid essential for several molecular functions. The Ala222Val polymorphism of human MTHFR encodes a thermolabile protein associated with increased risk of neural tube defects and cardiovascular disease. Experimental studies have shown that the mutation does not affect the kinetic properties of MTHFR, but inactivates the protein by increasing flavin adenine dinucleotide (FAD) loss. The lack of completely solved crystal structure of MTHFR is an impediment in understanding the structural perturbations caused by the Ala222Val mutation; computational modeling provides a suitable alternative. The three-dimensional structure of human MTHFR protein was obtained through homology modeling, by taking the MTHFR structures from Escherichia coli and Thermus thermophilus as templates. Subsequently, the modeled structure was docked with FAD using Glide, which revealed a very good binding affinity, authenticated by a Glide XP score of -10.3983 (kcal mol(-1)). The MTHFR was mutated by changing Alanine 222 to Valine. The wild-type MTHFR-FAD complex and the Ala222Val mutant MTHFR-FAD complex were subjected to molecular dynamics simulation over 50 ns period. The average difference in backbone root mean square deviation (RMSD) between wild and mutant variant was found to be ~.11 A. The greater degree of fluctuations in the mutant protein translates to increased conformational stability as a result of mutation. The FAD-binding ability of the mutant MTHFR was also found to be significantly lowered as a result of decreased protein grip caused by increased conformational flexibility. The study provides insights into the Ala222Val mutation of human MTHFR that induces major conformational changes in the tertiary structure, causing a significant reduction in the FAD-binding affinity. PMID- 26273991 TI - Novel regulation of aflatoxin B1 biosynthesis in Aspergillus flavus by piperonal. AB - The present study investigated its inhibitory role in aflatoxin (AF) biosynthesis. Treating only AFB1- and B2-producing Aspergillus flavus with piperonal completely inhibited AFB1 production with high sclerotial formation, resulting in 20-fold higher AFG2 production. On the other hand, benzodioxole and eugenol suppressed AFB1 production without AFG formation, while methyleugenol showed potent inhibition of AFB1 production with slight production of AFG1. These results indicate that natural products may change aflatoxin biosynthesis, and highlight a novel regulation of AFG2 production by piperonal. It is the first report for chemical regulation on AFG2 production in non-AFG producing aspergilli. PMID- 26273992 TI - Oriented Immobilization of Fab Fragments by Site-Specific Biotinylation at the Conserved Nucleotide Binding Site for Enhanced Antigen Detection. AB - Oriented immobilization of antibodies and antibody fragments has become increasingly important as a result of the efforts to reduce the size of diagnostic and sensor devices to miniaturized dimensions for improved accessibility to the end-user. Reduced dimensions of sensor devices necessitate the immobilized antibodies to conserve their antigen binding activity for proper operation. Fab fragments are becoming more commonly used in small-scaled diagnostic devices due to their small size and ease of manufacture. In this study, we used the previously described UV-NBS(Biotin) method to functionalize Fab fragments with IBA-EG11-Biotin linker utilizing UV energy to initiate a photo cross-linking reaction between the nucleotide binding site (NBS) on the Fab fragment and IBA-Biotin molecule. Our results demonstrate that immobilization of biotinylated Fab fragments via UV-NBS(Biotin) method generated the highest level of immobilized Fab on surfaces when compared to other typical immobilization methods while preserving antigen binding activity. UV-NBS(Biotin) method provided 432-fold, 114-fold, and 29-fold improved antigen detection sensitivity than physical adsorption, NHS-Biotin, and epsilon-NH3(+), methods, respectively. Additionally, the limit of detection (LOD) for PSA utilizing Fab fragments immobilized via UV-NBS(Biotin) method was significantly lower than that of the other immobilization methods, with an LOD of 0.4 pM PSA. In summary, site specific biotinylation of Fab fragments without structural damage or loss in antigen binding activity provides a wide range of application potential for UV NBS immobilization technique across numerous diagnostic devices and nanotechnologies. PMID- 26273995 TI - Source attribution and quantification of benzene event emissions in a Houston ship channel community based on real-time mobile monitoring of ambient air. AB - A mobile laboratory equipped with a proton transfer reaction mass spectrometer (PTR-MS) operated in Galena Park, Texas, near the Houston Ship Channel during the Benzene and other Toxics Exposure Study (BEE-TEX). The mobile laboratory measured transient peaks of benzene of up to 37 ppbv in the afternoon and evening of February 19, 2015. Plume reconstruction and source attribution were performed using the four-dimensional (4D) variational data assimilation technique and a three-dimensional (3D) micro-scale forward and adjoint air quality model based on mobile PTR-MS data and nearby stationary wind measurements at the Galena Park Continuous Air Monitoring Station (CAMS). The results of inverse modeling indicate that significant pipeline emissions of benzene may at least partly explain the ambient concentration peaks observed in Galena Park during BEE-TEX. Total pipeline emissions of benzene inferred within the 16-km(2) model domain exceeded point source emissions by roughly a factor of 2 during the observational episode. Besides pipeline leaks, the model also inferred significant benzene emissions from marine, railcar, and tank truck loading/unloading facilities, consistent with the presence of a tanker and barges in the Kinder Morgan port terminal during the afternoon and evening of February 19. Total domain emissions of benzene exceeded corresponding 2011 National Emissions Inventory (NEI) estimates by a factor of 2-6. IMPLICATIONS: Port operations involving petrochemicals may significantly increase emissions of air toxics from the transfer and storage of materials. Pipeline leaks, in particular, can lead to sporadic emissions greater than in emission inventories, resulting in higher ambient concentrations than are sampled by the existing monitoring network. The use of updated methods for ambient monitoring and source attribution in real time should be encouraged as an alternative to expanding the conventional monitoring network. PMID- 26273993 TI - Application of 3D NMR for Structure Determination of Peptide Natural Products. AB - Despite the advances in NMR, structure determination is often slow and constitutes a bottleneck in natural products discovery. Removal of this bottleneck would greatly improve the throughput for antibiotic discovery as well as other therapeutic areas. Overall, faster structure methods for structure determination will serve the natural products community in a broad manner. This report describes the first application of 3D NMR for elucidation of two microbially produced peptide natural products with novel structures. The methods are cost-effective and greatly improve the confidence in a proposed structure. PMID- 26273994 TI - Role of US Contrast Agents in the Assessment of Indeterminate Solid and Cystic Lesions in Native and Transplant Kidneys. AB - Ultrasonography (US) is often the initial imaging modality employed in the evaluation of renal diseases. Despite improvements in B-mode and Doppler imaging, US still faces limitations in the assessment of focal renal masses and complex cysts as well as the microcirculation. The applications of contrast-enhanced US (CEUS) in the kidneys have dramatically increased to overcome these shortcomings with guidelines underlining their importance. This article describes microbubble contrast agents and their role in renal imaging. Microbubble contrast agents consist of a low solubility complex gas surrounded by a phospholipid shell. Microbubbles are extremely safe and well-tolerated pure intravascular agents that can be used in renal failure and obstruction, where computed tomographic (CT) and magnetic resonance (MR) imaging contrast agents may have deleterious effects. Their intravascular distribution allows for quantitative perfusion analysis of the microcirculation, diagnosis of vascular problems, and qualitative assessment of tumor vascularity and enhancement patterns. Low acoustic power real-time prolonged imaging can be performed without exposure to ionizing radiation and at lower cost than CT or MR imaging. CEUS can accurately distinguish pseudotumors from true tumors. CEUS has been shown to be more accurate than unenhanced US and rivals contrast material-enhanced CT in the diagnosis of malignancy in complex cystic renal lesions and can upstage the Bosniak category. CEUS can demonstrate specific enhancement patterns allowing the differentiation of benign and malignant solid tumors as well as focal inflammatory lesions. In conclusion, CEUS is useful in the characterization of indeterminate renal masses and cysts. PMID- 26273996 TI - Linear and T-Shaped Iron(I) Complexes Supported by N-Heterocyclic Carbene Ligands: Synthesis and Structure Characterization. AB - The use of the N-heterocyclic carbene (NHC) ligands 1,3-bis(2',6'-diethylphenyl) 4,5-(CH2)4-imidazol-2-ylidene (cyIDep), 1,3-bis(2',6'-diethylphenyl)-imidazolin-2 ylidene (sIDep), and its N-mesityl analogue sIMes enables the preparation of the two-coordinate homoleptic iron(I)-NHC complexes [(cyIDep)2Fe][BAr(F)4] (3, Ar(F) denoted for 3,5-di(trifluoromethyl)phenyl) and [(sIDep)2Fe][BAr(F)4] (4) and the T-shaped iron(I)-NHC complex [(sIMes)2Fe(THF)][BPh4] (5, THF = tetrahydrofuran). Complexes 3-5 were prepared via the sequential protocol of control reduction of iron(II) dihalides by KC8 in the presence of the corresponding NHC ligands followed by halide-abstraction with NaBAr4. Spectroscopic characterization, including single-crystal X-ray diffraction studies and (57)Fe Mossbauer spectroscopy, in combination with density functional theory calculations, suggest their high-spin nature. Solution property study (absorption spectroscopy and cyclic voltammetry) indicates that 3 and 5 keep their corresponding two- and three-coordinate nature in THF solution, and 4 might reversibly coordinate a THF molecule to form, presumably, the T-shaped species [(sIDep)2Fe(THF)][BAr(F)4]. The isolation of 3 and 4 demonstrates the accessibility of homoleptic two coordinate iron(I)-NHC complexes. PMID- 26273997 TI - Connectivity between ventromedial prefrontal cortex and posterior superior temporal sulcus. AB - The well-articulated Self Attention Network (SAN) framework accounts for a great portion of the available evidence on neurocognitive interactions between self bias phenomena and attention. I argue that more work is necessary to refine our understanding about the effective and functional connectivity of the different nodes of the proposed network. In particular, the nature of the control of ventro medial prefrontal cortex over posterior superior temporal sulcus has to be worked out further. Simple excitatory connections between these two nodes, as proposed by the SAN model, do not satisfactorily account for existing neuropsychological dissociations and are not fully warranted by neuroimaging evidence. PMID- 26273999 TI - REFLECTIONS ON STRATEGIC-SYSTEMIC THERAPY. PMID- 26273998 TI - TWISTS AND TURNS IN STRATEGIC THERAPY: AN INTRODUCTION. PMID- 26274000 TI - IN MEMORIAM: HAROLD A. GOOLISHIAN 1924-1991. PMID- 26274001 TI - STRATEGY AND INTERVENTION VERSUS NONINTERVENTION: A MATTER OF THEORY? AB - The question of whether or not intervention and strategy are necessary components of competent therapy is described and related to the metaphorical assumptions of underlying theory. Passive listening and expert interpretations are consequences of psychodynamic theory. Active manipulation of social structure and strategic intervention into feedback are described as consequences of the mechanical assumptions of structural and cybernetic theory. Conversational participation and non intervention are described as necessary consequences of hermeneutic and linguistic approaches to therapy. It is concluded that different theoretical assumptions yield different conclusions regarding the nature of therapy and human problems. From this perspective the question of Intervention Versus Non Intervention is more a matter of the theory held than a question to be answered in terms of the "right" or "adequate" thing to do or not do. PMID- 26274002 TI - STRATEGIC THERAPY, ECLECTICISM, AND THE THERAPEUTIC RELATIONSHIP. AB - Although profoundly influencing the family field by highlighting the deficiencies of pathology-based views, strategic therapy has come under fire in two general areas: (a) adherence to a "black box" philosophy that discounts the value of intrapersonal phenomena; and (b) interventions that appear exceedingly instrumental, manipulative, and based on a position of therapist power. This article will examine these criticisms in light of the rise of eclecticism and the resurgence of the primacy of the therapeutic relationship. It will be argued that if strategic therapy is to remain viable, it must evolve to include the contributions of other models and consider the relationship context from which intervention arises. PMID- 26274003 TI - THE PROBLEM OF STRATEGY WITHIN THE SYSTEMIC THERAPIES. AB - Strategic principles, because they imply therapist power and influence, have become an object of debate within the systemic therapy movement. This article examines a variety of positions taken in that debate, focusing particularly on those expressed by the other members of the 1990 AAMFT panel "Twists and Turns in Strategic Therapy," namely, Harold Goolishian, Insoo Berg, and Barry Duncan. By considering strategic therapy in terms of the distinction between therapeutic process and content and the distinction between realist and antirealist epistemologies, it is argued that there is more convergence among the proponents of those positions than their writings might have us believe. PMID- 26274004 TI - SOME AFTERTHOUGHTS ON READING DUNCAN AND HELD. PMID- 26274005 TI - STRATEGY AND REALITY: A COMMENT ON GOOLISHIAN, ANDERSON, AND HELD. PMID- 26274006 TI - THE MYTH OF THE UNFEELING STRATEGIC THERAPIST. AB - This paper explores what the authors consider to be a widespread myth: that strategic therapists ignore, avoid, or neglect client feelings in treatment. This myth is promulgated by trainers' admonitions and strategic theorists' injunctions against dealing with client affect. It is also cultivated by omission of this topic in the strategic literature. The myth is destructive in that it misrepresents what strategic practitioners actually do in a therapy session. Seven elements of the myth are delineated and the corresponding fallacies are illustrated. PMID- 26274007 TI - ETHICS AND STRATEGIC THERAPY: A PROPOSED ETHICAL DIRECTION. AB - Although ethical criticisms have been leveled against strategic therapy for some time, the current intensification of such criticisms indicates the need for continued dialogue about ethical strategic practice. This article presents ethical directions in two broad areas often seen as inherent in the strategic approach: (a) conscious deception and (b) intervention outside client awareness. Emerging from a discussion of the clinical implications of a constructivist view and a meaning system vocabulary of client change, five ethical presuppositions are exemplified. The ethical concerns of manipulation, power, and control are also discussed. PMID- 26274008 TI - NONCONFRONTIVE USE OF VIDEO PLAYBACK TO PROMOTE CHANGE IN BRIEF FAMILY THERAPY. AB - This paper describes a nonconfrontive use of video playback in brief family therapy. Replaying critical transactions from previous sessions, while maintaining a neutral and nonconfrontive therapeutic stance, encourages an atmosphere which is conducive to change. The technique allows family members to reexperience their own interactional patterns in a nonthreatening manner, enabling them to consider the meanings they attach to their family experience in different and productive ways. PMID- 26274009 TI - DOING THERAPY: A POST-STRUCTURAL RE-VISION. AB - The purpose of this essay is to develop a way to look at doing therapy based on (a) Wittgenstein's concept of "language game"; (b) the relationship between Wittgenstein's "private language" argument, language games, and constructivism; and (c) post-structural thinking about language, how therapy works within language, and how language works within therapy. Case material is used to illustrate the usefulness of this approach. PMID- 26274010 TI - LETTERS TO THE EDITOR. PMID- 26274012 TI - EDITOR'S REPORT. PMID- 26274013 TI - Circadian rhythmicity of synapses in mouse somatosensory cortex. AB - The circadian rhythmicity displayed by motor behavior of mice: activity at night and rest during the day; and the associated changes in the sensory input are reflected by cyclic synaptic plasticity in the whisker representations located in the somatosensory (barrel) cortex. It was not clear whether diurnal rhythmic changes in synapse density previously observed in the barrel cortex resulted from changes in the activity of the animals, from daily light/dark (LD) rhythm or are driven by an endogenous clock. These changes were investigated in the barrel cortex of C57BL/6 mouse strain kept under LD 12 : 12 h conditions and in constant darkness (DD). Stereological analysis of serial electron microscopic sections was used to assess numerical density of synapses. In mice kept under LD conditions, the total density of synapses and the density of excitatory synapses located on dendritic spines was higher during the light period (rest phase). In contrast, the density of inhibitory synapses located on dendritic spines increased during the dark period (activity phase). Under DD conditions, the upregulation of the inhibitory synapses during the activity phase was retained, but the cyclic changes in the density of excitatory synapses were not observed. The results show that the circadian plasticity concerns only synapses located on spines (and not those on dendritic shafts), and that excitatory and inhibitory synapses are differently regulated during the 24 h cycle: the excitatory synapses are influenced by light, whilst the inhibitory synapses are driven by the endogenous circadian clock. PMID- 26274014 TI - Ligand Control over the Electronic Properties within the Metallic Core of Gold Nanoparticles. AB - The behavior of electrons within the metallic core of gold nanoparticles (AuNPs) can be controlled by the nature of the surface chemistry of the AuNPs. Specifically, the conduction electron spin resonance (CESR) spectra of AuNPs of diameter 1.8-1.9 nm are sensitive to ligand exchange of hexanethiol for 4 bromothiophenol on the surface of the nanoparticle. Chemisorption of the aromatic ligand leads to a shift in the metallic electron's g-factor toward the value expected for pure gold systems, suggesting an increase in metallic character for the electrons within the gold core. Analysis by UV/Vis absorption spectroscopy reveals a concomitant bathochromic shift of the surface plasmon resonance band of the AuNP, indicating that other electronic properties of AuNPs are also affected by the ligand exchange. In total, our results demonstrate that the chemical nature of the ligand controls the valence band structure of AuNPs. PMID- 26274015 TI - Differential Association of Psychosocial Comorbidities With Subclinical Atherosclerosis in Rheumatoid Arthritis. AB - OBJECTIVE: Rheumatoid arthritis (RA) is associated with an elevated risk of cardiovascular disease (CVD) events and subclinical atherosclerosis, but the reasons for the excess risk are unclear. We explored whether psychosocial comorbidities, which may be associated with CVD in the general population, are differentially associated with subclinical atherosclerosis in RA compared to controls. METHODS: Data were from a longitudinal cohort study of 195 RA patients and 1,073 non-RA controls. Using validated scales, heterogeneity in the associations of psychosocial measures (depression, stress, anxiety/anger, support, discrimination/hassles) with measures of subclinical atherosclerosis (coronary artery calcium [CAC] and carotid intima-media thickness [IMT]/plaque) were compared in RA and non-RA groups using multivariable generalized linear models. Computed tomography and ultrasound were used to identify CAC and IMT/plaque, respectively. CAC >100 units was used to define moderate/severe CAC. RESULTS: In RA, per-unit higher anxiety scores (odds ratio [OR] 1.10, P = 0.029), anger scores (OR 1.14, P = 0.037), depressive symptoms (OR 3.41, P = 0.032), and caregiver stress (OR 2.86, P = 0.014) were associated with increased odds of CAC >100 units after adjustment for relevant covariates. These findings persisted despite adjustment for markers of inflammation (C-reactive protein and interleukin-6 levels) and were seen only in RA, not in controls (adjusted multiplicative interaction P = 0.001-0.077). In RA, job stress was associated with an increased risk of carotid plaque (adjusted OR = 3.21, P = 0.019), and increasing social support was associated with lower internal carotid IMT (adjusted P = 0.024). CONCLUSION: Depressive symptoms, stress, anger/anxiety, and social support may preferentially affect CVD risk in RA, and screening/treatment for psychosocial morbidities in RA may help ameliorate the additional CVD burden. PMID- 26274016 TI - Genetic and chromosomal alterations in Kenyan Wilms Tumor. AB - Wilms tumor (WT) is the most common childhood kidney cancer worldwide and poses a cancer health disparity to black children of sub-Saharan African ancestry. Although overall survival from WT at 5 years exceeds 90% in developed countries, this pediatric cancer is alarmingly lethal in sub-Saharan Africa and specifically in Kenya (36% survival at 2 years). Although multiple barriers to adequate WT therapy contribute to this dismal outcome, we hypothesized that a uniquely aggressive and treatment-resistant biology compromises survival further. To explore the biologic composition of Kenyan WT (KWT), we completed a next generation sequencing analysis targeting 10 WT-associated genes and evaluated whole-genome copy number variation. The study cohort was comprised of 44 KWT patients and their specimens. Fourteen children are confirmed dead at 2 years and 11 remain lost to follow-up despite multiple tracing attempts. TP53 was mutated most commonly in 11 KWT specimens (25%), CTNNB1 in 10 (23%), MYCN in 8 (18%), AMER1 in 5 (11%), WT1 and TOP2A in 4 (9%), and IGF2 in 3 (7%). Loss of heterozygosity (LOH) at 17p, which covers TP53, was detected in 18% of specimens examined. Copy number gain at 1q, a poor prognostic indicator of WT biology in developed countries, was detected in 32% of KWT analyzed, and 89% of these children are deceased. Similarly, LOH at 11q was detected in 32% of KWT, and 80% of these patients are deceased. From this genomic analysis, KWT biology appears uniquely aggressive and treatment-resistant. PMID- 26274017 TI - Concentrations of serum amyloid A and plasma fibrinogen in horses undergoing emergency abdominal surgery. AB - OBJECTIVE: To compare the perioperative response of serum amyloid A (SAA) to fibrinogen in horses requiring exploratory celiotomy for colic and to determine if SAA could be used to predict complications and outcome. DESIGN: Prospective observational clinical study. SETTING: University teaching hospital. ANIMALS: Eighteen horses undergoing exploratory celiotomy for colic. Inclusion criteria for the study included survival and anesthetic recovery from exploratory celiotomy, no history of surgery within the past year. INTERVENTIONS: Blood was obtained via jugular venipuncture before surgery (time 0) and at 24, 48, 72, and 96 hours after recovery from anesthesia. MEASUREMENTS AND MAIN RESULTS: Quantitative and semiquantitative fibrinogen, SAA, total nucleated cell counts, and total protein were evaluated at each time point. Multivariable linear regression was used to assess differences at each time point and after grouping horses according to duration of colic prior to surgery, strangulating surgical lesion or not, presence of systemic inflammatory response syndrome (SIRS) on admission, and postsurgical complications. Significant (P < 0.05) increases in SAA concentrations occurred in all cases after surgery compared to fibrinogen concentration, which only demonstrated a mild, clinically insignificant increase postsurgery. SAA concentrations were also significantly increased (P < 0.05) in cases identified with SIRS prior to surgery and postoperatively at 48 (P = 0.05) and 72 hours (P = 0.02) in horses that developed complications. CONCLUSIONS: Measurement of SAA is a more sensitive indicator of inflammation than fibrinogen in the perioperative period of horses requiring exploratory celiotomy for colic. Serial measurement of SAA at 48, 72, and 96 hours after surgery may be helpful to determine risk of complications and guide postoperative management. Measurement of SAA on admission also allows for quantification of SIRS when it is detected clinically. PMID- 26274019 TI - Thrombotic thrombocytopenic purpura in a postoperative patient taking cephalexin responding to plasmapheresis: A case report and review of cephalosporin-induced TTP. AB - The clinical presentation of thrombotic thrombocytopenic purpura (TTP) is often atypical delaying diagnosis and treatment. A number of drugs have been implicated in the development of TTP, including cyclosporine, tacrolimus, clopidogrel, and quinine. To our knowledge, only three cases of cephalosporin-induced TTP have been described, with two of these cases occurring with these use of cephalexin. We herein describe a case of TTP occurring in a postoperative patient taking cephalexin, requiring plasmapheresis. Following plasmapheresis, the patient's mental status and platelet count significantly improved. J. Clin. Apheresis 31:473-475, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26274018 TI - Mapping cell populations in flow cytometry data for cross-sample comparison using the Friedman-Rafsky test statistic as a distance measure. AB - Flow cytometry (FCM) is a fluorescence-based single-cell experimental technology that is routinely applied in biomedical research for identifying cellular biomarkers of normal physiological responses and abnormal disease states. While many computational methods have been developed that focus on identifying cell populations in individual FCM samples, very few have addressed how the identified cell populations can be matched across samples for comparative analysis. This article presents FlowMap-FR, a novel method for cell population mapping across FCM samples. FlowMap-FR is based on the Friedman-Rafsky nonparametric test statistic (FR statistic), which quantifies the equivalence of multivariate distributions. As applied to FCM data by FlowMap-FR, the FR statistic objectively quantifies the similarity between cell populations based on the shapes, sizes, and positions of fluorescence data distributions in the multidimensional feature space. To test and evaluate the performance of FlowMap-FR, we simulated the kinds of biological and technical sample variations that are commonly observed in FCM data. The results show that FlowMap-FR is able to effectively identify equivalent cell populations between samples under scenarios of proportion differences and modest position shifts. As a statistical test, FlowMap-FR can be used to determine whether the expression of a cellular marker is statistically different between two cell populations, suggesting candidates for new cellular phenotypes by providing an objective statistical measure. In addition, FlowMap-FR can indicate situations in which inappropriate splitting or merging of cell populations has occurred during gating procedures. We compared the FR statistic with the symmetric version of Kullback-Leibler divergence measure used in a previous population matching method with both simulated and real data. The FR statistic outperforms the symmetric version of KL-distance in distinguishing equivalent from nonequivalent cell populations. FlowMap-FR was also employed as a distance metric to match cell populations delineated by manual gating across 30 FCM samples from a benchmark FlowCAP data set. An F-measure of 0.88 was obtained, indicating high precision and recall of the FR-based population matching results. FlowMap-FR has been implemented as a standalone R/Bioconductor package so that it can be easily incorporated into current FCM data analytical workflows. PMID- 26274020 TI - Proton-Conducting Magnetic Coordination Polymers. AB - Three isostructural lanthanide-based two- dimensional coordination polymers (CPs) {[Ln2(L)3(H2O)2]n?2n CH3OH)?2n H2O} (Ln=Gd(3+) (1), Tb(3+) (2), Dy(3+) (3); H2L=cyclobutane-1,1-dicarboxylic acid) were synthesized by using a low molecular weight dicarboxylate ligand and characterized. Single-crystal structure analysis showed that in complexes 1-3 lanthanide centers are connected by MU3-bridging cyclobutanedicarboxylate ligands along the c axis to form a rod-shaped infinite 1D coordination chain, which is further linked with nearby chains by MU4 connected cyclobutanedicarboxylate ligands to form 2D CPs in the bc plane. Viewing the packing of the complexes down the b axis reveals that the lattice methanol molecules are located in the interlayer space between the adjacent 2D layers and form H-bonds with lattice and coordinated water molecules to form 1D chains. Magnetic properties of complexes 1-3 were thoroughly investigated. Complex 1 exhibits dominant ferromagnetic interaction between two nearby gadolinium centers and also acts as a cryogenic magnetic refrigerant having a significant magnetic entropy change of -DeltaSm=32.8 J kg(-1) K(-1) for DeltaH=7 T at 4 K (calculated from isothermal magnetization data). Complex 3 shows slow relaxation of magnetization below 10 K. Impedance analysis revealed that the complexes show humidity-dependent proton conductivity (sigma=1.5*10(-5) S cm(-1) for 1, sigma=2.07*10(-4) S cm(-1) for 2, and sigma=1.1*10(-3) S cm(-1) for 3) at elevated temperature (>75 degrees C). They retain the conductivity for up to 10 h at high temperature and high humidity. Furthermore, the proton conductivity results were correlated with the number of water molecules from the water-vapor adsorption measurements. Water-vapor adsorption studies showed hysteretic and two step water vapor adsorption (182,000 MUL g(-1) for 1, 184,000 MUL g(-1) for 2, and 1,874,000 MUL g(-1) for 3) in the experimental pressure range. Simulation of water-vapor adsorption by the Monte Carlo method (for 1) confirmed the high density of adsorbed water molecules, preferentially in the interlayer space between the 2D layers. PMID- 26274021 TI - RANDOMIZED CONTROLLED TRIAL ON IRREVERSIBLE ELECTROPORATION FOR LOCALIZED PROSTATE CANCER:FOCAL ABLATION VERSUS EXTENDED ABLATION. PMID- 26274023 TI - Definitive radiotherapy plus regional hyperthermia for high-risk and very high risk prostate carcinoma: Thermal parameters correlated with biochemical relapse free survival. AB - PURPOSE: The aim of this study was to assess the efficacy of definitive radiotherapy (RT) plus regional hyperthermia (HT) and investigate the potential contribution of HT to clinical outcomes in patients with prostate carcinoma. MATERIALS AND METHODS: Following our institution's treatment protocol, HT was combined with RT to improve clinical outcomes in selected patients with high-risk or very high-risk prostate cancer. Data from 82 patients treated with RT plus HT and 64 patients treated with RT alone were retrospectively analysed. RESULTS: Median follow-up duration was 61 months. The 5-year biochemical disease-free survival (bDFS) rate for the 82 patients treated with RT plus HT was 78%, whereas bDFS for the 64 patients treated with RT alone was 72%; this difference was not significant. Among the 75 patients treated with RT plus HT who underwent intra rectal temperature measurements, higher thermal parameters were significant prognostic indicators of improved bDFS by univariate analysis. A higher CEM43 degrees CT90 thermal parameter and a T stage of T1-2 were significant prognostic factors based on multivariate analysis. The 5-year bDFS rates for the 40 patients with a higher CEM43 degrees CT90 and the 64 patients treated with RT alone were significantly different, whereas 5-year bDFS for the 35 patients with a lower CEM43 degrees CT90 and the 64 patients treated with RT alone were not. CONCLUSIONS: The addition of HT with higher thermal parameters to RT may improve bDFS for patients with high-risk or very high-risk prostate cancer. These findings also demonstrate the importance of careful selection of treatable patients with higher thermal parameters. PMID- 26274022 TI - A Type III protein-RNA toxin-antitoxin system from Bacillus thuringiensis promotes plasmid retention during spore development. AB - Members of the Bacillus cereus sensu lato group of bacteria often contain multiple large plasmids, including those encoding virulence factors in B. anthracis. Bacillus species can develop into spores in response to stress. During sporulation the genomic content of the cell is heavily compressed, which could result in counterselection of extrachromosomal genomic elements, unless they have robust stabilization and segregation systems. Toxin-antitoxin (TA) systems are near-ubiquitous in prokaryotes and have multiple biological roles, including plasmid stabilization during vegetative growth. Here, we have shown that a Type III TA system, based on an RNA antitoxin and endoribonuclease toxin, from plasmid pAW63 in Bacillus thuringiensis serovar kurstaki HD-73 can dramatically promote plasmid retention in populations undergoing sporulation and germination, and we provide evidence that this occurs through the post-segregational killing of plasmid-free forespores. Our findings show how an extremely common genetic module can be used to ensure plasmid maintenance during stress-induced developmental transitions, with implications for plasmid dynamics in B. cereus s.l. bacteria. PMID- 26274024 TI - How motor practice shapes memory: retrieval but not extra study can cause forgetting. AB - We investigated the retrieval specificity of retrieval-induced forgetting (RIF) of motor sequences. In two experiments, participants learned sequential finger movements, each consisting of the movement of two fingers of either the left or the right hand. In the learning phase, these motor sequences were graphically presented and were to be learned as responses to simultaneously presented letter stimuli. Subsequently, participants selectively practiced half the items of one hand. A final recall test then assessed memory for all initially learned items. We contrasted different kinds of selective practice with each other. Whereas retrieval practice required retrieving motor sequences in response to letter stimuli from the learning phase, extra study was an extension of the learning phase, that is, participants performed motor sequences in response to the same animation graphic display as in the learning phase again accompanied by the letter stimulus. All practice conditions strengthened the practiced items, but only retrieval practice resulted in RIF. Thus, the strengthening of items through practice did not suffice to induce forgetting of related motor sequences. Retrieval was a necessary component for practice to shape memory for body movements by impairing the subsequent recall of motor sequences that were related to the practiced motor sequences. PMID- 26274025 TI - Membrane-Coupled mRNA Trafficking in Fungi. AB - Intracellular logistics are essential for delivery of newly synthesized material during polar growth of fungal hyphae. Proteins and lipids are actively transported throughout the cell by motor-dependent movement of small vesicles or larger units such as endosomes and the endoplasmic reticulum. A remarkably tight link is emerging between active membrane trafficking and mRNA transport, a process that determines the precise subcellular localization of translation products within the cell. Here, we report on recent insights into the mechanism and biological role of these intricate cotransport processes in fungal models such as Saccharomyces cerevisiae, Candida albicans, and Ustilago maydis. In the latter, we focus on the new finding of endosomal mRNA transport and its implications for protein targeting, complex assembly, and septin biology. PMID- 26274026 TI - Microbiology Meets Big Data: The Case of Gut Microbiota-Derived Trimethylamine. AB - During the past decade, meta-omics approaches have revolutionized microbiology, allowing for a cultivation-free assessment of the composition and functional properties of entire microbial ecosystems. On the one hand, a phylogenetic and functional interpretation of such data relies on accumulated genetic, biochemical, metabolic, and phenotypic characterization of microbial variation. On the other hand, the increasing availability of extensive microbiome data sets and corresponding metadata provides a vast, underused resource for the microbiology field as a whole. To demonstrate the potential for integrating big data into a functional microbiology workflow, we review literature on trimethylamine (TMA), a microbiota-generated metabolite linked to atherosclerosis development. Translating recently elucidated microbial pathways resulting in TMA production into genomic orthologs, we demonstrate how to mine for their presence in public (meta-) genomic databases and link findings to associated metadata. Reviewing pathway abundance in public data sets shows that TMA production potential is associated with symptomatic atherosclerosis and allows identification of currently uncharacterized TMA-producing bacteria. PMID- 26274027 TI - PSF/SFPQ is a very common gene fusion partner in TFE3 rearrangement-associated perivascular epithelioid cell tumors (PEComas) and melanotic Xp11 translocation renal cancers: clinicopathologic, immunohistochemical, and molecular characteristics suggesting classification as a distinct entity. AB - An increasing number of TFE3 rearrangement-associated tumors, such as TFE3 rearrangement-associated perivascular epithelioid cell tumors (PEComas), melanotic Xp11 translocation renal cancers, and melanotic Xp11 neoplasms, have recently been reported. We examined 12 such cases, including 5 TFE3 rearrangement associated PEComas located in the pancreas, cervix, or pelvis and 7 melanotic Xp11 translocation renal cancers, using clinicopathologic, immunohistochemical, and molecular analyses. All the tumors shared a similar morphology, including a purely nested or sheet-like architecture separated by a delicate vascular network, purely epithelioid cells displaying a clear or granular eosinophilic cytoplasm, a lack of papillary structures and spindle cell or fat components, uniform round or oval nuclei containing small visible nucleoli, and, in most cases (11/12), melanin pigmentation. The levels of mitotic activity and necrosis varied. All 12 cases displayed moderately (2+) or strongly (3+) positive immunoreactivity for TFE3 and cathepsin K. One case labeled focally for HMB45 and Melan-A, whereas the others typically labeled moderately (2+) or strongly (3+) for 1 of these markers. None of the cases were immunoreactive for smooth muscle actin, desmin, CKpan, S100, or PAX8. PSF-TFE3 fusion genes were confirmed by reverse transcription polymerase chain reaction in cases (7/7) in which a novel PSF-TFE3 fusion point was identified. All of the cases displayed TFE3 rearrangement associated with Xp11 translocation. Furthermore, we developed a PSF TFE3 fusion fluorescence in situ hybridization assay for the detection of the PSF TFE3 fusion gene and detected it in all 12 cases. Clinical follow-up data were available for 7 patients. Three patients died, and 2 patients (cases 1 and 3) remained alive with no evidence of disease after initial resection. Case 2 experienced recurrence and remained alive with disease. Case 5, a recent case, remained alive with extensive abdominal cavity metastases. Our data suggest that these tumors belong to a single clinicopathologic spectrum and expand the known characteristics of TFE3 rearrangement-associated tumors. PMID- 26274028 TI - Prostate biopsy and radical prostatectomy Gleason score correlation in heterogenous tumors: proposal for a composite Gleason score. AB - When prostate biopsy cores are separately identified in multiple containers, current recommendations are to grade each specimen individually. For treatment algorithms, the highest Gleason score (HGS) is typically used as the overall score, even if a lower score predominates. This practice has the potential to misrepresent the overall cancer in the entire gland for some patients and place them in a higher-grade group. We compare a novel composite Gleason score (CGS), integrating grade patterns from contiguous positive biopsy sites, with HGS to determine correlation with the radical prostatectomy (RP) Gleason score (GS). One hundred needle biopsy cases from 2008 to 2012 with >2 GSs in a biopsy set (eg, 3+3=6, 3+4=7, and 4+3=7) or more than a 1-step difference in GS (eg, 3+4=7 and 4+4=8 without 4+3=7) were analyzed. Grades were assigned using both methods (HGS and CGS) and compared with RPGS. Grade groups I to V were used to define downgrade and upgrade. Comparing HGS with RPGS, 31% remained the same and 69% had a change in GS (87% downgraded and 13% upgraded). Comparing CGS with RPGS, 59% remained the same and 41% had a change in GS (10% downgraded and 90% upgraded). Of the 2 methods, the CGS showed better overall correlation with RP (P<0.001) and was less likely to be downgraded compared with HGS. CGS correlates better with RPGS than HGS when >2 grades are present in a biopsy set. CGS has a significantly lower rate of downgrade and predicts the RPGS more accurately than HGS. PMID- 26274030 TI - GATA3 immunohistochemistry expression in histologic subtypes of primary breast carcinoma and metastatic breast carcinoma cytology. AB - GATA3 plays a role in cell proliferation and differentiation in many tissues, including breast, and it has been suggested that GATA3 expression correlates with ER expression. However, little is known on GATA3 expression in various subtypes of breast carcinoma, its utilization in cytology, and on how GATA3 performs in comparison with GCDFP-15 and mammaglobin. Eighty-four histology cases of breast carcinoma of various subtypes, including 28 triple-negative breast carcinomas, along with 20 cytology cases of metastatic breast carcinoma and 12 cytology cases of ER-positive metastatic gynecologic malignancies, were stained for GATA3, GCDFP 15, and mammaglobin. In non-triple-negative breast carcinomas (n=56), GATA3 showed 100% sensitivity, higher than GCDFP-15 (42.8%; P<0.0001) and mammaglobin (58.9%; P<0.0001), whereas staining patterns were similar for all the histologic subtypes examined. Staining scores were determined by multiplying the percentage of cancer cells staining with an intensity score of 1+, 2+, or 3+ (range, 0 to 300). In non-triple-negative carcinomas, GATA3 showed a mean score of 273.7, higher than GCDFP-15 (107.5; P<0.0001) and mammaglobin (147.7; P<0.0001). In triple-negative breast carcinomas (n=28), GATA3 showed a sensitivity of 60.7%, greater than GCDFP-15 (17.9%; P=0.0022) and mammaglobin (7.1%; P<0.0001). These results were consistent irrespective of the subtype examined. In breast carcinoma cytology cases, 100% stained with GATA3, higher than GCDFP-15 (20%; P<0.0001) and mammaglobin (45%; P<0.0001). None of the metastatic endometrial or ovarian carcinomas were positive for GATA3. Although GATA3 expression correlates with ER expression in breast, no correlation is observed in gynecologic malignancies. Thus, in working up ER-positive metastatic malignancies GATA3 demonstrates specificity for breast. PMID- 26274029 TI - A fibromyxoid stromal response is associated with an infiltrative tumor morphology, perineural invasion, and lymph node metastasis in squamous cell carcinoma of the vulva. AB - Patterns of invasion and stromal response are understudied in vulvar squamous cell carcinoma. The aim of this study was to explore whether histologic features such as an infiltrative pattern of invasion and fibromyxoid stromal response (FMX SR) are meaningful prognostic factors. We reviewed 143 vulvar squamous cell carcinoma resections and correlated patterns of invasion and stromal response with patient age, ethnicity, depth of invasion, tumor size, perineural invasion (S100/AE1/3 stain), lymph node involvement (LNI), extranodal extension, margin status, pathologic stage, and recurrence. Univariate analyses of continuous variables were performed using t tests, whereas Pearson chi tests were used for categorical variables. Logistic regression analyses examined the relationship between histopathologic characteristics and clinical outcomes. There was a statistically significant association between infiltrative tumors and an FMX-SR in comparison with noninfiltrative tumors (P<0.001). Tumors with FMX-SR were significantly more deeply invasive (P=0.0025) and more likely to have LNI (P=0.0364), extranodal extension (P=0.0227), and perineural invasion (P=0.0011) compared with tumors without FMX-SR. For cases with negative surgical margins, the association between tumors with FMX-SR and LNI was significantly strengthened (odds ratio=4.73, P=0.0042), even after adjustments for age, race, and depth of invasion (odds ratio=4.34, P=0.0154). The presence of both FMX-SR and an infiltrative pattern of invasion in tumors with negative margins was significantly associated with LNI (P=0.0235) and recurrence (P=0.0124). These results suggest that interactions between nerve, tumor, and stromal cells play a role in tumor progression and represent additional prognostic factors that help stratify those patients at highest risk for LNI, extranodal extension, and recurrence. PMID- 26274031 TI - Simultaneous occurrence of focal nodular hyperplasia and HNF1A-inactivated hepatocellular adenoma: a collision tumor simulating a composite FNH-HCA. AB - Mixed focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) within a single tumor mass is rarely reported, and most of these cases are examples of tumors with features intermediate between FNH and HCA. Although a few reported cases are probably examples of true mixed tumors, none was evaluated immunohistochemically or confirmed by molecular analysis. We report a mixed FNH and HCA arising in a woman with several HNF1A-inactivated adenomas. Our case is the first case of mixed FNH and HNF1A-inactivated HCA documented by immunohistochemistry. PMID- 26274032 TI - Application of BRAF V600E mutation analysis for the diagnosis of metanephric adenofibroma. PMID- 26274033 TI - The 5-Year EFS of Multisystem LCH With Risk-Organ Involvement Is Suboptimal: A Single-center Experience From India. AB - The study describes an 8-year experience of a single center in managing patients with langerhans cell histiocytosis on the basis of the langerhans cell histiocytosis-III platform. A retrospective case-file review of children diagnosed during 2006 to 2013 was performed. Group 1 (multisystem with risk-organ involvement) patients received an initial treatment of 6 to 12 weeks, followed by continuation treatment to complete 12 months. Drugs included vinblastine, prednisolone, and 6-mercaptopurine. Group 2 (multisystem without risk-organ involvement) patients received a similar treatment, except for 6-mercaptopurine. Group 3 (single-system/multifocal bone disease) patients were treated for a duration of 6 months. Forty-nine patients were treated: 24 (49%), 14 (28.6%), and 11 (22.4%) in groups 1, 2, and 3, respectively. The mean age at diagnosis was 31.6 +/- 28.4 months (range, 4 to 120 mo). Five patients abandoned treatment. There were 7 deaths, all in group 1. All patients who died had either a partial response or progressive disease after induction (P=0.000). Among patients with liver involvement, those with sclerosing cholangitis had a greater mortality (P=0.007). A relapse was observed in 12 (24.5%) patients. The frequency of relapse was not different in the 3 groups (P=0.833). The 5-year event-free survival in groups 1, 2, and 3 was 29.3 +/- 10%, 58.9 +/- 14.6%, and 69.3 +/- 15%, respectively (P=0.019). The 5-year overall survival was 100% in groups 2/3 and 68.9 +/- 9.8% in group 1 (P=0.011). PMID- 26274034 TI - Bacillus cereus Cerebral Abscess During Induction Chemotherapy for Childhood Acute Leukemia. AB - A 5-year-old boy with standard-risk B-cell acute lymphoblastic anemia developed fever during induction chemotherapy. The patient had no neurological symptoms. Blood cultures grew Bacillus cereus and neuroimaging studies demonstrated a cerebral abscess. Imaging changes resolved after completion of antibiotics. Bacillus cereus bacteremia is increasingly implicated as the cause of life threatening infections, including cerebral abscesses, in compromised patients. Positive blood cultures for this organism should prompt neuroimaging and consideration of cerebrospinal fluid sampling, as well as catheter removal. Given the worse outcome with central nervous system involvement, there is a need for increased awareness and early diagnosis, particularly in immunocompromised individuals. PMID- 26274036 TI - Bosentan-induced Reduction in Cyclosporine-A Levels: A Rare Interaction in an Infant With Osteopetrosis and Severe Pulmonary Hyperetension. PMID- 26274037 TI - Management of Acute Myeloblastic Leukemia in a Child With Biallelic Mismatch Repair Deficiency. AB - Germline biallelic mismatch repair deficiency (bMMRD) results in a unique cancer predisposition syndrome in which the affected children are susceptible to the development of malignancies, especially brain, gastrointestinal, and lymphoid cancers. Acute myeloblastic leukemia is rarely reported in this syndrome. Here we report the decision-making challenges in a bMMRD child with acute myeloblastic leukemia. Our experience should alert physicians to include bMMRD in the differential diagnosis of a child with hyper/hypopigmented spots and leukemia. Furthermore, the presence of the above and consanguinity emphasizes the need to rule out bMMRD when an allogeneic bone marrow transplant is considered and to enable the surveillance of other family members for earlier detection of cancers in these children. PMID- 26274038 TI - FUNDUS CHANGES IN BRANCH RETINAL ARTERIOLAR OCCLUSION. AB - PURPOSE: To investigate systematically various fundus changes in branch retinal arteriolar occlusion (BRAO) and their natural history. METHODS: The study comprised a cohort of 123 consecutive patients (135 eyes) with BRAO. Ophthalmic evaluation at initial and follow-up visits included recording visual acuity, visual fields, and detailed anterior segment and fundus examinations, and at initial visit fluorescein fundus angiography. RESULTS: Probability estimates of retinal infarct still present were 89% 1 week after BRAO onset, 69% after 2 weeks, 67% after 3 weeks, 34% after 1 month, and 13% after 3 months. Optic disk pallor in the involved region developed in 21% within 1 month from onset, in 42% by 2 months, and in 65% by 3 months. Retinal arteriolar attenuation developed in 19% within 1 month from onset, and in 28% by 6 months. Arteriolar sheathing developed in 19% within 1 month and 25% within 12 months. Arteriolar emboli were found in 58%; 65% of those were at initial visit, in BRAO seen within 1 week of onset. CONCLUSION: Most common cause of BRAO is embolism from the heart or carotid arteries; emboli usually get impacted at the arteriolar bifurcation. Migration and disappearance of retinal emboli is a common finding. Evolution of the retinal and optic disk changes is described. PMID- 26274039 TI - Manual Removal of Dystrophic Calcifications From Silicone Intraocular Lenses Using a 27-Gauge Nitinol Loop With Concave Tines. PMID- 26274040 TI - Sutureless Iris Repair: Cauterization Technique. PMID- 26274041 TI - Fatty acid amide hydrolase inhibitor URB597 prevented tolerance and cognitive deficits induced by chronic morphine administration in rats. AB - Inhibitors of the endocannabinoid metabolic enzyme fatty acid amide hydrolase exert therapeutic effects, but might also be associated with some of the adverse effects of cannabis. However, at least one fatty acid amide hydrolase inhibitor, URB597, has beneficial effects without signs of abuse or dependence. Although previous investigations have evaluated URB597-morphine interactions, the effects of URB597 on morphine tolerance and cognition deficits have not been studied previously. Rats were rendered tolerant to or dependent on morphine by an injection of morphine (10 mg/kg, subcutaneous) twice daily, respectively, for 7 or 10 days. URB597 (1 mg/kg, intraperitoneal) was administered before morphine. The tail-flick and passive avoidance learning tests were used to evaluate tolerance and cognition. Chronic morphine injection led to significant tolerance to the antinociceptive effect on days 5 and 7. URB597 completely prevented the development of morphine tolerance. URB597 also enhanced memory acquisition in the passive avoidance learning test, and although morphine impaired memory, URB597 alleviated this effect. These data show that URB597 protects against tolerance and memory deficits in chronic usage of morphine and suggests URB597 as a promising candidate for the treatment of adverse effects of opioids. PMID- 26274042 TI - Role of thermo TRPA1 and TRPV1 channels in heat, cold, and mechanical nociception of rats. AB - A sensitive response of the nervous system to changes in temperature is of predominant importance for homeotherms to maintain a stable body temperature. A number of temperature-sensitive transient receptor potential (TRP) ion channels have been studied as nociceptors that respond to extreme temperatures and harmful chemicals. Recent findings in the field of pain have established a family of six thermo-TRP channels (TRPA1, TRPM8, TRPV1, TRPV2, TRPV3, and TRPV4) that exhibit sensitivity to increases or decreases in temperature, as well as to chemical substances eliciting the respective hot or cold sensations. In this study, we used behavioral methods to investigate whether mustard oil (allyl isothiocyanate) and capsaicin affect the sensitivity to heat, innocuous and noxious cold, and mechanical stimuli in male rats. The results obtained indicate that TRPA1 and TRPV1 channels are clearly involved in pain reactions, and the TRPA1 agonist allyl isothiocyanate enhances the heat pain sensitivity, possibly by indirectly modulating TRPV1 channels coexpressed in nociceptors with TRPA1. Overall, our data support the role of thermosensitive TRPA1 and TRPV1 channels in pain modulation and show that these two thermoreceptor channels are in a synergistic and/or conditional relationship with noxious heat and cold cutaneous stimulation. PMID- 26274043 TI - Use of an operant paradigm for the study of antidepressant-induced sexual dysfunction. AB - These studies were designed to develop a paradigm for the detection of antidepressant-induced sexual dysfunction in female rats. Ovariectomized, Fischer rats were conditioned to nose poke to open a guillotine door to gain access to a sexually active male. To develop the procedure, we examined the acquisition and stability of the response with a 15-s fixed interval, compared rats treated with 10 MUg estradiol benzoate and 500 MUg progesterone with those that received only estradiol benzoate, and carried out a preliminary analysis of the effects of 5, 10, and 15 mg/kg fluoxetine. We then more fully evaluated the effects of 5 mg/kg fluoxetine. Fluoxetine reduced sexual motivation, as assessed by the number of nose pokes, the number of nose poke episodes, and the latency to approach the male. In addition, changes in the females' sexual motivation were examined before and after ejaculation during the final conditioning trials. The number of nose pokes was reduced and the latency to initiate a new nose poke episode was increased following ejaculation. The robustness of the antidepressant-induced decline in sexual motivation is in marked contrast to the findings with several other animal models for sexual dysfunction and illustrates the usefulness of the operant procedure. PMID- 26274044 TI - Pregnancy Outcomes Following In Utero Exposure to Second-Generation Antipsychotics: A Systematic Review and Meta-Analysis. AB - Second-generation antipsychotics (SGAs) are increasingly used for a variety of mental illnesses; however, the data regarding the safety of these medications during pregnancy are inconclusive and contradictory. We examined the risk of adverse pregnancy outcomes associated with in utero exposure to SGAs by conducting a systematic review and meta-analysis. We searched the databases EMBASE and MEDLINE from January 1990 to December 2014. Eligible studies had to report pregnant women who took SGAs during pregnancy (first trimester exposure if analyzing congenital malformations), follow a healthy comparison group in a similar manner, and report data on pregnancy outcomes. There was no restriction on language, sample size, or publication date. The primary outcome analyzed was major congenital malformations, and secondary outcomes included miscarriages, stillbirths, preterm births, small or large for gestational age neonates, and differences in gestational ages and birth weights. A total of 12 studies met our inclusion criteria, totalling 1782 cases and 1,322,749 controls. The use of SGA during the first trimester of pregnancy was associated with a significant increased risk for major congenital malformations (odds ratio, 2.03; 95% confidence interval, 1.41-2.93); however, no specific pattern of malformations was found. An increased risk was also found for preterm births (odds ratio, 1.85; 95% CI, 1.20-2.86). The use of SGA during pregnancy was not found to be associated with an increased risk for secondary outcomes analyzed. The absence of a specific pattern of malformations makes it difficult to identify an explicit risk posed by SGAs, and therefore, further studies sufficiently controlling for confounding factors are needed to validate these findings. PMID- 26274045 TI - Metabolic Impairments Precede Changes in Hunger and Food Intake Following Short Term Administration of Second-Generation Antipsychotics. AB - The second-generation antipsychotics (SGAs) are associated with weight gain and an increased incidence of metabolic diseases. The metabolic impairments are assumed a consequence of increased body adiposity secondary to central nervous system-associated increases in food intake. We have previously reported that, independent of weight gain, 9 days of olanzapine administration to control subjects is associated with insulin resistance and increases in postprandial levels of insulin and glucagon-like peptide 1 to a mixed meal challenge. This current report describes previously unpublished data on the effects of the SGAs olanzapine and aripiprazole compared with placebo on detailed hunger and satiety responses over the 12-day inpatient evaluation as well as postprandial ghrelin and leptin responses prior to and following administration of the 2 SGAs. We found no changes in hunger, fullness, or in the orexigenic hormone ghrelin or satiety hormone leptin, consistent with our previous report indicating no change in weight during this study. The results indicate that the SGAs are associated with metabolic changes prior to changes in hunger, satiety, and food intake, and this temporal separation suggests that there are differential mechanisms mediating SGA-associated changes in metabolism and food intake. PMID- 26274046 TI - Interactions of hyaluronan grafted on protein surfaces studied using a quartz crystal microbalance and a surface force balance. AB - Vocal folds are complex and multilayer-structured where the main layer is widely composed of hyaluronan (HA). The viscoelasticity of HA is key to voice production in the vocal fold as it affects the initiation and maintenance of phonation. In this study a simple layer-structured surface model was set up to mimic the structure of the vocal folds. The interactions between two opposing surfaces bearing HA were measured and characterised to analyse HA's response to the normal and shear compression at a stress level similar to that in the vocal fold. From the measurements of the quartz crystal microbalance, atomic force microscopy and the surface force balance, the osmotic pressure, normal interactions, elasticity change, volume fraction, refractive index and friction of both HA and the supporting protein layer were obtained. These findings may shed light on the physical mechanism of HA function in the vocal fold and the specific role of HA as an important component in the effective treatment of the vocal fold disease. PMID- 26274048 TI - Geometrical and morphological optimizations of plasmonic nanoarrays for high performance SERS detection. AB - Here we present an in-depth and comprehensive study of the effect of the geometry and morphology of nanoarray (NA) substrates on their surface-enhanced Raman scattering (SERS) performance. The high-quality SERS-active NA substrates of various unit shapes and pitches are assembled through electron beam lithography and fabricated by electron beam physical vapor deposition. Good agreement is found on comparing the Raman scattering results with the integrals of the fourth power of local electric fields from the three-dimensional numerical simulations. A novel type of hybrid NA substrate composed of disordered nanoparticles and a periodic NA is fabricated and characterized. The morphology of NAs has little influence on the SERS performance of hybrid NA substrates and they perform better than both their counterparts pure NA and disordered nanoparticle substrates. PMID- 26274047 TI - Flow Cytometry Reveals Similarities Between Lung Macrophages in Humans and Mice. PMID- 26274049 TI - Long-term effects of timber harvesting on hemicellulolytic microbial populations in coniferous forest soils. AB - Forest ecosystems need to be sustainably managed, as they are major reservoirs of biodiversity, provide important economic resources and modulate global climate. We have a poor knowledge of populations responsible for key biomass degradation processes in forest soils and the effects of forest harvesting on these populations. Here, we investigated the effects of three timber-harvesting methods, varying in the degree of organic matter removal, on putatively hemicellulolytic bacterial and fungal populations 10 or more years after harvesting and replanting. We used stable-isotope probing to identify populations that incorporated (13)C from labeled hemicellulose, analyzing (13)C-enriched phospholipid fatty acids, bacterial 16 S rRNA genes and fungal ITS regions. In soil microcosms, we identified 104 bacterial and 52 fungal hemicellulolytic operational taxonomic units (OTUs). Several of these OTUs are affiliated with taxa not previously reported to degrade hemicellulose, including the bacterial genera Methylibium, Pelomonas and Rhodoferax, and the fungal genera Cladosporium, Pseudeurotiaceae, Capronia, Xenopolyscytalum and Venturia. The effect of harvesting on hemicellulolytic populations was evaluated based on in situ bacterial and fungal OTUs. Harvesting treatments had significant but modest long term effects on relative abundances of hemicellulolytic populations, which differed in strength between two ecozones and between soil layers. For soils incubated in microcosms, prior harvesting treatments did not affect the rate of incorporation of hemicellulose carbon into microbial biomass. In six ecozones across North America, distributions of the bacterial hemicellulolytic OTUs were similar, whereas distributions of fungal ones differed. Our work demonstrates that diverse taxa in soil are hemicellulolytic, many of which are differentially affected by the impact of harvesting on environmental conditions. However, the hemicellulolytic capacity of soil communities appears resilient. PMID- 26274051 TI - A model for ultra-fast charge transport in membrane proteins. AB - Isolated proteins have recently been observed to transport charge and reactivity over very long distances with extraordinary rates and near perfect efficiencies in spite of their site. This is not the case if the peptide is in water, where the efficiency of charge hopping to the next site is reduced to approximately 2%. Here, water is not an ideal solvent for charge transport. The issue at hand is how to explain such enormous charge transfer quenching in water compared to another typical medium, namely lipid. We performed molecular dynamics simulations to computationally substantiate the novel long-distance charge transfer yield of the polypeptides in lipids. This is characterized by the charge transfer persistent-distance decay constant and not by the rate, which is seldom, if ever, measured and hence not directly addressed here. This model can encompass an extremely wide range of yields over very long distances in peptides in various media. The calculations here demonstrate the good charge transport efficiency in lipids in contrast to the poor efficiency in water. The protein charge transport also exhibits a very strong anisotropic effect in lipids. The peptide secondary structure effect of charge transfer in membranes is analyzed in contrast to that in water. These results suggest that this model can be useful for the prediction of charge transfer efficiency in various environments of interest and indicate that the charge transfer is highly efficient in membrane proteins. PMID- 26274050 TI - Prolonged antibiotic treatment induces a diabetogenic intestinal microbiome that accelerates diabetes in NOD mice. AB - Accumulating evidence supports that the intestinal microbiome is involved in Type 1 diabetes (T1D) pathogenesis through the gut-pancreas nexus. Our aim was to determine whether the intestinal microbiota in the non-obese diabetic (NOD) mouse model played a role in T1D through the gut. To examine the effect of the intestinal microbiota on T1D onset, we manipulated gut microbes by: (1) the fecal transplantation between non-obese diabetic (NOD) and resistant (NOR) mice and (2) the oral antibiotic and probiotic treatment of NOD mice. We monitored diabetes onset, quantified CD4+T cells in the Peyer's patches, profiled the microbiome and measured fecal short-chain fatty acids (SCFA). The gut microbiota from NOD mice harbored more pathobionts and fewer beneficial microbes in comparison with NOR mice. Fecal transplantation of NOD microbes induced insulitis in NOR hosts suggesting that the NOD microbiome is diabetogenic. Moreover, antibiotic exposure accelerated diabetes onset in NOD mice accompanied by increased T-helper type 1 (Th1) and reduced Th17 cells in the intestinal lymphoid tissues. The diabetogenic microbiome was characterized by a metagenome altered in several metabolic gene clusters. Furthermore, diabetes susceptibility correlated with reduced fecal SCFAs. In an attempt to correct the diabetogenic microbiome, we administered VLS#3 probiotics to NOD mice but found that VSL#3 colonized the intestine poorly and did not delay diabetes. We conclude that NOD mice harbor gut microbes that induce diabetes and that their diabetogenic microbiome can be amplified early in life through antibiotic exposure. Protective microbes like VSL#3 are insufficient to overcome the effects of a diabetogenic microbiome. PMID- 26274052 TI - Direct Mouse Trauma/Burn Model of Heterotopic Ossification. AB - Heterotopic ossification (HO) is the formation of bone outside of the skeleton which forms following major trauma, burn injuries, and orthopaedic surgical procedures. The majority of animal models used to study HO rely on the application of exogenous substances, such as bone morphogenetic protein (BMP), exogenous cell constructs, or genetic mutations in BMP signaling. While these models are useful they do not accurately reproduce the inflammatory states that cause the majority of cases of HO. Here we describe a burn/tenotomy model in mice that reliably produces focused HO. This protocol involves creating a 30% total body surface area partial thickness contact burn on the dorsal skin as well as division of the Achilles tendon at its midpoint. Relying solely on traumatic injury to induce HO at a predictable location allows for time-course study of endochondral heterotopic bone formation from intrinsic physiologic processes and environment only. This method could prove instrumental in understanding the inflammatory and osteogenic pathways involved in trauma-induced HO. Furthermore, because HO develops in a predictable location and time-course in this model, it allows for research to improve early imaging strategies and treatment modalities to prevent HO formation. PMID- 26274053 TI - Generation and Quantitative Analysis of Pulsed Low Frequency Ultrasound to Determine the Sonic Sensitivity of Untreated and Treated Neoplastic Cells. AB - Low frequency ultrasound in the 20 to 60 kHz range is a novel physical modality by which to induce selective cell lysis and death in neoplastic cells. In addition, this method can be used in combination with specialized agents known as sonosensitizers to increase the extent of preferential damage exerted by ultrasound against neoplastic cells, an approach referred to as sonodynamic therapy (SDT). The methodology for generating and applying low frequency ultrasound in a preclinical in vitro setting is presented to demonstrate that reproducible cell destruction can be attained in order to examine and compare the effects of sonication on neoplastic and normal cells. This offers a means by which to reliably sonicate neoplastic cells at a level of consistency required for preclinical therapeutic assessment. In addition, the effects of cholesterol depleting and cytoskeletal-directed agents on potentiating ultrasonic sensitivity in neoplastic cells are discussed in order to elaborate on mechanisms of action conducive to sonochemotherapeutic approaches. PMID- 26274055 TI - Comprehensive Study on the Controlled Plasmon-Enhanced Photocatalytic Activity of Hybrid Au/ZnO Systems Mediated by Thermoresponsive Polymer Linkers. AB - Hybrid semiconductor/noble metal nanostructures coupled with responsive polymers were used to probe unique plasmon-mediated photocatalytic properties associated with swelling-shrinking transitions in polymer chains triggered by specific external stimuli. Poly(N-isopropylacrylamide) (PNIPAM) brushes were anchored on Au films by atom transfer radical polymerization and ZnO nanoparticles were immobilized on the PNIPAM layer to explore controlled photocatalytic activity. The plasmon-enhanced photocatalytic activity was dictated by two critical parameters, that is, grafting density and molecular weight of PNIPAM involved in Au film-PNIPAM-ZnO. The effect of the areal density of PNIPAM chains on the temperature-responsive UV light photocatalytic activities showed mutually antagonistic trends at two different temperatures. The performance at high density was higher above a lower critical solution temperature (LCST), that is, under contracted configuration, while the sample with low density showed higher activity below LCST, that is, extended configuration. Among all the cases explored, the UV light activity was highest for the sample with thin PNIPAM layer and high density above LCST. The visible light activity was induced only for thin PNIPAM layer and high density, and it was higher above LCST. The efficiency of photocatalytic decomposition of phenol pollutant was dramatically enhanced from 10% to 55% upon the increase in temperature under visible light illumination. PMID- 26274056 TI - Scapulothoracic kinematics during scaption after one year of tennis practice in elite girl players. PMID- 26274054 TI - Fatty acids linked to cardiovascular mortality are associated with risk factors. AB - BACKGROUND: Although saturated fatty acids (FAs) have been linked to cardiovascular mortality, it is not clear whether this outcome is attributable solely to their effects on low-density lipoprotein cholesterol (LDL-C) or whether other risk factors are also associated with FAs. The Western Alaskan Native population, with its rapidly changing lifestyles, shift in diet from unsaturated to saturated fatty acids and dramatic increase in cardiovascular disease (CVD), presents an opportunity to elucidate any associations between specific FAs and known CVD risk factors. OBJECTIVE: We tested the hypothesis that the specific FAs previously identified as related to CVD mortality are also associated with individual CVD risk factors. METHODS: In this community-based, cross-sectional study, relative proportions of FAs in plasma and red blood cell membranes were compared with CVD risk factors in a sample of 758 men and women aged >=35 years. Linear regression analyses were used to analyze relations between specific FAs and CVD risk factors (LDL-C, high-density lipoprotein cholesterol, triglycerides, C-reactive protein, systolic blood pressure, diastolic blood pressure, heart rate, body mass index, fasting glucose and fasting insulin, 2-hour glucose and 2 hour insulin). RESULTS: The specific saturated FAs previously identified as related to CVD mortality, the palmitic and myristic acids, were adversely associated with most CVD risk factors, whereas unsaturated linoleic acid (18:2n 6) and the marine n-3 FAs were not associated or were beneficially associated with CVD risk factors. CONCLUSIONS: The results suggest that CVD risk factors are more extensively affected by individual FAs than hitherto recognized, and that risk for CVD, MI and stroke can be reduced by reducing the intake of palmitate, myristic acid and simple carbohydrates and improved by greater intake of linoleic acid and marine n-3 FAs. PMID- 26274057 TI - Ex Vivo Culture of Pharyngeal Arches to Study Heart and Muscle Progenitors and Their Niche. AB - The pharyngeal mesoderm of developing embryos contributes to broad regions of head and heart musculature. We have developed a novel method to study head and heart progenitor cell development with pharyngeal arches (also known as branchial arches) ex vivo. Using this method, we have recently described that the second pharyngeal arch contains self-renewing heart progenitors and serves as a microenvironment for expansion of the progenitors during mouse heart development. The progenitor cells remain undifferentiated and expansive inside the arch, but quickly become functional cardiomyocytes as they migrate out of the arch. We also reported that first pharyngeal arch contains muscle progenitors giving rise to myotubes after leaving the arch. Here, we demonstrate the procedure for the dissection and ex vivo culture of first and second pharyngeal arches from developing mouse embryos. The method enables one to study head and heart progenitor/muscle development, including cardiomyocyte and myotube formation in detail ex vivo. PMID- 26274058 TI - Synthesis and Catalytic Performance of Gold Intercalated in the Walls of Mesoporous Silica. AB - As a promising catalytically active nano reactor, gold nanoparticles intercalated in mesoporous silica (GMS) were successfully synthesized and properties of the materials were investigated. We used a one pot sol-gel approach to intercalate gold nano particles in the walls of mesoporous silica. To start with the synthesis, P123 was used as template to form micelles. Then TESPTS was used as a surface modification agent to intercalate gold nano particles. Following this process, TEOS was added in as a silica source which underwent a polymerization process in acid environment. After hydrothermal processing and calcination, the final product was acquired. Several techniques were utilized to characterize the porosity, morphology and structure of the gold intercalated mesoporous silica. The results showed a stable structure of mesoporous silica after gold intercalation. Through the oxidation of benzyl alcohol as a benchmark reaction, the GMS materials showed high selectivity and recyclability. PMID- 26274059 TI - High-frequency Ultrasound Imaging of Mouse Cervical Lymph Nodes. AB - High-frequency ultrasound (HFUS) is widely employed as a non-invasive method for imaging internal anatomic structures in experimental small animal systems. HFUS has the ability to detect structures as small as 30 um, a property that has been utilized for visualizing superficial lymph nodes in rodents in brightness (B) mode. Combining power Doppler with B-mode imaging allows for measuring circulatory blood flow within lymph nodes and other organs. While HFUS has been utilized for lymph node imaging in a number of mouse model systems, a detailed protocol describing HFUS imaging and characterization of the cervical lymph nodes in mice has not been reported. Here, we show that HFUS can be adapted to detect and characterize cervical lymph nodes in mice. Combined B-mode and power Doppler imaging can be used to detect increases in blood flow in immunologically-enlarged cervical nodes. We also describe the use of B-mode imaging to conduct fine needle biopsies of cervical lymph nodes to retrieve lymph tissue for histological analysis. Finally, software-aided steps are described to calculate changes in lymph node volume and to visualize changes in lymph node morphology following image reconstruction. The ability to visually monitor changes in cervical lymph node biology over time provides a simple and powerful technique for the non invasive monitoring of cervical lymph node alterations in preclinical mouse models of oral cavity disease. PMID- 26274060 TI - Quantification of Heavy Metals and Other Inorganic Contaminants on the Productivity of Microalgae. AB - Increasing demand for renewable fuels has researchers investigating the feasibility of alternative feedstocks, such as microalgae. Inherent advantages include high potential yield, use of non-arable land and integration with waste streams. The nutrient requirements of a large-scale microalgae production system will require the coupling of cultivation systems with industrial waste resources, such as carbon dioxide from flue gas and nutrients from wastewater. Inorganic contaminants present in these wastes can potentially lead to bioaccumulation in microalgal biomass negatively impact productivity and limiting end use. This study focuses on the experimental evaluation of the impact and the fate of 14 inorganic contaminants (As, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Sb, Se, Sn, V and Zn) on Nannochloropsis salina growth. Microalgae were cultivated in photobioreactors illuminated at 984 umol m(-2) sec(-1) and maintained at pH 7 in a growth media polluted with inorganic contaminants at levels expected based on the composition found in commercial coal flue gas systems. Contaminants present in the biomass and the medium at the end of a 7 day growth period were analytically quantified through cold vapor atomic absorption spectrometry for Hg and through inductively coupled plasma mass spectrometry for As, Cd, Co, Cr, Cu, Mn, Ni, Pb, Sb, Se, Sn, V and Zn. Results show N. salina is a sensitive strain to the multi-metal environment with a statistical decrease in biomass yieldwith the introduction of these contaminants. The techniques presented here are adequate for quantifying algal growth and determining the fate of inorganic contaminants. PMID- 26274062 TI - Practical Pd(II)-Catalyzed C-H Alkylation with Epoxides: One-Step Syntheses of 3,4-Dihydroisocoumarins. AB - Pd(II)-catalyzed ortho-alkylation of benzoic acids with both terminal and internal epoxides affords 3,4-dihydroisocoumarins in one step. The presence of potassium countercations is crucial for this reaction. Monoprotected amino acid ligands significantly promote this reaction, enabling the development of a practical C-H alkylation reaction using 0.5 mol % Pd catalyst. The inversion of stereochemistry in the C-H alkylation step is consistent with a redox-neutral SN2 nucleophilic ring-opening process as opposed to a Pd(II)/Pd(IV) pathway. PMID- 26274061 TI - Immigration, language proficiency, and autobiographical memories: Lifespan distribution and second-language access. AB - This investigation examined two controversies in the autobiographical literature: how cross-language immigration affects the distribution of autobiographical memories across the lifespan and under what circumstances language-dependent recall is observed. Both Spanish/English bilingual immigrants and English monolingual non-immigrants participated in a cue word study, with the bilingual sample taking part in a within-subject language manipulation. The expected bump in the number of memories from early life was observed for non-immigrants but not immigrants, who reported more memories for events surrounding immigration. Aspects of the methodology addressed possible reasons for past discrepant findings. Language-dependent recall was influenced by second-language proficiency. Results were interpreted as evidence that bilinguals with high second-language proficiency, in contrast to those with lower second-language proficiency, access a single conceptual store through either language. The final multi-level model predicting language-dependent recall, including second-language proficiency, age of immigration, internal language, and cue word language, explained 3/4 of the between-person variance and (1)/5 of the within-person variance. We arrive at two conclusions. First, major life transitions influence the distribution of memories. Second, concept representation across multiple languages follows a developmental model. In addition, the results underscore the importance of considering language experience in research involving memory reports. PMID- 26274063 TI - "Click" Patterning of Self-Assembled Monolayers on Hydrogen-Terminated Silicon Surfaces and Their Characterization Using Light-Addressable Potentiometric Sensors. AB - Two potential strategies for chemically patterning alkyne-terminated self assembled monolayers (SAMs) on oxide-free silicon or silicon-on-sapphire (SOS) substrates were investigated and compared. The patterned surfaces were validated using a light-addressable potentiometric sensor (LAPS) for the first time. The first strategy involved an integration of photolithography with "click" chemistry. Detailed surface characterization (i.e. water contact angle, ellipsometry, AFM, and XPS) and LAPS measurements showed that photoresist processing not only decreases the coverage of organic monolayers but also introduces chemically bonded contaminants on the surfaces, thus significantly reducing the quality of the SAMs and the utility of "click" surface modification. The formation of chemical contaminants in photolithography was also observed on carboxylic acid- and alkyl-terminated monolayers using LAPS. In contrast, a second approach combined microcontact printing (MUCP) with "click" chemistry; that is azide (azido-oligo(ethylene glycol) (OEG)-NH2) inks were printed on alkyne-terminated SAMs on silicon or SOS through PDMS stamps. The surface characterization results for the sample printed with a flat featureless PDMS stamp demonstrated a nondestructive and efficient method of MUCP to perform "click" reactions on alkyne-terminated, oxide-free silicon surfaces for the first time. For the sample printed with a featured PDMS stamp, LAPS imaging showed a good agreement with the pattern of the PDMS stamp, indicating the successful chemical patterning on non-oxidized silicon and SOS substrates and the capability of LAPS to image the molecular patterns with high sensitivity. PMID- 26274064 TI - Antiviral phytochemicals identification from Azadirachta indica leaves against HCV NS3 protease: an in silico approach. AB - Hepatitis C virus (HCV) is a major health problem across the world affecting the people of all age groups. It is the main cause of hepatitis and at chronic stage causes liver cirrhosis and hepatocellular carcinoma. Various therapeutics are made against HCV but still there is a need to find out potential therapeutics to combat the virus. The goal of this study is to identify the phytochemicals of Azadirachta indica leaves having antiviral activity against HCV NS3 protease through molecular docking and simulation approach. Results show that the compound 3-Deacetyl-3-cinnamoyl-azadirachtin possesses good binding properties with HCV NS3/4A protease. It can be concluded from this study that Deacetyl-3-cinnamoyl azadirachtin may serve as a potential inhibitor against NS3/4A protease. PMID- 26274065 TI - Risk factors associated with resistance to HIV testing among transwomen in Brazil. AB - Transwomen are a high-risk population for HIV/AIDS worldwide. However, many transwomen do not test for HIV. This study aimed to identify factors associated with resistance to HIV testing among transwomen in Fortaleza/CE. A cross sectional study was conducted between August and December 2008 with a sample of 304 transwomen recruited through respondent-driven sampling. Data analysis utilized Respondent-Driven Sampling Analysis Tool and SPSS 11.0. Univariate, bivariate, and multivariate analyses examined risk factors associated with resistance to HIV testing. Less than 18 years of age (OR = 4.221; CI = 2.419 7.364), sexual debut before 10 years of age (OR = 6.760; CI = 2.996-15.256), using illegal drugs during sex (OR = 2.384; CI = 1.310-4.339), experience of discrimination (OR = 3.962; CI = 1.540-10.195) and a belief that the test results were not confidential (OR = 3.763; CI = 2.118-6.688) are independently associated with resistance to testing. Intersectoral and targeted strategies aimed at encouraging the adoption of safer sexual behaviors and testing for HIV among transwomen are required. PMID- 26274066 TI - Direct MD Simulations of Terahertz Absorption and 2D Spectroscopy Applied to Explosive Crystals. AB - A direct molecular dynamics simulation of the THz spectrum of a molecular crystal is presented. A time-dependent electric field is added to a molecular dynamics simulation of a crystal slab. The absorption spectrum is composed from the energy dissipated calculated from a series of applied pulses characterized by a carrier frequency. The spectrum of crystalline cyclotrimethylenetrinitramine (RDX) and triacetone triperoxide (TATP) were simulated with the ReaxFF force field. The proposed direct method avoids the linear response and harmonic approximations. A multidimensional extension of the spectroscopy is suggested and simulated based on the nonlinear response to a single polarized pulse of radiation in the perpendicular polarization direction. PMID- 26274067 TI - Photochemical Charge Separation in Nanocrystal Photocatalyst Films: Insights from Surface Photovoltage Spectroscopy. AB - Photochemical charge generation, separation, and transport at nanocrystal interfaces are central to photoelectrochemical water splitting, a pathway to hydrogen from solar energy. Here, we use surface photovoltage spectroscopy to probe these processes in nanocrystal films of HCa2Nb3O10, a proven photocatalyst. Charge injection from the nanoparticles into the gold support can be observed, as well as oxidation and reduction of methanol and oxygen adsorbates on the nanosheet films. The measured photovoltage depends on the illumination intensity and substrate material, and it varies with illumination time and with film thickness. The proposed model predicts that the photovoltage is limited by the built-in potential of the nanosheet-metal junction, that is, the difference of Fermi energies in the two materials. The ability to measure and understand these light-induced charge separation processes in easy-to-fabricate films will promote the development of nanocrystal applications in photoelectrochemical cells, photovoltaics, and photocatalysts. PMID- 26274068 TI - Interface for Light-Driven Electron Transfer by Photosynthetic Complexes Across Block Copolymer Membranes. AB - Incorporation of membrane proteins into nanodevices to mediate recognition and transport in a collective and scalable fashion remains a challenging problem. We demonstrate how nanoscale photovoltaics could be designed using robust synthetic nanomembranes with incorporated photosynthetic reaction centers (RCs). Specifically, RCs from Rhodobacter sphaeroides are reconstituted spontaneously into rationally designed polybutadiene membranes to form hierarchically organized proteopolymer membrane arrays via a charge-interaction-directed reconstitution mechanism. Once incorporated, the RCs are fully active for prolonged periods based upon a variety of spectroscopic measurements, underscoring preservation of their 3D pigment configuration critical for light-driven charge transfer. This result provides a strategy to construct solar conversion devices using structurally versatile proteopolymer membranes with integrated RC functions to harvest broad regions of the solar spectrum. PMID- 26274069 TI - Elucidation and Control of an Intramolecular Charge Transfer Property of Fucoxanthin by a Modification of Its Polyene Chain Length. AB - Fucoxanthin is an essential pigment for the highly efficient light-harvesting function of marine algal photosynthesis. It exhibits excited state properties attributed to intramolecular charge transfer (ICT) in polar environments due to the presence of the carbonyl group in its polyene backbone. This report describes the excited state properties of fucoxanthin homologues with four to eight conjugated double bonds in various solvents using the femtosecond pump-probe technique. The results clarified that fucoxanthin homologues with longer polyene chains did not possess pronounced ICT spectroscopic signatures, while the shorter fucoxanthin homologues had a strong ICT character, even in a nonpolar solvent. On the basis of the observations, we quantitatively correlated the ICT character in the excited state to the conjugated polyene chain lengths of fucoxanthin molecules. PMID- 26274070 TI - Photoactive Dendrimer for Water Photoreduction: A Scaffold to Combine Sensitizers and Catalysts. AB - We report on the synthesis and characterization of platinum nanoparticles (PtNps) inside the cavities of a PAMAM dendrimer decorated with [Ru(bpy)3](2+) units at the periphery. The phosphorescent ruthenium complexes are used as signaling units of the Pt(2+) complexation in the dendritic architecture and as photosensitizer units in the photocatalytic production of H2 from water. This is the first example of water photoreduction in which the catalyst and the sensitizer are anchored on a dendritic molecular scaffold. This study provides a new outlook in the design of new supramolecular systems and materials for developing artificial photosynthesis. PMID- 26274071 TI - Developing Monolithic Nanoporous Gold with Hierarchical Bicontinuity Using Colloidal Bijels. AB - We report a universal platform for the synthesis of monolithic porous gold materials with hierarchical bicontinuous morphology and combined macro- and mesoporosity using a synergistic combination of nanocasting and chemical dealloying. This robust and accessible approach offers a new design paradigm for the parallel optimization of active surface area and mass transport in porous metal electrodes. PMID- 26274073 TI - Unveiling the Surface Structure of Amorphous Solid Water via Selective Infrared Irradiation of OH Stretching Modes. AB - In the quest to understand the formation of the building blocks of life, amorphous solid water (ASW) is one of the most widely studied molecular systems. Indeed, ASW is ubiquitous in the cold interstellar medium (ISM), where ASW-coated dust grains provide a catalytic surface for solid phase chemistry, and is believed to be present in the Earth's atmosphere at high altitudes. It has been shown that the ice surface adsorbs small molecules such as CO, N2, or CH4, most likely at OH groups dangling from the surface. Our study presents completely new insights concerning the behavior of ASW upon selective infrared (IR) irradiation of its dangling modes. When irradiated, these surface H2O molecules reorganize, predominantly forming a stabilized monomer-like water mode on the ice surface. We show that we systematically provoke "hole-burning" effects (or net loss of oscillators) at the wavelength of irradiation and reproduce the same absorbed water monomer on the ASW surface. Our study suggests that all dangling modes share one common channel of vibrational relaxation; the ice remains amorphous but with a reduced range of binding sites, and thus an altered catalytic capacity. PMID- 26274072 TI - Structure and Stability of Lithium Superoxide Clusters and Relevance to Li-O2 Batteries. AB - The discharge mechanism of a Li-O2 battery involves lithium superoxide (LiO2) radicals. In this Letter, we have performed high-level quantum chemical calculations (G4MP2) to investigate the structure and stability of LiO2 clusters. The clusters have planar ring-shaped structures, high spins, and are thermodynamically more stable than LiO2 dimer. The computed energy barrier for disproportionation of the larger clusters is also significantly higher than the corresponding barrier in the LiO2 dimer (1.0 eV vs 0.5 eV). This means that disproportionation rate should be much slower if the reaction involves LiO2 clusters other than the dimer. As a result, the clusters may survive long enough to be incorporated into the growing discharge product. These results are discussed in terms of recent experimental studies of the electronic structure and morphology of the discharge products in Li-air batteries. PMID- 26274074 TI - Efficiency of Solar-Light-Driven TiO2 Photocatalysis at Different Latitudes and Seasons. Where and When Does TiO2 Really Work? PMID- 26274075 TI - Role of Ordered Proteins in the Folding-Upon-Binding of Intrinsically Disordered Proteins. AB - In this work, we quantitatively investigate the thermodynamic analogy between the folding of monomeric proteins and the interactions of intrinsically disordered proteins (IDPs). Motivated by the hypothesis that similar hydrophobic forces guide both globular protein folding and also IDP interactions, we present a unified experimental and computational investigation of the coupling between the folding and binding of the intrinsically disordered tail of FCP1 when interacting with the cooperatively folding winged-helix domain of Rap74. Our calorimetric measurements quantitatively demonstrate the significance of hydrophobic interactions for this binding event. Our computational studies indicate that IDPs relieve frustration at the surface of ordered proteins to generate a minimally frustrated complex that is strikingly similar to a globular monomeric protein. In summary, these results not only quantify the thermodynamic forces driving disordered protein interactions but also highlight the role of ordered proteins for IDP function. PMID- 26274076 TI - Mapping the Ultrafast Dynamics of Adenine onto Its Nucleotide and Oligonucleotides by Time-Resolved Photoelectron Imaging. AB - The intrinsic photophysics of nucleobases and nucleotides following UV absorption presents a key reductionist step toward understanding the complex photodamage mechanisms occurring in DNA. The decay mechanism of adenine in particular has been the focus of intense investigation, as has how these correlate to those of its more biologically relevant nucleotide and oligonucleotides in aqueous solution. Here, we report on time-resolved photoelectron imaging of the deprotonated 3'-deoxy-adenosine-5'-monophosphate nucleotide and the adenosine di- and trinucleotides. Through a comparison of gas- and solution-phase experiments and available theoretical studies, the dynamics of the base are shown to be relatively insensitive to the surrounding environment. The decay mechanism primarily involves internal conversion from the initially populated (1)pipi* states to the ground state. The relaxation dynamics of the adenosine oligonucleotides are similar to those of the nucleobase, in contrast to the aqueous oligonucleotides, where a fraction of the ensemble forms long-lived excimer states. PMID- 26274077 TI - Hard Numbers for Large Molecules: Toward Exact Energetics for Supramolecular Systems. AB - Noncovalent interactions are ubiquitous in molecular and condensed-phase environments, and hence a reliable theoretical description of these fundamental interactions could pave the way toward a more complete understanding of the microscopic underpinnings for a diverse set of systems in chemistry and biology. In this work, we demonstrate that recent algorithmic advances coupled to the availability of large-scale computational resources make the stochastic quantum Monte Carlo approach to solving the Schrodinger equation an optimal contender for attaining "chemical accuracy" (1 kcal/mol) in the binding energies of supramolecular complexes of chemical relevance. To illustrate this point, we considered a select set of seven host-guest complexes, representing the spectrum of noncovalent interactions, including dispersion or van der Waals forces, pi-pi stacking, hydrogen bonding, hydrophobic interactions, and electrostatic (ion dipole) attraction. A detailed analysis of the interaction energies reveals that a complete theoretical description necessitates treatment of terms well beyond the standard London and Axilrod-Teller contributions to the van der Waals dispersion energy. PMID- 26274078 TI - Direct Electronic Property Imaging of a Nanocrystal-Based Photovoltaic Device by Electron Beam-Induced Current via Scanning Electron Microscopy. AB - Scanning electron microscopy (SEM) electron beam-induced current (EBIC) studies were performed on the cross-section of a nanocrystal-based hybrid bulk heterojunction photovoltaic device. Using these techniques, the short circuit carrier collection efficiencies are mapped with a better than 100 nm resolution. Electronically deficient and proficient regions within the photoactive layer are determined. The results show that only a fraction of the CdSe nanorod:P3HT layer (P3HT = poly-3(hexylthiophene)) at the Al cathode interface shows primary collection of charged carriers, in which the photoactivity decreases exponentially away from the interface. The recombination losses of the photoactive layer away from this interface prove that the limiting factor of the device is the inability for electrons to percolate between nanoparticles; to alleviate this problem, an interparticle network that conducts the electrons from one nanorod to the next must be established. Furthermore, the EBIC technique applied to the nanocrystalline device used in this study is the first measurement of its kind and can be applied toward other similar architectures. PMID- 26274079 TI - Understanding Trends in CO2 Adsorption in Metal-Organic Frameworks with Open Metal Sites. AB - Using van der Waals-corrected density functional theory and a local chemical bond analysis, we study and explain trends in the binding between CO2 and open-metal coordination sites within a series of two metal-organic frameworks (MOFs), BTT, and MOF-74 for Ca, Mg, and nine divalent transition-metal cations. We find that Ti and V result in the largest CO2 binding energies and show that for these cations the CO2 binding energies for both structure types are twice the value expected based on pure electrostatics. We associate this behavior with the specific electronic configuration of the divalent cations and symmetry of the metal coordination site upon CO2 binding, which result in empty antibonding orbitals between CO2 and the metal cation. We demonstrate that a chemical bond analysis and electrostatic considerations can be used to predict trends of CO2 binding affinities to MOFs with transition-metal cations. PMID- 26274080 TI - Time-Resolved Studies of the Acoustic Vibrational Modes of Metal and Semiconductor Nano-objects. AB - Over the past decade, there have been a number of transient absorption studies of the acoustic vibrational modes of metal and semiconductor nanoparticles. This Perspective provides an overview of this work. The way that the frequencies of the observed modes depend on the size and shape of the particles is described, along with their damping. Future research directions are also discussed, especially how these measurements provide information about the way nano-objects interact with their environment. PMID- 26274081 TI - Chemical Control of Hydrodynamic Instabilities in Partially Miscible Two-Layer Systems. AB - Hydrodynamic instabilities at the interface between two partially miscible liquids impact numerous applications, including CO2 sequestration in saline aquifers. We introduce here a new laboratory-scale model system on which buoyancy and Marangoni-driven convective instabilities of such partially miscible two layer systems can easily be studied. This system consists of the stratification of a pure alkyl formate on top of a denser aqueous solution in the gravitational field. A rich spectrum of convective dynamics is obtained upon partial dissolution of the ester into the water followed by its hydrolysis. The properties of the convective patterns are controlled by the miscibility of the ester in water, the feedback of the dissolved species on its own miscibility, as well as the reactivity of given chemicals in the aqueous solution with the solubilized ester. PMID- 26274082 TI - Key Parameters Governing the Energy Density of Rechargeable Li/S Batteries. AB - Rechargeable lithium-sulfur batteries have high theoretical capacity and energy density. However, their volumetric energy density has been believed to be lower than that of conventional lithium ion batteries employing metal oxide cathodes like LiCoO2. Here, we study the effects of sulfur loading percentage, develop a simple model and calculate the gravimetric and volumetric energy densities based on the total composition of electrodes in a lithium-sulfur cell, and compare those results with a typical graphite/LiCoO2 cell. From the model output, we have identified and established key parameters governing the energy density of rechargeable Li/S batteries. We find that the sulfur loading percentage has a much higher impact on the volumetric energy density than on the gravimetric energy density. A lithium-sulfur cell can exceed a lithium ion cell's volumetric energy density but only at high sulfur loading percentages (ca. 70%). We believe that these findings may attract more attention of lithium-sulfur system studies to high sulfur loading levels. PMID- 26274083 TI - A Mononuclear Mn(II) Pseudoclathrochelate Complex Studied by Multi-Frequency Electron-Paramagnetic-Resonance Spectroscopy. AB - Knowledge of the correlation between structural and spectroscopic properties of transition-metal complexes is essential to deepen the understanding of their role in catalysis, molecular magnetism, and biological inorganic chemistry. It provides topological and, sometimes, functional insight with respect to the active site properties of metalloproteins. The electronic structure of a high spin mononuclear Mn(II) pseudoclathrochelate complex has been investigated by electron-paramagnetic-resonance (EPR) spectroscopy at 9.5 and 275.7 GHz. A substantial, virtually axial zero-field splitting with D = -9.7 GHz (-0.32 cm( 1)) is found, which is the largest one reported to date for a Mn(II) complex with six nitrogen atoms in the first coordination sphere. PMID- 26274084 TI - Metastability Limit for the Nucleation of NaCl Crystals in Confinement. AB - We study the spontaneous nucleation and growth of sodium chloride crystals induced by controlled evaporation in confined geometries (microcapillaries) spanning several orders of magnitude in volume. In all experiments, the nucleation happens reproducibly at a very high supersaturation S ~ 1.6 and is independent of the size, shape, and surface properties of the microcapillary. We show from classical nucleation theory that this is expected: S ~ 1.6 corresponds to the point where nucleation first becomes observable on experimental time scales. A consequence of the high supersaturations reached at the onset of nucleation is the very rapid growth of a single skeletal (Hopper) crystal. Experiments on porous media also reveal the formation of Hopper crystals in the entrapped liquid pockets in the porous network and consequently underline the fact that sodium chloride can easily reach high supersaturations, in spite of what is commonly assumed for this salt. PMID- 26274085 TI - Overcoming the Myths of the Review Process and Getting Your Paper Ready for Publication. PMID- 26274086 TI - Mechanical Manipulation of Chemical Reactions: Reactivity Switching of Bergman Cyclizations. AB - Photoswitches incorporated into molecular frameworks have been used since a long time to trigger chemical processes on demand. Here, it is shown how mechanophores can be used as switches in order to drastically change the reactivity of a neighboring functional group as a function of external stress. The reactivities of cyclic enediynes, which are highly toxic agents when undergoing Bergman cyclization, roughly correlate with the distance between the bond-forming carbons in many cases. It is demonstrated how this distance, and thus enediyne reactivity, can be tuned upon applying mechanical stress. Depending on suitable substitution patterns, chemically inert species can be turned into highly reactive ones and vice versa, thus extending the concept of photoswitching to mechanoswitching. Moreover, depending on the derivative, it is found that C1-C5 cyclization becomes energetically preferred over the Bergman (C1-C6) pathway at nano-Newton forces, thus leading to a force-induced switch in selectivity in such cases. PMID- 26274087 TI - Temperature-Driven Changeover in the Electron-Transfer Mechanism of a Thermophilic Plastocyanin. AB - Electron-transfer kinetics of the thermophilic protein Plastocyanin from Phormidium laminosum adsorbed on 1,omega-alkanedithiol self-assembled monolayers (SAMs) deposited on gold have been investigated. The standard electron-transfer rate constant has been determined as a function of electrode-protein distance and solution viscosity over a broad temperature range (0-90 degrees C). For either thin or thick SAMs, the electron-transfer regime remains invariant with temperature, whereas for the 1,11-undecanethiol SAM of intermediate chain length, a kinetic regime changeover from a gated or friction-controlled mechanism at low temperature (0-30 degrees C) to a nonadiabatic mechanism above 40 degrees C is observed. To the best of our knowledge, this is the first time a thermal-induced transition between these two kinetic regimes is reported for a metalloprotein. PMID- 26274088 TI - The Use of Redox Mediators for Enhancing Utilization of Li2S Cathodes for Advanced Li-S Battery Systems. AB - The development of Li2S electrodes is a crucial step toward industrial manufacturing of Li-S batteries, a promising alternative to Li-ion batteries due to their projected two times higher specific capacity. However, the high voltages needed to activate Li2S electrodes, and the consequent electrolyte solution degradation, represent the main challenge. We present a novel concept that could make feasible the widespread application of Li2S electrodes for Li-S cell assembly. In this concept, the addition of redox mediators as additives to the standard electrolyte solution allows us to recover most of Li2S theoretical capacity in the activation cycle at potentials as low as 2.9 VLi, substantially lower than the typical potentials >4 VLi needed with standard electrolyte solution. Those novel additives permit us to preserve the electrolyte solution from being degraded, allowing us to achieve capacity as high as 500 mAhg(-1)Li2S after 150 cycles with no major structural optimization of the electrodes. PMID- 26274089 TI - Highly Sensitive Ammonia Probes of a Variable Proton-to-Electron Mass Ratio. AB - The mass sensitivity of the vibration-rotation-inversion energy levels of ammonia is probed using the nonrigid inverter theory. It is shown that the sensitivity exhibits non-negligible centrifugal distortion dependence, which is currently disregarded. The centrifugal distortion effects are especially important in the case of the Deltak = +/-3 "forbidden" transitions involving accidentally coinciding ro-inversional states |a,J,K = 3? and |s,J,K = 0? of the nu2 vibrational state of (14)NH3. The energy differences of these states exhibit very anomalous mass sensitivities (see Jansen etal. J. Chem. Phys. 2014 , 140 , 010901 ), thus appearing as new highly sensitive probes of the cosmological variability of the proton-to-electron mass ratio. PMID- 26274090 TI - Solvent Environment Revealed by Positively Chirped Pulses. AB - The spectroscopy of large organic molecules and biomolecules in solution has been investigated using various time-resolved and frequency-resolved techniques. Of particular interest is the early response of the molecule and the solvent, which is difficult to study due to the ambiguity in assigning and differentiating inter and intramolecular contributions to the electronic and vibrational populations and coherence. Our measurements compare the yield of fluorescence and stimulated emission for two laser dyes IR144 and IR125 as a function of chirp. While negatively chirped pulses are insensitive to solvent viscosity, positively chirped pulses are found to be uniquely sensitive probes of solvent viscosity. The fluorescence maximum for IR125 is observed near transform-limited pulses; however, for IR144, it is observed for positively chirped pulses once the pulses have been stretched to hundreds of femtoseconds. We conclude that chirped pulse spectroscopy is a simple one-beam method that is sensitive to early solvation dynamics. PMID- 26274091 TI - Formation of High-Aspect-Ratio Helical Nanorods via Chiral Self-Assembly of Fullerodendrimers. AB - Two novel, asymmetric methanofullerenes are presented, which self-assemble in cyclohexane upon thermal cycling to 80 degrees C. We show that, through the introduction of a dipeptide sequence to one terminus of the dendritic methanofullerene, it is possible to transform the assembly behavior of these molecules from poorly formed aggregates to high-aspect-ratio nanorods. These nanorods have diameters of 3.76 +/- 0.52 nm and appear to be composed of interwoven helices of dendritic fullerenes. As evidenced by circular dichroism, the helicity is characterized by a preferential handedness of assembly, which is imparted by the dipeptide moiety. PMID- 26274092 TI - Density Functional Theory Study Predicts Low Reorganization Energies for Azadipyrromethene-Based Metal Complexes. AB - Small internal reorganization energy is desirable for high-performance optoelectronic materials, as it facilitates both charge separation and charge transport. However, only a handful of n-type electron accepting materials are known to have small reorganization energies. Here, DFT calculations were performed to predict the reorganization energy of azadipyrromethene-based dyes and their complexes. All compounds studied were most stable in their anionic state and had high electron affinity, indicating their potential as n-type material. The homoleptic zinc(II) complexes had significantly lower reorganization energies than either the free ligands or the BF2(+) chelates. The low reorganization energies of the zinc(II) complexes are explained by the large and rigid pi conjugated system that extends across the two azadipyrromethene ligands via interligand pi-pi interactions. This work suggests that Zn(II) complexation is a novel strategy for obtaining materials that combine low internal reorganization energy with high electron affinity for the development of novel n-type optoelectronic materials. PMID- 26274093 TI - Broadband Transient Absorption and Two-Dimensional Electronic Spectroscopy of Methylene Blue. AB - Broadband transient absorption and two-dimensional electronic spectroscopy (2DES) studies of methylene blue in aqueous solution are reported. By isolating the coherent oscillations of the nonlinear signal amplitude and Fourier transforming with respect to the population time, we analyzed a significant number of coherences in the frequency domain and compared them with predictions of the vibronic spectrum from density function theory (DFT) calculations. We show here that such a comparison enables reliable assignments of vibrational coherences to particular vibrational modes, with their constituent combination bands and overtones also being identified via Franck-Condon analysis aided by DFT. Evaluation of the Fourier transform (FT) spectrum of transient absorption recorded to picosecond population times, in coincidence with 2D oscillation maps that disperse the FT spectrum into the additional excitation axis, is shown to be a complementary approach toward detailed coherence determination. Using the Franck-Condon overlap integrals determined from DFT calculations, we modeled 2D oscillation maps up to two vibrational quanta in the ground and excited state (six-level model), showing agreement with experiment. This semiquantitative analysis is used to interpret the geometry change upon photoexcitation as an expansion of the central sulfur/nitrogen containing ring due to the increased antibonding character in the excited state. PMID- 26274094 TI - Probing the biological evaluations of a new designed Pt(II) complex using spectroscopic and theoretical approaches: human hemoglobin as a target. AB - In recent years, using heavy metal compounds such as platinum as anticancer agent is one of the common ways in chemical therapy. In this study, a new anticancer compound of glycine derivatives of Pt(II) complex (amyl-glycine1, 10 phenanthroline Platinum nitrate) was designed, and the biological effects of this novel compound on the alterations in the function and structure of human hemoglobin (Hb) at different temperatures of 25 and 37 degrees C were assessed by applying various spectroscopic (fluorescence and circular dichroism (CD)) and theoretical methods. Fluorescence data indicated the strong ability of Pt(II) complex to quench the intrinsic fluorescence of Hb. The binding constant, number of binding sites, and thermodynamic parameters at two temperatures were calculated, and the results indicated the major possibility of occurring van der Waals force or hydrogen bond interactions in the Pt(II) complex-Hb interaction. For evaluating the alteration of secondary structure of Hb upon interaction with various concentrations of complex, far-UV CD spectra were used and it was observed that in high dose of complex, significant changes were occurred which is indicative of some side effects in overdosing of this complex. On the other hand, the molecular docking results illustrate that are well in agreement in obtaining data with spectroscopy. Above results suggested that using Pt(II) complex as an anticancer agent, model drug in high-dose usage might cause some disordering in structure and function of Hb as well as improve understanding of the side effects of newly designed metal anticancer drugs undergoing. PMID- 26274095 TI - Dual Gate Black Phosphorus Field Effect Transistors on Glass for NOR Logic and Organic Light Emitting Diode Switching. AB - We have fabricated dual gate field effect transistors (FETs) with 12 nm-thin black phosphorus (BP) channel on glass substrate, where our BP FETs have a patterned-gate architecture with 30 nm-thick Al2O3 dielectrics on top and bottom of a BP channel. Top gate dielectric has simultaneously been used as device encapsulation layer, controlling the threshold voltage of FETs as well when FETs mainly operate under bottom gate bias. Bottom, top, and dual gate-controlling mobilities were estimated to be 277, 92, and 213 cm(2)/V s, respectively. Maximum ON-current was measured to be ~5 MUA at a drain voltage of -0.1 V but to be as high as ~50 MUA at -1 V, while ON/OFF current ratio appeared to be 3.6 * 10(3) V. As a result, our dual gate BP FETs demonstrate organic light emitting diode (OLED) switching for green and blue OLEDs, also demonstrating NOR logic functions by separately using top- and bottom-input. PMID- 26274096 TI - Orchestration of Structural, Stereoelectronic, and Hydrogen-Bonding Effects in Stabilizing Triplexes from Engineered Chimeric Collagen Peptides (Pro(X)-Pro(Y) Gly)6 Incorporating 4(R/S)-Aminoproline. AB - Collagens are an important family of structural proteins found in the extracellular matrix with triple helix as the characteristic structural motif. The collagen triplex is made of three left-handed polyproline II (PPII) helices with each PPII strand consisting of repetitive units of the tripeptide motif X-Y Gly, where the amino acids X and Y are most commonly proline (Pro) and 4R hydroxyproline (Hyp), respectively. A C4-endo pucker at X-site and C4-exo pucker at Y-site have been proposed to be the key for formation of triplex, and the nature of pucker is dependent on both the electronegativity and stereochemistry of the substituent. The present manuscript describes a new class of collagen analogues-chimeric cationic collagens-wherein both X- and Y-sites in collagen triad are simultaneously substituted by a combination of 4(R/S) (OH/NH2/NH3(+)/NHCHO)-prolyl units and triplex stabilities measured at different pHs and in EG:H2O. Based on the results a model has been proposed with the premise that any factors which specifically favor the ring puckers of C4-endo at X-site and C4-exo at Y-site stabilize the PPII conformation and hence the derived triplexes. The pH-dependent triplex stability uniquely observed with ionizable 4 amino substituent on proline enables one to define the critical combination of factors C4-(exo/endo), intraresidue H-bonding, stereoelectronic (R/S) and n -> pi* interactions in dictating the triplex strength. The ionizable NH2 substituent at C4 in R/S configuration is thus a versatile probe for delineating the triplex stabilizing factors and the results have potential for designing of collagen analogues with customized properties for material and biological applications. PMID- 26274097 TI - Preoperative Radioactive Seed Localization for Nonpalpable Breast Lesions: Technique, Pitfalls, and Solutions. AB - Iodine 125 ((125)I) radioactive seed localization has emerged as a reliable and safe alternative to wire localization for guidance during the surgical resection of nonpalpable breast lesions. The breast imager has a responsibility to be familiar with the general principles of this evolving technique, including its advantages and disadvantages as well as the technical differences involved in placement of seeds versus traditional wire localization. Although placement of (125)I seeds is conceptually similar to wire placement, there are additional technical considerations and safety measures that need to be addressed and implemented when radioactive seeds are used. We draw from our experience with more than 1000 cases of radioactive seed localization since inception of our program in 2009 to provide illustrative examples of not only the proper technique of radioactive seed localization, but also mishaps that may occur during this procedure, along with practical suggestions to prevent these problems. We examine some of the difficulties that we have encountered during radioactive seed localization at our institution, including bone wax mimicking the seed, the inadvertent deployment of seeds, the need for multiple seeds or supplemental wires, problematic seed locations, and difficulty in surgical retrieval of the seed. Recognizing the potential pitfalls of radioactive seed localization and understanding the appropriate guidelines and precautions for the safe, secure handling and placement of radioactive seeds is essential for a successful radioactive seed localization program. PMID- 26274099 TI - Corrigendum. PMID- 26274100 TI - Numerical estimate of the Kardar-Parisi-Zhang universality class in (2+1) dimensions. AB - We study the restricted solid on solid model for surface growth in spatial dimension d=2 by means of a multisurface coding technique that allows one to produce a large number of samples in the stationary regime in a reasonable computational time. Thanks to (i) a careful finite-size scaling analysis of the critical exponents and (ii) the accurate estimate of the first three moments of the height fluctuations, we can quantify the wandering exponent with unprecedented precision: chi(d=2)=0.3869(4). This figure is incompatible with the long-standing conjecture due to Kim and Koesterlitz that hypothesized chi(d=2)=2/5. PMID- 26274101 TI - Dynamic message-passing approach for kinetic spin models with reversible dynamics. AB - A method to approximately close the dynamic cavity equations for synchronous reversible dynamics on a locally treelike topology is presented. The method builds on (a) a graph expansion to eliminate loops from the normalizations of each step in the dynamics and (b) an assumption that a set of auxilary probability distributions on histories of pairs of spins mainly have dependencies that are local in time. The closure is then effectuated by projecting these probability distributions on n-step Markov processes. The method is shown in detail on the level of ordinary Markov processes (n=1) and outlined for higher order approximations (n>1). Numerical validations of the technique are provided for the reconstruction of the transient and equilibrium dynamics of the kinetic Ising model on a random graph with arbitrary connectivity symmetry. PMID- 26274102 TI - Recursive percolation. AB - We introduce a simple lattice model in which percolation is constructed on top of critical percolation clusters, and find compelling numerical evidence that it can be repeated recursively any number n of generations. In two dimensions, we determine the percolation thresholds up to n=5. The corresponding critical clusters become more and more compact as n increases, and define universal scaling functions of the standard two-dimensional form and critical exponents that are distinct for any n. This family of exponents differs from previously known universality classes, and cannot be accommodated by existing analytical methods. We confirm that recursive percolation is well defined also in three dimensions. PMID- 26274103 TI - Anomalous self-diffusion in a freely evolving granular gas near the shearing instability. AB - The self-diffusion coefficient of a granular gas in the homogeneous cooling state is analyzed near the shearing instability. Using mode-coupling theory, it is shown that the coefficient diverges logarithmically as the instability is approached, due to the coupling of the diffusion process with the shear modes. The divergent behavior, which is peculiar in granular gases and disappears in the elastic limit, does not depend on any other transport coefficient. The theoretical prediction is confirmed by molecular dynamics simulation results for two-dimensional systems. PMID- 26274098 TI - Recent advances in biosynthetic modeling of nitric oxide reductases and insights gained from nuclear resonance vibrational and other spectroscopic studies. AB - This Forum Article focuses on recent advances in structural and spectroscopic studies of biosynthetic models of nitric oxide reductases (NORs). NORs are complex metalloenzymes found in the denitrification pathway of Earth's nitrogen cycle where they catalyze the proton-dependent two-electron reduction of nitric oxide (NO) to nitrous oxide (N2O). While much progress has been made in biochemical and biophysical studies of native NORs and their variants, a clear mechanistic understanding of this important metalloenzyme related to its function is still elusive. We report herein UV-vis and nuclear resonance vibrational spectroscopy (NRVS) studies of mononitrosylated intermediates of the NOR reaction of a biosynthetic model. The ability to selectively substitute metals at either heme or nonheme metal sites allows the introduction of independent (57)Fe probe atoms at either site, as well as allowing the preparation of analogues of stable reaction intermediates by replacing either metal with a redox inactive metal. Together with previous structural and spectroscopic results, we summarize insights gained from studying these biosynthetic models toward understanding structural features responsible for the NOR activity and its mechanism. The outlook on NOR modeling is also discussed, with an emphasis on the design of models capable of catalytic turnovers designed based on close mimics of the secondary coordination sphere of native NORs. PMID- 26274104 TI - Bernal random loose packing through freeze-thaw cycling. AB - We study the effect of freeze-thaw cycling on the packing fraction of equal spheres immersed in water. The water located between the grains experiences a dilatation during freezing and a contraction during melting. After several cycles, the packing fraction converges to a particular value eta(infinity)=0.595 independently of its initial value eta(0). This behavior is well reproduced by numerical simulations. Moreover, the numerical results allow one to analyze the packing structural configuration. With a Voronoi partition analysis, we show that the piles are fully random during the whole process and are characterized by two parameters: the average Voronoi volume MU(v) (related to the packing fraction eta) and the standard deviation sigma(v) of Voronoi volumes. The freeze-thaw driving modify the volume standard deviation sigma(v) to converge to a particular disordered state with a packing fraction corresponding to the random loose packing fraction eta(BRLP) obtained by Bernal during his pioneering experimental work. Therefore, freeze-thaw cycling is found to be a soft and spatially homogeneous driving method for disordered granular materials. PMID- 26274105 TI - Spontaneous energy-barrier formation in entropy-driven glassy dynamics. AB - The description of activated relaxation of glassy systems in the multidimensional configurational space is a long-standing open problem. We develop a phenomenological description of the out-of-equilibrium dynamics of a model with a rough potential energy landscape and we analyze it both numerically and analytically. The model provides an example of dynamics where typical relaxation channels go over finite-potential energy barriers despite the presence of less energy-demanding escaping paths in configurational space; we expect this phenomenon to be also relevant in the thermally activated regime of realistic models of glass-formers. In this case, we found that typical dynamical paths episodically reach an high-fixed-threshold energy, unexpectedly giving rise to a simple thermally activated aging phenomenology. In order to unveil this peculiar aging behavior, we introduce a novel description of the dynamics in terms of spontaneously emerging dynamical basins. PMID- 26274106 TI - Negative Gaussian curvature from induced metric changes. AB - We revisit the light or heat-induced changes in topography of initially flat sheets of a solid that elongate or contract along patterned in-plane director fields. For radial or azimuthal directors, negative Gaussian curvature is generated-so-called "anticones." We show that azimuthal material displacements are required for the distorted state to be stretch free and bend minimizing. The resultant shapes are smooth and asterlike and can become reentrant in the azimuthal coordinate for large deformations. We show that care is needed when considering elastomers rather than glasses, although the former offer huge deformations. PMID- 26274107 TI - Spontaneous ordering of magnetic particles in liquid crystals: From chains to biaxial lamellae. AB - Using Monte Carlo computer simulations we explore the self-assembly and ordering behavior of a hybrid, soft magnetic system consisting of small magnetic nanospheres in a liquid-crystalline (LC) matrix. Inspired by recent experiments with colloidal rod matrices, we focus on conditions where the sphere and rod diameters are comparable. Already in the absence of a magnetic field, the nematic ordering of the LC can stabilize the formation of magnetic chains along the nematic or smectic director, yielding a state with local (yet no macroscopic) magnetic order. The chains, in turn, increase the overall nematic order, reflecting the complex interplay of the structure formation of the two components. When increasing the sphere diameter, the spontaneous uniaxial ordering is replaced by biaxial lamellar morphologies characterized by alternating layers of rods and magnetic chains oriented perpendicular to the rod's director. These ordering scenarios at zero field suggest a complex response of the resulting hybrid to external stimuli, such as magnetic fields and shear forces. PMID- 26274108 TI - Signal focusing through active transport. AB - The accuracy of molecular signaling in biological cells and novel diagnostic devices is ultimately limited by the counting noise floor imposed by the thermal diffusion. Motivated by the fact that messenger RNA and vesicle-engulfed signaling molecules transiently bind to molecular motors and are actively transported in biological cells, we show here that the random active delivery of signaling particles to within a typical diffusion distance to the receptor generically reduces the correlation time of the counting noise. Considering a variety of signaling particle sizes from mRNA to vesicles and cell sizes from prokaryotic to eukaryotic cells, we show that the conditions for active focusing faster and more precise signaling-are indeed compatible with observations in living cells. Our results improve the understanding of molecular cellular signaling and novel diagnostic devices. PMID- 26274109 TI - Effect of disorder on the contact probability of elongated conformations of biopolymers. AB - Biopolymers are characterized by heterogeneous interactions, and usually perform their biological tasks forming contacts within domains of limited size. Combining polymer theory with a replica approach, we study the scaling properties of the probability of contact formation in random heteropolymers as a function of their linear distance. It is found that, close to or above the theta point, it is possible to define a contact probability which is typical (i.e., "self averaging") for different realizations of the heterogeneous interactions, and which displays an exponential cutoff, dependent on temperature and on the interaction range. In many cases this cutoff is comparable with the typical sizes of domains in biopolymers. While it is well known that disorder causes interesting effects at low temperature, the behavior elucidated in the present study is an example of a nontrivial effect at high temperature. PMID- 26274110 TI - Asymptotic wave propagation in excitable media. AB - Wave shape and velocity are important issues in reaction-diffusion systems, and are often the result of competition in media with heterogeneous conduction properties. Asymptotic wave front propagation at maximal conduction velocity has been previously reported in the context of anisotropic cardiac tissue, but it is unknown whether this is a universal property of excitable tissues where conduction velocity can be locally modulated by mechanisms other than anisotropy. Here, we investigate the impact of conduction heterogeneities and boundary effects on wave propagation in excitable media. Following a theoretical analysis, we find that wave-front cusps occur where local velocity is reduced and that asymptotic wave fronts propagate at the maximal translational conduction velocity. Simulations performed in different reaction-diffusion systems, including cardiac tissue, confirm our theoretical findings. We conclude that this property can be found in a wide range of reaction-diffusion systems with excitable dynamics and that asymptotic wave-front shapes can be predicted. PMID- 26274111 TI - Predicting chaotic time series with a partial model. AB - Methods for forecasting time series are a critical aspect of the understanding and control of complex networks. When the model of the network is unknown, nonparametric methods for prediction have been developed, based on concepts of attractor reconstruction pioneered by Takens and others. In this Rapid Communication we consider how to make use of a subset of the system equations, if they are known, to improve the predictive capability of forecasting methods. A counterintuitive implication of the results is that knowledge of the evolution equation of even one variable, if known, can improve forecasting of all variables. The method is illustrated on data from the Lorenz attractor and from a small network with chaotic dynamics. PMID- 26274112 TI - Practical synchronization on complex dynamical networks via optimal pinning control. AB - We consider practical synchronization on complex dynamical networks under linear feedback control designed by optimal control theory. The control goal is to minimize global synchronization error and control strength over a given finite time interval, and synchronization error at terminal time. By utilizing the Pontryagin's minimum principle, and based on a general complex dynamical network, we obtain an optimal system to achieve the control goal. The result is verified by performing some numerical simulations on Star networks, Watts-Strogatz networks, and Barabasi-Albert networks. Moreover, by combining optimal control and traditional pinning control, we propose an optimal pinning control strategy which depends on the network's topological structure. Obtained results show that optimal pinning control is very effective for synchronization control in real applications. PMID- 26274113 TI - Violent relaxation in two-dimensional flows with varying interaction range. AB - Understanding the relaxation of a system towards equilibrium is a long-standing problem in statistical mechanics. Here we address the role of long-range interactions in this process by considering a class of two-dimensional flows where the interaction between fluid particles varies with the distance as ~r(alpha-2) for alpha>0. We find that changing alpha with a prescribed initial state leads to different flow patterns: for small alpha, a coarsening process leads to the formation of a sharp interface between two regions of homogenized alpha-vorticity; for large alpha, the flow is attracted to a stable dipolar structure through a filamentation process. Assuming that the energy E and the enstrophy Z are injected at a typical scale smaller than the domain scale L, we argue that convergence towards the equilibrium state is expected when the parameter (2pi/L)(alpha)E/Z tends to one, while convergence towards a dipolar state occurs systematically when this parameter tends to zero. This suggests that weak long-range interacting systems are more prone to relax towards an equilibrium state than strong long-range interacting systems. PMID- 26274114 TI - Capillary solitons on a levitated medium. AB - A water cylinder deposited on a heated channel levitates on its own generated vapor film owing to the Leidenfrost effect. This experimental setup permits the study of the one-dimensional propagation of surface waves in a free-to-move liquid system. We report the observation of gravity-capillary waves under a dramatic reduction of gravity (up to a factor 30), leading to capillary waves at the centimeter scale. The generated nonlinear structures propagate without deformation and undergo mutual collisions and reflections at the boundaries of the domain. They are identified as Korteweg-de Vries solitons with negative amplitude and subsonic velocity. The typical width and amplitude-dependent velocities are in excellent agreement with theoretical predictions based on a generalized Korteweg-de Vries equation adapted to any substrate geometry. When multiple solitons are present, they interact and form a soliton turbulencelike spectrum. PMID- 26274115 TI - Concentration-dependent diffusion instability in reactive miscible fluids. AB - We report on chemoconvective pattern formation phenomena observed in a two-layer system of miscible fluids filling a vertical Hele-Shaw cell. We show both experimentally and theoretically that the concentration-dependent diffusion coupled with frontal acid-base neutralization can give rise to the formation of a local unstable zone low in density, resulting in a perfectly regular cell-type convective pattern. The described effect gives an example of yet another powerful mechanism which allows the reaction-diffusion processes to govern the flow of reacting fluids under gravity conditions. PMID- 26274116 TI - Deformation and shape of flexible, microscale helices in viscous flow. AB - We examine experimentally the deformation of flexible, microscale helical ribbons with nanoscale thickness subject to viscous flow in a microfluidic channel. Two aspects of flexible microhelices are quantified: the overall shape of the helix and the viscous frictional properties. The frictional coefficients determined by our experiments are consistent with calculated values in the context of resistive force theory. The deformation of helices by viscous flow is well described by nonlinear finite extensibility. Under distributed loading, the pitch distribution is nonuniform, and from this we identify both linear and nonlinear behavior along the contour length of a single helix. Moreover, flexible helices are found to display reversible global to local helical transitions at a high flow rate. PMID- 26274118 TI - Quantitative phase-field modeling of dendritic electrodeposition. AB - A thin-interface phase-field model of electrochemical interfaces is developed based on Marcus kinetics for concentrated solutions, and used to simulate dendrite growth during electrodeposition of metals. The model is derived in the grand electrochemical potential to permit the interface to be widened to reach experimental length and time scales, and electroneutrality is formulated to eliminate the Debye length. Quantitative agreement is achieved with zinc Faradaic reaction kinetics, fractal growth dimension, tip velocity, and radius of curvature. Reducing the exchange current density is found to suppress the growth of dendrites, and screening electrolytes by their exchange currents is suggested as a strategy for controlling dendrite growth in batteries. PMID- 26274117 TI - Role of the ionization potential in nonequilibrium metals driven to absorption saturation. AB - A composite metallic foil (Al/Mg/Al) has been exposed to intense sub-100 fs free electron laser (FEL) pulses and driven to ultrafast massive photoionization. The resulting nonequilibrium state of matter has been monitored through absorption spectroscopy across the L(2,3) edge of Mg as a function of the FEL fluence. The raw spectroscopic data indicate that at about 100J/cm(2) the main absorption channels of the sample, i.e., Mg (2p->free) and oxidized Al (valence->free), are almost saturated. The spectral behavior of the induced transparency has been interpreted with an analytical approach based on an effective ionization potential of the generated solid-density plasma. PMID- 26274119 TI - Irreversible processes without energy dissipation in an isolated Lipkin-Meshkov Glick model. AB - For a certain class of isolated quantum systems, we report the existence of irreversible processes in which the energy is not dissipated. After a closed cycle in which the initial energy distribution is fully recovered, the expectation value of a symmetry-breaking observable changes from a value differing from zero in the initial state to zero in the final state. This entails the unavoidable loss of a certain amount of information and constitutes a source of irreversibility. We show that the von Neumann entropy of time-averaged equilibrium states increases in the same magnitude as a consequence of the process. We support this result by means of numerical calculations in an experimentally feasible system, the Lipkin-Meshkov-Glick model. PMID- 26274120 TI - Langevin formulation of a subdiffusive continuous-time random walk in physical time. AB - Systems living in complex nonequilibrated environments often exhibit subdiffusion characterized by a sublinear power-law scaling of the mean square displacement. One of the most common models to describe such subdiffusive dynamics is the continuous-time random walk (CTRW). Stochastic trajectories of a CTRW can be described in terms of the subordination of a normal diffusive process by an inverse Levy-stable process. Here, we propose an equivalent Langevin formulation of a force-free CTRW without subordination. By introducing a different type of non-Gaussian noise, we are able to express the CTRW dynamics in terms of a single Langevin equation in physical time with additive noise. We derive the full multipoint statistics of this noise and compare it with the scaled Brownian motion (SBM), an alternative stochastic model describing subdiffusive dynamics. Interestingly, these two noises are identical up to the second order correlation functions, but different in the higher order statistics. We extend our formalism to general waiting time distributions and force fields and compare our results with those of the SBM. In the presence of external forces, our proposed noise generates a different class of stochastic processes, resembling a CTRW but with forces acting at all times. PMID- 26274121 TI - Generalization of the Ehrenfest urn model to a complex network. AB - The Ehrenfest urn model is extended to a complex directed network, over which a conserved quantity is transported in a random fashion. The evolution of the conserved number of packets in each urn, or node of the network, is illustrated by means of a stochastic simulation. Using mean-field theory we were able to compute an approximation to the ensemble-average evolution of the number of packets in each node which, in the thermodynamic limit, agrees quite well with the results of the stochastic simulation. Using this analytic approximation we are able to find the asymptotic dynamical state of the system and the time scale to approach the equilibrium state, for different networks. The study is extended to large scale-free and small-world networks, in which the relevance of the connectivity distribution and the topology of the network for the distribution of time scales of the system is apparent. This analysis may contribute to the understanding of the transport properties in real networks subject to a perturbation, e.g., the asymptotic state and the time scale required to approach it. PMID- 26274122 TI - Statistics of work distribution in periodically driven closed quantum systems. AB - We study the statistics of the work distribution P(w) in a d-dimensional closed quantum system with linear dimension L subjected to a periodic drive with frequency omega(0). We show that the corresponding rate function I(w)= ln[P(w)/Lambda(0)]/L^{d} after a drive period satisfies a universal lower bound I(0)>=n(d) and has a zero at w=QL(d)/N, where n(d) and Q are the excitation and the residual energy densities generated during the drive, Lambda(0) is a constant fixed by the normalization of P(w), and N is the total number of constituent particles or spins in the system. We supplement our results by calculating I(w) for a class of d-dimensional integrable models and show that I(w) has an oscillatory dependence on omega(0) originating from Stuckelberg interference generated due to double passage through the critical point or region during the drive. We suggest experiments to test our theory. PMID- 26274123 TI - Langevin dynamics neglecting detailed balance condition. AB - An improved method for driving a system into a desired distribution, for example, the Gibbs-Boltzmann distribution, is proposed, which makes use of an artificial relaxation process. The standard techniques for achieving the Gibbs-Boltzmann distribution involve numerical simulations under the detailed balance condition. In contrast, in the present study we formulate the Langevin dynamics, for which the corresponding Fokker-Planck operator includes an asymmetric component violating the detailed balance condition. This leads to shifts in the eigenvalues and results in the acceleration of the relaxation toward the steady state. The numerical implementation demonstrates faster convergence and shorter correlation time, and the technique of biased event sampling, Nemoto-Sasa theory, further highlights the efficacy of our method. PMID- 26274124 TI - Kernel method for corrections to scaling. AB - Scaling analysis, in which one infers scaling exponents and a scaling function in a scaling law from given data, is a powerful tool for determining universal properties of critical phenomena in many fields of science. However, there are corrections to scaling in many cases, and then the inference problem becomes ill posed by an uncontrollable irrelevant scaling variable. We propose a new kernel method based on Gaussian process regression to fix this problem generally. We test the performance of the new kernel method for some example cases. In all cases, when the precision of the example data increases, inference results of the new kernel method correctly converge. Because there is no limitation in the new kernel method for the scaling function even with corrections to scaling, unlike in the conventional method, the new kernel method can be widely applied to real data in critical phenomena. PMID- 26274125 TI - Entropy production in a non-Markovian environment. AB - Stochastic thermodynamics and the associated fluctuation relations provide the means to extend the fundamental laws of thermodynamics to small scales and systems out of equilibrium. The fluctuating thermodynamic variables are usually treated in the context of either isolated Hamiltonian evolution, or Markovian dynamics in open systems. However, there is no reason a priori why the Markovian approximation should be valid in driven systems under nonequilibrium conditions. In this work, we introduce an explicitly non-Markovian model of dynamics of an open system, where the correlations between the system and the environment drive a subset of the environment out of equilibrium. Such an environment gives rise to a new type of non-Markovian entropy production term. Such non-Markovian components must be taken into account in order to recover the fluctuation relations for entropy. As a concrete example, we explicitly derive such modified fluctuation relations for the case of an overheated single electron box. PMID- 26274127 TI - A+A->? model with a bias towards nearest neighbor. AB - We have studied the A+A->? reaction-diffusion model on a ring, with a bias epsilon(0<=epsilon<=0.5) of the random walkers A to hop towards their nearest neighbor. Though the bias is local in space and time, we show that it alters the universality class of the problem. The z exponent, which describes the growth of average spacings between the walkers with time, changes from the value 2 at epsilon=0 to the mean-field value of unity for any nonzero epsilon. We study the problem analytically using independent interval approximation and compare the scaling results with those obtained from simulation. The distribution P(k,t) (per site) of the spacing between two walkers is given by t(-2/z)f(k/t(1/z)) and is obtained both analytically and numerically. We also obtain the result that epsilont becomes the new time scale for epsilon?0. PMID- 26274126 TI - Nonlocal response functions for predicting shear flow of strongly inhomogeneous fluids. II. Sinusoidally driven shear and multisinusoidal inhomogeneity. AB - We use molecular-dynamics computer simulations to investigate the density, strain rate, and shear-pressure responses of a simple model atomic fluid to transverse and longitudinal external forces. We have previously introduced a response function formalism for describing the density, strain-rate, and shear-pressure profiles in an atomic fluid when it is perturbed by a combination of longitudinal and transverse external forces that are independent of time and have a simple sinusoidal spatial variation. In this paper, we extend the application of the previously introduced formalism to consider the case of a longitudinal force composed of multiple sinusoidal components in combination with a single-component sinusoidal transverse force. We find that additional harmonics are excited in the density, strain-rate, and shear-pressure profiles due to couplings between the force components. By analyzing the density, strain-rate, and shear-pressure profiles in Fourier space, we are able to evaluate the Fourier coefficients of the response functions, which now have additional components describing the coupling relationships. Having evaluated the Fourier coefficients of the response functions, we are then able to accurately predict the density, velocity, and shear-pressure profiles for fluids that are under the influence of a longitudinal force composed of two or three sinusoidal components combined with a single component sinusoidal transverse force. We also find that in the case of a multisinusoidal longitudinal force, it is sufficient to include only pairwise couplings between different longitudinal force components. This means that it is unnecessary to include couplings between three or more force components in the case of a longitudinal force composed of many Fourier components, and this paves the way for a highly accurate but tractable treatment of nonlocal transport phenomena in fluids with density and strain-rate inhomogeneities on the molecular length scale. PMID- 26274128 TI - Quantum statistics and the performance of engine cycles. AB - We study the role of quantum statistics in the performance of Otto cycles. First, we show analytically that the work distributions for bosonic and fermionic working fluids are identical for cycles driven by harmonic trapping potentials. Subsequently, in the case of nonharmonic potentials, we find that the interplay between different energy level spacings and particle statistics strongly affects the performances of the engine cycle. To demonstrate this, we examine three trapping potentials which induce different (single-particle) energy level spacings: monotonically decreasing with the level number, monotonically increasing, and the case in which the level spacing does not vary monotonically. PMID- 26274129 TI - Polymers undergoing inhomogeneous adsorption: Order parameters for a partially directed walk model. AB - We consider partially directed walk models of polymers undergoing inhomogeneous adsorption. The inhomogeneity can be in the polymer, in the surface, or in both. For the cases where the polymer is either a homopolymer or a strictly alternating copolymer and where the surface is either homogeneous or has stripes of width 1, we calculate detailed order parameters and show that these provide important information about the ways in which the polymer adsorbs. PMID- 26274130 TI - Class of perfect 1/f noise and the low-frequency cutoff paradox. AB - The low-frequency cutoff paradox occurring in 1/f processes has been revisited in a recent Letter [M. Niemann, H. Kantz, and E. Barkai, Phys. Rev. Lett. 110, 140603 (2013)]. A model of independent pulses exhibiting an integrable 1/f(beta) power spectrum with beta>1 explains this paradox. In this paper we explore a complementary possibility based on the use of multiplicative models to generate integrable 1/f(beta) processes. Three distinct types of models are considered. One of the most used methods of generating 1/f processes based on correlated pulses is among these models. Consequently we find that, contrary to what is generally thought, the low-frequency cutoff is not necessary to avoid the postulated divergence in a wide variety of processes. PMID- 26274131 TI - Scaling behavior and complexity of plastic deformation for a bulk metallic glass at cryogenic temperatures. AB - We explore the scaling behavior and complexity in the shear-branching process during the compressive deformation of a bulk metallic glass Zr(64.13)Cu(15.75)Al(10)Ni(10.12) (at. %) at cryogenic temperatures. The fractal dimension of the stress rate signal ranges from 1.22 to 1.72 with decreasing temperature and a larger shear-branching rate occurs at lower temperature. A stochastic model is introduced for the shear-branching process. In particular, at a temperature of 213K, the shear-branching process evolves as a self-similar random process. In addition, the complexity of the stress rate signal conforms to the larger activation energy of the shear transformation zone at lower temperatures. PMID- 26274132 TI - Pseudochemotactic drifts of artificial microswimmers. AB - We numerically investigate the motion of active artificial microswimmers diffusing in a fuel concentration gradient. We observe that, in the steady state, their probability density accumulates in the low-concentration regions, whereas a tagged swimmer drifts with velocity depending in modulus and orientation on how the concentration gradient affects the self-propulsion mechanism. Under most experimentally accessible conditions, the particle drifts toward the high concentration regions (pseudochemotactic drift). A correct interpretation of experimental data must account for such an "anti-Fickian" behavior. PMID- 26274133 TI - Energy and magnetization transport in nonequilibrium macrospin systems. AB - We investigate numerically the magnetization dynamics of an array of nanodisks interacting through the magnetodipolar coupling. In the presence of a temperature gradient, the chain reaches a nonequilibrium steady state where energy and magnetization currents propagate. This effect can be described as the flow of energy and particle currents in an off-equilibrium discrete nonlinear Schrodinger (DNLS) equation. This model makes transparent the transport properties of the system and allows for a precise definition of temperature and chemical potential for a precessing spin. The present study proposes a setup for the spin-Seebeck effect, and shows that its qualitative features can be captured by a general oscillator-chain model. PMID- 26274134 TI - Scaling of the dynamics of a homogeneous one-dimensional anisotropic classical Heisenberg model with long-range interactions. AB - The dynamics of quasistationary states of long-range interacting systems with N particles can be described by kinetic equations such as the Balescu-Lenard and Landau equations. In the case of one-dimensional homogeneous systems, two-body contributions vanish as two-body collisions in one dimension only exchange momentum and thus cannot change the one-particle distribution. Using a Kac factor in the interparticle potential implies a scaling of the dynamics proportional to N(delta) with delta=1 except for one-dimensional homogeneous systems. For the latter different values for delta were reported for a few models. Recently it was shown by Rocha Filho and collaborators [Phys. Rev. E 90, 032133 (2014)] for the Hamiltonian mean-field model that delta=2 provided that N is sufficiently large, while small N effects lead to delta~1.7. More recently, Gupta and Mukamel [J. Stat. Mech. (2011) P03015] introduced a classical spin model with an anisotropic interaction with a scaling in the dynamics proportional to N(1.7) for a homogeneous state. We show here that this model reduces to a one-dimensional Hamiltonian system and that the scaling of the dynamics approaches N(2) with increasing N. We also explain from theoretical consideration why usual kinetic theory fails for small N values, which ultimately is the origin of noninteger exponents in the scaling. PMID- 26274135 TI - Construction and optimization of a quantum analog of the Carnot cycle. AB - The quantum analog of Carnot cycles in few-particle systems consists of two quantum adiabatic steps and two isothermal steps. This construction is formally justified by use of a minimum work principle. It is then shown, using minimal assumptions of work or heat in nanoscale systems, that the heat-to-work efficiency of such quantum heat engine cycles can be further optimized via two conditions regarding the expectation value of some generalized force operators evaluated at equilibrium states. In general the optimized efficiency is system specific, lower than the Carnot efficiency, and dependent upon both temperatures of the cold and hot reservoirs. Simple computational examples are used to illustrate our theory. The results should be an important guide towards the design of favorable working conditions of a realistic quantum heat engine. PMID- 26274136 TI - Critical and near-critical phase behavior and interplay between the thermodynamic Casimir and van der Waals forces in a confined nonpolar fluid medium with competing surface and substrate potentials. AB - We study, using general scaling arguments and mean-field type calculations, the behavior of the critical Casimir force and its interplay with the van der Waals force acting between two parallel slabs separated at a distance L from each other, confining some fluctuating fluid medium, say a nonpolar one-component fluid or a binary liquid mixture. The surfaces of the slabs are coated by thin layers exerting strong preference to the liquid phase of the fluid, or one of the components of the mixture, modeled by strong adsorbing local surface potentials ensuring the so-called (+,+) boundary conditions. The slabs, on the other hand, influence the fluid by long-range competing dispersion potentials, which represent irrelevant interactions in renormalization-group sense. Under such conditions, one usually expects attractive Casimir force governed by universal scaling function, pertinent to the extraordinary surface universality class of Ising type systems, to which the dispersion potentials provide only corrections to scaling. We demonstrate, however, that below a given threshold thickness of the system L(crit) for a suitable set of slabs-fluid and fluid-fluid coupling parameters the competition between the effects due to the coatings and the slabs can result in sign change of the Casimir force acting between the surfaces confining the fluid when one changes the temperature T, the chemical potential of the fluid MU, or L. The last implies that by choosing specific materials for the slabs, coatings, and the fluid for L?L(crit) one can realize repulsive Casimir force with nonuniversal behavior which, upon increasing L, gradually turns into an attractive one described by a universal scaling function, depending only on the relevant scaling fields related to the temperature and the excess chemical potential, for L?L(crit). We present arguments and relevant data for specific substances in support of the experimental feasibility of the predicted behavior of the force. It can be of interest, e.g., for designing nanodevices and for governing behavior of objects, say colloidal particles, at small distances. We formulate the corresponding criterion for determination of L(crit). The universality is regained for L?L(crit). We also show that for systems with L?L(crit), the capillary condensation phase diagram suffers modifications which one does not observe in systems with purely short-ranged interactions. PMID- 26274137 TI - Approximate probability distributions of the master equation. AB - Master equations are common descriptions of mesoscopic systems. Analytical solutions to these equations can rarely be obtained. We here derive an analytical approximation of the time-dependent probability distribution of the master equation using orthogonal polynomials. The solution is given in two alternative formulations: a series with continuous and a series with discrete support, both of which can be systematically truncated. While both approximations satisfy the system size expansion of the master equation, the continuous distribution approximations become increasingly negative and tend to oscillations with increasing truncation order. In contrast, the discrete approximations rapidly converge to the underlying non-Gaussian distributions. The theory is shown to lead to particularly simple analytical expressions for the probability distributions of molecule numbers in metabolic reactions and gene expression systems. PMID- 26274138 TI - Spectral density of generalized Wishart matrices and free multiplicative convolution. AB - We investigate the level density for several ensembles of positive random matrices of a Wishart-like structure, W=XX(?), where X stands for a non-Hermitian random matrix. In particular, making use of the Cauchy transform, we study the free multiplicative powers of the Marchenko-Pastur (MP) distribution, MP(?s), which for an integer s yield Fuss-Catalan distributions corresponding to a product of s-independent square random matrices, X=X(1)?X(s). New formulas for the level densities are derived for s=3 and s=1/3. Moreover, the level density corresponding to the generalized Bures distribution, given by the free convolution of arcsine and MP distributions, is obtained. We also explain the reason of such a curious convolution. The technique proposed here allows for the derivation of the level densities for several other cases. PMID- 26274139 TI - Susceptibilities for the Muller-Hartmann-Zitartz countable infinity of phase transitions on a Cayley tree. AB - We obtain explicit susceptibilities for the countable infinity of phase transition temperatures of Muller-Hartmann-Zitartz on a Cayley tree. The susceptibilities are a product of the zeroth spin with the sum of an appropriate set of averages of spins on the outermost layer of the tree. A clear physical understanding for these strange phase transitions emerges naturally. In the thermodynamic limit, the susceptibilities tend to zero above the transition and to infinity below it. PMID- 26274140 TI - Nonlocal quartic interactions and universality classes in perovskite manganites. AB - A modified Ginzburg-Landau model with a screened nonlocal interaction in the quartic term is treated via Wilson's renormalization-group scheme at one-loop order to explore the critical behavior of the paramagnetic-to-ferromagnetic phase transition in perovskite manganites. We find the Fisher exponent eta to be O(epsilon) and the correlation exponent to be nu=1/2+O(epsilon) through epsilon expansion in the parameter epsilon=d(c)-d, where d is the space dimension, d(c)=4+2sigma is the upper critical dimension, and sigma is a parameter coming from the nonlocal interaction in the model Hamiltonian. The ensuing critical exponents in three dimensions for different values of sigma compare well with various existing experimental estimates for perovskite manganites with various doping levels. This suggests that the nonlocal model Hamiltonian contains a wide variety of such universality classes. PMID- 26274141 TI - Thermophysical properties of supercritical water and bond flexibility. AB - Molecular dynamics results are reported for the thermodynamic properties of supercritical water using examples of both rigid (TIP4P/2005) and flexible (TIP4P/2005f) transferable interaction potentials. Data are reported for pressure, isochoric and isobaric heat capacities, the thermal expansion coefficient, isothermal and adiabatic compressibilities, Joule-Thomson coefficient, speed of sound, self-diffusion coefficient, viscosities, and thermal conductivity. Many of these properties have unusual behavior in the supercritical phase such as maximum and minimum values. The effectiveness of bond flexibility on predicting these properties is determined by comparing the results to experimental data. The influence of the intermolecular potential on these properties is both variable and state point dependent. In the vicinity of the critical density, the rigid and flexible potentials yield very different values for the compressibilities, heat capacities, and thermal expansion coefficient, whereas the self-diffusion coefficient, viscosities, and thermal conductivities are much less potential dependent. Although the introduction of bond flexibility is a computationally expedient way to improve the accuracy of an intermolecular potential, it can be counterproductive in some cases and it is not an adequate replacement for incorporating the effects of polarization. PMID- 26274142 TI - Levy flights and nonhomogenous memory effects: Relaxation to a stationary state. AB - The non-Markovian stochastic dynamics involving Levy flights and a potential in the form of a harmonic and nonlinear oscillator is discussed. The subordination technique is applied and the memory effects, which are nonhomogeneous, are taken into account by a position-dependent subordinator. In the nonlinear case, the asymptotic stationary states are found. The relaxation pattern to the stationary state is derived for the quadratic potential: the density decays like a linear combination of the Mittag-Leffler functions. It is demonstrated that in the latter case the density distribution satisfies a fractional Fokker-Planck equation. The densities for the nonlinear oscillator reveal a complex picture, qualitatively dependent on the potential strength, and the relaxation pattern is exponential at large time. PMID- 26274143 TI - Continuum percolation of polydisperse hyperspheres in infinite dimensions. AB - We analyze the critical connectivity of systems of penetrable d-dimensional spheres having size distributions in terms of weighed random geometrical graphs, in which vertex coordinates correspond to random positions of the sphere centers, and edges are formed between any two overlapping spheres. Edge weights naturally arise from the different radii of two overlapping spheres. For the case in which the spheres have bounded size distributions, we show that clusters of connected spheres are treelike for d->infinity and they contain no closed loops. In this case, we find that the mean cluster size diverges at the percolation threshold density eta(c)->2(-d), independently of the particular size distribution. We also show that the mean number of overlaps for a particle at criticality z(c) is smaller than unity, while z(c)->1 only for spheres with fixed radii. We explain these features by showing that in the large dimensionality limit, the critical connectivity is dominated by the spheres with the largest size. Assuming that closed loops can be neglected also for unbounded radii distributions, we find that the asymptotic critical threshold for systems of spheres with radii following a log-normal distribution is no longer universal, and that it can be smaller than 2(-d) for d->infinity. PMID- 26274144 TI - Stochastic thermodynamics for linear kinetic equations. AB - Stochastic thermodynamics is formulated for variables that are odd under time reversal. The invariance under spatial rotation of the collision rates due to the isotropy of the heat bath is shown to be a crucial ingredient. An alternative detailed fluctuation theorem is derived, expressed solely in terms of forward statistics. It is illustrated for a linear kinetic equation with kangaroo rates. PMID- 26274145 TI - Slowest local operators in quantum spin chains. AB - We numerically construct slowly relaxing local operators in a nonintegrable spin 1/2 chain. Restricting the support of the operator to M consecutive spins along the chain, we exhaustively search for the operator that minimizes the Frobenius norm of the commutator with the Hamiltonian. We first show that the Frobenius norm bounds the time scale of relaxation of the operator at high temperatures. We find operators with significantly slower relaxation than the slowest simple "hydrodynamic" mode due to energy diffusion. Then we examine some properties of the nontrivial slow operators. Using both exhaustive search and tensor network techniques, we find similar slowly relaxing operators for a Floquet spin chain; this system is hydrodynamically "trivial," with no conservation laws restricting their dynamics. We argue that such slow relaxation may be a generic feature following from locality and unitarity. PMID- 26274146 TI - Site trimer percolation on square lattices. AB - Percolation of site trimers (k-mers with k=3) is investigated in a detailed way making use of an analytical model based on renormalization techniques in this problem. Results are compared to those obtained here by means of extensive computer simulations. Five different deposition possibilities for site trimers are included according to shape and orientation of the depositing objects. Analytical results for the percolation threshold p(c) are all close to 0.55, while numerical results show a slight dispersion around this value. A comparison with p(c) values previously reported for monomers and dimers establishes the tendency of p(c) to decrease as k increases. Critical exponent nu was also obtained both by analytical and numerical methods. Results for the latter give values very close to the expected value 4/3 showing that this percolation case corresponds to the universality class of random percolation. PMID- 26274147 TI - Slow approach to steady motion of a concave body in a free-molecular gas. AB - A body in a free-molecular gas accelerated by a constant external force is considered on the basis of kinetic theory. The body is an infinitely long rectangular hollow column with one face removed, and thus it has a squarish U shaped cross section. The concave part of the body points toward the direction of motion, and thus the gas molecules may be trapped in the concavity. Gas molecules undergo diffuse reflection on a base part, whereas specular reflection on two lateral parts. It is numerically shown that the velocity of the body approaches a terminal velocity, for which a drag force exerted by the gas counterbalances the external force, in such a way that their difference decreases in proportion to the inverse square of time for a large time. This rate of approach is slower than the known rate proportional to the inverse cube of time in the case of a body without concavity [Aoki et al., Phys. Rev. E 80, 016309 (2009)]. Based on the detailed investigation on the velocity distribution function of gas molecules impinging on the body, it is clarified that the concavity prevents some molecules from escaping to infinity. This trapping enhances the effect of recollision between the body and the gas molecules, which is the cause of the inverse power laws, and thus leads to the slower approach. PMID- 26274148 TI - Jarzynski equality, Crooks fluctuation theorem, and the fluctuation theorems of heat for arbitrary initial states. AB - By taking full advantage of the dynamic property imposed by the detailed balance condition, we derive a new refined unified fluctuation theorem (FT) for general stochastic thermodynamic systems. This FT involves the joint probability distribution functions of the final phase-space point and a thermodynamic variable. Jarzynski equality, Crooks fluctuation theorem, and the FTs of heat as well as the trajectory entropy production can be regarded as special cases of this refined unified FT, and all of them are generalized to arbitrary initial distributions. We also find that the refined unified FT can easily reproduce the FTs for processes with the feedback control, due to its unconventional structure that separates the thermodynamic variable from the choices of initial distributions. Our result is heuristic for further understanding of the relations and distinctions between all kinds of FTs and might be valuable for studying thermodynamic processes with information exchange. PMID- 26274149 TI - Equivalence of matrix product ensembles of trajectories in open quantum systems. AB - The equivalence of thermodynamic ensembles is at the heart of statistical mechanics and central to our understanding of equilibrium states of matter. Recently, a formal connection has been established between the dynamics of open quantum systems and statistical mechanics in an extra dimension: an open system dynamics generates a matrix product state (MPS) encoding all possible quantum jump trajectories which allows to construct generating functions akin to partition functions. For dynamics generated by a Lindblad master equation, the corresponding MPS is a so-called continuous MPS which encodes the set of continuous measurement records terminated at some fixed total observation time. Here, we show that if one instead terminates trajectories after a fixed total number of quantum jumps, e.g., emission events into the environment, the associated MPS is discrete. The continuous and discrete MPS correspond to different ensembles of quantum trajectories, one characterized by total time, the other by total number of quantum jumps. Hence, they give rise to quantum versions of different thermodynamic ensembles, akin to "grand canonical" and "isobaric," but for trajectories. Here, we prove that these trajectory ensembles are equivalent in a suitable limit of long time or large number of jumps. This is in direct analogy to equilibrium statistical mechanics where equivalence between ensembles is only strictly established in the thermodynamic limit. An intrinsic quantum feature is that the equivalence holds only for all observables that commute with the number of quantum jumps. PMID- 26274150 TI - Two-phase coexistence for hydrogen-helium mixtures. AB - We use our quantum Gibbs ensemble Monte Carlo algorithm to perform computer experiments for the two-phase coexistence of a hydrogen-helium mixture. Our results are in quantitative agreement with the experimental results of Sneed, Streett, Sonntag, and Van Wylen. The difference between our results and the experimental ones is in all cases less than 15% relative to the experiment, reducing to less than 5% in the low helium concentration phase. At the gravitational inversion between the vapor and the liquid phase, at low temperatures and high pressures, the quantum effects become relevant. At extremely low temperature and pressure, the first component to show superfluidity is the helium in the vapor phase. PMID- 26274151 TI - Exploring different regimes in finite-size scaling of the droplet condensation evaporation transition. AB - We present a finite-size scaling analysis of the droplet condensation-evaporation transition of a lattice gas (in two and three dimensions) and a Lennard-Jones gas (in three dimensions) at fixed density. Parallel multicanonical simulations allow sampling of the required system sizes with precise equilibrium estimates. In the limit of large systems, we verify the theoretical leading-order scaling prediction for both the transition temperature and the finite-size rounding. In addition, we present an emerging intermediate scaling regime, consistent in all considered cases and with similar recent observations for polymer aggregation. While the intermediate regime locally may show a different effective scaling, we show that it is a gradual crossover to the large-system scaling behavior by including empirical higher-order corrections. This implies that care has to be taken when considering scaling ranges, possibly leading to completely wrong predictions for the thermodynamic limit. In this study, we consider a crossing of the phase boundary orthogonal to the usual fixed temperature studies. We show that this is an equivalent approach and, under certain conditions, may show smaller finite-size corrections. PMID- 26274152 TI - Classical lattice spin models involving singular interactions isotropic in spin space. AB - We address here a few classical lattice spin models, involving n-component unit vectors (n=2,3), associated with a D-dimensional lattice Z(D),D=1,2, and interacting via a pair potential restricted to nearest neighbors and being isotropic in spin space, i.e., defined by a function of the scalar product between the interacting spins. When the potential involves a continuous function of the scalar product, the Mermin-Wagner theorem and its generalizations exclude orientational order at all finite temperatures in the thermodynamic limit, and exclude phase transitions at finite temperatures when D=1; on the other hand, we have considered here some comparatively simple functions of the scalar product which are bounded from below, diverge to +infinity for certain mutual orientations, and are continuous almost everywhere with integrable singularities. Exact solutions are presented for D=1, showing an absence of phase transitions and an absence of orientational order at all finite temperatures in the thermodynamic limit; for D=2, and in the absence of more stringent mathematical results, extensive simulations carried out on some of them point to the absence of orientational order at all finite temperatures and suggest the existence of a Berezinskii-Kosterlitz-Thouless transition. PMID- 26274153 TI - Small quantum absorption refrigerator with reversed couplings. AB - Small quantum absorption refrigerators have recently attracted renewed attention. Here we present a missing design of a two-qubit fridge, the main feature of which is that one of the two machine qubits is itself maintained at a temperature colder than the cold bath. This is achieved by "reversing" the couplings to the baths compared to previous designs, where only a transition is maintained cold. We characterize the working regime and the efficiency of the fridge. We demonstrate the soundness of the model by deriving and solving a master equation. Finally, we discuss the performance of the fridge, in particular the heat current extracted from the cold bath. We show that our model performs comparably to the standard three-level quantum fridge and thus appears appealing for possible implementations of nanoscale thermal machines. PMID- 26274154 TI - Dynamical approach to weakly dissipative granular collisions. AB - Granular systems present surprisingly complicated dynamics. In particular, nonlinear interactions and energy dissipation play important roles in these dynamics. Usually (but admittedly not always), constant coefficients of restitution are introduced phenomenologically to account for energy dissipation when grains collide. The collisions are assumed to be instantaneous and to conserve momentum. Here, we introduce the dissipation through a viscous (velocity dependent) term in the equations of motion for two colliding grains. Using a first-order approximation, we solve the equations of motion in the low viscosity regime. This approach allows us to calculate the collision time, the final velocity of each grain, and a coefficient of restitution that depends on the relative velocity of the grains. We compare our analytic results with those obtained by numerical integration of the equations of motion and with exact ones obtained by other methods for some geometries. PMID- 26274155 TI - Pattern formation in wet granular matter under vertical vibrations. AB - Experiments on a thin layer of cohesive wet granular matter under vertical vibrations reveal kink-separated domains that collide with the container at different phases. Due to the strong cohesion arising from the formation of liquid bridges between adjacent particles, the domains move collectively upon vibrations. Depending on the periodicity of this collective motion, the kink fronts may propagate, couple with each other, and form rotating spiral patterns in the case of period tripling or stay as standing wave patterns in the case of period doubling. Moreover, both patterns may coexist with granular "gas bubbles" phase separation into a liquidlike and a gaslike state. Stability diagrams for the instabilities measured with various granular layer mass m and container height H are presented. The onsets for both types of patterns and their dependency on m and H can be quantitatively captured with a model considering the granular layer as a single particle colliding completely inelastically with the container. PMID- 26274156 TI - Active dipole clusters: From helical motion to fission. AB - The structure of a finite particle cluster is typically determined by total energy minimization. Here we consider the case where a cluster of soft-sphere dipoles becomes active, i.e., when the individual particles exhibit an additional self-propulsion along their dipole moments. We numerically solve the overdamped equations of motion for soft-sphere dipoles in a solvent. Starting from an initial metastable dipolar cluster, the self-propulsion generates a complex cluster dynamics. The final cluster state has in general a structure widely different to the initial one, the details depend on the model parameters and on the protocol of how the self-propulsion is turned on. The center of mass of the cluster moves on a helical path, the details of which are governed by the initial cluster magnetization. An instantaneous switch to a high self-propulsion leads to fission of the cluster. However, fission does not occur if the self-propulsion is increased slowly to high strengths. Our predictions can be verified through experiments with self-phoretic colloidal Janus particles and for macroscopic self propelled dipoles in a highly viscous solvent. PMID- 26274157 TI - Dynamics of three-dimensional vesicles in dc electric fields. AB - A numerical and systematic parameter study of three-dimensional vesicle electrohydrodynamics is presented to investigate the effects of varying electric field strength and different fluid and membrane properties. The dynamics of vesicles in the presence of dc electric fields is considered, in both the presence and absence of linear shear flow. For suspended vesicles it is shown that the conductivity ratio and viscosity ratio between the interior and exterior fluids, as well as the vesicle membrane capacitance, substantially affect the minimum electric field strength required to induce a full prolate-oblate-prolate transition. In addition, there exists a critical electric field strength above which a vesicle will no longer tumble when exposed to linear shear flow. PMID- 26274158 TI - Phase formation in colloidal systems with tunable interaction. AB - Self-assembly is one of the most fascinating phenomena in nature and is one key component in the formation of hierarchical structures. The formation of structures depends critically on the interaction between the different constituents, and therefore the link between these interactions and the resulting structure is fundamental for the understanding of materials. We have realized a two-dimensional system of colloidal particles with tunable magnetic dipole forces. The phase formation is studied by transmission optical microscopy and a phase diagram is constructed. We report a phase transition from hexagonal to random and square arrangements when the magnetic interaction between the individual particles is tuned from antiferromagnetic to ferrimagnetic. PMID- 26274159 TI - Trapping of interacting propelled colloidal particles in inhomogeneous media. AB - A trapping mechanism for propelled colloidal particles based on an inhomogeneous drive is presented and studied by means of computer simulations. In experiments this method can be realized using photophoretic Janus particles driven by a light source, which is partially blocked by a shading mask. This leads to an accumulation of particles in the passive part. An equation for an accumulation parameter is derived using the effective inhomogeneous diffusion constant generated by the inhomogeneous drive. The impact of particle interaction on the trapping mechanism is studied, as well as the interplay between passivity-induced trapping and the emergent self-clustering of systems containing a high density of active particles. The combination of both effects makes the clusters more controllable for applications. PMID- 26274160 TI - Universal rescaling of flow curves for yield-stress fluids close to jamming. AB - The experimental flow curves of four different yield-stress fluids with different interparticle interactions are studied near the jamming concentration. By appropriate scaling with the distance to jamming all rheology data can be collapsed onto master curves below and above jamming that meet in the shear thinning regime and satisfy the Herschel-Bulkley and Cross equations, respectively. In spite of differing interactions in the different systems, master curves characterized by universal scaling exponents are found for the four systems. A two-state microscopic theory of heterogeneous dynamics is presented to rationalize the observed transition from Herschel-Bulkley to Cross behavior and to connect the rheological exponents to microscopic exponents for the divergence of the length and time scales of the heterogeneous dynamics. The experimental data and the microscopic theory are compared with much of the available literature data for yield-stress systems. PMID- 26274161 TI - Anisotropy of magnetoviscous effect in structure-forming ferrofluids. AB - The magnetoviscous effect, change in viscosity with change in magnetic field strength, and the anisotropy of the magnetoviscous effect, change in viscosity with orientation of magnetic field, have been a focus of interest for four decades. A satisfactory understanding of the microscopic origin of anisotropy of the magnetoviscous effect in magnetic fluids is still a matter of debate and a field of intense research. Here, we present an extensive simulation study to understand the relation between the anisotropy of the magnetoviscous effect and the underlying change in microstructures of ferrofluids. Our results indicate that field-induced chainlike structures respond very differently depending on their orientation relative to the direction of an externally applied shear flow, which leads to a pronounced anisotropy of viscosity. In this work, we focus on three exemplary values of dipolar interaction strengths which correspond to weak, intermediate, and strong interactions between dipolar colloidal particles. We compare our simulation results with an experimental study on cobalt-based ferrofluids as well as with an existing theoretical model called the chain model. A nonmonotonic behavior in the anisotropy of the magnetoviscous effect is observed with increasing dipolar interaction strength and is explained in terms of microstructure formation. PMID- 26274162 TI - Transition from hydrodynamic to viscoelastic propagation of sound in molten RbBr. AB - Inelastic neutron scattering was applied to measure the acoustic-type excitations in the molten alkali halide rubidium bromide. For molten RbBr neutron scattering is mainly sensitive to the number density fluctuation spectrum and is not influenced by charge fluctuations. Utilizing a dedicated Brillouin scattering spectrometer, we focused on the small-wave-vector range. From inelastic excitations in the spectra a dispersion relation was obtained, which shows a large positive dispersion effect. This frequency enhancement is related to a viscoelastic response of the liquid at high frequencies. Towards small wave vectors we identify the transition to hydrodynamic behavior. This observation is supported by a transition of the sound velocity from a viscoelastic enhanced value to the adiabatic speed of sound for the acoustic-type excitations. Furthermore, the spectrum transforms into a line shape compatible with a prediction from hydrodynamics. PMID- 26274163 TI - Chromatic patchy particles: Effects of specific interactions on liquid structure. AB - We study the structural and thermodynamic properties of patchy particle liquids, with a special focus on the role of "color," i.e., specific interactions between individual patches. A possible experimental realization of such "chromatic" interactions is by decorating the particle patches with single-stranded DNA linkers. The complementarity of the linkers can promote selective bond formation between predetermined pairs of patches. By using MD simulations, we compare the local connectivity, the bond orientation order, and other structural properties of the aggregates formed by the "colored" and "colorless" systems. The analysis is done for spherical particles with two different patch arrangements (tetrahedral and cubic). It is found that the aggregated (liquid) phase of the "colorless" patchy particles is better connected, denser and typically has stronger local order than the corresponding "colored" one. This, in turn, makes the colored liquid less stable thermodynamically. Specifically, we predict that in a typical case the chromatic interactions should increase the relative stability of the crystalline phase with respect to the disordered liquid, thus expanding its region in the phase diagram. PMID- 26274164 TI - Thermal fluctuations, mechanical response, and hyperuniformity in jammed solids. AB - Jamming is a geometric phase transition occurring in dense particle systems in the absence of temperature. We use computer simulations to analyze the effect of thermal fluctuations on several signatures of the transition. We show that scaling laws for bulk and shear moduli only become relevant when thermal fluctuations are extremely small, and propose their relative ratio as a quantitative signature of jamming criticality. Despite the nonequilibrium nature of the transition, we find that thermally induced fluctuations and mechanical responses obey equilibrium fluctuation-dissipation relations near jamming, provided the appropriate fluctuating component of the particle displacements is analyzed. This shows that mechanical moduli can be directly measured from particle positions in mechanically unperturbed packings, and suggests that the definition of a "nonequilibrium index" is unnecessary for amorphous materials. We find that fluctuations of particle displacements are spatially correlated, and define a transverse and a longitudinal correlation length scale which both diverge as the jamming transition is approached. We analyze the frozen component of density fluctuations and find that it displays signatures of nearly hyperuniform behavior at large length scales. This demonstrates that hyperuniformity in jammed packings is unrelated to a vanishing compressibility and explains why it appears remarkably robust against temperature and density variations. Differently from jamming criticality, obstacles preventing the observation of hyperuniformity in colloidal systems do not originate from thermal fluctuations. PMID- 26274165 TI - Effect of boundary conditions on the character of ambipolar diffusion in electrolytes. AB - We discuss the details of ambipolar relaxation of the electric field in liquid asymmetric electrolytes to its stationary value. It is demonstrated that the account for finite boundary conditions modifies the existing concepts of this diffusion process. In particular, we succeeded to suggest a qualitatively correct explanation of the observed distribution of the electric fields over the bulk of the cuvette and its nonmonotonic behavior in measurements on the finite-size cuvette. We analyze the conditions of such an anomaly at the intermediate stages of the relaxation process. PMID- 26274166 TI - Hydrogen self-dynamics in liquid H(2)-D(2) mixtures studied through inelastic neutron scattering. AB - We have measured the dynamic structure factor of liquid para-hydrogen mixed with normal deuterium (T=20 K) at two different concentration levels using incoherent inelastic neutron scattering. This choice has been made since the presence of D(2} modifies the self-dynamics of H(2) in a highly nontrivial way, acting both on its pseudophononic and its diffusive parts in a tunable way. After an accurate data reduction, recorded neutron spectra were studied through the modified Young and Koppel model and the H(2) center-of-mass self-dynamics structure factor was finally extracted for the two mixtures. Some physical quantities (i.e., self diffusion coefficient and mean kinetic energy) were determined and compared with accurate quantum calculations, which, in addition, also provided estimates of the velocity autocorrelation function for the H(2) centers of mass. These estimates, in conjunction with the Gaussian approximation, were used to simulate the H(2) center-of-mass self-dynamics structure factor in the same range as the experimental one. The agreement between measured and calculated spectra was globally good, but some discrepancies proved the unquestionable breakdown of the Gaussian approximation in these semiquantum systems at a level comparable to that already observed in pure liquid para-hydrogen. PMID- 26274167 TI - Pore-size dependence and characteristics of water diffusion in slitlike micropores. AB - The temperature dependence of the dynamics of water inside microporous activated carbon fibers (ACF) is investigated by means of incoherent elastic and quasielastic neutron-scattering techniques. The aim is to evaluate the effect of increasing pore size on the water dynamics in these primarily hydrophobic slit shaped channels. Using two different micropore sizes (~12 and 18 A, denoted, respectively, ACF-10 and ACF-20), a clear suppression of the mobility of the water molecules is observed as the pore gap or temperature decreases. This suppression is accompanied by a systematic dependence of the average translational diffusion coefficient D(r) and relaxation time of the restricted water on pore size and temperature. The observed D(r) values are tested against a proposed scaling law, in which the translational diffusion coefficient D(r) of water within a porous matrix was found to depend solely on two single parameters, a temperature-independent translational diffusion coefficient D(c) associated with the water bound to the pore walls and the ratio theta of this strictly confined water to the total water inside the pore, yielding unique characteristic parameters for water transport in these carbon channels across the investigated temperature range. PMID- 26274168 TI - Bimodal colloid gels of highly size-asymmetric particles. AB - We report a type of colloidal gel, induced by a minute incremental addition of mutually attractive small particles (size ~12 nm) to a suspension of highly charged large particles (size ~500 nm). The gel's morphological behavior does not follow the typical power-law scaling for fractal clusters. Its unique scaling behavior has two distinct power-law indices, based on particle volume fraction. We show the unique scaling behavior arises when nonfractal networks of large particles are bridged by small-particle clusters, which occurs between a lower and upper critical boundary of small particle volume fraction. PMID- 26274169 TI - Anomalous dynamics of an elastic membrane in an active fluid. AB - Using numerical simulations, we characterized the behavior of an elastic membrane immersed in an active fluid. Our findings reveal a nontrivial folding and re expansion of the membrane that is controlled by the interplay of its resistance to bending and the self-propulsion strength of the active components in solution. We show how flexible membranes tend to collapse into multifolded states, whereas stiff membranes fluctuate between an extended configuration and a singly folded state. This study provides a simple example of how to exploit the random motion of active particles to perform mechanical work at the microscale. PMID- 26274170 TI - Numerical detection of the Gardner transition in a mean-field glass former. AB - Recent theoretical advances predict the existence, deep into the glass phase, of a novel phase transition, the so-called Gardner transition. This transition is associated with the emergence of a complex free energy landscape composed of many marginally stable sub-basins within a glass metabasin. In this study, we explore several methods to detect numerically the Gardner transition in a simple structural glass former, the infinite-range Mari-Kurchan model. The transition point is robustly located from three independent approaches: (i) the divergence of the characteristic relaxation time, (ii) the divergence of the caging susceptibility, and (iii) the abnormal tail in the probability distribution function of cage order parameters. We show that the numerical results are fully consistent with the theoretical expectation. The methods we propose may also be generalized to more realistic numerical models as well as to experimental systems. PMID- 26274172 TI - Shear-transformation-zone theory of yielding in athermal amorphous materials. AB - Yielding transitions in athermal amorphous materials undergoing steady-state shear flow resemble critical phenomena. Historically, they have been described by the Herschel-Bulkley rheological formula, which implies singular behaviors at yield points. In this paper, I examine this class of phenomena using an elementary version of the thermodynamic shear-transformation-zone (STZ) theory, focusing on the role of the effective disorder temperature, and paying special attention to scaling and dimensional arguments. I find a wide variety of Herschel Bulkley-like rheologies but, for fundamental reasons not specific to the STZ theory, conclude that the yielding transition is not truly critical. In particular, for realistic many-body models with short-range interactions, there is a correlation length that grows rapidly but ultimately saturates near the yield point. PMID- 26274171 TI - Suppression of Ostwald ripening in active emulsions. AB - Emulsions consisting of droplets immersed in a fluid are typically unstable since they coarsen over time. One important coarsening process is Ostwald ripening, which is driven by the surface tension of the droplets. Stability of emulsions is relevant not only in complex fluids but also in biological cells, which contain liquidlike compartments, e.g., germ granules, Cajal bodies, and centrosomes. Such cellular systems are driven away from equilibrium, e.g., by chemical reactions, and thus can be called active emulsions. In this paper, we study such active emulsions by developing a coarse-grained description of the droplet dynamics, which we analyze for two different chemical reaction schemes. We first consider the simple case of first-order reactions, which leads to stable, monodisperse emulsions in which Ostwald ripening is suppressed within a range of chemical reaction rates. We then consider autocatalytic droplets, which catalyze the production of their own droplet material. Spontaneous nucleation of autocatalytic droplets is strongly suppressed and their emulsions are typically unstable. We show that autocatalytic droplets can be nucleated reliably and their emulsions stabilized by the help of chemically active cores, which catalyze the production of droplet material. In summary, different reaction schemes and catalytic cores can be used to stabilize emulsions and to control their properties. PMID- 26274173 TI - Cooling the two-dimensional short spherocylinder liquid to the tetratic phase: Heterogeneous dynamics with one-way coupling between rotational and translational hopping. AB - We numerically demonstrate the transition from the isotropic liquid to the tetratic phase with quasilong-range tetratic alignment order (i.e., with nearly parallel or perpendicular aligned rods), for the cold two-dimensional (2D) short spherocylinder system before crystallization and investigate the thermal assisted heterogeneous rotational and translational micromotions. Comparing with the 2D liquid of isotropic particles, spherocylinders introduce extra rotational degrees of freedom and destroy packing isotropy and the equivalence between rotational and translational motions. It is found that cooling leads to the stronger dynamical heterogeneity with more cooperative hopping and the stronger retardations of rotational hopping than translational hopping. Under topological constraints from nearly parallel and perpendicular rods of the tetratic phase, longitudinal and transverse translational hopping can occur without rotational hopping, but not the reverse. The empty space trailing a neighboring translational hopping patch is needed for triggering the patch rotational hopping with its translational motion into the empty space. It is the origin for the observed increasing separation of hopping time scales and the one-way coupling between rotational and translational hopping. Strips of longitudinally or transversely aligned rods can be ruptured and reconnected with neighboring strips through buckling, kink formation, and patch rotation, under the unbalanced torques or forces from their neighboring rods and thermal kicks. PMID- 26274174 TI - Cooling rate and stress relaxation in silica melts and glasses via microsecond molecular dynamics. AB - We have conducted extremely long molecular dynamics simulations of glasses to microsecond times, which close the gap between experimental and atomistic simulation time scales by two to three orders of magnitude. Static, thermal, and structural properties of silica glass are reported for glass cooling rates down to 5*10(9) K/s and viscoelastic response in silica melts and glasses are studied over nine decades of time. We present results from relaxation of hydrostatic compressive stress in silica and show that time-temperature superposition holds in these systems for temperatures from 3500 to 1000 K. PMID- 26274175 TI - Systematic interpretation of differential capacitance data. AB - Differential capacitance (DC) data have been widely used to characterize the structure of electrolyte solutions near charged interfaces and as experimental validation of models for electrolyte structure. Fixing a large class of models of electrolyte free energy that incorporate finite-volume effects, a reduction is identified which permits the identification of all free energies within that class that return identical DC data. The result is an interpretation of DC data through the equivalence classes of nonideality terms, and associated boundary layer structures, that cannot be differentiated by DC data. Specifically, for binary salts, DC data, even if measured over a range of ionic concentrations, are unable to distinguish among models which exhibit charge asymmetry, charge reversal, and even ion crowding. The reduction applies to capacitors which are much wider than the associated Debye length and to finite-volume terms that are algebraic in charge density. However, within these restrictions the free energy is shown to be uniquely identified if the DC data are supplemented with measurements of the excess chemical potential of the system in the bulk state. PMID- 26274176 TI - Self-propelled rods exhibit a phase-separated state characterized by the presence of active stresses and the ejection of polar clusters. AB - We study collections of self-propelled rods (SPR) moving in two dimensions for packing fractions less than or equal to 0.3. We find that in the thermodynamical limit the SPR undergo a phase transition between a disordered gas and a novel phase-separated system state. Interestingly, (global) orientational order patterns-contrary to what has been suggested-vanish in this limit. In the found novel state, the SPR self-organize into a highly dynamical, high-density, compact region-which we call aggregate-which is surrounded by a disordered gas. Active stresses build inside aggregates as a result of the combined effect of local orientational order and active forces. This leads to the most distinctive feature of these aggregates: constant ejection of polar clusters of SPR. This novel phase separated state represents a novel state of matter characterized by large fluctuations in volume and shape, related to mass ejection, and exhibits positional as well as orientational local order. SPR systems display new physics unseen in other active matter systems. PMID- 26274177 TI - Segregation of oppositely driven colloidal particles in hard-walled channels: A finite-size study. AB - We investigate segregation phenomena of particles driven in opposite directions with Brownian dynamics simulations. The particles interact via a repulsive potential and are confined in three-dimensional hard-walled pipes with quadratic cross sections. In a systematic finite-size study, the pipe length is varied. Ordering on finite length scales can be observed, but global segregation seems to vanish for infinite channel length, as it was recently found for lane formation in two dimensions. As an additional effect of the finite hard-walled boundary conditions, interface vibrations and longitudinal demixing are found. PMID- 26274178 TI - Soft-core particles freezing to form a quasicrystal and a crystal-liquid phase. AB - Systems of soft-core particles interacting via a two-scale potential are studied. The potential is responsible for peaks in the structure factor of the liquid state at two different but comparable length scales and a similar bimodal structure is evident in the dispersion relation. Dynamical density functional theory in two dimensions is used to identify two unusual states of this system: a crystal-liquid state, in which the majority of the particles are located on lattice sites but a minority remains free and so behaves like a liquid, and a 12 fold quasicrystalline state. Both are present even for deeply quenched liquids and are found in a regime in which the liquid is unstable with respect to modulations on the smaller scale only. As a result, the system initially evolves towards a small-scale crystal state; this state is not a minimum of the free energy, however, and so the system subsequently attempts to reorganize to generate the lower-energy larger-scale crystals. This dynamical process generates a disordered state with quasicrystalline domains and takes place even when this large scale is linearly stable, i.e., it is a nonlinear process. With controlled initial conditions, a perfect quasicrystal can form. The results are corroborated using Brownian dynamics simulations. PMID- 26274179 TI - Renormalized dynamics of the Dean-Kawasaki model. AB - We study the model of a supercooled liquid for which the equation of motion for the coarse-grained density rho(x,t) is the nonlinear diffusion equation originally proposed by Dean and Kawasaki, respectively, for Brownian and Newtonian dynamics of fluid particles. Using a Martin-Siggia-Rose (MSR) field theory we study the renormalization of the dynamics in a self-consistent form in terms of the so-called self-energy matrix Sigma. The appropriate model for the renormalized dynamics involves an extended set of field variables {rho,theta}, linked through a nonlinear constraint. The latter incorporates, in a nonperturbative manner, the effects of an infinite number of density nonlinearities in the dynamics. We show that the contributing element of Sigma which renormalizes the bare diffusion constant D(0) to D(R) is same as that proposed by Kawasaki and Miyazima [Z. Phys. B Condens. Matter 103, 423 (1997)]. D(R) sharply decreases with increasing density. We consider the likelihood of a ergodic-nonergodic (ENE) transition in the model beyond a critical point. The transition is characterized by the long-time limit of the density correlation freezing at a nonzero value. From our analysis we identify an element of Sigma which arises from the above-mentioned nonlinear constraint and is key to the viability of the ENE transition. If this self-energy would be zero, then the model supports a sharp ENE transition with D(R)=0 as predicted by Kawasaki and Miyazima. With the full model having nonzero value for this self-energy, the density autocorrelation function decays to zero in the long-time limit. Hence the ENE transition is not supported in the model. PMID- 26274180 TI - Exceptional stiffening in composite fiber networks. AB - We study the small strain elastic behavior of composite athermal fiber networks constructed by adding stiffer fibers to a cross-linked base network. We observe that if the base network is in the affine deformation regime, the composite behaves similar to a fiber-reinforced continuum. When the base network is in the nonaffine deformation regime, the stiffness of the composite increases by orders of magnitude upon the addition of a small fraction of stiff fibers. The increase is not gradual, but rather occurs in two steps. Of these, one is associated with the stiffness percolation of the network of added fibers. The other, which occurs at very small fractions of stiff fibers, is due to the percolation of perturbation zones, or "interphases," induced in the base network by the stiff fibers, regions where the energy is stored mostly in the axial deformation mode. Their size controls the stiffening transition and depends on base network parameters and the length of added fibers. It is also shown that the perturbation field introduced in the base network by the presence of a stiff fiber is much longer ranged than in the case when the fiber is tied to a continuum of same modulus with the base network. PMID- 26274181 TI - Transition from compact to porous films in deposition with temperature-activated diffusion. AB - We study a thin-film growth model with temperature activated diffusion of adsorbed particles, allowing for the formation of overhangs and pores, but without detachment of adatoms or clusters from the deposit. Simulations in one dimensional substrates are performed for several values of the diffusion-to deposition ratio R of adatoms with a single bond and of the detachment probability epsilon per additional nearest neighbor, respectively, with activation energies are E(s) and E(b). If R and epsilon independently vary, regimes of low and high porosity are separated at 0.075<=epsilon(c)<=0.09, with vanishingly small porosity below that point and finite porosity for larger epsilon. Alternatively, for fixed values of E(s) and E(b) and varying temperature, the porosity has a minimum at T(c), and a nontrivial regime in which it increases with temperature is observed above that point. This is related to the large mobility of adatoms, resembling features of equilibrium surface roughening. In this high-temperature region, the deposit has the structure of a critical percolation cluster due to the nondesorption. The pores are regions enclosed by blobs of the corresponding percolating backbone, thus the distribution of pore size s is expected to scale as s(-tau) with tau~1.45, in reasonable agreement with numerical estimates. Roughening of the outer interface of the deposits suggests Villain-Lai-Das Sarma scaling below the transition. Above the transition, the roughness exponent alpha~0.35 is consistent with the percolation backbone structure via the relation alpha=2-d(B), where d(B) is the backbone fractal dimension. PMID- 26274182 TI - Microbranching in mode-I fracture using large-scale simulations of amorphous and perturbed-lattice models. AB - We study the high-velocity regime mode-I fracture instability wherein small microbranches start to appear near the main crack, using large-scale simulations. Some of the features of those microbranches have been reproduced qualitatively in smaller-scale studies [using O(10(4)) atoms] on both a model of an amorphous material (via the continuous random network model) and using perturbed-lattice models. In this study, larger-scale simulations [O(10(6)) atoms] were performed using multithreading computing on a GPU device, in order to achieve more physically realistic results. First, we find that the microbranching pattern appears to be converging with the lattice width. Second, the simulations reproduce the growth of the size of a microbranch as a function of the crack velocity, as well as the increase of the amplitude of the derivative of the electrical-resistance root-mean square with respect to the time as a function of the crack velocity. In addition, the simulations yield the correct branching angle of the microbranches, and the power law exponent governing the shape of the microbranches seems to be lower than unity, so that the side cracks turn over in the direction of propagation of the main crack as seen in experiment. PMID- 26274183 TI - Diffusion-controlled growth rate of stepped interfaces. AB - For many materials, the structure of crystalline surfaces or solid-solid interphase boundaries is characterized by an array of mobile steps separated by immobile terraces. Despite the prevalence of step-terraced interfaces a theoretical description of the growth rate has not been completely solved. In this work the boundary element method (BEM) has been utilized to numerically compute the concentration profile in a fluid phase in contact with an infinite array of equally spaced surface steps and, under the assumption that step motion is controlled by diffusion through the fluid phase, the growth rate is computed. It is also assumed that a boundary layer exists between the growing surface and a point in the liquid where complete convective mixing occurs. The BEM results are presented for varying step spacing, supersaturation, and boundary layer width. BEM calculations were also used to study the phenomenon of step bunching during crystal growth, and it is found that, in the absence of elastic strain energy, a sufficiently large perturbation in the position of a step from its regular spacing will lead to a step bunching instability. Finally, an approximate analytic solution using a matched asymptotic expansion technique is presented for the case of a stagnant liquid or equivalently a solid-solid stepped interface. PMID- 26274184 TI - Equilibrium shapes of planar elastic membranes. AB - Using a rod theory formulation, we derive equations of state for a thin elastic membrane subjected to several different boundary conditions-clamped, simply supported, and periodic. The former is applicable to membranes supported on a softer substrate and subjected to uniaxial compression. We show that a wider family of quasistatic equilibrium shapes exist beyond the previously obtained analytical solutions. In the latter case of periodic membranes, we were able to derive exact solutions in terms of elliptic functions. These equilibria are verified by considering a fluid-structure interaction problem of a periodic, length-preserving bilipid membrane modeled by the Helfrich energy immersed in a viscous fluid. Starting from an arbitrary shape, the membrane dynamics to equilibrium are simulated using a boundary integral method. PMID- 26274185 TI - Controlling the wetting transitions of nanoparticles on nanopatterned substrates using an electric current. AB - We study the behavior of a nanoparticle under electromigration on a nanopatterned surface. We show that electromigration allows one to control the wetting transitions of the nanoparticle. Suitable surface electromigration conditions to observe these transitions can be achieved with electric currents larger than 1 MUA. Using kinetic Monte Carlo simulations and analytical modeling, we determine the phase diagram of the wetting states, showing how wetting multistability is affected by electromigration. In addition, we show that the dynamics of the transitions is controlled by surface diffusion in our simulations, and we provide a quantitative expression for the transition time. PMID- 26274186 TI - Frictional dynamics of viscoelastic solids driven on a rough surface. AB - We study the effect of viscoelastic dynamics on the frictional properties of a (mean-field) spring-block system pulled on a rough surface by an external drive. When the drive moves at constant velocity V, two dynamical regimes are observed: at fast driving, above a critical threshold V(c), the system slides at the drive velocity and displays a friction force with velocity weakening. Below V(c) the steady sliding becomes unstable and a stick-slip regime sets in. In the slide hold-slide driving protocol, a peak of the friction force appears after the hold time and its amplitude increases with the hold duration. These observations are consistent with the frictional force encoded phenomenologically in the rate-and state equations. Our model gives a microscopical basis for such macroscopic description. PMID- 26274187 TI - Speed of fast and slow rupture fronts along frictional interfaces. AB - The transition from stick to slip at a dry frictional interface occurs through the breaking of microjunctions between the two contacting surfaces. Typically, interactions between junctions through the bulk lead to rupture fronts propagating from weak and/or highly stressed regions, whose junctions break first. Experiments find rupture fronts ranging from quasistatic fronts, via fronts much slower than elastic wave speeds, to fronts faster than the shear wave speed. The mechanisms behind and selection between these fronts are still imperfectly understood. Here we perform simulations in an elastic two-dimensional spring-block model where the frictional interaction between each interfacial block and the substrate arises from a set of junctions modeled explicitly. We find that material slip speed and rupture front speed are proportional across the full range of front speeds we observe. We revisit a mechanism for slow slip in the model and demonstrate that fast slip and fast fronts have a different, inertial origin. We highlight the long transients in front speed even along homogeneous interfaces, and we study how both the local shear to normal stress ratio and the local strength are involved in the selection of front type and front speed. Last, we introduce an experimentally accessible integrated measure of block slip history, the Gini coefficient, and demonstrate that in the model it is a good predictor of the history-dependent local static friction coefficient of the interface. These results will contribute both to building a physically based classification of the various types of fronts and to identifying the important mechanisms involved in the selection of their propagation speed. PMID- 26274188 TI - Rotation-limited growth of three-dimensional body-centered-cubic crystals. AB - According to classical grain growth laws, grain growth is driven by the minimization of surface energy and will continue until a single grain prevails. These laws do not take into account the lattice anisotropy and the details of the microscopic rearrangement of mass between grains. Here we consider coarsening of body-centered-cubic polycrystalline materials in three dimensions using the phase field crystal model. We observe, as a function of the quenching depth, a crossover between a state where grain rotation halts and the growth stagnates and a state where grains coarsen rapidly by coalescence through rotation and alignment of the lattices of neighboring grains. We show that the grain rotation per volume change of a grain follows a power law with an exponent of -1.25. The scaling exponent is consistent with theoretical considerations based on the conservation of dislocations. PMID- 26274189 TI - Nematic liquid crystals in planar and cylindrical hybrid cells: Role of elastic anisotropy on the director deformations. AB - Nematic samples filling a flat cell or the annular region between two concentric cylinders with hybrid anchoring conditions at the boundaries are investigated by setting up and minimizing their Frank elastic free energy. The coupling with the surfaces is taken to be strong on one side and weak on the other. The equations are numerically solved and the conditions for which the molecular organization inside the cell becomes uniform are analyzed. The classical calculation performed by G. Barbero and R. Barberi [J. Phys. 44, 609 (1983)] is reproduced and investigated from a different point of view, in order to compare the results of planar and cylindrical geometries. The results suggest that the cylindrical cell presents some unusual features deserving a more complete investigation. Although most part of the transitional phenomena are found for K(11)>K(33), a case not common for ordinary (lyotropic and thermotropic) liquid crystals, it is possible to find a completely uniform cell even for K(11)=16-mers it is between three states. We also calculate the structural fluctuations for all of the denatured states and find that the denatured states contain a broad range of incompletely unfolded conformations, similar to "molten globule" states referred to in acid or alkaline denatured real proteins. These results show that the proposed model provides a simple physical picture of pH induced protein denaturation. PMID- 26274206 TI - Inherently unstable networks collapse to a critical point. AB - Nonequilibrium systems that are driven or drive themselves towards a critical point have been studied for almost three decades. Here we present a minimalist example of such a system, motivated by experiments on collapsing active elastic networks. Our model of an unstable elastic network exhibits a collapse towards a critical point from any macroscopically connected initial configuration. Taking into account steric interactions within the network, the model qualitatively and quantitatively reproduces results of the experiments on collapsing active gels. PMID- 26274207 TI - Numerical methods for a Poisson-Nernst-Planck-Fermi model of biological ion channels. AB - Numerical methods are proposed for an advanced Poisson-Nernst-Planck-Fermi (PNPF) model for studying ion transport through biological ion channels. PNPF contains many more correlations than most models and simulations of channels, because it includes water and calculates dielectric properties consistently as outputs. This model accounts for the steric effect of ions and water molecules with different sizes and interstitial voids, the correlation effect of crowded ions with different valences, and the screening effect of polarized water molecules in an inhomogeneous aqueous electrolyte. The steric energy is shown to be comparable to the electrical energy under physiological conditions, demonstrating the crucial role of the excluded volume of particles and the voids in the natural function of channel proteins. Water is shown to play a critical role in both correlation and steric effects in the model. We extend the classical Scharfetter-Gummel (SG) method for semiconductor devices to include the steric potential for ion channels, which is a fundamental physical property not present in semiconductors. Together with a simplified matched interface and boundary (SMIB) method for treating molecular surfaces and singular charges of channel proteins, the extended SG method is shown to exhibit important features in flow simulations such as optimal convergence, efficient nonlinear iterations, and physical conservation. The generalized SG stability condition shows why the standard discretization (without SG exponential fitting) of NP equations may fail and that divalent Ca(2+) may cause more unstable discrete Ca(2+) fluxes than that of monovalent Na(+). Two different methods-called the SMIB and multiscale methods are proposed for two different types of channels, namely, the gramicidin A channel and an L-type calcium channel, depending on whether water is allowed to pass through the channel. Numerical methods are first validated with constructed models whose exact solutions are known. The experimental data of both channels are then used to verify and explain novel features of PNPF as compared with previous PNP models. The PNPF currents are in accord with the experimental I-V (V for applied voltages) data of the gramicidin A channel and I-C (C for bath concentrations) data of the calcium channel with 10(-8)-fold bath concentrations that pose severe challenges in theoretical simulations. PMID- 26274208 TI - Two-population model for medial temporal lobe neurons: The vast majority are almost silent. AB - Recordings in the human medial temporal lobe have found many neurons that respond to pictures (and related stimuli) of just one particular person of those presented. It has been proposed that these are concept cells, responding to just a single concept. However, a direct experimental test of the concept cell idea appears impossible, because it would need the measurement of the response of each cell to enormous numbers of other stimuli. Here we propose a new statistical method for analysis of the data that gives a more powerful way to analyze how close data are to the concept-cell idea. Central to the model is the neuronal sparsity, defined as the total fraction of stimuli that elicit an above-threshold response in the neuron. The model exploits the large number of sampled neurons to give sensitivity to situations where the average response sparsity is much less than one response for the number of presented stimuli. We show that a conventional model where a single sparsity is postulated for all neurons gives an extremely poor fit to the data. In contrast, a model with two dramatically different populations gives an excellent fit to data from the hippocampus and entorhinal cortex. In the hippocampus, one population has 7% of the cells with a 2.6% sparsity. But a much larger fraction (93%) respond to only 0.1% of the stimuli. This can result in an extreme bias in the responsiveness of reported neurons compared with a typical neuron. Finally, we show how to allow for the fact that some identified units correspond to multiple neurons and find that our conclusions at the neural level are quantitatively changed but strengthened, with an even stronger difference between the two populations. PMID- 26274209 TI - Collapse of DNA under alternating electric fields. AB - Recent studies have shown that double-stranded DNA can collapse in the presence of a strong electric field. Here we provide an in-depth study of the collapse of DNA under weak confinement in microchannels as a function of buffer strength, driving frequency, applied electric-field strength, and molecule size. We find that the critical electric field at which DNA molecules collapse (tens of kV/m) is strongly dependent on driving frequency (100-800 Hz) and molecular size (20 160 kbp), and weakly dependent on the ionic strength (8-60 mM). We argue that an apparent stretching at very high electric fields is an artifact of the finite frame time of video microscopy. PMID- 26274210 TI - Vesiculation of healthy and defective red blood cells. AB - Vesiculation of mature red blood cells (RBCs) contributes to removal of defective patches of the erythrocyte membrane. In blood disorders, which are related to defects in proteins of the RBC membrane, vesiculation of the plasma membrane is intensified. Several hypotheses have been proposed to explain RBC vesiculation but the exact underlying mechanisms and what determines the sizes of the vesicles are still not completely understood. In this work, we apply a two-component coarse-grained molecular dynamics RBC membrane model to study how RBC vesiculation is controlled by the membrane spontaneous curvature and by lateral compression of the membrane. Our simulation results show that the formation of small homogeneous vesicles with a diameter less than 40 nm can be attributed to a large spontaneous curvature of membrane domains. On the other hand, compression on the membrane can cause the formation of vesicles with heterogeneous composition and with sizes comparable with the size of the cytoskeleton corral. When spontaneous curvature and lateral compression are simultaneously considered, the compression on the membrane tends to facilitate formation of vesicles originating from curved membrane domains. We also simulate vesiculation of RBCs with membrane defects connected to hereditary elliptocytosis (HE) and to hereditary spherocytosis (HS). When the vertical connectivity between the lipid bilayer and the membrane skeleton is elevated, as in normal RBCs, multiple vesicles are shed from the compressed membrane with diameters similar to the cytoskeleton corral size. In HS RBCs, where the connectivity between the lipid bilayer and the cytoskeleton is reduced, larger-size vesicles are released under the same compression ratio as in normal RBCs. Lastly, we find that vesicles released from HE RBCs can contain cytoskeletal filaments due to fragmentation of the membrane skeleton while vesicles released from the HS RBCs are depleted of cytoskeletal filaments. PMID- 26274211 TI - Modeling the dynamics of a tracer particle in an elastic active gel. AB - The internal dynamics of active gels both in artificial (in vitro) model systems and inside the cytoskeleton of living cells has been extensively studied with experiments of recent years. These dynamics are probed using tracer particles embedded in the network of biopolymers together with molecular motors, and distinct nonthermal behavior is observed. We present a theoretical model of the dynamics of a trapped active particle, which allows us to quantify the deviations from equilibrium behavior, using both analytic and numerical calculations. We map the different regimes of dynamics in this system and highlight the different manifestations of activity: breakdown of the virial theorem and equipartition, different elasticity-dependent "effective temperatures," and distinct non Gaussian distributions. Our results shed light on puzzling observations in active gel experiments and provide physical interpretation of existing observations, as well as predictions for future studies. PMID- 26274212 TI - Fluctuations of red blood cell membranes: The role of the cytoskeleton. AB - We theoretically investigate the membrane fluctuations of red blood cells with focus laid on the role of the cytoskeleton, viewing the system as a membrane coupled to a sparse spring network. This model is exactly solvable and enables us to examine the coupling strength dependence of the membrane undulation. We find that the coupling modifies the fluctuation spectrum at wavelengths longer than the mesh size of the network, while leaving the fluid-like behavior of the membrane intact at shorter wavelengths. The fluctuation spectra can be markedly different, depending on not only the relative amplitude of the bilayer bending energy with respect to the cytoskeleton deformation energy but also the bilayer cytoskelton coupling strength. PMID- 26274213 TI - Analytical properties of a three-compartmental dynamical demographic model. AB - The three-compartmental demographic model by Korotaeyv-Malkov-Khaltourina, connecting population size, economic surplus, and education level, is considered from the point of view of dynamical systems theory. It is shown that there exist two integrals of motion, which enables the system to be reduced to one nonlinear ordinary differential equation. The study of its structure provides analytical criteria for the dominance ranges of the dynamics of Malthus and Kremer. Additionally, the particular ranges of parameters enable the derived general ordinary differential equations to be reduced to the models of Gompertz and Thoularis-Wallace. PMID- 26274214 TI - General formulation of Luria-Delbruck distribution of the number of mutants. AB - The Luria-Delbruck experiment is a cornerstone of evolutionary theory, demonstrating the randomness of mutations before selection. The distribution of the number of mutants in this experiment has been the subject of intense investigation during the past 70 years. Despite this considerable effort, most of the results have been obtained under the assumption of constant growth rate, which is far from the experimental condition. We derive here the properties of this distribution for arbitrary growth function for both the deterministic and stochastic growth of the mutants. The derivation we propose uses the number of wild-type bacteria as the independent variable instead of time. The derivation is surprisingly simple and versatile, allowing many generalizations to be taken easily into account. PMID- 26274215 TI - Environment-induced anisotropy and sensitivity of the radical pair mechanism in the avian compass. AB - Several experiments over the years have shown that the earth's magnetic field is essential for orientation in birds' migration. The most promising explanation for this orientation is the photo-stimulated radical pair (RP) mechanism. In order to define a reference frame for the orientation task radicals must have an intrinsic anisotropy. We show that this kind of anisotropy and consequently the entanglement in the model are not necessary for the proper functioning of the compass. Classically correlated initial conditions for the RP, subjected to a fast decoherence process, are able to provide the anisotropy required. Even a dephasing environment can provide the necessary frame for the compass to work and also implies fast decay of any quantum correlation in the system without damaging the orientation ability. This fact significantly expands the range of applicability of the RP mechanism providing more elements for experimental search. PMID- 26274216 TI - Fluctuation and noise propagation in phenotypic transition cascades of clonal populations. AB - Quantitative modeling of fluctuations of each phenotype is a crucial step towards a fundamental understanding of noise propagation through various phenotypic transition cascades. The theoretical formulas for noise propagation in various phenotypic transition cascades are derived by using the linear noise approximation of master equation and the logarithmic gain. By virtue of the theoretical formulas, we study the noise propagation in bidirectional and unidirectional phenotypic transition cascades, respectively. It is found that noise propagation in these two phenotypic transition cascades evidently differs: In the bidirectional cascade, a systemic random environment is provided by a correlated global component. The total noise of each phenotype is mainly determined by the intrinsic noise and the transmitted noise from other phenotypes. The intrinsic noise enlarged by interconversion through an added part shows a novel noise propagation mechanism. However, in the unidirectional cascade, the random environment of each downstream phenotype is provided by upstream phenotypes. The total noise of each downstream phenotype is mainly determined by the transmitted noises from upstream phenotypes. The intrinsic noise and the conversion noise can propagate in both bidirectional and unidirectional phenotypic transition cascades. PMID- 26274217 TI - Extinction dynamics of a discrete population in an oasis. AB - Understanding the conditions ensuring the persistence of a population is an issue of primary importance in population biology. The first theoretical approach to the problem dates back to the 1950s with the Kierstead, Slobodkin, and Skellam (KiSS) model, namely a continuous reaction-diffusion equation for a population growing on a patch of finite size L surrounded by a deadly environment with infinite mortality, i.e., an oasis in a desert. The main outcome of the model is that only patches above a critical size allow for population persistence. Here we introduce an individual-based analog of the KiSS model to investigate the effects of discreteness and demographic stochasticity. In particular, we study the average time to extinction both above and below the critical patch size of the continuous model and investigate the quasistationary distribution of the number of individuals for patch sizes above the critical threshold. PMID- 26274218 TI - Catch-slip bonds can be dispensable for motor force regulation during skeletal muscle contraction. AB - It is intriguing how multiple molecular motors can perform coordinated and synchronous functions, which is essential in various cellular processes. Recent studies on skeletal muscle might have shed light on this issue, where rather precise motor force regulation was partly attributed to the specific stochastic features of a single attached myosin motor. Though attached motors can randomly detach from actin filaments either through an adenosine triphosphate (ATP) hydrolysis cycle or through "catch-slip bond" breaking, their respective contribution in motor force regulation has not been clarified. Here, through simulating a mechanical model of sarcomere with a coupled Monte Carlo method and finite element method, we find that the stochastic features of an ATP hydrolysis cycle can be sufficient while those of catch-slip bonds can be dispensable for motor force regulation. PMID- 26274219 TI - Structural self-assembly and avalanchelike dynamics in locally adaptive networks. AB - Transport networks play a key role across four realms of eukaryotic life: slime molds, fungi, plants, and animals. In addition to the developmental algorithms that build them, many also employ adaptive strategies to respond to stimuli, damage, and other environmental changes. We model these adapting network architectures using a generic dynamical system on weighted graphs and find in simulation that these networks ultimately develop a hierarchical organization of the final weighted architecture accompanied by the formation of a system-spanning backbone. In addition, we find that the long term equilibration dynamics exhibit behavior reminiscent of glassy systems characterized by long periods of slow changes punctuated by bursts of reorganization events. PMID- 26274220 TI - Complex networks from space-filling bearings. AB - Two-dimensional space-filling bearings are dense packings of disks that can rotate without slip. We consider the entire first family of bearings for loops of four disks and propose a hierarchical construction of their contact network. We provide analytic expressions for the clustering coefficient and degree distribution, revealing bipartite scale-free behavior with a tunable degree exponent depending on the bearing parameters. We also analyze their average shortest path and percolation properties. PMID- 26274221 TI - Nonlinear q-voter model with inflexible zealots. AB - We study the dynamics of the nonlinear q-voter model with inflexible zealots in a finite well-mixed population. In this system, each individual supports one of two parties and is either a susceptible voter or an inflexible zealot. At each time step, a susceptible adopts the opinion of a neighbor if this belongs to a group of q>=2 neighbors all in the same state, whereas inflexible zealots never change their opinion. In the presence of zealots of both parties, the model is characterized by a fluctuating stationary state and, below a zealotry density threshold, the distribution of opinions is bimodal. After a characteristic time, most susceptibles become supporters of the party having more zealots and the opinion distribution is asymmetric. When the number of zealots of both parties is the same, the opinion distribution is symmetric and, in the long run, susceptibles endlessly swing from the state where they all support one party to the opposite state. Above the zealotry density threshold, when there is an unequal number of zealots of each type, the probability distribution is single peaked and non-Gaussian. These properties are investigated analytically and with stochastic simulations. We also study the mean time to reach a consensus when zealots support only one party. PMID- 26274222 TI - Shadows of the susceptible-infectious-susceptible immortality transition in small networks. AB - Much of the research on the behavior of the SIS model on networks has concerned the infinite size limit; in particular the phase transition between a state where outbreaks can reach a finite fraction of the population, and a state where only a finite number would be infected. For finite networks, there is also a dynamic transition-the immortality transition-when the per-contact transmission probability lambda reaches 1. If lambda<1, the probability that an outbreak will survive by an observation time t tends to zero as t->infinity; if lambda=1, this probability is 1. We show that treating lambda=1 as a critical point predicts the lambda dependence of the survival probability also for more moderate lambda values. The exponent, however, depends on the underlying network. This fact could, by measuring how a vertex's deletion changes the exponent, be used to evaluate the role of a vertex in the outbreak. Our work also confirms an extremely clear separation between the early die-off (from the outbreak failing to take hold in the population) and the later extinctions (corresponding to rare stochastic events of several consecutive transmission events failing to occur). PMID- 26274223 TI - Benchmark model to assess community structure in evolving networks. AB - Detecting the time evolution of the community structure of networks is crucial to identify major changes in the internal organization of many complex systems, which may undergo important endogenous or exogenous events. This analysis can be done in two ways: considering each snapshot as an independent community detection problem or taking into account the whole evolution of the network. In the first case, one can apply static methods on the temporal snapshots, which correspond to configurations of the system in short time windows, and match afterward the communities across layers. Alternatively, one can develop dedicated dynamic procedures so that multiple snapshots are simultaneously taken into account while detecting communities, which allows us to keep memory of the flow. To check how well a method of any kind could capture the evolution of communities, suitable benchmarks are needed. Here we propose a model for generating simple dynamic benchmark graphs, based on stochastic block models. In them, the time evolution consists of a periodic oscillation of the system's structure between configurations with built-in community structure. We also propose the extension of quality comparison indices to the dynamic scenario. PMID- 26274224 TI - Influence of Luddism on innovation diffusion. AB - We generalize the classical Bass model of innovation diffusion to include a new class of agents-Luddites-that oppose the spread of innovation. Our model also incorporates ignorants, susceptibles, and adopters. When an ignorant and a susceptible meet, the former is converted to a susceptible at a given rate, while a susceptible spontaneously adopts the innovation at a constant rate. In response to the rate of adoption, an ignorant may become a Luddite and permanently reject the innovation. Instead of reaching complete adoption, the final state generally consists of a population of Luddites, ignorants, and adopters. The evolution of this system is investigated analytically and by stochastic simulations. We determine the stationary distribution of adopters, the time needed to reach the final state, and the influence of the network topology on the innovation spread. Our model exhibits an important dichotomy: When the rate of adoption is low, an innovation spreads slowly but widely; in contrast, when the adoption rate is high, the innovation spreads rapidly but the extent of the adoption is severely limited by Luddites. PMID- 26274225 TI - Analytical expression for the exit probability of the q-voter model in one dimension. AB - We present in this paper an approximation that is able to give an analytical expression for the exit probability of the q-voter model in one dimension. This expression gives a better fit for the more recent data about simulations in large networks [A. M. Timpanaro and C. P. C. do Prado, Phys. Rev. E 89, 052808 (2014)] and as such departs from the expression rho(q)/rho(q)+(1-rho)(q) found in papers that investigated small networks only [R. Lambiotte and S. Redner, Europhys. Lett. 82, 18007 (2008); P. Przybyla et al., Phys. Rev. E 84, 031117 (2011); F. Slanina et al., Europhys. Lett. 82, 18006 (2008)]. The approximation consists in assuming a large separation on the time scales at which active groups of agents convince inactive ones and the time taken in the competition between active groups. Some interesting findings are that for q=2 we still have rho(2)/rho(2)+(1 rho)(2) as the exit probability and for q>2 we can obtain a lower-order approximation of the form rho(s)/rho(s)+(1-rho)(s) with s varying from q for low values of q to q-1/2 for large values of q. As such, this work can also be seen as a deduction for why the exit probability rho(q)/rho(q)+(1-rho)(q) gives a good fit, without relying on mean-field arguments or on the assumption that only the first step is nondeterministic, as q and q-1/2 will give very similar results when q->infinity. PMID- 26274226 TI - Magnetic-resonance pore imaging of nonsymmetric microscopic pore shapes. AB - Imaging of the microstructure of porous media such as biological tissue or porous solids is of high interest in health science and technology, engineering and material science. Magnetic resonance pore imaging (MRPI) is a recent technique based on nuclear magnetic resonance (NMR) which allows us to acquire images of the average pore shape in a given sample. Here we provide details on the experimental design, challenges, and requirements of MRPI, including its calibration procedures. Utilizing a laser-machined phantom sample, we present images of microscopic pores with a hemiequilateral triangular shape even in the presence of NMR relaxation effects at the pore walls. We therefore show that MRPI is applicable to porous samples without a priori knowledge about their pore shape and symmetry. Furthermore, we introduce "MRPI mapping," which combines MRPI with conventional magnetic resonance imaging (MRI). This enables one to resolve microscopic pore sizes and shapes spatially, thus expanding the application of MRPI to samples with heterogeneous distributions of pores. PMID- 26274227 TI - Phenotypic constraints promote latent versatility and carbon efficiency in metabolic networks. AB - System-level properties of metabolic networks may be the direct product of natural selection or arise as a by-product of selection on other properties. Here we study the effect of direct selective pressure for growth or viability in particular environments on two properties of metabolic networks: latent versatility to function in additional environments and carbon usage efficiency. Using a Markov chain Monte Carlo (MCMC) sampling based on flux balance analysis (FBA), we sample from a known biochemical universe random viable metabolic networks that differ in the number of directly constrained environments. We find that the latent versatility of sampled metabolic networks increases with the number of directly constrained environments and with the size of the networks. We then show that the average carbon wastage of sampled metabolic networks across the constrained environments decreases with the number of directly constrained environments and with the size of the networks. Our work expands the growing body of evidence about nonadaptive origins of key functional properties of biological networks. PMID- 26274228 TI - Selective pinning control of the average disease transmissibility in an HIV contact network. AB - Medication is applied to the HIV-infected nodes of high-risk contact networks with the aim of controlling the spread of disease to a predetermined maximum level. This intervention, known as pinning control, is performed both selectively and randomly in the network. These strategies are applied to 300 independent realizations per reference level of incidence on connected undirectional networks without isolated components and varying in size from 100 to 10,000 nodes per network. It is shown that a selective on-off pinning control strategy can control the networks studied with limited steady-state error and, comparing the medians of the doses from both strategies, uses 51.3% less medication than random pinning of all infected nodes. Selective pinning could possibly be used by public health specialists to identify the maximum level of HIV incidence in a population that can be achieved in a constrained funding environment. PMID- 26274229 TI - Hybrid recommendation methods in complex networks. AB - We propose two recommendation methods, based on the appropriate normalization of already existing similarity measures, and on the convex combination of the recommendation scores derived from similarity between users and between objects. We validate the proposed measures on three data sets, and we compare the performance of our methods to other recommendation systems recently proposed in the literature. We show that the proposed similarity measures allow us to attain an improvement of performances of up to 20% with respect to existing nonparametric methods, and that the accuracy of a recommendation can vary widely from one specific bipartite network to another, which suggests that a careful choice of the most suitable method is highly relevant for an effective recommendation on a given system. Finally, we study how an increasing presence of random links in the network affects the recommendation scores, finding that one of the two recommendation algorithms introduced here can systematically outperform the others in noisy data sets. PMID- 26274230 TI - Explosive synchronization with asymmetric frequency distribution. AB - In this work, we study the synchronization in a generalized Kuramoto model with frequency-weighted coupling. In particular, we focus on the situations in which the frequency distributions of oscillators are asymmetric. For typical unimodal frequency distributions, such as Lorentzian, Gaussian, triangle, and even special Rayleigh, we find that the synchronization transition in the model generally converts from the first order to the second order as the central frequency shifts toward positive direction. We characterize two interesting coherent states in the system: In the former, two phase-locking clusters are formed, rotating with the same frequency. They correspond to those oscillators with relatively high frequencies while the oscillators with relatively small frequencies are not entrained. In the latter, two phase-locking clusters rotate with different frequencies, leading to the oscillation of the order parameter. We further conduct theoretical analysis to reveal the relation between the asymmetric frequency distribution and the conversion of synchronization type, and justify the coherent states observed in the system. PMID- 26274231 TI - Payoff components and their effects in a spatial three-strategy evolutionary social dilemma. AB - We study a three-strategy spatial evolutionary prisoner's dilemma game with imitation and logit update rules. Players can follow the always-cooperating, always-defecting or the win-stay-lose-shift (WSLS) strategies and gain their payoff from games with their direct neighbors on a square lattice. The friendliness parameter of the WSLS strategy-characterizing its cooperation probability in the first round-tunes the cyclic component of the game determining whether the game can be characterized by a potential. We measured and calculated the phase diagrams of the system for a wide range of parameters. When the game is a potential game and the logit rule is applied, the theoretically predicted phase diagram agrees very well with the simulation results. Surprisingly, this phase diagram can be accurate even in the nonpotential case if there are only two surviving strategies in the stationary state; this result harmonizes with the fact that all 2*2 games are potential games. For the imitation dynamics, we found that the effects of spatiality combined with the presence of two cooperative strategies are so strong that they suppress even substantial changes in the payoff matrix, thus the phase diagrams are independent of the cyclic component's intensity. At the same time, this type of strategy update mechanism supports the formation of cooperative clusters that results in a cooperative society in a wider parameter range compared to the logit dynamics. PMID- 26274232 TI - Robustness of scale-free networks to cascading failures induced by fluctuating loads. AB - Taking into account the fact that overload failures in real-world functional networks are usually caused by extreme values of temporally fluctuating loads that exceed the allowable range, we study the robustness of scale-free networks against cascading overload failures induced by fluctuating loads. In our model, loads are described by random walkers moving on a network and a node fails when the number of walkers on the node is beyond the node capacity. Our results obtained by using the generating function method show that scale-free networks are more robust against cascading overload failures than Erdos-Renyi random graphs with homogeneous degree distributions. This conclusion is contrary to that predicted by previous works, which neglect the effect of fluctuations of loads. PMID- 26274233 TI - Econophysics of adaptive power markets: When a market does not dampen fluctuations but amplifies them. AB - The average economic agent is often used to model the dynamics of simple markets, based on the assumption that the dynamics of a system of many agents can be averaged over in time and space. A popular idea that is based on this seemingly intuitive notion is to dampen electric power fluctuations from fluctuating sources (as, e.g., wind or solar) via a market mechanism, namely by variable power prices that adapt demand to supply. The standard model of an average economic agent predicts that fluctuations are reduced by such an adaptive pricing mechanism. However, the underlying assumption that the actions of all agents average out on the time axis is not always true in a market of many agents. We numerically study an econophysics agent model of an adaptive power market that does not assume averaging a priori. We find that when agents are exposed to source noise via correlated price fluctuations (as adaptive pricing schemes suggest), the market may amplify those fluctuations. In particular, small price changes may translate to large load fluctuations through catastrophic consumer synchronization. As a result, an adaptive power market may cause the opposite effect than intended: Power demand fluctuations are not dampened but amplified instead. PMID- 26274234 TI - Internal-external stimulus competition in a system of interacting moving particles: Persuasion versus propaganda. AB - We propose a general nonlinear analytical framework to study the effect of an external stimulus in the internal state of a population of moving particles. This novel scheme allows us to study a broad range of excitation transport phenomena. In particular, considering social systems, it gives insight of the spatial dynamics influence in the competition between propaganda (mass media) and convincement. By extending the framework presented by Terranova et al. [Europhys. Lett. 105, 30007 (2014)], we now allow changes in individual's opinions due to a reflection induced by mass media. The equations of the model could be solved numerically, and, for some special cases, it is possible to derive analytical solutions for the steady states. We implement computational simulations for different social and dynamical systems to check the accuracy of our scheme and to study a broader variety of scenarios. In particular, we compare the numerical outcome with the analytical results for two possible real cases, finding a good agreement. From the results, we observe that mass media dominates the opinion state in slow dynamics communities; whereas, for higher agent active speeds, the rate of interactions increases and the opinion state is determined by a competition between propaganda and persuasion. This difference suggests that kinetics can not be neglected in the study of transport of any excitation over a particle system. PMID- 26274235 TI - Memory and burstiness in dynamic networks. AB - A discrete-time random process is described, which can generate bursty sequences of events. A Bernoulli process, where the probability of an event occurring at time t is given by a fixed probability x, is modified to include a memory effect where the event probability is increased proportionally to the number of events that occurred within a given amount of time preceding t. For small values of x the interevent time distribution follows a power law with exponent -2-x. We consider a dynamic network where each node forms, and breaks connections according to this process. The value of x for each node depends on the fitness distribution, rho(x), from which it is drawn; we find exact solutions for the expectation of the degree distribution for a variety of possible fitness distributions, and for both cases where the memory effect either is, or is not present. This work can potentially lead to methods to uncover hidden fitness distributions from fast changing, temporal network data, such as online social communications and fMRI scans. PMID- 26274236 TI - Most probable paths in temporal weighted networks: An application to ocean transport. AB - We consider paths in weighted and directed temporal networks, introducing tools to compute sets of paths of high probability. We quantify the relative importance of the most probable path between two nodes with respect to the whole set of paths and to a subset of highly probable paths that incorporate most of the connection probability. These concepts are used to provide alternative definitions of betweenness centrality. We apply our formalism to a transport network describing surface flow in the Mediterranean sea. Despite the full transport dynamics is described by a very large number of paths we find that, for realistic time scales, only a very small subset of high probability paths (or even a single most probable one) is enough to characterize global connectivity properties of the network. PMID- 26274237 TI - Competition and cooperation among different punishing strategies in the spatial public goods game. AB - Inspired by the fact that people have diverse propensities to punish wrongdoers, we study a spatial public goods game with defectors and different types of punishing cooperators. During the game, cooperators punish defectors with class specific probabilities and subsequently share the associated costs of sanctioning. We show that in the presence of different punishing cooperators the highest level of public cooperation is always attainable through a selection mechanism. Interestingly, the selection does not necessarily favor the evolution of punishers who would be able to prevail on their own against the defectors, nor does it always hinder the evolution of punishers who would be unable to prevail on their own. Instead, the evolutionary success of punishing strategies depends sensitively on their invasion velocities, which in turn reveals fascinating examples of both competition and cooperation among them. Furthermore, we show that under favorable conditions, when punishment is not strictly necessary for the maintenance of public cooperation, the less aggressive, mild form of sanctioning is the sole victor of the selection process. Our work reveals that natural strategy selection cannot only promote, but sometimes also hinders competition among prosocial strategies. PMID- 26274238 TI - Dynamics of social contagions with memory of nonredundant information. AB - A key ingredient in social contagion dynamics is reinforcement, as adopting a certain social behavior requires verification of its credibility and legitimacy. Memory of nonredundant information plays an important role in reinforcement, which so far has eluded theoretical analysis. We first propose a general social contagion model with reinforcement derived from nonredundant information memory. Then, we develop a unified edge-based compartmental theory to analyze this model, and a remarkable agreement with numerics is obtained on some specific models. We use a spreading threshold model as a specific example to understand the memory effect, in which each individual adopts a social behavior only when the cumulative pieces of information that the individual received from his or her neighbors exceeds an adoption threshold. Through analysis and numerical simulations, we find that the memory characteristic markedly affects the dynamics as quantified by the final adoption size. Strikingly, we uncover a transition phenomenon in which the dependence of the final adoption size on some key parameters, such as the transmission probability, can change from being discontinuous to being continuous. The transition can be triggered by proper parameters and structural perturbations to the system, such as decreasing individuals' adoption threshold, increasing initial seed size, or enhancing the network heterogeneity. PMID- 26274239 TI - Drastic disorder-induced reduction of signal amplification in scale-free networks. AB - Understanding information transmission across a network is a fundamental task for controlling and manipulating both biological and manmade information-processing systems. Here we show how topological resonant-like amplification effects in scale-free networks of signaling devices are drastically reduced when phase disorder in the external signals is considered. This is demonstrated theoretically by means of a starlike network of overdamped bistable systems, and confirmed numerically by simulations of scale-free networks of such systems. The taming effect of the phase disorder is found to be sensitive to the amplification's strength, while the topology-induced amplification mechanism is robust against this kind of quenched disorder in the sense that it does not significantly change the values of the coupling strength where amplification is maximum in its absence. PMID- 26274240 TI - Functional scale-free networks in the two-dimensional Abelian sandpile model. AB - Recently, the similarity of the functional network of the brain and the Ising model was investigated by Chialvo [Nat. Phys. 6, 744 (2010)]. This similarity supports the idea that the brain is a self-organized critical system. In this study we derive a functional network of the two-dimensional Bak-Tang-Wiesenfeld sandpile model as a self-organized critical model, and compare its characteristics with those of the functional network of the brain, obtained from functional magnetic resonance imaging. PMID- 26274241 TI - Soliton trapping in a disordered lattice. AB - In recent years, the competition between randomness and nonlinearity was extensively explored. In the present paper, the dynamics of solitons of the Ablowitz-Ladik model in the presence of a random potential is studied. In the absence of the random potential, it is an integrable model and the solitons are stable. As a result of the random potential, this stability is destroyed. In a certain regime, for short times, particlelike dynamics with constant mass is found; in another regime, particlelike dynamics with varying mass takes place. In particular, an effective potential is found that predicts correctly changes in the direction of motion of the soliton. This potential is a scaling function of time and strength of the potential, leading to a relation between the first time when the soliton changes direction and the strength of the random potential. PMID- 26274242 TI - Pattern phase diagram for two-dimensional arrays of coupled limit-cycle oscillators. AB - Arrays of coupled limit-cycle oscillators represent a paradigmatic example for studying synchronization and pattern formation. We find that the full dynamical equations for the phase dynamics of a limit-cycle oscillator array go beyond previously studied Kuramoto-type equations. We analyze the evolution of the phase field in a two-dimensional array and obtain a "phase diagram" for the resulting stationary and nonstationary patterns. Our results are of direct relevance in the context of currently emerging experiments on nano- and optomechanical oscillator arrays, as well as for any array of coupled limit-cycle oscillators that have undergone a Hopf bifurcation. The possible observation in optomechanical arrays is discussed briefly. PMID- 26274243 TI - Feedback as a mechanism for the resurrection of oscillations from death states. AB - The quenching of oscillations in interacting systems leads to several unwanted situations, which necessitate a suitable remedy to overcome the quenching. In this connection, this work addresses a mechanism that can resurrect oscillations in a typical situation. Through both numerical and analytical studies, we show that the candidate which is capable of resurrecting oscillations is nothing but the feedback, the one which is profoundly used in dynamical control and in biotherapies. Even in the case of a rather general system, we demonstrate analytically the applicability of the technique over one of the oscillation quenched states called amplitude death states. We also discuss some of the features of this mechanism such as adaptability of the technique with the feedback of only a few of the oscillators. PMID- 26274244 TI - Explosive synchronization is discontinuous. AB - Spontaneous explosive is an abrupt transition to collective behavior taking place in heterogeneous networks when the frequencies of the nodes are positively correlated with the node degree. This explosive transition was conjectured to be discontinuous. Indeed, numerical investigations reveal a hysteresis behavior associated with the transition. Here, we analyze explosive synchronization in star graphs. We show that in the thermodynamic limit the transition to (and out of) collective behavior is indeed discontinuous. The discontinuous nature of the transition is related to the nonlinear behavior of the order parameter, which in the thermodynamic limit exhibits multiple fixed points. Moreover, we unravel the hysteresis behavior in terms of the graph parameters. Our numerical results show that finite-size graphs are well described by our predictions. PMID- 26274245 TI - Global ballistic acceleration in a bouncing-ball model. AB - The ballistic increase for the velocity of a particle in a bouncing-ball model was investigated. The phenomenon is caused by accelerating structures in phase space known as accelerator modes. They lead to a regular and monotonic increase of the velocity. Here, both regular and ballistic Fermi acceleration coexist in the dynamics, leading the dynamics to two different growth regimes. We characterized deaccelerator modes in the dynamics, corresponding to unstable points in the antisymmetric position of the accelerator modes. In control parameter space, parameter sets for which these accelerations and deaccelerations constitute structures were obtained analytically. Since the mapping is not symplectic, we found fractal basins of influence for acceleration and deacceleration bounded by the stable and unstable manifolds, where the basins affect globally the average velocity of the system. PMID- 26274246 TI - Intercommunity resonances in multifrequency ensembles of coupled oscillators. AB - We generalize the Kuramoto model of globally coupled oscillators to multifrequency communities. A situation when mean frequencies of two subpopulations are close to the resonance 2:1 is considered in detail. We construct uniformly rotating solutions describing synchronization inside communities and between them. Remarkably, cross coupling across the frequencies can promote synchrony even when ensembles are separately asynchronous. We also show that the transition to synchrony due to the cross coupling is accompanied by a huge multiplicity of distinct synchronous solutions, which is directly related to a multibranch entrainment. On the other hand, for synchronous populations, the cross-frequency coupling can destroy phase locking and lead to chaos of mean fields. PMID- 26274247 TI - Nonlinear normal mode interactions in the SF(6) molecule studied with the aid of density functional theory. AB - Some exact interactions between vibrational modes in systems with discrete symmetry can be described by the theory of the bushes of nonlinear normal modes (NNMs) [G. M. Chechin and V. P. Sakhnenko, Phys. D (Amsterdam, Neth.) 117, 43 (1998)]. Each bush represents a dynamical object conserving the energy of the initial excitation. The existence of bushes of NNMs is ensured by some group theoretical selection rules. In G. M. Chechin et al. [Int. J. Nonlinear Mech. 38, 1451 (2003)], existence and stability of the bushes of vibrational modes in the simple octahedral model of mass points interacting via Lennard-Jones potential were investigated. In the present paper, we study these dynamical objects by the density functional theory in the SF(6) molecule, which possesses the same symmetry and structure. We have fully confirmed the results previously obtained in the framework of the group-theoretical approach and have found some properties of the bushes of NNMs. PMID- 26274248 TI - Perturbations and dynamics of reaction-diffusion systems with mass conservation. AB - In some reaction-diffusion systems where the total mass of their components is conserved, solutions with initial values near a homogeneous equilibrium converge to a simple localized pattern (spike) after exhibiting Turing-like patterns near the equilibrium for appropriate diffusion coefficients. In this study, we investigate the perturbed reaction-diffusion systems of such conserved systems. We show that a reaction-diffusion model with a globally stable homogeneous equilibrium can exhibit large amplitude Turing-like patterns in the transient dynamics. Moreover, we propose a three-component model, which exhibits an alternating repetition of spatially (almost) homogeneous oscillations and large amplitude Turing-like patterns. PMID- 26274249 TI - Wave-turbulence description of interacting particles: Klein-Gordon model with a Mexican-hat potential. AB - In field theory, particles are waves or excitations that propagate on the fundamental state. In experiments or cosmological models, one typically wants to compute the out-of-equilibrium evolution of a given initial distribution of such waves. Wave turbulence deals with out-of-equilibrium ensembles of weakly nonlinear waves, and is therefore well suited to address this problem. As an example, we consider the complex Klein-Gordon equation with a Mexican-hat potential. This simple equation displays two kinds of excitations around the fundamental state: massive particles and massless Goldstone bosons. The former are waves with a nonzero frequency for vanishing wave number, whereas the latter obey an acoustic dispersion relation. Using wave-turbulence theory, we derive wave kinetic equations that govern the coupled evolution of the spectra of massive and massless waves. We first consider the thermodynamic solutions to these equations and study the wave condensation transition, which is the classical equivalent of Bose-Einstein condensation. We then focus on nonlocal interactions in wave-number space: we study the decay of an ensemble of massive particles into massless ones. Under rather general conditions, these massless particles accumulate at low wave number. We study the dynamics of waves coexisting with such a strong condensate, and we compute rigorously a nonlocal Kolmogorov-Zakharov solution, where particles are transferred nonlocally to the condensate, while energy cascades towards large wave numbers through local interactions. This nonlocal cascading state constitutes the intermediate asymptotics between the initial distribution of waves and the thermodynamic state reached in the long-time limit. PMID- 26274250 TI - Phase reduction of a limit cycle oscillator perturbed by a strong amplitude modulated high-frequency force. AB - The phase reduction method for a limit cycle oscillator subjected to a strong amplitude-modulated high-frequency force is developed. An equation for the phase dynamics is derived by introducing a new, effective phase response curve. We show that if the effective phase response curve is everywhere positive (negative), then an entrainment of the oscillator to an envelope frequency is possible only when this frequency is higher (lower) than the natural frequency of the oscillator. Also, by using the Pontryagin maximum principle, we have derived an optimal waveform of the perturbation that ensures an entrainment of the oscillator with minimal power. The theoretical results are demonstrated with the Stuart-Landau oscillator and model neurons. PMID- 26274251 TI - Fast-slow analysis for parametrically and externally excited systems with two slow rationally related excitation frequencies. AB - We present a general method for analyzing mixed-mode oscillations (MMOs) in parametrically and externally excited systems with two low excitation frequencies (PEESTLEFs) for the case of arbitrary m:n relation between the slow frequencies of excitations. The validity of the approach has been demonstrated using the equations of Duffing and van der Pol, separately. Our study shows that, by introducing a slow variable and finding the relation between the slow variable and the slow excitations, PEESTLEFs can be transformed into a fast-slow form with a single slow variable and therefore MMOs observed in PEESTLEFs can be understood by the classical machinery of fast subsystem analysis of the transformed fast slow system. PMID- 26274252 TI - Consistency between functional and structural networks of coupled nonlinear oscillators. AB - In data-based reconstruction of complex networks, dynamical information can be measured and exploited to generate a functional network, but is it a true representation of the actual (structural) network? That is, when do the functional and structural networks match and is a perfect matching possible? To address these questions, we use coupled nonlinear oscillator networks and investigate the transition in the synchronization dynamics to identify the conditions under which the functional and structural networks are best matched. We find that, as the coupling strength is increased in the weak-coupling regime, the consistency between the two networks first increases and then decreases, reaching maximum in an optimal coupling regime. Moreover, by changing the network structure, we find that both the optimal regime and the maximum consistency will be affected. In particular, the consistency for heterogeneous networks is generally weaker than that for homogeneous networks. Based on the stability of the functional network, we propose further an efficient method to identify the optimal coupling regime in realistic situations where the detailed information about the network structure, such as the network size and the number of edges, is not available. Two real-world examples are given: corticocortical network of cat brain and the Nepal power grid. Our results provide new insights not only into the fundamental interplay between network structure and dynamics but also into the development of methodologies to reconstruct complex networks from data. PMID- 26274253 TI - Lyapunov exponent corresponding to enslaved phase dynamics: Estimation from time series. AB - A method for the estimation of the Lyapunov exponent corresponding to enslaved phase dynamics from time series has been proposed. It is valid for both nonautonomous systems demonstrating periodic dynamics in the presence of noise and coupled chaotic oscillators and allows us to estimate precisely enough the value of this Lyapunov exponent in the supercritical region of the control parameters. The main results are illustrated with the help of the examples of the noised circle map, the nonautonomous Van der Pole oscillator in the presence of noise, and coupled chaotic Rossler systems. PMID- 26274254 TI - Effective intermittency and cross correlations in the standard map. AB - We define auto- and cross-correlation functions capable of capturing dynamical characteristics induced by local phase-space structures in a general dynamical system. These correlation functions are calculated in the standard map for a range of values of the nonlinearity parameter k. Using a model of noninteracting particles, each evolving according to the same standard map dynamics and located initially at specific phase-space regions, we show that for 0.6infinity limit is shown to correspond to Galerkin truncation of the Euler equation. Direct numerical simulations (DNS) of the model are performed with resolutions up to 2048(3) and Taylor-Green initial data. DNS performed at large beta demonstrate that this simple classical hydrodynamical model presents a self truncation behavior, similar to that previously observed for the Gross Pitaeveskii equation in Krstulovic and Brachet [Phys. Rev. Lett. 106, 115303 (2011)]. The self-truncation regime of the generalized model is shown to reproduce the behavior of the truncated Euler equation demonstrated in Cichowlas et al. [Phys. Rev. Lett. 95, 264502 (2005)]. The long-time growth of the self truncation wave number k(st) appears to be self-similar. Two related alpha-Voigt versions of the eddy-damped quasinormal Markovian model and the Leith model are introduced. These simplified theoretical models are shown to reasonably reproduce intermediate time DNS results. The values of the self-similar exponents of these models are found analytically. PMID- 26274283 TI - Smoothed particle hydrodynamics simulations of evaporation and explosive boiling of liquid drops in microgravity. AB - The rapid evaporation and explosive boiling of a van der Waals (vdW) liquid drop in microgravity is simulated numerically in two-space dimensions using the method of smoothed particle hydrodynamics. The numerical approach is fully adaptive and incorporates the effects of surface tension, latent heat, mass transfer across the interface, and liquid-vapor interface dynamics. Thermocapillary forces are modeled by coupling the hydrodynamics to a diffuse-interface description of the liquid-vapor interface. The models start from a nonequilibrium square-shaped liquid of varying density and temperature. For a fixed density, the drop temperature is increased gradually to predict the point separating normal boiling at subcritical heating from explosive boiling at the superheat limit for this vdW fluid. At subcritical heating, spontaneous evaporation produces stable drops floating in a vapor atmosphere, while at near-critical heating, a bubble is nucleated inside the drop, which then collapses upon itself, leaving a smaller equilibrated drop embedded in its own vapor. At the superheat limit, unstable bubble growth leads to either fragmentation or violent disruption of the liquid layer into small secondary drops, depending on the liquid density. At higher superheats, explosive boiling occurs for all densities. The experimentally observed wrinkling of the bubble surface driven by rapid evaporation followed by a Rayleigh-Taylor instability of the thin liquid layer and the linear growth of the bubble radius with time are reproduced by the simulations. The predicted superheat limit (T(s)~0.96) is close to the theoretically derived value of T(s)=1 at zero ambient pressure for this vdW fluid. PMID- 26274284 TI - Effect of plate permeability on nonlinear stability of the asymptotic suction boundary layer. AB - The nonlinear stability of the asymptotic suction boundary layer is studied numerically, searching for finite-amplitude solutions that bifurcate from the laminar flow state. By changing the boundary conditions for disturbances at the plate from the classical no-slip condition to more physically sound ones, the stability characteristics of the flow may change radically, both for the linearized as well as the nonlinear problem. The wall boundary condition takes into account the permeability K of the plate; for very low permeability, it is acceptable to impose the classical boundary condition (K=0). This leads to a Reynolds number of approximately Re(c)=54400 for the onset of linearly unstable waves, and close to Re(g)=3200 for the emergence of nonlinear solutions [F. A. Milinazzo and P. G. Saffman, J. Fluid Mech. 160, 281 (1985); J. H. M. Fransson, Ph.D. thesis, Royal Institute of Technology, KTH, Sweden, 2003]. However, for larger values of the plate's permeability, the lower limit for the existence of linear and nonlinear solutions shifts to significantly lower Reynolds numbers. For the largest permeability studied here, the limit values of the Reynolds numbers reduce down to Re(c)=796 and Re(g)=294. For all cases studied, the solutions bifurcate subcritically toward lower Re, and this leads to the conjecture that they may be involved in the very first stages of a transition scenario similar to the classical route of the Blasius boundary layer initiated by Tollmien-Schlichting (TS) waves. The stability of these nonlinear solutions is also investigated, showing a low-frequency main unstable mode whose growth rate decreases with increasing permeability and with the Reynolds number, following a power law Re(-rho), where the value of rho depends on the permeability coefficient K. The nonlinear dynamics of the flow in the vicinity of the computed finite-amplitude solutions is finally investigated by direct numerical simulations, providing a viable scenario for subcritical transition due to TS waves. PMID- 26274285 TI - Modal interactions between a large-wavelength inclined interface and small wavelength multimode perturbations in a Richtmyer-Meshkov instability. AB - The interaction of a small-wavelength multimodal perturbation with a large wavelength inclined interface perturbation is investigated for the reshocked Richtmyer-Meshkov instability using three-dimensional simulations. The ares code, developed at Lawrence Livermore National Laboratory, was used for these simulations and a detailed comparison of simulation results and experiments performed at the Georgia Tech Shock Tube facility is presented first for code validation. Simulation results are presented for four cases that vary in large wavelength perturbation amplitude and the presence of secondary small-wavelength multimode perturbations. Previously developed measures of mixing and turbulence quantities are presented that highlight the large variation in perturbation length scales created by the inclined interface and the multimode complex perturbation. Measures are developed for entrainment, and turbulence anisotropy that help to identify the effects of and competition between each perturbations type. It is shown through multiple measures that before reshock the flow processes a distinct memory of the initial conditions that is present in both large-scale-driven entrainment measures and small-scale-driven mixing measures. After reshock the flow develops to a turbulentlike state that retains a memory of high-amplitude but not low-amplitude large-wavelength perturbations. It is also shown that the high-amplitude large-wavelength perturbation is capable of producing small-scale mixing and turbulent features similar to the small wavelength multimode perturbations. PMID- 26274286 TI - Capillary flow enhancement in rectangular polymer microchannels with a deformable wall. AB - We report the capillary flow enhancement in rectangular polymer microchannels, when one of the channel walls is a deformable polymer membrane. We provide detailed insight into the physics of elastocapillary interaction between the capillary flow and elastic membrane, which leads to significant improvements in capillary flow performance. As liquid flows by capillary action in such channels, the deformable wall deflects inwards due to the Young-Laplace pressure drop across the liquid meniscus. This, in turn, decreases the radius of curvature of the meniscus and increases the driving capillary pressure. A theoretical model is proposed to predict the resultant increase in filling speed and rise height, respectively, in deformable horizontal and vertical microchannels having large aspect ratios. A non-dimensional parameter J, which represents the ratio of the capillary force to the mechanical restoring force, is identified to quantify the elastocapillary effects in terms of the improvement in filling speed (for J>0.238) and the condition for channel collapse (J>1). The theoretical predictions show good agreement with experimental data obtained using deformable rectangular poly(dimethylsiloxane) microchannels. Both model predictions and experimental data show that over 15% improvement in the Washburn coefficient in horizontal channels, and over 30% improvement in capillary rise height in vertical channels, are possible prior to channel collapse. The proposed technique of using deformable membranes as channel walls is a viable method for capillary flow enhancement in microfluidic devices. PMID- 26274287 TI - Lattice Boltzmann simulation of multicomponent noncontinuum diffusion in fractal porous structures. AB - A lattice Boltzmann method (LBM) of multicomponent diffusion is developed to examine multicomponent, noncontinuum mass diffusion in porous media. An additional collision interaction is proposed to mimic the Knudsen diffusion caused by the collision interaction between gas molecules and solid pore walls. Using the improved LBM model, the ternary mixtures diffusion is simulated in fractal porous structures which are reconstructed by the random midpoint displacement algorithm. The effects of fractal characteristics and Knudsen diffusion resistance on the multicomponent diffusion in porous structures are investigated and discussed. The results indicate that the smaller fractal dimension enhances the diffusion rate of gas mixtures in fractal porous structures. When the dimensionless Knudsen diffusion coefficient is less than 20, the presence of Knudsen diffusion resistance reduces the rate of mass diffusion in porous structures obviously, especially for the species with larger molecular weight. PMID- 26274288 TI - Saffman-Taylor-like instability in a narrow gap induced by dielectric barrier discharge. AB - This work is inspired by the expansion of the plasma bubble in a narrow gap reported by Chu and Lee [Phys. Rev. Lett. 107, 225001 (2011)]. We report the unstable phenomena of the plasma-liquid interface with different curvature in a Hele-Shaw cell. Dielectric barrier discharge is produced in the cell at atmospheric pressure which is partially filled with silicone oil. We show that the Saffman-Taylor-like instability is observed on the bubble-type, channel-type, and drop-type interfaces. The Schlieren observation of the plasma-drop interaction reveals that there is a vapor layer around the drop and the particle image velocimetry shows the liquid flow inside the drop. We propose that the thermal Marangoni effect induced by the plasma heating is responsible for the unstable phenomena of the plasma-liquid interaction. The fluctuation of the interface is shown consistently with the Saffman-Taylor instability modified by the temperature-dependent velocity and surface tension. PMID- 26274289 TI - Disassembly time of deuterium-cluster-fusion plasma irradiated by an intense laser pulse. AB - Energetic deuterium ions from large deuterium clusters (>10nm diameter) irradiated by an intense laser pulse (>10(16)W/cm(2)) produce DD fusion neutrons for a time interval determined by the geometry of the resulting fusion plasma. We present an analytical solution of this time interval, the plasma disassembly time, for deuterium plasmas that are cylindrical in shape. Assuming a symmetrically expanding deuterium plasma, we calculate the expected fusion neutron yield and compare with an independent calculation of the yield using the concept of a finite confinement time at a fixed plasma density. The calculated neutron yields agree quantitatively with the available experimental data. Our one dimensional simulations indicate that one could expect a tenfold increase in total neutron yield by magnetically confining a 10-keV deuterium fusion plasma for 10ns. PMID- 26274290 TI - Ab initio calculation of the ion feature in x-ray Thomson scattering. AB - The spectrum of x-ray Thomson scattering is proportional to the dynamic structure factor. An important contribution is the ion feature which describes elastic scattering of x rays off electrons. We apply an ab initio method for the calculation of the form factor of bound electrons, the slope of the screening cloud of free electrons, and the ion-ion structure factor in warm dense beryllium. With the presented method we can calculate the ion feature from first principles. These results will facilitate a better understanding of x-ray scattering in warm dense matter and an accurate measurement of ion temperatures which would allow determining nonequilibrium conditions, e.g., along shock propagation. PMID- 26274291 TI - Exchange corrections in a low-temperature plasma. AB - We have studied the exchange corrections to linear electrostatic wave propagation in a plasma using a quantum kinetic formalism. Specifically, we have considered the zero-temperature limit. In order to simplify the calculations we have focused on the long-wavelength limit, i.e., wavelengths much longer than the de Broglie wavelength. For the case of ion-acoustic waves we have calculated the exchange correction both to the damping rate and the real part of the frequency. For Langmuir waves the frequency shift due to exchange effects is found. Our results are compared with the frequency shifts deduced from commonly used exchange potentials which are computed from density-functional theory. PMID- 26274292 TI - Dual-frequency modes of the dust acoustic surface wave in a semibounded system. AB - Dual-frequency modes of the dust acoustic surface waves propagating at the interface between a nonmagnetized multicomponent Lorentzian dusty plasma and a vacuum are investigated, including nonthermal and positron effects. The dispersion relation is kinetically derived by employing the specular reflection boundary condition and the dielectric permittivity for dusty plasma containing positrons. We found that there exist two modes of the dust acoustic surface wave; high- and low-frequency modes. We observe that both H and L modes are enhanced by the increase of the pair annihilation rate. However, the effects of positron density are twofold depending on the ratio of annihilated positrons. The effects of nonthermal plasmas are also investigated on the H and L modes of dust acoustic surface waves. We found that the nonthermal plasmas reduce the frequencies of both H and L modes. PMID- 26274293 TI - Slowdown mechanisms of ultraintense laser propagation in critical density plasma. AB - We use one- and two-dimensional particle-in-cell simulations to demonstrate that the propagation of an ultraintense laser (I=10(19)W/cm(2)) in critical density plasma can be interfered with by a high density plasma wall region generated at the propagation front. When the electron flow speed of the wall region exceeds a certain relativistic threshold, the region behaves as an overdense plasma due to a decrease of the effective critical density. The region forms then very small overdense plasma islands. The islands impede the propagation intermittently and slow down the propagation speed significantly. PMID- 26274294 TI - Generalized hydrodynamics model for strongly coupled plasmas. AB - Beginning with the exact equations of the Bogoliubov-Born-Green-Kirkwood-Yvon hierarchy, we obtain the density, momentum, and stress tensor-moment equations. We close the moment equations with two closures, one that guarantees an equilibrium state given by density-functional theory and another that includes collisions in the relaxation of the stress tensor. The introduction of a density functional-theory closure ensures self-consistency in the equation-of-state properties of the plasma (ideal and excess pressure, electric fields, and correlations). The resulting generalized hydrodynamics thus includes all impacts of Coulomb coupling, viscous damping, and the high-frequency (viscoelastic) response. We compare our results with those of several known models, including generalized hydrodynamic theory and models obtained using the Singwi-Tosi-Land Sjolander approximation and the quasilocalized charge approximation. We find that the viscoelastic response, including both the high-frequency elastic generalization and viscous wave damping, is important for correctly describing ion-acoustic waves. We illustrate this result by considering three very different systems: ultracold plasmas, dusty plasmas, and dense plasmas. The new model is validated by comparing its results with those of the current autocorrelation function obtained from molecular-dynamics simulations of Yukawa plasmas, and the agreement is excellent. Generalizations of this model to mixtures and quantum systems should be straightforward. PMID- 26274295 TI - Stationary solutions for the nonlinear Schrodinger equation modeling three dimensional spherical Bose-Einstein condensates in general potentials. AB - Stationary solutions for the cubic nonlinear Schrodinger equation modeling Bose Einstein condensates (BECs) confined in three spatial dimensions by general forms of a potential are studied through a perturbation method and also numerically. Note that we study both repulsive and attractive BECs under similar frameworks in order to deduce the effects of the potentials in each case. After outlining the general framework, solutions for a collection of specific confining potentials of physical relevance to experiments on BECs are provided in order to demonstrate the approach. We make several observations regarding the influence of the particular potentials on the behavior of the BECs in these cases, comparing and contrasting the qualitative behavior of the attractive and repulsive BECs for potentials of various strengths and forms. Finally, we consider the nonperturbative where the potential or the amplitude of the solutions is large, obtaining various qualitative results. When the kinetic energy term is small (relative to the nonlinearity and the confining potential), we recover the expected Thomas-Fermi approximation for the stationary solutions. Naturally, this also occurs in the large mass limit. Through all of these results, we are able to understand the qualitative behavior of spherical three-dimensional BECs in weak, intermediate, or strong confining potentials. PMID- 26274296 TI - Pulse reflection and transmission due to impurities in a granular chain. AB - Reflection and transmission due to the incident wave in one-dimensional bead chains when there are impurities have been studied. The impurities can be any kind of material, any size, and their numbers are arbitrary. The dependence of the transmission and the reflection on the numbers and the material parameters of the impurities are given. The analytical results are given by using the inverse scattering method. Substantial reflection is observed if there is only one steel bead. However, the reflection is negligible if there are two steel beads. The reflection monotonously increases as the numbers of the steel beads increase. The reflection remains a constant when the numbers of the steel beads are so many that the length composed by the steel beads is larger than the width of the solitary wave. It can be used to detect the impurities in the beads' chain by measuring the reflection of a pulse. PMID- 26274297 TI - Vertical dipole above a dielectric or metallic half space: Energy-flow considerations. AB - The emission pattern from a classical dipole located above and oriented perpendicular to a metallic or dielectric half space is calculated for a dipole driven at constant amplitude. Emphasis is placed on the fields in the metal or dielectric. It is shown that the radial Poynting vector in the metal points inwards when the frequency of the dipole is below the surface plasmon resonance frequency. In this case, energy actually flows out of the interface at small radii and the power entering the metal can actually oscillate as a function of radius. The Joule heating in the metal is also calculated for a cylindrical volume in the metal. When the metal is replaced by a dielectric having permittivity less than that of the medium in which the dipole is immersed, it is found that energy flows out of the interface for sufficiently large radii, a result reminiscent of the Goos-Hanchen effect. PMID- 26274298 TI - Electromagnetic waves in a model with Chern-Simons potential. AB - We investigated the appearance of Chern-Simons terms in electrodynamics at the surface or interface of materials. The requirement of locality, gauge invariance, and renormalizability in this model is imposed. Scattering and reflection of electromagnetic waves in three different homogeneous layers of media is determined. Snell's law is preserved. However, the transmission and reflection coefficient depend on the strength of the Chern-Simons interaction (connected with Hall conductance), and parallel and perpendicular components are mixed. PMID- 26274299 TI - Lattice mechanics of origami tessellations. AB - Origami-based design holds promise for developing materials whose mechanical properties are tuned by crease patterns introduced to thin sheets. Although there have been heuristic developments in constructing patterns with desirable qualities, the bridge between origami and physics has yet to be fully developed. To truly consider origami structures as a class of materials, methods akin to solid mechanics need to be developed to understand their long-wavelength behavior. We introduce here a lattice theory for examining the mechanics of origami tessellations in terms of the topology of their crease pattern and the relationship between the folds at each vertex. This formulation provides a general method for associating mechanical properties with periodic folded structures and allows for a concrete connection between more conventional materials and the mechanical metamaterials constructed using origami-based design. PMID- 26274300 TI - Deep optical penetration dynamics in photobending. AB - We model both the photostationary state and dynamics of an illuminated, photosensitive, glassy liquid crystalline sheet. To illustrate the interplay between local tilt theta of the sheet, effective incident intensity, curvature, and dynamics, we adopt the simplest variation of local incident light intensity with angle, that is, costheta. The tilt in the stationary state never overshoots the vertical, but maximum curvature could be seen in the middle of the sheet for intense light. In dynamics, overshoot and self-eclipsing arise, revealing how important moving fronts of light penetration are. Eclipsing is qualitatively as in the experiments of Yu et al. [Y. Yu, M. Nakano, and T. Ikeda, Nature (London) 425, 145 (2003)]. PMID- 26274301 TI - Effect of angular momentum conservation on hydrodynamic simulations of colloids. AB - In contrast to most real fluids, angular momentum is not a locally conserved quantity in some mesoscopic simulation methods. Here we quantify the importance of this conservation in the flow fields associated with different colloidal systems. The flow field is analytically calculated with and without angular momentum conservation for the multiparticle collision dynamics (MPC) method, and simulations are performed to verify the predictions. The flow field generated around a colloidal particle moving under an external force with slip boundary conditions depends on the conservation of angular momentum, and the amplitude of the friction force is substantially affected. Interestingly, no dependence on the angular momentum conservation is found for the flow fields generated around colloids under the influence of phoretic forces. Moreover, circular Couette flow between a no-slip and a slip cylinder is investigated, which allows us to validate one of the two existing expressions for the MPC stress tensor. PMID- 26274302 TI - Stochastic determination of matrix determinants. AB - Matrix determinants play an important role in data analysis, in particular when Gaussian processes are involved. Due to currently exploding data volumes, linear operations-matrices-acting on the data are often not accessible directly but are only represented indirectly in form of a computer routine. Such a routine implements the transformation a data vector undergoes under matrix multiplication. While efficient probing routines to estimate a matrix's diagonal or trace, based solely on such computationally affordable matrix-vector multiplications, are well known and frequently used in signal inference, there is no stochastic estimate for its determinant. We introduce a probing method for the logarithm of a determinant of a linear operator. Our method rests upon a reformulation of the log-determinant by an integral representation and the transformation of the involved terms into stochastic expressions. This stochastic determinant determination enables large-size applications in Bayesian inference, in particular evidence calculations, model comparison, and posterior determination. PMID- 26274303 TI - Comparing Monte Carlo methods for finding ground states of Ising spin glasses: Population annealing, simulated annealing, and parallel tempering. AB - Population annealing is a Monte Carlo algorithm that marries features from simulated-annealing and parallel-tempering Monte Carlo. As such, it is ideal to overcome large energy barriers in the free-energy landscape while minimizing a Hamiltonian. Thus, population-annealing Monte Carlo can be used as a heuristic to solve combinatorial optimization problems. We illustrate the capabilities of population-annealing Monte Carlo by computing ground states of the three dimensional Ising spin glass with Gaussian disorder, while comparing to simulated annealing and parallel-tempering Monte Carlo. Our results suggest that population annealing Monte Carlo is significantly more efficient than simulated annealing but comparable to parallel-tempering Monte Carlo for finding spin-glass ground states. PMID- 26274304 TI - Combined deterministic-stochastic framework for modeling the agglomeration of colloidal particles. AB - We present a multiscale model, based on molecular dynamics (MD) and kinetic Monte Carlo (kMC), to study the aggregation driven growth of colloidal particles. Coarse-grained molecular dynamics (CGMD) simulations are employed to detect key agglomeration events and calculate the corresponding rate constants. The kMC simulations employ these rate constants in a stochastic framework to track the growth of the agglomerates over longer time scales and length scales. One of the hallmarks of the model is a unique methodology to detect and characterize agglomeration events. The model accounts for individual cluster-scale effects such as change in size due to aggregation as well as local molecular-scale effects such as changes in the number of neighbors of each molecule in a colloidal cluster. Such definition of agglomeration events allows us to grow the cluster to sizes that are inaccessible to molecular simulations as well as track the shape of the growing cluster. A well-studied system, comprising fullerenes in NaCl electrolyte solution, was simulated to validate the model. Under the simulated conditions, the agglomeration process evolves from a diffusion limited cluster aggregation (DLCA) regime to percolating cluster in transition and finally to a gelation regime. Overall the data from the multiscale numerical model shows good agreement with existing theory of colloidal particle growth. Although in the present study we validated our model by specifically simulating fullerene agglomeration in electrolyte solution, the model is versatile and can be applied to a wide range of colloidal systems. PMID- 26274305 TI - Differential porosimetry and permeametry for random porous media. AB - Accurate determination of geometrical and physical properties of natural porous materials is notoriously difficult. Continuum multiscale modeling has provided carefully calibrated realistic microstructure models of reservoir rocks with floating point accuracy. Previous measurements using synthetic microcomputed tomography (MU-CT) were based on extrapolation of resolution-dependent properties for discrete digitized approximations of the continuum microstructure. This paper reports continuum measurements of volume and specific surface with full floating point precision. It also corrects an incomplete description of rotations in earlier publications. More importantly, the methods of differential permeametry and differential porosimetry are introduced as precision tools. The continuum microstructure chosen to exemplify the methods is a homogeneous, carefully calibrated and characterized model for Fontainebleau sandstone. The sample has been publicly available since 2010 on the worldwide web as a benchmark for methodical studies of correlated random media. High-precision porosimetry gives the volume and internal surface area of the sample with floating point accuracy. Continuum results with floating point precision are compared to discrete approximations. Differential porosities and differential surface area densities allow geometrical fluctuations to be discriminated from discretization effects and numerical noise. Differential porosimetry and Fourier analysis reveal subtle periodic correlations. The findings uncover small oscillatory correlations with a period of roughly 850MUm, thus implying that the sample is not strictly stationary. The correlations are attributed to the deposition algorithm that was used to ensure the grain overlap constraint. Differential permeabilities are introduced and studied. Differential porosities and permeabilities provide scale dependent information on geometry fluctuations, thereby allowing quantitative error estimates. PMID- 26274306 TI - Lattice Boltzmann method for diffusion-limited partial dissolution of fluids. AB - A lattice Boltzmann model for two partially miscible fluids is developed. By partially miscible we mean that, although there is a definite interfacial region separating the two fluids with a surface tension force acting at all points of the transition region, each fluid can nonetheless accept molecules from the other fluid up to a set solubility limit. We allow each fluid to diffuse into the other with the solubility and diffusivity in each fluid being input parameters. The approach is to define two regions within the fluid: one interfacial region having finite width, across which most of the concentration change occurs, and in which a surface tension force and color separation step are allowed for and one miscible fluid region where the concentration of the binary fluids follows an advection-diffusion equation and the mixture as a whole obeys the Navier-Stokes incompressible flow equations. Numerical examples are presented in which the algorithm produces results that are quantitatively compared to exact analytical results as well as qualitatively examined for their reasonableness. The model has the ability to simulate how bubbles of one fluid flow through another while dissolving their contents as well as to simulate a range of practical invasion problems such as injecting supercritical CO(2) into a porous material saturated with water for sequestration purposes. PMID- 26274307 TI - Linearized lattice Boltzmann method for micro- and nanoscale flow and heat transfer. AB - Ability to characterize the heat transfer in flowing gases is important for a wide range of applications involving micro- and nanoscale devices. Gas flows away from the continuum limit can be captured using the Boltzmann equation, whose analytical solution poses a formidable challenge. An efficient and accurate numerical simulation of the Boltzmann equation is thus highly desirable. In this article, the linearized Boltzmann Bhatnagar-Gross-Krook equation is used to develop a hierarchy of thermal lattice Boltzmann (LB) models based on half-space Gaussian-Hermite (GH) quadrature ranging from low to high algebraic precision, using double distribution functions. Simplified versions of the LB models in the continuum limit are also derived, and are shown to be consistent with existing thermal LB models for noncontinuum heat transfer reported in the literature. Accuracy of the proposed LB hierarchy is assessed by simulating thermal Couette flows for a wide range of Knudsen numbers. Effects of the underlying quadrature schemes (half-space GH vs full-space GH) and continuum-limit simplifications on computational accuracy are also elaborated. The numerical findings in this article provide direct evidence of improved computational capability of the proposed LB models for modeling noncontinuum flows and heat transfer at small length scales. PMID- 26274308 TI - Calculation of a fluctuating entropic force by phase space sampling. AB - A polymer chain pinned in space exerts a fluctuating force on the pin point in thermal equilibrium. The average of such fluctuating force is well understood from statistical mechanics as an entropic force, but little is known about the underlying force distribution. Here, we introduce two phase space sampling methods that can produce the equilibrium distribution of instantaneous forces exerted by a terminally pinned polymer. In these methods, both the positions and momenta of mass points representing a freely jointed chain are perturbed in accordance with the spatial constraints and the Boltzmann distribution of total energy. The constraint force for each conformation and momentum is calculated using Lagrangian dynamics. Using terminally pinned chains in space and on a surface, we show that the force distribution is highly asymmetric with both tensile and compressive forces. Most importantly, the mean of the distribution, which is equal to the entropic force, is not the most probable force even for long chains. Our work provides insights into the mechanistic origin of entropic forces, and an efficient computational tool for unbiased sampling of the phase space of a constrained system. PMID- 26274309 TI - Modified phase-field-crystal model for solid-liquid phase transitions. AB - A modified phase-field-crystal (PFC) model is proposed to describe solid-liquid phase transitions by reconstructing the correlation function. The effects of fitting parameters of our modified PFC model on the bcc-liquid phase diagram, numerical stability, and solid-liquid interface properties during planar interface growth are examined carefully. The results indicate that the increase of the correlation function peak width at k=k(m) will enhance the stability of the ordered phase, while the increase of peak height at k=0 will narrow the two phase coexistence region. The third-order term in the free-energy function and the short wave-length of the correlation function have significant influences on the numerical stability of the PFC model. During planar interface growth, the increase of peak width at k=k(m) will decrease the interface width and the velocity coefficient C, but increase the anisotropy of C and the interface free energy. Finally, the feasibility of the modified phase-field-crystal model is demonstrated with a numerical example of three-dimensional dendritic growth of a body-centered-cubic structure. PMID- 26274310 TI - Monte Carlo algorithm for free energy calculation. AB - We propose a Monte Carlo algorithm for the free energy calculation based on configuration space sampling. An upward or downward temperature scan can be used to produce F(T). We implement this algorithm for the Ising model on a square lattice and triangular lattice. Comparison with the exact free energy shows an excellent agreement. We analyze the properties of this algorithm and compare it with the Wang-Landau algorithm, which samples in energy space. This method is applicable to general classical statistical models. The possibility of extending it to quantum systems is discussed. PMID- 26274311 TI - Comment on "Kinetic theory for a mobile impurity in a degenerate Tonks-Girardeau gas". AB - In a recent paper Gamayun et al. [O. Gamayun, O. Lychkovskiy, and V. Cheianov, Phys. Rev. E 90, 032132 (2014)] studied the dynamics of a mobile impurity weakly coupled to a one-dimensional Tonks-Girardeau gas of strongly interacting bosons. Employing the Boltzmann equation approach, they, in particular, arrived at the following conclusions: (i) a light impurity, being accelerated by a constant force F, does not exhibit Bloch oscillations, which were predicted and studied by Gangardt and co-workers [D. M. Gangardt and A. Kamenev, Phys. Rev. Lett. 102, 070402 (2009); M. Schecter, D. M. Gangardt, and A. Kamanev, Ann. Phys. (N.Y.) 327, 639 (2012)]; (ii) a heavy impurity does undergo Bloch oscillations, accompanied by a drift with the velocity v(D)??[F]. In this Comment we argue that result (i) is an artifact of the classical Boltzmann approximation. The latter misses the formation of the quasibound state between the impurity and a hole. Its dispersion relation E(b)(P,rho) is a smooth periodic function of momentum P with the period 2k(F)=2pihrho, where rho is a density of the host gas. Being accelerated by a small force, such a bound-state exhibits Bloch oscillations superimposed with the drift velocity v(D)=MUF. The mobility MU may be expressed exactly [M. Schecter et al., Ann. Phys. (N.Y.) 327, 639 (2012)] in terms of E(b)(P,rho). Result (ii), while not valid at exponentially small forces, indeed reflects an interesting intermediate-force behavior. PMID- 26274312 TI - Reply to "Comment on 'Kinetic theory for a mobile impurity in a degenerate Tonks Girardeau gas' ". AB - In our recent paper [O. Gamayun, O. Lychkovskiy, and V. Cheianov, Phys. Rev. E 90, 032132 (2014)] we studied the dynamics of a mobile impurity particle weakly interacting with the Tonks-Girardeau gas and pulled by a small external force F. Working in the regime when the thermodynamic limit is taken prior to the small force limit, we found that the Bloch oscillations of the impurity velocity are absent in the case of a light impurity. Further, we argued that for a light impurity the steady-state drift velocity V(D) remains finite in the limit F->0. These results are in contradiction with earlier works by Gangardt and co-workers [D. M. Gangardt and A. Kamenev, Phys. Rev. Lett. 102, 070402 (2009); M. Schecter, D. M. Gangardt, and A. Kamenev, Ann. Phys. (NY) 327, 639 (2012)]. One of us has conjectured [O. Lychkovskiy, Phys. Rev. A 91, 040101 (2015)] that the central assumption of these works, the adiabaticity of the dynamics, can break down in the thermodynamic limit. In the preceding Comment [M. Schecter, D. M. Gangardt, and A. Kamenev, Phys. Rev. E 92, 016101 (2015)], Schecter et al. have argued against this conjecture and in support of the existence of Bloch oscillations and the linearity of V(D)(F). They have suggested that the ground state of the impurity-fluid system is a quasibound state and that this is sufficient to ensure adiabaticity in the thermodynamic limit. Their analytical argument is based on a certain truncation of the Hilbert space of the system. We argue that extending the results and intuition based on their truncated model on the original many body problem lacks justification. PMID- 26274313 TI - Comment on "Third law of thermodynamics as a key test of generalized entropies". AB - Bento et al. [Phys. Rev. E 91, 022105 (2015)] state that the Tsallis entropy violates the third law of thermodynamics for q<=0 and 0=1, since there is no distribution maximizing the Tsallis entropy for the intervals q<=0 and 0=1, using arguments like there is no distribution maximizing the Tsallis entropy for the interval q<0 (in which the third law is not verified) compatible with the problem energy expression. In this Reply, we first (and most importantly) show that the Comment misses the point. In our original work we have considered the now already standard construction of the Tsallis statistics. So, if indeed such statistics lacks a maximization principle (a fact irrelevant in our protocol), this is an inherent feature of the statistics itself and not a problem with our analysis. Second, some arguments used by Bagci and Oikonomou (for 00.05). In conclusion, our experimental results provide evidence that the T allele of rs17168525 in the 3'-UTR of myotrophin might influence the level of myotrophin protein by interfering with let-7/miR-98 binding. PMID- 26274322 TI - Surveillance of Human Astrovirus Infection in Brazil: The First Report of MLB1 Astrovirus. AB - Human astrovirus (HAstV) represents the third most common virus associated with acute diarrhea (AD). This study aimed to estimate the prevalence of HAstV infection in Brazilian children under 5 years of age with AD, investigate the presence of recently described HAstV strains, through extensive laboratory-based surveillance of enteric viral agents in three Brazilian coastal regions between 2005 and 2011. Using reverse transcription-polymerase chain reaction (RT-PCR), the overall HAstV detection rate reached 7.1% (207/2.913) with percentage varying according to the geographic region: 3.9% (36/921) in the northeast, 7.9% in the south (71/903) and 9.2% in the southeast (100/1.089) (p < 0.001). HAstV were detected in cases of all age groups. Detection rates were slightly higher during the spring. Nucleotide sequence analysis of a 320-bp ORF2 fragment revealed that HAstV-1 was the predominant genotype throughout the seven years of the study. The novel AstV-MLB1 was detected in two children with AD from a subset of 200 samples tested, demonstrating the circulation of this virus both the in northeastern and southeastern regions of Brazil. These results provide additional epidemiological and molecular data on HAstV circulation in three Brazilian coastal regions, highlighting its potential to cause infantile AD. PMID- 26274323 TI - Systematic Mapping of Protein Mutational Space by Prolonged Drift Reveals the Deleterious Effects of Seemingly Neutral Mutations. AB - Systematic mappings of the effects of protein mutations are becoming increasingly popular. Unexpectedly, these experiments often find that proteins are tolerant to most amino acid substitutions, including substitutions in positions that are highly conserved in nature. To obtain a more realistic distribution of the effects of protein mutations, we applied a laboratory drift comprising 17 rounds of random mutagenesis and selection of M.HaeIII, a DNA methyltransferase. During this drift, multiple mutations gradually accumulated. Deep sequencing of the drifted gene ensembles allowed determination of the relative effects of all possible single nucleotide mutations. Despite being averaged across many different genetic backgrounds, about 67% of all nonsynonymous, missense mutations were evidently deleterious, and an additional 16% were likely to be deleterious. In the early generations, the frequency of most deleterious mutations remained high. However, by the 17th generation, their frequency was consistently reduced, and those remaining were accepted alongside compensatory mutations. The tolerance to mutations measured in this laboratory drift correlated with sequence exchanges seen in M.HaeIII's natural orthologs. The biophysical constraints dictating purging in nature and in this laboratory drift also seemed to overlap. Our experiment therefore provides an improved method for measuring the effects of protein mutations that more closely replicates the natural evolutionary forces, and thereby a more realistic view of the mutational space of proteins. PMID- 26274324 TI - Spatial and Temporal Control of Cavitation Allows High In Vitro Transfection Efficiency in the Absence of Transfection Reagents or Contrast Agents. AB - Sonoporation using low-frequency high-pressure ultrasound (US) is a non-viral approach for in vitro and in vivo gene delivery. In this study, we developed a new sonoporation device designed for spatial and temporal control of ultrasound cavitation. The regulation system incorporated in the device allowed a real-time control of the cavitation level during sonoporation. This device was evaluated for the in vitro transfection efficiency of a plasmid coding for Green Fluorescent Protein (pEGFP-C1) in adherent and non-adherent cell lines. The transfection efficiency of the device was compared to those observed with lipofection and nucleofection methods. In both adherent and non-adherent cell lines, the sonoporation device allowed high rate of transfection of pEGFP-C1 (40 80%), as determined by flow cytometry analysis of GFP expression, along with a low rate of mortality assessed by propidium iodide staining. The transfection efficiency and toxicity of sonoporation on the non-adherent cell lines Jurkat and K562 were similar to those of nucleofection, while these two cell lines were resistant to transfection by lipofection. Moreover, sonoporation was used to produce three stably transfected human lymphoma and leukemia lines. Significant transfection efficiency was also observed in two fresh samples of human acute myeloid leukemia cells. In conclusion, we developed a user-friendly and cost effective ultrasound device, well adapted for routine in vitro high-yield transfection experiments and which does not require the use of any transfection reagent or gas micro-bubbles. PMID- 26274325 TI - Evidence of Drought Stress Memory in the Facultative CAM, Aptenia cordifolia: Possible Role of Phytohormones. AB - Although plant responses to drought stress have been studied in detail in several plant species, including CAM plants, the occurrence of stress memory and possible mechanisms for its regulation are still very poorly understood. In an attempt to better understand the occurrence and possible mechanisms of regulation of stress memory in plants, we measured the concentrations of phytohormones in Aptenia cordifolia exposed to reiterated drought, together with various stress indicators, including leaf water contents, photosynthesis and mechanisms of photo and antioxidant protection. Results showed that plants exposed to drought stress responded differently if previously challenged with a first drought. Gibberellin levels decreased upon exposure to the first drought and remained lower in double stressed plants compared with those exposed to stress for the first time. In contrast, abscisic acid levels were higher in double- than single-stressed plants. This occurred in parallel with alterations in hydroperoxide levels, but not with malondialdehyde levels, thus suggesting an increased oxidation state that did not result in oxidative damage in double-stressed plants. It is concluded that (i) drought stress memory occurs in double-stressed A. cordifolia plants, (ii) both gibberellins and abscisic acid may play a role in plant response to repeated periods of drought, and (iii) changes in abscisic acid levels in double-stressed plants may have a positive effect by modulating changes in the cellular redox state with a role in signalling, rather than cause oxidative damage to the cell. PMID- 26274326 TI - Subcutaneous Construction of Engineered Adipose Tissue with Fat Lobule-Like Structure Using Injectable Poly-Benzyl-L-Glutamate Microspheres Loaded with Adipose-Derived Stem Cells. AB - Porous microcarriers were fabricated from synthesized poly(gamma-benzyl-L glutamate) (PBLG) polymer to engineer adipose tissue with lobule-like structure via the injectable approach. The adipogenic differentiation of human adipose derived stem cells (hASCs) seeded on porous PBLG microcarriers was determined by adipogenic gene expression and glycerol-3-phosphate dehydrogenase enzyme activity. In vitro adipogenic cultivation was performed for 7 days, and induced hASC/PBLG complex (Adi-ASC/PBLG group) was subcutaneously injected into nude mice. Injections of PBLG microcarriers alone (PBLG group) and non-induced hASC/PBLG complex (ASC/PBLG group) served as controls. Newly formed tissues were harvested after 4 and 8 weeks. Generation of subcutaneous adipose tissue with typical lobule-like structure separated by fibrous septa was observed upon injection of adipogenic-induced hASC/microsphere complex. Adipogenesis significantly increased in the Adi-ASC/PBLG group compared with the control groups. The angiogenesis in the engineered adipose tissue was comparable to that in normal tissue as determined by capillary density and luminal diameter. Cell tracking assay demonstrated that labeled hASCs remained detectable in the neo generated tissues 8 weeks post-injection using green fluorescence protein-labeled hASCs. These results indicate that adipose tissue with typical lobule-like structure could be engineered using injectable porous PBLG microspheres loaded with adipogenic-induced hASCs. PMID- 26274327 TI - Generalised Anxiety Disorder--A Twin Study of Genetic Architecture, Genome-Wide Association and Differential Gene Expression. AB - Generalised Anxiety Disorder (GAD) is a common anxiety-related diagnosis, affecting approximately 5% of the adult population. One characteristic of GAD is a high degree of anxiety sensitivity (AS), a personality trait which describes the fear of arousal-related sensations. Here we present a genome-wide association study of AS using a cohort of 730 MZ and DZ female twins. The GWAS showed a significant association for a variant within the RBFOX1 gene. A heritability analysis of the same cohort also confirmed a significant genetic component with h2 of 0.42. Additionally, a subset of the cohort (25 MZ twins discordant for AS) was studied for evidence of differential expression using RNA-seq data. Significant differential expression of two exons with the ITM2B gene within the discordant MZ subset was observed, a finding that was replicated in an independent cohort. While previous research has shown that anxiety has a high comorbidity with a variety of psychiatric and neurodegenerative disorders, our analysis suggests a novel etiology specific to AS. PMID- 26274328 TI - Ethnic Variations in Central Corneal Thickness in a Rural Population in China: The Yunnan Minority Eye Studies. AB - PURPOSE: To describe the ethnic differences in central corneal thickness (CCT) in population-based samples of ethnic Bai, Yi and Han people living in rural China. METHODS: 6504 adults (2119 ethnic Bai, 2202 ethnic Yi and 2183 ethnic Han) aged 50 years or older participated in the study. Each subject underwent standardized ocular examinations and interviewer-administered questionnaires for risk factor assessment. CCT was measured for both eyes using an ultrasound pachymeter. Regression and principal component analysis were performed to examine the relationship of ethnicity and other factors with CCT. RESULTS: The mean CCT readings were 536.4 +/- 34.2 MUm in ethnic Bai, 532.1 +/- 32.1 MUm in ethnic Yi and 529.6 +/- 32.7 MUm in ethnic Han adults (P<0.001), respectively. There was a decreasing trend of mean CCT with increasing age across all ethnic groups. In multivariate linear regression models, increasing CCT was associated with younger age (P<0.001), male gender (P<0.001), Bai (P<0.001) or Yi (P<0.001) ethnicity, greater body mass index (P<0.001), higher systolic blood pressure (P<0.001), greater corneal curvature (P<0.001), deeper anterior chamber (P < 0.001), and thicker lens (P<0.001). Ethnicity contributed significantly to presence of thin cornea (60%; P< 0.001) compared with other factors. CCT had similar impact on intraocular pressure readings across all ethnic groups. CONCLUSIONS: This study of more than 6500 multiethnic participants demonstrates significant ethnic variations in CCT, with Han ethnicity having the thinnest cornea compared with ethnic minorities. These data are essential to guide future multiethnic clinical trials on CCT-related ocular conditions such as glaucoma. PMID- 26274330 TI - Correction: Mechanism of Inhibition of the Human Sirtuin Enzyme SIRT3 by Nicotinamide: Computational and Experimental Studies. PMID- 26274329 TI - Targeted Next-Generation Sequencing for Clinical Diagnosis of 561 Mendelian Diseases. AB - BACKGROUND: Targeted next-generation sequencing (NGS) is a cost-effective approach for rapid and accurate detection of genetic mutations in patients with suspected genetic disorders, which can facilitate effective diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: We designed a capture array to mainly capture all the coding sequence (CDS) of 2,181 genes associated with 561 Mendelian diseases and conducted NGS to detect mutations. The accuracy of NGS was 99.95%, which was obtained by comparing the genotypes of selected loci between our method and SNP Array in four samples from normal human adults. We also tested the stability of the method using a sample from normal human adults. The results showed that an average of 97.79% and 96.72% of single-nucleotide variants (SNVs) in the sample could be detected stably in a batch and different batches respectively. In addition, the method could detect various types of mutations. Some disease causing mutations were detected in 69 clinical cases, including 62 SNVs, 14 insertions and deletions (Indels), 1 copy number variant (CNV), 1 microdeletion and 2 microduplications of chromosomes, of which 35 mutations were novel. Mutations were confirmed by Sanger sequencing or real-time polymerase chain reaction (PCR). CONCLUSIONS/SIGNIFICANCE: Results of the evaluation showed that targeted NGS enabled to detect disease-causing mutations with high accuracy, stability, speed and throughput. Thus, the technology can be used for the clinical diagnosis of 561 Mendelian diseases. PMID- 26274331 TI - LKB1 Is Required for the Development and Maintenance of Stereocilia in Inner Ear Hair Cells in Mice. AB - The LKB1 gene, which encodes a serine/threonine kinase, was discovered to play crucial roles in cell differentiation, proliferation, and the establishment of cell polarity. In our study, LKB1 conditional knockout mice (Atoh1-LKB1-/- mice) were generated to investigate LKB1 function in the inner ear. Tests of auditory brainstem response and distortion product otoacoustic emissions revealed significant decreases in the hearing sensitivities of the Atoh1-LKB1-/- mice. In Atoh1-LKB1-/- mice, malformations of hair cell stereocilliary bundles were present as early as postnatal day 1 (P1), a time long before the maturation of the hair cell bundles. In addition, we also observed outer hair cell (OHC) loss starting at P14. The impaired stereocilliary bundles occurred long before the presence of hair cell loss. Stereociliary cytoskeletal structure depends on the core actin-based cytoskeleton and several actin-binding proteins. By Western blot, we examined actin-binding proteins, specifically ERM (ezrin/radixin/moesin) proteins involved in the regulation of the actin cytoskeleton of hair cell stereocilia. Our results revealed that the phosphorylation of ERM proteins (pERM) was significantly decreased in mutant mice. Thus, we propose that the decreased pERM may be a key factor for the impaired stereocillia function, and the damaged stereocillia may induce hair cell loss and hearing impairments. Taken together, our data indicates that LKB1 is required for the development and maintenance of stereocilia in the inner ear. PMID- 26274332 TI - An Eye-Tracking Study of Multiple Feature Value Category Structure Learning: The Role of Unique Features. AB - We examined whether the degree to which a feature is uniquely characteristic of a category can affect categorization above and beyond the typicality of the feature. We developed a multiple feature value category structure with different dimensions within which feature uniqueness and typicality could be manipulated independently. Using eye tracking, we found that the highest attentional weighting (operationalized as number of fixations, mean fixation time, and the first fixation of the trial) was given to a dimension that included a feature that was both unique and highly typical of the category. Dimensions that included features that were highly typical but not unique, or were unique but not highly typical, received less attention. A dimension with neither a unique nor a highly typical feature received least attention. On the basis of these results we hypothesized that subjects categorized via a rule learning procedure in which they performed an ordered evaluation of dimensions, beginning with unique and strongly typical dimensions, and in which earlier dimensions received higher weighting in the decision. This hypothesis accounted for performance on transfer stimuli better than simple implementations of two other common theories of category learning, exemplar models and prototype models, in which all dimensions were evaluated in parallel and received equal weighting. PMID- 26274333 TI - Correction: Network Models of Frequency Modulated Sweep Detection. PMID- 26274335 TI - Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009. AB - Hepatocellular carcinoma (HCC) is increasingly reported in patients with nonalcoholic fatty liver disease (NAFLD). Our aim was to assess the prevalence and mortality of patients with NAFLD-HCC. We examined Surveillance, Epidemiology and End Results (SEER) registries (2004-2009) with Medicare-linkage files for HCC, which was identified by the International Classification of Diseases for Oncology, third edition codes using topography and morphology codes 8170-8175. Medicare-linked data was used to identify NAFLD, hepatitis C virus (HCV), hepatitis B virus (HBV), alcoholic liver disease (ALD), and other liver disease using International Classification of Diseases, Ninth Revision, Clinical Modification codes. NAFLD was also defined by clinical diagnosis (cryptogenic cirrhosis, obese-diabetics with cryptogenic liver disease). A logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of HCC. In addition, adjusted hazard ratios for 1-year mortality were estimated by Cox's proportional hazard regression. A total of 4,929 HCC cases and 14,937 controls without HCC were included. Of the HCC cases, 54.9% were related to HCV, 16.4% to ALD, 14.1% to NAFLD, and 9.5% to HBV. Across the 6-year period (2004 to 2009), the number of NAFLD-HCC showed a 9% annual increase. NAFLD-HCC were older, had shorter survival time, more heart disease, and were more likely to die from their primary liver cancer (all P < 0.0001). Of those who received a transplant after HCC (n = 488), only 5% were related to NAFLD-HCC. In multivariate analysis, NAFLD increased the risk of 1-year mortality (OR, 1.21; 95% CI: 1.01-1.45). Additionally, older age, lower income, unstaged HCC increased risk of 1-year mortality while receiving a liver transplant (LT), and having localized tumor stage were protective (all P < 0.05). CONCLUSIONS: NAFLD is becoming a major cause of HCC in the United States. NAFLD HCC is associated with shorter survival time, more advanced tumor stage, and lower possibility of receiving a LT. PMID- 26274334 TI - Ultrasonic measurement of the effects of light irradiation and presence of water on the polymerization of self-adhesive resin cement. AB - Self-adhesive resin cements are useful in restorations because they reduce the number of clinical steps involved in the restoration process. This study evaluated, using ultrasonic measurements, the influence of light irradiation and the presence of water on the polymerization behavior and elastic modulus of a self-adhesive resin cement. A self-adhesive resin cement (RelyX Unicem 2 Automix) or a resin cement (RelyX ARC) was inserted into a transparent mold on a sample stage, and the presence of water and effect of light-irradiation were evaluated. The transit time of a sonic wave through the cement disk was divided by the specimen thickness to obtain the sonic velocity, and longitudinal and shear waves were used to determine the elastic modulus. When the resin cements were light irradiated, the sonic velocity rapidly increased and plateaued at 2,500-2,700 m s 1 . When the cements were not irradiated, the rates of increase in the sonic velocity were reduced. When water was applied to the sample stage, the sonic velocity was reduced. The elastic modulus values of the specimens ranged from 9.9 to 15.9 GPa after 24 h. The polymerization behavior of self-adhesive resin cements is affected by the polymerization mode and the presence of water. PMID- 26274336 TI - L-asparaginase and venous thromboembolism in acute lymphocytic leukemia. AB - The occurrence of venous thromboembolism (VTE) in acute lymphocytic leukemia patients receiving L-asparaginase therapy may cause significant morbidity, neurological sequela and possibly worse outcomes. The prophylactic use of antithrombin infusion (to keep antithrombin activity >60%) or low molecular weight heparin (LMWH) may reduce the risk of VTE. The decision to continue L asparaginase therapy after the development of VTE should be based on anticipated benefits, severity of VTE and the ability to continue therapeutic anticoagulation. In patients receiving asparaginase rechallenge, the use of therapeutic LMWH, monitoring of anti-Xa level and antithrombin level are important. Novel oral anticoagulants are not dependent on antithrombin level, hence offer theoretical advantages over LMWH for the prevention and therapy of asparaginase-related VTE. PMID- 26274337 TI - Variable presence of 5-methylcytosine in commercial RNA and DNA. PMID- 26274339 TI - Identification of intermediates in the biosynthesis of PR toxin by Penicillium roqueforti. AB - The sesquiterpenoid 7-epi-neopetasone was synthesized via the Wieland-Miescher ketone. The compound was identical to a previously tentatively identified headspace constituent of Penicillium roqueforti. Feeding experiments with (13) C labeled mevalonolactone isotopomers demonstrated that oxidation at C12 and an isomerization of the C11?C12 to a C7?C11 double bond must occur independently and not via a C7-C11-C12 allyl radical in one step. Feeding with (11,12,13-(13) C3 ) 7-epi-neopetasone resulted in labelling of the PR toxin, thus establishing this compound as a newly identified pathway intermediate. PMID- 26274338 TI - A Multistep, Consensus-Based Approach to Organ Allocation in Liver Transplantation: Toward a "Blended Principle Model". AB - Since Italian liver allocation policy was last revised (in 2012), relevant critical issues and conceptual advances have emerged, calling for significant improvements. We report the results of a national consensus conference process, promoted by the Italian College of Liver Transplant Surgeons (for the Italian Society for Organ Transplantation) and the Italian Association for the Study of the Liver, to review the best indicators for orienting organ allocation policies based on principles of urgency, utility, and transplant benefit in the light of current scientific evidence. MELD exceptions and hepatocellular carcinoma were analyzed to construct a transplantation priority algorithm, given the inequity of a purely MELD-based system for governing organ allocation. Working groups of transplant surgeons and hepatologists prepared a list of statements for each topic, scoring their quality of evidence and strength of recommendation using the Centers for Disease Control grading system. A jury of Italian transplant surgeons, hepatologists, intensivists, infectious disease specialists, epidemiologists, representatives of patients' associations and organ-sharing organizations, transplant coordinators, and ethicists voted on and validated the proposed statements. After carefully reviewing the statements, a critical proposal for revising Italy's current liver allocation policy was prepared jointly by transplant surgeons and hepatologists. PMID- 26274341 TI - Editorial Retraction. PMID- 26274340 TI - Robotic trans-axillary and retro-auricular thyroid surgery. AB - Remote access approaches for thyroid surgery using surgical incisions placed outside the neck, including the axillary, chest and the retro-auricular region have gained interest due to the social stigmatization of young females with a visible neck scar. These novel approaches have been reported to be safe and feasible approaches for thyroid surgery in a select group of patients. Herein, we will discuss different aspects of the current robotic approaches. PMID- 26274342 TI - Outcomes and Risk Factors for Complications of Laser Ablation for Thyroid Nodules: A Multicenter Study on 1531 Patients. AB - BACKGROUND: Image-guided laser ablation therapy (LAT) of benign thyroid nodules demonstrated favorable results in randomized trials with fixed modalities of treatment. The aim of this retrospective multicenter study was to assess the effectiveness, tolerability, and complications of LAT in a large consecutive series of patients from centers using this technique in their routine clinical activity. PATIENTS: Clinical records of 1534 consecutive laser-treated nodules in 1531 patients from eight Italian thyroid referral centers were assessed. Inclusion criteria were as follows: solid or mixed nodules with fluid component up to 40%; benign cytological findings; and normal thyroid function. METHODS: LAT was performed with a fixed-power protocol, whereas the number of applicators and illumination times were different according to target size. From one to three illuminations with pullback technique and with a total energy delivery based on the nodule volume were performed during the same session. Patients were evaluated during LAT, within 30 days, and 12 months after the procedure. RESULTS: Total number of treatments was 1837; 1280 (83%) of nodules had a single LAT session. Mean nodule volume decreased from 27 +/- 24 mL at baseline to 8 +/- 8 mL 12 months after treatment (P < .001). Mean nodule volume reduction was 72% +/- 11% (range 48%-96%). This figure was significantly greater in mixed nodules (79% +/- 7%; range 70%-92%) because they were drained immediately before laser illumination. Symptoms improved from 49% to 10% of cases (P < .001) and evidence of cosmetic signs from 86% to 8% of cases (P < .001). Seventeen complications (0.9%) were registered. Eight patients (0.5%) experienced transitory voice changes that completely resolved at the ear-nose-throat examination within 2-84 days. Nine minor complications (0.5%) were reported. No changes in thyroid function or autoimmunity were observed. CONCLUSIONS: Real practice confirmed LAT as a clinically effective, reproducible, and rapid outpatient procedure. Treatments were well tolerated and risk of major complications was very low. PMID- 26274344 TI - Screening Tests for Cushing's Syndrome: Urinary Free Cortisol Role Measured by LC MS/MS. AB - INTRODUCTION AND AIM: As initial screening for Cushing's syndrome (CS), The Endocrine Society guidelines recommend one of the following: the 1-mg dexamethasone suppression test (DST) or late-night salivary cortisol (LNSC) or urinary free cortisol (UFC) measurement. We examined the diagnostic performance of the above-mentioned tests in a series of patients. MATERIALS AND METHODS: We retrospectively analyzed 137 patients with clinical conditions suggestive of hypercortisolism: 38 with confirmed CS diagnosis and 99 without (termed non-CS). UFC was measured by liquid chromatography tandem-mass spectrometry, whereas LNSC by the radioimmunometric method and serum cortisol were measured by a chemiluminescence immunoassay. RESULTS: Comparing CS vs non-CS, a cutoff of 138 nmol/L after 1-mg DST revealed the best specificity (SP; 97%), whereas the 50 nmol/L cutoff confirmed the best sensitivity (SE; 100%); the SE and SP for LNSC greater than 14.46 nmol/L were, respectively, 84% and 89%, whereas the SE and SP for UFC greater than 170 nmol per 24 hours, they were 97% and 91%. Overall, UFC revealed both a combined higher positive and a lower negative likelihood ratio among first-line tests (respectively 10.7 and 0.03). Computing a receiver operating curve -contrast analysis to compare the power of each single test with that of the others, alone or combined (DST+LNSC, DST+UFC, and LNSC+UFC) or with that of all the tests together (DST+LNSC+UFC), the UFC assay was at least as good as all the other possible combinations. CONCLUSIONS: Measuring UFC by liquid chromatography tandem-mass spectrometry achieves the best accuracy in diagnosing CS among patients presenting with suspected hypercortisolism. PMID- 26274343 TI - PTCSC3 Is Involved in Papillary Thyroid Carcinoma Development by Modulating S100A4 Gene Expression. AB - CONTEXT: We previously showed that a long noncoding RNA gene, PTCSC3, located close to the variant rs944289 that predisposes to papillary thyroid carcinoma (PTC) might target the S100A4 gene. OBJECTIVE: The aim was to investigate the impact of PTCSC3 on S100A4 expression and its role in cancer development. DESIGN: S100A4 abundance was analyzed by quantitative PCR (qPCR) in unaffected and tumor tissue from n = 73 PTC patients. The expression of PTCSC3 and S100A4 was studied in BCPAP and TPC-1 cell lines with forced expression of PTCSC3 by qPCR. Expression of S100A4 target genes (VEGF and MMP-9) was studied in the BCPAP cell line with forced expression of PTCSC3 by qPCR, reverse transcriptase PCR, and Western blot. The impact of PTCSC3 on BCPAP motility and invasiveness was analyzed by the Transwell and Matrigel assays, respectively. SETTING: This was a laboratory-based study using cells from clinical samples and thyroid cancer cell lines. MAIN OUTCOME AND MEASURE: We aimed to find evidence for a link between the expression of PTCSC3 and thyroid carcinogenesis. RESULTS: Expression data from PTC cell lines pinpointed S100A4 as the most significantly downregulated gene in the presence of PTCSC3. S100A4 was upregulated in tumor tissue (P = 9.33 * 10( 7)) while PTCSC3 was strongly downregulated (P = 2.2 * 10(-16)). S100A4 transcription was moderately correlated with PTCSC3 expression in unaffected thyroid tissue (r = 0.429, P = .0001), and strongly in unaffected tissue of patients with the risk allele of rs944289 (r = 0.685, P = 7.88 * 10(-5)). S100A4, VEGF, and MMP-9 were suppressed in the presence of PTCSC3 (P = .0051, P = .0090, and P =.0037, respectively). PTC cells expressing PTCSC3 showed reduction in motility and invasiveness (P = 4.52 * 10(-5) and P = 1.0 * 10(-4), respectively). CONCLUSIONS: PTCSC3 downregulates S100A4, leading to a reduction in cell motility and invasiveness. We propose that PTCSC3 impacts PTC predisposition and carcinogenesis through the S100A4 pathway. PMID- 26274345 TI - One-Hour Postload Hyperglycemia Is a Stronger Predictor of Type 2 Diabetes Than Impaired Fasting Glucose. AB - CONTEXT: Subjects with normal glucose tolerance (NGT) but 1-h postload glucose >= 155 mg/dL (NGT-1h-high) exhibit an intermediate cardiometabolic risk profile between individuals with NGT and impaired glucose tolerance (IGT). OBJECTIVE: This study aimed to evaluate whether NGT-1h-high subjects have different cardiometabolic characteristics and an increased risk of type 2 diabetes compared with individuals with isolated impaired fasting glucose (IFG). SETTING, DESIGN, AND PATIENTS: A cross-sectional analysis was performed on 595 nondiabetic subjects who underwent an oral glucose tolerance test and an euglycemic hyperinsulinemic clamp in an ambulatory care setting. In addition, a longitudinal analysis was performed on 392 individuals, who were reexamined after a followup of 5.2 +/- 0.9 y. MAIN OUTCOME MEASURES: Insulin sensitivity, beta-cell function, and risk of developing diabetes were measured. RESULTS: Subjects with NGT-1h-high have a significant reduction of peripheral insulin sensitivity and beta-cell function, assessed by the disposition index, compared with either 1-h postload glucose < 155 mg/dL (NGT-1h-low) or IFG individuals, but not compared with IGT. Among the 392 subjects studied in the longitudinal analysis the incidence rate of type 2 diabetes over the follow-up period was 2.9, 16.7, 12.5, and 31.4% for subjects with NGT-1h-low, NGT-1h-high, IFG, and IGT, respectively. In a Cox proportional hazard regression analysis the risk of developing diabetes for NGT 1h-high subjects was 4.02 (95% confidence interval [CI] 1.06-15.26); an even higher risk (6.67; 95% CI, 2.09-21.24) was observed in subjects with IGT, but not in the isolated IFG group (1.91; 95% CI, 0.44-8.29). CONCLUSIONS: NGT-1h-high subjects exhibit a higher risk of developing diabetes than those with IFG or NGT 1h-low, likely due to decreased insulin sensitivity and beta-cell function. PMID- 26274346 TI - FGF21 Response to Critical Illness: Effect of Blood Glucose Control and Relation With Cellular Stress and Survival. AB - CONTEXT: Critical illness is hallmarked by mitochondrial damage, which is attenuated by targeting normoglycemia. Mitochondrial dysfunction induces fibroblast growth factor-21 (FGF21) via the integrated stress response (ISR). OBJECTIVE: We evaluated whether critical illness elevates serum FGF21 concentrations and whether targeting normoglycemia (80-110 mg/dL) with insulin vs tolerating hyperglycemia may lower serum FGF21 by attenuating mitochondrial dysfunction and the ISR. SETTING/DESIGN: We quantified serum FGF21 concentrations in critically ill patients. To allow tissue analyses, including hepatic fgf21 expression in relation with mitochondrial function and ISR markers, we studied critically ill rabbits. Patients and rabbits were randomized to hyper- or normoglycemia. Patients/Other Participants: We studied 405 fed critically ill patients vs 20 matched non-critically ill control subjects as well as 26 critically ill rabbits vs 13 healthy rabbits. INTERVENTIONS: Insulin was infused to control blood glucose. MAIN OUTCOME MEASURES AND RESULTS: Serum FGF21 concentrations upon intensive care unit admission were 8-fold higher than in control subjects (P < .0001), decreased with time, but always remained higher in nonsurvivors than survivors (P <= .006). Maintaining normoglycemia lowered serum FGF21 (P = .01), statistically explaining at least part of its mortality benefit. In ill rabbits, hepatic fgf21 expression was substantially increased (P < .0001) and was tightly correlated with mitochondrial dysfunction (all R(2) >= 0.49; all P <= .0006 for complex I and V) and ISR markers on day 3 (R(2) >= 0.73; P <= .0001), all lowered by targeting normoglycemia. CONCLUSION: Critical illness is a potent inducer of serum FGF21 and of liver fgf21 expression, possibly driven at least in part by mitochondrial damage and the ISR, which were all attenuated by targeting normoglycemia. PMID- 26274347 TI - Progressive Pseudorheumatoid Dysplasia With Delayed Diagnosis. PMID- 26274348 TI - Very Facile Polarity Umpolung and Noncovalent Functionalization of Inorganic Nanoparticles: A Tool Kit for Supramolecular Materials Chemistry. AB - The facile assembly of shell-by-shell (SbS)-coated nanoparticles [TiO2 PAC16]@shell 1-7 (PAC16 = hexadecylphosphonic acid), which are soluble in water and can be isolated as stable solids, is reported. In these functional architectures, an umpolung of dispersibility (organic apolar versus water) was accomplished by the noncovalent binding of ligands 1-7 to titania nanoparticles [TiO2-PAC16] containing a first covalent coating with PAC16. Ligands 1-7 are amphiphilic and form the outer second shell of [TiO2-PAC16]@shell 1-7. The tailor designed dendritic building blocks 3-5 contain negative and positive charges in the same molecule, and ligands 6 and 7 contain a perylenetetracarboxylic acid dimide (PDI) core (6/7) as a photoactive reporter component. In the redox and photoactive system [TiO2-PAC16]@shell 7, electronic communication between the inorganic core to the PDI ligands was observed. PMID- 26274349 TI - What is the best strategy for retaining gestures in working memory? AB - This study aimed to determine whether the recall of gestures in working memory could be enhanced by verbal or gestural strategies. We also attempted to examine whether these strategies could help resist verbal or gestural interference. Fifty four participants were divided into three groups according to the content of the training session. This included a control group, a verbal strategy group (where gestures were associated with labels) and a gestural strategy group (where participants repeated gestures and were told to imagine reproducing the movements). During the experiment, the participants had to reproduce a series of gestures under three conditions: "no interference", gestural interference (gestural suppression) and verbal interference (articulatory suppression). The results showed that task performance was enhanced in the verbal strategy group, but there was no significant difference between the gestural strategy and control groups. Moreover, compared to the "no interference" condition, performance decreased in the presence of gestural interference, except within the verbal strategy group. Finally, verbal interference hindered performance in all groups. The discussion focuses on the use of labels to recall gestures and differentiates the induced strategies from self-initiated strategies. PMID- 26274350 TI - Relationship between antidepressant prescription and breast cancer: a population based study in Taiwan. AB - OBJECTIVE: To investigate the association between antidepressant prescription and breast cancer. METHODS: The National Health Research Institute in Taiwan provided a database of 1 000 000 random subjects for this study. We identified 14 737 new antidepressant female users who were more than 15 years old during 1999-2005 with at least 10 prescriptions and one year exposure to an antidepressant. These were matched 1:1 by age and residence to non-antidepressant users from the same database to compare the risk of breast cancer. RESULTS: In a model adjusted by age, residence, insurance amount, and depressive disorder, antidepressant prescription was not associated with breast cancer risk. This held true for both selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressants. CONCLUSIONS: There was no evidence for an association between antidepressant prescription and the risk of breast cancer. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26274351 TI - Comparative evaluation of the depletion-red cell exchange program with the Spectra Optia and the isovolemic hemodilution-red cell exchange method with the COBE Spectra in sickle cell disease patients. AB - BACKGROUND: This study aims to compare in patients with sickle cell disease (SCD), the technical performance and packed red blood cell unit consumption between the automated depletion/Red Blood Cell exchange (RBCx) program (Spectra Optia Apheresis System) with the isovolemic hemodilution (IHD)/RBCx procedure (COBE Spectra Apheresis System) in a routine clinical setting. METHODS: We retrospectively reviewed the data of 23 patients treated between October 2010 and August 2013 who underwent repeated RBCx on both apheresis systems for preventive indications. Each patient was their own control and had undergone two procedures on each system, totaling 46 sessions per group. On Spectra Optia, we performed the automated depletion/RBCx program. For COBE Spectra, we used a modified IHD/RBCx protocol. All patients had an initial 250 mL depletion offset by a 5% albumin prior to the exchange procedure, for the respective device, with leucodepleted Rh/Kell compatible and cross-matched RBC packs. RESULTS: All procedures were well tolerated except three mild febrile nonhemolytic reactions. Postprocedure hemoglobin S (HbS), fraction of cells remaining (FCR), procedure duration and processed blood and anticoagulant volumes were comparable in the two groups. However, the RBCx volume was significantly higher for the Spectra Optia group (+71 mL, P = 0.01), with no significant difference in the number of RBC units used. CONCLUSIONS: Technical performance and packed RBC unit consumption were not compromised when switching from the COBE Spectra IHD/RBCx protocol to the depletion/RBCx protocol on the Spectra Optia. Tolerability was equal for both protocols. J. Clin. Apheresis 31:429-433, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26274353 TI - Student assistantship programme in practice: First hand experience at Cardiff University. PMID- 26274354 TI - Beyond limitations: Improving how we handle uncertainty in health professions education research. AB - The researchers' assumptions invariably influence research outcomes. This is true for both qualitative and quantitative studies. Assumptions or choices regarding underlying theories, causal relations, study setting and population, sampling strategies, participant non-response, data collection, data analysis, and researchers' perceptions and interpretations of results are among factors that can induce uncertainty in research findings. Researchers tend to treat these factors as potential study limitations, but how they may impact research findings is rarely explicated and, therefore, mostly unknown. In this article, we approach uncertainty as unavoidable in research and argue that communicating about uncertainty can inform researchers, policy makers and practitioners about the validity and applicability of the study findings for their interests and contexts. We illustrate approaches to address, interpret, and explicate uncertainty in medical education research in both qualitative and quantitative paradigms. Across research paradigms, we call on researchers to consider the uncertainty in their research findings, employ appropriate methods to explore its extent and effects in their work, and communicate it explicitly in their research papers. This will help to advance our understanding of the nature and implications of the emerging knowledge in our field. PMID- 26274352 TI - Isolation and Functional Analysis of an Immortalized Murine Cementocyte Cell Line, IDG-CM6. AB - The dental cementum covering the tooth root is similar to bone in several respects but remains poorly understood in terms of development and differentiation of cementoblasts, as well as the potential function(s) of cementocytes residing in the cellular cementum. It is not known if the cementocyte is a dynamic actor in cementum metabolism, comparable to the osteocyte in the bone. Cementocytes exhibit irregular spacing and lacunar shape, with fewer canalicular connections compared with osteocytes. Immunohistochemistry and quantitative PCR (qPCR) revealed that the in vivo expression profile of cementocytes paralleled that of osteocytes, including expression of dentin matrix protein 1 (Dmp1/DMP1), Sost/sclerostin, E11/gp38/podoplanin, Tnfrsf11b (osteoprotegerin [OPG]), and Tnfsf11 (receptor activator of NF-kappaB ligand [RANKL]). We used the Immortomouse(+/-); Dmp1-GFP(+/-) mice to isolate cementocytes as Dmp1-expressing cells followed by immortalization using the interferon (IFN)-gamma-inducible promoter driving expression of a thermolabile large T antigen to create the first immortalized line of cementocytes, IDG-CM6. This cell line reproduced the expression profile of cementocytes observed in vivo, including alkaline phosphatase activity and mineralization. IDG-CM6 cells expressed higher levels of Tnfrsf11b and lower levels of Tnfsf11 compared with IDG-SW3 osteocytes, and under fluid flow shear stress, IDG-CM6 cells significantly increased OPG while decreasing RANKL, leading to a significantly increased OPG/RANKL ratio, which would inhibit osteoclast activation. These studies indicate similarities yet potentially important differences in the function of cementocytes compared with osteocytes and support cementocytes as mechanically responsive cells. PMID- 26274355 TI - Learning to prescribe in a student-run clinic. PMID- 26274356 TI - Should the General Medical Council explore the use of digital badges? PMID- 26274357 TI - Tablet- or iPAD-based marking of OSCEs and MMIs: An imaginative cost-saving approach. PMID- 26274358 TI - Response to "Different forms of intuitions". PMID- 26274359 TI - The hidden and informal curriculum across the continuum of training: A cross sectional qualitative study. AB - PURPOSE: The hidden and informal curricula refer to learning in response to unarticulated processes and constraints, falling outside the formal medical curriculum. The hidden curriculum has been identified as requiring attention across all levels of learning. We sought to assess the knowledge and perceptions of the hidden and informal curricula across the continuum of learning at a single institution. METHODS: Focus groups were held with undergraduate and postgraduate learners and faculty to explore knowledge and perceptions relating to the hidden and informal curricula. Thematic analysis was conducted both inductively by research team members and deductively using questions structured by the existing literature. RESULTS: Participants highlighted several themes related to the presence of the hidden and informal curricula in medical training and practice, including: the privileging of some specialties over others; the reinforcement of hierarchies within medicine; and a culture of tolerance towards unprofessional behaviors. Participants acknowledged the importance of role modeling in the development of professional identities and discussed the deterioration in idealism that occurs. CONCLUSIONS: Common issues pertaining to the hidden curriculum exist across all levels of learners, including faculty. Increased awareness of these issues could allow for the further development of methods to address learning within the hidden curriculum. PMID- 26274360 TI - Treating your own students: Ethical challenges for mental health professionals. PMID- 26274361 TI - Installing multifunctionality on titanium with RGD-decorated polyurethane polyurea roxithromycin loaded nanoparticles: toward new osseointegrative therapies. AB - A novel class of polyurethane-polyurea nanoparticles (PUUa NPs) to install multifunctionality on biomaterials is presented. Biofunctionalization of titanium with roxithromycin loaded RGD-decorated PUUa NPs results in an outstanding improvement of osteoblast adhesion and strong suppression of bacterial attachment. This strategy represents a powerful approach to enhance the osseointegration of implant materials. PMID- 26274362 TI - Physiotherapy for Patients on Awake Extracorporeal Membrane Oxygenation: A Systematic Review. AB - BACKGROUND AND PURPOSE: Extracorporeal membrane oxygenation (ECMO) is used as temporary life support in subjects with potentially reversible respiratory/cardiac failure. The principal purpose of this review was to assess the characteristics and potential advantages of physiotherapeutic interventions in subjects on awake ECMO support. METHODS: Seven databases were interrogated: we searched titles, abstracts and keywords using the Medical Subject Headings terms 'extracorporeal membrane oxygenation' and 'rehabilitation' linked with the Boolean operator 'AND'. RESULTS AND CONCLUSION: In total, 216 citations were retrieved. Nine citations satisfied our inclusion criteria and were subjected to full-text analysis. The numbers of patients enrolled in the included studies (most of which were case series) were low (n = 52). We found no prospective studies or randomized controlled trials. Overall, subjects on awake ECMO usually received a combination of passive and active physiotherapy, and most achieved an acceptable degree of autonomy after treatment. Emerging research in the field affords preliminary evidence supporting the safety of early mobilization and ambulation in patients on awake veno-venous ECMO support. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26274363 TI - Corrigendum: Resonantly excited precession motion of three-dimensional vortex core in magnetic nanospheres. PMID- 26274364 TI - What's New in Shock? September 2015. PMID- 26274366 TI - Shock in the First 24 h of Intensive Care Unit Stay: Observational study of Protocol-Based Fluid Management. PMID- 26274365 TI - Does Insulin Protect the Brain in Mice and Man with Sepsis? PMID- 26274367 TI - Shock in the First 24 h of Intensive Care Unit Stay: Observational Study of Protocol-Based Fluid Management: Reply. PMID- 26274368 TI - Peptide flatlandia: a new-concept peptide for positioning of electroactive probes in proximity to a metal surface. AB - A helical hexapeptide was designed to link in a rigid parallel orientation to a gold surface. The peptide sequence of the newly synthesized compound is characterized by the presence of two 4-amino-1,2-dithiolane-4-carboxylic acid (Adt) residues (positions 1 and 4) to promote a bidentate interaction with the gold surface, two L-Ala residues (positions 2 and 5) and two-aminoisobutyric acid (Aib) residues (positions 3 and 6) to favor a high population of the 310-helix conformation. Furthermore, a ferrocenoyl (Fc) probe was inserted at the N terminus to investigate the electronic conduction properties of the peptide. X Ray photoelectron spectroscopy and scanning tunneling microscopy techniques were used to characterize the binding of the peptide to the gold surface and the morphology of the peptide layer, respectively. Several electrochemical (cyclic voltammetry, chronoamperometry, square wave voltammetry) techniques were applied to analyze the electrochemical activity of the Fc probe, along with the influence of the peptide 3D-structure and the peptide layer morphology on electron transfer processes. PMID- 26274369 TI - Increased peripheral vascular resistance in male patients with traumatic lower limb amputation: one piece of the cardiovascular risk puzzle. AB - AIM: The increased morbidity and mortality in traumatic lower limb amputees can be explained by the development of risk factors, among which high blood pressure plays an important role. However, the possible mechanisms underlying increased blood pressure levels observed in this population remain unclear. Thus, we aimed to test the hypothesis that peripheral vascular resistance is increased at rest in patients with traumatic lower limb amputation. PATIENTS AND METHODS: In a cross-sectional study, eight patients with traumatic unilateral lower limb amputation (amputee group) and eight healthy individuals without amputation (control group) were included. Resting blood pressure, heart rate, and forearm blood flow were recorded simultaneously and thus, forearm vascular resistance was calculated. RESULTS: The amputee group showed higher systolic (126+/-2 vs. 118+/ 5 mmHg, P<0.01), diastolic (78+/-2 vs. 63+/-3 mmHg, P<0.01), mean blood pressure (94+/-2 vs. 81+/-3 mmHg, P<0.01), and heart rate (74+/-5 vs. 65+/-8 bpm, P=0.02) compared with the control group. Despite the similar forearm blood flow response between groups, patients with traumatic lower limb amputation presented increased peripheral vascular resistance at rest compared with the control group (31.3+/ 3.8 vs. 25.7+/-6.5 U, P=0.05). CONCLUSION: Patients with traumatic amputation present increased peripheral vascular resistance. Our findings clarify one possible mechanism underlying the higher blood pressure levels observed in this population. PMID- 26274370 TI - Exploration of minimum energy conical intersection structures of small polycyclic aromatic hydrocarbons: toward an understanding of the size dependence of fluorescence quantum yields. AB - Minimum energy conical intersection (MECI) geometries were searched for polycyclic aromatic hydrocarbons (PAHs) consisting of up to 26 atoms. The energy barriers to the obtained MECIs showed a correlation with their fluorescence quantum yields. This provides a theoretical rationale for the size dependence of the fluorescence quantum yields seen in these PAHs. PMID- 26274372 TI - Effect of 12 Weeks of Periodized Resistance Training Upon Total Plasma Adiponectin Concentration in Healthy Young Men. AB - The effects of resistance training on adiponectin have thus far yielded equivocal results. However, the effect of periodized resistance training on plasma adiponectin in offspring of type 2 diabetic and nondiabetic (ND) parents (first degree family history) has yet to be determined. Untrained healthy young men with and without a first-degree family history of type 2 diabetes were assigned to an exercise intervention group (E) or an active control group (C). The E group performed a 12-week periodized resistance training program, whereas the C group did not participate in any structured exercise program. Fasting plasma samples were obtained pre- and posttraining. Total plasma adiponectin changed significantly in the E group (33.7 +/- 14.7%, p = 0.025) but not in the C group (10.8 +/- 19.2%). Offspring of type 2 diabetic parents subjects had significantly greater improvements in plasma adiponectin (69.3 +/- 34.8%) compared with ND subjects (-3.2 +/- 29.9%, p = 0.046). Regular aerobic exercise was significantly correlated with average plasma adiponectin (r = 0.32), whereas first-degree family history of type 2 diabetes (r = -0.58) and decreases in body fat percentage (r = -0.77) were inversely correlated with average plasma adiponectin. Periodized high-intensity resistance training seems to increase plasma adiponectin, particularly in individuals with a first-degree family history of type 2 diabetes or those who experience a significant loss of fat mass. The direct correlation between regular aerobic exercise and adiponectin further suggests that a combination of aerobic and resistance training yields greater improvements in plasma adiponectin compared with resistance training alone. PMID- 26274371 TI - Fluorescence Biomembrane Force Probe: Concurrent Quantitation of Receptor-ligand Kinetics and Binding-induced Intracellular Signaling on a Single Cell. AB - Membrane receptor-ligand interactions mediate many cellular functions. Binding kinetics and downstream signaling triggered by these molecular interactions are likely affected by the mechanical environment in which binding and signaling take place. A recent study demonstrated that mechanical force can regulate antigen recognition by and triggering of the T-cell receptor (TCR). This was made possible by a new technology we developed and termed fluorescence biomembrane force probe (fBFP), which combines single-molecule force spectroscopy with fluorescence microscopy. Using an ultra-soft human red blood cell as the sensitive force sensor, a high-speed camera and real-time imaging tracking techniques, the fBFP is of ~1 pN (10(-12) N), ~3 nm and ~0.5 msec in force, spatial and temporal resolution. With the fBFP, one can precisely measure single receptor-ligand binding kinetics under force regulation and simultaneously image binding-triggered intracellular calcium signaling on a single live cell. This new technology can be used to study other membrane receptor-ligand interaction and signaling in other cells under mechanical regulation. PMID- 26274373 TI - Nanoparticle stability in biologically relevant media: influence of polymer architecture. AB - We have contrasted the behavior of nanoparticles formed by the self-assembly of polymers based on poly(ethylene glycol) (PEG) and poly(D,L-lactide), with linear, linear-dendritic and bottle-brush architectures in biologically relevant media. Polymer PEG content ranged between 14% and 46% w/w, and self-assembly was triggered by a rapid and large change in solvent quality inside a four-stream vortex mixer. We examined nanoparticle interaction with human serum albumin (HSA), and solute release in the presence of fetal bovine serum. Dynamic light scattering data showed that PEG surface brushes of all nanoparticles provided effective steric stabilization, thus limiting their interaction with human serum albumin. Calorimetric experiments revealed that nanoparticle-HSA interaction was relatively weak and enthalpically driven, whereas dynamic light scattering results of incubated nanoparticles showed the absence of larger aggregates for most of the polymers examined. Solute core partitioning was examined by the loss of Forster resonance energy transfer (FRET) from a core-loaded donor-acceptor pair. The rate and magnitude of FRET efficiency loss was strongly dependent on the polymer architecture, and was found to be lowest for the bottle-brush, attributed to its covalent nature. Collectively, these findings are expected to impact the molecular design of increasingly stable polymeric carriers for drug delivery applications. PMID- 26274374 TI - Complex Information for Anesthesiologists Presented Quickly and Clearly. PMID- 26274376 TI - Perceived grip, balance and comfort of yoga and gym mats correlate with biomechanical and mechanical assessment. PMID- 26274375 TI - An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells. AB - In this work we describe a novel approach that combines ex vivo drug sensitivity assays and digital image analysis to estimate chemosensitivity and heterogeneity of patient-derived multiple myeloma (MM) cells. This approach consists in seeding primary MM cells freshly extracted from bone marrow aspirates into microfluidic chambers implemented in multi-well plates, each consisting of a reconstruction of the bone marrow microenvironment, including extracellular matrix (collagen or basement membrane matrix) and stroma (patient-derived mesenchymal stem cells) or human-derived endothelial cells (HUVECs). The chambers are drugged with different agents and concentrations, and are imaged sequentially for 96 hr through bright field microscopy, in a motorized microscope equipped with a digital camera. Digital image analysis software detects live and dead cells from presence or absence of membrane motion, and generates curves of change in viability as a function of drug concentration and exposure time. We use a computational model to determine the parameters of chemosensitivity of the tumor population to each drug, as well as the number of sub-populations present as a measure of tumor heterogeneity. These patient-tailored models can then be used to simulate therapeutic regimens and estimate clinical response. PMID- 26274377 TI - Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues. AB - Protein alignments are commonly used to evaluate the similarity of protein residues, and the derived consensus sequence used for identifying functional units (e.g., domains). Traditional consensus-building models fail to account for interpositional dependencies - functionally required covariation of residues that tend to appear simultaneously throughout evolution and across the phylogentic tree. These relationships can reveal important clues about the processes of protein folding, thermostability, and the formation of functional sites, which in turn can be used to inform the engineering of synthetic proteins. Unfortunately, these relationships essentially form sub-motifs which cannot be predicted by simple "majority rule" or even HMM-based consensus models, and the result can be a biologically invalid "consensus" which is not only never seen in nature but is less viable than any extant protein. We have developed a visual analytics tool, StickWRLD, which creates an interactive 3D representation of a protein alignment and clearly displays covarying residues. The user has the ability to pan and zoom, as well as dynamically change the statistical threshold underlying the identification of covariants. StickWRLD has previously been successfully used to identify functionally-required covarying residues in proteins such as Adenylate Kinase and in DNA sequences such as endonuclease target sites. PMID- 26274378 TI - Gene Transfection toward Spheroid Cells on Micropatterned Culture Plates for Genetically-modified Cell Transplantation. AB - To improve the therapeutic effectiveness of cell transplantation, a transplantation system of genetically modified, injectable spheroids was developed. The cell spheroids are prepared in a culture system on micropatterned plates coated with a thermosensitive polymer. A number of spheroids are formed on the plates, corresponding to the cell adhesion areas of 100 um diameter that are regularly arrayed in a two-dimensional manner, surrounded by non-adhesive areas that are coated by a polyethylene glycol (PEG) matrix. The spheroids can be easily recovered as a liquid suspension by lowering the temperature of the plates, and their structure is well maintained by passing them through injection needles with a sufficiently large caliber (over 27 G). Genetic modification is achieved by gene transfection using the original non-viral gene carrier, polyplex nanomicelle, which is capable of introducing genes into cells without disrupting the spheroid structure. For primary hepatocyte spheroids transfected with a luciferase-expressing gene, the luciferase is sustainably obtained in transplanted animals, along with preserved hepatocyte function, as indicated by albumin expression. This system can be applied to a variety of cell types including mesenchymal stem cells. PMID- 26274379 TI - Ultrasound Elastography in Breast Cancer Diagnosis. AB - Ultrasound elastography is an established method for characterization of focal lesions in the breast. Different techniques and analyses of the images may be used for the characterization. This article addresses the use of ultrasound elastography in breast cancer diagnosis. In the first part of the article the techniques behind both strain- and shear-wave-elastography are explained and followed by a section on how to obtain adequate elastography images and measurements. In the second part of the article the application of elastography as an adjunct to B-mode ultrasound in clinical practice is described, and the potential diagnostic gains and limitations of elastography are discussed. PMID- 26274380 TI - Importance of Transvaginal Elastography in the Diagnosis of Uterine Fibroids and Adenomyosis. AB - PURPOSE: To evaluate normal uterine tissue with special regard to age and the presence of uterine fibroids and adenomyosis with transvaginal elastography. MATERIALS AND METHODS: In a prospective study elastographic data of the uterus were obtained in 206 unselected women with transvaginal ultrasound. Women who presented without any uterine pathology in ultrasonography were included in a control group, women with uterine fibroids in a uterine fibroid group, and women with adenomyosis in an adenomyosis group. In the control group strain values were measured at two regions of interest (ROIs) placed one upon the other in the anterior inferior uterine segment during a cycle of compression. The maximum strain ratio (ROI1 / ROI2) was stored as the "age index". In all groups strain values were measured at two ROIs placed side by side in a uterine fibroid (uterine fibroid group) or adenomyosis (adenomyosis group) or healthy homogeneous tissue (control group) and adjacent healthy tissue. Maximum strain ratios (ROI3 / ROI4) were stored as the "lesion index". RESULTS: The "age index" was significantly negatively correlated with the age of the women (r = -0.49, p < 0.001). The median "lesion indices" were significantly (p < 0.001) different between the uterine fibroid, adenomyosis and control groups. Median "lesion indices" were 2.65, 0.44 and 1.19, respectively. CONCLUSION: The "age index" shows that normal uterine tissue has a certain age-dependent stiffness that increases with age. The "lesion index" allows for the assessment of the presence of a uterine fibroid or adenomyosis and helps to differentiate between both focal findings. Thus the use of elastography in addition to conventional ultrasound could help to diagnose uterine focal lesions and may be useful in preoperative planning. PMID- 26274381 TI - Multimodal Ultrasonographic Pathway of Parotid Gland Lesions. AB - Purpose To evaluate a multimodal pathway in solitary circumscribed parotid gland lesions (PL) to predict tumor dignity and to avoid repeat surgery. Materials and Methods 202 patients with PL underwent medical history, clinical examination, high-resolution B-mode ultrasound (US), real-time sonoelastography (RTE), color coded duplex sonography (CDS), and contrast-enhanced ultrasound (CEUS). Malignancy was suspected when: 1. patients reported on previous cutaneous head and neck (H&N) malignancy; 2. patients presented synchronous cutaneous H&N malignancy and/or facial palsy; 3. US visualized poorly defined tumor borders and/or pathological cervical lymph nodes; 4. PL showed poor vascularization in CDS with enhanced perfusion kinetics in CEUS; 5. PL showed moderate/strong vascularization with delayed perfusion kinetics. Intraoperative frozen section was performed in PLs suspicious for malignancy, and surgery was extended when malignancy was confirmed. The sensitivity, specificity, negative, and positive predictive values (NPV/PPV) were calculated. Results Histology revealed 170 benign and 32 malignant PLs. Medical history, clinical examination, and B-mode US identified malignancy with a sensitivity/specificity of 77 %/98 %. After application of CDS and CEUS in the multimodal pathway, the sensitivity of malignant tumors increased to 91 %. The decreased specificity (81 %) was equalized by intraoperative frozen section (PPV 48 %, NPV 98 %). After application of the multimodal pathway, only 1 patient underwent repeat surgery. Conclusion The multimodal pathway is a useful method to predict dignity in PLs and reduces the number of repeat surgeries. PMID- 26274382 TI - Harmonic Contrast-Enhanced Endoscopic Ultrasonography for the Guidance of Fine Needle Aspiration in Solid Pancreatic Masses. AB - Purpose The global accuracy of fine-needle aspiration guided by endoscopic ultrasound (EUS-FNA) for pancreatic adenocarcinoma is about 85 %. The use of contrast agents during EUS to highlight vessels and the necrotic parts of pancreatic masses may improve biopsy guidance. Our aim was to assess whether the guidance of FNA by harmonic contrast-enhanced endoscopic ultrasound (CH-EUS) would increase diagnostic accuracy relative to conventional EUS-FNA in the same pancreatic masses. Patients and Methods In a prospective study, EUS-FNA was performed in patients with pancreatic masses on CT scan, followed by harmonic CH EUS using SonoVue. A second cluster of CH-EUS-FNA was performed on contrast enhanced images. The final diagnosis was based on the results of EUS-FNA and surgery, or the findings after 12 months' follow-up. Results The final diagnosis was adenocarcinoma (n = 35), chronic pancreatitis (n = 10), or other (n = 6). The diagnostic accuracy based on core histology was 78.4 % for EUS-FNA and 86.5 % for CH-EUS-FNA (p = 0.35). The accuracy increased to 94 % when the two methods' results were combined. The two false-negative EUS-FNA cases were correctly appreciated by CH-EUS. Neither core histology size nor the presence of necrosis was significant for the true-positive diagnosis of malignancy. Conclusion CH-EUS FNA had an insignificant incremental effect on diagnostic accuracy compared with conventional EUS-FNA in our small group. The presence of necrosis did not influence the results of CEUS-FNA. Qualitative assessment of the contrast uptake within the lesion was useful in false-negative EUS-FNA cases. PMID- 26274384 TI - Determining The Electromyographic Fatigue Threshold Following a Single Visit Exercise Test. AB - Theoretically, the electromyographic (EMG) fatigue threshold is the exercise intensity an individual can maintain indefinitely without the need to recruit more motor units which is associated with an increase in the EMG amplitude. Although different protocols have been used to estimate the EMG fatigue threshold they require multiple visits which are impractical for a clinical setting. Here, we present a protocol for estimating the EMG fatigue threshold for cycle ergometry which requires a single visit. This protocol is simple, convenient, and completed within 15-20 min, therefore, has the potential to be translated into a tool that clinicians can use in exercise prescription. PMID- 26274385 TI - Is that really my movement? - Students' experiences of a video-supported interactive learning model for movement awareness. AB - Healthcare staff and students have a great risk of developing musculoskeletal symptoms. One cause of this is heavy load related work activities such as manual handling, in which the quality of individual work technique may play a major role. Preventive interventions and well-defined educational strategies to support movement awareness and long-lasting movement changes need to be developed. The aim of the present study was to explore nursing students' experiences of a newly developed interactive learning model for movement awareness. The learning model, which is based on a life-world perspective with focus on interpersonal interaction, has been used with 11 undergraduate students from the second and final year. Each student participated in three individual video sessions with a facilitator. Two individual interviews were carried out with each student during the learning process and one interview 12-18 months after the last session. The interviews were audio-recorded and transcribed verbatim, and a phenomenological hermeneutic method inspired by Paul Ricoeur and described by Lindseth and Norberg was used to interpret the interviews and diary notes. The interpretation resulted in three key themes and nine subthemes. The key themes were; "Obtaining better preconditions for bodily awareness," "Experiencing changes in one's own movement," and "Experiencing challenges in the learning process." The interactive learning model entails a powerful and challenging experience that develops movement awareness. The experience of meaningfulness and usefulness emerges increasingly and alternates with a feeling of discomfort. The learning model may contribute to the body of knowledge of well-defined educational strategies in movement awareness and learning in, for example, preventive interventions and ergonomic education. It may also be valuable in other practical learning situations where movement awareness is required. PMID- 26274387 TI - The role of body mass index, weight change desires and depressive symptoms in the health-related quality of life of children living in urban disadvantage: Testing mediation models. AB - OBJECTIVES: This study was undertaken to ascertain whether or not the body mass index (BMI) of urban disadvantaged children indirectly affects their health related quality of life (HRQoL) through weight change desires and depressive symptoms and whether such mediation is conditional upon age and gender. DESIGN: A total of 255 children aged 7-12 years (50% male) were recruited from 7 schools in urban disadvantaged districts in Ireland using consecutive sampling. A prospective longitudinal design was employed whereby children completed, at two time points, the Kidscreen-27, the Children's Depression Inventory, and the Health Related Behaviour Questionnaire, and had their BMI measured. The analyses involved multiple-, half-longitudinal- and moderated-mediation. RESULTS: Results showed that the depressive symptoms of children wanting to change their weight may have lead, in large part, to poorer HRQoL (specifically psychological well being when considering longitudinal data) rather than weight status per se. The mediation effect of weight change desires occurred regardless of age or gender. CONCLUSIONS: Childhood obesity programmes that traditionally focus on the negatives of obesity and the need to control weight may need to take a more positive approach to health and well-being by, for example promoting intuitive eating, an active lifestyle, body acceptance and good mental health. PMID- 26274386 TI - Microbead Implantation in the Zebrafish Embryo. AB - The zebrafish has emerged as a valuable genetic model system for the study of developmental biology and disease. Zebrafish share a high degree of genomic conservation, as well as similarities in cellular, molecular, and physiological processes, with other vertebrates including humans. During early ontogeny, zebrafish embryos are optically transparent, allowing researchers to visualize the dynamics of organogenesis using a simple stereomicroscope. Microbead implantation is a method that enables tissue manipulation through the alteration of factors in local environments. This allows researchers to assay the effects of any number of signaling molecules of interest, such as secreted peptides, at specific spatial and temporal points within the developing embryo. Here, we detail a protocol for how to manipulate and implant beads during early zebrafish development. PMID- 26274388 TI - Differences in caregivers' psychological distress and associated factors by care recipients' gender and kinship. AB - OBJECTIVES: In this study, we examined the level of psychological distress of Japanese caregivers according to various combinations of the gender of care recipients and the kinship of caregivers (spouse, son, daughter, or daughter-in law). Furthermore, we explored the associated factors that could exacerbate or alleviate psychological distress. METHODS: We utilized a cross-sectional descriptive design and implemented a self-administered questionnaire survey with a two-stage stratified sample of community-dwelling caregivers of frail elderly persons throughout Japan. We surveyed 1279 caregiving families, and 1020 questionnaires were completed by primary caregivers (response rate: 79.8%), with 945 respondents providing data on the Japanese version of the Kessler 6 psychological distress scale (K6). RESULTS: Caregivers' K6 scores varied significantly by care recipients' gender and their relationship with the caregiver. K6 scores were significantly higher among daughters-in-law caring for fathers-in-law than among daughters-in-law caring for mothers-in-law, wives caring for husbands, or daughters or sons caring for mothers. 'Negative influence of caregiving' and 'anxious about continuing caregiving' were factors that commonly exacerbated caregivers' psychological distress. Further analyses involving interactions indicated that the effects of 'anxious about continuing caregiving' and 'personal growth through caregiving' on the psychological distress of daughters-in-law varied by care recipients' gender as did the effects of an alleviating factor, 'keeping their own pace', on daughters. CONCLUSIONS: Psychological distress levels among family caregivers, as well as exacerbating and alleviating factors, varied depending on the gender and kinship of care recipients. PMID- 26274389 TI - Kapitza Resistance between Few-Layer Graphene and Water: Liquid Layering Effects. AB - The Kapitza resistance (RK) between few-layer graphene (FLG) and water was studied using molecular dynamics simulations. The RK was found to depend on the number of the layers in the FLG though, surprisingly, not on the water block thickness. This distinct size dependence is attributed to the large difference in the phonon mean free path between the FLG and water. Remarkably, RK is strongly dependent on the layering of water adjacent to the FLG, exhibiting an inverse proportionality relationship to the peak density of the first water layer, which is consistent with better acoustic phonon matching between FLG and water. These findings suggest novel ways to engineer the thermal transport properties of solid liquid interfaces by controlling and regulating the liquid layering at the interface. PMID- 26274390 TI - Topological Study of the Structures of Heterochiral Peptides Containing Equal Amounts of l-Leu and d-Leu. AB - We designed and synthesized two dodecapeptides, Boc-(l-Leu-l-Leu-Aib-d-Leu-d-Leu Aib)2-OMe (5) and Boc-l-Leu-l-Leu-Aib-(d-Leu-d-Leu-Aib)2-l-Leu-l-Leu-Aib-OMe (6), that contain equal amounts of l-Leu, d-Leu, and achiral Aib residues. The conformations of peptides 5 and 6 in the crystalline state were studied using X ray crystallographic analysis. Peptide 5 formed a left-handed (M) alpha-helical structure, whereas peptide 6 was composed of a combination of fused (M) alpha helical and right-handed (P) 310-helical structures. In solution, roughly equivalent amounts of (P) and (M) helices were present in 5, whereas the (M) alpha-helix was present in 6 as its dominant conformation. PMID- 26274391 TI - The Molecular Mechanism of the Catalase-like Activity in Horseradish Peroxidase. AB - Horseradish peroxidase (HRP) is one of the most relevant peroxidase enzymes, used extensively in immunochemistry and biocatalysis applications. Unlike the closely related catalase enzymes, it exhibits a low activity to disproportionate hydrogen peroxide (H2O2). The origin of this disparity remains unknown due to the lack of atomistic information on the catalase-like reaction in HRP. Using QM(DFT)/MM metadynamics simulations, we uncover the mechanism for reduction of the HRP Compound I intermediate by H2O2 at atomic detail. The reaction begins with a hydrogen atom transfer, forming a peroxyl radical and a Compound II-like species. Reorientation of the peroxyl radical in the active site, concomitant with the transfer of the second hydrogen atom, is the rate-limiting step, with a computed free energy barrier (18.7 kcal/mol, ~ 6 kcal/mol higher than the one obtained for catalase) in good agreement with experiments. Our simulations reveal the crucial role played by the distal pocket residues in accommodating H2O2, enabling formation of a Compound II-like intermediate, similar to catalases. However, out of the two pathways for Compound II reduction found in catalases, only one is operative in HRP. Moreover, the hydrogen bond network in the distal side of HRP compensates less efficiently than in catalases for the energetic cost required to reorient the peroxyl radical at the rate-determining step. The distal Arg and a water molecule in the "wet" active site of HRP have a substantial impact on the reaction barrier, compared to the "dry" active site in catalase. Therefore, the lower catalase-like efficiency of heme peroxidases compared to catalases can be directly attributed to the different distal pocket architecture, providing hints to engineer peroxidases with a higher rate of H2O2 disproportionation. PMID- 26274392 TI - Angiopoietin-2 as a Prognostic Biomarker of Major Adverse Cardiovascular Events and All-Cause Mortality in Chronic Kidney Disease. AB - BACKGROUND: Chronic kidney disease (CKD) patients have higher prevalence of major adverse cardiovascular events (MACE) and all-cause mortality. Endothelial damage and dysfunction have been regarded as early portents of MACE in CKD patients. Angiopoietin-2 (Ang-2) impairs endothelial function and promotes aberrant neovascularization. The aim of the study was to assess the relationship between circulating Ang-2 and MACE or all-cause mortality in a CKD cohort. METHODS: A total of 621 pre-dialysis stage 3-5 CKD patients were enrolled from January 2006 to December 2011 and were followed up till October 2014. Plasma Ang-2 was measured in duplicate using commercial enzyme-linked immunosorbent assays (ELISA). Clinical outcomes included MACE or all-cause mortality. RESULTS: Of all patients, 122 (19.8%) reached MACE or all-cause mortality. Seventy-two had MACE, 79 died, and 29 had both MACE and all-cause mortality during the follow-up period of 41.5+/-28.3 months. Ang-2 quintile was divided at 1405.0, 1730.0, 2160.9, and 2829.9 pg/ml. The adjusted HR of MACE or all-cause mortality for every single higher log Ang-2 was 5.69 (95% CI: 2.00-16.20, P = 0.001). The adjusted HR of MACE or all-cause mortality was 2.48 (95% CI: 1.25-4.90) for patients of quintile 5 compared with those of quintile 1. A longitudinal association between MACE or all-cause mortality and stepwise increases in Ang-2 levels was found (P-trend = 0.008). CONCLUSIONS: Ang-2 is an independent predictor of MACE or all-cause mortality in CKD patients. Additional study is necessary in order to explore the mechanism of the association of Ang-2 with adverse outcomes in patients with CKD. PMID- 26274393 TI - Risk of Severe Acute Exacerbation of Chronic HBV Infection Cancer Patients Who Underwent Chemotherapy and Did Not Receive Anti-Viral Prophylaxis. AB - BACKGROUND: Reactivation of HBV replication with an increase in serum HBV DNA and alanine aminotransferase (ALT) activity has been reported in 20-50% of hepatitis B carriers undergoing cytotoxic chemotherapy for cancer treatment. Manifestation of HBV reactivation ranges from asymptomatic self-limiting hepatitis to severe progressive hepatic failure and fatal consequences. AIM: To investigate the risk of severe acute exacerbation of chronic HBV infection in HBsAg-positive cancer patients with solid tumors or hematological malignancies who underwent chemotherapy without antiviral prophylaxis. METHODS: A retrospective review of charts was conducted for HBsAg-positive cancer patients in our institution who underwent chemotherapy and did not receive anti-viral prophylaxis between the periods of July 2007 to January 2013. We investigate the incidence of severe acute exacerbation of chronic HBV infection if these patients with a variety of solid tumors and hematological malignancies. RESULTS: A total of 156 patients (hematological malignancies: 16; solid tumors: 140) were included. The incidence of severe acute HBV exacerbation in the patients with hematological malignancy was higher than that in solid tumors (25.0% [4/16] vs 4.3% [6/140]); P = 0.005). Additionally, patients receiving rituximab-based chemotherapy had higher acute exacerbation rate than those with non-rituximab-based chemotherapy (40.0% vs 4.1%, P = 0.001). Among the patients with solid tumors, the incidences of severe acute exacerbation of chronic HBV in hepatocellular carcinoma, colorectal cancer, lung cancer, breast cancer, gynecological cancer, urological tract cancer, head/neck cancer and other solid malignancies were 2.3%, 4.0%, 7.1%, 9.0%, 16.7%, 6.7%, 0% and 0%, respectively. CONCLUSION: Severe acute exacerbation of chronic HBV infection may occur in HBsAg-positive patients with a variety of solid tumors who received chemotherapy without adequate anti-viral prophylaxis. Hematological malignancy and rituximab-based chemotherapy are the risk factors related to severe acute exacerbation of chronic HBV infection in HBsAg-positive cancer patients undergoing chemotherapy. PMID- 26274394 TI - Role of sph2 Gene Regulation in Hemolytic and Sphingomyelinase Activities Produced by Leptospira interrogans. AB - Pathogenic members of the genus Leptospira are the causative agents of leptospirosis, a neglected disease of public and veterinary health concern. Leptospirosis is a systemic disease that in its severest forms leads to renal insufficiency, hepatic dysfunction, and pulmonary failure. Many strains of Leptospira produce hemolytic and sphingomyelinase activities, and a number of candidate leptospiral hemolysins have been identified based on sequence similarity to well-characterized bacterial hemolysins. Five of the putative hemolysins are sphingomyelinase paralogs. Although recombinant forms of the sphingomyelinase Sph2 and other hemolysins lyse erythrocytes, none have been demonstrated to contribute to the hemolytic activity secreted by leptospiral cells. In this study, we examined the regulation of sph2 and its relationship to hemolytic and sphingomyelinase activities produced by several L. interrogans strains cultivated under the osmotic conditions found in the mammalian host. The sph2 gene was poorly expressed when the Fiocruz L1-130 (serovar Copenhageni), 56601 (sv. Lai), and L495 (sv. Manilae) strains were cultivated in the standard culture medium EMJH. Raising EMJH osmolarity to physiological levels with sodium chloride enhanced Sph2 production in all three strains. In addition, the Pomona subtype kennewicki strain LC82-25 produced substantially greater amounts of Sph2 during standard EMJH growth than the other strains, and sph2 expression increased further by addition of salt. When 10% rat serum was present in EMJH along with the sodium chloride supplement, Sph2 production increased further in all strains. Osmotic regulation and differences in basal Sph2 production in the Manilae L495 and Pomona strains correlated with the levels of secreted hemolysin and sphingomyelinase activities. Finally, a transposon insertion in sph2 dramatically reduced hemolytic and sphingomyelinase activities during incubation of L. interrogans at physiologic osmolarity. Complementation of the mutation with the sph2 gene partially restored production of hemolytic and sphingomyelinase activities. These results indicate that the sph2 gene product contributes to the hemolytic and sphingomyelinase activities secreted by L. interrogans and most likely dominates those functions under the culture condition tested. PMID- 26274397 TI - Establishing the Two-Photon Linkage Isomerization Mechanism in the Nitrosyl Complex trans-[RuCl(NO)(py)4](2+) by DFT and TDDFT. AB - The density functional theory calculations presented in this work allow the first rationalization of the full linkage photoisomerization mechanism of trans [RuCl(NO)(py)4](2+), in both the forward and reverse directions. These mechanisms are consistent with the experimental data establishing that blue-light irradiation triggers the forward process, while red or IR photons trigger the reverse process. Characterization of the singlet and lowest triplet potential energy surfaces shows that, despite the unfavorable thermodynamic character of the forward process, the topologies of the surfaces and particularly some crucial surface crossings enable the isomerization. In the forward Ru-NO -> Ru-ON direction, a sequential two-photon absorption mechanism is unraveled that involves a sideways-bonded metastable state. In contrast, in the reverse reaction, two mechanisms are proposed involving either one or two photons. PMID- 26274396 TI - Binding Patterns of Rotavirus Genotypes P[4], P[6], and P[8] in China with Histo Blood Group Antigens. AB - Rotaviruses (RVs) are an important cause of severe gastroenteritis in children. It has been found that RV may recognize the histo-blood group antigens (HBGAs) as ligands or receptors and bind HBGAs in a type-dependent manner. In this study, we investigated the binding specificity of VP8* proteins from human rotaviruses (RV) that are prevalent in China including genotypes P[4], P[6], and P[8]. Through the saliva- and oligosaccharide-based binding assays, we found that the VP8* proteins of P[4] and P[8] RV showed similar reactivity with the Leb and H type 1 antigens, while P[6] RV weakly bound the Leb antigen. These findings may facilitate further research into RV host specificity and vaccine development. PMID- 26274395 TI - Additive Synergism between Asbestos and Smoking in Lung Cancer Risk: A Systematic Review and Meta-Analysis. AB - Smoking and asbestos exposure are important risks for lung cancer. Several epidemiological studies have linked asbestos exposure and smoking to lung cancer. To reconcile and unify these results, we conducted a systematic review and meta analysis to provide a quantitative estimate of the increased risk of lung cancer associated with asbestos exposure and cigarette smoking and to classify their interaction. Five electronic databases were searched from inception to May, 2015 for observational studies on lung cancer. All case-control (N = 10) and cohort (N = 7) studies were included in the analysis. We calculated pooled odds ratios (ORs), relative risks (RRs) and 95% confidence intervals (CIs) using a random effects model for the association of asbestos exposure and smoking with lung cancer. Lung cancer patients who were not exposed to asbestos and non-smoking (A S-) were compared with; (i) asbestos-exposed and non-smoking (A+S-), (ii) non exposure to asbestos and smoking (A-S+), and (iii) asbestos-exposed and smoking (A+S+). Our meta-analysis showed a significant difference in risk of developing lung cancer among asbestos exposed and/or smoking workers compared to controls (A S-), odds ratios for the disease (95% CI) were (i) 1.70 (A+S-, 1.31-2.21), (ii) 5.65; (A-S+, 3.38-9.42), (iii) 8.70 (A+S+, 5.8-13.10). The additive interaction index of synergy was 1.44 (95% CI = 1.26-1.77) and the multiplicative index = 0.91 (95% CI = 0.63-1.30). Corresponding values for cohort studies were 1.11 (95% CI = 1.00-1.28) and 0.51 (95% CI = 0.31-0.85). Our results point to an additive synergism for lung cancer with co-exposure of asbestos and cigarette smoking. Assessments of industrial health risks should take smoking and other airborne health risks when setting occupational asbestos exposure limits. PMID- 26274398 TI - Age influences the relation between subjective valence ratings and emotional word use during autobiographical memory retrieval. AB - Recent research reveals an age-related increase in positive autobiographical memory retrieval using a number of positivity measures, including valence ratings and positive word use. It is currently unclear whether the positivity shift in each of these measures co-occurs, or if age uniquely influences multiple components of autobiographical memory retrieval. The current study examined the correspondence between valence ratings and emotional word use in young and older adults' autobiographical memories. Positive word use in narratives was associated with valence ratings only in young adults' narratives. Older adults' narratives contained a consistent level of positive word use regardless of valence rating, suggesting that positive words and concepts may be chronically accessible to older adults during memory retrieval, regardless of subjective valence. Although a relation between negative word use in narratives and negative valence ratings was apparent in both young and older adults, it was stronger in older adults' narratives. These findings confirm that older adults do vary their word use in accordance with subjective valence, but they do so in a way that is different from young adults. The results also point to a potential dissociation between age related changes in subjective valence and in positive word use. PMID- 26274399 TI - Exposure of Asian Elephants and Other Exotic Ungulates to Schmallenberg Virus. AB - Schmallenberg virus (SBV) is an emerging Orthobunyavirus, first described in 2011 in cattle in Germany and subsequently spread throughout Europe, affecting mainly ruminant livestock through the induction of foetal malformations. To gain a better understanding of the spectrum of susceptible species and to assess the value of current SBV serological assays, screening of serum samples from exotic artiodactyls and perissodactyls collected at the Living Collections from the Zoological Society of London (Whipsnade and London Zoos) and Chester Zoo was carried out. There was compelling evidence of SBV infection in both zoological collections. The competitive ELISA has proved to be applicable for the detection of SBV in exotic Bovidae, Cervidae, Suidae, Giraffidae and most notably in endangered Asian elephants (Elephas maximus), but unreliable for the screening of Camelidae, for which the plaque reduction neutralisation test was considered the assay of choice. PMID- 26274400 TI - Intramolecular Vibrational Energy Redistribution in 2-Thiocytosine: SH Rotamerization Induced by Near-IR Selective Excitation of NH2 Stretching Overtone. AB - Near-IR-induced transformations, converting one amino-thiol conformer of 2 thiocytosine into another, were observed for monomers of the compound isolated in Ne, Ar, and N2 low-temperature matrixes. The two conformers involved in this phototransformation differ from each other by 180 degrees rotation of the SH group. To induce the conversion, conformers of 2-thiocytosine were selectively excited to the overtone (or combination) NH2 stretching vibrational states, using very narrowband (fwhm <1 MHz) near-IR light generated in a tunable diode laser. The conformational changes were monitored by IR spectroscopy. The conformational transformation observed in the current work provides a clear evidence of the vibrational energy redistribution from the initially excited NH2 moiety to the remote SH group that changes its orientation. PMID- 26274402 TI - Quantum Conditional Mutual Information, Reconstructed States, and State Redistribution. AB - We give two strengthenings of an inequality for the quantum conditional mutual information of a tripartite quantum state recently proved by Fawzi and Renner, connecting it with the ability to reconstruct the state from its bipartite reductions. Namely, we show that the conditional mutual information is an upper bound on the regularized relative entropy distance between the quantum state and its reconstructed version. It is also an upper bound for the measured relative entropy distance of the state to its reconstructed version. The main ingredient of the proof is the fact that the conditional mutual information is the optimal quantum communication rate in the task of state redistribution. PMID- 26274401 TI - Effects of Fungicide and Adjuvant Sprays on Nesting Behavior in Two Managed Solitary Bees, Osmia lignaria and Megachile rotundata. AB - There is a growing body of empirical evidence showing that wild and managed bees are negatively impacted by various pesticides that are applied in agroecosystems around the world. The lethal and sublethal effects of two widely used fungicides and one adjuvant were assessed in cage studies in California on blue orchard bees, Osmia lignaria, and in cage studies in Utah on alfalfa leafcutting bees, Megachile rotundata. The fungicides tested were Rovral 4F (iprodione) and Pristine (mixture of pyraclostrobin + boscalid), and the adjuvant tested was N 90, a non-ionic wetting agent (90% polyethoxylated nonylphenol) added to certain tank mixtures of fungicides to improve the distribution and contact of sprays to plants. In separate trials, we erected screened cages and released 20 paint marked females plus 30-50 males per cage to document the behavior of nesting bees under treated and control conditions. For all females in each cage, we recorded pollen-collecting trip times, nest substrate-collecting trip times (i.e., mud for O. lignaria and cut leaf pieces for M. rotundata), cell production rate, and the number of attempts each female made to enter her own or to enter other nest entrances upon returning from a foraging trip. No lethal effects of treatments were observed on adults, nor were there effects on time spent foraging for pollen and nest substrates and on cell production rate. However, Rovral 4F, Pristine, and N-90 disrupted the nest recognition abilities of O. lignaria females. Pristine, N-90, and Pristine + N-90 disrupted nest recognition ability of M. rotundata females. Electroantennogram responses of antennae of O. lignaria females maintained in the laboratory did not differ significantly between the fungicide-exposed and control bees. Our results provide the first empirical evidence that two commonly used fungicides and a non-ionic adjuvant can disrupt nest recognition in two managed solitary bee species. PMID- 26274403 TI - Thresholds for Correcting Errors, Erasures, and Faulty Syndrome Measurements in Degenerate Quantum Codes. AB - We suggest a technique for constructing lower (existence) bounds for the fault tolerant threshold to scalable quantum computation applicable to degenerate quantum codes with sublinear distance scaling. We give explicit analytic expressions combining probabilities of erasures, depolarizing errors, and phenomenological syndrome measurement errors for quantum low-density parity-check codes with logarithmic or larger distances. These threshold estimates are parametrically better than the existing analytical bound based on percolation. PMID- 26274404 TI - Negative Differential Conductivity in an Interacting Quantum Gas. AB - We report on the observation of negative differential conductivity (NDC) in a quantum transport device for neutral atoms employing a multimode tunneling junction. The system is realized with a Bose-Einstein condensate loaded in a one dimensional optical lattice with high site occupancy. We induce an initial difference in chemical potential at one site by local atom removal. The ensuing transport dynamics are governed by the interplay between the tunneling coupling, the interaction energy, and intrinsic collisions, which turn the coherent coupling into a hopping process. The resulting current-voltage characteristics exhibit NDC, for which we identify atom number-dependent tunneling as a new microscopic mechanism. Our study opens new ways for the future implementation and control of complex neutral atom quantum circuits. PMID- 26274405 TI - Multidimensional Langevin Modeling of Nonoverdamped Dynamics. AB - Based on a given time series, data-driven Langevin modeling aims to construct a low-dimensional dynamical model of the underlying system. When dealing with physical data as provided by, e.g., all-atom molecular dynamics simulations, effects due to small damping may be important to correctly describe the statistics (e.g., the energy landscape) and the dynamics (e.g., transition times). To include these effects in a dynamical model, an algorithm that propagates a second-order Langevin scheme is derived, which facilitates the treatment of multidimensional data. Adopting extensive molecular dynamics simulations of a peptide helix, a five-dimensional model is constructed that successfully forecasts the complex structural dynamics of the system. Neglect of small damping effects, on the other hand, is shown to lead to significant errors and inconsistencies. PMID- 26274406 TI - Krylov-Projected Quantum Monte Carlo Method. AB - We present an approach to the calculation of arbitrary spectral, thermal, and excited state properties within the full configuration interaction quzantum Monte Carlo framework. This is achieved via an unbiased projection of the Hamiltonian eigenvalue problem into a space of stochastically sampled Krylov vectors, thus, enabling the calculation of real-frequency spectral and thermal properties and avoiding explicit analytic continuation. We use this approach to calculate temperature-dependent properties and one- and two-body spectral functions for various Hubbard models, as well as isolated excited states in ab initio systems. PMID- 26274408 TI - Mass Gap for Black-Hole Formation in Higher-Derivative and Ghost-Free Gravity. AB - We study a spherical gravitational collapse of a small mass in higher-derivative and ghost-free theories of gravity. By boosting a solution of linearized equations for a static point mass in such theories we obtain in the Penrose limit the gravitational field of an ultrarelativistic particle. Taking a superposition of such solutions we construct a metric of a collapsing null shell in the linearized higher-derivative and ghost-free gravity. The latter allows one to find the gravitational field of a thick null shell. By analyzing these solutions we demonstrate that in a wide class of the higher dimensional theories of gravity as well as for the ghost-free gravity there exists a mass gap for mini-black-hole production. We also found conditions when the curvature invariants remain finite at r=0 for the collapse of the thick null shell. PMID- 26274407 TI - Binary Black Hole Mergers from Globular Clusters: Implications for Advanced LIGO. AB - The predicted rate of binary black hole mergers from galactic fields can vary over several orders of magnitude and is extremely sensitive to the assumptions of stellar evolution. But in dense stellar environments such as globular clusters, binary black holes form by well-understood gravitational interactions. In this Letter, we study the formation of black hole binaries in an extensive collection of realistic globular cluster models. By comparing these models to observed Milky Way and extragalactic globular clusters, we find that the mergers of dynamically formed binaries could be detected at a rate of ~100 per year, potentially dominating the binary black hole merger rate. We also find that a majority of cluster-formed binaries are more massive than their field-formed counterparts, suggesting that Advanced LIGO could identify certain binaries as originating from dense stellar environments. PMID- 26274410 TI - Bootstrapping the Three Dimensional Supersymmetric Ising Model. AB - We implement the conformal bootstrap program for three dimensional conformal field theories with N=2 supersymmetry and find universal constraints on the spectrum of operator dimensions in these theories. By studying the bounds on the dimension of the first scalar appearing in the operator product expansion of a chiral and an antichiral primary, we find a kink at the expected location of the critical three dimensional N=2 Wess-Zumino model, which can be thought of as a supersymmetric analog of the critical Ising model. Focusing on this kink, we determine, to high accuracy, the low-lying spectrum of operator dimensions of the theory, as well as the stress-tensor two-point function. We find that the latter is in an excellent agreement with an exact computation. PMID- 26274409 TI - Wide-Field Lensing Mass Maps from Dark Energy Survey Science Verification Data. AB - We present a mass map reconstructed from weak gravitational lensing shear measurements over 139 deg2 from the Dark Energy Survey science verification data. The mass map probes both luminous and dark matter, thus providing a tool for studying cosmology. We find good agreement between the mass map and the distribution of massive galaxy clusters identified using a red-sequence cluster finder. Potential candidates for superclusters and voids are identified using these maps. We measure the cross-correlation between the mass map and a magnitude limited foreground galaxy sample and find a detection at the 6.8sigma level with 20 arc min smoothing. These measurements are consistent with simulated galaxy catalogs based on N-body simulations from a cold dark matter model with a cosmological constant. This suggests low systematics uncertainties in the map. We summarize our key findings in this Letter; the detailed methodology and tests for systematics are presented in a companion paper. PMID- 26274412 TI - Resolving the Tevatron Top Quark Forward-Backward Asymmetry Puzzle: Fully Differential Next-to-Next-to-Leading-Order Calculation. AB - We determine the dominant missing standard model (SM) contribution to the top quark pair forward-backward asymmetry at the Tevatron. Contrary to past expectations, we find a large, around 27%, shift relative to the well-known value of the inclusive asymmetry in next-to-leading order QCD. Combining all known standard model corrections, we find that A(FB)(SM)=0.095+/-0.007. This value is in agreement with the latest DO measurement [V. M. Abazov et al. (D0 Collaboration), Phys. Rev. D 90, 072011 (2014)] A(FB)(D?)=0.106+/-0.03 and about 1.5sigma below that of CDF [T. Aaltonen et al. (CDF Collaboration), Phys. Rev. D 87, 092002 (2013)] A(FB)(CDF)=0.164+/-0.047. Our result is derived from a fully differential calculation of the next-to-next-to leading order (NNLO) QCD corrections to inclusive top pair production at hadron colliders and includes without any approximation-all partonic channels contributing to this process. This is the first complete fully differential calculation in NNLO QCD of a two-to two scattering process with all colored partons. PMID- 26274413 TI - Neutron Resonance Widths and the Porter-Thomas Distribution. AB - Experimental evidence has recently put the validity of the Porter-Thomas distribution (PTD) for partial neutron widths into question. We identify two terms in the effective Hamiltonian that violate orthogonal invariance (the basis for the PTD). Both are due to the coupling to the decay channels. We show that realistic estimates for the coupling to the neutron channel and for nonstatistical gamma decays yield significant modifications of the PTD, similar to the observed ones. PMID- 26274414 TI - 23Na(alpha,p)26Mg Reaction Rate at Astrophysically Relevant Energies. AB - The production of 26Al in massive stars is sensitive to the 23Na(alpha,p)26Mg cross section. Recent experimental data suggest the currently recommended cross sections are underestimated by a factor of ~40. We present here differential cross sections for the 23Na(alpha,p)26Mg reaction measured in the energy range E(c.m.)=1.7-2.5 MeV. Concurrent measurements of Rutherford scattering provide absolute normalizations that are independent of variations in target properties. Angular distributions are measured for both p0 and p1 permitting the determination of total cross sections. The results show no significant deviation from the statistical model calculations upon which the recommended rates are based. We therefore retain the previous recommendation without the increase in cross section and resulting stellar reaction rates by a factor of 40, impacting the 26Al yield from massive stars by more than a factor of 3. PMID- 26274415 TI - Measurement of 23Na(alpha,p)26Mg at Energies Relevant to 26Al Production in Massive Stars. AB - 26Al is an important radioisotope in astrophysics that provides evidence of ongoing nucleosynthesis in the Galaxy. The 23Na(alpha, p)26Mg reaction has been identified by a sensitivity study as being one of the most important reactions for the production of 26Al in the convective C/Ne burning shell of massive stars. Owing to large uncertainties in previous experimental data, model calculations are used for the reaction rate of 23Na(alpha, p)26Mg in this sensitivity study. Current experimental data suggest a reaction rate a factor of ~40 higher than model calculations. However, a new measurement of this reaction cross section has been made in inverse kinematics in the energy range E(c.m.)=1.28-3.15 MeV at TRIUMF, and found to be in reasonable agreement with the model calculation. A new reaction rate is calculated and tight constraints on the uncertainty in the production of 26Al, due to this reaction, are determined. PMID- 26274416 TI - Control of Optical Transitions with Magnetic Fields in Weakly Bound Molecules. AB - In weakly bound diatomic molecules, energy levels are closely spaced and thus more susceptible to mixing by magnetic fields than in the constituent atoms. We use this effect to control the strengths of forbidden optical transitions in (88)Sr2 over 5 orders of magnitude with modest fields by taking advantage of the intercombination-line threshold. The physics behind this remarkable tunability is accurately explained with both a simple model and quantum chemistry calculations, and suggests new possibilities for molecular clocks. We show how mixed quantization in an optical lattice can simplify molecular spectroscopy. Furthermore, our observation of formerly inaccessible f-parity excited states offers an avenue for improving theoretical models of divalent-atom dimers. PMID- 26274417 TI - Anyon Hubbard Model in One-Dimensional Optical Lattices. AB - Raman-assisted hopping may be used to realize the anyon Hubbard model in one dimensional optical lattices. We propose a feasible scenario that significantly improves the proposal of T. Keilmann et al. [Nat. Commun. 2, 361 (2011)], allowing as well for an exact realization of the two-body hard-core constraint, and for controllable effective interactions without the need of Feshbach resonances. We show that the combination of anyonic statistics and two-body hard core constraint leads to a rich ground-state physics, including Mott insulators with attractive interactions, pair superfluids, dimer phases, and multicritical points. Moreover, the anyonic statistics results in a novel two-component superfluid of holon and doublon dimers, characterized by a large but finite compressibility and a multipeaked momentum distribution, which may be easily revealed experimentally. PMID- 26274418 TI - Precision Isotope Shift Measurements in Calcium Ions Using Quantum Logic Detection Schemes. AB - We demonstrate an efficient high-precision optical spectroscopy technique for single trapped ions with nonclosed transitions. In a double-shelving technique, the absorption of a single photon is first amplified to several phonons of a normal motional mode shared with a cotrapped cooling ion of a different species, before being further amplified to thousands of fluorescence photons emitted by the cooling ion using the standard electron shelving technique. We employ this extension of the photon recoil spectroscopy technique to perform the first high precision absolute frequency measurement of the 2D(3/2)->2P(1/2) transition in calcium, resulting in a transition frequency of f=346 000 234 867(96) kHz. Furthermore, we determine the isotope shift of this transition and the 2S(1/2) >2P(1/2) transition for 42Ca+, 44Ca+, and 48Ca+ ions relative to 40Ca+ with an accuracy below 100 kHz. Improved field and mass shift constants of these transitions as well as changes in mean square nuclear charge radii are extracted from this high resolution data. PMID- 26274419 TI - Experimental Phase-Space Tomography of Semiconductor Laser Dynamics. AB - We perform phase-space tomography of semiconductor laser dynamics by simultaneous experimental determination of optical intensity, frequency, and population inversion with high temporal resolution. We apply this technique to a laser with delayed feedback, serving as prominent example for high-dimensional chaotic dynamics and as model system for fundamental investigations of complex systems. Our approach allows us to explore so far unidentified trajectories in phase space and identify the underlying physical mechanism. PMID- 26274420 TI - Transient Uncoupling Induces Synchronization. AB - Finding conditions that support synchronization is a fertile and active area of research with applications across multiple disciplines. Here we present and analyze a scheme for synchronizing chaotic dynamical systems by transiently uncoupling them. Specifically, systems coupled only in a fraction of their state space may synchronize even if fully coupled they do not. While for many standard systems coupling strengths need to be bounded to ensure synchrony, transient uncoupling removes this bound and thus enables synchronization in an infinite range of effective coupling strengths. The presented coupling scheme therefore opens up the possibility to induce synchrony in (biological or technical) systems whose parameters are fixed and cannot be modified continuously. PMID- 26274421 TI - Nonlinear Hysteretic Torsional Waves. AB - We theoretically study and experimentally report the propagation of nonlinear hysteretic torsional pulses in a vertical granular chain made of cm-scale, self hanged magnetic beads. As predicted by contact mechanics, the torsional coupling between two beads is found to be nonlinear hysteretic. This results in a nonlinear pulse distortion essentially different from the distortion predicted by classical nonlinearities and in a complex dynamic response depending on the history of the wave particle angular velocity. Both are consistent with the predictions of purely hysteretic nonlinear elasticity and the Preisach-Mayergoyz hysteresis model, providing the opportunity to study the phenomenon of nonlinear dynamic hysteresis in the absence of other types of material nonlinearities. The proposed configuration reveals a plethora of interesting phenomena including giant amplitude-dependent attenuation, short-term memory, as well as dispersive properties. Thus, it could find interesting applications in nonlinear wave control devices such as strong amplitude-dependent filters. PMID- 26274422 TI - Self-Consistent Simulation of Transport and Energy Deposition of Intense Laser Accelerated Proton Beams in Solid-Density Matter. AB - The first self-consistent hybrid particle-in-cell (PIC) simulation of intense proton beam transport and energy deposition in solid-density matter is presented. Both the individual proton slowing-down and the collective beam-plasma interaction effects are taken into account with a new dynamic proton stopping power module that has been added to a hybrid PIC code. In this module, the target local stopping power can be updated at each time step based on its thermodynamic state. For intense proton beams, the reduction of target stopping power from the cold condition due to continuous proton heating eventually leads to broadening of the particle range and energy deposition far beyond the Bragg peak. For tightly focused beams, large magnetic field growth in collective interactions results in self-focusing of the beam and much stronger localized heating of the target. PMID- 26274423 TI - Temporal Narrowing of Neutrons Produced by High-Intensity Short-Pulse Lasers. AB - The production of neutron beams having short temporal duration is studied using ultraintense laser pulses. Laser-accelerated protons are spectrally filtered using a laser-triggered microlens to produce a short duration neutron pulse via nuclear reactions induced in a converter material (LiF). This produces a ~3 ns duration neutron pulse with 10(4) n/MeV/sr/shot at 0.56 m from the laser irradiated proton source. The large spatial separation between the neutron production and the proton source allows for shielding from the copious and undesirable radiation resulting from the laser-plasma interaction. This neutron pulse compares favorably to the duration of conventional accelerator sources and should scale up with, present and future, higher energy laser facilities to produce brighter and shorter neutron beams for ultrafast probing of dense materials. PMID- 26274425 TI - Direct Observation of the Injection Dynamics of a Laser Wakefield Accelerator Using Few-Femtosecond Shadowgraphy. AB - We present few-femtosecond shadowgraphic snapshots taken during the nonlinear evolution of the plasma wave in a laser wakefield accelerator with transverse synchronized few-cycle probe pulses. These snapshots can be directly associated with the electron density distribution within the plasma wave and give quantitative information about its size and shape. Our results show that self injection of electrons into the first plasma-wave period is induced by a lengthening of the first plasma period. Three-dimensional particle-in-cell simulations support our observations. PMID- 26274424 TI - Demonstration of High Performance in Layered Deuterium-Tritium Capsule Implosions in Uranium Hohlraums at the National Ignition Facility. AB - We report on the first layered deuterium-tritium (DT) capsule implosions indirectly driven by a "high-foot" laser pulse that were fielded in depleted uranium hohlraums at the National Ignition Facility. Recently, high-foot implosions have demonstrated improved resistance to ablation-front Rayleigh Taylor instability induced mixing of ablator material into the DT hot spot [Hurricane et al., Nature (London) 506, 343 (2014)]. Uranium hohlraums provide a higher albedo and thus an increased drive equivalent to an additional 25 TW laser power at the peak of the drive compared to standard gold hohlraums leading to higher implosion velocity. Additionally, we observe an improved hot-spot shape closer to round which indicates enhanced drive from the waist. In contrast to findings in the National Ignition Campaign, now all of our highest performing experiments have been done in uranium hohlraums and achieved total yields approaching 10^{16} neutrons where more than 50% of the yield was due to additional heating of alpha particles stopping in the DT fuel. PMID- 26274426 TI - Multibeam Stimulated Raman Scattering in Inertial Confinement Fusion Conditions. AB - Stimulated Raman scattering from multiple laser beams arranged in a cone sharing a common daughter wave is investigated for inertial confinement fusion (ICF) conditions in a inhomogeneous plasma. It is found that the shared electron plasma wave (EPW) process, where the lasers collectively drive the same EPW, can lead to an absolute instability when the electron density reaches a matching condition dependent on the cone angle of the laser beams. This mechanism could explain recent experimental observations of hot electrons at early times in ICF experiments, at densities well below quarter critical when two plasmon decay is not expected to occur. PMID- 26274427 TI - Formation of Ultrarelativistic Electron Rings from a Laser-Wakefield Accelerator. AB - Ultrarelativistic-energy electron ring structures have been observed from laser wakefield acceleration experiments in the blowout regime. These electron rings had 170-280 MeV energies with 5%-25% energy spread and ~10 pC of charge and were observed over a range of plasma densities and compositions. Three-dimensional particle-in-cell simulations show that laser intensity enhancement in the wake leads to sheath splitting and the formation of a hollow toroidal pocket in the electron density around the wake behind the first wake period. If the laser propagates over a distance greater than the ideal dephasing length, some of the dephasing electrons in the second period can become trapped within the pocket and form an ultrarelativistic electron ring that propagates in free space over a meter-scale distance upon exiting the plasma. Such a structure acts as a relativistic potential well, which has applications for accelerating positively charged particles such as positrons. PMID- 26274428 TI - Avalanches in Wood Compression. AB - Wood is a multiscale material exhibiting a complex viscoplastic response. We study avalanches in small wood samples in compression. "Woodquakes" measured by acoustic emission are surprisingly similar to earthquakes and crackling noise in rocks and laboratory tests on brittle materials. Both the distributions of event energies and of waiting (silent) times follow power laws. The stress-strain response exhibits clear signatures of localization of deformation to "weak spots" or softwood layers, as identified using digital image correlation. Even though material structure-dependent localization takes place, the avalanche behavior remains scale-free. PMID- 26274429 TI - One Hole in the Two-Leg t-J Ladder and Adiabatic Continuity to the Noninteracting Limit. AB - We carry out density-matrix-renormalization group (DMRG) calculations for the problem of one doped hole in a two-leg t-J ladder. Recent studies have concluded that exotic "Mott" physics-arising from the projection onto the space of no double-occupied sites-is manifest in this model system, leading to charge localization and a new mechanism for charge modulation. In contrast, we show that there is no localization and that the charge-density modulation arises when the minimum in the quasiparticle dispersion moves away from pi. Although singular changes in the quasiparticle dispersion do occur as a function of model parameters, all of the DMRG results can be qualitatively understood from a noninteracting "band-structure" perspective. PMID- 26274431 TI - Interfacial Structure Dependent Spin Mixing Conductance in Cobalt Thin Films. AB - Enhancement of Gilbert damping in polycrystalline cobalt thin-film multilayers of various thicknesses, overlayered with copper or iridium, was studied in order to understand the role of local interface structure in spin pumping. X-ray diffraction indicates that cobalt films less than 6 nm thick have strong fcc(111) texture while thicker films are dominated by hcp(0001) structure. The intrinsic damping for cobalt thicknesses above 6 nm is weakly dependent on cobalt thickness for both overlayer materials, and below 6 nm the iridium overlayers show higher damping enhancement compared to copper overlayers, as expected due to spin pumping. The interfacial spin mixing conductance is significantly enhanced in structures where both cobalt and iridium have fcc(111) structure in comparison to those where the cobalt layer has subtly different hcp(0001) texture at the interface. PMID- 26274430 TI - Magnetic Field-Induced Insulator-Semimetal Transition in a Pyrochlore Nd2Ir2O7. AB - We investigate magnetotransport properties in a single crystal of pyrochore-type Nd2Ir2O7. The metallic conduction is observed on the antiferromagnetic domain walls of the all-in-all-out-type Ir 5d moment ordered insulating bulk state that can be finely controlled by an external magnetic field along [111]. On the other hand, an applied field along [001] induces the bulk phase transition from insulator to semimetal as a consequence of the field-induced modification of the Nd 4f and Ir 5d moment configurations. A theoretical calculation consistently describing the experimentally observed features suggests a variety of exotic topological states as functions of electron correlation and Ir 5d moment orders, which can be finely tuned by the choice of rare-earth ion and magnetic field, respectively. PMID- 26274432 TI - Tunneling Anomalous and Spin Hall Effects. AB - We predict, theoretically, the existence of the anomalous Hall effect when a tunneling current flows through a tunnel junction in which only one of the electrodes is magnetic. The interfacial spin-orbit coupling present in the barrier region induces a spin-dependent momentum filtering in the directions perpendicular to the tunneling current, resulting in a skew tunneling even in the absence of impurities. This produces an anomalous Hall conductance and spin Hall currents in the nonmagnetic electrode when a bias voltage is applied across the tunneling heterojunction. If the barrier is composed of a noncentrosymmetric material, the anomalous Hall conductance and spin Hall currents become anisotropic with respect to both the magnetization and crystallographic directions, allowing us to separate this interfacial phenomenon from the bulk anomalous and spin Hall contributions. The proposed effect should be useful for proving and quantifying the interfacial spin-orbit fields in metallic and metal semiconductor systems. PMID- 26274433 TI - Violation of the Wiedemann-Franz Law in Hydrodynamic Electron Liquids. AB - The Wiedemann-Franz law, connecting the electronic thermal conductivity to the electrical conductivity of a disordered metal, is generally found to be well satisfied even when electron-electron (e-e) interactions are strong. In ultraclean conductors in the hydrodynamic regime, however, large deviations from the standard form of the law are expected, due to the fact that e-e interactions affect the two conductivities in radically different ways. Thus, the standard Wiedemann-Franz ratio between the thermal and the electric conductivity is reduced by a factor 1+tau/tau(th)(ee), where 1/tau is the momentum relaxation rate and tau(th)(ee) is the relaxation time of the thermal current due to e-e collisions. Here we study the density and temperature dependence of 1/tau(th)(ee) of two-dimensional electron liquids. We show that at low temperature 1/tau(th)(ee) is 8/5 of the quasiparticle decay rate; remarkably, the same result is found in doped graphene and in conventional electron liquids in parabolic bands. PMID- 26274434 TI - Time-Dependent Thermal Transport Theory. AB - Understanding thermal transport in nanoscale systems presents important challenges to both theory and experiment. In particular, the concept of local temperature at the nanoscale appears difficult to justify. Here, we propose a theoretical approach where we replace the temperature gradient with controllable external blackbody radiations. The theory recovers known physical results, for example, the linear relation between the thermal current and the temperature difference of two blackbodies. Furthermore, our theory is not limited to the linear regime and goes beyond accounting for nonlinear effects and transient phenomena. Since the present theory is general and can be adapted to describe both electron and phonon dynamics, it provides a first step toward a unified formalism for investigating thermal and electronic transport. PMID- 26274435 TI - High Temperature Magnetic Stabilization of Cobalt Nanoparticles by an Antiferromagnetic Proximity Effect. AB - Thermal activation tends to destroy the magnetic stability of small magnetic nanoparticles, with crucial implications for ultrahigh density recording among other applications. Here we demonstrate that low-blocking-temperature ferromagnetic (FM) Co nanoparticles (T(B)<70 K) become magnetically stable above 400 K when embedded in a high-Neel-temperature antiferromagnetic (AFM) NiO matrix. The origin of this remarkable T(B) enhancement is due to a magnetic proximity effect between a thin CoO shell (with low Neel temperature, T(N), and high anisotropy, K(AFM)) surrounding the Co nanoparticles and the NiO matrix (with high T(N) but low K(AFM)). This proximity effect yields an effective antiferromagnet with an apparent T(N) beyond that of bulk CoO, and an enhanced anisotropy compared to NiO. In turn, the Co core FM moment is stabilized against thermal fluctuations via core-shell exchange-bias coupling, leading to the observed T(B) increase. Mean-field calculations provide a semiquantitative understanding of this magnetic-proximity stabilization mechanism. PMID- 26274436 TI - Drastic Pressure Effect on the Extremely Large Magnetoresistance in WTe2: Quantum Oscillation Study. AB - The quantum oscillations of the magnetoresistance under ambient and high pressure have been studied for WTe2 single crystals, in which extremely large magnetoresistance was discovered recently. By analyzing the Shubnikov-de Haas oscillations, four Fermi surfaces are identified, and two of them are found to persist to high pressure. The sizes of these two pockets are comparable, but show increasing difference with pressure. At 0.3 K and in 14.5 T, the magnetoresistance decreases drastically from 1.25*10(5)% under ambient pressure to 7.47*10(3)% under 23.6 kbar, which is likely caused by the relative change of Fermi surfaces. These results support the scenario that the perfect balance between the electron and hole populations is the origin of the extremely large magnetoresistance in WTe2. PMID- 26274437 TI - Ab Initio Construction of Magnetic Phase Diagrams in Alloys: The Case of Fe(1 x)Mn(x)Pt. AB - A first-principles approach to the construction of concentration-temperature magnetic phase diagrams of metallic alloys is presented. The method employs self consistent total energy calculations based on the coherent potential approximation for partially ordered and noncollinear magnetic states and is able to account for competing interactions and multiple magnetic phases. Application to the Fe(1-x)Mn(x)Pt "magnetic chameleon" system yields the sequence of magnetic phases at T=0 and the c-T magnetic phase diagram in good agreement with experiment, and a new low-temperature phase is predicted at the Mn-rich end. The importance of non-Heisenberg interactions for the description of the magnetic phase diagram is demonstrated. PMID- 26274438 TI - Electric-Field Modulation of Damping Constant in a Ferromagnetic Semiconductor (Ga,Mn)As. AB - The modulation of the Gilbert damping constant alpha in (Ga,Mn)As by the application of an electric field is detected by ferromagnetic resonance measurements, where alpha increases with decreasing hole concentration. The smaller modulation of other magnetic parameters, such as magnetic anisotropy fields and Lande g factor, suggests that the modulation of alpha is governed by other effects rather than the spin-orbit coupling. Comparison of the conductivity dependence of alpha with that of the magnetization indicates that the magnetic disorder induced by carrier localization plays a major role in determining the magnitude of alpha in (Ga,Mn)As. PMID- 26274439 TI - Phonon-Modulated Magnetic Interactions and Spin Tomonaga-Luttinger Liquid in the p-Orbital Antiferromagnet CsO2. AB - The magnetic response of antiferromagnetic CsO2, coming from the p-orbital S=1/2 spins of anionic O2(-) molecules, is followed by 133Cs nuclear magnetic resonance across the structural phase transition occurring at T(s1)=61 K on cooling. Above T(s1), where spins form a square magnetic lattice, we observe a huge, nonmonotonic temperature dependence of the exchange coupling originating from thermal librations of O2(-) molecules. Below T(s1), where antiferromagnetic spin chains are formed as a result of p-orbital ordering, we observe a spin Tomonaga Luttinger-liquid behavior of spin dynamics. These two interesting phenomena, which provide rare simple manifestations of the coupling between spin, lattice, and orbital degrees of freedom, establish CsO2 as a model system for molecular solids. PMID- 26274441 TI - One-Dimensional Chirality: Strong Optical Activity in Epsilon-Near-Zero Metamaterials. AB - We suggest that electromagnetic chirality, generally displayed by 3D or 2D complex chiral structures, can occur in 1D patterned composites whose components are achiral. This feature is highly unexpected in a 1D system which is geometrically achiral since its mirror image can always be superposed onto it by a 180 deg rotation. We analytically evaluate from first principles the bianisotropic response of multilayered metamaterials and we show that the chiral tensor is not vanishing if the system is geometrically one-dimensional chiral; i.e., its mirror image cannot be superposed onto it by using translations without resorting to rotations. As a signature of 1D chirality, we show that 1D chiral metamaterials support optical activity and we prove that this phenomenon undergoes a dramatic nonresonant enhancement in the epsilon-near-zero regime where the magnetoelectric coupling can become dominant in the constitutive relations. PMID- 26274440 TI - Zero-Field Dissipationless Chiral Edge Transport and the Nature of Dissipation in the Quantum Anomalous Hall State. AB - The quantum anomalous Hall (QAH) effect is predicted to possess, at a zero magnetic field, chiral edge channels that conduct a spin polarized current without dissipation. While edge channels have been observed in previous experimental studies of the QAH effect, their dissipationless nature at a zero magnetic field has not been convincingly demonstrated. By a comprehensive experimental study of the gate and temperature dependences of local and nonlocal magnetoresistance, we unambiguously establish the dissipationless edge transport. By studying the onset of dissipation, we also identify the origin of dissipative channels and clarify the surprising observation that the critical temperature of the QAH effect is 2 orders of magnitude smaller than the Curie temperature of ferromagnetism. PMID- 26274442 TI - Interaction of Strain and Nuclear Spins in Silicon: Quadrupolar Effects on Ionized Donors. AB - The nuclear spins of ionized donors in silicon have become an interesting quantum resource due to their very long coherence times. Their perfect isolation, however, comes at a price, since the absence of the donor electron makes the nuclear spin difficult to control. We demonstrate that the quadrupolar interaction allows us to effectively tune the nuclear magnetic resonance of ionized arsenic donors in silicon via strain and determine the two nonzero elements of the S tensor linking strain and electric field gradients in this material to S(11)=1.5*10(22) V/m2 and S(44)=6*10(22) V/m2. We find a stronger benefit of dynamical decoupling on the coherence properties of transitions subject to first-order quadrupole shifts than on those subject to only second order shifts and discuss applications of quadrupole physics including mechanical driving of magnetic resonance, cooling of mechanical resonators, and strain mediated spin coupling. PMID- 26274443 TI - Statistical Physics of Viral Capsids with Broken Symmetry. AB - We present a model to understand quantitatively the role of symmetry breaking in assembly of macromolecular aggregates in general, and the protein shells of viruses in particular. A simple dodecahedral lattice model with a quadrupolar order parameter allows us to demonstrate how symmetry breaking may reduce the probability of assembly errors and, consequently, enhance assembly efficiency. We show that the ground state is characterized by large-scale cooperative zero energy modes. In analogy with other models, this suggests a general physical principle: the tendency of biological molecules to generate symmetric structures competes with the tendency to break symmetry in order to achieve specific functional goals. PMID- 26274444 TI - Emergence of Collective Motion in a Model of Interacting Brownian Particles. AB - By studying a system of Brownian particles that interact among themselves only through a local velocity-alignment force that does not affect their speed, we show that self-propulsion is not a necessary feature for the flocking transition to take place as long as underdamped particle dynamics can be guaranteed. Moreover, the system transits from stationary phases close to thermal equilibrium, with no net flux of particles, to far-from-equilibrium ones exhibiting collective motion, phase coexistence, long-range order, and giant number fluctuations, features typically associated with ordered phases of models where self-propelled particles with overdamped dynamics are considered. PMID- 26274411 TI - Observation of the B(s)(0)->eta'eta' Decay. AB - The first observation of the B(s)(0)->eta'eta' decay is reported. The study is based on a sample of proton-proton collisions corresponding to 3.0 fb(-1) of integrated luminosity collected with the LHCb detector. The significance of the signal is 6.4 standard deviations. The branching fraction is measured to be [3.31+/-0.64(stat)+/-0.28(syst)+/-0.12(norm)]*10(-5), where the third uncertainty comes from the B(+/-)->eta'K(+/-) branching fraction that is used as a normalization. In addition, the charge asymmetries of B(+/-)->eta'K(+/-) and B(+/ )->phiK(+/-), which are control channels, are measured to be (-0.2+/-1.3)% and (+1.7+/-1.3)%, respectively. All results are consistent with theoretical expectations. PMID- 26274445 TI - Mosaic Attenuation: Etiology, Methods of Differentiation, and Pitfalls. AB - Mosaic attenuation is a commonly encountered pattern on computed tomography that is defined as heterogeneous areas of differing lung attenuation. This heterogeneous pattern of attenuation is the result of diverse causes that include diseases of the small airways, pulmonary vasculature, alveoli, and interstitium, alone or in combination. Small airways disease can be a primary disorder, such as respiratory bronchiolitis or constrictive bronchiolitis, or be part of parenchymal lung disease, such as hypersensitivity pneumonitis, or large airways disease, such as bronchiectasis and asthma. Vascular causes resulting in mosaic attenuation are typically chronic thromboembolic pulmonary hypertension, which is characterized by organizing thrombi in the elastic pulmonary arteries, or pulmonary arterial hypertension, a heterogeneous group of diseases affecting the distal pulmonary arterioles. Diffuse ground-glass opacity can result in a mosaic pattern related to a number of processes in acute (eg, infection, pulmonary edema), subacute (eg, organizing pneumonia), or chronic (eg, fibrotic diseases) settings. Imaging clues that can assist the radiologist in pinpointing a diagnosis include evidence of large airway involvement, cardiovascular abnormalities, septal thickening, signs of fibrosis, and demonstration of airtrapping at expiratory imaging. PMID- 26274447 TI - Topography-Correlated Confocal Raman Microscopy with Cylindrical Vector Beams for Probing Nanoscale Structural Order. AB - Cylindrical vector beams, such as radially or azimuthally polarized doughnut beams, are combined with topography studies of pentacene thin films, allowing us to correlate Raman spectroscopy with intermolecular interactions depending on the particular pentacene polymorph. Polarization-dependent Raman spectra of the C-H bending vibrations are resolved layer by layer within a thin film of ~20 nm thickness. The variation of the Raman peak positions indicates changes in the molecular orientation and in the local environment at different heights of the pentacene film. With the assistance of a theoretical model based on harmonic oscillator and perturbation theory, our method reveals the local structural order and the polymorph at different locations within the same pentacene thin film, depending mainly on its thickness. In good agreement with the crystallographic structures reported in the literature, our observations demonstrate that the first few monolayers grown in a structure are closer to the thin-film phase, but for larger film thicknesses, the morphology evolves toward the crystal-bulk phase with a larger tilting angle of the pentacene molecules against the substrate normal. PMID- 26274448 TI - Full-Dimensional Quantum State-to-State Nonadiabatic Dynamics for Photodissociation of Ammonia in its A-Band. PMID- 26274446 TI - Cyclin G Functions as a Positive Regulator of Growth and Metabolism in Drosophila. AB - In multicellular organisms, growth and proliferation is adjusted to nutritional conditions by a complex signaling network. The Insulin receptor/target of rapamycin (InR/TOR) signaling cascade plays a pivotal role in nutrient dependent growth regulation in Drosophila and mammals alike. Here we identify Cyclin G (CycG) as a regulator of growth and metabolism in Drosophila. CycG mutants have a reduced body size and weight and show signs of starvation accompanied by a disturbed fat metabolism. InR/TOR signaling activity is impaired in cycG mutants, combined with a reduced phosphorylation status of the kinase Akt1 and the downstream factors S6-kinase and eukaryotic translation initiation factor 4E binding protein (4E-BP). Moreover, the expression and accumulation of Drosophila insulin like peptides (dILPs) is disturbed in cycG mutant brains. Using a reporter assay, we show that the activity of one of the first effectors of InR signaling, Phosphoinositide 3-kinase (PI3K92E), is unaffected in cycG mutants. However, the metabolic defects and weight loss in cycG mutants were rescued by overexpression of Akt1 specifically in the fat body and by mutants in widerborst (wdb), the B'-subunit of the phosphatase PP2A, known to downregulate Akt1 by dephosphorylation. Together, our data suggest that CycG acts at the level of Akt1 to regulate growth and metabolism via PP2A in Drosophila. PMID- 26274449 TI - Origin of Enthalpic Depletion Forces. AB - Solutes excluded from macromolecules or colloids are known to drive depletion attractions. The established Asakura-Oosawa model, as well as subsequent theories aimed at explaining the effects of macromolecular crowding, attribute depletion forces to diminished hard-core excluded volume upon compaction, and hence predict depletion forces dominated by entropy. However, recent experiments measuring the effect of preferentially excluded solutes on protein folding and macromolecular association find these forces can also be enthalpic. We use simulations of macromolecular association in explicit binary cosolute-solvent mixtures, with solvent and cosolute intermolecular interactions that go beyond hard-cores, to show that not all cosolutes conform to the established entropically dominated model. We further demonstrate how the enthalpically dominated depletion forces that we find can be well described within an Asakura-Oosawa like model provided that the hard-core macromolecule-cosolute potential of mean force is augmented by a "soft" step-like repulsion. PMID- 26274450 TI - Charge Trapping in Photovoltaically Active Perovskites and Related Halogenoplumbate Compounds. AB - Halogenoplumbate perovskites (MeNH3PbX3, where X is I and/or Br) have emerged as promising solar panel materials. Their limiting photovoltaic efficiency depends on charge localization and trapping processes that are presently insufficiently understood. We demonstrate that in halogenoplumbate materials the holes are trapped by organic cations (that deprotonate from their oxidized state) and Pb(2+) cations (as Pb(3+) centers), whereas the electrons are trapped by several Pb(2+) cations, forming diamagnetic lead clusters that also serve as color centers. In some cases, paramagnetic variants of these clusters can be observed. We suggest that charge separation in the halogenoplumbates resembles latent image formation in silver halide photography. Electron and hole trapping by lead clusters in extended dislocations in the bulk may be responsible for accumulation of trapped charge observed in this photovoltaic material. PMID- 26274451 TI - Structure and Properties of Platinum, Gold and Mercury Nanowires Grown in Superfluid Helium. AB - Webs consisting of nanowires made of gold, platinum and mercury were produced by the technique based on laser ablation of metals inside superfluid helium. Their morphology and structure as well as their electrical conductivity have been studied. Diameters of gold and platinum nanowires are 4.5 and 3 nm, respectively. Fortunately, they are close to diameters of nanospheres made of these metals, which, as known from the literature, possess anomalous catalytic activity. Web resistivities for all metals up to room temperature are controlled by conductive electron scattering on a wire surface, thus they are almost independent of T. Nanowires in the webs are electrically interconnected, and therefore the web can be used as a catalyst without any support. Possible advantages of this type of nanocatalyst are outlined. PMID- 26274452 TI - Protein Thermal Conductivity Measured in the Solid State Reveals Anharmonic Interactions of Vibrations in a Fractal Structure. AB - Energy processes and vibrations in biological macromolecules such as proteins ultimately dictate biological, chemical, and physical functions in living materials. These energetic vibrations in the ribbon-like motifs of proteins interact on self-similar structures and fractal-like objects over a range of length scales of the protein (a few angstroms to the size of the protein itself, a few nanometers). In fact, the fractal geometries of protein molecules create a complex network of vibrations; therefore, proteins represent an ideal material system to study the underlying mechanisms driving vibrational thermal transport in a dense, fractal network. However, experimental studies of thermal energy transport in proteins have been limited to dispersive protein suspensions, which limits the knowledge that can be extracted about how vibrational energy is transferred in a pure protein solid. We overcome this by synthesizing solid, water-insoluble protein films for thermal conductivity measurements via time domain thermoreflectance. We measure the thermal conductivity of bovine serum albumin and myoglobin solid films over a range of temperatures from 77 to 296 K. These temperature trends indicate that anharmonic coupling of vibrations in the protein is contributing to thermal conductivity. This first-ever observation of anharmonic-like trends in the thermal conductivity of a fully dense protein forms the basis of validation of seminal theories of vibrational energy-transfer processes in fractal objects. PMID- 26274453 TI - Intramolecular Processes Revealed Using UV-Laser-Induced IR-Fluorescence: A New Perspective on the "Channel Three" of Benzene. AB - Radiative relaxation in the infrared (IR) is common following nonradiative electronic relaxation processes, but it is rarely measured. We present ultraviolet laser-induced infrared fluorescence (UV-LIIRF) excitation spectroscopy and dispersed UV-LIIRF spectroscopy of gas phase benzene vibronically excited around the onset of channel 3, using a homemade spectrometer. We found that the vibrational IR fluorescence yield is clearly higher when benzene is excited above the onset than when it is excited below. Significant changes in dispersed IR emission profiles resulting from excitations below and above the onset of channel 3 were also observed. These results suggest that isomerization of benzene toward fulvene occurs efficiently below the opening of channel 3 and confirm that channel 3 involves a photophysical relaxation pathway that efficiently competes with isomerization. PMID- 26274454 TI - Atomic Interdiffusion and Diffusive Stabilization of Cobalt by Copper During Atomic Layer Deposition from Bis(N-tert-butyl-N'-ethylpropionamidinato) Cobalt(II). AB - Electromigration of copper in integrated circuits leads to device failure. Potential solutions involve capping the copper with ultrathin cobalt films. We report the properties of cobalt films after deposition on polycrystalline Cu at 265 degrees C by atomic layer deposition from H2 and bis(N-tert-butyl-N' ethylpropionamidinato) cobalt(II) (CoAMD). We find intermixing of Co and Cu producing a transition layer on the Cu nearly as thick as the Co-rich overlayer. X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry depth profiling reveal that a finite amount of Cu continuously segregates to the progressing Co surface, minimizing the free surface energy, throughout deposition up to at least 16 nm. The Cu-stabilized Co film initially follows 2D growth and strain-relieving 3D crystal formation is apparent beyond 2 nm of film growth. Depth profiling indicates that Cu likely diffuses within the Co film and along the polycrystalline Co grain boundaries. PMID- 26274455 TI - The Importance of Perovskite Pore Filling in Organometal Mixed Halide Sensitized TiO2-Based Solar Cells. AB - Emerging from the field of dye-sensitized solar cells, organometal halide perovskite-based solar cells have recently attracted considerable attention. In these devices, the perovskite light absorbers can also be used as charge transporting materials, changing the requirements for efficient device architectures. The perovskite deposition can vary from merely sensitizing the TiO2 electron transporting scaffold as an endowment of small nanoparticles, to completely filling the pores where it acts as both light absorber and hole transporting material in one. By decreasing the TiO2 scaffold layer thickness, we change the solar cell architecture from perovskite-sensitized to completely perovskite-filled. We find that the latter case leads to improvements in device performance because higher electron densities can be sustained in the TiO2, improving electron transport rates and photovoltage. Importantly, the primary recombination pathway between the TiO2 and the hole transporting material is blocked by the perovskite itself. This understanding helps to rationalize the high voltages attainable on mesoporous TiO2-based perovskite solar cells. PMID- 26274456 TI - CdSeS Nanowires: Compositionally Controlled Band Gap and Exciton Dynamics. AB - CdS, CdSe, and ternary CdSexS(1-x) are some of the most widely studied II-VI semiconductors due to their broad range of applications and promising performance in numerous systems. One-dimensional semiconductor nanowires offer the ability to conduct charges efficiently along the length of the wire, which has potential charge transport benefits compared to nanoparticles. Herein, we report a simple, inexpensive synthetic procedure for high quality CdSeS nanowires where the composition can be easily modulated from pure CdSe to pure CdS by simply adjusting the Se:S precursor ratio. This allows for tuning of the absorption and emission properties of the nanowires across the visible spectrum. The CdSeS nanowires have a wurtzite crystal structure and grow along the [001] direction. As measured by femtosecond transient absorption spectroscopy, the short component of the excited state lifetime remains relatively constant at ~10 ps with increasing Se; however, the contribution of this short lifetime component increased dramatically from 8.4% to 57.7% with increasing Se content. These CdSeS nanowires offer facile synthesis and widely adjustable optical properties, characteristics that give them broad potential applications in the fields of optoelectronics, and photovoltaics. PMID- 26274457 TI - UV Photofragmentation Dynamics of Protonated Cystine: Disulfide Bond Rupture. AB - Disulfide bonds (S-S) play a central role in stabilizing the native structure of proteins against denaturation. Experimentally, identification of these linkages in peptide and protein structure characterization remains challenging. UV photodissociation (UVPD) can be a valuable tool in identifying disulfide linkages. Here, the S-S bond acts as a UV chromophore and absorption of one UV photon corresponds to a sigma-sigma* transition. We have investigated the photodissociation dynamics of protonated cystine, which is a dimer of two cysteines linked by a disulfide bridge, at 263 nm (4.7 eV) using a multicoincidence technique in which fragments coming from the same fragmentation event are detected. Two types of bond cleavages are observed corresponding to the disulfide (S-S) and adjacent C-S bond ruptures. We show that the S-S cleavage leads to three different fragment ions via three different fragmentation mechanisms. The UVPD results are compared to collision-induced dissociation (CID) and electron-induced dissociation (EID) studies. PMID- 26274458 TI - Defect Tolerant Semiconductors for Solar Energy Conversion. AB - Defect tolerance is the tendency of a semiconductor to keep its properties despite the presence of crystallographic defects. Scientific understanding of the origin of defect tolerance is currently missing. Here we show that semiconductors with antibonding states at the top of the valence band are likely to be tolerant to defects. Theoretical calculations demonstrate that Cu3N with antibonding valence band maximum has shallow intrinsic defects and no surface states, in contrast to GaN with bonding valence band maximum. Experimental measurements indicate shallow native donors and acceptors in Cu3N thin films, leading to 10(16)-10(17) cm(-3) doping with either electrons or holes depending on the growth conditions. The experimentally measured bipolar doping and the solar matched optical absorption onset (1.4 eV) make Cu3N a promising candidate absorber for photovoltaic and photoelectrochemical solar cells, despite the calculated indirect fundamental band gap (1.0 eV). These conclusions can be extended to other materials with antibonding character of the valence band, defining a class of defect-tolerant semiconductors for solar energy conversion applications. PMID- 26274459 TI - Tuning the Stability of Surface Intermediates Using Adsorbed Oxygen: Acetate on Au(111). AB - Selective oxidative reactions promoted by gold depend critically on controlling the coverage and stability of adsorbed intermediates, as well as promoting specific bond activations of those intermediates. We demonstrate that acetate, a common intermediate in the oxidation of olefins, aldehydes, and alcohols, is destabilized by 7-10 kcal/mol by coadsorbed oxygen relative to its stability on the clean gold surface. The amount of destabilization depends on the oxygen coverage. Peak temperatures of products indicative of oxygen-assisted and clean surface bond activation differ by up to 130 K. Experiments with d3-acetate show a kinetic isotope effect of 6.9 at 400 K, indicating that the rate-limiting step of the low temperature oxygen-assisted reaction is gamma-CH bond breaking. This clearly demonstrates that coadsorbed oxygen activates gamma-CH bonds on gold and suggests that an oxygen-assisted activation may also occur for beta-CH bonds crucial in oxygen-assisted alcohol coupling on metallic gold catalysts, as predicted by theory. PMID- 26274460 TI - Quantifying Charge Extraction in Organic Solar Cells: The Case of Fluorinated PCPDTBT. AB - We introduce a new and simple method to quantify the effective extraction mobility in organic solar cells at low electric fields and charge carrier densities comparable to operation conditions under one sun illumination. By comparing steady-state carrier densities at constant illumination intensity and under open-circuit conditions, the gradient of the quasi-Fermi potential driving the current is estimated as a function of external bias and charge density. These properties are then related to the respective steady-state current to determine the effective extraction mobility. The new technique is applied to different derivatives of the well-known low-band-gap polymer PCPDTBT blended with PC70BM. We show that the slower average extraction due to lower mobility accounts for the moderate fill factor when solar cells are fabricated with mono- or difluorinated PCPDTBT. This lower extraction competes with improved generation and reduced nongeminate recombination, rendering the monofluorinated derivative the most efficient donor polymer. PMID- 26274461 TI - Air-Stable n-Doped Colloidal HgS Quantum Dots. AB - HgS nanocrystals show a strong mid-infrared absorption and a bleach of the near infrared band edge, both tunable in energy and reversibly controlled by exposure to solution ions under ambient conditions. The same effects are obtained by applying a reducing electrochemical potential, confirming that the mid-infrared absorption is the intraband transition of the quantum dot. This is the first time that stable carriers are present in the quantum state of strongly confined quantum dot in ambient conditions. The mechanism by which doping is achieved is attributed to the rigid shifts of the valence and conduction band with respect to the environment, similar to the sensitivity of the work function of surfaces to adsorbates. PMID- 26274462 TI - Ambipolar Charge Photogeneration and Transfer at GaAs/P3HT Heterointerfaces. AB - Recent work on hybrid photovoltaic systems based on conjugated polymers and III-V compound semiconductors with relatively high power conversion efficiency revived fundamental questions regarding the nature of charge separation and transfer at the interface between organic and inorganic semiconductors with different degrees of delocalization. In this work, we studied photoinduced charge generation and interfacial transfer dynamics in a prototypical photovoltaic n-type GaAs (111)B and poly(3-hexyl-thiophene) (P3HT) bilayer system. Ultrafast spectroscopy and density functional theory calculations indicate the coexistence of electron and hole transfer at the GaAs/P3HT interface, leading to the generation of long-lived species and photoinduced absorption upon creation of hybrid interfacial states. This opens up new avenues for the use of low-dimensional III-V compounds (e.g., nanowires or quantum dots) in hybrid organic/inorganic photovoltaics, where advanced bandgap and density of states engineering may also be exploited as design parameters. PMID- 26274463 TI - Molecular Dynamics Simulations of Proposed Intermediates in the CO2 + Aqueous Amine Reaction. AB - Ab initio molecular dynamics simulations of up to 210 ps have been performed on various aqueous intermediates postulated in the CO2 + amine reaction, important for CO2 capture. Observations of spontaneous deprotonation of aqueous carbamate zwitterions R1R2NHCOO(+/-) by bulk water (instead of additional amine, or via umbrella sampling) are reported apparently for the first time. Carbamic acid structures R1R2NCOOH were observed in some simulations, arising from zwitterions not via classical 1,3-H-shifts but via Grotthuss-style multiple-H(+) transfer pathways that involve bulk H2O and require carbamate anions R1R2NCOO(-) as an intermediate stage along the way. H(+)-bridging complexes, including not only Zundel ions [water.H(+).water](+) but neutral carbamate complexes [carbamate( ).H(+).water], were observed in simulation. These results should assist efforts in improving underlying mechanisms for kinetic modeling. PMID- 26274464 TI - Orbital Topology Controlling Charge Injection in Quantum-Dot-Sensitized Solar Cells. AB - Quantum-dot-sensitized solar cells are emerging as a promising development of dye sensitized solar cells, where photostable semiconductor quantum dots replace molecular dyes. Upon photoexcitation of a quantum dot, an electron is transferred to a high-band-gap metal oxide. Swift electron transfer is crucial to ensure a high overall efficiency of the solar cell. Using femtosecond time-resolved spectroscopy, we find the rate of electron transfer to be surprisingly sensitive to the chemical structure of the linker molecules that attach the quantum dots to the metal oxide. A rectangular barrier model is unable to capture the observed variation. Applying bridge-mediated electron-transfer theory, we find that the electron-transfer rates depend on the topology of the frontier orbital of the molecular linker. This promises the capability of fine tuning the electron transfer rates by rational design of the linker molecules. PMID- 26274465 TI - Size-Dependent Plasmonic Resonances from Large-Scale Quantum Simulations. AB - For metallic nanoparticles less than 10 nm in diameter, localized surface plasmon resonances (LSPRs) become sensitive to the quantum nature of conduction electrons. In this regime, experimental probes of size-dependent LSPRs are particularly challenging, and contradictory results are often reported. Unfortunately, quantum mechanical simulations based on time-dependent Kohn-Sham density functional theory (TD-KSDFT) are computationally too expensive to tackle metal particles larger than 2 nm. Herein, we present a time-dependent orbital free density functional theory (TD-OFDFT) that accurately captures the dynamic response of electrons in the presence of realistic ionic potentials. The TD-OFDFT method offers a comparable accuracy as TD-KSDFT but with a much lower computational cost. Using TD-OFDFT, we study size-dependent LSPRs on Na nanoparticles with diameters from 0.7 to 12.3 nm. The optical absorption spectra exhibit a nonmonotonic behavior from blue shift to red shift and back to blue shift as the particle size decreases. Three principal plasmon modes are identified, and their physical origins are elucidated. Competing physical mechanisms responsible for the nonmonotonic size dependence are discussed. The TD OFDFT provides a unified theoretical framework that bridges the gap between classical electromagnetic theory and quantum mechanical theory for plasmonics and nanophotonics. PMID- 26274466 TI - A Direct Link between the Fragile-to-Strong Transition and Relaxation in Supercooled Liquids. AB - It is known that both the fragile-to-strong (F-S) transition and relaxation processes occur in numerous supercooled liquids upon cooling toward the glass transition temperature. The key question is whether and how these two dynamic processes are correlated. Here, we show a direct link between the two processes for both metallic glass-forming liquids (MGFLs) with different fragilities and also for nonmetallic glass-forming liquids. By comparing the F-S transition extent parameter f with the parameter r that characterizes the competition between the alpha and the slow beta relaxations, we have discovered a negative exponential connection between the two parameters of supercooled liquids. The finding indicates that the slow beta relaxation plays a dominant role in the F-S transition. This work provides new insight into the microscopic mechanism of the F-S transition and creates a strong basis for predicting whether and to what extent the F-S transition occurs in supercooled liquids. PMID- 26274467 TI - Direct Evidence of Confined Water in Room-Temperature Ionic Liquids by Complementary Use of Small-Angle X-ray and Neutron Scattering. AB - The direct evidence of confined water ("water pocket") inside hydrophilic room temperature ionic liquids (RTILs) was obtained by complementary use of small angle X-ray scattering and small-angle neutron scattering (SAXS and SANS). A large contrast in X-ray and neutron scattering cross-section of deuterons was used to distinguish the water pocket from the RTIL. In addition to nanoheterogeneity of pure RTILs, the water pocket formed in the water-rich region. Both water concentration and temperature dependence of the peaks in SANS profiles confirmed the existence of the hidden water pocket. The size of the water pocket was estimated to be ~3 nm, and D2O aggregations were well-simulated on the basis of the observed SANS data. PMID- 26274468 TI - On the Coupling between the Collective Dynamics of Proteins and Their Hydration Water. AB - Picosecond time scale dynamics of hydrated proteins has been connected with the onset of biological activity as it coincides with solvent-solute hydrogen bond rearrangements and amino acid rotational relaxation time scales. The presence and fluctuations of protein hydration water (PHW) largely influence protein motions that are believed to be slaved to those of the solvent, yet to date, how protein and hydration water dynamics are coupled remains unclear. Here, we provide a significant advance in characterizing this coupling; we present the first full study of both the longitudinal and transverse coherent collective motions in a protein-solvent system. The data show unexpectedly the presence in the water dynamics of collective modes belonging to the protein. The properties of these modes, in particular, their propagation velocities and amplitudes, indicate a strengthening of the interactions and a higher rigidity of the network of solvent molecules close to the protein surface. Accordingly, the present study presents the most compelling and clear evidence of a very strong dynamical coupling between a protein and its hydration water, previously suggested by studies using various experimental techniques. PMID- 26274469 TI - Modulating the Arrangement of Charged Nanotubes by Ionic Strength in Salty Water. AB - Despite the important role and potential application of charged cylindrical polyelectrolytes, biomacromolecules, and self-assembles, salt-modulated organization of those 1D charged nanostructures remains a topic relatively unexplored with an obscure underlying mechanism. In this Letter, the aggregation of oriented nanotubes self-assembled by ionic aromatic oligoamide in aqueous solution of NaCl over a wide concentration range is probed via small-angle X-ray scattering and a transmission electron microscope. The arrangement of nanotubes undergoes order-disorder transition sequences from an ordered rectangular phase to hexagonal packing and then to a lamellar gel. The observed transitions are understood by ionic effects on the electrostatic interaction between charged nanotubes and osmotic pressure due to ion partitioning. Above the physiological condition, electrostatic interactions are largely screened by the salts, while osmotic effects start to regulate the aggregation behavior and concomitantly deform the nanotubes. The study demonstrates rich phase behaviors of ordered, charged 1D nanostructures by tuning the ionic strength and underlying key physical principles. PMID- 26274470 TI - Mechanism of Transition-Metal Nanoparticle Catalytic Graphene Cutting. AB - Catalytic cutting by transition-metal (TM) particles is a promising method for the synthesizing of high-quality graphene quantum dots and nanoribbons with smooth edges. Experimentally, it is observed that the cutting always results in channels with zigzag (ZZ) or armchair (AC) edges. However, the driving force that is responsible for such a cutting behavior remains a puzzle. Here, by calculating the interfacial formation energies of the TM-graphene edges with ab initio method, we show that the surface of a catalyst particle tends to be aligned along either AC or ZZ direction of the graphene lattice, and thus the cutting of graphene is guided as such. The different cutting behaviors of various catalysts are well-explained based on the competition between TM-passivated graphene edges and the etching-agent-terminated ones. Furthermore, the kinetics of graphene catalytic cutting along ZZ and AC directions, respectively, are explored at the atomic level. PMID- 26274471 TI - Absolute Photoluminescence Quantum Yield Measurement in a Complex Nanoscopic System with Multiple Overlapping States. AB - Using a metal nanocavity, we measure absolute values of the photoluminescence quantum yield in a mixture of different types of chromophores (dye molecules and semiconductor nanocrystals). We show that measurements can be performed in an attoliter volume, both in liquid and solid phases, even if both types of chromophores absorb and emit light in the same spectral range. The method is based on recording photoluminescence decay curves of the chromophore mixture as a function of the cavity length. Changing the distance between the cavity mirrors modifies the local density of states of the electromagnetic field and thus, the radiative transition rate of the enclosed emitters. By extracting individual decay components, corresponding to the different types of the emitters, we determine their quantum yield values separately and simultaneously. The nanocavity-based method opens up new perspectives for studying quantum emitters in complex photophysical systems, for instance, multichromophoric thin films, fluorescent proteins, or dyes incorporated into a lipid bilayer. PMID- 26274472 TI - Distant- and Shape-Dependent Excitation Energy Transfer in Nanohybrid Systems: Computations on a Pheophorbide-alpha CdSe Nanocrystal Complex. AB - The combination of semiconductor nanocrystals (NCs) and molecules for efficient electronic excitation energy transfer is expected to be a promising ingredient of novel hybrid photovoltaic devices. Here energy transfer from a CdSe NC to the tetrapyrrole-type Pheophorbide-a molecule (Pheo) is studied theoretically. The rate expression accounts for the correct NC-Pheo transfer coupling, for the multitude of NC single exciton levels as well as their thermal distribution, and for the electron-vibrational Pheo states. A spherical Cd1159Se1450 NC is compared with a similar large NC of pyramidal and hemisphere shape. Because of the different exciton energies and wave functions, the transfer rates differ somewhat. For all three types of NC, however, the Coulomb correlation essentially determines the magnitude of the transfer coupling and the exciton energy. In any case, the energy-transfer coupling is below 1 meV, excluding hybrid-state formation. PMID- 26274473 TI - Nylon-Oligomer Hydrolase Promoting Cleavage Reactions in Unnatural Amide Compounds. AB - The active site of 6-aminohexanoate-dimer hydrolase, a nylon-6 byproduct degrading enzyme with a beta-lactamase fold, possesses a Ser112/Lys115/Tyr215 catalytic triad similar to the one of penicillin-recognizing family of serine reactive hydrolases but includes a unique Tyr170 residue. By using a reactive quantum mechanics/molecular mechanics (QM/MM) approach, we work out its catalytic mechanism and related functional/structural specificities. At variance with other peptidases, we show that the involvement of Tyr170 in the enzyme-substrate interactions is responsible for a structural variation in the substrate-binding state. The acylation via a tetrahedral intermediate is the rate-limiting step, with a free-energy barrier of ~21 kcal/mol, driven by the catalytic triad Ser112, Lys115, and Tyr215, acting as a nucleophile, general base, and general acid, respectively. The functional interaction of Tyr170 with this triad leads to an efficient disruption of the tetrahedral intermediate, promoting a conformational change of the substrate favorable for proton donation from the general acid. PMID- 26274474 TI - Achieving Rigorous Accelerated Conformational Sampling in Explicit Solvent. AB - Molecular dynamics simulations can provide valuable atomistic insights into biomolecular function. However, the accuracy of molecular simulations on general purpose computers depends on the time scale of the events of interest. Advanced simulation methods, such as accelerated molecular dynamics, have shown tremendous promise in sampling the conformational dynamics of biomolecules, where standard molecular dynamics simulations are nonergodic. Here we present a sampling method based on accelerated molecular dynamics in which rotatable dihedral angles and nonbonded interactions are boosted separately. This method (RaMD-db) is a different implementation of the dual-boost accelerated molecular dynamics, introduced earlier. The advantage is that this method speeds up sampling of the conformational space of biomolecules in explicit solvent, as the degrees of freedom most relevant for conformational transitions are accelerated. We tested RaMD-db on one of the most difficult sampling problems - protein folding. Starting from fully extended polypeptide chains, two fast folding alpha-helical proteins (Trpcage and the double mutant of C-terminal fragment of Villin headpiece) and a designed beta-hairpin (Chignolin) were completely folded to their native structures in very short simulation time. Multiple folding/unfolding transitions could be observed in a single trajectory. Our results show that RaMD db is a promisingly fast and efficient sampling method for conformational transitions in explicit solvent. RaMD-db thus opens new avenues for understanding biomolecular self-assembly and functional dynamics occurring on long time and length scales. PMID- 26274475 TI - First-Principles Studies of Li Nucleation on Graphene. AB - We study the Li clustering process on graphene and obtain the geometry, nucleation barrier, and electronic structure of the clusters using first principles calculations. We estimate the concentration-dependent nucleation barrier for Li on graphene. While the nucleation occurs more readily with increasing Li concentration, possibly leading to the dendrite formation and failure of the Li-ion battery, the existence of the barrier delays nucleation and may allow Li storage on graphene. Our electronic structure and charge transfer analyses reveal how the fully ionized Li adatoms transform to metallic Li during the cluster growth on graphene. PMID- 26274476 TI - Chemical and Electrochemical Differences in Nonaqueous Li-O2 and Na-O2 Batteries. AB - We present a comparative study of nonaqueous Li-O2 and Na-O2 batteries employing an ether-based electrolyte. The most intriguing difference between the two batteries is their respective galvanostatic charging overpotentials: a Na-O2 battery exhibits a low overpotential throughout most of its charge, whereas a Li O2 battery has a low initial overpotential that continuously increases to very high voltages by the end of charge. However, we find that the inherent kinetic Li and Na-O2 overpotentials, as measured on a flat glassy carbon electrode in a bulk electrolysis cell, are similar. Measurement of each batteries' desired product yield, YNaO2 and YLi2O2, during discharge and rechargeability by differential electrochemical mass spectrometry (DEMS) indicates that less chemical and electrochemical decomposition occurs in a Na-O2 battery during the first Galvanostatic discharge-charge cycle. We therefore postulate that reactivity differences (Li2O2 being more reactive than NaO2) between the major discharge products lead to the observed charge overpotential difference between each battery. PMID- 26274478 TI - Cite with a Sight. PMID- 26274477 TI - Development of Ultraviolet-Ultraviolet Hole-Burning Spectroscopy for Cold Gas Phase Ions. AB - A new ultraviolet-ultraviolet hole-burning (UV-UV HB) spectroscopic scheme has been developed for cold gas-phase ions in a quadrupole ion trap (QIT) connected with a time-of-flight (TOF) mass spectrometer. In this method, a pump UV laser generates a population hole for the ions trapped in the cold QIT, and a second UV laser (probe) monitors the population hole for the ions extracted to the field free region of the TOF mass spectrometer. Here, the neutral fragments generated by the UV dissociation of the ions with the second laser are detected. This UV-UV HB spectroscopy was applied to protonated dibenzylamine and to protonated uracil. Protonated uracil exhibits two strong electronic transitions; one has a band origin at 31760 cm(-1) and the other at 39000 cm(-1). From the UV-UV HB measurement and quantum chemical calculations, the lower-energy transition is assigned to the enol-keto tautomer and the higher-energy one to the enol-enol tautomer. PMID- 26274479 TI - Diagnostic Imaging in Flames with Instantaneous Planar Coherent Raman Spectroscopy. AB - Spatial mapping of temperature and molecular species concentrations is vitally important in studies of gaseous chemically reacting flows. Temperature marks the evolution of heat release and energy transfer, while species concentration gradients provide critical information on mixing and chemical reaction. Coherent anti-Stokes Raman spectroscopy (CARS) was pioneered in measurements of such processes almost 40 years ago and is authoritative in terms of the accuracy and precision it may provide. While a reacting flow is fully characterized in three dimensional space, a limitation of CARS has been its applicability as a point wise measurement technique, motivating advancement toward CARS imaging, and attempts have been made considering one-dimensional probing. Here, we report development of two-dimensional CARS, with the first diagnostics of a planar field in a combusting flow within a single laser pulse, resulting in measured isotherms ranging from 450 K up to typical hydrocarbon flame temperatures of about 2000 K with chemical mapping of O2 and N2. PMID- 26274480 TI - Toward Higher Energy Conversion Efficiency for Solid Polymer Electrolyte Dye Sensitized Solar Cells: Ionic Conductivity and TiO2 Pore-Filling. AB - Even though the solid polymer electrolyte has many intrinsic advantages over the liquid electrolyte, its ionic conductivity and mesopore-filling are much poorer than those of the liquid electrolyte, limiting its practical application to electrochemical devices such as dye-sensitized solar cells (DSCs). Two major shortcomings associated with utilizing solid polymer electrolytes in DSCs are first discussed, low ionic conductivity and poor pore-filling in mesoporous photoanodes for DSCs. In addition, future directions for the successful utilization of solid polymer electrolytes toward improving the performance of DSCs are proposed. For instance, the facilitated mass-transport concept could be applied to increase the ionic conductivity. Modified biphasic and triple-phasic structures for the photoanode are suggested to take advantage of both the liquid- and solid-state properties of electrolytes. PMID- 26274481 TI - Theoretical Study of Plasmon-Enhanced Surface Catalytic Coupling Reactions of Aromatic Amines and Nitro Compounds. AB - Taking advantage of the unique capacity of surface plasmon resonance, plasmon enhanced heterogeneous catalysis has recently come into focus as a promising technique for high performance light-energy conversion. This work performs a theoretical study on the reaction mechanism for conversions of p-aminothiophenol (PATP) and p-nitrothiophenol (PNTP) to aromatic azo species, p,p' dimercaptoazobenzene (DMAB). In the absence of O2 or H2, the plasmon-driven photocatalysis mechanism (hot electron-hole reactions) is the major reaction channel. In the presence of O2 or H2, the plasmon-assisted surface catalysis mechanism (activated oxygen/hydrogen reactions) is the major reaction channel. The present results show that the coupling reactions of PATP and PNTP strongly depend on the solution pH, the irradiation wavelength, the irradiation power, and the nature of metal substrates as well as the surrounding atmosphere. The present study has drawn a fundamental physical picture for understanding plasmon-enhanced heterogeneous catalysis. PMID- 26274482 TI - Resolving Discrepancies in the Measurements of the Interfacial Tension for the CO2 + H2O Mixture by Computer Simulation. AB - Literature values regarding the pressure dependence of the interfacial tension of the system of carbon dioxide (CO2) + water (H2O) show an unexplained divergence and scatter at the transition between low-pressure gas-liquid equilibrium and the high-pressure liquid-liquid equilibrium. We employ the Statistical Associating Fluid Theory (SAFT) and canonical molecular dynamics simulations based on the corresponding coarse grained force field to map out the phase diagram of the mixture and the interfacial tension for this system. We showcase how at ambient temperatures a triple point (gas-liquid-liquid) is expected and detail the implications that the appearance of the third phase has on the interfacial tensions of the system. PMID- 26274483 TI - Quantum-Mechanical Prediction of Nanoscale Photovoltaics. AB - Previous simulations of photovoltaic devices are based on classical models, which neglect the atomistic details and quantum-mechanical effects besides the dependence on many empirical parameters. Here, within the nonequilibrium Green's function formalism, we present a quantum-mechanical study of the performance of inorganic nanowire-based photovoltaic devices. On the basis of density-functional tight-binding theory, the method allows simulation of current-voltage characteristics and optical properties of photovoltaic devices without relying on empirical parameters. Numerical studies of silicon nanowire-based devices of realistic sizes with 10 000 atoms are performed, and the results indicate that atomistic details and nonequilibrium conditions have a clear impact on the photoresponse of the devices. PMID- 26274484 TI - Crystal Structures, Optical Properties, and Effective Mass Tensors of CH3NH3PbX3 (X = I and Br) Phases Predicted from HSE06. AB - The crystal structures are successfully established for tetragonal and orthorhombic CH3NH3PbX3 (X = I and Br). The equilibrium lattice parameters are computed by the DFT+D2 method, and the results are compared to experimental values. The band dispersions and electronic densities of states are calculated by HSE06, showing that their band gaps are in the range from 1.63 to 2.3 eV. Although the calculated dielectric functions of MAPbX3 compounds are similar to other semiconductors, the absorption spectra of their bulk crystals are drifted away from visible light spectrum. The effective mass tensors of holes and electrons are also evaluated in three principal directions at the Gamma point. The anisotropies in the effective masses of the hole and electron are illustrated for two orthorhombic phases. PMID- 26274485 TI - Atom-Level Understanding of the Sodiation Process in Silicon Anode Material. AB - Despite the exceptionally large capacities in Li ion batteries, Si has been considered inappropriate for applications in Na ion batteries. We report an atomic-level study on the applicability of a Si anode in Na ion batteries using ab initio molecular dynamics simulations. While crystalline Si is not suitable for alloying with Na atoms, amorphous Si can accommodate 0.76 Na atoms per Si atom, corresponding to a specific capacity of 725 mA h g(-1). Bader charge analyses reveal that the sodiation of an amorphous Si electrode continues until before the local Na-rich clusters containing neutral Na atoms are formed. The amorphous Na0.76Si phase undergoes a volume expansion of 114% and shows a Na diffusivity of 7 * 10(-10) cm(2) s(-1) at room temperature. Overall, the amorphous Si phase turns out quite attractive in performance compared to other alloy-type anode materials. This work suggests that amorphous Si might be a competitive candidate for Na ion battery anodes. PMID- 26274486 TI - Bilayer Phosphorene: Effect of Stacking Order on Bandgap and Its Potential Applications in Thin-Film Solar Cells. AB - Phosphorene, a monolayer of black phosphorus, is promising for nanoelectronic applications not only because it is a natural p-type semiconductor but also because it possesses a layer-number-dependent direct bandgap (in the range of 0.3 to 1.5 eV). On basis of the density functional theory calculations, we investigate electronic properties of the bilayer phosphorene with different stacking orders. We find that the direct bandgap of the bilayers can vary from 0.78 to 1.04 eV with three different stacking orders. In addition, a vertical electric field can further reduce the bandgap to 0.56 eV (at the field strength 0.5 V/A). More importantly, we find that when a monolayer of MoS2 is superimposed with the p-type AA- or AB-stacked bilayer phosphorene, the combined trilayer can be an effective solar-cell material with type-II heterojunction alignment. The power conversion efficiency is predicted to be ~18 or 16% with AA- or AB-stacked bilayer phosphorene, higher than reported efficiencies of the state-of-the-art trilayer graphene/transition metal dichalcogenide solar cells. PMID- 26274487 TI - Factors associated with the development of dental caries in children and adolescents in studies employing the life course approach: a systematic review. AB - The purpose of this article was to conduct a systematic review of studies that used the life course approach to evaluate the association between factors experienced in early life and throughout the lifetime and the development of dental caries in children and adolescents. A systematic search of five electronic databases was carried out. Hand searches of the reference lists of the included articles and a gray literature search were also performed. Quantitative studies that adopted the life course approach to examine the factors associated with the development of dental caries in children and adolescents were selected. Abstracts were screened by two reviewers. Reports with relevant abstracts received full text review and were examined for inclusion in the present systematic review. Qualitative evaluation of the included articles was carried out using the Newcastle-Ottawa Scale. As a result of the high degree of heterogeneity, meta analysis was not feasible. Among the 48 articles submitted to full-text analysis, 11 were included in the present systematic review. Different life course factors were associated with the development of dental caries among children and adolescents, including sociodemographic, biological, psychological, and oral health behaviors, as well as the dental status of mothers, children, and adolescents. PMID- 26274488 TI - Effect of 6-8 weeks of oral ursodeoxycholic acid administration on serum concentrations of fasting and postprandial bile acids and biochemical analytes in healthy dogs. AB - BACKGROUND: Ursodeoxycholic acid (UDCA) is commonly used for the treatment of hepatobiliary disease. UDCA is a bile acid that can be detected in the bile acid assay. Its effect on biochemical analytes is unknown. OBJECTIVES: The aim of this study was to determine the effect of 6-8 weeks of UDCA administration on fasting and postprandial concentrations of serum bile acids (SBA), cholesterol, triglycerides, bilirubin, and liver enzyme activities in healthy dogs. METHODS: Twenty healthy dogs received UDCA for 6-8 weeks. CBC, biochemistry profile, urinalysis, fasting and postprandial SBA, and hepatobiliary ultrasound examination were performed prior to starting UDCA (timepoint 0) and after 6-8 weeks of therapy, while animals were still receiving UDCA (timepoint 1). Timepoint 0 and timepoint 1 values were compared with a paired t-test. SBA were remeasured 72 hours after UDCA discontinuation. RESULTS: Only mean fasting SBA at timepoint 1 increased significantly (P = .03) from timepoint 0 (2.26 MUmol/L at time 0 and 3.81 MUmol/L at time 1) but were not elevated above the normal reference interval (0-9 MUmol/L). Two dogs had timepoint 1 fasting SBA above the reference interval (10 and 11.7 MUmol/L). One dog had timepoint 1 postprandial SBA above the reference interval at 20.1 MUmol/L (reference interval 0-17 MUmol/L). Repeat SBA 72 hours after UDCA discontinuation were normal. CONCLUSIONS: Long-term administration of UDCA to healthy dogs may increase fasting SBA above pretreatment values (typically within the reference interval). Long-term administration of UDCA to healthy dogs does not alter liver enzyme activities, and bilirubin, cholesterol, or triglyceride concentrations. PMID- 26274490 TI - The management of cytotoxic chemotherapy extravasation: a systematic review of the literature to evaluate the evidence underpinning contemporary practice. AB - Management of cytotoxic drug extravasation remains contentious, with differing views on the most effective management strategy. With the increasing drive to provide effective, evidence-based healthcare, while ensuring the patient experience of the treatment provided plays a significant part in the development of clinical practice guidelines, the purpose of this literature review was to both critically analyse the quality of evidence that underpins contemporary practice and to determine if the patient experience is taken into account. A literature search was undertaken sourcing publications from the 1960s to July 2014 identifying all studies detailing strategies aimed at preventing the need for surgical debridement and all studies evaluating extravasation management from the patient's perspective. No conclusive evidence was found to suggest one clinical strategy as more effective than the other. No studies were identified that evaluated outcome from the patient's perspective. It is therefore suggested that outcomes-based research should underpin contemporary extravasation management guidelines to determine what the final outcome or 'end result' is and how this impacts on the patient and that the current lack of research into the patient experience of extravasation management is an area that needs to be addressed. PMID- 26274489 TI - Molecular Detection of 10 of the Most Unwanted Alien Forest Pathogens in Canada Using Real-Time PCR. AB - Invasive alien tree pathogens can cause significant economic losses as well as large-scale damage to natural ecosystems. Early detection to prevent their establishment and spread is an important approach used by several national plant protection organizations (NPPOs). Molecular detection tools targeting 10 of the most unwanted alien forest pathogens in Canada were developed as part of the TAIGA project (http://taigaforesthealth.com/). Forest pathogens were selected following an independent prioritization. Specific TaqMan real-time PCR detection assays were designed to function under homogeneous conditions so that they may be used in 96- or 384-well plate format arrays for high-throughput testing of large numbers of samples against multiple targets. Assays were validated for 1) specificity, 2) sensitivity, 3) precision, and 4) robustness on environmental samples. All assays were highly specific when evaluated against a panel of pure cultures of target and phylogenetically closely-related species. Sensitivity, evaluated by assessing the limit of detection (with a threshold of 95% of positive samples), was found to be between one and ten target gene region copies. Precision or repeatability of each assay revealed a mean coefficient of variation of 3.4%. All assays successfully allowed detection of target pathogen on positive environmental samples, without any non-specific amplification. These molecular detection tools will allow for rapid and reliable detection of 10 of the most unwanted alien forest pathogens in Canada. PMID- 26274491 TI - Copper Contamination Impairs Herbivore Initiation of Seaweed Inducible Defenses and Decreases Their Effectiveness. AB - Seaweed-herbivore interactions are often mediated by environmental conditions, yet the roles of emerging anthropogenic stressors on these interactions are poorly understood. For example, chemical contaminants have unknown consequences on seaweed inducible resistance and herbivore response to these defenses despite known deleterious effects of contaminants on animal inducible defenses. Here, we investigated the effect of copper contamination on the interactions between a snail herbivore and a brown seaweed that displays inducible resistance to grazing. We examined seaweed inducible resistance and its effectiveness for organisms exposed to copper at two time points, either during induction or after herbivores had already induced seaweed defenses. Under ambient conditions, non grazed tissues were more palatable than grazed tissues. However, copper additions negated the preference for non-grazed tissues regardless of the timing of copper exposure, suggesting that copper decreased both how herbivores initiated these inducible defenses and their subsequent effectiveness. Copper decreased stimulation of defenses, at least in part, by suppressing snail grazing pressure the cue that turns inducible defenses on. Copper decreased effectiveness of defenses by preventing snails from preferentially consuming non-grazed seaweed. Thus, contaminants can potentially stress communities by changing seaweed herbivore interactions mediated via inducible defenses. Given the ubiquity of seaweed inducible resistance and their potential influence on herbivores, we hypothesize that copper contamination may change the impact of these resistant traits on herbivores. PMID- 26274494 TI - Insomnia symptoms and behavioural health symptoms in veterans 1 year after traumatic brain injury. AB - OBJECTIVE: Insomnia and behavioural health symptoms 1 year after traumatic brain injury (TBI) were examined in a clinical sample representative of veterans who received inpatient treatment for TBI-related issues within the Veterans Health Administration. METHODS: This was a cross-sectional sub-study (n = 112) of the Polytrauma Rehabilitation Centres' traumatic brain injury model system programme. Prevalence estimates of insomnia, depression, general anxiety, nightmares, headache and substance use, stratified by injury severity, were derived. Univariate logistic regression was used to examine unadjusted effects for each behavioural health problem and insomnia by injury severity. RESULTS: Participants were primarily male, < 30 years old and high school educated. Twenty-nine per cent met study criteria for insomnia; those with mild TBI were significantly more likely to meet criteria (43%) than those with moderate/severe TBI (22%), chi2(1, n = 112) = 5.088, p <= 0.05. Univariable logistic regression analyses revealed depressive symptoms and general anxiety were significantly associated with insomnia symptoms after TBI of any severity. Headache and binge drinking were significantly inversely related to insomnia symptoms after moderate/severe TBI, but not MTBI. CONCLUSIONS: Veterans with history of TBI, of any severity, and current insomnia symptoms may be at increased risk for depression and anxiety 1 year after TBI. PMID- 26274495 TI - Risk of cutaneous toxicities in patients with solid tumors treated with immune checkpoint inhibitors: a meta-analysis. AB - BACKGROUND: We performed a meta-analysis of the risk of cutaneous toxicities associated with immune checkpoint inhibitors. METHODS: Eligible studies included randomized trials of patients with solid tumors on immune checkpoint inhibitors (ipilimumab, nivolumab, tremelimumab, pidlizumab and pembrolizumab); describing events of rash, vitiligo and pruritus. RESULTS: A total of nine clinical trials were considered eligible for the meta-analysis. The relative risk of all-grade rash, vitiligo and pruritus was 4.06 (95% CI: 3.35-4.91; p < 0.0001), 16.3 (95% CI: 3.21-82.8; p = 0.0008) and 3.4 (95% CI: 2.24-5.16; p < 0.00001), respectively. CONCLUSION: Our meta-analysis demonstrates that immune checkpoint inhibitors are associated with an increased risk of all grade skin rash, vitiligo and pruritus. Clinicians should perform regular clinical cutaneous monitoring. PMID- 26274493 TI - Embracing failure: What the Phase III progesterone studies can teach about TBI clinical trials. AB - BACKGROUND: Despite positive preclinical studies and two positive Phase II clinical trials, two large Phase III clinical trials of progesterone treatment of acute traumatic brain injury (TBI) recently ended with negative results, so a 100% failure rate continues to plague the field of TBI trials. METHODS: This paper reviews and analyses the trial structures and outcomes and discusses the implications of these failures for future drug and clinical trial development. Persistently negative trial outcomes have led to disinvestment in new drug research by companies and policy-makers and disappointment for patients and their families, failures which represent a major public health concern. The problem is not limited to TBI. Failure rates are high for trials in stroke, sepsis, cardiology, cancer and orthopaedics, among others. RESULTS: This paper discusses some of the reasons why the Phase III trials have failed. These reasons may include faulty extrapolation from pre-clinical data in designing clinical trials and the use of subjective outcome measures that accurately reflect neither the nature of the deficits nor long-term quantitative recovery. CONCLUSIONS: Better definitions of injury and healing and better outcome measures are essential to change the embrace of failure that has dominated the field for over 30 years. This review offers suggestions to improve the situation. PMID- 26274496 TI - Response of Archaeal and Bacterial Soil Communities to Changes Associated with Outdoor Cattle Overwintering. AB - Archaea and bacteria are important drivers for nutrient transformations in soils and catalyse the production and consumption of important greenhouse gases. In this study, we investigate changes in archaeal and bacterial communities of four Czech grassland soils affected by outdoor cattle husbandry. Two show short-term (3 years; STI) and long-term impact (17 years; LTI), one is regenerating from cattle impact (REG) and a control is unaffected by cattle (CON). Cattle manure (CMN), the source of allochthonous microbes, was collected from the same area. We used pyrosequencing of 16S rRNA genes to assess the composition of archaeal and bacterial communities in each soil type and CMN. Both short- and long- term cattle impact negatively altered archaeal and bacterial diversity, leading to increase of homogenization of microbial communities in overwintering soils over time. Moreover, strong shifts in the prokaryotic communities were observed in response to cattle overwintering, with the greatest impact on archaea. Oligotrophic and acidophilic microorganisms (e.g. Thaumarchaeota, Acidobacteria, and alpha-Proteobacteria) dominated in CON and expressed strong negative response to increased pH, total C and N. Whereas copiotrophic and alkalophilic microbes (e.g. methanogenic Euryarchaeota, Firmicutes, Chloroflexi, Actinobacteria, and Bacteroidetes) were common in LTI showing opposite trends. Crenarchaeota were also found in LTI, though their trophic interactions remain cryptic. Firmicutes, Bacteroidetes, Methanobacteriaceae, and Methanomicrobiaceae indicated the introduction and establishment of faecal microbes into the impacted soils, while Chloroflexi and Methanosarcinaceae suggested increased abundance of soil-borne microbes under altered environmental conditions. The observed changes in prokaryotic community composition may have driven corresponding changes in soil functioning. PMID- 26274498 TI - Correction: Bayesian Integration of Information in Hippocampal Place Cells. PMID- 26274497 TI - Factors Associated with Mortality and Graft Failure in Liver Transplants: A Hierarchical Approach. AB - BACKGROUND: Liver transplantation has received increased attention in the medical field since the 1980s following the introduction of new immunosuppressants and improved surgical techniques. Currently, transplantation is the treatment of choice for patients with end-stage liver disease, and it has been expanded for other indications. Liver transplantation outcomes depend on donor factors, operating conditions, and the disease stage of the recipient. A retrospective cohort was studied to identify mortality and graft failure rates and their associated factors. All adult liver transplants performed in the state of Sao Paulo, Brazil, between 2006 and 2012 were studied. METHODS AND FINDINGS: A hierarchical Poisson multiple regression model was used to analyze factors related to mortality and graft failure in liver transplants. A total of 2,666 patients, 18 years or older, (1,482 males; 1,184 females) were investigated. Outcome variables included mortality and graft failure rates, which were grouped into a single binary variable called negative outcome rate. Additionally, donor clinical, laboratory, intensive care, and organ characteristics and recipient clinical data were analyzed. The mortality rate was 16.2 per 100 person-years (py) (95% CI: 15.1-17.3), and the graft failure rate was 1.8 per 100 py (95% CI: 1.5-2.2). Thus, the negative outcome rate was 18.0 per 100 py (95% CI: 16.9 19.2). The best risk model demonstrated that recipient creatinine >= 2.11 mg/dl [RR = 1.80 (95% CI: 1.56-2.08)], total bilirubin >= 2.11 mg/dl [RR = 1.48 (95% CI: 1.27-1.72)], Na+ >= 141.01 mg/dl [RR = 1.70 (95% CI: 1.47-1.97)], RNI >= 2.71 [RR = 1.64 (95% CI: 1.41-1.90)], body surface >= 1.98 [RR = 0.81 (95% CI: 0.68 0.97)] and donor age >= 54 years [RR = 1.28 (95% CI: 1.11-1.48)], male gender [RR = 1.19(95% CI: 1.03-1.37)], dobutamine use [RR = 0.54 (95% CI: 0.36-0.82)] and intubation >= 6 days [RR = 1.16 (95% CI: 1.10-1.34)] affected the negative outcome rate. CONCLUSIONS: The current study confirms that both donor and recipient characteristics must be considered in post-transplant outcomes and prognostic scores. Our data demonstrated that recipient characteristics have a greater impact on post-transplant outcomes than donor characteristics. This new concept makes liver transplant teams to rethink about the limits in a MELD allocation system, with many teams competing with each other. The results suggest that although we have some concerns about the donors features, the recipient factors were heaviest predictors for bad outcomes. PMID- 26274499 TI - Genotyping of Single Nucleotide Polymorphisms in DNA Isolated from Serum Using Sequenom MassARRAY Technology. AB - BACKGROUND: Large epidemiologic studies have the potential to make valuable contributions to the assessment of gene-environment interactions because they prospectively collected detailed exposure data. Some of these studies, however, have only serum or plasma samples as a low quantity source of DNA. METHODS: We examined whether DNA isolated from serum can be used to reliably and accurately genotype single nucleotide polymorphisms (SNPs) using Sequenom multiplex SNP genotyping technology. We genotyped 81 SNPs using samples from 158 participants in the NYU Women's Health Study. Each participant had DNA from serum and at least one paired DNA sample isolated from a high quality source of DNA, i.e. clots and/or cell precipitates, for comparison. RESULTS: We observed that 60 of the 81 SNPs (74%) had high call frequencies (>=95%) using DNA from serum, only slightly lower than the 85% of SNPs with high call frequencies in DNA from clots or cell precipitates. Of the 57 SNPs with high call frequencies for serum, clot, and cell precipitate DNA, 54 (95%) had highly concordant (>98%) genotype calls across all three sample types. High purity was not a critical factor to successful genotyping. CONCLUSIONS: Our results suggest that this multiplex SNP genotyping method can be used reliably on DNA from serum in large-scale epidemiologic studies. PMID- 26274500 TI - Real-Time PCR Quantification of Heteroplasmy in a Mouse Model with Mitochondrial DNA of C57BL/6 and NZB/BINJ Strains. AB - Mouse models are widely employed to study mitochondrial inheritance, which have implications to several human diseases caused by mutations in the mitochondrial genome (mtDNA). These mouse models take advantage of polymorphisms between the mtDNA of the NZB/BINJ and the mtDNA of common inbred laboratory (i.e., C57BL/6) strains to generate mice with two mtDNA haplotypes (heteroplasmy). Based on PCR followed by restriction fragment length polymorphism (PCR-RFLP), these studies determine the level of heteroplasmy across generations and in different cell types aiming to understand the mechanisms underlying mitochondrial inheritance. However, PCR-RFLP is a time-consuming method of low sensitivity and accuracy that dependents on the use of restriction enzyme digestions. A more robust method to measure heteroplasmy has been provided by the use of real-time quantitative PCR (qPCR) based on allelic refractory mutation detection system (ARMS-qPCR). Herein, we report an ARMS-qPCR assay for quantification of heteroplasmy using heteroplasmic mice with mtDNA of NZB/BINJ and C57BL/6 origin. Heteroplasmy and mtDNA copy number were estimated in germline and somatic tissues, providing evidence of the reliability of the approach. Furthermore, it enabled single-step quantification of heteroplasmy, with sensitivity to detect as low as 0.1% of either NZB/BINJ or C57BL/6 mtDNA. These findings are relevant as the ARMS-qPCR assay reported here is fully compatible with similar heteroplasmic mouse models used to study mitochondrial inheritance in mammals. PMID- 26274501 TI - Progressive Hemorrhage and Myotoxicity Induced by Echis carinatus Venom in Murine Model: Neutralization by Inhibitor Cocktail of N,N,N',N'-Tetrakis (2 Pyridylmethyl) Ethane-1,2-Diamine and Silymarin. AB - Viperbite is often associated with severe local toxicity, including progressive hemorrhage and myotoxicity, persistent even after the administration of anti snake venom (ASV). In the recent past, investigations have revealed the orchestrated actions of Zn2+ metalloproteases (Zn2+MPs), phospholipase A2s (PLA2s) and hyaluronidases (HYs) in the onset and progression of local toxicity from the bitten site. As a consequence, venom researchers and medical practitioners are in deliberate quest of potent molecules alongside ASV to tackle the brutal local manifestations induced by aforesaid venom toxins. Based on these facts, we have demonstrated the protective efficacy of inhibitor cocktail containing equal ratios of N,N,N',N'-tetrakis (2-pyridylmethyl) ethane-1,2 diamine (TPEN) and silymarin (SLN) against progressive local toxicity induced by Echis carinatus venom (ECV). In our previous study we have shown the inhibitory potentials of TPEN towards Zn2+MPs of ECV (IC50: 6.7 MUM). In this study we have evaluated in vitro inhibitory potentials of SLN towards PLA2s (IC50: 12.5 MUM) and HYs (IC50: 8 MUM) of ECV in addition to docking studies. Further, we have demonstrated the protection of ECV induced local toxicity with 10 mM inhibitor cocktail following 15, 30 min (for hemorrhage and myotoxicity); 60 min (for hemorrhage alone) of ECV injection in murine model. The histological examination of skin and thigh muscle sections taken out from the site of ECV injection substantiated the overall protection offered by inhibitor cocktail. In conclusion, the protective efficacy of inhibitor cocktail is of high interest and can be administered locally alongside ASV to treat severe local toxicity. PMID- 26274502 TI - Molecular Basis for the Mechanism of Constitutive CBP/p300 Coactivator Recruitment by CRTC1-MAML2 and Its Implications in cAMP Signaling. AB - The cyclic AMP response element-binding protein (CREB) is a signal-dependent transcription factor that exerts its positive effects on gene transcription of a broad range of genes by recruiting coactivators, including CREB-binding protein (CBP), its paralog, p300, and the family of CRTC (CREB-regulated transcriptional coactivators) proteins. Whereas recruitment of CBP/p300 is dependent on CREB phosphorylation at Ser133, recruitment of CRTCs is not. Here we describe how both mechanisms could concurrently drive transcription of CREB targets in a subset of head and neck cancers featuring chromosomal translocations that fuse portions of CRTC1 and CRTC3 genes with that of the Mastermind-like transcriptional coactivator MAML2. We show that a peptide derived from transactivation domain 1 (TAD1) of MAML2 binds to the CBP KIX domain with micromolar affinity. An ~20 residue segment within this peptide, conserved in MAML2 orthologs and paralogs, binds directly to a KIX surface previously shown to bind to MLL1. The 20-residue MAML2 segment shares sequence similarity with MLL1, especially at those positions in direct contact with KIX, and like MLL1, the segment is characterized by the presence of an ~10-residue helix. Because CRTC1/3-MAML2 fusion proteins are constitutively nuclear, like CREB, our results suggest constitutive recruitment of CBP/p300 to CREB targets that could be further enhanced by signals that cause CREB Ser133 phosphorylation. PMID- 26274503 TI - Comparative MiRNA Expressional Profiles and Molecular Networks in Human Small Bowel Tissues of Necrotizing Enterocolitis and Spontaneous Intestinal Perforation. AB - BACKGROUND: Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are acute intestinal conditions which could result in mortality and severe morbidity in preterm infants. Our objective was to identify dysregulated micro-RNAs (miRNAs) in small bowel tissues of NEC and SIP, and their possible roles in disease pathophysiology. METHODS: We performed differential miRNA arrays on tissues of NEC (n = 4), SIP (n = 4) and surgical-control (Surg CTL; n = 4), and validated target miRNAs by qPCR (n = 10 each group). The association of target miRNAs with 52 dysregulated mRNAs was investigated by bioinformatics on functional and base-pair sequence algorithms, and correlation in same tissue samples. RESULTS: We presented the first miRNA profiles of NEC, SIP and Surg-CTL intestinal tissues in preterm infants. Of 28 validated miRNAs, 21 were significantly different between NEC or SIP and Surg-CTL. Limited overlapping in the aberrant expression of miRNAs between NEC and SIP indicated their distinct molecular mechanisms. A proposed network of dysregulated miRNA/mRNA pairs in NEC suggested interaction at bacterial receptor TLR4 (miR-31, miR-451, miR-203, miR-4793-3p), mediated via key transcription factors NFKB2 (miR 203), AP-1/FOSL1 (miR-194-3p), FOXA1 (miR-21-3p, miR-431 and miR-1290) and HIF1A (miR-31), and extended downstream to pathways of angiogenesis, arginine metabolism, cell adhesion and chemotaxis, extracellular matrix remodeling, hypoxia/oxidative stress, inflammation and muscle contraction. In contrast, upregulation of miR-451 and miR-223 in SIP suggested modulation of G-protein mediated muscle contraction. CONCLUSIONS: The robust response of miRNA dysregulation in NEC and SIP, and concerted involvement of specific miRNAs in the molecular networks indicated their crucial roles in mucosa integrity and disease pathophysiology. PMID- 26274504 TI - Correlations between Clinical Features and Mortality in Patients with Vibrio vulnificus Infection. AB - Vibrio vulnificus is a common gram-negative bacterium, which might cause morbidity and mortality in patients following consumption of seafood or exposure to seawater in Southeast China. We retrospectively analyzed clinical data of patients with laboratory confirmed V. vulnificus infection. Twenty one patients were divided into a survival group and a non-surviving (or death) group according to their clinical outcome. Clinical data and measurements were statistically analyzed. Four patients (19.05%) died and five patients gave positive cultures from bile fluid, and 16 other patients gave positive culture from blood or blisters. Ten patients (47.62%) had an underlying liver disease and marine related events were found in sixteen patients (76.2%). Patients with heavy drinking habits might be at increased mortality (p = 0.028). Clinical manifestations of cellulitis (47.6%), septic shock (42.9%) and multiple organ failure (28.6%) were statistically significant when comparing survivors and non survivors (p = 0.035, p = 0.021 and p = 0.003, respectively). The laboratory results, including hemoglobin < 9.0 g/L (p = 0.012), platelets < 2.0 * 109 /L, prothrombin time activity (PTA) <20%, decreased serum creatinine and increased urea nitrogen were statistically significant (p = 0.012, p = 0.003, p = 0.028 and p = 0.028, respectively). Patients may be at a higher risk of mortality under situations where they have a history of habitual heavy alcoholic drink consumption (p = 0.028, OR = 22.5, 95%CI 1.5-335.3), accompanied with cellulitis, shock, multiple organ failure, and laboratory examinations that are complicated by decreased platelets, hemoglobin and significantly prolonged prothrombin time (PT). PMID- 26274506 TI - Organ Allocation and Distribution: Lessons to Be Learned and Principles to Lead Us Forward. PMID- 26274505 TI - Circular RNA of the human sphingomyelin synthase 1 gene: Multiple splice variants, evolutionary conservatism and expression in different tissues. AB - The human sphingomyelin synthase 1 gene (SGMS1) encodes an essential enzyme that is involved in the synthesis of sphingomyelin and diacylglycerol from phosphatidylcholine and ceramide. Among the products of SGMS1, we found new transcripts, circular RNAs (circRNAs), that contain sequences of the gene's 5' untranslated region (5'UTR). Some of them include the gene's coding region and fragments of introns. An analysis of the abundance of circRNAs in human tissues showed that the largest transcripts were predominantly found in different parts of the brain. circRNAs of rat and mouse sphingomyelin synthase 1 orthologous genes were detected and are highly similar to the human SGMS1 gene transcripts. A quantitative analysis of the abundance of such transcripts also revealed their elevated amount in the brain. A computational analysis of sequences of human circRNAs showed their high potential of binding microRNAs (miRNAs), including the miRNAs that form complexes with Ago proteins and the mRNA of SGMS1. We assume that the circRNAs identified here participate in the regulation of the function of the SGMS1 gene in the brain. PMID- 26274507 TI - An Isolable, Photoswitchable N-Heterocyclic Carbene: On-Demand Reversible Ammonia Activation. AB - The first isolable, photoswitchable N-heterocyclic carbene was synthesized and found to undergo reversible electrocyclic isomerization upon successive exposure to UV and visible radiation. The UV-induced ring closure afforded substantial changes to the electronic structure of the dithienylethene-based NHC, as evidenced by changes in the corresponding UV/Vis absorption and (13)C NMR spectra. Likewise, molecular orbital calculations revealed diminished electron density at the carbene nucleus upon photocyclization, consistent with the enhanced electrophilicity displayed by the ring-closed form. The photoswitchable NHC was successfully switched between its ring-opened and ring-closed states with high fidelity over multiple cycles. Furthermore, the ring-closed isomer was found to undergo facile N-H bond activation, allowing for the controlled capture and release of ammonia upon cycling between its isomeric states. PMID- 26274508 TI - High-quality results of cytoreductive surgery and heated intraperitoneal chemotherapy perfusion for carcinomatosis at a low volume institution. AB - BACKGROUND AND OBJECTIVES: Maximal cytoreductive surgery (CS) with heated intraperitoneal chemotherapy perfusion (HIPEC) for peritoneal carcinomatosis can improve oncologic outcomes, but is associated with significant morbidity. Whether low-volume experience with CS/HIPEC results in acceptable outcomes is unknown. METHODS: A retrospective review of all patients undergoing CS/HIPEC by a single surgeon. Experience was divided into first versus second 50 cases, and patient characteristics, operative details, and outcomes were compared. RESULTS: Ninety patients underwent 100 CS/HIPEC procedures (mean age 57 years, 68% female). Compared to the initial experience, the second 50 cases included more high grade tumors (68 vs. 52%) and greater disease burden (PCI 14.2 vs. 12.4). Operative times remained unchanged and mean blood loss decreased (978 vs. 684 ml). Hospital stay (mean 18.1 vs. 12.6 days), major complications (24 vs. 16%), and perioperative mortality (8 vs. 2%) declined. Overall median survival was 18 months and was longer with low grade tumors (26 vs. 16 months, P = 0.03). CONCLUSIONS: Patients experienced reduced EBL, fewer major complications, and shorter hospital stay, despite having higher disease burden and higher grade tumors. This suggests that even low-volume experience with CS/HIPEC can lead to a trend in reduction of adverse perioperative events with acceptable oncologic outcomes. PMID- 26274510 TI - In response to the article, "Relationship of Adverse Events and Support to RN Burnout". PMID- 26274509 TI - Gain-of-function nature of Cav1.4 L-type calcium channels alters firing properties of mouse retinal ganglion cells. AB - Proper function of Cav1.4 L-type calcium channels is crucial for neurotransmitter release in the retina. Our understanding about how different levels of Cav1.4 channel activity affect retinal function is still limited. In the gain-of function mouse model Cav1.4-IT we expected a reduction in the photoreceptor dynamic range but still transmission toward retinal ganglion cells. A fraction of Cav1.4-IT ganglion cells responded to light stimulation in multielectrode array recordings from whole-mounted retinas, but showed a significantly delayed response onset. Another significant number of cells showed higher activity in darkness. In addition to structural remodeling observed at the first retinal synapse of Cav1.4-IT mice the functional data suggested a loss of contrast enhancement, a fundamental feature of our visual system. In fact, Cav1.4-IT mouse retinas showed a decline in spatial response and changes in their contrast sensitivity profile. Photoreceptor degeneration was obvious from the nodular structure of cone axons and enlarged pedicles which partly moved toward the outer nuclear layer. Loss of photoreceptors was also expressed as reduced expression of proteins involved in chemical and electrical transmission, as such metabotropic glutamate receptor mGluR6 and the gap junction protein Connexin 36. Such gross changes in retinal structure and function could also explain the diminished visual performance of CSNB2 patients. The expression pattern of the plasma membrane calcium ATPase 1 which participates in the maintenance of the intracellular calcium homeostasis in photoreceptors was changed in Cav1.4-IT mice. This might be part of a protection mechanism against increased calcium influx, as this is suggested for Cav1.4-IT channels. PMID- 26274511 TI - Better Care, Better Quality: Reducing Avoidable Hospitalizations of Nursing Home Residents. PMID- 26274512 TI - Creating a Standardized Process to Meet Core Measure Compliance. AB - A standardized process to improve compliance with venous thromboembolism prophylaxis and hospital-based inpatient psychiatric services Core Measures was developed, implemented, and evaluated by a clinical nurse specialist team. The use of a 1-page tool with the requirements and supporting evidence, combined with concurrent data and feedback, ensured success of improving compliance. The initial robust process of education and concurrent and retrospective review follow-up allowed for this process to be successful. PMID- 26274513 TI - Solvatochromism, Reversible Chromism and Self-Assembly Effects of Heteroatom Assisted Aggregation-Induced Enhanced Emission (AIEE) Compounds. AB - Two compounds, 9,10-bis[2-(quinolyl)vinyl]anthracene (BQVA) and 9,10-bis[2 (naphthalen-2-yl)vinyl]anthracene (BNVA), have been synthesised and investigated. Both of them have aggregation-induced enhanced emission (AIEE) properties. Heteroatom-assisted BQVA shows solvatochromism, reversible chromism properties and self-assembly effects. When increasing the solvent polarities, the green solution of BQVA turns to orange with a redshift of the fluorescence emission wavelengths from lambda=527 to 565 nm. Notably, BQVA exhibits reversible chromism properties, including mechano- and thermochromism. The as-prepared BQVA powders show green fluorescence (lambdaem=525 nm) and the colour can turn into orange (lambdaem=573 nm) after grinding. Interestingly, the orange colour can return at high temperature. Based on these reversible chromism properties, a simple and convenient erasable board has been designed. Different from BQVA, non-heteroatom assisted BNVA has no clear chromic processes. The results obtained from XRD, differential scanning calorimetry, single-crystal analysis and theoretical calculations indicate that the chromic processes depend on the heteroatoms in BQVA. Additionally, BQVA also exhibits excellent self-assembly effects in different solvents. Homogeneous nanospheres are formed in mixtures of tetrahydrofuran and water, which are then doped into silica nanoparticles and treated with 3-aminopropyltriethoxysilane to give amino-functionalised nanoparticles (BQVA-AFNPs). The BQVA?AFNPs could be used to stain protein markers in polyacrylamide gel electrophoresis. PMID- 26274514 TI - Author's response re: Finazzi-Agro E. Prevalence of "uncomplicated" stress urinary incontinence in female patients prior to surgery. Neurourol Urodyn 2015. PMID- 26274515 TI - Overgeneral past and future thinking in dysphoria: the role of emotional cues and cueing methodology. AB - Overgeneral memory, where individuals exhibit difficulties in retrieving specific episodes from autobiographical memory, has been consistently linked with emotional disorders. However, the majority of this literature has relied upon a single methodology, in which participants respond to emotional cue words with explicit instructions to retrieve/simulate specific events. Through the use of sentence completion tasks the current studies explored whether overgenerality represents a habitual pattern of thinking that extends to how individuals naturally consider their personal past and future life story. In both studies, when compared with controls, dysphoric individuals evidenced overgeneral thinking style with respect to their personal past. However, overgeneral future thinking was only evident when the sentence stems included emotional words. These findings highlight the importance of investigating the overgenerality phenomenon using a variety of cueing techniques and results are discussed with reference to the previous literature exploring overgenerality and cognitive models of depression. PMID- 26274516 TI - Clinical Outcomes After Implantation of a Trifocal Toric Intraocular Lens. AB - PURPOSE: To evaluate the visual, refractive, and contrast sensitivity outcomes, as well as the level of photic phenomena, after cataract surgery with implantation of a trifocal diffractive toric intraocular lens (IOL). METHODS: This prospective study included 56 eyes with corneal astigmatism of 1.00 diopters (D) or greater of 28 patients (age: 23 to 78 years) undergoing cataract surgery with implantation of the trifocal toric IOL AT LISA tri toric 939MP (Carl Zeiss Meditec, Jena, Germany). Monocular and binocular visual outcomes, refractive changes, contrast sensitivity, and photic phenomena perception (Halo & Glare Simulator; Eyeland-Design Network GmbH, Vreden, Germany) were evaluated at 3 months postoperatively. RESULTS: Mean 3-month postoperative monocular uncorrected distance (UDVA), intermediate (UIVA), and near (UNVA) visual acuities were 0.13+/ 0.15, 0.08+/-0.15, and 0.13+/-0.18 logMAR, respectively. Binocular postoperative CDVA, DCIVA, and DCNVA values were 0.10 logMAR or better in all cases. A total of 88.2%, 88.2%, and 95.5% of eyes achieved binocular UDVA, UIVA, and UNVA values of 0.20 logMAR or better, respectively. Postoperative refractive cylinder was 0.50 D or less and 1.00 D or less in 78.6% and 98.2% of eyes, respectively. Photopic contrast sensitivity was significantly better than mesopic values for the spatial frequencies of 6 (P=.007), 12 (P=.005), and 18 cycles/degree (P=.011). Mean size and intensity of halos were 50.67+/-15.69 and 54.89+/-17.86, respectively. Mean glare size and intensity were 39.67+/-3.51 and 44.67+/-15.01, respectively. CONCLUSIONS: The evaluated trifocal diffractive toric IOL provides an effective restoration of the distance, intermediate, and near vision after cataract surgery with good levels of visual quality and minimal photic phenomena. PMID- 26274517 TI - Vector Analysis, Rotational Stability, and Visual Outcome After Implantation of a New Aspheric Toric IOL. AB - PURPOSE: To evaluate vector analysis, rotational stability, and refractive and visual outcome of a new toric intraocular lens (IOL) for correction of preexisting corneal astigmatism during routine cataract surgery. METHODS: In this prospective, interventional case series, 30 toric, aspheric Bi-Flex T toric IOLs (Medicontur Medical Engineering Ltd., Inc., Zsambek, Hungary) were implanted in 20 consecutive patients with topographic corneal astigmatism between 1.50 and 4.00 diopters (D) and evaluated within the first year after implantation. Appropriate IOL-toric alignment was facilitated by combined imaging/eye tracking technology. Postoperative evaluation included refraction and uncorrected and corrected distance visual acuities (UDVA, CDVA). For each visit, photodocumentation in retroillumination was performed to evaluate toric alignment and potential toric IOL rotation. Vector analysis of refractive astigmatism was performed using the Alpins method. RESULTS: At 12 months postoperatively, a reduction of the refractive astigmatism from 1.93+/-0.90 D (range: 0.50 to 4.00 D) to 0.28+/-0.61 D (range: 0.00 to 1.50 D) could be found, with patients achieving a mean UDVA of 0.06+/-0.16 logMAR (range: -0.18 to 0.40 logMAR; Snellen 20/20). Intraoperative to 12-month postoperative comparison of IOL axis alignment showed low levels of rotation (0.2 degrees +/-2.41 degrees ; range: +4 degrees to -5 degrees ). Vector analysis showed target induced astigmatism of 0.60 D @180 degrees , surgically induced astigmatism of 0.80 D @177 degrees , correction index of 1.02+/-0.25, and a difference vector of 0.30 D @82 degrees . CONCLUSIONS: Implantation of the new Bi-Flex T IOL was a safe, stable, and effective method to correct preexisting regular corneal astigmatism during cataract surgery. PMID- 26274518 TI - The Contested Terrain of Focus Groups, Lived Experience, and Qualitative Research Traditions. PMID- 26274519 TI - Methylmercury biomagnification in an Arctic pelagic food web. AB - Mercury (Hg) is a toxic element that enters the biosphere from natural and anthropogenic sources, and emitted gaseous Hg enters the Arctic from lower latitudes by long-range transport. In aquatic systems, anoxic conditions favor the bacterial transformation of inorganic Hg to methylmercury (MeHg), which has a greater potential for bioaccumulation than inorganic Hg and is the most toxic form of Hg. The main objective of the present study was to quantify the biomagnification of MeHg in a marine pelagic food web, comprising species of zooplankton, fish, and seabirds, from the Kongsfjorden system (Svalbard, Norway), by use of trophic magnification factors. As expected, tissue concentrations of MeHg increased with increasing trophic level in the food web, though at greater rates than observed in several earlier studies, especially at lower latitudes. There was strong correlation between MeHg and total Hg concentrations through the food web as a whole. The concentration of MeHg in kittiwake decreased from May to October, contributing to seasonal differences in trophic magnification factors. The ecology and physiology of the species comprising the food web in question may have a large influence on the magnitude of the biomagnification. A significant linear relationship was also observed between concentrations of selenium and total Hg in birds but not in zooplankton, suggesting the importance of selenium in Hg detoxification for individuals with high Hg concentrations. PMID- 26274522 TI - Isolation of Neofusicoccum parvum from withered grapes: strain characterization, pathogenicity and its detrimental effects on passito wine aroma. AB - AIMS: There is scarce information on the occurrence of several fungi that infect withered grapes to produce passito wine. Isolation and characterization of Neofusicoccum parvum strains and evaluation of their effects on withered grape and wine were carried out. METHODS AND RESULTS: Nine isolates were phenotypically characterized by colony morphology and genetically discriminated by molecular methods. Two representative strains were identified as N. parvum according to the phylogenetic analysis of internal transcribed spacer (ITS), and a part of translation elongation factor 1-alfa (TEF) and beta-tubulin DNA sequences. The pathogenicity of both strains on grape berries varied according to the inoculation and incubation conditions. Under withering conditions, infected berries showed browning and shrivelling and some berries showed pycnidial development on the surface. The infection affected laccase, esterase, beta glucosidase and tannase on grape juice as well as the content of several aroma molecules on resulting wines. Strain-specific effects on wine composition were also observed. CONCLUSIONS: Neofusicoccum parvum occurred in withered grapes and was able to infect grapes under withering condition changing the aroma wine. SIGNIFICANCE AND IMPACT OF THE STUDY: This study reports for the first time the N. parvum isolation in fruit-drying rooms and indicates its important role on postharvest grape infection. PMID- 26274523 TI - Cell-free expression of functional receptor tyrosine kinases. AB - Receptor tyrosine kinases (RTKs) play critical roles in physiological and pathological processes, and are important anticancer drug targets. In vitro mechanistic and drug discovery studies of full-length RTKs require protein that is both fully functional and free from contaminating proteins. Here we describe a rapid cell-free and detergent-free co-translation method for producing full length and functional ERBB2 and EGFR receptor tyrosine kinases supported by water soluble apolipoprotein A-I based nanolipoprotein particles. PMID- 26274524 TI - Association Between BMP-2 and Carcinogenicity. AB - STUDY DESIGN: Literature review. OBJECTIVE: To evaluate the association between recombinant human bone morphogenetic protein-2 (rhBMP-2) and malignancy. SUMMARY OF BACKGROUND DATA: The use of rhBMP-2 in spine surgery has been the topic of much debate as studies assessing the association between rhBMP-2 and malignancy have come to conflicting conclusions. METHODS: A systematic review of the literature was performed using the PubMed-National Library of Medicine/National Institute of Health databases. Only non-clinical studies directly addressing BMP 2 and cancer were included. Articles were categorized by study type (animal, in vitro cell line/human/animal), primary malignancy, cancer attributes, and whether BMP-2 was pro-malignancy or not. RESULTS: A total of 4,131 articles were reviewed. Of those, 515 articles made reference to both BMP-2 and cancer, 99 of which were found to directly examine the role of BMP-2 in cancer. Seventy-five studies were in vitro and 24 were animal studies. Forty-three studies concluded that BMP-2 enhanced cancer function, whereas 18 studies found that BMP-2 suppressed malignancy. Thirty-six studies did not examine whether BMP-2 enhanced or suppressed cancer function. Fifteen studies demonstrated BMP-2 dose dependence (9 enhancement, 6 suppression) and one study demonstrated no dose dependence. Nine studies demonstrated BMP-2 time dependence (6 enhancement, 3 suppression). However, no study demonstrated that BMP-2 caused cancer de novo. CONCLUSION: Currently, conflicting data exist with regard to the effect of exogenous BMP-2 on cancer. The majority of studies addressed the role of BMP-2 in prostate (17%), breast (17%), and lung (15%) cancers. Most were in vitro studies (75%) and examined cancer invasiveness and metastatic potential (37%). Of 99 studies, there was no demonstration of BMP-2 causing cancer de novo. However, 43% of studies suggested that BMP-2 enhances tumor function, motivating more definitive research on the topic that also includes clinically meaningful dose- and time-dependence. LEVEL OF EVIDENCE: 2. PMID- 26274525 TI - Rationale for the Surgical Treatment of Lumbar Degenerative Spondylolisthesis. AB - STUDY DESIGN: A questionnaire survey. OBJECTIVE: The aim of this study was to determine the effect of patient age, dynamic instability, and/or low back pain on the treatment of patients with a degenerative spondylolisthesis, and if the operative approach is affected by surgeon specialty, location, or practice model. SUMMARY OF BACKGROUND DATA: The classic treatment for patients with symptomatic degenerative spondylolisthesis is decompression and fusion; however in a select group of patients, an isolated decompression may be reasonable. METHODS: A survey was sent to surgeon members of the Lumbar Spine Research Society and AOSpine requesting information regarding their preferred treatment of degenerative spondylolisthesis for a number of different clinical scenarios. Determinants included patient age, the presence of instability, symptoms of low back pain, surgeon's location, surgeon's specialty, and practice model. RESULTS: A total of 223 spine surgeons completed the survey. Age of the patient, the presence of instability, and low back pain all significantly (P < 0.0001) affected the recommended treatment, which were independent of surgeon factors. Older patients were significantly less likely to be offered an interbody fusion and more likely to be recommended for an isolated decompression (P < 0.0001), and the presence of dynamic instability made an interbody fusion more likely than an isolated decompression (P < 0.0001). Of those who responded, 53.2% of surgeons reported they would recommend an isolated decompression for a properly selected patient with a degenerative spondylolisthesis. CONCLUSION: The most common operative treatment for a degenerative spondylolisthesis is a decompression and fusion; however, the results of this survey demonstrate that surgeons consider degenerative spondylolisthesis a heterogeneous condition that requires an individualized surgical plan. Future studies are needed to evaluate the effect of variables such as age, the presence of low back pain, and the presence of dynamic instability on patient reported outcomes from various surgical options. LEVEL OF EVIDENCE: N/A. PMID- 26274526 TI - Geographic Variation in Early MRI for Acute Work-Related Low Back Pain and Associated Factors. AB - STUDY DESIGN: Retrospective cohort study using medical claims data. OBJECTIVE: To document the extent of geographic variation in utilization of magnetic resonance imaging (MRI) for working-age patients early in the course of acute, disabling low back pain (LBP); to identify potential factors associated with the most extreme variations. SUMMARY OF BACKGROUND DATA: Although guidelines discourage MRI in acute uncomplicated LBP, this practice is highly prevalent. Geographic variation in radiologic testing is common, and may indicate problems with access or quality of care, yet this has not been studied in working-age patients with LBP (a frequent cause for acute care visits). METHODS: All cases of acute, disabling LBP with onset between 1/1/2002 and 12/31/2007 were selected from a large workers' compensation data source. Detailed information from medical bills was used to identify persons who received early MRI (within 30 days of onset), classify cases by LBP severity, and exclude those with concurrent injuries or diseases, and/or prior LBP disability. Individual predictors included age, gender, job tenure, and industry. State-level predictors included economic, physician supply and practice variables, workers compensation system features, and MRI testing location. Generalized linear mixed models were constructed to evaluate within- and between-state variability, selecting the six highest and six lowest MRI utilization states. RESULTS: State rates of early MRI scanning varied from 6.0% to 58.4%. In the 12 selected most extreme states, non-hospital MRI sites and lower state median income were associated with higher rates of early MRIs, explaining 84% of between-state variation, and 12.5% of all observed variability. Inter-state differences in MRI rates were greatest for lower severity cases. Higher severity diagnoses were more common in high utilization states. CONCLUSIONS: Between-state inappropriate early MRI variability is largely explained by rate of non-hospital MRI sites and state median income. Potential solutions include efforts to address inappropriate referral patterns based on private MRI facility ownership, and to improve quality of communication with low income patients. LEVEL OF EVIDENCE: 4. PMID- 26274527 TI - Does Lumbosacral Transitional Vertebra Have Any Influence on Sacral Tilt? AB - STUDY DESIGN: Retrospective case-control study. OBJECTIVE: To compare the sacral tilt (ST) angle between patients with and without lumbosacral transitional vertebra (LSTV). SUMMARY OF BACKGROUND DATA: Although LSTV is a common malformation of the lumbosacral region, data regarding the effect of LSTV on the tilt of sacrum is limited. METHODS: Anterioposterior and lateral lumbar radiographs of patients with low back pain performed between March 2013 and September 2013 were extracted from the medical electronic database. Among these radiographs, those belonging to patients with Castellvi types II, III, and IV LSTV were identified. The angle of ST was measured on lateral lumbar radiographs and compared with that of age- and sex-matched controls without LSTV. RESULTS: Of the 1588 radiographs extracted from the database, 96 (6.1%) were positive in terms of Castellvi types II, III and IV LSTV. 85 of them were found to be eligible for analysis. Patients with LSTV had significantly smaller ST angle than those without LSTV (p = 0.000). However, this angle did not differ among types (II, III and IV) of LSTV (p = 0.788). CONCLUSION: Results of this study revealed that patients with LSTV had less ST--that is to say more vertical sacrum-than those without this malformation. LEVEL OF EVIDENCE: 4. PMID- 26274528 TI - Reduced Field-of-View Diffusion Tensor Imaging of the Spinal Cord Shows Motor Dysfunction of the Lower Extremities in Patients With Cervical Compression Myelopathy. AB - STUDY DESIGN: A cross-sectional study. OBJECTIVE: The aim of this study was to quantify spinal cord dysfunction at the tract level in patients with cervical compressive myelopathy (CCM) using reduced field-of-view (rFOV) diffusion tensor imaging (DTI). SUMMARY OF BACKGROUND DATA: Although magnetic resonance imaging (MRI) is the standard used for radiological evaluation of CCM, information acquired by MRI does not necessarily reflect the severity of spinal cord disorder. There is a growing interest in developing imaging methods to quantify spinal cord dysfunction. To acquire high-resolution DTI, a new scheme using rFOV has been proposed. METHODS: We enrolled 10 healthy volunteers and 20 patients with CCM in this study. The participants were studied using a 3.0-T MRI system. For DTI acquisitions, diffusion-weighted spin-echo rFOV single-shot echo-planar imaging was used. Regions-of-interest (ROI) for the lateral column (LC) and posterior column (PC) tracts were determined on the basis of a map of fractional anisotropy (FA) of the spinal cord and FA values were measured. The FA of patients with CCM was compared with that of healthy controls and correlated with Japanese Orthopaedic Association (JOA) score. RESULTS: In LC and PC tracts, FA values in patients with CCM were significantly lower than in healthy volunteers. Total JOA scores correlated moderately with FA in LC and PC tracts. JOA subscores for motor dysfunction of the lower extremities correlated strongly with FA in LC and PC tracts. CONCLUSION: It is feasible to evaluate the cervical spinal cord at the tract level using rFOV DTI. Although FA values at the maximum compression level were not well correlated with total JOA scores, they were strongly correlated with JOA subscores for motor dysfunction of the lower extremities. Our findings suggest that FA reflects white matter dysfunction below the maximum compression level and FA can be used as an imaging biomarker of spinal cord dysfunction. LEVEL OF EVIDENCE: 4. PMID- 26274529 TI - What Is the Clinical Relevance of Radiographic Nonunion After Single-Level Lumbar Interbody Arthrodesis in Degenerative Disc Disease?: A Meta-Analysis of the YODA Project Database. AB - STUDY DESIGN: Meta-analysis of 4 randomized controlled clinical trials (RCTs). OBJECTIVE: The aim of the study was to determine if patients with degenerative disc disease who achieve radiographic fusion after single-level lumbar interbody arthrodesis have better clinical outcomes than patients with radiographic pseudarthrosis at 12 and 24 months postoperative. SUMMARY OF BACKGROUND DATA: The clinical relevance of successful fusion after lumbar arthrodesis with recombinant human bone morphogenetic protein-2 or iliac crest bone autograft has recently been questioned in the literature. METHODS: Individual patient-level data of 4 RCTs were obtained from the Yale University Open Data Access Project project and analyzed. Clinical outcomes (Oswestry Disability Index [ODI]; Numeric Rating Scales [NRSs] for back and leg pain) were compared between patients with radiographically confirmed fusion and those with radiographic nonunion 1 and 2 years postoperative. The results of each study were first analyzed separately, and then were pooled by meta-analysis. The GRADE approach was applied to evaluate the level of evidence. RESULTS: A total of 496 patients with clinical and radiographic data at 1- and 2-year follow-ups were identified. Of these, 5.5% (95% confidence interval: 3.7; 8.3) had radiographic nonunion which did not require reoperation. Patients with fusion had better improvements in ODI (P < 0.001) and NRS back pain scores (P < 0.001). The overall percentage of fused patients with ODI and NRS back pain scores that exceeded the criteria for minimal clinically important differences was also significantly higher than that of patients with nonunion (ODI, odds ratio [OR] = 2.7, P = 0.019; NRS back pain, OR = 3.5, P = 0.033). The predictive values of fusion for clinical outcomes, however, were poor, with low specificity and low negative predictive values. CONCLUSION: The presence of radiographic fusion is clinically significant, as patients with fusion had better clinical outcomes at 1 and 2 years postoperative than those with nonunion; however, patient-centered clinical outcomes should also be taken into consideration as independent, complimentary variables when assessing treatment success. PMID- 26274530 TI - Electrochemotherapy to Metastatic Spinal Melanoma: A Novel Treatment of Spinal Metastasis? AB - STUDY DESIGN: Preliminary report of new antitumor treatment. OBJECTIVE: To evaluate the effectiveness of electrochemotherapy as a novel treatment of spinal metastasis. SUMMARY OF BACKGROUND DATA: Electrochemotherapy is a new antitumor treatment that combines systemic bleomycin with electric pulses delivered locally at the tumor site. These electric pulses permeabilize cell membranes in the tissue, allow bleomycin delivery diffusion inside the cells, and increase bleomycin cytotoxicity. Previous clinical studies have demonstrated the effectiveness of electrochemotherapy in the treatment of several primary and metastatic solid tumors. METHODS: Treatment planning for electrode positioning and electrical pulse parameters was prepared for 4 needle electrodes. Mini-open surgery with a left L5 laminectomy was performed to introduce the eletrodes. The patient was treated according to the established Electrochemotherapy Protocol with Bleomycin. Clinical efficacy of electrochemotherapy was evaluated according to a visual analog scale of pain, Oswestry Disability Index 2.0, the Karnofsky Performance Scale, and Response Evaluation Criteria in Solid Tumors. RESULTS: The assessed follow-up period was 48 months after the electrochemotherapy procedure. Neither serious electrochemotherapy-related adverse events, nor bleomycin toxicity were reported. Overall improvement in pain according to Oswestry Disability Index 2.0 and Karnofsky Performance Scale outcomes was better. CONCLUSION: Our case represents, to our knowledge, the first one to test the potential role of electrochemotherapy as treatment of spinal metastasis. Electrochemotherapy allowed a successful treatment of metastatic spinal melanoma. However, we believe that there is a strong scientific rationale to support the potential utility of electrochemotherapy as a novel treatment of spinal metastasis, regardless of the histological types. LEVEL OF EVIDENCE: 5. PMID- 26274531 TI - 2015 ISSLS Presidential Address: From paternalism to shared decision making: and back? PMID- 26274532 TI - Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides. AB - The development of topical microbicide formulations for vaginal delivery to prevent HIV-2 sexual transmission is urgently needed. Second- and third generation polyanionic carbosilane dendrimers with a silicon atom core and 16 sulfonate (G2-S16), napthylsulfonate (G2-NS16) and sulphate (G3-Sh16) end-groups have shown potent and broad-spectrum anti-HIV-1 activity. However, their antiviral activity against HIV-2 and mode of action have not been probed. Cytotoxicity, anti-HIV-2, anti-sperm and antimicrobial activities of dendrimers were determined. Analysis of combined effects of triple combinations with tenofovir and raltegravir was performed by using CalcuSyn software. We also assessed the mode of antiviral action on the inhibition of HIV-2 infection through a panel of different in vitro antiviral assays: attachment, internalization in PBMCs, inactivation and cell-based fusion. Vaginal irritation and histological analysis in female BALB/c mice were evaluated. Our results suggest that G2-S16, G2-NS16 and G3-Sh16 exert anti-HIV-2 activity at an early stage of viral replication inactivating the virus, inhibiting cell-to-cell HIV-2 transmission, and blocking the binding of gp120 to CD4, and the HIV-2 entry. Triple combinations with tenofovir and raltegravir increased the anti-HIV-2 activity, consistent with synergistic interactions (CIwt: 0.33-0.66). No vaginal irritation was detected in BALB/c mice after two consecutive applications for 2 days with 3% G2-S16. Our results have clearly shown that G2-S16, G2-NS16 and G3 Sh16 have high potency against HIV-2 infection. The modes of action confirm their multifactorial and non-specific ability, suggesting that these dendrimers deserve further studies as potential candidate microbicides to prevent vaginal/rectal HIV 1/HIV-2 transmission in humans. PMID- 26274534 TI - Antianginal Agents for the Management of Stable Ischemic Heart Disease: A Review. AB - Antianginal medications are an important aspect of optimal medical therapy for the management of angina in patients with stable ischemic heart disease. The lack of a standardized definition of effective antianginal therapy and the lack of clear understanding of the underlying evidence have often been cited as reasons for the large variations in the use of these particular classes of pharmacologic agents in contemporary clinical practice. Hence, we performed a search of the PubMed database and identified published manuscripts examining the effect of common antianginal agents on improving anginal parameters and on important clinical outcomes such as mortality, myocardial infarction, and repeat revascularization from multiple large randomized, controlled trials, systematic reviews, meta-analyses, and outcomes data from observational studies in patients with stable ischemic heart disease. The most commonly used antianginal agents (beta-blockers, nitrates, calcium channel blockers, and ranolazine) demonstrated equivalent efficacy in improving patient reported ischemic symptoms and quantitative exercise parameters. With regards to mortality, beta-blockers are beneficial in the setting of depressed left ventricular systolic function. In contrast, recent evidence points toward the lack of similar benefit of beta blockers in patients with preserved systolic function, even in the setting of prior myocardial infarction. No survival benefit has been identified with the use of calcium channel blockers, nitrates, or ranolazine. Currently, guidance regarding objective measurement and up titration of antianginal therapy is missing. There is an unmet need for development of potentially novel and clinically relevant methodology to assess the intensity and/or efficacy of antianginal therapy. PMID- 26274535 TI - Treatment Options in Massive and Submassive Pulmonary Embolism. AB - Pulmonary embolism (PE) is a common cardiovascular condition that represents a spectrum of disorders with a gradient of increased risk of adverse outcomes. The U.S. Surgeon General estimated that approximately 100,000 to 180,000 PE-related deaths occur in the United States annually, and that PE is the most preventable cause of death among hospitalized patients. Risk stratification is critical to identify the patients who may benefit from advanced therapy. This review will provide an overview of PE pathophysiology, evidence-based risk stratification strategies for patients with acute PE, a summary of traditional and novel oral anticoagulant options, and an in-depth discussion on the utilization of advanced therapeutic options, including systemic fibrinolysis, catheter-based pharmacomechanical therapy, and surgical embolectomy. PMID- 26274536 TI - Highly sensitive cardiac troponin assays: a comprehensive review of their clinical utility. AB - Cardiovascular disease is a major source of morbidity and remains the leading cause of death in the United States. To evaluate patients with suspected cardiovascular disease, several laboratory markers of cardiac injury are available including creatinine kinase, creatinine kinase isoenzyme MB, myoglobin, and cardiac troponins (cTn) I and T. cTns have become the preferred marker of cardiac damage because they are highly sensitive and are almost completely cardiac specific. Recently, highly sensitive cTn (hs-cTn) assays were developed and have been used across the world to more quickly and accurately diagnose myocardial infarction. In the United States, these assays have not been U.S. Food and Drug Association approved for clinical practice and therefore are only being used for research purposes. Advancements have taken place over the years in diagnosing and treating cardiovascular disease, but predicting who will suffer future cardiovascular events still remains elusive. A comprehensive review of the literature was conducted to discover how new hs-cTn are being utilized throughout other parts of the world and what potential future use they may serve here in the United States. Major subject points discussed in this article include the prevalence of detectable troponins in the general population, the use of hs-cTn assays in diagnosing a myocardial infarction, determining prognosis in patients who have experienced an acute coronary syndrome and in patients with congestive heart failure, predicting future risk of cardiovascular events in patients with coronary heart disease, and its potential role as a screening tool in primary prevention. The implementation of hs-cTn testing in the United States may be very beneficial to patients; however, more research will need to be done to fully elucidate the potential use of hs-cTn in clinical practice. PMID- 26274537 TI - Transcatheter mitral valve replacement: design implications, potential pitfalls and outcomes assessment. AB - Transcatheter mitral valve replacement (TMVR) is an emerging new treatment option in patients with advanced mitral valve disease deemed a high or prohibitive risk for surgery. Designing an ideal TMVR device requires a detailed understanding of different mitral valve pathologies and the complex, dynamic anatomy and physiology of the mitral apparatus. This review aims to critically evaluate design implications in TMVR in the context of mitral valve disease, imaging prerequisites, procedural approaches, potential complications, and outcomes assessment. PMID- 26274539 TI - Stapled haemorrhoidopexy: is it time to move on? AB - Stapled haemorrhoidectomy was proposed as an 'ideal' solution for symptomatic haemorrhoids, with minimal postoperative pain, no perianal wound requiring postoperative wound care and a relatively short operative time. Some randomised controlled trials and reviews confirmed these findings, claiming that stapled haemorrhoidopexy is the most effective and safe procedure for haemorrhoids. However, there are increasing number of publications highlighting that the technique is associated with serious and life threatening complications. Maybe it is now the time to accept that stapled haemorrhoidopexy has done its role in directing our attention to the fact that modern surgical treatment of haemorrhoids should avoid excision of anorectal skin but should instead aim at treatment intervention above the dentate line. PMID- 26274538 TI - Non-Vitamin K Antagonist Oral Anticoagulants and Antiplatelet Therapy for Stroke Prevention in Patients With Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials. AB - Non-vitamin K antagonist oral anticoagulants (NOACs) are frequently used to prevent stroke in patients with atrial fibrillation. These patients are often also on aspirin or other antiplatelet agents. It is possible that treatment with both NOACs and aspirin or other antiplatelet drug may be effective in decreasing stroke, but data are sparse regarding the efficacy and safety of using both agents for stroke prevention. To address these issues, data were pooled from the 4 recent randomized, controlled trials of NOACs: apixaban, rivaroxaban, dabigatran, and edoxaban, which included 42,411 patients; 14,148 (33.4%) were also on aspirin or other antiplatelet drug. The number of thromboembolic events among participants on NOAC and aspirin/antiplatelet was compared with the number of events in patients on NOAC alone. Bleeding rates were also compared between those on NOAC + aspirin/antiplatelet and on NOAC alone. These results were compared with thromboembolic and bleeding events in the warfarin + aspirin/antiplatelet versus warfarin alone. No greater risk for thromboembolism was seen in patients on NOACs compared with patients on both NOACs and aspirin/antiplatelet drug. In this nonrandomized comparison, there was initially a signal toward higher thromboembolic rates among NOAC users also on aspirin/antiplatelet drugs (relative risk, 1.16; 95% confidence intervals, 1.05, 1.29) when compared with NOAC alone. This likely reflected the higher CHADS2 scores of those on aspirin/antiplatelet drugs. When the analysis was limited to studies that included aspirin rather than other antiplatelet drugs, no difference was seen for thromboembolic rates comparing dual therapy to NOAC alone (relative risk, 1.02; 95% confidence intervals, 0.90, 1.15). Higher rates of bleeding were seen with aspirin/antiplatelet drug in conjunction with NOAC. In this meta analysis and nonrandomized comparison of aspirin/antiplatelet users and nonusers also on anticoagulation, there was no additional benefit seen of anticoagulation and antiplatelet therapy for stroke prevention when compared with anticoagulation alone. There was, however, an increased risk of bleeding. Careful assessment of the indications for antiplatelet drugs in patients with atrial fibrillation who are also receiving oral anticoagulants is warranted, and future randomized comparisons are needed. PMID- 26274540 TI - Negative thermal expansion and anomalies of heat capacity of LuB50 at low temperatures. AB - Heat capacity and thermal expansion of LuB50 boride were experimentally studied in the 2-300 K temperature range. The data reveal an anomalous contribution to the heat capacity at low temperatures. The value of this contribution is proportional to the first degree of temperature. It was identified that this anomaly in heat capacity is caused by the effect of disorder in the LuB50 crystalline structure and it can be described in the soft atomic potential model (SAP). The parameters of the approximation were determined. The temperature dependence of LuB50 heat capacity in the whole temperature range was approximated by the sum of SAP contribution, Debye and two Einstein components. The parameters of SAP contribution for LuB50 were compared to the corresponding values for LuB66, which was studied earlier. Negative thermal expansion at low temperatures was experimentally observed for LuB50. The analysis of the experimental temperature dependence for the Gruneisen parameter of LuB50 suggested that the low-frequency oscillations, described in SAP mode, are responsible for the negative thermal expansion. Thus, the glasslike character of the behavior of LuB50 thermal characteristics at low temperatures was confirmed. PMID- 26274541 TI - Limbal Approach-Subretinal Injection of Viral Vectors for Gene Therapy in Mice Retinal Pigment Epithelium. AB - The eye is a small and enclosed organ which makes it an ideal target for gene therapy. Recently various strategies have been applied to gene therapy in retinopathies using non-viral and viral gene delivery to the retina and retinal pigment epithelium (RPE). Subretinal injection is the best approach to deliver viral vectors directly to RPE cells. Before the clinical trial of a gene therapy, it is inevitable to validate the efficacy of the therapy in animal models of various retinopathies. Thus, subretinal injection in mice becomes a fundamental technique for an ocular gene therapy. In this protocol, we provide the easy and replicable technique for subretinal injection of viral vectors to experimental mice. This technique is modified from the intravitreal injection, which is widely used technique in ophthalmology clinics. The representative results of RPE/choroid/scleral complex flat-mount will help to understand the efficacy of this technique and adjust the volume and titer of viral vectors for the extent of gene transduction. PMID- 26274546 TI - Nonlinear electro-osmosis of dilute non-adsorbing polymer solutions with low ionic strength. AB - Nonlinear electro-osmotic behaviour of dilute non-adsorbing polymer solutions with low salinity is investigated using Brownian dynamics simulations and a kinetic theory. In the Brownian simulations, the hydrodynamic interaction between the polymers and a no-slip wall is considered using the Rotne-Prager approximation of the Blake tensor. In a plug flow under a sufficiently strong applied electric field, the polymer migrates toward the bulk, forming a depletion layer thicker than the equilibrium one. Consequently, the electro-osmotic mobility increases nonlinearly with increasing electric field and becomes saturated. This nonlinear mobility does not depend qualitatively on the details of the rheological properties of the polymer solution. Analytical calculations using the kinetic theory for the same system quantitatively reproduce the results of the Brownian dynamics simulation well. PMID- 26274547 TI - Considerations for Identifying the Boundaries of Sustainable Performance. PMID- 26274549 TI - Prolonged Sitting and Endothelial Function: Methodological Considerations. PMID- 26274548 TI - Response. PMID- 26274550 TI - Response. PMID- 26274551 TI - Intraoperative Temperature Management Means More than Being Warm at the End of the Case. PMID- 26274552 TI - Direct Monitoring of Nucleotide Turnover in Human Cell Extracts and Cells by Fluorogenic ATP Analogs. AB - Nucleotides containing adenosine play pivotal roles in every living cell. Adenosine triphosphate (ATP), for example, is the universal energy currency, and ATP-consuming processes also contribute to posttranslational protein modifications. Nevertheless, detecting the turnover of adenosine nucleotides in the complex setting of a cell remains challenging. Here, we demonstrate the use of fluorogenic analogs of ATP and adenosine tetraphosphate to study nucleotide hydrolysis in lysates of human cell lines and in intact human cells. We found that the adenosine triphosphate analog is completely stable in lysates of human cell lines, whereas the adenosine tetraphosphate analog is rapidly turned over. The observed activity in human cell lysates can be assigned to a single enzyme, namely, the human diadenosine tetraphosphate hydrolase NudT2. Since NudT2 has been shown to be a prognostic factor for breast cancer, the adenosine tetraphosphate analog might contribute to a better understanding of its involvement in cancerogenesis and allow the straightforward screening for inhibitors. Studying hydrolysis of the analogs in intact cells, we found that electroporation is a suitable method to deliver nucleotide analogs into the cytoplasm and show that high FRET efficiencies can be detected directly after internalization. Time-dependent experiments reveal that adenosine triphosphate and tetraphosphate analogs are both processed in the cellular environment. This study demonstrates that these nucleotide analogs indeed bear the potential to be powerful tools for the exploration of nucleotide turnover in the context of whole cells. PMID- 26274553 TI - Influence of the strategies and biomechanical parameters on the capacity to handle balance perturbation: a numerical assessment. PMID- 26274554 TI - Cryosectioning Method for Microdissection of Murine Colonic Mucosa. AB - The colonic mucosal tissue provides a vital barrier to luminal antigens. This barrier is composed of a monolayer of simple columnar epithelial cells. The colonic epithelium is dynamically turned over and epithelial cells are generated in the stem cell containing crypts of Lieberkuhn. Progenitor cells produced in the crypt-bases migrate toward the luminal surface, undergoing a process of cellular differentiation before being shed into the gut lumen. In order to study these processes at the molecular level, we have developed a simple method for the microdissection of two spatially distinct regions of the colonic mucosa; the proliferative crypt zone, and the differentiated surface epithelial cells. Our objective is to isolate specific crypt and surface epithelial cell populations from mouse colonic mucosa for the isolation of RNA and protein. PMID- 26274555 TI - Atomically Traceable Nanostructure Fabrication. AB - Reducing the scale of etched nanostructures below the 10 nm range eventually will require an atomic scale understanding of the entire fabrication process being used in order to maintain exquisite control over both feature size and feature density. Here, we demonstrate a method for tracking atomically resolved and controlled structures from initial template definition through final nanostructure metrology, opening up a pathway for top-down atomic control over nanofabrication. Hydrogen depassivation lithography is the first step of the nanoscale fabrication process followed by selective atomic layer deposition of up to 2.8 nm of titania to make a nanoscale etch mask. Contrast with the background is shown, indicating different mechanisms for growth on the desired patterns and on the H passivated background. The patterns are then transferred into the bulk using reactive ion etching to form 20 nm tall nanostructures with linewidths down to ~6 nm. To illustrate the limitations of this process, arrays of holes and lines are fabricated. The various nanofabrication process steps are performed at disparate locations, so process integration is discussed. Related issues are discussed including using fiducial marks for finding nanostructures on a macroscopic sample and protecting the chemically reactive patterned Si(100)-H surface against degradation due to atmospheric exposure. PMID- 26274556 TI - [Pedicle Subtraction Osteotomy in the Lumbar Spine for Correction of Sagittal Spinal Imbalance]. AB - INTRODUCTION: A sagittal spinal deformity can lead to a significant reduction in quality of life. A loss of lumbar lordosis, which may be degenerative or iatrogenic, is usually identified as the main driver for a sagittal imbalance. Re lordosing the lumbar spine has the potential to correct a global sagittal imbalance. Different surgical techniques are available. The present video describes the pedicle subtraction osteotomy, which represents a powerful option for rigid and severe deformities. INDICATION: The pedicle subtraction osteotomy is most suitable for rigid deformities due to a lack of lumbar lordosis in which re-lordosing of 30 degrees or more is intended. This is often the case if the difference between lumbar lordosis and pelvic incidence exceeds 30 degrees . METHOD: The osteotomy begins with a wide laminectomy. The facet joints above and the pars interarticulares below the pedicles are removed. The pedicle is osteotomised in a wedge-shaped technique and resected while the dura and the exiting nerve root are protected with retractors. After resection of the posterior wall of the vertebral body, the osteotomy can be closed using the anterior wall of the vertebral body as pivot. CONCLUSION: The pedicle subtraction osteotomy represents a powerful surgical technique for correction of a sagittal spinal imbalance. PMID- 26274557 TI - [S3 Guideline. Part 1: Diagnosis and Differential Diagnosis of Non-Traumatic Adult Femoral Head Necrosis]. AB - Non-traumatic femoral head necrosis (FHN) is primarily a disease of the middle aged adult. Early diagnosis, at a time with lacking or minimal clinical symptoms, is mandatory to consider conservative therapy or joint preserving operations as a therapeutic option. The new German S3 guideline about diagnosis and therapy of FHN is a cooperative effort of five professional medical societies, overall headed by the Deutsche Gesellschaft fur Orthopadie und Orthopadische Chirurgie (DGOOC). This review (part I/III) cites and explains the statements of the S3 guideline as agreed on the use of imaging methods for diagnosis of FHN. A diagnostic algorithm is presented. FHN clinically has to be considered in case of equivocal pain of a hip joint with a minimum of 6 weeks duration, when risk factors can be revealed, groin pain at clinical investigation, limping, pain or limitation of movement in case of load, and no obvious differential diagnoses. Is an FHN clinically suspected, primarily radiographs of the pelvis ap and a Lauenstein projection of the hip involved should be carried out. When the radiographs are normal, an MRI of the hips should follow routinely. MRI allows the diagnosis of FNH with high accuracy. Furthermore, MRI reveals the site and the size of the necrotic area involved and evaluates the integrity of the joint surface and subchondral fractures. When ARCO stage II (ARCO: Association Research Circulation Osseous) is diagnosed and MRI does not allow one to determine the joint surface with certainty, a CT of the hip joints should be performed. The S3 guideline explains and recommends the use of the ARCO classification. Although, this classification of 1993 is still largely based on radiographs, the pragmatic use of an "extended" version seems reasonable. Today, classical radiographic criteria like impression of the joint surface and subchondral fractures ("crescent sign") are better to be evaluated by MRI, in cases of subtle findings MRI is even surpassed by CT. The extent of the necrosis in the femoral head as well as the size of the surface area involved is best revealed with MRI. Additionally, in the era of cross sectional imaging a stage "0" seems obsolete. The guideline also addresses practically important considerations about the differential diagnosis of misleading MRI findings. This especially holds true for bone marrow oedema in the femoral head which may be misinterpreted. The differentiating features between FHN, transient bone marrow oedema and destructive arthropathy are discussed. PMID- 26274558 TI - [Mid-Term Clinical Results after Open Rotator Cuff Reconstruction in Double-Row Technique with Titanium Anchor Screws]. AB - BACKGROUND: The double-row rotator cuff repair is discussed controversially. Despite improved biomechanical properties, reduced re-tear rates and higher costs, no significant difference compared to single-row fixation in the clinical results is found. Mid-term results of an open double-row fixation with titanium anchor screws are presented. MATERIAL AND METHODS: 237 patients (m = 142, f = 95, median age: 56.3 years) were operated in 2007 with this technique by the senior author (M. G.). Preoperatively, 2 years and 4,5 years postoperatively a subjective shoulder score (SSG) with follow-up rates of 86, 87 and 83 %, was evaluated. 5.1 years postoperatively an objective evaluation of 131 patients using the Constant-Murley scores (CS), the simple shoulder tests (SST), Gerber's shoulder value and the evaluation with school grades followed. The integrity of the cuff was checked with ultrasound. The absolute (re-tears and partial re tears) and the relative (re-tears, partial re-tears, thinning and thickening of the cuff) re-tear rates were evaluated. RESULTS: In SSG a highly significant improvement from 51 to 83 points was found (p < 0.001). In CS 80 points (min.: 18; max.: 100), and in SST 11 points (min.: 2; max.: 12) were achieved. The shoulder value of Gerber increased significantly from preoperative 28.1 to 84.5 % 5.1 years postoperative (p < 0.001).The absolute re-tear rate, evaluated in ultrasound was 7.6 %, the relative re-tear rate 17.6 %. For primary rotator cuff reconstructions a higher CS with 82 points and a lower relative re-tear rate with 10.5 % were found. The patient's age had no significant influence on the clinical outcome. The rupture size showed a significant impact on the re-tear rate and the scores (p < 0.05). Between the operated and healthy shoulder neither strength nor mobility were found to be significantly different. Men reached a highly significant better strength than women (p < 0.001) which also resulted in a significantly better outcome in the CS (p < 0.01). The costs for open titanium transfixation technique with 330 ? per case are markedly less than for arthroscopic suture bridge technique with 600 to 1000 ? per case. CONCLUSION: Open double-row cuff repair with titanium screws is a safe and cost effective technique with a low re-tear rate with comparable clinical results regarding open and arthroscopic procedures. PMID- 26274559 TI - [Bone Necrosis of the Hand]. AB - The bone necrosis of the hand is a common disease of the bone-cartilage complex. In principle, every bone of the hand can be affected. Compared to other osteonecroses of the hand the necrosis of the lunate occurs most frequently. Other diseases such as osteonecrosis of the Os scaphoideums (Morbus Preiser) are much rarer. Unfrequent diseases such as osteonecrosis of the metacarpal heads or all carpal bones are restricted to case descriptions. The lunate osteonecrosis leads to osteoarthritis of the wrist if untreated. A detailed clinical examination and adequate radiological diagnosis are essential. The lunate osteonecrosis is classified according to Lichtman and Ross based on radiographs. The treatment is being executed either conservatively or surgically, depending on the stage. In surgical treatment pressure relieving and revascularization procedures and rescue operations have been established. For all other osteonecroses of the hand no standardized therapy can be assigned because sufficient data are not available. Generally, the treatment for bone necroses of the hand should be found for each patient individually. PMID- 26274560 TI - Electron Channeling Contrast Imaging for Rapid III-V Heteroepitaxial Characterization. AB - Misfit dislocations in heteroepitaxial layers of GaP grown on Si(001) substrates are characterized through use of electron channeling contrast imaging (ECCI) in a scanning electron microscope (SEM). ECCI allows for imaging of defects and crystallographic features under specific diffraction conditions, similar to that possible via plan-view transmission electron microscopy (PV-TEM). A particular advantage of the ECCI technique is that it requires little to no sample preparation, and indeed can use large area, as-produced samples, making it a considerably higher throughput characterization method than TEM. Similar to TEM, different diffraction conditions can be obtained with ECCI by tilting and rotating the sample in the SEM. This capability enables the selective imaging of specific defects, such as misfit dislocations at the GaP/Si interface, with high contrast levels, which are determined by the standard invisibility criteria. An example application of this technique is described wherein ECCI imaging is used to determine the critical thickness for dislocation nucleation for GaP-on-Si by imaging a range of samples with various GaP epilayer thicknesses. Examples of ECCI micrographs of additional defect types, including threading dislocations and a stacking fault, are provided as demonstration of its broad, TEM-like applicability. Ultimately, the combination of TEM-like capabilities - high spatial resolution and richness of microstructural data - with the convenience and speed of SEM, position ECCI as a powerful tool for the rapid characterization of crystalline materials. PMID- 26274561 TI - Specific cancer-associated mutations in the switch III region of Ras increase tumorigenicity by nanocluster augmentation. AB - Hotspot mutations of Ras drive cell transformation and tumorigenesis. Less frequent mutations in Ras are poorly characterized for their oncogenic potential. Yet insight into their mechanism of action may point to novel opportunities to target Ras. Here, we show that several cancer-associated mutations in the switch III region moderately increase Ras activity in all isoforms. Mutants are biochemically inconspicuous, while their clustering into nanoscale signaling complexes on the plasma membrane, termed nanocluster, is augmented. Nanoclustering dictates downstream effector recruitment, MAPK-activity, and tumorigenic cell proliferation. Our results describe an unprecedented mechanism of signaling protein activation in cancer. PMID- 26274562 TI - Down-regulation of TORC2-Ypk1 signaling promotes MAPK-independent survival under hyperosmotic stress. AB - In eukaryotes, exposure to hypertonic conditions activates a MAPK (Hog1 in Saccharomyces cerevisiae and ortholog p38 in human cells). In yeast, intracellular glycerol accumulates to counterbalance the high external osmolarity. To prevent glycerol efflux, Hog1 action impedes the function of the aquaglyceroporin Fps1, in part, by displacing channel co-activators (Rgc1/2). However, Fps1 closes upon hyperosmotic shock even in hog1? cells, indicating another mechanism to prevent Fps1-mediated glycerol efflux. In our prior proteome wide screen, Fps1 was identified as a target of TORC2-dependent protein kinase Ypk1 (Muir et al., 2014). We show here that Fps1 is an authentic Ypk1 substrate and that the open channel state of Fps1 requires phosphorylation by Ypk1. Moreover, hyperosmotic conditions block TORC2-dependent Ypk1-mediated Fps1 phosphorylation, causing channel closure, glycerol accumulation, and enhanced survival under hyperosmotic stress. These events are all Hog1-independent. Our findings define the underlying molecular basis of a new mechanism for responding to hypertonic conditions. PMID- 26274563 TI - Reverse evolution leads to genotypic incompatibility despite functional and active site convergence. AB - Understanding the extent to which enzyme evolution is reversible can shed light on the fundamental relationship between protein sequence, structure, and function. Here, we perform an experimental test of evolutionary reversibility using directed evolution from a phosphotriesterase to an arylesterase, and back, and examine the underlying molecular basis. We find that wild-type phosphotriesterase function could be restored (>10(4)-fold activity increase), but via an alternative set of mutations. The enzyme active site converged towards its original state, indicating evolutionary constraints imposed by catalytic requirements. We reveal that extensive epistasis prevents reversions and necessitates fixation of new mutations, leading to a functionally identical sequence. Many amino acid exchanges between the new and original enzyme are not tolerated, implying sequence incompatibility. Therefore, the evolution was phenotypically reversible but genotypically irreversible. Our study illustrates that the enzyme's adaptive landscape is highly rugged, and different functional sequences may constitute separate fitness peaks. PMID- 26274564 TI - FAK/PYK2 promotes the Wnt/beta-catenin pathway and intestinal tumorigenesis by phosphorylating GSK3beta. AB - Aberrant activation of Wnt/beta-catenin signaling plays an unequivocal role in colorectal cancer, but identification of effective Wnt inhibitors for use in cancer remains a tremendous challenge. New insights into the regulation of this pathway could reveal new therapeutic point of intervention, therefore are greatly needed. Here we report a novel FAK/PYK2/GSK3beta(Y216)/beta-catenin regulation axis: FAK and PYK2, elevated in adenomas in APC(min/+) mice and in human colorectal cancer tissues, functioned redundantly to promote the Wnt/beta-catenin pathway by phosphorylating GSK3beta(Y216) to reinforce pathway output-beta catenin accumulation and intestinal tumorigenesis. We previously showed that Wnt induced beta-catenin accumulation requires Wnt-induced GSK3beta/beta-TrCP interaction; the current study revealed that phosphorylation of GSK3beta(Y216) was a molecular determinant of GSK3beta recruitment of beta-TrCP. Pharmacological inhibition of FAK/PYK2 suppressed adenoma formation in APC(min/+) mice accompanied with reduced intestinal levels of phospho-GSK3beta(Y216) and beta catenin, indicating that FAK/PYK2/GSK3beta(Y216) axis is critical for the activation of Wnt/beta-catenin signaling in APC driven intestinal tumorigenesis. PMID- 26274565 TI - Neuron-glia signaling in developing retina mediated by neurotransmitter spillover. AB - Neuron-glia interactions play a critical role in the maturation of neural circuits; however, little is known about the pathways that mediate their communication in the developing CNS. We investigated neuron-glia signaling in the developing retina, where we demonstrate that retinal waves reliably induce calcium transients in Muller glial cells (MCs). During cholinergic waves, MC calcium transients were blocked by muscarinic acetylcholine receptor antagonists, whereas during glutamatergic waves, MC calcium transients were inhibited by ionotropic glutamate receptor antagonists, indicating that the responsiveness of MCs changes to match the neurotransmitter used to support retinal waves. Using an optical glutamate sensor we show that the decline in MC calcium transients is caused by a reduction in the amount of glutamate reaching MCs. Together, these studies indicate that neurons and MCs exhibit correlated activity during a critical period of retinal maturation that is enabled by neurotransmitter spillover from retinal synapses. PMID- 26274566 TI - Using Polystyrene-block-poly(acrylic acid)-coated Metal Nanoparticles as Monomers for Their Homo- and Co-polymerization. AB - We present a template-free method for "polymerizing" nanoparticles into long chains without side branches. A variety of nanoparticles are encapsulated in polystyrene-block-poly(acrylic acid) (PSPAA) shells and then used as monomers for their self-assembly. Spherical PSPAA micelles upon acid treatment are known to assemble into cylindrical micelles. Exploiting this tendency, the core-shell nanoparticles are induced to aggregate, coalesce, and then transform into long chains. When more than one type of nanoparticles are used, random and block "copolymers" of nanoparticles can be obtained. Detailed procedures are reported for the PSPAA encapsulation of nanoparticles, homo- and co-polymerization of the core-shell nanoparticles, separation and purification of the resulting nanoparticle chains. Transformations of single-line chains into double- and triple-line chains are also presented. The synergy between the polymer shell and the embedded nanoparticles leads to an unusual chain-growth polymerization mode, giving long nanoparticle chains that are distinct from the products of the traditional step-growth aggregation process. PMID- 26274568 TI - Personality traits and body mass index: Modifiers and mechanisms. AB - OBJECTIVE: To identify how demographic factors (sex, age, ethnicity) modify the association between personality traits and body mass index (BMI) and to test the extent that diet and physical activity account for the personality-BMI relations. DESIGN: Cross-sectional study with a diverse sample (N = 5150, 50% female, 19% African American, 15% Hispanic). Participants completed a measure of the five major dimensions of personality and reported on their physical activity, diet and food intake behaviour, and height and weight. MAIN OUTCOME MEASURES: BMI and obesity (BMI >= 30). RESULTS: High Neuroticism was associated with higher BMI and risk for obesity, whereas Conscientiousness and, to a lesser extent, Extraversion and Openness were protective. These associations were generally stronger among women and older participants; there was less evidence for ethnicity as a moderator. Personality had similar relations with the behavioural factors, and physical activity, diet and regular meal rhythms accounted for approximately 50% of the association between Neuroticism and Conscientiousness and BMI. CONCLUSION: This study supports the links between personality traits and BMI and suggests that physical activity, more than diet, is a key factor in these associations. PMID- 26274567 TI - Physiology Lab Demonstration: Glomerular Filtration Rate in a Rat. AB - Measurements of glomerular filtration rate (GFR), and the fractional excretion of sodium (Na) and potassium (K) are critical in assessing renal function in health and disease. GFR is measured as the steady state renal clearance of inulin which is filtered at the glomerulus, but not secreted or reabsorbed along the nephron. The fractional excretion of Na and K can be determined from the concentration of Na and K in plasma and urine. The renal clearance of inulin can be demonstrated in an anesthetized animal which has catheters in the femoral artery, femoral vein and bladder. The equipment and supplies used for this procedure are those commonly available in a research core facility, and thus makes this procedure a practical means for measuring renal function. The purpose of this video is to demonstrate the procedures required to perform a lab demonstration in which renal function is assessed before and after a diuretic drug. The presented technique can be utilized to assess renal function in rat models of renal disease. PMID- 26274570 TI - Influence of avian leukosis virus long terminal repeat on biological activities of Marek's disease virus. AB - GX0101 was the first reported field strain of recombinant Marek's disease virus (MDV) that contained a long terminal repeat (LTR) from the reticuloendotheliosis virus (REV). It is a very virulent MDV strain, with relatively high horizontal transmission ability. The REV LTR in GX0101 genome was proved to decrease the pathogenicity but increase the potential for horizontal transmission of the virus. Here we constructed a recombinant MDV GX0101-ALV-LTR to study stability of avian leukosis virus (ALV) LTR at the REV LTR insertion site in GX0101 genome and its influence on biological activities of the recombinant virus. The results showed that GX0101-ALV-LTR was able to replicate stably both in vitro and in vivo. ALV LTR remained stable in chickens infected either by inoculation with the recombinant virus GX0101-ALV-LTR or by horizontal transmission, as well as in cell culture. The pathogenic properties of GX0101-ALV-LTR virus were evaluated in infected specific-pathogen-free chickens. The present study demonstrated that the GX0101-ALV-LTR virus had a weaker inhibitory effect on the growth rates of the infected chickens and induced weaker immunosuppressive effects. Horizontal transmission ability of the GX0101-ALV-LTR virus appeared to be similar with its parental virus GX0101. In short, ALV LTR was stable in GX0101 after replacing REV LTR, and the recombinant virus showed similar horizontal transmission ability but decreased pathogenicity. PMID- 26274569 TI - Susceptibility of wild passerines to subtype H5N1 highly pathogenic avian influenza viruses. AB - Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype have spread throughout many areas of Asia, Europe and Africa, and numerous cases of HPAI outbreaks in domestic and wild birds have been reported. Although recent studies suggest that the dissemination of H5N1 viruses is closely linked to the migration of wild birds, information on the potential for viral infection in species other than poultry and waterfowl is relatively limited. To investigate the susceptibility of terrestrial wild birds to infection with H5N1 HPAI viruses, common reed buntings (Emberiza schoeniclus), pale thrushes (Turdus pallidus) and brown-eared bulbuls (Hypsipetes amaurotis) were infected with A/mountain hawk eagle/Kumamoto/1/07(H5N1) and A/whooper swan/Aomori/1/08(H5N1). The results showed that common reed buntings and brown-eared bulbuls were severely affected by both virus strains (100% mortality). While pale thrushes did not exhibit any clinical signs, seroconversion was confirmed. In common reed buntings, intraspecies-transmission of A/whooper swan/Aomori/1/08 to contact birds was also confirmed. The findings show that three passerine species; common reed buntings, brown-eared bulbuls and pale thrushes are susceptible to infection by H5N1 HPAI viruses, which emphasizes that continued surveillance of species other than waterfowl is crucial for effective monitoring of H5N1 HPAI virus outbreaks. PMID- 26274574 TI - Large Area Directed Self-Assembly of Sub-10 nm Particles with Single Particle Positioning Resolution. AB - Directed self-assembly of nanoparticles (DSA-n) holds great potential for device miniaturization in providing patterning resolution and throughput that exceed existing lithographic capabilities. Although nanoparticles excel at assembling into regular close-packed arrays, actual devices on the other hand are often laid out in sparse and complex configurations. Hence, the deterministic positioning of single or few particles at specific positions with low defect density is imperative. Here, we report an approach of DSA-n that satisfies these requirements with less than 1% defect density over micrometer-scale areas and at technologically relevant sub-10 nm dimensions. This technique involves a simple and robust process where a solvent film containing sub-10 nm gold nanoparticles climbs against gravity to coat a prepatterned template. Particles are placed individually into nanoscale cavities, or between nanoposts arranged in varying degrees of geometric complexity. Brownian dynamics simulations suggest a mechanism in which the particles are pushed into the template by a nanomeniscus at the drying front. This process enables particle-based self-assembly to access the sub-10 nm dimension, and for device fabrication to benefit from the wealth of chemically synthesized nanoparticles with unique material properties. PMID- 26274575 TI - Heck Reactions Catalyzed by Ultrasmall and Uniform Pd Nanoparticles Supported on Polyaniline. AB - Using air as the oxidant instead of the traditionally employed persulfates, the smaller and more uniform Pd nanoparticles (around 2 nm) supported on polyaniline (Pd@PANI) can be easily fabricated by the oxidation-polymerization of aniline with PdCl2. This material is an efficient and environmentally friendly catalyst for Heck reactions due to its recyclability, low loading, and ligand-free and mild reaction conditions. It was even tolerant to sulfur-containing substrates. This work reports the Pd@PANI-catalyzed Heck reactions with very wide substrate scopes, and discloses the catalytic mechanisms based on experimental findings and results of catalyst analysis and characterization. PMID- 26274576 TI - Biofouling-resilient nanoporous gold electrodes for DNA sensing. AB - Electrochemical nucleic acid sensors are promising tools for point-of-care diagnostic platforms with their facile integration with electronics and scalability. However, nucleic acid detection in complex biological fluids is challenging as biomolecules nonspecifically adsorb on the electrode surface and adversely affect the sensor performance by obscuring the transport of analytes and redox species to the electrode. We report that nanoporous gold (np-Au) electrodes, prepared by a microfabrication-compatible self-assembly process and functionalized with DNA probes, enabled detection of target DNA molecules (10-200 nM) in physiologically relevant complex media (bovine serum albumin and fetal bovine serum). In contrast, the sensor performance was compromised for planar gold electrodes in the same conditions. Hybridization efficiency decreased by 10% for np-Au with coarser pores revealing a pore-size dependence of sensor performance in biofouling conditions. This nanostructure-dependent functionality in complex media suggests that the pores with the optimal size and geometry act as sieves for blocking the biomolecules from inhibiting the surfaces within the porous volume while allowing the transport of nucleic acid analytes and redox molecules. PMID- 26274577 TI - Prediction and Synthesis of Strain Tolerant RbCuTe Crystals Based on Rotation of One-Dimensional Nano Ribbons within a Three-Dimensional Inorganic Network. AB - A unique possibility for a simple strain tolerant inorganic solid is envisioned whereby a set of isolated, one-dimensional (1D) nano objects are embedded in an elastically soft three-dimensional (3D) atomic matrix thus forming an interdimensional hybrid structure (IDHS). We predict theoretically that the concerted rotation of 1D nano objects could allow such IDHSs to tolerate large strain values with impunity. Searching theoretically among the 1:1:1 ABX compounds of I-I-VI composition, we identified, via first-principles thermodynamic theory, RbCuTe, which is a previously unreported but now predicted to-be-stable compound in the MgSrSi-type structure, in space group Pnma. The predicted structure of RbCuTe consists of ribbons of copper and telluride atoms placed antipolar to one another throughout the lattice with rubidium atoms acting as a matrix. A novel synthetic adaptation utilizing liquid rubidium and vacuum annealing of the mixed elemental reagents in fused silica tubes as well as in situ (performed at the Advanced Photon Source) and ex situ structure determination confirmed the stability and predicted structure of RbCuTe. First principles calculations then showed that the application of up to ~30% uniaxial strain on the ground-state structure result in a buildup of internal stress not exceeding 0.5 GPa. The increase in total energy is 15-fold smaller than what is obtained for the same RbCuTe material but in structures having a contiguous set of 3D chemical bonds spanning the entire crystal. Furthermore, electronic structure calculations revealed that the HOMO is a 1D energy band localized on the CuTe ribbons and that the 1D insulating band structure is also resilient to such large strains. This combined theory and experiment study reveals a new type of strain tolerant inorganic material. PMID- 26274578 TI - Phosphine Gas Adsorption in a Series of Metal-Organic Frameworks. AB - For the first time, phosphine adsorption has been evaluated in a series of metal organic frameworks (MOFs). Open-metal coordination sites were found to significantly enhance the ability of MOFs to adsorb highly toxic phosphine gas, with the identity of the open-metal site also modulating the amount of gas adsorbed. The MOFs studied outperform activated carbon, a commonly used material to capture phosphine. PMID- 26274579 TI - Associations to pain and analgesics in Indian pain patients and health workers. AB - AIM: This study explores the attitudes toward analgesic therapy among persistent pain patients and health workers in palliative care in India. METHODS: Free word association was used and quantitative content analysis was performed. RESULTS: A total of 59 patients and 28 health workers participated. In total, 41% of the patients had <5/10 points on a pain scale. A total of 3733 associations were recovered. Personal associations were majorly coming from patients having negative connotation. Morphine produced few associations, especially among patients. Most of them were about pain relief and for patients about negative emotions. CONCLUSION: Two types of knowledge were detectable, differing in quality and quantity. One was based on lived experience among patients; the other arose from scientific foundation among health workers. PMID- 26274580 TI - Remembrances of Hannelore Wass. AB - A brief tribute to a dear friend and former colleague, Hannelore Wass, these remembrances evidence her delightfully humorous and mischievous side as well as celebrate her long and illustrious career. A woman in full, she is sorely missed but fondly remembered. PMID- 26274581 TI - Dielectric Investigation of Parylene D Thin Films: Relaxation and Conduction Mechanisms. AB - Parylene is a generic name indicating a family of polymers with the basic chemical structure of poly-p-xylylene. Parylene N and Parylene C are the most popular for applications. Curiously, Parylene D (poly( dichloro-p-xylylene), (C8H6Cl2)) was forgotten for applications. This report is the consequence of a later availability of a commercial dimer of Parylene D and also to the recent advent of fluorinated Parylenes allowing extending applications at higher temperatures. In our work, from a dielectric analysis, we present the potentialities of Parylene D for applications particularly interesting for integration in organic field-effect transistors. Dielectric and electrical properties, macromolecular structures, and dynamics interaction with electric field as a function of frequency and temperature are studied in 5.8 MUm thick Parylene D grown by chemical vapor deposition. More exactly, the dielectric permittivity, the dissipation factor, the electrical conductivity, and the electric modulus of Parylene D were investigated in a wide temperature and frequency ranges from -140 to +350 degrees C and from 0.1 Hz to 1 MHz, respectively. According to the temperature dependence of the dielectric permittivity, Parylene D has two different dielectric responses. It is retained as a nonpolar material at very low temperature (like Parylene N) and as a polar material at high temperature (like parylene C). The dissipation factor shows the manifestation of two relaxations mechanisms: gamma and beta at very low and high temperatures, respectively. The gamma relaxation is assigned to the local motions of the C-H end of the chains when the cryogenic temperature range is approached. A broad peak in tan delta is assigned to the beta relaxation. It corresponds to rotational motion of some polar C-Cl groups. For temperature above 260 degrees C a mechanism of Maxwell-Wagner-Sillars polarization at the amorphous/crystalline interfaces was identified with two activation energies of Ea1 = 2.12 eV and Ea2 = 3.8 eV. Moreover, the conductivity and the dielectric permittivity relaxation processes have been discussed in terms of nearly constant loss (NCL) and universal dynamic regime (UDR). Finally, ionic conduction and electrode polarization effects are identified at very high temperatures and their physical origins are discussed. PMID- 26274582 TI - Assessing the Risk of Invasion by Tephritid Fruit Flies: Intraspecific Divergence Matters. AB - Widely distributed species often show strong phylogeographic structure, with lineages potentially adapted to different biotic and abiotic conditions. The success of an invasion process may thus depend on the intraspecific identity of the introduced propagules. However, pest risk analyses are usually performed without accounting for intraspecific diversity. In this study, we developed bioclimatic models using MaxEnt and boosted regression trees approaches, to predict the potential distribution in Europe of six economically important Tephritid pests (Ceratitis fasciventris (Bezzi), Bactrocera oleae (Rossi), Anastrepha obliqua (Macquart), Anastrepha fraterculus (Wiedemann), Rhagoletis pomonella (Walsh) and Bactrocera cucurbitae (Coquillet)). We considered intraspecific diversity in our risk analyses by independently modeling the distributions of conspecific lineages. The six species displayed different potential distributions in Europe. A strong signal of intraspecific climate envelope divergence was observed in most species. In some cases, conspecific lineages differed strongly in potential distributions suggesting that taxonomic resolution should be accounted for in pest risk analyses. No models (lineage- and species-based approaches) predicted high climatic suitability in the entire invaded range of B. oleae-the only species whose intraspecific identity of invading populations has been elucidated-in California. Host availability appears to play the most important role in shaping the geographic range of this specialist pest. However, climatic suitability values predicted by species-based models are correlated with population densities of B. oleae globally reported in California. Our study highlights how classical taxonomic boundaries may lead to under- or overestimation of the potential pest distributions and encourages accounting for intraspecific diversity when assessing the risk of biological invasion. PMID- 26274583 TI - Effects of Degree and Timing of Social Housing on Reversal Learning and Response to Novel Objects in Dairy Calves. AB - Rodents and primates deprived of early social contact exhibit deficits in learning and behavioural flexibility. They often also exhibit apparent signs of elevated anxiety, although the relationship between these effects has not been studied. To investigate whether dairy calves are similarly affected, we first compared calves housed in standard individual pens (n = 7) to those housed in a dynamic group with access to their mothers (n = 8). All calves learned to approach the correct stimulus in a visual discrimination task. Only one individually housed calf was able to re-learn the task when the stimuli were reversed, compared to all but one calf from the group. A second experiment investigated whether this effect might be explained by anxiety in individually housed animals interfering with their learning, and tested varying degrees of social contact in addition to the complex group: pair housing beginning early (approximately 6 days old) and late (6 weeks old). Again, fewer individually reared calves learned the reversal task (2 of 10 or 20%) compared to early paired and grouped calves (16 of 21 or 76% of calves). Late paired calves had intermediate success. Individually housed calves were slower to touch novel objects, but the magnitude of the fear response did not correlate with reversal performance. We conclude that individually housed calves have learning deficits, but these deficits were not likely associated with increased anxiety. PMID- 26274584 TI - A Systematic Review of Mortality from Untreated Scrub Typhus (Orientia tsutsugamushi). AB - BACKGROUND: Scrub typhus, a bacterial infection caused by Orientia tsutsugamushi, is increasingly recognized as an important cause of fever in Asia, with an estimated one million infections occurring each year. Limited access to health care and the disease's non-specific symptoms mean that many patients are undiagnosed and untreated, but the mortality from untreated scrub typhus is unknown. This review systematically summarizes the literature on the untreated mortality from scrub typhus and disease outcomes. METHODOLOGY/PRINCIPAL FINDINGS: A literature search was performed to identify patient series containing untreated patients. Patients were included if they were symptomatic and had a clinical or laboratory diagnosis of scrub typhus and excluded if they were treated with antibiotics. The primary outcome was mortality from untreated scrub typhus and secondary outcomes were total days of fever, clinical symptoms, and laboratory results. A total of 76 studies containing 89 patient series and 19,644 patients were included in the final analysis. The median mortality of all patient series was 6.0% with a wide range (min-max) of 0-70%. Many studies used clinical diagnosis alone and had incomplete data on secondary outcomes. Mortality varied by location and increased with age and in patients with myocarditis, delirium, pneumonitis, or signs of hemorrhage, but not according to sex or the presence of an eschar or meningitis. Duration of fever was shown to be long (median 14.4 days Range (9-19)). CONCLUSIONS: Results show that the untreated mortality from scrub typhus appears lower than previously reported estimates. More data are required to clarify mortality according to location and host factors, clinical syndromes including myocarditis and central nervous system disease, and in vulnerable mother-child populations. Increased surveillance and improved access to diagnostic tests are required to accurately estimate the untreated mortality of scrub typhus. This information would facilitate reliable quantification of DALYs and guide empirical treatment strategies. PMID- 26274586 TI - Reliability of the Actigraph GT3X+ Accelerometer in Adults under Free-Living Conditions. AB - BACKGROUND: Reliability of the Actigraph GT3X+ accelerometer has not been determined under normal wear time criteria in a large sample of subjects and accelerometer units. The aim of this study was to assess contralateral hip difference and inter-instrument reliability of the Actigraph GT3X+ monitor in adults under long-term free-living conditions. METHODS: Eighty-seven adult subjects (28 men; mean (standard deviation) age 31.3 (12.2) years; body mass index 23.7 (3.1) kg/m2) concurrently wore two GT3X+ accelerometers (174 units in total) attached to contralateral hips for 21 days. Reliability was assessed using Bland-Altman plots, mixed model regression analyses and absolute measures of agreement for different lengths of data accumulation (single-day-, 7-day- and 21 day periods). RESULTS: There were no significant differences between contralateral hips (effect size <=0.042; p >=.213). Inter-instrument reliability increased with increased length of data-accumulation. For a 7-day measurement period (n = 232 weeks), limits of agreement were +/-68 cpm (vertical axis) and +/ 81.3 cpm (vector magnitude) for overall physical activity (PA) level, +/-51 min for sedentary time, +/-18.2 min for light PA, +/-6.3 min for moderate PA, +/-3.5 min for vigorous PA, and +/-6.7 min for moderate-to-vigorous PA. CONCLUSIONS: The Actigraph GT3X+ accelerometer is a reliable tool for measuring PA in adults under free-living conditions using normal data-reduction criteria. Contralateral hip differences are very small. We suggest accelerometers be attached to the right hip and data to be accumulated over several days of measurement. PMID- 26274585 TI - Adherence to the 2012 American College of Rheumatology (ACR) Guidelines for Management of Gout: A Survey of Brazilian Rheumatologists. AB - OBJECTIVE: To describe the current pharmacological approach to gout treatment reported by rheumatologists in Brazil. METHODS: We performed a cross-sectional survey study using an online questionnaire e-mailed to 395 rheumatologists, randomly selected, from among the members of the Brazilian Society of Rheumatology. RESULTS: Three hundred and nine rheumatologists (78.2%) responded to the survey. For acute gout attacks, combination therapy (NSAIDs or steroid + colchicine) was often used, even in monoarticular involvement, and colchicine was commonly started as monotherapy after 36 hours or more from onset of attack. During an acute attack, urate-lowering therapy (ULT) was withdrawn by approximately a third of rheumatologists. Anti-inflammatory prophylaxis (98% colchicine) was initiated when ULT was started in most cases (92.4%), but its duration was varied. Most (70%) respondents considered the target serum uric acid level to be less than 6 mg/dl. Approximately 50% of rheumatologists reported starting allopurinol at doses of 100 mg daily or less and 42% reported the initial dose to be 300 mg daily in patients with normal renal function. ULT was maintained indefinitely in 76% of gout patients with tophi whereas in gout patients without tophi its use was kept indefinitely in 39.6%. CONCLUSION: This is the first study evaluating gout treatment in a representative, random sample of Brazilian rheumatologists describing common treatment practices among these specialists. We identified several gaps in reported gout management, mainly concerning the use of colchicine and ULT and the duration of anti-inflammatory prophylaxis and ULT. Since rheumatologists are considered as opinion leaders in this disease, a program for improving quality of care for gout patients should focus on increasing their knowledge in this common disease. PMID- 26274588 TI - Invited Commentary: Role of US Contrast Agents in the Assessment of Indeterminate Solid and Cystic Lesions in Native and Transplant Kidneys. PMID- 26274587 TI - Production of Uniform 3D Microtumors in Hydrogel Microwell Arrays for Measurement of Viability, Morphology, and Signaling Pathway Activation. AB - Despite significant investments in cancer research and drug discovery/development, the rate of new cancer drug approval is <=5% and most cases of metastatic cancer remain incurable. Ninety-five percent of new cancer drugs fail in clinical development because of a lack of therapeutic efficacy and/or unacceptable toxicity. One of the major factors responsible for the low success rate of anticancer drug development is the failure of preclinical models to adequately recapitulate the complexity and heterogeneity of human cancer. For throughput and capacity reasons, high-throughput screening growth inhibition assays almost exclusively use two-dimensional (2D) monolayers of tumor cell lines cultured on tissue culture-treated plastic/glass surfaces in serum-containing medium. However, these 2D tumor cell line cultures fail to recapitulate the three dimensional (3D) context of cells in solid tumors even though the tumor microenvironment has been shown to have a profound effect on anticancer drug responses. Tumor spheroids remain the best characterized and most widely used 3D models; however, spheroid sizes tend to be nonuniform, making them unsuitable for high-throughput drug testing. To circumvent this challenge, we have developed defined size microwell arrays using nonadhesive hydrogels that are applicable to a wide variety of cancer cell lines to fabricate size-controlled 3D microtumors. We demonstrate that the hydrogel microwell array platform can be applied successfully to generate hundreds of uniform microtumors within 3-6 days from many cervical and breast, as well as head and neck squamous cell carcinoma (HNSCC) cells. Moreover, controlling size of the microwells in the hydrogel array allows precise control over the size of the microtumors. Finally, we demonstrate the application of this platform technology to probe activation as well as inhibition of epidermal growth factor receptor (EGFR) signaling in 3D HNSCC microtumors in response to EGF and cetuximab treatments, respectively. We believe that the ability to generate large numbers of HNSCC microtumors of uniform size and 3D morphology using hydrogel arrays will provide more physiological in vitro 3D tumor models to investigate how tumor size influences signaling pathway activation and cancer drug efficacy. PMID- 26274589 TI - Lectin-Based Characterization of Vascular Cell Microparticle Glycocalyx. AB - Microparticles (MPs) are released constitutively and from activated cells. MPs play significant roles in vascular homeostasis, injury, and as biomarkers. The unique glycocalyx on the membrane of cells has frequently been exploited to identify specific cell types, however the glycocalyx of the MPs has yet to be defined. Thus, we sought to determine whether MPs, released both constitutively and during injury, from vascular cells have a glycocalyx matching those of the parental cell type to provide information on MP origin. For these studies we used rat pulmonary microvascular and artery endothelium, pulmonary smooth muscle, and aortic endothelial cells. MPs were collected from healthy or cigarette smoke injured cells and analyzed with a panel of lectins for specific glycocalyx linkages. Intriguingly, we determined that the MPs released either constitutively or stimulated by CSE injury did not express the same glycocalyx of the parent cells. Further, the glycocalyx was not unique to any of the specific cell types studied. These data suggest that MPs from both normal and healthy vascular cells do not share the parental cell glycocalyx makeup. PMID- 26274591 TI - In Silico Identification of Protein S-Palmitoylation Sites and Their Involvement in Human Inherited Disease. AB - S-Palmitoylation is a key regulatory mechanism controlling protein targeting, localization, stability, and activity. Since increasing evidence shows that its disruption is implicated in many human diseases, the identification of palmitoylation sites is attracting more attention. However, the computational methods that are published so far for this purpose have suffered from a poor balance of sensitivity and specificity; hence, it is difficult to get a good generalized prediction ability on an external validation set, which holds back the further analysis of associations between disruption of palmitoylation and human inherited diseases. In this work, we present a reliable identification method for protein S-palmitoylation sites, called SeqPalm, based on a series of newly composed features from protein sequences and the synthetic minority oversampling technique. With only 16 extracted key features, this approach achieves the most favorable prediction performance up to now with sensitivity, specificity, and Matthew's correlation coefficient values of 95.4%, 96.3%, and 0.917, respectively. Then, all known disease-associated variations are studied by SeqPalm. It is found that 243 potential loss or gain of palmitoylation sites are highly associated with human inherited disease. The analysis presents several potential therapeutic targets for inherited diseases associated with loss or gain of palmitoylation function. There are even biological evidence that are coordinate with our prediction results. Therefore, this work presents a novel approach to discover the molecular basis of pathogenesis associated with abnormal palmitoylation. SeqPalm is now available online at http://lishuyan.lzu.edu.cn/seqpalm , which can not only annotate the palmitoylation sites of proteins but also distinguish loss or gain of palmitoylation sites by protein variations. PMID- 26274592 TI - Attending to the bodily self. AB - Humphreys and Sui provide a powerful theoretical framework to explain processing biases toward self-related information. However, the framework is primarily applied to information relevant to a conceptual self-representation. Here, we show a similar processing bias for information related to the bodily self, grounded in sensorimotor representations. Furthermore, we can use bodily illusions to explore the ways in which embodied self-associations can affect our perceptual and attentional processing. It is possible to extend the current framework to take into account these effects, and we argue that this will yield considerable benefits for our understanding of self-relevance. PMID- 26274590 TI - Permeation of Therapeutic Drugs in Different Formulations across the Airway Epithelium In Vitro. AB - BACKGROUND: Pulmonary drug delivery is characterized by short onset times of the effects and an increased therapeutic ratio compared to oral drug delivery. This delivery route can be used for local as well as for systemic absorption applying drugs as single substance or as a fixed dose combination. Drugs can be delivered as nebulized aerosols or as dry powders. A screening system able to mimic delivery by the different devices might help to assess the drug effect in the different formulations and to identify potential interference between drugs in fixed dose combinations. The present study evaluates manual devices used in animal studies for their suitability for cellular studies. METHODS: Calu-3 cells were cultured submersed and in air-liquid interface culture and characterized regarding mucus production and transepithelial electrical resistance. The influence of pore size and material of the transwell membranes and of the duration of air-liquid interface culture was assessed. Compounds were applied in solution and as aerosols generated by MicroSprayer IA-1C Aerosolizer or by DP-4 Dry Powder Insufflator using fluorescein and rhodamine 123 as model compounds. Budesonide and formoterol, singly and in combination, served as examples for drugs relevant in pulmonary delivery. RESULTS AND CONCLUSIONS: Membrane material and duration of air-liquid interface culture had no marked effect on mucus production and tightness of the cell monolayer. Co-application of budesonide and formoterol, applied in solution or as aerosol, increased permeation of formoterol across cells in air-liquid interface culture. Problems with the DP-4 Dry Powder Insufflator included compound-specific delivery rates and influence on the tightness of the cell monolayer. These problems were not encountered with the MicroSprayer IA-1C Aerosolizer. The combination of Calu-3 cells and manual aerosol generation devices appears suitable to identify interactions of drugs in fixed drug combination products on permeation. PMID- 26274593 TI - Human papillomavirus status, anal cytology and histopathological outcome in HIV positive patients. AB - BACKGROUND: Human papillomavirus (HPV) are responsible for a broad spectrum of mucocutaneous infections and may cause squamous cell carcinoma following long standing infection . Oncogenic HPV, most commonly HPV 16, are detectable in over 90% of cervical intraepithelial neoplasia and anal intraepithelial neoplasia (AIN). Human immunodeficiency virus (HIV) infection is strongly associated with a higher prevalence of chronic HPV infection, a higher incidence of AIN and an increased risk for anal cancer (AC). In September 2013, guidelines concerning prevention, screening and treatment of AIN for patients affected by HIV were issued by the German AIDS society. OBJECTIVE: In order to validate the suggested screening procedure, we analysed data from 123 male and female patients with HIV infection that regularly present in our outpatient clinic. METHODS: Anal cytology, HPV typing and high-resolution anoscopy (HRA) were performed. RESULTS: Our results show that screening by anal cytology only identifies a minority of patients with high grade AIN (AIN 3) histology. Patients with normal cytology (NILM, cytology graded negative for intraepithelial lesion or malignancy; n = 5, 29.4%), atypical squamous cells of undetermined significance (ASCUS; n = 5, 71.4%) and low grade squamous intraepithelial lesion (LSIL; n = 8, 44.5%) showed highly dysplastic lesions (AIN 2 and 3) in the histological workup more frequently than expected. Additionally, high-grade squamous intraepithelial lesion (HSIL) was strongly associated with detection of high-risk oncogenic HPV. CONCLUSION: Anal cytology as the solitary screening tool for anal cancer fails to detect anal dysplasia in a considerable number of patients. Additionally, HPV typing and possibly further biomarkers might be applied to identify those patients with a higher risk of developing anal carcinoma, in order to monitor them more closely or directly transfer them to HRA. PMID- 26274594 TI - What is your diagnosis? Unusual cells in the blood smear from a dog. PMID- 26274599 TI - Biosensors for Cell Analysis. AB - Biosensors first appeared several decades ago to address the need for monitoring physiological parameters such as oxygen or glucose in biological fluids such as blood. More recently, a new wave of biosensors has emerged in order to provide more nuanced and granular information about the composition and function of living cells. Such biosensors exist at the confluence of technology and medicine and often strive to connect cell phenotype or function to physiological or pathophysiological processes. Our review aims to describe some of the key technological aspects of biosensors being developed for cell analysis. The technological aspects covered in our review include biorecognition elements used for biosensor construction, methods for integrating cells with biosensors, approaches to single-cell analysis, and the use of nanostructured biosensors for cell analysis. Our hope is that the spectrum of possibilities for cell analysis described in this review may pique the interest of biomedical scientists and engineers and may spur new collaborations in the area of using biosensors for cell analysis. PMID- 26274601 TI - Modeling Signaling Networks to Advance New Cancer Therapies. AB - Cell signaling pathways control cells' responses to their environment through an intricate network of proteins and small molecules partitioned by intracellular structures, such as the cytoskeleton and nucleus. Our understanding of these pathways has been revised recently with the advent of more advanced experimental techniques; no longer are signaling pathways viewed as linear cascades of information flowing from membrane-bound receptors to the nucleus. Instead, such pathways must be understood in the context of networks, and studying such networks requires an integration of computational and experimental approaches. This understanding is becoming more important in designing novel therapies for diseases such as cancer. Using the MAPK (mitogen-activated protein kinase) and PI3K (class I phosphoinositide-3' kinase) pathways as case studies of cellular signaling, we give an overview of these pathways and their functions. We then describe, using a number of case studies, how computational modeling has aided in understanding these pathways' deregulation in cancer, and how such understanding can be used to optimally tailor current therapies or help design new therapies against cancer. PMID- 26274600 TI - Advances in Antibody Design. AB - The use of monoclonal antibodies as therapeutics requires optimizing several of their key attributes. These include binding affinity and specificity, folding stability, solubility, pharmacokinetics, effector functions, and compatibility with the attachment of additional antibody domains (bispecific antibodies) and cytotoxic drugs (antibody-drug conjugates). Addressing these and other challenges requires the use of systematic design methods that complement powerful immunization and in vitro screening methods. We review advances in designing the binding loops, scaffolds, domain interfaces, constant regions, post-translational and chemical modifications, and bispecific architectures of antibodies and fragments thereof to improve their bioactivity. We also highlight unmet challenges in antibody design that must be overcome to generate potent antibody therapeutics. PMID- 26274603 TI - Drug therapies for metastatic castration-resistant prostate cancer. AB - Management of metastatic castration-resistant prostate cancer has changed markedly over the last decade with major shifts in the treatment paradigm, although ultimately still will progress despite currently available therapies. The sequencing or combination of these agents is an area of active investigation, since definitive prospective randomized trials to define the optimal choice of drug sequence have yet to be done or resulted. This article will highlight pivotal trials for currently approved therapies for metastatic castration resistant prostate cancer and a suggestion for sequencing of these agents, as well as highlighting investigations using novel therapies for advanced prostate cancer. PMID- 26274602 TI - Hypoxia and Temperature Regulated Morphogenesis in Candida albicans. AB - Candida albicans is a common commensal in the human gut but in predisposed patients it can become an important human fungal pathogen. As a commensal, C. albicans adapts to low-oxygen conditions and represses its hyphal development by the transcription factor Efg1, which under normoxia activates filamentation. The repressive hypoxic but not the normoxic function of Efg1 required its unmodified N-terminus, was prevented by phosphomimetic residues at normoxic phosphorylation sites T179 and T206 and occurred only at temperatures <=35 degrees C. Genome-wide binding sites for native Efg1 identified 300 hypoxia-specific target genes, which overlapped partially with hypoxic binding sites for Ace2, a known positive regulator of hypoxic filamentation. Transcriptional analyses revealed that EFG1, ACE2 and their identified targets BCR1 and BRG1 encode an interconnected regulatory hub, in which Efg1/Bcr1 act as negative and Ace2/Brg1 act as positive regulators of gene expression under hypoxia. In this circuit, the hypoxic function of Ace2 was stimulated by elevated CO2 levels. The hyperfilamentous phenotype of efg1 and bcr1 mutants depended on Ace2/Brg1 regulators and required increased expression of genes encoding Cek1 MAP kinase and its downstream target Cph1. The intricate temperature-dependent regulatory mechanisms under hypoxia suggest that C. albicans restricts hyphal morphogenesis in oxygen-poor body niches, possibly to persist as a commensal in the human host. PMID- 26274604 TI - Correction to Levels of Polycyclic Aromatic Hydrocarbons in Maternal Serum and Risk of Neural Tube Defects in Offspring. PMID- 26274606 TI - Non-Selective Evolution of Growing Populations. AB - Non-selective effects, like genetic drift, are an important factor in modern conceptions of evolution, and have been extensively studied for constant population sizes (Kimura, 1955; Otto and Whitlock, 1997). Here, we consider non selective evolution in the case of growing populations that are of small size and have varying trait compositions (e.g. after a population bottleneck). We find that, in these conditions, populations never fixate to a trait, but tend to a random limit composition, and that the distribution of compositions "freezes" to a steady state. This final state is crucially influenced by the initial conditions. We obtain these findings from a combined theoretical and experimental approach, using multiple mixed subpopulations of two Pseudomonas putida strains in non-selective growth conditions (Matthijs et al, 2009) as model system. The experimental results for the population dynamics match the theoretical predictions based on the Polya urn model (Eggenberger and Polya, 1923) for all analyzed parameter regimes. In summary, we show that exponential growth stops genetic drift. This result contrasts with previous theoretical analyses of non selective evolution (e.g. genetic drift), which investigated how traits spread and eventually take over populations (fixate) (Kimura, 1955; Otto and Whitlock, 1997). Moreover, our work highlights how deeply growth influences non-selective evolution, and how it plays a key role in maintaining genetic variability. Consequently, it is of particular importance in life-cycles models (Melbinger et al, 2010; Cremer et al, 2011; Cremer et al, 2012) of periodically shrinking and expanding populations. PMID- 26274605 TI - Photolysis of Low-Brominated Diphenyl Ethers and Their Reactive Oxygen Species Related Reaction Mechanisms in an Aqueous System. AB - To date, no report was concerned with participation of reactive oxygen species in waters during photolysis of low-brominated diphenyl ethers (LBDEs). Herein, we found that electron spin resonance (ESR) signals rapidly increased with increasing irradiation time in the solution of LBDEs and 4-oxo-TMP solutions. But this phenomenon did not occur in the presence of NaN3 (1O2 quencher) demonstrating generation of 1O2 in process of LBDEs photolysis. The indirect photolytic contribution rate for BDE-47 and BDE-28 was 18.8% and 17.3% via 1O2, and 4.9% and 6.6% via .OH, respectively. Both D2O and NaN3 experiments proved that the indirect photolysis of LBDEs was primarily attributable to 1O2. The bimolecular reaction rate constants of 1O2 with BDE-47 and BDE-28 were 3.12 and 3.64 * 106 M-1 s-1, respectively. The rate constants for BDE-47 and BDE-28 (9.01 and 17.52 * 10-3 min-1), added to isopropyl alcohol, were very close to those (9.65 and 18.42 * 10-3 min-1) in water, proving the less indirect photolytic contribution of .OH in water. This is the first comprehensive investigation examining the indirect photolysis of LBDEs in aqueous solution. PMID- 26274608 TI - Variants of Phosphotriesterase for the Enhanced Detoxification of the Chemical Warfare Agent VR. AB - The V-type organophosphorus nerve agents are among the most hazardous compounds known. Previous efforts to evolve the bacterial enzyme phosphotriesterase (PTE) for the hydrolytic decontamination of VX resulted in the identification of the variant L7ep-3a, which has a kcat value more than 2 orders of magnitude higher than that of wild-type PTE for the hydrolysis of VX. Because of the relatively small size of the O-ethyl, methylphosphonate center in VX, stereoselectivity is not a major concern. However, the Russian V-agent, VR, contains a larger O isobutyl, methylphosphonate center, making stereoselectivity a significant issue since the SP-enantiomer is expected to be significantly more toxic than the RP enantiomer. The three-dimensional structure of the L7ep-3a variant was determined to a resolution of 2.01 A (PDB id: 4ZST ). The active site of the L7ep-3a mutant has revealed a network of hydrogen bonding interactions between Asp-301, Tyr-257, Gln-254, and the hydroxide that bridges the two metal ions. A series of new analogues that mimic VX and VR has helped to identify critical structural features for the development of new enzyme variants that are further enhanced for the catalytic detoxification of VR and VX. The best of these mutants has been shown to have a reversed stereochemical preference for the hydrolysis of VR chiral center analogues. This mutant hydrolyzes the two enantiomers of VR 160- and 600-fold faster than wild-type PTE hydrolyzes the SP-enantiomer of VR. PMID- 26274607 TI - Residential Radon Exposure and Skin Cancer Incidence in a Prospective Danish Cohort. AB - BACKGROUND: Although exposure to UV radiation is the major risk factor for skin cancer, theoretical models suggest that radon exposure can contribute to risk, and this is supported by ecological studies. We sought to confirm or refute an association between long-term exposure to residential radon and the risk for malignant melanoma (MM) and non-melanoma skin cancer (NMSC) using a prospective cohort design and long-term residential radon exposure. METHODS: During 1993 1997, we recruited 57,053 Danish persons and collected baseline information. We traced and geocoded all residential addresses of the cohort members and calculated radon concentrations at each address lived in from 1 January 1971 until censor date. Cox proportional hazards models were used to estimate incidence rate-ratios (IRR) and confidence intervals (CI) for the risk associated with radon exposure for NMSC and MM, and effect modification was assessed. RESULTS: Over a mean follow-up of 13.6 years of 51,445 subjects, there were 3,243 cases of basal cell carcinoma (BCC), 317 cases of squamous cell carcinoma (SCC) and 329 cases of MM. The adjusted IRRs per 100 Bq/m3 increase in residential radon levels for BCC, SCC and MM were 1.14 (95% CI: 1.03, 1.27), 0.90 (95% CI: 0.70, 1.37) and 1.08 (95% CI: 0.77, 1.50), respectively. The association between radon exposure and BCC was stronger among those with higher socio-economic status and those living in apartments at enrollment. CONCLUSION AND IMPACT: Long-term residential radon exposure may contribute to development of basal cell carcinoma of the skin. We cannot exclude confounding from sunlight and cannot conclude on causality, as the relationship was stronger amongst persons living in apartments and non-existent amongst those living in single detached homes. PMID- 26274609 TI - Correction: Biodiversity on the Rocks: Macrofauna Inhabiting Authigenic Carbonate at Costa Rica Methane Seeps. PMID- 26274610 TI - Parkinson's Disease in Saudi Patients: A Genetic Study. AB - Parkinson's disease (PD) is one of the major causes of parkinsonism syndrome. Its characteristic motor symptoms are attributable to dopaminergic neurons loss in the midbrain. Genetic advances have highlighted underlying molecular mechanisms and provided clues to potential therapies. However, most of the studies focusing on the genetic component of PD have been performed on American, European and Asian populations, whereas Arab populations (excluding North African Arabs), particularly Saudis remain to be explored. Here we investigated the genetic causes of PD in Saudis by recruiting 98 PD-cases (sporadic and familial) and screening them for potential pathogenic mutations in PD-established genes; SNCA, PARKIN, PINK1, PARK7/DJ1, LRRK2 and other PD-associated genes using direct sequencing. To our surprise, the screening revealed only three pathogenic point mutations; two in PINK1 and one in PARKIN. In addition to mutational analysis, CNV and cDNA analysis was performed on a subset of patients. Exon/intron dosage alterations in PARKIN were detected and confirmed in 2 cases. Our study suggests that mutations in the ORF of the screened genes are not a common cause of PD in Saudi population; however, these findings by no means exclude the possibility that other genetic events such as gene expression/dosage alteration may be more common nor does it eliminate the possibility of the involvement of novel genes. PMID- 26274611 TI - The molecular mechanism of translational control via the communication between the microRNA pathway and RNA-binding proteins. AB - MicroRNAs (miRNAs) are evolutionarily conserved small noncoding RNAs found in most plants and animals. The miRNA pathway regulates posttranscriptional gene expression through the deadenylation and translation repression of target mRNAs. Recent studies revealed that the early step of translation initiation is the target of "pure" translation repression by the miRNA pathway. Moreover, particularly in animals, the miRNA pathway is required for neuronal development, differentiation, and plasticity. In addition, some functions of miRNAs are regulated by RNA-binding proteins (RBPs) in neuronal cells. This review summarizes new insights about the molecular mechanisms of pure translation repression by miRNA pathway and the communication between the miRNA pathway and RBPs in neuronal local translation. PMID- 26274613 TI - Panmictic and Clonal Evolution on a Single Patchy Resource Produces Polymorphic Foraging Guilds. AB - We develop a stochastic, agent-based model to study how genetic traits and experiential changes in the state of agents and available resources influence individuals' foraging and movement behaviors. These behaviors are manifest as decisions on when to stay and exploit a current resource patch or move to a particular neighboring patch, based on information of the resource qualities of the patches and the anticipated level of intraspecific competition within patches. We use a genetic algorithm approach and an individual's biomass as a fitness surrogate to explore the foraging strategy diversity of evolving guilds under clonal versus hermaphroditic sexual reproduction. We first present the resource exploitation processes, movement on cellular arrays, and genetic algorithm components of the model. We then discuss their implementation on the Nova software platform. This platform seamlessly combines the dynamical systems modeling of consumer-resource interactions with agent-based modeling of individuals moving over a landscapes, using an architecture that lays transparent the following four hierarchical simulation levels: 1.) within-patch consumer resource dynamics, 2.) within-generation movement and competition mitigation processes, 3.) across-generation evolutionary processes, and 4.) multiple runs to generate the statistics needed for comparative analyses. The focus of our analysis is on the question of how the biomass production efficiency and the diversity of guilds of foraging strategy types, exploiting resources over a patchy landscape, evolve under clonal versus random hermaphroditic sexual reproduction. Our results indicate greater biomass production efficiency under clonal reproduction only at higher population densities, and demonstrate that polymorphisms evolve and are maintained under random mating systems. The latter result questions the notion that some type of associative mating structure is needed to maintain genetic polymorphisms among individuals exploiting a common patchy resource on an otherwise spatially homogeneous landscape. PMID- 26274612 TI - Targeting Atp6v1c1 Prevents Inflammation and Bone Erosion Caused by Periodontitis and Reveals Its Critical Function in Osteoimmunology. AB - Periodontal disease (Periodontitis) is a serious disease that affects a majority of adult Americans and is associated with other systemic diseases, including diabetes, rheumatoid arthritis, and other inflammatory diseases. While great efforts have been devoted toward understanding the pathogenesis of periodontitis, there remains a pressing need for developing potent therapeutic strategies for targeting this pervasive and destructive disease. In this study, we utilized novel adeno-associated virus (AAV)-mediated Atp6v1c1 knockdown gene therapy to treat bone erosion and inflammatory caused by periodontitis in mouse model. Atp6v1c1 is a subunit of the V-ATPase complex and regulator of the assembly of the V0 and V1 domains of the V-ATPase complex. We demonstrated previously that Atp6v1c1 has an essential function in osteoclast mediated bone resorption. We hypothesized that Atp6v1c1 may be an ideal target to prevent the bone erosion and inflammation caused by periodontitis. To test the hypothesis, we employed AAV RNAi knockdown of Atp6v1c1 gene expression to prevent bone erosion and gingival inflammation simultaneously. We found that lesion-specific injection of AAV-shRNA Atp6v1c1 into the periodontal disease lesions protected against bone erosion (>85%) and gingival inflammation caused by P. gingivalis W50 infection. AAV mediated Atp6v1c1 knockdown dramatically reduced osteoclast numbers and inhibited the infiltration of dendritic cells and macrophages in the bacteria-induced inflammatory lesions in periodontitis. Silencing of Atp6v1c1 expression also prevented the expressions of osteoclast-related genes and pro-inflammatory cytokine genes. Our data suggests that AAV-shRNA-Atp6v1c1 treatment can significantly attenuate the bone erosion and inflammation caused by periodontitis, indicating the dual function of AAV-shRNA-Atp6v1c1 as an inhibitor of bone erosion mediated by osteoclasts, and as an inhibitor of inflammation through down-regulation of pro-inflammatory cytokine expression. This study demonstrated that Atp6v1c1 RNAi knockdown gene therapy mediated by AAV-shRNA Atp6v1c1 is a promising novel therapeutic approach for the treatment of bone erosion and inflammatory related diseases, such as periodontitis and rheumatoid arthritis. PMID- 26274614 TI - Amyloid-beta Peptide Exacerbates the Memory Deficit Caused by Amyloid Precursor Protein Loss-of-Function in Drosophila. AB - The amyloid precursor protein (APP) plays a central role in Alzheimer's disease (AD). APP can undergo two exclusive proteolytic pathways: cleavage by the alpha secretase initiates the non-amyloidogenic pathway while cleavage by the beta secretase initiates the amyloidogenic pathway that leads, after a second cleavage by the gamma-secretase, to amyloid-beta (Abeta) peptides that can form toxic extracellular deposits, a hallmark of AD. The initial events leading to AD are still unknown. Importantly, aside from Abeta toxicity whose molecular mechanisms remain elusive, several studies have shown that APP plays a positive role in memory, raising the possibility that APP loss-of-function may participate to AD. We previously showed that APPL, the Drosophila APP ortholog, is required for associative memory in young flies. In the present report, we provide the first analysis of the amyloidogenic pathway's influence on memory in the adult. We show that transient overexpression of the beta-secretase in the mushroom bodies, the center for olfactory memory, did not alter memory. In sharp contrast, beta secretase overexpression affected memory when associated with APPL partial loss of-function. Interestingly, similar results were observed with Drosophila Abeta peptide. Because Abeta overexpression impaired memory only when combined to APPL partial loss-of-function, the data suggest that Abeta affects memory through the APPL pathway. Thus, memory is altered by two connected mechanisms-APPL loss-of function and amyloid peptide toxicity-revealing in Drosophila a functional interaction between APPL and amyloid peptide. PMID- 26274616 TI - Correction: Functional Characterization of the Receiver Domain for Phosphorelay Control in Hybrid Sensor Kinases. PMID- 26274615 TI - GNL3L Is a Nucleo-Cytoplasmic Shuttling Protein: Role in Cell Cycle Regulation. AB - GNL3L is an evolutionarily conserved high molecular weight GTP binding nucleolar protein belonging to HSR1-MMR1 subfamily of GTPases. The present investigation reveals that GNL3L is a nucleo-cytoplasmic shuttling protein and its export from the nucleus is sensitive to Leptomycin B. Deletion mutagenesis reveals that the C terminal domain (amino acids 501-582) is necessary and sufficient for the export of GNL3L from the nucleus and the exchange of hydrophobic residues (M567, L570 and 572) within the C-terminal domain impairs this process. Results from the protein-protein interaction analysis indicate that GNL3L interaction with CRM1 is critical for its export from the nucleus. Ectopic expression of GNL3L leads to lesser accumulation of cells in the 'G2/M' phase of cell cycle whereas depletion of endogenous GNL3L results in 'G2/M' arrest. Interestingly, cell cycle analysis followed by BrdU labeling assay indicates that significantly increased DNA synthesis occurs in cells expressing nuclear export defective mutant (GNL3L?NES) compared to the wild type or nuclear import defective GNL3L. Furthermore, increased hyperphosphorylation of Rb at Serine 780 and the upregulation of E2F1, cyclins A2 and E1 upon ectopic expression of GNL3L?NES results in faster 'S' phase progression. Collectively, the present study provides evidence that GNL3L is exported from the nucleus in CRM1 dependent manner and the nuclear localization of GNL3L is important to promote 'S' phase progression during cell proliferation. PMID- 26274617 TI - Retransplant and Medical Therapy for Cardiac Allograft Vasculopathy: International Society for Heart and Lung Transplantation Registry Analysis. AB - Cardiac retransplantation for heart transplant recipients with advanced cardiac allograft vasculopathy (CAV) remains controversial. The International Society for Heart and Lung Transplantation Registry was used to examine survival in adult heart recipients with CAV who were retransplanted (ReTx) or managed medically (MM). Recipients transplanted between 1995 and 2010 who developed CAV and were either retransplanted within 2 years of CAV diagnosis (ReTx) or alive at >=2 years after CAV diagnosis, managed medically (MM), without retransplant, constituted the study groups. Donor, recipient, transplant characteristics and long-term survival were compared. The population included 65 patients in ReTx and 4530 in MM. During a median follow-up of 4 years, there were 24 deaths in ReTx, and 1466 in MM. Survival was comparable at 9 years (55% in ReTx and 51% in MM; p = 0.88). Subgroup comparison suggested survival benefit for retransplant versus MM in patients who developed systolic graft dysfunction. Adjusted predictors for 2-year mortality were diagnosis of CAV in the early era and longer time since CAV diagnosis following primary transplant. Retransplant was not an independent predictor in the model. Challenges associated with retransplantation as well as improved CAV treatment options support the current consensus recommendation limiting retransplant to highly selected patients with CAV. PMID- 26274619 TI - Modeling and Uncertainty Quantification of Vapor Sorption and Diffusion in Heterogeneous Polymers. AB - A high-fidelity model of kinetic and equilibrium sorption and diffusion is developed and exercised. The gas-diffusion model is coupled with a triple sorption mechanism: Henry's law absorption, Langmuir adsorption, and pooling or clustering of molecules at higher partial pressures. Sorption experiments are conducted and span a range of relative humidities (0-95 %) and temperatures (30 60 degrees C). Kinetic and equilibrium sorption properties and effective diffusivity are determined by minimizing the absolute difference between measured and modeled uptakes. Uncertainty quantification and sensitivity analysis methods are described and exercised herein to demonstrate the capability of this modeling approach. Water uptake in silica-filled and unfilled poly(dimethylsiloxane) networks is investigated; however, the model is versatile enough to be used with a wide range of materials and vapors. PMID- 26274618 TI - Probing kinetic drug binding mechanism in voltage-gated sodium ion channel: open state versus inactive state blockers. AB - The kinetics and nonequilibrium thermodynamics of open state and inactive state drug binding mechanisms have been studied here using different voltage protocols in sodium ion channel. We have found that for constant voltage protocol, open state block is more efficient in blocking ionic current than inactive state block. Kinetic effect comes through peak current for mexiletine as an open state blocker and in the tail part for lidocaine as an inactive state blocker. Although the inactivation of sodium channel is a free energy driven process, however, the two different kinds of drug affect the inactivation process in a different way as seen from thermodynamic analysis. In presence of open state drug block, the process initially for a long time remains entropy driven and then becomes free energy driven. However in presence of inactive state block, the process remains entirely entropy driven until the equilibrium is attained. For oscillating voltage protocol, the inactive state blocking is more efficient in damping the oscillation of ionic current. From the pulse train analysis it is found that inactive state blocking is less effective in restoring normal repolarisation and blocks peak ionic current. Pulse train protocol also shows that all the inactive states behave differently as one inactive state responds instantly to the test pulse in an opposite manner from the other two states. PMID- 26274620 TI - Supramolecular Macrostructures of UPy-Functionalized Carbon Nanotubes. AB - Carbon nanotubes (CNTs) are considered excellent materials for the construction of flexible displays due to their nanoscale dimensions and unique physical and chemical properties. By using the recognition properties of 2-ureido 4[1H]pyrimidinone (UPy), a versatile and simple methodology was demonstrated for the construction of macroscopic structures based on UPy-CNT/polymer composites prepared by a combination of two functionalization approaches: 1) covalent attachment of UPy pendants on the multiwalled CNT surface (UPy-MWCNTs) and 2) directed self-assembly of UPy-MWCNTs within polymers bearing UPy pendants (Bis UPy 1 and Bis-UPy 2) by quadruple complementary DDAA-AADD hydrogen-bond recognition (D=donor, A=acceptor). PMID- 26274623 TI - Brainstem Contusion: A Fallacy of GCS-BIS Synchrony. PMID- 26274622 TI - The UK Experience of a Treatment Strategy for Pediatric Metastatic Medulloblastoma Comprising Intensive Induction Chemotherapy, Hyperfractionated Accelerated Radiotherapy and Response Directed High Dose Myeloablative Chemotherapy or Maintenance Chemotherapy (Milan Strategy). AB - BACKGROUND: Historically, the 5-year overall survival (OS) for metastatic medulloblastoma (MMB) was less than 40%. The strategy of post-operative induction chemotherapy (IC) followed by hyperfractionated accelerated radiotherapy (HART) and response directed high dose chemotherapy (HDC) was reported in a single center study to improve 5-year OS to 73%. We report outcomes of this strategy in UK. METHODS: Questionnaires were sent to all 20 UK pediatric oncology primary treatment centers to collect retrospective data on delivered treatment, toxicity and survival with this strategy in children aged 3-19 years with MMB. RESULTS: Between February 2009 and October 2011, 34 patients fulfilled the entry criteria of the original study. The median age was 7 years (range 3-15). Median interval from surgery to HART was 109 versus 85 days in the original series. The incidence of grade 3 or 4 hematological toxicities with IC and HDC was 83-100%. All 16 patients who achieved complete response by the end of the regimen remain in remission but only three of 18 patients with lesser responses are still alive (P < 0.0001). With a median follow-up of 45 months for survivors, the estimated 3 year OS is 56% (95% CI 38, 71). This result is outside the 95% CI of the original study results and encompasses the historical survival result of 40%. CONCLUSION: Within the limits of statistical significance, we did not replicate the improved survival results reported in the original series. The reasons include differences in patient sub-groups and protocol administration. International randomized phase III studies are needed. PMID- 26274624 TI - Inadvertent Neuraxial Anesthesia in a Patient With an Intracranial Space occupying Lesion. PMID- 26274625 TI - Is NIRS-based Cerebral Oximetry Sufficient Monitoring Modality During ICG Utilization in CEA? PMID- 26274626 TI - The Neurobiology of Anesthetic Emergence. AB - Achieving a smooth and rapid emergence from general anesthesia is of particular importance for neurosurgical patients and is a clinical goal for neuroanesthesiologists. Recent data suggest that the process of emergence is not simply the mirror image of induction, but rather controlled by distinct neural circuits. In this narrative review, we discuss (1) hysteresis, (2) the concept of neural inertia, (3) the asymmetry between the neurobiology of induction and emergence, and (4) recent attempts at actively inducing emergence. PMID- 26274627 TI - Using warnings to reduce categorical false memories in younger and older adults. AB - Warnings about memory errors can reduce their incidence, although past work has largely focused on associative memory errors. The current study sought to explore whether warnings could be tailored to specifically reduce false recall of categorical information in both younger and older populations. Before encoding word pairs designed to induce categorical false memories, half of the younger and older participants were warned to avoid committing these types of memory errors. Older adults who received a warning committed fewer categorical memory errors, as well as other types of semantic memory errors, than those who did not receive a warning. In contrast, young adults' memory errors did not differ for the warning versus no-warning groups. Our findings provide evidence for the effectiveness of warnings at reducing categorical memory errors in older adults, perhaps by supporting source monitoring, reduction in reliance on gist traces, or through effective metacognitive strategies. PMID- 26274629 TI - Advances in functional neurosurgery for Parkinson's disease. AB - Functional neurosurgery for Parkinson's disease has become a mainstream concept with DBS as the prime modality. This article reviews the latest and, in the eyes of the authors, the most important developments in DBS, lesioning and gene therapy. In DBS, emerging advances have focused on the timing of surgery relative to disease duration and severity, and new targets, technologies, and equipment. For lesions, new ultrasound techniques are emerging based on successes in other movement disorders. Gene and cellular therapies, including stem cells, remain only in the research realm. PMID- 26274628 TI - Variability of structurally constrained and unconstrained functional connectivity in schizophrenia. AB - Spatial variation in connectivity is an integral aspect of the brain's architecture. In the absence of this variability, the brain may act as a single homogenous entity without regional specialization. In this study, we investigate the variability in functional links categorized on the basis of the presence of direct structural paths (primary) or indirect paths mediated by one (secondary) or more (tertiary) brain regions ascertained by diffusion tensor imaging. We quantified the variability in functional connectivity using an unbiased estimate of unpredictability (functional connectivity entropy) in a neuropsychiatric disorder where structure-function relationship is considered to be abnormal; 34 patients with schizophrenia and 32 healthy controls underwent DTI and resting state functional MRI scans. Less than one-third (27.4% in patients, 27.85% in controls) of functional links between brain regions were regarded as direct primary links on the basis of DTI tractography, while the rest were secondary or tertiary. The most significant changes in the distribution of functional connectivity in schizophrenia occur in indirect tertiary paths with no direct axonal linkage in both early (P=0.0002, d=1.46) and late (P=1*10(-17), d=4.66) stages of schizophrenia, and are not altered by the severity of symptoms, suggesting that this is an invariant feature of this illness. Unlike those with early stage illness, patients with chronic illness show some additional reduction in the distribution of connectivity among functional links that have direct structural paths (P=0.08, d=0.44). Our findings address a critical gap in the literature linking structure and function in schizophrenia, and demonstrate for the first time that the abnormal state of functional connectivity preferentially affects structurally unconstrained links in schizophrenia. It also raises the question of a continuum of dysconnectivity ranging from less direct (structurally unconstrained) to more direct (structurally constrained) brain pathways underlying the progressive clinical staging and persistence of schizophrenia. PMID- 26274630 TI - Potential application of corn starch edible films with spice essential oils for the shelf life extension of red meat. AB - AIM: To investigate the effect of corn starch (CS) edible films with spice oils on the stability of raw beef during refrigerated storage. METHODS AND RESULTS: The antimicrobial properties of corn starch films containing 0-4.0% (w/v) ratios of clove (CL) and cinnamon (CI) essential oils (EOs) were tested against seven meat spoilage organisms by zone inhibition test. Effects of CS films containing 3% CL or CI or a mixture of CL + CI were also tested in raw beef stored at 4 degrees C. Meat samples were analysed for pH, microbial counts, colour values and Thiobarbituric acid reactive substances (TBARS) values for a period of 15 days. CS films with CL + CI resulted in a significant reduction in microbial populations in the meat samples and also improved meat colour stability at the end of storage period. CONCLUSIONS: The incorporation of spice EOs in CS films may provide antimicrobial and antioxidant activities that could improve the stability of raw meat. SIGNIFICANCE AND IMPACT OF THE STUDY: Results from this study may be applied in meat industries as an additional barrier to control microbial spoilage as well as lipid oxidation in meat products. PMID- 26274631 TI - Molecular screening of microbial communities for candidate indicators of multiple metal impacts in marine sediments from northern Australia. AB - Coastal sediments accumulate metals from anthropogenic sources and as a consequence industry is required to monitor sediment health. The total concentration of a metal does not necessarily reflect its potential toxicity or biological impact, so biological assessment tools are useful for monitoring. Rapid biological assessment tools sensitive enough to detect relatively small increases in metal concentrations would provide early warning of future ecosystem impact. The authors investigated in situ populations of Archaea and Bacteria as potential tools for rapid biological assessment in sediment at 4 northern Australian coastal locations over 2 yr, in both wet and dry seasons. The 1 M HCl extractable concentrations of metals in sediment were measured, and Archaeal and Bacterial community profiles were obtained by next-generation sequencing of sediment deoxyribonucleic acid (DNA). Species response curves were used to identify several taxonomic groups with potential as biological indicators of metal impact. Spatial variation, sediment grain size, water depth, and dissolved oxygen also correlated with microbial population shifts. Seasonal variation was less important than geographic location. Metal-challenge culture trials supported the identification of metal-resistant and -sensitive taxa. In situ Archaea and Bacteria are potentially sensitive indicators for changes in bioavailable concentrations of metals; however, the complexity of the system suggests it is important to identify metal-specific functional genes that may be informed by these sequencing surveys, and thus provide a useful addition to identity-based assays. PMID- 26274632 TI - Re: Da Silva AS, Digesu GA, Dell'Utri C, Fritsch H, Piffarotti P, Khullar V. Do ultrasound findings of levator ani "Avulsion" correlate with anatomical findings? A multicenter cadaveric study. Neurourol Urodyn. 2015. doi: 10.1002/nau.22781. PMID- 26274633 TI - Special section editorial: Cancer incidence in five continents including Africa. PMID- 26274634 TI - Silica microwire-based interferometric electric field sensor. AB - Silica microwire, as an optical waveguide whose diameter is close to or smaller than the wavelength of the guided light, is of great interest because it exhibits a number of excellent properties such as tight confinement, large evanescent fields, and great configurability. Here, we report a silica microwire-based compact photonic sensor for real-time detection of high electric field. This device contains an interferometer with propylene carbonate cladding. Based on the Kerr electro-optic effect of propylene carbonate, the applied intensive transient electric field can change the refractive index of propylene carbonate, which shifts the interferometric fringe. Therefore, the electric field could be demodulated by monitoring the fringe shift. The sensor was successfully used to detect alternating electric field with frequency of 50 Hz and impulse electric field with duration time of 200 MUs. This work lays a foundation for future applications in electric field sensing. PMID- 26274635 TI - Highly efficient cascaded amplification using Pr(3+)-doped mid-infrared chalcogenide fiber amplifiers. AB - We computationally investigate cascaded amplification in a three-level mid infrared (IR) Pr(3+)-doped chalcogenide fiber amplifier. The overlap of the cross sections in the transitions (3)H(6)->(3)H(5) and (3)H(5)->(3)H(4) enable both transitions to simultaneously amplify a single wavelength in the range between 4.25 MUm and 4.55 MUm. High gain and low noise are achieved simultaneously if the signal is at 4.5 MUm. We show that 45% of pump power that is injected at 2 MUm can be shifted to 4.5 MUm. The efficiency of using a mid-IR fiber amplifier is higher than what can be achieved by using mid-IR supercontinuum generation, which has been estimated at 25%. This mid-IR fiber amplifier can be used in conjunction with quantum cascade lasers to obtain a tunable, high-power mid-IR source. PMID- 26274636 TI - Exfoliated layers of black phosphorus as saturable absorber for ultrafast solid state laser. AB - High-quality black phosphorus (BP) saturable absorber mirror (SAM) was successfully fabricated with few-layered BP (phosphorene). By employing the prepared phosphorene SAM, we have demonstrated ultrafast pulse generation from a BP mode-locked bulk laser for the first time to our best knowledge. Pulses as short as 6.1 ps with an average power of 460 mW were obtained at the central wavelength of 1064.1 nm. Considering the direct and flexible band gap for different layers of phosphorene, this work may provide a possible method for fabricating BP SAM to achieve ultrafast solid-state lasers in IR and mid-IR wavelength region. PMID- 26274637 TI - High-speed continuous-variable quantum key distribution without sending a local oscillator. AB - We report a 100-MHz continuous-variable quantum key distribution (CV-QKD) experiment over a 25-km fiber channel without sending a local oscillator (LO). We use a "locally" generated LO and implement with a 1-GHz shot-noise-limited homodyne detector to achieve high-speed quantum measurement, and we propose a secure phase compensation scheme to maintain a low level of excess noise. These make high-bit-rate CV-QKD significantly simpler for larger transmission distances compared with previous schemes in which both LO and quantum signals are transmitted through the insecure quantum channel. PMID- 26274638 TI - Self-starting ultrafast fiber lasers mode-locked with alcohol. AB - We report a novel saturable absorber (SA) based on anhydrous alcohol for mode locked fiber lasers (MLFLs). The SA is an optical ferrule with one alcoholic end facet sealed by a polyethylene (PE) film. Its modulation depth is measured to be 5.9%. Also, a self-starting MLFL using such an alcohol-SA has been demonstrated to generate 972-fs pulses at 1594.6 nm. The single pulse energy is up to 1.8 nJ with the repetition rate of 20.97 MHz, and the signal-to-noise ratio (SNR) is higher than 50 dB. The MLFL exhibits the performance of self-starting, good stability, and high pulse energy. Such a cost-effective and easily-prepared SA with high damage threshold may find wide applications for ultrafast lasers. Besides, it may arouse wide considerations of the mode-locking function of organic liquids for ultrafast lasers. PMID- 26274639 TI - Noise suppression in coherent population-trapping atomic clock by differential magneto-optic rotation detection. AB - We propose and investigate a scheme for differential detection of the magneto optic rotation (MOR) effect, where a linearly polarized bichromatic laser field is coherent population-trapping (CPT)-resonant with alkali atoms, and discuss the application of this effect to CPT-based atomic clocks. The results of our study indicate that laser noise in a vertical cavity surface-emitting laser-based CPT atomic clock can be effectively suppressed by the proposed scheme. The proposed scheme promises to realize a packaged MOR-CPT atomic clock that has significantly better frequency stability coupled with similar power consumption, volume, and cost when compared with currently available packaged CPT atomic clocks. PMID- 26274640 TI - Spin-dependent diffraction of evanescent waves by subwavelength gratings. AB - We present a way to observe the spin-to-orbital conversion phenomenon. A spinning evanescent wave can be asymmetrically transformed into propagation waves through one certain diffraction order by a periodical subwavelength grating. By detecting diffraction field distribution behind the grating, we observed spin-dependent diffraction patterns. Furthermore, replacing the periodical grating by a Fibonacci grating, we can simultaneously observe multiple order diffractions of a spin evanescent wave. In this case, the multiple diffraction beams can interfere with each other behind the quasi-periodical grating to form asymmetric interference patterns. Our work provides another way toward the realization of spin-to-orbital conversion of light. PMID- 26274641 TI - How planar optical waves can be made to climb dielectric steps. AB - We show how to optically connect guiding layers at different elevations in a 3-D integrated photonic circuit. Transfer of optical power carried by planar, semi guided waves is possible without reflections or radiation losses, and over large vertical distances. This functionality is realized through simple step-like folds of high-contrast dielectric slab waveguides, in combination with oblique wave incidence, and fulfilling a resonance condition. Radiation losses vanish, and polarization conversion is suppressed for TE wave incidence beyond certain critical angles. This can be understood by fundamental arguments resting on a version of Snell's law. The two 90 degrees corners of a step act as identical partial reflectors in a Fabry-Perot-like resonator setup. By selecting the step height, i.e., the distance between the reflectors, one realizes resonant states with full transmission. Rigorous quasi-analytical simulations for typical silicon/silica parameters demonstrate the functioning. Combinations of several step junctions can lead to other types of optical on-chip connects, e.g., U-turn- or bridge-like configurations. PMID- 26274642 TI - Tailoring of spectral response and spatial field distribution with corrugated photonic crystal slab. AB - We report a new physical mechanism for simultaneous tuning of quality factors, spectral responses, and field distributions in photonic crystal slabs through removal of polarization mode degeneracy using a lattice of elliptical nano-holes. The quality factors in these structures can become higher than those obtained with much smaller circular nano-holes. Furthermore, the modes can be superimposed by either rotating or morphing the elliptical nano-holes into a corrugated grating. These findings will enable improved radiation-matter interaction in optical, microwave, and THZ frequencies along with enhanced opto-acoustic coupling. PMID- 26274643 TI - Carrier-envelope phase-stable spatiotemporal light bullets. AB - We present an extensive experimental investigation of the self-focusing and filamentation of intense 90 fs, 1.8 MUm, carrier-envelope phase-stable laser pulses in fused silica in the anomalous group velocity dispersion region. Spectral measurements in a wedge-shaped sample uncover dynamics of spectral broadening, which captures the evolution of third-harmonic, resonant radiation, and supercontinuum spectra as a function of the propagation distance with unprecedented detail. The relevant events of spectral broadening are linked to the formation and propagation dynamics of spatiotemporal light bullets as measured by a three-dimensional imaging technique. We also show that at a higher input power, the light bullet splits into two bullets, which retain characteristic O-shaped spatiotemporal intensity distributions and propagate with different group velocities. Finally, we demonstrate that the light bullets have a stable carrier-envelope phase that is preserved even after the bullet splitting event, as verified by f-2f interferometric measurements. PMID- 26274644 TI - UV-curable silicate phosphor planar films printed on glass substrate for white light-emitting diodes. AB - We suggest a simple way of forming a nonconventional remote phosphor layer for white light-emitting diodes. A printing technology using a paste consisting of yellow (Ba,Sr,Ca)(2)SiO(4):Eu(2+) silicate phosphor and ultraviolet (UV)-curable polymer is applied to form solid planar films on a common soda lime silicate glass substrate through UV radiation. Relative content of the phosphor was adjusted for the best dispersion of the phosphor particles in the polymer matrix with better emission and luminescence performance. As a result, the 70 wt. % phosphor-embedded film has a luminous efficacy of ~70.1 lm/W at 200 mA. PMID- 26274645 TI - Room-temperature magnetic gradiometry with fiber-coupled nitrogen-vacancy centers in diamond. AB - Differential optical detection of a magnetic resonance induced in nitrogen vacancy (NV) centers in diamond is shown to enable a high-spatial-resolution room temperature magnetic-field gradiometry on a fiber platform. An ultracompact design of this fiber-based solid-state magnetic gradiometer is achieved by integrating an NV-diamond magnetic sensor with a two-fiber opto-microwave interface, which couples NV centers to microwave and optical fields, used to resonantly drive and interrogate the spin of NV centers. PMID- 26274646 TI - Experimental demonstration of laser damage caused by interface coupling effects of substrate surface and coating layers. AB - The laser damage resistance of the coatings for high-power laser systems depends greatly on the surface quality of the substrate. In our work, experimental approaches were employed to understand the interface coupling effect of the substrate surface and coatings on the laser resistance of the coatings. A 1064 nm anti-reflection (AR) coating was deposited by an e-beam coater onto fused silica with and without micro-scale pits (structural defects). The micro-scale pits were precisely fabricated by femtosecond laser processing to prevent the emergence of subsurface cracks. Different deposition temperatures were characterized in order to verify the intensity of the interface coupling effect of the substrate and coating layers. Our experimental results indicate that impurities that are introduced in the finishing process, shifted to the substrate surface, and aggregated during the heating process, play a much more crucial role than structural defects (length: ~7 MUm; width: ~3 MUm; depth: ~0.8 MUm) in the laser-induced damage process. By effectively reducing the intensity of the interface coupling effect, the e-beam AR coatings, whose laser-induced damage resistance was closed to the bare substrate, was prepared. PMID- 26274647 TI - Spontaneous creation and annihilation of temporal cavity solitons in a coherently driven passive fiber resonator. AB - We report on the experimental observation of spontaneous creation and annihilation of temporal cavity solitons (CSs) in a coherently driven, macroscopic optical fiber resonator. Specifically, we show that CSs are spontaneously created when the frequency of the cavity driving field is tuned across a resonance, and that they can individually disappear at different stages of the scan. In contrast to previous experiments in monolithic microresonators, we are able to identify these dynamics in real time, thanks to the macroscopic dimensions of our resonator. Our experimental observations are in excellent agreement with numerical simulations. We also discuss the mechanisms responsible for the one-by-one disappearance of CSs. PMID- 26274648 TI - Laguerre-Gauss beams versus Bessel beams showdown: peer comparison. AB - We present for the first time a comparison under similar circumstances between Laguerre-Gauss beams (LGBs) and Bessel beams (BB), and show that the former can be a better option for many applications in which BBs are currently used. By solving the Laguerre-Gauss differential equation in the asymptotic limit of a large radial index, we find the parameters to perform a peer comparison, showing that LGBs can propagate quasi-nondiffracting beams within the same region of space where the corresponding BBs do. We also demonstrate that LGBs, which have the property of self-healing, are more robust in the sense that they can propagate further than BBs under similar initial conditions. PMID- 26274649 TI - Highly stable digital holographic microscope using Sagnac interferometer. AB - Interferometric microscopy has grown into a very potent tool for quantitative phase imaging of biological samples. Among the interfermetric methods, microscopy by digital holography is one of the most effective techniques, especially for studying dynamics of cells. Imaging of cell fluctuations requires digital holographic setups with high temporal stability. Common path setups in which the object and the reference beams encounter the same set of optical elements provide better temporal stability compared to two-beam setups. Here, we present a compact, easy-to-implement, common path digital holographic microscope based on Sagnac interferometer geometry. The microscope is implemented using a diode laser module employing a CCD array or a webcam sensor to record holograms. The system was tested for three-dimensional imaging capability, numerical focusing ability, and temporal stability. Sub-nanometer temporal stability without external vibration isolation components was obtained in both cases. The higher temporal stability makes the microscope compatible to image cell fluctuations, which is demonstrated by imaging the oscillation of the cell membrane of human red blood cells. PMID- 26274650 TI - 1.1-MUm InAs/GaAs quantum-dot light-emitting transistors grown by molecular beam epitaxy. AB - In this Letter, we report the enhanced radiative recombination output from an AlGaAs/GaAs heterojunction bipolar transistor with InAs quantum dots embedded in the base region to form a quantum-dot light-emitting transistor (QDLET) grown by molecular beam epitaxy systems. For the device with a 100 MUm*100 MUm emitter area, we demonstrate the dual output characteristics with an electrical output and an optical output when the device is operating in the common-emitter configuration. The quantum-dot light-emitting transistor exhibits a base recombination radiation in the near-infrared spectral range with a dominant peak at lambda of 1100 nm. PMID- 26274651 TI - Optimization of spatial acquisition systems for low-light-level robustness in space optical communications. AB - The channel establishment in space optical communications relies on the Acquisition, Tracking, and Pointing (ATP) systems to initially acquire and then stably track the beacon beam. However, insufficient optical power may lead to unstable acquisition or even acquisition failure. In this Letter, we describe the mechanisms causing the instability, and then propose an approach to constrain the acquisition velocity. The approach is based on velocity prediction obtained from the light spot centroids and angle measurement data. Theoretical and experimental results show that the acceptable minimum optical power for acquisition decreases by 5.5 dB after optimization, which effectively enhances the acquisition system's robustness under low-light-level conditions. This approach improves the adaptability of satellite-ground optical communications and also has practical value for deep-space optical communications. PMID- 26274652 TI - Optimal generation of high harmonics in the water-window region by synthesizing 800-nm and mid-infrared laser pulses. AB - We propose a method to optimally synthesize a strong 800-nm Ti:sapphire laser pulse and a relatively weak mid-infrared laser pulse to enhance harmonic yields in the water-window region. The required wavelength of the mid-infrared laser is varied from about 2.0 to 3.2 MUm. The optimized waveforms generate comparable harmonic yields as the waveforms proposed in [Sci. Rep.4, 7067 (2014)], but with much weaker intensity for the mid-infrared laser. This method provides an alternative scheme based on the available laser technology to help realize tabletop light source in the water-window region by high-order harmonic generation. PMID- 26274653 TI - Second-harmonic generation interferometry in magnetic-dipole nanostructures. AB - We present the experimental studies on optical second-harmonic generation from nanostructures exhibiting magnetic dipole resonances in the visible spectral range. "Nanosandwiches" of the composition Au/MgF(2)/Au with the average disk diameter of 140 nm are packed in a square lattice with the period of 400 nm. We show that at normal incidence, the intensity of the second-harmonic (SH) wave generated by the array of nanostructures increases by an order of magnitude as the excitation wavelength approaches the magnetic-dipole resonance, while the phase of the SH wave experiences a shift up to 330 degrees . Based on the phenomenological description of the SH process, the observed effects indicate the dominant role of the nonlinear magnetic-dipole polarization driven by the chi(emm) susceptibility in SH generation in "nanosandwiches." PMID- 26274654 TI - High-beam quality, high-efficiency laser based on fiber with heavily Yb(3+)-doped phosphate core and silica cladding. AB - We have fabricated and tested a composite fiber with an Yb(3+)-doped phosphate glass core and silica cladding. Oscillation with a slope efficiency of 74% was achieved using core pumping at 976 nm with fiber lengths of 48-90 mm in a simple laser configuration, where the cavity was formed by a high-reflectivity Bragg grating and the cleaved fiber end. The measured M(2) factors were as low as 1.05 1.22 even though the fiber was multimode at the lasing wavelength. PMID- 26274655 TI - Interferometric velocity measurements through a fluctuating phase boundary using two Fresnel guide stars. AB - Laser optical techniques are widely used for flow measurements as they offer a high spatial and velocity resolution. However, undisturbed optical access to the measurement volume is desired. In order to measure through a fluctuating phase boundary, we present the use of adaptive optics. In an experiment, we prove that the Fresnel reflex of a phase boundary can be used as a proper guide star for adaptive velocity measurements with a single optical access. Interferometric flow measurements through a fluctuating phase boundary have been accomplished by a Mach-Zehnder interferometer. PMID- 26274656 TI - In-fiber whispering-gallery-mode resonator fabricated by femtosecond laser micromachining. AB - An in-fiber whispering-gallery-mode resonator fabricated by femtosecond laser micromachining is demonstrated. The cylinder resonator cavity is fabricated by scanning the D-fiber cladding with infrared femtosecond pulses along a cylindrical trace with a radius of 25 MUm and height of 20 MUm. Quality factor on the order of 10(3) is achieved by smoothing the cavity surface with an ultrasonic cleaner, which is mainly limited by the surface roughness of several hundred nanometers. Resonant characteristics and polarization dependence of the proposed resonator are also studied in detail. Our method takes a step forward in the integration of whispering-gallery-mode resonators. PMID- 26274657 TI - Method to evaluate afterpulsing probability in single-photon avalanche diodes. AB - We propose and demonstrate a new method for evaluating the afterpulsing effect in single-photon avalanche photodiodes (SPADs). By analyzing the statistical property of dark count rate, we can quantitatively characterize afterpulsing probability (APP) of a SPAD. In experiment, the temperature-dependent low dark count rate (DCR) distribution becomes non-Poissonian at lower temperature and has higher excess bias as the afterpulsing effect becomes significant. Our work provides a flexible way to examine APP in either single-device or circuit level. PMID- 26274658 TI - High-reflectance La/B-based multilayer mirror for 6.x nm wavelength. AB - We report a hybrid thin-film deposition procedure to significantly enhance the reflectivity of La/B-based multilayer structures. This is of relevance for applications of multilayer optics at 6.7-nm wavelength and beyond. Such multilayers showed a reflectance of 64.1% at 6.65 nm measured at 1.5-degrees off normal incidence at PTB (BESSY-II). This was achieved by a special scheme of La passivation. The La layer was nitridated to avoid formation of the optically unfavorable LaBx compound at the B-on-La interface. To avoid the also undesired BN formation at the La-on-B interface, a time-dosed nitridation at the initial stage was applied. This research revealed a good potential for further increase in the reflectivity of multilayer structures at 6.7 nm. PMID- 26274659 TI - Trapping light into high orbital momentum modes of fiber tapers. AB - A tapered cylindrical dielectric optical waveguide acts as a high quality factor white-light cavity providing high field concentration as well as long optical group delay. It is possible to optimize shape of a lossless taper to suppress reflection of the input light and to achieve infinitely high field concentration. These tapers can be used in sensing and optoelectronics applications instead of conventional microcavities. PMID- 26274660 TI - Anharmonic propagation of two-dimensional beams carrying orbital angular momentum in a harmonic potential. AB - We analytically and numerically investigate an anharmonic propagation of two dimensional beams in a harmonic potential. We pick noncentrosymmetric beams of common interest that carry orbital angular momentum. The examples studied include superposed Bessel-Gauss (BG), Laguerre-Gauss (LG), and circular Airy (CA) beams. For the BG beams, periodic inversion, phase transition, and rotation with periodic angular velocity are demonstrated during propagation. For the LG and CA beams, periodic inversion and variable rotation are still there but not the phase transition. On the whole, the "center of mass" and the orbital angular momentum of a beam exhibit harmonic motion, but the motion of the beam intensity distribution in detail is subject to external and internal torques and forces, causing it to be anharmonic. Our results are applicable to other superpositions of finite circularly asymmetric beams. PMID- 26274661 TI - Arbitrary state of polarization with customized degree of polarization generator. AB - An optical setup able to generate arbitrary states of polarization (SOPs) with customized degree of polarization is presented in this Letter. Compared with the few alternatives existing in literature, it presents an easy-to-build optical setup and leads to a superior performance. In fact, experimental results are presented, providing an accurate control for the generation of SOPs (maximum error of 1.7% and 3.3% for ellipticity and azimuth, respectively) as well as for the associated degree of polarization (full experimental variation from 1 up to 0.003, with a 1.7% maximum error). The system proposed may be useful for different applications, for example, for polarimeters testing, speckle metrology, and biological applications. PMID- 26274662 TI - Phase derivative estimation from a single interferogram using a Kalman smoothing algorithm. AB - We report a technique for direct phase derivative estimation from a single recording of a complex interferogram. In this technique, the interference field is represented as an autoregressive model with spatially varying coefficients. Estimates of these coefficients are obtained using the Kalman filter implementation. The Rauch-Tung-Striebel smoothing algorithm further improves the accuracy of the coefficient estimation. These estimated coefficients are utilized to compute the spatially varying phase derivative. Stochastic evolution of the coefficients is considered, which allows estimating the phase derivative with any type of spatial variation. The simulation and experimental results are provided to substantiate the noise robustness and applicability of the proposed method in phase derivative estimation. PMID- 26274663 TI - Mid-IR femtosecond frequency conversion by soliton-probe collision in phase mismatched quadratic nonlinear crystals. AB - We show numerically that ultrashort self-defocusing temporal solitons colliding with a weak pulsed probe in the near-IR can convert the probe to the mid-IR. A near-perfect conversion efficiency is possible for a high effective soliton order. The near-IR self-defocusing soliton can form in a quadratic nonlinear crystal (beta-barium borate) in the normal dispersion regime due to cascaded (phase-mismatched) second-harmonic generation, and the mid-IR converted wave is formed in the anomalous dispersion regime between lambda=2.2-2.4 MUm as a resonant dispersive wave. This process relies on nondegenerate four-wave mixing mediated by an effective negative cross-phase modulation term caused by cascaded soliton-probe sum-frequency generation. PMID- 26274664 TI - Type IIa Bragg gratings formed in microfibers. AB - In this Letter, Type IIa Bragg gratings are inscribed into microfibers. The large germanium-doped core region of the multimode fiber provides the necessary photosensitivity to form a Type IIa grating when it is drawn down to the microscale. Reducing the diameter of the microfiber due to lower saturate modulation and the amplified tension-strain transformation effect can accelerate the formation of a Type IIa grating. This provides an efficient method for the fabrication of fiber gratings with 800 degrees C temperature resistance. PMID- 26274665 TI - Reflectionless potentials for slow whispering gallery modes in surface nanoscale axial photonic fiber resonators. AB - We consider an optical fiber with a nanoscale variation of the effective fiber radius that supports whispering gallery modes slowly propagating along the fiber, and reveal that the radius variation can be designed to support the reflectionless propagation of these modes. We show that reflectionless modulations can realize control of the transmission amplitude and temporal delay, while enabling close packing due to the absence of cross talk, in contrast to the conventional potentials. PMID- 26274666 TI - Combined supercontinuum source with >200 W power using a 3 * 1 broadband fiber power combiner. AB - We report an incoherently combined near-infrared supercontinuum (SC) source with >200 W output power using a 3*1 broadband fiber power combiner. A broadband fiber power combiner is designed and theoretically investigated. The power transmission efficiencies of light at different wavelengths of the combiner are calculated, and the combiner is verified to be capable of combining broadband sources efficiently. Then a combiner is fabricated. Three ~70 W near-infrared SC sources are constructed and then, using the combiner, a >200 W near-infrared SC source is obtained. Conclusively, using incoherently combining method we can obtain a high-power SC source, and the thermo-management can be realized easily. We believe that this is a suitable method to obtain a higher-power SC source. PMID- 26274667 TI - High-energy noncollinear optical parametric amplifier producing 4 fs pulses in the visible seeded by a gas-phase filament. AB - We report on the design and characterization of a short-pulse-pumped, single stage noncollinear optical parametric amplifier (NOPA) that achieves high pulse energies in the few-cycle pulse regime. Optimal pulse-front tilting and temporal compression of the short (35 fs) pump pulse are achieved using a 4f grating compressor, while spatial chirp at the NOPA crystal is eliminated with proper imaging using a pair of reflective telescopes. Gas-phase filamentation in an open ended argon-filled cell provides a bright, stable seed source with little residual chirp that is suitable for temporal overlap with the short pump pulse without dispersion precompensation. Two seeding geometries are explored, and pulses as short as 3.5 fs are obtained by seeding with the entire filament bandwidth. Fourier-transform-limited 4 fs pulses are obtained by filtering the IR portion of the spectrum. PMID- 26274668 TI - Femtosecond mode-locked Nd(3+)-doped Ba(Zr,Mg,Ta)O(3) ceramic laser. AB - We have demonstrated continuous wave (CW) laser operation and the first, to the best of our knowledge, sub-200 fs mode-locked laser operation of Nd(3+)-doped Ba(Zr,Mg,Ta)O(3) ceramic. Its disordered crystalline nature exhibits a broad gain bandwidth of 30 nm with a high-emission cross section. It also has higher thermal and mechanical properties than Nd:glass. In CW operation, a maximum output power of 1.5 W under 6.2 W of absorbed pump power was obtained. In mode-locked operation, a pulse duration of 196 fs with an average power of 60 mW was successfully achieved. The laser spectrum straddled both fluorescence peaks of A site and B-site Nd(3+) ions. PMID- 26274669 TI - Look-back-upon tree recurrence method for Geiger-mode avalanche photodiode performance prediction. AB - This Letter, for the first time, proposes the look-back-upon tree recurrence (LTR) method based on the Poisson statistics for discrete time to predict the performance of Geiger-mode avalanche photodiodes with a short dead time. The results of the proposed method correspond to the results of previous methods for diverse input fluxes. The LTR method possesses very low time and space complexity to allow for the real-time analysis of the Geiger-mode avalanche photodiodes' performance over the entire ranges of dead time and input diversity. PMID- 26274670 TI - Vertical optical ring resonators fully integrated with nanophotonic waveguides on silicon-on-insulator substrates. AB - We demonstrate full integration of vertical optical ring resonators with silicon nanophotonic waveguides on silicon-on-insulator substrates to accomplish a significant step toward 3D photonic integration. The on-chip integration is realized by rolling up 2D differentially strained TiO(2) nanomembranes into 3D microtube cavities on a nanophotonic microchip. The integration configuration allows for out-of-plane optical coupling between the in-plane nanowaveguides and the vertical microtube cavities as a compact and mechanically stable optical unit, which could enable refined vertical light transfer in 3D stacks of multiple photonic layers. In this vertical transmission scheme, resonant filtering of optical signals at telecommunication wavelengths is demonstrated based on subwavelength thick-walled microcavities. Moreover, an array of microtube cavities is prepared, and each microtube cavity is integrated with multiple waveguides, which opens up interesting perspectives toward parallel and multi routing through a single-cavity device as well as high-throughput optofluidic sensing schemes. PMID- 26274671 TI - Local excitation of surface plasmon polaritons using nitrogen-vacancy centers. AB - Surface plasmon polaritons (SPPs) are locally excited at silver surfaces using (~100) nanometer-sized nanodiamonds (NDs) with multiple nitrogen-vacancy (NV) centers (~400). The fluorescences from an externally illuminated (at 532 nm) ND and from nearby NDs, which are not illuminated but produce out-of-plane scattering of SPPs excited by the illuminated ND, exhibit distinctly different wavelength spectra, showing short-wavelength filtering due to the SPP propagation loss. The results indicate that NDs with multiple NV centers can be used as efficient subwavelength SPP sources in planar integrated plasmonics for various applications. PMID- 26274672 TI - Giant thermo-optical relaxation oscillations in millimeter-size whispering gallery mode disk resonators. AB - In this Letter, we show that giant thermo-optical oscillations can be triggered in millimeter (mm)-size whispering gallery mode (WGM) disk resonators when they are pumped by a resonant continuous-wave laser. Our resonator is an ultrahigh-Q barium fluoride cavity that features a positive thermo-optic coefficient and a negative thermo-elastic coefficient. We demonstrate for the first time, to our knowledge, that the complex interplay between these two thermic coefficients and the intrinsic Kerr nonlinearity yields very sharp slow-fast relaxation oscillations with a slow timescale that can be exceptionally large, typically of the order of 1 s. We use a time-domain model to gain understanding into this instability, and we find that both the experimental and theoretical results are in excellent agreement. The understanding of these thermal effects is an essential requirement for every WGM-related application and our study demonstrates that even in the case of mm-size resonators, such effects can still be accurately analyzed using nonlinear time-domain models. PMID- 26274673 TI - Simple method to enhance terahertz radiation from femtosecond laser filament array with a step phase plate. AB - In this work, we experimentally demonstrate a 200% enhancement of terahertz (THz) wave amplitude generated by femtosecond laser filamentation in air. The experimental setup simply uses a semicircular phase plate to generate two parallel filaments. Temporally overlapped THz pulses from two filaments coherently add up, giving rise to significant enhancement of the THz pulse amplitude. It has been foreseen that further enhancement would be achieved if the design of phase plates could be optimized to generate a filament array. This simple method makes full use of the laser energy and could potentially open a new approach to remotely enhance the THz emission in air. PMID- 26274674 TI - Toward a new radiative-transfer-based model for remote sensing of terrestrial surface albedo. AB - This Letter formulates a simple yet accurate radiative-transfer-based theoretical model to characterize the fraction of radiation reflected by terrestrial surfaces. Emphasis is placed on the concept of inhomogeneous distribution of the diffuse sky radiation function (DSRF) and multiple interaction effects (MIE). Neglecting DSRF and MIE produces a -1.55% mean relative bias in albedo estimates. The presented model can elucidate the impact of DSRF on the surface volume scattering and geometry-optical scattering components, respectively, especially for slant illuminations with solar zenith angles (SZA) larger than 50 degrees . Particularly striking in the comparisons between our model and ground-based observations is the achievement of the agreement level, indicating that our model can effectively resolve the longstanding issue in accurately estimating albedo at extremely large SZAs and is promising for land-atmosphere interactions studies. PMID- 26274675 TI - Single-longitudinal-mode Er:GGG microchip laser operating at 2.7 MUm. AB - We reported on a diode-end-pumped single-longitudinal-mode microchip laser using a 600-MUm-thick Er:GGG crystal at ~2.7 MUm, generating a maximum output power of 50.8 mW and the maximum pulsed energy of 0.306 mJ, with repetition rates of pumping light of 300, 200, and 100 Hz, respectively. The maximum slope efficiency of the laser was 20.1%. The laser was operated in a single-longitudinal mode centered at about 2704 nm with a FWHM of 0.42 nm. The laser had a fundamental beam profile and the beam quality parameter M(2) was measured as 1.46. These results indicate that the Er:GGG microchip laser is a potential compact mid infrared laser source. PMID- 26274676 TI - In situ fabrication of a tunable microlens. AB - We demonstrate an optofluidic variable-focus microlens formed by a solid polydimethylsiloxane (PDMS) meniscus channel wall and a tunable liquid lens body. A novel method for in situ fabrication of the meniscus channel wall is developed by introducing liquid PDMS prepolymer into a microchannel followed by curing. Three-light manipulation techniques including tunable optical focusing, collimating, and diverging are realized by varying the refractive index (RI) of liquid lens body. Also, we present an absorption measurement of methylene blue (MB) with a collimated probing light, achieving a detection limit of 0.25 MUM by using a 5-mm-long detection cell. PMID- 26274677 TI - Reconfigurable semiconductor laser networks based on diffractive coupling. AB - Networks of optical emitters are highly sought-after, both for fundamental investigations as well as for various technological applications. We introduce and implement a novel scheme, based on diffractive optical coupling, allowing for the coupling of large numbers of optical emitters with adjustable weights. We demonstrate its potential by coupling emitters of a 2D array of semiconductor lasers with significant efficiency. PMID- 26274678 TI - Polarization-sensitive optical coherence tomography system tolerant to fiber disturbances using a line camera. AB - This Letter presents a spectral-domain, polarization-sensitive optical coherence tomography (PS-OCT) system, where the light collection from the two arms of the interferometer is performed exclusively using single-mode fibers and couplers, and the two orthogonal polarization components are sequentially detected by a single line camera. Retardance measurements can be affected by polarimetric effects because of fiber birefringence and diattenuation in fiber couplers. This configuration bypasses such issues by performing polarization selection before the collection fiber through the combination of a polarization rotator and a linear polarizer. Retardance calibration is achieved with a Berek compensator. Similar net retardance maps of a birefringent phantom are obtained for two different settings of induced fiber birefringence, effectively demonstrating the tolerance of the configuration to fiber-based disturbances. PMID- 26274679 TI - Lens-free spectral light-field fusion microscopy for contrast- and resolution enhanced imaging of biological specimens. AB - A lens-free spectral light-field fusion microscopy (LSLFM) system is presented for enabling contrast- and resolution-enhanced imaging of biological specimens. LSLFM consists of a pulsed multispectral lens-free microscope for capturing interferometric light-field encodings at various wavelengths, and Bayesian-based fusion to reconstruct a fused object light-field from the encodings. By fusing unique object detail information captured at different wavelengths, LSLFM can achieve improved resolution, contrast, and signal-to-noise ratio (SNR) over a single-channel lens-free microscopy system. A five-channel LSLFM system was developed and quantitatively evaluated to validate the design. Experimental results demonstrated that the LSLFM system provided SNR improvements of 6-12 dB, as well as a six-fold improvement in the dispersion index (DI), over that achieved using a single-channel, resolution-enhancing lens-free deconvolution microscopy system or its multi-wavelength counterpart. Furthermore, the LSLFM system achieved an increase in numerical aperture (NA) of ~16% over a single channel resolution-enhancing lens-free deconvolution microscopy system at the highest resolution wavelength used in the study. Samples of Staurastrum paradoxum, a waterborne algae, and human corneal epithelial cells were imaged using the system to illustrate its potential for enhanced imaging of biological specimens. PMID- 26274680 TI - Cosine light-trapping nanostructures for thin film solar cells. AB - In this Letter, we present a cosine light-trapping texture for thin-film silicon solar cells. The surface texture was numerically demonstrated to exhibit comparable light-trapping performance to the inverted pyramid one, which is classic high-efficiency light-trapping structure. The cosine texture can be directly formed by interference lithography, while the inverted pyramid needs more complicated processing. The proposed structure has the potential to play a key role in thin-film solar cells. PMID- 26274681 TI - Theoretical treatment of the interaction between two-level atoms and periodic waveguides. AB - Light transport in periodic waveguides coupled to two-level atoms is investigated theoretically. By using optical Bloch equations and a photonic modal formalism, we derive a convenient semi-analytical expression for calculating the scattering matrix of single atoms trapped in periodic waveguides. The expression that holds for both photonic and plasmonic waveguides represents a basic building block toward the study of collective effects arising from photon-mediated multi-atom interactions in periodic waveguides. PMID- 26274682 TI - Poly-periodic hole arrays for angle-invariant plasmonic filters. AB - We suggest a plasmonic filter with novel hole arrays for an angle-invariant optical response. The suggested patterns consist of randomly distributed polycrystalline domains in which nano sized holes are arranged with the same period. While the microscopic area of periodicity determines the center wavelength and transmission intensity, the broken periodicity of each domain contributes to restrain the angle dependency. The results increase the possible use of nanohole-based filters in practical area. PMID- 26274683 TI - Far-infrared quasi-monochromatic perfect absorption in a thin GaAs film on gold. AB - We study the far-infrared absorption properties of a thin GaAs film on Au. We show that a 1.2-MUm GaAs film on Au can completely absorb an electromagnetic wave of 7.9 THz and totally reflect the waves of frequencies not very close to 7.9 THz. The uniformity of the layered structure enables observation of a quasi monochromatic, nearly perfect absorption of 96% in a 1.4-MUm GaAs film. The absorption can be high for a wide range of incident angles. PMID- 26274684 TI - Effect of spherical aberration on laser beam self-focusing in the atmosphere. AB - The effect of spherical aberration on the laser beam self-focusing in the atmosphere to assist delivering powerful laser beams from orbit to the ground is studied. It is found that for the small orbital mirror size, a Gaussian beam with negative spherical aberration might be more strongly compressed without filamentation than that without spherical aberration, and its spot size on the ground can be reduced well below the diffraction limit. However, for the large orbital mirror size, spherical aberration will result in an increase of receiver size on the ground. PMID- 26274685 TI - Ultrafast thulium-doped fiber laser mode locked with black phosphorus. AB - We report, for the first time to our knowledge, the usage of black phosphorus (BP) as a saturable absorber for the mode locking of a thulium-doped fiber laser. We have experimentally shown that BP exhibits saturable absorption in the 2 MUm wavelength range and supports ultrashort pulse generation. The saturable absorber was based on mechanically exfoliated BP deposited on a fiber connector tip. The laser was capable of generating 739 fs pulses centered at 1910 nm. Our results show that BP might be considered as a universal broadband saturable absorber that could successfully compete with graphene or other low-dimension nanomaterials. PMID- 26274686 TI - Determination of recombination coefficients for nanocrystalline silicon embedded in hydrogenated amorphous silicon. AB - The spectroscopic pump-probe reflectance method was used to investigate recombination dynamics in samples of nanocrystalline silicon embedded in a matrix of hydrogenated amorphous silicon. We found that the dynamics can be described by a rate equation including linear and quadratic terms corresponding to recombination processes associated with impurities and impurity-assisted Auger ionization, respectively. We determined the values of the recombination coefficients using the initial concentrations method. We report the coefficients of 1.5*10(11) s(-1) and 1.1*10(-10) cm(3) s(-1) for the impurity-assisted recombination and Auger ionization, respectively. PMID- 26274687 TI - Ultra-compact broadband higher order-mode pass filter fabricated in a silicon waveguide for multimode photonics. AB - An ultra-compact and broadband higher order-mode pass filter in a 1D photonic crystal silicon waveguide is proposed and experimentally demonstrated. The photonic crystal is designed for the lower order mode to work in the photonic band gap, while the higher order mode is located in the air band. Consequently, light on the lower order mode is prohibited to pass through the filter, while light on a higher order mode can be converted to a Bloch mode in the photonic crystal and pass through the filter with low insertion loss. As an example, we fabricate a ~15-MUm-long first-order-mode pass filter that filters out the fundamental mode and provides a measured insertion loss of ~1.8 dB for the first order-mode pass signals. The extinction ratio is measured to be around 50 dB (with a variation of +/-10 dB due to the detection limitation of the measurement setup) in the measured wavelength range from 1480 to 1580 nm. Additionally, calculations predict the extinction ratio to be larger than 50 dB in a 170 nm broad bandwidth. PMID- 26274688 TI - High-power, widely tunable, room-temperature picosecond optical parametric oscillator based on cylindrical 5%MgO:PPLN. AB - We report a high-power picosecond optical parametric oscillator (OPO) based on cylindrical MgO:PPLN synchronously pumped by an Yb-fiber laser. The singly resonant OPO is tunable in the near-infrared signal across 1413-1900 nm and mid infrared idler over 2418-4307 nm by angle tuning of the crystal at room temperature. With non-optimized output coupling of ~10%, the OPO simultaneously delivers 2.4 W of signal at 1664 nm and 1.7 W of idler at 2950 nm at an overall extraction efficiency of ~45% with high beam-pointing stability <30 MUrad and <14 MUrad for the signal and idler, respectively. The generated signal and idler exhibit passive power stability better than 1% rms and 0.8% rms over 15 h, respectively, in high beam quality with TEM(00) profile. The extracted signal pulses from the OPO have duration of 15.2 ps with a spectral bandwidth of 0.7 nm, corresponding to a time-bandwidth product of DeltaupsilonDeltatau~1.2. PMID- 26274689 TI - Optical implementation of the generalized Hough transform with totally incoherent light. AB - The generalized Hough transform is a well-established technique for detecting complex shapes in images containing noisy or missing data. We present an efficient optical implementation of this transform using an electrical lens with variable focal length and a rotating pupil mask matching the pattern to be found. The proposed setup works under fully (i.e., both spatially and temporally) incoherent illumination and can handle orientation changes or scale variations in the pattern. Validation experiments showing its real-time application are presented. PMID- 26274690 TI - Low-temperature cross-talk magnetic-field sensor based on tapered all-solid waveguide-array fiber and magnetic fluids. AB - A compact fiber-optic magnetic-field sensor based on tapered all-solid waveguide array fiber (WAF) and magnetic fluid (MF) has been proposed and experimentally demonstrated. The tapered all-solid WAF is fabricated by using a fusion splicer, and the sensor is formed by immersing the tapered all-solid WAF into the MF. The transmission spectra have been measured and analyzed under different magnetic field intensities. Experimental results show that the acquired magnetic-field sensitivity is 44.57 pm/Oe for a linear magnetic-field intensity range from 50 to 200 Oe. All-solid WAF has very similar thermal expansion coefficient for high- and low-refractive-index glasses, so mode profile is not affected by thermal drifts. Also, magnetically induced refractive-index changes into the ferrofluid are of the order of ~5*10(-2), while the corresponding thermally induced refractive-index changes into the ferrofluid are expected to be lower. The temperature response has also been detected, and the temperature-induced wavelength shift perturbation is less than 0.3 nm from temperature of 26.9 degrees C-44 degrees C. The proposed magnetic-field sensor has such advantages as low temperature sensitivity, simple structure, and ease of fabrication. It also indicates that the magnetic-field sensor based on tapered all-solid WAF and MF is helpful to reduce temperature cross-sensitivity for the measurement of magnetic field. PMID- 26274691 TI - Tunable plasmonic resonances based on elliptical annular aperture arrays on conducting substrates for advanced biosensing. AB - Introducing a conducting metal layer and the structural asymmetry to elliptical annular aperture arrays, multiple plasmonic coupled-resonant modes are generated under normal incidence in the visible light range. The electromagnetic fields can be strongly enhanced at resonant modes in this device, which increases the interaction volume of the detected analyte and optical fields; therefore, multiple plamonic coupled modes exhibit higher refractive index sensitivity than as large as 610 nm/RIU. The distinct Fano-like resonance around a wavelength of 681 nm originates from the interference between bonding dipolar and the quadrupolar modes. Due to the excitation of sharp spectral features as narrow as 7 nm, high figure of merits of 94 at the Fano-like dip is obtained in a wide refractive index range of 1.33-1.40. Furthermore, to generate strong Fano-like resonance, the geometric shape of ellipse is selected, which is a good geometric shape candidate compared to the circle shape. This device is promising for biosensing applications with high sensitivity and low limit of detection. PMID- 26274692 TI - Asymmetric optical cryptosystem based on coherent superposition and equal modulus decomposition: comment. AB - I comment on the recent Letter by Cai et al. [Opt. Lett.40, 475 (2015).], in which the authors claimed that the method can resist the special attack. However, I think their attack analysis and algorithm are ill-considered and worth discussing. PMID- 26274693 TI - Computational modeling of optical properties in aluminum nanolayers inserted in ZnO for solar cell electrodes. AB - Numerical simulations were used to study the transmittances (Ts) of ZnO/Al/ZnO (ZAZ) films with Al thicknesses between ~1 and 40 nm. The simulations are validated using previously reported experimental results. Multilayers with Al thicknesses between ~1 and 10 nm are shown to have average Ts between ~75% and 90%, which decreased farther to ~63 and 41% for the Al layer thicknesses of 20 and 40 nm, respectively. Variations in the ZnO thickness between ~10 and 100 nm are shown to have little effect on the optical properties of the model multilayers for a given Al thickness. The reliability of the numerical simulations is tested by comparing them with experimental measurements on films produced using similar interlayer thicknesses. These are also shown to be comparable to the performance characteristics of indium tin oxide (ITO) anodes that are used currently in organic solar cells (OSCs) and organic light emitting diodes (OLEDs). PMID- 26274694 TI - Quasi-3D plasmonic coupling scheme for near-field optical lithography and imaging. AB - Near-field optical imaging and lithography rely on achieving both high resolution and efficient coupling. Particularly conventional near-field scanning optical microscopy (NSOM) suffers from the trade-off between resolution and efficiency. Planar plasmonic lens schemes can partially solve this issue utilizing plasmonic resonances, but the performance is not robust over a large range of sample materials. In this work we show a novel quasi-3D plasmonic scheme to focus light into the extreme subwavelength region in the near field with an efficiency orders higher than NSOM. The superb performance comes from the strong coupling between the localized mode with an off-plane E-field component and the sample being processed. Our scheme can efficiently focus light to a spot with a diameter down to 1/20 of its wavelength, and the coupling efficiency can be as high as 10%. Theoretically, we demonstrate that the FWHM of the focus spot can be 7 nm with an enhancement of about 800 at the UV region. The focusing performance is constantly good over a large variety of materials and the illumination and collection imaging scheme has been demonstrated by simulation. An example design of this quasi-3D coupling scheme is fabricated and its imaging performance is characterized by the apertureless optical near-field measurement. The high coupling efficiency at extreme subwavelength resolution of this quasi-3D coupling scheme opens the door to many applications, such as optical lithography, nanoscale imaging, heat-assisted magnetic recording, plasmon-enhanced Raman spectroscopy, etc. PMID- 26274695 TI - Symmetry recovery for coupled photonic modes with transversal PT symmetry. AB - Typical parity-time (PT) symmetric structures switch from the unbroken to the broken phase when gain increases through an exceptional point. In contrast, we report on systems with the unusual, reverse behavior, where the symmetric phase is recovered after a broken phase. We study this phenomenon analytically and numerically in the simplest possible system, consisting of four coupled modes, and we present potential dielectric and plasmonic implementations. The complex mode merging scheme, with two distinct unbroken PT phases encompassing a broken one, appears for a specific proportion range of the coupling constants. This regime with "inverse" exceptional points is interesting for the design of novel PT devices. PMID- 26274696 TI - Pharmacokinetics and Long-Term Safety and Tolerability of Everolimus in Renal Transplant Recipients Converted From Cyclosporine. AB - BACKGROUND: Conversion from cyclosporine (CsA) to everolimus (EVR) in kidney transplant recipients receiving mycophenolate sodium (MPS) and corticosteroids has been used to reduce CsA associated toxicities. Nevertheless, exposures produced by the initial EVR dose, the steady state pharmacokinetic and long-term safety and tolerability have not been explored in detail. METHODS: Twenty-four stable kidney transplant recipients receiving CSA, MPS, and corticosteroids were converted from CSA to EVR. The initial EVR dose was 3 mg BID. Weekly monitoring of EVR blood concentrations was followed by a full 12 hour pharmacokinetic profile 28 days after conversion. Therapeutic drug monitoring, safety, and tolerability were analyzed during 5 years of follow-up. RESULTS: The study population was relatively young (mean of 42 years) with a predominance of males (62%) and White (67%) recipients of kidneys from living (54%) or deceased (46%) donors. Mean time of the conversion was 61 months after transplantation. In the first 7 patients, the initial EVR dose of 3 mg BID resulted in mean EVR trough blood concentration of 14.7 +/- 3.7 ng/mL at day 7. The initial EVR dose was then reduced to 2 mg BID for the following 17 patients. Four weeks after conversion, mean EVR dose was 1.7 +/- 0.5 mg BID (7 patients were receiving 1 mg BID and 17 were receiving 2 mg BID) resulting in mean EVR trough blood concentration of 4.0 +/- 1.4 ng/mL. Whereas mean maximum concentration (13.4 +/- 2.8 versus 22.9 +/- 7.4 ng/mL, P = 0.003) and mean apparent clearance (232 +/- 79 versus 366 +/- 173 mL/min, P = 0.016) were higher, mean area under the curve (78.2 +/- 22.1 versus 102.5 +/- 38.5 ng.h/mL, P = 0.067) and mean C0 (3.7 +/- 1.3 versus 4.1 +/- 1.5 ng/mL, P = 0.852) were no different comparing patients receiving 1 mg and 2 mg EVR BID. Mean inter-subject variability of area under the curve, trough concentration, and maximum concentration was 38%, 36%, and 38%. EVR treatment was discontinued in 29% of patients due to proteinuria (N = 2), pneumonia (N = 2), dyslipidemia (N = 2), and anemia (N = 1) and MPS dose was reduced in 58% of patients. CONCLUSIONS: The initial 3 mg BID dose produced high EVR trough blood concentrations. The 2 mg BID dose appears to be the appropriate initial dose to provide therapeutic concentrations but still requires initial intensive therapeutic monitoring to achieve and maintain blood concentrations within the therapeutic target concentration. The combination of EVR and full dose MPS has limited long-term tolerability and safety. PMID- 26274702 TI - Foreword. The Future of Sepsis Performance Improvement. PMID- 26274697 TI - Mitochondrial dysfunction and loss of glutamate uptake in primary astrocytes exposed to titanium dioxide nanoparticles. AB - Titanium dioxide (TiO2) nanoparticles are currently the second most produced engineered nanomaterial in the world with vast usage in consumer products leading to recurrent human exposure. Animal studies indicate significant nanoparticle accumulation in the brain while cellular toxicity studies demonstrate negative effects on neuronal cell viability and function. However, the toxicological effects of nanoparticles on astrocytes, the most abundant cells in the brain, have not been extensively investigated. Therefore, we determined the sub-toxic effect of three different TiO2 nanoparticles (rutile, anatase and commercially available P25 TiO2 nanoparticles) on primary rat cortical astrocytes. We evaluated some events related to astrocyte functions and mitochondrial dysregulation: (1) glutamate uptake; (2) redox signaling mechanisms by measuring ROS production; (3) the expression patterns of dynamin-related proteins (DRPs) and mitofusins 1 and 2, whose expression is central to mitochondrial dynamics; and (4) mitochondrial morphology by MitoTracker(r) Red CMXRos staining. Anatase, rutile and P25 were found to have LC50 values of 88.22 +/- 10.56 ppm, 136.0 +/- 31.73 ppm and 62.37 +/- 9.06 ppm respectively indicating nanoparticle specific toxicity. All three TiO2 nanoparticles induced a significant loss in glutamate uptake indicative of a loss in vital astrocyte function. TiO2 nanoparticles also induced an increase in reactive oxygen species generation, and a decrease in mitochondrial membrane potential, suggesting mitochondrial damage. TiO2 nanoparticle exposure altered expression patterns of DRPs at low concentrations (25 ppm) and apoptotic fission at high concentrations (100 ppm). TiO2 nanoparticle exposure also resulted in changes to mitochondrial morphology confirmed by mitochondrial staining. Collectively, our data provide compelling evidence that TiO2 nanoparticle exposure has potential implications in astrocyte mediated neurological dysfunction. PMID- 26274703 TI - Primed for Injury: Cigarette Smokers and Acute Respiratory Distress Syndrome. PMID- 26274704 TI - Ventilator-Associated Events: Are We Missing the Forest for the Trees? PMID- 26274705 TI - Regionalized Critical Care May Be Feasible, But Will It Improve Outcomes? PMID- 26274706 TI - Primary Speciality Intensive Care: Pedagogy, Professionalism, and Patients. PMID- 26274707 TI - Take a Deep Breath-or Not. PMID- 26274708 TI - Can't We All Get Along? PMID- 26274709 TI - Why the Propensity for Propensity Scores? PMID- 26274710 TI - Teamwork in the ICU: From Training Camp to the Super Bowl. PMID- 26274711 TI - Acute Kidney Injury During Extracorporeal Membrane Oxygenation: Timing and Fluid Overload May Be Important Determinants of Outcome. PMID- 26274712 TI - Timing of Therapy in Sepsis: Are Early Antibiotics Important for Prognosis? PMID- 26274713 TI - The Evolution of Sepsis Performance Metrics: From Mortality to Hospital Readmission. PMID- 26274714 TI - Palliative Care in the Neurologic ICU-Are We There Yet? PMID- 26274715 TI - It Seems Like the Resuscitation Happened Ages Ago-Chronic Critical Illness in Children: Digging in for the Long Haul. PMID- 26274716 TI - Hematopoietic Stem Cell Transplantation: Better Data, Better Care? Big Data, Bigger Questions! PMID- 26274717 TI - Action and Reaction: The Role of Catecholamine Agonists and Antagonists in Septic Shock. PMID- 26274718 TI - Is Glibenclamide the New Cool in Cardiopulmonary Resuscitation? PMID- 26274719 TI - Hypothermia Reduces the Cerebral Blood Flow Threshold Critical to Reestablish Neuronal Membrane Potential. PMID- 26274720 TI - Purposeful Repurposing: Unexpected but Not Necessarily Unwelcome Effects of Dexmedetomidine. PMID- 26274722 TI - Noninvasive Ventilation Plus Extracorporeal CO2 Removal in High-Risk Conditions: A Forthcoming Tool? PMID- 26274721 TI - Dexmedetomidine Attenuates Bilirubin-Induced Lung Alveolar Epithelial Cell Death In Vitro and In Vivo. AB - OBJECTIVE: To investigate bilirubin-induced lung alveolar epithelial cell injury together with the protection afforded by dexmedetomidine. DESIGN: Prospective, randomized, controlled study. SETTING: Research laboratory. SUBJECTS: Sprague Dawley rats. INTERVENTIONS: Alveolar epithelial A549 cell lines were cultured and received bilirubin (from 0 to 160 MUM) to explore the protective pathway of dexmedetomidine on bilirubin-induced alveolar epithelial cell injury assessed by immunochemistry and flow cytometry. Sprague-Dawley rats were subjected to common bile duct ligation surgery to explore the protective effect of dexmedetomidine on hyperbilirubinemia-induced alveolar epithelial cell injury and respiratory failure in comparison with the Sham (subjected to the surgery procedure but without bile duct ligation) or dexmedetomidine control (only received intraperitoneal injection of dexmedetomidine). MEASUREMENTS AND MAIN RESULTS: In vitro, dexmedetomidine reversed the collapse of mitochondrial membrane potential (Deltapsim), upregulation of cytochrome C, B cell leukemia 2 associated X protein, and cleaved-caspase 3 and 9 in A549 epithelial cells with bilirubin challenge. Furthermore, dexmedetomidine reversed the arrest of cell cycle and the downregulation of the transforming growth factorbeta, phosphorylated mammalian target of rapamycin, and p42/44 mitogen-activated protein kinase induced by bilirubin. In vivo, pulmonary edema and inflammation were found after common bile duct ligation. Bilirubin and PaCO2 were significantly increased, and oxygen (PaO2) was significantly decreased in the blood of common bile duct ligation rats from the postsurgery day 7 to day 21 when compared with those in the sham controls, respectively (p < 0.01). Daily intraperitoneal injection of dexmedetomidine significantly alleviated the lung edema and injury and prevented respiratory failure. CONCLUSION: Our data both in vitro and in vivo demonstrated that dexmedetomidine protected alveolar epithelial cell from bilirubin-induced injury. Dexmedetomidine may be a good choice of anesthetic/sedative for patients with chronic liver disease during the perioperative period. PMID- 26274723 TI - The authors reply. PMID- 26274724 TI - The Effect of Advanced Directive Restriction. PMID- 26274725 TI - The authors reply. PMID- 26274726 TI - Neutrophil Gelatinase-Associated Lipocalin as an Early Prognostic Biomarker in Acute Kidney Injury Following Cardiac Surgery. PMID- 26274727 TI - The authors reply. PMID- 26274728 TI - Ultrasound-Guided Central Venous Catheterization: It Is High Time to Use a Correct Terminology. PMID- 26274729 TI - The authors reply. PMID- 26274730 TI - Neurologically Favorable Outcome Is Still Possible Despite Myoclonus in Comatose Survivors of Cardiac Arrest. PMID- 26274731 TI - The authors reply. PMID- 26274732 TI - Model Calibration in a Large Cohort Study. PMID- 26274733 TI - The authors reply. PMID- 26274734 TI - Early Mobilization in ICU: About New Strategies in Physiotherapy's Care. PMID- 26274735 TI - The Area Under the Concentration-Time Curve Is a Better Estimate for Vancomycin Exposure Than Trough Levels. PMID- 26274736 TI - Triple assessment is not necessary in most young women referred with breast symptoms. AB - INTRODUCTION: A palpable lesion in the breast is usually subjected to triple assessment (clinical examination [CE], imaging and core biopsy [CB] or fine needle aspiration [FNA]) to minimise the risk of missing breast cancer. However, breast cancer is rare in young women, and triple assessment (especially CB) is invasive and expensive. Our aim was to see whether CB/FNA could be avoided in young women with benign findings on CE and imaging. METHODS: This study analysed data from a prospectively entered database on female patients aged under 25 years who attended a rapid diagnosis breast clinic over a 68-month period. RESULTS: Among 10,301 patients seen, 955 females (9.3%) were aged <25 years. The most common presenting complaint was a lump, followed by pain and nipple discharge. CE was normal or revealed benign findings in all except 15 patients, in whom it was indeterminate. Ultrasonography was performed in 692 patients (72%) and was normal (n=289) or benign (n=382) in all except 21 patients, in whom it was indeterminate. In six patients, both were indeterminate. A total of 317 patients (35%) had triple assessment: FNA in 106, CB in 239 and both in 9 cases. No cancers were diagnosed. CONCLUSIONS: It would appear safe to omit FNA/CB in patients aged under 25 years when clinical and ultrasonography findings are normal or benign. This approach would have avoided needle biopsies in all but 30 patients (3%) in the study. PMID- 26274737 TI - Segmental colonic length and mobility. AB - INTRODUCTION: Locoregional variation in the human colon is important in surgical practice; the length and mobility of different colonic regions impacts on laparoscopic and endoscopic colorectal procedures. The aim of this study was to refine anatomical understanding of the colon in terms of segmental length and mobility. METHODS: The colons of 35 cadavers were examined to determine lengths of caecum as well as ascending, transverse, descending and rectosigmoid colon, and to characterise colonic mobility at each location in terms of the mesenteric attachments. The presence of Jackson's membrane (a congenital peritoneal band of the right colon) was also documented. RESULTS: The mean total colonic length was 131.2cm (standard deviation [SD]: 13.4cm). There was no correlation with height, age or sex; the best predictor of total colonic length was the length of the rectosigmoid segment. The mean height of the transverse mesocolon was 7.4cm (SD: 3.6cm) and that of the sigmoid mesocolon was 6.3cm (SD: 2.6cm). Two-thirds of the subjects had a mobile portion of the ascending colon and nearly one-third had a mobile descending colon. A mobile ascending colon was significantly more common in females. Jackson's membrane was present in 66% of the subjects. CONCLUSIONS: This cadaveric study suggests that rectosigmoid length accounts for most of the variability in total colonic length. The significant proportion of colons with mobility of the ascending and descending segments prompts revision of the traditional anatomical teaching of these segments as fixed and retroperitoneal. Mobility of the ascending colon may account for the anecdotal finding that colonoscopy is more challenging in female patients. Jackson's membrane was identified in most colons. PMID- 26274738 TI - Routine versus selective histological examination after cholecystectomy to exclude incidental gallbladder carcinoma. AB - Introduction Gallstone disease is treated commonly with cholecystectomy. Malignant disease of the gallbladder may present similarly and has a poor prognosis. It is common for cholecystectomy specimens to be sent for histological examination to exclude malignancy. However, the incidence of incidental gallbladder carcinoma (IGBC) is low and it has therefore been suggested that macroscopic inspection of the gallbladder by the surgeon, followed by selective histological examination of abnormal specimens, may be safe and cost saving. Methods All cholecystectomies performed between 1 May 2003 and 1 September 2009 were identified from clinical coding. Pathology records were used to identify gallbladder malignancies; these were searched manually to identify IGBC. Pathology reports and case notes were cross-referenced to determine whether there were macroscopic abnormalities present. Annual cost savings were estimated by comparing the number of gallbladder specimens over one year (May 2013 - April 2014) with the total number of cholecystectomies performed in that time. Results Of 4,776 cholecystectomies identified, 12 (0.25%) were cases of IGBC. These cases had a higher median age (68 vs 54 years, p<0.001) and a higher proportion were emergency operations (50% vs 12%, p<0.001). All cases had some form of macroscopic abnormality, most commonly wall thickening (n=6, 50%). Only two cases (17%) had a visible tumour present. Conclusions All cases of IGBC in this study had a macroscopically abnormal gallbladder. Our findings suggest it is safe to adopt a selective approach to histological examination. Savings of almost L20,500 per annum have been achieved. PMID- 26274739 TI - Is there an association between body temperature and serum lactate levels in hip fracture patients? AB - Introduction Hyperlactataemia is associated with adverse outcomes in trauma cases. It is thought to be the result of anaerobic respiration during hypoperfusion. This produces much less energy than complete aerobic glycolysis. Low body temperature in the injured patient carries an equally poor prognosis. Significant amounts of energy are expended in maintaining euthermia. Consequently, there may be a link between lactate levels and dysthermia. Hyperlactataemia may be indicative of inefficient energy production and therefore insufficient energy to maintain euthermia. Alternatively, significant amounts of available oxygen may be sequestered in thermoregulation, resulting in anaerobic respiration and lactate production. Our study investigated whether there is an association between lactate levels and admission body temperature in hip fracture patients. Furthermore, it looked at whether there is a difference in the mean lactate levels between hip fracture patients with low (<36.5 degrees C), normal (36.5-37.5 degrees C) and high (>37.5 degrees C) body temperature on admission, and for patients who have low body temperature, whether there is a progressive rise in serum lactate levels as body temperature falls. Methods The admission temperature and serum lactate of 1,162 patients presenting with hip fracture were recorded. Patients were divided into the euthermic (body temperature 36.5-37.5 degrees C), the pyrexial (>37.5 degrees C) and those with low body temperature (<36.5 degrees C). Admission lactate and body temperature were compared. Results There was a significant difference in age between the three body temperature groups (p=0.007). The pyrexial cohort was younger than the low body temperature group (mean: 78 vs 82 years). Those with low body temperature had a higher mean lactate level than the euthermic (2.2mmol/l vs 2.0mmol/l, p=0.03). However, there was no progressive rise in serum lactate level as admission temperature fell. Conclusions The findings suggest that in hip fracture patients, the body attempts initially to maintain euthermia, incurring an oxygen debt. This would explain the difference in lactate level between the low body temperature and euthermic cohorts. The fact that there is no correlation with the degree of temperature depression and lactate levels indicates that the body does not fuel thermohomeostasis indefinitely with oxygen. Instead, in part, it abandons thermoregulatory mechanisms. Consequently, in this population, active rewarming may be indicated rather than depending on patients' own thermogenic ability. PMID- 26274740 TI - The impact of a dedicated orthoplastic operating list on time to soft tissue coverage of open lower limb fractures. AB - An observational study was conducted of 105 patients presenting with an open fracture of the tibia or ankle to determine the impact of a dedicated orthoplastic operating list on our management of these injuries over the time period January 2012 to July 2014. There were 51 patients before and 54 after the introduction of the orthoplastic list. Significant improvements were noted in our ability to deliver a service in line with national guidelines across all Gustilo Anderson grades of injury. Among patients with the most severe grades of injury (Gustilo types IIIB and IIIC), there was a trend towards an improved time to first skeletal stabilisation (29.5 vs 14.2 hours, p=0.068), an improvement in time to soft tissue coverage (173.6 vs 88.1 hours, p=0.009) and a trend towards a reduced length of inpatient stay (32.6 vs 23.2 days, p=0.138). Where the 72-hour target had been breached, there was a significant improvement in the proportion of patients covered within 7 days of injury (48.2% vs 83.3%, p=0.017). Our compliance with national management standards increased significantly to reflect these improvements in care. These results support the implementation of dedicated orthoplastic operating sessions to meet the growing burden of patients presenting with open fractures at specialist centres. PMID- 26274741 TI - Is abdominal tuberculosis a surgical problem? AB - INTRODUCTION: Abdominal tuberculosis (TB) has always been a diagnostic challenge, even for the astute surgeon. In developing countries, extrapulmonary TB often presents as an acute abdomen in surgical emergencies such as perforations and obstructions of the gut. Abdominal TB in different forms has been found more often as an aetiology for the chronic abdomen. This paper aims to evaluate TB as a surgical problem. METHODS: A comprehensive review of the literature on abdominal TB was undertaken. PubMed searches for articles listing abdominal TB/different types/diagnosis/treatment (1980-2012) were performed. RESULTS: TB is still a global health problem and the abdomen is one of the most common sites of extrapulmonary TB. Presentation may vary from an acute abdomen to a number of different chronic presentations, which can mimic other abdominal diseases. While some may benefit from antitubercular therapy, others may develop surgical problems such as strictures or obstruction, which may necessitate surgical intervention. CONCLUSIONS: Abdominal TB should always be considered one of the differential diagnoses of acute or chronic abdomen in endemic areas. PMID- 26274742 TI - From guidelines to standards of care for open tibial fractures. AB - INTRODUCTION: The standards for the management of open fractures of the lower limb published by the British Association of Plastic, Reconstructive and Aesthetic surgeons (BAPRAS) and British Orthopaedic Association (BOA) were introduced to improve the treatment received by patients after open injury to the lower limb. These Standards were released after BAPRAS/BOA published Guidelines for the management of open tibial fractures. METHODS: We wished to determine the impact of these Standards upon the surgical management of open tibial fractures by comparing patients admitted to an orthoplastic centre in the 45 months concluding December 2009 (the Guidelines era) with those admitted during 2011 (the Standards era). Surgical procedures required during the first 30 days and 12 months after injury were determined. Cases were divided into 'directly admitted patients' (DAP) and 'transferred patients' (TP). Standards-era patients were divided further into those who had surgery exclusively at the orthoplastic centre (orthoplastic patients (OPP)) and those transferred after surgery (TASP). RESULTS: The number of TP trebled in frequency in the Standards era, 25% of whom were transferred before surgery. Significantly fewer surgical procedures were required for DAP and OPP groups compared with TP (and TASP) groups in both eras (Mann-Whitney U-test, p=0.05). DAP and OPP groups during the Standards era underwent the fewest procedures, with the vast majority of cases treated with two or fewer procedures in the first 12 months (88% and 80%, respectively, compared with 61% in the Guidelines era). In the Guidelines era, 44% of TP cases and in the Standards era 39% of TP and 29% of TASP groups underwent two or fewer procedures. Approximately two-thirds of open tibial fractures managed in our orthoplastic centre were patients transferred after surgery. The greatest impact of the Standards was evident for those who underwent surgery exclusively in the orthoplastic centre, reflecting a more deliberate combined strategy. CONCLUSION: These findings vindicate the Standards as well as mandating reorganisation and resourcing of orthoplastic services to ensure immediate transfer and early combined surgery. By increasing the capacity to deal with time-dependent initial surgery, the surgical burden that the patient must endure, and which the service must provide, are reduced. PMID- 26274746 TI - Management of adult spontaneous spondylodiscitis and its rising incidence. AB - INTRODUCTION: Spondylodiscitis refers to the infection of the intervertebral disc and osteomyelitis of the adjacent endplates, and it is uncommon in the developed world. Broad consensus indicates its incidence is on the rise. METHODS: The aim of this retrospective study was twofold. First, we sought to give an up-to-date incidence estimate by comparing case presentation over two time periods (1995 1999 and 2008-2011). Data from the England and Wales census in 2001 and 2011 were used for incidence estimation. The second part of this study aimed to generate management guidance from data from medical and radiographic records of the 2008 2011 patient cohort. RESULTS: The incidence of adult spontaneous spondylodiscitis in the local region between 2008 and 2011 was 3.67/100,000 per year, representing a 150% increase from the incidence in 1995-1999. Our data demonstrate that methicillin sensitive Staphylococcus aureus remains the most common offending pathogen of spontaneous spondylodiscitis. The mean C-reactive protein (CRP) level remained at >30mg/l after a month of starting antibiotic treatment in both medically and surgically managed groups. CONCLUSIONS: Evidence suggests that the incidence of spondylodiscitis is on the rise. A review of our case series has demonstrated the effectiveness of intravenous antibiotic therapy. While no official guidance exists for when to switch from intravenous to oral antibiotics, our study shows that CRP at 1 month is >30mg/l and we recommend 6 weeks of intravenous therapy, followed by 6 further weeks of oral therapy. PMID- 26274747 TI - The role of WNT signalling in urothelial cell carcinoma. AB - Urothelial cell carcinoma (UCC) of the bladder is one of the most common malignancies, causing considerable morbidity and mortality worldwide. It is unique among the epithelial carcinomas as two distinct pathways to tumourigenesis appear to exist: low grade, recurring papillary tumours usually contain oncogenic mutations in FGFR3 or HRAS whereas high grade, muscle invasive tumours with metastatic potential generally have defects in the pathways controlled by the tumour suppressors p53 and retinoblastoma. Over the last two decades, a number of transgenic mouse models of UCC, containing deletions or mutations of key tumour suppressor genes or oncogenes, have helped us understand the mechanisms behind tumour development. In this summary, I present my work investigating the role of the WNT signalling cascade in UCC. PMID- 26274752 TI - Meta-analysis of elective surgical complications related to defunctioning loop ileostomy compared with loop colostomy after low anterior resection for rectal carcinoma. AB - Introduction Defunctioning loop ileostomy (LI) and loop colostomy (LC) are used widely to protect/treat anastomotic leakage after colorectal surgery. However, it is not known which surgical approach has a lower prevalence of surgical complications after low anterior resection for rectal carcinoma (LARRC). Methods We conducted a literature search of PubMed, MEDLINE, Ovid, Embase and Cochrane databases to identify studies published between 1966 and 2013 focusing on elective surgical complications related to defunctioning LI and LC undertaken to protect a distal rectal anastomosis after LARRC. Results Five studies (two randomized controlled trials, one prospective non-randomized trial, and two retrospective trials) satisfied the inclusion criteria. Outcomes of 1,025 patients (652 LI and 373 LC) were analyzed. After the construction of a LI or LC, there was a significantly lower prevalence of sepsis (p=0.04), prolapse (p=0.03), and parastomal hernia (p=0.02) in LI patients than in LC patients. Also, the prevalence of overall complications was significantly lower in those who received LIs compared with those who received LCs (p<0.0001). After closure of defunctioning loops, there were significantly fewer wound infections (p=0.006) and incisional hernias (p=0.007) in LI patients than in LC patients, but there was no significant difference between the two groups in terms of overall complications. Conclusions The results of this meta-analysis show that a defunctioning LI may be superior to LC with respect to a lower prevalence of surgical complications after LARRC. PMID- 26274753 TI - Evaluating the British sarcoma referral form. AB - INTRODUCTION: This study investigated the accuracy of general practitioner (GP) referrals under the two-week wait pathway for soft tissue sarcomas and whether the current National Institute for Health and Care Excellence criteria should be refined. METHODS: All patients referred under the two-week wait system to one centre over the course of one year were reviewed. Comparison was made between the criteria identified by the GP and those confirmed by the centre to assess the accuracy of the referrals, and to identify what criteria predicted malignancy. RESULTS: Overall, 135 patients were referred to our unit with a mean age of 56.4 years. Of these, 45 (33%) were found to have a malignant tumour. Factors identified by the GP were accurate in 74% of cases. The best predictor of malignancy was 'size >5cm' (76% sensitivity) while 'pain' was the least useful (27% sensitivity). Lowering the threshold for concern to a size of >4cm increased sensitivity to 89%. Although 106 patients had undergone some form of imaging prior to referral, this did not increase the likelihood of malignancy being detected. The combination of factors most likely to predict malignancy was a size of >5cm, increase in size, deep location and no pain (10 out of 13 referrals, 77% accuracy). CONCLUSIONS: Based on the results of this study, we recommend an adaption of the existing features for concern. The new feature for concern should be 'size >4cm' and the factor 'pain' should be removed from the urgent referral form. PMID- 26274754 TI - A prospective cohort study of risk prediction in simultaneous pancreas and kidney transplantation. AB - INTRODUCTION: Current risk prediction scoring systems in pancreas transplantation are limited to organ factors and are specific to predicting graft outcome. They do not consider recipient factors or inform regarding recipient morbidity. The aim of this study was to assess the utility of commonly used general surgical risk prediction models (P-POSSUM [Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity], MODS [multiple organ dysfunction score], Charlson co-morbidity index, revised cardiac risk index, ASA [American Society of Anesthesiologists] grade and Waterlow score), and to correlate them with total length of hospital stay (LOS) and critical care unit (CCU) LOS, important surrogate markers of patient outcome. METHODS: All risk prediction scores were calculated prospectively for all simultaneous pancreas and kidney (SPK) transplant recipients from November 2011 to October 2013, and correlated with outcome measures. RESULTS: Overall, 57 SPK transplant recipients were analysed. The mean age was 42.0 years (standard deviation [SD]: 7.60 years), 27 (52%) were male and the mean body mass index was 25.43kg/m(2) (SD: 3.11kg/m(2)). The mean pancreas and kidney cold ischaemic times were 703 minutes (SD: 182 minutes) and 850 minutes (SD: 192 minutes) respectively. The median total LOS and mean CCU LOS was 17 days (range: 8-79 days) and 7 days (SD: 4.04 days) respectively. When correlated with risk prediction scores, Waterlow score was the only significant predictor of total LOS and CCU LOS (p<0.001 [Spearman's correlation] and p=0.001 [Pearson's correlation] respectively). CONCLUSIONS: Preoperative risk prediction plays an important part in planning perioperative care. To date, no validated risk prediction scoring system exists for SPK transplantation. This prospective study indicates that Waterlow score identifies high risk individuals and has value in the prediction of outcome following SPK transplantation. PMID- 26274755 TI - Ultrasonography alone can reliably locate parathyroid tumours and facilitates minimally invasive parathyroidectomy. AB - INTRODUCTION: Minimally invasive parathyroidectomy (MIP) is performed via a short incision (<=3cm). Previous studies have employed multiple imaging modalities including ultrasonography, sestamibi imaging and/or intraoperative parathyroid hormone assay. We present our eight-year experience of MIP using ultrasonography alone. METHODS: One hundred parathyroidectomies performed by a single surgeon between April 2004 and December 2012 were identified in a prospectively maintained database. All patients underwent ultrasonography including preoperative marking of the lesion by a single radiologist. No other localising diagnostic tests were performed. RESULTS: Of the 100 patients (69% female) who underwent parathyroidectomy, 93 had MIP. The median age of all cases was 58 years (range: 19-90 years). All patients exhibited an elevated parathyroid hormone level (median: 19pmol) in the presence of hypercalcaemia (median: 2.86mmol/l, range: 2.54-3.94mmol/l). Conventional surgery was indicated in seven patients owing to the need for concurrent thyroidectomy. The median operative time was 30 minutes (range: 10-130 minutes). Ultrasonography localised parathyroid tumour position correctly in 98% of patients who underwent MIP, and in 97% across both MIP and non-MIP groups. Postoperative complications requiring treatment included pancreatitis and symptomatic hypocalcaemia. Follow-up review at 6-8 weeks demonstrated that 86% of open cases (6/7) and 94% of MIP cases (87/93) were rendered normocalcaemic. CONCLUSIONS: Our study is the first to demonstrate that the sole use of ultrasonography including preoperative marking can localise parathyroid tumours correctly in 98% of cases suitable for MIP. PMID- 26274756 TI - One-year mortality in patients with bone and soft tissue sarcomas as an indicator of delay in presentation. AB - INTRODUCTION: For many cancers, one-year mortality following diagnosis is a reflection of either advanced stage at diagnosis, multiple co-morbidities and/or complications of treatment. One-year mortality has not been reported for soft tissue or bone sarcomas. This study reports 1-year sarcoma mortality data over a 25-year period, investigates prognostic factors and considers whether a delay in presentation affects 1-year mortality. METHODS: A total of 4,945 newly diagnosed bone sarcoma and soft tissue sarcoma patients were identified from a prospectively maintained, single institution oncology database. Of these, 595 (12%) died within 1 year of diagnosis. Both patient factors and tumour characteristics available at diagnosis were analysed for effect. RESULTS: There was significant variation in one-year mortality between different histological subtypes. There has been no significant change in mortality rate during the last 25 years (mean: 11.7%, standard deviation: 2.8 percentage points). Soft tissue sarcoma patients who survived over one year reported a longer duration of symptoms preceding diagnosis than those who died (median: 26 vs 20 weeks, p<0.001). Prognostic factors identified in both bone and soft tissue sarcomas mirrored those for mid to long-term survival, with high tumour stage, large tumour size, metastases at diagnosis and increasing age having the greatest predictive effect. CONCLUSIONS: One-year mortality in bone and soft tissue sarcoma patients is easy to measure, and could be a proxy for late presentation and therefore a potential performance indicator, similar to other cancers. It is possible to predict the risk of one-year mortality using factors available at diagnosis. Death within one year does not correlate with a long history but is associated with advanced disease at diagnosis. PMID- 26274757 TI - Distal tibial fractures are a poorly recognised complication with fibula free flaps. AB - The fibula free flap is ideal for complex jaw reconstructions, with low reported donor and flap morbidity. We discuss a distal tibial stress fracture two months following a vascularised fibula free flap procedure. Despite being an unrecognised complication, a literature review produced 13 previous cases; only two were reported in the reconstructive surgery literature, with the most recent claiming to be the first. The majority of these studies treated this fracture non operatively; none reported their patient follow-up. Each case presented with ipsilateral leg pain, which has been cited as an early donor site morbidity in as many as 40% of fibula free flap cases. It is known that the fibula absorbs at least 15% of leg load on weight bearing. Studies have shown severe valgus deformities in up to 25% of patients with fibulectomies. We treated our patient operatively, first correcting his worsening valgus deformity with an external fixator, then reinforcing his healed fracture with a long distal tibial plate. We believe that this complication is underreported, unexpected and not mentioned during the consenting process. By highlighting the management of our case and the literature, we aim to increase awareness (and thus further reporting and appropriate management) of this debilitating complication. PMID- 26274758 TI - Parastomal evisceration as an extremely rare complication of a common procedure. AB - The creation of an abdominal stoma is a common procedure performed as part of the treatment for many conditions. Common complications include poor stoma siting, high output, skin irritation, ischaemia, retraction, parastomal hernia and prolapse. An extremely rare stoma complication is parastomal evisceration. We present a case of a 48-year-old woman who presented to us with parastomal evisceration as a late complication of a transverse colostomy. It is the second case reported as a complication of this procedure but the first that occurred after such a long postoperative period (almost 18 months). PMID- 26274759 TI - Giant haemangioma of the liver with haemangiodudenal fistula: the first reported case in literature. AB - Giant liver haemangiomas are usually asymptomatic with normal liver function, which makes the course long and uneventful. The most commonly reported complications of giant haemangiomas are rupture with intraperitoneal haemorrhage that is either traumatic or non-traumatic, consumption coagulopathy, Budd-Chiari syndrome and congestive heart failure. We describe the first reported complications of a giant liver haemangioma as a fistula between the haemangioma and the gastrointestinal tract. PMID- 26274760 TI - Small bowel obstruction via herniation through an iatrogenic defect of the falciform ligament following laparoscopic cholecystectomy. AB - Internal herniation of the small bowel through a defect in the falciform ligament and subsequent small bowel obstruction is exceedingly rare with the majority of previous cases being attributed to congenital abnormalities. As laparoscopic techniques approach the forefront of modern surgery, an iatrogenic source for a falciform ligament defect has emerged over the last decade. In this case, a 50 year-old patient presented with signs of acute small bowel obstruction 10 days after a laparoscopic cholecystectomy. On diagnostic laparoscopy, part of the jejunum was found to have herniated through an opening in the falciform ligament. This was likely to have been caused by trauma during the cholecystectomy. Following relief of the obstruction, the defect was closed with polyglactin sutures. PMID- 26274761 TI - Delayed laparoscopic mesh infection presenting as an abdominal mass. AB - A 56-year-old man presented with a delayed mesh infection 8 years following an elective laparoscopic totally extraperitoneal (TEP) bilateral hernia repair. Sterile pus was drained percutaneously as a temporising measure prior to removal of the right-hand mesh; the left-sided mesh was adherent to the femoral vessels and minimally contaminated. Delayed mesh infection is a rare occurrence. This case is the fourth example and the longest following initial operation. Removal of the infected mesh is advocated. PMID- 26274762 TI - Presentation and treatment of anterior cervical hyperostosis. AB - We report a case of severe anterior cervical hyperostosis presenting with dysphagia. PMID- 26274763 TI - Tracheo-oesophageal fistula in a patient with chronic sarcoidosis. AB - Sarcoidosis is a common multisystem granulomatous condition of unknown aetiology, predominantly involving the respiratory system. Tracheal stenosis has been described but we believe that we present the first case of a tracheo-oesophageal fistula secondary to chronic sarcoidosis. A 57-year-old woman with sarcoidosis, a known tracheal stricture and a Polyflex((r)) stent in situ presented with stridor. Bronchoscopy confirmed in-stent stenosis, by exuberant granulation tissue. The stent was removed and the granulation tissue was resected accordingly. Postoperatively, the patient was noticed to have an incessant cough and video fluoroscopy raised the suspicion of a tracheo-oesophageal fistula. A repeat bronchoscopy demonstrated marked granulation tissue, accompanied by a fistulous connection with the oesophagus at the mid-lower [middle of the lower] third of the trachea. Three Polyflex((r)) stents were sited across the entire length of the trachea. Sarcoidosis presents with varying clinical manifestations and disease progression. Tracheal involvement appears to be a rare phenomenon and usually results in stenosis. To date, there has been little or no documented literature describing the formation of a tracheo-oesophageal fistula resulting from sarcoidosis. Early reports documented the presence of sarcoidosis induced weakening in the tracheal wall, a process termed tracheal dystonia. Weaknesses are more apparent in the membranous aspect of the trachea. Despite the rare nature of such pathology, this case report highlights the need to consider the presence of a tracheo-oesophageal fistula in sarcoidosis patients presenting with repeat aspiration in the absence of an alternate pathology. PMID- 26274764 TI - Fabrication of flexible and self-standing inorganic-organic three phase magneto dielectric PVDF based multiferroic nanocomposite films through a small loading of graphene oxide (GO) and Fe3O4 nanoparticles. AB - Flexible inorganic-organic magneto-electric (ME) nanocomposite films (PVDF, PVDF GO, PVDF-Fe3O4 and PVDF-GO-Fe3O4), composed of well-dispersed graphene oxide (GO 5 wt%) and magnetic Fe3O4 nanoparticles (5 wt%) embedded into a poly(vinylidene fluoride) (PVDF) matrix, have been prepared by a solvent casting route. The magnetic, ferroelectric, dielectric, magneto-dielectric (MD) coupling and structural properties of these films have been systematically investigated. Magnetic (Ms = 2.21 emu g(-1)) and ferroelectric (P = 0.065 MUC cm(-2)) composite films of PVDF-GO-Fe3O4 (PVDF loaded with 5% GO and 5% Fe3O4) with an MD coupling of 0.02% at room temperature (RT) showed a three times higher dielectric constant than that of the pure PVDF film, with a dielectric loss as low as 0.6. However, the PVDF-Fe3O4 film, which exhibited improved magnetic (Ms = 2.5 emu g(-1)) and MD coupling (0.04%) properties at RT with a lower dielectric loss (0.3), exhibited decreased ferroelectric properties (P = 0.06 MUC cm(-2)) and dielectric constant compared to the PVDF-GO-Fe3O4 film. MD coupling measurements carried out as a function of temperature on the multi-functional PVDF-GO-Fe3O4 film showed a systematic increase in MD values up to 100 K and a decrease thereafter. The observed magnetic, ferroelectric, dielectric, MD coupling and structural properties of the nanocomposite films are attributed to the homogeneous dispersion and good alignment of Fe3O4 nanoparticles and GO in the PVDF matrix along with a partial conversion of nonpolar alpha-phase PVDF to polar beta-phase. The above multi-functionality of the composite films of PVDF-Fe3O4 and PVDF-GO Fe3O4 paves the way for their application in smart multiferroic devices. PMID- 26274765 TI - A Cost-effective and Reliable Method to Predict Mechanical Stress in Single-use and Standard Pumps. AB - Pumps are mainly used when transferring sterile culture broths in biopharmaceutical and biotechnological production processes. However, during the pumping process shear forces occur which can lead to qualitative and/or quantitative product loss. To calculate the mechanical stress with limited experimental expense, an oil-water emulsion system was used, whose suitability was demonstrated for drop size detections in bioreactors(1). As drop breakup of the oil-water emulsion system is a function of mechanical stress, drop sizes need to be counted over the experimental time of shear stress investigations. In previous studies, the inline endoscopy has been shown to be an accurate and reliable measurement technique for drop size detections in liquid/liquid dispersions. The aim of this protocol is to show the suitability of the inline endoscopy technique for drop size measurements in pumping processes. In order to express the drop size, the Sauter mean diameter d32 was used as the representative diameter of drops in the oil-water emulsion. The results showed low variation in the Sauter mean diameters, which were quantified by standard deviations of below 15%, indicating the reliability of the measurement technique. PMID- 26274770 TI - Unconventional Ventilation: High Frequency Oscillatory Ventilation & Adaptive Support Ventilation. PMID- 26274771 TI - Gait analysis parameters of healthy human subjects with asymmetric loads. AB - This article focuses on the analysis of gait parameters, ground reaction forces (GRF), and motion signals, for the various asymmetric loads carried by healthy human subjects during walking. Eight asymptomatic human volunteers were enrolled in this study. They were asked to walk, at self-selected pace, with various weights ranging from 0 to 11.33 kg (25 lbs) in 2.26 kg (5 lbs) increments, in one hand on a wooden area equipped with a force platform. Moreover, motion data were recorded from lumbar L1 vertebrae at a frequency of 120 Hz. Three trials of data have been recorded for each subject. In order to quantify the effect of increasing loads on the GRF we define the compression area, restitution area, and coefficient of restitution (COR) for GRF curves. We observe an increase in the compression area with respect to the load and almost constant values for the COR. For motion signals analysis we employ wavelet theory. The signals obtained from the lumbar L1 sensor of the spine vertebrae show a decrease in the wavelet detail energy, for the levels 3, 4, and 5, with respect to increasing loads. PMID- 26274772 TI - Photothrombosis-induced Focal Ischemia as a Model of Spinal Cord Injury in Mice. AB - Spinal cord injury (SCI) is a devastating clinical condition causing permanent changes in sensorimotor and autonomic functions of the spinal cord (SC) below the site of injury. The secondary ischemia that develops following the initial mechanical insult is a serious complication of the SCI and severely impairs the function and viability of surviving neuronal and non-neuronal cells in the SC. In addition, ischemia is also responsible for the growth of lesion during chronic phase of injury and interferes with the cellular repair and healing processes. Thus there is a need to develop a spinal cord ischemia model for studying the mechanisms of ischemia-induced pathology. Focal ischemia induced by photothrombosis (PT) is a minimally invasive and very well established procedure used to investigate the pathology of ischemia-induced cell death in the brain. Here, we describe the use of PT to induce an ischemic lesion in the spinal cord of mice. Following retro-orbital sinus injection of Rose Bengal, the posterior spinal vein and other capillaries on the dorsal surface of SC were irradiated with a green light resulting in the formation of a thrombus and thus ischemia in the affected region. Results from histology and immunochemistry studies show that PT-induced ischemia caused spinal cord infarction, loss of neurons and reactive gliosis. Using this technique a highly reproducible and relatively easy model of SCI in mice can be achieved that would serve the purpose of scientific investigations into the mechanisms of ischemia induced cell death as well as the efficacy of neuroprotective drugs. This model will also allow exploration of the pathological changes that occur following SCI in live mice like axonal degeneration and regeneration, neuronal and astrocytic Ca(2+) signaling using two photon microscopy. PMID- 26274773 TI - Generation of Scalable, Metallic High-Aspect Ratio Nanocomposites in a Biological Liquid Medium. AB - The goal of this protocol is to describe the synthesis of two novel biocomposites with high-aspect ratio structures. The biocomposites consist of copper and cystine, with either copper nanoparticles (CNPs) or copper sulfate contributing the metallic component. Synthesis is carried out in liquid under biological conditions (37 degrees C) and the self-assembled composites form after 24 hr. Once formed, these composites are highly stable in both liquid media and in a dried form. The composites scale from the nano- to micro- range in length, and from a few microns to 25 nm in diameter. Field emission scanning electron microscopy with energy dispersive X-ray spectroscopy (EDX) demonstrated that sulfur was present in the NP-derived linear structures, while it was absent from the starting CNP material, thus confirming cystine as the source of sulfur in the final nanocomposites. During synthesis of these linear nano- and micro composites, a diverse range of lengths of structures is formed in the synthesis vessel. Sonication of the liquid mixture after synthesis was demonstrated to assist in controlling average size of the structures by diminishing the average length with increased time of sonication. Since the formed structures are highly stable, do not agglomerate, and are formed in liquid phase, centrifugation may also be used to assist in concentrating and segregating formed composites. PMID- 26274774 TI - [The Compression Syndrome of Lumbar Arteries - Case Report of a Rare Disease Pattern]. AB - STUDY DESIGN: We present a monocentric analysis of the lumbar artery compression syndrome (LACS) in the form of a case report. OBJECTIVES: Literature information was collected about the symptoms, diagnosis and treatment of this rare disorder in the context of the existing data. METHODS: The current medical literature includes only one report about three cases of LACS, collected over 20 years in France and Germany. We compared these cases with the experience of the European Vascular Center Aachen-Maastricht. RESULTS: The symptoms of this rare disorder are dominated by reversible, motion-dependent paralysis of the legs. Compression of the right lumbar arteries by muscular fibres or connective tissue is a fundamental cause. CONCLUSION: Surgical treatment, which means decompression of the lumbar arteries via a thoracolaparotomy, is an appropriate therapy with few complications and good long-term results. PMID- 26274775 TI - Assessment of Endothelial Cell Migration After Exposure to Toxic Chemicals. AB - Exposure to chemical substances (including alkylating chemical warfare agents like sulfur and nitrogen mustards) cause a plethora of clinical symptoms including wound healing disorder. The physiological process of wound healing is highly complex. The formation of granulation tissue is a key step in this process resulting in a preliminary wound closure and providing a network of new capillary blood vessels - either through vasculogenesis (novel formation) or angiogenesis (sprouting of existing vessels). Both vasculo- and angiogenesis require functional, directed migration of endothelial cells. Thus, investigation of early endothelial cell (EEC) migration is important to understand the pathophysiology of chemical induced wound healing disorders and to potentially identify novel strategies for therapeutic intervention. We assessed impaired wound healing after alkylating agent exposure and tested potential candidate compounds for treatment. We used a set of techniques outlined in this protocol. A modified Boyden chamber to quantitatively investigate chemokinesis of EEC is described. Moreover, the use of the wound healing assay in combination with track analysis to qualitatively assess migration is illustrated. Finally, we demonstrate the use of the fluorescent dye TMRM for the investigation of mitochondrial membrane potential to identify underlying mechanisms of disturbed cell migration. The following protocol describes basic techniques that have been adapted for the investigation of EEC. PMID- 26274776 TI - Change isn't always better. AB - Maintaining the identity of acinar cells in the pancreas could help to prevent the development of pancreatic cancer. PMID- 26274778 TI - Quantification of Cytosolic vs. Vacuolar Salmonella in Primary Macrophages by Differential Permeabilization. AB - Intracellular bacterial pathogens can replicate in the cytosol or in specialized pathogen-containing vacuoles (PCVs). To reach the cytosol, bacteria like Shigella flexneri and Francisella novicida need to induce the rupture of the phagosome. In contrast, Salmonella typhimurium replicates in a vacuolar compartment, known as Salmonella-containing vacuole (SCV). However certain mutants of Salmonella fail to maintain SCV integrity and are thus released into the cytosol. The percentage of cytosolic vs. vacuolar bacteria on the level of single bacteria can be measured by differential permeabilization, also known as phagosome-protection assay. The approach makes use of the property of detergent digitonin to selectively bind cholesterol. Since the plasma membrane contains more cholesterol than other cellular membranes, digitonin can be used to selectively permeabilize the plasma membrane while leaving intracellular membranes intact. In brief, following infection with the pathogen expressing a fluorescent marker protein (e.g. mCherry among others), the plasma membrane of host cells is permeabilized with a short incubation in digitonin containing buffer. Cells are then washed and incubated with a primary antibody (coupled to a fluorophore of choice) directed against the bacterium of choice (e.g. anti-Salmonella-FITC) and washed again. If unmarked bacteria are used, an additional step can be done, in which all membranes are permeabilized and all bacteria stained with a corresponding antibody. Following the staining, the percentage of vacuolar and cytosolic bacteria can be quantified by FACS or microscopy by counting single or double positive events. Here we provide experimental details for use of this technique with the bacterium Salmonella typhimurium. The advantage of this assay is that, in contrast to other assay, it provides a quantification on the level of single bacteria, and if analyzed by microscopy provides the exact number of cytosolic and vacuolar bacteria in a given cell. PMID- 26274780 TI - Combined molecular dynamics and continuum solvent approaches (MM-PBSA/GBSA) to predict noscapinoid binding to gamma-tubulin dimer. AB - gamma-tubulin plays crucial role in the nucleation and organization of microtubules during cell division. Recent studies have also indicated its role in the regulation of microtubule dynamics at the plus end of the microtubules. Moreover, gamma-tubulin has been found to be over-expressed in many cancer types, such as carcinomas of the breast and glioblastoma multiforme. These studies have led to immense interest in the identification of chemical leads that might interact with gamma-tubulin and disrupt its function in order to explore gamma tubulin as potential chemotherapeutic target. Recently a colchicine-interacting cavity was identified at the interface of gamma-tubulin dimer that might also interact with other similar compounds. In the same direction we theoretically investigated binding of a class of compounds, noscapinoids (noscapine and its derivatives) at the interface of the gamma-tubulin dimer. Molecular interaction of noscapine and two of its derivatives, amino-noscapine and bromo-noscapine, was investigated by molecular docking, molecular dynamics simulation and binding free energy calculation. All noscapinoids displayed stable interaction throughout simulation of 25 ns. The predictive binding free energy (DeltaGbind) indicates that noscapinoids bind strongly with the gamma-tubulin dimer. However, bromo noscapine showed the best binding affinity (DeltaGbind = -37.6 kcal/mol) followed by noscapine (DeltaGbind = -29.85 kcal/mol) and amino-noscapine (DeltaGbind = 23.99 kcal/mol) using the MM-PBSA method. Similarly using the MM-GBSA method, bromo-noscapine showed highest binding affinity (DeltaGbind = -43.64 kcal/mol) followed by amino-noscapine (DeltaGbind = -37.56 kcal/mol) and noscapine (DeltaGbind = -34.57 kcal/mol). The results thus generate compelling evidence that these noscapinoids may hold great potential for preclinical and clinical evaluation. PMID- 26274779 TI - Long-term Continuous EEG Monitoring in Small Rodent Models of Human Disease Using the Epoch Wireless Transmitter System. AB - Many progressive neurologic diseases in humans, such as epilepsy, require pre clinical animal models that slowly develop the disease in order to test interventions at various stages of the disease process. These animal models are particularly difficult to implement in immature rodents, a classic model organism for laboratory study of these disorders. Recording continuous EEG in young animal models of seizures and other neurological disorders presents a technical challenge due to the small physical size of young rodents and their dependence on the dam prior to weaning. Therefore, there is not only a clear need for improving pre-clinical research that will better identify those therapies suitable for translation to the clinic but also a need for new devices capable of recording continuous EEG in immature rodents. Here, we describe the technology behind and demonstrate the use of a novel miniature telemetry system, specifically engineered for use in immature rats or mice, which is also effective for use in adult animals. PMID- 26274777 TI - A high affinity RIM-binding protein/Aplip1 interaction prevents the formation of ectopic axonal active zones. AB - Synaptic vesicles (SVs) fuse at active zones (AZs) covered by a protein scaffold, at Drosophila synapses comprised of ELKS family member Bruchpilot (BRP) and RIM binding protein (RBP). We here demonstrate axonal co-transport of BRP and RBP using intravital live imaging, with both proteins co-accumulating in axonal aggregates of several transport mutants. RBP, via its C-terminal Src-homology 3 (SH3) domains, binds Aplip1/JIP1, a transport adaptor involved in kinesin dependent SV transport. We show in atomic detail that RBP C-terminal SH3 domains bind a proline-rich (PxxP) motif of Aplip1/JIP1 with submicromolar affinity. Pointmutating this PxxP motif provoked formation of ectopic AZ-like structures at axonal membranes. Direct interactions between AZ proteins and transport adaptors seem to provide complex avidity and shield synaptic interaction surfaces of pre assembled scaffold protein transport complexes, thus, favouring physiological synaptic AZ assembly over premature assembly at axonal membranes. PMID- 26274781 TI - Acid-Triggered Colorimetric Hydrophobic Benzyl Alcohols for Soluble Tag-Assisted Liquid-Phase Synthesis. AB - Simple screening of acid-triggered reactions of methoxybenzyl alcohols led to the development of a novel colorimetric hydrophobic benzyl alcohol (HBA) tag. HBA tag 3 (14) retained high solubility in less polar solvents and excellent precipitation properties in polar solvents. Our routine procedure for tag assisted liquid phase peptide synthesis was applied using HBA tag-3 (14), and an effective synthesis of beta-sheet breaker peptide iAbeta5 (4) was achieved. The tagged peptides showed a vivid blue color under acidic conditions both on TLC plates and in solution, enabling quantitative assay. PMID- 26274782 TI - Cu-Catalyzed Cyanation of Indoles with Acetonitrile as a Cyano Source. AB - Cu-catalyzed cyanation of indoles with acetonitrile for the synthesis of 3 cyanoindoles has been developed. The Cu/TEMPO/(Me3Si)2 system has been identified to promote highly efficient and selective C-H cyanation of indoles by use of unactivated acetonitrile as a cyano source via a sequential iodination/cyanation process in one pot. This reaction furnishes 3-cyanoindoles in moderate to good yields and tolerates a series of functional groups. Moreover, low-cost copper catalysts and hazardless acetonitrile as a cyano source feature the practicability of this reaction. PMID- 26274783 TI - Ras Transformation Overrides a Proliferation Defect Induced by Tpm3.1 Knockout. AB - Extensive re-organisation of the actin cytoskeleton and changes in the expression of its binding proteins is a characteristic feature of cancer cells. Previously we have shown that the tropomyosin isoform Tpm3.1, an integral component of the actin cytoskeleton in tumor cells, is required for tumor cell survival. Our objective was to determine whether cancer cells devoid of Tpm3.1 would evade the tumorgenic effects induced by H-Ras transformation. The tropomyosin isoform (Tpm) expression profile of a range of cancer cell lines (21) demonstrates that Tpm3.1 is one of the most broadly expressed Tpm isoform. Consequently, the contribution of Tpm3.1 to the transformation process was functionally evaluated. Primary embryonic fibroblasts isolated from wild type (WT) and Tpm3.1 knockout (KO) mice were transduced with retroviral vectors expressing SV40 large T antigen and an oncogenic allele of the H-Ras gene, H-RasV12, to generate immortalized and transformed WT and KO MEFs respectively. We show that Tpm3.1 is required for growth factor-independent proliferation in the SV40 large T antigen immortalized MEFs, but this requirement is overcome by H-Ras transformation. Consistent with those findings, we found that Tpm3.1 was not required for anchorage independent growth or growth of H-Ras-driven tumors in a mouse model. Finally, we show that pERK and Importin 7 protein interactions are significantly decreased in the SV40 large T antigen immortalized KO MEFs but not in the H-Ras transformed KO cells, relative to control MEFs. The data demonstrate that H-Ras transformation overrides a requirement for Tpm3.1 in growth factor-independent proliferation of immortalized MEFs. We propose that in the SV40 large T antigen immortalized MEFs, Tpm3.1 is partly responsible for the efficient interaction between pERK and Imp7 resulting in cell proliferation, but this is overidden by Ras transformation. PMID- 26274785 TI - Training the inspiratory muscles improves running performance when carrying a 25 kg thoracic load in a backpack. AB - Load carriage (LC) exercise in physically demanding occupations is typically characterised by periods of low-intensity steady-state exercise and short duration, high-intensity exercise while carrying an external mass in a backpack; this form of exercise is also known as LC exercise. This induces inspiratory muscle fatigue and reduces whole-body performance. Accordingly we investigated the effect of inspiratory muscle training (IMT, 50% maximal inspiratory muscle pressure (PImax) twice daily for six week) upon running time-trial performance with thoracic LC. Nineteen healthy males formed a pressure threshold IMT (n = 10) or placebo control group (PLA; n = 9) and performed 60 min LC exercise (6.5 km h( 1)) followed by a 2.4 km running time trial (LCTT) either side of a double-blind six week intervention. Prior to the intervention, PImax was reduced relative to baseline, post-LC and post-LCTT in both groups (pooled data: 13 +/- 7% and 16 +/- 8%, respectively, p < .05) and similar changes were observed post-PLA. Post-IMT only, resting PImax increased +31% (p < .05) and relative to pre-IMT was greater post-LC (+19%) and post-LCTT (+18%, p < .05), however, the relative reduction in PImax at each time point was unchanged (13 +/- 11% and 17 +/- 9%, respectively, p > .05). In IMT only, heart rate and perceptual responses were reduced post-LC (p < .05). Time-trial performance was unchanged post-PLA and improved 8 +/- 4% after IMT (p < .05). In summary, when wearing a 25 kg backpack, IMT attenuated the cardiovascular and perceptual responses to steady-state exercise and improved high-intensity time-trial performance which we attribute in part to reduced relative work intensity of the inspiratory muscles due to improved inspiratory muscle strength. These findings have real-world implications for occupational contexts. PMID- 26274786 TI - Sequence-Defined Scaffolding of Peptides on Nucleic Acid Polymers. AB - We have developed a method for the T4 DNA ligase-catalyzed DNA-templated polymerization of 5'-phosphorylated pentanucleotides containing peptide fragments. The polymerization proceeds sequence-specifically to generate DNA scaffolded peptides in excellent yields. The method has been shown to tolerate peptides ranging from two to eight amino acids in length with a wide variety of functionality. We validated the capabilities of this system in a mock selection for the enrichment of a His-tagged DNA-scaffolded peptide phenotype from a library, which exhibited a 190-fold enrichment after one round of selection. This strategy demonstrates a promising new approach to allowing the generation and in vitro selection of high-affinity reagents based upon single-stranded DNA scaffolding of peptide fragments. PMID- 26274784 TI - Naked-eye and near-infrared fluorescence probe for hydrazine and its applications in in vitro and in vivo bioimaging. AB - Hydrazine has been applied diffusely in most of the chemical industry; however, it is a hazardous environmental pollutant and highly toxic to organisms. Selective, rapid, and sensitive detection of hydrazine thus becomes absolutely necessary in both biological and environmental sciences. Accordingly, fluorescence probes for hydrazine have been paid great attention in recent years. Disclosed here is the near-infrared (NIR) fluorescence probe with a turn-on fluorescent probe CyJ based on the structure-emission property relationships of the NIR dyes containing an acetyl group as the recognizing moiety. This new probe not only can be readily prepared, but also shows excellent sensing properties. First and most important of all, CyJ is highly selective for N2H4 over various anions, cations, and other amino compounds and has a low limit of detection (LOD) of hydrazine (5.4 ppb as fluorescence sensor and 6.1 ppb as UV sensor). Besides, CyJ exhibited a dramatic increase in fluorescence at lambdamax = 706 nm in the presence of N2H4, and it offers a rapid, colorimetric and vapor sensing detection process for N2H4 in both aqueous solution and diluted human serum. Furthermore, CyJ has good cell-membrane permeability and low cytotoxicity. In addition, we have successfully applied the CyJ to visualize N2H4 in live mouse and, for the first time, in tissues such as the liver, lung, kidney, heart, and spleen. PMID- 26274788 TI - Application of Time-Dependent Density Functional and Natural Bond Orbital Theories to the UV-vis Absorption Spectra of Some Phenolic Compounds. AB - The UV-vis properties of 22 natural phenolic compounds, comprising anthraquinones, neoflavonoids, and flavonoids were systematically examined. The time-dependent density functional theory (TDDFT) approach in combination with the B3LYP, B3LYP-D2, B3P86, and M06-2X functionals was used to simulate the UV-vis spectra of the investigated compounds. It was shown that all methods exhibit very good (B3LYP slightly better) performance in reproducing the examined UV-vis spectra. However, the shapes of the Kohn-Sham molecular orbitals (MOs) involved in electronic transitions were misleading in constructing the MO correlation diagrams. To provide better understanding of redistribution of electron density upon excitation, the natural bond orbital (NBO) analysis was applied. Bearing in mind the spatial and energetic separations, as well as the character of the pi bonding, lone pair, and pi* antibonding natural localized molecular orbitals (NLMOs), the "NLMO clusters" were constructed. NLMO cluster should be understood as a part of a molecule characterized with distinguished electron density. It was shown that all absorption bands including all electronic transitions need to be inspected to fully understand the UV-vis spectrum of a certain compound, and, thus, to learn more about its UV-vis light absorption. Our investigation showed that the TDDFT and NBO theories are complementary, as the results from the two approaches can be combined to interpret the UV-vis spectra. Agreement between the predictions of the TDDFT approach and those based on the NLMO clusters is excellent in the case of major electronic transitions and long wavelengths. It should be emphasized that the approach for investigation of UV-vis light absorption based on the NLMO clusters is applied for the first time. PMID- 26274787 TI - Oxidative stress in dogs with multicentric lymphoma: Effect of chemotherapy on oxidative and antioxidant biomarkers. AB - INTRODUCTION: Lymphoma is one of the most common types of cancer in dogs, characterized by the proliferation of lymphoid cells. The treatment of this type of cancer is usually based on drugs with high toxicity, which can cause severe side effects. OBJECTIVES: Therefore, the aim of this study was to measure the levels of advanced oxidation protein products (AOPP), thiobarbituric acid reactive substances (TBARS), and ferric reducing antioxidant power (FRAP) in dogs with multicentric lymphoma before and after chemotherapy. METHODS: For this purpose, serum samples of 25 dogs diagnosed with multicentric lymphoma and 15 healthy dogs were used. The animals were exposed to CHOP chemotherapy (cyclophosphamide, vincristine, doxorubicin, and prednisone) and serum samples were collected 5 weeks after treatment. RESULTS: High levels of TBARS, AOPP, and FRAP were observed in sera of dogs with multicentric lymphoma when compared to healthy dogs (P < 0.01), and even higher levels (TBARS and AOPP) were found after chemotherapy i.e. treatment exacerbated the oxidative stress levels. On the other hand, FRAP levels did not differ statistically between animals with lymphoma before and after treatment (P > 0.05). Exacerbated oxidative stress was observed in dogs with multicentric lymphoma Group II (Stage IV-V: involvement of lymph nodes and organs) compared to those in Group I (Stage I-III: only affected lymph nodes) of the disease, as well as the dogs with clinical signs and T immunophenotype. Another important result was observed after chemotherapy, where FRAP levels were higher in dogs that showed complete disease remission compared to animals with progressive disease. CONCLUSIONS: Therefore, dogs with lymphoma showed protein oxidation and lipid peroxidation, as well as increased total antioxidants before and after chemotherapy compared to the control group. PMID- 26274789 TI - Should criteria for inclusion in cancer clinical trials be expanded? PMID- 26274790 TI - How high a bar to change neoadjuvant therapy for triple-negative breast cancer? PMID- 26274791 TI - Comparative costs of advanced proton and photon radiation therapies: lessons from time-driven activity-based costing in head and neck cancer. PMID- 26274792 TI - Costs and mortality of recurrent versus de novo hormone receptor-positive/HER2(-) metastatic breast cancer. AB - AIM: To examine cost and mortality differences in postmenopausal women with HR(+)/HER2(-) advanced breast cancer. METHODS: Using claims data (2007-2013), women with newly diagnosed (de novo) stage IV, or early- or late-recurring metastatic breast cancer were identified. RESULTS: Compared with de novo (n = 121) and late-recurrent (n = 106), early-recurrent (n = 172) patients had significantly higher costs in total and for anticancer systemic agents. Adjusted per patient per month costs for early-recurrent patients were US$13,404, versus US$9955 (de novo) and US$9721 (late-recurrent; p = 0.02). Early-recurrent patients' risk of death was twice that of de novo patients (p = 0.02). CONCLUSION: Compared with new diagnosis or late recurrence, early recurrence of HR+/HER2- metastatic breast cancer was associated with higher mortality and healthcare costs. PMID- 26274793 TI - Real-world effectiveness of everolimus-based therapy versus fulvestrant monotherapy in HR(+)/HER2(-) metastatic breast cancer. AB - AIMS: Assessing real-world effectiveness of everolimus-based therapy (EVE) versus fulvestrant monotherapy (FUL) among postmenopausal women with hormone receptor positive (HR(+))/HER2(-) metastatic breast cancer (mBC) after progression on nonsteroidal aromatase inhibitor (NSAI). DATA & METHODS: Medical charts of community-based patients who received EVE or FUL for mBC after NSAI were examined. Progression-free survival (PFS), time on treatment and time to chemotherapy were compared using Kaplan-Meier curves and Cox proportional hazards models adjusting for line of therapy and patient characteristics. RESULTS & CONCLUSION: 192 patients received EVE and 156 FUL. After adjusting for patient characteristics, EVE was associated with significantly longer PFS than FUL (hazard ratio: 0.71; p = 0.045). EVE was associated with better PFS than FUL among NSAI-refractory postmenopausal HR(+)/HER2(-) mBC patients. PMID- 26274794 TI - Deferasirox therapy is associated with reduced mortality risk in a medicare population with myelodysplastic syndromes. AB - AIMS: Iron overload adversely affects patients with myelodysplastic syndromes (MDS), but benefits of iron chelation therapy have not been clearly demonstrated. We examined the association between deferasirox (DFX) therapy and mortality in transfusion-receiving Medicare patients. PATIENTS & METHODS: MDS patients from 2005 to 2008 were identified using ICD-9 codes from 100% Medicare claims. Patients receiving >=20 blood units were observed until death or end of study. Marginal structural models were used for estimation. RESULTS: 3926 patients (10.1% used DFX) were observed for a mean of 48.8 weeks. Each incremental week of DFX was associated with a significant reduction in mortality risk (hazard ratio [HR]: 0.989; 95% CI: 0.983-0.996; p = 0.001). CONCLUSION: DFX therapy is associated with a reduced mortality risk among older MDS patients who received a minimum transfusion threshold. PMID- 26274795 TI - The role of matching when adjusting for baseline differences in the outcome variable of comparative effectiveness studies. AB - AIM: Evaluate performance of analytical strategies commonly used to adjust for baseline differences in continuous outcome variables for comparative effectiveness studies. PATIENTS & METHODS: Data simulations resembling a comparison of HbA1c values after initiation of antidiabetic treatments adjusting for baseline HbA1c. We evaluated change scores, analyses of covariance including linear, nonlinear with/without robust variance estimations, before and after optimal matching. We also evaluated the impact of measurement error. RESULTS: With increasing HbA1c baseline differences between groups, bias in effect estimates and suboptimal CI coverage probabilities increased in all approaches. These issues were further compounded by measurement error. Matching on baseline HbA1c, substantially mitigated these issues. CONCLUSION: In comparative studies with continuous outcomes, matching on baseline values of the outcome variable improves analytical performance. PMID- 26274796 TI - IMPACCT Kids' Care: a real-world example of stakeholder involvement in comparative effectiveness research. AB - The Patient-Centered Outcomes Research Institute has accelerated conversations about the importance of actively engaging stakeholders in all aspects of comparative effectiveness research (CER). Other scientific disciplines have a history of stakeholder engagement, yet few empirical examples exist of how these stakeholders can inform and enrich CER. Here we present a case study which includes the methods used to engage stakeholders, what we learned from them, and how we incorporated their ideas in a CER project. We selected stakeholders from key groups, built relationships with them and collected their feedback through interviews, observation and ongoing meetings during the four research process phases: proposal development, adapting study methods, understanding the context and information technology tool design and refinement. PMID- 26274797 TI - Using linked electronic data to validate algorithms for health outcomes in administrative databases. AB - The validity of algorithms used to identify health outcomes in claims-based and administrative data is critical to the reliability of findings from observational studies. The traditional approach to algorithm validation, using medical charts, is expensive and time-consuming. An alternative method is to link the claims data to an external, electronic data source that contains information allowing confirmation of the event of interest. In this paper, we describe this external linkage validation method and delineate important considerations to assess the feasibility and appropriateness of validating health outcomes using this approach. This framework can help investigators decide whether to pursue an external linkage validation method for identifying health outcomes in administrative/claims data. PMID- 26274798 TI - Apixaban versus edoxaban for stroke prevention in nonvalvular atrial fibrillation. AB - Oral anticoagulation therapy is the mainstay of stroke prevention in nonvalvular atrial fibrillation patients. Vitamin K antagonists (such as warfarin) have been effective conventional oral anticoagulants for several decades. However, due to their limitations in clinical use, several nonvitamin K antagonist oral anticoagulants (NOACs, including dabigatran, rivaroxaban, apixaban and edoxaban) have been developed. Nonetheless, no head to head trials have been performed to directly compare these NOACs in patient cohorts. In this review article, two direct factor Xa inhibitors, apixaban and edoxaban, are briefly described with focus on their pharmacokinetic and pharmacodynamic profiles, plus drug interactions. Moreover, both efficacy and safety will be discussed based on the available data from the large Phase III clinical trials and indirect comparison studies. PMID- 26274800 TI - Society of Biomolecular Imaging and Informatics special issue. PMID- 26274799 TI - Antiplatelet therapies for secondary stroke prevention: an update on clinical and cost-effectiveness. AB - Stroke exacts a huge toll physically, mentally and economically. Antiplatelet therapy is the cornerstone of secondary stroke prevention, and proven drugs available to successfully realize this therapeutic strategy for the long term include aspirin, dipyridamole plus aspirin and clopidogrel. However, government agencies, corporations, health plans and patients desire more information about the clinical- and cost-effectiveness of these established therapies in real-world settings. This paper provides an update on evidence-based secondary stroke prevention with antiplatelet medications, discusses cost-related issues and offers perspective about the future. PMID- 26274801 TI - Differences in patient and physician assessment of a dynamic patient reported outcome tool for chronic pruritus. AB - BACKGROUND: Chronic pruritus is a subjective symptom, mainly measured through patient reported outcomes. Our aim is to assess two different methods regarding the change of symptoms: a visual dynamic pruritus score (vDPS) documented by patients, and a numerical value (nDPS) documented by physicians. METHODS: Inferential statistics and reliability analyses have been performed on data collected in 2013. RESULTS: Data of 701 patients were analysed (45.6% males, 54.4% females, mean age 60 +/- 16 years). The nDPS showed less extreme and generally lower values than the vDPS. There was a slight concordance between both methods; the highest concordance was seen for no/weak change and very good reduction. CONCLUSION: The difference between patient and physician assessed same score points to an important bias in pruritus assessment which has to be taken into account especially in clinical trials. Though further studies are needed, the patient-based assessment seems to be less biased by a social desirability effect. PMID- 26274802 TI - Mechanism of Ion Permeation in Mammalian Voltage-Gated Sodium Channels. AB - Recent determination of the crystal structures of bacterial voltage-gated sodium (NaV) channels have raised hopes that modeling of the mammalian counterparts could soon be achieved. However, there are substantial differences between the pore domains of the bacterial and mammalian NaV channels, which necessitates careful validation of mammalian homology models constructed from the bacterial NaV structures. Such a validated homology model for the NaV1.4 channel was constructed recently using the extensive mutagenesis data available for binding of MU-conotoxins. Here we use this NaV1.4 model to study the ion permeation mechanism in mammalian NaV channels. Linking of the DEKA residues in the selectivity filter with residues in the neighboring domains is found to be important for keeping the permeation pathway open. Molecular dynamics simulations and potential of mean force calculations reveal that there is a binding site for a Na+ ion just inside the DEKA locus, and 1-2 Na+ ions can occupy the vestibule near the EEDD ring. These sites are separated by a low free energy barrier, suggesting that inward conduction occurs when a Na+ ion in the vestibule goes over the free energy barrier and pushes the Na+ ion in the filter to the intracellular cavity, consistent with the classical knock-on mechanism. The NaV1.4 model also provides a good description of the observed Na+/K+ selectivity. PMID- 26274803 TI - Transcriptome Analysis of Thermal Parthenogenesis of the Domesticated Silkworm. AB - Thermal induction of parthenogenesis (also known as thermal parthenogenesis) in silkworms is an important technique that has been used in artificial insemination, expansion of hybridization, transgenesis and sericultural production; however, the exact mechanisms of this induction remain unclear. This study aimed to investigate the gene expression profile in silkworms undergoing thermal parthenogenesis using RNA-seq analysis. The transcriptome profiles indicated that in non-induced and induced eggs, the numbers of differentially expressed genes (DEGs) for the parthenogenetic line (PL) and amphigenetic line (AL) were 538 and 545, respectively, as determined by fold-change >= 2. Gene ontology (GO) analysis showed that DEGs between two lines were mainly involved in reproduction, formation of chorion, female gamete generation and cell development pathways. Upregulation of many chorion genes in AL suggests that the maturation rate of AL eggs was slower than PL eggs. Some DEGs related to reactive oxygen species removal, DNA repair and heat shock response were differentially expressed between the two lines, such as MPV-17, REV1 and HSP68. These results supported the view that a large fraction of genes are differentially expressed between PL and AL, which offers a new approach to identifying the molecular mechanism of silkworm thermal parthenogenesis. PMID- 26274804 TI - Metabolomics Reveals Metabolically Healthy and Unhealthy Obese Individuals Differ in their Response to a Caloric Challenge. AB - OBJECTIVE: To determine if metabolically healthy obese (MHO) individuals have a different metabolic response to a standardized diet compared to lean healthy (LH) and metabolically unhealthy obese (MUO) individuals. METHODS: Thirty adults (35 70 yrs) were classified as LH, MHO, and MUO according to anthropometric and clinical measurements. Participants consumed a standardized high calorie meal (~1330 kcal). Blood glucose and insulin were measured at fasting, and 15, 30, 60, 90 and 120 min postprandially. Additional blood samples were collected for the targeted analysis of amino acids (AAs) and derivatives, and fatty acids (FAs). RESULTS: The postprandial response (i.e., area under the curve, AUC) for serum glucose and insulin were similar between MHO and LH individuals, and significantly lower than MUO individuals (p < 0.05). Minor differences were found in postprandial responses for AAs between MHO and MUO individuals, while three polyunsaturated FAs (linoleic acid, gamma-linolenic acid, arachidonic acid) showed smaller changes in serum after the meal in MHO individuals compared to MUO. Fasting levels for various AAs (notably branched-chain AA) and FAs (e.g., saturated myristic and palmitic acids) were found to correlate with glucose and insulin AUC. CONCLUSION: MHO individuals show preserved insulin sensitivity and a greater ability to adapt to a caloric challenge compared to MUO individuals. PMID- 26274805 TI - A Near-Infrared Photothermal Effect-Responsive Drug Delivery System Based on Indocyanine Green and Doxorubicin-Loaded Polymeric Micelles Mediated by Reversible Diels-Alder Reaction. AB - Near-infrared light (NIR) possesses great advantages for light-responsive controllable drug release, such as deep tissue penetration and low damage to healthy tissues. Herein, a NIR-responsive drug delivery system is developed based on a NIR dye, indocyanine green (ICG), and anticancer drug, doxorubicin (DOX) loaded thermoresponsive block copolymer micelles, in which the drug release can be controlled via NIR irradiation. First, block copolymers, poly(oligo(ethylene glycol) methacrylate)-block-poly(furfuryl methacrylate) (POEGMA-b-PFMA), are synthesized by sequential reversible addition-fragmentation chain-transfer (RAFT) polymerization, followed by modification with N-octyl maleimide through Diels Alder (DA) reaction to produce POEGMA-b-POMFMA. The self-assembly of POEGMA-b POMFMA by nano-precipitation in aqueous solution affords the polymeric micelles which are used to simultaneously encapsulate ICG and DOX. Upon irradiation by NIR light (805 nm), the loaded DOX is released rapidly from the micelles due to partial retro DA reaction and local temperature increase-induced faster drug diffusion by the photothermal effect. Cytotoxicity evaluation and intracellular distribution observation demonstrate significant synergistic effects of NIR triggered drug release, photothermal, and chemotherapy toward cancer cells under NIR irradiation. PMID- 26274806 TI - Menstrual cycle phase and single tablet antiretroviral medication adherence in women with HIV. AB - Suboptimal adherence to antiretroviral (ARV) therapy among HIV-infected individuals is associated with increased risk of progression to AIDS and the development of HIV resistance to ARV medications. To examine whether the luteal phase of the menstrual cycle is independently associated with suboptimal adherence to single tablet regimen (STR) ARV medication, data were analyzed from a multicenter cohort study of HIV-infected women who reported regular menstrual cycles and were taking an STR. In a cross-sectional analysis, suboptimal adherence to an STR among women in their follicular phase was compared with suboptimal adherence among women in their luteal phase. In two-way crossover analyses, whereby the same woman was assessed for STR medication adherence in both her follicular and luteal phases, the estimated exact conditional odds of non-adherence to an STR was measured. In adjusted logistic regression analysis of the cross-sectional data (N=327), women with <=12 years of education were more than three times more likely to have suboptimal adherence (OR=3.6, p=.04) compared to those with >12 years of education. Additionally, women with Center for Epidemiological Studies Depression Scale (CES-D) scores >=23 were 2.5-times more likely to have suboptimal adherence (OR=2.6, p=.02) compared to those with CES-D scores <23. In conditional logistic regression analyses of the crossover data (N=184), having childcare responsibilities was associated with greater odds of <=95% adherence. Menstrual cycle phase was not associated with STR adherence in either the cross-sectional or crossover analyses. The lack of association between phase of the menstrual cycle and adherence to an STR in HIV-infected women means attention can be given to other more important risk factors for suboptimal adherence, such as depression, level of education, and childcare responsibilities. PMID- 26274807 TI - Osteopontin Deficiency Accelerates Spontaneous Colitis in Mice with Disrupted Gut Microbiota and Macrophage Phagocytic Activity. AB - BACKGROUND: Osteopontin (OPN) is a multifunctional protein expressed in a variety of tissues and cells. Recent studies revealed increased OPN expression in the inflamed intestinal tissues of patients with inflammatory bowel disease (IBD). The role of OPN in the pathophysiology of IBD, however, remains unclear. AIMS: To investigate the role of OPN in the development of intestinal inflammation using a murine model of IBD, interleukin-10 knock out (IL-10 KO) mice. METHODS: We compared the development of colitis between IL-10 KO and OPN/IL-10 double KO (DKO) mice. OPN expression in the colonic tissues of IL-10 KO mice was examined by fluorescence in situ hybridization (FISH) analysis. Enteric microbiota were compared between IL-10 KO and OPN/IL-10 DKO mice by terminal restriction fragment length polymorphism analysis. The effect of OPN on macrophage phagocytic function was evaluated by phagocytosis assay. RESULTS: OPN/IL-10 DKO mice had an accelerated onset of colitis compared to IL-10 KO mice. FISH analysis revealed enhanced OPN synthesis in the colonic epithelial cells of IL-10 KO mice. OPN/IL 10 DKO mice had a distinctly different enteric bacterial profile with a significantly lower abundance of Clostridium subcluster XIVa and a greater abundance of Clostridium cluster XVIII compared to IL-10 KO mice. Intracellular OPN deletion in macrophages impaired phagocytosis of fluorescence particle conjugated Escherichia coli in vitro. Exogenous OPN enhanced phagocytosis by OPN deleted macrophages when administered at doses of 1 to 100 ng/ml, but not 1000 ng/ml. CONCLUSIONS: OPN deficiency accelerated the spontaneous development of colitis in mice with disrupted gut microbiota and macrophage phagocytic activity. PMID- 26274808 TI - Bispyridinium Compounds Inhibit Both Muscle and Neuronal Nicotinic Acetylcholine Receptors in Human Cell Lines. AB - Standard treatment of poisoning by organophosphorus anticholinesterases uses atropine to reduce the muscarinic effects of acetylcholine accumulation and oximes to reactivate acetylcholinesterase (the effectiveness of which depends on the specific anticholinesterase), but does not directly address the nicotinic effects of poisoning. Bispyridinium molecules which act as noncompetitive antagonists at nicotinic acetylcholine receptors have been identified as promising compounds and one has been shown to improve survival following organophosphorus poisoning in guinea-pigs. Here, we have investigated the structural requirements for antagonism and compared inhibitory potency of these compounds at muscle and neuronal nicotinic receptors and acetylcholinesterase. A series of compounds was synthesised, in which the length of the polymethylene linker between the two pyridinium moieties was increased sequentially from one to ten carbon atoms. Their effects on nicotinic receptor-mediated calcium responses were tested in muscle-derived (CN21) and neuronal (SH-SY5Y) cells. Their ability to inhibit acetylcholinesterase activity was tested using human erythrocyte ghosts. In both cell lines, the nicotinic response was inhibited in a dose dependent manner and the inhibitory potency of the compounds increased with greater linker length between the two pyridinium moieties, as did their inhibitory potency for human acetylcholinesterase activity in vitro. These results demonstrate that bispyridinium compounds inhibit both neuronal and muscle nicotinic receptors and that their potency depends on the length of the hydrocarbon chain linking the two pyridinium moieties. Knowledge of structure activity relationships will aid the optimisation of molecular structures for therapeutic use against the nicotinic effects of organophosphorus poisoning. PMID- 26274809 TI - Two new diterpenes from the seeds of Caesalpinia minax Hance. AB - Molecules with diterpene skeletons often possess valuable medicinal properties. Two new diterpenes 1alpha,6alpha,7beta-triacetoxy-5alpha-hydroxy-14beta-ethyl-O vouacapane (1) and 2alpha-acetoxy-14,15-cyclopimara-7beta,16-diol (2) were isolated from the seeds of Caesalpinia minax Hance. Their structures were established on the basis of extensive spectroscopic analyses, including HR-ESI MS, UV, IR, 1D, and 2D NMR (HSQC, HMBC, NOESY) methods. The stereochemical structure of 1 was confirmed via the circular dichroism spectrum and calculated ECD experiment. The inhibitory activity of nitric oxide production of RAW264.7 macrophages stimulated by lipopolysaccharide of compounds 1 and 2 was evaluated, and compound 1 was found to show significant inhibitory effect. PMID- 26274810 TI - Complex Drop Impact Morphology. AB - The aim of this work is to understand the changes in the observed phenomena during particle-laden drop impact. The impact of millimeter-size drops was investigated onto hydrophilic (glass) and hydrophobic (polycarbonate) substrates. The drops were dispersions of water and spherical and nearly iso-dense hydrophobic particles with diameters of 200 and 500 MUm. The impact was studied by side and bottom view images in the range 150 <= We <= 750 and 7100 <= Re <= 16400. The particles suppressed the appearance of singular jetting and drop partial rebound but promoted splashing, receding breakup, and rupture. The drops with 200 MUm particles spread in two phases: fast and slow, caused by inertial and capillary forces, respectively. Also, the increase in volume fraction of 200 MUm particle led to a linear decrease in the maximum spreading factor caused by the inertia force on both hydrophilic and hydrophobic substrates. The explanation of this reduction was argued to be the result of energy dissipation through frictional losses between particles and the substrate. PMID- 26274811 TI - Overhydration, Cardiac Function and Survival in Hemodialysis Patients. AB - BACKGROUND AND OBJECTIVES: Chronic subclinical volume overload occurs very frequently and may be ubiquitous in hemodialysis (HD) patients receiving the standard thrice-weekly treatment. It is directly associated with hypertension, increased arterial stiffness, left ventricular hipertrophy, heart failure, and eventually, higher mortality and morbidity. We aimed to assess for the first time if the relationship between bioimpedance assessed overhydration and survival is maintained when adjustments for echocardiographic parameters are considered. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: A prospective cohort trial was conducted to investigate the impact of overhydration on all cause mortality and cardiovascular events (CVE), by using a previously reported cut-off value for overhydration and also investigating a new cut-off value derived from our analysis of this specific cohort. The body composition of 221 HD patients from a single center was assessed at baseline using bioimpedance. In 157 patients supplemental echocardiography was performed (echocardiography subgroup). Comparative survival analysis was performed using two cut-off points for relative fluid overload (RFO): 15% and 17.4% (a value determined by statistical analysis to have the best predictive value for mortality in our cohort). RESULTS: In the entire study population, patients considered overhydrated (using both cut-offs) had a significant increased risk for all-cause mortality in both univariate (HR = 2.12, 95%CI = 1.30-3.47 for RFO>15% and HR = 2.86, 95%CI = 1.72-4.78 for RFO>17.4%, respectively) and multivariate (HR = 1.87, 95%CI = 1.12-3.13 for RFO>15% and HR = 2.72, 95%CI = 1.60-4.63 for RFO>17.4%, respectively) Cox survival analysis. In the echocardiography subgroup, only the 17.4% cut-off remained associated with the outcome after adjustment for different echocardiographic parameters in the multivariate survival analysis. The number of CVE was significantly higher in overhydrated patients in both univariate (HR = 2.46, 95%CI = 1.56-3.87 for RFO >15% and HR = 3.67, 95%CI = 2.29-5.89 for RFO >17.4%) and multivariate (HR = 2.31, 95%CI = 1.42-3.77 for RFO >15% and HR = 4.17, 95%CI = 2.48-7.02 for RFO >17.4%) Cox regression analysis. CONCLUSIONS: The study shows that the hydration status is associated with the mortality risk in a HD population, independently of cardiac morphology and function. We also describe and propose a new cut-off for RFO, in order to better define the relationship between overhydration and mortality risk. Further studies are needed to properly validate this new cut-off in other HD populations. PMID- 26274812 TI - Toward Relatively General and Accurate Quantum Chemical Predictions of Solid State (17)O NMR Chemical Shifts in Various Biologically Relevant Oxygen Containing Compounds. AB - Oxygen is an important element in most biologically significant molecules, and experimental solid-state (17)O NMR studies have provided numerous useful structural probes to study these systems. However, computational predictions of solid-state (17)O NMR chemical shift tensor properties are still challenging in many cases, and in particular, each of the prior computational works is basically limited to one type of oxygen-containing system. This work provides the first systematic study of the effects of geometry refinement, method, and basis sets for metal and nonmetal elements in both geometry optimization and NMR property calculations of some biologically relevant oxygen-containing compounds with a good variety of XO bonding groups (X = H, C, N, P, and metal). The experimental range studied is of 1455 ppm, a major part of the reported (17)O NMR chemical shifts in organic and organometallic compounds. A number of computational factors toward relatively general and accurate predictions of (17)O NMR chemical shifts were studied to provide helpful and detailed suggestions for future work. For the studied kinds of oxygen-containing compounds, the best computational approach results in a theory-versus-experiment correlation coefficient (R(2)) value of 0.9880 and a mean absolute deviation of 13 ppm (1.9% of the experimental range) for isotropic NMR shifts and an R(2) value of 0.9926 for all shift-tensor properties. These results shall facilitate future computational studies of (17)O NMR chemical shifts in many biologically relevant systems, and the high accuracy may also help the refinement and determination of active-site structures of some oxygen-containing substrate-bound proteins. PMID- 26274813 TI - Spatial and Temporal Clustering of Chikungunya Virus Transmission in Dominica. AB - Using geo-referenced case data, we present spatial and spatio-temporal cluster analyses of the early spread of the 2013-2015 chikungunya virus (CHIKV) in Dominica, an island in the Caribbean. Spatial coordinates of the locations of the first 417 reported cases observed between December 15th, 2013 and March 11th, 2014, were captured using the Global Positioning System (GPS). We observed a preponderance of female cases, which has been reported for CHIKV outbreaks in other regions. We also noted statistically significant spatial and spatio temporal clusters in highly populated areas and observed major clusters prior to implementation of intensive vector control programs suggesting early vector control measures, and education had an impact on the spread of the CHIKV epidemic in Dominica. A dynamical identification of clusters can lead to local assessment of risk and provide opportunities for targeted control efforts for nations experiencing CHIKV outbreaks. PMID- 26274814 TI - Experimental and Theoretical Study of Reactions of OH Radicals with Hexenols: An Evaluation of the Relative Importance of the H-Abstraction Reaction Channel. AB - C6 hexenols are one of the most significant groups of volatile organic compounds with biogenic emissions. The lack of corresponding kinetic parameters and product information on their oxidation reactions will result in incomplete atmospheric chemical mechanisms and models. In this paper, experimental and theoretical studies are reported for the reactions of OH radicals with a series of C6 hexenols, (Z)-2-hexen-1-ol, (Z)-3-hexen-1-ol, (Z)-4-hexen-1-ol, (E)-2-hexen-1-ol, (E)-3-hexen-1-ol, and (E)-4-hexen-1-ol, at 298 K and 1.01 * 10(5) Pa. The corresponding rate constants were 8.53 +/- 1.36, 10.1 +/- 1.6, 7.86 +/- 1.30, 8.08 +/- 1.33, 9.10 +/- 1.50, and 7.14 +/- 1.20 (in units of 10(-11) cm(3) molecule(-1) s(-1)), respectively, measured by gas chromatography with a flame ionization detector (GC-FID), using a relative technique. Theoretical calculations concerning the OH-addition and H-abstraction reaction channels were also performed for these reactions to further understand the reaction mechanism and the relative importance of the H-abstraction reaction. By contrast to previously reported results, the H-abstraction channel is a non-negligible reaction channel for reactions of OH radicals with these hexenols. The rate constants of the H-abstraction channel are comparable with those for the OH addition channel and contribute >20% for most of the studied alcohols, even >50% for (E)-3-hexen-1-ol. Thus, H-abstraction channels may have an important role in the reactions of these alcohols with OH radicals and must be considered in certain atmospheric chemical mechanisms and models. PMID- 26274815 TI - Regulation of Gene Expression Patterns in Mosquito Reproduction. AB - In multicellular organisms, development, growth and reproduction require coordinated expression of numerous functional and regulatory genes. Insects, in addition to being the most speciose animal group with enormous biological and economical significance, represent outstanding model organisms for studying regulation of synchronized gene expression due to their rapid development and reproduction. Disease-transmitting female mosquitoes have adapted uniquely for ingestion and utilization of the huge blood meal required for swift reproductive events to complete egg development within a 72-h period. We investigated the network of regulatory factors mediating sequential gene expression in the fat body, a multifunctional organ analogous to the vertebrate liver and adipose tissue, of the female Aedes aegypti mosquito. Transcriptomic and bioinformatics analyses revealed that ~7500 transcripts are differentially expressed in four sequential waves during the 72-h reproductive period. A combination of RNA interference gene-silencing and in-vitro organ culture identified the major regulators for each of these waves. Amino acids (AAs) regulate the first wave of gene activation between 3 h and 12 h post-blood meal (PBM). During the second wave, between 12 h and 36 h, most genes are highly upregulated by a synergistic action of AAs, 20-hydroxyecdysone (20E) and the Ecdysone-Receptor (EcR). Between 36 h and 48 h, the third wave of gene activation-regulated mainly by HR3-occurs. Juvenile Hormone (JH) and its receptor Methoprene-Tolerant (Met) are major regulators for the final wave between 48 h and 72 h. Each of these key regulators also has repressive effects on one or more gene sets. Our study provides a better understanding of the complexity of the regulatory mechanisms related to temporal coordination of gene expression during reproduction. We have detected the novel function of 20E/EcR responsible for transcriptional repression. This study also reveals the previously unidentified large-scale effects of HR3 and JH/Met on transcriptional regulation during the termination of vitellogenesis and remodeling of the fat body. PMID- 26274816 TI - Expression of Emotional Arousal in Two Different Piglet Call Types. AB - Humans as well as many animal species reveal their emotional state in their voice. Vocal features show strikingly similar correlation patterns with emotional states across mammalian species, suggesting that the vocal expression of emotion follows highly conserved signalling rules. To fully understand the principles of emotional signalling in mammals it is, however, necessary to also account for any inconsistencies in the way that they are acoustically encoded. Here we investigate whether the expression of emotions differs between call types produced by the same species. We compare the acoustic structure of two common piglet calls-the scream (a distress call) and the grunt (a contact call)-across three levels of arousal in a negative situation. We find that while the central frequency of calls increases with arousal in both call types, the amplitude and tonal quality (harmonic-to-noise ratio) show contrasting patterns: as arousal increased, the intensity also increased in screams, but not in grunts, while the harmonicity increased in screams but decreased in grunts. Our results suggest that the expression of arousal depends on the function and acoustic specificity of the call type. The fact that more vocal features varied with arousal in scream calls than in grunts is consistent with the idea that distress calls have evolved to convey information about emotional arousal. PMID- 26274817 TI - Changing Kidney Allograft Histology Early Posttransplant: Prognostic Implications of 1-Year Protocol Biopsies. AB - Allograft histology 1 year posttransplant is an independent correlate to long term death-censored graft survival. We assessed prognostic implications of changes in histology first 2 years posttransplant in 938 first kidney recipients, transplanted 1999-2010, followed for 93.4 +/- 37.7 months. Compared to implantation biopsies, histology changed posttransplant showing at 1 year that 72.6% of grafts had minor abnormalities (favorable histology), 20.2% unfavorable histology, and 7.2% glomerulonephritis. Compared to favorable, graft survival was reduced in recipients with unfavorable histology (hazards ratio [HR] = 4.79 [3.27 7.00], p < 0.0001) or glomerulonephritis (HR = 5.91 [3.17-11.0], p < 0.0001). Compared to unfavorable, in grafts with favorable histology, failure was most commonly due to death (42% vs. 70%, p < 0.0001) and less commonly due to alloimmune causes (27% vs. 10%, p < 0.0001). In 80% of cases, favorable histology persisted at 2 years. However, de novo 2-year unfavorable histology (15.3%) or glomerulonephritis (4.7%) related to reduced survival. The proportion of favorable grafts increased during this period (odds ratio = 0.920 [0.871-0.972], p = 0.003, per year) related to fewer DGF, rejections, polyoma-associated nephropathy (PVAN), and better function. Graft survival also improved (HR = 0.718 [0.550-0.937], p = 0.015) related to better histology and function. Evolution of graft histologic early posttransplant relate to long-term survival. Avoiding risk factors associated with unfavorable histology relates to improved histology and graft survival. PMID- 26274818 TI - Multiple Antenatal Dexamethasone Treatment Alters Brain Vessel Differentiation in Newborn Mouse Pups. AB - Antenatal steroid treatment decreases morbidity and mortality in premature infants through the maturation of lung tissue, which enables sufficient breathing performance. However, clinical and animal studies have shown that repeated doses of glucocorticoids such as dexamethasone and betamethasone lead to long-term adverse effects on brain development. Therefore, we established a mouse model for antenatal dexamethasone treatment to investigate the effects of dexamethasone on brain vessel differentiation towards the blood-brain barrier (BBB) phenotype, focusing on molecular marker analysis. The major findings were that in total brains on postnatal day (PN) 4 triple antenatal dexamethasone treatment significantly downregulated the tight junction protein claudin-5, the endothelial marker Pecam-1/CD31, the glucocorticoid receptor, the NR1 subunit of the N-methyl D-aspartate receptor, and Abc transporters (Abcb1a, Abcg2 Abcc4). Less pronounced effects were found after single antenatal dexamethasone treatment and in PN10 samples. Comparisons of total brain samples with isolated brain endothelial cells together with the stainings for Pecam-1/CD31 and claudin-5 led to the assumption that the morphology of brain vessels is affected by antenatal dexamethasone treatment at PN4. On the mRNA level markers for angiogenesis, the sonic hedgehog and the Wnt pathway were downregulated in PN4 samples, suggesting fundamental changes in brain vascularization and/or differentiation. In conclusion, we provided a first comprehensive molecular basis for the adverse effects of multiple antenatal dexamethasone treatment on brain vessel differentiation. PMID- 26274819 TI - Impact of a Mandatory Prescription Drug Monitoring Program on Prescription of Opioid Analgesics by Dentists. AB - Prescription Drug Monitoring Programs (PDMP) are statewide databases that collect data on prescription of controlled substances. New York State mandates prescribers to consult the PDMP registry before prescribing a controlled substance such as opioid analgesics. The effect of mandatory PDMP on opioid drug prescriptions by dentists is not known. This study investigates the impact of mandatory PDMP on frequency and quantity of opioid prescriptions by dentists in a dental urgent care center. Based on the sample size estimate, we collected patient records of a 3-month period before and two consecutive 3-month periods after the mandatory PDMP implementation and analyzed the data on number of visits, treatment types and drug prescriptions using Chi-square tests. For patients who were prescribed pain medications, 452 (30.6%), 190 (14.1%), and 140 (9.6%) received opioid analgesics in the three study periods respectively, signifying a statistically significant reduction in the number of opioid prescriptions after implementation of the mandatory PDMP (p<0.05). Total numbers of prescribed opioid pills in a 3-month period decreased from 5096 to 1120, signifying a 78% reduction in absolute quantity. Prescriptions for non-opioid analgesics acetaminophen increased during the same periods (p<0.05). We conclude that the mandatory PDMP significantly affected the prescription pattern for pain medications by dentists. Such change in prescription pattern represents a shift towards the evidence-based prescription practices for acute postoperative pain. PMID- 26274820 TI - A Regulatory MDM4 Genetic Variant Locating in the Binding Sequence of Multiple MicroRNAs Contributes to Susceptibility of Small Cell Lung Cancer. AB - A functional rs4245739 A>C single nucleotide polymorphism (SNP) locating in the MDM43'-untranslated (3'-UTR) region creates a miR-191-5p or miR-887-3p targeting sites. This change results in decreased expression of oncogene MDM4. Therefore, we examined the association between this SNP and small cell lung cancer (SCLC) risk as well as its regulatory function in SCLC cells. Genotypes were determined in two independent case-control sets consisted of 520SCLC cases and 1040 controls from two regions of China. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. The impact of the rs4245739 SNP on miR-191 5p/miR-887-3p mediated MDM4 expression regulation was investigated using luciferase reporter gene assays. We found that the MDM4 rs4245739AC and CC genotypes were significantly associated with decreased SCLC susceptibility compared with the AA genotype in both case-control sets (Shandong set: OR = 0.53, 95% CI = 0.32-0.89, P = 0.014; Jiangsu set: OR = 0.47, 95% CI = 0.26-0.879, P = 0.017). Stratified analyses indicated that there was a significantly multiplicative interaction between rs4245739 and smoking (Pinteractioin = 0.048). After co-tranfection of miRNAs and different allelic-MDM4 reporter constructs into SCLC cells, we found that the both miR-191-5p and miR-887-3p can lead to significantly decreased MDM4 expression activities in the construct with C allelic 3'-UTR but not A-allelic 3'-UTR, suggesting a consistent genotype phenotype correlation. Our data illuminate that the MDM4rs4245739SNP contributes to SCLC risk and support the notion that gene 3'-UTR genetic variants, impacting miRNA-binding, might modify SCLC susceptibility. PMID- 26274821 TI - Influence of the LILRA3 Deletion on Multiple Sclerosis Risk: Original Data and Meta-Analysis. AB - BACKGROUND: Multiple sclerosis (MS) is a neurodegenerative, autoimmune disease of the central nervous system. Genome-wide association studies (GWAS) have identified over hundred polymorphisms with modest individual effects in MS susceptibility and they have confirmed the main individual effect of the Major Histocompatibility Complex. Additional risk loci with immunologically relevant genes were found significantly overrepresented. Nonetheless, it is accepted that most of the genetic architecture underlying susceptibility to the disease remains to be defined. Candidate association studies of the leukocyte immunoglobulin-like receptor LILRA3 gene in MS have been repeatedly reported with inconsistent results. OBJECTIVES: In an attempt to shed some light on these controversial findings, a combined analysis was performed including the previously published datasets and three newly genotyped cohorts. Both wild-type and deleted LILRA3 alleles were discriminated in a single-tube PCR amplification and the resulting products were visualized by their different electrophoretic mobilities. RESULTS AND CONCLUSION: Overall, this meta-analysis involved 3200 MS patients and 3069 matched healthy controls and it did not evidence significant association of the LILRA3 deletion [carriers of LILRA3 deletion: p = 0.25, OR (95% CI) = 1.07 (0.95 1.19)], even after stratification by gender and the HLA-DRB1*15:01 risk allele. PMID- 26274822 TI - Simultaneous Hypoxia and Low Extracellular pH Suppress Overall Metabolic Rate and Protein Synthesis In Vitro. AB - BACKGROUND: The tumor microenvironment is characterized by regions of hypoxia and acidosis which are linked to poor prognosis. This occurs due to an aberrant vasculature as well as high rates of glycolysis and lactate production in tumor cells even in the presence of oxygen (the Warburg effect), which weakens the spatial linkage between hypoxia and acidosis. METHODS: Five different human squamous cell carcinoma cell lines (SiHa, FaDuDD, UTSCC5, UTSCC14 and UTSCC15) were treated with hypoxia, acidosis (pH 6.3), or a combination, and gene expression analyzed using microarray. SiHa and FaDuDD were chosen for further characterization of cell energetics and protein synthesis. Total cellular ATP turnover and relative glycolytic dependency was determined by simultaneous measurements of oxygen consumption and lactate synthesis rates and total protein synthesis was determined by autoradiographic quantification of the incorporation of 35S-labelled methionine and cysteine into protein. RESULTS: Microarray analysis allowed differentiation between genes induced at low oxygen only at normal extracellular pH (pHe), genes induced at low oxygen at both normal and low pHe, and genes induced at low pHe independent of oxygen concentration. Several genes were found to be upregulated by acidosis independent of oxygenation. Acidosis resulted in a more wide-scale change in gene expression profiles than hypoxia including upregulation of genes involved in the translation process, for example Eukaryotic translation initiation factor 4A, isoform 2 (EIF4A2), and Ribosomal protein L37 (RPL37). Acidosis suppressed overall ATP turnover and protein synthesis by 50%. Protein synthesis, but not total ATP production, was also suppressed under hypoxic conditions. A dramatic decrease in ATP turnover (SiHa) and protein synthesis (both cell lines) was observed when hypoxia and low pHe were combined. CONCLUSIONS: We demonstrate here that the influence of hypoxia and acidosis causes different responses, both in gene expression and in de novo protein synthesis, depending on whether the two factors induced alone or overlapping, and as such it is important for in vivo studies to take this into account. PMID- 26274825 TI - Degenerate Effect on the Mobility of Holes in Graphane: A Study Based on Density Functional Theory Coupled with Deformation Potential Theory. AB - The traditional deformation potential method is not able to calculate the charge mobility of heavily doped degenerate semiconductors, in which inter-band scattering is not negligible. To theoretically predict the charge mobility of such semiconductors, an improved deformation potential method is required, in which the deformation potential constant is decomposed into two parts (hydrostatic and uniaxial terms) based on k?p theory to incorporate the inter band scattering between degenerate valence bands. We propose a new method to calculate the heavy- and light-hole mobilities of graphane. The proposed method produces more appropriate values than the traditional methods. Hence, the new method can be applied to other 2D materials with degenerate bands. PMID- 26274824 TI - Adaptive Staircase Measurement of Hand Proprioception. AB - Clinicians and researchers often need to measure proprioception (position sense), for example to monitor the progress of disease, to identify the cause of movement or balance problems, or to ascertain the effects of an intervention. While researchers can use sophisticated equipment to estimate proprioceptive acuity with good precision, clinicians lack this option and must rely on the subjective and imprecise methods currently available in the clinic. Here we describe a novel technique that applies psychometric adaptive staircase procedures to hand proprioception with a simple tablet-style apparatus that could easily be adapted for the clinic. We report test-retest reliability, inter-rater reliability, and construct validity of the adaptive staircase method vs. two other methods that are commonly used in clinical settings: passive motion direction discrimination (PMDD) and matching. As a first step, we focus on healthy adults. Subjects ages 18-82 had their proprioception measured with each of the three techniques, at the metacarpophalangeal joint in the second finger of the right hand. A subset completed a second session in which the measures were repeated, to assess test retest reliability. Another subset had the measurements done by two different testers to assess inter-rater reliability. Construct validity was assessed using stepwise regression on age and activity level, and correlations calculated across the three methods. Results suggest that of the three methods, the adaptive staircase method yields the best test-retest reliability, inter-rater reliability, and construct validity. The adaptive staircase method may prove to be a valuable clinical tool where more accurate assessment of proprioception is needed. PMID- 26274826 TI - Activation of Strong Boron-Fluorine and Silicon-Fluorine sigma-Bonds: Theoretical Understanding and Prediction. AB - The oxidative addition of BF3 to a platinum(0) bis(phosphine) complex [Pt(PMe3)2] (1) was investigated by density functional calculations. Both the cis and trans pathways for the oxidative addition of BF3 to 1 are endergonic (DeltaG degrees =26.8 and 35.7 kcal mol(-1), respectively) and require large Gibbs activation energies (DeltaG degrees (?)=56.3 and 38.9 kcal mol(-1), respectively). A second borane plays crucial roles in accelerating the activation; the trans oxidative addition of BF3 to 1 in the presence of a second BF3 molecule occurs with DeltaG degrees (?) and DeltaG degrees values of 10.1 and -4.7 kcal mol(-1), respectively. DeltaG degrees (?) becomes very small and DeltaG degrees becomes negative. A charge transfer (CT), F->BF3, occurs from the dissociating fluoride to the second non-coordinated BF3. This CT interaction stabilizes both the transition state and the product. The B-F sigma-bond cleavage of BF2Ar(F) (Ar(F)=3,5-bis(trifluoromethyl)phenyl) and the B-Cl sigma-bond cleavage of BCl3 by 1 are accelerated by the participation of the second borane. The calculations predict that trans oxidative addition of SiF4 to 1 easily occurs in the presence of a second SiF4 molecule via the formation of a hypervalent Si species. PMID- 26274823 TI - The Relationship of Metabolic Syndrome with Stress, Coronary Heart Disease and Pulmonary Function--An Occupational Cohort-Based Study. AB - BACKGROUND AND AIMS: Higher levels of stress impact the prevalence of metabolic syndrome (MetS) and coronary heart disease. The association between MetS, impaired pulmonary function and low level of physical activity is still pending assessment in the subjects exposed to stress. The study aimed to examine whether higher levels of stress might be related to MetS and the plaque presence, as well as whether MetS might affect pulmonary function. DESIGN AND METHODS: The study embraced 235 police officers (mean age 40.97 years) from the south of Poland. The anthropometrics and biochemical variables were measured; MetS was diagnosed using the International Diabetes Federation criteria. Computed tomography coronary angiography of coronary arteries, exercise ECG, measurements of brachial flow mediated dilation, and carotid artery intima-media thickness were completed. In order to measure the self-perception of stress, 10-item Perceived Stress Scale (PSS-10) was applied. Pulmonary function and physical activity levels were also addressed. Multivariate logistic regression analyses were applied to determine the relationships between: 1/ incidence of coronary plaque and MetS per se, MetS components and the number of classical cardiovascular risk factors, 2/ perceived stress and MetS, 3/ MetS and pulmonary function parameters. RESULTS: Coronary artery atherosclerosis was less associated with MetS (OR = 2.62, 95%CI 1.24-5.52; p = 0.011) than with a co-existence of classical cardiovascular risk factors (OR = 5.67, 95% CI 1.07-29.85, p = 0.03; for 3 risk factors and OR = 9.05; 95% CI 1.24-66.23, p = 0.02; for 6 risk factors, respectively). Perceived stress increased MetS prevalence (OR = 1.07, 95% CI 1.03-1.13; p = 0.03), and impacted coronary plaque prevalence (OR = 1.05, 95% CI 1.001-1.10; p = 0.04). Leisure-time physical activity reduced the chances of developing MetS (OR = 0.98 95% CI 0.96 0.99; p = 0.02). MetS subjects had significantly lower values of certain pulmonary function parameters. CONCLUSIONS: Exposure to job-specific stress among police officers increased the prevalence of MetS and impacted coronary plaque presence. MetS subjects had worse pulmonary function parameters. Early-stage, comprehensive therapeutic intervention may reduce overall risk of cardiovascular events and prevent pulmonary function impairment in this specific occupational population. PMID- 26274827 TI - Testing the Short-Term Efficacy of a Lipid-Lowering Nutraceutical in the Setting of Clinical Practice: A Multicenter Study. AB - The main guidelines for cardiovascular disease prevention suggest that nutraceuticals could be an efficacious tool to improve lipid pattern. Our aim was to carry out a clinical trial comparing the metabolic effects of a combined nutraceutical containing both red yeast rice and polyunsaturated fatty acids (PUFAs) and a phytosterol-based approach in a setting of clinical practice. This was a multicenter open study with parallel control. We consecutively enrolled 107 pharmacologically untreated subjects affected by primary polygenic hypercholesterolemia and metabolic syndrome, assigned to 8-week treatment with a combined treatment with red yeast rice (Dif1Stat((r)), including 5 mg monacolin K) and 610 mg PUFAs. A parallel group of 30 subjects with similar characteristics was treated with phytosterols 1600 mg/die. In the combined nutraceutical group, compared with the baseline level, we observed a significant decrease in total cholesterol (TC; -42.50 +/- 18.1 mg/dL), low-density lipoprotein cholesterol (LDL C; -37.6 +/- 13.6 mg/dL), triglycerides (TG; -19.8 +/- 25.1 mg/dL), and non-HDL-C (-43.1 +/- 17.7 mg/dL) (all P < .001). In the phytosterol-treated group, compared to the baseline level, we observed a significant decrease in TC (-13.7 +/- 4.3 mg/dL), LDL-C (-17.6 +/- 8.5 mg/dL), and non-HDL-C (-14.1 +/- 5.6 mg/dL) (all P < .001). When comparing the combined nutraceutical effect with that of phytosterols, we observed that the combined nutraceutical intake was associated with a significantly higher decrease in TC, LDL-C, TG, and non-HDL-C (all P < .001). In the short term, a combined nutraceutical containing red yeast rice and PUFAs is well tolerated and efficacious in reducing plasma lipid levels in subjects affected by primary polygenic hypercholesterolemia and metabolic syndrome. PMID- 26274829 TI - Correction: De Novo Assembly and Characterization of Fruit Transcriptome in Black Pepper (Piper nigrum). PMID- 26274828 TI - Tropism and Induction of Cytokines in Human Embryonic-Stem Cells-Derived Neural Progenitors upon Inoculation with Highly- Pathogenic Avian H5N1 Influenza Virus. AB - Central nervous system (CNS) dysfunction caused by neurovirulent influenza viruses is a dreaded complication of infection, and may play a role in some neurodegenerative conditions, such as Parkinson-like diseases and encephalitis lethargica. Although CNS infection by highly pathogenic H5N1 virus has been demonstrated, it is unknown whether H5N1 infects neural progenitor cells, nor whether such infection plays a role in the neuroinflammation and neurodegeneration. To pursue this question, we infected human neural progenitor cells (hNPCs) differentiated from human embryonic stem cells in vitro with H5N1 virus, and studied the resulting cytopathology, cytokine expression, and genes involved in the differentiation. Human embryonic stem cells (BG01) were maintained and differentiated into the neural progenitors, and then infected by H5N1 virus (A/Chicken/Thailand/CUK2/04) at a multiplicity of infection of 1. At 6, 24, 48, and 72 hours post-infection (hpi), cytopathic effects were observed. Then cells were characterized by immunofluorescence and electron microscopy, supernatants quantified for virus titers, and sampled cells studied for candidate genes.The hNPCs were susceptible to H5N1 virus infection as determined by morphological observation and immunofluorescence. The infection was characterized by a significant up-regulation of TNF-alpha gene expression, while expressions of IFN-alpha2, IFN-beta1, IFN-gamma and IL-6 remained unchanged compared to mock infected controls. Moreover, H5N1 infection did not appear to alter expression of neuronal and astrocytic markers of hNPCs, such as beta-III tubulin and GFAP, respectively. The results indicate that hNPCs support H5N1 virus infection and may play a role in the neuroinflammation during acute viral encephalitis. PMID- 26274830 TI - The use of a potential novel tool in virtual crossmatching for platelet transfusion in platelet refractoriness. AB - BACKGROUND AND OBJECTIVES: Transfusion support for immune-mediated platelet refractoriness (PR) is clinically challenging, technically laborious and costly. The development of 'EpHLA/EpVix software' has been used successfully to select kidney donors. Here, we sought to evaluate this new software as a tool for platelet virtual crossmatch (VxM). MATERIALS AND METHODS: This is a prospective study from 2007 to 2014 of PR patients in a tertiary hospital. Platelet components selected by HLAMatchmaker program were crossmatched by EpHLA/EpVix, anti-human globulin complement-dependent lymphocytotoxicity test (AHG-CDC), flow cytometry platelet crossmatch (FCxM) and then compared. Effectiveness of platelet components transfused was evaluated by CCI. RESULTS: Ninety-seven crossmatched platelet transfusions for 27 patients were enrolled. Partial matches were analysed for 75 transfusions by the 3 methods, and 22% showed discrepant results among the assays. After further analysis, data showed that all divergent cases could be explained by HPA alloimmunization, prozone effect (FCxM), low sensitivity of AHG-CDC and possible interference in FCxM/AHG-CDC assays. Notably, sensitivity and specificity of VxM analysis was excellent (100%). Satisfactory CCI counts were obtained for the majority (22/30) of the transfusions. CONCLUSION: The new EpHLA/EpVix method showed to be effective, feasible and fast for VxM at no cost and able to minimize labour on donor identification. However, platelet crossmatching may be a necessary step because EpHLA/EpVix does not formally exclude HPA alloimmunization. PMID- 26274831 TI - Comparing Health-Care Providers' Perspectives on Complementary and Alternative Medicine in Childhood Cancer Between Netherlands and Indonesia. AB - BACKGROUND: Use of complementary and alternative medicine (CAM) is common among patients with childhood cancer. Health-care providers (HCP) should address this need properly. Geographical and cultural differences seem likely. This study explores perspectives on CAM of HCP involved in the care of children with cancer in Netherlands and Indonesia. Health beliefs, components of CAM, encouraging or discouraging CAM, and knowledge about CAM were assessed. PROCEDURE: We conducted a cross-sectional study using semi-structured questionnaires at a Dutch and Indonesian academic hospital. RESULTS: A total of 342 HCP participated: 119 Dutch (response rate 80%) and 223 Indonesian (response rate 87%). Chemotherapy can cure cancer according to more Dutch than Indonesian HCP (87% vs. 53% respectively, P < 0.001). Combination of chemotherapy and CAM is the best way to cure cancer according to more Indonesian than Dutch HCP (45% vs. 25%, P < 0.001). Dutch and Indonesian HCP recommend and discourage CAM use differently. Most Dutch (77%) and Indonesian HCP (84%) consider their knowledge about CAM to be inadequate (P = ns). Fewer Dutch doctors than other HCP want to learn more about CAM (51% vs. 76%, P = 0.007), whereas there is no significant difference in eagerness to learn about CAM between Indonesian doctors (64%) and other HCP (72%). CONCLUSIONS: Indonesian HCP have more positive views about CAM than their Dutch colleagues. Both Dutch and Indonesian HCP consider their knowledge about CAM to be inadequate. Therefore, education programs about CAM tailored to the needs of HCP are recommended, knowing that CAM is used frequently. PMID- 26274832 TI - At the crossroads of glaucoma and neuro-ophthalmology. PMID- 26274833 TI - Glaucoma as a neurodegenerative disease. AB - BACKGROUND: The primary pathophysiological feature of glaucoma is a progressive optic neuropathy with characteristic morphological changes of the optic disc and risk factors of age and intraocular pressure. Recently, involvement of other areas of the central nervous system (CNS) beyond the optic nerve has been demonstrated. This article addresses the proposition that glaucoma shares mechanistic and pathophysiologic features with neurodegenerations in the CNS. METHODS: The literature on CNS alterations in patients with glaucoma is reviewed with particular focus on neuroimaging and pathological studies. A theoretical framework for assessing whether glaucoma is truly a neurodegenerative disease is developed based on the comparison with neurodegenerative and nonneurodegenerative diseases. RESULTS: Although there is convincing evidence of abnormalities in CNS regions distal to the optic nerve in glaucoma, these are similar to those seen in other disorders of the proximal visual pathways, such as other optic neuropathies or retinal diseases. Similarly, features of glaucoma that are similar to neurodegenerations are also seen in nonneurodegenerative diseases. CONCLUSIONS: Glaucoma is less likely a primary neurodegeneration affecting the CNS and more likely a primary optic neuropathy with secondary effects in the CNS. PMID- 26274834 TI - Central visual pathways in glaucoma: evidence for distal mechanisms of neuronal self-repair. AB - As in other age-related neurodegenerative diseases, progression of neurodegeneration in glaucoma involves early axonopathy. In glaucoma, this is marked by degradation of active transport along retinal ganglion cell (RGC) axons projecting from the retina to the brain. In experimental systems, transport degradation occurs first in the most distal site in the RGC projection, the superior colliculus (SC) of the midbrain. Even as degradation progresses from one retinotopic sector to the next, important structures in the affected sectors persist, including synapses from RGC axon terminals onto SC neurons. This structural persistence is accompanied by focally increased brain-derived neurotrophic factor in hypertrophic SC astrocyte glia and defines a therapeutic window of opportunity. Thus, central brain structures in glaucoma may respond to disease-relevant stress by induction of mechanisms useful for maintaining retinal signals. PMID- 26274835 TI - Intracranial pressure and glaucoma. AB - Our understanding of the potential role intracranial pressure (ICP) may play in the pathophysiology of glaucoma is evolving. ICP can have a profound effect on the optic nerve; edema of the optic disc is an accepted consequence of elevation in ICP, and optic disc blood flow is known to be affected by ICP. Deformation of the orbit also is a known consequence of aberrations in ICP. Therefore, it is plausible that local alterations in optic nerve structure, blood supply, or axonal transport could result from changes in ICP. This article will summarize the relationship between ICP and the eye, specifically focusing on hypothesized relationships between ICP and glaucoma and the current evidence supporting or refuting ICP as a risk factor for glaucoma. PMID- 26274836 TI - Phenotypic differences in normal vs high tension glaucoma. AB - BACKGROUND: Normal tension glaucoma (NTG) and high tension open angle glaucoma (HTG) are associated with characteristic patterns of optic nerve findings and corresponding patterns of visual field loss. In the past, clinicians viewed NTG and HTG as distinct entities, with separate underlying pathophysiologies and often different clinical presentations and courses. METHODS: Literature review. RESULTS: Optic nerve and visual field findings in NTG have been reported to be dissimilar to those in HTG. In more recent years, however, there has been increasing recognition of the shared features NTG and HTG. CONCLUSION: There is now a trend to consider these two entities as part of a spectrum of glaucoma with overlapping pathophysiology and clinical characteristics. PMID- 26274837 TI - The morphological difference between glaucoma and other optic neuropathies. AB - The clinical phenomenon of cupping has 2 principal pathophysiologic components in all optic neuropathies: prelaminar thinning and laminar deformation. We define prelaminar thinning to be the portion of cup enlargement that results from thinning of the prelaminar tissues due to physical compression and/or loss of retinal ganglion cell axons. We define laminar deformation or laminar cupping to be the portion of cup enlargement that results from permanent intraocular pressure (IOP)-induced deformation of the lamina cribrosa and peripapillary scleral connective tissues after damage and/or remodeling. We propose that the defining phenomenon of glaucomatous cupping is deformation and/or remodeling of the neural and connective tissues of the optic nerve head (ONH), which is governed by the distribution of IOP-related connective tissue stress and strain, regardless of the mechanism of insult or the level of IOP at which deformation and/or remodeling occurs. In other words, "glaucomatous cupping" is the term clinicians use to describe the clinical appearance and behavior the ONH assumes as its neural and connective tissues deform, remodel, or mechanically fail: 1) in a pattern and 2) by the several pathophysiologic processes governed by IOP related connective tissue stress and strain. ONH biomechanics explains why a given ONH will demonstrate a certain form of "cupping" and at what level of IOP that might happen. Animal models are allowing us to tease apart the important components of cupping in IOP-related and non-IOP-related forms of optic neuropathy. A paradigm change in spectral domain optical coherence tomography ONH, retinal nerve fiber layer, and macular imaging should improve our ability to phenotype the ocular manifestations of many forms of damage to the visual system including glaucoma. PMID- 26274839 TI - Projecting the self into the future in individuals with schizophrenia: a preliminary cross-sectional study. AB - The ability to project oneself into the future contributes to development and maintenance of a coherent sense of identity. If recent research has revealed that schizophrenia is associated with difficulties envisioning the future, little is known about patients' future self-representations. In this study, 27 participants with schizophrenia and 26 healthy controls were asked to simulate mental representations of plausible and highly significant future events (self-defining future projections, SDFPs) that they anticipate to happen in their personal future. Main results showed that schizophrenia patients had difficulties in reflecting on the broader meaning and implications of imagined future events. In addition, and contrary to our hypothesis, a large majority of SDFPs in schizophrenia patients were positive events, including achievements, relationship, and leisure contents. Interestingly, patients and controls did not differ on the perceived probability that these events will occur in the future. Our results suggest that schizophrenia patients have an exaggerated positive perception of their future selves. Together, these findings lend support to the idea that past and future self-defining representations have both similar and distinct characteristics in schizophrenia. PMID- 26274838 TI - Chronic Hormonal Imbalance and Adipose Redistribution Is Associated with Hypothalamic Neuropathology following Blast Exposure. AB - Endocrine disorders have been shown to be a consequence of blast traumatic brain injury in soldiers returning from military conflicts. Hormone deficiency and adrenocorticotropic hormone (ACTH) dysfunction can lead to symptoms such as fatigue, anxiety, irritability, insomnia, sexual dysfunction, and decreased quality of life. Given these changes following blast exposure, the current study focused on investigating chronic pathology within the hypothalamus following blast, in addition to systemic effects. An established rodent model of blast neurotrauma was used to induce mild blast-induced neurotrauma. Adipose tissue, blood, and brain samples were collected at one and three months following a single blast exposure. Adipose tissue and blood were evaluated for changes in ACTH, adiponectin, C-reactive protein, glial fibrillary acidic protein, interleukin (IL)-1beta, and leptin. The hypothalamus was evaluated for injury using immunohistochemical techniques. The results demonstrated that the weight of the blast animals was significantly less, compared with the sham group. The slower rate of increase in their weight was associated with changes in ACTH, IL 1beta, and leptin levels. Further, histological analysis indicated elevated levels of cleaved caspase-3 positive cells within the hypothalamus. The data suggest that long-term outcomes of brain injury occurring from blast exposure include dysfunction of the hypothalamus, which leads to compromised hormonal function, elevated biological stress-related hormones, and subsequent adipose tissue remodeling. PMID- 26274840 TI - Cerebellar transcranial direct current stimulation in patients with ataxia: A double-blind, randomized, sham-controlled study. AB - BACKGROUND AND OBJECTIVE: Numerous studies have highlighted the possibility of modulating the excitability of cerebellar circuits using transcranial direct current stimulation. The present study investigated whether a single session of cerebellar anodal transcranial direct current stimulation could improve symptoms in patients with ataxia. METHODS: Nineteen patients with ataxia underwent a clinical and functional evaluation pre- and post-double-blind, randomized, sham, or anodal transcranial direct current stimulation. RESULTS: There was a significant interaction between treatment and time on the Scale for the Assessment and Rating of Ataxia, on the International Cooperative Ataxia Rating Scale, on the 9-Hole Peg Test, and on the 8-Meter Walking Time (P < 0.001). At the end of the sessions, all performance scores were significantly different in the sham trial, compared to the intervention trial. CONCLUSIONS: A single session of anodal cerebellar transcranial direct current stimulation can transiently improve symptoms in patients with ataxia and might represent a promising tool for future rehabilitative approaches. PMID- 26274842 TI - Enzymes and bioproducts produced by the ascomycete fungus Paecilomyces variotii. AB - Due its innate ability to produce extracellular enzymes which can provide eco friendly solutions for a variety of biotechnological applications, Paecilomyces variotii is a potential source of industrial bioproducts. In this review, we report biotechnological records on the biochemistry of different enzymes produced by the fermentation of the P. variotii fungus, including tannases, phytases, cellulases, xylanases, chitinases, amylases and pectinases. Additionally, the main physicochemical properties which can affect the enzymatic reactions of the enzymes involved in the conversion of a huge number of substrates to high-value bioproducts are described. Despite all the background information compiled in this review, more research is required to consolidate the catalytic efficiency of P. variotii, which must be optimized so that it is more accurate and reproducible on a large scale. PMID- 26274841 TI - Density-Dependent Metabolic Heterogeneity in Human Mesenchymal Stem Cells. AB - Human mesenchymal stem cells (hMSCs) are intrinsically heterogeneous and comprise subpopulations that differ in their proliferation, multi-potency, and functional properties, which are commonly demonstrated by culturing hMSCs at different plating densities. The objective of this study was to investigate the metabolic profiles of different subpopulations of hMSC by testing the hypothesis that the clonogenic hMSC subpopulation, which is selectively enriched in clonal density (CD) and low density (LD) culture (10 and 100 cells per square centimeter, respectively), possesses a metabolic phenotype that differs from that of hMSC in medium- or high-density (MD: 1,000 and HD: 3,000 cells per square centimeter, respectively). Cells at CD and LD conditions exhibited elevated expression of CD146 and colony forming unit-fibroblast compared with cells at MD- or HD. Global metabolic profiles revealed by gas chromatography-mass spectrometry of cell extracts showed clear distinction between LD and HD cultures, and density dependent differences in coupling of glycolysis to the TCA cycle. Metabolic inhibitors revealed density-dependent differences in glycolysis versus oxidative phosphorylation (OXPHOS) for ATP generation, in glutamine metabolism, in the dependence on the pentose phosphate pathway for maintaining cellular redox state, and sensitivity to exogenous reactive oxygen species. We also show that active OXPHOS is not required for proliferation in LD culture but that OXPHOS activity increases senescence in HD culture. Together, the results revealed heterogeneity in hMSC culture exists at the level of primary metabolism. The unique metabolic characteristics of the clonogenic subpopulation suggest a novel approach for optimizing in vitro expansion of hMSCs. PMID- 26274843 TI - Metabolomics confirms that dissolved organic carbon mitigates copper toxicity. AB - Reductions in atmospheric emissions from the metal smelters in Sudbury, Canada, produced major improvements in acid and metal contamination of local lakes and indirectly increased dissolved organic carbon (DOC) concentrations. Metal toxicity, however, has remained a persistent problem for aquatic biota. Integrating high-throughput, nontargeted mass spectrometry metabolomics with conventional toxicological measures elucidated the mediating effects of dissolved organic matter (DOM) on the toxicity of Cu to Daphnia pulex-pulicaria, a hybrid isolated from these soft water lakes. Two generations of daphniids were exposed to Cu (0-20 MUg/L) at increasing levels of natural DOM (0-4 mg DOC/L). Added DOM reduced Cu toxicity monotonically with median lethal concentration values increasing from 2.3 MUg/L Cu without DOM to 22.7 MUg/L Cu at 4 mg DOC/L. Reproductive output similarly benefited, increasing with DOM, yet falling with increases in Cu. Second generation reproduction was more impaired than the first generation. Dissolved organic matter had a greater influence than Cu on the metabolic status of the daphniids. Putative identification of metabolite peaks indicated that DOM elevation increased the metabolic energy status of the first generation animals, but this benefit was reduced in the second generation, although evidence of increased oxidative stress was detected. These results indicate that Sudbury's terrestrial ecosystems should be managed to increase aquatic DOM supply to enable daphniid colonists to both survive and foster stable populations. PMID- 26274844 TI - Walking speed, not muscle mass, is associated with urinary incontinence in community-dwelling old Taiwanese. PMID- 26274845 TI - Editorial. PMID- 26274846 TI - On Murray Jackson's 1961 'Chair, couch and countertransference'. AB - One of the problems facing psychoanalysts of all schools is that theory has evolved at a much faster pace than practice. Whereas there has been an explosion of theory, practice has remained, at least officially, static and unchanging. It is in this sense that Murray Jackson's 1961 paper is still relevant today. Despite the rise of the new relational and intersubjective paradigms, most psychoanalysts, and not a few Jungian analysts, still seem to feel that the couch is an essential component of the analytical setting and process. If the use of the couch is usually justified by the argument that it favours regression, facilitates analytical reverie and protects the patient from the influence of the analyst, over time many important psychoanalysts have come to challenge this position. Increasingly these analysts suggest that the use of the couch may actually be incompatible with the newer theoretical models. This contention is strengthened by some of the findings coming from the neurosciences and infant research. This underlines the necessity of empirical research to verify the clinical effectiveness of these different positions, couch or face-to-face, but it is exactly this type of research that is lacking. PMID- 26274847 TI - The analytic setting today: using the couch or the chair? AB - This paper re-visits Murray Jackson's 1961 paper in the Journal of Analytical Psychology, 'Chair, couch and countertransference', with the aim of exploring the role of the couch for Jungian analysts in clinical practice today. Within the Society of Analytical Psychology (SAP) and some other London-based societies, there has been an evolution of practice from face-to-face sessions with the patient in the chair, as was Jung's preference, to a mode of practice where patients use the couch with the analyst sitting to the side rather than behind, as has been the tradition in psychoanalysis. Fordham was the founding member of the SAP and it was because of his liaison with psychoanalysis and psychoanalysts that this cultural shift came about. Using clinical examples, the author explores the couch/chair question in terms of her own practice and the internal setting as a structure in her mind. With reference to Bleger's (2013) paper 'Psychoanalysis of the psychoanalytic setting', the author discusses how the analytic setting, including use of the couch or the chair, can act as a silent container for the most primitive aspects of the patient's psyche which will only emerge in analysis when the setting changes or is breached. PMID- 26274848 TI - Revisioning Fordham's 'Defences of the self' in light of modern relational theory and contemporary neuroscience. AB - This paper explores the evolution of Michael Fordham's ideas concerning 'defences of the self', including his application of this concept to a group of 'difficult' adult patients in his famous 1974 paper by the same name. After tracing the relevance of Fordham's ideas to my own discovery of a 'self-care system' in the psychological material of early trauma patients (Kalsched ), I describe how Fordham's seminal notions might be revisioned in light of contemporary relational theory as well as early attachment theory and affective neuroscience. These revisionings involve an awareness that the severe woundings of early unremembered trauma are not transformable through interpretation but will inevitably be repeated in the transference, leading to mutual 'enactments' between the analytic partners and, hopefully, to a new outcome. A clinical example of one such mutual enactment between the author and his patient is provided. The paper concludes with reflections on the clinical implications of this difficult case and what it means to become a 'real person' to our patients. Finally, Jung's alchemical views on transference are shown to be useful analogies in our understanding of the necessary mutuality in the healing process with these patients. PMID- 26274849 TI - Michael Fordham and the Journal of Analytical Psychology: the view from Hangman's Hill. AB - This short paper was presented to a conference in honour of the 60(th) year of the JAP and was one of others that acknowledged the contribution of Michael Fordham. The subtitle refers to the paper's overview of Fordham's published oeuvre and the particular place of the Journal of Analytical Psychology, for which he was the founding editor. Fordham's contribution to a Jungian-based model of development is discussed, with reference to his papers in the British Journal of Medical Psychology. The paper notes miscellaneous pieces from Fordham's commentaries, obituaries, papers and reviews which capture not only the development of Fordham as a thinker but also his character. There is discussion of his reviews of Melanie Klein's Envy and Gratitude and manuscripts by Erich Neumann. A reminiscence of Fordham as supervisor is recounted. PMID- 26274850 TI - When symptom is symbol: some comments on Rosemary Gordon's, 'Masochism: the shadow side of the archetypal need to venerate and worship'. AB - This paper is a commentary on Rosemary Gordon's paper, 'Masochism: the shadow side of the archetypal need to venerate and worship', with a suggestion for an alternative interpretation of masochism as a part of a sado-masochistic couple. Gordon postulates an archetypal need to venerate and worship that can be hidden in the shadow and distorted in such practices as sexual masochism. Her paper also offers several avenues of exploration for further studies in connection with the phenomenon of masochism, including sexual perversion ('paraphilia'), chronic psychological victimhood, PTSD and traumatology, religious extremist behaviour such as self-flagellation, transformation in the individuation process and numinous experience. An extension of her hypothesis to include religious problems of modernity is suggested. PMID- 26274851 TI - A revolution of the mind: some implications of George Hogenson's 'The Baldwin Effect: a neglected influence on C.G. Jung's evolutionary thinking' (2001). AB - George Hogenson's 2001 paper 'The Baldwin Effect: a neglected influence on C.G. Jung's evolutionary thinking' developed the radical argument that, if archetypes are emergent, they 'do not exist in the sense that there is no place that the archetypes can be said to be'. In this paper, I show how Hogenson's thinking has been seminal to my own: it is not just archetypes but the mind itself that has no 'place'. The mind is a dynamic system, emergent from the cultural environment of symbolic meanings to which humans are evolutionarily adapted. Drawing on the work of philosopher John Searle, I argue that symbols constitute the realities that they bring forth, including the imaginal realities of the psyche. The implications for clinical work include a rejection of structural models of the psyche in favour of the emergence of symbolic realities in the context of psychoanalysis as a distributed system of cognition. PMID- 26274852 TI - On integrating Jungian and other theories. AB - This paper consists of reflections on some of the processes, subtleties, and 'eros' involved in attempting to integrate Jungian and other analytic perspectives. Assimilation of other theoretical viewpoints has a long history in analytical psychology, beginning when Jung met Freud. Since its inception, the Journal of Analytical Psychology has provided a forum for theoretical syntheses and comparative psychoanalysis. Such attempts at synthesizing other theories represent analytical psychology itself trying to individuate. PMID- 26274854 TI - Gubb, K. (2014). 'Craving interpretation: a case of somatic countertransference'. British Journal of Psychotherapy, 30, 1, 51-67. PMID- 26274853 TI - Moller, M. (2014). 'The analyst's anxieties in the first interview: barriers against analytic presence'. International Journal of Psychoanalysis, 95, 485-503. PMID- 26274855 TI - Ogden, T. (2014). 'Fear of breakdown and the unlived life'. International Journal of Psychoanalysis, 95, 205-23. PMID- 26274856 TI - Ranieri, F. (2014). 'Children who dare too much: child psychotherapy and extreme risk seeking'. Journal of Child Psychotherapy, 40, 2, 173-86. PMID- 26274857 TI - Walsh, S. D. (2014). 'The bilingual therapist and transference to language: language use in therapy and its relationship to object relational context.'. Psychoanalytic Dialogues, 24, 1, 56-71. PMID- 26274858 TI - Durban, J. (2014). 'Despair and hope: on some varieties of countertransference and enactment in the psychoanalysis of ASD (autistic spectrum disorder) children'. Journal of Child Psychotherapy, 40, 2, 187-200. PMID- 26274861 TI - Erratum. PMID- 26274862 TI - Nitrogen-doped dual mesoporous carbon for the selective oxidation of ethylbenzene. AB - A nanocasting method to fabricate nitrogen-doped dual mesoporous carbon is proposed by the carbonization of nitrile functional ionic liquid (FIL) grafted SBA-15 for the first time. These carbon materials have high nitrogen content (12.8%), large specific surface areas (763 m(2) g(-1)) and uniform rod morphologies, which are derived from FILs grafted on the surface of SBA-15. Furthermore, by adjusting the impregnation amount of ionic liquids on SBA-15, pore structures of these carbon materials can be adjusted from single to dual mesopores. The developed dual mesoporous carbon materials exhibit good catalytic performance in the selective oxidation of ethylbenzene, ascribed to the promoting effects of nitrogen-doping, high surface area and dual mesostructure. It may be concluded that the dual mesostructure has an advantage over a single mesostructure to obtain a fast mass transport rate, resulting in higher acetophenone yield. PMID- 26274863 TI - Facile synthesis of anhydrous alkaline earth metal dodecaborates MB12H12 (M = Mg, Ca) from M(BH4)2. AB - Metal dodecaborates M2/nB12H12 are among the dehydrogenation intermediates of metal borohydrides M(BH4)n with a high hydrogen density of approximately 10 mass%, the latter is a potential hydrogen storage material. There is therefore a great need to synthesize anhydrous M2/nB12H12 in order to investigate the thermal decomposition of M2/nB12H12 and to understand its role in the dehydrogenation and rehydrogenation of M(BH4)n. In this work, anhydrous alkaline earth metal dodecaborates MB12H12 (M = Mg, Ca) have been successfully synthesized by sintering M(BH4)2 (M = Mg, Ca) and B10H14 in a stoichiometric molar ratio of 1 : 1. Thermal decomposition of MB12H12 shows multistep pathways with the formation of H-deficient monomers MB12H12-x containing icosahedral B12 skeletons and is followed by the formation of (MByHz)n polymers. Comparison of the thermal decomposition of MB12H12 and M(BH4)2 suggests different behaviours of the anhydrous MB12H12 and those formed from the decomposition of M(BH4)n. PMID- 26274864 TI - Life and Liesegang: Outcrop-Scale Microbially Induced Diagenetic Structures and Geochemical Self-Organization Phenomena Produced by Oxidation of Reduced Iron. AB - The Kanab Wonderstone is sandstone (Shinarump Member, Chinle Formation) that is cemented and stained with iron oxide. The iron-oxide cementation and staining in these rocks have been considered examples of the Liesegang phenomenon, but we will show that they comprise a microbially induced structure. The spacing of bands of iron-oxide stain follow the Jablczynski spacing law (wherein the spacing between bands of iron-oxide stain increases as one traverses a series of bands) characteristic of Liesegang. Bands of iron-oxide cement exhibit more variable spacing and exhibit a weak but significant correlation between band thickness and distance between bands of cement. The pore-filling cement contains morphotypes that are similar in size and habit to those exhibited by microaerophilic iron oxidizing bacteria. Other disseminated iron-oxide mineralization occurs as rhombohedra interpreted to be pseudomorphs after siderite. We interpret the cement to be produced by microbially mediated oxidation of siderite (a typical early diagenetic mineral in fluvial sandstones). Iron-oxidizing bacteria colonized the redox interface between siderite-cemented sand and porous sandstone. Microbes oxidized aqueous Fe(II), generating acid that caused siderite dissolution. The iron-oxide cement is the microbial product of a geochemical drive for organization; whereas the iron-oxide stain is true Liesegang. Together, they comprise a distinctive microbially induced structure with high preservation potential. PMID- 26274865 TI - Extending Galactic Habitable Zone Modeling to Include the Emergence of Intelligent Life. AB - Previous studies of the galactic habitable zone have been concerned with identifying those regions of the Galaxy that may favor the emergence of complex life. A planet is deemed habitable if it meets a set of assumed criteria for supporting the emergence of such complex life. In this work, we extend the assessment of habitability to consider the potential for life to further evolve to the point of intelligence--termed the propensity for the emergence of intelligent life, phiI. We assume phiI is strongly influenced by the time durations available for evolutionary processes to proceed undisturbed by the sterilizing effects of nearby supernovae. The times between supernova events provide windows of opportunity for the evolution of intelligence. We developed a model that allows us to analyze these window times to generate a metric for phiI, and we examine here the spatial and temporal variation of this metric. Even under the assumption that long time durations are required between sterilizations to allow for the emergence of intelligence, our model suggests that the inner Galaxy provides the greatest number of opportunities for intelligence to arise. This is due to the substantially higher number density of habitable planets in this region, which outweighs the effects of a higher supernova rate in the region. Our model also shows that phiI is increasing with time. Intelligent life emerged at approximately the present time at Earth's galactocentric radius, but a similar level of evolutionary opportunity was available in the inner Galaxy more than 2 Gyr ago. Our findings suggest that the inner Galaxy should logically be a prime target region for searches for extraterrestrial intelligence and that any civilizations that may have emerged there are potentially much older than our own. PMID- 26274867 TI - Sandwich-like Microenvironments to Harness Cell/Material Interactions. AB - Cell culture has been traditionally carried out on bi-dimensional (2D) substrates where cells adhere using ventral receptors to the biomaterial surface. However in vivo, most of the cells are completely surrounded by the extracellular matrix (ECM), resulting in a three-dimensional (3D) distribution of receptors. This may trigger differences in the outside-in signaling pathways and thus in cell behavior. This article shows that stimulating the dorsal receptors of cells already adhered to a 2D substrate by overlaying a film of a new material (a sandwich-like culture) triggers important changes with respect to standard 2D cultures. Furthermore, the simultaneous excitation of ventral and dorsal receptors shifts cell behavior closer to that found in 3D environments. Additionally, due to the nature of the system, a sandwich-like culture is a versatile tool that allows the study of different parameters in cell/material interactions, e.g., topography, stiffness and different protein coatings at both the ventral and dorsal sides. Finally, since sandwich-like cultures are based on 2D substrates, several analysis procedures already developed for standard 2D cultures can be used normally, overcoming more complex procedures needed for 3D systems. PMID- 26274868 TI - Predicting three types of dissociation in female survivors of intimate partner violence. AB - Previous research suggests that studying the effect of dissociation is particularly important in survivors of intimate partner violence because of the risk of revictimization. The current study investigated demographic variables, child and current abuse characteristics, coping style, and cognitive distortions as predictors of peritraumatic, trait, and posttraumatic stress disorder (PTSD) related dissociation in a sample of female intimate partner violence survivors. The sample consisted of 372 women, the majority African American, with an average age of 34.41 years (SD = 8.09). Peritraumatic dissociation was significantly predicted by child physical abuse, current abuse injury, cognitive distortions about safety, and problem disengagement coping. Trait dissociation was significantly predicted by minority race, personal income, and cognitive distortions about safety and self-worth. PTSD-related dissociation was significantly predicted by cognitive distortions about self-worth, problem and emotion disengagement coping, and peritraumatic dissociation. In the models predicting both trait and PTSD-related dissociation, abuse characteristics significantly predicted dissociation until the entry of cognitive variables into the model. The analysis indicated a significant indirect effect of cognitive distortions on the relationship between current sexual aggression and trait dissociation. Results also suggested that there were indirect effects of both cognitive distortions and peritraumatic dissociation on the relationships between current psychological abuse/injury and PTSD-related dissociation. Findings point to the importance of cognitions in the development and maintenance of dissociation and suggest that treatments designed to help clients accept and process traumatic events may help reduce dissociation and in turn prevent future revictimization. PMID- 26274866 TI - Neocortical Rebound Depolarization Enhances Visual Perception. AB - Animals are constantly exposed to the time-varying visual world. Because visual perception is modulated by immediately prior visual experience, visual cortical neurons may register recent visual history into a specific form of offline activity and link it to later visual input. To examine how preceding visual inputs interact with upcoming information at the single neuron level, we designed a simple stimulation protocol in which a brief, orientated flashing stimulus was subsequently coupled to visual stimuli with identical or different features. Using in vivo whole-cell patch-clamp recording and functional two-photon calcium imaging from the primary visual cortex (V1) of awake mice, we discovered that a flash of sinusoidal grating per se induces an early, transient activation as well as a long-delayed reactivation in V1 neurons. This late response, which started hundreds of milliseconds after the flash and persisted for approximately 2 s, was also observed in human V1 electroencephalogram. When another drifting grating stimulus arrived during the late response, the V1 neurons exhibited a sublinear, but apparently increased response, especially to the same grating orientation. In behavioral tests of mice and humans, the flashing stimulation enhanced the detection power of the identically orientated visual stimulation only when the second stimulation was presented during the time window of the late response. Therefore, V1 late responses likely provide a neural basis for admixing temporally separated stimuli and extracting identical features in time-varying visual environments. PMID- 26274869 TI - Bullying among adolescents in a Brazilian urban center - "Health in Beaga" Study. AB - OBJECTIVE: To analyze the prevalence of bullying and its associated factors in Brazilian adolescents. METHODS: Data were used from a population-based household survey conducted by the Urban Health Observatory (OSUBH) utilizing probability sampling in three stages: census tracts, residences, and individuals. The survey included 598 adolescents (14-17 years old) who responded questions on bullying, sociodemographic characteristics, health-risk behaviors, educational well-being, family structure, physical activity, markers of nutritional habits, and subjective well-being (body image, personal satisfaction, and satisfaction with their present and future life). Univariate and multivariate analysis was done using robust Poisson regression. RESULTS: The prevalence of bullying was 26.2% (28.0% among males, 24.0% among females). The location of most bullying cases was at or on route to school (70.5%), followed by on the streets (28.5%), at home (9.8%), while practicing sports (7.3%), at parties (4.6%), at work (1.7%), and at other locations (1.6%). Reports of bullying were associated with life dissatisfaction, difficulty relating to parents, involvement in fights with peers and insecurity in the neighborhood. CONCLUSIONS: A high prevalence of bullying among participating adolescents was found, and the school serves as the main bullying location, although other sites such as home, parties and workplace were also reported. Characteristics regarding self-perception and adolescent perceptions of their environment were also associated with bullying, thus advancing the knowledge of this type of violence, especially in urban centers of developing countries. PMID- 26274870 TI - [Religiousness and health-related quality of life of older adults]. AB - OBJECTIVE: To examine whether religiousness mediates the relationship between sociodemographic factors, multimorbidity and health-related quality of life of older adults. METHODS: This population-based cross-sectional study is part of the Survey on Health, Well-Being, and Aging (SABE). The sample was composed by 911 older adults from Sao Paulo, SP, Southeastern Brazil. Structural equation modeling was performed to assess the mediator effect of religiousness on the relationship between selected variables and health-related quality of life of older adults, with models for men and women. The independent variables were: age, education, family functioning and multimorbidity. The outcome variable was health related quality of life of older adults, measured by SF-12 (physical and mental components). The mediator variables were organizational, non-organizational and intrinsic religiousness. Cronbach's alpha values were: physical component = 0.85; mental component = 0.80; intrinsic religiousness = 0.89 and family APGAR (Adaptability, Partnership, Growth, Affection, and Resolve) = 0.91. RESULTS: Higher levels of organizational and intrinsic religiousness were associated with better physical and mental components. Higher education, better family functioning and fewer diseases contributed directly to improved performance in physical and mental components, regardless of religiousness. For women, organizational religiousness mediated the relationship between age and physical (beta = 2.401, p < 0.01) and mental (beta = 1.663, p < 0.01) components. For men, intrinsic religiousness mediated the relationship between education and mental component (beta = 7.158, p < 0.01). CONCLUSIONS: Organizational and intrinsic religiousness had a beneficial effect on the relationship between age, education and health-related quality of life of these older adults. PMID- 26274871 TI - Budget impact from the incorporation of positron emission tomography - computed tomography for staging lung cancers. AB - OBJECTIVE: To estimate the budget impact from the incorporation of positron emission tomography (PET) in mediastinal and distant staging of non-small cell lung cancer. METHODS: The estimates were calculated by the epidemiological method for years 2014 to 2018. Nation-wide data were used about the incidence; data on distribution of the disease's prevalence and on the technologies' accuracy were from the literature; data regarding involved costs were taken from a micro costing study and from Brazilian Unified Health System (SUS) database. Two strategies for using PET were analyzed: the offer to all newly-diagnosed patients, and the restricted offer to the ones who had negative results in previous computed tomography (CT) exams. Univariate and extreme scenarios sensitivity analyses were conducted to evaluate the influence from sources of uncertainties in the parameters used. RESULTS: The incorporation of PET-CT in SUS would imply the need for additional resources of 158.1 BRL (98.2 USD) million for the restricted offer and 202.7 BRL (125.9 USD) million for the inclusive offer in five years, with a difference of 44.6 BRL (27.7 USD) million between the two offer strategies within that period. In absolute terms, the total budget impact from its incorporation in SUS, in five years, would be 555 BRL (345 USD) and 600 BRL (372.8 USD) million, respectively. The costs from the PET-CT procedure were the most influential parameter in the results. In the most optimistic scenario, the additional budget impact would be reduced to 86.9 BRL (54 USD) and 103.8 BRL (64.5 USD) million, considering PET-CT for negative CT and PET-CT for all, respectively. CONCLUSIONS: The incorporation of PET in the clinical staging of non-small cell lung cancer seems to be financially feasible considering the high budget of the Brazilian Ministry of Health. The potential reduction in the number of unnecessary surgeries may cause the available resources to be more efficiently allocated. PMID- 26274872 TI - Institutional and matrix support and its relationship with primary healthcare. AB - OBJECTIVE: To analyze whether the level of institutional and matrix support is associated with better certification of primary healthcare teams. METHODS: In this cross-sectional study, we evaluated two kinds of primary healthcare support 14,489 teams received institutional support and 14,306 teams received matrix support. Logistic regression models were applied. In the institutional support model, the independent variable was "level of support" (as calculated by the sum of supporting activities for both modalities). In the matrix support model, in turn, the independent variables were the supporting activities. The multivariate analysis has considered variables with p < 0.20. The model was adjusted by the Hosmer-Lemeshow test. RESULTS: The teams had institutional and matrix supporting activities (84.0% and 85.0%), respectively, with 55.0% of them performing between six and eight activities. For the institutional support, we have observed 1.96 and 3.77 chances for teams who had medium and high levels of support to have very good or good certification, respectively. For the matrix support, the chances of their having very good or good certification were 1.79 and 3.29, respectively. Regarding to the association between institutional support activities and the certification, the very good or good certification was positively associated with self-assessment (OR = 1.95), permanent education (OR = 1.43), shared evaluation (OR = 1.40), and supervision and evaluation of indicators (OR = 1.37). In regards to the matrix support, the very good or good certification was positively associated with permanent education (OR = 1.50), interventions in the territory (OR = 1.30), and discussion in the work processes (OR = 1.23). CONCLUSIONS: In Brazil, supporting activities are being incorporated in primary healthcare, and there is an association between the level of support, both matrix and institutional, and the certification result. PMID- 26274873 TI - Graphene-based nanoprobes for molecular diagnostics. AB - In recent years, graphene has received widespread attention owing to its extraordinary electrical, chemical, optical, mechanical and structural properties. Lately, considerable interest has been focused on exploring the potential applications of graphene in life sciences, particularly in disease related molecular diagnostics. In particular, the coupling of functional molecules with graphene as a nanoprobe offers an excellent platform to realize the detection of biomarkers, such as nucleic acids, proteins and other bioactive molecules, with high performance. This article reviews emerging graphene-based nanoprobes in electrical, optical and other assay methods and their application in various strategies of molecular diagnostics. In particular, this review focuses on the construction of graphene-based nanoprobes and their special advantages for the detection of various bioactive molecules. Properties of graphene-based materials and their functionalization are also comprehensively discussed in view of the development of nanoprobes. Finally, future challenges and perspectives of graphene-based nanoprobes are discussed. PMID- 26274874 TI - Neuromuscular Blockade: Using Quantitative Monitoring to Get It Just Right. PMID- 26274875 TI - Probing High-density Functional Protein Microarrays to Detect Protein-protein Interactions. AB - High-density functional protein microarrays containing ~4,200 recombinant yeast proteins are examined for kinase protein-protein interactions using an affinity purified yeast kinase fusion protein containing a V5-epitope tag for read-out. Purified kinase is obtained through culture of a yeast strain optimized for high copy protein production harboring a plasmid containing a Kinase-V5 fusion construct under a GAL inducible promoter. The yeast is grown in restrictive media with a neutral carbon source for 6 hr followed by induction with 2% galactose. Next, the culture is harvested and kinase is purified using standard affinity chromatographic techniques to obtain a highly purified protein kinase for use in the assay. The purified kinase is diluted with kinase buffer to an appropriate range for the assay and the protein microarrays are blocked prior to hybridization with the protein microarray. After the hybridization, the arrays are probed with monoclonal V5 antibody to identify proteins bound by the kinase V5 protein. Finally, the arrays are scanned using a standard microarray scanner, and data is extracted for downstream informatics analysis to determine a high confidence set of protein interactions for downstream validation in vivo. PMID- 26274876 TI - Isokinetic profile in female athletes with and without patellofemoral pain syndrome after anterior cruciate ligament reconstruction. PMID- 26274877 TI - Induction and Assessment of Ischemia-reperfusion Injury in Langendorff-perfused Rat Hearts. AB - The biochemical events surrounding ischemia reperfusion injury in the acute setting are of great importance to furthering novel treatment options for myocardial infarction and cardiac complications of thoracic surgery. The ability of certain drugs to precondition the myocardium against ischemia reperfusion injury has led to multiple clinical trials, with little success. The isolated heart model allows acute observation of the functional effects of ischemia reperfusion injury in real time, including the effects of various pharmacological interventions administered at any time-point before or within the ischemia reperfusion injury window. Since brief periods of ischemia can precondition the heart against ischemic injury, in situ aortic cannulation is performed to allow for functional assessment of non-preconditioned myocardium. A saline filled balloon is placed into the left ventricle to allow for real-time measurement of pressure generation. Ischemic injury is simulated by the cessation of perfusion buffer flow, followed by reperfusion. The duration of both ischemia and reperfusion can be modulated to examine biochemical events at any given time point. Although the Langendorff isolated heart model does not allow for the consideration of systemic events affecting ischemia and reperfusion, it is an excellent model for the examination of acute functional and biochemical events within the window of ischemia reperfusion injury as well as the effect of pharmacological intervention on cardiac pre- and postconditioning. The goal of this protocol is to demonstrate how to perform in situ aortic cannulation and heart excision followed by ischemia/reperfusion injury in the Langendorff model. PMID- 26274879 TI - Shared medical appointments: An innovative approach to patient care. AB - This article provides an overview of shared medical appointments, an innovative approach to managing patients with chronic conditions. The Diabetes Shared Medical Appointment of the Veterans Affairs Loma Linda Healthcare System, conducted by an interprofessional team and led by a nurse practitioner, is described. PMID- 26274878 TI - Isolation and Characterization of Satellite Cells from Rat Head Branchiomeric Muscles. AB - Fibrosis and defective muscle regeneration can hamper the functional recovery of the soft palate muscles after cleft palate repair. This causes persistent problems in speech, swallowing, and sucking. In vitro culture systems that allow the study of satellite cells (myogenic stem cells) from head muscles are crucial to develop new therapies based on tissue engineering to promote muscle regeneration after surgery. These systems will offer new perspectives for the treatment of cleft palate patients. A protocol for the isolation, culture and differentiation of satellite cells from head muscles is presented. The isolation is based on enzymatic digestion and trituration to release the satellite cells. In addition, this protocol comprises an innovative method using extracellular matrix gel coatings of millimeter size, which requires only low numbers of satellite cells for differentiation assays. PMID- 26274880 TI - Humans versus artificial intelligence. PMID- 26274881 TI - H.R.2. fixes more than Medicare reimbursement rates for NPs. PMID- 26274882 TI - Sofosbuvir (Sovaldi) for hepatitis C virus. PMID- 26274885 TI - Patients' knowledge of pain agreements. AB - This study was conducted to determine patients' knowledge of pain agreements. METHODS: Descriptive quantitative survey design. A 28-item questionnaire regarding patients' knowledge of pain agreements was distributed to pain management office patients. RESULTS: Participants (N = 76) scored 30%-100% (mean 80%) on knowledge of 10 pain agreement items. CONCLUSIONS: Patients demonstrated moderate knowledge of terms. PMID- 26274886 TI - Ovarian cancer: Ensuring early diagnosis. AB - Ovarian cancer is the most fatal of all gynecologic malignancies. Despite the lack of a recommended screening test for ovarian cancer, NPs can identify risk factors, ensure patients are aware of subtle symptoms, and provide adequate testing and analysis of results. PMID- 26274888 TI - Preparation of Mica and Silicon Substrates for DNA Origami Analysis and Experimentation. AB - The designed nature and controlled, one-pot synthesis of DNA origami provides exciting opportunities in many fields, particularly nanoelectronics. Many of these applications require interaction with and adhesion of DNA nanostructures to a substrate. Due to its atomically flat and easily cleaned nature, mica has been the substrate of choice for DNA origami experiments. However, the practical applications of mica are relatively limited compared to those of semiconductor substrates. For this reason, a straightforward, stable, and repeatable process for DNA origami adhesion on derivatized silicon oxide is presented here. To promote the adhesion of DNA nanostructures to silicon oxide surface, a self assembled monolayer of 3-aminopropyltriethoxysilane (APTES) is deposited from an aqueous solution that is compatible with many photoresists. The substrate must be cleaned of all organic and metal contaminants using Radio Corporation of America (RCA) cleaning processes and the native oxide layer must be etched to ensure a flat, functionalizable surface. Cleanrooms are equipped with facilities for silicon cleaning, however many components of DNA origami buffers and solutions are often not allowed in them due to contamination concerns. This manuscript describes the set-up and protocol for in-lab, small-scale silicon cleaning for researchers who do not have access to a cleanroom or would like to incorporate processes that could cause contamination of a cleanroom CMOS clean bench. Additionally, variables for regulating coverage are discussed and how to recognize and avoid common sample preparation problems is described. PMID- 26274889 TI - Use of Chironomidae (Diptera) Surface-Floating Pupal Exuviae as a Rapid Bioassessment Protocol for Water Bodies. AB - Rapid bioassessment protocols using benthic macroinvertebrate assemblages have been successfully used to assess human impacts on water quality. Unfortunately, traditional benthic larval sampling methods, such as the dip-net, can be time consuming and expensive. An alternative protocol involves collection of Chironomidae surface-floating pupal exuviae (SFPE). Chironomidae is a species rich family of flies (Diptera) whose immature stages typically occur in aquatic habitats. Adult chironomids emerge from the water, leaving their pupal skins, or exuviae, floating on the water's surface. Exuviae often accumulate along banks or behind obstructions by action of the wind or water current, where they can be collected to assess chironomid diversity and richness. Chironomids can be used as important biological indicators, since some species are more tolerant to pollution than others. Therefore, the relative abundance and species composition of collected SFPE reflect changes in water quality. Here, methods associated with field collection, laboratory processing, slide mounting, and identification of chironomid SFPE are described in detail. Advantages of the SFPE method include minimal disturbance at a sampling area, efficient and economical sample collection and laboratory processing, ease of identification, applicability in nearly all aquatic environments, and a potentially more sensitive measure of ecosystem stress. Limitations include the inability to determine larval microhabitat use and inability to identify pupal exuviae to species if they have not been associated with adult males. PMID- 26274890 TI - Cycloalkene Carbonitriles in Rhodium-Catalyzed 1,4-Addition and Formal Synthesis of Vabicaserin. AB - Cycloalkenes with exocyclic acceptor substituents still remain challenging substrates for enantioselective rhodium-catalyzed 1,4-addition. Cycloalkene carbonitriles and carboxylates have been investigated, and a highly diastereo- and enantioselective protocol for 1,4-addition to cyclopentene and cycloheptene carbonitrile has been developed. This new asymmetric transformation was subsequently applied in the asymmetric formal synthesis of the drug candidate Vabicaserin. PMID- 26274891 TI - Repeated sprint ability related to recovery time in young soccer players. AB - This study aimed to describe the influence of recovery duration during a repeated sprint ability (RSA) test (6 * 40 m) by investigating a number of variables, such as general performance, metabolic demand, and muscular stretch-shortening performance. Seventeen male soccer outfield players (16 +/- 0 years, 66 +/- 10 kg) performed three field shuttle-running tests with 15, 20, and 25-sec recoveries. In addition to specific shuttle test's variables, blood lactate concentration and vertical jump height were assessed. Resulting measures were highly reliable (intra-class correlation coefficient up to 0.86). 25-sec recovery improved test performance (-3% total time from 15-sec to 25-sec recovery), vertical jump height (+7% post-test height from 15-sec to 25-sec recovery), and decreased blood lactate accumulation (-33% post-test from 15-sec to 25-sec recovery). Study findings suggest that metabolic acidosis plays a role in worsening performance and fatigue development during the shuttle test. A 25-sec recovery duration maximized performance, containing metabolic-anaerobic power involvement and muscular stretch-shortening performance deterioration during a RSA test. PMID- 26274892 TI - Effect of rehabilitation protocols on muscle function and morphology following hindlimb disuse in weanling rats. AB - BACKGROUND: Primary or secondary disorders in developing skeletal muscles are prevalent in physical therapy practice. Assessment of gait functional changes and morphological aspects of hindlimb muscles of weanling rats have not been reported simultaneously in the literature. Rehabilitation by active (eccentric training) and passive (stretching) exercises after hypomobility needs to be investigated. METHODS: After ten days of immobilisation in a plantar flexion-shortened position, animals underwent eccentric training on treadmills, intermittent (a single series of ten exercises of 30 seconds each, with a 30-s interval) or continuous stretching protocols for 40 minutes, or had free cage activity for three days. Analysis of gait variables and muscle morphology (immunohistochemical staining of soleus and plantar muscles for fibronectin and types I and III collagen and immunofluorescence staining for dystrophin, laminin, Pax-7, and CD68) were performed. RESULTS: On the third day, the rehabilitated animals touched the ground surface with their toes, except for the group undergoing continuous stretching. The total amount of extracellular macrophages was higher in the rehabilitated animals. The number of satellite cells was not significantly different between groups. CONCLUSION: Three days of active training (eccentric exercise) showed greater effectiveness compared to the other rehabilitation programs. Weanling rats seem to respond differently to external stimuli such as disuse and remobilisation. PMID- 26274894 TI - Portable SERS-enabled micropipettes for microarea sampling and reliably quantitative detection of surface organic residues. AB - We report the first microsampling device for reliably quantitative, label-free and separation-free detection of multicomponents of surface organic residues (SORs) by means of a quality controllable surface-enhanced Raman scattering (SERS)-enabled micropipette. The micropipette is comprised of a drawn glass capillary with a tiny orifice (~50 MUm) at the distal tip, where the specially designed nanorattles (NRs) are compactly coated on the inner wall surface. SERS signals of 4-mercapto benzoic acid (MBA) anchored inside the internal gap of NRs could be used to evaluate and control the quality of micropipettes and, therefore, allow us to overcome the limitations of a reliably quantitative SERS assay using traditional substrates without an internal standard. By dropping a trace extraction agent on targeting SORs located on a narrow surface, the capillary and SERS functionalities of these micropipettes allow on-site microsampling via capillary action and subsequent multiplex distinction/detection due to their molecularly narrow Raman peaks. For example, 8 nM thiram (TMTD), 8 nM malachite green (MG), and 1.5 MUM (400 ppb) methyl parathion (MPT) on pepper and cucumber peels have been simultaneously detected in a wide detection range. The portable SERS-enabled device could potentially be facilely incorporated with liquid-liquid or solid phase micro-extracting devices for a broader range of applications in rapid and field analysis of food/public/environment security related SORs. PMID- 26274893 TI - Deletion of the BMP receptor BMPR1a impairs mammary tumor formation and metastasis. AB - Bone Morphogenetic Proteins (BMPs) are secreted cytokines/growth factors belonging to the Transforming Growth Factor beta (TGFbeta) family. BMP ligands have been shown to be overexpressed in human breast cancers. Normal and cancerous breast tissue display active BMP signaling as indicated by phosphorylated Smads 1, 5 and 9. We combined mice expressing the MMTV.PyMT oncogene with mice having conditional knockout (cKO) of BMP receptor type 1a (BMPR1a) using whey acidic protein (WAP)-Cre and found this deletion resulted in delayed tumor onset and significantly extended survival. Immunofluorescence staining revealed that cKO tumors co-expressed Keratin 5 and mesenchymal cell markers such as Vimentin. This indicates that epithelial-to-mesenchymal (EMT)-like transitions occurred in cKO tumors. We performed microarray analysis on these tumors and found changes that support EMT-like changes. We established primary tumor cell lines and found that BMPR1a cKO had slower growth in vitro and in vivo upon implantation. cKO tumor cells had reduced migration in vitro. We analyzed human databases from TCGA and survival data from microarrays to confirm BMPR1a tumor promoting functions, and found that high BMPR1a gene expression correlates with decreased survival regardless of molecular breast cancer subtype. In conclusion, the data indicate that BMP signaling through BMPR1a functions as a tumor promoter. PMID- 26274895 TI - SNARC (spatial-numerical association of response codes) meets SPARC (spatial pitch association of response codes): Automaticity and interdependency in compatibility effects. AB - Concepts, including the mental number line, or addressing pitch as high and low, suggest that the spatial-numerical and spatial-pitch association of response codes (SNARC and SPARC) effects are domain-specific and thus independent. Alternatively, there may be dependencies between these effects, because they share common automatic or controlled decision mechanisms. In two experiments, participants were presented with spoken numbers in different pitches; their numerical value, pitch, and response compatibility were varied systematically. This allowed us to study SNARC and SPARC effects in a factorial design (see also Fischer, Riello, Giordano, & Rusconi, 2013 ). Participants judged the stimuli on numerical magnitude, pitch, or parity (odd-even). In all tasks, the SNARC and SPARC effects had superadditive interactions. These were interpreted as both effects sharing a common mechanism. The task variation probes the mechanism: In the magnitude judgement task, numerical magnitude was explicit, whereas pitch was implicit; in the pitch judgement task, it was vice versa. In the parity judgement task, both dimensions were implicit. Regardless of whether they were implicit or explicit, both SNARC and SPARC effects occurred in all tasks. We concluded that by not requiring focal attention the common mechanism operates automatically. PMID- 26274896 TI - Concise Redox Deracemization of Secondary and Tertiary Amines with a Tetrahydroisoquinoline Core via a Nonenzymatic Process. AB - A concise deracemization of racemic secondary and tertiary amines with a tetrahydroisoquinoline core has been successfully realized by orchestrating a redox process consisted of N-bromosuccinimide oxidation and iridum-catalyzed asymmetric hydrogenation. This compatible redox combination enables one-pot, single-operation deracemization to generate chiral 1-substituted 1,2,3,4 tetrahydroisoquinolines with up to 98% ee in 93% yield, offering a simple and scalable synthetic technique for chiral amines directly from racemic starting materials. PMID- 26274900 TI - Transferable Anisotropic United-Atom Force Field Based on the Mie Potential for Phase Equilibrium Calculations: n-Alkanes and n-Olefins. AB - A new transferable force field parametrization for n-alkanes and n-olefins is proposed in this work. A united-atom approach is taken, where hydrogen atoms are lumped with neighboring atoms to single interaction sites. A comprehensive study is conducted for alkanes, optimizing van der Waals force field parameters in 6 dimensions. A Mie n-6 potential is considered for the van der Waals interaction, where for n-alkanes we simultaneously optimize the energy parameters epsilonCH3 and epsilonCH2 as well as the size parameters sigmaCH3 and sigmaCH2 of the CH3(sp(3)) and CH2(sp(3)) groups. Further, the repulsive exponent n of the Mie n 6 potential is varied. Moreover, we investigate the bond length toward the terminal CH3 group as a degree of freedom. According to the AUA (anisotropic united-atom) force field, the bond length between the terminal CH3 group and the neighboring interaction site should be increased by Deltal compared with the carbon-carbon distance in order to better account for the hydrogen atoms. The parameter Deltal is considered as a degree of freedom. The intramolecular force field parametrization is taken from existing force fields. A single objective function for the optimization is defined as squared relative deviations in vapor pressure and in liquid density of propane, n-butane, n-hexane, and n-octane. A similar study is also done for olefins, where the objective function includes 1 butene, 1-hexene, 1-octene, cis-2-pentene, and trans-2-pentene. Molecular simulations are performed in the grand canonical ensemble with transition-matrix sampling where the phase equilibrium properties are obtained with the histogram reweighting technique. The 6-dimensional optimization of strongly correlated parameters is possible, because the analytic PC-SAFT equation of state is used to locally correlate simulation results. The procedure is iterative but leads to very efficient convergence. An implementation is proposed, where the converged result is not affected (disturbed) by the analytic equation of state. The resulting transferable anisotropic Mie-potential (TAMie) force field shows average relative deviations in vapor pressure of 1.1% and in liquid density of 0.9% for alkanes, and 2% and 1.5% for olefins, respectively, in a wide range of (reduced) temperature, Tr = 0.55-0.97. For substances that were not members of the objective function, the TAMie force field enables predictions of phase equilibrium properties with good accuracy. PMID- 26274897 TI - What role does transactional sex play in the HIV/STI and reproductive health risk behaviour among high-tier entertainment centre workers in China? AB - China's rapid economic growth over the last three decades has led to increased population wealth and the proliferation of entertainment centres where people can conduct business, relax and meet new people. Little is known about the sexual risk behaviours of employees at high-tier entertainment centres. This paper addresses this gap in knowledge by comparing HIV risk perception and sexual and reproductive health behaviours among female and male employees at three high-tier entertainment centres in two cities in China, comparing those who report a history of transactional sex to those who do not. In both cities, participants who reported a history of transactional sex were more likely than those without a history of transactional sex to report multiple sexual partnerships, more lifetime sexual partners, a history of sexually transmitted infections (STIs), having anal sex and/or recent abortions, and were more likely to perceive themselves to be at risk for STIs/HIV. However, risk behaviour was also high among those with no history of transactional sex. These findings highlight the need for targeted sexual and reproductive health initiatives for employees in these work settings. PMID- 26274901 TI - Asymmetric Dental Development Investigated by Cone-Beam Computed Tomography in Patients With Unilateral Cleft Lip and Alveolus. AB - OBJECTIVE: To investigate a possible delay in dental development of cleft-side teeth compared with the contralateral teeth in patients with unilateral cleft lip and alveolus with or without cleft palate (UCLA +/- CP) and to correlate this delay to developmental stages of the corresponding teeth. DESIGN: Cross-sectional study. SETTING: Cleft Lip and Palate Care Center of Shanghai Ninth People's Hospital, Shanghai, China. PATIENTS: Forty Chinese patients with UCLA +/- CP. MAIN OUTCOME MEASURE: Crown height (CH), root length (RL), and full length (FL) of permanent incisors, canines, premolars, and first molars were measured using cone-beam computed tomography and compared between cleft and noncleft sides. Discrepancies in tooth length between sides during different developmental stages of delayed teeth were also compared. RESULTS: There were no statistically significant differences in tooth length between sides in the mandible, except for RL of lateral incisors and RL and FL of the second premolars. In the maxilla, CH, RL and FL of cleft-side incisors, as well as RL and FL of cleft-side canines and first premolars, were all significantly shorter than those on the noncleft side (P < .05). The lateral incisors showed the highest reductions in RL and FL (47% and 29%). Moreover, reduction of RL of cleft-side maxillary central incisors was most evident in the early developmental stage (23%) and decreased with dental maturation (5%). CONCLUSIONS: Asymmetric dental development was presented in both jaws but mainly in maxillary anterior region. The RL deficiency of cleft-side central incisors differed at different developmental stages. PMID- 26274902 TI - Cognitive neuroscience of synesthesia: Introduction to the special issue. AB - This Special Issue of Cognitive Neuroscience showcases the latest theories and findings in research on synesthesia. The various contributions are discussed in relation to three broad themes: Models and neural mechanisms; new types of synesthesia; and cognitive profile and demographic characteristics. PMID- 26274903 TI - Grading keratinocyte atypia in actinic keratosis: a correlation of reflectance confocal microscopy and histopathology. AB - BACKGROUND: Actinic Keratosis (AK) is the clinical manifestation of cutaneous dysplasia of epidermal keratinocytes, with progressive trend towards squamous cell carcinoma. OBJECTIVE: To evaluate the strength of the correlation between keratinocyte atypia, as detected by Reflectance Confocal Microscopy (RCM) and histopathology, and to develop a more objective atypia grading scale for RCM quantification, through a discrete ranking. METHODS: A total of 48 AKs and two control areas (photodamaged and non-photodamaged skin) were selected for this study. All these areas were documented by RCM and biopsied for histopathology. One representative image of the epidermis was selected for RCM and for histopathology and used for side-by-side comparison with purpose written software. The assessor chose which of two images displayed more keratinocyte atypia, and an ordered list from the image showing the least to the most keratinocyte atypia was generated. Three evaluations were obtained for RCM and two for histopathology. RESULTS: Good interobserver correlation was obtained for RCM and histopathology grading, with high concordance between RCM and histopathology grading. CONCLUSIONS: Expert rater scan consistently distinguish different grades of cytological atypia. Non-invasive RCM data from in vivo imaging can be graded for keratinocyte atypia, comparable to histopathological grading. PMID- 26274904 TI - Comparison of a predictive algorithm with receptionist triage for priority public dental care. AB - OBJECTIVE: To determine the clinical validity and accuracy of an empirically derived triage model when compared with traditional priority assessment by receptionists. BACKGROUND: The use of predictive models to support evidence-based delivery of health care is increasing. Predictive models assist in predicting priority of need or treatment planning for patients and facilitate transparent and consistent decision-making. A predictive model for determining priority of need for dental care was evaluated against a reference standard dentist assessment and traditional receptionist assessment. METHODS: We sampled 310 patients seeking dental care. Participants were selected from people requesting care at two community dental clinics and who agreed to answer eight questions. Receptionists recorded their judgements of participant priority into three categories: care needed <48 h, 2-7 days or 8+ days. The 'reference standard' priority was determined by dental officers using the same categories. Model coefficients generated a predicted probability of requiring care. Sensitivity (Se), specificity (Sp), and predictive (PPV and NPV) and area under the curve (AUC) values were computed for two thresholds, <48 h versus 2+ days and <2-7 days versus 8+ days. RESULTS: At <48-h threshold, the model PPV was higher and NPV lower than receptionists in predicting patients not needing care. At the 2- to 7 day threshold, the model also performed better than receptionists in predicting those needing care for 2-7 days. AUC statistics show the model performed better than the traditional receptionist method. CONCLUSIONS: The predictive model outperformed traditional receptionist screening in predicting priority of care. PMID- 26274905 TI - Ribavirin Contributes to Hepatitis C Virus Suppression by Augmenting pDC Activation and Type 1 IFN Production. AB - Ribavirin is used as a component of combination therapies for the treatment of chronic hepatitis C virus (HCV) infection together with pegylated interferon and/or direct-acting antiviral drugs. Its mechanism of action, however, is not clear. Direct antiviral activity and immunomodulatory functions have been implicated. Plasmacytoid dendritic cells (pDCs) are the principal source of type 1 interferon during viral infection. The interaction of pDCs with HCV-infected hepatocytes is the subject of intense recent investigation, but the effect of ribavirin on pDC activation has not been evaluated. In this study we showed that ribavirin augments toll-like receptors 7 and 9-mediated IFNalpha/beta expression from pDCs and up-regulated numerous interferon-stimulated genes. Using the H77S.3 HCV infection and replication system, we showed that ribavirin enhanced the ability of activated pDCs to inhibit HCV replication, correlated with elevated induction of IFNalpha. Our findings provide novel evidence that ribavirin contributes to HCV inhibition by augmenting pDCs-derived type 1 IFN production. PMID- 26274906 TI - Free Fatty Acid Effects on the Atrial Myocardium: Membrane Ionic Currents Are Remodeled by the Disruption of T-Tubular Architecture. AB - BACKGROUND: Epicardial adiposity and plasma levels of free fatty acids (FFAs) are elevated in atrial fibrillation, heart failure and obesity, with potentially detrimental effects on myocardial function. As major components of epicardial fat, FFAs may be abnormally regulated, with a potential to detrimentally modulate electro-mechanical function. The cellular mechanisms underlying such effects of FFAs are unknown. OBJECTIVE: To determine the mechanisms underlying electrophysiological effects of palmitic (PA), stearic (SA) and oleic (OA) FFAs on sheep atrial myocytes. METHODS: We used electrophysiological techniques, numerical simulations, biochemistry and optical imaging to examine the effects of acutely (<= 15 min), short-term (4-6 hour) or 24-hour application of individual FFAs (10 MUM) on isolated ovine left atrial myocytes (LAMs). RESULTS: Acute and short-term incubation in FFAs resulted in no differences in passive or active properties of isolated left atrial myocytes (LAMs). 24-hour application had differential effects depending on the FFA. PA did not affect cellular passive properties but shortened (p<0.05) action potential duration at 30% repolarization (APD30). APD50 and APD80 were unchanged. SA had no effect on resting membrane potential but reduced membrane capacitance by 15% (p<0.05), and abbreviated APD at all values measured (p<=0.001). OA did not significantly affect passive or active properties of LAMs. Measurement of the major voltage-gated ion channels in SA treated LAMs showed a ~60% reduction (p<0.01) of the L-type calcium current (ICa-L) and ~30% reduction (p<0.05) in the transient outward potassium current (ITO). A human atrial cell model recapitulated SA effects on APD. Optical imaging showed that SA incubated for 24 hours altered t-tubular structure in isolated cells (p<0.0001). CONCLUSIONS: SA disrupts t-tubular architecture and remodels properties of membrane ionic currents in sheep atrial myocytes, with potential implications in arrhythmogenesis. PMID- 26274907 TI - The Imidazoquinoline Toll-Like Receptor-7/8 Agonist Hybrid-2 Potently Induces Cytokine Production by Human Newborn and Adult Leukocytes. AB - BACKGROUND: Newborns and young infants are at higher risk for infections than adults, and manifest suboptimal vaccine responses, motivating a search for novel immunomodulators and/or vaccine adjuvants effective in early life. In contrast to most TLR agonists (TLRA), TLR8 agonists such as imidazoquinolines (IMQs) induce adult-level Th1-polarizing cytokine production from human neonatal cord blood monocytes and are candidate early life adjuvants. We assessed whether TLR8 activating IMQ congeners may differ in potency and efficacy in inducing neonatal cytokine production in vitro, comparing the novel TLR7/8-activating IMQ analogues Hybrid-2, Meta-amine, and Para-amine to the benchmark IMQ resiquimod (R848). METHODS: TLRA-induced NF-kappaB activation was measured in TLR-transfected HEK cells. Cytokine production in human newborn cord and adult peripheral blood and in monocyte-derived dendritic cell cultures were measured by ELISA and multiplex assays. X-ray crystallography characterized the interaction of human TLR8 with Hybrid-2. RESULTS: Hybrid-2 selectively activated both TLR7 and 8 and was more potent than R848 in inducing adult-like levels of TNF-alpha, and IL-1beta. Consistent with its relatively high in vitro activity, crystallographic studies suggest that absence in Hybrid-2 of an ether oxygen of the C2-ethoxymethyl substituent, which can engage in unfavorable electrostatic and/or dipolar interactions with the carbonyl oxygen of Gly572 in human TLR8, may confer greater efficacy and potency compared to R848. CONCLUSIONS: Hybrid-2 is a selective and potent TLR7/8 agonist that is a candidate adjuvant for early life immunization. PMID- 26274908 TI - The mediating role of individual resilience resources in stigma-health relationship among people living with HIV in Guangxi, China. AB - Despite the vigorous global efforts to reduce stigma, HIV-related stigma continues to undermine the health status of people living with HIV (PLHIV). Internalized HIV stigma may cause stress adversely affecting the health of PLHIV. Resilience is the process of an effective coping and positive adaption in the face of adversities. To date, limited data are available on the mediating role of resilience in the relationship of internalized HIV stigma and health status among PLHIV in China. A cross-sectional survey was conducted among 2987 PLHIV in Guangxi Autonomous Region (Guangxi) in China. A mediation analysis was employed and Sobel test was used to test the mediation effect of individual resilience. Of the 2987 PLHIV, 62.8% were men. The mean age of the sample was 42.5 years (SD = 12.8). Over 57.7% of PLHIV reported their overall health status being poor. About 72% of PLHIV reported experiencing internalized HIV stigma. Internalized HIV stigma had a negative direct effect on self-rated health status (p < .001). Individual resilience resources mediated the relationship between internalized HIV stigma and self-rated health status (p < .001). Sobel test confirmed the mediation effect of resilience (z = -8.359, SE = 0.003, p < .001). Resilience as a protective factor might buffer the effect of internalized HIV stigma on health status. Multilevel interventions are needed to foster resilience of PLHIV in order to mitigate the negative impact of HIV stigma and to improve the overall health status of PLHIV. PMID- 26274909 TI - N-Acetyl Cysteine (NAC)-Directed Detoxification of Methacryloxylethyl Cetyl Ammonium Chloride (DMAE-CB). AB - Methacryloxylethyl cetyl ammonium chloride (DMAE-CB) is a polymerizable antibacterial monomer and has been proved as an effective strategy to achieve bioactive bonding with reliable bacterial inhibitory effects. However, the toxicity of DMAE-CB may hamper its wide application in clinical situations. Thus, this study was designed to investigate the toxicity of DMAE-CB and explore the possible protective effects of N-acetyl cysteine (NAC). High performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) analysis showed that chemical binding of NAC and DMAE-CB occurred in a time dependent manner. Pre-incubation of fourty-eight hours is required for adequate reaction between DMAE-CB and NAC. DMAE-CB reduced human dental pulp cells (hDPCs) viability in a dose-dependent manner. The toxic effects of DMAE-CB were accompanied by increased reactive oxygen species (ROS) level and reduced glutathione (GSH) content. NAC alleviated DMAE-CB-induced oxidative stress. Annexin V/ Propidium Iodide (PI) staining and Hoechst 33342 staining indicated that DMAE-CB induced apoptosis. Collapsed mitochondrial membrane potential (MMP) and activation of caspase-3 were also observed after DMAE-CB treatment. NAC rescued hDPCs from DMAE-CB-induced apoptosis, accompanied by lower level of MMP loss and caspase-3 activity. This study assists to elucidate the mechanism underlying the cytotoxic effects of DMAE-CB and provides theoretical supports for the searching of effective strategies to reduce toxicity of quaternary ammonium dental monomers. PMID- 26274910 TI - The Impact of Technology-Based Interventions on Informal Caregivers of Stroke Survivors: A Systematic Review. AB - OBJECTIVE: This article is a systematic review of the impact of technology-based intervention on outcomes related to care providers for those who survived a stroke. MATERIALS AND METHODS: Literature was identified in the PubMed, PsycINFO, Scopus, and Cochrane databases for evidence on technology-based interventions for stroke survivors' caregivers. The search was restricted for all English-language articles from 1970 to February 2015 that implied technology-based interventions. This review included studies that measured the impact of these types of approaches on one or more of the following: depression and any of the following problem-solving ability, burden, health status, social support, preparedness, and healthcare utilization by care recipient-as secondary outcomes. Telephone or face to-face counseling sessions were not of interest for this review. The search strategy yielded five studies that met inclusion criteria: two randomized clinical trials and three pilot/preliminary studies, with diverse approaches and designs. RESULTS: Four studies have assessed the primary outcome, two of which reported significant decreases in caregivers' depressive symptoms. Two studies had measured each of the following outcomes-burden, problem-solving ability, health status, and social support-and they revealed no significant differences following the intervention. Only one study assessed caregivers' preparedness and showed improved posttest scores. Healthcare services use by the care recipient was assessed by one study, and the results indicated significant reduction in emergency department visits and hospital re-admissions. CONCLUSIONS: Despite various study designs and small sample sizes, available data suggest that an intervention that incorporates a theoretical-based model and is designed to target caregivers as early as possible is a promising strategy. Furthermore, there is a need to incorporate a cost-benefit analysis in future studies. PMID- 26274911 TI - A fragmentation study on four C19-diterpenoid alkaloids by electrospray ionization ion-trap time-of-flight tandem mass spectrometry. AB - High-resolution electrospray ionization ion-trap time-of-flight tandem mass spectrometry (HR-ESI-IT-TOF-MS(n)) in positive-ion mode was used to determine the accurate masses and fragmentation pathways of four C(19)-diterpenoid alkaloids, aconitine (1), yunnaconitine (2), crassicauline A (3), and benzoylmesaconine (4). The [M+H](+) ions of compounds 1-4 were readily observed in conventional single stage mass spectrometry. Based on the MS(1-6) analyses, detailed fragmentation rules of the four compounds were proposed. The neutral losses of AcOH, MeOH, H(2)O, CO, C(2)H(4), PhCOOH and p-OMePhCOOH segments were the characteristic eliminations from the precursor ions due to the presence of acetyl, methoxyl, hydroxyl, N-ethyl, benzoyl and p-methoxyl-benzoyl units in the structures. Benefited from the high resolution of the mass analyzer, the loss of 28 Da corresponding to CO or CH(4) segment in product ions was unambiguously distinguished. The losing sequence of the main substituent groups was summarized as: C(8)-acetyl>C(16)-methotyl>C(15)-hydroxyl>C(6)-methoxyl>C(1)-methoxyl/C(3) hydroxyl>C(18)-methoxyl>>C(13)-hydroxyl. The sequential loss of (16)-methoxyl moiety and CO (generating from enol-ketone tautomerism) groups could be recognized as the characteristic eliminations for the compounds with C(16) methoxyl and C(15)-hydroxyl groups simultaneously. The application of HR-ESI-IT TOF-MS(n) technique to investigate the fragmentation of C(19)-diterpenoid alkaloids provided useful information to understand their fragmentation behaviors. PMID- 26274913 TI - Molecular Dynamics Simulation Study of Skin Lipids: Effects of the Molar Ratio of Individual Components over a Wide Temperature Range. AB - Atomistic molecular dynamics (MD) simulations were employed to systematically investigate the effects of the molar ratio of the individual components cholesterol (CHOL), free fatty acid (FFA), and ceramides (CER) on the properties of the skin lipid bilayer over a wide temperature range (300-400 K). Several independent simulations were performed for bilayers comprised of only CER, CHOL, or FFA molecules as well as those made up of a mixture of CER:CHOL:FFA molecules in different molar ratios. It was found that CHOL increases the stability of the bilayer, since the mixed (CER:CHOL:FFA) 1:1:0, 1:1:1, and 2:2:1 bilayers remained stable until 400 K while the pure ceramide bilayer disintegrated around ~390 K. It was also observed that CHOL reduces the volume spanned by ceramide molecules, thereby leading to a higher area per CER and FFA molecule in the mixed bilayer system. The CHOL molecule provided more rigidity to the mixed bilayer and led to a more ordered phase at elevated temperatures. The CHOL molecule provided fluidity to the bilayer below the phase transition temperature of CER and kept the bilayer rigid above the phase transition temperature. The FFA interdigitizes with CER molecules and increases the thickness of the bilayer, while rigid CHOL decreases the bilayer thickness. The presence of CHOL increases the compressibility of the bilayer which is responsible for the high barrier function of skin. The CER molecule forms inter- and intramolecular hydrogen bonds, while CHOL only forms intermolecular hydrogen bonds. PMID- 26274914 TI - Adaptive Phase-Field Modeling of Anisotropic Wetting with Line Tension at the Triple Junction. AB - Line tension could affect the contact angle at triple junction, especially in micro- to nanoscale wetting. We have developed an adaptive phase-field model to consider the line tension quantitatively. This model is coupled to the smoothed boundary method for treating the contact line with the solid phase, while the volume constraint is imposed. Our calculated contact angles are in good agreement with the modified Young's equation. Further examples are illustrated for the anisotropic wetting on hydrophilic/hydrophobic stripes and rectangular grooves. PMID- 26274912 TI - Comparative Efficacy and Safety of Different Antiplatelet Agents for Prevention of Major Cardiovascular Events and Leg Amputations in Patients with Peripheral Arterial Disease: A Systematic Review and Network Meta-Analysis. AB - There is a lack of consensus regarding which type of antiplatelet agent should be used in patients with peripheral arterial disease (PAD) and little is known on the advantages and disadvantages of dual antiplatelet therapy. We conducted a systematic review and network meta-analysis of available randomized controlled trials (RCT) comparing different antiplatelet drugs (Aspirin, Ticlopidine, Clopidogrel, Ticagrelor, Cilostazol, Picotamide and Vorapaxar as monotherapies or in combination with aspirin) in PAD patients (PROSPERO public database; CRD42014010299).We collated evidence from previous relevant meta-analyses and searched online databases. Primary efficacy endpoints were: (1) the composite rate of major adverse cardiovascular events (MACE; including vascular deaths, non fatal myocardial infarction and non-fatal stroke), and (2) the rate of major leg amputations. The primary safety endpoint was the rate of severe bleeding events. Bayesian models were employed for multiple treatment comparisons and risk stratified hierarchies of comparative efficacy were produced to aid medical decision making. Number-Needed-to-Treat (NNT) and Number-Needed-to-Harm (NNH) are reported in case of significant results. We analyzed 49 RCTs comprising 34,518 patients with 88,358 person-years of follow-up with placebo as reference treatment. Aspirin, Cilostazol, Vorapaxar and Picotamide were ineffective in reducing MACE. A significant MACE reduction was noted with Ticagrelor plus aspirin (RR: 0.67; 95%CrI: 0.46-0.96, NNT = 66), Clopidogrel (RR: 0.72; 95%CrI: 0.58-0.91, NNT = 80), Ticlopidine (RR: 0.75; 95%CrI: 0.58-0.96, NNT = 87), and Clopidogrel plus aspirin (RR: 0.78; 95%CrI: 0.61-0.99, NNT = 98). Dual antiplatelet therapy with Clopidogrel plus aspirin significantly reduced major amputations following leg revascularization (RR: 0.68; 95%CrI: 0.46-0.99 compared to aspirin, NNT = 94). The risk of severe bleeding was significantly higher with Ticlopidine (RR: 5.03; 95%CrI: 1.23-39.6, NNH = 25), Vorapaxar (RR: 1.80; 95%CrI: 1.22-2.69, NNH = 130), and Clopidogrel plus aspirin (RR: 1.48; 95%CrI: 1.05-2.10, NNH = 215). Clopidogrel monotherapy showed the most favourable benefit-harm profile (79% cumulative rank probability best and 77% cumulative rank probability safest). In conclusion, Clopidogrel should be the indicated antiplatelet agent in PAD patients. Dual antiplatelet therapy with aspirin and Clopidogrel can reduce the rate of major leg amputations following revascularization, but carries a slightly higher risk of severe bleeding. PMID- 26274915 TI - Production of Hydroxyl Radical via the Activation of Hydrogen Peroxide by Hydroxylamine. AB - The production of the hydroxyl radical (HO.) is important in environmental chemistry. This study reports a new source of HO. generated solely from hydrogen peroxide (H2O2) activated by hydroxylamine (HA). Electron paramagnetic resonance analysis and the oxidation of a HO. probe, benzoic acid, were used to confirm the production of HO.. The production of HO. increased with increasing concentrations of either HA or H2O2 as well as decreasing pH. The second-order rate constant for the reaction was (2.2 +/- 0.2) * 10(-4) M(-1) s(-1). HO. was probably produced in two steps: the activation of H2O2 by protonated HA and then reaction between the H2O2 and the intermediate protonated aminoxyl radical generated in the first step. Such a two-step oxidation can possibly be ascribed to the ionizable hydroxyl moiety in the molecular structure of HA, as is suggested by comparing the reactivity of a series of HA derivatives in HO. production. The results shed light on a previously unknown source of HO. formation, which broadens the understanding of its role in environmental processes. PMID- 26274917 TI - Diagnosis of iron-deficient states. AB - The diagnosis of iron deficiency anemia is typically straightforward, especially when classic biochemical and hematological changes are present in a subject at risk. It can be challenging in the presence of diseases or when it is due to inherited defects of iron metabolism. The identification of iron deficiency prior to anemia development is also difficult. New hematological parameters such as reticulocyte Hb content have expanded the classic ones such as MCV, MCH and MCHC. A variety of hematology analyzers now provide novel parameters to assess cellular hypochromia and microcytosis in both reticulocytes and mature red blood cells. The repertoire of biochemical markers has also been expanded, with iron, transferrin and ferritin being supplemented by circulating transferrin receptor and hepcidin. Molecular identification of functional variants of key iron metabolism determinants has provided explanations for the heritability of some iron metabolism biomarkers. Genetic defects in some of these molecules are responsible for hereditary microcytic anemias, also called atypical microcytic anemias. In this review, we examine the most significant hematological and biochemical markers for iron metabolism, as well as relevant genetic polymorphisms and defects affecting iron handling. PMID- 26274916 TI - Risk Factors for Death from Visceral Leishmaniasis in an Urban Area of Brazil. AB - BACKGROUND: Over the last three decades, the epidemiological profile of visceral leishmaniasis (VL) has changed with epidemics occurring in large urban centers of Brazil, an increase in HIV/AIDS co-infection, and a significant increase in mortality. The objective of this study was to identify the risk factors associated with death among adult patients with VL from an urban endemic area of Brazil. METHODOLOGY: A prospective cohort study included 134 adult patients with VL admitted to the University Hospital of the Federal University of Mato Grosso do Sul between August 2011 and August 2013. PRINCIPAL FINDINGS: Patients ranged from 18 to 93 years old, with a mean age of 43.6 (+/-15.7%). Of these patients, 36.6% were co-infected with HIV/AIDS, and the mortality rate was 21.6%. In a multivariate analysis, the risk factors associated with death were secondary bacterial infection (42.86, 5.05-363.85), relapse (12.17, 2.06-71.99), edema (7.74, 1.33-45.05) and HIV/AIDS co-infection (7.33, 1.22-43.98). CONCLUSIONS/SIGNIFICANCE: VL has a high mortality rate in adults from endemic urban areas, especially when coinciding with high rates of HIV/AIDS co-infection. PMID- 26274918 TI - Recovery of Drug Delivery Nanoparticles from Human Plasma Using an Electrokinetic Platform Technology. AB - The effect of complex biological fluids on the surface and structure of nanoparticles is a rapidly expanding field of study. One of the challenges holding back this research is the difficulty of recovering therapeutic nanoparticles from biological samples due to their small size, low density, and stealth surface coatings. Here, the first demonstration of the recovery and analysis of drug delivery nanoparticles from undiluted human plasma samples through the use of a new electrokinetic platform technology is presented. The particles are recovered from plasma through a dielectrophoresis separation force that is created by innate differences in the dielectric properties between the unaltered nanoparticles and the surrounding plasma. It is shown that this can be applied to a wide range of drug delivery nanoparticles of different morphologies and materials, including low-density nanoliposomes. These recovered particles can then be analyzed using different methods including scanning electron microscopy to monitor surface and structural changes that result from plasma exposure. This new recovery technique can be broadly applied to the recovery of nanoparticles from high conductance fluids in a wide range of applications. PMID- 26274919 TI - Strong Selective Sweeps on the X Chromosome in the Human-Chimpanzee Ancestor Explain Its Low Divergence. AB - The human and chimpanzee X chromosomes are less divergent than expected based on autosomal divergence. We study incomplete lineage sorting patterns between humans, chimpanzees and gorillas to show that this low divergence can be entirely explained by megabase-sized regions comprising one-third of the X chromosome, where polymorphism in the human-chimpanzee ancestral species was severely reduced. We show that background selection can explain at most 10% of this reduction of diversity in the ancestor. Instead, we show that several strong selective sweeps in the ancestral species can explain it. We also report evidence of population specific sweeps in extant humans that overlap the regions of low diversity in the ancestral species. These regions further correspond to chromosomal sections shown to be devoid of Neanderthal introgression into modern humans. This suggests that the same X-linked regions that undergo selective sweeps are among the first to form reproductive barriers between diverging species. We hypothesize that meiotic drive is the underlying mechanism causing these two observations. PMID- 26274921 TI - Correction: Estimated Dietary Intake of Radionuclides and Health Risks for the Citizens of Fukushima City, Tokyo, and Osaka after the 2011 Nuclear Accident. PMID- 26274920 TI - Reliability of Serum Metabolites over a Two-Year Period: A Targeted Metabolomic Approach in Fasting and Non-Fasting Samples from EPIC. AB - OBJECTIVE: Although metabolic profiles have been associated with chronic disease risk, lack of temporal stability of metabolite levels could limit their use in epidemiological investigations. The present study aims to evaluate the reliability over a two-year period of 158 metabolites and compare reliability over time in fasting and non-fasting serum samples. METHODS: Metabolites were measured with the AbsolueIDQp180 kit (Biocrates, Innsbruck, Austria) by mass spectrometry and included acylcarnitines, amino acids, biogenic amines, hexoses, phosphatidylcholines and sphingomyelins. Measurements were performed on repeat serum samples collected two years apart in 27 fasting men from Turin, Italy, and 39 non-fasting women from Utrecht, The Netherlands, all participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Reproducibility was assessed by estimating intraclass correlation coefficients (ICCs) in multivariable mixed models. RESULTS: In fasting samples, a median ICC of 0.70 was observed. ICC values were <0.50 for 48% of amino acids, 27% of acylcarnitines, 18% of lysophosphatidylcholines and 4% of phosphatidylcholines. In non-fasting samples, the median ICC was 0.54. ICC values were <0.50 for 71% of acylcarnitines, 48% of amino acids, 44% of biogenic amines, 36% of sphingomyelins, 34% of phosphatidylcholines and 33% of lysophosphatidylcholines. Overall, reproducibility was lower in non-fasting as compared to fasting samples, with a statistically significant difference for 19-36% of acylcarnitines, phosphatidylcholines and sphingomyelins. CONCLUSION: A single measurement per individual may be sufficient for the study of 73% and 52% of the metabolites showing ICCs >0.50 in fasting and non-fasting samples, respectively. ICCs were higher in fasting samples that are preferable to non-fasting. PMID- 26274922 TI - Real-Time PCR Assays for the Quantification of HCV RNA: Concordance, Discrepancies and Implications for Response Guided Therapy. AB - BACKGROUND AND AIMS: Monitoring of chronic Hepatitis C (CHC) treatment relies on HCV RNA quantification by means of real-time PCR methods. Assay specific analytical sensitivities may impact therapy management. METHODS: Comparative analysis between three commercial assays (Roche COBAS AmpliPrep/COBAS TaqMan Version 1 (CAP/CTM Ver. 1), Version 2 (CAP/CTM Ver. 2) and the Abbott RealTime HCV (ART) assay) was performed on 247 available samples taken at key decision time points during antiviral therapy of 105 genotype 1 patients (triple therapy: n = 70; dual therapy: n = 35). RESULTS: Overall concordance of HCV RNA measurements was high between the two Roche systems (89%; n = 220/247) but lower between the Roche assays and the ART (CAP/CTM Ver. 1 vs ART: 77.3%; n = 191/247 and CAP/CTM v.2 vs ART: 80.1%; n = 198/247). Most discrepancies were noted in week 4/8 samples with residual viremia (=50 mg/kg/d, 10 cases). The expression and distribution of VEGFA and VEGF receptor 2 (VEGFR2) in the GFB, the phosphorylation of VEGFR2 (p-VEGFR2) and nephrin (p-nephrin), and the expression of synaptopodin and nephrin in the glomeruli were detected by immune electron microscopy and/or immunofluorescence, and their relationships to proteinuria in AS patients were analyzed. The accumulation of VEGFA in the GBM was increased in AS patients. The expression of VEGFA and the levels of p-VEGFR2 and p-nephrin in glomeruli were increased and were positively correlated with the degree of proteinuria in AS patients. The expression of synaptopodin and nephrin were decreased and were negatively correlated with the degree of proteinuria in AS patients. The over expressed VEGFA in the glomeruli and its accumulation in the GBM may activate the VEGFA VEGFR2 and nephrin signaling pathways and lead to podocyte injury and occurrence of proteinuria in AS. PMID- 26274925 TI - The Impact of Opportunistic Infections on Clinical Outcome and Healthcare Resource Uses for Adult T Cell Leukaemia. AB - We examined the impact of opportunistic infections on in-hospital mortality, hospital length of stay (LOS), and the total cost (TC) among adult T-cell leukaemia (ATL) patients. In this retrospective cohort study, we identified 3712 patients with ATL using national hospital administrative data. Analysed opportunistic infections included Aspergillus spp., Candida spp., cytomegalovirus (CMV), herpes simplex virus (HSV), pneumocystis pneumonia (PCP), tuberculosis, varicella zoster virus (VZV), Cryptococcus spp., nontuberculous mycobacteria, and Strongyloides spp. Multilevel logistic regression analysis for in-hospital mortality and a multilevel linear regression analysis for LOS and TC were employed to determine the impact of opportunistic infections on clinical outcomes and healthcare resources. We found ATL patients infected with CMV had significantly higher in-hospital mortality (adjusted odds ratio (AOR) 2.29 [1.50 3.49] p < 0.001), longer LOS (coefficient (B): 0.13 [0.06-0.20] p < 0.001) and higher TC (B: 0.25 [0.17-0.32] p < 0.001) than those without CMV. Those with CAN and PCP were associated with a lower in-hospital mortality rate (AOR 0.72 [0.53 0.98] p = 0.035 and 0.54[0.41-0.73] p < 0.001, respectively) than their infections. VZV was associated with longer LOS (B: 0.13 [0.06-0.19] p < 0.001), while aspergillosis, HSV, or VZV infections were associated with higher TC (B: 0.16 [0.07-0.24] p < 0.001, 0.12 [0.02-0.23] p = 0.025, and 0.17 [0.10-0.24] p < 0.001, respectively). Our findings reveal that CMV infection is a major determinant of poor prognosis in patients affected by ATL. PMID- 26274926 TI - Sterility and Sexual Competitiveness of Tapachula-7 Anastrepha ludens Males Irradiated at Different Doses. AB - A genetic sexing strain of Anastrepha ludens (Loew), Tapachula-7, was developed by the Mexican Program Against Fruit Flies to produce and release only males in programs where the sterile insect technique (SIT) is applied. Currently, breeding are found at a massive scale, and it is necessary to determine the optimum irradiation dose that releases sterile males with minimum damage to their sexual competitiveness. Under laboratory and field conditions, we evaluated the effects of gamma irradiation at doses of 0, 20, 40, 60 and 80 Gy on the sexual competitiveness of males, the induction of sterility in wild females and offspring survivorship. The results of the study indicate that irradiation doses have a significant effect on the sexual behavior of males. A reduction of mating capacity was inversely proportional to the irradiation dose of males. It is estimated that a dose of 60 Gy can induce more than 99% sterility in wild females. In all treatments, the degree of offspring fertility was correlated with the irradiation dose of the parents. In conclusion, the results of the study indicate that a dose of 60 Gy can be applied in sterile insect technique release programs. The application of this dose in the new genetic sexing strain of A. ludens is discussed. PMID- 26274927 TI - Context Sensitive Modeling of Cancer Drug Sensitivity. AB - Recent screening of drug sensitivity in large panels of cancer cell lines provides a valuable resource towards developing algorithms that predict drug response. Since more samples provide increased statistical power, most approaches to prediction of drug sensitivity pool multiple cancer types together without distinction. However, pan-cancer results can be misleading due to the confounding effects of tissues or cancer subtypes. On the other hand, independent analysis for each cancer-type is hampered by small sample size. To balance this trade-off, we present CHER (Contextual Heterogeneity Enabled Regression), an algorithm that builds predictive models for drug sensitivity by selecting predictive genomic features and deciding which ones should-and should not-be shared across different cancers, tissues and drugs. CHER provides significantly more accurate models of drug sensitivity than comparable elastic-net-based models. Moreover, CHER provides better insight into the underlying biological processes by finding a sparse set of shared and type-specific genomic features. PMID- 26274928 TI - Soluble Forms and Ligands of the Receptor for Advanced Glycation End-Products in Patients with Acute Respiratory Distress Syndrome: An Observational Prospective Study. AB - BACKGROUND: The main soluble form of the receptor for advanced glycation end products (sRAGE) is elevated during acute respiratory distress syndrome (ARDS). However other RAGE isoforms and multiple ligands have been poorly reported in the clinical setting, and their respective contribution to RAGE activation during ARDS remains unclear. Our goal was therefore to describe main RAGE isoforms and ligands levels during ARDS. METHODS: 30 ARDS patients and 30 mechanically ventilated controls were prospectively included in this monocenter observational study. Arterial, superior vena cava and alveolar fluid levels of sRAGE, endogenous-secretory RAGE (esRAGE), high mobility group box-1 protein (HMGB1), S100A12 and advanced glycation end-products (AGEs) were measured in duplicate ELISA on day 0, day 3 and day 6. In patients with ARDS, baseline lung morphology was assessed with computed tomography. RESULTS: ARDS patients had higher arterial, central venous and alveolar levels of sRAGE, HMGB1 and S100A12, but lower levels of esRAGE and AGEs, than controls. Baseline arterial sRAGE, HMGB1 and S100A12 were correlated with nonfocal ARDS (AUC 0.79, 0.65 and 0.63, respectively). Baseline arterial sRAGE, esRAGE, S100A12 and AGEs were associated with severity as assessed by PaO2/FiO2. CONCLUSIONS: This is the first kinetics study of levels of RAGE main isoforms and ligands during ARDS. Elevated sRAGE, HMGB1 and S100A12, with decreased esRAGE and AGEs, were found to distinguish patients with ARDS from those without. Our findings should prompt future studies aimed at elucidating RAGE/HMGB1/S100A12 axis involvement in ARDS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01270295. PMID- 26274930 TI - Nonpharmacological treatments for patients with Parkinson's disease. AB - Since 2013, a number of studies have enhanced the literature and have guided clinicians on viable treatment interventions outside of pharmacotherapy and surgery. Thirty-three randomized controlled trials and one large observational study on exercise and physiotherapy were published in this period. Four randomized controlled trials focused on dance interventions, eight on treatment of cognition and behavior, two on occupational therapy, and two on speech and language therapy (the latter two specifically addressed dysphagia). Three randomized controlled trials focused on multidisciplinary care models, one study on telemedicine, and four studies on alternative interventions, including music therapy and mindfulness. These studies attest to the marked interest in these therapeutic approaches and the increasing evidence base that places nonpharmacological treatments firmly within the integrated repertoire of treatment options in Parkinson's disease. PMID- 26274929 TI - Immature B Cell Egress from Bone Marrow Is SOCS3 Independent. AB - Suppressor of cytokine signaling (SOCS)-3 has been suggested to regulate CXCR4 signaling in a variety of human cell lines. In mice, conditional SOCS3 inactivation in hematopoietic cells including B-lineage lymphocytes has been reported to exacerbate CXCR4-signaling and focal adhesion kinase phosphorylation, which resulted in altered immature B cell distribution in bone marrow (BM) due to sustained alpha4beta1 integrin-mediated adhesion to the extracellular matrix. However, a recent study examining conditional SOCS3 deletion specifically in B lineage cells failed to detect significant roles in B-lineage cell retention in BM. In this study we carefully examined the role played by SOCS3 in CXCR4 signaling in developing B cell subsets. We show that in mice conditionally deficient in SOCS3 exclusively in B cells (Socs3fl/fl Mb1cre/+) there was no detectable difference in B cell development in BM and in periphery. We show that SOCS3 deficient and sufficient immature B cell subsets are similarly distributed between BM parenchyma and sinusoids, and are equally competent at exiting BM into peripheral blood. Furthermore, we found no significant differences in CXCR4 desensitization upon ligand exposure in developing B lymphocyte subsets. Consequently, SOCS3-deficient and sufficient B-lineage cell migration towards CXCL12 in vitro was undistinguishable, and B-lineage cell amoeboid motility within BM parenchyma was also unaffected by SOCS3-deficiency. Thus we conclude that SOCS3 has no detectable influence on biological processes known to be controlled by CXCR4 signaling. PMID- 26274931 TI - Additive solutions differentially affect metabolic and functional parameters of platelet concentrates. AB - BACKGROUND: Pathogen inactivation (PI) of platelet concentrates with extension of shelf life to 7 days requires the use of platelet additive solutions (PAS). We examined the quality of platelets resuspended in three different PAS stored for up to 7 days. MATERIALS AND METHODS: Twelve triple adult dose platelet concentrates (PC) were collected using the TrimaAccel(r) collection system. Each highly concentrated product was divided into three equal parts, and the additive solutions (Composol(r) or SSP+(r) or IntersolTM) were added to a final concentration of 56% PAS and 44% plasma. Samples were drawn on days 1, 5 and 7 to measure pH, glucose, lactate dehydrogenase (LDH), lactate, mean platelet volume (MPV) and the aggregation response to collagen and the thrombin receptor agonist peptide-6. Further, p-selectin expression on platelets was assessed. RESULTS: No statistically significant changes were observed for pH and MPV during 7 days of storage in all PAS containing PCs, whereas glucose decreased and LDH and lactate increased over time (P < 0.05). These changes were particularly evident in Intersol PCs on days 5 and 7 compared with Composol(r) PCs or SSP+(r) PCs (P < 0.05). Platelets from Intersol PCs exhibited the highest baseline activation of p selectin and showed reduced collagen- and TRAP-6-induced aggregation. CONCLUSION: Resuspension of platelets in Intersol for 7 days results in increased platelet activation and platelet metabolism compared with SSP+(r) or Composol(r). Further clinical studies are needed to evaluate whether the observed differences in PAS PCs affect the recovery rate or the life span of transfused platelets. PMID- 26274932 TI - Effect of Erbium on the Photocatalytic Activity of TiO2 /Ag Nanocomposites under Visible Light Irradiation. AB - Erbium co-doped TiO2 /Ag catalysts are synthesized by using a simple, one-step solvothermal method and characterized by X-ray diffraction, field-emission scanning electron microscopy, transmission electron microscopy, Raman analysis, X ray photoelectron spectroscopy, and diffuse reflectance spectroscopy. The catalysts exhibit anatase crystal structures with increased visible light absorption compared with pure TiO2 . Enhanced photocatalytic activity is observed with Er co-doped TiO2 /Ag nanocomposites for Rhodamine B degradation under visible light irradiation. The photocatalytic activity of 1 % Er co-doped TiO2 /Ag is much higher than that of TiO2 /Ag, TiO2 /Er, pure TiO2 , and commercial Degussa P25. The kinetics of the degradation process are studied and the pseudo first-order rate constant (k) and half-life time (t1/2 ) of the reaction are calculated. The enhanced activity might be accredited to the efficient separation of electron-hole pairs by silver and higher visible light absorption of TiO2 induced by Er. PMID- 26274933 TI - A method to assess relative preference for training and environmental enrichment in captive wolves (Canis lupus and Canis lupus arctos). AB - It is currently debated as to whether or not positive reinforcement training is enriching to captive animals. Although both husbandry training and environmental enrichment (EE) have been found to benefit animal welfare in captivity, to date, no systematic investigation has compared an animal's preference for performing a trained behavior to engaging freely with a stimuli provided as EE. In the current paper, we used four captive wolves to (1) test the efficacy of a paired-stimulus preference assessment to determine preference for engaging in a trained behavior as a choice; and to (2) use a paired-stimulus preference assessment to determine whether or not individuals prefer to engage in a previously trained behavior versus a previously encountered EE stimuli. Of the four subjects tested, visual inspection of the graphs revealed that two of the subjects preferred trained behavior stimuli and two of the subjects preferred EE stimuli; only one of the wolves had a statically higher preference for an EE stimulus over a trained behavior. We believe that letting the animals choose between these two events is the first step in answering the question of whether or not is training enriching, however more research needs to be done and suggestions for future research is discussed. PMID- 26274934 TI - A Combined Experimental and Theoretical Study on the Stereodynamics of Monoaza[5]helicenes: Solvent-Induced Increase of the Enantiomerization Barrier in 1-Aza-[5]helicene. AB - Helicenes and heterohelicenes are attractive compounds with great potential in materials sciences to be used in optoelectronics as ligand backbones in enantioselective catalysis and as chiral sensors. The properties of these materials are related to the stereodynamics of these helical chiral compounds. However, little is known about features controlling stereodynamics in helicenes; in particular, for heterohelicenes the position of the heteroatom could be relevant in this respect. Herein the complete stereodynamic characterization of monoaza[5]helicenes is shown by enantioselective dynamic HPLC and DFT calculations. At variance with previous theoretical calculations, 1 aza[5]helicene shows a surprisingly high enantiomerization barrier, which is triggered by specific solvent interactions. PMID- 26274935 TI - How to Respond to a Paranoid Thought: A Comparison of Patients With Clinically Relevant Delusions and Healthy Controls in Chile. AB - Although paranoid thoughts occur frequently in the population, most people do not develop clinically relevant delusions. The main purpose of the study was to explore whether participants without a mental disorder will respond in a more functional way to paranoid thoughts and be more flexible in their cognitive processes than patients with clinically relevant delusions. The Responses to Paranoid Thoughts Scale was translated into Spanish and was completed by patients (n = 36) and healthy controls (n = 39) in Chile (South America). The Beck Cognitive Insight Scale was used to assess cognitive insight. The patients responded in a more depressive, physical, and concealing way to paranoid thoughts than the healthy controls. Moreover, they showed significantly less cognitive insight and self-reflectiveness. Higher cognitive insight and self-reflectiveness were associated with more normalizing and communicative responses to paranoid thoughts. PMID- 26274936 TI - Television viewing and hostile personality trait increase the risk of injuries. AB - Individuals with high levels of hostility may be more susceptible to the influence of television on violence and risk taking behaviors. This study aimed to examine whether hostile personality trait modifies the association between TV viewing and injuries. It is a prospective study of 4,196 black and white adults aged 23 to 35 in 1990/1. Cross-lagged panel models were analyzed at three 5-year time periods to test whether TV viewing predicted injuries. Covariates were gender, race, and education. Individuals who watched more TV (0 hours, 1-3 hours, 4-6 hours, and >=7 hours) were more likely to have a hospitalization for an injury in the following 5 years across each of the three follow-up periods [OR = 1.5 (95%CI = 1.2, 1.9), 1.5 (1.1, 1.9), and 1.9 (1.3, 2.6)]. The cross-lagged effects of TV viewing to injury were significant in the high hostility group [OR = 1.4 (95%CI = 1.1, 1.8), 1.3 (1.0, 1.8), and 2.0 (1.3, 2.9)] but not in the low hostility group [OR = 1.3 (95%CI = 0.6, 2.2), 1.1 (0.6, 2.1), and 1.4 (0.7, 2.8)]. Additionally, a statistically significant difference between the two models (P < 0.001) suggested that hostility moderated the relationship between TV watching and injury. These findings suggest that individuals who watch more TV and have a hostile personality trait may be at a greater risk for injury. PMID- 26274937 TI - The effectiveness of three home products in cleaning and disinfection of Staphylococcus aureus and Escherichia coli on home environmental surfaces. AB - AIMS: The objectives of this study were to investigate three products for: (i) cleaning effectiveness on two common household surfaces, and (ii) disinfection effectiveness against two common bacteria. Products included conventional ('bleach'), environmentally preferable (EP), do-it-yourself (DIY: distilled white vinegar, club soda, tea tree oil), 24-h old DIY, and individual DIY components in dilution. METHODS AND RESULTS: For cleaning ceramic, no product was effective (>=85% removal of Hucker's soil), however, DIY performed better than EP and bleach. On stainless, only DIY failed to meet the standard. For disinfection, bleach and EP achieved >=5.00 log10 reductions under all conditions. DIY and components were more active against Escherichia coli than Staphylococcus aureus but only fresh DIY and 50% vinegar achieved >=5.00 log10 reductions. CONCLUSIONS: EP is an effective alternative to bleach. DIY may be an adequate alternative for cleaning ceramic and for household use, where complete elimination of micro organisms is unnecessary; however, it must be freshly prepared each day. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of performance of purportedly safer alternatives for both cleaning and disinfection for use in home health care. The EP product and DIY are potential alternatives for some household uses. PMID- 26274938 TI - Differential short-term memorisation for vocal and instrumental rhythms. AB - This study explores differential processing of vocal and instrumental rhythms in short-term memory with three decision (same/different judgments) and one reproduction experiment. In the first experiment, memory performance declined for delayed versus immediate recall, with accuracy for the two rhythms being affected differently: Musicians performed better than non-musicians on clapstick but not on vocal rhythms, and musicians were better on vocal rhythms in the same than in the different condition. Results for the second experiment showed that concurrent sub-vocal articulation and finger-tapping differentially affected the two rhythms and same/different decisions, but produced no evidence for articulatory loop involvement in delayed decision tasks. In a third experiment, which tested rhythm reproduction, concurrent sub-vocal articulation decreased memory performance, with a stronger deleterious effect on the reproduction of vocal than of clapstick rhythms. This suggests that the articulatory loop may only be involved in delayed reproduction not in decision tasks. The fourth experiment tested whether differences between filled and empty rhythms (continuous vs. discontinuous sounds) can explain the different memorisation of vocal and clapstick rhythms. Though significant differences were found for empty and filled instrumental rhythms, the differences between vocal and clapstick can only be explained by considering additional voice specific features. PMID- 26274939 TI - Atypical Chronic Myeloid Leukemia in Two Pediatric Patients. AB - Atypical chronic myeloid leukemia, BCR-ABL1-negative, (aCML) is a rare myeloid neoplasm. Recent adult data suggest the leukemic cells in a subset of patients are dependent on JAK/STAT signaling and harbor CSF3R-activating mutations. We hypothesized that, similar to adult patients, the presence of CSF3R-activating mutations would be clinically relevant in pediatric myeloid neoplasms as patients would be sensitive to the JAK inhibitor, ruxolitinib. We report two cases of morphologically similar pediatric aCML, BCR-ABL1-negative based on WHO 2008 criteria. One patient had CSF3R-activating mutation (T618I) and demonstrated a robust response to ruxolitinib, which was used to bridge to a successful stem cell transplant. The other patient did not have a CSF3R-activating mutation and succumbed to refractory disease <6 months from diagnosis. This report documents CSF3R-T618I in pediatric aCML and demonstrates the efficacy of ruxolitinib in a pediatric malignancy. As the third documented case successfully treating aCML with ruxolitinib, this case highlights the importance of prompt CSF3R sequencing analysis for myeloproliferative and myelodysplastic/myeloproliferative neoplasms. PMID- 26274940 TI - Simultaneous exposure to chronic hypoxia and dissolved polycyclic aromatic hydrocarbons results in reduced egg production and larval survival in the sheepshead minnow (Cyprinodon variegatus). AB - Estuarine fish in the northern Gulf of Mexico are exposed annually to hypoxic conditions. In addition to hypoxia, fish located throughout the northern Gulf of Mexico were potentially exposed to oil released during the Deepwater Horizon incident. Therefore, the interaction between oil exposure and hypoxia is worth investigating. To examine this interaction, the authors exposed adult and larval sheepshead minnow (Cyprinodon variegatus) to crude or dispersed oil under both normoxic and hypoxic conditions. The authors examined total egg production, egg hatching success, and larval survival post hatch. The authors' results indicate that co-exposure to crude or dispersed oil and hypoxia resulted in a significant decrease in egg production, as well as a significant decrease in both egg hatch success and larval survival post hatch. The significant impact on reproductive success following crude or dispersed oil and hypoxia exposure indicates the importance of including environmental parameters such as hypoxia when evaluating the impact of an oil spill. PMID- 26274941 TI - Understanding complex chiral plasmonics. AB - Chiral nanoplasmonics exhibits great potential for novel nanooptical devices due to the generation of a strong chiroptical response within nanoscale metallic structures. Recently, a number of different approaches have been utilized to create chiral nanoplasmonic structures. However, particularly for tailoring nanooptical chiral sensing devices, the understanding of the resulting chiroptical response when coupling chiral and achiral structures together is crucial and has not been completely understood to date. Here, we present a thorough and step-by-step experimental study to understand the intriguing chiral achiral coupling scheme. We set up a hybrid plasmonic system, which bears resemblance to the 'host-guest' system in supramolecular chemistry to analyze and explain the complex chiral response both at the chiral and achiral plasmonic resonances. We also provide an elegant and simple analytical model, which can describe, predict, and comprehend the chiroptical spectra in detail. Our study will shed light on designing well-controlled chiral-achiral coupling platforms for reliable chiral sensing. PMID- 26274942 TI - Direct Exchange of Oxygen and Selenium Atoms in the 1,2,5-Oxadiazoles and 1,2,5 Selenadiazoles by Action of Sulfur Monochloride. AB - A short synthetic approach to fused 1,2,5-thiadiazoles from the corresponding 1,2,5-oxadiazoles and 1,2,5-selenadiazoles has been developed. Mono- and bis(1,2,5-thiadiazoles) were selectively obtained in high yields. The pathways for these novel reactions were discussed. PMID- 26274943 TI - Prazosin-Conjugated Matrices Based on Biodegradable Polymers and alpha-Amino Acids--Synthesis, Characterization, and in Vitro Release Study. AB - Novel and promising macromolecular conjugates of the alpha1-adrenergic blocker prazosin were directly synthesized by covalent incorporation of the drug to matrices composed of biodegradable polymers and alpha-amino acids for the development of a polymeric implantable drug delivery carrier. The cyto- and genotoxicity of the synthesized matrices were evaluated using a bacterial luminescence test, protozoan assay, and Salmonella typhimurium TA1535. A new urethane bond was formed between the hydroxyl end-groups of the synthesized polymer matrices and an amine group of prazosin, using 1,1'-carbonyldiimidazole (CDI) as a coupling agent. The structure of the polymeric conjugates was characterized by various spectroscopy techniques. A study of hydrogen nuclear magnetic resonance ((1)H-NMR) and differential scanning calorimetry (DSC) thermodiagrams indicated that the presence of prazosin pendant groups in the macromolecule structures increased the polymer's rigidity alongside increasing glass transition temperature. It has been found that the kinetic release of prazosin from the obtained macromolecular conjugates, tested in vitro under different conditions, is strongly dependent on the physicochemical properties of polymeric matrices. Furthermore, the presence of a urethane bond in the macromolecular conjugates allowed for obtaining a relatively controlled release profile of the drug. The obtained results confirm that the pharmacokinetics of prazosin might be improved through the synthesis of polymeric conjugates containing biomedical polymers and alpha-amino acids in the macromolecule. PMID- 26274944 TI - Optical Properties of Titania Coatings Prepared by Inkjet Direct Patterning of a Reverse Micelles Sol-Gel Composition. AB - Thin layers of titanium dioxide were fabricated by direct inkjet patterning of a reverse micelles sol-gel composition onto soda-lime glass plates. Several series of variable thickness samples were produced by repeated overprinting and these were further calcined at different temperatures. The resulting layers were inspected by optical and scanning electronic microscopy and their optical properties were investigated by spectroscopic ellipsometry in the range of 200 1000 nm. Thus the influence of the calcination temperature on material as well as optical properties of the patterned micellar titania was studied. The additive nature of the deposition process was demonstrated by a linear dependence of total thickness on the number of printed layers without being significantly affected by the calcination temperature. The micellar imprints structure of the titania layer resulted into significant deviation of measured optical constants from the values reported for bulk titania. The introduction of a void layer into the ellipsometric model was found necessary for this particular type of titania and enabled correct ellipsometric determination of layer thickness, well matching the thickness values from mechanical profilometry. PMID- 26274945 TI - Four New Cyclohexylideneacetonitrile Derivatives from the Hypocotyl of Mangrove (Bruguiera gymnorrhiza). AB - Four new cyclohexylideneacetonitrile derivatives 1-4, named menisdaurins B-E, as well as three known cyclohexylideneacetonitrile derivatives--menisdaurin (5), coclauril (6), and menisdaurilide (7)--were isolated from the hypocotyl of a mangrove (Bruguiera gymnorrhiza). The structures of the isolates were elucidated on the basis of extensive spectroscopic analysis. Compounds 1-7 showed anti Hepatitis B virus (HBV) activities, with EC50 values ranging from 5.1 +/- 0.2 MUg/mL to 87.7 +/- 5.8 MUg/mL. PMID- 26274946 TI - A Qualitative Comparison of the Reactivities of 3,4,4,5-Tetrachloro-4H-1,2,6 thiadiazine and 4,5-Dichloro-1,2,3-dithiazolium Chloride. AB - The high yielding transformations of 3,4,4,5-tetrachloro-4H-1,2,6-thiadiazine into 3,5-dichloro-4H-1,2,6-thiadiazin-4-one (up to 85%) and 2-(3,5-dichloro-4H 1,2,6-thiadiazin-4-ylidene)malononitrile (up to 83%) have been investigated and compared to the analogous transformations of the closely-related 4,5-dichloro 1,2,3-dithiazolium chloride (Appel's salt) into 4-chloro-5H-1,2,3-dithiazol-5-one and 2-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)malononitrile. Furthermore, cyclocondensation of 3,4,4,5-tetrachloro-4H-1,2,6-thiadiazine with 2-aminophenol and 1,2-benzenediamines gave fused 4H-1,2,6-thiadiazines in 68%-85% yields. PMID- 26274947 TI - 3-H-[1,2]Dithiole as a New Anti-Trypanosoma cruzi Chemotype: Biological and Mechanism of Action Studies. AB - The current pharmacological Chagas disease treatments, using Nifurtimox or Benznidazole, show limited therapeutic results and are associated with potential side effects, like mutagenicity. Using random screening we have identified new chemotypes that were able to inhibit relevant targets of the Trypanosoma cruzi. We found 3H-[1,2]dithioles with the ability to inhibit Trypanosoma cruzi triosephosphate isomerase (TcTIM). Herein, we studied the structural modifications of this chemotype to analyze the influence of volume, lipophilicity and electronic properties in the anti-T. cruzi activity. Their selectivity to parasites vs. mammalian cells was also examined. To get insights into a possible mechanism of action, the inhibition of the enzymatic activity of TcTIM and cruzipain, using the isolated enzymes, and the inhibition of membrane sterol biosynthesis and excreted metabolites, using the whole parasite, were achieved. We found that this structural framework is interesting for the generation of innovative drugs for the treatment of Chagas disease. PMID- 26274948 TI - New Bergamotane Sesquiterpenoids from the Plant Endophytic Fungus Paraconiothyrium brasiliense. AB - Brasilamides K-N (1-4), four new bergamotane sesquiterpenoids; with 4-oxatricyclo (3.3.1.0 (2,7))nonane (1)and 9-oxatricyclo(4.3.0.0 (4,7))nonane (2-4) skeletons; were isolated from the scale-up fermentation cultures of the plant endophytic fungus Paraconiothynium brasiliense Verkley. The previously identified sesquiterpenoids brasilamides A and C (5 and 6) were also reisolated in the current work. The structures of 1-4 were elucidated primarily by interpretation of NMR spectroscopic data. The absolute configurations of 1-3 were deduced by analogy to the co-isolated metabolites 5 and 6; whereas that of C-12 in 4 was assigned using the modified Mosher method. The cytotoxicity of all compounds against a panel of eight human tumor cell lines were assayed. PMID- 26274949 TI - Regulation of the scp Genes in the Cyanobacterium Synechocystis sp. PCC 6803- What is New? AB - In the cyanobacterium Synechocystis sp. PCC 6803 there are five genes encoding small CAB-like (SCP) proteins, which have been shown to be up-regulated under stress. Analyses of the promoter sequences of the scp genes revealed the existence of an NtcA binding motif in two scp genes, scpB and scpE. Binding of NtcA, the key transcriptional regulator during nitrogen stress, to the promoter regions was shown by electrophoretic mobility shift assay. The metabolite 2 oxoglutarate did not increase the affinity of NtcA for binding to the promoters of scpB and scpE. A second motif, the HIP1 palindrome 5' GGCGATCGCC 3', was detected in the upstream regions of scpB and scpC. The transcription factor encoded by sll1130 has been suggested to recognize this motif to regulate heat responsive genes. Our data suggest that HIP1 is not a regulatory element within the scp genes. Further, the presence of the high light regulatory (HLR1) motif was confirmed in scpB-E, in accordance to their induced transcriptions in cells exposed to high light. The HLR1 motif was newly discovered in eight additional genes. PMID- 26274950 TI - Quantitative Structure-Activity Relationships Study on the Rate Constants of Polychlorinated Dibenzo-p-Dioxins with OH Radical. AB - The OH-initiated reaction rate constants (kOH) are of great importance to measure atmospheric behaviors of polychlorinated dibenzo-p-dioxins (PCDDs) in the environment. The rate constants of 75 PCDDs with the OH radical at 298.15 K have been calculated using high level molecular orbital theory, and the rate constants (kalpha, kbeta, kgamma and kOH) were further analyzed by the quantitative structure-activity relationships (QSAR) study. According to the QSAR models, the relations between rate constants and the numbers and positions of Cl atoms, the energy of the highest occupied molecular orbital (EHOMO), the energy of the lowest unoccupied molecular orbital (ELUMO), the difference DeltaEHOMO-LUMO between EHOMO and ELUMO, and the dipole of oxidizing agents (D) were discussed. It was found that EHOMO is the main factor in the kOH. The number of Cl atoms is more effective than the number of relative position of these Cl atoms in the kOH. The kOH decreases with the increase of the substitute number of Cl atoms. PMID- 26274951 TI - Osteoclast Differentiation Is Impaired in a Subgroup of SLE Patients and Correlates Inversely with Mycophenolate Mofetil Treatment. AB - Osteoporosis can arise in systemic lupus erythematosus (SLE) patients secondary to medication and/or chronic inflammation. To analyze if patients with SLE have phenotypically-impaired osteoclastogenesis, we differentiated ex vivo monocytes from 72 SLE patients and 15 healthy individuals into osteoclasts followed by TRAP staining and counting. We identified a subgroup of SLE patients (45%) with a significantly impaired osteoclast differentiation, relative to the other SLE patients or healthy individuals (OR 11.2; 95% CI 1.4-89.9). A review of medication indicated that patients with osteoclast counts equal to healthy donors were significantly more likely to be treated with mycophenolate mofetil (MMF) compared to patients with impaired osteoclastogenesis. We analyzed expression of RANKL and the MMF target genes IMPDH1 and IMPDH2 in osteoclasts by qPCR, but detected no difference. Since MMF might influence interferon-alpha (IFNalpha) and -gamma (IFNgamma) we measured serum IFNalpha and IFNgamma levels. Patients with very low osteoclast counts also had comparably higher IFNalpha serum levels than patients with normal osteoclast counts. We conclude that in vitro osteoclastogenesis is impaired in a subgroup of SLE patients. This correlates inversely with MMF treatment and high IFNalpha serum levels. Further observational study will be required to determine whether this translates into a clinically meaningful effect. PMID- 26274952 TI - From Genome to Structure and Back Again: A Family Portrait of the Transcarbamylases. AB - Enzymes in the transcarbamylase family catalyze the transfer of a carbamyl group from carbamyl phosphate (CP) to an amino group of a second substrate. The two best-characterized members, aspartate transcarbamylase (ATCase) and ornithine transcarbamylase (OTCase), are present in most organisms from bacteria to humans. Recently, structures of four new transcarbamylase members, N-acetyl-L-ornithine transcarbamylase (AOTCase), N-succinyl-L-ornithine transcarbamylase (SOTCase), ygeW encoded transcarbamylase (YTCase) and putrescine transcarbamylase (PTCase) have also been determined. Crystal structures of these enzymes have shown that they have a common overall fold with a trimer as their basic biological unit. The monomer structures share a common CP binding site in their N-terminal domain, but have different second substrate binding sites in their C-terminal domain. The discovery of three new transcarbamylases, l-2,3-diaminopropionate transcarbamylase (DPTCase), l-2,4-diaminobutyrate transcarbamylase (DBTCase) and ureidoglycine transcarbamylase (UGTCase), demonstrates that our knowledge and understanding of the spectrum of the transcarbamylase family is still incomplete. In this review, we summarize studies on the structures and function of transcarbamylases demonstrating how structural information helps to define biological function and how small structural differences govern enzyme specificity. Such information is important for correctly annotating transcarbamylase sequences in the genome databases and for identifying new members of the transcarbamylase family. PMID- 26274953 TI - Major Alterations of Phosphatidylcholine and Lysophosphotidylcholine Lipids in the Substantia Nigra Using an Early Stage Model of Parkinson's Disease. AB - Parkinson's disease (PD) is a progressive neurodegenerative disease affecting the nigrostriatal pathway, where patients do not manifest motor symptoms until >50% of neurons are lost. Thus, it is of great importance to determine early neuronal changes that may contribute to disease progression. Recent attention has focused on lipids and their role in pro- and anti-apoptotic processes. However, information regarding the lipid alterations in animal models of PD is lacking. In this study, we utilized high performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) and novel HPLC solvent methodology to profile phosphatidylcholines and sphingolipids within the substantia nigra. The ipsilateral substantia nigra pars compacta was collected from rats 21 days after an infusion of 6-hydroxydopamine (6-OHDA), or vehicle into the anterior dorsal striatum. We identified 115 lipid species from their mass/charge ratio using the LMAPS Lipid MS Predict Database. Of these, 19 lipid species (from phosphatidylcholine and lysophosphotidylcholine lipid classes) were significantly altered by 6-OHDA, with most being down-regulated. The two lipid species that were up-regulated were LPC (16:0) and LPC (18:1), which are important for neuroinflammatory signalling. These findings provide a first step in the characterization of lipid changes in early stages of PD-like pathology and could provide novel targets for early interventions in PD. PMID- 26274954 TI - Detecting Antigen-Specific T Cell Responses: From Bulk Populations to Single Cells. AB - A new generation of sensitive T cell-based assays facilitates the direct quantitation and characterization of antigen-specific T cell responses. Single cell analyses have focused on measuring the quality and breadth of a response. Accumulating data from these studies demonstrate that there is considerable, previously-unrecognized, heterogeneity. Standard assays, such as the ICS, are often insufficient for characterization of rare subsets of cells. Enhanced flow cytometry with imaging capabilities enables the determination of cell morphology, as well as the spatial localization of the protein molecules within a single cell. Advances in both microfluidics and digital PCR have improved the efficiency of single-cell sorting and allowed multiplexed gene detection at the single-cell level. Delving further into the transcriptome of single-cells using RNA-seq is likely to reveal the fine-specificity of cellular events such as alternative splicing (i.e., splice variants) and allele-specific expression, and will also define the roles of new genes. Finally, detailed analysis of clonally related antigen-specific T cells using single-cell TCR RNA-seq will provide information on pathways of differentiation of memory T cells. With these state of the art technologies the transcriptomics and genomics of Ag-specific T cells can be more definitively elucidated. PMID- 26274956 TI - Nutritional Characterization and Phenolic Profiling of Moringa oleifera Leaves Grown in Chad, Sahrawi Refugee Camps, and Haiti. AB - Moringa oleifera is a plant that grows in tropical and subtropical areas of the world. Its leaves are rich of nutrients and bioactive compounds. However, several differences are reported in the literature. In this article we performed a nutritional characterization and a phenolic profiling of M. oleifera leaves grown in Chad, Sahrawi refugee camps, and Haiti. In addition, we investigated the presence of salicylic and ferulic acids, two phenolic acids with pharmacological activity, whose presence in M. oleifera leaves has been scarcely investigated so far. Several differences were observed among the samples. Nevertheless, the leaves were rich in protein, minerals, and beta-carotene. Quercetin and kaempferol glycosides were the main phenolic compounds identified in the methanolic extracts. Finally, salicylic and ferulic acids were found in a concentration range of 0.14-0.33 and 6.61-9.69 mg/100 g, respectively. In conclusion, we observed some differences in terms of nutrients and phenolic compounds in M. oleifera leaves grown in different countries. Nevertheless, these leaves are a good and economical source of nutrients for tropical and sub tropical countries. Furthermore, M. oleifera leaves are a source of flavonoids and phenolic acids, among which salicylic and ferulic acids, and therefore they could be used as nutraceutical and functional ingredients. PMID- 26274955 TI - Cardiovascular Disease Modeling Using Patient-Specific Induced Pluripotent Stem Cells. AB - The generation of induced pluripotent stem cells (iPSCs) has opened up a new scientific frontier in medicine. This technology has made it possible to obtain pluripotent stem cells from individuals with genetic disorders. Because iPSCs carry the identical genetic anomalies related to those disorders, iPSCs are an ideal platform for medical research. The pathophysiological cellular phenotypes of genetically heritable heart diseases such as arrhythmias and cardiomyopathies, have been modeled on cell culture dishes using disease-specific iPSC-derived cardiomyocytes. These model systems can potentially provide new insights into disease mechanisms and drug discoveries. This review focuses on recent progress in cardiovascular disease modeling using iPSCs, and discusses problems and future perspectives concerning their use. PMID- 26274959 TI - Towards the Development of a Low Cost Airborne Sensing System to Monitor Dust Particles after Blasting at Open-Pit Mine Sites. AB - Blasting is an integral part of large-scale open cut mining that often occurs in close proximity to population centers and often results in the emission of particulate material and gases potentially hazardous to health. Current air quality monitoring methods rely on limited numbers of fixed sampling locations to validate a complex fluid environment and collect sufficient data to confirm model effectiveness. This paper describes the development of a methodology to address the need of a more precise approach that is capable of characterizing blasting plumes in near-real time. The integration of the system required the modification and integration of an opto-electrical dust sensor, SHARP GP2Y10, into a small fixed-wing and multi-rotor copter, resulting in the collection of data streamed during flight. The paper also describes the calibration of the optical sensor with an industry grade dust-monitoring device, Dusttrak 8520, demonstrating a high correlation between them, with correlation coefficients (R(2)) greater than 0.9. The laboratory and field tests demonstrate the feasibility of coupling the sensor with the UAVs. However, further work must be done in the areas of sensor selection and calibration as well as flight planning. PMID- 26274957 TI - Protective Effects of Hong Shan Capsule against Lethal Total-Body Irradiation Induced Damage in Wistar Rats. AB - Hong Shan Capsule (HSC), a crude drug of 11 medicinal herbs, was used in clinical practice for the treatment of radiation injuries in China. In this study, we investigated its protection in rats against acute lethal total-body irradiation (TBI). Pre-administration of HSC reduced the radiation sickness characteristics, while increasing the 30-day survival of the irradiated rats. Administration of HSC also reduced the radiation sickness characteristics and increased the 30-day survival of mice after exposure to lethal TBI. Ultrastructural observation illustrated that the pretreatment of rats with HSC significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed the dramatic effect of HSC on alterations of gene expression caused by lethal TBI. Pretreatment with HSC prevented differential expression of 66% (1398 genes) of 2126 genes differentially expressed in response to TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 32 pathways, such as pathways in cancer and the mitogen-activated protein kinase (MAPK) signaling pathway. Our analysis indicated that the pretreatment of rats with HSC modulated these pathways induced by lethal TBI, such as multiple MAPK pathways, suggesting that pretreatment with HSC might provide protective effects on lethal TBI mainly or partially through the modulation of these pathways. Our data suggest that HSC has the potential to be used as an effective therapeutic or radio-protective agent to minimize irradiation damage. PMID- 26274958 TI - A Natural Triterpene Derivative from Euphorbia kansui Inhibits Cell Proliferation and Induces Apoptosis against Rat Intestinal Epithelioid Cell Line in Vitro. AB - Kansenone is a triterpene from the root of the traditional Chinese medicine, Euphorbia kansui. However, kansenone exerts serious toxicity, but the exact mechanism was not clear. In this work, the effects of kansenone on cell proliferation, cell cycle, cell damage, and cell apoptosis were investigated. The suppression of cell proliferation was assessed via the colorimetric MTT assay, and cell morphology was visualized via inverted microscopy after IEC-6 cells were incubated with different concentrations of kansenone. Reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA) content were detected for evaluating cell damage. RNase/propidium iodide (PI) labeling for evaluation of cell cycle distribution was performed by flow cytometry analysis. Annexin V fluorescein isothiocyanate (FITC)/PI and Hoechst 33342/Annexin V-FITC/PI staining assay for cell apoptosis detection were performed using confocal laser scanning microscopy and high content screening. Moreover, apoptosis induction was further confirmed by transmission electron microscope (TEM) and JC-1 mitochondrial membrane potential, western blot and RT-PCR analysis. The results demonstrated that kansenone exerted high cytotoxicity, induced cell arrest at G0/G1 phase, and caused mitochondria damage. In addition, kansenone could up-regulate the apoptotic proteins Bax, AIF, Apaf-1, cytochrome c, caspase-3, caspase-9, caspase 8, FasR, FasL, NF-kappaB, and TNFR1 mRNA expression levels, and down-regulate the anti-apoptotic Bcl-2 family proteins, revealing that kansenone induces apoptosis through both the death receptor and mitochondrial pathways. PMID- 26274960 TI - Spatial Quality Evaluation of Resampled Unmanned Aerial Vehicle-Imagery for Weed Mapping. AB - Unmanned aerial vehicles (UAVs) combined with different spectral range sensors are an emerging technology for providing early weed maps for optimizing herbicide applications. Considering that weeds, at very early phenological stages, are similar spectrally and in appearance, three major components are relevant: spatial resolution, type of sensor and classification algorithm. Resampling is a technique to create a new version of an image with a different width and/or height in pixels, and it has been used in satellite imagery with different spatial and temporal resolutions. In this paper, the efficiency of resampled images (RS-images) created from real UAV-images (UAV-images; the UAVs were equipped with two types of sensors, i.e., visible and visible plus near-infrared spectra) captured at different altitudes is examined to test the quality of the RS-image output. The performance of the object-based-image-analysis (OBIA) implemented for the early weed mapping using different weed thresholds was also evaluated. Our results showed that resampling accurately extracted the spectral values from high spatial resolution UAV-images at an altitude of 30 m and the RS image data at altitudes of 60 and 100 m, was able to provide accurate weed cover and herbicide application maps compared with UAV-images from real flights. PMID- 26274961 TI - High Frequency Sampling of TTL Pulses on a Raspberry Pi for Diffuse Correlation Spectroscopy Applications. AB - Diffuse Correlation Spectroscopy (DCS) is a well-established optical technique that has been used for non-invasive measurement of blood flow in tissues. Instrumentation for DCS includes a correlation device that computes the temporal intensity autocorrelation of a coherent laser source after it has undergone diffuse scattering through a turbid medium. Typically, the signal acquisition and its autocorrelation are performed by a correlation board. These boards have dedicated hardware to acquire and compute intensity autocorrelations of rapidly varying input signal and usually are quite expensive. Here we show that a Raspberry Pi minicomputer can acquire and store a rapidly varying time-signal with high fidelity. We show that this signal collected by a Raspberry Pi device can be processed numerically to yield intensity autocorrelations well suited for DCS applications. DCS measurements made using the Raspberry Pi device were compared to those acquired using a commercial hardware autocorrelation board to investigate the stability, performance, and accuracy of the data acquired in controlled experiments. This paper represents a first step toward lowering the instrumentation cost of a DCS system and may offer the potential to make DCS become more widely used in biomedical applications. PMID- 26274962 TI - An Auto-Tuning PI Control System for an Open-Circuit Low-Speed Wind Tunnel Designed for Greenhouse Technology. AB - Wind tunnels are a key experimental tool for the analysis of airflow parameters in many fields of application. Despite their great potential impact on agricultural research, few contributions have dealt with the development of automatic control systems for wind tunnels in the field of greenhouse technology. The objective of this paper is to present an automatic control system that provides precision and speed of measurement, as well as efficient data processing in low-speed wind tunnel experiments for greenhouse engineering applications. The system is based on an algorithm that identifies the system model and calculates the optimum PI controller. The validation of the system was performed on a cellulose evaporative cooling pad and on insect-proof screens to assess its response to perturbations. The control system provided an accuracy of <0.06 m.s( 1) for airflow speed and <0.50 Pa for pressure drop, thus permitting the reproducibility and standardization of the tests. The proposed control system also incorporates a fully-integrated software unit that manages the tests in terms of airflow speed and pressure drop set points. PMID- 26274963 TI - Shaft Diameter Measurement Using Structured Light Vision. AB - A method for measuring shaft diameters is presented using structured light vision measurement. After calibrating a model of the structured light measurement, a virtual plane is established perpendicular to the measured shaft axis and the image of the light stripe on the shaft is projected to the virtual plane. On the virtual plane, the center of the measured shaft is determined by fitting the projected image under the geometrical constraints of the light stripe, and the shaft diameter is measured by the determined center and the projected image. Experiments evaluated the measuring accuracy of the method and the effects of some factors on the measurement are analyzed. PMID- 26274964 TI - UWB Wind Turbine Blade Deflection Sensing for Wind Energy Cost Reduction. AB - A new application of utilizing ultra-wideband (UWB) technology to sense wind turbine blade deflections is introduced in this paper for wind energy cost reduction. The lower UWB band of 3.1-5.3 GHz is applied. On each blade, there will be one UWB blade deflection sensing system, which consists of two UWB antennas at the blade root and one UWB antenna at the blade tip. The detailed topology and challenges of this deflection sensing system are addressed. Due to the complexity of the problem, this paper will first realize the on-blade UWB radio link in the simplest case, where the tip antenna is situated outside (and on the surface of) a blade tip. To investigate this case, full-blade time-domain measurements are designed and conducted under different deflections. The detailed measurement setups and results are provided. If the root and tip antenna locations are properly selected, the first pulse is always of sufficient quality for accurate estimations under different deflections. The measured results reveal that the blade tip-root distance and blade deflection can be accurately estimated in the complicated and lossy wireless channels around a wind turbine blade. Some future research topics on this application are listed finally. PMID- 26274965 TI - Effect of Television on Obesity and Excess of Weight and Consequences of Health. AB - The epidemic nature of obesity in industrialized countries is a serious health and social concern. The number of obese people has significantly increased in the past 20 years. In Poland excess weight and obesity are a serious epidemiological concern. In terms of the number of overweight people, Poland is a leader in Europe. Therefore, indicating many serious health concerns that are the natural consequences of this phenomenon has become important from the point of view of public health. This work identifies numerous diseases which are a direct consequence of obesity due to bad eating habits and lack of physical exercise among Poles. It discusses the negative effect of television and food commercials contributing to an increase in obesity, not only among adults but also among children. This is an overview forming grounds for further studies into ways of preventing the development of diseases due to obesity, both in Poland and in the world. PMID- 26274966 TI - Association of Mothers' Perception of Neighborhood Quality and Maternal Resilience with Risk of Preterm Birth. AB - We examined the associations of mothers' perception of neighborhood quality and maternal resilience with risk of preterm birth and whether maternal resilience moderated the effect of neighborhood quality perception. We analyzed data from 10,758 women with singleton births who participated in 2010-2012 Los Angeles Mommy and Baby surveys. Multilevel logistic regression models assessed the effects of mothers' perception of neighborhood quality and maternal resilience on preterm birth (yes/no), controlling for potential confounders and economic hardship index, a city-level measure of neighborhood quality. Interaction terms were assessed for moderation. Mothers' perception of neighborhood quality and maternal resilience were each uniquely associated with preterm birth, independent of potential confounders (p-values < 0.05). The risk of preterm birth among mothers who perceived their neighborhood as of poor quality was about 30% greater compared to mothers who perceived their neighborhood as of good quality; the risk was 12% greater among mothers with low resilience compared to those with high resilience. Effects of neighborhood quality were not modified by maternal resilience. The findings suggest that mothers' perception of neighborhood quality and resilience are associated with the risk of preterm birth. Further research should explore whether initiatives aimed at improving neighborhood quality and women's self-esteem may improve birth outcomes. PMID- 26274967 TI - The Level of Self-Esteem and Sexual Functioning in Women with Idiopathic Scoliosis: A Preliminary Study. AB - A person's image, which is determined through physical appearance, considerably affects self-esteem developed from early childhood. Scoliosis causes multiple trunk deformations that can affect a person's perception of the body. The aim of the study was to analyze the impact of scoliosis dimension and the degree of trunk deformation on the level of self-esteem and sexual functioning in women with idiopathic scoliosis. Thirty-six women diagnosed with idiopathic scoliosis were recruited to a prospective, double-blind, randomized controlled trial. The subjects were divided into two groups depending on the value of the Cobb angle. The level of self-esteem was determined by means of the Rosenberg Self-Esteem Scale (SES), whereas the sexual functioning was assessed via the Female Sexual Function Index (FSFI). The trunk deformations were specified with the Posterior Trunk Symmetry Index (POTSI). A statistically significant correlation was proved between the amount of points received in the Rosenberg scale evaluation and the POTSI index in Group A (R = -0.56, p = 0.04). Subjects with smaller deformations within the coronal plane had a higher level of self-confidence. The trunk asymmetries in the coronal plane may have a negative effect on women with scoliosis and their self-appraisal. PMID- 26274968 TI - Dengue Vaccines: A Perspective from the Point of View of Intellectual Property. AB - Dengue is a serious infectious disease and a growing public health problem in many tropical and sub-tropical countries. To control this neglected tropical disease (NTD), vaccines are likely to be the most cost-effective solution. This study analyzed dengue vaccines from both a historical and longitudinal perspective by using patent data, evaluating the geographic and time coverage of innovations, the primary patent holders, the network of cooperation and partnership for vaccine research and development (R & D), the flow of knowledge and the technological domain involved. This study can be seen as an example of the use of patent information to inform policy discussions, strategic research planning, and technology transfer. The results show that 93% of patents were granted since 2000, the majority belonging to the United States and Europe, although the share of patents from developing countries has increased. Unlike another NTDs, there is great participation of private companies in R & D of dengue vaccines and partnerships and collaboration between public and private companies. Finally, in this study, the main holders showed high knowledge absorption and generated capabilities. Therefore, this issue suggests that to overcome the difficulty of translational R & D it is necessary to stimulate the generation of knowledge and relevant scientific research, to enable the productive sector to have the capacity to absorb knowledge, to turn it into innovation, and to articulate partnerships and collaboration. PMID- 26274969 TI - Residents' Waste Separation Behaviors at the Source: Using SEM with the Theory of Planned Behavior in Guangzhou, China. AB - Understanding the factors that affect residents' waste separation behaviors helps in constructing effective environmental campaigns for a community. Using the theory of planned behavior (TPB), this study examines factors associated with waste separation behaviors by analyzing responses to questionnaires distributed in Guangzhou, China. Data drawn from 208 of 1000-field questionnaires were used to assess socio-demographic factors and the TPB constructs (i.e., attitudes, subjective norms, perceived behavioral control, intentions, and situational factors). The questionnaire data revealed that attitudes, subjective norms, perceived behavioral control, intentions, and situational factors significantly predicted household waste behaviors in Guangzhou, China. Through a structural equation modeling analysis, we concluded that campaigns targeting moral obligations may be particularly effective for increasing the participation rate in waste separation behaviors. PMID- 26274970 TI - Seasonal-Spatial Distribution and Long-Term Variation of Transparency in Xin'anjiang Reservoir: Implications for Reservoir Management. AB - Water transparency is a useful indicator of water quality or productivity and is widely used to detect long-term changes in the water quality and eutrophication of lake ecosystems. Based on short-term spatial observations in the spring, summer, and winter and on long-term site-specific observation from 1988 to 2013, the spatial, seasonal, long-term variations, and the factors affecting transparency are presented for Xin'anjiang Reservoir (China). Spatially, transparency was high in the open water but low in the bays and the inflowing river mouths, reflecting the effect of river runoff. The seasonal effects were distinct, with lower values in the summer than in the winter, most likely due to river runoff and phytoplankton biomass increases. The transparency decreased significantly with a linear slope of 0.079 m/year, indicating a 2.05 m decrease and a marked decrease in water quality. A marked increase occurred in chlorophyll a (Chla) concentration, and a significant correlation was found between the transparency and Chla concentration, indicating that phytoplankton biomass can partially explain the long-term trend of transparency in Xin'anjiang Reservoir. The river input and phytoplankton biomass increase were associated with soil erosion and nutrient loss in the catchment. Our study will support future management of water quality in Xin'anjiang Reservoir. PMID- 26274971 TI - Phage PhiPan70, a Putative Temperate Phage, Controls Pseudomonas aeruginosa in Planktonic, Biofilm and Burn Mouse Model Assays. AB - Pseudomonas aeruginosa is one of the Multi-Drug-Resistant organisms most frequently isolated worldwide and, because of a shortage of new antibiotics, bacteriophages are considered an alternative for its treatment. Previously, P. aeruginosa phages were isolated and best candidates were chosen based on their ability to form clear plaques and their host range. This work aimed to characterize one of those phages, PhiPan70, preliminarily identified as a good candidate for phage-therapy. We performed infection curves, biofilm removal assays, transmission-electron-microscopy, pulsed-field-gel-electrophoresis, and studied the in vivo PhiPan70 biological activity in the burned mouse model. PhiPan70 was classified as a member of the Myoviridae family and, in both planktonic cells and biofilms, was responsible for a significant reduction in the bacterial population. The burned mouse model showed an animal survival between 80% and 100%, significantly different from the control animals (0%). However, analysis of the PhiPan70 genome revealed that it was 64% identical to F10, a temperate P. aeruginosa phage. Gene annotation indicated PhiPan70 as a new, but possible temperate phage, therefore not ideal for phage-therapy. Based on this, we recommend genome sequence analysis as an early step to select candidate phages for potential application in phage-therapy, before entering into a more intensive characterization. PMID- 26274973 TI - Dietary Vitamin K Intake Is Associated with Cognition and Behaviour among Geriatric Patients: The CLIP Study. AB - Our objective was to determine whether dietary vitamin K intake was associated with cognition and behavior among older adults. 192 consecutive participants >=65 years, recruited in the cross-sectional CLIP (Cognition and LIPophilic vitamins) study, were separated into two groups according to the tertiles of dietary phylloquinone intake (i.e., lowest third below 207 ug/day versus the other two thirds combined). Daily dietary phylloquinone intake was estimated from 50-item interviewer-administered food frequency questionnaire. Cognition was assessed with Mini-Mental State Examination (MMSE); behaviour with Frontotemporal Behavioral Rating Scale (FBRS). Age, gender, social problems, education, body mass index (BMI), comorbidities, history of stroke, use vitamin K antagonists, inadequate fatty fish intake, serum thyroid-stimulating hormone (TSH), vitamin B12, albumin, and estimated glomerular filtration rate were used as confounders. Compared to participants in the lowest third of dietary phylloquinone intake (n = 64), those with higher intake had higher (i.e., better) mean MMSE score (22.0 +/- 5.7 versus 19.9 +/- 6.2, p = 0.024) and lower (i.e., better) FBRS score (1.5 +/- 1.2 versus 1.9 +/- 1.3, p = 0.042). In multivariate linear regressions, log dietary phylloquinone intake was positively associated with MMSE score (adjusted beta = 1.66, p = 0.013) and inversely associated with FBRS score (adjusted beta = -0.33, p = 0.037). Specifically, log dietary phylloquinone intake correlated negatively with FBRS subscore of physical neglect (r = -0.24, p = 0.001). Higher dietary phylloquinone intake was associated with better cognition and behavior among older adults. PMID- 26274972 TI - Diet-Induced Cognitive Deficits: The Role of Fat and Sugar, Potential Mechanisms and Nutritional Interventions. AB - It is of vital importance to understand how the foods which are making us fat also act to impair cognition. In this review, we compare the effects of acute and chronic exposure to high-energy diets on cognition and examine the relative contributions of fat (saturated and polyunsaturated) and sugar to these deficits. Hippocampal-dependent memory appears to be particularly vulnerable to the effects of high-energy diets and these deficits can occur rapidly and prior to weight gain. More chronic diet exposure seems necessary however to impair other sorts of memory. Many potential mechanisms have been proposed to underlie diet-induced cognitive decline and we will focus on inflammation and the neurotrophic factor, brain-derived neurotrophic factor (BDNF). Finally, given supplementation of diets with omega-3 and curcumin has been shown to have positive effects on cognitive function in healthy ageing humans and in disease states, we will discuss how these nutritional interventions may attenuate diet-induced cognitive decline. We hope this approach will provide important insights into the causes of diet induced cognitive deficits, and inform the development of novel therapeutics to prevent or ameliorate such memory impairments. PMID- 26274975 TI - The Metabolic Fate of Deoxynivalenol and Its Acetylated Derivatives in a Wheat Suspension Culture: Identification and Detection of DON-15-O-Glucoside, 15-Acetyl DON-3-O-Glucoside and 15-Acetyl-DON-3-Sulfate. AB - Deoxynivalenol (DON) is a protein synthesis inhibitor produced by the Fusarium species, which frequently contaminates grains used for human or animal consumption. We treated a wheat suspension culture with DON or one of its acetylated derivatives, 3-acetyl-DON (3-ADON), 15-acetyl-DON (15-ADON) and 3,15 diacetyl-DON (3,15-diADON), and monitored the metabolization over a course of 96 h. Supernatant and cell extract samples were analyzed using a tailored LC-MS/MS method for the quantification of DON metabolites. We report the formation of tentatively identified DON-15-O-beta-D-glucoside (D15G) and of 15-acetyl-DON-3 sulfate (15-ADON3S) as novel deoxynivalenol metabolites in wheat. Furthermore, we found that the recently identified 15-acetyl-DON-3-O-beta-D-glucoside (15-ADON3G) is the major metabolite produced after 15-ADON challenge. 3-ADON treatment led to a higher intracellular content of toxic metabolites after six hours compared to all other treatments. 3-ADON was exclusively metabolized into DON before phase II reactions occurred. In contrast, we found that 15-ADON was directly converted into 15-ADON3G and 15-ADON3S in addition to metabolization into deoxynivalenol-3 O-beta-D-glucoside (D3G). This study highlights significant differences in the metabolization of DON and its acetylated derivatives. PMID- 26274974 TI - Review on Mycotoxin Issues in Ruminants: Occurrence in Forages, Effects of Mycotoxin Ingestion on Health Status and Animal Performance and Practical Strategies to Counteract Their Negative Effects. AB - Ruminant diets include cereals, protein feeds, their by-products as well as hay and grass, grass/legume, whole-crop maize, small grain or sorghum silages. Furthermore, ruminants are annually or seasonally fed with grazed forage in many parts of the World. All these forages could be contaminated by several exometabolites of mycotoxigenic fungi that increase and diversify the risk of mycotoxin exposure in ruminants compared to swine and poultry that have less varied diets. Evidence suggests the greatest exposure for ruminants to some regulated mycotoxins (aflatoxins, trichothecenes, ochratoxin A, fumonisins and zearalenone) and to many other secondary metabolites produced by different species of Alternaria spp. (e.g., AAL toxins, alternariols, tenuazonic acid or 4Z infectopyrone), Aspergillus flavus (e.g., kojic acid, cyclopiazonic acid or beta nitropropionic acid), Aspergillus fuminatus (e.g., gliotoxin, agroclavine, festuclavines or fumagillin), Penicillium roqueforti and P. paneum (e.g., mycophenolic acid, roquefortines, PR toxin or marcfortines) or Monascus ruber (citrinin and monacolins) could be mainly related to forage contamination. This review includes the knowledge of mycotoxin occurrence reported in the last 15 years, with special emphasis on mycotoxins detected in forages, and animal toxicological issues due to their ingestion. Strategies for preventing the problem of mycotoxin feed contamination under farm conditions are discussed. PMID- 26274976 TI - Interleukin 17-Mediated Host Defense against Candida albicans. AB - Candida albicans is part of the normal microbiota in most healthy individuals. However, it can cause opportunistic infections if host defenses are breached, with symptoms ranging from superficial lesions to severe systemic disease. The study of rare congenital defects in patients with chronic mucocutaneous candidiasis led to the identification of interleukin-17 (IL-17) as a key factor in host defense against mucosal fungal infection. Experimental infections in mice confirmed the critical role of IL-17 in mucocutaneous immunity against C. albicans. Research on mouse models has also contributed importantly to our current understanding of the regulation of IL-17 production by different cellular sources and its effector functions in distinct tissues. In this review, we highlight recent findings on IL-17-mediated immunity against C. albicans in mouse and man. PMID- 26274977 TI - Refining Measures for Assessing Problematic/Addictive Digital Gaming Use in Clinical and Research Settings. AB - Problematic or addictive digital gaming (including all types of electronic devices) can and has had extremely adverse impacts on the lives of many individuals across the world. The understanding of this phenomenon, and the effectiveness of treatment design and monitoring, can be improved considerably by continuing refinement of assessment tools. The present article briefly overviews tools designed to measure problematic or addictive use of digital gaming, the vast majority of which are founded on the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for other addictive disorders, such as pathological gambling. Although adapting DSM content and strategies for measuring problematic digital gaming has proven valuable, there are some potential issues with this approach. We discuss the strengths and limitations of current methods for measuring problematic or addictive gaming and provide various recommendations that might help in enhancing or supplementing existing tools, or in developing new and even more effective tools. PMID- 26274978 TI - The Mucosal Immune System of Teleost Fish. AB - Teleost fish possess an adaptive immune system associated with each of their mucosal body surfaces. Evidence obtained from mucosal vaccination and mucosal infection studies reveal that adaptive immune responses take place at the different mucosal surfaces of teleost. The main mucosa-associated lymphoid tissues (MALT) of teleosts are the gut-associated lymphoid tissue (GALT), skin associated lymphoid tissue (SALT), the gill-associated lymphoid tissue (GIALT) and the recently discovered nasopharynx-associated lymphoid tissue (NALT). Teleost MALT includes diffuse B cells and T cells with specific phenotypes different from their systemic counterparts that have co-evolved to defend the microbe-rich mucosal environment. Both B and T cells respond to mucosal infection or vaccination. Specific antibody responses can be measured in the gills, gut and skin mucosal secretions of teleost fish following mucosal infection or vaccination. Rainbow trout studies have shown that IgT antibodies and IgT(+) B cells are the predominant B cell subset in all MALT and respond in a compartmentalized manner to mucosal infection. Our current knowledge on adaptive immunity in teleosts is limited compared to the mammalian literature. New research tools and in vivo models are currently being developed in order to help reveal the great intricacy of teleost mucosal adaptive immunity and help improve mucosal vaccination protocols for use in aquaculture. PMID- 26274979 TI - A Panel of Recombinant Mucins Carrying a Repertoire of Sialylated O-Glycans Based on Different Core Chains for Studies of Glycan Binding Proteins. AB - Sialylated glycans serve as key elements of receptors for many viruses, bacteria, and bacterial toxins. The microbial recognition and their binding specificity can be affected by the linkage of the terminal sugar residue, types of underlying sugar chains, and the nature of the entire glycoconjugate. Owing to the pathobiological significance of sialylated glycans, we have engineered Chinese hamster ovary (CHO) cells to secrete mucin-type immunoglobulin-fused proteins carrying terminal alpha2,3- or alpha2,6-linked sialic acid on defined O-glycan core saccharide chains. Besides stably expressing P-selectin glycoprotein ligand 1/mouse immunoglobulin G2b cDNA (PSGL-1/mIgG2b), CHO cells were stably transfected with plasmids encoding glycosyltransferases to synthesize core 2 (GCNT1), core 3 (B3GNT6), core 4 (GCNT1 and B3GNT6), or extended core 1 (B3GNT3) chains with or without the type 1 chain-encoding enzyme B3GALT5 and ST6GAL1. Western blot and liquid chromatography-mass spectrometry analysis confirmed the presence of core 1, 2, 3, 4, and extended core 1 chains carrying either type 1 (Galb3GlcNAc) or type 2 (Galb4GlcNAc) outer chains with or without alpha2,6 linked sialic acids. This panel of recombinant mucins carrying a repertoire of sialylated O-glycans will be important tools in studies aiming at determining the fine O-glycan binding specificity of sialic acid-specific microbial adhesins and mammalian lectins. PMID- 26274983 TI - Intraoperative MRI for optimizing electrode placement for deep brain stimulation of the subthalamic nucleus in Parkinson disease. AB - OBJECT The degree of clinical improvement achieved by deep brain stimulation (DBS) is largely dependent on the accuracy of lead placement. This study reports on the evaluation of intraoperative MRI (iMRI) for adjusting deviated electrodes to the accurate anatomical position during DBS surgery and acute intracranial changes. METHODS Two hundred and six DBS electrodes were implanted in the subthalamic nucleus (STN) in 110 patients with Parkinson disease. All patients underwent iMRI after implantation to define the accuracy of lead placement. Fifty six DBS electrode positions in 35 patients deviated from the center of the STN, according to the result of the initial postplacement iMRI scans. Thus, we adjusted the electrode positions for placement in the center of the STN and verified this by means of second or third iMRI scans. Recording was performed in adjusted parameters in the x-, y-, and z-axes. RESULTS Fifty-six (27%) of 206 DBS electrodes were adjusted as guided by iMRI. Electrode position was adjusted on the basis of iMRI 62 times. The sum of target coordinate adjustment was -0.5 mm in the x-axis, -4 mm in the y-axis, and 15.5 mm in the z-axis; the total of distance adjustment was 74.5 mm in the x-axis, 88 mm in the y-axis, and 42.5 mm in the z-axis. After adjustment with the help of iMRI, all electrodes were located in the center of the STN. Intraoperative MRI revealed 2 intraparenchymal hemorrhages in 2 patients, brain shift in all patients, and leads penetrating the lateral ventricle in 3 patients. CONCLUSIONS The iMRI technique can guide surgeons as they adjust deviated electrodes to improve the accuracy of implanting the electrodes into the correct anatomical position. The iMRI technique can also immediately demonstrate acute changes such as hemorrhage and brain shift during DBS surgery. PMID- 26274984 TI - Finite element analysis of periventricular lucency in hydrocephalus: extravasation or transependymal CSF absorption? AB - OBJECTIVE: Periventricular lucency (PVL) is often observed in the hydrocephalic brain on CT or MRI. Earlier studies have proposed the extravasation of ventricular CSF into the periventricular white matter or transependymal CSF absorption as possible causes of PVL in hydrocephalus. However, there is insufficient evidence for either theory to be conclusive. METHODS: A finite element (FE) model of the hydrocephalic brain with detailed anatomical geometry was constructed to investigate the possible mechanism of PVL in hydrocephalus. The initiation of hydrocephalus was modeled by applying a transmantle pressure gradient (TPG). The model was exposed to varying TPGs to investigate the effects of different geometrical characteristics on the distribution of PVL. The edema map was derived based on the interstitial pore pressure. RESULTS: The model simulated the main radiological features of hydrocephalus, i.e., ventriculomegaly and PVL. The degree of PVL, assessed by the pore pressure, was prominent in mild to moderate ventriculomegaly. As the degree of ventriculomegaly exceeded certain values, the pore pressure across the cerebrum became positive, thus inducing the disappearance of PVL. CONCLUSIONS: The results are in accordance with common clinical findings of PVL. The degree of ventriculomegaly significantly influences the development of PVL, but two factors were not linearly correlated. The results are indicative of the transependymal CSF absorption as a possible cause of PVL, but the extravasation theory cannot be formally rejected. PMID- 26274980 TI - Complementary LC-MS/MS-Based N-Glycan, N-Glycopeptide, and Intact N-Glycoprotein Profiling Reveals Unconventional Asn71-Glycosylation of Human Neutrophil Cathepsin G. AB - Neutrophil cathepsin G (nCG) is a central serine protease in the human innate immune system, but the importance of its N-glycosylation remains largely undescribed. To facilitate such investigations, we here use complementary LC MS/MS-based N-glycan, N-glycopeptide, and intact glycoprotein profiling to accurately establish the micro- and macro-heterogeneity of nCG from healthy individuals. The fully occupied Asn71 carried unconventional N-glycosylation consisting of truncated chitobiose core (GlcNAcbeta: 55.2%; Fucalpha1,6GlcNAcbeta: 22.7%), paucimannosidic N-glycans (Manbeta1,4GlcNAcbeta1,4GlcNAcbeta: 10.6%; Manbeta1,4GlcNAcbeta1,4(Fucalpha1,6)GlcNAcbeta: 7.9%; Manalpha1,6Manbeta1,4GlcNAcbeta1,4GlcNAcbeta: 3.7%, trace level of Manalpha1,6Manbeta1,4GlcNAcbeta1,4(Fucalpha1,6)GlcNAcbeta), and trace levels of monoantennary alpha2,6- and alpha2,3-sialylated complex N-glycans. High resolution/mass accuracy LC-MS profiling of intact nCG confirmed the Asn71 glycoprofile and identified two C-terminal truncation variants at Arg243 (57.8%) and Ser244 (42.2%), both displaying oxidation of solvent-accessible Met152. Asn71 appeared proximal (~19 A) to the active site of nCG, but due to the truncated nature of Asn71-glycans (~5-17 A) we questioned their direct modulation of the proteolytic activity of the protein. This work highlights the continued requirement of using complementary technologies to accurately profile even relatively simple glycoproteins and illustrates important challenges associated with the analysis of unconventional protein N-glycosylation. Importantly, this study now facilitates investigation of the functional role of nCG Asn71 glycosylation. PMID- 26274985 TI - Prophylactic nimodipine treatment for cochlear and facial nerve preservation after vestibular schwannoma surgery: a randomized multicenter Phase III trial. AB - OBJECTIVE: A pilot study of prophylactic nimodipine and hydroxyethyl starch treatment showed a beneficial effect on facial and cochlear nerve preservation following vestibular schwannoma (VS) surgery. A prospective Phase III trial was undertaken to confirm these results. METHODS: An open-label, 2-arm, randomized parallel group and multicenter Phase III trial with blinded expert review was performed and included 112 patients who underwent VS surgery between January 2010 and February 2013 at 7 departments of neurosurgery to investigate the efficacy and safety of the prophylaxis. The surgery was performed after the patients were randomly assigned to one of 2 groups using online randomization. The treatment group (n = 56) received parenteral nimodipine (1-2 mg/hr) and hydroxyethyl starch (hematocrit 30%-35%) from the day before surgery until the 7th postoperative day. The control group (n = 56) was not treated prophylactically. RESULTS: Intent-to treat analysis showed no statistically significant effects of the treatment on either preservation of facial nerve function (35 [67.3%] of 52 [treatment group] compared with 34 [72.3%] of 47 [control group]) (p = 0.745) or hearing preservation (11 [23.4%] of 47 [treatment group] compared with 15 [31.2%] of 48 [control group]) (p = 0.530) 12 months after surgery. Since tumor sizes were significantly larger in the treatment group than in the control group, logistic regression analysis was required. The risk for deterioration of facial nerve function was adjusted nearly the same in both groups (OR 1.07 [95% CI 0.34-3.43], p = 0.91). In contrast, the risk for postoperative hearing loss was adjusted 2 times lower in the treatment group compared with the control group (OR 0.49 [95% CI 0.18-1.30], p = 0.15). Apart from dose-dependent hypotension (p < 0.001), no clinically relevant adverse reactions were observed. CONCLUSIONS: There were no statistically significant effects of the treatment. Despite the width of the confidence intervals, the odds ratios may suggest but do not prove a clinically relevant effect of the safe study medication on the preservation of cochlear nerve function after VS surgery. Further study is needed before prophylactic nimodipine can be recommended in VS surgery. PMID- 26274986 TI - Anatomy and approaches along the cerebellar-brainstem fissures. AB - OBJECT Fissure dissection is routinely used in the supratentorial region to access deeply situated pathology while minimizing division of neural tissue. Use of fissure dissection is also practical in the posterior fossa. In this study, the microsurgical anatomy of the 3 cerebellar-brainstem fissures (cerebellomesencephalic, cerebellopontine, and cerebellomedullary) and the various procedures exposing these fissures in brainstem surgery were examined. METHODS Seven cadaveric heads were examined with a microsurgical technique and 3 with fiber dissection to clarify the anatomy of the cerebellar-brainstem and adjacent cerebellar fissures, in which the major vessels and neural structures are located. Several approaches directed along the cerebellar surfaces and fissures, including the supracerebellar infratentorial, occipital transtentorial, retrosigmoid, and midline suboccipital approaches, were examined. The 3 heads examined using fiber dissection defined the anatomy of the cerebellar peduncles coursing in the depths of these fissures. RESULTS Dissections directed along the cerebellar-brainstem and cerebellar fissures provided access to the posterior and posterolateral midbrain and upper pons, lateral pons, floor and lateral wall of the fourth ventricle, and dorsal and lateral medulla. CONCLUSIONS Opening the cerebellar-brainstem and adjacent cerebellar fissures provided access to the brainstem surface hidden by the cerebellum, while minimizing division of neural tissue. Most of the major cerebellar arteries, veins, and vital neural structures are located in or near these fissures and can be accessed through them. PMID- 26274987 TI - Morbidity and mortality of patients with endovascularly treated intracerebral aneurysms: does physician specialty matter? AB - OBJECT Endovascular treatment of cerebrovascular pathology, particularly aneurysms, is becoming more prevalent. There is a wide variety in clinical background and training of physicians who treat cerebrovascular pathology through endovascular means. The impact of clinical training background on patient outcomes is not well documented. METHODS The authors conducted a retrospective analysis of a large national database, the University HealthSystem Consortium, that was queried in the years 2009-2013. Cases of both unruptured cerebral aneurysms and subarachnoid hemorrhage treated by endovascular obliteration were studied. Outcome measures of morbidity and mortality were evaluated according to the specialty of the treating physician. RESULTS Elective embolization of an unruptured aneurysm was the procedure code and primary diagnosis, respectively, for 12,400 cases. Patients with at least 1 complication were reported in 799 cases (6.4%). Deaths were reported in 193 cases (1.6%). Complications and deaths were varied by specialty; the highest incidence of complications (11.1%) and deaths (3.0%) were reported by neurologists. The fewest complications were reported by neurosurgeons (5.4%; 1.4% deaths), with a higher incidence of complications reported in cases performed by neurologists (p < 0.0001 for both complications and deaths) and to a lesser degree interventional radiologists (p = 0.0093 for complications). Subarachnoid hemorrhage was the primary diagnosis and procedure for 8197 cases. At least 1 complication was reported in 2385 cases (29%) and deaths in 983 cases (12%). The number of complications and deaths varied among specialties. The highest incidence of complications (34%) and deaths (13.5%) in subarachnoid hemorrhage was in cases performed by neurologists. The fewest complications were in cases by neurosurgeons (27%), with a higher incidence of complications in cases performed by neurologists (34%, p < 0.0001), and a trend of increased complications with interventional radiologists (30%, p < 0.0676). The lowest incidence of mortality was in cases performed by neurosurgeons (11.5%), with a significantly higher incidence of mortality in cases performed by neurologists (13.5%, p = 0.0372). Mortality rates did not reach statistical significance with respect to interventional radiologists (12.1%, p = 0.4884). CONCLUSIONS Physicians of varied training types and backgrounds use endovascular treatment of ruptured and unruptured intracerebral aneurysms. In this study there was a statistically significant finding that neurosurgically trained physicians may demonstrate improved outcomes with respect to endovascular treatment of unruptured aneurysms in this cohort. This finding warrants further investigation. PMID- 26274988 TI - Motor cortex stimulation and neuropathic pain: how does motor cortex stimulation affect pain-signaling pathways? AB - OBJECTIVE: Neuropathic pain is often severe. Motor cortex stimulation (MCS) is used for alleviating neuropathic pain, but the mechanism of action is still unclear. This study aimed to understand the mechanism of action of MCS by investigating pain-signaling pathways, with the expectation that MCS would regulate both descending and ascending pathways. METHODS: Neuropathic pain was induced in Sprague-Dawley rats. Surface electrodes for MCS were implanted in the rats. Tactile allodynia was measured by behavioral testing to determine the effect of MCS. For the pathway study, immunohistochemistry was performed to investigate changes in c-fos and serotonin expression; micro-positron emission tomography (mPET) scanning was performed to investigate changes of glucose uptake; and extracellular electrophysiological recordings were performed to demonstrate brain activity. RESULTS: MCS was found to modulate c-fos and serotonin expression. In the mPET study, altered brain activity was observed in the striatum, thalamic area, and cerebellum. In the electrophysiological study, neuronal activity was increased by mechanical stimulation and suppressed by MCS. After elimination of artifacts, neuronal activity was demonstrated in the ventral posterolateral nucleus (VPL) during electrical stimulation. This neuronal activity was effectively suppressed by MCS. CONCLUSIONS: This study demonstrated that MCS effectively attenuated neuropathic pain. MCS modulated ascending and descending pain pathways. It regulated neuropathic pain by affecting the striatum, periaqueductal gray, cerebellum, and thalamic area, which are thought to regulate the descending pathway. MCS also appeared to suppress activation of the VPL, which is part of the ascending pathway. PMID- 26274989 TI - Editorial: Radial nerve. PMID- 26274990 TI - Editorial: Deep brain stimulation and intraoperative MRI. PMID- 26274991 TI - Benign meningiomas (WHO Grade I) with atypical histological features: correlation of histopathological features with clinical outcomes. AB - OBJECT World Health Organization (WHO) Grade I (benign) meningiomas with atypical features may behave more aggressively than similarly graded tumors without atypical features. Here, the prognostic significance of atypical features in benign meningiomas was determined. METHODS Data from patients diagnosed with WHO Grade I benign meningiomas per the 2007 WHO criteria and who underwent surgery between 2002 and 2012 were retrospectively reviewed. Patients were stratified by the absence or presence of 1 to 2 atypical features with review of the clinical and histological factors. RESULTS A total of 148 patients met the inclusion criteria (n = 77 with atypia; n = 71 without atypia). The median follow-up duration after pathological diagnosis was 37.5 months. Thirty patients had progression/recurrence (P/R) after initial treatment, and 22 (73%) of 30 patients with P/R had 1-2 atypical features. The presence of atypical features was significantly associated with P/R (p = 0.03) and independent of the MIB-1 labeling index. The 1-year and 5-year actuarial rates of P/R were 9.6% versus 1.4% and 30.8% versus 13.8% fortumors with and without atypical features, respectively. Higher Simpson grade resection (II-IV vs I) was associated with the increased risk of P/R (p < 0.001). Stratification of patients into low-risk (Simpson Grade I), intermediate-risk (Simpson Grade II-IV with no atypical features), and high-risk groups (Simpson Grade II-IV with atypical features) was significantly correlated with increased risk of P/R (p < 0.001). CONCLUSIONS Patients with benign meningiomas with atypical features and those undergoing Simpson Grade II-IV resection are at significantly increased risk of P/R. Patients with these features may benefit from the consideration of additional surgery and/or radiation therapy. PMID- 26274992 TI - Endoscope-assisted endonasal versus supraorbital keyhole resection of olfactory groove meningiomas: comparison and combination of 2 minimally invasive approaches. AB - OBJECTIVE: Although the endonasal endoscopic approach has been applied to remove olfactory groove meningiomas, controversy exists regarding the efficacy and safety of this approach compared with more traditional transcranial approaches. The endonasal endoscopic approach was compared with the supraorbital (eyebrow) keyhole technique, as well as a combined "above-and-below" approach, to evaluate the relative merits of each approach in different situations. METHODS: Nineteen cases were reviewed and divided according to operative technique into 3 different groups: purely endonasal (6 cases); supraorbital eyebrow (microscopic with endoscopic assistance; 7 cases); and combined endonasal endoscopic with either the bicoronal or eyebrow microscopic approach (6 cases). Resection was judged on postoperative MRI using volumetric analysis. Tumors were assessed based on the Mohr radiological classification and the presence of the lion's mane sign. RESULTS: The mean age at surgery was 61.4 years. The mean tumor volume was 19.6 cm(3) in the endonasal group, 33.5 cm(3) in the supraorbital group, and 37.8 cm(3) in the combined group. Significant frontal lobe edema was identified in 10 cases (52.6%). The majority of tumors were either Mohr Grade II (moderate) (42.1%) or Grade III (large) (47.4%). Gross-total resection was achieved in 50% of the endonasal cases, 100% of the supraorbital eyebrow cases with endoscopic assistance, and 66.7% of the combined cases. The extent of resection was 87.8% for the endonasal cases, 100% for the supraorbital eyebrow cases, and 98.9% for the combined cases. Postoperative anosmia occurred in 100% of the endonasal and combined cases and only 57.1% of the supraorbital eyebrow cases. Excluding anosmia, permanent complications occurred in 83.3% of the cases in the endoscopic group, 0% of the cases in the supraorbital eyebrow group, and 16.7% of cases in the combined group (p = 0.017). There were 3 tumor recurrences: 2 in the endonasal group and 1 in the combined group. CONCLUSIONS: The supraorbital eyebrow approach, with endoscopic assistance, leads to a higher extent of resection and lower rate of complications than the purely endonasal endoscopic approach. The endonasal endoscopic approach by itself may be suitable for a small percentage of cases. The combined above-and-below approaches are useful for large tumors with invasion of the ethmoid sinuses. PMID- 26274993 TI - Anaplastic meningioma: octreotide therapy for a case of recurrent and progressive intracranial disease. AB - Meningiomas are common intracranial tumors categorized as Grades I-III per the current WHO guidelines. A small percentage of meningiomas are Grades II and III, which are likely to recur after initial treatment. Grade III meningiomas are considered to be malignant and warrant aggressive management. If surgery and radiation fail to produce lasting remission, effective treatment options for patients with progressive anaplastic meningiomas are elusive. The authors present the case of a patient with a meningioma that gradually progressed from Grade I to Grade III over 12 years despite repeated surgery and radiation therapy. The patient has been in remission for over 3 years following octreotide therapy. PMID- 26274994 TI - The War of Independence: a surgical algorithm for the treatment of head injury in the continental army. AB - The American Revolution was a gruesome warthat resulted in the independence of the United States of America from the British crown and countless casualties to both belligerents. However, from these desperate times, the treatment of traumatic head injury was elucidated, as were the origins of American neurosurgery in the 18th century. During the war, the surgical manual used by military field surgeons was titled Plain Concise Practical Remarks on the Treatment of Wounds and Fractures, by Dr. John Jones. This manual explains the different types of cranial injuries understood at that time as well as the relevant surgical treatment. This article seeks to review the surgical treatment of head injury in the Revolutionary War as outlined by Dr. Jones's manual. PMID- 26274995 TI - Height of aneurysm neck and estimated extent of brain retraction: powerful predictors of olfactory dysfunction after surgery for unruptured anterior communicating artery aneurysms. AB - OBJECTIVE: The highest incidence of olfactory dysfunction following a pterional approach and its modifications for an intracranial aneurysm has been reported in cases of anterior communicating artery (ACoA) aneurysms. The radiological characteristics of unruptured ACoA aneurysms affecting the extent of retraction of the frontal lobe and olfactory nerve were investigated as risk factors for postoperative olfactory dysfunction. METHODS: A total of 102 patients who underwent a pterional or superciliary keyhole approach to clip an unruptured ACoA aneurysm from 2006 to 2013 were included in this study. Those patients who complained of permanent olfactory dysfunction after their aneurysm surgery, during a postoperative office visit or a telephone interview, were invited to undergo an olfactory test, the Korean version of the Sniffin' Sticks test. In addition, the angiographic characteristics of ACoA aneurysms, including the maximum diameter, the projecting direction of the aneurysm, and the height of the neck of the aneurysm, were all recorded based on digital subtraction angiography and sagittal brain images reconstructed using CT angiography. Furthermore, the extent of the brain retraction was estimated based on the height of the ACoA aneurysm neck. RESULTS: Eleven patients (10.8%) exhibited objective olfactory dysfunction in the Sniffin' Sticks test, among whom 9 were anosmic and 2 were hyposmic. Univariate and multivariate analyses revealed that the direction of the ACoA aneurysm, ACoA aneurysm neck height, and estimated extent of brain retraction were statistically significant risk factors for postoperative olfactory dysfunction. Based on a receiver operating characteristic (ROC) analysis, an ACoA aneurysm neck height > 9 mm and estimated brain retraction > 12 mm were chosen as the optimal cutoff values for differentiating anosmic/hyposmic from normosmic patients. The values for the area under the ROC curves were 0.939 and 0.961, respectively. CONCLUSIONS: In cases of unruptured ACoA aneurysm surgery, the height of the aneurysm neck and the estimated extent of brain retraction were both found to be powerful predictors of the occurrence of postoperative olfactory dysfunction. PMID- 26274996 TI - Toxic levels of ammonia in human brain abscess. AB - OBJECTIVE: Brain abscesses could lead to cerebral symptoms through tissue destruction, edema, changes in brain architecture, and increased intracranial pressure. However, the possibility that the pus itself could contribute to symptoms has received little attention. Brain abscesses are areas of tissue destruction, proteolysis, and formation of free amino acids, which are energy substrates for bacteria and possible sources of ammonia. Ammonia is neurotoxic, may cause brain edema, and could contribute to the symptoms of brain abscesses. METHODS: The authors analyzed the extracellular phase of pus from 14 patients with brain abscesses with respect to ammonia and amino acids. For comparison, CSF from 10 patients undergoing external ventricular drainage was included. The ammonia-forming ability of Streptococcus intermedius and Staphylococcus aureus, two common microbial isolates in brain abscesses, was studied in vitro. RESULTS: In brain abscesses ammonia was 15.5 mmol/L (median value; range 1.7-69.2 mmol/L). In CSF ammonia was 29 MUmol/L (range 17-55 MUmol/L; difference from value in pus: p < 0.001). The total concentration of amino acids in brain abscesses was 1.12-16 times higher than the ammonia concentration (p = 0.011). The median glucose value in pus was 0 mmol/L (range 0-2.1 mmol/L), lactate was 21 mmol/L (range 3.3-26.5 mmol/L), and pH was 6.8 (range 6.2-7.3). In vitro, S. intermedius and S. aureus formed ammonia at 6-7 mmol/L in 24 hours when incubated with 20 proteinogenic amino acids plus g-aminobutyric acid (GABA), taurine, and glutathione at 1 mmol/L. CONCLUSIONS: Intracerebral abscesses contain toxic levels of ammonia. At the concentrations found in pus, ammonia could contribute to the brain edema and the symptoms of brain abscesses. PMID- 26274997 TI - Laser speckle imaging to improve clinical outcomes for patients with trigeminal neuralgia undergoing radiofrequency thermocoagulation. AB - OBJECTIVE: Percutaneous treatments for trigeminal neuralgia are safe, simple, and effective for achieving good pain control. Procedural risks could be minimized by using noninvasive imaging techniques to improve the placement of the radiofrequency thermocoagulation probe into the trigeminal ganglion. Positioning of a probe is crucial to maximize pain relief and to minimize unwanted side effects, such as denervation in unaffected areas. This investigation examined the use of laser speckle imaging during probe placement in an animal model. METHODS: This preclinical safety study used nonhuman primates, Macaca nemestrina (pigtail monkeys), to examine whether real-time imaging of blood flow in the face during the positioning of a coagulation probe could monitor the location and guide the positioning of the probe within the trigeminal ganglion. RESULTS: Data from 6 experiments in 3 pigtail monkeys support the hypothesis that laser imaging is safe and improves the accuracy of probe placement. CONCLUSIONS: Noninvasive laser speckle imaging can be performed safely in nonhuman primates. Because improved probe placement may reduce morbidity associated with percutaneous rhizotomies, efficacy trials of laser speckle imaging should be conducted in humans. PMID- 26274998 TI - Results of nerve grafting in radial nerve injuries occurring proximal to the humerus, including those within the posterior cord. AB - OBJECT Results of radial nerve grafting are largely unknown for lesions of the radial nerve that occur proximal to the humerus, including those within the posterior cord. METHODS The authors describe 13 patients with proximal radial nerve injuries who were surgically treated and then followed for at least 24 months. The patients' average age was 26 years and the average time between accident and surgery was 6 months. Sural nerve graft length averaged 12 cm. Recovery was scored according to the British Medical Research Council (BMRC) scale, which ranges from M0 to M5 (normal muscle strength). RESULTS After grafting, all 7 patients with an elbow extension palsy recovered elbow extension, scoring M4. Six of the 13 recovered M4 wrist extension, 6 had M3, and 1 had M2. Thumb and finger extension was scored M4 in 3 patients, M3 in 2, M2 in 2, and M0 in 6. CONCLUSIONS The authors consider levels of strength of M4 for elbow and wrist extension and M3 for thumb and finger extension to be good results. Based on these criteria, overall good results were obtained in only 5 of the 13 patients. In proximal radial nerve lesions, the authors now advocate combining nerve grafts with nerve or tendon transfers to reconstruct wrist, thumb, and finger extension. PMID- 26274999 TI - Increased level of H19 long noncoding RNA promotes invasion, angiogenesis, and stemness of glioblastoma cells. AB - OBJECT Increased levels of H19 long noncoding RNA (lncRNA) have been observed in many cancers, suggesting that overexpression of H19 may be important in the development of carcinogenesis. However, the role of H19 in human glioblastoma is still unclear. The object of this study was to examine the level of H19 in glioblastoma samples and investigate the role of H19 in glioblastoma carcinogenesis. METHODS Glioblastoma and nontumor brain tissue specimens were obtained from tissue obtained during tumor resection in 30 patients with glioblastoma. The level of H19 lncRNA was detected by real-time quantitative reverse transcription polymerase chain reaction. The role of H19 in invasion, angiogenesis, and stemness of glioblastoma cells was then investigated using commercially produced cell lines (U87 and U373). The effects of H19 overexpression on glioblastoma cell invasion and angiogenesis were detected by in vitro Matrigel invasion and endothelial tube formation assay. The effects of H19 on glioblastoma cell stemness and tumorigenicity were investigated by neurosphere formation and an in vivo murine xenograft model. RESULTS The authors found that H19 is significantly overexpressed in glioblastoma tissues, and the level of expression was associated with patient survival. In the subsequent investigations, the authors found that overexpression of H19 promotes glioblastoma cell invasion and angiogenesis in vitro. Interestingly, H19 was also significantly overexpressed in CD133(+) glioblastoma cells, and overexpression of H19 was associated with increased neurosphere formation of glioblastoma cells. Finally, stable overexpression of H19 was associated with increased tumor growth in the murine xenograft model. CONCLUSIONS The results of this study suggest that increased expression of H19 lncRNA promotes invasion, angiogenesis, stemness, and tumorigenicity of glioblastoma cells. Taken together, these findings indicate that H19 plays an important role in tumorigenicity and stemness of glioblastoma and thus could be a therapeutic target for treatment of glioblastoma in the future. PMID- 26275000 TI - Lateral supracerebellar infratentorial approach for microsurgical resection of large midline pineal region tumors: techniques to expand the operative corridor. AB - Pineal region tumors pose certain challenges in regard to their resection: a deep surgical field, associated critical surrounding neurovascular structures, and narrow operative working corridor due to obstruction by the apex of the culmen. The authors describe a lateral supracerebellar infratentorial approach that was successfully used in the treatment of 10 large (> 3 cm) midline pineal region tumors. The patients were placed in a modified lateral decubitus position. A small lateral suboccipital craniotomy exposed the transverse sinus. Tentorial retraction sutures were used to gently rotate and elevate the transverse sinus to expand the lateral supracerebellar operative corridor. This approach placed only unilateral normal structures at risk and minimized vermian venous sacrifice. The surgeon achieved generous exposure of the caudal midline mesencephalon through a "cross-court" oblique trajectory, while avoiding excessive retraction on the culmen. All patients underwent the lateral approach with no approach-related complication. The final pathological diagnoses were consistent with meningioma in 3 cases, pilocytic astrocytoma in 3 cases, intermediate grade pineal region tumor in 2 cases, and pineoblastoma in 2 cases. The entire extent of these tumors was readily reachable through the lateral supracerebellar route. Gross-total resection was achieved in 8 (80%) of the 10 cases; in 2 cases (20%) near-total resection was performed due to adherence of these tumors to deep diencephalic veins. Large midline pineal region tumors can be removed through a unilateral paramedian suboccipital craniotomy. This approach is simple, may spare some of the midline vermian bridging veins, and may be potentially less invasive and more efficient. PMID- 26275001 TI - Editorial: Discipline and training. PMID- 26275002 TI - Editorial: Does physician specialty matter? PMID- 26275003 TI - Postoperative subdural hygroma and chronic subdural hematoma after unruptured aneurysm surgery: age, sex, and aneurysm location as independent risk factors. AB - OBJECTIVE: This study investigated the incidence and risk factors for the postoperative occurrence of subdural complications, such as a subdural hygroma and resultant chronic subdural hematoma (CSDH), following surgical clipping of an unruptured aneurysm. The critical age affecting such occurrences and follow-up results were also examined. METHODS: The case series included 364 consecutive patients who underwent aneurysm clipping via a pterional or superciliary keyhole approach for an unruptured saccular aneurysm in the anterior cerebral circulation between 2007 and 2013. The subdural hygromas were identified based on CT scans 6 9 weeks after surgery, and the volumes were measured using volumetry studies. Until their complete resolution, all the subdural hygromas were followed using CT scans every 1-2 months. Meanwhile, the CSDHs were classified as nonoperative or operative lesions that were treated by bur-hole drainage. The age and sex of the patients, aneurysm location, history of a subarachnoid hemorrhage (SAH), and surgical approach (pterional vs superciliary) were all analyzed regarding the postoperative occurrence of a subdural hygroma or CSDH. The follow-up results of the subdural complications were also investigated. RESULTS: Seventy patients (19.2%) developed a subdural hygroma or CSDH. The results of a multivariate analysis showed that advanced age (p = 0.003), male sex (p < 0.001), middle cerebral artery (MCA) aneurysm (p = 0.045), and multiple concomitant aneurysms at the MCA and anterior communicating artery (ACoA) (p < 0.001) were all significant risk factors of a subdural hygroma and CSDH. In addition, a receiver operating characteristic (ROC) curve analysis revealed a cut-off age of > 60 years, which achieved a 70% sensitivity and 69% specificity with regard to predicting such subdural complications. The female patients <= 60 years of age showed a negligible incidence of subdural complications for all aneurysm groups, whereas the male patients > 60 years of age showed the highest incidence of subdural complications at 50%-100%, according to the aneurysm location. The subdural hygromas detected 6-9 weeks postoperatively showed different follow-up results, according to the severity. The subdural hygromas that converted to a CSDH were larger in volume than the subdural hygromas that resolved spontaneously (28.4 +/- 16.8 ml vs 59.6 +/- 38.4 ml, p = 0.003). Conversion to a CSDH was observed in 31.3% (5 of 16), 64.3% (9 of 14), and 83.3% (5 of 6) of the patients with mild, moderate, and severe subdural hygromas, respectively. CONCLUSIONS: Advanced age, male sex, and an aneurysm location requiring extensive arachnoid dissection (MCA aneurysms and multiple concomitant aneurysms at the MCA and ACoA) are all correlated with the occurrence of a subdural hygroma and CSDH after unruptured aneurysm surgery. The critical age affecting such an occurrence is 60 years. PMID- 26275004 TI - A Novel Culture Model for Human Pluripotent Stem Cell Propagation on Gelatin in Placenta-conditioned Media. AB - The propagation of human pluripotent stem cells (hPSCs) in conditioned medium derived from human cells in feeder-free culture conditions has been of interest. Nevertheless, an ideal humanized ex vivo feeder-free propagation method for hPSCs has not been developed; currently, additional exogenous substrates including basic fibroblast growth factor (bFGF), a master hPSC-sustaining factor, is added to all of culture media and synthetic substrata such as Matrigel or laminin are used in all feeder-free cultures. Recently, our group developed a simple and efficient protocol for the propagation of hPSCs using only conditioned media derived from the human placenta on a gelatin-coated dish without additional exogenous supplementation or synthetic substrata specific to hPSCs. This protocol has not been reported previously and might enable researchers to propagate hPSCs efficiently in humanized culture conditions. Additionally, this model obviates hPSC contamination risks by animal products such as viruses or unknown proteins. Furthermore, this system facilitates easy mass production of hPSCs using the gelatin coating, which is simple to handle, dramatically decreases the overall costs of ex vivo hPSC maintenance. PMID- 26275005 TI - Betrayal trauma and child symptoms: The role of emotion. AB - Both mothers' and children's exposures to interpersonal violence-including betrayal traumas-are linked with heightened risk for children developing internalizing and externalizing symptoms. Despite this association, little research has examined additional factors that may explain this risk, such as emotion skills. The current study examined the relationship between mother-child emotion understanding abilities and use of emotion language on a behavioral facial affect perception task and betrayal trauma exposure in relation to child internalizing/externalizing symptoms. The sample included 47 ethnically diverse female guardians (ages 25-51 years old; M age = 37.7) and their children (ages 7 11 years old; M age = 9.1). Results indicated that maternal provision of a spontaneous, unprompted reason for emotions during the facial affect perception task was significantly associated with lower child internalizing/externalizing symptoms when both mothers' and children's betrayal trauma histories were controlled. The results suggest that emotion skills (in particular, the way mothers talk about emotions) warrant greater attention in research on the development of child internalizing/externalizing problems. PMID- 26275007 TI - Prophylactic bilateral salpingectomy for the prevention of ovarian cancers: What is happening in Italy? AB - In 2011, the Society of Gynecologic Oncology of Canada encouraged physicians to discuss with their patients the risks and benefits of prophylactic bilateral salpingectomy (PBS) at the time of hysterectomy or tubal ligation for prevention of ovarian cancers (OCs). The aim of this study was to examine obstetrician gynaecologists' knowledge, opinions and practice patterns relating to opportunistic salpingectomy in the general population. An anonymous electronic survey was sent to residents, academic and hospital staff in Italian OBGYN departments. The survey included questions on demographics, knowledge and attitudes in terms of the implementation of PBS in women at average population risk of OC. At least 80% of the 479 respondents reported performing PBS during hysterectomy for benign indications, chiefly with the intent of OC risk reduction but also to decrease the risk of reoperation and subsequent tubal pathologies. Among the 86 colleagues who do not routinely perform PBS, more than 50% stated that they have doubts regarding the benefits associated with the procedure. Most of the respondents declared that they were familiar with the literature on the topic and were aware of the data reporting the safety of the procedure, and only 21 (4.53%) had never heard of PBS. Over 40% of the respondents worked in hospitals in southern Italy. PBS as a prophylactic measure to reduce the incidence of OC is a well-known strategy among the Italian OBGYNs interviewed. Given the unequal distribution of respondents, however, wider educational initiatives should be undertaken, at least in Italy, to increase the implementation of salpingectomy among OBGYNs. PMID- 26275006 TI - Mouthwash use and cancer of the head and neck: a pooled analysis from the International Head and Neck Cancer Epidemiology Consortium. AB - Most mouthwashes contain alcohol, a known cause of head and neck cancer (oral cavity, pharynx, larynx), likely through the carcinogenic activity of acetaldehyde, formed in the oral cavity from alcohol. We carried out a pooled analysis of 8981 cases of head and neck cancer and 10 090 controls from 12 case control studies with comparable information on mouthwash use in the International Head and Neck Cancer Epidemiology Consortium. Logistic regression was used to assess the association of mouthwash use with cancers of the oral cavity, oropharynx, hypopharynx, and larynx, adjusting for study, age, sex, pack-years of tobacco smoking, number of alcoholic drinks/day, and education. Compared with never users of mouthwash, the odds ratio (OR) of all head and neck cancers was 1.01 [95% confidence interval (CI): 0.94-1.08] for ever users, based on 12 studies. The corresponding ORs of cancer of the oral cavity and oropharynx were 1.11 (95% CI: 1.00-1.23) and 1.28 (95% CI: 1.06-1.56), respectively. OR for all head and neck cancer was 1.15 (95% CI: 1.01-1.30) for use for more than 35 years, based on seven studies (P for linear trend=0.01), and OR 1.31 (95% CI: 1.09-1.58) for use more than one per day, based on five studies (P for linear trend <0.001). Although limited by the retrospective nature of the study and the limited ability to assess risks of mouthwash use in nonusers of tobacco and alcohol, this large investigation shows potential risks for head and neck cancer subsites and in long term and frequent users of mouthwash. This pooled analysis provides the most precise estimate of the association between mouthwash use and head and neck cancer. PMID- 26275009 TI - A two-phase approach to Fourier transform ion mobility time-of-flight mass spectrometry. AB - It is well known that the duty cycle of common drift-tube ion mobility experiments is often below 1%. However, multiplexing approaches such as Fourier and Hadamard pulsing schemes have been shown to independently enhance the throughput of ion mobility spectrometry (IMS) experiments to levels that approach 50%. While challenges remain to their broad scale implementation we describe a new Fourier transform (FT) IMS experiment that is directly compatible with standard drift tube ion mobility mass spectrometers (DT-IMMS). Compared to previous FT-IMS experiments, our new approach requires only a single gate and circumvents the need for signal apodization by combining data from two frequency pulsing sequences 180 degrees out of phase. Assessment of our initial results highlights an increase in signal-to-noise (SNR) relative to both previous implementations FT-IMS experiments and signal averaged (SA) experiments. For select tetraalkylammonium salts SNR improvements of more than one order of magnitude are routinely possible. To explore the performance metrics associated with the technique a number of experimental variables were systematically altered including frequency sweep range, sweep time, and data acquisition time. Using this experimental design we present the key aspects, considerations, and minimum resources necessary for other IMS researchers to incorporate this operational mode into their research. The two-phase FT-IMMS technique offers a tractable mechanism to enhance sensitivity for IMMS measurements and its broad-scale adoption by IMMS researchers promises to enhance the acquisition speed for mobility measurements using hybrid instrumentation. PMID- 26275010 TI - A Brief History of the Perioperative Surgical Home. PMID- 26275011 TI - Kidney Regeneration in Adult Zebrafish by Gentamicin Induced Injury. AB - The kidney is essential for fluid homeostasis, blood pressure regulation and filtration of waste from the body. The fundamental unit of kidney function is the nephron. Mammals are able to repair existing nephrons after injury, but lose the ability to form new nephrons soon after birth. In contrast to mammals, adult fish produce new nephrons (neonephrogenesis) throughout their lives in response to growth requirements or injury. Recently, lhx1a has been shown to mark nephron progenitor cells in the adult zebrafish kidney, however mechanisms controlling the formation of new nephrons after injury remain unknown. Here we show our method for robust and reproducible injury in the adult zebrafish kidney by intraperitoneal (i.p.) injection of gentamicin, which uses a noninvasive visual screening process to select for fish with strong but nonlethal injury. Using this method, we can determine optimal gentamicin dosages for injury and go on to demonstrate the effect of higher temperatures on kidney regeneration in zebrafish. PMID- 26275012 TI - Symbolic representation of propulsion cycles in manual wheelchair locomotion. PMID- 26275013 TI - Correction: Genome-Wide Analyses Reveal a Role for Peptide Hormones in Planarian Germline Development. PMID- 26275014 TI - Normothermic Ex Vivo Kidney Perfusion for the Preservation of Kidney Grafts prior to Transplantation. AB - Kidney transplantation has become a well-established treatment option for patients with end-stage renal failure. The persisting organ shortage remains a serious problem. Therefore, the acceptance criteria for organ donors have been extended leading to the usage of marginal kidney grafts. These marginal organs tolerate cold storage poorly resulting in increased preservation injury and higher rates of delayed graft function. To overcome the limitations of cold storage, extensive research is focused on alternative normothermic preservation methods. Ex vivo normothermic organ perfusion is an innovative preservation technique. The first experimental and clinical trials for ex vivo lung, liver, and kidney perfusions demonstrated favorable outcomes. In addition to the reduction of cold ischemic injury, the method of normothermic kidney storage offers the opportunity for organ assessment and repair. This manuscript provides information about kidney retrieval, organ preservation techniques, and isolated ex vivo normothermic kidney perfusion (NEVKP) in a porcine model. Surgical techniques, set up for the perfusion solution and the circuit, potential assessment options, and representative results are demonstrated. PMID- 26275016 TI - Multiple and solitary skeletal muscle metastases on 18F-FDG PET/CT imaging. AB - OBJECTIVE: The aim of this study was to investigate the features and patterns of skeletal muscle metastases (SMM) detected with F-fluorodeoxyglucose (F-FDG) PET/computed tomography (PET/CT). PARTICIPANTS AND METHODS: Our database was analyzed for patients with pathologically proven malignancy, who underwent F-FDG PET/CT in our institution. The patients with SMM were included in the study group on the basis of the final diagnosis confirmed by follow-up or histopathology. Images were acquired using a PET/CT system Biograph mCT S(64)-4R. CT was performed without contrast enhancement. RESULTS: The selected group included 31 patients (1.7% of the database, which consisted of 1805 patients). A total of 233 lesions were found. The prevalence of SMM evaluated in specific primary malignancies was the highest in melanoma (6.9%), followed by carcinoma of unknown primary (4.4%), colorectal cancer (4.1%) and lung cancer (2.8%). Three patterns of skeletal muscle metastatic involvement were observed: multiple SMM accompanied by other metastases (64.5%), solitary lesion associated with other metastases (29%) and isolated intramuscular lesions (two cases, 6.5%). Isolated SMM represented recurrence of the malignant disease. In patients with extraskeletal metastases, solitary or multiple SMM did not affect tumor staging. CONCLUSION: Solitary SMM are less common than multiple on F-FDG PET/CT imaging. SMM are usually associated with other metastases and do not affect tumor staging. The cases of isolated SMM are very rare. Nevertheless, in patients with a diagnosis of malignant disease, a solitary, F-FDG avid intramuscular focus should be suspected to represent metastasis. PMID- 26275015 TI - Derivation of Adult Human Fibroblasts and their Direct Conversion into Expandable Neural Progenitor Cells. AB - Generation of induced pluripotent stem cell (iPSCs) from adult skin fibroblasts and subsequent differentiation into somatic cells provides fascinating prospects for the derivation of autologous transplants that circumvent histocompatibility barriers. However, progression through a pluripotent state and subsequent complete differentiation into desired lineages remains a roadblock for the clinical translation of iPSC technology because of the associated neoplastic potential and genomic instability. Recently, we and others showed that somatic cells cannot only be converted into iPSCs but also into different types of multipotent somatic stem cells by using defined factors, thereby circumventing progression through the pluripotent state. In particular, the direct conversion of human fibroblasts into induced neural progenitor cells (iNPCs) heralds the possibility of a novel autologous cell source for various applications such as cell replacement, disease modeling and drug screening. Here, we describe the isolation of adult human primary fibroblasts by skin biopsy and their efficient direct conversion into iNPCs by timely restricted expression of Oct4, Sox2, Klf4, as well as c-Myc. Sox2-positive neuroepithelial colonies appear after 17 days of induction and iNPC lines can be established efficiently by monoclonal isolation and expansion. Precise adjustment of viral multiplicity of infection and supplementation of leukemia inhibitory factor during the induction phase represent critical factors to achieve conversion efficiencies of up to 0.2%. Thus far, patient-specific iNPC lines could be expanded for more than 12 passages and uniformly display morphological and molecular features of neural stem/progenitor cells, such as the expression of Nestin and Sox2. The iNPC lines can be differentiated into neurons and astrocytes as judged by staining against TUJ1 and GFAP, respectively. In conclusion, we report a robust protocol for the derivation and direct conversion of human fibroblasts into stably expandable neural progenitor cells that might provide a cellular source for biomedical applications such as autologous neural cell replacement and disease modeling. PMID- 26275017 TI - 3D Organotypic Co-culture Model Supporting Medullary Thymic Epithelial Cell Proliferation, Differentiation and Promiscuous Gene Expression. AB - Intra-thymic T cell development requires an intricate three-dimensional meshwork composed of various stromal cells, i.e., non-T cells. Thymocytes traverse this scaffold in a highly coordinated temporal and spatial order while sequentially passing obligatory check points, i.e., T cell lineage commitment, followed by T cell receptor repertoire generation and selection prior to their export into the periphery. The two major resident cell types forming this scaffold are cortical (cTECs) and medullary thymic epithelial cells (mTECs). A key feature of mTECs is the so-called promiscuous expression of numerous tissue-restricted antigens. These tissue-restricted antigens are presented to immature thymocytes directly or indirectly by mTECs or thymic dendritic cells, respectively resulting in self tolerance. Suitable in vitro models emulating the developmental pathways and functions of cTECs and mTECs are currently lacking. This lack of adequate experimental models has for instance hampered the analysis of promiscuous gene expression, which is still poorly understood at the cellular and molecular level. We adapted a 3D organotypic co-culture model to culture ex vivo isolated mTECs. This model was originally devised to cultivate keratinocytes in such a way as to generate a skin equivalent in vitro. The 3D model preserved key functional features of mTEC biology: (i) proliferation and terminal differentiation of CD80(lo), Aire-negative into CD80(hi), Aire-positive mTECs, (ii) responsiveness to RANKL, and (iii) sustained expression of FoxN1, Aire and tissue-restricted genes in CD80(hi) mTECs. PMID- 26275018 TI - Crystal Habits of Itraconazole Microcrystals: Unusual Isomorphic Intergrowths Induced via Tuning Recrystallization Conditions. AB - The external appearance of a crystal of active pharmaceutical ingredient (API), usually referred to as a crystal habit, has a substantial impact on the API's physicochemical and physiochemical properties and, subsequently, its pharmaceutical performance. In this work, we investigate the role of different parameters of antisolvent crystallization impacting on the itraconazole (ITR) crystal habit and how this crystal habit manipulation, including crystal intergrowth, can affect crystal interactions with water molecules. Three distinct isomorphic crystal habits of ITR, a twinned blade-shaped (CHtw), a plate-shaped (CHpl), and a flat sheet-shaped with dendritic ends (CHsh), were obtained by controlling crystallization conditions. A liquid-liquid crystalline phase separation was observed as an intermediate stage preceding crystal growth. The March-Dollase parameter was used as a quantitative description of the preferred orientation, where CHsh exhibited the highest preferred orientation. The three crystal habits were evaluated for their wettability and water vapor distribution, at 37 degrees C, using the Young-Nelson fitting model. CHtw crystals sorbed a statistically significantly higher amount of water than CHpl and CHsh, which was attributed to the presence of crystal defects due to the twinning boundary. On the other hand, the amount of water adsorbed on the surface of CHpl and CHsh crystals was comparable and it was about twice that adsorbed on CHtw crystals. This was related to the abundance of hydrophilic chemical functionalities on the (010) facet of CHpl and CHsh as supported by the full interaction map carried out using Mercury software. This study expands investigations of the impact of crystal habit manipulation on API's functional properties beyond the well-known solubility improvement approaches. PMID- 26275019 TI - Selective Depletion of Microglia from Cerebellar Granule Cell Cultures Using L leucine Methyl Ester. AB - Microglia, the resident immunocompetent cells of the CNS, play multifaceted roles in modulating and controlling neuronal function, as well as mediating innate immunity. Primary rodent cell culture models have greatly advanced our understanding of neuronal-glial interactions, but only recently have methods to specifically eliminate microglia from mixed cultures been utilized. One such technique - described here - is the use of L-leucine methyl ester, a lysomotropic agent that is internalized by macrophages and microglia, wherein it causes lysosomal disruption and subsequent apoptosis(13,14). Experiments using L-leucine methyl ester have the power to identify the contribution of microglia to the surrounding cellular environment under diverse culture conditions. Using a protocol optimized in our laboratory, we describe how to eliminate microglia from P5 rodent cerebellar granule cell culture. This approach allows one to assess the relative impact of microglia on experimental data, as well as determine whether microglia are playing a neuroprotective or neurotoxic role in culture models of neurological conditions, such as stroke, Alzheimer's or Parkinson's disease. PMID- 26275020 TI - Tubular Structures Self-Assembled from a Bola-Amphiphilic Pillar[5]arene in Water and Applied as a Microreactor. AB - Various nanomorphologies were obtained by simply changing the fabrication conditions, such as the pH of the system, different solvent, or different concentration, of bola-amphiphilic pillar[5]arene Bola-AP5. Importantly, hybrid microtubules as a microreactor were successfully prepared by directly reducing AuCl4(-) on the surface of Bola-AP5-based tubular structures in water. PMID- 26275021 TI - Effects of aerobic exercise in early evening on the following nocturnal sleep and its haemodynamic response. AB - We determined effect of aerobic exercise in early evening on the quality, quantity, and haemodynamic response of subsequent nocturnal sleep in the home. Ten healthy young participants performed two protocols, with/without cycle ergometer exercise (60 min at 50% heart rate reserve) in early evening. Blood pressure (BP) (Holter) and physical activity (accelerometer) were measured from late afternoon of day 1 until noon of next day (day 2). Additionally, at bedtime participants were equipped with a small device worn on the wrist that identified sleep stage. There were no substantial differences in objective indices of sleep between two protocols (total sleep time: 438 +/- 76 vs. 457 +/- 64 min; P > 0.10). BP during nocturnal sleep tended to be lowered by prior exercise (MAP: 71 +/- 5 vs. 68 +/- 6 mmHg; P = 0.08). Aerobic exercise in early evening apparently has no acute effect on sleep per se, but seems to have a residual effect on haemodynamics, i.e. prolongation of post-exercise hypotension. PMID- 26275022 TI - Capture of Hyperthermal CO2 by Amorphous Water Ice via Molecular Embedding. AB - We present the first study detailing the capture and aggregation of hyperthermal CO2 molecules by amorphous solid water (ASW) under ultra-high vacuum conditions at 125 K, near the amorphous/crystalline transition. Using time-resolved in situ reflection-absorption infrared spectroscopy (RAIRS), CO2 molecules with translational energies above 3.0 eV are observed to directly embed underneath the vacuum-solid interface to become absorbed within the ice films despite an inability to adsorb at 125 K; this behavior is not observed for crystalline films. Upon embedding, the mobility of CO2 within 125 K amorphous ice and the strength of its intermolecular interactions result in its segregation into clusters within the ice films. Tracing the kinetics of CO2 embedding events under different energetic conditions allows for elucidation of the underlying dynamics, and we draw comparison with other projectiles we have studied to promote generalized conclusions in regard to empirical prediction of a projectile's embedding probability. Through application of a classical model of the entrance barrier for projectiles colliding with amorphous ice, we provide direct evidence for a unified connection between embedding probability and projectile momentum; an account of all embedding data measured by our group traces a unified barrier model. This work highlights the interplay between translational energy and momentum accommodation during collisions with ice in high speed gas flows. PMID- 26275023 TI - The influence of category representations on exemplar generation. AB - The present study examined the influence of category representations on exemplar generation, which has been neglected in previous category research. An experiment on college students manipulated the category representation of insects in three conditions (prototypes, exemplars, and the hybrid of prototypes and exemplars). Participants were asked to generate as many exemplars as possible. The results demonstrate that category representations affect and constrain exemplar generation. The new findings are as follows. In the prototype and hybrid conditions with the prototype representation, people tend to generate more valid exemplars by using the prototype mutation mechanism, and exemplar generation conforms to the family resemblance structure. Exemplar generation in the hybrid condition is additionally constrained by known exemplars. In the exemplar condition, people tend to generate fewer valid exemplars by using miscellaneous strategies, and their exemplar generation may not conform to the family resemblance structure. PMID- 26275024 TI - WITHDRAWN: Opioids for the management of breakthrough pain in cancer patients. PMID- 26275025 TI - Minimally invasive identification of degraded polyester-urethane magnetic tape using attenuated total reflection Fourier transform infrared spectroscopy and multivariate statistics. AB - Audio recordings are a significant component of the world's modern cultural history and are retained for future generations in libraries, archives, and museums. The vast majority of tapes contain polyester-urethane as the magnetic particle binder, the degradation of which threatens the playability and integrity of these often unique recordings. Magnetic tapes with stored historical data are degrading and need to be identified prior to digitization and/or preservation. We demonstrate the successful differentiation of playable and nonplayable quarter inch audio tapes, allowing the minimally invasive triage of tape collections. Without such a method, recordings are put at risk during playback, which is the current method for identifying degraded tapes. A total of 133 quarter-inch audio tapes were analyzed by attenuated total reflectance Fourier transform-infrared spectroscopy (ATR FT-IR). Classification of IR spectra in regards to tape playability was accomplished using principal component analysis (PCA) followed by quadratic discriminant analysis (QDA) and K-means cluster analysis. The first principal component suggests intensities at the following wavenumbers to be representative of nonplayable tapes: 1730 cm(-1), 1700 cm(-1), 1255 cm(-1), and 1140 cm(-1). QDA and cluster analysis both successfully identified 93.78% of nonplayable tapes in the calibration set and 92.31% of nonplayable tapes in the test set. This application of IR spectra assessed with multivariate statistical analysis offers a path to greatly improve efficiency of audio tape preservation. This rapid, minimally invasive technique shows potential to replace the manual playback test, a potentially destructive technique, ultimately allowing the safe preservation of culturally valuable content. PMID- 26275026 TI - Studying distributed cognition of simulation-based team training with DiCoT. AB - Health care organizations employ simulation-based team training (SBTT) to improve skill, communication and coordination in a broad range of critical care contexts. Quantitative approaches, such as team performance measurements, are predominantly used to measure SBTTs effectiveness. However, a practical evaluation method that examines how this approach supports cognition and teamwork is missing. We have applied Distributed Cognition for Teamwork (DiCoT), a method for analysing cognition and collaboration aspects of work settings, with the purpose of assessing the methodology's usefulness for evaluating SBTTs. In a case study, we observed and analysed four Emergo Train System(r) simulation exercises where medical professionals trained emergency response routines. The study suggests that DiCoT is an applicable and learnable tool for determining key distributed cognition attributes of SBTTs that are of importance for the simulation validity of training environments. Moreover, we discuss and exemplify how DiCoT supports design of SBTTs with a focus on transfer and validity characteristics. Practitioner Summary: In this study, we have evaluated a method to assess simulation-based team training environments from a cognitive ergonomics perspective. Using a case study, we analysed Distributed Cognition for Teamwork (DiCoT) by applying it to the Emergo Train System(r). We conclude that DiCoT is useful for SBTT evaluation and simulator (re)design. PMID- 26275027 TI - An All-Metal Aromatic Sandwich Complex [Sb3Au3Sb3](3-). AB - A sandwich complex, as exemplified by ferrocene in the 1950s, usually refers to one metal center bound by two arene ligands. The subject has subsequently been extended to carbon-free aromatic ligands and multiple-metal-atom "monolayered" center, but not to an all-metal species. Here, we describe the synthesis of an unprecedented all-metal aromatic sandwich complex, [Sb3Au3Sb3](3-), which was isolated as K([2.2.2]crypt)(+) salt and identified by single-crystal X-ray diffraction. Quantum chemical calculations indicate that intramolecular electron transfers for the three metallic layers (Sb -> Au donation and Sb <- Au back donation) markedly redistribute the valence electrons from the cyclo-Sb3 ligands and Au3 interlayer to the Au-Sb bonds, which hold the complex together via sigma bonding. Each cyclo-Sb3 possesses aromaticity with delocalized three-center three electron (3c-3e) pi bonds, which are essentially equivalent to a 3c-4e pipi* triplet system, following the reversed 4n Huckel rule for aromaticity in a triplet state. PMID- 26275028 TI - Targeting Drug Resistance in EGFR with Covalent Inhibitors: A Structure-Based Design Approach. AB - Receptor tyrosine kinases represent one of the prime targets in cancer therapy, as the dysregulation of these elementary transducers of extracellular signals, like the epidermal growth factor receptor (EGFR), contributes to the onset of cancer, such as non-small cell lung cancer (NSCLC). Strong efforts were directed to the development of irreversible inhibitors and led to compound CO-1686, which takes advantage of increased residence time at EGFR by alkylating Cys797 and thereby preventing toxic effects. Here, we present a structure-based approach, rationalized by subsequent computational analysis of conformational ligand ensembles in solution, to design novel and irreversible EGFR inhibitors based on a screening hit that was identified in a phenotype screen of 80 NSCLC cell lines against approximately 1500 compounds. Using protein X-ray crystallography, we deciphered the binding mode in engineered cSrc (T338M/S345C), a validated model system for EGFR-T790M, which constituted the basis for further rational design approaches. Chemical synthesis led to further compound collections that revealed increased biochemical potency and, in part, selectivity toward mutated (L858R and L858R/T790M) vs nonmutated EGFR. Further cell-based and kinetic studies were performed to substantiate our initial findings. Utilizing proteolytic digestion and nano-LC-MS/MS analysis, we confirmed the alkylation of Cys797. PMID- 26275029 TI - Assessment of fracture risk in patients with axial spondyloarthritis: a case control study using the fifth Korean National Health and Nutrition Examination Survey (KNHANES V). AB - OBJECTIVES: Axial spondyloarthritis (axSpA) is associated with low bone mineral density (BMD) and fractures, although the true fracture risk is unknown. The present study examined BMD and estimated the 10-year fracture risk in axSpA patients and matched controls and identified factors associated with a high fracture risk. METHOD: In total, 240 axSpA patients and 1200 healthy controls from the fifth Korean National Health and Nutrition Examination Survey (KNHANES V), matched using propensity scores, were included. Dual-energy X-ray absorptiometry (DXA) was used to measure lumbar spine and right femur BMD. Ten year risks of major osteoporotic and hip fractures were calculated using the Fracture Risk Assessment Tool (FRAX) in subjects aged >= 40 years. Multivariate linear regression models were used to explore factors associated with the 10-year fracture risk in axSpA patients. RESULTS: Hip and lumbar spine BMDs were lower in axSpA patients than in matched controls. Osteoporosis was present in 17% of axSpA patients and 3% of controls (p < 0.001). Low BMD was present in 22% of axSpA patients and 4% of controls aged < 50 years (p < 0.001). Ten-year major osteoporotic and hip fracture risks were significantly higher among axSpA patients. High 10-year fracture risk was observed in 10% of axSpA patients and 1.7% of controls (p = 0.003). The severity of sacroiliitis was independently associated with both major osteoporotic and hip fracture risks (p = 0.006 and 0.026, respectively). CONCLUSIONS: Patients with axSpA presented more frequently with low BMD and a higher calculated 10-year fracture risk than matched individuals. The severity of sacroiliitis was independently associated with a high 10-year fracture risk in axSpA patients. PMID- 26275030 TI - Synthesis of a novel superdisintegrant by starch derivatization with polysuccinimide and its application for the development of Ondansetron fast dissolving tablet. AB - CONTEXT: Disintegrants are the key excipients administered in tablet formulations to boost the decomposition of the tablet into smaller pieces in the gastrointestinal environment, thereby increasing the available surface area and enhancing a more rapid release of the active ingredient. OBJECTIVE: Polysuccinimide (PSI), a biodegradable polymer synthesized from aspartic acid, was reacted with starch and fully assessed by CHN, 1H-NMR, and FTIR. METHODS: PSI grafted starch (PSI-St) was synthesized and applied as a disintegrant in the formulation of a rapidly disintegrating tablet of Ondansetron, a nausea and vomiting medicine. The tablet formulated with the newly developed superdisintegrant was evaluated for hardness, friability, disintegration time, and dissolution rate, and the results were compared with tablets formulated with an identical composition of test formulation differing only in type of disintegrant. RESULTS: Tablets prepared with starch and tablets prepared with sodium starch glycolate (SSG) were used as negative and positive controls, respectively. Dissolution study results indicated that although the onset of disintegration action was faster for SSG than PSI-St, higher amounts of drug were released from tablets formulated from PSI-St than from those formulated from SSG during 10 min. CONCLUSION: It was concluded that the novel synthesized superdisintegrant has an appropriate potential for the application in the formulation of fast dissolving tablets. PMID- 26275031 TI - Close Surveillance with Long-Term Follow-up of Subjects with Preinvasive Endobronchial Lesions. AB - RATIONALE: Autofluorescence bronchoscopy (AFB) and computed tomography (CT) enable lung cancer (LC) detection at the early (pre-)invasive stage. However, LC risk in patients with preinvasive endobronchial lesions is unclear. OBJECTIVES: To assess LC incidence and identify potential risk determinants in patients with preinvasive lesions. METHODS: In our tertiary care referral center, 164 subjects with preinvasive lesions were monitored up to 12.5 years by repeated AFB and CT. Occurrence of LC was monitored. Clinical management depended on histological grade, with cancer patients receiving standard care. Potential risk determinants (smoking status, baseline histology, cancer history, and chronic obstructive pulmonary disease [COPD] status) were evaluated in relation to cancer occurrence, event-free survival (EFS), and overall survival (OS). MEASUREMENTS AND MAIN RESULTS: During surveillance (median of 30 mo, range 4-152) of 164 subjects with preinvasive lesions (80 high grade and 84 low grade at inclusion), 61 LCs were detected in 55 subjects (median time to event 16.5 mo). Twenty-three LCs (38%) were detected by CT, and 38 (62%) were detected by AFB. More cancers (36 of 61; 59%) developed from separate, rather than initial lesional sites. Subjects with high-grade lesions were more likely to be diagnosed with LC at the same or another site in the lungs than those with low-grade lesions (P = 0.03). Independent risk determinants for OS were previous curatively treated cancer and COPD (P <= 0.05). CONCLUSIONS: Presence of preinvasive lesions, especially high grade lesions, may serve as LC risk markers. LCs occur both at preinvasive lesion sites and elsewhere in the bronchial epithelium or lung parenchyma. Prospective validation of biomarkers and randomized intervention studies are needed to determine optimal management strategies. PMID- 26275032 TI - Treatment of axillary osmidrosis: a comparison between subcutaneous laser and superficial liposuction curettage. AB - BACKGROUND: Axillary osmidrosis can lead to personal and social problems, particularly in Asian culture. Superficial liposuction with curettage and subcutaneous laser are surgical intervention commonly used for osmidrosis. OBJECTIVE: Retrospectively, we compared the effectiveness and complications between superficial liposuction with curettage and subcutaneous laser in an Asian population. METHODS: Totally, 66 and 19 patients receiving subcutaneous laser and superficial liposuction with curettage (LC) were recruited. The effectiveness of treatment was assessed by patients subjectively. Recurrence rate of osmidrosis and complications were also evaluated. RESULTS: 95% of patients showed good-to excellent improvement in LC group and only 30% of patients showing good-to excellent results in laser group (P < 0.01). Binary logistic regression revealed that the odds ratio of LC was 53.288 (P = 0.006) for >50% improvement in osmidrosis. The recurrence rate was not significantly different (P = 0.139), however, the duration to recurrence of osmidrosis was significantly longer in LC group (P < 0.01). The complication rate was 31% in LC group and 6% in laser group (P < 0.01). CONCLUSION: Superficial liposuction with curettage provides more effective treatment with higher complication rates and is possibly suitable for severe patients. For mild-to-moderate osmidrosis, or preferring a better cosmetic result or short recovery, subcutaneous laser could be applied. PMID- 26275033 TI - Using the M13 Phage as a Biotemplate to Create Mesoporous Structures Decorated with Gold and Platinum Nanoparticles. AB - By taking advantage of the physical and chemical properties of the M13 bacteriophage, we have used this virus to synthesize mesoporous silica structures. Major coat protein p8 was chemically modified by attaching thiol groups. As we show, the resulting thiolated phage can be used as a biotemplate able to direct the formation of mesoporous silica materials. Simultaneously, this thiol functionality acts as an anchor for binding metal ions, such as Au(3+) and Pt(4+), forming reactive M13-metal ionic complexes which evolve into metal nanoparticles (NPs) trapped in the mesoporous network. Interestingly, Au(3+) ions are reduced to Au(0) NPs by the protein residues without requiring an external reducing agent. Likewise, silica mesostructures decorated with Au and Pt NPs are prepared in a one-pot synthesis and characterized using different techniques. The obtained results allow us to propose a mechanism of formation. In addition, gold containing mesoporous structures are tested for the reduction of 4-nitrophenol (4 NP) and methylene blue (MB) in the presence of NaBH4. Although all of the gold containing catalysts exhibit catalytic activity, those obtained with thiolated phages present a better performance than that obtained with M13 alone. This behavior is ascribed to the position of the Au NPs, which are partially embedded in the wall of the final mesostructures. PMID- 26275034 TI - Maternal Floor Infarction/Massive Perivillous Fibrin Deposition Associated with Hypercoiling of a Single-Artery Umbilical Cord: A Case Report. AB - Maternal floor infarction is a rare and idiopathic placental disorder associated with adverse obstetric outcomes and a high rate of recurrence in subsequent pregnancies. The pathogenesis of maternal floor infarction is unclear but has been linked to diverse underlying maternal conditions, including gestational hypertension/preeclampsia, immune-mediated diseases, and thrombophilia. Few reports link maternal floor infarction to fetoplacental conditions. We report a 34-week, macerated, growth-restricted male fetus for which the placenta showed maternal floor infarction. The umbilical cord showed excessive coiling and a single umbilical artery. These cord changes are postulated to have resulted in increased placental villous resistance and decreased fetal blood flow, creating a hydrostatic pressure gradient between the villous stroma and the intervillous space. The pressure changes could then lead to trophoblast damage and fibrinoid deposition, contributing to the maternal floor infarction in this case. PMID- 26275035 TI - High prevalence of unwanted pregnancies and induced abortions among HIV-infected women from Western India: need to emphasize dual method use? AB - This study examines the prevalence, reasons, and predictors of unwanted pregnancies and induced abortions among ever married HIV-infected women attending a care facility in Maharashtra, Western India, and discusses its programmatic and policy implications. Retrospectively collected data of pregnancies conceived after the diagnosis of HIV were analyzed using descriptive and logistic regression techniques. Among the 622 women interviewed, 113 women had 158 pregnancies with known outcomes after HIV diagnosis. Among these pregnancies, 80 (51%) were unwanted and 79 (50%) were voluntarily terminated. Fear of transmitting HIV to the child was a frequently mentioned reason for an unwanted pregnancy (71.8%) and induced abortion (59.5%). Women from urban areas [OR 2.43 (95% CI 1.23-4.79)] and with two or more live births before HIV diagnosis [OR 3.33 (95% CI 1.36-8.20)] were significantly more likely to report an unwanted pregnancy. Women with two or more live births before HIV diagnosis [OR 3.16 (95% CI 1.20-8.35)], who did not know that HIV transmission to the baby can be prevented [OR 3.29 (95% CI 1.48-7.34)] and with an unwanted pregnancy [OR 4.82 (95% CI 2.33-10.00)], were significantly more likely to terminate the pregnancy. Despite increased coverage of antiretroviral treatment, effective provision of reproductive healthcare services to HIV-infected women remains challenging. A high prevalence of unwanted pregnancies and induced abortions and a low level of knowledge about prevention of mother to child transmission (PMTCT) underscore the need for preconception counseling and provision of comprehensive family planning services to HIV-infected women. Enrolling all HIV-infected pregnant women, irrespective of their decision to continue with their pregnancy, in the PMTCT program and discussing with HIV-infected women and their partners at HIV diagnosis a full array of contraceptive methods and not just consistent use of condoms might be helpful in reducing unwanted pregnancies. PMID- 26275036 TI - Substance Use, Bullying, and Body Image Disturbances in Adolescents and Young Adults Under the Prism of a 3D Simulation Program: Validation of MySchool4web. AB - BACKGROUND: The use of virtual reality or three-dimensional (3D) simulation programs has been explored in different mental health problems and contexts. One of the applications that showed evidence of a suitable assessment for behavioral and emotional problems in adolescents is the 3D questionnaire called MySchool4web. The aim of this work was to analyze the psychometric properties of a tailored version of MySchool4web. MATERIALS AND METHODS: A correlational, nonexperimental, cross-sectional study was carried out. The participants were 668 secondary students from schools in Santiago, Chile with a mean age of 15.74 years. Adolescents completed MySchool4web in the informatics classroom of each school. RESULTS: Results indicated that two of the items had to be removed, and a three-factor solution was found representing the dimensions substance use, bullying, and body image. This final model of 10 items showed acceptable internal consistency per factor, and its scores were significantly associated with other related measures in nine items. CONCLUSIONS: These outcomes suggest that this version of MySchool4web is a reliable and valid measure of a 3D instrument for the screening of risky behaviors and emotional problems in adolescents and young adults in a school context. PMID- 26275037 TI - Purinergic signaling in the ovary. AB - Adenosine triphosphate (ATP) is released from the cell by multiple mechanisms. The extracellular form of this purine is processed by ectonucleotidases, resulting in a variety of dephosphorylated metabolites that can bind to specific receptors found in the membrane of target cells; such purinergic signaling is important as an autocrine-paracrine intercellular communication system that influences tissue physiology. In this review, we summarize the studies analyzing purinergic activity in the ovary, which can modulate cellular physiology including sensitivity to gonadotropins-in several ovarian cell types, including the cumulus-cell complex, granulosa cells, theca cells, and the ovarian surface epithelium. These functions support a role for ATP as an important intra-ovarian messenger, and open new lines of research that can improve our understanding of mechanisms regulating ovarian function and the fine-tuning of folliculogenesis. PMID- 26275038 TI - Isolation and characterization of a new bioactive isoflavone from Derris eriocarpa. AB - Derris eriocarpa How is an important medicinal plant, which is used as Zhuang ethnomedicine and Dai ethnomedicine to treat various diseases. One new compound, 3',4'-di-O-methylene-5-hydroxy-7-methoxy-6-isopentenyl isoflavone (1) and a known synthetic but new naturally occurring compound trans-3,4,5-trimethoxy-4' isopentenyloxyl-stilbene (2), together with five known compounds, 5,7-dimethoxy-6 (3-methyl-2-butenyl)-4'-hydroxyl isoflavones (3), robustone (4), trans-3,4,5,4' tetramethoxy-stilbene (5), robustic acid (6), and robustin (7) were isolated from the stem of D. eriocarpa. Spectroscopic analysis revealed the chemical structures of compounds 1-7.. Compounds 1 and 3 exhibited significant scavenging activities against 1,1-diphenyl-2-picrylhydrazyl radical and superoxide anions. Compounds 1 3 exhibited potent antiproliferative activity on Hela cells. PMID- 26275039 TI - Effects of Fentanyl on Emergence Agitation in Children under Sevoflurane Anesthesia: Meta-Analysis of Randomized Controlled Trials. AB - BACKGROUND AND OBJECTIVES: The goal of this meta-analysis study was to assess the effects of fentanyl on emergence agitation (EA) under sevoflurane anesthesia in children. SUBJECTS AND METHODS: We searched electronic databases (PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials) for articles published until December 2014. Randomized controlled trials (RCTs) that assessed the effects of fentanyl and placebo on EA under sevoflurane anesthesia in children that the outcome were the incidence of EA, postoperative pain, emergence time or adverse effects were included in this meta-analysis. RESULTS: A total of 16 studies, including 1362 patients (737 patients for the fentanyl group and 625 for the placebo group), were evaluated in final analysis. We found that administration of fentanyl decreased the incidences of EA (RR = 0.37, 95% CI 0.27~0.49, P<0.00001) and postoperative pain (RR = 0.59, 95% CI 0.41~0.85, P = 0.004) but increased the incidence of postoperative nausea and vomiting (PONV) (RR = 2.23, 95% CI 1.33~3.77, P = 0.003). The extubation time (WMD = 0.71 min, 95% CI 0.12~1.3, P = 0.02), emergence time (WMD = 4.90 min, 95% CI 2.49~7.30, P<0.0001), and time in the postanesthesia care unit (PACU) (WMD = 2.65 min, 95% CI 0.76~4.53, P = 0.006) were slightly increased. There were no significant differences in the time to discharge of day patients (WMD = 3.72 min, 95% CI 2.80~10.24, P = 0.26). CONCLUSION: Our meta-analysis suggests that fentanyl decreases the incidence of EA under sevoflurane anesthesia in children and postoperative pain, but has a higher incidence of PONV. Considering the inherent limitations of the included studies, more RCTs with extensive follow-up should be performed to validate our findings in the future. PMID- 26275040 TI - Parameter Interpretation and Reduction for a Unified Statistical Mechanical Surface Tension Model. AB - Surface properties of aqueous solutions are important for environments as diverse as atmospheric aerosols and biocellular membranes. Previously, we developed a surface tension model for both electrolyte and nonelectrolyte aqueous solutions across the entire solute concentration range (Wexler and Dutcher, J. Phys. Chem. Lett. 2013, 4, 1723-1726). The model differentiated between adsorption of solute molecules in the bulk and surface of solution using the statistical mechanics of multilayer sorption solution model of Dutcher et al. (J. Phys. Chem. A 2013, 117, 3198-3213). The parameters in the model had physicochemical interpretations, but remained largely empirical. In the current work, these parameters are related to solute molecular properties in aqueous solutions. For nonelectrolytes, sorption tendencies suggest a strong relation with molecular size and functional group spacing. For electrolytes, surface adsorption of ions follows ion surface-bulk partitioning calculations by Pegram and Record (J. Phys. Chem. B 2007, 111, 5411 5417). PMID- 26275041 TI - Discovering Hidden Diversity of Characins (Teleostei: Characiformes) in Ecuador's Yasuni National Park. AB - BACKGROUND: Management and conservation of biodiversity requires adequate species inventories. The Yasuni National Park is one of the most diverse regions on Earth and recent studies of terrestrial vertebrates, based on genetic evidence, have shown high levels of cryptic and undescribed diversity. Few genetic studies have been carried out in freshwater fishes from western Amazonia. Thus, in contrast with terrestrial vertebrates, their content of cryptic diversity remains unknown. In this study, we carried out genetic and morphological analyses on characin fishes at Yasuni National Park, in eastern Ecuador. Our goal was to identify cryptic diversity among one of the most speciose fish families in the Amazon region. This is the first time that genetic evidence has been used to assess the species content of the Napo Basin, one of the richest regions in vertebrate diversity. RESULTS: Phylogenetic analyses of partial mitochondrial 16S ribosomal RNA gene (~600 pb) DNA sequences from 232 specimens of the family Characidae and its closest groups revealed eight candidate new species among 33 species sampled, representing a 24% increase in species number. Analyses of external morphology allowed us to confirm the species status of six of the candidate species. CONCLUSIONS: Our results show high levels of cryptic diversity in Amazonian characins. If this group is representative of other Amazonian fish, our results would imply that the species richness of the Amazonian ichthyofauna is highly underestimated. Molecular methods are a necessary tool to obtain more realistic inventories of Neotropical freshwater fishes. PMID- 26275043 TI - Trend of Narratives in the Age of Misinformation. AB - Social media enabled a direct path from producer to consumer of contents changing the way users get informed, debate, and shape their worldviews. Such a disintermediation might weaken consensus on social relevant issues in favor of rumors, mistrust, or conspiracy thinking-e.g., chem-trails inducing global warming, the link between vaccines and autism, or the New World Order conspiracy. Previous studies pointed out that consumers of conspiracy-like content are likely to aggregate in homophile clusters-i.e., echo-chambers. Along this path we study, by means of a thorough quantitative analysis, how different topics are consumed inside the conspiracy echo-chamber in the Italian Facebook. Through a semi automatic topic extraction strategy, we show that the most consumed contents semantically refer to four specific categories: environment, diet, health, and geopolitics. We find similar consumption patterns by comparing users activity (likes and comments) on posts belonging to these different semantic categories. Finally, we model users mobility across the distinct topics finding that the more a user is active, the more he is likely to span on all categories. Once inside a conspiracy narrative users tend to embrace the overall corpus. PMID- 26275042 TI - Tetramethylpyrazine (TMP), an Active Ingredient of Chinese Herb Medicine Chuanxiong, Attenuates the Degeneration of Trabecular Meshwork through SDF 1/CXCR4 Axis. AB - BACKGROUND: A traditional Chinese medicine, Tetramethylpyrazine (TMP), has been prescribed as a complementary treatment for glaucoma to improve patient prognosis. However, the pharmacological mechanism of action of TMP is poorly understood. In previous studies, we demonstrated that TMP exerts potent inhibitory effects on neovascularization, suppresses the tumorigenic behavior of glioma cells, and protects neural cells by regulating CXCR4 expression. Here, we further investigated whether the SDF-1/CXCR4 pathway is also involved in the TMP mediated activity in trabecular meshwork cells. METHODOLOGY/PRINCIPAL FINDINGS: CXCR4 expression was examined by quantitative real-time PCR in trabecular and iris specimens from 54 primary open-angle glaucoma (POAG) patients who required surgery and 19 non-glaucomatous donors. Our data revealed markedly elevated CXCR4 expression in the trabecular meshwork of POAG patients compared with that of controls. Consistently, CXCR4 expression was much higher in glaucomatous trabecular meshwork cells than in normal trabecular meshwork cells. Using RT-PCR and western blot assays, we determined that glaucoma-related cytokines and dexamethasone (DEX) also significantly up-regulated CXCR4 expression in primary human trabecular meshwork (PHTM) cells. Moreover, the TGF-beta1-mediated induction of CXCR4 expression in PHTM cells was markedly down-regulated by TMP compared with control treatment (PBS) and the CXCR4 antagonist AMD3100. In addition, TMP could counteract the TGF-beta1-induced effects on stress fiber accumulation and expansion of PHTM cells. TMP markedly suppressed the migration of PHTM cells stimulated by TGF-beta1 in transwell and scratch wound assays. TMP also suppressed the extracellular matrix (ECM) accumulation induced by TGF-beta2. CONCLUSIONS: Our findings demonstrate that CXCR4 might be involved in the pathogenetic changes in the trabecular meshwork of patients with POAG. Additionally, TMP might exert its beneficial effects in POAG patients by down regulating CXCR4 expression. PMID- 26275044 TI - Kinetic Analysis of Haloacetonitrile Stability in Drinking Waters. AB - Haloacetonitriles (HANs) are an important class of drinking water disinfection byproducts (DBPs) that are reactive and can undergo considerable transformation on time scales relevant to system distribution (i.e., from a few hours to a week or more). The stability of seven mono-, di-, and trihaloacetonitriles was examined under a variety of conditions including different pH levels and disinfectant doses that are typical of drinking water distribution systems. Results indicated that hydroxide, hypochlorite, and their protonated forms could react with HANs via nucleophilic attack on the nitrile carbon, forming the corresponding haloacetamides (HAMs) and haloacetic acids (HAAs) as major reaction intermediates and end products. Other stable intermediate products, such as the N chloro-haloacetamides (N-chloro-HAMs), may form during the course of HAN chlorination. A scheme of pathways for the HAN reactions was proposed, and the rate constants for individual reactions were estimated. Under slightly basic conditions, hydroxide and hypochlorite are primary reactants and their associated second-order reaction rate constants were estimated to be 6 to 9 orders of magnitude higher than those of their protonated conjugates (i.e., neutral water and hypochlorous acid), which are much weaker but more predominant nucleophiles at neutral and acidic pHs. Developed using the estimated reaction rate constants, the linear free energy relationships (LFERs) summarized the nucleophilic nature of HAN reactions and demonstrated an activating effect of the electron withdrawing halogens on nitrile reactivity, leading to decreasing HAN stability with increasing degree of halogenation of the substituents, while subsequent shift from chlorine to bromine atoms has a contrary stabilizing effect on HANs. The chemical kinetic model together with the reaction rate constants that were determined in this work can be used for quantitative predictions of HAN concentrations depending on pH and free chlorine contact times (CTs), which can be applied as an informative tool by drinking water treatment and system management engineers to better control these emerging nitrogenous DBPs, and can also be significant in making regulatory decisions. PMID- 26275045 TI - Energy-Transfer Schemes To Probe Fluorescent Nanocarriers and Their Emissive Cargo. AB - A strategy to probe supramolecular nanocarriers and their cargo in the intracellular space was developed on the basis of fluorescence measurements and energy transfer. It relies on the covalent attachment of an energy donor, or acceptor, to the macromolecular backbone of amphiphilic polymers and the noncovalent encapsulation of a complementary acceptor, or donor, in the resulting micelles. In aqueous environments, these macromolecules self-assemble into nanostructured constructs and bring the complementary chromophores in close proximity to enable efficient energy transfer. These supramolecular assemblies travel from the extracellular to the intracellular space and retain their integrity in the process. Indeed, donors and acceptors remain close to each other after internalization, and excitation of the former chromophores translates into significant intracellular emission from the latter. Furthermore, these supramolecular assemblies exchange their components with fast kinetics in aqueous dispersions because of the reversible character of the noncovalent contacts holding them together. As a result, micelles incorporating exclusively the donors and nanocarriers containing only the acceptors scramble their chromophoric building blocks, upon mixing, to allow the transfer of energy. These dynamic processes can be reproduced in the intracellular environment with the sequential incubation of cells with the two sets of complementary nanostructured assemblies. Thus, these operating principles and choice of supramolecular synthons are particularly valuable to monitor self-assembling nanocarriers and their cargo inside living cells and can facilitate the elucidation of the behavior of these promising delivery vehicles in a diversity of biological specimens. PMID- 26275047 TI - A Safe and Simple Laparoscopic Cold Knife Section Technique for Bulky Uterus Removal. AB - BACKGROUND: Morcellation of a bulky uterus after total laparoscopic hysterectomy (TLH) is a challenge for those dealing with advanced laparoscopic surgery. However, there are no laparoscopic standardized procedures available to date. We developed a laparoscopic cold knife technique with the aim of demonstrating a simple and reproducible method of sectioning and vaginal retrieval of the bulky uterus. MATERIALS AND METHODS: From June 2012 to June 2014, patients who underwent TLH for benign indication, with a uterus size over 12 gestational weeks, were prospectively admitted into the clinical study. Before specimen vaginal retrieval, uterine section was achieved by Chardonnens' cold knife with the aim of obtaining two uterus halves sectioned longitudinally and held together only by the posterior cervical wall. We performed the procedure in a containment system to avoid myometrial spillage into the abdomen. RESULTS: Twenty-nine women with a bulky uterus were treated by TLH and the cold knife section technique. The uterine size ranged from 240 to 850 g (median, 460 g), and the average morcellation operative time was 11.3 minutes. All procedures were completed successfully without complications. CONCLUSIONS: Our data suggest that the cold knife uterine section technique after TLH is a feasible, simple, and reproducible method of bulky uterus morcellation, even if further research is advisable to fully evaluate the advantages of this procedure. PMID- 26275046 TI - Hepatitis B Virus Genotype D Isolates Circulating in Chapeco, Southern Brazil, Originate from Italy. AB - Hepatitis B virus genotype A1 (HBV/A1), of African origin, is the most prevalent genotype in Brazil, while HBV/F predominates in the other South American countries. However, HBV/D is the most common in the three states of southern Brazil, where 'islands' of elevated prevalence, as Chapeco and other cities, have been described. In this study, 202 HBV chronic carriers attending in 2013 the viral hepatitis ambulatory of Chapeco, were investigated. In comparison with previous studies performed in the same ambulatory, a rapid aging of the HBV infected population was observed (mean age of the newly diagnosed patients increasing from 29.9 +/- 10.3 years in 1996 to 44.4 +/- 13.3 years in 2013), probably due to a singular vaccination schedule at Chapeco that included not only children but also adolescents. Phylogenetic and BLAST analyses (S region) classified 91 HBV isolates into genotypes A (n = 3) and D (n = 88). The majority of HBV/D isolates were closely related to D3 sequences. To understand the reasons for the absence or near absence of genotypes A and F, and how HBV/D was introduced in the south of Brazil, HBV/D infected patients were inquired about their genealogical and geographical origins. Forty-three (52%) patients have their four grandparents of Italian origin, vs. seven (8%) who have their four grandparents of Brazilian origin. At all, 65 out of 83 (78%) patients had at least one grandparent originating from Italy. Taking into consideration the fact that Italy is one of the few countries where subgenotype D3 is predominant, the results strongly suggested that HBV/D was introduced in Brazil through Italian immigration which culminated between 1870 and 1920. PMID- 26275048 TI - Functional RelBE-Family Toxin-Antitoxin Pairs Affect Biofilm Maturation and Intestine Colonization in Vibrio cholerae. AB - Toxin-antitoxin (TA) systems are small genetic elements that typically encode a stable toxin and its labile antitoxin. These cognate pairs are abundant in prokaryotes and have been shown to regulate various cellular functions. Vibrio cholerae, a human pathogen that is the causative agent of cholera, harbors at least thirteen TA loci. While functional HigBA, ParDE have been shown to stabilize plasmids and Phd/Doc to mediate cell death in V. cholerae, the function of seven RelBE-family TA systems is not understood. In this study we investigated the function of the RelBE TA systems in V. cholerae physiology and found that six of the seven relBE loci encoded functional toxins in E. coli. Deletion analyses of each relBE locus indicate that RelBE systems are involved in biofilm formation and reactive oxygen species (ROS) resistance. Interestingly, all seven relBE loci are induced under the standard virulence induction conditions and two of the relBE mutants displayed a colonization defect, which was not due to an effect on virulence gene expression. Although further studies are needed to characterize the mechanism of action, our study reveals that RelBE systems are important for V. cholerae physiology. PMID- 26275050 TI - The motor inhibition system in Parkinson's disease with levodopa-induced dyskinesias. AB - BACKGROUND: Parkinson's disease is primarily a disorder of response initiation characterized by an excessive motor inhibition, whereas levodopa-induced dyskinesias are clearly a clinical expression of disinhibition of movements. OBJECTIVE: That levodopa-induced dyskinesias are linked to dysfunctions of inhibitory brain network has recently been proposed, but no investigation of behavioral performance during action inhibition task in these patients has been published. METHODS: Twenty-four Parkinson's disease patients with or without levodopa-induced dyskinesias tested on or off their medications underwent functional magnetic resonance imaging investigation during the execution of a stop-signal inhibition task. In particular, we were interested in evaluating the neural correlates of stop-related conditions: StopInhibit task (in which patients had to successfully inhibit their responses) and StopRespond task (Stop trials with erroneous button press). Both tasks were compared against Go trials. RESULTS: Levodopa intake in dyskinetic patients tended to worsen inhibitory control during the StopInhibit task, while significantly affecting the ability to monitor motor responses when patients failed to stop (StopRespond task). Functional analysis showed that, during the StopInhibit task, dyskinetic patients were characterized by decreased activity of the right inferior frontal cortex after levodopa intake, whereas patients without dyskinesias showed a reverse effect. A similar group * levodopa interaction effect was detected in the medial frontal cortex during the execution of the StopRespond task, in which dyskinetic patients showed increased activity after dopaminergic therapy CONCLUSIONS: Our study demonstrated that levodopa intake in dyskinetic patients tends to alter the functioning of some parts of the neural network involved in motor inhibition. PMID- 26275049 TI - Reconstructing Colonization Dynamics of the Human Parasite Schistosoma mansoni following Anthropogenic Environmental Changes in Northwest Senegal. AB - BACKGROUND: Anthropogenic environmental changes may lead to ecosystem destabilization and the unintentional colonization of new habitats by parasite populations. A remarkable example is the outbreak of intestinal schistosomiasis in Northwest Senegal following the construction of two dams in the '80s. While many studies have investigated the epidemiological, immunological and geographical patterns of Schistosoma mansoni infections in this region, little is known about its colonization history. METHODOLOGY/PRINCIPAL FINDINGS: Parasites were collected at several time points after the disease outbreak and genotyped using a 420 bp fragment of the mitochondrial cytochrome c oxidase subunit 1 gene (cox1) and nine nuclear DNA microsatellite markers. Phylogeographic and population genetic analyses revealed the presence of (i) many genetically different haplotypes at the non-recombining mitochondrial marker and (ii) one homogenous S. mansoni genetic group at the recombining microsatellite markers. These results suggest that the S. mansoni population in Northwest Senegal was triggered by intraspecific hybridization (i.e. admixture) between parasites that were introduced from different regions. This would comply with the extensive immigration of infected seasonal agricultural workers from neighboring regions in Senegal, Mauritania and Mali. The spatial and temporal stability of the established S. mansoni population suggests a swift local adaptation of the parasite to the local intermediate snail host Biomphalaria pfeifferi at the onset of the epidemic. CONCLUSIONS/SIGNIFICANCE: Our results show that S. mansoni parasites are very successful in colonizing new areas without significant loss of genetic diversity. Maintaining high levels of diversity guarantees the adaptive potential of these parasites to cope with selective pressures such as drug treatment, which might complicate efforts to control the disease. PMID- 26275052 TI - Negative experiences and predonation blood pressure at the subsequent donation in blood donors. AB - BACKGROUND: Negative donation experiences, like being deferred or experiencing an adverse reaction, might upset blood donors, resulting in anticipatory stress responses such as elevated blood pressure at the subsequent visit. We therefore explored associations between blood donors' negative donation experiences and their blood pressure at the subsequent visit. STUDY DESIGN AND METHODS: Blood pressure of donors with no history of negative experiences in three consecutive donations was compared to the blood pressure of donors with a negative experience during the second of the three donations. Blood pressure (systolic and diastolic) measured prior to the third donation was compared between the two groups, using linear regression analyses. Two types of negative experiences (adverse reactions and deferral) were analysed, stratifying for donation type and sex, and adjusting for age and predonation blood pressure at baseline. RESULTS: In total, 248 118 (50% female) donors were included in the analyses. Eleven per cent (26 380 donors, 61% female) had experienced a negative experience. Fainting and dizziness were associated with significant (P < 0.05) increases in systolic blood pressure: in men, 3.0 mmHg (fainting) and 2.0 mmHg (dizziness); in women, 2.0 mmHg (fainting) and 1.4 mmHg (dizziness). Deferral was associated with significant (P < 0.05) increases in both systolic (men: 0.7 mmHg, women: 0.3 mmHg) and diastolic (men: 0.2 mmHg, women: 0.3 mmHg) blood pressure. CONCLUSION: Whole blood donations with negative experiences were associated with a statistically significant higher predonation blood pressure at the subsequent visit. This indicates that negative experiences might cause an anticipatory stress reaction in a subsequent donation. PMID- 26275051 TI - Microarray and Proteomic Analyses of Myeloproliferative Neoplasms with a Highlight on the mTOR Signaling Pathway. AB - The gene and protein expression profiles in myeloproliferative neoplasms (MPNs) may reveal gene and protein markers of a potential clinical relevance in diagnosis, treatment and prediction of response to therapy. Using cDNA microarray analysis of 25,100 unique genes, we studied the gene expression profile of CD34+ cells and granulocytes obtained from peripheral blood of subjects with essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). The microarray analyses of the CD34+ cells and granulocytes were performed from 20 de novo MPN subjects: JAK2 positive ET, PV, PMF subjects, and JAK2 negative ET/PMF subjects. The granulocytes for proteomic studies were pooled in 4 groups: PV with JAK2 mutant allele burden above 80%, ET with JAK2 mutation, PMF with JAK2 mutation and ET/PMF with no JAK2 mutation. The number of differentially regulated genes was about two fold larger in CD34+ cells compared to granulocytes. Thirty six genes (including RUNX1, TNFRSF19) were persistently highly expressed, while 42 genes (including FOXD4, PDE4A) were underexpressed both in CD34+ cells and granulocytes. Using proteomic studies, significant up-regulation was observed for MAPK and PI3K/AKT signaling regulators that control myeloid cell apoptosis and proliferation: RAC2, MNDA, S100A8/9, CORO1A, and GNAI2. When the status of the mTOR signaling pathway related genes was analyzed, PI3K/AKT regulators were preferentially up-regulated in CD34+ cells of MPNs, with down-regulated major components of the protein complex EIF4F. Molecular profiling of CD34+ cells and granulocytes of MPN determined gene expression patterns beyond their recognized function in disease pathogenesis that included dominant up-regulation of PI3K/AKT signaling. PMID- 26275054 TI - Correction: Aerobic Capacity, Physical Activity and Metabolic Risk Factors in Firefighters Compared with Police Officers and Sedentary Clerks. PMID- 26275053 TI - Runx1 Transcription Factor Is Required for Myoblasts Proliferation during Muscle Regeneration. AB - Following myonecrosis, muscle satellite cells proliferate, differentiate and fuse, creating new myofibers. The Runx1 transcription factor is not expressed in naive developing muscle or in adult muscle tissue. However, it is highly expressed in muscles exposed to myopathic damage yet, the role of Runx1 in muscle regeneration is completely unknown. Our study of Runx1 function in the muscle's response to myonecrosis reveals that this transcription factor is activated and cooperates with the MyoD and AP-1/c-Jun transcription factors to drive the transcription program of muscle regeneration. Mice lacking dystrophin and muscle Runx1 (mdx-/Runx1f/f), exhibit impaired muscle regeneration leading to age dependent muscle waste, gradual decrease in motor capabilities and a shortened lifespan. Runx1-deficient primary myoblasts are arrested at cell cycle G1 and consequently differentiate. Such premature differentiation disrupts the myoblasts' normal proliferation/differentiation balance, reduces the number and size of regenerating myofibers and impairs muscle regeneration. Our combined Runx1-dependent gene expression, ChIP-seq, ATAC-seq and histone H3K4me1/H3K27ac modification analyses revealed a subset of Runx1-regulated genes that are co occupied by MyoD and c-Jun in mdx-/Runx1f/f muscle. The data provide unique insights into the transcriptional program driving muscle regeneration and implicate Runx1 as an important participant in the pathology of muscle wasting diseases. PMID- 26275055 TI - Living within stories: Exploring the experiences of people with transient ischemic attack. AB - A transient ischemic attack (TIA) significantly increases a person's risk of ischemic stroke. However, little is known about the experiences of these people or what influences their decision to access care. This article explores the stories of three people who experienced a TIA. All participants were interviewed after receiving a diagnosis of TIA by a specialist neurologist. By utilizing a framework of narrative inquiry, several storylines were revealed across temporal, social, and geographical landscapes. The main storylines include: bodily disruption, time stasis, altered temporal perceptions, the roles of others, and help-seeking behavior. The primary author also reflects upon his own origin and explores how this inquiry has influenced his perceptions, career, and nursing practice. This inquiry may assist healthcare workers to gain insight into the experiences of people with TIA and suggests how involvement of significant others is beneficial when educating people at risk of TIA. PMID- 26275056 TI - Molecular and Phenotypic Characterization of Staphylococcus epidermidis Isolates from Healthy Conjunctiva and a Comparative Analysis with Isolates from Ocular Infection. AB - Staphylococcus epidermidis is a common commensal of healthy conjunctiva and it can cause endophthalmitis, however its presence in conjunctivitis, keratitis and blepharitis is unknown. Molecular genotyping of S. epidermidis from healthy conjunctiva could provide information about the origin of the strains that infect the eye. In this paper two collections of S. epidermidis were used: one from ocular infection (n = 62), and another from healthy conjunctiva (n = 45). All isolates were genotyped by pulsed field gel electrophoresis (PFGE), multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec), detection of the genes icaA, icaD, IS256 and polymorphism type of agr locus. The phenotypic data included biofilm production and antibiotic resistance. The results displayed 61 PFGE types from 107 isolates and they were highly discriminatory. MLST analysis generated a total of 25 STs, of which 11 STs were distributed among the ocular infection isolates and lineage ST2 was the most frequent (48.4%), while 14 STs were present in the healthy conjunctiva isolates and lineage ST5 was the most abundant (24.4%). By means of a principal coordinates analysis (PCoA) and a discriminant analysis (DA) it was found that ocular infection isolates had as discriminant markers agr III or agr II, SCCmec V or SCCmec I, mecA gene, resistance to tobramycin, positive biofilm, and IS256+. In contrast to the healthy conjunctiva isolates, the discriminating markers were agr I, and resistance to chloramphenicol, ciprofloxacin, gatifloxacin and oxacillin. The discriminant biomarkers of ocular infection were examined in healthy conjunctiva isolates, and it was found that 3 healthy conjunctiva isolates [two with ST2 and another with ST9] (3/45, 6.66%) had similar genotypic and phenotypic characteristics to ocular infection isolates, therefore a small population from healthy conjunctiva could cause an ocular infection. These data suggest that the healthy conjunctiva isolates do not, in almost all cases, infect the eye due to their large genotypic and phenotypic difference with the ocular infection isolates. PMID- 26275057 TI - Household Storage of Medicines and Associated Factors in Tigray Region, Northern Ethiopia. AB - INTRODUCTION: The presence of medicines in households is a risk factor for irrational drug use. This study aimed at investigating the prevalence and factors associated with home storage of medicines in Tigray Region, Ethiopia. METHOD: A community based cross-sectional study was conducted in April 2013 in Tigray Region, Ethiopia. A total of 1034 participants were enrolled in the study. A multi-stage sampling method was employed to select households. Data were collected with the help of a pre-tested structured questionnaire and analyzed using descriptive statistics and bivariate and multivariate logistic regression. RESULT: Of the total households visited, 293(29%) stored drugs. The mean number of drugs per household was 1.73. The most common classes of drugs found in households were analgesics 149(29%) and antibiotics 128(25%). Most of the medicines kept in households were used for ongoing treatments 316(62%) and available in tablet dosage form (70%). More than half of the medications kept at homes were not adequately labeled while drawer 180(36%) were reported as the main place of drug storage. The proportion of home storage of medicines in rural area (AOR = 0.56, 95% CI: 0.39-0.81) was lower than that of urban area. However, households having family member(s) working in health facilities (AOR = 2.03, 95% CI: 1.09-3.77) were associated with an increased home storage of medicines. CONCLUSION: Most drugs kept at home were not appropriately labeled and stored in a safe place. Residence area (rural versus urban) and the presence of health professional(s) in the households affects household drug storage. Hence, public education campaign should be considered as an intervention to improve the storage condition of medicines in the households. PMID- 26275058 TI - Content Volatility of Scientific Topics in Wikipedia: A Cautionary Tale. AB - Wikipedia has quickly become one of the most frequently accessed encyclopedic references, despite the ease with which content can be changed and the potential for 'edit wars' surrounding controversial topics. Little is known about how this potential for controversy affects the accuracy and stability of information on scientific topics, especially those with associated political controversy. Here we present an analysis of the Wikipedia edit histories for seven scientific articles and show that topics we consider politically but not scientifically "controversial" (such as evolution and global warming) experience more frequent edits with more words changed per day than pages we consider "noncontroversial" (such as the standard model in physics or heliocentrism). For example, over the period we analyzed, the global warming page was edited on average (geometric mean +/-SD) 1.9+/-2.7 times resulting in 110.9+/-10.3 words changed per day, while the standard model in physics was only edited 0.2+/-1.4 times resulting in 9.4+/-5.0 words changed per day. The high rate of change observed in these pages makes it difficult for experts to monitor accuracy and contribute time-consuming corrections, to the possible detriment of scientific accuracy. As our society turns to Wikipedia as a primary source of scientific information, it is vital we read it critically and with the understanding that the content is dynamic and vulnerable to vandalism and other shenanigans. PMID- 26275059 TI - A Cost-Effectiveness Analysis of a Home-Based HIV Counselling and Testing Intervention versus the Standard (Facility Based) HIV Testing Strategy in Rural South Africa. AB - INTRODUCTION: There is growing evidence concerning the acceptability and feasibility of home-based HIV testing. However, less is known about the cost effectiveness of the approach yet it is a critical component to guide decisions about scaling up access to HIV testing. This study examined the cost effectiveness of a home-based HIV testing intervention in rural South Africa. METHODS: Two alternatives: clinic and home-based HIV counselling and testing were compared. Costs were analysed from a provider's perspective for the period of January to December 2010. The outcome, HIV counselling and testing (HCT) uptake was obtained from the Good Start home-based HIV counselling and testing (HBHCT) cluster randomised control trial undertaken in KwaZulu-Natal province. Cost effectiveness was estimated for a target population of 22,099 versus 23,864 people for intervention and control communities respectively. Average costs were calculated as the cost per client tested, while cost-effectiveness was calculated as the cost per additional client tested through HBHCT. RESULTS: Based on effectiveness of 37% in the intervention (HBHCT) arm compared to 16% in control arm, home based testing costs US$29 compared to US$38 per person for clinic HCT. The incremental cost effectiveness per client tested using HBHCT was $19. CONCLUSIONS: HBHCT was less costly and more effective. Home-based HCT could present a cost-effective alternative for rural 'hard to reach' populations depending on affordability by the health system, and should be considered as part of community outreach programs. PMID- 26275063 TI - "Two-Step" Raman Imaging Technique To Guide Chemo-Photothermal Cancer Therapy. AB - Graphene oxide-wrapped gold nanorods (GO@AuNRs) offer efficient drug delivery as well as NIR laser photothermal therapy (PTT) in vitro and in vivo. However, no real-time observation of drug release has been reported to better understand the synergy of chemotherapy and PTT. Herein, surface-enhance Raman spectroscopy (SERS) is employed to guide chemo-photothermal cancer therapy by a two-step mechanism. In the presence of GO as an internal standard, SERS signals of DOX (doxorubicin) loaded onto GO@AuNRs are found to be pH-responsive. Both DOX and GO show strong SERS signals before the DOX@GO@AuNRs are endocytic. However, when the DOX@GO@AuNRs enter acidic microenvironments such as endosomes and/or lysosomes, the DOX signals start decreasing while the GO signals remain the same. This plasmonic antenna could be used to identify the appropriate time to apply the PTT laser during chemo-photothermal therapy. PMID- 26275060 TI - Long-Term Outcomes and Prognostic Factors of Trabeculectomy following Intraocular Bevacizumab Injection for Neovascular Glaucoma. AB - PURPOSE: To evaluate long-term outcomes and identify prognostic factors of trabeculectomy following intraocular bevacizumab injection for neovascular glaucoma. METHODS: Sixty-one eyes of 54 patients with neovascular glaucoma treated by trabeculectomy following intraocular bevacizumab injection were consecutively enrolled. Surgical success criteria were sufficient intraocular pressure (IOP) reduction (IOP <= 21 mmHg, >= 20% IOP reduction, no additional medications or glaucoma surgeries) without devastating complications (loss of light perception, phthisis bulbi, and endophthalmitis) or significant hypotony (IOP <= 5 mmHg continued >= 6 months and until the last follow-up visit or hypotony requiring intervention). Kaplan-Meier survival curves and Cox regression analysis were used to examine success rates and risk factors for surgical outcomes. RESULTS: The follow-up period after trabeculectomy was 45.0 +/- 22.2 months (mean +/- standard deviation). Surgical success rate was 86.9 +/- 4.3% (+/ standard error), 74.0 +/- 6.1%, and 51.3 +/- 8.6% at 1, 3, and 5 years. Multivariate Cox regression analysis identified two risk factors; lower preoperative IOP (<= 30 mmHg) for surgical failure and hypotony [hazard ratio (HR), 2.92, 6.64; 95% confidence interval (CI), 1.22 to 7.03, 1.47 to 30.0; P = 0.018, 0.014, respectively], and vitrectomy after trabeculectomy for surgical failure with or without hypotony criteria (HR, 2.32, 4.06; 95% CI, 1.02 to 5.28, 1.30 to 12.7; P = 0.045, 0.016, respectively). CONCLUSIONS: The long-term outcomes of trabeculectomy following intraocular bevacizumab injection for neovascular glaucoma were favorable. Lower baseline IOP was associated with development of significant hypotony, while additional vitrectomy was related to insufficient IOP reduction. PMID- 26275064 TI - Impact of Sense of Coherence on Oral Health Behaviors: A Systematic Review. AB - OBJECTIVES: The aim of this review was to critically analyze the empirical evidence on the association between Sense of Coherence (SOC) and oral health behaviors through a systematic approach. METHODS: A systematic search up to April 2015 was carried out using the following electronic bibliographic databases: PubMed, Ovid MEDLINE; ISI Web of Science; and Ovid PsychInfo. Studies were included if they evaluated the relationship between SOC and oral health behaviors including tooth cleaning, fluoride usage, dietary habits, dental attendance, and smoking. We excluded studies that only assessed the relationship between oral health status and SOC without evaluating oral health behaviors. The New Castle Ottawa (NOS) quality assessment checklist was employed to evaluate the methodological quality of included studies. RESULTS: Thirty-nine potential papers met the preliminary selection criteria and following a full-text review, 9 papers were finally selected for this systematic review. Results provided by the included studies indicated different levels of association between SOC and oral health behaviors. The most frequent behaviors investigated were tooth brushing and dental attendance pattern. The impact of SOC on performing positive oral health behaviors, to some extent, was related to demographic and socio-economic factors. In addition, mothers' SOC influenced children's oral health practices. CONCLUSIONS: A more favorable oral health behavior was observed among those with a stronger SOC suggesting that the SOC can be a determinant of oral health related behaviors including tooth brushing frequency, daily smoking, and dental attendance. PMID- 26275065 TI - Age-Related Left Ventricular Changes and Their Association with Leukocyte Telomere Length in Healthy People. AB - INTRODUCTION: With advancing age the left ventricle (LV) undergoes structural and functional changes, thereby creating the substrate for the development of diseases. One possible mechanism of the ageing heart is a cellular senescence. Leukocyte telomere length (LTL) is a marker of replicative ageing. The purpose of this study was to evaluate the structure and function of the LV in people of different ages free of cardiovascular diseases (CVD) and regular drug medication and to assess their relationship with LTL. We hypothesized that age-related changes in LV myocardium are associated with telomere length. METHODS: The study population consisted of 150 healthy, non-obese volunteers aged 28 to 78 years without history of CVD, significant deviations by 12-lead electrocardiogram and negative exercise test (treadmill stress test). All the participants underwent standardized transthoracic echocardiography using an available system (iE33; Philips). The LTL was measured by real-time quantitative polymerase chain reaction. We determined the relative ratio of telomere repeat copy number (T) to single-copy gene copy number (S). RESULTS: In the older people there was a higher wall thickness than in the younger (1.03 +/- 0.09 vs. 0.88 +/- 0.10, p<0.01), whereas LV mass index was comparable between them (85.8 +/- 15.40 vs. 83.1 +/- 11.8, p = 0.20). There was a decrease in LV dimensions with advancing age (p<0.001). Older subjects had impairment in LV relaxation. LTL was associated with decreased E/A, Em/Am ratio (beta = -0.323, p = 0.0001) after adjusting for age, sex and risk factors. There is no relation between the LTL and the structure of LV. CONCLUSIONS: Our data suggest that the ageing process leads to changes in LV structure and diastolic function and is linked with a phenotype of concentric LV remodeling. Telomere attrition is associated with age-related LV diastolic dysfunction. Telomere length appears to be a biomarker of myocardial ageing. PMID- 26275066 TI - Current Trends in Theoretical Orientation of Psychologists: The Case of Quebec Clinicians. AB - OBJECTIVE: Trends indicate that clinical psychologists' theoretical orientations have changed over the last decades in North America, but research on this topic in Canada is scarce. We analyzed the orientation of psychologists over the last 20 years in the province of Quebec, where 46% of Canadian psychologists are located. METHOD: Data were collected annually through the board registration form of Quebec psychologists' professional order from 1993 to 2013. Univariate statistical analyses were realized on aggregated data. RESULTS: In 20 years, the proportion of clinicians choosing cognitive-behavioral therapy (CBT) as their main orientation grew from 18.4% to 38%, while preference for other orientations slightly declined. Existential-humanistic and psychodynamic-psychoanalytic approaches remained the primary orientation for around 21.7% and 21.5%, respectively. In 2013 (N = 8608), when taking into account 2 choices of theoretical orientation, 55.8% of clinicians chose CBT, 34.3% existential humanistic orientation, 27.9% psychodynamic-analytic theories, and 21.8% systemic interactional orientation. CONCLUSIONS: Findings underline trends in Quebec clinical practice characterized by an increase in the number of psychologists identifying cognitive-behavioral approach as their primary self-reported theoretical orientation. PMID- 26275067 TI - Relearning knowledge for people in a case of right variant frontotemporal dementia. AB - Right variant frontotemporal dementia (Rvt-FTD) is a rare variant of FTD that usually presents with a progressive difficulty in recognizing familiar people. We aimed to determine whether rehabilitation of semantic knowledge for people improves recognition by both verbal and visual channels in a patient with Rvt FTD. Knowledge for 21 famous people was assessed in a patient with Rvt-FTD before and after completing a semantic rehabilitation program. After rehabilitation recognition increased by 95% when presented with the famous people's names and related semantic facts, but only by 28% when presented with their faces. Recognition of people by verbal and visual channels improves differently after semantic knowledge rehabilitation. PMID- 26275068 TI - Association of Mucosal Organisms with Patterns of Inflammation in Chronic Rhinosinusitis. AB - BACKGROUND: Chronic rhinosinusitis is a multifactorial process disease in which bacterial infection or colonization may play an important role in the initiation or persistence of inflammatory response. The association between mucosal bacteria presence and inflammatory patterns has only been partially explored. OBJECTIVE: To demonstrate specific mucosal microorganisms possible association with inflammatory patterns. METHODS: We collected nasal polyps or sinus tissues from a clinical selection of six patient groups with defined sinus disease using tissue biomarkers. In the tissues, we detected bacteria using peptide nucleic acid fluorescence in situ hybridization (PNA-FISH). RESULTS: After reviewing a total of 115 samples (15-20 samples per group), the mucosal presence of Staphylococcus aureus was correlated with IL-5 and SE-IgE positive chronic rhinosinusitis with nasal polyps and nasal polyps from cystic fibrosis patients. Chronic rhinosinusitis without nasal polyps with TNFalpha >20 pg/ml was associated with the mucosal presence of Pseudomonas aeruginosa. CONCLUSION: This study identifies the relationship between intramucosal microbes and inflammatory patterns, suggesting that bacteria may affect the type of inflammation in chronic rhinosinusitis. Additional investigation is needed to further identify the nature of the relationship. PMID- 26275069 TI - Does recall of a past music event invoke a reminiscence bump in young adults? AB - Many studies of the reminiscence bump (RB) in music invoke memories from different autobiographical times by using stimulus specific prompts (SSPs). This study investigated the utility of a non-SSP paradigm to determine whether the RB would emerge when participants were asked to recall a single memorable musical event from "a time long ago". The presence of a RB in response to music has not been obtained in such a manner for younger participants. Eighty-eight 20-22 year olds reported music episodes that peaked when their autobiographical age was 13 14 years. Self-selected stimuli included a range of musical styles, including classical and non-Western pop forms, such as J-pop and K-pop, as well as generational pop music, such as the Beatles. However, most participants reported pop/rock music that was contemporaneous with encoding age, providing support for the utility of published SSP paradigms using pop music. Implications for and limitations of SSP paradigms are discussed. Participants were also asked to relate the selected musical piece to current musical tastes. Most participants liked the music that they selected, with many continuing to like the music, but most also reported a general broadening of their taste, consistent with developmental literature on open-earedness. PMID- 26275070 TI - Patient-defined goals for the treatment of severe aortic stenosis: a qualitative analysis. AB - BACKGROUND: Patients with severe aortic stenosis (AS) at high risk for aortic valve replacement are a unique population with multiple treatment options, including medical therapy, surgical aortic valve replacement and transcatheter aortic valve replacement (TAVR). Traditionally, in elderly populations, goals of treatment may favour quality of life over survival. Professional guidelines recommend that clinicians engage patients in shared decision making, a process that may lead to decisions more aligned with patient-defined goals of care. Goals of care for high-risk patients with AS are not well defined in the literature, and patient-reported barriers to shared decision making highlight the need for explicit encouragement from clinicians for patient involvement. OBJECTIVE: The purpose of this study was to elicit and report patient-defined goals from elderly patients facing treatment decisions for severe AS. METHODS: This analysis was conducted at Dartmouth-Hitchcock Medical Center, an academic medical institution. In a retrospective manner, we qualitatively analysed goal statements reported by high-risk, elderly patients with severe AS evaluated for TAVR between June 2012 and August 2014. RESULTS: Forty-six patients provided treatment goals during consideration of TAVR and defined preferred outcomes as maintaining independence, staying alive, reducing symptoms or, most commonly, increasing their ability to do a specific activity or hobby. CONCLUSIONS: In the high-risk patient population considering TAVR, patient-reported goals may be obtained with a simple question delivered during the clinical encounter. Encouraging patients to define their goals may lead to a greater degree of shared decision making, as advocated in current professional guidelines. PMID- 26275072 TI - A trinuclear Cu(II) complex with functionalized s-heptazine N-ligands: molecular chemistry from a g-C3N4 fragment. AB - A new kind of N-ligand based on heptazine derivatives is presented. A trinuclear Cu(II) complex, [(L)2CuCl3](ClO4)3.3CH2Cl2 (L = 2,4,6-tris(di-2 pyridylamino)heptazine), utilizing a pyridine derivative of heptazine has been synthesized and characterized avoiding the inherent solubility problems of heptazine compounds. Thus, this work opens the application of such ligands either in supramolecular chemistry as a larger ligand of the widely used s-triazine derivatives or to provide molecular systems for photocatalysis as heptazine is the fundamental unit of the very promising g-C3N4 2D compound. PMID- 26275071 TI - Hydroxyurea Therapy for Children With Sickle Cell Anemia in Sub-Saharan Africa: Rationale and Design of the REACH Trial. AB - BACKGROUND: Sickle cell anemia (SCA) is an inherited hematological disorder that causes a large but neglected global health burden, particularly in Africa. Hydroxyurea represents the only available disease-modifying therapy for SCA, and has proven safety and efficacy in high-resource countries. In sub-Saharan Africa, there is minimal use of hydroxyurea, due to lack of data, absence of evidence based guidelines, and inexperience among healthcare providers. PROCEDURE: A partnership was established between investigators in North America and sub Saharan Africa, to develop a prospective multicenter research protocol designed to provide data on the safety, feasibility, and benefits of hydroxyurea for children with SCA. RESULTS: The Realizing Effectiveness Across Continents with Hydroxyurea (REACH, ClinicalTrials.gov NCT01966731) trial is a prospective, phase I/II open-label dose escalation study of hydroxyurea that will treat a total of 600 children age 1-10 years with SCA: 150 at each of four different clinical sites within sub-Saharan Africa (Angola, Democratic Republic of Congo, Kenya, and Uganda). The primary study endpoint will be severe hematological toxicities that occur during the fixed-dose treatment phase. REACH has an adaptive statistical design that allows for careful assessment of toxicities to accurately identify a safe hydroxyurea dose. CONCLUSIONS: REACH will provide data that address critical gaps in knowledge for the treatment of SCA in sub-Saharan Africa. By developing local expertise with the use of hydroxyurea and helping to establish treatment guidelines, the REACH trial results will have the potential to transform care for children with SCA in Africa. PMID- 26275073 TI - Co-exposure of ZnO nanoparticles and UV radiation to Daphnia magna and Danio rerio: Combined effects rather than protection. AB - The application of nanoparticles (NPs) in consumer products has been increasing over the past few years. Their release into the environment is likely to happen at any stage of production or during the use of products containing NPs. Zinc oxide NPs (ZnO-NP) are among the most-used NPs on the market due to its intrinsic properties, such as ultraviolet (UV) absorption. The aim of the present study was to assess the combined effects of ZnO-NP and UV radiation on 2 freshwater species: Daphnia magna and Danio rerio. The initial hypothesis was that the presence of ZnO-NP in the aquatic media would decrease the damaging effects of UV radiation for both species. The endpoints assessed for D. magna were immobilization, feeding inhibition, and reproduction output. For D. rerio, egg development was studied during 96 h and mortality, hatching delay, and abnormal development were the endpoints recorded. Combined exposures were designed based on the single toxicity of both stressors and analyzed based on the independent action concept and exploring possible deviations for synergism/antagonism, dose level, and dose ratio. Combined exposures with D. magna induced synergism on reproduction, decreasing the number of neonates produced more than expected based on both stressors' individual toxicity. Single exposures of D. rerio embryos to both stressors induced negative effects. The combined exposures caused a dose ratio deviation pattern on mortality and hatching, with a synergism observed when ZnO-NP was the dominant stressor, changing to antagonism when UV radiation dominated the combined exposure. Regarding the results attained, studying ZnO toxicity under laboratory conditions may underestimate the risks when considering the potential interaction on effects when combined with UV radiation. PMID- 26275074 TI - Diastereoselective synthesis of pitavastatin calcium via bismuth-catalyzed two component hemiacetal/oxa-Michael addition reaction. AB - An efficient and concise asymmetric synthesis of pitavastatin calcium (1) starting from commercially available (S)-epichlorohydrin is described. A convergent C1 + C6 route allowed for the assembly of the pitavastatin C7 side chain via a Wittig reaction between phosphonium salt 2 and the enantiomerically pure C6-formyl side chain 3. The 1,3-syn-diol acetal motif in 3 was established with excellent stereo control by a diastereoselective bismuth-promoted two component hemiacetal/oxa-Michael addition reaction of (S)-alpha,beta-unsaturated ketone 4 with acetaldehyde. PMID- 26275076 TI - MicroRNA-150: A potential regulator in pathogens infection and autoimmune diseases. AB - MicroRNAs (miRNAs) are short non-coding RNAs that play an important role in post transcriptional regulation of gene expression. The past studies showed that miR 150 might emerge as a master regulator of gene expression during the immune cells differentiation and immune response process. Its regulation ability in immune cellular process might contribute to the host defense against invading pathogens, and dysregulated expression of miR-150 in immune cells might result in autoimmune diseases. This review summarized that miR-150 could regulate B cells, T cells and NK/iNKT cells differentiation and immune response. And also, this review provides a comprehensive view on the association of miR-150 and autoimmune diseases such as systemic sclerosis (SSc), multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus and contact sensitivity. Especially, the duplex role of miR 150 in the fibrosis process might contribute to the pathomechanism of SSc. Though much remains to be explored about the roles of miR-150 in pathogenic infection and autoimmune diseases, targeting miR-150 may serve as a promising therapy strategy. PMID- 26275075 TI - Metabolic Syndrome Components are Associated with Increased Prostate Cancer Risk. AB - BACKGROUND: Our study investigated the associations of metabolic syndrome (MS) and metabolic indicators with prostate cancer (PCa) risk in the Chinese Han ethnic population. MATERIAL AND METHODS: We studied 101 PCa patients (without/with MS) and 120 healthy controls. Clinical data, including waist circumference, BMI, TG, FINS, FBG, and PCa-related indicators, were collected. The correlations between MS and PCa were analyzed. RESULTS: Compared to PCa, PV and Gleason scores increased and PSA levels decreased in PCa with MS group (all P<0.001). PV was positively correlated with BMI, FINS, and HOMA-IR (r=0.459, P<0.001; r=0.421, P=0.001; r=0.490, P=0.003, respectively), and was negatively correlated with HDL-C (r=-0.378, P<0.001). PSA level in MS patients was negatively correlated with BMI (r=-0.125, P<0.001), TG (r=-0.256, P<0.001) and FBG (r=-0.183, P<0.001). Large PV, high TG, low HDL-C, high LDL-C, and high FBG were associated with an increased risk of PCa (P<0.001, OR=1.10, 95%CI: 1.009 3.304; P<0.001, OR=2.91, 95%CI: 1.612-5.241; P<0.001, OR=7.89, 95%CI: 3.908 15.947; P=0.015, OR=1.87, 95%CI: 1.131-3.077; P=0.004, OR=2.17, 95%CI: 1.280 3.686, respectively). MS-related indicators showed a positive relationship with PCa (P<0.001, OR=1.90, 95%CI: 1.107-10.629). CONCLUSIONS: Our study shows that MS and metabolic indicators are associated with an increased risk of PCa, pointing to a novel therapeutic approach for PCa management. PMID- 26275077 TI - Abnormal lipid rafts related ganglioside expression and signaling in T lymphocytes in immune thrombocytopenia patients. AB - Aberrant T lymphocytes signaling is considered to play a crucial role in the abnormal immune state of primary immune thrombocytopenia (ITP). Lipid raft has been verified to engage in the T cell receptor (TCR)-mediated T lymphocytes signal transduction. Whether lipid raft-associated T cells signal transduction has impact on the pathogenesis of ITP is still unconfirmed. In this study, we aimed to reveal the abnormality in structure and function of lipid rafts (LRs) in CD4+ and CD8+ T lymphocytes of patients with ITP. Our results showed that there was an increased lipid raft aggregation in ITP patients, while this kind of increase would not be influenced by platelet counts or therapeutic regimes. Stimulation by anti-CD3/CD28 monoclonal antibodies promoted enhanced lipid raft clustering in T lymphocytes of ITP patients compared with negative controls. Methyl-beta-cyclodextrin (MbetaCD) could block the abnormal lipid raft aggregation and disrupt the TCR-mediated T cells proliferation and cytokines secretion, including both proinflammatory cytokines and anti-inflammatory cytokines. The spontaneous activation of T lymphocytes from ITP patients might be due to the elevated co-localization of protein tyrosine phosphatase (PTP) CD45 and lipid rafts in patients' CD4+ and CD8+ T lymphocytes. These findings suggest that the autoactivation of T lymphocytes from ITP patients may lead to the abnormality in lipid raft structure and raft-anchored proteins, and the changes conversely promote the TCR-mediated T cells activation of ITP patients. PMID- 26275078 TI - Immunization of mice with a peptide derived from the HTLV-1 TAX1BP1 protein induces cross-reactive antibodies against aquaporin 4. AB - Antibodies against aquaporin-4 (AQP4) are specific and pathogenetic for Neuromyelitis Optica (NMO). In a previous study, three linear intracellular AQP4 B-cell epitopes were uncovered in NMO patients. A particular epitope showed high sequence similarity with a segment of the human TAX1BP1 protein, which is necessary for the replication of HTLV-1 virus. The aim of the present study was to investigate whether immunization of mice with the TAX1BP1 peptide could produce specific antibodies against AQP4 epitopes or induce symptoms. Eight C57Bl/6 mice were immunized with TAX1BP1pep in Complete Freund's Adjuvant and eight with adjuvant only. Animals received three subcutaneous injections and sera were obtained before each immunization and at sacrifice. All sera were evaluated by ELISA for antibodies against the TAX1BP1peptide, the homologous AQP4 peptide and all linear AQP4 epitopes. Homologous and cross-inhibition assays were performed to ensure binding specificity, and reactivity against conformational AQP4 epitopes was evaluated by a cell-based assay. Sera from immunized animals showed high reactivity against the immunization peptide, and the homologous AQP4 epitope. Inhibition assays confirmed binding specificity. No antibodies were produced against any other epitopes, either linear or conformational. No clinical or brain inflammatory signs were observed in the animals. The induction of antibodies to an AQP4 epitope in mice immunized with the TAX1BP1-derived peptide suggests that a latent HTLV-1 infection could lead to TAX1BP1 antigen presentation and the production of anti-AQP4 antibodies, probably through T cell mediated mechanisms. Further studies are needed for exploring triggering factors for NMO especially in HTLV-1-endemic regions. PMID- 26275079 TI - Adding Value to Palliative Care Services: The Development of an Institutional Bereavement Program. AB - BACKGROUND: Although bereavement programs are a common element of palliative medicine and hospice programs, few health care institutions currently offer universal bereavement services to all their patients. The elevated risk of serious physical and mental health problems among the bereaved is a strong argument for the development of universal institution-based bereavement programs as an element of quality care for family members of all patients who die. OBJECTIVE: We describe the development of the bereavement program at Dana-Farber Cancer Institute (DFCI) where we conceptualized bereavement services as a preventive model of care. DESIGN: We identified education, guidance and support as the primary constructs of the program. The essential components include a formal acknowledgement of the death of the patient by the cancer center, information about grief and what to expect, individual visits to assess coping, and staff support and education. SUBJECTS: One hundred and forty bereaved families completed a survey about the bereavement program. RESULTS: The findings indicated that the formal letter of condolence and the bereavement guide had a positive impact on the grieving of the respondents. Contact from the patient's oncologist and nurse was especially well received. CONCLUSIONS: Bereavement programs can both help bereaved individuals adapt to their loss, and positively impact hospitals by enhancing the reputation of the hospital within the community and providing an avenue for identifying opportunities for improvement in care processes. We recommend that all hospitals implement basic bereavement programs for families of all deceased patients as the standard of care. PMID- 26275081 TI - Cardiovascular events in chronic hepatitis C: prognostic value of liver stiffness evolution. AB - BACKGROUND AND AIMS: Chronic hepatitis C is also a metabolic disease that may increase cardiovascular events. FibroScan is a diagnostic tool for fibrosis and a prognostic tool for cirrhosis complications and mortality. The aim of our study was to investigate the prognostic value of liver stiffness evolution and initial stiffness in cardiovascular events occurring in patients with chronic hepatitis C. PATIENTS AND METHODS: Between 2006 and 2013, chronic hepatitis C patients followed in a reference center with two valid liver stiffness measurements by FibroScan were included. Cardiovascular events occurring after the initial FibroScan were collected retrospectively. 'Rapid stiffness progression' was defined as an evolution of at least 0.3 kPa/year and 'high initial stiffness' as at least 7 kPa. RESULTS: Among 561 patients with chronic hepatitis C, 135 were included, mean follow-up 5.2 years, 56% men, mean age 55.3 years, infected with genotype 1 (71%). Among these, 27 were overweight, 12 had type 2 diabetes, 41 had steatosis, and 89 had been treated. During follow-up, seven patients had a cardiovascular event (four myocardial infarctions, three strokes). Among the 35 patients with rapid stiffness progression, 6% had a cardiovascular event compared with 5% of 100 patients with slow progression (P=1.0). Among the 57 patients with high initial stiffness, 11% had a cardiovascular event compared with 1% of the 78 patients with low initial stiffness (P=0.04). CONCLUSION: In chronic hepatitis C, initial stiffness of at least 7 kPa was associated with cardiovascular events. Rapid progression of liver stiffness does not seem to be associated with these events. PMID- 26275080 TI - Phase 2 trial of ixazomib in patients with relapsed multiple myeloma not refractory to bortezomib. AB - This phase 2 trial was designed to evaluate ixazomib, an orally bioavailable proteasome inhibitor, in patients with myeloma who have limited prior exposure to bortezomib. Thirty-three patients with relapsed multiple myeloma were enrolled. Ixazomib was given at 5.5 mg weekly for 3 of 4 weeks. Dexamethasone was added for lack of a minor response (MR) by end of cycle 2 or lack of a partial response (PR) by end of cycle 4 or for disease progression at any time. Median age was 69 years; patients had a median of two prior therapies (range 1-7). A grade 3 or 4 adverse event considered at least possibly related to drug was seen in 19 (59%) and 6 (19%) patients, respectively. The most common adverse events were thrombocytopenia, fatigue, nausea and diarrhea. Dexamethasone was initiated in 22 (67%) patients, 17 for not reaching the desired response and 5 for progression. Response (?PR) to single agent was seen in five patients within four cycles of therapy including three patients with PR, one patient with complete response (CR) and one patient with stringent CR. Six additional patients with either an MR (2) or SD (4) achieved a PR after addition of dexamethasone, translating to an overall response rate of 34%. PMID- 26275082 TI - King's score as a novel prognostic model for patients with hepatitis B-associated hepatocellular carcinoma. AB - BACKGROUND AND OBJECTIVES: King's score (KS) has been developed to predict the presence of cirrhosis and hepatocellular carcinoma (HCC) in patients with chronic liver diseases. We aimed to investigate the prognostic significance of the KS in hepatitis B-associated HCC. PATIENTS AND METHODS: We retrospectively analyzed 319 hepatitis B-associated HCC patients. Preoperative data were collected to calculate the KS (age * aspartate aminotransferase * international normalized ratio/platelet count). The primary outcomes were overall survival (OS) and disease-free survival (DFS), which was estimated using the Kaplan-Meier method. Then, we carried out a multivariate Cox analysis to assess the independent significance of the KS. Additional analyses were carried out after patients were stratified on the basis of cirrhosis status and therapy methods to investigate the significance of KS in different subgroups. RESULTS: During a median follow-up period of 44 months, 199 (62.4%) patients died and 144 (45.1%) experienced recurrence. The cut-off value for the KS was determined to be 33.31 with 56.8% sensitivity and 66.7% specificity. Compared with patients with low KS, the high group showed a higher probability of cirrhosis and worse Child-Pugh class (both P<0.05). Multivariate analysis identified older age, tumor size 5 or more, palliative therapy, high Barcelona Clinic Liver Cancer stage, and high KS as significant factors for predicting poor OS and DFS. A combination of the KS and tumor size showed better discrimination ability for survival than Barcelona Clinic Liver Cancer stage. CONCLUSION: The KS is an effective index for predicting OS and DFS in hepatitis B-associated HCC. Larger cohorts are needed to validate our finding. PMID- 26275083 TI - A retrospective study assessing fully covered metal stents as first-line management for malignant biliary strictures. AB - OBJECTIVES: Fully covered self-expanding metal stents (FCSEMS) constitute the first type of metal stent that can easily be removed endoscopically and/or intraoperatively, which may be advantageous in the management of distal malignant biliary strictures (DMBS). To assess the efficacy of FCSEMS as first-line treatment for DMBS, we compared patency, survival and complication rates between FCSEMS, uncovered self-expanding metal stents (USEMS) and plastic stents (PS). METHODS: This was a multicentre retrospective study of 315 consecutive patients with DMBS, who underwent endoscopic retrograde cholangiopancreatography and stenting (FCSEMS, USEMS or PS) at two hospitals between 1 January 2007 and 31 December 2013. Stent patency and patient survival were compared using the Kaplan Meier method; complication rates were compared using Fisher's exact test; and Cox regression analysis was used to screen for confounding factors. RESULTS: FCSEMS were associated with prolonged stent patency (median=145 days) compared with USEMS (median=110 days, P<0.003) and PS (median=34 days, P<0.001). Biliary sepsis rates were lower for FCSEMS compared with PS (4.7 vs. 17.8%, P=0.02), whereas pancreatitis rates were higher for FCSEMS compared with USEMS (7.8 vs. 1.0%, P=0.04), but not PS (2.6%, P=NS). CONCLUSION: The use of FCSEMS as first-line management for DMBS is associated with longer patency and reduced complication rates compared with the use of PS. However, the higher rate of pancreatitis compared with USEMS requires further evaluation in a large randomized controlled trial. PMID- 26275084 TI - Ki67 as a prognostic factor for long-term outcome following surgery in gastrointestinal stromal tumors. AB - OBJECTIVE: This study aimed to examine the value of Ki67 expression along with other potential prognostic factors for predicting overall survival and disease free survival in patients with gastrointestinal stromal tumors who underwent curative resection. PATIENTS AND METHODS: Sixty-eight histologically confirmed and operated patients with gastrointestinal stromal tumors were included. Clinical and follow-up data were retrieved from medical records and patients were contacted at the end of the study. The effects of certain clinical and histopathological parameters on survival outcomes were examined. RESULTS: Sixty eight patients were followed for a mean duration of follow-up of 2923.3 patient months. Twelve deaths (17.6%), seven metastasis (10.3%), and two local recurrences (2.9%) occurred. Overall survival was 102.5 months [95% confidence interval (CI), 88.3-116.8] and disease-free survival was 91.8 months (95% CI, 76.5-107.2). Multivariate analyses identified a high Ki67 index (>= 10%) as an independent predictor of both poor overall survival (hazard ratio, 4.8; 95% CI 1.2-19.2; P=0.027) and poor disease-free survival (hazard ratio, 15.3; 95% CI, 4.7-50.2). CONCLUSION: A high Ki67 expression seems to be a useful prognostic factor that would aid in predicting disease course in gastrointestinal stromal tumors. These findings deserve further investigation in larger studies. PMID- 26275085 TI - Infliximab for the treatment of Crohn's disease: efficacy and safety in a Chinese single-center retrospective study. AB - BACKGROUND AND AIM: Information describing the efficacy and safety of infliximab (IFX) for Crohn's disease (CD) in China is limited. The aim of this study was to report response rates, relapse rates after IFX-induced remission, and adverse events, and identify factors associated with relapse in a cohort of CD patients treated with IFX in a Chinese center. PATIENTS AND METHODS: Clinical data of CD patients treated with two or more infusions of IFX from July 2010 to February 2013 at Nanfang Hospital (Guangzhou, China) were retrieved and analyzed retrospectively. Primary measurements were clinical response rate and relapse rate during 30 weeks of follow-up. Overall adverse events and risk factors related to IFX were evaluated. RESULTS: A total of 70 CD patients were finally included. The clinical response rate was 98.6% at week 2, 97% at week 6, 92.5% at week 14, 84.9% at week 22, and 84.1% at week 30. The remission rate was 55.7% at week 2, 94% at week 6, 92.5% at week 14, 82.7% at week 22, and 77.3% at week 30. Relapse began following the third infusion. The relapse rate was 3.23% at week 6, 6.12% at week 14, 10.53% at week 22, and 8.82% at week 30. Adverse events related to IFX occurred in 32.6% of patients; most were mild and transient. Univariate analysis showed that sex was a significant predictor of clinical relapse. CONCLUSION: IFX is an effective and safe treatment for CD in Chinese patients. Sex may be an independent predictor of relapse. PMID- 26275086 TI - Ten years of hospital admissions for liver cirrhosis in Portugal. AB - BACKGROUND AND AIMS: More data on epidemiology of liver diseases in Europe are needed. We aimed to characterize hospital admissions for liver cirrhosis in Portugal during the past decade. PATIENTS AND METHODS: We analyzed all hospital admissions for cirrhosis in Portugal Mainland between 2003 and 2012 registered in the national Diagnosis-Related Group database. Cirrhosis was classified according to etiology considering alcohol, hepatitis B, and hepatitis C. RESULTS: Between 2003 and 2012, there were 63,910 admissions for cirrhosis in Portugal Mainland; 74.4% involved male patients. Etiologies of admitted cirrhosis were as follows: 76.0% alcoholic, 1.1% hepatitis B, 1.4% hepatitis B plus alcohol, 3.6% hepatitis C, and 4.0% hepatitis C plus alcohol. There was a significant decline (P<0.001) in admissions for alcoholic cirrhosis, whereas hospitalizations for cirrhosis caused by hepatitis C or hepatitis C plus alcohol increased by almost 50% (P<0.001). Patients admitted with alcoholic plus hepatitis B or C cirrhosis were significantly younger than those with either alcoholic or viral cirrhosis (53.1 vs. 59.4 years, respectively, P<0.001). Hospitalization rates for cirrhosis were 124.4/100,000 in men and 32.6/100,000 in women. Hepatocellular carcinoma and fluid retention were more common in viral cirrhosis, whereas encephalopathy and variceal bleeding were more frequent in alcoholic cirrhosis. Hepatorenal syndrome was the strongest predictor of mortality among cirrhosis complications (odds ratio 12.97; 95% confidence interval 11.95-14.09). In-hospital mortality was 15.2%. CONCLUSION: Despite the decline in admissions for alcoholic cirrhosis and the increase in those related to hepatitis C, the observed burden of hospitalized liver cirrhosis in Portugal was essentially attributable to alcoholic liver disease. PMID- 26275087 TI - Child abuse and neglect in complex dissociative disorder, abuse-related chronic PTSD, and mixed psychiatric samples. AB - Only a select number of studies have examined different forms of child maltreatment in complex dissociative disorders (DDs) in comparison to other groups. Few of these have used child abuse-related chronic posttraumatic stress disorder (C-PTSD) and mixed psychiatric (MP) patients with maltreatment as comparison groups. This study examined child sexual, physical, and emotional abuse as well as physical and emotional neglect in DD (n = 39), C-PTSD (n = 13), and MP (n = 21) samples, all with abuse and neglect histories. The predictive capacity of these different forms of maltreatment across the 3 groups was assessed for pathological dissociation, shame, guilt, relationship esteem, relationship anxiety, relationship depression, and fear of relationships. All forms of maltreatment differentiated the DD from the MP group, and sexual abuse differentiated the DD sample from the C-PTSD group. Childhood sexual abuse was the only predictor of pathological dissociation. Emotional abuse predicted shame, guilt, relationship anxiety, and fear of relationships. Emotional neglect predicted relationship anxiety and relationship depression. Physical neglect was associated with less relationship anxiety. Different forms of abuse and neglect are associated with different symptom clusters in psychiatric patients with maltreatment histories. PMID- 26275088 TI - Self-Assembly of an Alphavirus Core-like Particle Is Distinguished by Strong Intersubunit Association Energy and Structural Defects. AB - Weak association energy can lead to uniform nanostructures: defects can anneal due to subunit lability. What happens when strong association energy leads to particles where defects are trapped? Alphaviruses are enveloped viruses whose icosahedral nucleocapsid core can assemble independently. We used a simplest case system to study Ross River virus (RRV) core-like particle (CLP) self-assembly using purified capsid protein and a short DNA oligomer. We find that capsid protein binds the oligomer with high affinity to form an assembly competent unit (U). Subsequently, U assembles with concentration dependence into CLPs. We determined that U-U pairwise interactions are very strong (ca. -6 kcal/mol) compared to other virus assembly systems. Assembled RRV CLPs appeared morphologically uniform and cryo-EM image reconstruction with imposed icosahedral symmetry yielded a T = 4 structure. However, 2D class averages of the CLPs show that virtually every class had disordered regions. These results suggested that irregular cores may be present in RRV virions. To test this hypothesis, we determined 2D class averages of RRV virions using authentic virions or only the core from intact virions isolated by computational masking. Virion-based class averages were symmetrical, geometric, and corresponded well to projections of image reconstructions. In core-based class averages, cores and envelope proteins in many classes were disordered. These results suggest that partly disordered components are common even in ostensibly well-ordered viruses, a biological realization of a patchy particle. Biological advantages of partly disordered complexes may arise from their ease of dissociation and asymmetry. PMID- 26275089 TI - Murine Isolated Heart Model of Myocardial Stunning Associated with Cardioplegic Arrest. AB - The following protocol is of use to evaluate impaired cardiac function or myocardial stunning following moderate ischemic insults. The technique is useful for modeling ischemic injury associated with numerous clinically relevant phenomenon including cardiac surgery with cardioplegic arrest and cardiopulmonary bypass, off-pump CABG, transplant, angina, brief ischemia, etc. The protocol presents a general method to model hypothermic hyperkalemic cardioplegic arrest and reperfusion in rodent hearts focusing on measurement of myocardial contractile function. In brief, a mouse heart is perfused in langendorff mode, instrumented with an intraventricular balloon, and baseline cardiac functional parameters are recorded. Following stabilization, the heart is then subject to brief infusion of a cardioprotective hypothermic cardioplegia solution to initiate diastolic arrest. Cardioplegia is delivered intermittently over 2 hr. The heart is then reperfused and warmed to normothermic temperatures and recovery of myocardial function is monitored. Use of this protocol results in reliable depressed cardiac contractile function free from gross myocardial tissue damage in rodents. PMID- 26275090 TI - A Phase 1, Dose-escalation, Double-blind, Block-randomized, Controlled Trial of Safety and Efficacy of Neosaxitoxin Alone and in Combination with 0.2% Bupivacaine, with and without Epinephrine, for Cutaneous Anesthesia. AB - BACKGROUND: Neosaxitoxin (NeoSTX) is a site-1 sodium channel blocker that produces prolonged local anesthesia in animals and humans. Under a Food and Drug Administration-approved phase 1 Investigational New Drug trial, the authors evaluated safety and efficacy of NeoSTX alone and combined with 0.2% bupivacaine (Bup) with and without epinephrine. METHODS: The authors conducted a double blind, randomized, controlled trial involving healthy male volunteers aged 18 to 35 yr receiving two 10-ml subcutaneous injections. Control sites received Bup. In part 1, active sites received (1) 5 to 40 MUg NeoSTX+Saline (NeoSTX-Saline), (2) 5 to 40 MUg NeoSTX+Bup (NeoSTX-Bup), or (3) placebo (Saline). In part 2, active sites received 10 or 30 MUg NeoSTX+Bup+Epinephrine (NeoSTX-Bup-Epi) or placebo. Primary outcome measures were safety and adverse events associated with NeoSTX. Secondary outcomes included clinical biochemistry, NeoSTX pharmacokinetics, and cutaneous hypoesthesia. RESULTS: A total of 84 subjects were randomized and completed the two-part trial with no serious adverse events or clinically significant physiologic impairments. Perioral numbness and tingling increased with NeoSTX dose for NeoSTX-Saline and NeoSTX-Bup. All symptoms resolved without intervention. NeoSTX-Bup-Epi dramatically reduced symptoms compared with other NeoSTX combinations (tingling: 0 vs. 70%, P = 0.004; numbness: 0 vs. 60%, P = 0.013) at the same dose. Mean peak plasma NeoSTX concentration for NeoSTX-Bup-Epi was reduced at least two-fold compared with NeoSTX-Saline and NeoSTX-Bup (67 +/- 14, 134 +/- 63, and 164 +/- 81 pg/ml, respectively; P = 0.016). NeoSTX-Bup showed prolonged cutaneous block duration compared with Bup, NeoSTX-Saline, or placebo, at all doses. Median time to near-complete recovery for 10 MUg NeoSTX-Bup-Epi was almost five-fold longer compared with Bup (50 vs. 10 h, P = 0.007). CONCLUSION: NeoSTX combinations have a tolerable side effect profile and appear promising for prolonged local anesthesia. PMID- 26275091 TI - Site-1 Sodium Channel Blockers as Local Anesthetics: Will Neosaxitoxin Supplant the Need for Continuous Nerve Blocks? PMID- 26275093 TI - Measurement of wheelchair adjustment effects on turning deceleration. PMID- 26275094 TI - Fabrication of High Contrast Gratings for the Spectrum Splitting Dispersive Element in a Concentrated Photovoltaic System. AB - High contrast gratings are designed and fabricated and its application is proposed in a parallel spectrum splitting dispersive element that can improve the solar conversion efficiency of a concentrated photovoltaic system. The proposed system will also lower the solar cell cost in the concentrated photovoltaic system by replacing the expensive tandem solar cells with the cost-effective single junction solar cells. The structures and the parameters of high contrast gratings for the dispersive elements were numerically optimized. The large-area fabrication of high contrast gratings was experimentally demonstrated using nanoimprint lithography and dry etching. The quality of grating material and the performance of the fabricated device were both experimentally characterized. By analyzing the measurement results, the possible side effects from the fabrication processes are discussed and several methods that have the potential to improve the fabrication processes are proposed, which can help to increase the optical efficiency of the fabricated devices. PMID- 26275092 TI - Clinical Electroencephalography for Anesthesiologists: Part I: Background and Basic Signatures. AB - The widely used electroencephalogram-based indices for depth-of-anesthesia monitoring assume that the same index value defines the same level of unconsciousness for all anesthetics. In contrast, we show that different anesthetics act at different molecular targets and neural circuits to produce distinct brain states that are readily visible in the electroencephalogram. We present a two-part review to educate anesthesiologists on use of the unprocessed electroencephalogram and its spectrogram to track the brain states of patients receiving anesthesia care. Here in part I, we review the biophysics of the electroencephalogram and the neurophysiology of the electroencephalogram signatures of three intravenous anesthetics: propofol, dexmedetomidine, and ketamine, and four inhaled anesthetics: sevoflurane, isoflurane, desflurane, and nitrous oxide. Later in part II, we discuss patient management using these electroencephalogram signatures. Use of these electroencephalogram signatures suggests a neurophysiologically based paradigm for brain state monitoring of patients receiving anesthesia care. PMID- 26275095 TI - Application of Long-term cultured Interferon-gamma Enzyme-linked Immunospot Assay for Assessing Effector and Memory T Cell Responses in Cattle. AB - Effector and memory T cells are generated through developmental programing of naive cells following antigen recognition. If the infection is controlled up to 95 % of the T cells generated during the expansion phase are eliminated (i.e., contraction phase) and memory T cells remain, sometimes for a lifetime. In humans, two functionally distinct subsets of memory T cells have been described based on the expression of lymph node homing receptors. Central memory T cells express C-C chemokine receptor 7 and CD45RO and are mainly located in T-cell areas of secondary lymphoid organs. Effector memory T cells express CD45RO, lack CCR7 and display receptors associated with lymphocyte homing to peripheral or inflamed tissues. Effector T cells do not express either CCR7 or CD45RO but upon encounter with antigen produce effector cytokines, such as interferon-gamma. Interferon-gamma release assays are used for the diagnosis of bovine and human tuberculosis and detect primarily effector and effector memory T cell responses. Central memory T cell responses by CD4(+) T cells to vaccination, on the other hand, may be used to predict vaccine efficacy, as demonstrated with simian immunodeficiency virus infection of non-human primates, tuberculosis in mice, and malaria in humans. Several studies with mice and humans as well as unpublished data on cattle, have demonstrated that interferon-gamma ELISPOT assays measure central memory T cell responses. With this assay, peripheral blood mononuclear cells are cultured in decreasing concentration of antigen for 10 to 14 days (long term culture), allowing effector responses to peak and wane; facilitating central memory T cells to differentiate and expand within the culture. PMID- 26275096 TI - Outcomes of Orbital Blow-Out Fracture Repair Performed Beyond 6 Weeks After Injury. AB - PURPOSE: Blow-out fractures cause expansion of the bony orbital walls and prolapse of orbital contents in the sinuses. This can result in diplopia, enophthalmos, and hypoglobus. Early surgical repair has been previously recommended, however, recent reports show that delayed surgery can also be effective. In this study, the clinical and functional outcome of patients with delayed presentation and blow-out fracture repair beyond 6 weeks after injury are described. METHODS: This is a noncomparative retrospective study. Medical records of adult patients with late orbital floor fracture repair performed by 4 surgeons from April 2008 to January 2014 at 3 tertiary referral centers were reviewed. All repairs were performed more than 6 weeks from the time of injury. Patients with prior orbital fracture repair surgery were excluded. RESULTS: Twenty patients were included in the study. The duration from time of injury to surgery ranged from 7 weeks to 21 years with a mean of 19 months. Follow up ranged from 6 weeks to 56 months (mean 8 months). Mean age was 48 years (range, 25-80). Male to female ratio was 11:9. Surgery was performed on 10 right eyes and 10 left eyes. CT imaging demonstrated 10 patients had isolated floor fractures, while the remaining 10 patients had combined floor and medial wall fractures. Four patients also had associated facial fractures that did not require surgery. Indications for surgery included enophthalmos of 2 mm or more (18 of 20) and/or significant diplopia within 30 degrees of primary gaze (6 of 20). Mean pre- and postoperative enophthalmos was 2.4 +/- 0.9 mm and 0.3 +/- 0.2 mm, respectively, corresponding to a mean reduction in enophthalmos of 2.1 +/- 1.2 mm (range, 1-5 mm). Four of 7 patients with hypoglobus ranging from 1.5 mm to 8 mm preoperatively had complete resolution postoperatively, the remaining 3 patients showed reduced hypoglobus. Of the 12 patients that had diplopia preoperatively in any position of gaze, 6 patients had complete resolution of diplopia postoperatively, 4 patients had reduced but residual diplopia in extreme gaze, and 2 patients had persistent diplopia, in primary position and down gaze, respectively. Two patients had poor vision that precluded the manifestation of diplopia. None of the 6 patients without preoperative diplopia developed symptoms post operatively. CONCLUSION: Surgical repair of blow-out fractures of the orbit occurring more than 6 weeks or more from injury can achieve marked improvement in both the functional and cosmetic aspects. The likelihood of induced diplopia is low. Orbital floor fracture repair should be considered to successfully treat enophthalmos or diplopia in patients with delayed clinical presentation, even decades postinjury. PMID- 26275097 TI - Perforated Patch-clamp Recording of Mouse Olfactory Sensory Neurons in Intact Neuroepithelium: Functional Analysis of Neurons Expressing an Identified Odorant Receptor. AB - Analyzing the physiological responses of olfactory sensory neurons (OSN) when stimulated with specific ligands is critical to understand the basis of olfactory driven behaviors and their modulation. These coding properties depend heavily on the initial interaction between odor molecules and the olfactory receptor (OR) expressed in the OSNs. The identity, specificity and ligand spectrum of the expressed OR are critical. The probability to find the ligand of the OR expressed in an OSN chosen randomly within the epithelium is very low. To address this challenge, this protocol uses genetically tagged mice expressing the fluorescent protein GFP under the control of the promoter of defined ORs. OSNs are located in a tight and organized epithelium lining the nasal cavity, with neighboring cells influencing their maturation and function. Here we describe a method to isolate an intact olfactory epithelium and record through patch-clamp recordings the properties of OSNs expressing defined odorant receptors. The protocol allows one to characterize OSN membrane properties while keeping the influence of the neighboring tissue. Analysis of patch-clamp results yields a precise quantification of ligand/OR interactions, transduction pathways and pharmacology, OSNs' coding properties and their modulation at the membrane level. PMID- 26275098 TI - Effects of Lead Exposure and Genetic Polymorphisms on ALAD and GPx Activities in Brazilian Battery Workers. AB - Lead (Pb) is a toxic metal that is widely used by metallurgical industries such as car battery recycling. Exposure to the metal may modify the redox status of the cells and consequently result in changes in activities of important enzymes such as delta-aminolevulinic acid dehydratase (ALAD) and glutathione peroxidase (GPx). Similarly, genetic polymorphisms may modulate the activities of enzymes related to detoxification processes of the metal and may modify Pb body burden. Therefore, the aims of the present study were (i) to evaluate the correlation between blood lead levels (BLL) and activities of the enzymes ALAD and GPx, and (ii) to determine whether activities of these enzymes may be influenced by polymorphisms in ALAD and GPx genes in Brazilian automotive battery workers chronically exposed to Pb, as well as the effects of these polymorphisms on BLL. Our study included 257 participants; BLL were determined by inductively couple plasma-mass spectrometry (ICP-MS), and the activities of the enzymes ALAD and GPx were quantified spectrophotometrically; and genotyping of ALAD (rs1800435) and GPx-1 (rs1800668) polymorphisms was performed by TaqMan assays (real-time polymerase chain reaction, RT-PCR). Significant negative correlations were found between BLL and ALAD activity. Subjects who carried at least one polymorphic allele for ALAD gene displayed markedly lower ALAD activities, while no significant effect was observed regarding GPx-1 polymorphism and activity of the same enzyme. Further, ALAD and GPx-1 polymorphisms exerted no marked influence on BLL. Taken together, our results showed that BLL affected ALAD but not GPx activities, and these were not modulated by polymorphisms in ALAD and GPx gene. Further, the rs1800435 SNP showed a tendency to modulate ALAD activity, while the rs1800668 SNP did not modulate GPx activity in Brazilian automotive battery workers exposed to Pb. PMID- 26275099 TI - Unbiased Quantitative Models of Protein Translation Derived from Ribosome Profiling Data. AB - Translation of RNA to protein is a core process for any living organism. While for some steps of this process the effect on protein production is understood, a holistic understanding of translation still remains elusive. In silico modelling is a promising approach for elucidating the process of protein synthesis. Although a number of computational models of the process have been proposed, their application is limited by the assumptions they make. Ribosome profiling (RP), a relatively new sequencing-based technique capable of recording snapshots of the locations of actively translating ribosomes, is a promising source of information for deriving unbiased data-driven translation models. However, quantitative analysis of RP data is challenging due to high measurement variance and the inability to discriminate between the number of ribosomes measured on a gene and their speed of translation. We propose a solution in the form of a novel multi-scale interpretation of RP data that allows for deriving models with translation dynamics extracted from the snapshots. We demonstrate the usefulness of this approach by simultaneously determining for the first time per-codon translation elongation and per-gene translation initiation rates of Saccharomyces cerevisiae from RP data for two versions of the Totally Asymmetric Exclusion Process (TASEP) model of translation. We do this in an unbiased fashion, by fitting the models using only RP data with a novel optimization scheme based on Monte Carlo simulation to keep the problem tractable. The fitted models match the data significantly better than existing models and their predictions show better agreement with several independent protein abundance datasets than existing models. Results additionally indicate that the tRNA pool adaptation hypothesis is incomplete, with evidence suggesting that tRNA post-transcriptional modifications and codon context may play a role in determining codon elongation rates. PMID- 26275101 TI - Sc(OTf)3-Catalyzed [3 + 3] Cycloaddition of Cyclopropane 1,1-Diesters with Phthalazinium Dicyanomethanides. AB - The Sc(OTf)3-catalyzed diastereoselective [3 + 3] cycloaddition of phthalazinium dicyanomethanides with cyclopropane 1,1-diesters proceeded smoothly under mild reaction conditions, affording a variety of 3,4-dihydro-1H-pyrido[2,1 a]phthalazine derivatives in up to 99% yields with excellent diastereoselectivities. PMID- 26275100 TI - Adapting the Electrospinning Process to Provide Three Unique Environments for a Tri-layered In Vitro Model of the Airway Wall. AB - Electrospinning is a highly adaptable method producing porous 3D fibrous scaffolds that can be exploited in in vitro cell culture. Alterations to intrinsic parameters within the process allow a high degree of control over scaffold characteristics including fiber diameter, alignment and porosity. By developing scaffolds with similar dimensions and topographies to organ- or tissue specific extracellular matrices (ECM), micro-environments representative to those that cells are exposed to in situ can be created. The airway bronchiole wall, comprised of three main micro-environments, was selected as a model tissue. Using decellularized airway ECM as a guide, we electrospun the non-degradable polymer, polyethylene terephthalate (PET), by three different protocols to produce three individual electrospun scaffolds optimized for epithelial, fibroblast or smooth muscle cell-culture. Using a commercially available bioreactor system, we stably co-cultured the three cell-types to provide an in vitro model of the airway wall over an extended time period. This model highlights the potential for such methods being employed in in vitro diagnostic studies investigating important inter-cellular cross-talk mechanisms or assessing novel pharmaceutical targets, by providing a relevant platform to allow the culture of fully differentiated adult cells within 3D, tissue-specific environments. PMID- 26275102 TI - Differences and correlations in knee and hip mechanics during single-leg landing, single-leg squat, double-leg landing, and double-leg squat tasks. AB - Landing and squat tasks have been utilized to assess lower extremity biomechanics associated with anterior cruciate ligament loading and injury risks. The purpose of this study was to identify the differences and correlations in knee and hip mechanics during a single-leg landing, a single-leg squat, a double-leg landing, and a double-leg squat. Seventeen male and 17 female recreational athletes performed landings and squats when kinematic and kinetic data were collected. ANOVAs showed significant differences (p < 0.00001) for maximum knee flexion angles, maximum hip flexion angles, maximum knee abduction angles, maximum hip adduction angles, and maximum external knee abduction moments among squats and landings. For maximum knee and hip flexion angles, significant correlations (r >= 0.5, p <= 0.003) were observed between the two landings and between the two squats. For maximum knee abduction and hip adduction angles and maximum external knee abduction moments, significant correlations were mostly found between the two landings, and between the single-leg squat and landings (r >= 0.54, p <= 0.001). Individuals are likely to demonstrate different profiles of injury risks when screened using different tasks. While a double-leg landing should be considered as a priority in screening, a single-leg squat may be used as a surrogate to assess frontal plane motion and loading. PMID- 26275103 TI - A Simple ab Initio Model for the Hydrated Electron That Matches Experiment. AB - Since its discovery over 50 years ago, the "structure" and properties of the hydrated electron have been a subject for wonderment and also fierce debate. In the present work we seriously explore a minimal model for the aqueous electron, consisting of a small water anion cluster embedded in a polarized continuum, using several levels of ab initio calculation and basis set. The minimum energy "zero Kelvin" structure found for any 4-water (or larger) anion cluster, at any post-Hartree-Fock theory level, is very similar to a recently reported embedded DFT-in-classical-water-MD simulation (Uhlig, Marsalek, and Jungwirth, J. Phys. Chem. Lett. 2012, 3, 3071-3075), with four OH bonds oriented toward the maximum charge density in a small central "void". The minimum calculation with just four water molecules does a remarkably good job of reproducing the resonance Raman properties, the radius of gyration derived from the optical spectrum, the vertical detachment energy, and the hydration free energy. For the first time we also successfully calculate the EPR g-factor and (low temperature ice) hyperfine couplings. The simple tetrahedral anion cluster model conforms very well to experiment, suggesting it does in fact represent the dominant structural motif of the hydrated electron. PMID- 26275104 TI - Understanding deliberate practice in preschool-aged children. AB - Deliberate practice is essential for skill acquisition and expertise and may be a direct consequence of episodic foresight. However, little is known about how deliberate practice develops in children. We present two experiments testing children's ability to selectively practise a behaviour that was going to be useful in future and to reason about the role of practice in skill formation. Five-year-olds demonstrated an explicit understanding of deliberate practice both in selectively choosing to practise a future-relevant skill and in predicting skill change in others based on their practice. Four-year-olds showed some capacities, but failed to demonstrate consistent understanding of the relationship between practice and skill improvement. Children's understanding of this relationship was significantly related to their understanding of how information leads to knowledge, suggesting that both may draw on similar cognitive developmental changes. PMID- 26275105 TI - Carbamazepine versus phenytoin monotherapy for epilepsy: an individual participant data review. AB - BACKGROUND: This is an updated version of the original Cochrane review published in Issue 2, 2002 and its subsequent update in 2010.Epilepsy is a common neurological condition in which recurrent, unprovoked seizures are caused by abnormal electrical discharges from the brain. It is believed that with effective drug treatment, up to 70% of individuals with active epilepsy have the potential to become seizure-free and go into long-term remission shortly after starting drug therapy with a single antiepileptic drug in monotherapy.Worldwide, carbamazepine and phenytoin are commonly used broad spectrum antiepileptic drugs, suitable for most epileptic seizure types. Carbamazepine is a current first line treatment for partial onset seizures in the USA and Europe. Phenytoin is no longer considered a first line treatment due to concerns over adverse events associated with its use, however the drug is still commonly used in low- to middle-income countries due to it's low cost. No consistent differences in efficacy have been found between carbamazepine and phenytoin in individual trials, however the confidence intervals generated by these studies are wide. Therefore, differences in efficacy may be shown by synthesising the data of the individual trials. OBJECTIVES: To review the time to withdrawal, six- and 12 month remission, and first seizure of carbamazepine compared to phenytoin when used as monotherapy in people with partial onset seizures (simple partial, complex partial, or secondarily generalised tonic-clonic seizures) or generalised tonic-clonic seizures, with or without other generalised seizure types. SEARCH METHODS: We searched the Cochrane Epilepsy Group's Specialised Register (16 September 2014), the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 8), MEDLINE (1946 to 16 September 2014), SCOPUS (1823 to 16 September 2014), ClinicalTrials.gov (16 September 2014), and the World Health Organization (WHO) International Clinical Trials Registry Platform ICTRP (18 September 2014). We handsearched relevant journals, contacted pharmaceutical companies, original trial investigators and experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) in children or adults with partial onset seizures or generalised onset tonic-clonic seizures with a comparison of carbamazepine monotherapy versus phenytoin monotherapy. DATA COLLECTION AND ANALYSIS: This was an individual participant data (IPD) review. Our primary outcome was time to withdrawal of allocated treatment, and our secondary outcomes were time to 12 month remission, time to six-month remission and time to first seizure post randomisation. We used Cox proportional hazards regression models to obtain study specific estimates of hazard ratios (HRs) with 95% confidence intervals (CIs) and the generic inverse variance method to obtain the overall pooled HR and 95% CI. MAIN RESULTS: IPD were available for 595 participants out of 1192 eligible individuals, from four out of 12 trials (i.e. 50% of the potential data). For remission outcomes, HR > 1 indicates an advantage for phenytoin; and for first seizure and withdrawal outcomes, HR > 1 indicates an advantage for carbamazepine. Methodological quality of the four studies providing IPD was generally good and we rated it at low risk of bias overall in the analyses.The main overall results (pooled HR adjusted for seizure type) were time to withdrawal of allocated treatment: 1.04 (95% CI 0.78 to 1.39); time to 12-month remission: 1.01 (95% CI 0.78 to 1.31); time to six-month remission: 1.11 (95% CI 0.81 to 1.37); and time to first seizure: 0.85 (95% CI 0.70 to 1.04). The results suggest no overall statistically significant difference between the drugs for these outcomes. There is some evidence of an advantage for phenytoin for individuals with generalised onset seizures for our primary outcome (time to withdrawal of allocated treatment): pooled HR 0.42 (95% CI 0.18 to 0.96); and a statistical interaction between treatment effect and epilepsy type (partial versus generalised) for this outcome (P = 0.02), however misclassification of seizure type for up to 48 individuals (32% of those with generalised epilepsy) may have confounded the results of this review. Despite concerns over side effects leading to the withdrawal of phenytoin as first line treatment in the USA and Europe, we found no evidence that phenytoin is more likely to be associated with serious side effects than carbamazepine; 26 individuals withdrew from 290 randomised (9%) to carbamazepine due to adverse effects compared to 12 out of 299 (4%) randomised to phenytoin from four studies conducted in the USA and Europe (risk ratio (RR) 1.42, 95% CI 1.13 to 1.80, P = 0.014). We rated the quality of the evidence as low - moderate according to GRADE criteria, due to imprecision and potential misclassification of seizure type. AUTHORS' CONCLUSIONS: We have not found evidence that a statistically significant difference exists between carbamazepine and phenytoin for the efficacy outcomes examined in this review, however, CIs are wide and the possibility of important differences existing has not been excluded. There is no evidence in this review that phenytoin is more strongly associated with serious adverse events than carbamazepine. There is some evidence that participants with generalised seizures may be less likely to withdraw early from phenytoin than carbamazepine, but misclassification of seizure type may have impacted upon the results of this review. We recommend caution when interpreting the results of this review, and do not recommend that the results of this review alone should be used in choosing between carbamazepine and phenytoin. We recommend that future trials should be designed to the highest quality possible with considerations on allocation concealment and masking, choice of population, choice of outcomes and analysis, and presentation of results. PMID- 26275106 TI - Identification of Soft Matter Binding Peptide Ligands Using Phage Display. AB - Phage display is a powerful tool for the selection of highly affine, short peptide ligands. While originally primarily used for the identification of ligands to proteins, the scope of this technique has significantly expanded over the past two decades. Phage display nowadays is also increasingly applied to identify ligands that selectively bind with high affinity to a broad range of other substrates including natural and biological polymers as well as a variety of low-molecular-weight organic molecules. Such peptides are of interest for various reasons. The ability to selectively and with high affinity bind to the substrate of interest allows the conjugation or immobilization of, e.g., nanoparticles or biomolecules, or generally, facilitates interactions at materials interfaces. On the other hand, presentation of peptide ligands that selectively bind to low-molecular-weight organic materials is of interest for the development of sensor surfaces. The aim of this article is to highlight the opportunities provided by phage display for the identification of peptide ligands that bind to synthetic or natural polymer substrates or to small organic molecules. The article will first provide an overview of the different peptide ligands that have been identified by phage display that bind to these "soft matter" targets. The second part of the article will discuss the different characterization techniques that allow the determination of the affinity of the identified ligands to the respective substrates. PMID- 26275107 TI - Total Synthesis of Hispidulin and the Structural Basis for Its Inhibition of Proto-oncogene Kinase Pim-1. AB - A new method is applied to synthesize hispidulin, a natural flavone with a broad spectrum of biological activities. Hispidulin exhibits inhibitory activity against the oncogenic protein kinase Pim-1. Crystallographic analysis of Pim-1 bound to hispidulin reveals a binding mode distinct from that of quercetin, suggesting that the binding potency of flavonoids is determined by their hydrogen bonding interactions with the hinge region of the kinase. Overall, this work may facilitate construction of a library of hispidulin-derived compounds for investigating the structure-activity relationship of flavone-based Pim-1 inhibitors. PMID- 26275109 TI - Xenobiotic-metabolizing enzymes in plants and their role in uptake and biotransformation of veterinary drugs in the environment. AB - Many various xenobiotics permanently enter plants and represent potential danger for their organism. For that reason, plants have evolved extremely sophisticated detoxification systems including a battery of xenobiotic-metabolizing enzymes. Some of them are similar to those in humans and animals, but there are several plant-specific ones. This review briefly introduces xenobiotic-metabolizing enzymes in plants and summarizes present information about their action toward veterinary drugs. Veterinary drugs are used worldwide to treat diseases and protect animal health. However, veterinary drugs are also unwantedly introduced into environment mostly via animal excrements, they persist in the environment for a long time and may impact on the non-target organisms. Plants are able to uptake, transform the veterinary drugs to non- or less-toxic compounds and store them in the vacuoles and cell walls. This ability may protect not only plant themselves but also other organisms, predominantly invertebrates and wild herbivores. The aim of this review is to emphasize the importance of plants in detoxification of veterinary drugs in the environment. The results of studies, which dealt with transport and biotransformation of veterinary drugs in plants, are summarized and evaluated. In conclusion, the risks and consequences of veterinary drugs in the environment and the possibilities of phytoremediation technologies are considered and future perspectives are outlined. PMID- 26275108 TI - RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonself. AB - Adenosine-to-inosine (A-to-I) editing is a highly prevalent posttranscriptional modification of RNA, mediated by ADAR (adenosine deaminase acting on RNA) enzymes. In addition to RNA editing, additional functions have been proposed for ADAR1. To determine the specific role of RNA editing by ADAR1, we generated mice with an editing-deficient knock-in mutation (Adar1(E861A), where E861A denotes Glu(861)->Ala(861)). Adar1(E861A/E861A) embryos died at ~E13.5 (embryonic day 13.5), with activated interferon and double-stranded RNA (dsRNA)-sensing pathways. Genome-wide analysis of the in vivo substrates of ADAR1 identified clustered hyperediting within long dsRNA stem loops within 3' untranslated regions of endogenous transcripts. Finally, embryonic death and phenotypes of Adar1(E861A/E861A) were rescued by concurrent deletion of the cytosolic sensor of dsRNA, MDA5. A-to-I editing of endogenous dsRNA is the essential function of ADAR1, preventing the activation of the cytosolic dsRNA response by endogenous transcripts. PMID- 26275110 TI - Effect of individual health education on hyperphosphatemia in the Hakkas residential area. AB - The Hakka are a sub-ethnicity with unique diet customs in South China. This study investigated hyperphosphatemia in hemodialysis patients in relation to the current Hakka dietary customs and explored health education patterns for hyperphosphatemia control. Two continuous cross-sectional surveys were conducted among the local patients on dialysis. After the first survey, the patients with hyperphosphatemia were semi-randomized into regular (group 1) and individual (group 2) education groups. Regular health education was conducted for both groups. In group 2, the awareness of health knowledge and dietary customs was investigated using a self-designed questionnaire. Based on the questionnaire, individual dietary guidance was given. The second survey was performed after 3 months. In the first survey, a high-phosphorus diet was found in all 46 patients with 43 (93.5%) diagnosed with hyperphosphatemia. In group 1 and group 2, 15 patients and 25 patients completed the two surveys, respectively. In group 1, no patient changed their dietary habits; however, in group 2, some patients did. The level of serum inorganic phosphorus in group 1 increased significantly. In group 2, the data remained stable; the awareness rate of chronic kidney disease-mineral and bone disorder (CKD-MBD) increased, and six patients with good compliance showed decreased serum inorganic phosphorus (p = 0.046). High-phosphorus dietary customs and low CKD-MBD knowledge awareness are important reasons for the difficulty in hyperphosphatemia control of patients on dialysis in the Hakka region. Individual health education led by medical staff might be helpful in hyperphosphatemia control, but the pattern still needs further exploration. PMID- 26275111 TI - Valvular calcification and left ventricular modifying in peritoneal dialysis patients. AB - BACKGROUND: Cardiac valve calcification (CVC) and left ventricular (LV) alterations are frequent complication in end-stage renal disease (ESRD). We determined the prevalence of CVC and LV hypertrophy (LVH) in ESRD patients before renal replacement therapy and 12 months after peritoneal dialysis (PD). METHODS: A prospective longitudinal of 50 incident PD patients was studied. Demographic and clinical data were recorded and blood assayed at baseline and after 1-year of follow-up. CVC and LVH were evaluated by M-mode two-dimensional echocardiography. RESULTS: CVC of the mitral and aortic valves and of both valves were noted in 30, 18 and 10% of patients, respectively. After 12 months of PD regimen, 20% patients had aortic, 24% mitral and 8% had calcification of both valves. After one year of PD, LVH was 62 and 36% in patients with and without CVC, respectively (p < 0.05). Endothelin-1 is an independent predictor of CVC at the baseline, while nitric oxide is inversely an independent predictor at the end of follow-up. CONCLUSIONS: CVC is associated with LVH in PD patients. These findings identified a potential role for monitored markers to be incorporated into therapeutic strategies aimed at detection and treatment of cardiovascular complications and prevention strategies. PMID- 26275112 TI - Protective effect of pomegranate seed oil against cisplatin-induced nephrotoxicity in rat. AB - PURPOSE: Clinical use of cisplatin is limited by its nephrotoxicity. Cisplatin induced nephrotoxicity is associated with an increase in oxidative stress, leading ultimately to kidney dysfunction. The aim of this study was to investigate the effect of pomegranate seed oil against nephrotoxicity induced by cisplatin in adult rats. METHODS: Animals were divided into four groups. Group I received corn oil (1 mL/kg). Group II received cisplatin (8 mg/kg). Group III and IV received pomegranate seed oil (PSO) 0.4 mL/kg and 0.8 mL/kg one hour before cisplatin injection for 3 days, respectively. Blood samples were collected by cardiac puncture and used for measuring urea and creatinine concentration. Twenty hour urine samples were collected to measure protein and glucose concentration. The right kidney fixed in formalin for histological examination and the left kidney was homogenized for measurement of malondialdehyde and total sulfhydryl groups. RESULTS: A significant elevation of serum creatinine, urea, urinary glucose, protein concentrations, and non-significant decrease in total thiol content and increase in MDA level in kidney homogenates were observed in cisplatin-treated rats. Also cisplatin reduced animal's body weight. Mild-to moderate tubular cell necrosis, hyaline casts, and vascular congestion were observed in group II. PSO pre-treatment significantly decreased urinary protein, glucose, and serum creatinine concentration. PSO also caused a decrease in serum urea, renal MDA, and increase in thiol content, but the level of these parameters were not significant. CONCLUSION: The present results suggest that PSO is an effective agent for the prevention of cisplatin-induced renal dysfunction and oxidative damage in rat. PMID- 26275114 TI - The long-term outlook to final outcome and steroid treatment results in children with idiopathic nephrotic syndrome. AB - Idiopathic Nephrotic Syndrome (INS) was defined as combination of a nephrotic syndrome and non-specific histological abnormalities of the kidney. Among these abnormalities, minimal change nephrotic syndrome (MCNS) is the most common. We report our experience with MCNS; its clinical course, treatments and outcomes. One-hundred twenty children (66 male, 54 female) with MCNS, admitted to Nephrology Department between 1987-2009 was assessed. Their clinical presentations, treatment and disease courses were reviewed. The mean duration of follow-up was 11.5 +/- 1.9 years. Initially, all patients given prednisone 2 mg/kg/ day single dose per four weeks a followed by eight weeks of the same daily dose given every other day. After week 12, prednisone was progressively tapered off at the rate of 0.5 mg/kg per 15 daily intervals until complete discontinuation had been achieved by week 16. Steroid resistance was accepted as no achievement of remission following four weeks of prednisone 2 mg/kg/day followed by three intravenous pulses of corticosteroids. At the end of the initial steroid treatment, 106 (88.3%) patients were determinate steroid responsive while 14 (11.7%) patients were steroid resistance. Thirty-eight patients underwent biopsy. At the end of study recovery rate was increased from 88.3% to 94.1%. In conclusion, most of patients entered remission by our therapy end of follow up time. With the support of our satisfactory results among the whole study group, long-term prednisolone treatment still remains valid. PMID- 26275115 TI - Cabin1 localizes in glomerular podocyte and undergoes nuclear translocation during podocyte injury. AB - CONTEXT: Podocyte injury is related to increasing proteinuria and contributes to the progression of kidney disease. Calcineurin binding protein 1 (Cabin1) is a repressor of myocyte enhancer factor 2 (MEF2) and calcineurin-mediated transcription in the immune system. Moreover, Cabin1 interacts with p53 and negatively regulates p53 in tumor cells. However, its function in kidney is unknown. OBJECTIVE: To explore the exact localization of Cabin1 in glomeruli, as well as the relationship between Cabin1 and podocyte injury. METHODS: Sprague Dawley rats were sacrificed to observe the localization and protein expression of Cabin1 in the kidney. Cabin1 localization and protein expression were detected by immunofluorescence staining and western blot, respectively. Mouse podocytes were cultivated at 33 degrees C to propagate, then cells were transferred to an incubator at 37 degrees C to allow differentiation. Differentiated podocytes were stimulated by angiotensin II (AngII) or AngII plus tacrolimus. Cells were harvested to detect the localization and protein expression of Cabin1. Cytoplasmic and nuclear protein were separated by protein extraction kit. RESULTS: Cabin1 mainly localized in the nuclei of glomerular innate cells, it colocalized with WT-1 in podocytes nuclei. Western bolt showed Cabin1 protein remarkably expressed in renal cortex. AngII-induced Cabin1 nuclear protein significantly increased, accompanied by cytoskeleton disruption in cultured mouse podocytes. CONCLUSION: Cabin1 localizes in glomerular podocytes. AngII induces nuclear translocation of Cabin1 in cultured podocytes. PMID- 26275116 TI - Protective effects of probiotic Lactobacillus plantarum BJ0021 on liver and kidney oxidative stress and apoptosis induced by endosulfan in pregnant rats. AB - Endosulfan (EDS) is one of the most widely organochlorine insecticide used in many parts of the world, although it is currently banned or severely restricted in use in some countries. EDS causes a variety of negative effects in non-target species including humans. Therefore, the aim of the present study was to investigate the possible protective effects of Lactobacillus plantarum BJ0021 on toxicity, oxidative stress, and apoptosis induced by EDS intoxication on liver and kidneys of pregnant rats. This pesticide induced a significant increase in total cholesterol, alanine-amino transferase (ALAT), aspartate-amino transferase (ASAT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), urea and creatinine in serum, while urinary urea and creatinine were lower than those of the control group. In the liver and kidney, lipid peroxidation increased significantly, the antioxidant levels, such as superoxide dismutase (SOD) and catalase (CAT) were markedly depressed and TdT-mediated dUTP-biotin Nick End Labeling (TUNEL) revealed more apoptotic cells. In contrast, co-administration of L. plantarum BJ0021 to EDS-treated animals ameliorated most of these biochemical parameters, but the activity of antioxidant enzymes (SOD, CAT) did not modify and the number of apoptotic nuclei remained significantly raised in kidney compared to control. In conclusion, the administration of L. plantarum BJ0021 decreased apoptosis and might play a protective role in reducing toxicity of EDS in pregnant rats. PMID- 26275117 TI - Effects of intradialytic exercise on systemic cytokine in patients with chronic kidney disease. AB - BACKGROUND: Immunological dysfunctions and a pro-inflammatory environment are associated with higher risk of cardiovascular diseases in chronic kidney disease (CKD). Physical exercise can be an important anti-inflammatory strategy, but the effects in CKD remain poorly investigated. OBJECTIVE: Evaluate the acute inflammatory response to intradialytic exercise in the peripheral blood of individuals with CKD. METHODS: Nine patients, of both genders, with CKD and allocated in the ambulatory of hemodialysis of Hospital Ernesto Dornelles (Brazil), performed two sessions of hemodialysis (HD) in random form: aerobic intradialytic exercise sessions (EX, 20 min of moderate exercise in cycle ergometer) and a control hemodialysis session (CON). Peripheral blood collection was made at the baseline, during and immediately after HD to evaluate the cytokine profile: interleukin-6, interleukin-10 (IL-10), interleukin-17a (IL 17a), interferon-gamma (INF-gamma) and tumoral necrosis factor-alpha (TNF-alpha). RESULTS: INF-gamma decreased during HD when compared with the pre moment in both sessions, while an increase in post HD was only found in the CON session. IL-17 was higher in post when compared with during HD in both sessions. In addition to the time effect, IL-10 presented a time * group interaction and the relative changes were significantly higher in EX when compared with the CON session. The relative changes in TNF-alpha tended to be higher in CON when compared with EX immediately post HD session. CONCLUSIONS: These data indicate that 20 min of intradialytic exercise have modest effect in systemic inflammation. However, the significant increase in IL-10 may indicate an immunoregulatory effect of physical exercise. PMID- 26275119 TI - Comparison of video laryngoscopy versus direct laryngoscopy during urgent endotracheal intubation; trial of the route of early nutritional support in critically ill adults; and transfusion of plasma, platelets, and red blood cells in a 1:1:1 versus a 1:1:2 ratio and mortality in patients with severe trauma. PMID- 26275118 TI - Immobilization of Firefly Luciferase on PVA-co-PE Nanofibers Membrane as Biosensor for Bioluminescent Detection of ATP. AB - The bioluminescent reaction catalyzed by firefly luciferase has become widely established as an outstanding analytical system for assay of adenosine triphosphate (ATP). When in solution, the luciferase is unstable and cannot be reused. The problem can be partially solved by immobilizing the luciferase on solid substrates. The poly(vinyl alcohol-co-ethylene) (PVA-co-PE) nanofibers membrane has abundant active hydroxyl groups on the surface. The PVA-co-PE nanofibers membrane was first activated by cyanuric chloride with triazinyl group. Then the activated PVA-co-PE nanofibers membrane was subsequently reacted with 1,3-propanediamine and biotin. The firefly luciferase was immobilized onto the surface of 1,3-propanediamine- and biotin-functionalized membranes. The surface chemical structure and morphologies of nanofibers membranes were characterized by FTIR-ATR spectra and SEM. The hydrophilicity of membranes was tested by water contact angle measurements. The detection of fluorescence intensity displayed that the firefly-luciferase-immobilized PVA-co-PE nanofibers membranes indicated high catalytic activity and efficiency. Especially, the firefly-luciferase-immobilized nanofiber membrane which was functionalized by biotin can be a promising candidate as biosensor for bioluminescent detection of ATP because of its high detection sensitivity. PMID- 26275120 TI - Development of chronic lymphocytic leukaemia during ipilimumab therapy in a patient with metastatic melanoma. PMID- 26275121 TI - The Placental Distal Villous Hypoplasia Pattern: Interobserver Agreement and Automated Fractal Dimension as an Objective Metric. AB - The distal villous hypoplasia (DVH) pattern is a placental correlate of fetal growth restriction. Because the pattern seems to involve less complexity than do appropriately developed placental villi, we postulated that it may be associated with lower fractal dimension-a mathematical measure of complexity. Our study objectives were to evaluate interobserver agreement related to the DVH pattern among expert pathologists and to determine whether pathologist classification of DVH correlates with fractal dimension. A study set of 30 images of placental parenchyma at *4 magnification was created by a single pathologist from a digital slide archive. The images were graded for the DVH pattern according to pre specified definitions and included 10 images graded as "no DVH" (grade = 0), 10 with mild to moderate DVH (grade = 1), and 10 with severe DVH (grade = 2). The images were randomly sorted and shown to a panel of 4 international experts who similarly graded the images for DVH. Weighted kappas were calculated. For each image, fractal dimension was calculated by the Box Counting method. The correlation coefficient between (1) the averaged DVH scores obtained by the 5 pathologists and (2) fractal dimension was calculated. The mean weighted kappa score among the observers was 0.59 (range: 0.42-0.70). The correlation coefficient between fractal dimension and the averaged DVH score was -0.915 (P < 0.001). Expert pathologists achieve fair to substantial agreement in grading DVH, indicating consensus on the definition of DVH. Distal villous hypoplasia correlates extremely well with fractal dimension and represents an objective measure for DVH. PMID- 26275123 TI - Effects of acetone, acetonitrile, ethanol, methanol and DMSO on cytochrome P450 in rainbow trout (Oncorhynchus mykiss) hepatic microsomes. AB - In vitro impacts of five organic solvents on cytochrome P450 (CYP450) enzyme activity were investigated using hepatic microsomes of rainbow trout. The rates of several CYP450-mediated reactions were investigated at solvent concentrations ranging from 0.01% to 3%. The solvents greatly affected all tested reactions. In at least 0.8% ethanol, 2% methanol or acetone, 1% acetonitrile or 3% dimethyl sulfoxide (DMSO), 7-ethoxyresorufin-O-deethylase (EROD) activity decreased and at 3% acetonitrile or ethanol, it was undetected. At 3%, all tested solvents except methanol reduced 7-benzyloxy-4-trifluoromethylcoumarin-O-debenzylase (BFCOD) activity, but at low concentrations of ethanol (2% and lower) or DMSO (1% and lower), it was induced. This was not seen with the inclusion of a pre-incubation step. p-Nitrophenolhydroxylase (PNPH) activity was not affected at concentrations below 1% DMSO, and at 2% acetonitrile it was reduced, as it was above 1% methanol or 0.5% ethanol. Acetone did not affect PNPH activity with or without a pre incubation step. In general, the degree of inhibition was similar with and without the pre-incubation step. We conclude that the concentration of organic solvent for solubilizing the substrate and inhibitor in in vitro microsomal studies should be minimized. PMID- 26275122 TI - HIV-infected men who have sex with men, before and after release from jail: the impact of age and race, results from a multi-site study. AB - The US HIV/AIDS epidemic is concentrated among men who have sex with men (MSM). Black men are disproportionately affected by incarceration and Black MSM experience higher infection rates and worse HIV-related health outcomes compared to non-Black MSM. We compared HIV treatment outcomes for Black MSM to other HIV infected men from one of the largest cohorts of HIV-infected jail detainees (N = 1270) transitioning to the community. Of the 574 HIV-infected men released, 113 (19.7%) self-identified as being MSM. Compared to other male subgroups, young Black MSM (<30 years old, N = 18) were significantly less likely: (1) before incarceration, to have insurance, access to an HIV healthcare provider, and use cocaine; (2) during incarceration, to receive a disease management intervention; and (3) in the 6 months post-release, to link to HIV care. Interventions that effectively link and retain young HIV-infected Black MSM in care in communities before incarceration and post-release from jail are urgently needed. PMID- 26275124 TI - Mitigation of opioid off-target effects and identification of structural drivers of opioid receptor engagement for BACE-1 small molecule inhibitors. AB - Application of safety lead optimization screening strategies during the early stage of drug discovery led to the identification of a series of CNS-active small molecule inhibitors with opioid off-target effects, as evidenced by potent agonistic activity in functional cell-based assays for mu (MOP), kappa (KOP) and delta (DOP) opioid receptors. The translation of these effects was confirmed in vivo with the following observations: hypoactivity and decreased fecal production in rats (characteristic of MOP agonism); increased urine production in rats (characteristic of KOP agonism); and decreased intestinal transit time in mice, which was partially blocked by the MOP antagonist naloxone, demonstrating that the in vivo effects were specific for MOP. Based on the confirmation of in vitro in vivo translatability, an in vitro screening strategy was implemented that resulted in the identification of an optimized backup molecule, devoid of in vivo off-target opioid effects. In addition, in silico modeling by docking of the various molecules to the opioid receptors allowed the identification of the structural drivers of these off-target effects, which can be applied to future chemical-design criteria. Thus, implementation of the safety lead optimization strategy described in this article demonstrates the utility and impact of such approaches on risk mitigation and identification of lead small molecules with improved safety profiles. PMID- 26275125 TI - Neuroprotective effect of carnosine and cyclosporine-A against inflammation, apoptosis, and oxidative brain damage after closed head injury in immature rats. AB - CONTEXT: Traumatic brain injury in the pediatric population can have a great economic and emotional impact on both the child's family and society. OBJECTIVE: The present study aimed to compare the effects of carnosine (CAR) and/or cyclosporine A (CyA) on oxidative brain damage after closed head injury (CHI) in immature rats. MATERIALS AND METHODS: Thirty-day-old rat pups were divided into five groups: non-traumatic control group, trauma group underwent CHI, trauma group injected with CAR (200 mg/kg, i.p.) following CHI for 7 d, trauma group injected with CyA (20 mg/kg, i.p.) given 15 min and 24 h after CHI, and trauma group treated with CAR and CyA. At the end of the treatment, rats were sacrificed; blood and brains were collected for assessing different biochemical parameters. RESULTS: Trauma significantly increased brain level of malondialdehyde, nitric oxide, glucose, calcium, inflammatory mediators. Brain DNA damage was confirmed by comet assay and the significant increase in brain caspase-3 activity. Moreover, the serum level of Fas ligand in traumatized animals was significantly elevated. Concomitant decrease in brain-reduced glutathione (GSH) and calcium-adenosine triphosphatase activity was observed in the traumatized-untreated group. Treatment of traumatized animals with CAR and/or CyA ameliorated all the biochemical changes induced by CHI with marked protective effect in the combination group. DISCUSSION AND CONCLUSION: CAR and CyA exerted a synergistic neuroprotective effect against CHI through blocking the induction of lipid peroxidation, reducing inflammatory, and oxidative stress biomarkers, preserving brain GSH content, and reducing the alterations in brain apoptotic biomarkers in traumatized animals. PMID- 26275126 TI - (68)Ga-DOTA-peptide: A novel molecular biomarker for nasopharyngeal carcinoma. AB - BACKGROUND: Increased somatostatin receptor (SSTR) expression in patients with undifferentiated nasopharyngeal carcinoma (NPC) has been demonstrated with receptor autoradiography, (111) In-Octreotide scintigraphy, and (68) Ga-DOTA-TOC positron emission tomography (PET)/CT imaging. We sought to compare and correlate the uptake of fluorodeoxyglucose (FDG) and DOTA-NOC in undifferentiated NPC to ascertain the possible role of (68) Ga-DOTA-NOC PET/CT as a new imaging biomarker and to assess whether targeted peptide receptor radionuclide therapy is a feasible treatment option. METHODS: After obtaining approval from our institutional review board, 4 patients with biopsy proven nonkeratinizing undifferentiated NPC who had just undergone routine staging/restaging (18) F-FDG PET/CT imaging were prospectively and consecutively recruited for (68) Ga-DOTA NOC PET/CT imaging. Of these 4 patients, 3 were newly diagnosed with untreated NPC, whereas 1 patient was diagnosed with a case of recurrent NPC with previous treatment. These patients subsequently underwent (68) Ga-DOTA-NOC PET/CT within 10 days from the (18) F-FDG PET/CT to ensure lesion comparability. Tracer uptake in tumor lesions were assessed visually and semiquantitatively by measuring maximum standardized uptake values (SUVmax). RESULTS: There were 12 FDG-avid lesions of which 7 showed avid uptake of DOTA-NOC greater than liver uptake, whereas 5 showed low uptake of DOTA-NOC less than liver uptake. Subset analysis of the FDG-avid lesions at the primary and recurrent sites showed that all the FDG-avid primary tumors in the nasopharynx showed avid uptake of DOTA-NOC. On the contrary, the case of recurrent NPC showed avid FDG uptake but low DOTA-NOC uptake. Subset analysis of the suspicious FDG-avid cervical lymph nodes showed that 50% of them demonstrated avid DOTA-NOC uptake greater than liver uptake, whereas the remaining demonstrated low-grade DOTA-NOC uptake less than liver uptake. The 2 subcentimeter cervical lymph nodes that showed low-grade uptake of FDG lower than mediastinal blood pool activity were deemed to be reactive/inflammatory and showed low-grade uptake of DOTA-NOC. CONCLUSION: This study highlights the potential of (68) Ga-DOTA-peptide PET/CT as a new molecular biomarker for newly diagnosed undifferentiated NPC, and less so for recurrent NPC and metastatic nodes. This potentially opens up new diagnostic and therapeutic options in the management of undifferentiated NPC. PMID- 26275127 TI - The structure of DSM-5 posttraumatic stress disorder symptoms in war veterans. AB - BACKGROUND AND OBJECTIVES: The present research examined the underlying factor structure of posttraumatic stress disorder (PTSD) as conceptualized in the recently published fifth edition of the Diagnostic and statistical manual of mental disorders (DSM-5). DESIGN: Participants were 258 trauma-exposed Iraq/Afghanistan war veterans. METHODS: A self-report measure of PTSD symptoms was administered to all participants and confirmatory factor analysis (CFA) was used to compare several different models of PTSD. RESULTS: CFA revealed that the best-fitting model was a six-factor model in which symptoms loaded onto the factors of intrusion, avoidance, negative affect, anhedonia, dysphoric arousal, and anxious arousal. CONCLUSIONS: These findings have important implications for ongoing conceptualization of PTSD and suggest that additional modifications to the diagnostic criteria for PTSD may still be warranted to more accurately reflect the underlying structure of PTSD symptoms. PMID- 26275130 TI - Author Response: Small Fiber Neuropathy and Wilson Disease. PMID- 26275129 TI - Small Fiber Neuropathy and Wilson Disease. PMID- 26275128 TI - Novel Nrf2/ARE activator, trans-Coniferylaldehyde, induces a HO-1-mediated defense mechanism through a dual p38alpha/MAPKAPK-2 and PK-N3 signaling pathway. AB - The induction of detoxifying enzymes and antioxidant proteins by chemopreventive agents protects cells from oxidizing substances capable of damaging DNA integrity and initiating carcinogenesis. Coniferyl aldehyde, a naturally occurring substance, has been found in many foods and edible plants. We and others previously demonstrated that trans-coniferylaldehyde (t-CA) has potential antimutagenic and antioxidant properties. However, the mechanism underlying its Nrf2-mediated antioxidant effect remains largely unknown. In the present study, we demonstrated that t-CA significantly stimulated antioxidant-responsive element (ARE)-driven luciferase activity in a cell model and increased the expression of ARE-dependent detoxifying/antioxidant genes and their protein products in vitro and in vivo. The detoxifying/antioxidant genes activated by t-CA, especially heme oxygenase-1 (HO-1), were found to be involved in its cytoprotective effects against oxidative stress and cell injuries elicited by carcinogens tert butylhydroperoxide and arecoline. Furthermore, the t-CA-induced phosphorylation and nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) played a crucial role in this ARE-mediated cellular defense. Moreover, we found that p38 MAPK and protein kinase C (PKC) signaling pathways participated in the t CA-induced, Nrf2-mediated cytoprotective effect. Among them, p38alpha/MAPKAPK-2 and an atypical PKC, PK-N3, were critical for the activation of the Nrf2/HO-1 axis by t-CA. In conclusion, we demonstrated for the first time that t-CA attenuates carcinogen-induced oxidative stress by activating Nrf2 via p38alpha/MAPKAPK-2- and PK-N3-dependent signaling pathways. In addition, t-CA increased the level of Nrf2-mediated detoxifying/antioxidant proteins in vivo, suggesting that t-CA may have potential for use in the management of carcinogenesis and meriting further investigation. PMID- 26275131 TI - Measurement of Ex Vivo Porcine Lens Shape During Simulated Accommodation, Before and After fs-Laser Treatment. AB - PURPOSE: According to Helmholtz, accommodation is based on the flexibility of the crystalline lens, which decreases with age, causing presbyopia. With femtosecond (fs)-lentotomy treatment, it is possible to restore the flexibility of presbyopic lenses. The efficiency of the treatment can be systematically evaluated using the finite element method based on experimental data. The purpose of this study was to quantify the shape change of ex vivo lenses in different accommodation states according to the fs-lentotomy treatment. METHODS: Five lenses with ciliary body excised from ex vivo porcine eyes (age: approximately 6 months, exact age unknown) were stretched in an accommodation device before and after laser treatment. Depending on the accommodation state, the lens shape, reconstructed from lens thickness, diameter, and anterior and posterior curvature, was measured using optical coherence tomography (OCT). The complete lens shape was parameterized and each measured parameter was compared to the results of a control group (n = 5, age: approximately 6 months, exact age unknown) without treatment. RESULTS: The amplitudes of the parameters thickness (+140%), diameter (+54%), and anterior radius of curvature (+57%) significantly increased after treatment (P < 0.05), and showed no significant change for the control group. By contrast, the amplitude of the posterior radius of curvature showed no change after treatment (P > 0.05). CONCLUSIONS: Measurement of the lens shape in different accommodation states was successful and showed significant changes after the treatment. The resulting data will be utilized as input for a finite element model to systematically evaluate the effect of fs-lentotomy treatment in future work. PMID- 26275132 TI - CD1 Mouse Retina Is Shielded From Iron Overload Caused by a High Iron Diet. AB - PURPOSE: High RPE iron levels have been associated with age-related macular degeneration. Mutation of the ferroxidase ceruloplasmin leads to RPE iron accumulation and degeneration in patients with aceruloplasminemia; mice lacking ceruloplasmin and its homolog hephaestin have a similar RPE degeneration. To determine whether a high iron diet (HID) could cause RPE iron accumulation, possibly contributing to RPE oxidative stress in AMD, we tested the effect of dietary iron on mouse RPE iron. METHODS: Male CD1 strain mice were fed either a standard iron diet (SID) or the same diet with extra iron added (HID) for either 3 months or 10 months. Mice were analyzed with immunofluorescence and Perls' histochemical iron stain to assess iron levels. Levels of ferritin, transferrin receptor, and oxidative stress gene mRNAs were measured by quantitative PCR (qPCR) in neural retina (NR) and isolated RPE. Morphology was assessed in plastic sections. RESULTS: Ferritin immunoreactivity demonstrated a modest increase in the RPE in 10-month HID mice. Analysis by qPCR showed changes in mRNA levels of iron-responsive genes, indicating moderately increased iron in the RPE of 10 month HID mice. However, even by age 18 months, there was no Perls' signal in the retina or RPE and no retinal degeneration. CONCLUSIONS: These findings indicate that iron absorbed from the diet can modestly increase the level of iron deposition in the wild-type mouse RPE without causing RPE or retinal degeneration. This suggests regulation of retinal iron uptake at the blood retinal barriers. PMID- 26275133 TI - The Contribution of Genetic Architecture to the 10-Year Incidence of Age-Related Macular Degeneration in the Fellow Eye. AB - PURPOSE: To correlate a genetic risk score based on age-related macular degeneration (AMD) susceptibility genes with the risk of AMD in the second eye. METHODS: This is a retrospective, open cohort study consisting of 891 unilateral AMD patients, who were followed for at least 12 months and recruited from three institutes. DNAs were genotyped using Illumina OmniExpress, HumanOmni2.5-8, and/or HumanExome. Survival analyses and Cox proportional hazard models were used to examine the association between 11 AMD susceptibility genes and the duration until second-eye involvement in 499 samples from Kyoto University, which were replicated in two other cohorts. Genetic risk score (GRS) was also evaluated. RESULTS: The ARMS2 rs10490924 recessive model (hazard ratio [HR]meta = 2.04; Pmeta = 3.4 * 10-3) and CFH rs800292 additive model (HRmeta = 1.77; Pmeta = 0.013) revealed significant associations with second-eye involvement. The dominant model of TNFRSF10A rs13278062, VEGFA rs943080, and CFI rs4698775 showed consistent effects across three datasets (I2 = 0%; HRmeta = 1.46, 1.30, 1.51, respectively). The GRS using these five single nucleotide polymorphisms (SNPs) was also significantly associated (HRmeta [per score] = 2.42; P = 2.2 * 10-5; I2 = 0%). After 10 years from the first visit, the patients within the top 10% by GRS showed a 51% hazard rate, in contrast to 2.3% among patients within the lowest 10% by GRS. CONCLUSIONS: We demonstrated that the GRS using ARMS2, CFH, TNFRSF10A, VEGFA, and CFI was significantly associated with second-eye involvement. Genetic risk has high predictive ability for second-eye involvement of AMD. PMID- 26275134 TI - Mechanisms of Vertical Fusional Vergence in Patients With "Congenital Superior Oblique Paresis" Investigated With an Eye-Tracking Haploscope. AB - PURPOSE: To determine the mechanisms of vertical fusional vergence in patients with "congenital unilateral superior oblique paresis" (SOP) and to discuss the implications of these mechanisms. METHODS: Eleven patients were examined with our eye-tracking haploscope. RESULTS: Three different fusion mechanisms were found, producing significantly different cyclovergence to vertical vergence ratios (P < 0.05): primary use of the vertical rectus muscles in seven patients (ratio: 0.36 +/- 1.6), primary use of the oblique muscles in one patient (0.04), and use of the superior oblique muscle in the higher eye and the superior rectus muscle in the lower eye in three patients (1.15 +/- 0.32). Lancaster red-green testing showed alignment differences among these groups, primarily differences in amount of subjective extorsion between the two eyes in straight-ahead gaze: The patient with oblique-muscle-mediated fusion showed essentially no subjective extorsion (0.5 degrees ), the patients with vertical-rectus-muscle-mediated vertical fusion showed a mean +/- SD subjective extorsion of 3.6 degrees +/- 1.4 degrees , and the patients with the mixed (oblique/rectus) fusion mechanism showed 7.0 degrees +/- 1.7 degrees (P < 0.05). CONCLUSIONS: The choice of fusion mechanism may be a function of how much intorting effect is needed. Use of the oblique muscles bilaterally causes the least intorting effect, use of the vertical rectus muscles bilaterally adds more intorting effect, and activation of the "paretic" superior oblique muscle in the higher eye and the superior rectus muscle in the lower eye provides the greatest intorting effect. Subclassifying "congenital SOP" in this way (in which the "paretic" muscle may remain functional in many cases) may help guide its optimal surgical correction. PMID- 26275135 TI - Convergence and Accommodation Development Is Preprogrammed in Premature Infants. AB - PURPOSE: This study investigated whether vergence and accommodation development in preterm infants is preprogrammed or is driven by experience. METHODS: Thirty two healthy infants, born at mean 34 weeks gestation (range, 31.2-36 weeks), were compared with 45 healthy full-term infants (mean 40.0 weeks) over a 6-month period, starting at 4 to 6 weeks postnatally. Simultaneous accommodation and convergence to a detailed target were measured using a Plusoptix PowerRefII infrared photorefractor as a target moved between 0.33 and 2 m. Stimulus/response gains and responses at 0.33 and 2 m were compared by both corrected (gestational) age and chronological (postnatal) age. RESULTS: When compared by their corrected age, preterm and full-term infants showed few significant differences in vergence and accommodation responses after 6 to 7 weeks of age. However, when compared by chronological age, preterm infants' responses were more variable, with significantly reduced vergence gains, reduced vergence response at 0.33 m, reduced accommodation gain, and increased accommodation at 2 m compared to full term infants between 8 and 13 weeks after birth. CONCLUSIONS: When matched by corrected age, vergence and accommodation in preterm infants show few differences from full-term infants' responses. Maturation appears preprogrammed and is not advanced by visual experience. Longer periods of immature visual responses might leave preterm infants more at risk of development of oculomotor deficits such as strabismus. PMID- 26275136 TI - Design and Pharmacokinetic Characterization of Novel Antibody Formats for Ocular Therapeutics. AB - PURPOSE: To design and select the next generation of ocular therapeutics, we performed a comprehensive ocular and systemic pharmacokinetic (PK) analysis of a variety of antibodies and antibody fragments, including a novel-designed bispecific antibody. METHODS: Molecules were administrated via intravitreal (IVT) or intravenous (IV) injections in rabbits, and antibody concentrations in each tissue were determined by ELISA. A novel mathematical model was developed to quantitate the structure-PK relationship. RESULTS: After IVT injection, differences in vitreal half-life observed across all molecules ranged between 3.2 and 5.2 days. Modification or elimination of the fragment crystallizable (Fc) region reduced serum half-life from 9 days for the IgG to 5 days for the neonatal Fc receptor (FcRn) null mAb, to 3.1 to 3.4 days for the other formats. The F(ab')2 was the optimal format for ocular therapeutics with comparable vitreal half-life to full-length antibodies, but with minimized systemic exposure. Concomitantly, the consistency among mathematical model predictions and observed data validated the model for future PK predictions. In addition, we showed a novel design to develop bispecific antibodies, here with activity targeting multiple angiogenesis pathways. CONCLUSIONS: We demonstrated that protein molecular weight and Fc region do not play a critical role in ocular PK, as they do systemically. Moreover, the mathematical model supports the selection of the "ideal therapeutic" by predicting ocular and systemic PK of any antibody format for any dose regimen. These findings have important implications for the design and selection of ocular therapeutics according to treatment needs, such as maximizing ocular half-life and minimizing systemic exposure. PMID- 26275137 TI - Exposure to Atomic Bomb Radiation and Age-Related Macular Degeneration in Later Life: The Hiroshima-Nagasaki Atomic Bomb Survivor Study. AB - PURPOSE: To investigate the association between radiation exposure from the atomic bombings and the prevalence of age-related macular degeneration (AMD) among older residents of Hiroshima and Nagasaki. METHODS: The Adult Health Study is a cohort study of atomic bomb survivors living in Hiroshima and Nagasaki, comprising 2153 participants who underwent examinations with retinal fundus photographs in 2006-2008. The radiation dose to the eye for the analysis was estimated with the revised dosimetry system (DS02). The retinal photographs were graded according to the Wisconsin Age-Related Maculopathy Grading System modified for nonstereoscopic retinal images. Early and late AMD were defined according to the type of lesion detected in the worse eye of the participants. Person-specific data were analyzed by using a logistic regression model to assess the association between radiation dose and AMD. RESULTS: Among the 1824 subjects with gradable retinal images (84.7% of the overall participants), the estimated eye dose was widely distributed, with a mean of 0.45 Gy and standard deviation of 0.74 Gy. The prevalence of early and late AMD was 10.5% and 0.3%, respectively. There were no significant associations between radiation dose and AMD, with each 1-Gy increase in exposure, adjusted odds ratio was 0.93 (95% confidence interval [CI], 0.75 1.15) for early AMD and 0.79 (95% CI, 0.21-2.94) for late AMD. CONCLUSIONS: No significant associations were found between atomic bomb irradiation early in life and the prevalence of early or late AMD later in life among Japanese atomic bomb survivors. PMID- 26275138 TI - (Bis(terpyridine))copper(II) Tetraphenylborate: A Complex Example for the Jahn Teller Effect. AB - The surprisingly complicated crystal structure of (bis(terpyridine))copper(II) tetraphenylborate [Cu(tpy)2](BPh4)2 (tpy = 2,2':6',2"-terpyridine) consists of six crystallographically independent [Cu(tpy)2](2+) complexes. At ambient temperature, five out of six [Cu(II)N6] chromophores appear to be compressed octahedra, while at 100 K, four exhibit elongated and only two compressed octahedral geometry. Temperature dependent single crystal UV/vis (100, 298 K) and EPR measurements (20, 100, 298 K) as well as AOM calculations suggest that the octahedra which show apparently compressed octahedral geometry (XRD) result from dynamic Jahn-Teller behavior of elongated octahedra [Cu(II)N6]. The detailed correlation of structural and spectroscopic data allows an understanding of the strongly solvent-dependent structures of the [Cu(tpy)2](2+) complex in solution. PMID- 26275139 TI - Associations of Quality of Life with Service Satisfaction in Psychotic Patients: A Meta-Analysis. AB - BACKGROUND: Quality of life (QoL) has gained increasing attention as a desired outcome of psychosocial treatments targeting psychotic patients. Yet, the relationship between the patients' satisfaction with services and QoL has not been clearly established, perhaps due to the multidimensionality of the QoL concept and the variability in its assessment. AIM: This is the first systematic meta-analysis of all available evidence assessing the relationship between QoL and service satisfaction. METHODS: In all, 19 studies reporting data of 21 independent samples (N = 5,337) were included in the present meta-analysis. In moderator analyses, effects of age, sex, diagnoses (schizophrenia vs. other psychoses), treatment context (inpatients vs. outpatients), study design (cross sectional vs. longitudinal), and QoL domain (subjective vs. health-related) were examined. RESULTS: Analyses revealed a highly significant medium-sized effect (r = .30, p < .001) for the associations of QoL and service satisfaction. Effect sizes were significantly stronger for subjective than health-related quality of life (r = .35 vs. r = .14, respectively). Moreover, associations with subjective QoL remained largely robust when accounting for moderating variables, although there was a trend of stronger associations for outpatients compared to inpatients. In contrast, effect sizes for health-related QoL were small and only observable for samples with longitudinal designs. CONCLUSION: Associations between QoL and service satisfaction appear to be robust but are differentiated in regard to QoL domain. Our findings suggest that agents responsible for service design and implementation need to take the patients' perception of the service adequacy for achieving QoL enhancement into account. PMID- 26275140 TI - Blocking Dopaminergic Signaling Soon after Learning Impairs Memory Consolidation in Guinea Pigs. AB - Formation of episodic memories (i.e. remembered experiences) requires a process called consolidation which involves communication between the neocortex and hippocampus. However, the neuromodulatory mechanisms underlying this neocortico hippocampal communication are poorly understood. Here, we examined the involvement of dopamine D1 receptors (D1R) and D2 receptors (D2R) mediated signaling on memory consolidation using the Novel Object Recognition (NOR) test. We conducted the tests in male Hartley guinea pigs and cognitive behaviors were assessed in customized Phenotyper home cages utilizing Ethovision XT software from Noldus enabled for the 3-point detection system (nose, center of the body, and rear). We found that acute intraperitoneal injections of either 0.25 mg/kg SCH23390 to block D1Rs or 1.0 mg/kg sulpiride to block D2Rs soon after acquisition (which involved familiarization to two similar objects) attenuated subsequent discrimination for novel objects when tested after 5-hours in the NOR test. By contrast guinea pigs treated with saline showed robust discrimination for novel objects indicating normal operational processes undergirding memory consolidation. The data suggests that involvement of dopaminergic signaling is a key post-acquisition factor in modulating memory consolidation in guinea pigs. PMID- 26275141 TI - Cold Atmospheric Plasma Induces a Predominantly Necrotic Cell Death via the Microenvironment. AB - INTRODUCTION: Cold plasma is a partially ionized gas generated by an electric field at atmospheric pressure that was initially used in medicine for decontamination and sterilization of inert surfaces. There is currently growing interest in using cold plasma for more direct medical applications, mainly due to the possibility of tuning it to obtain selective biological effects in absence of toxicity for surrounding normal tissues,. While the therapeutic potential of cold plasma in chronic wound, blood coagulation, and cancer treatment is beginning to be documented, information on plasma/cell interaction is so far limited and controversial. METHODS AND RESULTS: Using normal primary human fibroblast cultures isolated from oral tissue, we sought to decipher the effects on cell behavior of a proprietary cold plasma device generating guided ionization waves carried by helium. In this model, cold plasma treatment induces a predominantly necrotic cell death. Interestingly, death is not triggered by a direct interaction of the cold plasma with cells, but rather via a transient modification in the microenvironment. We show that modification of the microenvironment redox status suppresses treatment toxicity and protects cells from death. Moreover, necrosis is not accidental and seems to be an active response to an environmental cue, as its execution can be inhibited to rescue cells. CONCLUSION: These observations will need to be taken into account when studying in vitro plasma/cell interaction and may have implications for the design and future evaluation of the efficacy and safety of this new treatment strategy. PMID- 26275142 TI - A Mouse Model for Imprinting of the Human Retinoblastoma Gene. AB - The human RB1 gene is imprinted due to integration of the PPP1R26P1 pseudogene into intron 2. PPP1R26P1 harbors the gametic differentially methylated region of the RB1 gene, CpG85, which is methylated in the female germ line. The paternally unmethylated CpG85 acts as promoter for the alternative transcript 2B of RB1, which interferes with expression of full-length RB1 in cis. In mice, PPP1R26P1 is not present in the Rb1 gene and Rb1 is not imprinted. Assuming that the mechanisms responsible for genomic imprinting are conserved, we investigated if imprinting of mouse Rb1 can be induced by transferring human PPP1R26P1 into mouse Rb1. We generated humanized Rb1_PPP1R26P1 knock-in mice that pass human PPP1R26P1 through the mouse germ line. We found that the function of unmethylated CpG85 as promoter for an alternative Rb1 transcript and as cis-repressor of the main Rb1 transcript is maintained in mouse tissues. However, CpG85 is not recognized as a gametic differentially methylated region in the mouse germ line. DNA methylation at CpG85 is acquired only in tissues of neuroectodermal origin, independent of parental transmission of PPP1R26P1. Absence of CpG85 methylation in oocytes and sperm implies a failure of imprint methylation establishment in the germ line. Our results indicate that site-specific integration of a proven human gametic differentially methylated region is not sufficient for acquisition of DNA methylation in the mouse germ line, even if promoter function of the element is maintained. This suggests a considerable dependency of DNA methylation induction on the surrounding sequence. However, our model is suited to determine the cellular function of the alternative Rb1 transcript. PMID- 26275143 TI - Effect of Acrylamide on Oocyte Nuclear Maturation and Cumulus Cells Apoptosis in Mouse In Vitro. AB - Acrylamide (ACR) is a chemical compound with severe neurotoxicity, genotoxicity, carcinogenicity and reproductive toxicity. Recent studies showed that ACR impairs the function of reproductive organs, e.g., epididymis and testes. In vitro maturation of mouse oocyte is a sensitive assay to identify potential chemical hazard to female fertility. The aim of this study was to evaluate the adverse effects of ACR on the nuclear maturation and cumulus cells apoptosis of mouse oocytes in vitro. Cumulus-oocyte complexes were incubated in a maturation medium containing 0, 5, 10 and 20 MUM of ACR. Chromosome alignment and spindle morphology of oocytes was determined by immunofluorescence and confocal microscopy. Our results showed that oocytes exposed to different doses of ACR in vitro were associated with a significant decrease of oocyte maturation, significant increase of chromosome misalignment rate, occurrence of abnormal spindle configurations, and the inhibition of oocyte parthenogenetic activation. Furthermore, apoptosis of cumulus cells was determined by TUNEL and CASPASE-3 assay. Results showed that apoptosis in cumulus cells was enhanced and the expression of CASPASE-3 was increased after cumulus-oocyte complexes were exposed to ACR. Therefore, ACR may affect the nuclear maturation of oocytes via the apoptosis of cumulus cells in vitro. PMID- 26275145 TI - Interplay between Aggregation and Coalescence of Polymeric Particles: Experimental and Modeling Insights. AB - In the present work, the aggregation behavior of polymeric particles possessing different glass transition temperatures (i.e., different "softnesses") has been studied to shed light on the interplay between aggregation and coalescence. In particular, the time evolution of the clusters hydrodynamic and gyration radii as well as of their structure factor has been monitored. With the help of an ad hoc developed deterministic model, based on population balance equations, it was possible to establish a link between the experimentally obtained light scattering data and the predicted particle size distribution. The simplicity of the model, involving one single adjustable parameter based on the coalescence characteristic time, allowed us to obtain a good accordance between simulations and experimental results with little computational effort. PMID- 26275144 TI - Cytoprotective Effects of Lysophospholipids from Sea Cucumber Holothuria atra. AB - Lysophospholipids are important signaling molecules in animals and metazoan cells. They are widely distributed among marine invertebrates, where their physiological roles are unknown. Sea cucumbers produce unique lysophospholipids. In this study, two lysophospholipids were detected in Holothuria atra for the first time, lyso-platelet activating factor and lysophosphatidylcholine, with nuclear magnetic resonance and liquid chromatography-time-of-flight mass spectrometric analyses. The lipid fraction of H. atra contained lyso-platelet activating factor and lysophosphatidylcholine, and inhibited H2O2-induced apoptosis in the macrophage cell line J774A.1. The antioxidant activity of the lysophospholipid-containing lipid fraction of H. atra was confirmed with the oxygen radical absorbance capacity method. Our results suggest that the lysophospholipids from H. atra are potential therapeutic agents for the inflammation induced by oxidative stress. PMID- 26275146 TI - Meteorologically Driven Simulations of Dengue Epidemics in San Juan, PR. AB - Meteorological factors influence dengue virus ecology by modulating vector mosquito population dynamics, viral replication, and transmission. Dynamic modeling techniques can be used to examine how interactions among meteorological variables, vectors and the dengue virus influence transmission. We developed a dengue fever simulation model by coupling a dynamic simulation model for Aedes aegypti, the primary mosquito vector for dengue, with a basic epidemiological Susceptible-Exposed-Infectious-Recovered (SEIR) model. Employing a Monte Carlo approach, we simulated dengue transmission during the period of 2010-2013 in San Juan, PR, where dengue fever is endemic. The results of 9600 simulations using varied model parameters were evaluated by statistical comparison (r2) with surveillance data of dengue cases reported to the Centers for Disease Control and Prevention. To identify the most influential parameters associated with dengue virus transmission for each period the top 1% of best-fit model simulations were retained and compared. Using the top simulations, dengue cases were simulated well for 2010 (r2 = 0.90, p = 0.03), 2011 (r2 = 0.83, p = 0.05), and 2012 (r2 = 0.94, p = 0.01); however, simulations were weaker for 2013 (r2 = 0.25, p = 0.25) and the entire four-year period (r2 = 0.44, p = 0.002). Analysis of parameter values from retained simulations revealed that rain dependent container habitats were more prevalent in best-fitting simulations during the wetter 2010 and 2011 years, while human managed (i.e. manually filled) container habitats were more prevalent in best-fitting simulations during the drier 2012 and 2013 years. The simulations further indicate that rainfall strongly modulates the timing of dengue (e.g., epidemics occurred earlier during rainy years) while temperature modulates the annual number of dengue fever cases. Our results suggest that meteorological factors have a time-variable influence on dengue transmission relative to other important environmental and human factors. PMID- 26275147 TI - Characterization of the Intestinal Lactobacilli Community following Galactooligosaccharides and Polydextrose Supplementation in the Neonatal Piglet. AB - Recently, prebiotic supplementation of infant formula has become common practice; however the impact on the intestinal microbiota has not been completely elucidated. In this study, neonatal piglets were randomized to: formula (FORM, n = 8), formula supplemented with 2 g/L each galactooligosaccharides (GOS) and polydextrose (PDX, F+GP, n = 9) or a sow-reared (SOW, n = 12) reference group for 19 days. The ileal (IL) and ascending colon (AC) microbiota were characterized using culture-dependent and -independent methods. 16S amplicon sequencing identified no differences at the genera level in the IL. Interestingly, six genera in the AC were significantly different between FORM and F+GP (P<0.05): Lactobacillus, Ruminococcus, Parabacteroides, Oscillospira, Hydrogenoanaerobacterium and Catabacter. In particular, the relative abundance of AC Lactobacillus was higher (P = 0.04) in F+GP as compared to FORM. Culture dependent analysis of the IL and AC lactobacilli communities of FORM and F+GP revealed a Lactobacillus spp. composition similar to 16S amplicon sequencing. Additional analysis demonstrated individual Lactobacillus isolates were unable to ferment PDX. Conversely, a majority of lactobacilli isolates could ferment GOS, regardless of piglet diet. In addition, the ability of lactobacilli isolates to ferment the longer chain GOS fragments (DP 3 or greater), which are expected to be present in the distal intestine, was not different between FORM and F+GP. In conclusion, prebiotic supplementation of formula impacted the AC microbiota; however, direct utilization of GOS or PDX does not lead to an increase in Lactobacillus spp. PMID- 26275149 TI - Correction: Ground-Vegetation Clutter Affects Phyllostomid Bat Assemblage Structure in Lowland Amazonian Forest. PMID- 26275148 TI - SHOEBOX Modulates Root Meristem Size in Rice through Dose-Dependent Effects of Gibberellins on Cell Elongation and Proliferation. AB - Little is known about how the size of meristem cells is regulated and whether it participates in the control of meristem size in plants. Here, we report our findings on shoebox (shb), a mild gibberellin (GA) deficient rice mutant that has a short root meristem size. Quantitative analysis of cortical cell length and number indicates that shb has shorter, rather than fewer, cells in the root meristem until around the fifth day after sowing, from which the number of cortical cells is also reduced. These defects can be either corrected by exogenous application of bioactive GA or induced in wild-type roots by a dose dependent inhibitory effect of paclobutrazol on GA biosynthesis, suggesting that GA deficiency is the primary cause of shb mutant phenotypes. SHB encodes an AP2/ERF transcription factor that directly activates transcription of the GA biosynthesis gene KS1. Thus, root meristem size in rice is modulated by SHB mediated GA biosynthesis that regulates the elongation and proliferation of meristem cells in a developmental stage-specific manner. PMID- 26275150 TI - Heme Signaling Impacts Global Gene Expression, Immunity and Dengue Virus Infectivity in Aedes aegypti. AB - Blood-feeding mosquitoes are exposed to high levels of heme, the product of hemoglobin degradation. Heme is a pro-oxidant that influences a variety of cellular processes. We performed a global analysis of heme-regulated Aedes aegypti (yellow fever mosquito) transcriptional changes to better understand influence on mosquito physiology at the molecular level. We observed an iron- and reactive oxygen species (ROS)-independent signaling induced by heme that comprised genes related to redox metabolism. By modulating the abundance of these transcripts, heme possibly acts as a danger signaling molecule. Furthermore, heme triggered critical changes in the expression of energy metabolism and immune response genes, altering the susceptibility towards bacteria and dengue virus. These findings seem to have implications on the adaptation of mosquitoes to hematophagy and consequently on their ability to transmit diseases. Altogether, these results may also contribute to the understanding of heme cell biology in eukaryotic cells. PMID- 26275151 TI - Trends and Determinants of Antiretroviral Therapy Patient Monitoring Practices in Kenya and Uganda. AB - INTRODUCTION: Patients receiving antiretroviral therapy (ART) require routine monitoring to track response to treatment and assess for treatment failure. This study aims to identify gaps in monitoring practices in Kenya and Uganda. METHODS: We conducted a systematic retrospective chart review of adults who initiated ART between 2007 and 2012. We assessed the availability of baseline measurements (CD4 count, weight, and WHO stage) and ongoing CD4 and weight monitoring according to national guidelines in place at the time. Mixed-effects logistic regression models were used to analyze facility and patient factors associated with meeting monitoring guidelines. RESULTS: From 2007 to 2012, at least 88% of patients per year in Uganda had a recorded weight at initiation, while in Kenya there was a notable increase from 69% to 90%. Patients with a documented baseline CD4 count increased from 69% to about 80% in both countries. In 2012, 83% and 86% of established patients received the recommended quarterly weight monitoring in Kenya and Uganda, respectively, while semiannual CD4 monitoring was less common (49% in Kenya and 38% in Uganda). Initiating at a more advanced WHO stage was associated with a lower odds of baseline CD4 testing. On-site CD4 analysis capacity was associated with increased odds of CD4 testing at baseline and in the future. DISCUSSION: Substantial gaps were noted in ongoing CD4 monitoring of patients on ART. Although guidelines have since changed, limited laboratory capacity is likely to remain a significant issue in monitoring patients on ART, with important implications for ensuring quality care. PMID- 26275152 TI - Allergen-Specific Immunotherapy with Monomeric Allergoid in a Mouse Model of Atopic Dermatitis. AB - Atopic dermatitis (AD) is a widespread and difficult to treat allergic skin disease and is a tough challenge for healthcare. In this study, we investigated whether allergen-specific immunotherapy (ASIT) with a monomeric allergoid obtained by succinylation of ovalbumin (sOVA) is effective in a mouse model of atopic dermatitis. An experimental model of AD was reproduced by epicutaneous sensitization with ovalbumin (OVA). ASIT was performed with subcutaneous (SC) administration of increasing doses of OVA or sOVA. The levels of anti-OVA antibodies, as well as cytokines, were detected by ELISA. Skin samples from patch areas were taken for histologic examination. ASIT with either OVA or sOVA resulted in a reduction of both the anti-OVA IgE level and the IgG1/IgG2a ratio. Moreover, ASIT with sOVA increased the IFN-gamma level in supernatants after splenocyte stimulation with OVA. Histologic analysis of skin samples from the sites of allergen application showed that ASIT improved the histologic picture by decreasing allergic inflammation in comparison with untreated mice. These data suggest that ASIT with a succinylated allergen represents promising approach for the treatment of AD. PMID- 26275155 TI - Gastrotomy Healing After Transgastric Peritoneoscopy: A Randomized Study in a Pig Model. AB - INTRODUCTION: Reliable closure and infection prevention are the main barriers for implementation of pure transgastric peritoneoscopy. The primary aim of this study was to assess healing of over the scope clip (OTSC) closed gastrotomies. MATERIALS AND METHODS: Pure transgastric peritoneoscopy was performed in 7 pigs. The pigs were randomized to 14 or 28 postoperative days (POD) of follow-up. Decontamination of the access route was performed before instrumentation. A full necropsy was performed. Closure was evaluated with histopathological examination of excised gastrorrhaphies. RESULTS: Three pigs were allowed 14 POD of follow-up, and 4 pigs were allowed 28 POD of follow-up. Survival was achieved in 6 of the 7 animals; 1 pig was euthanized due to diffuse peritonitis. Based on our definition, full-thickness healing had only been achieved in a single pig allowed 28 POD. With respect to clinical relevancy, full-thickness healing was deemed achieved in 4 of 6 pigs completing follow-up and in all pigs allowed and surviving 28 POD. Access required repeated punctures and the use of several endoscopic instruments. CONCLUSIONS: Full-thickness healing of the gastrotomy was only found in a single case when adhering to the per protocol definition. Endoscopic ultrasonography-guided access was difficult. It lacks reproducibility and needs refinement. Despite a combined decontamination regimen, infectious complications still occurred. PMID- 26275153 TI - Dopaminergic Toxin 1-Methyl-4-Phenylpyridinium, Proteins alpha-Synuclein and Glia Maturation Factor Activate Mast Cells and Release Inflammatory Mediators. AB - Parkinson's disease (PD) is characterized by the presence of Lewy bodies and degeneration of dopaminergic neurons. 1-methyl-4-phenylpyridinium (MPP+), a metabolite of neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and Lewy body component alpha-synuclein activates glia in PD pathogenesis. Mast cells and glia maturation factor (GMF) are implicated in neuroinflammatory conditions including Multiple Sclerosis. However, the role of mast cells in PD is not yet known. We have analyzed the effect of recombinant GMF, MPP+, alpha-synuclein and interleukin-33 (IL-33) on mouse bone marrow-derived cultured mast cells (BMMCs), human umbilical cord blood-derived cultured mast cells (hCBMCs) and mouse brain derived cultured astrocytes by quantifying cytokines/chemokines released using ELISA or by detecting the expression of co-stimulatory molecules CD40 and CD40L by flow cytometry. GMF significantly released chemokine (C-C motif) ligand 2 (CCL2) from BMMCs but its release was reduced in BMMCs from GMF knockout mice. GMF, alpha-synuclein and MPP+ released IL-1beta, beta-hexosaminidase from BMMCs, and IL-8 from hCBMCs. GMF released CCL5, and IL-33- induced the expression of GMF from hCBMCs. Novel GMF expression was detected in hCBMCs and BMMCs by immunocytochemistry. GMF released tumor necrosis factor-alpha (TNF-alpha) from mouse astrocytes, and this release was greater in BMMC- astrocyte coculture than in individual cultures. Flow cytometry results showed increased IL-33 expression by GMF and MPP+, and GMF-induced CD40 expression in astrocytes. Proinflammatory mediator release by GMF, MPP+ and alpha-synuclein, as well as GMF expression by mast cells indicate a potential therapeutic target for neurodegenerative diseases including PD. PMID- 26275156 TI - The Lived Experience of Patients Receiving Hemodialysis Treatment for End-Stage Renal Disease: A Qualitative Study. AB - BACKGROUND: End-stage renal disease (ESRD), the last stage of chronic kidney disease, is the point at which the kidneys are no longer able to support the body's needs. Thus, ESRD significantly impacts the day-to-day life of patients. To improve bodily functions and prolong life, patients with ESRD require renal replacement therapy in the form of either hemodialysis (HD) or kidney transplantation. Research has documented the impact of ESRD and HD on quality of life. There is a lack of qualitative studies that describe how ESRD sufferers in Thailand cope with daily life. PURPOSE: This study aimed to better understand the daily life experiences of Thai patients with ESRD who are on HD. METHODS: This study used a phenomenological approach and a semistructured interview guide. Thai men and women with ESRD and on HD were purposively recruited from an HD unit at one hospital in Thailand between February and May 2013. Inclusion criteria included (a) currently being treated for HD, (b) ability to communicate in Thai, and (c) age of over 18 years. Participants were asked to describe their problems, feelings, thoughts, and attitudes as well as how they experienced their lives. Data saturation was reached after the completion of 26 interviews. The data were analyzed using thematic analysis. RESULTS: The following themes emerged from the data: (a) facing life's limitations, (b) living with uncertainty, and (c) dependence on medical technology. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The authors hope that the findings increase the understanding of healthcare providers about the lived experience of Thai patients with ESRD on HD. Greater understanding is critical in helping healthcare providers identify the changes in practice that will be necessary to better care for and integrate the best holistic practices into standardized care for this population. PMID- 26275154 TI - Estimating the success of enzyme bioprospecting through metagenomics: current status and future trends. AB - Recent reports have suggested that the establishment of industrially relevant enzyme collections from environmental genomes has become a routine procedure. Across the studies assessed, a mean number of approximately 44 active clones were obtained in an average size of approximately 53,000 clones tested using naive screening protocols. This number could be significantly increased in shorter times when novel metagenome enzyme sequences obtained by direct sequencing are selected and subjected to high-throughput expression for subsequent production and characterization. The pre-screening of clone libraries by naive screens followed by the pyrosequencing of the inserts allowed for a 106-fold increase in the success rate of identifying genes encoding enzymes of interest. However, a much longer time, usually on the order of years, is needed from the time of enzyme identification to the establishment of an industrial process. If the hit frequency for the identification of enzymes performing at high turnover rates under real application conditions could be increased while still covering a high natural diversity, the very expensive and time-consuming enzyme optimization phase would likely be significantly shortened. At this point, it is important to review the current knowledge about the success of fine-tuned naive- and sequence based screening protocols for enzyme selection and to describe the environments worldwide that have already been subjected to enzyme screen programmes through metagenomic tools. Here, we provide such estimations and suggest the current challenges and future actions needed before environmental enzymes can be successfully introduced into the market. PMID- 26275157 TI - SIV-infection-driven changes of pattern recognition receptor expression in mesenteric lymph nodes and gut microbiota dysbiosis. AB - BACKGROUND: The impact of HIV infection on pattern recognition receptor (PRR) expression in gut-associated lymphoid tissue and its association with dysbiosis is not well understood. METHODS: PRR and cytokine gene expression were examined in mesenteric lymph nodes (mLN) of rhesus macaques during acute and chronic (untreated and early antiretroviral (ART) treated) infections. Gene expression was correlated with microbial abundance in the gut and immune activation. RESULTS: PRR expression rapidly increases during acute infection and is significantly decreased in chronic infection. Early ART maintains elevated PRR expression. Correlation analysis revealed three distinct groups of bacterial taxa that were associated with gene expression changes in infection. CONCLUSIONS: PRR and cytokine gene expression in the gut-draining mLN are rapidly modulated in response to viral infection and are correlated with gut dysbiosis. These data suggest that the dysregulation of PRR and related cytokine expression may contribute to chronic immune activation in SIV infection. PMID- 26275158 TI - Fibronectin binding protein and Ca2+ play an access key role to mediate pathogenesis in Mycobacterium tuberculosis: An overview. AB - The anomalous distribution of adhesive proteins throughout on the cell surface of the Mycobacterium tuberculosis H37 Rv and their contribution in cell surface adhesion and host-pathogen interaction remain elusive. The completion of M. tuberculosis H37 Rv genome sequence analysis gives some interesting information about polymorphic GC-rich repetitive sequence (PGRS) subfamily of M. tuberculosis that encodes fibronectin binding proteins (FnBP), which have been extensively studied, but the function in the pathogenesis of most of these proteins remains unknown and unclear. This review addresses the M. tuberculosis entry mechanism in the host cell. In particular, an effort has been made to focus on several aspects, (a) association of FnBP encodes by PE_PGRS protein family of M. tuberculosis during host-pathogen interactions. (b) Effect of calcium ions in and outside of the host cell is overriding to maintenance of calcium trafficking in phagocytosis. Furthermore, FnBP may be a potential source of antigenic variation that participating in evoking immune response. M. tuberculosis entry mechanism does not have a major influence alone, involvement of calcium ions, perhaps shed light on host-pathogen interaction relationship, and could open up new avenues for development of novel drug by targeting M. tuberculosis FnBP and blockade of selective adhesions could be useful for therapeutics. PMID- 26275159 TI - Comparative ultrastructure of CRM1-Nucleolar bodies (CNoBs), Intranucleolar bodies (INBs) and hybrid PML/p62 bodies uncovers new facets of nuclear body dynamic and diversity. AB - In order to gain insights on the nuclear organization in mammalian cells, we characterized ultrastructurally nuclear bodies (NBs) previously described as fluorescent foci. Using high resolution immunoelectron microscopy (I-EM), we provide evidence that CNoBs (CRM1-Nucleolar bodies) and INBs (Intranucleolar bodies) are distinct genuine nucleolar structures in untreated HeLa cells. INBs are fibrillar and concentrate the post-translational modifiers SUMO1 and SUMO-2/3 as strongly as PML bodies. In contrast, the smallest CRM1-labeled CNoBs are vitreous, preferentially located at the periphery of the nucleolus and, intricately linked to the chromatin network. Upon blockage of the CRM1-dependent nuclear export by leptomycin B (LMB), CNoBs disappear while p62/SQSTM1-containing fibrillar nuclear bodies are induced. These p62 bodies are enriched in ubiquitinated proteins. They progressively associate with PML bodies to form hybrid bodies of which PML decorates the periphery while p62/SQSTM1 is centrally located. Our study is expanding the repertoire of nuclear bodies; revealing a previously unrecognized composite nucleolar landscape and a new mode of interactions between ubiquitous (PML) and stress-induced (p62) nuclear bodies, resulting in the formation of hybrid bodies. PMID- 26275160 TI - The Effects of Compensatory Scanning Training on Mobility in Patients with Homonymous Visual Field Defects: A Randomized Controlled Trial. AB - INTRODUCTION: Homonymous visual field defects (HVFD) are a common consequence of postchiasmatic acquired brain injury and often lead to mobility-related difficulties. Different types of compensatory scanning training have been developed, aimed at decreasing consequences of the HVFD by changing visual scanning. AIM: The aim of the present study is to examine the effects of a compensatory scanning training program using horizontal scanning on mobility related activities and participation in daily life. METHOD: The main interest of this study is to assess the effectiveness of training on mobility-related activities and participation in daily life. Visual scanning tests, such as dot counting and visual search, and control measures for visual functions and reading have been included as well. First, it is examined how performance on scanning and mobility-related measures is affected in patients with HVFD by comparing scores with scores of a healthy control group (n = 25). Second, the effect of training is assessed using an RCT design, in which performance of 26 patients before and after training is compared to performance of 23 patients in a waiting list control group. RESULTS: Self-reported improvements after training were found, accompanied by improvements in detecting peripheral stimuli and avoiding obstacles during walking, especially in dual task situations in which a second task limits the attentional capacity available for compensatory scanning. Training only improved mobility-related activities in which detection of peripheral stimuli is important, while no improvement was found on tests that require other visual skills, such as reading, visual counting and visual search. CONCLUSION: This is the first RCT to evaluate the effects of a compensatory scanning training that is based on a systematic horizontal scanning rhythm. This training improved mobility-related activities. The results suggest that different types of compensatory scanning strategies are appropriate for different types of activities. TRIAL REGISTRATION: ISRCTN Registry ISRCTN16833414. PMID- 26275161 TI - Detection of human cytomegalovirus (CMV) DNA in feces has limited value in predicting CMV enteritis in patients with intestinal graft-versus-host disease after allogeneic stem cell transplantation. AB - BACKGROUND: Cytomegalovirus (CMV) enteritis after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is difficult to diagnose. We aimed to evaluate the sensitivity and specificity of the detection of CMV DNA in feces for predicting CMV enteritis. METHODS: HSCT patients with intestinal graft-versus host disease (GVHD) were enrolled if they met the following criteria: (i) underwent a colonoscopy and (ii) peripheral blood and feces specimens were available for CMV DNA detection within 24 h of colonoscopy. The colonoscopy histology was used as the gold standard for diagnosing CMV enteritis. RESULTS: Fifty-six patients underwent 58 colonoscopy examinations, and 7 were diagnosed as having CMV enteritis. Within 24 h of colonoscopy, 9 patients had detectable CMV in the feces and 19 patients had detectable CMV in the plasma, respectively. In the 7 patients with CMV enteritis, only 2 had detectable CMV in the stool, resulting in a sensitivity of 28.6%. In the 51 patients without CMV enteritis, 44 had no detectable CMV in the stool, with a specificity of 86.3%. CONCLUSION: We concluded that CMV detection in the feces was not a good predictor of CMV enteritis in patients with intestinal GVHD after allo-HSCT. PMID- 26275163 TI - Renal ultrasound and DMSA screening for high-grade vesicoureteral reflux. AB - BACKGROUND: Selection of the appropriate radiologic investigation in a child after first febrile urinary tract infection (UTI) remains a contentious issue. This report investigated the effectiveness of renal bladder ultrasound (RBUS) and late 6 month dimercaptosuccinic acid (DMSA) renal scan in the detection of high grade vesicoureteral reflux (VUR) after first febrile UTI in infants aged <1 year. METHODS: A total of 387 infants aged <1 year with first febrile UTI who completed diagnostic follow up consisting of RBUS, voiding cystourethrogram (VCUG) and late 6 month DMSA scan were enrolled in the study. The effectiveness of RBUS and DMSA scan in the detection of high-grade VUR, including cost and benefit were assessed. RESULTS: Abnormal RBUS was identified in 95 infants (24.5%). VUR was identified on VCUG in 79 (20.4%), of whom eight (2.1%) had high grade VUR (grade IV-V). Abnormal renal parenchyma was identified on late 6 month DMSA scan in 22 infants (5.7%). The sensitivity of abnormal RBUS and of late 6 month DMSA scan in the prediction of high-grade VUR was 50% and 87.5%, and the proportion of infants who avoided unnecessary VCUG was 75.5% and 94.3%, respectively. CONCLUSIONS: Fifty percent of high-grade VUR was not identified on RBUS screening after first febrile UTI. Although late 6 month DMSA scan had higher sensitivity in the detection of high-grade VUR, with the added benefit of detection of renal scars, the practical application of this method was limited due to its high cost, radiation exposure and the associated delay in decision making. PMID- 26275162 TI - Neglect and extinction in kinesthesia and thesesthesia: understanding proprioceptive inattention. AB - This paper describes a new observation of neglect and extinction of kinesthesia and thesesthesia (movement and position imperception), jointly reflecting proprioceptive inattention, in a series of patients with parietal lesions. A prototypical case is discussed in detail and unaddressed aspects of proprioceptive inattention are discussed through findings from four additional cases. Thesesthetic and kinesthetic extinction were tested through simultaneous antidromic vertical displacement of index fingers, while having patients report on finger proprioceptive perception with eyes closed. Patients had variable degrees of proprioceptive inattention affecting a specific limb, but without pallesthetic inattention or somatoagnosia, whereas symptoms often resolved with visual feedback or active limb movements. Findings support that kinesthesia and thesesthesia (a) are subserved by near-identical brain networks, (b) relate more to tactile perception than pallesthesia in higher order cortical areas, and (c) have a somatotopic cortical organization even in association brain areas. Furthermore, proprioceptive extinction and neglect involve (i) "attention network" structures, (ii) either hemisphere, (iii) gray or subcortical white matter damage, (iv) defective vigilance mechanisms possibly through premature habituation of spatiotemporally saturated neural capacitor circuits, and (v) are not the result of somatoagnosia, while (vi) their resolution is observed through reafferent motor-sensory or visual feedback. PMID- 26275164 TI - Comparison of the effects of Korean mindfulness-based stress reduction, walking, and patient education in diabetes mellitus. AB - The purpose of this study was to compare the effects of Korean mindfulness-based stress reduction (K-MBSR), walking, and patient education regarding diabetes mellitus (DM) on stress response, glycemic control, and vascular inflammation in patients with diabetes mellitus. A cluster randomized trial including 56 adults with diabetes mellitus (K-MBSR group = 21, walking group = 18, patient education group = 17) was conducted between 13 July and 14 September 2012. The questionnaire included the Diabetes Distress Scale and Perceived Stress Response Inventory. Fasting blood samples were used to measure levels of cortisol, blood glucose, plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (t-PA). There were no statistically significant differences between the effects of K-MBSR, walking, and patient education on stress, glycemic control, or vascular inflammation. However, in the K-MBSR and walking groups, significant reductions in the levels of serum cortisol and PAI-1 were observed. A significant reduction in psychological responses to stress was observed in the walking and patient education groups. Longitudinal studies could provide better insight into the impact of K-MBSR, walking, and patient education on health outcomes in adults with diabetes mellitus. PMID- 26275166 TI - A Comparison of Humiliation Measurement in a Depressive Versus Non-clinical Sample: A Possible Clinical Utility. AB - OBJECTIVE: We aimed to deepen the clinical utility of humiliation assessment in the study of depression. METHOD: We performed a correlational analysis of the relationship between humiliation, depression, resilience, and negative primary familial environment in 80 clinically depressed subjects (41 men and 39 women; mean age = 40.71, standard deviation SD = 9.94) and a strictly matched sample of 80 non-clinical subjects (41 men and 39 women; mean age = 40.64, SD = 10.24). We also implemented a hierarchical multiple regression analysis for each sample, to test the prediction of these variables on depression. RESULTS: Humiliation showed positive correlations with depressive factors, while negative correlations emerged with resilience in both samples. The hierarchical multiple regression analysis showed humiliation to be the most predictive factor of depression in the clinical sample only. CONCLUSION: This study improves the understanding of the relationship of humiliation and depression in both clinical and non-clinical populations. PMID- 26275167 TI - Reported serial positions of true and illusory memories in the Deese/Roediger/McDermott paradigm. AB - One of the easiest ways to induce illusory memories in the laboratory is to use the Deese-Roediger-McDermott (DRM) word-list paradigm. Researchers have used this paradigm not only to study people's memories of stimuli that were not actually presented, but also to study the phenomenological qualities of these illusions. In four experiments, the current investigation explored a phenomenological quality of illusory memories that has received almost no attention, specifically, temporality. A serial position task was incorporated into the DRM paradigm to examine temporal attributes of participants' true and false memories. Effects of list strength, presentation order, and types of warnings were examined. Results showed consistent serial position responses for true and false memories. However, only responses for illusory memories were affected by manipulations at study. The current findings thus lend support to encoding-based explanations of false recollections. PMID- 26275165 TI - Rule encoding in dorsal striatum impacts action selection. AB - Cognitive flexibility is a hallmark of prefrontal cortical (PFC) function yet little is known about downstream area involvement. The medial dorsal striatum (mDS) receives major projections from the PFC and is uniquely situated to perform the integration of responses with rule information. In this study, we use a novel rule shifting task in rats that mirrors non-human primate and human studies in its temporal precision and counterbalanced responses. We record activity from single neurons in the mDS while rats switch between different rules for reward. Additionally, we pharmacologically inactivate mDS by infusion of a baclofen/muscimol cocktail. Inactivation of mDS impaired the ability to shift to a new rule and increased the number of regressive errors. While recording in mDS, we identified neurons modulated by direction whose activity reflected the conflict between competing rule information. We show that a subset of these neurons was also rule selective, and that the conflict between competing rule cues was resolved as behavioural performance improved. Other neurons were modulated by rule, but not direction. These neurons became selective before behavioural performance accurately reflected the current rule. These data provide an additional locus for investigating the mechanisms underlying behavioural flexibility. Converging lines of evidence from multiple human psychiatric disorders have implicated dorsal striatum as an important and understudied neural substrate of flexible cognition. Our data confirm the importance of mDS, and suggest a mechanism by which mDS mediates abstract cognition functions. PMID- 26275168 TI - The Prevalence of Sickle Cell Disease and Its Implication for Newborn Screening in Germany (Hamburg Metropolitan Area). AB - Sickle cell disease is among hereditary diseases with evidence that early diagnoses and treatment improves the clinical outcome. So far sickle cell disease has not been included in the German newborn screening program despite immigration from countries with populations at risk. To determine the birth prevalence we tested 17,018 newborns. High pressure liquid chromatography and subsequent molecular-genetic testing were used for the detection and confirmation of hemoglobin variants. The frequency of sickle cell disease-consistent genotypes was one in 2,385 newborns. Duffy-blood group typing showed evidence that affected children were likely of Sub-Saharan ancestry. An inclusion of sickle cell disease into the German newborn screening seems reasonable. PMID- 26275169 TI - Salt metathesis versus protonolysis routes for the synthesis of silylamide Hauser base (R2NMgX; X = halogen) and amido-Grignard (R2NMgR) complexes. AB - The preparation of silylamide Hauser base (R2NMgX; X = halide) and amido-Grignard (R2NMgR) complexes from simple Grignard reagents using [K{N(SiMe2(t)Bu)2}]n, [K{N(SiMe2(t)Bu)(Si(i)Pr3)}]n and [K{N(Si(i)Pr3)2}]n, and their parent silylamines, was explored. Both salt metathesis and protonolysis routes proved ineffective with allylmagnesium chloride as a starting material due to complex Schlenk equilibria, with [Mg(N(RR'))(MU-Cl)(THF)]2 (N(RR') = {N(Si(t)BuMe2)2}(-), 1; {N(Si(t)BuMe2)(Si(i)Pr3)}(-), 2; {N(Si(i)Pr3)2}(-), 3) and [Mg{N(Si(i)Pr3)2}(MU-C3H5)]infinity (4) identified as minor products. In contrast, salt metathesis protocols using potassium silylamides and methylmagnesium iodide gave [Mg(N(RR'))(MU-CH3)]2 (N(RR') = {N(Si(t)BuMe2)2}(-), 7a; {N(Si(t)BuMe2)(Si(i)Pr3)}(-), 8; {N(Si(i)Pr3)2}(-), 9) and [Mg{N(Si(t)BuMe2)2}(CH3)(DME)] (7b), with [Mg{N(Si(t)BuMe2)2}(MU-I)(THF)]2 (10) isolated as a side-product during the preparation of 7a. Unusually, methylmagnesium iodide, di-n-butylmagnesium and 7-9 did not react with HN(RR') under the conditions we employed. The synthesis of [Na{N(Si(t)BuMe2)2}(THF)]2 (5a) and [Na{N(Si(t)BuMe2)2}(DME)2] (5b) from benzyl sodium and HN(Si(t)BuMe2)2, and a solvent-free structure of [K{N(Si(t)BuMe2)2}] (6), are also reported. Complexes 1, 5b, 7a, 7b, 8, 9 and 10 are fully characterised by single crystal XRD, multinuclear NMR and IR spectroscopy and elemental analysis, whereas complexes 2-4, 5a and 6 were identified by XRD only. PMID- 26275170 TI - Assembly of functionalized carbocycles or N-heterocycles through a domino electrocyclization-[1,2] migration reaction sequence. AB - The development of processes that streamline the synthesis of complex, functionalized carbocycles and heterocycles remains a hotly pursued topic because their scaffolds are present in a range of bioactive molecules and electronic materials. Although the Nazarov reaction has emerged to be useful in the synthesis of carbocycles and heterocycles, using an electrocyclization to trigger a migration remains underdeveloped. By constructing several bonds in one operation, domino reaction sequences are particularly effective at improving the efficiency of synthesis. The use of transition metal catalysts has the potential to render these processes stereoselective. This review examines the use of electrocyclization-[1,2] migrations to construct molecules and is organized by the type of ring constructed and the order of the two steps in this process. PMID- 26275171 TI - Demographic Responses to Oxidative Stress and Inflammation in the Wandering Albatross (Diomedea exulans). AB - One of the major challenges in ecological research is the elucidation of physiological mechanisms that underlie the demographic traits of wild animals. We have assessed whether a marker of plasma oxidative stress (TBARS) and plasma haptoglobin (protein of the acute inflammatory phase response) measured at time t predict five demographic parameters (survival rate, return rate to the breeding colony, breeding probability, hatching and fledging success) in sexually mature wandering albatrosses over the next four years (Diomedea exulans) using a five year individual-based dataset. Non-breeder males, but not females, having higher TBARS at time t had reduced future breeding probabilities; haptoglobin was not related to breeding probability. Neither TBARS nor haptoglobin predicted future hatching or fledging success. Haptoglobin had a marginally positive effect on female survival rate, while TBARS had a marginally negative effect on return rate. Our findings do not support the role for oxidative stress as a constraint of future reproductive success in the albatross. However, our data point to a potential mechanism underlying some aspects of reproductive senescence and survival. Our results also highlight that the study of the consequences of oxidative stress should consider the life-cycle stage of an individual and its reproductive history. PMID- 26275172 TI - Rhodopsin in the Dark Hot Sea: Molecular Analysis of Rhodopsin in a Snailfish, Careproctus rhodomelas, Living near the Deep-Sea Hydrothermal Vent. AB - Visual systems in deep-sea fishes have been previously studied from a photobiological aspect; however, those of deep-sea fish inhabiting the hydrothermal vents are far less understood due to sampling difficulties. In this study, we analyzed the visual pigment of a deep-sea snailfish, Careproctus rhodomelas, discovered and collected only near the hydrothermal vents of oceans around Japan. Proteins were solubilized from the C. rhodomelas eyeball and subjected to spectroscopic analysis, which revealed the presence of a pigment characterized by an absorption maximum (lambdamax) at 480 nm. Immunoblot analysis of the ocular protein showed a rhodopsin-like immunoreactivity. We also isolated a retinal cDNA encoding the entire coding sequence of putative C. rhodomelas rhodopsin (CrRh). HEK293EBNA cells were transfected with the CrRh cDNA and the proteins extracted from the cells were subjected to spectroscopic analysis. The recombinant CrRh showed the absorption maximum at 480 nm in the presence of 11 cis retinal. Comparison of the results from the eyeball extract and the recombinant CrRh strongly suggests that CrRh has an A1-based 11-cis-retinal chromophore and works as a photoreceptor in the C. rhodomelas retina, and hence that C. rhodomelas responds to dim blue light much the same as other deep-sea fishes. Because hydrothermal vent is a huge supply of viable food, C. rhodomelas likely do not need to participate diel vertical migration and may recognize the bioluminescence produced by aquatic animals living near the hydrothermal vents. PMID- 26275173 TI - Arginine-Vasopressin Receptor Blocker Conivaptan Reduces Brain Edema and Blood Brain Barrier Disruption after Experimental Stroke in Mice. AB - BACKGROUND: Stroke is a major cause of morbidity and mortality. Stroke is complicated by brain edema and blood-brain barrier (BBB) disruption, and is often accompanied by increased release of arginine-vasopressin (AVP). AVP acts through V1a and V2 receptors to trigger hyponatremia, vasospasm, and platelet aggregation which can exacerbate brain edema. The AVP receptor blockers conivaptan (V1a and V2) and tolvaptan (V2) are used to correct hyponatremia, but their effect on post ischemic brain edema and BBB disruption remains to be elucidated. Therefore, we conducted this study to investigate if these drugs can prevent brain edema and BBB disruption in mice after stroke. METHODS: Experimental mice underwent the filament model of middle cerebral artery occlusion (MCAO) with reperfusion. Mice were treated with conivaptan, tolvaptan, or vehicle. Treatments were initiated immediately at reperfusion and administered IV (conivaptan) or orally (tolvaptan) for 48 hours. Physiological variables, neurological deficit scores (NDS), plasma and urine sodium and osmolality were recorded. Brain water content (BWC) and Evans Blue (EB) extravasation index were evaluated at the end point. RESULTS: Both conivaptan and tolvaptan produced aquaresis as indicated by changes in plasma and urine sodium levels. However plasma and urine osmolality was changed only by conivaptan. Unlike tolvaptan, conivaptan improved NDS and reduced BWC in the ipsilateral hemisphere: from 81.66 +/- 0.43% (vehicle) to 78.28 +/- 0.48% (conivaptan, 0.2 mg, p < 0.05 vs vehicle). Conivaptan also attenuated the EB extravasation from 1.22 +/- 0.08 (vehicle) to 1.01 +/- 0.02 (conivaptan, 0.2 mg, p < 0.05). CONCLUSION: Continuous IV infusion with conivaptan for 48 hours after experimental stroke reduces brain edema, and BBB disruption. Conivaptan but not tolvaptan may potentially be used in patients to prevent brain edema after stroke. PMID- 26275175 TI - Does Diagnosis Make a Difference? Comparing Hospice Care Satisfaction in Matched Cohorts of Heart Failure and Cancer Caregivers. AB - BACKGROUND: Half of heart failure patients will die within five years of diagnosis, making them an ideal population for hospice to reach. Yet hospice originated in oncology, and problems have been noted with the enrollment of heart failure patients. Whether caregiver satisfaction, a key quality measure in hospice, differs between heart failure and cancer caregivers is unknown. OBJECTIVE: We aimed to determine whether diagnosis makes a difference in satisfaction with hospice care in matched cohorts of heart failure caregivers and cancer caregivers. METHODS: This was a national cohort study, using caregiver responses to the Family Evaluation of Hospice Care (FEHC) survey. Heart failure and cancer caregivers were matched via propensity scoring. The relationship between diagnosis and caregiver satisfaction was examined across the domains of symptom management, emotional support, caregiver teaching, coordination of care, and global satisfaction, both before and after matching via logistic regression. RESULTS: One-to-one matching with calipers yielded 7730 matched pairs out of an original sample of 8175 heart failure caregivers and 24,972 cancer caregivers. Significant differences were found in caregiver teaching, emotional support, coordination of care, and global satisfaction prior to matching, but the effect sizes were small. All differences disappeared after matching. High rates of dissatisfaction with caregiver teaching (42%) and emotional support (30%) were found in both cohorts. CONCLUSIONS: The diagnosis of heart failure, in and of itself, does not appear to make a difference in informal caregiver satisfaction with hospice care. Hospice provides high-quality care for patients, but improvements are needed in caring for the caregiver. PMID- 26275174 TI - Measurement of Heme Synthesis Levels in Mammalian Cells. AB - Heme serves as the prosthetic group for a wide variety of proteins known as hemoproteins, such as hemoglobin, myoglobin and cytochromes. It is involved in various molecular and cellular processes such as gene transcription, translation, cell differentiation and cell proliferation. The biosynthesis levels of heme vary across different tissues and cell types and is altered in diseased conditions such as anemia, neuropathy and cancer. This technique uses [4-(14)C] 5 aminolevulinic acid ([(14)C] 5-ALA), one of the early precursors in the heme biosynthesis pathway to measure the levels of heme synthesis in mammalian cells. This assay involves incubation of cells with [(14)C] 5-ALA followed by extraction of heme and measurement of the radioactivity incorporated into heme. This procedure is accurate and quick. This method measures the relative levels of heme biosynthesis rather than the total heme content. To demonstrate the use of this technique the levels of heme biosynthesis were measured in several mammalian cell lines. PMID- 26275176 TI - Brief Report: Doubly Robust Estimation of Standardized Risk Difference and Ratio in the Exposed Population. AB - Standardization-a method used to adjust for confounding-estimates counterfactual risks in a target population. To adjust for confounding variables that contain too many combinations to be fully stratified, two model-based standardization methods exist: regression standardization and use of an inverse probability of exposure weighted-reweighted estimators. Whereas the former requires an outcome regression model conditional on exposure and confounders, the latter requires a propensity score model. In reconciling among their modeling assumptions, doubly robust estimators, which only require correct specification of either the outcome regression or the propensity score model but do not necessitate both, have been well studied for total populations. Here, we provide doubly robust estimators of standardized risk difference and ratio in the exposed population. Theoretical details, simple model extension for independently censored outcomes, and a SAS program are provided in the eAppendix (http://links.lww.com/EDE/A955). PMID- 26275177 TI - Screening and Intervening on Alcohol and Other Drug Use in General Wellness Programs: Challenges and Opportunities. PMID- 26275178 TI - Seasonal Variation in the Occurrence of Rhegmatogenous Retinal Detachment. AB - PURPOSE: Seasonal predilection is reported in the occurrence of various systemic and ocular diseases. An attempt was made to evaluate the existence of such an association in the development of rhegmatogenous retinal detachment (RRD). The aims of the study were to investigate the existence of seasonal variation in the occurrence of RRD and to analyze the predisposing factors for such variation. DESIGN: This was a retrospective review. METHODS: A retrospective review of all cases of RRD during a period of 2 years (June 2012 to May 2014) was carried out. The details regarding demographic profile, clinical features, and the month of occurrence of RRD were collected. Climatic parameters such as temperature, relative humidity, rainfall, and number of sun hours were noted. The various factors were compared with SPSS version 17.0, and chi test was used for statistical analysis. RESULTS: Of the 76 cases of RRD, 38.2% occurred in the hot humid summer months (P = 0.046) followed by 22.4% in the cool humid winter months. Subtotal retinal detachments were more common in summer (P = 0.015). Factors suggestive of vitreous dehydration such as posterior vitreous detachment, intraocular pressure, and intraocular pressure of fellow eye were not associated with this seasonal variation. The peak minimum temperature, peak maximum temperature, and sun hours were related to this finding. High relative humidity and low rainfall were also associated. CONCLUSIONS: Rhegmatogenous retinal detachment shows definite seasonal variation which peaks in the summer months. Meteorological parameters may further play a role in determining the onset of retinal detachment. PMID- 26275179 TI - Trabeculectomy Under Augmented Topical Anesthesia: Study on Pain Evaluation and Surgical Feasibility. AB - PURPOSE: Performing trabeculectomy under topical anesthesia using lignocaine jelly with intracameral anesthesia may offer painless surgery with immediate visual gain and avoid the increase in intraocular pressure associated with locally injected anesthesia. In this context, we evaluated topical anesthesia using 2% lignocaine jelly with intracameral 1.0% lignocaine for trabeculectomy in terms of pain during surgery and the surgeon's experience. DESIGN: This was a tertiary care center-based interventional case series. METHODS: Patients scheduled for trabeculectomy as the first surgery for medically controlled glaucoma underwent standard ab externo trabeculectomy under topical anesthesia. Pain evaluation was done using a visual analog scale with the modified Wong-Baker FACES Pain Rating Scale, within 1 hour after surgery. RESULTS: Fifteen eyes of 14 patients were included in the study with a mean (SD, range) age of 61.3 (17.54, 40-90, distributed normally) years. Patients' pain score analysis showed a mean (SD, range) visual analog scale score of 0.73 (0.59, 0-2) on a scale of 0 to 10. The mean (SD, range) surgeon's satisfaction score was 3.2 (0.4, 3-4) on a scale of 3 to 9. The intraocular pressure of all patients was well controlled at 2 weeks [mean (SD, range), 9.2 (2.9, 4-16)] and at 4 weeks [mean (SD, range), 13.2 (1.2, 11-15)] postoperatively without any topical or systemic antiglaucoma medications. CONCLUSIONS: Trabeculectomy can be done under augmented topical anesthesia, which provides adequate analgesia for acceptable patient and surgeon comfort with favorable outcomes. Anesthesia provided by topical application of lignocaine 2% jelly and intracameral 1.0% lignocaine is sufficient for safe trabeculectomy surgery with acceptable discomfort to the patient. PMID- 26275180 TI - Effect of stride length on maximal pelvic tilt and hip extension during running. PMID- 26275181 TI - Radiation-Induced Necrosis of the Temporal Bone: Diagnosis and Management. AB - OBJECTIVE: To document our experience with osteoradionecrosis (ORN) of the temporal bone. STUDY DESIGN: Retrospective case review. SETTING: Tertiary care medical center. PATIENTS: Patients who developed exposed necrotic bone of the external auditory canal after radiation therapy to the head and neck. INTERVENTIONS: Temporal bone ORN was managed conservatively in all patients with a combination of systemic antibiotics, antibiotic ear drops, and in-office debridement. Three patients required surgery, two of which were for a cholesteatoma. MAIN OUTCOME MEASURE: The need for surgical intervention in the management of ORN. RESULTS: Twenty-three patients with ORN of the temporal bone comprise the study group. The average age of patients at the time of diagnosis was 58 years (range, 34-75 yr). The parotid gland was the most common primary tumor site (n = 10). The mean lag time from completion of radiotherapy to diagnosis of ORN was 11 years (range, 2-48 yr). The most common presenting symptom was hearing loss (n = 18), followed by tinnitus (n = 13) and otorrhea (n = 13). All 23 patients were managed conservatively with antibiotic therapy and in office debridement of necrotic bone. None of the patients required temporal bone resection and/or free-flap reconstruction. CONCLUSION: ORN of the temporal bone is a rare adverse event that can occur after radiotherapy for a variety of neoplasms of the head, neck, and central nervous system. Conservative management, which includes directed antibiotic therapy and regular in-office debridement of necrotic bone, can adequately control the disease process and symptomatology, thus avoiding more invasive surgical interventions. PMID- 26275182 TI - A Novel Radiographic Sign and a New Classifying System in Mastoiditis-Related Epidural Abscess. AB - OBJECTIVE: To describe a novel radiographic sign ("halo") and a new classification method of an evolving perisigmoid epidural abscess and present its correlation with intraoperative findings. STUDY DESIGN: Retrospective and prospective cohort study in a tertiary academic children's hospital. METHODS: The retrospective arm (15 children) was conducted between 1998 and 2007 and the prospective arm (11 children) between 2008 and 2013. The computerized tomographic appearance of the perisigmoid region was classified into four groups: Class I, normal; Class II, smooth halo; Class III, nodular halo 4 mm or less in diameter; and Class IV, gross nodular halo more than 4 mm in diameter. Intraoperative findings of the perisigmoid region were compared with the preoperative scan results. RESULTS: The correlation between preoperative imaging and intraoperative findings of the retrospective arm was highly significant (p = 0.007). The correlation between the preoperative imaging studies and intraoperative findings of the prospective arm was also highly significant (p = 0.005). The interobserver agreement for the proposed classification method was high (Cohen kappa score, 0.76; weighted kappa score, 0.84). CONCLUSION: A novel radiographic sign ("halo") and a new classification method for an evolving perisigmoid epidural abscess in acute mastoiditis are described. A thin and smooth halo sign is not indicative of a true abscess formation. Gross perisigmoid granular changes, however, are highly suggestive of an epidural abscess that warrants surgical intervention. PMID- 26275183 TI - Computer aided implantology: Changing trends. PMID- 26275184 TI - Publication ethics: Whose responsibility? PMID- 26275185 TI - Urinary 8-hydroxydeoxyguanosine as a marker of oxidative stress induced genetic toxicity in oral cancer patients. AB - CONTEXT: Recently, non-communicable diseases have snatched the lead from infectious diseases in causing mortality. Of these, oral cancer accounts for a significant proportion of deaths. Every year in India significant percentage of newly diagnosed malignancy is oral cancer attributed to various reasons. AIMS: The aim of this study was to assess the extent of oxidative stress and its effect on modification of DNA by urinary nucleoside 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in oral cancer subjects. To see the relationship between the nucleoside 8 OHdG and antioxidant capacity ferric reducing ability plasma (FRAP) in oral cancer subjects. SETTINGS AND DESIGN: Case-control study included three groups with 60 volunteers, who were divided into 30 controls, and equal number of clinically diagnosed oral cancer male patients: (Subdivided into newly diagnosed [n = 15] and 1-year treatment follow-up oral cancer subjects [n = 15]). MATERIALS AND METHODS: A random urine sample was used for analysis of 8-OHdG concentration. Serum triglycerides, lipid peroxidation, protein thiols, and FRAP assay were performed by spectrophotometric technique. STATISTICAL ANALYSIS USED: Student's t test and one-way analysis of variance were performed for group comparison and Pearson's correlation analysis were used. A P < 0.05 was considered the optimum level of significance. RESULTS: The urinary 8-OHdG and serum malondialdehyde levels were significantly elevated in newly diagnosed oral cancer subjects in their 1-year treatment compared to the control group (P < 0.05). A significant correlation was observed between urinary 8-OHdG and FRAP in both groups of oral cancer subjects. CONCLUSIONS: Urinary 8-OHdG can be a useful diagnostic marker of oxidative DNA damage in oral cancer subjects. PMID- 26275186 TI - Role of cardiovascular disease markers in periodontal infection: Understanding the risk. AB - CONTEXT: Both periodontitis and cardiovascular diseases (CVD) represent chronic inflammatory conditions, and periodontal infections have been postulated to perpetuate the progression of CVD's. However, limited evidence is available to prove the causal relationship. AIM: An effort in exploring this interrelation has been made in this study. The role of two inflammatory mediators, soluble CD40 ligand (sCD40 L) and monocyte chemoattractant protein-1 (MCP-1) has been established in progression and acute precipitation of CVD's. Due to a close link between these two mediators, the present study was designed to correlate the levels of sCD40 L and MCP-1 in serum and gingival crevicular fluid (GCF) of patients with chronic periodontitis. METHODS: Fifteen healthy and 30 patients of severe chronic periodontitis (diseased) participated in the study. Patients of the diseased group underwent scaling/root planning. The evaluation of plaque index, gingival index, probing depth, clinical attachment level, and a collection of serum and GCF samples was done at baseline and 6 weeks following periodontal therapy. The sCD40 L and MCP-1 levels were quantified using ELISA. RESULTS: The sCD40 L levels correlated strongly with MCP-1 levels in both GCF (r = 0.888) and serum (r = 0.861) in patients of chronic periodontitis. The relationship between the levels of the two markers was maintained in GCF (r = 0.868) and serum (r = 0.750) after Phase I periodontal therapy. CONCLUSIONS: The positive correlation observed suggests this pathway as one of the mechanisms that may lead to increasing severity of periodontal disease and its systemic effects. Further research efforts should be made in designing appropriate clinical trials, starting at an early stage and monitoring the potential benefits of maintenance of oral hygiene on cardiovascular health. PMID- 26275187 TI - Assessment of stability of orthodontic mini-implants under orthodontic loading: A computed tomography study. AB - OBJECTIVES: Miniscrews have been used in recent years for anchorage in orthodontic treatment. However, it is not clear whether the miniscrews are absolutely stationary or move when force is applied. This prospective clinical study was undertaken to evaluate the mobility of orthodontic miniscrews under orthodontic loading using computed tomography. MATERIALS AND METHODS: Ten adult patients (7 females and 3 males with mean age of 19 years, 7 mm overjet) who required en masse retraction of upper and lower anterior teeth infirst premolar extraction spaces were included in this study. After initial alignment of anterior teeth, the 0.019" *0.025" stainless steel archwire were placed in preadjusted edgewise appliance. The miniscrews (diameter - 1.3 mm, length - 7 mm) were inserted in between second premolar and thefirst molar in the maxilla (zygomatic buttress) and in mandible on the buccal side as direct anchorage. Immediately after placement of miniscrews without waiting period, NiTi coil springs (force of 150 g in the maxilla and 100 g in the mandible) were placed for the retraction. Denta Scans were taken immediately before force application (T1) and 6 months later (T2). The mean changes obtained at T1 and T2 in Denta Scans (axial plane, coronal plane, paraxial plane) were evaluated to determine any movement of different parts of miniscrews using one-way ANOVA test and Student's unpaired t-test. RESULTS: On average, miniscrews were extruded and tipped forward significantly, by 1 mm at the screw head in the axial plane (Group III) and 0.728 mm in the coronal plane (Group IV). Tail of miniscrews showed average tipping of 0.567 mm in the axial plane (Group I) and 0.486 mm in the paraxial plane (Group V). Least average mobility was shown by screw body of 0.349 mm in the axial plane (Group II). Clinically, no significant mobility was observed. CONCLUSION: Miniscrews are a stable anchorage for orthodontic tooth movement but do not remain absolutely stationary like an endosseous implant throughout orthodontic loading although miniscrews might move according to placement site, orthodontic loading, and inflammation of peri-implant tissue. Waiting period between miniscrews placement and orthodontic loading does not significantly affect the miniscrew mobility so immediate loading can be recommended. To prevent hitting any vital organs because of miniscrew mobility, it is recommended that they can be placed in a nontooth-bearing area that has no foramen, major nerves, or blood vessel pathway, or in a tooth-bearing area allowing a 1.5 mm safety clearance between the miniscrew and dental root. PMID- 26275188 TI - Effects of immediate and delayed intraradicular preparation on bond strength of fiber posts. AB - BACKGROUND: To assist the retention of restorations prepared in endodontically treated teeth, fiber posts are widely used in dental practice. The ideal time to prepare space for the post is still controversial. AIM: The purpose of this study was to evaluate the effects of immediate and delayed postspace preparation on the retention of the self-adhesive resin cement. MATERIALS AND METHODS: Twelve bovine teeth were used with sectioned roots standardized to 19 mm. The teeth were properly instrumented and filled with gutta-percha and eugenol-free cement AH Plus. Two experimental groups (n = 6) were created based on the different times of post preparation (immediate and delayed). Using cemented cylindrical fiber posts, the teeth were put in acrylic resin and polyvinyl chloride tubes, where the cuts were made. Two slices were obtained from the cervical third, two from the medium third and two from the apical third. Subsequently, the samples were subjected into push-out tests. Statistical analysis were performed using ANOVA and Tukey's test (P = 5%). RESULTS: The results indicated that, for all of the evaluated thirds, delayed preparation showed greater bond strength than immediate preparation. CONCLUSION: A delayed post preparation of the root space, following the root canal filling, is recommended. PMID- 26275189 TI - Dental fluorosis: A histological study using Light and Confocal microscopy. AB - AIMS: To observe and characterize the histological features of fluorosed teeth under light and confocal microscope (CFM). MATERIALS AND METHODS: A total of 25 fluorosed teeth and 5 normal teeth were collected from dentists across Dindigul, a known endemic area of fluorosis in South India. Ground sections of respective teeth were observed under light microscope and the sections were subsequently stained with acridine orange and studied under CFM. RESULTS: Histological changes were observed in the ground sections of fluorosed teeth as compared with the normal teeth. Depending on the degree of fluorosis, the affected teeth showed various features of hypomineralization in enamel and dentin. CONCLUSIONS: Fluoride interacts with both mineral phases and organic macromolecules by strong ionic and hydrogen bonds resulting in incomplete crystal growth at prism peripheries. This presents as hypomineralization of enamel and dentin. PMID- 26275190 TI - Evaluation of bleeding following dental extraction in patients on long-term antiplatelet therapy: A clinical trial. AB - OBJECTIVE: The aim of this trial was to evaluate the bleeding after dental extractions among patients on uninterrupted antiplatelet therapy. MATERIALS AND METHODS: A total of 190 patients under oral antiplatelet drugs requiring extraction of a single molar tooth were randomly assigned to two groups. Group A consisted of 95 patients on uninterrupted antiplatelet therapy and Group B consisted of 95 patients who have discontinued antiplatelet medication 5 days prior to extraction. The bleeding time of all patients was checked prior to extraction. The surgical procedure involved simple extraction of a single molar tooth under local anesthesia. The extraction socket was sutured with 3-0 silk. Pressure pack with gauze was given for 1 h. Bleeding after 1 h, 24 h, 48 h, and 5 days were compared between two groups. Chi-square test was used to compare the variables. P < 0.05 was taken as significant. RESULTS: None of the patients in either group had any significant uncontrollable bleeding after extraction. CONCLUSION: Hence, we recommend routine single tooth extractions in patients on long-term antiplatelet medication, without interruption or alteration of their medication. Such patients do not have an increased risk of prolonged or excessive postoperative bleeding. PMID- 26275191 TI - Cephalometric evaluation of condyle-fossa position in dentulous and edentulous subjects. AB - CONTEXT: Whenever there is loss of teeth and occlusion, it triggers a change in the functional and structural relationship of the mandible. Various physiologic factor such as age and changes in occlusion lead to specific remodeling changes in the temporomandibular joint (TMJ). AIMS: The aim of this study was to evaluate and compare the influence of dentition on condyle-fossa position by comparing this variable in dentulous and edentulous subjects using lateral cephalogram. SETTINGS AND DESIGN: The study was conducted on 25 dentulous and 25 edentulous subjects, comprising of males and females, visiting Yenepoya University, Mangalore. SUBJECTS AND METHODS: The age ranges of dentulous subjects were 25-30 years and edentulous subjects of 45-65 years with 1-5 years of edentulousness were chosen. Lateral cephalograms were taken, and various reference lines and planes were used to determine the center of condyle and center of the glenoid fossa. STATISTICAL ANALYSIS USED: The results were analyzed by SPSS version 7.0 (SPSS Inc., Chicago) and statistical analysis used was t-test. RESULTS: Condyle was placed upward and forward, and glenoid fossa was situated more anteriorly in edentulous subjects compared to dentulous subjects. CONCLUSIONS: This study supports the concept that TMJ is an articular triad with two points of contact provided by TMJ and third contact by the dentition. Alteration in any one of these contact points will produce secondary morphological changes in other two points. PMID- 26275192 TI - Fate of third molar in line of mandibular angle fracture - Retrospective study. AB - AIM: The study aimed to answer for the question whether a tooth in line of fracture predispose to complications such as infection and thereby warranting removal of the plates. MATERIALS AND METHODS: Surgically rehabilitated patients for unilateral angle of mandible fractures at author's center from 2000 to 2013 were considered in this study. During the study period, about 116 cases fulfilled the inclusion and exclusion criteria, and hence included in this study. All patients were treated by open, rigid fixation. RESULTS: During the fracture reduction and immobilization, 52.6% (n = 61) cases, the third molar was extracted and in 47.4% (n = 55) cases, the tooth was preserved. Only two cases of infection that required the plate removal occurred by 3 months and another one case within the next 6 months. When the tooth in question was removed, infection did not occur. In all, 52.72% (n = 29) of the 55 cases preserved were needs to be extracted for various reasons. The most common being periodontal causes followed by periapical pathology. Statistically the relationship between demographic data and outcome measures were analyzed using Chi-square test bivariate statistics. A P < 0.05 was taken as significant. CONCLUSION: The present study fails to identify any concrete factors that would predict the failure of the retained third molar that were involved in the line of mandibular fractures. The proof presented here, especially with low complication rates indicate that all impacted third molar along the line of fracture be removed and unless necessary, the partially erupted teeth would also be extracted. In such a situation, the rate of infection and survival of the third molar would have been entirely different. PMID- 26275193 TI - A 5-year retrospective study of rampant dental caries among adult patients in a Nigerian Teaching Hospital. AB - BACKGROUND: Rampant caries in adults has not been a focus of many researches unlike the childhood form of the disease. The disease is an interesting finding in an adult patient. When the condition occurs in children, it has been described as nursing bottle caries, baby bottle tooth decay, and the most recently adopted term, "early childhood caries". AIM: The aim was to determine the prevalence of rampant caries among adult patients. MATERIALS AND METHODS: Cases of rampant caries were identified from the records of all the patients treated during a 5 year period. Variables considered included the socio-demographic data, frequency of consumption of cariogenic diet, social habits, decayed, missing, filled teeth (DMFT), socioeconomic status (SES), and oral hygiene (OH), etc. Data were analyzed using student's t-test and one-way ANOVA for continuous variables, while Fishers exact test was adopted for categorical variables. Level of significance was set at P < 0.05. RESULT: Less than 1% (21 out of 3458) of patients treated during the period had adult rampant caries, but only 17 patients with complete data were analyzed. The age range of the patients was 22-61 years with a median of 36 years. The number of teeth with open carious cavities ranged from 8 to 18, with a mean of 11.6 +/- 3.3 teeth. A statistically significant difference was found in the number of open carious cavities and gender (P = 0.03), and between the SES and OH (P = 0.001). Patients in low SES had the poorest OH, The number of open carious lesion was higher in those that consumed refined sugar regularly. CONCLUSION: Occurrence of rampant caries was low and related to low socioeconomic status and regular consumption of cariogenic diet. PMID- 26275194 TI - Evaluation of salivary glucose, amylase, and total protein in Type 2 diabetes mellitus patients. AB - BACKGROUND: Diabetes mellitus is a complex multisystem metabolic disorder characterized by a deficit in the production of insulin. The oral complications of uncontrolled diabetes mellitus are devastating. Saliva is an organic fluid that can be collected noninvasively and by individuals with limited training. These reasons create an interest in evaluating the possibility of using saliva as a diagnostic tool. AIMS AND OBJECTIVES: The aim of this study was to determine, if saliva can be used as a noninvasive tool to monitor glycemic control in Type 2 diabetes. Comparative assessment of salivary (glucose, amylase, total protein levels) in patients with Type 2 diabetes and controls. MATERIALS AND METHODS: A total of 40 individuals, 20 with Type 2 diabetes and 20 controls of age group 40 60 years were selected for the study. Diabetic status was assessed by estimating random blood glucose levels. Unstimulated saliva was collected from each participant and investigated for glucose, amylase, and total protein levels. Salivary glucose estimation was performed using glucose-oxidase method, amylase by the direct substrate kinetic enzymatic method, and total protein by pyrogallol red dye end point method. All the parameters were subjected to statistical analysis using SPSS version 20.0. RESULTS: Significantly higher salivary glucose, lower amylase, and total proteins were observed in patients with Type 2 diabetes than controls. There was no significant correlation between salivary and blood glucose levels. CONCLUSION: These results suggest that diabetes influences the composition of saliva. Since a significant correlation was not observed between salivary and blood glucose levels, further research is needed to determine salivary glucose estimation as a diagnostic tool for diabetes mellitus. PMID- 26275195 TI - Ferro-concrete reinforcement of endodontically treated teeth with wide open apex. AB - AIM: The aim of the study was to compare the fracture resistance of roots obturated with mineral trioxide aggregate (MTA) obturation with post, MTA apical plug with Resilon obturation, MTA apical plug with gutta percha (GP) obturation, complete MTA obturation in teeth with wide open apex. MATERIALS AND METHODS: Fifty freshly extracted human maxillary central incisors were selected. Teeth were divided into four experimental groups (n = 10) and one control group (n = 10). Fifty teeth were separated, and roots of each tooth were standardized to a length of 12 mm. Access opening was done and instrumented with ProTaper F2 passed beyond the apex. The canals were then irrigated with 17% ethylenediaminetetraacetic acid and 3% sodium hypochlorite. Calcium hydroxide was placed in the canals for 7 days. The specimens were then divided into five groups. Group I: Apical plug MTA with metal post, Group II: Apical plug MTA with Resilon, Group III Apical plug MTA with GP, Group IV: Complete MTA obturation, and Group V: Control group. Fracture strength was measured using Instron testing machine at a speed of 5 mm/min, and the data were statistically analyzed using ANOVA and t-test. RESULTS: The roots reinforced with metallic post and MTA (Group 1) has the higher fracture strength when compared with other groups (P < 0.05). CONCLUSION: This Ferro-concrete reinforcement technique of MTA with the metallic post can be used in cases with wide open apex to increase the fracture resistance of tooth. PMID- 26275196 TI - Role of trabecular bone in visibility of laminadura: A cross-sectional radiographic study. AB - AIM: To determine the degree to which trabecular bone contributes to the radiographic visibility of laminadura (LD). STUDY DESIGN: Human dry mandibles were obtained, and a series of radiographs were acquired in the premolar region. Radiographs taken were: (1) Before removal of any bone, (2) After removal of small amount of cortical bone at the apex of tooth, (3) Removal of trabecular bone, (4) Smoothing of endosteal surface of cortical bone. The radiographs were projected to a panel of six oral radiologists, and they were asked to judge the visibility of LD. RESULTS: Chi-square analysis revealed a significant radiographic difference between radiographs made initially and after removal of trabecular bone, cortical bone and smoothing the endosteal surface of cortical bone. CONCLUSION: There was statistically significant difference in the visibility of loss of LD when trabecular bone is lost. LD can be visible only if the endosteal surface of the cortical bone and trabecular bone is intact. PMID- 26275197 TI - Correlation between the cytotoxicity of self-etching resin cements and the degree of conversion. AB - AIM: The aim of this study was to evaluate the correlation between the cytotoxicity and degree of conversion (DC) of self-etch resin cements with or without photopolymerization. MATERIALS AND METHODS: Three self-etching resin cements with or without photopolymerization were evaluated. Six test groups and one control group represented by a standardized L929-fibroblast cell culture were formed. The DC was measured by Fourier transform infrared spectrometry and was correlated with cell culture survival. STATISTICAL ANALYSIS: The analysis of variance and Bonferroni-Holm tests were applied (P < 0.05). RESULTS: The results show that, the cytotoxicity of self-etching resin cements is directly related to the DC. With the exception of Unicem, the other cements show some level of cytotoxicity, even with photopolymerization. CONCLUSION: These results indicate that photopolymerization of dual cure self-etching resin cements decrease toxic effects on cell culture. Adequate photopolymerization should be considered during cementation when using dual polymerization self-etching resin cements. PMID- 26275198 TI - Effects of different surface treatments on bond strength of an indirect composite to bovine dentin. AB - BACKGROUND: Several surface treatments could be used to improve the bond strength (BS) between indirect composites and cement. AIM: To evaluate the BS of an indirect composite submitted to different surface treatments, cemented to bovine dentin. SETTINGS AND DESIGN: One hundred and fifty conical cavities were prepared in slices of bovine dentin and bulk filled with the composite. MATERIALS AND METHODS: After curing and removal from the cavity, the restorations were treated according to the groups (n = 10): C-untreated, S-Sandblasting; SS-Sandblasting + silane; F-hydrofluoric acid; FS-hydrofluoric acid + silane; SF-Sandblasting + hydrofluoric acid; SFS-Sandblasting + hydrofluoric acid + silane; E-ethanol; ES ethanol + silane; SE-Sandblasting + ethanol; SES-Sandblasting + ethanol + silane; P-H2O2; PS-H2O2 + silane; SP-Sandblasting + H2O2; SPS-Sandblasting + H2O2 + silane. After cementation, push-out test was performed in a universal testing machine. STATISTICAL ANALYSIS: Data were submitted to nonparametric tests (Kruskal-Wallis and Mann-Whitney U-tests, alpha = 0.05). The failure mode was observed under a stereomicroscope and the topography by scanning electronic microscopy (SEM). RESULTS: Sandblasted groups led to the highest BS values, (P < 0.001), except for the SFS group. SE, SES, and SPS led to higher BS values than S and SS groups (P < 0.05). F, E and P groups showed the lowest BS values. The number of cohesive or mixed failures was related to higher BS values. SEM evaluation showed major irregularities only for sandblasted groups. CONCLUSIONS: Sandblasting was a safe surface treatment for the indirect composite, increasing the BS values. Hydrofluoric acid applied after sandblasting damaged the BS values and should not be recommended while ethanol and H2O2, when applied after sandblasting, were effective in increasing BS values. PMID- 26275199 TI - Expression of CD 68, CD 45 and human leukocyte antigen-DR in central and peripheral giant cell granuloma, giant cell tumor of long bones, and tuberculous granuloma: An immunohistochemical study. AB - BACKGROUND: Multinucleated giant cells (MNCs) form an integral part of numerous bone and soft tissue tumors, tumor-like lesions and are often associated with granulomas of immunological and nonimmunological origin. The presence of various types of giant cells depends on the lesions in which they are present which are difficult to be diagnosed under routine histological techniques. Immunohistochemistry can be used for a better diagnosis and understanding of the origin of various giant cells using various markers of immune response like human leukocyte antigen-DR (HLA-DR) and those expressed on monocytes and macrophages like CD 68 and leukocyte common antigen (LCA). MATERIALS AND METHODS: The study group consisted of 10 cases of giant cell tumor (GCT) of long bones, tuberculous granuloma, and giant cell granuloma to evaluate and analyze the expression pattern of LCA, CD 68, and HLA-DR in various giant cell lesions. RESULTS: Strong expression of CD 68 was observed in 80% of the lesions, strong and moderate expression of CD 45 observed in 70% of the lesions among and within the groups. In contrast, HLA-DR demonstrated negative expression in 80% of cases except for tuberculous granuloma where all the 10 cases showed moderate to strong immunoreactivity. CONCLUSION: CD 68 and CD 45 expression was found in central giant cell granuloma, peripheral giant cell granuloma and GCT, suggesting the origin from mononuclear phagocyte system and considering their clinical behavior of osteoclast type. High expressivity of HLA-DR in tuberculous granulomas which is an essential factor for presentation of the microbial antigen to CD 4 helper cells thus reassuring the fact that they are up-regulated in response to infection. PMID- 26275200 TI - Analysis of the effectiveness of calcium hydroxide removal with variation of technique and solvent vehicles. AB - CONTEXT: Calcium hydroxide (Ca(OH)2) paste filling is largely used as intra-canal medication and can be combined with different vehicles. Removal of that paste should be preceded by obturation, to avoid the occurrence of apical microleakage. AIMS: To evaluate the efficiency of removal of pulp Ca(OH)2, from using different vehicles (water, propylene glycol) and removal techniques (mechanical and ultrasonic). STUDY DESIGN: Twenty-four premolars and four human incisors were prepared with step-back technique and divided into six groups according to the removal techniques and vehicles used: Group distilled water/mechanical removal, Group distilled water/ultrasonic removal, Group propylene/mechanical removal, Group propylene/ultrasonic removal, negative control group, and positive control group. The differences between groups were analyzed. MATERIALS AND METHODS: The teeth were prepared by step-back technique. The samples were evaluated by stereomicroscopy, using a scoring system for the evaluation of residues in the canal. STATISTICAL ANALYSIS: Mann-Whitney test was used to a comparison between groups with the same vehicle. For comparison between groups, regardless of the vehicle, we used the Kruskal-Wallis test, considering P < 0.05 for both tests. RESULTS: Groups using distilled water or propylene glycol did not show statistically significant results. When the groups were compared, differences were detected between groups distilled water/propylene and mechanical removal/removal ultrasonic, with the first featuring superior performance. CONCLUSION: None of the removal techniques employed in this study was able to completely remove Ca(OH)2 from the root canal. However, the use of distilled water as a vehicle and ultrasonic removal presented the best performance. PMID- 26275201 TI - Effect of different surface treatments on microtensile bond strength of two resin cements to aged simulated composite core materials. AB - OBJECTIVE: Roughening of the aged composite resin core (CRC) surface seems essential for durable adhesion. The aim of this study was to investigate the influence of various surface treatments and different resin cements on microtensile bond strength (u TBS) between two aged core build-up composites (CBCs) and feldspathic ceramic. MATERIALS AND METHODS: A total of 16 composite blocks made of two CBCs, Core.it and Build-it were randomly assigned to four surface treatment groups after water storage and thermocycling (2 weeks and 500 cycles). Experimental groups included surface roughening with air abrasion (AA), hydrofluoric acid, pumice, and laser and then were bonded to computer-aided design/computer-aided manufacturing feldspathic ceramic blocks using two resin cements, Panavia F2 (PF), and Duo-link (DL). The u TBS was tested, and the fracture mode was assessed. The data were analyzed with multiple analysis of variance to estimate the contribution of different surface treatments, resin cements, and two aged CRCs on u TBS. Statistical significance level was set at alpha < 0.05. RESULTS: Surface treatment and cement type significantly affected bond strength (P < 0.001) but the type of CRC did not (P = 0.468). Between roughening methods, the highest and the lowest values of u TBS were sequentially obtained in AA and Er.YAG laser groups. The highest bond strength was in AA group cemented with PF (31.83 MPa). The most common failure mode was cohesive fracture in the cement. CONCLUSION: Different surface treatments had different effects on u TBS of aged CRCs to feldspathic ceramics. PF was significantly better than DL. PMID- 26275202 TI - Stability of interceptive/corrective orthodontic treatment for tooth ankylosis and Class II mandibular deficiency: A case report with 10 years follow-up. AB - The purpose of this article is to present the treatment of a 8-year-old boy with tooth ankylosis in teeth 85 and Class II division 1 malocclusion and to report a 10-year follow-up result. The patient was initially treated with a sagittal removable appliance, followed by an eruption guidance appliance and braces. The interceptive orthodontic treatment performed to recover the space lost by ankylosis of a deciduous tooth allowed a spontaneous eruption and prevented progression of the problem. The use of an eruption-guidance appliance corrected the dentoskeletal Class II, thus improving the patient's appearance. Besides the treatment producing a good occlusal relationship with the Class I molar, the correction of the overjet and overbite was stable over a ten-year period. PMID- 26275203 TI - Jaw - winking phenomenon: Report of a case with review of literature. AB - Jaw-winking or the Marcus Gunn phenomenon (MGP), a congenital uncommon condition characterized by involuntary elevation of a drooping upper eyelid concomitant with various movements of the mandible, is well-documented in medical literature, but very little information is available in dental literature. This is an interesting case report of a 17-year-old female with MGP, who reported for orthodontic treatment of her proclined upper anterior teeth, severe lower crowding, and mandibular micrognathia. Review of the literature revealed only two reported cases of dental anomalies in conjunction with MGP. The patient also gave a positive family history of MGP with a maternal cousin having a similar problem. Dentists and other oral health professionals can play a significant role in detection and diagnosis of this rare condition and should take protective measures during dental and oral surgical procedures. PMID- 26275204 TI - Pneumatization of the temporal portion of the zygomatic arch: The contribution of computed tomography to the reconstruction in volumetric two-dimensional and three dimensional, with the aid of image rendering protocols. AB - Pneumatization refers to the asymptomatic development of cavities containing air within them. There is great variability in the extent of temporal bone pneumatization. Nevertheless, in a few cases it extends to the zygomatic process. Images are presented in which the panoramic radiograph and hypocycloidal tomography reveal this variation from the norm, to which professionals must be alert, since the images may simulate the presence of pathology. In this case report we describe the presence of pneumatization of the petrous and zygomatic portions of the temporal bone, demonstrating the contribution of CT to reconstruction in volumetric 2D and 3D, with the aid of image rendering protocols. PMID- 26275205 TI - Enhancing retention of partial dentures using elastomeric retention rings. AB - This report presents an alternative method for the retention of partial dentures that relies on the engagement of tooth undercuts by a lining material. The lab procedures are also presented. A new maxillary and mandibular acrylic partial dentures were fabricated using elastomeric retention technique for a partially dentate patient. A partially dentate man reported difficulty in retaining his upper removable partial denture (RPD). The maxillary RPD was designed utilizing elastomeric retention technique. During follow-up, it was necessary to replace the retention rings due to wear. The replacement of the retention rings, in this case, was done through a chairside reline technique. Elastomeric retention technique provides exceptionally good retention can be indicated to stabilize, cushion, splint periodontally involved teeth, no enough undercut for clasps, eliminate extractions, single or isolated teeth. PMID- 26275206 TI - Perceived myths about oral health in India. PMID- 26275207 TI - Audio-visual recording of obtaining informed consent: Mandatory for clinical trials. PMID- 26275209 TI - Hierarchical Nanoporous Silica Films for Wear Resistant Antireflection Coatings. AB - High-performance antireflection (AR) layers were prepared by depositing hierarchical nanoporous silica films on glass substrates. We designed a composite layer consisting of mesoporous silica nanoparticles (MSNs) and a mesoporous silica matrix. The introduction of bimodal nanoporous structures, i.e., independent nanopore formation within the MSN and within the matrix, was achieved by using surface-protected MSNs and a polymeric nonionic surfactant template during the fabrication process. A porosity of more than 40% was achieved for composite AR materials. The protrusion of MSNs from the matrix led to spontaneous formation of nanoscale roughness on the surface of the coatings, which enhanced the AR properties. The solid bonding of the MSNs to the nanoporous matrices played an important role in the achievement of high mechanical durability. The optimal nanoporous coating, which contained ca. 50 wt % MSN, exhibited high transparency (91.5-97.5%) and low reflectance (<2.2%), over the whole range of visible light wavelengths, and sufficient wear resistance. PMID- 26275208 TI - Controlled Measurement and Comparative Analysis of Cellular Components in E. coli Reveals Broad Regulatory Changes in Response to Glucose Starvation. AB - How do bacteria regulate their cellular physiology in response to starvation? Here, we present a detailed characterization of Escherichia coli growth and starvation over a time-course lasting two weeks. We have measured multiple cellular components, including RNA and proteins at deep genomic coverage, as well as lipid modifications and flux through central metabolism. Our study focuses on the physiological response of E. coli in stationary phase as a result of being starved for glucose, not on the genetic adaptation of E. coli to utilize alternative nutrients. In our analysis, we have taken advantage of the temporal correlations within and among RNA and protein abundances to identify systematic trends in gene regulation. Specifically, we have developed a general computational strategy for classifying expression-profile time courses into distinct categories in an unbiased manner. We have also developed, from dynamic models of gene expression, a framework to characterize protein degradation patterns based on the observed temporal relationships between mRNA and protein abundances. By comparing and contrasting our transcriptomic and proteomic data, we have identified several broad physiological trends in the E. coli starvation response. Strikingly, mRNAs are widely down-regulated in response to glucose starvation, presumably as a strategy for reducing new protein synthesis. By contrast, protein abundances display more varied responses. The abundances of many proteins involved in energy-intensive processes mirror the corresponding mRNA profiles while proteins involved in nutrient metabolism remain abundant even though their corresponding mRNAs are down-regulated. PMID- 26275210 TI - Establishment of a bioluminescence model for microenvironmentally induced oral carcinogenesis with implications for screening bioengineered scaffolds. AB - BACKGROUND: Microenvironmental cues play a major role in head and neck cancer. Biodegradable scaffolds used for bone regeneration might also act as stimulative cues for head and neck cancer. The purpose of this study was to establish an experimental model for precise and noninvasive evaluation of tumorigenic potential of microenvironmental cues in head and neck cancer. METHODS: Bioluminescence was chosen to image tumor formation. Early neoplastic oral keratinocyte (DOK) cells were luciferase-transduced (DOK(Luc) ), then tested in nonobese diabetic severe combined immunodeficient IL2rgammanull mice either orthotopically (tongue) or subcutaneously for their potential as "screening sensors" for diverse microenvironmental cues. RESULTS: Tumors formed after inoculation of DOK(Luc) were monitored easier by bioluminescence, and bioluminescence was more sensitive in detecting differences between various microenvironmental cues when compared to manual measurements. Development of tumors from DOK(Luc) grown on scaffolds was also successfully monitored noninvasively by bioluminescence. CONCLUSION: The model presented here is a noninvasive and sensitive model for monitoring the impact of various microenvironmental cues on head and neck cancer in vivo. (c) 2015 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck 38: E1177-E1187, 2016. PMID- 26275211 TI - Recent Advances and Prospects of Cathode Materials for Sodium-Ion Batteries. AB - Sodium-ion batteries (SIBs) receive significant attention for electrochemical energy storage and conversion owing to their wide availability and the low cost of Na resources. However, SIBs face challenges of low specific energy, short cycling life, and insufficient specific power, owing to the heavy mass and large radius of Na(+) ions. As an important component of SIBs, cathode materials have a significant effect on the SIB electrochemical performance. The most recent advances and prospects of inorganic and organic cathode materials are summarized here. Among current cathode materials, layered transition-metal oxides achieve high specific energies around 600 mW h g(-1) owing to their high specific capacities of 180-220 mA h g(-1) and their moderate operating potentials of 2.7 3.2 V (vs Na(+) /Na). Porous Na3 V2 (PO4 )3 /C nanomaterials exhibit excellent cycling performance with almost 100% retention over 1000 cycles owing to their robust structural framework. Recent emerging cathode materials, such as amorphous NaFePO4 and pteridine derivatives show interesting electrochemical properties and attractive prospects for application in SIBs. Future work should focus on strategies to enhance the overall performance of cathode materials in terms of specific energy, cycling life, and rate capability with cationic doping, anionic substitution, morphology fabrication, and electrolyte matching. PMID- 26275212 TI - Perceptual grouping via binocular disparity: The impact of stereoscopic good continuation. AB - Stereoscopic contextual effects are widely reported but are generally discussed in terms of 2-D Gestalt grouping principles, e.g., good continuation or closure. We propose that there are disparity-based grouping operations that are separable from 2-D grouping and instead depend on the distribution of binocular disparity information. Two experiments assess the impact of perceptual grouping via good disparity continuation. First, perceived depth magnitude is reduced for a multidot contour with a smooth disparity gradient compared to the end points in isolation. This reduction is eliminated when disparity jitter is introduced to the intermediate dots. Second, observers showed more efficient visual search for the continuous contour versus the discontinuous version. Therefore, when there is spatial support for interpretation of a slanted object, quantitative depth is reduced, but is rapidly detected in visual search. These results reflect the operation of disparity-based grouping, extending the 2-D principle of good continuation into the third dimension. PMID- 26275213 TI - Smooth pursuit eye movements and motion perception share motion signals in slow and fast motion mechanisms. AB - Pursuit eye movements correlate with perceived motion in both velocity and direction, even without retinal motion. Cortical cells in the monkey medial temporal region generate signals for initiating pursuit eye movements and respond to retinal motion for perception. However, recent studies suggest multiple motion processes, fast and slow, even for low-level motion. Here we investigated whether the relationship with pursuit eye movements is different for fast and slow motion processes, using a motion aftereffect technique with superimposed low- and high spatial-frequency gratings. A previous study showed that the low- and high spatial-frequency gratings adapt the fast and slow motion processes, respectively, and that a static test probes the slow motion process and a flicker test probes the fast motion process (Shioiri & Matsumiya, 2009). In the present study, an adaptation stimulus was composed of two gratings with different spatial frequencies and orientations but the same temporal frequency, moving in the orthogonal direction of +/-45 degrees from the vertical. We measured the directions of perceived motion and pursuit eye movements to a test stimulus presented after motion adaptation with changing relative contrasts of the two adapting gratings. Pursuit eye movements were observed in the same direction as that of the motion aftereffects, independent of the relative contrasts of the two adapting gratings, for both the static and flicker tests. These results suggest that pursuit eye movements and perception share motion signals in both slow and fast motion processes. PMID- 26275214 TI - Monoclonal Antibodies Targeting the Alpha-Exosite of Botulinum Neurotoxin Serotype/A Inhibit Catalytic Activity. AB - The paralytic disease botulism is caused by botulinum neurotoxins (BoNT), multi domain proteins containing a zinc endopeptidase that cleaves the cognate SNARE protein, thereby blocking acetylcholine neurotransmitter release. Antitoxins currently used to treat botulism neutralize circulating BoNT but cannot enter, bind to or neutralize BoNT that has already entered the neuron. The light chain endopeptidase domain (LC) of BoNT serotype A (BoNT/A) was targeted for generation of monoclonal antibodies (mAbs) that could reverse paralysis resulting from intoxication by BoNT/A. Single-chain variable fragment (scFv) libraries from immunized humans and mice were displayed on the surface of yeast, and 19 BoNT/A LC-specific mAbs were isolated by using fluorescence-activated cell sorting (FACS). Affinities of the mAbs for BoNT/A LC ranged from a KD value of 9.0*10-11 M to 3.53*10-8 M (mean KD 5.38*10-9 M and median KD 1.53*10-9 M), as determined by flow cytometry analysis. Eleven mAbs inhibited BoNT/A LC catalytic activity with IC50 values ranging from 8.3 ~73*10-9 M. The fine epitopes of selected mAbs were also mapped by alanine-scanning mutagenesis, revealing that the inhibitory mAbs bound the alpha-exosite region remote from the BoNT/A LC catalytic center. The results provide mAbs that could prove useful for intracellular reversal of paralysis post-intoxication and further define epitopes that could be targeted by small molecule inhibitors. PMID- 26275215 TI - Early Neurodevelopmental Findings Predict School Age Cognitive Abilities in Duchenne Muscular Dystrophy: A Longitudinal Study. AB - OBJECTIVE: Neurodevelopmental and cognitive difficulties are known to occur frequently in boys with Duchenne muscular dystrophy but so far none of the published studies have reported both early neurodevelopmental assessments and cognitive tests in the same cohort. The aim of the present longitudinal study was to establish the correlation between early neurodevelopmental assessments performed in preschool boys and the cognitive scales performed at school age or later. METHODS: We performed cognitive tests at school age (mean age 5.7 year +/ 1.7 SD) (69 months+19 SD) in a cohort of Duchenne boys, previously assessed using the Griffiths scales before the age of 4 years (mean age when the Griffiths scales were performed 30 months +/-8.9 SD). RESULTS: The range of total Developmental quotients on the Griffiths ranged between 56 and 116 (mean 89 +/- 15.6 SD). The total Intelligence Quotients on the Wechsler scales ranged between 35 and 119 (mean 87 +/- 17.2 SD). There was a significant correlation between the findings on the two scales. P = <0.0001. When we subdivided the cohort according to site of mutations, there was a difference between boys with mutations upstream exon 44 and those with mutations in exon 44-45 affecting Dp140 on both Developmental and Intelligence Quotient (p 0.01 and p 0,003 respectively). CONCLUSIONS: Our results confirm that Duchenne boys tend to slightly underperform on both neurodevelopmental and cognitive assessments. Early neurodevelopmental findings correlated with the cognitive results obtained at school age with a clear concordance between subscales exploring similar domains on the two scales. PMID- 26275217 TI - Evidence-informed health policy making in Canada: past, present, and future. AB - Evidence-informed health policy making (EIHP) is becoming a necessary means to achieving health system reform. Although Canada has a rich and well documented history in the field of evidence-based medicine, a concerted effort to capture Canada's efforts to support EIHP in particular has yet to be realized. This paper reports on the development of EIHP in Canada, including promising approaches being used to support the use of evidence in policy making about complex health systems issues. In light of Canada's contributions, this paper suggests that scholars in Canada will continue engaging in the field of EIHP through further study of interventions underway, as well as by sharing knowledge within and beyond Canada's borders about approaches that support EIHP. PMID- 26275216 TI - Impact of the Regulators SigB, Rot, SarA and sarS on the Toxic Shock Tst Promoter and TSST-1 Expression in Staphylococcus aureus. AB - Staphylococcus aureus is an important pathogen manifesting virulence through diverse disease forms, ranging from acute skin infections to life-threatening bacteremia or systemic toxic shock syndromes. In the latter case, the prototypical superantigen is TSST-1 (Toxic Shock Syndrome Toxin 1), encoded by tst(H), and carried on a mobile genetic element that is not present in all S. aureus strains. Transcriptional regulation of tst is only partially understood. In this study, we dissected the role of sarA, sarS (sarH1), RNAIII, rot, and the alternative stress sigma factor sigB (sigmaB). By examining tst promoter regulation predominantly in the context of its native sequence within the SaPI1 pathogenicity island of strain RN4282, we discovered that sigmaB emerged as a particularly important tst regulator. We did not detect a consensus sigmaB site within the tst promoter, and thus the effect of sigmaB is likely indirect. We found that sigmaB strongly repressed the expression of the toxin via at least two distinct regulatory pathways dependent upon sarA and agr. Furthermore rot, a member of SarA family, was shown to repress tst expression when overexpressed, although its deletion had no consistent measurable effect. We could not find any detectable effect of sarS, either by deletion or overexpression, suggesting that this regulator plays a minimal role in TSST-1 expression except when combined with disruption of sarA. Collectively, our results extend our understanding of complex multifactorial regulation of tst, revealing several layers of negative regulation. In addition to environmental stimuli thought to impact TSST-1 production, these findings support a model whereby sporadic mutation in a few key negative regulators can profoundly affect and enhance TSST-1 expression. PMID- 26275218 TI - Prognostic Significance of Nuclear Phospho-ATM Expression in Melanoma. AB - UV radiation induced genomic instability is one of the leading causes for melanoma. Phosphorylation of Ataxia Telangiectasia Mutated (ATM) is one of the initial events that follow DNA damage. Phospho-ATM (p-ATM) plays a key role in the activation of DNA repair and several oncogenic pathways as well as in the maintenance of genomic integrity. The present study was therefore performed to understand the significance of p-ATM in melanoma progression and to correlate it with patient prognosis. Tissue microarray and immunohistochemical analysis were employed to study the expression of p-ATM in melanoma patients. A total of 366 melanoma patients (230 primary melanoma and 136 metastatic melanoma) were used for the study. Chi-square test, Kaplan-Meier, univariate and multivariate Cox regression analysis were used to elucidate the prognostic significance of p-ATM expression. Results revealed that both loss of, and gain in, p-ATM expression were associated with progression of melanoma from normal nevi to metastatic melanoma. Patients whose samples showed negative or strong p-ATM staining had significantly worse 5-year survival compared to patients who had weak to moderate expression. Loss of p-ATM expression was associated with relatively better 5-year survival, but the corresponding 10-year survival curve almost overlapped with that of strong p-ATM expression. p-ATM expression was found to be an independent prognostic factor for 5-year but not for 10-year patient survival. In conclusion our findings show that loss of p-ATM expression and gain-in p-ATM expression are indicators of worse melanoma patient survival. PMID- 26275219 TI - Antimicrobial Susceptibility of Bordetella bronchiseptica Isolates from Swine and Companion Animals and Detection of Resistance Genes. AB - Bordetella bronchiseptica causes infections of the respiratory tract in swine and other mammals and is a precursor for secondary infections with Pasteurella multocida. Treatment of B. bronchiseptica infections is conducted primarily with antimicrobial agents. Therefore it is essential to get an overview of the susceptibility status of these bacteria. The aim of this study was to comparatively analyse broth microdilution susceptibility testing according to CLSI recommendations with an incubation time of 16 to 20 hours and a longer incubation time of 24 hours, as recently proposed to obtain more homogenous MICs. Susceptibility testing against a panel of 22 antimicrobial agents and two fixed combinations was performed with 107 porcine isolates from different farms and regions in Germany and 43 isolates obtained from companion animals in Germany and other European countries. Isolates with increased MICs were investigated by PCR assays for the presence of resistance genes. For ampicillin, all 107 porcine isolates were classified as resistant, whereas only a single isolate was resistant to florfenicol. All isolates obtained from companion animals showed elevated MICs for beta-lactam antibiotics and demonstrated an overall low susceptibility to cephalosporines. Extension of the incubation time resulted in 1 2 dilution steps higher MIC50 values of porcine isolates for seven antimicrobial agents tested, while isolates from companion animals exhibited twofold higher MIC50/90 values only for tetracycline and cefotaxime. For three antimicrobial agents, lower MIC50 and MIC90 values were detected for both, porcine and companion animal isolates. Among the 150 isolates tested, the resistance genes blaBOR-1 (n = 147), blaOXA-2, (n = 4), strA and strB (n = 17), sul1 (n = 10), sul2 (n = 73), dfrA7 (n = 3) and tet(A) (n = 8) were detected and a plasmid localisation was identified for several of the resistance genes. PMID- 26275220 TI - Delta Neutrophil Index as a Marker for Differential Diagnosis between Acute Graft Pyelonephritis and Acute Graft Rejection. AB - INTRODUCTION: The delta neutrophil index (DNI) is the fraction of circulating immature granulocytes, which reflect infectious and/or septic condition. Acute graft pyelonephritis (AGPN) versus acute graft rejection is a frequently encountered diagnostic and therapeutic dilemma in kidney transplant recipients, but little is known about the clinical usefulness of DNI value in the differentiation of the two conditions. MATERIAL & METHODS: A total of 90 episodes of AGPN or acute graft rejection were evaluated at the Kangdong Sacred Heart Hospital between 2008 and 2014. We performed retrospective analysis of demographic, clinical, and laboratory parameters data. Receiver operating curves (ROC) and multivariate logistic regression were conducted to ascertain the utility of DNI in discriminating between AGPN and acute graft rejection. RESULTS: AGPN group had significantly higher DNI values than acute graft rejection group (2.9% vs. 1.9%, P < 0.001). The area under the ROC curve for DNI value to discriminate between AGPN and acute graft rejection was 0.85 (95% confidence interval [CI]; 0.76-0.92, P < 0.001). A DNI value of 2.7% was selected as the cut off value for AGPN, and kidney transplant recipients with a DNI value >= 2.7% were found to be at a higher risk of infection than those with a DNI < 2.7% (odd ratio [OR] 40.50; 95% CI 8.68-189.08; P < 0.001). In a multivariate logistic regression analysis, DNI was a significant independent factor for predicting AGPN after adjusting age, sex, log WBC count, log neutorphil count, log lymphocyte count, CRP concentration, and procalcitonin concentration (OR 4.32; 95% CI 1.81 10.34, P < 0.001). CONCLUSIONS: This study showed that DNI was an effective marker to differentiate between AGPN and acute graft rejection. Thus, these finding suggest that DNI may be a useful marker in the management of these patients. PMID- 26275221 TI - Metabolic and Behavioural Phenotypes in Nestin-Cre Mice Are Caused by Hypothalamic Expression of Human Growth Hormone. AB - The Nestin-Cre driver mouse line has mild hypopituitarism, reduced body weight, a metabolic phenotype and reduced anxiety. Although several causes have been suggested, a comprehensive explanation is still lacking. In this study we examined the molecular mechanisms leading to this compound phenotype. Upon generation of the Nestin-Cre mice, the human growth hormone (hGH) minigene was inserted downstream of the Cre recombinase to ensure efficient transgene expression. As a result, hGH is expressed in the hypothalamus. This results in the auto/paracrine activation of the GH receptor as demonstrated by the increased phosphorylation of signal transducer and activator of transcription 5 (STAT5) and reduced expression of growth hormone releasing hormone (Ghrh). Low Ghrh levels cause hypopituitarism consistent with the observed mouse growth hormone (mGH) deficiency. mGH deficiency caused reduced activation of the GH receptor and hence reduced phosphorylation of STAT5 in the liver. This led to decreased levels of hepatic Igf-1 mRNA and consequently postnatal growth retardation. Furthermore, genes involved in lipid uptake and synthesis, such as CD36 and very low-density lipoprotein receptor were upregulated, resulting in liver steatosis. In conclusion, this study demonstrates the unexpected expression of hGH in the hypothalamus of Nestin-Cre mice which is able to activate both the GH receptor and the prolactin receptor. Increased hypothalamic GH receptor signaling explains the observed hypopituitarism, reduced growth and metabolic phenotype of Nestin Cre mice. Activation of either receptor is consistent with reduced anxiety. PMID- 26275222 TI - Use of Recombinant Virus Replicon Particles for Vaccination against Mycobacterium ulcerans Disease. AB - Buruli ulcer, caused by infection with Mycobacterium ulcerans, is a necrotizing disease of the skin and subcutaneous tissue, which is most prevalent in rural regions of West African countries. The majority of clinical presentations seen in patients are ulcers on limbs that can be treated by eight weeks of antibiotic therapy. Nevertheless, scarring and permanent disabilities occur frequently and Buruli ulcer still causes high morbidity. A vaccine against the disease is so far not available but would be of great benefit if used for prophylaxis as well as therapy. In the present study, vesicular stomatitis virus-based RNA replicon particles encoding the M. ulcerans proteins MUL2232 and MUL3720 were generated and the expression of the recombinant antigens characterized in vitro. Immunisation of mice with the recombinant replicon particles elicited antibodies that reacted with the endogenous antigens of M. ulcerans cells. A prime-boost immunization regimen with MUL2232-recombinant replicon particles and recombinant MUL2232 protein induced a strong immune response but only slightly reduced bacterial multiplication in a mouse model of M. ulcerans infection. We conclude that a monovalent vaccine based on the MUL2232 antigen will probably not sufficiently control M. ulcerans infection in humans. PMID- 26275224 TI - Correction: G-Protein-Coupled Estrogen Receptor Agonist Suppresses Airway Inflammation in a Mouse Model of Asthma through IL-10. PMID- 26275223 TI - Satellite DNA Modulates Gene Expression in the Beetle Tribolium castaneum after Heat Stress. AB - Non-coding repetitive DNAs have been proposed to perform a gene regulatory role, however for tandemly repeated satellite DNA no such role was defined until now. Here we provide the first evidence for a role of satellite DNA in the modulation of gene expression under specific environmental conditions. The major satellite DNA TCAST1 in the beetle Tribolium castaneum is preferentially located within pericentromeric heterochromatin but is also dispersed as single repeats or short arrays in the vicinity of protein-coding genes within euchromatin. Our results show enhanced suppression of activity of TCAST1-associated genes and slower recovery of their activity after long-term heat stress relative to the same genes without associated TCAST1 satellite DNA elements. The level of gene suppression is not influenced by the distance of TCAST1 elements from the associated genes up to 40 kb from the genes' transcription start sites, but it does depend on the copy number of TCAST1 repeats within an element, being stronger for the higher number of copies. The enhanced gene suppression correlates with the enrichment of the repressive histone marks H3K9me2/3 at dispersed TCAST1 elements and their flanking regions as well as with increased expression of TCAST1 satellite DNA. The results reveal transient, RNAi based heterochromatin formation at dispersed TCAST1 repeats and their proximal regions as a mechanism responsible for enhanced silencing of TCAST1-associated genes. Differences in the pattern of distribution of TCAST1 elements contribute to gene expression diversity among T. castaneum strains after long-term heat stress and might have an impact on adaptation to different environmental conditions. PMID- 26275225 TI - New techniques in antibiotic discovery and resistance: Raman spectroscopy. AB - Raman spectroscopy can play a role in both antibiotic discovery and understanding the molecular basis of resistance. A major challenge in drug development is to measure the population of the drug molecules inside a cell line and to follow the chemistry of their reactions with intracellular targets. Recently, a protocol based on Raman microscopy has been developed that achieves these goals. Drug candidates are soaked into live bacterial cells and subsequently the cells are frozen and freeze-dried. The samples yield exemplary (nonresonance) Raman data that provide a measure of the number of drug molecules within each cell, as well as details of drug-target interactions. Results are discussed for two classes of compounds inhibiting either beta-lactamase or dihydrofolate reductase enzymes in a number of Gram-positive or Gram-negative cell lines. The advantages of the present protocol are that it does not use labels and it can measure the kinetics of cell-compound uptake on the time scale of minutes. Spectroscopic interpretation is supported by in vitro Raman experiments. Studying drug-target interactions in aqueous solution and in single crystals can provide molecular level insights into drug-target interactions, which, in turn, provide the underpinnings of our understanding of data from bacterial cells. Thus, the applicability of X-ray crystallographic-derived data to in-cell chemistry can be tested. PMID- 26275226 TI - Nontarget analysis of Murchison soluble organic matter by high-field NMR spectroscopy and FTICR mass spectrometry. AB - High-field NMR spectra of Murchison meteorite methanolic extracts revealed primarily aliphatic extraterrestrial organic matter (EOM) with near statistical branching of commonly C(3-5) units separated by heteroatoms and aromatic units. The ratios of CCH, OCH and C(sp2)H units were 89 : 8 : 3, whereas carbon-based aliphatic chain termination was in the order methyl > -COOH > -CH(CH3)COOH. Aliphatic methine carbon was abundant, but its weak NMR signatures were primarily deduced from JRES (J-resolved) NMR spectra. Carbon NMR spectra were dominated by methylene and methyl carbon; strong apodization revealed methine carbon, of which about 20% was aromatic. Extrapolation provided 5-7% aromatic carbon present in Murchison soluble EOM. Compositional heterogeneity in Murchison methanolic extracts was visible in NMR and Fourier transform ion cyclotron (FTICR) mass spectra obtained from a few cubic millimeters of solid Murchison meteorite; increasing sample size enhanced uniformity of NMR spectra. Intrinsic chemical diversity and pH-dependent chemical shift variance contributed to the disparity of NMR spectra. FTICR mass spectra provided distinct clustering of CHO/CHOS and CHNO/CHNOS molecular series and confirmed the prevalence of aliphatic/alicyclic (73%) over single aromatic (21%) and polyaromatic (6%) molecular compositions, suggesting extensive aliphatic substitution of aromatic units as proposed by NMR. Murchison soluble EOM molecules feature a center with enhanced aromatic and heteroatom content, which provides rather diffuse and weak NMR signatures resulting from a huge overall chemical diversity. The periphery of Murchison EOM molecules comprises flexible branched aliphatic chains and aliphatic carboxylic acids. These project on narrow ranges of chemical shift, facilitating observation in one-dimensional and two-dimensional NMR spectra. The conformational entropy provided by these flexible surface moieties facilitates the solubility of EOM. PMID- 26275228 TI - Clinical Research in Vulnerable Populations: Variability and Focus of Institutional Review Boards' Responses. AB - BACKGROUND: Children and patients with cognitive deficits may find it difficult to understand the implication of research. In the European Union (EU), clinical studies outside the EU directives concerning medicinal products or medical devices, i.e., "miscellaneous clinical studies", have no legally mandated timelines for institutional review boards' (IRB) decisions. GOAL: To evaluate the review process of IRBs for two different "miscellaneous" multicenter clinical research protocols involving vulnerable subjects (children and adult stroke patients). METHODS: Descriptive and comparative statistics. Protocol 1 is a prospective, multicenter, cross-sectional screening study of a symptomatic pediatric population at risk for Fabry disease involving genetic testing (NCT02152189). Protocol 2 is a prospective, multicenter, randomized, controlled, open-label, blinded endpoint post-market study to evaluate the effectiveness of stent retrievers (NCT02135926). After having obtained positive initial IRB votes at the main study site, both protocols were subsequently submitted to the remaining IRBs. RESULTS: Protocol 1 was submitted to 19 IRBs. No IRB objected to the study. Median time-to-final vote was 34 (IQR 10-65; range 0 to 130) days. Two IRBs accepted the coordinating center's IRB votes without re-evaluation. Changes to the informed consent documents were asked by 7/19 IRBs, amendments to the protocol by 2. Protocol 2 was submitted to 16 IRBs. Fifteen decisions were made. No IRB objected to the study. Median time-to final vote was 59 (IQR 10 to 65; range 0 to 128) days, which was not statistically significantly different compared with protocol 1 (Wilcoxon test). Two IRBs accepted a previous IRB decision and did not conduct an independent review. Eight/16 IRBs required changes to the informed consent documents; two IRBs recommended an amendment of the protocol. CONCLUSION: Both clinical research protocols involving vulnerable populations were well accepted. IRB workflows and decision times varied substantially. Some IRBs accepted a previous IRB decision without the necessity of another reevaluation process. Requested changes were focused on the informed consent documents. A more standardized approach across jurisdictions is desirable. PMID- 26275229 TI - Emmental Cheese Environment Enhances Propionibacterium freudenreichii Stress Tolerance. AB - Dairy propionibacteria are actinomycetales found in various fermented food products. The main species, Propionibacterium freudenreichii, is generally recognized as safe and used both as probiotic and as cheese starter. Its probiotic efficacy tightly depends on its tolerance towards digestive stresses, which can be largely modulated by the ingested delivery vehicle. Indeed, tolerance of this bacterium is enhanced when it is consumed within a fermented dairy product, compared to a dried probiotic preparation. We investigated both stress tolerance and protein neosynthesis upon growth in i) chemically defined or ii) aqueous phase of Emmental cheeses. Although the same final population level was reached in both media, a slower growth and an enhanced survival of CIRM BIA 1 strain of P. freudenreichii subsp. shermanii was observed in Emmental juice, compared to chemically defined medium. This was accompanied by differences in substrates used and products released as well as overexpression of various early stress adaptation proteins in Emmental juice, compared to chemically defined medium, implied in protein folding, in aspartate catabolism, in biosynthesis of valine, leucine and isoleucine, in pyruvate metabolism in citrate cycle, in the propionate metabolism, as well as in oxidoreductases. All these changes led to a higher digestive stress tolerance after growth in Emmental juice. Mechanisms of stress adaptation were induced in this environment, in accordance with enhanced survival. This opens perspectives for the use of hard and semi-hard cheeses as delivery vehicle for probiotics with enhanced efficacy. PMID- 26275230 TI - Intraspecies Genomic Diversity and Long-Term Persistence of Bifidobacterium longum. AB - Members of genus Bifidobacterium are Gram-positive bacteria, representing a large part of the human infant microbiota and moderately common in adults. However, our knowledge about their diversity, intraspecific phylogeny and long-term persistence in humans is still limited. Bifidobacterium longum is generally considered to be the most common and prevalent species in the intestinal microbiota. In this work we studied whole genome sequences of 28 strains of B. longum, including 8 sequences described in this paper. Part of these strains were isolated from healthy children during a long observation period (up to 10 years between isolation from the same patient). The three known subspecies (longum, infantis and suis) could be clearly divided using sequence-based phylogenetic methods, gene content and the average nucleotide identity. The profiles of glycoside hydrolase genes reflected the different ecological specializations of these three subspecies. The high impact of horizontal gene transfer on genomic diversity was observed, which is possibly due to a large number of prophages and rapidly spreading plasmids. The pan-genome characteristics of the subspecies longum corresponded to the open pan-genome model. While the major part of the strain-specific genetic loci represented transposons and phage-derived regions, a large number of cell envelope synthesis genes were also observed within this category, representing high variability of cell surface molecules. We observed the cases of isolation of high genetically similar strains of B. longum from the same patients after long periods of time, however, we didn't succeed in the isolation of genetically identical bacteria: a fact, reflecting the high plasticity of microbiota in children. PMID- 26275231 TI - Barriers to Point-of-Care Testing in India: Results from Qualitative Research across Different Settings, Users and Major Diseases. AB - BACKGROUND: Successful point-of-care testing, namely ensuring the completion of the test and treat cycle in the same encounter, has immense potential to reduce diagnostic and treatment delays, and impact patient outcomes. However, having rapid tests is not enough, as many barriers may prevent their successful implementation in point-of-care testing programs. Qualitative research on diagnostic practices may help identify such barriers across different points of care in health systems. METHODS: In this exploratory qualitative study, we conducted 78 semi-structured interviews and 13 focus group discussions in an urban and rural area of Karnataka, India, with healthcare providers (doctors, nurses, specialists, traditional healers, and informal providers), patients, community health workers, test manufacturers, laboratory technicians, program managers and policy-makers. Participants were purposively sampled to represent settings of hospitals, peripheral labs, clinics, communities and homes, in both the public and private sectors. RESULTS: In the Indian context, the onus is on the patient to ensure successful point-of-care testing across homes, clinics, labs and hospitals, amidst uncoordinated providers with divergent and often competing practices, in settings lacking material, money and human resources. We identified three overarching themes affecting point-of-care testing: the main theme is 'relationships' among providers and between providers and patients, influenced by the cross-cutting theme of 'infrastructure'. Challenges with both result in 'modified practices' often favouring empirical (symptomatic) treatment over treatment guided by testing. CONCLUSIONS: Even if tests can be conducted on the spot and infrastructure challenges have been resolved, relationships among providers and between patients and providers are crucial for successful point-of care testing. Furthermore, these barriers do not act in isolation, but are interlinked and need to be examined as such. Also, a test alone has only limited power to overcome those difficulties. Test developers, policy-makers, healthcare providers and funders need to use these insights in overcoming barriers to point of-care testing programs. PMID- 26275232 TI - Clast rind analysis using multi-high resolution instrumentation. AB - Clast weathering rinds, formed over varying lengths of time (10(2) -10(6) years) in terrestrial environments, are measured to provide relative ages for deposits in glacial sequences, specifically to differentiate between glaciations, occasionally within glaciations. Other studies have sought to reveal weathering rates in non-glacial environments using microscopic techniques and isotopes. Recent analyses of clast rinds from tropical, mid-latitude and polar areas reveal an astounding corpus of organic and inorganic paleoenvironmental data derived from atmospheric and biospheric elements active in weathering clasts in glacial deposits over varying lengths of time. In some cases, extreme biochemical products, observed within the rind matrix, are seen to play a role in adjusting redox potentials important in the production of oxides and hydroxides and biominerals with variable compositions. Up to recently, rind analysis has been limited to use of the light microscope and SEM/EDS, which has greatly advanced our understanding of compositional inter-linkages of minerals and biotic elements, but only along horizontal axes within the rind. A test involving rind surface composition using vertical axis nanospaced layer analysis within rinds using focused ion beam (FIB) and TEM/STEM/EDX imagery and chemistry illustrates the power of data acquisition within the three-dimensional weathered archive. SCANNING 38:202-212, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26275233 TI - Facile Enzymatic Synthesis of Ketoses. AB - Studies of rare ketoses have been hampered by a lack of efficient preparation methods. A convenient, efficient, and cost-effective platform for the facile synthesis of ketoses is described. This method enables the preparation of difficult-to-access ketopentoses and ketohexoses from common and inexpensive starting materials with high yield and purity and without the need for a tedious isomer separation step. PMID- 26275234 TI - Rituximab and low-dose cyclosporine combination therapy for steroid-resistant focal segmental glomerulosclerosis. AB - BACKGROUND: We investigated the efficacy of rituximab and low-dose cyclosporine combination therapy for focal segmental glomerulosclerosis (FSGS) in children with steroid-resistant nephrotic syndrome (SRNS). METHODS: Five FSGS children with SRNS were treated twice with rituximab and low-dose cyclosporine (CyA) combination therapy (RTX-CyAT). The clinical features and laboratory data were investigated before and after RTX-CyAT, and the outcomes were assessed. RESULTS: Prednisolone (PSL) was discontinued 3 months after RTX-CyAT in all patients. The number of CD19-positive cells decreased to <1% of all white blood cells in all patients at 1 month after RTX-CyAT, and was maintained at this level for 259.6 +/ 68.2 days. All patients remained in remission for the duration of the decrease in CD19-positive cells to <1%. Two patients also remained in remission throughout the observation period, with three patients having a single relapse at 333 +/- 89 days (range, 231-376 days) after RTX-CyAT. In all patients, the mean steroid and CyA doses after RTX-CyAT were lower than those before RTX-CyAT. CONCLUSIONS: RTX CyAT is effective in FSGS patients with SRNS and may ameliorate the side-effects of PSL and immunosuppressive drugs. PMID- 26275235 TI - Development and psychometric testing of a semantic differential scale of sexual attitude for the older person. AB - The purpose of this study was to develop and test a semantic differential scale of sexual attitudes for older people in Korea. The scale was based on items derived from a literature review and focus group interviews. A methodological study was used to test the reliability and validity of the instrument. A total of 368 older men and women were recruited to complete the semantic differential scale. Fifteen pairs of adjective ratings were extracted through factor analysis. Total variance explained was 63.40%. To test for construct validity, group comparisons were implemented. The total score of sexual attitudes showed significant differences depending on gender and availability of sexual activity. Cronbach's alpha coefficient for internal consistency was 0.96. The findings of this study demonstrate that the semantic differential scale of sexual attitude is a reliable and valid instrument. PMID- 26275236 TI - Differential effects of cathodal transcranial direct current stimulation of prefrontal, motor and somatosensory cortices on cortical excitability and pain perception - a double-blind randomised sham-controlled study. AB - The primary aim of this study was to assess the effects of cathodal transcranial direct current stimulation (c-tDCS) over cortical regions of the pain neuromatrix, including the primary motor (M1), sensory (S1) and dorsolateral prefrontal (DLPFC) cortices on M1/S1 excitability, sensory (STh), and pain thresholds (PTh) in healthy adults. The secondary aim was to evaluate the placebo effects of c-tDCS on induced cortical and behavioural changes. Before, immediately after and 30 min after c-tDCS the amplitude of N20-P25 components of somatosensory evoked potentials (SEPs) and peak-to-peak amplitudes of motor evoked potentials (MEPs) were measured under four different experimental conditions. STh and PTh for peripheral electrical and mechanical stimulation were also evaluated. c-tDCS of 0.3 mA was applied for 20 min. A blinded assessor evaluated all outcome measures. c-tDCS of M1, S1 and DLPFC significantly decreased the corticospinal excitability of M1 (P < 0.05) for at least 30 min. Following the application of c-tDCS over S1, M1 and DLPFC, the amplitude of the N20-P25 component of SEPs decreased for at least 30 min (P < 0.05). Compared with baseline values, significant STh and PTh increases were observed after c-tDCS of these three sites. Decreasing the level of S1 and M1 excitability, following S1, M1 and DLPFC stimulation, confirmed the functional connectivities between these cortical sites involved in pain processing. Furthermore, increasing the level of STh/PTh after c-tDCS of these sites indicated that stimulation of not only M1 but also S1 and DLPFC could be considered a technique to decrease the level of pain in patients. PMID- 26275237 TI - Supersampling and Network Reconstruction of Urban Mobility. AB - Understanding human mobility is of vital importance for urban planning, epidemiology, and many other fields that draw policies from the activities of humans in space. Despite the recent availability of large-scale data sets of GPS traces or mobile phone records capturing human mobility, typically only a subsample of the population of interest is represented, giving a possibly incomplete picture of the entire system under study. Methods to reliably extract mobility information from such reduced data and to assess their sampling biases are lacking. To that end, we analyzed a data set of millions of taxi movements in New York City. We first show that, once they are appropriately transformed, mobility patterns are highly stable over long time scales. Based on this observation, we develop a supersampling methodology to reliably extrapolate mobility records from a reduced sample based on an entropy maximization procedure, and we propose a number of network-based metrics to assess the accuracy of the predicted vehicle flows. Our approach provides a well founded way to exploit temporal patterns to save effort in recording mobility data, and opens the possibility to scale up data from limited records when information on the full system is required. PMID- 26275238 TI - The Effect of Soft Tissue on Temperature Estimation from Burnt Bone Using Fourier Transform Infrared Spectroscopy. AB - This study investigated the effect of soft tissue and different exposure times on the prediction of burning temperatures of bone when using Fourier transform infrared spectroscopy (FTIR). Ovis aries rib bones were burnt at different temperatures and for varying time intervals. Results of a linear regression analysis indicated that burn temperatures can be predicted with a standard error of +/-70 degrees C from defleshed bone spectra. Exposure time does not have a significant impact on prediction accuracy. The presence of soft tissue has a significant impact on heat-induced changes of the bone matrix in low (<300 degrees C) as well as high temperatures (>800 degrees C), slowing down combustion in the former and accelerating it in the latter (p < 0.05). At medium temperatures, no significant difference was noted. These results provide forensic investigators a new perspective with which to interpret the results of crystallinity measures derived from burnt bone. PMID- 26275239 TI - Patient-Reported Functional and Quality of Life Outcomes in a Large Cohort of Long-Term Survivors of Ewing Sarcoma. AB - BACKGROUND: Little data exist regarding long-term functional and quality of life (QOL) outcomes for survivors of Ewing sarcoma (ES). Specifically, there are few reports assessing the impact of patient characteristics and local therapy modalities on patient-reported outcomes (PRO). PROCEDURE: Long-term survivors of ES treated between 1977 and 2009 completed self-assessed functional and QOL surveys, using the Toronto Extremity Salvage Score (TESS) and PEDSQL 4.0 generic core instruments, respectively. Statistical analyses were performed to correlate these outcomes to clinical presentations and treatment regimens. RESULTS: Subjects (n = 74) with a mean duration from diagnosis of 17.8 years completed the survey. Mean TESS and PEDSQL total scores for the entire cohort were 93.0 +/- 10.3 and 81.6 +/- 18.0, respectively. No significant differences were appreciated between adult and pediatric patients, although increasing age was associated with lower functional scores (P = 0.04). Mean PEDSQL total scores were significantly lower for female patients (74.6 +/- 19.7) compared to males (85.7 +/- 15.7) (P = 0.01). Mild to moderate disability was reported by 32% of respondents and was associated with lower TESS and PEDSQL scores. Local control modality did not significantly affect functional and QOL scores. Patients with pelvic tumors had significantly lower TESS scores compared to those with nonpelvic tumors (P = 0.04), especially amongst patients treated with both surgery and radiation. CONCLUSIONS: Although many survivors of ES report excellent functional and QOL outcomes, a significant number report long-term disability and impairments. Older patients, females, and those with pelvic primary tumors appear at the greatest risk for long-term decrements and may benefit from early therapeutic interventions. PMID- 26275240 TI - Report of the ASFA apheresis registry study on Wilson's disease. AB - PURPOSE: Wilson's disease is a rare autosomal recessive genetic disorder that results in accumulation of copper in the liver, brain, cornea and kidney. Therapeutic plasma exchange (TPE) has been used to remove copper and provide a bridge to liver transplantation. We report here the collective experiences through the ASFA apheresis registry on Wilson's disease. METHODS: The ASFA apheresis registry is a multi-center registry study. Both prospective and retrospective data, with the latter involving data collection back to January 2000 are entered in the registry. The registry includes patient demographics, apheresis procedural information, treatment schedules, and treatment outcomes and complications. RESULTS: A total of 10 patients (3 males and 7 females) with Wilson's disease treated between 2005 and 2013 were included. Median age of first diagnosis and first TPE were 16 and 17 years, respectively. Via central venous access, these patients underwent a total of 43 TPEs; the median number of TPE procedures per patient was 3.5. All of the TPEs used ACD-A as anticoagulation, 42/43 TPEs targeted 1-1.25 plasma volumes, and 41/43 TPEs were performed with 100% fluid balance. Post TPE procedures, 9 patients underwent liver transplantation; all 10 patients had at least a 6-month survival. CONCLUSIONS: All 10 patients with Wilson's disease who underwent TPE had a positive outcome in terms of 6-month survival. In this first report of the ASFA apheresis registry study, we have demonstrated the value of using this registry to collect apheresis related patient outcomes from multiple centers. PMID- 26275241 TI - Mycelial Mattress from a Sporangia Formation-Delayed Mutant of Rhizopus stolonifer as Wound Healing-Enhancing Biomaterial. AB - A mycelial mattress of Rhizopus stolonifer obtained from a liquid static culture was utilized for wound dressing and biomedical use. Following screening of mutants induced by UV radiation, F6, exhibiting delayed sporangium formation was selected because its sporangium maturation exhibited a 5-day delay without significant loss of mycelial weight compared to the wild type. The sporangium free mycelial mattress from the sporangiospore culture of F6 was treated with 1N sodium hydroxide NaOH at 85 degrees C for 2 h to produce a sponge-like membrane named Rhizochitin. The trifluoroacetic acid hydrolysate of Rhizochitin contained 36% N-acetylglucosamine and 53% hexose respectively detected by the Elson-Morgen and phenol-sulfuric acid methods. Results indicated the wound area in rats covered with Rhizochitin was 40% less than that of the uncovered group. Rhizochitin decreased the expression of PDGF in the proliferation stage, increased the expression of TGF-beta in the inflammation and proliferation stages, and increased the expression of VEGF in the inflammation and proliferation stages. Rhizochitin inhibited secretion of matrix metalloproteinase 9 on days 1, 7, 9, and 12 and matrix metalloproteinase-2 on days 3, 7, 9, and 12. It was concluded that Rhizochitin has beneficial properties of biocompatible, biodegradable, and wound healing. PMID- 26275243 TI - Correction: Unravelling the Structural and Molecular Basis Responsible for the Anti-Biofilm Activity of Zosteric Acid. PMID- 26275242 TI - Reducing GBA2 Activity Ameliorates Neuropathology in Niemann-Pick Type C Mice. AB - The enzyme glucocerebrosidase (GBA) hydrolyses glucosylceramide (GlcCer) in lysosomes. Markedly reduced GBA activity is associated with severe manifestations of Gaucher disease including neurological involvement. Mutations in the GBA gene have recently also been identified as major genetic risk factor for Parkinsonism. Disturbed metabolism of GlcCer may therefore play a role in neuropathology. Besides lysosomal GBA, cells also contain a non-lysosomal glucosylceramidase (GBA2). Given that the two beta-glucosidases share substrates, we speculated that over-activity of GBA2 during severe GBA impairment might influence neuropathology. This hypothesis was studied in Niemann-Pick type C (Npc1-/-) mice showing secondary deficiency in GBA in various tissues. Here we report that GBA2 activity is indeed increased in the brain of Npc1-/- mice. We found that GBA2 is particularly abundant in Purkinje cells (PCs), one of the most affected neuronal populations in NPC disease. Inhibiting GBA2 in Npc1-/- mice with a brain permeable low nanomolar inhibitor significantly improved motor coordination and extended lifespan in the absence of correction in cholesterol and ganglioside abnormalities. This trend was recapitulated, although not to full extent, by introducing a genetic loss of GBA2 in Npc1-/- mice. Our findings point to GBA2 activity as therapeutic target in NPC. PMID- 26275244 TI - Changes at genetic and molecular level to identify the specific targets for selected therapy. PMID- 26275245 TI - Matrix metalloproteinase 7 expression in ampullary carcinoma. AB - BACKGROUND: Matrix metalloproteinase 7 (MMP7) has largely been studied in pancreatic cancer which is the most common component of periampullary cancer in the western population. In India, the ampullary carcinoma is seen as the most common periampullary cancer in resected pancreaticoduodenectomies. We aimed to study the expression of MMP7 and its correlation with clinicopathological features in ampullary cancer. MATERIALS AND METHODS: Consecutive cases of all ampullary cancer in a 3-year period were reviewed for histological differentiation (intestinal and pancreatobiliary) by morphology and immunohistochemistry (CDX2, MUC2, cytokeratin 20 [CK20], MUC1, cytokeratin 7 [CK7], and cytokeratin 17 [CK17]). All cases were stained for MMP7 and expression was correlated with histological variables, differentiation, and overall survival. RESULTS: There were a total of 91 ampullary carcinomas (36 intestinal, 44 pancreatobiliary and 6 other types). Ampullary carcinoma showed MMP7 expression in 63.7% cases. Two-third of intestinal type and half of the pancreatobiliary type cancers showed MMP7 expression. MMP7 expression was significantly higher in low pathological T-stage of total ampullary carcinomas; however, it was seen more commonly in higher overall stage of the pancreatobiliary type compared to intestinal type of ampullary carcinoma. Overall survival in patients with MMP7 expression was lower compared to MMP7 negative patients. CONCLUSIONS: This is the first study on MMP7 expression in ampullary cancer. MMP7 expression was seen in nearly 64 % of ampullary cancer and showed a significant correlation with low pathological (T-) stage and high overall stage with a shorter survival. MMP7 can be explored as a target for MMP inhibitor therapy in the future. PMID- 26275246 TI - BRAF, KIT, NRAS, GNAQ and GNA11 mutation analysis in cutaneous melanomas in Turkish population. AB - BACKGROUND: KIT and mitogen-activated protein kinase cascade are important for melanomagenesis. In the present study, we analyzed the frequency of BRAF, NRAS, KIT, GNAQ and GNA11 gene mutations and investigated their association with clinicopathological features of melanomas in Turkish population. MATERIALS AND METHODS: Forty-seven primary cutaneous melanomas were included in our study. Sanger sequencing method was used for mutation analysis in all cases. RESULTS: Mean age was 62.1 (29-101) years. Female:male ratio was 17:30. Among 47 melanomas, 14 (29.8%) BRAF, 10 (21.3%) NRAS, 4 (8.5%) KIT and 1(2.1%) GNAQ gene mutations were detected. Two of the KIT mutations were found in acral lentiginous melanoma (ALM). In the head and neck region, mutation frequency was significantly lower than in other locations (P = 0.035). The only GNAQ gene mutation (p.Q209L) was detected in a melanoma arising from blue nevus located on the scalp. None of the melanomas harbored NRAS exon 2, KIT exon 13/17/18, GNAQ exon 4 and GNA11 exon 4/5 mutations. Overall mutation frequency did not show significant difference between metastatic (8/14, 57.1%) and nonmetastatic (18/33, 54.5%) patients. We did not observe any significant association between mutation status and gender or age of various patients. CONCLUSIONS: Our results support that BRAF and NRAS gene mutations are common in cutaneous melanomas. The activating mutations of KIT gene are rare and especially seen in ALM. GNAQ and GNA11 mutations are infrequent in cutaneous melanomas and may be associated only with melanomas arising from blue nevus. PMID- 26275247 TI - Risk factors, organ weight deviation and associated anomalies in neural tube defects: A prospective fetal and perinatal autopsy series. AB - INTRODUCTION: Neural tube defects (NTD) are a group of serious birth defects occurring due to defective closure of neural tube during embryonic development. It comprises of anencephaly, encephalocele and spina bifida. We conducted this prospective fetal autopsy series to study the rate and distribution of NTD, analyze the reproductive factors and risk factors, note any associated anomalies and evaluate the organ weights and their deviation from normal. MATERIALS AND METHODS: This was a prospective study done over a period of 6 years from August, 2007 to July, 2013. All cases of NTDs delivered as abortion, still born and live born were included. The reproductive and risk factors like age, parity, multiple births, previous miscarriage, obesity, diabetes mellitus, socioeconomic status and use of folic acid during pregnancy were collected.Autopsy was performed according to Virchow's technique. Detail external and internal examination were carried out to detect any associated anomalies. Gross and microscopic examination of organs were done. RESULTS: Out of 210 cases of fetal and perinatal autopsy done, 72 (34.28%) had NTD constituting 49 cases of anencephaly, 16 spina bifida and 7 cases of encephalocele. The mothers in these cases predominantly were within 25-29 years (P = 0.02) and primy (P = 0.01). Female sex was more commonly affected than males (M:F = 25:47, P = 0.0005) There was no history of folate use in majority of cases. Organ weight deviations were >2 standard deviation low in most of the cases. Most common associated anomalies were adrenal hypoplasia and thymic hyperplasia. CONCLUSION: The authors have made an attempt to study NTD cases in respect to maternal reproductive and risk factors and their association with NTD along with the organ weight deviation and associated anomalies. This so far in our knowledge is an innovative study which was not found in literature even after extensive search. PMID- 26275248 TI - Solid-pseudopapillary neoplasm of the pancreas: Clinicopathologic and immunohistochemical analysis of nine cases. AB - BACKGROUND: Solid-pseudopapillary neoplasm (SPPN) of the pancreas is a distinctive tumor of low malignant potential with a predilection for female patients in the second and third decades of life. We studied nine cases of SPPN of the pancreas and reviewed the literature concerning these uncommon tumors. MATERIALS AND METHODS: A total of 7 cases of SPPN located in the tail of the pancreas and two located in the head of the pancreas were presented. Distal pancreatectomy in three patients and distal pancreatectomy with splenectomy in two patients Whipple's operation in four patients were performed. Histological diagnosis was made by performing hematoxylin-eosin and periodic acid-Schiff staining, immunohistochemical staining. Follow-up of the patients was between 2 months and 12 years. RESULTS: Computed tomography and magnetic resonance imaging were found as equivocal for diagnosis. Mass containing cystic and solid areas were not characteristic but raised suspicion of SPPN. Pathologic examination showed SPPN in all patients. No metastasis or recurrence was detected during follow-up. CONCLUSIONS: Solid-pseudopapillary neoplasm is a relatively rare tumor, and patients tend to survive for a long period. Preoperative imaging is not characteristic. Pathologic examination is the mainstay in the diagnosis. Complete surgical removal is the best choice of treatment. PMID- 26275249 TI - Primary extranodal non-Hodgkin lymphoma: A 3-year record-based descriptive study from a tertiary care center in Southern India. AB - INTRODUCTION: Primary extranodal lymphoma (pENL) refers to group of disorders arising from tissues other than lymph nodes and even from sites, which normally do not contain lymphoid tissue. This study was undertaken to ascertain the prevalence, anatomical distribution, and histological subtypes of extranodal non Hodgkin lymphoma (NHL) from a tertiary care institute in Southern India. MATERIALS AND METHODS: This was a cross-sectional study conducted in the Department of Pathology over a period of 3-years. Detailed clinical history, routine complete blood count, microbiological status was obtained from the medical records. Hamatoxylin and eosin slides were reviewed and immunohistochemistry was performed using a panel of antibodies depending on the morphology. All cases were classified based upon morphologic and immunophenotypic criteria according to World Health Organization 2008 classification. RESULTS: Primary extranodal NHL constituting 22.6% (68/300) of all NHL and the majority of patients were from higher age group with peak incidence seen in fourth to fifth decade of life. In the pediatric population, the most common site is ileo-caecal region (42.8%) and the most common morphology is lymphoblastic lymphoma (42.8%). Similarly in the adult population head and neck was the most common site constituting 36% and diffuse large B-cell lymphoma is the most common morphological subtype comprising 54% of all extranodal lymphomas. CONCLUSION: Although the reported incidence of pENL is low in India compared to other parts of the world, the possibility of pENL should always be kept in mind even though it arises in an extranodal site. PMID- 26275250 TI - Malignant transformation of mature T cells after gammaretrovirus mediated transfer of nucleophosmin-anaplastic lymphoma kinase oncogene. AB - BACKGROUND: Gene therapy has been in use to cure hereditary and acquired diseases by incorporating the desired gene into the cells with the help of gammaretroviral vectors. Despite the success of this therapy in X-linked severe combined immunodeficiency syndrome, few patients developed leukemia as a major adverse event due to retroviral insertional mutagenesis within stem cells. In experimental animals also, retroviral-mediated gene transfer technique resulted in the development of leukemia. On the other hand, evidence suggests that mature T cells (TC) are relatively resistant to transformation even after retroviral mediated transfer of potent oncogenes Tcl1, DeltaTrkA and LMO2 with no reported side effects yet. AIMS: To further address the safety issue for TC use in gene therapy, this study investigated susceptibility of mature polyclonal TC to malignant transformation by the retroviral-mediated transfer of nucleophosmin anaplastic lymphoma kinase (NPM-ALK) oncogene. MATERIALS AND METHODS: Wild-type mature TC, isolated from C57BL/6 donor mice (genetic background Ly5.1) were transduced with gamma-retroviral vectors encoding the potent TC oncogene NPM-ALK or the control vector enhanced green fluorescent protein eGFP. The cells were then transplanted into RAG-1 deficient recipient mice (genetic background Ly5.2). RESULTS: Two out of five mice from NPM-ALK oncogene group developed leukemia/lymphoma after latency periods (153 and 250 days, respectively). None of the mice from the control group developed any malignancy throughout the observational period. CONCLUSION: Mature polyclonal TC are relatively susceptible to malignant transformation after gamma-retroviral mediated transfer of NPM-ALK oncogene; hence safety of TC use in gene therapy should be further investigated to avoid the possible side-effect of development of leukemia/lymphoma. PMID- 26275252 TI - Sehgal index: A new index and its comparison with other complete blood count based indices for screening of beta thalassemia trait in a tertiary care hospital. AB - INTRODUCTION: Beta thalassemia trait (BTT) must be differentiated from iron deficiency anemia to avoid unnecessary iron therapy and for the prevention of thalassemia major by genetic counseling. In a tertiary care hospital, it is vital that the screening tool is not only sensitive but also specific so as to be cost effective and save time. AIM: The aim of this study was to evaluate the new Sehgal index and compare it to existing complete blood count-based indices for the best combination of sensitivity and specificity to predict BTT. MATERIALS AND METHODS: Study was done in 2 phases - Phase 1: A retrospective analysis of 1022 consecutive high-performance liquid chromatography (HPLC) cases from July 2008 to June 2011. Phase 2: A prospective analysis of 973 consecutive HPLC cases from July 1, 2011 to June 10, 2013 was done to confirm the results of Phase 1 and the applicability of the new Sehgal index. RESULTS: Prevalence of BTT was 28.8% (294/1022) and 25.39% (247/973) in Phase 1 and Phase 2, respectively. Receiver operating characteristic-area under the curve and Youden index was highest for new Sehgal index, followed by Mentzers index <14. The prospective study shows results similar to those in Phase 1 confirming the superiority of the above two indices. CONCLUSION: Sehgal index and Mentzers index <14 showed the best combination of sensitivity and specificity in predicting BTT. The best indices or combination can be used as a "validated flag rule" in the analyzer middleware program in a hospital for identifying suspected cases of BTT. PMID- 26275251 TI - Mean reticulocyte volume enhances the utility of red cell mean sphered cell volume in differentiating peripheral blood spherocytes of hereditary spherocytosis from other causes. AB - CONTEXT: Mean sphered cell volume (MSCV) and mean reticulocyte volume (MRV) are additional reticulocyte parameters generated while processing the blood samples on Beckman coulter LH 755 in the reticulocyte mode using the volume, conductivity and scatter technology. It has been observed that the difference between mean corpuscular volume (MCV) and MSCV is higher in the cases of hereditary spherocytosis (HS) and this difference is increasingly being utilized as a screening tool for spherocytes. In addition now there have been new observations that reticulocyte volume in cases of HS is less as compared to normal reticulocyte. AIMS: Our aim was to test the usefulness of reticulocyte parameters like MSCV and MRV in distinguishing cases of HS and autoimmune hemolytic anemia (AIHA). MATERIALS AND METHODS: This is a retrospective and partly prospective study where peripheral blood ethylenediaminetetraacetic acid samples from cases of HS (n = 57) and AIHA (n = 29) were processed on LH 755 in both the differential and the reticulocyte mode. The data generated were analyzed and compared with data from normal healthy donors (n = 46). RESULTS: Using an algorithm of MCV - MSCV >10 and MRV - MSCV <25, a sensitivity of 84.2% and specificity of 94.7% was observed in cases of HS. CONCLUSIONS: With the reticulocyte analysis, we may now have a simple and cheap additional tool for screening of HS. PMID- 26275253 TI - Accelerated staining technique using kitchen microwave oven. AB - INTRODUCTION: Histopathological diagnosis of specimens is greatly dependent on good sample preparation and staining. Both of these processes is governed by diffusion of fluids and dyes in and out of the tissue, which is the key to staining. Diffusion of fluids can be accelerated by the application of heat that reduces the time of staining from hours to the minute. We modified an inexpensive model of kitchen microwave oven for staining. This study is an attempt to compare the reliability of this modified technique against the tested technique of routine staining so as to establish the kitchen microwave oven as a valuable diagnostic tool. MATERIALS AND METHODS: Sixty different tissue blocks were used to prepare 20 pairs of slides for 4 different stains namely hematoxylin and eosin, Van Gieson's, 0.1% toluidine blue and periodic acid-Schiff. From each tissue block, two bits of tissues were mounted on two different slides. One slide was stained routinely, and the other stained inside a microwave. A pathologist evaluated the stained slides and the results so obtained were analyzed statistically. RESULTS: Microwave staining considerably cut down the staining time from hours to seconds. Microwave staining showed no loss of cellular and nuclear details, uniform-staining characteristics and was of excellent quality. INTERPRETATION AND CONCLUSION: The cellular details, nuclear details and staining characteristics of microwave stained tissues were better than or equal to the routine stained tissue. The overall quality of microwave-stained sections was found to be better than the routine stained tissue in majority of cases. PMID- 26275254 TI - Molecular characterization and clinical significance of New Delhi metallo-beta lactamases-1 producing Escherichia coli recovered from a South Indian tertiary care hospital. AB - CONTEXT: The increased rate of infection by New Delhi metallo-beta-lactamases-1 (NDM1) producing Escherichia coli is a major concern since they show a high rate of drug resistance and are responsible for mortality and morbidity. AIMS: To characterize the NDM1 producing E. coli isolates and their impact on patients' clinical outcome. SETTINGS AND DESIGN: This descriptive study was carried out in a multi-specialty tertiary care hospital. MATERIALS AND METHODS: Three hundred nonrepeat strains of E. coli from inpatients were included in the study. Modified Hodge test and metallo-beta-lactamases (MBL) e-test were performed to detect carbapenemase and MBL activity. Polymerase chain reaction (PCR) technique was performed to detect NDM1. NDM1 positive isolates were further tested for plasmid mediated AmpC, blaCTX , blaSHV , blaTEM genes and also for phylogrouping by PCR methods. Treatment and patients' clinical outcome were also analyzed. RESULTS: Out of 300 isolates, 21 (7%) were MBL producers by phenotypic methods. Of this, 17 (81%) were NDM1 positives, among the NDM1 producers 6 (35%) isolates were belongs to phylogroups D followed by A 5 (29%), B1 4 (24%) and B2 2 (12%), 15 (88%) isolates were blaCTX-M positive suggestive of extended-spectrum beta lactamase producing strain and 7 (47%) were positive with CIT type of AmpC. With the follow-up of the patients, it was found that 12 (71%) recovered and 3 (18%) developed relapses, and mortality was seen in 2 (12%) patients. CONCLUSIONS: NDM1 producing isolates showed a high degree of drug resistance but can be treated with suitable antimicrobials, in the majority. Early detection and choice of appropriate antibiotics may help in reducing mortality and morbidity. PMID- 26275255 TI - Dengue virus infection: Need for appropriate laboratory tests for diagnosis and management of the condition in children during an outbreak. AB - BACKGROUND: Outbreaks of dengue infection occur in several parts of India with clockwork precision closely related to changing seasons. Most recent outbreak in Puducherry occurred between October 2012 and January 2013, affected a sizable pediatric population. A prospective study was done to characterize the demographic, diagnostic and clinical profile of pediatric patients in a tertiary care center in Puducherry. MATERIALS AND METHODS: Data of patients serologically positive for either dengue NS1 antigen or anti-dengue IgM antibodies were analyzed. Duration of fever, platelet count, complications, risk factors, morbidity and mortality were analyzed. RESULTS: Among pediatric cases with fever who were screened for NS1/IgM antibody during the recent outbreak, 161 (37.5%) tested positive. NS1 was detected in 85% while 5.5% tested positive for IgM and 3% for IgG. Few (4.9%) tested positive for both NS1 and IgM and 1.2% were positive for both NS1 and IgG. The mean age was 6 years of which 9% were <1-year, the youngest being 1-month old infant. Mean duration of fever was 4 days. Vomiting was associated in 42% of cases. Thrombocytopenia (51%) and hepatomegaly (41%) were two major observations. Among the NS1 positive cases, 49% had thrombocytopenia. IgM alone and NS1 with IgM were associated with thrombocytopenia in 67% and 78% respectively. 14 children had complications of dengue shock syndrome, and four had dengue hemorrhagic fever. Totally, 22 of the children had platelet transfusion. There was no mortality reported among any of these children. CONCLUSION: Combination of clinical findings and rapid NS1, IgM detection helped in confirming the diagnosis for appropriate management of dengue in children. PMID- 26275256 TI - Subconjunctival dirofilariasis caused by Dirofilaria repens: A case report with short review. AB - Human dirofilariasis is a rare infection caused by filarial worms of genus Dirofilaria. Subconjunctival dirofilariasis has been reported from Asia, Europe, Italy and Africa. In India majority cases are from Kerala, Karnataka and very few from Maharashtra. We report the rare case of subconjunctival dirofilariasis caused by Dirofilaria repens from Maharashtra, western India. PMID- 26275257 TI - Sclerosing rhabdomyosarcoma presenting on the knee-joint. AB - Sclerosing rhabdomyosarcoma is a rare pathological diagnosis that easily misdiagnosed. The majority of cases reported the tumor increased rapidly in size and the Ki-67 proliferation index ranged from 10% to 60%. Here, we report the first case of the tumor increased very slowly for 20 years and the Ki-67 proliferation index was lower than 2%, and discuss its histological features and immunohistochemical reactivity with Desmin and Ki-67 and so on. PMID- 26275258 TI - Primary pulmonary leiomyosarcoma of lung: An unusual entity with brief review. AB - Primary pulmonary leiomyosarcomas are rare and diagnostically challenging group of neoplasms approximately constituting 0.2-0.5% of all primary lung malignancies. They originate from the smooth muscle cells of the bronchial wall, blood vessels or from the pulmonary interstitium. Here we present a case of 45 year old male with history of chronic cough, breathlessness and chest pain for few months. Clinical and radiological workup showed a left upper lobe lung mass. Endobronchial ultrasound guided (EUS) needle biopsy of the mass on histopathology confirmed leiomyosarcoma. Further through evaluation ruled out the possibility of metastasis. A final diagnosis of primary leiomyosarcoma of lung was made and patient was planned for surgical management. PMID- 26275259 TI - Primary Ewing sarcoma of vulva, confirmed with molecular cytogenetic analysis: A rare case report with diagnostic and treatment implications. AB - Primary vulvar Ewing sarcoma (ES)/PNET is an uncommonly documented tumor, especially with molecular results. A 10-year-old girl presented with left vulvar swelling, a year ago. Her abdominopelvic ultrasound revealed a 12 cm * 8 cm sized, mixed echogenic blood-filled lesion in the left vulva; radiologically considered as a hematoma. Vulvectomy revealed a multinodular grey-brown tumor, microscopically comprising malignant round cells. Immunohistochemically, tumor cells diffusely expressed MIC2/CD99 and Fli1 and subsequently displayed EWSR1 rearrangement, confirming diagnosis of ES/PNET. Subsequently, PET-CT scan revealed residual local lesion with lung metastases. The patient was induced on EFT 2001 chemotherapy protocol. Three months after chemotherapy completion, there was no metabolically active disease on PET scan. Four months later, MRI disclosed recurrent primary and metastatic pulmonary lesions. She was planned for scar excision and adjuvant radiotherapy, but unfortunately defaulted further treatment. This forms the eighth case of primary vulvar ES/PNET confirmed with molecular cytogenetic result, underscoring therapeutic value of objective diagnosis in such cases. PMID- 26275260 TI - Primary cardiac sarcoma with metastases to thyroid and brain. AB - Primary cardiac sarcomas are extremely rare with only a few large case series and isolated case reports in the literature. In spite of their aggressive nature with high chances of local recurrence and distant metastases, these tumors and their treatment strategies remain incompletely defined. We report an unsuspected case of primary cardiac pleomorphic undifferentiated sarcoma in a 52-year-old female who presented with progressive dyspnea and palpitation. In the postoperative period, she was detected to have secondaries in brain and thyroid, confirmed thereafter, by fine-needle aspiration cytology. PMID- 26275261 TI - Diffuse lipomatosis of the thyroid gland with papillary microcarcinoma: Report of a rare entity. AB - Presence of lobules of adipose tissue either focally or diffusely is very rare in the thyroid gland. Fat accumulation can be macroscopic or microscopic. Focal infiltrates of fat have been reported in conditions such as adenolipoma, intrathyroid lipoma, and encapsulated papillary carcinoma. Diffuse lipomatosis has been reported in conditions such as amyloid goitre, heterotopic fat nests, thyrolipoma and liposarcoma. The exact mechanism of fat accumulation is not known although there are many theories postulated. Investigations such as ultrasound, computed tomography scan, and magnetic resonance imaging can detect the presence of macroscopic fat in the thyroid gland. Accurate diagnosis of the type of fat accumulation is necessary because tumorous and nontumorous conditions fall into the differential diagnosis. Only nine cases of papillary carcinoma associated with lipomatosis of thyroid are reported so far. We report possibly the first case of diffuse lipomatosis of the thyroid gland with a focus of papillary microcarcinoma. PMID- 26275262 TI - Large lipid-rich mammary analogue secretory carcinoma of parotid gland: An unusual case. AB - Mammary analogue secretory carcinoma (MASC) of the salivary gland is a malignant tumor which bears morphologic, immunohistochemical and molecular features similar to those of mammary secretory carcinoma. The tumor is considered as a low-grade malignancy perhaps slightly more aggressive than acinic cell carcinoma. High grade transformation with recurrences, regional nodal involvement, metastases, and cancer-related death has been reported in a few cases. We report an unusual case of large MASC of the parotid gland in a young patient without regional lymph node involvement. To the best of our knowledge till date such a large MASC of the salivary gland has not been reported in the English literature. PMID- 26275263 TI - Clear cell renal cell carcinoma with hemangioblastoma-like features: A recently described pattern with unusual immunohistochemical profile. AB - The diagnosis of clear cell renal cell carcinoma may sometimes pose challenges because of the presence of uncharacteristic morphology, varied immunophenotypic patterns and due to lack of molecular or genetic determinants. More often, the morphological variations can be easily overlooked in routine practice and a more common diagnosis is usually put forward. Solid, acinar and alveolar are the common patterns described in the literature. We report a recently described pattern of clear cell renal cell carcinoma which has hemangioblastoma-like morphology and an unusual immunoprofile. In our case, the tumor showed a diffuse hemangioblastoma-like pattern and diffuse positivity for Alpha-inhibin on immunohistochemistry. A thorough literature search, extensive sampling and an expanded immunohistochemistry panel revealed a clear cell renal cell carcinoma component. Presence of renal vein thrombosis and focal necrosis were other helpful features in discerning the malignant nature of tumor. PMID- 26275264 TI - Bilateral pseudoangiomatous stromal hyperplasia in a human immunodeficiency viral infected patient. AB - Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon mesenchymal neoplasm of the breast demonstrating stromal myofibroblastic proliferation and having the appearance of anastomosing slit-like pseudovascular spaces lined by spindle shaped cells. A case of nodular PASH of the bilateral breasts in a 40-year-old woman with clinically presenting with a progressive enlarged breast lump is reported. Mammographic and ultrasonographic features of the right and left breasts showed a large solid lump with well-circumscribed border measuring 4 cm * 1.7 cm * 3.4 cm and 13.8 cm * 10.9 cm * 12.1 cm, respectively. Wide excision of the right breast and quadrantectomy of the left breast were performed. The histopathological examination of the lesion showed anastomosing slit-like pseudovascular spaces. The stromal cells were immunoreactive for muscle actin (HHF35), smooth muscle actin, and progesterone receptor. Clinical and pathological findings with briefly reviewed relevant literatures are discussed. This is the first clinicopathological and radiological report of bilateral mammary nodular PASH in a human immunodeficiency viral-infected patient. PMID- 26275265 TI - Sclerosing angiomatoid nodular transformation of spleen masquerading as a splenic abscess. AB - Here we report an incidental case of sclerosing angiomatoid nodular transformation (SANT) in an open splenectomy specimen from a young man who presented with insidious abdominal pain. The condition was mimicking as a splenic abscess. Histopathological and immunohistochemical analysis confirmed this to be SANT. SANT presents a diagnostic challenge to clinicians, radiologists, as well as pathologists because of its extreme rarity. Therefore, it must be included as a differential diagnosis in cases with nonspecific pain or radiological splenic mass. This case highlights that SANT can present with varied clinical features and at a wide range of ages. A high index of suspicion is required for its diagnosis. PMID- 26275266 TI - Sarcoidosis detected due to tattoo swellings in an Indian female. AB - A female patient presented with asymptomatic swellings in old blue-black tattoo marks of her forearms. On careful skin examination, few raised erythematous, circular plaques were also found on the non-tattooed skin on her back, about which she was unaware. The diagnosis of cutaneous and systemic sarcoidosis was confirmed after classical histopathological findings from skin lesions from her non tattooed back and from papulonodular tattooed lesions, ruling out other causes of granulomas and supported by a negative Mantoux test, raised serum angiotensin converting enzyme level, high resolution computed tomography thorax, etc. She responded well to oral steroid therapy. The importance of a careful skin examination, easy access provided by skin lesions in suspected cases of cutaneous/systemic sarcoidosis, the value of sudden tattoo changes in the diagnosis here and the possible contribution of tattoos toward the causation of cutaneous and/or systemic sarcoidosis are highlighted. PMID- 26275267 TI - Solid-pseudopapillary neoplasm of the pancreas: A classical presentation with unique paranuclear dot like immunostaining with CD 99. AB - A 32-year-old lady presented with a history of abdominal pain and upper abdominal discomfort of 3 months duration. Her imaging studies done at a local hospital showed a solid-cystic mass involving head of the pancreas. The patient was referred to our surgical oncology department. On examination, there was a nontender mass in the epigastrium. An ultrasound scan guided fine-needle aspiration (FNA) was done which was showing classical features of solid-pseudo papillary neoplasm of the pancreas. With this preoperative diagnosis patient was taken up for surgery. Per operatively, there was a solid-cystic mass in the head of the pancreas. Pancreaticoduodenectomy was done. Histopathology and immunohistochemistry (IHC) confirmed the diagnosis of solid-pseudo papillary neoplasm of the pancreas. Apart from the routine IHC panel, CD 99 immunostain was also done which demonstrated the characteristic paranuclear dot-like staining observed in previous studies in the literature. PMID- 26275268 TI - Psammomatous melanotic schwannoma as a component of Carney complex. AB - Melanotic schwannoma is a rare form of pigmented neural tumor commonly arising from the posterior spinal nerves and ganglia. Two variants have been described, psammomatous and nonpsammomatous. 50% of psammomatous tumors are associated with Carney complex. The biologic behavior of the tumor is difficult to predict and slightly over 10% of the tumors follow malignant course. We present a case of psammomatous melanotic schwannoma as part of Carney complex in a 67-year-old male. Clinical examination revealed oral mucosal and abdominal skin pigmentation. Magnetic resonance imaging showed an intradural extramedullary lesion at D8-D12 level. Intraoperative squash smear study showed sheets of spindle cells with abundant intracytoplasmic melanin pigmentation and few psammoma bodies. Based on clinical, radiologic, and histopathological findings with immunohistochemistry correlation a final diagnosis of psammomatous melanotic schwannoma was rendered. PMID- 26275270 TI - Acute postinfectious glomerulonephritis with a large number of crescents caused by Mycoplasma pneumoniae. AB - Mycoplasma pneumoniae-induced acute postinfectious glomerulonephritis has various pathological changes and relatively poor prognosis. It often occurs in children, barely in adults. Currently, no clear treatment guidelines have been established for its treatment using glucocorticoid and immunosuppressive. In this study, we report an adult who admitted to our hospital due to fever and gross hematuria. The patient presented with nephritic syndrome and renal failure and confirmed to have M. pneumoniae infection by serum detection and acute postinfectious glomerulonephritis with a large number of crescents by renal biopsy. He was given glucocorticoid, immunosuppressive agent combined with hemodialysis as well as other supportive treatment. Three months later, his renal function became normal, urine protein level decreased to 0.4 g/24 h, and the C3 complement increased to normal level. In conclusion, glucocorticoid and immunosuppressive treatment should be given to patients with M. pneumoniae-infection induced glomerulonephritis after confirmed to have a large number of crescents by renal biopsy and the treatment could improve the prognosis. PMID- 26275269 TI - Mesenchymal dysplasia of placenta. AB - A rare case of placental mesenchymal dysplasia (PMD) in a 26-year-old patient is reported. Ultrasound scan at 17 weeks of gestation showed placenta with multiple cystic spaces and a normal appearing fetus. Following delivery of a term live baby, histological examination of the placenta was suggestive of PMD. The early recognition of this rare condition by characteristic ultrasonographic findings is herein emphasized and hence that PMD is distinguished from molar pregnancy. PMID- 26275271 TI - Blastic plasmacytoid dendritic cell neoplasm presenting as leukemia without cutaneous involvement in a 25 years male patient: Unusual presentation of a rare entity. AB - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive neoplasm classified under "acute myeloid leukemia (AML) and related precursor neoplasm" by current WHO classification. Elderly male are commonly affected with cutaneous lesion being the hallmark of disease presentation. The disease progresses rapidly and sooner or later involves bone marrow and peripheral blood. Cases presenting primarily as leukemia without cutaneous involvement is a rarity with about 29 cases reported in literature till date. Characteristic immunophenotype of CD4 + /CD56 +/- cells expressing antigens associated with plasmacytoid dendritic cells like CD123, TCL1, BDCA2/CD303, cutaneous lymphocyte associated and interferon dependent molecule MxA, in absence of any other lineage specific marker confirms the diagnosis. The disease has a poor survival and no standardized therapeutic strategy in the current scenario. A case of 25-year-male presenting with leukemic BPDCN without cutaneous involvement is presented here, who was treated with AML like protocol followed by hematopoietic stem cell transplantation, but succumbed to the disease within 8 months of diagnosis. The present case is being first to be reported from India. PMID- 26275272 TI - Early onset mixed cryoglobulinemia in hepatitis C. AB - Cryoglobulinemia is one of the most common forms of extrahepatic manifestation of chronic hepatitis infection. The phenomenon is generally seen after several years of chronicity predominantly in the female population resulting in arthralgias, purpuras, and other symptoms, due to vasculitis. Here we present a case of incomplete mixed cryoglobulinemia Type III (as per Brouet's classification) in a young boy aged 13 years who presented with an unusual symptom of pruritus. Diagnosis was confirmed by cryoprecipitation test followed by immunofixation. We aim to highlight the difficulty in diagnosis of this rare case/presentation, important investigation pitfalls and how to avoid them. PMID- 26275273 TI - Brevundimonas diminuta bacteremia in a man with myelodysplastic syndromes. AB - Brevundimonas diminuta are ubiquitous in the environment, but are infrequently isolated from clinical samples. Here we report a case of B. diminuta bacteremia in a man with myelodysplastic syndromes (MDS) at a teaching hospital in China and review the previously reported cases. The organism was confirmed by culture and 16s rRNA sequence analysis with highly sensitivity to broad-spectrum antibiotics. Our report and other cases demonstrated that the optimal therapeutic duration for B. diminuta infections in various situations remains to be established. PMID- 26275274 TI - Subcutaneous human Dirofilariasis in Vidarbha. AB - Zoonotic filariasis due to Dirofilaria repens is prevalent in several regions of the world. Human dirofilariasis due to D. repens has not been widely recognized in India, but few cases reported from some parts of India. Dirofilaria species are commonly encountered in the subcutaneous tissue of dogs, foxes, and cats and it can accidentally infect humans. Here, we report a case of subcutaneous dirofilariasis, presenting as a subcutaneous nodule on the right leg of a 25-year old female from Vidarbha region. PMID- 26275275 TI - Cervical strongyloidiasis in an immunocompetent patient: A clinical surprise. AB - A 32-year-old lady came for a routine gynecological check up. Her cervical cytologic smear was reported as low grade squamous intraepithelial lesion. As a part of basic routine investigation, cervical punch biopsy was done. Astonishingly it revealed multiple rhabditiform larvae of Strongyloides stercoralis. These were curved thick with pointed end and a short buccal cavity. She did not have any history of immunosuppression including steroid therapy and was otherwise normal. Extensive review of the literature on parasites encountered in cervix yielded few case reports on strongyloides in cytologic smears, but failed to reveal any report till date on S. stercoralis found in histopathology section. Our case is probably the first in the world and the first reported from India to the best of our knowledge. We describe this case of strongyloidiasis of cervix with review of the literature on various parasites encountered in the cervix because of its rarity and also to keep this parasitic infestation as a differential diagnosis of cervical lesions. PMID- 26275276 TI - Chlamydia pneumoniae-related hemophagocytic lymphohistiocytosis in an adult patient with clonal karyotype abnormality. AB - Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease characterized by a severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages. Herein, we report a 58-year-old male who had Chlamydia pneumoniae-related pneumonia, followed by aggressive HLH. An abnormal cytogenetic profile was also detected. To our knowledge, this is the first report of an adult patient with C. pneumonia-associated HLH. PMID- 26275277 TI - Uncommon pathogen: Serious manifestation: A rare case of Achromobacter xylosoxidans septic arthritis in immunocompetetant patient. AB - Achromobacter xylosoxidans is a rare opportunistic Gram-negative bacilli and rarer etiology of septic arthritis. We present here the first Indian case of septic arthritis due to A. xylosoxidans in 11-month-old male child confirmed by 16S rRNA sequencing. The child was admitted as suspected case of septic arthritis and underwent arthrotomy. Drained pus revealed Gram-negative bacilli, identified as Serratia odorifera by API (bioMerieux, Marcy l'Iotatoile, France), later subjected to VITEK 2 (bioMerieux, Marcy l'Iotatoile, France) identification revealing it to be A. xylosoxidans. It being a rare etiology of septic arthritis confirmation was done with 16S rRNA Sequencing. PMID- 26275278 TI - Atypical presentation of Whipple disease with no diarrhea. PMID- 26275279 TI - Myiasis in vulvar carcinoma in a patient with acquired immune deficiency syndrome. PMID- 26275281 TI - Vibrant colors of uric acid crystals on polarization. PMID- 26275280 TI - Rhinofacial entomophthoramycosis: A rare fungal infection in an adolescent boy. PMID- 26275282 TI - Subcutaneous infection by Cladosporium sphaerospermum-A rare case report. PMID- 26275283 TI - Sebaceous carcinoma. PMID- 26275284 TI - The myofibroblastic sarcoma of retroperitoneum: A diagnostic dilemma. PMID- 26275285 TI - Is histopathology informative for further characterization of DOTANOC-proven islet cell lesions in infancy? PMID- 26275286 TI - Primary diffuse large B-cell lymphoma of the central nervous system in pineal gland: Report of a rare case with review of literature. PMID- 26275287 TI - Trichosporon asahii as a cause of urinary tract infection: A rare human pathogen. PMID- 26275288 TI - Remembering Prof. K. C. Das. PMID- 26275290 TI - Empirical Evidence for Species-Specific Export of Fish Naivete from a No-Take Marine Protected Area in a Coastal Recreational Hook and Line Fishery. AB - No-take marine protected areas (MPAs) are assumed to enhance fisheries catch via the "spillover" effect, where biomass is exported to adjacent exploited areas. Recent studies in spearfishing fisheries suggest that the spillover of gear-naive individuals from protected to unprotected sites increases catch rates outside the boundaries of MPAs. Whether this is a widespread phenomenon that also holds for other gear types and species is unknown. In this study, we tested if the distance to a Mediterranean MPA predicted the degree of vulnerability to hook and line in four small-bodied coastal fish species. With the assistance of underwater video recording, we investigated the interaction effect of the distance to the boundary of an MPA and species type relative to the latency time to ingest a natural bait, which was considered as a surrogate of fish naivete or vulnerability to fishing. Vulnerability to angling increased (i.e., latency time decreased) within and near the boundary of an MPA for an intrinsically highly catchable species (Serranus scriba), while it remained constant for an intrinsically uncatchable control species (Chromis chromis). While all of the individuals of S. scriba observed within the MPA and surrounding areas were in essence captured by angling gear, only one fifth of individuals in the far locations were captured. This supports the potential for the spillover of gear-naive and consequently more vulnerable fish from no-take MPAs. Two other species initially characterized as intermediately catchable (Coris julis and Diplodus annularis) also had a shorter latency time in the vicinity of an MPA, but for these two cases the trend was not statistically significant. Overall, our results suggest that an MPA-induced naivete effect may not be universal and may be confined to only intrinsically highly catchable fish species. This fact emphasizes the importance of considering the behavioural dimension when predicting the outcomes of MPAs, otherwise the effective contribution may be smaller than predicted for certain highly catchable species such as S. scriba. PMID- 26275289 TI - Curation of the Mammalian Palmitoylome Indicates a Pivotal Role for Palmitoylation in Diseases and Disorders of the Nervous System and Cancers. AB - Palmitoylation involves the reversible posttranslational addition of palmitate to cysteines and promotes membrane binding and subcellular localization. Recent advancements in the detection and identification of palmitoylated proteins have led to multiple palmitoylation proteomics studies but these datasets are contained within large supplemental tables, making downstream analysis and data mining time-consuming and difficult. Consequently, we curated the data from 15 palmitoylation proteomics studies into one compendium containing 1,838 genes encoding palmitoylated proteins; representing approximately 10% of the genome. Enrichment analysis revealed highly significant enrichments for Gene Ontology biological processes, pathway maps, and process networks related to the nervous system. Strikingly, 41% of synaptic genes encode a palmitoylated protein in the compendium. The top disease associations included cancers and diseases and disorders of the nervous system, with Schizophrenia, HD, and pancreatic ductal carcinoma among the top five, suggesting that aberrant palmitoylation may play a pivotal role in the balance of cell death and survival. This compendium provides a much-needed resource for cell biologists and the palmitoylation field, providing new perspectives for cancer and neurodegeneration. PMID- 26275291 TI - Pathogenic Yersinia Promotes Its Survival by Creating an Acidic Fluid-Accessible Compartment on the Macrophage Surface. AB - Microbial pathogens and host immune cells each initiate events following their interaction in an attempt to drive the outcome to their respective advantage. Here we show that the bacterial pathogen Yersinia pseudotuberculosis sustains itself on the surface of a macrophage by forming acidic fluid-accessible compartments that are partially bounded by the host cell plasma membrane. These Yersinia-containing acidic compartments (YACs) are bereft of the early endosomal marker EEA1 and the lysosomal antigen LAMP1 and readily form on primary macrophages as well as macrophage-like cell lines. YAC formation requires the presence of the Yersinia virulence plasmid which encodes a type III secretion system. Unexpectedly, we found that the initial formation of YACs did not require translocation of the type III effectors into the host cell cytosol; however, the duration of YACs was markedly greater in infections using translocation-competent Y. pseudotuberculosis strains as well as strains expressing the effector YopJ. Furthermore, it was in this translocation- and YopJ-dependent phase of infection that the acidic environment was critical for Y. pseudotuberculosis survival during its interaction with macrophages. Our findings indicate that during its extracellular phase of infection Y. pseudotuberculosis initiates and then, by a separate mechanism, stabilizes the formation of a highly intricate structure on the surface of the macrophage that is disengaged from the endocytic pathway. PMID- 26275294 TI - A Novel Classification Algorithm Based on Incremental Semi-Supervised Support Vector Machine. AB - For current computational intelligence techniques, a major challenge is how to learn new concepts in changing environment. Traditional learning schemes could not adequately address this problem due to a lack of dynamic data selection mechanism. In this paper, inspired by human learning process, a novel classification algorithm based on incremental semi-supervised support vector machine (SVM) is proposed. Through the analysis of prediction confidence of samples and data distribution in a changing environment, a "soft-start" approach, a data selection mechanism and a data cleaning mechanism are designed, which complete the construction of our incremental semi-supervised learning system. Noticeably, with the ingenious design procedure of our proposed algorithm, the computation complexity is reduced effectively. In addition, for the possible appearance of some new labeled samples in the learning process, a detailed analysis is also carried out. The results show that our algorithm does not rely on the model of sample distribution, has an extremely low rate of introducing wrong semi-labeled samples and can effectively make use of the unlabeled samples to enrich the knowledge system of classifier and improve the accuracy rate. Moreover, our method also has outstanding generalization performance and the ability to overcome the concept drift in a changing environment. PMID- 26275292 TI - Does the Chemotherapy Backbone Impact on the Efficacy of Targeted Agents in Metastatic Colorectal Cancer? A Systematic Review and Meta-Analysis of the Literature. AB - IMPORTANCE: The EGFR inhibitors (EGFR-I) cetuximab and panitumumab and the angiogenesis inhibitors (AIs) bevacizumab and aflibercept have demonstrated varying efficacy in mCRC. OBJECTIVE: To document the overall impact of specific chemotherapy regimens on the efficacy of targeted agents in treating patients with mCRC. DATA SOURCES: MEDLINE, EMBASE and Cochrane databases were searched to 2014, supplemented by hand-searching ASCO/ESMO conference abstracts. STUDY SELECTION: Published RCTs of patients with histologically confirmed mCRC were included if they investigated either 1) chemotherapy with or without a biological agent or 2) different chemotherapy regimens with the same biological agent. EGFR I trials were restricted to KRAS exon 2 wild-type (WT) populations. DATA EXTRACTION AND SYNTHESIS: Data were independently abstracted by two authors and trial quality assessed according to Cochrane criteria. The primary outcome was overall survival with secondary endpoints progression free survival (PFS), overall response rate (ORR) and toxicity. RESULTS: EGFR-I added to irinotecan based chemotherapy modestly improved OS with HR 0.90 (95% CI 0.81-1.00, p = 0.04), but more so PFS with HR 0.77 (95% CI 0.69-0.86, p<0.00001). No benefit was evident for EGFR-I added to oxaliplatin-based chemotherapy (OS HR 0.97 (95% CI 0.87-1.09) and PFS HR 0.92 (95% CI 0.83-1.02)). Significant oxaliplatin irinotecan subgroup interactions were present for PFS with I2 = 82%, p = 0.02. Further analyses of oxaliplatin+EGFR-I trials showed greater efficacy with infusional 5FU regimens (PFS HR 0.82, 95% CI 0.72-0.94) compared to capecitabine (HR 1.09; 95% CI 0.91-1.30) and bolus 5FU (HR 1.07; 95% CI 0.79-1.45); subgroup interaction was present with I2 = 72%, p = 0.03. The oxaliplatin-irinotecan interaction was not evident for infusional 5FU regimens. For AIs, OS benefit was observed with both oxaliplatin-based (HR 0.83) and irinotecan-based (HR 0.77) regimens without significant subgroup interactions. Oxaliplatin+AI trials showed no subgroup interactions by type of FP, whilst an interaction was present for irinotecan+AI trials although aflibercept was only used with infusional FP (I2 = 89.7%, p = 0.002). CONCLUSION AND RELEVANCE: The addition of EGFR-I to irinotecan based chemotherapy has consistent efficacy, regardless of FP regimen, whereas EGFR-I and oxaliplatin-based regimens were most active with infusional 5FU. No such differential activity was observed with the varying chemotherapy schedules when combined with AIs. PMID- 26275293 TI - Phase II Trial of Sorafenib in Patients with Chemotherapy Refractory Metastatic Esophageal and Gastroesophageal (GE) Junction Cancer. AB - PURPOSE: Vascular endothelial growth factor receptor (VEGFR2) directed therapies result in a modest survival benefit for patients with advanced esophageal and gastroesophageal (GE) junction cancer. Platelet-derived growth factor receptor (PDGFR) may contribute to escape from VEGFR2 inhibition. We evaluated the efficacy of sorafenib, a broad spectrum tyrosine kinase inhibitor targeting VEGFR2 and PDGFR as well as RET and RAF1, in patients with metastatic chemotherapy refractory esophageal and GE junction cancer. PATIENTS AND METHODS: This phase II trial of sorafenib 400 mg twice daily enrolled chemotherapy refractory patients with metastatic esophageal and GE junction cancer with primary endpoint of progression-free survival (PFS) rate at two months. Secondary endpoints included overall survival, objective response rate and toxicity. RESULTS: Among 34 patients, 8 week Kaplan-Meier estimated PFS was 61% (90%CI 45 to 73%). Median PFS is 3.6 months (95% CI 1.8 to 3.9 months), with median overall survival OS 9.7 months (95% CI 5.9 to 11.6 months). Grade 3 toxicities were uncommon and included hand foot skin reaction, rash, dehydration and fatigue. One patient (3%) with ongoing complete response and remains on trial for over 5 years. Whole exome sequencing of this tumor revealed mutations in many cancer associated genes including ARID1A, PIK3CA, and TP53, and focal amplifications of HMGA2 and MET. CONCLUSION: Sorafenib therapy results in disease stabilization and encouraging PFS in patients with refractory esophageal and GE junction cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT00917462. PMID- 26275296 TI - Drought Increases Consumer Pressure on Oyster Reefs in Florida, USA. AB - Coastal economies and ecosystems have historically depended on oyster reefs, but this habitat has declined globally by 85% because of anthropogenic activities. In a Florida estuary, we investigated the cause of newly reported losses of oysters. We found that the oyster reefs have deteriorated from north to south and that this deterioration was positively correlated with the abundance of carnivorous conchs and water salinity. In experiments across these gradients, oysters survived regardless of salinity if conchs were excluded. After determining that conchs were the proximal cause of oyster loss, we tested whether elevated water salinity was linked to conch abundance either by increasing conch growth and survivorship or by decreasing the abundance of a predator of conchs. In field experiments across a salinity gradient, we failed to detect spatial variation in predation on conchs or in conch growth and survivorship. A laboratory experiment, however, demonstrated the role of salinity by showing that conch larvae failed to survive at low salinities. Because this estuary's salinity increased in 2006 in response to reduced inputs of freshwater, we concluded that the ultimate cause of oyster decline was an increase in salinity. According to records from 2002 to 2012, oyster harvests have remained steady in the northernmost estuaries of this ecoregion (characterized by high reef biomass, low salinity, and low conch abundance) but have declined in the southernmost estuaries (characterized by lower reef biomass, increases in salinity, and increases in conch abundance). Oyster conservation in this ecoregion, which is probably one of the few that still support viable oyster populations, may be undermined by drought-induced increases in salinity causing an increased abundance of carnivorous conchs. PMID- 26275295 TI - The hMLH1 -93G>A Polymorphism and Risk of Ovarian Cancer in the Chinese Population. AB - BACKGROUND: As a mismatch repair (MMR) gene, hMLH1 plays an important role in the maintenance of chromosomal integrity. Several studies have investigated the associations of hMLH1 -93G>A (rs1800734) and Ile219Val (rs1799977) in diverse tumor types with discordant results, but their roles in ovarian cancer in the Chinese population remains to be elucidated. METHODS: In a case-control analysis, we assessed the association between these two polymorphisms and ovarian cancer risk in 421 ovarian cancer patients and 689 control subjects in the Chinese population using logistic regression. RESULTS: We found that the variant hMLH1 genotypes (-93AA and AG) are associated with risk of ovarian cancer (adjusted odds ratio [OR] = 2.02, 95% confidence interval [CI] = 1.42-2.89) compared with the -93GG genotype. The A allele increases the risk of ovarian cancer in a dose dependent manner (P<10-4). Functional test showed that -93A allele increased hMLH1 promoter transcriptional activity and the luciferase activity. However, no significant difference was found in the genotype frequencies at the Ile219Val site between the cases and controls. CONCLUSIONS: These findings indicate that the -93G>A polymorphism in hMLH1 may affect ovarian cancer susceptibility in the Chinese population. PMID- 26275297 TI - Economic Performance and Sustainability of a Novel Intercropping System on the North China Plain. AB - Double cropping of wheat and maize is common on the North China Plain, but it provides limited income to rural households due to the small farm sizes in the region. Local farmers in Quzhou County have therefore innovated their production system by integration of watermelon as a companion cash crop into the system. We examine the economic performance and sustainability of this novel intercropping system using crop yield data from 2010 to 2012 and farm household survey data collected in 2012. Our results show that the gross margin of the intercropping system exceeded that of the double cropping system by more than 50% in 2012. Labor use in the intercropping system was more than three times that in double cropping. The lower returns per labor hour in intercropping, however, exceeded the average off-farm wage in the region by a significant margin. Nutrient surpluses and irrigation water use are significant larger under the intercropping system. We conclude that the novel wheat-maize/watermelon intercropping system contributes to rural poverty alleviation and household-level food security, by raising farm incomes and generating more employment, but needs further improvement to enhance its sustainability. PMID- 26275299 TI - Correction: The First Paenibacillus larvae Bacteriophage Endolysin (PlyPl23) with High Potential to Control American Foulbrood. PMID- 26275298 TI - Development of Resistance to Pyrethroid in Culex pipiens pallens Population under Different Insecticide Selection Pressures. AB - Current vector control programs are largely dependent on pyrethroids, which are the most commonly used and only insecticides recommended by the World Health Organization for insecticide-treated nets (ITNs). However, the rapid spread of pyrethroid resistance worldwide compromises the effectiveness of control programs and threatens public health. Since few new insecticide classes for vector control are anticipated, limiting the development of resistance is crucial for prolonging efficacy of pyrethroids. In this study, we exposed a field-collected population of Culex pipiens pallens to different insecticide selection intensities to dynamically monitor the development of resistance. Moreover, we detected kdr mutations and three detoxification enzyme activities in order to explore the evolutionary mechanism of pyrethroid resistance. Our results revealed that the level of pyrethroid resistance was proportional to the insecticide selection pressure. The kdr and metabolic resistance both contributed to pyrethroid resistance in the Cx. pipiens pallens populations, but they had different roles under different selection pressures. We have provided important evidence for better understanding of the development and mechanisms of pyrethroid resistance which may guide future insecticide use and vector management in order to avoid or delay resistance. PMID- 26275300 TI - Correction: Impact of Vitamin D Replacement on Markers of Glucose Metabolism and Cardio-Metabolic Risk in Women with Former Gestational Diabetes--A Double-Blind, Randomized Controlled Trial. PMID- 26275301 TI - A Study on the Application of the Information-Motivation-Behavioral Skills (IMB) Model on Rational Drug Use Behavior among Second-Level Hospital Outpatients in Anhui, China. AB - BACKGROUND: The high prevalence of risky irrational drug use behaviors mean that outpatients face high risks of drug resistance and even death. This study represents the first application of the Information-Motivation-Behavioral Skills (IMB) model on rational drug use behavior among second-level hospital outpatients from three prefecture-level cities in Anhui, China. Using the IMB model, our study examined predictors of rational drug use behavior and determined the associations between the model constructs. METHODS: This study was conducted with a sample of 1,214 outpatients aged 18 years and older in Anhui second-level hospitals and applied the structural equation model (SEM) to test predictive relations among the IMB model variables related to rational drug use behavior. RESULTS: Age, information and motivation had significant direct effects on rational drug use behavior. Behavioral skills as an intermediate variable also significantly predicted more rational drug use behavior. Female gender, higher educational level, more information and more motivation predicted more behavioral skills. In addition, there were significant indirect impacts on rational drug use behavior mediated through behavioral skills. CONCLUSIONS: The IMB-based model explained the relationships between the constructs and rational drug use behavior of outpatients in detail, and it suggests that future interventions among second level hospital outpatients should consider demographic characteristics and should focus on improving motivation and behavioral skills in addition to the publicity of knowledge. PMID- 26275303 TI - Evaluation of the 2013 Southeast Asian Haze on Solar Generation Performance. AB - Pollution in Southeast Asia is a major public energy problem and the cause of energy losses. A significant problem with respect to this type of pollution is that it decreases energy yield. In this study, two types of photovoltaic (PV) solar arrays were used to evaluate the effect of air pollution. The performance of two types of solar arrays were analysed in this research, namely, two units of a 1 kWp tracking flat photovoltaic (TFP) and two units of a 1 kWp fixed flat photovoltaic arrays (FFP). Data analysis was conducted on 2,190 samples at 30 min intervals from 01st June 2013, when both arrays were washed, until 30th June 2013. The performance was evaluated by using environmental data (irradiation, temperature, dust thickness, and air pollution index), power output, and energy yield. Multiple regression models were predicted in view of the environmental data and PV array output. Results showed that the fixed flat system was more affected by air pollution than the tracking flat plate. The contribution of this work is that it considers two types of photovoltaic arrays under the Southeast Asian pollution 2013. PMID- 26275302 TI - Measuring Health Utilities in Children and Adolescents: A Systematic Review of the Literature. AB - BACKGROUND: The objective of this review was to evaluate the use of all direct and indirect methods used to estimate health utilities in both children and adolescents. Utilities measured pre- and post-intervention are combined with the time over which health states are experienced to calculate quality-adjusted life years (QALYs). Cost-utility analyses (CUAs) estimate the cost-effectiveness of health technologies based on their costs and benefits using QALYs as a measure of benefit. The accurate measurement of QALYs is dependent on using appropriate methods to elicit health utilities. OBJECTIVE: We sought studies that measured health utilities directly from patients or their proxies. We did not exclude those studies that also included adults in the analysis, but excluded those studies focused only on adults. METHODS AND FINDINGS: We evaluated 90 studies from a total of 1,780 selected from the databases. 47 (52%) studies were CUAs incorporated into randomised clinical trials; 23 (26%) were health-state utility assessments; 8 (9%) validated methods and 12 (13%) compared existing or new methods. 22 unique direct or indirect calculation methods were used a total of 137 times. Direct calculation through standard gamble, time trade-off and visual analogue scale was used 32 times. The EuroQol EQ-5D was the most frequently-used single method, selected for 41 studies. 15 of the methods used were generic methods and the remaining 7 were disease-specific. 48 of the 90 studies (53%) used some form of proxy, with 26 (29%) using proxies exclusively to estimate health utilities. CONCLUSIONS: Several child- and adolescent-specific methods are still being developed and validated, leaving many studies using methods that have not been designed or validated for use in children or adolescents. Several studies failed to justify using proxy respondents rather than administering the methods directly to the patients. Only two studies examined missing responses to the methods administered with respect to the patients' ages. PMID- 26275305 TI - Successful Neuraxial Analgesia After Recent Epidural Blood Patch. AB - Epidural blood patch is a frequently successful treatment for postdural puncture headache. It is not clear whether a recent epidural blood patch affects subsequent neuraxial analgesia. We describe the case of a patient who received an epidural blood patch for postdural puncture headache and returned 3 days later in active labor, requesting epidural analgesia. The patient successfully received analgesia from a combined spinal epidural without further complications. We discuss the anesthetic considerations for providing neuraxial analgesia after a recent epidural blood patch. PMID- 26275304 TI - Analysis of Tospovirus NSs Proteins in Suppression of Systemic Silencing. AB - RNA silencing is a sequence-specific gene regulation mechanism that in plants also acts antiviral. In order to counteract antiviral RNA silencing, viruses have evolved RNA silencing suppressors (RSS). In the case of tospoviruses, the non structural NSs protein has been identified as the RSS. Although the tomato spotted wilt virus (TSWV) tospovirus NSs protein has been shown to exhibit affinity to long and small dsRNA molecules, its ability to suppress the non-cell autonomous part of RNA silencing has only been studied to a limited extent. Here, the NSs proteins of TSWV, groundnut ringspot virus (GRSV) and tomato yellow ring virus (TYRV), representatives for three distinct tospovirus species, have been studied on their ability and strength to suppress local and systemic silencing. A system has been developed to quantify suppression of GFP silencing in Nicotiana benthamiana 16C lines, to allow a comparison of relative RNA silencing suppressor strength. It is shown that NSs of all three tospoviruses are suppressors of local and systemic silencing. Unexpectedly, suppression of systemic RNA silencing by NSsTYRV was just as strong as those by NSsTSWV and NSsGRSV, even though NSsTYRV was expressed in lower amounts. Using the system established, a set of selected NSsTSWV gene constructs mutated in predicted RNA binding domains, as well as NSs from TSWV isolates 160 and 171 (resistance breakers of the Tsw resistance gene), were analyzed for their ability to suppress systemic GFP silencing. The results indicate another mode of RNA silencing suppression by NSs that acts further downstream the biogenesis of siRNAs and their sequestration. The findings are discussed in light of the affinity of NSs for small and long dsRNA, and recent mutant screen of NSsTSWV to map domains required for RSS activity and triggering of Tsw-governed resistance. PMID- 26275306 TI - Atypical Presentation of a Pulmonary Embolism in the Perioperative Setting. AB - We present the case of an asymptomatic 82-year-old patient with no coronary artery disease and a negative cardiac workup who presented to the hospital for an elective total knee replacement. The patient had stable vital signs in the preanesthesia holding unit, yet the anesthesiologist recognized new-onset atrial fibrillation on the patient's monitor. The dysrhythmia was confirmed with a 12 lead electrocardiogram. The procedure was canceled, and the patient was sent for additional evaluation. An echocardiogram revealed a pulmonary embolism. This case report illustrates the need for a questioning attitude and diligent monitoring in all phases of perioperative care. PMID- 26275307 TI - Bilateral Blindness due to Ischemic Optic Nerve Neuropathy After Abdominal Surgery. AB - Postoperative blindness is an unpredictable, devastating, and yet not-uncommon complication of anesthesia. We present the case of a patient who suffered bilateral loss of eyesight after surgery. The diagnostic evidence led us to believe that it was bilateral posterior ischemic optic neuropathy; however, the true mechanisms of damage remain a matter of speculation. PMID- 26275308 TI - Dependent Lung Tension Pneumothorax During 1-Lung Ventilation: Treatment by Transmediastinal Thoracentesis. AB - Contralateral tension pneumothorax during 1-lung ventilation is rare but life threatening. We report the case of a patient who developed tension pneumothorax of the dependent lung during 1-lung ventilation while the surgeon was anastomosing the bronchi after sleeve lobectomy. Ventilation was not possible in either the dependent or nondependent lung, leading to severe desaturation and cardiac arrest. While the surgeons were administering direct cardiac compression, we suspected tension pneumothorax. As soon as the surgeons pierced the mediastinal pleura, adequate circulation was restored. Immediate diagnosis and treatment is important for this complication. PMID- 26275309 TI - Anesthetic Management for Resection of Bilateral Pulmonary Artery Sarcoma. AB - We describe a patient who presented with a bilateral pulmonary artery sarcoma, initially treated as pulmonary embolism, that necessitated concomitant pulmonary endarterectomy and pneumonectomy. We reviewed the anesthetic management used for this procedure, which bears many similarities to the management of patients undergoing pulmonary thromboendarterectomy. Right ventricular failure, pulmonary hemorrhage, and cerebral ischemia due to circulatory arrest are life-threatening perioperative complications. The anesthesiologist can play a key role in the prevention (or timely recognition and treatment) of these perioperative complications by establishing adequate hemodynamic, echocardiographic, and neurologic monitoring and by optimizing cardiopulmonary function and coagulation. PMID- 26275312 TI - Correction: Status Epilepticus Induced Spontaneous Dentate Gyrus Spikes: In Vivo Current Source Density Analysis. PMID- 26275310 TI - Reporter Gene Silencing in Targeted Mouse Mutants Is Associated with Promoter CpG Island Methylation. AB - Targeted mutations in mouse disrupt local chromatin structure and may lead to unanticipated local effects. We evaluated targeted gene promoter silencing in a group of six mutants carrying the tm1a Knockout Mouse Project allele containing both a LacZ reporter gene driven by the native promoter and a neo selection cassette. Messenger RNA levels of the reporter gene and targeted gene were assessed by qRT-PCR, and methylation of the promoter CpG islands and LacZ coding sequence were evaluated by sequencing of bisulfite-treated DNA. Mutants were stratified by LacZ staining into presumed Silenced and Expressed reporter genes. Silenced mutants had reduced relative quantities LacZ mRNA and greater CpG Island methylation compared with the Expressed mutant group. Within the silenced group, LacZ coding sequence methylation was significantly and positively correlated with CpG Island methylation, while promoter CpG methylation was only weakly correlated with LacZ gene mRNA. The results support the conclusion that there is promoter silencing in a subset of mutants carrying the tm1a allele. The features of targeted genes which promote local silencing when targeted remain unknown. PMID- 26275311 TI - Diurnal Expression Pattern, Allelic Variation, and Association Analysis Reveal Functional Features of the E1 Gene in Control of Photoperiodic Flowering in Soybean. AB - Although four maturity genes, E1 to E4, in soybean have been successfully cloned, their functional mechanisms and the regulatory network of photoperiodic flowering remain to be elucidated. In this study, we investigated how the diurnal expression pattern of the E1 gene is related to photoperiodic length; and to what extent allelic variation in the B3-like domain of the E1 gene is associated with flowering time phenotype. The bimodal expression of the E1 gene peaked first at around 2 hours after dawn in long-day condition. The basal expression level of E1 was enhanced by the long light phase, and decreased by duration of dark. We identified a 5bp (3 SNP and 2-bp deletion) mutation, referred to an e1-b3a, which occurs in the middle of B3 domain of the E1 gene in the early flowering cultivar Yanhuang 3. Subcellular localization analysis showed that the putative truncated e1-b3a protein was predominately distributed in nuclei, indicating the distribution pattern of e1-b3a was similar to that of E1, but not to that of e1 as. Furthermore, genetic analysis demonstrated allelic variations at the E1 locus significantly underlay flowering time in three F2 populations. Taken together, we can conclude the legume specific E1 gene confers some special features in photoperiodic control of flowering in soybean. Further characterization of the E1 gene will extend our understanding of the soybean flowering pathway in soybean. PMID- 26275313 TI - Epidermotropic B-Cell Lymphoma: A Unique Subset of CXCR3-Positive Marginal Zone Lymphoma. AB - BACKGROUND: Epidermotropic B-cell lymphoma is a very rare entity that has primarily been reported in the literature as anecdotal case reports. The majority of the reported cases exhibit a diffuse skin rash affecting middle-aged to older adults with a male predominance. The exact mechanism of marginal zone B-cell localization to the epidermis is unclear. MATERIAL AND METHODS: To describe a very rare subset of cutaneous B-cell lymphoma and explore potential pathogenetic mechanisms for the epidermotropic tendency, the hospital database and literature review was conducted to isolate cases of epidermotropic B-cell lymphoma. Routine hematoxylin and eosin stain followed by selective phenotypic studies. RESULTS: Two of the cases were encountered in the hospital database, whereas 5 cases have been previously reported; material was requested on previously reported cases and was received on 3 of them. In one of the 2 cases encountered in our database, the patient presented with a progressive skin rash over 7 months resembling pityriasis rosea. Subsequent to a diagnosis of B-cell lymphoma, further staging revealed bone marrow involvement. The other patient, an elderly female, presented with isolated nodules. The biopsies of both cases showed areas of superficial band-like lymphocytic infiltration with large monocytoid appearance and an epidermotropic pattern of lymphocyte migration into the epidermis. Neoplastic cells were extensively positive for CD20, CD79a, and BCL-2 and negative for CD10 and BCL-6. Of interest, a similar pityriasis rosea-like presentation was encountered in the cases reported in the literature. All patients were elderly males with established bone marrow, peripheral blood, and spleen involvement several months to years after the initial cutaneous presentation in 3 of them. None of the patients to date have died of lymphoma. CXCR3 epidermotropic B cells were detected in both our cases and in 3 of the 3 previously published cases. CONCLUSIONS: Epidermotropic B-cell lymphoma represents a subset of marginal zone lymphoma characterized by a papulosquamous rash most frequently resembling pityriasis rosea, occurring almost exclusively in older males. We speculate that aberrant expression of CXCR3 in marginal zone lymphoma of the skin is associated with migration of lymphoma cells to the epidermis and could lead to an epidermotropic pattern given the known role of CXCR3 expression in neoplastic T cells in the localization of mycosis fungoides to the epidermis. There is a tendency toward bone marrow, spleen, and peripheral blood involvement. PMID- 26275314 TI - Matrical Carcinoma With Melanocytic Proliferation and Prominent Squamoid Whorls. AB - Matrical carcinoma (pilomatrix carcinoma) is a rare follicular low-grade malignancy with matrical differentiation. A pigmented variant with admixed dendritic melanocytes is exceedingly rare with only 7 cases reported in the literature. The diagnosis of malignancy can be difficult to establish. The authors report a case of a 79-year-old woman with a matrical carcinoma who presented with an ulcerated nodule on the posterior right leg, measuring 2.2 cm in greatest dimension. The excisional biopsy showed irregularly shaped dermal and subcutaneous nodules ranging in size from 0.1 to 0.5 cm. The nodules were composed of aggregates of large atypical basaloid cells, with multiple, sometimes atypical, mitoses, admixed with ghost cells, and central necrosis en masse. In addition, the neoplasm was characterized by focal marked melanocytic proliferation and multiple whorls of pink eosinophilic material reminiscent of keratin pearls (squamoid whorls). The basaloid cells were positive for beta catenin both in the nuclei and the cytoplasm and negative for BerEp4. S100, Melan A, and HMB45 highlighted the melanocytic dendritic cells. Pan-cytokeratin was negative in the ghost cells and focally positive in the squamoid whorls. Squamoid whorls seem to be a significant feature of matrical carcinoma. PMID- 26275315 TI - Mothers' Perceptions of Labor Support. AB - PURPOSE: The purpose of this study was to describe mothers' perceptions of labor support during childbirth. STUDY DESIGN AND METHODS: A cross-sectional, descriptive, correlational survey design was used. Data were collected using the Bryanton Adaptation of Nursing Support in Labor Questionnaire (BANSILQ) completed by new mothers (n = 260) in the postnatal ward in a Finnish university hospital. Nonparametric methods were used for data analysis. RESULTS: Mothers perceived emotional assistance to be most important. From the list of midwives' labor support behaviors provided in the survey, the following were considered most helpful: giving praise, treating on an individual basis, and answering questions truthfully and understandably. CLINICAL IMPLICATIONS: Emotional, tangible, and informational labor support enhanced the mothers' birth experiences. Labor support should be provided when caring for every mother during childbirth. An evidence-based model of labor support should be used for nursing and midwifery education and clinical practice. PMID- 26275316 TI - Tribute to Margaret Comerford Freda. PMID- 26275317 TI - Editorial overview: Special section: Immunological engineering. PMID- 26275318 TI - Editorial overview: Vaccines: Vaccines for cancer and infectious diseases. PMID- 26275319 TI - Vitamin A deficiency: slow progress towards elimination. PMID- 26275320 TI - Home use of urine pregnancy tests for medical abortion follow-up. PMID- 26275321 TI - Nigeria's new government and public financing for universal health coverage. PMID- 26275322 TI - Ethics in global health research: the need for balance. PMID- 26275323 TI - Breastfeeding and adult intelligence. PMID- 26275324 TI - Breastfeeding and adult intelligence. PMID- 26275325 TI - Breastfeeding and adult intelligence. PMID- 26275326 TI - Breastfeeding and adult intelligence - Authors' reply. PMID- 26275327 TI - Banning of fetal sex determination and changes in sex ratio in India. PMID- 26275328 TI - Strengthening US-Iranian relations through public health. PMID- 26275329 TI - Trends and mortality effects of vitamin A deficiency in children in 138 low income and middle-income countries between 1991 and 2013: a pooled analysis of population-based surveys. AB - BACKGROUND: Vitamin A deficiency is a risk factor for blindness and for mortality from measles and diarrhoea in children aged 6-59 months. We aimed to estimate trends in the prevalence of vitamin A deficiency between 1991 and 2013 and its mortality burden in low-income and middle-income countries. METHODS: We collated 134 population-representative data sources from 83 countries with measured serum retinol concentration data. We used a Bayesian hierarchical model to estimate the prevalence of vitamin A deficiency, defined as a serum retinol concentration lower than 0.70 MUmol/L. We estimated the relative risks (RRs) for the effects of vitamin A deficiency on mortality from measles and diarrhoea by pooling effect sizes from randomised trials of vitamin A supplementation. We used information about prevalences of deficiency, RRs, and number of cause-specific child deaths to estimate deaths attributable to vitamin A deficiency. All analyses included a systematic quantification of uncertainty. FINDINGS: In 1991, 39% (95% credible interval 27-52) of children aged 6-59 months in low-income and middle-income countries were vitamin A deficient. In 2013, the prevalence of deficiency was 29% (17-42; posterior probability [PP] of being a true decline=0.81). Vitamin A deficiency significantly declined in east and southeast Asia and Oceania from 42% (19-70) to 6% (1-16; PP>0.99); a decline in Latin America and the Caribbean from 21% (11-33) to 11% (4-23; PP=0.89) also occurred. In 2013, the prevalence of deficiency was highest in sub-Saharan Africa (48%; 25-75) and south Asia (44%; 13 79). 94 500 (54 200-146 800) deaths from diarrhoea and 11 200 (4300-20 500) deaths from measles were attributable to vitamin A deficiency in 2013, which accounted for 1.7% (1.0-2.6) of all deaths in children younger than 5 years in low-income and middle-income countries. More than 95% of these deaths occurred in sub-Saharan Africa and south Asia. INTERPRETATION: Vitamin A deficiency remains prevalent in south Asia and sub-Saharan Africa. Deaths attributable to this deficiency have decreased over time worldwide, and have been almost eliminated in regions other than south Asia and sub-Saharan Africa. This new evidence for both prevalence and absolute burden of vitamin A deficiency should be used to reconsider, and possibly revise, the list of priority countries for high-dose vitamin A supplementation such that a country's priority status takes into account both the prevalence of deficiency and the expected mortality benefits of supplementation. FUNDIN: Bill & Melinda Gates Foundation, Grand Challenges Canada, UK Medical Research Council. PMID- 26275330 TI - Self-assessment of the outcome of early medical abortion versus clinic follow-up in India: a randomised, controlled, non-inferiority trial. AB - BACKGROUND: The need for multiple clinical visits remains a barrier to women accessing safe legal medical abortion services. Alternatives to routine clinic follow-up visits have not been assessed in rural low-resource settings. We compared the effectiveness of standard clinic follow-up versus home assessment of outcome of medical abortion in a low-resource setting. METHODS: This randomised, controlled, non-inferiority trial was done in six health centres (three rural, three urban) in Rajasthan, India. Women seeking early medical abortion up to 9 weeks of gestation were randomly assigned (1:1) to either routine clinic follow up or self-assessment at home. Randomisation was done with a computer-generated randomisation sequence, with a block size of six. The study was not blinded. Women in the home-assessment group were advised to use a pictorial instruction sheet and take a low-sensitivity urine pregnancy test at home, 10-14 days after intake of mifepristone, and were contacted by a home visit or telephone call to record the outcome of the abortion. The primary (non-inferiority) outcome was complete abortion without continuing pregnancy or need for surgical evacuation or additional mifepristone and misoprostol. The non-inferiority margin for the risk difference was 5%. All participants with a reported primary outcome and who followed the clinical protocol were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT01827995. FINDINGS: Between April 23, 2013, and May 15, 2014, 731 women were recruited and assigned to clinic follow-up (n=366) or home assessment (n=365), of whom 700 were analysed for the main outcomes (n=336 and n=364, respectively). Complete abortion without continuing pregnancy, surgical intervention, or additional mifepristone and misoprostol was reported in 313 (93%) of 336 women in the clinic follow-up group and 347 (95%) of 364 women in the home-assessment group (difference -2.2%, 95% CI -5.9 to 1.6). One case of haemorrhage occurred in each group (rate of adverse events 0.3% in each group); no other adverse events were noted. INTERPRETATION: Home assessment of medical abortion outcome with a low-sensitivity urine pregnancy test is non-inferior to clinic follow-up, and could be introduced instead of a clinic follow-up visit in a low-resource setting. PMID- 26275331 TI - Comparison of endoscopic endonasal and bifrontal craniotomy approaches for olfactory groove meningiomas: A matched pair analysis of outcomes and frontal lobe changes on MRI. AB - We compare the outcomes and postoperative MRI changes of endoscopic endonasal (EEA) and bifrontal craniotomy (BFC) approaches for olfactory groove meningiomas (OGM). All patients who underwent either BFC or EEA for OGM were eligible. Matched pairs were created by matching tumor volumes of an EEA patient with a BFC patient, and matching the timing of the postoperative scans. The tumor dimensions, peritumoral edema, resectability issues, and frontal lobe changes were recorded based on preoperative and postoperative MRI. Postoperative fluid attenuated inversion recovery (FLAIR) hyperintensity and residual cystic cavity (porencephalic cave) volume were compared using univariable and multivariable analyses. From a total of 70 patients (46 EEA, 24 BFC), 10 matched pairs (20 patients) were created. Three patients (30%) in the EEA group and two (20%) in the BFC had postoperative cerebrospinal fluid leaks (p=0.61). Gross total resections were achieved in seven (70%) of the EEA group and nine (90%) of the BFC group (p=0.26), and one patient from each group developed a recurrence. On postoperative MRI, there was no significant difference in FLAIR signal volumes between EEA and BFC approaches (6.9 versus 13.3 cm(3); p=0.17) or in porencephalic cave volumes (1.7 versus 5.0 cm(3); p=0.11) in univariable analysis. However, in a multivariable analysis, EEA was associated with less postoperative FLAIR change (p=0.02) after adjusting for the volume of preoperative edema. This study provides preliminary evidence that EEA is associated with quantifiable improvements in postoperative frontal lobe imaging. PMID- 26275332 TI - Copy number variants associated with epilepsy from gene expression microarrays. AB - We aimed to identify novel copy number variations (CNV) that might contribute to the pathogenesis of epilepsy. Epilepsy is a common brain disorder characterized by recurring seizures and various serious comorbidities, including respiratory, cardiovascular, and neurologic dysfunction. CNV have recently been considered as important risk factors for epilepsy. With public gene expression data from brain tissue of 23 epilepsy patients and 23 healthy controls, we detected CNV using the R language package CAFE. Real-time quantitative polymerase chain reaction validation was performed in a further nine patients and 10 controls. Functional analyses of the genes in the validated CNV were also carried out, using Ingenuity pathway analysis. Three copy number abnormalities (19q13.33, 19q13.11 and 4q35.1) were detected with the gene expression data. The duplication in 19q13.33 (approximately 1.22 million bases) was further validated in three additional epilepsy patients, and the deletion in 19q13.11 (approximately 855 kilobases) was further validated in another two epilepsy patients. The functional analyses of the genes in these two CNV suggested that they may be involved in the pathogenesis of epilepsy. The CNV that we detected may be common genetic etiological factors of epilepsy, and there is potential for the identification of a novel biomarker for treatment from these CNV regions. PMID- 26275333 TI - Variety in snack servings as determinant for acceptance in school children. AB - Variety within a meal is known to increase intake. However, intake of certain food items (e.g. vegetables) in children is consistently below recommendations, and increasing the consumption of such food would lead to health benefits. This study investigated how different levels of food variety influence children's acceptance. A total of 132 children, aged from 9 to 11 years, were exposed to vegetables, fruits and nut snacks during mid-morning break at school. Two different sets of stimuli were used in a within subject design: Classical Variety (CV), i.e. serving of different foods and Perceived Variety (PV), i.e. serving of the same food in different shapes. For each set, three levels of variety in the servings were tested: low, medium, and high. Intake and liking were determined for each serving set. ANOVA results showed that intake of CV set decreased according to the level of variety, whereas results of PV set only showed an increase of liking with increasing levels of variety. Adding more variations of products appeared to be less successful on consumption despite changing the liking of the products, may be because consumption is more affected by acceptability and familiarity for the stimuli than by variety. PMID- 26275336 TI - Festschrift to highlight the career of Abba J. Kastin as a founding editor, researcher, and educator in the peptide field. Preface. PMID- 26275335 TI - The membrane-active amphibian peptide caerin 1.8 inhibits fibril formation of amyloid beta1-42. AB - The amphibian host-defense peptide caerin 1.8 [(1)GLFKVLGSV(10)AKHLLPHVVP(20)VIAEKL(NH2)] inhibits fibril formation of amyloid beta 1-42 [(1)DAEFRHDSG(10)YEVHHQKLVF(20)FAEDVGSNKG(30)AIIGLMVGGV(40)VIA] [Abeta42] (the major precursor of the extracellular fibrillar deposits of Alzheimer's disease). Some truncated forms of caerin 1.8 also inhibit fibril formation of Abeta42. For example, caerin 1.8 (1-13) [(1)GLFKVLGSV(10)AKHL(NH2) and caerin 1.8 (22-25) [KVLGSV(10)AKHLLPHVVP(20)VIAEKL(NH2)] show 85% and 75% respectively of the inhibition activity of the parent caerin 1.8. The synthetic peptide KLVFFKKKKKK is a known inhibitor of Abeta42 fibril formation, and was used as a standard in this study. Caerin 1.8 is the more effective fibril inhibitor. IC50 values (+/- 15%) are caerin 1.8 (75 MUM) and KLVFFKKKKKK (370 MUM). MALDI mass spectrometry shows the presence of a small peak corresponding to a protonated 1:1 adduct [caerin 1.8/Abeta42]H(+). Molecular dynamics simulation suggests that both hydrogen bonding and hydrophobic interactions between Abeta42 and caerin 1.8 facilitate the formation of a 1:1 complex in water. Fibril formation from Abeta42 has been proposed to be based around the (16)KLVF(20)F region of Abeta42; this region in the 1:1 complex is partially blocked from attachment of a further molecule of Abeta42. PMID- 26275334 TI - Greater anterior cingulate activation and connectivity in response to visual and auditory high-calorie food cues in binge eating: Preliminary findings. AB - Obese individuals show altered neural responses to high-calorie food cues. Individuals with binge eating [BE], who exhibit heightened impulsivity and emotionality, may show a related but distinct pattern of irregular neural responses. However, few neuroimaging studies have compared BE and non-BE groups. To examine neural responses to food cues in BE, 10 women with BE and 10 women without BE (non-BE) who were matched for obesity (5 obese and 5 lean in each group) underwent fMRI scanning during presentation of visual (picture) and auditory (spoken word) cues representing high energy density (ED) foods, low-ED foods, and non-foods. We then compared regional brain activation in BE vs. non-BE groups for high-ED vs. low-ED foods. To explore differences in functional connectivity, we also compared psychophysiologic interactions [PPI] with dorsal anterior cingulate cortex [dACC] for BE vs. non-BE groups. Region of interest (ROI) analyses revealed that the BE group showed more activation than the non-BE group in the dACC, with no activation differences in the striatum or orbitofrontal cortex [OFC]. Exploratory PPI analyses revealed a trend towards greater functional connectivity with dACC in the insula, cerebellum, and supramarginal gyrus in the BE vs. non-BE group. Our results suggest that women with BE show hyper-responsivity in the dACC as well as increased coupling with other brain regions when presented with high-ED cues. These differences are independent of body weight, and appear to be associated with the BE phenotype. PMID- 26275337 TI - Regulation of gut hormone secretion. Studies using isolated perfused intestines. AB - The incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from enteroendocrine cells in the intestine along with other gut hormones (PYY, CCK and neurotensin) shown to affect metabolism and/or appetite. The secretion of many gut hormones is highly increased after gastric bypass operations, which have turned out to be an effective therapy of not only obesity but also type 2 diabetes. These effects are likely to be due, at least in part, to increases in the secretion of these gut hormones (except GIP). Therefore, stimulation of the endogenous hormone represents an appealing therapeutic strategy, which has spurred an interest in understanding the regulation of gut hormone secretion and a search for particularly GLP-1 and PYY secretagogues. The secretion of the gut hormones is stimulated by oral intake of nutrients often including carbohydrate, protein and lipid. This review focuses on stimulators of gut hormone secretion, the mechanisms involved, and in particular models used to investigate secretion. A major break-through in this field was the development of methods to identify and isolate specific hormone producing cells, which allow detailed mapping of the expression profiles of these cells, whereas they are less suitable for physiological studies of secretion. Isolated perfused preparations of mouse and rat intestines have proven to be reliable models for dynamic hormone secretion and should be able to bridge the gap between the molecular details derived from the single cells to the integrated patterns observed in the intact animals. PMID- 26275338 TI - Idiopathic giant cell myocarditis in childhood: A case report. AB - Idiopathic giant cell myocarditis is a rare entity of unknown origin, which causes sudden death in more than half of the affected patients. It is rarely seen in childhood, and might result in death due to heart failure and ventricular arrhythmias. Idiopathic giant cell myocarditis is mostly diagnosed at autopsy incidentally. Here we present a rare case of childhood idiopathic giant cell myocarditis. A 10-year old boy found dead in his bed in the morning. Interview with family members revealed death the boy was in good health conditions apart from being overweight. At autopsy, external examination was completely normal. Internal examination revealed normal findings; the heart was 297g and macroscopically normal. No traces of any toxic agents detected in complete toxicological analyses. Areas characterized with granulomatous lesions, lymphocytes, histiocytes, and multinucleated giant cells were observed in myocardium at histopathological examination. No necrosis was observed in granulomatous areas. Tuberculosis was negative in the PCR assays. There were no signs indicative of fungal infection, and clinical status of the case was not compatible with the sarcoidosis. In this respect death was attributed to idiopathic giant cell myocarditis. PMID- 26275340 TI - Physiological, psychological and functional changes with whole body vibration exercise in the elderly: FEVER methodology and protocols. AB - BACKGROUND: The FEVER (Frail Elderly Vibration Exercise Response) study aims to address a paucity of research focusing on the use of Whole Body Vibration (WBV) by frail elderly who, with the highest levels of dependence and fall-related hospitalisation/mortality, potentially stand to benefit most from such accessible exercise. METHODS: FEVER is an open, randomised feasibility study, consisting of multiple parallel arms and a longitudinal element. Rest-home residents aged 70+years will be recruited, and assigned to a WBV-exercise group (WBV), a simulated-WBV-exercise group (SIM), or a control group (CON). WBV- and SIM participants will undergo thrice-weekly sessions (<20-min each, including 1:1 ratio of exercise:rest) for a 16-week exercise intervention period, whilst CON participants will receive no intervention beyond normal care. WBV-exercise will start with 5?1-minute sessions (6Hz, 2mm amplitude), progressing to 10?1-minute sessions at which time Hz/amplitude can be increased if desired. During WBV exercise, participants will maintain an isometric knee flexion of ~20 degrees (+/-5 degrees ), to dampen WBV further up the body. RESULTS: Outcomes will include assessments of functionality (primary outcome), Quality of Life, bone health and cardiovascular function. Measures will be conducted at baseline, 8 weeks and 16-weeks of the intervention, and 3-, 6- and 12-months post intervention. As a protocol paper, there are no specific results to present; our current purpose is to share the study design with the scientific community. CONCLUSIONS: The FEVER study aims to investigate the beneficial effects of WBV exercise in the frail elderly, ascertain an effective training regime and for the first-time identify a time-line of detraining. PMID- 26275339 TI - Phase I clinical evaluation of seasonal influenza hemagglutinin (HA) DNA vaccine prime followed by trivalent influenza inactivated vaccine (IIV3) boost. AB - : Annual influenza vaccination reduces the risks of influenza when the vaccines are well matched to circulating strains, but development of an approach that induces broader and more durable immune responses would be beneficial. We conducted two companion Phase 1 studies, VRC 307 and VRC 309, over sequential seasons (2008-2009 and 2009-2010) in which only the influenza B strain component of the vaccines differed. Objectives were safety and immunogenicity of prime boost vaccination schedules. A schedule of DNA vaccine encoding for seasonal influenza hemagglutinins (HA) prime followed by seasonal trivalent influenza inactivated vaccine (IIV3) boost (HA DNA-IIV3) was compared to placebo (PBS)-IIV3 or IIV3-IIV3. Cumulatively, 111 adults were randomized to HA DNA-IIV3 (n=66), PBS IIV3 (n=25) or IIV3-IIV3 (n=20). Safety was assessed by clinical observations, laboratory parameters and 7-day solicited reactogenicity. The seasonal HA DNA prime-IIV3 boost regimen was evaluated as safe and well tolerated. There were no serious adverse events. The local and systemic reactogenicity for HA DNA, IIV and placebo were reported predominantly as none or mild within the first 5days post vaccination. There was no significant difference in immunogenicity detected between the treatment groups as evaluated by hemagglutination inhibition (HAI) assay. The studies demonstrated the safety and immunogenicity of seasonal HA DNA IIV3 regimen, but the 3-4week prime-boost interval was suboptimal for improving influenza-specific immune responses. This is consistent with observations in avian H5 DNA vaccine prime-boost studies in which a long interval, but not a short interval, was associated with improved immunogenicity. TRIAL REGISTRATION: NCT00858611 for VRC 307 and NCT00995982 for VRC 309. PMID- 26275341 TI - The two interfaces of the STAT1 N-terminus exhibit opposite functions in IFNgamma regulated gene expression. AB - Defective cooperative DNA binding of STAT1 (signal transducer and activator of transcription 1) transcription factor has impact on interferon-gamma(IFNgamma) regulated transcriptional responses. In this study, we generated N-terminal gain of-function mutants of this protein which exhibited hyperactive cooperativity and assessed their functional consequences on gene expression. Our data show that four negatively charged, surface-exposed amino acid residues in the N-terminal domain dimer are engaged in the disassembly of tyrosine-phosphorylated tetrameric complexes on DNA and prevent the occurrence of higher-order STAT1 oligomers on low-affinity DNA binding sites. Owing to their improved tetramer stability, the N terminal mutants showed relaxed sequence requirements for the binding to DNA as compared to the wild-type protein. Similarly to a STAT1 mutant with impaired tetramerization, the N-terminal gain-of-function mutants showed elevated tyrosine phosphorylation levels and prolonged nuclear accumulation upon stimulation of cells with IFNgamma. However, in contrast to the global impairment of IFNgamma signalling in tetramerization-deficient mutants, the transcriptional consequences of the N-terminal gain-of-function mutants are rather distinct and affect gene expression locally in a promoter-specific manner. Thus, we conclude that the STAT1 N-domain acts as a double-edged sword: while one interface is crucial for the formation of tetrameric complexes on IFNgamma-regulated promoters, the opposite interface harbours an inhibitory mechanism that limits the accumulation of higher-order oligomers simply by disrupting cooperative DNA binding. PMID- 26275342 TI - CD100 and plexins B2 and B1 mediate monocyte-endothelial cell adhesion and might take part in atherogenesis. AB - Leukocyte migration is essential for the function of the immune system. Their recruitment from the vessels to the tissues involves sequential molecular interactions between leukocytes and endothelial cells (ECs). Many adhesion molecules involved in this process have already been described. However, additional molecules may be important in this interaction, and here we explore the potential role for CD100 and plexins in monocyte-EC binding. CD100 was shown to be involved in platelet-endothelial cell interaction, an important step in atherogenesis and thrombus formation. In a recent work we have described CD100 expression in monocytes and in macrophages and foam cells of human atherosclerotic plaques. In the present work, we have identified plexin B2 as a putative CD100 receptor in these cells. We have detected CD100 expression in the endothelium as well as in in vitro cultured endothelial cells. Blocking of CD100, plexin B1 and/or B2 in adhesion experiments have shown that both CD100 and plexins act as adhesion molecules involved in monocyte-endothelial cell binding. This effect may be mediated by CD100 expressed in both cell types, probably coupled to the receptors endothelial plexin B1 and monocytic plexin B2. These results can bring new insights about a possible biological activity of CD100 in monocyte adhesion and atherosclerosis, as well as a future candidate for targeting therapeutics. PMID- 26275343 TI - Skin donors and human skin allografts: evaluation of an 11-year practice and discard in a referral tissue bank. AB - The Saint Louis hospital tissue bank provides skin allografts to pediatric and adult burn units in the Paris area. The aim of this study was to analyze our activity during the last 11 years focusing on the reasons for skin discard. Skin is procured solely from the back of the body, which is divided into 10 zones that are harvested and processed separately. This retrospective study included all skin donors harvested between June 2002 and June 2013, representing a total of 336 donors and 2770 zones. The donors were multiorgan heart-beating donors in 91 % of cases (n = 307). The main reason for discarding harvested skin was microbial contamination, detected in 99 donors (29 %). Most contaminants were of low pathogenicity. Other reasons for discard included positive serologic tests for 2 donors [17 zones (0.61 %)], unsuitable physical skin characteristics for 3 zones (0.11 %), the donor's medical history for 53 zones (1.91 %), and technical issues with processing or distribution for 61 zones (2.2 %). In our experience, microbial contamination continues to be the main reason for discarding potential skin allografts. However, discards are limited by separate harvesting and processing of multiple zones in each donor. PMID- 26275344 TI - Bill Whelan's impact on my life and career. AB - In this tribute to Bill Whelan on his 90th birthday, I recount the huge impact that Bill has had on my life and career, and briefly recall the contributions that my laboratory made to the understanding of glycogenin in the late 1980s. In particular, the demonstration that glycogenin and glycogen synthase form a complex, and that glycogenin is a glucosyl transferase that autoglucosylates itself at tyrosine 194. PMID- 26275345 TI - Don't stop till you get enough: Factors driving men towards muscularity. AB - This study tested a modified Tripartite Influence Model with 307 men (age M=27.05; SD=6.25). Sociocultural influences (media and male peers) were predicted to be associated with both internalisation of the muscular ideal and body comparisons, which in turn were predicted to be associated with muscle dissatisfaction and then drive for muscularity behaviours. The model was only partially supported. The results suggested that, contrary to what was predicted, muscle dissatisfaction was not related to drive for muscularity behaviours. Instead, internalisation of the muscular ideal was found to lead to body comparisons, which in turn were found to lead to drive for muscularity behaviours. In addition, internalisation and male peer influence were found to lead to muscle dissatisfaction; male peer influence and internalisation were found to lead to body comparisons; and both media and male peer influences were found to lead to internalisation. PMID- 26275346 TI - Measuring Brain Stimulation Induced Changes in Cortical Properties Using TMS-EEG. AB - Neuromodulatory brain stimulation can induce plastic reorganization of cortical circuits that persist beyond the period of stimulation. Most of our current knowledge about the physiological properties has been derived from the motor cortex. The integration of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) is a valuable method for directly probing excitability, connectivity and oscillatory dynamics of regions throughout the brain. Offering in depth measurement of cortical reactivity, TMS-EEG allows the evaluation of TMS-evoked components that may act as a marker for cortical excitation and inhibition. A growing body of research is using concurrent TMS and EEG (TMS-EEG) to explore the effects of different neuromodulatory techniques such as repetitive TMS and transcranial direct current stimulation on cortical function, particularly in non-motor regions. In this review, we outline studies examining TMS-evoked potentials and oscillations before and after, or during a single session of brain stimulation. Investigating these studies will aid in our understanding of mechanisms involved in the modulation of excitability and inhibition by neuroplasticity following different stimulation paradigms. PMID- 26275347 TI - Peripheral leukocyte expression of the potential biomarker proteins Bdnf, Sirt1, and Psen1 is not regulated by promoter methylation in Alzheimer's disease patients. AB - The identification of Alzheimer's disease (AD) biomarkers is crucial to support drug discovery. Within putative biomarkers, peripheral Bdnf levels correlate with cognitive decline and AD, although conflicting findings are reported. Sirtuin 1 (Sirt1) serum levels are lower in AD patients and Presenilin 1 (Psen1) is expressed by blood cells. DNA methylation is altered in AD patients, suggesting that epigenetic mechanisms play a role in AD pathophysiology. The objective of this study was to investigate promoter methylation levels of potential biomarkers in AD cases and controls. Peripheral blood DNA methylation levels were analysed by methylation-specific primer real-time PCR. Bdnf promoter methylation levels did not differ between AD patients and controls. Similarly, Sirt1 promoter revealed minimal levels of methylation which did not display significant differences between groups. No significant difference was revealed between AD patients and controls also in Psen1 methylation, showing a large variability of values among subjects. Although peripheral Bdnf expression is associated with differential promoter methylation in psychiatric and neurological disorders, our results suggest that different mechanisms take place in AD. The finding that the control of Sirt1 protein levels in blood is not exerted through the repression of mRNA expression by promoter hypermethylation is in agreement with previous data. In contrast, other studies reported that Psen1 methylation may be increased or decreased in AD patients, suggesting that additional studies are required. In conclusion, this study shows that peripheral levels of the potential AD biomarker proteins Bdnf, Sirt1, and Psen1 are not regulated by different promoter methylation. PMID- 26275348 TI - Effects of environmental enrichment during induction of methamphetamine dependence on the behavioral withdrawal symptoms in rats. AB - This study was designed to examine the effect of environmental enrichment during METH administration on the behavioral withdrawal symptoms after drug abstinence in rats. Rats reared in standard (SE) or enriched environment (EE) during induction of METH dependence with bi-daily injections of METH (2mg/kg, at 12-h. intervals) for 14 days. Then, rats were evaluated for behavioral withdrawal symptoms, and also for anxiety (elevated plus maze-EPM) and depression (Forced swim test-FST) over a ten day period of abstinence. The results showed that stereotypic behaviors score and the number of rearing were significantly lower in METH/EE rats compared to the SE group during 1-4 days. Also, The METH/EE group exhibited more weight gain during 6-10 days of abstinence. The METH/EE rats exhibited lower levels of immobility after METH abstinence than control group in the FST. EE had no effect on anxiety-like behavior. This study showed that exposure to EE diminished the severity of withdrawal symptoms and depressive-like behavior during spontaneous withdrawal from METH. PMID- 26275349 TI - Involvement of the dopaminergic system in the central orexin-induced antinociceptive action against colonic distension in conscious rats. AB - We have recently demonstrated that orexin acts centrally in the brain to induce antinociceptive action against colonic distension through orexin 1 receptors in conscious rats. Although the dopaminergic system can induce antinociceptive action for somatic pain, the association between changes in the dopaminergic system and visceral pain perception has not been investigated. In the present study, we hypothesized that the dopaminergic system may be involved in visceral nociception, and if so, the dopaminergic system may mediate the orexin-induced visceral antinociception. Visceral sensation was evaluated using the colonic distension-induced abdominal withdrawal reflex (AWR) in conscious rats. Intracisternal injection of D1 (SKF38398) or D2 (quinpirole) dopamine receptor agonist increased the threshold volume of colonic distension-induced AWR in a dose-dependent manner. Pretreatment with either the D1 or D2 dopamine receptor antagonist (SCH23390 or sulpiride, respectively) potently blocked the centrally injected orexin-A-induced antinociceptive action against colonic distension. These results suggest for the first time that dopaminergic signaling via D1 and D2 dopamine receptors in the brain may induce visceral antinociception and that the dopaminergic signaling may be involved in the central orexin-induced antinociceptive action against colonic distension. PMID- 26275351 TI - Tannic acid functionalized graphene hydrogel for entrapping gold nanoparticles with high catalytic performance toward dye reduction. AB - In this work, a simple, cost-effective, and environmental-friendly strategy was developed to synthesize gold nanoparticles (Au NPs) decorated graphene hydrogel with the use of tannic acid. This facile route involved the reduction of graphene oxide (GO) in the presence of tannic acid to form tannic acid functionalized graphene hydrogel, followed by loading and in situ reduction of AuCl4(-) ions in the graphene hydrogel network benefiting from the abundant phenol groups of tannic acid. Tannic acid (TA), a typical plant polyphenol widely present in woods, not only reduced GO and induced the self-assembly of reduced graphene oxide into graphene hydrogel, but also served as the reducing agent and stabilizer for the synthesis and immobilization of Au NPs, avoiding extra chemical reagent and any stabilizer. The obtained Au NPs decorated graphene hydrogel (Au@TA-GH) was fully characterized and exhibited much higher catalytic activities than the unsupported and other polymer-supported Au NPs toward the reduction of methylene blue (MB). In addition, the high catalytic activity of Au@TA-GH could withhold in different pH solution conditions. Another distinct advantage of Au@TA-GH as catalysts is that it can be easily recovered and reused for five cycles. PMID- 26275350 TI - The nuclear localization pattern and interaction partners of GTF2IRD1 demonstrate a role in chromatin regulation. AB - GTF2IRD1 is one of the three members of the GTF2I gene family, clustered on chromosome 7 within a 1.8 Mb region that is prone to duplications and deletions in humans. Hemizygous deletions cause Williams-Beuren syndrome (WBS) and duplications cause WBS duplication syndrome. These copy number variations disturb a variety of developmental systems and neurological functions. Human mapping data and analyses of knockout mice show that GTF2IRD1 and GTF2I underpin the craniofacial abnormalities, mental retardation, visuospatial deficits and hypersociability of WBS. However, the cellular role of the GTF2IRD1 protein is poorly understood due to its very low abundance and a paucity of reagents. Here, for the first time, we show that endogenous GTF2IRD1 has a punctate pattern in the nuclei of cultured human cell lines and neurons. To probe the functional relationships of GTF2IRD1 in an unbiased manner, yeast two-hybrid libraries were screened, isolating 38 novel interaction partners, which were validated in mammalian cell lines. These relationships illustrate GTF2IRD1 function, as the isolated partners are mostly involved in chromatin modification and transcriptional regulation, whilst others indicate an unexpected role in connection with the primary cilium. Mapping of the sites of protein interaction also indicates key features regarding the evolution of the GTF2IRD1 protein. These data provide a visual and molecular basis for GTF2IRD1 nuclear function that will lead to an understanding of its role in brain, behaviour and human disease. PMID- 26275352 TI - Mercury speciation during in situ thermal desorption in soil. AB - Metallic mercury (Hg(0)) and its compounds are highly mobile and toxic environmental pollutants at trace level. In situ thermal desorption (ISTD) is one of the soil remediation processes applying heat and vacuum simultaneously. Knowledge of thermodynamic mercury speciation is imperative to understand the fate and transport of mercury during thermal remediation and operate the treatment processes in a cost-effective manner. Hence, speciation model for inorganic mercury was developed over a range of environmental conditions to identify distribution of dissolved mercury species and potential transformations of mercury at near source environment. Simulation of phase transitions for metallic mercury, mercury(II) chloride and mercury sulfide with temperature increase showed that complete vaporization of metallic mercury and mercury(II) chloride were achieved below the boiling point of water. The effect of soil compositions on mercury removal was also evaluated to better understand thermal remediation process. Higher vapor pressures expected both from soil pore water and inorganic carbonate minerals in soil as well as creation of permeability were significant for complete vaporization and removal of mercury. PMID- 26275353 TI - Variation in childbirth services in California: a cross-sectional survey of childbirth hospitals. AB - OBJECTIVE: The objective of the study was to describe the resources and activities associated with childbirth services. STUDY DESIGN: We adapted models for assessing the quality of healthcare to generate a conceptual framework hypothesizing that childbirth hospital resources and activities contributed to maternal and neonatal outcomes. We used this framework to guide development of a survey, which we administered by telephone to hospital labor and delivery nurse managers in California. We describe the findings by hospital type (ie, integrated delivery system [IDS], teaching, and other [community] hospitals). RESULTS: Of 248 nonmilitary childbirth hospitals in California, 239 (96%)responded; 187 community, 27 teaching, and 25 IDS hospitals reported. The context of services varied across hospital types, with community hospitals more likely to have for profit ownership, be in a rural or isolated location, and have fewer annual deliveries per hospital. Results included the findings of the following: (1) 24 hour anesthesia availability in 50% of community vs 100% of IDS and teaching hospitals (P < .001); (2) 24 hour in-house labor and delivery physician coverage in 5% of community vs 100% of IDS and 48% of teaching hospitals (P < .001); (3) 24 hour blood bank availability in 88% of community vs 96% of IDS and 100% of teaching hospitals (P = .092); (4) adult subspecialty intensive care unit availability in 33% of community vs 36% of IDS and 82% of teaching hospitals (P < .001); (5) ability to perform emergency cesarean delivery in 30 minutes 100% of the time in 56% of community vs 100% of IDS and 85% of teaching hospitals (P < .001); (6) pediatric care available both day and night in 54% of community vs 63% of IDS vs 76% of teaching hospitals (P = .087); and (7) no neonatal intensive care unit in 44% of community vs 12% of IDS and 4% of teaching hospitals (P < .001). CONCLUSION: Childbirth services varied widely across California hospitals. Cognizance of this variation and linkage of these data to childbirth outcomes should assist in the identification of key resources and activities that optimize the hospital environment for pregnant women and set the groundwork for identifying criteria for the provision of maternal risk-appropriate care. PMID- 26275354 TI - Does 17-alpha hydroxyprogesterone caproate prevent recurrent preterm birth in obese women? AB - OBJECTIVE: We sought to determine if maternal weight or body mass index (BMI) modifies the effectiveness of 17-alpha hydroxyprogesterone caproate (17OHP-C). STUDY DESIGN: We performed a secondary analysis of the Maternal-Fetal Medicine Units Network Trial for the Prevention of Recurrent Preterm Delivery by 17-Alpha Hydroxyprogesterone Caproate. Binomial regression models were estimated to determine the relative risk (RR) of preterm birth (PTB) in women randomized to 17OHP-C vs placebo according to BMI category and maternal weight. Adjusted models considered inclusion of potential confounders. RESULTS: In all, 443 women with complete data were included. 17OHP-C is effective in preventing PTB <37 weeks only in women with prepregnancy BMI <30 kg/m(2) (RR, 0.54; 95% confidence interval, 0.43-0.68). Above this BMI threshold there is a nonsignificant trend toward an increased risk of PTB (RR, 1.55; 95% confidence interval, 0.83-2.89) with 17OHP-C treatment. When analyzing by maternal weight, a similar threshold is observed at 165 lb, above which 17OHP-C is no longer effective. CONCLUSION: The effectiveness of 17OHP-C is modified by maternal weight and BMI, and treatment does not appear to reduce the rate of PTB in women who are obese or have a weight >165 lb. This finding may be due to subtherapeutic serum levels in women with increased BMI or weight. Studies of adjusted-dose 17OHP-C in women who are obese or who weigh >165 lb are warranted, and current recommendations regarding the uniform use of 17OHP-C regardless of maternal BMI and weight may deserve reassessment. PMID- 26275355 TI - hERG potassium channel inhibition by ivabradine requires channel gating. PMID- 26275356 TI - Smoking and risk for psoriasis: a population-based twin study. AB - BACKGROUND: Smoking is a potential risk factor for psoriasis. Both psoriasis and smoking habits are partly explained by genetic factors. However, twin studies investigating the association between these traits are limited. METHODS: Questionnaire-based data on smoking habits and psoriasis were collected for 34,781 twins, aged 20-71 years, from the Danish Twin Registry. A co-twin control analysis was performed on 1700 twin pairs discordant for lifetime history of smoking. Genetic and environmental correlations between smoking and psoriasis were estimated using classical twin modeling. RESULTS: After multivariable adjustment, age group (50-71 vs. 20-49 years) and childhood exposure to environmental tobacco smoke (ETS) were significantly associated with psoriasis in the whole population (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.02 1.29 [P = 0.021] and OR 1.28, 95% CI 1.10-1.49 [P = 0.002], respectively). Risk for psoriasis increased substantially (OR 2.18, 95% CI 1.82-2.61; P < 0.001) for smokers with a history of >5 pack-years, even after adjusting for age, sex, and childhood ETS. Among twin pairs discordant for smoking, risk for psoriasis in the ever-smoking twin was lower among monozygotic twins (OR 1.23, 95% CI 0.59-2.56; P = 0.578) than among same-sex dizygotic twins (OR 2.21, 95% CI 1.36-3.58; P = 0.001). Genetic factors explained 20% (14-25%; P < 0.001) of the correlation between psoriasis and smoking, whereas non-shared environmental factors explained 8% (0-22%; P = 0.504). CONCLUSIONS: Tobacco consumption and childhood ETS are significantly associated with psoriasis. Results indicate shared genetic factors for smoking and psoriasis. PMID- 26275357 TI - Search for a Symmetrical C-F-C Fluoronium Ion in Solution: Kinetic Isotope Effects, Synthetic Labeling, and Computational, Solvent, and Rate Studies. AB - Recently, we reported evidence for the generation of a symmetrical fluoronium ion (a [C-F-C](+) interaction) in solution from a cage-like precursor, relying heavily on a single isotopic-labeling experiment. Paraphrasing the axiom that a strong claim must be met by as much evidence as possible, we seek to expand upon our initial findings with comprehensive labeling studies, rate measurements, kinetic isotope effect (KIE) experiments, synthetic studies, and computations. We also chronicle the development of the system, our thought process, and how it evolved from a tantalizing indication of fluoronium ion assistance in a dibromination reaction to the final, optimized system. Our experiments show secondary KIE experiments that are fully consistent with a transition state involving fluorine participation; this is also confirmed by a significant remote isotope effect. Paired with DFT calculations, the KIE experiments are indicative of the trapping of a symmetrical intermediate. Additionally, starting with an epimeric in-triflate precursor that hydrolyzes through a putative frontside SNi mechanism involving fluorine participation, KIE studies indicate that an identical intermediate is trapped (the fluoronium ion). Studies also show that the rate-determining step of the fluoronium forming SN1 reaction can be changed on the basis of solvent and additives. We also report the synthesis of a nonfluorinated control substrate to measure a relative anchimeric role of the fluorine atom in hydrolysis versus MU-hydrido bridging. After extensive testing, we can make the remarkable conclusion that our system reacts solely through a "tunable" SN1 mechanism involving a fluoronium ion intermediate. Alternative scenarios, such as SN2 reactivity, do not occur even under forced conditions where they should be highly favored. PMID- 26275358 TI - Serum BDNF as a peripheral biomarker of treatment-resistant depression and the rapid antidepressant response: A comparison of ketamine and ECT. AB - BACKGROUND: Ketamine is associated with rapid antidepressant efficacy but the biological mechanisms underpinning this effect are unclear. Serum brain-derived neurotrophic factor (sBDNF) is a potential circulating biomarker of treatment resistant depression (TRD) and ketamine response but it is unclear if this is a common target of both ketamine and electroconvulsive therapy (ECT), the current gold standard for TRD. Moreover, the impact of multiple ketamine infusions on sBDNF has not yet been established. METHODS: Thirty five TRD patients with a current DSM-IV diagnosis of recurrent depressive disorder received up to 12 ECT sessions (N=17) or up to three intravenous infusions of low-dose (0.5mg/kg) ketamine (N=18). Blood samples were taken over the course of the study for assessment of sBDNF. Symptom severity and response were monitored using the 17 item Hamilton Depression Rating Scale (HDRS). sBDNF was assessed in 20 healthy controls to allow comparison with TRD patients. RESULTS: As expected, sBDNF was lower in TRD patients at baseline compared to healthy controls. Ketamine and ECT treatment were both associated with significant reductions in depressive symptoms. However, sBDNF was significantly elevated only at one week following the first ketamine infusion in those classified as responders one week later. sBDNF was not elevated following subsequent infusions. ECT reduced depressive symptoms, as expected, but was not associated with an enhancement in BDNF. LIMITATIONS: Patients continued with their psychotropic medications throughout this trial. CONCLUSIONS: SBDNF normalisation does not appear to be a prerequisite for symptomatic improvement in TRD following ketamine or ECT treatment. PMID- 26275359 TI - Adolescent coping profiles differentiate reports of depression and anxiety symptoms. AB - The purpose of the study was to identify groups of adolescents based on their reported use of different coping strategies and compare levels of depression and anxiety symptoms across the groups. Tenth and eleventh grade public school students (N=982; 51% girls; 66% Caucasian; M age=16.04, SD=0.73) completed a battery of self-report measures that assessed their use of different coping strategies, depressive symptoms, and anxiety symptoms. Latent profile analysis (LPA) classified the participants into four distinct groups based on their responses on subscales of the COPE inventory (Carver et al., 1989). Groups differed in amount of coping with participants in each group showing relative preference for engaging in certain strategies over others. Disengaged copers reported the lowest amounts of coping with a preference for avoidance strategies. Independent copers reported moderate levels of coping with relatively less use of support-seeking. Social support-seeking copers and active copers reported the highest levels of coping with a particular preference for support-seeking strategies. The independent copers reported the lowest levels of depressive symptoms compared to the three other groups. The Social Support Seeking and Active Coping Groups reported the highest levels of anxiety. Although distinct coping profiles were observed, findings showed that adolescents between the ages of 14 and 16 engage in multiple coping strategies and are more likely to vary in their amount of coping than in their use of specific strategies. PMID- 26275360 TI - Examining reward-seeking, negative self-beliefs and over-general autobiographical memory as mechanisms of change in classroom prevention programs for adolescent depression. AB - BACKGROUND: Effective methods to prevent adolescent depressive symptoms could reduce suffering and burden across the lifespan. However, psychological interventions delivered to adolescents show efficacy only in symptomatic or high risk youth. Targeting causal risk factors and assessing mechanistic change can help devise efficacious universal or classroom based prevention programs. METHODS: A non-randomized longitudinal design was used to compare three classroom based prevention programs for adolescent depression (Behavioral Activation with Reward Processing, "Thinking about Reward in Young People" (TRY); Cognitive Behavioral Therapy (CBT) and Mindfulness Based Cognitive Therapy (MBCT)), and determine cognitive mechanisms of change in these programs. Cognitive mechanisms examined were reward-seeking, negative self-beliefs (assessed with behavioral tasks) and over-general autobiographical memory. 256 healthy adolescents aged 13 14 participated with 236 (92%) and 227 (89%) completing the pre- and post assessments. RESULTS: TRY was the only intervention associated with a reduction in depressive symptoms at follow-up. Reward-seeking increased following TRY. In the other programs there were non-significant changes in cognitive mechanisms, with more reflective negative self-beliefs in CBT and fewer over-general autobiographical memories in MBCT In the TRY program, which focused on increasing sensitivity to rewarding activities, reward seeking increased and this was associated with decreased depressive symptoms. LIMITATIONS: Due to the infeasibility of a cluster randomized controlled trial, a non-randomized design was used. CONCLUSIONS: Increased reward-seeking was associated with decreased depressive symptoms and may be a mechanism of depressive symptom change in the intervention with a focus on enhancing sensitivity and awareness of reward. This study provides preliminary evidence to suggest that incorporating activities to enhance reward sensitivity may be fruitful in randomized controlled trials of universal prevention programs for depression. PMID- 26275361 TI - Pyrroloquinoline quinone increases the expression and activity of Sirt1 and -3 genes in HepG2 cells. AB - Sirtuin (Sirt) 1 and Sirt 3 are nicotinamide adenine dinucleotide ((+))-dependent protein deacetylases that are important to a number of mitochondrial-related functions; thus, identification of sirtuin activators is important. Herein, we hypothesize that pyrroloquinoline quinone (PQQ) can act as a Sirt1/Sirt3 activator. In HepG2 cell cultures, PQQ increased the expression of Sirt1 and Sirt3 gene, protein, and activity levels (P < .05). We also observed a significant increase in nicotinamide phosphoribosyltransferase gene expression (as early as 18 hours) and increased NAD(+) activity at 24 hours. In addition, targets of Sirt1 and Sirt3 (peroxisome proliferator-activated receptor gamma coactivator 1alpha, nuclear respiratory factor 1 and 2, and mitochondrial transcription factor A) were increased at 48 hours. This is the first report that demonstrates PQQ as an activator of Sirt1 and Sirt3 expression and activity, making it an attractive therapeutic agent for the treatment of metabolic diseases and for healthy aging. Based on our study and the available data in vivo, PQQ has the potential to serve as a therapeutic nutraceutical, when enhancing mitochondrial function. PMID- 26275362 TI - Protective factors for mental health and well-being in a changing climate: Perspectives from Inuit youth in Nunatsiavut, Labrador. AB - The Canadian Arctic is experiencing rapid changes in climatic conditions, with implications for Inuit communities widely documented. Youth have been identified as an at-risk population, with likely impacts on mental health and well-being. This study identifies and characterizes youth-specific protective factors that enhance well-being in light of a rapidly changing climate, and examines how climatic and environmental change challenges these. In-depth conversational interviews were conducted with youth aged 15-25 from the five communities of the Nunatsiavut region of Labrador, Canada: Nain, Hopedale, Postville, Makkovik, and Rigolet. Five key protective factors were identified as enhancing their mental health and well-being: being on the land; connecting to Inuit culture; strong communities; relationships with family and friends; and staying busy. Changing sea ice and weather conditions were widely reported to be compromising these protective factors by reducing access to the land, and increasing the danger of land-based activities. This study contributes to existing work on Northern climate change adaptation by identifying factors that enhance youth resilience and, if incorporated into adaptation strategies, may contribute to creating successful and effective adaptation responses. PMID- 26275363 TI - Direct determination of radionuclides in building materials with self-absorption correction for the 63 and 186 keV gamma-energy lines. AB - The use of 911 keV and 129 keV gamma-line intensity ratio has been applied for self-absorption correction of the 63 keV (234)Th ((238)U) and 186 keV((226)Ra and (235)U) lines in typical building materials and soil samples. Proposed procedure allows to determine (238)U from the (234)Th line (63 keV) and (226)Ra after subtraction of (235)U interference in the 186 keV. It is important in the case of low uranium concentration and weak intensity of (235)U 143 keV gamma energy line, when activity of this radionuclide can be apprised on the natural constant (238)U/(235)U ratio, only (excluding accidental anthropogenic depleted uranium deposition in the soil samples). Therefore, by this method a direct and fast determination of the (226)Ra and other important radionuclides, without one month waiting period for (226)Ra-(222)Rn daughter equilibrium, is possible. The accuracy of the method has been confirmed (relative relation deviation <10%) for typical buildings materials such as: tales, bricks, concrete blocks and various type of ceramic materials. PMID- 26275364 TI - Ultrasonographic demonstration of the superior ophthalmic vein in the orbit of premature infants with and without retinopathy of prematurity. AB - Retinopathy of prematurity (ROP), which develops due to abnormal retinal vascularization in premature babies, can lead to irreversible vision loss. B-scan ocular ultrasonography is a noninvasive examination which makes it possible to image the eye and orbit. Our purpose was to echographically assess the orbit of premature babies with and without retinopathy of prematurity (ROP), with a focus on the superior ophthalmic vein (SOV) which is normally not detected by orbital ultrasound. A prospective study design was used after approved by the local institutional review board. ROP was diagnosed by routine ophthalmoscopic exam. Orbital ultrasound was performed by a single experienced ophthalmologist and ultra-sonographer who was masked to the routine ROP screening results. The results of the ophthalmoscopic exam were compared to the orbital ultrasound findings. The study group was divided into those diagnosed with ROP and those not diagnosed with ROP and were found to be comparable by age and weight at the time of the US examination. The SOV was dilated in 21 of 22 eyes (95.4%) with ROP and in only 5 of 32 eyes (15.6%) without ROP. The present study suggests an association between ROP and dilatation of the SOV. PMID- 26275365 TI - Interval sentinel lymph nodes in melanoma: a digital pathology analysis of Ki67 expression and microvascular density. AB - The presence of interval sentinel lymph nodes in melanoma is documented in several studies, but controversies still exist about the management of these lymph nodes. In this study, an immunohistochemical evaluation of tumor cell proliferation and neo-angiogenesis has been performed with the aim of establishing a correlation between these two parameters between positive and negative interval sentinel lymph nodes. This retrospective study reviewed data of 23 patients diagnosed with melanoma. Bioptic specimens of interval sentinel lymph node were retrieved, and immunohistochemical reactions on tissue sections were performed using Ki67 as a marker of proliferation and CD31 as a blood vessel marker for the study of angiogenesis. The entire stained tissue sections for each case were digitized using Aperio Scanscope Cs whole-slide scanning platform and stored as high-resolution images. Image analysis was carried out on three selected fields of equal area using IHC Nuclear and Microvessel analysis algorithms to determine positive Ki67 nuclei and vessel number. Patients were divided into positive and negative interval sentinel lymph node groups, and the positive interval sentinel lymph node group was further divided into interval positive with micrometastasis and interval positive with macrometastasis subgroups. The analysis revealed a significant difference between positive and negative interval sentinel lymph nodes in the percentage of Ki67-positive nuclei and mean vessel number suggestive of an increased cellular proliferation and angiogenesis in positive interval sentinel lymph nodes. Further analysis in the interval positive lymph node group showed a significant difference between micro- and macrometastasis subgroups in the percentage of Ki67-positive nuclei and mean vessel number. Percentage of Ki67-positive nuclei was increased in the macrometastasis subgroup, while mean vessel number was increased in the micrometastasis subgroup. The results of this study suggest that the correlation between tumor cell proliferation and neo-angiogenesis in interval sentinel lymph nodes in melanoma could be used as a good predictive marker to distinguish interval positive sentinel lymph nodes with micrometastasis from interval positive lymph nodes with macrometastasis subgroups. PMID- 26275366 TI - Delayed leukoencephalopathy of non-small cell lung cancer patients with brain metastases underwent whole brain radiation therapy. AB - To explore the incidence, MR imaging findings, dynamic developing process of delayed leukoencephalopathy (DLE) in non-small cell lung cancer (NSCLC) patients with brain metastases patients who undergone whole brain radiation (WBRT) therapy, we retrospectively reviewed 48 NSCLC patients who underwent WBRT for brain metastases from January 2010 through June 2015 and had evaluable magnetic resonance imaging after treatment. The DLE were graded using a scale to evaluate T2-FLAIR (fluid attenuated image recovery) images: grade 1 = little or no white matter hyperintensity, grade 2 = limited periventricular hyperintensity and grade 3 = diffuse white matter hyperintensity. 48 NSCLC patients with brain metastases were enrolled. The median age of these patients was 55.7 years (range 33-75 years). The median follow-up was 12 months. The characteristic MR imaging of DLE in those patients was bilaterally diffuse white matter T2 hyperintensity around the periventricular areas without enhancement, sparing from U-fiber, callosum and gray matter structure. The incidence of DLE developed 6.25% (3/48), 30.00% (12/40), 48.39% (15/31), 61.90% (13/21), 85.71% (6/7), 100% (3/3) in those patients who were followed up for 3, 6, 9, 12, 24, 36 months, respectively. Through increased understanding of it, it may be possible to help clinicians develop further therapeutic strategies to maximize benefit while limiting potential long term toxicities. These data supplement existing reports regarding the late effects of WBRT in NSCLC patients with brain metastasis. PMID- 26275367 TI - Dynamic contrast enhanced T1 MRI perfusion differentiates pseudoprogression from recurrent glioblastoma. AB - Pseudoprogression may present as transient new or increasing enhancing lesions that mimic recurrent tumors in treated glioblastoma. The purpose of this study was to examine the utility of dynamic contrast enhanced T1 magnetic resonance imaging (DCE MRI) in differentiating between pseudoprogression and tumor progression and devise a cut-off value sensitive for pseudoprogression. We retrospectively examined 37 patients with glioblastoma treated with radiation and temozolomide after surgical resection that then developed new or increasing enhancing lesion(s) indeterminate for pseudoprogression versus progression. Volumetric plasma volume (Vp) and time-dependent leakage constant (Ktrans) maps were measured for the enhancing lesion and the mean and ninetieth percentile histogram values recorded. Lesion outcome was determined by clinical follow up with pseudoprogression defined as stable disease not requiring new treatment. Statistical analysis was performed with Wilcoxon rank-sum tests. Patients with pseudoprogression (n = 13) had Vp (mean) = 2.4 and Vp (90 %tile) = 3.2; and Ktrans (mean) = 3.5 and Ktrans (90 %tile) = 4.2. Patients with tumor progression (n = 24) had Vp (mean) = 5.3 and Vp (90 %tile) = 6.6; and Ktrans (mean) = 7.4 and Ktrans (90 %tile) = 9.1. Compared with tumor progression, pseudoprogression demonstrated lower Vp perfusion values (p = 0.0002) with a Vp (mean) cutoff <3.7 yielding 85% sensitivity and 79% specificity for pseudoprogression. Ktrans (mean) of >3.6 had a 69% sensitivity and 79% specificity for disease progression. DCE MRI shows lower plasma volume and time dependent leakage constant values in pseudoprogression than in tumor progression. A cut-off value with high sensitivity for pseudoprogression can be applied to aid in interpretation of DCE MRI. PMID- 26275368 TI - Optimizing Treatment of Familial Hypercholesterolemia in Children and Adolescents. AB - Cardiovascular disease (CVD) is still the most prominent cause of death and morbidity in the world, and one of the major risk factors for developing CVD is hypercholesterolemia. Familial hypercholesterolemia (FH) is a dominantly inherited disorder characterized by markedly elevated plasma low-density lipoprotein cholesterol and premature coronary heart disease. Currently, several treatment options are available for children with FH. Lifestyle adjustments are the first step in treatment. If this is not sufficient, statins are the preferred initial pharmacological therapy and they have been proven effective and safe. However, treatment goals are often not achieved and, hence, there is a need for novel treatment options. Currently, several options are being studied in adults and first results are promising. However, studies in children are still to be awaited. PMID- 26275369 TI - Immature monocytes recruited to the ischemic mouse brain differentiate into macrophages with features of alternative activation. AB - Acute stroke induces a local inflammatory reaction causing leukocyte infiltration. Circulating monocytes are recruited to the ischemic brain and become tissue macrophages morphologically indistinguishable from reactive microglia. However, monocytes are a heterogeneous population of cells with different functions. Herein, we investigated the infiltration and fate of the monocyte subsets in a mouse model of focal brain ischemia by permanent occlusion of the distal portion of the middle cerebral artery. We separated two main subtypes of CD11b(hi) monocytes according to their expression of the surface markers Ly6C and CD43. Using adoptive transfer of reporter monocytes and monocyte depletion, we identified the pro-inflammatory Ly6C(hi)CD43(lo)CCR2(+) subset as the predominant monocytes recruited to the ischemic tissue. Monocytes were seen in the leptomeninges from where they entered the cortex along the penetrating arterioles. Four days post-ischemia, they had invaded the infarcted core, where they were often located adjacent to blood vessels. At this time, Iba-1(-) and Iba 1(+) cells in the ischemic tissue incorporated BrdU, but BrdU incorporation was rare in the reporter monocytes. The monocyte phenotype progressively changed by down-regulating Ly6C, up-regulating F4/80, expressing low or intermediate levels of Iba-1, and developing macrophage morphology. Moreover, monocytes progressively acquired the expression of typical markers of alternatively activated macrophages, like arginase-1 and YM-1. Collectively, the results show that stroke mobilized immature pro-inflammatory Ly6C(hi)CD43(lo) monocytes that acutely infiltrated the ischemic tissue reaching the core of the lesion. Monocytes differentiated to macrophages with features of alternative activation suggesting possible roles in tissue repair during the sub-acute phase of stroke. PMID- 26275370 TI - Statin-induced calcific Achilles tendinopathy in rats: comparison of biomechanical and histopathological effects of simvastatin, atorvastatin and rosuvastatin. AB - PURPOSE: Accumulating clinical evidence indicates the risk of tendinopathy and spontaneous and/or simultaneous tendon ruptures associated with statin use. This experimental study was designed to evaluate and compare the biomechanical and histopathological effects of the three most commonly prescribed statins (simvastatin, atorvastatin and rosuvastatin) on the Achilles tendon in rats. METHODS: Statins were administered by gavage to rats at daily doses of 20 and 40 mg/kg for 3 weeks. One week later, the Achilles tendons were dissected and their biomechanical properties, including ultimate tensile force, yield force and elastic modulus, were determined. The samples were stained with haematoxylin eosin and examined under a light microscope. The biomechanical properties of the tibia were tested by three-point bending test. Bone mineral density (BMD) and the lengths of tibias were measured by computed tomography. RESULTS: All the statins caused deterioration of the biomechanical parameters of the Achilles tendon. Histopathological analysis demonstrated foci of dystrophic calcification only in the statin-treated groups. However, the number and the total area of calcific deposits were similar between the statin groups. The biomechanical parameters of tibias were improved in all the statin groups. BMD in the statin-treated groups was not significantly different from the control group. CONCLUSION: All the statins tested are associated with calcific tendinopathy risk of which full awareness is required during everyday medical practice. However, statin associated improvement of bone biomechanical properties is a favourable feature which may add to their beneficial effects in atherosclerotic cardiovascular disease, especially in the elderly. PMID- 26275371 TI - Is arthroscopic remplissage a tenodesis or capsulomyodesis? An anatomic study. AB - PURPOSE: Arthroscopic remplissage of a Hill-Sachs lesion is classically described as a capsulotenodesis of the infraspinatus within the posterolateral humeral head. The aim of this cadaveric study was to evaluate the anatomic relationship between the position of anchors and sutures placed for remplissage and the infraspinatus and teres minor. The hypothesis was that remplissage actually corresponds to a capsulomyodesis of the infraspinatus and teres minor muscles. METHODS: A two-anchor arthroscopic remplissage was performed followed by open dissection of ten fresh-frozen human cadaveric shoulders. The exit point of sutures related to muscle-tendon unit as well as the distance between the anchors and the rotator cuff was measured. RESULTS: The superior sutures were localized generally in the infraspinatus, near the musculotendinous junction. The inferior sutures passed through the teres minor muscle in seven of ten cases. The distance between the superior and inferior anchors and the posterolateral greater tuberosity was 14 +/- 2 and 12 +/- 3 mm, respectively. CONCLUSIONS: Arthroscopic remplissage is a capsulomyodesis of infraspinatus and teres minor rather than a capsulotenodesis of the infraspinatus alone as previously believed. Muscular damage may explain posterosuperior pain observed in patients who underwent remplissage. PMID- 26275373 TI - How Van der Waals Interactions Influence the Absorption Spectra of Pheophorbide a Complexes: A Mixed Quantum-Classical Study. AB - The computation of dispersive site energy shifts due to van der Waals interaction (London dispersion forces) was combined with mixed quantum-classical methodology to calculate the linear optical absorption spectra of large pheophorbide a (Pheo) dendrimers. The computed spectra agreed very well with the measurements considering three characteristic optical features occurring with increasing aggregate size: a strong line broadening, a redshift, and a low-energy shoulder. The improved mixed quantum-classical methodology is considered a powerful tool in investigating molecular aggregates. PMID- 26275372 TI - Altered stress patterns and increased risk for postpartum depression among low income pregnant women. AB - Postpartum depression (PPD) has been associated with a number of negative maternal and infant health outcomes. Despite these adverse health effects, few studies have prospectively examined patterns of pre- and postnatal stress that may increase a woman's risk for PPD. The current study examined whether the timing of altered salivary cortisol patterns and perceived stress levels during pregnancy and at 3 months postpartum was associated with PPD symptoms among 100 low-income mothers. Higher levels of PPD were found among women with a lower cortisol awakening response (first and second trimester), lower average daily cortisol (second trimester), a flatter diurnal cortisol pattern (second and third trimester and at 3 months postpartum), and a less abrupt drop in both cortisol and perceived stress from the third trimester to 3 months postpartum. These results support the need for early screening and regulation of stress levels to promote depression prevention efforts in at-risk populations. PMID- 26275374 TI - Neurokinin 1 receptor blockade in the medial amygdala attenuates alcohol drinking in rats with innate anxiety but not in Wistar rats. AB - BACKGROUND AND PURPOSE: Substance P and its preferred neurokinin receptor NK1 have been implicated in stress and anxiety and have been proposed as possible therapeutic targets for the treatment of anxiety/depression. Attention is also being focused on the role this neuropeptide system may play in drug addiction, because stress-related mechanisms promote drug abuse. EXPERIMENTAL APPROACH: The effects of the rat-specific NK1 receptor antagonist, L822429, on alcohol intake and seeking behaviour was investigated in genetically selected Marchigian Sardinian alcohol preferring rats. These rats demonstrate an anxious phenotype and are highly sensitive to stress and stress-induced drinking. KEY RESULTS: Systemic administration of L822429 significantly reduced operant alcohol self administration in Marchigian Sardinian alcohol preferring rats, but did not reduce alcohol self-administration in stock Wistar rats. NK1 receptor antagonism also attenuated yohimbine-induced reinstatement of alcohol seeking at all doses tested but had no effect on cue-induced reinstatement of alcohol seeking. L822429 reduced operant alcohol self-administration when injected into the lateral cerebroventricles or the medial amygdala. L822429 injected into the medial amygdala also significantly reduced anxiety-like behaviour in the elevated plus maze test. No effects on alcohol intake were observed following injection of L822429 into the dorsal or the ventral hippocampus. Conclusions and Implications Our results suggest that NK1 receptor antagonists may be useful for the treatment of alcohol addiction associated with stress or comorbid anxiety disorders. The medial amygdala appears to be an important brain site of action of NK1 receptor antagonism. PMID- 26275376 TI - Alterations in the hepatic transcriptional landscape after RNAi mediated ApoB silencing in cynomolgus monkeys. AB - The greater genomic conservation between humans and non-human primates (NHP) enables target validation studies for developing of therapeutic strategies for human diseases. Together with predicting activity and potential adverse clinical signs, the inclusion of NHP testing bequeaths to efficacy models for dose titration and pharmacodynamic effects. We have used lipid nanoparticle encapsulated siRNA to silence ApoB in the liver and assessed the phenotypic effects on serum lipids with various levels of hepatic ApoB mRNA knockdown in healthy lean cynomolgus monkeys. ApoB siRNA dosed animals demonstrated significant reductions of hepatic ApoB mRNA and serum APOB protein, with a substantial lowering of plasma lipid levels without obvious signs of toxicity. Microarray based assessment of ApoB siRNA mediated effects revealed a number of differentially expressed genes which mapped onto biological pathways and processes related to lipid and cholesterol metabolism. Furthermore, we identified potential targets and cellular effects that could be studied for therapeutic benchmarking of APOB mediated effects. The network of ApoB regulated genes should be of significance for the understanding and development of novel hypercholesterolemia therapies. PMID- 26275375 TI - Carotid atherosclerosis severity in relation to glycemic status: a cross sectional population study. AB - OBJECTIVE: Intima-media thickness (IMT) is increased in subjects with prediabetes or newly diagnosed diabetes. However, no previous studies have evaluated the relationship between the severity of carotid atherosclerosis, assessed by the presence of carotid plaques or stenosis, and the glycemic status, assessed either by fasting glucose, an oral glucose tolerance test (OGTT) or A1C levels. METHODS: Cross-sectional analysis of 1475 subjects (mean age 62 years, 44% males), randomly selected from the population. A fasting blood sample was obtained to determine glucose, lipids, and A1C levels. An OGTT was performed in non-diabetic subjects. Carotid atherosclerosis was evaluated by echo-doppler. RESULTS: A 10.5% of the population had a previous diagnosis of diabetes. Of the 1320 non-diabetic participants, 349 (26.4%) had normal fasting glucose, normal glucose tolerance and A1C < 5.7%, and were considered controls. Prediabetes was diagnosed in 850 subjects (64.4%), and diabetes was newly diagnosed in 121 (9.2%). The prevalence of patients with carotid plaques was 34.2% in controls, 45.1% in prediabetics, 64.2% in newly diagnosed diabetics, and 72.9% in established diabetic patients. These numbers were 0.3%, 1.1%, 5.0% and 7.7% for carotid stenosis, respectively. In multivariate analysis, glycemic status remained significantly associated with the prevalence of carotid plaques after adjusting for age, sex, statin treatment, and cardiovascular risk factors. CONCLUSIONS: Glycemic status is associated with all grades of carotid atherosclerosis, from early signs, as demonstrated by the IMT, to intermediate degrees, as demonstrated by the presence of carotid plaques, to advance atherosclerosis, as established by the presence of carotid stenosis. PMID- 26275378 TI - Laparoscopic ovariectomy by single-port access for ovarian cryopreservation. AB - PURPOSE: The aim of this study is to assess the feasibility of ovariectomy by single-port access laparoscopy for cryopreservation. METHODS: Observational prospective monocentric study including patients referred for an ovariectomy for ovarian tissue cryopreservation underwent ovariectomy by single-port access laparoscopy. Feasibility, intra- and post-operative complications, and quality of the ovarian tissue collected were reported. RESULTS: Height patients were included. No conversion to standard laparoscopy or laparotomy was performed and no intra- or post-operative complications were reported. Median duration of surgery was 35 min (30-60). The quality of all the ovarian tissue collected was correct, and cryopreservation was possible for all patients. CONCLUSIONS: Ovariectomy for cryopreservation by laparoscopy with SPA seems feasible. The advantages of this technique are particularly interesting in these patients who require the least aggressive surgical technique possible and a rapid convalescence. PMID- 26275379 TI - Comment on an article written by Cornelia Bachmann et al. PMID- 26275377 TI - Affective mediators of the association between pleasant events and global sleep quality in community-dwelling adults. AB - This study explored the association of engagement in pleasant events and global sleep quality, as well as examined the intermediary roles of positive affect and depressive symptoms in this association. Data were derived from the Midlife in the United States-II study. The sample consisted of 1054 community-dwelling adults. Participants completed the Pittsburgh Sleep Quality Index and indicated the frequency and enjoyableness of experiences on a positive events scale. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Positive affect was measured using the Mood and Symptoms Questionnaire. Regression analyses indicated more frequent engagement in pleasant events was associated with better global sleep quality. Depressive symptoms, but not positive affect, partially mediated the association between pleasant events and global sleep quality. The findings suggest that behavioral engagement in pleasant events may be related to global sleep quality via depressive symptoms, but not positive affect. These findings highlight the potential for engagement in pleasant activities to influence both mood and sleep. PMID- 26275380 TI - Biglycan enhances the ability of migration and invasion in endometrial cancer. AB - OBJECTIVE: This study aimed to confirm that biglycan (BGN) can promote the migration and invasion in endometrial cancer both in vitro and in vivo and the possible therapeutic value of BGN in endometrial cancer. METHODS: Western blot was used to screen out the higher protein level of BGN in human endometrial cancer cells; BGN knocked down cells were constructed by lentiviral transfection; The effect of BGN in endometrial cancer detected by wound healing, transwell migration, and invasion, endothelial tube formation assay in vitro, and xenograft model in vivo. RESULTS: (1) We found that BGN expression level is higher in the Ishikawa (ISK, high differentiation) and AN3CA (poor differentiation) cells than other endometrial cancer cells. (2) BGN enhances endometrial cancer cell wound healing, invasion, and migration ability and formation ability of endothelial cells in vitro. Xenograft model has confirmed the outcome in vivo. CONCLUSIONS: BGN might play an important role on metastasis in human endometrial cancer and it might be a target marker for the molecular therapy of advanced and recurrence endometrial cancer. PMID- 26275381 TI - Intra-abdominal adhesions: vaginal or abdominal delivery? PMID- 26275382 TI - The left amygdala: A shared substrate of alexithymia and empathy. AB - Alexithymia, a deficit in emotional self-awareness, and deficits in empathy, which encompasses the awareness of other's emotions, are related constructs that are both associated with a range of psychopathological disorders. Neuroimaging studies suggest that there is overlap between the neural bases of alexithymia and empathy, but no systematic comparison has been conducted so far. The aim of this structural magnetic resonance imaging study was to disentangle the overlap and differences between the morphological profiles of the cognitive and affective dimensions of alexithymia and empathy, and to find out to what extent these differ between women and men. High-resolution T1 anatomical images were obtained from 125 healthy right-handers (18-42 years), 70 women and 55 men. By means of voxel-based morphometry, region of interest (ROI) analyses were performed on gray matter volumes of several anatomically defined a-priori regions previously linked to alexithymia and empathy. Partial correlations were conducted within the female and male group using ROI parameter estimates as dependent variables and the cognitive and affective dimensions of alexithymia and empathy, respectively, as predictors, controlling for age. Results were considered significant if they survived Holm-Bonferroni correction for multiple comparisons. The left amygdala was identified as a key substrate of both alexithymia and empathy. This association was characterized by an opposite pattern: The cognitive alexithymia dimension was linked to smaller, the two empathy dimensions to larger left amygdala volume. While sex-specific effects were not observed for empathy, they were evident for the affective alexithymia dimension: Men-but not women-with difficulty fantasizing had smaller gray matter volume in the middle cingulate cortex. Moreover, structural covariance patterns between the left amygdala and other emotion-related brain regions differed markedly between alexithymia and empathy. These differences may underlie the complex patterns of deficits in emotional self- and other-awareness observed across a range of psychopathological conditions. PMID- 26275384 TI - Neuroanatomy of intergroup bias: A white matter microstructure study of individual differences. AB - Intergroup bias-the tendency to behave more positively toward an ingroup member than an outgroup member-is a powerful social force, for good and ill. Although it is widely demonstrated, intergroup bias is not universal, as it is characterized by significant individual differences. Recently, attention has begun to turn to whether neuroanatomy might explain these individual differences in intergroup bias. However, no research to date has examined whether white matter microstructure could help determine differences in behavior toward ingroup and outgroup members. In the current research, we examine intergroup bias with the third-party punishment paradigm and white matter integrity and connectivity strength as determined by diffusion tensor imaging (DTI). We found that both increased white matter integrity at the right temporal-parietal junction (TPJ) and connectivity strength between the right TPJ and the dorsomedial prefrontal cortex (DMPFC) were associated with increased impartiality in the third-party punishment paradigm, i.e., reduced intergroup bias. Further, consistent with the role that these brain regions play in the mentalizing network, we found that these effects were mediated by mentalizing processes. Participants with greater white matter integrity at the right TPJ and connectivity strength between the right TPJ and the DMPFC employed mentalizing processes more equally for ingroup and outgroup members, and this non-biased use of mentalizing was associated with increased impartiality. The current results help shed light on the mechanisms of bias and, potentially, on interventions that promote impartiality over intergroup bias. PMID- 26275385 TI - Cortisol awakening response predicts intrinsic functional connectivity of the medial prefrontal cortex in the afternoon of the same day. AB - Cortisol awakening response (CAR) is the cortisol secretory activity in the first 30-60 min immediately after awakening in the morning. Alterations in CAR as a trait have been associated with changes in the brain structure and function. CAR also fluctuates over days. Little, however, is known about the relationship between CAR as a state and brain activity. Using resting-state functional magnetic resonance imaging (fMRI), we investigated whether the CAR predicts intrinsic functional connectivity (FC) of the brain in the afternoon of the same day. Data from forty-nine healthy participants were analyzed. Salivary cortisol levels were assessed immediately after awakening and 15, 30 and 60 min after awakening, and resting-state fMRI data were obtained in the afternoon. Global FC strength (FCS) of each voxel was computed to provide a whole-brain characterization of intrinsic functional architecture. Correlation analysis was used to examine whether CAR predicts the intrinsic FC of core brain networks. We observed that the CAR was positively correlated with the FCS of the medial prefrontal cortex (mPFC). Further analysis revealed that higher CAR predicted stronger positive mPFC connectivity with regions in the default mode network. Our findings suggest that the HPA activity after awakening in the early morning may predict intrinsic functional connectivity of mPFC at rest in the afternoon of the same day. PMID- 26275383 TI - Assessing atrophy measurement techniques in dementia: Results from the MIRIAD atrophy challenge. AB - Structural MRI is widely used for investigating brain atrophy in many neurodegenerative disorders, with several research groups developing and publishing techniques to provide quantitative assessments of this longitudinal change. Often techniques are compared through computation of required sample size estimates for future clinical trials. However interpretation of such comparisons is rendered complex because, despite using the same publicly available cohorts, the various techniques have been assessed with different data exclusions and different statistical analysis models. We created the MIRIAD atrophy challenge in order to test various capabilities of atrophy measurement techniques. The data consisted of 69 subjects (46 Alzheimer's disease, 23 control) who were scanned multiple (up to twelve) times at nine visits over a follow-up period of one to two years, resulting in 708 total image sets. Nine participating groups from 6 countries completed the challenge by providing volumetric measurements of key structures (whole brain, lateral ventricle, left and right hippocampi) for each dataset and atrophy measurements of these structures for each time point pair (both forward and backward) of a given subject. From these results, we formally compared techniques using exactly the same dataset. First, we assessed the repeatability of each technique using rates obtained from short intervals where no measurable atrophy is expected. For those measures that provided direct measures of atrophy between pairs of images, we also assessed symmetry and transitivity. Then, we performed a statistical analysis in a consistent manner using linear mixed effect models. The models, one for repeated measures of volume made at multiple time-points and a second for repeated "direct" measures of change in brain volume, appropriately allowed for the correlation between measures made on the same subject and were shown to fit the data well. From these models, we obtained estimates of the distribution of atrophy rates in the Alzheimer's disease (AD) and control groups and of required sample sizes to detect a 25% treatment effect, in relation to healthy ageing, with 95% significance and 80% power over follow-up periods of 6, 12, and 24months. Uncertainty in these estimates, and head-to-head comparisons between techniques, were carried out using the bootstrap. The lateral ventricles provided the most stable measurements, followed by the brain. The hippocampi had much more variability across participants, likely because of differences in segmentation protocol and less distinct boundaries. Most methods showed no indication of bias based on the short-term interval results, and direct measures provided good consistency in terms of symmetry and transitivity. The resulting annualized rates of change derived from the model ranged from, for whole brain: -1.4% to -2.2% (AD) and -0.35% to -0.67% (control), for ventricles: 4.6% to 10.2% (AD) and 1.2% to 3.4% (control), and for hippocampi: -1.5% to -7.0% (AD) and -0.4% to -1.4% (control). There were large and statistically significant differences in the sample size requirements between many of the techniques. The lowest sample sizes for each of these structures, for a trial with a 12month follow-up period, were 242 (95% CI: 154 to 422) for whole brain, 168 (95% CI: 112 to 282) for ventricles, 190 (95% CI: 146 to 268) for left hippocampi, and 158 (95% CI: 116 to 228) for right hippocampi. This analysis represents one of the most extensive statistical comparisons of a large number of different atrophy measurement techniques from around the globe. The challenge data will remain online and publicly available so that other groups can assess their methods. PMID- 26275386 TI - [Anesthesia management in implantation of baroreceptor stimulators]. AB - Baroreceptor stimulators are novel implantable devices that activate the carotid baroreceptor reflex. This results in a decrease in activity of the sympathetic nervous system and inhibition of the renin-angiotensin-aldosterone system. In patients with drug-resistant hypertension, permanent electrical activation of the baroreceptor reflex results in blood pressure reduction and cardiac remodeling. For correct intraoperative electrode placement at the carotid bifurcation, the baroreceptor reflex needs to be activated several times. Many common anesthetic agents, such as inhalation anesthetics and propofol dampen or inhibit the baroreceptor reflex and complicate or even prevent successful placement. Therefore, a specific anesthesia and pharmacological management is necessary to ensure successful implantation of baroreceptor reflex stimulators. PMID- 26275388 TI - The use of compressive sensing and peak detection in the reconstruction of microtubules length time series in the process of dynamic instability. AB - Microtubules (MTs) are intra-cellular cylindrical protein filaments. They exhibit a unique phenomenon of stochastic growth and shrinkage, called dynamic instability. In this paper, we introduce a theoretical framework for applying Compressive Sensing (CS) to the sampled data of the microtubule length in the process of dynamic instability. To reduce data density and reconstruct the original signal with relatively low sampling rates, we have applied CS to experimental MT lament length time series modeled as a Dichotomous Markov Noise (DMN). The results show that using CS along with the wavelet transform significantly reduces the recovery errors comparing in the absence of wavelet transform, especially in the low and the medium sampling rates. In a sampling rate ranging from 0.2 to 0.5, the Root-Mean-Squared Error (RMSE) decreases by approximately 3 times and between 0.5 and 1, RMSE is small. We also apply a peak detection technique to the wavelet coefficients to detect and closely approximate the growth and shrinkage of MTs for computing the essential dynamic instability parameters, i.e., transition frequencies and specially growth and shrinkage rates. The results show that using compressed sensing along with the peak detection technique and wavelet transform in sampling rates reduces the recovery errors for the parameters. PMID- 26275389 TI - Performance comparison of multi-label learning algorithms on clinical data for chronic diseases. AB - We are motivated by the issue of classifying diseases of chronically ill patients to assist physicians in their everyday work. Our goal is to provide a performance comparison of state-of-the-art multi-label learning algorithms for the analysis of multivariate sequential clinical data from medical records of patients affected by chronic diseases. As a matter of fact, the multi-label learning approach appears to be a good candidate for modeling overlapped medical conditions, specific to chronically ill patients. With the availability of such comparison study, the evaluation of new algorithms should be enhanced. According to the method, we choose a summary statistics approach for the processing of the sequential clinical data, so that the extracted features maintain an interpretable link to their corresponding medical records. The publicly available MIMIC-II dataset, which contains more than 19,000 patients with chronic diseases, is used in this study. For the comparison we selected the following multi-label algorithms: ML-kNN, AdaBoostMH, binary relevance, classifier chains, HOMER and RAkEL. Regarding the results, binary relevance approaches, despite their elementary design and their independence assumption concerning the chronic illnesses, perform optimally in most scenarios, in particular for the detection of relevant diseases. In addition, binary relevance approaches scale up to large dataset and are easy to learn. However, the RAkEL algorithm, despite its scalability problems when it is confronted to large dataset, performs well in the scenario which consists of the ranking of the labels according to the dominant disease of the patient. PMID- 26275387 TI - Comparative study of 18F-FDG-PET/CT imaging and serum hTERT mRNA quantification in cancer diagnosis. AB - We have reported on the clinical usefulness of human telomerase reverse transcriptase (hTERT) mRNA quantification in sera in patients with several cancers. Positron emission tomography-computed tomography (PET/CT) using 18F fluorodeoxyglucose (FDG) has recently become an excellent modality for detecting cancer. We performed a diagnostic comparative study of FDG-PET/CT and hTERT mRNA quantification in patients with cancer. Four hundred seventy subjects, including 125 healthy individuals and 345 outpatients with cancer who had received medical treatments for cancer in their own or other hospitals, were enrolled. The subjects were diagnosed by FDG-PET/CT, and we measured their serum hTERT mRNA levels using real-time RT-PCR, correlating the quantified values with the clinical course. In this prospective study, we statistically assessed the sensitivity and specificity, and their clinical significance. hTERT mRNA and FDG PET/CT were demonstrated to be correlated with the clinical parameters of metastasis and recurrence (P < 0.001), and of recurrence and tumor number in cancer compared with noncancer patients, respectively. A multivariate analysis showed a significant difference in the detection by FDG-PET/CT, 18F-FDG uptake, the detection by hTERT mRNA, and age. The use of both FDG-PET/CT and hTERT mRNA resulted in a positivity of 94.4% (221/234) for the detection of viable tumor cells. FDG-PET/CT is superior to hTERT mRNA quantification in the early detection of cancer and combinative use of FDG-PET/CT and hTERT mRNA may improve the diagnostic accuracy of cancer. PMID- 26275390 TI - A case of penetration of the intestinal wall by a soft-shelled turtle bone successfully removed with double-balloon endoscopy. AB - A 62-year-old male was admitted to our hospital due to left lower abdominal pain. Three days before admission, he ate seafood in a Japanese restaurant. Two days before admission, he suffered from intermittent left lower abdominal pain. One day before admission, he developed a high fever and subsequently visited our hospital the following day. Localized tenderness and rebound pain were observed in the left lower abdomen, and C-reactive protein was elevated. Computed tomography revealed a linear high-density object in the distal portion of the small intestine accompanied by edema of the wall, suggesting penetration by something like a fishbone. On the ninth hospital day, double-balloon endoscopy was performed via the transanal route. Yellow foreign material was found in the ileum and was then successfully removed with biopsy forceps. The removed material measured 3 mm in width, 3 cm in length and was slightly curved. It proved to be a bone of the forefoot of a soft-shelled turtle, which had been included on the menu of the restaurant. The patient was completely cured and discharged on the 14th hospital day. PMID- 26275391 TI - Strain-promoted reaction of 1,2,4-triazines with bicyclononynes. AB - Strain-promoted inverse electron-demand Diels-Alder cycloaddition (SPIEDAC) reactions between 1,2,4,5-tetrazines and strained dienophiles, such as bicyclononynes, are among the fastest bioorthogonal reactions. However, the synthesis of 1,2,4,5-tetrazines is complex and can involve volatile reagents. 1,2,4-Triazines also undergo cycloaddition reactions with acyclic and unstrained dienophiles at elevated temperatures, but their reaction with strained alkynes has not been described. We postulated that 1,2,4-triazines would react with strained alkynes at low temperatures and therefore provide an alternative to the tetrazine cycloaddition reaction for use in in vitro or in vivo labelling experiments. We describe the synthesis of a 1,2,4-triazin-3-ylalanine derivative fully compatible with the fluorenylmethyloxycarbonyl (Fmoc) strategy for peptide synthesis and demonstrate its reaction with strained bicyclononynes at 37 degrees C with rates comparable to the reaction of azides with the same substrates. The synthetic route to triazinylalanine is readily adaptable to late stage functionalization of other probe molecules, and the 1,2,4-triazine-SPIEDAC therefore has potential as an alternative to tetrazine cycloaddition for applications in cellular and biochemical studies. PMID- 26275393 TI - The Size But not the Symmetry of the Wings of Eulaema nigrita Lepeletier (Apidae: Euglossini) is Affected by Human-Disturbed Landscapes in the Brazilian Cerrado Savanna. AB - Among other human-related activities, habitat loss and fragmentation are currently ranked as the most important environmental features affecting the persistence of animal and plant populations in landscapes, as well as the maintenance of ecological processes and services. Since these processes are also capable of affecting the ontogenetic development of species inhabiting those landscapes, here we measured the wing veins of male Eulaema nigrita Lepeletier (Apidae: Euglossini) bees in order to evaluate whether the bees sampled in agriculture (AG) areas suffer higher fluctuating asymmetry (FA) than those sampled in Cerrado (CE) areas in the Brazilian state of Goias. We believe that individuals sampled in CE areas would be less asymmetric than those sampled in AG areas, given a potential higher exposure of these specimens to environmental stresses (mostly pesticides). However, we did not observe a significant trend in the FA measures we obtained, although three wing measures were bigger for bees from CE areas. The lack of significant effects of FA may be related to inherent bionomic features of E. nigrita. For instance, given their high individual dispersal abilities, the individuals we analyzed may have developed in different areas than those where they were sampled. Their generalist feeding behavior may also have given them a higher resistance to environmental perturbations, buffering the normal development of immatures even in areas with local high environmental stress. Nonetheless, higher death rates of individuals from anthropic areas may also have killed the developing immatures of E. nigrita before they reached adulthood consequently equalizing our sampled estimates. PMID- 26275392 TI - (99m)Tc-Annexin A5 quantification of apoptotic tumor response: a systematic review and meta-analysis of clinical imaging trials. AB - PURPOSE: (99m)Tc-Annexin A5 has been used as a molecular imaging probe for the visualization, characterization and measurement of apoptosis. In an effort to define the quantitative (99m)Tc-annexin A5 uptake criteria that best predict tumor response to treatment, we performed a systematic review and meta-analysis of the results of all clinical imaging trials found in the literature or publicly available databases. METHODS: Included in this review were 17 clinical trials investigating quantitative (99m)Tc-annexin A5 (qAnx5) imaging using different parameters in cancer patients before and after the first course of chemotherapy and/or radiation therapy. Qualitative assessment of the clinical studies for diagnostic accuracy was performed using the QUADAS-2 criteria. Of these studies, five prospective single-center clinical trials (92 patients in total) were included in the meta-analysis after exclusion of one multicenter clinical trial due to heterogeneity. Pooled positive predictive values (PPV) and pooled negative predictive values (NPV) (with 95% CI) were calculated using Meta-Disc software version 1.4. RESULTS: Absolute quantification and/or relative quantification of (99m)Tc-annexin A5 uptake were performed at baseline and after the start of treatment. Various quantitative parameters have been used for the calculation of (99m)Tc-annexin A5 tumor uptake and delta (Delta) tumor changes post-treatment compared to baseline including: tumor-to-background ratio (TBR), DeltaTBR, tumor to-noise ratio, relative tumor ratio (TR), DeltaTR, standardized tumor uptake ratio (STU), DeltaSTU, maximum count per pixel within the tumor volume (Cmax), Cmax%, absolute DeltaU and percentage (DeltaU%), maximum DeltaU counts, semiquantitative visual scoring, percent injected dose (%ID) and %ID/cm(3). Clinical trials investigating qAnx5 imaging have included patients with lung cancer, lymphoma, breast cancer, head and neck cancer and other less common tumor types. In two phase I/II single-center clinical trials, an increase of >=25% in uptake following treatment was considered a significant threshold for an apoptotic tumor response (partial response, complete response). In three other phase I/II clinical trials, increases of >=28%, >=42% and >=47% in uptake following treatment were found to be the mean cut-off levels in responders. In a phase II/III multicenter clinical trial, an increase of >=23% in uptake following treatment was found to be the minimum cut-off level for a tumor response. In one clinical trial, no significant difference in (99m)Tc-annexin A5 uptake in terms of %ID was found in healthy tissues after chemotherapy compared to baseline. In two other clinical trials, intraobserver and interobserver measurements of (99m)Tc-annexin A5 tumor uptake were found to be reproducible (mean difference <5%, kappa = 0.90 and 0.82, respectively) and to be highly correlated with treatment outcome (Spearman r = 0.99, p < 0.0001). The meta-analysis demonstrated a pooled positive PPV of 100% (95% CI 92 - 100%) and a pooled NPV of 70% (95% CI 55 - 82%) for prediction of a tumor response after the first course of chemotherapy and/or radiotherapy in terms of DeltaU%. In a symmetric sROC analysis, the AUC was 0.919 and the Q* index was 85.21 %. CONCLUSION: Quantitative (99m)Tc-annexin A5 imaging has been investigated in clinical trials for the assessment of apoptotic tumor responses. This meta-analysis showed a high pooled PPV and a moderate pooled NPV with DeltaU cut-off values ranging between 20% and 30%. Standardization of quantification and harmonization of results are required for high-quality clinical research. A standardized uptake value score (SUV, DeltaSUV) using quantitative SPECT/CT imaging may be a promising approach to the simple, reproducible and semiquantitative assessment of apoptotic tumor changes. PMID- 26275394 TI - Crohn associated microbial communities associated to colonic mucosal biopsies in patients of the western Mediterranean. AB - Next generation sequencing approaches allow the retrieval of several orders of magnitude larger numbers of amplified single sequences in 16S rRNA diversity surveys than classical methods. However, the sequences are only partial and thus lack sufficient resolution for a reliable identification. The OPU approach used here, based on a tandem combination of high quality 454 sequences (mean >500 nuc) applying strict OTU thresholds, and phylogenetic inference based on parsimony additions to preexisting trees, seemed to improve the identification yields at the species and genus levels. A total of thirteen biopsies of Crohn-diagnosed patients (CD) and seven healthy controls (HC) were studied. In most of the cases (73%), sequences were affiliated to known species or genera and distinct microbial patterns could be distinguished among the CD subjects, with a common depletion of Clostridia and either an increased presence of Bacteroidetes (CD1) or an anomalous overrepresentation of Proteobacteria (CD2). Faecalibacterium prausnitzii presence was undetectable in CD, whereas Bacteroides vulgatus-B. dorei characterized HC and some CD groups. Altogether, the results showed that a microbial composition with predominance of Clostridia followed by Bacteroidetes, with F. prausnitzii and B. vulgatus-B. dorei as major key bacteria, characterized what could be considered a balanced structure in HC. The depletion of Clostridia seemed to be a common trait in CD. PMID- 26275395 TI - Mercury mobilization and speciation linked to bacterial iron oxide and sulfate reduction: A column study to mimic reactive transfer in an anoxic aquifer. AB - Mercury (Hg) mobility and speciation in subsurface aquifers is directly linked to its surrounding geochemical and microbial environment. The role of bacteria on Hg speciation (i.e., methylation, demethylation and reduction) is well documented, however little data is available on their impact on Hg mobility. The aim of this study was to test if (i) Hg mobility is due to either direct iron oxide reduction by iron reducing bacteria (IRB) or indirect iron reduction by sulfide produced by sulfate reducing bacteria (SRB), and (ii) to investigate its subsequent fate and speciation. Experiments were carried out in an original column setup combining geochemical and microbiological approaches that mimic an aquifer including an interface of iron-rich and iron depleted zones. Two identical glass columns containing iron oxides spiked with Hg(II) were submitted to (i) direct iron reduction by IRB and (ii) to indirect iron reduction by sulfides produced by SRB. Results show that in both columns Hg was leached and methylated during the height of bacterial activity. In the column where IRB are dominant, Hg methylation and leaching from the column was directly correlated to bacterial iron reduction (i.e., Fe(II) release). In opposition, when SRB are dominant, produced sulfide induced indirect iron oxide reduction and rapid adsorption of leached Hg (or produced methylmercury) on neoformed iron sulfides (e.g., Mackinawite) or its precipitation as HgS. At the end of the SRB column experiment, when iron-oxide reduction was complete, filtered Hg and Fe concentrations increased at the outlet suggesting a leaching of Hg bound to FeS colloids that may be a dominant mechanism of Hg transport in aquifer environments. These experimental results highlight different biogeochemical mechanisms that can occur in stratified sub surface aquifers where bacterial activities play a major role on Hg mobility and changes in speciation. PMID- 26275396 TI - Transport of barrel and spherical shaped colloids in unsaturated porous media. AB - Model colloids are usually spherical, but natural colloids have irregular geometries. Transport experiments of spherical colloids may not reflect the transport characteristics of natural colloids in porous media. We investigated saturated and unsaturated transport of colloids with spherical and angular shapes under steady-state, flow conditions. A pulse of negatively-charged colloids was introduced into a silica sand column at three different effective water saturations (Se = 0.31, 0.45, and 1.0). Colloids were introduced under high ionic strength of [106]mM to cause attachment to the secondary energy minimum and later released by changing the pore water to low ionic strength. After the experiment, sand was sampled from different depths (0, -4, and -11 cm) for scanning electron microscopy (SEM) analysis and colloid extraction. Water saturation affected colloid transport with more retention under low than under high saturation. Colloids were retained and released from a secondary energy minimum with more angular-shaped colloids being retained and released. Colloids extracted from the sand revealed highest colloid deposition in the top layer and decreasing deposition with depth. Pore straining and grain-grain wedging dominated colloid retention. PMID- 26275398 TI - Peroxisome Proliferator-Activated Receptor Gamma Promotes Mesenchymal Stem Cells to Express Connexin43 via the Inhibition of TGF-beta1/Smads Signaling in a Rat Model of Myocardial Infarction. AB - BACKGROUND: In this study, we hypothesized that activation of PPAR-gamma enhanced MSCs survival and their therapeutic efficacy via upregulating the expression of Cx43. METHODS: MI was induced in 50 male Sprague-Dawley rats. The rats were randomized into five groups: MI group and four intervention groups, including the MSCs group, combined therapy group (MSCs+ pioglitazone), pioglitazone group and PBS group. Two weeks later, 5 * 10(6) MSCs labeled with PKH26 in PBS were injected into the infarct anterior ventricular free wall in the MSCs and combined therapy groups, and PBS alone was injected into the infarct anterior ventricular free wall in the PBS group. Pioglitazone (3 mg/kg/day) was given to the combined therapy and pioglitazone groups by oral gavage at the same time for another 2 weeks. Myocardial function and relevant signaling molecules involved were all examined thereafter. RESULTS: Heart function was enhanced after MSCs treatment for 2 weeks post MI. A significant improvement of heart function was observed in the combined therapy group in contrast to the other three intervention groups. Compared with the MSCs group, there was a higher level of PPAR-gamma in the combined therapy group; Cx43 was remarkably increased in different regions of the left ventricle; TGF-beta1 was decreased in the infarct zone and border zone. To the downstream signaling molecules, mothers against Smad proteins including Smad2 and Smad3 presented a synchronized alteration with TGF-beta1; no differences of the expressions of ERK1/2 and p38 could be discovered in the left ventricular cardiac tissue. CONCLUSIONS: MSCs transplantation combined with pioglitazone administration improved cardiac function more effectively after MI. Activation of PPAR-gamma could promote MSCs to express Cx43. Inhibition of TGF-beta1/Smads signaling pathway might be involved in the process. PMID- 26275397 TI - Targeting Glioblastoma with the Use of Phytocompounds and Nanoparticles. AB - Glioblastoma multiforme (GBM) are extremely lethal and still poorly treated primary brain tumors, characterized by the presence of highly tumorigenic cancer stem cell (CSC) subpopulations, considered responsible for tumor relapse. In order to successfully eradicate GBM growth and recurrence, new anti-cancer strategies selectively targeting CSCs should be designed. CSCs might be eradicated by targeting some of their cell surface markers and transporters, inducing their differentiation, impacting their hyper-glycolytic metabolism, inhibiting CSC-related signaling pathways and/or by targeting their microenvironmental niche. In this regard, phytocompounds such as curcumin, isothiocyanates, resveratrol and epigallocatechin-3-gallate have been shown to prevent or reverse cancer-related epigenetic dysfunctions, reducing tumorigenesis, preventing metastasis and/or increasing chemotherapy and radiotherapy efficacy. However, the actual bioavailability and metabolic processing of phytocompounds is generally unknown, and the presence of the blood brain barrier often represents a limitation to glioma treatments. Nowadays, nanoparticles (NPs) can be loaded with therapeutic compounds such as phytochemicals, improving their bioavailability and their targeted delivery within the GBM tumor bulk. Moreover, NPs can be designed to increase their tropism and specificity toward CSCs by conjugating their surface with antibodies specific for CSC antigens, with ligands or with glucose analogues. Here we discuss the use of phytochemicals as anti-glioma agents and the applicability of phytochemical-loaded NPs as drug delivery systems to target GBM. Additionally, we provide some examples on how NPs can be specifically formulated to improve CSC targeting. PMID- 26275399 TI - Phylogeny and biogeography of Primula sect. Armerina: implications for plant evolution under climate change and the uplift of the Qinghai-Tibet Plateau. AB - BACKGROUND: The historical orogenesis and associated climatic changes of mountain areas have been suggested to partly account for the occurrence of high levels of biodiversity and endemism. However, their effects on dispersal, differentiation and evolution of many groups of plants are still unknown. In this study, we examined the detailed diversification history of Primula sect. Armerina, and used biogeographic analysis and macro-evolutionary modeling to investigate a series of different questions concerning the evolution of the geographical and ecological distribution of the species in this section. RESULTS: We sequenced five chloroplast and one nuclear genes for species of Primula sect. Armerina. Neither chloroplast nor nuclear trees support the monophyly of the section. The major incongruences between the two trees occur among closely related species and may be explained by hybridization. Our dating analyses based on the chloroplast dataset suggest that this section began to diverge from its relatives around 3.55 million years ago, largely coinciding with the last major uplift of the Qinghai Tibet Plateau (QTP). Biogeographic analysis supports the origin of the section in the Himalayan Mountains and dispersal from the Himalayas to Northeastern QTP, Western QTP and Hengduan Mountains. Furthermore, evolutionary models of ecological niches show that the two P. fasciculata clades have significantly different climatic niche optima and rates of niche evolution, indicating niche evolution under climatic changes and further providing evidence for explaining their biogeographic patterns. CONCLUSION: Our results support the hypothesis that geologic and climatic events play important roles in driving biological diversification of organisms in the QTP area. The Pliocene uplift of the QTP and following climatic changes most likely promoted both the inter- and intraspecific divergence of Primula sect. Armerina. This study also illustrates how niche evolution under climatic changes influences biogeographic patterns. PMID- 26275401 TI - A biomechanical comparison between cortical bone trajectory fixation and pedicle screw fixation. AB - PURPOSE: There have been several reports on the pullout strength of cortical bone trajectory (CBT) screws, but only one study has reviewed the stability of functional spine units using the CBT method. The purpose of this study was to compare vertebral stability after CBT fixation with that after pedicle screw (PS) fixation. METHODS: In this study, 20 lumbar spine (L5-6) specimens were assigned to two groups: the CBT model group that underwent CBT screw fixation (n = 10) and the PS model group that underwent pedicle screw fixation (n = 10). Using a six axis material testing machine, bend and rotation tests were conducted on each model. The angular displacement from the time of no load to the time of maximum torque was defined as range of motion (ROM), and then, the mean ROM in the bend and rotation tests and the mean rate of relative change of ROM in both the bend and rotation tests were compared between the CBT and PS groups. RESULTS: There were no significant differences between the CBT and PS groups with regard to the mean ROMs and the mean rate of relative change of ROMs in both the bend and rotation tests. CONCLUSION: Intervertebral stability after CBT fixation was similar to that after PS fixation. PMID- 26275400 TI - Computational modeling of sphingolipid metabolism. AB - BACKGROUND: As suggested by the origin of the word, sphingolipids are mysterious molecules with various roles in antagonistic cellular processes such as autophagy, apoptosis, proliferation and differentiation. Moreover, sphingolipids have recently been recognized as important messengers in cellular signaling pathways. Notably, sphingolipid metabolism disorders have been observed in various pathological conditions such as cancer and neurodegeneration. RESULTS: The existing formal models of sphingolipid metabolism focus mainly on de novo ceramide synthesis or are limited to biochemical transformations of particular subspecies. Here, we propose the first comprehensive computational model of sphingolipid metabolism in human tissue. Contrary to the previous approaches, we use a model that reflects cell compartmentalization thereby highlighting the differences among individual organelles. CONCLUSIONS: The model that we present here was validated using recently proposed methods of model analysis, allowing to detect the most sensitive and experimentally non-identifiable parameters and determine the main sources of model variance. Moreover, we demonstrate the usefulness of our model in the study of molecular processes underlying Alzheimer's disease, which are associated with sphingolipid metabolism. PMID- 26275402 TI - Pilot study of DNA methylation in the pathogenesis of chronic rhinosinusitis with nasal polyps. AB - BACKGROUND: DNA methylation has been implicated in the pathogenesis of allergy and atopy. This study aimed to identify whether DNA methylation also plays an important role in the pathogenesis of nasal polyps (NP). METHODOLOGY: NP tissues were obtained from 32 patients with chronic rhinosinusitis with bilateral NP. Biopsies of inferior turbinate mucosa (ITM) were taken from 18 patients who underwent rhinoseptoplasty (control group). The methylated genes, which were detected by DNA methylation microarray, were validated by methylation-specific polymerase chain reaction, bisulphite sequencing, real-time polymerase chain reaction and immunohistochemistry. RESULTS: DNA methylation microarray identified 8,008 CpG islands in 2,848 genes. One hundred and ninety-eight genes were found to have a methylated signal in the promoter region in NP samples compared with ITM samples. The four top genes that changed, COL18A1, EP300, GNAS and SMURF1, were selected for further study. The methylation frequency of COL18A1 was significantly higher in NP samples than in ITM samples. CONCLUSIONS: DNA methylation might play an important role in the pathogenesis of NP. Promoter methylation of COL18A1 was found to be significantly increased in NP tissues, further studies are necessary to confirm the significance of these epigenetic factors in the mechanisms underlying the development or persistence of NP. PMID- 26275403 TI - PMSM sensorless control with separate control strategies and smooth switch from low speed to high speed. AB - This paper proposes a smooth switching scheme with separate control strategies on low speed mode and high speed mode for permanent magnet synchronous motor (PMSM) sensorless control to improve the overall performance in full speed range. Constant voltage/frequency tuning method is used on low speed mode because the rotor position can hardly be estimated precisely at low speed. Along with the increasing speed, the control strategy can be switched to high speed mode smoothly when current and speed meet the given requirements. In this high speed mode, the current tracking with a sliding mode observer (SMO) and speed tracking with a sliding mode controller (SMC) are handled, respectively. Experimental demonstration is presented to show the desired performance in full speed range of the PMSM sensorless control using the proposed control scheme in this paper. PMID- 26275404 TI - A novel extended state observer. AB - A novel extended state observer, which feeds back the output estimation error via both nonlinear and switching terms, is put forward for the first time in this paper. No longer neglecting the lumped uncertainty's first time derivative, the problem of disturbance observer design is transformed into the problem of state observer design in the presence of external disturbance. The switching term of the output estimation error is employed to counteract the adverse effect of external disturbance. The newly developed extended state observer provides an attractive solution to the issue of high precision motion control system. Both numerical simulation and experimentation on a speed turntable with temperature box are implemented to verify the performance of the proposed newly developed extended state observer. PMID- 26275405 TI - Comparison of different approaches to estimating age standardized net survival. AB - BACKGROUND: Age-standardized net survival provides an important population-based summary of cancer survival that appropriately accounts for differences in other cause mortality rates and standardizes the population age distribution to allow fair comparisons. Recently, there has been debate over the most appropriate method for estimating this quantity, with the traditional Ederer II approach being shown to have potential bias. METHODS: We compare lifetable-based estimates (Ederer II), a new unbiased method based on inverse probability of censoring weights (Pohar Perme) and model-based estimates. We make the comparison in a simulation setting; generating scenarios where we would expect to see a large theoretical bias. RESULTS: Our simulations demonstrate that even in relatively extreme scenarios there is negligible bias in age-standardized net survival when using the age-standardized Ederer II method, modelling with continuous age or using the Pohar Perme method. However, both the Ederer II and modelling approaches have some advantages over the Pohar Perme method in terms of greater precision, particularly for longer-term follow-up (10 and 15 years). CONCLUSIONS: Our results show that, when age-standardizing, concern over bias with the traditional methods is unfounded. We have also shown advantages in using the more traditional and modelling methods. PMID- 26275406 TI - Platelets, gender and acute cerebral infarction. AB - OBJECTIVE: Platelets may well be significant in the pathogenesis of cerebral infarction. Platelets vary substantially according to gender. The scope of our current work is to establish if female and male stroke sufferers differ regarding platelet reactivity. PATIENTS AND METHODS: 73 Consecutive individuals stricken by acute ischemic cerebral infarction (31 females, 42 males) participated. All stroke subtypes were included. Platelet counts was determined electronically. Platelet reactivity i.e. the presence of surface-bound fibrinogen following provocation was analyzed with a flow cytometer. ADP (1.7 MUmol/L) and a thrombin receptor agonist (TRAP-6) (57 MUmol/L) were the agonists used. RESULTS: Female stroke sufferers had higher platelet counts (p = 0.013) but their platelets were less reactive. The p values were (p = 0.038) and (p = 0.016) for ADP and TRAP-6, respectively. CONCLUSION: The current study demonstrates that women suffering acute cerebral infarction have less reactive platelets. It is concluded that gender affects platelets. Our study indicates that it may be beneficial to individualize platelet inhibition of stroke sufferers according to gender. PMID- 26275407 TI - High-risk percutaneous coronary intervention in a patient with a single coronary artery presenting as STEMI and cardiogenic shock. AB - Cardiogenic shock due to ST elevation myocardial infarction in a patient with a single coronary artery involving the sole vessel is a rare presentation. This can be clinically and angiographically challenging. Proper recognition of the topography of diseased vessels and a systematic guarded approach can lead to procedural success. We report a case of an 81-year-old woman who presented with chest pain followed by a near syncope associated with an acute myocardial infarction. Coronary angiography revealed a single proximally occluded right coronary artery and an anomalous left main coronary artery (originating from the proximal right coronary artery) and occluded distal left circumflex artery. The right coronary artery was successfully stented following predilation without compromising the anomalous left main origin. The flow in the chronically occluded left circumflex artery (originating from the anomalous left main) which was depended on the retrograde supply from right coronary artery through collaterals, was also re-established. PMID- 26275408 TI - Coronary Microembolization Induces Cardiomyocyte Apoptosis in Swine by Activating the LOX-1-Dependent Mitochondrial Pathway and Caspase-8-Dependent Pathway. AB - BACKGROUND: Cardiomyocyte apoptosis by coronary microembolization (CME) contributes to myocardial dysfunction, in which mitochondrial pathway and death receptor pathway are activated. Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) is a membrane protein involved in apoptosis. The study aimed to explore the role of LOX-1 in the activation of these 2 major apoptotic pathways. METHODS: Twenty Bama miniature swine were randomized into 4 groups (n = 5 per group). The groups were Sham, CME, LOX-1 small-interfering RNA (siRNA), and control siRNA. Microspheres were injected into the left anterior descending artery of swine to establish CME model. Twelve hours after operation, cardiac function, serum c-troponin I level, microinfarct, and apoptotic index were examined. The levels of LOX-1, Bcl-2, Bax, cytochrome c as well as cleaved caspase 9, -8, and -3 were detected. RESULTS: Myocardial dysfunction, enhanced serum c-troponin I, microinfarct, and apoptosis were induced following CME. Moreover, CME induced increased expression of LOX-1, Bax, cytochrome c, cleaved caspase 9, -8, and -3 as well as decreased Bcl-2 expression levels. The LOX-1 siRNA reversed these effects by CME except cleaved caspase 8 expression, while the control siRNA had no effect. CONCLUSION: Coronary microembolization induces cardiomyocyte apoptosis via the LOX-1-dependent mitochondrial pathway and caspase 8-dependent pathway. PMID- 26275409 TI - Does prior local corticosteroid injection prejudice the outcome of subsequent carpal tunnel decompression? AB - It has been suggested that treatment of carpal tunnel syndrome by local corticosteroid injection may prejudice the outcome of subsequent surgery. We identified patients who had proceeded directly to carpal tunnel surgery and patients who had initially been treated with one or more injections and then subsequently underwent carpal tunnel surgery on the same hand. Outcomes of surgery were evaluated using pre- and post-operative Boston carpal tunnel syndrome scales and an ordinal scale for overall satisfaction. Multivariate models were created to study the effect of pre-operation injection on the surgical outcome while controlling for demographic and clinical variables. A total of 942 patients were included; 85% of the direct group and 84% of the prior injection group reported themselves either completely cured or much improved after surgery. Post-operative symptom severity and functional status scores showed no significant difference between the direct-to-surgery and prior injection groups. Prior local steroid injection does not prejudice the outcome of surgery. LEVEL OF EVIDENCE: IV. PMID- 26275410 TI - Beyond cigarette smoking: smoke-free home rules and use of alternative tobacco products. AB - BACKGROUND: A smoke-free home rule has been associated with reduced cigarette consumption; however, it is unknown whether a home rule is associated with the use of alternative tobacco products (ATP) such as smokeless tobacco products, regular and water pipes, and cigars. This study examined the association between the smoke-free home rules and ever and current use of ATP. METHOD: Data from the 2010-2011 US Tobacco Use Supplements to the Current Population Survey were analysed using multivariable logistic regressions, including variables related to smoke-free home rules. RESULTS: Overall, 83.9% respondents reported a smoke-free home rule inside their homes; 20.6% of respondents had tried at least one type of ATP, and 3.9% were current users in 2010-2011. Having a smoke-free home rule was associated with lower likelihood of current versus never use of any ATP (adjusted odds ratio (AOR) = 0.80, 95% confidence interval (CI): 0.77-0.83). Among ever users of any ATP, the existence of a smoke-free home rule was associated with lower odds of being a current user (AOR = 0.49, 95% CI: 0.43-0.56). Similar associations were observed for each type of ATP examined (p < 0.05). CONCLUSION: Smoke-free home rules are associated with lower current ATP use among the US population. Future research should examine whether promoting smoke-free home rules could help to reduce ATP use and related diseases. PMID- 26275411 TI - Letter from doctors urging Wellcome Trust to divest from fossil fuels nears 1000 signatories. PMID- 26275412 TI - Does the National Health Insurance Scheme provide financial protection to households in Ghana? AB - BACKGROUND: Excessive healthcare payments can impede access to health services and also disrupt the welfare of households with no financial protection. Health insurance is expected to offer financial protection against health shocks. Ghana began the implementation of its National Health Insurance Scheme (NHIS) in 2004. The NHIS is aimed at removing the financial barrier to healthcare by limiting direct out-of-pocket health expenditures (OOPHE). The study examines the effect of the NHIS on OOPHE and how it protects households against catastrophic health expenditures. METHODS: Data was obtained from a cross-sectional representative household survey involving 2,430 households from three districts across Ghana. All OOPHE associated with treatment seeking for reported illness in the household in the last 4 weeks preceding the survey were analysed and compared between insured and uninsured persons. The incidence and intensity of catastrophic health expenditures (CHE) among households were measured by the catastrophic health payment method. The relative effect of NHIS on the incidence of CHE in the household was estimated by multiple logistic regression analysis. RESULTS: About 36% of households reported at least one illness during the 4 weeks period. Insured patients had significantly lower direct OOPHE for out-patient and in patient care compared to the uninsured. On financial protection, the incidence of CHE was lower among insured households (2.9%) compared to the partially insured (3.7%) and the uninsured (4.0%) at the 40% threshold. The incidence of CHE was however significantly lower among fully insured households (6.0%) which sought healthcare from NHIS accredited health facilities compared to the partially insured (10.1%) and the uninsured households (23.2%). The likelihood of a household incurring CHE was 4.2 times less likely for fully insured and 2.9 times less likely for partially insured households relative to being uninsured. The NHIS has however not completely eliminated OOPHE for the insured and their households. CONCLUSION: The NHIS has significant effect in reducing OOPHE and offers financial protection against CHE for insured individuals and their households though they still made some out-of-pocket payments. Efforts should aim at eliminating OOPHE for the insured if the objective for establishing the NHIS is to be achieved. PMID- 26275413 TI - An Examination of Women Ex-Offenders With Methadone Histories. AB - Criminal (drug and prostitution) charges, employment levels (weekly hours), recent substance use in the past 6 months, and primary sources of income were examined among a sample ( n = 106) of women ex-offenders who had opioid use disorders with and without methadone histories. A general linear model was tested to examine differences in relation to methadone use history. Results from a one way MANCOVA found that those with methadone histories reported significantly higher levels of drug and prostitution charges than those without any methadone history, but no significant differences in terms of weekly hours of employment or recent substance use were observed between groups. Women ex-offenders with methadone histories reported various sources of income beyond employment, and proportionally, more of these women reported prostitution as a primary source of income. Findings suggest that methadone maintenance treatments are not sufficient in meeting the needs of women ex-offenders. PMID- 26275414 TI - Building Bridges in New Jersey. AB - This article describes the experience and outcomes of the National Institute on Drug Abuse-funded Criminal Justice Drug Abuse Treatment Studies 2 Improving Best Practices in Assessment and Case Planning for Offenders protocol in the state of New Jersey. The protocol was designed to test the effectiveness of an Organizational Process Improvement Intervention in improving four assessment and case planning domains for drug-involved offenders in correctional settings transferring to community treatment based agencies. This article describes the protocol and the change team model process through which correctional and community agency staff collaborated to improve assessment and case planning for offenders with substance abuse problems. The primary goal of these collaborative efforts was to link information across stages of the treatment continuum to improve service coordination. Data taken from qualitative interviews with agency participants are used to illustrate the common themes that emerged relating to the intervention process, barriers to implementing developed goals, and facilitative factors that contributed to successes. The findings from the current study provide indication that organizational process improvement strategies can be implemented within a correctional setting to reduce interorganizational barriers and to facilitate improvements in the continuum of care involved in the treatment of offenders with histories of substance abuse. PMID- 26275415 TI - Prevalence and correlates of oral human papillomavirus infection among healthy males and females in Lima, Peru. AB - PURPOSE: The incidence of human papillomavirus (HPV) associated head and neck cancers (HNCs) have been increasing in Peru. However, the burden of oral HPV infection in Peru has not been assessed. The objective of this cross-sectional study was to estimate the prevalence and correlates of oral HPV infection in a population-based sample from males and females from Lima, Peru. METHODS: Between January 2010 and June 2011, a population-based sample of 1099 individuals between the ages of 10 and 85 from a low-income neighbourhood in Lima, Peru was identified through random household sampling. Information on demographic, sexual behaviours, reproductive factors and oral hygiene were collected using interviewer-administered questionnaires. Oral rinse specimens were collected from each participant, and these specimens were genotyped using the Roche Linear Array assay. ORs were used to assess differences in the prevalence of any oral HPV and any high-risk oral HPV infection by demographic factors, sexual practices and oral hygiene among individuals 15+ years of age. RESULTS: The prevalence of any HPV and any high-risk HPV (HR-HPV) was 6.8% and 2.0%, respectively. The three most common types were HPV 55 (3.4%), HPV 6 (1.5%) and HPV 16 (1.1%). Male sex (aOR, 2.21; 95% CI 1.22 to 4.03) was associated with any HPV infection after adjustment. CONCLUSIONS: The prevalence of oral HPV in this study was similar to estimates observed in the USA. Higher prevalence of oral infections in males was consistent with a male predominance of HPV-associated HNCs and may signal a sex specific aetiology in the natural history of infection. PMID- 26275416 TI - Self-perceived risk and prevalent chlamydia infection among adolescents in Norway: a population-based cross-sectional study. AB - OBJECTIVES: Risk judgements are key factors in adolescents' decisions related to sexual health. We examine the associations between self-perceived risk and prevalent chlamydia infection, and sexual behaviours related to risk perception in a general adolescent population in Norway. METHODS: Population-based cross sectional study among 1028 sexually experienced girls and boys, age 15-20 years (85% participation), including web questionnaires and urine samples for Chlamydia trachomatis PCR testing. Participants rated self-perceived risk as: no/low/medium/high/very high. We used binary and ordinal logistic regressions to examine associations with chlamydia prevalence and self-perceived risk, respectively, adjusting for potentially confounding variables. RESULTS: Chlamydia prevalence increased with increasing risk perception. Although girls had twice the chlamydia prevalence of boys (7.3% vs 3.9%), their risk distribution was similar and 65% of both genders rated their risk as no/low with half of infections detected in this group. In multivariable analyses, reporting multiple sexual risk behaviours, non-steady relationship, previous chlamydia testing and treatment, and urogenital symptoms increased self-perceived risk. More boys overestimated their personal risk whereas more girls underestimated it (52% vs 30%, respectively, and 15% vs 31%, p<0.001). The main reasons for perceiving no/low risk were: 'I have a steady partner' and 'I trust my partner will tell me about an infection'. CONCLUSIONS: These sexually experienced adolescents acknowledged their chlamydia infection risk, but wrong beliefs were incorporated in their assessments, and more than half had incorrect risk perception. We suggest that sexually transmitted infection prevention programmes should be directed at closing the gap between perceived and actual risk and focus on how context may bias personal judgement. PMID- 26275417 TI - Clinical and molecular predictors of mortality in neurofibromatosis 2: a UK national analysis of 1192 patients. AB - BACKGROUND: Neurofibromatosis 2 (NF2) is an autosomal-dominant tumour predisposition syndrome characterised by bilateral vestibular schwannomas, considerable morbidity and reduced life expectancy. Although genotype-phenotype correlations are well established in NF2, little is known about effects of mutation type or location within the gene on mortality. Improvements in NF2 diagnosis and management have occurred, but their effect on patient survival is unknown. METHODS: We evaluated clinical and molecular predictors of mortality in 1192 patients (771 with known causal mutations) identified through the UK National NF2 Registry. Kaplan-Meier survival and Cox regression analyses were used to evaluate predictors of mortality, with jackknife adjustment of parameter SEs to account for the strong intrafamilial phenotypic correlations that occur in NF2. RESULTS: The study included 241 deaths during 10 995 patient-years of follow up since diagnosis. Early age at diagnosis and the presence of intracranial meningiomas were associated with increased mortality, and having a mosaic, rather than non-mosaic, NF2 mutation was associated with reduced mortality. Patients with splice-site or missense mutations had lower mortality than patients with truncating mutations (OR 0.459, 95% CI 0.213 to 0.990, and OR 0.196, 95% CI 0.213 to 0.990, respectively). Patients with splice-site mutations in exons 6-15 had lower mortality than patients with splice-site mutations in exons 1-5 (OR 0.333, 95% CI 0.129 to 0.858). The mortality of patients with NF2 diagnosed in more recent decades was lower than that of patients diagnosed earlier. CONCLUSIONS: Continuing advances in molecular diagnosis, imaging and treatment of NF2 associated tumours offer hope for even better survival in the future. PMID- 26275418 TI - IFT81, encoding an IFT-B core protein, as a very rare cause of a ciliopathy phenotype. AB - BACKGROUND: Bidirectional intraflagellar transport (IFT) consists of two major protein complexes, IFT-A and IFT-B. In contrast to the IFT-B complex, all components of IFT-A have recently been linked to human ciliopathies when defective. We therefore hypothesised that mutations in additional IFT-B encoding genes can be found in patients with multisystemic ciliopathies. METHODS: We screened 1628 individuals with reno-ocular ciliopathies by targeted next generation sequencing of ciliary candidate genes, including all IFT-B encoding genes. RESULTS: Consequently, we identified a homozygous mutation in IFT81 affecting an obligatory donor splice site in an individual with nephronophthisis and polydactyly. Further, we detected a loss-of-stop mutation with extension of the deduced protein by 10 amino acids in an individual with neuronal ceroid lipofuscinosis-1. This proband presented with retinal dystrophy and brain lesions including cerebellar atrophy, a phenotype to which the IFT81 variant might contribute. Cultured fibroblasts of this latter affected individual showed a significant decrease in ciliated cell abundance compared with controls and increased expression of the transcription factor GLI2 suggesting deranged sonic hedgehog signalling. CONCLUSIONS: This work describes identification of mutations of IFT81 in individuals with symptoms consistent with the clinical spectrum of ciliopathies. It might represent the rare case of a core IFT-B complex protein found associated with human disease. Our data further suggest that defects in the IFT-B core are an exceedingly rare finding, probably due to its indispensable role for ciliary assembly in development. PMID- 26275419 TI - Genotoxic capacity of Cd/Se semiconductor quantum dots with differing surface chemistries. AB - Quantum dots (QD) have unique electronic and optical properties promoting biotechnological advances. However, our understanding of the toxicological structure-activity relationships remains limited. This study aimed to determine the biological impact of varying nanomaterial surface chemistry by assessing the interaction of QD with either a negative (carboxyl), neutral (hexadecylamine; HDA) or positive (amine) polymer coating with human lymphoblastoid TK6 cells. Following QD physico-chemical characterisation, cellular uptake was quantified by optical and electron microscopy. Cytotoxicity was evaluated and genotoxicity was characterised using the micronucleus assay (gross chromosomal damage) and the HPRT forward mutation assay (point mutagenicity). Cellular damage mechanisms were also explored, focusing on oxidative stress and mitochondrial damage. Cell uptake, cytotoxicity and genotoxicity were found to be dependent on QD surface chemistry. Carboxyl-QD demonstrated the smallest agglomerate size and greatest cellular uptake, which correlated with a dose dependent increase in cytotoxicity and genotoxicity. Amine-QD induced minimal cellular damage, while HDA-QD promoted substantial induction of cell death and genotoxicity. However, HDA-QD were not internalised by the cells and the damage they caused was most likely due to free cadmium release caused by QD dissolution. Oxidative stress and induced mitochondrial reactive oxygen species were only partially associated with cytotoxicity and genotoxicity induced by the QD, hence were not the only mechanisms of importance. Colloidal stability, nanoparticle (NP) surface chemistry, cellular uptake levels and the intrinsic characteristics of the NPs are therefore critical parameters impacting genotoxicity induced by QD. PMID- 26275420 TI - Influence of Ogg1 repair on the genetic stability of ccc2 mutant of Saccharomyces cerevisiae chemically challenged with 4-nitroquinoline-1-oxide (4-NQO). AB - In Saccharomyces cerevisiae, disruption of genes by deletion allowed elucidation of the molecular mechanisms of a series of human diseases, such as in Wilson disease (WD). WD is a disorder of copper metabolism, due to inherited mutations in human copper-transporting ATPase (ATP7B). An orthologous gene is present in S. cerevisiae, CCC2 gene. Copper is required as a cofactor for a number of enzymes. In excess, however, it is toxic, potentially carcinogenic, leading to many pathological conditions via oxidatively generated DNA damage. Deficiency in ATP7B (human) or Ccc2 (yeast) causes accumulation of intracellular copper, favouring the generation of reactive oxygen species. Thus, it becomes important to study the relative importance of proteins involved in the repair of these lesions, such as Ogg1. Herein, we addressed the influence Ogg1 repair in a ccc2 deficient strain of S. cerevisiae. We constructed ccc2-disrupted strains from S. cerevisiae (ogg1ccc2 and ccc2), which were analysed in terms of viability and spontaneous mutator phenotype. We also investigated the impact of 4-nitroquinoline-1-oxide (4 NQO) on nuclear DNA damage and on the stability of mitochondrial DNA. The results indicated a synergistic effect on spontaneous mutagenesis upon OGG1 and CCC2 double inactivation, placing 8-oxoguanine as a strong lesion-candidate at the origin of spontaneous mutations. The ccc2 mutant was more sensitive to cell killing and to mutagenesis upon 4-NQO challenge than the other studied strains. However, Ogg1 repair of exogenous-induced DNA damage revealed to be toxic and mutagenic to ccc2 deficient cells, which can be due to a detrimental action of Ogg1 on DNA lesions induced in ccc2 cells. Altogether, our results point to a critical and ambivalent role of BER mediated by Ogg1 in the maintenance of genomic stability in eukaryotes deficient in CCC2 gene. PMID- 26275421 TI - Cytochrome b5 reductase 2 suppresses tumor formation in nasopharyngeal carcinoma by attenuating angiogenesis. AB - BACKGROUND: Cytochrome b5 reductase 2 (CYB5R2) is a potential tumor suppressor that inhibits cell proliferation and motility in nasopharyngeal carcinoma (NPC). Inactivation of CYB5R2 is associated with lymph node metastasis in NPC. This study aimed to explore the mechanisms contributing to the anti-neoplastic effects of CYB5R2. METHODS: Polymerase chain reaction (PCR) assays were used to analyze the transcription of 84 genes known to be involved in representative cancer pathways in the NPC cell line HONE1. NPC cell lines CNE2 and HONE1 were transiently transfected with CYB5R2, and data was validated by real-time PCR. A chick chorioallantoic membrane (CAM) embryo model was implanted with CYB5R2 expressing CNE2 and HONE1 cells to evaluate the effect of CYB5R2 on angiogenesis. An immunohistochemical assay of the CAM model was used to analyze the protein expression of vascular endothelial growth factor (VEGF). RESULTS: In CYB5R2 transfected NPC cells, PCR assays revealed up-regulated mRNA levels of Fas cell surface death receptor (FAS), FBJ murine osteosarcoma viral oncogene homolog (FOS), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), integrin beta 3 (ITGB3), metastasis suppressor 1 (MTSS1), interferon beta 1 (IFNB1), and cyclin dependent kinase inhibitor 2A (CDKN2A) and down-regulated levels of integrin beta 5 (ITGB5), insulin-like growth factor 1 (IGF1), TEK tyrosine kinase (TEK), transforming growth factor beta receptor 1 (TGFBR1), and VEGF. The angiogenesis in the CAM model implanted with CYB5R2-transfected NPC cells was inhibited. Down regulation of VEGF by CYB5R2 in NPC cells was confirmed by immunohistochemical staining in the CAM model. CONCLUSION: CYB5R2 up-regulates the expression of genes that negatively modulate angiogenesis in NPC cells and down-regulates the expression of VEGF to reduce angiogenesis, thereby suppressing tumor formation. PMID- 26275422 TI - Energy Homeostasis Control in Drosophila Adipokinetic Hormone Mutants. AB - Maintenance of biological functions under negative energy balance depends on mobilization of storage lipids and carbohydrates in animals. In mammals, glucagon and glucocorticoid signaling mobilizes energy reserves, whereas adipokinetic hormones (AKHs) play a homologous role in insects. Numerous studies based on AKH injections and correlative studies in a broad range of insect species established the view that AKH acts as master regulator of energy mobilization during development, reproduction, and stress. In contrast to AKH, the second peptide, which is processed from the Akh encoded prohormone [termed "adipokinetic hormone precursor-related peptide" (APRP)] is functionally orphan. APRP is discussed as ecdysiotropic hormone or as scaffold peptide during AKH prohormone processing. However, as in the case of AKH, final evidence for APRP functions requires genetic mutant analysis. Here we employed CRISPR/Cas9-mediated genome engineering to create AKH and AKH plus APRP-specific mutants in the model insect Drosophila melanogaster. Lack of APRP did not affect any of the tested steroid-dependent processes. Similarly, Drosophila AKH signaling is dispensable for ontogenesis, locomotion, oogenesis, and homeostasis of lipid or carbohydrate storage until up to the end of metamorphosis. During adulthood, however, AKH regulates body fat content and the hemolymph sugar level as well as nutritional and oxidative stress responses. Finally, we provide evidence for a negative autoregulatory loop in Akh gene regulation. PMID- 26275424 TI - Natural Variation in the Flag Leaf Morphology of Rice Due to a Mutation of the NARROW LEAF 1 Gene in Oryza sativa L. AB - We investigated the natural variations in the flag leaf morphology of rice. We conducted a principal component analysis based on nine flag leaf morphology traits using 103 accessions from the National Institute of Agrobiological Sciences Core Collection. The first component explained 39% of total variance, and the variable with highest loading was the width of the flag leaf (WFL). A genome-wide association analysis of 102 diverse Japanese accessions revealed that marker RM6992 on chromosome 4 was highly associated with WFL. In analyses of progenies derived from a cross between Takanari and Akenohoshi, the most significant quantitative trait locus (QTL) for WFL was in a 10.3-kb region containing the NARROW LEAF 1 (NAL1) gene, located 0.4 Mb downstream of RM6992. Analyses of chromosomal segment substitution lines indicated that a mutation (G1509A single-nucleotide mutation, causing an R233H amino acid substitution in NAL1) was present at the QTL. This explained 13 and 20% of total variability in WFL and the distance between small vascular bundles, respectively. The mutation apparently occurred during rice domestication and spread into japonica, tropical japonica, and indica subgroups. Notably, one accession, Phulba, had a NAL1 allele encoding only the N-terminal, or one-fourth, of the wild-type peptide. Given that the Phulba allele and the histidine-type allele showed essentially the same phenotype, the histidine-type allele was regarded as malfunctional. The phenotypes of transgenic plants varied depending on the ratio of histidine-type alleles to arginine-type alleles, raising the possibility that H(233)-type products function differently from and compete with R(233)-type products. PMID- 26275423 TI - Inner Kinetochore Protein Interactions with Regional Centromeres of Fission Yeast. AB - Centromeres of the fission yeast Schizosaccharomyces pombe lack the highly repetitive sequences that make most other "regional" centromeres refractory to analysis. To map fission yeast centromeres, we applied H4S47C-anchored cleavage mapping and native and cross-linked chromatin immunoprecipitation with paired-end sequencing. H3 nucleosomes are nearly absent from the central domain, which is occupied by centromere-specific H3 (cenH3 or CENP-A) nucleosomes with two H4s per particle that are mostly unpositioned and are more widely spaced than nucleosomes elsewhere. Inner kinetochore proteins CENP-A, CENP-C, CENP-T, CENP-I, and Scm3 are highly enriched throughout the central domain except at tRNA genes, with no evidence for preferred kinetochore assembly sites. These proteins are weakly enriched and less stably incorporated in H3-rich heterochromatin. CENP-A nucleosomes protect less DNA from nuclease digestion than H3 nucleosomes, while CENP-T protects a range of fragment sizes. Our results suggest that CENP-T particles occupy linkers between CENP-A nucleosomes and that classical regional centromeres differ from other centromeres by the absence of CENP-A nucleosome positioning. PMID- 26275425 TI - YKL-40 regulated epithelial-mesenchymal transition and migration/invasion enhancement in non-small cell lung cancer. AB - BACKGROUND: YKL-40 is a secreted inflammatory protein that its overexpression has been reported to correlate with poor outcome of various malignant diseases, especially in cancer. However, the function of this protein is still unclear. METHODS: The clinical prognosis of non-small cell lung cancers (NSCLC) patients and their clinical YKL-40 expressions were obtained from the Prognoscan database. The expressions of YKL-40 in patient samples were determined by Western Blotting assay. YKL-40 gene knockdown and overexpression were performed on NSCLC cancer cells (CL1-1 and CL1-5). The cells were investigated for their epithelial mesenchymal transition (EMT) markers gene modulation through Western Blotting and RT-PCR. Further cell metastatic abilities were assessed by transwell migration and invasion assay. RESULT: In this study, YKL-40 was observed to be highly expressed in NSCLC specimens. Furthermore, determined by the PrognoScan database analysis, patients with high expression levels of YKL-40 were found with poor prognosis. In the in vitro study, different characteristics of NSCLC cell lines (CL1-1, H23, H838, CL1-5, and H2009) were used as study models, where YKL-40 expression levels were determined to correlate with the phenotypic characteristics of cancer metastasis. In this study,YKL-40 was demonstrated to regulate EMT marker expressions such as Twist, Snail, Slug, N-cadherin, Vimentin, and E-cadherin. The protein's affects in cancer cell migration and invasion were also observed in YKL-40 overexpression or knock down NSCLC cell lines. CONCLUSION: All of results from this study suggest that YKL-40 is a major factor in NSCLC metastasis. Thus, YKL-40 may serve as therapeutic targets for NSCLC patients in the future. PMID- 26275426 TI - Criteria for social media-based scholarship in health professions education. AB - BACKGROUND: Social media are increasingly used in health professions education. How can innovations and research that incorporate social media applications be adjudicated as scholarship? OBJECTIVE: To define the criteria for social media based scholarship in health professions education. METHOD: In 2014 the International Conference on Residency Education hosted a consensus conference of health professions educators with expertise in social media. An expert working group drafted consensus statements based on a literature review. Draft consensus statements were posted on an open interactive online platform 2 weeks prior to the conference. In-person and virtual (via Twitter) participants modified, added or deleted draft consensus statements in an iterative fashion during a facilitated 2 h session. Final consensus statements were unanimously endorsed. RESULTS: A review of the literature demonstrated no existing criteria for social media-based scholarship. The consensus of 52 health professions educators from 20 organisations in four countries defined four key features of social media-based scholarship. It must (1) be original; (2) advance the field of health professions education by building on theory, research or best practice; (3) be archived and disseminated; and (4) provide the health professions education community with the ability to comment on and provide feedback in a transparent fashion that informs wider discussion. CONCLUSIONS: Not all social media activities meet the standard of education scholarship. This paper clarifies the criteria, championing social media-based scholarship as a legitimate academic activity in health professions education. PMID- 26275427 TI - Learning theory and its application to the use of social media in medical education. AB - BACKGROUND: There is rapidly increasing pressure to employ social media in medical education, but a review of the literature demonstrates that its value and role are uncertain. OBJECTIVE: To determine if medical educators have a conceptual framework that informs their use of social media and whether this framework can be mapped to learning theory. METHODS: Thirty-six participants engaged in an iterative, consensus building process that identified their conceptual framework and determined if it aligned with one or more learning theories. RESULTS: The results show that the use of social media by the participants could be traced to two dominant theories-Connectivism and Constructivism. They also suggest that many medical educators may not be fully informed of these theories. CONCLUSIONS: Medical educators' use of social media can be traced to learning theories, but these theories may not be explicitly utilised in instructional design. It is recommended that formal education (faculty development) around learning theory would further enhance the use of social media in medical education. PMID- 26275428 TI - Quality indicators for blogs and podcasts used in medical education: modified Delphi consensus recommendations by an international cohort of health professions educators. AB - BACKGROUND: Quality assurance concerns about social media platforms used for education have arisen within the medical education community. As more trainees and clinicians use resources such as blogs and podcasts for learning, we aimed to identify quality indicators for these resources. A previous study identified 151 potentially relevant quality indicators for these social media resources. OBJECTIVE: To identify quality markers for blogs and podcasts using an international cohort of health professions educators. METHODS: A self-selected group of 44 health professions educators at the 2014 International Conference on Residency Education participated in a Social Media Summit during which a modified Delphi consensus study was conducted to determine which of the 151 quality indicators met the a priori >=90% inclusion threshold. RESULTS: Thirteen quality indicators classified into the domains of credibility (n=8), content (n=4) and design (n=1) met the inclusion threshold. CONCLUSIONS: The quality indicators that were identified may serve as a foundation for further research on quality indicators of social media-based medical education resources and prompt discussion of their legitimacy as a form of educational scholarship. PMID- 26275429 TI - Efficacy and safety of tofacitinib following inadequate response to conventional synthetic or biological disease-modifying antirheumatic drugs. AB - OBJECTIVES: Biological disease-modifying antirheumatic drugs (bDMARDs) have shown diminished clinical response following an inadequate response (IR) to >=1 previous bDMARD. Here, tofacitinib was compared with placebo in patients with an IR to conventional synthetic DMARDs (csDMARDs; bDMARD-naive) and in patients with an IR to bDMARDs (bDMARD-IR). METHODS: Data were taken from phase II and phase III studies of tofacitinib in patients with rheumatoid arthritis (RA). Patients received tofacitinib 5 or 10 mg twice daily, or placebo, as monotherapy or with background methotrexate or other csDMARDs. Efficacy endpoints and incidence rates of adverse events (AEs) of special interest were assessed. RESULTS: 2812 bDMARD naive and 705 bDMARD-IR patients were analysed. Baseline demographics and disease characteristics were generally similar between treatment groups within subpopulations. Across subpopulations, improvements in efficacy parameters at month 3 were generally significantly greater for both tofacitinib doses versus placebo. Clinical response was numerically greater with bDMARD-naive versus bDMARD-IR patients (overlapping 95% CIs). Rates of safety events of special interest were generally similar between tofacitinib doses and subpopulations; however, patients receiving glucocorticoids had more serious AEs, discontinuations due to AEs, serious infection events and herpes zoster. Numerically greater clinical responses and incidence rates of AEs of special interest were generally reported for tofacitinib 10 mg twice daily versus tofacitinib 5 mg twice daily (overlapping 95% CIs). CONCLUSIONS: Tofacitinib demonstrated efficacy in both bDMARD-naive and bDMARD-IR patients with RA. Clinical response to tofacitinib was generally numerically greater in bDMARD naive than bDMARD-IR patients. The safety profile appeared similar between subpopulations. TRIAL REGISTRATION NUMBERS: (NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385). PMID- 26275431 TI - In the idiopathic inflammatory myopathies, reactive oxygen species are at the crossroad between immune and non-immune cell-mediated mechanisms. PMID- 26275430 TI - MICL controls inflammation in rheumatoid arthritis. AB - BACKGROUND: Myeloid inhibitory C-type lectin-like receptor (MICL, Clec12A) is a C type lectin receptor (CLR) expressed predominantly by myeloid cells. Previous studies have suggested that MICL is involved in controlling inflammation. OBJECTIVE: To determine the role of this CLR in inflammatory pathology using Clec12A(-/-) mice. METHODS: Clec12A(-/-) mice were generated commercially and primarily characterised using the collagen antibody-induced arthritis (CAIA) model. Mechanisms and progress of disease were characterised by clinical scoring, histology, flow cytometry, irradiation bone-marrow chimera generation, administration of blocking antibodies and in vivo imaging. Characterisation of MICL in patients with rheumatoid arthritis (RA) was determined by immunohistochemistry and single nucleotide polymorphism analysis. Anti-MICL antibodies were detected in patient serum by ELISA and dot-blot analysis. RESULTS: MICL-deficient animals did not present with pan-immune dysfunction, but exhibited markedly exacerbated inflammation during CAIA, owing to the inappropriate activation of myeloid cells. Polymorphisms of MICL were not associated with disease in patients with RA, but this CLR was the target of autoantibodies in a subset of patients with RA. In wild-type mice the administration of such antibodies recapitulated the Clec12A(-/-) phenotype. CONCLUSIONS: MICL plays an essential role in regulating inflammation during arthritis and is an autoantigen in a subset of patients with RA. These data suggest an entirely new mechanism underlying RA pathogenesis, whereby the threshold of myeloid cell activation can be modulated by autoantibodies that bind to cell membrane-expressed inhibitory receptors. PMID- 26275432 TI - Whole-genome single nucleotide polymorphism-based linkage analysis in spondyloarthritis multiplex families reveals a new susceptibility locus in 13q13. AB - OBJECTIVE: Spondyloarthritis (SpA) is a chronic inflammatory disorder with high heritability but with complex genetics. Apart from HLA-B27, most of the underlying genetic components remain to be identified. We conducted a whole genome high-density non-parametric linkage analysis to identify new genetic factors of susceptibility to SpA. METHODS: 914 subjects including 462 with SpA from 143 multiplex families were genotyped using Affymetrix 250K microarrays. After quality control, 189 368 single nucleotide polymorphisms (SNPs) were kept for further analyses. Both non-parametric and parametric linkage analyses were performed using Merlin software. Association was tested with Unphased. RESULTS: Non-parametric linkage analysis identified two regions significantly linked to SpA: the major histocompatibility complex (LODmax=24.77) and a new 13q13 locus (LODmax=5.03). Additionally, eight loci achieved suggestive LOD scores, including the previously identified SPA2 locus at 9q33 (LODmax=3.51). Parametric analysis supported a codominant model in 13q13 with a maximum heterogeneity LOD, 'HLOD' score of 3.084 (alpha=0.28). Identification of meiotic recombination events around the 13q13 linkage peak in affected subjects from the 43 best-linked families allowed us to map the disease interval between 38.753 and 40.040 Mb. Family-based association analysis of the SNPs inside this interval in the best linked families identified a SNP near FREM2 (rs1945502) which reached a p value close to statistical significance (corrected p=0.08). CONCLUSION: We report here for the first time a significant linkage between 13q13 and SpA. Identification of susceptibility factor inside this chromosomal region through targeted sequencing in linked families is underway. PMID- 26275433 TI - Neuroimaging's Role in Neuropsychology: Introduction to the Special Issue of Neuropsychology Review on Neuroimaging in Neuropsychology. PMID- 26275434 TI - Effect of different feed ingredients and additives on IPEC-J2 cells challenged with an enterotoxigenic Escherichia coli strain. AB - The intestinal porcine epithelial cell line IPEC-J2 was used as an in vitro model to assess effects of additives on the adhesion and cell toxic effects of a F4 positive (ETEC) and a F4-negative Escherichia coli (DSM 2840) strain. Bacterial adhesion was examined using flow cytometry in IPEC-J2 cells infected with bacteria stained with 5,6-carboxymethyl fluorescein diacetate succinimidyl ester. Measurement of transepithelial electrical resistance (TEER) was performed to characterize the impact on IPEC-J2 monolayer integrity. The feed additives were prepared as aqueous extract and tested in different dilutions and incubation times. The F4-positive ETEC strain had a high adhesion to IPEC-J2 cells and reduced TEER shortly after the in vitro infection. The nonpathogenic E. coli strain DSM 2840 showed only low adhesion capacity and no TEER impairment. Infection with ETEC with added test extracts showed a reduction of bacterial adhesion to IPEC-J2 cells by an autolyzed yeast product (p < 0.05). Bovine colostrum, an additive containing thyme extract and an organic acid mix did not interfere with the ETEC adherence. The TEER decrease of the IPEC-J2 monolayer after ETEC infection was not affected by the added substances. In conclusion, interference with epithelial adhesion might be a protective mechanism of the tested yeast extract, indicating that the cell culture model might be suitable as screening tool to complement in vivo challenge trials with piglets. PMID- 26275435 TI - Mechanism of triphenylmethane Cresol Red degradation by Trichoderma harzianum M06. AB - Cresol Red belongs to the triphenylmethane (TPM) class of dyes which are potentially carcinogenic or mutagenic. However, very few studies on biodegradation of Cresol Red were investigated as compared to other type dyes such as azo and anthraquinone dye. The aim of this work is to evaluate triphenylmethane dye Cresol Red degradation by fungal strain isolated from the decayed wood in Johor Bahru, Malaysia. Detailed taxonomic studies identified the organisms as Trichoderma species and designated as strain Trichoderma harzianum M06. In this study, Cresol Red was decolorized up to 88% within 30 days under agitation condition by Trichoderma harzianum M06. Data analysis revealed that a pH value of 3 yielded a highest degradation rate among pH concentrations (73%), salinity concentrations of 100 g/L (73%), and a volume of 0.1 mL of Tween 80 (79%). Induction in the enzyme activities of manganese peroxidase, lignin peroxidase, laccase, 1,2- and 2,3-dioxygenase indicates their involvement in Cresol Red removal. Various analytical studies such as Thin-Layer Chromatography (TLC), UV-Vis spectrophotometer, and Gas chromatography mass spectrometry (GC-MS) confirmed the biotransformation of Cresol Red by the fungus. Two metabolites were identified in the treated medium: 2,4-dihydroxybenzoic acid (t R 7.3 min and m/z 355) and 2-hydroxybenzoic acid (t R 8.6 min and m/z 267). Based on these products, a probable pathway has been proposed for the degradation of Cresol Red by Trichoderma harzianum M06. PMID- 26275436 TI - Chiba Tendril-Less locus determines tendril organ identity in melon (Cucumis melo L.) and potentially encodes a tendril-specific TCP homolog. AB - Tendrils are filamentous plant organs that coil on contact with an object, thereby providing mechanical support for climbing to reach more sunlight. Plant tendrils are considered to be modified structure of leaves, stems, or inflorescence, but the origin of cucurbit tendrils is still argued because of the complexity in the axillary organ patterning. We carried out morphological and genetic analyses of the Chiba Tendril-Less (ctl) melon (Cucumis melo) mutant, and found strong evidence that the melon tendril is a modified organ derived from a stem-leaf complex of a lateral shoot. Heterozygous (CTL/ctl) plants showed traits intermediate between tendril and shoot, and ontogenies of wild-type tendrils and mutant modified shoots coincided. We identified the CTL locus in a 200-kb region in melon linkage group IX. A single base deletion in a melon TCP transcription factor gene (CmTCP1) was detected in the mutant ctl sequence, and the expression of CmTCP1 was specifically high in wild-type tendrils. Phylogenetic analysis demonstrated the novelty of the CmTCP1 protein and the unique molecular evolution of its orthologs in the Cucurbitaceae. Our results move us closer to answering the long-standing question of which organ was modified to become the cucurbit tendril, and suggest a novel function of the TCP transcription factor in plant development. PMID- 26275437 TI - Characterization of an acromesomelic dysplasia, Grebe type case: novel mutation affecting the recognition motif at the processing site of GDF5. AB - Acromesomelic dysplasia, Grebe type is a very rare skeletal dysplasia characterized by severe dwarfism with marked micromelia and deformation of the upper and lower limbs, with a proximodistal gradient of severity. CDMP1 gene mutations have been associated with Grebe syndrome, Hunter-Thompson syndrome, Du Pan syndrome and brachydactyly type C. The proband is a 4-year-old boy, born of consanguineous Pakistani parents. Radiographic imaging revealed features typical of Grebe syndrome: severe shortening of the forearms with an acromesomelic pattern following a proximodistal gradient, with distal parts more severely affected than medial parts; hypoplastic hands, with the phalangeal zone more affected than the metacarpal zone; and severe hypoplastic tibial/femoral zones in both limbs. After molecular analyses, the p.Arg377Trp variant in a homozygous pattern was identified in the CDMP1 gene in the affected child. In silico and structural analyses predicted the p.Arg377Trp amino acid change to be pathogenic. Of the 34 mutations described in the CDMP1 gene, four different missense mutations have been associated with Grebe syndrome. The CDMP1 gene encodes growth differentiation factor 5 (GDF5), which plays a role in regulation of limb patterning, joint formation and distal bone growth. Homozygous mutations in the mature domain of GDF5 result in severe limb malformations such as the Grebe type or the Hunter-Thompson type of acromesomelic chondrodysplasia. The p.Arg377Trp mutation is located within the recognition motif at the processing site of GDF5 where the sequence RRKRR changes to WRKRR. The genotype-phenotype correlation allowed not only confirmation of the clinical diagnosis but also appropriate genetic counselling to be offered to this family. PMID- 26275438 TI - A 2-year prospective densitometric study on the influence of Fok-I gene polymorphism in young patients with thalassaemia major. AB - This study is to estimate the degree of genetic contribution of Fok-I gene polymorphism of Vitamin D receptor to bone mass in patients with thalassaemia. Results indicate a protective role of the f allele of the Fok-I gene polymorphism when found in homozygosity on bone mineral density of young thalassemic patients. INTRODUCTION: The purpose of this study is to estimate prospectively the degree of genetic contribution of Fok-I gene polymorphism of vitamin D receptor (VDR) to the evolution of bone mass in patients with beta-thalassemia major (b-TH). METHODS: Sixty-four children and young adults (33 males and 31 females) with mean decimal age of 23.20 +/- 5.41 (range 9.25-32.41 years) were recruited in this study. All patients were genotyping for Fok-I gene polymorphism and were assessed with dual energy X-ray absorptiometry (DXA) at baseline and 2 years after. Z scores were calculated based on normal age and sex matched Caucasian population. Metabolites of vitamin D, intact PTH, total calcium, inorganic phosphorous, and alkaline phosphatase were measured at the serum pre-transfusion. RESULTS: A moderate proportion of patients had decreased DXA Z-scores (Z-score <=-2) predominately in total hip (31 %) and secondary in lumbar spine (15.6 %). Patients being homozygous for the f allele had apparently higher BMD Z-scores compared with those carrying the F allele in homo- or heterozygosity, however, with a difference that did not reached significance. Interestingly enough, a significant deterioration in BMD Z-scores measured at femur (FF: P = 0.004 Ff: P < 0.001, ff: P = 0.024) and total hip (FF: P = 0.022, Ff: P = 0.005) was recorded for all type of genotypes, except for ff genotype and with regard to the total hip DXA values. An increased prevalence of serum 25(OH)D3 deficiency (59.4 %) and 25(OH)D3 borderline (12.5 %) was recorded. CONCLUSION: Our study indicates a protective role of the f allele of the Fok-I gene polymorphism when found in homozygosity on bone mineral density of young patients with b-TM. PMID- 26275439 TI - Cost-effectiveness of a fracture liaison service--a real-world evaluation after 6 years of service provision. AB - The cost-effectiveness of a less intensive fracture liaison service is unknown. We evaluated a fracture liaison service that had been educating and referring patients for secondary prevention of osteoporotic fractures for 6 years. Our results suggest that a less intensive fracture liaison service, with moderate effectiveness, can still be worthwhile. INTRODUCTION: Fragility fractures are common among older patients; the risk of re-fracture is high but could be reduced with treatments; different versions of fracture liaison service have emerged to reduce recurrent osteoporotic fractures. But the cost-effectiveness of a less intensive model is unknown. The objective of this study was to assess the cost effectiveness of the Ontario Fracture Clinic Screening program, a fracture liaison service that had been educating and referring fragility fracture patients across Ontario, Canada to receive bone mineral density testing and osteoporosis treatments since 2007. METHODS: We developed a Markov model to assess the cost effectiveness of the program over the patients' remaining lifetime, using rates of bone mineral density testing and osteoporosis treatment and cost of intervention from the program, and supplemented it with the published literature. The analysis took the perspective of a third-party health-care payer. Costs and benefits were discounted at 5 % per year. Sensitivity analyses assessed the effects of different assumptions on the results. RESULTS: The program improved quality-adjusted life-years (QALYs) by 4.3 years and led to increased costs of CAD $83,000 for every 1000 patients screened, at a cost of $19,132 per QALY gained. The enhanced model, the Bone Mineral Density (BMD) Fast Track program that includes ordering bone mineral density testing, was even more cost-effective ($5720 per QALY gained). CONCLUSIONS: The Ontario Fracture Clinic Screening program appears to be a cost-effective way to reduce recurrent osteoporotic fractures. PMID- 26275440 TI - The CXCR1/2 Pathway: Involvement in Diabetes Pathophysiology and Potential Target for T1D Interventions. AB - Although numerous chemokine/chemokine receptor pathways have been described to be implicated in the pathogenesis of type 1 diabetes (T1D), the CXCR1/2 axis has recently been proved to be crucial for leucocyte recruitment involved in insulitis and beta cell damage. Multiple strategies blocking the CXCR1/2 pathway are available such as neutralizing antibodies, small molecules and peptide derived inhibitors. They were firstly and widely used in cancer thanks to their anti-tumorigenic activity and only recently they were tested as a new interventional approach for T1D. As well, CXCR1/2 inhibition has been demonstrated to prevent inflammation- and autoimmunity-mediated damage of the pancreatic islets through inhibiting the migration of CXCR1/2-expressing cells. Among them, neutrophils, macrophages, and, although to a smaller extent, lymphoid cells are the main CXCR1/2-expressing cells. These results supported the active role of the innate immunity in the autoimmune process and opened new interventional approaches for the management of T1D. PMID- 26275441 TI - Pediatric Autologous Islet Transplantation. AB - A total pancreatectomy and islet autotransplant (TPIAT) offers substantial pain relief and improved quality of life for children who are severely affected by chronic or recurrent acute pancreatitis and for whom the usual medical and endoscopic therapies have failed. The pancreas is entirely resected, and the pancreatic islets are isolated from the pancreas and infused back into the patient's liver. Because this is an autologous transplant, no immunosuppression is required. Over several months, the islets engraft in the liver; the patient is then slowly weaned off insulin therapy. Slightly more than 40 % of patients become and remain insulin independent, yet even among patients who remain on insulin, most have some islet function, permitting easier diabetes control. The majority of patients experience pain relief, with significant improvements in health-related quality of life. A TPIAT should be considered for children who are significantly disabled by chronic pancreatitis. PMID- 26275442 TI - Dual Renin-Angiotensin-Aldosterone System Inhibition for the Treatment of Diabetic Kidney Disease: Adverse Effects and Unfulfilled Promise. AB - Diabetic nephropathy (DN) is a major complication of diabetes mellitus (DM) affecting individuals with type 1 or type 2 DM and is the leading cause of chronic kidney disease and end-stage kidney disease (ESKD) in the USA. Estimates of disease burden are projected to increase, with prevalence of nearly one in five adults by 2050. The role of renin-angiotensin-aldosterone system (RAAS) inhibition in delaying the progression of DN utilizing angiotensin-converting enzyme inhibitors or angiotensin receptor blockers has been well established in multiple controlled trials. Given greater reduction of proteinuria with dual RAAS blockade compared to monotherapy alone, the potential benefit of dual therapy on progression of DN has been tested in three large randomized clinical trials. Unfortunately, results from these studies demonstrated lack of benefit of dual blockade on renal or cardiovascular outcomes in patients with diabetes. The overall objectives of this review are to provide both the rationale for dual blockade as potential therapy as well as review the literature of its use in patients with DN. PMID- 26275443 TI - Tissue-Engineering Approaches to Restore Kidney Function. AB - Kidney transplantation for the treatment of chronic kidney disease has established outcome and quality of life. However, its implementation is severely limited by a chronic shortage of donor organs; consequently, most candidates remain on dialysis and on the waiting list while accruing further morbidity and mortality. Furthermore, those patients that do receive kidney transplants are committed to a life-long regimen of immunosuppressive drugs that also carry significant adverse risk profiles. The disciplines of tissue engineering and regenerative medicine have the potential to produce alternative therapies which circumvent the obstacles posed by organ shortage and immunorejection. This review paper describes some of the most promising tissue-engineering solutions currently under investigation for the treatment of acute and chronic kidney diseases. The various stem cell therapies, whole embryo transplantation, and bioengineering with ECM scaffolds are outlined and summarized. PMID- 26275444 TI - Prevalence of Diabetic Retinopathy and Vision Loss in the Beijing Eye Study: the Potential Role of the Cerebrospinal Fluid Pressure. AB - In the Beijing Eye Study, a population-based study carried out in 2001, 2006, and 2011, prevalence of diabetic retinopathy (DR) was 2.9 +/- 0.3 % (95 % confidence interval 2.3, 3.5) per individual in 2011. Correspondingly, only 1.1 % of blindness and 0.8 % of visual impairment were caused by DR in East Asia. As in other populations, prevalence, severity, and 10-year incidence of DR were associated with higher levels of HbA1c, higher blood glucose concentration, longer known duration of diabetes, lower educational level, and higher blood pressure. Interestingly, the presence, severity, and 10-year incidence of DR were additionally correlated with higher estimated cerebrospinal fluid pressure and shorter ocular length. Higher cerebrospinal fluid pressure may lead to higher retinal vein pressure and subsequently higher retinal capillary blood pressure increasing fluid and blood extravasation. Shorter axial length or hyperopia may be associated with higher intraocular concentration of cytokines. Aging of the society, improvements in medical infrastructure, and lifestyle changes may profoundly increase prevalence of, and burden by, DR in China in the future. PMID- 26275445 TI - A Novel Targeted Screening Tool for Hypogammaglobulinemia: Measurement of Serum Immunoglobulin (IgG, IgM, IgA) Levels from Dried Blood Spots (Ig-DBS Assay). AB - PURPOSE: To develop an assay to quantify serum immunoglobulin (IgG, IgM, IgA) levels using dried blood spots (DBS) obtained on collection cards to be used as a tool for targeted screening for hypogammaglobulinemia. METHODS: DBS samples, along with simultaneous serum samples, were collected from 107 healthy individuals (11 months to 57 years of age). After eluting proteins from DBS, IgG, IgM, and IgA were quantified by an enzyme-linked immunosorbent assay (ELISA). The Ig-DBS assay was validated through calibration curve performance, intra- and inter-assay precision, accuracy, specificity, selectivity, and linearity. The ELISA measurements were compared with serum Ig levels obtained using a standard nephelometry assay on serum samples collected simultaneously with the DBS samples and the results of the two assays were correlated. The stability of IgG, IgM, and IgA in the DBS was tested at room temperature, 36 degrees to 38 degrees C, 2 to 8 degrees C, and -25 to -40 degrees C, from 4 to 14 days. RESULTS: The Ig-DBS assay demonstrated precision, accuracy, specificity, selectivity, and linearity. Using the identified correlation coefficients of 0.834 for IgG, 0.789 for IgM, and 0.918 for IgA, the standard nephelometry-based normal reference ranges for all 3 serum Ig isotypes could be used with the Ig-DBS assay in individuals >=16 years of age. The DBS samples were stable for 14 days at room temperature in a closed polyethylene bag. CONCLUSIONS: The Ig-DBS assay is both sensitive and accurate for quantification of serum immunoglobulins. Samples are sufficiently stable at ambient temperature to allow for convenient shipping and analysis at a centralized laboratory. This assay therefore presents a new option for screening patients >=16 years of age for hypogammaglobulinemia in any setting. PMID- 26275446 TI - Protamine-stabilized RNA as an ex vivo stimulant of primary human dendritic cell subsets. AB - Dendritic cells (DCs) are key in connecting innate and adaptive immunity. Their potential in inducing specific immune responses has made them interesting targets for immunotherapeutic approaches. Our research group was the first to exploit the naturally occurring myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in therapeutic vaccination trials against melanoma. To develop primary DC subsets as an optimal vaccine, the identification of a clinically applicable adjuvant activating both subsets is required. Although the expression of pathogen recognition receptors differs distinctly between the DC subsets, both pDCs and mDCs can respond to single-stranded RNA (ssRNA) via Toll-like receptors 7 and 8, respectively. Since ssRNA is easily degraded by RNases, we stabilized anionic RNA by complexing it with the positively charged protein protamine. This leads to the formation of protamine-RNA complexes with varying features depending on ionic content. We subsequently investigated the immunostimulatory effect of complexes that formed various salt concentrations on purified DC subsets. Both mDCs and pDCs upregulated maturation markers and produced pro-inflammatory cytokines in a dose dependent way to the protamine-RNA complexes. This was dependent on endosomal acidification and correlated partly with the uptake of protamine-RNA complexes. Furthermore, both DC subsets induced T cell proliferation and IFN gamma secretion in a beneficial ratio to IL-10. These results indicate that protamine-RNA complexes can be used to stimulate human mDC and pDC ex vivo for use in immunotherapeutic settings. PMID- 26275447 TI - Simultaneous reconstruction of attenuation and activity in cardiac PET can remove CT misalignment artifacts. AB - BACKGROUND: Misalignment between positron emission tomography (PET) and computed tomography (CT) data is known to generate artifactual defects in cardiac PET images due to imprecise attenuation correction (AC). In this work, the use of a maximum likelihood attenuation and activity (MLAA) algorithm is proposed to avoid such artifacts in time-of-flight (TOF) PET. METHODS: MLAA was implemented and tested using a thorax/heart phantom and retrospectively on fourteen (13)N-ammonia PET/CT perfusion studies. Global and local misalignments between PET and CT data were generated by shifting matched CT images or using CT data representative of the end-inspiration phase. PET images were reconstructed with MLAA and a 3D ordered-subsets-expectation-maximization (OSEM)-TOF algorithm. Images obtained with 3D-OSEM-TOF and matched CT were used as references. These images were compared (qualitatively and semi-quantitatively) with those reconstructed with 3D OSEM-TOF and MLAA for which a misaligned CT was used, respectively, for AC and initialization. RESULTS: Phantom experiment proved the capability of MLAA to converge toward the correct emission and attenuation distributions using, as input, only PET emission data, but convergence was very slow. Initializing MLAA with phantom CT images markedly improved convergence speed. In patient studies, when shifted or end-inspiration CT images were used for AC, 3D-OSEM-TOF reconstructions showed artifacts of increasing severity, size, and frequency with increasing mismatch. Such artifacts were absent in the corresponding MLAA images. CONCLUSION: The proposed implementation of the MLAA algorithm is a feasible and robust technique to avoid AC mismatch artifacts in cardiac PET studies provided that a CT of the source is available, even if poorly aligned. PMID- 26275449 TI - Getting it Straight: Avoiding Blunders While Criticizing a Peer's Work. PMID- 26275448 TI - Biomarker candidates for the detection of an infectious etiology of febrile neutropenia. AB - PURPOSE: Infections and subsequent septicemia are major complications in neutropenic patients with hematological malignancies. Here, we identify biomarker candidates for the early detection of an infectious origin, and monitoring of febrile neutropenia (FN). METHODS: Proteome, metabolome, and conventional biomarkers from 20 patients with febrile neutropenia without proven infection (FNPI) were compared to 28 patients with proven infection, including 17 patients with bacteremia. RESULTS: Three peptides (mass to charge ratio 1017.4-1057.3; p values 0.011-0.024), six proteins (mass to charge ratio 6881-17,215; p-values 0.002-0.004), and six phosphatidylcholines (p-values 0.007-0.037) were identified that differed in FNPI patients compared to patients with infection or bacteremia. Seven of these marker candidates discriminated FNPI from infection at fever onset with higher sensitivity and specificity (ROC-AUC 0.688-0.824) than conventional biomarkers i.e., procalcitonin, C-reactive protein, or interleukin-6 (ROC-AUC 0.535-0.672). In a post hoc analysis, monitoring the time course of four lysophosphatidylcholines, threonine, and tryptophan allowed for discrimination of patients with or without resolution of FN (ROC-AUC 0.648-0.919) with higher accuracy compared to conventional markers (ROC-AUC 0.514-0.871). CONCLUSIONS: Twenty-one promising biomarker candidates for the early detection of an infectious origin or for monitoring the course of FN were found which might overcome known shortcomings of conventional markers. PMID- 26275450 TI - Data Resource Profile: The Cardiovascular Disease Lifetime Risk Pooling Project. PMID- 26275451 TI - Authors' Response to: Data sources for measuring the socioeconomic gradient of hypertension in rural populations of low- and middle-income countries. PMID- 26275452 TI - Data sources for measuring the socioeconomic gradient of hypertension in rural populations of low- and middle-income countries. PMID- 26275454 TI - Health & Demographic Surveillance System Profile: The Dikgale Health and Demographic Surveillance System. PMID- 26275453 TI - Effect of fortified complementary food supplementation on child growth in rural Bangladesh: a cluster-randomized trial. AB - BACKGROUND: Growth faltering in the first 2 years of life is high in South Asia where prevalence of stunting is estimated at 40-50%. Although nutrition counselling has shown modest benefits, few intervention trials of food supplementation exist showing improvements in growth and prevention of stunting. METHODS: A cluster-randomized controlled trial was conducted in rural Bangladesh to test the effect of two local, ready-to-use foods (chickpea and rice-lentil based) and a fortified blended food (wheat-soy-blend++, WSB++) compared with Plumpy'doz, all with nutrition counselling vs nutrition counselling alone (control) on outcomes of linear growth (length and length-for-age z-score, LAZ), stunting (LAZ < -2), weight-for-length z-score (WLZ) and wasting (WLZ < -2) in children 6-18 months of age. Children (n = 5536) were enrolled at 6 months of age and, in the food groups, provided with one of the allocated supplements daily for a year. RESULTS: Growth deceleration occurred from 6 to 18 months of age but deceleration in LAZ was lower (by 0.02-0.04/month) in the Plumpy'doz (P = 0.02), rice-lentil (< 0.01), and chickpea (< 0.01) groups relative to control, whereas WLZ decline was lower only in Plumpy'doz and chickpea groups. WSB++ did not impact on these outcomes. The prevalence of stunting was 44% at 18 months in the control group, but lower by 5-6% (P <= 0.01) in those receiving Plumpy'doz and chickpea. Mean length and LAZ at 18 months were higher by 0.27-0.30 cm and 0.07 0.10 (all P < 0.05), respectively, in all four food groups relative to the control. CONCLUSIONS: In rural Bangladesh, small amounts of daily fortified complementary foods, provided for a year in addition to nutrition counselling, modestly increased linear growth and reduced stunting at 18 months of age. PMID- 26275455 TI - Nature-Based Strategies for Improving Urban Health and Safety. AB - Place-based programs are being noticed as key opportunities to prevent disease and promote public health and safety for populations at-large. As one key type of place-based intervention, nature-based and green space strategies can play an especially large role in improving health and safety for dwellers in urban environments such as US legacy cities that lack nature and greenery. In this paper, we describe the current understanding of place-based influences on public health and safety. We focus on nonchemical environmental factors, many of which are related to urban abandonment and blight. We then review findings from studies of nature-based interventions regarding impacts on health, perceptions of safety, and crime. Based on our findings, we suggest that further research in this area will require (1) refined measures of green space, nature, and health and safety for cities, (2) interdisciplinary science and cross-sector policy collaboration, (3) observational studies as well as randomized controlled experiments and natural experiments using appropriate spatial counterfactuals and mixed methods, and (4) return-on-investment calculations of potential economic, social, and health costs and benefits of urban greening initiatives. PMID- 26275457 TI - Malignant transformation and overall survival of morphological subtypes of intraductal papillary mucinous neoplasms of the pancreas: A network meta analysis. AB - BACKGROUND: Emerging evidence suggests the predictive role of morphological subtypes (gastric, intestinal, pancreatobiliary, and oncocytic) of intraductal papillary mucinous neoplasms (IPMNs) in malignant transformation and overall survival. But results of these studies are currently discordant. METHODS: A comprehensive literature search in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) was conducted for eligible studies. Network meta analysis using the random-effect model was carried out to detect differences in incidences of invasive IPMNs and hazard ratios from survival curves among four morphological subtypes. RESULTS: 19 studies were included in the network comparison. The outcomes showed that pancreatobiliary-type (OR for odds ratio=25.87, 95% CI: 12.11-52.10, compared with gastric-type) and oncocytic-type (OR=18.59, 95% CI: 7.18-42.74) IPMNs had the highest risks of progressing to invasive IPMNs, followed by intestinal-type (OR=5.71, 95% CI: 2.85-10.61) and gastric-type IPMNs. With the gastric type as the baseline, pancreatobiliary-type IPMNs were found to have the worst prognosis (HR for hazard ratio=5.05, 95% CrI: 1.33-13.47) while no significant differences were found for the intestinal type (HR=1.90, 95% CrI: 0.59-4.58) and the oncocytic type (HR=3.29, 95% CrI: 0.75 9.71). CONCLUSION: It is suggested that pancreatobiliary-type IPMNs are the most likely to become invasive and are associated with poor prognosis. In contrast, the other three subtypes have similar overall survivals even though the oncocytic and intestinal-type IPMNs are predisposed to be more invasive than gastric-type IPMNs. PMID- 26275456 TI - Results of the Adequacy of glycemiC Control in pAtients with type 2 Diabetes mEllitus treated with Metformin monotherapY at the maximal-tolerated dose (ACCADEMY) study. AB - The treatment objective in diabetes is prevention of the onset or progression of complications. Intensive treatment reduces the risk of complications. The aim of the study was to evaluate glycemic control in patients with type 2 diabetes mellitus treated with metformin monotherapy at the maximal-tolerated dose. This retrospective, multicenter, observational study, enrolled patients >=45-year old receiving metformin as monotherapy for at least 36 months. Data were collected on demographic and disease characteristics, clinical status, lifestyle, comorbidities, and diabetes complications at baseline, 9, 18, and 24 months. Primary study variables were percentage of patients achieving HbA1c <7 % and mean HbA1c reduction after 9 months. Eligible patients (n = 524, mean age 65.9 +/- 7.9 years) had a mean age at diagnosis of 57.5 +/- 7.9 years. A second antidiabetic drug was added in 24 % of patients (126/524); time to treatment escalation was 44.7 +/- 25.1 months. Regarding primary study variables, 61.7 % of patients (322/522) achieved HbA1c of 7.0 % at 9 months, compared to 37.0 % of patients (194/524) at baseline; mean HbA1c was reduced from 7.30 +/- 0.95 to 6.84 +/- 0.86 % after 9 months. The estimated mean time of exposure above 7 % was 19 months, 15 months for patients >=65-year old, and 21 months for younger patients. Regression analysis revealed that patients with longer disease duration, and patients <65 year old responded less well to metformin. A substantial number of patients continued to receive monotherapy instead of intensified therapy and were exposed to hyperglycemia. PMID- 26275458 TI - Targeting disordered proteins with small molecules using entropy. AB - The human proteome includes many disordered proteins. Although these proteins are closely linked with a range of human diseases, no clinically approved drug targets them in their monomeric forms. This situation arises, at least in part, from the current lack of understanding of the mechanisms by which small molecules bind proteins that do not fold into well-defined conformations. To explore possible solutions to this problem, we discuss quite generally how an overall decrease in the free energy associated with intermolecular binding can originate from different combinations of enthalpic and entropic contributions. We then consider more specifically a mechanism of binding by which small molecules can affect the conformational space of a disordered protein by creating an entropic expansion in which more conformations of the protein become populated. PMID- 26275459 TI - A comparison study on polysaccharides from novel hybrids of Amomum villosum and its female parent. AB - The present study is a comparative study on preliminary characterizations and immunostimulatory activities of water-soluble polysaccharides (WSP) from newly hybrid Amomum villosum and its female parent. First, two kinds of WSP were extracted, respectively from the newly hybrid A. villosum called Spring No.1 (WSPH) and its female parent-Longfruit No.2 (WSPP). Then, the differences of preliminary characterizations and immunostimulatory activities in vivo for these two WSP samples were compared. Experimental results showed that WSPH and WSPP had the same monosaccharide composition, and similar ultraviolet and infrared spectra characteristics of polysaccharides, while their immunostimulatory activities, in terms of the weights of spleen and thymus, pinocytic activity and the level of serum hemolysin, showed no significant differences between the groups treated with WSPH and WSPP, respectively. Combined with the findings from other studies in our research group, these results suggested that this novel hybrid could be an acceptable alternative for cultivation of A. villosum. PMID- 26275460 TI - Inhibition of chrysin on xanthine oxidase activity and its inhibition mechanism. AB - Chrysin, a bioactive flavonoid, was investigated for its potential to inhibit the activity of xanthine oxidase (XO), a key enzyme catalyzing xanthine to uric acid and finally causing gout. The kinetic analysis showed that chrysin possessed a strong inhibition on XO ability in a reversible competitive manner with IC50 value of (1.26+/-0.04)*10(-6)molL(-1). The results of fluorescence titrations indicated that chrysin bound to XO with high affinity, and the interaction was predominately driven by hydrogen bonds and van der Waals forces. Analysis of circular dichroism demonstrated that chrysin induced the conformational change of XO with increases in alpha-helix and beta-sheet and reductions in beta-turn and random coil structures. Molecular simulation revealed that chrysin interacted with the amino acid residues Leu648, Phe649, Glu802, Leu873, Ser876, Glu879, Arg880, Phe1009, Thr1010, Val1011 and Phe1013 located within the active cavity of XO. The mechanism of chrysin on XO activity may be the insertion of chrysin into the active site occupying the catalytic center of XO to avoid the entrance of xanthine and causing conformational changes in XO. Furthermore, the interaction assays indicated that chrysin and its structural analog apigenin exhibited an additive effect on inhibition of XO. PMID- 26275461 TI - Hsa-miR-1 suppresses breast cancer development by down-regulating K-ras and long non-coding RNA MALAT1. AB - MicroRNAs exert their functions by mainly regulating coding genes or long non coding RNA expression. In the present study, we reported that hsa-miR-1 was down regulated in breast cancer tissues. Restoration of miR-1 in breast cancer cells inhibited proliferation, motility and increased apoptosis in vitro. MiR-1 functioned as a tumor suppressor by targeting K-RAS and MALAT1. In addition, the effects of up-regulation of miR-1 were similar to that of silencing K-RAS and MALAT1 in breast cancer cells. In vivo study indicated that restoration of miR-1 inhibited tumor growth and metastasis. Patients with low miR-1 expression had poorer overall survival time than those with high miR-1 expression. Our findings emphasized the potential role of miR-1 as tumor suppressive miRNA in breast cancer. PMID- 26275462 TI - beta-lactoglobulin mutation Ala86Gln improves its ligand binding and reduces its immunoreactivity. AB - beta-Lactoglobulin (beta-LG) is a member of lipocalin superfamily of transporters for small hydrophobic molecules. beta-LG is also one of the major allergens in milk. Despite a lot of researches on decreasing of cow's milk allergenicity, the effects of the mutation of beta-LG on its recognition by IgE from cow's milk allergy (CMA) patients have not been investigated. We described here the expression in the yeast Pichia pastoris of a mutant beta-LG, in which Alanine 86 was changed into Glutamine (Ala86Gln; a mutation on one of the major epitopes of the protein). The purity and native like folded structure of the recombinant Ala86Gln have been demonstrated using circular dichroism, HPLC, SDS-PAGE and mass spectrometry. The effect of the mutation on the binding of IgE from CMA patients to mutant protein was evaluated by ELISA methods and the results showed that the mutation of Ala-86 was associated with weaker binding of IgE from CMA patients to Ala86Gln mutant protein. Subsequently, the binding of various ligands such as retinol, palmitic acid, resveratrol and serotonin, with native, recombinant wild type and Ala86Gln mutant beta-LGs were investigated by fluorescence spectroscopy and an improvement on the binding affinity of the mutated protein to various ligands was observed. PMID- 26275463 TI - Radically new cellulose nanocomposite hydrogels: Temperature and pH responsive characters. AB - Innovation produced for synthesis of radically new stimuli-responsive hydrogels were described. The innovation is based on inclusion of cellulose nanowhiskers (CNW)-polyacrylamide (PAAm) copolymer in poly N-isopropyl acrylamide (PNIPAm) semi interpenetrating network (IPN) hydrogel. After being prepared as per free radical polymerization of AAm onto CNW, the as prepared copolymer was incorporated in a polymerization system, which comprises NIPAm monomer, bismethylene acrylamide (BMA) crosslinker, K2S2O8 initiator and TEMED accelerator, to yield CNW-PAAm-PNIPAm nanocomposite hydrogels. The latter address pH-responsive hydrogel as well as temperature-responsive. Hydrogels exhibit the highest equilibrium swelling ratio (ESR) in acidic medium (pH 4). Meanwhile they perform good swelling behavior and hydrophilicity at a temperature of 32 degrees C. These hydrogels carry the characteristic features of CNW-PAAm copolymer as conducted from FTIR and TGA. The hydrogels are homogenous and well-proportioned network structure with highly connected irregular pores with a large size ranging from 30 to 100nm as concluded from SEM. PMID- 26275464 TI - Oropharyngeal perinatal colonization by human papillomavirus. AB - INTRODUCTION AND OBJECTIVE: Human papillomavirus (HPV) infection is the most common human sexually transmitted disease. It is clinically relevant because this condition is necessary for the development of epithelial cervical cancer, and it is also a factor closely associated with the occurrence of diverse tumours and various benign and malignant lesions of the head and neck area. The infective mechanism in most of these cases is associated with sexual intercourse, but there is recent scientific evidence suggesting that HPV infection may also be acquired by other routes of infection not necessarily linked to sexual contact. One of them is vertical transmission from mother to child, either during pregnancy or at the time of delivery. The aim of our research was to study maternal-foetal HPV transmission during childbirth in detail, establishing the rate of oropharyngeal neonatal HPV in vaginal deliveries. METHOD: The presence and type of HPV viral DNA at the time of delivery in samples of maternal cervical secretions, amniotic fluid, venous cord blood samples and neonatal oropharynx in pregnant women (and their babies) were determined. RESULTS: The rate of oropharyngeal neonatal HPV colonization in vaginal deliveries was 58.24%. CONCLUSIONS: The maternal and neonatal HPV colonization mechanism is essentially, but not exclusively, transvaginal. PMID- 26275465 TI - Vocal cord paralysis following epidural anaesthesia for caesarean. PMID- 26275466 TI - Berberine reduce allergic inflammation in a house dust mite allergic rhinitis mouse model. AB - BACKGROUND: Berberine (Ber), used widely as an antibacterial, antifungal, and anti-inflammatory drug, has long been used as a gastrointestinal remedy in Chinese traditional medicine. Recent reports have suggested that Ber suppresses Th17 responses that was mediated by direct actions on T cells and thymic stromal lymphopoietin production in primary mast cells. It has been suggested that Ber may be useful in treating allergic response. The purpose of this study was to assess the effects of Ber treatment on allergic inflammation in an allergic rhinitis mouse model and to examine the underlying mechanism(s). METHODS: BALB/c mice were divided into control, Derf with no treated (Derf), Ber treated, and Ber with anti-C25 monoclonal antibody treated (Ber + anti-CD25) groups. All mice, with the exception of the control group, were sensitized with an intraperitoneal i.p. injection of Dermatophagoides farinae (Derf). Mice in the Ber and Ber + anti CD25 group were treated intranasally with 10 #181;g/mL. Then, 1 week after sensitization, all mice were challenged intranasally with 20 #181;g Derf for 5 consecutive days. Mice in the anti-CD25 group were treated intraperitoneally with 250 #181;g anti-CD25 monoclonal antibody 1 day before the first intra-nasal challenge with Derf. Allergic symptom scores, eosinophil counts, and serum Derf specific IgE levels were measured. T-bet, GATA-3, interferon-g (IFN-gamma), interleukin (IL)-10, IL-13, and Foxp3 expression was examined by real-time polymerase chain reaction and Western blotting. CD4+ CD25+ Foxp3+ T cells were assessed by flow cytometry. RESULTS: Symptom scores, serum Derf-specific IgE levels, GATA-3 mRNA levels, T-bet mRNA levels, and tissue eosinophil counts were decreased in the Ber versus the Derf group. In the Ber + anti-CD25 group, serum IL-10 levels were decreased versus the control, Derf, and Ber groups. In the Ber + anti-CD25 mAb groups, Foxp3 mRNA levels were decreased versus the control group. In the Ber group, Foxp3 mRNA levels were increased versus the control group. In the Ber group, the percentage of CD4+ CD25+ Foxp3+ T cells was increased versus the Derf group. The percentage of CD4+ CD25+ Foxp3+ T cells was increased in the Ber versus the Derf groups. CONCLUSIONS: In our study, Ber reduced allergic inflammation significantly. Moreover, our findings suggest that the mechanism of action of Ber may be via CD4+ CD25+ Foxp3+ Treg cells, possibly through not only by increasing their numbers but also altering their function. PMID- 26275468 TI - Whole genomic constellation of the first human G8 rotavirus strain detected in Japan. AB - Human G8 Rotavirus A (RVA) strains are commonly detected in Africa but are rarely detected in Japan and elsewhere in the world. In this study, the whole genome sequence of the first human G8 RVA strain designated AU109 isolated in a child with acute gastroenteritis in 1994 was determined in order to understand how the strain was generated including the host species origin of its genes. The genotype constellation of AU109 was G8-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Phylogenetic analyses of the 11 genome segments revealed that its VP7 and VP1 genes were closely related to those of a Hungarian human G8P[14] RVA strain and these genes shared the most recent common ancestors in 1988 and 1982, respectively. AU109 possessed an NSP2 gene closely related to those of Chinese sheep and goat RVA strains. The remaining eight genome segments were closely related to Japanese human G2P[4] strains which circulated around 1985-1990. Bayesian evolutionary analyses revealed that the NSP2 gene of AU109 and those of the Chinese sheep and goat RVA strains diverged from a common ancestor around 1937. In conclusion, AU109 was generated through genetic reassortment event where Japanese DS-1-like G2P[4] strains circulating around 1985-1990 obtained the VP7, VP1 and NSP2 genes from unknown ruminant G8 RVA strains. These observations highlight the need for comprehensive examination of the whole genomes of RVA strains of less explored host species. PMID- 26275467 TI - [Neck bronchogenic cyst. Case report and review of the literature]. AB - BACKGROUND: Bronchogenic cyst is a malformation of the ventral portion of the intestine, which is limited by bronchial epithelium and produces alterations in the development of the tracheobronchial tree. They may be single or multiple, and are usually confined to one lung or to the mediastinum, rarely to the neck, which is a subcutaneous tissue. OBJECTIVE: The case of a 9 year old girl is reported, who presented with a clinical picture characterized by a slow-growing, asymptomatic tumour on the left side of the neck of 4 years onset. Chest X-ray, neck ultrasound and computed tomography of the neck and chest ruled out any other injury. A complete resection was performed, and the histopathological study confirmed the diagnosis of bronchogenic cyst. CONCLUSION: The symptomatology of a bronchogenic cyst is due to the compression of the vascular, digestive or air structures, as well as its size, infection and location. The treatment of choice is a surgical resection, even when asymptomatic. PMID- 26275469 TI - Increasing pro-survival factors within whole brain tissue of Sprague Dawley rats via intracerebral administration of modified valproic acid. AB - Neural tissue exposure to valproic acid (VPA) increases several pro-survival phospho-proteins that can be used as biomarkers for indicating a beneficial drug response (pAkt(Ser473), pGSK3beta(Ser9), pErk1/2(Thr202/Tyr204)). Unfortunately, targeting VPA to neural tissue is a problem due to severe asymmetrical distribution, wherein the drug tends to remain in peripheral blood rather than localizing within the brain. Intracerebral delivery of an amide-linked VPA-PEG conjugate could address these issues by enhancing retention and promoting cerebro global increases in pro-survival phospho-proteins. It is necessary to assay for the retained bioactivity of a PEGylated valproic acid molecule, along with locating an intracranial cannula placement that optimizes the increase of a known downstream biomarker for chronic VPA exposure. Here we show an acute injection of VPA-PEG conjugate within brain tissue increased virtually all of the assayed phospho-proteins, including well-known pro-survival factors. In contrast, an acute injection of VPA expectedly decreased signaling throughout the hour. Needle penetration into whole brain tissue is the intentional cause of trauma in this procedure. The trauma to brain tissue was observed to overcome known phospho protein increases for unmodified VPA in the injected solution, while VPA-PEG conjugate appeared to induce significant increases in pro-survival phospho proteins, despite the procedural trauma. PMID- 26275470 TI - Novel ruthenium(II) cyclopentadienyl thiosemicarbazone compounds with antiproliferative activity on pathogenic trypanosomatid parasites. AB - Searching for new prospective antitrypanosomal agents, three novel Ru(II) cyclopentadienyl compounds, [Ru(eta(5)-C5H5)(PPh3)L], with HL=bioactive 5 nitrofuryl containing thiosemicarbazones were synthesized and characterized in the solid state and in solution. The compounds were evaluated in vitro on the blood circulating trypomastigote form of Trypanosoma cruzi (Dm28c strain), the infective form of Trypanosoma brucei brucei (strain 427) and on J774 murine macrophages and human-derived EA.hy926 endothelial cells. The compounds were active against both parasites with IC50 values in the micromolar or submicromolar range. Interestingly, they are much more active on T. cruzi than previously developed Ru(II) classical and organometallic compounds with the same bioactive ligands. The new compounds showed moderate to very good selectivity towards the parasites in respect to mammalian cells. The global results point at [RuCp(PPh3)L2] (L2=N-methyl derivative of 5-nitrofuryl containing thiosemicarbazone and Cp=cyclopentadienyl) as the most promising compound for further developments (IC50T. cruzi=0.41MUM; IC50T. brucei brucei=3.5MUM). Moreover, this compound shows excellent selectivity towards T. cruzi (SI>49) and good selectivity towards T. brucei brucei (SI>6). In order to get insight into the mechanism of antiparasitic action, the intracellular free radical production capacity of the new compounds was assessed by ESR. DMPO (5,5-dimethyl-1-pirroline N-oxide) spin adducts related to the bioreduction of the complexes and to redox cycling processes were characterized. In addition, DNA competitive binding studies with ethidium bromide by fluorescence measurements showed that the compounds interact with this biomolecule. PMID- 26275471 TI - Assessment of Choroidal Topographic Changes by Swept-Source Optical Coherence Tomography After Intravitreal Ranibizumab for Exudative Age-Related Macular Degeneration. AB - PURPOSE: To investigate choroidal topographic changes by swept-source optical coherence tomography (Swept-OCT) in patients undergoing intravitreal injections of anti-vascular endothelial growth factor (VEGF) for exudative age-related macular degeneration (AMD). DESIGN: Prospective interventional study. METHODS: Consecutive patients with unilateral treatment-naive exudative AMD were entered into the study over 6 months. Changes in choroidal thickness after intravitreal ranibizumab injections, overall in the macula and in neovascular and non neovascular areas, from baseline to month 3 (loading phase) and month 6 (pro re nata phase), were investigated by means of Swept-OCT maps. RESULTS: Forty-one eyes of 41 patients (mean age: 79.4 +/- 7.3 years) were analyzed. Choroidal thickness at study entry was significantly thicker in the study eyes as compared to fellow eyes (P < .05). Analysis of sectorial choroidal thickness over time in study eyes revealed a significant reduction in both neovascular and non neovascular areas from baseline to month 3 and month 6 (P < .0001 for all). Central choroidal thickness revealed significant variation between treated and fellow eyes from baseline to month 3 (P = .017) and month 6 (P = .045). The visual gain was significantly higher (P = .02) in patients with a larger choroidal thickness reduction (>=29 MUm, n = 11) vs the others (n = 30). CONCLUSIONS: The thinning of the macular choroid (affected or not by choroidal neovascularization), along with the significantly thicker choroid in exudative AMD eyes before treatment initiation compared to fellow eyes, allows the hypothesis that anti-VEGF treatment may favorably influence the choroidal exudation by reducing choroidal vascular hyperpermeability. PMID- 26275473 TI - Prognostic Value of Ocular Trauma Scores in Patients With Combined Open Globe Injuries and Facial Fractures. AB - PURPOSE: To assess the prognostic value of the Ocular Trauma Score in patients with combined open globe injuries and facial fractures. DESIGN: Retrospective cohort study. METHODS: A comprehensive chart review was conducted on 25 patients (28 eyes) identified from the Elmhurst City Hospital Trauma Registry between January 1, 2000 and June 30, 2012. Elmhurst City Hospital is a level 1 trauma center located in Elmhurst, New York, USA. RESULTS: Average age was 52 (range 18 88) and patients were predominantly male (84%). The majority of patients had an Ocular Trauma Score of 1 (87.5%), and of these patients, 76% and 14% had final visual acuities of no light perception (NLP) and light perception/hand motion (LP/HM), respectively. These corresponded to 74% and 15% predicted by the original Ocular Trauma Score guidelines (100% sensitive and 100% specific). Ocular Trauma Score of 1 was associated with zone 3 eye wound location (P = .02). Independent of Ocular Trauma Score, initial visual acuity and frontal bone fractures were predictive of NLP (P = .006 and P = .047). Nonblindness was associated with nasal bone fractures (P = .047). CONCLUSION: This study validates the use of the Ocular Trauma Score in patients with combined facial fracture and open globe injury. The presence of facial fractures does not appear to influence visual prognosis for open globe injuries with an Ocular Trauma Score of 1. In the absence of data to calculate a full Ocular Trauma Score, initial visual acuity was the strongest predictor of final visual outcome. PMID- 26275472 TI - Impact of Free Glasses and a Teacher Incentive on Children's Use of Eyeglasses: A Cluster-Randomized Controlled Trial. AB - PURPOSE: To study the effect of free glasses combined with teacher incentives on in-school glasses wear among Chinese urban migrant children. DESIGN: Cluster randomized controlled trial. METHODS: Children with visual acuity (VA) <=6/12 in either eye owing to refractive error in 94 randomly chosen primary schools underwent randomization by school to receive free glasses, education on their use, and a teacher incentive (Intervention), or glasses prescriptions only (Control). Intervention group teachers received a tablet computer if >=80% of children given glasses wore them during unannounced visits 6 weeks and 6 months (main outcome) after intervention. RESULTS: Among 4376 children, 728 (16.7%, mean age 10.9 years, 51.0% boys) met enrollment criteria and were randomly allocated, 358 (49.2%, 47 schools) to Intervention and 370 (50.8%, 47 schools) to Control. Among these, 693 children (95.2%) completed the study and underwent analysis. Spectacle wear was significantly higher at 6 months among Intervention children (Observed [main outcome]: 68.3% vs 23.9%, adjusted odds ratio [OR] = 11.5, 95% confidence interval [CI] 5.91-22.5, P < .001; Self-reported: 90.6% vs 32.1%, OR = 43.7, 95% CI = 21.7-88.5, P < .001). Other predictors of observed wear at 6 months included baseline spectacle wear (P < .001), uncorrected VA <6/18 (P = .01), and parental spectacle wear (P = .02). The 6-month observed wear rate was only 41% among similar-aged children provided free glasses in our previous trial without teacher incentives. CONCLUSIONS: Free spectacles and teacher incentives maintain classroom wear in the large majority of children needing glasses over a school year. Low wear among Control children demonstrates the need for interventions. PMID- 26275474 TI - Convergence Insufficiency Symptom Survey Scores for Reading Versus Other Near Visual Activities in School-Age Children. AB - PURPOSE: To measure the difference in Convergence Insufficiency Symptom Survey scores for reading vs favorite near visual activities. DESIGN: Comparative validity analysis of diagnostic tools. METHODS: At a single clinical private practice, 100 children aged 9-18 with normal binocular vision were recruited to receive either the original survey emphasizing reading or a modified survey replacing "reading" with their favorite near activity. Average survey scores and subscores for questions emphasizing fatigue, discomfort, impaired vision, and cognitive performance were compared using t tests, while responses to individual questions were compared using Mann-Whitney U tests. RESULTS: The average reading survey score was significantly greater than the favorite near activity survey score (14.1 +/- 11.5 vs 6.7 +/- 5.8, P = .0001). The largest difference resulted from questions emphasizing cognitive performance (subscore 5.8 +/- 4.3 vs 2.0 +/- 2.1, P = .0000002), although significant differences were also found for fatigue (5.4 +/- 3.8 vs 3.0 +/- 2.7, P = .0003), discomfort (3.9 +/- 4.6 vs 1.8 +/- 2.2, P = .004), and impaired vision (3.2 +/- 3.9 vs 1.8 +/- 2.2, P = .02). Significant differences were found for 7 survey questions, with higher symptom scores for the reading survey in every case. Using survey scores >=16 to diagnose convergence insufficiency, significantly more children taking the reading survey would have been diagnosed with convergence insufficiency than children taking the favorite near activity survey (19 of 50 [38%] vs 5 of 50 [10%], P = .001). CONCLUSIONS: By emphasizing reading, the Convergence Insufficiency Symptom Survey score significantly overestimates near visual symptoms in children with normal binocular vision compared with symptoms caused by preferred near activities that require similar amplitudes of accommodation and convergence. PMID- 26275475 TI - Distance from accessible specialist care and other determinants of advanced or unknown stage at diagnosis of people with non-small cell lung cancer: A data linkage study. AB - BACKGROUND: Access to specialist services may influence stage at cancer diagnosis and whether cancer is ever adequately staged. We investigated associations of distance to the nearest accessible specialist hospital (NASH) with likelihood of advanced or unknown stage cancer at diagnosis in Australian non-small cell lung cancer (NSCLC) patients. METHODS: Cancer registry records for 22,260 consecutively diagnosed NSCLC patients, 11,147 with linked records of hospital admissions, were analysed. Distances from patients' homes to the NASH were measured using geographical coordinates. Multinomial logistic regression analysis examined associations of distance from the NASH, type of hospital of treatment and other characteristics of NSCLC patients with advanced and unknown cancer stage. RESULTS: Odds of advanced stage and unknown stage NSCLC were higher in people who lived 40-99 km, OR 1.18 (95%CI 1.07-1.31) advanced stage and 1.18 (1.04-1.33) unknown stage, and 100 km+ from the NASH, OR 1.17 (1.08-1.27) advanced stage and OR 1.38 (1.25-1.52) unknown stage (reference group patients living 0-39 km from the NASH). For hospitalised patients likelihoods of advanced stage and unknown stage NSCLC were also significantly higher in patients treated in general hospitals than in those treated in specialist hospitals. When both distance and hospital type were considered, patients who lived 100 km+ from the NASH had low odds of unknown stage cancer if admitted to a specialist hospital, OR 0.63 (95%CI 0.47-0.85), but a high odds of unknown stage if admitted to a general hospital, OR 2.13 (1.78-2.54). These associations were independent of age, sex, socioeconomic status, comorbidity, period and method of diagnosis, and histopathological subtype. CONCLUSIONS: People living remotely from accessible specialist services are at greatest risk of advanced stage or unknown stage disease if diagnosed with NSCLC. This risk is greater again if the patient is treated in a general hospital. Barriers to referral for specialist care require investigation. PMID- 26275476 TI - Adjuvant therapy for EGFR mutant and ALK positive NSCLC: Current data and future prospects. AB - Tyrosine kinase inhibitors (TKIs) against targetable mutations such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are highly effective in treating advanced stage lung cancers harboring such mutations. Questions remain, however, about whether these agents can improve cure rates for early stage lung cancers in the adjuvant setting. Here, we examine the current data and ongoing trials addressing this issue. PMID- 26275477 TI - Improved quantification of protein in vaccines containing aluminum hydroxide by simple modification of the Lowry method. AB - Aluminum (Al) components in vaccines are known to act as adsorbents that interfere with accurate protein quantification by the Lowry method. Therefore, certain modifications based on the characteristics and compositions of the vaccine are required for determination of protein contents. We investigated the effects of an additional centrifugal separation and found that protein contents were overestimated by up to 238% without centrifugation through a collaborative study performed with hepatitis B vaccines containing Al. However, addition of a centrifugation step yielded protein concentrations that were similar to the actual values, with small coefficients of variation (CVs). Proficiency testing performed in 11 laboratories showed that four laboratories did not have satisfactory results for vaccines containing aluminum hydroxide, although all laboratories were proficient in protein analysis when samples did not contain aluminum hydroxide. Incomplete resuspension of aluminum hydroxide solution with alkaline copper solution was the major cause of insufficient proficiency in these laboratories. PMID- 26275478 TI - Management and outcome of Bacille Calmette-Guerin vaccine adverse reactions. AB - BACKGROUND: Bacille Calmette-Guerin (BCG) vaccine is one of the most widely used vaccines globally. Management of local BCG complications (injection site reactions and suppurative or non-suppurative lymphadenitis) varies between clinicians, and the optimal approach remains uncertain. AIM: To determine the clinical features, management and outcome of BCG complications at two large acute hospitals in London, United Kingdom. METHODS: All children presenting with complications of BCG vaccination between January 2008 and December 2013 were included in this observational study. Medical and electronic laboratory records were reviewed to determine clinical features, treatment and outcome. RESULTS: Sixty children presented with adverse reactions. Two-thirds (65%) presented with BCG lymphadenitis, one-third (30%) presented with injection site complications and two children (3%) presented with both injection site reaction and lymphadenitis; only one child (2%) had disseminated BCG disease. The majority (88%) of children with injection site reactions were managed conservatively; overall, 95% showed complete resolution within 6 months. Among children with lymphadenitis, 46% were managed conservatively, whilst 54% had anti-tuberculous therapy and/or a procedure (aspiration mostly, or surgery); complete resolution was seen in 59% of cases. CONCLUSIONS: Injection site reactions and non suppurative lymphadenitis were generally managed conservatively, with good outcomes. There was more variation in management and outcome of suppurative lymphadenitis and the optimal approach remains uncertain. PMID- 26275479 TI - Rubella specific cell-mediated and humoral immunity following vaccination in college students with low antibody titers. AB - OBJECTIVE: This study measured cell-mediated immunity (CMI) and antibodies to clarify the basis of rubella reinfection after vaccination. METHODS: In a pool of 65 college students, 39 who exhibited hemagglutination-inhibition (HI) antibody titers against rubella of <= 1:16 were vaccinated with a rubella vaccine. The CMI was assessed with interferon-gamma release assay. RESULTS: There was low correlation (r = 0.24) between the antibody titers and interferon-gamma levels at pre-vaccination status. Preexisting interferon-gamma levels were low in some subjects with low HI antibody titers of 1:8 and 1:16. Fifty-seven percent (4/7) of the subjects who were antibody-negative with past history of rubella vaccination at entry onto the study exhibited CMI. And 57% (4/7) of the subjects remained antibody-negative following a second vaccination, despite exhibiting CMI. HI antibody titers increased significantly after vaccination, whereas post vaccination interferon-gamma levels did not exhibit significant increases. When subjects were divided (based on their past history of vaccination and antibody values) into natural infection and vaccination groups, HI antibody titers (mean +/- SD) increased to 1:2(4.4 +/- 1.4) from 1: 2(3.2 +/- 0.4) (p = 0.065) in the natural infection group and to 1:2(4.4 +/- 1.0) from 1:2(3.0 +/- 0.8) (p < 0.00001) in the vaccination group following vaccination. The same classification revealed that interferon-gamma values did not increase significantly in either group following vaccination, but the interferon-gamma values at pre- and post vaccination in the natural infection group were significantly higher than those at pre- and post-vaccination in the vaccination group (p < 0.05 and p < 0.05, respectively). CONCLUSION: Pre-vaccination interferon-gamma levels in each HI antibody titer group were similar. And there were some subjects with antibody positive exhibited CMI-negative. These data may explain why rubella reinfection can occur in vaccinated seropositive individuals. PMID- 26275481 TI - Validation of alternative potency assays for influenza vaccines requires clinical studies. AB - Readers of this Special Issue of Vaccine are likely unified by a desire to enhance vaccine efficacy and improve vaccine manufacturing efficiency. For influenza vaccines, challenges to achieving those goals are many, and range from improved surveillance to less cumbersome production platforms and more reliable performance verification. Specifically, demand is growing for an alternative vaccine potency assay. Assuming that a replacement potency assay is found to be promising, one question will be: how will it be judged to be accurate? It is generally agreed that any potential replacement for SRID will have to exhibit good correlation with SRID and yield a value within +/- 20% of the SRID determined potency. In my opinion, SRID itself has enough limitations that judging alternatives relative to that particular standard will not ensure that the industry as a whole transitions to an improved method. In fact, it could blind us to an assay that may ultimately provide a better predictive measure of vaccine efficacy (or immunogenicity). There is only one way to verify that measured potency is correlated with, and predictive of, measured immunogenicity - test the relationship in clinical studies. PMID- 26275480 TI - Immunosuppressive drugs impairs antibody response of the polysaccharide and conjugated pneumococcal vaccines in patients with Crohn's disease. AB - BACKGROUND: Patients with Crohn's disease (CD) have a higher risk of infectious diseases including pneumococcal infections, and the risk increases with immunotherapy. The primary endpoint of this study was to investigate the specific antibody response to two pneumococcal vaccines in CD patients with and without immunosuppressive treatment four weeks post vaccination. METHODS: In a randomized trial of the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 13 valent pneumococcal conjugated vaccine (PCV13), a group of CD patients treated with immunosuppressive drugs (IS) alone or in combination with TNF-alpha antagonists were compared to a group of CD patients not treated with any of these drugs (untreated). Specific pneumococcal antibody concentrations were measured against 12 serotypes common to the two vaccines before and 4 week after vaccination. RESULTS: PCV13 induced a significantly higher antibody response for one serotype (23F) in IS treated patients and for two serotypes (9V and 23F) in untreated patients compared to CD patients vaccinated with PPV23. Untreated PPV23 recipients had higher responses for serotypes 9V and 18C compared to IS+TNF-alpha treated PPV23 recipients. Comparison between treatment groups showed that immunosuppressive treatment impaired the antibody response to both vaccines and that TNF-a treatment further conveyed additional impairment of the response. CONCLUSION: PCV13 induces higher antibody response for some serotypes compared to PPV23. In addition, CD patients treated with immunosuppressive drugs alone or in combination with TNF-alpha antagonists had an impaired antibody response to both PPV23 and PCV13 compared to patients not receiving any of these treatments. The study has been registered in the European Clinical Trials Database (EudraCT, record no 2012-002867-86) and ClinicalTrials.gov (record no. NCT01947010). PMID- 26275482 TI - PACAP as a neuroprotective factor in ischemic neuronal injuries. AB - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 27- or 38-amino acid neuropeptide, which belongs to the vasoactive intestinal polypeptide/glucagon/secretin family. PACAP and its three receptor subtypes are expressed in neural tissues, with PACAP known to exert pleiotropic effects on the nervous system. This review provides an overview of current knowledge regarding the neuroprotective effects, mechanisms of action, and therapeutic potential of PACAP in response to ischemic brain injuries. PMID- 26275483 TI - Texture evolution and mechanical anisotropy of biomedical hot-rolled Co-Cr-Mo alloy. AB - Crystallographic textures and their effect on the mechanical anisotropy of a hot rolled biomedical Co-Cr-Mo alloy were investigated. The hot-rolled Co-28Cr-6Mo 0.13N (mass%) alloy examined here exhibited a monotonic strength increment following hot-rolling reduction, eventually reaching a 0.2% proof stress of 1400 MPa while maintaining acceptable ductility (>10%). The dominant hot-rolling texture was a brass-type component, which is characterized by the alloy's peculiarly low stacking fault energy (SFE) even at hot rolling temperatures, although the minor peaks of the near copper component were also identified. However, because of the onset of dynamic recrystallization (DRX) during the hot rolling process, the texture intensity was relatively weak even after 90% hot rolling, although the grain refinement originating from the DRX was not significant (the "less active DRX" condition increased the strain accumulation during the process, resulting in high-strength samples). The weakened texture development resulted in negligible in-plane anisotropy for the hot-rolled specimen strength, when the specimens were tensile strained in the rolling direction (RD) and transverse direction (TD). The elongation-to-failure, however, exhibited a difference with respect to the tensile loading axis. It is suggested that the ductility anisotropy is closely related to a strain-induced gamma (fcc) > epsilon (hcp) martensitic transformation during tensile loading, resulting in a difference in the proportion of quasi-cleavage fracture surfaces. The obtained results will be helpful in the development of high-strength Co-Cr-Mo alloy plates and sheets, and have implications regarding plastic deformation and texture evolution during the hot rolling of non-conventional metallic materials with low SFE at elevated temperatures, where planar dislocation slips of Shockley partial dislocations and thermally activated process interplay. PMID- 26275484 TI - Effect of Zr, Nb and Ti addition on injection molded 316L stainless steel for bio applications: Mechanical, electrochemical and biocompatibility properties. AB - The research investigated the effect of Zr, Nb and Ti additions on mechanical, electrochemical properties and biocompatibility of injection molded 316L stainless steel. Addition of elemental powder is promoted to get high performance of sintered 316L stainless steels. The amount of additive powder plays a role in determining the sintered microstructure and all properties. In this study, 316L stainless steel powders used with the elemental Zr, Nb and Ti powders. A feedstock containing 62.5 wt% powders loading was molded at different injection molded temperature. The binders were completely removed from molded components by solvent and thermal debinding at different temperatures. The debinded samples were sintered at 1350 degrees C for 60 min. Mechanical, electrochemical property and biocompatibility of the sintered samples were performed mechanical, electrochemical, SBF immersion tests and cell culture experiments. Results of study showed that sintered 316L and 316L with additives samples exhibited high corrosion properties and biocompatibility in a physiological environment. PMID- 26275485 TI - FEM modeling of the reinforcement mechanism of Hydroxyapatite in PLLA scaffolds produced by supercritical drying, for Tissue Engineering applications. AB - Scaffolds have been produced by supercritical CO2 drying of Poly-L-Lactid Acid (PLLA) gels loaded with micrometric fructose particles used as porogens. These structures show a microporous architecture generated by the voids left in the solid material by porogen leaching, while they maintain the nanostructure of the gel, consisting of a network of nanofilaments. These scaffolds have also been loaded with Hydroxyapatite (HA) nanoparticles, from 10 to 50% w/w with respect to the polymer, to improve the mechanical properties of the PLLA structure. Based on miscroscopic and mechanical considerations, we propose a parametric Finite Element Method (FEM) model of PLLA-HA composites that describes the microporous structure as a close-packing of equal spheres and the nanoscale structure as a space frame of isotropic curved fibers. The effect of HA on the mechanical properties of the scaffolds has been modeled on the basis of SEM images and by taking into consideration the formation of concentric cylinders of HA nanoparticles around PLLA nanofibers. Modeling analysis confirms that mechanical properties of these scaffolds depend on nanofibrous network connections and that bending is the major factor causing deformation of the network. The FEM model also takes into account the formation of HA multi-layer coating on some areas in the nanofiber network and its increase in thickness with HA percentage. The Young modulus tends to a plateau for HA percentages larger than 30% w/w and when the coverage of the nanofibers produced by HA nanoparticles reaches a loaded surface index of 0.14 in the FEM model. PMID- 26275486 TI - An atomic finite element model for biodegradable polymers. Part 2. A model for change in Young's modulus due to polymer chain scission. AB - Atomic simulations were undertaken to analyse the effect of polymer chain scission on amorphous poly(lactide) during degradation. Many experimental studies have analysed mechanical properties degradation but relatively few computation studies have been conducted. Such studies are valuable for supporting the design of bioresorbable medical devices. Hence in this paper, an Effective Cavity Theory for the degradation of Young's modulus was developed. Atomic simulations indicated that a volume of reduced-stiffness polymer may exist around chain scissions. In the Effective Cavity Theory, each chain scission is considered to instantiate an effective cavity. Finite Element Analysis simulations were conducted to model the effect of the cavities on Young's modulus. Since polymer crystallinity affects mechanical properties, the effect of increases in crystallinity during degradation on Young's modulus is also considered. To demonstrate the ability of the Effective Cavity Theory, it was fitted to several sets of experimental data for Young's modulus in the literature. PMID- 26275487 TI - Investigation of the mechanical behavior of kangaroo humeral head cartilage tissue by a porohyperelastic model based on the strain-rate-dependent permeability. AB - Solid-interstitial fluid interaction, which depends on tissue permeability, is significant to the strain-rate-dependent mechanical behavior of humeral head (shoulder) cartilage. Due to anatomical and biomechanical similarities to that of the human shoulder, kangaroos present a suitable animal model. Therefore, indentation experiments were conducted on kangaroo shoulder cartilage tissues from low (10(-4)/s) to moderately high (10(-2)/s) strain-rates. A porohyperelastic model was developed based on the experimental characterization; and a permeability function that takes into account the effect of strain-rate on permeability (strain-rate-dependent permeability) was introduced into the model to investigate the effect of rate-dependent fluid flow on tissue response. The prediction of the model with the strain-rate-dependent permeability was compared with those of the models using constant permeability and strain-dependent permeability. Compared to the model with constant permeability, the models with strain-dependent and strain-rate-dependent permeability were able to better capture the experimental variation at all strain-rates (p < 0.05). Significant differences were not identified between models with strain-dependent and strain rate-dependent permeability at strain-rate of 5 * 10(-3)/s (p = 0.179). However, at strain-rate of 10(-2)/s, the model with strain-rate-dependent permeability was significantly better at capturing the experimental results (p < 0.005). The findings thus revealed the significance of rate-dependent fluid flow on tissue behavior at large strain-rates, which provides insights into the mechanical deformation mechanisms of cartilage tissues. PMID- 26275488 TI - Patient-specific simulation of the intrastromal ring segment implantation in corneas with keratoconus. AB - PURPOSE: The purpose of this study was the simulation of the implantation of intrastromal corneal-ring segments for patients with keratoconus. The aim of the study was the prediction of the corneal curvature recovery after this intervention. METHODS: Seven patients with keratoconus diagnosed and treated by implantation of intrastromal corneal-ring segments were enrolled in the study. The 3D geometry of the cornea of each patient was obtained from its specific topography and a hyperelastic model was assumed to characterize its mechanical behavior. To simulate the intervention, the intrastromal corneal-ring segments were modeled and placed at the same location at which they were placed in the surgery. The finite element method was then used to obtain a simulation of the deformation of the cornea after the ring segment insertion. Finally, the predicted curvature was compared with the real curvature after the intervention. RESULTS: The simulation of the ring segment insertion was validated comparing the curvature change with the data after the surgery. Results showed a flattening of the cornea which was in consonance with the real improvement of the corneal curvature. The mean difference obtained was of 0.74 mm using properties of healthy corneas. CONCLUSIONS: For the first time, a patient-specific model of the cornea has been used to predict the outcomes of the surgery after the intrastromal corneal-ring segments implantation in real patients. PMID- 26275489 TI - Dynamic modeling of breast tissue with application of model reference adaptive system identification technique based on clinical robot-assisted palpation. AB - Accurate identification of breast tissue's dynamic behavior in physical examination is critical to successful diagnosis and treatment. In this study a model reference adaptive system identification (MRAS) algorithm is utilized to estimate the dynamic behavior of breast tissue from mechanical stress-strain datasets. A robot-assisted device (Robo-Tac-BMI) is going to mimic physical palpation on a 45 year old woman having a benign mass in the left breast. Stress strain datasets will be collected over 14 regions of both breasts in a specific period of time. Then, a 2nd order linear model is adapted to the experimental datasets. It was confirmed that a unique dynamic model with maximum error about 0.89% is descriptive of the breast tissue behavior meanwhile mass detection may be achieved by 56.1% difference from the normal tissue. PMID- 26275490 TI - Mechanical characterization and modelling of the temperature-dependent impact behaviour of a biocompatible poly(L-lactide)/poly(epsilon-caprolactone) polymer blend. AB - Poly(epsilon-caprolactone) (PCL) is a ductile, bioabsorbable polymer that has been employed as a blend partner for poly(L-lactic acid) (PLLA). An improvement of the material strength and impact resistance of PLLA/PCL polymer blends compared to pure PLLA has been shown previously. To use numerical simulations in the design process of new components composed of the PLLA/PCL blend, a constitutive model for the material has to be established. In this work, a constitutive model for a PLLA/PCL polymer blend is established from the results of compressive tests at high and low strain rates at three different temperatures, including the body temperature. Finite element simulations of the split Hopkinson pressure bar test using the established constitutive model are carried out under the same condition as the experiments. During the experiments, the changes in the diameter and thickness of the specimens are captured by a high speed video camera. The accuracy of the numerical model is tested by comparing the simulation results, such as the stress, strain, thickness and diameter histories of the specimens, with those measured in the experiments. The numerical model is also validated against an impact test of non-homogenous strains and strain rates. The results of this study provide a validated numerical model for a PLLA/PCL polymer blend at strain rates of up to 1800 s(-1) in the temperature range between 22 degrees C and 50 degrees C. PMID- 26275491 TI - Effect of thermal treatment on the bio-corrosion and mechanical properties of ultrafine-grained ZK60 magnesium alloy. AB - The combination of solid solution heat treatments and severe plastic deformation by high-ratio differential speed rolling (HRDSR) resulted in the formation of an ultrafine-grained microstructure with high thermal stability in a Mg-5Zn-0.5Zr (ZK60) alloy. When the precipitate particle distribution was uniform in the matrix, the internal stresses and dislocation density could be effectively removed without significant grain growth during the annealing treatment (after HRDSR), leading to enhancement of corrosion resistance. When the particle distribution was non-uniform, rapid grain growth occurred in local areas where the particle density was low during annealing, leading to development of a bimodal grain size distribution. The bimodal grain size distribution accelerated corrosion by forming a galvanic corrosion couple between the fine-grained and coarse-grained regions. The HRDSR-processed ZK60 alloy with high thermal stability exhibited high corrosion resistance, high strength and high ductility, and excellent superplasticity, which allow the fabrication of biodegradable magnesium devices with complicated designs that have a high mechanical integrity throughout the service life in the human body. PMID- 26275492 TI - Might excess body weight be beneficial for the community-dwelling older people? PMID- 26275493 TI - Low incidence of complications using polyglactin 910 (Vicryl) mesh in breast reconstruction: A systematic review. AB - BACKGROUND: Mastectomy and breast reconstruction are essential parts of the treatment of breast cancer. Acellular dermal matrices (ADMs) have been used for the reconstruction of the lower pole due to many advantages; however, its cost is seen as a major drawback in this era of concern for the allocation of health-care funds. Recently, polyglactin 910 (Vicryl; Ethicon, Somerville, NJ, USA) mesh has been published as an alternative. We assessed the published literature, in particular investigating for studies that compare Vicryl mesh with ADM. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) methodology. Searched databases included Medline/PubMed, Cochrane Reviews, Embase, Web of Science, ClinicalTrials, and SCOPUS. Search criteria were as follows: (1) reporting of clinical data using Vicryl mesh in breast reconstruction, (2) reporting of original data, and (3) outcome of interest reported. RESULTS: We retrieved 290 de-duplicated articles. After title and abstract screening, we dismissed 258 articles, and thus full text was reviewed for 32 articles; only three retrospective articles met inclusion criteria. The total population included 112 patients and 156 breasts. The reported incidence of complications was as follows: infection 2.6% (confidence interval (CI): 0.7-6.6%), reconstruction failure 3.2% (CI: 1.0-7%), and seroma 1.3% (CI: 0.2-4.6%). A seven- to 12-fold cost difference was reported. Follow-up length ranged from 1.2 to 3.6 years. No studies directly compared Vicryl mesh with ADM. CONCLUSIONS: Although the evidence is limited, polyglactin 910 (Vicryl) mesh for immediate breast reconstruction appears to be a potentially safe, effective, and less expensive alternative to ADM. Prospective studies are needed to further compare mesh with ADM. PMID- 26275494 TI - Isomerization of aspartyl residues in crystallins and its influence upon cataract. AB - BACKGROUND: Age-related cataracts, which probably form due to insolubilization of lens proteins, can lead to loss of vision. Although the exact reason is unknown, lens protein aggregation may be triggered by increases in PTMs such as D-beta-, L beta- and D-alpha-Asp isomers. These isomers have been observed in aged lens; however, there have been few quantitative and site-specific studies owing to the lack of a quick and precise method for distinguishing between D- and L-Asp in a peptide or protein. SCOPE OF REVIEW: We describe a new method for detecting peptides containing Asp isomers at individual sites in any protein by using an LC MS/MS system combined with commercial enzymes that specifically react with different isomers. We also summarize current data on the effect of Asp isomerization on lens crystallins. MAJOR CONCLUSIONS: The new technique enabled the analysis of isomers of Asp residues in lens proteins precisely and quickly. An extensive proportion of Asp isomerization was observed at all Asp sites of crystallins in the insoluble fraction of aged lens. In addition, d-amino acid substitutions in crystallin-mimic peptides showed altered structural formation and function. These results indicate that isomerization of Asp residues affects the stability, structure and inter-subunit interaction of lens crystallins, which will induce crystallin aggregation and insolubilization, disrupt the associated functions, and ultimately contribute to the onset of senile cataract formation. GENERAL SIGNIFICANCE: The mechanism underlying the onset of age-related diseases may involve isomerization, whereby D-amino acids are incorporated in the L-amino acid world of life. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease. PMID- 26275496 TI - [Evaluation of the knowledge of patients about the management of treatment with anti-vitamin K drugs in the Service of Cardiology of Ouagadougou]. AB - INTRODUCTION: Vitamin K antagonists (VKA), the most widely prescribed oral anticoagulant therapy, represent a major public health problem by the adverse events related to their use. The aim of this study was to clarify the level of knowledge that patients have about the management of their oral anticoagulant treatment. PATIENTS AND METHODS: This was a descriptive cross-sectional study performed at Yalgado Ouedraogo university Hospital, over a period of three months starting from March 1st to May 31st 2012. A questionnaire was given to patients receiving VKA treatment for at least a month. RESULTS: Seventy patients were enrolled in the study of which 30 men. The median age was 49+/-16 years. Heart disease and venous thromboembolic disease justifying the introduction of VKA treatment were found respectively in 58.6 and 41.4% of the cases. The name of the VKA and the exact reason for the treatment were known respectively in 91.4 and 61.7% of the case. More than half of patients (68.6%) knew that the VKA makes blood more fluid. Forty-six patients (65.7%) cited INR as biological monitoring of treatment but only 28 patients (40%) were aware of INR target values. The majority of patients did not know the risks in case of overdose (72.8%) and underdosing (71.4%). Self-medication by non-steroidal anti-inflammatory drugs was reported by 18 patients (25.7%). Cabbage (74.3%) and lettuce (62.9%) were the main foods reported to be consumed moderately. CONCLUSION: The knowledge of patients on the management of VKA is fragmentary and remains insufficient to ensure the effectiveness of the treatment. The creation of a therapeutic education program is then necessary. PMID- 26275495 TI - Prooxidant and antioxidant properties of salicylaldehyde isonicotinoyl hydrazone iron chelators in HepG2 cells. AB - BACKGROUND: Salicylaldehyde isonicotinoyl hydrazone (SIH) is an iron chelator of the aroylhydrazone class that displays antioxidant or prooxidant effects in different mammalian cell lines. Because the liver is the major site of iron storage, elucidating the effect of SIH on hepatic oxidative metabolism is critical for designing effective hepatic antioxidant therapies. METHODS: Hepatocyte-like HepG2 cells were exposed to SIH or to analogs showing greater stability, such as N'-[1-(2-Hydroxyphenyl)ethyliden]isonicotinoyl hydrazide (HAPI), or devoid of iron chelating properties, such as benzaldehyde isonicotinoyl hydrazone (BIH), and toxicity, oxidative stress and antioxidant (glutathione) metabolism were evaluated. RESULTS: Autoxidation of Fe(2+)in vitro increased in the presence of SIH or HAPI (but not BIH), an effect partially blocked by Fe(2+) chelation. Incubation of HepG2 cells with SIH or HAPI (but not BIH) was non-toxic and increased reactive oxygen species (ROS) levels, activated the transcription factor Nrf2, induced the catalytic subunit of gamma-glutamate cysteine ligase (Gclc), and increased glutathione concentration. Fe(2+) chelation decreased ROS and inhibited Nrf2 activation, and Nrf2 knock-down inhibited the induction of Gclc in the presence of HAPI. Inhibition of gamma-glutamate cysteine ligase enzymatic activity inhibited the increase in glutathione caused by HAPI, and increased oxidative stress. CONCLUSIONS: SIH iron chelators display both prooxidant (increasing the autoxidation rate of Fe(2+)) and antioxidant (activating Nrf2 signaling) effects. GENERAL SIGNIFICANCE: Activation by SIH iron chelators of a hormetic antioxidant response contributes to their antioxidant properties and modulates the anti- and pro-oxidant balance. PMID- 26275497 TI - Calcium signaling and cell proliferation. AB - Cell proliferation is orchestrated through diverse proteins related to calcium (Ca(2+)) signaling inside the cell. Cellular Ca(2+) influx that occurs first by various mechanisms at the plasma membrane, is then followed by absorption of Ca(2+) ions by mitochondria and endoplasmic reticulum, and, finally, there is a connection of calcium stores to the nucleus. Experimental evidence indicates that the fluctuation of Ca(2+) from the endoplasmic reticulum provides a pivotal and physiological role for cell proliferation. Ca(2+) depletion in the endoplasmatic reticulum triggers Ca(2+) influx across the plasma membrane in an phenomenon called store-operated calcium entries (SOCEs). SOCE is activated through a complex interplay between a Ca(2+) sensor, denominated STIM, localized in the endoplasmic reticulum and a Ca(2+) channel at the cell membrane, denominated Orai. The interplay between STIM and Orai proteins with cell membrane receptors and their role in cell proliferation is discussed in this review. PMID- 26275498 TI - Protein phosphatase 1 is a key player in nuclear events. AB - Reversible protein phosphorylation at serine (Ser), threonine (Thr) and tyrosine (Tyr) residues is among the major regulatory mechanism in eukaryotic cells. The eukaryotic genome encodes many protein kinases and protein phosphatases. However, the localization, activity and specificity towards phosphatase substrates are dictated by a large array of phosphatase binding and regulatory subunits. For protein phosphatase 1 (PP1) more than 200 binding subunits have been described. The various PP1 isoforms and the binding subunits can be located throughout the cell, including in the nucleus. It follows that several nuclear specific PP1 binding proteins (PIPs) have been described and these will be discussed. Among them are PNUTS (phosphatase 1 nuclear targeting subunit), NIPP1 (nuclear inhibitor of PP1) and CREB (cAMP-responsive element-binding protein), which have all been associated with transcription. In fact PP1 can associate with transcription factors fulfilling an important regulatory function, in this respect it can bind to Hox11, human factor C1 (HCF1) and myocyte enhancer factor 2 (MEF2). PP1 also regulates cell cycle progression and centrosome maturation and splitting, again by binding to specific regulatory proteins. Moreover, PP1 together with other protein phosphatases control the entry into mitosis by regulating the activity of mitotic kinases. Thus, PP1, its binding proteins and/or the phosphorylation states of both, directly control a vast array of cell nucleus associated functions, many of which are starting to be unraveled. PMID- 26275499 TI - Determination of spatially dependent diffusion parameters in bovine bone using Kalman filter. AB - Although many studies have been made for homogenous constant diffusion, bone is an inhomogeneous material. It has been suggested that bone porosity decreases from the inner boundaries to the outer boundaries of the long bones. The diffusivity of substances in the bone matrix is believed to increase as the bone porosity increases. In this study, an experimental set up is used where bovine bone samples, saturated with potassium chloride (KCl), were put into distilled water and the conductivity of the water was followed. Chloride ions in the bone samples escaped out in the water through diffusion and the increase of the conductivity was measured. A one-dimensional, spatially dependent mathematical model describing the diffusion process is used. The diffusion parameters in the model are determined using a Kalman filter technique. The parameters for spatially dependent at endosteal and periosteal surfaces are found to be (12.8 +/ 4.7) * 10(-11) and (5 +/- 3.5) * 10(-11)m(2)/s respectively. The mathematical model function using the obtained diffusion parameters fits very well with the experimental data with mean square error varies from 0.06 * 10(-6) to 0.183 * 10( 6) (MUS/m)(2). PMID- 26275500 TI - Induction of ovulation in anestrus ewes using a dopamine receptor antagonist. AB - Estradiol decreases the pulse frequency of LH during the nonbreeding season through dopaminergic neurons that results in anestrus in the ewe. Long-term administration of sulpiride, a dopamine antagonist, induced ovulation in seasonally anestrus mares. Accordingly, we tested whether sulpiride would induce ovulatory estrus in seasonally anestrus Malpura ewes. A total of 12 Malpura ewes were divided into sulpiride (at 0.6 mg/kg b.i.d.) or control groups. Anestrus was defined on the basis of the absence of heat signs for 2 months through twice-a day heat detection during the nonbreeding season (October-November) and progesterone level of less than 1 ng/mL. Rates of estrus induction, ovulation, multiple ovulations, and lambing in the sulpiride-treated ewes were 83.3%, 100%, 16.6%, and 66.7%, respectively. The mean interval from treatment to estrus was 5.25 +/- 1.49 days. Progesterone levels were elevated after ovulation significantly on Days 5 and 7 after estrus as compared to Day 0 after sulpiride treatment (P < 0.05). In contrast, none of the control group ewes showed either estrus or ovulation. There was a significant association between sulpiride treatment and estrus induction rate as well as ovulation rate (P < 0.05). It is concluded that the result provides proof of concept that the dopamine antagonist can induce ovulation in seasonally anestrus ewes. PMID- 26275501 TI - Genetics of Hearing Loss--Nonsyndromic. AB - Eighty percent of nonsyndromic hearing losses are caused by autosomal-recessive (AR) inheritance, while most of the other 20% are caused by autosomal-dominant (AD) inheritance. Although AR nonsyndromic SNHL is most commonly caused by GJB2 and SLC26A4, there is no single gene that accounts for any significant proportion of AD SNHL. High-throughput sequencing techniques, also called next-generation sequencing (NGS) or massively parallel sequencing (MPS), may allow for routine definitive diagnosis of all possible genetic causes for hearing loss in the not too-distant future. PMID- 26275502 TI - A highly active recyclable gold-graphene nanocomposite material for oxidative esterification and Suzuki cross-coupling reactions in green pathway. AB - A graphene based composite with gold nanoparticles has been synthesized via a simple chemical route and the structure and compositions of nanocomposite has been characterized. The catalyst was found to be remarkably stable and active for the oxidative esterification of alcohols under present reaction conditions using molecular oxygen as green oxidant and Suzuki cross-coupling reactions between aryl halides and phenylboronic acids using environmentally friendly water as solvent. The versatility of both the protocols was demonstrated by taking a number of substrates. This protocol offers several advantages like high yields, clean reactions, recyclability of the catalyst, reaction in water and use of green oxidant. This study suggests graphene, as an economical substitute for carbon nanotubes, could act as a prominent support in heterogeneous catalysis. PMID- 26275503 TI - Lignopolymers as viscosity-reducing additives in magnesium oxide suspensions. AB - Lignopolymers are a new class of polymer additives with the capability to be used as dispersants in cementitious pastes. Made with kraft lignin cores and grafted polymer side-chains, the custom-synthesized lignopolymers were examined in terms of the molecular architecture for viscosity reducing potential in inert model suspensions. Lignin-poly(acrylic acid) (LPAA) and lignin-polyacrylamide (LPAm) have been found to vary the rheology of magnesium oxide (MgO) suspensions based on differences in chain architecture and particle-polymer interactions. A commercial comb-polymer polycarboxylate ester was compared to LPAA and LPAm at 2.7 mg/mL, a typical dosage for cement admixtures, as well as 0.25mg/mL. It was found that LPAm was a more effective viscosity reducer than both LPAA and the commercial additive at low concentrations, which was attributed to greater adsorption on the MgO particle surface and increased steric dispersion from PAm side-chain extension. The influence of chain adsorption and grafted side-chain molecular weight on rheology was also tested. PMID- 26275504 TI - Hollow polymer nanoparticles with S-nitrosothiols as scaffolds for nitric oxide release. AB - This work reported the design, preparation and characterization of functional hollow polymer nanoparticles with S-nitrosothiol (SNO) as scaffolds for nitric oxide (NO) release in PBS buffer and bovine serum. The thiolated hollow polymer nanoparticles were prepared by distillation precipitation polymerization of ethyleneglycol dimethacrylate (EGDMA) and 2-hydroxyethyl methacrylate (HEMA) in presence of 3-(methacryloxy)propyltrimethoxysilane (MPS)-modified silica as seeds and the selective removal of silica core in hydrofluoric acid (HF) aqueous solution together with the subsequent surface esterification of hydroxyl groups with acryloyl chloride to introduce high density of vinyl groups and further Michael addition of carbon-carbon double bonds with hydrosulfide (HS(-)) anions. S-Nitrosothiol (SNO) functionalized hollow polymer nanoparticles were prepared via nitrosation of the surface thiol groups with acidified nitrite. The releasing characters of SNO-functionalized hollow polymer nanoparticles as NO scaffolds with capacity of 1.55 MUmol/mg were investigated in different media, including PBS buffer exposure to trace copper cations and in real bovine serum. PMID- 26275505 TI - Integration of adsorption and direct bio-reduction of perchlorate on surface of cotton stalk based resin. AB - In this work, perchlorate was first adsorbed by the cotton stalk based resin (CS resin) and then the laden perchlorate was directly reduced by mixed perchlorate reduction bacteria (PRB) on surface of CS-resin. The characteristics of cotton stalk, clean CS-resin, perchlorate-laden CS-resin and bio-regenerated CS-resin were evaluated by XPS, FT-IR, SEM, zeta potential measurements. All characteristics showed clearly that (i) adsorption mechanism of perchlorate onto CS-resin was based on electrostatic attraction; (ii) biological destruction of laden perchlorate was effective for bio-regenerating the saturated CS-resin. The experimental adsorption capacities (Qexp) of perchlorate by CS-resin achieved at equilibrium condition was about 138.9 mg/g. Reduction rate of laden perchlorate on surface of CS-resin were about 2.12, 1.67, 0.032 and 0.009 mg/g(CS-resin)/d for initial redox potentials poised at -193, -70, +169, and +363 mV, respectively. This indicated that the rapid reduction of laden perchlorate may occur only when conditions were present to cause a low Eh. PMID- 26275506 TI - Synthesis of Ti-Ta alloys with dual structure by incomplete diffusion between elemental powders. AB - In this work, powder metallurgical (PM) Ti-Ta alloys were sintered using blended elemental powders. A dual structure, consisting of Ti-rich and Ta-rich zones, was formed due to the insufficient diffusion between Ti and Ta powders. The microstructure, mechanical properties and in vitro biological properties of the alloys were studied. Results indicated that the alloys have inhomogenous microstructures and compositions, but the grain structures were continuous from the Ti-rich zone to the Ta-rich zone. The Ta-rich zone exhibited a much finer grain size than the Ti-rich zone. The alloys had a high relative density in the range of 95-98%, with the porosity increasing with the content of Ta due to the increased difficulty in sintering and the formation of Kirkendall pores. The alloys had a good combination of low elastic modulus and high tensile strength. The strength of alloys was almost doubled compared to that of the ingot metallurgy alloys with the same compositions. The low elastic modulus was due to the residual pores and the alloying effect of Ta, while the high tensile strength resulted from the strengthening effects of solid solution, fine grain size and alpha phase. The alloys had a high biocompatibility due to the addition of Ta, and were suitable for the attachment of cells due to the surface porosity. It was also indicated that PM Ti-(20-30)Ta alloys are promising for biomedical applications after the evaluations of both the mechanical and the biological properties. PMID- 26275507 TI - Pathways involving traumatic losses, worry about family, adult separation anxiety and posttraumatic stress symptoms amongst refugees from West Papua. AB - There is some evidence that adult separation anxiety disorder (ASAD) symptoms are closely associated with posttraumatic stress disorder (PTSD) amongst refugees exposed to traumatic events (TEs), but the pathways involved remain to be elucidated. A recent study suggests that separation anxiety disorder precedes and predicts onset of PTSD. We examined a path model testing whether ASAD symptoms and worry about family mediated the path from traumatic losses to PTSD symptoms amongst 230 refugees from West Papua. Culturally adapted measures were applied to assess TE exposure and symptoms of ASAD and PTSD. A structural equation model indicated that ASAD symptoms played an important role in mediating the effects of traumatic losses and worry about family in the pathway to PTSD symptoms. Although based on cross-sectional data, our findings suggest that ASAD symptoms may play a role in the path from traumatic losses to PTSD amongst refugees. We propose an evolutionary model in which the ASAD and PTSD reactions represent complementary survival responses designed to protect the individual and close attachments from external threats. PMID- 26275508 TI - Agrobacterium tumefaciens-mediated transformation of the entomopathogenic fungus Nomuraea rileyi. AB - An Agrobacterium-mediated genetic transformation system for the entomopathogenic fungus Nomuraea rileyi was established. Three binary T-DNA vectors, pPZP-Hph, pPZP-Hph-RNAi and pPZP-Hph-DsRed2, were constructed. The trpc promoter from Aspergillus nidulans was used as the cis-regulatory element to drive the expression of hygromycin phosphotransferase (hph) gene and DsRed2, which conferred the hygromycin B (Hyg B) resistance and red fluorescence visualization, respectively. The blastospores and conidia were used as the recipients. The blastospores' transformation efficiency reached ~20-40 transformants per 10(6) blastospores, whereas the conidia were not transformed. Based on an analysis of five generations of subcultures, PCR and Southern blotting assays, the Ptrpc-hph cassette had integrated into the genomes of all transformants, which contained single copy of the hph gene and showed mitotic stability. Abundant altered morphologic phenotypes in colonies, blastospores and hyphae formations were observed in the arbitrary insertional mutants of N. rileyi, which made it possible to study the relationships between the functions and the interrupted genes over the whole genome. The transformation protocol will promote the functional characterization of genes, and the construction of genetically engineered strains of this important entomopathogenic fungus, and potentially of other similar fungal pathogens. PMID- 26275509 TI - Editorial to the Special issue: Psychological interventions for depression: A roadmap to stable remission. PMID- 26275510 TI - Ventilation/Perfusion Positron Emission Tomography--Based Assessment of Radiation Injury to Lung. AB - PURPOSE: To investigate (68)Ga-ventilation/perfusion (V/Q) positron emission tomography (PET)/computed tomography (CT) as a novel imaging modality for assessment of perfusion, ventilation, and lung density changes in the context of radiation therapy (RT). METHODS AND MATERIALS: In a prospective clinical trial, 20 patients underwent 4-dimensional (4D)-V/Q PET/CT before, midway through, and 3 months after definitive lung RT. Eligible patients were prescribed 60 Gy in 30 fractions with or without concurrent chemotherapy. Functional images were registered to the RT planning 4D-CT, and isodose volumes were averaged into 10-Gy bins. Within each dose bin, relative loss in standardized uptake value (SUV) was recorded for ventilation and perfusion, and loss in air-filled fraction was recorded to assess RT-induced lung fibrosis. A dose-effect relationship was described using both linear and 2-parameter logistic fit models, and goodness of fit was assessed with Akaike Information Criterion (AIC). RESULTS: A total of 179 imaging datasets were available for analysis (1 scan was unrecoverable). An almost perfectly linear negative dose-response relationship was observed for perfusion and air-filled fraction (r(2)=0.99, P<.01), with ventilation strongly negatively linear (r(2)=0.95, P<.01). Logistic models did not provide a better fit as evaluated by AIC. Perfusion, ventilation, and the air-filled fraction decreased 0.75 +/- 0.03%, 0.71 +/- 0.06%, and 0.49 +/- 0.02%/Gy, respectively. Within high-dose regions, higher baseline perfusion SUV was associated with greater rate of loss. At 50 Gy and 60 Gy, the rate of loss was 1.35% (P=.07) and 1.73% (P=.05) per SUV, respectively. Of 8/20 patients with peritumoral reperfusion/reventilation during treatment, 7/8 did not sustain this effect after treatment. CONCLUSIONS: Radiation-induced regional lung functional deficits occur in a dose-dependent manner and can be estimated by simple linear models with 4D V/Q PET/CT imaging. These findings may inform future studies of functional lung avoidance using V/Q PET/CT. PMID- 26275511 TI - Insight into the three-dimensional structure of maize chlorotic mottle virus revealed by Cryo-EM single particle analysis. AB - Maize chlorotic mottle virus (MCMV) is the only member of the Machlomovirus genus in the family Tombusviridae. Here, we obtained the Cryo-EM structure of MCMV by single particle analysis with most local resolution at approximately 4 A. The Calpha backbone was built based on residues with bulky side chains. The resolved C-terminus of the capsid protein subunit and obvious openings at the 2-fold axis demonstrated the compactness of the asymmetric unit, which indicates an important role in the stability of MCMV. The Asp116 residue from each subunit around the 5 fold and 3-fold axes contributed to the negative charges in the centers of the pentamers and hexamers, which might serve as a solid barrier against the leakage of genomic RNA. Finally, the loops most exposed on the surface were analyzed and are proposed to be potential functional sites related to MCMV transmission. PMID- 26275512 TI - Ocular injury in the United States: Emergency department visits from 2006-2011. AB - INTRODUCTION: Ocular complaints represent a sizeable burden to emergency departments, accounting for an estimated 2.4 million ED visits annually. We sought to characterise visits associated with ocular injury and examine factors contributing to inpatient admission. METHODS: We searched the Nationwide Emergency Department Sample between 2006 and 2011 and identified cases in which patients presented with a primary or secondary diagnosis of ocular trauma. We described these cases according to age, sex, external mechanism of injury, payer status, and identified relationships between these variables. Logistic regression models were employed to identify crude and adjusted relative odds of admission to inpatient status based on patient demographics, mechanism of injury, payer status, and the existence of multiple injuries. RESULTS: Between 2006 and 2011, a total of 5541,434 visits were made to EDs in the United States with a primary or other diagnosis of ocular trauma; ocular trauma was the primary diagnosis in 77.9% of these cases. Overall, mean age at presentation was 33.8 years and the majority of patients were male (64.8%). Male sex, older age, being struck by or against an object, the existence of multiple injuries, and Medicaid as a primary payer were all associated with significantly higher odds of hospital admission. DISCUSSION: The distribution of primary external mechanism of injury suggested that individuals are at higher risks for different injury types at each successive stage of life. Age and injury mechanism were correlated with odds of admission to inpatient status, with the highest odds among older adults who had been injured by being struck by or against an object. CONCLUSIONS: Ocular injury plays a substantial role in the ED. Further work is necessary to determine whether developing and implementing age- and sex-appropriate prevention strategies could reduce the incidence of ocular injury and reduce morbidity related to these types of injuries. PMID- 26275513 TI - Predictors of mortality for complex fractures of the pelvic ring in the elderly: a twelve-year review from a German level I trauma center. AB - STUDY OBJECTIVE: To document mortality rate and predictors of mortality in elderly patients with complex pelvic fractures. METHODS: We reviewed a total of 84 subjects whose ages were above 70 years with complex pelvic fractures, admitted to our hospital from January 2001 to December 2012. A multivariate linear regression model was used to determine the predictors of mortality in the study population. The median age of the patients was 80.4 years (range 70-94 years). 65 of 84 (77%) patients were females. There were 72 Tile Type B fractures (86%) and 12 Type C fractures (14%). The most common associated injuries were thoracic, extremity and head injuries, with incidence of 13 (15%), 11 (13%), and 9 (11%), respectively. RESULTS: The mortality rate was 10% in our study population. The initial haemoglobin on admission (p<0.01), the presence of blood vessel injuries (p<0.01) and the number of PRBCs transfused within the first six hours after admission (p<0.01) independently predicted mortality in elderly patients with complex pelvic fractures. CONCLUSION: Although there is a downward trend in mortality in elderly patients with complex pelvic fractures, haemodynamic instability still has a significant impact on survival of those patients. PMID- 26275514 TI - Carperitide Increases the Need for Renal Replacement Therapy After Cardiovascular Surgery. AB - OBJECTIVES: Acute kidney injury is a common complication after aortic surgery. Carperitide, a human atrial natriuretic peptide, was reported to be effective for preventing acute kidney injury after cardiac surgery. However, most studies were from single centers, and results of meta-analyses are subject to publication bias. The aim of the present study was to investigate whether carperitide preserved renal function in patients undergoing cardiovascular surgery. DESIGN: Retrospective cohort study. SETTING: Participating hospitals (N = 281) in a national database from 2010 to 2013. PARTICIPANTS: Adult patients (N = 47,032) who underwent cardiovascular surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main intervention variable investigated was the use of carperitide on the day of surgery. Assessed outcomes included receiving renal replacement therapy within 21 days of surgery and in-hospital mortality. Data were available for 47,032 patients, of whom 2,186 (4.6%) received carperitide on the day of surgery. Multivariate logistic regression analysis revealed that carperitide was significantly associated with a greater likelihood of receiving renal replacement therapy within 21 days of surgery, but not with in-hospital mortality. CONCLUSIONS: In patients undergoing cardiovascular surgery, carperitide significantly increased the odds of receiving renal replacement therapy within 21 days after surgery. PMID- 26275515 TI - Mechanism of Torrential Aortic Valve Insufficiency in Endocarditis: Leaflet Destruction, Restriction, Prolapse, or Perforation? PMID- 26275516 TI - Continuous Intraoperative Cefazolin Infusion May Reduce Surgical Site Infections During Cardiac Surgical Procedures: A Propensity-Matched Analysis. AB - OBJECTIVES: The authors sought to determine whether an institutional transition from intermittent to continuous dosing of intraoperative antibiotics in cardiac surgery affected surgical site infection (SSI) outcomes. DESIGN: A retrospective chart review utilizing propensity matching. SETTING: A single academic, tertiary care hospital. PARTICIPANTS: One thousand one hundred seventy-nine patients undergoing coronary artery bypass grafting (CABG) and/or cardiac valvular surgery between April 2013 and November 2014 who received perioperative cefazolin. INTERVENTIONS: By method of cefazolin administration, patients were divided into an "intermittent-dosing" (ID) group and a "continuous-infusion" (CI) group. MEASUREMENTS AND MAIN RESULTS: Of the 1,179 patients who underwent cardiac surgery during the study period, 1:1 propensity score matching yielded 399 patients in each group. Rates of diabetes (33.6% ID v 33.8% CI, p = 0.94), coronary artery bypass (62.3% v 61.4%, p = 0.66), and bilateral internal mammary artery harvesting (6.0% v 8.3%, p = 0.22) were similar between groups. SSIs occurred in more ID patients than CI patients (2.3% v 0.5%, p = 0.03). This difference was driven by decreases in extremity and conduit harvest site SSIs (1.8% v 0.3%, p = 0.03), as there were no episodes of mediastinitis, and superficial sternal SSI rates did not differ (0.5% v 0.3%, p = 0.56). There also were significantly fewer episodes of pneumonia in the CI group (6.0% v 2.3%, p = 0.008). Intensive care unit and total lengths of stay did not differ. Thirty-day mortality was 2.8% in both groups (p = 1.00). CONCLUSIONS: As compared to ID regimens, CI cefazolin infusion may reduce post-cardiac surgery infectious complications. Further study in larger patient populations is needed. PMID- 26275517 TI - Moderate Aortic Stenosis and Coronary Artery Bypass Grafting: Clinical Update for the Perioperative Echocardiographer. AB - Incidental aortic stenosis in the setting of coronary artery bypass surgery may be a perioperative challenge. The accurate assessment of the degree of aortic stenosis remains an important determinant. Although severe aortic stenosis is an indication for valve replacement, current guidelines advise a balanced approach to the management of moderate aortic stenosis in this setting. Multiple factors should be considered in a team discussion to balance risks versus benefits for the various management options in the given patient. The rapid progress in aortic valve technologies also offer alternatives for definitive management of moderate aortic stenosis in this setting that will likely become even safer in the near future. PMID- 26275518 TI - Risk Stratification in Off-Pump Coronary Artery Bypass (OPCAB) Surgery-Role of EuroSCORE II. AB - OBJECTIVES: To evaluate the EuroSCORE II for risk stratification in patients undergoing off-pump coronary artery bypass (OPCAB) surgery. DESIGN: A retrospective observational study. SETTING: Two tertiary care hospitals. PARTICIPANTS: Participants were 1,211 patients undergoing OPCAB surgery. INTERVENTIONS: No interventions were implemented. MEASUREMENTS AND MAIN RESULTS: The EuroSCORE II estimated the operative risk for each patient. The calibration of the scoring system was assessed using the Hosmer Lemeshow test, and the discriminative capacity was estimated with area under receiver operating characteristic curves. The incidence, patient characteristics, causes of intraoperative conversion to on-pump coronary artery bypass (ONCAB), and outcome were studied. The all-cause in-hospital mortality was 2.39%. Predicted mortality with the EuroSCORE II was 2.03+/-1.63. Using the Hosmer Lemeshow test, a C statistic of 8.066 (p = 0.472) was obtained, indicating satisfactory model fit. The calculated area under the receiver operating characteristic curve was 0.706 (p = 0.0002), indicating good discriminatory power. Emergency intraoperative conversion to ONCAB occurred in 6.53% of patients. The mortality in the ONCAB group was significantly higher compared with patients who underwent successful OPCAB surgery (15.18% v 1.5%, p<0.0001). On multiple regression analysis with conversion to ONCAB as the endpoint, associated factors were patients with a higher EuroSCORE II (odds ratio = 1.13, confidence interval = 1.03-1.27) and more than-trivial mitral regurgitation (odds ratio = 1.84, confidence interval = 1.07 3.06). Net reclassification improvement of 0.714 (p<0.0001) was obtained when on pump conversion was added to the EuroSCORE II. CONCLUSIONS: The EuroSCORE II has satisfactory calibration and discrimination power to predict mortality after OPCAB surgery. Intraoperative conversion to ONCAB is a major complication of OPCAB surgery. A higher EuroSCORE II also predicts higher probability of conversion to ONCAB. PMID- 26275519 TI - Novel Presentation of Flail Mitral Valve. PMID- 26275520 TI - Aortic Valve Papillary Fibroelastoma: An Insidious and Unusual Cause of Angina. PMID- 26275521 TI - Acute Kidney Injury in Patients Undergoing Open Abdominal Aortic Aneurysm Repair: A Pilot Observational Trial. AB - OBJECTIVES: Acute kidney injury (AKI) is a frequent complication after open repair of abdominal aortic aneurysms (AAA). Little research has been done to determine whether intraoperative hemodynamic events may precipitate AKI. Novel biomarkers also may aid in the earlier diagnosis of AKI. DESIGN: A pilot prospective observational trial. SETTING: A single tertiary academic medical center. PARTICIPANTS: Participants were 40 adult patients undergoing open repair of infrarenal AAA. INTERVENTIONS: Intraoperative hemodynamic monitoring of heart rate, mean arterial pressure, central venous pressure, and cardiac index was performed on a continuous basis. Blood samples were obtained at baseline and at 24 hours postoperatively for inflammatory biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL). MEASUREMENTS AND MAIN RESULTS: AKI occurred in 20% of patients (8 of 40). Hypotension, including duration (defined as the length of time mean arterial pressure was<65 mmHg) and magnitude (the area under the curve of a mean arterial pressure<65 mmHg), was the only factor associated with postoperative AKI. Urinary NGAL at the conclusion of surgery had excellent ability to predict the development of AKI (area under the curve 0.84, 95% confidence interval = 0.70-0.97). The cytokines pentraxin 3 (PTX3), interleukin-1 receptor antagonist (IL1-RA), macrophage chemotactic protein (MCP), suppressor of tumorigenicity 2 (ST-2), and interleukin-10 (IL-10) also had good ability to predict the development of AKI in the immediate postoperative period. CONCLUSIONS: AKI occurs frequently in patients undergoing open repair of AAA. Intraoperative hypotension was the only factor that predicted the development of subsequent AKI. Urinary NGAL and several novel inflammatory biomarkers demonstrated good ability to predict its development. Novel biomarkers also may aid in the early diagnosis of AKI. PMID- 26275522 TI - Levosimendan Treatment for Heart Failure: A Systematic Review and Meta-Analysis. AB - OBJECTIVE: Emerging studies suggest that administration of levosimendan therapy may be better than dobutamine or placebo in decompensated heart failure. The authors performed an updated meta-analysis of trials to obtain the best estimates of the efficacy and safety of levosimendan for the initial treatment of decompensated heart failure. DESIGN: A meta-analysis. SETTING: Hospitals. PARTICIPANTS: A total of 5,349 patients from 25 randomized controlled studies were included in the analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors performed a meta-analysis of trials comparing levosimendan therapy with dobutamine or placebo in patients with decompensated heart failure. Twenty-five trials, involving 5,349 patients, were included. Two reviewers performed independent article review and study quality assessment. Data on overall mortality, early-term mortality, midterm mortality, long-term mortality, efficacy outcomes, and adverse events were collected. Mortality outcomes were according to follow-up duration: early term (<=30-day), midterm (30-day to<=6 month), and long term (>6-month). Levosimendan was compared with dobutamine or placebo, calculating pooled relatives risk (RRs) and associated 95% confidence intervals (CIs). A random-effects model was selected for meta-analysis if there was significant heterogeneity. Levosimendan significantly reduced total mortality (17.1% versus 20.8%; RR, 0.84; 95% CI, 0.75-0.94). Compared with dobutamine, levosimendan was associated with significant reduction in mortality at final follow-up (RR, 0.86; 95% CI, 0.76-0.97; I(2) = 7%; p = 0.02).Compared with placebo, levosimendan was associated with a nonsignificant trend in favor of placebo in mortality at final follow-up (11.6% versus 16.2%, RR, 0.75; 95% CI, 0.56-1.01; p = 0.06), but it was associated with a significant reduction in long term mortality (RR, 0.34; 95%CI, 0.15-0.76; p = 0.009). Compared with dobutamine or placebo, levosimendan therapy was associated with improvements in hemodynamically- and echocardiographically-derived cardiac parameters. Levosimendan therapy increased the risks of extrasystoles (RR, 1.88; 95% CI, 1.26 2.81), hypotension (RR, 1.33; 95% CI, 1.15-1.53), and headache or migraine (RR, 1.94; 95% CI, 1.54-2.43) when compared with control therapy. CONCLUSIONS: As compared to placebo or dobutamine, levosimendan in patients with heart failure seemed to have hemodynamic and cardiac benefits. It reduced total mortality and was associated with an increased risk of cardiovascular adverse events. PMID- 26275523 TI - Echocardiography Is Essential in Detection of Cardiac Tamponade Due to Sliding Hiatal Hernia. PMID- 26275524 TI - Preface. Microbial Fuel Cells. PMID- 26275525 TI - Car driver attitudes, perceptions of social norms and aggressive driving behaviour towards cyclists. AB - The interaction of car drivers and cyclists is one of the main causes of cycle incidents. The role of attitudes and social norms in shaping car drivers' aggressive behaviour towards cyclists, is not well understood and merits investigation. A sample of 276 drivers completed an online questionnaire concerning their attitudes towards cyclists, attitudes towards risky driving, perception of social norms concerning aggressive driving towards cyclists, and the frequency with which they engage in such aggressive driving behaviours. The results showed that attitudes towards cyclists, as well as social norm perceptions concerning aggressive driving towards cyclists, were associated with aggressive driving towards cyclists. Negative attitudes towards cyclists were more pronounced in non-cyclists than cyclists and their association with aggressive driving behaviour was stronger in cyclists than non-cyclists. The perception of social norms concerning aggressive driving towards cyclists had a stronger association with aggressive driving in non-cyclists than cyclists. Attitudes towards risk taking did not affect aggressive driving towards cyclists. These findings can inform campaigns that aim to improve cyclist and car driver interaction on the roads, making them safer to use for cyclists. PMID- 26275526 TI - A Singlet Thiophosphoryl Nitrene and Its Interconversion with Thiazyl and Thionitroso Isomers. AB - Thiophosphoryl nitrenes, R2P(S)N, are thiazirine-like intermediates that have been chemically inferred from trapping products in early solution studies. In this work, photolysis of the simplest thiophosphoryl azide, F2P(S)N3, in solid noble-gas matrices enabled a first-time spectroscopic (IR and UV-vis) identification of the thiophosphoryl nitrene F2P(S)N in its singlet ground state. Upon visible-light irradiation (>=495 nm), it converts into the thionitroso isomer F2P-N?S, which can also be produced in the gas phase from flash vacuum pyrolysis of F2P(S)N3. Further irradiation of F2P-NS with 365 nm UV light leads to the reformation of F2P(S)N and isomerization to the thiazyl species F2P-S=N. PMID- 26275527 TI - Enhanced production of (R,R)-2,3-butanediol by metabolically engineered Klebsiella oxytoca. AB - Microbial fermentation produces a racemic mixture of 2,3-butanediol ((R,R)-BD, (S,S)-BD, and meso-BD), and the compositions and physiochemical properties vary from microorganism to microorganism. Although the meso form is much more difficult to transport and store because of its higher freezing point than those of the optically active forms, most microorganisms capable of producing 2,3-BD mainly yield meso-2,3-BD. Thus, we developed a metabolically engineered (R,R)-2,3 BD overproducing strain using a Klebsiella oxytoca DeltaldhA DeltapflB strain, which shows an outstanding 2,3-BD production performance with more than 90 % of the meso form. A budC gene encoding 2,3-BD dehydrogenase in the K. oxytoca DeltaldhA DeltapflB strain was replaced with an exogenous gene encoding (R,R)-2,3 BD dehydrogenase from Paenibacillus polymyxa (K. oxytoca DeltaldhA DeltapflB DeltabudC::PBDH strain), and then its expression level was further amplified with using a pBBR1MCS plasmid. The fed-batch fermentation of the K. oxytoca DeltaldhA DeltapflB DeltabudC::PBDH (pBBR-PBDH) strain with intermittent glucose feeding allowed the production of 106.7 g/L of (R,R)-2,3-BD [meso-2,3-BD, 9.3 g/L], with a yield of 0.40 g/g and a productivity of 3.1 g/L/h, which should be useful for the industrial application of 2,3-BD. PMID- 26275528 TI - Directed optimization of a newly identified squalene synthase from Mortierella alpine based on sequence truncation and site-directed mutagenesis. AB - Terpenoids, a class of isoprenoids usually isolated from plants, are always used as commercial flavor and anticancer drugs. As a key precursor for triterpenes and sterols, biosynthesis of squalene (SQ) can be catalyzed by squalene synthase (SQS) from two farnesyl diphosphate molecules. In this work, the key SQS gene involved in sterols synthesis by Mortierella alpine, an industrial strain often used to produce unsaturated fatty acid such as gamma-linolenic acid and arachidonic acid, was identified and characterized. Bioinformatic analysis indicated that MaSQS contained 416 amino acid residues involved in four highly conserved regions. Phylogenetic analysis revealed the closest relationship of MaSQS with Ganoderma lucidum and Aspergillus, which also belonged to the member of the fungus. Subsequently, the recombinant protein was expressed in Escherichia coli BL21(DE3) and detected by SDS-PAGE. To improve the expression and solubility of protein, 17 or 27 amino acids in the C-terminal were deleted. In vitro activity investigation based on gas chromatography-mass spectrometry revealed that both the truncated enzymes could functionally catalyze the reaction from FPP to SQ and the enzymatic activity was optimal at 37 degrees C, pH 7.2. Moreover, based on the site-directed mutagenesis, the mutant enzyme mMaSQSDeltaC17 (E186K) displayed a 3.4-fold improvement in catalytic efficiency (k(cat)/K(m)) compared to the control. It was the first report of characterization and modification of SQS from M. alpine, which facilitated the investigation of isoprenoid biosynthesis in the fungus. The engineered mMaSQSDeltaC17 (E186K) can be a potential candidate of the terpenes and steroids synthesis employed for synthetic biology. PMID- 26275530 TI - Antibody-Drug Conjugates. PMID- 26275529 TI - In vivo Functional Evaluation of Increased Brain Delivery of the Opioid Peptide DAMGO by Glutathione-PEGylated Liposomes. AB - PURPOSE: The purpose of this study was to evaluate formulation factors causing improvement in brain delivery of a small peptide after encapsulation into a targeted nanocarrier in vivo. METHODS: The evaluation was performed in rats using microdialysis, which enabled continuous sampling of the released drug in both the brain (striatum) and blood. Uptake in brain could thereby be studied in terms of therapeutically active, released drug. RESULTS: We found that encapsulation of the peptide DAMGO in fast-releasing polyethylene glycol (PEG)ylated liposomes, either with or without the specific brain targeting ligand glutathione (GSH), doubled the uptake of DAMGO into the rat brain. The increased brain delivery was observed only when the drug was encapsulated into the liposomes, thus excluding any effects of the liposomes themselves on the blood-brain barrier integrity as a possible mechanism. The addition of a GSH coating on the liposomes did not result in an additional increase in DAMGO concentrations in the brain, in contrast to earlier studies on GSH coating. This may be caused by differences in the characteristics of the encapsulated compounds and the composition of the liposome formulations. CONCLUSIONS: We were able to show that encapsulation into PEGylated liposomes of a peptide with limited brain delivery could double the drug uptake into the brain without using a specific brain targeting ligand. PMID- 26275531 TI - Phase I trial of combination of FOLFIRI and pasireotide, a somatostatin analogue, in advanced gastrointestinal malignancies. AB - INTRODUCTION: Pasireotide (SOM230) is a somatostatin analog with high binding affinity for somatostatin receptors including sst1, 2, 3 and 5 and inhibit insulin like growth factor-1. Blocking of IGF-1 receptor (IGF-1R) in combination with cytotoxic chemotherapy has demonstrated additive or synergistic activity in pre-clinical models. This study aimed to evaluate the maximum tolerated dose (MTD) of pasireotide in combination with standard FOLFIRI (5-fluorouracil, leucovorin and irinotecan) regimen in patients with gastrointestinal malignancies. METHODS: This was a phase 1, 3 + 3 design, open-label dose escalation study conducted in sequential cohorts to determine the MTD of pasireotide in combination with FOLFIRI. All patients had gastrointestinal malignancies and were previously treated. Sixteen patients enrolled in five dose cohorts at pasireotide doses of 40, 60, 80, 100 and 120 mg were evaluated for safety and tolerability of the combination. RESULTS: The tumor types of the enrolled subjects included esophageal (n = 5), biliary tract (n = 3), colon (n = 3), gastric (n = 2), pancreatic (n = 1), anal (n = 1) and small bowel (n = 1). No dose limiting toxicities were observed. The most common adverse events related to the study treatment included hyperglycemia (81 %), neutropenia (62 %), thrombocytopenia (44 %), anorexia (44 %), dehydration (25 %) and elevated alkaline phosphatase (25 %). Two patients had partial response and 7 patients had stable disease. Plasma levels of IGF-1 and IGFBP-3 were significantly reduced after treatment with pasireotide. DISCUSSION: Combination of pasireotide and FOLFIRI has manageable safety profile and is feasible in patients with gastrointestinal malignancies. Preliminary signals of activity were observed. Larger phase II trials are warranted. PMID- 26275533 TI - Fundamental Use of Surgical Energy (FUSE) certification: validation and predictors of success. AB - INTRODUCTION: The Fundamental Use of Surgical Energy (FUSE) program includes a Web-based didactic curriculum and a high-stakes multiple-choice question examination with the goal to provide certification of knowledge on the safe use of surgical energy-based devices. The purpose of this study was (1) to set a passing score through a psychometrically sound process and (2) to determine what pretest factors predicted passing the FUSE examination. METHODS: Beta-testing of multiple-choice questions on 62 topics of importance to the safe use of surgical energy-based devices was performed. Eligible test takers were physicians with a minimum of 1 year of surgical training who were recruited by FUSE task force members. A pretest survey collected baseline information. RESULTS: A total of 227 individuals completed the FUSE beta-test, and 208 completed the pretest survey. The passing/cut score for the first test form of the FUSE multiple-choice examination was determined using the modified Angoff methodology and for the second test form was determined using a linear equating methodology. The overall passing rate across the two examination forms was 81.5%. Self-reported time studying the FUSE Web-based curriculum for a minimum of >2 h was associated with a passing examination score (p < 0.001). Performance was not different based on increased years of surgical practice (p = 0.363), self-reported expertise on one or more types of energy-based devices (p = 0.683), participation in the FUSE postgraduate course (p = 0.426), or having reviewed the FUSE manual (p = 0.428). Logistic regression found that studying the FUSE didactics for >2 h predicted a passing score (OR 3.61; 95% CI 1.44-9.05; p = 0.006) independent of the other baseline characteristics recorded. CONCLUSION(S): The development of the FUSE examination, including the passing score, followed a psychometrically sound process. Self-reported time studying the FUSE curriculum predicted a passing score independent of other pretest characteristics such as years in practice and self-reported expertise. PMID- 26275532 TI - Laparoscopy-assisted open cystogastrostomy and pancreatic debridement for necrotizing pancreatitis (with video). AB - INTRODUCTION: Pancreatic pseudocysts and walled-off necrosis are well-known complications, described in 10% of cases of acute pancreatitis. Open cystogastrostomy is usually proposed after failure of minimally invasive drainage or in the presence of septic shock. The objective of this study was to evaluate the feasibility and efficacy of laparoscopy-assisted open cystogastrostomy for treatment of symptomatic pancreatic pseudocyst with pancreatic necrosis. MATERIALS AND METHODS: Between January 2011 and October 2014, all patients with pseudocyst and pancreatic necrosis undergoing open cystogastrostomy were included. Surgical procedure was standardized. The primary efficacy endpoint was the feasibility and efficacy of laparoscopy-assisted open cystogastrostomy as treatment of symptomatic pancreatic pseudocyst. Secondary endpoints included demographic data, preoperative management, operative data, postoperative data and follow-up. RESULTS: Laparoscopy-assisted open cystogastrostomy was performed in 11 patients [six men (54%)], with a median age of 61 years (45-84). Nine patients received preoperative radiological or endoscopic management. First-line open cystogastrostomy was performed in two cases. Median operating time was 190 min (110-240). There was one intraoperative complication related to injury of a branch of the superior mesenteric vein. There were no postoperative deaths and two postoperative complications (18%) including one major complication (postoperative bleeding). The median length of hospital stay after surgery was 16 days (7-35). The median follow-up was 10 months (2-45). One patient experienced recurrence during follow-up. CONCLUSION: Open cystogastrostomy for necrotizing pancreatitis promotes adequate internal drainage with few postoperative complications and a short length of hospital stay. However, this technique must be performed very cautiously due to the risk of vascular injury which can be difficult to repair in the context of severe local inflammation related to pancreatic necrosis. PMID- 26275534 TI - Laparoscopic sigmoid colectomy for complicated diverticulitis is safe: review of 576 consecutive colectomies. AB - INTRODUCTION: Laparoscopic resection of diverticular disease is typically offered to selected patients. We present the outcomes of laparoscopic colectomy in consecutive patients suffering from either simple diverticulitis (SD) or complicated diverticulitis (CD). PURPOSE: To examine the outcomes of laparoscopic sigmoid colectomy for complicated diverticulitis. METHODS: Between December 2001 and May 2013, all patients with diverticulitis requiring elective operation were offered laparoscopic sigmoid colectomy as the initial approach. All cases were managed at a large tertiary care center on the colorectal surgery service. Preoperative, intraoperative, and postoperative variables were prospectively entered into the colorectal surgery service database (CRSD) and analyzed retrospectively. RESULTS: Of the 576 patients in the CRSD, 139 (24.1%) had CD. The overall conversion rate was 12.8% (n = 74). The average BMI was 29.8 kg/m(2). The conversion rate for CD was 12.2%. The return of bowel function time was delayed in the CD group when compared to the SD group (3.1 vs 3.8 days, p = 0.04). The hospital length of stay (HLOS) was similar between the groups (5.1 vs 5.8 days, p = 0.08). The overall anastomotic leak rate was 2.1% (n = 12). Patients undergoing laparoscopic resection for SD had a postoperative complication rate of 10.0% (n = 38), whereas those with CD had a postoperative morbidity rate of 19.6% (n = 24). CD patients who had conversion to an open procedure had an even higher rate of postoperative complications (29.4%, n = 5, p = 0.35). On non-parsimonious multivariate adjustment, only CD (RR 1.96, 95% CI 1.11-3.46, p = 0.02) was found to be an independent risk factor for the development of postoperative complications. CONCLUSIONS: Complicated diverticulitis did not affect the conversion rate to an open procedure. However, patients with CD are prone to postoperative complications. The laparoscopic approach to sigmoid colectomy is safe and preferable in experienced hands. PMID- 26275535 TI - Electrocautery device does not provide adequate pulmonary vessel sealing in transumbilical anatomic pulmonary lobectomy. AB - INTRODUCTION: Safe pulmonary vessel sealing device plays a crucial role in anatomic lung resection. In 2014, we reported high rates of massive bleeding complications during transumbilical lobectomy in a canine model due to difficulty in managing the pulmonary vessel with an endostapler. In this animal survival series, we aimed to evaluate the outcome of pulmonary vessel sealing with an electrocautery device to simplify the transumbilical thoracic surgery. METHODS: Under general anesthesia, a 3-cm longitudinal incision was made over the umbilicus. Under video guidance, a bronchoscope was inserted through the incision for exploration. The diaphragmatic wound was created with an electrocautery knife and used as the entrance into the thoracic cavity. Using the transumbilical technique, anatomic lobectomy was performed with electrosurgical devices and endoscopic vascular staplers in 15 canines. RESULTS: Transumbilical endoscopic anatomic lobectomy was successfully completed in 12 of the 15 animals. Intraoperative bleeding developed in three animals during pulmonary hilum dissection, where one animal was killed due to hemodynamic instability and the other two animals required thoracotomy to complete the operation. There were five delayed bleeding and surgical mortality cases caused by inadequate vessel sealing by electrosurgical devices. Postmortem examination confirmed correct transumbilical lobectomy in the twelve animals that survived the operations. CONCLUSION: Transumbilical anatomic lobectomy is technically feasible in a canine model; however, the electrosurgical devices were not effective in sealing the pulmonary vessel in the current canine model. PMID- 26275536 TI - Trangastric endo-organ resection of a proximal gastric lesion. AB - INTRODUCTION: Gastric tumors confined to mucosa and submucosa can be resected with endoscopic resection techniques. They include endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) [1, 2]. These techniques can be challenging when the tumor is large or is near the gastroesophageal (GE) junction. Transgastric resection is a novel technique of removing gastric tumors that are unresectable by endoscopy due to their size and location. MATERIALS AND METHODS: We present a case of a 41-year-old male where a suspicious appearing lesion near the GE junction was removed using combined trans-gastric laparoscopic and endoscopic technique. The stomach was inflated using endoscopy, and three 5 mm balloon-tipped trocars were inserted directly into the stomach. The lesion was lifted with submucosal injection of saline and was resected using ultrasonic dissection device. The specimen was retrieved using Rothnet through the endoscope. The mucosal defect was closed with absorbable sutures. Trocars were removed and gastrostomy sites were closed with Endostitch device. Swallow study done on post-op day 2 did not show any signs of leak. Patient was discharged home on post-op day 5. Final pathology was consistent with hyperplastic polyp. CONCLUSION: Proximal Gastric lesions can be safely removed with combined Laparoscopic trans-gastric and endoscopic approach. PMID- 26275537 TI - Long-term outcomes of combined endoscopic/laparoscopic intragastric enucleation of presumed gastric stromal tumors. AB - PURPOSE: Definitive surgical treatment of gastric myogenic neoplasms such as gastrointestinal stromal tumors (GISTs) typically involves full-thickness resection of the lesion with normal gastric wall as the margin. This is not readily possible with proximal gastric lesions near the gastroesophageal junction, nor necessary for small incidental lesions. We have employed a combined endoscopic/laparoscopic intraluminal enucleation technique for selected patients and report long-term surveillance following this novel technique. METHODS: Retrospective review of patients who have undergone intraluminal laparoscopic resection from 1994 to 2008. RESULTS: Fifteen patients who underwent intraluminal enucleation were followed up for a median of 61 months. There were eight men and seven women with a mean age of 62.1 +/- 3.38 years. Eight patients (53 %) underwent endoscopy for gastrointestinal bleeding, six for dyspepsia (40 %), six for anemia (40 %), and four for abdominal pain (27 %). Eight lesions (53 %) were located in the fundus/cardia: six (40 %) in the body and two (13 %) in the antrum. The mean tumor size was 3.5 +/- 0.45 (1.5-7.0) cm. GIST lesions with benign histologic features predominated. All operations were successfully completed, including full-thickness resections with no conversion to open procedure, major morbidity, or mortality. Complete endoscopic and endosonographic surveillance was accomplished in 14 patients with no local or distant recurrence and no symptomatic follow-up in any patient. CONCLUSION: Enucleation of intact gastrointestinal stromal tumors can be accomplished with low risk of recurrence when done with a combined endoscopic/laparoscopic intraluminal technique. It should be the preferred approach considered for small, proximal, intraluminal tumors. PMID- 26275539 TI - Revisional surgery after failed esophagogastric myotomy for achalasia: successful esophageal preservation. AB - BACKGROUND: Treatment failure with recurrent dysphagia after Heller myotomy occurs in fewer than 10 % of patients, most of whom will seek repeat surgical intervention. These reoperations are technically challenging, and as such, there exist only limited reports of reoperation with esophageal preservation. METHODS: We retrospectively reviewed the records of patients who sought operative intervention from March 1998 to December 2014 for obstructed swallowing after esophagogastric myotomy. All patients underwent a systematic approach, including complete hiatal dissection, takedown of prior fundoplication, and endoscopic assessment of myotomy. Patterns of failure were categorized as: fundoplication failure, inadequate myotomy, fibrosis, and mucosal stricture. RESULTS: A total of 58 patients underwent 65 elective reoperations. Four patients underwent esophagectomy as their initial reoperation, while three patients ultimately required esophagectomy. The remainder underwent reoperations with the goal of esophageal preservation. Of these 58, 46 were first-time reoperations; ten were second time; and two were third-time reoperations. Forty-one had prior operations via a trans-abdominal approach, 11 via thoracic approach, and 6 via combined approaches. All reoperations at our institution were performed laparoscopically (with two conversions to open). Inadequate myotomy was identified in 53 % of patients, fundoplication failure in 26 %, extensive fibrosis in 19 %, and mucosal stricture in 2 %. Intraoperative esophagogastric perforation occurred in 19 % of patients and was repaired. Our postoperative leak rate was 5 %. Esophageal preservation was possible in 55 of the 58 operations in which it was attempted. At median follow-up of 34 months, recurrent dysphagia after reoperation was seen in 63 % of those with a significant fibrosis versus 28 % with inadequate myotomy, 25 % with failed wrap, and 100 % with mucosal stricture (p = 0.10). CONCLUSIONS: Laparoscopic reoperation with esophageal preservation is successful in the majority of patients with recurrent dysphagia after Heller myotomy. The pattern of failure has implications for relief of dysphagia with reoperative intervention. PMID- 26275540 TI - The threatened stomach: management of the acute gastric volvulus. AB - INTRODUCTION: Acute presentation of gastric volvulus is a rare condition with a high mortality for acute ischaemia. This study was undertaken to investigate the acute management, diagnosis, and long-term outcomes of patients presenting with acute gastric volvulus. METHODS: Cases were reviewed retrospectively from 2004 to 2014. Patients presenting as an emergency admission with acute gastric volvulus were included. RESULTS: Thirty-six patients were included, five of whom had previous surgery. The mean age was 71 years old. All patients presented with vomiting and chest/epigastric pain. CT was diagnostic in all 26 patients. Barium swallow was diagnostic in two/four patients. OGD was diagnostic in 9 of 20 patients. All patients had an NG tube placed, and eight patients were treated conservatively and made a full recovery. Twenty-nine patients proceeded to surgery. Nine had a laparoscopic repair with two open conversions. Four patients had gastric necrosis, and all had open surgery with resection. Three patients had a mediastinal perforation, and one patient required an additional thoracotomy. All patients with viable stomach had a hiatal repair (where appropriate), 11 had a gastropexy, and 11 had a fundoplication. Mortality for gastric necrosis/perforation was 30 %. Mean postoperative stay was 4 days for laparoscopic repair and 8 days for uncomplicated open surgery. Nine of twenty nine had transient dysphagia postoperatively. Three of eight patients treated conservatively had an elective procedure subsequently. CONCLUSIONS: Acute paraoesophageal hiatus hernia requires early resuscitation and diagnosis. CT should be favoured in assessment, and an NG tube placed promptly. A conservative management may be considered safely in stable patients. Surgical management should be prompt for unstable patients. Gastric ischaemia or perforation has a mortality of 30 %. Laparoscopic repair has a shorter postoperative stay, but has a higher recurrence rate. Surgery for patients without gastric ischaemia has good long-term outcomes with minimal morbidity. PMID- 26275538 TI - Laparoscopic lateral pelvic lymph node dissection is achievable and offers advantages as a minimally invasive surgery over the open approach. AB - BACKGROUND: Laparoscopic lateral pelvic lymph node dissection (LPLD) is a minimally invasive alternative to open surgical therapy for advanced low rectal cancer patients. This study assessed potential risk factors for lateral pelvic lymph node metastasis (LPLM) and evaluated the feasibility and oncological safety of laparoscopic LPLD compared with the conventional open approach. METHODS: We retrospectively reviewed the clinical records of 90 patients with advanced low rectal cancer who underwent LPLD following total mesorectal excision at Kyushu University Hospital between January 2001 and July 2014. We compared the clinicopathological features between the patients with and without LPLM and the surgical outcomes between patients who underwent laparoscopic LPLD (LL) and open LPLD (OL). RESULTS: Fourteen (15.6 %) patients had LPLM. Univariate analysis revealed that undifferentiated cancer, positive lymphatic invasion, >50 % circumferential cancer extent, mesorectal lymph node metastases (MLM), and distant metastasis were associated with LPLM. In the multivariate analysis, MLM was the only independent risk factor for LPLM. Forty-six (51.1 %) patients underwent LL, and 44 (48.9 %) patients underwent OL. The mean surgical duration was longer in the LL group than in the OL group (641.0 vs. 312.0 min, P < 0.001). The LL group also had less hemorrhage (252.0 vs. 815.0 mL, P < 0.001) and a shorter hospital stay (22.9 vs. 29.1 days, P = 0.04) than the OL group. The mean number of harvested lateral pelvic lymph nodes was larger in the LL group than in the OL group (19.5 vs. 15.8, P < 0.05). The morbidity rate and overall survival (3-year OS: 94.7 vs. 82.9 %, P = 0.25) did not differ between the two groups. CONCLUSIONS: Patients with advanced low rectal cancer presenting MLM are good candidates for LPLD. Laparoscopic LPLD enables retrieval of more lymph nodes and may be acceptable for the treatment of advanced low rectal cancer. PMID- 26275541 TI - Laparoscopic surgery in middle- and low-income countries: gasless lift laparoscopic surgery. AB - INTRODUCTION: Surgically treatable conditions are an increasing burden in low- and middle-income countries, and recent studies suggest they have overtaken the "big three" (malaria, tuberculosis and HIV) as a cause of mortality. AIM: In this context, we have worked to modify standard laparoscopic equipment to allow laparoscopy in remote areas without support services such as bottled gases or disposable instruments. RESULTS: A simple and reliable system of gasless laparoscopy has been developed using robust reusable instruments, widening the potential availability of laparoscopic surgery in remote and rural areas. CONCLUSION: Our findings suggest that, using this equipment, appropriately trained surgeons can provide minimally invasive surgery in even the most remote locations. PMID- 26275542 TI - The First Decade of Laparoscopic Pancreaticoduodenectomy in the United States: Costs and Outcomes Using the Nationwide Inpatient Sample. AB - BACKGROUND: Minimally invasive pancreaticoduodenectomy (PD) remains an uncommon procedure, and the safety and efficacy remain uncertain beyond single institution case series. The aim of this study is to compare outcomes and costs between laparoscopic (LPD) and open PD (OPD) using a large population-based database. METHODS: The Nationwide Inpatient Sample database (a sample of approximately 20 % of all hospital discharges) was analyzed to identify patients who underwent PD from 2000 to 2010. Patient demographics, comorbidities, hospital characteristics, inflation-adjusted total charges, and complications were evaluated using univariate and multivariate logistic regression. Hospitals were categorized as high-volume hospitals (HVH) if more than 20 PD (open and laparoscopic) were performed annually, while those performing fewer than 20 PD were classified as low-volume hospitals. RESULTS: Of the 15,574 PD identified, 681 cases were LPD (4.4 %). Compared to OPD, patients who underwent LPD were slightly older (65 vs. 67 years; p = 0.001) and were more commonly treated at HVH (56.6 vs. 66.1 %; p < 0.001). Higher rates of complications were observed in OPD than LPD (46 vs. 39.4 %; p = 0.001), though mortality rates were comparable (5 vs. 3.8 %, p = 0.27). Inflation-adjusted median hospital charges were similar between OPD and LPD ($87,577 vs. $81,833, p = 0.199). However, hospital stay was slightly longer in the OPD group compared to LPD group (12 vs. 11 days, p < 0.001). Stratifying outcomes by hospital volume, LPD at HVH resulted in shorter hospital stays (9 vs. 13 days, p < 0.001), which translated into significantly lower median hospital charges ($76,572 vs. $106,367, p < 0.001). CONCLUSIONS: Contrary to fears regarding the potential for compromised outcomes early in the learning curve, LPD morbidity in its first decade is modestly reduced, while hospital costs are comparable to OPD. In high-volume pancreatic hospitals, LPD is associated with a reduction in length of stay and hospital costs. PMID- 26275543 TI - Weight-loss outcomes of SPIDER((r)) sleeve gastrectomy at 6 months compared to traditional laparoscopic technique. AB - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has become a primary stand alone procedure for weight-loss surgery. The standard technique for LSG involves several small abdominal incisions. The single port instrument delivery extended reach (SPIDER((r))) surgical system has been introduced as a single site modality. This technique has been described previously; however, weight-loss outcomes of SPIDER((r)) sleeve gastrectomy have not been compared to multi-port LSG. METHODS: We performed a retrospective review of a prospectively collected database. All cases were performed by a single surgeon between August 2011 and September 2013. Thirty-two patients underwent SPIDER((r)) sleeve gastrectomy, while 30 underwent LSG. Primary outcomes were change in BMI and percent excess weight loss (%EWL) at 6 months post-operatively. Secondary outcomes included: operative time, estimated blood loss (EBL), and complications. RESULTS: There were no demographic differences between cohorts except initial BMI (SPIDER((r)) = 42.1, LSG = 46.5, p < 0.001). Mean %EWL at 6 months post-operatively was higher in the SPIDER((r)) cohort (59.1 vs. 48.3 %, p < 0.005). Similarly there was a lower mean BMI at 6 months post-operatively in the SPIDER((r)) cohort (31.1 vs. 35.5, p < 0.0001). The net change in BMI for each cohort was equivalent (SPIDER((r)) = 11.1, LSG = 11.0, p = 0.95). Mean operative time was longer in SPIDER((r)) cases (104.6 vs. 90.7 min, p < 0.02), while EBL was equivalent (32.1 vs. 34.3 mL, p = 0.56). There was one post-operative hemorrhage requiring laparoscopic clot evacuation in the SPIDER((r)) cohort, and one wound infection in the LSG cohort. CONCLUSIONS: SPIDER((r)) sleeve gastrectomy is not inferior to LSG with regard to decrease in BMI and %EWL at 6-months post-operatively. The higher %EWL observed in the SPIDER((r)) cohort is likely due to patient selection bias. This study demonstrates that the SPIDER((r)) technique is a viable alternative to LSG with similar weight-loss outcomes. PMID- 26275544 TI - Laparoscopic versus open surgery for complicated appendicitis in adults: a randomized controlled trial. AB - BACKGROUND: The aim of this study was to assess whether laparoscopic appendectomy (LA) for complicated appendicitis (CA) effectively reduces the incidence of postoperative complications and improves various measurements of postoperative recovery in adults compared with open appendectomy (OA). METHODS: This single center, randomized controlled trial was performed in the Nagoya Daini Red Cross Hospital. Patients diagnosed as having CA with peritonitis or abscess formation were eligible to participate and were randomly assigned to an LA group or an OA group. The primary study outcome was development of infectious complications, especially surgical site infection (SSI), within 30 days of surgery. RESULTS: Between October 2008 and August 2014, 81 patients were enrolled and randomly assigned with a 1:1 allocation ratio (42, LA; 39, OA). All were eligible for study of the primary endpoint. Groups were well balanced in terms of patient characteristics and preoperative levels of C-reactive protein. SSI occurred in 14 LA group patients (33.3 %) and in 10 OA group patients (25.6 %) (OR 1.450, 95 % CI 0.553-3.800; p = 0.476). Overall, the rate of postoperative complications, including incisional or organ/space SSI and stump leakage, did not differ significantly between groups. No significant differences between groups were found in hospital stay, duration of drainage, analgesic use, or parameters for postoperative recovery except days to walking. CONCLUSION: These results suggested that LA for CA is safe and feasible, while the distinguishing benefit of LA was not validated in this clinical trial. PMID- 26275546 TI - 30-Day readmission after bariatric surgery in a publicly funded regionalized center of excellence system. AB - BACKGROUND: Avoidable readmission after surgery is a major burden on healthcare resources and is common after major surgery. Bariatric surgery is one of the most common surgical procedures in North America, and there is a paucity of strategies to prevent readmission. Strategies for prevention must first identify actual risk factors before interventions can be designed. METHODS: Our objective was to evaluate the readmission rate, characteristics of readmitted patients, and factors associated with readmission. We performed a population-based cohort study that included all patients who received a Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) procedure in Ontario from April 2009 until March 2012 for the purposes of weight loss. Data were derived from the Canadian Institute for Health Information Discharge Abstract Database and Hospital Morbidity Database. RESULTS: Over 3 years, 5007 procedures (91.7 % RYGB, 8.1 % SG) were performed with an overall 30-day readmission rate of 6.1 %. Readmission stays of 72 h or less accounted for 83 % of the cohort. The most common reasons for readmission were: infectious complications (24.6 %), pain (16.4 %) nausea/vomiting (11.5 %), bleeding complications (11.5 %), obstruction (5.6 %). A complication during initial admission OR 2.07 (95 % CI 1.44-2.97; P value < 0.001) and a length of stay greater than 2 days OR 1.40 (95 % CI 1.07-1.84; P value = 0.013) were independent predictors of readmission within 30 days. CONCLUSION: The readmission rate after bariatric surgery in Ontario is similar to other major population based bariatric surgery programs. Complications on initial admission and prolonged length of stay were independent predictors of readmission. Considering a large proportion of the readmissions were short term, future research into potential measures to prevent these readmissions is essential. PMID- 26275545 TI - What is the evidence for the use of low-pressure pneumoperitoneum? A systematic review. AB - BACKGROUND: Laparoscopic surgery has several advantages when compared to open surgery, including faster postoperative recovery and lower pain scores. However, for laparoscopy, a pneumoperitoneum is required to create workspace between the abdominal wall and intraabdominal organs. Increased intraabdominal pressure may also have negative implications on cardiovascular, pulmonary, and intraabdominal organ functionings. To overcome these negative consequences, several trials have been performed comparing low- versus standard-pressure pneumoperitoneum. METHODS: A systematic review of all randomized controlled clinical trials and observational studies comparing low- versus standard-pressure pneumoperitoneum. RESULTS AND CONCLUSIONS: Quality assessment showed that the overall quality of evidence was moderate to low. Postoperative pain scores were reduced by the use of low-pressure pneumoperitoneum. With appropriate perioperative measures, the use of low-pressure pneumoperitoneum does not seem to have clinical advantages as compared to standard pressure on cardiac and pulmonary function. Although there are indications that low-pressure pneumoperitoneum is associated with less liver and kidney injury when compared to standard-pressure pneumoperitoneum, this does not seem to have clinical implications for healthy individuals. The influence of low-pressure pneumoperitoneum on adhesion formation, anastomosis healing, tumor metastasis, intraocular and intracerebral pressure, and thromboembolic complications remains uncertain, as no human clinical trials have been performed. The influence of pressure on surgical conditions and safety has not been established to date. In conclusion, the most important benefit of low-pressure pneumoperitoneum is lower postoperative pain scores, supported by a moderate quality of evidence. However, the quality of surgical conditions and safety of the use of low-pressure pneumoperitoneum need to be established, as are the values and preferences of physicians and patients regarding the potential benefits and risks. Therefore, the recommendation to use low-pressure pneumoperitoneum during laparoscopy is weak, and more studies are required. PMID- 26275547 TI - Has endoscopic (TEP, TAPP) or open inguinal hernia repair a higher risk of bleeding in patients with coagulopathy or antithrombotic therapy? Data from the Herniamed Registry. AB - INTRODUCTION: Inguinal hernia operations in the presence of antithrombotic therapy, based on antiplatelet or anticoagulant drugs, or existing coagulopathy are associated with a markedly higher risk for onset of postoperative secondary bleeding. To date, there is a paucity of concrete data on this important clinical aspect of inguinal hernia surgery. Up till now, the endoscopic (TEP, TAPP) techniques have been considered to be more risky because of the extensive dissection involved. PATIENTS AND METHODS: Out of the 82,911 patients featured in the Herniamed Hernia Registry who had undergone inguinal hernia repair, 9115 (11 %) were operated on while receiving antithrombotic therapy or with existing coagulopathy. The implications of that risk profile for onset of postoperative bleeding were investigated in multivariable analysis. In addition, other influence variables were identified. RESULTS: The rate of postoperative secondary bleeding, at 3.91 %, was significantly higher in the risk group with coagulopathy or receiving antithrombotic therapy than in the group without that risk profile at 1.12 % (p < 0.001). Multivariable analysis revealed other influence variables which, in addition to coagulopathy or antithrombotic therapy, had a relevant influence on the occurrence of postoperative bleeding. These were open operation, a higher age, a higher ASA score, recurrence, male gender and a large hernia defect. Patients receiving antithrombotic therapy or with existing coagulopathy who undergo inguinal hernia operation have a fourfold higher risk for onset of postoperative secondary bleeding. Despite the extensive dissection required for endoscopic (TEP, TAPP) inguinal hernia repair, the risk of bleeding complications and complication-related reoperation appears to be lower. PMID- 26275548 TI - Financial modeling of current surgical robotic system in outpatient laparoscopic cholecystectomy: how should we think about the expense? AB - INTRODUCTION: More than 500,000 robotically assisted procedures were performed worldwide in 2013. Despite broad adoption, there remains a lack of clarity concerning the added cost of the robotic system to the procedure especially in light of an increasing number of ambulatory procedures which are now marketed by hospitals, surgeons and the manufacturer. These procedures are associated with much less reimbursement than inpatient procedures. It is unclear whether these added expenses can be absorbed in these scenarios. Reports vary in opinion concerning the added net costs during robotically assisted laparoscopic hernia or cholecystectomy. METHODS: The worldwide revenues, procedures, and the installed base of robotic system data were reviewed and reanalyzed from the 2013 Intuitive Surgical Investors report. This provided an opportunity to look cost per case projections from the vantage point of actual revenue. RESULTS: This analysis was based on revenue of 2.27 billion US dollars in the three categories of capital acquisition, instrumentation and accessories, and service revenue. These revenues were then spread across 523,000 cases with varying assumptions. Without regard to expense offsets, the additional cost ranges from $2908 to $8675 depending on what system was purchased and the ability to distribute costs against case volume. Estimates of commercial and government revenue were then compared against these expenses. CONCLUSION: The use of the extraordinary technology in the face of low morbidity low-cost established minimally invasive procedures needs to withstand scrutiny of outcome assessment, revenue and expense considerations and appropriateness review in order to create financially viable approaches to high volume minimally invasive procedures. Revenue estimates associated with outpatient reimbursement make it difficult to support these expenses, recognizing inpatient procedures represent a different net financial picture. PMID- 26275549 TI - Pilot study of a novel pain management strategy: evaluating the impact on patient outcomes. AB - BACKGROUND: Our objective was to evaluate the impact of a novel multimodal pain management strategy on intraoperative opioid requirements, postoperative pain, narcotic use, and length of stay. METHODS: Consecutive patients undergoing elective laparoscopic colorectal resection were managed with an experimental protocol. The protocol uses a post-induction, pre-incision bilateral TAP block and local peritoneal infiltration at port sites with long-acting liposomal bupivacaine (20 mL long-acting liposomal bupivacaine, 30 mL 0.25 % bupivacaine, 30 mL saline). Experimental patients were matched on age, body mass index, gender, comorbidity, diagnosis, and procedure to a control group that received no block or local wound infiltration. Both groups followed a standardized enhanced recovery pathway. Demographics, perioperative, and postoperative outcomes were evaluated. The main outcome measures were intraoperative opioids, postoperative pain, opioid use, and length of stay. RESULTS: Fifty patients were analyzed-25 experimental and 25 controls. Patients were well matched on all demographics. In both cohorts, the main diagnosis was colorectal cancer and primary procedure performed a segmental resection. Operative times were similar (p = 0.41). Experimental patients received significantly less intraoperative fentanyl (mean 158 mcg experimental vs. 299 mcg control; p < 0.01). The experimental group had significantly lower initial (p < 0.01) and final PACU pain scores (p = 0.04) and shorter LOS (3.0 vs. 4.1 days, p = 0.04) compared to controls. Experimental patients trended toward shorter PACU times and lower opioid use and daily pain scores throughout the hospital stay. Postoperative complication and readmission rates were similar across groups. There were no reoperations or mortality. CONCLUSIONS: Our multimodal pain management strategy reduced intraoperative opioid administration. Postoperatively, improvements in PACU time, postoperative pain and narcotic use, and lengths of stay were seen in the experimental cohort. With the favorable finding from the pilot study, further investigation is warranted to fully evaluate the impact of this pain management protocol on patient satisfaction, clinical and financial outcomes. PMID- 26275550 TI - Real-time fluorescence angiography by intra-arterial indocyanine green injection to identify obscure gastrointestinal bleeding territory: proof of concept in the porcine model. AB - BACKGROUND: Despite intensive preoperative localization workouts, intraoperative localization of the bleeding source in case of obscure gastrointestinal bleeding (OGIB) can be cumbersome and time-consuming. Our aim was to assess the feasibility of image-guided laparoscopic identification of the small bowel loop containing the bleeding source with and without near-infrared angiographic enhancement. MATERIALS AND METHODS: Angiography of superior mesenteric artery (SMA) branches was performed in 11 pigs using a right femoral artery approach, followed by a three-port laparoscopy, using a near-infrared-equipped laparoscope. Two pigs were used to identify the optimal intra-arterial indocyanine green (ICG) dose. Eight pigs were divided into two groups: ICG near-infrared angiography assisted laparoscopy (n = 4) and fluoroscopic-assisted laparoscopy (n = 4). Finally, in one pig, a novel OGIB model was created and used to evaluate the ICG enhancement pattern in the presence of active bleeding. RESULTS: Mean time to identify the fluorescence signal from the small bowel segment fed by the catheterized SMA branch was 13.75 +/- 7.8 s, which was statistically significantly shorter than the time required to identify the tip of the catheter by fluoroscopic guidance, i.e., 243.25 +/- 107 s (p = 0.02). CONCLUSIONS: Near infrared fluorescence angiography using intra-arterial ICG injection provides a fast image-guided intraoperative localization of the small bowel loop fed by the arterial territory identified as bleeding by digital subtraction angiography and could help target the bleeding source during OGIB surgery. PMID- 26275551 TI - Feasibility and safety of laparoendoscopic single-site surgery of total extraperitoneal inguinal hernia repair after previous open groin hernia repair: a comparative study. AB - BACKGROUND: This study is aimed at evaluating the feasibility and safety of laparoendoscopic single-site surgery (LESS) for totally extraperitoneal (TEP) endoscopic hernia surgery after previous open groin hernia repair that may hamper preperitoneal dissection. METHODS: This prospective cohort study included 213 consecutive patients undergoing LESS TEP hernia repair between January 2009 and December 2013. The study group consisted of 36 patients with a history of previous open inguinal hernia repair before undergoing LESS TEP hernia repair. The study enrolled the other 177 patients who underwent LESS TEP during the same period and were enrolled as the control group. We obtained perioperative data for all patients including demographic data, operation time, length of hospital stay, narcotic dose, conversions, and complications. RESULTS: A total of 213 patients with inguinal hernia underwent LESS TEP repair. One case in the control group (0.56 %) required conversion to LESS transabdominal preperitoneal hernia repair, while no cases in the study group required conversion. We observed no differences between the two groups in terms of operative time, analgesic use, hospital stay, and postoperative complications. CONCLUSIONS: LESS TEP hernia repair for patients with previous open inguinal hernia repair can be performed safely by experienced surgeons. Operative outcomes were comparable between both the primary inguinal and recurrent hernia groups. PMID- 26275552 TI - Endoscopic suturing versus endoscopic clip closure of the mucosotomy during a per oral endoscopic myotomy (POEM): a case-control study. AB - INTRODUCTION: Obtaining an adequate mucosal closure is one of the crucial steps in per-oral endoscopic myotomy (POEM). Thus far, there have been no objective data comparing the various available closure techniques. This case-controlled study attempts to compare the application of endoscopic clips versus endoscopic suturing for mucosotomy closure during POEM cases. METHODS: A retrospective review of our prospective POEM database was performed. All cases in which endoscopic suturing was used to close the mucosotomy were matched to cases in which standard endoclips were used. Overall complication rate, closure time and mucosal closure costs between the two groups were compared. RESULTS: Both techniques offer good clinical results with good mucosal closure and the absence of postoperative leak. Closure time was significantly shorter (p = 0.044) with endoscopic clips (16 +/- 12 min) when compared to endoscopic suturing (33 +/- 11 min). Overall, the total closure cost analysis showed a trend toward lower cost with clips (1502 +/- 849 USD) versus endoscopic suturing (2521 +/- 575 USD) without reaching statistical significance (p = 0.073). CONCLUSION: The use of endoscopic suturing seems to be a safe method for mucosal closure in POEM cases. Closure time is longer with suturing than conventional closure with clips, and there is a trend toward higher overall cost. Endoscopic suturing is likely most cost-effective for difficult cases where conventional closure methods fail. PMID- 26275553 TI - Surgical management of super-super obese patients: Roux-en-Y gastric bypass versus sleeve gastrectomy. AB - INTRODUCTION: Among morbidly obese adult patients (BMI >40 kg/m(2)), those who are super-super obese (BMI >60 kg/m(2)) present particular challenges for bariatric surgeons. Surgical management of super-super obese (SSO) patients has been associated with higher morbidity and mortality and increased surgical risk. The optimal surgical management of these patients is controversial. The aim of this study was to compare perioperative outcomes, percent excess weight loss (%EWL), and percent weight loss (%WL) in super-super obese patients who underwent either SG or RYGB. MATERIALS AND METHODS: This study was a nonrandomized, controlled, retrospective review of 89 SSO patients who underwent SG or RYGB at the University of Illinois Hospital and Health Sciences System from January 2008 to June 2014. Patient demographics, pre-surgical comorbidities, perioperative parameters, post-operative complications (leak, conversion to open surgery, and 30-day mortality), and post-operative outcome months were examined. RESULTS: Seventy-seven patients underwent SG (nine robotic sleeve and 68 laparoscopic sleeve gastrectomy), and 12 underwent RYGB. The mean pre-operative BMI was 63.4 kg/m(2) (SD = 3.7 kg/m(2)). The mean operative time was 88.4 min (SD = 31.7) for the SG patients and 219.2 min (SD = 80.2) for the RYGB patients. There were no significant differences in complications or length of hospitalization between the groups. There were significant differences in %EWL and %WL at 12- and 24-month follow-up between groups (p's < 0.05). CONCLUSIONS: Based on the results from this sample of patients, SG and RYGB appear to be viable procedures for the surgical management of super-super obese patients. RYGB, however, provides a significantly higher %EWL and %WL at 12 and 24 months compared to SG, which in turn, yields acceptable but lower %EWL and %WL. PMID- 26275554 TI - Laparoscopic simultaneous resection of colorectal primary tumor and liver metastases: a propensity score matching analysis. AB - BACKGROUND: Preliminary series have shown the feasibility of combined laparoscopic resection of colorectal cancer (CRC) and synchronous colorectal liver metastases (SCRLM). The aim of this study was to compare the short- and long-term outcomes for matched patients undergoing combined resections. METHODS: An international multicenter database of 142 patients that underwent combined laparoscopic resection of CRC and SCRLM between 1997 and 2013 was compared to a database of 241 patients treated by open during the same period. Comparison of short- and long-term outcomes was performed after propensity score adjustment. RESULTS: After matching, 89 patients were compared in each group including mostly ASA I-II patients, presenting with mean number of 1.5 CRLM, with a mean diameter of 30 mm, and resectable by a wedge resection or a left lateral sectionectomy. A rectal resection was required in 46 and 43 % of laparoscopic and open procedures, respectively (p = 0.65). There was no difference in global operative time, blood loss and transfusion rates between the two groups. A conversion was required in 7 % of the laparoscopic procedures. Morbidity rates were similar in the two groups (p = 1.0). The 3-year overall survival in the laparoscopy and open groups were 78 and 65 %, respectively (p = 0.17). CONCLUSIONS: In patients without severe comorbidities presenting with one, small (<=3 cm), CRLM resectable by a wedge resection or a left lateral sectionectomy, combined laparoscopic resection of CRC and SCRLM allowed similar short- and long-term outcomes compared with the open approach. PMID- 26275555 TI - Long-term outcome of laparoscopic ablation therapies for unresectable hepatocellular carcinoma: a single European center experience of 426 patients. AB - BACKGROUND: Radiofrequency ablation (RFA) is widely used as a first-line option in patients with hepatocellular carcinoma (HCC). However, since percutaneous approach of RFA may be, in some cases, unfeasible by the tumor size and its location, laparoscopic ablation therapies (LATs) were used as an alternative. Objective of the present study was to assess the efficacy of laparoscopic ultrasound examination in addition to LATs in the treatment of HCC in patients not eligible for percutaneous RFA or surgical resection. METHODS: Four hundred and twenty-six patients who underwent LATs were analyzed. Laparoscopic approach was offered to patients fulfilling at least one of the following criteria: (a) patients with a single nodule or up to three nodules smaller than 3 cm not suitable for liver transplantation or not eligible for HR because of severe portal hypertension, impaired liver function, or coexistent comorbidities; (b) patients not suitable for percutaneous RFA because of inconvenient tumor location; and (c) short-term recurrence of HCC (<3 months). RESULTS: Technical success was achieved in one session in 396 patients (93 %). One-month mortality and morbidity rates were 0.23 % (1 patient) and 25 % (106 patients), respectively. During a median follow-up of 37.2 months (range 2-193) in the remaining 425 patients, 276 (65 %) developed intra-hepatic recurrence: It appeared as a local tumor progression in 65 cases (15 %). Patients median survival was 39 months (95 % CI 34.8-47.2), while overall survivals at 1, 3, and 5 years were 88, 55, and 34 %, respectively. CONCLUSIONS: In the treatment of HCC, LATs proved to be a safe and effective technique, as they permit to treat with low-morbidity-rate lesions not manageable by percutaneous approach. Moreover, they allow achieving a more accurate staging of the disease in one fifth of patients, thus better redefining the prognosis of such individuals. PMID- 26275556 TI - Major bile duct injury requiring operative reconstruction after laparoscopic cholecystectomy: a follow-on study. AB - BACKGROUND: Bile duct injury (BDI) after laparoscopic cholecystectomy (LC) has significant cost impact and is a significant source of morbidity and mortality. We undertook a population-based assessment of the national experience with BDI between 2001 and 2011 and compared this to our report for the prior decade. METHODS: Using the nationwide inpatient sample (NIS) for 2001-2011, we identified patients who underwent LC or partial cholecystectomy, with and without biliary reconstruction. Data were analyzed using methods that accounted for the hierarchical, stratified random sampling of the NIS. Both univariate modeling and multivariate modeling were performed. RESULTS: LCs increased from 71.1 % in 2001 to 79.0 % in 2011 (p < 0.0001). Annual mortality decreased from 0.56 to 0.38 % (p = 0.002). In 2001, 0.11 % of LCs were associated with biliary reconstruction versus 0.09 % in 2011 (p = 0.15) with rates ranging from 0.08 to 0.12 %. The need for reconstruction was associated with an average in-hospital mortality rate of 4.4 %. Mortality rates from LC remained consistent across the study period (average mortality, 0.10 %, p = 0.57). Under multivariate analysis, admission to rural or urban non-teaching centers was associated with a decreased rate of injury; the majority of major BDIs were admitted from clinic or outpatient settings. These results are consistent with results from the prior decade. Neither emergent admission nor race was associated with increased odds of BDI, and this differs from our prior analysis. CONCLUSION: LC continued to increase in utilization between 2001 and 2011. Although rates of BDI have decreased, the need for reconstruction continues to be associated with a significant mortality. In addition, mortality related to biliary reconstruction is also higher than previously published series and may reflect the complexity of managing biliary injury as well as the higher likelihood of these patients having comorbid conditions. PMID- 26275558 TI - Enzymes of anaerobic ethylbenzene and p-ethylphenol catabolism in 'Aromatoleum aromaticum': differentiation and differential induction. AB - The denitrifying bacterium 'Aromatoleum aromaticum' strain EbN1 is one of the best characterized bacteria regarding anaerobic ethylbenzene degradation. EbN1 also degrades various other aromatic and phenolic compounds in the absence of oxygen, one of them being p-ethylphenol. Despite having similar chemical structures, ethylbenzene and p-ethylphenol have been proposed to be metabolized by completely separate pathways. In this study, we established and applied biochemical and molecular biological methods to show the (almost) exclusive presence and specificity of enzymes involved in the respective degradation pathways by recording enzyme activities, complemented by heme staining, immuno- and biotin-blotting analyses. These combined results substantiated the predicted p-ethylphenol degradation pathway. The identified enzymes include a heme c containing p-ethylphenol-hydroxylase, both an (R)- and an (S)-specific alcohol dehydrogenase as well as a novel biotin-dependent carboxylase. We also establish an activity assay for benzoylacetate-CoA ligases likely being involved in both metabolic pathways. PMID- 26275559 TI - Synthesis, Characterization, Fluorescence, Photocatalytic and Antibacterial Activity of CdS Nanoparticles Using Schiff Base. AB - Cadmium sulfide nanoparticles (CdS NPs) were successfully prepared using sonochemical method by employing Schiff-base, (2-[(4-methoxy-phenylimino)-methyl] 4-nitro phenol) as a complexing agent. Here, SB is used as a ligand to control the morphology of NPs. XRD patterns and TEM images show that the synthesized CdS NPs have cubic structures with a diameter of about 2-10 nm. The formation of CdS NPs and their optical, structure, thermal and morphologies were studied by means of UV-vis DRS, fluorescence, FTIR, zeta potential, XRD, SEM and TEM. The interactions between CdS NPs and SB were investigated in an aqueous solution using fluorescence spectroscopy. The fluorescence quenching studies suggest that SB quenches the fluorescence of CdS NPs effectively. The degradation kinetics of methyl red (MR) by the photocatalyst was followed by Langmuir-Hinshelwood model. The results revealed that photocatalytic degradation of MR by SB capped CdS NPs could be considered as a practical and reliable technique for the removal of environmental pollutants. The antibacterial activity of samples was evaluated against E. coli, S. aureus and P. aeruginosa and the results were compared. SB and SB capped CdS NPs could be a potential antibacterial compounds after further investigation. PMID- 26275557 TI - Factors affecting the achievement of Japanese-style deep knee flexion after total knee arthroplasty using posterior-stabilized prosthesis with high-flex knee design. AB - BACKGROUND: Achievement of very deep knee flexion after total knee arthroplasty (TKA) can play a critical role in the satisfaction of patients who demand a floor sitting lifestyle and engage in high-flexion daily activities (e.g., seiza sitting). Seiza-sitting is characterized by the knees flexed >145o and feet turned sole upwards underneath the buttocks with the tibia internally rotated. The present study investigated factors affecting the achievement of seiza-sitting after TKA using posterior-stabilized total knee prosthesis with high-flex knee design. METHODS: Subjects comprised 32 patients who underwent TKA with high-flex knee prosthesis and achieved seiza-sitting (knee flexion >145o) postoperatively. Another 32 patients served as controls who were capable of knee flexion >145o preoperatively, but failed to achieve seiza-sitting postoperatively. Accuracy of femoral and tibial component positions was assessed in terms of deviation from the ideal position using a two-dimensional to three-dimensional matching technique. Accuracies of the component position, posterior condylar offset ratio and intraoperative gap length were compared between the two groups. RESULTS: The proportion of patients with >3o internally rotated tibial component was significantly higher in patients who failed at seiza-sitting (41 %) than among patients who achieved it (13 %, p = 0.021). Comparison of intraoperative gap length between patient groups revealed that gap length at 135o flexion was significantly larger in patients who achieved seiza-sitting (4.2 +/- 0.4 mm) than in patients who failed at it (2.7 +/- 0.4 mm, p = 0.007). Conversely, no significant differences in gap inclination were seen between the groups. CONCLUSIONS: From the perspective of surgical factors, accurate implant positioning, particularly rotational alignment of the tibial component, and maintenance of a sufficient joint gap at 135o flexion appear to represent critical factors for achieving >145o of deep knee flexion after TKA. PMID- 26275560 TI - Hepatitis B: Working Towards a Cure. AB - First-line oral therapies for hepatitis B are effective at viral suppression, and treatment can lead to biochemical improvement and histologic regression. Unfortunately, recommended endpoints of treatment such as HBeAg loss and seroconversion may not be durable, with high rates of seroreversion, requiring monitoring, and unfortunately, low rates of HBsAg loss/seroconversion. Additionally, meeting these endpoints requires years or even indefinite administration, leading to concerns regarding cost, side effects, and high rates of nonadherence. This article will review defined endpoints of therapy and their durability, the risks of long-term therapy, and the evolving new therapies aimed at a viral cure. PMID- 26275561 TI - Erratum to: A Quantitative Analysis of Lip Aesthetics: The Influence of Gender and Aging. PMID- 26275562 TI - Retro-Areola Distally Based Flap in the Management of the Full Expression of Tuberous Breast: A Simple Strategy to Resolve a Weak Point of the Deformity. AB - BACKGROUND: Tuberous breast is a rare congenital deformity which is likely to appear in various clinical forms, the worst being characterized by severe hypoplasia. This clinical expression may represent one of the greatest challenges in breast surgery due to malformation memories that restrict the reshaping of the mammary cone that would not otherwise be solved through a simple breast augmentation. To improve the quality of the final results correction of the tuberous aspect often requires the use of adipo-glandular flaps frequently described in the literature to reconstruct the inferior mammary pole which works efficiently, even though a typical depression often remains between the inferior border of the areola and the closer skin to recall the memory of the tuberous aspect. METHODS: Between September 2006 and March 2014, 71 patients with tuberous breasts underwent surgical procedures to repair the deformities. The mean patient age was 18.6 years (ranging between 17 and 23). A periareolar approach, adipo glandular flaps, and dual plane subpectoral breast implant placements were used in all the cases. All the procedures were performed in a single stage under local anesthesia plus sedation. RESULTS: Follow-up ranged from 6 months to 6 years. CONCLUSION: The authors propose the use of a retro-areola glandular flap to resolve the typical residual depression of the final mammary aspect thus to overcome the malformation completely. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . PMID- 26275563 TI - Vladimir M. Kernig (1840-1917). PMID- 26275564 TI - C9ORF72 intermediate repeat expansion in patients affected by atypical parkinsonian syndromes or Parkinson's disease complicated by psychosis or dementia in a Sardinian population. AB - The hexanucleotide repeat expansion GGGGCC in the C9ORF72 gene larger than 30 repeats has been identified as a major genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recent papers investigated the possible pathogenic role and associated clinical phenotypes of intermediate C9ORF72 repeat expansion ranging between 20 and 30 repeats. Some studies suggested its pathogenicity for typical Parkinson's disease (PD), atypical parkinsonian syndromes, FTD with/without parkinsonism, and ALS with/without parkinsonism or with/without dementia. In our study, we aimed to screen patients affected by atypical parkinsonian syndromes or PD complicated by psychosis or dementia for the presence of C9ORF72 repeat expansions, and in unrelated age- and sex-matched healthy controls. Consecutive unrelated patients with atypical parkinsonian syndromes and patients with PD complicated by psychosis or dementia were included in this study. Atypical parkinsonian syndromes were further divided into two groups: one with patients who met the criteria for the classic forms of atypical parkinsonism [multiple system atrophy (MSA), Lewy body disease (LBD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD)] ;and patients who did not meet the above criteria, named non-classical atypical parkinsonism with or without dementia. Ninety-two unrelated patients (48 men, 44 women) were enrolled. None of the patients was found to be carriers of C9ORF72 repeat expansions with more than 30 repeats. Intermediate 20-30 repeat expansions were detected in four female patients (4.3 %). Three of them presented clinical features of atypical parkinsonian syndromes, two with non-classical atypical parkinsonism and dementia FTD-like, and one with non-classical atypical parkinsonism without dementia. The other patient presented clinical features of typical PD complicated by psychosis. Among 121 control subjects, none presented long or short expansion for the C9ORF72 gene. Our findings seem to support the hypothesis that the hexanucleotide expansions of C9ORF72 gene with intermediate repetitions between 20 and 29 repetitions could be associated with typical PD with psychosis or dementia and atypical parkinsonisms with dementia (non classical atypical parkinsonism with dementia FTD-like) or without dementia (non classical atypical parkinsonism upper MND-like), although the causal relationship is still unclear. In these latter patients, parkinsonism, more or less levodopa responsive, constituted the symptomatological central core at onset. PMID- 26275565 TI - Influence of glycaemic control on the outcomes of patients treated by intravenous thrombolysis for cerebral ischaemia. AB - Whether the glycaemic control during the first hours of cerebral ischaemia treated by thrombolysis influences outcomes remains unsettled. We aimed at evaluating the quality of the glycaemic control and whether patients with well controlled glycaemia after thrombolysis for acute cerebral ischaemia have better outcomes. We retrospectively analysed data prospectively collected in consecutive stroke patients who received i.v. thrombolysis at the Lille University Hospital. Patients with glycaemia >1.6 g/l (8.9 mmol/l) at any point during the first 48 h received insulin. We used 2 definitions of well controlled glycaemia: (i) "well controlled 100 %" when 100 % glycaemia were <1.6 g/l (8.9 mmol/l), and (ii) "well controlled 70 %" when at least 70 % glycaemia were <1.6 g/l (8.9 mmol/l). The outcome measures at 3 months were (1) independence [modified Rankin scale (mRS) score 0 or 1], (2) absence of handicap (mRS 0-2), (3) death, and (4) symptomatic intracerebral haemorrhage (sICH). Of 875 consecutive patients, 657 (75.2 %) were considered as well controlled with a threshold at 100 % and 736 (84.2 %) with a threshold at 70 %. The glycaemic control was not independently associated with any of the four outcome measures. In patients treated by insulin, hypoglycaemic events were rare (2.1 % of all patients) and of moderate intensity [>0.5 g/l (2.8 mmol/l)]. The quality of the glycaemic control was not associated with outcomes in patients treated by thrombolysis. A possible explanation is that the glycaemic control after thrombolysis has minor influence compared with glycaemic control before thrombolysis when the artery is not yet re-open and the penumbra area at maximum. PMID- 26275567 TI - [Not Available]. AB - N-Ethyl-2-pyrrolidone (NEP), a polar aprotic solvent, is used in many applications as substitute for the structural analogue N-methyl-2-pyrrolidone (NMP), e. g. for surface coatings, in cleaning agents and paint strippers. Monitoring studies indicate that individuals within the general public, without occupational exposure, may be exposed to NEP to an extent, which is comparable to NMP. As NMP, NEP presents a potential health hazard due to its developmental toxicity and teratogenicity. Exposure to NEP can be quantified by the determination of the excretion of its urinary metabolites 5-Hydroxy-N-ethyl-2 pyrrolidone (5-HNEP) and 2-Hydroxy-N-ethylsuccinimide (2-HESI). For the derivation of HBM values, the german Human Biomonitoring Commission (HBM commission) evaluated different toxicological endpoints and finally decided on the BMDL05 and the BMD10 for the endpoint "reduced grasp intensity" of a subchronic feeding study with rats as point of departure (POD) for further procedural steps. The resulting HBM-I and HBM-II values for the sum of the metabolites 5-HNEP and 2-HESI in the urine of children are 10 resp. 25 mg/l and in the urine of adults are 15 resp. 40 mg/l. If the HBM values are exceeded, a check-up will be necessary at first. Measurements above the HBM-II value give cause for concern, especially for pregnant women. Air measurements to determine the source of exposure can be useful. The possibility of skin absorption from use of cleaning agents and paint strippers should also be traced. As NEP und NMP have similar toxic effects, a potential mixed exposure to both substances has to be taken into account. PMID- 26275568 TI - [Not Available]. PMID- 26275569 TI - [Not Available]. PMID- 26275570 TI - [Regional and nationwide developments in telemedicine. A contradiction?]. AB - Numerous telemedical projects have not been managed to widen itself. The federal states have sponsored many projects in the past. The central question therefore is, if projects can be spread everywhere. To answer this question, at first the initiatives of the federal states are introduced very briefly. Important aspects are then defined for a nationwide behaviour. Important aspects are then defined. ln the result it turns out that the federal states play an indispensable role for telemedicine. PMID- 26275571 TI - [Not Available]. PMID- 26275566 TI - Influence of previous physical activity on the outcome of patients treated by thrombolytic therapy for stroke. AB - Physical activity prevents stroke and is associated with less severe strokes. The neuroprotective effect in patients treated with intravenous (i.v.) recombinant tissue plasminogen activator (rt-PA), remains uncertain. We aimed at evaluating the relationship between previous physical activity and outcomes in stroke patients treated with i.v. rt-PA. OPHELIE-SPORT was a prospective observational multicenter study conducted in French and Japanese stroke patients treated with i.v. rt-PA. We evaluated the presence, weekly duration (<2, 2-5, >5 h) and intensity (light, moderate, heavy) of previous leisure-time physical activity according to standardized criteria. The primary end-point was an excellent outcome [modified Rankin Scale (mRS) 0-1 or similar to the pre-stroke mRS] after 3 months. Secondary end-points were good outcome (mRS 0-2 or similar to the pre stroke mRS), and death. Of 519 patients, 74 (14.3 %) had regular physical activity before stroke. They were 14 years younger (p < 0.001), treated 25 min earlier (p = 0.004) and more likely to be men, free of pre-stroke handicap (mRS = 0), atrial fibrillation, arterial hypertension, and diabetes mellitus. National Institutes of Health Stroke Scale scores, at baseline (p = 0.183) and 24 h later (p = 0.203), did not differ between patients with and without physical activity. After adjustment on confounders, there was no association between previous leisure-time physical activity and outcome. Outcomes 3 months after treatment of cerebral ischaemia with i.v. rt-PA are not influenced by previous physical activity. PMID- 26275573 TI - Molecular Simulations of Fatty-Acid Methyl Esters and Representative Biodiesel Mixtures. AB - Despite the importance of fatty-acid methyl esters (FAMEs) as key components of various green solvents, detergents, plasticizers, and biodiesels, our understanding of these systems at the molecular level is limited. An enhanced molecular-level perspective of FAMEs will enable a detailed analysis of the polymorph and crystallization phenomena that adversely impact flow properties at low temperatures. Presented here, is the parameterization and validation of a charge-modified generalized amber force field (GAFF) for eight common FAMEs and two representative biodiesel mixtures. Our simulations accurately reproduce available experimental data (e.g. densities and self-diffusivity coefficients) and their trends, with respect to temperature and degree of unsaturation. Structural analyses from our simulations provide a more detailed picture of liquid-phase molecular ordering in FAMEs and confirm recent experimental hypotheses. This study provides a firm foundation to initiate further studies into the mechanisms that drive crystallization phenomena at the molecular level. PMID- 26275574 TI - Cefuroxime-induced cutaneous pustular leukocytoclastic vasculitis with Koebner phenomenon on the donor area of a skin graft. PMID- 26275572 TI - A window-of-opportunity biomarker study of etodolac in resectable breast cancer. AB - Observational data show that nonsteroidal anti-inflammatory drug (NSAID) use is associated with a lower rate of breast cancer. We evaluated the effect of etodolac, an FDA-approved NSAID reported to inhibit cyclooxygenase (COX) enzymes and the retinoid X receptor alpha (RXR), on rationally identified potential biomarkers in breast cancer. Patients with resectable breast cancer planned for initial management with surgical resection were enrolled and took 400 mg of etodolac twice daily prior to surgery. Protein and gene expression levels for genes related to COX-2 and RXRalpha were evaluated in tumor samples from before and after etodolac exposure. Thirty subjects received etodolac and 17 subjects were assayed as contemporaneous or opportunistic controls. After etodolac exposure mean cyclin D1 protein levels, assayed by immunohistochemistry, decreased (P = 0.03). Notably, pre- versus post cyclin D1 gene expression change went from positive to negative with greater duration of etodolac exposure (r = 0.64, P = 0.01). Additionally, etodolac exposure was associated with a significant increase in COX-2 gene expression levels (fold change: 3.25 [95% CI: 1.9, 5.55]) and a trend toward increased beta-catenin expression (fold change: 2.03 [95% CI: 0.93, 4.47]). In resectable breast cancer relatively brief exposure to the NSAID etodolac was associated with reduced cyclin D1 protein levels. Effect was also observed on cyclin D1 gene expression with decreasing levels with longer durations of drug exposure. Increased COX-2 gene expression was seen, possibly due to compensatory feedback. These data highlight the utility of even small clinical trials with access to biospecimens for pharmacodynamic studies. PMID- 26275576 TI - Cardiac sympathetic dysfunction in anti-NMDA receptor encephalitis. AB - Patients with anti-NMDA receptor (anti-NMDAR) encephalitis frequently suffer from autonomic dysfunctions, which can cause substantial morbidity. This study assessed cardiac autonomic functions in patients with anti-NMDAR encephalitis using heart rate variability (HRV) analysis. This was a retrospective single center case-control study. Eleven patients with anti-NMDAR encephalitis and 15 age- and sex-matched controls were included in this study. To ensure that autonomic dysfunction does not occur in any encephalitis, we additionally analyzed HRV of 9 patients with herpes encephalitis (HSE) and compared with that of NMDAR encephalitis patients and controls. Five minute resting stationary electrocardiogram was collected from each subject, and HRV was analyzed. Total power and low frequency (LF) power were lower in anti-NMDAR encephalitis patients than those in controls (p=0.005, 0.001 respectively), indicating cardiac autonomic dysfunction especially in sympathetic system. Patients with HSE showed no significant difference in HRV parameters compared with that of controls. Cardiac autonomic dysfunction was associated with 3 month functional outcome in anti-NMDAR encephalitis patients. PMID- 26275577 TI - Molecular cloning and functional characterization of feline MAVS. AB - The mitochondrial anti-viral signaling protein (MAVS) plays an important role in the type I IFN response. In this study, two feline MAVS transcripts were cloned. Both transcripts have the same open reading frame encoding 523 amino acids. The putative protein shares 76.6 % similarity with canine and exhibits similarity to human, mouse, rat, bovine and porcine, ranging from 46.1 to 65.8 %. Deletion mutant analysis indicated that the transmembrane (TM) domain is necessary for localization in the mitochondrial membrane, and both the caspase activation and recruitment domain and TM domain are indispensible for activating the IFN-beta response. Additionally, Sendai virus-induced IFN-beta promoter activation was significantly inhibited by siRNA targeting MAVS. Finally, miniMAVS, a second protein encoded by MAVS mRNA, was identified, which interfered with the IFN-beta response via the inhibition of NF-kappaB activation. The identification of MAVS will promote the understanding and control of feline infectious diseases. PMID- 26275578 TI - Assessment and delivery of treatment for hepatitis C virus infection in an opioid substitution treatment clinic with integrated peer-based support in Newcastle, Australia. AB - BACKGROUND: Among people who inject drugs (PWID), the prevalence of hepatitis C virus (HCV) infection is high; however HCV treatment uptake remains low. New models of care are needed to address the growing burden of HCV-related disease in PWID and to understand the barriers to assessment and treatment of HCV. This study evaluated assessment and treatment for HCV infection among PWID attending an opioid substitution treatment (OST) clinic with an integrated peer support worker model. METHODS: Clients with a history of IDU and chronic HCV infection, attending the Newcastle Pharmacotherapy Service, Newcastle Australia, were recruited as part of a multisite prospective observational study (the ETHOS Cohort). Additional chart review was conducted for clients not enrolled in the ETHOS Cohort. A peer support worker was introduced to complement and extend services offered by the clinical team. Client contacts and assessments with a nurse and/or peer worker were evaluated, including those who commenced HCV treatment. RESULTS: A total of 1447 clients attended the OST service during February 2009 and June 2014. Of these, 378 (26%) were assessed by a nurse and 242 (17%) by a clinician. HCV treatment was commenced by 20 (5%) participants and 15 (75%) achieved a sustained virological response (SVR). During May 2009 and July 2011, 332 nurse contacts and 726 peer worker contacts were evaluated. The nurse led contacts were related to HCV treatment (50%) and review of pathology tests (34%), whereas peer worker contacts included discussion about HCV treatment (75%), education, counselling and/or support (53%) and general discussion about HCV infection (59%). CONCLUSION: These data demonstrate that peer support workers facilitate broader discussion about HCV treatment, education and/or support, allowing nurses to focus on HCV-related assessment and treatment. HCV treatment uptake was very low in this cohort, but SVR was high. The integration of peer support workers in treatment programs within OST clinics may address barriers to HCV care, but further studies are needed to assess their impact on assessment and treatment outcomes. PMID- 26275579 TI - Minimally invasive medial patellofemoral ligament reconstruction for patellar instability using an artificial ligament: A two year follow-up. AB - BACKGROUND: Recurrence of acute patellar dislocation affects approximately 30% of individuals, and up to 75% of those with grade IV instability. The medial patellofemoral ligament (MPFL) is considered to be critical for patellar stabilization. MPFL reconstruction with allografts has been proposed to reduce risk of recurrence, but there is limited evidence about the safety and effectiveness of techniques using synthetic allografts. METHODS: We present a retrospective case series of 29 individuals who underwent a MPFL reconstruction between 2009 and 2012, using an artificial ligament for patellar instability by a single surgeon. Clinical, radiological and functional outcomes were measured at a minimum of 24 months. RESULTS: 31 knees (29 individuals) were followed up for a median of 43 (range: 24-68) months. Using the Crosby and Insall grading system, 21 (68%) were graded as excellent, nine (29%) were good, one (3%) as fair and none as worse at 24 months. The mean improvement in Lysholm knee score for knee instability was 68 points (standard deviation 10). Ligamentous laxity was seen in 17 (55%) of individuals. In this subset, 12 were graded as excellent, four as good and one as fair. The mean improvement in patellar height was 11% at three months follow-up. All knees had a stable graft fixation with one re-dislocation following trauma. CONCLUSIONS: We propose a minimally invasive technique to reconstruct the MPFL using an artificial ligament allowing early mobilization without bracing. This study indicates the procedure is safe, with a low risk of re-dislocation in all grades of instability. LEVEL OF EVIDENCE: Level IV Case Series. PMID- 26275580 TI - Determinants of Resource Utilization in a Tertiary Pediatric and Congenital Echocardiographic Laboratory. AB - We sought to determine the relation between technical charges for transthoracic echocardiograms (TTE) and total time for study completion (TT), identify factors associated with high TT, and create a scoring system to predict high TT studies. We analyzed a quality improvement database that prospectively tracked patient flow through TTEs in our laboratory for 3 consecutive months. The performing sonographer or fellow recorded TT and its components for every study. Patient and scan characteristics were abstracted from the clinical database and technical charges from the financial database. Factors independently associated with high TT (top quartile >=85 minutes) were identified in 1,686 studies and validated in the remaining 847 studies. Median age was 7.8 years (0 to 77.9) and median TT was 65 minutes (14 to 370 minutes). Charges correlated poorly with TT (r = 0.2). Multivariate analysis identified several independent factors associated with high TT. The final model had an area under the curve of 0.78 in the development sample and 0.75 in the validation sample. On the basis of the final model, we developed a risk score for TT >=85 minutes. The prevalence of high TT was 15% in low-score studies, 51% in medium-score studies, and 81% in high-score studies. In conclusion, this is the first study to demonstrate poor correlation between technical charges for pediatric/congenital echocardiography and TT, identify risk factors for high TT, and develop a high TT risk scoring system. These data may assist in resource allocation for pediatric/congenital echocardiograms and inform reimbursement systems. PMID- 26275583 TI - Intranasal insulin influences the olfactory performance of patients with smell loss, dependent on the body mass index: A pilot study. AB - BACKGROUND: The application of intranasal insulin in healthy humans has been linked to improved memory function, reduced food intake, and increased olfactory thresholds. There has also been some correlation between the morbidities associated with central nervous system (CNS) insulin resistance, such as type II diabetes mellitus, Alzheimer's disease, obesity, and impaired odour recognition. Given that impaired odour recognition is an important component of olfactory performance, mechanisms that govern these effects may account for impaired olfactory functions in anosmic patients. METHODOLOGY: Ten patients with post infectious olfactory loss received intranasal administration of 40 IU insulin or a placebo solution, as well as olfactory performance tests before and after administration. RESULTS: When administered insulin, patients exhibited an immediate performance improvement with regard to olfactory sensitivity and olfactory intensity ratings. In addition, more odours were correctly identified. Furthermore, an improvement in the odour identification task was detected in patients with higher body mass index. CONCLUSION: Results of this pilot study shed light on the link between cerebral insulin level and an impaired sense of smell. This research line might provide a better understanding of olfactory loss in relation to eating and dietary behavior, and could offer opportunities to develop faster therapeutic intervention for patients with olfactory dysfunction. PMID- 26275581 TI - Assessment of Local Dose Reference Values for Recanalization of Chronic Total Occlusions and Other Occlusions in a High-Volume Catheterization Center. AB - The increasing number and complexity of these procedures have led to a higher number of patients at risk for tissue reactions like skin injuries. Monitoring of their dose indicators is essential in recognizing these patients. The aim of this work was to determine local diagnostic reference levels (DRLs) for recanalization of chronic total occlusion (CTO) and other occlusions procedures. All data from patients who underwent cardiac procedures were reviewed and classified according to their complexity. Dose indicators such as fluoroscopy time (FT), dose area product (DAP), and air kerma at patient entrance reference point (AKr) were recorded. Correlations with patient's body mass index, operators, procedure strategy, and complexity were studied. For CTO, the mean DAP, AKr, and FT were 252 +/- 234 Gycm(2), 3,985 +/- 3,579 mGy, and 47 +/- 36 minutes, respectively. To better reflect the non-Gaussian distribution of data, the median and the 75th percentile values were also reported: median DAP, 172 Gycm(2); 75th percentile DAP, 350 Gycm(2); median AKr, 2,714 mGy; and 75th percentile AKr, 5,921 mGy. A tentative new set of values were suggested to take into account the complexity difference in recanalization of total occlusions according to their antegrade or retrograde approach. These approach-specific DRLs for total occlusions were mean DAP (120 +/- 114 Gycm(2)), mean AKr (1,789 +/- 1,933 mGy), and mean FT (22 +/- 18 minutes) for antegrade approach and mean DAP (459 +/- 304 Gycm(2)), mean AKr (6,881 +/- 4,243 mGy), and mean FT (82 +/- 40 minutes) for retrograde approach. The other significant values were median DAP (84 Gycm(2)), 75th percentile DAP (147 Gycm(2)), median AKr (1,160 mGy), and 75th percentile AKr (2,176 mGy) for antegrade approach and median DAP (422 Gycm(2)), 75th percentile DAP (552 Gycm(2)), median AKr (6,295 mGy), and 75th percentile AKr (8,064 mGy) for retrograde approach. In conclusion, a set of local DRL values from a large center were assessed. DRLs were provided for antegrade and retrograde approaches, reflecting the difference in difficulty from these 2 kinds of CTOs. The wide dose estimator values variations were explained through procedure complexity. The values obtained for the other more classic percutaneous coronary interventions were comparable with those found in the literature. PMID- 26275582 TI - Spherical statistics for characterizing the spatial distribution of deep brain stimulation effects on neuronal activity. AB - BACKGROUND: Computational models of deep brain stimulation (DBS) have played a key role in understanding its physiological mechanisms. By estimating a volume of tissue directly modulated by DBS, one can relate the neuronal pathways within those volumes to the therapeutic efficacy of a particular DBS setting. NEW METHOD: A spherical statistical framework is described to quantify and determine salient features of such morphologies using visualization techniques, empirical shape analysis, and formal hypothesis testing. This framework is shown using a 3D model of thalamocortical neurons surrounding a radially-segmented DBS array. RESULTS: We show that neuronal population volumes modulated by various DBS electrode configurations can be characterized by parametric distribution models, such as Kent and Watson girdle models. Distribution parameters were found to change with stimulus settings, including amplitude and radial distance from the DBS array. Increasing stimulation amplitude through a single electrode resulted in more diffuse neuronal activation and increased rotational symmetry about the mean direction of the activated population. When stimulation amplitude was held constant, the activated neuronal population distribution was more concentrated with distance from the DBS array and was also more rotationally asymmetric. We also show how data representation (e.g. stimulus-entrained cell body vs. axon node) can significantly alter model distribution shape. COMPARISON TO EXISTING METHODS: This statistical framework provides a quantitative method to analyze the spatial morphologies of DBS-induced effects on neuronal activity. CONCLUSIONS: The application of spherical statistics to assess spatial distributions of neuronal activity has potential usefulness for numerous other recording, labeling, and stimulation modalities. PMID- 26275584 TI - CT angiography of the lower extremity and coronary arteries using 256-section CT: a preliminary study. AB - AIM: To investigate the possible use of a 256-section computed tomography (CT) prospective electrocardiography (ECG)-gated wide volume scanning protocol for combined angiography of the lower extremity and coronary arteries, after a single injection of contrast medium, in patients with lower extremity peripheral arterial disease (PAD). MATERIALS AND METHODS: Thirty-four patients with suspected PAD underwent CT angiography (CTA) with a prospective ECG-gated protocol that covered the level of the tracheal bifurcation to the foot sole. Digital subtraction angiography (DSA) of the lower extremity arteries was performed on patients requiring therapeutic intervention. Image quality and stenosis of the coronary and lower extremity arteries were assessed. RESULTS: A total of 93.1% of the coronary segments were adequate for diagnosis. 17 (50%) patients showed coronary artery stenosis >=50%. A total of 95.8% of the lower extremity arterial segments were adequate for diagnosis. Twenty-eight patients with severe lower extremity arterial stenosis or occlusion underwent DSA. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CTA for the detection of significant lower arterial stenosis (>=50%) was 94.8%, 97.2%, 95.3%, 96.9%, and 96.3%, respectively. CONCLUSION: Using the prospective ECG-gated wide volume CTA protocol, images of the coronary and lower extremity arteries suitable for diagnosis can be acquired simultaneously after a single injection of contrast agent. In addition to accurately diagnosing PAD, combined angiography may be used to screen for coronary heart disease in patients with PAD. PMID- 26275585 TI - New insights into immune mechanisms underlying autoimmune diseases of the gastrointestinal tract. AB - Recent progresses in the immune mechanisms implicated in chronic inflammatory disorders have led to a more in-depth knowledge of the pathogenesis of autoimmune diseases of the gastrointestinal tract, including autoimmune atrophic gastritis, celiac disease, autoimmune enteropathy and ulcerative colitis. While the pathogenic role of specific circulating autoantibodies, i.e., respectively anti parietal cell, anti-tissue transglutaminase, anti-enterocyte and anti-neutrophil cytoplasmic, is still controversial, some common T-cell mediated mechanisms for inflammation - increase in T helper cell type 1/type 17 pro-inflammatory cytokines- or losing self-tolerance-abnormal regulatory T cell function - are recognized as crucial mediators of the tissue damage causing atrophy of the stomach mucosa in autoimmune atrophic gastritis, villous flattening of the small bowel in celiac disease and autoimmune enteropathy, and mucosal ulceration of the colon in ulcerative colitis. This review deals with novel advances in the immunological bases of the aforementioned autoimmune gastrointestinal disorders, and it also highlights immune mechanisms of progression from chronic inflammation to cancer and implications for new therapeutic targets. PMID- 26275586 TI - Persistent chorea in DYT6, due to anticholinergic therapy. PMID- 26275587 TI - When do infants understand that they can obtain a desired part of a composite object by grasping another part? AB - When do infants start to understand that they can grasp an object by its handle when the interesting part is out of reach? Whereas it is known from preferential looking tasks that already at three months of age infants show surprise when all parts of an object do not move together, little is known about when infants are able to use such knowledge in an active grasp situation. To answer this question we presented six, eight, and 10 month-old infants in a cross-sectional and a longitudinal study with a white cardboard handle within reach and a bright ball at the end of the handle and out of reach. A trick condition, where the handle and the ball seem attached but were not, was added to get an indication of the infant's expectation by observing a possible surprise reaction. Results show that 6-month-olds' most frequent first behaviors consisted in pointing toward the ball without grasping the handle, or grasping the handle without looking at the ball until it moved. In addition, they often did not look surprised in the trick condition. Eight- and 10-month-olds most often grasped the handle while looking at the ball, and showed clear surprise in the trick condition. This was interpreted as showing that around eight or 10 months, infants take a significant step in understanding the cohesiveness of composite objects during grasping. PMID- 26275588 TI - Lipid modulation of early G protein-coupled receptor signalling events. AB - Upon binding of extracellular ligands, G protein coupled-receptors (GPCRs) initiate signalling cascades by activating heterotrimeric G proteins through direct interactions with the alpha subunit. While the lipid dependence of ligand binding has previously been studied for one class A GPCR, the neurotensin receptor 1 (NTS1), the role the lipid environment plays in the interaction of activated GPCRs with G proteins is less well understood. It is therefore of interest to understand the balance of lipid interactions required to support both ligand binding and G protein activation, not least since some receptors have multiple locations, and may experience different membrane environments when signalling in the plasma membrane or during endocytosis. Here, using the sensitive biophysical technique of microscale thermophoresis in conjunction with nanodisc lipid bilayer reconstitution, we show that in more native lipid environments rich in phosphatidyl ethanolamine (PE), the Galphai1 subunit has a ~4-fold higher affinity for NTS1 than in the absence of native lipids. The G protein-receptor affinity was further shown to be dependent on the ligand-binding state of the receptor, with potential indication of biased signalling for the known antagonist SR142948A. Galphai1 also showed preferential interaction with empty nanodiscs of native lipid mixtures rich in PE by around 2- to 4-fold over phosphatidyl choline (PC)/phosphatidyl glycerol (PG) lipid mixtures. The lipid environment may therefore play a role in creating favourable micro-environments for efficient GPCR signalling. Our approach combining nanodiscs with microscale thermophoresis will be useful in future studies to elucidate further the complexity of the GPCR interactome. PMID- 26275589 TI - On the miscibility of cardiolipin with 1,2-diacyl phosphoglycerides: Binary mixtures of dimyristoylphosphatidylglycerol and tetramyristoylcardiolipin. AB - The thermotropic phase behavior and organization of model membranes composed of binary mixtures of the quadruple-chained, nominally dianionic phospholipid tetramyristoylcardiolipin (TMCL) with the double-chained, monoanionic phospholipid dimyristoylphosphatidylglycerol (DMPG) were examined by differential scanning calorimetry (DSC) and Fourier-transform infrared (FTIR) spectroscopy. The gel/liquid-crystalline phase transitions observed in these mixtures by DSC are generally rather broad and exhibit complex endotherms over a range of compositions. However, the phase transition temperatures and enthalpies exhibit nearly ideal behavior. Also, FTIR spectroscopic detection of the formation of stable and metastable DMPG-like lamellar crystalline (Lc) phases only at high DMPG levels upon low temperature annealing, and stable TMCL-like Lc phases at all higher TMCL concentrations, indicates that at low temperatures, laterally segregated domains of these two phospholipids must form, from which these different Lc phases nucleate and grow. Comparison of these results with those of a previous study of DMPE/TMCL mixtures (Frias et al., 2011) indicates that DMPG mixes slightly less well with TMCL than DMPE, perhaps because of the negative charge of the latter. However, in both binary mixtures, TMCL inhibits the formation of the Lc phase by DMPE even more strongly than for DMPG. Overall, our data suggest that TMCL and DMPG actually mix well across a broad temperature and composition range when the fatty acid chains of the two components are identical and only a modest (~17 degrees C) difference between their Lbeta/Lalpha phase transition temperatures exists. A recent DSC and X-ray diffraction study of DPPG/TMCL mixtures report similar results (Prossnigg et al., 2010). PMID- 26275590 TI - Disordered regions in transmembrane proteins. AB - The functions of transmembrane proteins in living cells are widespread; they range from various transport processes to energy production, from cell-cell adhesion to communication. Structurally, they are highly ordered in their membrane-spanning regions, but may contain disordered regions in the cytosolic and extra-cytosolic parts. In this study, we have investigated the disordered regions in transmembrane proteins by a stringent definition of disordered residues on the currently available largest experimental dataset, and show a significant correlation between the spatial distributions of positively charged residues and disordered regions. This finding suggests a new role of disordered regions in transmembrane proteins by providing structural flexibility for stabilizing interactions with negatively charged head groups of the lipid molecules. We also find a preference of structural disorder in the terminal--as opposed to loop--regions in transmembrane proteins, and survey the respective functions involved in recruiting other proteins or mediating allosteric signaling effects. Finally, we critically compare disorder prediction methods on our transmembrane protein set. While there are no major differences between these methods using the usual statistics, such as per residue accuracies, Matthew's correlation coefficients, etc.; substantial differences can be found regarding the spatial distribution of the predicted disordered regions. We conclude that a predictor optimized for transmembrane proteins would be of high value to the field of structural disorder. PMID- 26275591 TI - Anti-citrullinated protein antibodies promote apoptosis of mature human Saos-2 osteoblasts via cell-surface binding to citrullinated heat shock protein 60. AB - We hypothesized that anti-citrullinated protein antibodies (ACPAs) react with osteoblast surface citrullinated proteins and affect cell function, leading to joint damage in patients with rheumatoid arthritis (RA). First, we purified ACPAs by cyclic citrullinated peptide (CCP)-conjugated affinity column chromatography. The cognate antigens of ACPAs on Saos-2 cells, a sarcoma osteogenic cell line generated from human osteoblasts, were probed by ACPAs, and the reactive bands were analyzed using proteomic analyses. We found that ACPAs bind to Saos-2 cell membrane, and several protein candidates, including HSP60, were identified. We then cloned and purified recombinant heat shock protein 60 (HSP60) and citrullinated HSP60 (citHSP60) and investigated the effect of ACPAs on Saos-2 cell. We confirmed that HSP60 obtained from Saos-2 cell membrane were citrullinated and reacted with ACPAs, which induces Saos-2 cells apoptosis via binding to surface-expressed citHSP60 through Toll-like receptor 4 signaling. ACPAs promoted interleukin (IL)-6 and IL-8 expression in Saos-2 cells. Finally, sera from patients with RA and healthy controls were examined for their titers of anti-HSP60 and anti-citHSP60 antibodies using an enzyme-linked immunosorbent assay. The radiographic change in patients with RA was evaluated using the Genant modified Sharp scoring system. Patients with RA showed higher sera titers of anti citHSP60, but not anti-HSP60, antibodies when compared with controls. In addition, the anti-citHSP60 level was positively associated with increased joint damage in patients with RA. In conclusion, Saos-2 cell apoptosis was mediated by ACPAs via binding to cell surface-expressed citHSP60 and the titer of anti citHSP60 in patients with RA positively associated with joint damage. PMID- 26275592 TI - Clinical and Histological Basis for the Use of Nasolabial Tissues in the Surgical Management of Oral Submucous Fibrosis. AB - PURPOSE: The authors planned a clinical and histopathologic study to examine the behavior of nasolabial tissues (full-thickness skin flap) after being inset into the oral cavity for oral submucous fibrosis (OSMF) under the premise that skin that is foreign tissue to the oral cavity would be devoid of pathologic changes. MATERIALS AND METHODS: Fourteen patients with OSMF and mouth openings with an interincisal distance shorter than 28 mm were included. The flap was evaluated clinically for 10 years, during which biopsy specimen was obtained from the mucocutaneous junction of the inset flap for histopathologic examination. RESULTS: In this series, complications such as flap loss, infection, flap necrosis, obstructive sialadenitis, and damage to facial nerve branches were not observed. However, intraoral hair growth and extraoral scar at the donor site were seen in all patients, 3 of whom subsequently underwent scar revision. Histopathologically, the inset flap showed decreased keratinization and loss of adnexal structures. A mean mouth opening of 43.2 mm was achieved at 10 years postoperatively (mean increase, 24.4 mm). No relapse was encountered, even at the last follow-up. CONCLUSION: The nasolabial island flap or any other full thickness skin flap could be a viable and reliable option for reconstruction of intraoral defects from OSMF. PMID- 26275593 TI - Clinical Characteristics of Radiation-Induced Sarcoma of the Head and Neck: Review of 15 Cases and 323 Cases in the Literature. AB - PURPOSE: This retrospective study aimed to identify the clinical characteristics of radiation-induced sarcoma of the head and neck (RISHN) that could help in the early diagnosis of this rare disease. MATERIALS AND METHODS: From August 1995 through October 2014, 15 cases of RISHN presenting at the authors' department and 323 cases in the literature were reviewed. RESULTS: The incidence of RISHN was higher in men than in women (male-to-female ratio, 2.4:1). The mean latency was long (9.3 yr), and the tumor often occurred in middle age (50.0 yr old). Osteosarcoma was the predominant pathologic diagnosis (34.1%). The prognosis of RISHN was poor. CONCLUSION: RISHN is a serious long-term complication of radiotherapy and its incidence has been increasing in recent years. Owing to the long latency period, its early diagnosis is difficult to make. RISHN should be considered when a patient who has undergone radiotherapy presents with a mass, pain, or trismus in the irradiated field. PMID- 26275594 TI - Post-injury administration of allicin attenuates ischemic brain injury through sphingosine kinase 2: In vivo and in vitro studies. AB - Allicin, one of the main biologically active compounds derived from garlic, has been shown to exert various pharmacological activities and is considered to have therapeutic potential for many pathologic conditions. In the present study, we investigated the potential post-ischemic neuroprotective effects of allicin and its underlying mechanisms. Using a rat middle cerebral artery occlusion (MCAO) model, we found that intraperitoneal treatment with 50 mg/kg allicin significantly reduced brain infarct volume, attenuated cerebral edema and decreased the neurological deficit score. Allicin treatment also diminished TUNEL positive cells and inhibited the activation of caspase-3 after MCAO. These protective effects could be observed even if the administration was delayed to 6 h after injury. In addition, we evaluated the in vitro protective effects of allicin against oxygen glucose deprivation (OGD) induced neuronal injury in primary cultured cortical neurons. Allicin (50 MUM) increased neuronal viability, decreased lactate dehydrogenase (LDH) release and inhibited apoptotic neuronal death after OGD. These protective effects could be observed even if the administration was delayed to 4 h after injury. Furthermore, allicin significantly increased the expression of sphingosine kinases 2 (Sphk2) both in vivo and in vitro. Pretreatment with the Sphk2 inhibitor ABC294640 partially reversed the protective effects of allicin against MCAO and OGD injury, indicating that an Sphk2-mediated mechanism was involved in allicin-induced protection in our models. The combination of findings suggests that post-injury administration of allicin has potential as a neuroprotective strategy for ischemic stroke. PMID- 26275595 TI - Portugal at the cross road of international chronic respiratory programmes. PMID- 26275596 TI - Watershed model calibration framework developed using an influence coefficient algorithm and a genetic algorithm and analysis of pollutant discharge characteristics and load reduction in a TMDL planning area. AB - Manual calibration is common in rainfall-runoff model applications. However, rainfall-runoff models include several complicated parameters; thus, significant time and effort are required to manually calibrate the parameters individually and repeatedly. Automatic calibration has relative merit regarding time efficiency and objectivity but shortcomings regarding understanding indigenous processes in the basin. In this study, a watershed model calibration framework was developed using an influence coefficient algorithm and genetic algorithm (WMCIG) to automatically calibrate the distributed models. The optimization problem used to minimize the sum of squares of the normalized residuals of the observed and predicted values was solved using a genetic algorithm (GA). The final model parameters were determined from the iteration with the smallest sum of squares of the normalized residuals of all iterations. The WMCIG was applied to a Gomakwoncheon watershed located in an area that presents a total maximum daily load (TMDL) in Korea. The proportion of urbanized area in this watershed is low, and the diffuse pollution loads of nutrients such as phosphorus are greater than the point-source pollution loads because of the concentration of rainfall that occurs during the summer. The pollution discharges from the watershed were estimated for each land-use type, and the seasonal variations of the pollution loads were analyzed. Consecutive flow measurement gauges have not been installed in this area, and it is difficult to survey the flow and water quality in this area during the frequent heavy rainfall that occurs during the wet season. The Hydrological Simulation Program-Fortran (HSPF) model was used to calculate the runoff flow and water quality in this basin. Using the water quality results, a load duration curve was constructed for the basin, the exceedance frequency of the water quality standard was calculated for each hydrologic condition class, and the percent reduction required to achieve the water quality standard was estimated. The R(2) value for the calibrated BOD5 was 0.60, which is a moderate result, and the R(2) value for the TP was 0.86, which is a good result. The percent differences obtained for the calibrated BOD5 and TP were very good; therefore, the calibration results using WMCIG were satisfactory. From the load duration curve analysis, the WQS exceedance frequencies of the BOD5 under dry conditions and low-flow conditions were 75.7% and 65%, respectively, and the exceedance frequencies under moist and mid-range conditions were higher than under other conditions. The exceedance frequencies of the TP for the high-flow, moist and mid-range conditions were high and the exceedance rate for the high flow condition was particularly high. Most of the data from the high-flow conditions exceeded the WQSs. Thus, nonpoint-source pollutants from storm-water runoff substantially affected the TP concentration in the Gomakwoncheon. PMID- 26275597 TI - Toxicity characteristic leaching procedure over- or under-estimates leachability of lead in phosphate-amended contaminated soils. AB - In this study, Pb(NO3)2-, PbSO4-, or PbCO3-contaminated soils were treated with triple super phosphate (TSP) or phosphate rock (PR) and then subjected to the toxicity characteristic leaching procedure (TCLP) to assess Pb leachability. Soluble TSP resulted in the transformation of Pb into insoluble Pb phosphate precipitates in all contaminated soils, and the transformation increased with extended leaching times. Consequently, Pb concentrations in the TCLP leachates treated with TSP were reduced by 97.3-99.7% compared with the untreated soils, and Pb leaching decreased over the extraction time and did not reach equilibrium even after 96 h of extraction. Precipitation of Pb phosphate minerals in the less soluble PR-treated soil was limited, and Pb leaching was controlled by the dissolution of the Pb compounds, resulting in elevation of Pb in the TCLP leachate. Pb leaching continued to increase with time due to continuous dissolution of PbSO4 and PbCO3. The results indicated that Pb leaching is kinetically controlled by either Pb compound dissolution or phosphate mineral formation. The standard TCLP test using a designated 18 h incubation time can overestimate the leachability of Pb in soils contaminated with lead and amended with soluble TSP and underestimate the leachability of Pb in soils contaminated with Pb and amended with less soluble PR. Therefore, wide use of TCLP for assessing Pb leachability in all contaminated soils is insufficient, and development of a site-specific evaluation method is urgently needed. PMID- 26275598 TI - Arctic soil microbial diversity in a changing world. AB - The Arctic region is a unique environment, subject to extreme environmental conditions, shaping life therein and contributing to its sensitivity to environmental change. The Arctic is under increasing environmental pressure from anthropogenic activity and global warming. The unique microbial diversity of Arctic regions, that has a critical role in biogeochemical cycling and in the production of greenhouse gases, will be directly affected by and affect, global changes. This article reviews current knowledge and understanding of microbial taxonomic and functional diversity in Arctic soils, the contributions of microbial diversity to ecosystem processes and their responses to environmental change. PMID- 26275599 TI - Evaluation of Root Canal Debridement of Human Molars Using the GentleWave System. AB - INTRODUCTION: Studies using conventional endodontic protocols show insufficient cleaning of root canal systems, often resulting in persistent infection and treatment failure. The GentleWave System (GWS; Sonendo, Inc, Laguna Hills, CA) has been shown to result in a higher tissue dissolution rate in a study using bovine muscle. The purpose of this study was to compare the debridement efficacy of the GWS with a traditional method for cleaning root canals. METHODS: Forty five freshly extracted molars were randomly separated into 3 treatment groups (n = 15/group): group 1, no treatment; group 2, conventional rotary instrumentation and needle irrigation; and group 3, minimal instrumentation and the GWS treatment. Roots were prepared per standard histologic tissue processing after hematoxylin-eosin staining; sections were microscopically examined, and the percentage of soft tissue and debris remaining within the canals was morphometrically calculated. Images of the apical and middle regions of the roots were blindly analyzed. RESULTS: Significant differences (Welch's t test) were found between groups 2 and 3 in both apical (P = .0015) and middle (P = .0179) regions of the mesial roots of mandibular molars and mesiobuccal roots of maxillary molars. Groups 2 and 3 resulted in cleaning 67.8% and 97.2% of the mesiobuccal and mesiolingual root canals of mandibular molars and the mesiobuccal canals of maxillary molars, respectively, whereas the results were similar among groups 2 and 3 in the apical and middle regions of distal roots. Groups 2 and 3 revealed significantly less debris than group 1 (P < .005). CONCLUSIONS: The GWS showed a significantly greater cleaning capacity and reduction in residual debris within the mesiobuccal and mesiolingual canals of mandibular molars and the mesiobuccal canals of maxillary molars than those cleaned conventionally. PMID- 26275600 TI - Equilibrium distributions and simulation methods for age structured populations. AB - A simulation method is presented for the demographic and genetic variation of age structured haploid populations. First, we use matrix analytic methods to derive an equilibrium distribution for the age class sizes conditioned on the total population size. Knowledge of this distribution eliminates the need of a burn-in time in simulations. Next, we derive the distribution of the alleles at a polymorphic locus in various age classes given the allele frequencies in the total population and the age size composition. For the time dynamics, we start by simulating the dynamics for the total population. In order to generate the inheritance of the alleles, we derive their distribution conditionally on the simulated population sizes. This method enables a fast simulation procedure of multiple loci in linkage equilibrium. PMID- 26275601 TI - A two-phase Poisson process model and its application to analysis of cancer mortality among A-bomb survivors. AB - We consider a two-phase Poisson process model where only early successive transitions are assumed to be sensitive to exposure. In the case where intensity transitions are low, we derive analytically an approximate formula for the distribution of time to event for the excess hazard ratio (EHR) due to a single point exposure. The formula for EHR is a polynomial in exposure dose. Since the formula for EHR contains no unknown parameters except for the number of total stages, number of exposure-sensitive stages, and a coefficient of exposure effect, it is applicable easily under a variety of situations where there exists a possible latency time from a single point exposure to occurrence of event. Based on the multistage hypothesis of cancer, we formulate a radiation carcinogenesis model in which only some early consecutive stages of the process are sensitive to exposure, whereas later stages are not affected. An illustrative analysis using the proposed model is given for cancer mortality among A-bomb survivors. PMID- 26275602 TI - NHS Trusts' clinical research activity and overall CQC performance - Is there a correlation? AB - OBJECTIVE: Since the late 2000's, the creation of the National Institute for Health Research (NIHR) has transformed clinical research activity in the United Kingdom. This study sought to establish if there is a link between clinical research activity and overall NHS Trust performance. STUDY DESIGN: Retrospective cohort study. METHODS: Data for NHS Trust performance were obtained from public databases, namely the Care Quality Commission (CQC) 2013 risk rating for overall performance, and 2012-13 NIHR records for clinical research activity. RESULTS: Applying Spearman's rank analysis, none of the Trust categories showed a correlation with CQC risk rating: small hospitals, r = -0.062 (P = 0.76; n = 27); medium, r = -0.224 (P = 0.13; n = 47); large, r = -0.008 (P = 0.96; n = 57); academic, r = -0.18 (P = 0.41; n = 24). Similar results were observed when CQC risk rating was compared with the number of different clinical research studies conducted per Trust. CONCLUSION: The degree of NIHR National Portfolio clinical research activity is not significantly related to CQC risk rating, used as an indicator of overall NHS Trust performance. Other studies have previously shown that increased research activity correlates with improved mortality rates, one component of CQC risk rating scores. Alternative tools may have to be explored to evaluate the impact of clinical research on NHS Trusts and its patients. PMID- 26275603 TI - Synthesis and cytotoxic activity evaluation of some novel 1-(3-(aryl-4,5 dihydroisoxazol-5-yl)methyl)-4-trihalomethyl-1H-pyrimidin-2-ones in human cancer cells. AB - The synthesis of a series of 14 new 1-(3-(aryl-4,5-dihydroisoxazol-5-yl)methyl)-4 trihalomethyl-1H-pyrimidin-2-ones from the 1,3-dipolar cycloaddition reaction of 1-allyl-4-(trihalomethyl)pyrimidin-2(1H)-ones with aryl nitrile oxides is described. Also, the antiproliferative activity of the title compounds was tested against five human tumoral cell lines: MCF-7 breast cancer cell line, ER+ (estrogen receptor positive); HepG-2 (hepatoma); T-24 (bladder cancer); HCT-116 cell (colorectal carcinoma); and CACO-2. The preliminary results are promising, since three compounds presented IC50 values below 2 MUM, as well as moderate to high selectivity. PMID- 26275604 TI - Identifying and characterising key alternative splicing events in Drosophila development. AB - BACKGROUND: In complex Metazoans a given gene frequently codes for multiple protein isoforms, through processes such as alternative splicing. Large scale functional annotation of these isoforms is a key challenge for functional genomics. This annotation gap is increasing with the large numbers of multi transcript genes being identified by technologies such as RNASeq. Furthermore attempts to characterise the functions of splicing in an organism are complicated by the difficulty in distinguishing functional isoforms from those produced by splicing errors or transcription noise. Tools to help prioritise candidate isoforms for testing are largely absent. RESULTS: In this study we implement a Time-course Switch (TS) score for ranking isoforms by their likelihood of producing additional functions based on their developmental expression profiles, as reported by modENCODE. The TS score allows us to better investigate functional roles of different isoforms expressed in multi transcript genes. From this analysis, we find that isoforms with high TS scores have sequence feature changes consistent with more deterministic splicing and functional changes and tend to gain domains or whole exons which could carry additional functions. Furthermore these functions appear to be particularly important for essential regulatory roles, establishing functional isoform switching as key for regulatory processes. Based on the TS score we develop a Transcript Annotations Pipeline for Alternative Splicing (TAPAS) that identifies functional neighbourhoods of potentially interesting isoforms. CONCLUSIONS: We have identified a subset of protein isoforms which appear to have high functional significance, particularly in regulation. This has been made possible through the development of novel methods that make use of transcript expression profiles. The methods and analyses we present here represent important first steps in the development of tools to address the near complete lack of isoform specific function annotation. In turn the tools allow us to better characterise the regulatory functions of alternative splicing in more detail. PMID- 26275605 TI - Investigating the potential of Shikonin as a novel hypertrophic scar treatment. AB - BACKGROUND: Hypertrophic scarring is a highly prevalent condition clinically and results from a decreased number of apoptotic fibroblasts and over-abundant production of collagen during scar formation following wound healing. Our previous studies indicated that Shikonin, an active component extracted from Radix Arnebiae, induces apoptosis and reduces collagen production in hypertrophic scar-derived fibroblasts. In the study reported here, we further evaluate the potential use of Shikonin as a novel scar remediation therapy by examining the effects of Shikonin on both keratinocytes and fibroblasts using Transwell(r) co culture techniques. The underlying mechanisms were also revealed. In addition, effects of Shikonin on the expression of cytokines in Transwell co-culture "conditioned" medium were investigated. RESULTS: Our results indicate that Shikonin preferentially inhibits cell proliferation and induces apoptosis in fibroblasts without affecting keratinocyte function. In addition, we found that the proliferation-inhibiting and apoptosis-inducing abilities of SHI might be triggered via MAPK and Bcl-2/Caspase 3 signalling pathways. Furthermore, SHI has been found to attenuate the expression of TGF-beta1 in Transwell co-cultured "conditioned" medium. CONCLUSIONS: The data generated from this study provides further evidence that supports the potential use of Shikonin as a novel scar remediation therapy. PMID- 26275606 TI - STIM2 protects hippocampal mushroom spines from amyloid synaptotoxicity. AB - BACKGROUND: Alzheimer disease (AD) is a disease of lost memories. Mushroom postsynaptic spines play a key role in memory storage, and loss of mushroom spines has been proposed to be linked to memory loss in AD. Generation of amyloidogenic peptides and accumulation of amyloid plaques is one of the pathological hallmarks of AD. It is important to evaluate effects of amyloid on stability of mushroom spines. RESULTS: In this study we used in vitro and in vivo models of amyloid synaptotoxicity to investigate effects of amyloid peptides on hippocampal mushroom spines. We discovered that application of Abeta42 oligomers to hippocampal cultures or injection of Abeta42 oligomers directly into hippocampal region resulted in reduction of mushroom spines and activity of synaptic calcium-calmodulin-dependent kinase II (CaMKII). We further discovered that expression of STIM2 protein rescued CaMKII activity and protected mushroom spines from amyloid toxicity in vitro and in vivo. CONCLUSIONS: Obtained results suggest that downregulation of STIM2-dependent stability of mushroom spines and reduction in activity of synaptic CaMKII is a mechanism of hippocampal synaptic loss in AD model of amyloid synaptotoxicity and that modulators/activators of this pathway may have a potential therapeutic value for treatment of AD. PMID- 26275607 TI - General practitioners and sickness certification for injury in Australia. AB - BACKGROUND: Strong evidence supports an early return to work after injury as a way to improve recovery. In Australia, General Practitioners (GPs) see about 96 % of injured workers, making them the main gatekeepers to workers' entitlements. Most people with compensable injuries in Australia are certified as "unfit to work" by their GP, with a minority of patients certified for modified work duties. The reasons for this apparent dissonance between evidence and practice remain unexplored. Little is known about the factors that influence GP sickness certification behaviour in Australia. The aim of this study is to describe the factors influencing Australian GPs certification practice through qualitative interviews with four key stakeholders. METHODS: From September to December 2012, 93 semi-structured interviews were undertaken in Melbourne, Australia. Participants included GPs, injured workers, employers and compensation agents. Data were thematically analysed. RESULTS: Five themes describing factors influencing GP certification were identified: 1. Divergent stakeholder views about the GP's role in facilitating return to work; 2. Communication between the four stakeholder groups; 3. Conflict between the stakeholder groups; 4. Allegations of GPs and injured workers misusing the compensation system and 5. The layout and content of the sickness certificate itself. CONCLUSION: By exploring GP certification practice from the perspectives of four key stakeholders, this study suggests that certification is an administrative and clinical task underpinned by a host of social and systemic factors. The findings highlight opportunities such as practice guideline development and improvements to the sickness certificate itself that may be targeted to improve GP sickness certification behaviour and return to work outcomes in an Australian context. PMID- 26275609 TI - Psychosocial impact of involvement in the Special Olympics. AB - Existing evidence suggests that people with intellectual disabilities are vulnerable to low self-esteem leading to additional psychosocial issues such as social exclusion and stress. Previous research into the involvement of Special Olympics (SO) of people with intellectual disabilities has indicted positive psychosocial outcomes. Involvement in sport is known generally to have psychological and social benefits. This study aimed to compare the psychosocial impact of involvement in sport through the SO to no or limited sports involvement, for a sample of people with intellectual disabilities. A cross sectional design was employed comparing three groups, SO, Mencap Sports, and Mencap No Sports on the variables: Self-esteem, quality of life, stress levels and social networks. One hundred and one participants were recruited either through the SO or Mencap. Data were collected through the completion of validated questionnaires by one to one interviews with the participants. Analysis revealed that self-esteem, quality of life, and stress were all significantly associated with SO involvement. Logistic regression analysis was used to explore whether scores on these variables were able to predict group membership. Self-esteem was found to be a significant predictor of group membership, those in the SO having the highest self-esteem. The findings provide further evidence of a positive association between sport involvement and increased psychological wellbeing, especially for those involved in the SO. The implications of these findings for practice and future research into the relationship between sport and psychological wellbeing within the learning disabled population are considered. PMID- 26275608 TI - The rising burden of chronic conditions among urban poor: a three-year follow-up survey in Bengaluru, India. AB - BACKGROUND: Chronic conditions are on rise globally and in India. Prevailing intra-urban inequities in access to healthcare services compounds the problems faced by urban poor. This paper reports the trends in self-reported prevalence of chronic conditions and health-seeking pattern among residents of a poor urban neighborhood in south India. METHODS: A cross sectional survey of 1099 households (5340 individuals) was conducted using a structured questionnaire. The prevalence and health-seeking pattern for chronic conditions in general and for hypertension and diabetes in particular were assessed and compared with a survey conducted in the same community three years ago. The predictors of prevalence and health seeking pattern were analyzed through a multivariable logistic regression analysis. RESULTS: The overall self-reported prevalence of chronic conditions was 12%, with hypertension (7%) and diabetes (5.8%) being the common conditions. The self-reported prevalence of chronic conditions increased by 3.8 percentage point over a period of three years (OR: 1.5). Older people, women and people living below the poverty line had greater odds of having chronic conditions across the two studies compared. Majority of patients (89.3%) sought care from private health facilities indicating a decrease by 8.7 percentage points in use of government health facility compared to the earlier study (OR: 0.5). Patients seeking care from super specialty hospitals and those living below the poverty line were more likely to seek care from government health facilities. CONCLUSION: There is need to strengthen health services with a preferential focus on government services to assure affordable care for chronic conditions to urban poor. PMID- 26275610 TI - Uncertainty in the number of contributors in the proposed new CODIS set. AB - The probability that multiple contributors are detected within a forensic DNA profile improves as more highly polymorphic loci are analysed. The assignment of the correct number of contributors to a profile is important when interpreting the DNA profiles. In this work we investigate the probability of a mixed DNA profile appearing as having originated from a fewer number of contributors for the African American, Asian, Caucasian and Hispanic US populations. We investigate a range of locus configurations from the proposed new CODIS set. These theoretical calculations are based on allele frequencies only and ignore peak heights. We show that the probability of a higher order mixture (five or six contributors) appearing as having originated from one less individual is high. This probability decreases as the number of loci tested increases. PMID- 26275611 TI - Comparing different post-mortem human samples as DNA sources for downstream genotyping and identification. AB - The capability of DNA laboratories to perform genotyping procedures from post mortem remains, including those that had undergone putrefaction, continues to be a challenge in the Philippines, a country characterized by very humid and warm conditions all year round. These environmental conditions accelerate the decomposition of human remains that were recovered after a disaster and those that were left abandoned after a crime. When considerable tissue decomposition of human remains has taken place, there is no other option but to extract DNA from bone and/or teeth samples. Routinely, femur shafts are obtained from recovered bodies for human identification because the calcium matrix protects the DNA contained in the osteocytes. In the Philippines, there is difficulty in collecting femur samples after natural disasters or even human-made disasters, because these events are usually characterized by a large number of fatalities. Identification of casualties is further delayed by limitation in human and material resources. Hence, it is imperative to test other types of biological samples that are easier to collect, transport, process and store. We analyzed DNA that were obtained from body fluid, bone marrow, muscle tissue, clavicle, femur, metatarsal, patella, rib and vertebral samples from five recently deceased untreated male cadavers and seven male human remains that were embalmed, buried for ~ 1 month and then exhumed. The bodies had undergone different environmental conditions and were in various stages of putrefaction. A DNA extraction method utilizing a detergent-washing step followed by an organic procedure was used. The utility of bone marrow and vitreous fluid including bone marrow and vitreous fluid that was transferred on FTA((r)) cards and subjected to autosomal STR and Y STR DNA typing were also evaluated. DNA yield was measured and the presence or absence of PCR inhibitors in DNA extracts was assessed using Plexor((r))HY. All samples were amplified using PowerPlex((r))21 and PowerPlexY((r))23 systems and analyzed using the AB3500 Genetic Analyzer and the GeneMapper((r)) ID-X v.1.2 software. PCR inhibitors were consistently detected in bone marrow, muscle tissue, rib and vertebra samples. Amplifiable DNA was obtained in a majority of the samples analyzed. DNA recovery from 0.1g biological material was adequate for successful genotyping of most of the non-bone and bone samples. Complete DNA profiles were generated from bone marrow, femur, metatarsal and patella with 0.1 ng DNA template. Using 0.5 ng DNA template resulted in increased allele recovery and improved intra- and inter-locus peak balance. PMID- 26275612 TI - Population genetic analyses of the Powerplex((r)) Fusion kit in a cosmopolitan sample of Chubut Province (Patagonia Argentina). AB - Allele frequencies and forensic parameters for 22 autosomal STR loci and DYS391 locus included in the PowerPlex((r)) Fusion System kit were estimated in a sample of 770 unrelated individuals from Chubut Province, southern Patagonia. No significant deviations from Hardy-Weinberg equilibrium were observed after Bonferroni's correction. The combined power of discrimination and the combined probability of exclusion were >0.999999 and 0.999984, respectively. Comparisons with other worldwide populations were performed. The MDS obtained show a close biological relation between Chubut and Chile. The estimated interethnic admixture supports a high Native American contribution (46%) in the population sample of Chubut. These results enlarge the Argentine databases of autosomal STR and would provide a valuable contribution for identification tests and population genetic studies. PMID- 26275613 TI - Separation of Y-chromosomal haplotypes from male DNA mixtures via multiplex haplotype-specific extraction. AB - In forensic analysis, the interpretation of DNA mixtures is the subject of ongoing debate and requires expertise knowledge. Haplotype-specific extraction (HSE) is an alternative method that enables the separation of large chromosome fragments or haplotypes by using magnetic beads in conjunction with allele specific probes. HSE thus allows physical separation of the components of a DNA mixture. Here, we present the first multiplex HSE separation of a Y-chromosomal haplotype consisting of six Yfiler short tandem repeat markers from a mixture of male DNA. PMID- 26275614 TI - Genetic population study of Y-chromosome markers in Benin and Ivory Coast ethnic groups. AB - Ninety-six single nucleotide polymorphisms (SNPs) and seventeen short tandem repeat (STRs) were investigated on the Y-chromosome of 288 unrelated healthy individuals from populations in Benin (Bariba, Yoruba, and Fon) and the Ivory Coast (Ahizi and Yacouba). We performed a multidimensional scaling analysis based on FST and RST genetic distances using a large extensive database of sub-Saharan African populations. There is more genetic homogeneity in Ivory Coast populations compared with populations from Benin. Notably, the Beninese Yoruba are significantly differentiated from neighbouring groups, but also from the Yoruba from Nigeria (FST>0.05; P<0.01). The Y-chromosome dataset presented here provides new valuable data to understand the complex genetic diversity and human male demographic events in West Africa. PMID- 26275615 TI - Translating clinical trials from human to veterinary oncology and back. AB - In human medicine clinical trials are legally required for drug development and approval. In contrast, clinical trials in small animal cancer patients are less common and legally perceived as animal experiments. Comparative oncology has been recognized as a method to speed up the development of medications by introducing animal patients with naturally developing tumours. In such cases, using animal patients would generate more robust data, as their spontaneous disease resembles the "real life" situation and thus could be more likely to predict the situation in human disease. This would not only provide veterinary oncology access to the latest developments in medicine before they are available for clinical use in animals, but could also lead to generation of clinical data in animal patients that could be translated to humans. Nevertheless, there are several limitations to practical conduct of clinical trials in veterinary medicine. In this review, the possible application of similar standards of Good Clinical Practice as in human clinical drug development will be discussed in detail, with special consideration of legal and ethical aspects in Europe and the US. PMID- 26275616 TI - Leucobacter musarum subsp. musarum sp. nov., subsp. nov., Leucobacter musarum subsp. japonicus subsp. nov., and Leucobacter celer subsp. astrifaciens subsp. nov., three nematopathogenic bacteria isolated from Caenorhabditis, with an emended description of Leucobacter celer. AB - Three Gram-stain-positive, irregular-rod-shaped, non-motile, non-spore-forming bacteria were isolated from nematodes collected from Santa Antao, Cabo Verde (CBX151T, CBX152T) and Kakegawa, Japan (CBX130T). Based on 16S rRNA gene sequence similarity, strains CBX130T, CBX151T and CBX152T were shown to belong to the genus Leucobacter. This affiliation was supported by chemotaxonomic data (2,4 diaminobutyric acid in the cell wall; major respiratory quinones MK-10 and MK-11; major polar lipids phosphatidylglycerol and diphosphatidylglycerol; major fatty acids anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0). Strains CBX130T and CBX152T were found to share salient characteristics. Based on morphological, physiological, chemotaxonomic and biochemical analysis, strain CBX152T represents a novel species of the genus Leucobacter, for which the name Leucobacter musarum sp. nov. (type strain CBX152T = DSM 27160T = CIP 110721T) is proposed. Two subspecies of Leucobacter musarum sp. nov. are proposed: Leucobacter musarum sp. nov. subsp. musarum subsp. nov. (type strain CBX152T = DSM 27160T = CIP 110721T) and Leucobacter musarum sp. nov. subsp. japonicus subsp. nov. (type strain CBX130T = DSM 27158T = CIP 110719T). The third novel strain, CBX151T, showed genetic similarities with Leucobacter celer NAL101T indicating that these strains belong to the same species. Based on morphological, physiological, chemotaxonomic and biochemical differences it is proposed to split the species Leucobacter celer into two novel subspecies, Leucobacter celer subsp. celer subsp. nov. (type strain NAL101T = KACC 14220T = JCM 16465T) and Leucobacter celer subsp. astrifaciens subsp. nov. (type strain CBX151T = DSM 27159T = CIP 110720T), and to emend the description of Leucobacter celerShin et al. 2011. PMID- 26275618 TI - David Oliver: What should senior doctors be paid? PMID- 26275617 TI - Management of brain metastasis with magnetic resonance imaging and stereotactic irradiation attenuated benefits of prophylactic cranial irradiation in patients with limited-stage small cell lung cancer. AB - BACKGROUND: Magnetic resonance imaging (MRI) enables a more sensitive detection of brain metastasis and stereotactic irradiation (SRI) efficiently controls brain metastasis. In limited-stage small cell lung cancer (LS-SCLC), prophylactic cranial irradiation (PCI) in patients with good responses to initial treatment is recommended based on the survival benefit shown in previous clinical trials. However, none of these trials evaluated PCI effects using the management of brain metastasis with MRI or SRI. This study aimed to determine the effects of MRI and SRI on the benefits of PCI in patients with LS-SCLC. METHODS: The clinical records of pathologically proven SCLC from January 2006 to June 2013 in facilities equipped with or had access to SRI in Japan were retrospectively reviewed. Patients with LS-SCLC and complete or good partial responses after initial treatment were included in the study and analyzed by the Kaplan-Meier method. RESULTS: Of 418 patients with SCLC, 124 met criteria and were divided into patients receiving PCI (PCI group; n = 29) and those without PCI (non-PCI groups; n = 95). At baseline, ratios of patients with stage III were significantly advantageous for the non-PCI group, although younger age and high ratios of complete response and MRI confirmed absence of brain metastasis were advantageous for the PCI group. Neither median survival times (25 vs. 34 months; p = 0.256) nor cumulative incidence of brain metastasis during 2 years (45.5 vs. 30.8%; p = 0.313) significantly differed between the two groups. Moreover, these factors did not significantly differ among patients with stage III disease (25 vs. 26 months; p = 0.680, 42.3 vs. 52.3%; p = 0.458, respectively). CONCLUSION: PCI may be less beneficial in patients with LS-SCLC if the management with MRI and SRI is available. PMID- 26275619 TI - Developments in the Implementation of Acoustic Droplet Ejection for Protein Crystallography. AB - Acoustic droplet ejection (ADE) enables crystallization experiments at the low nanoliter scale, resulting in rapid vapor diffusion equilibration dynamics and efficient reagent usage in the empirical discovery of structure-enabling protein crystallization conditions. We extend our validation of this technology applied to the diverse physicochemical property space of aqueous crystallization reagents where dynamic fluid analysis coupled to ADE aids in accurate and precise dispensations. Addition of crystallization seed stocks, chemical additives, or small-molecule ligands effectively modulates crystallization, and we here provide examples in optimization of crystal morphology and diffraction quality by the acoustic delivery of ultra-small volumes of these cofactors. Additional applications are discussed, including set up of in situ proteolysis and alternate geometries of crystallization that leverage the small scale afforded by acoustic delivery. Finally, we describe parameters of a system of automation in which the acoustic liquid handler is integrated with a robotic arm, plate centrifuge, peeler, sealer, and stacks, which allows unattended high-throughput crystallization experimentation. PMID- 26275620 TI - Human mitochondrial MIA40 (CHCHD4) is a component of the Fe-S cluster export machinery. AB - Mitochondria play an essential role in synthesis and export of iron-sulfur (Fe-S) clusters to other sections of a cell. Although the mechanism of Fe-S cluster synthesis is well elucidated, information on the identity of the proteins involved in the export pathway is limited. The present study identifies hMIA40 (human mitochondrial intermembrane space import and assembly protein 40), also known as CHCHD4 (coiled-coil-helix-coiled-coil-helix domain-containing 4), as a component of the mitochondrial Fe-S cluster export machinery. hMIA40 is an iron binding protein with the ability to bind iron in vivo and in vitro. hMIA40 harbours CPC (Cys-Pro-Cys) motif-dependent Fe-S clusters that are sensitive to oxidation. Depletion of hMIA40 results in accumulation of iron in mitochondria concomitant with decreases in the activity and stability of Fe-S-containing cytosolic enzymes. Intriguingly, overexpression of either the mitochondrial export component or cytosolic the Fe-S cluster assembly component does not have any effect on the phenotype of hMIA40-depleted cells. Taken together, our results demonstrate an indispensable role for hMIA40 for the export of Fe-S clusters from mitochondria. PMID- 26275621 TI - Neuromuscular and Vascular Hamartoma of the Small Intestine: An Exuberant Reparative Process Secondary to Chronic Inflammation. AB - The term Neuromuscular and Vascular Hamartoma (NMVH) was initially coined by Fernando and McGovern in 1982 in their report of 2 cases. Whether this lesion is truly hamartomatous or represents a "burnt-out" phase of varying chronic pathologies has been debated since that time. Examples of NMVH-like proliferations have been reported in the setting of diaphragm disease, Crohn's disease, radiation, and ischemia. Herein we present the case of a 73-year-old female with partial small bowel obstruction and a past surgical history significant for cholecystectomy and abdominal hysterectomy. A computed tomography scan revealed an ill-defined mass with the same density as muscle extending into the mesentery, worrisome for malignancy and generating the differential of lymphoma versus metastatic disease. Upon laparotomy, a 2.5 cm, constrictive, predominantly mural-based mass was identified. The more proximal bowel was dilated, and there were dense serosal adhesions. Grossly, the transmural lesion had a tan-yellow cobweb-like cut surface and the overlying mucosa was flattened. Histologically, the lesion contained fascicles of smooth muscle, irregularly spaced large nerve bundles, and thick-walled vasculature in a haphazard arrangement within a hypocellular fibroadipose stroma. No stigmata of Crohn's disease were observed, and the uninvolved enteric tissue was unremarkable. The patient's medical history was negative for chronic nonsteroidal anti-inflammatory use and was otherwise unremarkable. This case of an NMVH-like lesion is presented as a reminder of benign mass-forming lesions causing bowel obstruction and suggests that such lesions may develop secondary to a chronic inflammatory process. PMID- 26275622 TI - Risk-taking behaviour in adolescents. 'Chance only favors the prepared mind'. PMID- 26275624 TI - Accuracy of combined dynamic contrast-enhanced magnetic resonance imaging and diffusion-weighted imaging for breast cancer detection: a meta-analysis. AB - BACKGROUND: Magnetic resonance imaging (MRI) is increasingly being used to examine patients with suspected breast cancer. PURPOSE: To determine the diagnostic performance of combined dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) for breast cancer detection. MATERIAL AND METHODS: A comprehensive search of the PUBMED, EMBASE, Web of Science, and Cochrane Library databases was performed up to September 2014. Statistical analysis included pooling of sensitivity and specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and diagnostic accuracy using the summary receiver operating characteristic (SROC). All analyses were conducted using STATA (version 12.0), RevMan (version 5.2), and Meta-Disc 1.4 software programs. RESULTS: Fourteen studies were analyzed, which included a total of 1140 patients with 1276 breast lesions. The pooled sensitivity and specificity of combined DCE-MRI and DWI were 91.6% and 85.5%, respectively. The pooled sensitivity and specificity of DWI-MRI were 86.0% and 75.6%, respectively. The pooled sensitivity and specificity of DCE MRI were 93.2% and 71.1%. The area under the SROC curve (AUC-SROC) of combined DCE-MRI and DWI was 0.94, the DCE-MRI of 0.85. Deeks testing confirmed no significant publication bias in all studies. CONCLUSION: Combined DCE-MRI and DWI had superior diagnostic accuracy than either DCE-MRI or DWI alone for the diagnosis of breast cancer. PMID- 26275623 TI - GC skew defines distinct RNA polymerase pause sites in CpG island promoters. AB - CpG islands (CGIs) are associated with over half of human gene promoters and are characterized by a unique chromatin environment and high levels of bidirectional transcriptional activity relative to surrounding genomic regions, suggesting that RNA polymerase (Pol II) progression past the CGI boundaries is restricted. Here we describe a novel transcriptional regulatory step wherein Pol II encounters an additional barrier to elongation distinct from the promoter-proximal pause and occurring at the downstream boundary of the CGI domain. For most CGI-associated promoters, Pol II exhibits a dominant pause at either the promoter-proximal or this distal site that correlates, both in position and in intensity, with local regions of high GC skew, a sequence feature known to form unique secondary structures. Upon signal-induced gene activation, long-range enhancer contacts at the dominant pause site are selectively enhanced, suggesting a new role for enhancers at the downstream pause. These data point to an additional level of control over transcriptional output at a subset of CGI-associated genes that is linked to DNA sequence and the integrity of the CGI domain. PMID- 26275625 TI - Drivers of information disclosure on health information exchange platforms: insights from an exploratory empirical study. AB - OBJECTIVE: The objective of this research is to empirically explore the drivers of patients' consent to sharing of their medical records on health information exchange (HIE) platforms. MATERIALS AND METHODS: The authors analyze a dataset consisting of consent choices of 20,076 patients in Western New York. A logistic regression is applied to empirically investigate the effects of patients' age, gender, complexity of medical conditions, and the role of primary care physicians on patients' willingness to disclose medical information on HIE platforms. RESULTS: The likelihood of providing consent increases by age (odds ratio (OR) = 1.055; P < .0001). Female patients are more likely to provide consent (OR = 1.460; P = .0003). As the number of different physicians involved in the care of the patient increases, the odds of providing consent slightly increases (OR = 1.024; P = .0031). The odds of providing consent is significantly higher for the patients whom a primary care physician has been involved in their medical care (OR = 1.323; P < .0001). CONCLUSION: Individual-level characteristics are important predictors of patients' willingness to disclose their medical information on HIE platforms. PMID- 26275626 TI - The duplicated paired box protein 7 (pax7) genes differentially transcribed during Japanese flounder (Paralichthys olivaceus) embryogenesis. AB - PAX are important regulators of developmental processes. PAX7 plays crucial roles in patterning of the dorsal central nervous system (CNS), neural crest (NC), and skeletal muscle. Here, we identified six spliced isoforms of pax7a and one pax7b and characterized their expression patterns. All of flounder Pax7a-1, Pax7a-2, Pax7a-3, and Pax7b contain a conserved paired domain (PD), an octapeptide motif (OP), and a paired type homeodomain (HD). However, the PD of Pax7a-4 and the HD of Pax7a-5 are not intact, and there is no HD in Pax7a-4 and Pax7a-6. pax7a and pax7b show distinct spatiotemporal expression patterns during embryogenesis. Whole-mount in situ hybridization demonstrates that the expression patterns of pax7a and pax7b are overlapping but distinguishable in the dorsal central nervous system. pax7a is expressed in most part of the brain and the neural tube, while pax7b is expressed exclusively in the diencephalon and the midbrain. In addition, pax7a is also expressed in the cranial NC and the trunk NC. RT-PCR results show that there were different expression patterns between the different isoforms. These results indicate subfunction partitioning of the duplicated pax7 genes. The duplicated pax7 may provide additional flexibility in fine-tuning neurogenesis and somitogenesis. PMID- 26275628 TI - False positivity of monospot test in an immunocompetent elderly woman with acute cytomegalovirus infection. AB - A 75-year-old woman presented with altered mental status, septic picture, and influenza-like symptoms. Initial investigations revealed atypical lymphocytosis, thrombocytopenia, elevated liver enzymes, and a positive monospot test result. Further investigation showed the Epstein-Barr virus viral capsid antibody IgM/IgG and Epstein-Barr virus DNA by polymerase chain reaction to be negative; however, interestingly her cytomegalovirus (CMV) IgM and IgG were positive, suggesting that her mononucleosis-like syndrome was due to acute CMV infection. Herein, we report the first case of a heterophile-positive mononucleosis syndrome caused by acute CMV infection in an elderly immunocompetent woman. This case conveys that monospot test can yield false-positive result in the setting of acute CMV infection. PMID- 26275627 TI - Molecular cloning, expression and single nucleotide polymorphisms of protein phosphatase 1 (PP1) in mandarin fish (Siniperca chuatsi). AB - In the wild, mandarin fish (Siniperca chuatsi) only feed on live prey fish, refusing dead prey. When reared in ponds, training will result in some mandarin fish accepting artificial diets. However, little is currently known about the molecular mechanism of the individual difference. Serine/threonine protein phosphatase 1 (PP1) is a suppressor of learning and long-term memory (LTM) in mammals. In the present study, the relationship between PP1 and the individual difference in acceptance of artificial diets in mandarin fish was investigated. The complete CDS (coding sequence) of four PP1 isoforms (PP1caa, PP1cab, PP1cb and PP1cc) were cloned in mandarin fish. The amino acid sequences of these PP1 isoforms are highly conserved in different species. The mRNA expressions of PP1caa and PP1cb in brain of artificial diet feeders were significantly higher than those in nonfeeders, suggesting the deficiency in the maintenance of long term memory of its natural food habit (live prey fish). The SNP loci in PP1caa and PP1cb were also found to be associated with the individual difference in acceptance of artificial diets in mandarin fish. These SNPs of PP1caa and PP1cb genes could be useful markers for gene-associated breeding of mandarin fish, which could accept artificial diets. In conclusion, different mRNA expression and SNPs of PP1caa and PP1cb genes in feeders and nonfeeders of artificial diets might contribute to understanding the molecular mechanism of individual difference in acceptance of artificial diets in mandarin fish. PMID- 26275629 TI - Paraplegia caused by aortic coarctation complicated with spinal epidural hemorrhage. AB - Aortic coarctation complicated with spinal artery aneurysm rupture is exceptionally rare and can be source of intraspinal hemorrhage with markedly poor prognosis. A 21-year-old man visited the emergency department because of chest and back pain along with immobility of bilateral lower limbs immediately after he woke up in the morning. Complete flaccid paraplegia and hypoesthesia in dermatome below bilateral T3 level and pain over axial region from neck to lumbar region were noted. A computed tomography excluded aortic dissection. Magnetic resonance imaging revealed a fusiform lesion involving the anterior epidural space from C7 to T2 level suspected of epidural hemorrhage, causing compression of spinal cord. He started intravenous corticosteroid but refused operation concerning the surgical benefits. Severe chest pain occurred with newly onset right bundle branch block that developed the other day. Coronary artery angiography revealed myocardial bridge of left anterior descending coronary artery at middle third and coarctation of aorta. He underwent thoracic endovascular aortic repair uneventfully. The patient was hemodynamically stable but with slow improvement in neurologic recovery of lower limbs. Aortic coarcation can cause paralysis by ruptured vascular aneurysms with spinal hemorrhage and chest pain that mimics acute aortic dissection. A history of hypertension at young age and aortic regurgitated murmurs may serve as clues for further diagnostic studies. Cautious and prudent evaluation and cross disciplines cares are essential for diagnosis and successful management of the disease. PMID- 26275630 TI - Effect of mild hypothermia on the increase of CD11b+ Gr-1+ myeloid-derived suppressor cells induced by lipopolysaccharide in a mouse model of sepsis. AB - PURPOSE: This study aimed to investigate the influence of mild hypothermia on the number of CD11b+ Gr-1+ myeloid-derived suppressor cells (MDSCs) induced by lipopolysaccharide (LPS) injection in mice with sepsis. METHODS: BALB/c mice were administered LPS to establish a mouse model of sepsis. Then, these mice were randomly divided into 3 groups: the mild hypothermia plus LPS group, the normothermia plus LPS group, and the LPS group. The normal control group was injected the same amount of 0.9% sodium chloride solution. The ratio of CD11b+ Gr 1+ MDSCs in the mouse spleen and bone marrow was determined at 6, 12, 24, 48, and 72 hours after LPS injection and after injected 0.9% sodium chloride solution. RESULTS: Compared with the control group, the number of MDSCs in the spleen in the sepsis group increased gradually, and the difference was significant at 12 hours after injection (P<.01). Moreover, the number of MDSCs was the lowest in the mild hypothermia group, and there was a significant difference than the other 2 groups at 48 hours (P<.01). The number of MDSCs in the bone marrow increased gradually, and the difference between the sepsis and control groups was significant at 24 hours (P<.01). The number of MDSCs in the mild hypothermia group was the lowest, and there was a statistically significant difference than the other 2 groups (P<.05). CONCLUSION: Mild hypothermia inhibited the production and accumulation of MDSCs induced by LPS administration in septic mice. PMID- 26275631 TI - Extracorporeal cardiopulmonary resuscitation in bedside echocardiography diagnosed massive pulmonary embolism. AB - Acute pulmonary embolism (PE) is one of the major causes of inhospital cardiac arrest as well as out-of-hospital cardiac arrest. Bedside diagnosis of acute PE in the emergency department (ED) can be challenging, especially in a cardiac arrest setting. Even if the early diagnosis of an acute massive PE had been made, hemodynamic instability may be worsened unless obstructive shock gets resolved. We present a case of a 46-year-old woman who developed pulseless electrical activity (PEA) after complaining of weakness and dyspnea in an ambulance, presumptively diagnosed as acute PE by bedside focused echocardiography. She received thrombolytic therapy and was rescued by extracorporeal cardiopulmonary resuscitation for recurrent PEA arrest in the ED. Focused bedside echocardiography provides a rapid diagnostic adjunct, and extracorporeal cardiopulmonary resuscitation can be a valuable rescue therapy for PEA arrest from massive PE. PMID- 26275632 TI - Therapeutic plasma exchange in poisoning: 8 years' experience of a university hospital. AB - INTRODUCTION AND AIM: This study examined the extracorporeal methods for the elimination of toxic substances in poisoned patients that are used by clinicians taking care of such patients. Here we present our experience in the use of therapeutic plasma exchange (TPE). To the best of our knowledge, this is the largest number of poisoning cases ever reported in a study. PATIENTS AND METHODS: This is a retrospective study conducted at the Cukurova University Faculty of Medicine, Department of Emergency Medicine, with the permission of the ethical committee of the medical faculty. The study includes patients who had undergone TPE because of poisoning between January 2007 and May 2015. We summarize the clinical data and outcomes of the patients with available files. RESULTS: A total of 36 cases among the 42 patients who underwent TPE in this 8-year period were included in the study. More than 20 identified toxic substances, most of which were pesticides, were found to be the causes of poisoning. Twenty-three healthy discharges and 12 deaths are discussed in the study. CONCLUSION: We believe that our study reports the largest ever number of poisoning cases treated with TPE in the literature. When applicable, TPE may be a promising extracorporeal elimination and treatment technique in poisoned patients when performed in selected cases. PMID- 26275633 TI - The role of interoceptive inference in theory of mind. AB - Inferring the intentions and beliefs of another is an ability that is fundamental for social and affiliative interactions. A substantial amount of empirical evidence suggests that making sense of another's intentional and belief states (i.e. theory of mind) relies on exteroceptive (e.g. visual and auditory) and proprioceptive (i.e. motor) signals. Yet, despite its pivotal role in the guidance of behaviour, the role of the observer's interoceptive (visceral) processing in understanding another's internal states remains unexplored. Predicting and keeping track of interoceptive bodily states - which inform intentions and beliefs that guide behaviour - is one of the fundamental purposes of the human brain. In this paper, we will focus on the role of interoceptive predictions, prescribed by the free energy principle, in making sense of internal states that cause another's behaviour. We will discuss how multimodal expectations induced at deep (high) hierarchical levels - that necessarily entail interoceptive predictions - contribute to inference about others that is at the heart of theory of mind. PMID- 26275634 TI - Does a low FODMAP diet improve symptoms in Mexican patients with IBS? PMID- 26275635 TI - Esophageal motility in eosinophilic esophagitis. AB - BACKGROUND: Eosinophilic esophagitis (EoE) is characterized by eosinophilic infiltration of the esophagus and is a potential cause of dysphagia and food impaction, most commonly affecting young men. Esophageal manometry findings vary from normal motility to aperistalsis, simultaneous contractions, diffuse esophageal spasm, nutcracker esophagus or hypotonic lower esophageal sphincter (LES). It remains unclear whether esophageal dysmotility plays a significant role in the clinical symptoms of EoE. AIM: Our aim is to review the pathogenesis, diagnosis, and effect of treatment on esophageal dysmotility in EoE. METHODS: A literature search utilizing the PubMed database was performed using keywords: eosinophilic esophagitis, esophageal dysmotility, motility, manometry, impedance planimetry, barium esophagogram, endoscopic ultrasound, and dysphagia. RESULTS: Fifteen studies, totaling 387 patients with eosinophilic esophagitis were identified as keeping in accordance with the aim of this study and included in this review. The occurrence of abnormal esophageal manometry was reported to be between 4 and 87% among patients with EoE. Esophageal motility studies have shown reduced distensibility, abnormal peristalsis, and hypotonicity of the LES in patients with EoE, which may also mimic other esophageal motility disorders such as achalasia or nutcracker esophagus. Studies have shown conflicting results regarding the presence of esophageal dysmotility and symptoms with some reports suggesting a higher rate of food impaction, while others report no correlation between motor function and dysphagia. CONCLUSIONS: Motility dysfunction of the esophagus in EoE has not been well reported in the literature and studies have reported conflicting evidence regarding the clinical significance of dysmotility seen in EoE. The correlation between esophageal dysmotility and symptoms of EoE remains unclear. Larger studies are needed to investigate the incidence of esophageal dysmotility, clinical implications, and effect of treatment on patients with EoE. PMID- 26275636 TI - Survey of Voice Acoustic Parameters in Iranian Female Teachers. AB - OBJECTIVES: Teachers are one of the professional voice users. Voice problems are common among them. Female teachers are known to have more voice problems than male ones. Furthermore, there are only few studies on the voice of Iranian female teachers. The present study investigated the acoustic parameters of voice in Iranian female teachers and compares them with nonteachers. METHODS: In this cross-sectional study, 90 Iranian female elementary teachers, 30-50 years old, and 90 Iranian female nonteachers in the same age were assessed between May 2010 and October 2011. Data collection was carried out, using the Dr. Speech software (subprogram: vocal assessment Version 4.0 from Tiger Electronics) at the speech therapy clinic under a comfortable phonation. Normal voice in practitioners was judged by the perceptual evaluation by a voice therapist and indirect laryngoscopy examination by an otorhinolaryngologist. Voice characteristics were assessed with GRBAS scale. The speech sample was sustained /a/ using habitual and constant vocal for 10 seconds. Three tokens from each subject were obtained. Then, each subject was asked to read a standard passage in Farsi. Eventually, the difference measures of F0, jitter, shimmer, harmonic to noise ratio (HNR), and maximum of phonation time (MPT) between two groups were investigated by statistics software SPSS 19.0 (IBM corp.2010). RESULTS: Results showed that the values of F0 were higher in teachers (210.03 Hz) than in nonteachers (194.11 Hz; P < 0.001). In addition, the values of perturbation measures were greater in teachers (jitter 0.32% and shimmer 4.63%) than those in the control group (jitter 0.22% and shimmer 3.15%; P < 0.001), but in HNR and MPT values, nonteachers showed higher levels (P < 0.001). The value of HNR in teachers was (18.84+/-1.56) but it was (21.3+/-1.73) in non-teachers and MPT value in teachers was (16.83+/ 3.65) and in non-teachers was (22.5+/-5.2). CONCLUSIONS: It can be concluded that vocal overuse, abuse, or misuse during teaching over a period of time result in achievement of inadequate phonatory pattern with excessive musculoskeletal tension, and the possible result is tissue changes in teacher's voice. In addition, acoustic analysis of voice parameters for teachers may significantly contribute to the objective voice examination of this group. PMID- 26275637 TI - Application of low-mixing energy input for the coagulation process. AB - Rapid-mixing tanks with mechanical mixers are a common design used in treatment plants. Yet, the role of such rapid-mixing systems on the effectiveness of the coagulation performance is unclear. This study looked at optimizing the direct energy used in the coagulation process for removal of natural dissolved organic matter (DOM). The role of coagulation mixing intensity (G-value) on total organic carbon (TOC) and turbidity removal was examined for the water types with high organic content, with a specific ultraviolet absorbance (SUVA) of at least 2-2.5 units of m(-1) of absorbance per mg/L. A standard jar test using ferric sulfate coagulant was performed to optimize the chemical condition in coagulation for removal of dissolved organics as well as particles. The jar test analysis at an acidic pH (4.5 +/- 0.3) required an iron dose <0.3 mM to arrive at an optimal coagulant concentration and resulted in above 75% of TOC removal. The influence of coagulation mixing on TOC and turbidity removal was evaluated at G varying from 0 to 1500 s(-1) at the optimized coagulant dose and pH conditions for enhanced coagulation. In this study, a combined effective removal of TOC and turbidity was achieved at a low-mixing intensity range of 110 s(-1) < G < 450 s( 1). Coagulation operated at G greater than 450 s(-1) showed negligible improvement in TOC removal. Minimizing energy consumption in enhanced coagulation is feasible at the proposed mixing intensity range (i.e., 110 s(-1) < G < 450 s( 1)), without sacrificing the effectiveness of DOM removal by coagulation. These findings represent an opportunity for energy savings for the water industry without sacrificing quality. PMID- 26275638 TI - Prevalence, morbidity, and current medical management of uterine leiomyomas. AB - BACKGROUND: Uterine leiomyoma is the most common pelvic tumor in women, but the actual prevalence is unknown. OBJECTIVES: To review the literature on the prevalence of uterine leiomyoma, presenting symptoms, and medical management. SEARCH STRATEGY: On April 1-30, 2014, a PubMed search for studies reported in English was conducted using the terms "uterine leiomyoma," "prevalence," and "symptoms." Another search was performed using the terms "uterine leiomyoma" and "treatment." SELECTION CRITERIA: All trial types other than internet-only studies were included. Animal studies were excluded from the prevalence/symptom review, but included in the medical management review. DATA COLLECTION AND ANALYSIS: Prevalence rates were recorded on the basis of imaging modality, cohort studied, ethnic origin, and age. MAIN RESULTS: Studies involving asymptomatic women revealed a trend in prevalence similar to that in symptomatic women, and showed that leiomyomas are more common in this cohort than previously recognized. Affected patients can present with many complaints, but no single symptom has been shown to be specific for this tumor. Various medical therapies are reviewed, summarizing efficacy and toxicity. CONCLUSIONS: Further research needs to be conducted on the prevalence in asymptomatic women. Current and future medical management options provide promising results in symptom reduction. PMID- 26275639 TI - A novel risk score that incorporates recipient and donor variables to predict 1 year mortality in the current era of lung transplantation. AB - BACKGROUND: In this study we sought to construct a novel scoring system to pre operatively stratify a patient's risk of 1-year mortality after lung transplantation (LTx) based on recipient- and donor-specific characteristics. METHODS: The UNOS database was queried for adult (>=18 years) patients undergoing LTx between May 1, 2005 and December 31, 2012. The population was randomly divided in a 4:1 fashion into derivation and validation cohorts. A multivariable logistic regression model for 1-year mortality was constructed within the derivation cohort. Points were then assigned to independent predictors (p < 0.05) based on relative odds ratios. Risk groups were established based on score ranges. RESULTS: During the study period, 9,185 patients underwent LTx and the 1 year mortality was 18.0% (n = 1,654). There was a similar distribution of variables between the derivation (n = 7,336) and validation (n = 1,849) cohorts. Of the 14 covariates included in the final model, 9 were ultimately allotted point values (maximum score = 70). The model exhibited good predictive strength (c = 0.65) in the derivation cohort and demonstrated a strong correlation between the observed and expected rates of 1-year mortality in the validation cohort (r = 0.87). The low-risk (score 0 to 11), intermediate-risk (score 12 to 21) and high risk (score >=22) groups had a 10.8%, 17.1% and 32.0% risk of mortality (p < 0.001), respectively. CONCLUSIONS: This is the first scoring system that incorporates both recipient- and donor-related factors to predict 1-year mortality after LTx. Its use could assist providers in the identification of patients at highest risk for poor post-transplant outcomes. PMID- 26275640 TI - The presentation and preliminary validation of KIWEST using a large sample of Norwegian university staff. AB - AIMS: The aim of the present paper is to present and validate a Knowledge Intensive Work Environment Survey Target (KIWEST), a questionnaire developed for assessing the psychosocial factors among people in knowledge-intensive work environments. METHODS: The construct validity and reliability of the measurement model where tested on a representative sample of 3066 academic and administrative staff working at one of the largest universities in Norway. RESULTS: Confirmatory factor analysis provided initial support for the convergent validity and internal consistency of the 30 construct KIWEST measurement model. However, discriminant validity tests indicated that some of the constructs might overlap to some degree. CONCLUSION: Overall, the KIWEST measure showed promising psychometric properties as a psychosocial work environment measure. PMID- 26275641 TI - Dose-response association between leisure time physical activity and work ability: Cross-sectional study among 3000 workers. AB - INTRODUCTION: Regular physical activity is important for longevity and health, but knowledge about the optimal dose of physical activity for maintaining good work ability is unknown. This study investigates the association between intensity and duration of physical activity during leisure time and work ability in relation to physical demands of the job. METHODS: From the 2010 round of the Danish Work Environment Cohort Study, currently employed wage earners with physically demanding work (n = 2952) replied to questions about work, lifestyle and health. Excellent (100 points), very good (75 points), good (50 points), fair (25 points) and poor (0 points) work ability in relation to the physical demands of the job was experienced by 18%, 40%, 30%, 10% and 2% of the respondents, respectively. RESULTS: General linear models that controlled for gender, age, physical and psychosocial work factors, lifestyle and chronic disease showed that the duration of high-intensity physical activity during leisure was positively associated with work ability, in a dose-response fashion (p < 0.001). Those performing ? 5 hours of high-intensity physical activity per week had on average 8 points higher work ability than those not performing such activities. The duration of low-intensity leisure-time physical activity was not associated with work ability (p = 0.5668). CONCLUSIONS: The duration of high-intensity physical activity during leisure time is associated in a dose-response fashion with work ability, in workers with physically demanding jobs. PMID- 26275642 TI - Economic Value of Improved Accuracy for Self-Monitoring of Blood Glucose Devices for Type 1 Diabetes in Canada. AB - OBJECTIVE: The objective was to simulate and compare clinical and economic outcomes of self-monitoring of blood glucose (SMBG) devices along error ranges and strip price. METHODS: We programmed a type 1 diabetes natural history and treatment cost-effectiveness model. In phase 1, using past evidence from in silico modeling validated by the Food and Drug Administration, we associated changes in SMBG error to changes in hemoglobin A1c (HbA1c) and separately, changes in severe hypoglycemia requiring an inpatient stay. In phase 2, using Markov cohort simulation modeling, we estimated clinical and economic outcomes from the Canadian payer perspective. The primary comparison was a SMBG device with strip price $0.73 Canadian dollars (CAD) and 10% error (exceeding accuracy requirements by International Organization for Standardization (ISO) 15197:2013) versus a SMBG device with strip price $0.60 CAD and 15% error (accuracy meeting ISO 15197:2013). Outcomes for the average patient, were quality-adjusted life years (QALYs), incremental cost-effectiveness ratios (ICERs), and budget impact. RESULTS: Assuming benefits translate into HbA1c improvements only, the ICER with 10% error versus 15% was $11 500 CAD per QALY. Assuming the benefits translate into reduced severe hypoglycemia requiring an inpatient stay only, an SMBG device with 10% error dominated (ie, less costly, more effective) an SMBG device with 15% error. The 3-year budget impact findings ranged from $0.004 CAD per member per month for HbA1c improvements to cost-savings for severe hypoglycemia reductions. CONCLUSIONS: From efficiency (cost-effectiveness) and affordability (budget impact) payer perspectives, investing in devices with improved accuracy (less error) appears to be an efficient and affordable strategy. PMID- 26275643 TI - Are Risk Indices Derived From CGM Interchangeable With SMBG-Based Indices? AB - BACKGROUND: The risk of hypo- and hyperglycemia has been assessed for years by computing the well-known low blood glucose index (LBGI) and high blood glucose index (HBGI) on sparse self-monitoring blood glucose (SMBG) readings. These metrics have been shown to be predictive of future glycemic events and clinically relevant cutoff values to classify the state of a patient have been defined, but their application to continuous glucose monitoring (CGM) profiles has not been validated yet. The aim of this article is to explore the relationship between CGM based and SMBG-based LBGI/HBGI, and provide a guideline to follow when these indices are computed on CGM time series. METHODS: Twenty-eight subjects with type 1 diabetes mellitus (T1DM) were monitored in daily-life conditions for up to 4 weeks with both SMBG and CGM systems. Linear and nonlinear models were considered to describe the relationship between risk indices evaluated on SMBG and CGM data. RESULTS: LBGI values obtained from CGM did not match closely SMBG-based values, with clear underestimation especially in the low risk range, and a linear transformation performed best to match CGM-based LBGI to SMBG-based LBGI. For HBGI, a linear model with unitary slope and no intercept was reliable, suggesting that no correction is needed to compute this index from CGM time series. CONCLUSIONS: Alternate versions of LBGI and HBGI adapted to the characteristics of CGM signals have been proposed that enable extending results obtained for SMBG data and using clinically relevant cutoff values previously defined to promptly classify the glycemic condition of a patient. PMID- 26275644 TI - The effects of music listening on psychosocial stress and maternal-fetal attachment during pregnancy. AB - OBJECTIVE: While music listening has been studied as an intervention to help reduce anxiety in pregnant women, few studies have explored the effect of music listening on pregnancy-specific stress relief. This study examines the effects of music listening on psychosocial stress and maternal-fetal attachment during pregnancy. DESIGN: A randomized controlled trial was implemented. A valid sample of 296 pregnant women in their second or third trimester was randomly distributed into an experimental group (n=145) and a control group (n=151). INTERVENTIONS: The experimental group received routine prenatal care and music listening. The control group received routine prenatal care only. MAIN OUTCOME MEASURES: Data were collected using a demographic form, Pregnancy Stress Rating Scale (PSRS), Perceived Stress Scale (PSS), and Maternal-Fetal Attachment Scale (MFAS). RESULTS: The post-test results identified a significantly lower level of psychosocial stress in the experimental group than in the control group, particularly in terms of the stresses related to baby care and changing family relationships and to maternal role identification. However, no statistically significant differences in terms of perceived stress and maternal-fetal attachment were found between the post-test results of the two groups. CONCLUSION: This study provides evidence in support of using of music in interventions designed to relieve psychosocial stress in prenatal women. IRB approval number: ER98223. PMID- 26275645 TI - A systematic review and meta-analysis of the effects of Qigong and Tai Chi for depressive symptoms. AB - BACKGROUND: Qigong and Tai Chi are the two most popular traditional Chinese exercises, known as mind-body movement therapies. Previous studies suggest that Qigong and Tai Chi may be beneficial in reducing depressive symptoms. This was the first study to systematically review and compare the effects of Qigong and Tai Chi on depressive symptoms. METHODS: A systematic search of six electronic databases was undertaken through to February 2014, for randomized controlled trials (RCTs) which reported depressive symptoms measured by a depressive symptom rating scale. The standardized mean difference in depressive symptoms score between Qigong or Tai Chi and a control group (at the end of follow-up) was extracted as a primary outcome. The secondary outcome was the standardized mean gain in symptom score (SMG) relative to the baseline from individual arms of the RCTs for various forms of care including Qigong, Tai Chi, usual care, other exercise, education and miscellaneous interventions. RESULTS: Thirty studies with a total of 2328 participants (823 males and 1505 females) were included. A significant effect was found for the Qigong interventions (Cohen's d -0.48 95% CI -0.48 to -0.12; SMG -0.52, 95% CI -0.79 to -0.26). There was no significant effect seen for Tai Chi for the primary endpoint. No mean change in symptom scores were seen for Tai Chi, usual care, other exercises, education and the 'miscellaneous' group in pre-post assessment in single arms. The Qigong results were found to be robust in sensitivity analyses. CONCLUSIONS: Qigong appears to be beneficial for reducing depressive symptom severity. However, given the low quality of the included studies and the documented evidence of publication bias, these results should be viewed cautiously. PMID- 26275646 TI - Risk in homeopathy: Classification of adverse events and homeopathic aggravations -A cross sectional study among Norwegian homeopath patients. AB - The registration of adverse events is important to identify treatment that might impose risk to patients. Homeopathic aggravation, a concept unique for homeopathy may impose a particular risk, as it is tolerant towards a worsening of the patients' symptoms. The aim of this study was to explore the classification of patient reported reactions as homeopathic aggravations or adverse drug reactions. DESIGN AND SETTING: In a cross sectional survey, patients were asked to register any reactions they had experienced 14 days after taking homeopathic remedies. Worsening of symptoms was classified as homeopathic aggravation if it was (i) an increase of the patients' existing symptoms (ii) and/or a feeling of well-being that emerged 1-3 days after taking the remedy (iii) and/or headache and/or fatigue accompanying these symptoms. RESULTS: A total of 26% of the participants reported worsening of symptoms. One third was classified as adverse events. Half of these were graded as minor and the other half as moderate according to the Common Terminology Criteria for Adverse Events. Two thirds were classified as homeopathic aggravations. Of these, 73% were classified as minor and 27% as moderate, giving a tendency towards milder severity for those classified as homeopathic aggravations (p=0.065). CONCLUSION: Patients reported a substantial part of the short-term reactions after taking homeopathic remedy as a worsening of symptoms. These reactions were classified as mild and moderate. Hence, the risk connected to homeopathic treatment is minor. More studies are needed to confirm the existence of homeopathic aggravation and how to classify the concept in a clinically meaningful way. PMID- 26275647 TI - Outcomes of Chinese herb medicine for the treatment of multidrug-resistant tuberculosis: a systematic review and meta-analysis. AB - Several studies have suggested that Chinese herb medicine (CHM) in combination with chemotherapy has efficacy in the treatment of multidrug-resistant tuberculosis (MDR-TB). The purpose of this meta-analysis was to assess the efficacy of CHM as a concomitant therapy for MDR-TB. Six databases were searched up to October 2014. Controlled trials comparing CHM combined with chemotherapy (treatment group) with chemotherapy alone (control group) for the treatment of MDR-TB were analyzed. Twenty studies, comprising 1823 patients across China, were included in this review. The meta-analysis showed CHM combined with chemotherapy was associated with a superiority in treatment success (odds ratio [OR], 1.33; 95% confidence interval [CI]: 1.15-1.54; P<0.001), and radiological improvement (OR, 1.32; 95% CI: 1.14-1.52; P<0.001). Patients who received CHM combined with chemotherapy were associated with a similar likely to relapse (OR, 0.88; 95% CI: 0.62-1.25, P=0.478). CHM combination with chemotherapy appeared to be associated with a low incidence of adverse effects for MDT-TB treatment. According to the pooled results and the poor quality of the included trials, it might be uncertainty that there was a superiority of CHM combined with chemotherapy for treating MDR-TB. More rigorous controlled trials are required to substantiate or refute these early findings. PMID- 26275648 TI - Effects of a standardized Ayurvedic formulation on diabetes control in newly diagnosed Type-2 diabetics; a randomized active controlled clinical study. AB - OBJECTIVES: The purpose of this study was to investigate the efficacy of a standardized polyherbal formulation consists of aqueous extracts from six herbs, in patients with Type-2 diabetes mellitus. DESIGN: Randomized, active control study. INTERVENTIONS: 93 patients, newly diagnosed with Type-2 diabetes mellitus were randomly allocated to group 1 (received polyherbal capsules 500 mg/day, up titrated weekly to a maximum of 3 g/day) and group 2 (received Metformin 500 mg/day, up titrated weekly to a maximum of 2 g/day). MAIN OUTCOME MEASURES: The primary endpoint was effect on the change from baseline in blood glucose (Fasting blood Glucose and Postprandial blood glucose), and glycosylated hemoglobin (HbA1c). The secondary outcome includes the effect on lipid levels, liver enzymes and renal function test. RESULTS: After 24 weeks, mean laboratory measured fasting and post prandial blood glucose showed a decrease of 25.52% and 24.22% in polyherbal formulation (PHF) treated group, compared to 31.46% and 24% decrease in Metformin treated group (estimated treatment difference -10.8; 95% CI -22.63 to 1.03 and -0.36; -12.1 to 11.38, respectively). Reduction in HbA1c was also similar for PHF and Metformin (estimated treatment difference 0.01; 95% CI -0.51 to 0.53). However, the decrease in the mean total cholesterol level was more pronounced in PHF treated group (estimated mean difference 61.3; 95% CI 55.32 to 67.28) than Metformin treated group (estimated mean difference 41.12; 95% CI 34.92 to 47.32). Also, there was statistical significance between the treatment groups in total cholesterol level at the end of six months treatment (estimated treatment difference 20.18; 95% CI 12.34 to 28.02). CONCLUSION: The study demonstrated that daily intake of this PHF decreased the glycemic level and improved lipid homeostasis, while maintaining the other serum biochemical levels to the normal, and therefore it may be useful for the patients with Type-2 diabetes. This trial is registered in the Clinical Trials Registry - India (CTRI) (CTRI/2014/03/004490). PMID- 26275649 TI - Effect of yoga on arterial stiffness in elderly subjects with increased pulse pressure: A randomized controlled study. AB - OBJECTIVE: We aimed to determine the effect of yoga on arterial function in elderly with increased pulse pressure (PP). DESIGN: Randomized controlled study with two parallel groups. PARTICIPANTS: Elderly subjects with PP>=60 mmHg (n=60). INTERVENTIONS: Yoga group (n=30) was assigned for yoga training and brisk-walking (BW) group (n=30) for brisk-walk with stretching exercise for 1h in the morning for 6 days in a week for 12 weeks. MAIN OUTCOME MEASURES: Arterial stiffness measures: Brachial-ankle pulse wave velocity (baPWV), Carotid-femoral pulse wave velocity (c-f PWV), aortic augmentation index (AIx@75), arterial stiffness index at brachial (bASI) and tibial arteries (aASI). Total serum nitric oxide concentration (NOx) as an index of endothelial function. Heart rate variability (HRV) measures: Low frequency and high frequency in normalized units (LFnu, HFnu) and LF/HF ratio. RESULTS: The mean between-group change (with 95% CI) in arterial stiffness: c-f PWV(m/s) [1.25(0.59-1.89); p<0.001], baPWV(m/s) [1.96(0.76-3.16), p<0.01], AIx@75 [3.07(0.24-5.89), p=0.066], aASI [8.3(4.06-12.53), p<0.001]; endothelial function index: NO(MUmol/L) [-9.03(-14.57 to -3.47), p<0.001]; SBP(mmHg) [14.23(12.03-16.44), p<0.001], DBP(mmHg) [0.1(-1.95-2.15), p=0.38], PP(mmHg) [14.07(11.2-16.92), p<0.001], MAP(mmHg) [4.7(3.08-6.32), p<0.001]; and cardiac autonomic function: LF(nu) [4.81(1.54-8.08), p<0.01], HF(nu) [-4.13(-7.57 to -0.69), p<0.01], LF/HF ratio [0.84(0.3-1.37), p<0.001], indicate significant difference in effects of two intervention on arterial stiffness, endothelial function, BP and cardiac autonomic activity. There was significant change within yoga group in vascular function, BP and autonomic function, while no significant change within-BW group was observed. CONCLUSION: Our findings suggest that yoga program offered was more effective than brisk-walk in reducing arterial stiffness along with BP in elderly individuals with increased PP. Yoga can also significantly reduce sympathetic activity and improve endothelial function with enhancement in bioavailability of NO. PMID- 26275650 TI - A supplemental report to a randomized cluster trial of a 20-week Sun-style Tai Chi for osteoarthritic knee pain in elders with cognitive impairment. AB - OBJECTIVE: This was a secondary data analysis of a cluster-randomized clinical trial that tested the efficacy of a 20-week Sun-style Tai Chi (TC) program in reducing pain in community-dwelling elders with cognitive impairment and knee osteoarthritis (OA). The study also examined whether elders' level of cognitive function was related to the outcomes of the TC program. METHOD: Elders (N=55) were recruited from 8 study sites. Each site was randomly assigned to participate in either a 20-week TC or an education program. Verbal report of pain was measured by a Verbal Descriptor Scale (VDS) at weeks 1, 5, 9, 13, 17 and 21 (designated as times 1-6). Pain behaviors and analgesic intake were also recorded at times 1-6. RESULTS: At post-test, scores on the VDS and observed pain behaviors were significantly better in the TC group than in the control group (p=0.008-0.048). The beneficial effects of TC were not associated with cognitive ability. CONCLUSION: These results suggest that TC can be used as an adjunct to pharmacological intervention to relieve OA pain in elders with cognitive impairment. TRIAL REGISTRATION: Clinical Trial.gov NCT01528566. PMID- 26275651 TI - Chuanxiong chadiao powder, a famous Chinese herbal prescription, for headache: A systematic review and meta-analysis. AB - BACKGROUND: Headache have been recognized as major causes of public ill-health, whereas there currently are the limitations of conventional therapies available. Chuanxiong Chadiao Powder (CXCP) is a well-known classic TCM herbal prescription with respect to treating headache for more than 1000 years. The objective of this study is to systematically assess the clinical efficacy and safety of CXCP for headache. METHODS: A systematic literature search in four databases, up to May of 2014, was performed to identify randomized controlled trials (RCTs), which compared CXCP monotherapy or adjunct therapy with western conventional medicine (WCM) or placebo for headache. The primary outcome measures were headache frequency, headache duration, pain intensity scales, globe assessment, patients self report outcomes, and quality of life. The second outcome measures were the total clinical effective rate and adverse events. The methodological quality of RCTs was assessed independently based on the 7 criteria recommended by the Cochrane Back Review Group. RESULTS: A total of 3680 participants were included in 37 eligible studies. The methodological quality was generally poor and there was only one high quality trial. Meta-analyses of the studies found that significant effects of CXCP for improving headache frequency and headache duration and the total clinical effective rate compared with WCM or placebo control in treating headache (P<0.01). Adverse event monitoring was reported in 22 studies (59%), while the other 15 studies (41%) did not mentioned. CONCLUSIONS: The evidence from present study is supported but limited for CXCP clinical use in the management of headache because of methodological flaws. Larger sample-sizes and rigorously designed RCTs are required in the future. PMID- 26275652 TI - The beneficial effects of the herbal medicine Di-huang-yin-zi (DHYZ) on patients with ischemic stroke: A Randomized, Placebo controlled clinical study. AB - OBJECTIVES: This study aimed to investigate the safety and therapeutic efficacy of herbal drug, Di Huang Yin Zi (DHYZ), in patients affected by ischemic stroke. METHODS: In this double blind, placebo-controlled study, a total of 100 patients with recent (less than 30 days) ischemic stroke were randomized to receive DHYZ or placebo for 12 weeks. Both groups also received rehabilitation therapy during the study period. As there were 13 dropouts, a total of 45 patients on DHYZ and 42 on placebo were available for analysis. The Fugl-Meyer Assessment (FMA) and Barthel index (BI) were assessed before treatment and at 4-week intervals. RESULTS: We observed that the FMA score and BI were increased, in both groups at week 4, 8 and 12 compared with the baseline. Furthermore, significantly better FMA score was observed in patients treated with DHYZ at week 8 and 12 (both P<0.05). BI was significantly higher in DHYZ group than in placebo group at weeks 12 (P<0.05). At week 12, the 95% Confidence Intervals (CI) of mean difference of FMA and BI also indicated that the differences between two groups were statistically significant. Compared to placebo, DHYZ produced significantly greater improvement in FMA grade at week 12 (44.4% versus 23.8%, chi(2)=4.09, P<0.05). CONCLUSIONS: DHYZ showed good efficacy, safety and tolerability in patients affected by ischemic stroke. We conclude that DHYZ may be a useful therapeutic option in patients with ischemic stroke. PMID- 26275653 TI - A randomized controlled trial of 6-week Chlorella vulgaris supplementation in patients with major depressive disorder. AB - BACKGROUND: Major depressive disorder (MDD) is a widespread psychiatric disorder with incapacitating symptoms. Oxidative stress has been identified to play a role in the pathophysiology of MDD. OBJECTIVE: To evaluate the therapeutic effectiveness of a chemically defined and antioxidant-rich Chlorella vulgaris extract (CVE) as adjunct to standard treatment in patients suffering from MDD. METHODS: Subjects with MDD diagnosis according to DSM-IV criteria who were receiving standard antidepressant therapy were assigned to add-on therapy with CVE (1800 mg/day; n=42), or continued standard antidepressant therapy alone (n=50) for a period of 6 weeks. Changes in the frequency of depressive symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS) and Beck Depression Inventory II (BDI-II) scale. RESULTS: There were significant reductions in total and subscale BDI-II and HADS scores in both CVE and control groups by the end of trial. The magnitude of reductions in total BDI-II score [ 4.14 (-5.30 to -2.97)] as well as physical [-2.34 (-2.84 to -1.84)] and cognitive [-1.12 (-1.62 to -0.61)] subscales were significantly greater in the CVE versus control group, however, reduction of the affective symptoms was greater in the control compared with the CVE group [0.95 (0.18-0.72)]. Total HADS [-3.71 (-4.44 to -2.98)] as well as individual subscales of depression [-1.46 (-2.02 to -0.90)] and anxiety [-2.25 (-2.74 to -1.76)] were reduced to a greater degree in the CVE group. CVE was well tolerated and no serious adverse event was reported. CONCLUSION: This pilot exploratory trial provides the first clinical evidence on the efficacy and safety of adjunctive therapy with CVE in improving physical and cognitive symptoms of depression as well as anxiety symptoms in patients who are receiving standard antidepressant therapy. PMID- 26275654 TI - Effectiveness and safety of traditional Chinese medicine on stable chronic obstructive pulmonary disease: A systematic review and meta-analysis. AB - OBJECTIVE: This study was intended to evaluate the efficacy and safety of Traditional Chinese Medicine (TCM) on stable chronic obstructive pulmonary disease (COPD). METHOD: A systematic review was conducted of clinical trials that compared TCM plus conventional medicine treatment versus conventional medicine treatment alone. Randomized controlled trials (RCTs) of clinical therapeutic studies on COPD by TCM were included. Searches were applied to the following electronic databases: The PubMed, the Cochrane Library,CNKI,CBM and VIP. No blinding and language restriction was used. All trials included were analyzed according to the criteria of the Cochrane Handbook. Review Manager 5.2 software was used for data analysis. RESULT: 37 randomized clinical trials enrolling 3212 patients were included. Follow-up duration ranged from 4 weeks to 1.5 years. Compared to conventional medicine treatment alone, TCM plus conventional medicine treatment showed improvement in forced expiratory volume in one second (FEV1) (MD 0.12 L; 95% CI 0.08 to 0.16), and less exacerbation (OR -0.86; 95% CI -1.13 to 0.60). TCM treatment also led to a statistically improvement in SGRQ score compared to placebo (MD -4.36; 95% CI -7.12 to -1.59). There was statistically significant difference in six-minute walk distance (MD 36.66 meters, 95% CI 24.57 to 48.74) found with TCM compared to placebo. CONCLUSION: Among patients with stable COPD, TCM plus conventional medical treatment therapy might be associated with reduction risk of exacerbation, improvement of lung function, better quality of life and higher exercise capacity. The results were limited by the methodological flaws of the studies. High quality studies are needed to provide clear evidence for the future use of TCM. PMID- 26275655 TI - A case-control, mono-center, open-label, pilot study to evaluate the feasibility of therapeutic touch in preventing radiation dermatitis in women with breast cancer receiving adjuvant radiation therapy. AB - BACKGROUND: Therapeutic touch (TT) is a non-invasive commonly used complementary therapy. TT is based on the use of hand movements and detection of energy field congestion to correct imbalances. Improvement in subjective symptoms in a variety of clinical trials has been seen with TT. The effect of TT during radiotherapy for breast cancer is unknown. METHODS: Women undergoing adjuvant radiation for Stage I/II breast cancer post conservative surgery were recruited for this cohort study. TT treatments were administered three times per week following radiation therapy. Feasibility was defined as an a priori threshold of 15 of 17 patients completing all TT treatments. The preventive effectiveness of TT was evaluated by documenting the 'time to develop' and the 'worst grade of radiation' dermatitis. Toxicity was assessed using NCIC CTC V3 dermatitis scale. Cosmetic rating was performed using the EORTC Breast Cosmetic Rating. The quality of life, mood and energy, and fatigue were assessed by EORTC QLQ C30, POMS, and BFI, respectively. The parameters were assessed at baseline, and serially during treatment. RESULTS: A total of 49 patients entered the study (17 in the TT Cohort and 32 in the Control Cohort). Median age in TT arm was 63 years and in control arm was 59 years. TT was considered feasible as all 17 patients screened completed TT treatment. There were no side effects observed with the TT treatments. In the TT Cohort, the worst grade of radiation dermatitis was grade II in nine patients (53%). Median time to develop the worst grade was 22 days. In the Control Cohort, the worst grade of radiation dermatitis was grade III in 1 patient. However, the most common toxicity grade was II in 15 patients (47%). Three patients did not develop any dermatitis. Median time to develop the worst grade in the control group was 31 days. There was no difference between cohorts for the overall EORTC cosmetic score and there was no significant difference in before and after study levels in quality of life, mood and fatigue. CONCLUSION: This study is the first evaluation of TT in patients with breast cancer using objective measures. Although TT is feasible for the management of radiation induced dermatitis, we were not able to detect a significant benefit of TT on NCIC toxicity grade or time to develop the worst grade for radiation dermatitis. In addition, TT did not improve quality of life, mood, fatigue and overall cosmetic outcome. PMID- 26275656 TI - Complementary and alternative medicines for diabetes mellitus management in ASEAN countries. AB - AIM: The aim of this study was to explore complementary or alternative practices used to promote health and reduce complications of patients with diabetes mellitus (DM). DESIGN: This qualitative, interpretative study recruited 30 adults including practitioners (n=15) and DM patients (n=15). The participants reside in the northeast of Thailand and in Vientiane of Lao People's Democratic Republic, and they have undergone treatment with at least a kind of complementary and alternative medicines (CAMs) for the care and management of DM. They were interviewed about their experiences, and the data were analyzed thematically. The study methodology was informed by hermeneutic phenomenology. RESULT: After several years of ineffective treatments, practitioners looked for an alternative to conventional health care to treat patients on long-term antidiabetic drugs, yet the patients suffered from progressive complications. They sought out health care that would more effectively meet their self-perceived needs in treatment particularly of a chronic disease such as DM. The result suggested that CAMs such as acupuncture, massage, exercise, and herbalism were able to meet their requirement in terms of health-care effectiveness obtained from experiences, additional cheap cost and availability in their community, and in accordance with the culture and lifestyles in the context of the ASEAN (Association of Southeast Asian Nations) community. CONCLUSION: The study explored and revealed the social perceptions of practitioners and patients using Chinese acupuncture, Thai massage, stretching exercise, and herbalism, as CAMs for DM management. The perceptions attributed to patient-practitioner consensus can hold a key to a more comprehensive health care, as a means to expand the boundaries for contemporary health-care provision. However, more study is needed in the future clinical trial research. PMID- 26275657 TI - Traditional herbal medicine as adjunctive therapy for breast cancer: A systematic review. AB - OBJECTIVES: To assess the effectiveness of traditional herbal medicine (THM) as adjunctive therapy for breast cancer as evidenced by randomized controlled trials (RCTs). METHODS: Five electronic English and Chinese databases were systematically searched up to February, 2014. All RCTs involving THM in combination with conventional cancer therapy for breast cancer were included. RESULTS: Eight RCTs involving 798 breast cancer patients were systematically reviewed. Three studies reported a significant difference in the improvement of quality of life (QOL) compared to the control group. Two studies reported an increase in the white blood cell count after treatment. Data on hot flashes and sleep quality were evaluated. However, no significant differences in immediate tumor response were observed. CONCLUSION: THM combined with conventional therapy in the treatment of breast cancer is efficacious in improving QOL and in decreasing the number of hot flashes per day. More research and well-designed, rigorous, large clinical trials are necessary to further address these issues. PMID- 26275658 TI - A new remedial approach to oxidant/antioxidant imbalance-based diseases: Wet cupping therapy. PMID- 26275659 TI - Response to "A new remedial approach to oxidant/antioxidant imbalance-based diseases: Wet-cupping therapy". PMID- 26275660 TI - Closing the gap between research and practice: Is it the key to increasing the impact of CAM research? PMID- 26275662 TI - Catalyst Chemical State during CO Oxidation Reaction on Cu(111) Studied with Ambient-Pressure X-ray Photoelectron Spectroscopy and Near Edge X-ray Adsorption Fine Structure Spectroscopy. AB - The chemical structure of a Cu(111) model catalyst during the CO oxidation reaction in the CO+O2 pressure range of 10-300 mTorr at 298-413 K was studied in situ using surface sensitive X-ray photoelectron and adsorption spectroscopy techniques [X-ray photoelectron spectroscopy (XPS) and near edge X-ray adsorption fine structure spectroscopy (NEXAFS)]. For O2:CO partial pressure ratios below 1:3, the surface is covered by chemisorbed O and by a thin (~1 nm) Cu2O layer, which covers completely the surface for ratios above 1:3 between 333 and 413 K. The Cu2O film increases in thickness and exceeds the escape depth (~3-4 nm) of the XPS and NEXAFS photoelectrons used for analysis at 413 K. No CuO formation was detected under the reaction conditions used in this work. The main reaction intermediate was found to be CO2(delta-), with a coverage that correlates with the amount of Cu2O, suggesting that this phase is the most active for CO oxidation. PMID- 26275661 TI - Rice WRKY4 acts as a transcriptional activator mediating defense responses toward Rhizoctonia solani, the causing agent of rice sheath blight. AB - WRKY transcription factors have been implicated in the regulation of transcriptional reprogramming associated with various plant processes but most notably with plant defense responses to pathogens. Here we demonstrate that expression of rice WRKY4 gene (OsWRKY4) was rapidly and strongly induced upon infection of Rhizoctonia solani, the causing agent of rice sheath blight, and exogenous jasmonic acid (JA) and ethylene (ET). OsWRKY4 is localized to the nucleus of plant cells and possesses transcriptional activation ability. Modulation of OsWRKY4 transcript levels by constitutive overexpression increases resistance to the necrotrophic sheath blight fungus, concomitant with elevated expression of JA- and ET-responsive pathogenesis-related (PR) genes such as PR1a, PR1b, PR5 and PR10/PBZ1. Suppression by RNA interference (RNAi), on the other hand, compromises resistance to the fungal pathogen. Yeast one-hybrid assay and transient expression in tobacco cells reveal that OsWRKY4 specifically binds to the promoter regions of PR1b and PR5 which contain W-box (TTGAC[C/T]), or W-box like (TGAC[C/T]) cis-elements. In conclusion, we propose that OsWRKY4 functions as an important positive regulator that is implicated in the defense responses to rice sheath blight via JA/ET-dependent signal pathway. PMID- 26275664 TI - Effects of food availability and climate on activity patterns of western black crested gibbons in an isolated forest fragment in southern Yunnan, China. AB - The critically endangered western black-crested gibbon (Nomascus concolor) is distributed in isolated habitat fragments in northern Vietnam, northwestern Laos, and southwestern China. To assess the behavioral adaptation of this species to forest fragments and its response to seasonal variation in food availability and climate, we present activity patterns of a group inhabiting an isolated forest based on two year-long studies in southern Yunnan, China. Annually, the gibbons spent nearly half of their active time resting, followed by moving and feeding. In both study periods, the time allocated to activities varied significantly between months, and was affected by food availability and climate factors. The group delayed retirement when tree fruit was abundant, and they decreased time spent moving and playing during periods of low fruit availability. In the cold months, the gibbons decreased time spent moving, and they decreased active time and resting time when rainfall was high. The results suggest that the group may seek to maximize net energy intake like energy maximizers when high quality food is most available, and adopt an energy-conserving strategy during periods of lower food availability and temperature. The gibbons showed similar diurnal variation in activity patterns to a group inhabiting a continuous forest at Dazhaizi, Mt. Wuliang, central Yunnan. However, they had a longer active period, and devoted more time to resting but less time to feeding. The individuals also spent lower percentages of time engaged in social behavior than those at Dazhaizi. These differences may be due to their smaller home range and unusual group composition caused by habitat fragmentation. PMID- 26275663 TI - Abnormalities of vascular structure and function in pediatric hypertension. AB - Hypertension is associated with adverse cardiovascular (CV) events in adults. Measures of vascular structure and function, including increased carotid intima media thickness (cIMT) and elevated arterial stiffness predict hard CV events in adulthood. Newer data suggest that abnormalities in target organ damage are occurring in adolescents and young adults with high blood pressure. In this review, we discuss the techniques for measuring vascular dysfunction in young people and the evidence linking blood pressure levels to this type of target organ damage. PMID- 26275665 TI - Erratum to: Transverse dental arch relationship at 9 and 12 years in children with unilateral cleft lip and palate treated with infant orthopedics: a randomized clinical trial (DUTCHCLEFT). PMID- 26275666 TI - Portrait of the Master Genetic Counselor Clinician: A Qualitative Investigation of Expertise in Genetic Counseling. AB - This study comprises an initial empirical description of personal and professional characteristics of master genetic counselors-those considered to be experts in the profession. Fifteen peer-nominated genetic counselors, actively engaged in providing clinical services to patients, participated in semi structured telephone interviews exploring their personal qualities, inspirations, and perspectives on professional development of expertise. Analysis using modified Consensual Qualitative Research methods yielded 7 domains and 33 categories. Findings indicate master genetic counselors have a strong passion for and dynamic commitment to the profession. They also have insatiable curiosity and are life-long learners who are reflective, self-aware, confident, and recognize their limitations. They are authentic and genuine, and consider their personality to be their counseling style. They form collaborative and interactive relationships with patients based on trust, and they have nuanced attunement to the complexity and multiple levels of the counseling process. Master genetic counselors have deep empathy and are inspired by patients and colleagues, and they derive personal meaning from their work. They are affected emotionally by their work, but effectively manage the emotional impact. They view their professional development as ongoing, influenced by colleagues, patients, mentoring, multicultural considerations, and their own family of origin. They also believe professional development of expertise occurs through critical reflection upon the experiences one accrues. Additional findings and their relationship to theory and research, study strengths and limitations, implication for training and practice, and research recommendation are discussed. PMID- 26275667 TI - Novel Induction Regimens in Multiple Myeloma. AB - Multiple myeloma is the second most common hematologic malignancy and predominantly affects the elderly. The introduction of novel agents such as thalidomide, lenalidomide, and bortezomib has improved progression-free survival, overall survival, and quality of life in myeloma patients. Next generation agents such as carfilzomib hold further promise for increased depth and length of remission. Autologous stem cell transplant remains a useful tool in the treatment of multiple myeloma, but not all patients are eligible for this procedure. As therapy becomes more effective, determination of the right therapy in the right patient becomes paramount. The focus of this review is a critical analysis of combinations of the novel agents in the treatment of newly diagnosed multiple myeloma in both transplant eligible and ineligible patients. PMID- 26275668 TI - Synergies and Tradeoffs Among Environmental Impacts Under Conservation Planning of Shale Gas Surface Infrastructure. AB - Hydraulic fracturing and related ground water issues are growing features in public discourse. Few have given much attention to surface impacts from shale gas development, which result from building necessary surface infrastructure. One way to reduce future impacts from gas surface development without radically changing industry practice is by formulating simple, conservation-oriented planning guidelines. We explore how four such guidelines affect the locations of well pads, access roads, and gathering pipelines on state lands in Pennsylvania. Our four guidelines aim to (1) reduce impacts on water, reduce impacts from (2) gathering pipelines and (3) access roads, and (4) reduce impacts on forests. We assessed whether the use of such guidelines accompanies tradeoffs among impacts, and if any guidelines perform better than others at avoiding impacts. We find that impacts are mostly synergistic, such that avoiding one impact will result in avoiding others. However, we found that avoiding forest fragmentation may result in increased impacts on other environmental features. We also found that single simple planning guidelines can be effective in targeted situations, but no one guideline was universally optimal in avoiding all impacts. As such, we suggest that when multiple environmental features are important in an area, more comprehensive planning strategies and tools should be used. PMID- 26275670 TI - Computational Analysis and Binding Site Identification of Type III Secretion System ATPase from Pseudomonas aeruginosa. AB - In many gram-negative bacteria, the type III secretion system (T3SS), as a virulence factor, is an attractive target for developing novel antibacterial. Regarding this, in our study, we aimed to identify the putative drug target for Pseudomonas aeruginosa, considering ATPase enzyme involved in the type III secretion system. Selective protein sequence of P. aeruginosa involved in the T3SS was retrieved from NCBI databases, and its homologues were subjected to phylogenetic analysis. Its association in T3SS was analyzed via STRING, and the 3D structure was determined by means of homology modeling followed by intensive optimization and validation. The binding site was predicted by 3DLigandSite and examined through molecular docking simulation by Autodock Vina with salicylidene acylhydrazide class of virulence-blocking compounds. PROCHECK analysis showed that 96.7 % of the residues were in the most favored regions, 1.9 % were in the additional allowed region, and 1.4 % were in the generously allowed region of the Ramachandran plot. The refined model yielded ERRAT scores of 88.124 and Verify3D value of 0.2, which indicates that the environmental profile of the model is good. The best binding affinity was observed by ME0055 compound, and ALA160, ALA161, GlY162, GLY163, GLY164, GLY165, SER166, THR167, TYR338, and PRO339 residues were found to be having complementary in the ligand-binding site. However, these findings should be further confirmed by wet lab studies for design a targeted therapeutic agent. PMID- 26275669 TI - The CellBorderTracker, a novel tool to quantitatively analyze spatiotemporal endothelial junction dynamics at the subcellular level. AB - Endothelial junctions are dynamic structures organized by multi-protein complexes that control monolayer integrity, homeostasis, inflammation, cell migration and angiogenesis. Newly developed methods for both the genetic manipulation of endothelium and microscopy permit time-lapse recordings of fluorescent proteins over long periods of time. Quantitative data analyses require automated methods. We developed a software package, the CellBorderTracker, allowing quantitative analysis of fluorescent-tagged cell junction protein dynamics in time-lapse sequences. The CellBorderTracker consists of the CellBorderExtractor that segments cells and identifies cell boundaries and mapping tools for data extraction. The tool is illustrated by analyzing fluorescent-tagged VE-cadherin the backbone of adherence junctions in endothelium. VE-cadherin displays high dynamics that is forced by junction-associated intermittent lamellipodia (JAIL) that are actin driven and WASP/ARP2/3 complex controlled. The manual segmentation and the automatic one agree to 90 %, a value that indicates high reliability. Based on segmentations, different maps were generated allowing more detailed data extraction. This includes the quantification of protein distribution pattern, the generation of regions of interest, junction displacements, cell shape changes, migration velocities and the visualization of junction dynamics over many hours. Furthermore, we demonstrate an advanced kymograph, the J-kymograph that steadily follows irregular cell junction dynamics in time-lapse sequences for individual junctions at the subcellular level. By using the CellBorderTracker, we demonstrate that VE-cadherin dynamics is quickly arrested upon thrombin stimulation, a phenomenon that was largely due to transient inhibition of JAIL and display a very heterogeneous subcellular and divers VE-cadherin dynamics during intercellular gap formation and resealing. PMID- 26275672 TI - Levels of Renibacterium salmoninarum antigens in resident and anadromous salmonids in the River Ellidaar system in Iceland. AB - In relation to stock enhancement programmes, wild salmon broodfish have been routinely screened for the presence of Renibacterium salmoninarum antigens (Rs Ag) for decades. A sudden increase in the prevalence of Rs-Ag experienced caused extensive problems to this industry as eggs from positive fish are discarded. The prevalence and level of Rs-Ag were examined in resident and anadromous salmonids in the River Ellidaar system and the progress of Rs-Ag in a cohort of salmon followed. Both prevalence and Rs-Ag levels were high in resident salmonids and emigrating salmon smolts in the river system. When the smolts re-entered their home river as adults the following summer, they were almost free of Rs-Ag, but the longer they stayed in the river, the more Rs-Ag they acquired; the majority being positive at spawning. This study demonstrates a high level of Rs-Ag in salmonids in the River Ellidaar system which significantly reduces in the salmon during its seawater phase. Accordingly, it seems ideal to sample salmon broodfish as soon as possible after ascending the river and subsequently transfer to Rs free environment for storage until stripping, which could result in lower Rs prevalence and minimize the problems that stock enhancement programmes have faced due to Rs-positive wild broodfish. PMID- 26275671 TI - ABO non-O type as a risk factor for thrombosis in patients with pancreatic cancer. AB - ABO blood type has previously been identified as a risk factor for thrombosis and pancreatic cancer (PC). The aim of the study is to demonstrate the associations between ABO blood type and other clinical factors with the risk of thromboembolism (TE) in patients with PC. We conducted a retrospective study in 670 patients with pathologically confirmed pancreatic adenocarcinoma at the University of Texas MD Anderson Cancer Center. Clinical information was retrieved from medical records. ABO blood type was determined serologically and/or genetically. Logistic regression models, Kaplan-Meier plot, log-rank test, and Cox proportional hazard regression models were employed in data analysis. The incidence of TE was 35.2% in 670 patients who did not have TE prior to cancer diagnosis. Pulmonary embolism (PE) and deep vein thrombosis (DVT) consisted 44.1% of the TE events. Non-O blood type, pancreatic body/tail tumors, previous use of antithrombotic medication, and obesity (body mass index >30 kg/m(2) ) were significant predictors for TE in general. Blood type A and AB, low hemoglobin level (<= 10 g/dL), obesity, metastatic tumor, and pancreatic body/tail tumors were significant predictors for PE and DVT. Patients with metastatic tumor or pancreatic body/tail tumors had a much higher frequency of early TE events (<= 3 months after cancer diagnosis); and early TE occurrence was a significant independent predictor for increased risk of death. These observations suggest that ABO non-O blood type is an independent predictor for TE in PC. A better understanding of the risk factors for TE in PC may help to identify patients who are most likely to benefit from prophylactic anticoagulation therapy. PMID- 26275674 TI - Antifolate Activity of Plant Polyphenols against Mycobacterium tuberculosis. AB - With the view of exploring phytochemicals as Mycobacterium tuberculosis (Mtb) dihydrofolate reductase inhibitors, known plant polyphenols from various classes were subjected to detailed docking studies. From this in-silico screening, seven polyphenols were selected and tested against Mtb H37 Rv in whole cell assays. The phytochemicals exhibited potential activity ranging from 3 to 183 um. These molecules were then tested against the pathogenic and human enzymes in a high throughput microtitre assay. Epigallocatechin gallate showed the best activity and selectivity. The in-silico analysis was in agreement with the assay results. Of these 7 polyphenols, 5 exhibiting minimum inhibitory concentration values of <=15 um were tested for synergistic activity with first line drug Ethambutol and second line folate inhibitor para-amino salicylic acid. Epigallocatechin gallate, Magnolol and Bakuchiol exhibited moderate synergistic association by lowering the minimum inhibitory concentration of these drugs. These simple phytochemicals could hence be considered as leads for further studies, or for preparation of semi-synthetic derivatives to be used in combination therapy, for increased anti tuberculosis activity after validation in-vivo. PMID- 26275675 TI - Five-dimensional ultrasound system for soft tissue visualization. AB - PURPOSE: A five-dimensional ultrasound (US) system is proposed as a real-time pipeline involving fusion of 3D B-mode data with the 3D ultrasound elastography (USE) data as well as visualization of these fused data and a real-time update capability over time for each consecutive scan. 3D B-mode data assist in visualizing the anatomy of the target organ, and 3D elastography data adds strain information. METHODS: We investigate the feasibility of such a system and show that an end-to-end real-time system, from acquisition to visualization, can be developed. We present a system that consists of (a) a real-time 3D elastography algorithm based on a normalized cross-correlation (NCC) computation on a GPU; (b) real-time 3D B-mode acquisition and network transfer; (c) scan conversion of 3D elastography and B-mode volumes (if acquired by 4D wobbler probe); and (d) visualization software that fuses, visualizes, and updates 3D B-mode and 3D elastography data in real time. RESULTS: We achieved a speed improvement of 4.45 fold for the threaded version of the NCC-based 3D USE versus the non-threaded version. The maximum speed was 79 volumes/s for 3D scan conversion. In a phantom, we validated the dimensions of a 2.2-cm-diameter sphere scan-converted to B-mode volume. Also, we validated the 5D US system visualization transfer function and detected 1- and 2-cm spherical objects (phantom lesion). Finally, we applied the system to a phantom consisting of three lesions to delineate the lesions from the surrounding background regions of the phantom. CONCLUSION: A 5D US system is achievable with real-time performance. We can distinguish between hard and soft areas in a phantom using the transfer functions. PMID- 26275673 TI - Sleep Hygiene and Recovery Strategies in Elite Soccer Players. AB - In elite soccer, players are frequently exposed to various situations and conditions that can interfere with sleep (e.g., playing night matches interspersed with 3 days; performing activities demanding high levels of concentration close to bedtime; use of products containing caffeine or alcohol in the period preceding bedtime; regular daytime napping throughout the week; variable wake-up times or bedtime), potentially leading to sleep deprivation. We outline simple, practical, and pharmaceutical-free sleep strategies that are coordinated to the constraints of elite soccer in order to promote sleep. Sleep deprivation is best alleviated by sleep extension; however, sleep hygiene strategies (i.e., consistent sleep pattern, appropriate napping, and active daytime behaviors) can be utilized to promote restorative sleep. Light has a profound impact on sleep, and sleep hygiene strategies that support the natural environmental light-dark cycle (i.e., red-light treatment prior to sleep, dawn simulation therapy prior to waking) and prevent cycle disruption (i.e., filtering short wavelengths prior to sleep) may be beneficial to elite soccer players. Under conditions of inordinate stress, techniques such as brainwave entrainment and meditation are promising sleep-promoting strategies, but future studies are required to ascertain the applicability of these techniques to elite soccer players. Consuming high-electrolyte fluids such as milk, high-glycemic index carbohydrates, some forms of protein immediately prior to sleep, as well as tart cherry juice concentrate and tryptophan may promote rehydration, substrate stores replenishment, muscle-damage repair and/or restorative sleep. The influence of cold water immersion performed close to bedtime on subsequent sleep is still debated. Conversely, the potential detrimental effects of sleeping medication must be recognized. Sleep initiation is influenced by numerous factors, reinforcing the need for future research to identify such factors. Efficient and individualized sleep hygiene strategies may consequently be proposed. PMID- 26275676 TI - Renal donors with prostate cancer, no longer a reason to decline. AB - OBJECTIVE: To fully assess the true risk of prostate cancer transmission in during renal transplantation. METHODS: A full review of all existing literature relevant to the topic. RESULTS: There has not been a single documented case of transmission of prostate cancer during renal transplant. Prostate cancer in deceased organ donors has an incidence estimated between 3% and 18.5% and over 100 transplants have been performed using organs from donor with proven prostate cancer without issue. CONCLUSION: Transmission of prostate cancer through kidney transplantation seems very unlikely. The risks of remaining on the waiting list are outweighed by a transmission risk and the potential benefit makes the case to have clear guidelines about donor prostate malignancy when accepting potential organs. PMID- 26275677 TI - Review of Thromboelastography in Neurocritical Care. PMID- 26275678 TI - Computer-aided identification, synthesis, and biological evaluation of novel inhibitors for botulinum neurotoxin serotype A. AB - Botulinum neurotoxins (BoNTs) are among the most potent biological toxin known to humans, and are classified as Category A bioterrorism agents by the Centers for Disease Control and prevention (CDC). There are seven known BoNT serotypes (A-G) which have been thus far identified in literature. BoNTs have been shown to block neurotransmitter release by cleaving proteins of the soluble NSF attachment protein receptor (SNARE) complex. Disruption of the SNARE complex precludes motor neuron failure which ultimately results in flaccid paralysis in humans and animals. Currently, there are no effective therapeutic treatments against the neurotoxin light chain (LC) after translocation into the cytosols of motor neurons. In this work, high-throughput in silico screening was employed to screen a library of commercially available compounds from ZINC database against BoNT/A LC. Among the hit compounds from the in silico screening, two lead compounds were identified and found to have potent inhibitory activity against BoNT/A-LC in vitro, as well as in Neuro-2a cells. A few analogs of the lead compounds were synthesized and their potency examined. One of these analogs showed an enhanced activity than the lead compounds. PMID- 26275679 TI - Antimalarial activity of prodrugs of N-branched acyclic nucleoside phosphonate inhibitors of 6-oxopurine phosphoribosyltransferases. AB - Acyclic nucleoside phosphonates (ANPs) that contain a 6-oxopurine base are good inhibitors of the human and Plasmodium falciparum 6-oxopurine phosphoribosyltransferases (PRTs), key enzymes of the purine salvage pathway. Chemical modifications, based on the crystal structures of several inhibitors in complex with the human PRTase, led to the design of a new class of inhibitors- the aza-ANPs. Because of the negative charges of the phosphonic acid moiety, their ability to cross cell membranes is, however, limited. Thus, phosphoramidate prodrugs of the aza-ANPs were prepared to improve permeability. These prodrugs arrest parasitemia with IC50 values in the micromolar range against Plasmodium falciparum-infected erythrocyte cultures (both chloroquine-sensitive and chloroquine-resistant Pf strains). The prodrugs exhibit low cytotoxicity in several human cell lines. Thus, they fulfill two essential criteria to qualify them as promising antimalarial drug leads. PMID- 26275680 TI - Synthesis and biological evaluation of (3',5'-dichloro-2,6-dihydroxy-biphenyl-4 yl)-aryl/alkyl-methanone selective CB2 inverse agonist. AB - Cannabinoid receptor 2 (CB2) selective agonists and inverse agonists possess significant potential as therapeutic agents for regulating inflammation and immune function. Although CB2 agonists have received the greatest attention, it is emerging that inverse agonists also manifest anti-inflammatory activity. In process of designing new cannabinoid ligands we discovered that the 2,6-dihydroxy biphenyl-aryl methanone scaffold imparts inverse agonist activity at CB2 receptor without functional activity at CB1. To further explore the scaffold we synthesized a series of (3',5'-dichloro-2,6-dihydroxy-biphenyl-4-yl)-aryl/alkyl methanone analogs and evaluated the CB1 and CB2 affinity, potency, and efficacy. The studies reveal that an aromatic C ring is required for inverse agonist activity and that substitution at the 4 position is optimum. The resorcinol moiety is required for optimum CB2 inverse agonist activity and selectivity. Antagonist studies against CP 55,940 demonstrate that the compounds 41 and 45 are noncompetitive antagonists at CB2. PMID- 26275681 TI - Discovery and structure of a new inhibitor scaffold of the autophagy initiating kinase ULK1. AB - Energy homeostasis in eukaryotic cells is a complex and fundamental process that is misregulated in several human diseases. A key component of energy regulation is a process called autophagy that involves the recycling of cellular components. There has been much recent interest in studying the mechanism of autophagy to understand an important cellular process and to evaluate the therapeutic potential in targeting autophagy. Activation of a kinase called ULK1 initiates autophagy by driving downstream pathways that lead to the formation of double membrane bound vesicles that surround the cellular contents that are to be degraded. Here, we report the discovery of an inhibitor of ULK1 with improved selectivity and a high-resolution crystal structure of the compound bound to the kinase, which will be useful tools for studying autophagy in cells. PMID- 26275682 TI - Generation of monoclonal antibodies specific of the postfusion conformation of the Pneumovirinae fusion (F) protein. AB - Paramyxovirus entry into cells requires fusion of the viral and cell membranes mediated by one of the major virus glycoproteins, the fusion (F) glycoprotein which transits from a metastable pre-fusion conformation to a highly stable post fusion structure during the membrane fusion process. F protein refolding involves large conformational changes of the protein trimer. One of these changes results in assembly of two heptad repeat sequences (HRA and HRB) from each protomer into a six-helix bundle (6HB) motif. To assist in distinguishing pre- and post-fusion conformations of the Pneumovirinae F proteins, and as extension of previous work (Palomo et al., 2014), a general strategy was designed to obtain polyclonal and particularly monoclonal antibodies specific of the 6HB motif of the Pneumovirinae fusion protein. The antibodies reported here should assist in the characterization of the structural changes that the F protein of human metapneumovirus or respiratory syncytial virus experiences during the process of membrane fusion. PMID- 26275683 TI - Intranasal corticosteroids do not affect intraocular pressure or lens opacity: a systematic review of controlled trials. AB - BACKGROUND: Intranasal corticosteroids (INCS) are prescribed for the long-term prophylactic treatment of inflammatory upper airway conditions. Although some systemic absorption can occur via topical routes, the clinical relevance is controversial. The effects of orally administered corticosteroids on intraocular pressure (IOP) and lens opacity (LO) are well established, but the impact of the INCS is less well defined. This study aims to systematically review the literature for evidence of adverse occular events with INCS use. METHODOLOGY: A systematic review of literature from Medline and Embase databases (January 1974 to 21st of November 2013) was performed. Using the PRISMA guidelines, all controlled clinical trials of patients using INCS, that reported original measures of IOP, LO, glaucoma or cataract incidences were included. Studies with adjuvant administration of oral, inhaled and intravenous steroids were excluded. RESULTS: 665 articles were retrieved with 137 were considered for full-text review. Of these, 116 (85%) were literature reviews and two were case reports. 19 studies (10 RCTs, 1 case-control, 8 case series) were included for the qualitative review, of which 18 reported data on IOP and 10 on cataract/LO. None (n=0) of the 10 RCT reporting data on glaucoma or IOP demonstrated changes in IOP compared to control. Also none (n=0) of the 6 RCTs reporting cataract or lens opacity demonstrated changes compared to control. CONCLUSION: Data from studies with low levels of bias, do not demonstrate a clinically relevant impact of INCS on neither ocular pressure, glaucoma, lens opacity nor cataract formation. PMID- 26275684 TI - Simultaneous monitoring of intratidal compliance and resistance in mechanically ventilated piglets: A feasibility study in two different study groups. AB - Compliance measures the force counteracting parenchymal lung distension. In mechanical ventilation, intratidal compliance-volume (C(V))-profiles therefore change depending on PEEP, tidal volume (VT), and underlying mechanical lung properties. Resistance counteracts gas flow through the airways. Due to anatomical linking between parenchyma and airways, intratidal resistance-volume (R(V))-profiles are hypothesised to change in a non-linear way as well. We analysed respiratory system mechanics in fifteen piglets with lavage-induced lung injury and nine healthy piglets ventilated at different PEEP/VT-settings. In healthy lungs, R(V)-profiles remained mostly constant and linear at all PEEP settings whereas the shape of the C(V)-profiles showed an increase toward a maximum followed by a decrease (small PEEP) or volume-dependent decrease (large PEEP). In the lavage group, a large drop in resistance at small volumes and slow decrease toward larger volumes was found for small PEEP/VT-settings where C(V) profiles revealed a volume-dependent increase (small PEEP) or a decrease (large PEEP and large VT). R(V)-profiles depend characteristically on PEEP, VT, and possibly whether lungs are healthy or not. Curved R(V)-profiles might indicate pathological changes in the underlying mechanical lung properties and/or might be a sign of derecruitment. PMID- 26275685 TI - Quantifying the shape of the maximal expiratory flow-volume curve in mild COPD. AB - Maximal expiratory flow-volume (MEFV) curve evaluation using absolute and percent predicted values of flow and volume are used to diagnose respiratory disease, but the shape of the curve is rarely used. Three mathematical methods were used to quantify shape of MEFV curves in subjects with mild COPD (n=19) and matched healthy controls (n=15). Those with mild COPD had a significantly greater slope ratio (SR) (1.90 +/- 0.24 vs. 1.28 +/- 0.32) and Beta-angle (160 +/- 6.7 vs. 186 +/- 15.0) compared to healthy individuals (p<0.05). The flow-ratio method showed no difference between groups. A significant positive SR-volume relationship during expiration was observed in a greater number of mild COPD subjects (94%) compared to controls (20%) (p<0.001). With its increased spatial resolution and the potential to discern etiology behind specific curvature, we suggest using the SR method when available. The change in SR throughout expiration could help identify those who fall within the lower limit of normal lung function and those who may have pathological obstruction. PMID- 26275686 TI - Assessment of the effect of cyclosporine-A 0.05% emulsion on the ocular surface and corneal sensation following cataract surgery. AB - AIM: To assess the effect of cyclosporine-A (CsA) 0.05% ophthalmic emulsion on corneal sensation and ocular surface problems following cataract surgery. DESIGN: Prospective, randomized, double masked clinical trial. METHODS: Consecutive case series of patients attending for bilateral cataract surgery. Subject's eyes were randomized to receive either topical CsA or carboxymethylcellulose 0.5% (CMC) eye drops twice daily for one month following routine cataract surgery. Subjective and objective assessments were performed pre-operatively, one week, and one month after surgery. Primary safety parameters included best spectacle-corrected visual acuity and incidence of adverse events. Objective assessments included tests of tear film (osmolarity, tear break-up time, and Schirmer's type-I test), ocular surface staining, corneal sensitivity and a subjective assessment: ocular surface disease index (OSDI) questionnaire. RESULTS: 30 subjects (60 eyes) were recruited. At one month following cataract surgery, osmolarity, ocular surface staining, TBUT, Schirmer's results showed a greater improvement after CsA drops compared to CMC and this was statistically significant for all measures (p<0.05). All corneal sensation measurements were reduced after one week and one month. Eyes receiving CsA had higher recovery of corneal sensation at both time points post operatively and this was statistically significant at one month. OSDI questionnaire results did not show a statistically significant difference between the two eyes. CONCLUSIONS: CsA is effective and safe in the management of ocular surface problems after cataract surgery and allows faster recovery of corneal sensation. This recovery of sensation may be relevant to the improvement in ocular surface problems in all patients. PMID- 26275687 TI - Utility of VerifyNow for Point-of-Care Identification of an Aspirin Effect Prior to Emergency Cardiac Surgery. AB - BACKGROUND: Patients with cardiovascular disease are frequently on aspirin, which may place them at risk for bleeding during surgical procedures. The utility of the VerifyNow test to rapidly identify an aspirin effect and predict bleeding risk prior to cardiac surgery was explored. METHODS: A retrospective study was performed of patients on a clinical pathology consultation service that provides laboratory and transfusion support for patients undergoing major cardiac surgery. Patients who had VerifyNow testing for aspirin effect were selected. RESULTS: A total of 88 patients had VerifyNow aspirin testing during the study period. The VerifyNow test correctly identified 52/63 (82.5%) patients with documented aspirin use, and missed 11/63 (17.5%) of aspirin users. Light transmission aggregometry (LTA) showed an aspirin effect in the majority of aspirin users missed by the VerifyNow assay. Moderate correlations were found between LTA and VerifyNow. Low aspirin reaction units were not associated with significant bleeding in these cardiac surgery patients. CONCLUSIONS: We propose the VerifyNow assay for point-of-care identification of aspirin effect prior to emergency surgeries. PMID- 26275688 TI - A Risk Score Derived from the Analysis of a Cluster of 27 Serum Inflammatory Cytokines to Predict Long Term Outcome in Patients with Acute Myocardial Infarction: a Pilot Study. AB - BACKGROUND: The aim of our study was to evaluate the clinical utility and prognostic significance of a cluster of 27 serum cytokines for risk stratification after myocardial infarction. MATERIALS AND METHODS: We enrolled 33 consecutive patients admitted to our institution for acute myocardial infarction and prospectively followed. We evaluated traditional cardiovascular risk factors and assayed, during the acute phase, 27 serum cytokines (IL-1, IL-1ra, IL-2, IL 4, IL-5, IL-6, IL -7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, EOTAXIN, FGF, G-CSF, GM-CSF, IFN-gamma, IP-10, MCP-1, MIP-1alpha, MIP-1beta, PDGF, RANTES, TNF-alpha, VEGF) potentially associated with cardiovascular risk. Patients were divided into two groups during follow-up according to the occurrence or absence of adverse cardiovascular events (recurrence of angina, re-infarction, death, need of new revascularization, occurrence of heart failure). We developed an additive risk score by assigning one point for each cytokine that had a value greater than the median value (range 0-27). Cytokines alone and the cytokines score were related to cardiovascular events. RESULTS: Patients with and without major adverse cardiovascular events (MACEs) at follow up had a homogenous distribution of the main cardiovascular risk factors; differences were detected only for sex and age. Patients who experienced MACE had a significantly different distribution of I troponin (p=0.036), IL-8 (p=0.006), IL-13 (p=0.06), IL-10 (p=0.02), IL-17 (p=0.015), IP-10 (p=0.02), MIP-1beta (p=0.05). At univariate analysis, IL -8 (p=0.046 OR 1.13), IL-10 (p=0.05 OR 1.14) and MIP-1beta (p=0.016, OR 1.02) were significantly associated with the occurrence of MACE. This association was not confirmed at multivariate analysis. At the analysis of variance, a higher score was significantly associated with the occurrence of adverse events at follow up (F=5.07, p=0.03). At ROC curve analysis, a score greater than 13 better predicted the occurrence of adverse events at follow-up (AUC 0.72, p=0.03, sensibility 59.1%, specificity 81.8%). CONCLUSIONS: In our study we did not identify a single inflammatory cytokine able to predict adverse events in a long term follow up, whereas the presence of more than 13 cytokines above the median value was useful for risk stratification. PMID- 26275689 TI - Influence of Vitamin C on Urine Dipstick Test Results. AB - BACKGROUND: Vitamin C is a strong reducing agent found at high levels in various foods, and it may influence the results of urine strip tests even at an ordinary consumption levels. After oral administration, we measured urine vitamin C levels using urine strips and evaluated whether vitamin C interfered with various test items. The utility of a urine strip with a vitamin C indicator was assessed. METHODS: Thirty-three healthy volunteers each ingested 1,000 mg of vitamin C. Their urine samples were tested for vitamin C using a URiSCAN 11 strip (YD Diagnostics, Korea) before and after administration of vitamin C. Standard materials were added to normal pooled urine to generate urine samples with various concentrations of the analytes tested (blood, bilirubin, nitrite, leukocytes, and glucose), and vitamin C was spiked to predetermined levels. These samples were then tested using two urine strips - URiSCAN and Chemstrip test strip (Roche Diagnostics, Germany) - to evaluate interference from vitamin C. In clinical samples with positive vitamin C results, microscopic and chemical analyses were also conducted to examine the differences. RESULTS: Thirteen urine samples from the 33 volunteers were positive for vitamin C before ingestion, and all subjects were positive after ingestion. Vitamin C spiking of urine demonstrated false-negative results at various concentrations. Of 159 specimens with positive results for vitamin C, 14 showed discrepant results after additional confirmatory tests. CONCLUSIONS: Vitamin C in urine can cause significant interference with urine strip tests. A urine strip with a vitamin C indicator is useful to reduce the risk of incorrect results in regard to disease states. PMID- 26275690 TI - Utility of Access Soluble Transferrin Receptor (sTfR) and sTfR/log Ferritin Index in Diagnosing Iron Deficiency Anemia. AB - The Access((r)) soluble transferrin receptor (sTfR) is considered the world's first automated chemiluminescence immunoassay. In this study, the diagnostic utility of this and other tests for serum iron were evaluated by studying their interrelationships with inflammation. A total of 367 patients with anemia (iron deficiency anemia [IDA], 157; anemia of chronic disease [ACD], 210) and 80 normal controls were subjected to a battery of diagnostic tests, including complete blood cell count, serum iron, total iron-binding capacity (TIBC), C-reactive protein (CRP), ferritin, sTfR, and hepcidin. The accuracy of test parameters was determined by the area under the receiver operating characteristic curve (AUC). Patients falling within the ferritin grey zone (10-100 ng/ml) were evaluated separately, given that such individuals are typically difficult to detect and manage in actual clinical practice. CRP was used to assess the correlation between the aforementioned markers of iron and inflammation. The single most accurate diagnostic test used to differentiate IDA from ACD was serum ferritin (AUC 0.989). However, sTfR assay outperformed other tests in the ferritin grey zone (AUC 0.931), and the sTfR/log ferritin index was the most reliable parameter in both scenarios (AUC 0.994 and 0.962, respectively). Ferritin, TIBC, and hepcidin showed the highest correlation with CRP, whereas sTfR displayed the lowest. The Access sTfR and sTfR/log ferritin index enabled highly accurate diagnosis of IDA in the ferritin grey zone. This is an easy-to-use automated chemiluminescence immunoassay, amenable to routine use in hospitals. PMID- 26275691 TI - Is the Use of Complete Blood Counts with Manual Differentials an Antiquated Method of Determining Neutrophil Composition in Newborns? AB - BACKGROUND: Automated complete blood counts (CBCs) provide imprecise measures of neonatal neutrophil composition due to the presence of nucleated red cells, which masquerade as white cells. Manual differentials (MDs) must be performed but can be flawed due to technician inexperience or limited cell counts. Our study evaluated whether flow cytometry could more accurately determine neutrophil composition in term newborns compared with adult controls. METHODS: Neutrophils were obtained by venipuncture in adults (n=10) and via cord blood from neonates delivered vaginally (n=21) or by primary cesarean section (n=17). Samples were processed by both flow cytometry and CBC with MD and results compared. Flow cytometry findings were verified using gene expression analysis of granule proteins. RESULTS: Immature-to-total neutrophil ratios were used to signify neutrophil composition. Flow cytometry was superior to manual differentials due to its ability to identify the earliest neutrophil forms. Significant differences between newborns and adults were determined using flow cytometry (0.12 versus 0.05; p=0.01), but not MDs (p=0.18). Neonates had similar findings irrespective of labor and method used. Verification of neutrophil maturity was completed using gene expression analysis of granule proteins. CONCLUSIONS: These results raise concerns about the accuracy of using CBCs with MDs to determine neutrophil composition. Further investigation of flow cytometry in clinical practice is warranted. PMID- 26275692 TI - Clinical and Forensic Diagnosis of Very Recent Heroin Intake by 6-acetylmorphine Immunoassay Test and LC-MS/MS Analysis in Urine and Blood. AB - AIM: The study evaluates the suitability of a specific immunoassay screening test for 6-acetylmorphine (6-AM) in the setting of suspected very recent heroin consumption for forensic and clinical purposes. MATERIAL AND METHOD: The EMIT(r) II Plus 6-AM immunoassay was applied in 65 cases that had already tested positive for morphine in urine or blood. Biological samples (n.65 urine and n.53 blood) were obtained from workplace drug tests (WDT n. 5), tests for driving under the influence of drugs (DUID n. 30), vehicle accidents (n. 10), overdoses (n. 12) and heroin-related deaths (n. 8) cases. The 6-AM screening assay results were confirmed with the LC-MS/MS analysis in relation to the cut-off set at 10 ng/mL for both urine and blood. RESULTS: Among the 65 urine samples (all morphine positive), 38 samples were 6-AM-positive and 27 were 6-AM-negative with 100% agreement between the positive/negative results of the two assays. Among the 53 blood samples (34 positive and 19 negative for the morphine), 16 were 6-AM positive and 37 were negative. Only one of the blood samples, positive for 6-AM by LC-MS/MS at 10.3 ng/mL, was negative by the immunoassay test. Based on the concordance between the results of the 6-AM immunoassay versus the LC-MS/MS, the sensitivity of the 6-AM assay was calculated as 100% and 95% for urine and blood respectively, with a specificity and accuracy of 100% for both biological samples. In addition, the study demonstrated that the 6-AM assay test, originally developed for urine, is also sufficiently sensitive to identify 6-AM in blood. Therefore, it could be applied in cases of vehicle accidents or overdose to distinguish rapidly between very recent heroin use and the intake of other opiates for therapeutic purposes. PMID- 26275693 TI - Effects of PRELI in Oxidative-Stressed HepG2 Cells. AB - Protein of relevant evolutionary and lymphoid interest (PRELI) is known for preventing apoptosis by mediating intramitochondrial transport of phosphatidic acid. However, the role of PRELI remains unclear. This study has demonstrated functions of PRELI through PRELI-knockdown in hepatocellular carcinoma (HepG2) cells exposed to oxidative stress by hydrogen peroxide. Results show that PRELI has three functions in HepG2 cells with regard to oxidative stress. First, PRELI affects expressional regulation of SOD-1 and caspase-3 genes in HepG2 cells. PRELI knockdown HepG2 cells have shown up-regulation of caspase-3 and down regulation of SOD-1. Second, PRELI suppresses mitochondrial apoptosis in HepG2 cells. Fluorescence intensity related to mitochondrial apoptosis in PRELI knockdown HepG2 cells increased more than two-fold compared to normal HepG2 cells. Third, PRELI suppresses senescence of HepG2 cells with oxidative stress. PRELI knockdown HepG2 cells showed higher levels of senescence than normal HepG2 cells. These results suggest that PRELI is a crucial protein in the suppression of apoptosis in HepG2 cells in response to oxidative stress. PMID- 26275694 TI - Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model. AB - BACKGROUND: To investigate the effects of AOD9604 intra-articular injections with or without hyaluronic acid (HA) in a collagenase-induced knee osteoarthritis (OA) rabbit model. DESIGN: Mature New Zealand white rabbits (n=32) were randomly administered 2 mg collagenase type II twice in each knee joint. Weekly injections of 0.6 mL saline (Group 1), 6 mg HA (Group 2), 0.25 mg AOD9604 (Group 3), and 0.25 mg AOD9604 with 6 mg HA (Group 4) were administered for 4-7 weeks after the first intra-articular collagenase injection. The degree of cartilage degeneration was assessed using morphological and histopathological findings, and the degree of lameness was observed at 8 weeks after the first collagenase injection. RESULTS: Mean gross morphological and histopathological scores were significantly higher in Group 1 than in Groups 2, 3, and 4, and the scores were significantly lower in Group 4 than in Groups 2 and 3. The lameness period in Group 4 was significantly shorter than those in Groups 1, 2, and 3. The lameness period in Group 1 was significantly longer than those in Groups 2 and 3. CONCLUSION: Intra articular AOD9604 injections using ultrasound guidance enhanced cartilage regeneration, and combined AOD9604 and HA injections were more effective than HA or AOD9604 injections alone in the collagenase-induced knee OA rabbit model. PMID- 26275695 TI - Association between SNP309 and del1518 Polymorphism in MDM2 Homologue and Esophageal Squamous Cell Carcinoma Risk in Chinese Population of Shandong Province. AB - BACKGROUND: Murine double-minute 2 homologue (MDM2) is a key negative regulator of p53. Polymorphisms in the promoter region were shown to alter the gene activity and/or function, suggesting a possible role in carcinogenesis. OBJECTIVE AND METHOD: The current study aims to investigate the association of SNP309 and del1518 polymorphisms as well as their haplotypes in MDM2 with the risk of esophageal squamous cell carcinoma (ESCC) in the Chinese population. This study included 132 patients with ESCC and 132 age-matched healthy controls. Genotyping was performed by RFLP-PCR analysis. Genotypic and allelic frequencies were then evaluated. Statistical analyses were performed using SPSS software. RESULTS: The frequency of the GG genotype of SNP309 was 10.61% for controls and 18.94% for cases. A significant difference was detected between the two groups (odds ratio [OR] 2.27; 95% confidence interval [CI]: 1.04-4.97; p=0.04). The linkage disequilibrium (LD) existed between SNP309 and del 1518(D'=0.68) in MDM2. Compared with "T-" haplotype, the "G+" haplotype can significantly increase the risk of ESCC (OR=1.65; 95% CI:1.09-2.51; p=0.02). CONCLUSIONS: MDM2 SNP309 polymorphisms and SNP309G-del1518+ haplotype may significantly contribute to genetic susceptibility to ESCC in the Chinese population. PMID- 26275696 TI - The Usage of Separating Gel Vacuum Tube with Different IgG Concentration. AB - BACKGROUND: Observing serum IgG concentration on the distribution of serum, blood cells, and separation gel after centrifugation in different separation gel vacuum tubes. METHODS: 3 mL venous blood was collected in each of two separation gel procoagulant vacuum tubes: BD Vacutainer SST II(3.5ml, 75*13 mm) and BD Vacutainer SST(5ml, 100*13 mm). After complete solidifaction, both tubes were centrifuged at 2000g for 10 minutes. The distribution of serum, blood cells, and separation gel in the vacuum tube was observed. The immunoglobulin concentration was detected using the special protein analyzer Siemens BNII. RESULTS: 1. In the group of BD Vacutainer SST II where the IgG concentration exceeded 50g/L but less than 122g/L: The serum was located below the separation gel and was distributed in three layers: separation gel, serum, and blood cells. 2. In the group of BD Vacutainer SST where the IgG concentration exceeded 50g/L but less than 122g/L: The serum was located above the separating gel, and was distributed in three layers: serum, separation gel, and blood cells. 3. Increases in IgA and IgM serum concentration did not cause the separation gel inversion. CONCLUSIONS: Increases in serum IgG were positively correlated with the concentration of total protein. The rising of serum IgG caused the floating of separation gel after centrifugation. The BD Vacutainer SST was more suitable for clinical blood sample collection. PMID- 26275697 TI - Inflammatory Fibroid Polyp of the Ileocecal Valve: Case Report, Review, and Recent Advances. AB - We report a case of a 72-year-old woman who underwent a right hemicolectomy for a near-obstructing mass in the ileocecal valve. The histologic diagnosis was inflammatory fibroid polyp (IFP). IFPs are rare mesenchymal lesions that can arise throughout the gastrointestinal tract. Originally considered reactive or inflammatory, recent studies report activating mutations of platelet derived growth factor receptor-alpha (PDGFRA) in IFPs, suggesting that these may in fact be neoplastic. Nonetheless, these are benign lesions cured by local excision and typically do not recur or metastasize. Our patient also had no evidence of local recurrence one year after the surgery. Hence, the clinical importance lies in distinguishing these lesions from other benign and malignant mesenchymal proliferative lesions both on a biopsy and resection specimen. We review the literature on clinicopathologic features, immunohistochemical profile, pathogenesis, recent advances, differential diagnosis, prognosis, and treatment of these uncommon lesions. PMID- 26275698 TI - A Novel de novo Mutation in the G6PD Gene in a Korean Boy with Glucose-6 phosphate Dehydrogenase Deficiency: Case Report. AB - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive hemolytic anemia caused by a mutation in the G6PD gene on Xq28. Herein, we describe a Korean boy with G6PD deficiency resulting from a novel mutation in G6PD. A 20-month-old boy with hemolytic anemia was referred for molecular diagnosis. He had no relevant family history. The G6PD activity was severely decreased at 0.2 U/g Hb (severe deficiency). Direct sequencing analyses on the G6PD gene revealed that he was hemizygous for a novel missense variant, c.1187C>G (p.Pro396Arg), in exon 10 of G6PD. Family study involving his parents revealed the de novo occurrence of the mutation. This is the first report of genetically confirmed G6PD deficiency in Korea. PMID- 26275699 TI - A Case of Diabetic Mellitus Foot Infection by a Newly Reported Neisseria Skkuensis: Case Report. AB - In pus and wound samples collected from the right second toe of a 61-year-old woman with diabetes mellitus (DM), gram-negative diplococci bacterium was observed. However, the bacterium could not be identified by conventional microbiological methods and mass spectrometry. In the partial 16S rRNA gene sequence analysis, the bacterium showed a 100% identity match with GenBank sequence FJ0763637.1 (Neisseria skkuensis). N. skkuensis, SMC-A9199 strain, was reported as a novel species in 2010 based on its phenotypic characteristics and the 16S rRNA gene sequence, which was isolated from the blood and wound pus of a DM patient with a foot ulcer. The second reported N. skkuensis was identified from the blood cultures of a patient with endocarditis. To the best of our knowledge, this is only the third report of N. skkuensis. PMID- 26275700 TI - Letter to Editor: Chemokine Network Involved in Inflammatory Skin Diseases. AB - Chemokines are low-molecular-weight chemotactic proteins that regulate the trafficking of leukocytes to inflammatory sites and may recruit inflammatory cells to the epidermis. Chemokines are produced by many immune cells such as macrophages, mast cells, T lymphocytes and others, in response to pro inflammatory stimuli including IL-1, TNF and LPS. Immune cells which participate in inflammatory skin disorders, upon activation express several adhesive and immune receptors such as P-selectin, CD40 ligand, and Toll-like receptors on their surface, and generate cytokines/chemokines. Chemokines have crucial functions in inflammation, and cell dysregulations and they are recognized as potentially important in diverse skin pathologies associated with the severity of disease. Injection of chemokines in the rat skin provoke the recruitment of inflammatory cells, release of cytokines, and activation of transcription of histidine decarboxylase (HDC), the enzyme responsible for the generation of histamine from histidine, which may cause fatal anaphylactic shock. Therefore, the use of anti-chemokines for inflammatory skin diseases remains a promising therapeutic approach. However, the complete role of chemokines in inflammatory skin diseases remains to be further studied. Here we report the relationship between chemokines and skin inflammation. PMID- 26275701 TI - Letter to the Editor: A Novel Mutation in the CREBBP Gene of a Korean Girl with Rubinstein-Taybi syndrome. AB - Rubinstein-Taybi syndrome (RTS) is a rare congenital disorder characterized by broad thumbs and halluces, dysmorphic facial features, mental retardation, and short stature. Mutations in the cAMP-response element binding protein-BP (CREBBP) gene (50-60% of cases) and E1A-binding protein (EP300, 3%) are known genetic causes in affected individuals. Here, we describe a genetically confirmed Korean RTS patient with atypical features, including Hirschsprung disease and growth hormone deficiency. Mutational analysis revealed a novel heterozygous frameshift mutation, c.2064_2077del14 (p.Gly689Cysfs*32) in the CREBBP gene. PMID- 26275702 TI - A NR3C2 haplotype increases the risk of alcoholism in schizophrenic patients in Han Chinese population. PMID- 26275703 TI - Abnormal brainstem auditory response in young females with ADHD. AB - Studies have shown that the auditory brainstem response (ABR) is often affected in neurodevelopmental disorders. The aim of this study is to investigate possible differences in ABR between young females with ADHD compared to control subjects. This study focuses on young females, age 7-17 with ADHD, comparing the ABR of 43 young females with ADHD to 21 age- and gender-matched control subjects. Young females with ADHD have a significantly different ABR in a region between cochlear nucleus and superior olivary complex as well as in the thalamic region compared to control subjects. These data indicate specific differences in ABR between girls with ADHD compared to female controls. PMID- 26275704 TI - TNF-related weak inducer of apoptosis (TWEAK) levels in schizophrenia. AB - Members of tumor necrosis factor (TNF) superfamily have roles in many biological events and pathogenesis of central nervous system (CNS) diseases. A relatively recently found member of this family, TNF-related weak inducer of apoptosis (TWEAK) have importance both in development of pathological CNS processes and as a target for the treatment of these diseases. The aim of this study was to investigate whether TWEAK's plasma levels are different in patients with schizophrenia. For this purpose plasma TWEAK levels of 44 patients diagnosed with schizophrenia and control group of 40 healthy individuals were compared. Although numerical difference was found between TWEAK levels of patients and controls it was not statistically significant. When we tested for female and male patients and controls seperately, TWEAK levels of male patients were significantly lower than male controls. As far as we know this is the first study that investigates levels of TWEAK in patients with schizophrenia. Although we did not find statistically significant results in our study, we believe that difference could be found in future studies with higher number of subjects. Researches with non studied TNF superfamily members like TWEAK and TNF-related apoptosis-inducing ligand (TRAIL) could contribute to the understanding of immune-cytokine related hypotheses of schizophrenia. PMID- 26275705 TI - Highly efficacious cognitive-coping therapy for overt or covert compulsions. AB - Pharmacotherapy and cognitive-behavioral therapy (CBT) present limitations when they are used to treat obsessive-compulsive disorder (OCD), a severe and debilitating psychiatric disorder. To search for more efficacious treatment, we investigated the effects of pharmacotherapy plus cognitive-coping therapy (pCCT) on adult OCD patients with overt or covert compulsions. Two hundred and fifteen OCD patients were randomized into pharmacotherapy plus psychological support (PPS, n=107) and pCCT (n=108). The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was used to measure severity of symptoms in the OCD patients. The Y-BOCS scores were significantly lower in pCCT than in PPS in both acute term (<3 months) and long-term follow-up. In pCCT, severity of symptoms was not different between those with covert compulsions and those with overt compulsions, but was significantly reduced at any post-treatment time-point. Y-BOCS scores in the two subtype compulsions were significantly lower in pCCT than in PPS at any post treatpost-treatment time-point. Compared with PPS, effect size, response rate and remission rate were significantly higher in pCCT. Our findings corroborated with the hypothesis that pCCT could efficaciously treat OCD with overt compulsions or covert compulsion, suggesting that pCCT might be a potential option for adult OCD. PMID- 26275706 TI - Screening tools for psychiatry disorders in cancer setting: Caution when using. AB - This study evaluated sensitivity/specificity of self-report instruments for the screening of psychiatric disorders/symptoms in cancer outpatients like: current/past major depression, dysthymia, alcohol abuse and dependence, tobacco abuse and dependence, panic disorder, social anxiety disorder, generalized anxiety disorder, obsessive compulsive disorder, posttraumatic stress disorder, phobias, current mania, delusion and hallucination. First, 1384 patients responded to several self-assessment instruments. Then, 400 patients, were then interviewed by telephone to confirm the presence/absence of psychiatric diagnosis. The ROC analyses showed moderate/excellent specificity (Patient Health Questionnaire-4 (PHQ-4)=0.75-0.88, Generalized Anxiety Disorder (GAD-7)=0.77, Fast Alcohol Screening Test (FAST)=0.83-0.86, Fagerstrom Test for Nicotine Dependence (FTND)=0.72, Brief version of the Patient Health Questionnaire-Panic Disorder Module (Brief-PD)=0.75, and Self Reporting Questionnaire - psychosis items=(0.68-0.91) but low sensitivity (PHQ-4=0.53-0.54, GAD-7=0.52, FAST=0.48 0.58, FTND=0.97, and Brief-PD=0.66)). These results suggest that sensitivity indicators should be used with caution in the cancer clinical setting. PMID- 26275707 TI - Magnetic iron oxide nanoparticles: Recent trends in design and synthesis of magnetoresponsive nanosystems. AB - Recent developments in nanotechnology and application of magnetic nanoparticles, in particular in magnetic iron oxide nanosystems, offer exciting possibilities for nanomedicine. Facile and precise synthesis procedures, high magnetic response, tunable morphologies and multiple bio-functionalities of single- and multi-core magnetic particles designed for nanomedicine applications are thoroughly appraised. This review focuses on the structural and magnetic characterization of the cores, the synthesis of single- and multicore iron oxide NPs, especially the design of the latter, as well as their protection, stabilization and functionalization by desired coating in order to protect against the corrosion of core, to prevent non-specific protein adsorption and particle aggregation in biological media, and to provide binding sites for targeting and therapeutic agents. PMID- 26275708 TI - Targeted activation of endothelin-1 exacerbates hypoxia-induced pulmonary hypertension. AB - Pulmonary arterial hypertension (PAH) is a fatal disease that eventually results in right heart failure and death. Current pharmacologic therapies for PAH are limited, and there are no drugs that could completely cure PAH. Enhanced activity of endothelin system has been implicated in PAH severity and endothelin receptor antagonists have been used clinically to treat PAH. However, there is limited experimental evidence on the direct role of enhanced endothelin system activity in PAH. Here, we investigated the correlation between endothelin-1 (ET-1) and PAH using ET-1 transgenic (ETTG) mice. Exposure to chronic hypoxia increased right ventricular pressure and pulmonary arterial wall thickness in ETTG mice compared to those in wild type mice. Of note, ETTG mice exhibited modest but significant increase in right ventricular pressure and vessel wall thickness relative to wild type mice even under normoxic conditions. To induce severe PAH, we administered SU5416, a vascular endothelial growth factor receptor inhibitor, combined with exposure to chronic hypoxia. Treatment with SU5416 modestly aggravated hypoxia induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary arterial vessel wall thickening in ETTG mice in association with increased interleukin-6 expression in blood vessels. However, there was no sign of obliterative endothelial cell proliferation and plexiform lesion formation in the lungs. These results demonstrated that enhanced endothelin system activity could be a causative factor in the development of PAH and provided rationale for the inhibition of endothelin system to treat PAH. PMID- 26275709 TI - Outcomes in consecutive hospitalized UK patients with bacteraemia or fungaemia caused by medical devices and procedures. AB - BACKGROUND: There is a lack of outcome data on hospitalized patients with bacteraemia or fungaemia caused by medical devices or procedures. AIM: To determine the association between death and bacteraemia or fungaemia caused by medical devices and procedures. METHODS: From December 2012 to November 2013, demographic, clinical, and microbiological data were collected on consecutive inpatients with bacteraemia or fungaemia. Multivariate analysis, using generalized estimating equations, was used to define the association. FINDINGS: A total of 594 bacteraemic or fungaemic episodes occurred in 500 patients. Among patients with episodes caused by medical devices or procedures, 7-day and 30-day mortality were 7/167 [4.2%; 95% confidence interval (CI): 1.7-8.4] and 12/167 (7.2%; CI: 3.8-12.2) respectively. After adjustment, the association between death and bacteraemic or fungaemic episodes related to medical devices and procedures was non-significant as 7- and 30-day mortality odds ratios (OR) were 2.86 (95% CI: 0.80-10.12) and 1.72 (95% CI: 0.71-4.16) respectively. The difference between 30-day mortality associated with Escherichia coli and Staphylococcus aureus bacteraemia demonstrated a trend towards significance [6/47 (12.8%; CI: 4.8-25.7) vs 0/24; P = 0.067]. Thirty-day mortality associated with bacteraemia or fungaemia in patients with urinary catheter infections (often E. coli-associated) was significantly higher than intravascular device-associated infections (often S. aureus-associated) [4/51 (7.8%; 95% CI: 2.2-18.8) vs 1/62 (1.6%; 95% CI: 0.0-8.7); P = 0.028]. CONCLUSION: Special attention is required to prevent medical device- or procedure-related bacteraemia caused by E. coli. Greater attention should be placed on preventing infections caused by urinary catheters. PMID- 26275710 TI - Revision of the opinion on peanut oil - Sensitisation only. PMID- 26275711 TI - Hypertension in children with end-stage renal disease. AB - This review summarizes current data on the epidemiology, pathophysiology, and treatment of hypertension (HTN) in children with end-stage renal disease (ESRD). Worldwide prevalence of ESRD ranges from 5.0 to 84.4 per million age-related population. HTN is present in 27-79% of children with ESRD, depending on the modality of renal replacement therapy and the exact definition of hypertension. Ambulatory BP monitoring has been recommended for the detection of HTN and evaluation of treatment effectiveness. HTN in dialyzed patients is mostly related to hypervolemia, sodium overload, activation of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system, impaired nitric oxide synthesis, reduced vitamin D levels, and effects of microRNA. In children undergoing chronic dialysis therapy, important factors include optimization of renal replacement therapy and preservation of residual renal function, allowing reduction of volume and sodium-overload, along with appropriate drug treatment, particularly with calcium channel blockers, RAAS inhibitors, and loop diuretics. PMID- 26275712 TI - The calibration of cellphone camera-based colorimetric sensor array and its application in the determination of glucose in urine. AB - In this work, a novel approach that can calibrate the colors obtained with a cellphone camera was proposed for the colorimetric sensor array. The variations of ambient light conditions, imaging positions and even cellphone brands could all be compensated via taking the black and white backgrounds of the sensor array as references, thereby yielding accurate measurements. The proposed calibration approach was successfully applied to the detection of glucose in urine by a colorimetric sensor array. Snapshots of the glucose sensor array by a cellphone camera were calibrated by the proposed compensation method and the urine samples at different glucose concentrations were well discriminated with no confusion after a hierarchical clustering analysis. PMID- 26275713 TI - DNA-stabilized bimetallic nanozyme and its application on colorimetric assay of biothiols. AB - This paper reports a facile synthesis of bimetallic AuxPty nanozyme using C-rich oligonucleotide as the nucleation template, with high peroxidase-like activity and thiophilicity associated with the ratio of x:y. The efficient Au2Pt1 nanozyme possesses highly peroxidase mimicking activity with the Km value of 0.088 mM toward 3,3',5,5'-tetramethylbenzidine and 196 mM toward hydrogen peroxide. It is the first report to explore colorimetric assays for biothiols with high sensitivity and selectivity against non-thiol-containing amino acids, on the basis of thiol-induced inhibition of peroxidase-like activities of metal nanoparticles. By using Au2Pt1 nanozyme, the limit of detection (LOD) is 3.5 nM for cysteine and 1.6 nM for homocysteine. This DNA-stabilized bimetallic AuxPty nanozyme shows a promising application in quantitative detection of biothiols in biological fluids. PMID- 26275714 TI - Benefits for elders with vulnerable health from the Chronic Disease Self management Program (CDSMP) at short and longer term. AB - BACKGROUND: When health declines, older persons may benefit from an intervention program that strengthens their self-management and empowers them to keep in control of their own body and life. Therefore we conducted a Randomized Controlled Trial using the Chronic Disease Self-Management Program (CDSMP) in a sample of 169 older persons in frail health and in need of elderly care. METHODS: We assessed psychological coping resources and wellbeing, pre- and posttreatment and at 6-month follow-up, and investigated whether specific subgroups would benefit in particular from the intervention. RESULTS: The CDSMP appeared effective with respect to sense of mastery but only in the lower educated participants (p < .05). Furthermore, the intervention stabilized valuation of life in participants, whereas in the controls valuation of life decreased. The high appreciation score and low drop-out are indicative for the applicability of the CDSMP for this specific target group. CONCLUSIONS: We recommend integration of the ingredients of the program into the daily healthcare practice of professionals working with vulnerable older persons. This would involve professional guidance starting from interpersonal equality and emphasising a persons possibilities given their physical or cognitive limitations. This will help older vulnerable persons to focus on their own attainable goals and to experience being successful. TRIAL REGISTRATION: The trial was registered in the Dutch Trial Register as NTR 1173 at 08-03-2008; 'Is selfmanagement benefical for well-being of average older persons?' http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1173. PMID- 26275716 TI - The impact of migration on the health status of Iranians: an integrative literature review. AB - BACKGROUND: Immigration, both voluntary and forced, is driven by social, political and economic factors. Accordingly, some discussions and debates have emerged in recent years about the impact of migration on the health status of migrants. The aim of this review was to identify the impact of migration on the health status of Iranian immigrants and present a conceptual framework to facilitate the design and delivery of services and supports for this particular immigrant group. METHODS: Data for this integrative review were collected from Medline, PsycINFO, Scopus, ProQuest, Academic Search Complete, CINAHL, and Google Scholar search engine. The database search was limited to peer-reviewed literature, published in English, between 1980 and 2013. RESULTS: Twenty six articles were included in the review. Analysis revealed several factors influencing the mental health of immigrants, including language insufficiency; unemployment; sense of discrimination; cultural shock; lack of social support; lack of information about health care services; and intimate partner violence. CONCLUSION: Findings of this review have contributed to development of a conceptual framework that delineates the impact of migration on Iranian immigrants' health. This conceptualization may also help in addressing the needs of other vulnerable groups during the transition phase of migration. PMID- 26275717 TI - Increasing venoarterial extracorporeal membrane oxygenation flow negatively affects left ventricular performance in a porcine model of cardiogenic shock. AB - BACKGROUND: The aim of this study was to assess the relationship between extracorporeal blood flow (EBF) and left ventricular (LV) performance during venoarterial extracorporeal membrane oxygenation (VA ECMO) therapy. METHODS: Five swine (body weight 45 kg) underwent VA ECMO implantation under general anesthesia and artificial ventilation. Subsequently, acute cardiogenic shock with signs of tissue hypoxia was induced. Hemodynamic and cardiac performance parameters were then measured at different levels of EBF (ranging from 1 to 5 L/min) using arterial and venous catheters, a pulmonary artery catheter and a pressure-volume loop catheter introduced into the left ventricle. RESULTS: Myocardial hypoxia resulted in a decline in mean (+/-SEM) cardiac output to 2.8 +/- 0.3 L/min and systolic blood pressure (SBP) to 60 +/- 7 mmHg. With an increase in EBF from 1 to 5 L/min, SBP increased to 97 +/- 8 mmHg (P < 0.001); however, increasing EBF from 1 to 5 L/min significantly negatively influences several cardiac performance parameters: cardiac output decreased form 2.8 +/- 0.3 L/min to 1.86 +/- 0.53 L/min (P < 0.001), LV end-systolic volume increased from 64 +/- 11 mL to 83 +/- 14 mL (P < 0.001), LV stroke volume decreased from 48 +/- 9 mL to 40 +/- 8 mL (P = 0.045), LV ejection fraction decreased from 43 +/- 3 % to 32 +/- 3 % (P < 0.001) and stroke work increased from 2096 +/- 342 mmHg mL to 3031 +/- 404 mmHg mL (P < 0.001). LV end-diastolic pressure and volume were not significantly affected. CONCLUSIONS: The results of the present study indicate that higher levels of VA ECMO blood flow in cardiogenic shock may negatively affect LV function. Therefore, it appears that to mitigate negative effects on LV function, optimal VA ECMO blood flow should be set as low as possible to allow adequate tissue perfusion. PMID- 26275715 TI - A comprehensive evaluation of interaction between genetic variants and use of menopausal hormone therapy on mammographic density. AB - INTRODUCTION: Mammographic density is an established breast cancer risk factor with a strong genetic component and can be increased in women using menopausal hormone therapy (MHT). Here, we aimed to identify genetic variants that may modify the association between MHT use and mammographic density. METHODS: The study comprised 6,298 postmenopausal women from the Mayo Mammography Health Study and nine studies included in the Breast Cancer Association Consortium. We selected for evaluation 1327 single nucleotide polymorphisms (SNPs) showing the lowest P-values for interaction (P int) in a meta-analysis of genome-wide gene environment interaction studies with MHT use on risk of breast cancer, 2541 SNPs in candidate genes (AKR1C4, CYP1A1-CYP1A2, CYP1B1, ESR2, PPARG, PRL, SULT1A1 SULT1A2 and TNF) and ten SNPs (AREG-rs10034692, PRDM6-rs186749, ESR1-rs12665607, ZNF365-rs10995190, 8p11.23-rs7816345, LSP1-rs3817198, IGF1-rs703556, 12q24 rs1265507, TMEM184B-rs7289126, and SGSM3-rs17001868) associated with mammographic density in genome-wide studies. We used multiple linear regression models adjusted for potential confounders to evaluate interactions between SNPs and current use of MHT on mammographic density. RESULTS: No significant interactions were identified after adjustment for multiple testing. The strongest SNP-MHT interaction (unadjusted P int <0.0004) was observed with rs9358531 6.5kb 5' of PRL. Furthermore, three SNPs in PLCG2 that had previously been shown to modify the association of MHT use with breast cancer risk were found to modify also the association of MHT use with mammographic density (unadjusted P int <0.002), but solely among cases (unadjusted P int SNP*MHT*case-status <0.02). CONCLUSIONS: The study identified potential interactions on mammographic density between current use of MHT and SNPs near PRL and in PLCG2, which require confirmation. Given the moderate size of the interactions observed, larger studies are needed to identify genetic modifiers of the association of MHT use with mammographic density. PMID- 26275718 TI - Counselling versus low-intensity cognitive behavioural therapy for persistent sub threshold and mild depression (CLICD): a pilot/feasibility randomised controlled trial. AB - BACKGROUND: Persistent depressive symptoms below the threshold criteria for major depression represent a chronic condition with high risk of progression to a diagnosis of major depression. The evidence base for psychological treatments such as Person-Centred Counselling and Low-Intensity Cognitive Behavioural Therapy for sub-threshold depressive symptoms and mild depression is limited, particularly for longer-term outcomes. METHODS: This study aimed to test the feasibility of delivering a randomised controlled trial into the clinical and cost effectiveness of Low-Intensity Cognitive Behavioural Therapy versus Person Centred Counselling for patients with persistent sub-threshold depressive symptoms and mild depression. The primary outcome measures for this pilot/feasibility trial were recruitment, adherence and retention rates at six months from baseline. An important secondary outcome measure was recovery from, or prevention of, depression at six months assessed via a structured clinical interview by an independent assessor blind to the participant's treatment condition. Thirty-six patients were recruited in five general practices and were randomised to either eight weekly sessions of person-centred counselling each lasting up to an hour, or up to eight weeks of cognitive-behavioural self-help resources with guided telephone support sessions lasting 20-30 minutes each. RESULTS: Recruitment rate in relation to the number of patients approached at the general practices was 1.8 %. Patients attended an average of 5.5 sessions in both interventions. Retention rate for the 6-month follow-up assessments was 72.2 %. Of participants assessed at six months, 71.4 % of participants with a diagnosis of mild depression at baseline had recovered, while 66.7 % with a diagnosis of persistent subthreshold depression at baseline had not developed major depression. There were no significant differences between treatment groups for both recovery and prevention of depression at six months or on any of the outcome measures. CONCLUSIONS: It is feasible to recruit participants and successfully deliver both interventions in a primary care setting to patients with subthreshold and mild depression; however recruiting requires significant input at the general practices. The evidence from this study suggests that short-term Person-Centred Counselling and Low-Intensity Cognitive Behaviour Therapy are potentially effective and their effectiveness should be evaluated in a larger randomised controlled study which includes a health economic evaluation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN60972025 . PMID- 26275719 TI - An untargeted metabolomics-driven approach based on LC-TOF/MS and LC-MS/MS for the screening of xenobiotics and metabolites of Zhi-Zi-Da-Huang decoction in rat plasma. AB - Zhi-Zi-Da-Huang decoction (ZZDHD), a typical traditional Chinese medicine prescription, is widely used in clinical practice for the treatment of alcoholic liver disease. However, due to lack of holistic metabolic research, the active ingredients of ZZDHD have not been fully elucidated. It entails a huge obstacle for the quality evaluation, pharmacokinetic studies and clinical-safe medication administration of ZZDHD. In this work, an untargeted metabolomics-driven approach was proposed to rapidly screen and characterize xenobiotics and related metabolites in vivo conducted by LC-TOF/MS and LC-QqQ/MS. The tR-m/z pairs which were present in the ZZDHD-dosed group and absent in the control group could be clearly displayed by XCMS Online platform combined with supervised orthogonal partial least squares discriminant analysis. Among them, a total of 61 ZZDHD related xenobiotics and metabolites including 34 prototype components and 27 metabolites were rapidly identified or tentatively characterized in rat plasma. The results indicated that iridoid glycosides and monoterpenoids from Gardenia jasminoides Ellis, flavonoid glycosides from Citrus aurantium L., as well as anthraquinones from Rheum palmatum L. were the main absorbed chemical components of ZZDHD. Hydrolysis, glucuronidation and sulfation were the main metabolic pathways of ZZDHD in vivo. The present study provided a solid basis for further revealing the relationship between the xenobiotic metabolome and pharmacological activity of ZZDHD. In addition, the application of untargeted metabolomics-driven approach offers a fresh insight for rapid screening and identifying xenobiotics and metabolites of ZZDHD and other multiherb prescription. PMID- 26275720 TI - Identification of a new tadalafil analogue in an adulterated dietary supplement: trans-Bisprehomotadalafil. AB - A new tadalafil analogue was identified along with homotadalafil during routine screening of an adulterated dietary supplement using HPLC-DAD. The UV spectrum of this analogue was almost identical with that of tadalafil. This compound was isolated from the supplement by using semi-preparative HPLC and its structure was subsequently elucidated by performing Q-TOF/MS/MS and NMR spectroscopic experiments. The spectral data indicate that this tadalafil analogue is a dimeric compound that consists of an ethylamino group and two pretadalafil moieties. NOE experiments and comparison with (1)H NMR spectra of tadalafil and trans-tadalafil suggested the trans-relationship between the substituents on piperidine rings in the pretadalafil moieties. PMID- 26275721 TI - Intentions of Muslim Arab women in Israel to attend prenatal classes. AB - BACKGROUND: Prenatal education has many benefits to both mother and child. In Israel, prenatal classes are offered to pregnant women in their third trimester from all cultures and sectors. However, Israeli Muslim Arab women often do not attend these classes. AIM: To explore factors influencing the intention of Muslim Arab women in Israel to attend prenatal classes, using the Theory of Planned Behavior. METHODS: The study was a cross-sectional quantitative correlational design. A convenience sample consisting of 200 Arab Muslim women completed a questionnaire based on the literature review and the theoretical model. FINDINGS: The research findings indicate that women's intention to attend prenatal classes increases with more positive beliefs and attitudes toward prenatal education, greater subjective social pressure to attend classes, and with higher perceived control of attending such classes. The higher a woman's age and level of education, the greater her intention to attend classes. This study shows that the spouse is the most significant factor influencing women's decisions on this matter. CONCLUSION: In order to raise the intentions of Muslim Arab women in Israel to attend prenatal classes, policy makers must design programs to increase the awareness of prenatal education among both women and men in the Muslim Arab sector, emphasizing its benefits for mothers, infants, and families as a whole. Classes should reflect the uniqueness of Israeli Muslim Arab culture and combine traditional and modern outlooks. PMID- 26275722 TI - A Test of Social Cognitive Theory to Explain Men's Physical Activity During a Gender-Tailored Weight Loss Program. AB - Physical inactivity is a leading contributor to the burden of disease in men. Social-cognitive theories may improve physical activity (PA) interventions by identifying which variables to target to maximize intervention impact. This study tested the utility of Bandura's social cognitive theory (SCT) to explain men's PA during a 3-month weight loss program. Participants were 204 overweight/obese men (M [SD] age = 46.6 [11.3] years; body mass index = 33.1 [3.5] kg/m2). A longitudinal, latent variable structural equation model tested the associations between SCT constructs (i.e., self-efficacy, outcome expectations, intention, and social support) and self-reported moderate-to-vigorous PA (MVPA) and examined the total PA variance explained by SCT. After controlling for Time 1 cognitions and behavior, the model fit the data well (chi2 = 73.9, degrees of freedom = 39, p < .001; normed chi2 = 1.9; comparative fit index = 0.96; standardized root mean residual = 0.059) and explained 65% of the variance in MVPA at Time 2. At Time 2, self-efficacy demonstrated the largest direct and total effects on MVPA (betadirect = .45, p < .001; betatotal = .67, p = .002). A small-to-medium effect was observed from intention to MVPA, but not from outcome expectations or social support. This study provides some evidence supporting the tenets of SCT when examining PA behavior in overweight and obese men. Future PA and weight loss interventions for men may benefit by targeting self-efficacy and intention, but the utility of targeting social support and outcome expectations requires further examination. PMID- 26275724 TI - Magnetic resonance cholangiography: Current and future perspectives. AB - Magnetic resonance cholangiography (MRC) has become the standard of reference for imaging of the biliary ducts. The use of three-dimensional (3D) sequences has resulted in improved spatial resolution with virtually isotropic voxel and improved signal/noise ratio. In addition to MRC images, 3D fat suppressed T1 weighted MR images should be systematically obtained to search for intrahepatic calculi. MRC plays a major role in the diagnosis of cholangiocarcinoma and assessment of its resectability. With modern MR systems the performance of MR is basically the same that of CT for evaluation of arterial and portal vein extent. MRC is a key imaging modality for the diagnosis of primary sclerosing cholangitis. Different imaging patterns may be observed including multifocal intra- and extrahepatic strictures alternating with slightly dilated ducts. Focal signal abnormality of the liver parenchyma and focal parenchymal atrophy represent the consequences of biliary duct obstruction on liver parenchyma. Diagnosis of biliary lithiasis is performed by combination of MRC and T1-weighted MR imaging. MRC can be performed for the diagnosis of secondary cholangitis including ascending cholangitis, ischemic cholangitis and IgG4-related sclerosing cholangitis. Hepatobiliary contrast agents could be used for demonstrating the site of biliary duct leakage after surgery and for functional imaging. MR imaging can also be used to determine the prognosis of PSC. The inherent limitations of MRC of bile ducts are still the suboptimal spatial resolution for evaluation of distal intrahepatic biliary ducts. PMID- 26275723 TI - Enhanced cough reflex in a model of bleomycin-induced lung fibrosis in guinea pigs. AB - Fibrotic lung diseases, such as idiopathic pulmonary fibrosis, are associated with spontaneous dry cough and hypersensitivity to tussive agents. Understanding the pathophysiology driving enhanced cough may help us to define better therapies for patients. We hypothesized that lung fibrosis induced by intratracheal bleomycin would exacerbate the cough reflex induced by tussive agents in guinea pigs. Disease progression in the lungs was characterized at days 1, 7, 14, 21 and 28 after bleomycin administration. Inflammatory and fibrotic markers, as well as neurotrophin levels, were assessed in bronchoalveolar lavage fluid and/or lung tissue. Cough sensitivity to citric acid, capsaicin and allylisothiocyanate was evaluated in conscious animals at days 14 and 21 after bleomycin administration. Pulmonary lesions evolved from an early inflammatory phase (from day 1 to day 7) to a fibrotic stage (between days 14 and 28). Fibrosis was related to increased levels of matrix metalloproteinase-2 in bronchoalveolar lavage fluid (day 21: saline, 0.26 ng/ml; bleomycin, 0.49 ng/ml). At day 14, we also observed increased cough reflexes to citric acid (163%), capsaicin (125%) and allylisothiocyanate (178%). Cough exacerbation persisted, but at a lower extent, by day 21 for capsaicin (100%) and allylisothiocyanate (54%). Moreover, bronchoalveolar lavage fluid concentrations of brain-derived neurotrophic factor, suggested to induce nerve remodelling in chronic cough, were also enhanced (day 1: saline, 14.21 pg/ml; bleomycin, 30.09 pg/ml). In summary, our model of bleomycin-induced cough exacerbation may be a valuable tool to investigate cough hypersensitivity and develop antitussive therapies for fibrotic lung diseases. PMID- 26275725 TI - Corrigendum to "Alterations in grooming activity and syntax in heterozygous SERT and BDNF knockout mice: the utility of behavior-recognition tools to characterize mutant mouse phenotypes". PMID- 26275726 TI - The identification of lobeglitazone metabolites in rat liver microsomes and the kinetics of the in vivo formation of the major metabolite M1 in rats. AB - The objective of this study was to elucidate the chemical structure of the metabolites derived from lobeglitazone (LB) during its incubation with rat liver microsomes and to characterize the kinetics of formation of the major metabolite M1 in vivo. Using high performance liquid chromatography coupled with a hybrid quadrupole linear ion trap, the metabolites were derived from LB during its incubation with rat liver microsomes. From various fragmentation patterns obtained from the metabolites, LB was biotransformed into 5 metabolites in the incubation, in which demethylation and hydroxylation appeared to be the principle metabolic pathways in vitro; Amongst the five primary metabolites, M1, a demethylated derivative of LB, appeared to be the major metabolite of LB, based on a comparison on the peak intensities in the ion chromatogram. In a study of the in vivo kinetics of formation of M1 in rats, the rate of formation of M1 from LB was determined to be 0.252 and 0.216mL/min/kg at doses of 0.5mg/kg and 2mg/kg of LB, respectively, suggesting that the kinetics of M1 formation were linear in the dose range tested. Considering the fact that LB is primarily eliminated by hepatic metabolism in rats, the formation of M1 accounts for approximately 7.50 9.76% of the overall elimination of LB in rats. PMID- 26275727 TI - Unraveling the active hypoglycemic agent trigonelline in Balanites aegyptiaca date fruit using metabolite fingerprinting by NMR. AB - Trigonelline (3-carboxy-1-methyl pyridinium) was identified as a relevant bioactivity and taste imparting component in Balanites aegyptiaca fruit, using (1)H NMR of crude extracts without any fractionation or isolation step. The structural integrity of trigonelline was established within the extract matrix via(1)H NMR, (1)H-(1)H COSY, HMQC and HMBC and by comparison with authentic standard. A quantitative (1)H NMR method (qHNMR) was used to determine trigonelline concentrations in the peel and pulp of B. aegyptiaca fruit of 8 and 13mgg(-1), respectively. Trigonelline so far has not been reported from B. aegyptiaca or its genus as it easily escapes LC-MS based detection. Its discovery provides novel insight into the balanite fruits antidiabetic properties as the compound is known for a pronounced hypoglycemic effect. In addition, it is likely to impart the perceptible bitter taste portion to balanites sweet bitter taste. UPLC-MS of the crude extract additionally revealed the fruit flavonoid pattern showing quercetin/isorhamnetin flavonol conjugates in addition to epicatechin, the latter being present at much lower levels. PMID- 26275728 TI - Air pollution in moderately polluted urban areas: How does the definition of "neighborhood" impact exposure assessment? AB - Environmental health studies commonly quantify subjects' pollution exposure in their neighborhood. How this neighborhood is defined can vary, however, leading to different approaches to quantification whose impacts on exposure levels remain unclear. We explore the relationship between neighborhood definition and exposure assessment. NO2, benzene, PM10 and PM2.5 exposure estimates were computed in the vicinity of 10,825 buildings using twelve exposure assessment techniques reflecting different definitions of "neighborhood". At the city scale, its definition does not significantly influence exposure estimates. It does impact levels at the building scale, however: at least a quarter of the buildings' exposure estimates for a 400 m buffer differ from the estimated 50 m buffer value (+/-1.0 MUg/m(3) for NO2, PM10 and PM2.5; and +/-0.05 MUg/m(3) for benzene). This variation is significantly related to the definition of neighborhood. It is vitally important for investigators to understand the impact of chosen assessment techniques on exposure estimates. PMID- 26275729 TI - Body size-dependent toxicokinetics and toxicodynamics could explain intra- and interspecies variability in sensitivity. AB - Ecological risk assessment of chemicals aims at quantifying the likelihood of adverse effects posed to non-target populations and the communities they constitute, often based on lethal concentration estimates for standard test species. There may, however, be intra- and interspecific differences in responses to chemical exposure. Here with the help of a toxicokinetic-toxicodynamic model, we explored whether differential body sizes might explain the observed variability in sensitivity between species and between life-stages of each individual species, for three model organisms, Daphnia magna, Chaoborus crystallinus and Mesocyclops leuckarti. While body size-dependent toxicokinetics could be used to predict intraspecies variation in sensitivity, our results also suggest that changes in both toxicokinetic and toxicodynamic parameters might be needed to describe differential species sensitivity. Accounting for biological traits, like body size, in mechanistic effect models will allow more accurate predictions of chemical effects in size structured populations, ultimately providing mechanistic explanations for species sensitivity distributions. PMID- 26275730 TI - Carcinogenic risk of chromium, copper and arsenic in CCA-treated wood. AB - We showed that 2.1% of 233 pieces of lumber debris after the Great East Japan Earthquake was chromated copper arsenate (CCA)-treated wood. Since hexavalent chromium (Cr), copper (Cu) and pentavalent arsenic (As) in the debris may be diffused in the air via incineration, we exposed human lung normal (BEAS-2B) and carcinoma (A549) cells to Cr, Cu and As at the molar ratio in a representative CCA-treated wood. Co-exposure to 0.10 MUM Cr and 0.06 MUM As, which solely had no effect on colony formation, synergistically promoted colony formation in BEAS-2B cells, but not A549 cells, with activation of the PI3K/AKT pathway. Sole exposure and co-exposure to Cu showed limited effects. Since previous reports showed Cr and As concentrations to which human lungs might be exposed, our results suggest the importance to avoid diffusion of Cr and As in the air via incineration of debris including CCA-treated wood after the disaster. PMID- 26275731 TI - Rare severe mycotic infections in children receiving empirical caspofungin treatment for febrile neutropenia. AB - Empirical antifungal therapy is most often given to patients with leukemia. However breakthrough fungal infections under antifungal therapy are not uncommon. Four children, with hematologic malignant disease developed mycotic breakthrough infections while on empirical caspofungin treatment for a median of 14 (range 11 19) days. Trichosporon asahii was detected in the blood culture of two patients and Geotrichum capitatum in the other two (one patient also had positive cerebrospinal fluid culture). Because the patients' clinical situation worsened, voriconazole was empirically added for two patients three and five days before the agent was detected. The first sterile blood culture was obtained 3-7 days of voriconazole treatment. All patients reached clear cultures but one patient died. One patient with central nervous system infection with G. capitatum had severe neurological sequelae. Very severe fungal infections can occur during empirical caspofungin therapy. Therefore, patients should be followed closely. PMID- 26275732 TI - [Commentary to the letter "Beware of multiplicity problems in clinical trials"]. PMID- 26275733 TI - [Anaesthetic management of excision of a cervical intraspinal tumor with intraoperative neurophysiologic monitoring in a pregnant woman at 29 weeks]. AB - The intraoperative neurophysiological monitoring is a technique used to test and monitor nervous function. This technique has become essential in some neurosurgery interventions, since it avoids neurological injuries during surgery and reduces morbidity. The experience of intraoperative neurophysiological monitoring is limited in some clinical cases due to the low incidence of pregnant women undergoing a surgical procedure. A case is presented of a 29-weeks pregnant woman suffering from a cervical intraspinal tumour with intense pain, which required surgery. The collaboration of a multidisciplinary team composed of anaesthesiologists, neurosurgeons, neurophysiologists and obstetricians, the continuous monitoring of the foetus, the intraoperative neurophysiological monitoring, and maintaining the neurophysiological and utero-placental variables were crucial for the proper development of the surgery. According to our experience and the limited publications in the literature, no damaging effects of this technique were detected at maternal-foetal level. On the contrary, it brings important benefits during the surgery and for the final result. PMID- 26275734 TI - Multimodal treatment of non-small-cell lung cancer. PMID- 26275735 TI - Induction chemoradiation in stage IIIA/N2 non-small-cell lung cancer: a phase 3 randomised trial. AB - BACKGROUND: One of the standard options in the treatment of stage IIIA/N2 non small-cell lung cancer is neoadjuvant chemotherapy and surgery. We did a randomised trial to investigate whether the addition of neoadjuvant radiotherapy improves outcomes. METHODS: We enrolled patients in 23 centres in Switzerland, Germany and Serbia. Eligible patients had pathologically proven, stage IIIA/N2 non-small-cell lung cancer and were randomly assigned to treatment groups in a 1:1 ratio. Those in the chemoradiotherapy group received three cycles of neoadjuvant chemotherapy (100 mg/m(2) cisplatin and 85 mg/m(2) docetaxel) followed by radiotherapy with 44 Gy in 22 fractions over 3 weeks, and those in the control group received neoadjuvant chemotherapy alone. All patients were scheduled to undergo surgery. Randomisation was stratified by centre, mediastinal bulk (less than 5 cm vs 5 cm or more), and weight loss (5% or more vs less than 5% in the previous 6 months). The primary endpoint was event-free survival. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00030771. FINDINGS: From 2001 to 2012, 232 patients were enrolled, of whom 117 were allocated to the chemoradiotherapy group and 115 to the chemotherapy group. Median event-free survival was similar in the two groups at 12.8 months (95% CI 9.7-22.9) in the chemoradiotherapy group and 11.6 months (8.4-15.2) in the chemotherapy group (p=0.67). Median overall survival was 37.1 months (95% CI 22.6-50.0) with radiotherapy, compared with 26.2 months (19.9 52.1) in the control group. Chemotherapy-related toxic effects were reported in most patients, but 91% of patients completed three cycles of chemotherapy. Radiotherapy-induced grade 3 dysphagia was seen in seven (7%) patients. Three patients died in the control group within 30 days after surgery. INTERPRETATION: Radiotherapy did not add any benefit to induction chemotherapy followed by surgery. We suggest that one definitive local treatment modality combined with neoadjuvant chemotherapy is adequate to treat resectable stage IIIA/N2 non-small cell lung cancer. FUNDING: Swiss State Secretariat for Education, Research and Innovation (SERI), Swiss Cancer League, and Sanofi. PMID- 26275736 TI - Hypoglossal nerve palsy following the robotic thyroidectomy for the papillary thyroid carcinoma: A case report. AB - BACKGROUND: Endoscopic surgical techniques with robotic system in the thyroid cancer have been reported to show good results and advantages; however the risk of these techniques has not been fully documented. PRESENTATION OF THE CASE: We experienced an uncommon complicated case of a 20-year-old woman with a papillary thyroid carcinoma. After the robotic thyroidectomy, she complained of the tongue deviation, speech and swallowing difficulties of hypoglossal nerve palsy. DISCUSSION: In this case, a few etiologies could be suggested for the development of hypoglossal nerve palsy. It might be associated with direct stretching or entrapment of hypoglossal nerve during tumor resection; lateral placement of the laryngoscope on the tongue base; the hyperinflation of the laryngeal mask airway; and histological disruption of the intraneural connective tissue and blood circulation. CONCLUSION: Although the robotic surgery is a creative technique and has been known to be safe and effective, the risk of this surgery including traumatic nerve injury should be taken into account before surgery. PMID- 26275737 TI - Occult fracture of the femoral neck associated with extensive osteonecrosis of the femoral head: A case report. AB - INTRODUCTION: Although the subchondral portion of the femoral head is a common site for collapse in osteonecrosis of the femoral head (ONFH), femoral-neck fracture rarely occurs during the course of ONFH. We report a case of occult insufficiency fracture of the femoral neck without conditions predisposing to insufficiency fractures, occurring in association with ONFH. PRESENTATION OF CASE: We report a case of occult fracture of the femoral neck due to extensive ONFH in a 60-year-old man. No abnormal findings suggestive of ONFH were identified on radiographs, and the fracture occurred spontaneously without any trauma or unusual increase in activity. The patient's medical history, age, and good bone quality suggested ONFH as a possible underlying cause. Contrast enhanced magnetic resonance imaging was useful in determining whether the fracture was caused by ONFH or was instead a simple insufficiency fracture caused by steroid use. DISCUSSION: The patient was treated with bipolar hemiarthroplasty, but if we had not suspected ONFH as a predisposing condition, the undisplaced fracture might have been treated by osteosynthesis, and this would have led to nonunion or collapse of the femoral head. To avoid providing improper treatment, clinicians should consider ONFH as a predisposing factor in pathologic fractures of the femoral neck. CONCLUSION: ONFH should be included in the differential diagnosis of insufficiency fracture of the femoral neck. PMID- 26275738 TI - Concomitant endometrial and gallbladder metastasis in advanced multiple metastatic invasive lobular carcinoma of the breast: A rare case report. AB - INTRODUCTION: At time of presentation, fewer than 10% of patients have metastatic breast cancer. The most common sites of metastasis in order of frequency are bone, lung, pleura, soft tissue, and liver. Breast cancer metastasis to the uterus or gallbladder is rare and has infrequently been reported in the English literature. PRESENTATION OF CASE: A 47 year old female with a recent history of thrombocytopenia presented with abnormal vaginal bleeding. Pelvic ultrasound revealed multiple uterine fibroids and endometrial curettings revealed cells consistent with lobular carcinoma of the breast. Breast examination revealed edema and induration of the lower half of the right breast. Biopsy of the right breast revealed invasive lobular carcinoma. Bone marrow aspiration obtained at a previous outpatient visit revealed extensive involvement by metastatic breast carcinoma. Shortly after discharge, the patient presented with acute cholecystitis and underwent cholecystectomy. Microscopic examination of the gallbladder revealed metastatic infiltrating lobular carcinoma. The final diagnosis was invasive lobular carcinoma of the right breast with metastasis to the bone marrow, endometrium, gallbladder, regional lymph nodes, and peritoneum. DISCUSSION: The growth pattern of invasive lobular carcinoma of the breast is unique and poses a challenge in diagnosing the cancer at an early stage. Unlike other types of breast cancer, it tends to metastasize more to the peritoneum, ovary, and gastrointestinal tract. Metastasis to the endometrium or gallbladder is rare. CONCLUSION: Metastatic spread should be considered in the differential diagnosis of patients with invasive lobular breast carcinoma presenting with abnormal vaginal bleeding or acute cholecystitis. PMID- 26275739 TI - Adult Sacrococcygeal Teratoma: The third leg: A rare case report in a 25 year old man. AB - INTRODUCTION: Sacrococcygeal Teratoma (SCT) is a rare benign neoplasm comprised of mixed elements derived from two or more germ cell layers. They are extremely rare in adults. They attract attention because of their gross appearance and bizarre histology. PRESENTATION OF CASE: A 25 year old male presented to Surgical OPD, Government General Hospital, Guntur Medical College, Guntur with a large mass comprising a partially developed 3rd leg and rudimentary external genitalia in the lower back. He complained of cosmetic blemish, difficulty in sitting, sleeping and walking. DISCUSSION: He was diagnosed mature Sacrococcygeal Teratoma Altman Type II based on history, clinical examination, ultrasound, MRI. Histopathology confirmed the diagnosis. He had complete surgical excision with primary wound closure and a good postoperative recovery. A 3-year follow-up using clinical, biochemical and radiological assessment revealed no evidence of recurrence. CONCLUSION: Mature SCT, though very rare in adults, are usually benign. Complete surgical excision remains the mainstay of treatment. PMID- 26275740 TI - Evaluation of hepatic perfusion in the liver graft using fluorescence imaging with indocyanine green. AB - INTRODUCTION: Portal vein thrombosis (PVT) after liver transplantation (LT) is one of serious complications and reportedly ranges from 2% to 13%. PVT impairs the blood perfusion to the grafts and causes the graft dysfunction. PRESENTATION OF CASE: A 60-year-old female underwent living-donor LT with the left liver graft for end-stage liver disease related to chronic hepatitis C. After reperfusion, Indocyanine green (ICG)-fluorescence imaging was performed to confirm the graft perfusion, which pointed out an insufficient perfusion on the surface of segment 4. Following intraoperative ultrasonography revealed thrombus in the portal vein of segment 4, which was successfully removed by heparinized saline flush. DISCUSSION: The most of patients with PVT developed graft failure and resulted in retransplantation. This enhances the importance of the surveillance for PVT in the postoperative period as well as the intraoperative period. However, the modality to identify PVT during surgery is limited mainly to intraoperative ultrasound. ICG-fluorescence imaging can visualize regions with impaired hepatic perfusion due to PVT in real time during LT in addition to visualization of hepatic flows of reconstructed vessels and evaluation of regions with venous occlusion. CONCLUSION: ICG-fluorescence imaging can be simply performed with single ICG injection and is expected to have potential roles to enhance the safety of LT. PMID- 26275741 TI - A Case of Secondary Aortoesophageal Fistula. PMID- 26275742 TI - Acute Urinary Retention Caused by an Ovarian Teratoma-A Unique Pediatric Presentation and Review. AB - BACKGROUND: Acute urinary retention (AUR) is a rare diagnosis both in pediatric and adult female populations, especially when compared to adult males. AUR occurs in women at a rate of 7 in 100,000 per year in a 1:13 female to male ratio. Multiple studies have shown that within the pediatric population AUR is far less common in females and is caused by different pathologies than AUR in adult women. CASE REPORT: We report the case of an 11 year-old prepubescent female who presented to the emergency department with acute urinary retention found to be caused by a mature cystic ovarian teratoma. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Our case is unique in that it describes an ovarian mass leading to AUR which has not previously been described in the pediatric literature. We will review the causes of AUR in the pediatric female population and compare these to the causes of AUR in other populations. PMID- 26275743 TI - A Survey of the First-Hour Basic Care Tasks of Severe Sepsis and Septic Shock in Pediatric Patients and an Evaluation of Medical Simulation on Improving the Compliance of the Tasks. AB - BACKGROUND: Application of the sepsis resuscitation bundle is limited by clinician knowledge, skills, and experience. We used the adjusted first-hour basic care tasks in pediatric patients in three tertiary hospitals in Shanghai, China. OBJECTIVE: The aim of this study is to survey the compliance of the adjusted tasks and to evaluate in situ simulation team training on improving the compliance. METHODS: A prospective observational study was performed with the survey checklists from May 2011 to January 2012 in three pediatric intensive care units. A simulated case scenario was administered to the practitioners in one hospital. RESULTS: Seventy-three patients were enrolled, including 47 patients in one simulation hospital (SH) and 26 patients in two nonsimulation hospitals (NSH). The total compliance of the tasks was 47.9% (35/73). The compliance in the SH was significantly higher compared to that in the NSHs (61.7% [29/47] vs. 23.1% [6/26], p < 0.01). Compared to the SH, the main problems in the NSH were giving intravenous or intraosseous fluid resuscitation in a longer time (35.3 min vs. 19.9 min, p = 0.000), a smaller percentage of measurement of accurate urine output (38.5% vs. 68.1%, p = 0.027), delivering high-flow oxygen (73.1% vs. 93.6%, p = 0.028), and measurement of lactate (69.2% vs. 100%, p = 0.000). CONCLUSIONS: In situ simulation team training is an effective method of teaching the tasks of septic shock care to clinicians and nurses on the front line and of improving the compliance of the tasks. PMID- 26275744 TI - Reciprocal longitudinal associations between substance use and child-to-parent violence in adolescents. AB - Child-to-parent violence (CPV) is a type of violence that has received little attention despite its increasing rates in Western countries. Several models state that substance abuse constitutes a risk factor for aggressive behavior and that relationships among these variables can be reciprocal. In this study, the temporal relationships among substance use and physical and psychological CPV were examined. A sample of 981 adolescents (mean age = 15.22 years, SD = 1.2 years) completed measures of substance use and CPV at three time points (T1, T2, and T3) spaced 6 months apart. The results indicated that T1 levels of substance use predicted an increase in psychological CPV at T2 and that T2 levels of substance use predicted an increase in physical CPV at T3. Additionally, several mediational mechanisms emerged between substance use at T1 and CPV at T3. Neither physical nor psychological CPV predicted an increase in substance use at any time. Multiple comparisons indicated that the predictive association between substance use and physical aggression against parents was significant only in boys. These findings suggest that preventive programs for CPV should include specific components for reducing substance use. PMID- 26275745 TI - A systematic review of the association between family meals and adolescent risk outcomes. AB - OBJECTIVE: To conduct a systematic review of the literature examining the relationship between family meals and adolescent health risk outcomes. METHODS: We performed a systematic search of original empirical studies published between January 1990 and September 2013. Based on data from selected studies, we conducted logistic regression models to examine the correlates of reporting a protective association between frequent family meals and adolescent outcomes. RESULTS: Of the 254 analyses from 26 selected studies, most reported a significant association between family meals and the adolescent risk outcome-of interest. However, model analyses which controlled for family connectedness variables, or used advanced empirical methods to account for family-level confounders, were less likely than unadjusted models to report significant relationships. CONCLUSIONS: The type of analysis conducted was significantly associated with the likelihood of finding a protective relationship between family meals and the adolescent outcome-of-interest, yet very few studies are using such methods in the literature. PMID- 26275746 TI - Health complaints among adolescents: Associations with more screen-based behaviours and less physical activity. AB - In this study, we investigated the relationship between screen-based behaviours, physical activity, and health complaints (headaches, feeling low, irritability, and nervousness). Screen-based behaviour included TV viewing, computer use, and time spent playing video games. Data were collected from 4462 Portuguese adolescents (2394 girls) aged 11-16 years. Girls who reported engaging in more screen-based behaviour (hours/day) also reported having more headaches, feeling lower, being more irritable, and feeling more nervous. Boys who reported more screen time were more irritable. Physical activity (times/week) was negatively associated with reports of feeling nervous among girls, and with headaches, feeling low, irritability, and feeling nervous among boys. Considering that time spent using the computer is related with more health complaints, and physical activity was related with fewer health complaints among boys, it is important to develop strategies to reduce adolescents' computer screen time, and to promote physical activity. PMID- 26275747 TI - Parental and emerging adult psychopathology: Moderated mediation by gender and affect toward parents. AB - Current research indicates that children tend to view parents with psychopathology more negatively and children who hold negative perceptions of parents are at a greater risk for psychopathology. Yet, less research examines how parental psychopathology influences offspring psychopathology through affect toward parents. The current study tested a model that examined the associations among parental psychopathology, positive affect toward parents, and emerging adult psychopathology. Associations were expected to be partly indirect via positive affect toward parents and emerging adult gender was expected to moderate these associations. Results indicated gender-moderated mediation with significant effects found for males but not females. Results from the current study emphasize the importance of examining affect toward parents as a risk factor for emerging adult psychopathology. Additionally, results of the current study demonstrate the importance of examining the role of emerging adult gender as a potential moderator in these relationships. PMID- 26275748 TI - Loss of Siah2 does not impact angiogenic potential of murine endothelial cells. AB - Angiogenesis is triggered in response to hypoxia under many circumstances, from healthy cells and tissues during embryogenesis to pathological conditions like the formation of new blood vessels to supply tumours and promote invasive cancer. Siah2 has been shown to regulate the hypoxia pathway upstream of hypoxia-induced transcription factor subunit Hif-1alpha, and therefore may play an important role in angiogenesis in response to hypoxic stress in endothelial cells. This study aims to investigate the basic function of Siah2 in endothelial cells under hypoxia and to test the ability of Siah2 deficient cells to mount an angiogenic response when deprived of oxygen. We and others have previously shown that Siah2 is crucial for mediating the hypoxic response in many different cell types studied. In this study however, we describe that Siah2(-/-) endothelial cells have an intact hypoxic signalling pathway, including Hif-1alpha stabilisation and gene expression, the first report of a tissue or cell lineage in which the loss of Siah2 does not seem to impact hypoxic response signalling. In mice, the infiltration of Siah2(-/-) endothelial cells into a Matrigel plug containing a VEGF-A attractant was similar compared with wildtype endothelial cells. Ex vivo however, there was a reduced capacity of Siah2(-/-) aorta to form tubes or new vessels. Thus, we conclude that Siah2 is not essential for the hypoxic response of endothelial cells. PMID- 26275750 TI - Countries must prepare for more frequent food shortages, says task force. PMID- 26275749 TI - Identification of novel isoprene synthases through genome mining and expression in Escherichia coli. AB - Isoprene is a naturally produced hydrocarbon emitted into the atmosphere by green plants. It is also a constituent of synthetic rubber and a potential biofuel. Microbial production of isoprene can become a sustainable alternative to the prevailing chemical production of isoprene from petroleum. In this work, sequence homology searches were conducted to find novel isoprene synthases. Candidate sequences were functionally expressed in Escherichia coli and the desired enzymes were identified based on an isoprene production assay. The activity of three enzymes was shown for the first time: expression of the candidate genes from Ipomoea batatas, Mangifera indica, and Elaeocarpus photiniifolius resulted in isoprene formation. The Ipomoea batatas isoprene synthase produced the highest amounts of isoprene in all experiments, exceeding the isoprene levels obtained by the previously known Populus alba and Pueraria montana isoprene synthases that were studied in parallel as controls. PMID- 26275751 TI - Clinical Utility of Measuring Epicardial Adipose Tissue Thickness with Echocardiography Using a High-Frequency Linear Probe in Patients with Coronary Artery Disease. AB - BACKGROUND: The relationship between epicardial adipose tissue (EAT) and coronary artery disease (CAD) has recently attracted a great deal of attention in the medical community. The objective of this study was to determine whether measuring EAT thickness in the anterior interventricular groove (AIG) using echocardiography is feasible and whether this index can be a marker of CAD. METHODS: A total of 311 patients (mean age, 67 +/- 11 years; 208 men) who underwent coronary angiography between December 2011 and December 2013 were prospectively enrolled. EAT-AIG thickness and EAT thickness on the free wall of the right ventricle (RV) were measured in systole using a high-frequency linear probe. Seventy-one patients who underwent multidetector-row computed tomography were enrolled to validate the method for measuring EAT thickness using echocardiography. Subjects were divided into two groups, those with and without significant coronary stenosis, on the basis of findings on coronary angiography (>= 75% luminal narrowing). RESULTS: EAT-AIG thickness measured using echocardiography was validated by computed tomography. EAT-AIG thickness was strongly correlated with EAT volume (r = 0.714, P < .001). The CAD group had thicker EAT-AIG than the non-CAD group (8.3 +/- 3.0 vs 6.3 +/- 2.5 mm, P < .001). EAT-RV thickness was greater in the CAD group than in the non-CAD group (5.0 +/- 2.1 vs 4.4 +/- 2.3 mm, P = .009) as well. The area under the curve on receiver operating characteristic curve analysis of EAT-AIG thickness for predicting CAD was 0.704, which was higher than the EAT-RV thickness. CONCLUSIONS: Measuring EAT thickness using echocardiography with a high-frequency linear probe was validated with computed tomography. EAT-AIG was thicker in the CAD group than in the non CAD group, as was EAT-RV thickness. This noninvasive index may have potential as a diagnostic marker for predicting coronary atherosclerosis. PMID- 26275753 TI - Food web of the intertidal rocky shore of the west Portuguese coast - Determined by stable isotope analysis. AB - The characterization of food web structure, energy pathways and trophic linkages is essential for the understanding of ecosystem functioning. Isotopic analysis was performed on food web components of the rocky intertidal ecosystem in four sites along the Portuguese west coast. The aim was to 1) determine the general food web structure, 2) estimate the trophic level of the dominant organisms and 3) track the incorporation of organic carbon of different origins in the diet of the top consumers. In this food web, fish are top consumers, followed by shrimp. Anemones and gastropods are intermediate consumers, while bivalves and zooplankton are primary consumers. Macroalgae Bifurcaria bifurcata, Ulva lactuca, Fucus vesiculosus, Codium sp. and phytoplankton are the dominant producers. Two energy pathways were identified, pelagic and benthic. Reliance on the benthic energy pathway was high for many of the consumers but not as high as previously observed in subtidal coastal food webs. The maximum TL was 3.3, which is indicative of a relatively short food web. It is argued that the diet of top consumers relies directly on low levels of the food web to a considerable extent, instead of on intermediate levels, which shortens the trophic length of the food web. PMID- 26275752 TI - Early Bioprosthetic Valve Failure: Mechanistic Insights via Correlation between Echocardiographic and Operative Findings. AB - Bioprosthetic valves are increasingly implanted, with generally consistent and durable results. Early bioprosthetic valve failure is uncommon, and most clinicians are unfamiliar with the spectrum of early structural complications involving bioprostheses. In this review, the authors organize causes of early bioprosthetic valve failure according to possible pathogenesis, demonstrate the correlation between echocardiographic and anatomic findings, and discuss potential treatments. First, they address early bioprosthetic valve stenosis secondary to thrombosis. Next, they discuss excessive pannus formation, a hitherto rarely described cause of early bioprosthetic valve failure. Finally, the authors address early structural valve deterioration mediated by calcification or primary tears. Illustrative examples with relevant echocardiographic and operative findings are provided. PMID- 26275754 TI - Ocean warming ameliorates the negative effects of ocean acidification on Paracentrotus lividus larval development and settlement. AB - Ocean warming and acidification both impact marine ecosystems. All organisms have a limited body temperature range, outside of which they become functionally constrained. Beyond the absolute extremes of this range, they cannot survive. It is hypothesized that some stressors can present effects that interact with other environmental variables, such as ocean acidification (OA) that have the potential to narrow the thermal range where marine species are functional. An organism's response to ocean acidification can therefore be highly dependent on thermal conditions. This study evaluated the combined effects of predicted ocean warming conditions and acidification, on survival, development, and settlement, of the sea urchin Paracentrotus lividus. Nine combined treatments of temperature (19.0, 20.5 and 22.5 degrees C) and pH (8.1, 7.7 and 7.4 units) were carried out. All of the conditions tested were either within the current natural ranges of seawater pH and temperature or are within the ranges that have been predicted for the end of the century, in the sampling region (Canary Islands). Our results indicated that the negative effects of low pH on P. lividus larval development and settlement will be mitigated by a rise in seawater temperature, up to a thermotolerance threshold. Larval development and settlement performance of the sea urchin P. lividus was enhanced by a slight increase in temperature, even under lowered pH conditions. However, the species did show negative responses to the levels of ocean warming and acidification that have been predicted for the turn of the century. PMID- 26275755 TI - Investigation on the proteome response of transplanted blue mussel (Mytilus sp.) during a long term exposure experiment at differently impacted field stations in the German Bight (North Sea). AB - In a pilot field study the proteome response of Mytilus sp. was analyzed in relation to the concentration of different trace metal contaminants. Over a period of eight month test organisms have been exposed at a near-shore station in the anthropogenic impacted estuary of the river Elbe and at an off-shore station in the vicinity of the Island of Helgoland in the German Bight (North Sea). The stations differ in their hydrological as well as chemical characteristics. The physiological biomarkers, such as condition index which have been continuously monitored during the experiment clearly indicate the effects of the different environmental conditions. Multiple protein abundance changes were detected utilizing the techniques of two dimensional gel electrophoresis (2dGE) and consequently proteins arising as potential candidates for ecotoxicological monitoring have been identified by MALDI-ToF and ToF/ToF mass spectrometry. Different cytoskeletal proteins, enzymes of energy metabolism, stress proteins and one protein relevant for metal detoxification have been pointed out. PMID- 26275756 TI - Clinical audit: why, where and how? PMID- 26275757 TI - Malignant melanoma metastasis in the form of non-solid nodules: Diagnosis by percutaneous lung biopsy. PMID- 26275758 TI - An Exploratory Investigation of Communication Technologies to Alleviate Communicative Difficulties and Depression in Older Adults. AB - OBJECTIVE: To explore associations between older adults' communicative difficulties, depressive symptoms, and e-mail and telephone use with adult children. METHOD: We examined these associations using data from 1,634 participants (age M = 71.16, SD = 0.89; 54% female) in the 2011 wave of the Wisconsin Longitudinal Study. RESULTS: Better vision and worse speech were associated with more frequent e-mail contact with the selected child. Worse hearing was associated with more depressive symptoms for participants with low e mail use but not for those with average or high e-mail use. Telephone use was not associated with communicative difficulties or depressive symptoms. DISCUSSION: This study provides preliminary evidence that older adults might use communication technologies such as e-mail in their close relationships to compensate for communicative difficulties. The text-based format of e-mail might also help older adults mitigate hearing impairments and associated depressive symptoms. PMID- 26275759 TI - Fatal cardiac small-vessel involvement in ANCA-associated vasculitis: an autopsy case report. AB - An 80-year-old Japanese man, who had fever and generalized fatigue not improved by antibiotics, was admitted to our hospital. Laboratory data indicative of renal dysfunction and antineutrophil cytoplasmic antibody (ANCA) in the serum led to the consideration of ANCA-associated vasculitis as a differential diagnosis. However, before the diagnostic confirmation, he was found dead on the bed. Autopsy revealed necrotizing crescentic glomerulonephritis in the kidneys. In addition, necrotizing granulomatous vasculitis with infiltration of multinucleated giant cells and neutrophils but not eosinophils was present in multiple organs. The direct cause of death was presumed as cardiac arrest by lethal arrhythmia because vasculitic lesions were distributed widely in the cardiac walls, acute congestion was observed in the systemic organs, and other causes of death were ruled out. This report presents the unusual manifestation of cardiac small-vessel involvement in ANCA-associated vasculitis related to sudden death. PMID- 26275760 TI - Transdiagnostic cognitive behaviour therapy for adolescents with an eating disorder who are not underweight. AB - Little is known about the treatment of adolescents with an eating disorder who are not underweight. Enhanced cognitive behaviour therapy (CBT-E) is a potential option as it is a treatment for adult patients with eating disorders of this type and it has been shown to be effective with adolescent patients who are underweight. The aim of the present cohort study was to evaluate the effects of CBT-E on non-underweight adolescents with an eating disorder. Sixty-eight adolescent patients with an eating disorder and a body mass index (BMI) centile corresponding to an adult BMI >= 18.5 were recruited from consecutive referrals to a community-based eating disorder clinic. Each was offered 20 sessions of CBT E over 20 weeks. Three-quarters completed the full 20 sessions. There was a marked treatment response with two-thirds (67.6%, intent-to-treat) having minimal residual eating disorder psychopathology by the end of treatment. CBT-E therefore appears to be a promising treatment for those adolescents with an eating disorder who are not underweight. PMID- 26275761 TI - The feasibility of improving CBT for childhood anxiety disorders through a dismantling study. AB - This preliminary randomized controlled trial (RCT) examines the feasibility of dismantling cognitive behavioral therapy (CBT) for childhood anxiety disorders. Fourteen children (10 girls) ages 7 to 14 (m = 10.2) with social phobia, generalized anxiety disorder, separation anxiety disorder, or panic disorder were randomized to receive 6 sessions of either a) the pre-exposure anxiety management strategies presented in traditional CBT, or b) parent-coached exposure therapy. The sample was selected from a treatment seeking population and is representative of children in clinical settings. Examination of fidelity ratings, dropouts, and satisfaction ratings indicated that the interventions were distinguishable, safe, and tolerable. The overall sample improved significantly with pre-post effect sizes generally in the large range for both conditions. Between-group effect sizes indicating greater improvement with parent-coached exposure therapy were moderate or large for ten of 12 variables (i.e., 0.53 to 1.52). Re-evaluation after three months of open treatment suggested that the intervention emphasizing exposure early maintained its superiority while requiring fewer appointments. PMID- 26275762 TI - Assessment the performance of classification methods in water quality studies, A case study in Karaj River. AB - To show the performance of classification methods in water quality studies, linear discriminant, and Naive Bayesian classification methods were applied at nine sampling stations with respect to four parameters including COD, nitrite, nitrate, and total coliforms (selected from ten water quality variables) in Karaj River, Iran. To fulfill the goals of this study, the sampling stations were first separated into two groups using cluster analysis. Rural wastewater was the main source of pollution in the first group, whereas the quality of water in the second group has been degraded mainly by organic and agricultural pollution. In order to have an independent group against which the performance of other classification methods is considered, three cross-validation methods including twofold, leave-one-out, and holdout methods were utilized to retain an independent test set. The results of cross-validation for the linear discriminant analysis show that, except for the leave-one-out method with 11.1 % misclassification error, the overall performance has been the same as that of the training data set. Therefore, it has outperformed compared with that of Naive Bayesian classification method. However, even though in situations where the correlation coefficient among the parameters is low, the latest method can offer the same performance as that of linear discriminant analysis as well. A sensitivity analysis was implemented using ten water quality variables (pH, COD, EC, TDA, turbidity, nitrate, nitrite, sulfate, TC, and FC) to find the most important variables in the classification of Karaj River showing that turbidity, next to COD, pH, nitrate, and sulfate, have had the most contribution in this field. PMID- 26275763 TI - A WebGIS platform to monitor environmental conditions in ports and their surroundings in South Eastern Europe. AB - The scope of this work is to describe the design and development of a web-based Geographic Information System (GIS) application and highlight its usefulness regarding monitoring and evaluating environmental conditions in several ports and their surroundings in the greater South East Europe (SEE). The system receives inputs and handles two kinds of data that are processed and illustrated through maps and graphs at various temporal and spatial scales in this informational platform. The aforementioned data consists of point measurements from stations operating in the area of SEE ports as well as satellite date sets derived monthly for a period of 10 to 12 years, in terms of sea surface temperature, chlorophyll a, and colored dissolved organic matter (CDOM). The WebGIS platform is based on the client-server model and uses Google Maps API services for data plotting. Advanced designing and development tools and methodologies are used. The available valuable data render the application into a trustful and accurate provider of visual environmental interest information regarding the main ports of southeastern Europe and their surroundings that would operate as a guide for an environmentally sustainable future of ports and sea corridors in SEE. PMID- 26275764 TI - Photosynthetic use of inorganic carbon in deep-water kelps from the Strait of Gibraltar. AB - Mechanisms of inorganic carbon assimilation were investigated in the four deep water kelps inhabiting sea bottoms at the Strait of Gibraltar; these species are distributed at different depths (Saccorhiza polysiches at shallower waters, followed by Laminaria ochroleuca, then Phyllariopsis brevipes and, at the deepest bottoms, Phyllariopsis purpurascens). To elucidate the capacity to use HCO3(-) as a source of inorganic carbon for photosynthesis in the kelps, different experimental approaches were used. Specifically, we measured the irradiance saturated gross photosynthetic rate versus pH at a constant dissolved inorganic carbon (DIC) concentration of 2 mM, the irradiance-saturated apparent photosynthesis (APS) rate versus DIC, the total and the extracellular carbonic anhydrase (CAext), the observed and the theoretical photosynthetic rates supported by the spontaneous dehydration of HCO3(-) to CO2, and the delta(13)C signature in tissues of the algae. While S. polyschides and L. ochroleuca showed photosynthetic activity at pH 9.5 (around 1.0 umol O2 m(-2) s(-1)), the activity was close to zero in both species of Phyllariopsis. The APS versus DIC was almost saturated for the DIC values of natural seawater (2 mM) in S. polyschides and L. ochroleuca, but the relationship was linear in P. brevipes and P. purpurascens. The four species showed total and CAext activities but the inhibition of the CAext originated the observed photosynthetic rates at pH 8.0 to be similar to the theoretical rates that could be supported by the spontaneous dehydration of HCO3( ). The isotopic (13)C signatures ranged from -17.40 +/- 1.81 to -21.11 +/- 1.73 0/00 in the four species. Additionally, the delta(13)C signature was also measured in the deep-water Laminaria rodriguezii growing at 60-80 m, showing even a more negative value of -26.49 +/- 1.25 0/00. All these results suggest that the four kelps can use HCO3(-) as external carbon source for photosynthesis mainly by the action of external CAext, but they also suggest that the species inhabiting shallower waters show a higher capacity than the smaller kelps living in deeper waters. In fact, the photosynthesis in the two Phyllariopsis species could be accomplished by the spontaneous dehydration of HCO3(-) to CO2. These differences in the capacity to use HCO3(-) in photosynthesis among species could be important considering the increasing levels of atmospheric CO2 predicted for the near future. PMID- 26275765 TI - Ubiquitous Structural Signaling in Bacterial Phytochromes. AB - The phytochrome family of light-switchable proteins has long been studied by biochemical, spectroscopic and crystallographic means, while a direct probe for global conformational signal propagation has been lacking. Using solution X-ray scattering, we find that the photosensory cores of several bacterial phytochromes undergo similar large-scale structural changes upon red-light excitation. The data establish that phytochromes with ordinary and inverted photocycles share a structural signaling mechanism and that a particular conserved histidine, previously proposed to be involved in signal propagation, in fact tunes photoresponse. PMID- 26275766 TI - Patient and family experiences with accessing telephone cancer treatment symptom support: a descriptive study. AB - PURPOSE: Assess patient and family member experiences with telephone cancer treatment symptom support. METHODS: Descriptive study guided by the Knowledge-to Action Framework. Patients and family members who received telephone support for a cancer treatment symptom within the last month at one of three ambulatory cancer programs (Nova Scotia, Ontario, Quebec) were eligible. An adapted Short Questionnaire for Out-of-hours Care instrument was analyzed with univariate statistics. RESULTS: Of 105 participants, 83 % telephoned about themselves and 17 % for a family member. Participants received advice over the telephone (90 %) and were advised to go to emergency (13 %) and/or the clinic (9 %). Two left a message and were not called back. Participants were "very satisfied" with the manner of nurse or doctor (58 %), explanation about problem (56 %), treatment/advice given (54 %), way call was handled (48 %), getting through (40 %), and wait time to speak to a nurse or doctor (38 %). The proportion "dissatisfied" or "very dissatisfied" for the above items was 4, 5, 9, 11, 10, and 14 %, respectively. Suggestions were shorter call back time, weekend access to telephone support, more knowledgeable advice on self-care strategies, more education at discharge, and shared documentation on calls to avoid repetition and improve continuity. CONCLUSIONS: Most patients and family members who responded to the survey were satisfied with telephone-based cancer treatment symptom support. Programs could improve telephone support services by providing an estimated time for callback, ensuring that nurses have access to and use previous call documentation, and enhancing patient education on self-care strategies for managing and triaging treatment-related symptoms. PMID- 26275767 TI - Patient housing barriers to hematopoietic cell transplantation: results from a mixed-methods study of transplant center social workers. AB - PURPOSE: Hematopoietic cell transplantation (HCT) is performed in select centers in the United States (U.S.), and patients are often required to temporarily relocate to receive care. The purpose of this study was to identify housing barriers impacting access to HCT and potential solutions. METHODS: A mixed methods primary study of HCT social workers was conducted to learn about patient housing challenges and solutions in place that help address those barriers. Three telephone focus groups were conducted with adult and pediatric transplant social workers (n = 15). Focus group results informed the design of a national survey. The online survey was e-mailed to a primary social worker contact at 133 adult and pediatric transplant centers in the U.S. Transplant centers were classified based on the patient population cared for by the social worker. RESULTS: The survey response rate was 49%. Among adult programs (n = 45), 93% of centers had patients that had to relocate closer to the transplant center to proceed with HCT. The most common type of housing option offered was discounted hotel rates. Among pediatric programs (n = 20), 90% of centers had patients that had to relocate closer to the transplant center to proceed with HCT. Ronald McDonald House was the most common option available. CONCLUSIONS: This study is the first to explore housing challenges faced by patients undergoing HCT in the U.S. from the perspective of social workers and to highlight solutions that centers use. Transplant centers will benefit from this knowledge by learning about options for addressing housing barriers for their patients. PMID- 26275768 TI - Effects of a self-managed home-based walking intervention on psychosocial health outcomes for breast cancer patients receiving chemotherapy: a randomised controlled trial. AB - PURPOSE: This study evaluated the effectiveness of a self-managed home-based moderate intensity walking intervention on psychosocial health outcomes among breast cancer patients undergoing chemotherapy. METHODS: The randomised controlled trial compared a self-managed, home-based walking intervention to usual care alone among breast cancer patients receiving chemotherapy. Outcome measures included changes in self-report measures of anxiety, depression, fatigue, self-esteem, mood and physical activity. Fifty participants were randomised to either the intervention group (n = 25), who received 12 weeks of moderate intensity walking, or the control group (n = 25) mid-way through chemotherapy. Participants in the intervention group were provided with a pedometer and were asked to set goals and keep weekly diaries outlining the duration, intensity and exertion of their walking. Levels of psychosocial functioning and physical activity were assessed pre- and post-intervention in both groups. RESULTS: The intervention had positive effects on fatigue (F = 5.77, p = 0.02), self-esteem (F = 8.93, p <= 0.001), mood (F = 4.73, p = 0.03) and levels of physical activity (x (2) = 17.15, p = 0.0011) but not anxiety (F = 0.90, p = 0.35) and depression (F = 0.26, p = 0.60) as assessed using the HADS. We found an 80% adherence rate to completing the 12-week intervention and recording weekly logs. CONCLUSION: This self-managed, home-based intervention was beneficial for improving psychosocial well-being and levels of physical activity among breast cancer patients treated with chemotherapy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN50709297. PMID- 26275769 TI - Feasibility of Cognitively-Based Compassion Training (CBCT) for breast cancer survivors: a randomized, wait list controlled pilot study. AB - PURPOSE: This study assessed the feasibility of a meditation-based program called Cognitively-Based Compassion Training (CBCT) with breast cancer survivors. Enrollment and participant satisfaction with a novel intervention, adherence to program requirements, and differences between the intervention group and wait list controls on self-report measures were also assessed. Additionally, cortisol, a stress-related endocrine biomarker, was assessed. METHODS: Participants (n = 33) were randomly assigned to CBCT or the wait list. CBCT provided eight weekly, 2-h classes and a "booster" CBCT session 4 weeks later. CBCT participants were expected to attend classes and meditate between classes at least three times per week. Pre-/post-intervention and follow-up questionnaires measured symptom change (depression, intrusive thoughts, perceived stress, fear of cancer recurrence, fatigue/vitality, loneliness, and quality of life). Saliva samples were collected at the same periods to assess the slope of diurnal cortisol activity. RESULTS: Enrollment, class attendance, home practice time, and patient satisfaction exceeded expectations. Compared to controls, post-intervention, the CBCT group showed suggestions of significant improvements in depression, avoidance of intrusive thoughts, functional impairment associated with fear of recurrence, mindfulness, and vitality/fatigue. At follow-up, less perceived stress and higher mindfulness were also significant in the CBCT group. No significant changes were observed on any other measure including diurnal cortisol activity. CONCLUSIONS: Within the limits of a pilot feasibility study, results suggest that CBCT is a feasible and highly satisfactory intervention potentially beneficial for the psychological well-being of breast cancer survivors. However, more comprehensive trials are needed to provide systematic evidence. RELEVANCE: CBCT may be very beneficial for improving depression and enhancing well-being during breast cancer survivorship. PMID- 26275770 TI - ACE2 and vasoactive peptides: novel players in cardiovascular/renal remodeling and hypertension. AB - The renin-angiotensin system (RAS) is a key component of cardiovascular physiology and homeostasis due to its influence on the regulation of electrolyte balance, blood pressure, vascular tone and cardiovascular remodeling. Deregulation of this system contributes significantly to the pathophysiology of cardiovascular and renal diseases. Numerous studies have generated new perspectives about a noncanonical and protective RAS pathway that counteracts the proliferative and hypertensive effects of the classical angiotensin-converting enzyme (ACE)/angiotensin (Ang) II/angiotensin type 1 receptor (AT1R) axis. The key components of this pathway are ACE2 and its products, Ang-(1-7) and Ang-(1 9). These two vasoactive peptides act through the Mas receptor (MasR) and AT2R, respectively. The ACE2/Ang-(1-7)/MasR and ACE2/Ang-(1-9)/AT2R axes have opposite effects to those of the ACE/Ang II/AT1R axis, such as decreased proliferation and cardiovascular remodeling, increased production of nitric oxide and vasodilation. A novel peptide from the noncanonical pathway, alamandine, was recently identified in rats, mice and humans. This heptapeptide is generated by catalytic action of ACE2 on Ang A or through a decarboxylation reaction on Ang-(1-7). Alamandine produces the same effects as Ang-(1-7), such as vasodilation and prevention of fibrosis, by interacting with Mas-related GPCR, member D (MrgD). In this article, we review the key roles of ACE2 and the vasoactive peptides Ang-(1 7), Ang-(1-9) and alamandine as counter-regulators of the ACE-Ang II axis as well as the biological properties that allow them to regulate blood pressure and cardiovascular and renal remodeling. PMID- 26275771 TI - The relationship between craniofacial development and hypodontia in patients with Down syndrome. AB - BACKGROUND/OBJECTIVE: Hypodontia is often seen in people with Down syndrome (DS). In the normal population, persons with hypodontia have a shorter cranial base and a hypoplastic maxilla, leading to a skeletal Class III tendency and a reduced face height. The purpose of this study was to examine craniofacial morphology in patients with DS at different ages and the influence of hypodontia on their craniofacial morphology. MATERIALS AND METHODS: A comparative cross-sectional study was conducted in 63 children with DS (6-19 years old; 28 males and 35 females) at a Centre for Special Care Dentistry in Rotterdam, the Netherlands (CBT Rijnmond). Digital lateral cephalograms were obtained from all subjects and a cephalometric analysis was performed. The subjects were divided into a group with hypodontia (13 males and 25 females) and a group without hypodontia (15 males and 10 females). RESULTS: Significant results included a decrease in antero posterior relationship of upper and lower jaw (ANB angle -0.331 degrees per year, P = 0.044) and a decrease in vertical dimension (S-N_Go-Gn angle -0.72 degrees per year, P = 0.039) over the years in subjects with hypodontia compared to subjects without hypodontia. CONCLUSION: The process of growth in DS patients is towards a reversed overjet. Hypodontia seems to have an additional effect on this development. The management of hypodontia as part of the complete treatment of dental development in DS children is important because it strongly influences the jaw relationship. PMID- 26275772 TI - Mental health care use in adolescents with and without mental disorders. AB - The aim of the study was to estimate the proportion of adolescents with and without a psychiatric diagnosis receiving specialist mental health care and investigate their problem levels as well as utilization of other types of mental health care to detect possible over- and undertreatment. Care utilization data were linked to psychiatric diagnostic data of 2230 adolescents participating in the TRAILS cohort study, who were assessed biannually starting at age 11. Psychiatric diagnoses were established at the fourth wave by the Composite International Diagnostic Interview. Self-, parent- and teacher-reported emotional and behavioral problems and self-reported mental health care use were assessed at all four waves. Of all diagnosed adolescents, 35.3 % received specialist mental health care. This rate increased to 54.5 % when three or more disorders were diagnosed. Almost a third (28.5 %) of specialist care users had no psychiatric diagnosis; teachers gave them relatively high ratings on attention and impulsivity subscales. Diagnosed adolescents without specialist mental health care also reported low rates of other care use. We found no indication of overtreatment. Half of the adolescents with three or more disorders do not receive specialist mental health care nor any other type of care, which might indicate unmet needs. PMID- 26275773 TI - Noncanoncial signal recognition particle RNAs in a major eukaryotic phylum revealed by purification of SRP from the human pathogen Cryptococcus neoformans. AB - Despite conservation of the signal recognition particle (SRP) from bacteria to man, computational approaches have failed to identify SRP components from genomes of many lower eukaryotes, raising the possibility that they have been lost or altered in those lineages. We report purification and analysis of SRP in the human pathogen Cryptococcus neoformans, providing the first description of SRP in basidiomycetous yeast. The C. neoformans SRP RNA displays a predicted structure in which the universally conserved helix 8 contains an unprecedented stem-loop insertion. Guided by this sequence, we computationally identified 152 SRP RNAs throughout the phylum Basidiomycota. This analysis revealed additional helix 8 alterations including single and double stem-loop insertions as well as loop diminutions affecting RNA structural elements that are otherwise conserved from bacteria to man. Strikingly, these SRP RNA features in Basidiomycota are accompanied by phylum-specific alterations in the RNA-binding domain of Srp54, the SRP protein subunit that directly interacts with helix 8. Our findings reveal unexpected fungal SRP diversity and suggest coevolution of the two most conserved SRP features-SRP RNA helix 8 and Srp54-in basidiomycetes. Because members of this phylum include important human and plant pathogens, these noncanonical features provide new targets for antifungal compound development. PMID- 26275774 TI - Mapping the interactions of the single-stranded DNA binding protein of bacteriophage T4 (gp32) with DNA lattices at single nucleotide resolution: polynucleotide binding and cooperativity. AB - We here use our site-specific base analog mapping approach to study the interactions and binding equilibria of cooperatively-bound clusters of the single stranded DNA binding protein (gp32) of the T4 DNA replication complex with longer ssDNA (and dsDNA) lattices. We show that in cooperatively bound clusters the binding free energy appears to be equi-partitioned between the gp32 monomers of the cluster, so that all bind to the ssDNA lattice with comparable affinity, but also that the outer domains of the gp32 monomers at the ends of the cluster can fluctuate on and off the lattice and that the clusters of gp32 monomers can slide along the ssDNA. We also show that at very low binding densities gp32 monomers bind to the ssDNA lattice at random, but that cooperatively bound gp32 clusters bind preferentially at the 5'-end of the ssDNA lattice. We use these results and the gp32 monomer-binding results of the companion paper to propose a detailed model for how gp32 might bind to and interact with ssDNA lattices in its various binding modes, and also consider how these clusters might interact with other components of the T4 DNA replication complex. PMID- 26275775 TI - Mapping the interactions of the single-stranded DNA binding protein of bacteriophage T4 (gp32) with DNA lattices at single nucleotide resolution: gp32 monomer binding. AB - Combining biophysical measurements on T4 bacteriophage replication complexes with detailed structural information can illuminate the molecular mechanisms of these 'macromolecular machines'. Here we use the low energy circular dichroism (CD) and fluorescent properties of site-specifically introduced base analogues to map and quantify the equilibrium binding interactions of short (8 nts) ssDNA oligomers with gp32 monomers at single nucleotide resolution. We show that single gp32 molecules interact most directly and specifically near the 3'-end of these ssDNA oligomers, thus defining the polarity of gp32 binding with respect to the ssDNA lattice, and that only 2-3 nts are directly involved in this tight binding interaction. The loss of exciton coupling in the CD spectra of dimer 2-AP (2 aminopurine) probes at various positions in the ssDNA constructs, together with increases in fluorescence intensity, suggest that gp32 binding directly extends the sugar-phosphate backbone of this ssDNA oligomer, particularly at the 3'-end and facilitates base unstacking along the entire 8-mer lattice. These results provide a model (and 'DNA map') for the isolated gp32 binding to ssDNA targets, which serves as the nucleation step for the cooperative binding that occurs at transiently exposed ssDNA sequences within the functioning T4 DNA replication complex. PMID- 26275776 TI - The WRN exonuclease domain protects nascent strands from pathological MRE11/EXO1 dependent degradation. AB - The WRN helicase/exonuclease protein is required for proper replication fork recovery and maintenance of genome stability. However, whether the different catalytic activities of WRN cooperate to recover replication forks in vivo is unknown. Here, we show that, in response to replication perturbation induced by low doses of the TOP1 inhibitor camptothecin, loss of the WRN exonuclease resulted in enhanced degradation and ssDNA formation at nascent strands by the combined action of MRE11 and EXO1, as opposed to the limited processing of nascent strands performed by DNA2 in wild-type cells. Nascent strand degradation by MRE11/EXO1 took place downstream of RAD51 and affected the ability to resume replication, which correlated with slow replication rates in WRN exonuclease deficient cells. In contrast, loss of the WRN helicase reduced exonucleolytic processing at nascent strands and led to severe genome instability. Our findings identify a novel role of the WRN exonuclease at perturbed forks, thus providing the first in vivo evidence for a distinct action of the two WRN enzymatic activities upon fork stalling and providing insights into the pathological mechanisms underlying the processing of perturbed forks. PMID- 26275777 TI - Functional interaction of Rpb1 and Spt5 C-terminal domains in co-transcriptional histone modification. AB - Transcription by RNA polymerase II (RNAPII) is accompanied by a conserved pattern of histone modifications that plays important roles in regulating gene expression. The establishment of this pattern requires phosphorylation of both Rpb1 (the largest RNAPII subunit) and the elongation factor Spt5 on their respective C-terminal domains (CTDs). Here we interrogated the roles of individual Rpb1 and Spt5 CTD phospho-sites in directing co-transcriptional histone modifications in the fission yeast Schizosaccharomyces pombe. Steady state levels of methylation at histone H3 lysines 4 (H3K4me) and 36 (H3K36me) were sensitive to multiple mutations of the Rpb1 CTD repeat motif (Y1S2P3T4S5P6S7). Ablation of the Spt5 CTD phospho-site Thr1 reduced H3K4me levels but had minimal effects on H3K36me. Nonetheless, Spt5 CTD mutations potentiated the effects of Rpb1 CTD mutations on H3K36me, suggesting overlapping functions. Phosphorylation of Rpb1 Ser2 by the Cdk12 orthologue Lsk1 positively regulated H3K36me but negatively regulated H3K4me. H3K36me and histone H2B monoubiquitylation required Rpb1 Ser5 but were maintained upon inactivation of Mcs6/Cdk7, the major kinase for Rpb1 Ser5 in vivo, implicating another Ser5 kinase in these regulatory pathways. Our results elaborate the CTD 'code' for co transcriptional histone modifications. PMID- 26275778 TI - NUFIP and the HSP90/R2TP chaperone bind the SMN complex and facilitate assembly of U4-specific proteins. AB - The Sm proteins are loaded on snRNAs by the SMN complex, but how snRNP-specific proteins are assembled remains poorly characterized. U4 snRNP and box C/D snoRNPs have structural similarities. They both contain the 15.5K and proteins with NOP domains (PRP31 for U4, NOP56/58 for snoRNPs). Biogenesis of box C/D snoRNPs involves NUFIP and the HSP90/R2TP chaperone system and here, we explore the function of this machinery in U4 RNP assembly. We show that yeast Prp31 interacts with several components of the NUFIP/R2TP machinery, and that these interactions are separable from each other. In human cells, PRP31 mutants that fail to stably associate with U4 snRNA still interact with components of the NUFIP/R2TP system, indicating that these interactions precede binding of PRP31 to U4 snRNA. Knock down of NUFIP leads to mislocalization of PRP31 and decreased association with U4. Moreover, NUFIP is associated with the SMN complex through direct interactions with Gemin3 and Gemin6. Altogether, our data suggest a model in which the NUFIP/R2TP system is connected with the SMN complex and facilitates assembly of U4 snRNP-specific proteins. PMID- 26275779 TI - Comparison of Post-injection Site Pain Between Technetium Sulfur Colloid and Technetium Tilmanocept in Breast Cancer Patients Undergoing Sentinel Lymph Node Biopsy. AB - BACKGROUND: No prior studies have examined injection pain associated with Technetium-99m Tilmanocept (TcTM). METHODS: This was a randomized, double-blinded study comparing postinjection site pain between filtered Technetium Sulfur Colloid (fTcSC) and TcTM in breast cancer lymphoscintigraphy. Pain was evaluated with a visual analogue scale (VAS) (0-100 mm) and the short-form McGill Pain Questionnaire (SF-MPQ). The primary endpoint was mean difference in VAS scores at 1-min postinjection between fTcSC and TcTM. Secondary endpoints included a comparison of SF-MPQ scores between the groups at 5 min postinjection and construction of a linear mixed effects model to evaluate the changes in pain during the 5-min postinjection period. RESULTS: Fifty-two patients underwent injection (27-fTcSC, 25-TcTM). At 1-min postinjection, patients who received fTcSC experienced a mean change in pain of 16.8 mm (standard deviation (SD) 19.5) compared with 0.2 mm (SD 7.3) in TcTM (p = 0.0002). At 5 min postinjection, the mean total score on the SF-MPQ was 2.8 (SD 3.0) for fTcSC versus 2.1 (SD 2.5) for TcTM (p = 0.36). In the mixed effects model, injection agent (p < 0.001), time (p < 0.001) and their interaction (p < 0.001) were associated with change in pain during the 5-min postinjection period. The model found fTcSC resulted in significantly more pain of 15.2 mm (p < 0.001), 11.3 mm (p = 0.001), and 7.5 mm (p = 0.013) at 1, 2, and 3 min postinjection, respectively. CONCLUSIONS: Injection with fTcSC causes significantly more pain during the first 3 min postinjection compared with TcTM in women undergoing lymphoscintigraphy for breast cancer. PMID- 26275780 TI - Impact of Chemotherapy-Induced Ovarian Dysfunction on Response to Neoadjuvant Chemotherapy in Breast Cancer. AB - BACKGROUND: The association between chemotherapy-induced ovarian dysfunction (CIOD) and response to neoadjuvant chemotherapy (NAC) is not known. We therefore investigated the impact of CIOD on response to NAC in breast cancer patients according to estrogen receptor (ER) status. METHODS: In total, 343 premenopausal breast cancer patients treated with NAC between 2006 and 2010 were analyzed. Clinical responses were determined based on changes in tumor size measured using breast MRI. Patients with complete response or partial response were considered to have clinical response. RESULTS: After completion of NAC, 264 of 343 patients (76.9 %) developed CIOD. The clinical response rate was significantly higher in patients with CIOD than those without CIOD (65.2 vs. 51.9 %; p = 0.033). Additionally, the mean follicle-stimulating hormone (FSH) level after NAC was significantly higher in patients with clinical response (FSH 68.7 +/- 34.5 vs. 59.8 +/- 34.3 IU/L; p = 0.021). Multivariate analysis showed an independent association of CIOD to clinical response (OR 0.523, 95 % CI 0.297-0.918; p = 0.024). However, we observed no differences in the pathologic complete response (pCR) rate between patients with and without CIOD (8.7 vs. 6.3 %; p = 0.497). Subgroup analysis according to ER status showed that the association between CIOD and clinical response was significant in ER-positive but not ER-negative breast cancer (p = 0.025 and 0.818, respectively). CONCLUSIONS: CIOD during NAC is significantly associated with clinical response, but not pCR. Moreover, this association is only observed in ER-positive breast cancer, suggesting that the moderate difference in response to NAC is possibly a hormonal effect of chemotherapy-induced ovarian dysfunction. PMID- 26275781 TI - Evaluation of the Clinical Utility of the ICG Fluorescence Method Compared with the Radioisotope Method for Sentinel Lymph Node Biopsy in Breast Cancer. AB - PURPOSE: This study compared the clinical utility of indocyanine green (ICG) fluorescence and radioisotope (RI) for sentinel lymph node (SLN) detection in breast cancer. METHODS: Women with node-negative breast cancer underwent SLN biopsy using ICG fluorescence and RI. The primary end point was the sensitivity of ICG fluorescence compared with RI in the patients with tumor-positive SLNs. Secondary end points included detection rates for SLN, the additive effect of ICG fluorescence to RI, signature of positive SLNs according to tier, and adverse events related to ICG administration. RESULTS: A total of 847 women with clinical node-negative breast cancer underwent SLN biopsy, and 821 patients were included in the per-protocol analysis. SLN mapping was performed using ICG fluorescence and RI. The overall detection of SLNs using ICG fluorescence was identical to RI (97.2 vs. 97.0 %, P = 0.88), and the combination of both methods achieved a significant improvement compared with RI alone (99.8 vs. 97.0 %, P < 0.001). The detection rate for tumor-positive SLN was 93.3 % for ICG fluorescence and 90.0 % for RI, and the sensitivity of the ICG fluorescence method was 95.7 % (95 % CI 91.3-98.3, P = 0.11). The additional use of ICG significantly improved positive SLN detection for RI (97.2 vs. 90.0 %, P < 0.001). There were no serious adverse events related to hypersensitivity to ICG. CONCLUSIONS: The ICG fluorescence method may be an acceptable alternative to SLN detection using RI in breast cancer. PMID- 26275782 TI - Use of Medical Devices in Hospice for Symptom Management. AB - BACKGROUND: Home health services in the United States(US) have been on a rise. Hospice patients cope with diverse physical and pain symptoms; medical devices are used for symptom management to improve their quality-of-care at end-of-life. OBJECTIVE: Using the National Home and Hospice Care Survey (NHHCS), the study summarizes medical device use for symptom management and tracks various demographic variables for home hospice patients. METHODS: A cross-sectional analysis of data using the 2007 NHHCS was conducted. There were 4733 hospice discharges which corresponded to 2,505,011 individuals in US with sampling weights. The data was analyzed using chi square tests and confounding factors adjusted with logistic regression. RESULTS: Eighty-nine percent of hospice discharges were evaluated for pain at first assessment. The regression model for pain at first assessment was significantly associated with use of patient controlled analgesia (OR = 1.82, 95% CI = 1.28, 2.59) and urinary catheters (OR = 1.16, 95% CI = 1.02, 1.33). Patient with dyspnea were associated with significant use of oxygen (OR = 3.00, 95% CI = 2.64, 3.40) and metered dose inhaler (OR = 2.43, 95% CI = 1.92, 3.07). There was negligible use of total parenteral nutrition (TPN) noted in the study. CONCLUSION: In conclusion, the study highlights medical device use in home hospice care for end-of-life symptom management. It noted the significant use of IV infusion pumps and patient controlled analgesia. Conversely, there is little use of TPN or CPAP in patients with anorexia or dyspnea. While missing data on critical symptom evaluations regrettably raises questions about the validity of the study, the NHHCS serves as an important reservoir of data on the growing population of home hospice patients. PMID- 26275783 TI - Impact of a Centralized Inpatient Hospice Unit in an Academic Medical Center. AB - OBJECTIVE: Rush University Medical Center (RUMC) and Horizon Hospice opened the first centralized inpatient hospice unit (CIPU) in a Chicago academic medical center in 2012. This study examined if there was a difference in cost or length of stay (LOS) in a CIPU compared to hospice care in scattered beds throughout RUMC. STUDY DESIGN AND METHODS: This retrospective, cross-sectional study compared cost and LOS for patients admitted to the CIPU (n = 141) and those admitted to hospice scattered beds (SBM) throughout RUMC (n = 56). RESULTS: The CIPU patients had a median LOS of 6.0 days versus 2.0 days for SBM patients. CONCLUSIONS: The CIPU patients had longer hospice LOS but lower hospital costs. Academic medical centers may benefit from aggregating hospice beds. PMID- 26275784 TI - Integrating Immunotherapies in Prostate Cancer. AB - In recent years, immunotherapy has emerged as a viable and promising treatment for prostate cancer. Beyond sipulecuel-T, phase III trials are evaluating multiple vaccine and immune-based therapies in men with this disease. Evidence suggests that many of these therapies are effective at augmenting immune responses and slowing tumor growth rates. Yet prospective data evaluating these responses as surrogates for survival are still needed. In the absence of validated intermediate markers of response, growing data suggests that patients with more indolent disease are more likely to benefit from immunotherapies. In order to further optimize immunotherapy use, ongoing trials are evaluating its combination with traditional as well as other immune-based treatments. Preliminary data from these trials are promising and are shedding new light on this area. PMID- 26275785 TI - Breaks in Play: Do They Achieve Intended Aims? AB - Breaks in play represent a responsible gambling strategy designed to disrupt states of dissociation and enhance the likelihood of drawing attention to a player's session behaviour and expenditure with respect to time and money. The aim of the break in play is to motivate the player to modify or cease gambling so the activity remains within affordable levels. The aim of this study was to investigate whether imposed breaks in play in the absence of accompanying warning messages were effective in reducing cravings. Participants (141 university students) were randomly allocated to one of three conditions: 15 min computer simulated Black Jack play followed by no break, a 3 or 8 min break in play. Participants were administered a battery of measures to assess problem gambling card play, cravings, and dissociation to assess the effects of length of break on cravings. Results indicated that cravings increased rather than decreased with imposed breaks in play, and that the strength of cravings were higher following the eight- compared to 3-min break. It was concluded that breaks in play in isolation might produce counterproductive, unintended, and even perverse effects. The policy implications for responsible gambling strategies is that breaks in play ought to be accompanied with warning and/or personal appraisal messages if optimal effects in reducing within session gambling expenditure are to be achieved. PMID- 26275786 TI - Low levels of CD9 coincidental with a novel nonsense mutation in glycoprotein Ibbeta in a patient with Bernard-Soulier syndrome. PMID- 26275787 TI - Effects of age on arterial stiffness and central blood pressure after an acute bout of resistance exercise. AB - PURPOSE: To investigate the influence of age on arterial stiffness and blood pressure after performing a resistance exercise bout. METHODS: Recreationally active men were separated into young (YG, n = 12, 26.5 +/- 3.3 years), middle (MG, n = 14, 49.4 +/- 5.7 years), and old (OG, n = 10, 67.4 +/- 6.3 years)-aged groups. In a randomized cross-over design, participants performed control and exercise conditions with at least 3 days separating conditions. The exercise condition consisted of leg press, chest press, knee flexion, lat pulldown and knee extension at ~65% one-repetition maximum for three sets of 10 repetitions. Brachial and central blood pressures, augmented pressure, augmentation index, central and peripheral pulse wave velocities were measured prior to each condition and starting at 5 min post-exercise. RESULTS: Brachial systolic blood pressure (SBP) significantly increased similarly after exercise for all age groups (YG, 8 +/- 8 mmHg; MG, 5 +/- 5 mmHg; OG, 5 +/- 6 mmHg; p < 0.05). However, central SBP did not significantly increase for any age group after exercise. Augmentation index significantly increased after exercise only in the YG (11 +/- 8%, p < 0.05). Central pulse wave velocity did not significantly increase in any age group after exercise when compared to the control condition. CONCLUSIONS: When performing a whole body moderate resistance exercise bout, acute changes in arterial stiffness and blood pressure appear to be minimally affected by age. PMID- 26275788 TI - The real cost of care: focus on value for money, rather than price-tags. PMID- 26275790 TI - Association Between the Use of Oral Contraceptives and Patient-Reported Outcomes in an Early Arthritis Cohort. AB - OBJECTIVE: To evaluate the association between exposure to oral contraceptives (OCs) and clinical outcomes in an early arthritis cohort. METHODS: Female patients with early inflammatory arthritis, ages 18-60 years, who were enrolled in an early arthritis cohort and had no exposure to hormone replacement were studied (n = 273). Associations between OC exposure (current/past/never) and disease activity, treatment, and patient-reported outcomes, including the Rheumatoid Arthritis Impact of Disease Score (RAID), the Rheumatoid Arthritis Disease Activity Index (RADAI), the Profile of Mood and Discomfort (PROFAD), and the Hannover Functional Assessment (FFbH), were studied over 2 years. Linear mixed models adjusted for age, body mass index, parity, smoking, and education were used. RESULTS: Eighteen percent of patients had never used OCs, 63% had used OCs in the past, and 19% currently used OCs. After adjustment, the current/past OC use was associated with better RAID, PROFAD, RADAI, and FFbH scores at 12 months (P < 0.05 for all) compared to never use. Longitudinally over 2 years, the mean RAID scores were significantly better in women with current/past OC use (P < 0.001). Actual inflammatory markers were not associated with OC use. Glucocorticoids were used by a higher percentage of OC never users than by current/past users (P = 0.08), especially in patients with impaired function (FFbH <70: odds ratio 4.2 [95% confidence interval 1.6-11]). CONCLUSION: For past as well as current use, OCs seem to moderate patient-reported outcomes in inflammatory arthritis. Protective effects may be induced via central nervous pathways rather than through the suppression of peripheral inflammation. PMID- 26275791 TI - Lutibacter holmesii sp. nov., a marine bacterium of the family Flavobacteriaceae isolated from the sea urchin Strongylocentrotus intermedius, and emended description of the genus Lutibacter. AB - Seven Gram-staining-negative, strictly aerobic, pale-yellow-pigmented, rod-shaped and non-motile strains were isolated from the sea urchin Strongylocentrotus intermedius collected from Troitsa Bay, Sea of Japan. Phylogenetic analyses based on 16S rRNA gene sequences showed that these isolates were affiliated with the family Flavobacteriaceae. The novel isolates showed 99.9-100 % 16S rRNA gene sequence similarity to each other and were closely related to the type strains of the recognized members of the genus Lutibacter with sequence similarities of 95.8 98.4 %. The G+C content of the genomic DNA was 35-36 mol%. DNA-DNA relatedness among the sea urchin isolates was 95-99 % and between strain KMM 6277T and its most closely related type strains, Lutibacter agarilyticus KCTC 23842T and Lutibacter litoralis JCM 13034T, was 38 and 27 %, respectively. The prevalent fatty acids were iso-C15 : 0, anteiso-C15 : 0, summed feature 3 (comprising iso C15 : 0 2-OH and/or C16 : 1 omega7c fatty acids), iso-C15 : 1 and C15 : 0. The polar lipid profile was composed of the phosphatidylethanolamine, one unknown aminolipid and one unknown lipid. The main respiratory isoprenoid quinone was MK 6.The results of phylogenetic, phenotypic and genotypic analyses indicated that the novel strains represent a novel species within the genus Lutibacter, for which the name Lutibacter holmesii sp. nov. is proposed. The type strain is KMM 6277T ( = CCUG 62221T = LMG 26737T). PMID- 26275789 TI - Bone metastasis and the metastatic niche. AB - The bone marrow has been long known to host a unique environment amenable to colonization by metastasizing tumor cells. Yet, the underlying molecular interactions within this specialized microenvironment which give rise to the high incidence of bone metastasis in breast and prostate cancer patients have long remained uncharacterized. With the recent description of the bone metastatic "niche," considerable focus has been placed on understanding how the bone stroma contributes to each step of metastasis. Discoveries within this field have demonstrated that when cancer cells home to the niche in which hematopoietic and mesenchymal stem/progenitor cells normally reside, a bidirectional crosstalk emerges between the tumor cells and the bone metastatic stroma. This communication modulates every step of cancer cell metastasis to the bone, including the initial homing and seeding, formation of micrometastases, outgrowth of macrometastases, and the maintenance of long-term dormancy of disseminated tumor cells in the bone. In clinical practice, targeting the bone metastatic niche is evolving into a promising avenue for the prevention of bone metastatic relapse, therapeutic resistance, and other aspects of cancer progression. Here, we review the current knowledge concerning the role of the bone metastatic niche in bone metastasis. PMID- 26275792 TI - Atypical pyogenic brain abscess evaluation by diffusion-weighted imaging: diagnosis with multimodality MR imaging. AB - Whether a brain abscess is apparent by imaging depends on the stage of the abscess at the time of imaging, as well as the etiology of the infection. Because conventional magnetic resonance imaging (MRI) is limited in its ability to distinguish brain abscesses from necrotic tumors, advanced techniques are required. The management of these two disease entities differs and can potentially affect the clinical outcome. We report a case having atypical imaging features of a pyogenic brain abscess on advanced MRI, in particular, on diffusion weighted and perfusion imaging, in a patient with osteosarcoma undergoing chemotherapy. PMID- 26275793 TI - Reproductive genetic counseling challenges associated with diagnostic exome sequencing in a large academic private reproductive genetic counseling practice. AB - OBJECTIVE: Diagnostic whole exome sequencing (WES) is rapidly entering clinical genetics, but experience with reproductive genetic counseling aspects is limited. The purpose of this study was to retrospectively review and report on our experience with preconception and prenatal genetic counseling for diagnostic WES. METHOD: We performed a retrospective chart review over 34 months in a large private prenatal genetic counseling practice and analyzed data for referral indications, findings, and results of genetic counseling related to diagnostic WES. RESULTS: Ten of 14 patients counseled about diagnostic WES for ongoing pregnancies pursued the test, resulting in identification of three pathogenic variants (30%). Five of 15 patients seeking counseling about familial WES results in an affected proband pursued prenatal diagnosis, resulting in identification of one affected fetus and five unaffected fetuses. We experienced challenges related to complexity and uncertainty of results, turnaround time, cost and insurance overage, and multidisciplinary fetal care coordination. CONCLUSION: Despite having experienced complexity and identified challenges of the reproductive genetic counseling, availability of diagnostic WES contributed important information that aided in prenatal care planning and decision-making. Future enhanced provider education and larger studies to systematically study the integration of WES in reproductive genetic counseling and prenatal care will be important. PMID- 26275795 TI - Vaccines, adjuvants and autoimmunity. AB - Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future. PMID- 26275794 TI - Therapeutic potential of chemokine signal inhibition for metastatic breast cancer. AB - Metastatic breast cancer is incurable by current therapies including chemotherapy and immunotherapy. Accumulating evidence indicates that tumor-infiltrating macrophages promote establishment of the lethal metastatic foci and contribute to therapeutic resistance. Recent studies suggest that the accumulation of these macrophages is regulated by a chemokine network established in the tumor microenvironment. In this perspective paper, we elaborate on the chemokine signals that can attract monocytes/macrophages to the site of metastasis, and discuss whether inhibition of these chemokine signals can represent a new therapeutic strategy for metastatic breast cancer. PMID- 26275796 TI - Clinical characteristics of patients with lower limb cellulitis and antibiotic usage in Hospital Kuala Lumpur: a 7-year retrospective study. AB - BACKGROUND: Cellulitis commonly involved lower limbs. This study was carried out to determine the demography, clinical characteristics, risk factors, microbiological aspects, and antibiotics usage in this group of patients in Hospital Kuala Lumpur. METHODS: A total of one hundred and twenty four patients with lower limb cellulitis treated in the Department of Dermatology, Hospital Kuala Lumpur, between January 2008 and May 2013 were included in this study. RESULTS: There were 70 male and 54 female patients, aged between 13 and 87 years (mean 57.23+/-12.854). Thirty-one of them (25%) had recurrent cellulitis. Fifty seven (46%) had fever at presentation, 55 (44.4%) had bullous cellulitis. The top risk factors identified were toe web intertrigo (n = 79, 63.7%), hypertension (n=76, 61.3%), obesity (n = 55, 44.4%), and diabetes (n = 55, 44.4%). However, only toe web intertrigo (p = 0.003), peripheral vascular disease (p = 0.01), and varicose veins (p = 0.02) were significantly higher in recurrent cellulitis. Thirty patients (24.2%) were complicated with lipodermatosclerosis, and six (4.8%) had lymphostasis verrucosa cutis. Skin swab cultures were positive in 54 (43.5%) patients, and Pseudomonas sp. was the most frequently identified organism. Mean number of antibiotics given for one episode of cellulitis was 1.7+/-1. The antibiotics most given were cloxacillin (n=57, 46%) and other penicillins (n = 71, 57%), followed by cephalosporins (n = 40, 32%). CONCLUSION: Identifying clinical characteristics of those at risk may help to prevent recurrence of cellulitis and long-term complications. PMID- 26275797 TI - A multi-criteria analysis of options for energy recovery from municipal solid waste in India and the UK. AB - Energy recovery from municipal solid waste plays a key role in sustainable waste management and energy security. However, there are numerous technologies that vary in suitability for different economic and social climates. This study sets out to develop and apply a multi-criteria decision making methodology that can be used to evaluate the trade-offs between the benefits, opportunities, costs and risks of alternative energy from waste technologies in both developed and developing countries. The technologies considered are mass burn incineration, refuse derived fuel incineration, gasification, anaerobic digestion and landfill gas recovery. By incorporating qualitative and quantitative assessments, a preference ranking of the alternative technologies is produced. The effect of variations in decision criteria weightings are analysed in a sensitivity analysis. The methodology is applied principally to compare and assess energy recovery from waste options in the UK and India. These two countries have been selected as they could both benefit from further development of their waste-to energy strategies, but have different technical and socio-economic challenges to consider. It is concluded that gasification is the preferred technology for the UK, whereas anaerobic digestion is the preferred technology for India. We believe that the presented methodology will be of particular value for waste-to-energy decision-makers in both developed and developing countries. PMID- 26275798 TI - Mock-up experiment at Birmingham University for BNCT project of Osaka University- Neutron flux measurement with gold foil. AB - Mock-up experiment for development of accelerator based neutron source for Osaka University BNCT project was carried out at Birmingham University, UK. In this paper, spatial distribution of neutron flux intensity was evaluated by foil activation method. Validity of the design code system was confirmed by comparing measured gold foil activities with calculations. As a result, it was found that the epi-thermal neutron beam was well collimated by our neutron moderator assembly. Also, the design accuracy was evaluated to have less than 20% error. PMID- 26275799 TI - Pokeweed antiviral protein restores levels of cellular APOBEC3G during HIV-1 infection by depurinating Vif mRNA. AB - Pokeweed antiviral protein (PAP) is an RNA glycosidase that inhibits production of human immunodeficiency virus type 1 (HIV-1) when expressed in human culture cells. Previously, we showed that the expression of PAP reduced the levels of several viral proteins, including virion infectivity factor (Vif). However, the mechanism causing Vif reduction and the consequences of the inhibition were not determined. Here we show that the Vif mRNA is directly depurinated by PAP. Because of depurination at two specific sites within the Vif ORF, Vif levels decrease during infections and the progeny viruses that are generated are ~ 10 fold less infectious and compromised for proviral integration. These results are consistent with PAP activity inhibiting translation of Vif, which in turn reduces the effect of Vif to inactivate the host restriction factor APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like editing complex 3G). Our findings identify Vif mRNA as a new substrate for PAP and demonstrate that derepression of innate immunity against HIV-1 contributes to its antiviral activity. PMID- 26275800 TI - Hepatitis delta virus: From biological and medical aspects to current and investigational therapeutic options. AB - An estimated 15-20 million individuals are co-infected by hepatitis B and hepatitis D virus worldwide and are at high risk of developing end-stage liver disease, including hepatocellular carcinoma. While HBV viremia can now be controlled in the vast majority of individuals by nucleoside analogs, leading to a delay of disease progression, HDV treatment has for long relied on the relatively inefficient and not well-tolerated interferon-alpha. While the epidemiology and pathogenesis of the disease remain to be precisely determined, using adequate diagnostic tools and well-designed cohort studies, basic research efforts have led to interesting progress in the understanding of HDV biology, which is not yet sufficient to identify specific antiviral targets. More resources now need to be devoted to the HDV field to achieve therapeutic breakthroughs. In this manuscript, we carefully review the literature regarding the biology of hepatitis D virus, the disease, its prevention, current treatments and investigational strategies. This article forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for chronic hepatitis B." PMID- 26275801 TI - Immune-modulators to combat hepatitis B virus infection: From IFN-alpha to novel investigational immunotherapeutic strategies. AB - Chronic hepatitis B virus (HBV) infection remains a major challenge for clinicians, as there are only two types of approved therapies: interferon-alpha (IFN-alpha) or its pegylated form, Peg-IFN-alpha and nucleoside analogs (e.g. tenofovir, entecavir...). The first are used as finite-duration treatments of around 48-52 weeks, while the second must be taken life-long to prevent rebound. Other immune-modulators, including other types of recombinant IFNs and cytokines/chemokines, could be developed for treating chronic hepatitis B. Alternatively, strategies aimed either at restoring or favoring the endogenous production of IFNs, cytokines and/or chemokines, or at alleviating HBV-mediated inhibitory processes could also be envisaged. In this article, we review current investigational, preclinical and clinical efforts to implement immune-modulatory components in the therapy of chronic hepatitis B. This review forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for hepatitis B". PMID- 26275802 TI - Conservation of antiviral activity and improved selectivity in PMEO-DAPym upon pyrimidine to triazine scaffold hopping. AB - Acyclic nucleoside phosphonates incorporating 2,4-diaminotriazine (DAT) as a 5 aza-analog of the 2,4-diamino-pyrimidine (DAPym) nucleobase present in PMEO DAPyms have been synthesized. The lead PMEO-DAT is as inhibitory against HIV, HBV, MSV and VZV replication as the parent PMEO-DAPym and equally inefficient at markedly affecting replication of HSV-1, HSV-2 and HCMV. A rationale for this similar biological profile is proposed on the basis of structural differences in the active site of the viral DNA polymerases. PMEO-DAT is, however, more selective because, unlike PMEO-DAPym, it does not stimulate secretion of beta chemokines in cultured PBMC. PMID- 26275803 TI - Equine herpesvirus-1 suppresses type-I interferon induction in equine endothelial cells. AB - Equine herpesvirus-1 (EHV-1) is one of the most common and important respiratory viral pathogens of horses. EHV-1 in horses replicates initially in the respiratory epithelium and then spreads systematically to endothelial cells lining the small blood vessels in the uterus and spinal cord, and highly pathogenic virus strains can produce aborted fetuses or myeloencephalopathy. Like other herpes viruses, EHV-1 employs a variety of mechanisms for immune evasion. Some herpes viruses down-regulate the type-I interferon (IFN) response to infection, but such activity has not been described for EHV-1. Here, in an in vitro system utilizing an established equine endothelial cell line, we studied the temporal effect on IFN-beta responses following infection with the neuropathogenic T953 strain of EHV-1. Results show that after an early induction of IFN-beta, the virus actively shut down further production of IFN-beta and this was correlated with expression of the viral late genes. Expression of the IFN response factor viperin, a marker of host cell type-I IFN responses, was also suppressed by T953 virus infection. EHV-1-mediated suppression of host type-I IFN responses may play an important role in EHV-1 pathogenesis and the mechanism of this, presumably involving a viral late gene product, warrants investigation. PMID- 26275804 TI - Prospective clinical study of R-CMD therapy for indolent B cell lymphoma and mantle cell lymphoma from the Hokuriku Hematology Oncology Study Group. AB - Standardized treatments for indolent B cell lymphoma primarily consisting of follicular lymphoma (FL) and for mantle cell lymphoma (MCL) have yet to be established. Here the Hokuriku Hematology Oncology Study Group conducted a multicenter prospective study to investigate the efficacy and safety of a combination regimen of rituximab, cladribine, mitoxantrone, and dexamethasone (R CMD) in indolent B cell lymphoma and MCL. A total of 33 CD20-positive patients who received care between January 2008 and August 2011 were investigated. These patients' illnesses were FL (n = 21), nodal marginal zone B cell lymphoma (NMZB, n = 3), MCL (n = 3), splenic marginal zone B cell lymphoma (n = 2), hairy cell leukemia (n = 1), Waldenstrom macroglobulinemia (WM, n = 1), and lymphoplasmacytic lymphoma (LPL, n = 2). Patients received four 21-day cycles of rituximab 375 mg/m(2) (day 1), cladribine 0.10 mg/kg (days 1-3), mitoxantrone 8 mg/m(2) (day 1), and dexamethasone 8 mg/body (days 1-3), with four additional rituximab doses at 4-week intervals. Of the 33 patients, 26 achieved complete response/unconfirmed complete response, and six achieved a partial response (4 with FL, 1 with NMZB, 1 with WM). One had progressive disease (FL), and four relapsed after remission (1 with FL, 2 with MCL, 1 with LPL). R-CMD therapy was relatively convenient and effective in indolent B cell lymphoma and MCL. Nonetheless, to suppress the number and function of both B cells and T cells, comprehensive infection prevention and follow-up are necessary in the future. PMID- 26275805 TI - A crystal structure of 2-hydroxybiphenyl 3-monooxygenase with bound substrate provides insights into the enzymatic mechanism. AB - 2-Hydroxybiphenyl 3-monooxygenase (HbpA) is an FAD dependent monooxygenase which catalyzes the ortho-hydroxylation of a broad range of 2-substituted phenols in the presence of NADH and molecular oxygen. We have determined the structure of HbpA from the soil bacterium Pseudomonas azelaica HBP1 with bound 2 hydroxybiphenyl, as well as several variants, at a resolution of 2.3-2.5A to investigate structure function correlations of the enzyme. An observed hydrogen bond between 2-hydroxybiphenyl and His48 in the active site confirmed the previously suggested role of this residue in substrate deprotonation. The entrance to the active site was confirmed by generating variant G255F which exhibited only 7% of the wild-type's specific activity of product formation, suggesting inhibition of substrate entrance into the active site by the large aromatic residue. Residue Arg242 is suggested to facilitate FAD movement and reduction as was previously reported in studies on the homologous protein para hydroxybenzoate hydroxylase. In addition, it is suggested that Trp225, which is located in the active site, facilitates proper substrate entrance into the binding pocket in contrast to aklavinone-11-hydroxylase and para-hydroxybenzoate hydroxylase in which a residue at a similar position is responsible for substrate deprotonation. Structure function correlations described in this work will aid in the design of variants with improved activity and altered selectivity for potential industrial applications. PMID- 26275806 TI - Structure of decorin binding protein B from Borrelia burgdorferi and its interactions with glycosaminoglycans. AB - Decorin-binding proteins (DBPs), DBPA and DBPB, are surface lipoproteins on Borrelia burgdorferi, the causative agent of Lyme disease. DBPs bind to the connective tissue proteoglycan decorin and facilitate tissue colonization by the bacterium. Although structural and biochemical properties of DBPA are well understood, little is known about DBPB. In current work, we determined the solution structure of DBPB from strain B31 of B. burgdorferi and characterized its interactions with glycosaminoglycans (GAGs). Our structure shows that DBPB adopts the same topology as DBPA, but possesses a much shorter terminal helix, resulting in a longer unstructured C-terminal tail, which is also rich in basic amino acids. Characterization of DBPB-GAG interactions reveals that, despite similar GAG affinities of DBPA and DBPB, the primary GAG-binding sites in DBPB are different from DBPA. In particular, our results indicate that lysines in the C-terminus of DBPB are vital to DBPB's ability to bind GAGs whereas C-terminal tail for DBPA from strain B31 only plays a minor role in facilitating GAG bindings. Furthermore, the traditional GAG-binding pocket important to DBPA-GAG interactions is only secondary to DBPB's GAG-binding ability. PMID- 26275807 TI - Inactivation of the particulate methane monooxygenase (pMMO) in Methylococcus capsulatus (Bath) by acetylene. AB - Acetylene (HCCH) has a long history as a mechanism-based enzyme inhibitor and is considered an active-site probe of the particulate methane monooxygenase (pMMO). Here, we report how HCCH inactivates pMMO in Methylococcus capsulatus (Bath) by using high-resolution mass spectrometry and computational simulation. High resolution MALDI-TOF MS of intact pMMO complexes has allowed us to confirm that the enzyme oxidizes HCCH to the ketene (C2H2O) intermediate, which then forms an acetylation adduct with the transmembrane PmoC subunit. LC-MS/MS analysis of the peptides derived from in-gel proteolytic digestion of the protein subunit identifies K196 of PmoC as the site of acetylation. No evidence is obtained for chemical modification of the PmoA or PmoB subunit. The inactivation of pMMO by a single adduct in the transmembrane PmoC domain is intriguing given the complexity of the structural fold of this large membrane-protein complex as well as the complicated roles played by the various metal cofactors in the enzyme catalysis. Computational studies suggest that the entry of hydrophobic substrates to, and migration of products from, the catalytic site of pMMO are controlled tightly within the transmembrane domain. Support of these conclusions is provided by parallel experiments with two related alkynes: propyne (CH3CCH) and trifluoropropyne (CF3CCH). Finally, we discuss the implication of these findings to the location of the catalytic site in pMMO. PMID- 26275808 TI - The Role of CXC Chemokines in Pulmonary Fibrosis of Systemic Lupus Erythematosus Patients. AB - The inflammatory process in systemic lupus erythematosus (SLE) affects many organs including the lungs. CXC chemokines are suggested to play an important role in the pathogenesis of SLE and pulmonary fibrosis. To estimate the concentrations of CXCL9, CXCL10, CXCL11 in bronchoalveolar lavage fluid (BALF) of patients with and without pulmonary involvements of SLE to evaluate CXC chemokines role in the pathogenesis of pulmonary fibrosis in SLE. Twenty-six SLE patients and 31 healthy controls were evaluated using high-resolution computed tomography (HRCT), pulmonary function tests, the SLE Disease Activity Index (SLEDAI), assessing CXCL9, CXCL11, CXCL10 level in BALF (an enzyme-immunosorbent assay kit). The mean CXCL9 and CXCL11 concentrations in BALF were higher in SLE patients compared to healthy controls (34.09 +/- 102.34 vs 10.98 +/- 14.65 pg/mL, p < 0.001; 72.65 +/- 112.89 vs 16.12 +/- 83.75 pg/mL, p = 0.012, respectively). The disease activity scored by SLEDAI and the concentration of CXCL10 in BALF were significantly higher in the SLE patients with pulmonary fibrosis when compared with patients with normal HRCT (8.23 +/- 3.19 vs 5.01 +/- 2.41; 73.45 +/ 34.12 vs 40.76 +/- 41.65, respectively, in both p < 0.05). In SLE patients positive correlations were found between SLEDAI and the percentage of lymphocytes in BALF (r = 0.51, p < 0.05); CXCL9 and CXCL10 concentrations in BALF (r = 0.65, p < 0.001); CXCL9 and CXCL11 concentrations in BALF (r = 0.69, p < 0.001). In lupus patients with pulmonary manifestations positive correlations were found between CXCL11 concentration in BALF and SLEDAI (r = 0.55, p < 0.05), CXCL11 concentration and the percentage of neutrophils in BALF (r = 0.69, p < 0.05), CXCL10 concentration and the percentage of neutrophils in BALF (r = 0.57, p < 0.05). Our observations indicate that CXCL9 and CXCL11 play an important role in the pathogenesis of SLE but it needs further studies. These results suggest that CXCL10 and CXCL11 are associated with neutrophils accumulation in the alveolar space of SLE patients with pulmonary fibrosis and should be considered as potential factor of interstitial fibrosis. PMID- 26275809 TI - Cooperative hand movements in post-stroke subjects: Neural reorganization. AB - OBJECTIVE: Recent research indicates a task-specific neural coupling controlling cooperative hand movements reflected in bilateral electromyographic reflex responses in arm muscles following unilateral nerve stimulation. Reorganization of this mechanism was explored in post-stroke patients in this study. METHODS: Electromyographic reflex responses in forearm muscles to unilateral electrical ulnar nerve stimulation were examined during cooperative and non-cooperative hand movements. RESULTS: Stimulation of the unaffected arm during cooperative hand movements led to electromyographic responses in bilateral forearm muscles, similar to those seen in healthy subjects, while stimulation of the affected side was followed only by ipsilateral responses. No contralateral reflex responses could be evoked in severely affected patients. The presence of contralateral responses correlated with the clinical motor impairment as assessed by the Fugl Meyer test. CONCLUSION: The observations suggest that after stroke an impaired processing of afferent input from the affected side leads to a defective neural coupling and is associated with a greater involvement of fiber tracts from the unaffected hemisphere during cooperative hand movements. SIGNIFICANCE: The mechanism of neural coupling underlying cooperative hand movements is shown to be defective in post-stroke patients. The neural re-organizations observed have consequences for the rehabilitation of hand function. PMID- 26275810 TI - Genome-wide analysis of human constitutive androstane receptor (CAR) transcriptome in wild-type and CAR-knockout HepaRG cells. AB - The constitutive androstane receptor (CAR) modulates the transcription of numerous genes involving drug metabolism, energy homeostasis, and cell proliferation. Most functions of CAR however were defined from animal studies. Given the known species difference of CAR and the significant cross-talk between CAR and the pregnane X receptor (PXR), it is extremely difficult to decipher the exact role of human CAR (hCAR) in gene regulation, relying predominantly on pharmacological manipulations. Here, utilizing a newly generated hCAR-knockout (KO) HepaRG cell line, we carried out RNA-seq analysis of the global transcriptomes in wild-type (WT) and hCAR-KO HepaRG cells treated with CITCO, a selective hCAR agonist, phenobarbital (PB), a dual activator of hCAR and hPXR, or vehicle control. Real-time PCR assays in separate experiments were used to validate RNA-seq findings. Our results indicate that genes encoding drug metabolizing enzymes are among the main clusters altered by both CITCO and PB. Specifically, CITCO significantly changed the expression of 135 genes in an hCAR dependent manner, while PB altered the expression of 227 genes in WT cells of which 94 were simultaneously modulated in both cell lines reflecting dual effects of PB on hCAR/PXR. Notably, we found that many genes promoting cell proliferation and tumorigenesis were up-regulated in hCAR-KO cells, suggesting that hCAR may play an important role in cell growth that differs from mouse CAR. Together, our results reveal both novel and known targets of hCAR and support the role of hCAR in maintaining the homeostasis of metabolism and cell proliferation in the liver. PMID- 26275812 TI - The Relationship Between Apraxia of Speech and Oral Apraxia: Association or Dissociation? AB - Acquired apraxia of speech (AOS) is a motor speech disorder that affects the implementation of articulatory gestures and the fluency and intelligibility of speech. Oral apraxia (OA) is an impairment of nonspeech volitional movement. Although many speakers with AOS also display difficulties with volitional nonspeech oral movements, the relationship between the 2 conditions is unclear. This study explored the relationship between speech and volitional nonspeech oral movement impairment in a sample of 50 participants with AOS. We examined levels of association and dissociation between speech and OA using a battery of nonspeech oromotor, speech, and auditory/aphasia tasks. There was evidence of a moderate positive association between the 2 impairments across participants. However, individual profiles revealed patterns of dissociation between the 2 in a few cases, with evidence of double dissociation of speech and oral apraxic impairment. We discuss the implications of these relationships for models of oral motor and speech control. PMID- 26275811 TI - Farnesol activates the intrinsic pathway of apoptosis and the ATF4-ATF3-CHOP cascade of ER stress in human T lymphoblastic leukemia Molt4 cells. AB - In this study, we demonstrate that treatment of T lymphoblastic leukemic Molt4 cells with farnesol activates the apoptosome via the intrinsic pathway of apoptosis. This induction was associated with changes in the level of intracellular potassium and calcium, the dissipation of the mitochondrial and plasma membrane potential, release of cytochrome c, activation of several caspases, and PARP cleavage. The induction of apoptosis by farnesol was inhibited by the addition of the pan-caspase inhibitor Z-VAD-fmk and by the exogenous expression of the anti-apoptotic protein Bcl2. Analysis of the gene expression profiles by microarray analysis revealed that farnesol increased the expression of several genes related to the unfolded protein response (UPR), including CHOP and CHAC1. This induction was associated with the activation of the PERK eIF2alpha-ATF3/4 cascade, but not the XBP-1 branch of the UPR. Although farnesol induced activation of the ERK1/2, p38, and JNK pathways, inhibition of these MAPKs had little effect on farnesol-induced apoptosis or the induction of UPR related genes. Our data indicate that the induction of apoptosis in leukemic cells by farnesol is mediated through a pathway that involves activation of the apoptosome via the intrinsic pathway and induction of the PERK-eIF2alpha-ATF3/4 cascade in a manner that is independent of the farnesol-induced activation of MAPKs. PMID- 26275813 TI - 2,3,7,8-Tetrachlorodibenzo-p-dioxin differentially suppresses angiogenic responses in human placental vein and artery endothelial cells. AB - Placental angiogenesis is dramatically increased during pregnancy in association with the elevated placental blood flows to support the rapidly growing fetus. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental toxicant and a ligand of aryl hydrocarbon receptor (AhR). Herein, we investigated the effects of TCDD on proliferation, migration, and viability of fetoplacental endothelial cells in response to a complete growth medium which contained serum and growth supplement using human umbilical cord vein (HUVECs) and artery (HUAECs) cells as models. We found that TCDD dose- and time-dependently inhibited (p < 0.05) proliferation of HUVECs and HUAECs. Treatment with TCDD at 10 nM for 6 days inhibited (p < 0.05) migration (by ~ 30%) of HUAECs, but not HUVECs. TCDD at 10nM also decreased (p < 0.05) viability of HUVECs and HUAECs. Interestingly, specific AhR siRNA blocked (p < 0.05) the TCDD-inhibited cellular responses in HUAECs, but not HUVECs. Nonetheless, TCDD at 10nM neither affected the cell cycle progression, nor did it induce cell apoptosis in HUVECs and HUAECs. In addition, TCDD at 10 nM also did not alter activation of ERK1/2 and AKT1 in HUVECs and HUAECs. Collectively, TCDD suppresses proliferation and/or migration (two key steps of angiogenesis) of HUVECs and HUAECs independent and dependent of AhR, respectively. These data suggest that TCDD inhibited growth of HUVECs and HUAECs via decreasing cell viability. Thus, TCDD may inhibit fetoplacental angiogenesis, leading to negative pregnancy outcomes. PMID- 26275814 TI - The effect of PON1 enhancers on reducing acetylcholinesterase inhibition following organophosphate anticholinesterase exposure in rats. AB - Novel nucleophiles, a series of substituted phenoxyalkyl pyridinium oximes, have been previously shown by our laboratories to enhance in vitro paraoxonase 1 (PON1)-mediated degradation of a sarin surrogate (nitrophenyl isopropyl methylphosphonate, NIMP) and a VX surrogate (nitrophenyl ethyl methylphosphonate, NEMP). Five of the most efficacious of these nucleophiles were tested in rats for their ability to reduce the level of acetylcholinesterase (AChE) inhibition in brain and peripheral tissues following exposure to NIMP or NEMP. Following simultaneous administration of a nucleophile plus surrogate (at 3 dosages yielding about 10-50% AChE inhibition in the brain at 15 min), all five nucleophiles reduced the AChE inhibition in the brain at all 3 dosages, and reduced peripheral AChE inhibition at the lowest dosage. Protective effects were seen for only a short period of time, i.e., 15 min. Even though these nucleophiles are oximes, they are not effective AChE reactivators so it is unlikely that the resultant decreases in AChE inhibition are from appreciable AChE reactivation. It is likely that the protective effects seen are, at least in part, the result of enhancement of PON1-mediated surrogate degradation, an unprecedented mechanism of therapy that has the potential to be developed into a nerve agent countermeasure. PMID- 26275816 TI - Basalt identification by interpreting nuclear and electrical well logging measurements using fuzzy technique (case study from southern Syria). AB - Fuzzy analysis technique is proposed in this research for interpreting the combination of nuclear and electrical well logging data, which include natural gamma ray, density and neutron-porosity, while the electrical well logging include long and short normal. The main objective of this work is to describe, characterize and establish the lithology of the large extended basaltic areas in southern Syria. Kodana well logging measurements have been used and interpreted for testing and applying the proposed technique. The established lithological cross section shows the distribution and the identification of four kinds of basalt, which are hard massive basalt, hard basalt, pyroclastic basalt and the alteration basalt products, clay. The fuzzy analysis technique is successfully applied on the Kodana well logging data, and can be therefore utilized as a powerful tool for interpreting huge well logging data with higher number of variables required for lithological estimations. PMID- 26275815 TI - Evolutionary patchwork of an insecticidal toxin shared between plant-associated pseudomonads and the insect pathogens Photorhabdus and Xenorhabdus. AB - BACKGROUND: Root-colonizing fluorescent pseudomonads are known for their excellent abilities to protect plants against soil-borne fungal pathogens. Some of these bacteria produce an insecticidal toxin (Fit) suggesting that they may exploit insect hosts as a secondary niche. However, the ecological relevance of insect toxicity and the mechanisms driving the evolution of toxin production remain puzzling. RESULTS: Screening a large collection of plant-associated pseudomonads for insecticidal activity and presence of the Fit toxin revealed that Fit is highly indicative of insecticidal activity and predicts that Pseudomonas protegens and P. chlororaphis are exclusive Fit producers. A comparative evolutionary analysis of Fit toxin-producing Pseudomonas including the insect-pathogenic bacteria Photorhabdus and Xenorhadus, which produce the Fit related Mcf toxin, showed that fit genes are part of a dynamic genomic region with substantial presence/absence polymorphism and local variation in GC base composition. The patchy distribution and phylogenetic incongruence of fit genes indicate that the Fit cluster evolved via horizontal transfer, followed by functional integration of vertically transmitted genes, generating a unique Pseudomonas-specific insect toxin cluster. CONCLUSIONS: Our findings suggest that multiple independent evolutionary events led to formation of at least three versions of the Mcf/Fit toxin highlighting the dynamic nature of insect toxin evolution. PMID- 26275817 TI - Polymer gel dosimeter based on itaconic acid. AB - A new polymeric dosimeter based on itaconic acid and N, N'-methylenebisacrylamide was studied. The preparation method, compositions of monomer and crosslinking agent and the presence of oxygen in the dosimetric system were analyzed. The resulting materials were irradiated with an X-ray tube at 158cGy/min, 226cGymin and 298cGy/min with doses up to 1000Gy. The dosimeters presented a linear response in the dose range 75-1000Gy, sensitivities of 0.037 1/Gyat 298cGy/min and an increase in the sensitivity with lower dose rates. One of the most relevant outcomes in this study was obtaining different monomer to crosslinker inclusion in the formed gel for the dosimeters where oxygen was purged during the preparation method. This effect has not been reported in other typical dosimeters and could be attributed to the large differences in the reactivity among these species. PMID- 26275818 TI - Efficiency of barium removal from radioactive waste water using the combination of maghemite and titania nanoparticles in PVA and alginate beads. AB - In this paper, both maghemite (gamma-Fe2O3) and titanium oxide (TiO2) nanoparticles were synthesized and mixed in various ratios and embedded in PVA and alginate beads. Batch sorption experiments were applied for removal of barium ions from aqueous solution under sunlight using the beads. The process has been investigated as a function of pH, contact time, temperature, initial barium ion concentration and TiO2:gamma-Fe2O3 ratios (1:10, 1:60 and 1). The recycling attributes of these beads were also considered. Furthermore, the results revealed that 99% of the Ba(II) was eliminated in 150min at pH 8 under sunlight. Also, the maghemite and titania PVA-alginate beads can be readily isolated from the aqueous solution after the process and reused for at least 7 times without significant losses of their initial properties. The reduction of Ba(II) with maghemite and titania PVA-alginate beads fitted the pseudo first order and second order Langmuir-Hinshelwood (L-H) kinetic model. PMID- 26275819 TI - A systematic review of the predictors of disease progression in patients with autosomal dominant polycystic kidney disease. AB - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterised by progressive renal cyst formation leading to renal failure in the majority of patients. The likelihood and rate of ADPKD progression is difficult to predict and there is a clear need to identify prognostic indicators that could be used to anticipate ADPKD progression, to aid the management of patients in clinical practice. METHODS: A systematic literature review was conducted to identify publications detailing the natural history of ADPKD, including diagnosis, prognosis and progression. Publications were identified and filtered, and data were extracted, based on a predefined research protocol. RESULTS: The review identified 2799 journal articles and 444 conference abstracts; 254 articles, including observational studies, clinical trials and reviews, proceeded to data extraction. Disease progression was associated with a variety of prognostic indicators, most commonly age and total kidney volume (TKV). In the identified clinical trials, the absence of a consistent measure of disease progression led to variation in the primary endpoints used. Consequently, there was difficulty in consistently and effectively demonstrating and comparing the efficacy of investigational treatments across studies. More consistency was found in the observational studies, where disease progression was most frequently measured by TKV and glomerular filtration rate. CONCLUSIONS: This systematic review identified age and TKV as the most commonly cited prognostic indicators in the published ADPKD literature. It is envisaged that this review may inform future research, trial design and predictive models of ADPKD natural history, helping to optimise patient care. PMID- 26275820 TI - Antimalarial drugs for preventing malaria during pregnancy and the risk of low birth weight: a systematic review and meta-analysis of randomized and quasi randomized trials. AB - BACKGROUND: It is known that antimalarial drugs reduce the risk of low birth weight (LBW) in pregnant patients. However, a previous Cochrane review did not evaluate whether the level of antimalarial drug resistance could modify the protective effect of antimalarial drugs in this regard. In addition, no systematic review exists comparing current recommendations for malaria prevention during pregnancy to alternative regimens in Africa. Therefore, we conducted a comprehensive systematic review and meta-analysis to assess the efficacy of antimalarial drugs for malaria prevention during pregnancy in reducing the risk of LBW. METHODS: We searched PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) for articles published up to 21 November 2014, in English or French, and identified additional studies from reference lists. We included randomized and quasi-randomized studies reporting LBW as one of the outcomes. We extracted data and assessed the risk of bias in selected studies. All pooled analyses were based on a random effect model, and we used a funnel plot and trim and fill method to test and adjust for publication bias. RESULTS: A total of 25 studies met the inclusion criteria (37,981 subjects). Compared to no use, all combined antimalarial drugs were associated with a 27% (RR 0.73, 95% CI 0.56-0.97, ten studies) reduction in the risk of LBW. The level of antimalarial drug resistance modified the protective effect of the antimalarial drug used for prevention of LBW during pregnancy. Sulfadoxine-pyrimethamine was not associated with a reduction in the risk of LBW in regions where the prevalence of the dihydropteroate synthase 540E mutation exceeds 50% (RR 0.99, 95% CI 0.80-1.22, three studies). The risk of LBW was similar when sulfadoxine-pyrimethamine was compared to mefloquine (RR 1.05, 95% CI 0.86-1.29, two studies). CONCLUSION: Prophylactic antimalarial drugs and specifically sulfadoxine-pyrimethamine may no longer protect against the risk of LBW in areas of high-level resistance. In Africa, there are currently no suitable alternative drugs to replace sulfadoxine pyrimethamine for malaria prevention during pregnancy. PMID- 26275822 TI - Change of strategy is required for malaria elimination: a case study in Purworejo District, Central Java Province, Indonesia. AB - BACKGROUND: Malaria has been targeted for elimination from Indonesia by 2030, with varying timelines for specific geographical areas based on disease endemicity. The regional deadline for malaria elimination for Java island, given the steady decrease of malaria cases, was the end of 2015. Purworejo District, a malaria-endemic area in Java with an annual parasite incidence (API) of 0.05 per 1,000 population in 2009, aims to enter this elimination stage. This study documents factors that affect incidence and spatial distribution of malaria in Purworejo, such as geomorphology, topography, health system issues, and identifies potential constraints and challenges to achieve the elimination stage, such as inter-districts coordination, decentralization policy and allocation of financial resources for the programme. METHODS: Historical malaria data from 2007 to 2011 were collected through secondary data, in-depth interviews and focus group discussions during study year (2010-2011). Malaria cases were mapped using the village-centroid shape file to visualize its distribution with geomorphologic characteristics overlay and spatial distribution of malaria. API in each village in Purworejo and its surrounding districts from 2007 to 2011 was stratified into high, middle or low case incidence to show the spatiotemporal mapping pattern. RESULTS: The spatiotemporal pattern of malaria cases in Purworejo and the adjacent districts demonstrate repeated concentrated occurrences of malaria in specific areas from 2007 to 2011. District health system issues, i.e., suboptimal coordination between primary care and referral systems, suboptimal inter-district collaboration for malaria surveillance, decentralization policy and the lack of resources, especially district budget allocations for the malaria programme, were major constraints for programme sustainability. CONCLUSIONS: A new malaria elimination approach that fits the local disease transmission, intervention and political system is required. These changes include timely measurements of malaria transmission, revision of the decentralized government system and optimizing the use of the district capitation fund followed by an effective technical implementation of the intervention strategy. PMID- 26275821 TI - Urinary phthalate metabolite concentrations in relation to history of infertility and use of assisted reproductive technology. AB - OBJECTIVE: To examine urinary phthalate metabolite concentrations in pregnant women with planned pregnancies in relation to history of infertility and use of assisted reproductive technology (ART). DESIGN: Phthalate metabolite concentrations were measured in first-trimester urine samples collected from women participating in a prospective pregnancy cohort study. SETTING: Prenatal clinics. PATIENT(S): A total of 750 women, of whom 86 had a history of infertility. Forty-one women used ART to conceive. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Primary outcomes were concentrations of four metabolites of diethylhexyl phthalate (DEHP) and their molar sum (?DEHP). Multivariable analyses compared phthalate metabolite levels in [1] women reporting a history of infertility vs. those who did not (comparison group); and [2] those who used ART to conceive the index pregnancy vs. women with a history of infertility who did not use ART. RESULT(S): Among women with a history of infertility, ?DEHP was significantly lower in women who conceived after ART compared with those who did not (geometric mean ratio: 0.83; 95% confidence interval 0.71-0.98). Similar significant associations were observed for all of the individual DEHP metabolites. There were no differences in DEHP metabolite concentrations between women with a history of infertility and the comparison group. CONCLUSION(S): Women who used ART to conceive had lower first-trimester phthalate metabolite concentrations than women with a history of infertility who did not use ART. Further research is needed to explore whether those pursuing fertility treatments take precautions to avoid exposure to environmental toxins, to improve treatment outcomes. PMID- 26275823 TI - Impact of socioeconomic status and subjective social class on overall and health related quality of life. AB - BACKGROUND: Our objective was to investigate the impact of socioeconomic status and subjective social class on health-related quality of life (HRQOL) vs. overall quality of life (QOL). METHODS: We performed a longitudinal analysis using data regarding 8250 individuals drawn from the Korean Longitudinal Study of Aging (KLoSA). We analyzed differences between HRQOL and QOL in individuals of various socioeconomic strata (high, middle, or low household income and education levels) and subjective social classes (high, middle, or low) at baseline (2009). RESULTS: Individuals with low household incomes and of low subjective social class had the highest probability of reporting discrepant HRQOL and QOL scores (B: 4.796; P < 0.0001), whereas individuals with high household incomes and high subjective social class had the lowest probability of discrepant HRQOL and QOL scores (B: 3.625; P = 0.000). Similar trends were seen when education was used as a proxy for socioeconomic status. CONCLUSION: In conclusion, both household income/subjective social class and education/subjective social class were found to have an impact on the degree of divergence between QOL and HRQOL. Therefore, in designing interventions, socioeconomic inequalities should be taken into account through the use of multi-dimensional measurement tools. PMID- 26275824 TI - Models of buffering of dosage imbalances in protein complexes. AB - BACKGROUND: Stoichiometric imbalances in macromolecular complexes can lead to altered function. Such imbalances stem from under- or over-expression of a subunit of a complex consequent to a deletion, duplication or regulatory mutation of an allele encoding the relevant protein. In some cases, the phenotypic perturbations induced by such alterations can be subtle or be lacking because nonlinearities in the process of protein complex assembly can provide some degree of buffering. RESULTS: We explore with biochemical models of increasing plausibility how buffering can be elicited. Specifically, we analyze the formation of a dimer AB and show that there are particular sets of parameters so that decreasing/increasing the input amount of either A or B translates into a non proportional (buffered) change of AB. The buffer effect also appears in higher-order structures provided that there are intermediate subcomplexes in the assembly process. CONCLUSIONS: We highlight the importance of protein degradation and/or conformational inactivation for buffering to appear. The models sketched here have experimental support but can be further tested with existing biological resources. PMID- 26275825 TI - Expression of calcification and metabolism-related genes in response to elevated pCO2 and temperature in the reef-building coral Acropora millepora. AB - Declining health of scleractinian corals in response to deteriorating environmental conditions is widely acknowledged, however links between physiological and functional genomic responses of corals are less well understood. Here we explore growth and the expression of 20 target genes with putative roles in metabolism and calcification in the branching coral, Acropora millepora, in two separate experiments: 1) elevated pCO2 (464, 822, 1187 and 1638 MUatm) and ambient temperature (27 degrees C), and 2) elevated pCO2 (490 and 822 MUatm) and temperature (28 and 31 degrees C). After 14 days of exposure to elevated pCO2 and ambient temperatures, no evidence of differential expression of either calcification or metabolism genes was detected between control and elevated pCO2 treatments. After 37 days of exposure to control and elevated pCO2, Ubiquinol-Cytochrome-C Reductase Subunit 2 gene (QCR2; a gene involved in complex III of the electron chain transport within the mitochondria and critical for generation of ATP) was significantly down-regulated in the elevated pCO2 treatment in both ambient and elevated temperature treatments. Overall, the general absence of a strong response to elevated pCO2 and temperature by the other 19 targeted calcification and metabolism genes suggests that corals may not be affected by these stressors on longer time scales (37 days). These results also highlight the potential for QCR2 to act as a biomarker of coral genomic responses to changing environments. PMID- 26275826 TI - Separation and purification of hemicellulose-derived saccharides from wood hydrolysate by combined process. AB - Prehydrolysis of wood biomass prior to kraft cooking provides a stream containing hemicellulose-derived saccharides (HDSs) but also undesired non-saccharide compounds (NSCs) that were resulted from lignin depolymerization and carbohydrate degradation. In this study, a combined process consisting of lime treatment, resin adsorption, and gel filtration was developed to separate HDSs from NSCs. The macro-lignin impurities that accounted for 32.2% of NSCs were removed by lime treatment at 1.2% dosage with negligible HDSs loss. The majority of NSCs, lignin derived phenolics, were eliminated by mixed bed ion exchange resin, elevating NSCs removal to 94.0%. The remaining NSCs, furfural and hydroxymethylfurfural, were excluded from HDSs by gel filtration. Chemical composition analysis showed that xylooligosaccharides (XOS) with the degree of depolymerization from 2 to 6 accounted for 28% of the total purified HDSs. PMID- 26275828 TI - Regulation of the neuronal KCNQ2 channel by Src--a dual rearrangement of the cytosolic termini underlies bidirectional regulation of gating. AB - Neuronal M-type K(+) channels are heteromers of KCNQ2 and KCNQ3 subunits, and are found in cell bodies, dendrites and the axon initial segment, regulating the firing properties of neurons. By contrast, presynaptic KCNQ2 homomeric channels directly regulate neurotransmitter release. Previously, we have described a mechanism for gating downregulation of KCNQ2 homomeric channels by calmodulin and syntaxin1A. Here, we describe a new mechanism for regulation of KCNQ2 channel gating that is modulated by Src, a non-receptor tyrosine kinase. In this mechanism, two concurrent distinct structural rearrangements of the cytosolic termini induce two opposing effects: upregulation of the single-channel open probability, mediated by an N-terminal tyrosine, and reduction in functional channels, mediated by a C-terminal tyrosine. In contrast, Src-mediated regulation of KCNQ3 homomeric channels, shown previously to be achieved through the corresponding tyrosine residues, involves the N-terminal-tyrosine-mediated downregulation of the open probability, rather than an upregulation. We argue that the dual bidirectional regulation of KCNQ2 functionality by Src, mediated through two separate sites, means that KCNQ2 can be modified by cellular factors that might specifically interact with either one of the sites, with potential significance in the fine-tuning of neurotransmitters release at nerve terminals. PMID- 26275827 TI - Altering lamina assembly reveals lamina-dependent and -independent functions for A-type lamins. AB - Lamins are intermediate filament proteins that form a fibrous meshwork, called the nuclear lamina, between the inner nuclear membrane and peripheral heterochromatin of metazoan cells. The assembly and incorporation of lamin A/C into the lamina, as well as their various functions, are still not well understood. Here, we employed designed ankyrin repeat proteins (DARPins) as new experimental tools for lamin research. We screened for DARPins that specifically bound to lamin A/C, and interfered with lamin assembly in vitro and with incorporation of lamin A/C into the native lamina in living cells. The selected DARPins inhibited lamin assembly and delocalized A-type lamins to the nucleoplasm without modifying lamin expression levels or the amino acid sequence. Using these lamin binders, we demonstrate the importance of proper integration of lamin A/C into the lamina for nuclear mechanical properties and nuclear envelope integrity. Finally, our study provides evidence for cell-type-specific differences in lamin functions. PMID- 26275829 TI - Overview of digital breast tomosynthesis: Clinical cases, benefits and disadvantages. AB - In France, the national breast cancer-screening program is based on mammography combined with clinical breast examination, and sometimes breast ultrasound for patients with high breast density. Digital breast tomosynthesis is a currently assessed 3D imaging technique in which angular projections of the stationary compressed breast are acquired automatically. When combined with mammography, clinicians can review both conventional (2D) as well as three-dimensional (3D) data. The purpose of this article is to review recent reports on this new breast imaging technique and complements this information with our personal experience. The main advantages of tomosynthesis are that it facilitates the detection and characterization of breast lesions, as well as the diagnosis of occult lesions in dense breasts. However, to do this, patients are exposed to higher levels of radiation than with 2D mammography. In France, the indications for tomosynthesis and its use in breast cancer-screening (individual and organized) are yet to be defined, as is its role in the diagnosis and staging of breast cancer (multiple lesions). Further studies assessing in particular the combined reconstruction of the 2D view using 3D tomosynthesis data acquired during a single breast compression event, and therefore reducing patient exposure to radiation, are expected to provide valuable insight. PMID- 26275830 TI - Correlates between ear postures and emotional reactivity in a wild type mouse species. AB - Facial expressions have been extensively used to assess emotions in humans and thus could be extended to other species that also display facial movements. In mice both painful and fearful situations have been associated with particular shifts in facial expressions. Like other species, mice frequently show a great inter-individual variability when exposed to emotional situations, but so far no study has been conducted to investigate if facial expressions are related to these differences. The aim of this study is to explore if mice of wild origin (Mus spicilegus) express different facial expressions when confronted to novelty and to relate these mimics to their emotional reactivity profile. We used individual exploration scores in a novel odour test and in the elevated plus maze test as proxy measures of individual emotional reactivity. Our results showed that exploration scores in both tests were positively correlated, and both were related to the ear postures expressed by the individuals during their first exploration of the novel odour. This single component of facial expression was in fact a good indicator of inter-individual differences expressed in these two different tests suggesting a strong link between this marker and the individual emotional reactivity. These results highlight the great potential of facial expressions to assess emotional states in animals. PMID- 26275831 TI - Insights into the roles of carrier microstructure in adhesive/carrier-based dry powder inhalation mixtures: Carrier porosity and fine particle content. AB - To gain insights into complex interactions in carrier-based dry powder inhalation mixtures, we studied the relationships between the carrier microstructural characteristics and performance. We used mercury intrusion porosimetry to measure the microstructural characteristics and to also derive the air permeability of eight carriers. We evaluated the performances of inhalation mixtures of each of these carriers and fluticasone propionate after aerosolization from an Aerolizer(r). We did not observe a simple relationship between the carrier total porosity and the performance. Classification of the porosity according to pore size, however, provided interesting insights. The carrier nanoporosity, which refers to pores smaller than micronized drug particles, has a positive influence on the performance. Nanopores reduce the carrier effective contact area and the magnitude of interparticulate adhesion forces in inhalation mixtures. The carrier microporosity, which refers to pores similar in size to drug particles, also has a positive influence on the performance. During mixing, micropores increase the effectiveness of frictional and press-on forces, which are responsible for breaking up of cohesive drug agglomerates and for distribution of drug particles over the carrier surface. On the other hand, the carrier macroporosity, which refers to pores larger than drug particles, apparently has a negative influence on the performance. This influence is likely mediated via the effects of macropores on the powder bed tensile strength and fluidization behavior. The air permeability better represents these effects. The inhalation mixture performance improved as the carrier air permeability decreased. Interestingly, as the carrier fine particle content increased, the carrier microporosity increased and the carrier air permeability decreased. This proposes a new mechanism for the positive effect of fine excipient materials on the performance of carrier-based inhalation mixtures. Fine excipient materials apparently adhere to the surface of coarse carrier particles creating projections and micropores, which increase the effectiveness of mixing. The data also support the mechanism of powder fluidization enforcement by fine excipient materials. The current study clearly demonstrates that the microporosity and the air permeability are key dry powder inhalation carrier performance determinants. Mercury intrusion porosimetry is a useful tool in the dry powder inhalation field; it successfully allowed resolution of carrier pores which contribute differently to the performance. PMID- 26275832 TI - Colorectal tissue engineering: A comparative study between porcine small intestinal submucosa (SIS) and chitosan hydrogel patches. AB - OBJECTIVE: Tissue engineering may provide new operative tools for colorectal surgery in elective indications. The aim of this study was to define a suitable bioscaffold for colorectal tissue engineering. METHODS: We compared 2 bioscaffolds with in vitro and in vivo experiments: porcine small intestinal submucosa (SIS) versus chitosan hydrogel matrix. We assessed nontoxicity of the scaffold in vitro by using human adipose-derived stem cells (hADSC). In vivo, a 1 * 2-cm colonic wall defect was created in 16 rabbits. Animals were divided randomly into 2 groups according to the graft used, SIS or chitosan hydrogel. Graft area was explanted at 4 and 8 weeks. The end points of in vivo experiments were technical feasibility, behavior of the scaffold, in situ putative inflammatory effect, and the quality of tissue regeneration, in particular smooth muscle layer regeneration. RESULTS: In vitro, hADSC attachment and proliferation occurred on both scaffolds without a substantial difference. After proliferation, hADSCs kept their mesenchymal stem cell characteristics. In vivo, one animal died in each group. Eight weeks after implantation, the chitosan scaffold allowed better wound healing compared with the SIS scaffold, with more effective control of inflammatory activity and an integral regeneration of the colonic wall including the smooth muscle cell layer. CONCLUSION: The outcomes of in vitro experiments did not differ greatly between the 2 groups. Macroscopic and histologic findings, however, revealed better wound healing of the colonic wall in the chitosan group suggesting that the chitosan hydrogel could serve as a better scaffold for colorectal tissue engineering. PMID- 26275833 TI - Silencing of plasminogen activator inhibitor-1 suppresses colorectal cancer progression and liver metastasis. AB - BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is reported to be expressed in many cancer cell types and regarded as one of the most informative biochemical markers for poor prognosis. However, no previous study has evaluated whether PAI 1 could serve as a target in antitumor and antimetastasis therapies of colorectal cancer (CRC). METHODS: The plasma level of PAI-1 in CRC patients was detected and its correlation with the clinicopathologic features was evaluated. PAI-1 protein expression was assessed by Western blot assay and immunohistochemistry. The biologic consequences of PAI-1 silencing in colon cancer cell lines and CRC bearing nude mice were also investigated. RESULTS: Plasma PAI-1 level was higher in CRC patients with liver metastasis and correlated with liver metastasis, tumor size, differentiation, serosa infiltration, Duke's stage, and lymphatic metastasis. PAI-1 protein expression in the CRC tissue of patients with liver metastasis was significantly greater than that in those without liver metastasis. In addition, the abilities of proliferation, invasion, and migration of CRC cells transfected with lentivirus expressing PAI-1 small interfering RNA were reduced significantly. Nude mice inoculated with PAI-1 knockdown cells also had fewer metastatic nodules in the liver and smaller tumor volumes. CONCLUSION: Plasma PAI 1 level was increased in CRC patients with liver metastasis, and PAI-1 silencing may significantly compromise the malignant behaviors of CRC cells in vitro and in vivo. These findings may provide evidence for PAI-1 targeted therapy of CRC. PMID- 26275834 TI - Adapted to change: The rapid development of symbiosis in newly settled, fast maturing chemosymbiotic mussels in the deep sea. AB - Symbioses between microbiota and marine metazoa occur globally at chemosynthetic habitats facing imminent threat from anthropogenic disturbance, yet little is known concerning the role of symbiosis during early development in chemosymbiotic metazoans: a critical period in any benthic species' lifecycle. The emerging symbiosis of Idas (sensu lato) simpsoni mussels undergoing development is assessed over a post-larval-to-adult size spectrum using histology and fluorescence in situ hybridisation (FISH). Post-larval development shows similarities to that of both heterotrophic and chemosymbiotic mussels. Data from newly settled specimens confirm aposymbiotic, planktotrophic larval development. Sulphur-oxidising (SOX) symbionts subsequently colonise multiple exposed, non ciliated epithelia shortly after metamorphosis, but only become abundant on gills as these expand with greater host size. This wide-spread bathymodiolin recorded from sulphidic wood, bone and cold-seep habitats, displays a suite of adaptive traits that could buffer against anthropogenic disturbance. PMID- 26275837 TI - Zinc oxide nanoparticle and bovine serum albumin interaction and nanoparticles influence on cytotoxicity in vitro. AB - Bovine serum albumin (BSA) and zinc oxide nanoparticles (ZnO NPs) are chosen as a model system to investigate NPs-protein corona complex formation. ZnO NPs with average size of ~ 20 nm are coated with BSA using covalent and non-covalent conjugation at temperatures of 4 degrees C and 20 degrees C. The interaction mechanism between ZnO NPs and BSA is studied by using UV-vis absorption, fluorescence, synchronous fluorescence and Raman spectroscopy. Raman spectra of BSA in the presence of ZnO NPs are registered for the first time and confirm decreased alpha-helix content, increased unstructured folding and beta-sheet content in BSA structure. The synchronous fluorescence spectra revealed that the hydrophobicity of the tyrosine residue is decreased and that of the tryptophan is increased. The relation of elucidated changes in BSA structure of BSA-coated ZnO NPs cytotoxicity is tested for CHO cell viability and reactive oxygen species (ROS) generation in vitro. Covalent and non-covalent binding of BSA to ZnO NPs reduces ZnO NPs cytotoxicity and ROS generation, however changes in BSA conformation makes corona less protective against ZnO NPs. PMID- 26275838 TI - Directed osteogenic differentiation of mesenchymal stem cell in three-dimensional biodegradable methylcellulose-based scaffolds. AB - Development of three-dimensional (3D) biodegradable scaffolds that can accelerate mesenchymal stem cell (MSC) osteogenic differentiation is a decisive prerequisite for treatment of damaged skeletal tissue. We report herein the preparation of methylcellulose-based (MC) scaffolds using carbonyldiimidazole as cross-linking agent to produce substrates with specific cross-linking density and porous structure, as well as their applications for directing hMSC toward osteoblasts. The mechanical properties of the scaffolds were controlled by cross-linking density. Human MSCs (hMSCs) seeded on the MC scaffolds have penetrated into the pores, and showed high viability (>80%) as revealed by WST assay and Live/Dead assay. Moreover, the results of differentiation experiments indicated that hMSCs cultured on MC substrates displayed high level of osteogenic differentiation marker expression, alkaline phosphatase activity and osteocalcin secretion, suggesting that the MC scaffolds can direct hMSC differentiation toward osteoblasts without inducer treatment and cross-linking density of MC scaffolds have stimulatory effect on inducing differentiation. The 3D MC scaffolds could be applicable as promising scaffolds for bone tissue repair. PMID- 26275835 TI - Geometric and featural systems, separable and combined: Evidence from reorientation in people with Williams syndrome. AB - Spatial reorientation by humans and other animals engages geometric representations of surface layouts as well as featural landmarks; however, the two types of information are thought to be behaviorally and neurally separable. In this paper, we examine the use of these two types of information during reorientation among children and adults with Williams syndrome (WS), a genetic disorder accompanied by abnormalities in brain regions that support use of both geometry and landmarks. Previous studies of reorientation in adolescents and adults with WS have shown deficits in the ability to use geometry for reorientation, but intact ability to use features, suggesting that the two systems can be differentially impaired by genetic disorder. Using a slightly modified layout, we found that many WS participants could use geometry, and most could use features along with geometry. However, the developmental trajectories for the two systems were quite different from one other, and different from those found in typical development. Purely geometric responding was not correlated with age in WS, and search processes appeared similar to those in typically developing (TD) children. In contrast, use of features in combination with geometry was correlated with age in WS, and search processes were distinctly different from TD children. The results support the view that use of geometry and features stem from different underlying mechanisms, that the developmental trajectories and operation of each are altered in WS, and that combination of information from the two systems is atypical. Given brain abnormalities in regions supporting the two kinds of information, our findings suggest that the co-operation of the two systems is functionally altered in this genetic syndrome. PMID- 26275839 TI - Molecular-level insights of early-stage prion protein aggregation on mica and gold surface determined by AFM imaging and molecular simulation. AB - By in situ time-lapse AFM, we investigated early-stage aggregates of PrP formed at low concentration (100 ng/mL) on mica and Au(111) surfaces in acetate buffer (pH 4.5). Remarkably different PrP assemblies were observed. Oligomeric structures of PrP aggregates were observed on mica surface, which was in sharp contrast to the multi-layer PrP aggregates yielding parallel linear patterns observed Au(111) surface. Combining molecular dynamics and docking simulations, PrP monomers, dimers and trimers were revealed as the basic units of the observed aggregates. Besides, the mechanisms of the observed PrP aggregations and the corresponding molecular-substrate and intermolecular interactions were suggested. These interactions involved gold-sulfur interaction, electrostatic interaction, hydrophobic interaction, and hydrogen binding interaction. In contrast, the PrP aggregates observed in pH 7.2 PBS buffer demonstrated similar large ball-like structures on both mica and Au(111) surfaces. The results indicate that the pH of a solution and the surface of the system can have strong effects on supramolecular assemblies of prion proteins. This study provides in-depth understanding on the structural and mechanistic nature of PrP aggregation, and can be used to study the aggregation mechanisms of other proteins with similar misfolding properties. PMID- 26275836 TI - In the name of God: How children and adults judge agents who act for religious versus secular reasons. AB - Many people are guided by religious beliefs, but judgments of religiously and secularly motivated individuals remain unclear. We investigated reasoning about religiously versus secularly motivated characters among 5- to 10-year-olds and adults. In Study 1, theist and non-theist children reported similar attitudes toward theists; however, large differences emerged between theist and non-theist adults. Study 2 obtained similar results using a continuous, rather than forced choice, measure of preference. Additionally, Studies 2-3 tested two explanations for the stronger influence of religious background on adults' versus children's responses. Study 2 did not find strong evidence for the theistic majority account, which posits that the greater perceived prevalence of theists as compared with non-theists influenced children's responses more than adults' responses. The results of Study 3 were consistent with the intuition account, which argues that non-theist adults had effortfully overridden the teleological intuitions that may have influenced children's responses in Studies 1-2 and potentially led children to prefer characters whose beliefs were in line with children's own intuitions. The degree to which teleological intuitions persisted implicitly among adults predicted those adults' pro-theist preferences. These findings offer connections between religious judgments and other areas of social cognition, such as social preferences and teleology. PMID- 26275840 TI - Oral administration of pH-sensitive curcumin-loaded microparticles for ulcerative colitis therapy. AB - Oral colon-specific drug delivery is of great interest for ulcerative colitis (UC) therapy. Here, an emulsion-solvent evaporation method was used to fabricate microparticles (MPs) with pH-sensitive Eudragit S100 (ERS100) and poly(lactide-co glycolide) (PLGA), and the MPs were loaded with curcumin (an efficient anti inflammatory agent). The resultant spherical MPs had a desirable particle size ranging from 1.52 to 1.91 MUm. Their loading efficiency could be regulated by changing the weight ratios of ERS100 and PLGA, with some MPs exhibiting loading efficiencies over 80%. It was observed that the fast release of curcumin from MPs in buffers (pH 1.2 and 6.8) could be significantly decreased by increasing the PLGA content. ERS100/PLGA MPs with a weight ratio of 1:2 (MPs-4) were able to maintain sustained release of curcumin, releasing ~ 48% of the initial drug load at pH 7.2-7.4 during a 20 h-incubation. Most importantly, in vivo experiments revealed that orally administered MPs-4 had a superior therapeutic efficiency in alleviating colitis in a UC mouse model, compared to curcumin. Collectively, our one-step-fabricated curcumin-loaded MPs have the properties of pH-sensitivity, controlled drug release and colon targeting, and thus, may hold promise as a readily scalable drug carrier for the efficient clinical treatment of UC. PMID- 26275842 TI - Normative misperceptions of tobacco use among university students in seven European countries: baseline findings of the 'Social Norms Intervention for the prevention of Polydrug usE' study. AB - INTRODUCTION: Research conducted in North America suggests that students tend to overestimate tobacco use among their peers. This perceived norm may impact personal tobacco use. It remains unclear how these perceptions influence tobacco use among European students. The two aims were to investigate possible self-other discrepancies regarding personal use and attitudes towards use and to evaluate if perceptions of peer use and peer approval of use are associated with personal use and approval of tobacco use. METHODS: The EU-funded 'Social Norms Intervention for the prevention of Polydrug usE' study was conducted in Belgium, Denmark, Germany, Slovak Republic, Spain, Turkey and United Kingdom. In total, 4482 students (71% female) answered an online survey including questions on personal and perceived tobacco use and personal and perceived attitudes towards tobacco use. RESULTS: Across all countries, the majority of students perceived tobacco use of their peers to be higher than their own use. The perception that the majority (>50%) of peers used tobacco regularly in the past two months was significantly associated with higher odds for personal regular use (OR: 2.66, 95% CI: 1.90-3.73). The perception that the majority of peers approve of tobacco use was significantly associated with higher odds for personal approval of tobacco use (OR: 6.49, 95% CI: 4.54-9.28). CONCLUSIONS: Perceived norms are an important predictor of personal tobacco use and attitudes towards use. Interventions addressing perceived norms may be a viable method to change attitudes and tobacco use among European students, and may be a component of future tobacco control policy. PMID- 26275843 TI - Playing Tetris decreases drug and other cravings in real world settings. AB - Most research on cognitive processes in craving has been carried out in the laboratory and focuses on food craving. This study extends laboratory findings to real world settings and cravings for drugs or activities as well as food. Previous laboratory research has found that playing Tetris reduces craving strength. The present study used an ecological momentary assessment protocol in which 31 undergraduate participants carried iPods for a week and were prompted 7 times each day, by SMS message, to use their iPod to report craving. Participants reported craving target and strength (0-100), whether they indulged their previous craving (yes/no), and whether they were under the influence of alcohol (yes/no). Those randomly assigned to the intervention condition (n=15) then played Tetris for 3min and reported their craving again. Those in the monitoring only control condition (n=16) provided baseline craving data to test if Tetris reduced the incidence and strength of spontaneous cravings across the week. Playing Tetris decreased craving strength for drugs (alcohol, nicotine, caffeine), food and drink, and activities (sex, exercise, gaming), with a mean reduction of 13.9 percentage points, effect size f(2)=0.11. This effect was consistent across the week. This is the first demonstration that visual cognitive interference can be used in the field to reduce cravings for substances and activities other than eating. PMID- 26275841 TI - State of the science of health literacy measures: Validity implications for minority populations. AB - OBJECTIVES: To review the evidence supporting the validity of health literacy (HL) measures for ethnic minority populations. METHODS: PubMed, CINAHL, and PsycINFO databases were searched for HL measures between 1965 and 2013. RESULTS: A total of 109HL measures were identified; 37 were non-English HL measures and 72 were English language measures. Of the 72 English language measures, 17 did not specify the racial/ethnic characteristic of their sample. Of the remaining 55 measures, 10 (18%) did not include blacks, 30 (55%) did not include Hispanics, and 35 (64%) did not include Asians in their validation sample. When Hispanic and Asian Americans were included, they accounted for small percentages in the overall sample. Between 2005-2013, a growing number of REALM and TOFHLA translations were identified, and new HL measures for specific cultural/linguistic groups within and outside the United States were developed. CONCLUSIONS: While there are a growing number of new and translated HL measures for minority populations, many existing HL measures have not been properly validated for minority groups. PRACTICE IMPLICATIONS: HL measures that have not been properly validated for a given population should be piloted before wider use. In addition, improving HL instrument development/validation methods are imperative to increase the validity of these measures for minority populations. PMID- 26275844 TI - Association between protective behavioral strategies and problem drinking among college students in the Republic of Korea. AB - OBJECTIVE: The literature indicates that protective behavioral strategies (PBS) have been effective in addressing problem drinking among college students. However, the effects of PBS on problem drinking have not been thoroughly investigated among Korean college students. Thus, the two study aims were to (a) examine drinking behavior among Korean college students and (b) investigate the effects of PBS on problem drinking. METHODS: A pilot study was first conducted to obtain information needed to determine a sample size and to examine the understandability and reliability of seven instruments. The instruments were then used to collect data from full-time college students (N=479). The data were analyzed using (a) descriptive statistics such as frequencies and means for the first aim and (b) multivariate logistic regression for the second aim. RESULTS: Approximately 93% of the respondents had drunk alcohol during the month before the survey, and 72.7% were problem drinkers. The use of PBS significantly decreased the odds of problem drinking (odds ratio [OR]=0.90 [95% CI, 0.87 0.93]). In addition, male gender and positive alcohol expectancy were associated with increased odds of problem drinking (ORs=3.32 [95% CI, 1.59-6.94] and 1.04 [95% CI, 1.01-1.08]), whereas greater age of drinking onset was associated with decreased odds of problem drinking (OR=0.81 [95% CI, 0.70-0.94]). CONCLUSIONS: Given the prevalence of the drinking problem among Korean college students, it is important to develop and implement interventions that will encourage students to use PBS in order to avoid problem drinking and its negative consequences. PMID- 26275845 TI - Estimating the risk of Middle East respiratory syndrome (MERS) death during the course of the outbreak in the Republic of Korea, 2015. AB - OBJECTIVES: A large cluster of the Middle East respiratory syndrome (MERS) linked to healthcare setting occurred from May to July 2015 in the Republic of Korea. The present study aimed to estimate the case fatality ratio (CFR) by appropriately taking into account the time delay from illness onset to death. We then compare our estimate against previously published values of the CFR for MERS, i.e., 20% and 40%. METHODS: Dates of illness onset and death of the MERS outbreak in the Republic of Korea were extracted from secondary data sources. Using the known distribution of time from illness onset to death and an integral equation model, we estimated the delay-adjusted risk of MERS death for the South Korean cluster. RESULTS: Our most up-to-date estimate of CFR for the MERS outbreak in South Korea was estimated at 20.0% (95% confidence intervals (CI): 14.6, 26.2). During the course of the outbreak, estimate of the CFR in real time appeared to have decreased and become significantly lower than 40%. CONCLUSIONS: The risk of MERS death in Korea was consistent with published CFR. The estimate decreased with time perhaps due to time-dependent increase in case ascertainment. Crude ratio of cumulative deaths to cases underestimates the actual risk of MERS death because of time delay from illness onset to death. PMID- 26275846 TI - Improving imaging to optimize screening strategies for carotid artery stenosis. AB - Carotid stenosis is a major risk factor for ischemic stroke. Recently, the United States Preventive Services Task Force issued a recommendation against screening for carotid stenosis in the general population. There is the potential for efficient risk-stratifying or staged screening approaches that identify individuals at highest risk for carotid stenosis and stroke, but these tools have yet to be proven effective in external validation studies. In this paper, we review how medical imaging can be used to detect carotid stenosis and highlight several areas that could be improved to identify potentially efficient screening strategies for carotid stenosis. PMID- 26275847 TI - The radiological findings of chordoid glioma: report of two cases, one case with MR spectroscopy. AB - Chordoid glioma is a rare tumor that often originate from the third ventricle. We reported two cases of choroid glioma. Although calcification is a rare findings, dot-like calcification was present on one case. On contrast images, one case demonstrated strong, homogeneous enhancement. On MR spectroscopy (MRS) images, the tumor showed high choline (Cho), low N-acetyl aspartate (NAA) and Cho/Cr=2.38, NAA/Cr=1.19, NAA/Cr=1.19. This might mimic a low-grade tumour. MRS offers additional information and facilitate differential diagnosis for chordoid glioma. PMID- 26275848 TI - IRSp53/BAIAP2 in dendritic spine development, NMDA receptor regulation, and psychiatric disorders. AB - IRSp53 (also known as BAIAP2) is a multi-domain scaffolding and adaptor protein that has been implicated in the regulation of membrane and actin dynamics at subcellular structures, including filopodia and lamellipodia. Accumulating evidence indicates that IRSp53 is an abundant component of the postsynaptic density at excitatory synapses and an important regulator of actin-rich dendritic spines. In addition, IRSp53 has been implicated in diverse psychiatric disorders, including autism spectrum disorders, schizophrenia, and attention deficit/hyperactivity disorder. Mice lacking IRSp53 display enhanced NMDA (N methyl-d-aspartate) receptor function accompanied by social and cognitive deficits, which are reversed by pharmacological suppression of NMDA receptor function. These results suggest the hypothesis that defective actin/membrane modulation in IRSp53-deficient dendritic spines may lead to social and cognitive deficits through NMDA receptor dysfunction. This article is part of the Special Issue entitled 'Synaptopathy--from Biology to Therapy'. PMID- 26275850 TI - The shifting sands of medico-legal intra-partum Ctg (I-P Ctg) monitoring. AB - Intra-partum (IP) surveillance of the unborn child by cardiotacography (CTG) monitoring is the commonest obstetric procedure in the developed world.(1) It is also the most medico-legally contested obstetric procedure in labour. In 2011, 'birth asphyxia' comprised 50% of the UK National Health Service (NHS) litigation costs,(2) and in the 2000-2010 decade, the same NHS paid out L3.1 billion for maternity medico-legal claims (the highest of any speciality), mostly involving cerebral palsy and CTG misinterpretation.(3) This article looks at a number of characteristics of IP CTG monitoring which argue for its questionable solidity of base in court proceedings. PMID- 26275851 TI - The Medical Practitioners Tribunal Service: Modernising fitness to practise adjudication. PMID- 26275852 TI - Genetic variability of porcine circovirus 2 (PCV2) field isolates from vaccinated and non-vaccinated pig herds in Germany. AB - Porcine circovirus 2 (PCV2) is responsible for a wide range of associated diseases (PCVD) affecting swine production worldwide. Highly efficient commercial vaccines induce protective immunity, but PCV2 is still circulating in vaccinated farms. Thus, and because of the virus high mutation rate, recent findings provide concerns about PCV2 strains capable to escape vaccination. Based on 2156 samples from individual pigs of 315 herds from Germany we describe a high effectivity of vaccination between 2008 and the third quarter of 2011. In this period, virus load dropped continuously and at the end of this period it hardly reached the limit of quantification. Thereafter, virus loads re-increased, although most of the herds were still vaccinated. Sixty-two randomly selected samples from vaccinated (n=28) and non-vaccinated (n=26) herds between 2008 and 2012 were completely sequenced. As compared to the PCV2b reference sequence 259 polymorphisms were detected. Polymorhisms were analysed for associations to vaccination status, genotype (PCV2a/PCV2b), and virus load. PCV2a sequences were significantly repelled by PCV2b. One SNP at position 1182 (g.1182G>T), involved in capsid epitope formation, was significantly associated with the PCV2 genotype (2a/2b). Moreover, this SNP was affected by vaccination, with effects on allele frequencies and viral load, independent from the PCV2 genotype (2a/2b). We conclude that there is indeed evidence for a selectional impact of vaccination on the PCV2 sequence, especially on nucleotides involved in epitope formation. Such variation might be responsible for the observed re-increase of PCV2-loads in samples from the end of 2011 in Germany. PMID- 26275849 TI - Histamine and the striatum. AB - The neuromodulator histamine is released throughout the brain during periods of wakefulness. Combined with an abundant expression of histamine receptors, this suggests potential widespread histaminergic control of neural circuit activity. However, the effect of histamine on many of these circuits is unknown. In this review we will discuss recent evidence for histaminergic modulation of the basal ganglia circuitry, and specifically its main input nucleus; the striatum. Furthermore, we will discuss recent findings of histaminergic dysfunction in several basal ganglia disorders, including in Parkinson's disease and most prominently, in Tourette's syndrome, which has led to a resurgence of interest in this neuromodulator. Combined, these recent observations not only suggest a central role for histamine in modulating basal ganglia activity and behaviour, but also as a possible target in treating basal ganglia disorders. This article is part of the Special Issue entitled 'Histamine Receptors'. PMID- 26275853 TI - Zoonotic risks from small ruminants. AB - Zoonoses are infections that spread naturally between species (sometimes by a vector) from animals to other animal species or to humans or from humans to animals. Most of the zoonoses diagnosed in sheep and goats are transmitted by close contact of man with these animals and are, more often, occupational diseases that principally affect breeders, veterinarians and/or slaughterhouse workers. Some other diseases have an airborne transmission and affect the population in the vicinity of sheep/goat farms. Due to the fact that small ruminants are almost the only remaining animals which are migrating in industrialised countries, there is a severe risk for transmitting the diseases. Some other zoonotic diseases are foodborne diseases, which are mainly transmitted from animals to humans and to other animal species by contaminated food and water. Within the last decade central Europe was threatened by some new infections, e.g., bluetongue disease and schmallenberg disease, which although not of zoonotic interest, are caused by pathogens transmitted by vectors. Causal agents of both diseases have found highly effective indigenous vectors. In the future, climate change may possibly modify conditions for the vectors and influence their distribution and competence. By this, other vector-borne zoonotic infections may propagate into former disease free countries. Changes in human behaviour in consummation and processing of food, in animal housing and management may also influence future risks for zoonosis. Monitoring, prevention and control measures are proposed to limit further epidemics and to enable the containment of outbreaks. Measures depend mainly on the damage evoked or anticipated by the disease, the local situation, and the epidemiology of the zoonoses, the presence of the infective agent in wild and other animals, as well as the resistance of the causal microorganisms in the environment and the possibility to breed sheep and goats which are resistant to specific infections. In this review, the clinical signs in animals and humans of the main sheep and goat zoonoses, as well as the transmission route and the control measures are reported. Brucellosis, chlamydophilosis, Q fever, Orf, Rift valley fever and Bovine Spongiform Encephalopathy are described in greater detail, in order to determine factors that contribute to the choice of the control strategies. PMID- 26275854 TI - Diagnostic pathology in microbial diseases of sheep or goats. AB - Post-mortem examination is a key step in the diagnostic process of infectious diseases in sheep and goats. Diagnostic pathology deals with identification and study of lesions, at the same time providing also significant clues regarding pathogenesis of the diseases. This article reviews the salient pathological findings associated with the most significant infectious diseases of sheep and goats present in countries where small ruminants are a relevant agricultural industry. Lesions are reviewed according to the different organ systems where they occur. Emphasis has been given in the description of the salient lesional patterns than can be identified in each organ and which can be of help in the differential diagnosis of the lesions caused by bacteria, viruses, fungi or prions. Finally, a review of the usefulness of ancillary tests that may be used on various tissue samples for performing an aetiological diagnosis, is included; the application of various techniques, from immunohistochemistry to molecular biology-based tests, is described. PMID- 26275855 TI - Fusion to a highly stable consensus albumin binding domain allows for tunable pharmacokinetics. AB - A number of classes of proteins have been engineered for high stability using consensus sequence design methods. Here we describe the engineering of a novel albumin binding domain (ABD) three-helix bundle protein. The resulting engineered ABD molecule, called ABDCon, is expressed at high levels in the soluble fraction of Escherichia coli and is highly stable, with a melting temperature of 81.5 degrees C. ABDCon binds human, monkey and mouse serum albumins with affinity as high as 61 pM. The solution structure of ABDCon is consistent with the three helix bundle design and epitope mapping studies enabled a precise definition of the albumin binding interface. Fusion of a 10 kDa scaffold protein to ABDCon results in a long terminal half-life of 60 h in mice and 182 h in cynomolgus monkeys. To explore the link between albumin affinity and in vivo exposure, mutations were designed at the albumin binding interface of ABDCon yielding variants that span an 11 000-fold range in affinity. The PK properties of five such variants were determined in mice in order to demonstrate the tunable nature of serum half-life, exposure and clearance with variations in albumin binding affinity. PMID- 26275856 TI - Assessing the prediction fidelity of ancestral reconstruction by a library approach. AB - Ancestral reconstruction is a powerful tool for studying protein evolution as well as for protein design and engineering. However, in many positions alternative predictions with relatively high marginal probabilities exist, and thus the prediction comprises an ensemble of near-ancestor sequences that relate to the historical ancestor. The ancestral phenotype should therefore be explored for the entire ensemble, rather than for the sequence comprising the most probable amino acid at all positions [the most probable ancestor (mpa)]. To this end, we constructed libraries that sample ensembles of near-ancestor sequences. Specifically, we identified positions where alternatively predicted amino acids are likely to affect the ancestor's structure and/or function. Using the serum paraoxonases (PONs) enzyme family as a test case, we constructed libraries that combinatorially sample these alternatives. We next characterized these libraries, reflecting the vertebrate and mammalian PON ancestors. We found that the mpa of vertebrate PONs represented only one out of many different enzymatic phenotypes displayed by its ensemble. The mammalian ancestral library, however, exhibited a homogeneous phenotype that was well represented by the mpa. Our library design strategy that samples near-ancestor ensembles at potentially critical positions therefore provides a systematic way of examining the robustness of inferred ancestral phenotypes. PMID- 26275857 TI - Regulating the surface poly(ethylene glycol) density of polymeric nanoparticles and evaluating its role in drug delivery in vivo. AB - Poly(ethylene glycol) (PEG) is usually used to protect nanoparticles from rapid clearance in blood. The effects are highly dependent on the surface PEG density of nanoparticles. However, there lacks a detailed and informative study in PEG density and in vivo drug delivery due to the critical techniques to precisely control the surface PEG density when maintaining other nano-properties. Here, we regulated the polymeric nanoparticles' size and surface PEG density by incorporating poly(epsilon-caprolactone) (PCL) homopolymer into poly(ethylene glycol)-block-poly(epsilon-caprolactone) (PEG-PCL) and adjusting the mass ratio of PCL to PEG-PCL during the nanoparticles preparation. We further developed a library of polymeric nanoparticles with different but controllable sizes and surface PEG densities by changing the molecular weight of the PCL block in PEG PCL and tuning the molar ratio of repeating units of PCL (CL) to that of PEG (EG). We thus obtained a group of nanoparticles with variable surface PEG densities but with other nano-properties identical, and investigated the effects of surface PEG densities on the biological behaviors of nanoparticles in mice. We found that, high surface PEG density made the nanoparticles resistant to absorption of serum protein and uptake by macrophages, leading to a greater accumulation of nanoparticles in tumor tissue, which recuperated the defects of decreased internalization by tumor cells, resulting in superior antitumor efficacy when carrying docetaxel. PMID- 26275858 TI - Pharmaceutical inhibition of glycogen synthetase kinase 3 beta suppresses wear debris-induced osteolysis. AB - Aseptic loosening is associated with the development of wear debris-induced peri implant osteolytic bone disease caused by an increased osteoclastic bone resorption and decreased osteoblastic bone formation. However, no effective measures for the prevention and treatment of peri-implant osteolysis currently exist. The aim of this study was to determine whether lithium chloride (LiCl), a selective inhibitor of glycogen synthetase kinase 3 beta (GSK-3beta), mitigates wear debris-induced osteolysis in a murine calvarial model of osteolysis. GSK 3beta is activated by titanium (Ti) particles, and implantation of Ti particles on the calvarial surface in C57BL/6 mice resulted in osteolysis caused by an increase in the number of osteoclasts and a decrease in the number of osteoblasts. Mice implanted with Ti particles were gavage-fed LiCl (50 or 200 mg kg(-1)d(-1)), 6 days per week for 2 weeks. The LiCl treatment significantly inhibited GSK-3beta activity and increased beta-catenin and axin-2 expression in a dose-dependent manner, dramatically mitigating the Ti particle-induced suppression of osteoblast numbers and the expression of bone formation markers. Finally, we demonstrated that inhibition of GSK-3beta suppresses osteoclast differentiation and reduces the severity of Ti particle-induced osteolysis. The results of this study indicate that Ti particle-induced osteolysis is partly dependent on GSK-3beta and, therefore, the canonical Wnt signaling pathway. This suggests that selective inhibitors of GSK-3beta such as LiCl may help prevent and treat wear debris-induced osteolysis. PMID- 26275859 TI - A novel CX3CR1 antagonist eluting stent reduces stenosis by targeting inflammation. AB - We evaluated the therapeutic efficacy of a novel drug eluting stent (DES) inhibiting inflammation and smooth muscle cell (SMC) proliferation. We identified CX3CR1 as a targetable receptor for prevention of monocyte adhesion and inflammation and in-stent neointimal hyperplasia without interfering with stent re-endothelization. Efficacy of AZ12201182 (AZ1220), a CX3CR1 antagonist was evaluated in inhibition of monocyte attachment in vitro. A prototype AZ1220 eluting PLGA-based polymer coated stent developed with an optimal elution profile and dose of 1 MUM/stent was tested over 4 weeks in a porcine model of coronary artery stenting. Polymer coated stents without AZ1220 and bare metal stents were used as controls. AZ1220 inhibited monocyte attachment to CX3CL1 in a dose dependent manner. AZ1220 eluted from polymer coated stents in an ex vivo flow system retained bioactivity in inhibiting monocyte attachment to CX3CL1. At 4 weeks following deployment, AZ1220 eluting stents significantly reduced (~60%) in stent stenosis compared to both bare metal and polymer only coated stents and markedly reduced peri-stent inflammation and monocyte/macrophage accumulation without affecting re-endothelization. Anti-CX3CR1 drug eluting stents potently inhibited in-stent stenosis and may offer an alternative to mTOR targeting by current DES, specifically inhibiting polymer-induced inflammatory response and SMC proliferation, while retaining an equivalent re-endothelization response to bare metal stents. PMID- 26275861 TI - Extension of a dynamic headspace multi-volatile method to milliliter injection volumes with full sample evaporation: Application to green tea. AB - An extension of multi-volatile method (MVM) technology using the combination of a standard dynamic headspace (DHS) configuration, and a modified DHS configuration incorporating an additional vacuum module, was developed for milliliter injection volume of aqueous sample with full sample evaporation. A prior step involved investigation of water management by weighing of the water residue in the adsorbent trap. The extended MVM for 1 mL aqueous sample consists of five different DHS method parameter sets including choice of the replaceable adsorbent trap. An initial two DHS sampling sets at 25 degrees C with the standard DHS configuration using a carbon-based adsorbent trap target very volatile solutes with high vapor pressure (>10 kPa) and volatile solutes with moderate vapor pressure (1-10 kPa). Subsequent three DHS sampling sets at 80 degrees C with the modified DHS configuration using a Tenax TA trap target solutes with low vapor pressure (<1 kPa) and/or hydrophilic characteristics. After the five sequential DHS samplings using the same HS vial, the five traps are sequentially desorbed with thermal desorption in reverse order of the DHS sampling and the desorbed compounds are trapped and concentrated in a programmed temperature vaporizing (PTV) inlet and subsequently analyzed in a single GC-MS run. Recoveries of 21 test aroma compounds in 1 mL water for each separate DHS sampling and the combined MVM procedure were evaluated as a function of vapor pressure in the range of 0.000088-120 kPa. The MVM procedure provided high recoveries (>88%) for 17 test aroma compounds and moderate recoveries (44-71%) for 4 test compounds. The method showed good linearity (r(2)>0.9913) and high sensitivity (limit of detection: 0.1-0.5 ng mL(-1)) even with MS scan mode. The improved sensitivity of the method was demonstrated with analysis of a wide variety of aroma compounds in brewed green tea. Compared to the original 100 MUL MVM procedure, this extension to 1 mL MVM allowed detection of nearly twice the number of aroma compounds, including 18 potent aroma compounds from top-note to base-note (e.g. 2,3 butanedione, coumarin, furaneol, guaiacol, cis-3-hexenol, linalool, maltol, methional, 3-methyl butanal, 2,3,5-trimethyl pyrazine, and vanillin). Sensitivity for 23 compounds improved by a factor of 3.4-15 under 1 mL MVM conditions. PMID- 26275860 TI - Dragon fruit-like biocage as an iron trapping nanoplatform for high efficiency targeted cancer multimodality imaging. AB - Natural biopolymer based multifunctional nanomaterials are perfect candidates for multimodality imaging and therapeutic applications. Conventional methods of building multimodal imaging probe require either cross-linking manners to increase its in vivo stability or attach a target module to realize targeted imaging. In this study, the intrinsic photoacoustic signals and the native strong chelating properties with metal ions of melanin nanoparticle (MNP), and transferrin receptor 1 (TfR1) targeting ability of apoferritin (APF) was employed to construct an efficient nanoplatform (AMF) without tedious assembling process. Smart APF shell significantly increased metal ions loading (molar ratio of 1:800, APF/Fe(3+)) and therefore improved magnetic resonance imaging (MRI) sensitivity. Moreover, synergistic use of Fe(3+) and APF contributed to high photoacounstic imaging (PAI) sensitivity. AMF showed excellent bio-stability and presented good in vivo multimodality imaging (PET/MRI/PAI) properties (good tumor uptake, high specificity and high tumor contrast) in HT29 tumor because of its targeting property combined with the enhanced permeability and retention (EPR) effect, making it promising in theranostics and translational nanomedicine. PMID- 26275862 TI - Analytical methods in sphingolipidomics: Quantitative and profiling approaches in food analysis. AB - In recent years, sphingolipidomics has emerged as an interesting omic science that encompasses the study of the full sphingolipidome characterization, content, structure and activity in cells, tissues or organisms. Like other omics, it has the potential to impact biomarker discovery, drug development and systems biology knowledge. Concretely, dietary food sphingolipids have gained considerable importance due to their extensively reported bioactivity. Because of the complexity of this lipid family and their diversity among foods, powerful analytical methodologies are needed for their study. The analytical tools developed in the past have been improved with the enormous advances made in recent years in mass spectrometry (MS) and chromatography, which allow the convenient and sensitive identification and quantitation of sphingolipid classes and form the basis of current sphingolipidomics methodologies. In addition, novel hyphenated nuclear magnetic resonance (NMR) strategies, new ionization strategies, and MS imaging are outlined as promising technologies to shape the future of sphingolipid analyses. This review traces the analytical methods of sphingolipidomics in food analysis concerning sample extraction, chromatographic separation, the identification and quantification of sphingolipids by MS and their structural elucidation by NMR. PMID- 26275863 TI - Study of retention and peak shape in hydrophilic interaction chromatography over a wide pH range. AB - Retention factor and column efficiency measurements were made for 14 test compounds comprising acids, bases and neutrals on two pairs of amide and bare silica HILIC columns, each pair obtained from a different manufacturer. The columns were tested with up to 6 different mobile phases with acetonitrile-water containing formic (FA), trifluoroacetic (TFA), heptafluorobutyric acids (HFBA) and ammonium salt buffers at w(w)pH 3, 6 and 9. Measurements of mobile phase pH in water (w(w)pH) and in the aqueous-organic mixture (w(s)pH) were performed, and calculations of ionic strength made, in order to aid interpretation of the chromatographic results. Stronger acids like TFA produced very different selectivity compared with ammonium formate buffers at similar aqueous pH. On a given column using TFA as additive, the retention of strongly acidic solutes was considerably increased relative to that of bases. Some bases even showed exclusion on both amide, and on a hybrid silica column. Conversely, in ammonium formate buffers of similar aqueous pH, bases had increased retention compared with acids, particularly on the bare silica columns. This result can be attributed to the higher pH of the salt buffers when measured in the aqueous organic phase and interaction with negatively charged silanols. It is possible that the silica surface becomes positively charged at the low pH of TFA, leading to anion exchange properties that become competitive with the cation exchange properties normally attributed to silanol dissociation, although other explanations of these results are possible. Very marked selectivity differences were obtained by use of TFA in the mobile phase. Useful selectivity differences may also be obtained with salt buffers at different pH if the use of TFA is not desired due to its relatively unfavourable properties in mass spectrometry. PMID- 26275865 TI - High incidence of metabolic syndrome further increases cardiovascular risk in patients with type 2 diabetes. Implications for everyday practice. PMID- 26275864 TI - Diabetes mellitus and cancer of the digestive organs: An Italian population-based cohort study. AB - AIMS: The association between diabetes mellitus and the occurrence of digestive organs cancers was investigated in the Italian region Friuli Venezia Giulia. The risk of cancer associated with oral antidiabetic drugs among subjects with type 2 diabetes was also assessed. METHODS: This was a retrospective population-based cohort study based on the 2002-2014 regional administrative health data. Incident digestive cancers were identified through the hospital discharge diagnoses. The incidence rates of cancer at different sites were calculated for type 1 and 2 diabetics and for non-diabetics. Proportional hazard models were built to assess the risk of cancer associated with diabetes and antidiabetic drugs. RESULTS: Diabetes was associated with increased risk of digestive cancers. Liver and pancreatic cancers were associated with the highest hazard ratios. Among type 2 diabetics, total number of metformin prescriptions was associated with reduced risk of most types of digestive cancers; sulfonylureas with reduced risk of stomach and pancreatic cancer. CONCLUSIONS: In this Italian population the excess risk of digestive cancers for diabetic patients was confirmed. Further research is needed to clarify the role of antidiabetic drugs. PMID- 26275866 TI - Synthesis, biological evaluation, and docking studies of novel thiourea derivatives of bisindolylmethane as carbonic anhydrase II inhibitor. AB - This article describes discovery of 29 novel bisindolylmethanes consisting of thiourea moiety, which had been synthesized through three steps. These novel bisindolylmethane derivatives evaluated for their potential inhibitory activity against carbonic anhydrase (CA) II. The results for in vitro assay of carbonic anhydrase II inhibition activity showed that some of the compounds are capable of suppressing the activity of carbonic anhydrase II. Bisindoles having halogen at fifth position showed better inhibitory activity as compared to unsubstituted bisindoles. Derivatives showing inhibition activity docked to further, understand the binding behavior of these compounds with carbonic anhydrase II. Docking studies for the active compound 3j showed that nitro substituent at para position fits into the core of the active site. The nitro substituent of compound 3j is capable of interacting with Zn ion. This interaction believed to be the main factor causing inhibition activity to take place. PMID- 26275867 TI - Incidental diagnosis of HLRCC following investigation for Asperger Syndrome: actionable and actioned. AB - Incidental findings are inevitable as clinical research and practice transitions from a single gene approach to a genomic approach. A novel deletion of the Fumarate Hydratase (FH) gene was identified in a 22 year old male who underwent a molecular karyotype as part of an autism spectrum disorder research project. This unexpected result implies a predisposition to Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC), a rare, autosomal dominant condition and has unforeseen implications for him and his family. We review the typical features and management of HLRCC and discuss the challenges that face health professionals, as genetic testing advances and becomes more accessible. PMID- 26275870 TI - Role of Solvent Dynamics in Photoinduced Proton-Coupled Electron Transfer in a Phenol-Amine Complex in Solution. AB - Photoinduced proton-coupled electron transfer (PCET) plays an essential role in a wide range of energy conversion processes. Previous experiments on a phenol-amine complex in solution provided evidence of an electron-proton transfer (EPT) excited state characterized by both intramolecular charge transfer and proton transfer from the phenol to the amine. Herein we analyze hundreds of surface hopping trajectories to investigate the role of solvent dynamics following photoexcitation to the EPT state. This solvent dynamics leads to a significant decrease in the energy gap between the ground and EPT states, thereby facilitating decay to the ground state, and generates an electrostatic environment conducive to proton transfer on the EPT state. In addition to solvent reorganization, the geometrical properties at the hydrogen-bonding interface must be suitable to allow proton transfer. These mechanistic insights elucidate the underlying fundamental physical principles of photoinduced PCET processes. PMID- 26275868 TI - Long-term outcome of sporadic and FAP-associated desmoid tumors treated with high dose selective estrogen receptor modulators and sulindac: a single-center long term observational study in 134 patients. AB - Aim of this study is to evaluate the outcome of long-term conservative treatment with sulindac and high-dose selective estrogen receptor modulators (SERMs) for sporadic and FAP-associated desmoid tumors. Desmoids are very rare tumors in the general population but occur frequently in FAP patients, being encountered in 23 38 %. Treatment of desmoids is still most controversial since response cannot be predicted and they are prone to develop recurrence. This study included all desmoid patients that were treated and followed at our institution and had completed at least 1 year of treatment. Response was defined as stable size or regression of desmoid size between two CT or MRI scans. A total of 134 patients were included. 64 (47.8 %) patients had a confirmed diagnosis of FAP, 69 (51.5 %) patients were sporadic. Overall 114 (85.1 %) patients showed regressive or stable desmoid size. Patients with previous history of multiple desmoid-related surgeries showed less-favorable response. The mean time to reach at least stable size was 14.9 (+/-9.1) months. After regression or stabilization, medication was tapered in 69 (60.5 %) of the treated patients with only one long-term recurrence after >10 years. The results of this study fortify the role of sulindac and high dose SERMs as an effective and safe treatment for both, sporadic and FAP associated desmoid tumors. While invasive treatment frequently results in high recurrence rates, high morbidity and high mortality, this conservative treatment is successful in most patients. The recurrence rate is negligible with no desmoid related mortality in this large series. Therefore surgical resection, especially for mesenteric desmoids, should be deferred favoring this convincingly effective, well tolerated regimen. PMID- 26275869 TI - Psychiatrists' Perceptions of World of Warcraft and Other MMORPGs. AB - Video game use, particularly massively-multiplayer online games (MMOs) and massively-multiplayer online role-playing games (MMORPGs), has been a focus of considerable research in recent years. However, little is known regarding how mental health workers perceive patients and clients who report playing them. The present study examines whether psychiatrists play MMOs/MMORPGs and how they perceive those who play them. Psychiatrists (N = 48) at a tertiary care centre in Canada completed a questionnaire assessing history of playing video games as well as whether they associate such use with psychopathology. Only 36.7 % believed there was an association between psychopathology and MMO/MMORPG use. Implications for clinical practice and future research are discussed. PMID- 26275871 TI - Rapid Adjustment of Circadian Clocks to Simulated Travel to Time Zones across the Globe. AB - Daily rhythms in mammalian physiology and behavior are generated by a central pacemaker located in the hypothalamic suprachiasmatic nuclei (SCN), the timing of which is set by light from the environment. When the ambient light-dark cycle is shifted, as occurs with travel across time zones, the SCN and its output rhythms must reset or re-entrain their phases to match the new schedule-a sluggish process requiring about 1 day per hour shift. Using a global assay of circadian resetting to 6 equidistant time-zone meridians, we document this characteristically slow and distance-dependent resetting of Syrian hamsters under typical laboratory lighting conditions, which mimic summer day lengths. The circadian pacemaker, however, is additionally entrainable with respect to its waveform (i.e., the shape of the 24-h oscillation) allowing for tracking of seasonally varying day lengths. We here demonstrate an unprecedented, light exposure-based acceleration in phase resetting following 2 manipulations of circadian waveform. Adaptation of circadian waveforms to long winter nights (8 h light, 16 h dark) doubled the shift response in the first 3 days after the shift. Moreover, a bifurcated waveform induced by exposure to a novel 24-h light-dark light-dark cycle permitted nearly instant resetting to phase shifts from 4 to 12 h in magnitude, representing a 71% reduction in the mismatch between the activity rhythm and the new photocycle. Thus, a marked enhancement of phase shifting can be induced via nonpharmacological, noninvasive manipulation of the circadian pacemaker waveform in a model species for mammalian circadian rhythmicity. Given the evidence of conserved flexibility in the human pacemaker waveform, these findings raise the promise of flexible resetting applicable to circadian disruption in shift workers, frequent time-zone travelers, and any individual forced to adjust to challenging schedules. PMID- 26275873 TI - Epithelial Cell Death and Inflammation in Skin. AB - The presence of dying cells in inflamed tissues has been recognized since many years, but until recently cell death was considered primarily a consequence of inflammation. Recent data in mouse models suggest that cell death could provide a potent trigger of inflammation. The identification of necroptosis as a new type of regulated necrotic cell death that is induced by death receptors, toll like receptors and type I interferon receptor indicated that necroptosis could contribute to the proinflammatory properties of these receptors. This is particularly relevant to the skin, a tissue that provides a life-sustaining structural and immunological barrier with the environment and is constantly exposed to mechanical, chemical, and microbial insults. Studies in mouse models showed that sensitization of keratinocytes to apoptosis or necroptosis triggered by TNF and other stimuli causes severe chronic inflammatory skin lesions. In addition, keratinocyte death is a prominent histopathological feature of many inflammatory skin diseases, suggesting that death of epithelial cells could contribute to the pathogenesis of skin inflammation . Here we review recent studies in genetic mouse models providing evidence that keratinocyte death is a potent trigger of skin inflammation and discuss their potential relevance for human inflammatory skin diseases. PMID- 26275872 TI - Changes in presepsin concentrations in surgical patients with end-stage kidney disease undergoing living kidney transplantation: a pilot study. AB - Presepsin is a useful marker for differentiating sepsis from non-infection related systemic inflammatory response syndrome. There are data describing elevated presepsin concentrations in patients with kidney dysfunction even in the absence of sepsis, but corresponding data for patients with end-stage kidney disease (ESKD) undergoing living kidney transplantation (LKT) are lacking. We investigated the changes in presepsin concentrations in this patient group in order to elucidate any relationship with renal function. Written informed consent was obtained from patients with ESKD requiring hemodialysis who underwent LKT from June 2014 through March 2015 at Hirosaki University Hospital. Patients with obvious signs of infection were excluded. Perioperative presepsin and procalcitonin concentrations were measured before induction of anesthesia, on admission to the intensive care unit after surgery, and on postoperative day (POD) 1 and POD 2. Preoperative presepsin concentration was markedly higher than the upper limit of normal in patients with ESKD (1252 +/- 451 pg/mL). Presepsin concentrations consistently decreased after LKT. Moreover, presepsin concentration was strongly correlated with serum creatinine (r (2) = 0.72, n = 24, p < 0.001). These data suggest that the kidney clearly plays an important role in the metabolism and excretion of presepsin. PMID- 26275874 TI - Roles of the NF-kappaB Pathway in B-Lymphocyte Biology. AB - NF-kappaB was originally identified as a family of transcription factors that bind the enhancer of the immunoglobulin kappa light-chain gene. Although its function in the regulation of immunoglobulin kappa light-chain gene remains unclear, NF-kappaB plays critical roles in development, survival, and activation of B lymphocytes. In B cells, many receptors, including B-cell antigen receptor (BCR), activate NF-kappaB pathway, and the molecular mechanism of receptor mediated activation of IkappaB kinase (IKK) complex has been partially revealed. In addition to normal B lymphocytes, NF-kappaB is also involved in the growth of some types of B-cell lymphomas, and many oncogenic mutations involved in constitutive activation of the NF-kappaB pathway were recently identified in such cancers. In this review, we first summarize the function of NF-kappaB in B-cell development and activation, and then describe recent progress in understanding the molecular mechanism of receptor-mediated activation of the IKK complex, focusing on the roles of the ubiquitin system. In the last section, we describe oncogenic mutations that induce NF-kappaB activation in B-cell lymphoma. PMID- 26275875 TI - MAP Kinase Cascades in Antigen Receptor Signaling and Physiology. AB - Mitogen-activated protein kinases (MAPKs) play roles in a cell type and context dependent manner to convert extracellular stimuli to a variety of cellular responses, thereby directing cells to proliferation, differentiation, survival, apoptosis, and migration. Studies of genetically engineered mice or chemical inhibitors specific to each MAPK signaling pathway revealed that MAPKs have various, but non-redundant physiologically important roles among different families. MAPK cascades are obviously integrated in the B cell receptor signaling pathways as critical components to drive B cell-mediated immunity. PMID- 26275876 TI - New species of Ophiostomatales from Scolytinae and Platypodinae beetles in the Cape Floristic Region, including the discovery of the sexual state of Raffaelea. AB - Olea capensis and Rapanea melanophloeos are important canopy trees in South African Afromontane forests. Dying or recently dead individuals of these trees are often infested by Scolytinae and Platypodinae (Curculionidae) beetles. Fungi were isolated from the surfaces of beetles emerging from wood samples and their galleries. Based on micro-morphological and phylogenetic analyses, four fungal species in the Ophiostomatales were isolated. These were Sporothrix pallida and three taxa here newly described as Sporothrix aemulophila sp. nov., Raffaelea vaginata sp. nov. and Raffaelea rapaneae sp. nov. This study represents the first collection of S. pallida, a species known from many environmental samples from across the world, from Scolytinae beetles. S. aemulophila sp. nov. is an associate of the ambrosia beetle Xyleborinus aemulus. R. rapaneae sp. nov. and R. vaginata sp. nov. were associated with a Lanurgus sp. and Platypodinae beetle, respectively, and represent the first Raffaelea spp. reported from the Cape Floristic Region. Of significance is that R. vaginata produced a sexual state analogous with those of Ophiostoma seticolle and O. deltoideosporum that also grouped in our analyses in Raffaelea s. str., to date considered an asexual genus. The morphology of the ossiform ascospores and anamorphs of the three species corresponded and the generic circumscription of Raffaelea is thus emended to accommodate sexual states. The two known species are provided with new combinations, namely Raffaelea seticollis (R.W. Davidson) Z.W. de Beer and T.A. Duong comb. nov. and Raffaelea deltoideospora (Olchow. and J. Reid) Z.W. de Beer and T.A. Duong comb. nov. PMID- 26275877 TI - Acetate kinase-an enzyme of the postulated phosphoketolase pathway in Methylomicrobium alcaliphilum 20Z. AB - Recombinant acetate kinase (AcK) was obtained from the aerobic haloalkalitolerant methanotroph Methylomicrobium alcaliphilum 20Z by heterologous expression in Escherichia coli and purification by affinity chromatography. The substrate specificity, the kinetics and oligomeric state of the His6-tagged AcK were determined. The M. alcaliphilum AcK (2 * 45 kDa) catalyzed the reversible phosphorylation of acetate into acetyl phosphate and exhibited a dependence on Mg(2+) or Mn(2+) ions and strong specificity to ATP/ADP. The enzyme showed the maximal activity and high stability at 70 degrees C. AcK was 20-fold more active in the reaction of acetate synthesis compared to acetate phosphorylation and had a higher affinity to acetyl phosphate (K m 0.11 mM) than to acetate (K m 5.6 mM). The k cat /K m ratios indicated that the enzyme had a remarkably high catalytic efficiency for acetate and ATP formation (k cat/K m = 1.7 * 10(6)) compared to acetate phosphorylation (k cat/K m = 2.5 * 10(3)). The ack gene of M. alcaliphilum 20Z was shown to be co-transcribed with the xfp gene encoding putative phosphoketolase. The Blast analysis revealed the ack and xfp genes in most genomes of the sequenced aerobic methanotrophs, as well as methylotrophic bacteria not growing on methane. The distribution and metabolic role of the postulated phosphoketolase shunted glycolytic pathway in aerobic C1-utilizing bacteria is discussed. PMID- 26275878 TI - ApaL1 urokinase and Taq1 vitamin D receptor gene polymorphisms in first-stone formers, recurrent stone formers, and controls in a Caucasian population. AB - The purpose of this study was to determine differences in genotype distribution and allele frequency of urokinase and vitamin D receptor (VDR) single nucleotide polymorphisms (SNPs) between first-stone formers, recurrent stone formers, and controls in a Caucasian population. A total of 86 first-stone formers, 78 recurrent stone formers, and 167 controls were included. Urokinase and VDR SNPs were tested by gene amplification followed by ApaL1 and Taq1 endonuclease digestion, respectively. Baseline variables, genotype, and allele frequencies were compared between the three groups, using descriptive statistics. Adjusted odds ratios were calculated to estimate the risk for recurrent urolithiasis associated with genotypes. We found that differences in the distribution of ApaL1 SNP and Taq1 SNP genotypes were statistically different between recurrent stone formers and first-stone formers, and between recurrent stone formers and controls. Allele frequency analysis showed that the T allele for ApaL1 SNP and the C allele for Taq1 SNP were significantly associated with recurrent urolithiasis. For Taq1 SNP, logistic regression analysis showed that the C/C genotype was associated with a more than threefold higher risk for recurrent urolithiasis. We conclude that ApaL1 and Taq1 SNPs of the urokinase and VDR genes are associated with recurrent urolithiasis in a Caucasian population. PMID- 26275880 TI - Why Uninsured Free Clinic Patients Don't Apply for Affordable Care Act Health Insurance in a Non-expanding Medicaid State. AB - Even after the introduction of the Patient Protection and Affordable Care Act (ACA), uninsured visits remain high, especially in states that opted out of Medicaid expansion. Since the ACA does not provide universal coverage, free clinics serve as safety nets for the un- or under-insured, and will likely continue serving underserved populations. The purpose of this study is to examine factors influencing intentions to not apply for health insurance via the ACA among uninsured free clinic patients in a state not expanding Medicaid. Uninsured primary care patients utilizing a free clinic (N = 551) completed a self administered survey in May and June 2015. Difficulty obtaining information, lack of instruction to apply, and cost, are major factors influencing intention not to apply for health insurance through the ACA. US born English speakers, non-US born English speakers, and Spanish speakers reported different kinds of perceived barriers to applying for health insurance through the ACA. Age is an important factor impacting individuals' intentions not to apply for health insurance through the ACA, as older patients in particular need assistance to obtain relevant information about the ACA and other resources. A number of unchangeable factors limit the free clinics' ability to promote enrollment of health insurance through the ACA. Yet free clinics could be able to provide some educational programs or the information of resources to patients. In particular, non-US born English speakers, Spanish speakers, and older adults need specific assistance to better understand health insurance options available to them. PMID- 26275881 TI - Perceived Neighborhood Quality and Cancer Screening Behavior: Evidence from the Survey of the Health of Wisconsin. AB - Socioeconomic disparities in colorectal and breast cancer screening persist, partially accounting for disparities in cancer outcomes. Some neighborhood characteristics--particularly area level socioeconomic factors--have been linked to cancer screening behavior, but few studies have examined the relationship between perceived neighborhood quality and screening behavior, which may provide more insight into the ways in which neighborhood environments shape cancer related behaviors. This study examines the relationship between several aspects of the perceived neighborhood environment and breast and colorectal cancer screening behavior among a population-based sample of Wisconsin residents. A sub goal was to compare the relevance of different perceived neighborhood factors for different screening tests. This is a cross-sectional study of 2008-2012 data from the Survey of the Health of Wisconsin, a population-based annual survey of Wisconsin residents. An average risk sample of Black, Hispanic and White women age 50 and older (n = 1265) were selected. Survey regression analyses examined predictors of screening, as well as adherence to screening guidelines. Models controlled for individual socio-demographic information and insurance status. Perceptions of social and physical disorder, including fear of crime and visible garbage, were associated with screening rates. Findings emphasize the particular importance of these factors for colorectal cancer screening, indicating the necessity of improving screening rates in areas characterized by social disorganization, crime, and physical disorder. Additional work should be done to further investigate the pathways that explain the linkage between neighborhood conditions, perceived neighborhood risks and cancer screening behavior. PMID- 26275879 TI - Differences in Host Innate Responses among Coccidioides Isolates in a Murine Model of Pulmonary Coccidioidomycosis. AB - Coccidioides immitis and Coccidioides posadasii are soil-dwelling fungi and the causative agents of coccidioidomycosis, a mycosis endemic to certain semiarid regions in the Americas. The most common route of infection is by inhalation of airborne Coccidioides arthroconidia. Once a susceptible host inhales the conidia, a transition to mature endosporulated spherules can occur within the first 5 days of infection. For this study, we examined the host response in a murine model of coccidioidomycosis during a time period of infection that has not been well characterized. We collected lung tissue and bronchoalveolar lavage fluid (BALF) from BALB/c mice that were infected with a C. immitis pure strain, a C. immitis hybrid strain, or a C. posadasii strain as well as uninfected mice. We compared the host responses to the Coccidioides strains used in this study by assessing the level of transcription of selected cytokine genes in lung tissues and characterized host and fungal proteins present in BALF. Host response varied depending on the Coccidioides strain that was used and did not appear to be overly robust. This study provides a foundation to begin to dissect the host immune response early in infection, to detect abundant Coccidioides proteins, and to develop diagnostics that target these early time points of infection. PMID- 26275883 TI - [Diffusion-weighted imaging]. PMID- 26275882 TI - UCP2 modulates single-channel properties of a MCU-dependent Ca(2+) inward current in mitochondria. AB - The mitochondrial Ca(2+) uniporter is a highly Ca(2+)-selective protein complex that consists of the pore-forming mitochondrial Ca(2+) uniporter protein (MCU), the scaffolding essential MCU regulator (EMRE), and mitochondrial calcium uptake 1 and 2 (MICU1/2), which negatively regulate mitochondrial Ca(2+) uptake. We have previously reported that uncoupling proteins 2 and 3 (UCP2/3) are also engaged in the activity of mitochondrial Ca(2+) uptake under certain conditions, while the mechanism by which UCP2/3 facilitates mitochondrial Ca(2+) uniport remains elusive. This work was designed to investigate the impact of UCP2 on the three distinct mitochondrial Ca(2+) currents found in mitoplasts isolated from HeLa cells, the intermediate- (i-), burst- (b-) and extra-large (xl-) mitochondrial/mitoplast Ca(2+) currents (MCC). Using the patch clamp technique on mitoplasts from cells with reduced MCU and EMRE unveiled a very high affinity of MCU for xl-MCC that succeeds that for i-MCC, indicating the coexistence of at least two MCU/EMRE-dependent Ca(2+) currents. The manipulation of the expression level of UCP2 by either siRNA-mediated knockdown or overexpression changed exclusively the open probability (NPo) of xl-MCC by approx. 38% decrease or nearly a 3-fold increase, respectively. These findings confirm a regulatory role of UCP2 in mitochondrial Ca(2+) uptake and identify UCP2 as a selective modulator of just one distinct MCU/EMRE-dependent mitochondrial Ca(2+) inward current. PMID- 26275884 TI - Erratum. AB - Schoenwald, S. K., Heiblum, N., Saldana, L., & Henggeler, S. W. (2008). The international implementation of Multisystemic Therapy. Evaluation & the Health Professions, 31, 211-225. (DOI: 10.1177/0163278708315925).The acknowledgements section of the article should have included the following conflict of interest statement that was provided by the authors:"Sonja K. Schoenwald and Scott W. Henggeler are board members and stakeholders of MST Services, LLC, a university licensed technology transfer organization." PMID- 26275885 TI - Statin-Ezetimibe Combination Therapy In Diabetic Individuals. PMID- 26275886 TI - Optimization of white matter fiber tractography with diffusional kurtosis imaging. AB - Diffusional kurtosis imaging (DKI) is a clinically feasible diffusion MRI technique for white matter (WM) fiber tractography (FT) with the ability to directly resolve intra-voxel crossing fibers by means of the kurtosis diffusion orientation distribution function (dODF). Here we expand on previous work by exploring properties of the kurtosis dODF and their subsequent effects on WM FT for in vivo human data. For comparison, the results are contrasted with fiber bundle orientation estimates provided by the diffusion tensor, which is the primary quantity obtained from diffusion tensor imaging. We also outline an efficient method for performing DKI-based WM FT that can substantially decrease the computational requirements. The recommended method for implementing the kurtosis ODF is demonstrated to optimize the reproducibility and sensitivity of DKI for detecting crossing fibers while reducing the occurrence of non-physically meaningful, negative values in the kurtosis dODF approximation. In addition, DKI based WM FT is illustrated for different protocols differing in image acquisition times from 48 to 5.3 min. PMID- 26275887 TI - The Fox and the Hedgehog: A Vision of Neuroscience Research in Psychiatry. PMID- 26275888 TI - A comparison of the chemical and liver extract-induced hepatic differentiation of adipose derived stem cells. AB - Adipose-derived stem cells (ADSCs) have been put forward as promising therapeutics for end-stage liver disease (ESLD). In the present study, we compared the effects of defined chemicals and liver extract on the hepatic differentiation of ADSCs. ADSCs were isolated according to the method described in our previously published study. Subsequently, the differentiation of ADSCs was induced separately by chemicals (including hepatic growth factor (HGF), fibroblast growth factor (FGF), and oncostatin M (OSM)) and liver extract (30 MUg/ml) in a total period of 21 d. The efficiency of hepatic differentiation was evaluated by changes in the cell morphology, gene expression, and cellular function. The results showed that the liver extract promoted the hepatic differentiation of ADSCs to a significantly greater extent than the chemicals. In the group of ADSCs treated with liver extract, changes in the cell morphology began sooner, and the expression of alpha-FP and albumin genes was higher than that in the chemically treated group. The ADSCs in both the groups stained positive for anti-alpha trypsin (AAT) and albumin markers. The cells also exhibited glycogen storage capacity. Therefore, we concluded that the liver extract could efficiently induce the differentiation of ADSCs into hepatocyte like cells. This study reveals the potential of mesenchymal stem cell differentiation in the liver extract, which supports further preclinical and clinical research on the application of ADSCs in ESLD treatment. PMID- 26275889 TI - Maribacter flavus sp. nov., isolated from a cyanobacterial culture pond. AB - A Gram-stain-negative, yellow, non-spore-forming, strictly aerobic bacterium, designated C3T, was isolated from a cyanobacterial culture pond. Cells were halophilic, rod-shaped and able to move by gliding. Growth of strain C3T was observed at 15-30 degrees C (optimum 25 degrees C), pH 6.0-9.0 (optimum pH 7.5), and in the presence of 1-7 % (w/v) NaCl (optimum 2-3 %). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain C3T formed a distinct lineage within the family Flavobacteriaceae and exhibited the highest similarity (95.21 %) to the type strains of Maribacter dokdonensis, Maribacter arcticus, Maribacter orientalis and Maribacter stanieri, and 'Maribacter caenipelagi' HD-44. The only isoprenoid quinone present within strain C3T was menaquinone 6 (MK-6). The G+C content of genomic DNA was 41.5 mol%. The major polar lipids were phosphatidylethanolamine and three unidentified lipids. The predominant cellular fatty acids (>5 % of the total fatty acids) were iso-C15 : 1 G, iso-C15 : 0, iso-C15 : 0 3-OH, iso-C17 : 0 3-OH, and summed feature 3 (comprising C16 : 1omega7c and/or C16 : 1omega6c). On the basis of the phenotypic, chemotaxonomic and phylogenetic characteristics, strain C3T represents a novel species of the genus Maribacter, for which the name Maribacter flavus sp. nov. is proposed. The type strain is C3T ( = KCTC 42508T = CGMCC 1.15112T). PMID- 26275890 TI - Lipodermatosclerosis: a clinicopathologic correlation. AB - BACKGROUND: Lipodermatosclerosis (LDS) is a chronic fibrosing panniculitis associated with venous insufficiency. Although LDS is often a clinical diagnosis, it can be confused with other panniculitides. Microscopic examination is therefore essential to support the diagnosis in this condition. Histopathologic changes, however, have not been extensively defined. The purpose of this study was to characterize the histopathologic spectrum of this condition correlated with clinical manifestation. METHODS: A total of 25 cases were collected retrospectively, and the clinical information and histopathologic findings were reviewed. RESULTS: Of 25 patients, the female to male ratio was 4 : 1. The mean age was 54 years (range, 31-74 years). Clinical features were acute in eight (32%), subacute in 12 (48%), and chronic in five (20%). The microscopic study mostly demonstrated vascular stasis changes of varying degrees depending on the age of the lesion. Adipocyte necrosis with thickened septa, extravasation of erythrocytes, and lymphocytic infiltration were major findings in the early lesions. In the chronic lesion, lipomembranous fat necrosis with microcyst formation, vascular stasis changes in subcutaneous tissue, and septal fibrosis were predominant features. Iron deposition or hemosiderin extending to the subcutaneous layer was always seen in all specimens at the subacute and chronic stages. CONCLUSION: The diagnosis of LDS still needs clinicopathologic correlation. The constellation of findings including septal fibrosis, lipomembranous fat necrosis, prominent vascular changes of stasis, and erythrocytic extravasation can be used to define LDS histopathologically. Interestingly, iron deposition in the subcutaneous tissue is a useful finding for this chronic condition. PMID- 26275891 TI - Exome sequencing for prenatal diagnosis of fetuses with sonographic abnormalities. AB - OBJECTIVE: In the absence of aneuploidy or other pathogenic cytogenetic abnormality, fetuses with increased nuchal translucency (NT >= 3.5 mm) and/or other sonographic abnormalities have a greater incidence of genetic syndromes, but defining the underlying pathology can be challenging. Here, we investigate the value of whole exome sequencing in fetuses with sonographic abnormalities but normal microarray analysis. METHOD: Whole exome sequencing was performed on DNA extracted from chorionic villi or amniocytes in 24 fetuses with unexplained ultrasound findings. In the first 14 cases sequencing was initially performed on fetal DNA only. For the remaining 10, the trio of fetus, mother and father was sequenced simultaneously. RESULTS: In 21% (5/24) cases, exome sequencing provided definitive diagnoses (Milroy disease, hypophosphatasia, achondrogenesis type 2, Freeman-Sheldon syndrome and Baraitser-Winter Syndrome). In a further case, a plausible diagnosis of orofaciodigital syndrome type 6 was made. In two others, a single mutation in an autosomal recessive gene was identified, but incomplete sequencing coverage precluded exclusion of the presence of a second mutation. CONCLUSION: Whole exome sequencing improves prenatal diagnosis in euploid fetuses with abnormal ultrasound scans. In order to expedite interpretation of results, trio sequencing should be employed, but interpretation can still be compromised by incomplete coverage of relevant genes. PMID- 26275892 TI - Parathyroidectomy and patient survival in CKD patients. PMID- 26275893 TI - Complement in ANCA-associated glomerulonephritis. AB - Background: Anti-neutrophil cytoplasmic antibodies (ANCA) are found in pauci immune necrotizing crescentic glomerulonephritis. In the past, the role of complement in ANCA-associated vasculitis (AAV) was assumed to be minimal. More recently, however, it was found that blocking the complement cascade in a mouse model of AAV reduces glomerular damage. Immune complex deposits have been found in biopsies from AAV patients. In this study, we questioned whether immune complex formation or deposition may result in complement activation in ANCA associated glomerulonephritis. Methods: ANCA-positive patients from the Limburg Renal Registry were included between 1979 and 2011. Renal histology was documented together with immunoglobulin and complement immunofluorescence. In addition, C3d, properdin, C4d and mannose-binding lectin (MBL) were stained. Electron microscopy was performed. Circulating immune complexes were determined in a subset of patients, as well as C3 allotypes. Results: C3c was found in 78 of 187 renal biopsies (41.7%) divided over 32.3% of proteinase-3 (PR3)-AAV patients and 52.3% of myeloperoxidase (MPO)-AAV patients (P = 0.006), whereas C3d was found positive in 51.1% of PR3-AAV patients and 70.4% of MPO-AAV patients (P = 0.105). C4d was found positive in 70.8%, properdin in 38.7% and MBL in 30.4% of patients. Whereas C4d and MBL positivity was similar between the AGN groups, properdin was more common in biopsies classified as crescentic compared with biopsies classified as focal or mixed. Renal biopsies positive for C3d and/or properdin showed more cellular crescents and less normal glomeruli compared with biopsies negative for C3d and/or properdin (P < 0.05). In 3 out of 43 renal biopsies analysed by electron microscopy, small electron dense deposits were found. In 14 of 46 patients analysed, circulating immune complexes were detectable. No association between histological findings and C3 allotypes was found. Conclusions: In the majority of AAV patients, no immune complex deposits were found in their renal biopsies. C3d, C4d and C5b-9 staining, however, was found to be positive in a majority of analysed renal biopsies. Importantly, C3d and properdin staining was associated with cellular crescents. We hypothesize that local immune complexes are quickly degraded in AAV and therefore not visible by electron microscopy. Our findings are compatible with the hypothesis that complement activation in AAV occurs predominantly via alternative pathway activation. PMID- 26275894 TI - Protein contact prediction by integrating joint evolutionary coupling analysis and supervised learning. AB - MOTIVATION: Protein contact prediction is important for protein structure and functional study. Both evolutionary coupling (EC) analysis and supervised machine learning methods have been developed, making use of different information sources. However, contact prediction is still challenging especially for proteins without a large number of sequence homologs. RESULTS: This article presents a group graphical lasso (GGL) method for contact prediction that integrates joint multi-family EC analysis and supervised learning to improve accuracy on proteins without many sequence homologs. Different from existing single-family EC analysis that uses residue coevolution information in only the target protein family, our joint EC analysis uses residue coevolution in both the target family and its related families, which may have divergent sequences but similar folds. To implement this, we model a set of related protein families using Gaussian graphical models and then coestimate their parameters by maximum-likelihood, subject to the constraint that these parameters shall be similar to some degree. Our GGL method can also integrate supervised learning methods to further improve accuracy. Experiments show that our method outperforms existing methods on proteins without thousands of sequence homologs, and that our method performs better on both conserved and family-specific contacts. AVAILABILITY AND IMPLEMENTATION: See http://raptorx.uchicago.edu/ContactMap/ for a web server implementing the method. CONTACT: j3xu@ttic.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26275896 TI - DSviaDRM: an R package for estimating disease similarity via dysfunctional regulation mechanism. AB - Elucidation of human disease similarities has provided new insights into etiology, disease classification and drug repositioning. Since dysfunctional regulation would be manifested as the decoupling of expression correlation, disease similarity (DS) in terms of dysfunctional regulation mechanism (DRM) could be estimated by using a differential coexpression based approach, which is described in a companion paper. Due to the lack of tools for estimating DS from the viewpoint of DRM in public domain, we implemented an R package 'DSviaDRM' to identify significant DS via DRM based on transcriptomic data. DSviaDRM contains five easy-to-use functions, DCEA, DCpathway, DS, comDCGL and comDCGLplot, for identifying disease relationships and showing common differential regulation information shared by similar diseases. AVAILABILITY AND IMPLEMENTATION: DSviaDRM is available as an R package, with a user's guide and source code, at http://cran.r-project.org/web/packages/DSviaDRM/index.html. CONTACT: yyli@scbit.org or yxli@scbit.org. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26275895 TI - Determining conserved metabolic biomarkers from a million database queries. AB - MOTIVATION: Metabolite databases provide a unique window into metabolome research allowing the most commonly searched biomarkers to be catalogued. Omic scale metabolite profiling, or metabolomics, is finding increased utility in biomarker discovery largely driven by improvements in analytical technologies and the concurrent developments in bioinformatics. However, the successful translation of biomarkers into clinical or biologically relevant indicators is limited. RESULTS: With the aim of improving the discovery of translatable metabolite biomarkers, we present search analytics for over one million METLIN metabolite database queries. The most common metabolites found in METLIN were cross-correlated against XCMS Online, the widely used cloud-based data processing and pathway analysis platform. Analysis of the METLIN and XCMS common metabolite data has two primary implications: these metabolites, might indicate a conserved metabolic response to stressors and, this data may be used to gauge the relative uniqueness of potential biomarkers. AVAILABILITY AND IMPLEMENTATION: METLIN can be accessed by logging on to: https://metlin.scripps.edu CONTACT: siuzdak@scripps.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26275897 TI - Pairwise RNA secondary structure alignment with conserved stem pattern. AB - MOTIVATION: The regulatory functions performed by non-coding RNAs are related to their 3D structures, which are, in turn, determined by their secondary structures. Pairwise secondary structure alignment gives insight into the functional similarity between a pair of RNA sequences. Numerous exact or heuristic approaches have been proposed for computational alignment. However, the alignment becomes intractable when arbitrary pseudoknots are allowed. Also, since non-coding RNAs are, in general, more conserved in structures than sequences, it is more effective to perform alignment based on the common structural motifs discovered. RESULTS: We devised a method to approximate the true conserved stem pattern for a secondary structure pair, and constructed the alignment from it. Experimental results suggest that our method identified similar RNA secondary structures better than the existing tools, especially for large structures. It also successfully indicated the conservation of some pseudoknot features with biological significance. More importantly, even for large structures with arbitrary pseudoknots, the alignment can usually be obtained efficiently. AVAILABILITY AND IMPLEMENTATION: Our algorithm has been implemented in a tool called PSMAlign. The source code of PSMAlign is freely available at http://homepage.cs.latrobe.edu.au/ypchen/psmalign/. PMID- 26275898 TI - Characterization of chemical constituents and rats metabolites of an alkaloidal extract of Alstonia scholaris leaves by liquid chromatography coupled with mass spectrometry. AB - Alstonia scholaris has been used in "Dai" ethnic medicine to treat chronic respiratory diseases for a long history, and the major bioactive constituents are alkaloids. An alkaloidal extract of A. scholaris leaves (AAS) has been developed into an investigational new drug, and has been approved for phase I/II clinical trials by China Food and Drug Administration. However, little is known on the chemical composition and in vivo metabolism of AAS, thus far. In this study, an ultra-high performance liquid chromatography coupled with quadrupole time-of flight mass spectrometry (UHPLC/qTOF-MS) method was established to characterize the chemical constituents of AAS. Samples were separated on an ACQUITY UPLC CSH column (2.1*100mm, 1.7MUm) with acetonitrile and water containing 0.3% formic acid as the mobile phase. On the basis of high-accuracy mass spectral analysis, a total of 35 alkaloids were characterized from AAS, including 11 scholaricine type, 9 vallesamine-type, 12 picrinine-type, and 3 tubotaiwine-type alkaloids. Furthermore, the metabolic pathways of 4 representative alkaloids in rats were studied. They mainly undertook hydroxylation and glucuronidation reactions. Based on the above metabolic pathways, the metabolism of AAS (10mg/kg) in rats after oral administration was studied by LC/MS. A total of 33 compounds in plasma, 40 compounds in urine, and 38 compounds in feces were characterized. The results indicated that scholaricine-type alkaloids could get into circulation more readily than the other types. This is the first systematic study on chemical profiling and metabolites identification of AAS. PMID- 26275899 TI - Traffic pollution at the home address and pregnancy outcomes in Stockholm, Sweden. AB - BACKGROUND: For the past two decades, several studies have reported associations between elevated levels of ambient air pollution and adverse pregnancy outcomes, although with varying conclusions. OBJECTIVES: To examine possible associations between the traffic pollution situation at the home address, for women who did not change address during pregnancy, and three types of pregnancy outcomes: spontaneous preterm delivery, children born small for gestational age (SGA) and pregnancy-induced hypertensive disorders. METHODS: We used data for the Greater Stockholm Area from the Swedish Medical Birth Register to construct a cohort based on all pregnancies conceived between July 1997 and March 2006, n = 100 190. The pregnancy average nitrogen oxide, NOx, levels and annual mean daily vehicles at the home address were used as exposure variables. Mixed-model logistic regression was performed to assess any associations between exposure and outcome. RESULTS: There was an association between elevated traffic pollution exposure during pregnancy and pregnancy-induced hypertensive disorders. A 10 ug/m(3) increase in the pregnancy average NOx level at the home address resulted in an OR of 1.17 (95% CI 1.10 to 1.26). The 2nd to 4th quartiles of NOx were all associated with an increased risk of SGA, but there was no difference in the risk estimate among the higher quartiles. There was a tendency of a higher risk of spontaneous preterm delivery in relation to higher levels of NOx. There was no evidence of an association between vehicle flow, the cruder indicator of traffic pollution, and the studied outcomes in this study. CONCLUSIONS: In this large cohort, there was a fairly strong association between vehicle exhaust levels at the home address and pregnancy-induced hypertensive disorders, after adjustment for important risk factors. PMID- 26275900 TI - Prospective relationships between body weight and physical activity: an observational analysis from the NAVIGATOR study. AB - OBJECTIVES: While bidirectional relationships exist between body weight and physical activity, direction of causality remains uncertain and previous studies have been limited by self-reported activity or weight and small sample size. We investigated the prospective relationships between weight and physical activity. DESIGN: Observational analysis of data from the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) study, a double-blinded randomised clinical trial of nateglinide and valsartan, respectively. SETTING: Multinational study of 9306 participants. PARTICIPANTS: Participants with biochemically confirmed impaired glucose tolerance had annual measurements of both weight and step count using research grade pedometers, worn for 7 days consecutively. Along with randomisation to valsartan or placebo plus nateglinide or placebo, participants took part in a lifestyle modification programme. OUTCOME MEASURES: Longitudinal regression using weight as response value and physical activity as predictor value was conducted, adjusted for baseline covariates. Analysis was then repeated with physical activity as response value and weight as predictor value. Only participants with a response value preceded by at least three annual response values were included. RESULTS: Adequate data were available for 2811 (30%) of NAVIGATOR participants. Previous weight (chi(2)=16.8; p<0.0001), but not change in weight (chi(2)=0.1; p=0.71) was inversely associated with subsequent step count, indicating lower subsequent levels of physical activity in heavier individuals. Change in step count (chi(2)=5.9; p=0.02) but not previous step count (chi(2)=0.9; p=0.34) was inversely associated with subsequent weight. However, in the context of trajectories already established for weight (chi(2) for previous weight measurements 747.3; p<0.0001) and physical activity (chi(2) for previous step count 432.6; p<0.0001), these effects were of limited clinical importance. CONCLUSIONS: While a prospective bidirectional relationship was observed between weight and physical activity, the magnitude of any effect was very small in the context of natural trajectories already established for these variables. TRIAL REGISTRATION NUMBER: NCT00097786. PMID- 26275901 TI - The impact of HPV vaccination on future cervical screening: a simulation study of two birth cohorts in Denmark. AB - OBJECTIVES: To explore the interplay between primary and secondary prevention of cervical cancer by estimating future screening outcomes in women offered human papillomavirus (HPV) vaccination when they were sexually naive. DESIGN: Estimation of outcome of liquid-based cytology screening for a post-HPV vaccination cohort using pre-vaccination screening data combined with HPV vaccination efficacy data reported in the literature. SETTING: Denmark. DATA: The number of screening diagnoses at first screen in a pre-vaccination birth cohort was multiplied by reported risk reductions expected for women who were vaccinated for HPV before sexual debut. All identified studies were reviewed by two authors, and weighted pooled estimates of vaccine efficacies were used. MAIN OUTCOME MEASURES: Proportions of positive and false-positive cervical cytologies and positive predictive value (PPV) were calculated using cervical intraepithelial neoplasia (CIN) grade 2+ and 3+ as cut-off values. RESULTS: The proportion of positive screening tests was reduced from 8.7% before vaccination to 6.5% after vaccination, and the proportion of false-positive screening tests using CIN2+ as a cut-off was reduced from 5.5% pre-vaccination to 4.3% post-vaccination, and using CIN3+ as a cut-off from 6.2% to 4.7%. PPVs were reduced from 23% to 19% (cut-off CIN2+), and from 14% to 12% (cut-off CIN3+). CONCLUSIONS: In our calculations, the proportion of positive screening results with liquid-based cytology will be reduced as a consequence of HPV vaccination, but the reduction is small, and the expected decline in PPV is very limited. In this situation, the information general practitioners will have to provide to their patients will be largely unchanged. PMID- 26275902 TI - What interventions increase commuter cycling? A systematic review. AB - OBJECTIVE: To identify interventions that will increase commuter cycling. SETTING: All settings where commuter cycling might take place. PARTICIPANTS: Adults (aged 18+) in any country. INTERVENTIONS: Individual, group or environmental interventions including policies and infrastructure. PRIMARY AND SECONDARY OUTCOME MEASURES: A wide range of 'changes in commuter cycling' indicators, including frequency of cycling, change in workforce commuting mode, change in commuting population transport mode, use of infrastructure by defined populations and population modal shift. RESULTS: 12 studies from 6 countries (6 from the UK, 2 from Australia, 1 each from Sweden, Ireland, New Zealand and the USA) met the inclusion criteria. Of those, 2 studies were randomised control trials and the remainder preintervention and postintervention studies. The majority of studies (n=7) evaluated individual-based or group-based interventions and the rest environmental interventions. Individual-based or group-based interventions in 6/7 studies were found to increase commuter cycling of which the effect was significant in only 3/6 studies. Environmental interventions, however, had small but positive effects in much larger but more difficult to define populations. Almost all studies had substantial loss to follow-up. CONCLUSIONS: Despite commuter cycling prevalence varying widely between countries, robust evidence of what interventions will increase commuter cycling in low cycling prevalence nations is sparse. Wider environmental interventions that make cycling conducive appear to reach out to hard to define but larger populations. This could mean that environmental interventions, despite their small positive effects, have greater public health significance than individual-based or group based measures because those interventions encourage a larger number of people to integrate physical activity into their everyday lives. PMID- 26275903 TI - Cohort profile: systemic lupus erythematosus in Sweden: the Swedish Lupus Linkage (SLINK) cohort. AB - PURPOSE: A cohort of individuals with systemic lupus erythematosus (SLE) was identified through linkage of several national registers to investigate important epidemiological questions using not only population-based data to minimise selection bias, but also to identify matched comparators from the general population to serve as controls. This cohort was established to overcome the general dearth of data in SLE epidemiology. PARTICIPANTS: All individuals registered in Sweden with a personal identity number and who have obtained medical care at any hospital or public non-primary outpatient specialist care with suspected SLE were identified. Inpatient register data date back to the 1960s, although complete national coverage of the inpatient register was achieved in 1987. In 2001, the outpatient component was also added to the register, representing the entire country of Sweden. For each suspected individual with SLE, up to five individuals from the general population were identified and matched on sex, birth year and county of residence. FINDINGS TO DATE: We have linked this study population to a number of national and quality registers in Sweden to identify first-degree relatives, deaths, births, dispensed prescriptions, comorbidities and disease end points, such as stroke and cancer, as well as basic health economic data. We found geographic variability in the prevalence of SLE by county. We have also shown that being first-born confers a reduced odds of having SLE in childhood and early adulthood. FUTURE PLANS: In addition to updating the national register linkage with several more years of follow-up data, we are adding several quality registers in Sweden, including the Tuberculosis register and the Social Insurance Office database. While these updates are ongoing and additional follow-up accumulates, we are studying a number of outcomes in SLE, including stroke, pregnancy and death. We will continue to present findings at scientific conferences and in the peer-reviewed literature. PMID- 26275904 TI - Comparative genome analysis of Mycoplasma pneumoniae. AB - BACKGROUND: Mycoplasma pneumoniae is a common pathogen that causes upper and lower respiratory tract infections in people of all ages, responsible for up to 40% of community-acquired pneumonias. It also causes a wide array of extrapulmonary infections and autoimmune phenomena. Phylogenetic studies of the organism have been generally restricted to specific genes or regions of the genome, because whole genome sequencing has been completed for only 4 strains. To better understand the physiology and pathogenicity of this important human pathogen, we performed comparative genomic analysis of 15 strains of M. pneumoniae that were isolated between the 1940s to 2009 from respiratory specimens and cerebrospinal fluid originating from the USA, China and England. RESULTS: Illumina MiSeq whole genome sequencing was performed on the 15 strains and all genome sequences were completed. Results from the comparative genomic analysis indicate that although about 1500 SNP and indel variants exist between type1 and type 2 strains, there is an overall high degree of sequence similarity among the strains (>99% identical to each other). Within the two subtypes, conservation of most genes, including the CARDS toxin gene and arginine deiminase genes, was observed. The major variation occurs in the P1 and ORF6 genes associated with the adhesin complex. Multiple hsdS genes (encodes S subunit of type I restriction enzyme) with variable tandem repeat copy numbers were found in all 15 genomes. CONCLUSIONS: These data indicate that despite conclusions drawn from 16S rRNA sequences suggesting rapid evolution, the M. pneumoniae genome is extraordinarily stable over time and geographic distance across the globe with a striking lack of evidence of horizontal gene transfer. PMID- 26275905 TI - Clinical excellence in nephrology: Examples from the published literature. AB - BACKGROUND: Provision of exceptional medical care is a goal for the medical profession because this is what the public needs and deserves. Academic medical centers that value excellent clinicians may have the best chance to recruit and retain these faculty members. When our institution hoped to launch the Miller Coulson Academy of Clinical Excellence to measure and reward master clinicians, a critical first step was to use rigorous methods to develop a definition of clinical excellence. Published papers have illustrated that this general definition of clinical excellence is applicable to fields of psychiatry, cardiology, and pediatrics. In this manuscript, we apply the definition of clinical excellence to nephrology. Using the same framework, we reviewed the literature to find clinical cases and exemplary nephrologists that highlight the specific domains. This collection of reports in nephrology illustrates that the definition of clinical excellence set forth by the Miller Coulson Academy is highly applicable to physicians caring for individuals with kidney disease. Relating the definition of clinical excellence to renal medicine is worthwhile in that it can help to exemplify the model to which physicians and trainees may seek to aspire. KEY MESSAGE: Many examples of clinical excellence in renal medicine can be found in the published medical literature. The domains of clinical excellence, described by the Miller-Coulson Academy of Clinical Excellence, apply very well to the field of nephrology. PMID- 26275906 TI - Competition is not necessarily a barrier to community mobilisation among sex workers: an intervention planning assessment from Zimbabwe. AB - BACKGROUND: Community mobilization among female sex workers (SWs) is recognized as an effective strategy to empower SWs and increase their uptake of health services. Activities focus on increasing social cohesion between SWs by building trust, strengthening networks, and encouraging shared efforts for mutual gain. Several studies, however, suggest that high levels of interpersonal competition between SWs can pose a barrier to collective action and support. We conducted a study to examine levels of perceived competition between SWs in Mutare, Hwange and Victoria Falls in Zimbabwe in order to inform development of a community based intervention for HIV prevention and treatment. This paper focuses on our qualitative findings and their implications for the design of HIV programming in the Zimbabwean context. METHODS: Following a respondent driven sampling (RDS) survey, we explored issues related to social cohesion amongst SWs in Mutare, Hwange and Victoria Falls through in-depth interviews conducted with 22 SWs. Interviews examined dynamics of SWs' relationships and extent of social support, and were analyzed using thematic content analysis using the constant comparative method. Findings are contextualised against descriptive data extracted from the survey, which was analysed using Stata 12, adjusting for RDS. RESULTS: Across all sites, women described protecting each other at night, advising each other about violent or non-paying clients, and paying fines for each other following arrest. In Mutare, women gave additional examples, including physically attacking problem clients, treatment adherence support and shared saving schemes. However, interviews also highlighted fierce competition between women and deep mistrust. This reflects the reported mix of competition and support from the survey of 836 women (Mutare n = 370, Hwange n = 237, Victoria Falls n = 229). In Mutare, 92.8 % of SWs agreed there was a lot of competition; 87.9 % reported that SWs support each other. This contrasted with Victoria Falls and Hwange where fewer agreed there was competition between SWs (70.5 % and 78.0 %), but also fewer reported that SWs support each other at work (55.2 % and 51.2 %). CONCLUSIONS: Women reported being most likely to support each other when confronted with serious danger but maintained high levels of competition for clients, suggesting competition at work does not represent a barrier to support. Examples of practical assistance between SWs provide entry points for our planned community mobilization activities, which aim to broaden trust and support among SWs while acknowledging their professional competition. PMID- 26275907 TI - How important is randomisation in a stepped wedge trial? AB - In cluster randomised trials, randomisation increases internal study validity. If enough clusters are randomised, an unadjusted analysis should be unbiased. If a smaller number of clusters are included, stratified or matched randomisation can increase comparability between trial arms. In addition, an adjusted analysis may be required; nevertheless, randomisation removes the possibility for systematically biased allocation and increases transparency. In stepped wedge trials, clusters are randomised to receive an intervention at different start times ('steps'), and all clusters eventually receive it. In a recent study protocol for a 'modified stepped wedge trial', the investigators considered randomisation of the clusters (hospital wards), but decided against it for ethical and logistical reasons, and under the assumption that it would not add much to the rigour of the evaluation. We show that the benefits of randomisation for cluster randomised trials also apply to stepped wedge trials. The biggest additional issue for stepped wedge trials in relation to parallel cluster randomised trials is the need to control for secular trends in the outcome. Analysis of stepped wedge trials can in theory be based on 'horizontal' or 'vertical' comparisons. Horizontal comparisons are based on measurements taken before and after the intervention is introduced in each cluster, and are unbiased if there are no secular trends. Vertical comparisons are based on outcome measurements from clusters that have switched to the intervention condition and those from clusters that have yet to switch, and are unbiased under randomisation since at any time point, which clusters are in intervention and control conditions will have been determined at random. Secular outcome trends are a possibility in many settings. Many stepped wedge trials are analysed with a mixed model, including a random effect for cluster and fixed effects for time period to account for secular trends, thereby combining both vertical and horizontal comparisons of intervention and control clusters. The importance of randomisation in a stepped wedge trial is that the effects of time can be estimated from the data, and bias from secular trends that would otherwise arise can be controlled for, provided the trends are correctly specified in the model. PMID- 26275909 TI - Elimination of Plasmodium falciparum in an area of multi-drug resistance. AB - BACKGROUND: Resistance to the artemisinin derivatives in Plasmodium falciparum has emerged in Cambodia and is now spreading throughout South-East Asia. The rapid elimination of P. falciparum seems to be the only viable option to avoid a public health disaster but this is difficult because even in low transmission settings many residents have asymptomatic parasitaemias. METHODS: In response to a large number of malaria cases reported in three remote villages on the Thai Myanmar border where malaria is endemic and the disease is seasonal, surveys were conducted using an ultra-sensitive qPCR assay (LOD 22 parasites per mL). In one of the villages where it was feasible, mass anti-malarial drug administration was proposed to the population as a potential solution, and this was adopted. RESULTS: In the three villages 204/356 (57.3 %), 212/385 (55.1 %) and 195/286 (68.2 %) of the resident populations were positive by qPCR (approximately one third P. falciparum and two-thirds P. vivax). Of those positive for P. falciparum 62 % carried single point mutations in the P. falciparum kelch protein (a marker of artemisinin resistance). In one of the villages 217 of 674 inhabitants received at least one dose of dihydroartemisinin-piperaquine chemoprevention in June 2012, 155 (71.4 %) received two consecutive months, and 98 (45.2 %) received three treatment doses. The chemoprevention was generally well tolerated. The sub microscopic reservoir of P. falciparum malaria was eliminated during the six month follow-up period (prevalence fell from 7 to 0 %); P. vivax malaria persisted (prevalence fell from 35 to 8 %). From June to October 2012 (rainy season) the number of clinical episodes of P. falciparum was six times lower (46), than during the same period in the previous year (290). CONCLUSION: Mass drug administration with dihydroartemisinin-piperaquine may be an effective strategy to eliminate P. falciparum rapidly where multi-drug resistance is present. PMID- 26275908 TI - Rapid microbiological screening for tuberculosis in HIV-positive patients on the first day of acute hospital admission by systematic testing of urine samples using Xpert MTB/RIF: a prospective cohort in South Africa. AB - BACKGROUND: Autopsy studies of HIV/AIDS-related hospital deaths in sub-Saharan Africa reveal frequent failure of pre-mortem diagnosis of tuberculosis (TB), which is found in 34-64 % of adult cadavers. We determined the overall prevalence and predictors of TB among consecutive unselected HIV-positive adults requiring acute hospital admission and the comparative diagnostic yield obtained by screening urine and sputum samples obtained on day 1 of admission with Xpert MTB/RIF (Xpert). METHODS: To determine overall TB prevalence accurately, comprehensive clinical sampling (sputum, urine, blood plus other relevant samples) was done and TB was defined by detection of Mycobacterium tuberculosis in any sample using Xpert and/or mycobacterial liquid culture. To evaluate a rapid screening strategy, we compared the diagnostic yield of Xpert testing sputum samples and urine samples obtained with assistance from a respiratory study nurse in the first 24 h of admission. RESULTS: Unselected HIV-positive acute adult new medical admissions (n = 427) who were not receiving TB treatment were enrolled irrespective of clinical presentation or symptom profile. From 2,391 cultures and Xpert tests done (mean, 5.6 tests/patient) on 1,745 samples (mean, 4.1 samples/patient), TB was diagnosed in 139 patients (median CD4 cell count, 80 cells/MUL). TB prevalence was very high (32.6 %; 95 % CI, 28.1-37.2 %; 139/427). However, patient symptoms and risk factors were poorly predictive for TB. Overall, >=1 non-respiratory sample(s) tested positive in 115/139 (83 %) of all TB cases, including positive blood cultures in 41/139 (29.5 %) of TB cases. In the first 24 h of admission, sputum (spot and/or induced samples) and urine were obtainable from 37.0 % and 99.5 % of patients, respectively (P <0.001). From these, the proportions of total TB cases (n = 139) that were diagnosed by Xpert testing sputum, urine or both sputum and urine combined within the first 24 h were 39/139 (28.1 %), 89/139 (64.0 %) and 108/139 (77.7 %) cases, respectively (P <0.001). CONCLUSIONS: The very high prevalence of active TB and its non-specific presentation strongly suggest the need for routine microbiological screening for TB in all HIV-positive medical admissions in high-burden settings. The incremental diagnostic yield from Xpert testing urine was very high and this strategy might be used to rapidly screen new admissions, especially if sputum is difficult to obtain. PMID- 26275911 TI - A layered electrospun and woven surgical scaffold to enhance endogenous tendon repair. AB - Surgical reattachments of tendon to bone in the rotator cuff are reported to fail in around 40% of cases. There are no adequate solutions to improve tendon healing currently available. Electrospun, sub-micron materials, have been extensively studied as scaffolds for tendon repair with promising results, but are too weak to be surgically implanted or to mechanically support the healing tendon. To address this, we developed a bonding technique that enables the processing of electrospun sheets into multi-layered, robust, implantable fabrics. Here, we show a first prototype scaffold created with this method, where an electrospun sheet was reinforced with a woven layer. The resulting scaffold presents a maximum suture pull out strength of 167N, closely matched with human rotator cuff tendons, and the desired nanofibre-mediated bioactivity in vitro and in vivo. This type of scaffold has potential for broader application for augmenting other soft tissues. PMID- 26275910 TI - Active immunization against complement factor C5a: a new therapeutic approach for Alzheimer's disease. AB - BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by neuronal loss due to amyloid beta aggregations, neurofibrillary tangles, and prominent neuroinflammation. Recently, interference with neuroinflammation as a new therapeutic approach for AD treatment gained great interest. Microglia cells, one of the major contributors in neuroinflammation, are activated in response to misfolded proteins such as amyloid beta and cell debris leading to a sustained release of pro-inflammatory mediators. Especially, complement factor C5a and its receptor have been found to be up-regulated in microglia in the immediate surroundings of cerebral amyloid plaques and blocking of C5aR resulted in a reduction of pathological markers in a model of AD. Here, we investigate the effect of active vaccination against the complement factor C5a to interfere with neuroinflammation and neuropathologic alterations in a mouse model of AD. METHODS: Short antigenic peptides AFF1 and AFF2, which mimic a C terminal epitope of C5a, were selected and formulated to vaccines. These vaccines are able to induce a highly specific antibody response to the target protein C5a. Tg2576 mice, a common model of AD, were immunized with these two C5a-peptide vaccines and the induced immune response toward C5a was analyzed by ELISA and Western blot analysis. The influence on memory retention was assessed by a contextual fear conditioning test. Microglia activation and amyloid plaque deposition in the brain was visualized by immunohistochemistry. RESULTS: Both C5a targeting vaccines were highly immunogenic and induced sustained antibody titers against C5a. Tg2576 mice vaccinated at early stages of the disease showed significantly improved contextual memory accompanied by the reduction of microglia activation in the hippocampus and cerebral amyloid plaque load compared to control mice. Late-stage immunization also showed a decrease in the number of activated microglia, and improved memory function, however, had no influence on the amyloid beta load. CONCLUSION: C5a-peptide vaccines represent a safe and well tolerated immunotherapy, which is able to induce a strong and specific immune response against the pro-inflammatory molecule C5a. In a mouse model of AD, C5a peptide vaccines reduce microglia activation and thus neuroinflammation, which is supposed to lead to reduced neuronal dysfunction and AD symptomatic decline. PMID- 26275912 TI - Cholesterol level in non-insertional Achilles tendonopathy. AB - Familial hypercholesterolaemia is an autosomal dominant disease, with a prevalence of 1 in 500, where lipid deposits occur in the skin, tendons (particularly Achilles tendon) and arteries. It has a high risk of early coronary artery disease and mortality but is treatable with cholesterol lowering strategies if patients are diagnosed early. Studies in patients attending lipid clinics have shown that half the patients may have suffered from Achilles tendon symptoms 20 years earlier and it has been proposed that all patients presenting with Achilles tendon pain should have a serum cholesterol test. All consecutive patients seen in an adult foot and ankle clinic with non-insertional Achilles tendonopathy between April 2012 and March 2014 had their serum cholesterol measured. Only one patient in 83 (p=0.19) was diagnosed with heterozygous familial hypercholesterolaemia but 3 relatives of the proband patient were also diagnosed by cascade testing. Measurement of cholesterol in all patients presenting with achillodynia does not seem to be justified but the literature suggests that it should probably be considered in patients with bilateral extensive disease or those who give a history of intermittent episodes of severe pain lasting a few days. PMID- 26275913 TI - Impoverished descriptions of familiar routes in three cases of hippocampal/medial temporal lobe amnesia. AB - Recent research has challenged classic theories of hippocampal function in spatial memory with findings that the hippocampus may be necessary for detailed representations of environments learned long ago, but not for remembering the gist or schematic aspects that are sufficient for navigating within those environments (Rosenbaum et al., 2000; Rosenbaum, Winocur, Binns, & Moscovitch, 2012). We aimed to probe further distinctions between detailed and schematic representations of familiar environments in three cases of hippocampal/medial temporal lobe (MTL) amnesia by testing them on a route description task and mental navigation tasks that assess the identity and location of landmarks, and distances and directions between them. The amnesic cases could describe basic directions along known, imagined routes, estimate distance and direction between well-known landmarks, and produce sketch maps with accurate layouts, suggestive of intact schematic representations. However, findings that their route descriptions lack richness of detail, along with impoverished sketch maps and poor landmark recognition, substantiates previous findings that detailed representations are hippocampus-dependent. PMID- 26275914 TI - Pervasive refusal syndrome - A clinical challenge. AB - Pervasive refusal syndrome is described as a condition comprising varying degrees of refusal across several domains; social withdrawal; resistance to treatment and is potentially life threatening with no detectable organic cause. Female predominance, refusal to eat with low weight, body image distortion, depressive features, premorbid personality issues similar to eating disorders have been noted, with 67% cases having complete recovery. In this paper, we describe what is probably the first case reported from India, of a child, who presented with neuropsychiatric symptoms, and treated with electroconvulsive therapy along with medications, but, sadly had a fatal outcome. PMID- 26275915 TI - Establishment of the upper reference limit for thyroid peroxidase autoantibodies according to the guidelines proposed by the National Academy of Clinical Biochemistry: comparison of five different automated methods. AB - AIM OF THE STUDY: The estimation of the upper reference limit (URL) for autoantibodies against thyroid peroxidase (TPOAbs) is a controversial issue, because of an uncertainty associated with the criteria used to correctly define the reference population. In addition, the URL of TPOAbs is method-dependent and often arbitrarily established in current laboratory practice. The aim of this study was to determine the reference limits of TPOAbs in a male sample according to the National Academy of Clinical Biochemistry (NACB) guidelines, and to compare them with those obtained in a female group, for five third-generation commercial-automated immunoassay (IMA) platforms. METHODS: 120 healthy males and 120 healthy females with NACB-required characteristics (younger than 30 years, TSH between 0.5 and 2.0 mIU/L, normal thyroid ultrasound, absence of thyroid disease and absence of other autoimmune diseases) were studied. Sera were analyzed for TPOAbs concentration using five IMA methods applied in automated analyzers: Immulite 2000 XPi (IMM); Maglumi 2000 Plus (MAG); Kryptor Compact Plus (KRY); Phadia 250 (PHA) and Liaison XL (LIA). RESULTS: A statistically significant difference (p < 0.05) between medians in male and female groups was observed for PHA (2.6 and 3.1 IU/mL, respectively) but not for the other four methods. Scatter plots of TPOAbs values revealed a wide dispersion with very different coefficients of variation between the five methods, varying from 48.6 % for KRY in females to 126.3 % for MAG in females. The URLs differed in males and females according to the method: 28.7 and 29.0 IU/mL for IMM, 24.6 and 25.4 IU/mL for MAG, 6.4 and 6.9 IU/mL for KRY, 8.3 and 10.0 IU/mL for PHA and 14.2 and 17.9 IU/mL for LIA, respectively. Such URLs were lower than those stated by the manufacturers except for LIA in females. The difference between URLs ranged from a minimum of 11.3 % (LIA in males) to a maximum of 66.8 % (PHA in males). CONCLUSIONS: Differences in URLs could result from the different coating preparations of the TPO antigen (purified native or recombinant) on solid phase, which affect the proper exposure of the immunodominant epitopes recognized by the polyclonal antibodies present in serum of patients with autoimmune thyroid disease (AITD). Based on these findings, we suggest to overcome the proposal of the NACB guidelines which recommend to involve a single group of young male subjects, and propose, instead, to utilize two distinct groups: one of males and one of females. This new proposal removes the apparent contrast of an all-male reference group for a disease (such as AITD) that affects mainly females. However, in spite of the harmonization among methods provided by the use of an international standard preparation, the wide dispersion of quantitative results still observed in this study suggests the need for further efforts to better understand the cause of these discrepancies, focusing on TPO antigen preparations as the possible source of variability among different assays. PMID- 26275916 TI - Near-complete 1H, 13C, 15N resonance assignments of dimethylsulfoxide-denatured TGFBIp FAS1-4 A546T. AB - The transforming growth factor beta induced protein (TGFBIp) is a major protein component of the human cornea. Mutations occurring in TGFBIp may cause corneal dystrophies, which ultimately lead to loss of vision. The majority of the disease causing mutations are located in the C-terminal domain of TGFBIp, referred as the fourth fascilin-1 (FAS1-4) domain. In the present study the FAS1-4 Ala546Thr, a mutation that causes lattice corneal dystrophy, was investigated in dimethylsulfoxide using liquid-state NMR spectroscopy, to enable H/D exchange strategies for identification of the core formed in mature fibrils. Isotope labeled fibrillated FAS1-4 A546T was dissolved in a ternary mixture 95/4/1 v/v/v% dimethylsulfoxide/water/trifluoroacetic acid, to obtain and assign a reference 2D (1)H-(15)N HSQC spectrum for the H/D exchange analysis. Here, we report the near complete assignments of backbone and aliphatic side chain (1)H, (13)C and (15)N resonances for unfolded FAS1-4 A546T at 25 degrees C. PMID- 26275917 TI - Backbone resonance assignment of N15, N30 and D10 T cell receptor beta subunits. AB - The alphabetaT Cell receptor (TCR) governs T cell immunity through its interaction with peptide bound to major histocompatibility complex molecules (pMHC). Previously, soluble ectodomain constructs have been used to elucidate the binding mode of the TCR for the MHC. However, the full heterodimeric alphabetaTCR has proven difficult to produce reproducibly in recombinant systems to the extent seen in the routine production of novel antibodies. Particularly, the route of production in E. coli, which is most convenient for isotopic labeling of proteins, is challenging for a wide range of alphabetaTCR, including N15alphabeta, N30alphabeta, but not D10alphabeta. With the aim of understanding the TCR-pMHC interaction through the use of dynamic binding measurements, we set out to produce TCRbeta subunits with which we could investigate binding with pMHC. The TCRbeta constructs are more readily produced and refolded than their alphabeta counterparts and have proven to be an effective model of preTCR in pMHC binding studies. As a first step towards characterizing potential interactions with protein ligands, we have assigned the backbone resonances of three TCRbeta subunits, N15beta, N30beta and D10beta. PMID- 26275918 TI - Evaluative conditioning of positive and negative valence affects P1 and N1 in verbal processing. AB - The present study examined the effect of contextual learning on the neural processing of previously meaningless pseudowords. During an evaluative conditioning session on 5 consecutive days, participants learned to associate 120 pseudowords with either positive, neutral or negative pictures. In a second session, participants were presented all conditioned pseudowords again together with 40 new pseudowords in a recognition memory task while their event-related potentials (ERPs) were recorded. The behavioral data confirm successful learning of pseudoword valence. At the neural level, early modulations of the ERPs are visible at the P1 and the N1 components discriminating between positively and negatively conditioned pseudowords. Differences to new pseudowords were visible at later processing stages as indicated by modulations of the LPC. These results support a contextual learning hypothesis that is able to explain very early emotional ERP modulations in visual word recognition. Source localization indicates a role of medial-frontal brain regions as a likely origin of these early valence discrimination signals which are discussed to promote top-down signals to sensory processing. PMID- 26275919 TI - Atypical cortical gyrification in adolescents with histories of heavy prenatal alcohol exposure. AB - Prenatal alcohol exposure can adversely affect brain development, although little is known about the effects of prenatal alcohol exposure on gyrification. Gyrification reflects cortical folding complexity and is a process by which the surface of the brain creates sulci and gyri. Prior studies have shown that prenatal alcohol exposure is associated with reduced gyrification in childhood, but no studies have examined adolescents. Subjects (12-16 years) comprised two age-equivalent groups: 30 adolescents with histories of heavy prenatal alcohol exposure (AE) and 19 non-exposed controls (CON). A T1-weighted image was obtained for all participants. Local gyrification index (LGI) was estimated using FreeSurfer. General linear models were used to determine between group differences in LGI controlling for age and sex. Age-by-group interactions were also investigated while controlling for sex. The AE group displayed reduced LGI relative to CON in the bilateral superior parietal region, right postcentral region, and left precentral and lateral occipital regions (ps<.001). Significant age-by-group interactions were observed in the right precentral and lateral occipital regions, and in the left pars opercularis and inferior parietal regions (ps<.01). The AE group showed age-related reductions in gyrification in all regions whereas the CON group showed increased gyrification with age in the lateral occipital region only. While cross-sectional, the age-related reduction in gyrification observed in the AE group suggests alterations in cortical development throughout adolescence and provides further insight into the pathophysiology and brain maturation of adolescents prenatally exposed to alcohol. PMID- 26275920 TI - Inguinal hernia repair with Parietex ProGrip mesh causes minimal discomfort and allows early return to normal activities. AB - BACKGROUND: The type of inguinal hernia repair used depends on many factors but predominantly the surgeon's training, interpretation of the literature, and personal preference. This prospective cohort study describes a consecutive series of open mesh inguinal hernia repairs (modified Lichtenstein technique) performed as an outpatient procedure using 2 different mesh types. METHODS: Analysis was undertaken on 540 consecutive patients who underwent inguinal hernia repair between January 2007 and December 2012. Short-term outcomes were compared between those repaired with conventional polypropylene mesh and those with Parietex ProGrip mesh. RESULTS: Most patients were male (89%) and the mean age was 63 years. The median operative time was 50 minutes for unilateral hernias and 90 minutes for bilateral hernias. The use of Parietex ProGrip mesh reduced the operative time to 40 minutes for unilateral hernias (P < .01) and 75 minutes for bilateral hernias (P < .01). After unilateral hernia repair, 88% of the patients were discharged home within 4 hours of operation. There was no mortality and the overall complication rate was 7.4%. One patient developed a pulmonary embolus but the remainder of the complications were minor. Twenty-four hours postoperatively, 74% of the patients were either totally pain free or had minimal discomfort. At 4 weeks, 97% of the patients were either pain free or had minimal discomfort. Patients who underwent unilateral inguinal hernia repair with Parietex ProGrip mesh had the most rapid return to normal activities (10 vs 14 days, P < .04). CONCLUSIONS: Open anterior inlay mesh repair is safe and results in minimal postoperative pain and early return to normal activities. ProGrip mesh resulted in a shorter operative time and more rapid return to normal activities compared with polypropylene mesh (10 vs 14 days). PMID- 26275921 TI - Predictive factors for sentinel lymph nodes and non-sentinel lymph nodes metastatic involvement: a database study of 1,041 melanoma patients. AB - BACKGROUND: Sentinel lymph node (SLN) biopsy may identify patients who may need completion lymphadenectomy and adjuvant therapy. METHODS: Univariate and multivariate analysis were conducted for SLN status in a prospective cohort of 1,041 patients. A biopsy was recommended for melanoma greater than or equal to 1 mm thick or greater than or equal to .75 mm with poor prognostic features. RESULTS: For sentinel node status, mitotic rate is very significant in univariate analysis. In multivariate analysis, Breslow, lymphovascular invasion, and primary site were significant. Breslow thickness greater than or equal to 2 mm and SLN with macroscopic burden greater than or equal to 2 mm are the only statistically significant variables predicting the non-SLN status in multivariate analysis. CONCLUSIONS: The data confirm the importance of Breslow, lymphovascular invasion, and body site for SLN status. The cutoff of 2 mm for tumor load in SLN appears to be a simple technique to find the high-risk patients with further lymph node disease. PMID- 26275922 TI - Comparative mapping of host-pathogen protein-protein interactions. AB - Pathogens usurp a variety of host pathways via protein-protein interactions to ensure efficient pathogen replication. Despite the existence of an impressive toolkit of systematic and unbiased approaches, we still lack a comprehensive list of these PPIs and an understanding of their functional implications. Here, we highlight the importance of harnessing genetic diversity of hosts and pathogens for uncovering the biochemical basis of pathogen restriction, virulence, fitness, and pathogenesis. We further suggest that integrating physical interaction data with orthogonal types of data will allow researchers to draw meaningful conclusions both for basic and translational science. PMID- 26275923 TI - Morc1 knockout evokes a depression-like phenotype in mice. AB - Morc1 gene has recently been identified by a DNA methylation and genome-wide association study as a candidate gene for major depressive disorder related to early life stress in rodents, primates and humans. So far, no transgenic animal model has been established to validate these findings on a behavioral level. In the present study, we examined the effects of a Morc1 loss of function mutation in female C57BL/6N mice on behavioral correlates of mood disorders like the Forced Swim Test, the Learned Helplessness Paradigm, O-Maze and Dark-Light-Box. We could show that Morc1(-/-) mice display increased depressive-like behavior whereas no behavioral abnormalities regarding locomotor activity or anxiety-like behavior were detectable. CORT plasma levels did not differ significantly between Morc1(-/-) mice and their wildtype littermates, yet - surprisingly - total Bdnf mRNA-levels in the hippocampus were up-regulated in Morc1(-/-) animals. Although further work would be clarifying, Morc1(-/-) mice seem to be a promising epigenetically validated mouse model for depression associated with early life stress. PMID- 26275924 TI - A behavioral and histological comparison of fluid percussion injury and controlled cortical impact injury to the rat sensorimotor cortex. AB - Our primary goal was to evaluate the behavioral and histological outcome of fluid percussion injury (FPI) and cortical contusion injury (CCI) to the sensorimotor cortex (SMC). The SMC has been used to evaluate neuroplasticity following CCI, but has not been extensively examined with FPI. In both the CCI and FPI models, a mechanical force of 4mm in diameter was applied over the SMC, allowing for a direct comparison to measure the relative rates of histology and recovery of function in these models. Gross behavioral deficits were found on the sensory task (tactile adhesive removal task) and multiple motor assessments (forelimb asymmetry task, forelimb placing task, and rotorod). These sensorimotor deficits occurred in the absence of cognitive deficits in the water maze. The CCI model creates focal damage with a localized injury wheras the FPI model creates a more diffuse injury causing widespread damage. Both behavioral and histological deficits ensued following both models of injury to the SMC. The neuroplastic changes and ease at which damage to this area can be measured behaviorally make this an excellent location to assess traumatic brain injury (TBI) treatments. No injury model can completely mimic the full spectrum of human TBI and any potential treatments should be validated across both focal and diffuse injury models. Both of these injury models to the SMC produce severe and enduring behavioral deficits, which are ideal for evaluating treatment options. PMID- 26275926 TI - Differential activation of accumbens shell and core dopamine by sucrose reinforcement with nose poking and with lever pressing. AB - In order to investigate the role of modus operandi in the changes of nucleus accumbens (NAc) dopamine (DA) transmission in sucrose reinforcement, extracellular DA was monitored by microdialysis in the NAc shell and core of rats trained on a fixed-ratio 1 schedule to respond for sucrose pellets by nose poking and lever pressing respectively. After training, rats were tested on three different sessions: sucrose reinforcement, extinction and passive sucrose presentation. In rats responding by nose poking dialysate DA increased in the shell but not in the core under reinforced as well as under extinction sessions. In contrast, in rats responding by lever pressing dialysate DA increased both in the accumbens shell and core under reinforced and extinction sessions. Response non-contingent sucrose presentation increased dialysate DA in the shell and core of rats trained to respond for sucrose by nose poking as well as in those trained by lever pressing. In rats trained to respond for sucrose by nose poking on a FR5 schedule dialysate DA also increased selectively in the NAc shell during reinforced responding and in both the shell and core under passive sucrose presentation. These findings, while provide an explanation for the discrepancies existing in the literature over the responsiveness of shell and core DA in rats responding for food, are consistent with the notion that NAc shell and core DA encode different aspects of reinforcement. PMID- 26275925 TI - Dopamine-sensitive signaling mediators modulate psychostimulant-induced ultrasonic vocalization behavior in rats. AB - The mesolimbic dopamine system plays a major role in psychostimulant-induced ultrasonic vocalization (USV) behavior in rodents. Within this system, psychostimulants elevate synaptic concentrations of dopamine thereby leading to exaggerated activation of postsynaptic dopamine receptors within the D1-like and D2-like subfamilies. Dopamine receptor stimulation activate several transmembrane signaling systems and cognate intracellular mediators; downstream activation of transcription factors then conveys the information from receptor activation to appropriate modulation of cellular and physiologic functions. We previously showed that cocaine-induced USV behavior was associated with enhanced expression of the neurotrophin BDNF. Like cocaine, amphetamine also increases synaptic dopamine levels, albeit primarily through facilitating dopamine release. Therefore, in the present study we investigated whether amphetamine and cocaine similarly activate dopamine-linked signaling cascades to regulate intracellular mediators leading to induction of USV behavior. The results show that amphetamine increased the emission of 50 kHz USVs and this effect was blocked by SCH23390, a D1 receptor antagonist. Similar to cocaine, amphetamine increased BDNF protein expression in discrete brain regions, while pretreatment with K252a, a trkB neurotrophin receptor inhibitor, significantly reduced amphetamine-induced USV behavior. Inhibition of cyclic-AMP/PKA signaling with H89 or inhibition of PLC signaling with U73122 significantly blocked both the acute and subchronic amphetamine-induced USV behavior. In contrast, pharmacologic inhibition of either pathway enhanced cocaine-induced USV behavior. Although cocaine and amphetamine similarly modulate neurotrophin expression and USV, the molecular mechanisms by which these psychostimulants differentially activate dopamine receptor subtypes or other monoaminergic systems may be responsible for the distinct aspects of behavioral responses. PMID- 26275927 TI - Subcortical modulation in auditory processing and auditory hallucinations. AB - Hearing perception in individuals with auditory hallucinations has not been well studied. Auditory hallucinations have previously been shown to involve primary auditory cortex activation. This activation suggests that auditory hallucinations activate the terminal of the auditory pathway as if auditory signals are submitted from the cochlea, and that a hallucinatory event is therefore perceived as hearing. The primary auditory cortex is stimulated by some unknown source that is outside of the auditory pathway. The current study aimed to assess the outcomes of stimulating the primary auditory cortex through the auditory pathway in individuals who have experienced auditory hallucinations. Sixteen patients with schizophrenia underwent functional magnetic resonance imaging (fMRI) sessions, as well as hallucination assessments. During the fMRI session, auditory stimuli were presented in one-second intervals at times when scanner noise was absent. Participants listened to auditory stimuli of sine waves (SW) (4-5.5kHz), English words (EW), and acoustically reversed English words (arEW) in a block design fashion. The arEW were employed to deliver the sound of a human voice with minimal linguistic components. Patients' auditory hallucination severity was assessed by the auditory hallucination item of the Brief Psychiatric Rating Scale (BPRS). During perception of arEW when compared with perception of SW, bilateral activation of the globus pallidus correlated with severity of auditory hallucinations. EW when compared with arEW did not correlate with auditory hallucination severity. Our findings suggest that the sensitivity of the globus pallidus to the human voice is associated with the severity of auditory hallucination. PMID- 26275928 TI - The effect of various model parameters on enamel caries lesions in a dose response model in situ. AB - OBJECTIVES: The aim of this exploratory double-blinded, randomized, cross-over, in situ study was to compare the effects of various model parameters ('intervention', 'brushing', 'position') on enamel caries lesions in a dose response model. METHODS: In each of four experimental legs of four weeks 16 participants wore intraoral mandibular appliances with four 'plaque-retaining' and four 'easily cleanable' positioned pre-demineralized bovine enamel specimens in the vestibular flanges mimicking proximal and buccal surfaces, respectively (n=512). The four randomly allocated interventions (either application only or brushing) included the following dentifrices: AlF3 1360ppmF(-)+chlorhexidine 0.05% (Lacalut aktiv, LA1360), NaF 1,450ppmF(-)(Blend-a-Med ProExpert), NaF 500ppm F(-) and 0ppm F(-) as negative control (NC) (both experimental, based on Blend-a-Med ProExpert). RESULTS: Differences in integrated mineral loss (DeltaDeltaZ) and lesion depth (DeltaLD) were calculated between values before and after the in situ period using transversal microradiography. Significant differences for DeltaDeltaZ [adjusted mean (95% CI))] were found between NC, NaF500 and LA1360for both 'plaque-retaining' [-1830 (-2371;1289); -986 ( 1530;442); -2 (-548;544)vol%*MUm] as well as 'easily cleanable' specimens [-399 ( 682; -116); -391 (-672; -110); -16 (-302;270)vol%*MUm]. Values for NaF1450 revealed a similar dose-response as LA1360.Values for LA1360 and NaF1450 did not differ significantly (p>0.05; ANCOVA). CONCLUSION/CLINICAL SIGNIFICANCE: The design of the present in situ study was able to reveal a fluoride dose-response to hamper further demineralization of enamel specimens for 'easily cleanable' and 'plaque-retaining' sites being brushed or not. Particularly 'plaque-retaining' sites seem to be recommendable for measuring potential anticaries efficacy in situ. PMID- 26275929 TI - Clinical efficacy of a bleaching enzyme-based toothpaste. A double-blind controlled clinical trial. AB - OBJECTIVES: To assess the efficacy of a bleaching enzyme-based toothpaste. MATERIAL AND METHODS: A randomized clinical trial was carried out, comprising 48 participants with teeth exhibiting color A3 or higher according to the Vita Classical guide. One-half of the sample received the bleaching enzyme-based toothpaste (White Kin((r))), while the other received placebo toothpaste. Both products were supplied in identical containers and had the same composition except for the active components. The teeth color was measured with a spectrophotometer. The patients were instructed to brush their teeth three times a day during 3 min with the assigned product, during 12 weeks. The color measurements were repeated after 3, 6, 9 and 12 weeks of treatment. Color variation was based on the CIE L*a*b* coordinates, DeltaE and the EW index. The relationship of these variables at different observation times were performed using a generalized estimating equations model, which evaluated the effect of treatment, time and interaction. RESULTS: The patients using the bleaching enzyme based toothpaste showed an increase in lightness (80.14 -treatment- versus 79.25 control group-) and a reduction in component b*. DeltaE was found higher in the treatment group (p=0.064), close to statistical significance. CONCLUSIONS: The bleaching enzyme-based toothpaste could be potentially efficient in the modification in tooth color progressing from the third to ninth week of treatment, tending to stabilize after the ninth week. CLINICAL RELEVANCE: A very low carbamide peroxide concentration, with the incorporation of lactoperoxidase, tooth paste, tends to offer clinically satisfactory results, in terms of modifications in tooth color, nevertheless no significant differences were founded when compared to the control group, with an oral hygiene controlled along the study. PMID- 26275930 TI - Optimal choice of footwear in the elderly population. AB - To discover whether changes in foot morphology and pain tolerance may favor the use of inadequate footwear in old age. 100 participants, mean age 81.60 +/- 8.26 years attended an outpatient clinic where self-reported demographic data, frequency checked their feet, measurements of foot sensitivity, foot size and shoe size. Only 19% checked their feet every day, 73% revealed symptoms of neuropathy and 83% used inadequate footwear on at least one foot. In a bivariate analysis, no significant differences were observed. Distinct physical changes affect the feet in the elderly population. Decreased sensitivity and absence of regular foot checks can contribute to use of inadequate footwear. Often, it is necessary to use a different shoe size to ensure that the footwear matches the actual dimensions and true needs of each foot in order to improve functionality and prevent the onset of severe medical conditions and/or foot deformities. PMID- 26275931 TI - Effect of graphene oxide on the conformational transitions of amyloid beta peptide: A molecular dynamics simulation study. AB - The interactions between nanomaterials (NMs) and amyloid proteins are central to the nanotechnology-based diagnostics and therapy in neurodegenerative disorders such as Alzheimer's and Parkinson's. Graphene oxide (GO) and its derivatives have shown to modulate the aggregation pattern of disease causing amyloid beta (Abeta) peptide. However, the mechanism is still not well understood. Using molecular dynamics simulations, the effect of graphene oxide (GO) and reduced graphene oxide (rGO) having carbon:oxygen ratio of 4:1 and 10:1, respectively, on the conformational transitions (alpha-helix to beta-sheet) and the dynamics of the peptide was investigated. GO and rGO decreased the beta-strand propensity of amino acid residues in Abeta. The peptide displayed different modes of adsorption on GO and rGO. The adsorption on GO was dominated by electrostatic interactions, whereas on rGO, both van der Waals and electrostatic interactions contributed in the adsorption of the peptide. Our study revealed that the slight increase in the hydrophobic patches on rGO made it more effective inhibitor of conformational transitions in the peptide. Alpha helix-beta sheet transition in Abeta peptide could be one of the plausible mechanism by which graphene oxide may inhibit amyloid fibrillation. PMID- 26275932 TI - Fish oil and flax seed oil supplemented diets increase FFAR4 expression in the rat colon. AB - BACKGROUND AND OBJECTIVE: Omega-3 fatty acids, such as alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are polyunsaturated fatty acids (PUFA) that have long been associated with anti inflammatory activity and general benefit toward human health. Over the last decade, the identification of a family of cell-surface G protein-coupled receptors that bind and are activated by free-fatty acids, including omega-3 fatty acids, suggest that many effects of PUFA are receptor-mediated. One such receptor, free-fatty acid receptor-4 (FFAR4), previously described as GPR120, has been shown to modulate anti-inflammatory and insulin-sensitizing effects in response to PUFA such as ALA and DHA. Additionally, FFAR4 stimulates secretion of the insulin secretagogue glucagon-like peptide-1 (GLP-1) from the GI tract and acts as a dietary sensor to regulate energy availability. The aim of the current study was to assess the effects of dietary omega-3 fatty acid supplementation on FFAR4 expression in the rat colon. METHODS: Sprague-Dawley rats were fed control soybean oil diets or alternatively, diets supplemented with either fish oil, which is enriched in DHA and EPA, or flaxseed oil, which is enriched in ALA, for 7 weeks. GLP-1 and blood glucose levels were monitored weekly and at the end of the study period, expression of FFAR4 and the inflammatory marker TNF-alpha was assessed. RESULTS: Our findings indicate that GLP-1 and blood glucose levels were unaffected by omega-3 fatty acid supplementation, however, animals that were fed fish or flaxseed oil-supplemented diets had significantly heightened colonic FFAR4 and actin expression, and reduced expression of the pro-inflammatory cytokine TNF-alpha compared to animals fed control diets. CONCLUSIONS: These results suggest that similar to ingestion of other fats, dietary-intake of omega 3 fatty acids can alter FFAR4 expression within the colon. PMID- 26275933 TI - Can adaptive threshold-based metabolic tumor volume (MTV) and lean body mass corrected standard uptake value (SUL) predict prognosis in head and neck cancer patients treated with definitive radiotherapy/chemoradiotherapy? AB - PURPOSE: To evaluate the predictive value of adaptive threshold-based metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax) and maximum lean body mass corrected SUV (SULmax) measured on pretreatment positron emission tomography and computed tomography (PET/CT) imaging in head and neck cancer patients treated with definitive radiotherapy/chemoradiotherapy. MATERIALS AND METHODS: Pretreatment PET/CT of the 62 patients with locally advanced head and neck cancer who were treated consecutively between May 2010 and February 2013 were reviewed retrospectively. The maximum FDG uptake of the primary tumor was defined according to SUVmax and SULmax. Multiple threshold levels between 60% and 10% of the SUVmax and SULmax were tested with intervals of 5% to 10% in order to define the most suitable threshold value for the metabolic activity of each patient's tumor (adaptive threshold). MTV was calculated according to this value. We evaluated the relationship of mean values of MTV, SUVmax and SULmax with treatment response, local recurrence, distant metastasis and disease-related death. Receiver-operating characteristic (ROC) curve analysis was done to obtain optimal predictive cut-off values for MTV and SULmax which were found to have a predictive value. Local recurrence-free (LRFS), disease-free (DFS) and overall survival (OS) were examined according to these cut-offs. RESULTS: Forty six patients had complete response, 15 had partial response, and 1 had stable disease 6 weeks after the completion of treatment. Median follow-up of the entire cohort was 18 months. Of 46 complete responders 10 had local recurrence, and of 16 partial or no responders 10 had local progression. Eighteen patients died. Adaptive threshold-based MTV had significant predictive value for treatment response (p=0.011), local recurrence/progression (p=0.050), and disease-related death (p=0.024). SULmax had a predictive value for local recurrence/progression (p=0.030). ROC curves analysis revealed a cut-off value of 14.00 mL for MTV and 10.15 for SULmax. Three-year LRFS and DFS rates were significantly lower in patients with MTV >= 14.00 mL (p=0.026, p=0.018 respectively), and SULmax>=10.15 (p=0.017, p=0.022 respectively). SULmax did not have a significant predictive value for OS whereas MTV had (p=0.025). CONCLUSION: Adaptive threshold-based MTV and SULmax could have a role in predicting local control and survival in head and neck cancer patients. PMID- 26275934 TI - Predicting urban design effects on physical activity and public health: A case study. AB - With increasing global concerns about obesity and related health effects, tools to predict how urban form affects population physical activity and health are needed. However, such tools have not been well established. This article develops a computer simulation model for forecasting the health effects of urban features that promote walking. The article demonstrates the model using a proposed small area plan for a neighborhood of 10,400 residents in Raleigh, North Carolina, one of the fastest-growing and most sprawling U.S. cities. The simulation model predicts that the plan would increase average daily time spent walking for transportation by 17 min. As a result, annual deaths from all causes are predicted to decrease by 5.5%. Annual new cases of diabetes, coronary heart disease, stroke, and hypertension are predicted to decline by 1.9%, 2.3%, 1.3%, and 1.6%, respectively. The present value of these health benefits is $21,000 per resident. PMID- 26275936 TI - Molecular cloning, characterization and expression of Lc-Sox11a in large yellow croaker Larimichthys crocea. AB - Sox genes play important roles in various developmental processes such as sex determination, embryogenesis, oogenesis, neurogenesis, and larval development. In order to clarify the roles of Sox genes in the developmental process of large yellow croaker, the full-length cDNA of the Sox11a gene (Lc-Sox11a) was cloned for the first time. Bioinformatics analysis indicated that Lc-Sox11a contains a protein of 366 amino acids with a Ser-rich region, a C-terminal conserved region, and a high mobility group box. The expression of Lc-Sox11a in different tissues of both sexes and in different developmental embryonic stages revealed that Lc Sox11a were expressed with tissue and gender specificity, of which the expression level in female was ovary>brain>eye>gill; in male was brain>testis>gill. The gender differences occurred in the brain and eye with the male brain>female brain, female eye>male eye. Moreover, the expression of Lc-Sox11a in the gonad and brain at different growth stages was detected. Significant up-regulated expression of Lc-Sox11a was found in the ovary and the male brain at 1000dph (days post hatching) compared with 270dph and 635dph. However, significant down regulated expression of Lc-Sox11a occurred in the testis with growth. Besides, the expression of Lc-Sox11a in the female brain showed a trend of first rising then falling, with the highest peak in 635dph. The results of in situ hybridization displayed that Lc-Sox11a was widely distributed only in cytoplasm of oocytes at each stage in oogenesis. In early stage of oocytes, Lc-Sox11a was expressed weakly and evenly. As the appearance of vacuoles and synthesis of yolks, positive signals of Lc-Sox11a distributed intensively in the residual cytoplasm. In spermatogenesis, Lc-Sox11a was distributed in cytoplasm of all male germ cells except spermatozoon with spermatogonium>spermatocyte>spermatid. During embryogenesis, Lc-Sox11a was expressed in most embryonic stages, the highest expression occurred in the formation-of-eye-lens stage, closely followed by the closure-of-blastopore stage, then the beginning-of-heart-pulsation stage. The results of whole mount in situ hybridization showed that the expression of Lc Sox11a began to increase beginning with the multiple-cell stage, with the major distribution of Lc-Sox11a in the brain and eye areas in the pre-hatching stage. PMID- 26275937 TI - A high-density SSR genetic map constructed from a F2 population of Gossypium hirsutum and Gossypium darwinii. AB - The cultivated allotetraploid species Gossypium hirsutum, accounts for 90% of the world cotton production, has narrow genetic basis that's why its yield, quality or stress resistance breeding is stagnant. It is therefore, essential to explore desirable genes from Gossypium darwinii which has enviable traits such as high fiber fineness, drought tolerance, fusarium and verticillium resistance. We used G. darwinii as primary plant materials in this study not only to enrich the genetic diversity of exiting germplasm but also to better understand its genome structure. An interspecific high density linkage map of allotetraploid cotton was constructed using F2 population (G. hirsutum*G. darwinii). The map was based entirely on genome-wide simple sequence repeat (SSR) markers. A total of 2763 markers were mapped in 26 linkage groups (chromosomes) covering a genome length of 4176.7cM with an average inter-locus distance of 1.5cM. The length of the chromosomes ranged from 84.7 to 238.5cM with an average length of 160.6cM. At subgenome length was 2160.7cM with an average distance of 1.6cM, where as Dt genome length was 2016cM with an average distance of 1.4cM. There were 601 distorted SSR loci. Less number of segregation distortion loci were located in At subgenome than in Dt subgenome. Two post-polyploidization reciprocal translocations of "A2/A3 and A4/A5" were suggested by 44 pairs of duplicate loci. PMID- 26275938 TI - Characterization of vasa in the gonads of different ploidy fish. AB - Vasa is an essential gene for germ cell development belonging to the DEAD-box family. In this study, we comparatively analyzed the expression characteristics of vasa in diploids, triploids, and tetraploids. The sequences showed high similarity among these fish and other vertebrates, with characteristic domains. Tissue expression analysis revealed that vasa was expressed exclusively in the gonad of different ploidy fishes. During embryogenesis, vasa expression was lower in diploid than in triploid and tetraploid fish, caused by doubling of the genome of tetraploids and abnormal gonads in the triploid fish. In adults, vasa mRNA levels were significantly lower in the testes of sterile triploid fish compared with fertile diploids and tetraploids. In the ovaries, triploid fish showed consistently high expression from the non-breeding season to the breeding season. Immunohistochemistry and western blotting results also supported the abnormal expression of vasa in triploid gonads. This study demonstrates, for the first time, that fish of different ploidy exhibit different expression patterns of vasa that contribute to the differentiation of gonadal development. PMID- 26275935 TI - Memory trace replay: the shaping of memory consolidation by neuromodulation. AB - The consolidation of memories for places and events is thought to rely, at the network level, on the replay of spatially tuned neuronal firing patterns representing discrete places and spatial trajectories. This occurs in the hippocampal-entorhinal circuit during sharp wave ripple events (SWRs) that occur during sleep or rest. Here, we review theoretical models of lingering place cell excitability and behaviorally induced synaptic plasticity within cell assemblies to explain which sequences or places are replayed. We further provide new insights into how fluctuations in cholinergic tone during different behavioral states might shape the direction of replay and how dopaminergic release in response to novelty or reward can modulate which cell assemblies are replayed. PMID- 26275939 TI - Molecular and clinical characterization of Waardenburg syndrome type I in an Iranian cohort with two novel PAX3 mutations. AB - Waardenburg syndrome (WS) is a disease of abnormal neural-crest derived melanocyte development characterized by hearing loss and pigmentary disturbances in hair, eyes and skin. WS is subdivided into four major types, WS1-WS4, where WS1 is recognized by the presence of dystopia canthorum, with PAX3 being the only known gene involved. This study aimed at investigating PAX3 mutations and clinical characteristics of WS1 in a group of Iranian patients. A total of 12 WS1 patients from four unrelated Iranian families were enrolled. Waardenburg consortium guidelines were used for WS1 diagnosis. A detailed family history was traced and a thorough clinical examination was performed for all participants. Furthermore, WS1 patients underwent screening for PAX3 mutations using PCR sequencing. Dystopia canthorum, broad high nasal root and synophrys were observed in all patients. Early graying, hair discoloration, hypoplastic blue eyes (characteristic brilliant blue iris) and hearing loss were the most common features observed, while heterochromia iridis was the least frequently observed sign among the studied Iranian WS1 patients. Genetic analysis of PAX3 revealed four mutations including c.667C>T, c.784C>T, c.951delT and c.451+3A>C. Two of the four mutations reported here (c.951delT and c.451+3A>C) are being reported for the first time in this study. Our data provide insight into genotypic and phenotypic spectrum of WS1 in an Iranian series of patients. Our results expand the spectrum of PAX3 mutations and may have implications for the genetic counseling of WS in Iran. PMID- 26275940 TI - A combined evidence Bayesian method for human ancestry inference applied to Afro Colombians. AB - Uniparental genetic markers, mitochondrial DNA (mtDNA) and Y chromosomal DNA, are widely used for the inference of human ancestry. However, the resolution of ancestral origins based on mtDNA haplotypes is limited by the fact that such haplotypes are often found to be distributed across wide geographical regions. We have addressed this issue here by combining two sources of ancestry information that have typically been considered separately: historical records regarding population origins and genetic information on mtDNA haplotypes. To combine these distinct data sources, we applied a Bayesian approach that considers historical records, in the form of prior probabilities, together with data on the geographical distribution of mtDNA haplotypes, formulated as likelihoods, to yield ancestry assignments from posterior probabilities. This combined evidence Bayesian approach to ancestry assignment was evaluated for its ability to accurately assign sub-continental African ancestral origins to Afro-Colombians based on their mtDNA haplotypes. We demonstrate that the incorporation of historical prior probabilities via this analytical framework can provide for substantially increased resolution in sub-continental African ancestry assignment for members of this population. In addition, a personalized approach to ancestry assignment that involves the tuning of priors to individual mtDNA haplotypes yields even greater resolution for individual ancestry assignment. Despite the fact that Colombia has a large population of Afro-descendants, the ancestry of this community has been understudied relative to populations with primarily European and Native American ancestry. Thus, the application of the kind of combined evidence approach developed here to the study of ancestry in the Afro Colombian population has the potential to be impactful. The formal Bayesian analytical framework we propose for combining historical and genetic information also has the potential to be widely applied across various global populations and for different genetic markers. PMID- 26275941 TI - The allergenic protein Tha p 2 of processionary moths of the genus Thaumetopoea (Thaumetopoeinae, Notodontidae, Lepidoptera): Characterization and evolution. AB - The allergenic Tha p 2 protein has been extracted recently from the urticating setae of the pine processionary moth Thaumetopoea pityocampa. In the present paper, we test for the occurrence of this protein in other Thaumetopoeinae, with a particular focus on members of the genus Thaumetopoea, as well as unrelated moth species, to better understand the physicochemical properties of the protein, the nature of encoding genes and their evolutionary history. Tha p 2 is encoded by the intronless gene Tha p 2 that is restricted to the processionary moths (Thaumetopoeinae, Notodontidae, Lepidoptera). Most of the species present two isoforms of Tha p 2 that can be interpreted as the result of heterozygosity in the single gene. The only exception is represented by Thaumetopoea wilkinsoni, in which 20 different isoforms occur in a single specimen, leading to the conclusion that, at least in this species, multiple copies of Tha p 2 exist. Serine, glycine, cysteine and leucine are abundant in Tha p 2, a protein well conserved among processionary moths. The predicted secondary structures of Tha p 2 indicate the presence of 3 alpha-helices and six beta-barrels. Finally, the evolution of the gene and the protein was characterized by a combination of positive and negative selection, with the latter being more evident. PMID- 26275942 TI - Convergent evolution of SOCS4 between yak and Tibetan antelope in response to high-altitude stress. AB - Convergence often occurs when organisms with different ancestors adopt similar adaptations to environmental stresses. Convergent (sometimes called parallel) evolution at the genetic level is now known to be more common than previously suspected. Studying convergent evolution at the molecular level makes it possible to gain a better understanding of the common mechanisms deployed by different species. Yak (Bos grunniens) and Tibetan antelope (Pantholops hodgsonii), which are endemic to the Qinghai-Tibetan Plateau, both have numerous traits that are adaptive to high altitudes. However, it is still unclear whether these two species have undergone adaptive convergence at the genetic level. We used genomic data to detect possible examples of convergent evolution between yak and Tibetan antelope. We found that one gene, SOCS4, which is involved in the regulation of HIF-1alpha, showed a signature of convergent evolution. Our results have provided clues that may be important for understanding high-altitude adaptations in animals. PMID- 26275943 TI - Genetic polymorphisms of the AMPD1 gene and their correlations with IMP contents in Fast Partridge and Lingshan chickens. AB - The object of this study was to evaluate associations between the adenosine monophosphate deaminase 1 (AMPD1) gene polymorphisms and inosine monophosphate acid (IMP) contents of chicken to provide a molecular marker for breeding. Three single nucleotide polymorphisms (SNPs), g.4064G/A, g.5573A/G and g.6805G/A were detected in exons IV, VI, and VIII of the AMPD1 gene in Fast Partridge and Lingshan chickens, respectively. All were purine conversion and caused no alteration in amino acid sequence. Statistical analysis revealed that Lingshan chicken with the homozygous genotype AA at position 4064 and 6805 had a significantly greater IMP content than those with the GG genotype (P<0.05). Fast Partridge chicken with the genotype GG at position 6805 had a significantly greater IMP content compared with those with the AA genotype (P<0.05). In conclusion, the polymorphism at g.6805A/G was correlated with IMP content (P<0.05) in both Fast Partridge and Lingshan chickens. The results in our study suggest that SNP 6805A/G can be used as a possible candidate marker of IMP content of chicken. PMID- 26275944 TI - MiR-205 promotes motility of ovarian cancer cells via targeting ZEB1. AB - AIM: To investigate the clinical significance of microRNA-205 (miR-205) and zinc finger E-box binding homeobox 1 (ZEB1) in epithelial ovarian cancer (EOC) and the underlying mechanisms by which they are involved into tumorigenesis. METHODS: Expression levels of miR-205 and ZEB1 mRNA in EOC tissues were detected by quantitative real-time PCR. Their associations with clinicopathological features of EOC patients were statistically analyzed. Luciferase reporter assay was used to confirm target associations between miR-205 and ZEB1. After that, the functions of miR-205-ZEB1 axis on cell migration and invasion were further determined by transwell assay in vitro. RESULTS: Expression levels of miR-205 (P=0.0001) and ZEB1 mRNA (P<0.0001) in clinical EOC tissues were significantly higher and lower than those in normal tissues, respectively. Interestingly, there was a negative correlation between miR-205 and ZEB1 mRNA expression in EOC tissues (P=0.01). Additionally, miR-205-upregulation and/or ZEB1-downregulation were significantly associated with high pathological grade and advanced clinical stage of EOC patients (all P<0.05). Meantime, luciferase reporter assays identified ZEB1 as a direct target of miR-205 in EOC cells. Moreover, miR-205 blockage inhibited, whereas miR-205 mimics promoted the motility of EOC cells in vitro. Importantly, all the alterations of the above cellular phenotypes by blocking or enhancing of miR-205 could be alleviated by subsequent suppression or re-introduction of its target ZEB1, respectively. CONCLUSION: MiR-205, acting as an oncogenic miRNA, may promote the clinical progression of EOC patients and enhance the cellular motility in vitro by directly and negatively regulating ZEB1, providing a potential therapeutic strategy for suppression of EOC metastasis. PMID- 26275946 TI - Expression and hormonal regulation of membrane progesterone receptors in human astrocytoma cells. AB - Progesterone (P) participates in the regulation of the growth of several tumors, including astrocytomas, the most common and malignant human brain tumors. It has been reported that P induces astrocytomas growth in part by its interaction with its intracellular receptors (PR). Recently, it has been reported that membrane progesterone receptors (mPRs) are expressed in ovarian and breast cancer cells, and that P could exert some actions through these receptors, however, it is unknown whether mPRs are expressed in astrocytomas. In this work, U251 and U87 cell lines derived from human astrocytomas grade IV were used to study the expression, localization and hormonal regulation of three mPRs subtypes. Using RT qPCR and Western blot techniques, we found that mPRalpha and mPRbeta are clearly expressed at mRNA and protein levels in astrocytoma cells whereas mPRgamma was barely expressed in these cells. Immunofluorescence staining showed that mPRalpha and mPRbeta were mainly located in the cell surface. Flow cytometry assays demonstrated that in U251 and U87 cells, mPRbeta is expressed by a higher percentage of both permeabilized and non-permeabilized cells as compared with mPRalpha. The percentage of cells expressing mPRgamma was very low. P and estradiol (E) (10, 100 nM and 1 MUM) decreased mPRalpha protein content at 12 h. In contrast, both P (100 nM and 1 MUM) and E (10 and 100 nM) increased mPRbeta content. Finally, by in silico analysis, we identified that mPRalpha, mPRbeta and mPRgamma promoters contain several progesterone and estrogen response elements. Our results indicate that mPRs are expressed in human astrocytoma cells, exhibiting a differential regulation by E and P. These data suggest that some P actions in astrocytoma cells may be mediated by mPRs. PMID- 26275945 TI - Relative importance of summer sun exposure, vitamin D intake, and genes to vitamin D status in Dutch older adults: The B-PROOF study. AB - BACKGROUND/OBJECTIVES: The prevalence of vitamin D deficiency among seniors is high. Whereas sun exposure, vitamin D intake, genes, demographics, and lifestyle have been identified as being important determinants of vitamin D status, the impact of these factors is expected to differ across populations. To improve current prevention and treatment strategies, this study aimed to explore the main determinants of vitamin D status and its relative importance in a population of community-dwelling Dutch older adults. METHODS/SUBJECTS: Serum 25-hydroxyvitamin D (25(OH)D) was measured in 2857 adults aged >=65 years. Sun exposure was assessed with a structured questionnaire (n=1012), vitamin D intake using a Food Frequency Questionnaire (n=596), and data on genetic variation that may affect 25(OH)D status was obtained for 4 genes, DHCR7 (rs12785878), CYP2R1 (rs10741657), GC (rs2282679), and CYP24A1 (rs6013897) (n=2530). RESULTS: Serum 25(OH)D concentrations <50nmol/L were observed in 45% of the population; only 6% of these participants used vitamin D supplements. Sun exposure (being outside daily during summer: 66+/-25nmol/L vs not being outside daily during summer: 58+/-27nmol/L, P=0.02) and vitamin D intake (per unit MUg/day during winter/spring: 3.1+/ 0.75nmol/L, P<0.0001) were associated with higher 25(OH)D concentrations. Major allele carriers of SNPs related to DHCR7, CYP24A1, and GC, as well as CYP2R1 minor allele carriers had the highest 25(OH)D concentrations. Together, sun (R2=0.29), vitamin D intake (R2=0.24), and genes (R2=0.28) explained 35% (R2=0.35) of the variation in 25(OH)D concentrations during summer/autumn period, when adjusted for age, sex, BMI, education, alcohol consumption, smoking, physical activity, and self-rated health status (n=185). CONCLUSION: The investigated determinants explained 35% of 25(OH)D status. Of the three main determinants under study, sun exposure still appeared to be an important determinant of serum 25(OH)D in older individuals, closely followed by genes, and vitamin D intake. Given the low frequency of vitamin D supplement use in this population, promoting supplement use may be an inexpensive, easy, and effective strategy to fight vitamin D deficiency. PMID- 26275948 TI - Decay data of radionuclides along the valley of nuclear stability for astrophysical applications. AB - Several directions of the demand for decay data in nuclear astrophysics are discussed for radionuclides near the valley of nuclear stability. The current half-life and gamma-ray intensity evaluation results are presented for some radionuclides of astrophysical interest. An extended list of such nuclides is offered for their nuclear characteristics to be further evaluated by the Decay Data Evaluation Project collaboration participants. PMID- 26275947 TI - ALPK1 affects testosterone mediated regulation of proinflammatory cytokines production. AB - Alpha-protein kinase 1, also known as alpha-kinase 1 (ALPK1), is associated with chronic kidney disease (CKD), myocardial infarction, gout and type 2 diabetes mellitus (DM). In addition to having an inductive effect on the proinflammatory cytokines in monocytic THP1 cells, ALPK1 is expressed abundantly in the mouse testes. Low testosterone levels are commonly associated with arthritis, CKD, type 2 DM, cardiovascular disease and inflammation. The testosterone's anti inflammatory effect has been demonstrated to reduce proinflammatory cytokines and adhesion molecules. In this study, we found that ALPK1 transgenic mice showed lower levels of testosterone in both the testes and the serum. Decreasing endogenous ALPK1 enhanced testosterone levels and transcripts of testosterone regulated genes (P450scc, 3beta-HSD, P450C17, 17beta-HSD, StAR, and INSL3) in TM3 Leydig cells. In contrast, increasing testosterone decreased ALPK1 in both TM3 and monocytic THP1 cells. This decrease was accompanied by a reduction of the proinflammatory cytokines. Increased ALPK1 levels attenuated the testosterone effects in THP1 cells. Finally, we also found that ALPK1 increased the release of TNF-alpha and TGF-beta1 in the human embryonic kidney 293 cells, while testosterone inhibited ALPK1 in the primary kidney cells. Taken together, this data suggests that the balance between ALPK1 and testosterone plays a critical role in the testosterone-mediated inhibition of proinflammatory cytokines. PMID- 26275950 TI - CCR 20th Anniversary Commentary: Divide and Conquer-Breast Cancer Subtypes and Response to Therapy. AB - The article by Rouzier and colleagues, published in the August 15, 2005, issue of Clinical Cancer Research, demonstrated that different molecular subtypes of breast cancer have different degrees of sensitivity to chemotherapy, but the extent of response to neoadjuvant therapy has a different meaning by subtype. Several molecular subtype-specific clinical trials are under way to maximize pathologic complete response rates in triple-negative breast cancer and HER2 positive cancers, and to provide adjuvant treatment options for patients with residual invasive disease. See related article by Rouzier et al., Clin Cancer Res 2005;11(16) Aug 15, 2005;5678-85. PMID- 26275951 TI - CCR 20th Anniversary Commentary: RAS as a Biomarker for EGFR--Targeted Therapy for Colorectal Cancer-From Concept to Practice. AB - Clinical data support the use of EGFR mAbs in patients with metastatic colorectal cancer (mCRC) with wild-type RAS status. This notion, hypothesized in the review article by Camp, Ellis, and colleagues in the January 1, 2005, issue of Clinical Cancer Research, serves as an example of the successful application of basic science principles to clinical practice. The exclusion of patients with mCRC with Ras-mutated tumors from therapy with EGFR mAbs has led to improved outcomes while sparing patients unnecessary and potentially harmful therapy. See related article by Camp et al., Clin Cancer Res 2005;11(1): January 1, 2005;397-405. PMID- 26275952 TI - FDA Approval: Ibrutinib for Patients with Previously Treated Mantle Cell Lymphoma and Previously Treated Chronic Lymphocytic Leukemia. AB - On November 13, 2013, the FDA granted accelerated approval to ibrutinib (IMBRUVICA capsules; Pharmacyclics, Inc.) for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. On February 12, 2014, the FDA granted accelerated approval for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy. Ibrutinib is a first-in-class Bruton's tyrosine kinase (BTK) inhibitor that received all four expedited programs of the FDA: Fast-Track designation, Breakthrough Therapy designation, Priority Review, and Accelerated Approval. Both approvals were based on overall response rate (ORR) and duration of response (DOR) in single-arm clinical trials in patients with prior treatment. In MCL (N = 111), the complete and partial response rates were 17.1% and 48.6%, respectively, for an ORR of 65.8% [95% confidence interval (CI), 56.2%-74.5%]. The median DOR was 17.5 months (95% CI, 15.8-not reached). In CLL (N = 48), the ORR was 58.3% (95% CI, 43.2%-72.4%), and the DOR ranged from 5.6 to 24.2 months. The most common adverse reactions (>= 30% in either trial) were thrombocytopenia, diarrhea, neutropenia, bruising, upper respiratory tract infection, anemia, fatigue, musculoskeletal pain, peripheral edema, and nausea. PMID- 26275953 TI - Effects of BRCA1/2 on Ovarian and Breast Cancer Survival--Letter. PMID- 26275954 TI - Effects of BRCA1/2 on Ovarian and Breast Cancer Survival--Response. PMID- 26275955 TI - Diffusion-Weighted MRI for Lymphoma Restaging--Letter. PMID- 26275956 TI - Diffusion-Weighted MRI for Lymphoma Restaging--Response. PMID- 26275957 TI - Dimethyl sulfoxide-caused changes in pro- and anti-angiogenic factor levels could contribute to an anti-angiogenic response in HeLa cells. AB - Dimethyl sulfoxide (DMSO) is widely used in biological research as a general solvent. While it has been previously demonstrated that DMSO possesses a wide range of pharmacological effects, there is no published work regarding the effects of DMSO on pro-angiogenic factor levels. This study was designed to investigate the possible effects of DMSO on the levels of three pro-angiogenic factors released from HeLa cells in vitro. Cells were treated with two different and previously determined concentrations of DMSO. The cytotoxic effects of DMSO concentrations on HeLa cells were determined via MTT. Survival rates of DMSO treated cells were determined by Invitrogen live/dead viability/cytotoxicity kit and trypan blue exclusion assay. Changes in the pro-angiogenic levels in media were evaluated by Cayman's Substance P Enzyme Immunoassay ELISA kit. Vascular endothelial growth factor ELISA kit and interferon gamma ELISA kit for substance P, VEGF and IFNgamma respectively. Changes in substance P levels were corrected by standard western blotting. Changes in VEGF and IFNgamma levels were corrected both by western blot and real time PCR. Treatment with 1.4 MUM DMSO caused a time dependent inhibition of cell proliferation at 24, 48 and 72 h. 1.4 MUM DMSO caused a significant reduction in VEGF levels at 72 h of incubation and sharp increases in IFNgamma levels at both 48 and 72 h of incubation. According to real time PCR analyses, DMSO (1.4 MUM) exhibited an inhibitory effect on VEGF but acted as an augmenter of IFNgamma release on HeLa cells in vitro. This is the first report showing that the general solvent DMSO suppressed HeLa cell proliferation, decreased the levels of two pro-angiogenic factors (substance P and VEGF) and increased the release of an anti-angiogenic factor IFNgamma in vitro. PMID- 26275958 TI - Human urinary/seminal phthalates or their metabolite levels and semen quality: A meta-analysis. AB - Health concerns surrounding human exposure to phthalates include diminished semen quality. Epidemiological findings remain inconsistent. We have performed a quality appraisal and meta-analysis to quantitatively summarize evidence for associations between phthalate exposures and human semen quality. Pubmed and Web of Science were searched for pertinent studies through October 2014. Cited references were reviewed to identify secondary studies. Studies that reported quantitative estimates of the association between phthalates or their metabolite levels in humans and semen quality were eligible. Random effects models were used to calculate pooled effects estimates. Overall, 20 studies met our inclusion criteria. Subsequently, 14 studies were included in the meta-analysis. Urinary monobutyl phthalate (MBP) and monobenzyl phthalate (MBzP) were associated with reduced sperm concentration (MBP [7.4-25.3 ug/L], pooled odds ratio [OR]=2.60, 95% confidence interval [CI]=1.32-5.15; MBzP [14.0-540.2 ug/L], pooled OR=2.23, 95% CI=1.16-4.30). Both MBP (24.6-14,459.0 ug/L) and MEHP (3.1-208.1 ug/L) were inversely associated with straight line velocity (VSL; MBP, pooled beta=-2.51, 95% CI=-4.44, -0.59; MEHP, pooled beta=-1.06, 95% CI=-1.99, -0.12). An IQR increase in MBzP and MEP levels (MBzP, IQR=11.35 ug/L; MEP, IQR=449.4 ug/L) was associated with an increase in comet extent (CE; MBzP, pooled beta=3.57, 95% CI=0.89-6.25; MEP, pooled beta=4.22, 95% CI=1.66-6.77). No associations were observed between monomethyl phthalate and any semen parameters. Our meta-analysis strengthens the evidence that specific phthalates or their metabolite levels may affect semen quality. PMID- 26275959 TI - Exploring the interactions between bacteriophage-encoded glycan binding proteins and carbohydrates. AB - There is an unprecedented interest in glycobiology due to the increasing appreciation of its impact on all aspects of life. Likewise, bacteriophage biology is enjoying a new renaissance as the post-antibiotic era fuels the search for novel ways to control harmful bacteria. Phages have spent the last 3 billion years developing ways of recognizing and manipulating bacterial surface glycans. Therefore, phages comprise a massive reservoir of glycan-binding and -hydrolyzing proteins with the potential to be exploited for glycan analysis, bacterial diagnostics and therapeutics. We discuss phage tail proteins that recognize bacterial surface polysaccharides, endolysins that bind and cleave peptidoglycan, Ig-like proteins that attach to mucin glycans, and phage effector proteins that recognize both bacterial and eukaryotic oligosaccharides. PMID- 26275960 TI - Prevalence and Secular Trends in Obesity Among Chinese Adults, 1991-2011. AB - INTRODUCTION: The prevalence of obesity in Chinese adults increased from 1991 to 2000; however, recent changes in this trend are unclear. This study aims to estimate the current prevalence of obesity and to assess trends in obesity and BMI distribution in Chinese adults from 1991 through 2011. METHODS: Height and weight measurements of 12,249 Chinese adults from the 2011 China Health and Nutrition Survey were analyzed (in 2013) together with China Health and Nutrition Survey data for 1991-2009. Obesity was defined as BMI>=28.0 kg/m(2) based on the Working Group on Obesity in China criteria. RESULTS: In the 2011 survey, the age adjusted mean BMI was 23.8 (95% CI=23.7, 23.9) for men and 23.4 (95% CI=23.2, 23.5) for women. The age-adjusted prevalence of obesity was 11.3% (95% CI=10.8%, 11.9%) overall, 11.8% (95% CI=10.8%, 12.6%) among men, and 11.0% (95% CI=10.3%, 11.8%) among women. Estimates of age-adjusted obesity prevalence among the Chinese population were significantly lower than those of the U.S. population (all p<0.05). Over the 20-year period, the prevalence of obesity increased from 2.88% to 11.8% among men (age-adjusted annual change in OR=1.08, 95% CI=1.07, 1.09, p<0.001) and from 4.55% to 11.0% among women (OR=1.05, 95% CI=1.05, 1.06, p<0.001). Similar significant findings were observed for both men and women based on WHO recommendations. CONCLUSIONS: The prevalence of obesity among both Chinese men and women increased significantly from 1991 through 2011, particularly among men. PMID- 26275961 TI - Seipin is involved in the regulation of phosphatidic acid metabolism at a subdomain of the nuclear envelope in yeast. AB - Yeast Fld1 and Ldb16 resemble mammalian seipin, implicated in neutral lipid storage. Both proteins form a complex at the endoplasmic reticulum-lipid droplet (LD) interface. Malfunction of this complex either leads to LD clustering or to the generation of supersized LD (SLD) in close vicinity to the nuclear envelope, in response to altered phospholipid (PL) composition. We show that similar to mutants lacking Fld1, deletion of LDB16 leads to abnormal proliferation of a subdomain of the nuclear envelope, which is tightly associated with clustered LD. The human lipin-1 ortholog, the PAH1 encoded phosphatidic acid (PA) phosphatase, and its activator Nem1 are highly enriched at this site. The specific accumulation of PA-binding marker proteins indicates a local enrichment of PA in the fld1 and ldb16 mutants. Furthermore, we demonstrate that clustered LD in fld1 or ldb16 mutants are transformed to SLD if phosphatidylcholine synthesis is compromised by additional deletion of the phosphatidylethanolamine methyltransferase, Cho2. Notably, treatment of wild-type cells with oleate induced a similar LD clustering and nuclear membrane proliferation phenotype as observed in fld1 and ldb16 mutants. These data suggest that the Fld1-Ldb16 complex affects PA homeostasis at an LD-forming subdomain of the nuclear envelope. Lack of Fld1-Ldb16 leads to locally elevated PA levels that induce an abnormal proliferation of nER membrane structures and the clustering of associated LD. We suggest that the formation of SLD is a consequence of locally altered PL metabolism at this site. PMID- 26275962 TI - High condylectomy versus proportional condylectomy: is secondary orthognathic surgery necessary? AB - The objective of this study was to assess the need for secondary orthognathic surgery in patients undergoing two different condylectomy protocols for active unilateral condylar hyperplasia (UCH). A retrospective cohort study evaluated UCH patients treated by condylectomy. Two groups were established: group 1 comprised those who had undergone a high condylectomy (5 mm removed) and group 2 comprised those who had undergone a proportional condylectomy (removing the difference observed between the measurements of the hyperplastic and the healthy side). Data analysis was done with the Levene test and t-test; a P-value of <0.05 indicated a statistically significant relationship. Forty-nine patients, with an average age of 19.83 years, were analyzed; 11 were included in group 1 and 38 in group 2. There was no statistical difference between the two groups with regard to age or sex (P=0.781). An average of 5.81 mm was removed in the high condylectomy group, while an average of 9.28 mm was removed in the proportional condylectomy group; this difference was statistically significant (P=0.042). Comparing the two groups, proportional condylectomy reduced the need for secondary orthognathic surgery (P<0.001). The proportional condylectomy can be used as the sole surgical treatment in cases of UCH, thus avoiding the need for secondary orthognathic surgery. PMID- 26275963 TI - Sperm quality and selected biochemical parameters of seminal fluid in dogs with benign prostatic hyperplasia. AB - Benign prostatic hyperplasia (BPH) in dogs is most commonly associated with age and increasing concentrations of dihydrotesterone, a hormone that stimulates growth and secretion of the prostatic epithelial cells. During this process, the biochemical composition of prostatic secretion changes, which can affect the quality of semen and limit the ability of the sperm to contribute to fertilization. Therefore, the present study was conducted to examine possible correlation between BPH and biological quality of semen. The study was performed in 11 sexually mature dogs of various breeds. Animals were divided into two groups: healthy dogs (Group I; n = 5; mean age 4.32; SEM = 1.28) and dogs with BPH (Group II n = 6; mean age 6.16; SEM = 0.65). Semen and prostate secretions were collected and evaluated in this study. Standard semen examinations were conducted in the ejaculates collected; moreover, the extent of apoptosis and DNA defragmentation was determined. The selected biochemical parameters were determined in the prostate secretion. According to the examination results, there were no significant differences in standard semen parameters between the two groups of dogs. Nevertheless, morphological tests of semen in dogs with BPH demonstrated elevated percentages of primary defects in spermatozoa. A significant increase (P = 0.01) in DNA defragmentation of sperm was found in dogs with BPH. Moreover, changes in the biochemical composition of prostate secretion were demonstrated. In dogs with BPH, pH of prostate secretions was greater (P = 0.03), concentrations of cholesterol increased while concentrations of Zn and Cu decreased. The study findings reveal that BPH does not change semen quality in dogs. PMID- 26275964 TI - The heterogeneity of verbal short-term memory impairment in aphasia. AB - Verbal short-term memory (STM) impairment represents a frequent and long-lasting deficit in aphasia, and it will prevent patients from recovering fully functional language abilities. The aim of this study was to obtain a more precise understanding of the nature of verbal STM impairment in aphasia, by determining whether verbal STM impairment is merely a consequence of underlying language impairment, as suggested by linguistic accounts of verbal STM, or whether verbal STM impairment reflects an additional, specific deficit. We investigated this question by contrasting item-based STM measures, supposed to depend strongly upon language activation, and order-based STM measures, supposed to reflect the operation of specific, serial order maintenance mechanisms, in a sample of patients with single-word processing deficits at the phonological and/or lexical level. A group-level analysis showed robust impairment for both item and serial order STM aspects in the aphasic group relative to an age-matched control group. An analysis of individual profiles revealed an important heterogeneity of verbal STM profiles, with patients presenting either selective item STM deficits, selective order STM deficits, generalized item and serial order STM deficits or no significant STM impairment. Item but not serial order STM impairment correlated with the severity of phonological impairment. These results disconfirm a strong version of the linguistic account of verbal STM impairment in aphasia, by showing variable impairment to both item and serial order processing aspects of verbal STM. PMID- 26275965 TI - The multisensory function of the human primary visual cortex. AB - It has been nearly 10 years since Ghazanfar and Schroeder (2006) proposed that the neocortex is essentially multisensory in nature. However, it is only recently that sufficient and hard evidence that supports this proposal has accrued. We review evidence that activity within the human primary visual cortex plays an active role in multisensory processes and directly impacts behavioural outcome. This evidence emerges from a full pallet of human brain imaging and brain mapping methods with which multisensory processes are quantitatively assessed by taking advantage of particular strengths of each technique as well as advances in signal analyses. Several general conclusions about multisensory processes in primary visual cortex of humans are supported relatively solidly. First, haemodynamic methods (fMRI/PET) show that there is both convergence and integration occurring within primary visual cortex. Second, primary visual cortex is involved in multisensory processes during early post-stimulus stages (as revealed by EEG/ERP/ERFs as well as TMS). Third, multisensory effects in primary visual cortex directly impact behaviour and perception, as revealed by correlational (EEG/ERPs/ERFs) as well as more causal measures (TMS/tACS). While the provocative claim of Ghazanfar and Schroeder (2006) that the whole of neocortex is multisensory in function has yet to be demonstrated, this can now be considered established in the case of the human primary visual cortex. PMID- 26275966 TI - Developing organisational ethics in palliative care. AB - BACKGROUND: Palliative carers constantly face ethical problems. There is lack of organised support for the carers to handle these ethical problems in a consistent way. Within organisational ethics, we find models for moral deliberation and for developing organisational culture; however, they are not combined in a structured way to support carers' everyday work. RESEARCH OBJECTIVE: The aim of this study was to describe ethical problems faced by palliative carers and develop an adapted organisational set of values to support the handling of these problems. RESEARCH DESIGN: Ethical problems were mapped out using focus groups and content analysis. The organisational culture were developed using normative analysis and focus group methodology within a participatory action research approach. Main participants and research context: A total of 15 registered nurses and 10 assistant nurses at a palliative unit (with 19 patient beds) at a major University Hospital in Sweden. Ethical considerations: The study followed standard ethics guidelines concerning informed consent and confidentiality. FINDINGS: We found six categories of ethical problems (with the main focus on problems relating to the patient's loved ones) and five categories of organisational obstacles. Based on these findings, we developed a set of values in three levels: a general level, an explanatory level and a level of action strategies. DISCUSSION: The ethical problems found corresponded to problems in other studies with a notable exception, the large focus on patient loved ones. The three-level set of values is a way to handle risks of formulating abstract values not providing guidance in concrete care voiced in other studies. CONCLUSION: Developing a three-level set of values adapted to the specific ethical problems in a concrete care setting is a first step towards a better handling of ethical problems. PMID- 26275972 TI - Prevalence of degenerative changes of the spine on magnetic resonance images and radiographs in patients aged 16-45 years with chronic back pain of short duration in the Spondyloarthritis Caught Early (SPACE) cohort. AB - OBJECTIVES: To determine the prevalence of degenerative changes (DCs) in the spine of young patients with back pain without axial spondyloarthritis (no axSpA), with possible axSpA (poss-axSpA) and with definite axSpA (axSpA), as shown on MRI and radiographs. METHODS: Whole-spine MRI and cervical and lumbar radiography were performed in patients >=16 years of age with chronic back pain (>=3 months, <=2 years, onset <45 years) and potential axSpA (Spondyloarthritis Caught Early cohort). Patients were classified as no-axSpA, poss-axSpA [not fulfilling the Assessment of Spondyloarthritis International Society (ASAS) axSpA criteria] or axSpA (fulfilling ASAS axSpA criteria). Images (MRI and X-rays) were evaluated on the presence of DCs by two independent readers, blinded to clinical and laboratory information as well as to the results of the other imaging modality. In cases of disagreement, a third reader served as adjudicator. A Chi square test was used to analyse differences between patient groups according to various selected cut-off points (1-3) of individual DCs. RESULTS: Of 274 patients (38% male, mean age: 29 years), 25 (9%) were classified as no-axSpA, 134 (48.9%) as poss-axSpA and 115 (42.0%) as axSpA. Two hundred and forty-five (89%) patients had DCs on MRI [21/25 (84%) no-axSpA, 121/134 (90%) poss-axSpA, 103/115 (90%) axSpA, P = 0.792], range 1-29 (median 5.5), and 121 (44%) patients had DCs on radiographs [13/25 (52%) no-axSpA, 62/134 (46%) poss-axSpA, 48/115 (42%) axSpA, P = 0.261], range 1-11 (median 2). Prevalence of DCs was similar between patient groups. DCs were predominantly found in the lumbar spine. CONCLUSION: Prevalence of DCs was high in this cohort of young patients with short-term chronic back pain, in accordance with the literature. Prevalence of DCs in no-axSpA patients, poss-axSpA patients and axSpA patients was found to be similar. PMID- 26275971 TI - Flow Velocity Mapping Using Contrast Enhanced High-Frame-Rate Plane Wave Ultrasound and Image Tracking: Methods and Initial in Vitro and in Vivo Evaluation. AB - Ultrasound imaging is the most widely used method for visualising and quantifying blood flow in medical practice, but existing techniques have various limitations in terms of imaging sensitivity, field of view, flow angle dependence, and imaging depth. In this study, we developed an ultrasound imaging velocimetry approach capable of visualising and quantifying dynamic flow, by combining high frame-rate plane wave ultrasound imaging, microbubble contrast agents, pulse inversion contrast imaging and speckle image tracking algorithms. The system was initially evaluated in vitro on both straight and carotid-mimicking vessels with steady and pulsatile flows and in vivo in the rabbit aorta. Colour and spectral Doppler measurements were also made. Initial flow mapping results were compared with theoretical prediction and reference Doppler measurements and indicate the potential of the new system as a highly sensitive, accurate, angle-independent and full field-of-view velocity mapping tool capable of tracking and quantifying fast and dynamic flows. PMID- 26275973 TI - The Eye on Mitochondrial Disorders. AB - Ophthalmologic manifestations of mitochondrial disorders are frequently neglected or overlooked because they are often not regarded as part of the phenotype. This review aims at summarizing and discussing the etiology, pathogenesis, diagnosis, and treatment of ophthalmologic manifestations of mitochondrial disorders. Review of publications about ophthalmologic involvement in mitochondrial disorders by search of Medline applying appropriate search terms. The eye is frequently affected by syndromic as well as nonsyndromic mitochondrial disorders. Primary and secondary ophthalmologic manifestations can be differentiated. The most frequent ophthalmologic manifestations of mitochondrial disorders include ptosis, progressive external ophthalmoplegia, optic atrophy, retinopathy, and cataract. More rarely occurring are nystagmus and abnormalities of the cornea, ciliary body, intraocular pressure, the choroidea, or the brain secondarily affecting the eyes. It is important to recognize and diagnose ophthalmologic manifestations of mitochondrial disorders as early as possible because most are accessible to symptomatic treatment with partial or complete short-term or long-term beneficial effect. Ophthalmologic manifestations of mitochondrial disorders need to be appropriately diagnosed to initiate the most effective management and guarantee optimal outcome. PMID- 26275974 TI - Resilience in Youth and Families Living With Pediatric Health and Developmental Conditions: Introduction to the Special Issue on Resilience. AB - This special issue of the Journal of Pediatric Psychology showcases a growing area of research with a collection of 16 contemporary studies of resilience in youth with chronic medical or developmental conditions and their families. The research reported in this special issue covers a broad range of pediatric populations, including cancer, type 1 diabetes, and chronic pain, among others, ranging in age from early childhood through early adulthood. This introduction to the special issue reviews the various ways the articles' authors conceptualize and define risk and resilience; most analyze protective processes in relation to resilient outcomes, including both achievement of explicitly positive experiences and avoidance of dysfunction or disruption. Challenges with measurement of resilience-related constructs is reviewed. Finally, the special issue editors offer a definition of resilience in the context of pediatric and health psychology. PMID- 26275975 TI - Psychometric Properties of the Psychosocial Assessment Tool-General in Adolescents and Young Adults With Sickle Cell Disease. AB - OBJECTIVES: Adolescents and young adults (AYAs) with sickle cell disease (SCD) experience psychosocial factors that increase their risk for poor disease management and health outcomes. Routine assessment of psychosocial factors that perpetuate health disparities is recommended. The Psychosocial Assessment Tool 2.0_General (PAT2.0_GEN) AYA is a psychosocial screener with potential clinical utility in AYAs with SCD. This article is a preliminary examination of the internal consistency and predictive validity of this measure in a sample of 45 AYAs with SCD. METHODS: Participants completed the PAT2.0_GEN AYA, Pediatric Quality of Life Inventory, and a demographics form; psychosocial referral data were also collected. RESULTS: Internal consistency for the PAT2.0_GEN AYA was acceptable except for the Family Beliefs (0.67) and Structure and Resources subscales (0.37). PAT2.0_GEN AYA scores were associated with an increased likelihood of referral for intervention within 4 months. CONCLUSIONS: The PAT2.0_GEN AYA holds promise as a screener to identify psychosocial risk factors that may compromise health outcomes in AYAs with SCD. PMID- 26275976 TI - Parent-Child Injury Prevention Conversations Following a Trip to the Emergency Department. AB - OBJECTIVES: The goal of the study was to examine how parents use conversation to promote the internalization of safety values after their child has been seriously injured. METHODS: Parent interviews detailing postinjury conversations were coded for strategies mentioned to prevent injuries in the future and information about circumstances surrounding the injury. RESULTS: Logistic regression analyses revealed that parents were more likely to discuss why an activity was dangerous with older than younger children, and were more likely to urge daughters than sons to be more careful in the future. Injuries resulting from the presence of environmental hazards predicted parents telling children to be more careful in the future. Having others involved predicted parents urging children not to engage in the behavior again. CONCLUSIONS: Findings suggest that parents modulated strategies according to age, gender, and injury circumstances to maximize the likelihood that children would behave differently in the future. PMID- 26275977 TI - Medical and Psychosocial Correlates of Insomnia Symptoms in Adult Survivors of Pediatric Brain Tumors. AB - OBJECTIVE: Children diagnosed with brain tumors are at risk for insomnia. We evaluated insomnia symptoms, medical and psychosocial correlates, and medical documentation of sleep-related issues in a neuro-oncology clinic. METHODS: 98 adult survivors of pediatric brain tumors provided data about sleep, psychological distress, and health-related quality of life. Medical records were reviewed for treatment-related information and for documentation of sleep-related issues. RESULTS: 26% of the sample reported insomnia symptoms as evidenced by poor sleep efficiency. Insomnia symptoms were associated with a migraine headache history, but not with other medical or psychosocial outcomes. Approximately one in three medical providers did not document discussing sleep during the survivorship visit. CONCLUSIONS: A sizeable number of pediatric brain tumor survivors experience insomnia symptoms. The survivorship visit is an ideal opportunity for providers to conduct a sleep evaluation for this at-risk population and to provide referrals for evidence-based insomnia treatment. PMID- 26275978 TI - Determinants of rupture of the unscarred uterus and the related feto-maternal outcome: current scenario in a low-income country. AB - BACKGROUND: Rupture of the gravid uterus is one of the most grievous obstetric events accounting for considerable maternal morbidity and mortality. MATERIALS AND METHODS: An audit over a period of 2 years from October 2010 to September 2012 was performed on pregnant women irrespective of gestational age who had a uterine rupture of a uterus, presumed to be unscarred. RESULTS: There were 141 ruptures among 43,886 deliveries (0.3%). Of those, 18 (12.8% of the ruptures and 0.04% of the deliveries) occurred in presumed unscarred uteri. The aetiologies were: obstruction 50%, uterine anomaly 22.2%, oxytocic administration 16.6 %, instrumental deliveries 5.5% and miscellaneous 11.1 %. Hysterectomy was performed in 55.6% of cases. Fetal mortality was 83.3% and maternal mortality was 16.6%. CONCLUSIONS: Training of traditional birth attendants for early referrals, screening for uterine anomalies by ultrasound in early pregnancy and counselling the women, especially multiparas and grand-multiparas are mandatory. Oxytocin should only be used for those if the doctor who prescribed its use stays with the patient continuously and stops oxytocics as soon as there are reasonable contractions. In emergency, the decision to delivery time should be less than 30 min. These are some ways through which a tragic event like uterine rupture and its consequences can be averted. PMID- 26275979 TI - International Society for Quality of Life Research commentary on the draft European Medicines Agency reflection paper on the use of patient-reported outcome (PRO) measures in oncology studies. AB - In 2014, the European Medicines Agency (EMA) released for comment a draft reflection paper on the use of patient-reported outcome (PRO) measures in oncology studies. A twelve-member International Society for Quality of Life Research (ISOQOL) taskforce was convened to coordinate the ISOQOL response. Twenty-one ISOQOL members provided detailed comments and suggestions on the paper: 81 % from academia and 19 % from industry. Taskforce members consolidated and further refined these comments and shared the recommendations with the wider ISOQOL membership. A final response was submitted to the EMA in November 2014. The impending publication of the EMA reflection paper presents a valuable opportunity for ISOQOL to comment on the current direction of EMA PRO guidance and strategy. The EMA paper, although focused on cancer, could serve as a model for using PROs in other conditions, as it provides a useful update surrounding some of the design issues common to all trial research including PRO endpoints. However, we believe there are a number of additional areas in need of greater consideration. The purpose of this commentary is therefore to highlight the strengths of this timely and potentially useful document, but also to outline areas that may warrant further discussion. PMID- 26275981 TI - Selvester QRS scoring in conduction abnormalitites: Caution recommended due to recent findings. PMID- 26275980 TI - Validation of the Full and Short-Form Self-Help Involvement Scale Against the Rasch Measurement Model. AB - BACKGROUND: Substance use disorders (SUDs) are one of the nation's most costly problems in terms of dollars, disability, and death. Self-help programs are among the varied recovery support options available to address SUD, and evaluation of these programs depends on good measurement. There exists an unmet need for a psychometrically sound, brief, efficient measure of self-help involvement for individuals with SUD that is valid across different substances and age-groups. METHODS: Using data from 2,101 persons presenting for SUD treatment, the full 21 item Global Appraisal of Individual Needs Self-Help Involvement Scale (SHIS) and a newly developed 11-item short-form version were validated against the Rasch measurement model and each other. Differential item functioning (DIF) was assessed by primary substance and age. RESULTS: Both versions met Rasch psychometric criteria. The full scale had minor misfit with no DIF for alcohol, marijuana, or opioids but a few instances of DIF for amphetamine and cocaine users as well as for age, in that youth tended to endorse several easier items more frequently than did adults. The 11-item short form had neither misfit nor DIF by substance and only minor DIF by age was highly correlated with the full version and was relatively more efficient. Criterion-related validity was supported for both. CONCLUSIONS: Both the long and short versions of SHIS are psychometrically sound measures of a more comprehensive conceptualization of self help involvement for SUDs that can be used as part of an in-depth assessment or as a short measure that lessens respondent burden. PMID- 26275982 TI - Non-invasive assessment of the effect of beta blockers and calcium channel blockers on the AV node during permanent atrial fibrillation. AB - AIM: We aimed at assessing changes in AV nodal properties during administration of the beta blockers metoprolol and carvedilol, and the calcium channel blockers diltiazem and verapamil from electrocardiographic data. METHODS: Parameters accounting for the functional refractory periods of the slow and fast pathways (aRPs and aRPf) were estimated using atrial fibrillatory rate (AFR) and ventricular response assessed from 15-min ECG segments recorded at baseline and on drug treatment from sixty patients with permanent AF. RESULTS: The results showed that AFR and HR were significantly reduced for all drugs, and that aRPs and aRPf were significantly prolonged in both pathways. The prolongation in aRP was significantly larger for the calcium channel blockers than for the beta blockers. CONCLUSIONS: The changes observed in the AV node parameters are in line with the results of previous electrophysiological studies performed in patients during sinus rhythm, therefore supporting the clinical value of the method. PMID- 26275983 TI - The spatial QRS-T angle outperforms the Italian and Seattle ECG-based criteria for detection of hypertrophic cardiomyopathy in pediatric patients. AB - INTRODUCTION: The spatial peaks QRS-T angle has been shown to differentiate adult patients with hypertrophic cardiomyopathy (HCM) from controls. We hypothesized that the spatial peaks QRS-T angle would, in isolation, be more accurate than the Italian 12-lead ECG Pre-participation Screening criteria or the Seattle criteria for detecting hypertrophic cardiomyopathy (HCM) in pediatric patients. METHODS: A retrospective study of pediatric patients with HCM compared to age and gender matched control patients was undertaken. Significance, odds ratios, sensitivity and specificity of HCM detection of the visually derived spatial peaks QRS-T angle were compared to those of traditional 12-lead ECG criteria using: 1) Italy's National Pre-participation Screening Programme criteria; and 2) described criteria from Seattle. RESULTS: ECG results from 130 pediatric HCM patients (14.2+/-4.4years) were compared to 470 control patients (normal echocardiograms, mean age 13.4+/-4.6years). Mean+/-standard deviation (SD) values for spatial peaks QRS-T angles were 120.4+/-40.7 and 21.3+/-13.7 degrees for HCM and controls, respectively (P<0.001). A spatial peaks QRS-T angle cutoff value of >54.9 degrees yielded greater sensitivity and specificity (93.1% and 98.7%, respectively) for detecting HCM over ECG criteria from Italy (68.5% and 48.1%, respectively) or Seattle (64.6% and 78.9%, respectively) with odds ratios at 1039.70 (95% CI 363.03 to 2977.67), 2.01 (95% CI 1.33 to 3.04) and 6.84 (4.49 10.44), respectively. CONCLUSION: In our cohort, a visually derived spatial peaks QRS-T angle has increased sensitivity and specificity for detection of HCM in pediatric patients compared to currently utilized Italian or Seattle ECG criteria. PMID- 26275984 TI - Urine oligosaccharide pattern in patients with hyperprolactinaemia. AB - Free milk-type oligosaccharides are produced during pregnancy and lactation and may have an impact on several cells in the immune system. Our aim was to investigate if patients with isolated hyperprolactinaemia, not related to pregnancy, also have increased synthesis and urinary excretion of milk-type oligosaccharides and to compare the excretion pattern with that found during pregnancy. Urine samples were collected as morning sample from 18 patients with hyperprolactinaemia, 13 healthy controls with normal prolactin levels and four pregnant women. After purification, lactose and free oligosaccharides were analysed and quantified by high-performance anion-exchange chromatography with pulsed amperometric detection. The identity of peaks was confirmed by exoglycosidase treatment and comparison with oligosaccharide standards. Prolactin was measured in serum collected between 09 and 11 a.m. by a standardized immunochemical method. Patients with hyperprolactinaemia had higher urinary excretion of lactose than normoprolactinemic controls and urinary lactose correlated positively to prolactin levels (r = 0.51, p < 0.05). Increased levels of the fucosylated oligosaccharides 2-fucosyl lactose and lacto-di-fucotetraose were found in urine from three and two patients, respectively. The acidic oligosaccharide 3-sialyl lactose was found in high amount in urine from two patients with prolactin of >10,000 mU/l. However, pregnant women in their third trimester had the highest concentration of all these oligosaccharides and excretion increased during pregnancy. This study is first to show that both lactose and certain fucosylated and sialylated milk-type oligosaccharides are increased in some patients with hyperprolactinaemia. It remains to elucidate the functional importance of these findings. PMID- 26275986 TI - Flexible data analysis and evaluations of the SFP 10-14. PMID- 26275985 TI - Preparation and characterization of heparin hexasaccharide library with N unsubstituted glucosamine residues. AB - The rare N-unsubstituted glucosamine (GlcNH3(+)) residues in heparan sulfate (HS) have important biological and pathophysiological roles. Therefore, the ability to chemically generate a series of oligosaccharides, which have a similar structure to the naturally-occurring, GlcNH3(+)--containing oligosaccharides from HS, would greatly contribute to investigating their natural role in HS. In this study, a hexasaccharide library that possess GlcNH3(+) residues were prepared from the chemical modification of the fully sulfated dp6. Chemical reaction conditions were optimized to generate different pattern of GlcNH3(+)--containing oligosaccharides, then the structure of the library was detected by high performance liquid chromatography-ion trap/time-of-flight mass spectrometry (LC/MS-ITTOF) analysis. EIC/MS and MS(2) analysis showed different fragmentation patterns of dp6s with different GlcNH3(+) residues. This provides a foundation for further identification and quantification of GlcNH3(+)--oligosaccharides by mass spectrum analysis. PMID- 26275987 TI - Social adversities in adolescence predict unfavourable trajectories of internalized mental health symptoms until middle age: results from the Northern Swedish Cohort. AB - BACKGROUND: Experiencing adversities during upbringing has short-term and long term effects on mental health. This study aims to explore how social adversities in adolescence predict trajectories of internalized mental health symptoms (IMHS), from adolescence and onward until middle age. METHODS: Based on 1040 individuals from the Northern Swedish Cohort Study, a community-based cohort with 27 years of follow-up. We applied latent class growth analysis to extract trajectories of IMHS between ages 16 and 43. Multinomial logistic regression was used to study the association of social adversities (residential mobility, residential crowding, parental loss, unemployment of a parent, physical illness of a parent, mental illness or alcohol problems of a parent) in adolescence with IMHS trajectories. RESULTS: Five trajectory classes were identified: 'very low stable' (26% of the sample), 'low stable' (58%), 'moderate stable' (5%), 'increasing' (8%) and 'high decreasing' (3%). Both in men and women, reporting social adversities at the age of 16 increased the risk of belonging to the classes with less favourable development of IMHS. Reporting adversities was positively associated with the initial level of the IMHS trajectories. Thus it seems that the influence of adversities is more pronounced during the early years of follow-up and is attenuated over time. CONCLUSION: Experiencing social adversities in adolescence increases the risk of entering unfavourable developmental trajectories of mental health until middle age. PMID- 26275988 TI - [Catheter-associated urinary tract infections]. AB - In patients with indwelling urethral catheters significant bacteriuria develops within 4 weeks of indwelling time in practically 100% of the cases. Catheter encrustation and obstruction can occur in approximately 40% of patients. Symptomatic ascending urinary tract infections, urethral complications and urolithiasis can occur in significant numbers in the long term. Regular educational and surveillance programs in nursing homes, hospitals and in home care are important to instruct personnel in hygiene procedures, to learn the indications for catheterization, to keep the indwelling time of catheters as short as possible, to detect any complications early and to initiate appropriate diagnostics and therapy by the urologist. PMID- 26275989 TI - Wheat mitogen-activated protein kinase gene TaMPK4 improves plant tolerance to multiple stresses through modifying root growth, ROS metabolism, and nutrient acquisitions. AB - KEY MESSAGE: Wheat MAPK member TaMPK4 responds to abiotic stresses of Pi and N deprivations and high salinity and is crucial in regulating plant tolerance to aforementioned stresses. Mitogen-activated protein kinase (MAPK) cascades are important signal transduction modules in regulating plant responses to various environmental stresses. In this study, a wheat MAPK member referred to TaMPK4 was characterized for its roles in mediating plant tolerance to diverse stresses. TaMPK4 shares conserved domains generally identified in plant MAPKs and possesses in vitro kinase activity. Under stresses of Pi and N deprivations and high salinity, TaMPK4 was strongly upregulated and its expressions were restored upon recovery treatments from above stresses. Sense- and antisense-expressing TaMPK4 in tobacco significantly modified plant growth under the stress conditions and dramatically modified the root architecture through transcriptional regulation of the auxin transport-associated genes NtPIN3 and NtPIN9, whose downregulated expressions dramatically reduced the root growth. Compared with wild type (WT), the antioxidant enzymatic activities under the stress conditions, P accumulation under P deprivation, and N amount under N deficiency were altered dramatically in the transgenic plants, showing higher in the TaMPK4-overexpressing and lower in the TaMPK4-knockout plants, which were in concordance with the modified expressions of a set of antioxidant enzyme genes (NtPOD2;1, NtPOD9, NtSOD2, NtFeSOD, and NtCAT), two phosphate transporter genes (NtPT and NtPT2), and two nitrate transporter genes (NtNRT1.1-s and NtNRT1.1-t), respectively. Downregulated expression of above genes in tobacco largely reduced the plant growth, and Pi and N acquisitions under the stress conditions. TaMPK4 also involved regulations of plant K(+) and osmolyte contents under high salinity. Thus, TaMPK4 is functional in regulating plant tolerance to diverse stresses through modifying various biological processes. PMID- 26275992 TI - Direct Evaluation of the Quantum Confinement Effect in Single Isolated Ge Nanocrystals. AB - To address the yet open question regarding the nature of quantum confinement in Ge nanocrystals (Ge NCs) we employed scanning tunneling spectroscopy to monitor the electronic structure of individual isolated Ge NCs as a function of their size. The (single-particle) band gaps extracted from the tunneling spectra increase monotonically with decreasing nanocrystal size, irrespective of the capping ligands, manifesting the effect of quantum confinement. Band-gap widening of ~1 eV with respect to the bulk value was observed for Ge-NCs 3 nm in diameter. The picture emerging from comparison with theoretical calculations and other experimental results is discussed. PMID- 26275991 TI - De novo assembly and characterisation of the field pea transcriptome using RNA Seq. AB - BACKGROUND: Field pea (Pisum sativum L.) is a cool-season grain legume that is cultivated world-wide for both human consumption and stock-feed purposes. Enhancement of genetic and genomic resources for field pea will permit improved understanding of the control of traits relevant to crop productivity and quality. Advances in second-generation sequencing and associated bioinformatics analysis now provide unprecedented opportunities for the development of such resources. The objective of this study was to perform transcriptome sequencing and characterisation from two genotypes of field pea that differ in terms of seed and plant morphological characteristics. RESULTS: Transcriptome sequencing was performed with RNA templates from multiple tissues of the field pea genotypes Kaspa and Parafield. Tissue samples were collected at various growth stages, and a total of 23 cDNA libraries were sequenced using Illumina high-throughput sequencing platforms. A total of 407 and 352 million paired-end reads from the Kaspa and Parafield transcriptomes, respectively were assembled into 129,282 and 149,272 contigs, which were filtered on the basis of known gene annotations, presence of open reading frames (ORFs), reciprocal matches and degree of coverage. Totals of 126,335 contigs from Kaspa and 145,730 from Parafield were subsequently selected as the reference set. Reciprocal sequence analysis revealed that c. 87% of contigs were expressed in both cultivars, while a small proportion were unique to each genotype. Reads from different libraries were aligned to the genotype-specific assemblies in order to identify and characterise expression of contigs on a tissue-specific basis, of which 87% were expressed in more than one tissue, while others showed distinct expression patterns in specific tissues, providing unique transcriptome signatures. CONCLUSION: This study provided a comprehensive assembled and annotated transcriptome set for field pea that can be used for development of genetic markers, in order to assess genetic diversity, construct linkage maps, perform trait-dissection and implement whole-genome selection strategies in varietal improvement programs, as well to identify target genes for genetic modification approaches on the basis of annotation and expression analysis. In addition, the reference field pea transcriptome will prove highly valuable for comparative genomics studies and construction of a finalised genome sequence. PMID- 26275993 TI - Surgical Approaches to Pediatric Ureteropelvic Junction Obstruction. AB - Approximately 10-30% of infants with hydronephrosis are found to have ureteropelvic junction (UPJ) obstruction. Technological advances in imaging have allowed physicians to better identify the location of the obstruction. The classic repair is the Anderson-Hynes repair which shows a 90-100% success rate and appears superior to many less complex techniques. Is it best to approach this repair through an open incision or laparoscopically with or without a surgical robot? That question remains to be answered and largely depends on how you define "best." PMID- 26275994 TI - Hydrogen Sulfide Promotes Tet1- and Tet2-Mediated Foxp3 Demethylation to Drive Regulatory T Cell Differentiation and Maintain Immune Homeostasis. AB - Regulatory T (Treg) cells are essential for maintenance of immune homeostasis. Here we found that hydrogen sulfide (H2S) was required for Foxp3(+) Treg cell differentiation and function and that H2S deficiency led to systemic autoimmune disease. H2S maintained expression of methylcytosine dioxygenases Tet1 and Tet2 by sulfhydrating nuclear transcription factor Y subunit beta (NFYB) to facilitate its binding to Tet1 and Tet2 promoters. Transforming growth factor-beta (TGF beta)-activated Smad3 and interleukin-2 (IL-2)-activated Stat5 facilitated Tet1 and Tet2 binding to Foxp3. Tet1 and Tet2 catalyzed conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in Foxp3 to establish a Treg-cell specific hypomethylation pattern and stable Foxp3 expression. Consequently, Tet1 and Tet2 deletion led to Foxp3 hypermethylation, impaired Treg cell differentiation and function, and autoimmune disease. Thus, H2S promotes Tet1 and Tet2 expression, which are recruited to Foxp3 by TGF-beta and IL-2 signaling to maintain Foxp3 demethylation and Treg-cell-associated immune homeostasis. PMID- 26275996 TI - Utilization of Observation Units for the Care of Poisoned Patients: Trends from the Toxicology Investigators Consortium Case Registry. AB - Many poisoned patients may only require a period of observation after their exposure. There are limited data describing the use of observation units for managing poisoned adult and pediatric patients. We performed a retrospective review of all patients reported to the ToxIC Case Registry between January 1, 2012 and December 31, 2013. Eligible patients included those who received a bedside consultation by a medical toxicologist and whose care was provided in an observation unit, or those who were admitted under the care of a medical toxicologist in an observation unit. A total of 15,562 poisonings were reported to the registry during the study period, of which 340 (2.2 %) involved patients who were cared for in an observation unit. Of these patients, 22.1 % were 18 years of age or younger, and the remaining 77.9 % were greater than 18 years of age. The most common reason for exposure was the intentional ingestion of a pharmaceutical agent in both adult (30.2 %) and pediatric patients (36.0 %). Alcohols (ethanol) (24.9 %), opioids (20.0 %), and sedative-hypnotics (17.7 %) were the most common agent classes involved in adult patient exposures. The most common agent classes involved in pediatric exposures were antidepressants (12.0 %), anticonvulsants (10.7 %), and envenomations (10.7 %). In adult patients, the most common signs and symptoms involved the nervous system (52.0 %), a toxidrome (17.0 %), or a major vital sign abnormality (14.7 %). In pediatric patients, the most common signs and symptoms involved the nervous system (53.3 %), a toxidrome (21.3 %), or a major vital sign abnormality (17.3 %). The results of this study demonstrate that a wide variety of poisoned patients have been cared for in an observation unit in consultation with a board-certified medical toxicologist. Patterns for the reasons for exposure, agents responsible for the exposure, and toxicological treatments will continue to evolve. Further study is needed to identify better those poisoned patients who can be appropriately managed in an observation unit. PMID- 26275995 TI - The PYRIN Domain-only Protein POP1 Inhibits Inflammasome Assembly and Ameliorates Inflammatory Disease. AB - In response to infections and tissue damage, ASC-containing inflammasome protein complexes are assembled that promote caspase-1 activation, IL-1beta and IL-18 processing and release, pyroptosis, and the release of ASC particles. However, excessive or persistent activation of the inflammasome causes inflammatory diseases. Therefore, a well-balanced inflammasome response is crucial for the maintenance of homeostasis. We show that the PYD-only protein POP1 inhibited ASC dependent inflammasome assembly by preventing inflammasome nucleation, and consequently interfered with caspase-1 activation, IL-1beta and IL-18 release, pyroptosis, and the release of ASC particles. There is no mouse ortholog for POP1, but transgenic expression of human POP1 in monocytes, macrophages, and dendritic cells protected mice from systemic inflammation triggered by molecular PAMPs, inflammasome component NLRP3 mutation, and ASC danger particles. POP1 expression was regulated by TLR and IL-1R signaling, and we propose that POP1 provides a regulatory feedback loop that shuts down excessive inflammatory responses and thereby prevents systemic inflammation. PMID- 26275998 TI - Lavage prior to vertebral augmentation reduces the risk for cement leakage. AB - PURPOSE: This study aimed at assessing the cement leakage rate and the filling pattern in patients treated with vertebroplasty, kyphoplasty and stentoplasty with and without a newly developed lavage technique. STUDY DESIGN: Retrospective clinical case-control study. METHODS: A newly developed bipedicular lavage technique prior to cement application was applied in 64 patients (45.1 %) with 116 vertebrae, ("lavage" group). A conventional bipedicular cement injection technique was used in 78 patients (54.9 %) with 99 levels ("controls"). The outcome measures were filling patterns and leakage rates. RESULTS: The overall leakage rate (venous, cortical defect, intradiscal) was 37.9 % in the lavage and 83.8 % in the control group (p < 0.001). Venous leakage (lavage 12.9 % vs. controls 31.3 %; p = 0.001) and cortical defect leakage (lavage 17.2 % vs. controls 63.3 %; p < 0.001) were significantly lower in the lavage group compared to "controls," whereas intradiscal leakages were similar in both groups (lavage 12.1 % vs. controls 15.2 %; p = 0.51). For venous leakage multivariate logistic regression analysis showed lavage to be the only independent predictor. Lavage was associated with 0.33-times (95 % CI 0.16-0.65; p = 0.001) lower likelihood for leakage in compared to controls. CONCLUSIONS: Vertebral body lavage prior to cement augmentation is a safe technique to reduce cement leakage in a clinical setting and has the potential to prevent pulmonary fat embolism. Moreover, a better filling pattern can be achieved. PMID- 26276000 TI - Towards the creation of a standard MSC line as a calibration tool. PMID- 26275999 TI - How do Malawian women rate the quality of maternal and newborn care? Experiences and perceptions of women in the central and southern regions. AB - BACKGROUND: While perceived quality of care is now widely recognized to influence health service utilization, limited research has been conducted to explore and measure perceived quality of care using quantitative tools. Our objective was to measure women's perceived quality of maternal and newborn care using a composite scale and to identify individual and service delivery factors associated with such perceptions in Malawi. METHODS: We conducted a cross-sectional survey in selected health facilities from March to May 2013. Exit interviews were conducted with 821 women convenience sampled at antenatal, delivery, and postnatal clinics using structured questionnaires. Experiences and the corresponding perceived quality of care were measured using a composite perception scale based on 27 items, clustered around three dimensions of care: interpersonal relations, conditions of the consultation and delivery rooms, and nursing care services. Statements reflecting the 27 items were read aloud and the women were asked to rate the quality of care received on a visual scale of 1 to 10 (10 being the highest score). For each dimension, an aggregate score was calculated using the un-weighted item means, representing three outcome variables. Descriptive statistics were used to display distribution of explanatory variables and one-way analysis of variance was used to analyse bivariate associations between the explanatory and the outcome variables. RESULTS: A high perceived quality of care rating was observed on interpersonal relations, conditions of the examination rooms and nursing care services with an overall mean score of 9/10. Self introduction by the health worker, explanation of examination procedures, consent seeking, encouragement to ask questions, confidentiality protection and being offered to have a guardian during delivery were associated with a high quality rating of interpersonal relations for antenatal and delivery care services. Being literate, never experienced a still birth and, first ANC visit were associated with a high quality rating of room conditions for antenatal care service. CONCLUSIONS: The study highlights some of the multiple factors associated with perceived quality of care. We conclude that proper interventions or practices and policies should consider these factors when making quality improvements. PMID- 26276001 TI - Research using Mesenchymal Stem/Stromal Cells: quality metric towards developing a reference material. AB - Mesenchymal stem/stromal cells (MSCs) have been extensively investigated for their regenerative, immune-modulatory, and wound healing properties. While the laboratory studies have suggested that MSC's have a unique potential for modulating the etiopathology of multiple diseases, the results from clinical trials have not been encouraging or reproducible. One of the explanations for such variability is explained by the "art" of isolating and propagating MSCs. Therefore, establishing more than minimal criteria to define MSC would help understand best protocols to isolate, propagate and deliver MSCs. Developing a calibration standard, a database and a set of functional tests would be a better quality metric for MSCs. In this review, we discuss the importance of selecting a standard, issues associated with coming up with such a standard and how these issues can be mitigated. PMID- 26276002 TI - Enhancement of the immunoregulatory potency of mesenchymal stromal cells by treatment with immunosuppressive drugs. AB - BACKGROUND AIMS: Multipotent mesenchymal stromal cells (MSCs) are distinguished by their ability to differentiate into a number of stromal derivatives of interest for regenerative medicine, but they also have immunoregulatory properties that are being tested in a number of clinical settings. METHODS: We show that brief incubations with rapamycin, everolimus, FK506 or cyclosporine A increase the immunosuppressive potency of MSCs and other cell types. RESULTS: The treated MSCs are up to 5-fold more potent at inhibiting the induced proliferation of T lymphocytes in vitro. We show that this effect probably is due to adsorption of the drug by the MSCs during pre-treatment, with subsequent diffusion into co cultures at concentrations sufficient to inhibit T-cell proliferation. MSCs contain measurable amounts of rapamycin after a 15-min exposure, and the potentiating effect is blocked by a neutralizing antibody to the drug. With the use of a pre-clinical model of acute graft-versus-host disease, we demonstrate that a low dose of rapamycin-treated but not untreated umbilical cord-derived MSCs significantly inhibit the onset of disease. CONCLUSIONS: The use of treated MSCs may achieve clinical end points not reached with untreated MSCs and allow for infusion of fewer cells to reduce costs and minimize potential side effects. PMID- 26276003 TI - Bone marrow stromal cell transplantation through tail vein injection promotes angiogenesis and vascular endothelial growth factor expression in cerebral infarct area in rats. AB - BACKGROUND AIMS: This study sought to identify correlations between vascular endothelial growth factor (VEGF) expression after tail-vein injection of rat derived bone marrow stromal cells (BMSCs) and neurogenesis and angiogenesis in cerebral infarct of rats. METHODS: Rats with intraluminal middle cerebral artery occlusion were injected in a tail vein with Hoechst-labeled BMSCs. Functional recovery from cerebral infarction was observed through the use of a locomotion score. The brains of injected rats were sliced, and Hoechst-labeled BMSCs in the infarct and peri-infarct areas and subventricular zone (SVZ) were detected with the use of fluorescence microscopy. Ki-67 (as a cell proliferation marker) and VEGF expression were determined by means of immunohistochemistry. Neurofibril formation and angiogenesis were examined by means of Bielschowsky staining. RESULTS: Within 1 to 2 weeks after BMSC injection, rats showed significantly improved locomotion scores compared with rats without BMSC injection (P < 0.01). Viable BMSCs were found in the peri-infarct area. The numbers of Ki-67-positive and VEGF-positive cells in the peri-infarct area and SVZ of injected rats were significantly increased compared with the control group (P < 0.01). Numerous new vessels, neurofibrils and anastomosed vasculatures were present in the infarct area. These neurofibrils mainly surrounded the neovasculatures. CONCLUSIONS: These results indicate that BMSC-transplantation in rats through tail vein injection can increase neurogenesis, perhaps as the result of VEGF-mediated and/or Ki-67-mediated angiogenesis. PMID- 26276004 TI - BMP4 inhibits myogenic differentiation of bone marrow-derived mesenchymal stromal cells in mdx mice. AB - BACKGROUND AIMS: Bone marrow-derived mesenchymal stromal cells (BMSCs) are a promising therapeutic option for treating Duchenne muscular dystrophy (DMD). Myogenic differentiation occurs in the skeletal muscle of the mdx mouse (a mouse model of DMD) after BMSC transplantation. The transcription factor bone morphogenic protein 4 (BMP4) plays a crucial role in growth regulation, differentiation and survival of many cell types, including BMSCs. We treated BMSCs with BMP4 or the BMP antagonist noggin to examine the effects of BMP signaling on the myogenic potential of BMSCs in mdx mice. METHODS: We added BMP4 or noggin to cultured BMSCs under myogenic differentiation conditions. We then injected BMP4- or noggin-treated BMSCs into the muscles of mdx mice to determine their myogenic potential. RESULTS: We found that the expression levels of desmin and myosin heavy chain decreased after treating BMSCs with BMP4, whereas the expression levels of phosphorylated Smad, a downstream target of BMP4, were higher in these BMSCs than in the controls. Mdx mouse muscles injected with BMSCs pretreated with BMP4 showed decreased dystrophin expression and increased phosphorylated Smad levels compared with muscles injected with non-treated BMSCs. The opposite effects were seen after pretreatment with noggin, as expected. CONCLUSIONS: Our results identified BMP/Smad signaling as an essential negative regulator of promyogenic BMSC activity; inhibition of this pathway improved the efficiency of BMSC myogenic differentiation, which suggests that this pathway might serve as a target to regulate BMSC function for better myogenic differentiation during treatment of DMD and degenerative skeletal muscle diseases. PMID- 26276005 TI - Storage effect on viability and biofunctionality of human adipose tissue-derived stromal cells. AB - BACKGROUND AIMS: In our recent studies, the transplantation of human adipose tissue-derived stromal cells (ASCs) has shown promise for treatment of diseases related to bone and joint disorders. METHODS: For the current clinical applications, ASCs were formulated and suspended in PlasmaLyte A supplemented with heparin, glucose and human serum albumin, balanced to pH 7.4 with sodium bicarbonate. This cell solution constitutes 20% of the overall transplanted mixture and is supplemented with hyaluronic acid (60%) and OraGraft particles (20%). We intended to investigate the effect of this transplantation mixture on the viability and biofunctionality of ASCs in bone formation. Freshly harvested cells were resuspended and incubated in the indicated mixture for up to 48 h at 4 degrees C. Cell viability was assessed using trypan blue and AlamarBlue, and cell functionality was determined by quantifying their adhesion rate in vitro and bone formation in an ectopic mouse model. RESULTS: More than 80% of the ASCs stored in the transplantation mixture were viable for up to 24 h. Cell viability beyond 24 h in storage decreased to approximately 50%. In addition, an equal degree of bone formation was observed between the cells transplanted following incubation in transplantation mixture for up to 24 h and zero-time non-incubated cells (control). CONCLUSIONS: The viability and functionality of ASCs stored in the presented formulation will make such cell therapy accessible to larger and more remote populations. PMID- 26276006 TI - Paracrine in vivo inhibitory effects of adipose tissue-derived mesenchymal stromal cells in the early stages of the acute inflammatory response. AB - BACKGROUND AIMS: Excessive or unresolved inflammation leads to tissue lesions. Adipose tissue-derived mesenchymal stromal cells (AMSCs) have shown protective effects that may be dependent on the modulation of inflammation by secreted factors. METHODS: We used the zymosan-induced mouse air pouch model at two time points (4 h and 18 h) to evaluate the in vivo effects of AMSCs and their conditioned medium (CM) on key steps of the early inflammatory response. We assessed the effects of AMSCs and CM on leukocyte migration and myeloperoxidase activity. The levels of chemokines, cytokines and eicosanoids in exudates were measured by use of enzyme-linked immunoassay or radio-immunoassay. In addition, the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 (mPGES-1) was studied by use of Western blotting and the phosphorylation of p65 nuclear factor-kappaB (NF-kappaB) by immunofluorescence. RESULTS: All inflammatory parameters were significantly reduced by CM and AMSCs to a similar extent at 4 h after zymosan injection with lower effects at 18 h. The observed inhibition of leukocyte migration was associated with reduced levels of chemokines and leukotriene B4. Interleukin-1beta, interleukin-6, tumor necrosis factor-alpha and tumor necrosis factor-stimulated gene 6 levels were significantly decreased. The downregulation of mPGES-1 was associated with inhibition of prostaglandin E2 production. Our results suggest that these anti inflammatory effects are related, in part, to the inhibition of NF-kappaB activation. CONCLUSIONS: AMSCs dampen the early process of inflammation in the zymosan-induced mouse air pouch model through paracrine mechanisms. These results support the potential utility of these cells as a source of novel treatment approaches for inflammatory pathologies. PMID- 26276007 TI - MyD88-silenced dendritic cells induce T-cell hyporesponsiveness and promote Th2 polarization in vivo. AB - BACKGROUND AIMS: Previous studies have determined that the absence of MyD88 enhances the tolerogenicity of dendritic cells (DCs), suggesting that inhibiting innate immunity may be a potential strategy to facilitate the induction of transplant tolerance by DCs. However, the underlying mechanism remains unclear. METHODS: Recipient rats were preconditioned with MyD88 gene-silenced DCs. In vivo distribution of infused MyD88 gene-silenced DCs in lymphatic organs was also analyzed. The response ability of recipient spleen T cells was determined by cell proliferation assay. The concentrations of interferon (IFN)-gamma, interleukin (IL)-2, IL-4, IL-5 and IL-10 in cell culture supernates were measured with sandwich enzyme-linked immunosorbent assay. Flow cytometry was used to detect the transfection efficiency and CD4(+)CD25(+)FoxP3(+) T cell assay. RESULTS: After being infused into allogenic recipient rats, both MyD88-or control-silenced DCs were efficiently trafficked to the lymphatic organs and liver. The ex vivo analysis of proliferative responses revealed the donor-specific inhibition of alloimmune reactivity by MyD88-silenced DCs. This effect was associated with the marked inhibition of Th1-type cytokine production (IFN-gamma and IL-2) but with significant promotion of Th2 type cytokine secretion (IL-4 and IL-5). CONCLUSIONS: It was demonstrated that T cells from recipients pretreated with MyD88-silenced DCs exhibited significantly reduced secretion of IFN-gamma and IL 2 but markedly enhanced production of IL-4 and IL-5. PMID- 26276008 TI - An innovative method to generate a Good Manufacturing Practice-ready regulatory T cell product from non-mobilized leukapheresis donors. AB - BACKGROUND AIMS: There is real and sustained interest in preparing T-regulatory cells from leukapheresis collections for cellular therapy through the use of simple, effective and reliable methods conforming to Good Manufacturing Practice (GMP). We describe a GMP-ready isolation procedure for CD25(+) products with the use of a sterile docking device, pigtail sampling, a laminar flow hood and the CliniMACS system that uses leukapheresis collections made by two apheresis machines. METHODS: We used CD8/CD19 depletion followed by CD25-positive selection. The median number of CD4(+) cells recovered was 72.5 +/- 32.6 * 10(6), of which 60.5% +/- 17.8% were CD25(+)FOXP3(+) cells. Suppression of autologous CD25(-) cell proliferation by the cryopreserved CD25(+) products was 51.3% +/- 4.4%, 49.0% +/- 3.7% and 39.0% +/- 3.6% at CD25(+):CD25(-) ratios of 1:1, 1:2 and 1:4 (n = 6), respectively, comparable to suppression by fresh CD25(+) products (53% +/- 6.2%, 51% +/- 3.3% and 39% +/- 7.1%). RESULTS: We found Leukapheresis collections by Cobe Spectra contained more lymphocytes and platelets than collections by Spectra Optia apheresis machine (median, 9.2 * 10(9) versus 6.7 * 10(9); P = 0.04) and platelets (median, 610 * 10(9) versus 170 * 10(9); P = 0.04). The frequency of CD4(+)CD25(+)FOXP3(+) was significantly higher in the leukapheresis (4.85%; 95% confidence interval, 1.95% to 5.38%) than in peripheral blood (3.9%; 95% confidence interval, 2.63% to 6.45%) (P = 0.02). The CD8- and CD19-negative depletion step was associated with significant loss of total CD4(+) T cells (P = 0.001). CONCLUSIONS: Results suggest that functional CD25(+) products can be isolated with a GMP-ready method, and good recovery can be obtained with the use of an optimized cryopreservation protocol. These data and methods show the potential, possibilities and future work needed to isolate target cell populations in a reproducible, time-efficient and cost-efficient manner for clinical applications. PMID- 26276009 TI - T cells specific for different latent and lytic viral proteins efficiently control Epstein-Barr virus-transformed B cells. AB - BACKGROUND AIMS: Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorders (PTLD) belong to the most dreaded complications of immunosuppression. The efficacy of EBV-specific T-cell transfer for PTLD has been previously shown, yet the optimal choice of EBV-derived antigens inducing polyclonal CD4(+) and CD8(+) T cells that cover a wide range of human leukocyte antigen types and efficiently control PTLD remains unclear. METHODS: A pool of 125 T-cell epitopes from seven latent and nine lytic EBV-derived proteins (EBVmix) and peptide pools of EBNA1, EBNA3c, LMP2a and BZLF1 were used to determine T-cell frequencies and to isolate T cells through the use of the interferon (IFN)-gamma cytokine capture system. We further evaluated the phenotype and functionality of the generated T-cell lines in vitro. RESULTS: EBVmix induced significantly higher T-cell frequencies and allowed selecting more CD4(+)IFN-gamma(+) and CD8(+)IFN-gamma(+) cells than single peptide pools. T cells of all specificities expanded similarly in vitro, recognized cognate antigen, and, to a lower extent, EBV-infected cells, exerted moderate cytotoxicity and showed reduced alloreactivity. However, EBVmix-specific cells most efficiently controlled EBV-infected lymphoblastoid cell lines (LCLs). This control was mainly mediated by EBV-specific CD8(+) cells with an oligoclonal epitope signature covering both latent and lytic viral proteins. Notably, EBV specific CD4(+) cells unable to control LCLs produced significantly less perforin and granzyme B, probably because of limited LCL epitope presentation. CONCLUSIONS: EBVmix induces a broader T-cell response, probably because of its coverage of latent and lytic EBV-derived proteins that may be important to control EBV-transformed B cells and might offer an improvement of T-cell therapies. PMID- 26276011 TI - Reprint of: Preclinical characterization of DUOC-01, a cell therapy product derived from banked umbilical cord blood for use as an adjuvant to umbilical cord blood transplantation for treatment of inherited metabolic diseases. AB - BACKGROUND AIMS: Cord blood (CB) transplantation slows neurodegeneration during certain inherited metabolic diseases. However, the number of donor cells in the brain of patients does not appear to be sufficient to provide benefit until several months after transplant. We developed the cell product DUOC-01 to provide therapeutic effects in the early post-transplant period. METHODS: DUOC-01 cultures initiated from banked CB units were characterized by use of time-lapse photomicroscopy during the 21-day manufacturing process. Antigen expression was measured by means of flow cytometry and immunocytochemistry; transcripts for cytokines and enzymes by quantitative real-time polymerase chain reaction; activities of lysosomal enzymes by direct biochemical analysis; alloreactivity of DUOC-01 and of peripheral blood (PB) mononuclear cells (MNC) to DUOC-01 by mixed lymphocyte culture methods; and cytokine secretion by Bioplex assays. RESULTS: DUOC-01 cultures contained highly active, attached, motile, slowly proliferating cells that expressed common (cluster of differentiation [CD]11b, CD14 and Iba1), M1 type (CD16, inducible nitric oxide synthase), and M2-type (CD163, CD206) macrophage or microglia markers. Activities of 11 disease-relevant lysosomal enzymes in DUOC-01 products were similar to those of normal PB cells. All DUOC-01 products secreted interleukin (IL)-6 and IL-10. Accumulation of transforming growth factor-beta, IL-1beta, interferon-gamma and TNF-alpha in supernatants was variable. IL-12, IL-2, IL-4, IL-5 and IL-13 were not detected at significant concentrations. Galactocerebrosidase, transforming growth factor-beta and IL-10 transcripts were specifically enriched in DUOC-01 relative to CB cells. PB MNCs proliferated and released cytokines in response to DUOC-01. DUOC-01 did not proliferate in response to mismatched MNC. CONCLUSIONS: DUOC-01 has potential as an adjunctive cell therapy to myeloablative CB transplant for treatment of inherited metabolic diseases. PMID- 26276010 TI - Interaction between human mature adipocytes and lymphocytes induces T-cell proliferation. AB - BACKGROUND AIMS: Adipose tissue is a critical organ that plays a major role in energy balance regulation and the immune response through intricate signals. METHODS: We report on the inter-relation between mature adipocytes and lymphocytes in terms of adipocyte-derived T-cell chemo-attractants and adipocyte metabolic effects on lymphocytes. RESULTS: During the culture time, mature adipocytes changed their structural and functional properties into de differentiated cells. Isolated mature adipocytes expressed significantly higher levels of CIITA, major histocompatibility complex II (human leukocyte antigen [HLA]-DR) and costimulatory signal molecule CD80 compared with adipocytes after the de-differentiation process. Moreover, human leukocyte antigen-G, which may prevent the immune responses of mesenchymal stromal cells, was expressed at lower level in mature adipocytes compared with de-differentiated adipocytes. In line with these molecular data, functional results showed different immunoregulatory properties between adipocytes before and after the de-differentiation process. Mature adipocytes stimulated the proliferation of total lymphocytes and immunoselected cell populations CD3+, CD4+ and CD8+ in a direct contact-dependent way that involved the major histocompatibility complex I and II pathways. Moreover, adipocytes secreted potential chemo-attractant factors, but data showed that adipocyte-derived culture medium was not sufficient to activate lymphocyte proliferation, suggesting that a direct contact between adipocytes and immune cells was needed. However, specific mature adipocyte cytokines enhanced lymphocyte proliferation in a mixed lymphocyte reaction. CONCLUSIONS: In conclusion, cross-talk occurs between adipocytes and lymphocytes within adipose tissue involving T-cell chemo-attraction by mature adipocytes. Our findings, together with current observations in the field, provide a rationale to identify adipocyte-lymphocyte cross-talk that instigates adipose inflammation. PMID- 26276012 TI - Density functional theory study of C2F5I synthesis over activated carbon catalyst. AB - Quantum chemistry calculations based on the density functional theory (DFT) are carried out to investigate the reaction mechanism of C2F5I synthesis catalyzed by activated carbon. The possible adsorption configurations of fluorocarbon intermediates are analyzed carefully. Also, the related transition states and reaction pathway are analyzed. According to calculation, firstly, the dehydrofluorination of C2HF5, as the rate-determining step, is catalyzed by the carboxyl acid groups. Secondly, the tetrafluoroethylidene radicals disproportionate on graphite (001) surface instead of rearrangement or dimerization. Next, the fluorine abstractions between fluorocarbon intermediates over graphite (001) surfaces proceed successfully. Finally, the desorbed pentafluoroethyl abstracts iodine atom from molecular iodine spontaneously to afford C2F5I. In adition, our calculations reveal that the carbon deposit in experiment is caused by the fluorine abstraction from fluoroethinyl. The suggested mechanism corresponds with our calculations and available experiments. PMID- 26276013 TI - Brain catecholamine depletion and motor impairment in a Th knock-in mouse with type B tyrosine hydroxylase deficiency. AB - Tyrosine hydroxylase catalyses the hydroxylation of L-tyrosine to l-DOPA, the rate-limiting step in the synthesis of catecholamines. Mutations in the TH gene encoding tyrosine hydroxylase are associated with the autosomal recessive disorder tyrosine hydroxylase deficiency, which manifests phenotypes varying from infantile parkinsonism and DOPA-responsive dystonia, also termed type A, to complex encephalopathy with perinatal onset, termed type B. We generated homozygous Th knock-in mice with the mutation Th-p.R203H, equivalent to the most recurrent human mutation associated with type B tyrosine hydroxylase deficiency (TH-p.R233H), often unresponsive to l-DOPA treatment. The Th knock-in mice showed normal survival and food intake, but hypotension, hypokinesia, reduced motor coordination, wide-based gate and catalepsy. This phenotype was associated with a gradual loss of central catecholamines and the serious manifestations of motor impairment presented diurnal fluctuation but did not improve with standard l-DOPA treatment. The mutant tyrosine hydroxylase enzyme was unstable and exhibited deficient stabilization by catecholamines, leading to decline of brain tyrosine hydroxylase-immunoreactivity in the Th knock-in mice. In fact the substantia nigra presented an almost normal level of mutant tyrosine hydroxylase protein but distinct absence of the enzyme was observed in the striatum, indicating a mutation-associated mislocalization of tyrosine hydroxylase in the nigrostriatal pathway. This hypomorphic mouse model thus provides understanding on pathomechanisms in type B tyrosine hydroxylase deficiency and a platform for the evaluation of novel therapeutics for movement disorders with loss of dopaminergic input to the striatum. PMID- 26276014 TI - Fall Down Detection Under Smart Home System. AB - Medical technology makes an inevitable trend for the elderly population, therefore the intelligent home care is an important direction for science and technology development, in particular, elderly in-home safety management issues become more and more important. In this research, a low of operation algorithm and using the triangular pattern rule are proposed, then can quickly detect fall down movements of humanoid by the installation of a robot with camera vision at home that will be able to judge the fall-down movements of in-home elderly people in real time. In this paper, it will present a preliminary design and experimental results of fall-down movements from body posture that utilizes image pre-processing and three triangular-mass-central points to extract the characteristics. The result shows that the proposed method would adopt some characteristic value and the accuracy can reach up to 90 % for a single character posture. Furthermore the accuracy can be up to 100 % when a continuous-time sampling criterion and support vector machine (SVM) classifier are used. PMID- 26276015 TI - Cloud-Based Smart Health Monitoring System for Automatic Cardiovascular and Fall Risk Assessment in Hypertensive Patients. AB - The aim of this paper is to describe the design and the preliminary validation of a platform developed to collect and automatically analyze biomedical signals for risk assessment of vascular events and falls in hypertensive patients. This m health platform, based on cloud computing, was designed to be flexible, extensible, and transparent, and to provide proactive remote monitoring via data mining functionalities. A retrospective study was conducted to train and test the platform. The developed system was able to predict a future vascular event within the next 12 months with an accuracy rate of 84 % and to identify fallers with an accuracy rate of 72 %. In an ongoing prospective trial, almost all the recruited patients accepted favorably the system with a limited rate of inadherences causing data losses (<20 %). The developed platform supported clinical decision by processing tele-monitored data and providing quick and accurate risk assessment of vascular events and falls. PMID- 26276016 TI - Determination of Fatigue Following Maximal Loaded Treadmill Exercise by Using Wavelet Packet Transform Analysis and MLPNN from MMG-EMG Data Combinations. AB - The muscle fatigue can be expressed as decrease in maximal voluntary force generating capacity of the neuromuscular system as a result of peripheral changes at the level of the muscle, and also failure of the central nervous system to drive the motoneurons adequately. In this study, a muscle fatigue detection method based on frequency spectrum of electromyogram (EMG) and mechanomyogram (MMG) has been presented. The EMG and MMG data were obtained from 31 healthy, recreationally active men at the onset, and following exercise. All participants were performed a maximally exercise session in a motor-driven treadmill by using standard Bruce protocol which is the most widely used test to predict functional capacity. The method used in the present study consists of pre-processing, determination of the energy value based on wavelet packet transform, and classification phases. The results of the study demonstrated that changes in the MMG 176-234 Hz and EMG 254-313 Hz bands are critical to determine for muscle fatigue occurred following maximally exercise session. In conclusion, our study revealed that an algorithm with EMG and MMG combination based on frequency spectrum is more effective for the detection of muscle fatigue than EMG or MMG alone. PMID- 26276017 TI - A Software Development Platform for Wearable Medical Applications. AB - Wearable medical devices have become a leading trend in healthcare industry. Microcontrollers are computers on a chip with sufficient processing power and preferred embedded computing units in those devices. We have developed a software platform specifically for the design of the wearable medical applications with a small code footprint on the microcontrollers. It is supported by the open source real time operating system FreeRTOS and supplemented with a set of standard APIs for the architectural specific hardware interfaces on the microcontrollers for data acquisition and wireless communication. We modified the tick counter routine in FreeRTOS to include a real time soft clock. When combined with the multitasking features in the FreeRTOS, the platform offers the quick development of wearable applications and easy porting of the application code to different microprocessors. Test results have demonstrated that the application software developed using this platform are highly efficient in CPU usage while maintaining a small code foot print to accommodate the limited memory space in microcontrollers. PMID- 26276018 TI - A Type-2 Fuzzy Image Processing Expert System for Diagnosing Brain Tumors. AB - The focus of this paper is diagnosing and differentiating Astrocytomas in MRI scans by developing an interval Type-2 fuzzy automated tumor detection system. This system consists of three modules: working memory, knowledge base, and inference engine. An image processing method with three steps of preprocessing, segmentation and feature extraction, and approximate reasoning is used in inference engine module to enhance the quality of MRI scans, segment them into desired regions, extract the required features, and finally diagnose and differentiate Astrocytomas. However, brain tumors have different characteristics in different planes, so considering one plane of patient's MRI scan may cause inaccurate results. Therefore, in the developed system, several consecutive planes are processed. The performance of this system is evaluated using 95 MRI scans and the results show good improvement in diagnosing and differentiating Astrocytomas. PMID- 26276019 TI - Leveraging Clinical Informatics in the Conduct of Clinical Trials. PMID- 26276020 TI - A qualitative study assessing cardiovascular risk factors: the accumulative stressors influencing societal integration of teenage African immigrants. AB - BACKGROUND: This study examines the nature of disparities in cardiovascular risk by exploring chronic stressors and other cardiovascular risk factors on youth of African descent who are integrating into an industrialized society. METHODS: Qualitative data on cardiovascular risk and acclimation to the dominant society were collected from three groups of key informants: (1) community leaders; (2) youth; and (3) a community advisory group. RESULTS: Youth of Ethiopian descent engaged in the same western diets, computerized social networking, and habits in smoking and alcohol use as did youth from the dominant society. However, informants of Ethiopian descent encountered and witnessed racism, institutional discrimination and evidence of devaluing Ethiopian culture, influencing youths' ability to integrate into the society. CONCLUSION: Immigrant youth of Ethiopian descent face an accumulation of conflicting social support, psychosocial factors, and stressors, including: living in low-income, high-crime areas; encountering pervasive discrimination; acclimating to a new and industrialized culture; and navigating within an often unhospitable society. Contributing to these factors are changes in health behaviors such as adding processed foods and sugary drinks to the diet, increasing heavy alcohol use and substituting screen use for physical activity. The accumulative impact of these factors contributes to the marginalization of youth of Ethiopian descent in the dominant society and perpetuates a cycle of increasing cardiovascular risk. PMID- 26276021 TI - How stress triggers itch: a preliminary study of the mechanism of stress-induced pruritus using fMRI. AB - BACKGROUND: Itch is one of the most prevalent and familiar nociceptions in humans and can result in impaired quality of life. The central processing of itch is known to be important in perceptions of itch and strategies for coping with it, and various triggers have been reported to be associated with patterns of brain activation in pruritus. Stress is known to be an important aggravating factor in itch, but the precise mechanism by which brain activation results in stress induced pruritus remains elusive. METHODS: Using functional magnetic resonance imaging (fMRI), we attempted to evaluate if stress-induced pruritus is associated with the activation of certain areas of the brain. Furthermore, we investigated whether sedating antihistamines are more effective than non-sedating antihistamines in decreasing stress-induced pruritus. Memories of stressful events followed by visual stimuli using a series of pictures depicting fearful and stressful conditions, mixed with neutralizing pictures, were used to evoke pruritus. RESULTS: The hippocampus and subcortical structures were found to be involved in stress-associated pruritus. Interestingly, sedating antihistamines were involved in the deactivation of brain regions associated with the relief of itch by active scratching, which suggests that sedating antihistamines may mitigate pruritus by instigating patterns of brain activity similar to those induced by scratching behavior. CONCLUSIONS: Itch scratching reflects a complicated pattern of brain activity. Activation of the hippocampus appears to be involved in stress-associated pruritus, and sedating antihistamines may work in a manner similar to that of scratching behavior. To our knowledge, this is the first study to evaluate brain functioning in relation to stress-induced pruritus. PMID- 26276022 TI - Mini-Symposium: Emerging Viral Infections of the Central Nervous System. PMID- 26276023 TI - Diagnostics and Discovery in Viral Central Nervous System Infections. AB - The range of viruses implicated in central nervous system disease continues to grow with globalization of travel and trade, emergence and reemergence of zoonoses and investments in discovery science. Diagnosis of viral central nervous system infections is challenging in that brain tissue, where the pathogen concentration is likely to be highest, is not readily obtained and sensitive methods for molecular and serological detection of infection are not available in most clinical microbiology laboratories. Here we review these challenges and discuss how they may be addressed using advances in molecular, proteomic and immunological methods. PMID- 26276024 TI - Henipavirus Encephalitis: Recent Developments and Advances. AB - The genus Henipavirus within the family Paramyxoviridae includes the Hendra virus (HeV) and Nipah virus (NiV) which were discovered in the 1990s in Australia and Malaysia, respectively, after emerging to cause severe and often fatal outbreaks in humans and animals. While HeV is confined to Australia, more recent NiV outbreaks have been reported in Bangladesh, India and the Philippines. The clinical manifestations of both henipaviruses in humans appear similar, with a predominance of an acute encephalitic syndrome. Likewise, the pathological features are similar and characterized by disseminated, multi-organ vasculopathy comprising endothelial infection/ulceration, vasculitis, vasculitis-induced thrombosis/occlusion, parenchymal ischemia/microinfarction, and parenchymal cell infection in the central nervous system (CNS), lung, kidney and other major organs. This unique dual pathogenetic mechanism of vasculitis-induced microinfarction and neuronal infection causes severe tissue damage in the CNS. Both viruses can also cause relapsing encephalitis months and years after the acute infection. Many animal models studied to date have largely confirmed the pathology of henipavirus infection, and provided the means to test new therapeutic agents and vaccines. As the bat is the natural host of henipaviruses and has worldwide distribution, spillover events into human populations are expected to occur in the future. PMID- 26276025 TI - Understanding Enterovirus 71 Neuropathogenesis and Its Impact on Other Neurotropic Enteroviruses. AB - Enterovirus A71 (EV-A71) belongs to the species group A in the Enterovirus genus within the Picornaviridae family. EV-A71 usually causes self-limiting hand, foot and mouth disease or herpangina but rarely causes severe neurological complications such as acute flaccid paralysis and encephalomyelitis. The pathology and neuropathogenesis of these neurological syndromes is beginning to be understood. EV-A71 neurotropism for motor neurons in the spinal cord and brainstem, and other neurons, is mainly responsible for central nervous system damage. This review on the general aspects, recent developments and advances of EV-A71 infection will focus on neuropathogenesis and its implications on other neurotropic enteroviruses, such as poliovirus and the newly emergent Enterovirus D68. With the imminent eradication of poliovirus, EV-A71 is likely to replace it as an important neurotropic enterovirus of worldwide importance. PMID- 26276026 TI - West Nile Virus Encephalitis 16 Years Later. AB - Arboviruses (Arthropod-borne viruses) include several families of viruses (Flaviviridae, Togaviradae, Bunyaviradae, Reoviradae) that are spread by arthropod vectors, most commonly mosquitoes, ticks and sandflies. The RNA genome allows these viruses to rapidly adapt to ever-changing host and environmental conditions. Thus, these virus families are largely responsible for the recent expansion in geographic range of emerging viruses including West Nile virus (WNV), dengue virus and Chikungunya virus. This review will focus on WNV, especially as it has progressively spread westward in North America since its introduction in New York in 1999. By 2003, WNV infections in humans had reached almost all lower 48 contiguous United States (US) and since that time, fluctuations in outbreaks have occurred. Cases decreased between 2008 and 2011, followed by a dramatic flair in 2012, with the epicenter in the Dallas-Fort Worth region of Texas. The 2012 outbreak was associated with an increase in reported neuroinvasive cases. Neuroinvasive disease continues to be a problem particularly in the elderly and immunocompromised populations, although WNV infections also represented the second most frequent cause of pediatric encephalitis in these same years. Neuropathological features in cases from the 2012 epidemic highlight the extent of viral damage that can occur in the CNS. PMID- 26276028 TI - 2 Month-Old Male with Hypotonia. PMID- 26276029 TI - An 11-Year-Old Boy with A Sacral Spinal Mass. PMID- 26276027 TI - Emerging Infections of CNS: Avian Influenza A Virus, Rift Valley Fever Virus and Human Parechovirus. AB - History is replete with emergent pandemic infections that have decimated the human population. Given the shear mass of humans that now crowd the earth, there is every reason to suspect history will repeat itself. We describe three RNA viruses that have recently emerged in the human population to mediate severe neurological disease. These new diseases are results of new mutations in the infectious agents or new exposure pathways to the agents or both. To appreciate their pathogenesis, we summarize the essential virology and immune response to each agent. Infection is described in the context of known host defenses. Once the viruses evade immune defenses and enter central nervous system (CNS) cells, they rapidly co-opt host RNA processing to a cataclysmic extent. It is not clear why the brain is particularly susceptible to RNA viruses; but perhaps because of its tremendous dependence on RNA processing for physiological functioning, classical mechanisms of host defense (eg, interferon disruption of viral replication) are diminished or not available. Effectiveness of immunity, immunization and pharmacological therapies is reviewed to contextualize the scope of the public health challenge. Unfortunately, vaccines that confer protection from systemic disease do not necessarily confer protection for the brain after exposure through unconventional routes. PMID- 26276030 TI - 55-Year-Old Man with Acute Ascending Paraparesis. PMID- 26276031 TI - A 19-Year-Old Male with an Intraventricular Tumor. PMID- 26276033 TI - Legacy of a Chemical Factory Site: Contaminated Groundwater Impacts Stream Macroinvertebrates. AB - Legislative and managing entities of EU member states face a comprehensive task because the chemical and ecological impacts of contaminated sites on surface waters must be assessed. The ecological assessment is further complicated by the low availability or, in some cases, absence of ecotoxicity data for many of the compounds occurring at contaminated sites. We studied the potential impact of a contaminated site, characterised by chlorinated solvents, sulfonamides, and barbiturates, on benthic macroinvertebrates in a receiving stream. Most of these compounds are characterised by low or unknown ecotoxicity, but they are continuously discharged into the stream by way of a long-lasting source generating long-term chronic exposure of the stream biota. Our results show that taxonomical density and diversity of especially sediment dwelling taxa were reduced by >50 % at the sampling sites situated in the primary inflow zone of the contaminated GW. Moreover, macroinvertebrate communities at these sampling sites could be distinguished from those at upstream control sites and sites situated along a downstream dilution gradient using multidimensional scaling. Importantly, macroinvertebrate indices currently used did not identify this impairment, thus underpinning an urgent need for developing suitable tools for the assessment of ecological effects of contaminated sites in streams. PMID- 26276034 TI - Factors Affecting Antioxidant Response in Fish from a Long-term Mercury Contaminated Reservoir. AB - The objective of this work was to evaluate antioxidant defence and oxidative damage in organs (liver, gills, kidney, and brain) of five fish species (Aspius aspius, Esox lucius, Sander lucioperca, Abramis brama, Rutilus rutilus) from the long-term mercury-contaminated Skalka Reservoir in the Czech Republic. Special emphasis was placed on a comprehensive assessment of the factors that may affect the antioxidant response to mercury in fish. Antioxidant enzymes (glutathione reductase, glutathione peroxidase, and glutathione-S-transferase) did not significantly respond to mercury contamination. Levels of the analysed enzymes and oxidative damage to lipids were predominantly determined by a separate organ factor or species factor, or by the combination of both (p < 0.001). Levels of total glutathione and the reduced/oxidized glutathione ratio were influenced by mercury contamination in combination with their specific organ distribution (p < 0.001). Our results suggest that species and type of organ alone or in combination are more important factors than chronic exposure to mercury contamination with respect to effects on antioxidant defence in fish under field conditions. Our findings suggest that the main antioxidant defensive mechanism in fish from the studied long-term mercury contaminated site was the inter-tissue distribution of glutathione. PMID- 26276035 TI - Metformin synergizes 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) combination therapy through impairing intracellular ATP production and DNA repair in breast cancer stem cells. AB - Metformin, an AMPK activator, has been reported to improve pathological response to chemotherapy in diabetic breast cancer patients. To date, its mechanism of action in cancer, especially in cancer stem cells (CSCs) have not been fully elucidated. In this study, we demonstrated that metformin, but not other AMPK activators (e.g. AICAR and A-769662), synergizes 5-fluouracil, epirubicin, and cyclophosphamide (FEC) combination chemotherapy in non-stem breast cancer cells and breast cancer stem cells. We show that this occurs through an AMPK-dependent mechanism in parental breast cancer cell lines. In contrast, the synergistic effects of metformin and FEC occurred in an AMPK-independent mechanism in breast CSCs. Further analyses revealed that metformin accelerated glucose consumption and lactate production more severely in the breast CSCs but the production of intracellular ATP was severely hampered, leading to a severe energy crisis and impairs the ability of CSCs to repair FEC-induced DNA damage. Indeed, addition of extracellular ATP completely abrogated the synergistic effects of metformin on FEC sensitivity in breast CSCs. In conclusion, our results suggest that metformin synergizes FEC sensitivity through distinct mechanism in parental breast cancer cell lines and CSCs, thus providing further evidence for the clinical relevance of metformin for the treatment of cancers. PMID- 26276038 TI - Surgical geriatric oncology: It is time for interventions. PMID- 26276037 TI - TCGA whole-transcriptome sequencing data reveals significantly dysregulated genes and signaling pathways in hepatocellular carcinoma. AB - This study systematically evaluates the TCGA whole-transcriptome sequencing data of hepatocellular carcinoma (HCC) by comparing the global gene expression profiles between tumors and their corresponding nontumorous liver tissue. Based on the differential gene expression analysis, we identified a number of novel dysregulated genes, in addition to those previously reported. Top-listing upregulated (CENPF and FOXM1) and downregulated (CLEC4G, CRHBP, and CLEC1B) genes were successfully validated using qPCR on our cohort of 65 pairs of human HCCs. Further examination for the mechanistic overview by subjecting significantly upregulated and downregulated genes to gene set enrichment analysis showed that different cellular pathways were involved. This study provides useful information on the transcriptomic landscape and molecular mechanism of hepatocarcinogenesis for development of new biomarkers and further in-depth characterization. PMID- 26276039 TI - Everolimus for patients with metastatic renal cell carcinoma refractory to anti VEGF therapy: results of a pooled analysis of non-interventional studies. AB - AIM: To assess the efficacy and safety of everolimus in patients with metastatic renal cell carcinoma (mRCC) who failed one or two anti-VEGF therapies. PATIENTS AND METHODS: Data from four prospective, non-interventional studies conducted in Germany, France, Greece and Austria were pooled for this analysis. Patients with mRCC of any histology (clear cell or non-clear cell) were included. VEGF refractory patients received everolimus 10mg/day until disease progression or unacceptable toxicity. The primary objective was to determine everolimus efficacy as measured by time to progression (TTP; from baseline to progression). RESULTS: The overall population comprised 632 patients; 493 patients received everolimus in the second-line setting. Most patients were of favourable/intermediate MSKCC risk (91%), had clear cell mRCC (89%), and had undergone nephrectomy (89%). Median TTP was 6.3months (95% confidence interval [CI], 5.9-6.8) for the overall population and 6.4months (95% CI, 5.8-6.9) for the second-line everolimus population. Similarly, median progression-free survival was 5.5months (95% CI, 5.0-6.1) for the overall population and 5.8months (95% CI, 5.0-6.4) for second line everolimus population. Best tumour response (n=349) was complete or partial remission in 12% of patients and stable disease in 59% of patients. Overall population median overall survival (OS) was 11.2months (95% CI, 9.0-not reached). Commonly reported adverse events (AEs) (any grade) were stomatitis (25%), anaemia (15%) and asthenia (11%). CONCLUSIONS: Results of this pooled analysis provide evidence of safety and effectiveness of second-line everolimus in routine clinical use and support everolimus as a standard of care for VEGF-refractory patients with mRCC. PMID- 26276040 TI - Techniques to improve the maintenance of a laboratory colony of Nyssomyia neivai (Diptera: Psychodidae). AB - BACKGROUND: The most critical phase in sand fly colonization is the high mortality in the larval instars. In this study, we sought out strategies for improving the colonization of Nyssomyia neivai, one of the vectors of cutaneous leishmaniasis agent in South America. METHODS: A colony of Ny. neivai was established in the laboratory from a field population, and the productivity of adults was evaluated considering carrying capacity, diet for larvae and surface for oviposition. RESULTS: The highest emergency rate of adults was achieved with the fewest couples inside 150 mL rearing chambers on a sterilized diet made of rabbit feces, rabbit food, soil and fish food and with vermiculite as a substrate for oviposition and the development of larvae. CONCLUSION: Our data on Ny. neivai colonization showed that the best adult productivities were achieved with fewer couples inside the rearing chambers; smaller rearing containers of 150 mL (due to less fungi growth); sterilized diet made of rabbit feces, rabbit food, soil and fish food; and vermiculite as the substrate for oviposition and development of larvae. PMID- 26276041 TI - Confirmed dioestrus in pseudopregnant mice using vaginal exfoliative cytology improves embryo transfer implantation rate. AB - Embryo transfer is a commonly performed surgical technique. In mice, protocols typically specify pairing recipient females with vasectomized males to induce a receptive uterine environment for embryo implantation. However, this induced receptive state is not always maintained until implantation occurs. The use of a well-characterized correlation between oestrous state and exfoliative vaginal cytology was therefore evaluated to assess uterine receptivity immediately before embryo transfer. Eight- to 12-week-old virgin female CD1 mice (n = 22) were paired overnight with vasectomized males and successfully mated, indicated by the presence of a vaginal plug. These dams underwent embryo transfer 3 days later with embryos obtained from superovulated 4-week-old F1 (C57BL/6 * CBA) females. Non-invasive vaginal lavage was conducted immediately before transfer. Dams were killed 6 days after transfer and the uterus collected for histological analysis. Embryo implantation rate in mice was 96% when cytological analysis of the lavage samples signified dioestrus (n = 6), whereas the implantation rate was <15% (n = 16) when cytology signified other stages of oestrous. This simple, quick, non invasive measure of receptivity was accurate and easily adopted and, when applied prospectively, will avoid unnecessary surgery and subsequent culling of non suitable recipients, while maximizing the implantation potential of each recipient female. PMID- 26276036 TI - Neurophysiology of Reward-Guided Behavior: Correlates Related to Predictions, Value, Motivation, Errors, Attention, and Action. AB - Many brain areas are activated by the possibility and receipt of reward. Are all of these brain areas reporting the same information about reward? Or are these signals related to other functions that accompany reward-guided learning and decision-making? Through carefully controlled behavioral studies, it has been shown that reward-related activity can represent reward expectations related to future outcomes, errors in those expectations, motivation, and signals related to goal- and habit-driven behaviors. These dissociations have been accomplished by manipulating the predictability of positively and negatively valued events. Here, we review single neuron recordings in behaving animals that have addressed this issue. We describe data showing that several brain areas, including orbitofrontal cortex, anterior cingulate, and basolateral amygdala signal reward prediction. In addition, anterior cingulate, basolateral amygdala, and dopamine neurons also signal errors in reward prediction, but in different ways. For these areas, we will describe how unexpected manipulations of positive and negative value can dissociate signed from unsigned reward prediction errors. All of these signals feed into striatum to modify signals that motivate behavior in ventral striatum and guide responding via associative encoding in dorsolateral striatum. PMID- 26276042 TI - White tea consumption restores sperm quality in prediabetic rats preventing testicular oxidative damage. AB - Prediabetes represents a major risk factor for the development of type 2 diabetes mellitus (T2DM). It encompasses some, but not all, T2DM diagnostic criteria. Prediabetes has been recently associated with altered testicular function and increased testicular oxidative stress (OS). Tea is widely consumed and its anti hyperglycaemic/antioxidant properties are known. This study aimed to evaluate whether white tea (WTEA) consumption by prediabetic rats could prevent testicular OS, preserving sperm quality. For that purpose, WTEA (presenting a high catechin content) was given to 30-day-old streptozotocin-induced prediabetic rats for 2 months. Testicular antioxidant potential and OS were evaluated, as well as sperm parameters, by standard techniques. WTEA consumption improved glucose tolerance and insulin sensitivity in prediabetic rats. Testicular antioxidant potential was increased by WTEA consumption, restoring protein oxidation and lipid peroxidation, although glutathione content and redox state were not altered. WTEA consumption improved sperm concentration and sperm quality (motility, viability and abnormality) was restored. Overall, WTEA consumption improved reproductive health of male prediabetic rats. Based on the study results, WTEA consumption appears to be a natural, economical and effective strategy to counteract the deleterious effects of prediabetes on male reproductive health, but further studies will be needed before a definitive recommendation is made. PMID- 26276043 TI - Unifying theory of adult resting follicle recruitment and fetal oocyte arrest. AB - One of the biggest mysteries of ovarian physiology is what controls the emergence of adult primordial follicles from the resting stage, and their steady depletion over the woman's lifetime. A related mystery is why do early oogonia begin meiosis in the fetus and then suddenly arrest for most of fetal and adult life. If fetal oocyte arrest did not occur after meiotic activation, there would be no oocytes left in the female baby by the time she is born. Similarly, without a steady controlled release in the adult ovary of resting follicles, the adult woman would run out of her eggs prematurely and have an early menopause. Could there be a similarity between what causes fetal oocyte arrest and what causes adult oocyte recruitment? The answer begins with the observation of a sudden massive recruitment of primordial follicles after human ovarian transplantation, and the embryologic discoveries about oocyte activation and the time of differentiation of cortex and medulla. The unifying theory is that ovarian cortical tissue pressure controls both fetal oocyte arrest and adult oocyte recruitment. PMID- 26276044 TI - Low-Grade Fibromyxoid Sarcoma of the Head and Neck: A Clinicopathologic Series and Review of the Literature. AB - Low-grade fibromyxoid sarcoma (LGFMS) is a deceptively bland malignancy with potential for late recurrence and metastasis, which usually occurs in the deep soft tissues of the extremities and trunk. Most LGFMSs harbor a characteristic gene fusion of FUS-CREB3L2, and recently MUC4 immunostaining has been found to be highly sensitive and specific for the diagnosis. We present a dedicated series of head and neck LGFMS, including the first reported laryngeal case, as well as a review of reported head and neck cases. The surgical pathology archives of our three institutions were searched for cases of LGFMS arising within the head and neck, and four cases were identified. The H&E slides were reviewed, and immunohistochemistry were performed for pancytokeratin, p63, p40, EMA, S100 protein, beta-catenin, actin, CD34, and MUC4. The patients were 6, 43, 45, and 73 years old (mean 41.8 years) and included three males and one female. The tumors were located in the posterior cervical spine, facial skin, mandible, and larynx. The tumors were treated with surgical excision, and all four had histologic features typical for LGFMS including alternating myxoid and fibrous areas with prominent curvilinear vasculature. All tumors were MUC4 positive (100%), 2/4 (50%) were p63 positive, 1/4 (25%) showed focal EMA positivity; all 4 were negative for pancytokeratin, p40, S100 protein, beta-catenin, actin, and CD34. LGFMS is a low grade sarcoma that rarely develops in the head and neck. Due to its rarity, a pathologist may not consider LGFMS in the differential diagnosis of spindle cell neoplasms within the head and neck. Immunohistochemical staining is helpful, but stains should be selected carefully to avoid misdiagnosis. PMID- 26276045 TI - Molecular responses of alveolar epithelial A549 cells to chronic exposure to titanium dioxide nanoparticles: A proteomic view. AB - Although the biological effects of titanium dioxide nanoparticles (TiO2-NPs) have been studied for more than two decades, the mechanisms governing their toxicity are still unclear. We applied 2D-gel proteomics analysis on A549 epithelial alveolar cells chronically exposed for 2months to 2.5 or 50MUg/mL of deeply characterized TiO2-NPs, in order to obtain comprehensive molecular responses that may reflect functional outcomes. We show that exposure to TiO2-NPs impacts the abundance of 30 protein species, corresponding to 22 gene products. These proteins are involved in glucose metabolism, trafficking, gene expression, mitochondrial function, proteasome activity and DNA damage response. Besides, our results suggest that p53 pathway is activated, slowing down cell cycle progression and reducing cell proliferation rate. Moreover, we report increased content of chaperones-related proteins, which suggests homeostasis re establishment. Finally, our results highlight that chronic exposure to TiO2-NPs affects the same cellular functions as acute exposure to TiO2-NPs, although lower exposure concentrations and longer exposure times induce more intense cellular response. BIOLOGICAL SIGNIFICANCE: Our results make possible the identification of new mechanisms that explain TiO2-NP toxicity upon long-term, in vitro exposure of A549 cells. It is the first article describing -omics results obtained with this experimental strategy. We show that this long-term exposure modifies the cellular content of proteins involved in functions including mitochondrial activity, intra- and extracellular trafficking, proteasome activity, glucose metabolism, and gene expression. Moreover we observe modification of content of proteins that activate the p53 pathway, which suggest the induction of a DNA damage response. Technically, our results show that exposure of A549 cells to a high concentration of TiO2-NPs leads to the identification of modulations of the same functional categories than exposure to low, more realistic concentrations. Still the intensity differs between these two exposure scenarios. We also show that chronic exposure to TiO2-NPs induces the modulation of cellular functions that have already been reported in the literature as being impacted in acute exposure scenarios. This proves that the exposure protocol in in vitro experiments related to nanoparticle toxicology might be cautiously chosen since inappropriate scenario may lead to inappropriate and/or incomplete conclusions. PMID- 26276046 TI - Novel missense mutation in the GALNS gene in an affected patient with severe form of mucopolysaccharidosis type IVA. AB - Mucopolysaccharidosis type IVA (MPS IVA), also known as Morquio A, is an autosomal recessive disorder characterized by a deficiency of N acetylgalactosamine-6-sulfate sulfatase (GALNS), which causes major skeletal and connective tissue abnormalities and affects multiple organ systems. In this study, one MPS IVA patient with a severe form from consanguine large Iranian family has been investigated. To find a mutation, all of the 14 exons and intron exon junctions of GALNS gene were sequenced. Sequencing results were analyzed using bioinformatic analysis in order to predict probable pathogenic effect of the variant. One novel homozygous missense mutation in exon 5, c.542A>G (p.Y181C), was found in the proband. That was predicted as being probably pathogenic by bioinformatics analysis. Segregation and familial study confirmed this pathogenic mutation. In conclusion, we have identified the novel mutation responsible for MPS IVA in an Iranian patient to assist in the diagnosis, genetic counseling and prenatal diagnosis of the affected families. PMID- 26276047 TI - The calibrator value assignment protocol of the Abbott enzymatic creatinine assay is inadequate for ensuring suitable quality of serum measurements. PMID- 26276048 TI - Salivary uric acid as a noninvasive biomarker for monitoring the efficacy of urate-lowering therapy in a patient with chronic gouty arthropathy. AB - BACKGROUND: Monitoring blood uric acid (UA) is important in all patients on urate lowering therapy so that the selection of the effective drugs and dosage adjustments could be made until the target level is reached. The issue is that frequent needle jabs are unacceptable. Reported mean levels of salivary UA were 185-240 MUmol/l in healthy adults. A linear correlation was demonstrated between UA concentrations in saliva and plasma. We monitored salivary UA instead of plasmatic UA in a patient with gout. METHODS: Allopurinol and benzbromarone were used as the therapeutic drugs. Salivary UA; urinary UA and creatinine; and plasmatic UA, creatinine, kynurenine and tryptophan were measured by HPLC. RESULTS: Salivary UA indicated the efficacy of therapy accurately and conveniently. After eight weeks therapy, the weekly mean levels of salivary UA were reduced and maintained to <300 MUmol/l, which was equivalent to <360 MUmol/l of plasmatic UA according to the salivary UA/plasmatic UA ratio of this patient. CONCLUSION: Measurement of salivary UA is a noninvasive and useful way for monitoring the status of hyperuricemia and the therapeutic efficacy of urate lowering therapy. It has value for the management of hyperuricemia and gout. PMID- 26276049 TI - Deep brain stimulation for depression: Scientific issues and future directions. AB - OBJECTIVE: Deep brain stimulation is an experimental intervention for treatment resistant depression. Open trials have shown a sustained response to chronic stimulation in many subjects. However, two recent randomised, double-blind, placebo-controlled trials failed to replicate these results. This article is a conceptual paper examining potential explanations for these discrepant findings. METHOD: We conducted a systematic review of the published studies obtained from PubMed and PsycINFO. Studies were selected if they directly examined the impact of deep brain stimulation on depressive symptoms. We excluded case reports and papers re-describing the same cohort of patients. We compared them with data from the placebo-controlled trials, available from Clinicaltrials.gov and abstracts of the American Society for Stereotactic and Functional Neurosurgery. We supplemented our investigation by reviewing additional publications by the major groups undertaking deep brain stimulation for mood disorders. RESULTS: We selected 10 open studies reporting on eight cohorts of patients using four different operative targets. All published studies reported positive results. This was not replicated in data available from the randomised, placebo-controlled trials. Many studies reported suicide or suicide attempts in the postoperative period. CONCLUSION: We consider the placebo effect, the pattern of network activation, surgical candidacy and design of a blinded trial including the length of a crossover period. We suggest a greater focus on selecting patients with melancholia. We anticipate that methodological refinements may facilitate further investigation of this technology for intractable depression. We conclude by noting the psychiatric adverse events that have been reported in the literature to date, as these will also influence the design of future trials of deep brain stimulation for depression. PMID- 26276050 TI - Problematic Internet use, reward sensitivity and decision making. PMID- 26276051 TI - Treatment of canine atopic dermatitis: 2015 updated guidelines from the International Committee on Allergic Diseases of Animals (ICADA). AB - BACKGROUND: In 2010, the International Task Force on Canine Atopic Dermatitis (now International Committee on Allergic Diseases of Animals, ICADA) published the first consensus guidelines for the treatment of atopic dermatitis (AD) in dogs. This is the first 5-year minor update of this document. RESULTS: The treatment of acute flares of AD should involve the search for, and then elimination of, the cause of the flares, bathing with mild shampoos, and controlling pruritus and skin lesions with interventions that include topical and/or oral glucocorticoids or oclacitinib. For chronic canine AD, the first steps in management are the identification and avoidance of flare factors, as well as ensuring that there is adequate skin and coat hygiene and care; this might include more frequent bathing and possibly increasing essential fatty acid intake. The medications currently most effective in reducing chronic pruritus and skin lesions are topical and oral glucocorticoids, oral ciclosporin, oral oclacitinib, and, where available, injectable recombinant interferons. Allergen specific immunotherapy and proactive intermittent topical glucocorticoid applications are the only interventions likely to prevent or delay the recurrence of flares of AD. CONCLUSIONS: This first 5-year minor update of the international consensus guidelines for treatment of AD in dogs further establishes that the treatment of this disease is multifaceted, and that interventions should be combined for a proven (or likely) optimal benefit. Importantly, treatment plans are likely to vary between dogs and, for the same dog, between times when the disease is at different stages. PMID- 26276052 TI - Repeated measures of inflammation, blood pressure, and heart rate variability associated with traffic exposures in healthy adults. AB - BACKGROUND: Previous human exposure studies of traffic-related air pollutants have demonstrated adverse health effects in human populations by comparing areas of high and low traffic, but few studies have utilized microenvironmental monitoring of pollutants at multiple traffic locations while looking at a vast array of health endpoints in the same population. We evaluated inflammatory markers, heart rate variability (HRV), blood pressure, exhaled nitric oxide, and lung function in healthy participants after exposures to varying mixtures of traffic pollutants. METHODS: A repeated-measures, crossover study design was used in which 23 healthy, non-smoking adults had clinical cardiopulmonary and systemic inflammatory measurements taken prior to, immediately after, and 24 hours after intermittent walking for two hours in the summer months along three diverse roadways having unique emission characteristics. Measurements of PM2.5, PM10, black carbon (BC), elemental carbon (EC), and organic carbon (OC) were collected. Mixed effect models were used to assess changes in health effects associated with these specific pollutant classes. RESULTS: Minimal associations were observed with lung function measurements and the pollutants measured. Small decreases in BP measurements and rMSSD, and increases in IL-1beta and the low frequency to high frequency ratio measured in HRV, were observed with increasing concentrations of PM2.5 EC. CONCLUSIONS: Small, acute changes in cardiovascular and inflammation-related effects of microenvironmental exposures to traffic related air pollution were observed in a group of healthy young adults. The associations were most profound with the diesel-source EC. PMID- 26276054 TI - The Effects of a Multidisciplinary Care Conference on the Quality and Cost of Care for Lung Cancer Patients. AB - BACKGROUND: A prospective, multidisciplinary care conference (MDC) has been shown to result in measurable benefits for patients with non-small cell lung cancer (NSCLC). However whether a MDC also results in a difference in resource utilization and cost as well as whether these benefits persist across a multiinstitutional system has not been reported. This investigation compared propensity-matched patients with NSCLC whose care was coordinated through a MDC to patients without access to an MDC across a geographically diverse system of hospitals. METHODS: The Premiere database (Premier Inc, Charlotte, NC) for a health system's 70 hospitals was used to identify patients undergoing treatment for NSCLC during a 5-year period. Propensity matching was used to populate an MDC and non-MDC cohort. The two cohorts were compared for the costs of staging and diagnosis as well as the timeliness and quality of care metrics. RESULTS: Between 2008 and 2013, 13,254 patients were propensity matched. Patient demographics and Charlson comorbidity scores were comparable after matching. Significant differences were identified in adherence to national guidelines (p < 0.0001) for staging and treatment (p < 0.0001), timeliness of care (p < 0.0001), and costs (p < 0.0001) between the two groups. CONCLUSIONS: This investigation found that patients with NSCLC realize improved quality and timeliness of care when that care is coordinated through an MDC. The use of an MDC was also associated with a significant reduction in cost. These differences persisted across a geographically diverse set of hospitals, providers, and patients. Prospective MDCs should be considered integral and compulsory for patients with NSCLC. PMID- 26276053 TI - Attitudes and behaviours of maternal health care providers in interactions with clients: a systematic review. AB - BACKGROUND: High maternal mortality and morbidity persist, in large part due to inadequate access to timely and quality health care. Attitudes and behaviours of maternal health care providers (MHCPs) influence health care seeking and quality of care. METHODS: Five electronic databases were searched for studies from January 1990 to December 2014. Included studies report on types or impacts of MHCP attitudes and behaviours towards their clients, or the factors influencing these attitudes and behaviours. Attitudes and behaviours mentioned in relation to HIV infection, and studies of health providers outside the formal health system, such as traditional birth attendants, were excluded. FINDINGS: Of 967 titles and 412 abstracts screened, 125 full-text papers were reviewed and 81 included. Around two-thirds used qualitative methods and over half studied public-sector facilities. Most studies were in Africa (n = 55), followed by Asia and the Pacific (n = 17). Fifty-eight studies covered only negative attitudes or behaviours, with a minority describing positive provider behaviours, such as being caring, respectful, sympathetic and helpful. Negative attitudes and behaviours commonly entailed verbal abuse (n = 45), rudeness such as ignoring or ridiculing patients (n = 35), or neglect (n = 32). Studies also documented physical abuse towards women, absenteeism or unavailability of providers, corruption, lack of regard for privacy, poor communication, unwillingness to accommodate traditional practices, and authoritarian or frightening attitudes. These behaviours were influenced by provider workload, patients' attitudes and behaviours, provider beliefs and prejudices, and feelings of superiority among MHCPs. Overall, negative attitudes and behaviours undermined health care seeking and affected patient well-being. CONCLUSIONS: The review documented a broad range of negative MHCP attitudes and behaviours affecting patient well-being, satisfaction with care and care seeking. Reported negative patient interactions far outweigh positive ones. The nature of the factors which influence health worker attitudes and behaviours suggests that strengthening health systems, and workforce development, including in communication and counselling skills, are important. Greater attention is required to the attitudes and behaviours of MHCPs within efforts to improve maternal health, for the sake of both women and health care providers. PMID- 26276056 TI - Progestins as endocrine disrupters in aquatic ecosystems: Concentrations, effects and risk assessment. AB - In aquatic ecosystems, progesterone (P4) and synthetic progestins (gestagens) originate from excretion by humans and livestock. Synthetic progestins are used for contraception and as P4 for medical treatments as well. Despite significant use, their ecotoxicological implications are poorly understood. Only about 50% of the progestins in use have been analyzed for their environmental occurrence and effects in aquatic organisms. Here we critically summarize concentrations and effects of progestins in aquatic systems. P4 and progestins were mostly detected when analyzed for, and they occurred in the low ng/L range in wastewater and surface water. In animal farm waste and runoff, they reached up to several MUg/L. P4 and synthetic progestins act through progesterone receptors but they also interact with other steroid hormone receptors. They act on the hypothalamus pituitary-gonad axis, lead to oocyte maturation in female and sperm motility in male fish. Additionally, other pathways are affected as well, including the circadian rhythm. Effects of P4, mifepristone and eleven synthetic progestins have been studied in fish and a few compounds in frogs and mussels. Environmental risks may be associated with P4, dydrogesterone and medroxyprogesterone acetate, where transcriptional effects were found at highest environmental levels. Reproductive effects occurred at higher levels. However, norethindrone, levonorgestrel and norgestrel compromised reproduction at environmental (ng/L) concentrations. Thus, some of the progestins are very active endocrine disrupters. This review summarizes the current state of the art and highlights risks for fish. Further research is needed into environmental concentrations and effects of non-investigated progestins, unexplored modes of action, and the activity of mixtures of progestins and other steroids to fully assess their environmental risks. PMID- 26276055 TI - Surgical Treatment of Secondary Tricuspid Regurgitation: Insight Derived From Annulus Sizes and Tethering Distances. AB - BACKGROUND: The main goal of this study was to explore the feasibility of stratifying patients with secondary tricuspid regurgitation (TR) into different risk levels, and to compare the surgical outcomes of patients within different risk levels who underwent different tricuspid valve repair (TVP) approaches. METHODS: One hundred and one patients with left-sided valvular disease underwent either left-sided valvular replacement or repair, and 79 patients underwent concomitant TVP. Depending upon their tricuspid annulus diameter and tethering distances, the patients were assessed using 4 risk levels. The different surgical approaches were used in patients within different risk levels. RESULTS: Among the 101 patients, there were 32 patients within risk level I, 28 within risk level II, 20 within risk level III, 21 within risk level IV. In the first risk level, the patients with untreated tricuspid valves had no or mild TR after surgery. In the second and third risk levels, the patients treated with a modified De Vega procedure had mild TR at follow-up. In the fourth risk level, the patients treated with undersized annuloplasty rings exhibited an improved outcome. CONCLUSIONS: The evaluation of both tricuspid annular diameter and tethering distance may help clinicians to stratify patients with secondary TR into different risk levels as a means of choosing an optimal TVP approach. The application of a modified De Vega procedure or an undersized annuloplasty ring in patients within appropriate risk level could improve the treatment for secondary TR. PMID- 26276057 TI - Identification of the mitochondrially encoded subunit 6 of F1FO ATPase in Trypanosoma brucei. AB - Kinetoplast maxicircle DNA of trypanosomatids encodes eighteen proteins. RNA editing is required to confer translatability to mRNA for twelve of these. Sequence conservation of the predicted hydrophobic polypeptides indicates that they represent functional components of the respiratory chain. Yet, so far only two of those, cytochrome c oxidase subunit I and apocytochrome b of cytochrome c reductase, have been identified with biochemical methods. Here we report on identification of A6 subunit of F1FO ATPase encoded by a pan-edited mRNA in Trypanosoma brucei. The polypeptide was present among the (35)S-labeled mitochondrial translation products characterized by anomalous migration in denaturing 2D gels. It was identified as an ATPase subunit by co-migration with this complex in Blue Native 2D gels. A partial N-terminal sequence of the corresponding polypeptide present in the gel-purified ATPase complex from Leishmania tarentolae was consistent with the predicted A6 sequence. PMID- 26276058 TI - [Prevalence of overweight and childhood obesity in an area of Extremadura]. PMID- 26276059 TI - [Positive health resources: Exploratory study with groups from the Pamplona school area]. PMID- 26276060 TI - [Evaluation of clinical tutors and medical students regarding clinical rotations in primary healthcare centers and hospitals]. PMID- 26276061 TI - Comparison of venoms from wild and long-term captive Bothrops atrox snakes and characterization of Batroxrhagin, the predominant class PIII metalloproteinase from the venom of this species. AB - Comparisons between venoms from snakes kept under captivity or collected at the natural environment are of fundamental importance in order to obtain effective antivenoms to treat human victims of snakebites. In this study, we compared composition and biological activities of Bothrops atrox venom from snakes collected at Tapajos National Forest (Para State, Brazil) or maintained for more than 10 years under captivity at Instituto Butantan herpetarium after have been collected mostly at Maranhao State, Brazil. Venoms from captive or wild snakes were similar except for small quantitative differences detected in peaks correspondent to phospholipases A2 (PLA2), snake venom metalloproteinases (SVMP) class PI and serine proteinases (SVSP), which did not correlate with fibrinolytic and coagulant activities (induced by PI-SVMPs and SVSPs). In both pools, the major toxic component corresponded to PIII-SVMPs, which were isolated and characterized. The characterization by mass spectrometry of both samples identified peptides that matched with a single PIII-SVMP cDNA characterized by transcriptomics, named Batroxrhagin. Sequence alignments show a strong similarity between Batroxrhagin and Jararhagin (96%). Batroxrhagin samples isolated from venoms of wild or captive snakes were not pro-coagulant, but inhibited collagen induced platelet-aggregation, and induced hemorrhage and fibrin lysis with similar doses. Results suggest that in spite of environmental differences, venom variability was detected only among the less abundant components. In opposition, the most abundant toxin, which is a PIII-SVMP related to the key effects of the venom, is structurally conserved in the venoms. This observation is relevant for explaining the efficacy of antivenoms produced with venoms from captive snakes in human accidents inflicted at distinct natural environments. PMID- 26276062 TI - Orthogonal bioorthogonal chemistries. AB - Bioorthogonal reactions have long been used to examine individual biomolecules in living systems. Studies of multi-component networks demand not only reliable bioorthogonal chemistries, but also combinations of reactions that can be used in tandem. Such 'orthogonal bioorthogonal' transformations have been reported in recent years, and these chemistries are enabling new explorations into biology. This article highlights the development of orthogonal bioorthogonal reactions and their application in multi-target imaging and macromolecule assembly. Methods to tune and control orthogonal reactivity are also discussed, along with prospects for identifying new classes of compatible reactions. PMID- 26276063 TI - Complete disappearance of coronary pathology. PMID- 26276064 TI - Porous polyethylene implants in facial reconstruction: Outcome and complications. AB - The aim of the present study was to assess the indications, results and complications of patients treated with porous polyethylene (Medpor((r))) implants in the Department of Oral and Maxillofacial Surgery of VU Medical Centre, Amsterdam over 17 years. A total of 69 high-density porous polyethylene implants (Medpor((r)) Biomaterial; Porex Surgical, Newman, GA) were used in forty patients (22 males, 18 females). All patients were analysed for gender, age, diagnosis, indications for surgery, follow-up period and postoperative complications. A mean age of 34.1 years was observed. The main reason for implant surgery was post traumatic functional impairment (27.5%). Most implants were placed at the mandibular angel and the orbital floor. Unsatisfactory appearance scored the highest in postoperative complications (10.1%) followed by infection rate (7.2%). Comparing the number of implants placed over the years and the incidence of complications, makes the overall complications rate of porous polyethylene very low. A consensus about antibiotic prophylaxis is needed. The objective measurements in patient satisfaction and proper implant design would be of great use. PMID- 26276065 TI - Pretreatment of plasma samples by a novel hollow fiber centrifugal ultrafiltration technique for the determination of plasma protein binding of three coumarins using acetone as protein binding releasing agent. AB - A novel and practical sample pretreatment method based on hollow fiber centrifugal ultrafiltration (HFCF-UF) was developed to determine plasma protein binding by using HPLC. The samples for analyzing unbound and total concentrations could be prepared in parallel simultaneously by the same device. It only required centrifugation for a short time and the filtrate could be injected directly for HPLC analysis without further treatment. Coumarins were selected as the model drugs. Acetone was chosen as the releasing agent to free the binding drug from the drug-protein complex for the total drug concentration determination. Non specific bindings (NSBs) between the analytes and hollow fiber membrane materials were investigated. The type and volume of protein binding releaser were optimized. Additionally, centrifugal speed and centrifugal time were considered. Under the optimized conditions, the absolute recovery rates of the unbound and total concentrations were in the range of 97.5-100.9% for the three analytes. The limits of detection were in the range of 0.0135-0.0667MUgmL(-1). In vitro plasma protein binding of the three coumarins was determined at three concentrations using the validated method and the relative standard deviations (RSDs) were less than 3.4%. Compared with traditional method, the HFCF-UF method is simple to run, no specialized equipment requirement and is a more accurate plasma pretreatment procedure with almost excellent drug-protein binding equilibrium. Therefore, this method can be applied to determine the plasma protein binding in clinical practice. It also provides a reliable alternative for accurate monitoring of unbound or total drug concentration in therapeutic drug monitoring (TDM). PMID- 26276066 TI - Ionic liquid matrix-based dispersive liquid-liquid microextraction for enhanced MALDI-MS analysis of phospholipids in soybean. AB - Ionic liquid matrix (ILM) is found to be a very versatile substance for analysis of broad range of organic molecules in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) due to good solubility for a variety of analytes, formation of homogenous crystals and high vacuum stability of the matrix. In the present work, an ILM, cyno-4-hydroxycinnamic acid butylamine (CHCAB) was employed in dispersive liquid-liquid microextraction (DLLME) as sample probe and matrix for extraction and ionization of phospholipids from food samples (soybean) prior to MALDI-MS analysis. With the employed technique, 8-125 fold improvement in signal intensity and limit of detection were achieved for the analysis of phospholipids. The best extraction efficiency of phospholipids in ILM-DLLME was obtained with 5min extraction time in presence 30mg/mL CHCAB and 1.2% NaCl using chloroform as an extracting solvent and methanol as a dispersing solvent. Further, the developed ILM-DLLME procedure has been successfully applied for the analysis of phospholipids in soybean samples in MALDI-MS. PMID- 26276067 TI - The Impact of the 2009 Special Supplemental Nutrition Program for Women, Infants, and Children Food Package Revisions on Participants: A Systematic Review. AB - For the first time since 1980, the US Department of Agriculture Food and Nutrition Service Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) food package policies were revised in 2009 to meet the Institute of Medicine's nutrition recommendations. These changes included increases in fruits, vegetables, whole grains, and low-fat dairy to improve nutrition and health of WIC participants. Our systematic review of the literature assessed the influence that the 2009 WIC food package revisions have had on dietary intake, healthy food and beverage availability, and breastfeeding participation. The systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Four electronic databases were searched between April 1 and 30, 2014, for peer-reviewed research. Two reviewers screened the articles, extracted the data, and established inter-rater reliability by discussing and resolving discrepancies. Twenty articles were included that met our inclusion criteria. Nine of the studies analyzed changes in dietary intake, eight examined changes in healthy food and beverage availability, and three evaluated breastfeeding participation exclusively. The review demonstrated an improved dietary intake and an increase in the availability of healthier foods and beverages in authorized WIC stores. The revised food package was also associated with improved dietary intake of WIC participants. Mixed results were demonstrated in regard to improved breastfeeding outcomes. Further research is needed to assess the influence of WIC 2009 food package revisions on breastfeeding outcomes and to make conclusions about broad nutrition-related implications. PMID- 26276068 TI - Hospital-based and telemonitoring guided home-based training programs: effects on exercise tolerance and quality of life in patients with heart failure (NYHA class III) and cardiac resynchronization therapy. A randomized, prospective observation. AB - Cardiac resynchronization therapy with defibrillator function (CRT-D) along with an optimal medical therapy improves symptoms, cardiac efficiency, quality of life (QoL) and prognosis in patients with heart failure (CHF). The aim of the study was to assess effects of hospital-based and home-based/telemonitoring exercise training. METHODS: The prospective, randomized study was conducted in 52 patients (pts), aged 45-75years (mean 62+/-9.3), with CHF of ischemic or another etiology, NYHA class III and implanted CRT-D. Group CRT-Ex (n=26) underwent initial exercise training in the hospital setting and continued training program at home with telemonitoring 5 times a week for 8weeks. The CRT-control group (n=26) consisted of patients who had hospital rehabilitation, but no training program after discharge. RESULTS: No differences between the groups in CHF etiology, comorbidities, medical therapy and in any of spiroergometry (CPX) parameters at baseline were observed. After 3-4months the CRT-Ex group achieved better results in VO2 peak, VCO2 peak and treadmill test duration. But after 12months the measurements returned to the baseline values. No significant differences were observed directly between two groups in distances of 6-MWT at baseline, at 3 4months and at 12months. Echocardiographic evaluation showed significant reduction of left ventricular dimensions and improvement in the left ventricular ejection fraction (EF), in both groups (25.3+/-7.4% to 28.9+/-9.1%, CRT-Ex group, p=0.0213 and 24.9+/-7.2% to 31.7+/-10.6%, CRT-Control group, p=0.0001). Significant improvement in all domains of QoL was observed in the CRT-Ex group, while the CRT-Control pts declared only higher energy levels and less pain. Intensity of telemonitoring guided home-based exercise training was low. In the 12- and 18-months follow-up there were no differences in the ICD-interventions, mortality or hospitalization rates between the groups. CONCLUSIONS: A structured exercise training program in the hospital and home-based with telemonitoring was safe option of additional treatment and improved directly physical fitness and, quality of life in patients with NYHA III CHF and CRT-D. However these effects haven't been sustained in longer period of time and had no impact on prognosis. PMID- 26276075 TI - Mechanical thrombectomy with the Trevo ProVue device in ischemic stroke patients: does improved visibility translate into a clinical benefit? AB - PURPOSE: To investigate the efficacy and safety of the Trevo ProVue (TPV) stent retriever in stroke patients with large artery occlusions, with particular attention to the full structural radiopacity of the TPV. MATERIALS AND METHODS: Case files and images of TPV treatments were reviewed for clinical and technical outcome data, including revascularization rates, device and procedure related complications, and outcome at discharge and after 90 days. RESULTS: 76 patients were treated with TPV. Mean National Institutes of Health Stroke Scale (NIHSS) score was 18 and 68% had additional intravenous thrombolysis. 63 occlusions were in the anterior circulation: 44 M1 (58%), 8 M2 (11%), 8 internal carotid artery terminus (11%), 2 internal carotid artery- left (3%), 1 A2 (1%), and 13 vertebrobasilar (17%). 58 of 76 (76%) were solely treated with TPV; the remainder were treated with additional stent retrievers. Mean number of passes in TPV only cases was 2.2 (SD 1.2). In rescue cases, 3.2 (SD 2.2) passes were attempted with the TPV followed by 2.6 rescue device passes (SD 2). TPV related adverse events occurred in 4/76 cases (5%) and procedural events in 6/76 cases (8%). Mean procedural duration was 64 min (SD 42). Thrombolysis in Cerebral Infarction (TICI) 2b/3 recanalization was achieved in 69/76 patients (91%), including 50% TICI 3. Of 56 survivors (74%), 37 (49%) showed a favorable outcome at 90 days (Solitaire With the Intention for Thrombectomy trial criteria), statistically associated with age, baseline NIHSS, onset to revascularization time, and TICI 2b 3 reperfusion. TPV radiopacity allowed for visual feedback, changing the methodology of stent retriever use in 44/76 cases (58%). CONCLUSIONS: Neurothrombectomy with TPV is feasible, effective, and safe. The recanalization rate compares favorably with reported data in the literature. Improved structural radiopacity may facilitate neurothrombectomy or influence the course of action during retrieval. PMID- 26276076 TI - Severe hemiparesis as a prehospital tool to triage stroke severity: a pilot study to assess diagnostic accuracy and treatment times. AB - INTRODUCTION: With the publication of the recent trials showing the tremendous benefits of mechanical thrombectomy, opportunities exist to refine prehospital processes to identify patients with larger stroke syndromes. MATERIALS AND METHODS: We retrospectively reviewed consecutive patients who were brought via scene flight from rural parts of the region to our institution, from December 1, 2014 to June 5, 2015, with severe hemiparesis or hemiplegia. We assessed the accuracy of the diagnosis of stroke and the number of patients requiring endovascular therapy. Moreover, we reviewed the times along the pathway of patients who were treated with endovascular therapy. RESULTS: 45 patients were brought via helicopter from the field to our institution. 27 (60%) patients were diagnosed with an ischemic stroke. Of these, 12 (26.7%) were treated with mechanical thrombectomy and 6 (13.3%) with intravenous tissue plasminogen activator alone. An additional three patients required embolization procedures for either a dural arteriovenous fistula or cerebral aneurysm. Thus a total of 15 (33%) patients received an endovascular procedure and 21/45 (46.7%) received an acute treatment. For patients treated with thrombectomy, the median time from first medical contact to groin puncture was 101 min, with 8 of the 12 patients (66.7%) being discharged to home. CONCLUSIONS: We have presented a pilot study showing that severe hemiparesis or hemiplegia may be a reasonable prehospital tool in recognizing patients requiring endovascular treatment. Patients being identified earlier may be treated faster and potentially improve outcomes. Further prospective controlled studies are required to assess the impact on outcomes and cost effectiveness using this methodology. PMID- 26276077 TI - The efficacy and risks of preoperative embolization of spinal tumors. AB - BACKGROUND: The goal of preoperative embolization of spinal tumors is to improve surgical outcomes by diminishing the vascular supply to the tumor to reduce intraoperative blood loss and operative time. OBJECTIVE: To report our institutional experience with spinal tumor embolization and review the present literature. METHODS: Clinical records from January 1, 2001 to December 31, 2012 were reviewed and analyzed. Angiograms were used to calculate the percentage reduction in tumor vascularity, and relevant clinical and operative data were collected and analyzed. RESULTS: Thirty-seven patients underwent preoperative spinal tumor embolization (24 metastatic and 13 primary lesions) and were included in the study. One complication resulted in transient lower extremity weakness and was attributed to post-embolization swelling, which fully resolved after surgical resection. The transient neurological complication rate was 1/37 (3%) and the permanent rate was 0/37 (0%). The average surgical estimated blood loss (EBL) was 1946 mL (100-7000 mL) and the average operative time was 330 min (range 164-841 min). After embolization, tumor blush was reduced by 83% on average. Average pre- and postoperative modified Rankin Scale scores were 2.10 and 1.36, respectively (p=0.03). Cases in which tumor blush was decreased by >=90% (classes 1 or 2) after embolization had significantly less operative blood loss than those cases in which <90% (classes 3 or 4) was achieved (mean EBL 1391 vs 2296 mL, respectively, p=0.05). CONCLUSIONS: Spinal tumor embolization is a safe procedure, is associated with few complications, and may improve surgical outcomes by limiting intraoperative blood loss and reducing operative time. PMID- 26276078 TI - Quantitative analysis of hemorrhage clearance and delayed cerebral ischemia after subarachnoid hemorrhage. AB - OBJECTIVE: Initial hemorrhage burden is an independent predictor for delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, the association between clot clearance and DCI still remains to be elucidated. METHODS: Quantitative analysis of hemorrhage volume and clot clearance was made in 116 consecutive patients who were scanned within 24 h from onset. Cisternal plus intraventricular hemorrhage volume (CIHV) was calculated as clot volume from the initial scans and scans performed up to 7 days after onset. Clot clearance was calculated as a percentage of residual clot volume compared with the clot volume on the initial scan. Initial clot volume and clot clearance were dichotomized to evaluate the association with DCI. RESULTS: Included patients were aged 55.5+/-15.2 years with a female preponderance (65.5%, (76/116)). The group with higher initial clot volume (>=17.2 mL) had higher odds for DCI (OR 4.3, 95% CI 1.3 to 14.0, p=0.015). However, the rate of DCI was not different between high and low clot clearance groups (26.7% vs 31.0%, p=0.66). Clot clearance rate was similar in patients with and without DCI up to day 7 after onset. CONCLUSIONS: The quantitative clot clearance rate is not an independent predictor for DCI. PMID- 26276079 TI - Catheter insertion site plasmacytoma. PMID- 26276080 TI - Pyrroloquinoline quinone-conferred neuroprotection in rotenone models of Parkinson's disease. AB - Pyrroloquinoline quinone (PQQ), a redox cofactor in the mitochondrial respiratory chain, has proven to protect neurons against glutamate-induced damage both in vitro and in vivo. This study was aimed to investigate the possible neuroprotective effects of PQQ in rotenone-induced Parkinson's disease (PD) model. Pre-treatment with PQQ prevented cultured SH-SY5Y cells from rotenone induced apoptosis, accompanied by modulation of apoptosis-related proteins (Bcl 2, Bax and Smac), restoration of the mitochondrial membrane potential, inhibition of intracellular reactive oxygen species (ROS) production, suppression of tyrosine residues nitration, and dopamine redistribution. PQQ also exerted protective effects in an in vivo PD model, which was created by rotenone injection into the medial forebrain bundle of rats. Co-injection with PQQ and rotenone improved the apomorphine-evoked rotation, decreased neuronal loss, increased the ROS-scavenging ability, regulated intracellular expressions of mitochondrial complex subunits (Ndufs1-4), tyrosine hydroxylase, and vesicular monoamine transporter 2. Taken together, our results collectively suggest that PQQ confers neuroprotection in rotenone-induced PD model probably through complex and multifaceted mechanisms, at least involving oxidative stress, mitochondrial integrity, and dopamine functions. PMID- 26276081 TI - Paternal BPA exposure in early life alters Igf2 epigenetic status in sperm and induces pancreatic impairment in rat offspring. AB - Exposure to endocrine disruptors in utero appears to alter epigenetics in the male germ-line and subsequently promote adult-onset disease in subsequent generations. Fetal exposure to bisphenol A (BPA), a highly prevalent endocrine disruptor in environment, has been shown to alter epigenetic modification and result in glucose intolerance in adulthood. However, whether fetal exposure to BPA can induce epigenetic modification and phenotypic changes in their subsequent offspring are still unclear. The present study was designed to investigate whether exposure to BPA in early life induced glucose intolerance in the offspring through male germ line, and the underlying epigenetic molecular basis. F0 pregnant SD rats were received corn oil or 40 MUg/kg/day of BPA during gestation and lactation. F1 male rats were maintained to generate F2 offspring by mating with untreated female rats. Both the F1 rats after weaning and the F2 offspring were not received any other treatments. Our results showed that male F2 offspring in the BPA group exhibited glucose intolerance and beta-cell dysfunction. Decreased expression of Igf2 and associated hypermethylation of Igf2 were observed in islets of male F2 offspring. In addition, similar effects were observed in female F2 animals, but the effects were more pronounced in males. Moreover, abnormal expression and methylation of Igf2 was observed in sperm of adult F1 male rats, indicating that epigenetic modification in germ cells can be partly progressed to the next generation. Overall, our study suggests that BPA exposure during early life can result in generational transmission of glucose intolerance and beta-cell dysfunction in the offspring through male germ line, which is associated with hypermethylation of Igf2 in islets. The changes of epigenetics in germ cells may contribute to this generational transmission. PMID- 26276082 TI - Molecular hydrogen attenuates hypoxia/reoxygenation injury of intrahepatic cholangiocytes by activating Nrf2 expression. AB - Hypoxia/reoxygenation (H/R) injury of cholangiocytes causes serious biliary complications during hepatobiliary surgeries. Molecular hydrogen (H2) has been shown to be effective in protecting various cells and organs against oxidative stress injury. Human liver cholangiocytes were used to determine the potential protective effects of hydrogen against cholangiocyte H/R injury and explore the underlying mechanisms. We found that H2 ameliorated H/R-induced cholangiocytes apoptosis. Our study revealed that H2 activated NF-E2-related factor 2 (Nrf2) and downstream cytoprotective protein expression. However, the protective function of H2 was abolished when Nrf2 was silenced. Apoptosis in cholangiocytes isolated from a rat model of liver ischemia/reperfusion injury indicated that H2 significantly attenuates ischemia/reperfusion cholangiocyte injury in vivo. In conclusion, our study shows that H2 protects intrahepatic cholangiocytes from hypoxia/reoxygenation-induced apoptosis in vitro or in vivo, and this phenomenon may depend on activating Nrf2 expression. PMID- 26276083 TI - Toxicokinetics of lefetamine and derived diphenylethylamine designer drugs Contribution of human cytochrome P450 isozymes to their main phase I metabolic steps. AB - Lefetamine was first marketed in the 1940s as an opioid analgesic. Since withdrawal symptoms were observed during treatment, it became a controlled substance. Its N-ethyl and N-iso-propyl derivatives appeared on the illicit drug market in 2008. Metabolism studies for lefetamine and these derivatives showed that N-dealkylation was the initial step for all three substances in rats. The involvement of the ten most important human cytochrome P450 (CYP) isozymes in this N-dealkylation should be studied now. Studies showed the involvement of CYP1A2, CYP2B6, CYP2C19, and CYP3A4 in N-dealkylation of all three compounds and additionally CYP2D6 for lefetamine and NEDPA. All kinetic profiles followed classic Michaelis-Menten kinetics. Using the relative activity factor approach, the following net clearances were calculated: for lefetamine 8% by CYP1A2, 72% by CYP2B6, 2% by CYP2C19, 1% by CYP2D6, and 17% by CYP3A4; for NEDPA 27% by CYP1A2, 30% by CYP2B6, 23% by CYP2C19, 4% by CYP2D6, and 17% by CYP3A4; for NPDPA 18% by CYP1A2, 24% by CYP2B6, 28% by CYP2C19, and 30% by CYP3A4. In addition, calculated data were compared to chemical inhibition studies in human liver microsomes. Due to the involvement of at least four enzymes in the initial metabolic steps, the risk of CYP-related drug-drug or drug-food interactions should be low. PMID- 26276084 TI - Deficiency in adiponectin exaggerates cigarette smoking exposure-induced cardiac contractile dysfunction: Role of autophagy. AB - Second hand smoke is an independent risk factor for cardiovascular disease. Adiponectin (APN), an adipose-derived adipokine, has been shown to offer cardioprotective effect through an AMPK-dependent manner. This study was designed to evaluate the impact of adiponectin deficiency on second hand smoke-induced cardiac pathology and underlying mechanisms using a mouse model of side-stream smoke exposure. Adult wild-type (WT) and adiponectin knockout (APNKO) mice were placed in a chamber exposed to cigarette smoke for 1 hour daily for 40 days. Echocardiographic, cardiomyocyte function, and intracellular Ca2+ handling were evaluated. Autophagy and apoptosis were examined using western blot. 2',7' dichlorodihydrofluorescein diacetate (H2DCFDA) staining was used to evaluate reactive oxygen species (ROS) generation. Masson trichrome staining was employed to measure interstitial fibrosis. Our data revealed that adiponectin deficiency provoked smoke exposure-induced cardiomyopathy (compromised fractional shortening, disrupted cardiomyocyte function and intracellular Ca2+ homeostasis, apoptosis and ROS generation). In addition, these detrimental effects of side stream smoke were accompanied by defective autophagolysosome formation, the effect of which was exacerbated by adiponectin deficiency. Blocking autophagolysosome formation using bafilomycin A1 (BafA1) negated the cardioprotective effect of rapamycin against smoke extract. Induction of autophagy using rapamycin and AMPKalpha activation using AICAR rescued against smoke extract-induced myopathic anomalies in APNKO mice. Our data suggest that adiponectin serves as an indispensable cardioprotective factor against side stream smoke exposure-induced myopathic changes possibly through facilitating autophagolysosome formation. PMID- 26276085 TI - Cardiac effects of long-term active immunization with the second extracellular loop of human beta1- and/or beta3-adrenoceptors in Lewis rats. AB - beta1- and beta3-adrenoceptor (AR) auto-antibodies were detected in patients with dilated cardiomyopathy. Many studies have shown that beta1-AR auto-antibodies with partial agonist-like effect play an important role in the pathogenesis of this disease. Moreover, a recent study carried out in our laboratory has shown that beta3-AR antibodies (beta3-ABs), produced in rats, were able to reduce cardiomyocyte contractility via beta3-AR activation. The aims of this study were (1) to investigate, in isolated cardiomyocytes from rabbit, the role of Gi proteins in the beta3-ABs-induced cardiac negative inotropy, (2) to determine whether beta3-ABs may exhibit beta3-AR antagonistic property which is characteristic of partial agonists, and (3) to determine whether long-term active immunization producing both beta1-ABs and/or beta3-ABs leads to the development of cardiac dysfunction in Lewis rats. Lewis rats were immunized for 6 months with peptidic sequences corresponding to the second extracellular loop of human beta3 AR and/or beta1-AR. Agonistic effect of beta3-ABs was evaluated on electrically field-stimulated isolated cardiomyocytes from adult rabbit by measuring the cell shortening. Echocardiography and ex vivo isolated perfused heart studies were conducted on immunized rats. Finally, beta-AR expression was quantified by immunofluorescence and RT-qPCR. SR58611A (10 nM), a preferential beta3-AR agonist, and purified beta3-ABs (25 MUg/ml) induced a decrease in cell shortening (-39.71+/-4.9% (n=10) and -17.06+/-3.9% (n=10) respectively). This effect was significantly inhibited when the cardiomyocytes were preincubated with pertussis toxin (0.3 MUg/ml), a Gi protein inhibitor (p<0.05). In addition, SR58611A mediated negative inotropic effect was decreased when cardiomyocytes were preincubated with beta3-ABs (p<0.0001). Echocardiography revealed a decrease in the fractional shortening and ejection fraction in rats immunized against beta1 AR and both beta1- and beta3-AR. However, the study on isolated heart showed a decrease of the isoproterenol-induced lusitropic and inotropic effects in the 3 groups of immunized rats. These systolic and diastolic dysfunctions are correlated with a decrease in the expression of beta1-ARs and an increase of beta3-ARs in rats immunized against the beta1-AR and an increase of both beta3-AR and beta1-AR in rats immunized against the beta3-AR. For the first time, these results showed that beta3-ABs had a beta3-AR partial agonist-like activity which might play a role in the pathogenesis of cardiac dysfunction. PMID- 26276086 TI - Mitochondrial ROS and cancer drug resistance: Implications for therapy. AB - Under physiological conditions, a well-coordinated and balanced redox system exists to ensure that reactive oxygen species (ROS) are appropriately utilized to accomplish specific functions, such as signaling and protein regulation. The influence of ROS within malignant cells, whether for good or bad may depend on several factors, such as tumor and tissue type, disease stage, treatment strategy, as well as duration, specificity and levels of ROS. What then are the known roles of ROS in cancer? Firstly, ROS significantly impacts cancer phenotypes. Secondly, the oxidative ROS property responsible for killing cancer cells, also impact secondary signaling networks. Thirdly, a strong correlation exist between ROS and genetic instability which may promote mutations. Finally, emerging observations suggest a role for mitochondrial ROS in cancer drug resistance, with implications for therapy. The mitochondria is a key regulator of metabolic-redox (meta-redox) alterations within cancer cells. Like a double-edged sword, mitochondrial ROS perturbations in cancer therapy may be beneficial or detrimental. However, harnessing ROS-specific cancer-targeting benefits remain a major challenge. PMID- 26276088 TI - Testis follicles ultrastructure of three species of terrestrial isopods (Crustacea, Isopoda Oniscidea). AB - The aim of the research, carried out on three species of terrestrial isopods - Armadillidium granulatum, Halophiloscia hirsuta and Trichoniscus alexandrae - is to bring a first consistent contribution to the knowledge of the ultrastructural organization of the testis follicles. The testis follicles are seat of a remarkable dynamic activity of their cell components (somatic cells and germ cells) that results in a continuous variation, related to the trend of spermatogenesis, of their morphology, organization and of the relationships between the two cell populations. The somatic cells, known in literature as follicular cells, nurse cells or Sertoli cells, are arranged at the periphery of the follicle to form an epithelial layer of variable thickness resting on a thin basal lamina in turn surrounded by a discontinuous network of muscle cells. In A. granulatum and H. hirsuta, two types of Sertoli cells are present: a first type, the nurse cells, envelop the spermatids in cavities within their cytoplasm and through their secretion activity play a fundamental role in the formation of the spermatophores; moreover, they phagocytizes the residual cytoplasm of spermatids. A second type of Sertoli cells shows features that leave clearly identify its supporting role to the spermatophores in formation. In T. alexandrae, instead, only one type of Sertoli cells, the nurse cell, is present, whose features are widely superimposable to those observed in the other two species. Moreover, two septa of Sertoli cells depart from the periphery of the testis follicle to constitute an articulated compartmentalization of the follicle itself, probably targeted to realize at its inside a series of microenvironments functionally diversified in order to meets the needs of the different stages of the spermatogenic cycle. PMID- 26276087 TI - Sympathetic arousal increases a negative memory bias in young women with low sex hormone levels. AB - Emotionally arousing events are typically better attended to and remembered than neutral ones. Current theories propose that arousal-induced increases in norepinephrine during encoding bias attention and memory in favor of affectively salient stimuli. Here, we tested this hypothesis by manipulating levels of physiological arousal prior to encoding and examining how it influenced memory for emotionally salient images, particularly those that are negative rather than positive in valence. We also tested whether sex steroid hormones interact with noradrenergic activity to influence these emotional memory biases in women. Healthy naturally cycling women and women on hormonal contraception completed one of the following physiological arousal manipulations prior to viewing a series of negative, positive and neutral images: (1) immediate handgrip arousal-isometric handgrip immediately prior to encoding, (2) residual handgrip arousal-isometric handgrip 15min prior to encoding, or (3) no handgrip. Sympathetic arousal was measured throughout the session via pupil diameter changes. Levels of 17beta estradiol and progesterone were measured via salivary samples. Memory performance was assessed approximately 10min after encoding using a surprise free recall test. The results indicated that handgrip successfully increased sympathetic arousal compared to the control task. Under immediate handgrip arousal, women showed enhanced memory for negative images over positive images; this pattern was not observed in women assigned to the residual and no-handgrip arousal conditions. Additionally, under immediate handgrip arousal, both high estradiol and progesterone levels attenuated the memory bias for negative over positive images. Follow-up hierarchical linear models revealed consistent effects when accounting for trial-by-trial variability in normative International Affective Picture System valence and arousal ratings. These findings suggest that heightened sympathetic arousal interacts with estradiol and progesterone levels during encoding to increase the mnemonic advantage of negative over positive emotional material. PMID- 26276089 TI - Effect of metformin and adriamycin on transplantable tumor model. AB - Adriamycin is a cytotoxic anthracycline antibiotic used in treatment of many types of cancer. Metformin is antidiabetic drug and is under investigation for treatment of cancer. The aim of this work was to study the effect of each of adriamycin and metformin alone and in combination on solid Ehrlich carcinoma (SEC) in mice. Eighty BALB/C mice were divided into four equal groups: SEC group, SEC+adriamycin, SEC+metformin, SEC+adriamycin+metformin. Tumor volume, survival rate, tissue catalase, tissue reduced glutathione, tissue malondialdehyde, tissue sphingosine kinase 1 activity, tissue caspase 3 activity and tissue tumor necrosis factor alpha were determined. A part of the tumor was examined for histopathological and immunohistochemical study. Adriamycin or metformin alone or in combination induced significant increase in the survival rate, tissue catalase, reduced glutathione and tissue caspase 3 activity with significant decrease in tumor volume, tissue malondialdehyde, tissue sphingosine kinase 1 activity and tumor necrosis factor alpha and alleviated the histopathological changes with significant increase in Trp53 expression and apoptotic index compared to SEC group. In conclusion, the combination of adriamycin and metformin had a better effect than each of these drugs alone against transplantable tumor model in mice. PMID- 26276090 TI - Bone marrow niche in the myelodysplastic syndromes. AB - The myelodysplastic syndromes (MDS) are a diverse group of clonal hematopoietic malignancies characterized by ineffective hematopoiesis, progressive bone marrow (BM) failure, cytogenetic and molecular abnormalities, and variable risk of progression to acute myeloid leukemia (AML). The BM microenvironment in MDS plays an important role in the development of this disorder. The BM stromal cells of MDS patients often harbor distinct chromosomal aberrations than the hematopoietic elements, suggesting different genetic origins. Perturbed cytokine secretions from BM stromal cells such as multipotent mesenchymal stem cells (MSCs) and endothelial cells are associated with increased proliferation and survival of malignant hematopoietic cells. Within the MDS BM there are also alterations in stromal cell composition, signaling and angiogenesis between Low- and High-risk MDS patients. Several open lines of investigation into the MDS niche remain, including the timing of stromal defects in context to dysplastic hematopoiesis. Another important, unanswered question is the impact of age on BM stroma function and regulation (or dysregulation) or hematopoietic stem/progenitor cells. With a better understanding of the MDS niche, new therapeutic strategies will emerge. PMID- 26276091 TI - COX-2 gene promoter DNA methylation status in eutopic and ectopic endometrium of Egyptian women with endometriosis. AB - The pathophysiology of COX-2 expression in endometriosis is a matter of debate. The aim was to investigate the role of DNA methylation of the NF-IL6 site within the promoter of COX-2 gene in the pathogenesis of endometriosis. The endometrial tissues (ectopic and eutopic) were collected from 60 women with endometriosis and 30 women without endometriosis (control group). The methylation status of COX-2 was examined by methylation-specific PCR. Quantitative real-time PCR (RT-PCR) was performed to measure COX-2 mRNA levels in endometrial tissues. We found significantly higher levels of COX-2 in ectopic endometriotic tissue compared with eutopic tissue. Also, we found that the frequencies of methylation status of the NF-IL6 site within the COX-2 promoter in the eutopic and ectopic endometrial tissues of endometriosis groups were significantly decreased in comparison to controls (P=0.002, P=0.000 respectively). Our study demonstrated that DNA hypomethylation of the NF-IL6 site within the promoter of COX-2 gene could be a key mechanism for its elevated expression in the eutopic and ectopic tissues of endometriosis. PMID- 26276092 TI - Patient-Centered Outcomes and Revision Rate in Patients Undergoing ACL Reconstruction Using Bone-Patellar Tendon-Bone Autograft Compared With Bone Patellar Tendon-Bone Allograft: A Matched Case-Control Study. AB - PURPOSE: To determine whether outcomes after ACL reconstruction with bone patellar tendon-bone (BPTB) autograft are similar to those of BPTB allograft, while controlling for graft, surgical technique, and surgeon. METHODS: This study was approved by the institutional review board at The Vail Valley Medical Center in Vail, Colorado. Patients 18 to 70 years old who underwent primary ACL reconstruction were included. Patients in each group were matched by age and gender. Patient demographic data, surgical data, and subjective data were collected prospectively. Subjective questionnaires were administered at a minimum of 2 years after ACL reconstruction. RESULTS: This study included 192 knees (191 patients; 143 male, 48 female; mean age, 33 years; range, 18 to 57 years), with 96 knees in each group. No autografts required ACL revision. The revision rate for allograft group was 14% (n = 11; mean age, 23 years; range, 18 to 40 years). Of 11 revisions, 9 (82%) were <=25 years old. In allograft group, patients <=25 years old were 23 times (95% confidence interval, 4.4 to 123.0) more likely to require revision ACL reconstruction than patients >25 years (P < .001). Follow-up was available for 87% of patients (n = 156/180). Mean follow-up time in the allograft group was 4.7 years (range, 2.0 to 9.8 years), and in the autograft group, 8.6 years (range, 2.0 to 16.2 years; P < .001). There was no significant difference between allografts and autografts for mean Lysholm (85.6 v 83.4; P = .43), mean Tegner (6.0 v 5.4; P = .09), or mean patient satisfaction (9.0 v 8.8; P = .57). Lysholm score correlated to Tegner (rho = 0.404; P < .001) and patient satisfaction with outcome (rho = 0.443; P <= .001). Tegner was correlated with age at surgery (rho = -0.274; P < .001). CONCLUSIONS: There was no significant difference in patient-centered outcomes based on graft type; however, the allograft group required more revisions. Patient satisfaction was high for both groups. ACL reconstruction using BPTB autograft or allograft produces similar outcomes; however, revision rates were higher for allografts. LEVEL OF EVIDENCE: Level III, retrospective comparative study. PMID- 26276093 TI - Increased Failure Rates After Anterior Cruciate Ligament Reconstruction With Soft Tissue Autograft-Allograft Hybrid Grafts. AB - PURPOSE: To compare the rate of failure between a group of patients who underwent anterior cruciate ligament (ACL) reconstruction with an autograft-allograft hybrid soft-tissue graft and a matched group of patients who underwent ACL reconstruction with hamstring autograft. METHODS: From 2007 to 2012, 29 patients underwent hybrid ACL reconstruction performed by 4 fellowship-trained sports medicine surgeons at a single institution. Patients who underwent ACL reconstruction with hamstring autograft comprised the control group and were matched to patients in the hybrid group by sex, age, date of surgery, reconstruction technique, and method of femoral fixation. Graft failure was defined as revision ACL reconstruction or complete graft rupture on magnetic resonance imaging. Graft compromise was defined as magnetic resonance imaging evidence of partial graft rupture or arthroscopically identified partial graft rupture. Lysholm Knee Scoring Scale and International Knee Documentation Committee scores were obtained. RESULTS: Both groups included 10 men and 19 women, with a mean postoperative follow-up period of 44.4 +/- 16.9 months in the hybrid group and 48.0 +/- 15.2 months in the control group. Follow-up was obtained in 25 of 29 patients (86.2%) in the hybrid group, and each was matched to 1 patient who received hamstring autograft. The failure rate was 13.8% (4 of 29 patients) in the hybrid group compared with 3.4% (1 of 29) in the control group (P = .160). An additional 27.6% of hybrid group patients (7 of 29) had compromised grafts as defined earlier, as compared with 1 (3.4%) of the control patients (P = .022). Thus the overall hybrid graft failure/compromise rate was 37.9% (11 of 29) compared with 6.9% (2 of 29) for the hamstring autograft group (P = .005). In the hybrid group, the Lysholm score (80.2 +/- 12.1) was significantly lower than that in the control autograft ACL group (89.9 +/- 11.8) (P = .030). The International Knee Documentation Committee score for the hybrid ACL group (71.26 +/- 19.5) was significantly worse than that for the autograft ACL group (85.7 +/- 13.0) (P = .012). CONCLUSIONS: Allograft-autograft hybrid hamstring ACL grafts fail or become structurally compromised at a higher rate than matched autograft hamstring controls. LEVEL OF EVIDENCE: Level III, retrospective comparative study. PMID- 26276094 TI - Techno-economic feasibility and life cycle assessment of dairy effluent to renewable diesel via hydrothermal liquefaction. AB - The economic feasibility and environmental impact is investigated for the conversion of agricultural waste, delactosed whey permeate, through yeast fermentation to a renewable diesel via hydrothermal liquefaction. Process feasibility was demonstrated at laboratory-scale with data leveraged to validate systems models used to perform industrial-scale economic and environmental impact analyses. Results show a minimum fuel selling price of $4.78 per gallon of renewable diesel, a net energy ratio of 0.81, and greenhouse gas emissions of 30.0g-CO2-eqMJ(-1). High production costs and greenhouse gas emissions can be attributed to operational temperatures and durations of both fermentation and hydrothermal liquefaction. However, high lipid yields of the yeast counter these operational demands, resulting in a favorable net energy ratio. Results are presented on the optimization of the process based on economy of scale and a sensitivity analysis highlights improvements in conversion efficiency, yeast biomass productivity and hydrotreating efficiency can dramatically improve commercial feasibility. PMID- 26276095 TI - Determination of kinetic parameters of Phlomis bovei de Noe using thermogravimetric analysis. AB - This paper reports the pyrolysis study of Phlomis bovei biomass by thermogravimetric experiments in order to determine the thermal degradation behavior and kinetic parameters. The weight losses were found to occur in three stages. In the DTG thermograms, an increase of the heating rate tended to delay thermal degradation processes towards higher temperatures. The average values of activation energy and pre-exponential factor calculated from Ozawa-Flynn-Wall, Kissinger-Akahira-Sunose and Kissinger methods are 134.83, 134.06, 223.31kJ/mol and 4.1610(13), 1.1810(10), 2.8110(11)/s, respectively. The three-pseudo component method shows that the activation energy increases with increasing the heating rate for hemicellulose and cellulose while the activation energy of the lignin decreased with an increase of the heating rate. Predicted results and experimental data exhibit similar tendencies and the three pseudo-components model with n different from unity 1 is recommended as the most suitable for prediction of kinetic behavior of Phlomis bovei de Noe. PMID- 26276096 TI - Arthropod eyes: The early Cambrian fossil record and divergent evolution of visual systems. AB - Four types of eyes serve the visual neuropils of extant arthropods: compound retinas composed of adjacent facets; a visual surface populated by spaced eyelets; a smooth transparent cuticle providing inwardly directed lens cylinders; and single-lens eyes. The first type is a characteristic of pancrustaceans, the eyes of which comprise lenses arranged as hexagonal or rectilinear arrays, each lens crowning 8-9 photoreceptor neurons. Except for Scutigeromorpha, the second type typifies Myriapoda whose relatively large eyelets surmount numerous photoreceptive rhabdoms stacked together as tiers. Scutigeromorph eyes are facetted, each lens crowning some dozen photoreceptor neurons of a modified apposition-type eye. Extant chelicerate eyes are single-lensed except in xiphosurans, whose lateral eyes comprise a cuticle with a smooth outer surface and an inner one providing regular arrays of lens cylinders. This account discusses whether these disparate eye types speak for or against divergence from one ancestral eye type. Previous considerations of eye evolution, focusing on the eyes of trilobites and on facet proliferation in xiphosurans and myriapods, have proposed that the mode of development of eyes in those taxa is distinct from that of pancrustaceans and is the plesiomorphic condition from which facetted eyes have evolved. But the recent discovery of enormous regularly facetted compound eyes belonging to early Cambrian radiodontans suggests that high-resolution facetted eyes with superior optics may be the ground pattern organization for arthropods, predating the evolution of arthrodization and jointed post protocerebral appendages. Here we provide evidence that compound eye organization in stem-group euarthropods of the Cambrian can be understood in terms of eye morphologies diverging from this ancestral radiodontan-type ground pattern. We show that in certain Cambrian groups apposition eyes relate to fixed or mobile eyestalks, whereas other groups reveal concomitant evolution of sessile eyes equipped with optics typical of extant xiphosurans. Observations of fossil material, including that of trilobites and eurypterids, support the proposition that the ancestral compound eye was the apposition type. Cambrian arthropods include possible precursors of mandibulate eyes. The latter are the modified compound eyes, now sessile, and their underlying optic lobes exemplified by scutigeromorph chilopods, and the mobile stalked compound eyes and more elaborate optic lobes typifying Pancrustacea. Radical divergence from an ancestral apposition type is demonstrated by the evolution of chelicerate eyes, from doublet sessile-eyed stem-group taxa to special apposition eyes of xiphosurans, the compound eyes of eurypterids, and single-lens eyes of arachnids. Different eye types are discussed with respect to possible modes of life of the extinct species that possessed them, comparing these to extant counterparts and the types of visual centers the eyes might have served. PMID- 26276097 TI - Enhancer of zeste acts as a major developmental regulator of Ciona intestinalis embryogenesis. AB - The paradigm of developmental regulation by Polycomb group (PcG) proteins posits that they maintain silencing outside the spatial expression domains of their target genes, particularly of Hox genes, starting from mid embryogenesis. The Enhancer of zeste [E(z)] PcG protein is the catalytic subunit of the PRC2 complex, which silences its targets via deposition of the H3K27me3 mark. Here, we studied the ascidian Ciona intestinalis counterpart of E(z). Ci-E(z) is detected by immunohistochemistry as soon as the 2- and 4-cell stages as a cytoplasmic form and becomes exclusively nuclear thereafter, whereas the H3K27me3 mark is detected starting from the gastrula stage and later. Morpholino invalidation of Ci-E(z) leads to the total disappearance of both Ci-E(z) protein and its H3K27me3 mark. Ci-E(z) morphants display a severe phenotype. Strikingly, the earliest defects occur at the 4-cell stage with the dysregulation of cell positioning and mitotic impairment. At later stages, Ci-E(z)-deficient embryos are affected by terminal differentiation defects of neural, epidermal and muscle tissues, by the failure to form a notochord and by the absence of caudal nerve. These major phenotypic defects are specifically rescued by injection of a morpholino-resistant Ci-E(z) mRNA, which restores expression of Ci-E(z) protein and re-deposition of the H3K27me3 mark. As observed by qPCR analyses, Ci-E(z) invalidation leads to the early derepression of tissue-specific developmental genes, whereas late-acting developmental genes are generally down-regulated. Altogether, our results suggest that Ci-E(z) plays a major role during embryonic development in Ciona intestinalis by silencing early-acting developmental genes in a Hox-independent manner. PMID- 26276098 TI - E4-Ubiquitin ligase Ufd2 stabilizes Yap8 and modulates arsenic stress responses independent of the U-box motif. AB - Adaptation of Saccharomyces cerevisiae cells to arsenic stress is mediated through the activation of arsenic detoxification machinery by the Yap8 transcription factor. Yap8 is targeted by the ubiquitin proteasome system for degradation under physiological conditions, yet it escapes proteolysis in arsenic injured cells by a mechanism that remains to be elucidated. Here, we show that Ufd2, an E4-Ubiquitin (Ub) ligase, is upregulated by arsenic compounds both at mRNA and protein levels. Under these conditions, Ufd2 interacts with Yap8 mediating its stabilization, thereby controlling expression of ACR3 and capacity of cells to adapt to arsenic injury. We also show that Ufd2 U-box domain, which is associated to the ubiquitination activity of specific ubiquitin ligases, is dispensable for Yap8 stability and has no role in cell tolerance to arsenic stress. Thus, our data disclose a novel Ufd2 role beyond degradation. This finding is further supported by genetic analyses showing that proteins belonging to Ufd2 proteolytic pathways, namely Ubc4, Rad23 and Dsk2, mediate Yap8 degradation. PMID- 26276099 TI - The study of the Bithorax-complex genes in patterning CCAP neurons reveals a temporal control of neuronal differentiation by Abd-B. AB - During development, HOX genes play critical roles in the establishment of segmental differences. In the Drosophila central nervous system, these differences are manifested in the number and type of neurons generated by each neuroblast in each segment. HOX genes can act either in neuroblasts or in postmitotic cells, and either early or late in a lineage. Additionally, they can be continuously required during development or just at a specific stage. Moreover, these features are generally segment-specific. Lately, it has been shown that contrary to what happens in other tissues, where HOX genes define domains of expression, these genes are expressed in individual cells as part of the combinatorial codes involved in cell type specification. In this report we analyse the role of the Bithorax-complex genes - Ultrabithorax, abdominal-A and Abdominal-B - in sculpting the pattern of crustacean cardioactive peptide (CCAP) expressing neurons. These neurons are widespread in invertebrates, express CCAP, Bursicon and MIP neuropeptides and play major roles in controlling ecdysis. There are two types of CCAP neuron: interneurons and efferent neurons. Our results indicate that Ultrabithorax and Abdominal-A are not necessary for specification of the CCAP-interneurons, but are absolutely required to prevent the death by apoptosis of the CCAP-efferent neurons. Furthermore, Abdominal-B controls by repression the temporal onset of neuropeptide expression in a subset of CCAP efferent neurons, and a peak of ecdysone hormone at the end of larval life counteracts this repression. Thus, Bithorax complex genes control the developmental appearance of these neuropeptides both temporally and spatially. PMID- 26276100 TI - Flagellar membranes are rich in raft-forming phospholipids. AB - The observation that the membranes of flagella are enriched in sterols and sphingolipids has led to the hypothesis that flagella might be enriched in raft forming lipids. However, a detailed lipidomic analysis of flagellar membranes is not available. Novel protocols to detach and isolate intact flagella from Trypanosoma brucei procyclic forms in combination with reverse-phase liquid chromatography high-resolution tandem mass spectrometry allowed us to determine the phospholipid composition of flagellar membranes relative to whole cells. Our analyses revealed that phosphatidylethanolamine, phosphatidylserine, ceramide and the sphingolipids inositol phosphorylceramide and sphingomyelin are enriched in flagella relative to whole cells. In contrast, phosphatidylcholine and phosphatidylinositol are strongly depleted in flagella. Within individual glycerophospholipid classes, we observed a preference for ether-type over diacyl type molecular species in membranes of flagella. Our study provides direct evidence for a preferential presence of raft-forming phospholipids in flagellar membranes of T. brucei. PMID- 26276101 TI - Sex-specific dysregulation of cysteine oxidation and the methionine and folate cycles in female cystathionine gamma-lyase null mice: a serendipitous model of the methylfolate trap. AB - In addition to its role in the endogenous synthesis of cysteine, cystathionine gamma-lyase (CGL) is a major physiological source of the vasorelaxant hydrogen sulfide. Cgl null mice are potentially useful for studying the influence of this compound upon vascular tone and endothelial function. Here, we confirm a previous report that female Cgl null mice exhibit an approximate 45-fold increase in plasma total homocysteine compared to wild type controls. This level of homocysteine is approximately 3.5-fold higher than that observed in male Cgl null mice and is essentially equivalent to that observed in mouse models of cystathionine beta synthase deficient homocystinuria. Cgl null mice of both sexes exhibited decreased expression of methylenetetrahydrofolate reductase and cysteinesulfinate decarboxylase compared to WT controls. Female Cgl null mice exhibited a sex-specific induction of betaine homocysteine S-methyltransferase and methionine adenosyltransferase 1, alpha and a 70% decrease in methionine synthase expression accompanied by significantly decreased plasma methionine. Decreased plasma cysteine levels in female Cgl null mice were associated with sex specific dysregulation of cysteine dioxygenase expression. Comparative histological assessment between cystathionine beta-synthase and Cgl null mice indicated that the therapeutic potential of cystathionine against liver injury merits possible further investigation. Collectively, our data demonstrates the importance of considering sex when investigating mouse models of inborn errors of metabolism and indicate that while female Cgl null mice are of questionable utility for studying the physiological role of hydrogen sulfide, they could serve as a useful model for studying the consequences of methionine synthase deficiency and the methylfolate trap. PMID- 26276102 TI - Adolescent pregnancy; a determinant of bone mineral density in peri-menopausal women? AB - OBJECTIVE: The present study aims to determine the effects of a history of adolescent pregnancy (AP) on the bone mineral density (BMD) of perimenopausal women. METHODS: Overall, 240 women aged between 40 and 55 years, with a complaint of oligomenorrhea or amenorrhea not exceeding 1 year in duration, were evaluated. Evaluation included a DEXA scan and a detailed demographic survey for bone health. Comparison was made between women with a history of AP and those without. RESULTS: In total, 87 women who had a history of AP were compared with 153 women who did not have a history of AP. The study groups did not differ significantly for most of the evaluated demographic factors. Women with a history of AP had higher gravidity and parity. Comparison of T-scores revealed lumbar BMD to be unaffected by AP (P=0.184), whereas femoral BMD was positively influenced by a history of AP (0.78+/-0.65 vs -1.06+/-0.67; P=0.042). In covariance regression models, after adjusting for parity and age of first menarche, AP still positively influenced femoral BMD. Without a history of AP, women were at increased risk for osteoporosis of femoral neck (odds ratio, 2.8, 95% CI 1.75-4.8). CONCLUSIONS: The effects of AP on BMD are not well elucidated. Women with a history of AP had better femoral BMD scores, indicating a possible protective influence of AP on bone health. BRIEF SUMMARY: Pregnancy during adolescence is associated with a better femoral bone mineral density than pregnancy at an older age. However, the effects did not extend to lumbar spine bone mineral density. PMID- 26276103 TI - Hormone therapy and risk of venous thromboembolism among postmenopausal women. AB - Despite a decrease in the use of postmenopausal hormone therapy (HT) over the last decade, many women are still prescribed this treatment, as it remains the most effective means of counteracting climacteric symptoms. Its use declined when it was shown that HT increases the risk of breast cancer, stroke and venous thromboembolism (VTE). Nevertheless, that benefit/risk ratio was established among women using oral estrogens alone or combined with a specific progestogen and it cannot necessarily be extrapolated to other HTs. Oral estrogens increase the risk of VTE especially during the first year of treatment and past users revert to a similar risk as women who have never used them. There is now growing evidence that VTE risk among HT users strongly depends on the route of administration. Indeed, transdermal estrogens, unlike oral estrogens, are not associated with an increased VTE risk and biological data support this difference between oral and transdermal estrogens. In addition, transdermal estrogens may not confer additional risk in women at high risk of VTE. Significant differences in thrombotic risk between HT preparations also relate to the concomitant progestogen. Studies have consistently shown that VTE risk is higher among users of combined estrogens plus progestogens than among users of estrogens alone. With respect to the different pharmacological classes of progestogens, two observational studies found that norpregnane derivatives are associated with an increased VTE risk, whereas micronized progesterone may be safe with respect to thrombotic risk. In conclusion, transdermal estrogens alone or combined with micronized progesterone may represent the safest alternative for women who require HT. PMID- 26276104 TI - Chemoprevention or mastectomy for women at high risk of developing breast cancer. AB - Breast cancer (BC) is the most commonly diagnosed invasive cancer among women; in developed countries, BC occurs in one out of eight women during her lifetime. Many factors, both genetic and non-genetic, determine a woman's risk of breast cancer and several mathematical models have been proposed that determine the risk. It is important to identify those at high risk, as there are now effective preventive strategies, such as chemoprevention therapy and risk-reduction surgery. Risk-reduction agents are recommended for women aged 35 years or more who are at high risk of breast cancer. Tamoxifen is presently deemed to be the agent of choice. However, raloxifene may be preferable, at least for some postmenopausal women, because of its lack of effect on the endometrium and the reduced incidence of venous thromboembolic events compared with tamoxifen. Prophylactic surgery has been widely investigated. Bilateral mastectomy decreases the risk of developing breast cancer by approximately 90% in women at moderate or high risk and in known BRCA1/2 mutation carriers. This review summarizes the recent advances in the identification of women at high risk of developing breast cancer and reports on the strategies used to prevent breast cancer; the risk benefit balance of such preventive choices is also briefly analyzed. PMID- 26276105 TI - In-stent neointimal characteristics and late neointimal response after drug eluting stent implantation: A preliminary observation. AB - BACKGROUND: Progressive neointimal proliferation may lead to late restenosis and/or neoatherosclerosis after drug-eluting stent (DES) implantation. Late neointimal response may be different among different tissue characteristics. The aim of this study was to assess impact of in-stent neointimal characteristics on late neointimal response following DES implantation. METHODS: Serial (median 270 days and median 551 days after stent implantation) optical coherence tomography (OCT) examinations were performed in 42 stented lesions from 26 patients. In stent neointimal tissue was categorized as either homogeneous or heterogeneous neointima based on the OCT appearance at 1st follow-up. Serial changes in neointimal area (NIA) were compared between lesions with homogeneous neointima and those with heterogeneous neointima. RESULTS: At first follow-up, homogeneous neointima was observed in 22 (52%) and heterogeneous neointima in 20 (48%) lesions, respectively. During follow-up, NIA in lesions with homogeneous neointima decreased significantly (1.8+/-0.93 mm(2) to 1.5+/-0.88 mm(2), p<0.001). On the other hand, NIA in lesions with heterogeneous neointima did not change significantly (2.7+/-1.8 mm(2) to 2.8+/-1.6 mm(2), p=0.658). Homogeneous neointima was the only predictor of late neointimal regression (late neointimal regression defined as NIA at first follow-up - NIA at second follow-up <0) by multivariable analysis (odds ratio=7.591, 95% confidence interval: 1.616-35.67, p=0.010). CONCLUSIONS: OCT characteristics of neointima after DES implantation may be related to late neointimal progression or regression. PMID- 26276106 TI - Catalytic cyclometallation in steroid chemistry III: Synthesis of steroidal derivatives of 5Z,9Z-dienoic acid and investigation of its human topoisomerase I inhibitory activity. AB - Two approaches to stereoselective synthesis of steroid 5Z,9Z-dienoic acids were developed, the first one being based on the cross-cyclomagnesiation of 2-(hepta 5,6-dien-1-yloxy)tetrahydro-2H-pyran and 1,2-diene cholesterol derivatives on treatment with EtMgBr catalyzed by Cp2TiCl2, while the other involving the synthesis of esters of hydroxy steroids with (5Z,9Z)-tetradeca-5,9-dienedioic acid, prepared in two steps using homo-cyclomagnesiation of 2-(hepta-5,6-dien-1 yloxy)tetrahydro-2H-pyran as the key step. High inhibitory activity of the synthesized acids against human topoisomerase I (hTop1) was found. PMID- 26276107 TI - Prescription of enoxaparin is associated with decreasing pulmonary embolism mortality rate in Germany. AB - We analysed time trends in the pulmonary embolism (PE) mortality rates in Germany from 2004 and assessed for an association between the use of anticoagulants and PE caused mortality. We extracted age-specific number of deaths due to PE (ICD-10 I26) from 2004 to 2011 as available from the WHO mortality databases. In addition we derived defined daily dosage (DDD) of prescribed anticoagulants and the low molecular heparin Enoxaparin for the years 2004-2011 from the statutory health insurance-drug-information system reports. Age-standardized PE mortality per 100,000 decreased from 5.9283 in year 2004 to 4.4876 in 2011 (-24.3 %). Amounts of prescribed anticoagulants increased in this period from 271,810.7 * 1000 DDD to 416,611.8 * 1000 DDD (+53.3 %), that of Enoxaparin increased from 27,071.1 * 1000 DDD in 2004 97,276.5 * 1000 DDD in 2011. The PE mortality is negatively correlated with anticoagulants (-0.9463, p = 0.0004) as well as with enoxaparin ( 0.9740, p < 0.0001) and of DDD of Enoxaparin per 1000 insured (-0.9682, p < 0.0001). In univariate linear regression model, anticoagulants, Enoxaparin and Enoxaparin per 1000 insured all reach significance (p = 0.0004, p = 4.31 * 10(-5) and p = 0.0001 respectively). Multiple regression models show that Enoxaparin has the most robust effect. Including the time trend in the model does not alter the results. Our study shows that increasing number of prescribed Enoxaparin in an outpatient setting might be one determinant of decreasing PE mortality rate in Germany since 2004. PMID- 26276108 TI - pH tolerance in freshwater bacterioplankton: trait variation of the community as measured by leucine incorporation. AB - pH is an important factor determining bacterial community composition in soil and water. We have directly determined the community tolerance (trait variation) to pH in communities from 22 lakes and streams ranging in pH from 4 to 9 using a growth-based method not relying on distinguishing between individual populations. The pH in the water samples was altered to up to 16 pH values, covering in situ pH +/- 2.5 U, and the tolerance was assessed by measuring bacterial growth (Leu incorporation) instantaneously after pH adjustment. The resulting unimodal response curves, reflecting community tolerance to pH, were well modeled with a double logistic equation (mean R(2) = 0.97). The optimal pH for growth (pHopt) among the bacterial communities was closely correlated with in situ pH, with a slope (0.89 +/- 0.099) close to unity. The pH interval, in which growth was >=90% of that at pHopt, was 1.1 to 3 pH units wide (mean 2.0 pH units). Tolerance response curves of communities originating from circum-neutral pH were symmetrical, whereas in high-pH (8.9) and especially in low-pH (<5.5) waters, asymmetric tolerance curves were found. In low-pH waters, decreasing pH was more detrimental for bacterial growth than increasing pH, with a tendency for the opposite for high-pH waters. A pH tolerance index, using the ratio of growth at only two pH values (pH 4 and 8), was closely related to pHopt (R(2) = 0.83), allowing for easy determination of pH tolerance during rapid changes in pH. PMID- 26276109 TI - Buccal swabbing as a noninvasive method to determine bacterial, archaeal, and eukaryotic microbial community structures in the rumen. AB - Analysis of rumen microbial community structure based on small-subunit rRNA marker genes in metagenomic DNA samples provides important insights into the dominant taxa present in the rumen and allows assessment of community differences between individuals or in response to treatments applied to ruminants. However, natural animal-to-animal variation in rumen microbial community composition can limit the power of a study considerably, especially when only subtle differences are expected between treatment groups. Thus, trials with large numbers of animals may be necessary to overcome this variation. Because ruminants pass large amounts of rumen material to their oral cavities when they chew their cud, oral samples may contain good representations of the rumen microbiota and be useful in lieu of rumen samples to study rumen microbial communities. We compared bacterial, archaeal, and eukaryotic community structures in DNAs extracted from buccal swabs to those in DNAs from samples collected directly from the rumen by use of a stomach tube for sheep on four different diets. After bioinformatic depletion of potential oral taxa from libraries of samples collected via buccal swabs, bacterial communities showed significant clustering by diet (R = 0.37; analysis of similarity [ANOSIM]) rather than by sampling method (R = 0.07). Archaeal, ciliate protozoal, and anaerobic fungal communities also showed significant clustering by diet rather than by sampling method, even without adjustment for potentially orally associated microorganisms. These findings indicate that buccal swabs may in future allow quick and noninvasive sampling for analysis of rumen microbial communities in large numbers of ruminants. PMID- 26276110 TI - The gastrointestinal tract as a potential infection reservoir of digital dermatitis-associated treponemes in beef cattle and sheep. AB - Digital dermatitis (DD) is an important cause of lameness in dairy cattle worldwide. It has now been reported in beef cattle and also sheep (contagious ovine digital dermatitis [CODD]). Three Treponema phylogroups are consistently isolated from lesions, Treponema medium-like, Treponema phagedenis-like, and Treponema pedis. The gastrointestinal (GI) tract and feces are suggested sites of treponemal infection in dairy cattle; however, isolation of DD-associated treponemes from these areas has previously failed. This study surveyed gingival tissues, rectal tissues, and feces of beef cattle and sheep for the molecular presence (PCR) and isolation of the three cultivable DD-treponeme phylogroups. Of the sheep gingival (n = 40) and rectal (n = 40) tissues, 1/40 gingival tissues was positive for DD-associated treponemes (T. pedis), as were 3/40 rectal tissues (one containing T. medium-like and two containing T. pedis). No DD-associated treponeme DNA was amplified from beef cattle rectal tissues (n = 40); however, 4/40 beef gingival tissues were positive for DD-associated treponemes (all containing T. phagedenis-like). A T. phagedenis-like DD-associated treponeme was isolated from the rectal tissue of a CODD symptomatic sheep. Beef cattle (n = 41) and sheep (n = 79) feces failed to amplify DD-associated Treponema DNA. Twenty two treponemes were isolated from sheep feces; however, upon phylogenetic analysis, these clustered with the considered nonpathogenic treponemes. This study detected DD-associated treponemes in the GI tract tissues of sheep and beef cattle and successfully isolated a DD-associated treponeme from ruminant rectal tissue. This gives evidence that the GI tract is an important infection reservoir of DD-associated treponemes in multiple DD-infected species. PMID- 26276111 TI - Climate change and physical disturbance manipulations result in distinct biological soil crust communities. AB - Biological soil crusts (biocrusts) colonize plant interspaces in many drylands and are critical to soil nutrient cycling. Multiple climate change and land use factors have been shown to detrimentally impact biocrusts on a macroscopic (i.e., visual) scale. However, the impact of these perturbations on the bacterial components of the biocrusts remains poorly understood. We employed multiple long term field experiments to assess the impacts of chronic physical (foot trampling) and climatic changes (2 degrees C soil warming, altered summer precipitation [wetting], and combined warming and wetting) on biocrust bacterial biomass, composition, and metabolic profile. The biocrust bacterial communities adopted distinct states based on the mechanism of disturbance. Chronic trampling decreased biomass and caused small community compositional changes. Soil warming had little effect on biocrust biomass or composition, while wetting resulted in an increase in the cyanobacterial biomass and altered bacterial composition. Warming combined with wetting dramatically altered bacterial composition and decreased Cyanobacteria abundance. Shotgun metagenomic sequencing identified four functional gene categories that differed in relative abundance among the manipulations, suggesting that climate and land use changes affected soil bacterial functional potential. This study illustrates that different types of biocrust disturbance damage biocrusts in macroscopically similar ways, but they differentially impact the resident soil bacterial communities, and the communities' functional profiles can differ depending on the disturbance type. Therefore, the nature of the perturbation and the microbial response are important considerations for management and restoration of drylands. PMID- 26276112 TI - Spatial patterns of carbonate biomineralization in biofilms. AB - Microbially catalyzed precipitation of carbonate minerals is an important process in diverse biological, geological, and engineered systems. However, the processes that regulate carbonate biomineralization and their impacts on biofilms are largely unexplored, mainly because of the inability of current methods to directly observe biomineralization within biofilms. Here, we present a method for in situ, real-time imaging of biomineralization in biofilms and use it to show that Pseudomonas aeruginosa biofilms produce morphologically distinct carbonate deposits that substantially modify biofilm structures. The patterns of carbonate biomineralization produced in situ were substantially different from those caused by accumulation of particles produced by abiotic precipitation. Contrary to the common expectation that mineral precipitation should occur at the biofilm surface, we found that biomineralization started at the base of the biofilm. The carbonate deposits grew over time, detaching biofilm-resident cells and deforming the biofilm morphology. These findings indicate that biomineralization is a general regulator of biofilm architecture and properties. PMID- 26276113 TI - A New Class of Tungsten-Containing Oxidoreductase in Caldicellulosiruptor, a Genus of Plant Biomass-Degrading Thermophilic Bacteria. AB - Caldicellulosiruptor bescii grows optimally at 78 degrees C and is able to decompose high concentrations of lignocellulosic plant biomass without the need for thermochemical pretreatment. C. bescii ferments both C5 and C6 sugars primarily to hydrogen gas, lactate, acetate, and CO2 and is of particular interest for metabolic engineering applications given the recent availability of a genetic system. Developing optimal strains for technological use requires a detailed understanding of primary metabolism, particularly when the goal is to divert all available reductant (electrons) toward highly reduced products such as biofuels. During an analysis of the C. bescii genome sequence for oxidoreductase type enzymes, evidence was uncovered to suggest that the primary redox metabolism of C. bescii has a completely uncharacterized aspect involving tungsten, a rarely used element in biology. An active tungsten utilization pathway in C. bescii was demonstrated by the heterologous production of a tungsten-requiring, aldehyde oxidizing enzyme (AOR) from the hyperthermophilic archaeon Pyrococcus furiosus. Furthermore, C. bescii also contains a tungsten-based AOR-type enzyme, here termed XOR, which is phylogenetically unique, representing a completely new member of the AOR tungstoenzyme family. Moreover, in C. bescii, XOR represents ca. 2% of the cytoplasmic protein. XOR is proposed to play a key, but as yet undetermined, role in the primary redox metabolism of this cellulolytic microorganism. PMID- 26276114 TI - Fluorescence assay for evaluating microbicidal activity of hand antiseptics. AB - We developed a fluorescent beta-d-glucuronidase activity (BGA)-based assay for detecting and quantifying Escherichia coli in samples to assess the biocide efficacy of hand antiseptics. The fluorescence level is proportional to the number of viable E. coli organisms present. We compared our assay results to those of the E. coli plate count method specified by the European standard for testing hygienic hand rub disinfectant products (EN1500). The plate count method requires excessive handling and materials and is not valid if the number of organisms per plate is too low or high for counting in many of the samples. We optimized the fluorescent assay based on the cleavage of 4-methylumbelliferyl beta-d-glucuronide by adding 4-nitrophenyl-beta-d-glucuronide, a nonfluorogenic BGA substrate, to induce glucuronidase activity and reduce assay time. Furthermore, our method can be automated and eliminates the need for multiple dilutions. Fluorescence was temporally monitored, and the time required to reach a specific value of fluorescence was correlated with the initial number of viable E. coli organisms on the samples. There was a positive correlation (P < 0.05) with a high correlation coefficient (R(2) = 0.82) between the E. coli counts by plate count and fluorescence methods. Reported effects in fluorescent BGA were compared to the EN1500 plate count method with five hand disinfectants. We found our method more advantageous, because it was as sensitive as the EN1500 method, requires less time to complete, and is less expensive and less laborious than conventional plating techniques. PMID- 26276115 TI - Distribution, activities, and interactions of methanogens and sulfate-reducing prokaryotes in the Florida Everglades. AB - To gain insight into the mechanisms controlling methanogenic pathways in the Florida Everglades, the distribution and functional activities of methanogens and sulfate-reducing prokaryotes (SRPs) were investigated in soils (0 to 2 or 0 to 4 cm depth) across the well-documented nutrient gradient in the water conservation areas (WCAs) caused by runoff from the adjacent Everglades Agricultural Area. The methyl coenzyme M reductase gene (mcrA) sequences that were retrieved from WCA 2A, an area with relatively high concentrations of SO4 (2-) (>=39 MUM), indicated that methanogens inhabiting this area were broadly distributed within the orders Methanomicrobiales, Methanosarcinales, Methanocellales, Methanobacteriales, and Methanomassiliicoccales. In more than 3 years of monitoring, quantitative PCR (qPCR) using newly designed group-specific primers revealed that the hydrogenotrophic Methanomicrobiales were more numerous than the Methanosaetaceae obligatory acetotrophs in SO4 (2-)-rich areas of WCA-2A, while the Methanosaetaceae were dominant over the Methanomicrobiales in WCA-3A (with relatively low SO4 (2-) concentrations; <=4 MUM). qPCR of dsrB sequences also indicated that SRPs are present at greater numbers than methanogens in the WCAs. In an incubation study with WCA-2A soils, addition of MoO4 (2-) (a specific inhibitor of SRP activity) resulted in increased methane production rates, lower apparent fractionation factors [alphaapp; defined as (amount of delta(13)CO2 + 1,000)/(amount of delta(13)CH4 + 1,000)], and higher Methanosaetaceae mcrA transcript levels compared to those for the controls without MoO4 (2-). These results indicate that SRPs play crucial roles in controlling methanogenic pathways and in shaping the structures of methanogen assemblages as a function of position along the nutrient gradient. PMID- 26276116 TI - Hypothetical protein Avin_16040 as the S-layer protein of Azotobacter vinelandii and its involvement in plant root surface attachment. AB - A proteomic analysis of a soil-dwelling, plant growth-promoting Azotobacter vinelandii strain showed the presence of a protein encoded by the hypothetical Avin_16040 gene when the bacterial cells were attached to the Oryza sativa root surface. An Avin_16040 deletion mutant demonstrated reduced cellular adherence to the root surface, surface hydrophobicity, and biofilm formation compared to those of the wild type. By atomic force microscopy (AFM) analysis of the cell surface topography, the deletion mutant displayed a cell surface architectural pattern that was different from that of the wild type. Escherichia coli transformed with the wild-type Avin_16040 gene displayed on its cell surface organized motifs which looked like the S-layer monomers of A. vinelandii. The recombinant E. coli also demonstrated enhanced adhesion to the root surface. PMID- 26276117 TI - Identification of the mcpA and mcpM genes, encoding methyl-accepting proteins involved in amino acid and l-malate chemotaxis, and involvement of McpM-mediated chemotaxis in plant infection by Ralstonia pseudosolanacearum (formerly Ralstonia solanacearum phylotypes I and III). AB - Sequence analysis has revealed the presence of 22 putative methyl-accepting chemotaxis protein (mcp) genes in the Ralstonia pseudosolanacearum GMI1000 genome. PCR analysis and DNA sequencing showed that the highly motile R. pseudosolanacearum strain Ps29 possesses homologs of all 22 R. pseudosolanacearum GMI1000 mcp genes. We constructed a complete collection of single mcp gene deletion mutants of R. pseudosolanacearum Ps29 by unmarked gene deletion. Screening of the mutant collection revealed that R. pseudosolanacearum Ps29 mutants of RSp0507 and RSc0606 homologs were defective in chemotaxis to l-malate and amino acids, respectively. RSp0507 and RSc0606 homologs were designated mcpM and mcpA. While wild-type R. pseudosolanacearum strain Ps29 displayed attraction to 16 amino acids, the mcpA mutant showed no response to 12 of these amino acids and decreased responses to 4 amino acids. We constructed mcpA and mcpM deletion mutants of highly virulent R. pseudosolanacearum strain MAFF106611 to investigate the contribution of chemotaxis to l-malate and amino acids to tomato plant infection. Neither single mutant exhibited altered virulence for tomato plants when tested by root dip inoculation assays. In contrast, the mcpM mutant (but not the mcpA mutant) was significantly less infectious than the wild type when tested by a sand soak inoculation assay, which requires bacteria to locate and invade host roots from sand. Thus, McpM-mediated chemotaxis, possibly reflecting chemotaxis to l-malate, facilitates R. pseudosolanacearum motility to tomato roots in sand. PMID- 26276119 TI - Comparison of Griffiths-II and Bayley-II tests for the developmental assessment of high-risk infants. AB - INTRODUCTION: Two important risk factors for abnormal neurodevelopment are preterm birth and neonatal hypoxic ischemic encephalopathy. The new revisions of Griffiths Mental Development Scale (Griffiths-II, [1996]) and the Bayley Scales of Infant Development (BSID-II, [1993]) are two of the most frequently used developmental diagnostics tests. The Griffiths-II is divided into five subscales and a global development quotient (QD), and the BSID-II is divided into two scales, the Mental scale (MDI) and the Psychomotor scale (PDI). The main objective of this research was to establish the extent to which developmental diagnoses obtained using the new revisions of these two tests are comparable for a given child. MATERIAL AND METHODS: Retrospective study of 18-months-old high risk children examined with both tests in the follow-up Unit of the Clinic of Neonatology of our tertiary care university Hospital between 2011 and 2012. To determine the concurrent validity of the two tests paired t-tests and Pearson product-moment correlation coefficients were computed. Using the BSID-II as a gold standard, the performance of the Griffiths-II was analyzed with receiver operating curves. RESULTS: 61 patients (80.3% preterm, 14.7% neonatal asphyxia) were examined. For the BSID-II the MDI mean was 96.21 (range 67-133) and the PDI mean was 87.72 (range 49-114). For the Griffiths-II, the QD mean was 96.95 (range 60-124), the locomotors subscale mean was 92.57 (range 49-119). The score of the Griffiths locomotors subscale was significantly higher than the PDI (p<0.001). Between the Griffiths-II QD and the BSID-II MDI no significant difference was found, and the area under the curve was 0.93, showing good validity. All correlations were high and significant with a Pearson product-moment correlation coefficient >0.8. CONCLUSIONS: The meaning of the results for a given child was the same for the two tests. Two scores were interchangeable, the Griffiths-II QD and the BSID-II MDI. PMID- 26276120 TI - Rape Myths, Rape Scripts, and Common Rape Experiences of College Women: Differences in Perceptions of Women Who Have Been Raped. AB - Rape is prevalent at colleges. Although research suggests commonalities across many college women's rape experiences (e.g., perpetrators using multiple coercive strategies), vignettes used to assess rape perceptions often reflect false beliefs. Two studies varying a perpetrator's coercive tactics examine rape perceptions using vignettes reflecting rape myths, rape scripts, or many college women's common rape experiences. Participants perceive a woman who was raped more positively in vignettes reflecting common rape experiences versus those reflecting rape myths or scripts. Theoretical, educational, and research implications are discussed. PMID- 26276118 TI - Anaerobic growth of Corynebacterium glutamicum via mixed-acid fermentation. AB - Corynebacterium glutamicum, a model organism in microbial biotechnology, is known to metabolize glucose under oxygen-deprived conditions to l-lactate, succinate, and acetate without significant growth. This property is exploited for efficient production of lactate and succinate. Our detailed analysis revealed that marginal growth takes place under anaerobic conditions with glucose, fructose, sucrose, or ribose as a carbon and energy source but not with gluconate, pyruvate, lactate, propionate, or acetate. Supplementation of glucose minimal medium with tryptone strongly enhanced growth up to a final optical density at 600 nm (OD600) of 12, whereas tryptone alone did not allow growth. Amino acids with a high ATP demand for biosynthesis and amino acids of the glutamate family were particularly important for growth stimulation, indicating ATP limitation and a restricted carbon flux into the oxidative tricarboxylic acid cycle toward 2-oxoglutarate. Anaerobic cultivation in a bioreactor with constant nitrogen flushing disclosed that CO2 is required to achieve maximal growth and that the pH tolerance is reduced compared to that under aerobic conditions, reflecting a decreased capability for pH homeostasis. Continued growth under anaerobic conditions indicated the absence of an oxygen-requiring reaction that is essential for biomass formation. The results provide an improved understanding of the physiology of C. glutamicum under anaerobic conditions. PMID- 26276121 TI - Transverse colon volvulus in children: A case series and a review of the literature. AB - Volvulus of the transverse colon is very rare in children. Three cases that occurred in a short time span are described and the scarce literature is reviewed. All patients presented with colonic obstruction and in all three the condition was diagnosed at laparotomy, as CT-scanning is not an available option in either of the two institutions. The transverse colon had not become gangrenous but was resected after detorsion for redundancy. The postoperative course was complicated and relaparotomy had to be performed for reobstruction in all cases. Only if the 'reverse' bean sign is recognized on the preoperative plain abdominal radiograph this rare diagnosis can be suspected. PMID- 26276122 TI - Opposite Effects of Visual Cueing During Writing-Like Movements of Different Amplitudes in Parkinson's Disease. AB - BACKGROUND: Handwriting is often impaired in Parkinson's disease (PD). Several studies have shown that writing in PD benefits from the use of cues. However, this was typically studied with writing and drawing sizes that are usually not used in daily life. OBJECTIVE: This study examines the effect of visual cueing on a prewriting task at small amplitudes (<=1.0 cm) in PD patients and healthy controls to better understand the working action of cueing for writing. METHODS: A total of 15 PD patients and 15 healthy, age-matched controls performed a prewriting task at 0.6 cm and 1.0 cm in the presence and absence of visual cues (target lines). Writing amplitude, variability of amplitude, and speed were chosen as dependent variables, measured using a newly developed touch-sensitive tablet. RESULTS: Cueing led to immediate improvements in writing size, variability of writing size, and speed in both groups in the 1.0 cm condition. However, when writing at 0.6 cm with cues, a decrease in writing size was apparent in both groups (P < .001) and the difference in variability of amplitude between cued and uncued writing disappeared. In addition, the writing speed of controls decreased when the cue was present. CONCLUSIONS: Visual target lines of 1.0 cm improved the writing of sequential loops in contrast to lines spaced at 0.6 cm. These results illustrate that, unlike for gait, visual cueing for fine motor tasks requires a differentiated approach, taking into account the possible increases of accuracy constraints imposed by cueing. PMID- 26276124 TI - Pseudomonas alkylphenolica sp. nov., a bacterial species able to form special aerial structures when grown on p-cresol. AB - Pseudomonas sp. KL28T is an aerobic, rod-shaped bacterium that was isolated from the soil of Changwon, South Korea, based on its ability to grow in the presence of linear alkylphenols (C1-C5). Despite several studies on strain KL28T, it could not be assigned to any known species in the genus Pseudomonas. The name 'Pseudomonas alkylphenolia' was proposed for KL28T, but the strain had not until now been characterized taxonomically and the name currently has no standing in the bacterial nomenclature. A 16S rRNA gene sequence based phylogenetic analysis suggested an affiliation of strain KL28T with the Pseudomonas putida group, with Pseudomonas vranovensis DSM 16006T as the most closely related type strain (99.1 % similarity). A multilocus phylogenetic sequence analysis performed by concatenating 16S rRNA, gyrB, rpoD and rpoB partial gene sequences showed that isolate KL28T could be differentiated from P. vranovensis DSM 16006T (sequence similarity 93.7 %). Genomic comparisons of strain KL28T with the type strains of the species in the P. putida group using average nucleotide index based on blast (ANIb) and genome-to genome distances (GGDC) revealed 87.06 % and 32.20 % similarities with P. vranovensis DSM 16006T, respectively, as the closest type strain. Both values are far from the thresholds established for species differentiation. These results, together with differences in phenotypic features and chemotaxonomic analyses [fatty acids and whole-cell matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS], support the proposal of strain KL28T ( = JCM 16553T = KCTC 22206T) as the type strain of a novel species, for which the formerly proposed name, 'P. alkylphenolia', is correctly latinized as Pseudomonas alkylphenolica sp. nov. PMID- 26276123 TI - Preliminary Associations Between Brain-Derived Neurotrophic Factor, Memory Impairment, Functional Cognition, and Depressive Symptoms Following Severe TBI. AB - Background Traumatic brain injury (TBI) often leads to mood and cognitive complications, affecting functional recovery. Understanding neurobiological alterations common in post-TBI depression (PTD) and cognition may identify novel biomarkers for TBI complications. Brain-derived neurotrophic factor (BDNF) is a likely target based on evidence of reduced BDNF signaling in experimental TBI and depression models and its role in learning and memory. Objective To evaluate BDNF as a biomarker for PTD, cognitive impairment, and functional cognition in a prospective cohort with severe TBI. Methods Participants with TBI (n = 113) were evaluated for PTD (Patient Health Questionnaire-9 [PHQ-9]), cognitive impairment (cognitive composite score), and functional cognition (Functional Independence Measure-Cognition, FIM-Cog). BDNF levels were measured in cerebrospinal fluid and serum at 0 to 6 days postinjury and in serum at 6 and 12 months postinjury. RESULTS: Serum BDNF was reduced after TBI versus controls at all time points. Acute serum BDNF positively correlated with memory composites (6 months: r = 0.43, P = .019, n = 30; 12 months: r = 0.53, P = .005, n = 26) and FIM-Memory scores (6 months: r = 0.35, P = .019, n = 45; 12 months: r = 0.38, P = .018, n = 38). Acute serum BDNF negatively correlated with 12-month PHQ-9 scores (r = 0.38; P = .044; n = 29). At 12 months, chronic serum BDNF tended to be lower in participants with PTD (P = .07) and correlated with PHQ-9 scores (r = -0.41; P = .019; n = 32). Conclusions Acute BDNF associations with memory recovery may implicate hippocampal damage/degeneration. Comparatively, BDNF associations with PTD status were not as strong as associations with PTD severity. Further investigation may delineate longitudinal BDNF patterns, and BDNF responsive treatments, reflecting mood and cognitive recovery following TBI. PMID- 26276126 TI - Probenecid Application Prevents Clinical Symptoms and Inflammation in Experimental Autoimmune Encephalomyelitis. AB - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Neurological impairments are caused by axonal damage due to demyelination and neuroinflammation within the central nervous system. T cells mediate the neuroinflammation. The activation of T cells is induced by the release of adenosine triphosphate and involves purinergic receptors as well as pannexin (Panx) proteins. As Panx1 is expressed on T cells, we here propose that application of probenecid, a known Panx inhibitor, will prevent the onset of clinical symptoms in a mouse model of MS, the experimental autoimmune encephalomyelitis (EAE) model. EAE-induced mice received daily injections of probenecid. Disease scores, T cell numbers, and microglia activation were compared between experimental groups. Probenecid treatment resulted in lower disease scores as compared to EAE animals. Probenecid-treated animals also displayed fewer inflammatory lesions. Microglia activation was not altered by treatment. In conclusion, probenecid prevented the onset of EAE. PMID- 26276125 TI - Uncovering co-expression gene network modules regulating fruit acidity in diverse apples. AB - BACKGROUND: Acidity is a major contributor to fruit quality. Several organic acids are present in apple fruit, but malic acid is predominant and determines fruit acidity. The trait is largely controlled by the Malic acid (Ma) locus, underpinning which Ma1 that putatively encodes a vacuolar aluminum-activated malate transporter1 (ALMT1)-like protein is a strong candidate gene. We hypothesize that fruit acidity is governed by a gene network in which Ma1 is key member. The goal of this study is to identify the gene network and the potential mechanisms through which the network operates. RESULTS: Guided by Ma1, we analyzed the transcriptomes of mature fruit of contrasting acidity from six apple accessions of genotype Ma_ (MaMa or Mama) and four of mama using RNA-seq and identified 1301 fruit acidity associated genes, among which 18 were most significant acidity genes (MSAGs). Network inferring using weighted gene co expression network analysis (WGCNA) revealed five co-expression gene network modules of significant (P < 0.001) correlation with malate. Of these, the Ma1 containing module (Turquoise) of 336 genes showed the highest correlation (0.79). We also identified 12 intramodular hub genes from each of the five modules and 18 enriched gene ontology (GO) terms and MapMan sub-bines, including two GO terms (GO:0015979 and GO:0009765) and two MapMap sub-bins (1.3.4 and 1.1.1.1) related to photosynthesis in module Turquoise. Using Lemon-Tree algorithms, we identified 12 regulator genes of probabilistic scores 35.5-81.0, including MDP0000525602 (a LLR receptor kinase), MDP0000319170 (an IQD2-like CaM binding protein) and MDP0000190273 (an EIN3-like transcription factor) of greater interest for being one of the 18 MSAGs or one of the 12 intramodular hub genes in Turquoise, and/or a regulator to the cluster containing Ma1. CONCLUSIONS: The most relevant finding of this study is the identification of the MSAGs, intramodular hub genes, enriched photosynthesis related processes, and regulator genes in a WGCNA module Turquoise that not only encompasses Ma1 but also shows the highest modular correlation with acidity. Overall, this study provides important insight into the Ma1-mediated gene network controlling acidity in mature apple fruit of diverse genetic background. PMID- 26276127 TI - Protective Effect of Isorhamnetin on Lipopolysaccharide-Induced Acute Lung Injury in Mice. AB - Isorhamnetin has been reported to have anti-inflammatory, anti-oxidative, and anti-proliferative effects. The aim of this study was to investigate the protective effect of isorhamnetin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice by inhibiting the expression of cyclooxygenase-2 (COX-2). The effects of isorhamnetin on LPS-induced lung pathological damage, wet/dry ratios and the total protein level in bronchoalveolar lavage fluid (BALF), inflammatory cytokine release, myeloperoxidase (MPO) and superoxide dismutase (SOD) activities, and malondialdehyde (MDA) level were examined. In addition, the COX-2 activation in lung tissues was detected by Western blot. Isorhamnetin pretreatment improved the mice survival rates. Moreover, isorhamnetin pretreatment significantly attenuated edema and the pathological changes in the lung and inhibited protein extravasation in BALF. Isorhamnetin also significantly decreased the levels of inflammatory cytokines in BALF. In addition, isorhamnetin markedly prevented LPS-induced oxidative stress. Furthermore, isorhamnetin pretreatment significantly suppressed LPS-induced activation of COX-2. Isorhamnetin has been demonstrated to protect mice from LPS-induced ALI by inhibiting the expression of COX-2. PMID- 26276128 TI - Anti-Inflammatory Effect of Apigenin on LPS-Induced Pro-Inflammatory Mediators and AP-1 Factors in Human Lung Epithelial Cells. AB - Apigenin is one of the plant flavonoids present in fruits and vegetables, acting as an important nutraceutical component. It is recognized as a potential antioxidant, antimicrobial, and anti-inflammatory molecule. In the present study, the mechanism of anti-inflammatory action of apigenin on lipopolysaccharide (LPS) induced pro-inflammatory cytokines and activator protein-1 (AP-1) factors in human lung A549 cells was investigated. The anti-inflammatory activity of apigenin on LPS-induced inflammation was determined by analyzing the expression of pro-inflammatory cytokines, nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and different AP-1 factors. Apigenin significantly inhibited the LPS induced expression of iNOS, COX-2, expression of pro-inflammatory cytokines (IL 1beta, IL-2, IL-6, IL-8, and TNF-alpha), and AP-1 proteins (c-Jun, c-Fos, and JunB) including nitric oxide production. Study confirms the anti-inflammatory effect of apigenin by inhibiting the expression of inflammatory mediators and AP 1 factors involved in the inflammation and its importance in the treatment of lung inflammatory diseases. PMID- 26276129 TI - Inhibition of Radiation-Induced Oxidative Damage in the Lung Tissue: May Acetylsalicylic Acid Have a Positive Role? AB - The lung is relatively sensitive to irradiation. It is shown that acetylsalicylic acid (ASA) might reduce oxidative injury and that it has a place in protection from cancer. The aim of this study is to evaluate the potential radioprotective effects of ASA. Whole-body irradiation (6 Gy, single dose) was applied to the rats. Glutathione (GSH), malondialdehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) levels in the lung tissue were measured. Control (C), Radiation (R), Radiation + ASA (R + ASA; received irradiation and 25 mg/kg of ASA intraperitoneally (i.p.)), and Radiation + Amifostine (R + WR-2721; received irradiation and 200 mg/kg of WR-2721 i.p.) groups were used. The MPO levels decreased statistically significantly in the group administered ASA. Histopathologically, a radioprotective effect of ASA was more evident in the R + ASA group. ASA is an agent which has not been used as a radioprotector in the clinic yet, and it is worth supporting with more advanced studies. PMID- 26276130 TI - TLR4-MyD88-TRAF6-TAK1 Complex-Mediated NF-kappaB Activation Contribute to the Anti-Inflammatory Effect of V8 in LPS-Induced Human Cervical Cancer SiHa Cells. AB - The synthetic compound 7-4-[Bis-(2-hydroxyethyl)-amino]-butoxy-5-hydroxy-8 methoxy-2-phenylchromen-4-one (V8) is a novel flavonoid-derived compound. In this study, we investigated the effects of V8 on Toll-like receptor 4 (TLR4)-mediated inflammatory reaction in human cervical cancer SiHa cells and lipopolysaccharide (LPS)-induced TLR4 activity in cervical cancer SiHa (HPV16+) cells, but not in HeLa (HPV18+) and C33A (HPV-) cells. In addition, V8 inhibited LPS-induced expression of TLR4, MyD88, TRAF6 and phosphorylation of TAK1, and their interaction with TLR4 in SiHa cells, resulting in an inhibition of TLR4-MyD88 TRAF6-TAK1 complex. Moreover, V8 blocked LPS-induced phosphorylation of IkappaB and IKK, resulting in inhibition of the nuclear translocation of P65-NF-kappaB in SiHa cells. We also found that V8 reduced the expression of NF-kappaB target genes, such as those for COX-2, iNOS, IL-6, IL-8, CCL-2, and TNF-alpha in LPS stimulated SiHa cells. These results suggested that V8 exerted an anti inflammatory effect on SiHa cells by inhibiting the TLR4-MyD88-TRAF6-TAK1 complex mediated NF-kappaB activation. PMID- 26276132 TI - Navicular Stress Fractures. PMID- 26276131 TI - Spaceflight alters expression of microRNA during T-cell activation. AB - Altered immune function has been demonstrated in astronauts during spaceflights dating back to Apollo and Skylab; this could be a major barrier to long-term space exploration. We tested the hypothesis that spaceflight causes changes in microRNA (miRNA) expression. Human leukocytes were stimulated with mitogens on board the International Space Station using an onboard normal gravity control. Bioinformatics showed that miR-21 was significantly up-regulated 2-fold during early T-cell activation in normal gravity, and gene expression was suppressed under microgravity. This was confirmed using quantitative real-time PCR (n = 4). This is the first report that spaceflight regulates miRNA expression. Global microarray analysis showed significant (P < 0.05) suppression of 85 genes under microgravity conditions compared to normal gravity samples. EGR3, FASLG, BTG2, SPRY2, and TAGAP are biologically confirmed targets and are co-up-regulated with miR-21. These genes share common promoter regions with pre-mir-21; as the miR-21 matures and accumulates, it most likely will inhibit translation of its target genes and limit the immune response. These data suggest that gravity regulates T cell activation not only by transcription promotion but also by blocking translation via noncoding RNA mechanisms. Moreover, this study suggests that T cell activation itself may induce a sequence of gene expressions that is self limited by miR-21. PMID- 26276133 TI - ICD 10: A Primer for the Orthopedic Foot and Ankle Surgeon. AB - The use of the 10th Revision of the International Classification of Diseases (ICD 10) will likely be required as of October 2015. ICD-10 was developed to increase the specificity and accuracy of disease and injury reporting. The number of diagnostic codes in this system has increased substantially, and approximately half of all ICD-10 codes are related to the musculoskeletal system, whereas 25% of all codes are related to fractures. For most foot and ankle injuries, the new code structure includes location, laterality, degree of healing, and encounter type. At the provider level, navigating this system will initially be a complex task. Understanding the ICD-10 code structure, properly training appropriate staff, and financially preparing for implementation will minimize potential practice disruption. PMID- 26276134 TI - Long-term Follow-up of Dorsal Wedge Osteotomy for Pediatric Freiberg Disease. AB - BACKGROUND: Treatment for Freiberg disease has been largely conservative despite availability of various operative options for severe or refractory cases. The aim of this study was to evaluate the long-term results of pediatric patients with symptomatic Freiberg disease treated with intra-articular dorsal wedge osteotomy. METHODS: Pediatric patients treated for Freiberg disease with surgery between January 1982 and 1999 were identified and selected for long-term clinical evaluation. Patients were evaluated regarding operative satisfaction and clinical outcome, performed according to the American Orthopaedic Foot & Ankle Society (AOFAS) lesser toe metatarsophalangeal-interphalangeal scale and range of motion (ROM) of metatarsophalangeal (MTP) joint. Patients had radiographic assessment of degenerative joint status with anteroposterior and oblique foot x-ray. Twenty patients (18 female, 2 male; mean age 15.2 years; range 12-17 years) were identified. The mean follow-up period was 23.4 (range 15-32) years. RESULTS: The clinical outcomes of our patients were classified as excellent in 16 (80%) and good in 4 (20%). The AOFAS mean score was 96.8 (range 91-100) points at the last clinical appointment. A negative correlation between AOFAS score and time of follow-up (r's = -0.61, P < .001) was found. Also, a strong negative correlation was found between Smillie classification and AOFAS final score (r's = -0.88, P < .001). CONCLUSION: The patients were very satisfied with pain and quality of life at a mean follow-up time of 23.4 years. To our knowledge, this is the first long term follow-up report supporting the procedure described by Gauthier and Elbaz as a good option for operative treatment of Freiberg disease. LEVEL OF EVIDENCE: Level IV, retrospective case series. PMID- 26276135 TI - The Diet of Inmates: An Analysis of a 28-Day Cycle Menu Used in a Large County Jail in the State of Georgia. AB - Given the many well-documented relationships between diet and health, growing medical care expenses for those incarcerated, and limited information on foods served in correctional facilities, this study examined the nutritional adequacy of a 28-day cycle menu used in a large county jail in Georgia. When compared with Dietary Reference Intakes, provisions of energy (female inmates only), sodium, saturated fat, and cholesterol exceeded recommendations. Magnesium, potassium, and vitamins A, D, and E met less than two thirds of recommendations. Compared with MyPlate recommendations, grains were overrepresented, while vegetables, fruits, and dairy were underrepresented in the menu. Small menu changes could improve the menu's nutrient content and potentially increase inmates' health and well-being. PMID- 26276136 TI - Management of Skin and Soft Tissue Infections in a County Correctional Center: A Quality Improvement Project. AB - The number of antibiotic-resistant infections continues to increase. In 2005, there were nearly 11,406 deaths from methicillin-resistant Staphylococcus aureus (MRSA) infection in the United States. Since 1980, the United States has seen a 300% increase in the rate of incarceration. This is noteworthy because individuals who enter correctional facilities have an increased risk for MRSA skin and soft tissue infections (SSTIs) and the risk of colonization proportional to the length of stay. Correctional institutions have a vested interest in improving the screening and treatment of MRSA SSTIs, as it is a costly and potentially preventable problem. This article describes the process of implementing an MRSA screening and treatment policy in a county correctional center. PMID- 26276137 TI - The Effect of Blood Glucose Self-Monitoring Among Inmates With Diabetes. AB - The increasing prevalence and risk of complications from diabetes necessitate patient participation and attentiveness to select appropriate foods, perform regular physical activity, and be active in diabetes management and self maintenance. Diabetes is often largely asymptomatic; consequently, early diagnosis and treatment are necessary. Inmates are a unique population challenged by the increased prevalence of chronic conditions including diabetes. Diabetes standards for inmates contain diagnostic and treatment management guidelines that incorporate personal glucose monitoring for insulin users. In December 2009, the Federal Bureau of Prisons initiated a program to distribute glucose meters to insulin-dependent inmates to facilitate self-monitoring blood glucose. The purpose of this study was to evaluate the effect of these glucose meters on hemoglobin A1c levels. PMID- 26276138 TI - Boosting facility deliveries with results-based financing: a mixed-methods evaluation of the government midwifery incentive scheme in Cambodia. AB - BACKGROUND: Increasing the coverage of skilled attendance at births in a health facility (facility delivery) is crucial for saving the lives of mothers and achieving Millennium Development Goal five. Cambodia has significantly increased the coverage of facility deliveries and reduced the maternal mortality ratio in the last decade. The introduction of a nationwide government implemented and funded results-based financing initiative, known as the Government Midwifery Incentive Scheme (GMIS), is considered one of the most important contributors to this. We evaluated GMIS to explore its effects on facility deliveries and the health system. METHODS: We used a mixed-methods design. An interrupted time series model was applied, using routine longitudinal data on reported deliveries between 2006 and 2011 that were extracted from the health information system. In addition, we interviewed 56 key informants and performed 12 focus group discussions with 124 women who had given birth (once or more) since 2006. Findings from the quantitative data were carefully interpreted and triangulated with those from qualitative data. RESULTS: We found that facility deliveries have tripled from 19% of the estimated number of births in 2006 to 57% in 2011 and this increase was more substantial at health centres as compared to hospitals. Segmented linear regressions showed that the introduction of GMIS in October 2007 made the increase in facility deliveries and deliveries with skilled attendants significantly jump by 18 and 10% respectively. Results from qualitative data also suggest that the introduction of GMIS together with other interventions that aimed to improve access to essential maternal health services led to considerable improvements in public health facilities and a steep increase in facility deliveries. Home deliveries attended by traditional birth attendants decreased concomitantly. We also outline several operational issues and limitations of GMIS. CONCLUSIONS: The available evidence strongly suggests that GMIS is an effective mechanism to complement other interventions to improve health system performance and boost facility deliveries as well as skilled birth attendance; thereby contributing to the reduction of maternal mortality. Our findings provide useful lessons for Cambodia to further improve GMIS and for other low-income countries to implement similar results-based financing mechanisms. PMID- 26276139 TI - BP Targets in Older Adults with CKD: Additional Evidence, but Uncertainty Continues. PMID- 26276140 TI - Living Donor Kidney Transplantation: Best Practices in Live Kidney Donation- Recommendations from a Consensus Conference. PMID- 26276141 TI - Nephrologists as Educators: Clarifying Roles, Seizing Opportunities. AB - Nephrologists play an important role in providing medical education in a variety of settings, including the medical school classroom, nephrology consult service, outpatient clinic, and dialysis unit. Therefore, nephrologists interact with a variety of learners. In this article the current state of published literature in medical education in nephrology is reviewed. Eight attending roles are identified of the nephrologist as a medical educator in the academic settings: inpatient internal medicine service, nephrology inpatient consult service, inpatient ESRD service, outpatient nephrology clinic, kidney transplantation, dialysis unit, classroom teacher, and research mentor. Defining each of these distinct settings could help to promote positive faculty development and encourage more rigorous education scholarship in nephrology. PMID- 26276142 TI - Systolic BP and Mortality in Older Adults with CKD. AB - BACKGROUND AND OBJECTIVES: Optimal BP targets for older adults with CKD are unclear. This study sought to determine whether a nonlinear relationship between BP and mortality-as described for the broader CKD population and for older adults in the general population-is present for older adults with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A cohort of 21,015 adults age 65-105 years with a moderate or severe reduction in eGFR (<60 ml/min per 1.73 m(2)) were identified within the Kaiser Permanente Northwest Health Maintenance Organization population. The relationship between baseline systolic BP (SBP; <=120, 121-130, 131-140, 141-150, >150 mmHg; referent, 131-140 mmHg) and all-cause mortality across age groups (65-70, 71-80, and >80 years) was examined; patients were followed for up to 11 years after cohort entry. RESULTS: The median times at risk were 3.15 years, 3.53 years, and 2.76 years for adults age 65-70, 71-80, and >80 years, respectively. Mortality during follow-up was 19.6% for those age 65-70 years, 33.4% for those age 71-80 years, and 55.7% for those age >80 years. The relationship between SBP and mortality varied as a function of age. The risk of death was highest for patients with the lowest SBP in all age groups. Only among adults age 65-70 years was an SBP>140 mmHg associated with a higher risk of death compared with the referent category. Patterns of age modification of the relationship between SBP and mortality were consistent in all sensitivity analyses. CONCLUSIONS: In a cohort of older adults, the relationship between SBP and mortality varied systematically with age. A relationship between higher SBP and mortality was present only for younger members of this cohort and not for those older than 70. These results raise the question of whether the relative benefits and harms of lowering BP to recommended targets for older adults with CKD may vary as a function of age. PMID- 26276143 TI - Manuscript title: Facilitators and barriers to cotrimoxazole prophylaxis among HIV exposed babies: a qualitative study from Harare, Zimbabwe. AB - BACKGROUND: Implementation of cotrimoxazole prophylaxis (CTX-p) among HIV-exposed infants (HEI) is poor in southern Africa. We conducted a study to investigate barriers to delivery of CTX-p to HEI in Zimbabwe at each step of the care cascade. Here we report findings of the qualitative component designed to investigate issues related to adherence conducted among women identified as HIV positive whose babies were started on CTX-p postnatally. Of note, Zimbabwe also provided nevirapine prophylaxis for HIV exposed babies, so the majority were giving nevirapine and CTX-p to their babies. METHODS: Between Feb-Dec 2011, the first 20 HIV infected mothers identified were invited for in-depth interview 4 5months postnatally. Interviews were recorded, transcribed, translated and analysed thematically. RESULTS: All women desired their baby's health above all else, and were determined to do all they could to ensure their wellbeing. They did not report problems remembering to give drugs. The baby's apparent good health was a huge motivator for continued adherence. However, most women reported that their husbands were less engaged in HIV care, refusing to be HIV tested and in some cases stealing drugs prescribed for their wives for themselves. In two instances the man stopped the woman from giving CTX-p to the baby either because of fear of side effects or not appreciating its importance. Stigma continues to be an important issue. Mothers reported being reluctant to disclose their HIV status to other people so found it difficult to collect prescription refills from the HIV clinic for fear of being seen by friends/relatives. Some women reported that it was hard to administer the drugs if there were people around at home. Other challenges faced were stock-outs of CTX-p at the clinic, which occurred three times in 2011. The baby would then go without CTX-p if the woman could not afford buying at a private pharmacy. CONCLUSIONS: The study highlights that adherence knowledge and desire alone is insufficient to overcome the familial and structural barriers to maintaining CTX-p. Improving adherence to CTX-p among HEI will require interventions to improve male involvement, reduce HIV stigma in communities and ensure adequate supply of drugs. PMID- 26276144 TI - Effect of Structural Differences in Collagen Sponge Scaffolds on Tracheal Epithelium Regeneration. AB - OBJECTIVE: We developed an in situ regeneration-inducible artificial trachea composed of a porcine collagen sponge and polypropylene framework and used it for tracheal reconstruction. In the present study, collagen sponges with different structures were prepared from various concentrations of collagen solutions, and their effect on the regeneration of tracheal epithelium was examined. METHODS: Collagen sponges were prepared from type I and III collagen solutions. The structures of the sponges were analyzed using scanning electron microscopy (SEM). Artificial tracheae, which were formed using the collagen sponges with different structures, were implanted into rabbits, and regeneration of the tracheal epithelium on the artificial tracheae was evaluated by SEM analysis and histological examination. RESULTS: The SEM analysis showed that collagen sponges prepared from 0.5% and 1.0% collagen solutions had a porous structure. However, the sponges prepared from a 1.5% collagen solution had a nonporous structure. After implantation of artificial tracheae prepared from 0.5% and 1.0% collagen solutions, their luminal surfaces were mostly covered with epithelium within 14 days. However, epithelial reorganization occurred later on artificial tracheae prepared from the 1.5% collagen solution. CONCLUSION: Collagen sponges with a porous structure are suitable for regeneration of the tracheal epithelium in our artificial trachea. PMID- 26276145 TI - Does overexpression of HER-2 correlate with clinicopathological characteristics and prognosis in colorectal cancer? Evidence from a meta-analysis. AB - BACKGROUND: Previous studies have been inconsistent with respect to the reported associations between human epidermal growth factor receptor (HER-2/neu) overexpression in colorectal cancer. The aims of this meta-analysis are to assess its correlation with clinicopathological characteristics and prognostic significance in colorectal cancer. METHODS: Eligible studies were searched in Pubmed, Embase and Web of Science databases. The inclusion criteria were studies that assessed the relationship between HER-2 expression detected by immunohistochemistry (IHC) and the prognosis or clinicopathological features in patients with colorectal cancer (CRC). Subgroup analysis according to sex, tumor location, TNM stage, grade of differentiation and lymph node metastasis were produced. Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) were calculated to examine the risk or hazard association, and heterogeneity and publication bias analyses were also performed. RESULTS: A total of 18 studies comprising 2867 colorectal cancer patients were included to assess the association between HER-2 immunohistochemical expression and clinicopathological characteristics and survival. The overall analysis showed that there was no detectable relation between HER-2 expression and prognosis in colorectal cancer patients with the pooled HR of 1.08 (95% CI: 0.96-1.21, P = 0.21). With respect to clinicopathological features, there was also no detectable relation between HER-2 expression and sex (OR = 0.91, 95% CI: 0.72-1.15, P = 0.42), tumor location (OR = 1.21, 95% CI = 0.88-1.65, P = 0.24), grade of differentiation (OR = 1.03, 95% CI = 0.72-1.47, P = 0.86), TNM stages (OR = 0.72, 95% CI = 0.31-1.66, P = 0.44), or lymph node metastasis (OR = 1.90, 95% CI = 0.90-4.02, P = 0.09) in CRC. CONCLUSIONS: The finding from this present meta-analysis suggested that HER-2 overexpression was not related to clinicopathological characteristics and poor prognostic of colorectal cancer patients. PMID- 26276147 TI - Zoonotic helminths parasites in the digestive tract of feral dogs and cats in Guangxi, China. AB - BACKGROUND: In Guangxi, a province of southern China, an important number of dogs and cats roam freely in rural settings, and the presence of these animals in proximity of people may represent a risk of parasitic zoonoses. The objective of the present study was to investigate the presence and identify gastrointestinal helminths in feral carnivores in Guangxi province. Therefore, post mortem examination was performed in 40 dogs and in 39 cats. RESULTS: The Gastrointestinal helminths were found in all the necropsied dogs and in 37 out of 39 cats. Fifteen species were identified including 7 trematodes, 3 cestodes and 5 nematodes. Most of them may be responsible for zoonotic infections. CONCLUSIONS: Major zoonotic gastrointestinal helminths, including liver and intestinal flukes, Toxocara spp., and Ancylostoma spp., are present in feral dogs and cats in Guangxi, and may represent a significant risk for public health. PMID- 26276146 TI - Characterization of genome-wide H3K27ac profiles reveals a distinct PM2.5 associated histone modification signature. AB - BACKGROUND: Current studies of environmental health suggest a link between air pollution components, such as particulate matter (PM), and various diseases. However, the specific genes and regulatory mechanisms implicated in PM-induced diseases remain largely unknown. Epigenetic systems such as covalent modification of histones in chromatin may mediate environmental factors in gene regulation. Investigating the relationships between PM exposure and histone modification status may help understand the mechanisms underlying environment-associated health conditions. METHODS: In this study, we obtained genome-wide profiles of H3K27ac (histone 3 lysine 27 acetylation), known to be an active gene regulatory histone modification marker, in blood samples collected from four Chinese individuals exposed to high or low PM2.5 (particles with diameters up to 2.5 MUm). RESULTS: The genome-wide chromatin immunoprecipitation sequencing (ChIP Seq) data indicated a comprehensive differential H3K27ac landscape across the individual genomes, which was associated with high PM2.5. Moreover, a substantial number of these PM2.5-associated differential H3K27ac markers were in genes involved in immune cell activation, potentially linking these epigenetic changes with air pollution-induced immune and inflammatory responses. CONCLUSIONS: Our study provides the first genome-wide characterization of H3K27ac profiles in individuals subjected to different exposure levels of PM2.5. Future systematic investigations of the relationships between air pollutants and histone modifications in large population samples are warranted to elucidate the contributions of histone modifications to environment-associated diseases. PMID- 26276148 TI - Wheat waxy proteins: polymorphism, molecular characterization and effects on starch properties. AB - The starch fraction, comprising about 70% of the total dry matter in the wheat grain, can greatly affect the end-use quality of products made from wheat kernels, especially Asian noodles. Starch is associated with the shelf life and nutritional value (glycaemic index) of different wheat products. Starch quality is closely associated with the ratio of amylose to amylopectin, the two main macromolecules forming starch. In this review, we briefly summarise the discovery of waxy proteins-shown to be the sole enzymes responsible for amylose synthesis in wheat. The review particularly focuses on the different variants of these proteins, together with their molecular characterisation and evaluation of their effects on starch composition. There have been 19 different waxy protein variants described using protein electrophoresis; and at a molecular level 19, 15 and seven alleles described for Wx-A1, Wx-B1 and Wx-D1, respectively. This large variability, found in modern wheat and genetic resources such as wheat ancestors and wild relatives, is in some cases not properly ordered. The proper ordering of all the data generated is the key to enhancing use in breeding programmes of the current variability described, and thus generating wheat with novel starch properties to satisfy the demand of industry and consumers for novel high-quality processed food. PMID- 26276149 TI - Molecular characterization of waxy alleles in three subspecies of hexaploid wheat and identification of two novel Wx-B1 alleles. AB - KEY MESSAGE: Two novel Wx - B1 null alleles that enlarge the genetic variability for this wheat gene were characterized, whose effects on wheat quality could be different to those of the Wx - B1b allele. The starch composition of wheat grain has a primary influence on flour quality. Wheat starch consists of two types of glucose polymers: amylose (22-35% of the total) and amylopectin (68-75% of the total). Amylose is synthesized by waxy proteins. Several studies have contributed to the catalogue of waxy alleles available for breeders, and the search for novel alleles of these and other proteins related to flour quality continues. In this report, we describe the characterization of two novel Wx-B1 alleles (Wx-B1k and Wx-B1m) in a collection of macha, Indian dwarf and club wheat. Several accessions lacking Wx-B1 protein were detected, and some were caused by the common Wx-B1b null allele. Of the other accessions, four from Indian dwarf wheat showed the insertion of 4 bp within the seventh exon, and one from club wheat had a deletion of four nucleotides in the second exon. These mutations were novel and provisionally catalogued as Wx-B1k and Wx-B1m, respectively, and could be used to enlarge the genetic variability for this gene. PMID- 26276150 TI - Pharmacological modulation of ureteric peristalsis in a chronically instrumented conscious pig model: effect of adrenergic and nitrergic modulation. AB - PURPOSE: To evaluate the role of adrenergic and nitrergic signaling on ureteric peristaltic frequency and contraction force in vivo using a large animal model. METHODS: Twelve female pigs (72 +/- 4 kg) were chronically instrumented with an electronic pressure-monitoring catheter in the right ureter. Nephrostomy, cystostomy, and arterial and venous catheters were left in situ. Ureteral peristalsis was recorded before and after the administration of propranolol, isoprenaline, doxazosin, urapidil, phenylephrine, LNNA (Nomega-nitro-L-arginine), and L-arginine. RESULTS: alpha1-Adrenergic receptor stimulation resulted in an increased P max and peristaltic frequency. However, alpha1-inhibition decreased P max alone. Similarly, beta-adrenergic stimulation decreased P max and peristaltic frequency, whereas beta-inhibition increased only P max. LNNA administration increased P max in the distal ureter and hydrostatic pressure in the pyelocalyceal system. L-Arginine did not affect P max or frequency, but resulted in a significantly higher diuresis. Either agonist or antagonist of NO did not affect peristaltic frequency and length of contraction. CONCLUSIONS: Activation of alpha- and beta-adrenergic receptors, respectively, stimulates and inhibits ureteric peristalsis. The biological effect of NO on ureteric motility is regionally determined and corresponds to the distribution of NOS-positive nerves. Inhibition of NOS activity increases P max in the distal ureter and tonic activity of the ureteric muscle resulting in higher hydrostatic pressure in the renal pelvis. PMID- 26276151 TI - Early results and complications of prostatic arterial embolization for benign prostatic hyperplasia. AB - PURPOSE: To review current knowledge on clinical outcomes and peri-operative complications of prostatic arterial embolization (PAE) in patients treated for lower urinary tract symptoms (LUTS) related to benign prostatic obstruction (BPO). METHODS: A systematic review of the literature published from January 2008 to January 2015 was performed on PubMed/MEDLINE. RESULTS: Fifty-seven articles were identified, and four were selected for inclusion in this review. Only one randomized clinical trial compared transurethral resection of the prostate (TURP) to PAE. At 3 months after the procedure, mean IPSS reduction from baseline ranged from 7.2 to 15.6 points. Mean urine peak-flow improvement ranged from +3.21 ml/s to +9.5 ml/s. When compared to TURP, PAE was associated with a significantly lower IPSS reduction 1 and 3 months after the procedure. A trend toward similar symptoms improvement was however reported without statistical significance from 6 to 24 months. Major complications were rare with one bladder partial necrosis due to non-selective embolization. Mild adverse events occurred in 10 % of the patients and included transient hyperthermia, hematuria, rectal bleeding, painful urination or acute urinary retention. Further comparative studies are mandatory to assess post-operative rates of complications, especially acute urinary retention, after PAE and standard procedures. CONCLUSION: Early reports suggest that PAE may be a promising procedure for the treatment of patients with LUTS due to BPO. However, the low level of evidence and short follow-up of published reports preclude any firm conclusion on its mid-term efficiency. Further clinical trials are warranted before any use in clinical practice. PMID- 26276152 TI - Is there still a role for computed tomography and bone scintigraphy in prostate cancer staging? An analysis from the EUREKA-1 database. AB - PURPOSE: According to the current guidelines, computed tomography (CT) and bone scintigraphy (BS) are optional in intermediate-risk and recommended in high-risk prostate cancer (PCa). We wonder whether it is time for these examinations to be dismissed, evaluating their staging accuracy in a large cohort of radical prostatectomy (RP) patients. METHODS: To evaluate the ability of CT to predict lymph node involvement (LNI), we included 1091 patients treated with RP and pelvic lymph node dissection, previously staged with abdomino-pelvic CT. As for bone metastases, we included 1145 PCa patients deemed fit for surgery, previously staged with Tc-99m methylene diphosphonate planar BS. RESULTS: CT scan showed a sensitivity and specificity in predicting LNI of 8.8 and 98 %; subgroup analysis disclosed a significant association only for the high-risk subgroup of 334 patients (P 0.009) with a sensitivity of 11.8 % and positive predictive value (PPV) of 44.4 %. However, logistic multivariate regression analysis including preoperative risk factors excluded any additional predictive ability of CT even in the high-risk group (P 0.40). These data are confirmed by ROC curve analysis, showing a low AUC of 54 % for CT, compared with 69 % for Partin tables and 80 % for Briganti nomogram. BS showed some positivity in 74 cases, only four of whom progressed, while 49 patients with negative BS progressed during their follow-up, six of them immediately after surgery. CONCLUSIONS: According to our opinion, the role of CT and BS should be restricted to selected high-risk patients, while clinical predictive nomograms should be adopted for the surgical planning. PMID- 26276153 TI - Interpretative bias in spider phobia: Perception and information processing of ambiguous schematic stimuli. AB - This study investigates the interpretative bias in spider phobia with respect to rapid visuomotor processing. We compared perception, evaluation, and visuomotor processing of ambiguous schematic stimuli between spider-fearful and control participants. Stimuli were produced by gradually morphing schematic flowers into spiders. Participants rated these stimuli related to their perceptual appearance and to their feelings of valence, disgust, and arousal. Also, they responded to the same stimuli within a response priming paradigm that measures rapid motor activation. Spider-fearful individuals showed an interpretative bias (i.e., ambiguous stimuli were perceived as more similar to spiders) and rated spider like stimuli as more unpleasant, disgusting, and arousing. However, we observed no differences between spider-fearful and control participants in priming effects for ambiguous stimuli. For non-ambiguous stimuli, we observed a similar enhancement for phobic pictures as has been reported previously for natural images. We discuss our findings with respect to the visual representation of morphed stimuli and to perceptual learning processes. PMID- 26276154 TI - The Synergistic Effect of Selumetinib/Docetaxel Combination Therapy Monitored by [(18)F]FDG/[(18)F]FLT PET and Diffusion-Weighted Magnetic Resonance Imaging in a Colorectal Tumor Xenograft Model. AB - PURPOSE: Positron emission tomography (PET) and diffusion-weighted MRI (DW-MRI) were used to characterize the treatment effects of the MEK1/2 inhibitor selumetinib (AZD6244), docetaxel, and their combination in HCT116 tumor-bearing mice on the molecular level. PROCEDURES: Mice were treated with vehicle, selumetinib (25 mg/kg), docetaxel (15 mg/kg), or a combination of both drugs for 7 days and imaged at four time points with 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) or 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) followed by DW MRI to calculate the apparent diffusion coefficient (ADC). Data was cross validated using the Pearson correlation coefficient (PCC) and compared to histology (IHC). RESULTS: Each drug led to tumor growth inhibition but their combination resulted in regression. Separate analysis of PET or ADC could not provide significant differences between groups. Only PCC combined with IHC analysis revealed the highest therapeutic impact for combination therapy. CONCLUSION: Combination treatment of selumetinib/docetaxel was superior to the respective mono-therapies shown by PCC of PET and ADC in conjunction with histology. PMID- 26276156 TI - Changing non-participation in epidemiological studies of older people: evidence from the Cognitive Function and Ageing Study I and II. AB - BACKGROUND: non-participation in epidemiological studies threatens the generalisability of findings. OBJECTIVE: to investigate the change in non participation between the Medical Research Council Cognitive Function and Ageing Study (CFAS) I and II. DESIGN: a comparison of two epidemiological studies of older people using identical methods. SETTING: three geographical areas of the United Kingdom. SUBJECTS: older people aged 65 years and over. METHODS: the two studies were conducted approximately two decades apart between 1989 and 1994 (CFAS I) and between 2008 and 2011 (CFAS II). Random samples were drawn from primary care lists. We compared demographic factors associated with non participation. RESULTS: non-participation in CFAS II was higher than in CFAS I (45.3 versus 18.3%). After adjustment for confounders, in both CFAS I and CFAS II, women were more likely to decline to take part (CFAS I: odds ratio (OR) 1.3 95% confidence interval (CI) 1.2 to 1.4; CFAS II: 1.1 95% CI 1.1 to 1.2). Deprivation was associated with non-participation in both studies (highest versus lowest Townsend deprivation quintile, CFAS I: OR 1.4 95% CI 1.2 to 1.6; CFAS II: 2.0 95% CI 1.8 to 2.2). Age was not associated with non-participation in either study (CFAS I, P = 0.21; CFAS II, P = 0.47). CONCLUSIONS: non-participation in epidemiological studies of older people has increased substantially in the past two decades and public willingness to take part in studies of this kind would appear to be declining. As communities become more diverse and older people have increasing commitments on their time, new ways to engage prospective participants are urgently needed. PMID- 26276155 TI - Evaluation of CAIX and CAXII Expression in Breast Cancer at Varied O2 Levels: CAIX is the Superior Surrogate Imaging Biomarker of Tumor Hypoxia. AB - PURPOSE: Hypoxia is commonly observed in regions of primary tumors and metastases, and is associated with resistance to treatment, more aggressive tumor phenotypes and poor prognosis. Reliable and validated imaging biomarkers of hypoxia are needed for pre-clinical studies and clinical use. Expression of cell surface carbonic anhydrases IX and XII (CAIX and CAXII) in tumor cells has been associated with tumor hypoxia. CAIX and CAXII specific antibodies conjugated to fluorescent dye were evaluated for the non-invasive detection of hypoxia in vivo. PROCEDURES: Human breast cancer cell lines (MCF10A, DCIS, MCF7, ZR-75.1 and MDA mb231) were characterized for CAIX and CAXII expression by real-time RT-PCR and immunocytochemistry (ICC) under normoxic and hypoxic conditions. Immunohistochemical (IHC) staining of CAIX, CAXII and the commercially available exogenous hypoxia marker, pimonidazole, was performed using sections of ZR-75.1 and MDA-mb-231 orthotopic breast cancer xenograft tumors from nude mice. In vivo fluorescence imaging of ZR-75.1 tumors in animals housed at varied levels of oxygen was used to quantify the relative uptake of the CAIX and CAXII agents and a commercially available sulfonamide-based agent. Corresponding tumor sections were IHC stained for CAIX, CAXII and pimonidazole. RESULTS: CAIX mRNA expression was significantly higher (p < 0.05) in hypoxia for all cell lines, which was in agreement with protein expression by ICC. CAXII expression was mixed, with a modest hypoxia-related increase in two cell lines (p < 0.05) and no change in others. Quantified IHC staining of ZR-75.1 and MDA-mb-231 tumor sections showed that CAIX and CAXII expression was elevated in regions with pimonidazole staining, but CAXII levels were lower than CAIX. Tumor uptake of the CAIX targeted agent, and IHC staining of CAIX and pimonidazole in corresponding tumor sections were correlated, and co-registered, and shown to be significantly elevated by level of oxygenation (p < 0.001): hypoxia > normoxia > hyperoxia. However, the CAXII and sulfonamide agents were not significantly correlated with hypoxia. CONCLUSION: These studies suggest that the fluorescently labeled CAIX specific agent is a more robust indicator of hypoxia in vivo compared to the CAXII-specific agent or the agent specific to the CA active site. PMID- 26276158 TI - Selecting Question-Specific Genes to Reduce Incongruence in Phylogenomics: A Case Study of Jawed Vertebrate Backbone Phylogeny. AB - Incongruence between different phylogenomic analyses is the main challenge faced by phylogeneticists in the genomic era. To reduce incongruence, phylogenomic studies normally adopt some data filtering approaches, such as reducing missing data or using slowly evolving genes, to improve the signal quality of data. Here, we assembled a phylogenomic data set of 58 jawed vertebrate taxa and 4682 genes to investigate the backbone phylogeny of jawed vertebrates under both concatenation and coalescent-based frameworks. To evaluate the efficiency of extracting phylogenetic signals among different data filtering methods, we chose six highly intractable internodes within the backbone phylogeny of jawed vertebrates as our test questions. We found that our phylogenomic data set exhibits substantial conflicting signal among genes for these questions. Our analyses showed that non-specific data sets that are generated without bias toward specific questions are not sufficient to produce consistent results when there are several difficult nodes within a phylogeny. Moreover, phylogenetic accuracy based on non-specific data is considerably influenced by the size of data and the choice of tree inference methods. To address such incongruences, we selected genes that resolve a given internode but not the entire phylogeny. Notably, not only can this strategy yield correct relationships for the question, but it also reduces inconsistency associated with data sizes and inference methods. Our study highlights the importance of gene selection in phylogenomic analyses, suggesting that simply using a large amount of data cannot guarantee correct results. Constructing question-specific data sets may be more powerful for resolving problematic nodes. PMID- 26276157 TI - Experimental design for the optimization of propidium monoazide treatment to quantify viable and non-viable bacteria in piggery effluents. AB - BACKGROUND: Distinguishing between viable and dead bacteria in animal and urban effluents is a major challenge. Among existing methods, propidium monoazide (PMA) qPCR is a promising way to quantify viable cells. However, its efficiency depends on the composition of the effluent, particularly on total suspended solids (TSS)) and on methodological parameters. The aim of this study was evaluate the influence of three methodological factors (concentration of PMA, incubation time and photoactivation time) on the efficiency of PMA-qPCR to quantify viable and dead cells of Listeria monocytogenes used as a microorganism model, in two piggery effluents (manure and lagoon effluent containing 20 and 0.4 TSS g.kg(-1), respectively). An experimental design strategy (Doehlert design and desirability function) was used to identify the experimental conditions to achieve optimal PMA qPCR results. RESULTS: The quantification of viable cells of L. monocytogenes was mainly influenced by the concentration of PMA in the manure and by the duration of photoactivation in the lagoon effluent. Optimal values differed with the matrix: 55 MUM PMA, 5 min incubation and 56 min photoactivation for manure and 20 MUM PMA, 20 min incubation and 30 min photoactivation for lagoon effluent. Applied to five manure and four lagoon samples, these conditions resulted in satisfactory quantification of viable and dead cells. CONCLUSION: PMA-qPCR can be used on undiluted turbid effluent with high levels of TSS, provided preliminary tests are performed to identify the optimal conditions. PMID- 26276159 TI - Myroides indicus sp. nov., isolated from garden soil. AB - A novel aerobic, non-motile, rod-shaped, catalase- and oxidase-positive bacterial strain, designated UKS3T, was isolated from garden soil, and subjected to polyphasic taxonomic analysis. Strain UKS3T formed whitish, viscous colonies on nutrient agar and was Gram-staining negative. Phylogenetic analysis, based on 16S rRNA gene sequence, showed that maximum pairwise similarity occurs with representatives of the genus Myroides. The most closely related species include Myroides marinus JS-08T (92.7 % sequence similarity), Myroides phaeus MY15T (92.7 %), Myroides odoratus DSM 2801T (91.5 %) and Myroides odoratimimus CCUG 39352T (91.4 %). Strain UKS3T contained menaquinone-6 (MK-6) as the major respiratory quinone and iso-C15 : 0 (40.2 %), anteiso-C15 : 0 (9.4 %) and iso-C17 : 0 3-OH (8.5 %) as major fatty acids. Phosphatidylethanolamine, phospholipids and three aminolipids were the major polar lipids. The DNA G+C content of strain UKS3T was 36.8 +/- 2.0 mol%. On the basis of phenotypic, chemotaxonomic and molecular analysis, strain UKS3T represents a novel species of the genus Myroides, for which the name Myroides indicus sp. nov., is proposed. The type strain is UKS3T ( = DSM 28213T = NCIM 5555T ). PMID- 26276160 TI - MiR-32 contributed to cell proliferation of human breast cancer cells by suppressing of PHLPP2 expression. AB - MicroRNAs (miRNAs) have been identified as important regulators that potentially play critical roles in various biological and pathological processes of cancer cells. The aim of the present study was to investigate the expression of miR-32 in breast cancer and its biological role in tumor progression. MiR-32 expression was markedly upregulated in breast cancer tissues and breast cancer cells. Ectopic expression of miR-32 promoted cell proliferation of breast cancer, whereas miR-32-in suppressed this function. Mechanically, data from luciferase reporter assays revealed that miR-32 directly targeted to the 3'-untranslated region (3'-UTR) of PHLPP2. Overexpression of miR-32 led to downregulation of PHLPP2 protein, which resulted in the downregulation of p21 and upregulation of cyclin D1 and p-Rb. In functional assays, PHLPP2-silenced in miR-32-in transfected ZR-75-30 cells have positive effect to promote cell proliferation, suggesting that direct PHLPP2 downregulation is required for miR-32-induced cell proliferation of breast cancer. Our findings highlighted the importance of miR-32 in promoting tumor progression, and implicate miR-32 as a potential therapeutic target in breast cancer. PMID- 26276161 TI - Aruna Shanbaug: Is Her Demise the End of the Road for Legislation on Euthanasia in India? AB - Aruna Ramachandra Shanbaug breathed her last after 42 years of being in a persistent vegetative state. Euthanasia in any form is not permitted in India and it was only in the year 2011 that a petition was filed in the court that urged the cessation of her force feeding with a nasogastric tube and the request for her peaceful death. What followed was a string of arguments and counter arguments relating to Euthanasia. The sad demise of Aruna Shanbaug is not the end of an individual, but may be the end of the road for clear cut guidelines and legislation on Euthanasia in India. PMID- 26276162 TI - Some Ethical Concerns About Human Induced Pluripotent Stem Cells. AB - Human induced pluripotent stem cells can be obtained from somatic cells, and their derivation does not require destruction of embryos, thus avoiding ethical problems arising from the destruction of human embryos. This type of stem cell may provide an important tool for stem cell therapy, but it also results in some ethical concerns. It is likely that abnormal reprogramming occurs in the induction of human induced pluripotent stem cells, and that the stem cells generate tumors in the process of stem cell therapy. Human induced pluripotent stem cells should not be used to clone human beings, to produce human germ cells, nor to make human embryos. Informed consent should be obtained from patients in stem cell therapy. PMID- 26276163 TI - Scenes, Spaces, and Memory Traces: What Does the Hippocampus Do? AB - The hippocampus is one of the most closely scrutinized brain structures in neuroscience. While traditionally associated with memory and spatial cognition, in more recent years it has also been linked with other functions, including aspects of perception and imagining fictitious and future scenes. Efforts continue apace to understand how the hippocampus plays such an apparently wide ranging role. Here we consider recent developments in the field and in particular studies of patients with bilateral hippocampal damage. We outline some key findings, how they have subsequently been challenged, and consider how to reconcile the disparities that are at the heart of current lively debates in the hippocampal literature. PMID- 26276164 TI - Local infiltration analgesia versus continuous interscalene brachial plexus block for shoulder replacement pain: a randomized clinical trial. AB - BACKGROUND: Shoulder replacement involves significant post-operative pain, which is often managed by continuous interscalene brachial plexus block. Catheter displacement and complications limit the beneficial effect of the block. Local infiltration analgesia (LIA) has provided good results in knee replacement. We aimed to assess the effectiveness of LIA for pain after shoulder replacement. METHODS: Patients scheduled for primary shoulder replacement under general anaesthesia were randomized to receive either local infiltration analgesia (LIA) (150 ml ropivacaine 0.2 % with epinephrine intra-operatively) or interscalene brachial plexus catheter (ISC) (ropivacaine 0.75 %, 7 ml bolus followed by 48-h 5 ml/h infusion). The primary outcome was opioid consumption during the first 24 post-operative hours. Secondary outcomes were pain ratings, supplementary analgesics, and side effects for 3 days, and complications until 3 months after surgery. RESULTS: Data were analysed for 61 patients (LIA 30, ISC 31). Twenty four-hour opioid consumption was higher in the LIA group compared with the ISC group: median (IQR) 95 mg (70-150 mg) versus 40 mg (8-76 mg) (P = 0.0001). No significant difference in opioid consumption was found between groups during the following 3 days. The LIA group had higher pain scores at 0, 2, 4, and 8 h. Two patients in the ISC group had long-lasting complications. CONCLUSIONS: The LIA technique cannot be recommended for shoulder replacement unless substantially modified. Occurrence of inadequate analgesia and complications following interscalene brachial plexus block prompt further studies into pain management after shoulder replacement. PMID- 26276165 TI - How intra-familial decision-making affects women's access to, and use of maternal healthcare services in Ghana: a qualitative study. AB - BACKGROUND: There is some evidence to suggest that within the household, family and community settings, women in sub-Saharan Africa often have limited autonomy and control over their reproductive health decisions. However, there are few studies that examine how intra-familial decision-making power may affect women's ability to access and use maternal health services. The purpose of this paper is to examine how intra-familial decision-making affects women's ability to access and use maternal health services. METHODS: We conducted 12 focus group discussions and 81 individual interviews with a total of 185 expectant and lactating mothers in six communities in Ghana. In addition, 20 key informant interviews were completed with healthcare providers. Attride-Stirling's thematic network analysis framework was used to analyse the data. RESULTS: Findings suggest that decision-making regarding access to and use of skilled maternal healthcare services is strongly influenced by the values and opinions of husbands, mothers-in-law, traditional birth attendants and other family and community members, more than those of individual childbearing women. In 49.2%, 16.2%, and 12.4% of cases in which women said they were unable to access maternal health services during their last pregnancy, husbands, mothers-in-law, and husband plus mothers-in-law, respectively, made the decision. Women themselves were the final decision-makers in only 2.7% of the cases. The findings highlight how the goal of improving access to maternal healthcare services can be undermined by women's lack of decision-making autonomy through complex processes of gender inequality, economic marginalisation, communal decision-making and social power. CONCLUSION: Interventions to improve women's use of maternity services should move beyond individual women to target different stakeholders at multiple levels, including husbands and mothers-in-law. PMID- 26276168 TI - Reliability of Total Renal Volume Computation in Polycystic Kidney Disease From Magnetic Resonance Imaging. AB - RATIONALE AND OBJECTIVES: Total renal volume (TRV) is an important quantitative indicator of the progression of autosomal dominant polycystic kidney disease (ADPKD). The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease proposes a method for TRV computation based on manual tracing and geometric modeling. Alternative approaches for TRV computation are represented by the application of advanced image processing techniques. In this study, we aimed to compare TRV estimates derived from these two different approaches. MATERIALS AND METHODS: The nearly automated technique for the analysis of magnetic resonance (MR) images was tested on 30 ADPKD patients. TRV was computed from both axial (KVax) and coronal (KVcor) acquisitions and compared to measurements based on geometric modeling (KVap) by linear regression and Bland-Altman analysis. In addition, to assess reproducibility, intraobserver and interobserver variabilities were computed. RESULTS: Linear regression analysis between KVax and KVcor resulted in an excellent correlation (KVax = 1KVcor - 0.78; r(2) = 0.997). Bland-Altman analysis showed a negligible bias and narrow limits of agreement (bias: -11.7 mL; SD: 54.3 mL). Similar results were obtained by comparison of volumes obtained applying the nearly automated method and the one based on geometric modeling (y = 0.98x + 75.9; r(2) = 0.99; bias: -53.7 mL; SD: 108.1 mL). Importantly, geometric modeling does not provide reliable TRV estimates in huge kidney affected by regional deformation. Intraobserver and interobserver variability resulted in very small percentage error <2%. CONCLUSIONS: The results of this study provide the feasibility of using a nearly automated approach for accurate and fast evaluation of TRV also in markedly enlarged ADPKD kidneys including exophytic cysts. PMID- 26276167 TI - Conventional Medical Education and the History of Simulation in Radiology. AB - Simulation is a promising method for improving clinician performance, enhancing team training, increasing patient safety, and preventing errors. Training scenarios to enrich medical student and resident education, and apply toward competency assessment, recertification, and credentialing are important applications of simulation in radiology. This review will describe simulation training for procedural skills, interpretive and noninterpretive skills, team based training and crisis management, professionalism and communication skills, as well as hybrid and in situ applications of simulation training. A brief overview of current simulation equipment and software and the barriers and strategies for implementation are described. Finally, methods of measuring competency and assessment are described, so that the interested reader can successfully implement simulation training into their practice. PMID- 26276166 TI - Turnover of acetylcholine receptors at the endplate revisited: novel insights into nerve-dependent behavior. AB - The turnover of nicotinic acetylcholine receptors (AChR) is a critical factor that determines function and safety of neuromuscular transmission at the nerve muscle synapses, i.e. neuromuscular junctions (NMJs). Previously, three different populations of AChRs exhibiting distinct stereotypic and activity-dependent half life values were observed in mouse muscles. To address AChR turnover in more detail, we here employed a recently developed longitudinal radioiodine assay that is based on repetitive measurements of radio emission from the same animals over long periods of time in combination with systematic variation of the time elapsed between AChR pulse-labeling and muscle denervation. Modeling of the data revealed profiles of AChR de novo synthesis and receptor incorporation into the postsynaptic membrane. Furthermore, decay of pre-existing AChRs upon denervation showed a peculiar pattern corroborating earlier findings of a two-step stabilization of AChRs. PMID- 26276169 TI - Protective effect of soft contact lenses after Boston keratoprosthesis. AB - PURPOSE: To evaluate associations between preoperative diagnosis, soft contact lens (SCL) retention and complications. METHODS: A retrospective chart review was conducted of 92 adult patients (103 eyes) who received a Boston keratoprosthesis type I at the Massachusetts's Eye and Ear Infirmary or the Flaum Eye Institute. Records were reviewed for preoperative diagnosis, SCL retention and subsequent complications. Preoperative categories included 16 autoimmune (Stevens-Johnson syndrome, ocular cicatricial pemphigoid, rheumatoid arthritis and uveitis), 9 chemical injury and 67 'other' (aniridia, postoperative infection, dystrophies, keratopathies) patients. RESULTS: 50% of the lenses had been lost the first time after about a year. A subset (n=17) experienced more than 2 SCL losses per year; this group is comprised of 1 patient with autoimmune diseases, 2 patients with chemical injuries and 14 patients with 'other' diseases. The preoperative diagnosis was not predictive of contact lens retention. However, multivariate analysis demonstrated that the absence of a contact lens was an independent risk factor for postoperative complications, such as corneal melts with or without aqueous humour leak/extrusion and infections. CONCLUSIONS: Presence of a contact lens after Boston keratoprosthesis implantation decreases the risk of postoperative complications; this has been clinically experienced by ophthalmologists, but never before has the benefit of contact lens use in this patient population been statistically documented. PMID- 26276170 TI - Fronto-orbital mucocele and orbital involvement in occult obstructive frontal sinus disease. AB - AIMS: To describe the clinical features of orbital involvement arising from occult obstructive frontal sinus disease and to highlight key features to aid diagnosis. METHODS: A retrospective review of the case notes of 15 patients who presented to three regional oculoplastics units over a 7-year period were reviewed. Patient demographics, clinical characteristics, relevant medical history, microbiology results, imaging, management and outcomes were assessed. RESULTS: The mean age of our patients was 55 years. Pain was the presenting feature in 8 patients while 14 presented with upper lid swelling and redness. This swelling was medial in 60% and diffuse in 40% of patients. Proptosis was noted in 11 patients. The correct diagnosis was suspected in only 53% of patients at the time of first presentation to an ophthalmologist. The mean time from onset of symptoms to the time of correct diagnosis was 53 weeks (median 3 weeks). On direct questioning, eight patients reported a previous history of intermittent upper lid swelling and eight patients had a past history of sinusitis or frontal sinus trauma. CONCLUSIONS: We present a large series of patients with occult sinus disease presenting with orbital involvement. As patients with this potentially life-threatening condition are often misdiagnosed, we hope this paper draws the ophthalmologist's attention to key pearls in the history and examination to make a prompt diagnosis. PMID- 26276172 TI - Spectral Migration of Fluorescence in Graphene Oxide Aqueous Dispersions: Evidence for Excited-State Proton Transfer. AB - Aqueous dispersions of graphene oxide (GO) exhibit strong pH-dependent fluorescence in the visible that originates, in part, from the oxygenated functionalities present. Here we examine the spectral migration on nanosecond time-scales of the pH dependent features in the fluorescence spectra. We show, from time-resolved emission spectra (TRES) constructed from the wavelength dependent fluorescence decay curves, that the migration is associated with excited state proton transfer. Both 'intramolecular' and 'intermolecular' transfer involving the quasi-molecular oxygenated aromatic fragments are observed. As a prerequisite to the time-resolved measurements, we have correlated the changes in the steady state fluorescence spectra with the sequence of dissociation events that occur in GO dispersions at different values of pH. PMID- 26276171 TI - Neurotrophic factor-alpha1 modulates NGF-induced neurite outgrowth through interaction with Wnt-3a and Wnt-5a in PC12 cells and cortical neurons. AB - Wnt-3a and Wnt-5a signaling activities inhibit and promote neurite outgrowth, respectively, to regulate dendritic and axonal genesis during neurodevelopment. NF-alpha1, a neurotrophic factor, has been shown to modulate dendritic remodeling and negatively regulate the canonical Wnt-3a pathway. Here, we investigated whether NF-alpha1 could modify nerve growth factor (NGF)-induced neurite outgrowth through interaction with Wnt-3a and Wnt-5a in PC12 cells and mouse primary cortical neurons. We showed that NGF-induced neurite outgrowth was inhibited by Wnt-3a, and this inhibition was prevented by NF-alpha1. Western blot analysis revealed that NF-alpha1 reduced the expression of both beta-catenin in the canonical Wnt-3a pathway and Rho, a downstream effector of Wnt-3a's non canonical signaling pathway. Treatment of PC12 cells with a ROCK inhibitor prevented the inhibition of NGF-induced neurite outgrowth by Wnt-3a, suggesting that NF-alpha1 promotes neurite outgrowth in the presence of Wnt-3a by down regulating its canonical and non-canonical activities. Interestingly, treatment of PC12 cells with Wnt-5a, which formed a complex with NF-alpha1, induced neurite outgrowth that was enhanced by treatment with the combination of Wnt-5a, NGF, and NF-alpha1. These effects of NF-alpha1 on Wnt 3a's and Wnt 5a's regulation of neurite outgrowth in PC12 cells were also demonstrated in primary cultures of mouse cortical neurons. In addition, we showed in PC12 cells that NF-alpha1 acts by upregulating adenomatous polyposis coli (APC) accumulation at neurite tips, thereby providing positive and negative Wnt-3a/Wnt-5a mediated cues to modulate neurite outgrowth, a process important during neurodevelopment. PMID- 26276173 TI - Unfolding Pathway of a Globular Protein by Surfactants Monitored with Raman Optical Activity. AB - Protein denaturation by surfactants has received increased attention in the last years due to its implications in topics such as pharmaceutics, cosmetics, paints, or biotechnology. This phenomenon is highly dependent on the physicochemical (structural) properties of the denaturing agents. In this work, we have measured for the first time the Raman optical activity (ROA) of bovine serum albumin (BSA) in the presence of three surfactants (anionic, cationic, and neutral), which has allowed us to detect new spectroscopic insights of the protein-surfactant interaction that conventional Raman spectroscopy cannot. Our work proposes two new groups of ROA marker bands to explore the unfolding of BSA induced by surfactants, which are related to "polar" (amide I and III modes) and "apolar" (methylene bending and phenyl breathing modes) protein sections. The appearance of the former groups is related to the initial attack of the surfactant, while the second groups relate to the hydrophobic unfolding. PMID- 26276174 TI - Raman Enhancement via Polariton States Produced by Strong Coupling between a Localized Surface Plasmon and Dye Excitons at Metal Nanogaps. AB - Polarized Raman scattering measurement was carried out using a hybridized system of Ag nanodimer structures and organic dye molecules. Tuning of the localized surface plasmon resonance energy leads to modulation of the hybridized polariton energy. The anticrossing behavior of the polariton energy implies a strong coupling regime with maximum Rabi splitting energy of 0.39 eV. The observation proves the effective Raman enhancement via the excitation of the upper and the lower branches of the hybridized states at the gap of the metal dimer. Maximum Raman enhancement was obtained at an optimized resonant energy between the hybrid states and Raman excitation. PMID- 26276175 TI - Structural Dynamics in a "Breathing" Metal-Organic Framework Studied by Electron Paramagnetic Resonance of Nitroxide Spin Probes. AB - Reversible structural rearrangements ("breathing") of metal-organic frameworks (MOFs) are interesting and complex phenomena with many potential applications. They are often triggered by small amounts of adsorbed guest molecules; therefore, the guest-host interactions in breathing MOFs are intensively investigated. Due to the sensitivity limitations, most analytical methods require relatively high concentrations of guests in these studies. However, because guest molecules are not "innocent", breathing behavior may become suppressed and unperturbed structural states inaccessible. We propose here the use of guest nitroxide molecules in tiny concentrations (such as 1 molecule per 1000 unit cells), which serve as spin probes for electron paramagnetic resonance (EPR), for effective study of breathing phenomena in MOFs. Using a perspective MIL-53(Al) framework as an example, we demonstrate the great advantage of this general approach, which avoids perturbation of the framework structure and allows in-depth investigation of guest-host interactions in the breathing mode. PMID- 26276176 TI - Photoelectrochemical Behavior of Self-Assembled Ag/Co Plasmonic Nanostructures Capped with TiO2. AB - The use of localized surface plasmon resonance induced by Ag nanostructures is a promising way for high-efficiency photoelectric conversion. In plasmonic photoelectric conversion devices, however, the chemical instability of Ag in ambient atmosphere and its immediate deterioration have been a critical issue. Here, we propose a Ag-Co nanostructure array embedded in a TiO2 matrix as a plasmonic resonator that ensures long-term stability. We also developed an electrochemical process to remove surface Co nanoclusters protecting fresh Ag from exposure to air. This enabled us to "unseal" Ag at the desired time. Furthermore, we confirmed photoelectric conversion using Ag-Co-TiO2 nanocomposite films in contact with solution; the photoelectric conversion was substantially enhanced by the plasmon resonance of the Ag nanorods. The Ag nanostructures sealed in a TiO2 matrix are expected to be used in other application fields, such as catalytisis and sensing, in which a fresh Ag surface is needed. PMID- 26276177 TI - Time-Resolved EPR Study of Electron-Hole Dissociations Influenced by Alkyl Side Chains at the Photovoltaic Polyalkylthiophene:PCBM Interface. AB - Nanosecond time-resolved electron paramagnetic resonance (TREPR) spectroscopy has been utilized at T = 77 K to characterize alkyl side-chain effects on geometries and on the electronic couplings (VCR) of transient charge-separated (CS) states in the photoactive layers fabricated by the spin-coating of mixed solutions of regioregular polyalkylthiophenes (RR-P3AT) and [6,6]-C61-butyric acid methyl ester (PCBM). By increasing the alkyl side-chain number from 6 to 12 in P3AT, a highly distant and long-lived CS state has been obtained. This result is explained by a coupling of the hole dissociation to the polymer librations by the side-chains. From an exponential decay of VCR with respect to the CS distance, the attenuation factor (betae) has been determined to be betae = 0.2 A(-1). Such a long-range tunneling feature is explained by the generations of the shallowly trapped, delocalized electron-hole pairs by the dissociation of the hole toward pi-stacking directions at the organic photovoltaic interface. PMID- 26276178 TI - Revisiting the NIR-to-Visible Upconversion Mechanism in beta-NaYF4:Yb(3+),Er(3.). AB - Here, we show that the long-accepted mechanism for the production of red and blue emission through upconversion (UC) of 1 MUm excitation in Yb(3+)/Er(3+)-doped materials does not apply in the popular beta-NaYF4 host. We propose a new mechanism involving Yb(3+)-to-Er(3+) energy-transfer UC out of the green-emitting (2)H11/2,(4)S3/2 states that quantitatively accounts for all of the observed optical behavior. Rate constants for the relevant radiative and nonradiative processes are reported along with a prediction of the power dependence of the pulsed and continuous-wave UC quantum efficiency. PMID- 26276179 TI - Disentangling Electronic and Vibrational Coherence in the Phycocyanin-645 Light Harvesting Complex. AB - Energy transfer between chromophores in photosynthesis proceeds with near-unity quantum efficiency. Understanding the precise mechanisms of these processes is made difficult by the complexity of the electronic structure and interactions with different vibrational modes. Two-dimensional spectroscopy has helped resolve some of the ambiguities and identified quantum effects that may be important for highly efficient energy transfer. Many questions remain, however, including whether the coherences observed are electronic and/or vibrational in nature and what role they play. We utilize a two-color, four-wave mixing experiment with control of the wavelength and polarization to selectively excite specific coherence pathways. For the light-harvesting complex PC645, from cryptophyte algae, we reveal and identify specific contributions from both electronic and vibrational coherences and determine an excited-state structure based on two strongly coupled electronic states and two vibrational modes. Separation of the coherence pathways also uncovers the complex evolution of these coherences and the states involved. PMID- 26276180 TI - Formation of an Organic/Metal Interface State from a Shockley Resonance. AB - The emergence of an organic/metal interface state is studied for the interface between 3,4,9,10-perylene-tetracarboxylic acid dianhydride (PTCDA) and Ag(100) by means of time- and angle-resolved two-photon photoemission and density functional theory. The interface state is located in the projected band gap of Ag(100), 2.3 eV above the Fermi level, and has an electron lifetime in the 10 fs range. The interface state has no direct counterpart on the clean Ag(100) surface, which only exhibits a broad resonance at ~1 eV lower energy. Our results thus show that organic overlayers are able to shift such a resonance substantially and even qualitatively change its character to a distinct electronic state at the interface. PMID- 26276181 TI - Structural Characterization of the UV-Induced Fragmentation Products in an Ion Trap by Infrared Multiple Photon Dissociation Spectroscopy. AB - Protonated cinchona alkaloids and their dimers undergo photochemical reaction in the gas phase, leading to UV-specific photofragments, not observed by collision induced dissociation. Simultaneous coupling of UV and IR lasers with a Paul ion trap has been achieved for obtaining the vibrational spectrum of the fragments arising from the photodissociation. The structure of the photoproduced radical has been fully characterized by comparing the experimental spectrum to that simulated by DFT calculations. PMID- 26276182 TI - Velocity Fluctuations in Helical Propulsion: How Small Can a Propeller Be. AB - Helical propulsion is at the heart of locomotion strategies utilized by various natural and artificial swimmers. We used experimental observations and a numerical model to study the various fluctuation mechanisms that determine the performance of an externally driven helical propeller as the size of the helix is reduced. From causality analysis, an overwhelming effect of orientational noise at low length scales is observed, which strongly affects the average velocity and direction of motion of a propeller. For length scales smaller than a few micrometers in aqueous media, the operational frequency for the propulsion system would have to increase as the inverse cube of the size, which can be the limiting factor for a helical propeller to achieve locomotion in the desired direction. PMID- 26276183 TI - Real Time Dual-Channel Multiplex SERS Ultradetection. AB - Surface-enhanced Raman scattering (SERS) can be combined with microfluidics for rapid multiplex analyte screening. Through combination of the high intensity and complex signals provided by SERS with the flow characteristics of microfluidic channels, we engineered a microdevice that is capable of monitoring various analytes from different sources in real time. Detection limits down to the nM range may allow the generation of a new family of devices for remote, real time monitoring of environmental samples such as natural or waste waters and application to the high-throughput screening of multiple samples in healthcare diagnostics. PMID- 26276184 TI - Real Time Determination of the Electronic Structure of Unstable Reaction Intermediates during Au2O3 Reduction. AB - Chemical reactions are always associated with electronic structure changes of the involved chemical species. Determining the electronic configuration of an atom allows probing its chemical state and gives understanding of the reaction pathways. However, often the reactions are too complex and too fast to be measured at in situ conditions due to slow and/or insensitive experimental techniques. A short-lived Au2O compound has been detected for the first time under in situ conditions during the temperature-programmed reduction of Au2O3. A time-resolved resonant inelastic X-ray scattering experiment (RIXS) allowed the determination of changes in the Au electronic structure, enabling a better understanding of the reaction mechanism of Au(III) reduction. On the basis of time-resolved RIXS data analysis combined with genetic algorithm methodology, we determined the electronic structure of the metastable Au2O intermediate species. The data analysis showed a notably larger value for the lattice constant of the intermediate Au as compared to the theoretical predictions. With support of DFT calculations, we found that such a structure may indeed be formed and that the expanded lattice constant is due to the termination of Au2O on the Au2O3 structure. PMID- 26276185 TI - Tunable Optical Anisotropy of Seeded CdSe/CdS Nanorods. AB - We demonstrate structurally tunable optical anisotropy of seeded-growth CdSe/CdS dot-in-rod heterostructures using polarized excitation spectroscopy. The elongated anisotropic CdS shell confers optical anisotropy to the electronic transitions of the CdSe core. Although a rod-shaped shell geometry is a necessary precondition to observing polarized optical properties, the degree of linear polarization is not a strong function of aspect ratio. Rather, tuning the local anisotropy of the emissive core materials by changing the thickness of the anisotropic shell changes the degree of optical anisotropy more dramatically. As the diameter of the core material comprises a greater share (>90%) of the dot-in rod diameter, the anisotropy of the CdSe core states doubles compared to those for which the core represents <50% of the heterostructure diameter. PMID- 26276186 TI - Synthesized Blue Fluorescent Protein Analogue with Tunable Colors from Excited State Intramolecular Proton Transfer through an N-H...N Hydrogen Bond. AB - A synthesized blue fluorescent protein (BFP) chromophore analogue 2-BFP ((4Z)-4 [(1H-imidazol-2-yl)methylene]-1-methyl-2-phenyl-1H-imidazol-5(4H)-one) displays dual fluorescent emission that arises from the same Z-isomer. The larger Stokes shift emission is a result of excited-state intramolecular proton transfer (ESIPT) mediated by an N-H...N type of hydrogen bond. Compared to other green fluorescent protein (GFP) analogues with ESIPT such as o-HBDI, 2-BFP possesses greatly enhanced quantum yields and much slower proton-transfer rates. In addition, fluorescence up-conversion experiments revealed two rising components of lifetime for the tautomer formation of 2-BFP. The results imply that the relaxation of the N* state in 2-BFP triggers the proton transfer of the molecule. The weaker photoacidity of N-H is proposed to be crucial for these photophysical and photochemical properties. Finally, the ESIPT process in 2-BFP is inhibited in protic solvents (MeOH) or by the formation of metal-chelate complexes, providing insights for further developments and applications of ESIPT molecules. PMID- 26276187 TI - Evidence of Phonon-Assisted Auger Recombination and Multiple Exciton Generation in Semiconductor Quantum Dots Revealed by Temperature-Dependent Phonon Dynamics. AB - Auger processes, multiple exciton generation, and Auger recombination, provide and disturb a potential route to increase solar cell efficiencies by creating multiple charge carriers, respectively. Physical mechanisms of the Auger processes can be deduced from the temperature dependence. Our real-time ab initio simulation found logarithmic temperature dependence of the Auger rates in semiconductor quantum dots (QDs), which agrees well with the recent experimental observations. This anomalous temperature dependence is not only determined by static electronic structures of the QDs depending on temperature, but also attributed to dynamical electron-phonon couplings, directly demonstrating that the Auger processes are actually induced by the electron-phonon couplings and can be controlled by phonon modes. Our findings suggest that high-frequency and broad phonon modes of a QD including the surface ligands dictate efficient Auger dynamics in a QD. PMID- 26276188 TI - Tip-Enhanced Raman Spectroscopy with Picosecond Pulses. AB - Tip-enhanced Raman spectroscopy (TERS) can probe chemistry occurring at surfaces with both nanometer spectroscopic and submolecular spatial resolution. Combining ultrafast spectroscopy with TERS allows for picosecond and, in principle, femtosecond temporal resolution. Here we couple an optical parametric oscillator (OPO) with a scanning tunneling microscopy (STM)-TERS microscope to excite the tip plasmon with a picosecond excitation source. The plasmonic tip was not damaged with OPO excitation, and TER spectra were observed for two resonant adsorbates. The TERS signal under ultrafast pulsed excitation decays on the time scale of 10 s of seconds; whereas with continuous-wave excitation no decay occurs. An analysis of possible decay mechanisms and their temporal characteristics is given. PMID- 26276189 TI - Photocharging Artifacts in Measurements of Electron Transfer in Quantum-Dot Sensitized Mesoporous Titania Films. AB - Transient absorption and time-resolved photoluminescence measurements of high performance mesoporous TiO2 photoanodes sensitized with CuInSexS2-x quantum dots reveal the importance of hole scavenging in the characterization of photoinduced electron transfer. The apparent characteristic time of this process strongly depends on the local environment of the quantum dot/TiO2 junction due to accumulation of long-lived positive charges in the quantum dots. The presence of long-lived photoexcited holes introduces artifacts due to fast positive-trion Auger decay (60 ps time constant), which can dominate electron dynamics and thus mask true electron transfer. We show that the presence of a redox electrolyte is critical to the accurate characterization of charge transfer, since it enables fast extraction of holes and helps maintain charge neutrality of the quantum dots. Although electron transfer is observed to be relatively slow (19 ns time constant), a high electron extraction efficiency (>95%) can be achieved because in well-passivated CuInSexS2-x quantum dots neutral excitons have significantly longer lifetimes of hundreds of nanoseconds. PMID- 26276190 TI - Strategies on the Design of Nitrogen-Doped Graphene. AB - Substitutional nitrogen doping in graphene has been a very powerful tool to tailor the pristine property of graphene and furthermore extend its application. While nitrogen-doped graphene (N-graphene) has shown many potential applications in catalysis, electronics, sensors and so on, there is still a lack of accurate control of substitutional nitrogen doping, and higher performance toward various applications is always needed. This Perspective summarizes the ongoing developments toward better control of nitrogen doping. Moreover, two recent strategies aiming to promote the activity of N-graphene are also discussed. PMID- 26276191 TI - Redox-Tuned Three-Color Emission in Double (Mn and Cu) Doped Zinc Sulfide Quantum Dots. AB - The photoluminescence characteristics of colloidal Mn(2+) and Cu(2+) (double) doped zinc sulfide (ZnS) quantum dots (Qdots) could be drastically influenced by reactions with redox reagents. Importantly, experiments revealed Cu(+) in ZnS nanocrystals rather than Cu(2+), in conjunction with Mn(2+), as the emitting dopant. Thus, as-synthesized aqueous Qdots emitted orange (with peaks at 460 and 592 nm) due to the host and Mn(2+) dopant emissions. However, upon treatment with a reducing agent, the color changed to yellow with dual peaks positioned at 520 and 590 nm due to Cu(+) and Mn(2+) dopant emissions. The characteristics could be changed reversibly with appropriate redox reagents. Further, treatment with excess of an oxidizing agent led to blue emission with a single peak at 450 nm. PMID- 26276192 TI - Atomic Details of Interfacial Interaction in Gold Nanoparticles Supported on MgO(001). AB - Atomic-scale imaging using aberration-corrected scanning transmission electron microscopy reveals direct evidence for semicoherent interfacial epitaxy and coordinate-dependent surface contraction for the fcc (001) oriented Au nanoparticles (2-3 nm in diameter), suggesting that their interaction with the substrate is weaker than previously assumed. A significant change in interfacial separation distance from 2.47 +/- 0.12 A for the fcc (001) oriented Au nanoparticles to 3.07 +/- 0.11 A for the fcc (111) oriented Au nanoparticles has also been observed. These results are used to verify the atomistic models generated by the global optimization calculations, which shed further light on the intricate relation between the interfacial energy and the atomic structure of the nanoparticle and their combined effect on the inhomogeneous surface structural relaxation of supported nanoparticles. PMID- 26276193 TI - The Microscopic Physical Cause for the Density Maximum of Liquid Water. AB - The existence of a density maximum at 277 K is probably the most prominent anomaly among the many very special thermodynamic properties of liquid water. While usually attributed to so-called hydrogen bonding, the microscopic physical cause of this prominent anomaly is still elusive. Here we show that the density anomaly is caused by those short-range electrostatic forces, which are generated by the quadrupole and higher moments of the charge distributions present in liquid-phase water molecules. This conclusion derives from 20 ns replica exchange molecular-dynamics simulations with closely related polarizable four-, five-, and six-point water models. As soon as the model complexity suffices to represent the higher electrostatic moments with sufficient accuracy, the density temperature profile n(T) calculated for T ? [250,320] K at the standard pressure 1 bar locks in to the experimental observation. The corresponding six-point model is, therefore, the most simple available cartoon for liquid-phase water molecules. PMID- 26276194 TI - Throwing Salt into the Mix: Altering Interfacial Water Structure by Electrolyte Addition. AB - Interfacial water commonly distinguishes itself from the bulk phase by adopting a polar, ordered structure. It is well-established that electrolytes can act to perturb this structure; however, the nature of this perturbation remains a topic of interest. In this study, surface- and structure-sensitive nonlinear vibrational spectroscopy is used to monitor electrolyte-induced changes in interfacial water structure. Solution ionic strength was varied over 5 orders of magnitude, and spectra were collected from two mineral surfaces (fused silica and calcium fluoride) and two polymer surfaces (polystyrene and poly(methyl methacrylate)). Analysis of the spectra reveals striking similarities and differences between these four aqueous interfaces; trends in overall intensity do not always follow changes in the spectral shape. Our results reveal the complex interplay between surface charge, ion adsorption, and hydrophobicity in determining interfacial water structure in the presence of dissolved ions. PMID- 26276195 TI - Origin of the Surface-Induced First Hyperpolarizability in the C60/SiO2 System: SCC-DFTB Insight. AB - Using the self-consistent charge density functional tight binding (SCC-DFTB) method, C60 molecules physisorbed on an alpha-quartz slab are shown to display a first hyperpolarizability, whereas, owing to their symmetry, both the alpha quartz slab and C60 molecule have no first hyperpolarizabilities. A larger first hyperpolarizability is achieved when the lowest-lying (five- or six-membered) ring is situated in between two hydroxyl rows, rather than on top, because this situation favors orbital overlaps and charge transfer. Further analysis has demonstrated that (i) the first hyperpolarizability originates from the MO overlap and field-induced charge transfers from the neighboring substrate/adsorbate moieties but not to geometric relaxation of the C60 molecules at the interface and that (ii) larger first hyperpolarizabilities are associated with low surface coverage and with small distances between C60 and the surface. This contribution is a clear illustration of the emergence of second-order nonlinear optical responses (first hyperpolarizability) as a result of breaking the centrosymmetry. PMID- 26276196 TI - Design and Applications of Noncanonical DNA Base Pairs. AB - While the Watson-Crick base pairs are known to stabilize the DNA double helix and play a vital role in storage/replication of genetic information, their replacement with non-Watson-Crick base pairs has recently been shown to have interesting practical applications. Nowadays, theoretical calculations are routinely performed on very complex systems to gain a better understanding of how molecules interact with each other. We not only bring together some of the basic concepts of how mispaired or unnatural nucleobases interact with each other but also look at how such an understanding influences the prediction of novel properties and development of new materials. We highlight the recent developments in this field of research. In this Perspective, we discuss the success of DFT methods, particularly, dispersion-corrected DFT, for applications such as pH controlled molecular switching, electric-field-induced stacking of disk-like molecules with guanine quartets, and optical birefringence of alkali-metal coordinated guanine quartets. The synergy between theoretical models and real applications is highlighted. PMID- 26276197 TI - Origin of Photoluminescence and XAFS Study of (ZnS)1-x(AgInS2)x Nanocrystals. AB - Donor-Acceptor transition was previously suggested as a mechanism for luminescence in (ZnS)1-x(AgInS2)x nanocrystals. Here we show the participation of delocalized valence/conduction band in the luminescence. Two emission pathways are observed: Path-1 involves transition between a delocalized state and a localized state exhibiting higher energy and shorter lifetime (~25 ns) and Path-2 (donor-acceptor) involves two localized defect states exhibiting lower emission energy and longer lifetime (>185 ns). Surprisingly, Path-1 dominates (82% for x = 0.33) for nanocrystals with lower x, in sharp difference with prior assignment. Luminescence peak blue shifts systematically by 0.57 eV with decreasing x because of this large contribution from Path-1. X-ray absorption fine structure (XAFS) study of (ZnS)1-x(AgInS2)x nanocrystals shows larger AgS4 tetrahedra compared with InS4 tetrahedra with Ag-S and In-S bond lengths 2.52 and 2.45 A respectively, whereas Zn-S bond length is 2.33 A along with the absence of second nearest-neighbor Zn-S-metal correlation. PMID- 26276198 TI - Dynamic Crossovers and Stepwise Solidification of Confined Water: A (2)H NMR Study. AB - (2)H NMR reveals two dynamic crossovers of supercooled water in nanoscopic (~2 nm) confinement. At ~225 K, a dynamic crossover of liquid water is accompanied by formation of a fraction of solid water. Therefore, we do not attribute the effect to a liquid-liquid phase transition but rather to a change from bulk-like to interface-dominated dynamics. Moreover, we argue that the alpha process and beta process are observed in experiments above and below this temperature, respectively. Upon cooling through a dynamic crossover at ~175 K, the dynamics of the liquid fraction becomes anisotropic and localized, implying solidification of the corresponding water network, most probably, during a confinement-affected glass transition. PMID- 26276199 TI - Microslips to "Avalanches" in Confined, Molecular Layers of Ionic Liquids. AB - We have measured forces between mica surfaces across two hydrophobic ionic liquids with a surface forces apparatus. Both surface-adsorbed water and alkyl chain length on the imidazolium cation influence the structure of the nanoconfined film and the dynamics of film-thickness transitions. Friction shows accumulative microslips as precursors to collective "avalanches" that abruptly reduce friction momentarily. This behavior is interpreted as a consequence of interlayer ion correlations within the 1 to 2 nm thick film; we identify this to be analogous to the friction response of crackling noise systems over a broad range of sizes. PMID- 26276200 TI - A Guided Stochastic Energy-Domain Formulation of the Second Order Moller-Plesset Perturbation Theory. AB - We develop an alternative formulation in the energy-domain to calculate the second order Moller-Plesset (MP2) perturbation energies. The approach is based on repeatedly choosing four random energies using a nonseparable guiding function, filtering four random orbitals at these energies, and averaging the resulting Coulomb matrix elements to obtain a statistical estimate of the MP2 correlation energy. In contrast to our time-domain formulation, the present approach is useful for both quantum chemistry and real-space/plane wave basis sets. The scaling of the MP2 calculation is roughly linear with system size, providing a useful tool to study dispersion energies in large systems. This is demonstrated on a structure of 64 fullerenes within the SZ basis as well as on silicon nanocrystals using real-space grids. PMID- 26276201 TI - Photodissociation of Propionaldehyde at 248 nm: Roaming Pathway as an Increasingly Important Role in Large Aliphatic Aldehydes. AB - Time-resolved Fourier transform infrared emission spectroscopy is employed in the photolysis of propionaldehyde (CH3CH2CHO) at 248 nm to characterize the role of the roaming pathway. High-resolution spectra of CO are analyzed to yield a single Boltzmann rotational distribution for each vibrational level (nu = 1-4) with small rotational and large vibrational energy disposals. A roaming saddle point is found containing two far separated moieties of HCO and CH3CH2 with a weak interaction between them. Quasiclassical trajectory calculations on this configuration yield the CO energy flow behavior, consistent with the findings. The rate constant along the roaming pathway is evaluated to be larger by >1-2 orders of magnitude than those along tight transition state or three-body dissociation pathways. This work implies that the roaming mechanism plays an increasingly important role in aliphatic aldehydes as the molecular size becomes larger. PMID- 26276202 TI - Energy Diagram of Semiconductor/Electrolyte Junctions. PMID- 26276203 TI - Hot Hole Transfer Increasing Polaron Yields in Hybrid Conjugated Polymer/PbS Blends. AB - We use quasi-steady-state photoinduced absorption (PIA) to study charge generation in blends of poly(3-hexylthiophene-2,5-diyl) (P3HT) with PbS nanocrystal quantum dots as a function of excitation energy. We find that, per photon absorbed, the yield of photogenerated holes present on the conjugated polymer increases with pump energy, even at wavelengths where only the quantum dots absorb. We interpret this result as direct evidence for transfer of hot holes in these conjugated polymer/quantum dot blends. These results help understand the operation of hybrid organic/inorganic photovoltaics. PMID- 26276204 TI - Subpicosecond and Sub-Angstrom Time and Space Studies by Means of Light, X-ray, and Electron Interaction with Matter. AB - This Perspective article considers an experimental system that consists of ultrafast optical, electron, and X-ray time-resolved components. These techniques are used simultaneously on the same sample to study, in real time, the events that occur immediately upon disturbance with an ultrafast optical pulse. Excited states and metastable species are generated on the surface, and the electrical and mechanical waves propagating through the sample are recorded with subpicosecond and sub-Angstrom resolution. The characteristic of each technique is briefly described as a means of introducing the experimental system that intergrates these techniques. The processes evolved after femtosecond excitation of a Au single crystal have been monitored by these techniques. The data presented show changes with a resolution of 0.3 +/- 0.1 ps in optical thermoreflectance, 1.0 +/- 0.2 ps in electron Bragg diffraction, and 0.6 +/- 0.1 ps in X-ray diffraction intensity accompanying shift and broadening. PMID- 26276205 TI - The Increasing Impact of Multimedia and Social Media in Scientific Publications. PMID- 26276206 TI - Structure and Dynamics of Low-Density and High-Density Liquid Water at High Pressure. AB - Liquid water has a primary role in ruling life on Earth in a wide temperature and pressure range as well as a plethora of chemical, physical, geological, and environmental processes. Nevertheless, a full understanding of its dynamical and structural properties is still lacking. Water molecules are associated through hydrogen bonds, with the resulting extended network characterized by a local tetrahedral arrangement. Two different local structures of the liquid, called low density (LDW) and high-density (HDW) water, have been identified to potentially affect many different chemical, biological, and physical processes. By combining diamond anvil cell technology, ultrafast pump-probe infrared spectroscopy, and classical molecular dynamics simulations, we show that the liquid structure and orientational dynamics are intimately connected, identifying the P-T range of the LDW and HDW regimes. The latter are defined in terms of the speeding up of the orientational dynamics, caused by the increasing probability of breaking and reforming the hydrogen bonds. PMID- 26276207 TI - Polystyrene Nanoparticles Perturb Lipid Membranes. AB - Polystyrene is abundant in marine debris. Like most synthetic polymers, it degrades very slowly, producing smaller and smaller particles easily ingested by wildlife. The presence of plastic microscopic particles in fish and marine wildlife is massive and well documented, but its impact on cellular activity is not understood. Biological activity generally requires interaction with biological membranes, but this is difficult to study at the molecular scale in vivo. Here we use coarse-grained molecular simulations to determine the effect of nanosized polystyrene (PS) particles on the properties of model biological membranes. We find that PS nanoparticles permeate easily into lipid membranes. Dissolved in the membrane core, PS chains alter membrane structure, significantly reduce molecular diffusion, and soften the membrane. Moreover, PS severely affects membrane lateral organization by stabilizing raft-like domains. Changes in membrane properties and lateral organization can severely affect the activity of membrane proteins and thereby cellular function. PMID- 26276208 TI - Reflection Phase and Amplitude Determination of Short-Range Ordered Plasmonic Nanohole Arrays. AB - The reflection phase and amplitude of a short-range ordered gold plasmonic nanohole array are measured in the vis-NIR range using an interferometric substrate. The phase flip is observed around the minimum of the reflection amplitude, which is consistent with the resonance of a single oscillator. Above the resonance wavelength, the phase shift roughly follows that of a continuous metal film with the same thickness. Numerical simulation of the corresponding hexagonal long-range ordered nanohole array exhibits similar phase behavior with a sharper phase flip at the amplitude minimum, where the field enhancement is strongest. By changing the refractive index of the surrounding medium, larger phase shifts as well as positive and negative amplitude changes were observed around the resonance wavelength. This interferometric substrate method enables simultaneous broad-band phase and amplitude acquisition on the second time scale. PMID- 26276209 TI - High Contrast Visualization of Cell-Hydrogel Contact by Advanced Interferometric Optical Microscopy. AB - Hydrogels with tunable elasticity has been widely used as micromechanical environment models for cells. However, the imaging of physical contacts between cells and hydrogels with a nanometer resolution along the optical axis remain challenging because of low reflectivity at hydrogel-liquid interface. In this work, we have developed an advanced interferometric optical microscopy for the high contrast visualization of cell-hydrogel contact. Here, reflection interference contrast microscopy (RICM) was modified with a confocal unit, high throughput optics and coherent monochromatic light sources to enhance interferometric signals from cell-hydrogel contact zones. The advanced interferomety clearly visualized physical contacts between cells and hydrogels, and thus enabled the quantitative evaluation of the area of cell-hydrogel adhesion. PMID- 26276210 TI - Reactivity of the Strongest Oxidizing Species in Aqueous Solutions: The Short Lived Radical Cation H2O(*.). AB - The radical cation H2O(*+) formed under irradiation of liquid water undergoes an ultrafast proton transfer reaction and consequently exhibits an extremely short lifetime. The proton transfer yields an oxidizing OH(*) radical whose reactivity has been extensively studied. By contrast, H2O(*+) reactivity with molecules other than water has not been established experimentally and was subject to controversy. The direct oxidation by H2O(*+) can take place in various situations. In highly concentrated solutions, the radical cation H2O(*+) may also be involved in ultrafast electron transfer reactions. We have applied picosecond pulse radiolysis conducted at the electron accelerator ELYSE on solutions with various H2SO4 concentrations to determine the scavenging yield of H2O(*+). The yield of H2O(*+) at a few tens of femtoseconds is estimated to be around 5.3 * 10(-7) mol J(-1), and its reactivity is quantitatively determined. Moreover, a simple estimation of the reduction potential of this short-lived radical cation shows that it is the most powerful oxidizing species. PMID- 26276211 TI - Actions of KMUP-1, a xanthine and piperazine derivative, on voltage-gated Na(+) and Ca(2+) -activated K(+) currents in GH3 pituitary tumour cells. AB - BACKGROUND AND PURPOSE: 7-[2-[4-(2-Chlorophenyl)piperazinyl]ethyl]-1,3 dimethylxanthine (KMUP-1) is a xanthine-based derivative. It has soluble GC activation and K(+) -channel opening activity. Effects of this compound on ion currents in pituitary GH3 cells were investigated in this study. EXPERIMENTAL APPROACH: The aim of this study was to evaluate effects of KMUP-1 on the amplitude and gating of voltage-gated Na(+) current (INa ) in pituitary GH3 cells and in HEKT293T cells expressing SCN5A. Both the amplitude of Ca(2+) -activated K(+) current and the activity of large-conductance Ca(2+) -activated K(+) (BKCa ) channels were also studied. KEY RESULTS: KMUP-1 depressed the transient and late components of INa with different potencies. The IC50 values required for its inhibitory effect on transient and late INa were 22.5 and 1.8 MUM respectively. KMUP-1 (3 MUM) shifted the steady-state inactivation of INa to a hyperpolarized potential by -10 mV, despite inability to alter the recovery of INa from inactivation. In cell-attached configuration, KMUP-1 applied to bath increased BKCa -channel activity; however, in inside-out patches, this compound applied to the intracellular surface had no effect on it. It prolonged the latency in the generation of action currents elicited by triangular voltage ramps. Additionally, KMUP-1 decreased the peak INa with a concomitant increase of current inactivation in HEKT293T cells expressing SCN5A. CONCLUSIONS AND IMPLICATIONS: Apart from activating BKCa channels, KMUP-1 preferentially suppresses late INa . The effects of KUMP-1 on ion currents presented here constitute an underlying ionic mechanism of its actions. PMID- 26276212 TI - Lower Extremity Amputation and Mortality Rates in the Reconstructed Diabetic Charcot Foot and Ankle With External Fixation: Data Analysis of 116 Patients. AB - The aim of this study was to determine the lower extremity amputation and mortality rates of a group of patients who underwent reconstructive surgery using circular external fixation for treatment of diabetic Charcot neuroarthropathy (CN) of the foot and/or ankle. Existing studies regarding lower extremity amputation or mortality rates for diabetic CN of the foot and/or ankle have been performed on mostly conservatively treated patients. The objective of the statistical analysis in this studied population was to understand the difference in overall amputation and mortality rates between the 2 main groups: one with foot and/or ankle ulceration (group 1), and the other without ulceration or osteomyelitis (group 2, control group). Within group 1, 2 subgroups were established: one with osteomyelitis (group 1A) and the other without osteomyelitis (group 1B). Initially, a retrospective analysis of 150 consecutive surgically reconstructed diabetic foot and ankle cases using circular external fixation from January 2005 through December 2012 was conducted. Those which were not supported with the diagnosis of diabetic CN were excluded and the 2 other charts without proper follow-up duration (6 months) for analysis were removed, resulting in the final sample size of N = 116. There were a total of n = 7 (6.0%) below the knee amputations (group 1A = 1, group 1B = 4, and group 2 = 2) with a total of n = 5 mortalities (4.3%) (group 1A = 2, group 1B = 2, and group 2 = 1). The total amount of time for a lower extremity amputation event (n = 7) since the time of surgical reconstruction was 729.43 +/- 519.73 days (range 230-1777 days) while for a mortality event (n = 5), it was 1302.00 +/- 765.48 days (range 633 2499 days). LEVELS OF EVIDENCE: Prognostic, Level III: Retrospective study. PMID- 26276213 TI - Current approaches to cutaneous sarcomas: Dermatofibrosarcoma protuberans and cutaneous leiomyosarcoma. PMID- 26276214 TI - Cutaneous angiosarcoma. PMID- 26276215 TI - Fe65 negatively regulates Jagged1 signaling by decreasing Jagged1 protein stability through the E3 ligase Neuralized-like 1. AB - Fe65 is a highly conserved adaptor protein that interacts with several binding partners. Fe65 binds proteins to mediate various cellular processes. But the interacting partner and the regulatory mechanisms controlled by Fe65 are largely unknown. In this study, we found that Fe65 interacts with the C-terminus of Jagged1. Furthermore, Fe65 negatively regulates AP1-mediated Jagged1 intercellular domain transactivation in a Tip60-independent manner. We found that Fe65 triggers the degradation of Jagged1, but not the Jagged1 intracellular domain (JICD), through both proteasome and lysosome pathways. We also showed that Fe65 promotes recruitment of the E3 ligase Neuralized-like 1 (Neurl1) to membrane tethered Jagged1 and monoubiquitination of Jagged1. These three proteins form a stable trimeric complex, thereby decreasing Jagged1 targeting by ubiquitin mediated degradation. Consequently, Jagged1 is a novel binding partner of Fe65, and Fe65 may act as a novel effector of Jagged1 signaling. PMID- 26276216 TI - Sequence and expression variation in SUPPRESSOR of OVEREXPRESSION of CONSTANS 1 (SOC1): homeolog evolution in Indian Brassicas. AB - Whole genome sequence analyses allow unravelling such evolutionary consequences of meso-triplication event in Brassicaceae (~14-20 million years ago (MYA)) as differential gene fractionation and diversification in homeologous sub-genomes. This study presents a simple gene-centric approach involving microsynteny and natural genetic variation analysis for understanding SUPPRESSOR of OVEREXPRESSION of CONSTANS 1 (SOC1) homeolog evolution in Brassica. Analysis of microsynteny in Brassica rapa homeologous regions containing SOC1 revealed differential gene fractionation correlating to reported fractionation status of sub-genomes of origin, viz. least fractionated (LF), moderately fractionated 1 (MF1) and most fractionated (MF2), respectively. Screening 18 cultivars of 6 Brassica species led to the identification of 8 genomic and 27 transcript variants of SOC1, including splice-forms. Co-occurrence of both interrupted and intronless SOC1 genes was detected in few Brassica species. In silico analysis characterised Brassica SOC1 as MADS intervening, K-box, C-terminal (MIKC(C)) transcription factor, with highly conserved MADS and I domains relative to K-box and C-terminal domain. Phylogenetic analyses and multiple sequence alignments depicting shared pattern of silent/non-silent mutations assigned Brassica SOC1 homologs into groups based on shared diploid base genome. In addition, a sub-genome structure in uncharacterised Brassica genomes was inferred. Expression analysis of putative MF2 and LF (Brassica diploid base genome A (AA)) sub-genome-specific SOC1 homeologs of Brassica juncea revealed near identical expression pattern. However, MF2-specific homeolog exhibited significantly higher expression implying regulatory diversification. In conclusion, evidence for polyploidy-induced sequence and regulatory evolution in Brassica SOC1 is being presented wherein differential homeolog expression is implied in functional diversification. PMID- 26276217 TI - An Extended Minimal Physiologically Based Pharmacokinetic Model: Evaluation of Type II Diabetes Mellitus and Diabetic Nephropathy on Human IgG Pharmacokinetics in Rats. AB - Although many studies have evaluated the effects of type 2 diabetes mellitus (T2DM) on the pharmacokinetics (PK) of low molecular weight molecules, there is limited information regarding effects on monoclonal antibodies. Our previous studies have reported significant increases in total (2-4 fold) and renal (100 300 fold) clearance of human IgG, an antibody isotype, in Zucker diabetic fatty (ZDF) rats. Pioglitazone treatment incompletely reversed the disease-related PK changes. The objective of this study was to construct a mechanistic model for simultaneous fitting plasma and urine data, to yield physiologically relevant PK parameters. We propose an extended minimal physiologically based PK (mPBPK) model specifically for IgG by classifying organs as either leaky or tight vascular tissues, and adding a kidney compartment. The model incorporates convection as the primary mechanism of IgG movement from plasma into tissues, interstitial fluid (ISF) in extravascular distribution space, and glomerular filtration rate (GFR), sieving coefficient and fraction reabsorbed in the kidney. The model captured the plasma and urine PK profiles well, and simulated concentrations in ISF. The model estimated a 2-4 fold increase in nonrenal clearance from plasma and 30-120 fold increase in renal clearance with T2DM, consistent with the experimental findings, and these differences in renal clearance were related to changes in GFR, sieving coefficient, and proximal tubular reabsorption. In conclusion, the mPBPK model offers a more relevant approach for analyzing plasma and urine IgG concentration-time data than conventional models and provides insight regarding alterations in distributional and elimination parameters occurring with T2DM. PMID- 26276219 TI - Magnetic properties of magnetite synthesized by Magnetospirillum magnetotacticum MS-1 cultured with different concentrations of ferric iron. AB - OBJECTIVE: To clarify the effect of Fe(3+) concentration on magnetite formation, Magnetospirillum magnetotacticum MS-1 was cultured at various initial concentrations of Fe(3+) and the yield and magnetic properties of the cells were investigated. RESULTS: Although total cell yields (g/l) were not dependent on the initial concentration of Fe(3+) (0-68 uM) in the growth medium, the percentage of magnetic cells increased as the initial Fe(3+) concentration increased. The coercivity (H c) and saturation magnetization (M s) of dried MS-1 cells increased and the blocking temperature (T B) decreased as the initial Fe(3+) concentration increased. These values are similar to those reported previously. The Verwey transition temperature (T V) was almost identical for all initial Fe(3+) concentrations (95-97 K), except for medium without added Fe(3+) (0 uM; 88 K). CONCLUSION: Fe(3+) concentration strongly affects the magnetic properties of MS-1 cells, especially in the lower concentration range, suggesting that the Fe(3+) concentration should be considered when evaluating the magnetic properties of MS 1 cells. PMID- 26276218 TI - Drug Delivery Approaches in Addressing Clinical Pharmacology-Related Issues: Opportunities and Challenges. AB - Various drug delivery approaches can be used to maximize therapeutic efficacy and minimize side effects, by impacting absorption, distribution, metabolism, and elimination (ADME) of a drug compound. For those drugs with poor water solubility or low permeability, techniques such as amorphous solid dispersion, liposomes, and complexations have been used to improve their oral bioavailability. Modified release (MR) formulations have been widely used to improve patient compliance, as well as to reduce side effects, especially for those drugs with short half-lives or narrow therapeutic windows. More than ten drugs using sterile long-acting release (LAR) formulations with clear clinical benefit have been successfully marketed. Furthermore, drug delivery systems have been used in delaying drug clearance processes. Additionally, modifying the in vivo drug distribution using targeted delivery systems has significantly improved oncology treatments. All the drug delivery approaches have their advantages and limitations. For both brand and generic drugs, the achievement of consistent quality and therapeutic performance using drug delivery systems can also pose serious challenges in developing a drug for the market, which requires close collaboration among industry, academia, and regulatory agencies. With the advent of personalized medicines, there will be great opportunities and challenges in utilizing drug delivery systems to provide better products and services for patients. PMID- 26276220 TI - Watching a real moving object expands tactile duration: the role of task irrelevant action context for subjective time. AB - Although it is well established that action contexts can expand the perceived durations of action-related events, whether action contexts also impact the subjective duration of events unrelated to the action remains an open issue. Here we examined how the automatic implicit reactions induced by viewing task irrelevant, real moving objects influence tactile duration judgments. Participants were asked to make temporal bisection judgments of a tactile event while seeing a potentially catchable swinging ball. Approaching movement induced a tactile-duration overestimation relative to lateral movement and to a static baseline, and receding movement produced an expansion similar in duration to that from approaching movement. Interestingly, the effect of approaching movement on the subjective tactile duration was greatly reduced when participants held lightweight objects in their hands, relative to a hands-free condition, whereas no difference was obtained in the tactile-duration estimates between static hands free and static hands-occupied conditions. The results indicate that duration perception is determined by internal bodily states as well as by sensory evidence. PMID- 26276222 TI - Evaluating the Rare and Predicting the Worst: Lessons for Thyroid Nodules. PMID- 26276221 TI - Choroidal thickness measurements in migraine patients during attack-free period. AB - To identify any structural differences in macular choroidal thickness in migraine patients and compare them with that of control subjects by using spectral domain optic coherence tomography (SD-OCT). In this prospective study, choroidal thicknesses of 32 migraine patients during migraine attack-free period and 32 age and sex-matched healthy subjects were measured using SD-OCT. All patients underwent a complete ophthalmic examination before the measurements. The migraine patients were classified into the migraine with aura group or the migraine without aura group. Migraine severity was assessed by visual analog scale (VAS), migraine disability questionnaire (Migraine Disability Assessment Score (MIDAS), and Wong-Baker faces pain rating scale. Thirty eyes of 32 subjects (31 female and 1 male) in the migraine group and 32 eyes of 32 subjects (31 female and 1 male) in control group were evaluated. In the study group, 16 patients suffered migraine without aura (MWA) and 16 patients were diagnosed as migraine with aura (MA). The mean subfoveal choroidal thickness (SFCT) was 353.3 +/- 66.5 MUm in the control group versus 304.3 +/- 72.9 MUm and 276.1 +/- 61.4 MUm in MWA and MA groups, respectively. The difference in SFCT between the migraine patients and the controls was significant (p < 0.001). Additionally, a moderate correlation was found between SFCT and the VAS score and W baker score (r = 0.48, p = 0.008 and r = 0.43, p = 0.02, respectively). The choroidal thickness was found to decrease significantly not only in migraine patients with aura but also in those without aura during the attack-free period. PMID- 26276223 TI - Predisposing Factors for Spontaneous Closure of Congenital Portosystemic Shunts. AB - In a review of 382 cases of congenital portosystemic shunt, we found that presentation with neonatal cholestasis strongly predicts spontaneous closure of intrahepatic shunts (OR 8.3, 95% CI 3.4-20.2). Spontaneous closure before the 24th month of age is more likely for distal or multiple shunts, but rare for patent ductus venosus. PMID- 26276224 TI - Beyond Blame: Parents as Partners. PMID- 26276225 TI - Comparative proteomic analysis of hemolymph proteins from Autographa californica multiple nucleopolyhedrovirus (AcMNPV)-sensitive or -resistant silkworm strains during infections. AB - We reported previously that baculovirus AcMNPV host-ranges in silkworm strains are controlled by a novel third chromosomal locus. To further isolate the potential host factor and uncover the functional pathway involved, in this study we analyzed hemolymph proteins from AcMNPV-resistant or -sensitive silkworm strains infected with baculoviruses. All the protein spots from 2D electrophoresis were characterized by MALDI-TOF MS and further systematically assessed for differentially regulated proteins at different stages of infection. Subsequently, six candidates were selected for functional analysis using Bm5 cells, where the candidates were knocked-down or overexpressed. We observed that mRNA expression levels of beta-N-acetylglucosaminidase and prophenoloxidase subunit 2 are significantly upregulated during AcMNPV infections in Bm5 cells. Ultimately, we found that RNA interference of ribosomal protein RpL34 causes serious damages to cell viability as well as abortive infection, indicating that ribosomal components are essential for productive baculovirus infection. PMID- 26276226 TI - TET proteins in cancer: Current 'state of the art'. AB - Aberrations in DNA methylation patterns are observed from the early stages of carcinogenesis. However, the mechanisms that drive these changes remain elusive. The recent characterization of ten-eleven translocation (TET) enzymes as a source of newly modified cytosines (5-hydroxymethylcytosine, 5-formylcytosine and 5 carboxylcytosine) has shed new light on the DNA demethylation process. These cytosines are intermediates of an active DNA demethylation process and are epigenetic markers per se. In this review, we discuss the mechanism and function of TET proteins in biological processes as well as current knowledge regarding their expression and regulation in cancer. PMID- 26276227 TI - Mobile Exercise Apps and Increased Leisure Time Exercise Activity: A Moderated Mediation Analysis of the Role of Self-Efficacy and Barriers. AB - BACKGROUND: There are currently over 1000 exercise apps for mobile devices on the market. These apps employ a range of features, from tracking exercise activity to providing motivational messages. However, virtually nothing is known about whether exercise apps improve exercise levels and health outcomes and, if so, the mechanisms of these effects. OBJECTIVE: Our aim was to examine whether the use of exercise apps is associated with increased levels of exercise and improved health outcomes. We also develop a framework within which to understand how exercise apps may affect health and test multiple models of possible mechanisms of action and boundary conditions of these relationships. Within this framework, app use may increase physical activity by influencing variables such as self-efficacy and may help to overcome exercise barriers, leading to improved health outcomes such as lower body mass index (BMI). METHODS: In this study, 726 participants with one of three backgrounds were surveyed about their use of exercise apps and health: (1) those who never used exercise apps, (2) those who used exercise apps but discontinued use, and (3) those who are currently using exercise apps. Participants were asked about their long-term levels of exercise and about their levels of exercise during the previous week with the International Physical Activity Questionnaire (IPAQ). RESULTS: Nearly three-quarters of current app users reported being more active compared to under half of non-users and past users. The IPAQ showed that current users had higher total leisure time metabolic equivalent of task (MET) expenditures (1169 METs), including walking and vigorous exercise, compared to those who stopped using their apps (612 METs) or who never used apps (577 METs). Importantly, physical activity levels in domains other than leisure time activity were similar across the groups. The results also showed that current users had lower BMI (25.16) than past users (26.8) and non-users (26.9) and that this association was mediated by exercise levels and self efficacy. That relationship was also moderated by perceived barriers to exercise. Multiple serial mediation models were tested, which revealed that the association between app use and BMI is mediated by increased self-efficacy and increased exercise. CONCLUSIONS: Exercise app users are more likely to exercise during their leisure time, compared to those who do not use exercise apps, essentially fulfilling the role that many of these apps were designed to accomplish. Data also suggest that one way that exercise apps may increase exercise levels and health outcomes such as BMI is by making it easier for users to overcome barriers to exercise, leading to increased self-efficacy. We discuss ways of improving the effectiveness of apps by incorporating theory-driven approaches. We conclude that exercise apps can be viewed as intervention delivery systems consisting of features that help users overcome specific barriers. PMID- 26276230 TI - The importance of leadership in the cath lab. PMID- 26276229 TI - Ultrasound-guided procedures in medical education: a fresh look at cadavers. AB - Demand for bedside ultrasound in medicine has created a need for earlier exposure to ultrasound education during the clinical years of undergraduate medical education. Although bedside ultrasound is often used for invasive medical procedures, there is no standardized educational model for procedural skills that can provide the learner a real-life simulated experience. The objective of our study was to describe a unique fresh cadaver preparation model, and to determine the impact of a procedure-focused ultrasound training session. This study was a cross-sectional study at an urban academic medical center. A sixteen-item questionnaire was administered at the beginning and end of the session. Fifty five third year medical students participated in this 1-day event during their surgical clerkship. Students were trained to perform the following ultrasound guided procedures: internal jugular vein cannulation, femoral vein cannulation femoral artery cannulation and pericardiocentesis. Preparation of the fresh cadaver is easily replicated and requires minor manipulation of cadaver vessels and pericardial space. Fifty-five medical students in their third year participated in this study. All of the medical students agreed that US could help increase their confidence in performing procedures in the future. Eighty percent (95 % CI 70-91 %) of students felt that there was a benefit of learning ultrasound-based anatomy in addition to traditional methods. Student confidence was self-rated on a five-point Likert scale. Student confidence increased with statistical significance in all of the skills taught. The most dramatic increase was noted in central venous line placement, which improved from 1.95 (SD = 0.11) to 4.2 (SD = 0.09) (p < 0.001). The use of fresh cadavers for procedure-focused US education is a realistic method that improves the confidence of third year medical students in performing complex but critical procedures. PMID- 26276228 TI - Genotyping concordance in DNA extracted from formalin-fixed paraffin embedded (FFPE) breast tumor and whole blood for pharmacogenetic analyses. AB - BACKGROUND: Cancer pharmacogenetic studies use archival tumor samples as a DNA source when germline DNA is unavailable. Genotyping DNA from formalin-fixed paraffin embedded tumors (FFPE-T) may be inaccurate due to FFPE storage, genetic aberrations, and/or insufficient DNA extraction. Our objective was to assess the extent and source of genotyping inaccuracy from FFPE-T DNA and demonstrate analytical validity of FFPE-T genotyping of candidate single nucleotide polymorphisms (SNPs) for pharmacogenetic analyses. METHODS: Cancer pharmacogenetics SNPs were genotyped by Sequenom MassARRAYs in DNA harvested from matched FFPE-T, FFPE lymph node (FFPE-LN), and whole blood leukocyte samples obtained from breast cancer patients. No- and discordant-call rates were calculated for each tissue type and SNP. Analytical validity was defined as any SNP with <5% discordance between FFPE-T and blood and <10% discordance plus no calls. RESULTS: Matched samples from 114 patients were genotyped for 247 SNPs. No call rate in FFPE-T was greater than FFPE-LN and blood (4.3% vs. 3.0% vs. 0.5%, p < 0.001). Discordant-call rate between FFPE-T and blood was very low, but greater than that between FFPE-LN and blood (1.1% vs. 0.3%, p < 0.001). Samples with heterozygous genotypes were more likely to be no- or discordantly-called in either tissue (p < 0.001). Analytical validity of FFPE-T genotyping was demonstrated for 218 (88%) SNPs. CONCLUSIONS: No- and discordant-call rates were below concerning thresholds, confirming that most SNPs can be accurately genotyped from FFPE-T on our Sequenom platform. FFPE-T is a viable DNA source for prospective-retrospective pharmacogenetic analyses of clinical trial cohorts. PMID- 26276231 TI - Diabetes is not sufficient justification for IIb/IIIa use in percutaneous coronary intervention. AB - Diabetics, particularly insulin treated, have increased risk of ischemic events and bleeding with percutaneous coronary intervention (PCI). The relative risk of atherothrombotic versus bleeding events is higher in diabetics than non diabetics. Bivalirudin with provisional IIb/IIIa therapy has less bleeding and lower one-year mortality than routine IIb/IIIa therapy in diabetics undergoing PCI. IIb/IIIa agents should be reserved for provisional and niche applications during PCI. PMID- 26276232 TI - Bivalirudin: An expensive heparin? AB - Bleeding rates with unfractionated heparin (UH) without concomitant use of glycoprotein IIb/IIIa inhibitors as compared to bivalirudin are similar. Ischemic event rates during the index hospitalization are similar in the heparin and bivalirudin subgroups. Low does heparin (60-70 units/kg) with a target ACT of 200 250 sec may obviate the historical improved safety of bivalirudin demonstrated in certain clinical trials. PMID- 26276233 TI - Coronary perforation: What color is your parachute? AB - Coronary perforation is a rare but devastating complication of PCI, requiring rescue devices such as covered stents. This paper documents the successful use of a pericardial covered stent in 9/9 patients for coronary perforation. Pericardial covered stents have theoretical advantages over PTFE covered stents, but clinical studies proving this are not feasible. PMID- 26276234 TI - Pop goes the PA! and the aorta! iatrogenic aortopulmonary connections. AB - Iatrogenic aortopulmonary connections may occur after pulmonary artery angioplasty, stent or trans-catheter pulmonary valve implantation Patients with Ross autograft or arterial switch procedure may be at particular risk for this complication Timely diagnosis is facilitated by post-intervention aortic angiogram. PMID- 26276235 TI - Carotid artery stenting: Optimizing patient selection and technique. AB - Complex arch anatomy (type 2, type 3) and bovine configuration were identified in 34.4% and 20.5% of carotid stent patients, respectively. Catheter manipulation time (CMT), rather than arch complexity per se, was the only independent predictor of adverse events after carotid stenting. Careful attention to patient selection, preprocedural planning, and stent technique are important to ensure success. PMID- 26276236 TI - Treating on the edge. AB - Treatment of stent graft edge restenosis can be successfully treated but optimal treatment has not been identified. The practice of continued duplex surveillance for stent grafts appears to be important. Randomized trials comparing drug technology and to properly sized stent graft extension will be needed. PMID- 26276237 TI - Cutting down on the cutdown: Time to remove the training wheels for transfemoral access for TAVR. AB - Percutaneous transfemoral access is replacing cutdowns, even in the absence of a high level evidence base The evolution of smaller profile TAVR sheaths will make cutdowns largely obsolete Patient comfort, early ambulation, and shorter length of stay, along with improved methodologies will continue to drive the move to percutaneous access and closure for TAVR. PMID- 26276238 TI - A single degree of oversize does not fit all valve types. AB - Moderate valve oversize increases the risk of aortic regurgitation with self expandable valves, and larger oversizing may be preferable with this valve type. Large oversizing increases the risk of aortic annular rupture in patients treated with balloon-expandable valves and less oversizing appears safer. Anatomical factors may also may influence procedural success and should not be overlooked. PMID- 26276240 TI - Cardiovascular safety of albiglutide in the Harmony programme: a meta-analysis. AB - BACKGROUND: Albiglutide is a glucagon-like peptide-1 receptor agonist, a new class of drugs used to treat type 2 diabetes. We did a prospective meta-analysis of the cardiovascular safety of albiglutide as stipulated by the US Food and Drug Administration recommendations for the assessment of new treatments for diabetes. METHODS: We did a meta-analysis of eight phase 3 trials and one phase 2b trial in which patients were randomly assigned to albiglutide, placebo, or active comparators (glimepiride, insulin glargine, insulin lispro, liraglutide, pioglitazone, or sitagliptin). The safety population included 5107 patients, of whom 2524 took albiglutide (4870 person-years) and 2583 took comparators (5213 person-years). Possible major cardiovascular events were recorded prospectively and adjudicated by an independent endpoint committee masked to treatment allocation. The primary endpoint was a composite of first occurrence of major adverse cardiovascular events (ie, cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) or hospital admission for unstable angina. Secondary endpoints were major adverse cardiovascular events alone, all-cause mortality, silent myocardial infarction, hospital admission for heart failure, chest pain, other angina, and subdural or extradural haemorrhage. The occurrence of all other adverse events classified by the investigators as cardiovascular events were documented, but these were not adjudicated. FINDINGS: The primary endpoint was not significantly different between albiglutide and all comparators (58 events vs 58 events; hazard ratio [HR] 1.00, 95% CI 0.68-1.49, p=0.0019 for non-inferiority). Major adverse cardiovascular event alone was also not significantly different (52 events vs 53; HR, 0.99; 95% CI, 0.65-1.49). When albiglutide was compared separately with placebo or active comparators, we noted no significant differences. We detected no significant differences in the other secondary endpoints. More patients had atrial fibrillation or atrial flutter in the albiglutide group (35 [1.4%] of 2524 patients; 8.6 events per 1000 patient years) than in the all-comparators group (16 [0.6%] of 2583 patients; 3.4 events per 1000 patient-years). INTERPRETATION: Cardiovascular events were not significantly more likely to occur with albiglutide than with all comparators. Because the upper bound of the 95% CI for major adverse cardiovascular event plus hospital admission for unstable angina was greater than 1.3, a dedicated study with a cardiovascular endpoint is underway to confirm the safety of albiglutide. FUNDING: GlaxoSmithKline. PMID- 26276241 TI - Cardiovascular safety of albiglutide and other glucagon-like peptide-1 receptor agonists. PMID- 26276243 TI - Langerhans cell histiocytosis of the cervical spine. PMID- 26276244 TI - Unusual cause of lumbar instability in a posttraumatic patient: bilateral pedicle fractures. PMID- 26276245 TI - A definition of modern contraceptive methods. PMID- 26276246 TI - Meaning-making matters in product design: users' sensory perceptions and experience evaluations of long-acting vaginal gels and intravaginal rings. AB - OBJECTIVE: Users' sensory perceptions and experiences of intravaginal products can inform acceptability and adherence. Focusing on the meanings women derive from formulation/device characteristics facilitates developers' design iterations toward optimizing user experience. We investigated how users of long-acting gels and intravaginal rings (IVRs) impute meaning to characteristics that may affect future product use. STUDY DESIGN: Focus groups were conducted with contraceptive IVR and vaginal lubricant users. Current perceptibility science and historical theory on the cultural acceptability of fertility regulating methods informed the analysis. RESULTS: A total of 21 IVR users and 29 lubricant users attended focus groups in which they manipulated products in their hands and discussed reactions to product characteristics. Participants used prior product experiences and sensory perceptions of prototype manipulations to inform meanings about product properties and performance for pregnancy, disease prevention, comfort, and perceived efficacy. The meanings derived from product characteristics depended on why the product would be used; a characteristic deemed problematic in one risk context may be considered preferable in another. CONCLUSIONS: Intravaginal product users create narratives that ascribe influence or causality to product characteristics. These meanings, whether correct or incorrect biologically, will shape vaginal product acceptability, use, and effectiveness. IMPLICATIONS: Long acting and sustained-release drug delivery systems will be part of the multipurpose prevention continuum. Developers must consider how sensory experiences and culturally salient assumptions shape the meanings users make of product design characteristics. Those meanings will ultimately impact use and effectiveness. PMID- 26276247 TI - Association between retinal vasculature and muscle mass in older people. AB - Sarcopenia in older people is a major health issue and its early detection could help target interventions and improve health. Evidence suggests that poor muscle mass is associated with greater arterial stiffness and cardiovascular risk. Arterial stiffness in turn is associated with smaller retinal artery width. This study examined the association of muscle mass in older people with retinal vascular width, a non-invasive measure of vascular function. METHODS: Participants >65 years were recruited to a cross-sectional study. EXCLUSIONS: Inability to walk independently; diabetes mellitus; stroke (within 6 months), severe macular degeneration, glaucoma, retinal dystrophy; advanced cataract. Digital Retinal images of both eyes were analysed using the VAMPIRE software suite. Central Retinal Artery and Vein Equivalents (CRVE and CRAE) were measured. Body composition was measured using Dual Energy X ray Absorptimetry (DXA). Appendicular Skeletal Muscle Mass/Height(2) was calculated. Physical function was measured: 6-min walk distance, Short Physical performance battery, handgrip strength and quadriceps strength. RESULTS: 79 participants with mean age 72 (SD 6) years were recruited. 44% were female. Digital Retinal images of sufficient quality for measuring CRAE and CRVE were available for 51/75 (68%) of participants. Regression analysis showed significant association between larger ASMM/H(2) and smaller CRAE (beta=-0.20, p=0.001) and CRVE (beta=-0.12, p=0.05). Handgrip strength, body mass index and sex combined with CRAE explained 88% and with CRVE explained 86% of the variance in ASMM/H(2). CONCLUSION: Larger muscle mass was significantly associated with smaller retinal artery size in older people. This unexpected finding needs further investigation. PMID- 26276248 TI - Recurrent frontal tumour in a patient with repeated craniotomies. PMID- 26276249 TI - Cross-cultural adaptation of the Malay version of the child self-report Health related Quality of Life Measure for Children with Epilepsy (CHEQOL-25) in Malaysia. PMID- 26276250 TI - LORETA indicates frequency-specific suppressions of current sources within the cerebrums of blindfolded subjects from patterns of blue light flashes applied over the skull. AB - An array of eight cloistered (completely covered) 470-nm LEDs was attached to the right caudal scalp of subjects while each sat blindfolded within a darkened chamber. The LEDs were activated by a computer-generated complex (frequency modulated) temporal pattern that, when applied as weak magnetic fields, has elicited sensed presences and changes in LORETA (low-resolution electromagnetic tomography) configurations. Serial 5-min on to 5-min off presentations of the blue light (10,000lx) resulted in suppression of gamma activity within the right cuneus (including the extrastriate area), beta activity within the left angular and right superior temporal regions, and alpha power within the right parahippocampal region. The effect required about 5min to emerge followed by a transient asymptote for about 15 to 20min when diminished current source density was evident even during no light conditions. Subjective experiences, as measured by our standard exit questionnaire, reflected sensations similar to those reported when the pattern was presented as a weak magnetic field. Given previous evidence that photon flux density of this magnitude can penetrate the skull, these results suggest that properly configured LEDs that generate physiologically patterned light sequences might be employed as noninvasive methods to explore the dynamic characteristics of cerebral activity in epileptic and nonepileptic brains. PMID- 26276252 TI - Added release time in diffusion/dissolution coupled release. AB - While increasingly sophisticated models have been developed to more accurately predict dispersed solute release from complex systems, distillation of their results into quantitative trends has been difficult. Here, the numerically calculated release profiles of coupled diffusion/dissolution systems are quantified by their cumulative release time (CRT) and compared against corresponding diffusion-controlled limits. The increase in CRT due to a finite dissolution rate was found to vary inversely with the second Damkohler number across several orders of magnitude, and also vary linearly with the amount of solid drug loaded in the system. The analytical nature of the relationship provides new physical insights into the system and appears to be indifferent to the form of the secondary rate-limiting step. This work provides a simple analytical expression with which one can not only predict the mean release time for a given set of parameter values, but understand precisely how each parameter value will affect it. The simplicity of the correlation and the lack of apparent limits to its validity also suggest the existence of an analytical pathway for its derivation, which may yield additional insights into the effect of secondary rate processes on controlled release. PMID- 26276253 TI - In-vivo evaluation of clindamycin release from glyceryl monooleate-alginate microspheres by NIR spectroscopy. AB - The purpose of this study was to use near-infrared (NIR) transmission spectroscopic technique to determine clindamycin plasma concentration after oral administration of clindamycin loaded GMO-alginate microspheres using rabbits as animal models. Lyophilized clindamycin-plasma standard samples at a concentration range of 0.001-10 MUg/ml were prepared and analyzed by NIR and HPLC as a reference method. NIR calibration model was developed with partial least square (PLS) regression analysis. Then, a single dose in-vivo evaluation was carried out and clindamycin-plasma concentration was estimated by NIR. Over 24 h time period, the pharmacokinetic parameters of clindamycin were calculated for the clindamycin loaded GMO-alginate microspheres (F3) and alginate microspheres (F2), and compared with the plain drug (F1). PLS calibration model with 7-principal components (PC), and 8000-9200 cm(-1) spectral range shows a good correlation between HPLC and NIR values with root mean square error of cross validation (RMSECV), root mean square error of prediction (RMSEP), and calibration coefficient (R(2)) values of 0.245, 1.164, and 0.9753, respectively, which suggests that NIR transmission technique can be used for drug-plasma analysis without any extraction procedure. F3 microspheres exhibited controlled and prolonged absorption Tmax of 4.0 vs. 1.0 and 0.5 h; Cmax of 2.37+/-0.3 vs. 3.81+/ 0.8 and 5.43+/-0.7 MUg/ml for F2 and F1, respectively. These results suggest that the combination of GMO and alginate (1:4 w/w) could be successfully employed for once daily clindamycin microspheres formulation which confirmed by low Cmax and high Tmax values. PMID- 26276254 TI - In vitro model of infected stratum corneum for the efficacy evaluation of poloxamer 407-based formulations of ciclopirox olamine against Trichophyton rubrum as well as differential scanning calorimetry and stability studies. AB - Superficial fungal skin infections are a common disease and concern 20-25% of the world's population with the dermatophyte Trichophyton rubrum being the main trigger. Due to autoinoculation, fungal skin infections of the feet (tinea pedis) often occur simultaneously with fungal nail infections (onychomycosis). Therefore, the overall objective was the development and characterisation of poloxamer 407-based formulations with the antimycotic active ingredient ciclopirox olamine (CPX) for simultaneous antifungal therapy. The formulations consisted of poloxamer 407, water, isopropyl alcohol, propylene glycol and medium chain triglycerides in given ratios. The in vitro antifungal efficacy against T. rubrum was tested in a novel in vitro model of infected stratum corneum in comparison to a marketed semi-solid formulation containing 1% (w/w) ciclopirox olamine and a marketed nail lacquer containing 8% ciclopirox. Several liquid poloxamer 407-based formulations with only 1% CPX completely inhibited fungal growth after 6 days of incubation, whereas the marketed semi-solid formulation did not inhibit fungal growth. Differential scanning calorimetry studies revealing the interaction between the formulations and the SC showed that increasing isopropyl alcohol/propylene glycol concentrations as well as increasing CPX concentrations caused increasing endothermic transition shifts. Moreover, stability studies at 30 degrees C exhibited only a slight decrease of the CPX amount after 12 months of storage. Each formulation contained >90% of the initial CPX concentration after termination of the stability studies. PMID- 26276255 TI - Impact of acoustic airflow on intrasinus drug deposition: New insights into the vibrating mode and the optimal acoustic frequency to enhance the delivery of nebulized antibiotic. AB - AIM: We investigated the impact of vibrating acoustic airflow, the high frequency (f>=100 Hz) and the low frequency (f<=45 Hz) sound waves, on the enhancement of intrasinus drug deposition. METHODS: (81m)Kr-gas ventilation study was performed in a plastinated human cast with and without the addition of vibrating acoustic airflow. Similarly, intrasinus drug deposition in a nasal replica using gentamicin as a marker was studied with and without the superposition of different modes of acoustic airflow. RESULTS: Ventilation experiments demonstrate that no sinus ventilation was observed without acoustic airflow although sinus ventilation occurred whatever the modes of acoustic airflow applied. Intrasinus drug deposition experiments showed that the high frequency acoustic airflow led to 4-fold increase in gentamicin deposition into the left maxillary sinus and to 2-fold deposition increase into the right maxillary sinus. Besides, the low frequency acoustic airflow demonstrated a significant increase of 4-fold and 2 fold in the right and left maxillary sinuses, respectively. CONCLUSION: We demonstrated the benefit of different modes of vibrating acoustic airflow for maxillary sinus ventilation and intrasinus drug deposition. The degree of gentamicin deposition varies as a function of frequency of the vibrating acoustic airflow and the geometry of the ostia. PMID- 26276256 TI - Matrix effects in nilotinib formulations with pH-responsive polymer produced by carbon dioxide-mediated precipitation. AB - Factors determining the pH-controlled dissolution kinetics of nilotinib formulations with the pH-titrable polymer hydroxypropyl methylcellulose phthalate, obtained by carbon dioxide-mediated precipitation, were mechanistically examined in acid and neutral environment. The matrix effect, modulating the drug dissolution, was characterized with a battery of physicochemical methodologies, including ToF-SIMS for surface composition, SAXS/WAXS and modulated DSC for crystallization characterization, and simultaneous UV-imaging and Raman spectroscopy for monitoring the dissolution process in detail. The hybrid particle formulations investigated consisted of amorphous nilotinib embedded in a polymer matrix in single continuous phase, displaying extended retained amorphicity also under wet conditions. It was demonstrated by Raman and FTIR spectroscopy that the efficient drug dispersion and amorphization in the polymer matrix were mediated by hydrogen bonding between the drug and the phthalate groups on the polymer. Simultaneous Raman and UV imaging studies of the effect of drug load on the swelling and dissolution of the polymer matrix revealed that high nilotinib load prevented matrix swelling on passage from acid to neutral pH, thereby preventing re-precipitation and re crystallization of incorporated nilotinib. These findings provide a mechanistic foundation of formulation development of nilotinib and other protein kinase inhibitors, which are now witnessing an intense therapeutic and industrial attention due to the difficulty in formulating these compounds so that efficient oral bioavailability is reached. PMID- 26276257 TI - Biomimetic estimation of glucose using non-molecular and molecular imprinted polymer nanosponges. AB - The aim of the present work was to develop biomimetics for glucose estimation using molecularly and non-molecularly imprinted polymers of pyromellitic dianhydride crosslinked beta-cyclodextrin based nanosponges. The ionic association of glucose phosphate to nanosponges by polymerization reaction and removal of glucose created molecular imprinted polymer (MIP)-nanosponges with affinity for glucose binding. Particle size, zeta potential, glucose binding studies and FTIR were used to characterize molecular and non-molecular imprinted polymer (NIP) nanosponges. Particle size of the nanosponges was found in the range of 450.81+/-5.33 nm to 550.63+/-8.14 nm with low polydispersity index. MIP nanosponges retained a relatively large population of pores in the nano-range, while NIP was related to the nonporous materials with weak interaction and had poor tendency to aggregate. Nanosponges showed the variation in binding capacities and specificities; and also exhibited a similar degree of swelling. Moreover electrostatic force of attraction and cavities specific fitting of glucose in MIP-nanosponges might be due to advance selectivity and affinity for glucose. FTIR study showed glucose molecules might be entered into the selective binding cavities, which were created by the extraction of template molecules It is concluded that nanosized MIP-nanosponges have advantages over conventional NIP due to diffusion of template in the formed cavity as of its high surface area. PMID- 26276258 TI - Pectin/anhydrous dibasic calcium phosphate matrix tablets for in vitro controlled release of water-soluble drug. AB - Different pectin/anhydrous dibasic calcium phosphate (ADCP) matrix tablets have been developed in order to obtain controlled release of a water-soluble drug (theophylline). Swelling, buoyancy and dissolution studies have been carried out in different aqueous media (demineralized water, progressive pH medium, simulated gastric fluid, simulated intestinal fluid and simulated colonic fluid), to characterize the matrix tablets. When the pectin/ADCP ratio was >=0.26 (P1, P2, P3 and P4 tablets) a continuous swelling and low theophylline dissolution rate from the matrices were observed. So, pectin gel forming feature predominated over the ADCP properties, yielding pH-independent drug release behavior from these matrices. On the contrary, pectin/ADCP ratios <=0.11 (P5 and P6 tablets) allowed to achieve drug dissolution pH dependent. Consequently, the suitable selection of the pectin/ADCP ratio will allow to tailor matrix tablets for controlled release of water-soluble drugs in a specific manner in the gastrointestinal tract. PMID- 26276259 TI - Optimization of pH-independent chronotherapeutic release of verapamil HCl from three-layer matrix tablets. AB - The aim of this work was to evaluate and optimize formulation of three-layer matrix tablets based on xanthan gum (XG) and sodium alginate for chronotherapeutic pH-independent release of verapamil HCl (VH). Artificial neural networks (ANN) were applied in the optimization and compared with multiple linear regression (MLR). A face-centered central composite experimental design was employed with three factors (mass fraction of VH in intermediate layer, X1, and of XG in matrix former of intermediate and outer layers, X2 and X3). The prepared tablets were tested for in vitro release in 0.1 N HCl and phosphate buffer (pH 7.5), tensile strength and friability. Furthermore, swelling observation and release modeling to Weibull function and power law equation of Peppas were employed to help further understanding of release behavior and mechanism. The releases (%) in phosphate buffer (pH 7.5) at 6, 12 and 24 h were selected as responses to depict the mode of release and similarity factor (f2), between release profiles in 0.1N HCl and pH 7.5 during the first 8 h, as response of pH independence. A desirability function combining the four responses was constructed and overall desirability values were used for the ANN and MLR modeling. Five additional checkpoint formulations, within the experimental domain, were used to validate the external predictability of the models. The constructed ANN model fitted better to the overall desirability than the MLR model (R=0.838 vs. 0.670, for the additional checkpoint formulations) and therefore, was used for prediction of formulation with optimal in vitro drug release. PMID- 26276260 TI - Hypocomplementemic urticarial vasculitis arising in a patient with immunoglobulin G4-related disease. AB - BACKGROUND: Hypocomplementemic urticarial vasculitis (HUV) has been defined as a syndrome associated with urticarial lesions caused by leukocytoclastic vasculitis. It has been observed in patients with systemic lupus erythematosus and related conditions. Immunoglobulin G4 (IgG4)-related disease is a lymphoproliferative disorder characterized by sclerosing pancreatitis, retroperitoneal fibrosis, sclerotic cholangitis, acute interstitial nephritis, and Mikulicz's disease, and associated with elevated levels of IgG4 and hypocomplementemia. Various cutaneous lesions may occur in IgG4-related disease. METHODS: We report a 74-year-old woman with HUV, followed by systemic organ involvement suggestive of IgG4-related disease. Symptoms included submandibular gland swelling, lymphadenopathy, interstitial nephritis, and a thyroid nodule. Laboratory examinations revealed an elevated serum IgG4 level of 637 mg/dl in a total IgG level of 2176 mg/dl, and the production of autoantibodies such as rheumatoid factor and antiphospholipid antibodies. In the swollen lymph node, neither clonal proliferation of T or B cells nor Epstein-Barr virus infection was detected, although the structure had been destroyed by the infiltration of lymphocytes and plasma cells. Among total IgG-producing cells, approximately 40% were positive for IgG4. RESULTS: All symptoms and abnormal laboratory findings improved in response to oral prednisolone. CONCLUSIONS: Hypocomplementemic urticarial vasculitis may represent a clinical symptom of IgG4-related disease. PMID- 26276261 TI - Discovery and verification of serum differential expression proteins for pulmonary tuberculosis. AB - Pulmonary tuberculosis (PTB) is a chronic disease and has remained a severe threat to public health. Valuable biomarkers for improving the detection rate are crucial for controlling this disease. The purpose of this study was to discover potential biomarkers in sera from PTB patients compared with pneumonia patients and normal healthy controls. A total of 336 human serum specimens were enrolled in this study. Differentially expressed proteins were identified using iTRAQ method combining with MALDI-TOF-MS. Data was analyzed using relative bioinformatics methods. Potential biomarkers were further validated by IHC, ELISA and Western blot. As a result, 489 non-redundant proteins were identified in the sera, and 159 of which could be quantified by calculating their iTRAQ ratios. Compared to the controls, 26 differentially expressed proteins were recognized among PTB patients, including 16 overexpressed proteins and 10 downregulated proteins. Analysis of their functional interactions revealed that 12 proteins appeared in the center of the functional network. One of these key proteins, sex hormone binding globulin (SHBG), was found to be significantly elevated among PTB patients as compared with the controls examined by IHC, ELISA and Western blot. This result was consistent with the iTRAQ result. An independent blinded testing set to examine serum SHBG by ELISA achieved an accuracy of 78.74%, sensitivity of 75.6% and specificity of 91.5% in diagnosing PTB. In summary, iTRAQ in combination with MALDI-TOF-MS technology can efficiently screen differentially expressed proteins in sera from the PTB patients. SHBG is suggested to be a possible and novel serum biomarker for PTB. PMID- 26276262 TI - Insulin resistance is associated with poorer verbal fluency performance in women. AB - AIMS/HYPOTHESIS: Type 2 diabetes is an independent risk factor for cognitive decline. Insulin resistance occurring during midlife may increase the risk of cognitive decline later in life. We hypothesised that insulin resistance is associated with poorer cognitive performance and that sex and APOE*E4 might modulate this association. METHODS: The association of insulin resistance and APOE*E4 genotype on cognitive function was evaluated in a nationwide Finnish population-based study (n = 5,935, mean age 52.5 years, range 30-97 years). HOMA IR was used to measure insulin resistance. Cognitive function was tested by word list learning, word-list delayed-recall, categorical verbal fluency and simple and visual-choice reaction-time tests. Linear regression analysis was used to determine the association between HOMA-IR and the results of the cognitive tests. RESULTS: Higher HOMA-IR was associated with poorer verbal fluency in women (p < 0.0001) but not in men (p = 0.56). Higher HOMA-IR was also associated with poorer verbal fluency in APOE*E4 -negative individuals (p = 0.0003), but not in APOE*E4 carriers (p = 0.28). Furthermore, higher HOMA-IR was associated with a slower simple reaction time in the whole study group (p = 0.02). CONCLUSIONS/INTERPRETATION: To our knowledge, this is the first comprehensive, population-based study, including both young and middle-aged adults, to report that female sex impacts the association of HOMA-IR with verbal fluency. Our study was cross-sectional, so causal effects of HOMA-IR on cognition could not be evaluated. However, our results suggest that HOMA-IR could be an early marker for an increased risk of cognitive decline in women. PMID- 26276263 TI - Mast cells infiltrate pancreatic islets in human type 1 diabetes. AB - AIMS/HYPOTHESIS: Beta cell destruction in human type 1 diabetes occurs through the interplay of genetic and environmental factors, and is mediated by immune cell infiltration of pancreatic islets. In this study, we explored the role of mast cells as an additional agent in the pathogenesis of type 1 diabetes insulitis. METHODS: Pancreatic tissue from donors without diabetes and with type 1 and 2 diabetes was studied using different microscopy techniques to identify islet-infiltrating cells. The direct effects of histamine exposure on isolated human islets and INS-1E cells were assessed using cell-survival studies and molecular mechanisms. RESULTS: A larger number of mast cells were found to infiltrate pancreatic islets in samples from donors with type 1 diabetes, compared with those from donors without diabetes or with type 2 diabetes. Evidence of mast cell degranulation was observed, and the extent of the infiltration correlated with beta cell damage. Histamine, an amine that is found at high levels in mast cells, directly contributed to beta cell death in isolated human islets and INS-1E cells via a caspase-independent pathway. CONCLUSIONS/INTERPRETATION: These findings suggest that mast cells might be responsible, at least in part, for immune-mediated beta cell alterations in human type 1 diabetes. If this is the case, inhibition of mast cell activation and degranulation might act to protect beta cells in individuals with type 1 diabetes. PMID- 26276265 TI - It's not just my fault: Neural correlates of feedback processing in solo and joint action. AB - People often coordinate their actions with others' in pursuit of shared goals, yet little research has examined the neural processes by which people monitor whether shared goals have been achieved. The current study compared event-related potentials elicited by feedback indicating joint errors (resulting from two people's coordinated actions) and individual errors (resulting from one's own or another person's observed actions). Joint errors elicited a reduced feedback related negativity (FRN) and P3a relative to own errors, and an enhanced FRN relative to observed errors. In contrast, P3b amplitudes did not differ between joint and individual errors. These findings indicate that producing errors together with a partner influences neural activity related to outcome evaluation but has less impact on activity related to the motivation to adapt future behaviour. PMID- 26276264 TI - Trends and patterns in the use of computed tomography in children and young adults in Catalonia - results from the EPI-CT study. AB - BACKGROUND: Although there are undeniable diagnostic benefits of CT scanning, its increasing use in paediatric radiology has become a topic of concern regarding patient radioprotection. OBJECTIVE: To assess the rate of CT scanning in Catalonia, Spain, among patients younger than 21 years old at the scan time. MATERIALS AND METHODS: This is a sub-study of a larger international cohort study (EPI-CT, the International pediatric CT scan study). Data were retrieved from the radiological information systems (RIS) of eight hospitals in Catalonia since the implementation of digital registration (between 1991 and 2010) until 2013. RESULTS: The absolute number of CT scans annually increased 4.5% between 1991 and 2013, which was less accentuated when RIS was implemented in most hospitals. Because the population attending the hospitals also increased, however, the rate of scanned patients changed little (8.3 to 9.4 per 1,000 population). The proportions of patients with more than one CT and more than three CTs showed a 1.51- and 2.7-fold increase, respectively, over the 23 years. CONCLUSION: Gradual increases in numbers of examinations and scanned patients were observed in Catalonia, potentially explained by new CT scanning indications and increases in the availability of scanners, the number of scans per patient and the size of the attended population. PMID- 26276266 TI - Does Faux Pas Detection in Adult Autism Reflect Differences in Social Cognition or Decision-Making Abilities? AB - 43 typically-developed adults and 35 adults with ASD performed a cartoon faux pas test. Adults with ASD apparently over-detected faux pas despite good comprehension abilities, and were generally slower at responding. Signal detection analysis demonstrated that the ASD participants had significantly greater difficulty detecting whether a cartoon depicted a faux pas and showed a liberal response bias. Test item analysis demonstrated that the ASD group were not in agreement with a reference control group (n = 69) about which non-faux pas items were most difficult. These results suggest that the participants with ASD had a primary problem with faux pas detection, but that there is another factor at work, possibly compensatory, that relates to their choice of a liberal response criterion. PMID- 26276267 TI - Analysis of expression patterns of IGF-1, caspase-3 and HSP-70 in developing human tooth germs. AB - AIMS: To analyze expression patterns of IGF-1, caspase-3 and HSP-70 in human incisor and canine tooth germs during the late bud, cap and bell stages of odontogenesis. MATERIALS AND METHODS: Head areas or parts of jaw containing teeth from 10 human fetuses aged between 9th and 20th developmental weeks were immunohistochemically analyzed using IGF-1, active caspase-3 and HSP-70 markers. Semi-quantitative analysis of each marker's expression pattern was also performed. RESULTS: During the analyzed period, IGF-1 and HSP-70 were mostly expressed in enamel organ. As development progressed, expression of IGF-1 and HSP 70 became more confined to differentiating tissues in the future cusp tip area, as well as in highly proliferating cervical loops. Few apoptotic bodies highly positive to active caspase-3 were observed in enamel organ and dental papilla from the cap stage onward. However, both enamel epithelia moderately expressed active caspase-3 throughout the investigated period. CONCLUSIONS: Expression patterns of IGF-1, active caspase-3 and HSP-70 imply importance of these factors for early human tooth development. IGF-1 and HSP-70 have versatile functions in control of proliferation, differentiation and anti-apoptotic protection of epithelial parts of human enamel organ. Active caspase-3 is partially involved in formation and apoptotic removal of primary enamel knot, although present findings might reflect its ability to perform other non-death functions such as differentiation of hard dental tissues secreting cells and guidance of ingrowth of proliferating cervical loops. PMID- 26276268 TI - Stages in third molar development and eruption to estimate the 18-year threshold Malay juvenile. AB - Age 18 years is considered as the age of majority by most countries. To ascertain the age of interest, both third molar development (TMD) and eruption (TME) staging scores are beneficial without needing multiple imaging modalities. This study aimed to assess the chronological course of TMD and TME in a Malay sub adult population and evaluate predictions when specific stage(s) of TMD and TME have been attained that are pertinent to the age group of interest (<18 years or >=18 years). A sample of 714 digital panoramic images for subjects stratified by age between 14.1 and 23.9 years was retrospectively collected. The techniques described by Gleiser and Hunt (modified by Kohler) and Olze were employed to stage TMD and TME, respectively. A binary logistic regression was performed to predict the 18-year threshold with staging score as predictors. Stages 4-6 (TMD) and A-B (TME) for males and stages 4 (TMD) and A (TME) for females were found to discriminate the <18-year group. For both genders, stages 9-10 (TMD) and D (TME) can be used as reference stages to estimate whether a subject is likely to be >=18 years, with 94.74-100% and 85.88-96.38% correct predictions, respectively. Stages 4 (TMD) and A (TME) can also be used to identify juveniles (<18 years) with a high degree of correct predictions, 100%. The juvenility of an individual is easily anticipated by using the specific staging scores of both third molar variables (TMD and TME) without complex calculations. PMID- 26276269 TI - Immunohistochemical expression of CD56 in dog (Canis familiaris) odontogenesis. AB - AIM: To investigate the expression of CD56 in dog odontogenesis in order to elucidate the expression found in ameloblastomas. MATERIALS AND METHODS: Immunohistochemical analysis of CD56 expression of developing dog teeth in the bud, cap and bell stages including the remnants of the dental lamina. RESULTS: Weak CD56 expression was observed in the dental epithelium during the bud stage with intense staining of certain peripheral epithelial cells. Positive staining of epithelial cells was also observed in the cap stage with intense staining of the inner enamel epithelium at this stage. During the bell stage the staining was concentrated on the cervical loop areas. The dental papilla revealed positive staining throughout the cap and bell stages while the dental follicle stained intensely positive throughout all the phases examined. The dental lamina and Serres rests also stained positive for CD56. CONCLUSIONS: The expression of CD56 in dog odontogenic tissue varies according to the stage of tooth development. There is a positive correlation between the positive staining observed in ameloblastomas and their odontogenic cells of origin. PMID- 26276270 TI - Potential role of differentially expressed lncRNAs in the pathogenesis of oral squamous cell carcinoma. AB - Long non-coding RNAs (lncRNAs) have recently attracted more attention about the role in a broad range of biological processes and complex cancers. We aimed to identify differentially expressed lncRNAs that play an important role in the pathogenesis of oral squamous cell carcinoma (OSCC). Microarray data GSE25099 consisting of 57 samples from patients with OSCC and 22 normal samples were downloaded from Gene Expression Omnibus database. Differentially expressed genes (DEGs) and lncRNAs were identified between OSCC samples and control using samr package in R and noncoder software. Co-expression network was constructed for lncRNAs and candidate target DEGs, followed by functional and pathway enrichment analysis using the Database for Annotation, Visualization and Integrated Discovery online tool. OSCC-related genes were screened by Genetic-Association-DB Database analysis, and then protein-protein interaction (PPI) network construction of OSCC-related and co-expressed genes. Bioinformatic analysis revealed that there were 998 DEGs and 160 differentially expressed lncRNAs between OSCC and normal control. We found LOC100130547, FTH1P3, PDIA3F and GTF2IRD2P1 targeted most of DEGs. Predicted targets-related functional annotation showed significant changes in inflammation-related functions and Toll-like receptor signaling pathway. By further conducting PPI network with lncRNA co expressed DEGs, we found that OSCC-associated genes including MMP1 (matrix metallopeptidase), MMP3, MMP9, PLAU (plasminogen activator, urokinase) and IL8 (interleukin 8) were targeted by FTH1P3, PDIA3F and GTF2IRD2P1. Our results indicate that lncRNAs FTH1P3, PDIA3F and GTF2IRD2P1 may responsible for progression and metastasis of OSCC via targeting MMP1, MMP3, MMP9, PLAU and IL8 which are key regulators of tumorigenesis. PMID- 26276271 TI - The association between social capital and quality of life among type 2 diabetes patients in Anhui province, China: a cross-sectional study. AB - BACKGROUND: To investigate the association between social capital and quality of life among type 2 diabetes patients in Anhui province, China. METHODS: In a cross sectional study, 436 adults with type 2 diabetes were interviewed. The two domains of Quality of life, physical component summary (PCS) and mental component summary (MCS), were measured using the Short-Form Health Survey (SF-36). A modified instrument scale was used to measure cognitive and structural social capital. Multiple logistic regression models were used to assess the associations between social capital and quality of life, adjusting for social economic status and risk factors for health. RESULTS: 24.3 % of participants (106) were in poor PCS and 25.0 % (109) in poor MCS. The proportions of participants who had low cognitive and structural social capital were 47.0 % (205) and 64.4 % (281), respectively. Results of logistic regression models showed that cognitive social capital was positively associated with PCS (OR = 1.84; 95 % CI: 1.12, 3.02) and MCS (OR = 1.65; 95 % CI: 1.03, 2.66). However, the associations between structural social capital and PCS (OR = 0.80, 95 % CI: 0.48, 1.34) and MCS (OR = 0.62; 95 % CI: 0.38, 1.01) were not statistically significant. CONCLUSIONS: It is the first study in China to investigate associations between quality of life and social capital in type 2 diabetes. Findings document that cognitive social capital is associated with the quality of life of type 2 diabetes patients. Our study suggests that the social capital theory may provide a new approach to increase physical resources in diabetes prevention and control, especially in Low and Middle Income countries (LMICs). PMID- 26276272 TI - Impact of renal function deterioration on adverse events during anticoagulation therapy using non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. AB - Renal function is crucial for patients with non-valvular atrial fibrillation (NVAF) using non-vitamin K antagonist oral anticoagulants (NOAC). The incidence of renal function deterioration during anticoagulation therapy and its impact of adverse events are unknown. In 807 consecutive NVAF patients treated with NOAC and with estimated creatinine clearance (eCCr) >= 50 ml/min (mean age 68 +/- 11 years, mean CHADS2 score = 1.8 +/- 1.4, CHA2DS2-VASc score = 2.8 +/- 1.8, HAS BLED score = 1.7 +/- 1.1), we analyzed the time course of renal function and clinical outcomes, and compared these with the data of general Japanese inhabitants from the Suita Study (n = 2140). Of the 807 patients, 751 (93 %) maintained eCCr >= 50 ml/min (group A) whereas the remaining 56 (7 %) fell into the eCCr < 50 ml/min (group B) during the 382 +/- 288 days of follow-up. Multivariate logistic regression analysis revealed that advanced age, lower body weight, and congestive heart failure were independent predictors for renal function deterioration in patients with eCCr >= 50 ml/min at baseline. Major and/or minor bleedings were more commonly observed in group B than in group A (21 vs. 8 %; P = 0.0004). The CHADS2, CHA2DS2-VASc, and HAS-BLED scores were also significant predictors of renal function deterioration (P < 0.0001). The incidences of renal function deterioration were 1.4, 3.4, 10.5 and 11.7 % in patients with CHADS2 score of 0, 1, 2 and >=3, respectively. As to CHA2DS2-VASc score, renal function deterioration occurred in 0, 1.7, 9.8 and 15.0 % with a score of 0, 1-2, 3-4 and >=5, respectively. In the Suita Study of the general population, on the other hand, 122 of 2140 participants with eCCr >= 50 ml/min at baseline (5.7 %) fell into the eCCr < 50 ml/min during about 2 years. The incidence of renal function deterioration increased with the CHADS2 score in the general population as well as in our patients. Renal function deterioration was not uncommon and was associated with more frequent adverse events including major bleeding in NVAF patients with anticoagulation therapy. CHADS2, CHA2DS2-VASc, and HAS-BLED scores may be useful as an index of predicting renal function deterioration. PMID- 26276273 TI - Carbazole hydroxylation by the filamentous fungi of the Cunninghamella species. AB - Nitrogen heterocyclic compounds, especially carbazole, quinolone, and pyridine are common types of environmental pollutants. Carbazole has a toxic influence on living organisms, and the knowledge of its persistence and bioconversion in ecosystems is still not complete. There is an increasing interest in detoxification of hazardous xenobiotics by microorganisms. In this study, the ability of three filamentous fungi of the Cunninghamella species to eliminate carbazole was evaluated. The Cunninghamella elegans IM 1785/21Gp and Cunninghamella echinulata IM 2611 strains efficiently removed carbazole. The IM 1785/21Gp and IM 2611 strains converted 93 and 82 % of the initial concentration of the xenobiotic (200 mg L(-1)) after 120 h incubation. 2-Hydroxycarbazole was for the first time identified as a carbazole metabolite formed by the filamentous fungi of the Cunninghamella species. There was no increase in the toxicity of the postculture extracts toward Artemia franciscana. Moreover, we showed an influence of carbazole on the phospholipid composition of the cells of the tested filamentous fungi, which indicated its harmful effect on the fungal cell membrane. The most significant modification of phospholipid levels after the cultivation of filamentous fungi with the addition of carbazole was showed for IM 1785/21Gp strain. PMID- 26276274 TI - Pesticide authorization in the EU-environment unprotected? AB - Pesticides constitute an integral part of high-intensity European agriculture. Prior to their authorization, a highly elaborated environmental risk assessment is mandatory according to EU pesticide legislation, i.e., Regulation (EC) No. 1107/2009. However, no field data-based evaluation of the risk assessment outcome, i.e., the regulatory acceptable concentrations (RACs), and therefore of the overall protectiveness of EU pesticide regulations exists. We conducted here a comprehensive meta-analysis using peer-reviewed literature on agricultural insecticide concentrations in EU surface waters and evaluated associated risks using the RACs derived from official European pesticide registration documents. As a result, 44.7 % of the 1566 cases of measured insecticide concentrations (MICs) in EU surface waters exceeded their respective RACs. It follows that current EU pesticide regulations do not protect the aquatic environment and that insecticides threaten aquatic biodiversity. RAC exceedances were significantly higher for insecticides authorized using conservative tier-I RACs and for more recently developed insecticide classes, i.e., pyrethroids. In addition, we identified higher risks, e.g., for smaller surface waters that are specifically considered in the regulatory risk assessment schemes. We illustrate the shortcomings of the EU regulatory risk assessment using two case studies that contextualize the respective risk assessment outcomes to field exposure. Overall, our meta-analysis challenges the field relevance and protectiveness of the regulatory environmental risk assessment conducted for pesticide authorization in the EU and indicates that critical revisions of related pesticide regulations and effective mitigation measures are urgently needed to substantially reduce the environmental risks arising from agricultural insecticide use. PMID- 26276275 TI - UCP2- and non-UCP2-mediated electric current in eukaryotic cells exhibits different properties. AB - Using live eukaryotic cells, including cancer cells, MCF-7 and HCT-116, normal hepatocytes and red blood cells in anode and potassium ferricyanide in cathode of MFC could generate bio-based electric current. Electrons and protons generated from the metabolic reaction in both cytosol and mitochondria contributing to the leaking would mediate the generation of electric current. Both resveratrol (RVT) and 2,4-dinitrophenol (DNP) used to induce proton leak in mitochondria were found to promote electric current production in all cells except red blood cells without mitochondria. Proton leak might be important for electric current production by bringing the charge balance in cells to enhance the further electron leak. The induced electric current by RVT can be blocked by Genipin, an inhibitor of UCP2-mediated proton leak, while that induced by DNP cannot. RVT could reduce reactive oxygen species (ROS) level in cells better than that of DNP. In addition, RVT increased mitochondrial membrane potential (MMP), while DNP decreased it. Results highly suggested the existence of at least two types of electric current that showed different properties. They included UCP2-mediated and non-UCP2-mediated electric current. UCP2-mediated electric current exhibited higher reactive oxygen species (ROS) reduction effect per unit electric current production than that of non-UCP2-mediated electric current. Higher UCP2-mediated electric current observed in cancer cells might contribute to the mechanism of drug resistence. Correlation could not be established between electric current production with either ROS and MMP without distinguishing the types of electric current. PMID- 26276277 TI - Physiological responses in roots of the grapevine rootstock 140 Ruggeri subjected to Fe deficiency and Fe-heme nutrition. AB - Iron (Fe)-heme containing fertilizers can effectively prevent Fe deficiency. This paper aims to investigate root physiological responses after a short period of Fe heme nutrition and Fe deficiency under two pH conditions (with or without HEPES) in the Fe chlorosis-tolerant grapevine rootstock 140 Ruggeri. Organic acids in root exudates, Fe reduction capacity, both roots and root exudates contributions, together with other physiological parameters associated to plant Fe status were evaluated in plants grown in hydroponics. Analyses of root tips by SEM, and Raman and IR spectra of the precipitates of Fe-heme fertilizers were performed. The physiological responses adopted by the tolerant 140 Ruggeri to the application of Fe-heme indicated an increased Fe reduction capacity of the roots. This is the first report showing oxalic, tartaric, malic and ascorbic as major organic acids in Vitis spp. root exudates. Plants reacted to Fe deficiency condition exuding a higher amount of ascorbic acid in the rhizosphere. The presence of HEPES in the medium favoured the malic acid exudation. The lowest concentration of oxalic acid was found in exudates of plants subjected to Fe-heme and could be associated to a higher accumulation in their root tips visualized by SEM analysis. PMID- 26276276 TI - Dissipation of the fungicide hexaconazole in oil palm plantation. AB - Hexaconazole is a potential fungicide to be used in the oil palm plantation for controlling the basal stem root (BSR) disease caused by Ganoderma boninense. Therefore, the dissipation rate of hexaconazole in an oil palm agroecosystem under field conditions was studied. Two experimental plots were treated with hexaconazole at the recommended dosage of 4.5 g a.i. palm(-1) (active ingredient) and at double the recommended dosage (9.0 g a.i. palm(-1)), whilst one plot was untreated as control. The residue of hexaconazole was detected in soil samples in the range of 2.74 to 0.78 and 7.13 to 1.66 mg kg(-1) at the recommended and double recommended dosage plots, respectively. An initial relatively rapid dissipation rate of hexaconazole residues occurred but reduced with time. The dissipation of hexaconazole in soil was described using first-order kinetics with the value of coefficient regression (r (2) > 0.8). The results indicated that hexaconazole has moderate persistence in the soil and the half-life was found to be 69.3 and 86.6 days in the recommended and double recommended dosage plot, respectively. The results obtained highlight that downward movement of hexaconazole was led by preferential flow as shown in image analysis. It can be concluded that varying soil conditions, environmental factors, and pesticide chemical properties of hexaconazole has a significant impact on dissipation of hexaconazole in soil under humid conditions. PMID- 26276278 TI - Using a systematic review in clinical decision making: a pilot parallel, randomized controlled trial. AB - BACKGROUND: Evidence suggests that systematic reviews are used infrequently by physicians in clinical decision-making. One proposed solution is to create filtered resources so that information is validated and refined in order to be read quickly. Two shortened systematic review formats were developed to enhance their use in clinical decision-making. METHODS: To prepare for a full-scale trial, we conducted a pilot study to test methods and procedures in order to refine the processes. A recruitment email was sent to physicians practicing full- or part-time in family medicine or general internal medicine. The pilot study took place in an online environment and eligible physicians were randomized to one of the systematic review formats (shortened or full-length) and instructed to read the document. Participants were asked to provide the clinical bottom line and apply the information presented to a clinical scenario. Participants' answers were evaluated independently by two investigators against "gold standard" answers prepared by an expert panel. RESULTS: Fifty-six clinicians completed the pilot study within a 2-month period with a response rate of 4.3 %. Agreement between investigators in assessing participants' answers was determined by calculating a kappa statistic. Two questions were assessed separately, and a kappa statistic was calculated at 1.00 (100 % agreement) for each. CONCLUSIONS: Agreement between investigators in assessing participants' answers is satisfactory. Although recruitment for the pilot study was completed in a reasonable time-frame, response rates were low and will require large numbers of contacts. The results indicate that conducting a full-scale trial is feasible. TRIAL REGISTRATION: ClinicalTrials.gov NCT02414360 . PMID- 26276279 TI - Andrographolide effect on both Plasmodium falciparum infected and non infected RBCs membranes. AB - OBJECTIVE: To explore whether its antiplasmodium effect of andrographolide is attributed to its plausible effect on the plasma membrane of both Plasmodium falciparum infected and non-infected RBCs. METHODS: Anti-plasmodium effect of andrographolide against Plasmodium falciparum strains was screened using the conventional malaria drug sensitivity assay. The drug was incubated with uninfected RBCs to monitor its effect on their morphology, integrity and osmotic fragility. It was incubated with the plasmodium infected RBCs to monitor its effect on the parasite induced permeation pathways. Its effect on the potential of merozoites to invade new RBCs was tested using merozoite invasion assay. RESULTS: It showed that at andrographolide was innocuous to RBCs at concentrations approach its therapeutic level against plasmodia. Nevertheless, this inertness was dwindled at higher concentrations. CONCLUSIONS: In spite of its success to inhibit plasmodium induced permeation pathway and the potential of merozoites to invade new RBCs, its anti-plasmodium effect can't be attributed to these functions as they were attained at concentrations higher than what is required to eradicate the parasite. Consequently, other mechanisms may be associated with its claimed actions. PMID- 26276280 TI - Immunogenicity and efficacy of recombinant 78 kDa antigen of Leishmania donovani formulated in various adjuvants against murine visceral leishmaniasis. AB - OBJECTIVE: To analyze the protective efficacy of recombinant 78 kDa antigen of Leishmania donovani in combination with two adjuvants, that is, cationic liposomes or MPL-A against visceral leishmaniasis in BALB/c mice. METHODS: The genomic DNA of promastigotes was isolated and 583 bp of T cell epitopes of gene encoding 78 kDa was amplified using specific primers. The amplified gene was cloned into pET28c, transformed into Escherichia coli BL21 (DE3) and got expressed after IPTG induction. The recombinant protein was then purified using Ni-NTA and named r78. Three groups of mice were immunized with 10 MUg of r78 plus MPL-A, r78 encapsulated in positively charged liposomes and control animals immunized with PBS. Two booster doses were given with the respective vaccine at an interval of 2 weeks each. Mice were challenged with 1 * 10(7)Leishmania promastigotes and sacrificed on different post infection/challenge days. RESULTS: Immunization with r78 along with MPL-A and liposome-encapsulated r78 brought a significant reduction in parasite load. In comparison to the infected controls, the parasite load declined by 96.2% in mice immunized with r78 plus MPL-A and 97.23% in animals immunized with liposome-encapsulated r78. The immunized animals also exhibited profound DTH response. The serum antibody responses increased from 15 to 90 days post infection/challenge. Immunized animals showed greater IgG2a levels and lesser IgG1 levels in comparison to the infected controls. The splenocytes from immunized mice were cultured, stimulated with r78 and analyzed for cytokine profile. The levels of IL-2 and IFN-gamma were greater in immunized animals as compared to control mice. CONCLUSIONS: The study proves that r78 in combination with suitable adjuvants is a potential vaccine candidate and may be instrumental in control of visceral leishmaniasis. PMID- 26276281 TI - Oral administration of Sauce lloron extract to growing lambs to control gastrointestinal nematodes and Moniezia spp. AB - OBJECTIVE: To explore anthelmintic effects of oral administration of aqueous extract of Sauce lloron (Salix babylonica; SB) against gastrointestinal nematodes and Moniezia spp. METHODS: Sixteen Pelibuey male lambs of 3-4 months of age and (23.7 +/- 3.3) kg body weight were used in a completely randomized design to be fed a total mixed ration (Control; SB0), or Control plus SB extract using 20 (SB20), 40 (SB40) and 60 (SB60) mL/lamb(/)day for 45 days. Lambs had a natural gastrointestinal nematodes and Moniezia spp. infection and had never been treated with chemical anthelmintic drugs. Individual faecal samples were collected for ova counting using McMaster procedure after 0, 7, 14, 21, 30 and 45 days post extract administration. RESULTS: No extract dose * day interactions for both gastrointestinal nematodes and Moniezia spp. egg count were found. Administration of SB extract had a higher effect (quadratic effect, P = 0.006 4) at dose of 20 mL SB/lamb/day for gastrointestinal nematode eggs during the first 21 days; however, the dose of SB40 tended (linear effect, P = 0.089 7) to be more effective than the others for Moniezia spp. egg during the first 7 days. Sampling day had a linear (P = 0.043 6) effect on Moniezia spp. egg count. CONCLUSIONS: The aqueous extract of SB could be more effective against nematodes at 20 and at 40 mL/lamb/day for Moniezia spp. The use of the SB extract could represent a promising alternative to synthetic anthelmintics for the treatment of gastrointestinal nematodes and Moniezia spp. in small ruminants from organic and conventional production systems. PMID- 26276282 TI - Hepatoprotective and proapoptotic effect of Ecballium elaterium on CCl4-induced hepatotoxicity in rats. AB - OBJECTIVES: To investigate the effects of perorally administered juice on tetrachloromethane (CCl4)-induced hepatotoxicity model in rats. METHODS: Male Wistar rats were tube-administrated silymarin, Ecballium juice at 0.2 mL/kg and 0.7 mL/kg daily for 3 consequent days, i.e., 3.28 MUg and 11.48 MUg of cucurbitacin B per kg of body weight respectively. On the third day, liver damage was induced by intraperitoneal application of CCl4. On the fourth day, abdominal cavity was macroscopically examined and liver samples were taken for histopathological and immunochemical evaluation. HPLC was used to determine the content of the active substance cucurbitacin B. RESULTS: The experiment revealed that 0.7 ml/kg juice concentration expressed the highest pro-apoptotic activity, but with prevailing negative effects. Compared with the lower concentration, there was an observable vasodilatation with consequent interstitial hemorrhages and a larger scope of inflammatory damage, which suppressed the hepatoprotective effect. In the 0.2 mL/kg concentration, there was a smaller pro-apoptotic activity but other parameters had better results, and the liver parenchyma damage was reversible. CONCLUSIONS: No reactions confirming the potentially allergic effect on laboratory rats were observed; its hepatoprotective and anti inflammatory effect was confirmed on a model of acute liver damage. PMID- 26276283 TI - Evaluation of protective effect of cactus pear seed oil (Opuntia ficus-indica L. MILL.) against alloxan-induced diabetes in mice. AB - OBJECTIVE: To evaluate the in vitro antioxidant power of cactus pear seed oil [Opuntia ficus-indica L. MILL. (CPSO)] and its protective effect against chemically induced diabetes mellitus in mice. METHODS: The in vitro antioxidant effect of CPSO was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay. The preventive effect was conducted on Swiss albino mice treated with CPSO (2 mL/kg, per os), before and after a single intraperitoneal alloxan administration (100 mg/kg). Survival rate, body weight and fasting blood glucose were measured and histopathological analysis of pancreas was performed to evaluate alloxan-induced tissue injuries. RESULTS: CPSO exhibited an antioxidant effect in DPPH scavenging assay. Moreover, the administration of CPSO (2 mL/kg) significantly attenuated alloxan-induced death and hyperglycemia (P < 0.001) in treated mice. Morphometric study of pancreas revealed that CPSO significantly protected islets of langerhans against alloxan induced-tissue alterations. CONCLUSIONS: Based on theses results, CPSO can prevente alloxan-induced-diabetes by quenching free radicals produced by alloxan and inhibiting tissue injuries in pancreatic beta-cells. PMID- 26276284 TI - Antimicrobial activity and synergism of Sami-Hyanglyun-Hwan with ciprofloxacin against methicillin-resistant Staphylococcus aureus. AB - OBJECTIVE: To investigate the antibacterial activity of SHH extracted with either water or ethanol against methicillin-resistant Staphylococcus aureus (MRSA) and combinatory antimicrobial effect with ciprofloxacin (CIP) by time kill assay and checkerboard dilution test. METHODS: The antibacterial activity determined by broth dilution method indicated that the antibacterial activity of Sami-Hyanglyun Hwan (SHH) water extract (SHHW) and SHH ethanol extract (SHHE) ranged from 250 to 2000 MUg/mL and 125 to 1000 MUg/mL against MRSA, respectively. RESULTS: In the checkerboard method, the combinations of SHHE with CIP had a partial synergistic or synergistic effect against MRSA. The time-kill curves showed that a combined SHHE and CIP treatment reduced the bacterial counts dramatically after 24 h. CONCLUSIONS: The present study demonstrates the therapeutic ability of SHHE against MRSA infections. PMID- 26276285 TI - Role of Aedes aegypti and Aedes albopictus during the 2011 dengue fever epidemics in Hanoi, Vietnam. AB - OBJECTIVE: To record the human cases of dengue fever (DF) and investigate the Aedes mosquito species circulating during the Hanoi 2011 DF epidemics. METHODS: 24 different outbreak points were recorded in 8 districts between August and December 2011. RESULTS: 140 patients were hospitalized following dengue diagnostic with a predominance of males (59.3%) and the 15-34 age class. Only DENV-1 (11.27%) and DENV-2 (88.73%) serotypes were detected in human samples. Mosquito sampling performed in and around patients households revealed the predominance of Aedes aegypti (A. aegypti) (95.15%) versus Aedes albopictus (4.85%). CONCLUSIONS: There is a positive correlation between the population density of A. aegypti and the number of human cases and duration of outbreaks. This was not observed for Aedes albopictus. Three pools of A. aegypti were positive with dengue virus, two with DENV-1 and one with DENV-2. PMID- 26276286 TI - Sero-prevalence and associated risk factors of Toxoplasma gondii infection among pregnant women attending antenatal care at Felege Hiwot Referral Hospital, northwest Ethiopia. AB - OBJECTIVE: To determine the prevalence of toxoplasmosis and to assess the possible risk factors associated with the infection among pregnant women attending antenatal care center at Felege Hiwot Referral Hospital, Bahir Dar town, northwest Ethiopia. METHODS: A hospital based cross-sectional study was designed to determine the prevalence of toxoplasmosis among pregnant women. Three hundred eighty four serum samples were collected from November 2013 to January 2014. Data on socio-demographic and predisposing factors were collected from each study participant with simple random sampling technique. The serum samples were examined for anti-Toxoplasma gondii (T. gondii) antibodies using latex agglutination test. RESULTS: The overall seroprevalence of T. gondii among the pregnant women was 18.5%. All of T. gondii positive cases found to be positive only for IgG antibody. Significant association was observed between seroprevalence and presence of domestic cats [AOR = 2.85, 95% CI: 1.66-4.90, P = 0.000], consumption of raw or undercooked meat [AOR = 1.98, 95% CI: 1.15-2.43, P = 0.014] and history of abortion [AOR = 2.47, 95% CI: 1.40-4.34, P = 0.002]. No significant association was observed between seroprevalence and socio-demographic characters, gestational age, gravidity, consumption of raw vegetable, and blood transfusion. CONCLUSIONS: The seroprevalence of toxoplasmosis among pregnant women in Bahir Dar town was relatively high. Presence of domestic cats at home and consumption of raw or undercooked meat were identified as main risk factors for T. gondii infection. Therefore, health education towards avoiding eating raw or undercooked meat and avoiding contact with cats are recommended for prevention of miscarriage or defects during pregnancy. PMID- 26276287 TI - Effect of PDGF-Rb antagonist imatinib on endometrial injury repairing in mouse model. AB - OBJECTIVE: To study the effects of PDGF-Rb antagonists imatinib on endometrial injury repairing in the mouse model. METHODS: The cultured MSCs cells from male mice were marked with BrdU in vitro, and then transplanted to the female mice which suffered from radiation injury through tail vein, PDGF-Rb antagonists imatinib was injected through abdominal cavity. Four groups were arranged, which were radiation transplantation group, normal control group, imatinib intervention group and radiation control group. BrdU incorporation, SRY expression and MVD status were detected in uterus of mice. RESULTS: SRY gene was negative expressed in normal control group and radiation control group. SRY gene presented positive in radiation transplantation group and imatinib intervention group; BrdU incorporation showed negative in radiation control group and normal control group which died in the early stage in mice; the incorporation of BrdU was higher in radiation transplantation group compared with imatinib intervention group; CD34 was positive on the uterus of all the four groups, which showed highest in radiation control group and lowest in radiation control group; The MVD in imatinib intervention group was lower than radiation control group; the difference of MVD was significantly compared with normal control group (P < 0.05). CONCLUSIONS: PDGF-Rb antagonists imatinib could inhibit the repairing function of MSCs in the endometrial lesions in mice. PMID- 26276288 TI - Anti-tumor effect of LTA combined with 5-FU on H22 tumor bearing mice. AB - OBJECTIVE: To study the effect of lipoteichoic acid (LTA) and 5-FU on the expression of caspase-3, EGFR, TGF-alpha proteins of tumor tissue of H22 cancer bearing mice and its anti-tumor mechanism. METHODS: A total of 40 SPF grade Kunming mice were selected to establish H22 liver cancer model, and then the mice were divided into 4 groups at random with ten mice in each group. Group A was given saline lavage treatment, Group B was treated with 5-FU by intraperitoneal injection, Group C was treated with LTA by lump body injection; Group D was treated with LTA by lump body injection and 5-FU by intraperitoneal injection. Two weeks after the treatment, the mice in each group were executed and the tumor tissue was stripping and weighted, and the tumor growth inhibition ratio was calculated. Then the tumor tissue was processed for conventional embedding, sectioned to observe the expression of caspase-3, EGFR, TGF-alpha by immunohistochemical staining method. RESULTS: The tumor inhibitory rate o f Group D was significantly higher than Groups B and C (P < 0.05); B, the tumor inhibitory rate o f Group B had no statistical difference compared with Group C (P > 0.05). The IDO values of TGF-alpha, EGFR proteins in Groups B, C, D mice tumor tissue were significantly lower than that in group A (P < 0.05); while IDO value of caspase-3 in Groups B, C, D group mice tumor tissue was significantly higher than that in Group A (P < 0.05). The IDO value of TGF-alpha, EGFR in Group D mice tumor tissue were significantly lower than that in Groups B and C; While IDO value of aspase-3 in Group D was significantly higher than that in Groups B and C (P < 0.05). CONCLUSIONS: LTA combined with 5-FU can effectively inhibit the tumorigenesis of H22 tumor bearing mice, increase the caspase-3 protein expression, inhibit TGF-alpha and EGFR protein expression, further promote tumor cell apoptosis and play a synergistic antitumor effect. PMID- 26276289 TI - Effect of subarachnoid nerve block anesthesia on glutamate transporter GLAST and GLT-1 expressions in rabbits. AB - OBJECTIVE: To observe the effect of subarachnoid nerve block anesthesia on glutamate transporter glutamate-aspartate transporter (GLAST) and GLT-1 expressions in rabbits, and to investigate the effect of peripheral nerve anesthesia on the morphology and function of the spinal cord. METHODS: Twenty healthy New Zealand white rabbits were randomly divided into two groups: the experimental group and control group; with 10 rabbits in each group. For spinal nerve anesthesia, 5 g/L of bupivacaine was used in the experimental group, and sterile saline was used in the control group. After 30 min of cardiac perfusion, GLAST and GLT-1 protein expression in spinal neurons were detected by immunohistochemistry and immunofluorescence staining. RESULTS: GLAST and GLT-1 protein-positive cells increased in neurons in the experimental group, compared with the control group (P < 0.05). CONCLUSIONS: After subarachnoid nerve block anesthesia, rabbit glutamate transporter GLAST and GLT-1 expression is increased; and spinal cord nerve cell function is inhibited. PMID- 26276290 TI - Relationship between gene polymorphisms and prostate cancer risk. AB - OBJECTIVE: To investigate the relationship between genetic factor and prostate cancer (Pca) risk and the possible cause in it. METHODS: The polymorphisms of cytochrome P450 family 17 (CYPl7) rs743572, p27 V109G and androgen receptor (AR) gene CAG repeat length in peripheral blood from 70 cases and 70 controls were detected through the polymerase chain reaction-restriction fragment length polymorphism technique or short tandem repeat-polymerase chain reaction technique. Then, according to the results of case-control study, the recombinant plasmids containing the wild/mutant p27 gene were constructed and transfected Pca LNcap cells. After 24 and 72 h of transfection, the cell proliferative activity was determined by MTT method, cell cycle distribution and apoptosis was detected by flow cytometry, and the expression level of bcl-2, caspase-3 and p27 protein was determined by Western-blot. RESULTS: In three target polymorphisms, only p27 V109G polymorphism was related to Pca risk (P = 0.030, OR = 0.202, 95% CI = 0.042 0.973). Pca risk of p27-109G allele was lower than -109V allele (P = 0.006, OR = 0.285, 95% CI = 0.110-0.737). Cells transfected with wild/mutant p27 gene both showed the higher cells apoptosis rate and the lower cell proliferative activity than mock cells (P < 0.05 or 0.01), the regulatory effect of mutant p27 on cell proliferation and apoptosis was stronger than the wild p27 (P < 0.05). CONCLUSIONS: p27-109G allele that could cause higher p27 protein expression than 109V allele in LNcap cells, maybe is the protective factor of Pca. PMID- 26276291 TI - Expression of transferrin in hematoma brain tissue at different stages after intra cerebral hemorrhage in rats. AB - OBJECTIVE: To explore the expression of transferrin (Tf) and transferrin receptor (TfR) in hematoma brain tissue at different stage after intracerebral hemorrhage (ICH) in rats. METHODS: ICH rats model were established by collagenase method, and rats were sacrificed at 24 h, 72 h, 7 d and 14 d after operation. The levels of Tf and TfR in different periods of rats were detected by immunohistochemical method, and correlation between two groups was analyzed. RESULTS: Tf, TfR positive cells at each time after operation in observation group were significantly higher than that in control group (P < 0.05). Tf, TfR-positive cells began to increase from 24 h after the operation and reached the peak 72 h-7 d after surgery, but then gradually decreased. Tf was mainly expressed in nucleus and cytoplasm of neurons and glial cells around the hematoma, but TfR was mainly expressed in nucleus and cytoplasm of neurons and choroid plexus endothelial cells. Correlation analysis showed that the Tf-positive cell was significantly positively correlated with TfR-positive cell expression (r = 0.447, P = 0.022). CONCLUSIONS: Tf and TfR were important transporters in brain tissue excessive load iron transport after ICH, and detecting the expression levels of the two indicators can provide a reference for prognosis treatment in ICH. PMID- 26276292 TI - Effect of salinomycin on metastasis and invasion of bladder cancer cell line T24. AB - OBJECTIVE: To explore the effect of salinomycin on the metastasis and invasion of bladder cancer cell line T24 by regulating the related protein expression in the process of epithelial-mesenchymal transition (EMT), and to provide experimental basis for the treatment of urological tumors. METHODS: The bladder cancer cell line T24 was cultured in vitro. The rat bladder tumor model was established in vivo. The rats were randomized into two groups, among which the rats in the experiment group were given intraperitoneal injection of salinomycin, while the rats in the control group were given intraperitoneal injection of normal saline. The change of tumor cells in the two groups was observed. Transwell was used to detect the cell migration and invasion abilities, Real-time PCR was used to detect the expression of mRNA, while Western-blot was utilized for the determination of the expressions of E-cadherin and vimentin proteins. RESULTS: The metastasis and invasion abilities of serum bladder cancer cell line T24 after salinomycin treatment in the experiment group were significantly reduced when compared with those in the control group, and the tumor metastasis lesions were decreased from an average of 1.59 to 0.6 (P < 0.05). T24 cell proliferation in the experiment group was gradually decreasing. T24 cell proliferation at 48 h was significantly lower than that at 12 h and 24 h (P < 0.05). T24 cell proliferation at 24 h was significantly lower than that at 12 h (P < 0.05). T24 cell proliferation at each timing point in the experiment group was significantly lower than that in the control group (P < 0.05). The serum mRNA level and E cadherin expression in the tumor tissues in the experiment group were significantly higher than those in the control group, while vimentin expression level was significantly lower than that in the control group (P < 0.05). CONCLUSIONS: Salinomycin can suppress the metastasis and invasion of bladder cancer cells, of which the mechanism is probably associated with the inhibition of EMT of tumor cells. PMID- 26276294 TI - Risk factors of polycystic ovarian syndrome among Li People. AB - OBJECTIVE: To study the relevant risk factors of polycystic ovarian syndrome (PCOS) of Li People so as to provide basis for early diagnosis and treatment of PCOS. METHODS: With case-control study method, 285 cases of PCOS of Li People were as recruited case group, and 580 cases of non-PCOS of female Li People as control group. Questionnaire was adopted to collect data regarding risk factors of PCOS, then the risk factors of PCOS was searched by univariate and multivariate analysis. RESULTS: Multivariate analysis showed that the risk factors of PCOS included in menstrual cycle disorder (OR = 5.824), bad mood (OR = 2.852), family history of diabetes (OR = 7.008), family history of infertility (OR = 11.953), menstrual irregularity of mother (OR = 2.557) and lack of physical exercise (OR = 1.866). CONCLUSIONS: To target the high risk factors of menstrual cycle disorder, family history of diabetes, family history of infertility, family history of diabetes, bad mood and lack of physical exercise of female population, we should implement early screen, diagnose and treatment of POCS in order to reduce the incidence rate of PCOS and improve prognosis of PCOS. PMID- 26276293 TI - Influence of overexpression of SOCS2 on cells of DN rat. AB - OBJECTIVE: To explore the influence and mechanism of overexpression of SOCS2 on diabetic nephropathy (DN) rats and cells. METHODS: STZ was used to induce male SD rats and SOCS2 was injected into left renal vein. Rats were divided into DN group, DN-Ad-null group and DN-Ad-SOCS2 group. Glucose with high and normal concentration was used to culture HBZY-1 cells and then transfect Ad-SOCS2. HG group, HG-Ad-null group, HG-Ad-SOCS2 group, CG group, CG-Ad-null group, and CG-Ad SOCS2 group were created. The expression of inflammatory cytokines (MCP-1, TNF alpha and IL-6) in kidney tissue of rats, fibrosis related protein (FN, Collagen IV and TGF-beta) in kidney tissue and cells of rats, and JAK/STAT signaling pathway related proteins (p-JAK2 and p-STAT3) were tested by western blot. ELISA was used to test the expression of inflammatory cytokines (TNF-alpha and IL-6) in cells. RESULTS: The expression of inflammatory cytokines in DN rats (MCP-1, TNF alpha and IL-6) and cell (TNF-alpha and IL-6) were increased (P < 0.01) significantly. However, SOCS2 could decrease the overexpression of mediated inflammatory cytokines in DN animal models and cell models (P < 0.01). The expression of fibrosis related protein in DN rats and cells increased while SOCS2 decreased the overexpression of mediated fibrosis related protein in DN model rats and cells (P < 0.01). The expression of JAK/STAT pathway related protein in both DN rats and cells increased and the JAK/STAT signaling pathway was activated. Yet, SOCS2 obviously suppressed the expression of the JAK/STAT signaling pathway as well as the related proteins (p-JAK2 and p-STAT3) in both DN rats and cells. CONCLUSIONS: The overexpression of SOCS2 can decrease the expression of inflammatory cytokines and fibrosis related proteins in DN rats and cells, and meanwhile suppress the activation of JAK/STAT signaling pathway mediated by DN. PMID- 26276295 TI - [News in sport's cardiology: too much sport harmful for the heart?]. AB - Essentials moderate and regular physical activity is beneficial at any age and whatever medical and surgical history. His practice must always be encouraged. The practice of a sport competition has no additional health benefit. The signs of athlete's heart may exit standards, we must know them to prevent against abusive indications. In some typically male subjects a priori predisposed veterans and often a sport, especially too intensive endurance can be harmful to the cardiovascular system. Orthostatic intolerance and atrial fibrillation are the most frequent, the decrease of sport is justified. Current scientific evidence is not sufficiently substantiated to routinely advising against an intense sport endurance. However, after 60years it should prevent the sporting potential risks of too intensive sports practice and discourage him practice with a competitive spirit. PMID- 26276296 TI - [Do weather and seasons influence our heart?]. AB - There are numerous publications about impact of meteo, seasons and pollution on cardiovascular diseases. Cardiovascular diseases, in particular myocardial infarction and heart failure, have been consistently more frequent during winter in the northern and southern hemisphere. Chronic exposure to air pollution influences the development of atherosclerosis and increases the risk for coronary artery disease. There is a positive association between short-term increase in gaseous components with the risk of hospitalization or death from congestive heart failure. The considerable impact on health care service warrants a comprehensive approach to cardiovascular disease management. PMID- 26276297 TI - [Optimal duration of anticoagulant treatment after venous thromboembolic disease]. AB - Determination of the optimal duration of anticoagulant treatment for venous thromboembolic disease (VTED) is a major step in the management of patients with this disease. The assessment depends on the identification of two sets of risk factors: those for recurrence after anticoagulant treatment is stopped and those for hemorrhage in cases of prolonged treatment. Nonetheless, the determination of the optimal duration remains controversial. Recent data finally make it possible to clarify this decision. Recent treatment trials demonstrate that patients at high risk of recurrence receive no sustained benefit from a prolonged but limited anticoagulant treatment. In other words, the choice is simplified: either the risk is low, and treatment for 3months is sufficient, or the risk is high, and treatment must be envisioned for an unlimited duration. Adequate identification of patients eligible for short or unlimited treatment is more crucial than ever and depends on the presence of determinant clinical variables, as the information from laboratory or morphologic tests is generally marginal. The risk of thromboembolic recurrence is low when the initial episode is triggered by a major reversible factor, and a short treatment of 3months is thus indicated. These inducing factors are mainly surgery, lower limb injuries, immobilization for a medical condition, pregnancy, or use of combined estrogen-progestin contraceptives. Among patients with VTED not induced by these factors, the risk of recurrence is high and requires planning anticoagulant treatment for an unlimited duration. Nonetheless, the risk of hemorrhage is a major constraint to such unlimited treatment. Accordingly, the perspectives for secondary prevention that is equally effective but has a lower risk of hemorrhage are currently under evaluation. Finally, patients with cancer are in a separate category, with a very high risk of recurrence that justifies treatment for at least 6months. PMID- 26276298 TI - Metallic mercury use by South African traditional health practitioners: perceptions and practices. AB - BACKGROUND: Mercury is a toxic metal however its use in traditional healthcare systems remains widespread. The aim of this study was to determine the prevalence of mercury use by South African Traditional Health Practitioners (THP) and to document reasons for use and administration methods. METHODS: A cross-sectional study design was employed. A total of 201 THPs were enrolled from two main metropolitan areas of KwaZulu-Natal (South Africa), and 198 were included in the final analysis. Information on demographic characteristics, reasons for using or not using mercury as well as mercury administration methods were collected. RESULTS: Of the 198 THPs, 78 (39%) used mercury for healing purposes and 74 (95%) of the mercury users stated that they were taught to use it by another THP. The two main routes of administration were oral and sub-cutaneous implantations (ukugcaba) at 85% (n = 66) and 59% (n = 46), respectively. The most common responses for mercury administration were for child birth (n = 70; 90%) and protection against guns (n = 39; 50%). CONCLUSION: This is the first study to describe the prevalence and practice of mercury use in South African traditional medicine. Socio-cultural mercury use is a potential source of exposure to both THPs and their patients. In light of such findings, public education messages and regulatory measures need to be effected. PMID- 26276299 TI - Mapping system for portal placement in laparoscopic procedures of small animals. AB - BACKGROUND: Current recommendations for portal placement in laparoscopy are often imprecise. The aim of this study was to establish and evaluate a mapping system for portal placement during laparoscopic procedures in small animals. Sixty-four final-year veterinary students took part in this in papyro study. Descriptions of portal placements of two recent veterinary laparoscopic papers were randomly chosen as templates. The students performed portal placement based either on the description in the papers or based on the orthogonal mapping system for portal placement developed by the authors in a previous pilot study. The participants were randomly divided into two groups and asked to virtually chart positions of the portals on two photographs of a dog's abdomen. Group A (n = 31) placed the portals using the mapping system, and Group B (n = 33) placed the portals based on the explanations provided in two randomly selected studies. RESULTS: Group A achieved an overall correct placement rate of 94.91 % (87.1-100.0 %) with an overall mean distance of 1.31 mm (0.00-3.61 mm) from the desired placement points. Group B achieved an overall correct placement rate of 40.8 % (3.1-93.3 %) with an overall mean distance of 16.97 mm (7.17-27.63 mm) from the desired placement points. The students in Group A performed significantly better than did students in Group B (P < .05). CONCLUSIONS: Use of the mapping system significantly improved correct portal placement in a dog photograph model. Use of such systems in laparoscopy may help facilitate correct portal placement and improve the repeatability of procedures, especially for the novice surgeon. PMID- 26276300 TI - The Glass Houses of Attending Surgeons: An Assessment of Unprofessional Behavior on Facebook Among Practicing Surgeons. AB - PURPOSE: Our recent publication demonstrated that unprofessional behavior on Facebook is common among surgical residents. In the formulation of standards and curricula to address this issue, it is important that surgical faculty lead by example. Our current study refocuses on the Facebook profiles of faculty surgeons involved in the education of general surgery residents. METHODS: The American College of Surgeons (ACS) web site was used to identify general surgery residencies located in the Midwest. Departmental web sites were then searched to identify teaching faculty for the general surgery residency. Facebook was then searched to determine which faculty had profiles available for viewing by the general public. Profiles were then placed in 1 of the 3 following categories: professional, potentially unprofessional, or clearly unprofessional. STATISTICAL ANALYSIS: A chi-square test was used to determine significance. RESULTS: In all, 57 residency programs were identified on the ACS web site, 100% of which provided an institutional web site listing the surgical faculty. A total of 758 general surgery faculty were identified (133 women and 625 men), of which 195 (25.7%) had identifiable Facebook accounts. In all, 165 faculty (84.6%) had no unprofessional content, 20 (10.3%) had potentially unprofessional content, and 10 (5.1%) had clearly unprofessional content. Inter-rater reliability was good (88.9% agreement, kappa = 0.784). Clearly unprofessional behavior was found only in male surgeons. For male surgeons, clearly unprofessional behavior was more common among those in practice for less than 5 years (p = 0.031). Alcohol and politics were the most commonly found variables in the potentially unprofessional group. Inappropriate language and sexually suggestive material were the most commonly found variables in the clearly unprofessional group. CONCLUSIONS: Unprofessional behavior on Facebook is less common among surgical faculty compared with surgical residents. However, the rates remain unacceptably high, especially among men and those in practice for less than 5 years. Education on the dangers of social media should not be limited to residents but should instead be extended to attending surgeons as well. PMID- 26276301 TI - Development of a PROficiency-Based StePwise Endovascular Curricular Training (PROSPECT) Program. AB - OBJECTIVES: Focus on patient safety, work-hour limitations, and cost-effective education is putting pressure to improve curricula to acquire minimally invasive techniques during surgical training. This study aimed to design a structured training program for endovascular skills and validate its assessment methods. DESIGN: A PROficiency-based StePwise Endovascular Curricular Training (PROSPECT) program was developed, consisting of e-learning and hands-on simulation modules, focusing on iliac and superficial femoral artery atherosclerotic disease. Construct validity was investigated. Performances were assessed using multiple choice questionnaires, valid simulation parameters, global rating scorings, and examiner checklists. Feasibility was assessed by passage of 2 final-year medical students through this PROSPECT program. SETTING: Ghent University Hospital, a tertiary clinical care and academic center in Belgium with general surgery residency program. PARTICIPANTS: Senior-year medical students were recruited at Ghent University Hospital. Vascular surgeons were invited to participate during conferences and meetings if they had performed at least 100 endovascular procedures as the primary operator during the last 2 years. RESULTS: Overall, 29 medical students and 20 vascular surgeons participated. Vascular surgeons obtained higher multiple-choice questionnaire scores (median: 24.5-22.0 vs. 15.0 12.0; p < 0.001). Students took significantly longer to treat any iliac or femoral artery stenosis (3.3-14.8 vs. 5.8-30.1min; p = 0.001-0.04), whereas in more complex cases, fluoroscopy time was significantly higher in students (8.3 vs. 21.3min; p = 0.002; 7.3 vs. 13.1min; p = 0.03). In all cases, vascular surgeons scored higher on global rating scorings (51.0-42.0 vs. 29.5-18.0; p < 0.001) and examiner checklist (81.5-75.0 vs. 54.5-43.0; p < 0.001). Hence, proficiency levels based on median expert scores could be determined. There were 2 students who completed the program and passed for each step within a 3-month period during their internships. CONCLUSIONS: A feasible and construct validated surgical program to train cognitive, technical, and nontechnical endovascular skills was developed. A structured, stepwise, proficiency-based valid endovascular program to train cognitive, technical, and human factor skills has been developed and proven to be feasible. A randomized controlled trial has been initiated to investigate its effect on performances in real life, patient outcomes, and cost-effectiveness. PMID- 26276302 TI - Graduating Students' and Surgery Program Directors' Views of the Association of American Medical Colleges Core Entrustable Professional Activities for Entering Residency: Where are the Gaps? AB - OBJECTIVE: Residency program directors have increasingly expressed concern about the preparedness of some medical school graduates for residency training. The Association of American Medical Colleges recently defined 13 core entrustable professional activities (EPAs) for entering residency that residents should be able to perform without direct supervision on the first day of training. It is not known how students' perception of their competency with these activities compares with that of surgery program directors'. DESIGN: Cross-sectional survey. SETTING: All surgery training programs in the United States. PARTICIPANTS: All program directors (PDs) in the Association of Program Directors in Surgery (APDS) database (n = 222) were invited to participate in an electronic survey, and 119 complete responses were received (53.6%). Among the respondents, 83% were men and 35.2% represented community hospital programs. PDs' responses were compared with questions asking students to rate their confidence in performance of each EPA from the Association of American Medical Colleges Graduation Questionnaire (95% response). RESULTS: PDs rated their confidence in residents' performance without direct supervision for every EPA significantly lower when compared with the rating by graduating students. Although PDs' ratings continued to be lower than students' ratings, PDs from academic programs (those associated with a medical school) gave higher ratings than those from community programs. PDs generally ranked all 13 EPAs as important to being a trustworthy physician. PDs from programs without preliminary residents gave higher ratings for confidence with EPA performance as compared with PDs with preliminary residents. Among PDs with preliminary residents, there were equal numbers of those who agreed and those who disagreed that there are no identifiable differences between categorical and preliminary residents (42.7% and 41.8%, respectively). CONCLUSIONS: A large gap exists between confidence in performance of the 13 core EPAs for entering residency without direct supervision for graduating medical students and surgery program directors. Both the groups identified several key areas for improvement that may be addressed by medical school curricular interventions or expanding surgical boot camps in hopes to improve resident performance and patient safety. PMID- 26276303 TI - Wearable Technology for Global Surgical Teleproctoring. AB - OBJECTIVE: In underserved communities around the world, inguinal hernias represent a significant burden of surgically-treatable disease. With traditional models of international surgical assistance limited to mission trips, a standardized framework to strengthen local healthcare systems is lacking. We established a surgical education model using web-based tools and wearable technology to allow for long-term proctoring and assessment in a resource-poor setting. This is a feasibility study examining wearable technology and web-based performance rating tools for long-term proctoring in an international setting. METHODS: Using the Lichtenstein inguinal hernia repair as the index surgical procedure, local surgeons in Paraguay and Brazil were trained in person by visiting international expert trainers using a formal, standardized teaching protocol. Surgeries were captured in real-time using Google Glass and transmitted wirelessly to an online video stream, permitting real-time observation and proctoring by mentoring surgeon experts in remote locations around the world. A system for ongoing remote evaluation and support by experienced surgeons was established using the Lichtenstein-specific Operative Performance Rating Scale. RESULTS: Data were collected from 4 sequential training operations for surgeons trained in both Paraguay and Brazil. With continuous internet connectivity, live streaming of the surgeries was successful. The Operative Performance Rating Scale was immediately used after each operation. Both surgeons demonstrated proficiency at the completion of the fourth case. CONCLUSIONS: A sustainable model for surgical training and proctoring to empower local surgeons in resource-poor locations and "train trainers" is feasible with wearable technology and web-based communication. Capacity building by maximizing use of local resources and expertise offers a long-term solution to reducing the global burden of surgically treatable disease. PMID- 26276304 TI - Innovation in Pediatric Surgical Education for General Surgery Residents: A Mobile Web Resource. AB - BACKGROUND/OBJECTIVES: General surgery residents lack a standardized educational experience in pediatric surgery. We hypothesized that the development of a mobile educational interface would provide general surgery residents broader access to pediatric surgical education materials. METHODS: We created an educational mobile website for general surgery residents rotating on pediatric surgery, which included a curriculum, multimedia resources, the Operative Performance Rating Scale (OPRS), and Twitter functionality. Residents were instructed to consult the curriculum. Residents and faculty posted media using the Twitter hashtag, #UCLAPedSurg, and following each surgical procedure reviewed performance via the OPRS. Site visits, Twitter posts, and OPRS submissions were quantified from September 2013 to July 2014. RESULTS: The pediatric surgery mobile website received 257 hits; 108 to the homepage, 107 to multimedia, 28 to the syllabus, and 19 to the OPRS. All eligible residents accessed the content. The Twitter hashtag, #UCLAPedSurg, was assigned to 20 posts; the overall audience reach was 85 individuals. Participants in the mobile OPRS included 11 general surgery residents and 4 pediatric surgery faculty. CONCLUSION: Pediatric surgical education resources and operative performance evaluations are effectively administered to general surgery residents via a structured mobile platform. PMID- 26276305 TI - Glasgow Antipsychotic Side-effects Scale for Clozapine - Development and validation of a clozapine-specific side-effects scale. AB - OBJECTIVE: The authors developed and validated a clozapine-specific side-effects scale capable of eliciting the subjectively unpleasant side-effects of clozapine. METHODS: Questions from the original Glasgow Antipsychotic Side-effects Scale (GASS) were compared to a list of the most commonly reported clozapine side effects and those with a significant subjective burden were included in the GASS for Clozapine (GASS-C). The original authors of the GASS and a group of mental health professionals from the UK and Ireland were enlisted to comment on the questions in the GASS-C based on their clinical experience. 110 clozapine outpatients from two sites completed the GASS-C, the original GASS and a repeat GASS-C. Statistical analyses were performed using SPSS for Windows version 19. RESULTS: The GASS-C was shown to have construct validity, in that Spearman's correlation coefficient was 0.816 (p<0.001) with the original GASS, whilst Cohen's kappa coefficient was >0.77 (p<0.001) for one question and >0.81 (p<0.001) for remaining relevant questions. GASS-C was also shown to have strong test-retest reliability, in that Cronbach's alpha coefficient was >0.907 (p<0.001), whilst Cohen's kappa coefficient was >0.81 (p<0.001) for 12 questions and >0.61 (p<0.001) for the remaining four questions. CONCLUSION: The GASS-C is a valid and reliable clinical tool to enable a systematic assessment of the subjectively unpleasant side-effects of clozapine. Future research should focus on how the scale can be utilised as a clinical tool to improve real-world outcomes such as adherence to clozapine therapy and quality of life. PMID- 26276306 TI - Social defeat predicts paranoid appraisals in people at high risk for psychosis. AB - BACKGROUND: The experience of social defeat may increase the risk of developing psychotic symptoms and psychotic disorders. We studied the relationship between social defeat and paranoid appraisal in people at high risk for psychosis in an experimental social environment created using Virtual Reality (VR). METHOD: We recruited UHR (N=64) participants and healthy volunteers (N=43). Regression analysis was used to investigate which baseline measures predicted paranoid appraisals during the VR experience. RESULTS: At baseline, UHR subjects reported significantly higher levels of social defeat than controls (OR=.957, (CI) .941 .973, p<.000). Following exposure to the VR social environment, the UHR group reported significantly more paranoid appraisals than the controls (p<.000). Within the UHR sample, paranoid appraisals were predicted by the level of social defeat at baseline, as well as by the severity of positive psychotic and disorganised symptoms. CONCLUSION: In people who are at high risk of psychosis, a history of social defeat is associated with an increased likelihood of making paranoid appraisals of social interactions. This is consistent with the notion that social defeat increases the risk of developing psychosis. PMID- 26276307 TI - Meta-analysis of data from the Psychiatric Genomics Consortium and additional samples supports association of CACNA1C with risk for schizophrenia. AB - Recently, numerous genome-wide association studies (GWASs) have identified numerous risk loci for schizophrenia, but follow-up studies are still essential to confirm those results. Therefore, we followed up on top GWAS hits by genotyping implicated loci in additional schizophrenia family samples from our own collection. Five-hundred thirty-six Asian families (comprising 1633 members including 698 schizophrenics) were genotyped in this study. We analyzed 12 single nucleotide polymorphisms (SNPs) in strongly implicated candidate genes revealed by GWASs and their follow-up studies. We then used meta-analysis to combine our results with those of the Schizophrenia Working Group of the Psychiatric Genomics Consortium (PGC). In our newly genotyped samples, there were no significant associations of any of the 12 candidate SNPs with schizophrenia; however, all genome-wide significant results from the schizophrenia PGC analysis were maintained after combination with our new data by meta-analysis. One SNP (rs4765905 in CACNA1C) showed a stronger effect and decreased p-value (5.14e-17) after meta-analysis relative to the original PGC results, with no significant between-study heterogeneity. The findings of this study support the significant results in the PGC, especially for CACNA1C. The sample size in our study was considerably smaller than that in the PGC-SCZ study; thus, the weights carried by our samples in the meta-analysis were small. Therefore, our data could not vastly reduce PGC association signals. However, we considered that the well replicated results from the PGC hold up in our new samples, and may suggest that the top hits from the PGC are generalizable, even to other ancestral groups. PMID- 26276308 TI - Outcomes of lung cancer resection for patients with combined pulmonary fibrosis and emphysema. AB - PURPOSE: Combined pulmonary fibrosis and emphysema (CPFE) has recently been reported as a prognostic factor that may increase the risk of lung cancer for patients with respiratory disorders; however, there have been no reports published on mortality and morbidity following major lung resection for patients with CPFE. METHODS: The subjects of this retrospective study were 1507 patients who underwent surgical resection of lung cancer at our institute between 2008 and 2013. We reviewed the computed tomography findings and divided the patients into four groups: CPFE group, fibrosis group, emphysema group, and normal group. The surgical outcomes of the patients with CPFE were compared with those of the patients in the other groups. RESULTS: The CPFE group comprised 137 (10.0 %) patients. This group had worse surgical morbidity and mortality rates than either the fibrosis group or the emphysema group. The 90-day mortality rates for the CPFE, fibrosis, and emphysema groups were 7.3, 0, and 3.0 %, respectively. A multivariate analysis of the CPFE group revealed that the distribution of IIP (HR 13.29, p = 0.038) and blood loss (ml) (HR 1.001, p = 0.013) predicted the hazard ratio for 90-day mortality. CONCLUSIONS: The postoperative outcome of patients with CPFE in this study was poor with respect to morbidity and mortality. The high rate of complications and poor survival warrants further investigation of the indications for surgery in patients with CPFE. PMID- 26276309 TI - Reduction of oxidative stress by an ethanolic extract of leaves of Piper betle (Paan) Linn. decreased methotrexate-induced toxicity. AB - Methotrexate (MTX), a folate antagonist, is currently used as first line therapy for autoimmune diseases like rheumatoid arthritis and psoriasis, but its use is limited by the associated hepatotoxicity. As leaves of Piper betle, belonging to family Piperaceae, have antioxidant and anti-inflammatory properties, the present study was undertaken to investigate the potential of Piper betle leaf extract (PB) in attenuating MTX-induced hepatotoxicity. Rats pre-treated with PB (50 or 100 mg kg(-1) b.w., p.o.) were administered with a single dose of MTX (20 mg kg( 1), b.w., i.p.) and its hepatoprotective efficacy was compared with folic acid (1 mg kg(-1) b.w., i.p.), conventionally used to minimize MTX-induced toxicity. MTX induced hepatotoxicity was confirmed by increased activities of marker enzymes, alanine transaminase, aspartate transaminase, and alkaline phosphatase which were remitted by pre-treatment with PB and corroborated with histopathology. Additionally, MTX-induced hepatic oxidative stress which included increased generation of reactive oxygen species, enhanced lipid peroxidation, depleted levels of glutathione and decreased activities of antioxidant enzymes was effectively mitigated by PB, indicative that its promising antioxidant-mediated hepatoprotective activity was worthy of future pharmacological consideration. PMID- 26276310 TI - NF45 overexpression is associated with poor prognosis and enhanced cell proliferation of pancreatic ductal adenocarcinoma. AB - NF45, also referred to as nuclear factor of activated T cells, has been reported to promote the progression of multiple cancer types. However, the expression and physiological significance of NF45 in pancreatic ductal adenocarcinoma (PDAC) remain largely elusive. In this study, we investigated the clinical relevance and potential role of NF45 expression in PDAC development. Western blot analysis revealed that NF45 was remarkably upregulated in PDAC tissues, compared with the adjacent non-tumorous ones. In addition, the expression of NF45 in 122 patients with PDAC was evaluated using immunohistochemistry. In this way, we found that NF45 was abundantly expressed in PDAC tissues, and the expression of NF45 was correlated with tumor size (p = 0.007), histological differentiation (p = 0.033), and TNM stage (p = 0.001). Importantly, patients with low levels of NF45 expression exhibited better postoperative prognosis as compared with those with high NF45 expression. Furthermore, using PDAC cell cultures, we found that interference of NF45 expression using siRNA oligos suppressed PDAC cell proliferation and retarded cell cycle progression. Moreover, depletion of NF45 impaired the levels of cellular cyclin E and proliferating cell nuclear antigen (PCNA). Conversely, overexpression of NF45 facilitated the cell growth and accelerated cell cycle progression. Our results establish NF45 as an important indicator of PDAC prognosis with potential utility as a therapeutic target in this lethal disease. PMID- 26276311 TI - Dextran-shelled oxygen-loaded nanodroplets reestablish a normoxia-like pro angiogenic phenotype and behavior in hypoxic human dermal microvascular endothelium. AB - In chronic wounds, hypoxia seriously undermines tissue repair processes by altering the balances between pro-angiogenic proteolytic enzymes (matrix metalloproteinases, MMPs) and their inhibitors (tissue inhibitors of metalloproteinases, TIMPs) released from surrounding cells. Recently, we have shown that in human monocytes hypoxia reduces MMP-9 and increases TIMP-1 without affecting TIMP-2 secretion, whereas in human keratinocytes it reduces MMP-2, MMP 9, and TIMP-2, without affecting TIMP-1 release. Provided that the phenotype of the cellular environment is better understood, chronic wounds might be targeted by new oxygenating compounds such as chitosan- or dextran-shelled and 2H,3H decafluoropentane-cored oxygen-loaded nanodroplets (OLNs). Here, we investigated the effects of hypoxia and dextran-shelled OLNs on the pro-angiogenic phenotype and behavior of human dermal microvascular endothelium (HMEC-1 cell line), another cell population playing key roles during wound healing. Normoxic HMEC-1 constitutively released MMP-2, TIMP-1 and TIMP-2 proteins, but not MMP-9. Hypoxia enhanced MMP-2 and reduced TIMP-1 secretion, without affecting TIMP-2 levels, and compromised cell ability to migrate and invade the extracellular matrix. When taken up by HMEC-1, nontoxic OLNs abrogated the effects of hypoxia, restoring normoxic MMP/TIMP levels and promoting cell migration, matrix invasion, and formation of microvessels. These effects were specifically dependent on time sustained oxygen diffusion from OLN core, since they were not achieved by oxygen free nanodroplets or oxygen-saturated solution. Collectively, these data provide new information on the effects of hypoxia on dermal endothelium and support the hypothesis that OLNs might be used as effective adjuvant tools to promote chronic wound healing processes. PMID- 26276312 TI - Co-administration of alpha-lipoic acid and cyclosporine aggravates colon ulceration of acetic acid-induced ulcerative colitis via facilitation of NO/COX 2/miR-210 cascade. AB - In this work, alpha-lipoic acid and cyclosporine demonstrated significant protection against acetic acid-induced ulcerative colitis in rats. We proposed that alpha-lipoic acid and cyclosporine co-administration might modulate their individual effects. Induction of ulcerative colitis in rats was performed by intra-rectal acetic acid (5% v/v) administration for 3 consecutive days. Effects of individual or combined used of alpha-lipoic acid (35 mg/kg ip) or cyclosporine (5mg/kg sc) for 6 days starting 2 days prior to acetic acid were assessed. Acetic acid caused colon ulceration, bloody diarrhea and weight loss. Histologically, there was mucosal atrophy and inflammatory cells infiltration in submucosa, associated with depletion of colon reduced glutathione, superoxide dismutase and catalase activities and elevated colon malondialdehyde, serum C-reactive protein (C-RP) and tumor necrosis factor-alpha (TNF-alpha). Colon gene expression of cyclooxygenase-2 and miR-210 was also elevated. These devastating effects of acetic acid were abolished upon concurrent administration of alpha-lipoic acid. Alternatively, cyclosporine caused partial protection against acetic acid-induced ulcerative colitis. Cyclosporine did not restore colon reduced glutathione, catalase activity, serum C-RP or TNF-alpha. Unexpectedly, co-administration of alpha-lipoic acid and cyclosporine aggravated colon ulceration. Concomitant use of alpha-lipoic acid and cyclosporine significantly increased nitric oxide production, cyclooxygenase-2 and miR-210 gene expression compared to all other studied groups. The current findings suggest that facilitation of nitric oxide/cyclooxygenase-2/miR-210 cascade constitutes, at least partially, the cellular mechanism by which concurrent use of alpha-lipoic acid and cyclosporine aggravates colon damage. Collectively, the present work highlights the probable risk of using alpha-lipoic acid/cyclosporine combination in ulcerative colitis patients. PMID- 26276313 TI - Biphasic reactions in patients with anaphylaxis treated with corticosteroids. AB - BACKGROUND: Although the incidence of anaphylaxis is rapidly increasing, the clinical characteristics and associated factors of a biphasic reaction are unclear. OBJECTIVE: To determine the incidence and clinical characteristics of biphasic reactions in patients with anaphylaxis treated with corticosteroids. METHODS: A total of 655 patients with anaphylaxis visiting the emergency department of a tertiary teaching hospital from January 2007 through December 2014 were analyzed. Patient characteristics, triggers, symptoms and signs, in hospital management, and disposition were recorded. A biphasic reaction was defined as the development of anaphylaxis after complete resolution of the initial reaction without further exposure to the offending agent within 7 days. Univariate and multivariate analyses on the predictors of the biphasic reaction were performed. RESULTS: Of the 415 patients with anaphylaxis treated with corticosteroids, 9 patients (2.2%) developed a biphasic reaction. The mean age was 48.4 years, and 221 patients (54.4%) were women. The median time from complete resolution of initial clinical symptoms to occurrence of the biphasic reaction was 15 hours (range 1-45). History of drug anaphylaxis (odds ratio 14.3, 95% confidence interval 2.4-85.8) was a contributing factor to the development of the biphasic reaction. CONCLUSION: The incidence of biphasic reactions was 2.2% in patients treated with corticosteroids and those with a history of drug anaphylaxis were at greater risk. PMID- 26276314 TI - Antisense-mediated affinity purification of dengue virus ribonucleoprotein complexes from infected cells. AB - The identification of RNA-binding proteins that physically associate with viral RNA molecules during infection can provide insight into the molecular mechanisms of RNA virus replication. Until recently, such RNA-protein interactions have been identified predominantly with the use of in vitro assays that may not accurately reflect associations that occur in the context of a living cell. Here we describe a method for the specific affinity purification of dengue virus RNA and associated proteins using in vivo cross-linking followed by antisense-mediated affinity purification. RNA-binding proteins that specifically co-purify with viral RNA using this method can be identified en masse by mass spectrometry. This strategy can potentially be adapted to the purification of any viral RNA species of interest. PMID- 26276315 TI - Protein ligand-binding site comparison by a reduced vector representation derived from multidimensional scaling of generalized description of binding sites. AB - Proteins serve various functions in living cells. When they exert their functions, physical contact with other molecules occurs. A close connection therefore exists between their functions and structures. Therefore, comparison and classification about known and predicted protein structures provides important insight into the structural features of proteins, elucidating their functions and structures. Analyzing the mutual interactions between proteins and small molecules is important to predict the ligands which bind to parts of putative ligand binding sites. Such analysis demands a fast and efficient method for comparing ligand binding sites because of the recent increase of protein structure information. A method has been developed for representing a ligand binding site with one reduced vector for binding site comparison. Using our method, one can calculate the similarity between ligand binding sites merely by calculating the inner product of 11-dimensional vectors. The method explained herein shows higher performance of the similarity between binding sites than metrics used in existing alignment-free methods. It also shows performance that is comparable to accurate methods developed recently, which employ solving the optimization problem: APoc. Moreover, these study results suggest that this new method can provide similarities faster than our previous method. PMID- 26276318 TI - Edge-Catalyst Wetting and Orientation Control of Graphene Growth by Chemical Vapor Deposition Growth. AB - Three key positions of graphene on a catalyst surface can be identified based on precise computations, namely as sunk (S), step-attached (SA), and on-terrace (OT). Surprisingly, the preferred modes are not all alike but vary from metal to metal, depending on the energies of graphene-edge "wetting" by the catalyst: on a catalyst surface of soft metal like Au(111), Cu(111) or Pd(111), the graphene tends to grow in step-attached or embedded mode, while on a rigid catalyst surface such as Pt(111), Ni(111), Rh(111), Ir(111), or Ru(0001), graphene prefers growing as step-attached or on-terrace. Accordingly, as further energy analysis shows, the graphene formed via the S and SA modes should have orientations fixed relative to the metal crystal lattice, thus prescribing epitaxial growth of graphene on Au(111), Cu(111) and Pd(111). This conclusion indeed correlates well with numerous experimental data, also solving some puzzles observed, and suggesting better ways for growing larger-area single-crystalline graphene by making proper catalyst selections. PMID- 26276316 TI - Biogeography of the Phalaenopsis amabilis species complex inferred from nuclear and plastid DNAs. AB - BACKGROUND: Phalaenopsis is one of the important commercial orchids in the world. Members of the P. amabilis species complex represent invaluable germplasm for the breeding program. However, the phylogeny of the P. amabilis species complex is still uncertain. The Phalaenopsis amabilis species complex (Orchidaceae) consists of subspecies amabilis, moluccana, and rosenstromii of P. amabilis, as well as P. aphrodite ssp. aphrodite, P. ap. ssp. formosana, and P. sanderiana. The aims of this study were to reconstruct the phylogeny and biogeographcial patterns of the species complex using Neighbor Joining (NJ), Maxinum Parsimony (MP), Bayesian Evolutionary Analysis Sampling Trees (BEAST) and Reconstruct Ancestral State in Phylogenies (RASP) analyses based on sequences of internal transcribed spacers 1 and 2 from the nuclear ribosomal DNA and the trnH-psbA spacer from the plastid DNA. RESULTS: A pattern of vicariance, dispersal, and vicariance + dispersal among disjunctly distributed taxa was uncovered based on RASP analysis. Although two subspecies of P. aphrodite could not be differentiated from each other in dispersal state, they were distinct from P. amabilis and P. sanderiana. Within P. amabilis, three subspecies were separated phylogenetically, in agreement with the vicariance or vicariance + dispersal scenario, with geographic subdivision along Huxley's, Wallace's and Lydekker's Lines. Molecular dating revealed such subdivisions among taxa of P. amabilis complex dating back to the late Pleistocene. Population-dynamic analyses using a Bayesian skyline plot suggested that the species complex experienced an in situ range expansion and population concentration during the late Last Glacial Maximum (LGM). CONCLUSIONS: Taxa of the P. amabilis complex with disjunct distributions were differentiated due to vicariance or vicariance + dispersal, with events likely occurring in the late Pleistocene. Demographic growth associated with the climatic oscillations in the Wurm glacial period followed the species splits. Nevertheless, a subsequent population slowdown occurred in the late LGM due to extinction of regional populations. The reduction of suitable habitats resulted in geographic fragmenttation of the remaining taxa. PMID- 26276319 TI - Elementary Excitations of Superfluid Helium Droplets Probed by Ion Spectroscopy. AB - Electronic spectra of molecules in helium droplets reveal spectral features that are related to the elementary excitations of the superfluid helium environment. In order to determine to what extent the interaction strength of the molecule with the helium affects these excitations, the spectrum corresponding to the B(2)A" <- X (2)A" transition of 2,5-difluorophenol cations in helium droplets has been recorded. The vibronic resonances reveal a sharp zero-phonon line whose width is largely determined by the rotational band contour, followed by a broad structureless phonon wing at higher frequencies. The splitting between the zero phonon line and phonon wing is approximately half of that found for neutral 2,5 difluorophenol. This difference is attributed to the increased helium density around the ion due to its strong interaction with the helium. PMID- 26276320 TI - Trapped Abstraction in the O((1)D) + CHD3 -> OH + CD3 Reaction. AB - Despite significant progress made in past decades, it is still challenging to elucidate dynamics mechanisms for polyatomic reactions, in particular, involving complex formation. The reaction of O((1)D) with methane has long been regarded as a prototypical polyatomic system of direct insertion reaction in which the O((1)D) atom can insert into the C-H bond of methane to form a "hot" methanol intermediate before decomposition. Here, we report a combined theoretical and experimental study on the O((1)D) + CHD3 reaction, on which good agreement between theory and experiment is achieved. Our study revealed that this complex forming reaction actually proceeds via a trapped abstraction mechanism, rather than an insertion mechanism as has long been thought. We anticipate that this reaction mechanism should also be responsible for the reaction of O((1)D) with ethane and propane, as well as many other chemical reactions with deep wells in the interaction region. PMID- 26276321 TI - Plasmon-in-a-Box: On the Physical Nature of Few-Carrier Plasmon Resonances. AB - Recent demonstrations in doped semiconductor nanocrystals establish that a plasmon resonance can be sustained by a handful of charge carriers, much smaller in number than conventionally thought. This finding raises questions about the physical nature of such a collective resonance, a fundamental question in condensed matter and many-body physics, which the author addresses here by means of a plasmon-in-a-box model. A small number of carriers confined within a nanocrystal exhibit multiple transitions of individual carriers between quantized states. However, as carriers are progressively added, spectral lines associated with single-carrier excitations evolve into a band representing a collective resonance. This evolution is gradual, and it involves an intermediate regime where single-carrier excitations and few-carrier collective excitations coexist, until, at high carrier numbers, a purely classical collective resonance involving all carriers in the nanocrystal is sustained. The author finds that the emergence of the plasmon resonance is a density-driven transition; at high enough carrier densities, the Coulomb repulsion between carriers becomes strong enough to allow individual carriers to overcome their confinement to the nanocrystal lattice and to participate in a collective excitation within the mean Coulomb field of other carriers. The findings represent deeper insight into the physical picture of a plasmon resonance and serve as a potential design guide for nanoscale optoelectronic components and photocatalytic plasmonic clusters. PMID- 26276317 TI - Sex-Specific Effects of Adiponectin on Carotid Intima-Media Thickness and Incident Cardiovascular Disease. AB - BACKGROUND: Plasma adiponectin levels have previously been inversely associated with carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis. In this study, we used a sex-stratified Mendelian randomization approach to investigate whether adiponectin has a causal protective influence on IMT. METHODS AND RESULTS: Baseline plasma adiponectin concentration was tested for association with baseline IMT, IMT progression over 30 months, and occurrence of cardiovascular events within 3 years in 3430 participants (women, n=1777; men, n=1653) with high cardiovascular risk but no prevalent disease. Plasma adiponectin levels were inversely associated with baseline mean bifurcation IMT after adjustment for established risk factors (beta=-0.018, P<0.001) in men but not in women (beta=-0.006, P=0.185; P for interaction=0.061). Adiponectin levels were inversely associated with progression of mean common carotid IMT in men (beta=-0.0022, P=0.047), whereas no association was seen in women (0.0007, P=0.475; P for interaction=0.018). Moreover, we observed that adiponectin levels were inversely associated with coronary events in women (hazard ratio 0.57, 95% CI 0.37 to 0.87) but not in men (hazard ratio 0.82, 95% CI 0.54 to 1.25). A gene score of adiponectin-raising alleles in 6 loci, reported recently in a large multi-ethnic meta-analysis, was inversely associated with baseline mean bifurcation IMT in men (beta=-0.0008, P=0.004) but not in women (beta=-0.0003, P=0.522; P for interaction=0.007). CONCLUSIONS: This report provides some evidence for adiponectin protecting against atherosclerosis, with effects being confined to men; however, compared with established cardiovascular risk factors, the effect of plasma adiponectin was modest. Further investigation involving mechanistic studies is warranted. PMID- 26276322 TI - Understanding Adsorption-Induced Effects on Platinum Nanoparticles: An Energy Decomposition Analysis. AB - Platinum nanoparticle catalysts are used in a myriad of gas-phase, liquid-phase, and electrochemical reactions. Although a high catalytic activity is paramount, stability must also be guaranteed, especially when the nanoparticles are in contact with strongly bound adsorbates. Therefore, it is crucial to be able to accurately calculate adsorption-energy trends on Pt nanoparticles of multiple sizes and morphologies using ab initio methods at affordable computational expenses. Here, through an energy-decomposition analysis in which adsorption processes are regarded as the interplay between pure binding and various compensating core-shell deformations, we show that pure binding is responsible for the overall linear adsorption trends. Conversely, the energetic cost of the deformations is a site-independent, adsorbate-dependent constant value. These two observations and the description of the trends by means of generalized coordination numbers help to significantly reduce the computational expense of simulating large nanoparticles. PMID- 26276323 TI - Recent Advances in Tip-Enhanced Raman Spectroscopy. AB - Tip-enhanced Raman spectroscopy (TERS) has experienced tremendous growth in the last 5 years. Specifically, TER imaging has provided invaluable insight into the spatial distribution and properties of chemical species on a surface with spatial resolution that is otherwise unattainable by any other analytical method. Additionally, there has been further development in coupling ultrafast spectroscopy with TERS in the hope of obtaining both ultrafast temporal and nanometer-scale spatial resolution. In this Perspective, we discuss several recent advances in TERS, specifically highlighting those in the areas of TER imaging and integrating ultrafast spectroscopy with TERS. PMID- 26276324 TI - Different Types of Vibrations Interacting with Electronic Excitations in Phycoerythrin 545 and Fenna-Matthews-Olson Antenna Systems. AB - The interest in the phycoerythrin 545 (PE545) photosynthetic antenna system of marine algae and the Fenna-Matthews-Olson (FMO) complex of green sulfur bacteria has drastically increased since long-lived quantum coherences were reported for these complexes. For the PE545 complex, this phenomenon is clearly visible even at ambient temperatures, while for the FMO system it is more prominent at lower temperatures. The key to elucidate the role of the environment in these long lived quantum effects is the spectral density. Here, we employ molecular dynamics simulations combined with quantum chemistry calculations to study the coupling between the biological environment and the vertical excitation energies of the bilin pigment molecules in PE545 and compare them to prior calculations on the FMO complex. It is found that the overall strength of the resulting spectral densities for the PE545 system is similar to the experiment-based counterpart but also to those in the FMO complex. Molecular analysis, however, reveals that the origin for the spectral densities in the low frequency range, which is most important for excitonic transitions, is entirely different. In the case of FMO, this part of the spectral density is due to environmental fluctuations, while, in case of PE545, it is essentially only due to internal modes of the bilin molecules. This finding sheds new light on possible explanations of the long lived quantum coherences and that the reasons might actually be different in dissimilar systems. PMID- 26276325 TI - Vibrational Excitation in Electron Transport through Carbon Nanotube Quantum Dots. AB - Electron transport in single-walled carbon nanotubes (SWCNTs) is extremely sensitive to environmental effects. SWCNTs experiencing an inhomogeneous environment are effectively subjected to a disorder potential, which can lead to localized electronic states. An important element of the physical picture of such states localized on the nanometer-scale is the existence of a local vibronic mainfold resulting from the localization-enhanced electron-vibrational coupling. In this Letter, scanning tunneling spectroscopy (STS) is used to study the quantum-confined electronic states in SWCNTs deposited on the Au(111) surface. STS spectra show the vibrational overtones identified as D-band Kekule vibrational modes and K-point transverse out-of plane phonons. The presence of these vibrational modes in the STS spectra suggests rippling distortion and dimerization of carbon atoms on the SWCNT surface. The present study thus, for the first time, experimentally connects the properties of well-defined localized electronic states to the properties of their associated vibronic states. PMID- 26276326 TI - Prediction of Superhalogen-Stabilized Noble Gas Compounds. AB - The discovery of HArF has generated renewed interest in the chemistry of noble gases, particularly their hydrides. Though many weak complexes of noble gases bound by van der Waals interactions are known, the number of halogenated noble gas compounds, HNgX (Ng = noble gas; X = halogen), where the noble gas atom is chemically bound, is limited. These molecules are metastable, and their specialty is that there is substantial ionic bonding between the noble gas atom and the halogen atom. In this Letter, it is shown using density functional theory and second-order Moller-Plesset perturbation theory that by replacing the halogen atoms by superhalogens (Y), whose electron affinities are much larger than those of halogens, more ionic bonds between Ng and Y can be attained. Moreover, the superhalogen-containing noble gas hydrides, HNgY, are more stable compared to their halogenated counterparts. PMID- 26276327 TI - Design and Observation of Biphase TiO2 Crystal with Perfect Junction. AB - Bicrystalline materials have wide applications from silicon chips to photocatalysis, but the controlled synthesis of nanocrytals with ordered phase junction has been challenging, in particular via chemical synesthetic routes. Here, we propose a general strategy to design biphase crystals formed via partial solid-to-solid phase transition with perfect phase junction, e.g., being atomically sharp and built of two particular sets of epitaxially joined planes of the two component phases, and present such an example by designing, synthesizing, and characterizing the interface of two TiO2 phases, namely, TiO2-B/anatase biphase nanocrystals that are obtained conveniently via one-pot chemical synthesis. Our design strategy classifies the common solid-to-solid phase transition into three types that are distinguishable by using the newly developed stochastic surface walking (SSW) method for unbiased pathway sampling. Only Type I crystal is predicted to possess perfect phase junction, where the phase transition involves one and only one propagation direction featuring single pathway phase transition containing only one elementary kinetic step. The method is applicable for the understanding and the design of heterophase materials via partial phase transition in general. PMID- 26276328 TI - Efficient Carrier Multiplication in Colloidal CuInSe2 Nanocrystals. AB - Transient absorption spectroscopy (TAS) was used to study carrier multiplication (CM) (also called multiexciton generation (MEG)) in solvent-dispersed colloidal CuInSe2 nanocrystals with diameters as small as 4.5 nm. Size-dependent carrier cooling rates, absorption cross sections, and Auger lifetimes were also determined. The energy threshold for CM in the CuInSe2 nanocrystals was found to be 2.4 +/- 0.2 times the nanocrystal energy gap (Eg) and the CM efficiency was 36 +/- 6% per unit Eg. This is similar to other types of nanocrystal quantum dot materials. PMID- 26276329 TI - Hierarchy of Chemical Bonding in the Synthesis of Fe-Phthalocyanine on Metal Surfaces: A Local Spectroscopy Approach. AB - Scanning tunneling spectroscopy (STS) has become a key tool for accessing properties of organometallic molecules adsorbed on surfaces. However, the rich variety of signatures makes it sometimes a difficult task to find out which feature is intrinsic to the molecule, i.e., relevant for a metal-ligand interaction or related to the interaction of the molecule with the substrate. Here we study the prototype covalent self-assembly of FePc and probe how electronic/magnetic properties at the local scale change as a function of temperature-induced step-by-step assembly, starting from TCNB (1,2,4,5- Tetracyanobenzene) molecular and Fe atomic precursors. Intermediate complexes with tetra-coordinated Fe atoms are then used both, as synthons for the FePc and as identifiers of specific features of the STS. As observed by STS and confirmed by spin-polarized DFT calculations, the occupied dpi states of Fe are present in both the FePc and Fe(TCNB)2 on Au(111). The main difference appears in the dz(2) states, which play a key role in magnetism as confirmed by the presence/absence of the Kondo resonance. A comprehensive picture is obtained by following with STS the hybridization of the dz(2) orbital of Fe to various substrates (Cu, Au and Co). Finally it is demonstrated that FePc units can be created by on-surface polymerization from the Fe(TCNB)2 network upon thermal annealing. PMID- 26276330 TI - Capturing the Local Adsorption Structures of Carbon Dioxide in Polyamine Impregnated Mesoporous Silica Adsorbents. AB - Interactions between amines and carbon dioxide (CO2) are essential to amine functionalized solid adsorbents for carbon capture, and an in-depth knowledge of these interactions is crucial to adsorbent design and fabrication as well as adsorption/desorption processes. The local structures of CO2 adsorbed on a tetraethylenepentamine-impregnated mesoporous silica SBA-15 were investigated by solid-state (13)C{(14)N} S-RESPDOR MAS NMR technique and theoretical DFT calculations. Two types of adsorption species, namely, secondary and tertiary carbamates as well as distant ammonium groups were identified together with their relative concentrations and relevant (14)N quadrupolar parameters. Moreover, a dipolar coupling of 716 Hz was derived, corresponding to a (13)C-(14)N internuclear distance of 1.45 A. These experimental data are in excellent agreement with results obtained from DFT calculations, revealing that the distribution of surface primary and secondary amines readily dictates the CO2 adsorption/desorption properties of the adsorbent. PMID- 26276331 TI - Ion Mobility Unlocks the Photofragmentation Mechanism of Retinal Protonated Schiff Base. AB - Retinal protonated Schiff base (RPSB) is a key molecular component of biological photoreceptors and bacterial photosynthetic structures, where its action involves photoisomerization around bonds in the polyene chain. In a vacuum environment, collisional activation or exposure to visible light causes the RPSB molecule to disintegrate, producing charged molecular fragments with m/z = 248 Da that cannot be formed by simple cleavage of the polyene chain. Photofragments resulting from laser excitation of RPSB at a wavelength of 532 nm are analyzed in an ion mobility mass spectrometer (IMMS) and found to be the protonated Schiff base of beta-ionone. Density functional theory calculations at the M06-2X/cc-pVDZ level support a fragmentation mechanism in which RPSB undergoes an electrocyclization/fragmentation cascade with the production of protonated Schiff base of beta-ionone and toluene. PMID- 26276332 TI - Donor-Bridge-Acceptor Proton Transfer in Aqueous Solution. AB - We use ab initio molecular dynamics to study proton transfer in a donor-bridge acceptor system in which the bridge is a single water molecule and the entire system is embedded in aqueous solution. The results, based on a large number of proton transfer trajectories, demonstrate that the dominant charge-transfer pathway is a subpicosecond "through bridge" event in which the bridge adopts an Eigen-like (hydronium) structure. We also identify another state in which the bridge forms a Zundel-like configuration with the acceptor that appears to be a dead end for the charge transfer. The reaction coordinate is inherently multidimensional and, as we demonstrate, cannot be given in terms of either local structural parameters of the donor-bridge-acceptor system or local solvent coordination numbers. PMID- 26276333 TI - Surface Termination of the Metal-Organic Framework HKUST-1: A Theoretical Investigation. AB - The surface morphology and termination of metal-organic frameworks (MOF) is of critical importance in many applications, but the surface properties of these soft materials are conceptually different from those of other materials like metal or oxide surfaces. Up to now, experimental investigations are scarce and theoretical simulations have focused on the bulk properties. The possible surface structure of the archetypal MOF HKUST-1 is investigated by a first-principles derived force field in combination with DFT calculations of model systems. The computed surface energies correctly predict the [111] surface to be most stable and allow us to obtain an unprecedented atomistic picture of the surface termination. Entropic factors are identified to determine the preferred surface termination and to be the driving force for the MOF growth. On the basis of this, reported strategies like employing "modulators" during the synthesis to tailor the crystal morphology are discussed. PMID- 26276334 TI - Experimental Determination of the Electrostatic Nature of Carbonyl Hydrogen Bonding Interactions Using IR-NMR Correlations. AB - Hydrogen-bonding plays a fundamental role in the structure, function, and dynamics of various chemical and biological systems. Understanding the physical nature of interactions and the role of electrostatics in hydrogen-bonding has been the focus of several theoretical and computational research. We present an experimental approach involving IR-(13)C NMR correlations to determine the electrostatic nature of carbonyl hydrogen-bonding interactions. This report provides a direct experimental evidence of the classical nature of hydrogen bonding interaction in carbonyls, independent of any theoretical approximation. These results have important implications in chemistry and biology and can be applied to probe the reaction mechanisms involving carbonyl activation/stabilization by hydrogen bonds using spectroscopic techniques. PMID- 26276335 TI - Accurate Identification and Selective Removal of Rotavirus Using a Plasmonic Magnetic 3D Graphene Oxide Architecture. AB - According to the World Health Organization, even in the 21st century, more than one million children die each year due to the rotavirus contamination of drinking water. Therefore, accurate identification and removal of rotavirus are very important to save childrens' lives. Driven by the need, in this Letter, we report for the first time highly selective identification and removal of rotavirus from infected water using a bioconjugated hybrid graphene oxide based three dimensional (3D) solid architecture. Experimental results show that due to the presence of a high intensity of "hot spots" in the 3D network, an antibody attached 3D plasmonic-magnetic architecture can be used for accurate identification of rotavirus using surface-enhanced Raman spectroscopy (SERS). Reported data demonstrate that the antibody-attached 3D network binds strongly with rotavirus and is capable of highly efficient removal of rotavirus, which has been confirmed by SERS, fluorescence imaging, and enzyme-linked immunosorbent assay (ELISA) data. We discuss a possible mechanism for accurate identification and efficient removal of rotavirus from infected drinking water. PMID- 26276336 TI - Using Molecular Design to Control the Performance of Hydrogen-Producing Polymer Brush-Modified Photocathodes. AB - Attachment of difluoroborylcobaloxime catalysts to a polymer-brush-modified GaP semiconductor allows improved hydrogen production levels and photoelectrochemical performance under aqueous acidic conditions (pH = 4.5) as compared to the performance of electrodes without catalyst treatment. The catalytic assembly used in this work incorporates a boron difluoride (BF2) capping group on the glyoximate ligand of the catalyst, a synthetic modification previously used to enhance the stability of nonsurface-attached complexes toward acid hydrolysis and to shift the cobalt reduction potentials of the complex to less negative, and thus technologically more relevant, values. The pH-dependent photoresponses of the cobaloxime- and difluoroborylcobaloxime- modified semiconductors are shown to be consistent with those from analogous studies using non-surface-attached cobaloxime catalysts as well as catalysts supported on conductive electrodes. Thus, this work illustrates the potential to control and optimize the properties of visible-light-absorbing semiconductors using polymeric overcoating techniques coupled with the principles of synthetic molecular design. PMID- 26276337 TI - On Universality in Sputtering Yields Due to Cluster Bombardment. AB - Molecular dynamics simulations, in which atomic and molecular solids are bombarded by Arn (n = 60-2953) clusters, are used to explain the physics that underlie the "universal relation" of the sputtering yield Y per cluster atom versus incident energy E per cluster atom (Y/n vs E/n). We show that a better representation to unify the results is Y/(E/U0) versus (E/U0)/n, where U0 is the sample cohesive energy per atom or molecular equivalent, and the yield Y is given in the units of atoms or molecular equivalents for atomistic and molecular solids, respectively. In addition, we identified a synergistic cluster effect. Specifically, for a given (E/U0)/n value, larger clusters produce larger yields than the yields that are only proportional to the cluster size n or equivalently to the scaled energy E/U0. This synergistic effect can be described in the high (E/U0)/n regime as scaling of Y with (E/U0)(alpha), where alpha > 1. PMID- 26276338 TI - Femtosecond Pump-Push-Probe and Pump-Dump-Probe Spectroscopy of Conjugated Polymers: New Insight and Opportunities. AB - Conjugated polymers are an important class of soft materials that exhibit a wide range of applications. The excited states of conjugated polymers, often referred to as excitons, can either deactivate to yield the ground state or dissociate in the presence of an electron acceptor to form charge carriers. These interesting properties give rise to their luminescence and the photovoltaic effect. Femtosecond spectroscopy is a crucial tool for studying conjugated polymers. Recently, more elaborate experimental configurations utilizing three optical pulses, namely, pump-push-probe and pump-dump-probe, have been employed to investigate the properties of excitons and charge-transfer states of conjugated polymers. These studies have revealed new insight into femtosecond torsional relaxation and detrapping of bound charge pairs of conjugated polymers. This Perspective highlights (1) the recent achievements by several research groups in using pump-push-probe and pump-dump-probe spectroscopy to study conjugated polymers and (2) future opportunities and potential challenges of these techniques. PMID- 26276339 TI - Hole-Conductor-Free, Metal-Electrode-Free TiO2/CH3NH3PbI3 Heterojunction Solar Cells Based on a Low-Temperature Carbon Electrode. AB - Low cost, high efficiency, and stability are straightforward research challenges in the development of organic-inorganic perovskite solar cells. Organolead halide is unstable at high temperatures or in some solvents. The direct preparation of a carbon layer on top becomes difficult. In this study, we successfully prepared full solution-processed low-cost TiO2/CH3NH3PbI3 heterojunction (HJ) solar cells based on a low-temperature carbon electrode. Power conversion efficiency of mesoporous (M-)TiO2/CH3NH3PbI3/C HJ solar cells based on a low-temperature processed carbon electrode achieved 9%. The devices of M-TiO2/CH3NH3PbI3/C HJ solar cells without encapsulation exhibited advantageous stability (over 2000 h) in air in the dark. The ability to process low-cost carbon electrodes at low temperature on top of the CH3NH3PbI3 layer without destroying its structure reduces the cost and simplifies the fabrication process of perovskite HJ solar cells. This ability also provides higher flexibility to choose and optimize the device, as well as investigate the underlying active layers. PMID- 26276340 TI - Thermoelectricity in Disordered Organic Semiconductors under the Premise of the Gaussian Disorder Model and Its Variants. AB - Using Monte Carlo simulations, we investigate the thermoelectric properties of disordered organic semiconductors under the premise of the Gaussian disorder model and its variants. In doing so, we provide much needed additional dimensions for comparison between these theoretical frameworks and real systems beyond those based on extensively studied charge-transport properties and aim to provide a frame-of-reference for rising interest in these systems for thermoelectric-based applications. To illustrate the potential existing in the implementation of combined transport and thermoelectric investigation, we discuss strategies to experimentally deduce a system's DOS shape and the temperature dependence of its transport energy (which can discern hopping transport from multiple trapping transport), infer whether a system's activation energy originates from inherent energetic disorder or a polaron activation energy (while deducing the given polaron activation energy), and discerning whether a system's energetic disorder is spatially correlated or accompanied by off-diagonal disorder. PMID- 26276341 TI - Observation of the Early Structural Changes Leading to the Formation of Protein Superstructures. AB - Formation of superstructures in protein aggregation processes has been indicated as a general pathway for several proteins, possibly playing a role in human pathologies. There is a severe lack of knowledge on the origin of such species in terms of both mechanisms of formation and structural features. We use equine lysozyme as a model protein, and by combining spectroscopic techniques and microscopy with X-ray fiber diffraction and ab initio modeling of Small Angle X ray Scattering data, we isolate the partially unfolded state from which one of these superstructures (i.e., particulate) originates. We reveal the low resolution structure of the unfolded state and its mechanism of formation, highlighting the physicochemical features and the possible pathway of formation of the particulate structure. Our findings provide a novel detailed knowledge of such a general and alternative aggregation pathway for proteins, this being crucial for a basic and broader understanding of the aggregation phenomena. PMID- 26276342 TI - Excitation Spectra and Stokes Shift Measurements of Single Organic Dyes at Room Temperature. AB - We report measurements of excitation and emission spectra of single, polymer embedded, perylene dye molecules at room temperature. From these measurements, we can derive the Stokes shift for each single molecule. We determined the distribution of excitation and emission peak energies and, thus, the distribution of single molecule Stokes shifts. Single molecule Stokes shifts have not been recorded to date, and the Stokes shift has often been assumed to be constant in single molecule studies. Our data show that the observed spectral heterogeneity in single molecule emission originates not only from synchronous energetic shifts of the excitation and the emission spectra but also from variations in the Stokes shift, speaking against the assumption of constant Stokes shift. PMID- 26276343 TI - Electric Fields Control TiO2(e(-)) + I3(-) -> Charge Recombination in Dye Sensitized Solar Cells. AB - The electric fields generated by excited-state electron injection into anatase TiO2 nanocrystallites are screened by cations present in the external electrolyte. With some assumptions, a newly discovered electroabsorption signature enables quantification of the electric field strength experienced by surface-anchored dye molecules. Here, it was found that the fields increased in the order Na(+) < Li(+) < Mg(2+) < Ca(2+), with magnitudes of 1.1 MV/cm for Na(+) and 2.2 MV/cm for Ca(2+), values that were insensitive to whether the anion was iodide or perchlorate. The magnitude of the field was directly related to average TiO2(e(-)) + I3(-) -> charge recombination rate constants abstracted from time resolved kinetic data. Extrapolation to zero field provided an estimate of recombination dynamics when diffusion alone controlled I3(-) mass transport, k = 300 s(-1). The decreased rate constants measured after excited-state injection were attributed to migration of I3(-) away from the TiO2. Cation transference coefficients were tabulated that ranged from t = 0.97 for Ca(2+) to 0.40 for Na(+) and represented the ability of the unscreened electric field to block the TiO2(e(-)) + I3(-) -> charge recombination reaction. This data provides the first compelling evidence that the anionic nature of I3(-) inhibits unwanted charge recombination in dye-sensitized solar cells. PMID- 26276344 TI - Observing Vibrational Energy Flow in a Protein with the Spatial Resolution of a Single Amino Acid Residue. AB - One of the challenges in physical chemistry has been understanding how energy flows in a condensed phase from the microscopic viewpoint. To address this, space resolved information at the molecular scale is required but has been lacking due to experimental difficulties. We succeeded in the real-time mapping of the vibrational energy flow in a protein with the spatial resolution of a single amino acid residue by combining time-resolved resonance Raman spectroscopy and site-directed single-Trp mutagenesis. Anti-Stokes Raman intensities of the Trp residues at different sites exhibited different temporal evolutions, reflecting propagation of the energy released by the heme group. A classical heat transport model was not able to reproduce the entire experimental data set, showing that we need a molecular-level description to explain the energy flow in a protein. The systematic application of our general methodology to proteins with different structural motifs may provide a greatly increased understanding of the energy flow in proteins. PMID- 26276345 TI - Submolecular Spectroscopy? PMID- 26276346 TI - In vitro properties of hordeivirus TGB1 protein forming ribonucleoprotein complexes. AB - Hordeivirus movement protein encoded by the first gene of the triple gene block (TGB1 protein, TGBp1) interacts in vivo with viral genomic and subgenomic RNAs to form ribonucleoprotein (RNP) particles that are considered to be a form of viral genome (non-virion transport form) capable of cell-to-cell and long-distance transport in infected plants. The structures of these RNPs have not been elucidated. The poa semilatent virus (PSLV) TGBp1 contains a structured C terminal NTPase/helicase domain and an N-terminal extension region consisting of two domains - a completely intrinsically disordered extreme N-terminal domain and an internal domain (ID) with structure resembling a partially disordered molten globule. Here, we characterized the structures assembled in vitro by the full length PSLV TGBp1 alone or in the presence of viral RNA. The PSLV TGBp1 was capable of multimerization and self-assembly into extended high-molecular-mass complexes. These complexes disassembled to apparent monomers upon incubation with ATP. Upon incubation with viral RNA, the PSLV TGBp1 in vitro formed RNP structures that appeared as filamentous particles resembling virions of helical filamentous plant viruses in morphology and dimensions. By comparing the biophysical characteristics of PSLV TGBp1 and its domains in the presence and absence of RNA, we show that the ID plays the main structural role in the self interactions and RNA interactions of TGBp1 leading to the assembly of virus-like RNP particles. PMID- 26276347 TI - An international internet survey of the experiences of 1,714 mothers with a late stillbirth: the STARS cohort study. AB - BACKGROUND: Stillbirth occurring after 28 weeks gestation affects between 1.5-4.5 per 1,000 births in high-income countries. The majority of stillbirths in this setting occur in women without risk factors. In addition, many established risk factors such as nulliparity and maternal age are not amenable to modification during pregnancy. Identification of other risk factors which could be amenable to change in pregnancy should be a priority in stillbirth prevention research. Therefore, this study aimed to utilise an online survey asking women who had a stillbirth about their pregnancy in order to identify any common symptoms and experiences. METHODS: A web-based survey. RESULTS: A total of 1,714 women who had experienced a stillbirth >3 weeks prior to enrolment completed the survey. Common experiences identified were: perception of changes in fetal movement (63% of respondents), reports of a "gut instinct" that something was wrong (68%), and perceived time of death occurring overnight (56%). A quarter of participants believed that their baby's death was due to a cord issue and another 18% indicated that they did not know the reason why their baby died. In many cases (55%) the mother believed the cause of death was different to that told by clinicians. CONCLUSIONS: This study confirms the association between altered fetal movements and stillbirth and highlights novel associations that merit closer scrutiny including a maternal gut instinct that something was wrong. The potential importance of maternal sleep is highlighted by the finding of more than half the mothers believing their baby died during the night. This study supports the importance of listening to mothers' concerns and symptoms during pregnancy and highlights the need for thorough investigation of stillbirth and appropriate explanation being given to parents. PMID- 26276348 TI - A method for in vitro regional aerosol deposition measurement in a model of the human tracheobronchial tree by the positron emission tomography. AB - Researchers have been studying aerosol transport in human lungs for some decades. The overall lung deposition can be predicted with sufficient precision nowadays. However, the prediction of local deposition remains an unsolved problem. Numerical modeling of aerosol transport can provide detailed data with such precision and spatial resolution which were unavailable in the past. Yet, the necessary validation of numerical results represents a difficult task, as the experimental data in a sufficient spatial resolution are hardly available. This article introduces a method based on positron emission tomography, which allows acquisition of detailed experimental data on local aerosol deposition in a realistic model of human lungs. The method utilizes the Condensation Monodisperse Aerosol Generator modified for a safe production of radioactive aerosol particles and a special measuring rig. The scanning of the model is performed on a positron emission tomography-computed tomography scanner. The evaluation of aerosol deposition is based on a volume radioactivity analysis in a specialized, yet publicly available software. The reliability of the method was tested and its first results are discussed in the article. The measurements performed using the presented method can serve for validation of numerical simulations, since the presented lung model digital geometry is available. PMID- 26276349 TI - Pro-cognitive activity in rats of 3-furan-2-yl-N-p-tolyl-acrylamide, a positive allosteric modulator of the alpha7 nicotinic acetylcholine receptor. AB - BACKGROUND AND PURPOSE: alpha7 nicotinic acetylcholine receptors (alpha7 nAChRs) may represent useful targets for cognitive improvement. The aim of this study is to compare the pro-cognitive activity of selective alpha7-nAChR ligands, including the partial agonists, DMXBA and A-582941, as well as the positive allosteric modulator, 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2). EXPERIMENTAL APPROACH: The attentional set-shifting task (ASST) and the novel object recognition task (NORT) in rats, were used to evaluate the pro-cognitive activity of each ligand [i.e., PAM-2 (0.5, 1.0, and 2.0 mg.kg(-1) ), DMXBA and A-582941 (0.3 and 1.0 mg.kg(-1) )], in the absence and presence of methyllycaconitine (MLA), a selective competitive antagonist. To determine potential drug interactions, an inactive dose of PAM-2 (0.5 mg.kg(-1) ) was co-injected with inactive doses of either agonist - DMXBA: 0.1 (NORT); 0.3 mg.kg(-1) (ASST) or A 582941: 0.1 mg.kg(-1) . KEY RESULTS: PAM-2, DMXBA, and A-582941 improved cognition in a MLA-dependent manner, indicating that the observed activities are mediated by alpha7 nAChRs. Interestingly, the co-injection of inactive doses of PAM-2 and DMXBA or A-582941 also improved cognition, suggesting drug interactions. Moreover, PAM-2 reversed the scopolamine-induced NORT deficit. The electrophysiological results also support the view that PAM-2 potentiates the alpha7 nAChR currents elicited by a fixed concentration (3 MUM) of DMXBA with apparent EC50 = 34 +/- 3 MUM and Emax = 225 +/- 5 %. CONCLUSIONS AND IMPLICATIONS: Our results support the view that alpha7 nAChRs are involved in cognition processes and that PAM-2 is a novel promising candidate for the treatment of cognitive disorders. PMID- 26276351 TI - Effect of male body mass index on clinical outcomes following assisted reproductive technology: a meta-analysis. AB - Overweight and obese males might exhibit a great risk of infertility. However, according to the current studies, the association between elevated male body mass index (BMI) and the clinical adverse results after assisted reproductive technology (ART) remains controversial. Hence, we conducted a meta-analysis to evaluate the effects of raised male BMI on clinical outcomes following ART. PubMed, EMBASE and three Chinese databases were used to identify relevant studies. The primary outcome was clinical pregnancy rate. Secondary outcomes included live birth rate and sperm parameters. A total of 5262 male participants from 10 cohort studies were subjected to meta-analysis. Results indicated that overweight or obese had no significant impact on clinical pregnancy rate [in vitro fertilisation (IVF): odds ratio (OR), 0.73; 95% confidence interval (CI), 0.39-1.39; intracytoplasmic sperm injection (ICSI): OR, 1.03; 95% CI, 0.92-1.15], live birth rate (IVF: OR, 0.91; 95% CI, 0.78-1.06; ICSI: OR, 1.00; 95% CI, 0.50 1.99) and sperm concentration (SMD, -0.28; 95% CI, -0.65 to 0.08) compared with normal weight following IVF/ICSI treatments. Exclusion of any single study and almost all the sensitivity analyses showed that our results were reliable. At present, the role of male BMI in the process of ART is only partly understood and should be further investigated. PMID- 26276350 TI - Studying longitudinal trajectories in animal models of psychiatric illness and their translation to the human condition. AB - Many forms of psychopathology and/or psychiatric illness can occur through the pathways of altered environmental sensitivity, impulsivity, social functioning, and anxious responding. While these traits are also heritable, environmental conditions are known to play a critical role. The genetic factors that contribute to these traits may be adaptive in certain contexts, but can - under the environmental conditions commonly faced among modern humans - also be key moderators of risk for psychopathological outcomes. This article will discuss how animal studies inform us of the various environmental mechanisms through which prenatal or early postnatal environmental challenge can produce long-term effects on behavior and will briefly address how pre-copulatory, pre-natal and early postnatal epigenetic effects can contribute to persistent alterations in offspring behavior. Its main focus will be how nonhuman primate studies have helped us to understand how genetic vulnerability factors can moderate responses to early environmental factors, suggesting pathways through which early stress might produce long-term effects, thus pointing to systems that might moderate risk for psychiatric illnesses in humans. PMID- 26276352 TI - PTEN and NEDD4 in Human Breast Carcinoma. AB - PTEN is an important tumor suppressor gene that antagonizes the oncogenic PI3K/AKT signaling pathway and has functions in the nucleus for maintaining genome integrity. Although PTEN inactivation by mutation is infrequent in breast cancer, transcript and protein levels are deficient in >25 % of cases. The E3 ubiquitin ligase NEDD4 (also known as NEDD4-1) has been reported to negatively regulate PTEN protein levels through poly-ubiquitination and proteolysis in carcinomas of the prostate, lung, and bladder, but its effect on PTEN in the breast has not been studied extensively. To investigate whether NEDD4 contributes to low PTEN levels in human breast cancer, we analyzed the expression of these proteins by immunohistochemistry across a large Swedish cohort of breast tumor specimens, and their transcript expression levels by microarrays. For both NEDD4 and PTEN, their transcript expression was significantly correlated to their protein expression. However, comparing NEDD4 expression to PTEN expression, either no association or a positive correlation was observed at the protein and transcript levels. This unexpected observation was further corroborated in two independent breast cancer cohorts from The Netherlands Cancer Institute and The Cancer Genome Atlas. Our results suggest that NEDD4 is not responsible for the frequent down-regulation of the PTEN protein in human breast carcinoma. PMID- 26276353 TI - Mitochondrial D310 mutation as clonal marker for solid tumors. AB - Patients with multiple tumors, either synchronous or metachronous, can have metastatic disease or suffer from multiple independent primary tumors. While proper diagnosis of these patients is important for prognosis and treatment, this can be challenging using only clinical and histological criteria. The aim of the present study was to evaluate the value of mitochondrial D310 mutation analysis in diagnostic questions regarding tumor clonality for a wide range of tumor types. Sanger sequencing of D310 was performed on a diagnostic cohort of 382 patients with 857 tumors that were previously analyzed using routine molecular analysis on genomic DNA. The D310 mononucleotide repeat was frequently somatically mutated (56/321, 17 %) in several tumor types, including breast, head and neck, gynecological, lung, colorectal, and skin tumors. For 84/327 (26 %) patients, a D310 mutation was detected in at least one of their tumors; for these patients, D310 can be used to determine the clonal relationship between their multiple tumors. Clonality assessments based on mitochondrial DNA (mtDNA) and routine genomic DNA analysis were concordant in 52/73 (71 %) patients. We conclude that D310 mutation status might aid in determining clonality of clinically challenging synchronous or metachronous tumors. To this end, next generation sequencing targeted genomic DNA assays should be complemented with mtDNA markers, such as the D310 repeat. PMID- 26276354 TI - Octreotide LAR and tamoxifen versus tamoxifen in phase III randomize early breast cancer trials: NCIC CTG MA.14 and NSABP B-29. AB - NCIC CTG MA.14 and NSABP B-29 trials examined the addition of Octreotide LAR (OCT) to 5 years of tamoxifen (TAM). Gallbladder toxicity led to B-29 discontinuation of OCT, and MA.14 OCT administration shortened to 2 years. Median follow-up was 9.8 years for 667 MA.14 patients and 6.8 years for 893 B-29 patients. The primary endpoint was disease-free survival (DFS), defined as time from randomization to time of breast cancer recurrence; second primary cancer other than squamous or basal cell skin carcinoma, cervical carcinoma in situ, or lobular breast carcinoma in situ; or death. The primary statistical test was a univariable pooled stratified log-rank test; multivariable assessment was with Cox regression. For MA.14, 97% of patients were >=50 years; for B-29, 62%. MA.14 patients were 53% lymph node negative (LN-) while B-29 were 100% LN-; 33% of MA.14 patients received adjuvant chemotherapy, 2% concurrently, while B-29 had 53% concurrent chemotherapy. MA.14 patients were 90% hormone receptor positive; B 29, 100%. MA.14 patients experienced 5-year DFS of 80% with TAM, 76% with TAM + OCT; B-29 patients had 5-year DFS of 88% for both arms. Pooled univariable TAM + OCT to TAM hazard ratio (HR) was 0.99 (95% CI 0.81-1.20; p = 0.69): for MA.14, HR = 0.94 (0.73-1.20; p = 0.50); for B-29, HR = 1.09 (0.80-1.50; p = 0.59). Multivariable pooled HR = 0.98 (0.81-1.20; p = 0.84). Older patients (p < 0.001), with higher T stage (p < 0.001), and LN + (p < 0.001) had shorter DFS. Addition of OCT to TAM did not significantly improve DFS; gallbladder toxicity shortened the additional administration of OCT. This does not negate targeting the insulin IGF-I receptor family with less toxic therapeutics. PMID- 26276355 TI - Mechanisms of cadmium-caused eye hypoplasia and hypopigmentation in zebrafish embryos. AB - Cadmium-caused head and eye hypoplasia and hypopigmentation has been recognized for a long time, but knowledge of the underlying mechanisms is limited. In this study, we found that high mortality occurred in exposed embryos after 24 hpf, when cadmium (Cd) dosage was above 17.8 MUM. Using high-throughput in situ hybridization screening, we found that genes labelling the neural crest and its derivative pigment cells exhibited obviously reduced expression in Cd-exposed embryos from 24 hpf, 2 days earlier than head and eye hypoplasia and hypopigmentation occurred. Moreover, based on expression of crestin, a neural crest marker, we found that embryos before the gastrula stage were more sensitive to cadmium toxicity and that damage caused by Cd on embryogenesis was dosage dependent. In addition, by phenotype observation and detection of neural crest and pigment cell markers, we found that BIO and retinoic acid (RA) could neutralize the toxic effects of Cd on zebrafish embryogenesis. In this study, we first determined that Cd blocked the formation of the neural crest and inhibited specification of pigment cells, which might contribute to the molecular mechanisms underlying the phenotype defects of head and eye hypoplasia and hypopigmentation in Cd-exposed embryos. Moreover, we found that compounds BIO or RA could neutralize the toxic effects of Cd. PMID- 26276356 TI - Effects of cadmium exposure on critical temperatures of aerobic metabolism in eastern oysters Crassostrea virginica (Gmelin, 1791). AB - Cadmium (Cd) and elevated temperatures are common stressors in estuarine and coastal environments. Elevated temperature can sensitize estuarine organisms to the toxicity of metals such as Cd and vice versa, but the physiological mechanisms of temperature-Cd interactions are not well understood. We tested a hypothesis that interactive effects of elevated temperature and Cd stress involve Cd-induced reduction of the aerobic scope of an organism thereby narrowing the thermal tolerance window of oysters. We determined the effects of prolonged Cd exposure (50 MUg Cd l(-1)for 30 days) on the upper critical temperature of aerobic metabolism (assessed by accumulation of anaerobic end products L-alanine, succinate and acetate), cellular energy status (assessed by the tissue levels of adenylates, phosphagen/aphosphagen and glycogen and lipid reserves) and oxidative damage during acute temperature rise (20-36 degrees C) in the eastern oysters Crassostrea virginica. The upper critical temperature (TcII) was shifted to lower values (from 28 to 24 degrees C) in Cd-exposed oysters in spring and was lower in both control and Cd-exposed groups in winter (24 and <20 degrees C, respectively). This indicates a reduction of thermal tolerance of Cd-exposed oysters associated with a decrease of the aerobic scope of the organism and early transition to partial anaerobiosis. Acute warming had no negative effects on tissue energy reserves or parameters of cellular energy status of oysters (except a decrease in adenylate content at the extreme temperature of 36 degrees C) but led to an increase in oxidative lesions of proteins at extreme temperatures. These data show that transition to partial anaerobiosis (indicated by the accumulation of anaerobic end products) is the most sensitive biomarker of temperature-induced transition to energetically non-sustainable state in oysters, whereas disturbances in the cellular energy status (i.e. decline in adenylate and phosphagen levels) and oxidative stress ensue at considerably higher temperatures, nearing the lethal range. This study indicates that long-term exposure of oysters to environmentally relevant levels of Cd may increase their sensitivity to elevated temperatures during seasonal warming and/or the global climate change in polluted estuaries. PMID- 26276357 TI - Gab1 regulates SDF-1-induced progression via inhibition of apoptosis pathway induced by PI3K/AKT/Bcl-2/BAX pathway in human chondrosarcoma. AB - In recent decades, the stromal cell-derived factor-l (SDF-1) and Gab1 have been investigated to be involved in oncogenesis. However, it is scarcely reported that SDF-1-Gab1 pathway mediates proliferation and apoptosis in human chondrosarcoma (CS). In this study, we assessed the expression of Gab1 in 90 CS solid tumors by immunohistochemistry, immunoblotting, and qRT-PCR, and then, some in vitro assays were also applied to CS cells treated with SDF-1. We observed that the overexpression of Gab1 was positively correlated with lung metastasis and recurrence, and acts as an independent prognostic factor for CS patients. Gab1 expression was up-regulated in response to SDF-1 stimulation in CS cell line JJ012, SW1353, L3252. Overexpression of Gab1 increased Bcl-2/BAX ratio to promote cell growth via PI3K/AKT. On the other hand, silencing of Gab1 accelerated apoptosis and repressed the growth of CS cells, which further caused the inhibition of G1/S phase transition and decreased invasion capacity in CS cell lines. In vivo assay identified that the knockdown of Gab1 interfered with the tumor mass formation. In conclusion, our data identified overexpression of Gab1 in CS tissues, and Gab1 can be recommended as a novel biomarker for diagnosis and prognosis in patients with CS. Additionally, PI3K/AKT/Bcl-2/BAX axis was involved in Gab1-induced CS progression, indicating Gab1 might act as a new target for the treatment of CS patients. PMID- 26276358 TI - LRRC3B is downregulated in non-small-cell lung cancer and inhibits cancer cell proliferation and invasion. AB - LRRC3B has emerged as a tumor suppressor in several human cancers. However, its expression pattern and biological roles in human non-small-cell lung cancer (NSCLC) have not been explored. In the present study, we investigated clinical significance of LRRC3B in 101 NSCLC specimens. We found that LRRC3B expression was downregulated in NSCLC tissues compared with normal bronchial epithelium and that its downregulation significantly correlated with tumor-node-metastasis (TNM) stage (p < 0.0001), nodal metastasis (p < 0.0001), and poor patient prognosis (p = 0.0016, log-rank test). We also checked LRRC3B levels in several lung cancer cell lines and found that its expression was downregulated in four of nine lung cancer cell lines compared with normal human bronchial epithelial (NHBE) cell line. We further explored the biological role of LRRC3B. LRRC3B plasmid transfection in H460 and A549 cell lines inhibited proliferation, colony formation ability, and invading ability. Furthermore, we identified that LRRC3B could inhibit cell cycle progression with downregulation of cyclin D1 and decreased MMP9 expression. In addition, LRRC3B depletion in HBE cells promoted proliferation and invasion. In conclusion, our data suggested that LRRC3B may serve as an important tumor suppressor in NSCLC. PMID- 26276359 TI - Association of GRM4 gene polymorphisms with susceptibility and clinicopathological characteristics of osteosarcoma in Guangxi Chinese population. AB - Osteosarcoma is the most frequent malignant primary bone tumor. GRM4 is expressed in human osteosarcoma cells, and high expression of mGluR4 in osteosarcoma tissues is related to poor prognosis. The aim of this study was to investigate the association between polymorphism of the GRM4 gene and the susceptibility to osteosarcoma in a Chinese population. In a case-control study, we investigated polymorphisms in the GRM4 gene (rs2229901, rs733457, and rs1906953) with a real time quantitative polymerase chain reaction (PCR) assay (TaqMan). The study was conducted with 126 Chinese patients with osteosarcoma and 168 Chinese subjects in a control group. Unconditional logistic regression was used to analyze the correlation between single nucleotide polymorphisms (SNPs) and osteosarcoma risk. Different survival rates of different genotypic patients with osteosarcoma were analyzed through Kaplan-Meier. There were statistically significant differences in the distributions of the rs1906953 genotypes between the cases and control group (P = 0.034). However, there was no remarkable difference in the three genotypes of GRM4 gene rs2229901 locus between the patient group and control group (P = 0.369). Survival analysis for rs1906953 showed that the median survival time of osteosarcoma patients with the CC genotype was significantly shorter compared to the CT and TT genotypes; patients carrying CC genotype have apparently got a decrease in their recurrence-free survival time in comparison with patients carrying TT genotype. Our data suggest that GRM4 gene polymorphism is closely related to the morbidity and metastasis of osteosarcoma in a Chinese population. PMID- 26276360 TI - Risk factors for skeletal-related events (SREs) and factors affecting SRE-free survival for nonsmall cell lung cancer patients with bone metastases. AB - Skeletal-related events (SREs) for nonsmall cell lung cancer (NSCLC) patients with bone metastasis lead to serious morbidity. The aim of this study was to determine risk factors for SREs in NSCLC patients with bone metastasis and the factors influencing SRE-free survival and overall survival (OS). From 2000 to 2012, we evaluated retrospectively 835 NSCLC patients. Three hundred and thirty five of them with bone metastasis were included in the study. SREs and the other prognostic factors were evaluated by univariate and multivariate analysis for SRE free survival and OS. SREs were detected in 244 patients (72.8 %). The most common SREs were the need for radiotherapy (43.2 %) and malignant hypercalcemia (17.6 %). The median time to first SRE was 3.5 months at the median follow-up of 17 months. A multivariate analysis showed that the presence of bone metastasis at diagnosis (p < 0.001), the number of bone metastasis (p = 0.001), baseline hypercalcemia (p = 0.004), and the presence of palliative radiotherapy (p = 0.04) were independent prognostic factors for SRE-free survival. A logistic regression analysis identified that the presence of bone metastasis at diagnosis [odds ratio (OR), 12.6], number of bone metastasis (OR, 3.05), and baseline hypercalcemia (OR, 0.33) were found to be predictive factors in the developing of SRE. The median OS time for patients with SRE was worse than that for patients without SRE (7 vs 12 months, respectively). For OS, male gender, ECOG performance status (PS), high lactate dehydrogenase (LDH) level, hypoalbuminemia, the presence of bone metastasis at diagnosis, the number of bone metastasis, the presence of SREs, the presence of bisphosphonate therapy, and palliative radiotherapy were independent prognostic indicators for OS by the multivariate analysis. Our results indicated that the frequency of SREs was high and the presence of bone metastasis at the time of diagnosis, baseline hypercalcemia, and multiple bone metastases were significant factors predicting the occurrence of SREs. If bone metastases diagnose earlier, treatments for the prevention of SREs may be initiated earlier; thus, the deterioration of quality of life may be preserved. PMID- 26276361 TI - Downregulated ECRG4 is associated with poor prognosis in renal cell cancer and is regulated by promoter DNA methylation. AB - Esophageal cancer-related gene 4 (ECRG4) has been proposed as a putative tumor suppressor gene in several tumors. However, the role and regulation of ECRG4 in the pathogenesis of human renal cancer remain largely unknown. Our current study revealed that expression of ECRG4 is downregulated in renal cell lines and renal cancer tissues. ECRG4 expression was significantly associated with histological grade of tumors (p < 0.001), primary tumor stage (p = 0.017), and distant metastasis (p = 0.017). Low expression of ECRG4 was an independent prognostic indicator for survival of renal cancer patients. Silencing of ECRG4 expression in renal cell lines was associated with its promoter methylation. Moreover, ectopic expression of ECRG4 markedly inhibited cell proliferation and invasion in renal cancer cell lines. These results indicated that ECRG4 is frequently silenced by the methylation of promoter in renal cell cancers. ECRG4 may be a tumor suppressor in renal cancer and serve as a prognostic marker. PMID- 26276362 TI - Measurement of physical activity in older adult interventions: a systematic review. AB - BACKGROUND: Interventions to promote physical activity (PA) among older adults can positively impact PA behaviour and other health outcomes. Measurement of PA must be valid and reliable; however, the degree to which studies employ valid and reliable measures of PA is unclear. The purpose of this systematic review was to evaluate the measurement tools used in interventions to increase PA among older adults (65+ years), including both self-report measures and objective measures. In addition, the implications of these different measurement tools on study results were evaluated and discussed. METHODS: Four electronic research databases (MEDLINE, PsychINFO, Web of Science and EBSCO) were used to identify published intervention studies measuring the PA behaviour of adults over 65 years of age. Studies were eligible if: (1) PA was an outcome; (2) there was a comparison group and (3) the manuscript was published in English. Data describing measurement methods and properties were extracted and reviewed. RESULTS: Of the 44 studies included in this systematic review, 32 used self-report measures, 9 used objective measures and 3 used both measures. 29% of studies used a PA measure that had neither established validity nor reliability, and only 63% of measures in the interventions had established both validity and reliability. Only 57% of measures had population-specific reliability and 66% had population-specific validity. CONCLUSIONS: A majority of intervention studies to help increase older adult PA used self-report measures, even though many have little evidence of validity and reliability. We recommend that future researchers utilise valid and reliable measures of PA with well-established evidence of psychometric properties such as hip-accelerometers and the Community Health Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults. PMID- 26276363 TI - Perceived Job Stress and Presence of Hypertension Among Administrative Officers in Sri Lanka. AB - A cross-sectional survey was carried out among 275 and 760 randomly selected senior officers (SOs) and managerial assistants (MAs) aged between 30 and 60 years. Sum of scores of efforts, rewards, and overcommitment and effort-reward ratio assessed job stress. Blood pressure was measured and classified using JNC-7 guidelines. The response rates of SOs and MAs were 98.9% and 97.2%, respectively. The prevalence of job stress based on high effort-rewards imbalance among SOs and MAs was 74.6% and 80.5%, respectively. The prevalence of overcommitment among SOs and MAs was 35.3% and 29%, respectively. Statistically significant differences (P = .05) were observed between the prevalence of effort-reward imbalance and overcommitment among SOs and MAs. Multivariate analysis indicated effort-reward imbalance (odds ratio [OR] = 2.8; 95% confidence interval [CI] = 1.1-7.4), high efforts (OR = 2.5; 95% CI = 1.2-5.3), and overcommitment (OR = 2.5; 95% CI = 1.1 5.6) were significantly associated with hypertension among SOs. Similarly, effort reward imbalance and high efforts increased the risk of hypertension by 2-fold (OR = 2.2; 95% CI = 1.1-4.2) and 3-fold (OR = 3.02; 95% CI = 1.9-4.8), respectively, among the MAs. A significant number of administrators are afflicted by job stress, and job stress was significantly associated with hypertension. PMID- 26276364 TI - Level of Physical Activity in Population Aged 16 to 65 Years in Rural Kerala, India. AB - Kerala is a state in India with a high prevalence of cardiovascular diseases and diabetes. In order to control these diseases, the prevalence of modifiable risk factors such as low physical activity need to be studied. For this a cross sectional study was conducted to assess the level of physical activity among 240 residents aged between 15 and 65 years in Kulappuram, a village in north Kerala. Low level of physical activity was seen in 65.8% of the study participants. The average duration of moderate to vigorous intensity physical activity per day in different domains such as work, travel, and recreation were 40.5, 10.1, and 12.7 minutes, respectively. The average duration of sedentary activities was 284.3 minutes per day. The level of physical activity was more among those engaged in unskilled work (adjusted odds ratio = 4.32; confidence interval = 1.38-13.51) and unmarried persons (adjusted odds ratio = 3.65; confidence interval = 1.25-10.65). No statistically significant difference in physical activity level was seen in different age, education, religious, and economic categories. The study concludes that the physical activity level was low in the study population. PMID- 26276365 TI - Sustained Attention in Auditory and Visual Monitoring Tasks: Evaluation of the Administration of a Rest Break or Exogenous Vibrotactile Signals. AB - OBJECTIVE: Performance and mental workload were observed for the administration of a rest break or exogenous vibrotactile signals in auditory and visual monitoring tasks. BACKGROUND: Sustained attention is mentally demanding. Techniques are required to improve observer performance in vigilance tasks. METHOD: Participants (N = 150) monitored an auditory or a visual display for changes in signal duration in a 40-min watch. During the watch, participants were administered a rest break or exogenous vibrotactile signals. RESULTS: Detection accuracy was significantly greater in the auditory than in the visual modality. A short rest break restored detection accuracy in both sensory modalities following deterioration in performance. Participants experienced significantly lower mental workload when monitoring auditory than visual signals, and a rest break significantly reduced mental workload in both sensory modalities. Exogenous vibrotactile signals had no beneficial effects on performance, or mental workload. CONCLUSION: A rest break can restore performance in auditory and visual vigilance tasks. Although sensory differences in vigilance tasks have been studied, this study is the initial effort to investigate the effects of a rest break countermeasure in both auditory and visual vigilance tasks, and it is also the initial effort to explore the effects of the intervention of a rest break on the perceived mental workload of auditory and visual vigilance tasks. Further research is warranted to determine exact characteristics of effective exogenous vibrotactile signals in vigilance tasks. APPLICATION: Potential applications of this research include procedures for decreasing the temporal decline in observer performance and the high mental workload imposed by vigilance tasks. PMID- 26276367 TI - Extinction of chained instrumental behaviors: Effects of consumption extinction on procurement responding. AB - Operant behavior is typically organized into sequences of responses that eventually lead to a reinforcer. Response elements can be categorized as those that directly lead to reward consumption (i.e., a consumption response) and those that lead to the opportunity to make the consumption response (i.e., a procurement response). These responses often differ topographically and in terms of the discriminative stimuli that set the occasion for them. We have recently shown that extinction of the procurement response acts to weaken the specific associated consumption response, and that active inhibition of the procurement response is required for this effect. To expand the analysis of the associative structure of chains, in the present experiments we asked the reverse question: whether extinction of consumption behavior results in a decrease in the associated procurement response in a discriminated heterogeneous chain. In Experiment 1, extinction of consumption alone led to an attenuation of the associated procurement response only when rats were allowed to make the consumption response in extinction. Exposure to the consumption stimulus alone was not sufficient to produce weakened procurement responding. In Experiment 2, rats learned two distinct heterogeneous chains, and extinction of one consumption response specifically weakened the procurement response associated with it. The results add to the evidence suggesting that rats learn a highly specific associative structure in behavior chains, emphasizing the role of learning response inhibition in extinction. PMID- 26276366 TI - The standard diagnosis, treatment, and follow-up of gastrointestinal stromal tumors based on guidelines. AB - Although gastrointestinal stromal tumors (GISTs) are a rare type of cancer, they are the commonest sarcoma in the gastrointestinal tract. Molecularly targeted therapy, such as imatinib therapy, has revolutionized the treatment of advanced GIST and facilitates scientific research on GIST. Nevertheless, surgery remains a mainstay of treatment to obtain a permanent cure for GIST even in the era of targeted therapy. Many GIST guidelines have been published to guide the diagnosis and treatment of the disease. We review current versions of GIST guidelines published by the National Comprehensive Cancer Network, by the European Society for Medical Oncology, and in Japan. All clinical practice guidelines for GIST include recommendations based on evidence as well as on expert consensus. Most of the content is very similar, as represented by the following examples: GIST is a heterogeneous disease that may have mutations in KIT, PDGFRA, HRAS, NRAS, BRAF, NF1, or the succinate dehydrogenase complex, and these subsets of tumors have several distinctive features. Although there are some minor differences among the guidelines--for example, in the dose of imatinib recommended for exon 9-mutated GIST or the efficacy of antigen retrieval via immunohistochemistry--their common objectives regarding diagnosis and treatment are not only to improve the diagnosis of GIST and the prognosis of patients but also to control medical costs. This review describes the current standard diagnosis, treatment, and follow-up of GISTs based on the recommendations of several guidelines and expert consensus. PMID- 26276368 TI - How New Caledonian crows solve novel foraging problems and what it means for cumulative culture. AB - New Caledonian crows make and use tools, and tool types vary over geographic landscapes. Social learning may explain the variation in tool design, but it is unknown to what degree social learning accounts for the maintenance of these designs. Indeed, little is known about the mechanisms these crows use to obtain information from others, despite the question's importance in understanding whether tool behavior is transmitted via social, genetic, or environmental means. For social transmission to account for tool-type variation, copying must utilize a mechanism that is action specific (e.g., pushing left vs. right) as well as context specific (e.g., pushing a particular object vs. any object). To determine whether crows can copy a demonstrator's actions as well as the contexts in which they occur, we conducted a diffusion experiment using a novel foraging task. We used a nontool task to eliminate any confounds introduced by individual differences in their prior tool experience. Two groups had demonstrators (trained in isolation on different options of a four-option task, including a two-action option) and one group did not. We found that crows socially learn about context: After observers see a demonstrator interact with the task, they are more likely to interact with the same parts of the task. In contrast, observers did not copy the demonstrator's specific actions. Our results suggest it is unlikely that observing tool-making behavior transmits tool types. We suggest it is possible that tool types are transmitted when crows copy the physical form of the tools they encounter. PMID- 26276369 TI - Rapid assessment of technical competency: the 8-min suture test. AB - BACKGROUND: Although simulation training and evaluation have become increasingly popular for teaching minimally invasive surgery, tools to measure open surgical skills remain underdeveloped. As there is increasing demand for objective measures of technical competency at the completion of surgical training (postgraduate year [PGY]-6 and -7), this project was designed to assess the feasibility, reliability, and validity of a novel open surgical skills evaluation tool, the 8-min suture test (8MST). METHODS: During an annual surgical skills laboratory session, fellows and residents were asked to complete a simulated end to-end vascular anastomosis. They were limited to 8 min to perform the anastomosis between two 12-mm Dacron grafts mounted on a customized platform. Their real-time and video-recorded performance was scored by two blinded evaluators and compared with their faculty-rated technical performance on clinical rotations completed around the time of 8MST administration. RESULTS: PGY 6 and PGY-7 trainees were compared across several domains including 8MST total score (4.6 versus 5.5, P = 0.030), 8MST setup score (2.3 versus 2.4, P = 0.797), 8MST technical score (2.3 versus 3.1, P = 0.026), and clinical performance score (3.1 versus 3.6, P = 0.006). Comparison of 8MST total score to the clinical performance score identified a strong relationship with a Pearson r = 0.55 (P < 0.001) and r(2) = 0.30. Additionally, 8MST displayed high inter-rater reliability and test-retest reliability. CONCLUSIONS: The 8MST is a rapid, feasible, inexpensive, reliable, and valid test for assessment of surgical trainee technical abilities. PMID- 26276370 TI - PTH and Vitamin D Repress DMP1 in Cementoblasts. AB - A complex feedback mechanism between parathyroid hormone (PTH), 1,25(OH)2D3 (1,25D), and fibroblast growth factor 23 (FGF-23) maintains mineral homeostasis, in part by regulating calcium and phosphate absorption/reabsorption. Previously, we showed that 1,25D regulates mineral homeostasis by repressing dentin matrix protein 1 (DMP1) via the vitamin D receptor pathway. Similar to 1,25D, PTH may modulate DMP1, but the underlying mechanism remains unknown. Immortalized murine cementoblasts (OCCM.30), similar to osteoblasts and known to express DMP1, were treated with PTH (1-34). Real-time quantitative polymerase chain reaction (PCR) and Western blot revealed that PTH decreased DMP1 gene transcription (85%) and protein expression (30%), respectively. PTH mediated the downregulation of DMP1 via the cAMP/protein kinase A (PKA) pathway. Immunohistochemistry confirmed the decreased localization of DMP1 in vivo in cellular cementum and alveolar bone of mice treated with a single dose (50 ug/kg) of PTH (1-34). RNA-seq was employed to further identify patterns of gene expression shared by PTH and 1,25D in regulating DMP1, as well as other factors involved in mineral homeostasis. PTH and 1,25D mutually upregulated 36 genes and mutually downregulated 27 genes by >=2-fold expression (P <= 0.05). Many identified genes were linked with the regulation of bone/tooth homeostasis, cell growth and differentiation, calcium signaling, and DMP1 transcription. Validation of RNA-seq results via PCR array confirmed a similar gene expression pattern in response to PTH and 1,25D treatment. Collectively, these results suggest that PTH and 1,25D share complementary effects in maintaining mineral homeostasis by mutual regulation of genes/proteins associated with calcium and phosphate metabolism while also exerting distinct roles on factors modulating mineral metabolism. Furthermore, PTH may modulate phosphate homeostasis by downregulating DMP1 expression via the cAMP/PKA pathway. Targeting genes/proteins mutually governed by PTH and 1,25D may be a viable approach for designing new therapies for preserving mineralized tissue health. PMID- 26276371 TI - Enhanced Dentinogenesis of Pulp Progenitors by Early Exposure to FGF2. AB - Members of the fibroblast growth factor (FGF) family play essential and important roles in primary and reparative dentinogenesis. Although there appears to be a general agreement on the effects of FGF signaling on the proliferation of pulp cells, there are conflicting results regarding its effects on odontoblast differentiation. We recently examined the effects of continuous exposure of dental pulp cells to FGF2 and showed that the effects of FGF2 on differentiation of progenitor cells into odontoblasts were stage specific and dependent on the stage of cell maturity. The purpose of this study was to gain further insight into cellular and molecular mechanisms regulating the stimulatory effects of FGF2 on odontoblast differentiation. To do so, we examined the effects of early and limited exposure of pulp cells from a series of green fluorescent protein (GFP) reporter transgenic mice that display stage-specific activation of transgenes during odontoblast differentiation to FGF2. Our results showed that early and limited exposure of pulp cells to FGF2 did not have significant effects on the extent of mineralization but induced significant increases in the expression of Dmp1 and Dspp and the number of DMP1-GFP(+) and DSPP-Cerulean(+) odontoblasts. Our results also showed that the stimulatory effects of FGF2 on odontoblast differentiation were mediated through FGFR/MEK/Erk1/2 signaling, increases in Bmp2, and activation of the BMP/BMPR signaling pathway. These observations show that early and limited exposure of pulp cells to FGF2 alone promotes odontoblast differentiation and provides critical insight for applications of FGF2 in dentin regeneration. PMID- 26276372 TI - Photocurable, Antimicrobial Quaternary Ammonium-modified Nanosilica. AB - In this study, novel, quaternary ammonium methacrylate-modified silica nanoparticles (QMSNs) were synthesized for the first time and proposed as possible antimicrobial particles for free-radical, photocurable monomers. Such monomers have the potential to polymerize with other methacrylate monomers and create antimicrobial polymers. The silica nanoparticles were modified by quaternary ammonium methacrylate functionality and incorporated at 0 to 10 wt% into a 1:1 (by mass) bisphenol A glycerolate dimethacrylate (BisGMA)/triethylene glycol dimethacrylate (TEGDMA) resin. Thermal stability of the pristine and modified silica nanoparticles was examined by thermogravimetric analyses. Atomic force microscopy was used to investigate the size distribution and topography of the nanoparticles. For evaluation of the mechanical properties of the samples, flexural strength was measured using a 3-point bending test method. The flexural strength of the composites containing QMSNs increased with increasing modified silica content. The antimicrobial activity of samples was investigated against some standard microorganisms (Streptococcus mutans, Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans), and then cytotoxicity and viability were quantified. Incorporation of 2.5% to 10% (by mass) QMSNs into BisGMA/TEGDMA demonstrated antimicrobial activity, but >=5 wt% significantly reduced cell viability. PMID- 26276373 TI - Feasibility of a Website and a Hospital-Based Online Portal for Young Adults With Juvenile Idiopathic Arthritis: Views and Experiences of Patients. AB - BACKGROUND: To improve knowledge and to encourage active involvement of young adults with juvenile idiopathic arthritis (JIA), an informative website with written and video information and an online portal with access to the personal medical record, self-monitoring, and e-consult functionalities were developed. Before implementing these applications in daily practice, it is important to gain insight into their feasibility in terms of ease of use, perceived usefulness and intention to use. OBJECTIVE: The aim of this study was to evaluate and to examine the feasibility of the website and the online portal for young adults with JIA. METHODS: A qualitative, feasibility study was conducted among the first users: 13 young adults with JIA. After provided access to the website and online portal, patients were interviewed on perceived usefulness, ease of use, and intention to (re)use the applications. RESULTS: Participants in the study considered the website and online portal as useful and easy-to-use. New medical information and feedback would motivate them to revisit the applications again. On the website, videos showing other young adults, telling how they handle their condition, were found as the most useful. On the portal, access to their medical records was most appreciated: it made the young JIA patients feel in control and it helped them monitor symptoms and disease activity. e-consults were thought to facilitate communication with physicians. CONCLUSIONS: The young adults considered both the website and the online portal as feasible, but they also had valuable suggestions to improve accessibility and use. Based on these findings, a news and event section was added on the website and a direct link was made to a discussion board and social media. To provide and support health information, the website is actively used in daily care. Considering the online portal, the use of self monitoring tools and e-consult can be stimulated if there is direct linkage to treatment and feedback from the multidisciplinary team. Feasibility testing, before implementing the website and online portal in daily practice, has proven to be a valuable step. Results led to improvements in terms of integration into standard care and topics for further research. PMID- 26276375 TI - Recombinant human interleukin-11 (IL-11) is a protective factor in severe sepsis with thrombocytopenia: A case-control study. AB - OBJECTIVE: To examine the platelet recovering and anti-inflammatory effects of IL 11 in the treatment of sepsis, accompanied with thrombocytopenia and to investigate the associated mechanisms via a case-control study. METHODS: 105 patients enrolled for the study were segregated into (1) IL-11 therapy group and (2) conventional therapy group. The IL-11 therapy group was given additional recombinant human IL-11 treatment. Laboratory examinations of IL-11, IL-6, TNF alpha, PT, APTT, WBC, PLT counts in blood routine assays and PCT, CRP and APACHE II scores were performed and the results were recorded. RESULTS: The PLT counts in the IL-11 therapy group were higher than those in the conventional therapy group. No obvious difference in WBC counts or CRP levels was observed between the two groups. The highest levels of TNF-alpha were observed on day 3 in the conventional therapy group while it was observed on day 1 in the IL-11 therapy group, both of which subsequently declined gradually. The level of IL-6 was significantly lower in the IL-11 therapy group from 3 to 14 days, while there was a gradual elevation of IL-11. IL-11 therapy downregulated the expression of the sepsis indicator PCT and reduced the APACHE II score from 3 to 14 days. The conventional therapy group had a significantly higher mortality rate within 28 days. CONCLUSION: IL-11 has a protective role and can accelerate recovery of platelets, and remarkably lessen the extent of inflammatory responses, hence reducing the mortality in sepsis patients accompanied with thrombocytopenia. PMID- 26276376 TI - Role of aetiology, diabetes, tobacco smoking and hypertension in hepatocellular carcinoma survival. AB - BACKGROUND: Aim of this study was to investigate the role of aetiology, diabetes, tobacco smoking and hypertension in the survival of patients with hepatocellular carcinoma. METHODS: A prospective cohort of 552 patients (81.5% males, mean age 64.4 years) first diagnosed with hepatocellular carcinoma in 1995-2001 in Brescia, Italy, was retrospectively analyzed. Data on the presence of diabetes mellitus, hypertension, heavy alcohol intake and tobacco smoking were obtained from patients' clinical charts or interviews. Survival analysis was performed using univariate and multivariate methods (Cox proportional hazards model). RESULTS: 33% had a history of heavy alcohol intake, 24.3% had viral hepatitis and 33.5% had both aetiologies. Diabetes, hypertension and tobacco smoking were found in 29.9%, 37.9% and 35.9%, respectively. During follow-up (median 19.9 months), the median survival was 19.9 (95% confidence interval [CI] 16.7-22.8) months. Using multivariate Cox regression models, alcohol-related liver disease and diabetes were found to be associated with mortality, with hazard ratios of 1.32 (95% CI 0.99-1.75) and 1.25 (95% CI 1.02-1.54), respectively. Hypertension and smoking habit did not influence survival. CONCLUSIONS: Alcohol aetiology and the presence of diabetes were positively associated with patient mortality with hepatocellular carcinoma, whereas tobacco smoking and hypertension were not. PMID- 26276374 TI - Beyond Candida albicans: Mechanisms of immunity to non-albicans Candida species. AB - The fungal genus Candida encompasses numerous species that inhabit a variety of hosts, either as commensal microbes and/or pathogens. Candida species are a major cause of fungal infections, yet to date there are no vaccines against Candida or indeed any other fungal pathogen. Our knowledge of immunity to Candida mainly comes from studies on Candida albicans, the most frequent species associated with disease. However, non-albicans Candida (NAC) species also cause disease and their prevalence is increasing. Although research into immunity to NAC species is still at an early stage, it is becoming apparent that immunity to C. albicans differs in important ways from non-albicans species, with important implications for treatment, therapy and predicted demographic susceptibility. This review will discuss the current understanding of immunity to NAC species in the context of immunity to C. albicans, and highlight as-yet unanswered questions. PMID- 26276377 TI - Early prediction of long-term upper limb spasticity after stroke: part of the SALGOT study. AB - OBJECTIVE: To identify predictors and the optimal time point for the early prediction of the presence and severity of spasticity in the upper limb 12 months poststroke. METHODS: In total, 117 patients in the Gothenburg area who had experienced a stroke for the first time and with documented arm paresis day 3 poststroke were consecutively included. Assessments were made at admission and at 3 and 10 days, 4 weeks, and 12 months poststroke. Upper limb spasticity in elbow flexion/extension and wrist flexion/extension was assessed with the modified Ashworth Scale (MAS). Any spasticity was regarded as MAS >=1, and severe spasticity was regarded as MAS >=2 in any of the muscles. Sensorimotor function, sensation, pain, and joint range of motion in the upper limb were assessed with the Fugl-Meyer assessment scale, and, together with demographic and diagnostic information, were included in both univariate and multivariate logistic regression analysis models. Seventy-six patients were included in the logistic regression analysis. RESULTS: Sensorimotor function was the most important predictor both for any and severe spasticity 12 months poststroke. In addition, spasticity 4 weeks poststroke was a significant predictor for severe spasticity. The best prediction model for any spasticity was observed 10 days poststroke (85% sensitivity, 90% specificity). The best prediction model for severe spasticity was observed 4 weeks poststroke (91% sensitivity, 92% specificity). CONCLUSIONS: Reduced sensorimotor function was the most important predictor both for any and severe spasticity, and spasticity could be predicted with high sensitivity and specificity 10 days poststroke. PMID- 26276378 TI - Comment: How and why to predict spasticity after stroke? PMID- 26276379 TI - Watch your neighbor's garden, or Delphi's oracle for unruptured intracranial aneurysm treatment. PMID- 26276381 TI - Using Targeted Resequencing for Identification of Candidate Genes and SNPs for a QTL Affecting the pH Value of Chicken Meat. AB - Using targeted genetical genomics, a quantitative trait locus (QTL) affecting the initial postmortem pH value of chicken breast muscle (Pectoralis major) on chromosome 1 (GGA1) recently was fine-mapped. Thirteen genes were present in the QTL region of approximately 1 Mb. In this study, 10 birds that were inferred to be homozygous for either the high (QQ) or low (qq) QTL allele were selected for resequencing. After enrichment for 1 Mb around the QTL region, >500 * coverage for the QTL region in each of the 10 birds was obtained. In total 5056 single nucleotide polymorphisms (SNPs) were identified for which the genotypes were consistent with one of the QTL genotypes. We used custom tools to identify putative causal mutations in the mapped QTL region from these SNPs. Four nonsynonymous SNPs differentiating the two QTL genotype groups were identified within four local genes (PRDX4, EIF2S3, PCYT1B, and E1BTD2). Although these are likely candidate SNPs to explain the QTL effect, 54 additional consensus SNPs were detected within gene-related regions (untranslated regions, splicing sites CpG island, and promoter regions) for the QQ birds and 71 for the qq birds. These could also play a role explaining the observed QTL effect. The results provide an important step for prioritizing among a large amount of candidate mutations and significantly contribute to the understanding of the genetic mechanisms affecting the initial postmortem pH value of chicken muscle. PMID- 26276380 TI - The unruptured intracranial aneurysm treatment score: a multidisciplinary consensus. AB - OBJECTIVE: We endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research. METHODS: An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39 panel members involved in identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (vr*) (vr* = 0 indicating excellent agreement and vr* = 1 indicating poor agreement). RESULTS: The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1-4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1-4.4) for panel members and 4.5 (95% CI 4.3-4.6) for external reviewers (p = 0.017). Mean Likert scores were 4.2 (95% CI 4.1-4.3) for interventional reviewers (n = 56) and 4.1 (95% CI 3.9-4.4) for noninterventional reviewers (n = 12) (p = 0.290). Overall IRA (vr*) for both cohorts was 0.026 (95% CI 0.019-0.033). CONCLUSIONS: This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA. PMID- 26276382 TI - Developmental Transcriptome for a Facultatively Eusocial Bee, Megalopta genalis. AB - Transcriptomes provide excellent foundational resources for mechanistic and evolutionary analyses of complex traits. We present a developmental transcriptome for the facultatively eusocial bee Megalopta genalis, which represents a potential transition point in the evolution of eusociality. A de novo transcriptome assembly of Megalopta genalis was generated using paired-end Illumina sequencing and the Trinity assembler. Males and females of all life stages were aligned to this transcriptome for analysis of gene expression profiles throughout development. Gene Ontology analysis indicates that stage specific genes are involved in ion transport, cell-cell signaling, and metabolism. A number of distinct biological processes are upregulated in each life stage, and transitions between life stages involve shifts in dominant functional processes, including shifts from transcriptional regulation in embryos to metabolism in larvae, and increased lipid metabolism in adults. We expect that this transcriptome will provide a useful resource for future analyses to better understand the molecular basis of the evolution of eusociality and, more generally, phenotypic plasticity. PMID- 26276383 TI - Ensemble Learning of QTL Models Improves Prediction of Complex Traits. AB - Quantitative trait locus (QTL) models can provide useful insights into trait genetic architecture because of their straightforward interpretability but are less useful for genetic prediction because of the difficulty in including the effects of numerous small effect loci without overfitting. Tight linkage between markers introduces near collinearity among marker genotypes, complicating the detection of QTL and estimation of QTL effects in linkage mapping, and this problem is exacerbated by very high density linkage maps. Here we developed a thinning and aggregating (TAGGING) method as a new ensemble learning approach to QTL mapping. TAGGING reduces collinearity problems by thinning dense linkage maps, maintains aspects of marker selection that characterize standard QTL mapping, and by ensembling, incorporates information from many more markers-trait associations than traditional QTL mapping. The objective of TAGGING was to improve prediction power compared with QTL mapping while also providing more specific insights into genetic architecture than genome-wide prediction models. TAGGING was compared with standard QTL mapping using cross validation of empirical data from the maize (Zea mays L.) nested association mapping population. TAGGING-assisted QTL mapping substantially improved prediction ability for both biparental and multifamily populations by reducing both the variance and bias in prediction. Furthermore, an ensemble model combining predictions from TAGGING-assisted QTL and infinitesimal models improved prediction abilities over the component models, indicating some complementarity between model assumptions and suggesting that some trait genetic architectures involve a mixture of a few major QTL and polygenic effects. PMID- 26276384 TI - Endoplasmic Reticulum Stress-Related Genes in Yellow Catfish Pelteobagrus fulvidraco: Molecular Characterization, Tissue Expression, and Expression Responses to Dietary Copper Deficiency and Excess. AB - Two endoplasmic reticulum (ER) molecular chaperones [glucose-regulated protein 78 (grp78) and calreticulin (crt)] and three ER stress sensors [PKR-like ER kinase (perk), inositol requiring enzyme (ire)-1alpha, and activating transcription factor (atf)-6alpha] cDNAs were first characterized from yellow catfish, Pelteobagrus fulvidraco. The predicted amino acid sequences for the yellow catfish grp78, crt, perk, ire-1alpha, and atf-6alpha revealed that the proteins contained all of the structural features that were characteristic of the five genes in other species, including the KDEL motif, signal peptide, sensor domain, and effector domain. mRNAs of the five genes mentioned above were expressed in various tissues, but their mRNA levels varied among tissues. Dietary Cu excess, but not Cu deficiency, activated the chaperones (grp78 and crt) and folding sensors in ER, and the UPR signaling pathways (i.e., perk-eif2alpha and the ire1 xbp1) in a tissue-specific manner. For the first time, our study cloned grp78, crt, perk, ire-1alpha, and atf-6alpha genes in yellow catfish and demonstrated their differential expression among tissues. Moreover, the present study also indicated differential regulation of these ER stress-related genes by dietary Cu deficiency and excess, which will be beneficial for us to evaluate effects of dietary Cu levels in fish at the molecular level, based on the upstream pathway of lipid metabolism (the ER) and thus provide novel insights regarding the nutrition of Cu in fish. PMID- 26276386 TI - Efficacy of 1 % silver sulphadiazine dressings in preventing infection of external fixation pin-tracks: a randomized study. AB - Pin-track infection (PTI) is a common complication of external fixation. Antimicrobial dressings of the pin-site interface should reduce the severity and incidence of PTI. This study is aimed at determining the efficacy of 1 % silver sulphadiazine dressings in preventing PTI in external fixation. We compared the incidence of PTI between group A (dry sterile gauze dressing) and group B (1 % silver sulphadiazine impregnated gauze dressing). PTI was diagnosed when there was: (1) redness around any pin-site, (2) tenderness near a pin-site and (3) serous or purulent discharge from the pin-skin interface. With infection, swab was obtained for microscopy, culture and sensitivity. Pin-track infections were diagnosed in 22.5 and 4.1 % of patients in groups A and B, respectively. This difference was statistically significant. The commonest organism isolated from swabs was Staphyloccus aureus. In patients with external fixation, 1 % silver sulphadiazine lowered PTI. This further underlines the need for antimicrobial dressings of pin-sites. We recommend the use of 1 % silver sulphadiazine impregnated ribbon gauze for pin-site dressings. Level of evidence II. PMID- 26276385 TI - A Flippase-Mediated GAL80/GAL4 Intersectional Resource for Dissecting Appendage Development in Drosophila. AB - Drosophila imaginal discs provide an ideal model to study processes important for cell signaling and cell specification, tissue differentiation, and cell competition during development. One challenge to understanding genetic control of cellular processes and cell interactions is the difficulty in effectively targeting a defined subset of cells in developing tissues in gene manipulation experiments. A recently developed Flippase-induced intersectional GAL80/GAL4 repression method incorporates several gene manipulation technologies in Drosophila to enable such fine-scale dissection in neural tissues. In particular, this approach brings together existing GAL4 transgenes, newly developed enhancer trap flippase transgenes, and GAL80 transgenes flanked by Flippase recognition target sites. The combination of these tools enables gene activation/repression in particular subsets of cells within a GAL4 expression pattern. Here, we expand the utility of a large collection of these enhancer-trap flippase transgenic insertion lines by characterizing their expression patterns in third larval instar imaginal discs. We screened 521 different enhancer-trap flippase lines and identified 28 that are expressed in imaginal tissues, including two transgenes that show sex-specific expression patterns. Using a line that expresses Flippase in the wing imaginal disc, we demonstrate the utility of this intersectional approach for studying development by knocking down gene expression of a key member of the planar cell polarity pathway. The results of our experiments show that these enhancer-trap flippase lines enable fine-scale manipulation in imaginal discs. PMID- 26276387 TI - Oxidized Mild Steel S235: An Efficient Anode for Electrocatalytically Initiated Water Splitting. AB - The surface of steel S235 was oxidized by Cl2 gas and checked for its electrocatalytic efficiency regarding oxygen formation in aqueous solution. If exposed to humid Cl2 gas for 110 min, steel S235 became an electrocatalyst that exhibits an overpotential for the oxygen evolution reaction (OER) of 462 mV at 1 mA cm(-2) at pH 7. The OER activity of the same sample at pH 13 was moderate (347 mV overpotential at 2.0 mA cm(-2) current density) in comparison with OER electrocatalysts developed recently. Potential versus time plots measured at a constant current demonstrate the sufficient stability of all samples under catalysis conditions at pH 7 and 13 for tens of hours. High-resolution X-ray photoelectron spectra could be reasonably resolved with the proviso that Fe2 O3 , FeO(OH), MnO(OH), and Mn2 O3 are the predominant Fe and Mn species on the surface of the oxidized steel S235. PMID- 26276388 TI - Unifying the DNA end-processing roles of the artemis nuclease: Ku-dependent artemis resection at blunt DNA ends. AB - Artemis is a member of the metallo-beta-lactamase protein family of nucleases. It is essential in vertebrates because, during V(D)J recombination, the RAG complex generates hairpins when it creates the double strand breaks at V, D, and J segments, and Artemis is required to open the hairpins so that they can be joined. Artemis is a diverse endo- and exonuclease, and creating a unified model for its wide range of nuclease properties has been challenging. Here we show that Artemis resects iteratively into blunt DNA ends with an efficiency that reflects the AT-richness of the DNA end. GC-rich ends are not cut by Artemis alone because of a requirement for DNA end breathing (and confirmed using fixed pseudo-Y structures). All DNA ends are cut when both the DNA-dependent protein kinase catalytic subunit and Ku accompany Artemis but not when Ku is omitted. These are the first biochemical data demonstrating a Ku dependence of Artemis action on DNA ends of any configuration. The action of Artemis at blunt DNA ends is slower than at overhangs, consistent with a requirement for a slow DNA end breathing step preceding the cut. The AT sequence dependence, the order of strand cutting, the length of the cuts, and the Ku-dependence of Artemis action at blunt ends can be reconciled with the other nucleolytic properties of both Artemis and Artemis.DNA PKcs in a model incorporating DNA end breathing of blunt ends to form transient single to double strand boundaries that have structural similarities to hairpins and fixed 5' and 3' overhangs. PMID- 26276389 TI - Structural Basis for the ATP-dependent Configuration of Adenylation Active Site in Bacillus subtilis o-Succinylbenzoyl-CoA Synthetase. AB - o-Succinylbenzoyl-CoA synthetase, or MenE, is an essential adenylate-forming enzyme targeted for development of novel antibiotics in the menaquinone biosynthesis. Using its crystal structures in a ligand-free form or in complex with nucleotides, a conserved pattern is identified in the interaction between ATP and adenylating enzymes, including acyl/aryl-CoA synthetases, adenylation domains of nonribosomal peptide synthetases, and luciferases. It involves tight gripping interactions of the phosphate-binding loop (P-loop) with the ATP triphosphate moiety and an open-closed conformational change to form a compact adenylation active site. In MenE catalysis, this ATP-enzyme interaction creates a new binding site for the carboxylate substrate, allowing revelation of the determinants of substrate specificities and in-line alignment of the two substrates for backside nucleophilic substitution reaction by molecular modeling. In addition, the ATP-enzyme interaction is suggested to play a crucial catalytic role by mutation of the P-loop residues hydrogen-bonded to ATP. Moreover, the ATP enzyme interaction has also clarified the positioning and catalytic role of a conserved lysine residue in stabilization of the transition state. These findings provide new insights into the adenylation half-reaction in the domain alteration catalytic mechanism of the adenylate-forming enzymes. PMID- 26276390 TI - The IVVY Motif and Tumor Necrosis Factor Receptor-associated Factor (TRAF) Sites in the Cytoplasmic Domain of the Receptor Activator of Nuclear Factor kappaB (RANK) Cooperate to Induce Osteoclastogenesis. AB - Receptor activator of NF-kappaB (RANK) activation by RANK ligand (RANKL) mediates osteoclastogenesis by recruiting TNF receptor-associated factors (TRAFs) via three cytoplasmic motifs (motif 1, PFQEP(369-373); motif 2, PVQEET(559-564); and motif 3, PVQEQG(604-609)) to activate the NF-kappaB and MAPK signaling pathways. RANK also has a TRAF-independent motif (IVVY(535-538)), which is dispensable for the activation of TRAF-induced signaling pathways but essential for osteoclast lineage commitment by inducing the expression of nuclear factor of activated T cells c1 (NFATc1) to regulate osteoclast gene expression. Notably, TNF/IL-1 mediated osteoclastogenesis requires RANK ligand assistance, and the IVVY motif is also critical for TNF/IL-1-mediated osteoclastogenesis by rendering osteoclast genes responsive to these two cytokines. Here we show that the two types of RANK cytoplasmic motifs have to be on the same RANK molecule to mediate osteoclastogenesis, suggesting a functional cooperation between them. Subsequent osteoclastogenesis assays with TNF or IL-1 revealed that, although all three TRAF motifs play roles in TNF/IL-1-mediated osteoclastogenesis, motifs 2 and 3 are more potent than motif 1. Accordingly, inactivation of motifs 2 and 3 blocksTNF/IL-1-mediated osteoclastogenesis. Mechanistically, double mutation of motifs 2 and 3, similar to inactivation of the IVVY motif, abrogates the expression of nuclear factor of activated T-cells c1 and osteoclast genes in assays reflecting RANK-initiated and TNF/IL-1-mediated osteoclastogenesis. In contrast, double inactivation of motifs 2 and 3 did not affect the ability of RANK to activate the NF-kappaB and MAPK signaling pathways. Collectively, these results indicate that the RANK IVVY motif cooperates with the TRAF-binding motifs to promote osteoclastogenesis, which provides novel insights into the molecular mechanism of RANK signaling in osteoclastogenesis. PMID- 26276391 TI - Prolyl isomerase Pin1 negatively regulates AMP-activated protein kinase (AMPK) by associating with the CBS domain in the gamma subunit. AB - AMP-activated protein kinase (AMPK) plays a critical role in metabolic regulation. In this study, first, it was revealed that Pin1 associates with any isoform of gamma, but not with either the alpha or the beta subunit, of AMPK. The association between Pin1 and the AMPK gamma1 subunit is mediated by the WW domain of Pin1 and the Thr(211)-Pro-containing motif located in the CBS domain of the gamma1 subunit. Importantly, overexpression of Pin1 suppressed AMPK phosphorylation in response to either 2-deoxyglucose or biguanide stimulation, whereas Pin1 knockdown by siRNAs or treatment with Pin1 inhibitors enhanced it. The experiments using recombinant Pin1, AMPK, LKB1, and PP2C proteins revealed that the protective effect of AMP against PP2C-induced AMPKalpha subunit dephosphorylation was markedly suppressed by the addition of Pin1. In good agreement with the in vitro data, the level of AMPK phosphorylation as well as the expressions of mitochondria-related genes, such as PGC-1alpha, which are known to be positively regulated by AMPK, were markedly higher with reduced triglyceride accumulation in the muscles of Pin1 KO mice as compared with controls. These findings suggest that Pin1 plays an important role in the pathogenic mechanisms underlying impaired glucose and lipid metabolism, functioning as a negative regulator of AMPK. PMID- 26276392 TI - AMP-activated protein kinase suppresses arachidonate 15-lipoxygenase expression in interleukin 4-polarized human macrophages. AB - Macrophages respond to the Th2 cytokine IL-4 with elevated expression of arachidonate 15-lipoxygenase (ALOX15). Although IL-4 signaling elicits anti inflammatory responses, 15-lipoxygenase may either support or inhibit inflammatory processes in a context-dependent manner. AMP-activated protein kinase (AMPK) is a metabolic sensor/regulator that supports an anti-inflammatory macrophage phenotype. How AMPK activation is linked to IL-4-elicited gene signatures remains unexplored. Using primary human macrophages stimulated with IL 4, we observed elevated ALOX15 mRNA and protein expression, which was attenuated by AMPK activation. AMPK activators, e.g. phenformin and aminoimidazole-4 carboxamide 1-beta-d-ribofuranoside inhibited IL-4-evoked activation of STAT3 while leaving activation of STAT6 and induction of typical IL-4-responsive genes intact. In addition, phenformin prevented IL-4-induced association of STAT6 and Lys-9 acetylation of histone H3 at the ALOX15 promoter. Activating AMPK abolished cellular production of 15-lipoxygenase arachidonic acid metabolites in IL-4 stimulated macrophages, which was mimicked by ALOX15 knockdown. Finally, pretreatment of macrophages with IL-4 for 48 h increased the mRNA expression of the proinflammatory cytokines IL-6, IL-12, CXCL9, and CXCL10 induced by subsequent stimulation with lipopolysaccharide. This response was attenuated by inhibition of ALOX15 or activation of AMPK during incubation with IL-4. In conclusion, limiting ALOX15 expression by AMPK may promote an anti-inflammatory phenotype of IL-4-stimulated human macrophages. PMID- 26276393 TI - Mycobacterium tuberculosis RecG protein but not RuvAB or RecA protein is efficient at remodeling the stalled replication forks: implications for multiple mechanisms of replication restart in mycobacteria. AB - Aberrant DNA replication, defects in the protection, and restart of stalled replication forks are major causes of genome instability in all organisms. Replication fork reversal is emerging as an evolutionarily conserved physiological response for restart of stalled forks. Escherichia coli RecG, RuvAB, and RecA proteins have been shown to reverse the model replication fork structures in vitro. However, the pathways and the mechanisms by which Mycobacterium tuberculosis, a slow growing human pathogen, responds to different types of replication stress and DNA damage are unclear. Here, we show that M. tuberculosis RecG rescues E. coli DeltarecG cells from replicative stress. The purified M. tuberculosis RecG (MtRecG) and RuvAB (MtRuvAB) proteins catalyze fork reversal of model replication fork structures with and without a leading strand single-stranded DNA gap. Interestingly, single-stranded DNA-binding protein suppresses the MtRecG- and MtRuvAB-mediated fork reversal with substrates that contain lagging strand gap. Notably, our comparative studies with fork structures containing template damage and template switching mechanism of lesion bypass reveal that MtRecG but not MtRuvAB or MtRecA is proficient in driving the fork reversal. Finally, unlike MtRuvAB, we find that MtRecG drives efficient reversal of forks when fork structures are tightly bound by protein. These results provide direct evidence and valuable insights into the underlying mechanism of MtRecG catalyzed replication fork remodeling and restart pathways in vivo. PMID- 26276395 TI - Suppressive effect of membrane-permeable peptides derived from autophosphorylation sites of the IGF-1 receptor on breast cancer cells. AB - Insulin-like growth factor-1 (IGF-1) receptors play a crucial role in the biology of human cancer, making them an attractive target for anti-cancer agents. We previously designed oligopeptides containing the amino-acid sequences surrounding the autophosphorylation sites of the insulin receptor and found that two of them, namely, Ac-DIYET-NH2 and Ac-DYYRK-NH2, suppressed phosphorylation of purified insulin receptors in a non-ATP-competitive manner, whereas Ac-NIYQT-NH2 and Ac NYYRK-NH2 suppressed in an ATP-competitive manner. Because the IGF-1 receptor is closely related to the insulin receptor, the aim of this study was to observe the effects of these peptides, which correspond to the amino-acid sequences of the autophosphorylation sites of the IGF-1 receptor, on the activity of the human breast cancer cell lines MCF-7, T47D, MDA-MB-231, and MDA-MB-453. To facilitate peptide delivery into breast cancer cells, the cell-penetrating peptide, human immunodeficiency virus type 1-transactivator of transcription (Tat), was linked to these peptides. When breast cancer cells were treated with each of these synthetic Tat-conjugated peptides, the conjugated peptides penetrated into the cells and suppressed cell proliferation. An inhibitory effect of Tat-conjugated peptides against IGF-1-stimulated phosphorylation of IGF-1 receptors was observed. In addition, we found that combinations of these peptides suppressed phosphorylation of IGF-1 receptors to a greater extent than the peptides did individually. In conclusion, IGF-1 receptor autophosphorylation site-derived membrane-permeable peptides have the potential to suppress IGF-1 receptor function in breast cancer cells and to be developed into novel and useful agents for cancer therapy. PMID- 26276394 TI - Mechanisms of inhibition and potentiation of alpha4beta2 nicotinic acetylcholine receptors by members of the Ly6 protein family. AB - alpha4beta2 nicotinic acetylcholine receptors (nAChRs) are abundantly expressed throughout the central nervous system and are thought to be the primary target of nicotine, the main addictive substance in cigarette smoking. Understanding the mechanisms by which these receptors are regulated may assist in developing compounds to selectively interfere with nicotine addiction. Here we report previously unrecognized modulatory properties of members of the Ly6 protein family on alpha4beta2 nAChRs. Using a FRET-based Ca(2+) flux assay, we found that the maximum response of alpha4beta2 receptors to agonist was strongly inhibited by Ly6h and Lynx2 but potentiated by Ly6g6e. The mechanisms underlying these opposing effects appear to be fundamentally distinct. Receptor inhibition by Lynx2 was accompanied by suppression of alpha4beta2 expression at the cell surface, even when assays were preceded by chronic exposure of cells to an established chaperone, nicotine. Receptor inhibition by Lynx2 also was resistant to pretreatment with extracellular phospholipase C, which cleaves lipid moieties like those that attach Ly6 proteins to the plasma membrane. In contrast, potentiation of alpha4beta2 activity by Ly6g6e was readily reversible by pretreatment with phospholipase C. Potentiation was also accompanied by slowing of receptor desensitization and an increase in peak currents. Collectively our data support roles for Lynx2 and Ly6g6e in intracellular trafficking and allosteric potentiation of alpha4beta2 nAChRs, respectively. PMID- 26276396 TI - Cardiovascular protection by ezetimibe and influence on oxidative stress in mice exposed to intermittent hypoxia. AB - Ezetimibe is as an inhibitor of NPC1L1 protein, which has a key role in cholesterol absorption. The aim of this study was to evaluate the influence of ezetimibe on the plasma lipid profile, atherosclerotic lesions, and cardiomyocyte ultrastructure in an animal model of atherosclerosis with intermittent hypoxia. Apolipoprotein E-knockout mice received a high-fat diet for 30 days. Then animals were exposed to intermittent hypoxia for 10 days or were maintained under normoxic conditions. In the ezetimibe group, ezetimibe (5 mg/kg/day) was added to the diet. Under normoxic conditions, the total cholesterol level was significantly lower in the ezetimibe group (63.6+/-6.6 mg/dl) than in the control group (116.3+/-16.9 mg/dl, P<0.001). Intermittent hypoxia accelerated atherosclerosis associated with increased superoxide production, which also caused degeneration of cardiomyocytes, mitochondrial abnormalities, and interstitial fibrosis. Compared with the control group, the ezetimibe group showed significantly less advanced atherosclerotic lesions and lower superoxide production in the thoracic aorta, as well as reduced oxidative stress, preservation of cardiomyocyte ultrastructure, and reduced interstitial fibrosis in the left ventricular myocardium. In conclusion, ezetimibe not only reduces total cholesterol, but also prevents the development of atherosclerosis and cardiovascular events due to intermittent hypoxia at least partly through suppression of oxidative stress. PMID- 26276397 TI - Sample size considerations for livestock movement network data. AB - The movement of animals between farms contributes to infectious disease spread in production animal populations, and is increasingly investigated with social network analysis methods. Tangible outcomes of this work include the identification of high-risk premises for targeting surveillance or control programs. However, knowledge of the effect of sampling or incomplete network enumeration on these studies is limited. In this study, a simulation algorithm is presented that provides an estimate of required sampling proportions based on predicted network size, density and degree value distribution. The algorithm may be applied a priori to ensure network analyses based on sampled or incomplete data provide population estimates of known precision. Results demonstrate that, for network degree measures, sample size requirements vary with sampling method. The repeatability of the algorithm output under constant network and sampling criteria was found to be consistent for networks with at least 1000 nodes (in this case, farms). Where simulated networks can be constructed to closely mimic the true network in a target population, this algorithm provides a straightforward approach to determining sample size under a given sampling procedure for a network measure of interest. It can be used to tailor study designs of known precision, for investigating specific livestock movement networks and their impact on disease dissemination within populations. PMID- 26276398 TI - The economic impact of subclinical ketosis at the farm level: Tackling the challenge of over-estimation due to multiple interactions. AB - Subclinical ketosis (SCK) is a major metabolic disorder that affects dairy cows, and its lactational prevalence in Europe is estimated to be at 25%. Nonetheless, few data are available on the economics of SCK, although its management clearly must be improved. With this in mind, this study develops a double-step stochastic approach to evaluate the total cost of SCK to dairy farming. First, all the production and reproduction changes and all the health disorders associated with SCK were quantified using the meta-analysis from a previous study. Second, the total cost of SCK was determined with a stochastic model using distribution laws as input parameters. The mean total cost of SCK was estimated to be ?257 per calving cow with SCK (95% prediction interval (PI): ?72-442). The margin over feeding costs slightly influenced the results. When the parameters of the model are not modified to account for the conclusions from the meta-analysis and for the prevalence of health disorders in the population without SCK, the mean cost of SCK was overestimated by 68%, reaching ?434 per calving cow (95%PI: ?192-676). This result indicates that the total cost of complex health disorders is likely to be substantially overestimated when calculations use raw results from the literature or-even worse-punctual data. Excluding labour costs in the estimation reduced the SCK total cost by 12%, whereas excluding contributors with scarce data and imprecise calibrations (for lameness and udder health) reduced costs by another 18-20% (?210, 95%PI=30-390). The proposed method accounted for uncertainty and variability in inputs by using distributions instead of point estimates. The mean value and associated prediction intervals (PIs) yielded good insight into the economic consequences of this complex disease and can be easily and practically used by decision makers in the field while simultaneously accounting for biological variability. Moreover, PIs can help prevent the blind use of economic results in the field when only the mean value is considered. PMID- 26276399 TI - Hypothesis generation using network structures on community health center cancer screening performance. AB - RESEARCH OBJECTIVES: Nationally sponsored cancer-care quality-improvement efforts have been deployed in community health centers to increase breast, cervical, and colorectal cancer-screening rates among vulnerable populations. Despite several immediate and short-term gains, screening rates remain below national benchmark objectives. Overall improvement has been both difficult to sustain over time in some organizational settings and/or challenging to diffuse to other settings as repeatable best practices. Reasons for this include facility-level changes, which typically occur in dynamic organizational environments that are complex, adaptive, and unpredictable. This study seeks to understand the factors that shape community health center facility-level cancer-screening performance over time. This study applies a computational-modeling approach, combining principles of health-services research, health informatics, network theory, and systems science. METHODS: To investigate the roles of knowledge acquisition, retention, and sharing within the setting of the community health center and to examine their effects on the relationship between clinical decision support capabilities and improvement in cancer-screening rate improvement, we employed Construct-TM to create simulated community health centers using previously collected point-in time survey data. Construct-TM is a multi-agent model of network evolution. Because social, knowledge, and belief networks co-evolve, groups and organizations are treated as complex systems to capture the variability of human and organizational factors. In Construct-TM, individuals and groups interact by communicating, learning, and making decisions in a continuous cycle. Data from the survey was used to differentiate high-performing simulated community health centers from low-performing ones based on computer-based decision support usage and self-reported cancer-screening improvement. RESULTS: This virtual experiment revealed that patterns of overall network symmetry, agent cohesion, and connectedness varied by community health center performance level. Visual assessment of both the agent-to-agent knowledge sharing network and agent-to resource knowledge use network diagrams demonstrated that community health centers labeled as high performers typically showed higher levels of collaboration and cohesiveness among agent classes, faster knowledge-absorption rates, and fewer agents that were unconnected to key knowledge resources. Conclusions and research implications: Using the point-in-time survey data outlining community health center cancer-screening practices, our computational model successfully distinguished between high and low performers. Results indicated that high-performance environments displayed distinctive network characteristics in patterns of interaction among agents, as well as in the access and utilization of key knowledge resources. Our study demonstrated how non network-specific data obtained from a point-in-time survey can be employed to forecast community health center performance over time, thereby enhancing the sustainability of long-term strategic-improvement efforts. Our results revealed a strategic profile for community health center cancer-screening improvement via simulation over a projected 10-year period. The use of computational modeling allows additional inferential knowledge to be drawn from existing data when examining organizational performance in increasingly complex environments. PMID- 26276400 TI - Hydrothermal liquefaction of de-oiled Jatropha curcas cake using Deep Eutectic Solvents (DESs) as catalysts and co-solvents. AB - Biomass liquefaction using ionic liquids (ILs) as catalysts has received appreciable attention, in renewable fuels and chemicals production, recently. However, issues associated with the production cost, long reaction time and use of volatile solvents are undeniably challenging. Thus, Deep Eutectic Solvents (DESs) emerged as promising and potential ILs substitutes. The hydrothermal liquefaction of de-oiled Jatropha curcas cake was catalyzed by four synthesized DESs as catalysts and co-solvents for selective extraction. Proximate and ultimate analyses including ash, moisture and carbon contents of bio-crude produced varied slightly. The higher heating values found ranges from 21.15 +/- 0.82 MJ/kg to 24.30 +/- 0.98 MJ/kg. The bio-crude yields obtained using ChCl-KOH DES was 43.53 wt% and ChCl-p-TsOH DES was 38.31 wt%. Bio-crude yield using ChCl FeCl3 DES was 30.80 wt%. It is suggested that, the selectivity of bio-crude could be improved, by using DESs as catalyst and co-solvent in HTL of biomass such as de-oiled J. curcas cake. PMID- 26276401 TI - Pretreatment and saccharification of red macroalgae to produce fermentable sugars. AB - Red macroalgae are currently considered as renewable resources owing to their high carbohydrate and low lignin and hemicellulose contents. However, utilization of red macroalgae has been limited owing to the lack of established methods for pretreatment and an effective saccharification system. Furthermore, marine red macroalgae consist of the non-favorable mixed sugars for industrial microorganisms. In this review, we suggest strategies for converting red macroalgae to bio-based products, focusing on the pretreatment and saccharification of red macroalgae to produce fermentable sugars and the microbial fermentation of these sugars by industrial microorganisms. In particular, some recent breakthroughs for the efficient utilization of red macroalgae include the discovery of key enzymes for the complete monomerization of red macroalgal carbohydrate and the catabolic pathway of 3,6-anhydro-l galactose, the most abundant sugar in red macroalgae. This review provides a comprehensive perspective for the efficient utilization of red macroalgae as sustainable resources to produce bio-based products. PMID- 26276402 TI - Effect of temperature on biomass allocation in seedlings of two contrasting genotypes of the oilseed crop Ricinus communis. AB - Ricinus communis is becoming an important crop for oil production, and studying the physiological and biochemical aspects of seedling development may aid in the improvement of crop quality and yield. The objective of this study was to assess the effect of temperature on biomass allocation in two R. communis genotypes. Biomass allocation was assessed by measuring dry weight of roots, stems, and cotyledons of seedlings grown at three different temperatures. Root length of each seedling was measured. Biomass allocation was strongly affected by temperature. Seedlings grown at 25 degrees C and 35 degrees C showed greater biomass than seedlings grown at 20 degrees C. Cotyledon and stem dry weight increased for both genotypes with increasing temperature, whereas root biomass allocation showed a genotype-dependent behavior. Genotype MPA11 showed a continuous increase in root dry weight with increasing temperature, while genotype IAC80 was not able to sustain further root growth at higher temperatures. Based on metabolite and gene expression profiles, genotype MPA11 increases its level of osmoprotectant molecules and transcripts of genes encoding for antioxidant enzymes and heat shock proteins to a higher extent than genotype IAC80. This might be causal for the ability to maintain homeostasis and support root growth at elevated temperatures in genotype MPA11. PMID- 26276403 TI - Accumulation of flavonoids and phenolic compounds in olive tree roots in response to mycorrhizal colonization: A possible mechanism for regulation of defense molecules. AB - The arbuscular mycorrhizal (AM) fungus promotes plant growth and can alter the production of primary and secondary metabolites. The aim of this work was to determine the influence of AM fungi colonization on the content of phenolic compounds, flavonoids and soluble carbohydrates in olive (Olea europaea L.) tree roots. The results revealed that mycorrhizal plants had a higher content of flavonoids and total phenols. Analysis of sugar contents showed enhanced levels of sucrose and fructose in mycorrhizal roots, while glucose amounts stayed constant. The DPPH radical-scavenging activity of the mycorrhizal root methanolic extracts was higher than that of the non- mycorrhizal root methanolic extracts. These results indicated that olive tree roots contain significant amounts of phenolic compounds, important factors for antioxidant capacity, which can be substantially modified by colonization of olive trees with AM fungi. PMID- 26276404 TI - Identification and characterization of a gene encoding for a nucleotidase from Phaseolus vulgaris. AB - Nucleotidases are phosphatases that catalyze the removal of phosphate from nucleotides, compounds with an important role in plant metabolism. A phosphatase enzyme, with high affinity for nucleotides monophosphate previously identified and purified in embryonic axes from French bean, has been analyzed by MALDI TOF/TOF and two internal peptides have been obtained. The information of these peptide sequences has been used to search in the genome database and only a candidate gene that encodes for the phosphatase was identified (PvNTD1). The putative protein contains the conserved domains (motif I-IV) for haloacid dehalogenase-like hydrolases superfamily. The residues involved in the catalytic activity are also conserved. A recombinant protein overexpressed in Escherichia coli has shown molybdate resistant phosphatase activity with nucleosides monophosphate as substrate, confirming that the identified gene encodes for the phosphatase with high affinity for nucleotides purified in French bean embryonic axes. The activity of the purified protein was inhibited by adenosine. The expression of PvNTD1 gene was induced at the specific moment of radicle protrusion in embryonic axes. The gene was also highly expressed in young leaves whereas the level of expression in mature tissues was minimal. PMID- 26276405 TI - Veinal-mesophyll interaction under biotic stress. AB - According to microscopic observations, germinating hyphae of Botrytis cinerea, though easily penetrating Mesembryanthemum crystallinum mesophyll tissue, are limited in growth in mid-ribs and only occasionally reach vascular bundles. In mid-ribs of C3 and CAM leaves, we found significantly lower rbcL (large RubisCO subunit) abundance. Moreover, in CAM leaves, minute transcript contents for pepc1 (phosphoenolpyruvate carboxylase) and nadpme1 (malic enzyme) genes found in the mid-ribs suggest that they perform beta-carboxylation at a low rate. The gene of the main H2O2-scavenging enzyme, catL (catalase), showed lower expression in C3 mid-rib parts in comparison to mesophyll. This allows maintenance of higher H2O2 quantities in mid-rib parts. In C3 leaves, pathogen infection does not impact photosynthesis. However, in CAM plants, the expression profiles of rbcL and nadpme1 were similar under biotic stress, with transcript down-regulation in mid ribs and up-regulation in mesophyll (however, in case of rbcL not significant). After B. cinerea infection in C3 plants, transcripts for both antioxidative proteins strongly increased in mid-ribs, but not in mesophyll. In infected CAM plants, a significant transcript increase in the mesophyll was parallel to its decrease in the mid-rib region (however, in the case of catL this was not significant). Pathogen infection modified the expression of carbon and ROS metabolism genes in mid-ribs and mesophyll, resulting in the establishment of successful leaf defense. PMID- 26276406 TI - [Adult pattern of alcohol use as perceived by adolescents]. AB - OBJECTIVE: To identify the views of a sample of adolescents on the pattern of alcohol consumption shown by adults in their social environment. METHOD: A qualitative study was conducted using the method proposed by grounded theory (Glaser & Strauss, 1967). Data were collected through five discussion groups. Participants were selected by theoretical sampling in the initial and emerging phases of the study by applying criteria based on previous research. Heterogeneity-homogeneity criteria were used in the composition of the groups. The final sample consisted on 40 adolescents of both sexes between 15 and 20 years from four educational centres in Seville (Spain). RESULTS: According to the adolescents interviewed, alcohol use was normal among adults, geared towards fun, and was linked to social gatherings and to abusive and intensive consumption including drinking spirits. Data from recent studies partly contradict adolescents' perceptions, showing a pattern of consumption in adults associated mostly with the gastronomic and social component of drink and with moderate intake of beer and wine. CONCLUSIONS: The results of this study suggest that adolescents may have a distorted view of the reality of adult patterns of alcohol use. As an explanation, we hypothesize that, faced with conflicting information, adolescents prioritize the information that best fits their view of what is socially acceptable and what meets their own hedonistic and social needs. PMID- 26276407 TI - Accelerating total body irradiation with large field modulated arc therapy in standard treatment rooms without additional equipment. AB - PURPOSE: The aim of this study was to develop a generic and ultra-efficient modulated arc technique for treatment with total body irradiation (TBI) without additional equipment in standard treatment rooms. METHODS: A continuous gantry arc between 300 degrees and 70 degrees composed of 26 subarcs (5 degrees per subarc) using a field size of 40 * 40 cm(2) was used to perform the initial beam data measurements. The profile was measured parallel to the direction of gantry rotation at a constant depth of 9 cm (phantom thickness 18 cm). Beam data were measured for single 5 degrees subarcs, dissecting the individual contribution of each subarc to a certain measurement point. The phantom was moved to 20 measurement positions along the profile. Then profile optimization was performed manually by varying the weighting factors of all segments until calculated doses at all points were within +/- 1 %. Finally, the dose distribution of the modulated arc was verified in phantom thicknesses of 18 and 28 cm. RESULTS: The measured profile showed a relative mean dose of 99.7 % [standard deviation (SD) 0.7 %)] over the length of 200 cm at a depth of 9 cm. The measured mean effective surface dose (at a depth of 2 cm) was 102.7 % (SD 2.1 %). The measurements in the 28 cm slab phantom revealed a mean dose of 95.9 % (SD 2.9 %) at a depth of 14 cm. The mean dose at a depth of 2 cm was 111.9 % (SD 4.1 %). Net beam-on-time for a 2 Gy fraction is approximately 8 min. CONCLUSION: This highly efficient modulated arc technique for TBI can replace conventional treatment techniques, providing a homogeneous dose distribution, dosimetric robustness, extremely fast delivery, and applicability in small treatment rooms, with no need for additional equipment. PMID- 26276408 TI - Duodenal gastrointestinal stromal tumors: clinicopathological characteristics, surgery, and long-term outcome. AB - BACKGROUND: Duodenal gastrointestinal stromal tumors (DGIST) are rare, and data on their management is limited. We here report the clinicopathological characteristics, different surgical treatments, and long-term prognosis of DGIST. METHODS: Data of 74 consecutive patients with DGIST in a single institution from June 2000 to June 2014 were retrospectively analyzed. The overall survival (OS) and recurrence/metastasis-free survival rates of 74 cases were calculated using Kaplan-Meier method. RESULTS: Out of 74 cases, 42 cases were female (56.76%) and 32 cases (43.24%) were male. Approximately 22.97, 47.30, 16.22, and 13.51% of the tumors originated in the first to fourth portion of the duodenum, respectively, with a tumor size of 5.08 +/- 2.90 cm. Patients presented with gastrointestinal bleeding (n = 37, 50.00%), abdominal pain (n = 25, 33.78 %), mass (n = 5, 6.76%), and others (n = 7, 9.76%). A total of 18 patients (24.3%) underwent wedge resection (WR); 39 patients (52.7%) underwent segmental resection (SR); and 17 cases (23%) underwent pancreaticoduodenectomy (PD). The median follow-up was 56 months (1-159 months); 19 patients (25.68%) experienced tumor recurrence or metastasis, and 14 cases (18.92 %) died. The 1-, 3-, and 5-year recurrence/metastasis-free survival rates were 93.9, 73.7, and 69%, respectively. The 1-, 3- and 5-year OS were 100, 92.5, and 86%, respectively. The recurrence/metastasis-free survival rate in the PD group within 5 years was lower than that in the WR group (P = 0.047), but was not different from that in the SR group (P = 0.060). No statistically significant difference was found among the three operation types (P = 0.294). CONCLUSIONS: DGIST patients have favorable prognosis after complete tumor removal, and surgical procedures should be determined by the DGIST tumor location and size. PMID- 26276409 TI - Interference Competition Among Household Strains of Pseudomonas. AB - Bacterial species exhibit biogeographical patterns like those observed in larger organisms. The distribution of bacterial species is driven by environmental selection through abiotic and biotic factors as well dispersal limitations. We asked whether interference competition, a biotic factor, could explain variability in habitat use by Pseudomonas species in the human home. To answer this question, we screened almost 8000 directional, pairwise interactions between 89 Pseudomonas strains including members of the Pseudomonas aeruginosa (n = 29), Pseudomonas fluorescens (n = 21), and Pseudomonas putida (n = 39) species groups for the presence of killing. This diverse set of Pseudomonas strains includes those isolated from several different habitats within the home environment and includes combinations of strains that were isolated from different spatial scales. The use of this strain set not only allowed us to analyze the commonality and phylogenetic scale of interference competition within the genus Pseudomonas but also allowed us to investigate the influence of spatial scale on this trait. Overall, the probability of killing was found to decrease with increasing phylogenetic distance, making it unlikely that interference competition accounts for previously observed differential habitat use among Pseudomonas species and species groups. Strikingly, conspecific P. aeruginosa killing accounted for the vast majority of the observed killing, and this killing was found to differ across the habitat type and spatial scale of the strains' isolation. These data suggest that interference competition likely plays a large role in the within species dynamics of P. aeruginosa but not other household Pseudomonas species. PMID- 26276411 TI - Effective Boolean dynamics analysis to identify functionally important genes in large-scale signaling networks. AB - Efficiently identifying functionally important genes in order to understand the minimal requirements of normal cellular development is challenging. To this end, a variety of structural measures have been proposed and their effectiveness has been investigated in recent literature; however, few studies have shown the effectiveness of dynamics-based measures. This led us to investigate a dynamic measure to identify functionally important genes, and the effectiveness of which was verified through application on two large-scale human signaling networks. We specifically consider Boolean sensitivity-based dynamics against an update-rule perturbation (BSU) as a dynamic measure. Through investigations on two large scale human signaling networks, we found that genes with relatively high BSU values show slower evolutionary rate and higher proportions of essential genes and drug targets than other genes. Gene-ontology analysis showed clear differences between the former and latter groups of genes. Furthermore, we compare the identification accuracies of essential genes and drug targets via BSU and five well-known structural measures. Although BSU did not always show the best performance, it effectively identified the putative set of genes, which is significantly different from the results obtained via the structural measures. Most interestingly, BSU showed the highest synergy effect in identifying the functionally important genes in conjunction with other measures. Our results imply that Boolean-sensitive dynamics can be used as a measure to effectively identify functionally important genes in signaling networks. PMID- 26276410 TI - Molecular Ecology of nifH Genes and Transcripts Along a Chronosequence in Revegetated Areas of the Tengger Desert. AB - The colonization and succession of diazotrophs are essential for the development of organic soil layers in desert. We examined the succession of diazotrophs in the well-established revegetated areas representing a chronosequence of 0 year (control), 22 years (restored artificially since 1981), 57 years (restored artificially since 1956), and more than 100 years (restored naturally) to determine the community assembly and active expression of diazotrophs. The pyrosequencing data revealed that Alphaproteobacteria-like diazotrophs predominated in the topsoil of our mobile dune site, while cyanobacterial diazotrophs predominated in the revegetated sites. The cyanobacterial diazotrophs were primarily composed of the heterocystous genera Anabaena, Calothrix, Cylindrospermum, Nodularia, Nostoc, Trichormus, and Mastigocladus. Almost all the nifH sequences belonged to the Cyanobacteria phylum (all the relative abundance values >99.1 %) at transcript level and all the active cyanobacterial diazotrophs distributed in the families Nostocaceae and Rivulariaceae. The most dominant active cyanobacterial genus was Cylindrospermum in all the samples. The rank abundance and community analyses demonstrated that most of the diazotrophic diversity originated from the "rare" species, and all the DNA-based diazotrophic libraries were richer and more diverse than their RNA-based counterparts in the revegetated sites. Significant differences in the diazotrophic community and their active population composition were observed among the four research sites. Samples from the 1981-revegetating site (predominated by cyanobacterial crusts) showed the highest nitrogenase activity, followed by samples from the naturally revegetating site (predominated by lichen crusts), the 1956-revegetating site (predominated by moss crusts), and the mobile dune site (without crusts). Collectively, our data highlight the importance of nitrogen fixation by the primary successional desert topsoil and suggest that the N2-fixing cyanobacteria are the key diazotrophs to the nitrogen budget and the development of topsoil in desert, which is critical for the succession of the degraded terrestrial ecosystems. PMID- 26276412 TI - On the Cramer-Rao bound applicability and the role of Fisher information in computational neuroscience. AB - Neuronal systems exhibit impressive capabilities in decision making and action coordination by employing the encoded information about both external and internal environments. Despite the tremendous effort of neuroscientists, the exact nature of the neuronal code remains elusive. Various experimental and theoretical techniques have been used to resolve the question in recent decades, with methods of signal estimation and detection theory playing an important part. In this paper we review the particular approach which relies on the concepts of Fisher information and Cramer-Rao bound. These concepts essentially investigate the neuronal coding problem by addressing the theoretical limits on the decoding precision, be it in single neurons or in their populations. Despite the success of this approach in many instances, the underlying mathematical theory is not free of certain restrictive assumptions which might complicate the inference in some cases of interest. We recapitulate the assumptions and examine the practical extent of their validity. PMID- 26276413 TI - Does F-18 FDG-PET substantially alter the surgical decision-making in drug resistant partial epilepsy? AB - OBJECTIVE: There is a dearth of information on the critical utility of positron emission tomography (PET) in choosing candidates for epilepsy surgery especially in resource-poor countries where it is not freely available. This study aimed to critically analyze the utility of FDG-PET in the presurgical evaluation and surgical selection of patients with DRE based on the results obtained through its use in our comprehensive epilepsy program. METHODS: From 2008 to 2012, 117 patients with drug-resistant epilepsy underwent F-18 fluoro-deoxy-glucose (FDG) PET in our center. We utilized their data to audit the utility of PET in choosing/deferring patients for surgery. RESULTS: Of the 117 patients (age: 5 42years) who underwent F-18 FDG-PET, 64 had normal MRI, and 53 had lesions. Electroclinical data favored temporal ictal onset in 48 (41%), extratemporal in 60 (51.3%), and uncertain lobar localization in 9 (7.7%). The topography of PET hypometabolism was localizing in 53 (45.3%), lateralizing in 12 (10.3%), and 52 (44.4%) had either normal or discordant results. In the nonlesional group, focal hypometabolism was concordant to the area of ictal onset in 27 (41.5%) versus 38 (58.5%) in the lesional group (p=0.002). Greater concordance was noted in temporal lobe epilepsy (TLE) (78.0%) as compared to extratemporal epilepsy (ETPE) (28.6%) (p<0.001). Positron emission tomography was more concordant in patients with mesial temporal sclerosis than in those with other lesions (82.8% versus 50%) (p=0.033). Positron emission tomography helped in surgical decision-making in 68.8% of TLE and 23.3% of ETPE cases. Overall, 37 patients (31.6%) were directly selected for resective surgery based on PET results. CONCLUSIONS: Positron emission tomography, when utilized judiciously, remained an ancillary tool in the surgical selection of one-third of patients with drug-resistant partial epilepsy, although its utility as an independent tool is not very promising. PMID- 26276414 TI - Two years after epilepsy surgery in children: Recognition of emotions expressed by faces. AB - OBJECTIVES: The purpose of this study was to determine whether children with epilepsy surgery in their history are able to recognize emotions expressed by faces and whether this recognition is associated with demographic variables [age, sex, and verbal intelligence (VIQ)] and/or epilepsy variables (epilepsy duration, side of the surgery, surgery area, resection of the amygdala, etiology, antiepileptic drug use, and seizure freedom). METHODS: Two years after epilepsy surgery, the Facial Expression of Emotion: Stimuli and Tests (FEEST) was administered to 41 patients (age: 4-20years, mean: 13.5years, 24 girls) and 82 age- and sex-matched healthy controls. Data obtained longitudinally (before surgery and 6, 12, and 24months after surgery) in a small subset (11 patients and 22 matched controls) were explored to obtain clues about the course of REEF from before surgery. RESULTS: Corrected for VIQ, REEF scored significantly lower in the 41 surgically treated patients than in matched control children. No significant relationship was found between REEF and any epilepsy variable. Only age at assessment predicted REEF score in both patients and controls. The longitudinal data revealed a 'dip' in emotion recognition at the first postsurgical assessment in the six younger patients (age: <12.1years). The older patients (age: 13-17years) showed a continuous increase in REEF scores that was similar to that in controls. Two years after surgery, REEF of the younger patients recovered to, but did not exceed, the presurgical level. CONCLUSION: Neither poor REEF present two years after childhood epilepsy surgery, nor the aberrant course of REEF in younger patients (age: <12.1years) was explained by epilepsy variables or poor verbal intelligence. Disentangling the mechanism of the abnormality is urgently needed, as recognizing emotional expressions is a key component in the development of more complex social perception skills. PMID- 26276415 TI - Actinic keratosis: a cross-sectional study of disease characteristics and treatment patterns in Danish dermatology clinics. AB - OBJECTIVES: The incidence of actinic keratosis (AK) is increasing, and several treatment options are available. The aim of this study was to describe clinical characteristics and treatment patterns in patients with AK treated by Danish dermatologists. METHODS: A multicenter, non-interventional, cross-sectional study was conducted. Three dermatology hospital departments and seven private dermatology clinics enrolled eligible AK patients consecutively during one week. RESULTS: A total of 312 patients were included. Non-melanoma skin cancer (NMSC) was previously reported in 51.0% of patients and currently suspected in 9.4% of AK-affected anatomical regions. Lesions of AK were located primarily on the face (38.6%), scalp (12.8%), and hands (11.2%). Actinic keratosis commonly presented with multiple AK lesions (38.6%) and field cancerization (38.5%). The treatments used most frequently were cryotherapy (57.7%) and photodynamic therapy (PDT) with methyl aminolevulinate (17.1%) and imiquimod (11.2%). The likelihood of receiving cryotherapy was higher for men (odds ratio [OR] 1.65, 95% confidence interval [CI] 1.10-2.47) and increased with age (2.2% per year, 0.4-4.0%). PDT represented the most frequently applied treatment for severe actinic damage and was more likely to be prescribed to women (OR 4.08, 95% CI 2.22-7.47) and young patients (OR 0.97 per year, 95% CI 0.95-0.99). The prevalence of severe actinic damage (17.3% versus 9.6%) and intake of immunosuppressive medication (29.0 versus 2.0) were higher among hospital patients compared with those treated in private practices (P < 0.0001). CONCLUSIONS: The majority of AK patients in Danish dermatology clinics have a history of skin cancer, and NMSC is suspected in almost 10% of AK-affected regions. Cryotherapy is the most frequently used treatment overall, except in instances of severe actinic damage, in which PDT is the first-choice treatment. PMID- 26276416 TI - A model on how to obtain data from botanical practitioners. AB - OBJECTIVE: This paper addresses the challenge on how to obtain information from practitioners with experience in using medicinal plants. BACKGROUND: Collecting information on medicinal uses of plants is very challenging; since botanical remedies are used within the context of multiple differing medical systems, practitioners differ in training from Western physicians and scientists, and active ingredients of botanicals vary with preparation method, growth, and harvest conditions. DESIGN/METHODS: A model on how useful data on safety and efficacy can be obtained from botanical practitioners is presented, based on methods developed by the association of anthroposophic physicians in Europe, a system of integrative medicine which includes the use of botanicals and is practiced mostly by medical doctors. RESULTS: Decades of experience by hundreds of practitioners are summarized and made accessible in a manual, which alphabetically lists the most commonly used botanicals and describes the most successful therapeutic experiences which could be confirmed by several of the contributing practitioners. CONCLUSIONS/RELEVANCE: This approach of continuous, multilingual systematic collection of successful therapeutic experiences within a community of practitioners with similar goals and a common therapeutic framework can be used not only for the training of successful future botanical practitioners, but also for helping to identify promising botanicals for scientific research and to further their development, and could support their official registration with governing bodies in countries of their use. This article is part of a Special Issue entitled "Botanicals for Epilepsy". PMID- 26276418 TI - The pathophysiology of otosclerosis: Review of current research. AB - Otosclerosis is a complex disease of the human otic capsule with highest incidence in adult Caucasians. So far, many possible etiological factors like genetics, HLA, autoimmunity, viruses, inflammation, and hormones have been investigated but still the development of the disease remains unclear. Currently, the surgical replacement of stapes (stapedotomy) remains the best possible treatment option. In this review, we analyze different etiological factors studied so far in otosclerosis pathophysiology and discuss most recent findings and possible new research pathways. PMID- 26276419 TI - Effects of background noise on inter-trial phase coherence and auditory N1-P2 responses to speech stimuli. AB - This study investigated the effects of a speech-babble background noise on inter trial phase coherence (ITPC, also referred to as phase locking value (PLV)) and auditory event-related responses (AERP) to speech sounds. Specifically, we analyzed EEG data from 11 normal hearing subjects to examine whether ITPC can predict noise-induced variations in the obligatory N1-P2 complex response. N1-P2 amplitude and latency data were obtained for the /bu/syllable in quiet and noise listening conditions. ITPC data in delta, theta, and alpha frequency bands were calculated for the N1-P2 responses in the two passive listening conditions. Consistent with previous studies, background noise produced significant amplitude reduction and latency increase in N1 and P2, which were accompanied by significant ITPC decreases in all the three frequency bands. Correlation analyses further revealed that variations in ITPC were able to predict the amplitude and latency variations in N1-P2. The results suggest that trial-by-trial analysis of cortical neural synchrony is a valuable tool in understanding the modulatory effects of background noise on AERP measures. PMID- 26276417 TI - Third International Congress on Epilepsy, Brain and Mind: Part 1. AB - Epilepsy is both a disease of the brain and the mind. Here, we present the first of two papers with extended summaries of selected presentations of the Third International Congress on Epilepsy, Brain and Mind (April 3-5, 2014; Brno, Czech Republic). Epilepsy in history and the arts and its relationships with religion were discussed, as were overviews of epilepsy and relevant aspects of social cognition, handedness, accelerated forgetting and autobiographical amnesia, and large-scale brain networks. PMID- 26276420 TI - Implementing Substance Abuse Intervention Services in New York City Sexually Transmitted Disease Clinics: Factors Promoting Interagency Collaboration. AB - This report presents results of Project LINK, a Substance Abuse and Mental Health Services Administration (SAMHSA)-funded, 5-year collaboration (2007-2012) between New York City (NYC) health and NY State substance abuse disorder (SUD) agencies, an LGBT organization contractor, and multiple SUD, social service, and mental health referral agencies. LINK allowed the first ever SUD screening, brief intervention, and referrals to treatment (SBIRT) intervention services onsite in NYC Bureau of Sexually Transmitted Disease Control (BSTDC) clinics. Factors favoring collaboration were (a) joint recognition of substance abuse as an STD risk factor; (b) prior collaborations; (c) agreement on priority of BSTDC's mission and policies; (d) extensive SBIRT training, cross training on STDs; (e) a memorandum of agreement; and (f) mutual transparency of collaborative efforts, among others. LINK screened over 151,000 STD clinic patients and delivered brief interventions to 60% of positively screened patients and met a mandated follow-up target. Factors found to facilitate collaboration here may help screen prospective new health collaborations. PMID- 26276421 TI - Private Health Plans' Contracts with Managed Behavioral Healthcare Organizations. PMID- 26276422 TI - Postpartum Traditions, Mental Health, and Help-Seeking Considerations Among Vietnamese American Women: a Mixed-Methods Pilot Study. AB - The purpose of this study was to explore Vietnamese American mothers' perceptions and experiences with postpartum traditions, postpartum depression (PPD), and mental health help-seeking behavior. Participants were 15 Vietnamese mothers who had given birth to at least one live infant within the previous year. A screening tool revealed that a third of the mothers had probable PPD. More than half reported having recent/current postpartum "sadness" during the interviews. Postpartum traditions played important roles in their well-being and maintaining strong cultural values. However, some reported feelings of isolation and the desire to be able to carry out postpartum traditions more frequently. Many who had reported sadness said that they would not seek professional help; all had felt that their condition was not "severe" enough to warrant help-seeking. Future PPD interventions should consider the importance of postpartum cultural traditions and address help-seeking barriers as ways to prevent the adverse effects of untreated PPD. PMID- 26276423 TI - Components of a TIP Model Program. AB - Transition-aged youth in need of services and supports find themselves in a quandary; in certain instances, they are considered children, whereas in other circumstances, they qualify as adults. Transition to Independence Process (TIP) provides a promising model for transition-aged youth programs. It is distinguished by an emphasis upon client-driven goals, as opposed to agency defined goals. Another key feature is reliance upon collaboration among service providers in order to address the myriad of needs of young adults. From the perspective of transition-aged clients, an efficacious TIP program must offer support services, including mental health care. It must encourage natural supports, including family. All of the facets of a TIP model program should have as their ultimate focus the education and employment of transition-aged youth. Together, these contribute to the best possible outcomes for transition-aged youth. PMID- 26276424 TI - Repeat computed tomography scans after pediatric trauma: results of an institutional effort to minimize radiation exposure. AB - BACKGROUND: Many pediatric trauma patients are initially evaluated at non pediatric, non-trauma centers where they undergo CT prior to transfer to a pediatric trauma center. The purpose of this study is to quantify the number of repeat CT and assess the risk of delayed or missed injuries. METHODS: The institutional pediatric trauma registry was queried for patients evaluated from January 2001 to March 2012. All patients who underwent repeat CT within 24 h after transfer were included. General admission, demographic, and outcome data were analyzed. RESULTS: A total of 6041 patients were transferred from a referring hospital after undergoing CT scans. Five percent of patients underwent repeat CT with a mean age of 6.3 +/- 5.7 years. Patients who underwent repeat CT scans had significantly higher Injury Severity Scores and lower Glasgow Coma Scale. CT head was the most commonly repeated. Comparing results of referring CT scans to repeated scans, there was good agreement between results for head CT (kappa = 0.69) and moderate agreement for abdominopelvic CT (kappa = 0.59). The overall incidence of delayed diagnosis of injuries was 0.7%. CONCLUSION: The low incidence of missed or delayed injuries justifies limiting additional radiation exposure to pediatric trauma patients based on clinical status. PMID- 26276425 TI - Thoracoscopic pleural clipping for the management of congenital chylothorax. AB - PURPOSE: Medical management of congenital chylothoraces consists of total parental nutrition and tube thoracostomy. However, these infants are exposed to significant fluid shifts and the related leukopenia carries a high infection risk. The purpose of this review is to describe the technique of parietal pleural clipping as a surgical treatment of congenital chylothorax. METHODS: The medical records of all patients with a chylothorax diagnosis during the study period of January 2002 to April 2014 were retrospectively reviewed. RESULTS: Six of 14 infants identified underwent thoracoscopic parietal pleural clipping to disrupt the pleural lymphatic channel flow as visualization of the thoracic duct and lymphatics was not possible. Nearly all surgical patients had bilateral disease (5/6). Resolution of chylous leakage was dramatic following parietal clipping. In the surgical patients, chest tube output 2 days prior to surgery averaged 86.96 ml/kg/day. After parietal clipping, chest tube output dropped to an average of 6.5 ml/kg/day on post op day 2. Thereafter, chest tube output remained low to negligible and chest tubes were removed variably as enteral feeds were started. CONCLUSIONS: We describe a straightforward technique of thoracoscopic parietal pleural clipping as a safe and successful option for treatment of congenital chylothoraces. PMID- 26276426 TI - Rho-kinase expression in Hirschsprung's disease. AB - BACKGROUND: Rho-kinase (ROCK) is the primary effector protein in the RhoA pathway, which regulates Ca(2+)-independent smooth muscle contraction in the human bowel. This pathway has been reported to be hyper-activated in the aganglionic bowel of EDNRB-null (-/-) rats compared to the ganglionic bowel from EDNRB (+/+) rats. We hypothesised that ROCK expression is up-regulated in human aganglionic bowel and designed this study to investigate ROCK 1 and ROCK 2 expression in Hirschsprung's disease (HSCR) and controls. MATERIALS AND METHODS: Full-length specimens were collected following pull-through surgery for HSCR (n = 9). Colonic controls (n = 6) were obtained during colostomy closure from patients with anorectal malformations. Distribution of ROCK 1/2 expression was evaluated using double-labelled immunofluorescence and confocal microscopy. ROCK1/2 protein expression was assessed in mucosa and tunica muscularis using western blot analysis. RESULTS: There was strong expression of both ROCK 1 and ROCK 2 in interstitial cells of Cajal (ICCs) and ganglia. ROCK 1 expression was reduced in aganglionic bowel compared to HSCR ganglionic bowel and controls in both mucosa and tunica muscularis. ROCK 2 expression was similar in the colon of children with HSCR and controls. CONCLUSIONS: This is the first report of strong ROCK expression in colonic ICCs. Although the rat model of aganglionic bowel suggests that Ca(2+)-independent smooth muscle contraction involving ROCK is hyper activated, our data indicate ROCK 1 expression is decreased in aganglionic bowel and ROCK 2 expression is unaltered in children with HSCR. PMID- 26276427 TI - Causal relationship between delayed gastric emptying and gastroesophageal reflux in patients with neurological impairment. AB - PURPOSE: To investigate the causal relationship between delayed gastric emptying (DGE) and gastroesophageal reflux (GER) in patients with neurological impairment (NI). METHODS: Subjects included 30 NI patients (age, 1-34 years; median, 6 years). Combined multichannel intraluminal impedance-pH (MII-pH) monitoring and (13)C-breath test evaluated acid/non-acid reflux episodes (RE) and gastric emptying rates, respectively. Values are shown with medians and ranges. RESULTS: Percentage time for esophageal pH < 4.0 (reflux index: RI) and numbers for total RE and RE > 5 min were 8.3 (0-35.7), 44 (0-129), and 5 (0-22), respectively. Total percentage time and bolus RE numbers were 1.4 (0.0-6.9) and 49 (2-159), respectively. Median bolus clearance time was 16 s (9-45). T 1/2, T lag, and GEC were 103 s (75-204), 54 s (18-97), and 3.4 (2.3-4.3), respectively. Gastric emptying rates and acid/non-acid reflux parameters were not significantly correlated, except T 1/2 correlated significantly with the numbers of RE > 5 min (p = 0.04). T 1/2 inversely correlated with bolus clearance time (p = 0.01). Reflux parameters between DGE and non-DGE patients were not significantly different, except median bolus clearance time was significantly shorter in DGE patients (p = 0.01). CONCLUSIONS: NI patients showed a wide range of gastric emptying rates without any significant causal relationship between DGE and GER. PMID- 26276428 TI - Impact of an external lengthening procedure on the outcome of long-gap esophageal atresia at our hospitals. AB - PURPOSE: To demonstrate the outcome of external lengthening for long-gap esophageal atresia (LGEA) at our hospitals. METHODS: Five patients with LGEA underwent external lengthening between 2010 and 2014 (group A), and 11 patients with LGEA underwent other lengthening techniques between 1990 and 2011 (group B). We compared the procedure and outcome between these two groups. RESULTS: The mean birth weight was 2001 g in group A and 2485 g in group B (p = 0.06). The mean age at esophageal reconstruction was 28 days in group A and 227 days in group B (p = 0.03). Although primary esophageal anastomosis without myotomy was feasible in all patients in group A, a myotomy was needed for primary esophageal anastomosis in half of the patients in group B. Anastomotic leakage occurred in none in group A and in six patients in group B (p = 0.03). The mean age at the establishment of full oral feeding was 76 days in group A and 686 days in group B (p = 0.009). CONCLUSION: External traction for LGEA can effectively lengthen the esophagus to enable primary anastomosis at an earlier age. This may facilitate oral intake. PMID- 26276429 TI - Surgical closure of the larynx for intractable aspiration pneumonia: cannula-free care and minimizing the risk of developing trachea-innominate artery fistula. AB - There is a risk of developing a fatal trachea-innominate artery fistula following laryngotracheal separation for the prevention of intractable aspiration pneumonia. We developed a novel technique of surgical closure of the larynx to avoid this complication and provide long-term cannula-free care. PMID- 26276430 TI - Phylogenetic and amino acid conservation analyses of bacterial L-aspartate-alpha decarboxylase and of its zymogen-maturation protein reveal a putative interaction domain. AB - BACKGROUND: All organisms must synthesize the enzymatic cofactor coenzyme A (CoA) from the precursor pantothenate. Most bacteria can synthesize pantothenate de novo by the condensation of pantoate and beta-alanine. The synthesis of beta alanine is catalyzed by L-aspartate-alpha-decarboxylase (PanD), a pyruvoyl enzyme that is initially synthesized as a zymogen (pro-PanD). Active PanD is generated by self-cleavage of pro-PanD at Gly24-Ser25 creating the active-site pyruvoyl moiety. In Salmonella enterica, this cleavage requires PanM, an acetyl-CoA sensor related to the Gcn5-like N-acetyltransferases. PanM does not acetylate pro-PanD, but the recent publication of the three-dimensional crystal structure of the PanM homologue PanZ in complex with the PanD zymogen of Escherichia coli provides validation to our predictions and provides a framework in which to further examine the cleavage mechanism. In contrast, PanD from bacteria lacking PanM efficiently cleaved in the absence of PanM in vivo. RESULTS: Using phylogenetic analyses combined with in vivo phenotypic investigations, we showed that two classes of bacterial L-aspartate-alpha-decarboxylases exist. This classification is based on their posttranslational activation by self-cleavage of its zymogen. Class I L-aspartate-alpha-decarboxylase zymogens require the acetyl-CoA sensor PanM to be cleaved into active PanD. This class is found exclusively in the Gammaproteobacteria. Class II L-aspartate-alpha-decarboxylase zymogens self cleave efficiently in the absence of PanM, and are found in a wide number of bacterial phyla. Several members of the Euryarchaeota and Crenarchaeota also contain Class II L-aspartate-alpha-decarboxylases. Phylogenetic and amino acid conservation analyses of PanM revealed a conserved region of PanM distinct from conserved regions found in related Gcn5-related acetyltransferase enzymes (Pfam00583). This conserved region represents a putative domain for interactions with L-aspartate-alpha-decarboxylase zymogens. This work may inform future biochemical and structural studies of pro-PanD-PanM interactions. CONCLUSIONS: Experimental results indicate that S. enterica and C. glutamicum L-aspartate alpha-decarboxylases represent two different classes of homologues of these enzymes. Class I homologues require PanM for activation, while Class II self cleave in the absence of PanM. Computer modeling of conserved amino acids using structure coordinates of PanM and L-aspartate-alpha-decarboxylase available in the protein data bank (RCSB PDB) revealed a putative site of interactions, which may help generate models to help understand the molecular details of the self cleavage mechanism of L-aspartate-alpha-decarboxylases. PMID- 26276432 TI - Discovery of potent HIV-1 non-nucleoside reverse transcriptase inhibitors from arylthioacetanilide structural motif. AB - The poor pharmacokinetics, side effects and particularly the rapid emergence of drug resistance compromise the efficiency of the clinically used anti-HIV drugs. Therefore, the discovery of novel and effective NNRTIs is still an extremely primary mission. Arylthioacetanilide family is one of the highly active HIV-1 NNRTIs against wide-type (WT) HIV-1 and a wide range of drug-resistant mutant strains. Especially, VRX-480773 and RDEA806 have been chosen as candidates for further clinical studies. In this article, we review the discovery and development of the arylthioacetanilides, and, especially, pay much attention to the structural modifications, SARs conclusions and molecular modeling. Moreover, several medicinal chemistry strategies to overcome drug resistance involved in the optimization process of arylthioacetanilides are highlighted, providing valuable clues for further investigations. PMID- 26276433 TI - Antitumor activity of endoperoxide-iron chelator conjugates-design, synthesis and biological evaluation. AB - The effort to pursue effective anti-cancer drugs with novel mechanism of action has been continued for decades. As an antimalarial agent, artemisinin is well known for its endoperoxide moiety, which is activated by the cellular iron. Meanwhile, the anti-cancer activity of artemisinin is recognized and reported. Herein, we report on the design, synthesis and evaluation of a series of endoperoxide and iron chelating moiety conjugates. Our study demonstrated that the endoperoxide-quinoline conjugates displayed effective antiproliferative capability and good selectivity against certain cancer cells, while both hydroxamate and catechol-endoperoxide conjugates shown no significant inhibitory activity. Preliminary mechanism investigation suggested that the antiproliferative activity of these conjugates is related to the endoperoxide moiety as well as their iron-chelating ability. These compounds are expected to be used as prototype for further development of selective anti-cancer drug candidate. PMID- 26276431 TI - Ultrastructural markers of quality are impaired in human metaphase II aged oocytes: a comparison between reproductive and in vitro aging. AB - PURPOSE: Childbearing delay contributes to the increase of subfertile couples that require assisted reproductive technology (ART). Subfertility relates with reproductive aging (RA). In vitro aging (IvA) (due to extended culture) may also impair oocyte competence. Aims of this study were to evaluate and compare the oocyte ultrastructure after RA and IvA. METHODS: Cumulus-oocyte complexes (COCs) (n = 68), with metaphase II oocyte and expanded cumulus, from consenting patients (<35 years old and >=35 years old, n = 36), were selected by phase contrast microscopy and fixed at pick up, or after 24 h culture. COCs (n = 44) were studied by light and qualitative/morphometric transmission electron microscopy. Two-way ANOVA, with age and culture as grouping factors, was applied for statistical analysis (p < 0.05). Metaphase II cumulus-free oocytes (n = 24) were selected for confocal microscopy observations. RESULTS: Significant decrease of mitochondria-smooth endoplasmic reticulum aggregates, increase of mitochondria vesicle complexes size and amount, decrease of cortical granules and microvilli, and alterations of the spindle structure characterized both RA and IvA oocytes. These changes were significantly more evident in the RA oocytes submitted to IvA. RA oocytes also showed changes of the zona pellucida and occurrence of vacuoles after culture. Cumuli appeared re-compacted after culture, irrespective of the age of the patients. CONCLUSIONS: These data demonstrated that aging is related to decay of oocyte ultrastructural quality, and that oocytes from elder women are more sensitive to prolonged culture (IvA) than the oocytes from younger women. These morphological results should be considered when applying ART in aged patients, rescue ICSI, or artificial oocyte activation. PMID- 26276434 TI - Recent advances on the synthesis of hepatitis C virus NS5B RNA-dependent RNA polymerase inhibitors. AB - Hepatitis C is a viral liver infection considered as the major cause of cirrhosis and hepatocellular carcinoma (HCC). The HCV NS5B polymerase, an RNA-dependent RNA polymerase, is essential for HCV replication, which is able to catalyze the synthesis of positive (genomic) and negative (template) strand HCV RNA, but has no functional equivalent in mammalian cells. Therefore, the NS5B polymerase has emerged as an attractive target for the development of specifically targeted antiviral therapy for HCV (DAA, for direct-acting antivirals). Recently, a growing number of compounds have been reported as the NS5B polymerase inhibitors, some of which especially have been licensed in clinical trials. This review describes recent advances on the synthesis of the NS5B polymerase inhibitors, focusing on the merits and demerits of their synthetic methods. In particular, inspiration from the synthesis and the future direction of the NS5B polymerase inhibitors are highlighted. PMID- 26276435 TI - Pyrimidine sulfonylacetanilides with improved potency against key mutant viruses of HIV-1 by specific targeting of a highly conserved residue. AB - Based on molecular simulation, the etravirine-VRX-480773 hybrids previously disclosed by our group were optimized to yield novel pyrimidine sulfonylacetanilides 8 with improved activity against a panel of seven clinically relevant single and double mutant strains of HIV-1. The improvement in potency in this in vitro model of HIV RNA replication partly validates the mechanism by which this class of allosteric pyrimidine derivatives inhibits the reverse transcriptase (RT), and represents a remarkable step forward in the development of anti-HIV drugs. PMID- 26276436 TI - Carbonic anhydrase inhibitors: Design, synthesis and structural characterization of new heteroaryl-N-carbonylbenzenesulfonamides targeting druggable human carbonic anhydrase isoforms. AB - A set of heteroaryl-N-carbonylbenzenesulfonamides has been designed, synthesized, and screened as inhibitors of human carbonic anhydrases (hCAs). The new sulfonamide derivatives were tested against hCA I, hCA II, hCA VII, hCA IX, and hCA XII isoforms using acetazolamide (AAZ, 1) and topiramate (TPM, 2) as reference compounds. Six compounds were low nanomolar inhibitors of tumor associated hCA IX isoform (Ki values < 10 nM); among them we identified three arylsulfonamides showing unexpected inefficacy over brain distributed hCA VII isoform (hCA IX/hCA VII selectivity ratio > 1500 for compound 5c). Thus, these compounds can offer the opportunity to highlight the interactions preventing the inhibition of hCA VII mainly expressed in central nervous system. Thereby, we used structural and computational techniques to study in depth the interaction with hCAs. In an effort to confirm the inhibitory action we determined crystal structures of five selected heteroaryl-N-carbonylbenzenesulfonamides (4a, 4b, 4e, 5c, and 5e) in complex with hCA II. Moreover, to explore the lack of inhibitory effects of selected compounds (e.g.4b and 5c) we also performed docking studies into hCA VII catalytic site. PMID- 26276437 TI - Thiazole compounds with activity against Cryptococcus gattii and Cryptococcus neoformans in vitro. AB - Human cryptococcosis can occur as a primary or opportunistic infection and develop as an acute, subacute, or chronic, systemic infection involving different host organs. We evaluated the antifungal activity of thirteen compounds against Cryptococcus gattii and Cryptococcus neoformans in vitro, by assessing the toxicity of the compounds showing the greatest antifungal activity in VERO cells and murine macrophages. From these results, four compounds were considered promising for further studies because they displayed low cytotoxicity and significant antifungal activity. The heterocyclic compounds 1b, 1c, 1d, and 1m have antifungal activity levels between that of amphotericin B and fluconazole in vitro. The death curve of Cryptococcus spp. treated with these four compounds was similar to the curve obtained for amphotericin B, in that we observed a significant reduction in cell viability within the first 24 h of treatment. Additionally, we found that there was no effect when these compounds were combined with amphotericin and fluconazole, except for 1c, which antagonized the effect of amphotericin B against C. gattii, also reflected in the reduction of the post-antifungal effect (PAFE); however, this interaction did not alter the ergosterol content. The results shown in this paper reveal the discovery of novel thiazole compounds, which are easy to synthesize, and with potentially exhibit antifungal activity, and display low cytotoxicity in normal mammalian cells. These compounds can be used as prototypes for the design of new antifungal drugs against C. gattii and C. neoformans. PMID- 26276438 TI - Perceived ethnic discrimination, acculturation, and psychological distress in women of Turkish origin in Germany. AB - PURPOSE: Discrimination is linked to various health problems, including mental disorders like depression and also has a negative effect on the access to mental health care services. Little is known about factors mitigating the association between ethnic discrimination and mental distress. METHODS: The present study examined the extent of the relationship between perceived ethnic discrimination and psychological distress among women of Turkish origin residing in Berlin, and explored whether this association is moderated by acculturation strategies while controlling for known predictors of distress in migrant populations. RESULTS: A total of 205 women of Turkish origin participated in the study. 55.1% of the participants reported some degree of ethnic discrimination. The degree of reported discrimination varied according to acculturation. The highest level of ethnic discrimination was found in the second generation separated group and both generations of the marginalized group. Further, the results indicate an association between ethnic discrimination and distress while adjusting for known socio-demographic predictors of distress, migration-related factors, and neuroticism (B = 5.56, 95% CI 2.44-8.68, p < 0.001). However, the relationship did vary as a function of acculturation strategy, showing an association only in the separated group. CONCLUSIONS: The findings highlight the effects of ethnic discrimination beyond the influence of known risk factor for psychological distress in migrants, such as unemployment, being single, having a limited residence permit or the presence of personality structures that may increase vulnerability for stress responses and mental disorders. PMID- 26276439 TI - Gene regulation of filaggrin and other skin barrier proteins via aryl hydrocarbon receptor. AB - Aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that binds to structurally diverse chemicals including dioxins, coal tar, flavonoids and tryptophan photoproducts. Upon ligation, cytoplasmic AHR translocates to the nucleus, heterodimerizes with aryl hydrocarbon receptor nuclear translocator and mediates numerous biological effects by inducing the transcription of various AHR responsive genes such as epidermal barrier proteins. The activation of AHR usually generates oxidative stress. However, AHR also mediates antioxidant signaling by a plethora of ligands via nuclear factor-erythroid 2-related factor 2. Both oxidative and antioxidant ligands upregulate the expression of the filaggrin gene. We review the role of AHR signaling in the gene regulation of epidermal barrier proteins. PMID- 26276440 TI - Understanding age-induced alterations to the biomechanical barrier function of human stratum corneum. AB - BACKGROUND: The appearance and function of human skin are dramatically altered with aging, resulting in higher rates of severe xerosis and other skin complaints. The outermost layer of the epidermis, the stratum corneum (SC), is responsible for the biomechanical barrier function of skin and is also adversely transformed with age. With age the keratin filaments within the corneocytes are prone to crosslinking, the amount of intercellular lipids decreases resulting in fewer lipid bilayers, and the rate of corneocyte turnover decreases. OBJECTIVES: The effect of these structural changes on the mechanical properties of the SC has not been determined. Here we determine how several aspects of the SC's mechanical properties are dramatically degraded with age. METHODS: We performed a range of biomechanical experiments, including micro-tension, bulge, double cantilever beam, and substrate curvature testing on abdominal stratum corneum from cadaveric female donors ranging in age from 29 to 93 years old. RESULTS: We found that the SC stiffens with age, indicating that the keratin fibers stiffen, similarly to collagen fibers in the dermis. The cellular cohesion also increases with age, a result of the altered intercellular lipid structure. The kinetics of water movement through the SC is also decreased. CONCLUSIONS: Our results indicate that the combination of structural and mechanical property changes that occur with age are quite significant and may contribute to the prevalence of skin disorders among the elderly. PMID- 26276441 TI - Effects of adalimumab, etanercept and ustekinumab on the expression of psoriasin (S100A7) in psoriatic skin. AB - BACKGROUND: Psoriasis is a chronic inflammatory skin disease. It is characterized by immune cell activation and altered epidermal differentiation. S100A7 (psoriasin) is overexpressed in psoriasis, suggesting a determinant role of this protein in inflammation and keratinocyte differentiation. OBJECTIVE: The purpose of this study was to investigate the expression of S100A7 in the skin from psoriatic patients undergoing biological therapy with adalimumab, etanercept or ustekinumab. METHODS: S100A7 expression and distribution were analyzed by immunohistochemistry. RESULTS: S100A7, overexpressed in epidermal keratinocytes of psoriatic lesions, was downregulated, under the biological therapy with adalimumab, etanercept or ustekinumab, only in patients achieving a PASI score<15. CONCLUSIONS: Dysregulation of S100A7 may represent a non-negligible player in the maintenance of psoriasis and the relative epidermal changes. Blockage of S100A7 may represent an additional therapeutic approach in the treatment of psoriasis. PMID- 26276442 TI - Detection of serum neutralizing antibodies to Simbu sero-group viruses in cattle in Tanzania. AB - BACKGROUND: Orthobunyaviruses belonging to the Simbu sero-group occur worldwide, including the newly recognized Schmallenberg virus (SBV) in Europe. These viruses cause congenital malformations and reproductive losses in ruminants. Information on the presence of these viruses in Africa is scarce and the origin of SBV is unknown. The aim of this study was to investigate the presence of antibodies against SBV and closely related viruses in cattle in Tanzania, and their possible association with reproductive disorders. RESULTS: In a cross-sectional study, serum from 659 cattle from 202 herds collected in 2012/2013 were analyzed using a commercial kit for SBV ELISA, and 61 % were positive. Univariable logistic regression revealed significant association between ELISA seropositivity and reproductive disorders (OR = 1.9). Sera from the same area collected in 2008/2009, before the SBV epidemic in Europe, were also tested and 71 (54.6 %) of 130 were positive. To interpret the ELISA results, SBV virus neutralization test (VNT) was performed on 110 sera collected in 2012/2013, of which 51 % were positive. Of 71 sera from 2008/2009, 21 % were positive. To investigate potential cross reactivity with related viruses, 45 sera from 2012/2013 that were positive in SBV ELISA were analyzed in VNTs for Aino, Akabane, Douglas, Peaton, Sabo, SBV, Sathuperi, Shamonda, Simbu and Tinaroo viruses. All 45 sera were positive for one or more of these viruses. Twenty-nine sera (64.4 %) were positive for SBV, and one had the highest titer for this virus. CONCLUSIONS: This is the first indication that Aino, Akabane, Douglas, Peaton, Sabo, SBV, Sathuperi, Shamonda and Tinaroo viruses circulate and cause negative effect on reproductive performance in cattle in Tanzania. SBV or a closely related virus was present before the European epidemic. However, potential cross reactivity complicates the interpretation of serological studies in areas where several related viruses may circulate. Virus isolation and molecular characterization in cattle and/or vectors is recommended to further identify the viruses circulating in this region. However, isolation in cattle is difficult due to short viremic period of 2 to 6 days, and isolation in vectors does not necessarily reflect the situation in cattle. PMID- 26276444 TI - Cloning and Expression of Plantaricin W Produced by Lactobacillus plantarum U10 Isolate from "Tempoyak" Indonesian Fermented Food as Immunity Protein in Lactococcus lactis. AB - Plantaricins, one of bacteriocin produced by Lactobacillus plantarum, are already known to have activities against several pathogenic bacterium. L. plantarum U10 isolated from "tempoyak," an Indonesian fermented food, produced one kind of plantaricin designated as plantaricin W (plnW). The plnW is suggested as a putative membrane location of protein and has similar conserved motif which is important as immunity to bacteriocin itself. Thus, due to study about this plantaricin, several constructs have been cloned and protein was analyzed in Lactococcus lactis. In this study, plnW gene was successfully cloned into vector NICE system pNZ8148 and created the transformant named L. lactis NZ3900 pNZ8148 WU10. PlnW protein was 25.3 kDa in size. The concentration of expressed protein was significantly increased by 10 ng/mL nisin induction. Furthermore, PlnW exhibited protease activity with value of 2.22 +/- 0.05 U/mL and specific activity about 1.65 +/- 0.03 U/mg protein with 50 ng/mL nisin induction. Immunity study showed that the PlnW had immunity activity especially against plantaricin and rendered L. lactis recombinant an immunity broadly to other bacteriocins such as pediocin, fermentcin, and acidocin. PMID- 26276443 TI - Health system context and implementation of evidence-based practices-development and validation of the Context Assessment for Community Health (COACH) tool for low- and middle-income settings. AB - BACKGROUND: The gap between what is known and what is practiced results in health service users not benefitting from advances in healthcare, and in unnecessary costs. A supportive context is considered a key element for successful implementation of evidence-based practices (EBP). There were no tools available for the systematic mapping of aspects of organizational context influencing the implementation of EBPs in low- and middle-income countries (LMICs). Thus, this project aimed to develop and psychometrically validate a tool for this purpose. METHODS: The development of the Context Assessment for Community Health (COACH) tool was premised on the context dimension in the Promoting Action on Research Implementation in Health Services framework, and is a derivative product of the Alberta Context Tool. Its development was undertaken in Bangladesh, Vietnam, Uganda, South Africa and Nicaragua in six phases: (1) defining dimensions and draft tool development, (2) content validity amongst in-country expert panels, (3) content validity amongst international experts, (4) response process validity, (5) translation and (6) evaluation of psychometric properties amongst 690 health workers in the five countries. RESULTS: The tool was validated for use amongst physicians, nurse/midwives and community health workers. The six phases of development resulted in a good fit between the theoretical dimensions of the COACH tool and its psychometric properties. The tool has 49 items measuring eight aspects of context: Resources, Community engagement, Commitment to work, Informal payment, Leadership, Work culture, Monitoring services for action and Sources of knowledge. CONCLUSIONS: Aspects of organizational context that were identified as influencing the implementation of EBPs in high-income settings were also found to be relevant in LMICs. However, there were additional aspects of context of relevance in LMICs specifically Resources, Community engagement, Commitment to work and Informal payment. Use of the COACH tool will allow for systematic description of the local healthcare context prior implementing healthcare interventions to allow for tailoring implementation strategies or as part of the evaluation of implementing healthcare interventions and thus allow for deeper insights into the process of implementing EBPs in LMICs. PMID- 26276445 TI - Advanced Glycation-Modified Human Serum Albumin Evokes Alterations in Membrane and Eryptosis in Erythrocytes. AB - Increased burden of advanced glycation end-products (AGEs) in case of hyperglycemic conditions leads to the development of retinopathy, nephropathy, and cardiovascular and neurological disorders such as Alzheimer's disease. AGEs are considered as pro-oxidants, and their accumulation increases the oxidative stress. The prolonged exposure to these AGEs is the fundamental cause of chronic oxidative stress. Abnormal morphology of red blood cells (RBCs) and excessive eryptosis has been observed in diabetes, glomerulonephritis, dyslipidemia, and obesity, but yet the contribution of extracellular AGEs remains undefined. In this study, we investigated the effect of AGEs on erythrocytes to determine their impact on the occurrence of different pathological forms of these blood cells. Specifically, carboxymethyllysine (CML), carboxyethyllysine (CEL), and Arg pyrimidine (Arg-P) which have been reported to be the most pre-dominant AGEs formed under in vivo conditions were used in this study. Results suggested the eryptotic properties of CML, CEL, and Arg-P for RBCs, which were evident from the highly damaged cell membrane and occurrence of abnormal morphologies. Methylglyoxal-modified albumin showed more severe effects, which can be attributed to the high reactivity and pro-oxidant nature of glycation end products. These findings suggest the possible role of AGE-modified albumin towards the morphological changes in erythrocyte's membrane associated with diabetic conditions. PMID- 26276446 TI - Molecular Cloning and Characterization of Spermine Synthesis Gene Associated with Cold Tolerance in Tea Plant (Camellia sinensis). AB - Spermine synthase (SPMS, EC 2.5.1.22), enzyme of spermine (Spm) biosynthesis, has been shown to be related to stress response. In this study, attempts were made to clone and characterize a gene encoding SPMS from tea plant (Camellia sinensis). The effect of exogenous application of Spm in C. sinensis subjected to low temperature stress was also investigated. A full-length SPMS complementary DNA (cDNA) (CsSPMS) with an open reading frame of 1113 bp was cloned using reverse transcription-PCR and rapid amplification of cDNA ends (RACE) techniques from cultivar "Yingshuang". The CsSPMS gene, which encoded a 371 amino acid polypeptide, in four cultivars is highly homologous. Quantitative real-time PCR indicated that the CsSPMS gene shows tissue-specific expression, mainly in the leaf and root of tea plant. The expression analysis demonstrated that the CsSPMS gene is quickly induced by cold stress and had similar trends in four cultivars. Spm-supplemented "Baicha" cultivar contains higher endogenous polyamines compared to the control, coupling with higher expression levels of ADC and SPMS. In addition, activities of peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), as well as free proline content in the Spm-supplemented samples were higher than the control during the experiment course or at a given time point, indicating that Spm exerted a positive effect on antioxidant systems. Moreover, Agrobacterium-mediated expression of CsSPMS in tobacco leaves showed relatively higher cold tolerance. Taken together, these findings will enhance the understanding of the relationships among CsSPMS gene regulatory, polyamines accumulation, and cold tolerance in tea plant. PMID- 26276447 TI - Evaluation of smoking-specific and generic quality of life measures in current and former smokers in Germany and the United States. AB - BACKGROUND: Health-related quality of life (QOL) surveys include generic measures that enable comparisons across conditions and measures that focus more specifically on one disease or condition. We evaluated the psychometric properties of German- and English-language versions of survey scales representing both types of measures in samples of current and former smokers. METHODS: TQOLIT(TM)v1 integrates new measures of smoking-specific symptoms and QOL impact attributed to smoking with generic SF-36 Health Survey measures. For purposes of evaluation, cross-sectional data were analyzed for two independent samples. Disease-free (otherwise healthy) adults ages 23-55 used a tablet to complete surveys in a clinical trial in Germany (125 current and 54 former smokers). Online general population surveys were completed in the US by otherwise healthy current and former smokers (N = 149 and 110, respectively). Evaluations included psychometric tests of assumptions underlying scale construction and scoring, score distributions, and reliability. Tests of validity included cross-sectional correlations and analyses of variance based on a conceptual framework and hypotheses for groups differing in self-reported smoking behavior (current versus former smoker, cigarettes per day (CPD)) and severity of smoking symptoms in both samples and, in the German trial only, clinical parameters of biomarkers of exposure. RESULTS: Tests of scaling assumptions and internal consistency reliability (alpha = 0.71-0.79) of the smoking-specific measures were satisfactory, although ceiling effects attenuated correlations for former smokers in both samples. Correlational evidence supporting validity of smoking-specific symptom and impact measures included their substantial inter-correlation and higher correlations (than generic measures) with smoking behavior (favoring former over current groups) and CPD in both samples. In the German trial, both smoking-specific measures correlated significantly (p < 0.05) with all four biomarkers. QOL impact attributed to smoking correlated with the SF-36 mental but not physical summary measures in both samples. CONCLUSIONS: German- and English language TQOLITv1 surveys have comparable and satisfactory psychometric properties. Cross-sectional tests, including correlations with four biomarkers, support the validity of the new smoking-specific measures for use in studies of otherwise healthy smokers. Smoking-specific measures consistently performed better than generic QOL measures in all tests of validity. PMID- 26276448 TI - Evaluating non-disclosure of errors and healthcare organization: a case of bioethics consultation. AB - Sometimes medical errors should not be disclosed. We report a case of semen samples exchange, during a homologous artificial insemination procedure, where a bioethics consultation was required. The bioethics consultation addressed ethical and legal elements in play, supporting non-disclosure to some of the subjects involved. Through a proper methodology, gathering factual and juridical elements, a consultant can show when a moral dilemma between values and rights-privacy versus fatherhood, in our case-is unsubstantial, in a given context, because of the groundlessness of the value or the right itself. However, being the error elicited by organizational factors, a broader ethical pronouncement was needed. Under such circumstances, ethical evaluation should engage in a sort of 'ethical based root-cause analysis', linking ethical principles to quality aims and showing the opportunity to integrate ethical methodology in healthcare management. From this perspective, errors may become an incentive to promote high quality organizations, attending to the central value of person even through the organizational process. PMID- 26276449 TI - Rethinking risk assessment for emerging technology first-in-human trials. AB - Recent progress in synthetic biology (SynBio) has enabled the development of novel therapeutic opportunities for the treatment of human disease. In the near future, first-in-human trials (FIH) will be indicated. FIH trials mark a key milestone in the translation of medical SynBio applications into clinical practice. Fostered by uncertainty of possible adverse events for trial participants, a variety of ethical concerns emerge with regards to SynBio FIH trials, including 'risk' minimization. These concerns are associated with any FIH trial, however, due to the novelty of the approach, they become more pronounced for medical applications of emerging technologies (emTech) like SynBio. To minimize potential harm for trial participants, scholars, guidelines, regulations and policy makers alike suggest using 'risk assessment' as evaluation tool for such trials. Conversely, in the context of emTech FIH trials, we believe it to be at least questionable to contextualize uncertainty of potential adverse events as 'risk' and apply traditional risk assessment methods. Hence, this issue needs to be discussed to enable alterations of the evaluation process before the translational phase of SynBio applications begins. In this paper, we will take the opportunity to start the debate and highlight how a misunderstanding of the concept of risk, and the possibilities and limitations of risk assessment, respectively, might impair decision-making by the relevant regulatory authorities and research ethics committees, and discuss possible solutions to tackle the issue. PMID- 26276450 TI - Enhanced parathyroid hormone levels are associated with left ventricle hypertrophy in very elderly men and women. AB - Serum parathyroid hormone (PTH) has been found to be associated with cardiovascular mortality in the elderly, but little is known about the mechanisms underlying this association. This study investigated the association between PTH and structural and functional changes of the heart and arterial wall in a cohort of very elderly individuals. Healthy individuals aged 80 years or more (n = 90) underwent evaluation of serum PTH, cardiac morphology and function by Doppler echocardiography, endothelium dependent and independent vasodilatation by brachial reactivity, carotid stiffness and intima-media thickness by ultrasound, and coronary calcification by computed tomography. Participants with PTH levels above the median 5.8 pmol/L had higher left ventricular mass index (P = .02), relative wall thickness (P = .02), left atrial volume index (P = .03), and shorter deceleration time of E mitral wave (P = .04). Serum PTH levels (odds ratio, 1.027; P = .032) and systolic blood pressure (odds ratio, 1.032; P = .008) were independently associated with left ventricular hypertrophy. No difference was found between PTH groups in flow- or nitrate-mediated brachial artery dilatation, coronary artery calcification, intima-media thickness, or arterial stiffness. Elevation of serum PTH in the very elderly is associated with concentric left ventricular hypertrophy, but no association with arterial wall structure or function was found in this study. PMID- 26276451 TI - A half-century of studies of growth hormone insensitivity/Laron syndrome: A historical perspective. AB - A growth hormone (GH) dependent substance responsible for sulfate uptake by costal cartilage of hypophysectomized rats, labeled sulfation factor, was reported in 1957. In 1962 the radioimmunoassay for GH was described. The clinical picture of severe GH deficiency but with high serum concentrations of GH was reported in 3 siblings in 1966 and followed by a 1968 report of 22 patients belonging to 14 consanguineous oriental Jewish families in Israel. Defective sulfation factor generation was demonstrated in 15 of these individuals and in a 1971 report; FFA response to IV GH and growth response to GH injections suggested competitive saturation of peripheral tissue receptors by an abnormal GH. However, studies published in 1973 demonstrated normal fractionation of their circulating GH, and normal binding of GH from 22 patients to various antisera used for radioimmunoassay. In 1976, the Israeli investigators reported that circulating GH from 7 patients reacted normally in the recently developed radioreceptor assay for GH. In 1984, using hepatic microsome pellets, they demonstrated that the defect was a failure of GH binding to receptors. Characterization of the human GH receptor (GHR) gene, reported in 1989, included the initial description of a genetic defect of the GHR in 2 of 9 Israeli patients. At about the same time began the identification in Ecuador of what was to become the largest population of GH insensitivity in the world, ~100 individuals, and the only substantial population with a common mutation of the GH receptor. Treatment studies with recombinant IGF-I began in 1990. Growth response was modest compared to that of GH treated GH deficient subjects. The spectrum of GH insensitivity has expanded beyond GH receptor deficiency to include postreceptor abnormalities: IGF-I gene mutation (1996); IGF-I receptor mutation (2003); signal transducer and activator of transcription 5b mutation (2003); and mutation of the GH-dependent acid labile subunit (2004). CONCLUSION: Rare conditions of GH insensitivity caused by GH receptor and postreceptor abnormalities have provided insights into the processes of growth, body composition, and metabolism. PMID- 26276452 TI - Biolite: A Patented Ultra-Low-Level Laser-Therapy Device for Treating Musculoskeletal Pain and Associated Impairments. AB - After an excursus on state-of-the-art knowledge for low-level laser therapy (LLLT), Biolite, a patented ultra-low-level laser therapy device used to treat musculoskeletal pain and associated impairments, is presented. The application protocols include short stimulation of sequences of acupuncture points. The observed effects seem, however, to be far from those that might be expected after acupuncture. The primary effect seems more likely to be an extracellular soft tissue matrix reaction. The development of the technique, the studies performed, and the evidence collected over > 10 years suggest that specifically modulated laser light can interact with human tissues at light fluences well under those previously considered as being capable of having any effect. Musculoskeletal pain very often becomes an autonomous dysfunction that is independent of the original injury and that can be effectively treated using specific peripheral acupuncture like stimulation. Because such acupuncture is capable of reducing motor control "interferences" from noxious stimuli, it can improve motor control performance, thereby reducing the risk of falls in the elderly individuals. The proposal of acupuncture-derived protocols to be applied by Western physiotherapists using an ultra-low-level laser therapy device is a further "bridge" between two different, and sometimes very different, clinical worlds to better serve our patients. PMID- 26276453 TI - Acupuncture Suppresses Morphine Craving in Progressive Ratio Through the GABA System. AB - Previous studies revealed that acupuncture suppressed both morphine self administration and morphine-seeking behavior after abstinence. Based on these results, this study examined whether acupuncture attenuated morphine-craving under a progressive ratio (PR) schedule and investigated the possible neuronal mechanism. Male Sprague-Dawley rats were trained to self-administer morphine (0.5 mg/kg) at a fixed ratio for 9 days, and rats who achieved stable infusion were switched to a PR schedule. When animals had taken no more morphine for 1 hour, the number of infusions was defined as the break point (BP). After PR training, animals that had established a stable BP received acupuncture the next day. Acupuncture was applied for 1 minute immediately before the test session. Bicuculline (1.0 mg/kg) and SCH 50911 (2.0 mg/kg) were given 30 minutes prior to acupuncture. The c-Fos levels in the ventral tegmental area (VTA) and the nucleus accumbens (NAc) were examined. Acupuncture at SI5 reduced the BP significantly. Moreover, the effects of acupuncture were blocked by either bicuculline or SCH 50911. Immunofluorescence revealed that acupuncture at SI5 decreased c-Fos expressions in the VTA and the NAc. This study demonstrates that acupuncture at SI5 is effective for the treatment of morphine-craving and that this effect is mediated via the GABA pathway. PMID- 26276454 TI - Laser Acupuncture Improves Behavioral Disorders and Brain Oxidative Stress Status in the Valproic Acid Rat Model of Autism. AB - The therapeutic strategy against autism, a severe neurological development disorder, is one of the challenges of this decade. Recent findings show that oxidative stress plays a crucial role on the pathophysiology of autism, and laser acupuncture at Shenmen (HT7) can improve oxidative status in many neurological disorders. Therefore, we aimed to assess the effect of laser acupuncture at HT7 on behavior disorders and oxidative stress status in the cortex, striatum, and hippocampus of the valproic acid rat model of autism. Laser acupuncture was performed once daily during postnatal day (PND) 14-PND 40. Behavioral tests including rotarod, open-field, learning and memory, and social behavior tests were performed during PND 14-PND 40. At the end of study, brain oxidative status including malondialdehyde levels and the activities of superoxide dismutase, catalase, and glutathione peroxidase were determined in the cortex, striatum, and hippocampus. Laser acupuncture at HT7 significantly improved autistic-like behaviors. Decreased malondialdehyde levels were observed in all areas mentioned above, however, increased glutathione peroxidase activity was observed only in the striatum and hippocampus. No changes in superoxide dismutase and catalase activities were observed in any investigated area of the brain. Therefore, our study suggests that laser acupuncture at HT7 partly mitigates autistic-like symptoms via improved oxidative status. PMID- 26276456 TI - Acupressure Bead in the Eustachian Tube. AB - In this article, we aim to enlighten practitioners and patients involved with acupressure beads and to contribute to their safer use by reporting a unique case of insidious intrusion of an acupressure bead into the eustachian tube. A metallic object was found in the eustachian tube of a patient while conducting a magnetic resonance imaging (MRI) examination. The object was later confirmed to be an auricular acupressure bead, and was successfully removed by performing a tympanoplasty and a canal wall down mastoidectomy. The bead was assumed to have passed through an existing perforation of the tympanic membrane. According to previously published literature, tympanic membrane perforations exist in ~1% of the population. Therefore, middle-ear foreign bodies are relatively common occurrences for otolaryngologists. However, metallic objects such as acupressure beads are especially important in the sense that they can cause severe burns during MRI. To avoid potential complications, acupressure-bead practitioners should be aware of the possibility that intrusions through the tympanic membrane could go unnoticed. PMID- 26276455 TI - Could Acupuncture Be Useful in the Treatment of Temporomandibular Dysfunction? AB - In this study, the effects of acupuncture in comparison with flat occlusal plane appliance were evaluated in patient with myogenic temporomandibular dysfunction (TMD). The sample consisted of 40 women with TMD and unbalanced energy predominance of Yang Liver Ascension, selected using the Renying and Cunkou pulses, randomly divided into two groups: acupuncture and splint. The effect of treatments on the masseter and anterior temporal muscles was evaluated after 4 weeks of treatment, by means of electromyographic activity (root mean square) and pain pressure threshold. Pain intensity was measured using the visual analog scale, and range of mouth opening was evaluated using a millimeter ruler. All evaluations were performed at the beginning and end of the treatment. Visual analog scale score was reduced equally in the two groups (p < 0001), and the increase in range of mouth opening was significant in both groups. A significant difference was detected only in pain pressure threshold of the left masseter in the acupuncture group (p < 0.05). Only root mean square in the at rest position of the right temporal muscle diminished in the final stage of the splint group (p < 0.05). Both treatments reduced the pain intensity of myogenic TMD in the short term and may be considered strategies for control of chronic pain related to TMD. PMID- 26276457 TI - Perception of Therapeutic Qi, a Nonmechanical, Nonpsychological Factor in Acupuncture That Originates from the Therapist. AB - So far, most research attempts to explain the mechanism of the action of acupuncture have focused mostly on mechanically-triggered active factors and have produced inconclusive findings. In this study, we investigate whether acupuncture might also involve nonmechanical, nonpsychological active factors originating in the therapist. In 30 individuals, an acupuncture needle was inserted in the acupoint PC6 using a special device without touching the needle. A second device was used to fix the needle rigidly in place, excluding any mechanical transmission of movement from the handle to the needle's tip. Each participant was exposed in random order to a control and a stimulation phase. During the stimulation phase, the free needle's end was held by the therapist to allow the transmission of Qi; during the control phase, it was left untouched. Participants' subjective sensations during the stimulation phase and the control phase were recorded using a questionnaire. Twenty-two of 28 (79%; p = 0.003) test participants believed that they had received stimulation when it had actually been performed, and 26 (93%; p < 0.001) sensed differences between the two experimental phases. Thus, participants were able to sense the transmission of therapeutic Qi in the absence of mechanical or psychological factors. PMID- 26276458 TI - Acupuncture Meridian of Traditional Chinese Medical Science: An Auxiliary Respiratory System. AB - The acupuncture meridian system (AMS) is the key concept of Traditional Chinese Medical Science (TCMS). It is a natural network formed by the tissue space that connects human viscera and skin. In this article, a new hypothesis that the AMS is an auxiliary respiratory system is presented. The AMS collects the CO2 that is produced by tissue supersession and that cannot be excreted via blood circulation, and discharges the CO2 through the body's pores, thus preventing a pressure increase in the internal environment. Thus, local blood circulation will not be blocked, and the body will remain healthy. In addition to neuroregulation and humoral regulation, AMS regulation is an important method of physiological regulation. Furthermore, the pathological principle of the AMS, therapies of TCMS, and the excellent future of the AMS are discussed. PMID- 26276459 TI - Overall State of Pediatric Readiness in U.S. Improved Over the Past 10 Years, but Gaps Remain. PMID- 26276461 TI - Yet another time about time ... Part I: An essay on the phenomenology of physical time. AB - This paper presents yet another personal reflection on one the most important concepts in both science and the humanities: time. This elusive notion has been not only bothering philosophers since Plato and Aristotle. It goes throughout human history embracing all analytical and creative (anthropocentric) disciplines. Time has been a central theme in physical and life sciences, philosophy, psychology, music, art and many more. This theme is known with a vast body of knowledge across different theories and categories. What has been explored concerns its nature (rational, irrational, arational), appearances/qualia, degrees, dimensions and scales of conceptualization (internal, external, fractal, discrete, continuous, mechanical, quantum, local, global, etc.). Of particular interest have been parameters of time such as duration ranges, resolutions, modes (present, now, past, future), varieties of tenses (e.g. present perfect, present progressive, etc.) and some intuitive, but also fancy phenomenological characteristics such as "arrow", "stream", "texture", "width", "depth", "density", even "scent". Perhaps the most distinct characteristic of this fundamental concept is the absolute time constituting the flow of consciousness according to Husserl, the reflection of pure (human) nature without having the distinction between exo and endo. This essay is a personal reflection upon time in modern physics and phenomenological philosophy. PMID- 26276460 TI - Transitioning Adolescents and Young Adults With HIV Infection to Adult Care: Pilot Testing the "Movin' Out" Transitioning Protocol. AB - BACKGROUND: Advances in care and treatment of adolescents/young adults with HIV infection have made survival into adulthood possible, requiring transition to adult care. Researchers have documented that the transition process is challenging for adolescents/young adults. To ensure successful transition, a formal transition protocol is needed. Despite existing research, little quantitative evaluation of the transition process has been conducted. PURPOSE: The purpose of the study was to pilot test the "Movin' Out" Transitioning Protocol, a formalized protocol developed to assist transition to adult care. METHOD: A retrospective medical/nursing record review was conducted with 38 clients enrolled in the "Movin' Out" Transitioning Protocol at a university-based adolescent medicine clinic providing care to adolescents/young adults with HIV infection. RESULTS: Almost half of the participants were able to successfully transition to adult care. Reasons for failure to transition included relocation, attrition, lost to follow-up, and transfer to another adult service. Failure to transition to adult care was not related to adherence issues, X(2) (1, N=38)=2.49, p=.288; substance use, X(2) (1, N=38)=1.71, p=.474; mental health issues, X(2) (1, N=38)=2.23, p=.322; or pregnancy/childrearing, X(2) (1, N=38)=0.00, p=.627). CONCLUSIONS: Despite the small sample size, the "Movin' Out" Transitioning Protocol appears to be useful in guiding the transition process of adolescents/young adults with HIV infection to adult care. More research is needed with a larger sample to fully evaluate the "Movin' Out" Transitioning Protocol. PMID- 26276462 TI - Signs, dispositions, and semiotic scaffolding. AB - In theoretical work we distinguish living beings from inanimate objects on the basis of some paramount attributes, such as agency and autonomy. These abstract features are not directly accessible to our scrutiny, but we surmise their nature through observation of the purpose-oriented behavior of organisms. I intend to show that organismal purposefulness springs from the intrinsic, constitutive kind of finality that is the hallmark of all semiotic transactions. To this aim I develop a dispositionalist account of organismal causation based on a distinction between two kinds of causal dispositions: fixed (efficient) dispositions and traveling dispositions. Fixed dispositions are rigidly attached to physical structures and processes; these are the dispositions regularly invoked in current discussions of causal explanation. Traveling dispositions are able to move freely from one location to another by becoming embodied into suitable supporting media. I introduce these notions to articulate a view of semiosis I deem best suited to the life sciences, and contend that sign tokens are vehicles of traveling dispositions. This account places the origin of purposive behavior at the interaction of physical and semiotic causation. To properly motivate the discussion I briefly review some recent developments in the philosophy of science concerning various forms of causation invoked by scientists across disciplines to frame explanations and make predictions. The ensuing discussion gives particular prominence to mechanistic (as distinct from mechanicist) explanatory accounts of biological phenomena. This review is followed by a brief characterization of a "nomological machine," a comprehensive schema introduced and developed by Nancy Cartwright with the goal of explaining causal mechanisms in a general setting. By capitalizing on this model's heuristic virtues I seek to formulate a compelling view of the interactions between physical and semiotic causation at play in semiotic scaffolding. These interactions transpire between energetic causal chains and a wide range of converging semiotic transactions unfolding within each individual organism and between organisms and their environment. The perspective advanced here helps elucidate the manner in which physical and semiotic causation cooperate in an orchestrated fashion, giving rise to an ever-expanding profusion of scaffolding structures and processes. Using simple examples I outline some mechanisms that bring about this orchestration as well as the resultant channeling activities that eventually merge and find their culmination in the enactment of goal-oriented behavior. PMID- 26276463 TI - Free will: A case study in reconciling phenomenological philosophy with reductionist sciences. AB - Phenomenology aspires to philosophical analysis of humans' subjective experience while it strives to avoid pitfalls of subjectivity. The first step towards naturalizing phenomenology - making phenomenology scientific - is to reconcile phenomenology with modern physics, on the one hand, and with modern cellular and molecular neuroscience, on the other hand. In this paper, free will is chosen for a case study to demonstrate the feasibility. Special attention is paid to maintain analysis with mathematical precision, if possible, and to evade the inherent deceptive power of natural language. Laplace's determinism is re evaluated along with the concept of microscopic reversibility. A simple and transparent version of proof demonstrates that microscopic reversibility is irreconcilably incompatible with macroscopic irreversibility, contrary to Boltzmann's claim. But the verdict also exalts Boltzmann's statistical mechanics to the new height of a genuine paradigm shift, thus cutting the umbilical cord linking it to Newtonian mechanics. Laplace's absolute determinism must then be replaced with a weaker form of causality called quasi-determinism. Biological indeterminism is also affirmed with numerous lines of evidence. The strongest evidence is furnished by ion channel fluctuations, which obey an indeterministic stochastic phenomenological law. Furthermore, quantum indeterminacy is shown to be relevant in biology, contrary to the opinion of Erwin Schrodinger. In reconciling phenomenology of free will with modern sciences, three issues - alternativism, intelligibility and origination - of free will must be accounted for. Alternativism and intelligibility can readily be accounted for by quasi determinism. In order to account for origination of free will, the concept of downward causation must be invoked. However, unlike what is commonly believed, there is no evidence that downward causation can influence, shield off, or overpower low-level physical forces already known to physicists. Quasi determinism offers an escape route: The possibility that downward causation arising from hierarchical organization of biological structures can modify dispersions of physical laws remains open. Empirical evidence in support of downward causation is scanty but nevertheless exists. Still, origination of free will must be considered an unsolved problem at present. It is demonstrated that objectivity does not guarantee scientific rigor in the study of complex phenomena, such as human creativity. In its replacement, universality and overall consistency between a theory and empirical evidence must be maintained. Visual thinking is proposed as a reasoning tool to ensure universality and overall consistency through inference to the best explanation. PMID- 26276464 TI - The quantum epoche. AB - The theme of phenomenology and quantum physics is here tackled by examining some basic interpretational issues in quantum physics. One key issue in quantum theory from the very beginning has been whether it is possible to provide a quantum ontology of particles in motion in the same way as in classical physics, or whether we are restricted to stay within a more limited view of quantum systems, in terms of complementary but mutually exclusive phenomena. In phenomenological terms we could describe the situation by saying that according to the usual interpretation of quantum theory (especially Niels Bohr's), quantum phenomena require a kind of epoche (i.e. a suspension of assumptions about reality at the quantum level). However, there are other interpretations (especially David Bohm's) that seem to re-establish the possibility of a mind-independent ontology at the quantum level. We will show that even such ontological interpretations contain novel, non-classical features, which require them to give a special role to "phenomena" or "appearances", a role not encountered in classical physics. We will conclude that while ontological interpretations of quantum theory are possible, quantum theory implies the need of a certain kind of epoche even for this type of interpretations. While different from the epoche connected to phenomenological description, the "quantum epoche" nevertheless points to a potentially interesting parallel between phenomenology and quantum philosophy. PMID- 26276465 TI - Creation of the relevant next: How living systems capture the power of the adjacent possible through sign use. AB - Stuart Kauffman's revolutionary notion of the Adjacent Possible as an organizing principle in nature shares much in common with logician Charles S. Peirce's understanding of the universe as an ever-unfolding 'process ontology' of possibility space that is brought about through the recursive interaction of genuine possibility, transiently actualized order, and emergent (but never fully deterministic) lawfulness. Proceeding from these three fundamental categories of becoming-as-being, Peirce developed a complimentary logic of sign relations that, along with Estonian biologist Jakob von Uexkull's action-as-meaning-imprinting Umwelt theory, informs the work that is currently being undertaken under the aegis of Biosemiotics. In this paper, I will highlight the deep affinities between Kauffman's notion of the Adjacent Possible and Biosemiotics' hybrid Peircean/Uexkullian "sign" concept, by which living systems - both as individuals and in the aggregate (i.e., as co-actors, communities and lineages) - "capture" relevant aspects of their relations with the immediately given Adjacent Possible and preserve those recipes for future interaction possibilities as biologically instantiated signs. By so doing, living systems move into the Adjacent Possible by "collapsing the wave function" of possibility not just probabilistically, but guided by system-internal values arising from previously captured sign relations that are biologically instantiated as replicable system biases and generative constraints. The influence of such valenced and end-directed action in the world introduces into the universe the phenomenon of the Relevant (and not just deterministic, or even stochastic) Next. My argument in this paper is that organisms live out their lives perpetually confronted with negotiating the omnipresent Relevant Next, and are informed by the biological capture of their (and their lineage's) previous engagements in doing so. And because that "capture" of previous agent-object-action relationships are instantiated as biological signs for the guidance of the organism, not only are "successful survival strategies" within a given possibility space captured (as in traditional accounts of Natural Selection), but captured as well within those signs are the entire complement of previously untaken but still veridical real-world possibility spaces that are inseparably 'entangled' with that sign, and just awaiting exploration by the organism. Thus, while all action in the universe is both current-context dependant and next-context creating, the emergence of ever more complex semiotic capabilities in organisms has expanded the possibility space of immediate-next-action in the world exponentially, and has brought into being not a pre-given, singly end-directed ordered world, but an emergent, many ends-directed world of promiscuous, unforeseeable and interacting telos. The goal of Biosemiotics is to understand and to explore this world. PMID- 26276466 TI - Naturalizing semiotics: The triadic sign of Charles Sanders Peirce as a systems property. AB - The father of pragmatism, Charles Sanders Peirce, gave in 1903 the following definition of a sign: "A Sign, or Representamen, is a First which stands in such a genuine triadic relation to a Second, called its Object, as to be capable of determining a Third, called its Interpretant, to assume the same triadic relation to its Object in which it stands itself to the same Object. The triadic relation is genuine, that is its three members are bound together by it in a way that does not consist in any complexus of dyadic relations". Despite its cult status and its pragmatic foundation, the Peircean sign has never revealed its true potential by being integrated into a formal system. In the present report, a reconstruction of the sign model is presented, which may at first appear somewhat obvious and superficial. However by use of the reconstructed model, the above statement and the majority of Peirce's other statements about the nature of signs fall into place. Instead of defining three links between Object (O), Representamen (R), and Interpretant (I), the sign is described as having a single three-dimensional link, specifying its location in a three dimensional (O,R,I) linkage space. To understand and explain sign function, the process of sign utilization (semiosis) has to be divided into two temporally separated phases, a sign-establishment phase where a three-dimensional link (Psi(O,R,I)) is formed between three sign elements, and a later sign-interpretation phase where the established linkage is used for inferring significance to a novel phenomenon, if this satisfies the criteria for being a Representamen for the sign. Numerous statements from Peirce indicate that he used a two-staged semiosis paradigm although he did not state that explicitly. The three-dimensional model was primarily constructed for use in biosemiotics, as an exploratory frame for mapping the evolutionary establishment of sign links, which logically must have preceded the fixation of any regulatory process in molecular biological systems. It became clear, however, that the model is able to clarify many of the difficult explanations offered by Peirce about his sign model. I make no claim that Peirce used a similar type of three-dimensional model, because he explicitly used the chemical atom as naturalization (natural scientific explanation) for his sign model, an interesting but problematic analogy. In order to discuss common versus specific semiotic scaffolds for molecular biosemiotics, biosemiotics and semiotics proper, I start with a generic definition of the three-dimensional sign system, using human semiosis as examples. After this, the major part of the paper, I define the specific biochemical and evolutionary scaffolds that is used for obtaining the evolutionary memory that is needed for sign establishment. To exemplify semiosis according to the present model I present a typical situation where a Representamen (RE) and an object (OE) in the establishment phase are frequently encountered together by a sign interpreter. The process that links specific Representamens to specific Objects will first involve the recognition of the specific traits that distinguish the two sign elements. Subsequently the establishment process leads to the creation of a specific systems-state, called the Interpretant, which links the two traits in a way that allows retrieval of the information (a memory function). During a later interpretation phase, a hypothetical Object will be inferred by the interpreter when a Representamen (RI) harboring the required characteristics is encountered. This inference happens through a memory retrieval process, irrespective of the fact that relevant Objects of the sign may never be encountered after establishment. A simplified scheme for computer neural network algorithms is introduced as an example of such a system. Since the Peircean sign according to this definition is a systems property, there can be no sign without a sign interpreting systems or without some kind of memory function. A sign interpreter will thus harbor a semiotic scaffold that consists of at least an input sensor and an interpreting system coupled to a memory function. Further border conditions for semiotic scaffolds will be introduced. Peirce published a comprehensive sign definition system, but he allowed only ten sign classes, selected from the twenty-seven sign classes that result from his three main subdivisions, each containing three classes. His allowed sign classes are here identified as those which do not infer more significance during interpretation than was warranted during establishment. The excluded sign classes are either undefinable in his system or are of such a nature that the objects during interpretation are inferred to be much more significant than what was warranted during establishment. Occult signs are of these forbidden free-wheeling types, and it is postulated that they were omitted because Peirce defined his sign classes for use in a novel sign based logical system, where such over-signification would be detrimental. PMID- 26276467 TI - Living science: Science as an activity of living beings. AB - The philosophy of science should accommodate itself to the facts of human existence, using all aspects of human experience to adapt more effectively, as individuals, species, and global ecosystem. This has several implications: (1) Our nature as sentient beings interacting with other sentient beings requires the use of phenomenological methods to investigate consciousness. (2) Our embodied, situated, purposeful physical interactions with the world are the foundation of scientific understanding. (3) Aristotle's four causes are essential for understanding living systems and, in particular, the final cause aids understanding the role of humankind, and especially science, in the global ecosystem. (4) In order to fulfill this role well, scientists need to employ the full panoply of human faculties. These include the consciousness faculties (thinking, sensation, feeling, intuition), and therefore, as advocated by many famous scientists, we should cultivate our aesthetic sense, emotions, imagination, and intuition. Our unconscious faculties include archetypal structures common to all humans, which can guide scientific discovery. By striving to engage the whole of human nature, science will fulfill better its function for humans and the global ecosystem. PMID- 26276468 TI - Brain arteriovenous malformations in elderly patients: clinical features and treatment outcome. AB - BACKGROUND: In this aging society, attention has not been fully given to brain arteriovenous malformations (AVMs) in elderly patients. This study sought to describe a single institution's experience treating arteriovenous malformations (AVMs) in elderly patients. METHODS: We conducted a retrospective review of brain AVMs in elderly patients treated at our institution between 1990 and 2012 with a focus on the clinical features, risk of hemorrhage and treatment outcomes. RESULTS: Of the 2790 patients in our AVM database, 98 patients were over the age of 60 at presentation. Forty-eight percent presented with hemorrhage. Risks of initial hemorrhage were history of hypertension, smaller AVM size (<3 cm) and exclusively deep venous drainage. Treatment modalities were microsurgical resection in 65 %, embolization alone in 10 %, stereotactic radiosurgery (SRS) in 11 % and observation in 14 %. Preoperative embolization was performed in 32 % in the surgical group. Complete obliteration was achieved in 95 % by microsurgery, 30 % by embolization alone and 45 % by SRS. Good functional outcome (modified Rankin Scale, mRS <2) was achieved in 69 % after a median follow-up of 5.8 years. Multivariate logistic analysis revealed that a pretreatment mRS score >=2, eloquent location and higher S-M grade (IV or V) were associated with worsening functional status, whereas surgical resection was a negative factor. Posttreatment hemorrhage occurred in 8 %. AVM-related death occurred in three patients (2 by surgery and 1 by observation). CONCLUSIONS: Brain AVMs in elderly patients still pose a high risk of hemorrhage. Initial hemorrhage may be associated with a history of hypertension, AVM size and exclusively deep venous drainage. Initial mRS score >=2, eloquent location and higher S-M grade may be associated with worsening functional status. Microsurgical resection can be safe and effective for selected patients. Preoperative embolization is helpful in patients with S-M grade IV-V AVMs. For those with surgical contraindications, SRS and observation are treatment alternatives. PMID- 26276469 TI - Bony surface registration of navigation system in the lateral or prone position: technical note. AB - BACKGROUND: Navigation systems have become essential tools in neurosurgery. Precise registration is indispensable for the accuracy of navigation. The rapid and precise registration by surface matching on the facial skin is possible using the landmarks of the face in the supine position. On the other hand, incomplete registration often occurs in the lateral or prone position due to the direction of the face and displacement of the skin by headpins and obscuring of the skin by the bispectral index monitor and many electrodes on the forehead as well as the eye patch. Surface matching on the occipital scalp is not suitable for registration because the shape of the occipital scalp is flat and it is compressed in the supine position when obtaining preoperative neuroimaging. To overcome this problem, the authors have developed a new method of registration designated as "bony surface registration" in which surface matching is achieved using the bony surface of the skull after exposure. METHODS: Between June and December 2014, this technique was used in 23 patients and its effectiveness was examined. RESULTS: Registration time was markedly shortened and useful navigation was achieved due to accurate registration in all patients. CONCLUSIONS: This is the first report of a registration methodology for a navigation system in the lateral or prone position. This bony surface registration method is useful for navigation system image-guided surgery in the lateral or prone position. PMID- 26276470 TI - Microsurgical resection of an intramedullary glomus arteriovenous malformation in the high cervical spinal cord: retrograde dissection techniques of the nidus located between spinal tracts. AB - BACKGROUND: Spinal intramedullary arteriovenous malformations (AVMs) fed by an anterior spinal artery are surgically challenging vascular lesions. METHOD: We herein presented microsurgical resection techniques for an intramedullary glomus AVM located in the lateral part of the high cervical spinal cord with an operative video. These techniques included (1) a lateral suboccipital approach via cervical hemilaminectomy in the lateral position; (2) retrograde dissection of the AVM located between the spinal tracts; (3) coagulation and division of multiple narrow sulcal branches of the anterior spinal artery. CONCLUSION: Patients who underwent these techniques achieved good outcomes with minimal bleeding and morbidity. PMID- 26276471 TI - Expression of bioactive recombinant human fibroblast growth factor 9 in oil bodies of Arabidopsis thaliana. AB - Fibroblast growth factor 9 (FGF9) has autocrine and paracrine functions in chondrogenesis osteogenesis, hair growth, and gonadal differentiation. We have expressed recombinant human FGF9 (rhFGF9) in the oil bodies of Arabidopsis thaliana via the floral dip method. The expression vector pOTB-rhFGF9 contained an oleosin-rhFGF9 fusion gene and a glufosinate resistance gene for selection. This plasmid was transformed into A. thaliana and expression of the fusion protein oleosin-rhFGF9 confirmed by SDS-PAGE and Western blotting. Furthermore, MTT assays demonstrated that the oil bodies expressed oleosin-rhFGF9 from the transgenic A. thaliana had a remarkable proliferation effect on NIH/3T3 cells. PMID- 26276472 TI - Expression and purification of active recombinant human bone morphogenetic 7-2 dimer fusion protein. AB - Bone morphogenetic proteins (BMPs) have been applied in bone regeneration therapy due to their significant osteogenic activity, however, the complicated processing and high cost in producing recombinant BMP have limited their use in the clinic. In this study, we have developed a simple method to prepare recombinant human BMP7-BMP2 fusion protein with a flexible peptide linker (rhBMP7-2). The rhBMP7-2 protein is expressed efficiently in Escherichia coli, and the denatured protein purified by anion exchange chromatography then refolded by dialysis. The yield was about 6.8 mg per gram of wet cell weight. The bioactivity of re-folded rhBMP7 2 was measured by alkaline phosphatase assay and alizarin red staining using both C2C12 and MC3T3-E1 cells, and also using the rat subcutaneous ectopic bone formation model. High level osteogenic activity was found in all the assays tested demonstrating the production of corrected folded and active rhBMP7-2 protein. PMID- 26276473 TI - Cloning and characterization of a novel thermostable esterase from Bacillus gelatini KACC 12197. AB - A novel gene encoding a thermostable esterase (designated as Est-gela) was isolated from the moderate thermophile Bacillus gelatini KACC 12197. The open reading frame of this gene (1170 bp) encodes 389 amino acid residues, and the molecular weight of Est-gela is approximately 42 kDa. The protein sequence of Est gela shows similarity with beta-lactamases and esterases (? 43%). Est-gela contains the Ser-X-X-Lys conserved sequence (Ser58-Met59-Thr60-Lys61) and belongs to family VIII of esterases. We overexpressed Est-gela in Escherichia coli XL1 blue and purified this protein using a His tag. Est-gela showed a strong enzymatic activity toward p-nitrophenyl esters with short acyl chains (? C4) and the strongest activity toward p-nitrophenyl butyrate. Est-gela showed an enhanced enzymatic activity at 65-75 degrees C and retained more than 90% of the activity after incubation at 65 degrees C for 180 min. These results indicated that Est gela was thermostable. In addition, Est-gela showed the maximal activity at pH 10. We also evaluated the effects of surfactants and organic solvents. Surfactants were more effective at improving the enzymatic activity than were organic solvents. Finally, Est-gela hydrolyzed (R,S)-ketoprofen ethyl ester (Kcat/Km = 5.0 +/- 0.2 s(-1) mM(-1), mean +/- standard error) with enantioselectivity toward (S)-ketoprofen ethyl ester rather than (R)-ketoprofen ethyl ester. PMID- 26276474 TI - Assessment of alkaline cholesterol oxidase purified from Rhodococcus sp. PKPD-CL for its halo tolerance, detergent and organic solvent stability. AB - The novel bacterium, Rhodococcus sp. PKPD-CL was isolated and identified from the 'Chilika Lake' located at Odisha state of India, which is a largest brackish water habitat in Asia. Rhodococcus sp. PKPD-CL produces extracellular halo tolerant, detergent and organic solvent stable alkaline cholesterol oxidase. It has apparent molecular weight of 60 kDa and was purified 59 fold by using 60% saturated ammonium sulfate fractionation, anion exchange followed by size exclusion chromatographic techniques with 37% recovery. It showed substrate specificity for 3beta-hydroxysteroids with Km of 1.1 * 10(-4)M for cholesterol. The pH, 8.0 and the temperature, 37 degrees C were required for its optimum activity. Enzyme is considerably stable at pH 6.0-8.5 and temperature up to 50 degrees C. At 4 and 30 degrees C it maintained its 100% activity up to 60 days. The isoelectric point of the enzyme was 9.5. It showed 80% residual activity with 20% NaCl (3.42 M) and 83% relative activity with 12% NaCl (2.05 M) concentration. The metal ions like Zn(2+), Cu(2+), Ag+, Fe(3+), Ba(2+) inhibited the enzyme activity >60% while Hg(2+) served a potent inhibitor whereas Mg(2+) found to be a good enhancer for it. The enzyme was stable in presence of chemical reagents (NaN3, EDTA), detergents (Tween-80, Tween-20, Triton X-100, sodium cholate) and various organic solvents (isopropanol, ethanol, benzene, chloroform, methanol, toluene, ethyl acetate, butanol and dimethylsulfoxide). Such a multi stress tolerant and versatile enzyme produced by Rhodococcus sp. PKPD-CL may serve as a good choice for industrial applications. PMID- 26276475 TI - How Geometric Distortions Scatter Electronic Excitations in Conjugated Macromolecules. AB - Effects of disorder and exciton-phonon interactions are the major factors controlling photoinduced dynamics and energy-transfer processes in conjugated organic semiconductors, thus defining their electronic functionality. All-atom quantum-chemical simulations are potentially capable of describing such phenomena in complex "soft" organic structures, yet they are frequently computationally restrictive. Here we efficiently characterize how electronic excitations in branched conjugated molecules interact with molecular distortions using the exciton scattering (ES) approach as a fundamental principle combined with effective tight-binding models. Molecule geometry deformations are incorporated to the ES view of electronic excitations by identifying the dependence of the Frenkel-type exciton Hamiltonian parameters on the characteristic geometry parameters. We illustrate our methodology using two examples of intermolecular distortions, bond length alternation and single bond rotation, which constitute vibrational degrees of freedom strongly coupled to the electronic system in a variety of conjugated systems. The effect on excited-state electronic structures has been attributed to localized variation of exciton on-site energies and couplings. As a result, modifications of the entire electronic spectra due to geometric distortions can be efficiently and accurately accounted for with negligible numerical cost. The presented approach can be potentially extended to model electronic structures and photoinduced processes in bulk amorphous polymer materials. PMID- 26276476 TI - Some Like It Hot: The Effect of Sterols and Hopanoids on Lipid Ordering at High Temperature. AB - Sterols and hopanoids have been suggested to reinforce membranes and protect against unfavorable environmental conditions. In particular, hopanoids are found in high concentrations in membranes of thermotolerant and thermophilic bacteria. However, the mechanism whereby sterols and hopanoids stabilize membranes at elevated temperatures is poorly understood. Here, the effect of temperature on the ordering of lipids in bilayers containing cholesterol or the hopanoids bacteriohopanetetrol and diplopterol was explored using molecular dynamics simulations. It is shown that cholesterol induces a high level of ordering over a wide range of temperatures. Bacteriohopanetetrol promotes order within the lipid tails but enhances fluid-like properties of the head groups at high temperatures. In contrast, diplopterol partitions in the midplane of the bilayer. This suggests that individual hopanoids fulfill distinct functions in membranes, with the ordering properties of bacteriohopanetetrol being particularly well suited to maintain the integrity of membranes at temperatures preferred by thermotolerant and thermophilic bacteria. PMID- 26276477 TI - Room-Temperature Optical Tunability and Inhomogeneous Broadening in 2D-Layered Organic-Inorganic Perovskite Pseudobinary Alloys. AB - We focus here our attention on a particular family of 2D-layered and 3D hybrid perovskite molecular crystals, the mixed perovskites (C6H5-C2H4-NH3)2PbZ4(1-x)Y4x and (CH3-NH3)PbZ3(1-x)Y3x, where Z and Y are halogen ions such as I, Br, and Cl. Studying experimentally the disorder-induced effects on the optical properties of the 2D mixed layered materials, we demonstrate that they can be considered as pseudobinary alloys, exactly like Ga1-xAlxAs, Cd1-xHgxTe inorganic semiconductors, or previously reported 3D mixed hybrid perovskite compounds. 2D layered and 3D hybrid perovskites afford similar continuous optical tunability at room temperature. Our theoretical analysis allows one to describe the influence of alloying on the excitonic properties of 2D-layered perovskite molecular crystals. This model is further refined by considering different Bohr radii for pure compounds. This study confirms that despite a large binding energy of several 100 meV, the 2D excitons present a Wannier character rather than a Frenkel character. The small inhomogeneous broadening previously reported in 3D hybrid compounds at low temperature is similarly consistent with the Wannier character of free excitons. PMID- 26276478 TI - Calcium Binding to Calmodulin by Molecular Dynamics with Effective Polarization. AB - Calcium represents a key biological signaling ion with the EF-hand loops being its most prevalent binding motif in proteins. We show using molecular dynamics simulations with umbrella sampling that including electronic polarization effects via ionic charge rescaling dramatically improves agreements with experiment in terms of the strength of calcium binding and structures of the calmodulin binding sites. The present study thus opens way to accurate calculations of interactions of calcium and other computationally difficult high-charge-density ions in biological contexts. PMID- 26276479 TI - RIDME Spectroscopy with Gd(III) Centers. AB - The relaxation induced dipolar modulation enhancement (RIDME) technique is applied at W-band microwave frequencies around 94 GHz to a pair of Gd(III) complexes that are connected by a rodlike spacer, and the extraction of the interspin distance distribution is discussed. A dipolar pattern derived from RIDME experimental data is a superposition of Pake-like dipolar patterns corresponding to the fundamental dipolar interaction and higher harmonics thereof. Intriguingly, the relative weights of the stretched patterns do not depend significantly on mixing time. As much larger modulation depths can be achieved than in double electron-electron resonance distance measurements at the same frequency, Gd(III)-Gd(III) RIDME may become attractive for structural characterization of biomacromolecules and biomolecular complexes. PMID- 26276480 TI - Which Is Better at Predicting Quantum-Tunneling Rates: Quantum Transition-State Theory or Free-Energy Instanton Theory? AB - Quantum transition-state theory (QTST) and free-energy instanton theory (FEIT) are two closely related methods for estimating the quantum rate coefficient from the free-energy at the reaction barrier. In calculations on one-dimensional models, FEIT typically gives closer agreement than QTST with the exact quantum results at all temperatures below the crossover to deep tunneling, suggesting that FEIT is a better approximation than QTST in this regime. Here we show that this simple trend does not hold for systems of greater dimensionality. We report tests on several collinear and three-dimensional reactions, in which QTST outperforms FEIT over a range of temperatures below crossover, which can extend down to half the crossover temperature (below which FEIT outperforms QTST). This suggests that QTST-based methods such as ring-polymer molecular dynamics (RPMD) may often give closer agreement with the exact quantum results than FEIT. PMID- 26276481 TI - Mosaic Texture and Double c-Axis Periodicity of beta-NiOOH: Insights from First Principles and Genetic Algorithm Calculations. AB - Fe-doped NiOx has recently emerged as a promising anode material for the oxygen evolution reaction, but the origin of the high activity is still unclear, due largely to the structural uncertainty of the active phase of NiOx. Here, we report a theoretical study of the structure of beta-NiOOH, one of the active components of NiOx. Using a genetic algorithm search of crystal structures combined with dispersion-corrected hybrid density functional theory calculations, we identify two groups of favorable structures: (i) layered structures with alternate Ni(OH)2 and NiO2 layers, consistent with the doubling of the c axis observed in high resolution transmission electron microscopy (TEM) measurements, and (ii) tunnel structures isostructural with MnO2 polymorphs, which can provide a rationale for the mosaic textures observed in TEM. Analysis of the Ni ions oxidation state further indicates a disproportionation of half of the Ni(3+) cations to Ni(2+)/Ni(4+) pairs. Hybrid density functionals are found essential for a correct description of the electronic structure of beta-NiOOH. PMID- 26276482 TI - Activated Li2S as a High-Performance Cathode for Rechargeable Lithium-Sulfur Batteries. AB - Lithium-sulfur (Li-S) batteries with a high theoretical energy density of ~2500 Wh kg(-1) are considered as one promising rechargeable battery chemistry for next generation energy storage. However, lithium-metal anode degradation remains a persistent problem causing safety concerns for Li-S batteries, hindering their practical utility. One possible strategy to circumvent the aforementioned problems is to use alternative, high-capacity, lithium-free anodes (e.g., Si, Sn, carbon) and a Li2S cathode. However, a large potential barrier was identified on the initial charge of insulating bulk Li2S particles, limiting the cell performance. In this work, the bulk Li2S particles were effectively activated with an electrolyte containing P2S5, resulting in a lowered initial charging voltage plateau. This permits the direct use of commercially available bulk Li2S particles as a high-capacity cathode for room-temperature, rechargeable Li-S batteries, significantly lowering the manufacturing cost of Li-S cells. PMID- 26276483 TI - What Makes Hydroxamate a Promising Anchoring Group in Dye-Sensitized Solar Cells? Insights from Theoretical Investigation. AB - We report, from a theoretical point of view, the first comparative study between the highly water-stable hydroxamate and the widely used carboxylate, in addition to the robust phosphate anchors. Theoretical calculations reveal that hydroxamate would be better for photoabsorption. A quantum dynamics description of the interfacial electron transfer (IET), including the underlying nuclear motion effect, is presented. We find that both hydroxamate and carboxylate would have efficient IET character; for phosphate the injection time is significantly longer (several hundred femtoseconds). We also verified that the symmetry of the geometry of the anchoring group plays important roles in the electronic charge delocalization. We conclude that hydroxamate can be a promising anchoring group, as compared to carboxylate and phosphate, due to its better photoabsorption and comparable IET time scale as well as the experimental advantage of water stability. We expect the implications of these findings to be relevant for the design of more efficient anchoring groups for dye-sensitized solar cell (DSSC) application. PMID- 26276484 TI - Building Physical Chemistry with BRICKs. PMID- 26276485 TI - One-Step Deposition of Photovoltaic Layers Using Iodide Terminated PbS Quantum Dots. AB - We present a one-step layer deposition procedure employing ammonium iodide (NH4I) to achieve photovoltaic quality PbS quantum dot (QD) layers. Ammonium iodide is used to replace the long alkyl organic native ligands binding to the QD surface resulting in iodide terminated QDs that are stabilized in polar solvents such as N,N-dimethylformamide without particle aggregation. We extensively characterized the iodide terminated PbS QD via UV-vis absorption, transmission electron microscopy (TEM), thermogravimetric analysis (TGA), FT-IR transmission spectroscopy, and X-ray photoelectron spectroscopy (XPS). Finally, we fabricated PbS QD photovoltaic cells that employ the iodide terminated PbS QDs. The resulting QD-PV devices achieved a best power conversion efficiency of 2.36% under ambient conditions that is limited by the layer thickness. The PV characteristics compare favorably to similar devices that were prepared using the standard layer-by-layer ethandithiol (EDT) treatment that had a similar layer thickness. PMID- 26276486 TI - Distinguishing between High- and Low-Spin States for Divalent Mn in Mn-Based Prussian Blue Analogue by High-Resolution Soft X-ray Emission Spectroscopy. AB - We combine Mn L2,3-edge X-ray absorption, high resolution Mn 2p-3d-2p resonant X ray emission, and configuration-interaction full-multiplet (CIFM) calculation to analyze the electronic structure of Mn-based Prussian blue analogue. We clarified the Mn 3d energy diagram for the Mn(2+) low-spin state separately from that of the Mn(2+) high-spin state by tuning the excitation energy for the X-ray emission measurement. The obtained X-ray emission spectra are generally reproduced by the CIFM calculation for the Mn(2+) low spin state having a stronger ligand-to-metal charge-transfer effect between Mn t2g and CN pi orbitals than the Mn(2+) high spin state. The d-d-excitation peak nearest to the elastic scattering was ascribed to the Mn(2+) LS state by the CIFM calculation, indicating that the Mn(2+) LS state with a hole on the t2g orbital locates near the Fermi level. PMID- 26276487 TI - Graphitic Phase of NaCl. Bulk Properties and Nanoscale Stability. AB - We applied the ab initio approach to evaluate the stability and physical properties of the nanometer-thickness NaCl layered films and found that the rock salt films with a (111) surface become unstable with thickness below 1 nm and spontaneously split to graphitic-like films for reducing the electrostatic energy penalty. The observed sodium chloride graphitic phase displays an uncommon atomic arrangement and exists only as nanometer-thin quasi-two-dimensional films. The graphitic bulk counterpart is unstable and transforms to another hexagonal wurtzite NaCl phase that locates in the negative-pressure region of the phase diagram. It was found that the layers in the graphitic NaCl film are weakly bounded with each other with a binding energy order of 0.1 eV per stoichiometry unit. The electronic band gap of the graphitic NaCl displays an unusual nonmonotonic quantum confinement response. PMID- 26276488 TI - Plasmon-Enhanced Upconversion. AB - Upconversion, the conversion of photons from lower to higher energies, is a process that promises applications ranging from high-efficiency photovoltaic and photocatalytic cells to background-free bioimaging and therapeutic probes. Existing upconverting materials, however, remain too inefficient for viable implementation. In this Perspective, we describe the significant improvements in upconversion efficiency that can be achieved using plasmon resonances. As collective oscillations of free electrons, plasmon resonances can be used to enhance both the incident electromagnetic field intensity and the radiative emission rates. To date, this approach has shown upconversion enhancements up to 450*. We discuss both theoretical underpinnings and experimental demonstrations of plasmon-enhanced upconversion, examining the roles of upconverter quantum yield, plasmonic geometry, and plasmon spectral overlap. We also discuss nonoptical consequences of including metal nanostructures near upconverting emitters. The rapidly expanding field of plasmon-enhanced upconversion provides novel fundamental insight into nanoscale light-matter interactions while improving prospects for technological relevance. PMID- 26276489 TI - Molecular Friction Mechanisms Across Nanofilms of a Bilayer-Forming Ionic Liquid. AB - The prevailing paradigm in boundary lubrication asserts, in essence, that surfaces coated in amphiphiles slide past each other by way of the "slippery" exposed alkyl chains while the polar head group remains anchored at the surface. Here we show, for ionic liquid boundary lubricants, that the molecular mechanism of shearing is more subtle; while a monolayer on each surface gives rise to alkyl plane shearing, a bilayer on each surface shears at the ionic (nonalkyl) interface. The incorporation of water from the environment dramatically alters the shear at ionic interfaces but leaves alkyl plane shearing unaffected. Our experiments involve shearing two identical and atomically smooth surfaces past one another with films of an ionic liquid between, with subnanometer control of the film thickness and ultrasensitive shear stress resolution. With this, we uncover molecular mechanistic details relevant to boundary lubrication in general and the development of ionic liquid lubricants in particular. PMID- 26276490 TI - Correction to "Morphology and Carrier Extraction Study of Organic-Inorganic Metal Halide Perovskite by One- and Two-Photon Fluorescence Microscopy". PMID- 26276491 TI - ReaxFF Reactive Force-Field Modeling of the Triple-Phase Boundary in a Solid Oxide Fuel Cell. AB - In our study, the Ni/YSZ ReaxFF reactive force field was developed by combining the YSZ and Ni/C/H descriptions. ReaxFF reactive molecular dynamics (RMD) were applied to model chemical reactions, diffusion, and other physicochemical processes at the fuel/Ni/YSZ interface. The ReaxFF RMD simulations were performed on the H2/Ni/YSZ and C4H10/Ni/YSZ triple-phase boundary (TPB) systems at 1250 and 2000 K, respectively. The simulations indicate amorphization of the Ni surface, partial decohesion (delamination) at the interface, and coking, which have indeed all been observed experimentally. They also allowed us to derive the mechanism of the butane conversion at the Ni/YSZ interface. Many steps of this mechanism are similar to the pyrolysis of butane. The products obtained in our simulations are the same as those in experiment, which indicates that the developed ReaxFF potential properly describes complex physicochemical processes, such as the oxide ion diffusion, fuel conversion, water formation reaction, coking, and delamination, occurring at the TPB and can be recommended for further computational studies of the fuel/electrode/electrolyte interfaces in a SOFC. PMID- 26276492 TI - Direct Evidence of Imino Acid-Aromatic Interactions in Native Collagen Protein by DNP-Enhanced Solid-State NMR Spectroscopy. AB - Aromatic amino acids (AAAs) have rare presence (~1.4% abundance of Phe) inside of collagen protein, which is the most abundant animal protein playing a functional role in skin, bone, and connective tissues. The role of AAAs is very crucial and has been debated. We present here experimental results depicting interaction of AAAs with imino acids in a native collagen protein sample. The interaction is probed by solid-state NMR (ssNMR) spectroscopy experiments such as (1)H-(13)C heteronuclear correlation (HETCOR) performed on a native collagen sample. The natural abundance (13)C spectrum was obtained by dynamic nuclear polarization (DNP) sensitivity enhancement coupled with ssNMR, providing ~30-fold signal enhancement. Our results also open up new avenues of probing collagen structure/dynamics closest to the native state by ssNMR experiments coupled with DNP. PMID- 26276493 TI - Direct Characterization of Metal-Metal Bonds between Nuclei with Strong Quadrupolar Interactions via NMR Spectroscopy. AB - Metal-metal bonds can be difficult to characterize directly. We demonstrate that J couplings between metal nuclei experiencing strong quadrupolar interactions can be easily measured from well-defined splittings in NMR spectra of powdered samples. Using (69/71)Ga NMR, it is shown that homonuclear J coupling, which is four orders of magnitude smaller than the quadrupolar coupling in a series of compounds featuring gallium-gallium bonds, can be extracted with a 2-D NMR experiment. The dependence of the multiplets on crystal symmetry reveals information on the structures of two Ga-Ga-bonded compounds for which diffraction data are unavailable. Interpretation of the data in a molecular orbital framework provides insight into the nature of the metal-metal bond. PMID- 26276494 TI - Photoexcited Carrier Dynamics of Cu2S Thin Films. AB - Copper sulfide is a simple binary material with promising attributes for low-cost thin film photovoltaics. However, stable Cu2S-based device efficiencies approaching 10% free from cadmium have yet to be realized. In this Letter, transient absorption spectroscopy is used to investigate the dynamics of the photoexcited state of isolated Cu2S thin films prepared by atomic layer deposition or vapor-based cation exchange of ZnS. While a number of variables including film thickness, carrier concentration, surface oxidation, and grain boundary passivation were examined, grain structure alone was found to correlate with longer lifetimes. A map of excited state dynamics is deduced from the spectral evolution from 300 fs to 300 MUs. Revealing the effects of grain morphology on the photophysical properties of Cu2S is a crucial step toward reaching high efficiencies in operationally stable Cu2S thin film photovoltaics. PMID- 26276495 TI - Photochemical Upconversion: The Primacy of Kinetics. AB - Incoherent photochemical upconversion is a process by which low-energy light can be converted into a higher-energy form with promising applications in solar energy conversion and storage, photocatalysis, biological imaging, and photochemical drug activation. Despite intensive research in recent years, there remains an underappreciation of the chemical kinetics that controls the efficiency of the upconversion process. Here, we provide a brief overview of research into photochemical upconversion and provide a tutorial to guide the design of efficient upconversion compositions. We further provide our perspective on where this area of research is heading and how very efficient systems will be developed. PMID- 26276497 TI - Neurovirulence comparison of chikungunya virus isolates of the Asian and East/Central/South African genotypes from Malaysia. AB - Chikungunya virus (CHIKV), an alphavirus of the family Togaviridae, causes fever, polyarthritis and rash. There are three genotypes: West African, Asian and East/Central/South African (ECSA). The latter two genotypes have caused global outbreaks in recent years. Recent ECSA CHIKV outbreaks have been associated with severe neurological disease, but it is not known if different CHIKV genotypes are associated with different neurovirulence. In this study, the neurovirulence of Asian (MY/06/37348) and ECSA (MY/08/065) strains of CHIKV isolated in Malaysia were compared. Intracerebral inoculation of either virus into suckling mice was followed by virus titration, histopathology and gene expression analysis of the harvested brains. Both strains of CHIKV replicated similarly, yet mice infected with MY/06/37348 showed higher mortality. Histopathology findings showed that both CHIKV strains spread within the brain (where CHIKV antigen was localized to astrocytes and neurons) and beyond to skeletal muscle. In MY/06/37348-infected mice, apoptosis, which is associated with neurovirulence in alphaviruses, was observed earlier in brains. Comparison of gene expression showed that a pro apoptotic gene (eIF2alphaK2) was upregulated at higher levels in MY/06/37348 infected mice, while genes involved in anti-apoptosis (BIRC3), antiviral responses and central nervous system protection (including CD40, IL-10RA, MyD88 and PYCARD) were upregulated more highly in MY/08/065-infected mice. In conclusion, the higher mortality observed following MY/06/37348 infection in mice is due not to higher viral replication in the brain, but to differentially expressed genes involved in host immune responses. These findings may help to identify therapeutic strategies and biomarkers for neurological CHIKV infections. PMID- 26276496 TI - Oil biosynthesis in a basal angiosperm: transcriptome analysis of Persea Americana mesocarp. AB - BACKGROUND: The mechanism by which plants synthesize and store high amounts of triacylglycerols (TAG) in tissues other than seeds is not well understood. The comprehension of controls for carbon partitioning and oil accumulation in nonseed tissues is essential to generate oil-rich biomass in perennial bioenergy crops. Persea americana (avocado), a basal angiosperm with unique features that are ancestral to most flowering plants, stores ~ 70 % TAG per dry weight in its mesocarp, a nonseed tissue. Transcriptome analyses of select pathways, from generation of pyruvate and leading up to TAG accumulation, in mesocarp tissues of avocado was conducted and compared with that of oil-rich monocot (oil palm) and dicot (rapeseed and castor) tissues to identify tissue- and species-specific regulation and biosynthesis of TAG in plants. RESULTS: RNA-Seq analyses of select lipid metabolic pathways of avocado mesocarp revealed patterns similar to that of other oil-rich species. However, only some predominant orthologs of the fatty acid biosynthetic pathway genes in this basal angiosperm were similar to those of monocots and dicots. The accumulation of TAG, rich in oleic acid, was associated with higher transcript levels for a putative stearoyl-ACP desaturase and endoplasmic reticulum (ER)-associated acyl-CoA synthetases, during fruit development. Gene expression levels for enzymes involved in terminal steps to TAG biosynthesis in the ER further indicated that both acyl-CoA-dependent and independent mechanisms might play a role in TAG assembly, depending on the developmental stage of the fruit. Furthermore, in addition to the expression of an ortholog of WRINKLED1 (WRI1), a regulator of fatty acid biosynthesis, high transcript levels for WRI2-like and WRI3-like suggest a role for additional transcription factors in nonseed oil accumulation. Plastid pyruvate necessary for fatty acid synthesis is likely driven by the upregulation of genes involved in glycolysis and transport of its intermediates. Together, a comparative transcriptome analyses for storage oil biosynthesis in diverse plants and tissues suggested that several distinct and conserved features in this basal angiosperm species might contribute towards its rich TAG content. CONCLUSIONS: Our work represents a comprehensive transcriptome resource for a basal angiosperm species and provides insight into their lipid metabolism in mesocarp tissues. Furthermore, comparison of the transcriptome of oil-rich mesocarp of avocado, with oil-rich seed and nonseed tissues of monocot and dicot species, revealed lipid gene orthologs that are highly conserved during evolution. The orthologs that are distinctively expressed in oil-rich mesocarp tissues of this basal angiosperm, such as WRI2, ER-associated acyl-CoA synthetases, and lipid-droplet associated proteins were also identified. This study provides a foundation for future investigations to increase oil-content and has implications for metabolic engineering to enhance storage oil content in nonseed tissues of diverse species. PMID- 26276498 TI - Maternal history of childhood sexual abuse and preterm birth: an epidemiologic review. AB - BACKGROUND: History of childhood sexual abuse (CSA) is highly prevalent with as many as one in four American women being victims. Exposure to CSA or other early life traumatic experiences has been associated with adverse reproductive and pregnancy outcomes. However, the effects of CSA on preterm delivery (PTB), a leading cause of neonatal mortality, remain poorly understood. The objectives of this review are (i) to synthesize the available research investigating the relationship between maternal history of childhood sexual abuse (CSA) and preterm delivery (PTB); (ii) to provide suggestions for improving future research on this topic; and (iii) to highlight implications for clinical practice and public health. METHODS: Relevant articles were identified through searches of four electronic databases (PubMed, CINAHL, Web of Science Core Collection and BIOSIS Online) for studies published before March 2014, as well as through reviewing references of published articles. RESULTS: A total of six studies published from 1992 to 2010 were included in this review. Overall, findings were inconsistent. Three studies reported statistically significant associations of CSA with PTB (<37 weeks gestation) or shorter mean gestational age at birth. Women with a history of CSA had 2.6 to 4.8-fold increased odds of PTB as compared with women without a history of CSA. Three other studies did not observe statistically significant differences in rates of PTB or mean gestational age at birth in relation to a history of CSA. CONCLUSIONS: Available evidence on this topic is sparse and inconsistent, and limited by a number of methodological challenges. Given the ubiquity of CSA, as well as the clinical and public health significance of PTB, more rigorously designed epidemiologic studies on the association between CSA and PTB are warranted. PMID- 26276499 TI - Melioidosis in Hainan, China: a restrospective study. AB - BACKGROUND: Melioidosis is a tropical disease caused by infection with Burkholderia pseudomallei. Here, we report an 11 year (2002-2013) retrospective study of melioidosis cases in China. METHODS: A total of 170 culture-confirmed melioidosis cases were included in our analysis, with culture-positive confirmation, biochemical identification and 16S DNA sequencing. A retrospective study design was employed and a correlational analysis of potential risk factors for mortality was carried out with logistic regression. RESULTS: We observed a year-over-year increasing trend in the incidence of melioidosis in Hainan, particularly after 2007 (annual peak of 64 cases in 2012). Farmers and fishers were the main group susceptible to melioidosis (75/170; 44.1%). Forty-six (27.1%) of the cases were fatal. Pneumonia (58/170; 34.1%) and septicaemia (44/170; 25.9%) were common presentations. Meanwhile, pre-existing diabetes (74/170; 43.5%) and being employed in a job that involves outdoor labour (148/170; 87.1%) emerged as common factors among affected patients. We did not observe a significant effect of seasonal variation on melioidosis mortality, but the greatest number of cases did occur in the rainiest season. CONCLUSIONS: This was the first clinical retrospective study of melioidosis in Hainan, China. The present data will be a useful resource to melioidosis researchers worldwide. PMID- 26276500 TI - "We Are in This Together": Common Group Identity Predicts Majority Members' Active Acculturation Efforts to Integrate Immigrants. AB - Although integration involves a process of mutual accommodation, the role of majority groups is often downplayed to passive tolerance, leaving immigrants with the sole responsibility for active integration. However, we show that common group identity can actively involve majority members in this process across five studies. Study 1 showed that common identity positively predicted support of integration efforts; Studies 2 and 3 extended these findings, showing that it also predicted real behavior such as monetary donations and volunteering. A decrease in modern racism mediated the relations across these studies, and Studies 4 and 5 further demonstrated that it indeed mediated these effects over and above acculturation expectations and color-blindness, which somewhat compromised integration efforts. Moreover, the last two studies also demonstrated that common, but not dual, groups motivated integration efforts. Common identity appears crucial for securing majorities' altruistic efforts to integrate immigrants and, thus, for achieving functional multiculturalism. PMID- 26276501 TI - Pharmacokinetic properties and safety profile of histamine dihydrochloride injection in Chinese healthy volunteers: a phase I, single-center, open-label, randomized study. AB - PURPOSE: Histamine dihydrochloride (HDC) injection has been approved in Europe for the treatment of adults with acute myeloid leukemia, used in combination therapy with the T-cell-derived cytokine interleukin-2. Despite years of clinical applications of HDC in Europe, no data are available on its tolerability and pharmacokinetic properties in Chinese patients. The objective of this study was to determine the safety profile and pharmacokinetic properties of HDC in Chinese healthy volunteers (HVs). METHODS: In this Phase I, single-center, open-label, randomized study, 20 Chinese HVs were randomized to receive a single dose of 0.5 or 1.0 mg HDC via a 10-minute subcutaneous injection. Whole-blood and urine samples were collected at designated time points after dosing. Plasma and urine concentrations of histamine and metabolite N-methyl histamine were measured using a validated HPLC-MS/MS method. Pharmacokinetic parameters were estimated through noncompartmental procedures based on concentration-time data. Adverse events and evaluation of clinical laboratory tests were used to assess the safety profile. The pharmacokinetic profile for a single-dose of 1.0 mg HDC in Chinese HVs was compared with that in Western HVs. FINDINGS: No severe adverse events occurred in this study, and the severity of all adverse events was grade I according to the Common Terminology Criteria for Adverse Events, version 4.0. For the pharmacokinetic parameters of histamine at the 0.5-mg and 1.0-mg dose levels, t1/2 was 0.50 and 1.02 hours; Tmax was 0.15 and 0.14 hours; mean Cmax was 26.59 and 71.01 nmol/L; AUC0-t was 8.35 and 20.43 nmol/h/L; AUC0-infinity was 9.61 and 22.69 nmol/h/L; accumulated amount excreted in urine within 24 hours was 125.93 and 145.52 nmol; and maximum urine excretion rates were 21.85 and 38.94 nmol/h, respectively. For N-methyl histamine at the 0.5-mg and 1.0-mg dose levels, t1/2 was 0.58 and 0.66 hours; Tmax was 0.28 and 0.26 hours; mean Cmax was 17.01 and 23.54 nmol/L; AUC0-t was 7.72 and 17.08 nmol/h/L; AUC0-infinity was 9.01 and 19.62 nmol/h/L; accumulated amount excreted in urine within 24 hours was 331.7 and 583.21 nmol; and maximum urine excretion rates were 53.29 and 133.53 nmol/h, respectively. IMPLICATIONS: Both single-dose 0.5 mg and 1.0 mg HDC were well tolerated in Chinese HVs, and the pharmacokinetic profile of HDC in Chinese HVs was characterized in this study. A single dose of 1.0 mg HDC had a more rapid but similar extent of absorption, a wider distribution, and a little more rapid elimination in Chinese HVs compared with Western HVs. Findings from this study support additional clinical trials for HDC using in Chinese patients. Chinese Clinical Trial Registry identifier: ChiCTR-ONC-13003954. PMID- 26276502 TI - Steatosis and hepatitis C. AB - Hepatitis C virus (HCV) infection is a common liver disease worldwide with a high rate of chronicity (75-80%) in infected individuals. The chronic form of HCV leads to steatosis, cirrhosis and hepatocellualr carcinoma. Steatosis is prevalent in HCV patients (55%) due to a combination of viral factors (effect of viral proteins on some of the intracellular pathways) and host factors (overweight, insulin resistance, diabetes mellitus, and alcohol consumption). The response rates to treatment of chronic HCV with pegylated interferon (PEG-IFN) and (in the case of genotype-1 HCV, the most common infecting genotype in the USA) ribavirin (RBV) is low, with a sustained viral response rate <= 40%. Adding direct-acting antiviral agents-recently approved by the FDA-to the standard protocol has increased the response rate; however HCV-related end-stage liver disease is still the primary indication for liver transplantation in the USA. The focus of this article is on the interrelation between HCV, steatosis and metabolic syndrome. PMID- 26276503 TI - Spontaneous magnetic gastrojejunal fistula caused by accidentally ingested lithium batteries. PMID- 26276505 TI - The pain of being misunderstood: Invalidation of pain complaints in chronic low back pain patients. AB - A particular form of social pain is invalidation. Therefore, this study (a) investigates whether patients with chronic low back pain experience invalidation, (b) if it has an influence on their pain, and (c) explores whether various social sources (e.g. partner and work) influence physical pain differentially. A total of 92 patients completed questionnaires, and for analysis, Pearson's correlation coefficients and hierarchical linear regression analyses were conducted. They indicated a significant association between discounting and disability due to pain (respective beta = .29, p > .05). Especially, discounting by partner was linked to higher disability ( beta = .28, p > .05). PMID- 26276504 TI - TGF-beta1-induced miR-202 mediates drug resistance by inhibiting apoptosis in human osteosarcoma. AB - PURPOSE: A number of studies have demonstrated that microRNAs play a critical role in osteosarcoma progression, therapy and drug resistance. MicroRNA-202 has proven to be dysregulated in many human cancer studies. This study aimed to explore miR-202 contributions to drug resistance in osteosarcoma. METHODS: miR 202 expression was measured by real-time PCR in patient tissues, cell lines or cells treated with TGF-beta1, using siRNA to knock down the expression of Smad2, Smad3 and Smad4. miR-202 mimics, inhibitor and scramble siRNA were transfected into osteosarcoma cells to observe effects on cell apoptosis and drug resistance. Moreover, relationships of miR-202 level with PDCD4 were investigated by luciferase reporter assay, real-time PCR and Western blotting. RESULTS: We found that miR-202 is overexpressed in osteosarcoma tissues when compared with normal human osteoblasts and TGF-beta1 can induce the expression of miR-202. Transfection of miR-202 mimics into osteosarcoma cell lines significantly promotes chemotherapy resistance by targeting PDCD4, a tumor suppressor which is involved in apoptosis. In contrast, transfection of miR-202 inhibitor enhances the drug sensitivity and apoptosis. CONCLUSIONS: This study provides new insights into miRNA-202 in osteosarcoma as a potential molecular target for chemotherapy. PMID- 26276506 TI - Integrative network-based analysis of mRNA and microRNA expression in 1,25 dihydroxyvitamin D3-treated cancer cells. AB - Nutritional systems biology is an evolving research field aimed at understanding nutritional processes at a systems level. It is known that the development of cancer can be influenced by the nutritional status, and the link between vitamin D status and different cancer types is widely investigated. In this study, we performed an integrative network-based analysis using a publicly available data set studying the role of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in prostate cancer cells on mRNA and microRNA level. Pathway analysis revealed 15 significantly altered pathways: eight more general mostly cell cycle-related pathways and seven cancer-specific pathways. The changes in the G1-to-S cell cycle pathway showed that 1,25(OH)2D3 down-regulates the genes influencing the G1 to-S phase transition. Moreover, after 1,25(OH)2D3 treatment the gene expression in several cancer-related processes was down-regulated. The more general pathways were merged into one network and then extended with known protein-protein and transcription factor-gene interactions. Network algorithms were used to (1) identify active network modules and (2) integrate microRNA regulation in the network. Adding microRNA regulation to the network enabled the identification of gene targets of significantly expressed microRNAs after 1,25(OH)2D3 treatment. Six of the nine differentially expressed microRNAs target genes in the extended network, including CLSPN, an important checkpoint regulator in the cell cycle that was down-regulated, and FZD5, a receptor for Wnt proteins that was up regulated. The extendable network-based tools PathVisio and Cytoscape enable straightforward, in-depth and integrative analysis of mRNA and microRNA expression data in 1,25(OH)2D3-treated cancer cells. PMID- 26276507 TI - Antifibrogenic role of valproic acid in streptozotocin induced diabetic rat penis. AB - We investigated the therapeutic effects of valproic acid (VPA) on erectile dysfunction and reducing penile fibrosis in streptozocin (STZ)-induced diabetic rats. Eighteen male rats were divided into three experimental groups (Control, STZ-DM, STZ-DM plus VPA) and diabetes was induced by transperitoneal single dose STZ. Eight weeks after, VPA and placebo treatments were given according to groups for 15 days. All rats were anesthetised for the measurement of in vivo erectile response to cavernous nerve stimulation. Afterward penes were evaluated histologically in terms of immune labelling scores of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and transforming growth factor-beta1 (TGF-beta1). Slides were also evaluated in terms of collagen/smooth muscle ratio and penile apoptosis. After the treatment with VPA, erectile responses were found as improved when compared with STZ-DM rats but not statistically meaningful. eNOS and VEGF immune expressions diminished in penile corpora of STZ-DM rats and improved with VPA treatment. VPA led to decrease in TGF-beta1 expression and collagen content of diabetic rats' penes. Penile apoptosis was not diminished with VPA. In conclusion, VPA treatment seems to be effective for reducing penile fibrosis in diabetic rats and more prolonged treatment period may enhance erectile functions. PMID- 26276508 TI - Transthoracic two-dimensional xPlane and three-dimensional echocardiographic analysis of the site of mitral valve prolapse. AB - This study sought to assess the value of two-dimensional (2D) transthoracic echocardiography (TTE), 2D xPlane imaging and three-dimensional (3D) TTE for the definition of the site and the extent of mitral valve (MV) prolapse. Fifty patients underwent transthoracic 2D, 2D xPlane and 3D echocardiography. With 2D xPlane a segmental analysis of the MV was performed, by making a lateral sweep across the MV coaptation line as seen in the parasternal short-axis view. Inter observer agreement for specific scallop prolapse was for 2D xPlane excellent (97%, kappa = 0.94) and for 3D TTE moderate (85%, kappa = 0.67). The respective sensitivities of standard 2D TTE, 2D xPlane, and 3D TTE for the identification of the precise posterior scallop prolapse were for P1 92, 85, and 92%, for P2 96, 96, and 82%, and for P3 86, 81, and 71%. In total, 5 (8%) prolapsing MV scallops were missed by 2D TTE, 7 (12%) by 2D xPlane, and 12 (20%) by 3D TTE. The sensitivity of 3D TTE was significantly lower than standard 2D imaging (80% versus 93%, P < 0.05). The extent of P2 prolapse was under or overestimated in 5 patients with 2D xPlane and in 9 patients with 3D TTE. 2D xPlane imaging is an accurate, easy to use (compared to 3D TTE) and easy to interpret (compared to 2D and 3D TTE) imaging modality to study the site and the extent of MV prolapse. PMID- 26276509 TI - Cytotoxic T cell vaccination with PLGA microspheres interferes with influenza A virus replication in the lung and suppresses the infectious disease. AB - Current influenza virus vaccines aim to elicit antibodies directed toward viral surface glycoproteins, which however are prone to antigenic drift. Cytotoxic T lymphocytes (CTLs) can exhibit heterosubtypic immunity against most influenza A viruses. In our study, we encapsulated the highly conserved, immunodominant, HLA A*0201 restricted epitope from the influenza virus matrix protein M158-66 together with TLR ligands in biodegradable poly(d,l-lactide-co-glycolide) (PLGA) microspheres. Subcutaneous immunization of transgenic mice expressing chimeric HLA-A*0201 molecules with these microspheres induced a strong and sustained CTL response which sufficed to prevent replication of a recombinant vaccinia virus expressing the influenza A virus (IAV) matrix protein but not the replication of IAV in the lung. However, subcutaneous priming followed by intranasal boosting with M158-66 bearing PLGA microspheres was able to induce vigorous CTL responses both in the lung and spleen of mice which interfered with IAV replication, weight loss, and infection-related death. Taken together, vaccination with well-defined and highly conserved IAV-derived CTL epitopes encapsulated into clinically compatible PLGA microspheres contribute to the control of influenza A virus infections. The promptitude and broad reactivity of the CTL response may help to attenuate pandemic outbreaks of influenza viruses. PMID- 26276510 TI - Superagonism at G protein-coupled receptors and beyond. AB - Ligands targeting GPCRs can be categorized according to their intrinsic efficacy to trigger a specific, receptor-mediated response. A ligand endowed with the same level of efficacy as the endogenous agonist can be classified as a full agonist, whereas a compound that displays greater efficacy, that is, higher receptor signalling output than the endogenous agonist, can be called a superagonist. Subsequent to GPCR activation, an intracellular signalling cascade is set in motion, which may generate substantial amplification of the signal. This may obscure superagonism in pharmacological assays and, therefore, the definition of superagonism necessitates a combination of operational approaches, reduction of spare receptors or estimation of receptor activation close to the receptor level to quantify relative agonist efficacies in a particular system. The first part of this review will compare GPCR superagonism with superagonism in the field of immunology, where this term is well established. In the second part, known GPCR superagonists will be reviewed. Then, the experimental and analytical challenges in the deconvolution of GPCR superagonism will be addressed. Finally, the potential benefit of superagonism is discussed. The molecular mechanisms behind GPCR superagonism are not completely understood. However, crystallography shows that agonist binding alone is not sufficient for a fully active receptor state and that binding of the G protein is at least equally important. Accordingly, the emerging number of reported superagonists implies that ligand-induced receptor conformations more active than the ones stabilized by the endogenous agonist are indeed feasible. Superagonists may have therapeutic potential when receptor function is impaired or to induce negative feedback mechanisms. Linked Articles This article is part of a themed section on Molecular Pharmacology of G Protein Coupled Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.20/issuetoc. PMID- 26276511 TI - Effects of Exercise on Select Biomarkers and Associated Outcomes in Chronic Pain Conditions: Systematic Review. AB - BACKGROUND: Chronic pain is highly prevalent. Current management is challenged by lack of validated objective measures like biological markers. Clinical pain studies employing exercise interventions have evaluated biomarkers; however, it is unclear how exercise impacts biomarkers involved in pain pathways and whether these markers are associated with relevant pain-related outcomes. This systematic review evaluates data from clinical studies employing exercise interventions in chronic musculoskeletal nonmalignant pain conditions in which biomarkers in pain pathways were measured. METHOD: Published research studies from several databases were examined using the Jadad Scale for assessing the quality of clinical studies. RESULTS: Twelve research studies were reviewed. Jadad scores ranged from 5 to 11 out of 13 points. Inflammatory markers were most commonly measured followed by neurotransmitter-related genes and metabolite-detecting genes. After exercise interventions, changes in biomarkers involved in neurotransmission and inflammation suggest a hypoalgesic exercise effect. Significant biomarker associations were found with pain intensity, fatigue, depression, anxiety, and quality of life. However, there were varying methodologies in the studies reviewed. DISCUSSION: It remains a question whether biomarkers can be used as objective measures for risk assessment, diagnosis, or evaluation or as surrogate endpoints in chronic pain. Adequate sample sizes, optimal exercise dose determination, study replications, and longitudinal research studies with consistent methodologies are warranted. Regardless, the potential translational value of biomarkers in chronic pain is evident. Advancing nursing research in biomarkers is vital for moving the nursing discipline and clinical chronic pain practice forward. Developing a biobehavioral perspective in chronic pain is also necessary for comprehensive management. PMID- 26276512 TI - Tissue Factor and Tissue Factor Pathway Inhibitor in the Wound-Healing Process After Neurosurgery. AB - OBJECTIVES: The aim of the study was to assess the concentrations of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in the blood of patients with a postoperative wound after neurosurgery. METHOD: Participants included 20 adult patients who underwent neurosurgery because of degenerative spine changes. The concentration of TF and TFPI in the patients' blood serum was measured 3 times: before surgery, during the first 24 hr after surgery, and between the 5th and 7th days after surgery. The control group comprised 20 healthy volunteers similar to the patient group with respect to gender and age. RESULTS: A statistically significant difference was observed between TF concentration at all three measurement time points in the research group and TF concentration in the control group (p = .018, p = .010, p = .001). A statistically significant difference was found between TFPI concentration at the second time point in the research group and TFPI concentration in the control group (p = .041). No statistically significant within-subject difference was found between TF concentrations before and after surgery. A statistically significant within subject difference was found between TFPI concentrations within 24 hr after surgery and 5-7 days after surgery (p = .004). CONCLUSION: High perioperative concentrations of TF indicate not only the presence of thrombophilia but also the importance of TF in the wound-healing process. Perioperative changes in TFPI concentrations are related to its compensatory influence on hemostasis in thrombophilic conditions. PMID- 26276513 TI - Convergent validation of EQ-5D-5L in patients with Parkinson's disease. AB - INTRODUCTION: The European Quality of Life Questionnaire 5 level version (EQ-5D 5L) is a recently updated instrument to assess Health-Related Quality of Life (HRQoL) that has not been validated extensively. The main objective of this study was to evaluate the internal consistency and convergent validation of the EQ-5D 5L in a large sample of subjects with Parkinson's disease (PD). METHODS: A cross sectional study was carried out. Consecutive Mexican subjects with PD were included. HRQoL was assessed using the EQ-5D-5L and the PDQ-8. Validity of the EQ 5D-5L was assessed determining its association with clinical ratings of disease severity, as well as correlation with PDQ-8. Additionally, performance was evaluated along predefined groups based on clinical and demographic data of known determinants of quality of life. RESULTS: A total of 585 patients were included for this study. A strong correlation was found between EQ-5D-5L index and PDQ-8 index (Spearman's correlation coefficient=-0.75; p<0.001). Correlation between EQ 5D-5L index and PDQ-8 index remained strong (-0.60 to -0.78; p values <0.001) through all predefined groups. EQ-5D-5L scored higher in those patients with dyskinesia, wearing off, freezing, postural instability, cognitive impairment or depressive mood (p values <0.001). CONCLUSION: The EQ-5D-5L is a valid instrument for evaluating HRQoL in PD, performing adequately irrespective of heterogeneous clinical and demographic characteristics, and showing to be sensitive to features of advanced disease and treatment complications. PMID- 26276514 TI - Convection-enhanced delivery of MANF--volume of distribution analysis in porcine putamen and substantia nigra. AB - Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a 20kDa human protein which has both neuroprotective and neurorestorative activity on dopaminergic neurons and therefore may have application for the treatment of Parkinson's Disease. The aims of this study were to determine the translational potential of convection-enhanced delivery (CED) of MANF for the treatment of PD by studying its distribution in porcine putamen and substantia nigra and to correlate histological distribution with co-infused gadolinium-DTPA using real time magnetic resonance imaging. We describe the distribution of MANF in porcine putamen and substantia nigra using an implantable CED catheter system using co infused gadolinium-DTPA to allow real-time MRI tracking of infusate distribution. The distribution of gadolinium-DTPA on MRI correlated well with immunohistochemical analysis of MANF distribution. Volumetric analysis of MANF IHC staining indicated a volume of infusion (Vi) to volume of distribution (Vd) ratio of 3 in putamen and 2 in substantia nigra. This study confirms the translational potential of CED of MANF as a novel treatment strategy in PD and also supports the co-infusion of gadolinium as a proxy measure of MANF distribution in future clinical studies. Further study is required to determine the optimum infusion regime, flow rate and frequency of infusions in human trials. PMID- 26276515 TI - Critical illness polyneuropathy and myopathy in a rural area in Vietnam. AB - INTRODUCTION: Critical illness polyneuropathy, myopathy and polyneuromyopathy, grouped under the term CIP/CIM, share several risk factors and are associated with debilitating outcomes. OBJECTIVE: To assess the incidence and distribution of CIP/CIM subtypes and evaluate the risk factors and outcomes of CIP/CIM in a rural hospital in Vietnam. METHOD: One hundred and thirty three critically ill patients treated more than ten days in the ICU were enrolled. The Medical Research Council (MRC) sum scores and the Overall Neuropathy Limitations Scale (ONLS) score were calculated and risk factors were monitored. Extensive electrodiagnostic investigations were performed to confirm the diagnosis of CIP/CIM. RESULTS: CIP/CIM was diagnosed in 73 (55%) patients. The distribution of polyneuropathy, myopathy and polyneuromyopathy was 35 (48%), 16 (22%) and 22 (30%), respectively. Independent risk factors included systemic inflammatory response syndrome, shock, and electrolyte disturbances. Compared to patients without CIP/CIM, patients with CIP/CIM experienced a mortality rate of 49% vs. 30%, a length of stay in ICU of 20.3days vs. 14.3days, an ONLS score at day thirty of 4.2 vs. 1.3 and at day ninety of 2.7 vs. 1.8. CONCLUSION: The study revealed that the diagnosis of CIP/CIM was associated with significantly poorer outcomes in comparison to controls. PMID- 26276516 TI - ScreenMasker: An Open-source Gaze-contingent Screen Masking Environment. AB - The moving-window paradigm, based on gazecontingent technic, traditionally used in a studies of the visual perceptual span. There is a strong demand for new environments that could be employed by non-technical researchers. We have developed an easy-to-use tool with a graphical user interface (GUI) allowing both execution and control of visual gaze-contingency studies. This work describes ScreenMasker, an environment that allows create gaze-contingent textured displays used together with stimuli presentation software. ScreenMasker has an architecture that meets the requirements of low-latency real-time eye-movement experiments. It also provides a variety of settings and functions. Effective rendering times and performance are ensured by means of GPU processing under CUDA technology. Performance tests show ScreenMasker's latency to be 67-74 ms on a typical office computer, and high-end 144-Hz screen latencies of about 25-28 ms. ScreenMasker is an open-source system distributed under the GNU Lesser General Public License and is available at https://github.com/PaulOrlov/ScreenMasker . PMID- 26276517 TI - Ratings of age of acquisition of 299 words across 25 languages: Is there a cross linguistic order of words? AB - We present a new set of subjective age-of-acquisition (AoA) ratings for 299 words (158 nouns, 141 verbs) in 25 languages from five language families (Afro-Asiatic: Semitic languages; Altaic: one Turkic language: Indo-European: Baltic, Celtic, Germanic, Hellenic, Slavic, and Romance languages; Niger-Congo: one Bantu language; Uralic: Finnic and Ugric languages). Adult native speakers reported the age at which they had learned each word. We present a comparison of the AoA ratings across all languages by contrasting them in pairs. This comparison shows a consistency in the orders of ratings across the 25 languages. The data were then analyzed (1) to ascertain how the demographic characteristics of the participants influenced AoA estimations and (2) to assess differences caused by the exact form of the target question (when did you learn vs. when do children learn this word); (3) to compare the ratings obtained in our study to those of previous studies; and (4) to assess the validity of our study by comparison with quasi-objective AoA norms derived from the MacArthur-Bates Communicative Development Inventories (MB-CDI). All 299 words were judged as being acquired early (mostly before the age of 6 years). AoA ratings were associated with the raters' social or language status, but not with the raters' age or education. Parents reported words as being learned earlier, and bilinguals reported learning them later. Estimations of the age at which children learn the words revealed significantly lower ratings of AoA. Finally, comparisons with previous AoA and MB CDI norms support the validity of the present estimations. Our AoA ratings are available for research or other purposes. PMID- 26276518 TI - Measuring nonvisual knowledge about object categories: The Semantic Vanderbilt Expertise Test. AB - How much do people differ in their abilities to recognize objects, and what is the source of these differences? To address the first question, psychologists have created visual learning tests including the Cambridge Face Memory Test (Duchaine & Nakayama, 2006) and the Vanderbilt Expertise Test (VET; McGugin et al., 2012). The second question requires consideration of the influences of both innate potential and experience, but experience is difficult to measure. One solution is to measure the products of experience beyond perceptual knowledge specifically, nonvisual semantic knowledge. For instance, the relation between semantic and perceptual knowledge can help clarify the nature of object recognition deficits in brain-damaged patients (Barton, Hanif, & Ashraf, Brain, 132, 3456-3466, 2009). We present a reliable measure of nonperceptual knowledge in a format applicable across categories. The Semantic Vanderbilt Expertise Test (SVET) measures knowledge of relevant category-specific nomenclature. We present SVETs for eight categories: cars, planes, Transformers, dinosaurs, shoes, birds, leaves, and mushrooms. The SVET demonstrated good reliability and domain-specific validity. We found partial support for the idea that the only source of domain specific shared variance between the VET and SVET is experience with a category. We also demonstrated the utility of the SVET-Bird in experts. The SVET can facilitate the study of individual differences in visual recognition. PMID- 26276519 TI - Relative meaning frequencies for 578 homonyms in two Spanish dialects: A cross linguistic extension of the English eDom norms. AB - Relative meaning frequency is a critical factor to consider in studies of semantic ambiguity. In this work, we examined how this measure may change across the European and Rioplatense dialects of Spanish, as well as how the overall distributional properties differ between Spanish and English, using a computer assisted norming approach based on dictionary definitions (Armstrong, Tokowicz, & Plaut, 2012). The results showed that the two dialects differ considerably in terms of the relative meaning frequencies of their constituent homonyms, and that the overall distributions of relative frequencies vary considerably across languages, as well. These results highlight the need for localized norms to design powerful studies of semantic ambiguity and suggest that dialectal differences may be responsible for some discrepant effects related to homonymy. In quantifying the reliability of the norms, we also established that as few as seven ratings are needed to converge on a highly stable set of ratings. This approach is therefore a very practical means of acquiring essential data in studies of semantic ambiguity, relative to past approaches, such as those based on the classification of free associates. The norms also present new possibilities for studying semantic ambiguity effects within and between populations who speak one or more languages. The norms and associated software are available for download at http://edom.cnbc.cmu.edu/ or http://www.bcbl.eu/databases/edom/ . PMID- 26276520 TI - Lisbon Symbol Database (LSD): Subjective norms for 600 symbols. AB - This article presents subjective rating norms for a new set of 600 symbols, depicting various contents (e.g., transportation, technology, and leisure activities) that can be used by researchers in different fields. Symbols were evaluated for aesthetic appeal, familiarity, visual complexity, concreteness, valence, arousal, and meaningfulness. The normative data were obtained from 388 participants, and no gender differences were found. Descriptive results (means, standard deviations, and confidence intervals) for each symbol in each dimension are presented. Overall, the dimensions were highly correlated. Additionally, participants were asked to briefly describe the meaning of each symbol. The results indicate that the present symbol set is varied, allowing for the selection of exemplars with different levels on the seven examined dimensions. This set of symbols constitutes a tool with potential for research in different areas. The database with all of the symbols is available as supplemental materials. PMID- 26276521 TI - Estimating informal care inputs associated with EQ-5D for use in economic evaluation. AB - OBJECTIVES: This paper estimates informal care need using the health of the patient. The results can be used to predict changes in informal care associated with changes in the health of the patient measured using EQ-5D. METHODS: Data was used from a prospective survey of inpatients containing 59,512 complete responses across 44,494 individuals. The number of days a friend or relative has needed to provide care or help with normal activities in the last 6 weeks was estimated using the health of the patient measured by EQ-5D, ICD chapter and other health and sociodemographic data. A variety of different regression models were estimated that are appropriate for the distribution of the informal care dependent variable, which has large spikes at 0 (zero informal care) and 42 days (informal care every day). RESULTS: The preferred model that most accurately predicts the distribution of the data is the zero-inflated negative binomial with variable inflation. The results indicate that improving the health of the patient reduces informal care need. The relationship between ICD chapter and informal care need is not as clear. CONCLUSIONS: The preferred zero-inflated negative binomial with variable inflation model can be used to predict changes in informal care associated with changes in the health of the patient measured using EQ-5D and these results can be applied to existing datasets to inform economic evaluation. Limitations include recall bias and response bias of the informal care data, and restrictions of the dataset to exclude some patient groups. PMID- 26276522 TI - Interleukin 2 Topical Cream for Treatment of Diabetic Foot Ulcer: Experiment Protocol. AB - BACKGROUND: It is estimated there are 2.9 million diabetic patients in the United Kingdom, and around 5%-7% of patients have diabetic ulcers. This number will continue to increase globally. Diabetic ulcers are a major economic burden on the healthcare system. More than L650 million is spent on foot ulcers or amputations each year, and up to 100 people a week have a limb amputated due to diabetes. In T1DM, the level of IL-2 is reduced, and hence, wound healing is in a prolonged inflammatory phase. It is not known if IL-2 topical cream can shorten the healing process in T1DM patients. OBJECTIVE: The objective of this study is to understand the pathophysiology in type 1 diabetes (T1DM) and investigate possible future treatment based on its clinical features. The hypothesis is that IL-2 cream can speed up wound healing in NOD mice and that this can be demonstrated in a ten week study. An experiment protocol is designed in a mouse model for others to conduct the experiment. The discussion is purely based on diabetic conditions; lifestyle influences like smoking and drinking are not considered. METHODS: Skin incisions will be created on 20 nonobese diabetic (NOD) mice, and IL-2 topical cream will be applied in a 10-week study to prove the hypothesis. Mice will be randomly and equally divide into two groups with one being the control group. RESULTS: T1DM patients have a decreased number of T regulatory (Treg) cells and interleukin 2 (IL-2). These are the keys to the disease progression and delay in wound healing. Diabetic ulcer is a chronic wound and characterized by a prolonged inflammatory phase. CONCLUSIONS: If the experiment is successful, T1DM patients will have an alternative, noninvasive treatment of foot ulcers. In theory, patients with other autoimmune diseases could also use IL-2 topical cream for treatment. PMID- 26276523 TI - Association between variants in inflammation and cancer-associated genes and risk and survival of cholangiocarcinoma. AB - Genetic risk factors for cholangiocarcinoma (CCA) remain poorly understood. We assessed the effect of single-nucleotide polymorphisms (SNPs) of genes modulating inflammation or carcinogenesis on CCA risk and survival. We conducted a case control, candidate gene association study of 370 CCA patients and 740 age-, sex-, and residential area-matched healthy controls. Eighteen functional or putatively functional SNPs in nine genes were genotyped. The log-additive genotype effects of SNPs on CCA risk and survival were determined using logistic regression and the log-rank test, respectively. Initial analysis identified significant associations between SNP rs2143417 and rs689466 in cyclooxygenase 2 (COX-2) and CCA risk, after adjusting for multiple comparisons (cutoff of P = 0.0028). However, these findings were not replicated in another independent cohort of 212 CCA cases and 424 matched controls. No significant association was found between any SNP and survival of CCA patients. Although COX-2 has been shown to contribute to cholangiocarcinogenesis, the COX-2 SNPs tested were not associated with risk of CCA. This study shows a lack of association between variants of genes related to inflammation and carcinogenesis and CCA risk and survival. Other factors than these genetic variants may play more important roles in CCA risk and survival. PMID- 26276524 TI - Diversity, specificity and speciation in larval Diplostomidae (Platyhelminthes: Digenea) in the eyes of freshwater fish, as revealed by DNA barcodes. AB - Larvae (metacercariae) in some species of Diplostomidae (Platyhelminthes: Digenea) inhabit fish eyes and are difficult to identify to species based on morphology. DNA barcoding has clarified the diversity and life cycles of diplostomids in North America, Europe and Africa, but has seldom been used in parasites sampled in large numbers or at large spatial scales. Here, distance based analysis of cytochrome c oxidase 1 barcodes and, in some specimens, internal transcribed spacer (ITS-1, 5.8S, ITS-2) sequences was performed for over 2000 diplostomids from Africa, the Middle East, Europe, Asia and the Americas. Fifty-two species of Diplostomum, Tylodelphys and Austrodiplostomum (Digenea: Diplostomidae) were distinguished. The 52 species comprise 12 identified species, six species in two species complexes and 34 putative species, and 33/52 had been delineated in previous studies. Most (23/40) of the unidentified, putative species distinguished by cytochrome c oxidase 1 distances were supported by at least one additional line of evidence. As the intensity of sampling of the 52 species increased, variation in cytochrome c oxidase 1 decreased between and increased within species, while the spatial scale at which species were sampled had no effect. Nonetheless, variation between species always exceeded variation within species. New life-cycle linkages, geographic and host records, and genetic data were recorded in several species, including Tylodelphys jenynsiae, Tylodelphys immer and Diplostomum ardeae. Species of Diplostomum inhabiting the lens are less host-specific and less numerous than those infecting other tissues, suggesting that reduced immune activity in the lens has influenced rates of speciation. PMID- 26276525 TI - Autologous vein graft stenosis inhibited by orphan nuclear receptor Nur77 targeted siRNA. AB - Neointimal hyperplasia plays an important role in autologous vein graft stenosis, and orphan receptor TR3/nur77 (Nur77) might play an essential role, but the mechanisms are still unclear. Here, we investigated the function of Nur77 in autologous vein graft stenosis. Rat vascular smooth muscle cell A7r5 was used for evaluating the function of Nur77 and screen siRNAs. Meanwhile, rat vein graft models were constructed for investigating the stenosis inhibition effects of Nur77-targeted siRNAs. The mRNA and protein levels of Nur77 were highly expressed in A7r5 cell, and could be significantly inhibited by the pre-designed siRNAs; the proliferation of A7r5 cell was also inhibited by the siRNAs. Furthermore, the intimal thickening in rat vein graft models was inhibited when knocking down the expression of Nur77 by siRNA. The results suggest that Nur77-targeted siRNA can inhibit autologous vein graft stenosis, Nur77 may play an important role in autologous vein graft stenosis, and Nur77 targeted siRNAs may be a therapy method for anti-stenosis of autologous vein graft. PMID- 26276526 TI - Endothelial cell tetrahydrobiopterin deficiency attenuates LPS-induced vascular dysfunction and hypotension. AB - Overproduction of nitric oxide (NO) is thought to be a key mediator of the vascular dysfunction and severe hypotension in patients with endotoxaemia and septic shock. The contribution of NO produced directly in the vasculature by endothelial cells to the hypotension seen in these conditions, vs. the broader systemic increase in NO, is unclear. To determine the specific role of endothelium derived NO in lipopolysaccharide (LPS)-induced vascular dysfunction we administered LPS to mice deficient in endothelial cell tetrahydrobiopterin (BH4), the essential co-factor for NO production by NOS enzymes. Mice deficient in endothelial BH4 production, through loss of the essential biosynthesis enzyme Gch1 (Gch1(fl/fl)Tie2cre mice) received a 24hour challenge with LPS or saline control. In vivo LPS treatment increased vascular GTP cyclohydrolase and BH4 levels in aortas, lungs and hearts, but this increase was significantly attenuated in Gch1(fl/fl)Tie2cre mice, which were also partially protected from the LPS-induced hypotension. In isometric tension studies, in vivo LPS treatment reduced the vasoconstriction response and impaired endothelium-dependent and independent vasodilatations in mesenteric arteries from wild-type mice, but not in Gch1(fl/fl)Tie2cre mesenteric arteries. Ex vivo LPS treatment decreased vasoconstriction response to phenylephrine in aortic rings from wild-type and not in Gch1(fl/fl)Tie2cre mice, even in the context of significant eNOS and iNOS upregulation. These data provide direct evidence that endothelial cell NO has a significant contribution to LPS-induced vascular dysfunction and hypotension and may provide a novel therapeutic target for the treatment of systemic inflammation and patients with septic shock. PMID- 26276527 TI - Glioblastoma recurrence patterns near neural stem cell regions. AB - PURPOSE: Glioblastoma (GBM) cancer stem cells and their neural stem cell counterparts are hypothesized to contribute to tumor progression. We examined whether GBM contrast enhancement contact with neurogenic regions (NR) affect recurrence patterns, as contrast enhancement reflects regions of blood-brain barrier breakdown. METHODS: 102 patients with primary GBM, treated at Johns Hopkins Hospital between 2006 and 2009, were included. All patients underwent surgical resection followed by adjuvant IMRT (60 Gy/30 fractions) and concomitant temozolomide. Initial and recurrent tumor distance from the subventricular zone (SVZ) or subgranular zone (SGZ) was measured. Tumors were categorized as NR contacting or non-contacting. The chi-square test was used to analyze the association between tumor contact and recurrence pattern. RESULTS: 49 of 102 (48.0%, 95% CI: 0.386-0.576) tumors contacted NRs at initial presentation, and, of these tumors, 49/49 (100%) contacted NRs at recurrence. Of 53 tumors that were initially non-contacting, 37/53 (69.8%, 95% CI: 0.565-0.804) recurred contacting NRs. In total, 86/102 (84.3%, 95% CI: 0.760-0.901) recurrent GBM contacted NRs compared with 49/102 (48%, 95% CI: 0.386-0.576) at initial presentation. Of the recurrent tumors that did not contact NRs, 16/53 (30.1%, 95% CI: 0.195-0.435) recurred medially toward NRs with a significant decrease in distance between tumor contrast enhancement and NRs. 16/49 (32.6%, 95% CI: 0.212-0.466) initially NR-contacting GBMs recurred out-of field while 7/53 (13.2%, 95% CI: 0.0655-0.248) initially non-contacting recurred out of the radiation treatment field (p=0.0315, Odds ratio: 3.19, 95% CI: 1.18-8.62). CONCLUSIONS: GBM contrast-enhancing recurrence is significantly associated with proximity to NRs. NR-contacting initial tumors were more likely to recur out of radiation treatment fields. PMID- 26276529 TI - Multi-variable models predicting specific patient-reported acute urinary symptoms after radiotherapy for prostate cancer: Results of a cohort study. AB - PURPOSE: A prospective trial started in 2010, aiming at developing models for urinary toxicity and erectile dysfunction after radiotherapy for prostate cancer. This analysis is finalised at highlighting correlations between clinical/dosimetric factors and acute urinary specific symptoms, as measured by single questions of the International Prostate Symptom Score (IPSS). MATERIALS/METHODS: IPSS was prospectively collected before and at the end of radiotherapy; absolute weekly bladder dose-surface histograms (DSHw) were chosen as dosimetric descriptors. Relevant clinical factors were prospectively gathered. Backward feature selection was used to identify variables to be included in logistic models for moderate-severe (scores?4) urinary symptoms. RESULTS: Complete data of 262 patients (120 conventional fractionation, 142 hypofractionation) were available. Smoking was a strong predictor for feeling of incomplete emptying, frequency, intermittency, urgency and straining; neoadjuvant hormonal therapy and use of antihypertensive drugs were risk factors for intermittency and weak stream, respectively. The baseline score was a major predictor for all symptoms with the exception of intermittency. DSHw were correlated to increased risk of frequency, intermittency, urgency and nocturia. Most models showed moderate-high discrimination (AUC~0.60-0.79). CONCLUSIONS: Smoking and other clinical and dosimetric factors predict for specific moderate severe acute urinary symptoms; baseline condition heavily modulated the risk in most endpoints. PMID- 26276528 TI - Patient-reported quality of life after stereotactic body radiotherapy (SBRT), intensity modulated radiotherapy (IMRT), and brachytherapy. AB - BACKGROUND AND PURPOSE: Stereotactic body radiotherapy (SBRT) is being used for prostate cancer, but concerns persist about toxicity compared to other radiotherapy options. MATERIALS AND METHODS: We conducted a multi-institutional pooled cohort analysis of patient-reported quality of life (QOL) [EPIC-26] before and after intensity-modulated radiotherapy (IMRT), brachytherapy, or SBRT for localized prostate cancer. Data were analyzed by mean domain score, minimal clinically detectable difference (MCD) in domain score, and multivariate analyses to determine factors associated with domain scores at 2-years. RESULTS: Data were analyzed from 803 patients at baseline and 645 at 2-years. Mean declines at 2 years across all patients were -1.9, -4.8, -4.9, and -13.3 points for urinary obstructive, urinary incontinence, bowel, and sexual symptom domains, respectively, corresponding to MCD in 29%, 20%, and 28% of patients. On multivariate analysis (vs. IMRT), brachytherapy had worse urinary irritation at 2 years (-6.8 points, p<0.0001) but no differences in other domains (p>0.15). QOL after SBRT was similar for urinary (p>0.5) and sexual domains (p=0.57), but was associated with better bowel score (+6.7 points, p<0.0002). CONCLUSIONS: QOL 2 years after brachytherapy, IMRT, or SBRT is very good and largely similar, with small differences in urinary and bowel QOL that are likely minimized by modern techniques. PMID- 26276530 TI - Conceptualisations and perceptions of the nurse preceptor's role: A scoping review. AB - OBJECTIVES: The practice of nursing is a substantially different undertaking to supervising nursing students. A clear conceptualisation of the preceptor role reveals its scope, expectations and responsibilities. The aim of this scoping review is to investigate what is known in the pertinent literature about preceptors' experiences of their supervision practices and their perceptions of what makes a good workplace environment that enables good preceptorship and is conducive to student learning. DESIGN AND DATA SOURCES: The literature scoping review design by Arksey and O'Malley was adopted for this literature review study because it enables researchers to chart, gather and summarise known literature on a given topic. Databases searched included Scopus, Ebsco, Informit and VOCEDplus. REVIEW METHOD: To answer our research question what is known about how undergraduate nursing student preceptors' supervision practices are conceptualised and perceived we posed four analysis questions to our literature set: (1) How do the articles conceptualise preceptorship? (2) What pedagogical frameworks are used to understand preceptorship? (3) What are the messages for preceptorship practices? (4) What are the recommendations for future research? RESULTS: A total of 25 articles were identified as eligible for this study. The results are ordered into four sections: theoretical conceptualisations of the preceptorship role, pedagogical framework, messages about preceptoring and recommendations for further research. CONCLUSION: The discourse of preceptorship is not underpinned by a strong theoretical and pedagogical base. The role of preceptors has not been expanded to include theoretical perspectives from socio cultural practice and social learning paradigms. PMID- 26276531 TI - The use of reflective journaling as a learning strategy during the clinical rotations of students from the faculty of health sciences: An action-research study. AB - BACKGROUND: Reflective practice contributes significantly to the assimilation of knowledge in undergraduate health students. Reflective journals constitute a learning strategy that promotes student reflection during clinical practice. AIMS: The overall aim of the study was to explore teachers' perceptions and experiences regarding the use of reflective clinical journals as a learning tool for students in order to improve the implementation of clinical journal writing in all the Health Science degrees offered by our University. METHOD: A qualitative research study was performed using the Action-Research method. Students studying various degrees at our Health Faculty were considered for this study (Nursing Physiotherapy, and Physiotherapy and Physical Activity and Sport Science). Data were collected using triangulation of document analysis (102 student journals and 12 teacher journals, together with the teachers' responses to the student's journals) and transcripts from 2 discussion groups (1 student discussion group and 1 teacher discussion group). Data analysis was performed based on the constant comparative method using ATLAS.ti version 6.2 software. RESULTS: Four qualitative themes emerged from the data: the journal as a teaching strategy; building a relationship of trust between the tutor and the student; the role of the teacher and the world of emotions. CONCLUSIONS: Several recommendations for supporting clinical journal writing were identified: an informative meeting should be arranged with students; written guidelines should be provided; a personal interview with the student is recommended at the start of the activity; feedback should be offered over short time periods; teachers should provide constructive feedback; and students should adopt a free writing approach, or be guided by very open questions. Finally, it is important that students be familiarized with the assessment criteria. PMID- 26276532 TI - What deters nurses from participating in web-based graduate nursing programs?: A cross-sectional survey research study. AB - BACKGROUND: A graduate degree is required of nursing faculty in America. Because of the nursing faculty shortage, web-based graduate nursing programs are being offered to encourage nurses to return to school. The identification of deterrents to participating in these programs is an important step in increasing enrollment. OBJECTIVE: To identify deterrents to participation in web-based graduate nursing programs. DESIGN: Descriptive survey research. SETTING: Louisiana PARTICIPANTS: Two hundred and eighty-one registered nurse members of the Louisiana Nurses' Association. METHODS: The 54-item four-point Likert-type interval scale Deterrents to Participation in Web-Based Graduate Nursing Programs Survey Instrument was used. Data were collected over 8weeks using SurveyMonkey.com to administer the web survey tool to all members of the Louisiana State Nurses' Association. RESULTS: A factor analysis revealed a three-factor solution that explained 55.436% of the total variance in deterrents to participation in web based graduate nursing programs. The factors were labeled "concerns about quality, cost, and time," "concerns about access to resources: technological and personal," and "concerns about electronic mediated communication." Multiple regression analysis revealed an overall model of three predictors of deterrents to participation in web-based graduate nursing programs: no computer literacy, annual household income between 20,000 and 50,000 dollars, and having the current educational status of graduating from a diploma RN program. This model accounted for 21% of the variance in the deterrents to participation scores. CONCLUSIONS: Since these three significant predictors of deterrents to participation in web based graduate nursing programs were identified, web-based nursing graduate program administrators might consider an outreach to RN diploma graduates in an effort to make them aware of available technology support programs to foster participation. Scholarships for lower income nursing students are recommended, and programs to support computer literacy within the nursing community should be considered. PMID- 26276533 TI - Modularity of the anthropoid dentition: Implications for the evolution of the hominin canine honing complex. AB - In most anthropoid primates, the maxillary canine, mandibular canine, and mesial mandibular premolar form a functional complex that hones the canines. Characters in functional complexes are predicted to covary genetically, which constrains their evolutionary independence. As a result of substantial changes to canine and honing premolar size and shape, hominins are characterized by the apomorphic loss of canine honing. In early hominins, changes in canine and 'honing' premolar size and shape appear to have been uncoordinated, which is unexpected if there is strong genetic covariation coupling these teeth. Using the pattern and magnitude of phenotypic dental size covariation in extant anthropoids, results of this study indicate that certain dimensions of the anthropoid honing complex are characterized by strong size covariation within species and that canine and honing premolar size have evolved in a coordinated manner in both males and females, which undermines arguments that the complex is selectively important only in males. Further, there is no evidence for negative or strong positive covariance between canine and either incisor or postcanine size. If patterns of phenotypic covariation reflect genetic covariation, this suggests that canine reduction was unlikely to have been a dependent change associated with the development of postcanine megadontia or incisor reduction. PMID- 26276534 TI - Functional aspects of metatarsal head shape in humans, apes, and Old World monkeys. AB - Modern human metatarsal heads are typically described as "dorsally domed," mediolaterally wide, and dorsally flat. Despite the apparent functional importance of these features in forefoot stability during bipedalism, the distinctiveness of this morphology has not been quantitatively evaluated within a broad comparative framework. In order to use these features to reconstruct fossil hominin locomotor behaviors with any confidence, their connection to human bipedalism should be validated through a comparative analysis of other primates with different locomotor behaviors and foot postures, including species with biomechanical demands potentially similar to those of bipedalism (e.g., terrestrial digitigrady). This study explores shape variation in the distal metatarsus among humans and other extant catarrhines using three-dimensional geometric morphometrics (3 DGM). Shape differences among species in metatarsal head morphology are well captured by the first two principal components of Procrustes shape coordinates, and these two components summarize most of the variance related to "dorsal doming" and "dorsal expansion." Multivariate statistical tests reveal significant differences among clades in overall shape, and humans are reliably distinguishable from other species by aspects of shape related to a greater degree of dorsal doming. Within quadrupeds, terrestrial species also trend toward more domed metatarsal heads, but not to the extent seen in humans. Certain aspects of distal metatarsus shape are likely related to habitual dorsiflexion of the metatarsophalangeal joints, but the total morphological pattern seen in humans is distinct. These comparative results indicate that this geometric morphometric approach is useful to characterize the complexity of metatarsal head morphology and will help clarify its relationship with function in fossil primates, including early hominins. PMID- 26276535 TI - NORM in the East Midlands' oil and gas producing region of the UK. AB - Naturally occurring radioactive material (NORM) is a common feature in North Sea oil and gas production offshore but, to date, has been reported from only one production site onshore in the United Kingdom. The latter, Wytch Farm on the Dorset coast, revealed high activity concentrations of (210)Pb in metallic form but little evidence of radium accumulation. NORM has now been discovered at two further onshore sites in the East Midlands region of the UK. The material has been characterized in terms of its mineralogy, bulk composition and disequilibrium in the natural uranium and thorium series decay chains. In contrast to Wytch Farm, scale and sludge samples from the East Midlands were found to contain elevated levels of radium and radioactive progeny associated with crystalline strontiobarite. The highest (226)Ra and (228)Ra activity concentrations found in scale samples were 132 and 60 Bq/g, with mean values of 86 and 40 Bq/g respectively; somewhat higher than the mean for the North Sea and well above national exemption levels for landfill disposal. The two East Midlands sites exhibited similar levels of radioactivity. Scanning electron microscope imaging shows the presence of tabular, idiomorphic and acicular strontiobarite crystals with elemental mapping confirming that barium and strontium are co located throughout the scale. Bulk compositional data show a corresponding correlation between barium-strontium concentrations and radium activity. Scales and sludge were dated using the (226)Ra/(210)Pb method giving mean ages of 2.2 and 3.7 years, respectively. The results demonstrate clearly that these NORM deposits, with significant radium activity, can form over a very short period of time. Although the production sites studied here are involved in conventional oil recovery, the findings have direct relevance should hydraulic fracturing for shale gas be pursued in the East Midlands oilfield. PMID- 26276536 TI - Chemical structure and biological activity of a quorum sensing pheromone from Bacillus subtilis subsp. natto. AB - Bacillus subtilis subsp. natto secrets a peptide pheromone, named ComXnatto pheromone, as an inducer for biofilm formation containing poly-gamma-glutamic acid. Recently, the ComXnatto pheromone was identified to be a hexapeptide with an amino acid sequence of Lys-Trp-Pro-Pro-Ile-Glu, and the tryptophan residue was post-translationally modified with a farnesyl group. In order to determine the precise modification of the tryptophan residue, ComXnatto pheromone was synthesized using solid-phase peptide synthesis. Biological activity of the ComXnatto pheromone was then investigated. It was demonstrated that poly-gamma glutamic acid production were accelerated by ComXnatto pheromone at more than 1 nM in natto. PMID- 26276538 TI - The effect of stricter licensing on road traffic injury events involving 15 to 17 year-old moped drivers in Sweden: A time series intervention study. AB - INTRODUCTION: This study aimed to evaluate and quantify the effect of the introduction of the AM driving license on non-fatal moped-related injuries in Sweden. With the introduction of the new license category in October 2009, prospective moped drivers are now required to pass a mandatory theory test following a practical and theoretical course. In addition, obtaining a license to operate a moped is now considerably more costly. METHODS: Time series intervention analysis on monthly aggregated injury data (1st Jan 2007-31st Dec 2013) was performed using generalized additive models for location, shape and scale (GAMLSS) to quantify the effect size on injury events involving teenage (15 17 years) moped drivers, while controlling for trend and seasonality. Exposure was adjusted for by using the number of registered mopeds in traffic as a proxy. RESULTS: The introduction of AM license was associated with a 41% reduction in the rate of injury events involving 15-year-old moped drivers (IRR 0.59 [95% CI: 0.48-0.72]), and a 39% and 36% decrease in those involving 16-year-old (IRR 0.61 [95% CI: 0.48-0.79]) and 17-year-old drivers (IRR 0.64 [95% CI: 0.46-0.90]), respectively. The effect in the 15-year-old stratum was decreased roughly by half after adjusting for exposure, but remained significant, and the corresponding estimates in the other age groups did not change noticeably. CONCLUSIONS: This study provides quasi-experimental evidence of an effect on non-fatal moped related injuries as a result of stricter licensing rules. Only part of the effect could be explained by a reduction in the number of mopeds in traffic, indicating that other mechanisms must be studied to fully understand the cause of the reduction in injuries. PMID- 26276537 TI - The inhibition of type I bacterial signal peptidase: Biological consequences and therapeutic potential. AB - The general secretory pathway has long been regarded as a potential antibiotic drug target. In particular, bacterial type I signal peptidase (SPase) is emerging as a strong candidate for therapeutic use. In this review, we focus on the information gained from the use of SPase inhibitors as probes of prokaryote biology. A thorough understanding of the consequences of SPase inhibition and the mechanisms of resistance that arise are essential to the success of SPase as an antibiotic target. In addition to the role of SPase in processing secreted proteins, the use of SPase inhibitors has elucidated a previously unknown function for SPase in regulating cleavage events of membrane proteins. PMID- 26276539 TI - Comparative transcriptomic analysis between an artificially induced SIRS in healthy individuals and spontaneous sepsis. AB - Sepsis is defined as a syndrome combining a systemic inflammatory response with a documented infection. It may progress to more serious cases such as septic shock following the failure of one or more organs and the emergence of hemodynamic defects. Assuming that the emergence of serious septic syndromes may be partially explained by the early loss of regulation of the inflammatory response, we decided to compare, in a transcriptomic perspective, the biological mechanisms expressed during an induced systemic inflammatory response with those expressed during severe septic syndromes. By using open-access transcriptomic databases, we first studied the kinetics of an induced inflammatory response. The use of functional analysis helped us identify discriminating biological mechanisms, such as the mTOR signaling pathway, between the pathological cases of sepsis and non pathological (i.e., the artificially induced SIRS) cases. PMID- 26276540 TI - PVDF-Nafion nanomembranes coated microneedles for in vivo transcutaneous implantable glucose sensing. AB - We demonstrate that microporous PVDF membranes sandwiched between multiple layers of nanomaterials can be used for continuous monitoring of glucose level in vivo. This is achieved by coating needle electrodes with Polyaniline nanofiber, Platinum nanoparticles, glucose oxidase enzyme and porous layers, successfully fabricated with layer-by-layer deposition. Nanoparticles incorporated into conductive Polyaniline nanofibers resulted in high surface to volume ratio and electrocatalytic activity for glucose enzyme. A composite coating membrane of porous PVDF and nano-sphere Nafion limited the glucose transportation and increased the lifetime of in vivo measurements. The glucose biosensor exhibited a sub-microamperometric output current, fast response time of less than 30s and a sensitivity of 0.23 MUA/mM. The linear sensing range in terms of glucose concentration was from 0 to 20mM. Implantable experiments using mice models showed excellent response to the variation of blood glucose concentration while maintaining biocompatibility with the surrounding tissues. The sensitivity was shown to remain within 10% close to initial sensitivity within the 7 days of continuous monitoring, and maintain at 70% of the initial sensitivity within 21 days. PMID- 26276542 TI - Silver nanoparticles-enhanced time-resolved fluorescence sensor for VEGF(165) based on Mn-doped ZnS quantum dots. AB - A silver nanoparticles (AgNPs)-enhanced time-resolved fluorescence (TR-FL) sensor based on long-lived fluorescent Mn-doped ZnS quantum dots (QDs) is developed for the sensitive detection of vascular endothelial growth factor-165 (VEGF165), a predominant cancer biomarker in cancer angiogenesis. The aptamers bond with the Mn-doped ZnS QDs and the BHQ-2 quencher-labelling strands hybridized in duplex are coupled with streptavidin (SA)-functionalized AgNPs to form the AgNPs enhanced TR-FL sensor, showing lower fluorescence intensity in the duplex state due to the fluorescence resonance energy transfer (FRET) between the Mn-doped ZnS QDs and quenchers. Upon the addition of VEGF165, the BHQ-2 quencher-labelling strands of the duplex are displaced, leading to the disruption of the FRET. As a result, the fluorescence of the Mn-doped QDs within the proximity of the AgNPs is recovered. The FL signal can be measured free of the interference of short-lived background by setting appropriate delay time and gate time, which offers a signal with high signal-to-noise ratio in photoluminescent biodetection. Compared with the bare TR-FL sensor, the AgNPs-based TR-FL sensor showed a huge improvement in fluorescence based on metal-enhanced fluorescence (MEF) effect, and the sensitivity increased 11-fold with the detection limit of 0.08 nM. In addition, the sensor provided a wide range of linear detection from 0.1 nM to 16 nM. PMID- 26276541 TI - Wearable salivary uric acid mouthguard biosensor with integrated wireless electronics. AB - This article demonstrates an instrumented mouthguard capable of non-invasively monitoring salivary uric acid (SUA) levels. The enzyme (uricase)-modified screen printed electrode system has been integrated onto a mouthguard platform along with anatomically-miniaturized instrumentation electronics featuring a potentiostat, microcontroller, and a Bluetooth Low Energy (BLE) transceiver. Unlike RFID-based biosensing systems, which require large proximal power sources, the developed platform enables real-time wireless transmission of the sensed information to standard smartphones, laptops, and other consumer electronics for on-demand processing, diagnostics, or storage. The mouthguard biosensor system offers high sensitivity, selectivity, and stability towards uric acid detection in human saliva, covering the concentration ranges for both healthy people and hyperuricemia patients. The new wireless mouthguard biosensor system is able to monitor SUA level in real-time and continuous fashion, and can be readily expanded to an array of sensors for different analytes to enable an attractive wearable monitoring system for diverse health and fitness applications. PMID- 26276543 TI - Immunosensing platform based on gallium nanoparticle arrays on silicon substrates. AB - Gallium nanoparticles (GaNPs) of different sizes are deposited on Si(100) substrates by thermal evaporation. Through ellipsometric analysis, it is possible to investigate the plasmonic effects in the GaNPs and exploit them to develop biosensors. The excitation of the resonant modes for certain incidence angles leads to negative values of the imaginary part of the pseudodielectric function () obtained in ellipsometry. Furthermore, there is an abrupt sign change when the difference between the phase shifts of p- and s-polarization components reaches 180 degrees at an energy of around 3.15 eV. At that energy, reversal of the polarization handedness (RPH) occurs for an elliptically polarized input beam. The energy of the RPH condition reduces as the evaporation time increases. The slope of at the RPH condition is extremely sensitive to changes in the surrounding medium of the NP surface and prompts the use of the GaNP/Si system as sensor platform. Fourier transformed infrared spectroscopy (FTIR) is used before and after functionalization with 3,3' dithiodipropionic acid di(N-succinimidyl ester) and a glutathione-specific antibody to confirm the chemical modification of the sample surface. The developed immunosensor is exposed to different concentrations of glutathione (GSH) showing a linear relationship between the slope of the pseudodielectric function at the RPH condition and the GSH concentration. The immunosensor shows a limit of detection of 10nM enabling its use for the detection of low GSH levels in different medical conditions. PMID- 26276544 TI - Production of carbon-13-labeled cadaverine by engineered Corynebacterium glutamicum using carbon-13-labeled methanol as co-substrate. AB - Methanol, a one-carbon compound, can be utilized by a variety of bacteria and other organisms as carbon and energy source and is regarded as a promising substrate for biotechnological production. In this study, a strain of non methylotrophic Corynebacterium glutamicum, which was able to produce the polyamide building block cadaverine as non-native product, was engineered for co utilization of methanol. Expression of the gene encoding NAD+-dependent methanol dehydrogenase (Mdh) from the natural methylotroph Bacillus methanolicus increased methanol oxidation. Deletion of the endogenous aldehyde dehydrogenase genes ald and fadH prevented methanol oxidation to carbon dioxide and formaldehyde detoxification via the linear formaldehyde dissimilation pathway. Heterologous expression of genes for the key enzymes hexulose-6-phosphate synthase and 6 phospho-3-hexuloisomerase of the ribulose monophosphate (RuMP) pathway in this strain restored growth in the presence of methanol or formaldehyde, which suggested efficient formaldehyde detoxification involving RuMP key enzymes. While growth with methanol as sole carbon source was not observed, the fate of 13C methanol added as co-substrate to sugars was followed and the isotopologue distribution indicated incorporation into central metabolites and in vivo activity of the RuMP pathway. In addition, 13C-label from methanol was traced to the secreted product cadaverine. Thus, this synthetic biology approach led to a C. glutamicum strain that converted the non-natural carbon substrate methanol at least partially to the non-native product cadaverine. PMID- 26276545 TI - Direct quantification of fatty acids in wet microalgal and yeast biomass via a rapid in situ fatty acid methyl ester derivatization approach. AB - Accurate determination of fatty acid contents is routinely required in microalgal and yeast biofuel studies. A method of rapid in situ fatty acid methyl ester (FAME) derivatization directly from wet fresh microalgal and yeast biomass was developed in this study. This method does not require prior solvent extraction or dehydration. FAMEs were prepared with a sequential alkaline hydrolysis (15 min at 85 degrees C) and acidic esterification (15 min at 85 degrees C) process. The resulting FAMEs were extracted into n-hexane and analyzed using gas chromatography. The effects of each processing parameter (temperature, reaction time, and water content) upon the lipids quantification in the alkaline hydrolysis step were evaluated with a full factorial design. This method could tolerate water content up to 20% (v/v) in total reaction volume, which equaled up to 1.2 mL of water in biomass slurry (with 0.05-25 mg of fatty acid). There were no significant differences in FAME quantification (p>0.05) between the standard AOAC 991.39 method and the proposed wet in situ FAME preparation method. This fatty acid quantification method is applicable to fresh wet biomass of a wide range of microalgae and yeast species. PMID- 26276546 TI - Treating gynecologic malignancies with selective estrogen receptor downregulators (SERDs): promise and challenges. AB - Endometrial and ovarian cancers are estrogen-dependent gynecologic malignancies. Although many are estrogen receptor (ER) positive, treatment with the selective estrogen receptor modulator (SERM) tamoxifen, a tissue selective partial-agonist, has demonstrated only modest clinical benefit. Selective estrogen receptor downregulators (SERDs) are pure ER antagonists showing a benefit for advanced ER positive breast cancer, which has bolstered their potential use for ER positive gynecologic malignancies. We summarize these preclinical and clinical data, suggesting that a subpopulation of patients with endometrial or ovarian cancer exists in which treatment with SERDs results in improved outcome. However, the full potential of SERDs for a gynecologic malignancies will be realized only when the appropriate predictive biomarkers are identified. Additionally, a further understanding ER signaling in the context of ovarian and endometrial tissues that appear to involve c-Src and other kinase pathways is needed to successfully address the emergence of resistance with rationally designed combination therapies. PMID- 26276547 TI - Hydrophosphination of CO2 and subsequent formate transfer in the 1,3,2 diazaphospholene-catalyzed N-formylation of amines. AB - Hydrophosphination of CO2 with 1,3,2-Diazaphospholene (NHP-H; 1) afforded phosphorus formate (NHP-OCOH; 2) through the formation of a bond between the electrophilic phosphorus atom in 1 and the oxygen atom from CO2 , along with hydride transfer to the carbon atom of CO2 . Transfer of the formate from 2 to Ph2 SiH2 produced Ph2 Si(OCHO)2 (3) in a reaction that could be carried out in a catalytic manner by using 5 mol % of 1. These elementary reactions were applied to the metal-free catalytic N-formylation of amine derivatives with CO2 in one pot under ambient conditions. PMID- 26276548 TI - Measures of satisfaction for providers and patients using same day teledermoscopy consultation. AB - BACKGROUND: We aimed to determine whether patients and providers were satisfied with teledermoscopy consultation for skin lesions. METHODS: From 2010 to 2011, patients with clinically suspicious lesions were referred for teledermoscopy by internal medicine physicians. Lesions were digitally photographed using a dermatoscope accessory lens. Images were interpreted by an on-call dermatologist. We conducted same day surveys of providers and patients after the evaluations. RESULTS: The survey response rate was 100%. Of the 20 patients surveyed, all agreed that a teledermoscopic consult was convenient and helpful. Nineteen patients (95%) strongly agreed that teledermoscopy potentially was a cost-saving tool. All providers thought the evaluations were helpful. Ninety-five percent of providers and patients reported satisfaction with the ease of use of this technology. CONCLUSIONS: Teledermoscopy may give primary care providers the ability to consult with dermatologists when seeing patients in remote or medically underserved areas. This can streamline the referral process and decrease the number of referrals for benign lesions. PMID- 26276549 TI - The lack of a non-communicable disease curriculum threatens the relevance of global public health education. AB - BACKGROUND: Non-communicable diseases (NCDs) such as cardiovascular diseases (CVDs), cancer, lung disease and diabetes are major public health challenges for emerging economies. However, Masters of Public Health (MPH) curricula in the USA do not provide germane coursework. METHODS: To assess the availability of global NCD courses in MPH curricula, we searched the websites of the 50 schools accredited by the Council on Education for Public Health as of 1 July 2013. Our questionnaire queried availability of a global or international health department or track, availability of an NCD track, and the presence of courses on NCD, NCD risk factors, CVD or global NCDs as well as global health infrastructure. RESULTS: All schools had online course coursework available. Thirty-one schools (62%) offered a global/international health track or certificate; 38 (76%) offered an NCD course but only 4 (8%) offered a global NCD course. Of the schools with a global health program, none required an NCD course but all offered courses on global health economics or infrastructure. CONCLUSION: For public health schools to be aligned with global realities and to retain a leadership role, curricular initiatives that highlight the NCD epidemic and its societal complexities will need new emphasis. PMID- 26276550 TI - Assessment of vascular function in Mexican women exposed to polycyclic aromatic hydrocarbons from wood smoke. AB - The use of solid fuels for cooking and heating is likely to be the largest source of indoor air pollution on a global scale; these fuels emit substantial amounts of toxic pollutants such as polycyclic aromatic hydrocarbons (PAHs) when used in simple cooking stoves (such as open "three-stone" fires). Moreover, indoor air pollution from biomass fuels is considered an important risk factor for human health. The aim of this study was to evaluate the relationship between exposure to PAHs from wood smoke and vascular dysfunction; in a group of Mexican women that use biomass combustion as their main energy source inside their homes. We used 1-hydroxypyrene (1-OHP) as an exposure biomarker to PAHs and it was assessed using high performance liquid chromatography. The endothelium-dependent vasodilation was assessed through a vascular reactivity compression test performed with a pneumatic cuff under visualization of the brachial artery using high resolution ultrasonography (HRU). Assessment of the carotid intima-media thickness (CIMT) was used as an atherosclerosis biomarker (also assessed using HRU); and clinical parameters such as anthropometry, blood pressure, glucose, triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol, among others were also evaluated. The mean concentration of urinary 1-OHP found in exposed women was 0.46+/-0.32MUmol/mol Cr (range: 0.086-1.23MUmol/mol Cr). Moreover, vascular dysfunction (diminished endothelium dependent vasodilation) was found in 45% of the women participating in the study. Association between vascular function and 1-OHP levels was found to be significant through a logistic regression analysis (p=0.034; r(2)=0.1329). Furthermore, no association between CIMT and clinical parameters, urinary 1-OHP levels or vascular dysfunction was found. Therefore, with the information obtained in this study, we advocate for the need to implement programs to reduce the risk of exposure to PAHs in communities that use biomass fuels as a main energy source. PMID- 26276553 TI - Effects of Anesthesia Type on Perioperative Outcome After Endovascular Aneurysm Repair. AB - PURPOSE: To examine outcomes of endovascular aortic aneurysm repair (EVAR) using general, regional, or local anesthesia. METHODS: From March 2009 to April 2011, patients were enrolled from 79 sites in 30 countries worldwide and treated with an Endurant Stent Graft System. Data were compared among 3 groups based on the method of anesthesia: general anesthesia (GA) was used in 785 (62%) patients, regional anesthesia (RA) in 331 (27%) patients, and local anesthesia (LA) in 145 (11%) patients. Multivariate logistic regression analysis was performed to adjust for possible confounding factors; outcomes are presented as the odds ratio and 95% confidence interval. RESULTS: There were intercontinental differences in the distribution of type of anesthesia used for EVAR. Higher ASA (American Society of Anesthesiologists) classification was associated with predominant use of GA. Procedure time was reduced in LA (80.4+/-40.0 minutes) compared with RA (94.2+/ 41.6 min, adjusted p=0.001) and GA (105.3+/-46.0 minutes, adjusted p<0.001). Intensive care unit (ICU) admission was less frequent for RA than for GA (adjusted OR 0.71, 95% CI 0.53 to 0.97, p=0.030) and LA (adjusted OR 0.51, 95% CI 0.33 to 0.79, p=0.002). Postoperative hospital stay was significantly shorter for RA and LA compared with GA (adjusted p=0.003 and p=0.010, respectively). There were no significant differences in systemic and surgical complications. Mortality rates within 30 days did not differ among the groups. CONCLUSION: Type of anesthesia used during EVAR has no influence on perioperative mortality and morbidity. The use of local or regional anesthesia during EVAR appeared to be beneficial concerning procedure time, ICU admission, and postoperative hospital stay. PMID- 26276552 TI - Predictors of 2-Year Mortality and Risk Stratification After Surgical or Endovascular Revascularization of Infrainguinal Artery Disease in Hemodialysis Patients With Critical Limb Ischemia. AB - PURPOSE: To examine the 2-year mortality in hemodialysis (HD) patients with critical limb ischemia (CLI) and determine predictors that may aid in the selection of a revascularization strategy [bypass surgery or endovascular therapy (EVT)] according to current guidelines. METHODS: From 2007 to 2009, 246 consecutive CLI patients (mean age 69+/-10 years; 170 men) on HD underwent revascularization for de novo infrainguinal lesions (178 EVT and 68 bypass grafting). The majority of the patients had diabetes (170, 69%) and tissue loss (194, 79%); nearly half (111, 45%) were nonambulatory. Overall survival after revascularization was estimated by Kaplan-Meier analysis. Predictors for 2-year mortality after revascularization were determined using a Cox proportional hazards model; results are given as the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Overall survival rate was 77% at 1 year and 66% at 2 years. Predictors of 2-year mortality after revascularization were age >75 years (HR 1.82, 95% CI 1.14 to 2.91, p=0.012), albumin <3 g/dL (HR 2.31, 95% CI 1.39 to 3.84, p=0.001), and ejection fraction <50% (HR 1.73, 95% CI 1.06 to 2.83, p=0.027). Patients with more predictors had a higher incidence of death within 2 years after revascularization. CONCLUSION: Advanced age, low albumin level, and low ejection fraction were independently associated with 2-year mortality after revascularization in HD patients with CLI. Risk stratification by these factors would be useful for deciding on a revascularization strategy. PMID- 26276554 TI - Through-Plane Movement at Multiple Aortic Levels on Dynamic Computed Tomography Angiography Is Limited in Patients With an Abdominal Aortic Aneurysm. AB - PURPOSE: To analyze the movement of the aorta in the craniocaudal direction (through-plane movement) during the cardiac cycle at several levels to determine any potential impact on endovascular aneurysm repair (EVAR) of abdominal aortic aneurysm (AAA). METHODS: For this study, 30 patients (median age 73.0 years; 27 men) with an infrarenal AAA were randomly selected from a prospectively maintained EVAR database. All patients had undergone preoperative electrocardiogram-gated computed tomography angiography consisting of 8 phases. After semiautomatic segmentation, a 3-dimensional location probe was placed in the center of the aorta (center point) on the orthogonal slices at 12 different levels along the aorta and iliac arteries for all 8 phases. Movement of the center point during the cardiac cycle was analyzed for each level. Values are given as the median and interquartile range (IQR). RESULTS: The median through plane movement of all levels was 3.0 mm (IQR 2.8-3.2) and appeared to be lower in the region of the celiac and renal arteries: 2.6 mm (IQR 1.7-3.1) at 3 cm proximal to the most distal renal artery and 2.4 mm (IQR 1.9-2.9) at 1 cm distal to the most distal renal artery, respectively. The thoracic part of the aorta showed the largest through-plane motion: 4.1 mm (IQR 2.7-4.6). CONCLUSION: This study quantifies aortic through-plane motion in the craniocaudal direction. Since through-plane movement appears to be limited, findings of previous studies investigating pulsatile in-plane distension seem to be representative for aortic distension. PMID- 26276551 TI - Subclinical and clinical hypothyroidism and non-alcoholic fatty liver disease: a cross-sectional study of a random population sample aged 18 to 65 years. AB - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common disorders of the liver worldwide. Recently, a correlation between thyroid dysfunction and NAFLD has been discussed. Objective of the present study was to investigate the association between thyroid dysfunction and hepatic steatosis. METHODS: Data from 2,445 subjects (51.7% females) aged 18 to 65 years participating in a population-based cross-sectional study were assessed based on a standardized questionnaire and documentation of physical, biochemical and ultrasonographic findings. After application of exclusion criteria, a total of 1,276 subjects were included in the study collective. The influence of potential factors on the development of hepatic steatosis was assessed using multivariate logistic regression. RESULTS: The prevalence of hepatic steatosis in the study collective was 27.4% (n = 349). The serum thyroxin (TT4) concentration in subjects with hepatic steatosis was reduced (p =0.0004). Adjusting for age, or BMI, there was an increased prevalence of hepatic steatosis in subjects with reduced TT4 concentrations (p = 0.0143; p = < .0001). CONCLUSIONS: The findings of the present study confirm an association between both subclinical and clinical hypothyroidism and hepatic steatosis. PMID- 26276555 TI - Chronic black tea extract consumption improves endothelial function in ovariectomized rats. AB - PURPOSE: Menopause escalates the risk of cardiovascular diseases in women. There is an unmet need for better treatment strategy for estrogen-deficiency-related cardiovascular complications. Here we investigated the impact of chronic black tea extract (BT) consumption on cardiovascular function and lipid metabolism using a rat model of estrogen deficiency. METHODS: Female Sprague-Dawley rats were ovariectomized (OVX) and treated with BT (15 mg/kg/day, 4 weeks; active ingredients: theaflavins) or estrogen (E2) treatment for 4 weeks. Serum was collected for measuring cholesterol, triacylglycerol and estradiol levels. Changes in vascular reactivity were examined. The protein levels of NADPH oxidases were assessed by Western blotting. Reactive oxygen species (ROS) level was measured using dihydroethidium fluorescence imaging. The concentrations of cGMP were measured using ELISA kit. RESULTS: Aortic rings from control, BT treated and E2-treated OVX rats exhibited a greater increase in Phe-induced contraction after inhibition of NO synthase compared with those from OVX rats. ACh-induced endothelium-dependent relaxations were augmented in aortae and renal arteries in BT/E2-treated OVX rats than in OVX rats. BT/E2 treatment improved flow-mediated dilatation in small mesenteric resistance arteries of OVX rats. BT/E2 treatment restored the eNOS phosphorylation level and reversed the up regulation of NADPH oxidases and ROS overproduction in OVX rat aortae. ACh stimulated cGMP production was significantly elevated in the aortae from BT- and E2-treated rats compared with those from OVX rats. BT/E2 treatment reduced circulating levels of total cholesterol. CONCLUSIONS: The present study reveals the novel benefits of chronic BT consumption to reverse endothelial dysfunction and favorably modifying cholesterol profile in a rat model of estrogen deficiency and provides insights into developing BT as beneficial dietary supplements for postmenopausal women. PMID- 26276556 TI - A multi-centre pilot study of iodine status in UK schoolchildren, aged 8-10 years. AB - PURPOSE: Iodine, as an essential constituent of thyroid hormones, is required for brain development. Iodine status is low in some UK population groups, notably in teenage girls, women of childbearing age and pregnant women. We aimed to assess iodine status of UK schoolchildren as there are no data on children below 14 years of age. METHODS: Children (boys and girls) aged 8-10 years were recruited to a cross-sectional study from schools in three areas of the UK (Omagh, Northern Ireland; Glasgow, Scotland, and Guildford, South-East England). Spot urine samples, for measurement of urinary iodine concentration, were collected in the winter months (November 2012 to March 2013) and in the summer, in Omagh only (September 2013). A food frequency questionnaire was completed. RESULTS: A total of 168 schoolchildren provided 165 urine samples. The median urinary iodine concentration was 161 ug/L in winter samples (n = 134) and 127 ug/L in summer samples (n = 31). The median urinary iodine concentration for the whole group was 144 ug/L, weighted to account for the unequal proportion of samples from the two seasons. The children are classified as iodine-sufficient by WHO criteria (100 199 ug/L), even in the summer. Milk intake was positively associated with iodine status. CONCLUSIONS: This pilot study suggests that iodine deficiency is unlikely to be a problem in UK children aged 8-10 years. This could be a result of higher intake of milk, the principal UK dietary iodine source, in this age group than in teenagers and adults. Further assessment of iodine status in a representative sample of UK schoolchildren is required. PMID- 26276557 TI - A consistent S-Adenosylmethionine force field improved by dynamic Hirshfeld-I atomic charges for biomolecular simulation. AB - S-Adenosylmethionine (AdoMet) is involved in many biological processes as cofactor in enzymes transferring its sulfonium methyl group to various substrates. Additionally, it is used as drug and nutritional supplement to reduce the pain in osteoarthritis and against depression. Due to the biological relevance of AdoMet it has been part of various computational simulation studies and will also be in the future. However, to our knowledge no rigorous force field parameter development for its simulation in biological systems has been reported. Here, we use electronic structure calculations combined with molecular dynamics simulations in explicit solvent to develop force field parameters compatible with the AMBER99 force field. Additionally, we propose new dynamic Hirshfeld-I atomic charges which are derived from the polarized electron density of AdoMet in aqueous solution to describe its electrostatic interactions in biological systems. The validation of the force field parameters and the atomic charges is performed against experimental interproton NOE distances of AdoMet in aqueous solution and crystal structures of AdoMet in the cavity of three representative proteins. PMID- 26276560 TI - Bone Health and Pelvic Radiotherapy. AB - Survivors who have received pelvic radiotherapy make up many of the long-term cancer population, with therapies for gynaecological, bowel, bladder and prostate malignancies. Individuals who receive radiotherapy to the pelvis as part of their cancer treatment are at risk of insufficiency fractures. Symptoms of insufficiency fractures include pelvic and back pain and immobility, which can affect substantially quality of life. This constellation of symptoms can occur within 2 months of radiotherapy up to 63 months post-treatment, with a median incidence of 6-20 months. As a condition it is under reported and evidence is poor as to the contributing risk factors, causation and best management to improve the patient's bone health and mobility. As radiotherapy advances, chronic symptoms, such as insufficiency fractures, as a consequence of treatment need to be better understood and reviewed. This overview explores the current evidence for the effect of radiotherapy on bone health and insufficiency fractures and identifies what we know and where gaps in our knowledge lie. The overview concludes with the need to take seriously complaints of pelvic pain from patients after pelvic radiotherapy and to investigate and manage these symptoms more effectively. There is a clear need for definitive research in this field to provide the evidence-based guidance much needed in practice. PMID- 26276558 TI - Influence of Alpha and Gamma-Iron Oxide Nanoparticles on Marine Microalgae Species. AB - The effects of alpha-iron oxide (alpha-Fe2O3) and gamma-iron oxide (gamma-Fe2O3) nanoparticles (NPs) on marine microalgae species (Nannochloropsis sp. and Isochrysis sp.) were investigated in this study. Both Fe2O3 NPs covered the surface of algae with the agglomerates of the nanoparticles. This form of physical NP toxicity significantly decreased the sizes of phytoplankton. Both NPs were toxic to the tested algal species, while alpha-Fe2O3 showed less toxicity than gamma-Fe2O3 NPs for both algal species. A comparative analysis of growth data of the two algal species treated with alpha-Fe2O3 or gamma-Fe2O3 NPs revealed that Isochrysis sp. are more sensitive than Nannochloropsis sp. Toxicity of these widely used NPs to primary producers forming the base of the food chain in aquatic environments might result in widespread adverse effects on aquatic environmental health. PMID- 26276559 TI - Prediction of basal metabolic rate in overweight/obese and non-obese subjects and its relation to pulmonary function tests. AB - BACKGROUND: Few studies investigated the association between basal metabolic rate (BMR) and indicators of pulmonary function. This study was conducted to estimate BMR in overweight/obese and non-obese healthy subjects using four commonly used predictive equations and to investigate its relation to the indicators of lung function tests (LFT). A cross sectional study was conducted in Tabuk University, Tabuk, Saudi Arabia. A total of 201 students (98 males and 103 females) participated in the study. Four different values of BMR were calculated for each participant using four different predictive equations (Harris-Benedict, Mifflin, FAO/WHO/UNU and Henry-Rees). A portable All-flow spirometer (Clement Clarke International, Harlow, UK) was used for measurements of LFT. RESULTS: Significantly higher values of spirometric indicators (p < 0.05) were found in males compared to females, except for FEF75 and FEF75-85. Mean BMR values predicted with the four equations were significantly higher in the males compared to the females and among the overweight/obese compared to the non-obese subjects (p < 0.05). The relation between mean BMR values and the indicators of LFT was statistically insignificant (p > 0.05). CONCLUSION: Mean values of LFT indicators are not related to the estimated values of BMR. A practical calculation of BMR based on direct measurement of oxygen consumption is recommended to confirm the absence of this association. PMID- 26276561 TI - 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (DIMBOA) inhibits trichothecene production by Fusarium graminearum through suppression of Tri6 expression. AB - Fusarium head blight (FHB) is a devastating disease of wheat (Triticum aestivum L.) caused by a mycotoxigenic fungus Fusarium graminearum resulting in significantly decreased yields and accumulation of toxic trichothecenes in grains. We tested 7 major secondary metabolites from wheat for their effect on trichothecene production in liquid cultures of F. graminearum producing trichothecene 15-acetyldeoxynivalenol (15-ADON). 2,4-Dihydroxy-7-methoxy-2H-1,4 benzoxazin-3(4H)-one (DIMBOA) benzoxazinoid completely abolished toxin production without any apparent effect on fungal growth. DIMBOA strongly affected the expression of Tri6, encoding a major transcriptional regulator of several genes of the trichothecene biosynthesis pathway. DIMBOA also repressed expression of Tri5, encoding trichodiene synthase, the first enzyme in the trichothecene biosynthesis pathway. Thus, DIMBOA could play an important role against the accumulation of trichothecenes in wheat grain. Breeding or engineering of wheat with increased levels of benzoxazinoids could provide varieties with increased resistance against trichothecene contamination of grain and lower susceptibility to FHB. PMID- 26276562 TI - [Why screen for lung cancer in patients with arterial disease?]. AB - Lung cancer remains the leading cause of cancer death in France. Such a prognosis is explained by late diagnosis at a metastatic stage for half of the patients. Tobacco is the main risk factor for lung cancer, as it is for peripheral arterial disease. A review of literature shows that between 2.3% and 19% of patients with arterial disease also have lung cancer. When lung cancer is detected after treatment of arterial disease, it is at an advanced stage. But it can be diagnosed at an early stage when it is searched simultaneously with arterial disease treatment. There is no recommendation for lung cancer screening specifically for patients with arterial disease. However individual screening based on an annual low-dose chest scan is proposed for smokers meeting the criteria defined by the study of the National Lung Screening Trial (NLST). Such screening has two disadvantages : the high number of false positives and the irradiation induced by the accumulation of examinations. The ISET method would alternatively help to identify circulating tumor cells on a simple blood test for subjects not yet at solid tumor stage, provided this method be subject to multicentric validation. Thus one could consider that the management of a patient with arterial disease meeting NLST criteria should be accompanied with screening for lung cancer by searching for tumor cells associated with low-dose scanner. PMID- 26276563 TI - Arsenic Trioxide Attenuates NF-kappaB and Cytokine mRNA Levels in the Livers of Cocks. AB - Arsenic (As) is a trace element widely found in nature. It exists in several forms, including organic arsenic, inorganic arsenic, and trivalent arsenic, the most toxic. Arsenic trioxide (As2O3) is widespread in nature. This form tends to accumulate in animals and humans and therefore has a potential harm for them. Cytokines play essential roles in the immune response and inflammation. Although the importance of cytokines in the responses to arsenic exposure has been demonstrated in many types of mammals, the function of these in poultry, especially in chickens, remains unclear. The purpose of the present study was to examine the effect of As2O3 exposure on cytokines in cock livers. In this study, 72 1-day-old male Hy-line cocks were randomly divided into four groups including the control group, low-As group, middle-As group, and high-As group. The livers were collected on days 30, 60, and 90 of the experiment. The levels of nuclear factor-kappa B (NF-kappaB), tumor necrosis factor-alpha (TNF-alpha), interleukin 4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-12 beta (IL 12beta), and interleukin-1 beta (IL-1beta) mRNA in the livers of the cocks were measured using real-time PCR. The results showed that the expression levels of IL 6, IL-8, TNF-alpha, and NF-kappaB which seemed to be a critical mediator in the inflammatory response tended to increase in the birds chronically treated with As2O3. However, the mRNA expression levels of IL-4, IL-12beta, and IL-1beta were decreased in the experiment. The information regarding the effects of As2O3 on cytokine mRNA expression generated in this study will be important information for arsenic toxicology evaluation. PMID- 26276564 TI - Mechanisms of Intracellular Calcium Homeostasis in MC3T3-E1 Cells and Bone Tissues of Sprague-Dawley Rats Exposed to Fluoride. AB - Calcium homeostasis of osteoblasts (OBs) has an important role in the physiology and pathology of bone tissue. In order to study the mechanisms of intracellular calcium homeostasis, MC3T3-E1 cells and Sprague-Dawley rats were treated with different concentrations of fluoride. Then, we examined intracellular-free calcium ion ([Ca(2+)]i) in MC3T3-E1 cells as well as mRNA and protein levels of Cav1.2, the main subunit of L-type voltage-dependent calcium channels (VDCCs), Na(+)/Ca(2+) exchange carriers (NCS), and plasma membrane Ca(2+)-ATPase (PMCA), inositol 1,4,5-trisphosphate receptor (IP3R) channels, sarco/endoplasmic reticulum calcium ATPase 2b (SERCA2b)/ATP2A2 in vitro, and rat bone tissues in vivo. Our results showed that [Ca(2+)]i of fluoride-treated OBs increased in a concentration-dependent manner with an increase in the concentration of fluoride. We also found that the low dose of fluoride led to high expression levels of Cav1.2, NCS-1, and PMCA and low expression levels of IP3R and SERCA2b/ATP2A2, while the high dose of fluoride induced an increase in SERCA2b/ATP2A2 levels and decrease in Cav1.2, PMCA, NCS-1, and IP3R levels. These results demonstrate that calcium channels and calcium pumps of plasma and endoplasmic reticulum (ER) membranes keep intracellular calcium homeostasis by regulating Cav1.2, NCS-1, PMCA, IP3R, and SERCA2b/ATP2A2 expression. PMID- 26276565 TI - Time and Concentration-Dependent Therapeutic Potential of Silver Nanoparticles in Cervical Carcinoma Cells. AB - Silver nanoparticles (AgNPs) have well-known anti-bacterial properties and have been widely used in daily life as various medical and general products. There is limited information available on the cytotoxicity of AgNPs. Therefore, the present study aimed to investigate the cytotoxicity of AgNPs in HeLa cells. Cytotoxicity and apoptosis have been observed in the AgNPs treated in the HeLa cells. Sulphorhodamine-B assay (SRB assay) showed the cytotoxic effect in the AgNP-treated HeLa cells. Inverted microscope, fluorescence microscope, and confocal laser scanning microscope (CLSM) analyses showed the apoptosis-induced morphological changes such as rounding in shape, nuclear fragmentation, cytoplasm reduction, loss of adhesion, and reduced cell volume. Necrosis and apoptosis were observed in the AgNP-treated HeLa cells by DNA fragmentation study. Mitochondria derived reactive oxygen species (ROS) have increased in AgNP-treated HeLa cells. Up-regulation of messenger RNA (mRNA) expression of p53, bax, and caspase 3 were found in AgNP-treated HeLa cells. Caspase 3 enzyme activity was found to increase in AgNP-treated HeLa cells. The AgNPs showed the right cytotoxic effect in cervical carcinoma cells. Our results suggest that metal-based nanoparticles might be a potential candidate for the treatment of cervical cancer. PMID- 26276566 TI - Analysis of B-Raf[Formula: see text] inhibitors using 2D and 3D-QSAR, molecular docking and pharmacophore studies. AB - In the present work, a molecular modeling study was carried out using 2D and 3D quantitative structure-activity relationships for the various series of compounds known as B-Raf[Formula: see text] inhibitors. For 2D-QSAR analysis, a linear model was developed by MLR based on GA-OLS with appropriate results [Formula: see text], which was validated by several external validation techniques. To perform a 3D-QSAR analysis, CoMFA and CoMSIA methods were used. The selected CoMFA model could provide reliable statistical values [Formula: see text] based on the training set in the biases of the selected alignment. Using the same selected alignment, a statistically reliable CoMSIA model, out of thirty-one different combinations, was also obtained [Formula: see text]. The predictive accuracy of the derived models was rigorously evaluated with the external test set of nineteen compounds based on several validation techniques. Molecular docking simulations and pharmacophore analyses were also performed to derive the true conformations of the most potent inhibitors with B-Raf[Formula: see text] kinase. PMID- 26276567 TI - Comparison of adaptive statistical iterative and filtered back projection reconstruction techniques in quantifying coronary calcium. AB - BACKGROUND: Adaptive statistical iterative reconstruction (ASIR) has been used to reduce radiation dose in cardiac computed tomography. However, change of image parameters by ASIR as compared to filtered back projection (FBP) may influence quantification of coronary calcium. OBJECTIVE: To investigate the influence of ASIR on calcium quantification in comparison to FBP. METHODS: In 352 patients, CT images were reconstructed using FBP alone, FBP combined with ASIR 30%, 50%, 70%, and ASIR 100% based on the same raw data. Image noise, plaque density, Agatston scores and calcium volumes were compared among the techniques. RESULTS: Image noise, Agatston score, and calcium volume decreased significantly with ASIR compared to FBP (each P < 0.001). Use of ASIR reduced Agatston score by 10.5% to 31.0%. In calcified plaques both of patients and a phantom, ASIR decreased maximum CT values and calcified plaque size. CONCLUSION: In comparison to FBP, adaptive statistical iterative reconstruction (ASIR) may significantly decrease Agatston scores and calcium volumes. PMID- 26276568 TI - The major acute phase proteins of bovine milk in a commercial dairy herd. AB - BACKGROUND: Milk acute phase proteins (APP) have been identified and show promise as biomarkers of mastitis. However analysis of their profile in dairy cows from a production herd is necessary in order to confirm their benefits in mastitis diagnosis. The profiles of milk haptoglobin (Hp), mammary associated serum amyloid A3 (M-SAA3) and C-reactive protein (CRP) were determined in 54 composite milk (milk from all functional quarters of a cow's udder collected in a common receptacle) samples (CMS) from a commercial dairy farm. Milk Hp was also determined in individual quarter milk (milk from a single udder quarter) samples (QMS) (n = 149) of the cows. An ELISA was developed and validated for the determination of milk Hp while commercial kits were used for M-SAA3 and CRP assay respectively. Composite milk APP results were compared with cow factors including parity, stage of lactation, percentage protein and fat as well as somatic cell counts (SCC). RESULTS: Composite milk Hp ranged from <0.4-55 MUg/ml with a median of 3.5 MUg/ml; composite milk M-SAA3 ranged from <0.6-50 MUg/ml and had a median of 1.2 MUg/ml, while CRP ranged from <1.80-173 ng/ml and had a median of 24.6 ng/ml. Significant correlations were found between composite SCC and Hp (P-value <0.009) as well as parity and Hp (P < 0.009), but not between M-SAA3 and SCC, M SAA3 and Hp, M-SAA3 and CRP or M-SAA3 and parity. Milk CRP was correlated with % fat (P = 0.002) and % protein (P = 0.001) of the milk samples. The lack of correlation of SCC with the M-SAA3 and CRP could result from these APP being more sensitive to intra-mammary infection than SCC. Quarter milk Hp had a range of <0.4-420 MUg/ml with a median value of 3.6 MUg/ml, with 92 % of samples below 20 MUg/ml. CONCLUSION: Baseline values of Hp, M-SAA3 and CRP were established in composite milk from cows with normal SCC on the dairy farm. Parity was recognized as a possible confounding factor when diagnosing mastitis using Hp. The value of the APP, Hp, M-SAA3 and CRP as substitutes or to complement SCC in indicating udder inflammation, was demonstrated. PMID- 26276569 TI - What are effective strategies for the implementation of care bundles on ICUs: a systematic review. AB - BACKGROUND: Care bundles have proven to be effective in improving clinical outcomes. It is not known which strategies are the most effective to implement care bundles. A systematic review was conducted to determine the strategies used to implement care bundles in adult intensive care units and to assess the effects of these strategies when implementing bundles. METHODS: The databases MEDLINE/PubMed, Ovid/Embase, CINAHL and CENTRAL were searched for eligible studies until January 31, 2015. Studies with (non)randomised designs on central line, ventilator or sepsis bundles were included if implementation strategies and bundle compliance were reported. Methodological quality was assessed by using the Downs and Black checklist. Data extraction and quality assessments were independently performed by two reviewers. RESULTS: In total, 1533 records were screened and 47 studies were finally included. In 49 %, pre/post designs were used, 38 % prospective cohorts, and the remaining studies used retrospective designs (6 %), interrupted time series (4 %) and longitudinal designs (2 %). The methodological quality was classified as 'fair' in 77 %, and the remaining as 'good' (13 %) and 'poor' (11 %). The most frequently used strategies were education (86 %), reminders (71 %) and audit and feedback (63 %). Our results show that compliance is influenced by multiple factors, i.e. types and numbers of elements varied and different compliance measurements were reported. Furthermore, compliance was calculated within different time frames. Also, detailed information about compliance, such as numerators and denominators, was not reported. Therefore, recalculation of consistent monthly compliance levels was not possible. CONCLUSIONS: The three most frequently used strategies were education, reminders and audit and feedback. We conclude that the heterogeneity among the included studies was high due to the variety in study designs, number and types of elements and types of compliance measurements. Due to the heterogeneity of the data and the poor quality of the studies, conclusions about which strategy results in the highest levels of bundle compliance could not be determined. We strongly recommend that studies in quality improvement should be reported in a formalised way in order to be able to compare research findings. It is imperative that authors follow the standards for quality improvement reporting excellence (SQUIRE) guidelines whenever they report quality improvement studies. PMID- 26276570 TI - Systems biology study of mucopolysaccharidosis using a human metabolic reconstruction network. AB - Mucopolysaccharidosis (MPS) is a group of lysosomal storage diseases (LSD), characterized by the deficiency of a lysosomal enzyme responsible for the degradation of glycosaminoglycans (GAG). This deficiency leads to the lysosomal accumulation of partially degraded GAG. Nevertheless, deficiency of a single lysosomal enzyme has been associated with impairment in other cell mechanism, such as apoptosis and redox balance. Although GAG analysis represents the main biomarker for MPS diagnosis, it has several limitations that can lead to a misdiagnosis, whereby the identification of new biomarkers represents an important issue for MPS. In this study, we used a system biology approach, through the use of a genome-scale human metabolic reconstruction to understand the effect of metabolism alterations in cell homeostasis and to identify potential new biomarkers in MPS. In-silico MPS models were generated by silencing of MPS-related enzymes, and were analyzed through a flux balance and variability analysis. We found that MPS models used approximately 2286 reactions to satisfy the objective function. Impaired reactions were mainly involved in cellular respiration, mitochondrial process, amino acid and lipid metabolism, and ion exchange. Metabolic changes were similar for MPS I and II, and MPS III A to C; while the remaining MPS showed unique metabolic profiles. Eight and thirteen potential high-confidence biomarkers were identified for MPS IVB and VII, respectively, which were associated with the secondary pathologic process of LSD. In vivo evaluation of predicted intermediate confidence biomarkers (beta hexosaminidase and beta-glucoronidase) for MPS IVA and VI correlated with the in silico prediction. These results show the potential of a computational human metabolic reconstruction to understand the molecular mechanisms this group of diseases, which can be used to identify new biomarkers for MPS. PMID- 26276571 TI - Correlation of cumulus gene expression of GJA1, PRSS35, PTX3, and SERPINE2 with oocyte maturation, fertilization, and embryo development. AB - BACKGROUND: GJA1 and PTX3 were proposed as gene markers for oocyte and embryo developmental competence, while SERPINE2 was reported to be associated with pregnancy outcome. PRSS35, which is exclusively expressed in the ovary, may be correlated with oocyte competence. This study was conducted to evaluate the correlation of cumulus GJA1, PRSS35, PTX3, and SERPINE2 gene expression levels with oocyte maturation, fertilization, and early embryo development. METHODS: In total, 308 cumulus cell samples separated from individual cumulus-oocyte complex were obtained from 40 patients undergoing the intracytoplasmic sperm injection treatment procedure. Gene expression levels (mRNA levels) in cumulus cells were assessed using quantitative real-time polymerase chain reaction. RESULTS: Gene expression levels of GJA1 and SERPINE2 in cumulus cells surrounding mature oocytes were significantly lower than those in cumulus cells enclosing immature oocytes. PRSS35 mRNA levels in cumulus cells of fertilized oocytes were significantly higher than those in cumulus cells of unfertilized oocytes. GJA1 and SERPINE2 seemed to express higher mRNA levels, while PRSS35 showed lower expression in cumulus cells of oocytes that developed into embryos with good morphology; however, the expression levels of all three genes and PTX3 showed no significant differences between embryos with good or poor morphology. CONCLUSIONS: GJA1 and SERPINE2 represent potential gene markers associated with oocyte maturation. PRSS35 may be correlated with oocyte fertilization potential. However, GJA1, PRSS35, PTX3, and SERPINE2 may not be considered as marker genes for predicting embryo morphology. PMID- 26276572 TI - Factors Associated With Early Improvement in Low Back Pain After Total Hip Arthroplasty: A Multi-Center Prospective Cohort Analyses. AB - This study identified factors associated with an improvement in low back pain (LBP) at six-month follow-up after total hip arthroplasty (THA). Data from a national registry of 3054 patients were analyzed. Factors under analysis included demographics, comorbid conditions, operative and nonoperative joint pain severity, physical function, and mental health. Differences in these factors between patients with and without improvement in LBP were examined. Among patients reporting severe or moderate LBP preoperatively, 56% improved 6 months after surgery. Patients without improvement were more likely to be on Medicare, have a high school education or less, have household income less than $45,000 and have one or more comorbid conditions. Patients with improvement in LBP experienced more resolution of pain in both the operative and nonoperative hip. PMID- 26276573 TI - Postural and Chronological Change in Pelvic Tilt Five Years After Total Hip Arthroplasty in Patients With Developmental Dysplasia of the Hip: A Three Dimensional Analysis. AB - The pelvis generally tilts to the posterior with movement from the supine to standing position, and with time after total hip arthroplasty (THA). This study aimed to investigate changes in pelvic tilt from the preoperative supine position to the standing position at 5 years after THA (pelvic change, PC). We measured pelvic tilt using a 2D-3D matching technique in 77 unilaterally affected patients who underwent primary THA. PC in 8% of all patients was <=-20 degrees , and the greatest PC was -25 degrees . In these patients, posterior pelvic tilt continued up to 5 years after THA. These patients were older, and their lumbo-lordotic angle was small. For such cases, cup orientation should be planned to account for continuous posterior change in pelvic tilt after THA. PMID- 26276574 TI - National Trends of Simple Prostatectomy for Benign Prostatic Hyperplasia With an Analysis of Risk Factors for Adverse Perioperative Outcomes. AB - OBJECTIVE: To examine the national trends of simple prostatectomy (SP) for benign prostatic hyperplasia (BPH) focusing on perioperative outcomes and risk factors for complications. METHODS: The National Inpatient Sample (2002-2012) was utilized to identify patients with BPH undergoing SP. Analysis included demographics, hospital details, associated procedures, and operative approach (open, robotic, or laparoscopic). Outcomes included complications, length of stay, charges, and mortality. Multivariate logistic regression was used to determine the risk factors for perioperative complications. Linear regression was used to assess the trends in the national annual utilization of SP. RESULTS: The study population included 35,171 patients. Median length of stay was 4 days (interquartile range 3-6). Cystolithotomy was performed concurrently in 6041 patients (17%). The overall complication rate was 28%, with bleeding occurring most commonly. In total, 148 (0.4%) patients experienced in-hospital mortality. On multivariate analysis, older age, black race, and overall comorbidity were associated with greater risk of complications while the use of a minimally invasive approach and concurrent cystolithotomy had a decreased risk. Over the study period, the national use of simple prostatectomy decreased, on average, by 145 cases per year (P = .002). By 2012, 135/2580 procedures (5%) were performed using a minimally invasive approach. CONCLUSION: The nationwide utilization of SP for BPH has decreased. Bleeding complications are common, but perioperative mortality is low. Patients who are older, black race, or have multiple comorbidities are at higher risk of complications. Minimally invasive approaches, which are becoming increasingly utilized, may reduce perioperative morbidity. PMID- 26276575 TI - Instrument Life for Robot-assisted Laparoscopic Radical Prostatectomy and Partial Nephrectomy: Are Ten Lives for Most Instruments Justified? AB - OBJECTIVE: To investigate the rate of premature instrument exchange during robot assisted laparoscopic radical prostatectomy (RALRP) and robot-assisted partial nephrectomy (RAPN). The majority of robotic instruments have a predetermined lifespan of 10 uses; however, it is unknown if instruments are routinely exchanged before 10 uses in clinical practice. METHODS: We retrospectively reviewed instrument use in consecutive RALRP and RAPN cases performed by high volume robotic surgeons at 1 tertiary care center between January 2011 and October 2014. The number of instruments used per case was evaluated and instances of additional instrument utilization were noted. Exchange number was compared between the first and second half of cases performed. Operative times were compared between cases with and without exchange. Student's t-test and Pearson's chi(2)-test were used to determine statistical significance. RESULTS: Three surgeons performed 1579 RALRP procedures and 2 surgeons performed 313 RAPN procedures. During RALRP, monopolar curved scissors required exchange in 12.4% cases. Other instruments were exchanged in less than 2% of cases. Exchange rates were similar to those for RAPN. Only exchange of Prograsp forceps decreased with increasing surgeon experience (P = .02) and instrument exchange did not lengthen operative times (P >.05 for all instruments). CONCLUSION: During RALRP and RAPN, monopolar curved scissors required exchange in approximately 10% of cases whereas other instruments were rarely exchanged. Robotic instrument lifetime may not uniformly be 10 uses. The preset lifetime of robotic instruments and/or pricing should be reevaluated. PMID- 26276576 TI - Thymosin beta4 induces proliferation, invasion, and epithelial-to-mesenchymal transition of oral squamous cell carcinoma. AB - The epithelial-to-mesenchymal transition (EMT) plays a vital role in carcinogenesis, invasion, and metastasis of many epithelial tumors including oral squamous cell carcinoma (OSCC), a common malignancy of the head and neck. However, the functional role of the actin-sequestering protein thymosin beta4 (Tbeta4) in the EMT in OSCCs remains unclear. Thus, we investigated whether overexpression of Tbeta4 could induce in vitro tumorigenesis such as cell proliferation and anchorage independency and an EMT-like phenotype in OSCCs. Also, we examined whether it affects invasiveness and cell motility-associated signaling molecules. Tbeta4-overexpressing OSCCs, SCC-15_Tbeta4 and SCC 25_Tbeta4, enhanced cell proliferation and colony formation. In addition, we observed that Tbeta4 overexpression induced an EMT-like phenotype, accompanied by a decrease in expression of the epithelial cell marker E-cadherin and an increase in expression of mesenchymal cell markers vimentin and N-cadherin. Also, the expression level of Twist1, an EMT-inducing transcription factor, was significantly enhanced in SCC-15_Tbeta4 and SCC-25_Tbeta4 cells. Tbeta4 overexpression augmented in vitro invasion and MMP-2 activity and enhanced the phosphorylation of paxillin and cortactin and expression of LIMK1. Taken together, these results suggest that Tbeta4 overexpression could be one of the causes of tumorigenesis and progression in OSCCs. Further investigation on the Tbeta4 molecule would encourage the development of specific targets for cancer treatment. PMID- 26276577 TI - Austromegabalanus psittacus barnacle shell structure and proteoglycan localization and functionality. AB - Comparative analyzes of biomineralization models have being crucial for the understanding of the functional properties of biominerals and the elucidation of the processes through which biomacromolecules control the synthesis and structural organization of inorganic mineral-based biomaterials. Among calcium carbonate-containing bioceramics, egg, mollusk and echinoderm shells, and crustacean carapaces, have being fairly well characterized. However, Thoraceca barnacles, although being crustacea, showing molting cycle, build a quite stable and heavily mineralized shell that completely surround the animal, which is for life firmly cemented to the substratum. This makes barnacles an interesting model for studying processes of biomineralization. Here we studied the main microstructural and ultrastructural features of Austromegabalanus psittacus barnacle shell, characterize the occurrence of specific proteoglycans (keratan-, dermatan- and chondroitin-6-sulfate proteoglycans) in different soluble and insoluble organic fractions extracted from the shell, and tested them for their ability to crystallize calcium carbonate in vitro. Our results indicate that, in the barnacle model, proteoglycans are good candidates for the modification of the calcite crystal morphology, although the cooperative effect of some additional proteins in the shell could not be excluded. PMID- 26276578 TI - Trophic ecology, behaviour and host population dynamics in Echinococcus multilocularis transmission. AB - The life cycle of the cestode Echinococcus multilocularis primarily involves canids and small mammals (rodents, lagomorphs) as definitive and intermediate hosts, respectively. Several surveys have identified marked temporal and geographical variations at different scales in the parasite's prevalence in both types of hosts, suggesting variations in the biological and ecological factors that control transmission processes. The parasite transmission from intermediate to definitive hosts is determined by the predator-prey relationship, which theoretically depends on prey population dynamics and the complex dietary response of predators to varying densities of prey species and other food items. Parasite eggs are transmitted to intermediate hosts via carnivore faeces, whose distribution in the environment is driven by the defecating behaviour of final hosts. We reviewed field-based studies that address issues related to the trophic ecology and behaviour of definitive hosts, interactions between definitive and intermediate hosts, and E. multilocularis transmission both in wild and domestic animals in rural and urban environments. Two density-dependent mechanisms control the transmission dynamics in definitive hosts: one is based on the variations in the availability of intermediate hosts, and the other is based on the variations in the density of the definitive host and its faeces. Non-linearity and the direct and delayed responses of definitive host contamination in relation to intermediate host population variations were recorded. The dietary response of the red fox was shown to be complex when abundant alternative resources were available (anthropogenic food, multiple intermediate host prey species). Micro local hotspots of parasite transmission to intermediate hosts in a landscape, as well as areas of higher risk for human contamination in village and urban settings, may be explained by the definitive hosts' activity patterns and defecation behaviour. PMID- 26276579 TI - Evaluation of an ELISA using recombinant Sslambda20DeltaB3 antigen for the serological diagnosis of Sarcoptes scabiei infestation in domestic and wild rabbits. AB - An ELISA, based on the Sarcoptes scabiei Sslambda20DeltaB3 inmunodominant antigen, was evaluated for the detection of antibodies to S. scabiei in experimentally infested (n=10), farm (n=109), and wild (n=78) rabbit sera. The S. scabiei antigen Sslambda20DeltaB3, a major structural protein present over the entire mite's body, was produced as a recombinant protein in Escherichia coli and purified for its use in the ELISA. The resulting ELISA showed, in experimentally infested domestic rabbits, detectable specific antibody responses (IgG) above the cut off level from week three post-infestation indicating that the assay is able to detect positive rabbits very early during the course of the infestation. The ELISA was validated on a panel of 109 domestic breeding rabbit sera collected from 26 Spanish farms, of which 41 were obtained from rabbits with skin lesions compatible with sarcoptic mange, 26 with skin lesions compatible with psoroptic mange, and 42 from unexposed individuals from mange-free farms. The ELISA in this group was characterized by 95% sensitivity, 97% specificity, and a high degree of repeatability. In the psoroptic mange compatible lesions group, included in the study as control group for cross-reactivity with the closely related mite Psoroptes cuniculi, cross-reacting antibodies to Sslambda20DeltaB3 S. scabiei antigen were detected in 42.30% of the rabbit sera. However, mean% OD values of the sarcoptic-mange group (55.61 +/- 39.20%) were significantly higher (p<0.001) than OD values of the psoroptic-mange (3.64% +/- 5.4%) and also of the free-mange (0.21% +/- 0.67%) groups. In addition, the ELISA was also evaluated in serum samples obtained from both naturally infested and non-infested wild rabbits from Mallorca Island. The sensitivity of the assay for this group was 100% (4 out of the 4 rabbits with sarcoptic mange compatible lesions and presence of S. scabiei mites were seropositive) and the specificity was 90% (67 out of 74 wild rabbits without detectable mange lesions were seronegative). Although, the total number of tested samples from experimentally infested, farm and wild rabbits was limited, our study showed that the ELISA is able to differentiate between infested and non-infested animals in all tested groups with very high sensitivity and specificity indicating that recombinant Sslambda20DeltaB3 is a reliable diagnostic antigen. This assay might be a cost-effective tool for detecting the presence of mangy animals and therefore helping prevent spread of mange among domestic rabbits, reducing potential transmission from female breeding rabbits to other farms, and detecting infestation with sarcoptic mange in the wild. PMID- 26276580 TI - Patterns of faecal nematode egg shedding after treatment of sheep with a long acting formulation of moxidectin. AB - Much of the current information on the effects of long-acting anthelmintics on nematode populations derives either from research farms or mathematical models. A survey was performed with the aim of establishing how moxidectin is currently being used on sheep farms in the south-east of Scotland. A study was undertaken on a subsection of the surveyed farms to examine the effects of long-acting moxidectin treatments in both spring and autumn on faecal nematode egg output. The survey showed that whole flock treatments of injectable 2% moxidectin were used to control sheep scab on 21% of farms. Injectable 2% moxidectin and oral moxidectin were used to control the periparturient rise in faecal nematode egg shedding by ewes on 13% and 55% of farms respectively. The effects of injectable 2% moxidectin treatment on faecal nematode egg shedding post-treatment in both the autumn and spring were investigated by faecal nematode egg counts at the time of treatment and at 2-weekly interval thereafter on eight and six farms in the autumn and spring, respectively. Faecal egg shedding recommenced at 8 weeks (autumn) and 4 weeks (spring) post-treatment. Counts increased to a peak and then declined. The mean (95% confidence interval) peak counts post-treatment were 2.8 (0.6, 5.1), 3.6 (1.7, 5.5) and 53.5 (25.1, 82.0) eggs per gram (EPG) for autumn treated ewes, autumn-treated lambs and spring-treated ewes respectively. The spring treated sheep showed a statistically significantly earlier return to faecal egg shedding (p=0.0125, p=0.0342) compared to both other groups, statistically significantly higher peak in egg counts than the autumn treated sheep (p<0.001) and a statistically significantly longer period of positive egg counts (p=0.0148). There was no statistically significant difference in the timing of the peak FECs between autumn and spring (p=0.211). The FECs of all groups of sheep treated with an injectable long-acting formulation of moxidectin became positive earlier than would be expected from the period of persistence given on the datasheet, but post-treatment FECs were very low compared to pre treatment counts. PMID- 26276581 TI - A New Rapid In Vitro Assay for Assessing Reactivity of Acyl Glucuronides. AB - Idiosyncratic drug toxicity is a major challenge for the pharmaceutical industry since complex and multifactorial steps are involved, the dose-dependency is unclear, and its occurrence is not reliably predictable. Whereas the exact mechanisms leading to idiosyncratic toxicity remain elusive in many cases, there are often hints at the involvement of reactive metabolites, such as acyl glucuronides formed by conjugation of carboxylic acids with glucuronic acid. Because the patient-related susceptibilities leading to idiosyncratic toxicity are not sufficiently understood, the best option for the pharmaceutical industry is to minimize drug-related risk factors such as potential acyl glucuronide formation. Here, we describe a rapid in vitro assay for the assessment of the reactivity of acyl glucuronides, on the basis of acyl glucuronide migration, that can support the selection of low-risk drug candidates in the drug discovery phase. Twenty marketed compounds with a wide range of half-lives were tested, their acyl glucuronide migration rates were determined and compared with the half lives of the respective acyl glucuronides. Ranking of acyl glucuronide stability using this method compared well with the results from existing methodologies. With this method, migration rates >20% would indicate higher risk of reactivity. This simpler approach using the acyl glucuronide migration rate is not dependent on authentic standards, therefore eliminating the requirement for either lengthy chemical synthesis or in vitro biosynthesis and purification of the 1-O-beta glucuronide. This methodology provides a rapid in vitro assay to assess acyl glucuronide stability and reactivity that is well suited for use early in the drug discovery phase. PMID- 26276583 TI - Water Encapsulation Control in Individual Single-Walled Carbon Nanotubes by Laser Irradiation. AB - Owing to one-dimensionality, nanoscale curvature, and high chemical stability, single-walled carbon nanotubes (SWNTs) have unique surfaces for gas molecules: outer surface as adsorption (exohedral) site and inner surface that provides encapsulation (endohedral) space. Because as-grown SWNTs have different structure (chirality and diameter) and they are normally bundled, it is extremely difficult to investigate the intrinsic properties of SWNTs as adsorbent. Here we demonstrate controlling adsorption and encapsulation states of water in individual suspended SWNTs using laser irradiation with monitoring of their behavior by photoluminescence measurement and perform molecular dynamics simulation. The laser heating and the pressure control make water molecules encapsulated or ejected for SWNTs, which are individually oxidized and opened with laser heating. The precise control of oxidization makes it possible to observe the cluster formation of water molecules during the encapsulation process and to confine water molecules inside SWNTs even in vacuum. PMID- 26276584 TI - Self-Organized Traveling Chemo-Hydrodynamic Fingers Triggered by a Chemical Oscillator. AB - Pulsatile chemo-hydrodynamic patterns due to a coupling between an oscillating chemical reaction and buoyancy-driven hydrodynamic flows can develop when two solutions of separate reactants of the Belousov-Zhabotinsky reaction are put in contact in the gravity field and conditions for chemical oscillations are met in the contact zone. In regular oscillatory conditions, localized periodic changes in the concentration of intermediate species induce pulsatile density gradients, which, in turn, generate traveling convective fingers breaking the transverse symmetry. These patterns are the self-organized result of a genuine coupling between chemical and hydrodynamic modes. PMID- 26276582 TI - Fasiglifam (TAK-875) Inhibits Hepatobiliary Transporters: A Possible Factor Contributing to Fasiglifam-Induced Liver Injury. AB - Fasiglifam (TAK-875), a selective G-protein-coupled receptor 40 agonist, was developed for the treatment of type 2 diabetes mellitus; however, its development was terminated in phase III clinical trials because of liver safety concerns. Our preliminary study indicated that intravenous administration of 100 mg/kg of TAK 875 increased the serum total bile acid concentration by 3 to 4 times and total bilirubin levels by 1.5 to 2.6 times in rats. In the present study, we examined the inhibitory effects of TAK-875 on hepatobiliary transporters to explore the mechanisms underlying its hepatotoxicity. TAK-875 decreased the biliary excretion index and the in vitro biliary clearance of d8-taurocholic acid in sandwich cultured rat hepatocytes, suggesting that TAK-875 impaired biliary excretion of bile acids, possibly by inhibiting bile salt export pump (Bsep). TAK-875 inhibited the efflux transporter multidrug resistance-associated protein 2 (Mrp2) in rat hepatocytes using 5 (and 6)-carboxy-2',7'-dichlorofluorescein as a substrate. Inhibition of MRP2 was further confirmed by reduced transport of vinblastine in Madin-Darby canine kidney cells overexpressing MRP2 with IC50 values of 2.41 MUM. TAK-875 also inhibited the major bile acid uptake transporter Na(+)/taurocholate cotransporting polypeptide (Ntcp), which transports d8 taurocholic acid into rat hepatocytes, with an IC50 value of 10.9 MUM. TAK-875 significantly inhibited atorvastatin uptake in organic anion transporter protein (OATP) 1B1 and OATP1B3 cells with IC50 values of 2.28 and 3.98 MUM, respectively. These results indicate that TAK-875 inhibited the efflux transporter MRP2/Mrp2 and uptake transporters Ntcp and OATP/Oatp, which may affect bile acid and bilirubin homeostasis, resulting in hyperbilirubinemia and cholestatic hepatotoxicity. PMID- 26276585 TI - In Situ and Real-Time SFG Measurements Revealing Organization and Transport of Cholesterol Analogue 6-Ketocholestanol in a Cell Membrane. AB - Cholesterol organization and transport within a cell membrane are essential for human health and many cellular functions yet remain elusive so far. Using cholesterol analogue 6-ketocholestanol (6-KC) as a model, we have successfully exploited sum frequency generation vibrational spectroscopy (SFG-VS) to track the organization and transport of cholesterol in a membrane by combining achiral sensitive ssp (ppp) and chiral-sensitive psp polarization measurements. It is found that 6-KC molecules are aligned at the outer leaflet of the DMPC lipid bilayer with a tilt angle of about 10 degrees . 6-KC organizes itself by forming an alpha-beta structure at low 6-KC concentration and most likely a beta-beta structure at high 6-KC concentration. Among all proposed models, our results favor the so-called umbrella model with formation of a 6-KC cluster. Moreover, we have found that the long anticipated flip-flop motion of 6-KC in the membrane takes time to occur, at least much longer than previously thought. All of these interesting findings indicate that it is critical to explore in situ, real-time, and label-free methodologies to obtain a precise molecular description of cholesterol's behavior in membranes. This study represents the first application of SFG to reveal the cholesterol-lipid interaction mechanism at the molecular level. PMID- 26276586 TI - Surface Tension of Supercooled Water: No Inflection Point down to -25 degrees C. AB - A dramatic increase in the surface tension of water with decreasing temperature in the supercooled liquid region has appeared as one of the many anomalies of water. This claimed anomaly characterized by the second inflection point at about +1.5 degrees C was observed in older surface tension data and was partially supported by some molecular simulations and theoretical considerations. In this study, two independent sets of experimental data for the surface tension of water in the temperature range between +33 and -25 degrees C are reported. The two data sets are mutually consistent, and they lie on a line smoothly extrapolating from the stable region. No second inflection point and no other anomalies in the course of the surface tension were observed. The new data lies very close to the extrapolated IAPWS correlation for the surface tension of ordinary water, which hence can be recommended for use, e.g., in atmospheric modeling. PMID- 26276587 TI - Chloride Inclusion and Hole Transport Material Doping to Improve Methyl Ammonium Lead Bromide Perovskite-Based High Open-Circuit Voltage Solar Cells. AB - Low-cost solar cells with high VOC, relatively small (EG - qVOC), and high qVOC/EG ratio, where EG is the absorber band gap, are long sought after, especially for use in tandem cells or other systems with spectral splitting. We report a significant improvement in CH3NH3PbBr3-based cells, using CH3NH3PbBr3 xClx, with EG = 2.3 eV, as the absorber in a mesoporous p-i-n device configuration. By p-doping an organic hole transport material with a deep HOMO level and wide band gap to reduce recombination, the cell's VOC increased to 1.5 V, a 0.2 V increase from our earlier results with the pristine Br analogue with an identical band gap. At the same time, in the most efficient devices, the current density increased from ~1 to ~4 mA/cm(2). PMID- 26276588 TI - Reversibility of Pt-Skin and Pt-Skeleton Nanostructures in Acidic Media. AB - Following a well-defined series of acid and heat treatments on a benchmark Pt3Co/C sample, three different nanostructures of interest for the electrocatalysis of the oxygen reduction reaction were tailored. These nanostructures could be sorted into the "Pt-skin" structure, made of one pure Pt overlayer, and the "Pt-skeleton" structure, made of 2-3 Pt overlayers surrounding the Pt-Co alloy core. Using a unique combination of high-resolution aberration corrected STEM-EELS, XRD, EXAFS, and XANES measurements, we provide atomically resolved pictures of these different nanostructures, including measurement of the Pt-shell thickness forming in acidic media and the resulting changes of the bulk and core chemical composition. It is shown that the Pt-skin is reverted toward the Pt-skeleton upon contact with acid electrolyte. This change in structure causes strong variations of the chemical composition. PMID- 26276589 TI - Can Metal-Organic Framework Separate 1-Butene from Butene Isomers? AB - The separation of 1-butene from the other isomers is an industrially important but challenging task because these isomers mainly differ only by the position of C?C double bond with many of their physical properties very similar. In this work, we propose using first-principles calculations that Fe-MOF-74 can be a promising candidate for the separation of 1-butene from all other isomers with high selectivity. We demonstrate that the underlying mechanism of this olefin separation is the steric interactions; that is, 1-butene with terminal double bond has the smallest steric interactions with the framework and therefore can approach the metal binding sites more closely for stronger pi-complexation. This combined effect (pi-complexation modulated by steric interactions) in MOFs with open metal sites can offer a promising design strategy for difficult separation of even longer olefin isomers by properly engineering the lengths and functional groups of the MOF linkers. PMID- 26276590 TI - Cerium-Doped Zirconium Dioxide, a Visible-Light-Sensitive Photoactive Material of Third Generation. AB - The dispersion of small amounts of Ce(4+) ions in the bulk of ZrO2 leads to a photoactive material sensitive to visible light. This is shown by monitoring with EPR the formation and the reactivity of photogenerated (lambda > 420 nm) charge carriers. The effect, as confirmed by DFT calculations, is due to the presence in the solid of empty 4f Ce states at the mid gap, which act as intermediate levels in a double excitation mechanism. This solid can be considered an example of a third-generation photoactive material. PMID- 26276591 TI - Reaction Pathway for Oxygen Reduction on FeN4 Embedded Graphene. AB - The detailed reaction pathways for oxygen reduction on FeN4 embedded graphene have been investigated using density functional theory transition-state calculations. Our first-principles calculation results show that all of the possible ORR elementary reactions could take place within a small region around the embedded FeN4 complex. It is predicted that the kinetically most favorable reaction pathway for ORR on the FeN4 embedded graphene would be a four-electron OOH dissociation pathway, in which the rate-determining step is found to be the OOH dissociation reaction with an activation energy of 0.56 eV. Consequently, our theoretical study suggests that nonprecious FeN4 embedded graphene could possess catalytic activity for ORR comparable to that of precious Pt catalysts. PMID- 26276592 TI - IR, NIR, and UV Absorption Spectroscopy of C60(2+) and C60(3+) in Neon Matrixes. AB - C60(2+) and C60(3+) were produced by electron-impact ionization of sublimed C60 and charge-state-selectively codeposited onto a gold mirror substrate held at 5 K together with neon matrix gas containing a few percent of the electron scavengers CO2 or CCl4. This procedure limits charge-changing of the incident fullerene projectiles during matrix isolation. IR, NIR, and UV-vis spectra were then measured. Ten IR absorptions of C60(2+) were identified. C60(3+) was observed to absorb in the NIR region close to the known vibronic bands of C60(+). UV spectra of C60, C60(+), and C60(2+) were almost indistinguishable, consistent with a plasmon-like nature of their UV absorptions. The measurements were supported by DFT and TDDFT calculations, revealing that C60(2+) has a singlet D5d ground state whereas C60(3+) forms a doublet of Ci symmetry. The new results may be of interest regarding the presence of C60(2+) and C60(3+) in space. PMID- 26276593 TI - X-ray Crystal Structure and Theoretical Analysis of Au25-xAgx(SCH2CH2Ph)18(-) Alloy. AB - The atomic arrangement of Au and Ag atoms in Au25-xAgx(SR)18 was determined by X ray crystallography. Ag atoms were selectively incorporated in the 12 vertices of the icosahedral core. The central atom and the metal atoms in the six [-SR-Au-SR Au-SR-] units were exclusively gold, with 100% Au occupancy. The composition of the crystals determined by X-ray crystallography was Au18.3Ag6.7(SCH2CH2Ph)18. This composition is in reasonable agreement with the composition Au18.8Ag6.2(SCH2CH2Ph)18 measured by electrospray mass spectrometry. The structure can be described in terms of shells as Au1@Au5.3Ag6.7@6*[-SR-Au-SR-Au SR-]. Density functional theory calculations show that the electronic structure and optical absorption spectra are sensitive to the silver atom arrangement within the nanocluster. PMID- 26276594 TI - Atomic Scale Identification of Coexisting Graphene Structures on Ni(111). AB - Through a combined scanning tunneling microscopy (STM) and density functional theory (DFT) approach, we provide a full characterization of the different chemisorbed configurations of epitaxial graphene coexisting on the Ni(111) single crystal surface. Top-fcc, top-hcp, and top-bridge are found to be stable structures with comparable adsorption energy. By comparison of experiments and simulations, we solve an existing debate, unambiguously distinguishing these configurations in high-resolution STM images and characterizing the transitions between adjacent domains. Such transitions, described in detail through atomistic models, occur not only via sharp domain boundaries, with extended defects, but predominantly via smooth in-plane distortions of the carbon network, without disruption of the hexagonal rings, which are expected not to significantly affect electron transport. PMID- 26276595 TI - CCl Radicals As a Carbon Source for Diamond Thin Film Deposition. AB - We use first-principles quantum mechanical calculations to study diamond thin film growth on the (100) surface using CCl radicals as the carbon source. Our results show that CCl inserts into the surface dimer C-C bonds with a barrier of 10.5 kcal/mol, roughly half of the energy required for traditional CH2 insertion (22.0 kcal/mol). In addition to this, CCl has improved surface mobility (~30.0 kcal/mol barrier, versus 35 kcal/mol for CH2, along the C-C dimer chain direction), and hydrogen abstraction from the surface is also favored via atomic Cl in the vapor phase. These results explain the lower substrate temperatures achieved in crystal diamond growth from the use of chlorinated sources in CVD processes, as opposed to the more traditional CH4/H2 derived species. Our results also suggest that further reductions in substrate temperatures are possible from using CCl as the only carbon source. PMID- 26276596 TI - Stability of NNO and NPO Nanotube Crystals. AB - We combine the USPEX evolution searching method with density functional theory using dispersion corrections (DFT-ulg) to predict the crystal structure of the NNO extended solid at high pressures (from 100 to 500 GPa). We find that the NNO nanotube (with diameter ~ 2.5 A) is the most stable form above 180 GPa. We report here the stability, electronic properties, and mechanical properties of this novel nanotube and show that it is stable above 20 GPa. To find a similar structure that might be stable at ambient conditions, we considered the NPO tube and show that it is stable at zero pressure. The NPO phase leads to an insulator to metal transition at 25 GPa, where the PP van der Waals distance approaches the covalent bond distance. The energy content of this NPO nanotube crystal is 10.6 kJ/g, which is 152% higher than that of TNT and 86% higher than that of the HMX energetic material. This is the first example of a structural energetic material, which could have important applications in igniters, incendiaries, screening smoke ammunition, and similar devices. This process illustrates how materials discovery in extreme conditions can be used to discover and stabilize novel structures. PMID- 26276597 TI - Solid-State Mesostructured Perovskite CH3NH3PbI3 Solar Cells: Charge Transport, Recombination, and Diffusion Length. AB - We report on the effect of TiO2 film thickness on charge transport and recombination in solid-state mesostructured perovskite CH3NH3PbI3 (via one-step coating) solar cells using spiro-MeOTAD as the hole conductor. Intensity modulated photocurrent/photovoltage spectroscopies show that the transport and recombination properties of solid-state mesostructured perovskite solar cells are similar to those of solid-state dye-sensitized solar cells. Charge transport in perovskite cells is dominated by electron conduction within the mesoporous TiO2 network rather than from the perovskite layer. Although no significant film thickness dependence is found for transport and recombination, the efficiency of perovskite cells increases with TiO2 film thickness from 240 nm to about 650-850 nm owing primarily to the enhanced light harvesting. Further increasing film thickness reduces cell efficiency associated with decreased fill factor or photocurrent density. The electron diffusion length in mesostructured perovskite cells is longer than 1 MUm for over four orders of magnitude of light intensity. PMID- 26276598 TI - ACS on Campus in India - 2013. PMID- 26276599 TI - Spin-Crossover Anticooperativity Induced by Weak Intermolecular Interactions. AB - As a rule, rational design of cooperative spin-crossover (SCO) molecular switches is largely based on consideration of sizes and structures of individual building blocks, whereas a meticulous analysis of crystal packing, including the weakest intermolecular interactions, is often assumed to play a secondary role or is even fully neglected. By investigating cobalt(II) clathrochelates, which do not change the molecular volume upon SCO, we showed that even weak (1.2 kcal/mol) pi...Cl intermolecular interactions can cause a pronounced anticooperativity of SCO, being more gradual in the solid state than in solution. Our results clearly demonstrate that the "chemical pressure" concept is not as general as it is thought to be, and the successful design of molecular switches requires in-depth analysis of intermolecular interactions, however weak they seem. PMID- 26276600 TI - Adapting Ruthenium Sensitizers to Cobalt Electrolyte Systems. AB - In this work, we report the use of bulky substitutions in a new heteroleptic ruthenium(II) bipyridine complex, Ru(NCS)2LL', coded TT-230 to obtain high open circuit potential in a dye-sensitized solar cell (where L is a bipyridine ligand appended with two cyclopenta(2,1-b;3,4-bA)dithiophene moieties, and L' = 4,4,' dicarboxylic acid 2,2'-bipyridine). The electrolytes based on cobalt complexes have shown significant advantages in terms of attainable open-circuit potential compared to the standard iodide/tri-iodide redox mediators. These merits of the cobalt complexes were previously realized with a porphyrin sensitizer, achieving a VOC greater than 1 V in DSC. However, with conventional Ru(II)-polypyridyl complexes such as the C101 dye, similar increase in the VOC could not be attained due to the enhanced recombination. In this work, we have shown that the use of bulky substituents can prevent the back reaction of photogenerated electron and subsequently increase the open-circuit potential of the device. The recombination processes were investigated by transient photovoltage decay measurements. PMID- 26276601 TI - Structural Dynamics of Hydrated Phospholipid Surfaces Probed by Ultrafast 2D Spectroscopy of Phosphate Vibrations. AB - The properties of biomembranes depend in a decisive way on interactions of phospholipids with hydrating water molecules. To map structural dynamics of a phospholipid-water interface on the length and time scale of molecular motions, we introduce the phospholipid symmetric and asymmetric phosphate stretch vibrations as probes of interfacial hydrogen bonds and electrostatic interactions. The first two-dimensional infrared spectra of such modes and a line shape analysis by density matrix theory reveal two distinct structural dynamics components; the first 300 fs contribution is related to spatial fluctuations of charged phospholipid head groups with additional water contributions at high hydration levels; the second accounts for water-phosphate hydrogen bonds persisting longer than 10 ps. Our results reveal a relatively rigid hydration shell around phosphate groups, a behavior relevant for numerous biomolecular systems. PMID- 26276602 TI - Freezing of Molecular Motions Probed by Cryogenic Magic Angle Spinning NMR. AB - Cryogenic magic angle spinning makes it possible to obtain the NMR spectra of solids at temperatures low enough to freeze out most molecular motions. We have applied cryogenic magic angle spinning NMR to a crystalline small-molecule solid (ibuprofen sodium salt), which displays a variety of molecular dynamics. Magic angle (13)C NMR spectra are shown for a wide range of temperatures, including in the cryogenic regime down to 20 K. The hydrophobic and hydrophilic regions of the molecular structure display different behavior in the cryogenic regime, with the hydrophilic region remaining well-structured, while the hydrophobic region exhibits a broad frozen conformational distribution. PMID- 26276603 TI - Amyloid Aggregation: Role of Biological Membranes and the Aggregate-Membrane System. AB - Several human degenerative diseases involve amyloidogenic peptides/proteins with high conformational plasticity and propensity to self-aggregate into polymeric fibrillar assemblies sharing the cross-beta structure and endowed with cytotoxic potential. Although the mechanisms of amyloid growth and toxicity are not fully understood, a common property of amyloids is their ability to interact with lipid bilayers disturbing membrane integrity. Lipid bilayers can also act as conformational catalysts, favoring protein misfolding and inducing the growth of aggregation nuclei, early oligomers, and mature fibrils with specific biophysical, structural, and toxicity features. This Perspective will highlight these effects in the context of a membrane-oligomer system where the conformational/biophysical features of either component affect those of the other. In this context, we will highlight the modulation of the protein-cell surface interaction by the content of membrane cholesterol and gangliosides, notably GM1. In particular, we will discuss data that indicate how these interactions affect the structural and stability properties of both protein and bilayers as well as the final cytotoxic effect. Our goal is to propose shared membrane-based mechanisms that could apply to any amyloidogenic peptide/protein, providing a biochemical background for amyloid growth and toxicity. PMID- 26276604 TI - Vibrational Dynamics of Interfacial Water by Free Induction Decay Sum Frequency Generation (FID-SFG) at the Al2O3(1120)/H2O Interface. AB - The dephasing dynamics of a vibrational coherence may reveal the interactions of chemical functional groups with their environment. To investigate this process at a surface, we employ free induction decay sum frequency generation (FID-SFG) to measure the time that it takes for free OH stretch oscillators at the charged (pH ~ 13, KOH) interface of alumina/water (Al2O3/H2O) to lose their collective coherence. By employing noncollinear optical parametric amplification (NOPA) technology and nonlinear vibrational spectroscopy, we showed that the single free OH peak actually corresponds to two distinct oscillators oriented opposite to each other and measured the total dephasing time, T2, of the free OH stretch modes at the Al2O3/H2O interface with a sub-40 fs temporal resolution. Our results suggested that the free OH oscillators associated with interfacial water dephase on the time scale of 89.4 +/- 6.9 fs, whereas the homogeneous dephasing of interfacial alumina hydroxyls is an order of magnitude slower. PMID- 26276605 TI - Accurate Characterization of the Peptide Linkage in the Gas Phase: A Joint Quantum-Chemical and Rotational Spectroscopy Study of the Glycine Dipeptide Analogue. AB - Accurate structures of aminoacids in the gas phase have been obtained by joint microwave and quantum-chemical investigations. However, the structure and conformational behavior of alpha-aminoacids once incorporated into peptide chains are completely different and have not yet been characterized with the same accuracy. To fill this gap, we present here an accurate characterization of the simplest dipeptide analogue (N-acetyl-glycinamide) involving peptidic bonds. State-of-the-art quantum-chemical computations are complemented by a comprehensive study of the rotational spectrum using a combination of Fourier transform microwave spectroscopy with laser ablation. The coexistence of the C7 and C5 conformers has been proved and energetically as well as spectroscopically characterized. This joint theoretical-experimental investigation demonstrated the feasibility of obtaining accurate structures for flexible small biomolecules, thus paving the route to the elucidation of the inherent behavior of peptides. PMID- 26276606 TI - Lonsdaleite Films with Nanometer Thickness. AB - We investigate the properties of potentially the stiffest quasi-2-D films with lonsdaleite structure. Using a combination of ab initio and empirical potential approaches, we analyze the elastic properties of lonsdaleite films in both elastic and inelastic regimes and compare them with graphene and diamond films. We review possible fabrication methods of lonsdaleite films using the pure nanoscale "bottom-up" paradigm: by connecting carbon layers in multilayered graphene. We propose the realization of this method in two ways: by applying direct pressure and by using the recently proposed chemically induced phase transition. For both cases, we construct the phase diagrams depending on temperature, pressure, and film thickness. Finally, we consider the electronic properties of lonsdaleite films and establish the nonlinear dependence of the band gap on the films' thicknesses and their lower effective masses in comparison with bulk crystal. PMID- 26276607 TI - Heating Isotopically Labeled Bernal Stacked Graphene: A Raman Spectroscopy Study. AB - One of the greatest issues of nanoelectronics today is how to control the heating of the components. Graphene is a promising material in this area, and it is essential to study its thermal properties. Here, the effect of heating a bilayer structure was investigated using in situ Raman spectroscopy. In order to observe the effects on each individual layer, an isotopically labeled bilayer graphene was synthesized where the two layers were composed of different carbon isotopes. Therefore, the frequency of the phonons in the Raman spectra was shifted in relation to each other. This technique was used to investigate the influence of different stacking order. It was found that in bilayer graphene grown by chemical vapor deposition (CVD), the two layers behave very similarly for both Bernal stacking and randomly oriented structures, while for transferred samples, the layers act more independently. This highlights a significant dependence on the sample preparation procedure. PMID- 26276608 TI - Spectroscopic Observation of Fractal Packing of Oxygen in Variably Modified Glassy Tetrahedral Networks. AB - The spatial distribution of bridging and nonbridging oxygen atoms in silicate glass networks with a wide range of connectivity is studied using (17)O nuclear magnetic resonance spin-lattice relaxation spectroscopy. The results demonstrate a mass fractal spatial distribution of both oxygen species in the network at the nanometer length scale. The fractal dimension increases with increasing relative fraction of these oxygen species and reaches a maximum value of ~2.6. Such locally fractal character of the structural network is key to the understanding of the apparently anomalous transport, relaxation, and localization properties that are the hallmarks of the glassy state. PMID- 26276609 TI - Two-Photon Excited State Dynamics of Dark Valence, Rydberg, and Superexcited States in 1,3-Butadiene. AB - Two-photon absorption in systems with parity permits access to states that cannot be prepared by one-photon absorption. Here we present the first time-resolved photoelectron spectroscopy study using this technique, applied to 1,3-butadiene, in which we investigated the dynamics of its dark valence, Rydberg, and superexcited states. The dark valence state dynamics are accessed via the Rydberg manifold, excited by two photons of 400 nm. We find that the 'dark' 2(1)Ag state populated in this manner has a much longer lifetime than when accesses via the 1(1)Bu 'bright' valence state when populated by one photon of 200 nm. In addition, we compared the dynamics of the 3spi- and 3dpi-Rydberg states. These Rydberg states relax to the valence manifold on a subpicosecond time scale, with the 3spi-Rydberg state decay rate being larger due to a stronger valence-Rydberg mixing. Finally, we investigated superexcited valence states that fragment or autoionize within 200 fs, likely without involving Rydberg states. PMID- 26276610 TI - Molecular Active Sites in Heterogeneous Ir-La/C-Catalyzed Carbonylation of Methanol to Acetates. AB - We report that when Ir and La halides are deposited on carbon, exposure to CO spontaneously generates a discrete molecular heterobimetallic structure, containing an Ir-La covalent bond that acts as a highly active, selective, and stable heterogeneous catalyst for the carbonylation of methanol to produce acetic acid. This catalyst exhibits a very high productivity of ~1.5 mol acetyl/mol Ir.s with >99% selectivity to acetyl (acetic acid and methyl acetate) without detectable loss in activity or selectivity for more than 1 month of continuous operation. The enhanced activity can be mechanistically rationalized by the presence of La within the ligand sphere of the discrete molecular Ir-La heterobimetallic structure, which acts as a Lewis acid to accelerate the normally rate-limiting CO insertion in Ir-catalyzed carbonylation. Similar approaches may provide opportunities for attaining molecular (single site) behavior similar to homogeneous catalysis on heterogeneous surfaces for other industrial applications. PMID- 26276611 TI - Unraveling the Electronic Heterogeneity of Charge Traps in Conjugated Polymers by Single-Molecule Spectroscopy. AB - Charge trapping is taken for granted in modeling the characteristics of organic semiconductor devices, but very few techniques actually exist to spectroscopically pinpoint trap states. For example, trap levels are often assumed to be discrete in energy. Using the well-known keto defect in polyfluorene as a model, we demonstrate how single-molecule spectroscopy can directly track the formation of charge and exciton traps in conjugated polymers in real time, providing crucial information on the energetic distribution of trap sites relative to the polymer optical gap. Charge traps with universal spectral fingerprints scatter by almost 1 eV in depth, implying that substantial heterogeneity must be taken into account when modeling devices. PMID- 26276612 TI - Gating-Associated Clustering-Dispersion Dynamics of the KcsA Potassium Channel in a Lipid Membrane. AB - The KcsA potassium channel is a prototypical channel of bacterial origin, and the mechanism underlying the pH-dependent gating has been studied extensively. With the high-resolution atomic force microscopy (AFM), we have resolved functional open and closed gates of the KcsA channel under the membrane-embedded condition. Here we surprisingly found that the pH-dependent gating of the KcsA channels was associated with clustering-dispersion dynamics. At neutral pH, the resting, closed channels were coalesced, forming nanoclusters. At acidic pH, the open gated channels were dispersed as singly isolated channels. Time-lapse AFM revealed reversible clustering-dispersion transitions upon pH changes. At acidic equilibrium, a small fraction of the channels was nanoclustered, in which the gate was apparently closed. Thus, it is suggested that opening of the gate and the dispersion are tightly linked. The interplay between the intramolecular conformational change and the supramolecular clustering-dispersion dynamics provides insights into understanding of unprecedented functional cooperativity of channels. PMID- 26276613 TI - Mixed-Monolayer-Protected Au25 Clusters with Bulky Calix[4]arene Functionalities. AB - Although various complex, bulky ligands have been used to functionalize plasmonic gold nanoparticles, introducing them to small, atomically precise gold clusters is not trivial. Here, we demonstrate a simple one-pot procedure to synthesize fluorescent magic number Au25 clusters carrying controlled amounts of bulky calix[4]arene functionalities. These clusters are obtained from a synthesis feed containing binary mixtures of tetrathiolated calix[4]arene and 1-butanethiol. By systematic variation of the molar ratio of ligands, clusters carrying one to eight calixarene moieties were obtained. Structural characterization reveals unexpected binding of the calix[4]arenes to the Au25 cluster surface with two or four thiolates per moiety. PMID- 26276614 TI - Exciton Quenching Due to Copper Diffusion Limits the Photocatalytic Activity of CdS/Cu2S Nanorod Heterostructures. AB - The formation of donor/acceptor junctions in hybrid nanomaterials is predicted to enhance photocatalytic activity as compared to single-component semiconductor systems. Specifically, nanomaterials containing a junction of n-type cadmium sulfide (CdS) and p-type copper sulfide (Cu2S) formed via cation exchange have been proposed as potential photocatalysts for reactions such as water splitting. Herein, we study the elemental distribution of Cu within these nanostructures using analytical transmission electron microscopy techniques. The resulting effects of this elemental distribution on photocatalytic activity and charge dynamics were further studied using a model photoreduction reaction and transient absorption spectroscopy. We find that copper diffusion in the hybrid nanostructure quenches the exciton lifetime and results in low photocatalytic activity; however, this effect can be partially mitigated via selective extraction. These results provide a deeper understanding of the physical processes within these hybrid nanostructures and will lead to more rational design of photocatalyst materials. PMID- 26276615 TI - Nanodiamond as a New Hyperpolarizing Agent and Its (13)C MRS. AB - In this work, we have hyperpolarized carbonaceous nanoparticles (D ~ 10 nm), that is, "nanodiamonds", with 1.1% (13)C (natural abundance) using dynamic nuclear polarization (DNP). The polarization buildup curve showed a signal enhancement with relative intensity up to 4700 at 1.4 K and 100 mW microwave power. (13)C magnetic resonance spectra (MRS) were obtained from the sample at 7 T, and the signal decayed with a T1 of 55 +/- 3s. Notably, polarization was possible in the absence of added radical, consistent with previous results showing endogenous unpaired electrons in natural nanodiamonds. These likely contribute to the shorter T1's compared to those of highly pure diamond. Despite the relatively short T1, these observations suggest that natural nanodiamonds may be useful for in vivo applications. PMID- 26276616 TI - Charge Separation in P3HT:SWCNT Blends Studied by EPR: Spin Signature of the Photoinduced Charged State in SWCNT. AB - Single-wall carbon nanotubes (SWCNTs) could be employed in organic photovoltaic (OPV) devices as a replacement or additive for currently used fullerene derivatives, but significant research remains to explain fundamental aspects of charge generation. Electron paramagnetic resonance (EPR) spectroscopy, which is sensitive only to unpaired electrons, was applied to explore charge separation in P3HT:SWCNT blends. The EPR signal of the P3HT positive polaron increases as the concentration of SWCNT acceptors in a photoexcited P3HT:SWCNT blend is increased, demonstrating long-lived charge separation induced by electron transfer from P3HT to SWCNTs. An EPR signal from reduced SWCNTs was not identified in blends due to the free and fast-relaxing nature of unpaired SWCNT electrons as well as spectral overlap of this EPR signal with the signal from positive P3HT polarons. However, a weak EPR signal was observed in chemically reduced SWNTs, and the g values of this signal are close to those of C70-PCBM anion radical. The anisotropic line shape indicates that these unpaired electrons are not free but instead localized. PMID- 26276617 TI - Amyloid Fibrils: Formation, Polymorphism, and Inhibition. AB - Amyloid fibrils with cross-beta spine basic architectures are prevalent and stable forms of peptides and proteins. Recent research has provided significant contributions to our understanding of the mechanisms of fibril formation and to the surprising diversity and persistence of structural polymorphism in amyloid fibrils. There have also been successful demonstrations of how molecules can be engineered to inhibit unwanted amyloid formation by different mechanisms. Future research in these areas will include investigations of mechanisms for primary nucleation and the structure of oligomeric intermediates, the general role of secondary nucleation events (autocatalysis), elucidation of the mechanisms and implications of preservation of structural morphology in amyloid propagation, and research into the largely unexplored phenomenon of cross-seeding, by which amyloid fibrils of one species induce the formation of amyloid by another species. PMID- 26276618 TI - Insight into Enhanced Cycling Performance of Li-O2 Batteries Based on Binary CoSe2/CoO Nanocomposite Electrodes. AB - In this study, binary core-shell CoSe2/CoO nanocomposites are synthesized as cathodic electrodes for the Li-O2 cell, which exhibits enhanced cycle performance. From theoretical calculations, aberration-corrected scanning transmission electron microscopy observation, and gas chromatography mass spectrum verification, we propose that an enhanced cycle performance can be attributed to the improvement of the compatibility of the cathode/Li2O2 interface, which results from preferable interaction between Li2O2 intermediates and the CoO "shell" and then reduction of interfacial Li2CO3 formation on the carbon surface. Furthermore, our findings demonstrate that the CoSe2 "core" may impact the electronic structure of surface metal ions, generating a superior cycling performance than that of pristine CoO materials. These results will offer some critical insights into the mechanistic process of Li-O2 batteries. PMID- 26276619 TI - Strong Photophysical Similarities between Conjugated Polymers and J-aggregates. AB - The photophysical properties of emissive conjugated polymer (CP) chains are compared to those of linear J-aggregates. The two systems share many properties in common, including a red-shifted absorption spectrum with increasing chain/aggregate length, enhanced radiative decay rates (superradiance) relative to a single monomer/molecule, and several vibronic signatures involving the vinyl stretching mode common to many conjugated molecules. In particular, the scaling of the 0-0/0-1 photoluminescence ratio and radiative decay rate with the inverse square root of temperature in red-phase polydiacetylene is also characteristic of linear, disorder-free J-aggregates. The strong photophysical resemblance is traced to the excitonic band structure; in one-dimensional direct band gap semiconductors as well as J-aggregates, the exciton band curvature is positive at the gamma point (k = 0). PMID- 26276620 TI - Membrane-Protein Interactions Are Key to Understanding Amyloid Formation. PMID- 26276621 TI - Reversible Adsorption of Outer-Sphere Redox Molecules at Pt Electrodes. AB - Adsorption often dominates the response of nanofluidic systems due to their high surface-to-volume ratios. Here we harness this sensitivity to investigate the reversible adsorption of outer-sphere redox species at electrodes, a phenomenon that is easily overlooked in bulk measurements. We find that even though adsorption does not necessarily play a role in the electron-transfer process, such adsorption is nevertheless ubiquitous for the widely used outer-sphere species. We investigate the physical factors driving adsorption and find that this counterintuitive behavior is mediated by the anionic species in the supporting electrolyte, closely following the well-known Hofmeister series. Our results provide foundations both for theoretical studies of the underlying mechanisms and for contriving strategies to control adsorption in micro/nanoscale electrochemical transducers where surface effects are dominant. PMID- 26276622 TI - Malaria-Induced B Cell Genomic Instability. AB - Nussenzweig and colleagues evaluate genomic instability and germinal center derived lymphomagenesis in mice infected with Plasmodium to recreate some of the hallmark characteristics of Burkitt lymphoma, a form of cancer more common in parts of Africa where malaria is endemic. PMID- 26276623 TI - Neurons Rho to Get in Shape for the Day. AB - Linking structural changes in neurons to animal behavior has proven challenging. New findings by Pesakou et al. tie daily cycles of axon arbor extension and retraction, mediated by Rho activity, to circadian and seasonal patterns of behavior in the fruit fly. PMID- 26276624 TI - An AAA+ ATPase Clamshell Targets Transposition. AB - DNA transposition plays key roles in genome diversity, pathogenesis, and evolution. Yet, structural and mechanistic information on transposition targeting and regulation is limited. Arias-Palomo and Berger now define the decameric organization of the AAA+ ATPase IstB, unveiling key insights into its targeting and regulation of IstA transposase activity. PMID- 26276625 TI - A CTCF Code for 3D Genome Architecture. AB - The architectural protein CTCF plays a complex role in decoding the functional output of the genome. Guo et al. now show that the orientation of a CTCF site restricts its choice of interacting partner, thus creating a code that predicts the three-dimensional organization of the genome. We propose a DNA extrusion model to account for orientation-specific loop formation. PMID- 26276626 TI - Lighting Up Genes in Single Cells at Scale. AB - In this issue, Shachar et al. report a high-throughput imaging position mapping platform (HIPmap) enabling large-scale, high-resolution localization of 3D gene positions in single cells. Coupling loss-of-function screens with HIPmap, the authors identify DNA replication rather than mitosis as a major determinant of genome positioning. PMID- 26276627 TI - Somatic Rearrangement in B Cells: It's (Mostly) Nuclear Physics. AB - We discuss how principles of nuclear architecture drive typical gene rearrangements in B lymphocytes, whereas translocation hot spots and recurrent lesions reflect the extent of AID-mediated DNA damage and selection. PMID- 26276628 TI - The Brain on Drugs: From Reward to Addiction. AB - Advances in neuroscience identified addiction as a chronic brain disease with strong genetic, neurodevelopmental, and sociocultural components. We here discuss the circuit- and cell-level mechanisms of this condition and its co-option of pathways regulating reward, self-control, and affect. Drugs of abuse exert their initial reinforcing effects by triggering supraphysiologic surges of dopamine in the nucleus accumbens that activate the direct striatal pathway via D1 receptors and inhibit the indirect striato-cortical pathway via D2 receptors. Repeated drug administration triggers neuroplastic changes in glutamatergic inputs to the striatum and midbrain dopamine neurons, enhancing the brain's reactivity to drug cues, reducing the sensitivity to non-drug rewards, weakening self-regulation, and increasing the sensitivity to stressful stimuli and dysphoria. Drug-induced impairments are long lasting; thus, interventions designed to mitigate or even reverse them would be beneficial for the treatment of addiction. PMID- 26276629 TI - Plasmodium Infection Promotes Genomic Instability and AID-Dependent B Cell Lymphoma. AB - Chronic infection with Plasmodium falciparum was epidemiologically associated with endemic Burkitt's lymphoma, a mature B cell cancer characterized by chromosome translocation between the c-myc oncogene and Igh, over 50 years ago. Whether infection promotes B cell lymphoma, and if so by which mechanism, remains unknown. To investigate the relationship between parasitic disease and lymphomagenesis, we used Plasmodium chabaudi (Pc) to produce chronic malaria infection in mice. Pc induces prolonged expansion of germinal centers (GCs), unique compartments in which B cells undergo rapid clonal expansion and express activation-induced cytidine deaminase (AID), a DNA mutator. GC B cells elicited during Pc infection suffer widespread DNA damage, leading to chromosome translocations. Although infection does not change the overall rate, it modifies lymphomagenesis to favor mature B cell lymphomas that are AID dependent and show chromosome translocations. Thus, malaria infection favors mature B cell cancers by eliciting protracted AID expression in GC B cells. PAPERCLIP. PMID- 26276630 TI - Clinical Sequencing Uncovers Origins and Evolution of Lassa Virus. AB - The 2013-2015 West African epidemic of Ebola virus disease (EVD) reminds us of how little is known about biosafety level 4 viruses. Like Ebola virus, Lassa virus (LASV) can cause hemorrhagic fever with high case fatality rates. We generated a genomic catalog of almost 200 LASV sequences from clinical and rodent reservoir samples. We show that whereas the 2013-2015 EVD epidemic is fueled by human-to-human transmissions, LASV infections mainly result from reservoir-to human infections. We elucidated the spread of LASV across West Africa and show that this migration was accompanied by changes in LASV genome abundance, fatality rates, codon adaptation, and translational efficiency. By investigating intrahost evolution, we found that mutations accumulate in epitopes of viral surface proteins, suggesting selection for immune escape. This catalog will serve as a foundation for the development of vaccines and diagnostics. VIDEO ABSTRACT. PMID- 26276631 TI - Hybrid Periportal Hepatocytes Regenerate the Injured Liver without Giving Rise to Cancer. AB - Compensatory proliferation triggered by hepatocyte loss is required for liver regeneration and maintenance but also promotes development of hepatocellular carcinoma (HCC). Despite extensive investigation, the cells responsible for hepatocyte restoration or HCC development remain poorly characterized. We used genetic lineage tracing to identify cells responsible for hepatocyte replenishment following chronic liver injury and queried their roles in three distinct HCC models. We found that a pre-existing population of periportal hepatocytes, located in the portal triads of healthy livers and expressing low amounts of Sox9 and other bile-duct-enriched genes, undergo extensive proliferation and replenish liver mass after chronic hepatocyte-depleting injuries. Despite their high regenerative potential, these so-called hybrid hepatocytes do not give rise to HCC in chronically injured livers and thus represent a unique way to restore tissue function and avoid tumorigenesis. This specialized set of pre-existing differentiated cells may be highly suitable for cell-based therapy of chronic hepatocyte-depleting disorders. PMID- 26276632 TI - Alternative Wnt Signaling Activates YAP/TAZ. AB - The transcriptional co-activators YAP and TAZ are key regulators of organ size and tissue homeostasis, and their dysregulation contributes to human cancer. Here, we discover YAP/TAZ as bona fide downstream effectors of the alternative Wnt signaling pathway. Wnt5a/b and Wnt3a induce YAP/TAZ activation independent of canonical Wnt/beta-catenin signaling. Mechanistically, we delineate the "alternative Wnt-YAP/TAZ signaling axis" that consists of Wnt-FZD/ROR-Galpha12/13 Rho GTPases-Lats1/2 to promote YAP/TAZ activation and TEAD-mediated transcription. YAP/TAZ mediate the biological functions of alternative Wnt signaling, including gene expression, osteogenic differentiation, cell migration, and antagonism of Wnt/beta-catenin signaling. Together, our work establishes YAP/TAZ as critical mediators of alternative Wnt signaling. PMID- 26276633 TI - A Conserved Bicycle Model for Circadian Clock Control of Membrane Excitability. AB - Circadian clocks regulate membrane excitability in master pacemaker neurons to control daily rhythms of sleep and wake. Here, we find that two distinctly timed electrical drives collaborate to impose rhythmicity on Drosophila clock neurons. In the morning, a voltage-independent sodium conductance via the NA/NALCN ion channel depolarizes these neurons. This current is driven by the rhythmic expression of NCA localization factor-1, linking the molecular clock to ion channel function. In the evening, basal potassium currents peak to silence clock neurons. Remarkably, daily antiphase cycles of sodium and potassium currents also drive mouse clock neuron rhythms. Thus, we reveal an evolutionarily ancient strategy for the neural mechanisms that govern daily sleep and wake. PMID- 26276634 TI - An Atypical AAA+ ATPase Assembly Controls Efficient Transposition through DNA Remodeling and Transposase Recruitment. AB - Transposons are ubiquitous genetic elements that drive genome rearrangements, evolution, and the spread of infectious disease and drug-resistance. Many transposons, such as Mu, Tn7, and IS21, require regulatory AAA+ ATPases for function. We use X-ray crystallography and cryo-electron microscopy to show that the ATPase subunit of IS21, IstB, assembles into a clamshell-shaped decamer that sandwiches DNA between two helical pentamers of ATP-associated AAA+ domains, sharply bending the duplex into a 180 degrees U-turn. Biochemical studies corroborate key features of the structure and further show that the IS21 transposase, IstA, recognizes the IstB*DNA complex and promotes its disassembly by stimulating ATP hydrolysis. Collectively, these studies reveal a distinct manner of higher-order assembly and client engagement by a AAA+ ATPase and suggest a mechanistic model where IstB binding and subsequent DNA bending primes a selected insertion site for efficient transposition. PMID- 26276635 TI - Rli1/ABCE1 Recycles Terminating Ribosomes and Controls Translation Reinitiation in 3'UTRs In Vivo. AB - To study the function of Rli1/ABCE1 in vivo, we used ribosome profiling and biochemistry to characterize its contribution to ribosome recycling. When Rli1 levels were diminished, 80S ribosomes accumulated both at stop codons and in the adjoining 3'UTRs of most mRNAs. Frequently, these ribosomes reinitiated translation without the need for a canonical start codon, as small peptide products predicted by 3'UTR ribosome occupancy in all three reading frames were confirmed by western analysis and mass spectrometry. Eliminating the ribosome rescue factor Dom34 dramatically increased 3'UTR ribosome occupancy in Rli1 depleted cells, indicating that Dom34 clears the bulk of unrecycled ribosomes. Thus, Rli1 is crucial for ribosome recycling in vivo and controls ribosome homeostasis. 3'UTR translation occurs in wild-type cells as well, and observations of elevated 3'UTR ribosomes during stress suggest that modulating recycling and reinitiation is involved in responding to environmental changes. PMID- 26276638 TI - SnapShot: Interactions between B Cells and T Cells. AB - Dynamic interactions between B and T cells underpin the development of adaptive humoral immune responses to infections and vaccines. Recent advances in the molecular and spatiotemporal control of these interactions during primary responses have contributed greatly to elucidating the molecular pathogenesis of numerous immunodeficiency and autoimmune diseases. The next challenge is to determine how and where memory B and T cells interact during secondary responses to facilitate the rapid and robust response that characterizes anamnestic immunity. PMID- 26276637 TI - Identification of Gene Positioning Factors Using High-Throughput Imaging Mapping. AB - Genomes are arranged non-randomly in the 3D space of the cell nucleus. Here, we have developed HIPMap, a high-precision, high-throughput, automated fluorescent in situ hybridization imaging pipeline, for mapping of the spatial location of genome regions at large scale. High-throughput imaging position mapping (HIPMap) enabled an unbiased siRNA screen for factors involved in genome organization in human cells. We identify 50 cellular factors required for proper positioning of a set of functionally diverse genomic loci. Positioning factors include chromatin remodelers, histone modifiers, and nuclear envelope and pore proteins. Components of the replication and post-replication chromatin re-assembly machinery are prominently represented among positioning factors, and timely progression of cells through replication, but not mitosis, is required for correct gene positioning. Our results establish a method for the large-scale mapping of genome locations and have led to the identification of a compendium of cellular factors involved in spatial genome organization. PMID- 26276636 TI - CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function. AB - CTCF and the associated cohesin complex play a central role in insulator function and higher-order chromatin organization of mammalian genomes. Recent studies identified a correlation between the orientation of CTCF-binding sites (CBSs) and chromatin loops. To test the functional significance of this observation, we combined CRISPR/Cas9-based genomic-DNA-fragment editing with chromosome conformation-capture experiments to show that the location and relative orientations of CBSs determine the specificity of long-range chromatin looping in mammalian genomes, using protocadherin (Pcdh) and beta-globin as model genes. Inversion of CBS elements within the Pcdh enhancer reconfigures the topology of chromatin loops between the distal enhancer and target promoters and alters gene expression patterns. Thus, although enhancers can function in an orientation independent manner in reporter assays, in the native chromosome context, the orientation of at least some enhancers carrying CBSs can determine both the architecture of topological chromatin domains and enhancer/promoter specificity. These findings reveal how 3D chromosome architecture can be encoded by linear genome sequences. PMID- 26276639 TI - [Editorial]. PMID- 26276640 TI - [Treatment of lower limb varicose veins in 2015: The present and the future]. AB - The introduction of intravenous therapy (ultrasound-guided foam sclerotherapy, laser, radiofrequency) has considerably changed radical treatment of superficial venous insufficiency. The recent granting of reimbursable status for radio frequency thermal ablation has led us to propose radical synthetic treatment for varicose veins. The treatment is based on Doppler ultrasound exploration with detailed varicose cartography, taking into account the affected area (large or small saphenous vein), the site of the point or points of leakage, the diameter of the incontinent saphenous vein, whether the saphenous vein and tributaries are rectilinear or sinuous, and the depth of the varicose network in relation to the skin surface. The decision to implement radical therapy is based on the stage of the disease, particularly in the event of trophic lesions, and takes into consideration both the functional and aesthetic impairment caused by the varicose disorder. All of the foregoing factors affect the choice of treatment, which is also based upon the availability of the various technical approaches mentioned, upon full control of the benefits and limitations of each of the various methods, and upon informed patient consent with regard to the various options proposed: surgery, essentially involving stripping and phlebectomy or endovenous treatments: chemical ablation via ultrasound-guided foam sclerotherapy, and laser or radiofrequency thermal ablation. PMID- 26276641 TI - Dexamethasone versus ondansetron in the prevention of postoperative nausea and vomiting in patients undergoing laparoscopic surgery: a meta-analysis of randomized controlled trials. AB - BACKGROUND: Dexamethasone is an antiemetic alternative to ondansetron. We aimed to compare the effects of dexamethasone and ondansetron in preventing postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic surgery. METHODS: We searched PubMed, Embase, Medline and Cochrane Library (from inception to July 2014) for eligible studies. The primary outcome was the incidence of PONV during the first 24 h after surgery. The secondary outcomes included PONV in the early postoperative stage (0-6 h), PONV in the late postoperative stage (6-24 h), and the postoperative anti-emetics used at both stages. We calculated pooled risk ratios (RR) and 95 % CIs using random- and fixed-effects models. RESULTS: Seven trials involving 608 patients were included in this meta-analysis, which found that dexamethasone had a comparable effectiveness in preventing PONV (RR, 0.91; 95 % CI, 0.73-1.13; P = 0.39) with that of ondansetron within 24 h of laparoscopic surgery, with no evidence of heterogeneity among the studies (I(2) = 0 %; P = 0.71). In the early postoperative stage (0-6 h), ondansetron was better at decreasing PONV than dexamethasone (RR, 1.71; 95 % CI, 1.05-2.77; P = 0.03), while in the late postoperative stage (6-24 h), dexamethasone was more effective in preventing PONV than ondansetron (RR, 0.51; 95 % CI, 0.27-0.93; P = 0.03). There was no significant difference in the postoperative anti-emetics used (RR, 0.90; 95 % CI, 0.67-1.19; P = 0.45). CONCLUSIONS: Dexamethasone was as effective and as safe as ondansetron in preventing PONV. Dexamethasone should be encouraged as an alternative to ondansetron for preventing PONV in patients undergoing laparoscopic surgery. PMID- 26276642 TI - Parent's experiences of counselling and their need for support following a prenatal diagnosis of congenital heart disease--a qualitative study in a Swedish context. AB - BACKGROUND: Prenatal screening for foetal cardiac abnormalities has been increasingly practiced in Sweden during the last 25 years. A prenatal diagnosis may have medical benefits but may also cause sustained parental psychological distress. The aim of this study was to explore pregnant women's, and their partner's, experiences of counselling and need for support during continued pregnancy following a prenatal diagnosis of a cardiac defect. A second aim was to use this information to propose a structured follow-up programme for continued support after the first counselling. METHOD: DESIGN: Qualitative study, using interviews performed 5-9 weeks after a prenatal diagnosis of congenital heart disease. SETTING: A tertiary foetal cardiology unit in Sweden Sample: Six pregnant women and their 6 partners, consecutively recruited after a prenatal diagnosis of an isolated and significant cardiac defect. DATA ANALYSIS: Qualitative content analysis. RESULTS: The analysis resulted in three themes. 1/ Counselling and making a decision--the importance of knowledge and understanding: Short waiting time for specialist evaluation together with clear and straightforward information was essential. Parents called for written information together with a high-quality website with relevant information about congenital heart disease. 2/ Continued support during pregnancy: Continued and easy access to health care professionals, including a paediatric specialist nurse, throughout pregnancy, was important. Contact with couples with similar experiences and social media were also considered valuable sources of support. 3/ Next step--the near future: Practical and economical issues during the postnatal hospital stay and the initial period following the hospital stay were common concerns. CONCLUSIONS: The following aspects should be considered in a structured follow up program during pregnancy after a prenatal diagnosis of CHD; written information, access to a safe web-site with information of high quality in their native language, support from parents with similar experiences and continued contact with a specialist liaison nurse with experience of paediatric cardiology. PMID- 26276643 TI - Ascaridia nymphii n. sp. (Nematoda: Ascaridida) from the alimentary tract of a severely emaciated dead cockatiel Nymphicus hollandicus. AB - This report describes Ascaridia nymphii n. sp., a new species isolated from the alimentary tract of cockatiel Nymphicus hollandicus in Japan. More than 63 nematodes were found in the formalin-fixed small intestine, ventriculus, proventriculus and crop of a 48-day-old young cockatiel that died after exhibiting severe emaciation. No nematode eggs were observed in the faecal examination performed while the cockatiel was alive, but Cryptosporidium oocysts were found. The intestinal mucosa was damaged considerably. Male worms had two alate spicules, well-developed precloacal sucker and a tail with ventrolateral caudal alae and mainly 11 pairs of papillae. Nuclear partial (813 bp) 18S ribosomal RNA gene (18S rDNA) sequences obtained from two female samples were mutually identical. They respectively showed 99.1 and 98.6% identities to those from Ascaridia numidae and Ascaridia galli. Phylogenetic analysis using this locus indicated the present nematode as Ascaridia species. The mitochondrial NADH dehydrogenase subunit 2 gene (nad2) sequences obtained for four samples were mutually identical. They respectively showed 98.7, 85.7 and 82.2% identities with those from Ascaridia columbae, Ascaridia sp. and A. galli. Combining the morphological and sequencing data from two loci, the present nematode was identified as A. nymphii n. sp., which is closely related with A. columbae. This report is the first of a study examining the distribution of Ascaridia species in captive parrots in Japan. This study also identified the trachea and cloaca, like Cryptosporidium baileyi, as the possible location of Cryptosporidium avian genotype V in avian hosts. PMID- 26276644 TI - Impact of family ownerships, individual hygiene, and residential environments on the prevalence of pediculosis capitis among schoolchildren in urban and rural areas of northwest of Iran. AB - In the appraisal of head lice outbreak, in addition to socioeconomic factors and availability of health care services, environmental conditions of the households must be taken into account. However, interviewing with children or mailing questionnaires to families may not reflect the actualities. Therefore, in this study, all the inclusive factors which may be associated with head lice outbreak were thoroughly and closely investigated. The data were collected by examining students at schools and surveying patients' households. A questionnaire concerning children's personal hygienic practices, family features, and environmental conditions of the households was filled out during the close assessment of the residential area. The overall prevalence of head lice was obtained as 5.9%, and the difference was not significant within the urban (5.1%) and rural (6.1%) communities. Overall, the number of infested students was more frequent in girls (6.6%) than boys (2.8%), but the difference was not significant. The highest infestation rate was obtained in the examined students whose fathers were unemployed, farmer, and herdsman. Family income showed greater correlation with the prevalence of pediculosis capitis. A high frequency of pediculosis capitis was identified among the students who were sharing individual items with siblings. Assessment of households showed that room flooring material and keeping animals at home were highly correlated with head lice prevalence. Households should be informed that infestations happen, irrespective of socioeconomic status. However, the physical and environmental conditions of living areas and households play an important role in head lice prevention. PMID- 26276646 TI - Effects of post-sampling analysis time, type of blood samples and collection tubes on values of blood gas testing. AB - AIM: To investigate effects of post-sampling analysis time, a type of blood samples and collection tubes on blood gas testing. METHODS: This study included 100 patients at the Clinic for Pulmonary Diseases, Clinical Centre Sarajevo. The partial pressure of oxygen (pO2) and carbon dioxide (pCO2), and the oxygen saturation level of hemoglobin (sO2) were analyzed in the arterial blood samples (ABS) and capillary blood samples (CBS) by a potentiometric method using a blood gas analyzer ABL 555 (Radiometer, Copenhagen, Denmark). Paired measurements of ABS were performed within 15 minutes and after 60 minutes from sampling and compared. The results of CBS obtained within 15 minutes were compared with matching ABS results, as well as the results obtained from CBS within 15 minutes taken into glass and plastic tubes. RESULTS: pO2 and sO2 values were significantly lower after 60 minutes compared to those within 15 minutes in ABS (9.20+/-1.89 vs. 9.51+/-1.95 and 91.25+/-5.03 vs. 92.40+/-4.5; p<0.01, respectively). Values of pO2 and sO2 in CBS were significantly lower than values obtained in ABS (8.92+/-2.07 vs. 9.51+/-1.95 and 91.25+/-4.86 vs. 92.40+/-4.50; p<0.01, respectively). Obtained pO2 and sO2 values in CBS in the plastic tubes were higher than those in the glass tubes (8.50+/-1.98 vs. 7.89+/-2.0 and 89.66+/ 11.04 vs. 88.23+/-11.22, p<0.01 respectively). pCO2 blood values were not influenced significantly (p>0.05). CONCLUSION: The length of post-sampling analysis time, a type of blood samples and collection tubes have significant impact on blood oxygen parameters. Analysis within 15 minutes after blood sampling is considered as appropriate. PMID- 26276645 TI - Green synthesis of silver nanoparticles from Cassia roxburghii-a most potent power for mosquito control. AB - Mosquitoes transmit serious human diseases, causing millions of deaths every year. The use of synthetic insecticides to control vector mosquitoes has caused physiological resistance and adverse environmental effects in addition to high operational cost. Insecticides of synthesized natural products for vector control have been a priority in this area. In the present study, silver nanoparticles (AgNPs) synthesized using Cassia roxburghii plant leaf extract against Anopheles stephensi, Aedes aegypti, and Culex quinquefasciatus were determined. Larvae were exposed to varying concentrations of synthesized AgNPs (12, 24, 36, 48, and 60 MUg/mL) and aqueous leaf extracts (60, 120, 180, 240, and 300 MUg/mL) for 24 h. The synthesized AgNPs were characterized by UV-Vis spectrum, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), with energy dispersive X-ray spectroscopy analysis (EDX), transmission electron microscopy, and X-ray diffraction analysis (XRD). Compare to aqueous extracted synthesized AgNPs showed extensive mortality rate against An. stephensi, Ae. aegypti, and C. quinquefasciatus with the LC50 and LC90 values that were 26.35, 28.67, 31.27 and 48.81, 53.24, and 58.11 MUg/mL, respectively. No mortality was observed in the control. This is the first report on mosquito larvicidal activity of plant synthesized nanoparticles. Thus, the use of C. roxburghii to synthesize silver nanoparticles is a rapid, eco-friendly, and a single-step approach, and the AgNPs formed can be potential mosquito larvicidal agents. Therefore, this study proves that C. roxburghii is a potential bioresource for stable, reproducible nanoparticle synthesis (AgNPs) and also can be used as an efficient mosquito control agent. This is the first report on the larvicidal activity of the plant extract and AgNPs. PMID- 26276647 TI - Association of LPIN1 gene variations with markers of metabolic syndrome in population from Bosnia and Herzegovina. AB - AIM: To investigate association of two LPIN1 gene variations with main traits of metabolic syndrome (MS) (waist circumference, body mass index, blood pressure, triglycerides, HDL-cholesterol and fasting glucose levels) in population from Bosnia and Herzegovina. METHODS: This study included 43 patients with metabolic syndrome and 43 healthy controls from General Hospital in Tesanj, Bosnia and Herzegovina. Subjects were genotyped for two LPIN1 gene variations (rs11693809: C>T and rs2716610: C>T) by real time PCR method. RESULTS: In control subjects LPIN1 polymorphism, rs2716610: C>T, was significantly associated with a lower body mass index (BMI) (p=0.008) and waist circumference (p=0.008). The second analyzed rs11693809: C>T polymorphism was associated with lower blood HbA1c levels (p=0.048) in a group of MS patients. CONCLUSION: Results of our study suggest that rs2716610: C>T polymorphism of LPIN1 gene could have a protective effect against development of metabolic syndrome, while rs11693809: C>T might affect a glucose control in patients with MS. PMID- 26276648 TI - Alpha-lipoic acid reduces body weight and regulates triglycerides in obese patients with diabetes mellitus. AB - AIM: To determine an influence of alpha-lipoic acid to reduction of body weight and regulation of total cholesterol concentration, triglycerides and glucose serum levels in obese patients with diabetes mellitus type 2. METHODS: A prospective study includes two groups of obese patients with diabetes mellitus and signs of peripheral polyneuropathia: examined group (30 patients; 15 females and 15 males), and control group (30 patients; 12 females and 18 males). All were treated with metformin (850-1700 mg/day). Examined patients were additionally treated with alpha-lipoic acid 600 mg/day during 20 weeks. Body mass index and concentrations of total cholesterol, triglycerides and glucose in serum were compared before and after the treatment. RESULTS: The group treated with 600 mg alpha-lipoic acid lost significantly more weight, and had lower triglyceride level than the control group. There were no significant differences in total cholesterol and glucose serum levels between the groups. CONCLUSION: Alpha-lipoic acid of 600 mg/day treatment have influenced weight and triglycerides loss in obese patients with diabetes mellitus type 2. It should be considered as an important additive therapy in obese patients with diabetes mellitus type 2. PMID- 26276649 TI - Positive correlation between uric acid and C-reactive protein serum level in healthy individuals and patients with acute coronary syndromes. AB - AIM: To assess serum levels and correlation between uric acid (UA) and C-reactive protein (CRP) in acute coronary syndrome (ACS) and apparently healthy individuals. METHODS: The cross-sectional study included 116 examinees of age 44 to 83 years, distributed in two groups: 80 ACS patients including 40 with acute myocardial infarction (AMI), and 40 with unstable angina pectoris (UAP), and 36 apparently healthy (control group) individuals. Patients with ACS were hospitalized at the Cardiology Clinic, Clinical Centre Sarajevo in the period October- December 2012. Laboratory analyses were conducted by standard methods. The accepted statistical significance level was p<0.05. RESULTS: Serum levels of CRP and UA were higher in patients with ACS as compared to control group (p<0.01). The median serum UA was insignificantly lower, and CRP was significantly higher in patients with AMI compared to UAP (p=0.118 and p=0.001, respectively). CRP and UA correlated positively in both ACS and control groups (rho=0.246; p=0.028 and rho=0.374; p=0.027). A positive correlation between serum CRP and UA was noted in patients with AMI, but negative in patients with UAP (p>0.05). CONCLUSION: The correlation between CRP and UA in the patients with ACS indicates the association of oxidative stress and inflammation intensity in damaged cardiomyocytes. Correlation between UA and CRP in apparently healthy individuals indicates a possible role of UA as a marker of low-grade inflammation and its potential in risk assessment in cardiovascular diseases. PMID- 26276650 TI - Role of echocardiography in diagnosis and management of complete papillary muscle rupture caused by myocardial infarction. AB - AIM: To evaluate the usefulness of echocardiography in the diagnosis of complete rupture of papillary muscle. METHODS: Transthoracic (TTE) and transesophageal echocardiography (TEE) was performed with the ATL 3000 HDI Ultrasound Inc (Bothell, WA, USA) with a 2.5 MHz transducer and 5-7 MHz multiplane phased array transducer. We are reporting about two patients (a 45 and a 51-year old male) with complete ruptures of papillary muscle following acute myocardial infarction (AMI). RESULTS: Both patients were previously treated with fibrinolysis in their local hospitals, 400 and 300 km, respectively, away from our hospital. Massive mitral regurgitation developed in both followed by rapid deterioration of hemodynamic state and severe heart failure, because of which both were transferred by helicopter to the Coronary Care Unit of our clinic. The diagnosis of complete papillary muscle rupture was confirmed in both patients by TTE and TEE. Due to the significant deterioration in their hemodynamic state, vasoactive drugs and intra-aortic balloon pump support were applied. Both patients then underwent mitral valve replacement, accompanied by concomitant coronary artery bypass grafting in one case. CONCLUSION: Transesophageal echocardiography is a more accurate and rapid diagnostic method in patients with mechanical complications of AMI than TTE. PMID- 26276651 TI - Impact of reperfusion therapy and infarct localization on frequency of premature ventricular beats in acute myocardial infarction. AB - AIM: To determine the impact of infarct localization and types of reperfusion therapy on the frequency of ventricular premature beats (VPBs) in patients with acute myocardial infarction (AMI) and reduced left ventricular ejection fraction (LVEF). METHODS: A total of 705 patients with acute ST elevation myocardial infarction (STEMI) were divided according to the infarct localization (anteroseptal, anterolateral, inferior and posterior) and reperfusion therapy (fibrinolysis or percutaneous coronary intervention with stenting) into two groups: LVEF<45% was an experimental group and LVEF>45% was a control group. The occurrence of VPBs<10 per hour was defined as a non-significant, and the occurrence of VPBs>10 per hour defined as a significant. RESULTS: In patients with fibrinolysis therapy and LVEF<45% significant number of VPBs were in anteroseptal (p=0.017), anterolateral (p<0.001) and posterior AMI (p<0.001), but in patients with percutaneous coronary intervention (PCI) and LVEF<45% significant number of VPBs were only in anteroseptal AMI (p=0.001) localization. CONCLUSION: In patients with reduced ejection fraction in AMI, treatment with PCI method has a better antiarrhythmic effect compared to fibrinolysis treatment. PMID- 26276652 TI - Possibilities of differentiation of solitary focal liver lesions by computed tomography perfusion. AB - AIM: To evaluate possibilities of computed tomography (CT) perfusion in differentiation of solitary focal liver lesions based on their characteristic vascularization through perfusion parameters analysis. METHODS: Prospective study was conducted on 50 patients in the period 2009-2012. Patients were divided in two groups: benign and malignant lesions. The following CT perfusion parameters were analyzed: blood flow (BF), blood volume (BV), mean transit time (MTT), capillary permeability surface area product (PS), hepatic arterial fraction (HAF), and impulse residual function (IRF). During the study another perfusion parameter was analyzed: hepatic perfusion index (HPI). All patients were examined on Multidetector 64-slice CT machine (GE) with application of perfusion protocol for liver with i.v. administration of contrast agent. RESULTS: In both groups an increase of vascularization and arterial blood flow was noticed, but there was no significant statistical difference between any of 6 analyzed parameters. Hepatic perfusion index values were increased in all lesions in comparison with normal liver parenchyma. CONCLUSION: Computed tomography perfusion in our study did not allow differentiation of benign and malignant liver lesions based on analysis of functional perfusion parameters. Hepatic perfusion index should be investigated in further studies as a parameter for detection of possible presence of micro metastases in visually homogeneous liver in cases with no lesions found during standard CT protocol. PMID- 26276653 TI - Familial autoimmune thyroid disease and PTPN-22. AB - AIM: Autoimmune thyroid disease (AITD) is a multifactorial disease with a genetic predisposition. The protein tyrosine phosphatase-22 (PTPN-22) gene is a powerful inhibitor of T-cell activation. The aim of this study was to compare messenger RNA (mRNA) PTPN22 expression between healthy persons and patients with hypothyroidism and with their affected relatives. METHODS: This was a cross sectional, prospective and descriptive study. DNA was extracted from leukocytes (4,000-10,000 cells) using the Magna Pure LC 2.0 Instrument and MagNA Pure LC RNA Isolation Kit I (Roche, Germany). A real-time polymerase reaction (qPCR) was performed utilizing the primer sets specific for the PTPN-22 gene, and the succinate dehydrogenase complex, the subunit A, Flavoprotein (Fp) (SDHA) constitutive gene. All reactions were performed with the 7500 Fast Real Time PCR System (Applied Biosystems, Applera International, Inc. Cheshire, UK) employing the SYBR Advantage qPCR Premix Kit (Clontech, USA). RESULTS: Twenty five patients with AITD (hypothyroidism), all females (mean age 39.6 +/- 11.8 years) and 23 control subjects (mean age 24.4 +/- 4.2 years) were included in the study. There was no statistical difference between both groups in PTPN-22 mRNA expression (p = 0.125). CONCLUSION: There is no clear difference in mRNA PTPN-22 expression. The ideal genes for a systematic screening for familial AITD are yet to be found. PMID- 26276654 TI - Methicillin-resistant S. aureus (MRSA), extended-spectrum (ESBL)- and plasmid mediated AmpC beta-lactamase -producing Gram-negative bacteria associated with skin and soft tissue infections in hospital and community settings. AB - AIM: To investigate the characteristics of meticillin-resistant S. aureus (MRSA), extended-spectrum (ESBL), and plasmid-mediated AmpC beta-lactamase producing Gram negative bacteria causing skin and soft tissue infections (SSTIs) in hospital and outpatient settings of Zenica-Doboj Canton, Bosnia and Herzegovina. METHODS: Antibiotic susceptibility was determined by disc-diffusion and broth microdillution methods according to CLSI guidelines. MecA gene was detected by PCR, and genetic characterization of MRSA was performed using spa-typing and the algorithm based upon repeat patterns (BURP). Double-disk-synergy test was used to screen for ESBLs. PCR was used to detect blaESBL alleles. Genetic relatedness of the strains was tested by PFGE. RESULTS: Seventeen in-patients with MRSA, 13 with ESBL-producing Gram-negative bacteria and three patients co-infected with both, were detected. Five MRSA and 16 ESBL-producing Gram-negative bacteria were found in outpatient samples. Klebsiella spp. was isolated in 11 in- and seven outpatients. MLST CC152 was the most prevalent MRSA. Seven (38.9%) Klebsiella spp. yielded amplicons with primers specific for SHV, TEM-1 and CTX-M group 1 beta-lactamases. Eight K. pneumonia (44.4%) and 16 (64%) MRSA (including the in- and outpatient) strains were clonally related. CONCLUSION: The presence of MRSA and ESBL-producing organisms causing SSTIs in the community poses a substantial concern, due to the high morbidity and mortality associated with possible consequent hospital infections. PMID- 26276655 TI - Emergence of extensive drug-resistant (XDR) Acinetobacter baumanniiin the Clinical Center University of Sarajevo, Bosnia and Herzegovina. AB - AIM: Recently increased attention and interest for Acinetobacterbaumannii are the result of the occurrence of multidrug resistant (MDR), extensive drug resistant (XDR) and pandrug resistant (PDR) isolates around the world. The aim of this study was to examine the resistance of A. baumannii isolates to antimicrobials in Clinical Centre University of Sarajevo, Bosnia and Herzegovina. METHODS: Two hundred and fifty-seven A.baumannii isolates were collected between July 2011 and June 2012 in different wards and from different clinical samples. Multidrug resistant, XDR and PDR were defined according to international expert proposal for interim standard definitions for acquired resistance. RESULTS: A total of 257 A. baumannii isolates showed eleven different patterns of resistance, of which ten patterns corresponded to MDR and one corresponded to XDR (sensitive only to colistin). Multidrug resistant and XDR strains were the most common at Intensive Care Units and surgical departments. The largest numbers of isolates were found in wound swabs, blood and bronchial aspirate. CONCLUSION: This is the first report of XDR A. baumannii in the 2000-bed Clinical Centre University of Sarajevo, Bosnia-Herzegovina. Although XDR strains have been detected, the resistance to colistin has not. The elevated prevalence of these strains indicates that local antibiotic prescription policies should be revised and infection prevention and control should be improved. PMID- 26276656 TI - Brucellosis in children in Bosnia and Herzegovina in the period 2000 - 2013. AB - AIM: To analyse clinical, laboratory and epidemiological characteristics of brucellosis in children in Bosnia and Herzegovina. METHODS: The study included 246 children aged 0-18 years, who were hospitalized in Clinics and Departments for Infectious Diseases in Tuzla, Sarajevo, Banja Luka, Zenica and Bihac in the period 2000-2013, in whom the diagnosis of brucellosis was established based on anamnestic data, clinical features and positive results from blood culture and/or positive results from one of the serological tests. RESULTS: In this period, a total of 2630 patients, 246 (9.35%) of whom were children, were treated from brucellosis at the Clinics and Departments in Bosnia and Herzegovina. In the majority of cases, the children were from rural parts of the country, 226 (91.87%);214 (87.04%) cases had direct contact with sick animals, sick family member or consumption of unpasteurized dairy products from farms where brucellosis had been already established. Male children predominated, 157 (63.82%). The most frequent clinical features in affected children were fever, 194 (78.86%) and joint pain, 158 (64.22%). The average duration of antimicrobial treatment was 42.85 +/- 10.67 days. A total of 228 (92.68%) children were completely cured, while relapses occurred in 18 (7.32%) children. CONCLUSION: Since brucellosis is an endemic disease in Bosnia and Herzegovina, it is important that physicians in their daily practice consider brucellosis and establish proper diagnosis and therapy in children with prolonged fever, arthralgia, leukopenia and positive epidemiological data, especially in rural parts of the country. PMID- 26276657 TI - Differences in newborn umbilical cord care. AB - AIM: To investigate the frequency of different cord care practices as well recommendations to parents on cord care, along with the need to identify as well as reach the consensus on best cord care practices and other procedures in newborn care among health workers. METHODS: The study was conducted among 110 health care workers at the nursery departments in two general hospitals, six community-health nursing services and 16 pediatric practices in Eastern Croatia. The questionnaire created for this research has evaluated different cord care practices and recommendations to parents, a need to identify, as well as reach the consensus on best practices in cord care and other procedures in newborn care. RESULTS: Statistically significant differences have been found among respondent groups in three "dry" cord practices (p=0.000, p=0.002, and p=0.004, respectively) and three "wet" cord practices (p=0.000, p=0.001, and p=0.000, respectively). Significant differences were determined in three types of recommendations to parents about the care of "dry" cord (p=0.000, p=0.000, and p=0.002, respectively) and two recommendations for "wet" cord (p =0.000, p=0.000, respectively). The majority of respondents stressed the need for publishing guidelines on cord care, 104 (94.5%), and for other procedures in newborn care, 108 (98.2%). More than a half of respondents, 63 (57.3%), declared the need to reach a national agreement on guidelines for umbilical cord care. CONCLUSION: Healthcare workers employ, as well as recommend, different umbilical cord care practices. It is necessary to prepare and reach a national agreement on written guidelines for umbilical cord care as well as for other procedures in newborn care. PMID- 26276658 TI - Effects of perioperative statin treatment on postoperative atrial fibrillation and cardiac mortality in patients undergoing coronary artery bypass grafting: a propensity score analysis. AB - AIM: To evaluate the effect of perioperative statin treatment on postoperative atrial fibrillation and cardiac mortality in patients undergoing coronary artery bypass grafting. METHODS: A total of 1890 patients who underwent isolated coronary artery bypass were analyzed retrospectively, of which 425 patients (22.4%) older than 70 were included in the study. The demographic properties, preoperative, operative and postoperative data and other medications of these patients were recorded. Continuous preoperative and postoperative atorvastatin therapy were received by 124 (29.17%) patients; 301 (70.82%) patients were matched to a control group (no-statin group). The two groups were matched by propensity score analysis in terms of atrial fibrillation development and cardiac mortality. RESULTS: Medical history, medical treatment, cardiovascular history, and operative characteristics demonstrated significant heterogeneity in both groups. Postoperative atrial fibrillation was similar in both groups. Before propensity score matching, the percentages of patients in postoperative atrial fibrillation with respect to Atorvastain-group and No-statin-group were 13.71 and 10.3 respectively; however, those were 13.71 and 14.51 after matching. In a multivariate regression analysis, five-vessel bypass (odds ratio OR, 2.354; 95% confidence interval CI, 0.99 to 5.57) was an independent predictor of postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting. In-hospital mortality was higher in the Atorvastatin-group compared with the No-statin-group: 124 (8.9%) versus 301 (3.7%), respectively; p=0.027). CONCLUSION: Perioperative atorvastatin treatment is not found to be associated with reduced postoperative atrial fibrillation and cardiac mortality in patients undergoing isolated coronary artery bypass grafting above the age of seventy years. PMID- 26276659 TI - Efficacy of chronic statin therapy on major cardiac events after coronary artery bypass grafting: low-dose versus high-dose. AB - AIM: To investigate whether chronic statin treatment after coronary artery bypass grafting (CABG) protects patients from major cardiac events and provides percutaneous coronary intervention (PCI) free survival. METHODS: A total of 232 patients with previous CABG and chronic statin therapy were selected retrospectively and were divided into two groups according to a dosage of atorvastatin per day, e. g., 20 mg or 40 mg. Groups were compared for the major cardiac events and freedom from PCI by Kaplan Meier analysis as the primary end point. Patency of grafts including left internal thoracic artery (LITA) and saphenous vein (SVG) and progression of non-grafted native vessel disease were also evaluated as secondary end points. RESULTS: Cardiac mortality, periprocedural myocardial infarction (MI), target vessel revascularization and percutaneous coronary intervention free survival were as follows: 2.9% versus 2.1% (p=1.000); 16.1% versus 21.1% (p=0.331); 56.93% versus 52.63% (p>0.005); 58.4% versus 63.2% (log-rank test; p= 0.347) in atorvastatin 20 mg and atorvastatin 40 mg groups, respectively. However, these results were not statistically significant between two groups (p>0.005). Patency of openness of grafts including LITA and SVG and progression of non-grafted native vessel disease were similar between groups (p=0.112, p=0.779, p=0.379 and p=0.663, respectively). CONCLUSION: Low-dose long-term statin treatment had similar outcomes on major cardiac events and identical rate of freedom from percutaneous coronary intervention after coronary artery bypass grafting compared with high dose long-term statin treatment. It is better to start from low dose statin treatment after surgical interventions. PMID- 26276660 TI - Incidence of endophthalmitis after intravitreal application of anti VEGF therapy at the University Clinical Center in Tuzla, Bosnia and Herzegovina. AB - AIM: To report the incidence of endophthalmitis following the use of intravitreal injection of anti- vascular endothelial growth factor (anti VEGF) therapy. METHODS: In this retrospective study a total of 986 intravitreal bevacizumab injections were applied between January 2008 and April 2015 at the University Clinical Center Tuzla, Bosnia and Herzegovina (BiH). Since January 2012, a total of 55 intravitreal ranibizumab injections were applied and since October 2014, 60 intravitreal aflibercept injections were applied to patients. RESULTS: Two cases of endophthalmitis following intravitreal injection of bevaciuzumab occurred and none after ranibizumab or aflibercept. The overall incidence of clinical endophtahlmitis was 0.2%. CONCLUSION: The results suggest that a low rate of endophthalmitis can be achieved by means of a protocol. This is a very important study as it is the first of this kind in BiH that documents the incidence of endophthalmitis after intravitreal application. Currently, bevacizumab in BiH is most frequently used intravitreal anti-vascular endothelial growth factor due to very low price. PMID- 26276661 TI - Therapeutic efficacy and toxicity of bolus application of chemotherapy protocol in the treatment of metastatic colorectal cancer. AB - AIM: To compare efficacy and toxicity of bolus application of chemotherapy protocol, oxaliplatin, fluorouracil (bolus), leucovorin (folfox) between two groups of patients in the therapy of metastatic colorectal carcinoma (mCRC). METHODS: A total of 63 patients were treated for mCRC in the period January 2009 January 2010 at the Department of Oncology of the Cantonal Hospital Zenica, Bosnia and Herzegovina (first group, 30 patients) and at the Department of Oncology of the Clinical Hospital Centre Bezanijska kosa in Belgrade, Serbia, in the period January 2005 - January 2006 (second group, 33 patients). The patients were treated according the same protocol, i.v. bolus infusion, but in different day intervals (D), 1, 8, 15/28 days or D1-D5/28 days, respectively. In all patients the following factors were analyzed: tumor response, overall survival (OS), progression free survival, hematological and non-hematological toxicity . RESULTS: Colon was the primary localization in almost two thirds of patients. There was no statistically significant difference between the groups according to the age, hematological and non-hematological toxicity, as well as in achieved OS. Progression free survival expressed in months was in average 5 months though with a large range between minimal and maximal survival time. CONCLUSION: Both groups have shown equivalent efficacy to applied chemotherapy protocols. Overall survival in the two groups matched data from the literature. Further research should confirm success of the combination of chemotherapy protocols and their combination with the biological therapy. PMID- 26276662 TI - Differences in body mass index and height factors between men with and without varicocele. AB - AIM: Despite many studies published in recent years concerning the relationship between demographic factors and varicocele, this issue remains controversial. The aim of this study was to identify a possible influence of body mass index (BMI) and height on occurrence varicocele in men. METHODS: In a case-control study 153 patients aged 18-40 years from 2004 to 20014, with moderate and sever varicocele were studied. The BMI and height of the 153 patients with varicocele were compared with 250 men who had no varicocele as a control group. RESULTS: After the adjustment for socio-demographic factors, the risk of varicocele for obese men was lower than for overweight and normal men (OR= 0.38, 95% CI= 0.17, 0.85). The adjusted OR for varicocele in taller men was higher than in those with low height (OR= 3.42, 95% CI= 1.34, 8.72), and moderate height (OR=2.68, 95% CI= 1.12, 6.46). CONCLUSION: The results of this study indicated that tall men and non-obese men may be at higher risk of varicocele, therefore counseling and evaluation of the men at high risk of varicocele may be of benefit for reduced infertility. PMID- 26276663 TI - Genetic polymorphisms variants in interleukin-6 and interleukin-1beta patients with obstructive sleep apnea syndrome in East Northern Turkey. AB - AIM: To investigate the relationship of IL-1beta and IL-6 cytokine gene polymorphisms with obstructive sleep apnea syndrome (OSAS) in 61 patients admitted to the neurology clinic in Kafkas University Hospital with insomnia problem who were diagnosed with OSAS in sleeping labs, and 80 healthy subjects not associated with the syndrome. METHODS :Blood samples were taken to isolate DNA from patients diagnosed with OSAS based on polysomnography results and healthy controls. DNA amplification of the genes was performed with PCR. Amplification products were cut with the restriction enzymes in order to determine IL-1 gene (TaqI) and IL-6 gene (Lwel) polymorphisms. The cut DNA fragments were carried out in agarose gel electrophoresis, and RFLP analysis was performed by utilizing the images with gel imaging system. PCR products were sequenced with an Applied Biosystems Automated Sequencer. RESULTS: Polymorphic changes were observed for IL-1beta gene in 26 of 62 patients (41.9%), and 16 of the 80 (25.8%) in the control group. The incidence of polymorphic changes in IL-6 gene was in seen in seven (of the 62 patients) (11.3%), and in the 16 (20%) controls. CONCLUSION : The findings on the genomic level in OSAS may provide an important contribution to diagnosis of obstructive sleep apnea syndrome in clinical practice, as well as it helps to obtain the results easily about environmental and genetic interaction of OSAS patients. PMID- 26276664 TI - Lack of glucocorticoid-induced leucine zipper (GILZ) deregulates B-cell survival and results in B-cell lymphocytosis in mice. AB - Glucocorticoids (GC) are widely used as antiinflammatory/immunosuppressive drugs and antitumor agents in several types of lymphoma and leukemia. Therapeutic doses of GC induce growth-suppressive and cytotoxic effects on various leukocytes including B cells. Molecular mechanisms of GC action include induction of GC target genes. Glucocorticoid-induced leucine zipper (GILZ) is a rapidly, potently, and invariably GC-induced gene. It mediates a number of GC effects, such as control of cell proliferation, differentiation, and apoptosis. Here we show that deletion of GILZ in mice leads to an accumulation of B lymphocytes in the bone marrow, blood, and lymphoid tissues. Gilz knockout (KO) mice develop a progressive nonlethal B lymphocytosis, with expansion of B220(+) cells in the bone marrow and in the periphery, dependent on increased B-cell survival. Decreased B-cell apoptosis in mice lacking GILZ correlates with increased NF kappaB transcriptional activity and Bcl-2 expression. B cell-specific gilz KO mice confirmed that the effect of GILZ deletion is B-cell self-intrinsic. These results establish GILZ as an important regulator of B-cell survival and suggest that the deregulation of GILZ expression could be implicated in the pathogenesis of B-cell disorders. PMID- 26276665 TI - Erythroferrone contributes to hepcidin suppression and iron overload in a mouse model of beta-thalassemia. AB - Inherited anemias with ineffective erythropoiesis, such as beta-thalassemia, manifest inappropriately low hepcidin production and consequent excessive absorption of dietary iron, leading to iron overload. Erythroferrone (ERFE) is an erythroid regulator of hepcidin synthesis and iron homeostasis. Erfe expression was highly increased in the marrow and spleen of Hbb(Th3/+) mice (Th3/+), a mouse model of thalassemia intermedia. Ablation of Erfe in Th3/+ mice restored normal levels of circulating hepcidin at 6 weeks of age, suggesting ERFE could be a factor suppressing hepcidin production in beta-thalassemia. We examined the expression of Erfe and the consequences of its ablation in thalassemic mice from 3 to 12 weeks of age. The loss of ERFE in thalassemic mice led to full restoration of hepcidin mRNA expression at 3 and 6 weeks of age, and significant reduction in liver and spleen iron content at 6 and 12 weeks of age. Ablation of Erfe slightly ameliorated ineffective erythropoiesis, as indicated by reduced spleen index, red cell distribution width, and mean corpuscular volume, but did not improve the anemia. Thus, ERFE mediates hepcidin suppression and contributes to iron overload in a mouse model of beta-thalassemia. PMID- 26276666 TI - Convergent BCL6 and lncRNA promoters demarcate the major breakpoint region for BCL6 translocations. PMID- 26276667 TI - Targeting the leukemia cell metabolism by the CPT1a inhibition: functional preclinical effects in leukemias. AB - Cancer cells are characterized by perturbations of their metabolic processes. Recent observations demonstrated that the fatty acid oxidation (FAO) pathway may represent an alternative carbon source for anabolic processes in different tumors, therefore appearing particularly promising for therapeutic purposes. Because the carnitine palmitoyl transferase 1a (CPT1a) is a protein that catalyzes the rate-limiting step of FAO, here we investigated the in vitro antileukemic activity of the novel CPT1a inhibitor ST1326 on leukemia cell lines and primary cells obtained from patients with hematologic malignancies. By real time metabolic analysis, we documented that ST1326 inhibited FAO in leukemia cell lines associated with a dose- and time-dependent cell growth arrest, mitochondrial damage, and apoptosis induction. Data obtained on primary hematopoietic malignant cells confirmed the FAO inhibition and cytotoxic activity of ST1326, particularly on acute myeloid leukemia cells. These data suggest that leukemia treatment may be carried out by targeting metabolic processes. PMID- 26276668 TI - Autophagic vesicles on mature human reticulocytes explain phosphatidylserine positive red cells in sickle cell disease. AB - During maturation to an erythrocyte, a reticulocyte must eliminate any residual organelles and reduce its surface area and volume. Here we show this involves a novel process whereby large, intact, inside-out phosphatidylserine (PS)-exposed autophagic vesicles are extruded. Cell surface PS is a well-characterized apoptotic signal initiating phagocytosis. In peripheral blood from patients after splenectomy or in patients with sickle cell disease (SCD), the number of circulating red cells exposing PS on their surface is elevated. We show that in these patients PS is present on the cell surface of red cells in large (~1.4 um) discrete areas corresponding to autophagic vesicles. The autophagic vesicles found on reticulocytes are identical to those observed on red cells from splenectomized individuals and patients with SCD. Our data suggest the increased thrombotic risk associated with splenectomy, and patients with hemoglobinopathies is a possible consequence of increased levels of circulating mature reticulocytes expressing inside-out PS-exposed autophagic vesicles because of asplenia. PMID- 26276670 TI - IL-1beta, in contrast to TNFalpha, is pivotal in blood-induced cartilage damage and is a potential target for therapy. AB - Joint bleeding after (sports) trauma, after major joint surgery, or as seen in hemophilia in general leads to arthropathy. Joint degeneration is considered to result from the direct effects of blood components on cartilage and indirectly from synovial inflammation. Blood-provided proinflammatory cytokines trigger chondrocytes and induce the production of cartilage-degrading proteases. In the presence of erythrocyte-derived iron, cytokines stimulate radical formation in the vicinity of chondrocytes inducing apoptosis. To unravel the role of interleukin (IL) 1beta and tumor necrosis factor (TNF) alpha in the pathogenesis of this blood-induced cartilage damage, the effect of antagonizing these cytokines was examined in human in vitro cultures. Addition of recombinant human IL-1beta monoclonal antibody or IL-1 receptor antagonist resulted in a dose- and time-dependent protection of cartilage from blood-induced damage. In higher concentrations, almost complete normalization of cartilage matrix proteoglycan turnover was achieved. This was accompanied by a reduction in IL-1beta and IL-6 production in whole blood cultures, whereas TNFalpha production remained unaffected. Interestingly, addition of a TNFalpha monoclonal antibody, although demonstrated to inhibit the direct (transient) effects of TNFalpha on cartilage, exhibited no effect on blood-induced (prolonged) cartilage damage. It is demonstrated that IL-1beta is crucial in the development of blood-induced joint damage, whereas TNFalpha is not. This hierarchical position of IL-1beta in blood induced joint damage warrants studies on targeting IL-1beta to potentially prevent joint degeneration after a joint bleed. PMID- 26276669 TI - Molecular prediction of durable remission after first-line fludarabine cyclophosphamide-rituximab in chronic lymphocytic leukemia. AB - Fludarabine, cyclophosphamide, and rituximab (FCR) has represented a significant treatment advancement in chronic lymphocytic leukemia (CLL). In the new scenario of targeted agents, there is an increasing interest in identifying patients who gain the maximum benefit from FCR. In this observational multicenter retrospective analysis of 404 CLL patients receiving frontline FCR, the combination of three biomarkers that are widely tested before treatment (IGHV mutation status, 11q deletion and 17p deletion; available in 80% of the study cohort) allowed to identify a very low-risk category of patients carrying mutated IGHV genes but neither 11q or 17p deletion that accounted for 28% of all cases. The majority of very low-risk patients (71%) remained free of progression after treatment and their hazard of relapse decreased after 4 years from FCR. The life expectancy of very low-risk patients (91% at 5 years) was superimposable to that observed in the matched normal general population, indicating that neither the disease nor complications of its treatment affected survival in this favorable CLL group. These findings need a prospective validation and may be helpful for the design of clinical trials aimed at comparing FCR to new targeted treatments of CLL, and, possibly, for optimized disease management. PMID- 26276671 TI - Age of Entry Into Early Childhood Education and Care as a Predictor of Aggression: Faint and Fading Associations for Young Norwegian Children. AB - Socioemotional risks associated with nonparental care have been debated for decades, and research findings continue to be mixed. Yet few studies have been able to test the causal hypothesis that earlier, more extensive, and longer durations of nonmaternal care lead to more problems. To examine the consequences of age of entry into nonparental care for childhood aggression, we used prospective longitudinal data from Norway, where month of birth partly determines age of entry into Early Childhood Education and Care (ECEC) centers. In this sample of 939 children followed from ages 6 months through 4 years, ECEC teachers reported the children's aggression when they were 2, 3, and 4 years old. We found some evidence that age of entry into ECEC predicted aggression at age 2, albeit modestly and not robustly. Between the ages of 2 and 4 years, the effect of age of entry on aggression faded to negligible levels. The implications for psychological science and policy are discussed. PMID- 26276672 TI - Non-infectious in-cell HIV-1 protease assay utilizing translocalization of a fluorescent reporter protein and apoptosis induction. AB - This study describes a non-infectious in-cell imaging assay for HIV-1 protease inhibitor screening. It is based on re-distribution of a fluorescence reporter protein upon protease cleavage and the fact that HIV-infected cells undergo apoptosis. The in-cell assay utilizes fluorescent reporter proteins consisting of an intracellular translocation signal sequence, a caspase-3-specific cleavage sequence, and a fluorescent tagging protein. The reporter proteins are designed to change their intracellular localization upon cleavage, either from the cytosol to a subcellular organelle (type I) or from a subcellular organelle to the cytosol (type II). Inhibition of protease activity can be monitored at the single cell level. Interestingly, the expression of HIV-1 protease induced endogenous caspase-3 activation; thus, the fluorescence reporter protein containing the caspase-3 cleavage sequence translocalized upon cleavage. This is the first time that HIV-1 protease expression, not whole virus infection of the cell, was observed to trigger the apoptotic pathway, including caspse-3 activation. A validation of this assay was performed with a known HIV-1 protease inhibitor, Ac Leu-Val-phenylalanine. The clear cellular change in fluorescence pattern makes this system an ideal tool for various types of life science and drug discovery research, including high throughput and high content screening applications. PMID- 26276673 TI - Cornin increases angiogenesis and improves functional recovery after stroke via the Ang1/Tie2 axis and the Wnt/beta-catenin pathway. AB - We investigated whether cornin, an iridoid glycoside isolated from fruits of Verbena officinalis L., regulated angiogenesis and thereby improved functional outcomes after stroke and discovered a potential mechanism. The effects of cornin on proliferation of rat artery smooth muscle cell (RASMC) and signalling was investigated in vitro. Adult male rats were subjected to 1 h of middle cerebral artery occlusion (MCAO) and reperfusion and treated with or without 25 mg/kg of cornin, starting 24 h after ischemia and reperfusion, by continuous intravenous injection daily for 14 days. Neurological functional tests were performed and cerebral Evans blue extravasation was measured. Angiogenesis and angiogenic factor expressions were measured by immunohistochemistry and Western blotting, respectively. Cornin increased the proliferation of RASMC and enhanced the expression of Wnt5a, beta-catenin, cyclin D1 and angiopoietin-1 (Ang1). Cornin treatment promoted angiogenesis in the ischemic brain core and improved functional outcomes after stroke. Cornin-treated MCAO rats showed significant increase in vascularization and expression of vascular endothelial growth factor and Ang1 and phosphorylation of Tie2 and Akt compared with vehicle-treated MCAO rats. The Ang1/Tie2 axis and Wnt/beta-catenin pathways appear to mediate cornin induced angiogenesis. PMID- 26276675 TI - Allo-transplantation of mesenchymal stem cells attenuates hepatic injury through IL1Ra dependent macrophage switch in a mouse model of liver disease. AB - BACKGROUND & AIMS: Autologous transplantation of mesenchymal stem cells (MSCs) reduces concanavalin A (Con A)-induced hepatic injury in mice. However, the mechanism is unclear and the therapeutic effect of allo-transplantation remains unknown. Our aim was to investigate the effects and mechanisms related to allo transplantation of MSCs when used to treat Con A hepatic injury. METHODS: After Con A-induced liver injury was created in C57BL/6J mice, MSCs derived from BALB/c mice or a vehicle control was administered. RESULTS: Allo-transplantation of MSCs derived from BALB/c mice attenuated hepatic apoptosis in C57BL/6J mice that had undergone Con A-induced liver injury. MSCs increased the level of serum interleukin (IL)-10 and the phosphorylation of hepatic STAT3, but decreased the level of hepatic IFN-gamma and phospho-STAT1. Notably, the administered MSCs were trapped mostly in the lungs and promoted the macrophage M2 switch, which contributed to the increased IL10 levels in the lungs and serum. Loss of the therapeutic effect was observed after knock-down of the expression of interleukin 1 receptor antagonist (IL1Ra) in the MSCs. In vitro investigation supported the hypothesis that MSCs are able to switch Con A-stimulated macrophages to the M2 phenotype, which results in an increase in IL10 production. CONCLUSIONS: Allo transplantation of MSCs reduces Con A liver injury by increasing IL10 production through an IL1Ra dependent macrophage switch. PMID- 26276674 TI - Comparative Genomics of Environmental and Clinical Stenotrophomonas maltophilia Strains with Different Antibiotic Resistance Profiles. AB - Stenotrophomonas maltophilia, a ubiquitous Gram-negative gamma-proteobacterium, has emerged as an important opportunistic pathogen responsible for nosocomial infections. A major characteristic of clinical isolates is their high intrinsic or acquired antibiotic resistance level. The aim of this study was to decipher the genetic determinism of antibiotic resistance among strains from different origins (i.e., natural environment and clinical origin) showing various antibiotic resistance profiles. To this purpose, we selected three strains isolated from soil collected in France or Burkina Faso that showed contrasting antibiotic resistance profiles. After whole-genome sequencing, the phylogenetic relationships of these 3 strains and 11 strains with available genome sequences were determined. Results showed that a strain's phylogeny did not match their origin or antibiotic resistance profiles. Numerous antibiotic resistance coding genes and efflux pump operons were revealed by the genome analysis, with 57% of the identified genes not previously described. No major variation in the antibiotic resistance gene content was observed between strains irrespective of their origin and antibiotic resistance profiles. Although environmental strains generally carry as many multidrug resistant (MDR) efflux pumps as clinical strains, the absence of resistance-nodulation-division (RND) pumps (i.e., SmeABC) previously described to be specific to S. maltophilia was revealed in two environmental strains (BurA1 and PierC1). Furthermore the genome analysis of the environmental MDR strain BurA1 showed the absence of SmeABC but the presence of another putative MDR RND efflux pump, named EbyCAB on a genomic island probably acquired through horizontal gene transfer. PMID- 26276676 TI - Professionalism Redundant, Reshaped, or Reinvigorated? Realizing the "Third Logic" in Contemporary Health Care. AB - Recent decades have seen the influence of the professions decline. Lately, commentators have suggested a revived role for a "new" professionalism in ensuring and enhancing high-quality health care in systems dominated by market and managerial logics. The form this new professionalism might take, however, remains obscure. This article uses data from an ethnographic study of three English health care improvement projects to analyze the place, potential, and limitations of professionalism as a means of engaging clinicians in efforts to improve service quality. We found that appeals to notions of professionalism had strong support among practitioners, but converting enthusiasm for the principle of professionalism into motivation to change practice was not straightforward. Some tactics used in pursuit of this deviated sharply from traditional models of collegial social control. In systems characterized by fissures between professional groups and powerful market and managerial influences, we suggest that professionalism must interact creatively but carefully with other logics. PMID- 26276677 TI - High glucose-induced changes in hyaloid-retinal vessels during early ocular development of zebrafish: a short-term animal model of diabetic retinopathy. AB - BACKGROUND AND PURPOSE: Although a variety of animal models have been used to test drug candidates and examine the pathogenesis of diabetic retinopathy, time saving and inexpensive models are still needed to evaluate the increasing number of therapeutic approaches. EXPERIMENTAL APPROACH: We developed a model for diabetic retinopathy using the early stage of transgenic zebrafish (flk:EGFP) by treating embryos with 130 mM glucose, from 3-6 days post fertilisation (high glucose model). On day 6, lenses from zebrafish larvae were isolated and treated with 3% trypsin, and changes in hyaloid-retinal vessels were analysed using fluorescent stereomicroscopy. In addition, expression of tight junction proteins (such as zonula occludens-1), effects of hyperosmolar solutions and of hypoxia, and Vegf expression were assessed by RT -PCR. NO production was assessed with a fluorescent substrate. Effects of inhibitors of the VEGF receptor, NO synthesis and a VEGF antibody (ranibizumab) were also measured. KEY RESULTS: In this high glucose model, dilation of hyaloid-retinal vessels, on day 6, was accompanied by morphological lesions with disruption of tight junction proteins, overproduction of Vegf mRNA and increased NO production. Treatment of this high-glucose model with an inhibitor of VEGF receptor tyrosine kinase or an inhibitor of NO synthase or ranibizumab decreased dilation of hyaloid-retinal vessels. CONCLUSIONS AND IMPLICATIONS: These findings suggest that short-term exposure of zebrafish larvae to high-glucose conditions could be used for screening and drug discovery for diabetic retinopathy and particularly for disorders of retinal vessels related to disruption of tight junction proteins and excessive VEGF and NO production. PMID- 26276678 TI - A multiphase model for chemically- and mechanically- induced cell differentiation in a hollow fibre membrane bioreactor: minimising growth factor consumption. AB - We present a simplified two-dimensional model of fluid flow, solute transport, and cell distribution in a hollow fibre membrane bioreactor. We consider two cell populations, one undifferentiated and one differentiated, with differentiation stimulated either by growth factor alone, or by both growth factor and fluid shear stress. Two experimental configurations are considered, a 3-layer model in which the cells are seeded in a scaffold throughout the extracapillary space (ECS), and a 4-layer model in which the cell-scaffold construct occupies a layer surrounding the outside of the hollow fibre, only partially filling the ECS. Above this is a region of free-flowing fluid, referred to as the upper fluid layer. Following previous models by the authors (Pearson et al. in Math Med Biol, 2013, Biomech Model Mechanbiol 1-16, 2014a, we employ porous mixture theory to model the dynamics of, and interactions between, the cells, scaffold, and fluid in the cell-scaffold construct. We use this model to determine operating conditions (experiment end time, growth factor inlet concentration, and inlet fluid fluxes) which result in a required percentage of differentiated cells, as well as maximising the differentiated cell yield and minimising the consumption of expensive growth factor. PMID- 26276679 TI - Have Treatment Studies of Depression Become Even Less Generalizable? A Review of the Inclusion and Exclusion Criteria Used in Placebo-Controlled Antidepressant Efficacy Trials Published During the Past 20 Years. AB - OBJECTIVE: To compare the inclusion and exclusion criteria used in antidepressant efficacy trials (AETs) published during the past 5 years with those used in studies published during the previous 15 years. PATIENTS AND METHODS: We conducted a comprehensive literature review of placebo-controlled AETs published from January 1995 through December 2014. We included trials whether or not the medication has received regulatory approval for the treatment of depression. We compared the inclusion and exclusion criteria of studies published during the past 5 years (2010-2014) with those of studies published during the previous 15 years (1995-2009). RESULTS: We identified 170 placebo-controlled AETs published during the past 20 years, 56 of which were published during the past 5 years. The more recent studies were significantly more likely to exclude patients with comorbid Axis I disorders and personality disorders, patients with the episode duration either too long or too short, and patients who had made a suicide attempt in the past. The severity threshold on depression rating scales required for inclusion was higher in the more recent studies. CONCLUSION: The inclusion and exclusion criteria of AETs have become more stringent over the past 5 years, thereby suggesting that AETs may be even less generalizable than they were previously (when concerns about their generalizability had already been raised). PMID- 26276680 TI - Knowledge and beliefs about developmental dyslexia in pre-service and in-service Spanish-speaking teachers. AB - The present study investigated knowledge, misconceptions, and lack of information about dyslexia among pre-service (PST) and in-service (IST) Spanish-speaking teachers in Spain and Peru. Two hundred and forty-six pre-service teachers and 267 in-service teachers completed the Knowledge and Beliefs about Developmental Dyslexia Scale (KBDDS). In-service teachers scored significantly higher on the total scale, and on the symptoms/diagnosis and general information subscales, than pre-service teachers. The percentages for misconceptions and lack of information ("do not know responses") were higher for PSTs than for ISTs on the general information subscale, the symptoms/diagnosis subscale, and the treatment subscale. Analyses of individual items were conducted to differentiate concepts that teachers did not know from misconceptions. In-service teacher self-efficacy, years of teaching experience, post-graduate training in dyslexia, and prior exposure to a child with dyslexia were positively related to knowledge about dyslexia. Implications for pre-service teacher training and professional development are discussed. PMID- 26276682 TI - Gut microbiota composition associated with stool consistency. PMID- 26276681 TI - The role of growth differentiation factor 15 in the pathogenesis of primary myelofibrosis. AB - Growth differentiation factor 15 (GDF15) is a pleiotropic cytokine that belongs to the transforming growth factor-beta superfamily. Elevated serum concentrations of this cytokine have been reported in patients with various malignancies. To assess the potential roles of GDF15 in hematologic malignancies, we measured its serum levels in patients with these diseases. We found that serum GDF15 levels were elevated in almost all these patients, particularly in patients with primary myelofibrosis (PMF). Immunohistochemical staining of bone marrow (BM) specimens revealed that GDF15 was strongly expressed by megakaryocytes, which may be sources of increased serum GDF15 in PMF patients. Therefore, we further assessed the contribution of GDF15 to the pathogenesis of PMF. Recombinant human (rh) GDF15 enhanced the growth of human BM mesenchymal stromal cells (BM-MSCs), and it enhanced the potential of these cells to support human hematopoietic progenitor cell growth in a co-culture system. rhGDF15 enhanced the growth of human primary fibroblasts, but it did not affect their expression of profibrotic genes. rhGDF15 induced osteoblastic differentiation of BM-MSCs in vitro, and pretreatment of BM MSCs with rGDF15 enhanced the induction of bone formation in a xenograft mouse model. These results suggest that serum levels of GDF15 in PMF are elevated, that megakaryocytes are sources of this cytokine in BM, and that GDF15 may modulate the pathogenesis of PMF by enhancing proliferation and promoting osteogenic differentiation of BM-MSCs. PMID- 26276684 TI - Associations between reproduction and work in workers of the Asian hive bee Apis cerana. AB - If a honey bee (Apis spp.) colony becomes queenless, about 1/3 of young workers activate their ovaries and produce haploid male-producing eggs. In doing so queenless workers maximize their inclusive fitness because the normal option of vicarious production of relatives via their queen's eggs is no longer available. But if many workers are engaged in reproduction, how does a queenless colony continue to feed its brood and forage? Here we show that in the Asian hive bee Apis cerana hypopharyngeal gland (HPG) size is larger in queenless workers than in queenright workers and that bees undertaking brood-rearing tasks have larger HPG than same-aged bees that are foraging. In queenless colonies, workers with a smaller number of ovarioles are more likely to have activated ovaries. This reinforces the puzzling observation that a large number of ovarioles reduces reproductive success in queenless A. cerana. It further suggests that reproductive workers either avoid foraging or transition to foraging later in life than non-reproductive workers. Finally, our study also showed that ovary activation and larger-than-average numbers of ovarioles had no statistically detectable influence on foraging specialization for pollen or nectar. PMID- 26276683 TI - Host cell mTORC1 is required for HCV RNA replication. AB - OBJECTIVE: Chronically HCV-infected orthotopic liver transplantation (OLT) recipients appear to have improved outcomes when their immunosuppressive regimen includes a mammalian target of rapamycin (mTOR) inhibitor. The mechanism underlying this observation is unknown. DESIGN: We used virological assays to investigate mTOR signalling on the HCV replication cycle. Furthermore, we analysed HCV RNA levels of 42 HCV-positive transplanted patients treated with an mTOR inhibitor as part of their immunosuppressive regimen. RESULTS: The mTOR inhibitor rapamycin was found to be a potent inhibitor for HCV RNA replication in Huh-7.5 cells as well as primary human hepatocytes. Half-maximal inhibition was observed at 0.01 ug/mL, a concentration that is in the range of serum levels seen in transplant recipients and does not affect cell proliferation. Early replication cycle steps such as cell entry and RNA translation were not affected. Knockdown of raptor, an essential component of mTORC1, but not rictor, an essential component of mTORC2, inhibited viral RNA replication. In addition, overexpression of raptor led to higher viral RNA replication, demonstrating that mTORC1, but not mTORC2, is required for HCV RNA replication. In 42 HCV-infected liver-transplanted or kidney-transplanted patients who were switched to an mTOR inhibitor, we could verify that mTOR inhibition decreased HCV RNA levels in vivo. CONCLUSIONS: Our data identify mTORC1 as a novel HCV replication factor. These findings suggest an underlying mechanism for the observed benefits of mTOR inhibition in HCV-positive OLT recipients and potentiate further investigation of mTOR-containing regimens in HCV-positive recipients of solid organ transplants. PMID- 26276685 TI - Comparison of Changes in Anxiety and Depression Level Between Dabigatran and Warfarin Use in Patients With Atrial Fibrillation. AB - We hypothesized that patients taking warfarin require frequent hospital follow-up and they are at higher risk for complications, so the incidence of depression and anxiety is higher in patients with atrial fibrillation (AF) in the period of taking warfarin compared to the period of taking dabigatran. Fifty patients having AF without valvular diseases under treatment of warfarin in whom a transition to dabigatran was planned were consecutively enrolled in this study and followed up prospectively between July 2013 and July 2014. All patients completed Beck Depression Inventory and Hamilton Anxiety Scale (HAS) at the initiation of study and 6 months after initiation of study. Of the patients enrolled in the study, age, gender, smoking status, and comorbidities were questioned. A total of 50 patients (28 women; mean age 74.6 +/- 8.7 years) treated with warfarin in whom a transition to dabigatran was planned were included. Basal mean value of BDS (15.6 +/- 7.8 vs 11.5 +/- 4.8, P < .001) and HAS (16.8 +/- 10.4 vs 12.6 +/- 8.1, P < 0.001) was significantly higher in patients when they used warfarin than when they switched to dabigatran. In categorical analysis, frequency of patients with depression (mild, moderate, and severe) was significantly higher in period of warfarin use than after dabigatran transition (n = 24, 48% vs n = 14, 28%, P = .039). Our study demonstrates that patients with nonvalvular AF under treatment of dabigatran had lower BDS and HAS scores compared to warfarin. These findings suggest that dabigatran may increase quality of life and decrease morbidity and mortality due to reduction in anxiety and depression. PMID- 26276686 TI - Adenosine Diphosphate-Induced Platelets Aggregability in Polysomnographically Verified Obstructive Sleep Apnea. AB - Obstructive sleep apnea syndrome (OSAS) is a risk factor for arterial thrombosis and cardiovascular morbidity. Activated platelets play key roles in the development of atherothrombosis, thus may be involved in these complications of OSAS. Herein, we evaluated the relationship between severity of OSAS and the degree of platelet aggregates as a marker of activated platelets in 64 patients with OSAS. Platelet aggregations were determined by means of optical aggregometry, using adenosine diphosphate (ADP) as an agonist. Compared with the control group, ADP-induced platelet aggregability was increased in patients with total OSAS, severe OSAS, and in mild to moderate OSAS. Moreover, ADP-induced platelet aggregation was correlated with the Epworth sleepiness scale (ESS) in patients with severe OSAS. Obstructive sleep apnea syndrome is associated with enhanced platelets aggregations, which may predispose the cardiovascular sequels. The ESS may be important in predicting platelet activation and thus atherothrombotic complications in those with OSAS. PMID- 26276687 TI - Intussusception after monovalent rotavirus vaccine-United States, Vaccine Adverse Event Reporting System (VAERS), 2008-2014. AB - BACKGROUND: In 2006 and 2008, two new rotavirus vaccines (RotaTeq [RV5] and Rotarix [RV1]) were introduced in the United States. US data on intussusception have been mostly related to RV5, with limited data on RV1. METHODS: We assessed intussusception events following RV1 reported to the Vaccine Adverse Event Reporting System (VAERS), a US national passive surveillance system, during February 2008-December 2014. We conducted a self-controlled risk interval analysis using Poisson regression to estimate the daily reporting ratio (DRR) of intussusception after the first 2 doses of RV1 comparing average daily reports 3 6 versus 0-2 days after vaccination. We calculated the excess risk of intussusception per 100,000 vaccinations based on DRRs and background rates of intussusception. Sensitivity analyses were conducted to assess effects of differential reporting completeness and inaccuracy of baseline rates. RESULTS: VAERS received 108 confirmed insusceptible reports after RV1. A significant clustering was observed on days 3-8 after does1 (p=0.001) and days 2-7 after dose 2 (p=0.001). The DRR comparing the 3-6 day and the 0-2 day periods after RV1 dose 1 was 7.5 (95% CI=2.3, 24.6), translating to an excess risk of 1.6 (95% CI=0.3, 5.8) per 100,000 vaccinations. The DRR was elevated but not significant after dose 2 (2.4 [95% CI=0.8,7.5]). The excess risk ranged from 1.2 to 2.8 per 100,000 in sensitivity analysis. CONCLUSIONS: We observed a significant increased risk of intussusception 3-6 days after dose 1 of RV1. The estimated small number of intussusception cases attributable to RV1 is outweighed by the benefits of rotavirus vaccination. PMID- 26276690 TI - Esophageal Perforation Caused by Misplaced Minnesota Tube. PMID- 26276688 TI - A Structural View of Negative Regulation of the Toll-like Receptor-Mediated Inflammatory Pathway. AB - Even though the Toll-like receptor (TLR) pathway is integral to inflammatory defense mechanisms, its excessive signaling may be devastating. Cells have acquired a cascade of strategies to regulate TLR signaling by targeting protein protein interactions, or ubiquitin chains, but the details of the inhibition mechanisms are still unclear. Here, we provide the structural basis for the regulation of TLR signaling by constructing architectures of protein-protein interactions. Structural data suggest that 1) Toll/IL-1R (TIR) domain-containing regulators (BCAP, SIGIRR, and ST2) interfere with TIR domain signalosome formation; 2) major deubiquitinases such as A20, CYLD, and DUBA prevent association of TRAF6 and TRAF3 with their partners, in addition to removing K63 linked ubiquitin chains that serve as a docking platform for downstream effectors; 3) alternative downstream pathways of TLRs also restrict signaling by competing to bind common partners through shared binding sites. We also performed in silico mutagenesis analysis to characterize the effects of oncogenic mutations on the negative regulators and to observe the cellular outcome (whether there is/is not inflammation). Missense mutations that fall on interfaces and nonsense/frameshift mutations that result in truncated negative regulators disrupt the interactions with the targets, thereby enabling constitutive activation of the nuclear factor-kappa B, and contributing to chronic inflammation, autoimmune diseases, and oncogenesis. PMID- 26276689 TI - Parallel Allostery by cAMP and PDE Coordinates Activation and Termination Phases in cAMP Signaling. AB - The second messenger molecule cAMP regulates the activation phase of the cAMP signaling pathway through high-affinity interactions with the cytosolic cAMP receptor, the protein kinase A regulatory subunit (PKAR). Phosphodiesterases (PDEs) are enzymes responsible for catalyzing hydrolysis of cAMP to 5' AMP. It was recently shown that PDEs interact with PKAR to initiate the termination phase of the cAMP signaling pathway. While the steps in the activation phase are well understood, steps in the termination pathway are unknown. Specifically, the binding and allosteric networks that regulate the dynamic interplay between PKAR, PDE, and cAMP are unclear. In this study, PKAR and PDE from Dictyostelium discoideum (RD and RegA, respectively) were used as a model system to monitor complex formation in the presence and absence of cAMP. Amide hydrogen/deuterium exchange mass spectrometry was used to monitor slow conformational transitions in RD, using disordered regions as conformational probes. Our results reveal that RD regulates its interactions with cAMP and RegA at distinct loci by undergoing slow conformational transitions between two metastable states. In the presence of cAMP, RD and RegA form a stable ternary complex, while in the absence of cAMP they maintain transient interactions. RegA and cAMP each bind at orthogonal sites on RD with resultant contrasting effects on its dynamics through parallel allosteric relays at multiple important loci. RD thus serves as an integrative node in cAMP termination by coordinating multiple allosteric relays and governing the output signal response. PMID- 26276691 TI - [Error in cefotaxime dosage in some drug data sheets]. PMID- 26276692 TI - [CODEPEH 2014 recommendations for the early detection of delayed hearing loss]. AB - The latest scientific literature considers early diagnosis of deafness as key element to define the educational prognosis and inclusion of the deaf child, as advantage can be taken in the critical period of development (0-4 years). Highly significant differences exist between those deaf persons who have been stimulated early and those who have received late or inappropriate intervention. Early identification of late-onset disorders requires special attention and knowledge of all childcare professionals. Programs and additional actions beyond neonatal screening should be designed and planned in order to ensure that every child with a significant hearing loss is detected early. For this purpose, the Committee for the Early Detection of Deafness (CODEPEH) would like to highlight the need for continuous monitoring on the hearing health of children. And, for this reason, CODEPEH drafts the recommendations included in the present document. PMID- 26276693 TI - A plasma protein corona enhances the biocompatibility of Au@Fe3O4 Janus particles. AB - Au@Fe3O4 Janus particles (JPs) are heteroparticles with discrete domains defined by different materials. Their tunable composition and morphology confer multimodal and versatile capabilities for use as contrast agents and drug carriers in future medicine. Au@Fe3O4 JPs have colloidal properties and surface characteristics leading to interactions with proteins in biological fluids. The resulting protein adsorption layer ("protein corona") critically affects their interaction with living matter. Although Au@Fe3O4 JPs displayed good biocompatibility in a standardized in vitro situation, an in-depth characterization of the protein corona is of prime importance to unravel underlying mechanisms affecting their pathophysiology and biodistribution in vitro and in vivo. Here, we comparatively analyzed the human plasma corona of Au thiol@Fe3O4-SiO2-PEG JPs (NH2-functionalized and non-functionalized) and spherical magnetite (Fe3O4-SiO2-PEG) particles and investigated its effects on colloidal stability, biocompatibility and cellular uptake. Label-free quantitative proteomic analyses revealed that complex coronas including almost 180 different proteins were formed within only one minute. Remarkably, in contrast to spherical magnetite particles with surface NH2 groups, the Janus structure prevented aggregation and the adhesion of opsonins. This resulted in an enhanced biocompatibility of corona sheathed JPs compared to spherical magnetite particles and corona-free JPs. PMID- 26276694 TI - Neuroblastoma-targeted nanocarriers improve drug delivery and penetration, delay tumor growth and abrogate metastatic diffusion. AB - Selective tumor targeting is expected to enhance drug delivery and to decrease toxicity, resulting in an improved therapeutic index. We have recently identified the HSYWLRS peptide sequence as a specific ligand for aggressive neuroblastoma, a childhood tumor mostly refractory to current therapies. Here we validated the specific binding of HSYWLRS to neuroblastoma cell suspensions obtained either from cell lines, animal models, or Schwannian-stroma poor, stage IV neuroblastoma patients. Binding of the biotinylated peptide and of HSYWLRS-functionalized fluorescent quantum dots or liposomal nanoparticles was dose-dependent and inhibited by an excess of free peptide. In animal models obtained by the orthotopic implant of either MYCN-amplified or MYCN single copy human neuroblastoma cell lines, treatment with HSYWLRS-targeted, doxorubicin-loaded Stealth Liposomes increased tumor vascular permeability and perfusion, enhancing tumor penetration of the drug. This formulation proved to exert a potent antitumor efficacy, as evaluated by bioluminescence imaging and micro-PET, leading to (i) delay of tumor growth paralleled by decreased tumor glucose consumption, and (ii) abrogation of metastatic spreading, accompanied by absence of systemic toxicity and significant increase in the animal life span. Our findings are functional to the design of targeted nanocarriers with potentiated therapeutic efficacy towards the clinical translation. PMID- 26276695 TI - The short- and long-term effects of orally administered high-dose reduced graphene oxide nanosheets on mouse behaviors. AB - Reduced graphene oxide (rGO), a carbon-based nanomaterial, has enormous potential in biomedical research, including in vivo cancer therapeutics. Concerns over the toxicity remain outstanding and must be investigated before clinical application. The effect of rGO exposure on animal behaviors, such as learning and memory abilities, has not been clarified. Herein, we explored the short- and long-term effects of orally administered rGO on mouse behaviors, including general locomotor activity level, balance and neuromuscular coordination, exploratory and anxiety behaviors, and learning and memory abilities using open-field, rotarod, and Morris water maze tests. Compared with mice administered buffer-dispersed mouse chow or buffer alone, mice receiving a high dose of small or large rGO nanosheets showed little change in exploratory, anxiety-like, or learning and memory behaviors, although general locomotor activity, balance, and neuromuscular coordination were initially affected, which the mechanisms (e.g. the influence of rGO exposure on the activity of superoxide dismutase in mouse serum) were discussed. The results presented in this work look to provide a deep understanding of the in vivo toxicity of rGO to animals, especially its effect on learning and memory and other behaviors. PMID- 26276696 TI - Factors associated with recurrence after femoral derotation osteotomy in cerebral palsy. AB - Femoral derotation osteotomy (FDO) as gold standard treatment for internal rotation gait in cerebral palsy (CP) leads to satisfying short-term results, whereas rates of recurrence up to 33% are reported in long-term outcome studies. The purpose of this study was therefore to identify factors contributing to recurrence of internal rotation gait in patients with CP who were treated with FDO in childhood. 70 patients (age: 10 (+/- 3.3) years at surgery) with bilateral CP and internal rotation gait were examined pre-, one year and at least five years (mean 8 +/- 2 years) postoperatively after distal or proximal FDO, using standardized clinical examination and 3D gait-analysis. 27 patients had a good hip rotation one year postoperatively (between 5 degrees external and 15 degrees internal for both limbs) and were considered for the analysis of factors contributing to recurrence of internal rotation gait. Regarding all included patients both mean hip rotation and foot progression angle improved significantly (p < 0.001) from pre- to postoperative. A significant deterioration in hip rotation (more involved side) (p < 0.001) from one year postoperatively to the long-term follow-up can be observed. Younger age, reduced hip joint impulse, increased plantar flexion and internal foot progression angle postoperatively could be identified as factors for recurrence. FDO on average leads to a satisfactory correction of internal rotation gait. In order to improve the long term outcome after FDO the time of multilevel surgery should be indicated as late as possible and the different factors leading to potential recurrence should be considered. PMID- 26276697 TI - Malaria-associated morbidity during the rainy season in Saharan and Sahelian zones in Mauritania. AB - Reliable epidemiological data based on laboratory-confirmed cases are scarce in Mauritania. A large majority of reported malaria cases are based on presumptive clinical diagnosis. The present study was conducted to establish a reliable database on malaria morbidity among febrile paediatric and adult patients consulting spontaneously at public health facilities in Nouakchott, situated in the Saharan zone, and in Hodh Elgharbi region in the Sahelian zone in south-east Mauritania during the peak transmission periods. Giemsa-stained thin and thick films were examined under the microscope, and the parasite density was determined according to the procedures recommended by the World Health Organization. Microscopy results were confirmed by rapid diagnostic test for malaria. A total of 1161 febrile patients (498 in Nouakchott and 663 in Hodh Elgharbi region) were enrolled during two successive peak transmission periods in 2009 and 2010. In Nouakchott, 253 (50.8%) febrile patients had positive smears (83% Plasmodium vivax monoinfections and 17% Plasmodium falciparum monoinfections). In Hodh Elgharbi, 378 of 663 patients (57.0%) were smear-positive, mostly due to P. falciparum monoinfections (96.6%). Unlike in Nouakchott, mixed P. falciparum-P. vivax infections, as well as P. vivax, P. ovale, and P. malariae monoinfections, were also observed at a very low prevalence in southern Mauritania. In Nouakchott, malaria occurred more frequently (P<0.05) with higher slide positivity rates (42-53%) among children aged >5 years old and adults than in young children aged <5 years old in both 2009 and 2010. In Hodh Elgharbi, high slide positivity rates (60.9-86.2%) were observed in all age groups in 2010, and there was no significant trend (P>0.05) in relation with age groups. The present study confirmed the predominance of P. falciparum in southern Mauritania reported in previous studies. The presence of P. vivax in Nouakchott is a new epidemiological reality that requires an urgent adoption of novel strategies for parasitological and vector control to combat urban malaria. Moreover, the present study provides evidence-based data on malaria burden in two regions in Mauritania that may serve as a springboard to establish and develop a national surveillance system of malaria epidemiology. PMID- 26276698 TI - Taenia solium in Europe: Still endemic? AB - The pork tapeworm, Taenia solium, causes an important economic and health burden, mainly in rural or marginalized communities of sub-Saharan Africa, Asia, and Latin-America. Although improved pig rearing conditions seem to have eliminated the parasite in most Western European countries, little is known about the true endemicity status of T. solium throughout Europe. Three recent reviews indicate that autochthonous human T. solium taeniasis/cysticercosis may be possible in Europe, but that current peer-reviewed literature is biased towards Western Europe. Officially reported data on porcine cysticercosis are highly insufficient. Favourable conditions for local T. solium transmission still exist in eastern parts of Europe, although the ongoing integration of the European Union is speeding up modernisation and intensification of the pig sector. Further evidence is urgently needed to fill the gaps on the European T. solium endemicity map. We urge to make human cysticercosis notifiable and to improve the reporting of porcine cysticercosis. PMID- 26276699 TI - Unusual H-Bond Topology and Bifurcated H-bonds in the 2-Fluoroethanol Trimer. AB - By using a combination of rotational spectroscopy and ab initio calculations, an unusual H-bond topology was revealed for the 2-fluoroethanol trimer. The trimer exhibits a strong heterochiral preference and adopts an open OH???OH H-bond topology while utilizing two types of bifurcated H-bonds involving organic fluorine. This is in stark contrast to the cyclic OH???OH H-bond topology adopted by trimers of water and other simple alcohols. The strengths of different H-bonds in the trimer were analyzed by using the quantum theory of atoms in molecules. The study showcases a remarkable example of a chirality-induced switch in H-bond topology in a simple transient chiral fluoroalcohol. It provides important insight into the H-bond topologies of small fluoroalcohol aggregates, which are proposed to play a key role in protein folding and in enantioselective reactions and separations where fluoroalcohols serve as a (co)solvent. PMID- 26276700 TI - Functional connectivity measures as schizophrenia intermediate phenotypes: advances, limitations, and future directions. AB - The search for quantifiable biological mediators of genetic risk or 'intermediate phenotypes' is an essential strategy in psychiatric neuroscience and a useful tool for exploring the complex relationships between genes, neural circuits and behaviors. In recent years, the examination of connectivity-based intermediate phenotypes has gained increasing popularity in the study of schizophrenia, a brain disorder that manifests in early adulthood and disturbs a wide range of neural network functions. To date, several potential connectivity phenotypes have been identified that link neuroimaging measures of neural circuit interaction to genetic susceptibility for schizophrenia. This paper briefly reviews recent advances, current limitations and future directions in the search for functional connectivity intermediate phenotypes for schizophrenia across different cognitive domains. PMID- 26276701 TI - Influence of turbulent flow on the explosion parameters of micro- and nano aluminum powder-air mixtures. AB - The environmental turbulence intensity has a significant influence on the explosion parameters of both micro- and nano-Al at the time of ignition. However, explosion research on turbulence intensity with respect to micro- and nano-Al powders is still insufficient. In this work, micro- and nano-aluminum powders were investigated via scanning electron microscopy (SEM), and their particle size distributions were measured using a laser diffraction analyzer under dispersing air pressures of 0.4, 0.6, and 0.8 MPa in a 20 L cylindrical, strong plexiglass vessel. The particle size distributions in three different mass ratio mixtures of micro- and nano-Al powders (micro-Al:nano-Al[massratio]=95:5, 90:10, and 85:15) were also measured. The results show that the agglomerate size of nano-Al powder is an order of magnitude larger than the nanoparticles' actual size. Furthermore, the turbulence intensity ranges (Urms) of the Al powder-air mixtures were measured using particle image velocimetry (PIV) under dispersing air pressures of 0.4, 0.6, and 0.8 MPa. The effect of turbulence intensity on the explosion characteristics of the micro- and nano-Al powders was investigated using a 20 L cylindrical explosion vessel. The results of micro-Al and nano-Al powder-air mixtures with a stoichiometric concentration of 337.00 g.m(-3) were discussed for the maximum explosion pressure, the maximum rate of pressure increase and the maximum effective burning velocity under the different turbulence intensity. PMID- 26276702 TI - Environmental application of millimetre-scale sponge iron (s-Fe(0)) particles (III): The effect of surface silver. AB - To enhance the dechlorination reactivity of millimetric sponge iron (s-Fe(0)), a facile one-pot method was used to decorate s-Fe(0) with Ag(+) ions under ambient conditions. The results recorded by X-ray diffraction patterns, X-ray photoelectron spectra and high-resolution transmission electron microscopy demonstrated that the growth of Ag(0) was dominated primarily by (111) plane with a mean length of ~20 nm. The roles of Ag(0) loading, catalyst dosage, particle size, initial pH and contaminant concentration were assessed during the removal of pentachlorophenol (PCP). Catalyst recyclability was also studied. The results revealed that 3-5mm s-Fe(0) particles with 5 wt% Ag(0) loading exhibited the best performance with a dose of 3.0 g per 60 mL PCP solution. In addition, the dechlorination of PCP followed two-step, pseudo-first-order reaction kinetics, and Ag(0)-s-Fe(0) was advantageous compared with bimetals of nanoscale zero valent iron, iron power and iron flakes. The dechlorination mechanism of PCP over Ag(0)-s-Fe(0) was attributed to the surface Ag(0) decoration, which catalyzed the formation of reactive hydrogen atoms for indirect reaction, and the direct electron transfer via Fe-Ag(0) galvanic cells for direct reaction. This suggests that Ag-based bimetals of s-Fe(0) have great potential in the pretreatment of organic halogen compounds in aqueous solution. PMID- 26276703 TI - Cryptogenic mycotic aneurysm of the superior mesenteric artery. AB - Visceral artery aneurysms as a result of arterial degenerative disease are rare (0.1-2%), and superior mesenteric artery (SMA) accounts for 3.2% of all reported series. However, mycotic SMA aneurysms (SMAAs) are even rarer, and to the best of our knowledge, this is the first report of cryptogenic mycotic aneurysm of SMA by Enterococcus faecalis (EF). We report a case of 77-year-old man with 6-week history of supra pubic/left iliac fossa pain, weight loss and fever. The computed tomography demonstrated an incidental finding of 4.4 * 3-cm SMAA with no primary foci. The subsequent serology and specimen confirmed EF. Aneurysmectomy without bypass grafting along with antimicrobial therapy resulted in full recovery of the patient. PMID- 26276704 TI - Can adaptive treatment improve outcomes in family-based therapy for adolescents with anorexia nervosa? Feasibility and treatment effects of a multi-site treatment study. AB - OBJECTIVE: Adolescents with Anorexia Nervosa (AN), treated with family-based treatment (FBT) who fail to gain 2.3 kg by the fourth week of treatment have a 40 50% lower chance of recovery than those who do. Because of the high risk of developing enduring AN, improving outcomes in this group of poor responders is essential. This study examines the feasibility and effects of a novel adaptive treatment (i.e., Intensive Parental Coaching-IPC) aimed at enhancing parental self-efficacy related to re-feeding skills in poor early responders to FBT. METHOD: 45 adolescents (12-18 years of age) meeting DSM TR IV criteria for AN were randomized in an unbalanced design (10 to standard FBT; 35 to the adaptive arm). Attrition, suitability, expectancy rates, weight change, and psychopathology were compared between groups. OUTCOMES: There were no differences in rates of attrition, suitability, expectancy ratings, or most clinical outcomes between randomized groups. However, the group of poor early responders that received IPC achieved full weight restoration (>95% of expected mean BMI) by EOT at similar rates as those who had responded early. CONCLUSIONS: The results of this study suggest that it is feasible to use an adaptive design to study the treatment effect of IPC for those who do not gain adequate weight by session 4 of FBT. The results also suggest that using IPC for poor early responders significantly improves weight recovery rates to levels comparable to those who respond early. A sufficiently powered study is needed to confirm these promising findings. PMID- 26276705 TI - A proposed cascade of vascular events leading to granulomatous amoebic encephalitis. AB - Granulomatous amoebic encephalitis due to Acanthamoeba is a chronic disease that almost always results in death. Hematogenous spread is a pre-requisite followed by amoebae invasion of the blood-brain barrier to enter the central nervous system. Given the systemic nature of this infection, a significant latent period of several months before the appearance of clinical manifestations is puzzling. Based on reported cases, here we propose pathogenetic mechanisms that explain the above described latency of the disease. PMID- 26276706 TI - The diversities of staphylococcal species, virulence and antibiotic resistance genes in the subclinical mastitis milk from a single Chinese cow herd. AB - Staphylococci are the leading pathogens of bovine mastitis which is difficult to control. However, the published data on the prevalence of staphylococcal species, virulence and antibiotic resistance genes in bovine mastitis from China are limited. In this study, 104 out of 209 subclinical mastitis milk samples from a single Chinese dairy herd were cultured-positive for staphylococci (49.8%), which were further identified as coagulase-positive staphylococci (CPS) or coagulase negative staphylococci (CNS). According to the partial tuf and/or 16S rRNA gene sequence, the 28 CPS isolates were confirmed to be Staphylococcus aureus (26.9%), and 76 CNS isolates were assigned to 13 different species (73.1%) with Staphylococcus arlettae, Staphylococcus sciuri, Staphylococcus xylosus and Staphylococcus chromogenes as the dominant species. In the 28 S. aureus isolates, the most prevalent general virulence genes were coa, Ig and eno (100%), followed by hla (96.4%), hlb (92.9%), fib (92.9%), clfA (89.3%), clfB (85.7%) and nuc (85.7%). Both exotoxin and biofilm-associated genes were significantly less prevalent than the previously reported. Although 19 different virulence gene patterns were found, only one was dominant (32.1%). The prevalence of blaZ (82.1%) or mecA gene (35.7%) was much higher than the previously reported. In the 76 CNS isolates, the virulence genes were significantly less prevalent than that in the S. aureus isolates. Among the 4 main CNS species, S. chromogenes (n = 12) was the only species with high percentage (75%) of blaZ gene, while S. sciuri (n = 12) was the only species with the high percentage (66.7%) of mecA gene. The most of antibiotic resistance genes were present as multi-resistance genes, and the antibiotic resistances were attributed by different resistance genes between resistant S. aureus and CNS isolates. These data suggest that the prevalence of staphylococcal species, virulence and antibiotic resistance in the mastitis milk from the Chinese dairy herd are different from the previously reported, and that the herd- or farm-based diagnosis of staphylococcal bovine mastitis is required. PMID- 26276707 TI - Predicting eating disturbances in Turkish adult females: Examining the role of intimate partner violence and perfectionism. AB - We examined the relationships between intimate partner violence (IPV), perfectionism, and eating disturbances, namely, excessive dieting and bulimia, in a sample of 149 Turkish female college students. Results of conducting hierarchical regression analyses indicated that IPV accounted for significant variance in both excessive dieting and bulimic symptoms. The inclusion of perfectionism was found to predict additional variance in eating disturbances, beyond IPV. Specifically, we found parental expectations to be a significant predictor of dieting, and personal standards, doubts about actions, and parental criticism to be significant predictors of bulimia. Some implications for understanding eating disturbances in Turkish women are discussed. PMID- 26276708 TI - Illness anxiety and avoidant/restrictive food intake disorder: Cognitive behavioral conceptualization and treatment. AB - Eating difficulties are commonly present in medical and psychiatric settings. Some eating problems are resultant from fears about food consumption and can be conceptualized as anxiety disorders conditioned by perception of feared outcomes associated with eating and maintained by avoidance. The authors present a case in which a female patient with limited food intake is successfully treated with cognitive-behavioral therapy. Illness anxiety disorder and avoidant/restrictive food intake disorder, both newly included in DSM-V, are applied in this case. PMID- 26276709 TI - Executive function and mealtime behavior among preschool-aged children born very preterm. AB - OBJECTIVE: To determine whether executive function in preschool-aged children born very preterm was associated with problematic mealtime behavior. STUDY DESIGN: Executive function of 41 preschool-aged children (mean age=47 months) born at <30 weeks' gestation was assessed using a standardized protocol (gift bag) and by parent-report (Behavior Rating Inventory of Executive Function Preschool). The gift bag assessment was video-recorded and good executive function defined as the child not touching the gift bag and remaining seated for >2 min. Parent-reported frequency and severity of child mealtime behavior problems was assessed with a 20-item index (Meals in Our Household, alpha=0.94). Multivariable regression was used to model associations between executive function and mealtime behavior problems. RESULTS: BRIEF-P global executive composite t-scores [mean (standard deviation [SD])=53.5 (15.7)] and mealtime behavior problems scores [mean (SD) =18.5 (13.6)] were correlated (r=0.57, P<0.0001). Adjusted for child sex, age, birth weight, weeks' gestation, parent education, and neonatal intensive care unit length of stay, a 10-unit difference in BRIEF-P t-score was associated with a 7.2-unit difference in mealtime behavior problems score (P<0.0001). Ten children (24%) demonstrated good executive function during the gift bag assessment. Parents reported these children displayed better executive function on the BRIEF-P and had fewer mealtime behavior problems (mean 11.2 vs. 20.8, P=0.02). Adjusted for covariates, good performance on the gift bag task was associated with 14.1 unit lower mealtime behavior problems score (P=0.03). CONCLUSION: Among preschool-aged children born very preterm, difficulties with executive function may manifest as mealtime behavior problems. Larger studies are needed to help parents anticipate and manage these behaviors. PMID- 26276710 TI - Role of ellagic acid in regulation of apoptosis by modulating novel and atypical PKC in lymphoma bearing mice. AB - BACKGROUND: Protein kinase C regulates various cellular processes including cell proliferation, cell adhesion, apoptosis, angiogenesis, invasion, and metastasis. Activation of different PKC isozymes results in distinct cellular responses. Novel PKCs are mainly involved in apoptotic process. Atypical PKC subfamily plays a critical role in cell proliferation and apoptosis, cell differentiation and motility. However, Atypical PKCs show contradictory regulation in different tissues or cancer cells. The mechanism of diversified effects is not well explored. Antioxidant ellagic acid shows hepatoprotective, anti-carcinogenic and anti-mutagenic properties. Present study is focused to analyze the effect of ellagic acid on novel and atypical isozymes of PKC in regulation of PKC-mediated apoptosis in liver of lymphoma bearing mice. Implication of ellagic acid treatment to DL mice was analyzed on caspase-3 mediated apoptosis via PKCdelta induced activation; and on maintenance of adequate supply of energy during cancer growth. METHODS: 15-20 weeks old adult DL mice were divided into four groups (n=6). Group 2, 3, 4 were treated with different doses of ellagic acid (40 mg/kg, 60 mg/kg and 80 mg/kg bw). The mice were sacrificed after 19 days of treatment and liver was used for study. The effect of ellagic acid was determined on expression of novel and atypical PKC isozymes. Apoptotic potentiality of ellagic acid was checked on activities of caspase-3 and PKCdelta in terms of their catalytic fragments. Aerobic glycolysis was monitored by LDH activity, especially activity of LDH A. RESULTS: Ellagic acid treatment caused up regulation of expression of almost all novel and atypical PKC isozymes. Activities of PKCdelta and caspase-3 were enhanced by ellagic acid, however activities of total LDH and LDH-A were inhibited. CONCLUSION: The results show that ellagic acid promotes apoptosis in lymphoma bearing mice via novel and atypical PKCs which involves PKCdelta induced caspase-3 activation; and inhibition of glycolytic pathway. PMID- 26276712 TI - A novel truncated form of S100P predicts disease-free survival in patients with lymph node positive breast cancer. AB - The calcium-binding protein S100P is overexpressed in various cancers and may contribute to the oncogenic phenotype. This study used mass spectrometry to characterize a novel 9.2-kDa C-terminally truncated form of S100P (t-S100P), and to investigate its potential prognostic value in breast cancer. Univariate analysis demonstrated the association between breast tissue t-S100P levels (n = 148) and conventional pathological markers. Across all tumor samples, high t S100P was strongly prognostic for poor disease-free survival (P = 0.005), its efficacy confined to lymph node-positive tumors (n = 74, P = 0.007). Matrix assisted laser desorption/ionization imaging mass spectrometry confirmed differential t-S100P abundance between breast cancer and unaffected adjacent tissue. t-S100P was exclusively located in the cell nucleus of breast cancer tissue, and full-length S100P was essentially undetectable by mass spectrometry. We conclude that t-S100P is the predominant form of S100P in breast cancer tissue and is strongly prognostic for disease-free survival in women with lymph node positive disease. PMID- 26276711 TI - Sleep duration and sleep-disordered breathing and the risk of melanoma among US women and men. PMID- 26276713 TI - Tumor microenvironment: Sanctuary of the devil. AB - Tumor cells constantly interact with the surrounding microenvironment. Increasing evidence indicates that targeting the tumor microenvironment could complement traditional treatment and improve therapeutic outcomes for these malignancies. In this paper, we review new insights into the tumor microenvironment, and summarize selected examples of the cross-talk between tumor cells and their microenvironment, which have enhanced our understanding of pathophysiology of the microenvironment. We believe that this rapidly moving field promises many more to come, and they will guide the rational design of combinational therapies for success in cancer eradication. PMID- 26276714 TI - Podocalyxin-like protein 1 functions as an immunomodulatory molecule in breast cancer cells. AB - Podocalyxin-like protein 1 (PCLP1), a CD34-related sialomucin involved in the regulation of cellular morphology and adhesion, is expressed by a number of normal cells and various tumor cells. In breast malignancies PCLP1 overexpression has been associated with the most aggressive, metastatic cancers and poor prognosis. These observations suggest that PCLP1 expression could provide a mechanism to evade the immune response, thereby promoting metastatic progression of cancer. In the present work, we aimed to determine the effect of PCLP1 overexpressed in MCF7 breast cancer cells on natural killer (NK) cell cytotoxicity, dendritic cell maturation, and agonist-induced T cell proliferation. The results showed that PCLP1 expressed in MCF7 breast cancer cells confers resistance to NK cell-mediated cytolysis and impairs T cell proliferation. Furthermore, PCLP1 decreased the levels of NK cell activating receptors NKG2D, NKp30, NKp44, NKp46, DNAM-1, and CD16 on cell surface in a contact-dependent manner. Moreover, NK cells acquired PCLP1 from MCF7 cells by a process known as trogocytosis. These data reveal a new function of PCLP1 expressed on tumor cells as an immunomodulatory molecule, which may represent a mechanism to evade the immune response. PMID- 26276715 TI - Vitamin D and pancreatic cancer. AB - Pancreatic cancer is currently the fourth leading cause of cancer-related death, and it is projected that within the next two decades it will become the second most common cause of death due to cancer. Few patients are diagnosed when surgical resection is feasible and the efficacy of existing chemotherapeutic agents for advanced/metastatic cancer is limited. Thus, there is a need to identify agents that can prevent pancreatic cancer or improve survival in those affected. Vitamin D and its analogues, with their ability to regulate cell growth, differentiation, apoptosis and angiogenesis, may be promising agents. This review explores the published literature about the potential role of vitamin D and its analogues in preventing or treating pancreatic cancer. The vitamin D system is altered in pancreatic cancer. Pancreatic cancer tissue expresses vitamin D receptors, but the calcitriol analogues may affect pancreatic cancer tissue by mechanisms that do not involve interaction with its receptors. Experimental evidence postulates multiple potential mechanisms by which calcitriol analogues may exert their anti-cancer effect, the most common being by action on cyclin-dependent kinases p21 and p27. Use of calcitriol analogues in pancreatic cancer remains largely underexplored and warrants further clinical trials. PMID- 26276716 TI - Reprogramming cancer cells: a novel approach for cancer therapy or a tool for disease-modeling? AB - Chromatin dynamics have been the major focus of many physiological and pathological processes over the past 20 years. Epigenetic mechanisms have been shown to be reshaped during both cellular reprogramming and tumorigenesis. For this reason, cancer cell reprogramming can provide a powerful tool to better understand both regenerative and cancer-fate processes, with a potential to develop novel therapeutic approaches. Recent studies showed that cancer cells can be reprogrammed to a pluripotent state by the overexpression of reprogramming transcription factors. Activation of transcription factors and modification of chromatin regulators may result in the remodeling of epigenetic status and refueling of tumorigenicity in these reprogrammed cancer cells. However, studies focusing on cancer cell reprogramming are contradictory; some studies reported increased tumor progression whereas others showed that cellular reprogramming has a treatment potential for cancer. In this review, first, the current knowledge on the epigenetic mechanisms involved during cancer development and cellular reprogramming will be presented. Later, different reports and key factors about pluripotency-based reprogramming of cancer cells will be reviewed in detail. New insights will be provided on cancer biology and therapy in the light of cellular reprogramming. PMID- 26276717 TI - Integrated proteo-genomic approach for early diagnosis and prognosis of cancer. AB - Cancer is the leading cause of mortality among men and women worldwide. Despite the availability of numerous diagnostic techniques for various cancers, the overall survival rate remains low and the majority of patients die due to late diagnosis and advanced stage of the disease. Diagnosing and treating cancer at its early stages ideally during the precancerous phase could significantly increase survival rate with the possibility of cure and prolong survival. Cancer is a genetic disease and it is illicitly activated by the acquisition of somatic DNA lesions and aberrations in genome structure and defects in maintenance and repair. These somatic DNA mutations known as driver mutations seem to be the prime cause in initiating tumorigenesis. The advances in genomic technologies have immensely facilitated the understanding of cancer progression and metastasis, and the discovery of novel biomarkers. However, changes in somatic mutational landscape of the oncogenome are translated into aberrantly regulated oncoproteome which drives the cancer initiation. Thus, combination of proteomic and genomic technologies is urgently required to discover biomarkers for early diagnosis. The recent advances in human genome based detection of cancer using advanced genomic technologies like NextGen Sequencing, digital PCR, cfDNA technology have shown promise; for example oncogenic somatic mutation variants, transcriptomic analysis, copy number variant, and methylation data from the Cancer Genome Atlas. Similarly, oncoproteomics has the potential to revolutionize clinical management of the disease, including cancer diagnosis and screening based on new proteomic database which embodies somatic variants and post translational modifications, thus devising proteomic technologies as a complement to histopathology. Further, the use of multiple proteomic and genomic biomarkers rather than a single gene or protein could greatly improve diagnostic accuracy and enhance the predictive power for treatment outcome and may enable adequate monitoring of the response to treatment and could be an important option for personalized medicine. The proteogenomic approach has the promise to identify new biomarkers for radiation therapy (RT) which could reliably predict the tumor radiation resistance and which could also accurately predict normal tissue toxicity, and at the same time radiotherapy effectiveness. In this review we have summarize the recent advances in proteogenomic approaches to develop more sensitive diagnostic and prognostic biomarkers which could be translated into improved clinical care and management of the disease. PMID- 26276718 TI - Sonic hedgehog-glioma associated oncogene homolog 1 signaling enhances drug resistance in CD44(+)/Musashi-1(+) gastric cancer stem cells. AB - Drug resistance in gastric cancer largely results from the gastric cancer stem cells (GCSCs), which could be targeted to improve the efficacy of chemotherapy. In this study, we identified a subpopulation of GCSCs enriched in holoclones that expressed CD44(+)/Musashi-1(+) stem cell biomarkers, capable of self-renewal and proliferation. Enriched CD44(+)/Musashi-1(+) GCSCs demonstrated elevated expression of sonic hedgehog (SHH) and glioma-associated oncogene homolog 1 (GLI1), the well-known signaling pathway molecules involved in the drug resistance. Further, CD44(+)/Musashi-1(+) cells exhibited high drug efflux bump activity and were resistant to doxorubicin (Dox)-induced apoptosis, and unregulated the ATP-binding cassette sub-family G member 2 (ABCG2) expression,. The above effects on apoptosis were reversed in the presence of GLI inhibitors, GANT61 and GDC-0449, or by the knockdown of GLI1/SHH. Upon knockdown of GLI1, expression of ABCG2 was downregulated the antitumor effects were significantly improved as observed in the gastric cancer xenograft. Collectively, our study revealed that co-expression of CD44(+)/Musashi-1(+) could be used to identify GCSCs, which also accounts for the drug resistance in gastric cancer. SHH-GLI and its downstream effector ABCG2 could be better targeted to possibly improve the efficacy of chemotherapy in drug-resistant gastric cancers. PMID- 26276719 TI - Androgen receptor and antiandrogen therapy in male breast cancer. AB - Cancers arising in the male breast are uncommon. Male breast cancer is a hormone driven disease that often expresses the estrogen receptor, and antiestrogen therapy represents the mainstay of treatment. Paradoxically, the advent of a wave of antiestrogens eclipsed the therapeutic potential of alternative therapeutic options. At the beginning of the hormonal therapy era the administration of antiandrogens to metastatic male breast cancer patients was proposed. Ever since the use of these compounds has largely been neglected. A therapeutic role for antiandrogens has been envisioned again in recent years. First, molecular characterization efforts pointed to the androgen receptor as a potential therapeutic target. Second, the development of aromatase inhibitors unexpectedly raised the need for neutralizing androgens in order to tackle endocrine feedback mechanisms responsible for acquired resistance. We herein provide an overview of molecular studies where the androgen receptor was investigated at the genomic, transcriptomic or phenotypic level. We then discuss androgens in the context of the endocrine networks nourishing male breast cancer. Finally, clinical evidence on antiandrogens is summarized along with strategies should be implemented to improve the medical management of these patients. PMID- 26276720 TI - Dichotomous role of protein kinase A type I (PKAI) in the tumor microenvironment: a potential target for 'two-in-one' cancer chemoimmunotherapeutics. AB - An emerging trend in cancer chemoimmunotherapeutics is to develop 'two-in-one' therapies, which directly inhibit tumor growth and progression, as well as enhance anti-tumor immune surveillance. Protein kinase A (PKA) is a cAMP dependent protein kinase that mediates signal transduction of G-protein coupled receptors (GPCRs). The regulatory subunit of PKA exists in two isoforms, RI and RII, which distinguish the PKA isozymes, PKA type I (PKAI) and PKA type II (PKAII). The differential expression of both PKA isozymes has long been linked to growth regulation and differentiation. RI/PKAI is particularly implicated in cellular proliferation and neoplastic transformation. Emerging experimental and pre-clinical data also indicate that RI/PKAI plays a key role in tumor-induced immune suppression. More briefly, RI/PKAI possesses a dichotomous role in the tumor microenvironment: not only contributes to tumor growth and progression, but also takes part in tumor-induced suppression of the innate and adaptive arms of anti-tumor immunosurveillance. This review specifically discusses this dichotomous role of RI/PKAI with respect to 'two-in-one' chemoimmunotherapeutic manipulation. The reviewed experimental and pre-clinical data provide the proof of concept validation that RI/PKAI may be regarded as an attractive target for a new, single-targeted, 'two hit' chemoimmunotherapeutic approach against cancer. PMID- 26276721 TI - Circulating miRNAs revealed as surrogate molecular signatures for the early detection of breast cancer. AB - The miRNAs have well studied roles in cancer. Here, we identified altered miRNA expression by global miRNA profiling in peripheral blood mononuclear cells (PBMCs) of breast cancer (n = 15) and healthy subjects (n = 15), and further validated the selected miRNAs in PBMCs (n = 45), blood plasma (n = 45) and breast tissue samples (n = 09). The expression of altered miRNAs was also evaluated in PBMCs among early stage (n = 32), advanced stage (n = 13), triple positive (n = 5) and triple negative (n = 5) breast cancer patients. Results showed differential pattern of expressions of these miRNAs in multiple cohorts, however in early stage breast cancer, miR-106a-5p and miR-454-3p were upregulated (p < 0.05), miR-195-5p and miR-495 were downregulated (p < 0.05) in PBMCs. In addition, these miRNAs were also significantly associated with cancer and ErbB signaling pathways. Multiple regression analysis and receiver-operative curve (ROC) analysis of miR-195-5p and miR-495 with area under curve (AUC) of 0.901 showed best discriminating combination for early stage breast cancer detection. In summary, the present study delineated the importance of miR-195-5p and miR-495 miRNAs as prospective circulating surrogate molecular signatures for early detection of breast cancer. PMID- 26276722 TI - Identification of miRNomes in human stomach and gastric carcinoma reveals miR 133b/a-3p as therapeutic target for gastric cancer. AB - Gastric cancer (GC) is the fourth most frequent malignant disease and the second leading cause of cancer mortality worldwide, but the molecular mechanisms underlying this clinically heterogeneous disease are complex and remain far from completely understood. Accumulating evidence suggests that abnormal microRNA (miRNA) expression is involved in tumorigenesis. However, their accurate expression pattern, function, and mechanism in GC remain unclear. Here, a heatmap analysis of the miRNomes was performed across TCGA datasets and the expression of miR-133 family was found to be consistently downregulated in GC. This result was confirmed in two GC cell lines and 20 pairs of primary GC tissues, and further study demonstrated that the downregulation of miR-133 was mainly mediated by histone modification within its promoter region. Importantly, restoration of miR 133b/a-3p expression could suppress GC cell proliferation and promote cell apoptosis by targeting anti-apoptotic molecules Mcl-1 and Bcl-xL. Consistent with in vitro results, reintroducing of miR-133b/a-3p expression significantly delayed tumor formation and reduced tumor size of GC cells in xenograft nude mice. And the inverse relationship between miR-133b/a-3p and its targets was verified in xenograft mice. Taken together, our findings suggest that miR-133b/a-3p acts as a tumor suppressor in GC by directly targeting Mcl-1 and Bcl-xL. Revealing novel mechanism for oncogene inhibition by miRNA-mediated pathways offers new avenues for GC treatment. PMID- 26276723 TI - New insights into molecular diagnostic pathology of primary liver cancer: Advances and challenges. AB - Primary liver cancer (PLC) is one of the most common malignancies worldwide with increasing incidence and accounts for the third leading cause of cancer-related mortality. Traditional morphopathology primarily emphasizes qualitative diagnosis of PLC, which is not sufficient to resolve the major concern of increasing the long-term treatment efficacy of PLC in clinical management for the modern era. Since the beginning of the 21st century, molecular pathology has played an active role in the investigation of the evaluation of the metastatic potential of PLC, detection of drug targets, prediction of recurrence risks, analysis of clonal origins, evaluation of the malignancy trend of precancerous lesions, and determination of clinical prognosis. As a result, many new progresses have been obtained, and new strategies of molecular-pathological diagnosis have been formed. Moreover, the new types of pathobiological diagnosis indicator systems for PLC have been preliminarily established. These achievements provide valuable molecular pathology-based guide for clinical formulation of individualized therapy programs for PLC. This review article briefly summarizes some relevant progresses of molecular-pathological diagnosis of PLC from the perspective of clinical translational application other than basic experimental studies. PMID- 26276724 TI - Activated and expanded natural killer cells target osteosarcoma tumor initiating cells in an NKG2D-NKG2DL dependent manner. AB - Current therapies fail to cure most metastatic or recurrent bone cancer. We explored the efficacy and the pathways involved in natural killer (NK) cells' elimination of osteosarcoma (OS) cells, including tumor initiating cells (TICs), which are responsible for chemotherapy resistance, recurrence, and metastasis. The expression of ligands for NK cell receptors was studied in primary OS cell lines by flow cytometry. In vitro cytotoxicity of activated and expanded NK (NKAE) cells against OS was tested, and the pathways involved explored by using specific antibody blockade. NKAE cells' ability to target OS TICs was analyzed by flow cytometry and sphere formation assays. Spironolactone (SPIR) was tested for its ability to increase OS cells' susceptibility to NK cell lysis in vitro and in vivo. We found OS cells were susceptible to NKAE cells' lysis both in vivo and in vitro, and this cytolytic activity relied on interaction between NKG2D receptor and NKG2D ligands (NKG2DL). SPIR increased OS cells' susceptibility to lysis by NKAE cells, and could shrink the OS TICs. Our results show NKAE cells target OS cells including the TICs compartment, supporting the use of NK-cell based immunotherapies for OS. PMID- 26276725 TI - Toll-like receptor-4 is a target for suppression of proliferation and chemoresistance in HepG2 hepatoblastoma cells. AB - Toll-like receptor-4 (TLR4) is known to influence growth and migration of hepatocellular tumors; however, its role in hepatoblastoma remains poorly understood. This study investigated the regulatory role of TLR4 in proliferation and chemoresistance of HepG2 hepatoblastoma cells. Treatment with lipopolysaccharide (LPS), a TLR4 agonist, was found to significantly upregulate TLR4 expression in HepG2 cells, but not in malignant Huh-7 and Sk-Hep1 hepatocellular carcinoma cells. Additionally, IL-6 enhanced LPS-induced TLR4 upregulation. LPS-stimulated TLR4 activation increased proliferation, nitric oxide synthase (NOS) expression, and NO production in HepG2 cells. Chemotherapeutic agents, cisplatin and doxorubicin, effectively inhibited TLR4 expression in HepG2 cells. Characterization of LPS-induced signaling activation and blockade with kinase inhibitors revealed the involvement of Akt and MAPK pathways in LPS-enhanced NO release from, and proliferation of HepG2 cells. Mechanistically, gene modifications as a result of TLR4 transfection and siRNA mediated knockdown further demonstrated a crucial role for TLR4 in the regulation of NOS expression, cell proliferation, and chemoresistance in HepG2 cells. These findings suggest that targeting TLR4 expression and its cognate signaling may modulate proliferation and chemosensitivity in hepatoblastoma cells and serve as a potential therapeutic target. PMID- 26276726 TI - Combined IDH1 mutation and MGMT methylation status on long-term survival of patients with cerebral low-grade glioma. AB - OBJECTIVE: The management of low-grade glioma (LGG) still remains controversial because the effectiveness of early and extensive resection is unclear, and the use of radiation therapy or chemotherapy is not well-defined. In particular, the importance of prognostic factors for survival remains a matter of discussion. The purpose of this study was to validate prognostic factors for survival in patients with LGG. MATERIALS AND METHODS: A consecutive series of 55 patients with WHO grade II LGG treated in our institute between 1983 and 2013 were retrospectively reviewed to determine the prognostic factors for survival. All data were retrospectively analyzed from the aspect of baseline characteristics, pathological findings, genetic change, surgical treatments, adjuvant therapies, and survival time. Cox multivariate analysis was performed to determine the prognostic factors for survival. RESULTS: There were 28 patients with diffuse astrocytoma (DA), 21 patients with oligodendroglioma (OG), and 6 patients with oligoastrocytoma (OA) diagnosed on initial surgery. The median overall survival was 193 months and fifteen patients (27.3%) died. A mutation in isocitrate dehydrogenase-1 (IDH1) was found in 72.9% of LGG, and this mutation was positively correlated with methylation of O6-methylguanine-DNA methyltransferase (MGMT) (p=0.02). A better prognosis was significantly associated with combined IDH1 mutation and MGMT methylation status (both positive vs both negative, HR 0.079 [95% CI 0.008-0.579], p=0.012), as well as histology (OG vs DA and OA, HR 0.158 [95% CI 0.022-0.674], p=0.011) and tumor size (<6 cm vs >=6 cm, HR 0.120 [95% CI 0.017-0.595], p=0.008). CONCLUSIONS: Tumor histology, size and IDH mutation status are important predictors for prolonged overall survival in patients with LGG and may provide a reliable tool for standardizing future treatment strategies. PMID- 26276727 TI - Role of intraoperative indocyanine green video-angiography to identify small, posterior fossa arteriovenous malformations mimicking cavernous angiomas. Technical report and review of the literature on common features of these cerebral vascular malformations. AB - OBJECTIVE: To illustrate the usefulness of intraoperative indocyanine green videoangiography (ICG-VA) to identify the nidus and feeders of a small cerebellar AVM resembling a cavernous hemangioma. To review the unique features regarding the overlay between these two vascular malformations and to highlight the importance to identify with ICG-VA, and treat accordingly, the arterial and venous vessels of the AVM. METHODS: A 36-year old man presented with bilateral cerebellar hemorrhage. MRI was equivocal in showing an underlying vascular malformation but angiography demonstrated a small, Spetzler-Martin grade I AVM. Surgical resection of the AVM with the aid of intraoperative ICG-VA was performed. After hematoma evacuation, pre-resection ICG-VA did not reveal tortuous arterial and venous vessels in keeping with a typical AVM but rather an unusual blackberry-like image resembling a cavernous hemangioma, with tiny surrounding vessels. Such intraoperative appearance, which could also be the consequence of a "leakage" of fluorescent dye from the nidal pathological vessels, with absent blood-brain barrier, into the surrounding parenchymal pathological capillary network, is important to be recognized as an unusual AVM appearance. RESULTS: Post-resection ICG-VA confirmed the AVM removal, as also shown by postoperative and 3-month follow-up DSAs. CONCLUSIONS: Despite technical limitations associated with ICG-VA in post-hemorrhage AVMs, this case together with the intraoperative video, demonstrates the useful role of ICG-VA in identifying small AVMs with peculiar features. PMID- 26276728 TI - Improved survival after non-traumatic subarachnoid haemorrhage with structured care pathways and modern intensive care. AB - OBJECTIVE: Patients with subarachnoid haemorrhage (SAH) often require multidisciplinary management and their treatment is difficult to standardize. The aim was to describe baseline characteristics, care pathways and discharge status in an unselected group of patients with first ever non-traumatic SAH, and to examine whether their care pathways and outcomes vary. METHODS: Patients admitted with first ever non-traumatic SAH to a neurosurgical unit (NSU) in Sweden during a period of 18 months in 2009-2010 were included. The data was retrospectively collected from patient charts. RESULTS: A total of 131 patients were admitted with first ever non-traumatic SAH. Forty-nine (37%) patients initially sought medical care nearby the NSU and 82 (63%) in other parts of the catchment area. The average age was 55.5 years and 79 (60%) were female. In 98 (75%) cases, a ruptured aneurysm was found to be the cause of SAH. There was a significant correlation between poor clinical grade at admission and poor patient outcome (p<0.0005). No significant correlation between early aneurysm treatment and improved clinical outcome were seen. No significant differences in outcome were seen between patients who initially sought medical care nearby the NSU and those in other parts of the catchment area. There was no difference seen in the number of patients who had follow-up at the NSU depending on where they initially sought help. CONCLUSION: This study shows an improvement in survival after SAH compared to earlier studies in Sweden. The results are indicative of effective management of all patients with SAH in the catchment area that are treated at the NSU. A nationwide registry to assess the overall management of patients treated for SAH would be useful to further investigate patients with SAH. PMID- 26276729 TI - Study of Spirituality in Elderly With Subjective Memory Complaints. AB - Subjective memory complaints are very common among elderly. They can be due to depression, cognitive decline, or be a part of normal aging process. Spirituality is another important dimension in elderly, and it is believed to help them cope with various adversities. This study was done to find out whether any relation exists between these 2 variables in elderly. A total of 120 elderly individuals, presenting with subjective memory complaints, were divided into 3 groups - controls, elderly with depression, and elderly with mild cognitive impairment (MCI). Spirituality in them was studied by dividing it into the subdomains of self-transcendence, presence of meaning in life, search for meaning in life, and locus of control. Spirituality was the highest in controls, followed by MCI group, and then depression group. Spirituality had a direct negative relationship with severity of depression, while relationship of spirituality with severity of cognitive decline was more complex. Relationship of spirituality with mental health status in elderly patients seemed bidirectional, that is, cause as well as effect relationship. PMID- 26276730 TI - Acute neck pain caused by septic arthritis of the lateral atlantoaxial joint with subluxation: a case report. AB - INTRODUCTION: Crystal-induced arthritis of the lateral atlantoaxial joint may be intimately involved in acute neck pain in the elderly. Patients typically have a good prognosis, and symptoms usually subside within a few weeks. On the other hand, septic arthritis of the lateral atlantoaxial joint requires early diagnosis and antibiotic treatment. Diagnostic delay is a risk factor for an unfavorable outcome of vertebral osteomyelitis. Even though septic arthritis of the lateral atlantoaxial joint is a very rare clinical entity, it is important to differentiate septic arthritis from crystal-induced arthritis. CASE PRESENTATION: A 53-year-old Japanese man presented with neck pain, stiffness, and loss of power of his left upper extremity which started 20 days before his visit to our hospital. A physical examination revealed a limited range of motion of his neck, with rotation being especially very restricted. Atlantoaxial subluxation was seen on plain radiography of his cervical spine. During puncture of the lateral atlantoaxial joint, clear yellow fluid was collected. Cultures later grew methicillin-sensitive Staphylococcus aureus. He was diagnosed with septic arthritis of the lateral atlantoaxial joint with atlantoaxial subluxation. After diagnosis, intravenous administration of antibiotics was begun. The atlantoaxial region was stabilized with the Brooks procedure. Plain radiography showed complete bone union 8 months after operation. At a follow-up evaluation 7 years after initial onset, he had complete relief of neck pain, and there were no neurological abnormalities. CONCLUSIONS: A patient with septic arthritis of the lateral atlantoaxial joint with subluxation presenting with acute neck pain was successfully treated with antibiotics and fusion surgery. In patients with persistent neck pain, septic arthritis of the lateral atlantoaxial joint should be considered and further examinations performed. PMID- 26276731 TI - A systematic evaluation of three different cardiac T2-mapping sequences at 1.5 and 3T in healthy volunteers. AB - BACKGROUND: Previous studies showed that myocardial T2 relaxation times measured by cardiac T2-mapping vary significantly depending on sequence and field strength. Therefore, a systematic comparison of different T2-mapping sequences and the establishment of dedicated T2 reference values is mandatory for diagnostic decision-making. METHODS: Phantom experiments using gel probes with a range of different T1 and T2 times were performed on a clinical 1.5T and 3T scanner. In addition, 30 healthy volunteers were examined at 1.5 and 3T in immediate succession. In each examination, three different T2-mapping sequences were performed at three short-axis slices: Multi Echo Spin Echo (MESE), T2 prepared balanced SSFP (T2prep), and Gradient Spin Echo with and without fat saturation (GraSEFS/GraSE). Segmented T2-Maps were generated according to the AHA 16-segment model and statistical analysis was performed. RESULTS: Significant intra-individual differences between mean T2 times were observed for all sequences. In general, T2prep resulted in lowest and GraSE in highest T2 times. A significant variation with field strength was observed for mean T2 in phantom as well as in vivo, with higher T2 values at 1.5T compared to 3T, regardless of the sequence used. Segmental T2 values for each sequence at 1.5 and 3T are presented. CONCLUSIONS: Despite a careful selection of sequence parameters and volunteers, significant variations of the measured T2 values were observed between field strengths, MR sequences and myocardial segments. Therefore, we present segmental T2 values for each sequence at 1.5 and 3T with the inherent potential to serve as reference values for future studies. PMID- 26276732 TI - Anti-nociceptive and anti-inflammatory activities of 4-[(1-phenyl-1H-pyrazol-4 yl) methyl] 1-piperazine carboxylic acid ethyl ester: A new piperazine derivative. AB - Piperazine compounds possess anti-infective, anti-carcinogenic, anxiolytic, hypotensive, anti-hypertensive and vasorelaxant properties and are attractive candidates for the development of new analgesic and anti-inflammatory drugs. This study investigates the anti-nociceptive and anti-inflammatory effects of piperazine derivative 4-[(1-phenyl-1H-pyrazol-4-yl) methyl]1-piperazine carboxylic acid ethyl ester (LQFM-008) and the involvement of the serotonergic pathway. In the formalin test, treatments with LQFM-008 (15 and 30mg/kg p.o.) reduced the licking time in both neurogenic and inflammatory phases of this test. In the tail flick and hot plate tests, LQFM008 treatment (15 and 30mg/kg p.o.) increased latency to thermal stimulus, suggesting the involvement of central mechanisms in the anti-nociceptive effect of LQFM-008. In the carrageenan-induced paw edema test, LQFM-008 (p.o.) at the doses of 15 and 30mg/kg reduced the edema at all tested time points, while the dose of 7.5mg/kg reduced the edema only for the first hour. LQFM-008 (30mg/kg p.o.) reduced both cell migration and protein exudation in the carrageenan-induced pleurisy test. Furthermore, pre-treatment with NAN-190 (0.6mg/kgi.p.) and PCPA (100mg/kgi.p.) antagonized the anti nociceptive effect of LQFM-008 in both phases of the formalin test. Our data suggest that LQFM-008 possesses anti-inflammatory and anti-nociceptive effects mediated through the serotonergic pathway. PMID- 26276733 TI - Prevalence and spatial distribution of bovine brucellosis in San Luis and La Pampa, Argentina. AB - BACKGROUND: Bovine brucellosis (BB) is a zoonotic disease caused by Brucella abortus. BB is endemic in Argentina, where vaccination with Brucella abortus strain 19 is compulsory for 3-to-8 month-old heifers. The objectives of this study were to quantify the prevalence of BB and to identify factors associated with its occurrence, along with the spatial distribution of the disease, in the provinces of La Pampa and San Luis. A two-stage random sampling design was used to sample 8,965 cows (3,513 in La Pampa and 5,452 in San Luis) from 451 farms (187 in La Pampa and 264 in San Luis). RESULTS: Cow and herd prevalence were 1.8 % (95 % CI: 1.3-2.2; n = 157) and 19.7 % (95 % CI: 17.0-22.4; n = 89), respectively. Both cow-level and herd-level prevalence in La Pampa (2.4 and 26.0 %, respectively) were significantly higher than in San Luis (1.4 and 15.5 %, respectively). There were not differences between the proportions of reactive cattle compared to that obtained in a survey conducted in 2005. However, herd prevalence in La Pampa was significantly (P < 0.05) higher compared to that study. Disease was found to be spatially clustered in west La Pampa. The lower the bovine density and the calf/cow ratio, the higher odds of belonging to the cluster. CONCLUSIONS: The increase of farm prevalence in the last five years suggests that the disease is spreading and that control measures should be applied in the region. The cluster of infected farms was located in the west region of La Pampa. There, farms have lower animal densities and smaller cow/calf indices compared to the rest of the province. Although western La Pampa has more infected herds, within-farm prevalence was not higher, which suggests that the control program has been relatively successful in controlling the disease at the farm level, and/or that low animal density inherently results in low disease prevalence. Our results provide baseline information on the epidemiology of BB and its potential pattern of transmission in Argentina, which will ultimately help to improve BB control programs in the country. PMID- 26276734 TI - Impact of waiting time after surgery and overall time of postoperative radiochemotherapy on treatment outcome in glioblastoma multiforme. AB - BACKGROUND: A time factor of radiooncological treatment has been demonstrated for several tumours, most prominently for head and neck squamous cell carcinoma and lung cancer. In glioblastoma multiforme studies of the impact of postoperative waiting times before initiation of radio- or radiochemotherapy were inconclusive. Moreover analysis of the impact of overall treatment time of radiochemotherapy as well as overall duration of local treatment from surgery to the end of radiochemotherapy is lacking to date. METHODS: In this retrospective cohort study, we included 369 consecutive patients treated at our institution between 2001 and 2014. Inclusion criteria were histologically proven glioblastoma multiforme, age >= 18 years, ECOG performance status 0-2 before radiotherapy, radiotherapy or radiochemotherapy with 33 * 1.8 Gy to 59.4 Gy or with 30 * 2.0 Gy to 60 Gy. The impact of postoperative waiting time, radiation treatment time and overall duration of local treatment from surgery to the end of radiotherapy on overall (OS) and progression-free (PFS) survival were evaluated under consideration of known prognostic factors by univariate Log-rank tests and multivariate Cox-regression analysis. RESULTS: The majority of patients had received simultaneous and further adjuvant chemotherapy, mainly with temozolomide. Median survival time and 2-year OS were 18.0 months and 38.9% after radiochemotherapy compared to 12.7 months and 12.6% after radiotherapy alone. Median progression-free survival time was 7.5 months and PFS at 2 years was 14.3% compared to 6.0 months and 3.3%, respectively. Significant prognostic factors in multivariate analysis were age, resection status and application of simultaneous chemotherapy. No effect of the interval between surgery and adjuvant radiotherapy (median 27, range 11-112 days), radiation treatment time (median 45, range 40-71 days) and of overall time from surgery until the end of radiotherapy (median 54, range 71-154 days) on overall and progression-free survival was evident. CONCLUSION: Our data do not indicate a relevant time factor in the treatment of glioblastoma multiforme in a large contemporary single-centre cohort. Although this study was limited by its retrospective nature, its results indicate that short delays of postoperative radiochemotherapy, e.g. for screening of a patient for a clinical trial, may be uncritical. PMID- 26276735 TI - Mechanisms of lapatinib resistance in HER2-driven breast cancer. AB - Targeted therapies have been approved for various malignancies but the acquisition of resistance remains a substantial challenge in the clinical management of advanced cancers. Twenty-five per cent of breast cancers overexpress ErbB2/HER2, which confers a more aggressive phenotype and is associated with a poor prognosis. HER2-targeting therapies (trastuzumab, pertuzumab, TDM1 and lapatinib) are available, but a significant fraction of HER2 positive breast cancers eventually relapse or progress. This suggests that acquired or intrinsic resistance enables escape from HER2 inhibition. This review focuses on mechanisms of intrinsic/acquired resistance to lapatinib identified in preclinical and clinical studies. A better understanding of these mechanisms could lead to novel predictive markers of lapatinib response and to novel therapeutic strategies for breast cancer patients. PMID- 26276736 TI - [MAPEX: look deeper, looking away]. PMID- 26276737 TI - [The impact of Pharmacy Intervention on the treatment of elderly multi pathological patients]. AB - OBJECTIVE: to analyze the impact of Pharmacy Intervention (PI), within the healthcare team who manages elderly multi-pathological patients, regarding the evolution of Drug Related Problems (DRPs) and Negative Outcomes Associated with Medication (NOMs). To estimate the prevalence of DRPs, NOMs, and Potentially Inappropriate Prescriptions (PIPs), and the drugs involved, considering the characteristics of their healthcare location. METHOD: multicenter, prospective study, on > 65-year-old patients with multiple pathologies, either institutionalized or hospitalized. The Pharmacist reviewed the chronic medication of the patient in order to detect DRPs and NOMs, and issued recommendations to the physician responsible for the patient, and this intervention was subsequently evaluated. DRPs and NOMs were classified according to the Third Consensus of Granada. The STOPP/START Criteria were used for PIP detection. The primary variables were: number of PIs conducted and accepted by the physician. OUTCOMES: 338 patients were included, and 326 (96.4%) presented some DRP. 1089 DRPs were detected, with 983 PIs suggested for their solution, and 651 (69.9%) of these were accepted. PIs solved 58.9% of DRPs, and an association was found between PI and the solution for the DRP (p < 0.001). PIs were more accepted in institutionalized than in hospitalized patients (p = 0.002), by physicians with a higher specialization (p < 0.001) and when they involved quantitative safety NOMs (p = 0.042). The STOPP/START Criteria detected 65% of PIPs, and more PIPs not associated with these criteria were found in institutionalized than in hospitalized patients (p < 0.001). CONCLUSIONS: pharmacy Intervention within the multidisciplinary team can solve in a significant way both DRPs and NOMs in elderly multi-pathological patients, and thus help to improve the quality of their pharmacological therapy. This is the first multicenter clinical trial with these characteristics that has been conducted in Spain. PMID- 26276738 TI - [Oral chemotherapy: food-drug interactions]. AB - INTRODUCTION: oral chemotherapy is increasingly used in Oncology. It has important advantages. such as patient comfort. but it also brings new challenges which did not exist with the intravenous therapy. Some of these drugs have interactions with food. leading to changes in their bioavailability. As they are drugs of narrow therapeutic margin. this can lead to alterations in their efficacy and/or toxicity. OBJECTIVES: A. Assessing the level of knowledge on the administration of oral cytostatics that present restrictions with meals (drugs that have to be taken with/without food) among the outpatients. B. Minimizing the incorrect administration and the risk of food-drug interactions. providing patients with information as to how and when drugs have to be administrated. METHODS: once the oral cytostatics with food restrictions were identified. we asked the patients in treatment about the information they had received from the doctor and the way they were taking the medication. We provided those who were taking the drug incorrectly with the right information. In the following visit. it was confirmed if the patients that had been previously taking the cytostatic incorrectly. were taking them in a correct way (intervention accepted/not accepted). RESULTS AND CONCLUSIONS: 40% of the patients interviewed used to take the drug incorrectly. We detected a great diversity depending on the dispensed drug. 95% of the 39 interventions made were accepted. The data obtained suggest the need to reinforce the information that the patient receives. It is important to make sure that the patient understands how and when the oral cytostatic should be administered. PMID- 26276739 TI - [Applying dose banding to the production of antineoplastic drugs: a narrative review of the literature]. AB - The dosage of antineoplastic drugs has historically been based on individualized prescription and preparation according to body surface area or patient's weight. Lack of resources and increased assistance workload in the areas where chemotherapy is made, are leading to the development of new systems to optimize the processing without reducing safety. One of the strategies that has been proposed is the elaboration by dose banding. This new approach standardizes the antineoplastic agents doses by making ranges or bands accepting a percentage of maximum variation. It aims to reduce processing time with the consequent reduction in waiting time for patients; to reduce errors in the manufacturing process and to promote the rational drug use. In conclusion, dose banding is a suitable method for optimizing the development of anticancer drugs, obtaining reductions in oncologic patients waiting time but without actually causing a favorable impact on direct or indirect costs. PMID- 26276740 TI - [Eculizumab for atypical hemolytic uremic syndrome in newborn: a case report]. PMID- 26276741 TI - [Vancomycin intoxication in a patient with inappropriate antidiuretic hormone syndrome and diarrhea]. AB - Vancomycin is an antibiotic used for infections by gram-positive bacteria with a two-compartment pharmacokinetic model. Its monitoring has an established therapeutic range (10-20 mg/L) to prevent nephrotoxicity and ototoxicity due to supratherapeutic levels, and inefficiency and development of resistance by subtherapeutic levels. Nephrotoxicity for vancomycin monotherapy at standard doses according to pathogen and typical regimens (usual dose: 15-20 mg/kg/12 h) is rare and usually reversible. Moreover, monitoring plasma concentrations allows to achieve concentrations within therapeutic range to allow safe and effective drug use. The renal hypoperfusion can cause pre-renal damage, resulting in elevated levels of serum creatinine, resulting in decreased antibiotic elimination and nephrotoxicity. We report a case of unexpected vancomycin nephrotoxicity in a patient with syndrome Inappropriate antidiuretic hormone secretion associated paraneoplastic. PMID- 26276742 TI - [Off-lable uses of mycophenolate mofetil: lupus nephritis]. PMID- 26276743 TI - [Impact of the economic crisis on the activity of a clinical research ethics committee; response from the Spanish Agency of Medicines and Medical Devices]. PMID- 26276744 TI - Modulation of Breast Cancer Risk Biomarkers by High-Dose Omega-3 Fatty Acids: Phase II Pilot Study in Postmenopausal Women. AB - Associational studies suggest higher intakes/blood levels of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) relative to the omega-6 arachidonic acid (AA) are associated with reduced breast cancer risk. We performed a pilot study of high-dose EPA + DHA in postmenopausal women to assess feasibility before initiating a phase IIB prevention trial. Postmenopausal women with cytologic evidence of hyperplasia in their baseline random periareolar fine needle aspiration (RPFNA) took 1,860 mg EPA +1500 mg DHA ethyl esters daily for 6 months. Blood and breast tissue were sampled at baseline and study conclusion for exploratory biomarker assessment, with P values uncorrected for multiple comparisons. Feasibility was predefined as 50% uptake, 80% completion, and 70% compliance. Trial uptake by 35 study entrants from 54 eligible women was 65%, with 97% completion and 97% compliance. Favorable modulation was suggested for serum adiponectin (P = 0.0027), TNFalpha (P = 0.016), HOMA 2B measure of pancreatic beta cell function (P = 0.0048), and bioavailable estradiol (P = 0.039). Benign breast tissue Ki-67 (P = 0.036), macrophage chemoattractant protein-1 (P = 0.033), cytomorphology index score (P = 0.014), and percent mammographic density (P = 0.036) were decreased with favorable effects in a proteomics array for several proteins associated with mitogen signaling and cell cycle arrest; but no obvious overall effect on proteins downstream of mTOR. Although favorable risk biomarker modulation will need to be confirmed in a placebo-controlled trial, we have demonstrated feasibility for development of high-dose EPA and DHA ethyl esters for primary prevention of breast cancer. PMID- 26276745 TI - Vitamin D Repletion Reduces the Progression of Premalignant Squamous Lesions in the NTCU Lung Squamous Cell Carcinoma Mouse Model. AB - The chemopreventive actions of vitamin D were examined in the N-nitroso-tris chloroethylurea (NTCU) mouse model, a progressive model of lung squamous cell carcinoma (SCC). SWR/J mice were fed a deficient diet (D) containing no vitamin D3, a sufficient diet (S) containing 2,000 IU/kg vitamin D3, or the same diets in combination with the active metabolite of vitamin D, calcitriol (C; 80 MUg/kg, weekly). The percentage (%) of the mucosal surface of large airways occupied by dysplastic lesions was determined in mice after treatment with a total dose of 15 or 25 MUmol NTCU (N). After treatment with 15 MUmol NTCU, the percentages of the surface of large airways containing high-grade dysplastic (HGD) lesions were vitamin D-deficient + NTCU (DN), 22.7% [P < 0.05 compared with vitamin D sufficient +NTCU (SN)]; DN + C, 12.3%; SN, 8.7%; and SN + C, 6.6%. The extent of HGD increased with NTCU dose in the DN group. Proliferation, assessed by Ki-67 labeling, increased upon NTCU treatment. The highest Ki-67 labeling index was seen in the DN group. As compared with SN mice, DN mice exhibited a three-fold increase (P < 0.005) in circulating white blood cells (WBC), a 20% (P < 0.05) increase in IL6 levels, and a four-fold (P < 0.005) increase in WBC in bronchial lavages. Thus, vitamin D repletion reduces the progression of premalignant lesions, proliferation, and inflammation, and may thereby suppress development of lung SCC. Further investigations of the chemopreventive effects of vitamin D in lung SCC are warranted. PMID- 26276746 TI - Low SFRP1 Expression Correlates with Poor Prognosis and Promotes Cell Invasion by Activating the Wnt/beta-Catenin Signaling Pathway in NPC. AB - Distant metastasis remains the predominant mode of treatment failure in nasopharyngeal carcinoma (NPC). Unfortunately, the molecular events underlying NPC metastasis remain poorly understood. Secreted frizzled-related protein 1 (SFRP1) plays an important role in tumorigenesis and progression. However, little is known about the function and mechanism of SFRP1 in NPC. Immunohistochemistry was used to determine SFRP1 expression levels in patients with NPC. SFRP1 function was evaluated using MTT, colony formation, wound-healing, Transwell assays, and in vivo models. The methylation level of SFRP1 in NPC cells was examined using bisulfate pyrosequencing; the Wnt/beta-catenin signaling pathway genes were studied using Western blotting. Compared with patients with high SFRP1 expression, patients with low SFRP1 expression had worse overall survival [HR, 2.32; 95% confidence interval (CI), 1.36-3.94; P = 0.002], disease-free survival (HR, 1.98; 95% CI, 1.23-3.18; P = 0.005), and distant metastasis-free survival (HR, 2.07; 95% CI, 1.19-3.59; P = 0.009). Multivariate Cox regression analysis indicated that SFRP1 was an independent prognostic factor. Furthermore, SFRP1 was significantly downregulated in NPC cell lines. SFRP1 overexpression suppressed NPC cell proliferation, migration, and invasion in vitro and lung colonization in vivo. SFRP1 expression was restored after treatment with a demethylation agent, and the SFRP1 promoter region was hypermethylated in NPC cells. beta-Catenin, c Myc, and cyclin D1 were downregulated after SFRP1 restoration, which suggested that SFRP1 suppressed growth and metastasis by inhibiting the Wnt/beta-catenin signaling pathway in NPC. SFRP1 provides further insight into NPC progression and may provide novel therapeutic targets for NPC treatment. PMID- 26276747 TI - ERbeta expression and breast cancer risk prediction for women with atypias. AB - Estrogen receptor (ER) beta is highly expressed in normal breast epithelium and a putative tumor suppressor. Atypical hyperplasia substantially increases breast cancer risk, but identification of biomarkers to further improve risk stratification is needed. We evaluated ERbeta expression in breast tissues from women with atypical hyperplasia and association with subsequent breast cancer risk. ERbeta expression was examined by immunohistochemistry in a well characterized 171-women cohort with atypical hyperplasia diagnosed 1967-1991. Nuclear ERbeta percent and intensity was scored in the atypia and adjacent normal lobules. An ERbeta sum score (percent + intensity) was calculated and grouped as low, moderate, or high. Competing risks regression was used to assess associations of ERbeta expression with breast cancer risk. After 15-year median follow-up, 36 women developed breast cancer. ERbeta expression was lower in atypia lobules in than normal lobules, by percent staining and intensity (both P < 0.001). Higher ERbeta expression in the atypia or normal lobules, evaluated by percent staining, intensity or sum score, decreased the risk of subsequent breast cancer by 2-fold (P = 0.04) and 2.5-fold (P = 0.006). High normal lobule ERbeta expression conferred the strongest protective effect in premenopausal women: the 20-year cumulative incidence of breast cancer was 0% for women younger than 45 years with high versus 31% for low-moderate ERbeta expression (P = 0.0008). High ERbeta expression was associated with a significantly decreased risk of breast cancer in women with atypical hyperplasia. These data suggest that ERbeta may be a useful biomarker for risk stratification and a novel therapeutic target for breast cancer risk reduction. PMID- 26276748 TI - Noninvasive molecular screening for oral precancer in Fanconi anemia patients. AB - LOH at chromosome arms 3p, 9p, 11q, and 17p are well-established oncogenetic aberrations in oral precancerous lesions and promising biomarkers to monitor the development of oral cancer. Noninvasive LOH screening of brushed oral cells is a preferable method for precancer detection in patients at increased risk for head and neck squamous cell carcinoma (HNSCC), such as patients with Fanconi anemia. We determined the prevalence of LOH in brushed samples of the oral epithelium of 141 patients with Fanconi anemia and 144 aged subjects, and studied the association between LOH and HNSCC. LOH was present in 14 (9.9%) nontransplanted patients with Fanconi anemia, whereas LOH was not detected in a low-risk group (n = 50, >58 years, nonsmoking/nonalcohol history) and a group with somewhat increased HNSCC risk (n = 94, >58 years, heavy smoking/excessive alcohol use); Fisher exact test, P = 0.023 and P = 0.001, respectively. Most frequent genetic alteration was LOH at 9p. Age was a significant predictor of LOH (OR, 1.13, P = 0.001). Five patients with Fanconi anemia developed HNSCC during the study at a median age of 39.6 years (range, 24.8-53.7). LOH was significantly associated with HNSCC (Fisher exact test, P = 0.000). Unexpectedly, the LOH assay could not be used for transplanted patients with Fanconi anemia because donor DNA in brushed oral epithelium, most likely from donor leukocytes present in the oral cavity, disturbed the analysis. Noninvasive screening using a LOH assay on brushed samples of the oral epithelium has a promising outlook in patients with Fanconi anemia. However, assays need to be adapted in case of stem cell transplantation, because of contaminating donor DNA. PMID- 26276749 TI - Isoflavone pharmacokinetics and metabolism after consumption of a standardized soy and soy-almond bread in men with asymptomatic prostate cancer. AB - Epidemiologic associations suggest that populations consuming substantial amounts of dietary soy exhibit a lower risk of prostate cancer. A 20-week randomized, phase II, crossover trial was conducted in 32 men with asymptomatic prostate cancer. The crossover involved 8 weeks each of soy bread (SB) and soy-almond bread (SAB). The primary objective was to investigate isoflavone bioavailability and metabolite profile. Secondary objectives include safety, compliance, and assessment of biomarkers linked to prostate carcinogenesis. Two distinct SBs were formulated to deliver approximately 60 mg aglycone equivalents of isoflavones per day. The isoflavones were present as aglycones (~78% as aglycones) in the SAB whereas in the standard SB predominantly as glucosides (18% total isoflavones as aglycones). Compliance to SB (97% +/- 4%) and SAB (92% +/- 18%) was excellent; toxicity was rare and limited to grade 1 gastrointestinal complaints. Pharmacokinetic studies between SB and SAB showed modest differences. Peak serum concentration time (Tmax) was significantly faster with SAB meal compared with SB in some isoflavonoids, and AUC0 to 24 h of dihydrodaidzein and O desmethylangolensin was significantly greater after an SB meal. An exploratory cluster analysis was used to identify four isoflavone-metabolizing phenotypes. Insulin-like growth factor-binding protein increased significantly by 41% (P = 0.024) with soy intervention. Findings from this study provide the necessary framework to study isoflavone-metabolizing phenotypes as a strategy for identification of individuals that might benefit or show resistance to cancer preventive strategies using dietary soy. A standardized SB used for future large scale randomized clinical trials to affect human prostate carcinogenesis is feasible. PMID- 26276750 TI - Double-Blind Randomized 12-Month Soy Intervention Had No Effects on Breast MRI Fibroglandular Tissue Density or Mammographic Density. AB - Soy supplementation by patients with breast cancer remains controversial. No controlled intervention studies have investigated the effects of soy supplementation on mammographic density in patients with breast cancer. We conducted a double-blind, randomized, placebo-controlled intervention study in previously treated patients with breast cancer (n = 66) and high-risk women (n = 29). We obtained digital mammograms and breast MRI scans at baseline and after 12 months of daily soy (50 mg isoflavones per day; n = 46) or placebo (n = 49) tablet supplementation. The total breast area (MA) and the area of mammographic density (MD) on the mammogram were measured using a validated computer-assisted method, and mammographic density percent (MD% = 100 * MD/MA) was determined. A well-tested computer algorithm was used to quantitatively measure the total breast volume (TBV) and fibroglandular tissue volume (FGV) on the breast MRI, and the FGV percent (FGV% = 100 * FGV/TBV) was calculated. On the basis of plasma soy isoflavone levels, compliance was excellent. Small decreases in MD% measured by the ratios of month 12 to baseline levels were seen in the soy (0.95) and the placebo (0.87) groups; these changes did not differ between the treatments (P = 0.38). Small decreases in FGV% were also found in both the soy (0.90) and the placebo (0.92) groups; these changes also did not differ between the treatments (P = 0.48). Results were comparable in patients with breast cancer and high-risk women. We found no evidence that soy supplementation would decrease mammographic density and that MRI might be more sensitive to changes in density than mammography. PMID- 26276751 TI - Consumption of soy isoflavone enriched bread in men with prostate cancer is associated with reduced proinflammatory cytokines and immunosuppressive cells. AB - We hypothesized that soy phytochemicals may have immunomodulatory properties that may affect prostate carcinogenesis and progression. A randomized, phase II trial was conducted in 32 patients with prostate cancer with asymptomatic biochemical recurrence but no measurable disease on standard staging studies. Patients were randomized to two slices of soy bread (34 mg isoflavones/slice) or soy bread containing almond powder daily as a source of beta-glucosidase. Flow cytometry and bioplex assays were used to measure cytokines or immune cell phenotype in blood at baseline (day 0) and following intervention (day 56). Adequate blood samples were available at enrollment and day 56 and evaluated. Multiple plasma cytokines and chemokines were significantly decreased on day 56 versus baseline. Subgroup analysis indicated reduced TH1 (P = 0.028) and myeloid-derived suppressor cell (MDSC)-associated cytokines (P = 0.035). TH2 and TH17 cytokines were not significantly altered. Phenotypic analysis revealed no change in CD8(+) or CD4(+) T cells but showed increased CD56(+) natural killer (NK) cells (P = 0.038). The percentage of cells with a T regulatory cell phenotype (CD4(+)CD25(+)FoxP3(+)) was significantly decreased after 56 days of soy bread (P = 0.0136). Significantly decreased monocytic (CD33(+)HLADR(neg)CD14(+)) MDSC were observed in patients consuming soy bread (P = 0.0056). These data suggest that soy bread modulates systemic soluble and cellular biomarkers consistent with limiting inflammation and suppression of MDSCs. Additional studies to elucidate impact on the carcinogenic process or as a complement to immune-based therapy are required. PMID- 26276752 TI - Colon Tumors with the Simultaneous Induction of Driver Mutations in APC, KRAS, and PIK3CA Still Progress through the Adenoma-to-carcinoma Sequence. AB - Human colorectal cancers often possess multiple mutations, including three to six driver mutations per tumor. The timing of when these mutations occur during tumor development and progression continues to be debated. More advanced lesions carry a greater number of driver mutations, indicating that colon tumors might progress from adenomas to carcinomas through the stepwise accumulation of mutations following tumor initiation. However, mutations that have been implicated in tumor progression have been identified in normal-appearing epithelial cells of the colon, leaving the possibility that these mutations might be present before the initiation of tumorigenesis. We utilized mouse models of colon cancer to investigate whether tumorigenesis still occurs through the adenoma-to-carcinoma sequence when multiple mutations are present at the time of tumor initiation. To create a model in which tumors could concomitantly possess mutations in Apc, Kras, and Pik3ca, we developed a novel minimally invasive technique to administer an adenovirus expressing Cre recombinase to a focal region of the colon. Here, we demonstrate that the presence of these additional driver mutations at the time of tumor initiation results in increased tumor multiplicity and an increased rate of progression to invasive adenocarcinomas. These cancers can even metastasize to retroperitoneal lymph nodes or the liver. However, despite having as many as three concomitant driver mutations at the time of initiation, these tumors still proceed through the adenoma-to-carcinoma sequence. PMID- 26276753 TI - Physical Activity and Prostate Tumor Vessel Morphology: Data from the Health Professionals Follow-up Study. AB - Vigorous activity is associated with lower risk of prostate cancer progression, but the biologic mechanisms are unknown. Exercise affects vascularization of tumors in animal models, and small, irregularly shaped vessels in prostate tumors are associated with fatal prostate cancer. We hypothesized that men who engaged in vigorous activity or brisk walking would have larger, more regularly shaped vessels in their prostate tumors. We prospectively examined whether physical activity was associated with prostate tumor microvessel morphology among 571 men in the Health Professionals Follow-up Study using ordinal logistic regression. Vessel size (MUm(2)), vessel lumen regularity (perimeter(2)/4 . Pi . area), and microvessel density (number/high-powered field) were ascertained in tumor sections stained for endothelial cell marker CD34. Vigorous activity [metabolic equivalent task (MET) >= 6], nonvigorous activity (MET < 6), and walking pace were assessed a median of 14 months before diagnosis. Prostate tumors from men who reported a brisk walking pace (3+ mph) had larger, more regularly shaped blood vessels compared with those of men who walked at a less than brisk pace [vessel regularity OR, 1.59; 95% confidence interval (CI), 1.11-2.27; P value, 0.01; vessel size OR, 1.48; 95% CI, 1.04-2.12; P value, 0.03]. Brisk walking was not associated with microvessel density; total vigorous and nonvigorous activities were not associated with vessel size, shape, or number. Brisk walking may be associated with larger, more regularly shaped vessels in prostate tumors. Additional research elucidating the effect of physical activity on prostate tumor biology is needed. PMID- 26276754 TI - Effect of Metformin on Breast Ductal Carcinoma In Situ Proliferation in a Randomized Presurgical Trial. AB - Metformin is associated with lower breast cancer risk in epidemiologic studies and showed decreased proliferation in HER2-positive breast cancer in a presurgical trial. To provide insight into its preventive potential, we measured proliferation by Ki-67 labeling index (LI) of intraepithelial lesions surrounding breast cancer. We randomly assigned 200 nondiabetic patients diagnosed with invasive breast cancer in core biopsies to metformin, 1,700 mg or placebo once daily for 28 days before surgery. Upon surgery, five to seven specimens of cancer adjacent (<=1 cm) and distant (>1 cm) tissue were screened for LCIS, ductal carcinoma in situ (DCIS), and ductal hyperplasia (DH). The prevalence of LCIS, DCIS, and DH was 4.5% (9/200), 67% (133/200), and 35% (69/200), respectively. Overall, metformin did not affect Ki-67 LI in premalignant disorders. The median posttreatment Ki-67 LI (IQR) in the metformin and placebo arm was, respectively, 15% (5-15) versus 5% (4-6) in LCIS (P = 0.1), 12% (8-20) versus 10% (7-24) in DCIS (P = 0.9), and 3% (1-4) versus 3% (1-4) in DH (P = 0.5). However, posttreatment Ki-67 in HER2-positive DCIS lesions was significantly lower in women randomized to metformin especially when ER was coexpressed: 22% (11-32) versus 35% (30-40) in HER2-positive DCIS (n = 22, P = .06); 12% (7-18) versus 32% (27-42) in ER-positive/HER2-positive DCIS (n = 15, P = .004). Eight of 22 (36%) HER2-positive DCIS were adjacent to HER2-negative invasive breast cancer. In tissue samples obtained following 4 weeks of study drug, proliferation was lower in HER2-positive DCIS for women randomized to metformin versus placebo. An adjuvant trial incorporating metformin in HER2-positive DCIS is warranted. PMID- 26276755 TI - Occupational lung disease survey of respiratory physicians in Northern Ireland. AB - BACKGROUND: Respiratory physicians are likely to encounter occupational lung disease (OLD) in their daily practice. AIMS: To assess the profile of cases being encountered by general respiratory physicians in Northern Ireland (NI) and determine satisfaction with training, confidence in diagnosis and management of OLD. METHODS: An online survey of all consultant respiratory physicians currently practising in NI. Questions assessed the numbers of new cases seen over the preceding year, case type, satisfaction with specialist registrar training in OLD and degree of confidence in the diagnosis and management of these conditions. RESULTS: Of the 40 consultants identified, the response rate was 80% (n = 32) with 94% of respondents (n = 30) indicating they had dealt with patients suspected of having occupation-related respiratory symptoms. The most commonly encountered OLDs were pleural plaques (91% of respondents), occupational asthma (88%), asbestosis (84%), non-asbestosis pulmonary fibrosis (76%), hypersensitivity pneumonitis (67%) and mesothelioma (66%). Just over one third of consultants (36%, n = 10) indicated a lack of confidence in diagnosis and management of OLD with almost half (48%) dissatisfied with OLD training as a registrar and a further 78% (n = 25) indicating they would value additional training in OLD as a consultant. CONCLUSIONS: The majority of respiratory consultants in NI encountered OLD in their day to day practice and half were dissatisfied with their specialist registrar training in OLD and express a lack of confidence in the diagnosis and management of these conditions. This highlights the need for additional training at both registrar and consultant level. PMID- 26276756 TI - Impact of rail medical standard on obstructive sleep apnoea prevalence. AB - BACKGROUND: The 2004 edition of the National Standard for Health Assessment of Rail Safety Workers (the standard) used the Epworth Sleepiness Scale (ESS) to screen for excessive daytime sleepiness related to obstructive sleep apnoea (OSA). The 2012 edition of the standard expanded the OSA screening matrix to include body mass index, comorbid hypertension and type 2 diabetes as triggers requiring a sleep study to be undertaken irrespective of the ESS. AIMS: To assess the impact of the new standard on the estimated prevalence of OSA in railway workers. METHODS: An analysis of data on safety critical employees referred for rail safety health assessment during the 2013 calendar year and meeting the criteria for sleep study referral. Sleep study outcomes were used to assess the predictive value of screening under the new standard. RESULTS: A total of 200/4311 workers were investigated with a sleep study. One hundred and ninety three met the new risk factor criteria and 182 (91%) were newly diagnosed with OSA. The prevalence of OSA in the study population was 7%, compared with 2% in 2009. No worker reported an elevated ESS. The false positive to true positive ratio was 0.1 (95% CI 0.06-0.16). CONCLUSIONS: The new medical standard has resulted in an increased estimate of the prevalence of OSA in rail workers. This study supports the use of objective clinical risk factors to select workers for further investigation, aiming to minimize the risk of accidents associated with excessive daytime sleepiness and other comorbid conditions of OSA. PMID- 26276757 TI - Accreditation of occupational health services in Norway. AB - BACKGROUND: In 2010, an accreditation system for occupational health services (OHS) in Norway was implemented. AIMS: To examine OHS experiences of the accreditation system in Norway 4 years after its implementation. METHODS: A web based questionnaire was sent to all accredited OHS asking about their experiences with the accreditation system. Responses were compared with a similar survey conducted in 2011. RESULTS: The response rate was 76% (173/228). OHS reported that the most common changes they had had to make to achieve accreditation were: improvement of their quality assurance system (53%), a plan for competence development (44%) and increased staffing in occupational hygiene (36%) and occupational medicine (28%). The OHS attributed improved quality in their own OHS (56%) and in OHS in Norway (47%), to the accreditation process. CONCLUSIONS: The accreditation system was well accepted by OHS, who reported that it had improved the quality of their OHS and of OHS in Norway. The results are similar to the findings of a 2011 survey. PMID- 26276758 TI - Health care workers' influenza vaccination: motivations and mandatory mask policy. AB - BACKGROUND: Vaccination of health care workers (HCW) against seasonal influenza (SI) is recommended but vaccination rate rarely reach >30%. Vaccination coverage against 2009 pandemic influenza (PI) was 52% in our hospital, whilst a new policy requiring unvaccinated HCW to wear a mask during patient care duties was enforced. AIMS: To investigate the determinants of this higher vaccination acceptance for PI and to look for an association with the new mask-wearing policy. METHODS: A retrospective cohort study, involving HCW of three critical departments of a 1023-bed, tertiary-care university hospital in Switzerland. Self reported 2009-10 SI and 2009 PI vaccination statuses, reasons and demographic data were collected through a literature-based questionnaire. Descriptive statistics, uni- and multivariate analyses were then performed. RESULTS: There were 472 respondents with a response rate of 54%. Self-reported vaccination acceptance was 64% for PI and 53% for SI. PI vaccination acceptance was associated with being vaccinated against SI (OR 9.5; 95% CI 5.5-16.4), being a physician (OR 7.7; 95% CI 3.1-19.1) and feeling uncomfortable wearing a mask (OR 1.7; 95% CI 1.0-2.8). Main motives for refusing vaccination were: preference for wearing a surgical mask (80% for PI, not applicable for SI) and concerns about vaccine safety (64%, 50%) and efficacy (44%, 35%). CONCLUSIONS: The new mask wearing policy was a motivation for vaccination but also offered an alternative to non-compliant HCW. Concerns about vaccine safety and efficiency and self interest of health care workers are still main determinants for influenza vaccination acceptance. Better incentives are needed to encourage vaccination amongst non-physician HCW. PMID- 26276759 TI - Mundane science use in a practice theoretical perspective: Different understandings of the relations between citizen-consumers and public communication initiatives build on scientific claims. AB - Public communication initiatives play a part in placing complicated scientific claims in citizen-consumers' everyday contexts. Lay reactions to scientific claims framed in public communication, and attempts to engage citizens, have been important subjects of discussion in the literatures of public understanding and public engagement with science. Many of the public communication initiatives, however, address lay people as consumers rather than citizens. This creates specific challenges for understanding public engagement with science and scientific citizenship. The article compares five different understandings of the relations between citizen-consumers and public issue communication involving science, where the first four types are widely represented in the Public Understanding of Science discussions. The fifth understanding is a practice theoretical perspective. The article suggests how the public understanding of and engagement in science literature can benefit from including a practice theoretical approach to research about mundane science use and public engagement. PMID- 26276760 TI - Pharmacists could work in GP premises under proposed new model of care. PMID- 26276761 TI - Prognostic signature of protocadherin 10 methylation in curatively resected pathological stage I non-small-cell lung cancer. AB - Although curative resection is the current treatment of choice for localized non small-cell lung cancer (NSCLC), patients show a wide spectrum of survival even after complete resection of pathological stage I NSCLC. Thus, identifying molecular biomarkers that help to accurately select patients at high risk of relapse is an important key to improving the treatment strategy. The purpose of this study was to evaluate the prognostic signature of protocadherin 10 (PCDH10) promoter methylation in curatively resected pathological stage I NSCLC. Using methylation-specific polymerase chain reaction assays, methylation of PCDH10 promoter was assessed in cancer tissues of 109 patients who underwent curative resection of pathological stage I NSCLC. Associations between PCDH10 methylation status and disease outcome was analyzed. PCDH10 promoter methylation was detected in 46/109 patients (42.2%). Patients with methylated PCDH10 showed significantly worse recurrence-free, overall, and disease-specific survival compared with those without methylation (P < 0.0001, P = 0.0004, P = 0.0002, respectively). Multivariate Cox proportional hazard regression analysis revealed that adjusted hazard ratios of methylated PCDH10 were 5.159 for recurrence-free, 1.817 for overall, and 5.478 for disease-specific survival (P = 0.0005, P = 0.1475, P = 0.0109, respectively). The pattern of recurrence was not significantly different between patients with and without PCDH10 methylation (P = 0.5074). PCDH10 methylation is a potential biomarker that predicts a poor prognosis after curative resection of pathological stage I NSCLC. Assessment of PCDH10 methylation status might assist in patient stratification for determining an appropriate adjuvant treatment and follow-up strategy. PMID- 26276762 TI - Prevalence of Complementary and Alternative Medicine Usage in Vietnamese American Asthmatic Children. AB - This study examined the frequency and type of complementary and alternative medicine (CAM) therapy, as well as characteristics associated with CAM usage. A survey about parental preferences and beliefs regarding CAM usage was distributed to 5 schools with predominantly low socioeconomic Vietnamese children. For the 360 Vietnamese children previously diagnosed with asthma whose families responded, most preferred conventional therapy as prescribed by the physician. The prevalence of CAM usage was 38.1%. Common CAM therapies were steam inhalation, creams/topical oils, foods, prayer, oil inhalation, massage, herbal medication, coining, and cupping. Significant predictors of CAM usage were older age (11-12 years) (P = .038), English language of survey response (P = .001), environmental tobacco smoke exposure (P = .001), fear of long-term medication usage, and perception of asthma as a condition related to genetics (P = .023). These findings suggest that assessing CAM therapy will provide a more holistic approach to asthma therapy. PMID- 26276763 TI - The global health network on alcohol control: successes and limits of evidence based advocacy. AB - Global efforts to address alcohol harm have significantly increased since the mid 1990 s. By 2010, the World Health Organization (WHO) had adopted the non-binding Global Strategy to Reduce the Harmful Use of Alcohol. This study investigates the role of a global health network, anchored by the Global Alcohol Policy Alliance (GAPA), which has used scientific evidence on harm and effective interventions to advocate for greater global public health efforts to reduce alcohol harm. The study uses process-tracing methodology and expert interviews to evaluate the accomplishments and limitations of this network. The study documents how network members have not only contributed to greater global awareness about alcohol harm, but also advanced a public health approach to addressing this issue at the global level. Although the current network represents an expanding global coalition of like-minded individuals, it faces considerable challenges in advancing its cause towards successful implementation of effective alcohol control policies across many low- and middle-income countries (LMICs). The analysis reveals a need to transform the network into a formal coalition of regional and national organizations that represent a broader variety of constituents, including the medical community, consumer groups and development-focused non-governmental organizations. Considering the growing harm of alcohol abuse in LMICs and the availability of proven and cost-effective public health interventions, alcohol control represents an excellent 'buy' for donors interested in addressing non communicable diseases. Alcohol control has broad beneficial effects for human development, including promoting road safety and reducing domestic violence and health care costs across a wide variety of illnesses caused by alcohol consumption. PMID- 26276764 TI - Exploiting Atropisomerism to Increase the Target Selectivity of Kinase Inhibitors. AB - Many biologically active molecules exist as rapidly interconverting atropisomeric mixtures. Whereas one atropisomer inhibits the desired target, the other can lead to off-target effects. Herein, we study atropisomerism as a possibility to improve the selectivities of kinase inhibitors through the synthesis of conformationally stable pyrrolopyrimidines. Each atropisomer was isolated by HPLC on a chiral stationary phase and subjected to inhibitor profiling across a panel of 18 tyrosine kinases. Notably different selectivity patterns between atropisomers were observed, as well as improved selectivity compared to a rapidly interconverting parent molecule. Computational docking studies then provided insights into the structure-based origins of these effects. This study is one of the first examples of the intentional preorganization of a promiscuous scaffold along an atropisomeric axis to increase target selectivity, and provides fundamental insights that may be applied to other atropisomeric target scaffolds. PMID- 26276765 TI - Integrated Microfluidics for Protein Modification Discovery. AB - Protein post-translational modifications mediate dynamic cellular processes with broad implications in human disease pathogenesis. There is a large demand for high-throughput technologies supporting post-translational modifications research, and both mass spectrometry and protein arrays have been successfully utilized for this purpose. Protein arrays override the major limitation of target protein abundance inherently associated with MS analysis. This technology, however, is typically restricted to pre-purified proteins spotted in a fixed composition on chips with limited life-time and functionality. In addition, the chips are expensive and designed for a single use, making complex experiments cost-prohibitive. Combining microfluidics with in situ protein expression from a cDNA microarray addressed these limitations. Based on this approach, we introduce a modular integrated microfluidic platform for multiple post-translational modifications analysis of freshly synthesized protein arrays (IMPA). The system's potency, specificity and flexibility are demonstrated for tyrosine phosphorylation and ubiquitination in quasicellular environments. Unlimited by design and protein composition, and relying on minute amounts of biological material and cost-effective technology, this unique approach is applicable for a broad range of basic, biomedical and biomarker research. PMID- 26276766 TI - Laboratory medicine and value-based health care. PMID- 26276767 TI - The persistence of misinformation. PMID- 26276768 TI - Acute leukemias of ambiguous origin. AB - OBJECTIVES: This session of the Society for Hematopathology/European Association for Haematopathology Workshop focused on acute leukemias of ambiguous origin. METHODS: We provide an overview of mixed-phenotype acute leukemia (MPAL) as recognized in the current World Health Organization classification and summarize diagnostic criteria for major categories of MPAL: B/myeloid, T/myeloid, B/T, and B/T/myeloid. RESULTS: Most MPAL cases submitted were B/myeloid and T/myeloid MPAL, the most frequent types, but three cases of B/T MPAL were also submitted, and examples of all categories are illustrated. We emphasize that a comprehensive approach to immunophenotyping is required to accurately establish the diagnosis of MPAL. Flow cytometry immunophenotyping using a large panel of antibodies is needed as well as confirmatory immunohistochemical analysis and cytochemistry studies for myeloperoxidase and nonspecific esterase. We discuss technical issues in determining blast lineage and possible pitfalls in MPAL diagnosis. In particular, rare cases of B-acute lymphoblastic leukemia (B-ALL) can express myeloperoxidase but are otherwise consistent with B-ALL and should be treated as such. Last, we review the differential diagnosis between acute undifferentiated leukemia and acute myeloid leukemia with minimal differentiation. CONCLUSIONS: There was an agreement that diagnosis of MPAL can be challenging, especially if applied flow cytometry panels are not comprehensive enough. PMID- 26276769 TI - Hematolymphoid neoplasms associated with rearrangements of PDGFRA, PDGFRB, and FGFR1. AB - OBJECTIVES: This session of the 2013 Society for Hematopathology/European Association for Haematopathology Workshop was dedicated to tumors currently included in the World Health Organization (WHO) classification category of myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, and FGFR1. METHODS: We use the cases submitted to this session to review the clinicopathologic and genetic spectrum of these neoplasms, methods for their diagnosis, and issues related to the WHO classification terminology. Since many patients with these neoplasms have eosinophilia, we also briefly mention other causes of clonal eosinophilia. RESULTS: These neoplasms are the result of gene fusions involving any one of these three tyrosine kinase genes. A variety of gene fusion partners have been found consistently for each category of neoplasms. Diagnoses of these neoplasms are often highly challenging and require a high index of suspicion and a multidisciplinary approach. CONCLUSIONS: Early recognition of these neoplasms is important because patients with neoplasms associated with PDGFRA or PDGFRB fusions often respond to tyrosine kinase inhibitor therapy, whereas patients with neoplasms associated with FGFR1 fusions usually do not respond. PMID- 26276770 TI - B-acute lymphoblastic leukemia/lymphoblastic lymphoma. AB - OBJECTIVES: This session of the 2013 Society of Hematopathology/European Association for Haematopathology Workshop was dedicated to B-acute lymphoblastic leukemia (B-ALL)/lymphoblastic lymphoma (LBL) with recurrent translocations and not otherwise specified. METHODS: In this review, we summarize the cases discussed during the workshop, review the pertinent and most recent literature on the respective topics, and provide a few key points that may aid in the workup of patients with B-ALL/LBL. RESULTS: Many of the submitted cases showed interesting diagnostic, immunophenotypic, or clinical aspects of B-ALL with BCR/ABL1, MLL associated, and other recurrent chromosomal abnormalities. Several cases showed rare aberrancies such as coexistent IGH/BCL2 and MYC rearrangements and raised issues in classification. Other cases had unusual clinical presentations, including B-ALL with hypereosinophilia and therapy-related B-ALL. Several cases highlighted the role of flow cytometry immunophenotyping in distinguishing benign B-cell precursors from aberrant lymphoblasts, and other cases raised questions regarding the clinical importance of myeloperoxidase positivity in acute lymphoblastic leukemia. CONCLUSIONS: The complexity and spectrum of cases presented in this review highlight the importance of clinicopathologic correlation and the value of ancillary studies in the classification and workup of patients with B-ALL/LBL. PMID- 26276771 TI - T-lymphoblastic leukemia/lymphoma. AB - OBJECTIVES: To review important concepts from the 2013 Society for Hematopathology/European Association for Haematopathology Workshop session on T acute lymphoblastic leukemia/T-lymphoblastic lymphoma (T-ALL/T-LBL). METHODS: Twenty-one submitted cases are reviewed and summarized, with emphasis on key diagnostic or biologic points, and supplemented with relevant literature citations. RESULTS: Early T-cell precursor (ETP)-ALL represented about one-third of all cases submitted. It is important to recognize ETP-ALL, because these patients have a poor prognosis if treated with standard therapy. A consensus immunophenotype has been developed to aid in the recognition of these cases. Other cases submitted illustrated rare entities, including two cases of Philadelphia chromosome-positive T-ALL, two cases of T-ALL associated with MYC translocations, and single cases illustrating various diseases. A subset of cases submitted illustrated issues related to differential diagnosis of T-ALL/T-LBL. CONCLUSIONS: In view of the growing importance of molecular genetic analysis in the diagnosis and prognosis of T-ALL/T-LBL, it is important for pathologists to keep abreast of these developments. Currently, routine histopathology, immunophenotyping, conventional cytogenetic analysis, fluorescence in situ hybridization, and clonality testing are usually adequate to establish the diagnosis. However, as therapies become more targeted, assessment for relevant genetic abnormalities, either through candidate gene or broad-scale unbiased approaches, may become necessary. PMID- 26276772 TI - Limiting the testing of AST: a diagnostically nonspecific enzyme. AB - OBJECTIVES: Annually, millions of pairs of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) tests are ordered. These enzymes are highly correlated, and ALT is far more specific diagnostically than AST. To reduce AST testing, we suggest measuring AST only when ALT exceeds a predetermined limit. METHODS: We derived the proportions of elevated ASTs that would not be measured based on 15 months of paired inpatient and outpatient ALT and AST data. RESULTS: For inpatients, a 35 U/L ALT limit for initiating AST testing would reduce AST testing by 51%, missing only 3% and 7.5% of ASTs exceeding 50 U/L and 35 U/L, respectively. In outpatients, AST testing can be reduced by more than 65%, with fewer missed elevated ASTs (0.5% and 2% of the ASTs exceeding 50 U/L and 35 U/L, respectively). CONCLUSIONS: Conservatively, $100 million could be saved annually in the US health care budget by selectively limiting AST testing in just the US outpatient environment. PMID- 26276773 TI - Calciphylaxis and the persistence of medical misinformation in the era of Google. AB - OBJECTIVES: We illustrate the important and troubling issue of persistent misinformation and false claims in the medical literature using a frequently cited case inaccurately believed by many to be the first case of calciphylaxis. METHODS: We identified a recurring error in the medical literature in the form of numerous citations of a study from the 1890s of a 6-month-old child with idiopathic infantile arterial calcification that is purported to be the first description of a case of calciphylaxis. We performed searches to determine the frequency of this error. Google Scholar and PubMed were searched for references citing the Bryant and White article. Accuracy of the citations was determined. RESULTS: A Google Scholar search identified 33 references that incorrectly cite the Bryant and White article as the first description of a case of calciphylaxis. Of the 100 most recent PubMed publications on calciphylaxis, we identified five studies that incorrectly attribute the Bryant and White article as the first description of calciphylaxis, which accounts for approximately 5% of the contemporary literature on this topic. CONCLUSIONS: Medical misinformation such as this is frequently perpetuated. We propose that computational resources could be better used to flag erroneous and contradicted claims to update and correct the literature. PMID- 26276774 TI - The American Society for Clinical Pathology's 2014 vacancy survey of medical laboratories in the United States. AB - OBJECTIVES: To determine the extent and distribution of workforce shortages within the nation's medical laboratories. Historically, the results of this biennial survey have served as a basis for additional research on laboratory recruitment, retention, education, marketing, certification, and advocacy. METHODS: The 2014 Vacancy Survey was conducted through collaboration between American Society for Clinical Pathology's Institute of Science, Technology, and Policy in Washington, DC, and the Evaluation, Measurement, and Assessment Department and Board of Certification in Chicago, Illinois. Data were collected via an Internet survey that was distributed to individuals who were able to report on staffing and certifications for their laboratories. RESULTS: Data reveal increased overall vacancy rates since 2012 for all departments surveyed except cytology and cytogenetics. Also, results show higher anticipated retirement rates for both staff and supervisors. Overall certification rates are highest among laboratory personnel in cytogenetics, hematology/coagulation, and flow cytometry departments and lowest among phlebotomy, specimen processing, and anatomic pathology. CONCLUSIONS: Factors such as retirement and the improving economy are driving the need for more laboratory professionals. Recruitment of qualified laboratory professionals in the workforce and students in laboratory programs will be the key in fulfilling the higher vacancies revealed from the survey results in 2014. PMID- 26276775 TI - Evaluating the utility of trefoil factor 1 as a mammary-specific immunostain compared and in conjunction with GATA-3 and mammaglobin in the distinction between carcinoma of breast and lung. AB - OBJECTIVES: The distinction between metastatic breast carcinomas (BCs) and primary lung carcinomas (PLCs) can be difficult. This study tested the utility of trefoil factor 1 (TFF1) for this purpose and compared it with mammaglobin and GATA protein binding 3 (GATA-3). METHODS: Tissue microarrays containing 365 BCs and 338 PLCs were stained with TFF1, mammaglobin, and GATA-3, and an H-score was calculated. Sensitivity, specificity, and accuracy were calculated, and logistical regression analysis was performed. RESULTS: Accuracy of correctly classifying the tumor type was 81.9%, 71.3%, and 64.0% for GATA-3, mammaglobin, and TFF1, respectively. Odds ratios for selecting BCs were 25.69, 93.15, and 4.17, respectively, with P values less than .001. With a single exception, the best immunopanel included GATA-3 and mammaglobin in all comparisons. CONCLUSIONS: TFF1 demonstrated breast specificity but was inferior to mammaglobin and GATA-3. Therefore, its routine clinical use may not be justified. TFF1 showed little benefit when added to an immunopanel. PMID- 26276777 TI - Probabilistic issues with sentinel lymph nodes in malignant melanoma. AB - OBJECTIVES: To address issues of probability for sentinel lymph node results in melanoma and provide details about the probabilistic nature of the numbers of sentinel nodes as well as to address how these issues relate to tumor thickness and patient outcomes. METHODS: Analysis of the probability of observing sentinel node metastases uses the discrete exponential probability distribution to address the number of observed positive sentinel nodes. In addition, mathematical functions derived from survival analysis are used. Data are then chosen from the literature to illustrate the approach and to derive results. RESULTS: Observations about the numbers of positive and negative sentinel nodes closely follow discrete exponential probability distributions, and the relationship between the probability of a positive sentinel node and tumor thickness follows closely a function derived from survival analysis. Sentinel node results relate to tumor thickness as well as to the total number of nodes harvested but fall short of identifying all those who eventually develop metastatic melanoma. CONCLUSIONS: Probability analyses provide useful insight into the success and failure of the sentinel node biopsy procedure in patients with melanoma. PMID- 26276776 TI - Distinct beta-catenin and PIK3CA mutation profiles in endometriosis-associated ovarian endometrioid and clear cell carcinomas. AB - OBJECTIVES: We focused on the differences in molecular mechanisms in the early stages of endometriosis-associated ovarian endometrioid carcinoma (OEMCa) and ovarian clear cell carcinoma (OCCCa). METHODS: Alterations in the beta-catenin and PIK3CA genes, as well as expression of their associated markers, were investigated. RESULTS: Mutations in exon 3 of the beta-catenin gene were identified in 21 (60%) of 35 OEMCas. The mutations were also detected in the coexisting nonatypical (52.4%) and atypical (73.3%) endometriosis, and the single nucleotide substitutions were identical in most cases. In contrast, the mutations were not identified in any of the OCCCas and their coexisting endometriosis. PIK3CA mutations were observed in 11 (31.4%) of 35 OEMCas and 10 (35.7%) of 28 OCCCas. Ten of 11 OEMCas had PIK3CA mutations in exon 9, and eight of 10 OCCCas had them in exon 20. The same mutations were also detected in the coexisting nonatypical and/or atypical endometriosis in three OEMCas and four OCCCas. In addition, significant differences in the expression of pAkt, hepatocyte nuclear factor 1beta, hypoxia-inducible factor 1alpha, p65, and inducible nitric oxide synthase were evident between the two types of tumors and their coexisting endometriosis. CONCLUSIONS: Distinct molecular events may occur in relatively early stages of tumorigenesis of endometriosis-associated OEMCas and OCCCas. PMID- 26276778 TI - Human papillomavirus oncogenic mRNA testing for cervical cancer screening: baseline and longitudinal results from the CLEAR study. AB - OBJECTIVES: This study determined the longitudinal clinical performance of a high risk human papillomavirus (HR-HPV) E6/E7 RNA assay (Aptima HPV [AHPV]; Hologic, San Diego, CA) compared with an HR-HPV DNA assay (Hybrid Capture 2 [HC2]; Qiagen, Gaithersburg, MD) as an adjunctive method for cervical cancer screening. METHODS: Women 30 years or older with a negative result for intraepithelial lesions or malignancy cytology (n = 10,860) positive by AHPV and/or HC2 assays and randomly selected women negative by both assays were referred to colposcopy at baseline. Women without baseline cervical intraepithelial neoplasia (CIN) grade 2 or higher (CIN2+) continued into the 3-year follow-up. RESULTS: The specificity of AHPV for CIN2 or lower was significantly greater at 96.3% compared with HC2 specificity of 94.8% (P < .001). Estimated sensitivities and risks for detection of CIN2+ were similar between the two assays. After 3 years of follow-up, women negative by either human papillomavirus test had a very low risk of CIN2+ (<0.3%) compared with CIN2+ risk in women with positive AHPV results (6.3%) or positive HC2 results (5.1%). CONCLUSIONS: These results support the use of AHPV as a safe and effective adjunctive cervical cancer screening method. PMID- 26276779 TI - Complex measurements may be required to establish the prognostic impact of immunophenotypic markers in AML. AB - OBJECTIVES: The prognostic impact of immunophenotypic markers in acute myeloid leukemia (AML) is controversial. METHODS: We retrospectively analyzed the value of CD34, CD117, CD7, and CD123 expression in a consecutive series of 592 adult patients with de novo AML. RESULTS: CD34+ measured as a percentage (>=2.88%) and CD34 mean fluorescence intensity (MFI) (>=146.79, arbitrary units [AU]) expression had a prognostic impact in terms of overall survival (OS; P = .005, P = .003), leukemia-free survival (LFS; P = .011, P < .001), and cumulative incidence of relapse (CIR; P = .014, P =. 001). The percentage of CD117+ cells (61.29%) was associated with shorter LFS (P =. 043), and CD117 MFI (>=284.01 AU) was associated with a shorter OS (P =. 033) and LFS (P =. 028). In the multivariate analysis, high CD34 MFI retained the independent value as predictor of LFS and CIR (P =. 012; hazard ratio [HR], 1.59; 95% confidence interval [CI], 1.11-2.28 and P =. 045; HR, 1.58; 95% CI, 1.01-2.46). CONCLUSIONS: CD34 positivity threshold with prognostic relevance is low (3% positive cells). Immunophenotypic findings in AML probably could only be fully exploited after a complex analysis that takes into account unconventional thresholds and the MFI. PMID- 26276780 TI - Morphologically occult systemic mastocytosis in bone marrow: clinicopathologic features and an algorithmic approach to diagnosis. AB - OBJECTIVES: Bone marrow (BM) biopsy specimens involved by systemic mastocytosis (SM) typically show multifocal, compact, dense aggregates of spindled mast cells (MCs). However, some cases lack aggregate formation and fulfill the World Health Organization 2008 criteria for SM, based on minor criteria. METHODS: We identified 26 BM cases of KIT D816V-mutated, morphologically occult SM in the BM. RESULTS: All patients had some combination of allergic/MC activating symptoms. Peripheral blood counts were generally normal. BM aspirates showed 5% or less MCs, which were only occasionally spindled. BM biopsy specimens showed no morphologic classic MC lesions. Tryptase immunohistochemistry (IHC) demonstrated interstitial, individually distributed MCs (up to 5%) with prominent spindling, lacking aggregate formation. MCs coexpressed CD25 by IHC and/or flow cytometry. Spindled MCs constituted more than 25% of total MCs in all cases and more than 50% in 20 of 26 cases. CONCLUSIONS: Morphologically occult involvement of normal appearing BM by SM will be missed without appropriate clinical suspicion and pathologic evaluation by tryptase and CD25 IHC and KIT D816V mutation analysis. On the basis of these findings, we propose a cost-effective, data-driven, evidence-based algorithmic approach to the workup of these cases. PMID- 26276781 TI - Regressive change in high-grade ductal carcinoma in situ of the breast: histopathologic spectrum and biologic importance. AB - OBJECTIVES: High-grade ductal carcinoma in situ (HG-DCIS) of the breast often shows tumor attenuation and reactive fibrosis. These changes, previously described as "regressive," have been paradoxically associated with an increased risk of invasive carcinoma. We aimed to further characterize the spectrum of the so-called regressive changes (RCs) in HG-DCIS. METHODS: We reviewed 52 consecutive cases of HG-DCIS on biopsy specimens followed by excision. RCs were divided into early (stage 1) and advanced (stages 2 and 3) stages according to the degree of ductal fibrosis and tumor effacement. The presence of inflammation, hormone receptor status, and diagnosis on excision were recorded. RESULTS: RCs were seen in 51 (98%) cases: 96%, 76.4%, and 39.2% cases showed stages 1, 2, and 3, respectively. Periductal T cells with a normal CD4/CD8 ratio were constantly seen. Advanced RCs and inflammation were more frequent in estrogen and progesterone receptor-negative tumors. RCs were not associated with invasion but correlated with a larger residual HG-DCIS volume on excision. CONCLUSIONS: Regression in HG-DCIS is frequent. It may reflect a targeted immune response to certain phenotypes, mainly hormone receptor-negative lesions. Nonetheless, RCs do not lead to complete tumor obliteration but correlate with aggressive tumor characteristics instead. PMID- 26276782 TI - Polypoid laryngeal inflammatory myofibroblastic tumors: misleading lesions: description of six cases showing ALK overexpression. AB - OBJECTIVES: Laryngeal inflammatory myofibroblastic tumors (IMTs) are rarely reported in the literature but may be underrecognized. To better characterize their features, we report a series of six cases. METHODS: The clinicopathologic findings, including immunohistochemistry, fluorescence in situ hybridization (FISH) analysis, and follow-up, were evaluated and a review of the literature was performed. RESULTS: These cases presented as small polypoid vocal cord or ventricular band lesions, with a more advanced mean age at diagnosis (49 years) than typically reported in other localizations. Apart from one secondary revision surgery, no complementary treatment and no recurrences were observed. Histologically, various morphologic features were seen. All tumors were spindle cell proliferations on a myxoid background with more or less atypia and significant inflammatory infiltrate. All six cases showed anaplastic lymphoma kinase (ALK) immunohistochemical expression. FISH rearrangement was present in four of six cases. Only two cases were initially diagnosed as IMT. CONCLUSIONS: According to our series, laryngeal IMTs are easily misdiagnosed. They have a good prognosis, and ALK immunohistochemistry should be carried out to assess this diagnosis when spindle cell proliferations are observed in this localization. PMID- 26276783 TI - Computer-aided detection of rare tumor populations in flow cytometry: an example with classic Hodgkin lymphoma. AB - OBJECTIVES: Diagnosing classical Hodgkin lymphoma (cHL) by flow cytometry (FC) relies on an observer gating rare populations of Hodgkin/Reed Sternberg (HRS) cells. Here, we apply machine-learning methods to aid in the detection of rare tumor cell populations using data derived from clinical FC analysis of cHL as a model disease. METHODS: FC data from 144 clinical cases using a nine-color FC reagent panel were analyzed using Python 2.7 and the "scikit-learn" module. RESULTS: Seventy-eight 50 * 50 two-dimensional histograms were generated from routine FC data and a reciprocal power function applied to favor rare events. Data were classified by support vector machine (SVM), gradient boosting, and random forest classifiers. All three classifiers showed no statistical difference in performance, with 89%-92% accuracy on cross-validation. Nearly all classifiers misclassified the same set of cases, with more false-positive than false-negative cases. Dimensionality reduction by ensemble methods selected for data points in a CD5+/ CD40+/CD64- region. CONCLUSIONS: All classifiers provide probabilistic confidences for each result, and diagnostic cutoffs can be chosen to minimize false negatives and serve as a screening tool. Computational exclusion of manually gated HRS cells had little impact on the overall performance of selected support vectors in SVM or dimensionality reduction, suggesting that features of the immune response in cHL may dictate the method accuracy. We hypothesize there are distinct inflammatory cells that suggest cHL. PMID- 26276784 TI - Resident remediation: start from scratch. PMID- 26276785 TI - Reference intervals data mining: getting the right paper. PMID- 26276786 TI - Temozolomide for central nervous system involvement in mycosis fungoides. AB - BACKGROUND: The central nervous system (CNS) is one of the most commonly involved sites in the systemic progression of primary cutaneous T cell lymphomas (CTCLs) such as mycosis fungoides (MF). There is no consensus on the treatment of CNS progression in CTCL, but survival of 3-6 months is suggested when methotrexate based chemotherapy and/or CNS irradiation is used. Temozolomide is active in earlier stages of MF and readily crosses the blood-brain barrier. There are no published data on its use in MF patients with CNS involvement. METHODS: Four MF patients were treated with oral temozolomide (200 mg/m(2) per day for 5 d on a 28 day cycle) for CNS progression. Two patients received temozolomide with low-dose CNS irradiation as initial treatment, and two received temozolomide following disease progression after methotrexate-based chemotherapy and CNS irradiation. All patients received dexamethasone. RESULTS: Temozolomide was well tolerated; there were no treatment withdrawals or dose reductions caused by toxicity. Patient 1 had an excellent partial response in pre-irradiated disease. Patient 2 showed disease stabilization following irradiation. Patient 3 showed a complete response after a partial response to irradiation. Patient 4 demonstrated continued stabilization after a partial response to irradiation. Overall survival ranged from 10 to 33 months. Patient 3 remains alive and symptom-free at 23 months following treatment. CONCLUSIONS: Temozolomide following low-dose CNS irradiation appears to be well tolerated and effective in MF patients with CNS progression. It may represent a less toxic alternative to chemotherapy containing methotrexate or an option for second-line therapy. PMID- 26276787 TI - Idiopathic constipation in children clinical practice guidelines. PMID- 26276788 TI - Premature births are blamed for high death rate in UK's under 5s compared with Sweden. PMID- 26276789 TI - Ethical implications of HIV self-testing. AB - In April 2015, the first legally approved HIV self-testing kit went on sale in the UK-except Northern Ireland where they remain illegal. These tests allow individuals to test their HIV status and read the result in the privacy of their own home, much like a home pregnancy test. This paper explores the ethical implications of HIV self-testing. We conclude that there are no strong ethical objections to self-testing being made widely available in the UK. Pretest counselling for an HIV test is not an ethical necessity, and self-testing has the potential to increase early diagnosis of HIV infection and thus improve prognosis and reduce ongoing transmission. Self-testing kits might also empower people and promote autonomy by allowing people to dictate the terms on which they test their HIV status. We accept that there are some potential areas of concern. These include the possibility of user error with the tests, and the concern that individuals may not present to health services following a reactive result. False negatives have the potential to cause harm if the 'window period' is not understood, and false positives might produce psychological distress. There is, however, little evidence to suggest that self-testing kits will cause widespread harm, and we argue that the only way to properly evaluate whether they do cause significant harm is to carefully evaluate their use, now that they are available on the market. PMID- 26276790 TI - Impaired vascular function and repair in patients with premature coronary artery disease. AB - BACKGROUND: Endothelial dysfunction is central to the pathogenesis of coronary artery disease, but the role of local and circulating endothelial progenitor cells in maintaining vascular health is poorly understood. We hypothesised that impaired local and circulating vascular repair mechanisms predispose to endothelial dysfunction and the premature onset of coronary artery disease. METHODS AND RESULTS: Patients with premature coronary artery disease (n = 16) and healthy age- and sex-matched controls (n = 16) underwent venous occlusion plethysmography with intra-arterial infusion of acetylcholine and sodium nitroprusside. Numbers of circulating endothelial progenitor cells were directly quantified in whole blood by flow cytometry. Endothelial cells were isolated from the blood vessel wall and from peripheral blood mononuclear cells, and expanded in vitro for phenotypic and functional characterisation and analysis of microRNA expression levels. A dose-dependent increase in forearm blood flow (p < 0.001) was attenuated in response to the endothelial-dependent vasodilator acetylcholine in patients compared with controls (p = 0.03). No differences in the number of circulating endothelial progenitor cells or in the phenotype, function or microRNA expression levels of endothelial outgrowth cells isolated from blood were observed in patients and controls. Conversely, local vessel wall endothelial cells from patients had significant impairments in proliferation, adhesion and migration, and significantly reduced expression levels of microRNAs known to regulate endothelial function (miRs -10 a, -let7b, -126 and -181 b) (p < 0.05 for all). CONCLUSION: Local vessel wall derived endothelial cells, rather than circulating endothelial progenitor cells and their progeny, are impaired in patients with vascular dysfunction and premature coronary artery disease. PMID- 26276792 TI - What is publication bias in a meta-analysis? PMID- 26276791 TI - Apelin and Visfatin Plasma Levels in Healthy Individuals With High Normal Blood Pressure. AB - BACKGROUND: High normal blood pressure (BP; 130-139/85-89 mm Hg) is related with increased cardiovascular (CV) risk compared to normal BP (120-129/80-84 mm Hg) or/and optimal BP (<120/80 mm Hg). Low apelin plasma levels have been associated with arterial hypertension and atherosclerosis, while high visfatin plasma levels may promote vascular inflammation and atherosclerotic plaque destabilization and have been evaluated as a marker for identifying stages of essential hypertension. We sought to compare the apelin and visfatin plasma levels between subjects with high normal BP and subjects with normal or optimal BP matched for age, gender, smoking, and body mass index (BMI). METHODS: Twenty-five subjects with high normal BP (office BP 136+/-3/88+/-2 mm Hg, age 57+/-4 years, 76% males, 32% smokers, BMI 24.0+/-1.7 kg/m2) and 35 subjects with normal or optimal BP (office BP 118+/-2/78+/-2 mm Hg, age 55+/-7 years, 63% males, 29% smokers, BMI 23.2+/-1.4 kg/m2) were studied. The apelin and visfatin plasma levels were determined with the enzyme-linked immunosorbent assay. RESULTS: Compared to normal or optimal BP subjects, apelin levels were significantly lower (205+/-108 vs. 325+/-152 pg/ml, P < 0.001) and visfatin levels significantly higher (11.0+/-2.0 vs. 7.2+/-0.9 ng/ml, P = 0.002) in high normal BP subjects. No significant differences were found between the 2 groups (P = NS) regarding the basic clinical characteristics, the glycemic/lipid profile, and the renal function parameters. CONCLUSIONS: The emerging, from the present study, data raise the hypothesis that lower apelin and higher visfatin plasma levels in high normal BP subjects compared to normal or optimal BP individuals could partially explain the higher CV risk of the high normal BP group. PMID- 26276794 TI - Designing a spoken dialogue interface to an intelligent cognitive assistant for people with dementia. AB - Intelligent cognitive assistants support people who need help performing everyday tasks by detecting when problems occur and providing tailored and context sensitive assistance. Spoken dialogue interfaces allow users to interact with intelligent cognitive assistants while focusing on the task at hand. In order to establish requirements for voice interfaces to intelligent cognitive assistants, we conducted three focus groups with people with dementia, carers, and older people without a diagnosis of dementia. Analysis of the focus group data showed that voice and interaction style should be chosen based on the preferences of the user, not those of the carer. For people with dementia, the intelligent cognitive assistant should act like a patient, encouraging guide, while for older people without dementia, assistance should be to the point and not patronising. The intelligent cognitive assistant should be able to adapt to cognitive decline. PMID- 26276795 TI - Implementation factors affecting the large-scale deployment of digital health and well-being technologies: A qualitative study of the initial phases of the 'Living It-Up' programme. AB - Little is known about the factors which facilitate or impede the large-scale deployment of health and well-being consumer technologies. The Living-It-Up project is a large-scale digital intervention led by NHS 24, aiming to transform health and well-being services delivery throughout Scotland. We conducted a qualitative study of the factors affecting the implementation and deployment of the Living-It-Up services. We collected a range of data during the initial phase of deployment, including semi-structured interviews (N = 6); participant observation sessions (N = 5) and meetings with key stakeholders (N = 3). We used the Normalisation Process Theory as an explanatory framework to interpret the social processes at play during the initial phases of deployment.Initial findings illustrate that it is clear - and perhaps not surprising - that the size and diversity of the Living-It-Up consortium made implementation processes more complex within a 'multi-stakeholder' environment. To overcome these barriers, there is a need to clearly define roles, tasks and responsibilities among the consortium partners. Furthermore, varying levels of expectations and requirements, as well as diverse cultures and ways of working, must be effectively managed. Factors which facilitated implementation included extensive stakeholder engagement, such as co-design activities, which can contribute to an increased 'buy-in' from users in the long term. An important lesson from the Living-It-Up initiative is that attempting to co-design innovative digital services, but at the same time, recruiting large numbers of users is likely to generate conflicting implementation priorities which hinder - or at least substantially slow down - the effective rollout of services at scale.The deployment of Living-It-Up services is ongoing, but our results to date suggest that - in order to be successful - the roll-out of digital health and well-being technologies at scale requires a delicate and pragmatic trade-off between co design activities, the development of innovative services and the efforts allocated to widespread marketing and recruitment initiatives. PMID- 26276796 TI - Integration of healthcare and financial information: Evaluation in a public hospital using a comprehensive approach. AB - Public healthcare organisations are moving towards the use of new technologies to automate and improve their internal processes in order to increase the effectiveness and efficiency of their use of resources. The aim of this research is to tackle the systematic evaluation of an experience of integrating information in a healthcare organisation, paying attention to the implications that this entails. The results show that the integration of the information in the hospital results in higher levels of quality. This study contributes a vision of interrelated work, in which tasks are shared and aims are jointly established. PMID- 26276797 TI - Targets to promote swimming between the flags among Australian beachgoers. AB - Visiting the beach is a popular activity, but the risk of drowning is real. Drownings are preventable, and swimming between the patrol flags can save lives. The aim of this study is to understand the beliefs people hold in relation to this important water safety behaviour. Participants (N= 514; females = 58%) who were residents of/visitors to coastal areas in South-East Queensland, Australia, completed a theory of planned behaviour belief-based questionnaire. The survey was designed to measure behavioural, normative and control beliefs guiding beachgoers' intentions to swim between the patrol flags. Controlling for age, gender and swimming ability, four critical beliefs (along with self-reported swimming ability) were identified as independently predicting intention. Specifically, the benefits of feeling safe and the cost of feeling limited in choice of where to swim, the social approval from partners and the inhibitor belief about better waves being outside the flags predicted intentions to swim between the flags. This study provides an understanding of the beliefs underlying Australian beachgoers' intentions to swim between the patrol flags. Attention to these targeted beliefs may assist in promoting more regular performance of this beach safety behaviour, thereby combating the increasing rates of drownings and surf rescues. PMID- 26276798 TI - With or without the group: Swedish midwives' and child healthcare nurses' experiences in leading parent education groups. AB - The aim of the study was to describe and to understand midwives' and child healthcare nurses' experiences of working with parent education groups through their descriptions of the role and what they find rewarding and challenging in that work. Data were collected through three open-ended questions from a web survey: 'How do you refer to your role when working in parent education?', 'What is the biggest challenge or difficulty for you when working in parent education?' and 'What is most rewarding when working in parent education?' The answers were analysed by using qualitative content analysis and correlation analysis. The results show that the midwives and child healthcare nurses either included or excluded the group when describing their role as leaders and their influence on parents. The same applies to what they found rewarding and what was difficult and challenging for them in working with the groups. Primarily, the leaders who excluded the group expressed a lack of competence on a professional level in managing groups and using the right teaching methods to process the knowledge content. One important question to deal with is how to best support midwives and nurses in child healthcare to be prepared for working with parent education groups. One obvious thing is to provide specialized training in an educational sense. An important aspect could also be providing supervision, individually or in groups. PMID- 26276799 TI - Young adults: beloved by food and drink marketers and forgotten by public health? AB - Young adults are a highly desirable target population for energy-dense, nutrient poor (EDNP) food and beverage marketing. But little research, resources, advocacy and policy action have been directed at this age group, despite the fact that young adults are gaining weight faster than previous generations and other population groups. Factors such as identity development and shifting interpersonal influences differentiate young adulthood from other life stages and influence the adoption of both healthy and unhealthy eating behaviours. EDNP food and beverage marketing campaigns use techniques to normalize brands within young adult culture, in particular through online social media. Young adults must be a priority population in future obesity prevention efforts. Stronger policies to protect young adults from EDNP food and beverage marketing may also increase the effectiveness of policies that are meant to protect younger children. Restrictions on EDNP food and beverage marketing should be extended to include Internet-based advertising and also aim to protect vulnerable young adults. PMID- 26276800 TI - Health in All Policies in South Australia: what has supported early implementation? AB - Health in All Policies (HiAP) is a policy development approach that facilitates intersectoral responses to addressing the social determinants of health and health equity whilst, at the same time, contributing to policy priorities across the various sectors of government. Given that different models of HiAP have been implemented in at least 16 countries, there is increasing interest in how its effectiveness can be optimized. Much of the existing literature on HiAP remains descriptive, however, and lacks critical, empirically informed analyses of the elements that support implementation. Furthermore, literature on HiAP, and intersectoral action more generally, provides little detail on the practical workings of policy collaborations. This paper contributes empirical findings from a multi-method study of HiAP implementation in South Australia (SA) between 2007 and 2013. It considers the views of public servants and presents analysis of elements that have supported, and impeded, implementation of HiAP in SA. We found that HiAP has been implemented in SA using a combination of interrelated elements. The operation of these elements has provided a strong foundation, which suggests the potential for HiAP to extend beyond being an isolated strategy, to form a more integrated and systemic mechanism of policy-making. We conclude with learnings from the SA experience of HiAP implementation to inform the ongoing development and implementation of HiAP in SA and internationally. PMID- 26276801 TI - Junior doctors will not re-enter contract negotiations with government. PMID- 26276802 TI - A glyS T-box riboswitch with species-specific structural features responding to both proteinogenic and nonproteinogenic tRNAGly isoacceptors. AB - In Staphylococcus aureus, a T-box riboswitch exists upstream of the glyS gene to regulate transcription of the sole glycyl-tRNA synthetase, which aminoacylates five tRNA(Gly) isoacceptors bearing GCC or UCC anticodons. Subsequently, the glycylated tRNAs serve as substrates for decoding glycine codons during translation, and also as glycine donors for exoribosomal synthesis of pentaglycine peptides during cell wall formation. Probing of the predicted T-box structure revealed a long stem I, lacking features previously described for similar T-boxes. Moreover, the antiterminator stem includes a 42-nt long intervening sequence, which is staphylococci-specific. Finally, the terminator conformation adopts a rigid two-stem structure, where the intervening sequence forms the first stem followed by the second stem, which includes the more conserved residues. Interestingly, all five tRNA(Gly) isoacceptors interact with S. aureus glyS T-box with different binding affinities and they all induce transcription readthrough at different levels. The ability of both GCC and UCC anticodons to interact with the specifier loop indicates ambiguity during the specifier triplet reading, similar to the unconventional reading of glycine codons during protein synthesis. The S. aureus glyS T-box structure is consistent with the recent crystallographic and NMR studies, despite apparent differences, and highlights the phylogenetic variability of T-boxes when studied in a genome dependent context. Our data suggest that the S. aureus glyS T-box exhibits differential tRNA selectivity, which possibly contributes toward the regulation and synchronization of ribosomal and exoribosomal peptide synthesis, two essential but metabolically unrelated pathways. PMID- 26276804 TI - Cardiac magnetic resonance markers of progressive RV dilation and dysfunction after tetralogy of Fallot repair. AB - OBJECTIVE: Patients with repaired tetralogy of Fallot (TOF) are followed serially by cardiac magnetic resonance (CMR) for surveillance of RV dilation and dysfunction. We sought to define the prevalence of progressive RV disease and the optimal time interval between CMR evaluations. METHODS: Candidates were selected from a multicentre TOF registry and were included if >=2 CMR studies performed >=6 months apart were available without interval cardiovascular interventions. Patients with 'disease progression' (defined as increase in RV end-diastolic volume index (RVEDVi) >=30 mL/m(2), decrease in RVEF >=10% or decrease in LVEF >=10%) were compared with those with 'disease non-progression' (defined as RVEDVi increase <=5 mL/m(2), RVEF decrease <=3% and LVEF decrease <=3%). RESULTS: A total of 849 CMR studies in 339 patients (median age at first CMR 23.6 years) were analysed. Over a median interval of 2.2 years between CMR pairs, RVEDVi increased 4+/-18 mL/m(2) (p<0.001), RV end-systolic volume index increased 3+/-13 mL/m(2) (p<0.001), RVEF decreased 1%+/-6% (p=0.02) and LVEF decreased 1%+/-6% (p=0.001). Disease progression was observed in 15% (n=76) and non-progression in 26% (n=133). There were no significant differences between those with and without progression in baseline demographic, anatomic, ECG, exercise or baseline CMR characteristics. The optimal time interval between CMR studies for detection of progression was a 3-year interval (63% sensitivity, 65% specificity, area under the receiver operating characteristic curve 0.65). CONCLUSIONS: Although progressive RV dilation and decline in biventricular systolic function occur at a slow pace in the majority of adults with repaired TOF, 15% of patients experience rapid disease progression. The results of this study support the practice of serial CMR examinations to identify progressive disease at a time interval of up to 3 years. PMID- 26276805 TI - A not so typical pericardial effusion case.... PMID- 26276806 TI - Exercise Improves Physical Function and Mental Health of Brain Cancer Survivors: Two Exploratory Case Studies. AB - Background Malignant brain tumors are unpredictable and incurable, with 5-year survival rates less than 30%. The poor prognosis combined with intensive treatment necessitates the inclusion of complementary and supportive therapies that optimize quality of life and reduce treatment-related declines in health. Exercise therapy has been shown to be beneficial in other cancer populations, but no evidence is available for brain cancer survivors. Therefore, we report results from 2 preliminary cases. Methods Two female patients diagnosed with glioblastoma multiforme and oligodendroglioma participated in a structured and supervised 12 week exercise program. The program consisted of two 1-hour resistance and aerobic exercise sessions per week and additional self-managed aerobic sessions. Outcome measures of strength, cardiovascular fitness, and several psychological indicators (depression, anxiety, and quality of life) were recorded at baseline, after 6 weeks and at the conclusion of the intervention. Results Exercise was well tolerated; both participants completed all 24 sessions and the home-based component with no adverse effects. Objective outcome measures displayed positive responses relating to reduced morbidity. Similar positive responses were found for psychological outcomes. Scores on the Hospital Anxiety and Depression Scale showed clinically meaningful improvements in depression and total distress. Conclusion These findings provide initial evidence that, despite the difficulties associated with brain cancer treatment and survivorship, exercise may be safe and beneficial and should be considered in the overall management of patients with brain cancer. PMID- 26276807 TI - MCNP SIMULATION OF THE HP(10) ENERGY RESPONSE OF A BRAZILIAN TLD ALBEDO NEUTRON INDIVIDUAL DOSEMETER, FROM THERMAL TO 20 MeV. AB - The Brazilian Instituto de Radioprotecao e Dosimetria (IRD) runs a neutron individual monitoring system with a home-made TLD albedo dosemeter. It has already been characterised and calibrated in some reference fields. However, the complete energy response of this dosemeter is not known, and the calibration factors for all monitored workplace neutron fields are difficult to be obtained experimentally. Therefore, to overcome such difficulties, Monte Carlo simulations have been used. This paper describes the simulation of the HP(10) neutron response of the IRD TLD albedo dosemeter using the MCNPX transport code, for energies from thermal to 20 MeV. The validation of the MCNPX modelling is done comparing the simulated results with the experimental measurements for ISO standard neutron fields of (241)Am-Be, (252)Cf, (241)Am-B and (252)Cf(D2O) and also for (241)Am-Be source moderated with paraffin and silicone. Bare (252)Cf are used for normalisation. PMID- 26276808 TI - A SINGLE-EXPOSURE, MULTIDETECTOR NEUTRON SPECTROMETER FOR WORKPLACE MONITORING. AB - This communication describes a recently developed single-exposure neutron spectrometer, based on multiple active thermal neutron detectors located within a moderating sphere, which have been developed jointly by CIEMAT (Spain), INFN (Italy) and Politecnico di Milano (Italy) in the framework of Italian and Spanish collaboration projects. The fabricated prototypes permit to achieve spectrometric resolution with nearly isotropic response for neutron with energies from thermal to 100-200 MeV, thus being able to characterise the complete neutron spectrum in only one exposure by unfolding the measured responses of the detectors. This makes it especially advantageous for characterising neutron fields and workplace monitoring purposes in neutron-producing facilities. PMID- 26276809 TI - Neural signatures of third-party punishment: evidence from penetrating traumatic brain injury. AB - The ability to survive within a cooperative society depends on impartial third party punishment (TPP) of social norm violations. Two cognitive mechanisms have been postulated as necessary for the successful completion of TPP: evaluation of legal responsibility and selection of a suitable punishment given the magnitude of the crime. Converging neuroimaging research suggests two supporting domain general networks; a mentalizing network for evaluation of legal responsibility and a central-executive network for determination of punishment. A whole-brain voxel-based lesion-symptom mapping approach was used in conjunction with a rank order TPP task to identify brain regions necessary for TPP in a large sample of patients with penetrating traumatic brain injury. Patients who demonstrated atypical TPP had specific lesions in core regions of the mentalizing (dorsomedial prefrontal cortex [PFC], ventromedial PFC) and central-executive (bilateral dorsolateral PFC, right intraparietal sulcus) networks. Altruism and executive functioning (concept formation skills) were significant predictors of TPP: altruism was uniquely associated with TPP in patients with lesions in right dorsolateral PFC and executive functioning was uniquely associated with TPP in individuals with lesions in left PFC. Our findings contribute to the extant literature to support underlying neural networks associated with TPP, with specific brain-behavior causal relationships confirming recent functional neuroimaging research. PMID- 26276811 TI - Glial TDP-43 regulates axon wrapping, GluRIIA clustering and fly motility by autonomous and non-autonomous mechanisms. AB - Alterations in the glial function of TDP-43 are becoming increasingly associated with the neurological symptoms observed in Amyotrophic Lateral Sclerosis (ALS), however, the physiological role of this protein in the glia or the mechanisms that may lead to neurodegeneration are unknown. To address these issues, we modulated the expression levels of TDP-43 in the Drosophila glia and found that the protein was required to regulate the subcellular wrapping of motoneuron axons, promote synaptic growth and the formation of glutamate receptor clusters at the neuromuscular junctions. Interestingly, we determined that the glutamate transporter EAAT1 mediated the regulatory functions of TDP-43 in the glia and demonstrated that genetic or pharmacological compensations of EAAT1 activity were sufficient to modulate glutamate receptor clustering and locomotive behaviors in flies. The data uncovers autonomous and non-autonomous functions of TDP-43 in the glia and suggests new experimentally based therapeutic strategies in ALS. PMID- 26276810 TI - Tau deposition drives neuropathological, inflammatory and behavioral abnormalities independently of neuronal loss in a novel mouse model. AB - Aberrant tau protein accumulation drives neurofibrillary tangle (NFT) formation in several neurodegenerative diseases. Currently, efforts to elucidate pathogenic mechanisms and assess the efficacy of therapeutic targets are limited by constraints of existing models of tauopathy. In order to generate a more versatile mouse model of tauopathy, somatic brain transgenesis was utilized to deliver adeno-associated virus serotype 1 (AAV1) encoding human mutant P301L-tau compared with GFP control. At 6 months of age, we observed widespread human tau expression with concomitant accumulation of hyperphosphorylated and abnormally folded proteinase K resistant tau. However, no overt neuronal loss was observed, though significant abnormalities were noted in the postsynaptic scaffolding protein PSD95. Neurofibrillary pathology was also detected with Gallyas silver stain and Thioflavin-S, and electron microscopy revealed the deposition of closely packed filaments. In addition to classic markers of tauopathy, significant neuroinflammation and extensive gliosis were detected in AAV1 Tau(P301L) mice. This model also recapitulates the behavioral phenotype characteristic of mouse models of tauopathy, including abnormalities in exploration, anxiety, and learning and memory. These findings indicate that biochemical and neuropathological hallmarks of tauopathies are accurately conserved and are independent of cell death in this novel AAV-based model of tauopathy, which offers exceptional versatility and speed in comparison with existing transgenic models. Therefore, we anticipate this approach will facilitate the identification and validation of genetic modifiers of disease, as well as accelerate preclinical assessment of potential therapeutic targets. PMID- 26276813 TI - Unregulated usage of labour-inducing medication in a region of Pakistan with poor drug regulatory control: characteristics and risk patterns. AB - BACKGROUND: In developing countries such as Pakistan, poor training of mid-level cadres of health providers, combined with unregulated availability of labour inducing medication can carry considerable risk for mother and child during labour. Here, we describe the exposure to labour-inducing medication and its possible risks in a vulnerable population in a conflict-affected region of Pakistan. METHODS: A retrospective cohort study using programme data, compared the outcomes of obstetric risk groups of women treated with unregulated oxytocin, with those of women with regulated treatment. RESULTS: Of the 6379 women included in the study, 607 (9.5%) received labour-inducing medication prior to reaching the hospital; of these, 528 (87.0%) received unregulated medication. Out of 528 labour-inducing medication administrators, 197 (37.3%) traditional birth attendants (also known as dai) and 157 (29.7%) lady health workers provided unregulated treatment most frequently. Women given unregulated medication who were diagnosed with obstructed/prolonged labour were at risk for uterine rupture (RR 4.1, 95% CI: 1.7-9.9) and severe birth asphyxia (RR 3.9, 95% CI: 2.5-6.1), and those with antepartum haemorrhage were at risk for stillbirth (RR 1.8, 95% CI: 1.0-3.1). CONCLUSIONS: In a conflict-affected region of Pakistan, exposure to unregulated treatment with labour-inducing medication is common, and carries great risk for mother and child. Tighter regulatory control of labour-inducing drugs is needed, and enhanced training of the mid-level cadres of healthcare workers is required. PMID- 26276812 TI - Low levels of Survival Motor Neuron protein are sufficient for normal muscle function in the SMNDelta7 mouse model of SMA. AB - Spinal Muscular Atrophy (SMA) is an autosomal recessive disorder characterized by loss of lower motor neurons. SMA is caused by deletion or mutation of the Survival Motor Neuron 1 (SMN1) gene and retention of the SMN2 gene. The loss of SMN1 results in reduced levels of the SMN protein. SMN levels appear to be particularly important in motor neurons; however SMN levels above that produced by two copies of SMN2 have been suggested to be important in muscle. Studying the spatial requirement of SMN is important in both understanding how SMN deficiency causes SMA and in the development of effective therapies. Using Myf5-Cre, a muscle-specific Cre driver, and the Cre-loxP recombination system, we deleted mouse Smn in the muscle of mice with SMN2 and SMNDelta7 transgenes in the background, thus providing low level of SMN in the muscle. As a reciprocal experiment, we restored normal levels of SMN in the muscle with low SMN levels in all other tissues. We observed that decreasing SMN in the muscle has no phenotypic effect. This was corroborated by muscle physiology studies with twitch force, tetanic and eccentric contraction all being normal. In addition, electrocardiogram and muscle fiber size distribution were also normal. Replacement of Smn in muscle did not rescue SMA mice. Thus the muscle does not appear to require high levels of SMN above what is produced by two copies of SMN2 (and SMNDelta7). PMID- 26276814 TI - Relation between QT interval variability and muscle sympathetic nerve activity in normal subjects. AB - Beat-to-beat variability of the QT interval (QTV) is sought to provide an indirect noninvasive measure of sympathetic nerve activity, but a formal quantification of this relationship has not been provided. In this study we used power contribution analysis to study the relationship between QTV and muscle sympathetic nerve activity (MSNA). ECG and MSNA were recorded in 10 healthy subjects in the supine position and after 40 degrees head-up tilt. Power spectrum analysis was performed using a linear autoregressive model with two external inputs: heart period (RR interval) variability (RRV) and MSNA. Total and low-frequency power of QTV was decomposed into contributions by RRV, MSNA, and sources independent of RRV and MSNA. Results show that the percentage of MSNA power contribution to QT is very small and does not change with tilt. RRV power contribution to QT power is notable and decreases with tilt, while the greatest percentage of QTV is independent of RRV and MSNA in the supine position and after 40 degrees head-up tilt. In conclusion, beat-to-beat QTV in normal subjects does not appear to be significantly affected by the rhythmic modulations in MSNA following low to moderate orthostatic stimulation. Therefore, MSNA oscillations may not represent a useful surrogate for cardiac sympathetic nerve activity at moderate levels of activation, or, alternatively, sympathetic influences on QTV are complex and not quantifiable with linear shift-invariant autoregressive models. PMID- 26276815 TI - Dynamics of enhanced mitochondrial respiration in female compared with male rat cerebral arteries. AB - Mitochondrial respiration has never been directly examined in intact cerebral arteries. We tested the hypothesis that mitochondrial energetics of large cerebral arteries ex vivo are sex dependent. The Seahorse XFe24 analyzer was used to examine mitochondrial respiration in isolated cerebral arteries from adult male and female Sprague-Dawley rats. We examined the role of nitric oxide (NO) on mitochondrial respiration under basal conditions, using N(omega)-nitro-l-arginine methyl ester, and following pharmacological challenge using diazoxide (DZ), and also determined levels of mitochondrial and nonmitochondrial proteins using Western blot, and vascular diameter responses to DZ. The components of mitochondrial respiration including basal respiration, ATP production, proton leak, maximal respiration, and spare respiratory capacity were elevated in females compared with males, but increased in both male and female arteries in the presence of the NOS inhibitor. Although acute DZ treatment had little effect on mitochondrial respiration of male arteries, it decreased the respiration in female arteries. Levels of mitochondrial proteins in Complexes I-V and the voltage-dependent anion channel protein were elevated in female compared with male cerebral arteries. The DZ-induced vasodilation was greater in females than in males. Our findings show that substantial sex differences in mitochondrial respiratory dynamics exist in large cerebral arteries and may provide the mechanistic basis for observations that the female cerebral vasculature is more adaptable after injury. PMID- 26276816 TI - Associations and clinical relevance of aortic-brachial artery stiffness mismatch, aortic reservoir function, and central pressure augmentation. AB - Central augmentation pressure (AP) and index (AIx) predict cardiovascular events and mortality, but underlying physiological mechanisms remain disputed. While traditionally believed to relate to wave reflections arising from proximal arterial impedance (and stiffness) mismatching, recent evidence suggests aortic reservoir function may be a more dominant contributor to AP and AIx. Our aim was therefore to determine relationships among aortic-brachial stiffness mismatching, AP, AIx, aortic reservoir function, and end-organ disease. Aortic (aPWV) and brachial (bPWV) pulse wave velocity were measured in 359 individuals (aged 61 +/- 9, 49% male). Central AP, AIx, and aortic reservoir indexes were derived from radial tonometry. Participants were stratified by positive (bPWV > aPWV), negligible (bPWV ~ aPWV), or negative stiffness mismatch (bPWV < aPWV). Left ventricular mass index (LVMI) was measured by two-dimensional-echocardiography. Central AP and AIx were higher with negative stiffness mismatch vs. negligible or positive stiffness mismatch (11 +/- 6 vs. 10 +/- 6 vs. 8 +/- 6 mmHg, P < 0.001 and 24 +/- 10 vs. 24 +/- 11 vs. 21 +/- 13%, P = 0.042). Stiffness mismatch (bPWV aPWV) was negatively associated with AP (r = -0.18, P = 0.001) but not AIx (r = 0.06, P = 0.27). Aortic reservoir pressure strongly correlated to AP (r = 0.81, P < 0.001) and AIx (r = 0.62, P < 0.001) independent of age, sex, heart rate, mean arterial pressure, and height (standardized beta = 0.61 and 0.12, P <= 0.001). Aortic reservoir pressure independently predicted abnormal LVMI (beta = 0.13, P = 0.024). Positive aortic-brachial stiffness mismatch does not result in higher AP or AIx. Aortic reservoir function, rather than discrete wave reflection from proximal arterial stiffness mismatching, provides a better model description of AP and AIx and also has clinical relevance as evidenced by an independent association of aortic reservoir pressure with LVMI. PMID- 26276817 TI - Angiopoietin-1 prevents severe bleeding complications induced by heparin-like drugs and fibroblast growth factor-2 in mice. AB - Critically ill children can develop bleeding complications when treated with heparin-like drugs. These events are usually attributed to the anticoagulant activity of these drugs. However, previous studies showed that fibroblast growth factor-2 (FGF-2), a heparin-binding growth factor released in the circulation of these patients, could precipitate intestinal hemorrhages in mice treated with the heparin-like drug pentosan polysulfate (PPS). Yet very little is known about how FGF-2 induces bleeding complications in combination with heparin-like drugs. Here, we examined the mechanisms by which circulating FGF-2 induces intestinal hemorrhages in mice treated with PPS. We used a well-characterized mouse model of intestinal hemorrhages induced by FGF-2 plus PPS. Adult FVB/N mice were infected with adenovirus carrying Lac-Z or a secreted form of recombinant human FGF-2, and injected with PPS, at doses that do not induce bleeding complications per se. Mice treated with FGF-2 in combination with PPS developed an intestinal inflammatory reaction that increased the permeability and disrupted the integrity of submucosal intestinal vessels. These changes, together with the anticoagulant activity of PPS, induced lethal hemorrhages. Moreover, a genetically modified form of the endothelial ligand angiopoietin-1 (Ang-1*), which has powerful antipermeability and anti-inflammatory activity, prevented the lethal bleeding complications without correcting the anticoagulant status of these mice. These findings define new mechanisms through which FGF-2 and Ang-1* modulate the outcome of intestinal bleeding complications induced by PPS in mice and may have wider clinical implications for critically ill children treated with heparin-like drugs. PMID- 26276818 TI - Vagus nerve stimulation mitigates intrinsic cardiac neuronal and adverse myocyte remodeling postmyocardial infarction. AB - This paper aims to determine whether chronic vagus nerve stimulation (VNS) mitigates myocardial infarction (MI)-induced remodeling of the intrinsic cardiac nervous system (ICNS), along with the cardiac tissue it regulates. Guinea pigs underwent VNS implantation on the right cervical vagus. Two weeks later, MI was produced by ligating the ventral descending coronary artery. VNS stimulation started 7 days post-MI (20 Hz, 0.9 +/- 0.2 mA, 14 s on, 48 s off; VNS-MI, n = 7) and was compared with time-matched MI animals with sham VNS (MI n = 7) vs. untreated controls (n = 8). Echocardiograms were performed before and at 90 days post-MI. At termination, IC neuronal intracellular voltage recordings were obtained from whole-mount neuronal plexuses. MI increased left ventricular end systolic volume (LVESV) 30% (P = 0.027) and reduced LV ejection fraction (LVEF) 6.5% (P < 0.001) at 90 days post-MI compared with baseline. In the VNS-MI group, LVESV and LVEF did not differ from baseline. IC neurons showed depolarization of resting membrane potentials and increased input resistance in MI compared with VNS-MI and sham controls (P < 0.05). Neuronal excitability and sensitivity to norepinephrine increased in MI and VNS-MI groups compared with controls (P < 0.05). Synaptic efficacy, as determined by evoked responses to stimulating input axons, was reduced in VNS-MI compared with MI or controls (P < 0.05). VNS induced changes in myocytes, consistent with enhanced glycogenolysis, and blunted the MI induced increase in the proapoptotic Bcl-2-associated X protein (P < 0.05). VNS mitigates MI-induced remodeling of the ICNS, correspondingly preserving ventricular function via both neural and cardiomyocyte-dependent actions. PMID- 26276819 TI - Chloride intracellular channel 4 is required for maturation of the cerebral collateral circulation. AB - The number and diameter of native collaterals in tissues of healthy mice vary widely, resulting in large differences in tissue injury in occlusive diseases. Recent studies suggest similar variation may exist in humans. Collateral variation in mice is determined by genetic background-dependent differences in embryonic collateral formation, by variation in maturation of the nascent collaterals, and by environmental factors such as aging that cause collateral rarefaction in the adult. Recently, formation of the collateral circulation in the brain was found to involve a unique VEGF-A-dependent "arteriolar" angiogenic sprouting-like mechanism. Elsewhere, chloride intracellular protein 4 (CLIC4) was implicated but not investigated directly, prompting the present study. Deletion of Clic4 had no effect on embryonic collaterogenesis. However, during collateral maturation from embryonic day 18.5 to postnatal day 7, reduced mural cell investment was observed and excessive pruning of collaterals occurred. Growth in collateral diameter was reduced. This resulted in 50% fewer collaterals of smaller diameter in the adult and thus larger infarct volume after middle cerebral artery occlusion. During collateral maturation, CLIC4 deficiency resulted in reduced expression of Vegfr2, Vegfr1, Vegfc, and mural cell markers, but not notch-pathway genes. Overexpression of VEGF-A in Clic4(-/-) mice had no effect on collaterogenesis, but rescued the above defects in collateral maturation by preventing mural cell loss and collateral pruning, thus restoring collateral number and diameter and reducing stroke severity in the adult. CLIC4 is not required for collaterogenesis but is essential for perinatal maturation of nascent collaterals through a mechanism that supports VEGF signaling. PMID- 26276820 TI - Mitochondrial flash as a novel biomarker of mitochondrial respiration in the heart. AB - Mitochondrial respiration through electron transport chain (ETC) activity generates ATP and reactive oxygen species in eukaryotic cells. The modulation of mitochondrial respiration in vivo or under physiological conditions remains elusive largely due to the lack of appropriate approach to monitor ETC activity in a real-time manner. Here, we show that ETC-coupled mitochondrial flash is a novel biomarker for monitoring mitochondrial respiration under pathophysiological conditions in cultured adult cardiac myocyte and perfused beating heart. Through real-time confocal imaging, we follow the frequency of a transient bursting fluorescent signal, named mitochondrial flash, from individual mitochondria within intact cells expressing a mitochondrial matrix-targeted probe, mt-cpYFP (mitochondrial-circularly permuted yellow fluorescent protein). This mt-cpYFP recorded mitochondrial flash has been shown to be composed of a major superoxide signal with a minor alkalization signal within the mitochondrial matrix. Through manipulating physiological substrates for mitochondrial respiration, we find a close coupling between flash frequency and the ETC electron flow, as measured by oxygen consumption rate in cardiac myocyte. Stimulating electron flow under physiological conditions increases flash frequency. On the other hand, partially block or slowdown electron flow by inhibiting the F0F1 ATPase, which represents a pathological condition, transiently increases then decreases flash frequency. Limiting electron entrance at complex I by knocking out Ndufs4, an assembling subunit of complex I, suppresses mitochondrial flash activity. These results suggest that mitochondrial electron flow can be monitored by real-time imaging of mitochondrial flash. The mitochondrial flash frequency could be used as a novel biomarker for mitochondrial respiration under physiological and pathological conditions. PMID- 26276821 TI - Axl modulates immune activation of smooth muscle cells in vein graft remodeling. AB - The pathophysiological mechanisms of the immune activation of smooth muscle cells are not well understood. Increased expression of Axl, a receptor tyrosine kinase, was recently found in arteries from patients after coronary bypass grafts. In the present study, we hypothesized that Axl-dependent immune activation of smooth muscle cells regulates vein graft remodeling. We observed a twofold decrease in intimal thickening after vascular and systemic depletion of Axl in vein grafts. Local depletion of Axl had the greatest effect on immune activation, whereas systemic deletion of Axl reduced intima due to an increase in apoptosis in vein grafts. Primary smooth muscle cells isolated from Axl knockout mice had reduced proinflammatory responses by prevention of the STAT1 pathway. The absence of Axl increased suppressor of cytokine signaling (SOCS)1 expression in smooth muscle cells, a major inhibitory protein for STAT1. Ultrasound imaging suggested that vascular depletion of Axl reduced vein graft stiffness. Axl expression determined the STAT1-SOCS1 balance in vein graft intima and progression of the remodeling. The results of this investigation demonstrate that Axl promotes STAT1 signaling via inhibition of SOCS1 in activated smooth muscle cells in vein graft remodeling. PMID- 26276822 TI - Prevention of vascular dysfunction and arterial hypertension in mice generated by assisted reproductive technologies by addition of melatonin to culture media. AB - Assisted reproductive technologies (ART) induce vascular dysfunction in humans and mice. In mice, ART-induced vascular dysfunction is related to epigenetic alteration of the endothelial nitric oxide synthase (eNOS) gene, resulting in decreased vascular eNOS expression and nitrite/nitrate synthesis. Melatonin is involved in epigenetic regulation, and its administration to sterile women improves the success rate of ART. We hypothesized that addition of melatonin to culture media may prevent ART-induced epigenetic and cardiovascular alterations in mice. We, therefore, assessed mesenteric-artery responses to acetylcholine and arterial blood pressure, together with DNA methylation of the eNOS gene promoter in vascular tissue and nitric oxide plasma concentration in 12-wk-old ART mice generated with and without addition of melatonin to culture media and in control mice. As expected, acetylcholine-induced mesenteric-artery dilation was impaired (P = 0.008 vs. control) and mean arterial blood pressure increased (109.5 +/- 3.8 vs. 104.0 +/- 4.7 mmHg, P = 0.002, ART vs. control) in ART compared with control mice. These alterations were associated with altered DNA methylation of the eNOS gene promoter (P < 0.001 vs. control) and decreased plasma nitric oxide concentration (10.1 +/- 11.1 vs. 29.5 +/- 8.0 MUM) (P < 0.001 ART vs. control). Addition of melatonin (10(-6) M) to culture media prevented eNOS dysmethylation (P = 0.005, vs. ART + vehicle), normalized nitric oxide plasma concentration (23.1 +/- 14.6 MUM, P = 0.002 vs. ART + vehicle) and mesentery-artery responsiveness to acetylcholine (P < 0.008 vs. ART + vehicle), and prevented arterial hypertension (104.6 +/- 3.4 mmHg, P < 0.003 vs. ART + vehicle). These findings provide proof of principle that modification of culture media prevents ART-induced vascular dysfunction. We speculate that this approach will also allow preventing ART-induced premature atherosclerosis in humans. PMID- 26276824 TI - Is Monoglucosyldiacylglycerol a Precursor to Monogalactosyldiacylglycerol in All Cyanobacteria? AB - Monogalactosyldiacylglycerol (MGDG) is ubiquitous in the photosynthetic membranes of cyanobacteria and chloroplasts. It is synthesized by galactosylation of diacylglycerol (DAG) in the chloroplasts, whereas it is produced by epimerization of monoglucosyldiacylglycerol (GlcDG) in at least several cyanobacteria that have been analyzed such as Synechocystis sp. PCC 6803. A previous study, however, showed that the mgdE gene encoding the epimerase is absent in some cyanobacteria such as Gloeobacter violaceus, Thermosynechococcus elongatus and Acaryochloris marina. In addition, the N-terminal 'fatty acid hydroxylase' domain is lacking in the MgdE protein of Prochlorococcus marinus. These problems may cast doubt upon the general (or exclusive) role of MgdE in the epimerization of GlcDG to MGDG in cyanobacteria. In addition, GlcDG is usually present at a very low level, and the structural determination of endogenous GlcDG has not been accomplished with cyanobacterial samples. In this study, I determined the structure of GlcDG from Anabaena variabilis by (1)H- and (13)C-nuclear magnetic resonance (NMR) spectroscopy. I then showed that G. violaceus, T. elongatus, A. marina and P. marinus contain GlcDG. In all cases, GlcDG consisted of fewer unsaturated molecular species than MGDG, providing further evidence that GlcDG is a precursor to MGDG. The conversion of GlcDG to MGDG was also demonstrated by radiolabeling and chase experiments in G. violaceus and P. marinus. These results demonstrate that all the analyzed cyanobacteria contain GlcDG, which is converted to MGDG, and suggest that an alternative epimerase is required for MGDG synthesis in these cyanobacteria. PMID- 26276823 TI - AMP-activated protein kinase inhibits transforming growth factor-beta-mediated vascular smooth muscle cell growth: implications for a Smad-3-dependent mechanism. AB - Dysfunctional vascular growth is a major contributor to cardiovascular disease, the leading cause of morbidity and mortality worldwide. Growth factor-induced activation of vascular smooth muscle cells (VSMCs) results in a phenotypic switch from a quiescent, contractile state to a proliferative state foundational to vessel pathology. Transforming growth factor-beta (TGF-beta) is a multifunctional signaling protein capable of growth stimulation via Smad signaling. Although Smad signaling is well characterized in many tissues, its role in VSM growth disorders remains controversial. Recent data from our lab and others implicate the metabolic regulator AMP-activated protein kinase (AMPK) in VSM growth inhibition. We hypothesized that AMPK inhibits VSMC proliferation by reducing TGF-beta mediated growth in a Smad-dependent fashion. Treatment of rat VSMCs with the AMPK agonist AICAR significantly decreased TGF-beta-mediated activation of synthetic Smad2 and Smad3 and increased inhibitory Smad7. Flow cytometry and automated cell counting revealed that AICAR reversed TGF-beta-mediated cell cycle progression at 24 h and elevated cell numbers at 48 h. TGF-beta/Smad signaling increased the G0/G1 inducers cyclin D1/cyclin-dependent kinase (CDK) 4 and cyclin E/CDK2; however, AICAR reversed these events while increasing cytostatic p21. The specific role of Smad3 in AMPK-mediated reversal of TGF-beta-induced growth was then explored using adenovirus-mediated Smad3 overexpression (Ad-Smad3). Ad-Smad3 cells increased cell cycle progression and cell numbers compared with Ad-GFP control cells, and these were restored to basal levels with concomitant AICAR treatment. These findings support a novel AMPK target in TGF-beta/Smad3 for VSMC growth control and support continued investigation of AMPK as a possible therapeutic target for reducing vascular growth disorders. PMID- 26276825 TI - Methyl Jasmonate-Induced Lipidomic and Biochemical Alterations in the Intertidal Macroalga Gracilaria dura (Gracilariaceae, Rhodophyta). AB - The role of exogenously added methyl jasmonate (MeJA), a lipid-derived signaling compound, in inducing oxidative stress in the marine red macroalga Gracilaria dura was investigated. MeJA at a concentration of 1-100 uM was a strong stimulant of reactive oxygen species (H(2)O(2), HO. and O(2) (.-)) (P < 0.05) causing considerable oxidative stress in G. dura. This further led to lipid peroxidation and degradation of the pigments Chl a and phycocyanin, with a concomitant increase in phycoerythrin. The MeJA-induced oxidative burst also led to the induction of a fatty acid oxidation cascade, resulting in the synthesis of hydroxy-oxylipins and the up-regulation of the 13-lipoxygenase pathway. Electrospray ionization-mass spectrometry-based shotgun lipidomic analysis revealed that monogalactosyldiacylglycerol (a chloroplastic glycerolipid) and phosphatidylcholine (extrachloroplastidic phopholipid) were the most affected lipid classes. The degradation of 18:3-fatty acid-containing monogalactosyldiacylglycerol inferred that it provided fatty acyl chains for the biosynthesis of 13-hydroperoxylinolenic acid, which was further directed towards either the jasmonate pathway or other alternative pathways of the fatty acid oxidation cascade, analogous to higher plants. Also, G. dura modulated the lipid acyl chains in such a way that no significant change was observed in the fatty acid profile of the treated thalli as compared with those of the control, except for C16:0, C16:1 (n-9), C20:3 (n-6) and C20:4 (n-6) (P < 0.05). Furthermore, MeJA caused the accumulation of phenolic compounds and the up-regulation of enzymes involved in secondary metabolism such as polyphenol oxidase, shikimate dehydrogenase and phenylalanine ammonia-lyase, indicating a shift towards secondary metabolism as a defense strategy to combat the induced oxidative stress. PMID- 26276826 TI - Leptin enhances ICAM-1 expression, induces migration and cytokine synthesis, and prolongs survival of human airway epithelial cells. AB - There is rising interest in how obesity affects respiratory diseases, since epidemiological findings indicate a strong relationship between the two conditions. Leptin is a potent adipokine produced mainly by adipocytes. It regulates energy storage and expenditure and also induces inflammation. Previous studies have shown that leptin is able to activate inflammatory cells such as lymphocytes and granulocytes, but little is known about its effect on lung structural cells. The present study investigated the effects of leptin on human airway epithelial cells by using human primary airway epithelial cells and a human airway epithelial cell line, BEAS-2B. Flow cytometry showed enhanced ICAM-1 expression by both of those cells in response to leptin, and that effect was abrogated by dexamethasone or NF-kappaB inhibitor. Flow cytometry and quantitative PCR showed that airway epithelial cells expressed leptin receptor (Ob-R), whose expression level was downregulated by leptin itself. Multiplex cytokine analysis demonstrated enhanced production of CCL11, G-CSF, VEGF, and IL 6 by BEAS-2B cells stimulated with leptin. Furthermore, transfection of Ob-R small interference RNA decreased the effect of leptin on CCL11 production as assessed by quantitative PCR. Finally, leptin induced migration of primary airway epithelial cells toward leptin, suppressed BEAS-2B apoptosis induced with TNF alpha and IFN-gamma, and enhanced proliferation of primary airway epithelial cells. In summary, leptin was able to directly activate human airway epithelial cells by binding to Ob-R and by NF-kappaB activation, resulting in upregulation of ICAM-1 expression, induction of CCL11, VEGF, G-CSF, and IL-6 synthesis, induction of migration, inhibition of apoptosis, and enhancement of proliferation. PMID- 26276827 TI - ROCK insufficiency attenuates ozone-induced airway hyperresponsiveness in mice. AB - Ozone causes airway hyperresponsiveness (AHR) and pulmonary inflammation. Rho kinase (ROCK) is a key regulator of smooth muscle cell contraction and inflammatory cell migration. To determine the contribution of the two ROCK isoforms ROCK1 and ROCK2 to ozone-induced AHR, we exposed wild-type, ROCK1(+/-), and ROCK2(+/-) mice to air or ozone (2 ppm for 3 h) and evaluated mice 24 h later. ROCK1 or ROCK2 haploinsufficiency did not affect airway responsiveness in air-exposed mice but significantly reduced ozone-induced AHR, with a greater reduction in ROCK2(+/-) mice despite increased bronchoalveolar lavage (BAL) inflammatory cells in ROCK2(+/-) mice. Compared with wild-type mice, ozone induced increases in BAL hyaluronan, a matrix protein implicated in ozone-induced AHR, were lower in ROCK1(+/-) but not ROCK2(+/-) mice. Ozone-induced increases in other inflammatory moieties reported to contribute to ozone-induced AHR (IL-17A, osteopontin, TNFalpha) were not different in wild-type vs. ROCK1(+/-) or ROCK2(+/ ) mice. We also observed a dose-dependent reduction in ozone-induced AHR after treatment with the ROCK1/ROCK2 inhibitor fasudil, even though fasudil was administered after induction of inflammation. Ozone increased pulmonary expression of ROCK2 but not ROCK1 or RhoA. A ROCK2 inhibitor, SR3677, reduced contractile forces in primary human airway smooth muscle cells, confirming a role for ROCK2 in airway smooth muscle contraction. Our results demonstrate that ozone induced AHR requires ROCK. Whereas ROCK1-dependent changes in hyaluronan may contribute to ROCK1's role in O3-induced AHR, the role of ROCK2 is downstream of inflammation, likely at the level of airway smooth muscle contraction. PMID- 26276828 TI - Impaired Quadriceps Rate of Torque Development and Knee Mechanics After Anterior Cruciate Ligament Reconstruction With Patellar Tendon Autograft. AB - BACKGROUND: Rate of torque development (RTD) measures the ability of a muscle to produce torque quickly. Decreased quadriceps RTD may impair performance of sporting tasks after surgery. Currently, little is known about variations in quadriceps RTD between anterior cruciate ligament (ACL)-reconstructed and noninjured limbs. PURPOSE: To determine the differences in RTD of the quadriceps, the rate and timing of knee extensor moment (KEM) development, and knee flexion excursion during running after ACL reconstruction with patellar tendon autograft. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: This study involved 21 patients (11 female) 6 months after ACL reconstruction with patellar tendon autograft (median [IQR]: age, 18 [16-20] years; mass, 68.18 [61.34-75] kg; height, 1.74 [1.66-1.78] m). Patients performed four 5-second maximal voluntary isometric strength trials of both limbs on an isokinetic dynamometer. RTD was calculated as the mean slope of the torque-time curve between 20% and 80% of total time to peak torque. Then, patients underwent 3-dimensional motion analysis while running on an instrumented treadmill at a self-selected running speed (mean +/- SD, 2.68 +/- 0.28 m/s). The rate of knee extensor moment (RKEM) was calculated as the mean slope of the moment curve between 10% and 30% of stance phase. Between-limb comparisons were determined with a paired t test for peak KEM, RKEM, knee flexion excursion during 10% to 30% of stance, and time to generate KEM. RESULTS: In the reconstructed limb, deficits in the peak rate of quadriceps torque development compared with the noninjured limb existed both isometrically (RTD, 257.56 vs 569.11 Nm/s; P < .001) and dynamically (RKEM, 16.47 vs 22.38 Nm/kg.m.s; P < .001). The reconstructed limb also generated a KEM later in the stance phase compared with the noninjured limb (11.37% vs 9.61% stance; P < .001) and underwent less knee flexion excursion (15.5 degrees vs 19.8 degrees ; P < .001). CONCLUSION: After ACL reconstruction with patellar tendon autograft, patients have lower RTD and RKEM in the reconstructed limb. Deviations in RTD and the timing of the KEM can change the way the knee is loaded and can potentially increase injury risk and future development of posttraumatic osteoarthritis. Rehabilitation should consider exercises designed to improve RTD and prepare the limb for the demands of sport performance. PMID- 26276829 TI - Prevention of non-communicable diseases and special causes of heart failure. PMID- 26276830 TI - CardioPulse Articles. PMID- 26276832 TI - The Transcriptional Coregulator LEUNIG_HOMOLOG Inhibits Light-Dependent Seed Germination in Arabidopsis. AB - PHYTOCHROME-INTERACTING FACTOR1 (PIF1) is a basic helix-loop-helix transcription factor that inhibits light-dependent seed germination in Arabidopsis thaliana. However, it remains unclear whether PIF1 requires other factors to regulate its direct targets. Here, we demonstrate that LEUNIG_HOMOLOG (LUH), a Groucho family transcriptional corepressor, binds to PIF1 and coregulates its targets. Not only are the transcriptional profiles of the luh and pif1 mutants remarkably similar, more than 80% of the seeds of both genotypes germinate in the dark. We show by chromatin immunoprecipitation that LUH binds a subset of PIF1 targets in a partially PIF1-dependent manner. Unexpectedly, we found LUH binds and coregulates not only PIF1-activated targets but also PIF1-repressed targets. Together, our results indicate LUH functions with PIF1 as a transcriptional coregulator to inhibit seed germination. PMID- 26276834 TI - Conserved Functions of the MATE Transporter BIG EMBRYO1 in Regulation of Lateral Organ Size and Initiation Rate. AB - Genetic networks that determine rates of organ initiation and organ size are key regulators of plant architecture. Whereas several genes that influence the timing of lateral organ initiation have been identified, the regulatory pathways in which these genes operate are poorly understood. Here, we identify a class of genes implicated in regulation of the lateral organ initiation rate. Loss-of function mutations in the MATE transporter encoded by maize (Zea mays) Big embryo 1 (Bige1) cause accelerated leaf and root initiation as well as enlargement of the embryo scutellum. BIGE1 is localized to trans-Golgi, indicating a possible role in secretion of a signaling molecule. Interestingly, phenotypes of bige1 bear striking similarity to cyp78a mutants identified in diverse plant species. We show that a CYP78A gene is upregulated in bige1 mutant embryos, suggesting a role for BIGE1 in feedback regulation of a CYP78A pathway. We demonstrate that accelerated leaf formation and early flowering phenotypes conditioned by mutants of Arabidopsis thaliana BIGE1 orthologs are complemented by maize Bige1, showing that the BIGE1 transporter has a conserved function in regulation of lateral organ initiation in plants. We propose that BIGE1 is required for transport of an intermediate or product associated with the CYP78A pathway. PMID- 26276835 TI - Taking Hormone Crosstalk to a New Level: Brassinosteroids Regulate Gibberellin Biosynthesis. PMID- 26276833 TI - The Plant Peptidome: An Expanding Repertoire of Structural Features and Biological Functions. AB - Peptides fulfill a plethora of functions in plant growth, development, and stress responses. They act as key components of cell-to-cell communication, interfere with signaling and response pathways, or display antimicrobial activity. Strikingly, both the diversity and amount of plant peptides have been largely underestimated. Most characterized plant peptides to date acting as small signaling peptides or antimicrobial peptides are derived from nonfunctional precursor proteins. However, evidence is emerging on peptides derived from a functional protein, directly translated from small open reading frames (without the involvement of a precursor) or even encoded by primary transcripts of microRNAs. These novel types of peptides further add to the complexity of the plant peptidome, even though their number is still limited and functional characterization as well as translational evidence are often controversial. Here, we provide a comprehensive overview of the reported types of plant peptides, including their described functional and structural properties. We propose a novel, unifying peptide classification system to emphasize the enormous diversity in peptide synthesis and consequent complexity of the still expanding knowledge on the plant peptidome. PMID- 26276838 TI - Thoracic endovascular repair first for extensive aortic disease: the staged hybrid approach?. AB - OBJECTIVES: Repair of extensive aortic disease carries a significant risk of death and morbidity, the most feared complication being spinal cord ischaemia. Objectives of this study are to characterize patients, describe repair methods and assess feasibility and safety of hybrid staged repair for treatment of extensive aortic disease. METHODS: From to 2001 to 2013, 22 patients underwent extensive aortic repair that included a thoracic endovascular aortic repair (TEVAR) first followed by an open completion repair extending through the visceral and infrarenal aorta for degenerative aneurysm and dissection. At the time of initial repair, all patients were deemed to be at a high risk for conventional open repair and had extensive disease. Indications for open completion included emergency failure of TEVAR (n = 3), early two-stage approach (n = 6) and delayed disease progression after TEVAR (n = 13). The median interval between stages was 6.5 months. The mean age was 56 +/- 14 years, 5 patients had connective tissue disorder and the mean maximum aortic diameter was 58 +/- 16 mm preoperatively. RESULTS: There was no death or major complication after initial TEVAR, but the operative mortality rate was 9% (n = 2) after the open procedure. One of these patients died from intraoperative myocardial infarction during emergency repair, and the other had disseminated intravascular coagulation during delayed repair for disease progression after TEVAR. Other complications included paralysis in 1 (4.5%), tracheostomy in 2 (9%) and dialysis in 1 (4.5%), and there was 1 reoperation for bleeding (4.5%). The median follow-up was 37 (range 3.3-93) months and there were no late deaths. There were four late reoperations for proximal disease progression leading to Type 1 endoleak (n = 2), Type A dissection (n = 1) and root aneurysm (n = 1). CONCLUSIONS: Use of a TEVAR-first approach in combination with a staged open repair is a safe and feasible treatment strategy for repair of extensive aortic disease. A staged hybrid approach to aortic repair in patients at high risk for total aortic replacement may limit morbidity. PMID- 26276837 TI - Activity and outcomes for aortic valve implantations performed in England and Wales since the introduction of transcatheter aortic valve implantation. AB - OBJECTIVES: The first transcatheter aortic valve implantation (TAVI) in England and Wales was performed in 2007. This study presents the subsequent national activity and outcomes for both TAVI and aortic valve replacement (AVR). METHODS: Data for all AVR and TAVI procedures between January 2006 and December 2012 in England and Wales were included. The number of procedures, patient characteristics, in-hospital and 30-day mortality, postoperative length of stay (PLOS) and survival were analysed separately for: isolated AVR; AVR + coronary artery bypass graft (CABG) surgery; AVR + other surgery and TAVI. RESULTS: The number of TAVIs increased from 66 in 2007 (0.8% of all implants) to 1186 in 2012 (10.9% of all implants). AVR activity also increased over the study period. TAVI patients were older and had a higher mean logistic EuroSCORE than all AVR groups. The 30-day mortality rates were 2.1% for isolated AVR, 3.9% for AVR + CABG, 7.7% for AVR + other surgery and 6.2% for TAVI. In-hospital mortality has significantly improved for all groups. The 5-year survival rates were 82.6% for isolated AVR, 81.7% for AVR + CABG, 74.5% for AVR + other surgery and 46.1% for TAVI. The median PLOS after TAVI was similar to that of isolated AVR but shorter than that of the other AVR groups. CONCLUSIONS: Since the introduction of TAVI, there has been an increase in both TAVI and AVR activity. TAVIs now represent over 10% of all aortic valve implants. There are distinct differences between procedural groups with respect to patient risk factors. Outcomes for all procedural groups have improved, but long-term TAVI results are required before its role in the treatment of aortic stenosis can be fully defined. PMID- 26276836 TI - Crosstalk between Two bZIP Signaling Pathways Orchestrates Salt-Induced Metabolic Reprogramming in Arabidopsis Roots. AB - Soil salinity increasingly causes crop losses worldwide. Although roots are the primary targets of salt stress, the signaling networks that facilitate metabolic reprogramming to induce stress tolerance are less understood than those in leaves. Here, a combination of transcriptomic and metabolic approaches was performed in salt-treated Arabidopsis thaliana roots, which revealed that the group S1 basic leucine zipper transcription factors bZIP1 and bZIP53 reprogram primary C- and N-metabolism. In particular, gluconeogenesis and amino acid catabolism are affected by these transcription factors. Importantly, bZIP1 expression reflects cellular stress and energy status in roots. In addition to the well-described abiotic stress response pathway initiated by the hormone abscisic acid (ABA) and executed by SnRK2 (Snf1-RELATED-PROTEIN-KINASE2) and AREB like bZIP factors, we identify a structurally related ABA-independent signaling module consisting of SnRK1s and S1 bZIPs. Crosstalk between these signaling pathways recruits particular bZIP factor combinations to establish at least four distinct gene expression patterns. Understanding this signaling network provides a framework for securing future crop productivity. PMID- 26276839 TI - Current evidence of coronary artery bypass grafting off-pump versus on-pump: a systematic review with meta-analysis of over 16,900 patients investigated in randomized controlled trials?. AB - In the present systematic review with meta-analysis, we sought to determine the current strength of evidence for or against off-pump and on-pump coronary artery bypass grafting (CABG) with regard to hard clinical end-points, graft patency and cost-effectiveness. We performed a meta-analysis of only randomized controlled trials (RCT) which reported at least one of the desired end-points including: (i) major adverse cardiac and cerebrovascular events (MACCE), (ii) all-cause mortality, (iii) myocardial infarction, (iv) cerebrovascular accident, (v) repeat revascularization, (vi) graft patency and (vii) cost-effectiveness. The pooled treatment effects [odds ratio (OR) or weighted mean difference, 95% confidence intervals (95% CIs)] were assessed using a fixed or random effects model. A total of 16 904 patients from 51 studies were identified after literature search of the major databases using a predefined keyword list. The incidence of MACCE did not differ between the groups, neither during the first 30 days (OR: 0.93; 95% CI: 0.82-1.04) nor for the longest available follow-up (OR: 1.01; 95% CI: 0.92-1.12). While the incidence of mid-term graft failure (OR: 1.37; 95% CI: 1.09-1.72) and the need for repeat revascularization (OR: 1.55; 95% CI: 1.33-1.80) was increased after off-pump surgery, on-pump surgery was associated with an increased occurrence of stroke (OR: 0.74; 95% CI: 0.58-0.95), renal impairment (OR: 0.79; 95% CI: 0.71-0.89) and mediastinitis (OR: 0.44; 95% CI: 0.31-0.62). There was no difference with regard to hard clinical end-points between on- or off-pump surgery, including myocardial infarction or mortality. The present systematic review emphasizes that both off- and on-pump surgery provide excellent and comparable results in patients requiring surgical revascularization. The choice for either strategy should take into account the individual patient profile (comorbidities, life expectancy, etc.) and importantly, the surgeon's experience in performing on- or off-pump CABG in their routine practice. PMID- 26276840 TI - Health care in the United States--basic human right or entitlement? PMID- 26276841 TI - Bilateral arterial ducts with isolated left subclavian artery in ventriculo arterial discordance, ventricular septal defect, and coarctation. PMID- 26276842 TI - Overexpression of Arabidopsis Ceramide Synthases Differentially Affects Growth, Sphingolipid Metabolism, Programmed Cell Death, and Mycotoxin Resistance. AB - Ceramide synthases catalyze an N-acyltransferase reaction using fatty acyl coenzyme A (CoA) and long-chain base (LCB) substrates to form the sphingolipid ceramide backbone and are targets for inhibition by the mycotoxin fumonisin B1 (FB1). Arabidopsis (Arabidopsis thaliana) contains three genes encoding ceramide synthases with distinct substrate specificities: LONGEVITY ASSURANCE GENE ONE HOMOLOG1 (LOH1; At3g25540)- and LOH3 (At1g19260)-encoded ceramide synthases use very-long-chain fatty acyl-CoA and trihydroxy LCB substrates, and LOH2 (At3g19260)-encoded ceramide synthase uses palmitoyl-CoA and dihydroxy LCB substrates. In this study, complementary DNAs for each gene were overexpressed to determine the role of individual isoforms in physiology and sphingolipid metabolism. Differences were observed in growth resulting from LOH1 and LOH3 overexpression compared with LOH2 overexpression. LOH1- and LOH3-overexpressing plants had enhanced biomass relative to wild-type plants, due in part to increased cell division, suggesting that enhanced synthesis of very-long-chain fatty acid/trihydroxy LCB ceramides promotes cell division and growth. Conversely, LOH2 overexpression resulted in dwarfing. LOH2 overexpression also resulted in the accumulation of sphingolipids with C16 fatty acid/dihydroxy LCB ceramides, constitutive induction of programmed cell death, and accumulation of salicylic acid, closely mimicking phenotypes observed previously in LCB C-4 hydroxylase mutants defective in trihydroxy LCB synthesis. In addition, LOH2- and LOH3-overexpressing plants acquired increased resistance to FB1, whereas LOH1 overexpressing plants showed no increase in FB1 resistance, compared with wild type plants, indicating that LOH1 ceramide synthase is most strongly inhibited by FB1. Overall, the findings described here demonstrate that overexpression of Arabidopsis ceramide synthases results in strongly divergent physiological and metabolic phenotypes, some of which have significance for improved plant performance. PMID- 26276845 TI - Everything flows: A process perspective on life. PMID- 26276843 TI - Something Old, Something New: Conserved Enzymes and the Evolution of Novelty in Plant Specialized Metabolism. AB - Plants produce hundreds of thousands of small molecules known as specialized metabolites, many of which are of economic and ecological importance. This remarkable variety is a consequence of the diversity and rapid evolution of specialized metabolic pathways. These novel biosynthetic pathways originate via gene duplication or by functional divergence of existing genes, and they subsequently evolve through selection and/or drift. Studies over the past two decades revealed that diverse specialized metabolic pathways have resulted from the incorporation of primary metabolic enzymes. We discuss examples of enzyme recruitment from primary metabolism and the variety of paths taken by duplicated primary metabolic enzymes toward integration into specialized metabolism. These examples provide insight into processes by which plant specialized metabolic pathways evolve and suggest approaches to discover enzymes of previously uncharacterized metabolic networks. PMID- 26276846 TI - Determination of 3,4-Dihydroxy Methyl Benzoate in Rat Plasma by HPLC and Its Pharmacokinetics. AB - A high-performance liquid chromatography method was established for determination of 3,4-dihydroxy methyl benzoate in rat plasma and for investigation of pharmacokinetics after intragastric administration of 3,4-dihydroxy methyl benzoate water solution. 3,4-Dihydroxy methyl benzoate and internal standard were separated on a Diamonsil(TM) C18 column (250 mm * 4.6 mm, 5 um), using a mobile phase of methanol-acetonitrile-water-glacial acetic acid (6 : 3 : 100 : 0.25, v/v/v/v), and the detection wavelength was 254 nm. The calibration curve of 3,4 dihydroxy methyl benzoate was linear in the concentration range of 0.1313-25.25 ug mL(-1). The lower limit of quantification was 0.1313 ug mL(-1), and the relative standard deviations of intra- and inter-day were <11.7%. The main pharmacokinetic parameters were as follows: Cmax (12.1 +/- 1.93) mg L(-1), Tmax (27.5 +/- 6.12) h, t1/2 (39.2 +/- 5.66) h, AUC(0->t)(0.85 +/- 0.13) g min L(-1), AUC(0->infinity) (0.88 +/- 0.14) g min L(-1), MRT (70.7 +/- 5.27) min(-1), Vd (0.32 +/- 0.04) L and CL (5.79 +/- 0.82) mL min(-1). The method is proven to be suitable for the pharmacokinetic study of 3,4-dihydroxy methyl benzoate, which offers the advantage of simplicity, sensitivity and accuracy. PMID- 26276844 TI - Living to Die and Dying to Live: The Survival Strategy behind Leaf Senescence. AB - Senescence represents the final developmental act of the leaf, during which the leaf cell is dismantled in a coordinated manner to remobilize nutrients and to secure reproductive success. The process of senescence provides the plant with phenotypic plasticity to help it adapt to adverse environmental conditions. Here, we provide a comprehensive overview of the factors and mechanisms that control the onset of senescence. We explain how the competence to senesce is established during leaf development, as depicted by the senescence window model. We also discuss the mechanisms by which phytohormones and environmental stresses control senescence as well as the impact of source-sink relationships on plant yield and stress tolerance. In addition, we discuss the role of senescence as a strategy for stress adaptation and how crop production and food quality could benefit from engineering or breeding crops with altered onset of senescence. PMID- 26276847 TI - Topiramate: A Review of Analytical Approaches for the Drug Substance, Its Impurities and Pharmaceutical Formulations. AB - An important step during the development of high-performance liquid chromatography (HPLC) methods for quantitative analysis of drugs is choosing the appropriate detector. High sensitivity, reproducibility, stability, wide linear range, compatibility with gradient elution, non-destructive detection of the analyte and response unaffected by changes in the temperature/flow are some of the ideal characteristics of a universal HPLC detector. Topiramate is an anticonvulsant drug mainly used for the treatment of different types of seizures and prophylactic treatment of migraine. Different analytical approaches to quantify topiramate by HPLC have been described because of the lack of chromophoric moieties on its structure, such as derivatization with fluorescent moieties and UV-absorbing moieties, conductivity detection, evaporative light scattering detection, refractive index detection, chemiluminescent nitrogen detection and MS detection. Some methods for the determination of topiramate by capillary electrophoresis and gas chromatography have also been published. This systematic review provides a description of the main analytical methods presented in the literature to analyze topiramate in the drug substance and in pharmaceutical formulations. Each of these methods is briefly discussed, especially considering the detector used with HPLC. In addition, this article presents a review of the data available regarding topiramate stability, degradation products and impurities. PMID- 26276848 TI - An atypical limping teenager. AB - A 13-year-old boy presented with a 5-day history of left-sided limp of gradual onset. There was no history of trauma. He developed a fever and rigours a few days before presenting to the paediatric emergency department. On examination, he was tender on palpating the left gluteal area on active mobilisation of the left hip and could not weight bear on the left leg. Pelvic X-rays and ultrasound of the left hip were normal. The blood results showed raised inflammatory markers and normal white cell count. The blood cultures were positive for Staphylococcus aureus. On day 2, a left hip MRI was performed as well as CT-guided drainage. Diagnosis of left sacroiliac septic arthritis was made. After an initial lack of improvement under intravenous ceftriaxone, a drain was inserted and left in situ for 8 days with double intravenous antibiotic therapy instituted. The patient made a full recovery. PMID- 26276849 TI - Cornelia de Lange syndrome due to mosaic NIPBL mutation: antenatal presentation with sacrococcygeal teratoma. AB - A male infant at 36 weeks gestation was born by section. At 20 weeks of gestation, congenital diaphragmatic hernia and sacrococcygeal teratoma had been seen on ultrasound. At birth, the infant had features suggestive of Cornelia de Lange syndrome (CdLS). He remained hypoxic despite aggressive ventilatory manoeuvres and was palliated. At postmortem, the lungs were hypoplastic. In CdLS, mutations in NIPBL are found in around 50% of cases. Mutation analysis, including multiplex ligation dependent probe amplification of the NIPBL gene from the DNA extracted from peripheral blood lymphocytes was negative, but microarray comparative genomic hybridisation on DNA from skin fibroblast showed a 0.13Mb deletion on chromosome 5p13. The deleted region includes exons 42-47 of the NIPBL gene. It is important to perform NIBPL mutation analysis on DNA from more than one tissue when testing for CdLS. PMID- 26276850 TI - Renal cell carcinoma presenting as an upper gastrointestinal bleeding. AB - An 80-year-old man presented with melaena and anaemia of 1 week duration. This was associated with shortness of breath and an indigestion-type pain for the preceding 8 weeks. General physical examination revealed epigastric tenderness, but an otherwise soft abdomen with no organomegaly. The patient had a gastroscopy, showing a polypoidal lesion in the second part of duodenum (D2) as the bleeding point, which was managed with epinephrine injection and endoclips. This was followed by CT of the abdomen, revealing a lobulated 8 cm mass arising from the lower pole of the right kidney and invading the duodenum. The case report aims to acknowledge the possibility of direct duodenal involvement in renal cell carcinoma, which is a rare occurrence. PMID- 26276851 TI - A case of a slightly symptomatic exfoliative oesophagitis. PMID- 26276852 TI - ST-segment elevation myocardial infarction with anomalous right coronary artery originating from the mid-left anterior descending artery. PMID- 26276853 TI - A positive cooperativity binding model between Ly49 natural killer cell receptors and the viral immunoevasin m157. KINETIC AND THERMODYNAMIC STUDIES. PMID- 26276854 TI - c-Myc programs fatty acid metabolism and dictates acetyl-CoA abundance and fate. PMID- 26276855 TI - Membrane and integrative nuclear fibroblastic growth factor receptor (FGFR) regulation of FGF-23. PMID- 26276856 TI - Heat shock protein 70 interacts with nucleolin and inhibits its cleavage, downregulation and apoptosis induced by hydrogen peroxide in myocytes. PMID- 26276857 TI - The troponin T isoform shift may constitute a protective compensatory mechanism in hypertrophic cardiomyopathy. PMID- 26276858 TI - TcJAMYC: a bHLH transcription factor that activates paclitaxel biosynthetic pathway genes in yew. PMID- 26276859 TI - Function and Structure of the RWD Domain. PMID- 26276861 TI - Insects modify their behaviour depending on the feedback sensor used when walking on a trackball in virtual reality. AB - When using virtual-reality paradigms to study animal behaviour, careful attention must be paid to how the animal's actions are detected. This is particularly relevant in closed-loop experiments where the animal interacts with a stimulus. Many different sensor types have been used to measure aspects of behaviour, and although some sensors may be more accurate than others, few studies have examined whether, and how, such differences affect an animal's behaviour in a closed-loop experiment. To investigate this issue, we conducted experiments with tethered honeybees walking on an air-supported trackball and fixating a visual object in closed-loop. Bees walked faster and along straighter paths when the motion of the trackball was measured in the classical fashion - using optical motion sensors repurposed from computer mice - than when measured more accurately using a computer vision algorithm called 'FicTrac'. When computer mouse sensors were used to measure bees' behaviour, the bees modified their behaviour and achieved improved control of the stimulus. This behavioural change appears to be a response to a systematic error in the computer mouse sensor that reduces the sensitivity of this sensor system under certain conditions. Although the large perceived inertia and mass of the trackball relative to the honeybee is a limitation of tethered walking paradigms, observing differences depending on the sensor system used to measure bee behaviour was not expected. This study suggests that bees are capable of fine-tuning their motor control to improve the outcome of the task they are performing. Further, our findings show that caution is required when designing virtual-reality experiments, as animals can potentially respond to the artificial scenario in unexpected and unintended ways. PMID- 26276860 TI - Control of Trx1 redox state modulates protection against methyl methanesulfonate induced DNA damage via stabilization of p21. AB - Thioredoxin 1 (Trx1) is known to play an important role in protecting against cell death. However, the mechanism for control of Trx1 in cell death resulting from DNA damage has not been fully investigated. In this study, we used the DNA damaging agent methyl methanesulfonate (MMS) to investigate the protective effects of Trx1 against DNA damage and cell death in HEK293 cells. We found that MMS application caused dose-dependent changes in the Trx1 redox state determined by redox western blotting. At lower concentrations, both reduced and oxidized Trx1 were observed, whereas the reduced band was fully oxidized at the higher concentration. Trx1 overexpression and small interfering RNA knockdown in cells revealed that reduced Trx1 after exposure to lower doses of MMS attenuated DNA damage, assessed by comet assay, and level of the DNA-damage marker histone gamma H2AX, possibly through scavenging intracellular ROS and an increase in p21 protein level via enhancing its stability. However, oxidized Trx1 lost its protective ability to DNA damage in response to higher concentration of MMS. Corresponding to the redox state control of Trx1, cell death induced by different dose of MMS was also found, by inhibiting phosphorylations of p38 and 4E-BP1. These results indicate that reduced Trx1 plays important protective roles against MMS-induced DNA damage and cell death, suggesting that cell protection is regulated by the intracellular redox state. Control of the redox state of Trx1 and its regulating proteins may offer a novel therapeutic strategy for the control of cancer. PMID- 26276862 TI - Circadian modulation of learning ability in a disease vector insect, Rhodnius prolixus. AB - Despite the drastic consequences it may have on the transmission of parasites, the ability of disease vectors to learn and retain information has just begun to be characterised. The kissing bug Rhodnius prolixus, a vector of Chagas disease, is an excellent model, particularly because conditioning the proboscis extension response (PER) constitutes a valuable paradigm to study their cognitive abilities under carefully controlled conditions. Another characteristic of these bugs is the temporal organisation of their different activities in a bimodal endogenous daily rhythm. This offers the opportunity to address the implication of the circadian system in learning and memory. Using aversive conditioning of the PER, we tested whether the ability of kissing bugs to learn and remember information varies during the day. We found that bugs perform well during the night, but not during the day: their ability to acquire information - but not their ability to retrieve it - is modulated by time. When the bugs were kept under constant conditions in order to analyse the origin of this rhythm, the rhythm continued to free run, showing its endogenous and truly circadian nature. These results are the first to evince the effect of the circadian system on the learning abilities of disease vectors and one of the few in insects in general. PMID- 26276863 TI - Mode-dependent control of human walking and running as revealed by split-belt locomotor adaptation. AB - Here, we investigate the association of neural control between walking and running, and in particular, how these two gait modes at different velocities are controlled by the central nervous system. The subjects were fully adapted by acquiring modified motor patterns to either walk or run on a split-belt treadmill driven in split mode (asymmetry in the velocities of two belts at 1.0 and 2.0 m s(-1)). Subsequently, we tested how the adaptation affected walking and running at three different velocities in the tied mode (equal belt velocities). At 0.75 m s(-1), we found a preference to walk, at 1.50 m s(-1), there was a preference to both walk and run, and at a velocity of 2.25 m s(-1) there was a preference to run. Both walking and running on the split belt resulted in the emergence of a significant aftereffect (asymmetrical movement) at all of the velocities tested when walking after adapting to walk and running after adapting to run. However, for contrasting modes (i.e. running after adapting to walk and walking after adapting to run), such aftereffects were far less evident at all velocities; thus showing only limited transfer across gait modes. The results demonstrate a clear mode dependency in the neural control of human walking and running. In addition, only for walking, was there a degree of velocity dependency. PMID- 26276864 TI - Double-network gels and the toughness of terrestrial slug glue. AB - The terrestrial slug Arion subfuscus produces a defensive secretion that is sticky and tough, despite being a dilute gel. It is unusual in having high stiffness for a gel, yet retaining the high extensibility typical of mucus. In tensile tests, it sustains an average peak stress of 101 kPa, and fails at an average strain of 9.5. This gives the gel toughness; it requires much greater strain energy to fracture than most gels. This toughness may arise from a double network type mechanism. In this mechanism, two separate, interpenetrating networks of polymers with different properties combine to give toughness that can be several orders of magnitude greater than either network individually. Native gel electrophoresis suggests that A. subfuscus glue consists of two networks: a network of negatively charged proteins ranging in Mr from 40*10(3) to 220*10(3) that can be dissociated by hydroxylamine and a network of heparan sulfate-like proteoglycans. The two networks are not tightly linked, though proteins of Mr 40*10(3) and 165*10(3) may associate with the carbohydrates. Targeted disruption of either network separately, using enzymatic hydrolysis, disulfide bond breakage or imine bond disruption completely disrupted the glue, resulting in no measurable toughness. Thus, the two networks separately provide little toughness, but together they work synergistically to create a tough material, as predicted in the double-network mechanism. PMID- 26276865 TI - Increasing cyclic electron flow is related to Na+ sequestration into vacuoles for salt tolerance in soybean. AB - In land plants, the NAD(P)H dehydrogenase (NDH) complex reduces plastoquinones and drives cyclic electron flow (CEF) around PSI. It also produces extra ATP for photosynthesis and improves plant fitness under conditions of abiotic environmental stress. To elucidate the role of CEF in salt tolerance of the photosynthetic apparatus, Na(+) concentration, chlorophyll fluorescence, and expression of NDH B and H subunits, as well as of genes related to cellular and vacuolar Na(+) transport, were monitored. The salt-tolerant Glycine max (soybean) variety S111-9 exhibited much higher CEF activity and ATP accumulation in light than did the salt-sensitive variety Melrose, but similar leaf Na(+) concentrations under salt stress. In S111-9 plants, ndhB and ndhH were highly up regulated under salt stress and their corresponding proteins were maintained at high levels or increased significantly. Under salt stress, S111-9 plants accumulated Na(+) in the vacuole, but Melrose plants accumulated Na(+) in the chloroplast. Compared with Melrose, S111-9 plants also showed higher expression of some genes associated with Na(+) transport into the vacuole and/or cell, such as genes encoding components of the CBL10 (calcineurin B-like protein 10)-CIPK24 (CBL-interacting protein kinase 24)-NHX (Na(+)/H(+) antiporter) and CBL4 (calcineurin B-like protein 4)-CIPK24-SOS1 (salt overly sensitive 1) complexes. Based on the findings, it is proposed that enhanced NDH-dependent CEF supplies extra ATP used to sequester Na(+) in the vacuole. This reveals an important mechanism for salt tolerance in soybean and provides new insights into plant resistance to salt stress. PMID- 26276866 TI - Hormone-mediated growth dynamics of the barley pericarp as revealed by magnetic resonance imaging and transcript profiling. AB - The shape of the maternal pericarp affects cereal grain mass and yield. Pericarp growth was analysed by magnetic resonance imaging (MRI), revealing topological maps of mobile water in developing pericarp of barley (Hordeum vulgare) and displaying tissue regions actively elongating in specific temporal-spatial patterns. Correlation analysis of MRI signals and growth rates reveals that growth in length is mediated by dorsal and also lateral rather than ventral regions. Growth in thickness is related to ventral regions. Switching from dorsal to ventral growth is associated with differential expression of axial regulators of the HD-ZipIII and Kanadi/Ettin types, and NPH3 photoreceptors, suggesting light-mediated auxin re-distribution. Auxin increases with the highest levels in the basal pericarp at 6 days after fertilization (DAF), together with transcriptionally up-regulated auxin transport and signalling. Gibberellin biosynthesis is transcriptionally up-regulated only later, and levels of bioactive gibberellins increase from 7 to 13 DAF, with higher levels in ventral than dorsal regions. Differential gene expression related to cell expansion indicates genes related to apoplast acidification, wall relaxation, sugar cleavage, water transport, and cell wall biosynthesis. Candidate genes potentially involved in pericarp extension are distinguished by their temporal expression, representing potential isoforms responsible for dorsal-mediated early growth in length or ventral-mediated late growth in thickness. PMID- 26276867 TI - Mutation of SPOTTED LEAF3 (SPL3) impairs abscisic acid-responsive signalling and delays leaf senescence in rice. AB - Lesion mimic mutants commonly display spontaneous cell death in pre-senescent green leaves under normal conditions, without pathogen attack. Despite molecular and phenotypic characterization of several lesion mimic mutants, the mechanisms of the spontaneous formation of cell death lesions remain largely unknown. Here, the rice lesion mimic mutant spotted leaf3 (spl3) was examined. When grown under a light/dark cycle, the spl3 mutant appeared similar to wild-type at early developmental stages, but lesions gradually appeared in the mature leaves close to heading stage. By contrast, in spl3 mutants grown under continuous light, severe cell death lesions formed in developing leaves, even at the seedling stage. Histochemical analysis showed that hydrogen peroxide accumulated in the mutant, likely causing the cell death phenotype. By map-based cloning and complementation, it was shown that a 1-bp deletion in the first exon of Oryza sativa Mitogen-Activated Protein Kinase Kinase Kinase1 (OsMAPKKK1)/OsEDR1/OsACDR1 causes the spl3 mutant phenotype. The spl3 mutant was found to be insensitive to abscisic acid (ABA), showing normal root growth in ABA-containing media and delayed leaf yellowing during dark-induced and natural senescence. Expression of ABA signalling-associated genes was also less responsive to ABA treatment in the mutant. Furthermore, the spl3 mutant had lower transcript levels and activities of catalases, which scavenge hydrogen peroxide, probably due to impairment of ABA responsive signalling. Finally, a possible molecular mechanism of lesion formation in the mature leaves of spl3 mutant is discussed. PMID- 26276868 TI - Melatonin biosynthesis requires N-acetylserotonin methyltransferase activity of caffeic acid O-methyltransferase in rice. AB - Caffeic acid O-methyltransferase (COMT) methylates N-acetylserotonin into melatonin; that is, it has N-acetylserotonin O-methyltransferase (ASMT) activity. The ASMT activity of COMT was first detected in Arabidopsis thaliana COMT (AtCOMT). To confirm the involvement of COMT on melatonin synthesis in other plant species, the ASMT activity of a COMT from rice (Oryza sativa) (OsCOMT) was evaluated. Purified recombinant OsCOMT protein from Escherichia coli was used to validate the high ASMT activity of OsCOMT, similar to that of AtCOMT. The K m and V max values for the ASMT activity of OsCOMT were 243 uM and 2400 pmol min(-1) mg protein(-1), which were similar to those of AtCOMT. Similar to AtCOMT, OsCOMT was localized in the cytoplasm. In vitro ASMT activity was significantly inhibited by either caffeic acid or quercetin in a dose-dependent manner. Analogously, in vivo production of melatonin was significantly inhibited by quercetin in 4-week-old detached rice leaves. Lastly, the transgenic rice plants overexpressing rice COMT showed an increase in melatonin levels whereas transgenic rice plants suppressing the rice COMT had a significant decrease on melatonin levels, suggestive of the direct role of COMT in melatonin biosynthesis in plants. PMID- 26276869 TI - Cutting Edge: miR-17-92 Is Required for Both CD4 Th1 and T Follicular Helper Cell Responses during Viral Infection. AB - Viral infections induce the differentiation of naive CD4 T cells into two distinct lineages, Th1 cells and T follicular helper (TFH) cells. Two recent studies demonstrated that the microRNA cluster miR-17-92 selectively promotes CD4 TFH responses. However, we show in this study that miR-17-92 expression is required for the clonal expansion of both virus-specific Th1 and TFH cells. Upon viral infection, miR-17-92-deficient CD4 T cells showed impaired clonal expansion and subsequent memory formation. Although miR-17-92 deficiency impaired the clonal expansion of both Th1 and TFH cells, the expansion of Th1 cells was more affected. Overexpression of miR-17-92 in CD4 T cells resulted in increased expansion of both virus-specific Th1 and TFH cells but selectively enhanced the Th1 response. Taken together, our data suggest that miR-17-92 is necessary for both Th1 and TFH cells to respond efficiently to viral infections and that the Th1 response is more sensitive to the level of miR-17-92 expression. PMID- 26276870 TI - Priming of Human Resting NK Cells by Autologous M1 Macrophages via the Engagement of IL-1beta, IFN-beta, and IL-15 Pathways. AB - The cross talk between NK cells and macrophages is emerging as a major line of defense against microbial infections and tumors. This study reveals a complex network of soluble mediators and cell-to-cell interactions allowing human classically activated (M1) macrophages, but not resting (M0) or alternatively activated (M2) macrophages, to prime resting autologous NK cells. In this article, we show that M1 increase NK cell cytotoxicity by IL-23 and IFN-beta dependent upregulation of NKG2D, IL-1beta-dependent upregulation of NKp44, and trans-presentation of IL-15. Moreover, both IFN-beta-dependent cis-presentation of IL-15 on NK cells and engagement of the 2B4-CD48 pathway are used by M1 to trigger NK cell production of IFN-gamma. The disclosure of these synergic cellular mechanisms regulating the M1-NK cell cross talk provides novel insights to better understand the role of innate immune responses in the physiopathology of tumor biology and microbial infections. PMID- 26276871 TI - IRF4 Is a Critical Gene in Retinoic Acid-Mediated Plasma Cell Formation and Is Deregulated in Common Variable Immunodeficiency-Derived B Cells. AB - In the present study, we aimed at identifying the mechanisms whereby the vitamin A metabolite all-trans retinoic acid (RA) promotes the formation of plasma cells upon stimulation of B cells via the innate immunity receptors TLR9 and RP105. Most often, differentiation of B cells involves the sequential events of class switch recombination and somatic hypermutations characteristic of germinal center reactions, followed by plasma cell formation. By studying the regulatory networks known to drive these reactions, we revealed that RA enhances the expression of the plasma cell-generating transcription factors IFN regulatory factor (IRF)4 and Blimp1, and paradoxically also activation-induced deaminase (AID) involved in somatic hypermutations/class switch recombination, in primary human B cells. IRF4 was identified as a particularly important protein involved in the RA-mediated production of IgG in TLR9/RP105-stimulated B cells. Based on kinetic studies, we present a model suggesting that the initial induction of IRF4 by RA favors AID expression. According to this model, the higher level of IRF4 that eventually arises results in sustained elevated levels of Blimp1. Regarded as a master regulator of plasma cell development, Blimp1 will in turn suppress AID expression and drive the formation of IgG-secreting plasma cells. Notably, we demonstrated IRF4 to be deregulated in B cells from common variable immunodeficiency patients, contributing to the observed aberrant expression of AID in these patients. Taken together, the present study both provides new insight into the mechanisms whereby RA induces differentiation of B cells and identifies IRF4 as a key to understand the defective functions of B cells in common variable immunodeficiency patients. PMID- 26276872 TI - 1,25(OH)2D3 Promotes the Efficacy of CD28 Costimulation Blockade by Abatacept. AB - Inhibition of the CD28:CD80/CD86 T cell costimulatory pathway has emerged as an effective strategy for the treatment of T cell-mediated inflammatory diseases. However, patient responses to CD28-ligand blockade by abatacept (CTLA-4-Ig) in conditions such as rheumatoid arthritis are variable and often suboptimal. In this study, we show that the extent to which abatacept suppresses T cell activation is influenced by the strength of TCR stimulation, with high-strength TCR stimulation being associated with relative abatacept insensitivity. Accordingly, cyclosporin A, an inhibitor of T cell stimulation via the TCR, synergized with abatacept to inhibit T cell activation. We also observed that 1,25-dihydroxyvitamin D3 enhanced the inhibition of T cell activation by abatacept, strongly inhibiting T cell activation driven by cross-linked anti-CD3, but with no effect upon anti-CD28 driven stimulation. Thus, like cyclosporin A, 1,25-dihydroxyvitamin D3 inhibits TCR-driven activation, thereby promoting abatacept sensitivity. Vitamin D3 supplementation may therefore be a useful adjunct for the treatment of conditions such as rheumatoid arthritis in combination with abatacept to promote the efficacy of treatment. PMID- 26276873 TI - Lipoxin A4 Attenuates Constitutive and TGF-beta1-Dependent Profibrotic Activity in Human Lung Myofibroblasts. AB - Idiopathic pulmonary fibrosis (IPF) is a common, progressive, and invariably lethal interstitial lung disease with no effective therapy. The key cell driving the development of fibrosis is the myofibroblast. Lipoxin A4 (LXA4) is an anti inflammatory lipid, important in the resolution of inflammation, and it has potential antifibrotic activity. However, the effects of LXA4 on primary human lung myofibroblasts (HLMFs) have not previously been investigated. Therefore, the aim of this study was to examine the effects of LXA4 on TGF-beta1-dependent responses in IPF- and nonfibrotic control (NFC)-derived HLMFs. HLMFs were isolated from IPF and NFC patients and grown in vitro. The effects of LXA4 on HLMF proliferation, collagen secretion, alpha-smooth muscle actin (alphaSMA) expression, and Smad2/3 activation were examined constitutively and following TGF beta1 stimulation. The LXA4 receptor (ALXR) was expressed in both NFC- and IPF derived HLMFs. LXA4 (10(-10) and 10(-8) mol) reduced constitutive alphaSMA expression, actin stress fiber formation, contraction, and nuclear Smad2/3, indicating regression from a myofibroblast to fibroblast phenotype. LXA4 also significantly inhibited FBS-dependent proliferation and TGF-beta1-dependent collagen secretion, alphaSMA expression, and Smad2/3 nuclear translocation in IPF derived HLMFs. LXA4 did not inhibit Smad2/3 phosphorylation. In summary, LXA4 attenuated profibrotic HLMF activity and promoted HLMF regression to a quiescent fibroblast phenotype. LXA4 or its stable analogs delivered by aerosol may offer a novel approach to the treatment of IPF. PMID- 26276874 TI - DNA Methylation Regulates the Differential Expression of CX3CR1 on Human IL 7Ralphalow and IL-7Ralphahigh Effector Memory CD8+ T Cells with Distinct Migratory Capacities to the Fractalkine. AB - DNA methylation is an epigenetic mechanism that modulates gene expression in mammalian cells including T cells. Memory T cells are heterogeneous populations. Human effector memory (EM) CD8(+) T cells in peripheral blood contain two cell subsets with distinct traits that express low and high levels of the IL-7Ralpha. However, epigenetic mechanisms involved in defining such cellular traits are largely unknown. In this study, we use genome-wide DNA methylation and individual gene expression to show the possible role of DNA methylation in conferring distinct traits of chemotaxis and inflammatory responses in human IL-7Ralpha(low) and IL-7Ralpha(high) EM CD8(+) T cells. In particular, IL-7Ralpha(low) EM CD8(+) T cells had increased expression of CX3CR1 along with decreased DNA methylation in the CX3CR1 gene promoter compared with IL-7Ralpha(high) EM CD8(+) T cells. Altering the DNA methylation status of the CX3CR1 gene promoter changed its activity and gene expression. IL-7Ralpha(low) EM CD8(+) T cells had an increased migratory capacity to the CX3CR1 ligand fractalkine compared with IL 7Ralpha(high) EM CD8(+) T cells, suggesting an important biological outcome of the differential expression of CX3CR1. Moreover, IL-7Ralpha(low) EM CD8(+) T cells induced fractalkine expression on endothelial cells by producing IFN-gamma and TNF-alpha, forming an autocrine amplification loop. Overall, our study shows the role of DNA methylation in generating unique cellular traits in human IL 7Ralpha(low) and IL-7Ralpha(high) EM CD8(+) T cells, including differential expression of CX3CR1, as well as potential biological implications of this differential expression. PMID- 26276875 TI - Cutting Edge: Hematopoietic Stem Cell Expansion and Common Lymphoid Progenitor Depletion Require Hematopoietic-Derived, Cell-Autonomous TLR4 in a Model of Chronic Endotoxin. AB - Hematopoietic stem and progenitors cells (HSPCs) are activated through TLR4 in vitro. However, it remains unclear whether in vivo TLR4 sensing by HSPCs occurs directly or via other cell intermediates. In this study, we examined the cellular mechanisms underlying murine hematopoietic stem cell (HSC) expansion and common lymphoid progenitor (CLP) depletion in a model of chronic low-dose LPS. Using adoptive-transfer approaches, we show that HSC and CLP sensitivity to chronic LPS depends on hematopoietic-derived, cell subset-autonomous TLR4. Like murine progenitors, human HSPCs are activated by TLR4 in vitro. Using humanized mice, a preclinical model relevant to human physiology, we show that persistent endotoxin increases the frequency of Ki-67(+) HSCs and severely depletes CLPs and B precursors. Together, our findings show that murine HSPCs directly respond to endotoxin in vivo and that persistent LPS, a feature of several diseases of global health significance, impairs human lymphopoiesis. PMID- 26276882 TI - Long-term persistence of multidrug-resistant Enterobacteriaceae after travel. PMID- 26276877 TI - Cutting Edge: AhR Is a Molecular Target of Calcitriol in Human T Cells. AB - The immunoregulatory functions of vitamin D have been well documented in various immunological disorders, including multiple sclerosis, arthritis, and asthma. IL 10 is considered a chief effector molecule that promotes the vitamin D-induced immunosuppressive states of T cells and accessory cells. In this article, we demonstrate that the active form of vitamin D, 1,25-dihydroxyvitamin D3 (calcitriol), has a profound inhibitory effect on the development of human Th9, a CD4 T cell subset that is highly associated with asthma, in an IL-10-independent manner. Our data show that calcitriol represses the expression of BATF, a transcription factor essential for Th9, via suppressing the expression of aryl hydrocarbon receptor, without an increase in IL-10. The data show a novel link between vitamin D and two key transcription factors involved in T cell differentiation. PMID- 26276883 TI - Reply to Collignon and Kennedy. PMID- 26276876 TI - IL-3 Maintains Activation of the p90S6K/RPS6 Pathway and Increases Translation in Human Eosinophils. AB - IL-5 is a major therapeutic target to reduce eosinophilia. However, all of the eosinophil-activating cytokines, such as IL-5, IL-3, and GM-CSF, are typically present in atopic diseases, including allergic asthma. As a result of the functional redundancy of these three cytokines on eosinophils and the loss of IL 5R on airway eosinophils, it is important to take IL-3 and GM-CSF into account to efficiently reduce tissue eosinophil functions. Moreover, these three cytokines signal through a common beta-chain receptor but yet differentially affect protein production in eosinophils. Notably, the increased ability of IL-3 to induce the production of proteins, such as semaphorin-7A, without affecting mRNA levels suggests a unique influence of IL-3 on translation. The purpose of this study was to identify the mechanisms by which IL-3 distinctively affects eosinophil function compared with IL-5 and GM-CSF, with a focus on protein translation. Peripheral blood eosinophils were used to study intracellular signaling and protein translation in cells activated with IL-3, GM-CSF, or IL-5. We establish that, unlike GM-CSF or IL-5, IL-3 triggers prolonged signaling through activation of ribosomal protein S6 (RPS6) and the upstream kinase 90-kDa ribosomal S6 kinase (p90S6K). Blockade of p90S6K activation inhibited phosphorylation of RPS6 and IL 3-enhanced semaphorin-7A translation. Furthermore, in an allergen-challenged environment, in vivo phosphorylation of RPS6 and p90S6K was enhanced in human airway compared with circulating eosinophils. Our findings provide new insights into the mechanisms underlying differential activation of eosinophils by IL-3, GM CSF, and IL-5. These observations identify IL-3 and its downstream intracellular signals as novel targets that should be considered to modulate eosinophil functions. PMID- 26276884 TI - Time Course of Atrial Fibrillation in Patients With Congenital Heart Defects. AB - BACKGROUND: The incidence of atrial fibrillation (AF) is rising in the aging patients with congenital heart defects (CHD). However, studies reporting on AF in patients with CHD are scarce. The aim of this multicenter study was to examine in a large cohort of patients with a variety of CHD: (1) the age of onset and initial treatment of AF, coexistence of atrial tachyarrhythmia and (2) progression of paroxysmal to (long-standing) persistent/permanent AF during long term follow-up. METHODS AND RESULTS: Patients (n=199) with 15 different CHD and documented AF episodes were studied. AF developed at 49+/-17 years. Regular atrial tachycardia (AT) coexisting with AF occurred in 65 (33%) patients; 65% initially presented with regular AT. At the end of a follow-up period of 5 (0-24) years, the ECG showed AF in 81 patients (41%). In a subgroup of 114 patients, deterioration from paroxysm of AF to (long-standing) persistent/permanent AF was observed in 29 patients (26%) after only 3 (0-18) years of the first AF episode. Cerebrovascular accidents/transient ischemic attacks occurred in 26 patients (13%), although a substantial number (n=16) occurred before the first documented AF episode. CONCLUSIONS: Age at development of AF in patients with CHD is relatively young compared with the patients without CHD. Coexistence of episodes of AF and regular AT occurred in a considerable number of patients; most of them initially presented with regular AT. The fast and frequent progression from paroxysmal to (long-standing) persistent or permanent AF episodes justifies close follow-up and early, aggressive therapy of both AT and AF. PMID- 26276885 TI - Functional Analysis of a Carotid Intima-Media Thickness Locus Implicates BCAR1 and Suggests a Causal Variant. AB - BACKGROUND: Carotid intima-media thickness (IMT) is a marker of subclinical atherosclerosis that can predict cardiovascular disease events over traditional risk factors. This study examined the BCAR1-CFDP1-TMEM170A locus on chromosome 16, associated with carotid IMT and coronary artery disease in the IMT and IMT Progression as Predictors of Vascular Events (IMPROVE) cohort, to identify the functional variant. METHODS AND RESULTS: In analysis of the locus lead single nucleotide polymorphism (SNP; rs4888378, intronic in CFDP1) in Progressione della Lesione Intimale Carotidea (PLIC), the protective AA genotype was associated with slower IMT progression in women (P=0.04) but not in men. Meta-analysis of 5 cohort studies also supported a protective effect of the A allele on common carotid IMT in women only (women: beta=-0.0047, P=1.63 * 10(-4); men: beta= 0.0029, P=0.0678). Two hundred fourteen noncoding variants in strong linkage disequilibrium (r(2) >= 0.8) with rs4888378 were identified from 1000 Genome Project. ENCODE regulatory chromatin marks were used to create a shortlist of 6 possible regulatory variants. Electrophoretic mobility shift assays on the shortlist detected allele-specific protein binding to the lead SNP rs4888378; multiplexed competitor electrophoretic mobility shift assays implicated FOXA as the protein. Luciferase reporter assays on rs4888378 showed a significant 35% to 92% (P=0.0057; P=4.0 * 10(-22)) decrease in gene expression with the A allele. Expression quantitative trait loci analysis confirmed previously reported associations of rs4888378 with BCAR1 in vascular tissues. CONCLUSIONS: Molecular studies suggest the lead SNP as a potentially causal SNP at the BCAR1-CFDP1 TMEM170A locus, and expression quantitative trait loci studies implicate BCAR1 as the causal gene. This variant showed stronger effects on common carotid IMT in women, raising questions about the mechanism of the causal SNP on atherosclerosis. PMID- 26276887 TI - Risk of Cardiomyopathy in Younger Persons With a Family History of Death from Cardiomyopathy: A Nationwide Family Study in a Cohort of 3.9 Million Persons. AB - BACKGROUND: Recommendations for presymptomatic screening of relatives of cardiomyopathy patients are based on findings from tertiary centers. Cardiomyopathy inheritance patterns are fairly well understood, but how cardiomyopathy in younger persons (<50 years) aggregates in families at the population level is unclear. In a nationwide cohort, we examined the risk of cardiomyopathy by family history of premature death (<60 years) from cardiomyopathy. METHODS AND RESULTS: By linking Danish national register data, we constructed a cohort of 3.9 million persons born from 1950 to 2008. We ascertained family history of premature (<60 years) death from cardiomyopathy or other conditions, and cohort members were followed from 1977 to 2008 for cardiomyopathy diagnosed at <50 years. We identified 3890 cardiomyopathies in 89 million person-years of follow-up. Using Poisson regression, we estimated incidence rate ratios for cardiomyopathy by family history of premature death. Premature cardiomyopathy deaths in first- and second-degree relatives were associated with 29- and 6-fold increases in the rate of cardiomyopathy, respectively. If the first-degree relative died aged <35 years, the rate of cardiomyopathy increased 100-fold; given >=2 premature deaths in first-degree relatives, the rate increased more than 400-fold. In contrast, a family history of premature death from other cardiac or noncardiac conditions increased the rate of cardiomyopathy 3-fold at most. CONCLUSIONS: A family history of premature cardiomyopathy death was associated with an increase in risk of cardiomyopathy ranging from 6- to 400-fold, depending on age, kinship, gender and number of affected family members. Our general population-based results support recommendations for presymptomatic screening of relatives of cardiomyopathy patients. PMID- 26276886 TI - Elevated Plasma Marinobufagenin, An Endogenous Cardiotonic Steroid, Is Associated With Right Ventricular Dysfunction and Nitrative Stress in Heart Failure. AB - BACKGROUND: Plasma levels of cardiotonic steroids are elevated in volume-expanded states, such as chronic kidney disease, but the role of these natriuretic hormones in subjects with heart failure (HF) is unclear. We sought to determine the prognostic role of the cardiotonic steroids marinobufagenin (MBG) in HF, particularly in relation to long-term outcomes. METHODS AND RESULTS: We first measured plasma MBG levels and performed comprehensive clinical, laboratory, and echocardiographic assessment in 245 patients with HF. All-cause mortality, cardiac transplantation, and HF hospitalization were tracked for 5 years. In our study cohort, median (interquartile range) MBG was 583 (383-812) pM. Higher MBG was associated with higher myeloperoxidase (r=0.42, P<0.0001), B-type natriuretic peptide (r=0.25, P=0.001), and asymmetrical dimethylarginine (r=0.32, P<0.001). Elevated levels of MBG were associated with measures of worse right ventricular function (RV s', r=-0.39, P<0.0001) and predicted increased risk of adverse clinical outcomes (MBG>=574 pmol/L: hazard ratio 1.58 [1.10-2.31], P=0.014) even after adjustment for age, sex, diabetes mellitus, and ischemic pathogenesis. In mice, a left anterior descending coronary artery ligation model of HF lead to increases in MBG, whereas infusion of MBG into mice for 4 weeks lead to significant increases in myeloperoxidase, asymmetrical dimethylarginine, and cardiac fibrosis. CONCLUSIONS: In the setting of HF, elevated plasma levels of MBG are associated with right ventricular dysfunction and predict worse long-term clinical outcomes in multivariable models adjusting for established clinical and biochemical risk factors. Infusion of MBG seems to directly contribute to increased nitrative stress and cardiac fibrosis. PMID- 26276888 TI - A Critical Need for Clinical Context in the Genomic Era. PMID- 26276889 TI - Positron Emission Tomography/Computed Tomography Imaging in Device Infective Endocarditis: Ready for Prime Time. PMID- 26276890 TI - Improving the Diagnosis of Infective Endocarditis in Prosthetic Valves and Intracardiac Devices With 18F-Fluordeoxyglucose Positron Emission Tomography/Computed Tomography Angiography: Initial Results at an Infective Endocarditis Referral Center. AB - BACKGROUND: The diagnosis of infective endocarditis (IE) in prosthetic valves and intracardiac devices is challenging because both the modified Duke criteria (DC) and echocardiography have limitations in this population. The added value of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) and (18)F-FDG PET/CT angiography (PET/CTA) was evaluated in this complex scenario at a referral center with a multidisciplinary IE unit. METHODS AND RESULTS: Ninety-two patients admitted to our hospital with suspected prosthetic valve or cardiac device IE between November 2012 and November 2014 were prospectively included. All patients underwent echocardiography and PET/CT, and 76 had cardiac CTA. PET/CT and echocardiography findings were evaluated and compared, with concordant results in 54% of cases (kappa=0.23). Initial diagnoses with DC at admission, PET/CT, and DC+PET/CT were compared with the final diagnostic consensus reached by the IE Unit. DC+PET/CT enabled reclassification of 90% of cases initially classified as possible IE with DC and provided a conclusive diagnosis (definite/rejected) in 95% of cases. Sensitivity, specificity, and positive and negative predictive values were 52%, 94.7%, 92.9%, and 59.7% for DC; 87%, 92.1%, 93.6%, and 84.3% for PET/CT; and 90.7%, 89.5%, 92%, and 87.9% for DC+PET/CT. Use of PET/CTA yielded even better diagnostic performance values than PET/nonenhanced CT (91%, 90.6%, 92.8%, and 88.3% versus 86.4%, 87.5%, 90.2%, and 82.9%) and substantially reduced the rate of doubtful cases from 20% to 8% (P<0.001). DC+PET/CTA reclassified an additional 20% of cases classified as possible IE with DC+PET/nonenhanced CT. In addition, PET/CTA enabled detection of a significantly larger number of anatomic lesions associated with active endocarditis than PET/nonenhanced CT (P=0.006) or echocardiography (P<0.001). CONCLUSIONS: (18)F-FDG PET/CT improves the diagnostic accuracy of the modified DC in patients with suspected IE and prosthetic valves or cardiac devices. PET/CTA yielded the highest diagnostic performance and provided additional diagnostic benefits. PMID- 26276891 TI - Transcriptional Profiling of Breast Cancer Metastases Identifies Liver Metastasis Selective Genes Associated with Adverse Outcome in Luminal A Primary Breast Cancer. AB - PURPOSE: The complete molecular basis of the organ-specificity of metastasis is elusive. This study aimed to provide an independent characterization of the transcriptional landscape of breast cancer metastases with the specific objective to identify liver metastasis-selective genes of prognostic importance following primary tumor diagnosis. EXPERIMENTAL DESIGN: A cohort of 304 women with advanced breast cancer was studied. Associations between the site of recurrence and clinicopathologic features were investigated. Fine-needle aspirates of metastases (n = 91) were subjected to whole-genome transcriptional profiling. Liver metastasis-selective genes were identified by significance analysis of microarray (SAM) analyses and independently validated in external datasets. Finally, the prognostic relevance of the liver metastasis-selective genes in primary breast cancer was tested. RESULTS: Liver relapse was associated with estrogen receptor (ER) expression (P = 0.002), luminal B subtype (P = 0.01), and was prognostic for an inferior postrelapse survival (P = 0.01). The major variation in the transcriptional landscape of metastases was also associated with ER expression and molecular subtype. However, liver metastases displayed unique transcriptional fingerprints, characterized by downregulation of extracellular matrix (i.e., stromal) genes. Importantly, we identified a 17-gene liver metastasis-selective signature, which was significantly and independently prognostic for shorter relapse-free (P < 0.001) and overall (P = 0.001) survival in ER-positive tumors. Remarkably, this signature remained independently prognostic for shorter relapse free survival (P = 0.001) among luminal A tumors. CONCLUSIONS: Extracellular matrix (stromal) genes can be used to partition breast cancer by site of relapse and may be used to further refine prognostication in ER positive primary breast cancer. PMID- 26276892 TI - Preclinical Assessment of Efficacy of Radiation Dose Painting Based on Intratumoral FDG-PET Uptake. AB - PURPOSE: We tested therapeutic efficacy of two dose painting strategies of applying higher radiation dose to tumor subvolumes with high FDG uptake (biologic target volume, BTV): dose escalation and dose redistribution. We also investigated whether tumor response was determined by the highest dose in BTV or the lowest dose in gross tumor volume (GTV). EXPERIMENTAL DESIGN: FDG uptake was evaluated in rat rhabdomyosarcomas prior to irradiation. BTV was defined as 30% of GTV with the highest (BTVhot) or lowest (BTVcold) uptake. To test efficacy of dose escalation, tumor response (time to reach two times starting tumor volume, TGTV2) to Hot Boost irradiation (40% higher dose to BTVhot) was compared with Cold Boost (40% higher dose to BTVcold), while mean dose to GTV remained 12 Gy. To test efficacy of dose redistribution, TGTV2 after Hot Boost was compared with uniform irradiation with the same mean dose (8 or 12 Gy). RESULTS: TGTV2 after 12 Gy delivered heterogeneously (Hot and Cold Boost) or uniformly were not significantly different: 20.2, 19.5, and 20.6 days, respectively. Dose redistribution (Hot Boost) with 8 Gy resulted in faster tumor regrowth as compared with uniform irradiation (13.3 vs. 17.1 days; P = 0.026). Further increase in dose gradient to 60% led to a more pronounced decrease in TGTV2 (10.9 days; P < 0.0001). CONCLUSIONS: Dose escalation effect was independent of FDG uptake in target tumor volume, while dose redistribution was detrimental in this tumor model for dose levels applied here. Our data are consistent with the hypothesis that tumor response depends on the minimum intratumoral dose. PMID- 26276893 TI - Decrease in penicillin Sales in Brazil after over-the-counter restrictions. PMID- 26276894 TI - Reply to "decrease in penicillin sales in Brazil after over-the-counter restrictions". PMID- 26276895 TI - No robust evidence of lumefantrine resistance. PMID- 26276896 TI - Reply to "no robust evidence of lumefantrine resistance". PMID- 26276897 TI - Erratum for Mandelbrot et al., placental transfer of rilpivirine in an ex vivo human cotyledon perfusion model. PMID- 26276898 TI - Erratum for Grossman et al., target- and resistance-based mechanistic studies with TP-434, a novel fluorocycline antibiotic. PMID- 26276899 TI - Erratum for Johnson et al., intensity and mechanisms of fluoroquinolone resistance within the H30 and H30Rx subclones of Escherichia coli sequence type 131 compared with other fluoroquinolone-resistant E. coli. PMID- 26276901 TI - Weak-acid sites catalyze the hydrolysis of crystalline cellulose to glucose in water: importance of post-synthetic functionalization of the carbon surface. AB - The direct hydrolysis of crystalline cellulose to glucose in water without prior pretreatment enables the transformation of biomass into fuels and chemicals. To understand which features of a solid catalyst are most important for this transformation, the nanoporous carbon material MSC-30 was post-synthetically functionalized by oxidation. The most active catalyst depolymerized crystalline cellulose without prior pretreatment in water, providing glucose in an unprecedented 70 % yield. In comparison, virtually no reaction was observed with MSC-30, even when the reaction was conducted in aqueous solution at pH 2. As no direct correlations between the activity of this solid-solid reaction and internal-site characteristics, such as the beta-glu adsorption capacity and the rate of catalytic hydrolysis of adsorbed beta-glu strands, were observed, contacts of the external surface with the cellulose crystal are thought to be key for the overall efficiency. PMID- 26276902 TI - Bayesian inference in two-arm trials using relative belief ratios. AB - Various methodologies proposed for some inference problems associated with two arm trails are known to suffer from difficulties, as documented in Senn (2001). We propose an alternative Bayesian approach to these problems that deals with these difficulties through providing an explicit measure of statistical evidence and the strength of this evidence. Bayesian methods are often criticized for their intrinsic subjectivity. We show how these concerns can be dealt with through assessing the bias induced by a prior model checking and checking for prior-data conflict. PMID- 26276904 TI - Single-Flask Multicomponent Palladium-Catalyzed alpha,gamma-Coupling of Ketone Enolates: Facile Preparation of Complex Carbon Scaffolds. AB - A three-component palladium-catalyzed reaction sequence has been developed in which gamma-substituted alpha,beta-unsaturated products are obtained in a single flask by an alpha-alkenylation with either a subsequent gamma-alkenylation or gamma-arylation of a ketone enolate. Coupling of a variety of electronically and structurally different components was achieved in the presence of a Pd/Q-Phos catalyst (2 mol %), usually at 22 degrees C with yields of up to 85 %. Most importantly, access to these products is obtained in one simple operation in place of employing multiple reactions. PMID- 26276903 TI - State-dependent blocking mechanism of Kv 1.3 channels by the antimycobacterial drug clofazimine. AB - BACKGROUND AND PURPOSE: Kv 1.3 potassium channels are promising pharmaceutical targets for treating immune diseases as they modulate Ca(2+) signalling in T cells by regulating the membrane potential and with it the driving force for Ca(2+) influx. The antimycobacterial drug clofazimine has been demonstrated to attenuate antigen-induced Ca(2+) oscillations, suppress cytokine release and prevent skin graft rejection by inhibiting Kv 1.3 channels with high potency and selectivity. EXPERIMENTAL APPROACH: We used patch-clamp methodology to investigate clofazimine's mechanism of action in Kv 1.3 channels expressed in HEK293 cells. KEY RESULTS: Clofazimine blocked Kv 1.3 channels by involving two discrete mechanisms, both of which contribute to effective suppression of channels: (i) a use-dependent open-channel block during long depolarizations, resulting in accelerated K(+) current inactivation and (ii) a block of closed deactivated channels after channels were opened by brief depolarizations. Both modes of block were use-dependent and state-dependent in that they clearly required prior channel opening. The clofazimine-sensitive closed-deactivated state of the channel was distinct from the resting closed state because channels at hyperpolarized voltages were not inhibited by clofazimine. Neither were channels in the C-type inactivated state significantly affected. Kv 1.3 channels carrying the H399T mutation and lacking C-type inactivation were insensitive to clofazimine block of the closed-deactivated state, but retained their susceptibility to open-channel block. CONCLUSIONS AND IMPLICATIONS: Given the prominent role of Kv 1.3 in shaping Ca(2+) oscillations, the use-dependent and state-dependent block of Kv 1.3 channels by clofazimine offers therapeutic potential for selective immunosuppression in the context of autoimmune diseases in which Kv 1.3-expressing T cells play a significant role. PMID- 26276905 TI - A Unique Ternary Semiconductor-(Semiconductor/Metal) Nano-Architecture for Efficient Photocatalytic Hydrogen Evolution. AB - It has been a long-standing demand to design hetero-nanostructures for charge flow steering in semiconductor systems. Multi-component nanocrystals exhibit multifunctional properties or synergistic performance, and are thus attractive materials for energy conversion, medical therapy, and photoelectric catalysis applications. Herein we report the design and synthesis of binary and ternary multi-node sheath hetero-nanorods in a sequential chemical transformation procedure. As verified by first-principles simulations, the conversion from type I ZnS-CdS heterojunction into type-II ZnS-(CdS/metal) ensures well-steered collections of photo-generated electrons at the exposed ZnS nanorod stem and metal nanoparticles while holes at the CdS node sheaths, leading to substantially improved photocatalytic hydrogen-evolution performance. PMID- 26276906 TI - Ammonia-(Dinitramido)boranes: High-Energy-Density Materials. AB - Two ammonia-(dinitramido)boranes were synthesized by the reaction of dinitroamine with ammonia-borane. These compounds are the first reported examples of (dinitramido)boranes. Ammonia-mono(dinitramido)borane is a perfectly oxygen balanced high-energy-density material (HEDM) composed of an ammonia-BH2 fuel group and a strongly oxidizing dinitramido ligand. Although it is thermally not stable enough for practical applications, its predicted specific impulse as a solid rocket propellant would be 333 s. Its predicted performance as an explosive matches that of pentaerythtritol tetranitrate (PETN) and significantly exceeds that of trinitrotoluene (TNT). Its structure was established by X-ray crystallography and vibrational and multinuclear NMR spectroscopy. Additionally, the over-oxidized ammoniabis(dinitramido)borane was detected by NMR spectroscopy. PMID- 26276907 TI - Diagnosis And Management Of Deep Venous Thrombosis In The Emergency Department. AB - Although the clinical presentations of deep venous thrombosis are notoriously subtle and nonspecific, risk stratification tools such as the Wells clinical model have improved the efficiency of the diagnostic evaluation. The emergency clinician may be guided down several pathways, including D-dimer assays and/ or ultrasonography. New oral anticoagulants offer alternatives to the traditional heparins and vitamin K antagonists in the treatment of deep venous thrombosis. This review examines the current literature, evidence, and guidelines in the diagnosis and management of deep venous thrombosis. It also explores some of the controversies and developments regarding risk stratification, adjusted D-dimer thresholds,special populations, isolated distal deep venous thrombosis, upper extremity deep venous thrombosis, outpatient treatment, and the new oral anticoagulants. PMID- 26276908 TI - Evidence-Based Evaluation And Management Of Patients With Pharyngitis In The Emergency Department. AB - Pharyngitis is a common presentation, but it can also be associated with life threatening processes, including sepsis and airway compromise. Other conditions, such as thyroid disease and cardiac disease, may mimic pharyngitis. The emergency clinician must sort through the broad differential for this complaint using a systematic approach that protects against early closure of the diagnosis. This issue reviews the various international guidelines for pharyngitis and notes controversies in diagnostic and treatment strategies, specifically for management of suspected bacterial, viral, and fungal etiology. A management algorithm is presented, with recommendations based on a review of the best available evidence, taking into account patient comfort and outcomes, the need to reduce bacterial resistance, and costs. PMID- 26276910 TI - An Update on Diagnosis of Tracheomalacia in Children. AB - Congenital tracheomalacia is the most common congenital tracheal abnormality and occurs in approximately 1:2,100 children. Tracheomalacia can be isolated or associated with other airway anomalies such as laryngomalacia, bronchomalacia, and large laryngeal clefts. Also, an abnormal division of the embryonic foregut is frequently associated with congenital tracheomalacia; mostly in the form of proximal esophageal atresia with distal tracheoesophageal fistula. In such cases, the ratio between the cartilage ring and the posterior membranous wall drops from the normal ratio of 4 to 5:1 to 2 to 3:1. The diagnosis can be made upon clinical history and physical examination as well as by pulmonary function testing, computed tomography, dynamic magnetic resonance imaging, and fiberoptic bronchoscopy. Other approaches such as tracheobronchography have been used, but have not been validated for the diagnosis of tracheomalacia; fluoroscopy can be specific for diagnosing tracheomalacia, but lacks a reasonable sensitivity. Tracheomalacia is often self-limited and will resolve or become asymptomatic by the second year of life without intervention. For patients who remain symptomatic, possible treatments include pharmacotherapy, positive pressure application, and surgery. PMID- 26276911 TI - Editorial. AB - Dear Readers, In no time, we are almost halfway through 2015. Currently many issues concern psychiatrists, and does not fill them with optimism: an uncertain future implementation of the National Mental Health Protection Programme, or the recent amendment of criminal law, entering into force on 01.07.2015, on the significant enlargement of implementation of treatment and precautionary measures in psychiatric institutions. Prof. J.K. Gierowski [1] wrote in Psychiatria Polska about the misunderstanding and even conflict in this matter, between politicians, lawyers and psychiatric community, almost one and a half year ago. Several tragic, dramatic events (German Wings plane crash, the recent murder in Tworki) creates a bad social attitude towards the mentally ill. Our environment does not remain indifferent and is actively involved in the discussion - it is expressed by Letters to Editor, written by Elwira Marszalkowska-Krzes and Andrzej Brodziak, published in the current issue of the magazine. We are all aware of our responsibility - on the one hand for a safe environment for patients while ensuring adequate treatment to the ill, and on the other for creating the image of psychiatry and psychiatrists [2, 3]. (...). PMID- 26276912 TI - Sleep deprivation as a method of chronotherapy in the treatment of depression. AB - Disturbances of circadian rhythms play an important role in the pathogenesis of affective illnesses, and their normalisation with methods of chronotherapy might become an important element of therapeutic treatment. Chronotherapy is based on a controlled exposure to environmental stimuli which affect biorhythms. One of the chronotherapeutic methods is sleep deprivation (SD). The article discusses the present status of SD in psychiatry, its methods and application in depression treatment. Presently the most recommended pattern is combining total sleep deprivation (TSD), sleep phase advance (SPA), pharmacotherapy, and sometimes also phototherapy. Such proceedings have proven short-term and long-term effectiveness, and they may also have beneficial effect in drug resistant depression. Among the therapeutic mechanisms of the sleep deprivation treatment, the following are influenced: catecholaminergic, serotonergic and glutamatergic neurotransmission, neurotrophic factors (mainly the brain-derived neurotrophic factor - BDNF), the immune system, the endocrine system, metabolism of some brain structures (mostly the prefrontal cortex) and gene expression related to biological clock. On the grounds of the efficiency, simplicity and safety of this method, authors think that SD in its modern version with SPA should be used more often as an element of depression treatment. PMID- 26276913 TI - Natural products of relevance in the prevention and supportive treatment of depression. AB - The use of herbs or their parts: leaves, roots, rhizomes, flowers, seeds, natural strains, as well as extracts or isolated metabolites is becoming more and more popular. Natural remedies not only act prophylactically, but also help to alleviate symptoms of many diseases and enhance the overall functioning of the internal organs. Many raw materials of natural origin plays a role in treatment of health problems, and also in case of serious diseases such as depression. Depression (affective disorder) now affects about 10% of the population, but in next few years due to the development of civilization and increasing pace of life, the probable number of people suffering from this disease can grow rapidly. Natural raw materials such as Bacopa monnieri, Crocus sativus, Eleutherococcus senticosus, Griffonia simplicifolia, Hypericum perforatum, Sceletium tortuosum, Piper methysticum, Rhodiola rosea, Aspalathus linearis, Camellia sinensis, Ficus carica, Lycium chinense, Cuminum cyminum, Panax Ginseng can effectively assist the prevention and treatment of depression. Daily diet may also have positive effect in prevention of this disease. It was found that 5-hydroxy-L-tryptophan, L tryptophan (which are precursors of serotonin in the CNS), omega-3 fatty acids and anthranilic acid (vitamin L1) are able to improve mood. L-Tryptophan, 5 hydroxy-L-tryptophan are present in the largest quantities in the fruiting bodies of edible mushrooms. Omega-3 fatty acids are found in the flesh of fish, walnuts, soybeans, beans and chicken egg protein, while the anthranilic acid is commonly found in plants. PMID- 26276914 TI - Increased plasma pro-inflammatory cytokine concentrations after myocardial infarction and the presence of depression during next 6-months. AB - OBJECTIVES: The aim of this study was to investigate plasma concentrations of four pro-inflammatory cytokines (IL17a, IL6, TNFalpha and IL12p70) in patients with myocardial infarction and to analyse them according to presence of depression observed during first 6 months after myocardial infarction. METHODS: In 44 patients with the first acute STEMI (ST segment elevation myocardial infarction) plasma levels of IL17a, IL6, TNFalpha and IL12p70 were measured on the 3rd and 5th day after the MI. Cytokine concentrations were analyzed according to the presence of depression during 6 months of observation. RESULTS: Two groups of patients distinguished according to presence of depression during 6 months of observation differed in their inflammatory reaction to MI. In the depression group all four cytokines on the 3rd day after the MI were elevated compared to control and on the 5th day two of them: IL17a and IL6 were still elevated. In the group without depression on the 3rd day only two of four investigated cytokines were elevated and on the 5th day only IL6 concentration remained higher. CONCLUSIONS: It can be assumed that more pronounced inflammatory response as an element of stress reaction after MI can predispose to depression. IL17a increase can play particularly important role in this process. PMID- 26276909 TI - Metabotropic glutamate receptor subtype 5: molecular pharmacology, allosteric modulation and stimulus bias. AB - The metabotropic glutamate receptor subtype 5 (mGlu5 ) is a family C GPCR that has been implicated in various neuronal processes and, consequently, in several CNS disorders. Over the past few decades, GPCR-based drug discovery, including that for mGlu5 receptors, has turned considerable attention to targeting allosteric binding sites. Modulation of endogenous agonists by allosteric ligands offers the advantages of spatial and temporal fine-tuning of receptor activity, increased selectivity and reduced adverse effects with the potential to elicit improved clinical outcomes. Further, with greater appreciation of the multifaceted nature of the transduction of mGlu5 receptor signalling, it is increasingly apparent that drug discovery must take into consideration unique receptor conformations and the potential for stimulus-bias. This novel paradigm proposes that different ligands may differentially modulate distinct signalling pathways arising from the same receptor. We review our current understanding of the complexities of mGlu5 receptor signalling and regulation, and how these relate to allosteric ligands. Ultimately, a deeper appreciation of these relationships will provide the foundation for targeted drug design of compounds with increased selectivity, not only for the desired receptor but also for the desired signalling outcome from the receptor. Linked Articles This article is part of a themed section on Molecular Pharmacology of G Protein-Coupled Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.20/issuetoc. PMID- 26276915 TI - Symptoms of depression and anxiety after cardiac arrest. AB - OBJECTIVES: The aim of the study was to assess the incidence of depression and anxiety symptoms in patients after cardiac arrest (SCA) in relation to patients with a history of myocardial infarction without SCA and in healthy individuals. The analysis of the impact of selected socio-demographic and clinical parameters and duration of SCA on the presence and severity of depression and anxiety symptoms in different groups was also performed. METHODS: The study involved 30 patients after SCA and 31 patients with a history of myocardial infarction without SCA. The control group consisted of 30 healthy subjects. To assess the mental state, a specially developed questionnaire was used, while the presence and severity of the symptoms were assessed using the Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HAM-A). RESULTS: Statistically, a significantly higher average level of depression and a higher incidence of anxiety was demonstrated in patients after a sudden cardiac arrest (study group) and after myocardial infarction (reference group) compared with the control group. There were no statistically significant differences in the incidence of anxiety between the study and reference groups. No impact of the duration of cardiac arrest on the incidence of depression and anxiety symptoms in the study group was observed. CONCLUSIONS: In the group of people with a history of cardiac arrest, the most common mental disorder is depression. Anxiety and depression are significantly more frequent in patients with a history of SCA than in healthy individuals. There were no differences in the incidence and severity of depression symptoms in patients after SCA compared to patients after myocardial infarction without SCA. The described socio-demographic parameters and clinical characteristics had no impact on the symptoms of depression and anxiety in the investigated groups. PMID- 26276916 TI - Risk factors for suicide among children and youths with bipolar spectrum and early bipolar disorder. AB - In recent years much attention has been given to determine risk factors for suicide among adults with bipolar disorder. Such studies concerning children and youths, which would also take into account the specificity of the developmental age, are still too few. The ability to identify risk factors for children and youths with mood disorders, as well as the possibility to monitor them, is an essential element in preventing suicidal behaviours. Previous studies have clearly indicated that in the group of patients with an early onset of the bipolar disorder the occurrence of suicidal thoughts and intentions were significantly increased. Identifying the risk of suicide is hindered further by the complexity of the phenomenon, which is a compound interaction of various factors: biological, environmental, sociological, psychological and clinical. This is especially true with young adults suffering from mental illness and presenting a number of other psychopathological symptoms. The following paper introduces and reviews the results of current studies, which analysed the risk factors for suicide among children and youths with bipolar spectrum or already diagnosed with bipolar disorder. For this purpose we conducted the overview of recent years literature available in PubMed/MEDLINE database, including the following search criteria: early onset bipolar disorder, bipolar disorder in children and young people, the spectrum of bipolar disorder, and suicidal ideation, suicidal intent, suicide. PMID- 26276917 TI - Effectiveness of therapy in terms of reduction of intensity and elimination of suicidal ideation in day hospital for the treatment of neurotic and behavioral disorders. AB - OBJECTIVES: Analysis of changes in prevalence and intensity of suicidal ideation (SI) in patients who underwent an intensive psychotherapy conducted in integrative approach with predominance of psychodynamic approach in the Day Hospital for Neurotic and Behavioral Disorders. METHODS: Symptom checklist KO"O" and Life Inventory completed by 461 women and 219 men who were treated in the day hospital due to neurotic, behavioral and personality disorders in 2005-2013. RESULTS: Patients initially reporting SI showed greater than others global intensity of the neurotic symptoms (p < 0.001 for both sexes) and greater intensity in almost all the neurotic symptoms scales. Improvement (elimination or reduction of intensity) in terms of SI was observed in 84.3% of women and 77.5% of men. The prevalence of SI-reporting patients decreased substantially from 29.1% to 10.2% in women and from 36.5% to 13.7% in men. CONCLUSIONS: The patients reporting SI before the commencement of psychotherapy constituted a large part of the studied population - approximately 1/3. They showed greater intensity of neurotic symptoms than those who were not reporting SI. Intensive psychotherapy in the day hospital was characterized by high effectiveness in terms of reduction and elimination of SI. Prevalence of SI in both women and men until the end of therapy decreased almost three times. Cases of improvement in terms of SI were several times more frequent than cases of deterioration in terms of SI (increase in its intensity or its occurrence at the end of therapy). Etiopathogenesis of SI and its methods of treatment require further research. PMID- 26276918 TI - Self-mutilating behaviours in patients with mental disorders - a study on users of a social networking service. AB - OBJECTIVES: This work is aimed at gaining extended knowledge of self-destructive behaviours. Users of a social networking service devoted to people with mental disorders took part in the study. METHODS: The study was carried out as a voluntary web questionnaire based on clinical experience of researchers and literature. Results were summed up using standard method of descriptive statistics. RESULTS: 202 users of the web portal psychiatrically identified with various mental disorders participated in the study (information derived from responses given in the questionnaire). Patients afflicted by bipolar disorder and recurrent depressive disorders (72.7%) constituted the biggest group. Those previously thinking of self-harm have done it nine times more frequently, the majority under 20 years of age. These behaviours included self-mutilations (56.4%) and deliberate self-poisoning (53.5%). The biggest group of patients who declared self-harm in the past were afflicted by mood disorders (BD - 77.3%, RDD 71.2%); however, the difference is not statistically significant. Such behaviours were reported 2.5 times more frequently (p < 0.05) by patients with identified co-occurrence of personality disorders. Thoughts of self-harm appeared not only in full-blown episodes. Regardless of the identified mental disorder, self-harming behaviours were accompanied by despondency and resignation. Approximately 10% of respondents talked about their self-harming behaviours with a psychiatrist and a psychotherapist, i.e. 1.5 times more frequently than with other people from their surroundings. Suicide attempts and completed suicides occurred much more frequently within surveyed families than in the general population. CONCLUSIONS: Self-mutilations occur mostly in patients suffering from various affective disorders. In spite of obvious restrictions of this study method, a web portal may be an effective way to collect data, for it provides fully anonymous responses. PMID- 26276919 TI - Dyadic death - depression and borderline personality. AB - OBJECTIVES: This work aims to present the difficulties in the assessment of sanity of a perpetrator involved in the so-called dyadic death, which in Poland is identified with the occurrence of sever mood disturbances at the time of the crime. METHODS: CASE: A case of a man who killed his wife and two children is presented. The perpetrator himself tried to commit suicide by cutting his veins with a razor. CONCLUSIONS: COMMENTARY: The authors underline diagnostic difficulties which were encountered in the analysed case, they point out the necessity to go beyond the phenomenological aspect of "dyadic death" and the need for multidimensional clinical evaluation of the perpetrator. The rarity of similar acts and low survival rate of perpetrators leaves experts with relatively small amount of opinion giving experience. Thus, there is a need for high accuracy research and careful consideration. PMID- 26276920 TI - Differentiation of indirect self-destructiveness due to sex (gender) in individuals after suicide attempts. AB - OBJECTIVES: The aim of this study was to examine the sex (gender) differentiation of indirect self-destructiveness as a generalised behavioural tendency and its manifestations in individuals who attempted suicides. METHODS: 147 individuals (114 females and 33 males) after suicide attempts were studied; the reference group consisted of 558 individuals (399 females and 159 males). Indirect self destructiveness was examined by means of the Polish version of the Chronic Self Destructiveness Scale (CS-DS) including Transgression and Risk (A1), Poor Health Maintenance (A2), Personal and Social Neglects (A3), Lack of Planfulness (A4) and Helplessness, Passiveness in the Face of Problems/Difficulties (A5). RESULTS: Sex (gender) and suicide attempt significantly differentiate scores of the subjects on all indices/scales of indirect self-destructiveness. Scores of individuals after suicide attempts are considerably higher on almost all scales. In that group, significant differences between females and males occurred on the A2-Poor Health Maintenance, A3-Personal and Social Neglects, A4-Lack of Planfulness and A5-Helplessness scales. It was only on the A2-Poor Health Maintenance scale that females achieved higher scores. CONCLUSIONS: The intensity of indirect self destructiveness in females who attempted suicides achieved the level observed in males who attempted suicides. Poor health maintenance was also more intense in them than in the group of males. Males after suicide attempts displayed the lowest poor health maintenance. Results of this study may have preventive and therapeutic implications. PMID- 26276921 TI - Indirect self-destructiveness in homosexual individuals. AB - OBJECTIVES: The aim of this study was to comprehensively examine the syndrome of indirect self-destructiveness in homosexual individuals. METHODS: 156 homosexual individuals (111 males, 45 females) aged 25-35 (mean age of 29.6) and 561 heterosexual individuals (400 males, 161 females) aged 24-36 (mean age of 28.2) were studied with regard to indirect self-destructiveness. The research instrument was the Polish version of the Chronic Self-Destructiveness Scale (CS DS) including: Transgression and Risk (A1), Poor Health Maintenance (A2), Personal and Social Neglects (A3), Lack of Planfulness (A4) and Helplessness and Passiveness in the face of problems (A5). RESULTS: Homosexual individuals obtained significantly higher scores than heterosexual ones in numerous scales: Indirect Self-Destructiveness - global (general) index (p<0.001), A1 Transgression and Risk (p<0.001), A4-Lack of Planfulness (p<0.001) and A5 Helplessness, Passiveness (p=0.04) There were no significant differences in the Poor Health Maintenance scale (A2). They also achieved significantly higher scores in the subscales assessing using of psychoactive substances. Factor analysis revealed the presence of only one factor both in the group of homosexual and heterosexual individuals. CONCLUSIONS: The research results indicate that, as compared with the group of heterosexual individuals, in the group of homosexuals there occurs a worsening in psychological functioning, which may be also manifested by an increased indirect self-destructiveness index. The increased intensity of indirect self-destructiveness in homosexual individuals may be considered a manifestation of worsened psychological functioning. The homosexual individuals look after their health similarly to heterosexuals. PMID- 26276922 TI - Satisfaction with life, self-esteem and evaluation of mental health in people with tattoos or piercings. AB - OBJECTIVES: The aim of the study was to determine the level of life satisfaction and the various dimensions of self-esteem of pierced or tattooed people, and evaluate their mental health, compared to those without similar body modifications. METHODS: The study was conducted on a sample of 449 people aged 16 58 years (mean age 26.7 +/- 6.35), of whom 308 had body modifications: tattoo (n = 90), body piercings in places other than the ear lobe (n = 53), or both tattoos and piercings (n = 165). The control group consisted of 141 people without such modifications. The participants completed a questionnaire concerning their socio demographic status, as well as the following psychological tests: The Satisfaction with Life Scale (SWLS), Multidimensional Self-Esteem Inventory (MSEI) and General Health Questionnaire (GHQ-28). RESULTS: Our findings show no significant differences in terms of life satisfaction between the group with tattoos or piercings and the control group. People with body modifications were characterized by higher self-esteem, with regard to their competence and leadership abilities. They also display fewer symptoms of social impairment and sleep disorders than the control group. CONCLUSIONS: Tattoos and piercings should not be considered as indicators of psychopathology. PMID- 26276923 TI - Examining mentalizing ability in the process of psychiatric and psychotherapeutic diagnosis. AB - The present paper discusses the problem of examining ability to mentalize in the psychiatric and psychotherapeutic diagnosis process. It is proved by the research results indicating significance of mentalization in the psychosocial functioning of an individual, the relation between the level of this ability and the appearance of the specific mental disorders and problems, and its role in the treatment process. The paper describes and analyses the classic tool for studying mentalization - Reflective Functioning Scale. The present paper points to the advantages of this tool - good reliability, high criterion and theoretical validity, enabling studying complexity of a phenomenon, and introduction of non specific therapeutic factors into the diagnostic process. The limitations of the tool are also mentioned - high cost borne by a researcher and an examined person, the complexity of the interview collection and analysis procedure and the inability of repeated application of the tool to evaluate treatment effects. The paper also presents an alternative method of studying mentalization that uses questionnaire tools. The text describes the advantages of the questionnaire in assessing a reflective function: first and foremost, its low cost and an easy repeatability of the test. The paper also shows the limitations of this tool in describing the subject phenomenon: inability to describe the complexity of the phenomenon, simplified results and low theoretical validity. PMID- 26276924 TI - Psychotherapy of nonheterosexual people from the perspectives of therapists and patients - bilateral expectations and concerns. AB - OBJECTIVES: The aim of the study was to show the differences in declared therapeutic goals and priorities, and in concerns about the therapeutic process, between LGB (lesbians, gays and bisexual people) people and psychotherapists. METHODS: Participants from both groups fulfilled semi-structured questionnaire, which was anonymously available on-line through the link sent together with the invitation to participate in the study. LGB people were contacted through the biggest Internet site for non-heterosexual people in Poland. The invitation was also sent to the psychotherapists, members of the Polish Psychiatric Association. The questions and responses in both versions of the questionnaire were formulated in that way, so as to enable adequate comparisons. RESULTS: The two most important therapeutic goals for respondents in both groups were: help in the acceptance of sexual orientation and emotional support with the difficulties of living in a hostile environment. The most common concerns for LGB people were that psychotherapists might attempt to change their sexual orientation, whereas for psychotherapists, the most common concern was that they would be helpless in the face of the social situation of LGB people. CONCLUSIONS: Psychotherapists and LGB people basically agreed upon the therapeutic aims of psychotherapy. The adverse social situation of non-heterosexual people in Poland is a source of their concerns about the psychotherapeutic relations. On the other side the concerns of psychotherapists seem to correspond to some degree with the concerns of LGB people. They both reflect the society, which still struggles with heterosexism and homophobia. PMID- 26276925 TI - The sense of identity and symptoms of personality disorders - The results of a non-clinical population study. AB - OBJECTIVES: The aim of the presented studies was to empirically analyze the relation between the symptoms of personality disorders and the structure of identity-related senses. The analyses were conducted within two models - based on Millon's theory of personality and DSM-IV personality disorder classification system. METHODS: In the studies, a total of 197 university students of various majors were included. The authors used Polish version of the Millon Index of Personality Styles that assess personality styles and offers a Clinical Index to evaluate psychological adjustment, and Personality Disorder Types Questionnaire to obtain DSM-IV diagnoses. The intensity of the identity-related senses was measured using the Multidimensional Identity Inventory. Data were tested for normality, and then Student's t-tests and ANOVA tests were used to compare the structure of identity-related senses in individuals with a healthy personality and disordered personality. RESULTS: Within Millon's model, three different patterns of disordered personality were found, and they all manifested some identity deficits. Most of the personality disorders covered by DSM-IV also significantly differed on the identity dimensions from healthy personality. CONCLUSIONS: The results show that identity deficits should be considered as an important symptom of personality disorders, regardless of the adopted model of personality. The most disordered identity is observed in individuals falling into the group with odd or eccentric disorders and into the anxious or fearful cluster. The group with dramatic, emotional or erratic disorders is the most heterogeneous in terms of the level of identity disorganization. PMID- 26276926 TI - Disturbances of sleep continuity in women during the menopausal transition. AB - OBJECTIVES: The objective of the study was to evaluate the prevalence of sleep continuity disorders in women during menopausal transition, to evaluate the relationship between disturbances of sleep continuity and the severity of menopausal syndrome and the occurrence of various symptoms of this syndrome, as well as to evaluate the association between the presence of sleep disturbances and serum concentrations of gonadotropins, prolactin and sex hormones. METHODS: Consecutive 140 women (mean age 54.4 +/- 4.7 years) searching for the treatment in the Clinic for Gynaecological Endocrinology who reported symptoms of menopausal syndrome were investigated. The type and severity of disturbances of sleep continuity were evaluated using a survey based on the sleep related questions from Hamilton Depression Rating Scale. The severity of symptoms of menopausal syndrome was assessed using the Kupperman Index. The concentration of the following hormones in blood serum was tested: FSH, LH, 17beta-estradiol, PRL, total testosterone, DHEAS and SHBG. RESULTS: Disturbances of sleep continuity were a prevalent complaint in the studied group of women. Difficulties in falling asleep were found in 57.8% of women, difficulties in maintaining sleep in 70%, waking up too early in 60.7%. The severity of all three types of sleep continuity disturbances was related to the severity of menopausal syndrome as measured with Kupperman Index (Spearman correlation coefficient r = 0.63, r = 0.61, r = 0.52, respectively; p < 0.001). Difficulties in maintaining sleep were negatively correlated with the concentration of FSH (r = - 0.19; p < 0.05), 17beta-estradiol (r = - 0.19; p < 0.05) and SHBG (r = - 0.18; p < 0.05), difficulties in falling asleep negatively correlated with the concentration of 17beta-estradiol in the blood serum (r = - 0.19; p < 0.05). CONCLUSIONS: Sleep continuity disturbances are frequently reported by women during the menopausal transition. Interventions aimed at reducing the symptoms of menopausal syndrome should be considered as important action to improve sleep quality in this population of patients. PMID- 26276927 TI - The early childhood sexual experiences and collusion in adult partner relationship. AB - OBJECTIVES: The aim of the present research was verification of the hypothesis for the influence of negative sexual experiences in sexual development on the quality of partner relationships in the adult life. Special attention was given to the influence exercised by the level of erotization in the environment of the family of origin and to the experience of child sexual abuse. The quality of partner relationships was recognized using Jurg Willi's concept through the analysis of intensity of dysfunctions (collusions) in those relationships. METHODS: The study was conducted on a population of 170 adults in partnerships. The surveyed group filled in the Questionnaire on Models of Sexual Upbringing in Families, the Couples Collusion Questionnaire and the Questionnaire on Sexual Abuse of Children. RESULTS: Positive interrelation has been confirmed between the level of erotization in the family of origin and the oral, anal and oedipal partner collusion in the procreative relationships of individuals. Such link has not been confirmed for narcissistic collusion. The interrelation between the sexually abusive experiences and the partner collusion has only been confirmed in masculine group within the oral collusion and the anal collusion. CONCLUSIONS: The findings largely support the assumption that there is a connection between the character of sexual experiences in childhood and functioning in adult partnership. PMID- 26276928 TI - Letter to Editor. Prerequisites for psychiatric examination detecting the intention to commit suicide. AB - The recent plane crash caused by the pilot increased the interest in the possibility of medical examination, which would be able to detect the intention of committing suicide. The development of such a diagnostic procedure is not only important for the prevention of events in the civil and military aviation, but also due to increase in the incidence of various suicide terrorist acts. The author expresses his opinion on the nature of such examination, due to his experience of working in Acute Poisoning Treatment Centre. The Centre admits about 1 000 patients per year, who have been rescued after suicide attempts made by the intake of a toxic substance. He discusses the developed scheme of structuralized interview, however, he believes that the ability to detect the existence of suicidal ideation was significantly improved as a result of the formulation of Interpersonal Theory of Suicide, which distinguishes four stages: 1) passive suicidal ideation, 2) suicidal desire, 3) suicidal intent, 4) lethal and near lethal suicide attempts. Next, the author presents his own prediction of the development of methods, enabling the objective detection of "suicidal intent" (plan). In his opinion, such an examination in the future, would be based on brain imaging techniques, which could detect the specific configuration of a person's brain neural circuits representing the existing plan of suicide. The real ability to detect such a configuration of neural circuits can be predicted on the basis of new, quoted results of neurophysiological studies. PMID- 26276929 TI - Letter to the Editors. Professional confidentiality applicable to psychiatrists. AB - Psychiatrists performing activities under the Mental Health Protection Act who in connection with their performance of such activities become aware of information that, if kept confidential, can constitute a threat to the life or health of the patient or other people, are released from the duty to keep such information confidential. In such a case, they have a moral and legal duty to disclose such information to law enforcement authorities and cannot be prosecuted under criminal law for disclosing such confidential information. An attempt to interrogate a physician who files such a report regarding circumstances of which he became aware while performing activities under the Mental Health Protection Act will, however, be illegal. Yet, that leads to disputes and controversies in the medical and legal communities, and, therefore, the issue requires a prompt, uniform interpretation. Due to the expected increase in attempted dyadic deaths (after the Germanwings plane crash,) the problem should be carefully regulated so that psychiatrists know the legal boundaries of dealing with patients - potential suicides. PMID- 26276930 TI - Letter to Editor. New assessment of the validity of the Brief Measure to Assess Perception of Self-Influence on the Disease Course: A Version for Schizophrenia. AB - INTRODUCTION: Clinical observations suggest that the Brief Measure to Assess Perception of Self-Influence on the Disease Course: A Version for Schizophrenia has the better reliability, than presented in the original publication of the scale [1]. It is used in research and their results indicate moderate relations between the perception of the self-influence on schizophrenia course and social functioning as well as adherence to the recommended treatment. These circumstances justify and new assessment of the reliability of the scale. MATERIAL AND METHODS: Detailed scale for competent judges, who had better opportunity for the comprehensive examination of 59 participants, 27 men and 29 women of age 22-72 lat (M = 40.69; SD = 11.85). RESULTS: The Spearman's correlation between the scores on the version for schizophrenia of the Brief Measure to Assess Perception of Self-Influence on the Disease Course and the assessment of the patients' perception of self-influence on the schizophrenia course by the competent judges rho was 0.56. Whereas, in the first study Pearson's r was 0.45. CONCLUSIONS: Brief Measure to Assess Perception of Self Influence on the Disease Course - Version for Schizophrenia has good enough validity, as for so brief scale. It can be used in research and clinical practice. PMID- 26276931 TI - Agencies raise health concerns over treatment of Kos migrants. PMID- 26276933 TI - Postsurgical Inflammation as a Causative Mechanism of Venous Thromboembolism. AB - Surgery is associated with an increased risk of venous thromboembolic events (VTE) including deep vein thrombosis and pulmonary embolism. Although the current treatment regiments such as mechanical manipulation and administration of pharmacological prophylaxis significantly reduced the incidence of postsurgical VTE, they remain a major cause of postoperative morbidity and mortality worldwide. The pathophysiology of venous thrombosis traditionally emphasizes the series of factors that constitute Virchow triad of factors. However, inflammation can also be a part of this by giving rise to a hypercoagulable state and endothelial damage. The inflammatory response after surgery, which is initiated by a cytokine "storm" and occurs within hours of surgery, creates a prothrombotic environment that is further accentuated by several cellular processes including neutrophil extracellular traps formation, platelet activation, and the generation of tissue factor-bearing microparticles. Although such inflammatory markers are elevated in undergoing surgery, the precise mechanism by which they give rise to venous thrombosis is poorly understood. Here, we discuss the potential mechanisms linking inflammation to thrombosis, and highlight strategies that may minimize surgical inflammation and reduce the incidence of postoperative VTE. PMID- 26276932 TI - Role of Pex21p for Piggyback Import of Gpd1p and Pnc1p into Peroxisomes of Saccharomyces cerevisiae. AB - Proteins designated for peroxisomal protein import harbor one of two common peroxisomal targeting signals (PTS). In the yeast Saccharomyces cerevisiae, the oleate-induced PTS2-dependent import of the thiolase Fox3p into peroxisomes is conducted by the soluble import receptor Pex7p in cooperation with the auxiliary Pex18p, one of two supposedly redundant PTS2 co-receptors. Here, we report on a novel function for the co-receptor Pex21p, which cannot be fulfilled by Pex18p. The data establish Pex21p as a general co-receptor in PTS2-dependent protein import, whereas Pex18p is especially important for oleate-induced import of PTS2 proteins. The glycerol-producing PTS2 protein glycerol-3-phosphate dehydrogenase Gpd1p shows a tripartite localization in peroxisomes, in the cytosol, and in the nucleus under osmotic stress conditions. We show the following: (i) Pex21p is required for peroxisomal import of Gpd1p as well as a key enzyme of the NAD(+) salvage pathway, Pnc1p; (ii) Pnc1p, a nicotinamidase without functional PTS2, is co-imported into peroxisomes by piggyback transport via Gpd1p. Moreover, the specific transport of these two enzymes into peroxisomes suggests a novel regulatory role for peroxisomes under various stress conditions. PMID- 26276934 TI - Endothelial Dysfunction and Altered Coagulation As Mediators of Thromboembolism in Behcet Disease. AB - Behcet disease (BD) is a rare multisystem, inflammatory disease of unknown etiology with vascular involvement and associated thrombogenicity. This review aims to describe the involvement of various mediators in endothelial cell damage and in the hypercoagulable state of BD. The scenario of the chronic inflammation present in BD shows an increased oxidative condition that contributes to endothelial cell damage and induces platelet, leukocyte, and endothelial cell activation through the release of proinflammatory cytokines and chemokines. These factors, together with the increased levels of homocysteine observed in BD patients, induce the endothelial cell expression of adhesion molecules (VCAM-1 and ICAM-1) and tissue factor; the release of cytokines, soluble CD40L (sCD40L), matrix metalloproteinase-9, and blood coagulation factor V; the inhibition of fibrinolysis; the disruption of nitric oxide metabolism; and the increase in platelet reactivity and lipid peroxidation. Endothelial cell dysfunction leads to a prothrombotic and antifibrinolytic phenotype in BD patients. Increased levels of homocysteine, fibrinogen, and plasminogen activator inhibitor type 1 seem to be involved in the procoagulant condition of this pathology that has been verified by end-point tests as well as by global coagulation tests. PMID- 26276935 TI - Antiphospholipid Syndrome--Not a Noninflammatory Disease. AB - The autoimmune disease antiphospholipid syndrome (APS) is characterized by thrombosis or pregnancy morbidity in patients with persistent antiphospholipid antibodies (aPLs). Although inflammation is not a key feature of the clinical presentation of the syndrome, there are indications that the inflammatory response plays an important role in APS. The major antigen of aPLs, the plasma protein beta2-glycoprotein I, is involved in clearance of microparticles and in the innate immune response. In light of these physiological functions, the formation of antibodies against the protein is easily understood, as antibodies might augment the clearance reaction. In addition, inflammatory mediators are thought to play a role in the activation of leukocytes and the induction of endothelial dysfunction in APS. Moreover, evidence for a role of complement activation in the pathogenesis of the syndrome is accumulating. This review will provide an overview of current knowledge on the physiological function of beta2 glycoprotein I, the formation of autoantibodies against beta2-glycoprotein I and will explore the contribution of inflammation to the clinical manifestations of APS. PMID- 26276936 TI - Thrombosis, Microangiopathies, and Inflammation. AB - Thrombotic microangiopathy (TMA) is characterized by the presence of microangiopathic hemolytic anemia and thrombocytopenia. There are several disorders with varied etiopathogenesis, both genetic and acquired, that result in TMA. The neutrophils play an important role in inflammation and thrombosis through the formation of neutrophil extracellular traps (NETs). NETs are formed in response to a variety of stimuli including infections, chemical factors, and platelet activation. The classic TMA, thrombotic thrombocytopenic purpura (TTP) is caused by a severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type-I motif, member 13), mostly acquired due to autoantibodies, whereas atypical hemolytic uremic syndrome (aHUS) is mostly attributed to genetic defects in complement pathway regulatory proteins. The management of these well-known disorders has evolved over the last decade. Similarly, there is also better understanding of diverse and unusual clinical presentations of both of these conditions. Since there are many other causes of TMAs, which may mimic some of the clinical features of TTP or aHUS, it is essential to thoroughly investigate each patient so that appropriate therapy can be offered. This review focuses on some important developments in understanding of etiopathogenesis, diagnosis, and treatment of more commonly encountered TMAs. PMID- 26276937 TI - The Role of Blood-Borne Microparticles in Inflammation and Hemostasis. AB - Inflammation has a pivotal role in cardiovascular disease because it contributes to the progression of atherosclerosis, a chronic inflammatory disease of the vessel wall. Microparticles (MPs) have recently emerged as both surrogate markers for different cardiovascular conditions (i.e., biomarkers of vascular inflammation and coagulation) and paracrine biological shuttle modules with influence in target cells. MPs are vesicles that bud off from cells, lack a nucleus, contain a membrane skeleton, and are defined by their size and expression on their surface of antigens specific of parental cells. Interestingly, not only inflammation is one of the main stimuli causing MP release but also MPs, in its turn, can induce, regulate, and even in specific cases reduce inflammation. The present review aims to summarize and update the role of circulating MPs in inflammation and hemostasis with special emphasis on their novel associations and functions. Besides their role as biomarkers of atherosclerotic inflammation, blood-borne MPs possess mechanisms to alter vascular cell milieu, to disseminate proinflammatory mediators, and to spread the inflammatory cascade reaction, causing a chronic inflammation of the vascular wall and aggravating the atherothrombotic process. PMID- 26276938 TI - Platelets in Inflammatory Disorders: A Pathophysiological and Clinical Perspective. AB - Platelets are well recognized as a key cell component of the hemostatic system. Recently, several additional functions have been discovered for these blood cells but most importantly in the process of inflammation. Numerous research groups have demonstrated crucial roles for platelets in the pathogenesis of varied clinical conditions where inflammation is important. Alterations in both platelet number and function have been observed with these different conditions. The relevance of these findings is their therapeutic implications through simple antiplatelet therapy to more complex, as yet clinically untrialed options, like interfering with platelet-leukocyte or platelet-endothelial interaction. This review focuses on how platelets are relevant in inflammatory conditions with an impetus on the clinical aspects. PMID- 26276939 TI - Time for a Revolution in AMEDD Doctrine. PMID- 26276940 TI - Baseline Susceptibility to Pyrethroid and Organophosphate Insecticides in Two Old World Sand Fly Species (Diptera: Psychodidae). AB - Phlebotomine sand flies are blood-feeding insects that transmit Leishmania parasites that cause various forms of cutaneous and visceral leishmaniasis and sand fly fever viruses (Phlebovirus; Bunyaviridae) in humans. Sand flies pose a significant threat to US military personnel deployed to Leishmania-endemic and sand fly fever endemic regions which include Europe, the Mediterranean basin, Middle East, Central Asia, Southwest Asia, and Africa. A research project supported by the Department of Defense Deployed Warfighter Protection Program was initiated to evaluate the susceptibility of 2 Old World sand fly species, Phlebotomus papatasi and P duboscqi, to a number of commonly used pyrethroid and organophosphate insecticides. A new glass vial bioassay technique based on the CDC bottle assay was developed for this study. The exposure time-mortality relationship at a given insecticide concentration was determined for each insecticide, and their relative toxicity against the 2 sand fly species was ranked based on bioassay results. This study validated the new bioassay technique and also generated baseline insecticide susceptibility data to inform future insecticide resistance monitoring work. PMID- 26276941 TI - Efficacy of Permethrin Treated Bed Nets Against Leishmania major Infected Sand Flies. AB - Insecticide treated nets (ITNs) are a potential tool to help control sand flies and prevent Leishmaniasis. However, little is currently known about the response of Leishmania infected sand flies to ITNs. In this study, Phlebotomus duboscqi sand flies were infected with the parasite Leishmania major. Infected and noninfected sand flies were then evaluated against permethrin treated and untreated bed nets in a laboratory assay that required sand flies to pass through suspended netting material to feed on a mouse serving as an attractive host. The number of sand flies passing through the nets and blood feeding was recorded. There was not a significant difference in the ability of infected or noninfected sand flies to move through treated or untreated nets. Fewer sand flies entered the permethrin treated nets compared to the untreated nets, indicating that permethrin creates an effective barrier. The results show that in addition to reducing the nuisance bites of noninfected sand flies, ITNs also protect against Leishmania infected sand flies and therefore can play in key role in reducing the rates of Leishmaniasis. This study is important to the Department of Defense as it continues to develop and field new bed nets to protect service members. PMID- 26276942 TI - Controlled Human Malaria Infection at the Walter Reed Army Institute of Research: The Past, Present, and Future From an Entomological Perspective. AB - Thirty years ago, the Entomology Branch at the Walter Reed Army Institute of Research (WRAIR) performed the first controlled human malaria infection, in which lab-reared mosquitoes were infected with lab-cultured malaria parasites and allowed to feed on human volunteers. The development of this model was a turning point for pre-erythrocytic malaria vaccine research and, through decades of refinement, has supported 30 years of efficacy testing of a suite of antimalarial vaccines and drugs. In this article, we present a historical overview of the research that enabled the first challenge to occur and the modifications made to the challenge over time, a summary of the 104 challenges performed by WRAIR from the first into 2015, and a prospective look at what the next generation of challenges might entail. PMID- 26276943 TI - Mosquito Fauna of Lao People's Democratic Republic, with Special Emphasis on the Adult and Larval Surveillance at Nakai District, Khammuane Province. AB - This article includes the distribution records and updated checklist of mosquitoes (Culicidae, Diptera) from the Lao People's Democratic Republic (PDR), based on the literature, specimens deposited at the US National Museum of Natural History mosquito collections, and our recent field collections from the Nakai District, Khammuane Province. Ten of 101 species in the updated checklist of mosquitoes are new records for the Lao PDR. PMID- 26276944 TI - Records and Distribution of New World Phlebotomine Sand Flies (Psychodidae, Diptera), With Special Emphasis on Primary Types and Species Diversity. AB - This article includes the records and distribution of Phlebotomine sand flies (Psychodidae, Diptera) in the New World based on the specimen collections housed in 2 repositories, the US National Museum of Natural History and the Museum of Entomology, Florida State Collection of Arthropods. Approximately 128 species have primary types housed in the 2 repositories, including holotypes (47 species, 3 subspecies), "types" (7 species), allotypes (52 species, 6 subspecies), lectotypes (4 species), paratypes (93 species, 10 subspecies), and neoallotype (1 species), mounted on slides, with a total of 1,107 type slides. For species diversity, collection data from 24 countries in the sand fly database were analyzed according to the number of species present, specimen records, decade of collections, and countries where collections were conducted. PMID- 26276945 TI - Development of Air Force Aerial Spray Night Operations: High Altitude Swath Characterizations. AB - Multiple trials were conducted from 2006 to 2014 in an attempt to validate aerial spray efficacy at altitudes conducive to night spray operations using night vision goggles (NVGs). Higher altitude application of pesticide (more than 400 ft (121.9 m) above ground level (AGL)) suggested that effective vector control might be possible under ideal meteorological conditions. A series of lower altitude daytime applications (300 ft (91.4 m) AGL) demonstrated effective and repeatable mortality of target sentinel insects more than 5,000 ft (1,524 m) downwind, and control of natural vector populations. From these results we believe further pursuit of aerial night applications of pesticide using NVGs at 300 ft (91.4 m) AGL by this group is warranted. PMID- 26276946 TI - Toxicity Testing in the 21st Century: Refining the Army's Toolbox. PMID- 26276947 TI - The New US Military Role in the European Union's Import Program: Strategic Implications Ensuring Safe Food for the European Theater. PMID- 26276948 TI - Evaluation of Postdeployment Cancers Among Active Duty Military Personnel. PMID- 26276949 TI - A Preliminary Analysis of Noise Exposure and Medical Outcomes for Department of Defense Military Musicians. AB - Noise exposure is a known occupational health hazard to those serving in the military. Previous military epidemiology studies have identified military occupations at risk of noise induced hearing loss (NIHL); however, musicians have not been specifically mentioned. The focus of military NIHL studies is usually on those service members of the combat arms occupations. This project was a preliminary examination of Department of Defense (DoD) active duty military musicians in regard to their noise exposure, annual hearing test rates, and hearing injury rates using available data sources. The analysis concluded that DoD military musicians are an underserved population in terms of hearing conservation efforts. Noise surveillance data extracted from the Defense Occupational and Environmental Health Readiness System-Industrial Hygiene showed that every musician similar exposure group (SEG) with noise survey data from 2009 to 2013 exceeded the occupation exposure level adopted by DoD Instruction 6055.12. However, only a small percentage of all DoD active duty military musicians (5.5% in the peak year of 2012) were assigned to a SEG that was actually surveyed. Hearing test data based on Current Procedural Terminology coding extracted from the Military Health System revealed that the percentage of musicians with annual hearing tests increased over the 5 years studied in all services except the Air Force. During 2013, the data showed that the Navy had the highest percentage of musicians with annual hearing tests at 70.9%, and the Air Force had the lowest at 11.4%. The Air Force had the highest percentage of hearing injuries of those musicians with annual hearing tests for all 5 years analyzed. Although noise surveillance and annual hearing tests are being conducted, they occur at a much lower rate than required for a population that is known to be overexposed to noise. PMID- 26276950 TI - The Benefits of Deploying Health Physics Specialists to Joint Operation Areas. AB - Preventive Medicine Specialists (military occupational specialty [MOS] 68S) with the health physics specialist (N4) qualification identifier possess a unique force health protection skill set. In garrison, they ensure radiation exposures to patients, occupational workers and the public from hospital activities such as radioisotope therapy and x-ray machines do not to exceed Federal law limits and kept as low as reasonably achievable. Maintaining sufficient numbers of health physics specialists (HPSs) to fill authorizations has been a consistent struggle for the Army Medical Department due to the rigorous academic requirements of the additional skill identifier-producing program. This shortage has limited MOS 68SN4 deployment opportunities in the past and prevented medical planners from recognizing the capabilities these Soldiers can bring to the fight. In 2014, for the first time, HPSs were sourced to deploy as an augmentation capability to the 172nd Preventive Medicine Detachment (PM Det), the sole PM Det supporting the Combined Joint Operations Area-Afghanistan. Considerable successes in bettering radiation safety practices and improvements in incident and accident response were achieved as a result of their deployment. The purposes of this article are to describe the mission services performed by HPSs in Afghanistan, discuss the benefits of deploying HPSs with PM Dets, and demonstrate to senior medical leadership the importance of maintaining a health physics capability in a theater environment. PMID- 26276952 TI - An estimate of the second-order in-plane acceleration sensitivity of a Y-cut quartz thickness-shear resonator. AB - We perform a theoretical analysis of the secondorder in-plane acceleration sensitivity of a Y-cut quartz thickness- shear mode resonator. The second-order nonlinear theory of elasticity for anisotropic crystals is used to determine the biasing fields in the resonator under in-plane acceleration. The acceleration induced frequency shift is determined from a perturbation analysis based on the plate equations for small-amplitude vibrations superposed on a finite bias. We show that, whereas the first-order acceleration-induced frequency shift is zero for a structurally symmetric resonator under in-plane acceleration, the second order frequency shift is nonzero and is quadratic in the acceleration. As the fourth-order nonlinear elastic constants of quartz have never been measured, we can only estimate the magnitude of the second-order frequency shift. For a particular case of interest, we find Deltaomega/omega0 ~ 10(-18), 10(-16), and 10(-14) when the acceleration is 1, 10, and 100 g, respectively. PMID- 26276951 TI - Human induced pluripotent stem cell-derived versus adult cardiomyocytes: an in silico electrophysiological study on effects of ionic current block. AB - BACKGROUND AND PURPOSE: Two new technologies are likely to revolutionize cardiac safety and drug development: in vitro experiments on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and in silico human adult ventricular cardiomyocyte (hAdultV-CM) models. Their combination was recently proposed as a potential replacement for the present hERG-based QT study for pharmacological safety assessments. Here, we systematically compared in silico the effects of selective ionic current block on hiPSC-CM and hAdultV-CM action potentials (APs), to identify similarities/differences and to illustrate the potential of computational models as supportive tools for evaluating new in vitro technologies. EXPERIMENTAL APPROACH: In silico AP models of ventricular-like and atrial-like hiPSC-CMs and hAdultV-CM were used to simulate the main effects of four degrees of block of the main cardiac transmembrane currents. KEY RESULTS: Qualitatively, hiPSC-CM and hAdultV-CM APs showed similar responses to current block, consistent with results from experiments. However, quantitatively, hiPSC CMs were more sensitive to block of (i) L-type Ca(2+) currents due to the overexpression of the Na(+) /Ca(2+) exchanger (leading to shorter APs) and (ii) the inward rectifier K(+) current due to reduced repolarization reserve (inducing diastolic potential depolarization and repolarization failure). CONCLUSIONS AND IMPLICATIONS: In silico hiPSC-CMs and hAdultV-CMs exhibit a similar response to selective current blocks. However, overall hiPSC-CMs show greater sensitivity to block, which may facilitate in vitro identification of drug-induced effects. Extrapolation of drug effects from hiPSC-CM to hAdultV-CM and pro-arrhythmic risk assessment can be facilitated by in silico predictions using biophysically-based computational models. PMID- 26276953 TI - A multiresolution approach to shear wave image reconstruction. AB - Shear wave imaging techniques build maps of local elasticity estimating the local group velocity of induced mechanical waves. Velocity estimates are formed using the time delay in the motion profile of the medium at two or more points offset from the shear wave source. Because the absolute time-of-flight between any pair of locations scales with the distance between them, there is an inherent trade off between robustness to time-of-flight errors and lateral spatial resolution based on the number and spacing of the receive points used for each estimate. This work proposes a method of using the time delays measured between all combinations of locations to estimate a noise-robust, high-resolution image. The time-of-flight problem is presented as an overdetermined system of linear equations that can be directly solved with and without spatial regularization terms. Finite element method simulations of acoustic radiation force-induced shear waves are used to illustrate the method, demonstrating superior contrast-to noise ratio and lateral edge resolution characteristics compared with linear regression of arrival times. This technique may improve shear wave imaging in situations where time-of-flight noise is a limiting factor. PMID- 26276954 TI - Plane wave compounding based on a joint transmitting-receiving adaptive beamformer. AB - Plane wave compounding is a useful mode for ultrasound imaging because it can make a good compromise between imaging quality and frame rate. It is also useful for broad view ultrasound imaging. Traditional coherent plane wave compounding coherently sums the echo data of different steered transmitting waves as the output. The data correlation information of different emissions is not considered. Therefore, some adaptive techniques can be introduced into the compounding procedure. In this paper, we propose a Joint Transmitting-Receiving (JTR) adaptive beamforming scheme for plane wave compounding. Unlike traditional adaptive beamformers, the proposed beamforming scheme is designed for the 2-D data set obtained from multiple plane wave firings. It calculates both the transmitting aperture weights and the receiving aperture weights and then combines them into a 2-D adaptive weight function for compounding. Experiments are conducted on both simulated and phantom data. Results show that the proposed scheme has better performance on both point targets and cysts than the existing plane wave compounding approach. Because of the adaptive process in both apertures for compounding, an improved resolution is observed in both simulation and phantom studies. When the eigenanalysis is introduced, a contrast enhancement is achieved. For the simulated cyst, a contrast ratio (CR) improvement of 48% is achieved compared with the traditional plane wave compounding. For the phantom cyst, this improvement is 213.8%. The proposed scheme also has good robustness against sound velocity errors. Therefore, it is effective in enhancing the coherent plane wave compounding quality. PMID- 26276955 TI - Frequency adaptation for enhanced radiation force amplitude in dynamic elastography. AB - In remote dynamic elastography, the amplitude of the generated displacement field is directly related to the amplitude of the radiation force. Therefore, displacement improvement for better tissue characterization requires the optimization of the radiation force amplitude by increasing the push duration and/or the excitation amplitude applied on the transducer. The main problem of these approaches is that the Food and Drug Administration (FDA) thresholds for medical applications and transducer limitations may be easily exceeded. In the present study, the effect of the frequency used for the generation of the radiation force on the amplitude of the displacement field was investigated. We found that amplitudes of displacements generated by adapted radiation force sequences were greater than those generated by standard nonadapted ones (i.e., single push acoustic radiation force impulse and supersonic shear imaging). Gains in magnitude were between 20 to 158% for in vitro measurements on agar-gelatin phantoms, and 170 to 336% for ex vivo measurements on a human breast sample, depending on focus depths and attenuations of tested samples. The signal-to-noise ratio was also improved more than 4-fold with adapted sequences. We conclude that frequency adaptation is a complementary technique that is efficient for the optimization of displacement amplitudes. This technique can be used safely to optimize the deposited local acoustic energy without increasing the risk of damaging tissues and transducer elements. PMID- 26276956 TI - 3-D ultrafast Doppler imaging applied to the noninvasive mapping of blood vessels in vivo. AB - Ultrafast Doppler imaging was introduced as a technique to quantify blood flow in an entire 2-D field of view, expanding the field of application of ultrasound imaging to the highly sensitive anatomical and functional mapping of blood vessels. We have recently developed 3-D ultrafast ultrasound imaging, a technique that can produce thousands of ultrasound volumes per second, based on a 3-D plane and diverging wave emissions, and demonstrated its clinical feasibility in human subjects in vivo. In this study, we show that noninvasive 3-D ultrafast power Doppler, pulsed Doppler, and color Doppler imaging can be used to perform imaging of blood vessels in humans when using coherent compounding of 3-D tilted plane waves. A customized, programmable, 1024-channel ultrasound system was designed to perform 3-D ultrafast imaging. Using a 32 * 32, 3-MHz matrix phased array (Vermon, Tours, France), volumes were beamformed by coherently compounding successive tilted plane wave emissions. Doppler processing was then applied in a voxel-wise fashion. The proof of principle of 3-D ultrafast power Doppler imaging was first performed by imaging Tygon tubes of various diameters, and in vivo feasibility was demonstrated by imaging small vessels in the human thyroid. Simultaneous 3-D color and pulsed Doppler imaging using compounded emissions were also applied in the carotid artery and the jugular vein in one healthy volunteer. PMID- 26276957 TI - Full 3-D transverse oscillations: a method for tissue motion estimation. AB - We present a new method to estimate 4-D (3-D + time) tissue motion. The method used combines 3-D phase based motion estimation with an unconventional beamforming strategy. The beamforming technique allows us to obtain full 3-D RF volumes with axial, lateral, and elevation modulations. Based on these images, we propose a method to estimate 3-D motion that uses phase images instead of amplitude images. First, volumes featuring 3-D oscillations are created using only a single apodization function, and the 3-D displacement between two consecutive volumes is estimated simultaneously by applying this 3-D estimation. The validity of the method is investigated by conducting simulations and phantom experiments. The results are compared with those obtained with two other conventional estimation methods: block matching and optical flow. The results show that the proposed method outperforms the conventional methods, especially in the transverse directions. PMID- 26276958 TI - Multi-frame elastography using a handheld force-controlled ultrasound probe. AB - We propose a new method for strain field estimation in quasi-static ultrasound elastography based on matching RF data frames of compressed tissues. The method benefits from using a handheld force-controlled ultrasound probe, which provides the contact force magnitude and therefore improves repeatability of displacement field estimation. The displacement field is estimated in a two-phase manner using triplets of RF data frames consisting of a pre-compression image and two post compression images obtained with lower and higher compression ratios. First, a reliable displacement field estimate is calculated for the first post-compression frame. Second, we use this displacement estimate to warp the second post compression frame while using linear elasticity to obtain an initial approximation. Final displacement estimation is refined using the warped image. The two-phase displacement estimation allows for higher compression ratios, thus increasing the practical resolution of the strain estimates. The strain field is computed from a displacement field using a smoothness- regularized energy functional, which takes into consideration local displacement estimation quality. The minimization is performed using an efficient primal-dual hybrid gradient algorithm, which can leverage the architecture of a graphical processing unit. The method is quantitatively evaluated using finite element simulations. We compute strain estimates for tissue-mimicking phantoms with known elastic properties and finally perform a qualitative validation using in vivo patient data. PMID- 26276959 TI - Nonlocal means filter-based speckle tracking. AB - The objective of sensorless freehand 3-D ultrasound imaging is to eliminate the need for additional tracking hardware and reduce cost and complexity. However, the accuracy of current out-of-plane pose estimation is main obstacle for full 6 degree-of-freedom (DoF) tracking. We propose a new filter-based speckle tracking framework to increase the accuracy of out-of-plane displacement estimation. In this framework, we use the displacement estimation not only for the specific speckle pattern, but for the entire image. We develop a nonlocal means (NLM) filter based on a probabilistic normal variance mixture model of ultrasound, known as Rician-inverse Gaussian (RiIG). To aggregate the local displacement estimations, Stein's unbiased risk estimate (SURE) is used as a quality measure of the estimations. We derive an explicit analytical form of SURE for the RiIG model and use it as a weight factor. The proposed filter-based speckle tracking framework is formulated and evaluated for three commonly used noise models, including the RiIG model. The out-of-plane estimations are compared with our previously proposed model-based algorithm in a set of ex vivo experiments for different tissue types. We show that the proposed RiIG filter-based method is more accurate and less tissue-dependent than the other methods. The proposed method is also evaluated in vivo on the spines of five different subjects to assess the feasibility of a clinical application. The 6-DoF transform parameters are estimated and compared with the electromagnetic tracker measurements. The results show higher tracking accuracy for typical small lateral displacements and tilt rotations between image pairs. PMID- 26276960 TI - Data-driven and calibration-free Lamb wave source localization with sparse sensor arrays. AB - Most Lamb wave localization techniques require that we know the wave's velocity characteristics; yet, in many practical scenarios, velocity estimates can be challenging to acquire, are unavailable, or are unreliable because of the complexity of Lamb waves. As a result, there is a significant need for new methods that can reduce a system's reliance on a priori velocity information. This paper addresses this challenge through two novel source localization methods designed for sparse sensor arrays in isotropic media. Both methods exploit the fundamental sparse structure of a Lamb wave's frequency-wavenumber representation. The first method uses sparse recovery techniques to extract velocities from calibration data. The second method uses kurtosis and the support earth mover's distance to measure the sparseness of a Lamb wave's approximate frequency-wavenumber representation. These measures are then used to locate acoustic sources with no prior calibration data. We experimentally study each method with a collection of acoustic emission data measured from a 1.22 m by 1.22 m isotropic aluminum plate. We show that both methods can achieve less than 1 cm localization error and have less systematic error than traditional time-of arrival localization methods. PMID- 26276961 TI - Nonintrusive estimation of anisotropic stiffness maps of heterogeneous steel welds for the improvement of ultrasonic array inspection. AB - It is challenging to inspect austenitic welds nondestructively using ultrasonic waves because the spatially varying elastic anisotropy of weld microstructures can lead to the deviation of ultrasound. Models have been developed to predict the propagation of ultrasound in such welds once the weld stiffness heterogeneity is known. Consequently, it is desirable to have a means of measuring the variation in elastic anisotropy experimentally so as to be able to correct for deviations in ultrasonic pathways for the improvement of weld inspection. This paper investigates the use of external nonintrusive ultrasonic array measurements to construct such weld stiffness maps, representing the orientation of the stiffness tensor according to location in the weld cross section. An inverse model based on a genetic algorithm has been developed to recover a small number of key parameters in an approximate model of the weld map, making use of ultrasonic array measurements. The approximate model of the weld map uses the Modeling of anIsotropy based on Notebook of Arcwelding (MINA) formulation, which is one of the representations that has been proposed by other researchers to provide a simple, yet physically based, description of the overall variations of orientations of the stiffness tensors over the weld cross section. The choice of sensitive ultrasonic modes as well as the best monitoring positions have been discussed to achieve a robust inversion. Experiments have been carried out on a 60-mm-thick multipass tungsten inert gas (TIG) weld to validate the findings of the modeling, showing very good agreement. This work shows that ultrasonic array measurements can be used on a single side of a butt-welded plate, such that there is no need to access the remote side, to construct an approximate but useful weld map of the spatial variations in anisotropic stiffness orientation that occur within the weld. PMID- 26276962 TI - Experimental study of passive defect localization in plates using ambient noise. AB - Passive listening methodology has been shown to be a practical and effective method for passive structural health monitoring. In this work, this approach is applied experimentally to monitor the occurrence of defects in thin aluminum plates. A correlation matrix is estimated from noise vibrations recorded on a transducer array. A defect is localized by applying a beamforming algorithm to the difference between the correlation matrices obtained with and without the defect. We successfully detect defects for different kinds of noise sources. Moreover, we show that this technique is robust to detect massive inclusions, holes, and cracks. With a vibrometer, we observe that the fidelity of the estimated transient responses strongly depends on the number of uncorrelated noise sources. Finally, we show that the defect is successfully localized even if the noise source distribution is not uniform, provided that it remains spatially stationary between the states with and without defect. A simple theoretical framework is proposed to interpret these results. PMID- 26276963 TI - Bulk mode piezoresistive thermal oscillators: time constants and scaling. AB - This paper presents design and analysis for engineering the thermal and mechanical time constants of piezoresistive thermal oscillators. The optimal design is obtained by minimizing the threshold current density required to initiate self-sustained oscillations. Optimizing the oscillator geometry is of extreme practical importance given that the threshold current densities (GA/m(2)) are close to the breakdown current densities observed in silicon. The equivalent circuit model of the oscillator is used along with the lumped thermal, mechanical, and piezoresistive parameters to calculate the threshold current density of the oscillator. The optimal ratio of the thermal and mechanical time constants is found to be ?3 for bulkmode oscillators where the in-plane dimensions control the mechanical resonant frequency. The final frequency of oscillations is obtained as a function of the mechanical resonant frequency, quality factor (Q), and the ratio of the time constants. Results show that scaling the dimension (or frequency) has a weak sub-linear effect on the oscillator performance. Finally, we compare different bulk modes, based on the calculated threshold dc currents for a 1-GHz oscillator. PMID- 26276964 TI - The Endothelial-mesenchymal Transition in Systemic Sclerosis Is Induced by Endothelin-1 and Transforming Growth Factor-beta and May Be Blocked by Macitentan, a Dual Endothelin-1 Receptor Antagonist. AB - OBJECTIVE: High endothelin-1 (ET-1) and transforming growth factor-beta (TGF beta) levels may induce in healthy endothelial cells (EC) an endothelial-to mesenchymal transition (EndMT). The same cytokines are associated with fibrosis development in systemic sclerosis (SSc). Although EndMT has not been definitively shown in SSc, this process, potentially induced by a stimulatory loop involving these 2 cytokines, overexpressed in this disease might contribute to fibroblast accumulation in affected tissues. Macitentan (MAC), an ET-1 receptor antagonist interfering with this loop, might prevent EndMT and fibroblast accumulation. METHODS: EC, isolated from healthy controls (HC) and patients with SSc, were treated with ET-1 and TGF-beta and successively analyzed for gene and protein expressions of endothelial and mesenchymal markers, and for Sma- and Mad-related (SMAD) phosphorylation. Further, in the supernatants, we evaluated ET-1 and TGF beta production by ELISA assay. In each assay we evaluated the ability of MAC to inhibit both the TGF-beta and ET-1 effects. RESULTS: We showed that both TGF-beta and ET-1 treatments induced an activation of the EndMT process in SSc-EC as reported in HC cells. The ELISA assays showed a mutual TGF-beta and ET-1 induction in both SSc-EC and HC-EC. A statistically significant increase of SMAD phosphorylation after treatment was observed in SSc-EC. In each assay, MAC inhibited both TGF-beta and ET-1 effects. CONCLUSION: Our work is the first demonstration in literature that SSc-EC, under the synergistic effect of TGF-beta and ET-1, may transdifferentiate toward myofibroblasts, thus contributing to fibroblast accumulation. MAC, interfering with this process in vitro, may offer a new potential therapeutic strategy against fibrosis. PMID- 26276965 TI - Longterm Safety of Rituximab: Final Report of the Rheumatoid Arthritis Global Clinical Trial Program over 11 Years. AB - OBJECTIVE: Final evaluation of the longterm safety of rituximab (RTX) in rheumatoid arthritis (RA) up to 11 years. METHODS: Pooled observed case analysis of data from patients with moderate to severe, active RA in a global clinical trial program. RESULTS: As of September 2012, 3595 patients received a mean of 4 courses (range 1-20) of RTX over 11 years [14,816 patient-years (PY)]. Of these, 1246 patients had > 5 years of followup (8970 PY). A pooled placebo population (n = 818) was included in the analysis. The overall serious infection event (SIE) rate was 3.76/100 PY (2.71/100 PY in patients observed for > 5 yrs) and comparable with rates reported previously at 9.5 years (3.94/100 PY and 3.26/100 PY, respectively). SIE rates continued to be similar before and during/after development of low immunoglobulin levels, and serious opportunistic infections remained rare. Rates of cardiac events remained consistent with previous analysis and with rates in the general RA population. No increased risk of malignancy over time was observed. CONCLUSION: This final report demonstrates that RTX remains well tolerated over time and multiple courses. No new safety risks were identified and there was no increase in the rate of any types of adverse events with prolonged exposure to RTX during 11 years of observation. PMID- 26276966 TI - Alemtuzumab as Remission Induction Therapy in Behcet Disease: A 20-year Experience. AB - OBJECTIVE: To study the efficacy and safety of anti-CD52 antibody (alemtuzumab) in the treatment of refractory and relapsing Behcet disease (BD). METHODS: Thirty two patients (22 women) with BD received 60 courses of alemtuzumab between 1994 and 2013. Three-dose regimens were used: 134 mg in 21 courses (Group 1), 95 mg in 18 courses (Group 2), and 60 mg in 21 courses (Group 3). Immunosuppressive drugs were stopped at the time of alemtuzumab, and prednisolone was reduced according to clinical response. Treatment response was assessed by clinical status, inflammatory activity, prednisolone dose, and the need for subsequent immunosuppressive drugs and disease relapse. RESULTS: After the first alemtuzumab course, 27 of 32 patients (84%) achieved partial or complete remission (CR). Fifty of 60 courses (83%) resulted in remission (66% CR) without differences in remission rates between dosing regimens. Profound lymphocyte depletion occurred after all courses. Relapse-free survival rates were 83.6% at 6 months and 52.8% at 12 months, and were higher among Group 1 patients (Group 1: 100% and 77.8%, Group 2: 81.3% and 37.5%, and Group 3: 65.0% and 37.1%, p < 0.001). Mild to moderate infusion reactions occurred after 16 courses (27%). Eight patients (25%) developed symptomatic thyroid disease. CONCLUSION: Alemtuzumab led to remission in the majority of patients with difficult-to-treat BD. Relapse was common and may be associated with lower dosing. Adverse events included infusion reactions and new autoimmunity. Achieving complete lymphocyte depletion did not affect the remission rate or duration. PMID- 26276967 TI - Relation of Autoimmune Cytopenia to Glandular and Systemic Manifestations in Primary Sjogren Syndrome: Analysis of 113 Korean Patients. AB - OBJECTIVE: To investigate the characteristics of patients with primary Sjogren syndrome (pSS) who have autoimmune cytopenia. METHODS: We analyzed 113 participants from the Korean Initiative of Primary Sjogren Syndrome, a prospective pSS cohort. Autoimmune cytopenia was defined as autoimmune origin neutropenia, anemia, and/or thrombocytopenia without vitamin or iron deficiency, or drug-induced cytopenia. To identify the association between autoimmune cytopenia and the clinical characteristics of pSS, extraglandular manifestations were analyzed according to the European League Against Rheumatism Sjogren's syndrome disease activity index (ESSDAI) definition. Xerophthalmia was assessed with the Ocular Surface Disease Index, Schirmer I test, ocular stain score (OSS), and tear film breakup time. RESULTS: The median total ESSDAI score was 2 (interquartile range 1-6). About a quarter of patients had no systemic activity. Autoimmune cytopenia was observed in 23.9% of patients (n = 27). Moderate biological features were more frequently observed in patients with autoimmune cytopenia than in patients without [10 (37%) and 11 (12.8%), respectively, p = 0.016]. Articular involvement was exhibited in 1 patient with autoimmune cytopenia, but in 23 patients (27.4%) without autoimmune cytopenia (p = 0.013). Higher OSS (p = 0.002) and lower mean Schirmer I test (p = 0.029) were observed in patients with autoimmune cytopenia than in those without. Neutrophils and lymphocytes negatively correlated with OSS (rho = -0.204, p = 0.041 and rho = 0.230, p = 0.020, respectively). CONCLUSION: Autoimmune cytopenia is closely associated with severe ocular surface damage in pSS. Therefore, assessment of xerophthalmia by ophthalmologists may be mandatory, particularly in patients with pSS with cytopenia, even if patients do not complain of eye dryness. PMID- 26276968 TI - Evaluation of Health Outcomes with Etanercept Treatment in Patients with Early Nonradiographic Axial Spondyloarthritis. AB - OBJECTIVE: Analyses were conducted to examine the baseline burden of illness and compare the effect of etanercept (ETN) versus placebo (PBO) on quality of life (QOL) in patients with nonradiographic axial spondyloarthritis (nr-axSpA) who failed nonsteroidal antiinflammatory drugs (NSAID). METHODS: Patients fulfilling the Assessment of Spondyloarthritis International Society axSpA criteria, not meeting the modified New York criteria for ankylosing spondylitis (AS), who were symptomatic 3 months to 5 years, with a Bath AS Disease Activity Index score >= 4, and failed >= 2 NSAID were randomized to ETN 50 mg weekly or PBO (double blind) for 12 weeks, followed by open-label ETN 50 mg for 92 weeks. Stable NSAID were allowed throughout our study. QOL outcomes over 24 weeks were analyzed using ANCOVA models. RESULTS: At baseline, Multidimensional Fatigue Inventory (MFI; ETN mean 14.7, PBO mean 15.0), EQ-5D utility (0.52, 0.57), EQ-5D visual analog scale (56.5, 56.4), and Medical Outcomes Study (MOS) Sleep Index II (45.5, 48.1) were worse than population norms (6.6-8.0, 0.86, 82.5, and 25.8, respectively). At Week 12, Bath AS Patient Global Score, nocturnal and average back pain, MOS Short Form-36 (SF-36) physical component, and Work Productivity and Activity Index (WPAI) presenteeism and activity impairment favored ETN (p < 0.05). Nonsignificant improvements for ETN were seen in other WPAI domains, MFI, MOS Sleep Index I and II, Hospital Anxiety and Depression Scale, EQ-5D utility score, and SF-36 mental component (p > 0.05). At Week 24, patients in the PBO group who had switched to ETN at Week 12 showed improvement in most QOL assessments, similar to that seen in patients receiving ETN for 24 weeks. CONCLUSION: Improvements favored ETN in QOL and productivity measures, with limited improvement on general QOL measures. Short disease duration, a short PBO controlled period, and a wide range of QOL scores at baseline may have influenced improvements. PMID- 26276969 TI - Association Between Infrapatellar Fat Pad Volume and Knee Structural Changes in Patients with Knee Osteoarthritis. AB - OBJECTIVE: The function of the infrapatellar fat pad (IPFP) in knee osteoarthritis (OA) remains uncertain. This study aimed to examine cross sectional associations between IPFP volume and knee structures in patients with knee OA. METHODS: The study included 174 patients with clinical knee OA (mean age, 55.5 yrs). Fat-suppressed 3-D T1-weighted spoiled gradient recall magnetic resonance imaging (MRI) was used to measure the IPFP and cartilage volume. T2 weighted fast spin echo MRI was used to assess cartilage defects and bone marrow lesions (BML). Radiographic knee osteophytes and joint space narrowing (JSN) were assessed using the Osteoarthritis Research Society International atlas. RESULTS: After adjustment for potential confounders, greater IPFP volume was associated with greater tibial and patellar cartilage volume (all p < 0.05), and fewer cartilage defects at all sites (OR 0.88-0.91, all p < 0.05). IPFP volume was associated with presence of BML at lateral tibial and medial femoral sites (OR 0.88-0.91, all p < 0.05) and osteophytes at lateral tibiofemoral compartment (OR 0.88, p < 0.05). IPFP volume was not significantly associated with JSN. CONCLUSION: Greater IPFP volume was associated with greater knee cartilage volume and fewer structural abnormalities, suggesting a protective role of IPFP size in knee OA. PMID- 26276970 TI - The Spirit of OMERACT: Q Methodology Analysis of Conference Characteristics Valued by Delegates. AB - OBJECTIVE: To identify the major features of OMERACT meetings as valued by frequent participants and to explore whether there are groups of participants with different opinions. METHODS: Using Q methodology (a qualitative and quantitative approach to grouping people according to subjective opinion), participants (who attended more than 1 OMERACT conference) sorted 66 statements relating to the "spirit of OMERACT" according to level of agreement across a normal distribution grid. Data were examined using Q factor analysis. RESULTS: Of 226 potential participants, 105 responded (46%). All participants highly ranked the focus on global standardization of methods, outcome measures, data-driven research, methodological discussion, and international collaboration. Four factors describing the "spirit of OMERACT" were identified: "Evidence not eminence" (n = 31) valued the data- and evidence-driven research above personality and status; "Collaboration and collegiality" (n = 19) valued the international and cross-stakeholder collaboration, interaction, and collegiality; "Equal voices, equal votes, common goals" (n = 12) valued equality in discussion and voting, with everyone striving toward the same goal; "principles and product, not process" (n = 8) valued the principles of focusing on outcome measures and the product of guiding clinical trials, but were unsure whether the process is necessary to reach this. The factors did not segregate different stakeholder groups. CONCLUSION: Delegates value different elements of OMERACT, and thus the "spirit of OMERACT" encompasses evidence-based research, collaboration, and equality, although a small group are unsure whether the process is necessary to achieve the end result. Q methodology may prove useful for conference organizers to identify their delegates' different needs to tailor conference content. PMID- 26276971 TI - Factor H Autoantibodies in Patients with Antiphospholipid Syndrome and Thrombosis. AB - OBJECTIVE: Autoantibodies to complement factor H (FH) are associated with atypical hemolytic uremic syndrome, but can also be detected in patients with rheumatoid arthritis and in patients positive for lupus anticoagulants and thus potentially antiphospholipid syndrome (APS). To our knowledge, no data are available on the association between the presence of FH autoantibodies in APS and clinical manifestations. METHODS: We determined FH autoantibody levels using ELISA in 2 cohorts of patients with primary (PAPS) and secondary APS (SAPS) from Serbia and Italy, and an additional cohort including patients with venous thromboembolism (VTE) from Sweden. RESULTS: FH autoantibodies were detected in 13.7% of patients (n = 73) with PAPS and 30.3% of patients (n = 33) with SAPS in the Serbian cohort. FH autoantibody frequency in the Italian cohort was 33.3% (n = 15) and 36% (n = 25) in PAPS and SAPS, respectively. Both FH autoantibody levels and frequencies observed in both APS cohorts were significantly higher than in matched healthy controls (5%). Further, patients with PAPS with venous thrombosis in the Serbian cohort had significantly higher levels of FH autoantibodies. Therefore, we analyzed a dedicated Swedish thrombosis cohort and found that patients with FH autoantibody positivity had higher risk of VTE recurrence (HR 2.0, 95% CI 1.2-3.3, p = 0.011) compared with the reference group of FH autoantibody-negative patients. CONCLUSION: Overall, the data indicate that in patients with APS and recurrent venous thrombosis, there are increased levels of FH autoantibodies, a finding associated with poor clinical outcome. PMID- 26276972 TI - Sleep parameters by actigraphy and relationship between plasma melatonin and intestinal permeability in alcoholics. PMID- 26276973 TI - Response to Dr. Kawada. PMID- 26276974 TI - Allergen-induced resistin-like molecule- promotes esophageal epithelial cell hyperplasia in eosinophilic esophagitis. PMID- 26276975 TI - Commentaries on Viewpoint: Why do some patients stop breathing after taking narcotics? Ventilatory chemosensitivity as a predictor of opioid-induced respiratory depression. PMID- 26276976 TI - Last Word on Viewpoint: Why do some patients stop breathing after taking narcotics? Ventilatory chemosensitivity as a predictor of opioid-induced respiratory depression. PMID- 26276977 TI - Victoria Cowling. AB - Victoria Cowling received her BA from the University of Cambridge. She completed her PhD with Julian Downward and Gerard Evan at Cancer Research UK in London, and then moved to the US for a postdoctoral position at Princeton University and Dartmouth College with Michael Cole. Since 2008, she has been running a lab at Dundee University. She is an MRC Senior Research Fellow, a Lister Institute Research Fellow and an EMBO Young Investigator and, in 2015, she was the first recipient of the Women in Cell Biology medal, awarded by the British Society for Cell Biology. PMID- 26276978 TI - Letter to the Editor: Giant proteins and cancer chemotherapy cardiotoxicity. PMID- 26276979 TI - A Robust Heart Rate Monitoring Scheme Using Photoplethysmographic Signals Corrupted by Intense Motion Artifacts. AB - GOAL: Although photoplethysmographic (PPG) signals can monitor heart rate (HR) quite conveniently in hospital environments, trying to incorporate them during fitness programs poses a great challenge, since in these cases, the signals are heavily corrupted by motion artifacts. METHODS: In this paper, we present a novel signal processing framework which utilizes two channel PPG signals and estimates HR in two stages. The first stage eliminates any chances of a runaway error by resorting to an absolute criterion condition based on ensemble empirical mode decomposition. This stage enables the algorithm to depend very little on the previously estimated HR values and to discard the need of an initial resting phase. The second stage, on the other hand, increases the algorithm's robustness against offtrack errors by using recursive least squares filters complemented with an additional novel technique, namely time-domain extraction. RESULTS: Using this framework, an average absolute error of 1.02 beat per minute (BPM) and standard deviation of 1.79 BPM are recorded for 12 subjects performing a run with peak velocities reaching as high as 15 km/h. CONCLUSION: The performance of this algorithm is found to be better than the other recently reported algorithms in this field such as TROIKA and JOSS. SIGNIFICANCE: This method is expected to greatly facilitate the presently available wearable gadgets in HR computation during various physical activities. PMID- 26276980 TI - Flexible Epineural Strip Electrode for Recording in Fine Nerves. AB - This paper demonstrates flexible epineural strip electrodes (FLESE) for recording from small nerves. Small strip-shaped FLESE enables us to easily and closely stick on various sized nerves for less damage in a nerve and optimal recording quality. In addition, in order to enhance the neural interface, the gold electrode contacts were coated with carbon nanotubes, which reduced the impedance of the electrodes. We used the FLESEs to record electrically elicited nerve signals (compound neural action potentials) from the sciatic nerve in rats. Bipolar and differential bipolar configurations for the recording were investigated to optimize the recording configuration of the FLESEs. The successful results from differential bipolar recordings showed that the total length of FLESEs could be further reduced, maintaining the maximum recording ability, which would be beneficial for recording in very fine nerves. Our results demonstrate that new concept of FLESEs could play an important role in electroceuticals in near future. PMID- 26276981 TI - Gastroesophageal Reflux Disease Diagnosis Using Hierarchical Heterogeneous Descriptor Fusion Support Vector Machine. AB - A new computer-aided diagnosis method is proposed to diagnose the gastroesophageal reflux disease (GERD) from endoscopic images of the esophageal gastric junction. To avoid the interferences of different endoscope devices and automatic camera white balance adjustment, heterogeneous descriptors computed from heterogeneous color models are used to represent endoscopic images. Instead of concatenating these descriptors to a super vector, a hierarchical heterogeneous descriptor fusion support vector machine (HHDF-SVM) framework is proposed to simultaneously apply heterogeneous descriptors for GERD diagnosis and overcome the curse of dimensionality problem. During validation, heterogeneous descriptors are extracted from test endoscopic images at first. The classification result is obtained by using HHDF-SVM with heterogeneous descriptors. As shown in the experiments, our method can automatically diagnose GERD without any manual selection of region of interest and achieve better accuracy compared to states-of-the-art methods. PMID- 26276982 TI - Subspace Regularized Sparse Multitask Learning for Multiclass Neurodegenerative Disease Identification. AB - The high feature-dimension and low sample-size problem is one of the major challenges in the study of computer-aided Alzheimer's disease (AD) diagnosis. To circumvent this problem, feature selection and subspace learning have been playing core roles in the literature. Generally, feature selection methods are preferable in clinical applications due to their ease for interpretation, but subspace learning methods can usually achieve more promising results. In this paper, we combine two different methodological approaches to discriminative feature selection in a unified framework. Specifically, we utilize two subspace learning methods, namely, linear discriminant analysis and locality preserving projection, which have proven their effectiveness in a variety of fields, to select class-discriminative and noise-resistant features. Unlike previous methods in neuroimaging studies that mostly focused on a binary classification, the proposed feature selection method is further applicable for multiclass classification in AD diagnosis. Extensive experiments on the Alzheimer's disease neuroimaging initiative dataset showed the effectiveness of the proposed method over other state-of-the-art methods. PMID- 26276983 TI - Evaluation of Ultrasound-Based Sensor to Monitor Respiratory and Nonrespiratory Movement and Timing in Infants. AB - GOAL: To describe and validate a noncontacting sensor that used reflected ultrasound to separately monitor respiratory, nonrespiratory, and caretaker movements of infants. METHODS: An in-phase and quadrature (I & Q) detection scheme provided adequate bandwidth, in conjunction with postdetection filtering, to separate the three types of movement. The respiratory output was validated by comparing it to the electrical activity of the diaphragm (Edi) obtained from an infant ventilator in 11 infants. The nonrespiratory movement output was compared to movement detected by miniature accelerometers attached to the wrists, ankles, and heads of seven additional infants. Caretaker movement was compared to visual observations annotated in the recordings. RESULTS: The respiratory rate determined by the sensor was equivalent to that from the Edi signal. The sensor could detect the onset of inspiration significantly earlier than the Edi signal (23+/-69 ms). Nonrespiratory movement was identified with an agreement of 0.9 with the accelerometers. It potentially interfered with the respiratory output an average of 4.7+/-4.5% and 14.9+/15% of the time in infants not requiring or on ventilatory support, respectively. Caretaker movements were identified with 98% sensitivity and specificity. The sensor outputs were independent of body coverings or position. CONCLUSION: This single, noncontacting sensor can independently quantify these three types of movement. SIGNIFICANCE: It is feasible to use the sensor as trigger for synchronizing mechanical ventilators to spontaneous breathing, to quantify overall movement, to determine sleep state, to detect seizures, and to document the amount and effects of caretaker activity in infants. PMID- 26276984 TI - Optimization of Active Muscle Force-Length Models Using Least Squares Curve Fitting. AB - The objective of this paper is to propose an asymmetric Gaussian function as an alternative to the existing active force-length models, and to optimize this model along with several other existing models by using the least squares curve fitting method. The minimal set of coefficients is identified for each of these models to facilitate the least squares curve fitting. Sarcomere simulated data and one set of rabbits extensor digitorum II experimental data are used to illustrate optimal curve fitting of the selected force-length functions. The results shows that all the curves fit reasonably well with the simulated and experimental data, while the Gordon-Huxley-Julian model and asymmetric Gaussian function are better than other functions in terms of statistical test scores root mean squared error and R-squared. However, the differences in RMSE scores are insignificant (0.3-6%) for simulated data and (0.2-5%) for experimental data. The proposed asymmetric Gaussian model and the method of parametrization of this and the other force-length models mentioned above can be used in the studies on active force-length relationships of skeletal muscles that generate forces to cause movements of human and animal bodies. PMID- 26276985 TI - Utility of AdaBoost to Detect Sleep Apnea-Hypopnea Syndrome From Single-Channel Airflow. AB - GOAL: The purpose of this study is to evaluate the usefulness of the boosting algorithm AdaBoost (AB) in the context of the sleep apnea-hypopnea syndrome (SAHS) diagnosis. METHODS: We characterize SAHS in single-channel airflow (AF) signals from 317 subjects by the extraction of spectral and nonlinear features. Relevancy and redundancy analyses are conducted through the fast correlation based filter to derive the optimum set of features among them. These are used to feed classifiers based on linear discriminant analysis (LDA) and classification and regression trees (CART). LDA and CART models are sequentially obtained through AB, which combines their performances to reach higher diagnostic ability than each of them separately. RESULTS: Our AB-LDA and AB-CART approaches showed high diagnostic performance when determining SAHS and its severity. The assessment of different apnea-hypopnea index cutoffs using an independent test set derived into high accuracy: 86.5% (5 events/h), 86.5% (10 events/h), 81.0% (15 events/h), and 83.3% (30 events/h). These results widely outperformed those from logistic regression and a conventional event-detection algorithm applied to the same database. CONCLUSION: Our results suggest that AB applied to data from single-channel AF can be useful to determine SAHS and its severity. SIGNIFICANCE: SAHS detection might be simplified through the only use of single-channel AF data. PMID- 26276987 TI - Unsupervised Joint Feature Learning and Encoding for RGB-D Scene Labeling. AB - Most existing approaches for RGB-D indoor scene labeling employ hand-crafted features for each modality independently and combine them in a heuristic manner. There has been some attempt on directly learning features from raw RGB-D data, but the performance is not satisfactory. In this paper, we propose an unsupervised joint feature learning and encoding (JFLE) framework for RGB-D scene labeling. The main novelty of our learning framework lies in the joint optimization of feature learning and feature encoding in a coherent way, which significantly boosts the performance. By stacking basic learning structure, higher level features are derived and combined with lower level features for better representing RGB-D data. Moreover, to explore the nonlinear intrinsic characteristic of data, we further propose a more general joint deep feature learning and encoding (JDFLE) framework that introduces the nonlinear mapping into JFLE. The experimental results on the benchmark NYU depth dataset show that our approaches achieve competitive performance, compared with the state-of-the art methods, while our methods do not need complex feature handcrafting and feature combination and can be easily applied to other data sets. PMID- 26276986 TI - EEG Source Imaging Enhances the Decoding of Complex Right-Hand Motor Imagery Tasks. AB - GOAL: Sensorimotor-based brain-computer interfaces (BCIs) have achieved successful control of real and virtual devices in up to three dimensions; however, the traditional sensor-based paradigm limits the intuitive use of these systems. Many control signals for state-of-the-art BCIs involve imagining the movement of body parts that have little to do with the output command, revealing a cognitive disconnection between the user's intent and the action of the end effector. Therefore, there is a need to develop techniques that can identify with high spatial resolution the self-modulated neural activity reflective of the actions of a helpful output device. METHODS: We extend previous EEG source imaging (ESI) work to decoding natural hand/wrist manipulations by applying a novel technique to classifying four complex motor imaginations of the right hand: flexion, extension, supination, and pronation. RESULTS: We report an increase of up to 18.6% for individual task classification and 12.7% for overall classification using the proposed ESI approach over the traditional sensor-based method. CONCLUSION: ESI is able to enhance BCI performance of decoding complex right-hand motor imagery tasks. SIGNIFICANCE: This study may lead to the development of BCI systems with naturalistic and intuitive motor imaginations, thus facilitating broad use of noninvasive BCIs. PMID- 26276988 TI - Face Spoofing Detection Through Visual Codebooks of Spectral Temporal Cubes. AB - Despite important recent advances, the vulnerability of biometric systems to spoofing attacks is still an open problem. Spoof attacks occur when impostor users present synthetic biometric samples of a valid user to the biometric system seeking to deceive it. Considering the case of face biometrics, a spoofing attack consists in presenting a fake sample (e.g., photograph, digital video, or even a 3D mask) to the acquisition sensor with the facial information of a valid user. In this paper, we introduce a low cost and software-based method for detecting spoofing attempts in face recognition systems. Our hypothesis is that during acquisition, there will be inevitable artifacts left behind in the recaptured biometric samples allowing us to create a discriminative signature of the video generated by the biometric sensor. To characterize these artifacts, we extract time-spectral feature descriptors from the video, which can be understood as a low-level feature descriptor that gathers temporal and spectral information across the biometric sample and use the visual codebook concept to find mid-level feature descriptors computed from the low-level ones. Such descriptors are more robust for detecting several kinds of attacks than the low-level ones. The experimental results show the effectiveness of the proposed method for detecting different types of attacks in a variety of scenarios and data sets, including photos, videos, and 3D masks. PMID- 26276989 TI - Dynamical System Approach for Edge Detection Using Coupled FitzHugh-Nagumo Neurons. AB - The prospect of emulating the impressive computational capabilities of biological systems has led to considerable interest in the design of analog circuits that are potentially implementable in very large scale integration CMOS technology and are guided by biologically motivated models. For example, simple image processing tasks, such as the detection of edges in binary and grayscale images, have been performed by networks of FitzHugh-Nagumo-type neurons using the reaction diffusion models. However, in these studies, the one-to-one mapping of image pixels to component neurons makes the size of the network a critical factor in any such implementation. In this paper, we develop a simplified version of the employed reaction-diffusion model in three steps. In the first step, we perform a detailed study to locate this threshold using continuous Lyapunov exponents from dynamical system theory. Furthermore, we render the diffusion in the system to be anisotropic, with the degree of anisotropy being set by the gradients of grayscale values in each image. The final step involves a simplification of the model that is achieved by eliminating the terms that couple the membrane potentials of adjacent neurons. We apply our technique to detect edges in data sets of artificially generated and real images, and we demonstrate that the performance is as good if not better than that of the previous methods without increasing the size of the network. PMID- 26276990 TI - Adaptive Skin Classification Using Face and Body Detection. AB - In this paper, we propose a skin classification method exploiting faces and bodies automatically detected in the image, to adaptively initialize individual ad hoc skin classifiers. Each classifier is initialized by a face and body couple or by a single face, if no reliable body is detected. Thus, the proposed method builds an ad hoc skin classifier for each person in the image, resulting in a classifier less dependent from changes in skin color due to tan levels, races, genders, and illumination conditions. The experimental results on a heterogeneous data set of labeled images show that our proposal outperforms the state-of-the art methods, and that this improvement is statistically significant. PMID- 26276991 TI - Non-Rigid Point Set Registration by Preserving Global and Local Structures. AB - In previous work on point registration, the input point sets are often represented using Gaussian mixture models and the registration is then addressed through a probabilistic approach, which aims to exploit global relationships on the point sets. For non-rigid shapes, however, the local structures among neighboring points are also strong and stable and thus helpful in recovering the point correspondence. In this paper, we formulate point registration as the estimation of a mixture of densities, where local features, such as shape context, are used to assign the membership probabilities of the mixture model. This enables us to preserve both global and local structures during matching. The transformation between the two point sets is specified in a reproducing kernel Hilbert space and a sparse approximation is adopted to achieve a fast implementation. Extensive experiments on both synthesized and real data show the robustness of our approach under various types of distortions, such as deformation, noise, outliers, rotation, and occlusion. It greatly outperforms the state-of-the-art methods, especially when the data is badly degraded. PMID- 26276992 TI - Bit-Scalable Deep Hashing With Regularized Similarity Learning for Image Retrieval and Person Re-Identification. AB - Extracting informative image features and learning effective approximate hashing functions are two crucial steps in image retrieval. Conventional methods often study these two steps separately, e.g., learning hash functions from a predefined hand-crafted feature space. Meanwhile, the bit lengths of output hashing codes are preset in the most previous methods, neglecting the significance level of different bits and restricting their practical flexibility. To address these issues, we propose a supervised learning framework to generate compact and bit scalable hashing codes directly from raw images. We pose hashing learning as a problem of regularized similarity learning. In particular, we organize the training images into a batch of triplet samples, each sample containing two images with the same label and one with a different label. With these triplet samples, we maximize the margin between the matched pairs and the mismatched pairs in the Hamming space. In addition, a regularization term is introduced to enforce the adjacency consistency, i.e., images of similar appearances should have similar codes. The deep convolutional neural network is utilized to train the model in an end-to-end fashion, where discriminative image features and hash functions are simultaneously optimized. Furthermore, each bit of our hashing codes is unequally weighted, so that we can manipulate the code lengths by truncating the insignificant bits. Our framework outperforms state-of-the-arts on public benchmarks of similar image search and also achieves promising results in the application of person re-identification in surveillance. It is also shown that the generated bit-scalable hashing codes well preserve the discriminative powers with shorter code lengths. PMID- 26276993 TI - A New Quaternion-Based Encryption Method for DICOM Images. AB - In this paper, a new quaternion-based lossless encryption technique for digital image and communication on medicine (DICOM) images is proposed. We have scrutinized and slightly modified the concept of the DICOM network to point out the best location for the proposed encryption scheme, which significantly improves speed of DICOM images encryption in comparison with those originally embedded into DICOM advanced encryption standard and triple data encryption standard algorithms. The proposed algorithm decomposes a DICOM image into two 8 bit gray-tone images in order to perform encryption. The algorithm implements Feistel network like the scheme proposed by Sastry and Kumar. It uses special properties of quaternions to perform rotations of data sequences in 3D space for each of the cipher rounds. The images are written as Lipschitz quaternions, and modular arithmetic was implemented for operations with the quaternions. A computer-based analysis has been carried out, and the obtained results are shown at the end of this paper. PMID- 26276994 TI - Measurement of Contact Behavior Including Slippage of Cuff When Using Wearable Physical Assistant Robot. AB - Continuous use of wearable robots can cause skin injuries beneath the cuffs of robots. To prevent such injuries, understanding the contact behavior of the cuff is important. Thus far, this contact behavior has not been studied because of the difficulty involved in measuring the slippage under the cuff. In this study, for the first time, the relative displacement, slippage, and interaction force and moment at the thigh cuff of a robot during sit-to-stand motion were measured using an instrumented cuff, which was developed for this purpose. The results indicated that the slippage and relative displacement under the cuff was uneven because of the rotation of the cuff, which suggests that the risk of skin injuries is different at different positions. Especially, the skin closer to the hip showed larger dynamism, with a maximum slippage of approximately 10 mm and a displacement of 20 mm during motion. Another important phenomenon was the individual difference among subjects. During motion, the interaction force, moment, and slippage of some subjects suddenly increased. Such behavior results in stress concentration, which increases the risk of skin injuries. These analyses are intended to understand how skin injuries are caused and to design measures to prevent such injuries. PMID- 26276995 TI - Quaternion Singular Spectrum Analysis of Electroencephalogram With Application in Sleep Analysis. AB - A novel quaternion-valued singular spectrum analysis (SSA) is introduced for multichannel analysis of electroencephalogram (EEG). The analysis of EEG typically requires the decomposition of data channels into meaningful components despite the notoriously noisy nature of EEG--which is the aim of SSA. However, the singular value decomposition involved in SSA implies the strict orthogonality of the decomposed components, which may not reflect accurately the sources which exhibit similar neural activities. To allow for the modelling of such co-channel coupling, the quaternion domain is considered for the first time to formulate the SSA using the augmented statistics. As an application, we demonstrate how the augmented quaternion-valued SSA (AQSSA) can be used to extract the sources, even at a signal-to-noise ratio as low as -10 dB. To illustrate the usefulness of our quaternion-valued SSA in a rehabilitation setting, we employ the proposed SSA for sleep analysis to extract statistical descriptors for five-stage classification (Awake, N1, N2, N3 and REM). The level of agreement using these descriptors was 74% as quantified by the Cohen's kappa. PMID- 26276996 TI - The Principle of the Micro-Electronic Neural Bridge and a Prototype System Design. AB - The micro-electronic neural bridge (MENB) aims to rebuild lost motor function of paralyzed humans by routing movement-related signals from the brain, around the damage part in the spinal cord, to the external effectors. This study focused on the prototype system design of the MENB, including the principle of the MENB, the neural signal detecting circuit and the functional electrical stimulation (FES) circuit design, and the spike detecting and sorting algorithm. In this study, we developed a novel improved amplitude threshold spike detecting method based on variable forward difference threshold for both training and bridging phase. The discrete wavelet transform (DWT), a new level feature coefficient selection method based on Lilliefors test, and the k-means clustering method based on Mahalanobis distance were used for spike sorting. A real-time online spike detecting and sorting algorithm based on DWT and Euclidean distance was also implemented for the bridging phase. Tested by the data sets available at Caltech, in the training phase, the average sensitivity, specificity, and clustering accuracies are 99.43%, 97.83%, and 95.45%, respectively. Validated by the three fold cross-validation method, the average sensitivity, specificity, and classification accuracy are 99.43%, 97.70%, and 96.46%, respectively. PMID- 26276997 TI - Hardware-Algorithms Co-Design and Implementation of an Analog-to-Information Converter for Biosignals Based on Compressed Sensing. AB - We report the design and implementation of an Analog-to-Information Converter (AIC) based on Compressed Sensing (CS). The system is realized in a CMOS 180 nm technology and targets the acquisition of bio-signals with Nyquist frequency up to 100 kHz. To maximize performance and reduce hardware complexity, we co-design hardware together with acquisition and reconstruction algorithms. The resulting AIC outperforms previously proposed solutions mainly thanks to two key features. First, we adopt a novel method to deal with saturations in the computation of CS measurements. This allows no loss in performance even when 60% of measurements saturate. Second, the system is able to adapt itself to the energy distribution of the input by exploiting the so-called rakeness to maximize the amount of information contained in the measurements. With this approach, the 16 measurement channels integrated into a single device are expected to allow the acquisition and the correct reconstruction of most biomedical signals. As a case study, measurements on real electrocardiograms (ECGs) and electromyograms (EMGs) show signals that these can be reconstructed without any noticeable degradation with a compression rate, respectively, of 8 and 10. PMID- 26276998 TI - Designing Media for Visually-Impaired Users of Refreshable Touch Displays: Possibilities and Pitfalls. AB - This paper discusses issues of importance to designers of media for visually impaired users. The paper considers the influence of human factors on the effectiveness of presentation as well as the strengths and weaknesses of tactile, vibrotactile, haptic, and multimodal methods of rendering maps, graphs, and models. The authors, all of whom are visually impaired researchers in this domain, present findings from their own work and work of many others who have contributed to the current understanding of how to prepare and render images for both hard-copy and technology-mediated presentation of Braille and tangible graphics. PMID- 26276999 TI - Volume Haptics with Topology-Consistent Isosurfaces. AB - Haptic interfaces offer an intuitive way to interact with and manipulate 3D datasets, and may simplify the interpretation of visual information. This work proposes an algorithm to provide haptic feedback directly from volumetric datasets, as an aid to regular visualization. The haptic rendering algorithm lets users perceive isosurfaces in volumetric datasets, and it relies on several design features that ensure a robust and efficient rendering. A marching tetrahedra approach enables the dynamic extraction of a piecewise linear continuous isosurface. Robustness is achieved using a continuous collision detection step coupled with state-of-the-art proxy-based rendering methods over the extracted isosurface. The introduced marching tetrahedra approach guarantees that the extracted isosurface will match the topology of an equivalent isosurface computed using trilinear interpolation. The proposed haptic rendering algorithm improves the consistency between haptic and visual cues computing a second proxy on the isosurface displayed on screen. Our experiments demonstrate the improvements on the isosurface extraction stage as well as the robustness and the efficiency of the complete algorithm. PMID- 26277000 TI - Multistability and Instability of Neural Networks With Discontinuous Nonmonotonic Piecewise Linear Activation Functions. AB - In this paper, we discuss the coexistence and dynamical behaviors of multiple equilibrium points for recurrent neural networks with a class of discontinuous nonmonotonic piecewise linear activation functions. It is proved that under some conditions, such n -neuron neural networks can have at least 5(n) equilibrium points, 3(n) of which are locally stable and the others are unstable, based on the contraction mapping theorem and the theory of strict diagonal dominance matrix. The investigation shows that the neural networks with the discontinuous activation functions introduced in this paper can have both more total equilibrium points and more locally stable equilibrium points than the ones with continuous Mexican-hat-type activation function or discontinuous two-level activation functions. An illustrative example with computer simulations is presented to verify the theoretical analysis. PMID- 26277001 TI - On the Performance of Manhattan Nonnegative Matrix Factorization. AB - Extracting low-rank and sparse structures from matrices has been extensively studied in machine learning, compressed sensing, and conventional signal processing, and has been widely applied to recommendation systems, image reconstruction, visual analytics, and brain signal processing. Manhattan nonnegative matrix factorization (MahNMF) is an extension of the conventional NMF, which models the heavy-tailed Laplacian noise by minimizing the Manhattan distance between a nonnegative matrix X and the product of two nonnegative low rank factor matrices. Fast algorithms have been developed to restore the low-rank and sparse structures of X in the MahNMF. In this paper, we study the statistical performance of the MahNMF in the frame of the statistical learning theory. We decompose the expected reconstruction error of the MahNMF into the estimation error and the approximation error. The estimation error is bounded by the generalization error bounds of the MahNMF, while the approximation error is analyzed using the asymptotic results of the minimum distortion of vector quantization. The generalization error bound is valuable for determining the size of the training sample needed to guarantee a desirable upper bound for the defect between the expected and empirical reconstruction errors. Statistical performance analysis shows how the reduced dimensionality affects the estimation and approximation errors. Our framework can also be used for analyzing the performance of the NMF. PMID- 26277002 TI - Intelligent Tracking Control for a Class of Uncertain High-Order Nonlinear Systems. AB - This brief is concerned with the problem of intelligent tracking control for a class of high-order nonlinear systems with completely unknown nonlinearities. An intelligent adaptive control algorithm is presented by combining the adaptive backstepping technique with the neural networks' approximation ability. It is shown that the practical output tracking performance of the system is achieved using the proposed state-feedback controller under two mild assumptions. In particular, by introducing a parameter in the derivations, the tracking error between the time-varying target signal and the output can be reduced via tuning the controller design parameters. Moreover, in order to solve the problem of overparameterization, which is a common issue in adaptive control design, a controller with one adaptive law is also designed. Finally, simulation results are given to show the effectiveness of the theoretical approaches and the potential of the proposed new design techniques. PMID- 26277003 TI - Finite-Time Stabilizability and Instabilizability of Delayed Memristive Neural Networks With Nonlinear Discontinuous Controller. AB - This paper is concerned about the finite-time stabilizability and instabilizability for a class of delayed memristive neural networks (DMNNs). Through the design of a new nonlinear controller, algebraic criteria based on M matrix are established for the finite-time stabilizability of DMNNs, and the upper bound of the settling time for stabilization is estimated. In addition, finite-time instabilizability algebraic criteria are also established by choosing different parameters of the same nonlinear controller. The effectiveness and the superiority of the obtained results are supported by numerical simulations. PMID- 26277004 TI - Efficient Implementation of the Backpropagation Algorithm in FPGAs and Microcontrollers. AB - The well-known backpropagation learning algorithm is implemented in a field programmable gate array (FPGA) board and a microcontroller, focusing in obtaining efficient implementations in terms of a resource usage and computational speed. The algorithm was implemented in both cases using a training/validation/testing scheme in order to avoid overfitting problems. For the case of the FPGA implementation, a new neuron representation that reduces drastically the resource usage was introduced by combining the input and first hidden layer units in a single module. Further, a time-division multiplexing scheme was implemented for carrying out product computations taking advantage of the built-in digital signal processor cores. In both implementations, the floating-point data type representation normally used in a personal computer (PC) has been changed to a more efficient one based on a fixed-point scheme, reducing system memory variable usage and leading to an increase in computation speed. The results show that the modifications proposed produced a clear increase in computation speed in comparison with the standard PC-based implementation, demonstrating the usefulness of the intrinsic parallelism of FPGAs in neurocomputational tasks and the suitability of both implementations of the algorithm for its application to the real world problems. PMID- 26277005 TI - Semisupervised Support Vector Machines With Tangent Space Intrinsic Manifold Regularization. AB - Semisupervised learning has been an active research topic in machine learning and data mining. One main reason is that labeling examples is expensive and time consuming, while there are large numbers of unlabeled examples available in many practical problems. So far, Laplacian regularization has been widely used in semisupervised learning. In this paper, we propose a new regularization method called tangent space intrinsic manifold regularization. It is intrinsic to data manifold and favors linear functions on the manifold. Fundamental elements involved in the formulation of the regularization are local tangent space representations, which are estimated by local principal component analysis, and the connections that relate adjacent tangent spaces. Simultaneously, we explore its application to semisupervised classification and propose two new learning algorithms called tangent space intrinsic manifold regularized support vector machines (TiSVMs) and tangent space intrinsic manifold regularized twin SVMs (TiTSVMs). They effectively integrate the tangent space intrinsic manifold regularization consideration. The optimization of TiSVMs can be solved by a standard quadratic programming, while the optimization of TiTSVMs can be solved by a pair of standard quadratic programmings. The experimental results of semisupervised classification problems show the effectiveness of the proposed semisupervised learning algorithms. PMID- 26277006 TI - Enhanced Data-Driven Optimal Terminal ILC Using Current Iteration Control Knowledge. AB - In this paper, an enhanced data-driven optimal terminal iterative learning control (E-DDOTILC) is proposed for a class of nonlinear and nonaffine discrete time systems. A dynamical linearization approach is first developed with iterative operation points to formulate the relationship of system output and input into a linear affine form. Then, an ILC law is constructed with a nonlinear learning gain, which is a function about the system partial derivative with respect to the time-varying control input. In addition, a parameter updating law is designed to estimate the unknown partial derivatives iteratively. The input signals of the proposed E-DDOTILC are time-varying and updated utilizing not only the terminal tracking error of the previous run but also the input signals of the previous time instants in the current iteration. The proposed approach is a data driven control strategy and only the I/O data are required for the controller design and analysis. The monotonic convergence and effectiveness of the proposed approach is further verified by both the rigorous mathematical analysis and the simulation results. PMID- 26277007 TI - Data-Driven Hinfinity Control for Nonlinear Distributed Parameter Systems. AB - The data-driven Hinfinity control problem of nonlinear distributed parameter systems is considered in this paper. An off-policy learning method is developed to learn the Hinfinity control policy from real system data rather than the mathematical model. First, Karhunen-Loeve decomposition is used to compute the empirical eigenfunctions, which are then employed to derive a reduced-order model (ROM) of slow subsystem based on the singular perturbation theory. The Hinfinity control problem is reformulated based on the ROM, which can be transformed to solve the Hamilton-Jacobi-Isaacs (HJI) equation, theoretically. To learn the solution of the HJI equation from real system data, a data-driven off-policy learning approach is proposed based on the simultaneous policy update algorithm and its convergence is proved. For implementation purpose, a neural network (NN)- based action-critic structure is developed, where a critic NN and two action NNs are employed to approximate the value function, control, and disturbance policies, respectively. Subsequently, a least-square NN weight-tuning rule is derived with the method of weighted residuals. Finally, the developed data-driven off-policy learning approach is applied to a nonlinear diffusion-reaction process, and the obtained results demonstrate its effectiveness. PMID- 26277008 TI - Manifold Ranking-Based Matrix Factorization for Saliency Detection. AB - Saliency detection is used to identify the most important and informative area in a scene, and it is widely used in various vision tasks, including image quality assessment, image matching, and object recognition. Manifold ranking (MR) has been used to great effect for the saliency detection, since it not only incorporates the local spatial information but also utilizes the labeling information from background queries. However, MR completely ignores the feature information extracted from each superpixel. In this paper, we propose an MR-based matrix factorization (MRMF) method to overcome this limitation. MRMF models the ranking problem in the matrix factorization framework and embeds query sample labels in the coefficients. By incorporating spatial information and embedding labels, MRMF enforces similar saliency values on neighboring superpixels and ranks superpixels according to the learned coefficients. We prove that the MRMF has good generalizability, and develops an efficient optimization algorithm based on the Nesterov method. Experiments using popular benchmark data sets illustrate the promise of MRMF compared with the other state-of-the-art saliency detection methods. PMID- 26277009 TI - The Application of Visual Saliency Models in Objective Image Quality Assessment: A Statistical Evaluation. AB - Advances in image quality assessment have shown the potential added value of including visual attention aspects in its objective assessment. Numerous models of visual saliency are implemented and integrated in different image quality metrics (IQMs), but the gain in reliability of the resulting IQMs varies to a large extent. The causes and the trends of this variation would be highly beneficial for further improvement of IQMs, but are not fully understood. In this paper, an exhaustive statistical evaluation is conducted to justify the added value of computational saliency in objective image quality assessment, using 20 state-of-the-art saliency models and 12 best-known IQMs. Quantitative results show that the difference in predicting human fixations between saliency models is sufficient to yield a significant difference in performance gain when adding these saliency models to IQMs. However, surprisingly, the extent to which an IQM can profit from adding a saliency model does not appear to have direct relevance to how well this saliency model can predict human fixations. Our statistical analysis provides useful guidance for applying saliency models in IQMs, in terms of the effect of saliency model dependence, IQM dependence, and image distortion dependence. The testbed and software are made publicly available to the research community. PMID- 26277010 TI - Adaptive Neural Control for a Class of Pure-Feedback Nonlinear Systems via Dynamic Surface Technique. AB - This brief addresses the adaptive control problem for a class of pure-feedback systems with nonaffine functions possibly being nondifferentiable. Without using the mean value theorem, the difficulty of the control design for pure-feedback systems is overcome by modeling the nonaffine functions appropriately. With the help of neural network approximators, an adaptive neural controller is developed by combining the dynamic surface control (DSC) and minimal learning parameter (MLP) techniques. The key features of our approach are that, first, the restrictive assumptions on the partial derivative of nonaffine functions are removed, second, the DSC technique is used to avoid "the explosion of complexity" in the backstepping design, and the number of adaptive parameters is reduced significantly using the MLP technique, third, smooth robust compensators are employed to circumvent the influences of approximation errors and disturbances. Furthermore, it is proved that all the signals in the closed-loop system are semiglobal uniformly ultimately bounded. Finally, the simulation results are provided to demonstrate the effectiveness of the designed method. PMID- 26277011 TI - Extracting Fundamental Periods to Segment Biomedical Signals. AB - We address the problem of segmenting nearly periodic time series into period-like segments. We introduce a definition of nearly periodic time series via triplets < basic shape, shape transformation, time scaling > that covers a wide range of time series. To split the time series into periods, we select a pair of principal components of the Hankel matrix. We then cut the trajectory of the selected principal components by its symmetry axis and, thus, obtaining half-periods that are merged into segments. We describe a method of automatic selection of periodic pairs of principal components, corresponding to the fundamental periodicity. We demonstrate the application of the proposed method to the problem of period extraction for accelerometric time series of human gait. We see the automatic segmentation into periods as a problem of major importance for human activity recognition problem, since it allows to obtain interpretable segments: each extracted period can be seen as an ultimate entity of gait. The method we propose is more general compared to the application specific methods and can be used for any nearly periodical time series. We compare its performance to classical mathematical methods of period extraction and find that it is not only comparable to the alternatives, but in some cases performs better. PMID- 26277012 TI - Characterization Methods for the Detection of Multiple Voice Disorders: Neurological, Functional, and Laryngeal Diseases. AB - This paper evaluates the accuracy of different characterization methods for the automatic detection of multiple speech disorders. The speech impairments considered include dysphonia in people with Parkinson's disease (PD), dysphonia diagnosed in patients with different laryngeal pathologies (LP), and hypernasality in children with cleft lip and palate (CLP). Four different methods are applied to analyze the voice signals including noise content measures, spectral-cepstral modeling, nonlinear features, and measurements to quantify the stability of the fundamental frequency. These measures are tested in six databases: three with recordings of PD patients, two with patients with LP, and one with children with CLP. The abnormal vibration of the vocal folds observed in PD patients and in people with LP is modeled using the stability measures with accuracies ranging from 81% to 99% depending on the pathology. The spectral cepstral features are used in this paper to model the voice spectrum with special emphasis around the first two formants. These measures exhibit accuracies ranging from 95% to 99% in the automatic detection of hypernasal voices, which confirms the presence of changes in the speech spectrum due to hypernasality. Noise measures suitably discriminate between dysphonic and healthy voices in both databases with speakers suffering from LP. The results obtained in this study suggest that it is not suitable to use every kind of features to model all of the voice pathologies; conversely, it is necessary to study the physiology of each impairment to choose the most appropriate set of features. PMID- 26277013 TI - Multi-Objective Model Selection via Racing. AB - Model selection is a core aspect in machine learning and is, occasionally, multi objective in nature. For instance, hyper-parameter selection in a multi-task learning context is of multi-objective nature, since all the tasks' objectives must be optimized simultaneously. In this paper, a novel multi-objective racing algorithm (RA), namely S-Race, is put forward. Given an ensemble of models, our task is to reliably identify Pareto optimal models evaluated against multiple objectives, while minimizing the total computational cost. As a RA, S-Race attempts to eliminate non-promising models with confidence as early as possible, so as to concentrate computational resources on promising ones. Simultaneously, it addresses the problem of multi-objective model selection (MOMS) in the sense of Pareto optimality. In S-Race, the nonparametric sign test is utilized for pair wise dominance relationship identification. Moreover, a discrete Holm's step-down procedure is adopted to control the family-wise error rate of the set of hypotheses made simultaneously. The significance level assigned to each family is adjusted adaptively during the race. In order to illustrate its merits, S-Race is applied on three MOMS problems: 1) selecting support vector machines for classification; 2) tuning the parameters of artificial bee colony algorithms for numerical optimization; and 3) constructing optimal hybrid recommendation systems for movie recommendation. The experimental results confirm that S-Race is an efficient and effective MOMS algorithm compared to a brute-force approach. PMID- 26277014 TI - Low-Rank Preserving Projections. AB - As one of the most popular dimensionality reduction techniques, locality preserving projections (LPP) has been widely used in computer vision and pattern recognition. However, in practical applications, data is always corrupted by noises. For the corrupted data, samples from the same class may not be distributed in the nearest area, thus LPP may lose its effectiveness. In this paper, it is assumed that data is grossly corrupted and the noise matrix is sparse. Based on these assumptions, we propose a novel dimensionality reduction method, named low-rank preserving projections (LRPP) for image classification. LRPP learns a low-rank weight matrix by projecting the data on a low-dimensional subspace. We use the L21 norm as a sparse constraint on the noise matrix and the nuclear norm as a low-rank constraint on the weight matrix. LRPP keeps the global structure of the data during the dimensionality reduction procedure and the learned low rank weight matrix can reduce the disturbance of noises in the data. LRPP can learn a robust subspace from the corrupted data. To verify the performance of LRPP in image dimensionality reduction and classification, we compare LRPP with the state-of-the-art dimensionality reduction methods. The experimental results show the effectiveness and the feasibility of the proposed method with encouraging results. PMID- 26277015 TI - A Separated Approach to Control of Markov Jump Nonlinear Systems With General Transition Probabilities. AB - This paper is devoted to the control of Markov jump nonlinear systems with general transition probabilities (TPs) allowed to be known, uncertain, and unknown. With the help of the S-procedure to dispose the system nonlinearities and the TP property to eliminate the coupling between unknown TP and Lyapunov variable, an extended bounded real lemma for the considered system to be stochastically stable with the prescribed Hinfinity performance is established in the framework of linear matrix inequalities. To handle the nonlinearity incurred by uncertain TP for controller synthesis, a separated method is proposed to decouple the interconnection between Lyapunov variables and controller gains. A numerical example is given to show the effectiveness of the proposed method. PMID- 26277016 TI - [Use of 3D-rotational angiography in the diagnosis of the anomalous origin of the left coronary artery in the pulmonary artery]. PMID- 26277017 TI - [Different glycogen storage diseases presenting as abdominal distention and growth and weight retardation]. PMID- 26277018 TI - The attentional blink is related to phonemic decoding, but not sight-word recognition, in typically reading adults. AB - This research investigated the relationship between the attentional blink (AB) and reading in typical adults. The AB is a deficit in the processing of the second of two rapidly presented targets when it occurs in close temporal proximity to the first target. Specifically, this experiment examined whether the AB was related to both phonological and sight-word reading abilities, and whether the relationship was mediated by accuracy on a single-target rapid serial visual processing task (single-target accuracy). Undergraduate university students completed a battery of tests measuring reading ability, non-verbal intelligence, and rapid automatised naming, in addition to rapid serial visual presentation tasks in which they were required to identify either two (AB task) or one (single target task) target/s (outlined shapes: circle, square, diamond, cross, and triangle) in a stream of random-dot distractors. The duration of the AB was related to phonological reading (n=41, beta=-0.43): participants who exhibited longer ABs had poorer phonemic decoding skills. The AB was not related to sight word reading. Single-target accuracy did not mediate the relationship between the AB and reading, but was significantly related to AB depth (non-linear fit, R(2)=.50): depth reflects the maximal cost in T2 reporting accuracy in the AB. The differential relationship between the AB and phonological versus sight-word reading implicates common resources used for phonemic decoding and target consolidation, which may be involved in cognitive control. The relationship between single-target accuracy and the AB is discussed in terms of cognitive preparation. PMID- 26277019 TI - Increased alpha band activity indexes inhibitory competition across a border during figure assignment. AB - Figure-ground assignment is thought to entail inhibitory competition between potential objects on opposite sides of a shared border; the winner is perceived as the figure, and the loser as the shapeless ground. Computational models and response time measures support this understanding but to date no online measure of inhibitory competition during figure-ground assignment has been reported. The current study assays electroencephalogram (EEG) alpha power as a measure of inhibitory competition during figure-ground assignment. Activity in the EEG alpha band has been linked to functional inhibition in the brain, and it has been proposed that increased alpha power reflects increased inhibition. In 2 experiments participants viewed silhouettes designed so that the insides would be perceived as figures. Real-world silhouettes depicted namable objects. Novel silhouettes depicted novel objects on the insides of their borders, but varied in the amount of hypothesized cross-border competition for figural status: In "Low Competition" silhouettes, the borders suggested novel objects on the outside as well as on the inside. In "High-Competition" silhouettes the borders suggested portions of real-world objects on the outside; these compete with the figural properties favoring the inside as figure. Participants accurately categorized both types of novel silhouettes as "novel" objects and were unaware of the real world objects suggested on the outside of the High-Competition silhouettes. In both experiments, we observed more alpha power while participants viewed High- rather than Low-Competition novel silhouettes. These are the first results to show via an online index of neural activity that figure assignment entails inhibitory competition. PMID- 26277020 TI - Determining color difference thresholds in denture base acrylic resin. AB - STATEMENT OF PROBLEM: In restorative prostheses, color is important, but the choice of color difference formula used to quantify color change in acrylic resins is not straightforward. PURPOSE: The purpose of this in vitro study was to choose a color difference formula that best represented differences between the calculated color and the observed imperceptible to unacceptable color and to determine the corresponding perceptibility and acceptability threshold of color stability for denture base acrylic resins. MATERIAL AND METHODS: A total of 291 acrylic resin denture base plates were fabricated and subjected to radiation tests from zero to 42 hours in accordance with ISO 7491:2000. Color was measured with a portable spectrophotometer, and color differences were calculated with 3 International Commission on Illumination (CIE) formulas: CIELab, CMC(1:1), and CIEDE2000. Thirty-four observers with no deficiencies in color perception participated in psychophysical perceptibility and acceptability assessments under controlled conditions in vitro. These 2 types of assessments were regressed to each observer by each formula to generate receiver operator characteristic (ROC) curves. Areas under the curves (AUCs) were then calculated and analyzed to exclude observers with poor color discrimination. AUCs were subjected to 1-way ANOVA (alpha=.05) to deter the statistical significance of discriminability among the 3 formulas in terms of perceptibility and acceptability judgments. Student Newman-Keuls tests (alpha=.05) were used for post hoc comparison. RESULTS: CMC(1:1) and CIEDE2000 formulas performed better for imperceptible to unacceptable color differences, with corresponding CMC(1:1) and CIEDE2000 values for perceptibility of 2.52 and 1.72, respectively, and acceptability thresholds of 6.21 and 4.08, respectively. CONCLUSIONS: Formulas CMC(1:1) and CIEDE2000 possess higher discriminability than that of CIELab in the assessment of perceptible color difference threshold of denture base acrylic resin. A statistically significant difference exists between perceptibility and acceptability thresholds for denture base acrylic resin. PMID- 26277023 TI - Gradient-based enhancement of tubular structures in medical images. AB - Vesselness filters aim at enhancing tubular structures in medical images. The most popular vesselness filters are based on eigenanalyses of the Hessian matrix computed at different scales. However, Hessian-based methods have well-known limitations, most of them related to the use of second order derivatives. In this paper, we propose an alternative strategy in which ring-like patterns are sought in the local orientation distribution of the gradient. The method takes advantage of symmetry properties of ring-like patterns in the spherical harmonics domain. For bright vessels, gradients not pointing towards the center are filtered out from every local neighborhood in a first step. The opposite criterion is used for dark vessels. Afterwards, structuredness, evenness and uniformness measurements are computed from the power spectrum in spherical harmonics of both the original and the half-zeroed orientation distribution of the gradient. Finally, the features are combined into a single vesselness measurement. Alternatively, a structure tensor that is suitable for vesselness can be estimated before the analysis in spherical harmonics. The two proposed methods are called Ring Pattern Detector (RPD) and Filtered Structure Tensor (FST) respectively. Experimental results with computed tomography angiography data show that the proposed filters perform better compared to the state-of-the-art. PMID- 26277021 TI - Synergistic Effect of Simvastatin Plus Radiation in Gastric Cancer and Colorectal Cancer: Implications of BIRC5 and Connective Tissue Growth Factor. AB - PURPOSE: We investigated the synergistic effect of simvastatin, a 3-hydroxy-3 methylglutaryl coenzyme A reductase inhibitor plus radiation therapy, on the proliferation and survival of gastric cancer (GC) and colorectal cancer (CRC) cells. We also studied several genes involved in the simvastatin/radiation induced effects. METHODS AND MATERIALS: Gastric cancer (AGS, SNU601, MKN1, and MKN28) and CRC (CoLo320, SW48, HT29, and HCT8) cell lines were treated with 0.2 MUM simvastatin alone, or in combination with 0 to 4 Gy of radiation, and subjected to clonogenic survival and proliferation assays in vitro. To assess the molecular mechanism of the combination treatment, we performed microarray analysis, immunoblot assays, small interfering RNA knockdown experiments, and plasmid rescue assays. The antitumoral effects of simvastatin and radiation were evaluated in vivo using xenograft models. RESULTS: The combination therapy of simvastatin plus radiation inhibited basal clonogenic survival and proliferation of GC and CRC cells in vitro. Simvastatin suppressed the expression of BIRC5 and CTGF genes in these cancer cells. In vivo, the combined treatment with simvastatin and radiation significantly reduced the growth of xenograft tumors compared with treatment with radiation alone. CONCLUSION: We suggest that simvastatin has a synergistic effect with radiation on GC and CRC through the induction of apoptosis, which may be mediated by a simultaneous inhibition of BIRC5 and CTGF expression. A clinical trial of simvastatin in combination with radiation in patients with GC or CRC is warranted. PMID- 26277022 TI - Abdominal multi-organ segmentation from CT images using conditional shape location and unsupervised intensity priors. AB - This paper addresses the automated segmentation of multiple organs in upper abdominal computed tomography (CT) data. The aim of our study is to develop methods to effectively construct the conditional priors and use their prediction power for more accurate segmentation as well as easy adaptation to various imaging conditions in CT images, as observed in clinical practice. We propose a general framework of multi-organ segmentation which effectively incorporates interrelations among multiple organs and easily adapts to various imaging conditions without the need for supervised intensity information. The features of the framework are as follows: (1) A method for modeling conditional shape and location (shape-location) priors, which we call prediction-based priors, is developed to derive accurate priors specific to each subject, which enables the estimation of intensity priors without the need for supervised intensity information. (2) Organ correlation graph is introduced, which defines how the conditional priors are constructed and segmentation processes of multiple organs are executed. In our framework, predictor organs, whose segmentation is sufficiently accurate by using conventional single-organ segmentation methods, are pre-segmented, and the remaining organs are hierarchically segmented using conditional shape-location priors. The proposed framework was evaluated through the segmentation of eight abdominal organs (liver, spleen, left and right kidneys, pancreas, gallbladder, aorta, and inferior vena cava) from 134 CT data from 86 patients obtained under six imaging conditions at two hospitals. The experimental results show the effectiveness of the proposed prediction-based priors and the applicability to various imaging conditions without the need for supervised intensity information. Average Dice coefficients for the liver, spleen, and kidneys were more than 92%, and were around 73% and 67% for the pancreas and gallbladder, respectively. PMID- 26277024 TI - [Application of an uncertainty model for fibromyalgia]. AB - OBJECTIVES: Finding out women's experiences diagnosed with fibromyalgia applying the Theory of Uncertainty proposed by M. Mishel. DESIGN: A qualitative study was conducted, using a phenomenological approach. LOCATION: An Association of patients in the province of Alicante during the months of June 2012 to November 2013. PARTICIPANTS: A total of 14 women diagnosed with fibromyalgia participated in the study as volunteers, aged between 45 and 65 years. METHOD: Information generated through structured interviews with recording and transcription, prior confidentiality pledge and informed consent. Analysis content by extracting different categories according to the theory proposed. RESULTS: The study patients perceive a high level of uncertainty related to the difficulty to deal with symptoms, uncertainty about diagnosis and treatment complexity. Moreover, the ability of coping with the disease it is influenced by social support, relationships with health professionals and help and information attending to patient associations. CONCLUSIONS: The health professional must provide clear information on the pathology to the fibromyalgia suffers, the larger lever of knowledge of the patients about their disease and the better the quality of the information provided, it is reported to be the less anxiety and uncertainty in the experience of the disease. Likewise patient associations should have health professionals in order to avoid bias in the information and advice with scientific evidence. PMID- 26277025 TI - Multifocal TMS for temporo-spatial description of cortico-cortical connectivity patterns. PMID- 26277026 TI - Acetone-activated polyimide electrospun nanofiber membrane for thin-film microextraction and thermal desorption-gas chromatography-mass spectrometric analysis of phenols in environmental water. AB - In this work, a polyimide nanofiber membrane was electrospun and applied as sorbent for thin film microextraction (TFME). After TFME of phenols in water samples, direct thermal desorption of the sorbent at 300 degrees C followed by gas chromatography-mass spectrometric (TD-GC-MS) analysis was carried out. The extraction efficiency of TFME was enhanced by 6-12 times for phenols after activation with acetone. The positive effect of acetone activation was correlated to the increased hydrophilicity of the membrane. Extraction parameters, including mass of nanofiber membrane, pH value, NaCl concentration and extraction time, were optimized. Under optimal conditions, the LODs and LOQs for analysis of phenols in spiked purified water were 0.0006-0.008 and 0.002-0.025MUgL(-1), respectively. The linearity range was more than two orders of magnitude (R>0.99). The RSDs of intra-batch and inter-batch were 4.3-7.4% and 2.7-10.6% (n=3). Finally the method was applied to real samples, including tap water, sea water, and waste water. These results indicate that the polyimide nanofiber membrane is a promising candidate as TFME sorbent for determination of polar analytes in water samples coupled with TD-GC-MS. PMID- 26277027 TI - Development of an accurate and high-throughput methodology for structural comprehension of chlorophylls derivatives. (II) Dephytylated derivatives. AB - Dephytylated chlorophylls (chlorophyllides and pheophorbides) are the starting point of the chlorophyll catabolism in green tissues, components of the chlorophyll pattern in storage/processed food vegetables, as well as the favoured structural arrangement for chlorophyll absorption. In addition, dephytylated native chlorophylls are prone to several modifications of their structure yielding pyro-, 13(2)-hydroxy- and 15(1)-hydroxy-lactone derivatives. Despite of these outstanding remarks only few of them have been analysed by MS(n). Besides new protocols for obtaining standards, we have developed a new high throughput methodology able to determine the fragmentation pathway of 16 dephytylated chlorophyll derivatives, elucidating the structures of the new product ions and new mechanisms of fragmentation. The new methodology combines, by first time, high resolution time-of-flight mass spectrometry and powerful post-processing software. Native chlorophyllides and pheophorbides mainly exhibit product ions that involve the fragmentation of D ring, as well as additional exclusive product ions. The introduction of an oxygenated function at E ring enhances the progress of fragmentation reactions through the beta-keto ester group, developing also exclusive product ions for 13(2)-hydroxy derivatives and for 15(1)-hydroxy lactone ones. Consequently, while MS(2)-based reactions of phytylated chlorophyll derivatives point to fragmentations at the phytyl and propionic chains, dephytylated chlorophyll derivatives behave different as the absence of phytyl makes beta-keto ester group and E ring more prone to fragmentation. Proposals of the key reaction mechanisms underlying the origin of new product ions have been made. PMID- 26277028 TI - Insights into chromatographic separation using core-shell metal-organic frameworks: Size exclusion and polarity effects. AB - Porous metal-organic frameworks (MOFs) [Cu3(BTC)2(H2O)3]n (also known as HKUST-1; BTC, benzene-1,3,5-tricarboxylic acid) were synthesized as homogeneous shell onto carboxyl functionalized magnetic microparticles through a liquid phase epitaxy (LPE) process. The as-synthesized core-shell HKUST-1 magnetic microparticles composites were characterized by XRD and SEM, and used as stationary phase in high performance liquid chromatography (HPLC). The effects of the unique properties of MOFs onto the chromatographic performance are demonstrated by the experiments. First, remarkable separation of pyridine and bipyridine is achieved, although both molecules show a strong interaction between the Cu-ions in HKUST-1 and the nitrogen atoms in their heterocyles. The difference can be explained due to size exclusion of bipyridine from the well defined pore structure of crystalline HKUST-1. Second, the enormous variety of possible interactions of sample molecules with the metal ions and linkers within MOFs allows for specifically tailored solid phases for challenging separation tasks. For example, baseline separation of three chloroaniline (CLA) isomers tested can be achieved without the need for gradient elution modes. Along with the experimental HPLC runs, in-depth modelling with a recently developed chromatography modelling software (ChromX) was applied and proofs the software to be a powerful tool for exploring the separation potential of thin MOF films. The pore diffusivity of pyridine and CLA isomers within HKUST-1 are found to be around 2.3*10(-15)m(2)s( 1). While the affinity of HKUST-1 to the tested molecules strongly differs, the maximum capacities are in the same range, with 0.37molL(-1) for pyridine and 0.23molL(-1) for CLA isomers, corresponding to 4.0 and 2.5 molecules per MOF unit cell, respectively. PMID- 26277029 TI - Determination of adsorption isotherm parameters for minor whey proteins by gradient elution preparative liquid chromatography. AB - Ion-Exchange Chromatography (IEC) techniques have been extensively investigated in protein purification processes, due to the more selective and milder separation steps. To date, existing studies of minor whey proteins fractionation in IEC have primarily been conducted as batch uptake studies, which require more experimental search space, time and materials. In this work, the selected resin's (SP Sepharose FF) equilibrium and dynamic binding capacity were first investigated. Next, adsorption of the pure binary mixture of lactoperoxidase and lactoferrin was studied to calibrate steric mass action (SMA) model using a simplified approach with data from single column experiments. The calibrated model was then verified by performing factorial-design based experiments for various process operating conditions assessing process performance on a larger bed height column. The model predicted results demonstrated a realistic agreement with the experiments providing reproducible column elution profile and reduced experimental work. Finally, whey protein isolate was used to evaluate model parameters in real conditions. Results obtained herein are suitable for future large scale applications. PMID- 26277030 TI - Study of complex matrix effect on solid phase microextraction for biological sample analysis. AB - Solid phase microextraction (SPME) has become a useful tool for in vivo monitoring the behavior of environmental organic pollutants in biological species due to its simplicity, relatively non-invasive, and cost-effective manner. However, the complex matrices in biological samples could significantly influence the extraction kinetic, and bias the quantification result. In this study, we investigated the effect of complex matrix on the extraction kinetic of SPME for biological sample analysis. Two sample matrices, phosphate-buffered saline (PBS) with bovine serum albumin (BSA) and agarose gel with BSA were used to simulate the biological fluid and tissue. Results showed that the addition of BSA significantly enhanced the mass transfer of organic compounds onto SPME fiber in both PBS buffer and gel sample. Enhancement factors ranging from 1.3 to 27, and 2.0 to 80 were found for all selected polyaromatic hydrocarbons (PAHs) in PBS buffer and agarose gel with BSA concentration of 0.1-5%, respectively. Then, an improved theoretical model was applied to quantify the observed enhancement effect, and the result showed that the predicted sampling time constant agreed well with the experimental one in complex matrix. Furthermore, a simplified equation was proposed for the real biological sample analysis. PMID- 26277031 TI - Comparison of survival outcomes among standard radiotherapy regimens in limited stage small cell lung cancer patients receiving concurrent chemoradiation. AB - OBJECTIVES: The optimal radiotherapy dose in concurrent chemoradiation (CRT) for limited-stage small cell lung cancer (SCLC) is controversial. We compared the effectiveness of several high-dose chemoradiation regimens using a large national dataset. MATERIALS AND METHODS: Patients with non-metastatic SCLC treated with concurrent CRT were identified in the National Cancer Database base. Overall survival (OS) of patients receiving dose-fractionation regimens, matching those in the ongoing CALGB 30610 trial [45 Gy in 30 fractions (Fx) (45 Gy/30Fx), 70 Gy in 35 fractions (70 Gy/35Fx), and 61.2 Gy in 34 fractions (61.2 Gy/34Fx)], were compared using Kaplan-Meier analysis and multivariable Cox proportional hazards modeling. RESULTS: We included 1228 patients treated between 1998 and 2006 with CRT. Mean age was 62 years and 50% of patients were women. Radiotherapy dose fractionation was 45 Gy/30Fx in 707 (57.6%), 70 Gy/35Fx in 53 (4.3%), and 61.2 Gy/34Fx in 468 (38.1%). Overall survival was similar among patients treated with 45 Gy/30Fx, 70 Gy/35Fx, and 61.2 Gy/34Fx, with median survival times of 21.5, 21.5, and 20.2 months, respectively (p=0.438). Older age, male sex, larger tumor size, and more advanced stage were associated with inferior OS on Kaplan-Meier (all p<0.001). Cox proportional hazards modeling adjusting for these factors demonstrated similar OS among patients receiving these three dose-fractionation regimens (p=0.815). CONCLUSIONS: We observed equivalent OS among patients with limited-stage SCLC being treated with three dose-fractionation regimens of concurrent CRT. This supports the use of any one of these regimens while awaiting the results of ongoing randomized trials. PMID- 26277032 TI - Biological impact of cigarette smoke compared to an aerosol produced from a prototypic modified risk tobacco product on normal human bronchial epithelial cells. AB - Cigarette smoking causes serious and fatal diseases. The best way for smokers to avoid health risks is to quit smoking. Using modified risk tobacco products (MRTPs) may be an alternative to reduce the harm caused for those who are unwilling to quit smoking, but little is known about the toxic effects of MRTPs, nor were the molecular mechanisms of toxicity investigated in detail. The toxicity of an MRTP and the potential molecular mechanisms involved were investigated in high-content screening tests and whole genome transcriptomics analyses using human bronchial epithelial cells. The prototypic (p)MRTP that was tested had less impact than reference cigarette 3R4F on the cellular oxidative stress response and cell death pathways. Higher pMRTP aerosol extract concentrations had impact on pathways associated with the detoxification of xenobiotics and the reduction of oxidative damage. A pMRTP aerosol concentration up to 18 times higher than the 3R4F caused similar perturbation effects in biological networks and led to the perturbation of networks related to cell stress, and proliferation biology. These results may further facilitate the development of a systems toxicology-based impact assessment for use in future risk assessments in line with the 21st century toxicology paradigm, as shown here for an MRTP. PMID- 26277034 TI - Mesocorticolimbic dopamine functioning in primary psychopathy: A source of within group heterogeneity. AB - Despite similar emotional deficiencies, primary psychopathic individuals can be situated on a continuum that spans from controlled to disinhibited. The constructs on which primary psychopaths are found to diverge, such as self control, cognitive flexibility, and executive functioning, are crucially regulated by dopamine (DA). As such, the goal of this review is to examine which specific alterations in the meso-cortico-limbic DA system and corresponding genes (e.g., TH, DAT, COMT, DRD2, DRD4) might bias development towards a more controlled or disinhibited expression of primary psychopathy. Based on empirical data, it is argued that primary psychopathy is generally related to a higher tonic and population activity of striatal DA neurons and lower levels of D2-type DA receptors in meso-cortico-limbic projections, which may boost motivational drive towards incentive-laden goals, dampen punishment sensitivity, and increase future reward-expectancy. However, increasingly higher levels of DA activity in the striatum (moderate versus pathological elevations), lower levels of DA functionality in the prefrontal cortex, and higher D1-to-D2-type receptor ratios in meso-cortico-limbic projections may lead to increasingly disinhibited and impetuous phenotypes of primary psychopathy. Finally, in order to provide a more coherent view on etiological mechanisms, we discuss interactions between DA and serotonin that are relevant for primary psychopathy. PMID- 26277033 TI - Inflammatory markers and chronic exposure to fluoxetine, divalproex, and placebo in intermittent explosive disorder. AB - Intermittent Explosive Disorder (IED) is a disorder of impulsive aggression affecting 4-7% of the U.S. population during some period of life. In addition to other biological correlates, elevations of plasma inflammatory markers have been reported in IED, compared with control, subjects. In this study we sought to explore if treatment exposure to anti-aggressive agents, compared with placebo, would be associated with a reduction in circulating levels of inflammatory markers. Thirty IED subjects, from a 12-week, double-blind, randomized, placebo controlled trial of fluoxetine and divalproex, in which both pre- and post treatment levels of C-Reactive Protein (CRP), interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-alpha were obtained. Efficacy measures included the Overt Aggression Scale-Modified (OAS-M) score for Aggression and for Irritability, rate of Clinical Global Impression of Improvement (CGI-I), and rate of IED Remitters at study completion. As compared to placebo, neither fluoxetine nor divalproex reduced any of the measures of aggression. In addition, levels of CRP and pro- and anti-inflammatory cytokines showed no changes from pre- to post-treatment for any treatment condition. Correlations between pre- and post- treatment plasma CRP/cytokines were substantial (mean r=0.71, r(2)=0.50, p<0.001). Overall, circulating markers of inflammation markers were unaffected by treatment with fluoxetine or divalproex, consistent with the absence of change in measures of impulsive aggression. PMID- 26277035 TI - BDNF concentration and impulsiveness level in post-traumatic stress disorder. AB - Among the symptoms of post-traumatic stress disorder (PTSD), impulsiveness has been observed in patients with high levels of hyperarousal. Recent literature reveals the importance of investigating the role of neurotrophins, such as brain derived neurotrophic factor (BDNF), in several psychiatric disorders. Specifically, contrasting findings have been reported on the levels of serum BDNF in subjects with PTSD. The aim of the present study was to investigate the correlation between BDNF serum levels and impulsiveness in PTSD. To this end, we measured BDNF serum levels in 23 PTSD patients and a control group of 19 trauma exposed non-PTSD subjects. Results indicate a positive correlation in the PTSD group; that is, the higher the BDNF levels the higher the impulsiveness score, as measured by the Barratt Impulsiveness Scale (BIS-11), suggesting that impulsiveness could be associated with greater BDNF production. Alternatively, it is also possible that high impulsiveness acts as a psychological mechanism that counteracts the negative effects exerted by the traumatic experience and the associated obsessive thoughts. The present paper discusses both hypotheses. PMID- 26277036 TI - Para-aminosalicylic acid: the return of an old friend. AB - Para-aminosalicylic acid (PAS) is one of the last remaining drugs available to treat extensively drug-resistant (XDR) tuberculosis. Good outcomes (81% 5 year survival) were documented when PAS was first used with streptomycin, yet results of PAS with remaining potentially effective drugs for the treatment of XDR tuberculosis are poor (mortality 30-90%). In this Review, we assess published work regarding recommendations for PAS dosing in relation to efficacy and tolerance. PAS 20 g daily acoompanied only by streptomycin is better in prevention of streptomycin resistance than PAS 10 g or 5 g daily. When accompanied by isonazid, a more potent drug than streptomycin, treatment success with PAS 20 g daily is similar to that of PAS 10 g daily. In contemporary, relatively weak XDR tuberculosis regimens, the recommended doseage of PAS 8-12 g in two to three doses daily is probably insufficient. Furthermore, once daily PAS could be considered, because substantial research suggests no worse intolerance than with multiple daily PAS doses. In most countries, PAS is now available in a granular, slow-release formulation that seems well tolerated, but efficacy has never been formally assessed. Once daily dosing with granular PAS might achieve high peak concentrations and a long interval above minimum inhibitory concentration, with the advantage of improved supervision of drug intake. PMID- 26277037 TI - Clinical value of whole-genome sequencing of Mycobacterium tuberculosis. AB - Whole-genome sequencing (WGS) is now common as a result of new technologies that can rapidly sequence a complete bacterial genome for US$500 or less. Many studies have addressed questions about tuberculosis with WGS, and knowing the sequence of the entire genome, rather than only a few fragments, has greatly increased the precision of molecular epidemiology and contact tracing. Additionally, topics such as the mutation rate, drug resistance, the target of new drugs, and the phylogeny and evolution of the Mycobacterium tuberculosis complex bacteria have been elucidated by WGS. Nonetheless, WGS has not explained differences in transmissibility between strains, or why some strains are more virulent than others or more prone to development of multidrug resistance. With advances in technology, WGS of clinical specimens could become routine in high-income countries; however, its relevance will probably depend on easy to use software to efficiently process the sequences produced and accessible genomic databases that can be mined in future studies. PMID- 26277038 TI - Characterization of the SIRT family of NAD+-dependent protein deacetylases in the context of a mammalian model of hibernation, the thirteen-lined ground squirrel. AB - Hibernating mammals employ strong metabolic rate depression to survive the winter, thereby avoiding the high energy costs of maintaining a euthermic lifestyle in the face of low seasonal temperatures and limited food resources. Characteristics of this natural torpor include a significant reduction in body temperature, a shift to a lipid-based metabolism, global suppression of ATP expensive activities, and the upregulation of selected genes that mediate biochemical reorganization and cytoprotection. Sirtuin (SIRT) proteins, an evolutionarily conserved family of NAD(+)-dependent protein deacetylases, have been shown to play important roles in the post-translational regulation of many metabolic and cytoprotective processes, suggesting a potential function for these enzymes in the control of hibernation. To assess this possibility, protein levels of the seven mammalian SIRTs (SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6 and SIRT7), total SIRT activity, and the acetylation status of two downstream SIRT targets (SOD2K68 and NF-kappaB p65K310) were measured in skeletal muscle, liver, brown adipose and white adipose tissues of the hibernating thirteen-lined ground squirrel (Ictidomys tridecemlineatus) over the course of the torpor-arousal cycle. The analysis revealed tissue-specific responses of different SIRTs at various points throughout hibernation, including a potentially interesting correlation between increased levels of SIRT3 protein, heightened total SIRT activity, and decreased acetylation of SIRT3 downstream target SOD2K68 in skeletal muscle during late torpor. These results provide evidence to suggest a possible role for the SIRT family of protein deacetylases in the regulation of the metabolic and cellular protective pathways that mediate the process of mammalian hibernation. PMID- 26277039 TI - Successful ram semen cryopreservation with lyophilized egg yolk-based extender. AB - The aim of this study was to evaluate the effects of lyophilized egg yolk extender on ram semen cryopreservation. Ejaculates with a thick consistency, rapid wave motion (3-5 on a 0-5 scale) and >75% initial motility were pooled. Sperm were diluted to final concentration of 1/5 (semen/extender) in lyophilized egg yolk or fresh egg yolk extenders using two-step dilution method. The equilibrated semen was frozen in 0.25 mL straws. Semen samples were assessed for sperm motility, plasma membrane functional integrity using hypoosmotic swelling test (HOST), damaged acrosome using FITC-Pisum sativum agglutinin (PSA-FITC) and DNA integrity using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) at three time points: after dilution with extender A, equilibration and post-thaw. The results showed that freezing and thawing procedures (dilution, equilibration and thawing) had negative effects on motility (P<0.001), plasma membrane integrity (P<0.001), acrosome integrity (P<0.001) and DNA integrity (P<0.001). In the study, there were no significant differences between lyophilized and fresh egg yolk extenders when comparing motility, plasma membrane integrity, acrosome integrity and DNA integrity between groups. In conclusion, lyophilized egg yolk extender provided similar cryoprotective effects with fresh egg yolk extender to cryopreserve ram semen. PMID- 26277040 TI - Update on Hidradenitis Suppurative (Part II): Treatment. AB - Although hidradenitis suppurativa is a common and serious skin condition, its treatment is not well established. It is now accepted that the moderate and severe forms of the disease are associated with marked systemic inflammation. The goal of treatment in hidradenitis suppurative is therefore to achieve systemic control of inflammation. In some cases, surgery may also be necessary to reduce the severity of the manifestations of cutaneous inflammation. Recent advances in our understanding of hidradenitis suppurativa have been accompanied by the emergence of novel approaches to its treatment, including the use of certain biologic drugs. Several clinical trials have been undertaken to test the effects of biologics (mainly adalimumab) in this setting. In this review, we analyze the different treatments available for hidradenitis suppurativa. PMID- 26277041 TI - Paroxysmal sympathetic hyperactivity in pediatric traumatic brain injury: A case series of four patients. AB - Paroxysmal sympathetic hyperactivity (PSH) is a condition in which there is extreme autonomic dysregulation leading to multiple episodes of sympathetic hyperactivity. Its occurrence after traumatic brain injury (TBI) in pediatric population is a neglected scenario. In our series, all pediatric patients with moderate and severe head injuries were studied and those patients who developed PSH were monitored for the PSH episodes. Four children out of 36 cases of pediatric severe traumatic brain injury developed features of PSH. Admission GCS of 3 children were 4/15 and 1 child was 6/15 and each of them had an ICU stay of more than 2 weeks and a poor DRS score at discharge. The presence of PSH is known to produce poorer outcome in terms of overall mortality, time needed for recovery, chances of developing infections, etc. which was also seen in these cases presented here. Though some studies have provided guidelines for the management of PSH like symptomatic management and use of drugs like clonidine, bromocriptine, benzodiazepines, and gabapentin, strict management guidelines are not established and exact incidence in pediatric population is not determined. PMID- 26277042 TI - The bilingual advantage debate: Moving toward different methods for verifying its existence. PMID- 26277043 TI - A quality initiative of postoperative radiographic imaging performed on mastectomy specimens to reduce histology cost and pathology report turnaround time. AB - Breast pathology relies on gross dissection for accurate diagnostic work, but challenges can necessitate submission of high tissue volumes resulting in excess labor, laboratory costs, and delays. To address these issues, a quality initiative was created through implementation of the Faxitron PathVision specimen radiography system as part of the breast gross dissection protocol; this report documents its impact on workflow and clinical care. Retrospective data from 459 patients who underwent simple or modified radical mastectomy at our institution between May 2012 and December 2014 were collected. Comparison was made between the mastectomy specimen control group before radiography use (233 patients, 340 breasts) and Faxitron group that underwent postoperative radiography (226 patients, 338 breasts). We observed a statistically significant decrease in mean number of blocks between control and Faxitron groups (47.0 vs 39.7 blocks; P<.0001), for calculated cost savings of US $146 per mastectomy. A statistically significant decrease in pathology report turnaround time was also observed (4.2 vs 3.8days; P=.038). Postoperative mastectomy specimen radiography has increased workflow efficiency and decreased histology costs and pathology report turnaround time. These findings may underestimate actual benefits and highlight the importance of quality improvement projects in anatomical pathology. PMID- 26277044 TI - Association between alcohol and substance use disorders and all-cause and cause specific mortality in schizophrenia, bipolar disorder, and unipolar depression: a nationwide, prospective, register-based study. AB - BACKGROUND: People with severe mental illness have both increased mortality and are more likely to have a substance use disorder. We assessed the association between mortality and lifetime substance use disorder in patients with schizophrenia, bipolar disorder, or unipolar depression. METHODS: In this prospective, register-based cohort study, we obtained data for all people with schizophrenia, bipolar disorder, or unipolar depression born in Denmark in 1955 or later from linked nationwide registers. We obtained information about treatment for substance use disorders (categorised into treatment for alcohol, cannabis, or hard drug misuse), date of death, primary cause of death, and education level. We calculated hazard ratios (HRs) for all-cause mortality and subhazard ratios (SHRs) for cause-specific mortality associated with substance use disorder of alcohol, cannabis, or hard drugs. We calculated standardised mortality ratios (SMRs) to compare the mortality in the study populations to that of the background population. FINDINGS: Our population included 41 470 people with schizophrenia, 11 739 people with bipolar disorder, and 88 270 people with depression. In schizophrenia, the SMR in those with lifetime substance use disorder was 8.46 (95% CI 8.14-8.79), compared with 3.63 (3.42-3.83) in those without. The respective SMRs in bipolar disorder were 6.47 (5.87-7.06) and 2.93 (2.56-3.29), and in depression were 6.08 (5.82-6.34) and 1.93 (1.82-2.05). In schizophrenia, all substance use disorders were significantly associated with increased risk of all-cause mortality, both individually (alcohol, HR 1.52 [95% CI 1.40-1.65], p<0.0001; cannabis, 1.24 [1.04-1.48], p=0.0174; hard drugs, 1.78 [1.56-2.04], p<0.0001) and when combined. In bipolar disorder or depression, only substance use disorders of alcohol (bipolar disorder, HR 1.52 [95% CI 1.27-1.81], p<0.0001; depression, 2.01 [1.86-2.18], p<0.0001) or hard drugs (bipolar disorder, 1.89 [1.34-2.66], p=0.0003; depression, 2.27 [1.98-2.60], p<0.0001) increased risk of all-cause mortality individually. INTERPRETATION: Mortality in people with mental illness is far higher in individuals with substance use disorders than in those without, particularly in people who misuse alcohol and hard drugs. Mortality-reducing interventions should focus on patients with a dual diagnosis and seek to prevent or treat substance use disorders. FUNDING: The Lundbeck Foundation. PMID- 26277045 TI - Drug-related mortality in psychiatric patients. PMID- 26277046 TI - Human Papillomavirus Biology, Pathogenesis, and Potential for Drug Discovery: A Literature Review for HIV Nurse Clinical Scientists. AB - Persistent oncogenic human papillomavirus (HPV) infection increases the probability that precancerous anal high-grade squamous intraepithelial lesions will progress to invasive anal cancer. Anal neoplasia associated with HPV disproportionately affects HIV-infected individuals, especially men who have sex with men. Prevention is limited to HPV vaccine recommendations, highlighting the need for new treatments. The purpose of this review is to provide HIV information to nurse clinical scientists about HPV-related cancer to highlight the connection between: (a) HPV biology and pathogenesis and (b) the development of drugs and novel therapeutic methods using high-throughput screening. PubMed and CINAHL were used to search the literature to determine HPV-related epidemiology, biology, and use of high-throughput screening for drug discovery. Several events in the HPV life cycle have the potential to be developed into biologic targets for drug discovery using the high-throughput screening technique, which has been successfully used to identify compounds to inhibit HPV infections. PMID- 26277047 TI - Real-time characterization of the uterine blood flow in mares before and after artificial insemination. AB - The present experiment was divided into two studies to investigate the effect of age and endometrial degeneration on uterine blood flow of mares throughout the immediate post-breeding period. In study 1, uterine blood flow was characterized in mares (n = 7 mares/group) with minimal, moderate or severe endometrial degenerative changes (GI, GII and GIII, respectively). In study 2, the effect of age was investigated using young (<= 6 years) and old (>= 15 years) mares (n = 7 mares/group). Uterine vascular perfusion and mesometrial pulsatility index (PI) were evaluated every hour from H0 (moment immediately before AI) to H12. In study 1, a pronounced and transitory increase on uterine vascular perfusion was detected (P < 0.001) between H1 and H3 in the three endometrial groups. In addition, GIII mares had greater (P < 0.05) mesometrial PI than GI mares during the post-breeding period, denoting reduced uterine blood flow. In study 2, a transitory increase on uterine vascular perfusion was also observed in both age groups during the first hour after mating. However, mesometrial PI of young and old mares was similar (P > 0.05) and constant (P > 0.7) through the first 12h after AI. Results demonstrated, for the first time, the immediate changes on uterine vascular perfusion and mesometrial PI in response to semen infusion. Moreover, reduced blood flow of the uterus during the post-breeding period was strongly associated with endometrial degenerative changes in mares, regardless of age. PMID- 26277048 TI - Modeling the hypothalamus-pituitary-adrenal axis: A review and extension. AB - Multiple models of the hypothalamus-pituitary-adrenal (HPA) axis have been developed to characterize the oscillations seen in the hormone concentrations and to examine HPA axis dysfunction. We reviewed the existing models, then replicated and compared five of them by finding their correspondence to a dataset consisting of ACTH and cortisol concentrations of 17 healthy individuals. We found that existing models use different feedback mechanisms, vary in the level of details and complexities, and offer inconsistent conclusions. None of the models fit the validation dataset well. Therefore, we re-calibrated the best performing model using partial calibration and extended the model by adding individual fixed effects and an exogenous circadian function. Our estimated parameters reduced the mean absolute percent error significantly and offer a validated reference model that can be used in diverse applications. Our analysis suggests that the circadian and ultradian cycles are not created endogenously by the HPA axis feedbacks, which is consistent with the recent literature on the circadian clock and HPA axis. PMID- 26277049 TI - Wintertime haze deterioration in Beijing by industrial pollution deduced from trace metal fingerprints and enhanced health risk by heavy metals. AB - Airborne particulate matter (PM) was collected in Beijing between 24 February and 12 March 2014 to investigate chemical characteristics and potential industrial sources of aerosols along with health risk of haze events. Results showed secondary inorganic aerosol was the major contributor to PM2.5 during haze days. Utilizing specific elements, including Fe, La, Tl and As, as fingerprinting tracers, four emission sources, namely iron and steel manufacturing, petroleum refining, cement plant, and coal combustion were explicitly identified; their elevated contributions to PM during haze days were also estimated. The average cancer risk from exposure to inhalable PM toxic metals was 1.53 * 10(-4) on haze days, which is one order of magnitude higher than in other developed cities. These findings suggested heavy industries emit large amounts of not only primary PM but also precursor gas pollutants, leading to secondary aerosol formation and harm to human health during haze days. PMID- 26277050 TI - Effects of feeding different lipid sources on hepatic histopathology features and growth traits of broiler chickens. AB - The effects of different dietary lipid sources on growth traits and hepatic histopathology of broiler chickens were investigated. Hubbard strain one-day old chickens (n=120) were kept in pens and were fed one of the three corn-soybean meal-based diets until 49 days of age. The dietary treatments consisted of 2.5% added oil or fat from three sources as follows: SFO diet containing sunflower oil; LRD diet containing lard, and EVOO diet containing extra-virgin olive oil. Dietary oil or fat type improved significantly body weight and gain as well as feed efficiency in birds fed EVOO compared to those fed the other treatments. Based on our findings, after the whole experimental feeding period it was possible to observe relevant injuries to the liver of the chicks fed with lard, whereas the hepatic histopathological changes appeared less marked or absent in the chicks fed vegetable oils from sunflower or olive. Thus, we can conclude that dietary lipid source affected chicks performance and hepatic histopathology especially when chicks fed diet containing animal fats; whereas feeding extra virgin olive oil supported positively growth traits and did not result in hepatic histopathological effects. PMID- 26277052 TI - Clinical potential of boron neutron capture therapy for locally recurrent inoperable previously irradiated head and neck cancer. AB - This review compares the safety and efficacy of boron neutron capture therapy (BNCT) in the treatment of previously irradiated, inoperable locoregional recurrent HNC patients and compares BNCT against the standard treatment of platinum-based chemotherapy. Our analysis of published clinical trials highlights efficacy of BNCT associated with mild side effects. However, the use of BNCT should be explored in stratified randomised trials. PMID- 26277051 TI - Cyclo-Gly-Pro, a cyclic dipeptide, attenuates nociceptive behaviour and inflammatory response in mice. AB - The present study aimed to investigate the antinociceptive and anti-inflammatory effects of the cyclic dipeptide cyclo-Gly-Pro (CGP) in mice. Antinociceptive activity was assessed by employing different pain models, such as formalin test, acetic acid-induced writhing, hot plate test, and carrageenan-induced hyperalgesia, in mice. The number of c-Fos-immunoreactive cells in the periaqueductal gray (PAG) was evaluated in CGP-treated mice. Anti-inflammatory activity was evaluated using paw oedema induced by carrageenan, compound 48/80, serotonin, and prostaglandin E2 (PGE2) and analyzed by plethysmometry. Quantitation of myeloperoxidase (MPO) in the paw was carried out to analyze the presence of neutrophils in the tissue. Intraperitoneal injection of CGP produced a significant inhibition in both neurogenic and inflammatory phases of formalin induced pain. The antinociceptive effect of CGP, evaluated in the acetic acid induced writhing test, was detected for up to 6 h after treatment. Further, in the hot plate test, antinociceptive behaviour was evoked by CGP, and this response was inhibited by naloxone. Animals treated with CGP did not present changes in motor performance. In CGP-treated mice there was an increase in the number of c-Fos-positive neurons in the periaqueductal gray. In another set of experiments, CGP attenuated the hyperalgesic response induced by carrageenan. Furthermore, CGP also reduced the carrageenan-increased MPO activity in paws. In addition, CGP also reduced the paw oedema evoked by compound 48/80, serotonin, and PGE2 . Taken together, these results may support a possible therapeutic application of the cyclic dipeptide cyclo-Gly-Pro toward alleviating nociception and damage caused by inflammation conditions. PMID- 26277053 TI - Relationship between Root Apices and the Mandibular Canal: A Cone-beam Computed Tomographic Analysis in a German Population. AB - INTRODUCTION: The purpose of this study was to assess the mean distance between the mandibular canal and the apices of the adjacent teeth. METHODS: Six hundred twenty-seven full-size cone-beam computed tomographic radiographs (Planmeca Promax3D; Planmeca, Helsinki, Finland; volume 8 * 8cm, voxel size <=0.2 mm) of a German population (female = 58.2%, male = 41.8%, mean age = 51 years) were analyzed to establish the shortest distance between the mandibular canal and the root apices of the second premolar and all molars using the multiplanar reconstruction of the manufacturer's software in 3 mutually orthogonal planes. The obtained metric data were statistically analyzed using Student-Neumann-Keuls and Scheffe tests. Concerning the position of the tooth, the left or right side, and the sex of the patients, the chi-square test was used. RESULTS: A total of 821 second mandibular premolars and 597 first, 508 second, and 48 third mandibular molars were included, and the mean distances were 4.2, 4.9, 3.1, and 2.6 mm, respectively. The occurrence of a direct relationship between the root tips and the mandibular canal was found in 3.2%, 2.9%, 15.2%, and 31.3% of the teeth. Women were almost twice as often affected as men. No significant differences were found concerning the location (right/left) of the teeth (P > .05). Significantly shorter distances from the mandibular canal to the root apices were found in patients younger than 35 years compared with older patients (P < .0012). CONCLUSIONS: Direct communication between the root apices and the mandibular canal is not rare and has to be taken into consideration when performing surgical or endodontic procedures to avoid iatrogenic nerve damages. Distances depend on sex and age. PMID- 26277054 TI - [Prostatic abscess: Clinical case and a literature review]. PMID- 26277055 TI - [Arthropathy due to B19 parvovirus in adults]. PMID- 26277057 TI - [Twin brothers, same reason for consulting, different days]. PMID- 26277058 TI - [Cold agglutinin disease secondary to Epstein-Barr virus infection: A rare complication of a common disease]. PMID- 26277059 TI - When top predators become prey: Black bears alter movement behaviour in response to hunting pressure. AB - The trade-off between predator avoidance and foraging is a key decision making factor that shapes an organism's adaptive behaviour and movement patterns. Human hunters act as top predators to influence the behaviour of free-ranging mammals, including large carnivorous species such as black bears (Ursus americanus). Analysing the effects of hunting on animal behavioural patterns is essential for understanding the extent to which animals detect and respond to human-induced disturbances. To this end, we assessed whether black bear movement behaviour changed with varying risk from spatially and temporally heterogeneous human predation. Levels of risk were categorized as either low (disturbance from dog training; n=19 bears) or high (disturbance from hunting activities; n=11 bears). Road types were either paved (risk due to vehicles) or non-paved (risk due to hunters) and were used as proxies for hunting effort and amount of disturbance. We began by testing the null hypothesis that bears' distribution before the onset of human disturbance is spatially random. Next, to test temporal movement adjustment between the low and high risk levels, we measured the distance to the nearest road and the road crossing frequency using mixed effects models with risk level, time of day and sex as predictor variables. As disturbance near non-paved roads increased due to the start of the hunting activity, the mean distances of bears to non-paved roads increased while the mean distances of bears to paved roads decreased, despite the continual risk of vehicle collision. These behavioural responses were observed during day and night, with the frequency of crossing paved roads at night five times greater than in daytime during the hunting season. Our findings demonstrate that black bears are able to detect risky places and adjust their spatial movements accordingly. More specifically, bears can perceive changes in the level of risk from human hunting activities on a fine temporal scale. PMID- 26277060 TI - Do dogs (Canis lupus familiaris) prefer family? AB - Kin recognition requires the ability to discriminate between one's own genetic relatives and non-relatives. There are two mechanisms that aid in kin discrimination: phenotype matching and familiarity. Dogs may be a good model for assessing these mechanisms as dogs are a promiscuous social species with a keen sense of smell. Domestic dogs of both sexes were presented with two scents (close kin, distant-kin) and preference was assessed through three measures (latency to approach, number of visits, time spent). Experiment 1 explored the possibility of phenotype matching as subjects had no contact with sires, whose scent was presented alongside a control male's scent. Experiment 2 explored recognition of siblings raised with the subjects and then separated at seven weeks of age. Whereas female dogs in this experiment did not show a statistically significant preference, male dogs showed a preference for distant-kin when presented with sire and female sibling samples. PMID- 26277061 TI - The distribution of branch lengths in phylogenetic trees. AB - A lot of effort has been devoted to analyze the distribution of branching times observed in a phylogenetic tree. On the other hand, the distribution of branch lengths has not received similar attention. In this paper, the distribution of branch lengths is studied. It is shown that different types of branches within a tree have distinct distributions. Some equations to predict these distributions are derived with respect to diversification parameters and whether the size of the tree is known or not. A simulation study validated these predictions. The inferred distributions are used to develop graphical and statistical tools to assess the goodness-of-fit of diversification models. An application is presented on a recently published dated phylogeny of Carnivora. Some future developments are discussed. PMID- 26277062 TI - Glucose stimulates chondrocyte differentiation of vascular smooth muscle cells and calcification: A possible role for IL-1beta. AB - Vascular calcification is a hallmark of type 2 diabetes. Glucose stimulates calcification in culture of vascular smooth muscle cells (VSMCs) but the underlying mechanisms remain obscure. We observed that high glucose levels stimulated mouse and human VSMC trans-differentiation into chondrocytes, with increased levels of Sox9, type II collagen, glycosaminoglycan and Runx2 expression, and increased alkaline phosphatase activity and mineralization. These effects were associated with increased expression of IL-1beta, which stimulated alkaline phosphatase and calcification, suggesting that glucose induces chondrocyte differentiation of VSMCs, possibly through IL-1beta activation. PMID- 26277063 TI - Congenital uveal melanoma? AB - A 3-month-old infant with a white mother and Asian father presented with discoloration and prominence of the left eye since birth. Examination revealed a normal right eye. The left eye had hyperchromic heterochromia and an enlarged cornea (diameter, 13.0 mm) with intraocular pressure of 26 mm Hg. There were multiple areas of subconjunctival nodular pigmentation that extended posteriorly into the superior fornix. Fundus examination showed a large ciliochoroidal pigmented mass extending from 10:30 to 3:00 o'clock position involving the superior half of the choroid and adjacent ciliary body. The eye was enucleated, confirming the diagnosis of diffuse uveal melanoma with extraocular extension. Systemic surveillance (hepatic panel and ultrasonography of the liver) performed every 6 months for 5 years was has been negative for metastases. The tumor was investigated intensively for the panel of genes (BAP1, BRAF, NRAS12, NRAS61, GNAQ, Kit 9,11,13,17,18) implicated in pathogenesis of blue nevus, cutaneous melanoma, and mucosal melanomas with negative results. Moreover, germline BAP1 mutation could not be identified. This case possibly represents as yet unidentified uveal melanocytic proliferation rather than a true variant of uveal melanoma. PMID- 26277064 TI - Comparison of the uptake of methacrylate-based nanoparticles in static and dynamic in vitro systems as well as in vivo. AB - Polymer-based nanoparticles are promising drug delivery systems allowing the development of new drug and treatment strategies with reduced side effects. However, it remains a challenge to screen for new and effective nanoparticle based systems in vitro. Important factors influencing the behavior of nanoparticles in vivo cannot be simulated in screening assays in vitro, which still represent the main tools in academic research and pharmaceutical industry. These systems have serious drawbacks in the development of nanoparticle-based drug delivery systems, since they do not consider the highly complex processes influencing nanoparticle clearance, distribution, and uptake in vivo. In particular, the transfer of in vitro nanoparticle performance to in vivo models often fails, demonstrating the urgent need for novel in vitro tools that can imitate aspects of the in vivo situation more accurate. Dynamic cell culture, where cells are cultured and incubated in the presence of shear stress has the potential to bridge this gap by mimicking key-features of organs and vessels. Our approach implements and compares a chip-based dynamic cell culture model to the common static cell culture and mouse model to assess its capability to predict the in vivo success more accurately, by using a well-defined poly((methyl methacrylate)-co-(methacrylic acid)) and poly((methyl methacrylate)-co-(2 dimethylamino ethylmethacrylate)) based nanoparticle library. After characterization in static and dynamic in vitro cell culture we were able to show that physiological conditions such as cell-cell communication of co-cultured endothelial cells and macrophages as well as mechanotransductive signaling through shear stress significantly alter cellular nanoparticle uptake. In addition, it could be demonstrated by using dynamic cell cultures that the in vivo situation is simulated more accurately and thereby can be applied as a novel system to investigate the performance of nanoparticle systems in vivo more reliable. PMID- 26277066 TI - All [post-cardiac arrest patients] are [not] created equal. PMID- 26277067 TI - Genetic and clinical characterization of canine leishmaniasis caused by Leishmania (Leishmania) infantum in northeastern Argentina. AB - Leishmaniases comprise zoonotic diseases caused by protozoan flagellates of the Leishmania genus. They are endemic to South America, and the visceral form has been recently reported in Argentina. Dogs can play different roles in the Leishmania transmission cycles, depending mainly on the species of parasite involved. Here we focused on the clinical characterization of canine leishmaniasis (CanL) in Northeast Argentina and on the molecular typing of its etiological agent. The nested polymerase chain reaction and sequence analysis of the Leishmania cytochrome b (cyt b) gene was performed on DNA templates purified from lymph nodes, bone marrow or spleen aspirates obtained from 48 dogs previously diagnosed by the observation of Leishmania amastigotes on smears from these aspirates. Their clinical and epidemiological data were also recorded. Systemic abnormalities were observed in 46 subjects (95.8%), most frequently lymphadenopathy, and emaciation (89.6 and 75%). Furthermore, 87% also presented tegumentary abnormalities, such as alopecia (54.2%) or secondary skin lesions (47.9%), among others. Twenty three dogs were positive for cyt b amplification. The sequence analysis showed the presence of two genotypes, LiA1 and LiA2, assigned to Leishmania (Leishmania) infantum, with 99.9 and 100% homology with the reference strain MHOM/TN/80/IPT1 respectively. LiA1 was identified in 18 cases (78.3%) and LiA2 in five (21.7%). Two cyt b variants of L. (L.) infantum were incriminated as the causative agents of CanL cases from three cities: Posadas, Garupa, and Ituzaingo. All three cities are located in the northeastern area of the country, where these parasites seem to be spreading in urban areas. PMID- 26277068 TI - Estimated and reported incidence of pertussis in Estonian adults: A seroepidemiological study. AB - OBJECTIVES: Rates of pertussis immunisation among children in Estonia are high (~95%), but pertussis is still the most common vaccine preventable childhood disease. Adults are suspected to be sources of pertussis in children. We aimed to measure pertussis toxin (PT) IgG in adults to estimate pertussis infection activity and compare estimated and reported pertussis incidences. METHODS: In a cross-sectional serosurvey, consecutive leftover blood sera (n=3327) from subjects aged 20-99 years old were collected at Quattromed HTI laboratories between the 7th January and 27th February 2013. Anti-PT IgG concentration was measured by ELISA (Euroimmun, Lubeck, Germany). Estimated annual pertussis incidence was calculated for 10-year age classes using de Melker et al. (2006. J Infect. 53(2):106-13) formula. RESULTS: The mean number of samples in each 10 year age class was 466 (SD 20.5), except for 90-99 year olds which contained 65 samples. More than half of all subjects (58.1%) had anti-PT IgG <5.0IU/mL, 2.7% had 62.5 to <125IU/mL and 0.6% >=125IU/mL; no differences occurred between 10 year age classes. Estimated incidence of pertussis infection was 5.8% (95% CI 4.8 7.0) in 2012, with peaks observed in 20-29 year olds (11.0%; 95% CI 7.4-15.6) and 90-99 year olds (10.8%; 95% CI 3.0-26.2). Estimated pertussis incidence rate was 915 times higher than reported. Of 80 subjects with anti-PT IgG >=62.5IU/mL, 25 (31.3%) had complained of coughing to their GP during the previous six months. CONCLUSION: The frequency of pertussis infection was similar for all ages, suggesting similar Bordetella pertussis activity in adults and children. The wide gap between reported and estimated incidence indicates poor recognition of pertussis, likely owing to it being an asymptomatic or mild disease. PMID- 26277069 TI - Establishment of functional influenza virus-specific CD8(+) T cell memory pools after intramuscular immunization. AB - The emergence of the avian-origin influenza H7N9 virus and its pandemic potential has highlighted the ever-present need to develop vaccination approaches to induce cross-protective immunity. In this study, we examined the establishment of cross reactive CD8(+) T cell immunity in mice following immunization with live A/Puerto Rico/8/1934 (PR8; H1N1) influenza virus via two non-productive inoculation routes. We found that immunization via the intramuscular (IM) route established functional influenza-virus specific memory CD8(+) T cell pools capable of cross reactive recall responses. Epitope-specific primary, memory and recall CD8(+) T cell responses induced by the IM route, highly relevant to human influenza immunisations, were of comparable magnitude and quality to those elicited by the intraperitoneal (IP) priming, commonly used in mice. Furthermore, IM immunisation resulted in lower lung viral titres following heterologous challenge with A/Aichi/68 (X31; H3N2) compared to the IP route. Examining the ability of DCs from lymphoid organs to present viral antigen revealed that immune induction following IM immunization occurred in draining lymph nodes, while immunization via the IP route resulted in the priming of responses in distal lymphoid organs, indicative of a systemic distribution of antigen. No major differences in the pulmonary cytokine environment of immunized animals following X31 challenge were observed that could account for the improved heterologous protection induced by the IM route. However, while both routes induced similar levels of PR8-specific antibodies, higher levels of cross-reactive antibodies against X31 were induced following IM inoculation. Our data demonstrate how non-replicative routes of infection can induce efficient cross-reactive CD8(+) T cell responses and strong strain-specific antibody responses, with the additional benefit from IM priming of enhanced heterosubtypic antibody production. PMID- 26277065 TI - Stromal barriers and strategies for the delivery of nanomedicine to desmoplastic tumors. AB - Nanoparticle based delivery formulations have become a leading delivery strategy for cancer imaging and therapy. The success of nanoparticle-based therapy relies heavily on their ability to utilize the enhanced permeability and retention (EPR) effect and active targeting moieties to their advantage. However, these methods often fail to enable a uniform NP distribution across the tumor, and lead to insufficient local concentrations of drug. Oftentimes, this heterogeneous drug distribution is one of the primary reasons for suboptimal treatment efficacy in NP delivery platforms. Herein, we seek to examine the biophysical causes of heterogeneous NP distribution in stroma-rich desmoplastic tumors; namely the abnormal tumor vasculature, deregulated extracellular matrix and high interstitial hypertension associated with these tumors. It is suggested that these factors help explain the discrepancy between promising outlooks for many NP formulations in preclinical studies, but suboptimal clinical outcomes for most FDA approved nanoformulations. Furthermore, examination into the role of the physicochemical properties of NPs on successful drug delivery was conducted in this review. In light of the many formidable barriers against successful NP drug delivery, we provided possible approaches to mitigate delivery issues from the perspective of stromal remodeling and NP design. In all, this review seeks to provide guidelines for optimizing nanoparticle-based cancer drug delivery through both modified nanoparticle design and alleviation of biological barriers to successful therapy. PMID- 26277070 TI - Characterization and optimization of a novel vaccine for protection against Lyme borreliosis. AB - Lyme borreliosis (LB) is the most common vector-borne disease in the northern hemisphere and there is no vaccine available for disease prevention. The majority of LB cases in Europe are caused by four different Borrelia species expressing six different OspA serotypes, whereas in the US only one of these serotypes is present. Immunization with the outer surface protein A (OspA) can prevent infection and the C-terminal part of OspA is sufficient for protection against infection transmitted by Ixodes ticks. Here we show that the order of the stabilized monomeric OspA fragments making up the heterodimers in our LB vaccine does not influence the induced immunogenicity and protection. Using bioinformatics analysis (surface electrostatics), we have designed an improved version of an LB vaccine which has an increased immunogenicity for OspA serotype 3 and an optimized expression and purification profile. The OspA heterodimers were highly purified with low amounts of endotoxin, host cell proteins and host cell DNA. All three proteins were at least 85% triacylated which ensured high immunogenicity. The LB vaccine presented here was designed, produced and characterized to a level which warrants further development as a second generation human LB vaccine. PMID- 26277071 TI - Maternal immunization in Argentina: A storyline from the prospective of a middle income country. AB - The importance of vaccination during pregnancy lies not only in directly protecting vaccinated women, but also by indirectly protecting small infants during the first few months of life. Vaccination against the flu and whooping cough is a priority within the comprehensive care strategy for pregnant women and small infants in Argentina, in the context of transitioning from child vaccination to family vaccination. In 2011, the flu vaccine was included in the National Immunization Schedule (NIS) as mandatory and free of charge, with the aim of decreasing complications and death due to influenza in the at-risk population in Argentina. The national vaccination coverage attained in pregnant women in the past 4 years (2011-2014) has been satisfactory; 88% coverage was attained in the year this program was introduced to the schedule. In the following years, coverage was maintained at greater than 95%. In February 2012, Argentina became the first country in Latin America to have universal vaccination strategy for pregnant women against whooping cough. This recommendation was implemented throughout the country by vaccination with the diphtheria toxoid, tetanus toxoid, and acellular pertussis (Tdap) vaccine starting at 20 weeks of pregnancy, with the aim of decreasing morbimortality due to whooping cough in infants under 6 months of age. The vaccine was incorporated into the NIS in 2014. More than 1,200,000 doses were applied in this period. Both vaccines showed a suitable safety profile and no serious events were reported. Argentina is an example of a middle-income country that has been able to implement a successful strategy for primary prevention through vaccines, making it a health policy. PMID- 26277072 TI - Antibodies elicited by yeast glycoproteins recognize HIV-1 virions and potently neutralize virions with high mannose N-glycans. AB - The glycan shield on the human immunodeficiency virus 1 (HIV-1) envelope (Env) glycoprotein has drawn attention as a target for HIV-1 vaccine design given that an increasing number of potent and broadly neutralizing antibodies (bNAbs) recognize epitopes entirely or partially comprised of high mannose type N-linked glycans. In an attempt to generate immunogens that target the glycan shield of HIV-1, we previously engineered a triple mutant (TM) strain of Saccharomyces cerevisiae that results in exclusive presentation of high mannose type N-glycans, and identified five TM yeast glycoproteins that support strong binding of 2G12, a bNAb that targets a cluster of high mannose glycans on the gp120 subunit of Env. Here, we further analyzed the antigenicity and immunogenicity of these proteins in inducing anti-HIV responses. Our study demonstrated that the 2G12-reactive TM yeast glycoproteins efficiently bound to recently identified bNAbs including PGT125-130 and PGT135 that recognize high mannose glycan-dependent epitopes. Immunization of rabbits with a single TM yeast glycoprotein (Gp38 or Pst1), when conjugated to a promiscuous T-cell epitope peptide and coadministered with a Toll like receptor 2 agonist, induced glycan-specific HIV-1 Env cross-reactive antibodies. The immune sera bound to both synthetic mannose oligosaccharides and gp120 proteins from a broad range of HIV-1 strains. The purified antibodies recognized and captured virions that contain both complex- and high mannose-type of N-glycans, and potently neutralized virions from different HIV-1 clades but only when the virions were enforced to retain high mannose N-glycans. This study provides insights into the elicitation of anti-carbohydrate, HIV-1 Env-cross reactive antibodies with a heterologous glycoprotein and may have applications in the design and administration of immunogens that target the viral glycan shield for development of an effective HIV-1 vaccine. PMID- 26277073 TI - Functional immune responses to twelve serotypes after immunization with a 23 valent pneumococcal polysaccharide vaccine in older adults. AB - BACKGROUND: The 23-valent pneumococcal polysaccharide vaccine (PPSV23) was introduced as part of the national immunization program for the elderly (>=65 years of age) in Korea on 2013. To evaluate immune responses in this population, serotype-specific anti-pneumococcal antibodies were studied with opsonophagocytic assay (OPA). METHODS: Pneumococcal vaccine-naive participants >=65 years of age were enrolled. They were divided into two groups according to their age: 30 in (65-74 years) and 32 in group (>=75 years). The functional antibody response was determined by multiplexed OPA (MOPA) for 12 serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) before and 4 weeks after vaccination with PPSV23. RESULTS: Geometric mean titers (GMTs) to all tested serotypes significantly increased in both groups after vaccination compared to those before vaccination. There were no significant differences in either the fold rise (post-vaccination to pre-vaccination) or the percentage of participants with a >=4-fold increase in OPA titers between two groups for any of the 12 serotypes. Following vaccination, GMT for serotype 9V was higher in group 1 than in group 2 (P=0.011). CONCLUSIONS: PPSV23 induces functional immune response for 12 vaccine serotypes in both age groups. Further analysis is needed for the remaining 11 serotypes in the PPSV23, in order to develop a better understanding of the immune responses induced by PPV23 in older adults. PMID- 26277074 TI - Investigating the Effects of Smoking on Young Adult Male Voice by Using Multidimensional Methods. AB - OBJECTIVES: Smoking is one of the most common harmful habits in the world, especially common among young adult male population in Turkey. The purpose of this study was to evaluate the effect of smoking on the young adults' male voice using multidimensional voice assessment methods. STUDY DESIGN: This is a case control study. METHODS: The study included 109 young adult men, 51 nonsmokers and 58 smokers between the ages of 20 and 34 years. The voice evaluation protocol consisted of voice handicap index (VHI), maximum phonation time (MPT), and perceptual, acoustic, and videostroboscopic analyses. RESULTS: A statistically significant increase for physical, physiological, and total scores of VHI was found in smokers group (P < 0.05). MPT showed significantly lower values among smokers (P < 0.05). There were no significant changes in perceptual analysis of voice samples between smoker and nonsmoker groups. There were no significant changes in any of the acoustic parameters between smoker and nonsmoker groups. Results of videostroboscopic analysis showed significant relationships between smoking and increased vocal fold erythema (P < 0.05). In addition, significantly asymmetry, amplitude, and periodicity abnormality of vocal fold movements were observed in smoker group during phonation (P < 0.05). CONCLUSIONS: The results of this study indicate that observable signs of laryngeal irritation and disturbed phonatory physiology occur even in young adults with relatively brief smoking habits. Subjective symptoms of smoking on voice appear to occur earlier than objective findings. PMID- 26277075 TI - Spatiotemporal Quantification of Vocal Fold Vibration After Exposure to Superficial Laryngeal Dehydration: A Preliminary Study. AB - OBJECTIVES: The aim of the study was to evaluate the effects of a superficial laryngeal dehydration challenge on vocal fold vibration in young healthy adults using high-speed video imaging. SUBJECTS AND METHODS: In this prospective study, the effects of a 60-minute superficial laryngeal dehydration challenge on spatial (speed quotient, amplitude quotient) and temporal measures (jitter percentage, vibratory onset time) of vocal fold vibration and phonation threshold pressure (PTP) were evaluated in 10 (male = 4, female = 6) vocally normal adults (21-29 years). All measures except the vibratory onset time were measured at the 10 (low) and 80 (high) percent level of their pitch range. The vibratory onset time was obtained at habitual pitch and loudness level. Superficial laryngeal dehydration was induced by oral breathing in low ambient humidity. Prechallenge and postchallenge differences were statistically investigated using t tests with Bonferroni correction. RESULTS: The speed quotient at low-pitch phonation significantly decreased after oral breathing of low ambient humidity. Other spatiotemporal measures and PTP at low and high pitch were not significant after challenge. CONCLUSIONS: Results from this initial study have implications for the use of high-speed video imaging to detect and quantify the subtle changes in vocal fold vibrations after superficial dehydration in healthy individuals. Preliminary findings indicate that superficial dehydration in healthy individuals results in spatial deviations at low pitch. However, further studies are warranted to identify additional spatiotemporal changes in vocal fold vibration after superficial dehydration in normal and disordered populations. PMID- 26277076 TI - Erratum to: The Preventive Effects of Posterior Pericardiotomy with Intrapericardial Tube on the Development of Pericardial Effusion, Atrial Fibrillation, and Acute Kidney Injury after Coronary Artery Surgery: A Prospective, Randomized, Controlled Trial. PMID- 26277077 TI - Conflicts, Compromises, and Common Sense. PMID- 26277078 TI - Valve-in-Valve Procedures in Failing Biological Xenografts Using a Novel Balloon Expandable Device: Experience in Aortic, Mitral, and Tricuspid Positions. AB - Background Valve-in-valve (ViV) procedures for degenerated bioprostheses are an alternative for the standard of care in an aging population. Several reports showed that the Edwards Sapien XT (Edwards Lifesciences Co., Irvine, California, United States) transcatheter heart valve (THV) can be used in aortic, mitral, and tricuspid position for ViV procedures. No published case series for different valve positions exist regarding suitability of the new Edwards Sapien 3 (Edwards Lifesciences Co.) THV for this purpose. Especially, the increased stent height compared with the XT and the newly added polyethylene terephthalate cuff is of potential concern in ViV interventions. Herein, we report six cases of ViV procedures with the Edwards Sapien 3 THV with a focus on technical considerations. Methods and Results Between October 2013 and November 2014, six ViV procedures with the Edwards Sapien 3 THV were performed. Four implants were done in aortic, one in mitral, and one in tricuspid position. All procedures were performed successfully without any complications. Fluoroscopy and echocardiography confirmed an adequate position and function without any paravalvular or transvalvular leakage or elevated transvalvular gradients in any case. Conclusion Preliminary experience suggests, ViV procedures with the Edwards Sapien 3 THV are safe and reliable. The outer polyethylene terephthalate cuff, for enhanced paravalvular sealing, led to a good outcome, concerning PVL in ViV procedures without resulting in elevated transvalvular gradients. This was even the case in a mildly undersized THV when compared with the internal diameter of the surgical bioprosthesis. The central radiopaque positioning marker and the fine adjustment wheel allow for accurate positioning within degenerated bioprostheses. The increased stent height, compared with the Sapien XT, led to no complications, especially in mitral position. In bioprostheses without any fluoroscopic landmarks, a balloon valvuloplasty may be necessary to identify the appropriate deployment position. PMID- 26277079 TI - Body Mass Index as a Prognostic Factor in Resected Lung Cancer: Obesity or Underweight, Which Is the Risk Factor? AB - BACKGROUND: In general, obesity is thought to be associated with increased surgical mortality and morbidity. On the other hand, low body mass index (BMI) has recently been reported as a poor prognostic factor for surgical candidates. This study investigated the effect of BMI on lung surgery. METHODS: A retrospective study was conducted on 1,518 consecutive patients who had malignant pulmonary tumors resected between February 2008 and March 2013. BMI was used to classify patients according to the World Health Organization definition: BMI < 18.5: underweight (UW); BMI 18.5 to <25: normal weight (NW); BMI 25 to <30: overweight (OW); and BMI >= 30: obese (OB). We defined surgical resection-related mortality as any patient who died within 90 days after resection or while in the hospital. We analyzed morbidity and surgical resection-related mortality, and logistic regression analysis was used to identify predictors for surgical resection-related mortality. RESULTS: Among the four groups, the incidence of cerebrovascular complications was 1.5% in UW, 0.4% in NW, 0% in OW, and 0% in OB, and that of pulmonary complications was 13.1% in UW, 8.4% in NW, 7.3% in OW, and 7.6% in OB. Surgical resection-related mortality was 2.9% in UW, 0.6% in NW, 1.7% in OW, and 0% in OB. Multivariate analysis revealed underweight, diffusing capacity of the lung for carbon monoxide, and male sex as the significant predictors. CONCLUSIONS: In this study, low BMI was an independent risk factor for mortality, and the incidence of cerebrovascular and pulmonary complications tended to be higher in patients with low BMI than in obese patients. Underweight patients should be closely monitored following pulmonary resection. PMID- 26277080 TI - Emerging Fixation Technique to Prevent Pectus Bar Displacement: Needlescope Assisted 3-Point Fixation. AB - BACKGROUND: Bar flipping displacement is one of the most common complications after the Nuss procedure for pectus excavatum. We evaluated the results of a modified Nuss procedure with needlescope-assisted bar fixation. METHODS: The records of 41 patients with pectus excavatum who underwent single pectus bar insertion with the Nuss procedure between July 2011 and August 2014 were retrospectively reviewed. The patients were divided into two groups: those who did not undergo 3-point fixation (group A) and those who did undergo 3-point fixation (group B). RESULTS: There were 36 male patients and 5 female patients with a mean age of 10.7 +/- 8.3 years (range: 3-36 years). The postoperative Haller index (HI) (2.61 +/- 0.42) was significantly lower than the preoperative HI (3.91 +/- 1.07; p < 0.01). The angle of the initial bar position was 5.59 +/- 7.37 degrees in group A and 8.52 +/- 9.61 degrees in group B, with no significant difference between the groups (p > 0.05). The rate of reoperation to correct bar displacement was lower in group B (3.3%) than in group A (9.1%). CONCLUSION: Needlescope-assisted 3-point fixation of the bar was performed without an additional skin incision and showed a low rate of reoperation to correct displacement of the pectus bar. PMID- 26277081 TI - Electrocatalytic reduction of bromate based on Pd nanoparticles uniformly anchored on polyaniline/SBA-15. AB - A nano-composite electrocatalyst of Pd nanoparticles (Pd-NPs) anchored on polyaniline (PANI) supported by mesoporous SBA-15 (Pd-NPs/PANI/SBA-15), was synthesized using an in situ chemical method. Transmission electron microscopy showed that the Pd-NPs were homogeneously dispersed. Fourier-transform infrared and X-ray photoelectron spectroscopies confirmed that the Pd-NPs in the metallic state (Pd(0)) were predominantly immobilized on nitrogen sites in the PANI chains. The electrochemical performance of Pd-NPs/PANI/SBA-15 for electrocatalytic reduction of bromate (BrO3(-)) in an acidic medium was investigated by cyclic voltammetry (CV) and amperometric measurement. The reduction peak in the CV curves in the region 0.12 to -0.22V (vs. SCE) corresponded to response of BrO3(-) electroreduction, and the reduction peak current was well fitted linearly to the BrO3(-) concentration. It is proposed that the bromate ions diffuse to the Pd-NPs active sites and then the electrocatalytic reduction occurred with the H(+) doped in PANI. Furthermore, by amperometric measurement, Pd-NPs/PANI/SBA-15 showed relatively high sensitivity with respect to BrO3(-) concentration in the range of 8MUmolL(-1) to 40mmolL(-1). Continuous CV for 200 cycles proved that Pd-NPs/PANI/SBA-15 had excellent electrocatalytic stability. These results show that Pd-NPs/PANI/SBA-15 is effective for electrocatalytic reduction of BrO3(-) and has great potential for the fabrication of BrO3(-) electrochemical sensor. PMID- 26277082 TI - Recent advances in 3D SEM surface reconstruction. AB - The scanning electron microscope (SEM), as one of the most commonly used instruments in biology and material sciences, employs electrons instead of light to determine the surface properties of specimens. However, the SEM micrographs still remain 2D images. To effectively measure and visualize the surface attributes, we need to restore the 3D shape model from the SEM images. 3D surface reconstruction is a longstanding topic in microscopy vision as it offers quantitative and visual information for a variety of applications consisting medicine, pharmacology, chemistry, and mechanics. In this paper, we attempt to explain the expanding body of the work in this area, including a discussion of recent techniques and algorithms. With the present work, we also enhance the reliability, accuracy, and speed of 3D SEM surface reconstruction by designing and developing an optimized multi-view framework. We then consider several real world experiments as well as synthetic data to examine the qualitative and quantitative attributes of our proposed framework. Furthermore, we present a taxonomy of 3D SEM surface reconstruction approaches and address several challenging issues as part of our future work. PMID- 26277083 TI - Quantifying mean inner potential of ZnO nanowires by off-axis electron holography. AB - Off-axis electron holography has been used to quantitatively determine the mean inner potential of ZnO. [0001] grown ZnO nanowires with hexagonal cross-sections were chosen as our samples because the angle between the adjacent surfaces is 120 degrees , as confirmed by electron tomography, so the entire geometry of the nanowire could be precisely determined. The acceleration voltage of the transmission electron microscope was accurately calibrated by convergent beam electron diffraction (CBED)-higher-order Laue-zone (HOLZ) analyses. ZnO nanowires were tilted away from zone-axis to avoid strong dynamical diffraction effect, and the tilting angles were determined by CBED patterns. Our experimental data found a mean inner potential of ZnO as 14.30+/-0.28 V. PMID- 26277084 TI - Three-dimensional microstructural characterization of porous cubic zirconia. AB - A set of cubic zirconia samples were investigated using 3-dimensional electron backscatter diffraction (3D EBSD) to analyze the grain structure, grain boundary networks and pore morphology. 3D EBSD is a variation of conventional EBSD, whereby a focused ion beam (FIB) is used in a dual beam scanning electron microscope (SEM) i.e. FIB-SEM to mill away material and to create 'serial sections' through the material being analyzed. Each new surface revealed is subject to an EBSD scan, which continues sequentially until a desired volume of material has been removed. In this manner, many consecutive 2D EBSD scans can be rendered in 3D to gain a greater insight of microstructural features and parameters. The three samples were examined in order to determine the effect of differences in the manufacturing process used for each. For each sample, a volume of ca. 15,000 MUm(3) was studied. The analysis of several microstructure parameters revealed a strong dependence on manufacturing conditions. Subsequently, the results of 3D EBSD analysis were compared to conventional 2D EBSD. Significant differences between the values of microstructure parameters determined by 2D and 3D EBSD were observed. PMID- 26277085 TI - Taking a bite: Amoebic trogocytosis in Entamoeba histolytica and beyond. AB - Entamoeba histolytica is a diarrheal pathogen with the ability to cause profound host tissue damage. This organism possesses contact-dependent cell killing activity, which is likely to be a major contributor to tissue damage. E. histolytica trophozoites were recently shown to ingest fragments of living human cells. It was demonstrated that this process, termed amoebic trogocytosis, contributes to cell killing. Recent advances in ex vivo and 3-D cell culture approaches have shed light on mechanisms for tissue destruction by E. histolytica, allowing amoebic trogocytosis to be placed in the context of additional host and pathogen mediators of tissue damage. In addition to its relevance to pathogenesis of amoebiasis, an appreciation is emerging that intercellular nibbling occurs in many organisms, from protozoa to mammals. PMID- 26277086 TI - From Heart Failure to Highly Unsaturated Fatty Acid Deficiency and Vice Versa: Bidirectional Heart and Liver Interactions. AB - BACKGROUND: In several trials, beneficial prognostic effects of highly unsaturated fatty acids (HUFAs) in heart failure were shown. Because other studies showed no incremental benefit in nearly preserved cardiac function, the question arises, whether the degree of cardiac dysfunction is involved. It is hypothesized that increased left ventricular (LV) wall stress affects the endogenous hepatic HUFA metabolism, which in turn exhibits adverse cardiac consequences. METHODS: Cardiac magnetic resonance imaging was performed in 30 patients with suspected cardiomyopathy. The serum fatty acid profile was assessed using gas chromatography/mass spectrometry. RESULTS: Docosahexaenoic acid (DHA; P = 0.002) and eicosapentaenoic acid (EPA; by trend) levels were decreased in patients with reduced LV ejection fraction (<= 50%) or LV dilatation (>= 90 mL/m(2)). Decreased DHA (P = 0.003) and EPA (P = 0.022) levels were associated with a reduced LV ejection fraction. Decreased DHA level was correlated with increased end-diastolic (P = 0.047) and end-systolic LV wall stress (P = 0.001). Pseudocholinesterase activity was inversely correlated with end-diastolic (P = 0.020) and end-systolic LV wall stress (P = 0.025). CONCLUSIONS: DHA level was significantly reduced in heart failure. Similar, but less pronounced effects were found for EPA and arachidonic acid by trend. Increased LV wall stress was correlated with a reduced DHA level. Increased LV wall stress exhibits various adverse consequences (eg, increased oxygen consumption, favouring of arrhythmias, and an unfavourable remodelling). The increase of wall stress was paralleled by reduced HUFA level. Increased LV wall stress was correlated with reduced pseudocholinesterase, which is suggestive of hepatic congestion (ie, a cardiohepatic syndrome, involved in the altered fatty acid profile in heart failure) and has major consequences regarding the dose-efficacy of HUFA treatment. PMID- 26277087 TI - Antecubital vs Femoral Venous Access for Right Heart Catheterization: Benefits of a Flashback. AB - BACKGROUND: Although rare, complications of right heart catheterization (RHC) are usually related to the access site. Antecubital venous access for RHC allows immediate ambulation and may reduce access-site complications, but data on this approach are scarce. METHODS: Our study prospectively collected comprehensive data from consecutive RHCs performed at our academic center between February 2010 and August 2013. Demographic, procedural, and in-hospital outcomes were compared between patient groups defined by antecubital and femoral approaches. RESULTS: A total of 1007 RHC procedures was performed; 895 (88.9%) were performed through an antecubital approach and 112 (11.1%) were performed through a femoral approach. Antecubital attempts were successful in 92.8% of the clinically eligible patients. The antecubital approach was associated with a shorter procedure duration and fluoroscopy time as well as a lower radiation dose (P < 0.001 for all) compared with femoral access. Radiation dose and fluoroscopy time were significantly reduced (P < 0.001 for both) when antecubital procedures were performed by experienced operators compared with trainees. Periprocedural complications occurred in 8 patients (0.8%) (leading to prolonged hospitalization in only 1 patient in the femoral group). Access-site hematoma occurred more frequently in the femoral group (P < 0.001). CONCLUSIONS: An antecubital venous approach is a feasible alternative to femoral venous access for RHC. Shorter fluoroscopy time, lower radiation dose, and fewer access-site hematomas with this approach argue for its preferential use when possible and performed in an experienced centre. PMID- 26277088 TI - Minimally Invasive Repair of Partial Atrioventricular Canal Defect. AB - Percutaneous techniques offer patients with anatomically suitable secundum atrial septal defects a less invasive treatment option; however, repair of more complex atrial septal defects are still performed via sternotomy. An endoscopic, right minithoracotomy approach has demonstrated efficacy and safety in complex mitral valve repair and might be a more cosmetically appealing alternative, particularly in young adult patients. We describe a patient with partial atrioventricular canal defect and left atrioventricular valve insufficiency who underwent successful minimally invasive, endoscopic repair of this defect. PMID- 26277089 TI - Is Aortic Valve Repair Reproducible? Analysis of the Learning Curve for Aortic Valve Repair. AB - BACKGROUND: Aortic valve (AV) preservation and repair, although effective, is performed in a limited number of centres. Lack of wider application might be due to challenges in dissemination of tacit surgical knowledge. We examined the learning curve in 2 centres that initiated dedicated programs in AV repair. METHODS: Prospectively collected data on the first 100 (cohort A) and 150 consecutive patients (cohort B) who underwent AV repair surgery were analyzed. Safety end points included mortality, myocardial infarction or stroke, early AV repeat surgery, re-exploration for bleeding, or pacemaker implantation. Efficiency was assessed according to aortic crossclamp and cardiopulmonary bypass times. Efficacy parameters included residual aortic insufficiency or stenosis. Indices of case complexity included presence of severe aortic insufficiency, nontrileaflet AV, and associated cardiac procedures. Each cohort was divided into 3 equal tertiles (T1, T2, and T3). RESULTS: Early mortality was <= 1% in both cohorts. In cohort A, a total of 12 safety events occurred with a significant reduction in incidence over the tertiles (18%, 15%, and 3%, in T1, T2, and T3, respectively; P = 0.05). In cohort B, 20 safety events occurred in 18 patients with a trend toward reduction of incidence over tertiles (20%, 12%, and 8%, in T1, T2, and T3, respectively; P = 0.14). aortic crossclamp and cardiopulmonary bypass times decreased significantly after T2 in cohort A and T1 in cohort B (P < 0.01). Intraoperative procedural efficacy was similar across tertiles in both cohorts. CONCLUSIONS: Procedural safety and efficiency improves with experience whereas efficacy is consistent over time. AV repair is reproducible and appears to have a learning curve of approximately 40-60 cases. PMID- 26277090 TI - A Randomized Controlled Trial of Allopurinol in Patients With Peripheral Arterial Disease. AB - BACKGROUND: Patients with peripheral arterial disease (PAD) are limited by intermittent claudication in the distance they can walk. Allopurinol has been shown in coronary arterial disease to prolong exercise before angina occurs, likely by prevention of oxygen wastage in tissues and reduction of harmful oxidative stress. METHODS: In this study we evaluated whether allopurinol could prolong the time to development of leg pain in participants with PAD. In a double blind, randomized controlled clinical trial participants were randomized to receive either allopurinol 300 mg twice daily or placebo for 6 months. The primary outcome was change in exercise capacity on treadmill testing at 6 months. Secondary outcomes were 6-minute walking distance, Walking Impairment Questionnaire, SF-36 questionnaire, flow-mediated dilatation, and oxidized low density lipoprotein. Outcome measures were repeated midstudy and at the end of study. The mean age of the 50 participants was 68.4 +/- 1.2 years with 39 of 50 (78%) male. RESULTS: Five participants withdrew during the study (2 active, 3 placebo). There was a significant reduction in uric acid levels in those who received active treatment of 52.1% (P < 0.001), but no significant change in either the pain-free or the maximum walking distance. Other measures of exercise capacity, blood vessel function, and the participants' own assessment of their health and walking ability also did not change during the course of the study. CONCLUSIONS: Although allopurinol has been shown to be of benefit in a number of other diseases, in this study there was no evidence of any improvement after treatment in patients with PAD. PMID- 26277091 TI - The Effect of Bleeding Risk and Frailty Status on Anticoagulation Patterns in Octogenarians With Atrial Fibrillation: The FRAIL-AF Study. AB - BACKGROUND: Older adults are at increased risk of atrial fibrillation (AF), its thromboembolic complications, and bleeding. A significant percentage of octogenarians do not receive anticoagulation therapy. The objective of this study was to investigate the effect of thromboembolic risk, bleeding risk, and frailty on the anticoagulation status of octogenarians hospitalized with AF. METHODS: A cross-sectional study was conducted in 682 hospitalized patients aged 80 years and older with AF or atrial flutter in Montreal, Quebec. Consumption of warfarin or a new oral anticoagulant was documented. Medical record data were used to determine each patient's frailty status using the Clinical Frailty Scale (CFS) and to evaluate the risk of stroke (CHADS2 [Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke/Transient Ischemic Attack]) and bleeding (HAS BLED [Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (> 65 years) Drugs/alcohol concomitantly]). Univariable and multivariable logistic regression analyses were used to examine the effect of frailty status and the risk of stroke and bleeding on the probability of receiving anticoagulation therapy. RESULTS: Seventy percent of octogenarians with AF received anticoagulation therapy (n = 475). A high risk of stroke (CHADS2 = 3 compared with CHADS2 = 1, odds ratio [OR], 3.58; 95% confidence interval [CI], 1.09-11.77), and the absence of severe frailty (CFS < 7; OR, 3.41; 95% CI, 1.84-6.33) were independently associated with anticoagulant use in multivariable analyses. A high risk of bleeding (HAS-BLED score >= 3; OR, 0.33; 95% CI, 0.12-0.86) was associated with the absence of anticoagulation. CONCLUSIONS: Our study suggests a higher prevalence of appropriate anticoagulation among octogenarians with AF than reported in previous studies. Further work is needed to develop and disseminate tools to optimize the use of anticoagulants in this high-risk population. PMID- 26277092 TI - Contrast-Induced Nephropathy: From Pathophysiology to Preventive Strategies. AB - Contrast-induced nephropathy (CIN) is a frequent cause of acute kidney injury in hospitalized patients. CIN is most commonly defined as either an absolute (>= 0.5 mg/dL; >= 44 MUmol/L) or relative (>= 25%) increase in serum creatinine levels at 48-72 hours after exposure to iodinated contrast media (CM). Its occurrence is associated with worsened clinical outcomes. Patients undergoing cardiac catheterization and percutaneous coronary intervention are particularly vulnerable to CIN. The complex pathophysiology of CIN involves different mechanisms, such as vasoconstriction, oxidative stress, medullary ischemia, and the direct toxic effects of CM. In CIN pathophysiology, both patient-related and procedure-related risk factors have been identified. The risk for CIN can be reliably estimated with clinical scores such as that proposed by Mehran. Because no definitive treatment exists for CIN, the most effective strategy remains prevention. Several interventions have been investigated--from hydration to various pharmacologic agents and mechanical devices. In this state-of-the-art article, we review the pathophysiology, diagnosis, risk stratification, and preventive strategies for CIN. PMID- 26277093 TI - Physiological enzymology: The next frontier in understanding protein structure and function at the cellular level. AB - Historically, the study of proteins has relied heavily on characterizing the activity of a single purified protein isolated from other cellular components. This classic approach allowed scientists to unambiguously define the intrinsic kinetic and chemical properties of that protein. The ultimate hope was to extrapolate this information toward understanding how the enzyme or receptor behaves within its native cellular context. These types of detailed in vitro analyses were necessary to reduce the innate complexities of measuring the singular activity and biochemical properties of a specific enzyme without interference from other enzymes and potential competing substrates. However, recent developments in fields encompassing cell biology, molecular imaging, and chemical biology now provide the unique chemical tools and instrumentation to study protein structure, function, and regulation in their native cellular environment. These advancements provide the foundation for a new field, coined physiological enzymology, which quantifies the function and regulation of enzymes and proteins at the cellular level. In this Special Edition, we explore the area of Physiological Enzymology and Protein Function through a series of review articles that focus on the tools and techniques used to measure the cellular activity of proteins inside living cells. This article is part of a Special Issue entitled: Physiological Enzymology and Protein Functions. PMID- 26277094 TI - Behavioral signs of pain and functional impairment in a mouse model of osteogenesis imperfecta. AB - Osteogenesis imperfecta (OI) is a congenital disorder caused most often by dominant mutations in the COL1A1 or COL1A2 genes that encode the alpha chains of type I collagen. Severe forms of OI are associated with skeletal deformities and frequent fractures. Skeletal pain can occur acutely after fracture, but also arises chronically without preceding fractures. In this study we assessed OI associated pain in the Col1a1Jrt/+ mouse, a recently developed model of severe dominant OI. Similar to severe OI in humans, this mouse has significant skeletal abnormalities and develops spontaneous fractures, joint dislocations and vertebral deformities. In this model, we investigated behavioral measures of pain and functional impairment. Significant hypersensitivity to mechanical, heat and cold stimuli, assessed by von Frey filaments, radiant heat paw withdrawal and the acetone tests, respectively, were observed in OI compared to control wildtype littermates. OI mice also displayed reduced motor activity in the running wheel and open field assays. Immunocytochemical analysis revealed no changes between OI and WT mice in innervation of the glabrous skin of the hindpaw or in expression of the pain-related neuropeptide calcitonin gene-related protein in sensory neurons. In contrast, increased sensitivity to mechanical and cold stimulation strongly correlated with the extent of skeletal deformities in OI mice. Thus, we demonstrated that the Col1a1Jrt/+ mouse model of severe OI has hypersensitivity to mechanical and thermal stimuli, consistent with a state of chronic pain. PMID- 26277095 TI - Integrating microbial and host transcriptomics to characterize asthma-associated microbial communities. AB - BACKGROUND: The relationships between infections in early life and asthma are not completely understood. Likewise, the clinical relevance of microbial communities present in the respiratory tract is only partially known. A number of microbiome studies analyzing respiratory tract samples have found increased proportions of gamma-Proteobacteria including Haemophilus influenzae, Moraxella catarrhalis, and Firmicutes such as Streptococcus pneumoniae. The aim of this study was to present a new approach that combines RNA microbial identification with host gene expression to characterize and validate metagenomic taxonomic profiling in individuals with asthma. METHODS: Using whole metagenomic shotgun RNA sequencing, we characterized and compared the microbial communities of individuals, children and adolescents, with asthma and controls. The resulting data were analyzed by partitioning human and microbial reads. Microbial reads were then used to characterize the microbial diversity of each patient, and potential differences between asthmatic and healthy groups. Human reads were used to assess the expression of known genes involved in the host immune response to specific pathogens and detect potential differences between those with asthma and controls. RESULTS: Microbial communities in the nasal cavities of children differed significantly between asthmatics and controls. After read count normalization, some bacterial species were significantly overrepresented in asthma patients (Wald test, p-value < 0.05), including Escherichia coli and Psychrobacter. Among these, Moraxella catarrhalis exhibited ~14-fold over abundance in asthmatics versus controls. Differential host gene expression analysis confirms that the presence of Moraxella catarrhalis is associated to a specific M. catarrhalis core gene signature expressed by the host. CONCLUSIONS: For the first time, we show the power of combining RNA taxonomic profiling and host gene expression signatures for microbial identification. Our approach not only identifies microbes from metagenomic data, but also adds support to these inferences by determining if the host is mounting a response against specific infectious agents. In particular, we show that M. catarrhalis is abundant in asthma patients but not in controls, and that its presence is associated with a specific host gene expression signature. PMID- 26277096 TI - Diosgenin regulates adipokine expression in perivascular adipose tissue and ameliorates endothelial dysfunction via regulation of AMPK. AB - Perivascular adipose tissue (PVAT) has been recognized as an active contributor to vascular function due to its paracrine effects on cells contained within vascular wall. The present study was designed to investigate the effect of diosgenin on adipokine expression in PVAT with emphasis on the regulation of endothelial function. Palmitic acid (PA) stimulation induced inflammation and dysregulation of adipokine expression in PVAT. Diosgenin treatment inhibited IKKbeta phosphorylation and downregulated mRNA expressions of proinflammatory cytokines/proteins including tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), monocyte chemoattractant protein (MCP-1), and inducible nitric oxide synthase (iNOS), while reduced gene expressions for adiponectin, PPARgamma, and arginase 1 (Arg-1) were reversed by diosgenin treatment. Diosgenin enhanced AMPK phosphorylation under basal and inflammatory conditions in PVAT, whereas knockdown of AMPK by SiRNA diminished its modulatory effect, indicating that diosgenin inhibited inflammation in an AMPK-dependent manner. We prepared conditioned medium from PA-stimulated PVAT to induce endothelial dysfunction and found that pre-treatment of PVAT with diosgenin effectively restored the loss of ACh-induced vasodilation and increased eNOS phosphorylation in rat aorta. High fat diet feeding in rats induced inflammation in PVAT and the impairment of endothelium-dependent vasodilation, whereas these alterations were prevented by oral administration of diosgenin at doses of 20 and 40 mg/kg. In conclusion, the obtained data showed that diosgenin ameliorated inflammation-associated adipokine dysregulation, and thereby prevented endothelial dysfunction. Our findings would shed a novel insight into the potential mechanism by which diosgenin protected endothelial function against inflammatory insult. PMID- 26277098 TI - Morphological changes after radiosurgery for mesial temporal lobe epilepsy. AB - BACKGROUND: To review our experience with morphological developments during the long-term follow-up of patients treated by Gamma Knife radiosurgery for mesial temporal lobe epilepsy. METHOD: Between 1995 and 1999, we treated 14 patients with marginal doses of 24 Gy (n = 6) and 18-20 Gy (n = 8). Nine of these were operated on for insufficient seizure control. We reviewed seizure outcome and magnetic resonance images in both operated and unoperated patients and also re examined histopathology specimens. RESULTS: Of the nine operated patients, two were Engel IIIA, one was IVA, five were IVB, and one was Engel IVC prior to surgery. At their final visit, five cases had become Engel class IA, one patient was ID, and two were IIC. In one patient the follow-up was not long enough for classification. Of the five unoperated patients, one was Engel class IB, one was IIIA, one IIB and one IVB at their final visit. Radionecrosis developed in 11 patients, occurring more often and earlier in those treated with higher doses. Collateral edema reached outside the temporal lobe in six patients, caused uncal herniation in two and intracranial hypertension in three. During longer follow up, postnecrotic pseudocysts developed in 9 patients, and postcontrast enhancement persisted for 2.5-16 years after GKRS in all 14 patients. In five of them we detected its progression between 2 and 16 years after treatment. Signs of neoangiogenesis were found in two patients and microbleeds could be seen in five. Histopathology revealed blood vessel proliferation and macrophage infiltration. CONCLUSIONS: Early delayed complications and morphological signs suggesting a risk of development of late delayed complications are frequent after radiosurgery for mesial temporal lobe epilepsy. Together with its unproven antiseizure efficacy, these issues should be taken into account when planning future studies of this method. PMID- 26277099 TI - Survival of breast cancer patients with synchronous or metachronous central nervous system metastases. AB - BACKGROUND: Central nervous system (CNS) metastases represent a devastating complication for advanced breast cancer patients. This observational study examines the influence of patient, tumour and treatment characteristics on overall survival after synchronous or metachronous CNS metastases. METHODS: Information on 992 breast cancer patients with CNS metastases (whose primary tumour was diagnosed between 2004 and 2010) was retrieved from the Netherlands Cancer Registry (NCR). Overall survival was calculated from the date of CNS metastatic diagnosis, and the impact of prognostic factors on survival was assessed using univariate and multivariate extended Cox-regression models. RESULTS: We identified 165 patients with synchronous and 827 patients with metachronous CNS metastases. The majority of patients (88%) presented with brain metastases only, 12% had leptomeningeal metastases. Overall median survival was 5.0 months. Non-triple-negative breast cancer and systemic therapy were associated with improved survival in both groups. In patients with synchronous CNS metastases, surgery for the primary tumour and the metastases also improved survival. In patients with metachronous metastases, younger age (<50 years), lower initial tumour stage (I), ductal carcinoma, a prolonged time interval until diagnosis of CNS metastasis (>1 year), and absence of extracranial metastases were associated with improved survival. Metastasectomy and radiation therapy did not provide benefit beyond the first six months. CONCLUSIONS: No difference in survival was established between synchronous and metachronous CNS metastases. Triple-negative disease is prognostically unfavourable in both groups, while those receiving treatment have a better outcome. Metastasectomy and radiotherapy improve survival within the first six months, and additional benefit may be derived from systemic therapy. PMID- 26277097 TI - Structural and functional characterization of aromatase, estrogen receptor, and their genes in endocrine-responsive and -resistant breast cancer cells. AB - Aromatase and estrogen receptor alpha (ER) are two key proteins for the proliferation of endocrine-responsive and -resistant breast cancers. Aromatase is an enzyme involved in the conversion of androgen (such as testosterone) to estrogen (such as 17beta-estradiol). It is also a very effective therapeutic target for the treatment of endocrine-responsive breast cancer. Comparing endocrine-responsive and -resistant breast cancer, aromatase protein levels do not change significantly. Aromatase activity; however, can be increased via PI3K/Akt/IGFR signaling pathways in endocrine resistant cells. The activity of aromatase has been reported to be modulated by phosphorylation. The ER is an important steroid nuclear receptor in the proliferation of both endocrine responsive and -resistant cells. Although the mutation or amplification of ER can cause endocrine resistance, it is not commonly found. Some point mutations and translocation events have been characterized and shown to promote estrogen independent growth. Phosphorylation by cross-talk with growth factor pathways is one of the main mechanisms for ligand-independent activation of ER. Taken together, both ER and aromatase are important in ER-dependent breast cancer and the development of endocrine resistance. PMID- 26277100 TI - Improved inter-observer agreement of an expert review panel in an oncology treatment trial--Insights from a structured interventional process. AB - PURPOSE: Oncologic imaging is a key for successful cancer treatment. While the quality assurance (QA) of image acquisition protocols has already been focussed, QA of reading and reporting offers still room for improvement. The latter was addressed in the context of a prospective multicentre trial on fluoro deoxyglucose (FDG)-positron-emission tomography (PET)/CT-based chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: An expert panel was prospectively installed performing blinded reviews of mediastinal NSCLC involvement in FDG-PET/CT. Due to a high initial reporting inter-observer disagreement, the independent data monitoring committee (IDMC) triggered an interventional harmonisation process, which overall involved 11 experts uttering 6855 blinded diagnostic statements. After assessing the baseline inter-observer agreement (IOA) of a blinded re-review (phase 1), a discussion process led to improved reading criteria (phase 2). Those underwent a validation study (phase 3) and were then implemented into the study routine. After 2 months (phase 4) and 1 year (phase 5), the IOA was reassessed. RESULTS: The initial overall IOA was moderate (kappa 0.52 CT; 0.53 PET). After improvement of reading criteria, the kappa values improved substantially (kappa 0.61 CT; 0.66 PET), which was retained until the late reassessment (kappa 0.71 CT; 0.67 PET). Subjective uncertainty was highly predictive for low IOA. CONCLUSION: The IOA of an expert panel was significantly improved by a structured interventional harmonisation process which could be a model for future clinical trials. Furthermore, the low IOA in reporting nodal involvement in NSCLC may bear consequences for individual patient care. PMID- 26277101 TI - Photodynamic Diagnosis Using 5-Aminolevulinic Acid in 41 Biopsies for Primary Central Nervous System Lymphoma. AB - We evaluated the feasibility of 5-aminolevulinic acid (5-ALA)-mediated photodynamic diagnosis (PDD) in the biopsy for primary central nervous system lymphoma (PCNSL). 5-ALA (20 mg kg(-1) ) was administered orally 4 hours preoperatively. Forty-one biopsies obtained under PDD in 47 consecutive biopsies (46 patients) that were finally pathologically diagnosed as PCNSL were evaluated. Positive fluorescence was observed in 34 of those 41 biopsies (82.9%). An intraoperative pathological diagnosis (IOD) of suspected PCNSL was made in 21 of the biopsies with positive fluorescence (61.8%). However, the eight IODs in the remaining 13 biopsies (23.5%) were not correct (atypical cell, 4; high-grade glioma, 1; gliosis, 1; unremarkable, 2). In those 8 biopsies, PCNSL was confirmed by the final pathological diagnosis. There was no difference in the mean Mib-1 labeling index between the biopsies with positive fluorescence (86.5%) and those without positive fluorescence (90.0%). IOD was not performed in 6 biopsies; however, 5 of those biopsies (83.3%) showed positive fluorescence and were finally pathologically diagnosed as PCNSL. Use of PDD in biopsies for patients with suspected PCNSL is a reliable way of obtaining specimens of adequate quality for the final pathological diagnosis and may lead to improved diagnostic yield in the biopsy of PCNSL. PMID- 26277102 TI - Novel mutations and polymorphisms in the CFTR gene associated with three subtypes of congenital absence of vas deferens. AB - OBJECTIVE: To study the new genotypes in congenital absence of vas deferens (CAVD) and the correlation with different phenotypes, and to investigate the pathogenesis of the disease based on bioinformatics analysis. DESIGN: Case control study. SETTING: University-affiliated tertiary teaching hospital. PATIENT(S): Nineteen patients with CAVD and azoospermia. The time period of the study was from May 2013 to April 2014. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Sanger sequencing was performed in the coding regions and intron-exon boundaries of the cystic fibrosis transmembrane regulator CFTR gene on the polymerase chain reaction (PCR) products. Mutations/variations were identified and compared with the control subjects, and bioinformatics analysis searched in the dbSNP and 1000 Genomes Project. Functional effects of the novel mutations were predicted. Structural modeling of the wild and mutant proteins was also performed. RESULT(S): A total of 8 mutations were identified in 12 patients, 4 of which were novel (c.4433C>G, c.3469-3C>A, c.1357delT, and c.3407C>T). The mutation c.4433C>G occurred in the PSD-95/DLG/ZO-1 (PDZ)-binding motif in the CFTR protein, which was predicted to disrupt the interaction between CFTR and CFTR-associated ligand (CAL). Another missense mutation, c.3407C>T, was predicted to damage and destroy the transmembrane adenosine triphosphate (ATP)-binding cassette domain. The splicing mutation, c.3469-3C>A, was predicted to truncate exon 22 by Human Splicing Finder. The frameshift mutation, c.1357delT, was predicted to introduce a premature stop codon at position 453 and lead to 1,012 amino acids truncation at the carboxyl terminus of the CFTR protein. CONCLUSION(S): This study illustrates the significance of whole exon sequencing of the CFTR gene in patients with CAVD. It is essential for determining the pathogenesis of novel mutations using bioinformatics analysis and to identify correlation between new genotypes and phenotypes. PMID- 26277103 TI - Novel FGFR1 mutations in Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism: evidence for the involvement of an alternatively spliced isoform. AB - OBJECTIVE: To determine the prevalence of fibroblast growth factor receptor 1 (FGFR1) mutations and their predicted functional consequences in patients with idiopathic hypogonadotropic hypogonadism (IHH). DESIGN: Cross-sectional study. SETTING: Multicentric. PATIENT(S): Fifty unrelated patients with IHH (21 with Kallmann syndrome and 29 with normosmic IHH). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Patients were screened for mutations in FGFR1. The functional consequences of mutations were predicted by in silico structural and conservation analysis. RESULT(S): Heterozygous FGFR1 mutations were identified in six (12%) kindreds. These consisted of frameshift mutations (p.Pro33-Alafs*17 and p.Tyr654*) and missense mutations in the signal peptide (p.Trp4Cys), in the D1 extracellular domain (p.Ser96Cys) and in the cytoplasmic tyrosine kinase domain (p.Met719Val). A missense mutation was identified in the alternatively spliced exon 8A (p.Ala353Thr) that exclusively affects the D3 extracellular domain of FGFR1 isoform IIIb. Structure-based and sequence-based prediction methods and the absence of these variants in 200 normal controls were all consistent with a critical role for the mutations in the activity of the receptor. Oligogenic inheritance (FGFR1/CHD7/PROKR2) was found in one patient. CONCLUSION(S): Two FGFR1 isoforms, IIIb and IIIc, result from alternative splicing of exons 8A and 8B, respectively. Loss-of-function of isoform IIIc is a cause of IHH, whereas isoform IIIb is thought to be redundant. Ours is the first report of normosmic IHH associated with a mutation in the alternatively spliced exon 8A and suggests that this disorder can be caused by defects in either of the two alternatively spliced FGFR1 isoforms. PMID- 26277104 TI - Synovial sarcoma is a gateway to the role of chromatin remodeling in cancer. AB - Patients afflicted with synovial sarcoma share the fate of other translocation positive sarcomas; the driver mutation for this cancer is known, yet no means to target the fusion protein SS18-SSX directly exist. Current chemotherapeutic regimens are minimally beneficial, particularly in patients with metastatic disease. SS18-SSX putatively promotes its oncogenic activity through protein protein interactions that alter genetic programs through chromatin remodeling. This review discusses the functional protein network of SS18-SSX, both wild-type and fusion protein, considers its intrinsically disordered nature, and provides insights into potential therapeutic strategies. A comprehensive overview of the clinical characteristics reveals the need for newly targeted therapeutics based upon oncogenic transformation by the fusion protein SS18-SSX. The wild-type, non fused proteins SS18 and SSX are presented including their molecular structure and biological function with regard to protein-protein interactions. The interactions of the wild-type proteins inform the oncogenic changes of the fusion protein. The SS18-SSX fusion protein and its protein interactions are described and evaluated for their biological consequences that lead to oncogenesis. This review illustrates the key protein interactions of SS18-SSX that may qualify as primary targets for small molecule-based disruption leading to the development of SS18 SSX-specific drugs. These novel targeted therapeutics may provide a specificity that ultimately improves survival while reducing morbidity of patients with synovial sarcoma. PMID- 26277105 TI - Epigenetics regulation of disease: There is more to a gene than its sequence. PMID- 26277106 TI - The urodele amphibian Pleurodeles waltl has a diverse repertoire of immunoglobulin heavy chains with polyreactive and species-specific features. AB - Urodele amphibians are an interesting model because although they possess the cardinal elements of the vertebrate immune system, their immune response is apparently subdued. This phenomenon, sometimes regarded as a state of immunodeficiency, has been attributed by some authors to limited antibody diversity. We reinvestigated this issue in Pleurodeles waltl, a metamorphosing urodele, and noted that upsilon transcripts of its IgY repertoire were as diverse as alpha transcripts of the mammalian IgA repertoire. Mu transcripts encoding the IgM repertoire were less diverse, but could confer more plasticity. Both isotypes present potential polyreactive features that may confer urodele antibodies with the ability to bind to a variety of antigens. Finally, we observed additional cysteines in CDR1 and 2 of the IGHV5 and IGHV6 domains, some of which specific to urodeles, that could allow the establishment of a disulfide bond between these CDRs. Together, these data suggest that urodele antibody diversity is not as low as previously thought. PMID- 26277107 TI - Identification of nuclear factor kappaB (NF-kappaB) binding motifs in Biomphalaria glabrata. AB - Biomphalaria glabrata acts as the intermediate host to the parasite, Schistosoma mansoni, and for this reason, the immune system of B. glabrata has been researched extensively. Several studies have demonstrated that the transcriptome profile of B. glabrata changes following exposure to a variety of pathogens, yet very little is known regarding the regulation of gene expression in this species. Nuclear factor kappaB (NF-kappaB) homologues have recently been identified in B. glabrata but few functional studies have been carried out on this family of transcription factors. The aims of this study therefore were to identify NF kappaB binding sites (kappaB motifs) in B. glabrata and examine them via functional assays. Two different kappaB motifs were predicted. Furthermore, the Rel homology domain (RHD) of a B. glabrata NF-kappaB was able to bind these kappaB motifs in EMSAs, as well as a vertebrate kappaB motif. PMID- 26277108 TI - Simultaneous depletion of Atm and Mdl rebalances cytosolic Fe-S cluster assembly but not heme import into the mitochondrion of Trypanosoma brucei. AB - ABC transporter mitochondrial 1 (Atm1) and multidrug resistance-like 1 (Mdl) are mitochondrial ABC transporters. Although Atm1 was recently suggested to transport different forms of glutathione from the mitochondrion, which are used for iron sulfur (Fe-S) cluster maturation in the cytosol, the function of Mdl remains elusive. In Trypanosoma brucei, we identified one homolog of each of these genes, TbAtm and TbMdl, which were downregulated either separately or simultaneously using RNA interference. Individual depletion of TbAtm and TbMdl led to limited growth defects. In cells downregulated for TbAtm, the enzymatic activities of the Fe-S cluster proteins aconitase and fumarase significantly decreased in the cytosol but not in the mitochondrion. Downregulation of TbMdl did not cause any change in activities of the Fe-S proteins. Unexpectedly, the simultaneous downregulation of TbAtm and TbMdl did not result in any growth defect, nor were the Fe-S cluster protein activities altered in either the cytosolic or mitochondrial compartments. Additionally, TbAtm and TbMdl were able to partially restore the growth of the Saccharomyces cerevisiae Deltaatm1 and Deltamdl2 null mutants, respectively. Because T. brucei completely lost the heme b biosynthesis pathway, this cofactor has to be obtained from the host. Based on our results, TbMdl is a candidate for mitochondrial import of heme b, which was markedly decreased in both TbMdl and TbAtm + TbMdl knockdowns. Moreover, the levels of heme a were strongly decreased in the same knockdowns, suggesting that TbMdl plays a key role in heme a biosynthesis, thus affecting the overall heme homeostasis in T. brucei. PMID- 26277109 TI - A multilevel cross-lagged structural equation analysis for reciprocal relationship between social capital and health. AB - We investigated the reciprocal relationship between individual social capital and perceived mental and physical health in the UK. Using data from the British Household Panel Survey from 1991 to 2008, we fitted cross-lagged structural equation models that include three indicators of social capital vis. social participation, social network, and loneliness. Given that multiple measurement points (level 1) are nested within individuals (level 2), we also applied a multilevel model to allow for residual variation in the outcomes at the occasion and individual levels. Controlling for gender, age, employment status, educational attainment, marital status, household wealth, and region, our analyses suggest that social participation predicts subsequent change in perceived mental health, and vice versa. However, whilst loneliness is found to be significantly related to perceived mental and physical health, reciprocal causality is not found for perceived mental health. Furthermore, we find evidence for reverse effects with both perceived mental and physical health appearing to be the dominant causal factor with respect to the prospective level of social network. Our findings thus shed further light on the importance of social participation and social inclusion in health promotion and aid the development of more effective public health policies in the UK. PMID- 26277111 TI - Outcome Measures in Bariatric Surgery. PMID- 26277110 TI - Bariatric Nutrition Guidelines for the Indian Population. AB - BACKGROUND: Bariatric surgery numbers have seen a sharp rise in India in the last decade. A country known for its undernourished population has seen economic growth and with it, greater influence of western culture and foods. The obesity epidemic is on the rise here and India is one of the 10 most obese nations of the world being second only to China in the number of type 2 diabetes. Nutritionists in India often rely on recommendations and guidelines meant for the Caucasian population. Religious and cultural practices influence the dietary habits and patterns of the Indian population to a great extent; because of which the nutritional requirements are very different. This document was put together with an aim to provide nutritionists with recommendations on how to manage the Indian bariatric patient. METHODS: A bariatric nutrition round table meeting was initiated by the Centre for Obesity and Digestive Surgery (CODS) to bring together experts in the field of bariatric nutrition to review current data on nutritional deficiencies in the morbid obese and existing post-operative deficiencies and to formulate nutritional recommendations for bariatric/metabolic surgery specific to patients from India. RESULTS: Percentage of nutritional deficiencies and reasons for the same were identified among the Indian population and recommendations were made to suit this particular population. CONCLUSION: It is recommended that all patients undergo compulsory pre-operative nutritional counseling and nutritional investigations and that nutritional follow-up be continued lifelong. In addition, long-term implications like hypoglycemia, dumping syndrome, sugar cravings, and weight regain, need to be picked up and managed efficiently. Most importantly, post-operative supplementation is a must irrespective of type of surgery. PMID- 26277112 TI - Reply to the Letter to the Editor: Citation Analysis in Bariatric Surgery. PMID- 26277113 TI - A pharmacist-led medication assessment used to determine a more precise estimation of the prevalence of complementary and alternative medication (CAM) use among ambulatory senior adults with cancer. AB - OBJECTIVES: The prevalence of complementary and alternative medication (CAM) use in senior adult oncology (SAO) patients is widely variable and little is known about whether polypharmacy (PP) and potentially inappropriate medication (PIM) use influences CAM use given the increased number of comorbidities and polypharmacy. One approach to optimize medication management is through utilization of pharmacists as part of a team-based, healthcare model. MATERIALS AND METHODS: Prevalence of CAM and factors influencing CAM use was examined in a secondary analysis of 248 patients who received an initial comprehensive geriatric oncology assessment between January 2011 and June 2013. Data was collected from electronic medical records. CAM was defined as herbal medications, minerals, or other dietary supplements, excluding vitamins. Patient characteristics influencing CAM use (e.g. comorbidities, PP and PIM use) were analyzed. RESULTS: Only 234 patients (evaluated by pharmacists) were included in the final analysis. Mean age was 79.9 years [range 61-98]; 64% women, 74% Caucasian, 87% with a solid tumor, mean comorbidities, 7.69. CAM prevalence was 26.5% (n=62) and median CAM use was 0 (range 0-10). The proportion of CAM use (1, 2, and 3) was 19.2%, 6.4%, and 0.4%, respectively. Associations with CAM use (versus no-CAM) were polypharmacy (P=0.045), vision impairment (P=0.048) and urologic comorbidities (P=0.021). CONCLUSIONS: A pharmacist-led comprehensive medication assessment demonstrated a more precise estimation of CAM prevalence in the ambulatory SAO population. CAM use was associated with polypharmacy, ophthalmic and urologic medical conditions. Integrating pharmacists into team based (geriatric and oncology) care models is an underutilized yet viable solution to optimize medication use. PMID- 26277114 TI - Identification of clinical parameters predictive of one-year survival using two geriatric tools in clinically fit older patients with hematological malignancies: Major impact of cognition. AB - BACKGROUND: Little is known about the reliability of G8 screening tool and the prognostic value of clinical parameters within the Comprehensive Geriatric Assessment (CGA) in clinically fit older patients with hematological malignancies. MATERIALS AND METHODS: This study was performed to assess the reliability of G8 as a screening tool and to determine the predictive value of CGA items in terms of 1-year overall survival (OS). G8 and CGA were proposed to 107 consecutive patients (65-89 years) with hematological malignancies assessed by their physicians as clinically fit, meaning not exhibiting geriatric syndromes and/or irreversible comorbidities significantly impairing their daily function, and thus able to receive chemotherapy. RESULTS: Out of 107 patients, 90 patients were evaluable and completed both scales; 72% and 80% were defined as "vulnerable" when evaluated with G8 (<= 14.5) or CGA (>= 2 impairments) respectively. The area under ROC-curve of G8 compared to CGA was 0.749+/-0.051. Neither G8 nor CGA total scores were predictive of 1-year OS. However, age (HR=1.105, 95% CI: 1.016-1.202; p=0.019), diagnosis (HR=5.208, 95% CI: 1.895 14.310; p=0.001) and cognitive status (HR=3.260, 95% CI: 1.043-10.194; p=0.042) were predictive of OS. CONCLUSIONS: We conclude that in our selected hematological patients: 1) the G8 score does not help selecting patients for CGA, 2) the G8 and CGA total scores do not predict OS, and 3) in addition to the age and disease itself, cognitive impairment appears to be a powerful prognostic factor. PMID- 26277116 TI - Development of a large-scale neuroimages and clinical variables data atlas in the neuGRID4You (N4U) project. AB - Exceptional growth in the availability of large-scale clinical imaging datasets has led to the development of computational infrastructures that offer scientists access to image repositories and associated clinical variables data. The EU FP7 neuGRID and its follow on neuGRID4You (N4U) projects provide a leading e Infrastructure where neuroscientists can find core services and resources for brain image analysis. The core component of this e-Infrastructure is the N4U Virtual Laboratory, which offers easy access for neuroscientists to a wide range of datasets and algorithms, pipelines, computational resources, services, and associated support services. The foundation of this virtual laboratory is a massive data store plus a set of Information Services collectively called the 'Data Atlas'. This data atlas stores datasets, clinical study data, data dictionaries, algorithm/pipeline definitions, and provides interfaces for parameterised querying so that neuroscientists can perform analyses on required datasets. This paper presents the overall design and development of the Data Atlas, its associated dataset indexing and retrieval services that originated from the development of the N4U Virtual Laboratory in the EU FP7 N4U project in the light of detailed user requirements. PMID- 26277115 TI - PKDE4J: Entity and relation extraction for public knowledge discovery. AB - Due to an enormous number of scientific publications that cannot be handled manually, there is a rising interest in text-mining techniques for automated information extraction, especially in the biomedical field. Such techniques provide effective means of information search, knowledge discovery, and hypothesis generation. Most previous studies have primarily focused on the design and performance improvement of either named entity recognition or relation extraction. In this paper, we present PKDE4J, a comprehensive text-mining system that integrates dictionary-based entity extraction and rule-based relation extraction in a highly flexible and extensible framework. Starting with the Stanford CoreNLP, we developed the system to cope with multiple types of entities and relations. The system also has fairly good performance in terms of accuracy as well as the ability to configure text-processing components. We demonstrate its competitive performance by evaluating it on many corpora and found that it surpasses existing systems with average F-measures of 85% for entity extraction and 81% for relation extraction. PMID- 26277117 TI - Holistic approach to design and implementation of a medical teleconsultation workspace. AB - While there are many state-of-the-art approaches to introducing telemedical services in the area of medical imaging, it is hard to point to studies which would address all relevant aspects in a complete and comprehensive manner. In this paper we describe our approach to design and implementation of a universal platform for imaging medicine which is based on our longstanding experience in this area. We claim it is holistic, because, contrary to most of the available studies it addresses all aspects related to creation and utilization of a medical teleconsultation workspace. We present an extensive analysis of requirements, including possible usage scenarios, user needs, organizational and security issues and infrastructure components. We enumerate and analyze multiple usage scenarios related to medical imaging data in treatment, research and educational applications - with typical teleconsultations treated as just one of many possible options. Certain phases common to all these scenarios have been identified, with the resulting classification distinguishing several modes of operation (local vs. remote, collaborative vs. non-interactive etc.). On this basis we propose a system architecture which addresses all of the identified requirements, applying two key concepts: Service Oriented Architecture (SOA) and Virtual Organizations (VO). The SOA paradigm allows us to decompose the functionality of the system into several distinct building blocks, ensuring flexibility and reliability. The VO paradigm defines the cooperation model for all participating healthcare institutions. Our approach is validated by an ICT platform called TeleDICOM II which implements the proposed architecture. All of its main elements are described in detail and cross-checked against the listed requirements. A case study presents the role and usage of the platform in a specific scenario. Finally, our platform is compared with similar systems described into-date studies and available on the market. PMID- 26277118 TI - Classifying individuals based on a densely captured sequence of vital signs: An example using repeated blood pressure measurements during hemodialysis treatment. AB - Electronic Health Records (EHRs) present the opportunity to observe serial measurements on patients. While potentially informative, analyzing these data can be challenging. In this work we present a means to classify individuals based on a series of measurements collected by an EHR. Using patients undergoing hemodialysis, we categorized people based on their intradialytic blood pressure. Our primary criteria were that the classifications were time dependent and independent of other subjects. We fit a curve of intradialytic blood pressure using regression splines and then calculated first and second derivatives to come up with four mutually exclusive classifications at different time points. We show that these classifications relate to near term risk of cardiac events and are moderately stable over a succeeding two-week period. This work has general application for analyzing dense EHR data. PMID- 26277119 TI - Communication: Antibody stability and behavior on surfaces. AB - Antibody microarrays have the potential to revolutionize molecular detection in scientific, medical, and other biosensor applications, but their current use is limited because of poor reliability. It is hypothesized that one reason for their poor performance results from strong antibody-surface interactions that destabilize the antibody structure and create steric interference for antigen recognition. Using a recently developed coarse-grain protein-surface model that has been parameterized against experimental data, antibody-surface interactions for two antibody orientations on two types of surfaces have been investigated. The results show that regardless of attachment geometry, antibodies tend to collapse onto hydrophobic surfaces and exhibit lower overall stability compared to antibodies on hydrophilic surfaces or in bulk solution. The results provide an unprecedented view into the dynamics of antibodies on surfaces and offer new insights into the poor performance exhibited by current antibody microarrays. PMID- 26277120 TI - Communication: Quantitative multi-site frequency maps for amide I vibrational spectroscopy. AB - An accurate method for predicting the amide I vibrational spectrum of a given protein structure has been sought for many years. Significant progress has been made recently by sampling structures from molecular dynamics simulations and mapping local electrostatic variables onto the frequencies of individual amide bonds. Agreement with experiment, however, has remained largely qualitative. Previously, we used dipeptide fragments and isotope-labeled constructs of the protein G mimic NuG2b as experimental standards for developing and testing amide I frequency maps. Here, we combine these datasets to test different frequency-map models and develop a novel method to produce an optimized four-site potential (4P) map based on the CHARMM27 force field. Together with a charge correction for glycine residues, the optimized map accurately describes both experimental datasets, with average frequency errors of 2-3 cm(-1). This 4P map is shown to be convertible to a three-site field map which provides equivalent performance, highlighting the viability of both field- and potential-based maps for amide I spectral modeling. The use of multiple sampling points for local electrostatics is found to be essential for accurate map performance. PMID- 26277121 TI - From molecular systems to continuum solids: A multiscale structure and dynamics. AB - We propose a concurrent multiscale molecular dynamics for molecular systems in order to apply macroscale mechanical boundary conditions such as traction and average displacement for solid state materials, which is difficult to do in traditional molecular dynamics where boundary conditions are applied in terms of forces and displacements on selected particles. The multiscale model is systematically constructed in terms of multiscale structures of kinematics, force field, and dynamical equations. The idea is to extend the Anderson-Parrinello Rahman molecular dynamics to the cases that have arbitrary finite domain and boundary, thus the model is capable of solving inhomogeneous, non-equilibrium problems. The macroscale stress loading on a representative volume element with periodic boundary condition is generalized to all kinds of macroscale mechanical boundary conditions. Unlike most multiscale techniques, our theory is aimed at understanding fundamental physics rather than achieving computing efficiency. Examples of problems with prescribed average displacements and surface tractions are presented to demonstrate the validity of the proposed multiscale molecular dynamics. PMID- 26277122 TI - Spin-orbit couplings within the equation-of-motion coupled-cluster framework: Theory, implementation, and benchmark calculations. AB - We present a formalism and an implementation for calculating spin-orbit couplings (SOCs) within the EOM-CCSD (equation-of-motion coupled-cluster with single and double substitutions) approach. The following variants of EOM-CCSD are considered: EOM-CCSD for excitation energies (EOM-EE-CCSD), EOM-CCSD with spin flip (EOM-SF-CCSD), EOM-CCSD for ionization potentials (EOM-IP-CCSD) and electron attachment (EOM-EA-CCSD). We employ a perturbative approach in which the SOCs are computed as matrix elements of the respective part of the Breit-Pauli Hamiltonian using zeroth-order non-relativistic wave functions. We follow the expectation value approach rather than the response-theory formulation for property calculations. Both the full two-electron treatment and the mean-field approximation (a partial account of the two-electron contributions) have been implemented and benchmarked using several small molecules containing elements up to the fourth row of the periodic table. The benchmark results show the excellent performance of the perturbative treatment and the mean-field approximation. When used with an appropriate basis set, the errors with respect to experiment are below 5% for the considered examples. The findings regarding basis-set requirements are in agreement with previous studies. The impact of different correlation treatment in zeroth-order wave functions is analyzed. Overall, the EOM-IP-CCSD, EOM-EA-CCSD, EOM-EE-CCSD, and EOM-SF-CCSD wave functions yield SOCs that agree well with each other (and with the experimental values when available). Using an EOM-CCSD approach that provides a more balanced description of the target states yields more accurate results. PMID- 26277123 TI - Positive semidefinite tensor factorizations of the two-electron integral matrix for low-scaling ab initio electronic structure. AB - Tensor factorization of the 2-electron integral matrix is a well-known technique for reducing the computational scaling of ab initio electronic structure methods toward that of Hartree-Fock and density functional theories. The simplest factorization that maintains the positive semidefinite character of the 2 electron integral matrix is the Cholesky factorization. In this paper, we introduce a family of positive semidefinite factorizations that generalize the Cholesky factorization. Using an implementation of the factorization within the parametric 2-RDM method [D. A. Mazziotti, Phys. Rev. Lett. 101, 253002 (2008)], we study several inorganic molecules, alkane chains, and potential energy curves and find that this generalized factorization retains the accuracy and size extensivity of the Cholesky factorization, even in the presence of multi reference correlation. The generalized family of positive semidefinite factorizations has potential applications to low-scaling ab initio electronic structure methods that treat electron correlation with a computational cost approaching that of the Hartree-Fock method or density functional theory. PMID- 26277124 TI - Aspects of the Eckart frame ro-vibrational kinetic energy operator. AB - A most decisive part of developing the Eckart frame ro-vibrational kinetic energy operator (KEO) in terms of curvilinear internal coordinates is the introduction of vibrational displacements obeying the Eckart conditions. It is examined here, how such displacements may be constructed by orthogonal and nonorthogonal transformations, and how they can be employed in developing the KEO. In particular, it is shown analytically, by term by term comparison, that the Eckart KEOs obtained by employing Pickett's method and the gateway Hamiltonian method are equivalent. That is, although it may appear in the form of very different expressions, the general, exact ro-vibrational Eckart frame KEO is unique. As side result, it has been shown that the simple formula of the pseudo-potential derived by Watson for the exact KEO given in normal coordinates applies to any Eckart frame KEO, irrespective of the choice of the vibrational coordinates. PMID- 26277125 TI - Spatiotemporal chaos from bursting dynamics. AB - In this paper, we study the emergence of spatiotemporal chaos from mixed-mode oscillations, by using an extended Oregonator model. We show that bursting dynamics consisting of fast/slow mixed mode oscillations along a single attractor can lead to spatiotemporal chaotic dynamics, although the spatially homogeneous solution is itself non-chaotic. This behavior is observed far from the Hopf bifurcation and takes the form of a spatiotemporal intermittency where the system locally alternates between the fast and the slow phases of the mixed mode oscillations. We expect this form of spatiotemporal chaos to be generic for models in which one or several slow variables are coupled to activator-inhibitor type of oscillators. PMID- 26277126 TI - Information processing in parallel through directionally resolved molecular polarization components in coherent multidimensional spectroscopy. AB - We propose that information processing can be implemented by measuring the directional components of the macroscopic polarization of an ensemble of molecules subject to a sequence of laser pulses. We describe the logic operation theoretically and demonstrate it by simulations. The measurement of integrated stimulated emission in different phase matching spatial directions provides a logic decomposition of a function that is the discrete analog of an integral transform. The logic operation is reversible and all the possible outputs are computed in parallel for all sets of possible multivalued inputs. The number of logic variables of the function is the number of laser pulses used in sequence. The logic function that is computed depends on the chosen chromophoric molecular complex and on its interactions with the solvent and on the two time intervals between the three pulses and the pulse strengths and polarizations. The outputs are the homodyne detected values of the polarization components that are measured in the allowed phase matching macroscopic directions, kl, kl=?iliki where ki is the propagation direction of the ith pulse and {li} is a set of integers that encodes the multivalued inputs. Parallelism is inherently implemented because all the partial polarizations that define the outputs are processed simultaneously. The outputs, which are read directly on the macroscopic level, can be multivalued because the high dynamical range of partial polarization measurements by nonlinear coherent spectroscopy allows for fine binning of the signals. The outputs are uniquely related to the inputs so that the logic is reversible. PMID- 26277127 TI - Quantum heat transport of a two-qubit system: Interplay between system-bath coherence and qubit-qubit coherence. AB - We consider a system consisting of two interacting qubits that are individually coupled to separate heat baths at different temperatures. The quantum effects in heat transport are investigated in a numerically rigorous manner with a hierarchial equations of motion (HEOM) approach for non-perturbative and non Markovian system-bath coupling cases under non-equilibrium steady-state conditions. For a weak interqubit interaction, the total system is regarded as two individually thermostatted systems, whereas for a strong interqubit interaction, the two-qubit system is regarded as a single system coupled to two baths. The roles of quantum coherence (or entanglement) between the two qubits (q q coherence) and between the qubit and bath (q-b coherence) are studied through the heat current calculated for various strengths of the system-bath coupling and interqubit coupling for high and low temperatures. The same current is also studied using the time convolutionless (TCL) Redfield equation and using an expression derived from the Fermi golden rule (FGR). We find that the HEOM results exhibit turnover behavior of the heat current as a function of the system bath coupling strength for all values of the interqubit coupling strength, while the results obtained with the TCL and FGR approaches do not exhibit such behavior, because they do not possess the capability of treating the q-b and q-q coherences. The maximum current is obtained in the case that the q-q coherence and q-b coherence are balanced in such a manner that coherence of the entire heat transport process is realized. We also find that the heat current does not follow Fourier's law when the temperature difference is very large, due to the non perturbative system-bath interactions. PMID- 26277128 TI - A novel Gaussian-Sinc mixed basis set for electronic structure calculations. AB - A Gaussian-Sinc basis set methodology is presented for the calculation of the electronic structure of atoms and molecules at the Hartree-Fock level of theory. This methodology has several advantages over previous methods. The all-electron electronic structure in a Gaussian-Sinc mixed basis spans both the "localized" and "delocalized" regions. A basis set for each region is combined to make a new basis methodology-a lattice of orthonormal sinc functions is used to represent the "delocalized" regions and the atom-centered Gaussian functions are used to represent the "localized" regions to any desired accuracy. For this mixed basis, all the Coulomb integrals are definable and can be computed in a dimensional separated methodology. Additionally, the Sinc basis is translationally invariant, which allows for the Coulomb singularity to be placed anywhere including on lattice sites. Finally, boundary conditions are always satisfied with this basis. To demonstrate the utility of this method, we calculated the ground state Hartree Fock energies for atoms up to neon, the diatomic systems H2, O2, and N2, and the multi-atom system benzene. Together, it is shown that the Gaussian-Sinc mixed basis set is a flexible and accurate method for solving the electronic structure of atomic and molecular species. PMID- 26277129 TI - A time domain two-particle approximation to calculate the absorption and circular dichroism line shapes of molecular aggregates. AB - The hierarchical equations of motion (HEOM) method has recently emerged as an effective approach to simulate linear and nonlinear spectroscopic signals of molecular aggregates in the intermediate coupling regime. However, its application to large systems is still limited when there are a large number of molecules in the molecular aggregate. In this work, we propose a time domain two particle approximation (TPA) in combination with the HEOM method to calculate the absorption and circular dichroism line shapes of molecular aggregates. The new method is shown to reduce the number of auxiliary density operators (ADOs) significantly for large systems, and a further truncation of the two-bath-set excited terms based on geometric considerations can lead to a linear increase of the number of ADOs with the system size. The validity of the HEOM-TPA method is first tested on one-dimensional model systems. The new method is then applied to calculate the absorption and circular dichroism line shapes of the Photosystem I core complex, as well as the population evolution of the Fenna-Matthews-Olson complex to demonstrate its effectiveness. PMID- 26277130 TI - Subspace formulation of time-dependent density functional theory for large-scale calculations. AB - A subspace formulation of time-dependent density functional theory (TDDFT) is proposed for large-scale calculations based on density functional perturbation theory. The formulation is implemented in conjunction with projector augmented wave method and plane-wave basis set. A key bottleneck of conventional TDDFT method is circumvented by projecting the time-dependent Kohn-Sham eigenvalue equations from a full Hilbert space to a substantially reduced sub-Hilbert space. As a result, both excitation energies and ionic forces can be calculated accurately within the reduced subspace. The method is validated for several model systems and exhibits the similar accuracy as the conventional TDDFT method but at a computational cost of the ground state calculation. The Born-Oppenheimer molecular dynamics can be successfully performed for excited states in C60 and T12 molecules, opening doors for many applications involving excited state dynamics. PMID- 26277131 TI - Derivative discontinuity with localized Hartree-Fock potential. AB - The localized Hartree-Fock potential has proven to be a computationally efficient alternative to the optimized effective potential, preserving the numerical accuracy of the latter and respecting the exact properties of being self interaction free and having the correct -1/r asymptotics. In this paper we extend the localized Hartree-Fock potential to fractional particle numbers and observe that it yields derivative discontinuities in the energy as required by the exact theory. The discontinuities are numerically close to those of the computationally more demanding Hartree-Fock method. Our potential enjoys a "direct-energy" property, whereby the energy of the system is given by the sum of the single particle eigenvalues multiplied by the corresponding occupation numbers. The discontinuities c? and c? of the spin-components of the potential at integer particle numbers N? and N? satisfy the condition c?N? + c?N? = 0. Thus, joining the family of effective potentials which support a derivative discontinuity, but being considerably easier to implement, the localized Hartree-Fock potential becomes a powerful tool in the broad area of applications in which the fundamental gap is an issue. PMID- 26277132 TI - Benchmark calculations on the nuclear quadrupole-coupling parameters for open shell molecules using non-relativistic and scalar-relativistic coupled-cluster methods. AB - Quantum-chemical computations of nuclear quadrupole-coupling parameters for 24 open-shell states of small molecules based on non-relativistic and spin-free exact two-component (SFX2C) relativistic equation-of-motion coupled-cluster (EOM CC) as well as spin-orbital-based restricted open-shell Hartree-Fock coupled cluster (ROHF-CC) methods are reported. Relativistic effects, the performance of the EOM-CC and ROHF-CC methods for treating electron correlation, as well as basis-set convergence have been carefully analyzed. Consideration of relativistic effects is necessary for accurate calculations on systems containing third-row (K Kr) and heavier elements, as expected, and the SFX2C approach is shown to be a useful cost-effective option here. Further, it is demonstrated that the EOM-CC methods constitute flexible and accurate alternatives to the ROHF-CC methods in the calculations of nuclear quadrupole-coupling parameters for open-shell states. PMID- 26277133 TI - A semiclassical treatment of the l-j correlation in atom-diatom collisions. AB - The explicit consideration of the vector correlations is an essential step when it comes to determining the mechanism of chemical reactions. Usual vector correlations involve initial and final relative velocity vectors and rotational angular momenta. However, the correlation between the orbital, l, and rotational, j, angular momenta has seldom received any attention. In this article, we present a semiclassical methodology capable of describing the l-j correlation that may serve as a connection between the quantum and quasiclassical treatments. Using the scattering matrix in the orbital angular momentum representation, the l-j correlation is expressed as a probability density function of the angle formed by both vectors. This technique is exemplified through the H + D2 reaction and its accuracy is appraised by comparing with results derived from calculations based on quasiclassical trajectories. PMID- 26277134 TI - A first-principles study on the B5O5 (+/0) and B5O5 (-) clusters: The boron oxide analogs of C6H5 (+/0) and CH3Cl. AB - The concept of boronyl (BO) and the BO/H isolobal analogy build an interesting structural link between boron oxide clusters and hydrocarbons. Based upon global minimum searches and first-principles electronic structural calculations, we present here the perfectly planar C2v B5O5 (+) (1, (1)A1), C2v B5O5 (2, (2)A1), and tetrahedral Cs B5O5 (-) (3, (1)A') clusters, which are the global minima of the systems. Structural and molecular orbital analyses indicate that C2v B5O5 (+) (1) [B3O3(BO)2 (+)] and C2v B5O5 (2) [B3O3(BO)2] feature an aromatic six-membered boroxol (B3O3) ring as the core with two equivalent boronyl terminals, similar to the recently reported boronyl boroxine D3h B6O6 [B3O3(BO)3]; whereas Cs B5O5 (-) (3) [B(BO)3(OBO)(-)] is characterized with a tetrahedral B(-) center, terminated with three BO groups and one OBO unit, similar to the previously predicted boronyl methane Td B5O4 (-) [B(BO)4 (-)]. Alternatively, the 1-3 clusters can be viewed as the boron oxide analogs of phenyl cation C6H5 (+), phenyl radical C6H5, and chloromethane CH3Cl, respectively. Chemical bonding analyses also reveal a dual three-center four-electron (3c-4e) pi hyperbond in Cs B5O5 (-) (3). The infrared absorption spectra of B5O5 (+) (1), B5O5 (2), and B5O5 (-) (3) and anion photoelectron spectrum of B5O5 (-) (3) are predicted to facilitate their forthcoming experimental characterizations. The present work completes the BnOn (+/0/-) series for n = 1-6 and enriches the analogous relationship between boron oxides and hydrocarbons. PMID- 26277135 TI - The geometrical change and intramolecular energy transfer upon S1<-S0 excitation in cyclopentanone. AB - The ultrafast dynamics in vibrationally hot S1 electronic excited state in cyclopentanone molecule was discovered with time resolved spectroscopy. Investigation of the geometry change upon the S1<-S0 excitation and D0<-S1 ionization has shown that the dihedral angle between the C=O bond and the plane given by the carbonyl and the alpha-carbons is 180 degrees either in S0 or D0 state and is reduced to 145.8 degrees by out-out-plane deformation of the oxygen in S1 state according to the theoretical calculation. The time domain experiments with femtosecond resolution have given rich insights into the energy transfer of the cyclopentanone molecule. The molecules are excited to the vibrationally hot S1 (n, pi(*)) state following absorption of one 267-nm photon. It is found that the population of the S1 (n, pi(*)) state undergoes ultrafast internal conversion to the highly vibrationally hot S0 state within 80 fs and nonradiative deactivation by intersystem crossing to triplet T1 (n, pi(*)) state occurring in 3.14 ps. Several Rydberg states have worked as stepping stones during the ionization. The available energy was distributed in the symmetric methylene group wagging and the symmetric skeletal ring breathing modes in D0 state. PMID- 26277136 TI - Photoelectron spectrum of PrO(-). AB - The photoelectron (PE) spectrum of PrO(-) exhibits a short 835 +/- 20 cm(-1) vibrational progression of doublets (210 +/- 30 cm(-1) splitting) assigned to transitions from the 4f(2) [(3)H4] sigma6s (2) Omega = 4 anion ground state to the 4f(2) [(3)H4] sigma6s Omega = 3.5 and 4.5 neutral states. This assignment is analogous to that of the recently reported PE spectrum of CeO(-), though the 82 cm(-1) splitting between the 4f [(2)F2.5] sigma6s Omega = 2 and Omega = 3 CeO neutral states could not be resolved [Ray et al., J. Chem. Phys. 142, 064305 (2015)]. The origin of the transition to the Omega = 3.5 neutral ground state is 0.96 +/- 0.01 eV, which is the adiabatic electron affinity of PrO. Density functional theory calculations on the anion and neutral molecules support the assignment. The appearance of multiple, irregularly spaced and low-intensity features observed ca. 1 eV above the ground state cannot be reconciled with low lying electronic states of PrO that are accessible via one-electron detachment. However, neutral states correlated with the 4f(2) [(3)H4] 5d superconfiguration are predicted to be approximately 1 eV above the 4f(2) [(3)H4] sigma6s Omega = 3.5 neutral ground state, leading to the assignment of these features to shake-up transitions to the excited neutral states. Based on tentative hot band transition assignments, the term energy of the previously unobserved 4f(2) [(3)H4] sigma6s Omega = 2.5 neutral state is determined to be 1840 +/- 110 cm(-1). PMID- 26277137 TI - Electron collisions with methyl-substituted ethylenes: Cross section measurements and calculations for 2-methyl-2-butene and 2,3-dimethyl-2-butene. AB - We report electron-scattering cross sections determined for 2-methyl-2-butene [(H3C)HC = C(CH3)2] and 2,3-dimethyl-2-butene [(H3C)2C = C(CH3)2] molecules. Absolute grand-total cross sections (TCSs) were measured for incident electron energies in the 0.5-300 eV range, using a linear electron-transmission technique. The experimental TCS energy dependences for the both targets appear to be very similar with respect to the shape. In each TCS curve, three features are discernible: the resonant-like structure located around 2.6-2.7 eV, the broad distinct enhancement peaking near 8.5 eV, and a weak hump in the vicinity of 24 eV. Theoretical integral elastic (ECS) and ionization (ICS) cross sections were computed up to 3 keV by means of the additivity rule (AR) approximation and the binary-encounter-Bethe method, respectively. Their sums, (ECS+ICS), are in a reasonable agreement with the respective measured TCSs. To examine the effect of methylation of hydrogen sides in the ethylene [H2C = CH2] molecule on the TCS, we compared the TCS energy curves for the sequence of methylated ethylenes: propene [H2C = CH(CH3)], 2-methylpropene [H2C = C(CH3)2], 2-methyl-2-butene [(H3C)HC = C(CH3)2], and 2,3-dimethyl-2-butene [(H3C)2C = C(CH3)2], measured in the same laboratory. Moreover, the isomeric effect is also discussed for the C5H10 and C6H12 compounds. PMID- 26277138 TI - Strong field coherent control of molecular torsions--Analytical models. AB - We introduce analytical models of torsional alignment by moderately intense laser pulses that are applicable to the limiting cases of the torsional barrier heights. Using these models, we explore in detail the role that the laser intensity and pulse duration play in coherent torsional dynamics, addressing both experimental and theoretical concerns. Our results suggest strategies for minimizing the risk of off-resonant ionization, noting the qualitative differences between the case of torsional alignment subject to a field-free torsional barrier and that of torsional alignment of a barrier-less system (equivalent to a 2D rigid rotor). We also investigate several interesting torsional phenomena, including the onset of impulsive alignment of torsions, field-driven oscillations in quantum number space, and the disappearance of an alignment upper bound observed for a rigid rotor in the impulsive torsional alignment limit. PMID- 26277139 TI - On the mechanism of Zn4O-acetate precursors ripening to ZnO: How dimerization is promoted by hydroxide incorporation. AB - We report on a combined experimental and molecular modelling study on Zn4O ion clusters stabilized by acetate molecules (OAc). In particular, ab initio calculations of acetate substitution by hydroxide ions are compared with mass spectrometry data. Though quantum calculations in the gas phase indicate strong energetic preference, no experimental evidence of stable Zn4O(OAc)6-x(OH)x clusters in ethanolic solutions could be observed. This apparent contradiction is rationalized by identifying the supportive role of hydroxide ions for the association of (OAc(-) -> OH(-) substituted) Zn4O(OAc)6 and Zn4O(OAc)5 (+) clusters. Mass spectrometry and quantum calculations hint at the stability of (Zn4O)2(OAc)12-x(OH)x dimers with x = 1, 2. Therein, the hydroxide ions establish salt-bridges that allow for the formation of additional Zn3 motifs with the OH above the triangle center-a structural motif close to that of the ZnO-crystal. The association of Zn4O(OAc)6 clusters is thus suggested to involve OAc(-) -> OH( ) substitution as an activation step, quickly followed by dimerization and the subsequent agglomeration of oligomers. PMID- 26277140 TI - Thermodynamic precursors, liquid-liquid transitions, dynamic and topological anomalies in densified liquid germania. AB - The thermodynamic, dynamic, structural, and rigidity properties of densified liquid germania (GeO2) have been investigated using classical molecular dynamics simulation. We construct from a thermodynamic framework an analytical equation of state for the liquid allowing the possible detection of thermodynamic precursors (extrema of the derivatives of the free energy), which usually indicate the possibility of a liquid-liquid transition. It is found that for the present germania system, such precursors and the possible underlying liquid-liquid transition are hidden by the slowing down of the dynamics with decreasing temperature. In this respect, germania behaves quite differently when compared to parent tetrahedral systems such as silica or water. We then detect a diffusivity anomaly (a maximum of diffusion with changing density/volume) that is strongly correlated with changes in coordinated species, and the softening of bond-bending (BB) topological constraints that decrease the liquid rigidity and enhance transport. The diffusivity anomaly is finally substantiated from a Rosenfeld-type scaling law linked to the pair correlation entropy, and to structural relaxation. PMID- 26277141 TI - Interactions between water and 1-butyl-1-methylpyrrolidinium ionic liquids. AB - We report experimental results on the diffusivity of water in two ionic liquids obtained using the pulsed-gradient spin-echo NMR method. Both ionic liquids have the same cation, 1-butyl-1-methylpyrrolidinium, but different trifluoromethyl containing anions. One has a strongly hydrophobic anion, bis(trifluoromethylsulfonyl)amide, while the second has a hydrophilic anion, trifluoromethylsulfonate. Transport of water in these ionic liquids is much faster than would be predicted from hydrodynamic laws, indicating that the neutral water molecules experience a very different friction than the anions and cations at the molecular level. Temperature-dependent viscosities, conductivities, and densities are reported as a function of water concentration to further analyze the properties of the ionic liquid-water mixtures. These results on the properties of water in ionic liquids should be of interest to researchers in diverse areas ranging from separations, solubilizing biomass and energy technologies. PMID- 26277142 TI - Mixing effects in the crystallization of supercooled quantum binary liquids. AB - By means of Raman spectroscopy of liquid microjets, we have investigated the crystallization process of supercooled quantum liquid mixtures composed of parahydrogen (pH2) or orthodeuterium (oD2) diluted with small amounts of neon. We show that the introduction of the Ne impurities affects the crystallization kinetics in terms of a significant reduction of the measured pH2 and oD2 crystal growth rates, similarly to what found in our previous work on supercooled pH2-oD2 liquid mixtures [Kuhnel et al., Phys. Rev. B 89, 180201(R) (2014)]. Our experimental results, in combination with path-integral simulations of the supercooled liquid mixtures, suggest in particular a correlation between the measured growth rates and the ratio of the effective particle sizes originating from quantum delocalization effects. We further show that the crystalline structure of the mixtures is also affected to a large extent by the presence of the Ne impurities, which likely initiate the freezing process through the formation of Ne-rich crystallites. PMID- 26277143 TI - Pressure-induced structural changes in NH4Br. AB - We report angle dispersive X-ray diffraction (XRD) measurements and Raman spectroscopy on NH4Br up to 70.0 GPa at room temperature. Three thermodynamically stable phases (phases II, IV, and V) are confirmed and a new possible phase (phase VI) of P21/m symmetry is proposed whose structure was established from Rietveld refinement of synchrotron XRD data for the first time. The phase sequence observed in NH4Br is in accordance with phase II -> IV -> V -> VI. Phase V transforms into phase VI at about 57.8 GPa with a huge volume reduction of 30%. Still, the intramolecular distances are analyzed to better understand the nature of structures. The H-H interactions become markedly more important as the N-Br distances are compacted, which is probably the reason of the kink of symmetric stretching band (nu1) at the transition pressure. PMID- 26277144 TI - Photodetachment, electron cooling, and recombination, in a series of neat aliphatic room temperature ionic liquids. AB - Transient absorption following photodetachment of a series of neat methyl-alkyl pyrrolidinium bis(trifluoromethylsulfonyl)amides at 6.20 eV was measured with sub picosecond time resolution in the visible and near-IR portions of the spectrum. This series spans the onset of structuring in the liquids in the form of polarity alternation. Excitation promotes the electron into a delocalized state with a very large reactive radius. Strong transient absorption is observed in the visible spectrum with a ~700 fs lifetime, and much weaker, long-lived absorption is observed in the near-IR spectrum. Absorption in the visible is shown to be consistent with the hole, and absorption in the near-IR is assigned to the free solvated electron. Yield of free electrons is estimated at ~4%, is insensitive to the size of the cation, and is determined in less than 1 ps. Solvation of free electrons depends strongly on the size of the cation and correlates well with the viscosity of the liquid. In addition to radiolytic stability of the aliphatic cations, ultrafast, efficient recombination of separated charge in NTf2 (-) based ionic liquids following photo-excitation near the band-gap may prevent subsequent reactive damage associated with anions. PMID- 26277145 TI - Homogeneous SPC/E water nucleation in large molecular dynamics simulations. AB - We perform direct large molecular dynamics simulations of homogeneous SPC/E water nucleation, using up to ~ 4 ? 10(6) molecules. Our large system sizes allow us to measure extremely low and accurate nucleation rates, down to ~ 10(19) cm(-3) s( 1), helping close the gap between experimentally measured rates ~ 10(17) cm(-3) s(-1). We are also able to precisely measure size distributions, sticking efficiencies, cluster temperatures, and cluster internal densities. We introduce a new functional form to implement the Yasuoka-Matsumoto nucleation rate measurement technique (threshold method). Comparison to nucleation models shows that classical nucleation theory over-estimates nucleation rates by a few orders of magnitude. The semi-phenomenological nucleation model does better, under predicting rates by at worst a factor of 24. Unlike what has been observed in Lennard-Jones simulations, post-critical clusters have temperatures consistent with the run average temperature. Also, we observe that post-critical clusters have densities very slightly higher, ~ 5%, than bulk liquid. We re-calibrate a Hale-type J vs. S scaling relation using both experimental and simulation data, finding remarkable consistency in over 30 orders of magnitude in the nucleation rate range and 180 K in the temperature range. PMID- 26277146 TI - Structural stability, vibrational, and bonding properties of potassium 1, 1' dinitroamino-5, 5'-bistetrazolate: An emerging green primary explosive. AB - Potassium 1,1'-dinitroamino-5,5'-bistetrazolate (K2DNABT) is a nitrogen rich (50.3% by weight, K2C2N12O4) green primary explosive with high performance characteristics, namely, velocity of detonation (D = 8.33 km/s), detonation pressure (P = 31.7 GPa), and fast initiating power to replace existing toxic primaries. In the present work, we report density functional theory (DFT) calculations on structural, equation of state, vibrational spectra, electronic structure, and absorption spectra of K2DNABT. We have discussed the influence of weak dispersive interactions on structural and vibrational properties through the DFT-D2 method. We find anisotropic compressibility behavior (b). Body composition (fat mass, lean body mass, bone mass) and bone mineral density examination were performed by densitometry. Serum concentrations of bone metabolism markers and adipokines were determined by immunoenzymatic methods. RESULTS: In underweight children we observed significantly lower fat mass (p<0.0001), lean mass (p<0.001), bone mineral content (p<0.01) and bone mineral density both the total body (p<0.01) as well as lumbar spine L2-L4 (p<0.05) compared with normal-weight children. In the group of underweight children, serum concentration of bone resorption marker (CTX) was significantly higher than in normal-weight children (2.006+/-0.649 vs. 1.624+/-0.492 ng/ml, p<0.05), with no differences in the concentrations of osteocalcin and sclerostin between studied groups. The ratio of adipokines (leptin/adiponectin) was approximately 2-fold lower in underweight than in normal-weight subjects. In underweight children we observed positive correlations between concentrations of sclerostin and bone turnover markers (OC, CTX) and between adiponectin and CTX. However, there was no correlation between fat mass and leptin concentration in this group of children. CONCLUSIONS: Low body weight in prepubertal period is related with an alteration in the adipokines profile and bone metabolism markers, resulting in a decrease in bone mineral density. PMID- 26277174 TI - [Assessment of rehabilitation progress in patients with cervical radicular pain syndrome after application of high intensity laser therapy - HILT and Saunders traction device]. AB - Osteoarthritis of the spine is a major global health problem, it is an epidemic of our times. It affects all parts of the spine, but the hardest to treat is its cervical region. The cervical spine is most mobile, delicate and sensitive to any load. It requires special care in conservative treatment. To date the selection of effective therapeutic approaches has been controversial. AIM: The aim of the study was to assess the progress of rehabilitation in patients with cervical radicular pain syndrome after using two different methods of treatment: HILT and spinal axial traction with the use of Saunders device. MATERIALS AND METHODS: The randomized study included 150 patients (81 women and 69 men, aged 24-67 years, mean age 45.5) divided into two groups of 75 patients each with characteristic symptoms of radicular pain. The measurement of the range of cervical spine movement of the cervical spine, visual analog scale for pain - VAS and a NDI questionnaire (Neck Disability Index - Polish version) - an indicator of functional disorders - were used to evaluate the effectiveness of the two different therapies. RESULTS: The results obtained by Saunders method remained significantly higher than those obtained when HILT laser therapy was used for most of the examined parameters. A thorough analysis of the results showed greater analgesic efficacy, improved global mobility and reduced functional impairment in patients treated with Saunders method. CONCLUSIONS: Both therapeutic methods manifest analgesic effect and a positive impact on the improvement of range of cervical spine movement in patients with radicular pain in this spine region. HILT laser therapy and Saunders traction device reduce neck disability index in the treated patients. PMID- 26277175 TI - [Internet addiction among graduates of general secondary schools in Cracow and its correlation with body mass index and other health problems]. AB - Studies find increasing trend among children, adolescents and young adults to spend excessive amounts of time surfing in the Internet. Another serious problem is the increasing proportion of young people who are overweight and obese. There are only few papers trying to correlate these two trends. AIM: The aims of the study were as follows: identification the extent of Internet addiction among students of Krakow's secondary schools and its correlation with BMI and other health problems. MATERIALS AND METHODS: Cross-sectional study among 200 pupils of randomly selected Krakow's high schools was conducted. Internet addiction was evaluated by using the Internet Addiction Test (IAT) by Kimberly Young. Each participant filled in an authors' questionnaire about his/her basic social and medical information. For each participant BMI was calculated. RESULTS: It was found that 7% of study group was addicted to the Internet (above 49 points in the IAT questionnaire). Internet addicts had higher BMI. The study revealed also several statistically significant relationships between the level of Internet addiction and the time spent online, BMI, back pain, headache. CONCLUSIONS: There is a modest percentage of people addicted to the Internet in the population of high school graduates, but these people often complain of back pain and headaches. BMI is higher among addicted youths. The time spent by high school graduates on online activity is far beyond the time devoted to physical activity. PMID- 26277176 TI - [Post-polio syndrome - a case report]. AB - Post-polio syndrome occurs 30-40 years after polio virus infection. The main symptoms of PPS are slowly progressive muscle limbs paresis with muscle atrophy, joints pain, paresthesia. In 90% of patients the main symptom is fatigue that leads to physical and mental activity deterioration. The cause of disease remains unknown. Probably it is an effect of motoneurons damage during acute virus polio infection, their overloading and degeneration of remaining ones. In this study we described a case of man who developed PPS 36 years after Heine-Medin disease. The main symptom was intensification of right limb paresis and muscle atrophy. In electromyography there were damage features of muscle clinically affected and unaffected. Changes in lifestyle made possible to continue occupational activity. PMID- 26277177 TI - High-grade surface osteosarcoma of the rib - a case report. AB - Surface osteosarcomas refers to tumors originating from the surface of bone primarily connected with the periosteum. Approximately 1- 2% of osteosarcomas are located in thoracic bones. These tumors are characterized by wide range of radiologic, morphologic and histologic presentation, mainly affects patients in the second and third decade of life and has very poor prognosis. According to the current WHO classification of OS one of this kind of tumor is highgrade surface osteosarcoma which accounts for 0,4% of all OS cases. PMID- 26277178 TI - [Vitex Agnus Castus in the treatment of hyperprolactinemia and menstrual disorders - a case report]. AB - We describe a patient with mild hyperprolactinemia and menstrual disorders (oligomenorrhea). She presented relative hypoestrogenism in laboratory tests. Magnetic resonans excluded the presence of pituitary adenoma. Because patient developed a bromocriptine intolerance, the Vitex Agnus Castus (VAC) extract has been introduced. The VAC therapy was effective, with symptoms relief and improvement of hormonal tests. The VAC medicines are indicated for the treatment of premenstrual syndrome (PMS), mastalgia, menstrual disorders and mild hyperprolactinemia. The mechanism of action is not fully understood, but it is related to dopaniergic activity of diterpenes and castacin in VAC. The randomized clinical trials revealed efficacy of VAC extract in the treatmet of hyperprolactinemia, menstrual disorders, PMS and mastalgia. Good tolerability, lack of serious side-effects and drug interactions are the advantages of the VAC preparations. PMID- 26277179 TI - [The use of psychotropic drugs during breast-feeding]. AB - Breast milk is the best source of nutrients and provides much better protection than immune modified milk. In the United States around 500 000 cases of mental disorders affecting pregnant women are diagnosed each year. It is estimated that approximately 1/3 of these women need psychotropic drugs in a period of breast feeding. Despite the serious consequences of depression and its well-known effect on a newborn, the women are still reluctant to begin pharmacological treatment. The fear of side effects unfortunately still plays an important role in making such a decision. It has been proved that all psychiatric drugs can transfer into breast milk, but their levels are very low or even negligible for the newborn. Most laboratory tests do not reveal an adequate sensitivity to detect these low concentrations. One have to remember that in case of any disturbing symptoms which may result from the use of these drugs, the only procedure is to discontinue breastfeeding immediately. The knowledge of these effects of particular groups of psychotropic drugs in breast-feeding mothers is essential for every practitioner. This knowledge should also be available not only to psychiatrists, but gynecologists and pediatricians as well. For this reason, it seems to be reasonable to summarize the results of previously published studies dealing with the topic. PMID- 26277180 TI - [Pro-health prevention in perimenopausal women with regard to estrogen treatment]. AB - According to the latest demographic forecast in Poland is observed the progressive aging of the population with growing population of perimenopausal women. This is a special time in woman's life, in which there are many metabolic changes, neurovegetative symptoms and mental changes. All of them are connected with decreased concentration of sex hormones. Very important in this period are health behaviors, including healthy lifestyle, regular exercises and proper diet. Highly effective in removing menopausal symptoms is hormone replacement therapy. It also prevents the effects of metabolic disorders. This therapy is primary prevention of cardiovascular diseases and osteoporosis, depression, Alzheimer's and Parkinson's disease and urogenital atrophy. It also has to delay the process of aging. Clinical studies of HERS, WHI and MWS caused extreme caution in the use of hormone replacement therapy and distrust for this therapy between doctors and their patients. It is therefore important to establish priorities for action and individualized therapy, depending on the indications and contraindications for its use. PMID- 26277181 TI - [Omentin - a newly-discovered adipocytokine in insulin resistance pathogenesis]. AB - Increased consumption of highly processed food and low level of physical activity are the main culprits of the obesity epidemic. Excessive visceral fat is an independent risk factor for insulin resistance. Pathogenesis of insulin resistance includes increased oxidation of free fatty acids and chronic inflammation. It seems that a recently discovered adipokine - omentin can play a role in the complex phenomenon of insulin resistance. Studies have shown that the concentrations of omentin are reduced in conditions associated with insulin resistance, such as obesity, polycystic ovary syndrome, type 2 diabetes and gestational diabetes amongst others. Available research also indicate a positive correlation between plasma adiponectin and omentin. Biological functions of omentin and its mechanism of action are not fully understood. It has been determined that omentin enhances insulin-stimulated glucose uptake in subcutaneous and visceral adipose tissue. However, this adipokine does not stimulate basal glucose transport. It has been shown that omentin increases phosphorylation of AMP-activated protein kinase, which indicates a potential role of omentin in energy homeostasis. PMID- 26277182 TI - [The endocannabinoid system role in the pathogenesis of obesity and depression]. AB - Excessive consumption and obesity do not always have to be strictly pathological. The adjustment of food intake as well as the pleasure of eating are the results of the circulation of neurotransmitters, hormones and glucocorticoids which have an ability to regulate the activity of many receptors connected with G protein, including endocannabinoid receptors. The key role of endocannabinoids in pathogenesis of obesity is their overproduction by adipose cells. Endocannabinoids (eCBs) affect CB1 receptors and increase hunger, willingness to intake food, decrease peristalsis and delay stomach emptying. In obese people increased levels of both central and peripheral endocannabinoids are observed. It may be connected with higher availability of endocannabinoid precursors to synthesis from adipose tissue and lipids. Raised concentration of eCBs in the body may be the consequence of their catabolism dysfunction. There is a positive correlation between amount the number of receptors in the peripheral tissues and obesity increase. It is thought that expression of CB1 receptors in mesolimbic system is connected with motivation to consume food in response to rewarding factor. The appetite increase after cannabinoids use is probably caused by rewarding action of the consumed food and it results from excessive dopaminergic transmission in award system. The pharmacological inhibition of endocannabinoids activity leads to weight loss, but may also have negative consequences such as decreased mood, reduced tolerance of pain, intensified anxiety, anhedonia, depressive symptoms, even suicidal thoughts. In post mortem examinations a decrease in CB1 receptor density in grey matter of glial cells in patients with major depression was identified. The pleiotropic and extensive activity of endocannabinoid system can influence a range of neurotransmitters thereby modulating the psychiatric life phenomena, simultaneously being involved in metabolism control and energetic system of human body. Hence it is a link between metabolic disorders and depression and anxiety disorders. Therefore, in obese people depressive comorbidity is higher and it significantly worsens prognosis and decreases life quality. PMID- 26277183 TI - In vitro prediction of human intestinal absorption and blood-brain barrier partitioning: development of a lipid analog for micellar liquid chromatography. AB - Over the past decades, several in vitro methods have been tested for their ability to predict either human intestinal absorption (HIA) or penetration across the blood-brain barrier (BBB) of drugs. Micellar liquid chromatography (MLC) has been a successful approach for retention time measurements of drugs to establish models together with other molecular descriptors. Thus far, MLC approaches have only made use of commercial surfactants such as sodium dodecyl sulfate (SDS) and polyoxyethylene (23) lauryl ether (Brij35), which are not representative for the phospholipids present in human membranes. Miltefosine, a phosphocholine-based lipid, is presented here as an alternative surfactant for MLC measurements. By using the obtained retention factors and several computed descriptors for a set of 48 compounds, two models were constructed: one for the prediction of HIA and another for the prediction of penetration across the BBB expressed as log BB. All data were correlated to experimental HIA and log BB values, and the performance of the models was evaluated. Log BB prediction performed better than HIA prediction, although HIA prediction was also improved a lot (from 0.5530 to 0.7175) compared to in silico predicted HIA values. PMID- 26277184 TI - The biocompatibility of carbon hydroxyapatite/beta-glucan composite for bone tissue engineering studied with Raman and FTIR spectroscopic imaging. AB - The spectroscopic approaches of FTIR imaging and Raman mapping were applied to the characterisation of a new carbon hydroxyapatite/beta-glucan composite developed for bone tissue engineering. The composite is an artificial bone material with an apatite-forming ability for the bone repair process. Rabbit bone samples were tested with an implanted bioactive material for a period of several months. Using spectroscopic and chemometric methods, we were able to determine the presence of amides and phosphates and the distribution of lipid-rich domains in the bone tissue, providing an assessment of the composite's bioactivity. Samples were also imaged in transmission using an infrared microscope combined with a focal plane array detector. CaF2 lenses were also used on the infrared microscope to improve spectral quality by reducing scattering artefacts, improving chemometric analysis. The presence of collagen and lipids at the bone/composite interface confirmed biocompatibility and demonstrate the suitability of FTIR microscopic imaging with lenses in studying these samples. It confirmed that the composite is a very good background for collagen growth and increases collagen maturity with the time of the bone growth process. The results indicate the bioactive and biocompatible properties of this composite and demonstrate how Raman and FTIR spectroscopic imaging have been used as an effective tool for tissue characterisation. PMID- 26277185 TI - Raman spectroscopy for screening and diagnosis of cervical cancer. AB - Cervical cancer is the fourth most common cancer in women worldwide and mainly affects younger women. The mortality associated with cervical cancer can be reduced if the disease is detected at the pre-cancer stage. Current best-practice methods include cytopathology, HPV testing, and histopathology, but these methods are limited in terms of subjectivity, cost, and time. There is an unmet clinical need for new methods to aid clinicians in the early detection of cervical pre cancer. These methods should be objective and rapid and require minimal sample preparation. Raman spectroscopy is a vibrational spectroscopic technique by which incident radiation is used to induce vibrations in the molecules of a sample and the scattered radiation may be used to characterise the sample in a rapid and non destructive manner. Raman spectroscopy is sensitive to subtle biochemical changes occurring at the molecular level, enabling spectral variations corresponding to disease onset to be detected. Over the past 15 years, there have been numerous reports revealing the potential of Raman spectroscopy together with multivariate statistical analysis for the detection of a variety of cancers. This paper discusses the recent advances and challenges for cervical-cancer screening and diagnosis and offers some perspectives for the future. PMID- 26277186 TI - A novel direct spray-from-tissue ionization method for mass spectrometric analysis of human brain tumors. AB - Real-time feedback about dissected tissue during the neurosurgical procedure is strongly requested. A novel direct ionization mass spectrometric method for identifying pathological differences in tissues is proposed. The method is based on simultaneous extraction of tissue lipids and electrospray ionization which allows mass spectrometric data to be obtained directly from soft tissues. The advantage of this method is the stable flow of solvent, which leads to stable time-dependent spectra. The tissues included necrotized tissues and tumor tissues in different combinations. Capability for direct analysis of samples of dissected tissues during the neurosurgical procedure is demonstrated. Data validation is conducted by compound identification using precise masses from the MS profile, MS/MS, and isotopic distribution structure analysis. The method can be upgraded and applied for real-time identification of tissues during surgery. This paper describes the technique and its application perspective. For these purposes, other methods were compared with the investigated one and the results were shown to be reproducible. Differences in lipid profiles were observed even in tissues from one patient where distinctions between different samples could be poor. The paper presents a proof of concept for the method to be applied in neurosurgery particularly and in tissue analysis generically. The paper also contains preliminary results proving the possibility of observing differences in mass spectra of different tumors. PMID- 26277187 TI - Fluorescence polarization immunoassay using IgY antibodies for detection of valnemulin in swine tissue. AB - Immunoglobulin Y (IgY) is derived from egg yolk and has been identified as a cheap and high-yield immunoreagent. The application of IgY in immunoassays for the detection of chemical contaminants in food samples has rarely been reported. In this work, we describe a rapid and sensitive fluorescence polarization immunoassay (FPIA) for valnemulin (VAL) using IgY which was produced using a previously prepared immunogen. Three fluorophore-labeled VAL tracers were synthesized and the sensitivity of the best tracer (VAL-DTAF) in the optimized FPIA with antibody IgY100 demonstrated an IC50 value of 12 ng mL(-1) in buffer. After evaluation of several extraction procedures, acidified acetonitrile was selected to extract VAL from swine tissue. The recoveries of VAL in spiked swine tissue at three levels (50, 100, and 200 MUg kg(-1)) were higher than 79% with coefficients of variation (CVs) lower than 12%. The limit of detection (LOD) of the FPIA in swine tissue was 26 MUg kg(-1) and was lower than the maximum residue limit (MRL) of VAL set by the European Union. The study showed that IgY could be a good substitute for IgG when developing a high-throughput assay for chemical residues. PMID- 26277189 TI - Radiation dosimetry using decreasing TL intensity in a few variety of silicate crystals. AB - This study shows that there are some ionic crystals which after irradiation with high gamma dose Dm and subsequent irradiation with low doses ranging up to 500Gy present a decreasing TL intensity as dose increases. This interesting feature can be used as a calibration curve in radiation dosimetry. Such behavior can be found in green quartz, three varieties of beryl and pink tourmaline. In all these silicate crystals it can be shown that irradiation with increasing gamma-dose there is a dose Dm for which the TL intensity is maximum. Of course, Dm varies depending on the crystal and irradiated crystal with the dose Dm is stable. If one of these crystals is taken and irradiated with doses from low values up to 400-500Gy, a curve of decreasing TL intensity is obtained; such a curve can be used as a calibration curve. PMID- 26277188 TI - Development of an aptasensor based on a fluorescent particles-modified aptamer for ochratoxin A detection. AB - The presented work reports a generic fluorescent aptasensing design employing carboxy-modified fluorescent particles as a signal-generating probe and magnetic particles as a solid separation support. Carboxy-modified fluorescent particles were used to modify the aptamer and act as a signal-generating probe. Magnetic beads were used as an immobilization surface to perform the function of a solid separation support. As a proof of concept, the assay was used to detect ochratoxin A (OTA). Fluorescent detection based on the displacement and competition format was performed, and the obtained results were compared. The competition-based assays were characterized with improved analytical characteristics as compared to those based on the displacement principle. The competitive fluorescent assays showed a high sensitivity where the detection limit and IC50 were 0.005 and 7.2 nM respectively. The aptasensing platform was finally demonstrated for the detection of OTA in a beer sample. However, this is a generic approach that can be very easily extended to other matrixes to determine OTA. Additionally, the proposed concept of fluorescent particles as a signal-generating probe in combination with magnetic particles can also be integrated to other fluorescent-based affinity assays. PMID- 26277190 TI - New Insights on Coffea miRNAs: Features and Evolutionary Conservation. AB - Small RNAs influence the gene expression at the post-transcriptional level by guiding messenger RNA (mRNA) cleavage, translational repression, and chromatin modifications. In addition to model plants, the microRNAs (miRNAs) have been identified in different crop species. In this work, we developed a specific pipeline to search for coffee miRNA homologs on expressed sequence tags (ESTs) and genome survey sequences (GSS) databases. As a result, 36 microRNAs were identified and a total of 616 and 362 potential targets for Coffea arabica and Coffea canephora, respectively. The evolutionary analyses of these molecules were performed by comparing the primary and secondary structures of precursors and mature miRNAs with their orthologs. Moreover, using a stem-loop RT-PCR assay, we evaluated the accumulation of mature miRNAs in genomes with different ploidy levels, detecting an increase in the miRNAs accumulation according to the ploidy raising. Finally, a 5' RACE (Rapid Amplification of cDNA Ends) assay was performed to verify the regulation of auxin responsive factor 8 (ARF8) by MIR167 in coffee plants. The great variety of target genes indicates the functional plasticity of these molecules and reinforces the importance of understanding the RNAi-dependent regulatory mechanisms. Our results expand the study of miRNAs and their target genes in this crop, providing new challenges to understand the biology of these species. PMID- 26277191 TI - Kinetics of Methane Production from Swine Manure and Buffalo Manure. AB - The degradation kinetics of swine and buffalo manure for methane production was investigated. Six kinetic models were employed to describe the corresponding experimental data. These models were evaluated by two statistical measurements, which were root mean square prediction error (RMSPE) and Akaike's information criterion (AIC). The results showed that the logistic and Fitzhugh models could predict the experimental data very well for the digestion of swine and buffalo manure, respectively. The predicted methane yield potential for swine and buffalo manure was 487.9 and 340.4 mL CH4/g volatile solid (VS), respectively, which was close to experimental values, when the digestion temperature was 36 +/- 1 degrees C in the biochemical methane potential assays. Besides, the rate constant revealed that swine manure had a much faster methane production rate than buffalo manure. PMID- 26277192 TI - Enhanced Anti-Tumor (Anti-Proliferation) Activity of Recombinant Human Interleukin-29 (IL-29) Mutants Using Site-Directed Mutagenesis Method. AB - Interferon (IFN)-lambda, also known as IL-28A, IL-28B, or IL-29, is a new type III IFN, which shares many functional characteristics with type I IFN (alpha/beta). Currently, IFN-alpha is used in the treatment of certain forms of cancer with severe adverse effects. Some researches had stated that IFN-lambdas induced a similar but restricted growth inhibition of tumor cells relative to IFN alpha; moreover, mutations of IFN-lambdas could strongly impact its biological properties. In this study, three hIL-29 mutants (K33R, R35K, and K33R/R35K) were generated by site-directed mutagenesis and efficiently expressed in Pichia pastoris GS115, which have considerable abilities to inhibit the growth of BEL 7402, HCT-8, and SGC-7901 tumor cells in vitro. The results showed that these mutants (K33R, R35K, and K33R/R35K) exhibited a significantly enhanced anti proliferation activity against these tumor cells, compared with native hIL-29 in vitro. Further assay in vitro indicated that superior to K33R and R35K, K33R/R35K had a significant increase in anti-tumor activity compared with IFN-alpha2b, which suggested that the K33R/R35K could make improvement for the effectiveness of native hIL-29 in clinic and could be used as a potentially powerful candidate for cancer immunotherapy. PMID- 26277193 TI - Corrigendum to: "Human health risk assessment of pharmaceuticals and personal care products in plant tissue due to biosolids and manure amendments, and wastewater irrigation" [Environ. Int. 75 (2015) 223-233]. PMID- 26277194 TI - Right Lower Quadrant Pain in a Young Female: Ultrasound Diagnosis of Rectus Abdominis Tear. AB - BACKGROUND: Right lower quadrant pain in young females presents a frequent diagnostic challenge for emergency physicians, with a broad differential and several important diagnoses. Using an "ultrasound first" imaging strategy can help decrease the use of computed tomography scans, with associated savings in radiation exposure, cost, and other resource use. CASE REPORT: We report a case of right lower quadrant pain in a young woman. After her initial history and physical examination, appendicitis was the leading differential. A bedside ultrasound was performed, leading to the uncommon diagnosis of rectus abdominis muscle tear. The sonographic findings of a muscle tear include increase in size, loss of linear, homogeneous architecture, and decreased echogenicity. Making this diagnosis at the bedside using ultrasound obviated the need for further imaging, avoiding unnecessary radiation exposure, and decreasing emergency department length of stay and overall cost, while leading to a tailored treatment plan. Why Should an Emergency Physician Be Aware of This? Rectus abdominis tear is a cause of right lower quadrant pain that may mimic appendicitis and should be considered in patients with this complaint. The ability to make this diagnosis with bedside ultrasound may assist in several important patient-oriented outcomes. PMID- 26277195 TI - The alpha- and beta-Adrenergic Antagonist Controversy with Sympathomimetic Agents. PMID- 26277196 TI - Re: Not Another Boring Lecture: Let's Be the Guide on the Side. PMID- 26277197 TI - Cutaneous Xanthoma. PMID- 26277198 TI - Tremendous Intrahepatic Cavity. PMID- 26277199 TI - Novel therapies for osteoporosis. AB - Since the identification of osteoporosis as a major health issue in aging populations and the subsequent development of the first treatment modalities for its management, considerable progress has been made in our understanding of the mechanisms controlling bone turnover and disease pathophysiology, thus enabling the pinpointing of new targets for intervention. This progress, along with advances in biotechnology, has rendered possible the development of ever more sophisticated treatments employing novel mechanisms of action. Denosumab, a monoclonal antibody against RANKL, approved for the treatment of postmenopausal and male osteoporosis, significantly and continuously increases bone mineral density (BMD) and maintains a low risk of vertebral, non-vertebral, and hip fractures for up to 8 years. Currently available combinations of estrogens with selective estrogen receptor modulators moderately increase BMD without causing the extra-skeletal adverse effects of each compound alone. The cathepsin K inhibitor odanacatib has recently been shown to decrease vertebral, non vertebral, and hip fracture rates and is nearing approval. Romosozumab, an anti sclerosin antibody, and abaloparatide, a PTH-related peptide analog, are at present in advanced stages of clinical evaluation, so far demonstrating efficaciousness together with a favorable safety profile. Several other agents are currently in earlier clinical and preclinical phases of development, including dickkopf-1 antagonists, activin A antagonists, beta-arrestin analogs, calcilytics, and Src tyrosine kinase inhibitors. PMID- 26277200 TI - Octanoylated ghrelin attenuates angiogenesis induced by oxLDL in human coronary artery endothelial cells via the GHSR1a-mediated NF-kappaB pathway. AB - OBJECTIVE: Low concentrations of oxidized low-density lipoprotein (oxLDL) promote the in vitro angiogenesis of endothelial cells and play an important role in plaque angiogenesis, which may cause plaque vulnerability and enhance the risk of intravascular thrombosis. The aim of this research was to investigate the effects of octanoylated ghrelin on oxLDL-induced angiogenesis and the underlying molecular mechanisms involved in this process. MATERIALS/METHODS: Human coronary artery endothelial cells (HCAECs) were incubated with 5 MUg/ml oxLDL and treated with various concentrations of octanoylated ghrelin (10(-9)-10(-6)M) with or without inhibitors for 24h. Cell proliferation, migration, and in vitro angiogenesis were analyzed by bromodeoxyuridine (BrdU) staining and BrdU enzyme linked immunosorbent assay (ELISA), transwell assay, and tube formation on Matrigel, respectively. NF-kappaB (nuclear factor kappaB) expression was determined by Western-blot analysis. RESULTS: Treatment with oxLDL at 5 MUg/ml enhanced the proliferation, migration and tube formation of HCAECs. In contrast, pretreatment with octanoylated ghrelin significantly attenuated in vitro angiogenesis in oxLDL-induced HCAECs. In addition, Western blot analysis indicated that NF-kappaB expression was increased after oxLDL treatment, and that this effect was significantly reversed by pretreatment with octanoylated ghrelin. However, the NF-kappaB inhibitor PDTC or the GHSR1a inhibitor [D-Lys3]-GHRP-6 abolished the effects of octanoylated ghrelin on the inhibition of angiogenesis and NF-kappaB p65 expression induced by oxLDL. CONCLUSIONS: These findings suggest that octanoylated ghrelin attenuates angiogenesis induced by oxLDL in HCAECs via the inhibition of GHSR1a-mediated NF-kappaB pathway. Furthermore, octanoylated ghrelin may promote the stability of vulnerable plaques by inhibiting plaque angiogenesis. PMID- 26277201 TI - Effects of age, sex, lactation and social dominance on faecal egg count patterns of gastrointestinal nematodes in farmed eland (Taurotragus oryx). AB - The eland is a large African antelope that can be bred in a temperate climate, under similar conditions and production systems as cattle. However, knowledge of parasites in farmed elands outside the area of their native habitat is still limited, and information concerning factors that influence these parasites is lacking. Therefore, faecal samples from an entire herd of elands, including calves and adult females and males, were examined monthly over a one year period. Almost 84% of the animals were found to be positive for gastrointestinal nematodes. Strongyle-type eggs were most frequently detected (prevalence 75%), followed by Capillaria sp., Nematodirus sp. and Trichuris sp. eggs. Following culturing eggs to infective larvae, Teladorsagia sp., Trichostrongylus sp., Nematodirus sp., Cooperia sp. and Oesophagostomum sp. were identified. Following necropsy of two calves that died during the study one abomasal nematode (Teladorsagia circumcincta), five small intestinal nematode species (Nematodirus helvetianus, N. spathiger, Cooperia oncophora, C. curticei and Capillaria bovis) and two large intestinal nematodes (Oesophagostomum venulosum and Trichuris ovis) were recovered. From these findings, it is evident that the eland harbours nematodes that are typical for domestic cattle and small ruminants. Morphological and morphometric analyses of recovered nematodes revealed that these parasites do not require any special morphological adaptation to establish infection in elands. The faecal output of strongyle-type and Nematodirus sp. eggs was seasonal, with the highest egg production taking place during spring and summer. Calves had higher faecal egg counts (for all the monitored nematode species) than adults did. Lactation in females was significantly (P<0.0001) associated with higher strongyle nematode egg shedding. Social dominance also affected faecal egg count patterns. The lower the hierarchical position among adults (regardless of sex), the higher the risk of nematode infection. This effect was evident for strongyles (P<0.0001) and Capillaria sp. nematodes (P=0.0065). The results of our study suggest that control measures applicable in domestic cattle and small ruminants might be similarly applicable for controlling gastrointestinal nematode infections in captive farmed elands. PMID- 26277202 TI - Infectious disease surveillance in animal movement networks: An approach based on the friendship paradox. AB - The network of animal movements among livestock premises is an important topological structure for the spread of infectious diseases. The central focus of this study was to analyze strategies for selecting premises based on the friendship paradox ("your friends have more friends than you do") - in which premises that neighbor randomly selected premises are sampled for surveillance or control - to determine whether these strategies are viable alternatives for the surveillance and control of diseases in scenarios with insufficient data on animal movement. To test the effectiveness of these strategies, we performed three sets of simulations. In the first set, we examined the risk of spreading an infectious disease using the cattle movement network of the state of Mato Grosso, Brazil. All tested strategies based on the friendship paradox have comparable performance to the hub control strategy (controlling premises that sold more animals) and superior performance to random sampling in terms of both reducing the risk of purchasing infected animals and the number of premises that need to be controlled. In the second and third sets of simulations, we observed that the friendship paradox strategies were more sensitive than the random sampling strategy to detect cases and disease, respectively. The survey of the entire animal movement network to identify animal premises with a key role in trade is not always possible, either because the data are insufficient or because informal trade is significant. If surveying the network is not possible, all approaches based on knowledge of the network become useless. As an alternative, knowing that there is a hidden movement network that follows rules inherent to all networks, such as the friendship paradox, can be used to our advantage. Strategies based on the friendship paradox do not assume knowledge of the animal movement network and therefore may be viable alternatives for the surveillance or control of infectious diseases in the absence of network information, thus optimizing the use of human and financial resources. PMID- 26277203 TI - Thyroid Nodules and Shear Wave Elastography: A New Tool in Thyroid Cancer Detection. AB - This study determines the performance of virtual touch imaging quantification (VTIQ), a non-invasive shear wave elastography method for measuring thyroid nodule (TN) stiffness, in distinguishing benign from malignant TNs. This prospective study evaluates 707 TNs in 676 patients with fine-needle aspiration biopsy (FNAB). Before FNAB, both conventional B-mode ultrasound and shear wave elastography were performed. Surgical resection was recommended for FNAB results that were not clearly benign. Surgical pathology confirmed 82 malignant TNs. The receiver operating curve identified a single cut-off of 3.54 m/s as the maximum shear wave velocity (SWV) for predicting thyroid cancer (TC). The sensitivity and specificity were 79.27% and 71.52%, respectively. Positive predictive value (PPV) was 26.75% and negative predictive value (NPV) was 96.34%. Compared with B-mode US features for predicting malignancy, SWV >=3.54 m/s has a higher sensitivity, specificity, PPV and NPV. TN stiffness measured by VTIQ-generated shear wave elastography is an independent predictor of TC. PMID- 26277205 TI - Trends in antimicrobial susceptibility among anaerobes in Gran Canaria: Analysis of 15-years data. PMID- 26277204 TI - Gene scanning and heart attack risk. AB - Coronary heart disease remains the leading cause of death in the Western World. The advent of microarray and next-generation sequencing technologies has generated multi-dimensional data sets, allowing for new pathophysiological insights into this complex disease. To date, genome-wide association studies (GWAS) have identified 152 associated loci and 320 candidate genes, contributing to the genetic risk of coronary artery disease (CAD) and acute myocardial infarction (AMI). The majority of single nucleotide polymorphisms (SNPs) mediate their risk by unknown mechanisms. A functional analysis based on Gene Ontology and KEGG pathways of candidate genes that are associated with CAD/AMI-SNPs showed the strongest evidence for genes regulating cholesterol metabolism. Additional clusters were significantly enriched for pathways, which play prominent roles during AMI and the development of atherosclerotic plaques in vascular tissue, including focal adhesion/extracellular matrix interaction, TGF-beta signaling, apoptosis, regulation of vascular smooth muscle contraction, angiogenesis, calcium ion binding, and transcription factors. A systems genetics approach, which incorporates genetic risk with gene expression data, metabolomic data, and protein biochemistry into genome-wide network studies, holds promise to elucidate the complex interplay between genetic risk and environmental factors for coronary artery disease. PMID- 26277206 TI - [In vitro activity of fosfomycin, alone or in combination, against clinical isolates of carbapenem resistant Pseudomonas aeruginosa]. AB - INTRODUCTION: The increase in microorganisms showing patterns of multi-drug resistance or even pan-drug resistance is of growing concern. Fosfomycin (FO) is well known to be active against a wide variety of microorganisms, including highly resistant strains of Pseudomonas aeruginosa (P. aeruginosa), and can also synergistically act with other molecules. METHODS: This study examines the in vitro activity shown by FO against 120 strains of carbapenem-resistant P. aeruginosa using an agar dilution and a gradient diffusion test. Possible synergistic effects of the combinations of FO/amikacin and FO/ciprofloxacin were also examined using E-test and time-kill techniques. RESULTS: According to the epidemiological cut-off value (ECOFF) issued by the European Committee on Antimicrobial Susceptibility Testing (EUCAST), our results indicate that over three-quarters of the strains tested would be susceptible to FO treatment, especially if combined with another antimicrobial. The FO/ciprofloxacin combination had a synergistic effect on 40% of the clinical isolates, while for FO/amikacin this effect was only observed in 12% of the isolates. CONCLUSION: The appearance of carbapenem-resistant P. aeruginosa strains requires the evaluation by combination therapy. This report suggests that the FO/ciprofloxacin combination can be useful, showing a synergistic effect in 40% of the isolates. PMID- 26277207 TI - Enteropathogens and antibiotics. AB - Infectious gastroenteritis remains a public health problem. The most severe cases are of bacterial origin. In Spain, Campylobacter and Salmonella are the most prevalent bacterial genus, while Yersinia and Shigella are much less frequent. Most cases are usually self-limiting and antibiotic therapy is not generally indicated, unless patients have risk factors for severe infection and shigellosis. Ciprofloxacin, third generation cephalosporins, azithromycin, ampicillin, cotrimoxazole and doxycycline are the most recommended drugs. The susceptibility pattern of the different bacteria determines the choice of the most appropriate treatment. The aim of this review is to analyse the current situation, developments, and evolution of resistance and multidrug resistance in these 4 enteric pathogens. PMID- 26277208 TI - A review of the fundamentals of polymer-modified asphalts: Asphalt/polymer interactions and principles of compatibility. AB - During the last decades, the number of vehicles per citizen as well as the traffic speed and load has dramatically increased. This sudden and somehow unplanned overloading has strongly shortened the life of pavements and increased its cost of maintenance and risks to users. In order to limit the deterioration of road networks, it is necessary to improve the quality and performance of pavements, which was achieved through the addition of a polymer to the bituminous binder. Since their introduction, polymer-modified asphalts have gained in importance during the second half of the twentieth century, and they now play a fundamental role in the field of road paving. With high-temperature and high shear mixing with asphalt, the polymer incorporates asphalt molecules, thereby forming a swallowed network that involves the entire binder and results in a significant improvement of the viscoelastic properties in comparison with those of the unmodified binder. Such a process encounters the well-known difficulties related to the poor solubility of polymers, which limits the number of macromolecules able to not only form such a structure but also maintain it during high-temperature storage in static conditions, which may be necessary before laying the binder. Therefore, polymer-modified asphalts have been the subject of numerous studies aimed to understand and optimize their structure and storage stability, which gradually attracted polymer scientists into this field that was initially explored by civil engineers. The analytical techniques of polymer science have been applied to polymer-modified asphalts, which resulted in a good understanding of their internal structure. Nevertheless, the complexity and variability of asphalt composition rendered it nearly impossible to generalize the results and univocally predict the properties of a given polymer/asphalt pair. The aim of this paper is to review these aspects of polymer-modified asphalts. Together with a brief description of the specification and techniques proposed to quantify the storage stability, state-of-the-art knowledge about the internal structure and morphology of polymer-modified asphalts is presented. Moreover, the chemical, physical, and processing solutions suggested in the scientific and patent literature to improve storage stability are extensively discussed, with particular attention to an emerging class of asphalt binders in which the technologies of polymer-modified asphalts and polymer nanocomposites are combined. These polymer-modified asphalt nanocomposites have been introduced less than ten years ago and still do not meet the requirements of industrial practice, but they may constitute a solution for both the performance and storage requirements. PMID- 26277209 TI - Patient-centered rapid reviews will drive local decision making: commentary on Hartling et al. PMID- 26277210 TI - Lateral Femoral Condyle Flap: An Alternative Source of Vascularized Bone From the Distal Femur. AB - PURPOSE: To elucidate the vascular anatomy of the superolateral geniculate artery (SLGA) and its supply to the periosteum of the lateral femoral condyle (LFC) and to provide guidelines for flap design and describe an illustrative case. METHODS: Thirty-one fresh cadaveric limbs were dissected. The vascular anatomy of the SLGA and its distal branches to skin, muscle, and periosteum were identified. Fluoroscopic images were taken during continuous perfusion of a radiopaque contrast dye into the SLGA. Intra-arterial injections of latex rubber were performed in 12 cadaver limbs. The vascular territory was traced from the SLGA to its distal branches, and surrounding soft tissues were dissected. RESULTS: The SLGA originated from the popliteal artery 4.9 +/- 1.2 cm (range, 2.8-7 cm) from the knee joint and its pedicle diameter was 1.8 +/- 0.5 mm (range, 1-3 mm). SGLA pedicle-specific fluoroscopic angiography demonstrated a dense filigree of vessels over the lateral distal femur. Arterial latex injections confirmed that the SLGA supplied the periosteum of the LFC and distal femur shaft. The proximal most extent of periosteal perfusion was 11.7 +/- 2.1 cm (range, 9.3-14.1 cm) from the knee joint. The average pedicle length of LFC osteoperiosteal flaps was 4.8 +/- 0.9 cm (range, 3.5-6.3 cm). CONCLUSIONS: The LFC flap consistently demonstrated almost 12 cm of femur length perfusion based on the SLGA pedicle. The anatomy of this flap enables chimeric designs combining soft tissue, bone, and cartilage. CLINICAL RELEVANCE: The vascularized LFC flap is an option for reconstruction of osseous defects of the upper extremity. PMID- 26277211 TI - The effects of ambient temperature on outpatient visits for varicella and herpes zoster in Shanghai, China: a time-series study. AB - BACKGROUND: The seasonality of varicella and herpes zoster has been widely observed, but there is limited evidence on their associations with ambient temperature. OBJECTIVE: The associations between ambient temperature and outpatient visits for varicella and herpes zoster were examined. METHODS: We collected daily outpatient visit data for varicella (N = 3520) and herpes zoster (N = 6614) from a major hospital in Shanghai, China, from 2008 to 2010. We adopted the generalized additive model in time-series analysis to investigate the short-term associations between temperature and outpatient visits for varicella and herpes zoster after controlling for seasonal trends, day of the week, and humidity. RESULTS: A 1 degrees C increase in daily mean temperature was associated with a 1.33% (95% confidence interval 0.93%-1.74%) decrease in outpatient visits for varicella whereas it was associated with a 2.18% (95% confidence interval 1.90%-2.46%) increase in outpatient visits for herpes zoster. LIMITATIONS: Only 1 hospital was included and we did not control for individual level risk factors. CONCLUSION: Our results demonstrated that temperature variation might be an important risk factor for varicella and herpes zoster in China. PMID- 26277212 TI - Cutaneous microemboli from hydrophilic polymer after endovascular procedures. AB - BACKGROUND: Multiple devices and coatings assist with endovascular insertion of sheaths, catheters, and guide wires. Hydrophilic polymer coatings, a common component of endovascular surgical devices, reportedly cause microvascular obstruction and embolization, with various sequelae in organs and soft tissue. OBJECTIVE: We sought to describe clinical and histopathologic features of cutaneous manifestations of hydrophilic polymer gel emboli. METHODS: We evaluated the clinical and histopathologic characteristics of 8 patients with cutaneous complications of hydrophilic polymer gel emboli who presented in May 2013 through February 2015. RESULTS: Sudden onset of lower extremity livedo racemosa, purpuric patches, or both, occurred hours to days after endovascular procedures involving the aorta. Histopathologic evaluation showed basophilic lamellated material, consistent with hydrophilic polymer gel emboli, within small dermal vessels. LIMITATIONS: This was a retrospective study with small sample size and not controlled for all similar procedures in this population. CONCLUSION: Hydrophilic polymer gel coatings in endovascular devices can embolize to skin and cause microvascular occlusion, presenting as livedo racemosa, purpura, or both. Given the number of patients observed over a short period, this phenomenon may be underappreciated. Hydrophilic polymer gel emboli should be considered in differential diagnosis of livedo racemosa and purpura after endovascular procedure. PMID- 26277213 TI - Why does parental language input style predict child language development? A twin study of gene-environment correlation. AB - There are well-established correlations between parental input style and child language development, which have typically been interpreted as evidence that the input style causes, or influences the rate of, changes in child language. We present evidence from a large twin study (TEDS; 8395 pairs for this report) that there are also likely to be both child-to-parent effects and shared genetic effects on parent and child. Self-reported parental language style at child age 3 and age 4 was aggregated into an 'informal language stimulation' factor and a 'corrective feedback' factor at each age; the former was positively correlated with child language concurrently and longitudinally at 3, 4, and 4.5 years, whereas the latter was weakly and negatively correlated. Both parental input factors were moderately heritable, as was child language. Longitudinal bivariate analysis showed that the correlation between the language stimulation factor and child language was significantly and moderately due to shared genes. There is some suggestive evidence from longitudinal phenotypic analysis that the prediction from parental language stimulation to child language includes both evocative and passive gene-environment correlation, with the latter playing a larger role. LEARNING OUTCOMES: The reader will understand why correlations between parental language and rate of child language are by themselves ambiguous, and how twin studies can clarify the relationship. The reader will also understand that, based on the present study, at least two aspects of parental language style - informal language stimulation and corrective feedback - have substantial genetic influence, and that for informal language stimulation, a substantial portion of the prediction to child language represents the effect of shared genes on both parent and child. It will also be appreciated that these basic research findings do not imply that parental language input style is unimportant or that interventions cannot be effective. PMID- 26277214 TI - Influence of dissolved organic carbon on the efficiency of P sequestration by a lanthanum modified clay. AB - A laboratory scale experiment was set up to test the effect of dissolved organic carbon (DOC) as well as ageing of the La-P complex formed during phosphorus (P) sequestration by a La modified clay (Phoslock((r))). Short term (7 days) P adsorption studies revealed a significant negative effect of added DOC on the P sequestration of Phoslock((r)), whereas a long-term P adsorption experiment revealed that the negative effect of added DOC was reduced with time. The reduced P binding efficiency is kinetic, as evident from solid-state (31)P magic-angle spinning (MAS) NMR spectroscopy, who showed that the P binding did not change in the presence of DOC. (31)P MAS NMR also reveals that up to 26% of the sequestered phosphate is as loosely bound redox-sensitive P species on the surface of rhabdophane (LaPO4 . nH2O, n <= 3). The ratio between the loosely bound P and lanthanum phosphate did not change with time, however both NMR and La LIII extended x-ray absorption fine structure (EXAFS) spectroscopy shows a transformation of lanthanum phosphate from the initially formed rhabdophane towards the more stable monazite (LaPO4). Furthermore, the effect of natural DOC on the P binding capacity was tested using water and pore water from 16 Danish lakes. Whilst DOC has an immediate negative impact on P binding in the lake water, with time this effect is reduced. PMID- 26277215 TI - Delimiting Species Boundaries within a Paraphyletic Species Complex: Insights from Morphological, Genetic, and Molecular Data on Paramecium sonneborni (Paramecium aurelia species complex, Ciliophora, Protozoa). AB - The demarcation of boundaries between protist species is often problematic because of the absence of a uniform species definition, the abundance of cryptic diversity, and the occurrence of convergent morphology. The ciliates belonging to the Paramecium aurelia complex, consisting of 15 species, are a good model for such systematic and evolutionary studies. One member of the complex is P. sonneborni, previously known only from one stand in Texas (USA), but recently found in two new sampling sites in Cyprus (creeks running to Salt Lake and Oroklini Lake near Larnaca). The studied Paramecium sonneborni strains (from the USA and Cyprus) reveal low viability in the F1 and F2 generations of interstrain hybrids and may be an example of ongoing allopatric speciation. Despite its molecular distinctiveness, we postulate that P. sonneborni should remain in the P. aurelia complex, making it a paraphyletic taxon. Morphological studies have revealed that some features of the nuclear apparatus of P. sonneborni correspond to the P. aurelia spp. complex, while others are similar to P. jenningsi and P. schewiakoffi. The observed discordance indicates rapid splitting of the P. aurelia-P. jenningsi-P. schewiakoffi group, in which genetic, morphological, and molecular boundaries between species are not congruent. PMID- 26277216 TI - CRISPR mediated somatic cell genome engineering in the chicken. AB - Gene-targeted knockout technologies are invaluable tools for understanding the functions of genes in vivo. CRISPR/Cas9 system of RNA-guided genome editing is revolutionizing genetics research in a wide spectrum of organisms. Here, we combined CRISPR with in vivo electroporation in the chicken embryo to efficiently target the transcription factor PAX7 in tissues of the developing embryo. This approach generated mosaic genetic mutations within a wild-type cellular background. This series of proof-of-principle experiments indicate that in vivo CRISPR-mediated cell genome engineering is an effective method to achieve gene loss-of-function in the tissues of the chicken embryo and it completes the growing genetic toolbox to study the molecular mechanisms regulating development in this important animal model. PMID- 26277217 TI - AP-2beta is a transcriptional regulator for determination of digit length in tetrapods. AB - The species-specific morphology of digits in the tetrapod limb, including the length and number of metacarpal, metatarsal, and phalangeal bones, suggests that a common developmental mechanism for digit formation is modified in a species specific manner. Here, we examined the function of the AP-2beta transcription factor in regulating digit length in the chicken autopod. Mutations in the gene encoding AP-2beta are associated with Char syndrome, a human autosomal dominant disorder. Char syndrome patients exhibit autopod skeletal defects, including loss of phalanges and shortened fingers, suggestive of a function for AP-2beta in normal digit development. The ectopic expression of two different dominant negative forms of chick AP-2beta, equivalent to mutant forms associated with human Char syndrome, in the developing chick hindlimb bud resulted in defective digit formation, including reductions in the number and length of phalanges and metatarsals. A detailed analysis of the AP-2beta expression pattern in the limb bud indicated a correlation between the pattern/duration of AP-2beta expression in the limb mesenchyme and digit length in three amniote species, the chicken, mouse and gecko. In addition, we found that AP-2beta expression was downstream of Fgf signals from the apical ectodermal ridge, which is crucial in digit morphogenesis, and that excessive AP-2beta function resulted in dysregulated digit length. Taken together, these results suggest that AP-2beta functions as a novel transcriptional regulator for digit morphogenesis. PMID- 26277219 TI - Cytotoxicity of gold nanoparticles in human neural precursor cells and rat cerebral cortex. AB - Nanoparticles are promising tools for the advancement of drug delivery, medical imaging, and as diagnostic sensor. Medical nanodevices should develop miniaturization, because it would be injected into a human body. Gold nanoparticles (GNPs) with different sizes and shapes have therapeutic potential as a result of their small size, robust nature, excellent biocompatibility and optical properties. However, the application of GNPs as medical nanodevices it is necessary to know the biodegradation, biocompatibility, and development of surface coating which avoid the accumulation of nanoparticles. In this study, we carry out an in vitro toxicity and in vivo gene expression study using two kinds of GNPs. We found that GNPs toxicity is dependent on the dose or size administrated after the injected GNPs into the brain, and small particle size GNPs appeared more nestin expression compared to large particle size at short term implantation. These findings of toxicity of GNPs may play an important role in development of in vivo tools for the safety of GNPs. PMID- 26277218 TI - Is radiofrequency ablation applicable for recurrent hepatocellular carcinoma after liver transplantation? AB - BACKGROUND: Radiofrequency ablation (RFA) is a radical treatment for both primary and recurrent small hepatocellular carcinoma (HCC) with an optimistic outcome which is comparable with surgery. For localized recurrence of HCC after liver transplantation (LTx), surgical resection is considered the most favorable treatment. When surgical resection is contraindicated or technically infeasible, whether RFA is as efficient after transplantation as in nontransplant settings remains unclear. MATERIALS AND METHODS: A cohort study was undertaken in a population of patients that had a recurrence of HCC after LTx to evaluate the outcomes of different modalities (surgery, RFA, and conservative therapy) on long term survival. RESULTS: Seventy-eight of the 486 HCC patients who received LTx had a recurrence (16%). Fifteen patients underwent surgical resection, and 11 patients were treated with RFA. The remaining 52 patients received conservative therapy (17 patients with sirolimus plus sorafenib regimen; the others were treated with conventional supportive therapy). The 1-, 3-, and 5-y overall survival rates were 92%, 51%, and 35% for the patients treated with surgery and 87%, 51%, and 28% for the patients that received RFA. The corresponding 1-, 3-, and 5-y rerecurrence-free survival rates were 83%, 16%, and 16% for the patients treated with surgery and 76%, 22%, and 0% for the patients that received RFA, respectively. There was no significant difference in overall survival or rerecurrence-free survival between the surgical resection group and the RFA group (P = 0.879, P = 0.745). CONCLUSIONS: For HCC recurrence after LTx, RFA is preferable when surgical resection is contraindicated or technically infeasible and provides comparable long-term survival compared with surgery. PMID- 26277220 TI - Investigating the role of co-substrate-substrate ratio and filter media on the performance of anammox hybrid reactor treating nitrogen rich wastewater. AB - This study explored the feasibility of using the anammox hybrid reactor (AHR), which combines suspended and attached growth media, for the biodegradation of ammonical nitrogen in wastewater. The study was performed in four laboratory scale AHRs, inoculated with mixed seed culture (1:1). The anammox process was established by feeding the AHR with synthetic wastewater, containing NH(4)-N and NO(2)-N (1:1), at hydraulic retention time (HRT) of 1 day. The reactors were gradually acclimated to a higher ammonium concentration (1200 mg/l) until the pseudo-steady state was attained. Subsequently, the reactors were operated at various HRTs (0.25-3.0 days) to optimize the HRT and nitrogen loading rate (NLR). The study demonstrated that HRT of 1 day, corresponding to 95.1% of nitrogen removal was optimal. Pearson correlation analysis indicated the strong and positive correlation of HRT and sludge retention time (SRT), whereas the NLR and biomass yield correlated negatively with the nitrogen removal efficiency (NRE). The mass balance of nitrogen showed that a major fraction (79.1%) of the input nitrogen was converted into N2 gas, and 11.25% was utilized in synthesizing the biomass. The filter media in the AHR contributed to an additional 15.4% of ammonium removal and a reduction of 29% in the sludge washout rate. The nitrogen removal kinetics in the AHR followed the modified Stover-Kincannon model, whereas the Lawrence-McCarty model best described the bacterial growth kinetics. The study concludes that the hybrid configuration of the reactor demonstrated promising results and could be suitably applied for industrial applications. PMID- 26277221 TI - Increasing Timely Postpartum Oral Glucose Tolerance Test Completion in Women with Gestational Diabetes: A Quality-Improvement Initiative. PMID- 26277222 TI - Contextualizing the Proven Effectiveness of a Lifestyle Intervention for Type 2 Diabetes in Primary Care: A Qualitative Assessment Based on the RE-AIM Framework. AB - OBJECTIVE: The Healthy Eating and Active Living for Diabetes in Primary Care Networks (HEALD) intervention proved effective in increasing daily physical activity among people with type 2 diabetes in 4 community-based primary care networks (PCNs) in Alberta. Here, we contextualize its effectiveness by describing implementation fidelity and PCN staff's perceptions of its success in improving diabetes management. METHODS: We used the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework to evaluate the HEALD intervention. Qualitative methods used to collect data related to the RE-AIM dimensions of implementation and effectiveness included interviews with PCN staff (n=24), research team reflections (n=4) and systematic documentation. We used content analysis, and data were imported into and managed using Nvivo 10. RESULTS: HEALD was implemented as intended with adequate fidelity across all 4 PCNs. Identified implementation facilitators included appropriate human resources, the training provided, ongoing support, the provision of space and the simplicity of the intervention. However, PCN staff reported varying opinions regarding its potential for improving diabetes management among patients. Rationales for their views included intervention "dose" inadequacy; that the quality of usual care for people with diabetes was already good; patients were already managing their diabetes well; and the potential for cointervention. Recommended improvements to HEALD included increasing the dose of the intervention, expanding it to other modes of exercise and incorporating a medical clearance process. CONCLUSIONS: Based on the high degree of fidelity, the demonstrated effectiveness of HEALD in improving physical activity among patients was a result of sound implementation of an efficacious intervention. Increasing the dose of HEALD could result in additional improvements for patients. PMID- 26277223 TI - Association between Alcohol Consumption and Glycemic Status in Middle-Aged Women. AB - OBJECTIVES: Habitual alcohol drinking has been shown to reduce the risk for diabetes by recent meta-analysis studies. However, it remains to be clarified whether the relationship between alcohol and diabetes is influenced by adiposity. The purpose of this study was to determine whether glycemic status is influenced by alcohol drinking in women. METHODS: The subjects were 18 352 Japanese women, 35 to 60 years of age, who underwent health check-up examinations. The subjects were divided into 4 groups: nondrinkers, occasional drinkers, regular light drinkers (<22 g ethanol/day) and regular heavy drinkers (>=22 g ethanol/day). The relationship between alcohol consumption and glycated hemoglobin (A1C) levels was investigated by using analysis of covariance and logistic regression analysis with adjustment for age and histories of smoking and regular exercise. RESULTS: A1C levels were significantly lower in occasional, regular light and regular heavy drinkers than in nondrinkers and was significantly lower in regular light and heavy drinkers than in occasional drinkers. These inverse associations were not altered by adiposity status as evaluated by body mass index and waist-to height ratios. Odds ratios versus nondrinkers for hyperglycemia were significantly lower (p<0.01) than the reference level of 1.00 in occasional drinkers (0.82 [95% confidence interval 0.73 to 0.92]); regular light drinkers (0.61 [95% CI: 0.44 to 0.85]) and regular heavy drinkers (0.66 [95% CI: 0.50 to 0.88]). CONCLUSIONS: The results suggest that glycemic status is inversely associated with alcohol drinking independent of adiposity status in Japanese women. This may be related to the known lower risk for cardiovascular disease in female drinkers. PMID- 26277224 TI - Feasibility and effectiveness of the Integrated Psychological Therapy (IPT) in patients with schizophrenia: a preliminary investigation from India. AB - Functional outcome is an important index of recovery in patients with Schizophrenia (SZ). Several factors impact social functioning, including neurocognition. The Integrated Psychological Therapy (IPT) has been effective in improving social-functioning in SZ patients, but needs to be evaluated for its feasibility and impact in the Indian subcontinent. The study examined the effectiveness of the IPT on neurocognition and social functioning in patients with SZ. An open label design with baseline, post-intervention and 3-month follow up assessments was adopted. Twenty nine clinically stable out-patients with schizophrenia/schizo-affective disorder (DSM IV-TR) providing written informed consent were recruited, of whom 23 completed the intervention. Patients were assessed on tests of neurocognition, social functioning and symptomatology. Following baseline assessment, patients received 16-20, 1h individual sessions of the IPT over 2.5-3 months. The structure and content of the IPT was modified to make it culturally appropriate for the Indian subcontinent. Therapy comprised of psycho education and the first four modules of the IPT. Repeated measures analysis of variance (RMANOVA) for the completers sample (N=23) indicated significant improvement in social-functioning, symptom severity and certain domains of neurocognition following the intervention. Large effect sizes of 1.21 and 1.01 were obtained for scores on Social and Occupational Functioning Scale (SOFS) and Groningen Social Disabilities Schedule (GSDS) respectively at 3-month follow-up. The IPT was effective in improving social-functioning and neurocognition in Indian patients with SZ. The study demonstrated the durability of these improvements. PMID- 26277225 TI - The airplane crash in the French Alps: A preventable tragedy. PMID- 26277226 TI - Serotonin and interleukin-6: Association with pruritus severity, sleep quality and depression severity in Prurigo Nodularis. AB - Prurigo Nodularis (PN) is a chronic skin condition of unknown etiology. It is said to be associated with psychological factors. However, studies to identify the same are few. Hence, we undertook to assess the association between quality of sleep, depression, pruritus severity in cases of PN and to assess association of serum serotonin, interleukin (IL)-6 with sleep, depression and pruritus severity. This cross-sectional study involves 39 patients with PN and 39 age and gender matched healthy controls. Subjective quality of sleep, depressive symptom severity and pruritus severity were collected through clinician based interview. Serum serotonin and serum IL-6 were estimated by ELISA. Spearman correlation was used to assess the strength of association between biochemical parameters and clinical parameters. Cases had significantly higher percentage of depression, a higher score of depression severity, higher serum IL-6 level and lower serum serotonin levels. Serum serotonin and serum IL-6 showed significant correlation with the severity of pruritus (r=-0.66, p<0.01 and r=0.60, p<0.01). However, both these parameters showed a significantly negative correlation between them (r= 0.92, p<0.01). Though cause and effect cannot be established in this type of study, there is a disturbance of the inflammatory-neuroendocrine axis (interleukins-serotonin). PN is characterized by higher IL-6 and lower serotonin and greater depression severity than healthy controls. Findings of this study may have an influence on the treatment of PN. PMID- 26277227 TI - Improved immune responses to a bivalent vaccine of Newcastle disease and avian influenza in chickens by ginseng stem-leaf saponins. AB - Our previous investigation demonstrated that ginseng stem-leaf saponins (GSLS) derived from the stems and leaves of Panax ginseng C.A. Meyer promoted humoral and gut mucosal immunity in chickens vaccinated with live infectious bursa disease vaccine. The present study was designed to evaluate the effect of GSLS on the immune response to a bivalent inactive vaccine of Newcastle disease (ND) and avian influenza (AI) in chickens immunosuppressed by cyclophosphamide (Cy). One hundred and sixty-eight specific-pathogen-free (SPF) chickens were randomly divided into 7 groups, each containing 24 birds. Chickens in groups 3-7 received intramuscular injection of Cy at 100mg/kg BW for 3 days to induce immunosuppression. Groups 1 and 2 were injected with saline solution in the same way as groups 3-7. Following injection of Cy, groups 4-7 were orally administrated GSLS (2.5, 5 and 10mg/kg BW) or astragalus polysaccharide (APS) (200mg/L) in drinking water for 7 days; groups 1-3 were not medicated and served as control birds. After administration of GSLS or APS, groups 2-7 were subcutaneously injected with a bivalent inactive vaccine of ND and AI. After that, serum was sampled for detecting antibody titers by HI, spleen was collected for lymphocyte proliferation assay, and duodenum tissues were collected for measurement of IgA-secreting (IgA+) cells and intestinal intraepithelial lymphocytes (iIELs). The results showed that injection of Cy significantly suppressed immunity in chickens; oral administration of GSLS before immunization recovered splenocyte proliferation induced by ConA and LPS, and the numbers of IgA+ cells and iIELs as well as the specific antibody response to a bivalent inactive vaccine of ND and AIin immunosuppressed chickens treated with Cy. Therefore, GSLS may be the potential agent to improve vaccination in immunosuppressed chickens. PMID- 26277228 TI - Millennium Development Goals 4 and 5: Past and future progress. AB - We review global and regional progress towards Millennium Development Goals (MDGs) 4 and 5 with respect to their indicators, drawing on the latest data available from the relevant United Nations inter-agency groups responsible for maternal and child mortality estimation, as well as recent reports from individual UN agencies and external monitoring groups reporting on MDG progress. We also draw on recent, comprehensive evidence syntheses to present an overview of a selection of existing effective interventions that, if collectively implemented at scale, would reduce maternal and child deaths well beyond the MDG target levels. We conclude with a summary of why and how a focus on maternal and child health in the post-2015 era should be maintained, as the global development agenda transitions from the MDGs to the Sustainable Development Goals. PMID- 26277229 TI - Low-frequency oscillations in cerebrovascular and cardiovascular hemodynamics: Their interrelationships and the effect of age. AB - The aim of this study was to investigate how the interrelationships between low frequency oscillations (LFOs) in the cerebral and systemic cardiovascular hemodynamic systems change with aging and systemic hemodynamic perturbation. Seventeen young adult (28.4+/-3.5years) and seventeen elderly subjects (69.4+/ 8.7years) underwent continuous measurements of arterial blood pressure (ABP), heart rate (HR), and cerebral oxygenation (oxy-hemoglobin, deoxy-hemoglobin, and total hemoglobin) using near-infrared spectroscopy. The LFOs were subdivided into three frequency intervals (FI-1: 0.01-0.02Hz, FI-2: 0.02-0.06Hz, and FI-3: 0.06 0.15Hz) via spectral analysis based on continuous wavelet transform. The amplitudes of the LFOs at these FIs were calculated to examine the effects of aging and head-up tilt (HUT) on cerebral and cardiovascular hemodynamics. Granger causality (GC) was used for analyzing the causal relationships between the LFOs observed in ABP, oxy-hemoglobin, and HR. The amplitudes of the LFOs were generally higher in young adults than in the elderly and increased significantly only in the younger subjects after HUT. GCs in FI-3 oscillations were significantly higher in young subjects compared to older participants in the HUT state. These results indicate that aging dampens systemic and cerebral hemodynamic regulatory mechanisms, and the interrelationships between systemic and cerebral hemodynamics become weaker with age. PMID- 26277230 TI - 3-D reconstruction and multiple marker analysis of mouse proepicardial endothelial cell population. AB - BACKGROUND: The proepicardium (PE), a transient embryonic structure crucial for the development of the epicardium and heart, contains its own population of endothelial cells (ECs). The aim of our study was to determine the pattern, anatomical orientation and phenotypic marker expression of the endothelial cell network within the PE. RESULTS: Immunohistochemical findings revealed that proepicardial ECs express both early and late EC-specific markers such as CD31, Flk-1, Lyve-1 and Tie-2 but not SCL/Tal1, vWF, Dll4 or Notch1. Proepicardial ECs are present in the vicinity of the sinus venosus (SV) and form a continuous network of vascular sprouts/tubules connected with the SV endothelium, with Ter 119-positive erythroblasts in the vascular lumina. CONCLUSIONS: On the basis of our results, we postulate the existence of a continuous network of ECs in the PE, exhibiting connection and/or patency with the SV and forming vessels/tubules/strands. Marker expression suggests that ECs are immature and undifferentiated, which was also confirmed with a transmission electron microscopy (TEM) analysis. Our results deliver new data for a better understanding of the nature of proepicardial ECs. PMID- 26277231 TI - Does the incidence of sore throat postoperatively increase with the use of a traditional intubation blade or the GlideScope? AB - STUDY OBJECTIVE: The GlideScope video-guided laryngoscope is an alternative standard of care for rescue laryngoscopies when direct laryngoscopy is unsuccessful. During postoperative checks by an anesthesiologist, it was noticed that patients who reported sore throat often required GlideScope laryngoscopy. Consequently, it is difficult to determine whether postoperative sore throats are caused by irritation inflicted by multiple laryngoscopic attempts or the actual utilization of the GlideScope itself. The goal of this study was to determine whether the use of the GlideScope leads to a greater or lesser incidence of sore throat when compared with traditional laryngoscope blades used for intubation. DESIGN: Eligible patients scheduled for elective inpatient surgeries requiring endotracheal tube intubation were enrolled into this single-blinded prospective cohort study. chi(2) Test, Fisher exact test, and t tests were used to compare differences across the primary end point and other demographic categories. SETTING: Operating rooms and postanesthesia recovery unit, Albany Medical Center, Albany, NY. PATIENTS: There were a total of 151 patients with American Society of Anesthesiologists grades 1 to 3 included in the study. INTERVENTIONS: Eighty-one patients were randomized to a control group that received traditional laryngoscopy via Macintosh/Miller blades and 70 patients received video-guided intubation via the GlideScope. MEASUREMENTS: The incidence of postoperative sore throat was recorded via a yes/no questionnaire within 24 hours after extubation. Secondary parameters such as provider type, sex, and perceived difficulty were also recorded. MAIN RESULTS: There was no significant difference in the proportion of patients reporting sore throat by type of blade used (Mac/Miller 36.3% vs GlideScope 32.4%, P = .619). For secondary outcomes, women were significantly more likely to report sore throat as compared with men (men 24.3% vs women 43.2%, P = .015), and the provider type was significantly associated with the occurrence of postoperative sore throat (attendings 26.8% vs certified registered nurse anesthetists 52.3% vs third-year clinical anesthesia residents 30%, P = .012). CONCLUSIONS: Use of the GlideScope videolaryngoscopy was not significantly associated with increased occurrence of postoperative sore throat when compared with traditional intubation techniques. Our results may enable more trainees to acquire intubation skills with the GlideScope during an initial intubation attempt in patients with American Society of Anesthesiologist grades 1 to 3, with optimization of patient satisfaction in respect to postoperative sore throats. In addition, a provider's choice of intubation technique based on either Macintosh/Miller blades or the GlideScope does not significantly impact a patient's risk of postoperative sore throat. PMID- 26277232 TI - Where are we heading to in pharmacological IBD therapy? AB - After a relatively long time of failed developments and negative clinical trials in pharmacological inflammatory bowel disease (IBD) therapy we now phase a time of a great number of successful studies and new therapy principles that will most likely make it into clinical practice. This will change the landscape of IBD therapy in future markedly. Many new therapeutic principles have been developed and old ones that seemed to have failed such as anti-sense technology suddenly now provide promising results. Some initially promising therapies will need further development or have failed such as Trichuris suis ova therapy (but not helminth therapy in general), CCR9 targeted therapies or recombinant IL-10. In contrast anti-leukocate trafficking therapies appear to be quite promising. Vedolizumab is the first in class anti-integrin antibody that was approved for the therapy of CD and UC recently. Other anti-integrin antibodies and small molecule adhesion inhibitors will most likely be approved in the next years for IBD therapy. Tofacitinib, a small molecule JAK inhibitor, is a promising candidate for the treatment of UC. Phosphatidylcholine may be a future option for patients with 5-ASA refractory UC or 5-ASA intolerance. The preliminary data for Mongersen, a Smad7 antisense oligonucleotide, are promising despite some concerns about long term effect of TGFbeta induction. Anti IL6 strategies will hopefully be further evaluated keeping in mind the caveat of a lack of CRP induction in anti-IL6 treated patients. Stem cell transplantation will become an option for patients that have experienced failure of established medications. Fecal microbiota transplantation and also perhaps combined probiotic therapy is a field that will be evaluated in more detail in the near future especially for UC patients. Based on these new developments treatment algorithms need to be updated. This review will reflect these current developments and give a perspective for future IBD therapy. PMID- 26277233 TI - Time-Resolved Magnetic Resonance Angiography in the Evaluation of Intracranial Vascular Lesions and Tumors: A Pictorial Essay of Our Experience. AB - Time-resolved magnetic resonance angiography (TR MRA) is a promising less invasive technique for the diagnosis of intracranial vascular lesions and hypervascular tumors. Similar to 4-dimensional computed tomographic angiography obtaining high frame rate images, TR MRA utilizes acceleration techniques to acquire sequential arterial and venous phase images for identifying, localizing, and classifying vascular lesions. Because of the good agreement with digital subtraction angiography for grading brain arteriovenous malformations with the Spetzler-Martin classification and the good sensitivity for visualizing arteriovenous fistulas, studies have suggested that TR MRA could serve as a screening or routine follow-up tool for diagnosing intracranial vascular disorders. In this pictorial essay, we report on the use of TR MRA at 3.0 T to diagnose intracranial vascular lesions and hypervascular tumors, employing DSA as the reference technique. PMID- 26277234 TI - Positron Emission Tomography Computed Tomography: A Guide for the General Radiologist. AB - Cancer remains a leading cause of death in Canada and worldwide. Whilst advances in anatomical imaging to detect and monitor malignant disease have continued over the last few decades, limitations remain. Functional imaging, such as positron emission tomography (PET), has improved the sensitivity and specificity in detecting malignant disease. In combination with computed tomography (CT), PET is now commonly used in the oncology setting and is an integral part of many cancer patients' pathways. Although initially the CT component of the study was purely for attenuation of the PET imaging and to provide anatomical coregistration, many centers now combine the PET study with a diagnostic quality contrast enhanced CT to provide one stop staging, thus refining the patient's pathway. The commonest tracer used in everyday practice is FDG (F18-fluorodeoxyglucose). There are many more tracers in routine clinical practice and those with emerging roles, such as 11C-choline, useful in the imaging of prostate cancer; 11C-methionine, useful in imaging brain tumours; C11-acetate, used in imaging hepatocellular carcinomas; 18F-FLT, which can be used as a marker of cellular proliferation in various malignancies; and F18-DOPA and various 68Ga-somatostatin analogues, used in patients with neuroendocrine tumours. In this article we concentrate on FDG PETCT as this is the most commonly available and widely utilised tracer now used to routinely stage a number of cancers. PETCT alters the stage in approximately one third of patients compared to anatomical imaging alone. Increasingly, PETCT is being used to assess early metabolic response to treatment. Metabolic response can be seen much earlier than a change in the size/volume of the disease which is measured by standard CT imaging. This can aid treatment decisions in both in terms of modifying therapy and in addition to providing important prognostic information. Furthermore, it is helpful in patients with distorted anatomy from surgery or radiotherapy when there is suspicion of recurrent or residual disease. FDG PETCT is not specific for malignancy and can also be used for diagnosing and monitoring a number of inflammatory and infectious conditions that can be difficult to diagnose on anatomical imaging, some of which carry significant morbidity. FDG PETCT is increasingly used in patients with pyrexia of unknown origin and in patients with metastatic malignancies of unidentified primary on conventional imaging. This article reviews the uses of PETCT including an overview of the more common incidental lesions and conditions. It also provides guidance of how to approach a PETCT as a nonradionuclide radiologist and how to interpret a study in the multidisciplinary team setting. PMID- 26277235 TI - Finding the Truth in Medical Imaging: Painting the Picture of Appropriateness for Magnetic Resonance Imaging in Canada. AB - BACKGROUND: Questions about the appropriateness of medical imaging exams, particularly related to magnetic resonance exams, have arisen in recent years. However, the prevalence of inappropriate imaging in Canada is unclear as inappropriate exam proportion estimates are often based on studies from other countries. Hence, we sought to compare and summarize Canadian studies related to magnetic resonance imaging appropriateness. METHODS: We completed a systematic literature search identifying studies related to magnetic resonance appropriateness in Canada published between 2003 and 2013. Two researchers independently searched and evaluated the literature available. Articles that studied or discussed magnetic resonance appropriateness in Canada were selected based on titles, abstracts, and, where necessary, full article review. Articles relating solely to other modalities or countries were excluded, as were imaging appropriateness guidelines and reviews. RESULTS: Fourteen articles were included: 8 quantitative studies and 6 editorials/commentaries. The quantitative studies reported inappropriate proportions of magnetic resonance exams ranging from 2% 28.5%. Our review also revealed substantial variations among study methods and analyses. Common topics identified among editorials/commentaries included reasons for obtaining imaging in general and for selecting a specific modality, consequences of inappropriate imaging, factors contributing to demand, and suggested means of mitigating inappropriate medical imaging use. CONCLUSIONS: The available studies do not support the common claim that 30% of medical imaging exams in Canada are inappropriate. The actual proportion of inappropriate magnetic resonance exams has not yet been established conclusively in Canada. Further research, particularly on a widespread national scale, is needed to guide healthcare policies. PMID- 26277236 TI - Dual-Energy Multidetector Computed Tomography With Iodine Quantification in the Evaluation of Portal Vein Thrombosis: Is It Possible to Discard the Unenhanced Phase? PMID- 26277237 TI - Proteomics in cancer research: Are we ready for clinical practice? AB - Although genomics has delivered major advances in cancer prognostics, treatment and diagnostics, it still only provides a static image of the situation. To study more dynamic molecular entities, proteomics has been introduced into the cancer research field more than a decade ago. Currently, however, the impact of clinical proteomics on patient management and clinical decision-making is low and the implementations of scientific results in the clinic appear to be scarce. The search for cancer-related biomarkers with proteomics however, has major potential to improve risk assessment, early detection, diagnosis, prognosis, treatment selection and monitoring. In this review, we provide an overview of the transition of oncoproteomics towards translational oncology. We describe which lessons are learned from currently approved protein biomarkers and previous proteomic studies, what the pitfalls and challenges are in clinical proteomics applications, and how proteomic research can be successfully translated into medical practice. PMID- 26277238 TI - [Ultrahigh dose-rate, "flash" irradiation minimizes the side-effects of radiotherapy]. AB - PURPOSE: Pencil beam scanning and filter free techniques may involve dose-rates considerably higher than those used in conventional external-beam radiotherapy. Our purpose was to investigate normal tissue and tumour responses in vivo to short pulses of radiation. MATERIAL AND METHODS: C57BL/6J mice were exposed to bilateral thorax irradiation using pulsed (at least 40 Gy/s, flash) or conventional dose-rate irradiation (0.03 Gy/s or less) in single dose. Immunohistochemical and histological methods were used to compare early radio induced apoptosis and the development of lung fibrosis in the two situations. The response of two human (HBCx-12A, HEp-2) tumour xenografts in nude mice and one syngeneic, orthotopic lung carcinoma in C57BL/6J mice (TC-1 Luc+), was monitored in both radiation modes. RESULTS: A 17 Gy conventional irradiation induced pulmonary fibrosis and activation of the TGF-beta cascade in 100% of the animals 24-36 weeks post-treatment, as expected, whereas no animal developed complications below 23 Gy flash irradiation, and a 30 Gy flash irradiation was required to induce the same extent of fibrosis as 17 Gy conventional irradiation. Cutaneous lesions were also reduced in severity. Flash irradiation protected vascular and bronchial smooth muscle cells as well as epithelial cells of bronchi against acute apoptosis as shown by analysis of caspase-3 activation and TUNEL staining. In contrast, the antitumour effectiveness of flash irradiation was maintained and not different from that of conventional irradiation. CONCLUSION: Flash irradiation shifted by a large factor the threshold dose required to initiate lung fibrosis without loss of the antitumour efficiency, suggesting that the method might be used to advantage to minimize the complications of radiotherapy. PMID- 26277239 TI - [How to care for elderly patients with cognitive impairment?]. AB - Mild cognitive impairment occurs frequently with ageing, concerning memory complaint, attention and executive dysfunction without any consequence on the activities of daily living. They are strongly linked to the presence of vascular risk factors in adulthood. Nevertheless with the continuous progression of life expectancy, the incidence of dementia drastically increases after sixty-five years of age and the number of old people with dementia is expected to increase by 75% in 2030 in France. Caring for elderly patients with cancer needs to face the possibility of cognitive impairment and its consequences on a good comprehension of diagnosis and treatment and ability to properly take medication. Comprehensive geriatric assessment can help to diagnose cognitive impairment and evaluate the consequences on instrumental activities of daily living (IADL) and activities of daily living (ADL). Home care may be organised with the help of the family or social workers. Physiotherapy and speech rehabilitation are often useful. Assistance for housekeeping, shopping and cooking may be financed by social organisations such as APA in France. Complex cases must be referred to case managers in homes for patients suffering for Alzheimer's disease (MAIA) who liaise between doctors and home carers with good results. PMID- 26277240 TI - Total Bilateral Tarsal Coalition: A Case Report. AB - A 35-year-old male presented with pain and swelling of his right foot and ankle. His pain developed gradually and without overt pedal deformity. The radiologic examination revealed complete fusion of all tarsal bones of his right foot. Comparative radiographs of his left foot also showed complete tarsal coalition. Ankle osteoarthritis was diagnosed, and supportive treatment enabled the patient to return to an asymptomatic status and continue the duties of his employment. This case is presented to describe an adult patient with bilateral, massive tarsal coalition who was essentially asymptomatic until degenerative arthritic changes developed in one of his ankles. PMID- 26277241 TI - Screw Versus Plate Fixation for Chevron Osteotomy: A Retrospective Study. AB - The chevron osteotomy is a popular procedure used for the correction of moderate hallux abducto valgus deformity. Fixation is typically accomplished with Kirschner wires or bone screws; however, in cystic or osteoporotic bone, these could be inadequate, resulting in displacement of the capital fragment. We propose using a locking plate and interfragmental screw for fixation of the chevron osteotomy that could reduce the healing time and decrease the incidence of displacement. We performed a retrospective cohort study for chevron osteotomies on 75 feet (73 patients). The control groups underwent fixation with 1 screw in 30 feet (40%) and 2 screws in 30 feet (40%). A total of 15 feet (20%) were included in the locking plate and interfragmental screw group. The patients were followed up until bone healing was achieved at a median of 7 (range 6 to 14) weeks. Our hypothesis was that those treated with the locking plate and interfragmental screw would have a faster healing time and fewer incidents of capital fragment displacement compared with the 1- or 2-screw groups. The corresponding mean intervals to healing for the 1-screw group was 7.71 +/- 1.28 (range 6 to 10) weeks, for the 2-screw group was 7.27 +/- 1.57 (range 6 to 14) weeks, and for the locking plate and interfragmental screw group was 7.01 +/- 1.00 (range 6 to 9) weeks. One case of capital fragment displacement occurred in the single screw group and one in the 2-screw group. No displacement occurred in the locking plate and interfragmental screw group. Neither finding was statistically significant. However, we believe the locking plate and interfragmental screw could be a viable option in patients with osteoporotic and cystic bone changes for correction of hallux abducto valgus. PMID- 26277242 TI - Empty Toe Phenomenon: A Rare Presentation of Closed Degloving Injury of the Foot. AB - Traumatic degloving injuries of the lower extremity are commonly diagnosed by soft tissue deficits and separation of soft tissue planes. The management of open degloving injuries is well documented with established treatment protocols. Because closed degloving injuries of the lower extremity are so rare, the protocol management is not well established. Unlike open degloving injuries, evidence of soft tissue injury and detachment of the tissue planes can be subtle. Owing to the rarity of these injuries, little has been described regarding the long-term outcomes. In the present report, 2 closed degloving cases are presented. The first case presented is of a 27-year-old railroad worker who sustained a severe closed degloving injury of his foot with digital soft tissue envelope transposition. The second case involved a 60-year-old automobile manufacturer, whose foot was crushed by a hydraulic fork lift, creating a degloving injury of the third, fourth, and fifth toes. The follow-up duration from the date of injury for patient 1 was 26 months and for patients 2 was 16 months. The purpose of presenting these cases is to report these rare injuries with the treatment, complications, and outcomes. PMID- 26277243 TI - Operative Treatment for Osteoarthritis of the First Metatarsophalangeal Joint: Arthrodesis Versus Hemiarthroplasty. AB - Controversy remains whether hemiarthroplasty or arthrodesis results in better postoperative outcomes for patients who request surgery for advanced osteoarthritis of the first metatarsophalangeal joint. Therefore, we tested the primary null hypothesis that the 2 treatment groups would not differ in the postoperative American Orthopaedic Foot and Ankle Society hallux metatarsophalangeal interphalangeal scale scores after a follow-up period of >=1 year. Secondary analyses addressed the satisfaction rates, percentage of patients who would recommend the procedure, and unplanned repeat operation rates. A total of 58 primary arthrodeses and 36 hemiarthroplasties performed from January 2005 to December 2010 were evaluated at >=1 year postoperatively. At a mean average of 4 (range 1 to 7) years after surgery, the mean American Orthopaedic Foot and Ankle Society hallux metatarsophalangeal interphalangeal scale score was 77.5 +/- 18.5 in the arthrodesis group and 77.8 +/- 12.0 in the arthroplasty group (p = .93). The number of repeat operations did not differ between these 2 groups, and patients treated with hemiarthroplasty reported greater mean satisfaction (p = .04). These results showed that the symptom intensity and magnitude of disability were similar at >=1 year after arthrodesis or hemiarthroplasty for osteoarthritis of the first metatarsophalangeal joint, although the patients were subjectively more pleased with the results after hemiarthroplasty. PMID- 26277244 TI - Prosteatotic genes are associated with unsaturated fat suppression of saturated fat-induced hepatic steatosis in C57BL/6 mice. AB - Both high sugar and fat diets can induce prosteatotic genes, leading to obesity and obesity-associated diseases, including hepatic steatosis. Unsaturated fat/fatty acid (USFA) reduces high sugar-induced hepatic steatosis by inhibiting the induced prosteatotic genes. In contrast, it is still unclear how USFA ameliorates saturated fat/fatty acid (SFA)-induced hepatic steatosis. As sugar and fat have different transport and metabolic pathways, we hypothesized that USFA suppressed SFA-induced hepatic steatosis via a different set of prosteatotic genes. To test this, we implemented high SFA vs USFA diets and a control diet in C57BL/6 mice for 16 weeks. Severe hepatic steatosis was induced in mice fed the SFA diet. Among a nearly complete set of prosteatotic genes, only the stearoyl coenzyme a desaturase 1 (Scd1), cluster of differentiation 36 (Cd36), and peroxisome proliferator-activated receptor gamma (Ppargamma) genes that were differentially expressed in the liver could contribute to SFA-induced steatosis or the alleviative effect of USFA. That is, the SFA diet induced the expression of Cd36 and Ppargamma but not Scd1, and the USFA diet suppressed Scd1 expression and the induction of Cd36 and Ppargamma. These findings were mainly recapitulated in cultured hepatocytes. The essential roles of SCD1 and CD36 were confirmed by the observation that the suppression of SCD1 and CD36 with small interfering RNA or drug treatment ameliorated SFA-induced lipid accumulation in hepatocytes. We thus concluded that SCD1, CD36, and PPARgamma were essential to the suppression of SFA-induced hepatic steatosis by main dietary USFA, which may provide different therapeutic targets for reducing high-fat vs sugar-induced hepatic steatosis. PMID- 26277245 TI - Music in hospital. PMID- 26277246 TI - Music as an aid for postoperative recovery in adults: a systematic review and meta-analysis. AB - BACKGROUND: Music is a non-invasive, safe, and inexpensive intervention that can be delivered easily and successfully. We did a systematic review and meta analysis to assess whether music improves recovery after surgical procedures. METHODS: We included randomised controlled trials (RCTs) of adult patients undergoing surgical procedures, excluding those involving the central nervous system or head and neck, published in any language. We included RCTs in which any form of music initiated before, during, or after surgery was compared with standard care or other non-drug interventions. We searched MEDLINE, Embase, CINAHL, and Cochrane Central. We did meta-analysis with RevMan (version 5.2), with standardised mean differences (SMD) and random-effects models, and used Stata (version 12) for meta-regression. This study is registered with PROSPERO, number CRD42013005220. FINDINGS: We identified 4261 titles and abstracts, and included 73 RCTs in the systematic review, with size varying between 20 and 458 participants. Choice of music, timing, and duration varied. Comparators included routine care, headphones with no music, white noise, and undisturbed bed rest. Music reduced postoperative pain (SMD -0.77 [95% CI -0.99 to -0.56]), anxiety ( 0.68 [-0.95 to -0.41]), and analgesia use (-0.37 [-0.54 to -0.20]), and increased patient satisfaction (1.09 [0.51 to 1.68]), but length of stay did not differ (SMD -0.11 [-0.35 to 0.12]). Subgroup analyses showed that choice of music and timing of delivery made little difference to outcomes. Meta-regression identified no causes of heterogeneity in eight variables assessed. Music was effective even when patients were under general anaesthetic. INTERPRETATION: Music could be offered as a way to help patients reduce pain and anxiety during the postoperative period. Timing and delivery can be adapted to individual clinical settings and medical teams. FUNDING: None. PMID- 26277247 TI - Community-acquired pneumonia. AB - Community-acquired pneumonia causes great mortality and morbidity and high costs worldwide. Empirical selection of antibiotic treatment is the cornerstone of management of patients with pneumonia. To reduce the misuse of antibiotics, antibiotic resistance, and side-effects, an empirical, effective, and individualised antibiotic treatment is needed. Follow-up after the start of antibiotic treatment is also important, and management should include early shifts to oral antibiotics, stewardship according to the microbiological results, and short-duration antibiotic treatment that accounts for the clinical stability criteria. New approaches for fast clinical (lung ultrasound) and microbiological (molecular biology) diagnoses are promising. Community-acquired pneumonia is associated with early and late mortality and increased rates of cardiovascular events. Studies are needed that focus on the long-term management of pneumonia. PMID- 26277248 TI - Analysis of differentially expressed genes under UV-B radiation in the desert plant Reaumuria soongorica. AB - Reaumuria soongorica is one of the typical desert plants that present excellent tolerance to adverse environments. However, its molecular response to UV-B radiation remains poorly understood. To test the response and tolerance mechanisms of R. soongorica to the increasing UV-B radiation, the differentially expressed genes (DEGs) were investigated between the control and UV-B radiation groups. A total of 2150 DEGs were detected between the two groups, of which 561 were up-regulated and 1589 were down-regulated. For functional analysis, DEGs were divided into three groups: (i) Chloroplast-localized proteins, including photosynthesis-associated proteins, ribulose-phosphate-3-epimerase, and ATP dependent Clp protease. Their transcripts were inhibited, implying that the normal function of chloroplast was affected by UV-B radiation. (ii) Proteins involved in signaling transduction, such as phototropins and GTP-binding proteins. The transcriptional alternation of phototropins may reduce the penetration of UV-B radiation by regulating phototropism, stomatal opening, and chloroplast relocation. The down regulation of GTP-binding proteins may inhibit replication of potentially damaged DNA through preventing cell division; and (iii) proteins for lipid transfer and flavonoids biosynthesis. The up-regulation of these genes suggested that lipid transfer and flavonoids may have a protective function in response to UV-B radiation. Thus, UV-B radiation may lead to the disruption of chloroplasts function. The induction of genes for signal transduction and protective proteins may be a strategy for responding to UV-B radiation in R. soongorica. PMID- 26277249 TI - Genome-wide selection of superior reference genes for expression studies in Ganoderma lucidum. AB - Quantitative real-time polymerase chain reaction (qRT-PCR) is widely used for the accurate analysis of gene expression. However, high homology among gene families might result in unsuitability of reference genes, which leads to the inaccuracy of qRT-PCR analysis. The release of the Ganoderma lucidum genome has triggered numerous studies to be done on the homology among gene families with the purpose of selecting reliable reference genes. Based on the G. lucdum genome and transcriptome database, 38 candidate reference genes including 28 novel genes were systematically selected and evaluated for qRT-PCR normalization. The result indicated that commonly used polyubiquitin (PUB), beta-actin (BAT), and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) were unsuitable reference genes because of the high sequence similarity and low primer specificity. According to the evaluation of RefFinder, cyclophilin 5 (CYP5) was ranked as the most stable reference gene for 27 tested samples under all experimental conditions and eighteen mycelial samples. Based on sequence analysis and expression analysis, our study suggested that gene characteristic, primer specificity of high homologous genes, allele-specificity expression of candidate genes and under evaluation of reference genes influenced the accuracy and sensitivity of qRT-PCR analysis. This investigation not only revealed potential factors influencing the unsuitability of reference genes but also selected the superior reference genes from more candidate genes and testing samples than those used in the previous study. Furthermore, our study established a model for reference gene analysis by using the genomic sequence. PMID- 26277250 TI - Dipeptidyl peptidase-4 inhibitor, linagliptin, ameliorates endothelial dysfunction and atherogenesis in normoglycemic apolipoprotein-E deficient mice. AB - BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors have vasoprotective effects. This study investigated whether a recently approved DPP-4 inhibitor, linagliptin (Lina), suppresses atherogenesis in non-diabetic apolipoprotein-E deficient (ApoE(-/-)) mice, and examined its effects on endothelial function. METHODS AND RESULTS: Lina (10mg/kg/day) was administered orally to ApoE(-/-) mice for 20 weeks. Lina reduced atherogenesis without alteration of metabolic parameters including blood glucose level compared with control (P<0.05). Results of immunohistochemical analyses and quantitative RT-PCR demonstrated that Lina significantly decreased inflammatory molecule expression and macrophage infiltration in the atherosclerotic aorta. Lina administration to ApoE(-/-) mice for 9 weeks ameliorated endothelium-dependent vasodilation compared with that in untreated mice. Plasma active glucagon-like peptide-1 (GLP-1) level was significantly higher in the treated group (P<0.05). Exendin-4 (Ex-4), a GLP-1 analog, ameliorated endothelium-dependent vasodilation impaired by palmitic acid (PA) in wild-type mouse aortic segments. Ex-4 promoted phosphorylation of eNOS(Ser1177) and Akt, both of which were abrogated by PA, in human umbilical vein endothelial cells. In addition, Lina administration to ApoE(-/-) mice decreased oxidative stress, as determined by urinary 8-OHdG secretion and NADPH oxidase subunit expression in the abdominal aorta. CONCLUSION: Lina inhibited atherogenesis in non-diabetic ApoE(-/-) mice. Amelioration of endothelial dysfunction associated with a reduction of oxidative stress by GLP-1 contributes to the atheroprotective effects of Lina. PMID- 26277251 TI - Recent mechanistic and structural insights on class III viral fusion glycoproteins. AB - Enveloped viruses enter the cell by fusing their envelope with a cellular membrane. Fusion is catalyzed by conformational changes of viral glycoproteins from pre-fusion to post-fusion states. Structural studies have defined three classes of viral fusion glycoproteins. Class III comprises the fusion glycoproteins from rhabdoviruses (G), herpesviruses (gB), and baculoviruses (GP64). Although sharing the same fold, those glycoproteins exhibit striking differences in their modes of activation and interaction with the target membrane. Furthermore, for gB and GP64, only the post-fusion structure is known and the extent of their conformational change is still an unresolved issue. Further structural studies are therefore required to get a detailed insight in the working of those fusion machines. PMID- 26277252 TI - General practitioners adherence to recommendations from geriatric assessments made during teleconsultations for the elderly living in nursing homes. AB - OBJECTIVES: To determine the factors associated with general practitioners adherence to recommendations from geriatric assessments made during teleconsultations for the elderly living in nursing homes. STUDY DESIGN: Prospective cohort study in three nursing homes in Vendee, France, with access to teleconsultations from Challans Hospital. Teleconsultations with geriatric assessment for which recommendations were made by a geriatrician (n=69). MAIN OUTCOME MEASUREMENTS: Participants were separated into two groups based on the evidence of general practitioners adherence to recommendations 30 days after teleconsultation. Their adherence has been defined by the application by themselves supporting the elderly of prescription or organization of all recommendations made by the geriatrician during the teleconsultation. The type of recommendations was pharmacological and non-pharmacological treatments, and expert medical advice. The recorded data included the main reason of teleconsultation's request, age, sex, dementia diagnosis, multimorbidities scale, body mass index, Activities of Daily Living Scale, 4-items Geriatric Depression Scale, existence of a fall, and the Neuropsychiatric Inventory. Logistic regressions were performed to examine the factors associated with general practitioners adherence to recommendations from the geriatric assessment. RESULTS: General practitioners adherence to recommendations was made for 58 teleconsultations (86.3%). A fully adjusted logistic regression showed that general practitioners adherence to recommendations was associated with risk of depressive syndrome (OR=8.00, P=0.040) and expert medical advice's recommendations (OR=17.97, P=0.040). CONCLUSIONS: General practitioners adherence to recommendations from the geriatric assessment made during teleconsultations for elderly living in nursing homes is associated with the risk of depressive syndrome's existence and the expert medical advice recommendations. PMID- 26277253 TI - Cognitive frailty, a new target for healthy ageing. PMID- 26277254 TI - Effects of a six-week Pilates intervention on balance and fear of falling in women aged over 65 with chronic low-back pain: A randomized controlled trial. AB - OBJECTIVE: The purpose of our study was to evaluate the effects of six weeks of Pilates regarding functional balance, fear of falling and pain in community living women older than 65 years old with chronic low-back pain. STUDY DESIGN: A single blind controlled randomized trial of six weeks of Pilates in addition to physiotherapy treatment (n=50) vs. physiotherapy treatment alone (n=47) was conducted on 97 community living women (71.14 +/- 3.30 years) with chronic low back pain (CLBP). MAIN OUTCOME MEASURES: Main outcome measures were fear of falling (FoF), assessed by the Falls Efficacy Scale-international; functional mobility and balance, measured with the Timed up and Go Test; and pain, evaluated using the numeric rating scale. RESULTS: Only the Pilates group showed improvement in FoF (ES; d=.68) and functional mobility and balance (ES; d=1.12) after treatment, and also had better results in pain (ES; d=1.46) than the physiotherapy-only group. CONCLUSIONS: Six weeks of Pilates exercises may be effective in fall prevention through the improvement of FoF, functional balance, and pain in Spanish women over 65 years old with CLBP. PMID- 26277255 TI - Exploring the critical quality attributes and models of smart homes. AB - Research on smart homes has significantly increased in recent years owing to their considerably improved affordability and simplicity. However, the challenge is that people have different needs (or attitudes toward smart homes), and provision should be tailored to individuals. A few studies have classified the functions of smart homes. Therefore, the Kano model is first adopted as a theoretical base to explore whether the functional classifications of smart homes are attractive or necessary, or both. Second, three models and test user attitudes toward three function types of smart homes are proposed. Based on the Kano model, the principal results, namely, two "Attractive Quality" and nine "Indifferent Quality" items, are found. Verification of the hypotheses also indicates that the entertainment, security, and automation functions are significantly correlated with the variables "perceive useful" and "attitude." Cost consideration is negatively correlated with attitudes toward entertainment and automation. Results suggest that smart home providers should survey user needs for their product instead of merely producing smart homes based on the design of the builder or engineer. PMID- 26277256 TI - Hypovitaminosis D and frailty: Epiphenomenon or causal? AB - Vitamin D is not only a key component in the maintenance of calcium homeostasis and bone health, but has also been implicated in a myriad of other non-skeletal biologic systems. The frailty syndrome is an emerging and increasingly important concept in the field of aging, with the "physical" clinical phenotype being initially presented as the operational definition. The relationship between vitamin D and frailty is postulated to be largely mediated via the development of sarcopenia, a condition characterised by a combination of the reduction of muscle mass, plus either muscle strength or performance. Several molecular pathways may account for the development of muscle wasting in sarcopenia, and there is mounting epidemiological and laboratory evidence that supports a role of vitamin D on muscle cell proliferation and function. Although observational studies on vitamin D and frailty have not definitively established an independent relationship, interventional studies of the effect of supplemental vitamin D have yielded a positive influence on the frailty status, mainly via improvements in the physical performance. Further studies that are adequately powered and well designed are warranted in an attempt to establish a causal relationship between vitamin D and frailty. In the absence of a consensus on the definition of the frailty syndrome, an appropriate and well-validated measure instrument for this health outcome would be recommended in the realm of frailty research. PMID- 26277257 TI - FRAX--Where are we now? AB - Bone mineral density (BMD) measurements have been widely used in clinical practice for the diagnosis of osteoporosis, monitoring of treatment, and prediction of fracture risk. However, although BMD values show high specificity for prediction of fractures, their sensitivity is quite low. Fracture risk algorithms such as FRAX improve prediction by including clinical risk factors that act independently of BMD. This mini-review discusses the strengths and limitations of FRAX relevant to its use in clinical practice. PMID- 26277258 TI - Distorted estimates of implicit and explicit learning in applications of the process-dissociation procedure to the SRT task. AB - We investigated potential biases affecting the validity of the process dissociation (PD) procedure when applied to sequence learning. Participants were or were not exposed to a serial reaction time task (SRTT) with two types of pseudo-random materials. Afterwards, participants worked on a free or cued generation task under inclusion and exclusion instructions. Results showed that pre-experimental response tendencies, non-associative learning of location frequencies, and the usage of cue locations introduced bias to PD estimates. These biases may lead to erroneous conclusions regarding the presence of implicit and explicit knowledge. Potential remedies for these problems are discussed. PMID- 26277259 TI - Obstructive Gastric Pseudotumor Caused by Cytomegalovirus in an AIDS Patient: A Case Report and Review of Surgical Treatment. AB - BACKGROUND: Cytomegalovirus (CMV) is a common opportunistic pathogen in patients with HIV. It is also a major cause of gastrointestinal ulcers in patients with acquired immunodeficiency syndrome (AIDS). CMV pseudotumor in the stomach is a rare cause of digestive tract obstruction. CASE REPORT: In this study we report a male patient infected with HIV in 2002. In 2014 he evolved C3 stage AIDS with pre pyloric gastric ulcer which provoked deformity and pseudotumoral aspect of the gastric outlet. Endoscopic biopsy confirmed CMV infection. He underwent Roux-en-Y gastroenteroanastomosis with good recovery. CONCLUSIONS: CMV infection should be considered as an agent in gastric lesions in HIV-infected patients. Roux-en-Y gastroenteroanastomosis is a surgical option for this group of patients, allowing improvements in quality of life and decreasing risks of perioperative complications. PMID- 26277260 TI - The COP9 SIGNALOSOME Is Required for Postembryonic Meristem Maintenance in Arabidopsis thaliana. AB - Cullin-RING E3 ligases (CRLs) regulate different aspects of plant development and are activated by modification of their cullin subunit with the ubiquitin-like protein NEDD8 (NEural precursor cell expressed Developmentally Down-regulated 8) (neddylation) and deactivated by NEDD8 removal (deneddylation). The constitutively photomorphogenic9 (COP9) signalosome (CSN) acts as a molecular switch of CRLs activity by reverting their neddylation status, but its contribution to embryonic and early seedling development remains poorly characterized. Here, we analyzed the phenotypic defects of csn mutants and monitored the cullin deneddylation/neddylation ratio during embryonic and early seedling development. We show that while csn mutants can complete embryogenesis (albeit at a slower pace than wild-type) and are able to germinate (albeit at a reduced rate), they progressively lose meristem activity upon germination until they become unable to sustain growth. We also show that the majority of cullin proteins are progressively neddylated during the late stages of seed maturation and become deneddylated upon seed germination. This developmentally regulated shift in the cullin neddylation status is absent in csn mutants. We conclude that the CSN and its cullin deneddylation activity are required to sustain postembryonic meristem function in Arabidopsis. PMID- 26277261 TI - Gene Body CG and CHG Methylation and Suppression of Centromeric CHH Methylation are Mediated by DECREASE IN DNA METHYLATION1 in Rice. PMID- 26277262 TI - Proton Pump Inhibitors and Myocardial Infarction. PMID- 26277263 TI - Stabilization challenges and formulation strategies associated with oral biologic drug delivery systems. AB - Delivery of proteins to mucosal tissues of GI tract typically utilize formulations which protect against proteolysis and target the mucosal tissues. Using case studies from literature and the authors' own work, the in-process stability and solid state storage stability of biopharmaceuticals formulated in delivery systems designed for oral delivery to the GI tract will be reviewed. Among the range of delivery systems, biodegradable polymer systems for protection and controlled release of proteins have been the most studied; hence these systems will be covered in greater depth. These delivery systems include polymeric biodegradable microspheres or nanospheres that contain proteins or vaccines, which are designed to reduce the number of administrations/inoculations and the total protein dose required to achieve the desired biological effect. Specifically, this review will include a landscape survey of the systems that have been studied, the manufacturing processes involved, stability through the manufacturing process, key pharmaceutical formulation parameters that impact stability of the encased proteins, and storage stability of the encapsulated proteins in these delivery systems. PMID- 26277264 TI - "Compliance and patching and atropine amblyopia treatments"--Reply to Letter to the Editor. PMID- 26277266 TI - Expert-novice differences in SMR activity during dart throwing. AB - Previous evidence suggests that augmented sensorimotor rhythm (SMR) activity is related to the superior regulation of processing cognitive-motor information in motor performance. However, no published studies have examined the relationship between SMR and performance in precision sports; thus, this study examined the relationship between SMR activity and the level of skilled performance in tasks requiring high levels of attention (e.g., dart throwing). We hypothesized that skilled performance would be associated with higher SMR activity. Fourteen dart throwing experts and eleven novices were recruited. Participants were requested to perform 60 dart throws while EEG was recorded. The 2(Group: Expert, Novice)*2(Time window: -2000 ms to -1000 ms, -1000 ms to 0 ms) ANOVA showed that the dart-throwing experts maintained a relatively higher SMR power than the novices before dart release. These results suggest that SMR might reflect the adaptive regulation of cognitive-motor processing during the preparatory period. PMID- 26277265 TI - Unoprostone activation of BK (KCa1.1) channel splice variants. AB - This investigation was conducted to study the relationship between intracellular Ca(2+) and activation of large conductance Ca(2+)-activated K(+) (BK) currents by unoprostone, the first synthetic docosanoid. We used HEK293 cells stably transfected with two BK channel splice variants, one sensitive to unoprostone and the other insensitive. We examined the effects of unoprostone on channel activity in excised inside-out patches and cell-attached patches. The half-maximal stimulation of the sensitive BK channels by Ca(2+) was shifted from 3.4+/-0.017 nM to 0.81+/-.0058 nM in the presence of 10 nM unoprostone. There was no effect on insensitive channels even at unoprostone concentrations as high as 1000 nM. There was no effect of unoprostone on the voltage dependence of the BK channels. Changes in open probability and effects of Ca(2+) and unoprostone were best described by a synergistic binding model. These data would suggest that Ca(2+) and unoprostone were binding to sites close to one another on the channel protein and that unoprostone binding causes the affinity of the calcium binding site to increase. This idea is consistent with three dimensional models of the Ca(2+) binding site and a putative unoprostone binding domain. Our results have important implications for the clinical use of unoprostone to activate BK channels. Channel activation will be limited if intracellular Ca(2+) is not elevated. PMID- 26277267 TI - Echocardiography in Acute Heart Failure: Current Perspectives. AB - In contrast to chronic heart failure (HF), the use of echocardiography in acute HF (AHF) is less well defined, both in clinical practice and in clinical trials. Current guidelines recommend the utility of echocardiography as an adjunct diagnostic tool in the clinical setting of new-onset or decompensated HF. However, despite its unique advantages as the only practical imaging modality in AHF, echocardiography poses unique challenges in this setting. Data from early phase clinical studies and trials provide evidence that echocardiographic end points can be clinically meaningful surrogate end points as a means to track response to treatment in AHF; however, the optimal timing and selection of echocardiographic measures is under active investigation. In addition, despite a number of studies indicating that certain echocardiographic measures of cardiac function are predictive of post-discharge prognosis, the role of echocardiography as a tool for patient classification and risk determination in AHF is less well defined. Importantly, it is unclear whether echocardiography can be used to phenotype and select AHF patients for interventions. In this article, we (1) appraise the current evidence for use of echocardiographic measures in AHF, (2) identify knowledge gaps regarding optimal use of echocardiography in AHF, and (3) assess the evidence for echocardiography as a prognosis determination and risk stratification tool in AHF. PMID- 26277268 TI - A comprehensive review on pre-treatment strategy for lignocellulosic food industry waste: Challenges and opportunities. AB - Lignocellulose is a generic term used to describe plant biomass. It is the most abundant renewable carbon resource in the world and is mainly composed of lignin, cellulose and hemicelluloses. Most of the food and food processing industry waste are lignocellulosic in nature with a global estimate of up to 1.3 billion tons/year. Lignocellulose, on hydrolysis, releases reducing sugars which is used for the production of bioethanol, biogas, organic acids, enzymes and biosorbents. However, structural conformation, high lignin content and crystalline cellulose hinder its use for value addition. Pre-treatment strategies facilitate the exposure of more cellulose and hemicelluloses for enzymatic hydrolysis. The present article confers about the structure of lignocellulose and how it influences enzymatic degradation emphasising the need for pre-treatments along with a comprehensive analysis and categorisation of the same. Finally, this article concludes with a detailed discussion on microbial/enzymatic inhibitors that arise post pre-treatment and strategies to eliminate them. PMID- 26277269 TI - Explicit verbal memory impairments associated with brain functional deficits and morphological alterations in patients with generalized anxiety disorder. AB - BACKGROUND: Generalized anxiety disorder (GAD) is associated with brain function and morphological alterations. This study investigated explicit verbal memory impairment in patients with GAD in terms of brain functional deficits in combination with morphologic changes. METHODS: Seventeen patients with GAD and 17 healthy controls matched for age, sex, and education level underwent high resolution T1-weighted MRI and fMR imaging at 3 T during explicit verbal memory tasks with emotionally neutral and anxiety-inducing words. RESULTS: In response to the neutral words, the patients showed significantly lower activities in the regions of the hippocampus (Hip), middle cingulate gyrus (MCG), putamen (Pu) and head of the caudate nucleus (HCd) compared with healthy controls. In response to the anxiety-inducing words, the patients showed significantly higher activities in the ventrolateral prefrontal cortex and precentral gyrus. However, they showed lower activities in the Hip, MCG, Pu and HCd. In addition, patients with GAD showed a significant reduction in gray matter volumes, especially in the regions of the Hip, midbrain, thalamus, insula and superior temporal gyrus, compared with healthy controls. LIMITATIONS: This study examined a small sample sizes in each of the groups, and there was no consideration of a medication effect on brain activity and volume changes. CONCLUSIONS: This study provides evidence for the association between brain functional deficits and morphometric alterations in an explicit verbal memory task for patients with GAD. This finding is helpful for understanding explicit verbal memory impairment in connection with GAD symptoms. PMID- 26277270 TI - Mood instability in bipolar disorder type I versus type II-continuous daily electronic self-monitoring of illness activity using smartphones. AB - BACKGROUND: A substantial proportion of patients with bipolar disorder remain symptomatic during inter-episode periods, and mood instability is associated with high risk of relapse and hospitalization. Few studies have investigated long-term daily illness activity and none has compared bipolar type I and II using daily data. The objectives were to investigate differences in daily illness activity between bipolar disorder type I and II. METHODS: A smartphone-based system for self-monitoring was developed. A total of 33 patients treated in a mood clinic used the system for daily self-monitoring during a median period of 310 days [IQR 189; 437]. Data presented summarize over 8500 observations. RESULTS: Patients with bipolar disorder type II (n=20), compared to patients with bipolar disorder type I (n=13), experienced a significant lower mean level of mood on a scale from -3; +3 (-0.54 (95% CI: -0.74; -0.35) versus -0.19 (95% CI: -0.35; -0.02), p=0.02), less time euthymic (51.0% (95% CI: 36.4; 65.7) versus 74.5% (95% CI: 62.4; 86.7), p=0.03) and a higher proportion of time with depressive symptoms (45.1% (95% CI: 30.6; 59.5) versus 18.8% (95% CI: 6.9; 30.7), p=0.01). The proportion of time spent with (hypo)manic symptoms did not differ (2.7% (95% CI: 0.1; 5.5) versus 5.5% (95% CI: 3.1; 7.8), p=0.17). LIMITATIONS: Patients received different types, doses and combinations of psychopharmacological treatment. CONCLUSION: Euthymia was obtained for a substantial proportion of time in patients with bipolar disorder type I, but despite on-going treatment only for half of the time for patients with bipolar disorder type II. This emphasizes the need for improving treatment strategies for bipolar disorder type II. PMID- 26277272 TI - Skin lesions on yellowfin tuna Thunnus albacares from Gulf of Mexico outer continental shelf: Morphological, molecular, and histological diagnosis of infection by a capsalid monogenoid. AB - We characterize lesion-associated capsaline infections on yellowfin tuna, Thunnus albacares, in the Gulf of Mexico by comparing our specimens with published descriptions and museum specimens ascribed to Capsala biparasiticum and its synonyms: vouchers of C. biparasiticum from parasitic copepods; the holotype of Capsala neothunni; and vouchers of Capsala abidjani. Those from parasitic copepods differed by having a small, rounded body, large anterior attachment organs, closely spaced dorsomarginal body sclerites, small testes, and a short and wide testicular field. No morphometric feature in the holotype of C. neothunni ranged outside of that reported for the newly-collected specimens, indicating conspecificity of our specimens. The specimens of C. abidjani differed by having a large anterior attachment organ, few and dendritic testes, and a short, wide testicular field. Large subunit ribosomal DNA (28S) sequences grouped our specimens and Capsala sp. as sister taxa and indicated a phylogenetic affinity of Nasicola klawei. The haptoral attachment site comprised a crater-like depression surrounded by a blackish-colored halo of extensively rugose skin, with abundant pockmarked-like, irregularly-shaped oblong or semi-circular epidermal pits surrounding these attachment sites. Histology confirmed extensive folding of epidermis and underlying stratum laxum, likely epidermal hyperplasia, foci of weak cell-to-cell adhesions among apical malpighian cells as well as that between stratum germinativum and stratum laxum, myriad goblet cells in epidermis, rodlet cells in apical layer of epidermis, and lymphocytic infiltrates and melanin in dermis. The present study comprises (i) the first published report of this parasite from yellowfin tuna captured in the Gulf of Mexico-NW Atlantic Ocean Basin, (ii) confirmation of its infection on the skin (rather than on a parasitic copepod), (iii) the first molecular data for this capsaline, and (iv) the first observations of histopathological changes associated with a capsalid infection on a wild-caught epipelagic fish. PMID- 26277271 TI - The role of self-blame and worthlessness in the psychopathology of major depressive disorder. AB - BACKGROUND: Cognitive models predict that vulnerability to major depressive disorder (MDD) is due to a bias to blame oneself for failure in a global way resulting in excessive self-blaming emotions, decreased self-worth, hopelessness and depressed mood. Clinical studies comparing the consistency and coherence of these symptoms in order to probe the predictions of the model are lacking. METHODS: 132 patients with remitted MDD and no relevant lifetime co-morbid axis-I disorders were assessed using a phenomenological psychopathology-based interview (AMDP) including novel items to assess moral emotions (n=94 patients) and the structured clinical interview-I for DSM-IV-TR. Cluster analysis was employed to identify symptom coherence for the most severe episode. RESULTS: Feelings of inadequacy, depressed mood, and hopelessness emerged as the most closely co occurring and consistent symptoms (>=90% of patients). Self-blaming emotions occurred in most patients (>80%) with self-disgust/contempt being more frequent than guilt, followed by shame. Anger or disgust towards others was experienced by only 26% of patients. 85% of patients reported feelings of inadequacy and self blaming emotions as the most bothering symptoms compared with 10% being more distressed by negative emotions towards others. LIMITATIONS: Symptom assessment was retrospective, but this is unlikely to have biased patients towards particular emotions relative to others. CONCLUSIONS: As predicted, feelings of inadequacy and hopelessness were part of the core depressive syndrome, closely co occurring with depressed mood. Self-blaming emotions were highly frequent and bothering but not restricted to guilt. This calls for a refined assessment of self-blaming emotions to improve the diagnosis and stratification of MDD. PMID- 26277273 TI - Utility of hand-held devices in diagnosis and triage of cardiovascular emergencies. Observations during implementation of a PACS-based system in an acute aortic syndrome (AAS) network. AB - BACKGROUND: Prompt diagnosis and early referral to specialized centers is critical for patients presenting with cardiovascular emergencies, including acute aortic syndromes (AAS). Prior data has suggested that mobile access to imaging studies with hand-held devices can accelerate diagnosis and management. OBJECTIVE: We conducted a study to determine the diagnostic accuracy of a hand held device compared to conventional dedicated work-stations for diagnosing a spectrum of cardiovascular emergencies, predominantly acute aortic pathology. METHODS: This study included 104 cases who underwent computed tomography (CT) scan during "on-call'' hours between January, 2013 and August, 2014 for suspected AAS. Assessment was performed on a hand-held device independently by two readers using an iPhone5 connected via secure connection to web-based PACS servers. The subsequent interpretation from a dedicated workstation coupled with the diagnosis at the time of discharge was used as the reference standard for determining the presence or absence of an acute abnormality. Sensitivity and Specificity were calculated on a per patient basis. RESULTS: Readers' sensitivity and specificity using the hand-held device to diagnose acute chest pathology were calculated. Hand-held device evaluation was determined to have a sensitivity of 85.2% and a specificity of 98.6% by reader A and a sensitivity of 96.3% and specificity of 100% by reader B. Of 103 cases interpreted by both readers, the readers agreed about the diagnosis in 98 cases (95.1%). CONCLUSION: This study demonstrates that hand-held devices can be a potential useful tool to assist in diagnosis and triage of patients presenting with cardiovascular emergencies. Further studies are needed to assess the impact of screen size and resolution. PMID- 26277274 TI - T cell metabolic reprogramming and plasticity. AB - Upon antigen stimulation, small and quiescent naive T cells undergo an approximately 24h growth phase followed by rapid proliferation. Depending on the nature of the antigen and cytokine milieu, these proliferating T cells differentiate into distinctive functional subgroups that are essential for appropriate immune defense and regulation. T cells undergo a characteristic metabolic rewiring that fulfills the dramatically increased bioenergetic and biosynthetic demands during the transition between resting, activation and differentiation. Beyond this, T cells are distributed throughout the body and are able to function in a wide range of physio-pathological environments, including some with a dramatic metabolic derangement. As such, T cells must quickly respond to and adapt to fluctuations in environmental nutrient levels. We consider such responsiveness and adaptation in terms of metabolic plasticity, that is, an evolutionarilly selected process which allows T cells to illicit robust immune functions in response to either a continuous or disrupted nutrient supply. In this review, we illustrate the relevant metabolic pathways in T cells and discuss the ability of T cells to change their metabolic substrates in response to changes in the environment. PMID- 26277276 TI - Delineation of BmSXP antibody V-gene usage from a lymphatic filariasis based immune scFv antibody library. AB - Phage display technology is an important tool for antibody generation or selection. This study describes the development of a scFv library and the subsequent analysis of identified monoclonal antibodies against BmSXP, a recombinant antigen for lymphatic filariasis. The immune library was generated from blood of lymphatic filariasis infected individuals. A TA based intermediary cloning approach was used to increase cloning efficiency for the library construction process. A diverse immune scFv library of 10(8) was generated. Six unique monoclonal antibodies were identified from the 50 isolated clones against BmSXP. Analysis of the clones showed a bias for the IgHV3 and Vkappa1 (45.5%) and IgHV2 and Vkappa3 (27.3%) gene family. The most favored J segment for light chain is IgKJ1 (45.5%). The most favored D and J segment for heavy chain are IgHD6-13 (75%) and IgHJ3 (47.7%). The information may suggest a predisposition of certain V genes in antibody responses against lymphatic filariasis. PMID- 26277275 TI - Metabolic regulation of T cell differentiation and function. AB - Upon encountering pathogens, T cells mount immune responses by proliferating, increasing cellular mass and differentiating. These cellular changes impose significant energetic challenges on T cells. It was believed that TCR and cytokine-mediated signaling are dominant dictators of T cell-mediated immune responses. Recently, it was recognized that T cells utilize metabolic transporters and metabolic sensors that allow them to rapidly respond to nutrient limiting inflammatory environments. Metabolic sensors allow T cells to find a balance between energy consumption (anabolic metabolism) and production (catabolic metabolism) in order to mount effective immune responses. Also, metabolic regulators interact with cytokine-dependent transcriptional regulators, suggesting a more integrative and advanced model of T cell activation and differentiation. In this review, we will discuss recent discoveries regarding the roles of metabolic regulators in effector and memory T cell development and their interaction with canonical transcription factors. PMID- 26277277 TI - Immunological evaluation of OMV(PagL)+Bap(1-487aa) and AbOmpA(8-346aa)+Bap(1 487aa) as vaccine candidates against Acinetobacter baumannii sepsis infection. AB - Acinetobacter baumannii is an important nosocomial pathogen that causes a high morbidity and mortality rate in infected patients with sepsis form. The surface exposed virulence proteins and serum resistance factors helping to dissemination of this bacterium to bloodstream are the most promising vaccine candidates against this microorganism. In this project we immunologically evaluated OMV(PagL)+Bap(1-487aa) and AbOmpA (8-346aa)+Bap(1-487aa) as combination forms as well as Bap(1-487aa), AbOmpA(8-346aa) and OMV(PagL) singly, with addition of alum adjuvant as vaccine candidates. The titers of total IgG, IgG1 and IgG2c as well as concentration of IL-4 and IFN-gamma and survival rates were measured in a C57BL/6 murine model with disseminated sepsis. The ratio of IgG1/IgG2c and profile of IL-4/IFN-gamma in OMV (PagL)+Bap (1-487aa) formulation shows the humoral and cellular immune responses have been induced robustly and have created a full protection against A. baumannii ATCC 19606 and MDR AB-44 strains. We found that the two combination vaccine candidates were protective and induced both Th1 and Th2 responses. PMID- 26277279 TI - Metformin and cancer: Between the bioenergetic disturbances and the antifolate activity. AB - For decades, metformin has been the first-line drug for the treatment of type II diabetes mellitus, and it thus is the most widely prescribed antihyperglycemic drug. Retrospective studies associate the use of metformin with a reduction in cancer incidence and cancer-related death. However, despite extensive research about the molecular effects of metformin in cancer cells, its mode of action remains controversial. In this review, we summarize the current molecular evidence in an effort to elucidate metformin's mode of action against cancer cells. Some authors describe that metformin acts directly on mitochondria, inhibiting complex I and restricting the cell's ability to cope with energetic stress. Furthermore, as the drug interrupts the tricarboxylic acid cycle, metformin-induced alteration of mitochondrial function leads to a compensatory increase in lactate and glycolytic ATP. It has also been reported that cell cycle arrest, autophagy, apoptosis and cell death induction is mediated by the activation of AMPK and Redd1 proteins, thus inhibiting the mTOR pathway. Additionally, unbiased metabolomics studies have provided strong evidence to support that metformin alters the methionine and folate cycles, with a concomitant decrease in nucleotide synthesis. Indeed, purines such as thymidine or hypoxanthine restore the proliferation of tumor cells treated with metformin in vitro. Consequently, some authors prefer to refer to metformin as an "antimetabolite drug" rather than a "mitochondrial toxin". Finally, we also review the current controversy concerning the relationship between the experimental conditions of in vitro-reported effects and the plasma concentrations achieved by chronic treatment with metformin. PMID- 26277278 TI - The repetitive portion of the Xenopus IgH Mu switch region mediates orientation dependent class switch recombination. AB - Vertebrates developed immunoglobulin heavy chain (IgH) class switch recombination (CSR) to express different IgH constant regions. Most double-strand breaks for Ig CSR occur within the repetitive portion of the switch regions located upstream of each set of constant domain exons for the Iggamma, Igalpha or Igepsilon heavy chain. Unlike mammalian switch regions, Xenopus switch regions do not have a high G-density on the non-template DNA strand. In previous studies, when Xenopus SMU DNA was moved to the genome of mice, it is able to support substantial CSR when it is used to replace the murine Sgamma1 region. Here, we tested both the 2kb repetitive portion and the 4.6 kb full-length portions of the Xenopus SMU in both their natural (forward) orientation relative to the constant domain exons, as well as the opposite (reverse) orientation. Consistent with previous work, we find that the 4.6 kb full-length SMU mediates similar levels of CSR in both the forward and reverse orientations. Whereas, the forward orientation of the 2kb portion can restore the majority of the CSR level of the 4.6 kb full-length SMU, the reverse orientation poorly supports R-looping and no CSR. The forward orientation of the 2kb repetitive portion has more GG dinucleotides on the non template strand than the reverse orientation. The correlation of R-loop formation with CSR efficiency, as demonstrated in the 2kb repetitive fragment of the Xenopus switch region, confirms a role played by R-looping in CSR that appears to be conserved through evolution. PMID- 26277280 TI - Challenges and achievements in the therapeutic modulation of aquaporin functionality. AB - Aquaporin (AQP) water and solute channels have basic physiological functions throughout the human body. AQP-facilitated water permeability across cell membranes is required for rapid reabsorption of water from pre-urine in the kidneys and for sustained near isosmolar water fluxes e.g. in the brain, eyes, inner ear, and lungs. Cellular water permeability is further connected to cell motility. AQPs of the aquaglyceroporin subfamily are necessary for lipid degradation in adipocytes and glycerol uptake into the liver, as well as for skin moistening. Modulation of AQP function is desirable in several pathophysiological situations, such as nephrogenic diabetes insipidus, Sjogren's syndrome, Meniere's disease, heart failure, or tumors to name a few. Attempts to design or to find effective small molecule AQP inhibitors have yielded only a few hits. Challenges reside in the high copy number of AQP proteins in the cell membranes, and spatial restrictions in the protein structure. This review gives an overview on selected physiological and pathophysiological conditions in which modulation of AQP functions appears beneficial and discusses first achievements in the search of drug-like AQP inhibitors. PMID- 26277281 TI - Development and field testing of a consumer shared decision-making training program for adults with low literacy. AB - OBJECTIVE: Given the scarcity of shared decision-making (SDM) interventions for adults with low literacy, we created a SDM training program tailored to this population to be delivered in adult education settings. METHODS: Formative evaluation during program development included a review of the problem and previous efforts to address it, qualitative interviews with the target population, program planning and field testing. RESULTS: A comprehensive SDM training program was developed incorporating core SDM elements. The program aimed to improve students' understanding of SDM and to provide them with the necessary skills (understanding probabilistic risks and benefits, personal values and preferences) and self-efficacy to use an existing set of questions (the AskShareKnow questions) as a means to engage in SDM during healthcare interactions. CONCLUSIONS: There is an ethical imperative to develop SDM interventions for adults with lower literacy. Generic training programs delivered direct-to-consumers in adult education settings offer promise in a national and international environment where too few initiatives exist. PRACTICE IMPLICATIONS: Formative evaluation of the program offers practical insights into developing consumer-focused SDM training. The content of the program can be used as a guide for future efforts to engage consumers in SDM. PMID- 26277282 TI - Acceptability, feasibility and effectiveness of an eHealth behaviour intervention using self-regulation: 'MyPlan'. AB - OBJECTIVE: The study aims to evaluate the acceptability, feasibility and effectiveness of the eHealth intervention 'MyPlan', which targets health behaviour in adults. METHODS: Flemish adults were randomly allocated to a control (n=155), or one of the three intervention groups: a physical activity (PA) (n=158), a fruit intake (n=161) or a vegetable intake group (n=48). PA, fruit or vegetable intake were measured at the start and after one month. RESULTS: Adults with low education, and over 40 years evaluated the personal advice and action plans as more motivating, but also the personal advice as too long than adults with high education and younger adults. Overall, 48% completed the follow-up module after one week, and only 24% after one month. At one-month follow-up, the fruit intake intervention resulted in more fruit intake (F=9.5, p=0.003) and the PA intervention in a higher total physically activity level (F=5.6, p=0.020) than the control group. There was no effect for vegetable intake. CONCLUSION: 'MyPlan' was feasible and acceptable, and has the potential to increase PA levels, and fruit and vegetable intake. PRACTICE IMPLICATIONS: Adaptations to the content of the intervention are further needed, and more attention is needed to motivate participants to complete the different follow-up parts. PMID- 26277284 TI - Re-orientation of human resources for health: a great challenge for the Brazilian National Health System. AB - OBJECTIVES: To present the data available and discuss the progress, current advances and challenges of the initiatives, current policies and guidance implemented by the Health and Education Ministries in Brazil to target transformation of health teaching in order to improve the health care offered by the Brazilian National Health System. STUDY DESIGN: Literature review. METHODS: Documentary analysis and review of articles identified in a search of electronic databases, along with reports and documents acquired from the Health and Education Ministries between 1988 and 2013. RESULTS: This study identified some important initiatives, including the Programme for the Encouragement of Curricular Changes in Medical Courses (PROMED), implemented in 2002 for medical courses alone. Inspired by PROMED and covering a wider range of graduate courses, the National Programme for Re-orientation of Health Professionals was implemented in 2005. This initiative launched its third edition in 2012, covering 14 health professional areas. Another relevant innovation was the National Policy of Permanent Health Education, implemented in 2007, with the goal of transforming public health services into a locus of teaching-learning through working. The Unified Health System Open University was also implemented. CONCLUSIONS: There is general concern and ongoing actions involving different sectors in Brazil in an attempt to improve the health of the Brazilian population in the future. However, the changes pursued involve deep transformations and may take considerable time. PMID- 26277285 TI - Who's afraid of the nanny state? Introduction to a symposium. PMID- 26277283 TI - Clinicians' recognition and management of emotions during difficult healthcare conversations. AB - OBJECTIVE: To examine the most commonly reported emotions encountered among healthcare practitioners when holding difficult conversations, including frequency and impact on care delivery. METHODS: Interprofessional learners from a range of experience levels and specialties completed self-report questionnaires prior to simulation-based communication workshops. Clinicians were asked to describe up to three emotions they experienced when having difficult healthcare conversations; subsequent questions used Likert-scales to measure frequency of each emotion, and whether care was affected. RESULTS: 152 participants completed questionnaires, including physicians, nurses, and psychosocial professionals. Most commonly reported emotions were anxiety, sadness, empathy, frustration, and insecurity. There were significant differences in how clinicians perceived these different emotions affecting care. Empathy and anxiety were emotions perceived to influence care more than sadness, frustration, and insecurity. CONCLUSIONS: Most clinicians, regardless of clinical experience and discipline, find their emotional state influences the quality of their care delivery. Most clinicians rate themselves as somewhat to quite capable of recognizing and managing their emotions, acknowledging significant room to grow. PRACTICE IMPLICATIONS: Further education designed to increase clinicians' recognition of, reflection on, and management of emotion would likely prove helpful in improving their ability to navigate difficult healthcare conversations. Interventions aimed at anxiety management are particularly needed. PMID- 26277286 TI - Resilience and its influential factors in left-behind middle school students in Yunyang County of Rural Three Gorges Areas in China: a cross-sectional survey. AB - BACKGROUND: Left-behind middle school students are a common phenomenon in the rural Three Gorges areas causing wide concerns as students in puberty undergoing rapid development of the mind and body. This study examines the mental health of the left-behind middle school students from a positive perspective instead of emphasizing negative factors, which may explore a new way to study their mental health. STUDY DESIGN: A cross-sectional survey. METHODS: A cross-sectional study was conducted among middle school students in the Yunyang County of the Rural Three Gorges areas. Information about demographic characteristics was collected using a self-designed questionnaire; mental health status, resilience status, and the influential factors of resilience were collected using Mental Health Test (MHT) and Resilience and Youth Development Module (RYDM) scales. RESULTS: The detection rate of mental health problems in left-behind students was 6.01%. The difference in detection rates between left-behind students and non-left-behind students was not significant. The detection rates of low resilience in left behind students was 0.95%, of medium resilience was 54.15%, and of high resilience was 44.90%. Binary logistic regression analysis showed that influential factors associated with the resilience of left-behind students included grade, contradiction with the guardian, and students' worry about their parents working outside the county. CONCLUSIONS: Future studies should explore the links between each influential factor and its influencing mechanism. Meanwhile, the appropriate mental health education activities should be conducted in line with local conditions. PMID- 26277287 TI - Ambient fine particulate matter air pollution and leisure-time physical inactivity among US adults. AB - OBJECTIVES: There is mounting evidence documenting the adverse health effects of short- and long-term exposure to ambient fine particulate matter (PM2.5) air pollution, but population-based evidence linking PM2.5 and health behaviour remains lacking. This study examined the relationship between ambient PM2.5 air pollution and leisure-time physical inactivity among US adults 18 years of age and above. STUDY DESIGN: Retrospective data analysis. METHODS: Participant-level data (n = 2,381,292) from the Behavioral Risk Factor Surveillance System 2003 2011 surveys were linked with Wide-ranging Online Data for Epidemiologic Research air quality data by participants' residential county and interview month/year. Multilevel logistic regressions were performed to examine the effect of ambient PM2.5 air pollution on participants' leisure-time physical inactivity, accounting for various individual and county-level characteristics. Regressions were estimated on the overall sample and subsamples stratified by sex, age cohort, race/ethnicity and body weight status. RESULTS: One unit (MUg/m(3)) increase in county monthly average PM2.5 concentration was found to be associated with an increase in the odds of physical inactivity by 0.46% (95% confidence interval = 0.34%-0.59%). The effect was similar between the sexes but to some extent (although not always statistically significant) larger for younger adults, Hispanics, and overweight/obese individuals compared with older adults, non Hispanic whites or African Americans, and normal weight individuals, respectively. CONCLUSIONS: Ambient PM2.5 air pollution is found to be associated with a modest but measurable increase in individuals' leisure-time physical inactivity, and the relationship tends to differ across population subgroups. PMID- 26277288 TI - [Declaration of funding and funding sources received by research projects presented at the largest international nursing research conference]. PMID- 26277290 TI - Positive Fluid Balance Is Associated With Poor Outcomes in Subarachnoid Hemorrhage. AB - BACKGROUND: Strict maintenance of normovolemia is standard of care in the treatment of aneurysmal subarachnoid hemorrhage (aSAH), and induced hypervolemia is often used to treat delayed cerebral ischemia from vasospasm. We tested the hypothesis that positive fluid balance could adversely affect clinical outcomes in aSAH. METHODS: We reviewed 288 patients with aSAH admitted to the Neuroscience Intensive Care Unit (NICU) from October 2001 to June 2011. We collected data on fluid balance during NICU stay, clinical and radiographic evidence of vasospasm, cardiopulmonary complications, and functional outcomes by modified Rankin Scale (mRS) on follow-up (mean 8 +/- 8 months). Poor functional outcome was defined as an mRS score 3-6. Associations of variables of interest with outcome were assessed using univariable and multivariable logistic regression. Propensity scores were estimated to account for imbalances between patients with positive versus negative fluid balance and were included in multivariable models. RESULTS: Average net fluid balance during the NICU stay was greater in patients with poor functional outcome (3.52 +/- 5.51 L versus -.02 +/- 5.30 L in patients with good outcome; P < .001). On multivariate analysis, positive fluid balance (P = .002) was independently associated with poor functional outcome along with World Federation of Neurosurgical Societies grade (P < .001), transfusion (P = .003), maximum glucose (P = .005), and radiological evidence of cerebral infarction (P = .008). After regression adjustment with propensity scores, the association of positive fluid balance with poor functional outcome remained significant (odds ratio, 1.18; 95% confidence interval, 1.08-1.29; P < .001). CONCLUSIONS: Greater positive net fluid balance is independently associated with poorer functional outcome in patients with aSAH. PMID- 26277291 TI - Japanese Adaptation of the Stroke and Aphasia Quality of Life Scale-39 (SAQOL 39): Comparative Study among Different Types of Aphasia. AB - BACKGROUND: We have developed a Japanese version of the Stroke and Aphasia Quality of Life Scale-39 (SAQOL-39), designated as SAQOL-39-J, and used psychometric methods to examine its acceptability and reliability. METHODS: The acceptability and reliability of SAQOL-39-J, which was developed from the English version using a standard translation and back-translation method, were examined in 54 aphasia patients using standard psychometric methods. The acceptability and reliability of SAQOL-39-J were then compared among patients with different types of aphasia. RESULTS: SAQOL-39-J showed good acceptability, internal consistency (Cronbach's alpha score = .90), and test-retest reliability (intraclass correlation coefficient = .97). Broca's aphasia patients showed the lowest total scores and communication scores on SAQOL-39-J. CONCLUSIONS: The Japanese version of SAQOL-39, SAQOL-39-J, provides acceptable and reliable data in Japanese stroke patients with aphasia. Among different types of aphasia, Broca's aphasia patients had the lowest total and communication SAQOL-39-J scores. Further studies are needed to assess the effectiveness of health care interventions on health-related quality of life in this population. PMID- 26277292 TI - Acute Posterior Multifocal Placoid Pigment Epitheliopathy Associated with Stroke: A Case Report and Review of the Literature. AB - BACKGROUND: Present a case report of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) associated with stroke along with the serologic findings, diagnostic findings, and treatment in addition to presenting a review of other case reports to date in literature. With this information, we are attempting to identify key diagnostic features and appropriate treatment options for patients with this disease. METHODS: Presentation of case report, background on APMPPE, review of the literature and previous case reports, and discussion of diagnostic workup and treatment options for these patients. RESULTS: There are 28 well described case reports in the literature to date, not including our case report; 23 had documented radiographic findings consistent with parenchymal injury, ischemic stroke, hemorrhagic stroke, or cerebral venous thrombosis. We report a 23-year-old right-handed man with left hemiparesis, ischemic strokes, and angiographic findings characteristic of cerebral vasculitis 4 months after he was diagnosed with APMPPE. CONCLUSIONS: Based on our present case and previously documented cases to date, corticosteroid therapy with potential escalation of care to immunomodulatory treatment appears to benefit clinical outcomes. PMID- 26277289 TI - Biomimetic particles as therapeutics. AB - In recent years, there have been major advances in the development of novel nanoparticle- and microparticle-based therapeutics. An emerging paradigm is the incorporation of biomimetic features into these synthetic therapeutic constructs to enable them to better interface with biological systems. Through the control of size, shape, and material consistency, particle cores have been generated that better mimic natural cells and viruses. In addition, there have been significant advances in biomimetic surface functionalization of particles through the integration of bio-inspired artificial cell membranes and naturally derived cell membranes. Biomimetic technologies enable therapeutic particles to have increased potency to benefit human health. PMID- 26277293 TI - Conventional Computed Tomography and Axial Magnetic Resonance T2-Weighted Imaging of Horizontal Segment of Middle Cerebral Artery in Moyamoya Disease or Syndrome in Adult Patients. AB - BACKGROUND: Moyamoya disease or syndrome (MMD or MMS) is a cerebrovascular disease characterized by stenosis or occlusion of the distal portion of the internal carotid arteries, with ultimate spread to the proximal portion of the anterior cerebral arteries and middle cerebral arteries (MCAs). In the present study, we wanted to evaluate the usefulness of conventional computed tomography (CT) and axial magnetic resonance (MR) T2-weighted imaging (T2WI) for the examination of horizontal segments of the MCAs (ie, M1 segments) in patients diagnosed with MMD or MMS. METHODS: This study enrolled 29 patients (n = 11 men; n = 18 women), who underwent conventional CT and/or MR T2WI. CT angiography, MR angiography, or digital subtraction angiography was used as a reference. CT and MR imaging data were reviewed by 2 experienced radiologists, who analyzed and recorded stenosis or occlusions of the M1 segments. We performed statistical analyses to compare the diagnostic accuracy of both techniques on M1 segments in MMD or MMS. RESULTS: Fifty-three steno-occlusive changes of M1 segments were revealed by angiography in the 29 patients. T2W-MRI allowed the identification of moyamoya vessels with 100% success rate. Stenosis and occlusion of M1 segments were better visualized on axial T2W-MRI compared to conventional CT (94.59% versus 71.43%; P = .008). CONCLUSIONS: Our study showed that conventional CT and axial T2W-MRI could be used to identify the steno-occlusive changes of the horizontal segment of the MCA in MMD or MMS, which may have a significant impact on the accurate diagnosis of this disease at its early stage. PMID- 26277294 TI - International Comparison of Poststroke Resource Use: A Longitudinal Analysis in Europe. AB - BACKGROUND: Long-term costs often represent a large proportion of the total costs induced by stroke, but data on long-term poststroke resource use are sparse, especially regarding the trajectory of costs by severity. We used a multinational longitudinal survey to estimate patterns of poststroke resource use by degree of functional disability and to compare resource use between regions. METHODS: The Survey of Health, Ageing and Retirement in Europe (SHARE) is a multinational database of adults 50 years and older, which includes demographic information about respondents, age when stroke first occurred, current activity of daily living (ADL) limitations, and health care resource use in the year before interview. We modeled resource use with a 2-part regression for number of hospital days, home nursing hours, and paid and unpaid home caregiving hours. RESULTS: After accounting for time since stroke, number of strokes and comorbidities, age, gender, and European regions, we found that poststroke resource use was strongly associated with ADL limitations. The duration since the stroke event was significantly associated only with inpatient care, and informal help showed significant regional heterogeneity across all ADL limitation levels. CONCLUSIONS: Poststroke physical deficits appear to be a strong driver of long term resource utilization; treatments that decrease such deficits offer substantial potential for downline cost savings. Analyzing internationally comparable panel data, such as SHARE, provide valuable insight into long-term cost of stroke. More comprehensive international comparisons will require registries with follow-up, particularly for informal and formal home-based care. PMID- 26277295 TI - Effect of Diltiazem on Coronary Artery Flow and Myocardial Perfusion in Patients With Isolated Coronary Artery Ectasia and Either Stable Angina Pectoris or Positive Myocardial Ischemic Stress Test. AB - Isolated coronary artery ectasia (CAE) may be associated with stable or unstable coronary events despite the absence of epicardial coronary stenosis. Impaired coronary flow dynamics and myocardial perfusion have been demonstrated in stable patients with ectatic coronary arteries. We aimed to assess whether epicardial flow and tissue-level perfusion would be improved by diltiazem in myocardial regions subtended by the ectatic coronary arteries in patients with isolated CAE. A total of 60 patients with isolated CAE were identified of 9,780 patients who underwent elective coronary angiography. Patients were randomized to 5 mg of intracoronary diltiazem or saline. Coronary blood flow of the microvascular network was assessed using myocardial blush grade (MBG) technique. The thrombolysis in myocardial infarction (TIMI) flow grade and TIMI frame count (TFC) were used to assess epicardial coronary flow. MBG (from 2.4 to 2.6, p = 0.02), TIMI flow grades (from 2.4 to 2.8, p <0.001), and TFC (from 35 to 26, p <0.001) were significantly improved after diltiazem, whereas no significant change was noticed after saline (from 2.4 to 2.4, p = 0.86 for MBG; from 2.3 to 2.3, p = 0.71 for TIMI flow grade; and from 35 to 33, p = 0.43 for TFC). Diltiazem provided amelioration of the altered coronary flow dynamics, which was suggested as the pathophysiological influence of CAE. In conclusion, the favorable effects of the diltiazem on myocardial perfusion were observed at both epicardial and tissue levels. PMID- 26277296 TI - Self-Inserted Needles in the Heart. AB - Cardiac injuries due to penetration by sharp foreign bodies usually have a clear clinical presentation. A case of a 38-year-old man with self-inserted cardiac lesions and a misleading presentation is reported. The patient was admitted to the emergency room because of chest pain, with increase in biomarkers of myocardial necrosis, and electrocardiographic and echocardiographic abnormalities inducing initial diagnostic and therapeutic workup of acute coronary syndrome. Once clinical destabilization followed by death had occurred, the suspicion of an alternative diagnosis came from delayed chest radiography, confirmed by autopsy, revealing the presence of multiple metallic objects within the thorax. PMID- 26277297 TI - "Jackhammer esophagus" and eosinophilic esophagitis. PMID- 26277298 TI - Proteomic analysis of Vibrio metschnikovii under cold stress using a quadrupole Orbitrap mass spectrometer. AB - Vibrio metschnikovii is a food-borne pathogen found in seafood worldwide. We studied the global proteome responses of V. metschnikovii under cold stress by nano-flow ultra-high-performance liquid chromatography coupled to a quadrupole Orbitrap mass spectrometer. A total of 2066 proteins were identified, among which 288 were significantly upregulated and 572 were downregulated. Functional categorization of these proteins revealed distinct differences between cold stressed and control cells. Quantitative reverse transcription polymerase chain reaction analysis was also performed to determine the mRNA expression levels of seventeen cold stress-related genes. The results of this study should improve our understanding of the metabolic activities of cold-adapted bacteria and will facilitate a better systems-based understanding of V. metschnikovii. PMID- 26277299 TI - Screening for Elder Abuse in Healthcare Settings: Why Should We Care, and Is It a Missed Quality Indicator? PMID- 26277300 TI - Genetics of Canine Primary Glaucomas. AB - Primary glaucomas are a leading cause of incurable vision loss in dogs. Based on their specific breed predilection, a genetic cause is suspected to be responsible, and affected dogs should be excluded from breeding. Despite the high prevalence of primary glaucomas in dogs, their genetics have been studied in only a small number of breeds. The identification of canine glaucoma disease genes, and the development of genetic tests, will help to avoid the breeding of affected dogs in the future and will allow for earlier diagnosis and potentially more effective therapy. PMID- 26277301 TI - Reply to Thorsten Derlin, Matthias Eiber, Markus Schwaiger, and Frank M. Bengel's Letter to the Editor re: Lars Budaus, Sami-Ramzi Leyh-Bannurah, Georg Salomon, et al. Initial Experience of (68)Ga-PSMA PET/CT Imaging in High-risk Prostate Cancer Patients Prior to Radical Prostatectomy. Eur Urol 2016;69:393-6. PMID- 26277302 TI - The Devil is in the Details: Still True. PMID- 26277303 TI - Nerve-sparing Surgery Technique, Not the Preservation of the Neurovascular Bundles, Leads to Improved Long-term Continence Rates After Radical Prostatectomy. AB - BACKGROUND: The effect of preservation of neurovascular bundles (NVBs) during radical prostatectomy (RP) on continence remains controversial. OBJECTIVE: To analyze if the differing surgical techniques of nerve-sparing (NS) versus non nerve-sparing (NNS) RP and not the preservation of the NVB itself may be responsible for differences in continence rates. DESIGN, SETTING, AND PARTICIPANTS: A total of 18 427 men who underwent RP from 2002 to 2014 in a single high-volume center were analyzed retrospectively. Patients with bilateral NS RP, with primary NNS RP, and with bilateral secondary resection of the NVBs for positive frozen-section results after an initial bilateral nerve sparing (secNNS) RP were studied. INTERVENTION: NS, NNS, or secNNS RP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable and propensity score matched analyses adjusting for age, prostate volume, and year of surgery were performed to assess differences in continence rates after RP. Continence was defined as the use of no or one safety pad per day. RESULTS AND LIMITATIONS: Post-RP urinary continence rates at 1 wk, 3 mo, and 12 mo were 59.8%, 76.2%, 85.4% in the NS group, 39.5%, 59.5%, and 87.0% in the secNNS group, and 29.1%, 52.8%, and 70.5% in the NNS group. Continence rates at 12 mo after surgery did not differ significantly between patients who had bilateral NS and patients who had resection of both NVBs after an initial nerve-sparing technique (secNNS). In contrast, when comparing the NNS study groups with initial NNS versus secNNS, the latter group had significantly higher continence rates after 12 mo. CONCLUSIONS: Our results indicate that the meticulous apical dissection associated with the NS RP technique rather than the preservation of the NVBs itself may have a positive impact on long-term urinary continence rates. PATIENT SUMMARY: We looked at continence rates after nerve-sparing (NS) versus non-NS radical prostatectomy (RP). NS surgery technique but not the preservation of the neurovascular bundles led to improved long-term continence rates after RP. PMID- 26277304 TI - On the local Mousterian origin of the Chatelperronian: Integrating typo technological, chronostratigraphic and contextual data. AB - Across Europe the period 45-40 ka (thousands of years ago) is associated with several technological changes, including the emergence of the Chatelperronian technocomplex in France and northern Spain. The Chatelperronian, stratigraphically located between the Mousterian and Aurignacian, is characterized by Upper Palaeolithic features, such as volumetric blade reduction, curved backed blades, end-scrapers, bladelets, bone tools and ornaments. Concurrently, repeated, though debated, associations with Neanderthal remains and Mousterian elements suggest a local technological development. Following recent critiques and cumulating technological studies, this paper provides data-driven contextualisations of the Chatelperronian and late Mousterian archaeological records and a primary comparative assessment of a major linking element, backed knives, to re-assess the origin of the Chatelperronian. The results demonstrate the challenging nature of the 50-35 ka record, with many interpretive problems caused by poorly recorded excavations, resulting in only 25 well-contextualised assemblages from the claimed 143 Chatelperronian find spots. These 25 assemblages facilitate more detailed chronostratigraphic and typo-technological assessments and show that the Chatelperronian has a homogenous set of technologies and tools. A similar evaluation of the late Mousterian indicates a wide-ranging late Neanderthal skill set, commonly including laminar blank production and backing. Further, conceptual similarities were noted both in blank selection and edge modification between Mousterian and Chatelperronian backed knives, alongside their near-absence in other, contemporaneous technocomplexes. A Europe-wide contextualisation shows that while the current coarse-grained record still allows for several potential scenarios, the data throughout this paper point towards a most parsimonious model of a Chatelperronian made by Neanderthals, with roots in the late Middle Palaeolithic technological skill set. However, this change seems triggered by early arrivals of modern humans either indirectly, through stimulus diffusion, or directly, after ca. 42 ka. Fully testing this model requires an ongoing focus on site formation and assemblage integrity, alongside in-depth analyses of recently excavated assemblages and existing collections. PMID- 26277305 TI - Taphonomy of fossils from the hominin-bearing deposits at Dikika, Ethiopia. AB - Two fossil specimens from the DIK-55 locality in the Hadar Formation at Dikika, Ethiopia, are contemporaneous with the earliest documented stone tools, and they collectively bear twelve marks interpreted to be characteristic of stone tool butchery damage. An alternative interpretation of the marks has been that they were caused by trampling animals and do not provide evidence of stone tool use or large ungulate exploitation by Australopithecus-grade hominins. Thus, resolving which agents created marks on fossils in deposits from Dikika is an essential step in understanding the ecological and taphonomic contexts of the hominin bearing deposits in this region and establishing their relevance for investigations of the earliest stone tool use. This paper presents results of microscopic scrutiny of all non-hominin fossils collected from the Hadar Formation at Dikika, including additional fossils from DIK-55, and describes in detail seven assemblages from sieved surface sediment samples. The study is the first taphonomic description of Pliocene fossil assemblages from open-air deposits in Africa that were collected without using only methods that emphasize the selective retention of taxonomically-informative specimens. The sieved assemblages show distinctive differences in faunal representation and taphonomic modifications that suggest they sample a range of depositional environments in the Pliocene Hadar Lake Basin, and have implications for how landscape-based taphonomy can be used to infer past microhabitats. The surface modification data show that no marks on any other fossils resemble in size or shape those on the two specimens from DIK-55 that were interpreted to bear stone tool inflicted damage. A large sample of marks from the sieved collections has characteristics that match modern trampling damage, but these marks are significantly smaller than those on the DIK-55 specimens and have different suites of characteristics. Most are not visible without magnification. The data show that the DIK-55 marks are outliers amongst bone surface damage in the Dikika area, and that trampling is not the most parsimonious interpretation of their origin. PMID- 26277306 TI - Influence of Plio-Pleistocene basin hydrology on the Turkana hominin enamel carbonate delta(18)O values. AB - Stable oxygen isotopes of hominin enamel carbonate (delta(18)OEC) provide a window into aspects of past drinking behavior and diet, body size, breastfeeding and weaning, mobility, and paleoclimate. It is tempting to compare all hominins across time and space in order to gauge species-level adaptations to changing environments and niche separation between those living sympatrically. Basinal, sub-basinal, and micro-environmental differences, however, may exert an influence on variation in enamel carbonate isotopic values that must be reconciled before hominin species across Africa can be meaningfully compared. Plio-Pleistocene Turkana hominin delta(18)OEC values show a considerable spread, potentially revealing many intrinsic and extrinsic contributing factors operating on different scales. In this study, I examine Turkana hominin delta(18)OEC values relative to identity (taxon, tooth type and number, body size of taxon), dietary (delta(13)C value, Turkana coeval and modern mammalian delta(18)OEC values), and contextual (time, depositional environment) information of each specimen and collection locality and discuss various potential influences. Turkana hominin delta(18)OEC values may primarily reflect differences in imbibed water sources (lake vs. river) as a function of evolving basin hydrology. PMID- 26277307 TI - The rapid increase of circulating adiponectin in neonatal calves depends on colostrum intake. AB - Adiponectin, an adipokine, regulates metabolism and insulin sensitivity. Considering that the transplacental transfer of maternal proteins of high molecular weight is hindered in ruminants, this study tested the hypothesis that the blood concentration of adiponectin in neonatal calves largely reflects their endogenous synthesis whereby the intake of colostrum might modify the circulating concentrations. We thus characterized the adiponectin concentrations in neonatal and young calves that were fed either colostrum or formula. Three trials were performed: in trial 1, 20 calves were all fed colostrum for 3 d, and then formula until weaning. Blood samples were collected on d 0 (before colostrum feeding), and on d 1, 3, 11, 22, 34, 43, 52, 70, 90, and 108 postnatum. In trial 2, 14 calves were studied for the first 4 d of life. They were fed colostrum (n=7) or formula (n=7), and blood samples were taken right after birth and before each morning feeding on d 2, 3, and 4. In trial 3, calves born preterm (n=7) or at term received colostrum only at 24 h postnatum. Blood was sampled at birth, and before and 2 h after feeding. Additionally, allantoic fluid and blood from 4 Holstein cows undergoing cesarean section were sampled. Adiponectin was quantified by ELISA. In trial 1, the serum adiponectin concentrations recorded on d 3 were 4.7-fold higher than before colostrum intake. The distribution of the molecular weight forms of adiponectin differed before and after colostrum consumption. In trial 2, the colostrum group had consistently greater plasma adiponectin concentrations than the formula group after the first meal. In trial 3, the preterm calves tended to have lower concentrations of plasma adiponectin than the term calves at birth and before and 2 h after feeding. Furthermore, the adiponectin concentrations were substantially lower in allantoic fluid than in the sera from neonatal calves and from cows at parturition. Our results show that calves are born with very low blood concentrations of adiponectin and placental transfer of adiponectin to the bovine fetus is unlikely. In conclusion, colostrum intake is essential for the postnatal increase of circulating adiponectin in newborn calves. PMID- 26277308 TI - Inclusion of various amounts of steam-flaked soybeans in lactating dairy cattle diets. AB - Whereas most soybean feedstuffs have been extensively investigated for use in ruminant diets, a lack of information exists regarding steam-flaked soybeans (SFSB). This research evaluated various inclusion rates of SFSB in diets for lactating dairy cattle. Twelve multiparous Holstein cows (103 +/- 39 d in milk) were used in a 4 * 4 Latin square experiment consisting of 28-d periods, 14 d for diet transitioning followed by a 14-d sampling period. Treatments were inclusion of SFSB at 0, 5, 10, and 15% of dietary dry matter (DM), replacing a mixture of soybean meal, soy hulls, calcium salts of fatty acids, and choice white grease. Animals were fed lactating dairy cow diets formulated to be isonitrogenous and isoenergetic, containing 60% of DM as forage and 40% of DM as concentrate. Dry matter intake (mean = 28.8 kg/d), milk production (42.2 kg/d), milk fat percentage (3.52%), and feed efficiency (1.43 kg of energy-corrected milk/kg of DM intake) were similar across all treatments. Milk protein (2.98%) and lactose (4.87%) were also unaffected by the amount of SFSB in the diet. Milk urea nitrogen concentration decreased linearly as the amount of SFSB in the diet increased. Unlike some other soybean supplements, feeding SFSB did not increase trans-11 C18:1 or cis-9,trans-11 conjugated linoleic acid, but instead resulted in increased cis-9,cis-12 C18:2 and alpha-C18:3. Body weights (752 kg) and body condition scores (3.17) were similar with all diets. This research demonstrated that SFSB can be substituted for soybean meal and commercial fat sources while maintaining milk and milk component production and decrease milk urea nitrogen concentration. PMID- 26277309 TI - Short communication: Genetic relationships between functional longevity and direct health traits in Austrian Fleckvieh cattle. AB - The aim of this study was to conduct a multitrait 2-step approach applied to yield deviations and deregressed breeding values to get genetic parameters of functional longevity, clinical mastitis, early fertility disorders, cystic ovaries, and milk fever of Austrian Fleckvieh cattle. An approximate multitrait approach allows the combination of information from pseudo-phenotypes derived from different statistical models in routine genetic evaluation, which cannot be estimated easily in a full multitrait model. A total of 66,890 Fleckvieh cows were included in this study. For estimating genetic parameters, a simple linear animal model with year of birth as a fixed effect and animal as a random genetic effect was fitted. The joint analysis of yield deviations and deregressed breeding values was feasible. As expected, heritabilities were low, ranging from 0.03 (early fertility disorders) to 0.15 (functional longevity). Genetic correlations between functional longevity and clinical mastitis, early fertility disorders, cystic ovaries, and milk fever were 0.63, 0.29, 0.20, and 0.20, respectively. Within direct health traits genetic correlations were between 0.14 and 0.45. Results suggest that selecting for more robust disease-resistant cows would imply an improvement of functional longevity. PMID- 26277310 TI - Short communication: Characterizing metabolic and oxidant status of pastured dairy cows postpartum in an automatic milking system. AB - The periparturient period represents a stressful time for dairy cows as they transition from late gestation to early lactation. Undesirable fluctuations in metabolites and impaired immune defense mechanisms near parturition can severely affect cow health and have residual effects on performance and longevity. Metabolic and oxidative stress profiles of multiparous and primiparous dairy cows in traditional parlor and feeding systems are well characterized, but status of these profiles in alternative management systems, such as grazing cows managed with an automatic milking system (AMS), are poorly characterized. Therefore, the objective of this case study was to characterize the metabolic and oxidant status of pastured cows milked with an AMS. It was hypothesized that primiparous and multiparous cows milked with an AMS would experience changes in oxidative and metabolic status after parturition; however, these changes would not impair cow health or production. Blood was collected from 14 multiparous and 8 primiparous Friesian-cross dairy cows at 1, 7, 14, and 21 d relative to calving for concentrations of insulin, glucose, nonesterified fatty acids (NEFA), beta hydroxybutyrate, reduced glutathione, oxidized glutathione, and antioxidant potential. Milk production and milking frequency data were collected postpartum. Milk production differed on d 7 and 14 between primiparous and multiparous cows and frequency was not affected by parity. Primiparous cows had higher levels of glucose than multiparous cows. No differences in insulin, NEFA, or beta hydroxybutyrate concentrations were noted between multiparous and primiparous cows postpartum, though days relative to calving significantly affected insulin and NEFA. Primiparous cows also had higher antioxidant potential than multiparous cows during the postpartum period. Results from this study show that, although responses were within expected ranges, periparturient multiparous cows responded differently than periparturient primiparous cows with respect to metabolic and oxidative measures during the postpartum period at this pastured-AMS dairy, suggesting different management strategies may need to be considered with primiparous and multiparous cows. PMID- 26277311 TI - Influence of ensiling, exogenous protease addition, and bacterial inoculation on fermentation profile, nitrogen fractions, and ruminal in vitro starch digestibility in rehydrated and high-moisture corn. AB - Exogenous protease addition may be an option to increase proteolysis of zein proteins and thus starch digestibility in rehydrated and high-moisture corn (HMC) ensiled for short periods. In addition, microbial inoculation may accelerate fermentation and increase acid production and thus increase solubilization of zein proteins. Four experiments were performed to evaluate the effect on fermentation profile, N fractions, and ruminal in vitro starch digestibility (ivSD) of the following: (1) rehydration and ensiling of dry ground corn; (2) exogenous protease addition to rehydrated un-ensiled and ensiled corn; (3) exogenous protease addition or inoculation in rehydrated ensiled corn; and (4) exogenous protease addition or inoculation in HMC. Experiments 1, 2, and 3 were performed with 7 treatments: dry ground corn (DGC); DGC rehydrated to a targeted dry matter content of 70% (REH); REH treated with exogenous protease (REH+); REH ensiled for 30 d (ENS); ENS treated with exogenous protease (ENS+); ENS treated with a microbial inoculant containing Lactobacillus plantarum, Lactobacillus casei, Enterococcus faecium, and Pediococcus sp. (ENSI); and ENS treated with exogenous protease and microbial inoculant (ENSI+). Experiment 1 compared DGC, REH, and ENS with ivSD being greater for ENS (64.9%) than DGC and REH (51.7% on average). Experiment 2 compared REH and ENS without or with exogenous protease addition (REH+ and ENS+, respectively). Ensiling and exogenous protease addition increased ivSD, but exogenous protease addition was more effective in ENS than REH (6.4 vs. 2.6 percentage unit increase). Experiment 3 compared the effects of exogenous protease addition and inoculation in ENS corn (ENS, ENS+, ENSI, and ENSI+). The addition of protease, but not inoculant, increased ivSD. Inoculation reduced pH and acetate, propionate, and ethanol concentrations, and increased lactate and total acid concentrations. In experiment 4, 8 treatments were a combination of HMC noninoculated or inoculated with 1 of 3 microbial inoculants and with or without exogenous protease addition. The inoculant treatments contained (1) Lactobacillus buchneri 40788 and Pediococcus pentosaceus, (2) L. buchneri 40788, and (3) a mixture of P. pentosaceus and Propionibacterium freudenreichii. Protease, but not inoculation, increased ivSD by 7.5 percentage units (44.4 vs. 51.9%). Protease addition increased ivSD in rehydrated corn and HMC. Microbial inoculation improved fermentation profiles but did not affect ivSD. PMID- 26277312 TI - Short communication: The effects of cabergoline administration at dry-off of lactating cows on udder engorgement, milk leakages, and lying behavior. AB - Cabergoline is an ergot derivative with high affinity for the D2 dopamine receptors whose dopaminergic effects cause inhibition of prolactin (PRL) secretion; thus, it could be considered a molecule that acts as a potential dry off facilitator. One hundred ninety-nine Holstein cows (102 primiparous; 97 multiparous) producing >= 18 kg/d at dry-off were split in 2 treatments to evaluate the effects of diminishing PRL secretion at dry-off (between 70 and 50 d from the expecting calving date) on udder engorgement, milk leakage, and cow well being after dry-off. Treatments consisted of a single i.m. injection of 5 mL of a solution containing 5.6 mg of cabergoline (CAB; Velactis, Ceva Sante Animal, Libourne, France) or 5 mL of saline solution as a placebo (CTRL). Each animal was evaluated for presence or absence of milk leakages during the 4 d following dry off and udder engorgement was determined using a digital algometer. Lying behavior was recorded during 10 d after dry-off. Twenty-five cows from each treatment were randomly chosen and blood sampled at 3 and 15 d after dry-off, and again at 5 and 3 d before the expected calving date to determine serum PRL concentrations. Cows on CAB had lower serum PRL concentrations than cows on CTRL at 3 and 15 d after dry-off. Average udder engorgement was lower for cows on CAB than for cows on CTRL following dry-off, and it decreased as days after dry-off increased. The overall incidence of milk leakage in cows on CAB (3.1 +/- 0.88%) was 73.5% of that obtained in cows on CTRL (11.7 +/- 1.64%); cows on CAB had 0.2 lower odds of incurring milk leakage than cows on CTRL. The day following dry off, CAB cows lied about 1.5h/d more than cows on CTRL. We conclude that i.m. administration of 5.6 mg of cabergoline at dry-off effectively reduces PRL secretion, udder engorgement, and milk leakages, and improves lying time the day following dry-off. PMID- 26277313 TI - Bacterial species and their associations with acute and chronic mastitis in suckler ewes. AB - Acute mastitis in suckler ewes is often detected because of systemic signs such as anorexia or lameness, whereas chronic mastitis, characterized by intramammary abscesses with no systemic disease, is typically detected when ewes are inspected before mating. The aims of the current study were to identify the species and strains of culturable bacteria associated with acutely diseased, chronically diseased, and unaffected mammary glands to investigate whether species and strains vary by state. To investigate acute mastitis, 28 milk samples were obtained from both glands of 14 ewes with acute mastitis in one gland only. To investigate chronic mastitis, 16 ovine udders were obtained from 2 abattoirs; milk was aspirated from the 32 glands where possible, and the udders were sectioned to expose intramammary abscesses, which were swab sampled. All milk and swab samples were cultured aerobically. In total, 37 bacterial species were identified, 4 from acute mastitis, 26 from chronic mastitis, and 8 from apparently healthy glands. In chronic mastitis, the overall coincidence index of overlap of species detected in intramammary abscesses and milk was 0.60, reducing to 0.36 within individual glands, indicating a high degree of species overlap in milk and abscesses overall, but less overlap within specific glands. Staphylococcus aureus was detected frequently in all sample types; it was isolated from 10/14 glands with acute mastitis. In 5 ewes, closely related strains were present in both affected and unaffected glands. In chronic mastitis, closely related Staphylococcus aureus strains were detected in milk and abscesses from the same gland. PMID- 26277314 TI - Improvement of skin condition by oral supplementation with sphingomyelin containing milk phospholipids in a double-blind, placebo-controlled, randomized trial. AB - Sphingomyelin (SM), an essential phospholipid for the skin, is contained largely in the milk fat globule membrane surrounding milk fat, concentrated fractions of which are also generated concurrently during the manufacture of dairy products. Such an SM-containing milk phospholipid concentrate (SM-MPC) is useful for investigating the benefits of dietary SM. Here, we examined the effect of consuming SM-MPC on the condition of skin in a double-blind, placebo-controlled, randomized trial. Ninety-six healthy subjects aged 20 to 39 yr with low skin hydration were randomly assigned to 3 groups: a high-SM group supplemented with SM-MPC at a dose equivalent to 10 mg/d of SM, a low-SM group supplemented with SM MPC equivalent to 5 mg/d of SM, and a placebo group fed a vehicle composed of olive oil and beeswax. During daily supplementation for 12 wk, parameters related to the condition of skin were evaluated at baseline and every 3 wk. Skin hydration at the heel was significantly increased at wk 9 and 12 in the low-SM group compared with the placebo group. Skin elasticity in the region below the eye was significantly increased at wk 9 in the high-SM group versus placebo. Questionnaire-based subjective perceptions of skin conditions were significantly improved for facial skin moisture at wk 3 and 12, and in the wrinkle around the eyes at wk 9 and 12 in the high-SM group versus placebo. Our results indicate that constant and long-term supplementation with SM-MPC is capable of improving the general condition of skin. PMID- 26277315 TI - Formation of volatile compounds in kefir made of goat and sheep milk with high polyunsaturated fatty acid content. AB - This article explored the formation of volatile compounds during the production of kefir from goat and sheep milks with high polyunsaturated fatty acids (PUFA) as a result of feeding animals forage supplemented with maize dried distillers grains with solubles (DDGS). The increased PUFA content of the goat and sheep milks resulted in significant changes to the fermentation process. In particular, apart from an increase in the time taken to ferment sheep milk, fermentation yielded less 2,3-butanedione. The highest quantities of this compound were assayed in kefir produced from goat milk with an increased content of PUFA. An increase of PUFA significantly elevated ethanal synthesis during lactose-alcohol fermentation of sheep milk. Neither the origin of milk (sheep or goat) nor the level of PUFA had any statistical effect on the amount of ethanal assayed during the fermentation of milk and within the finished product. The proportion of l(+) lactic acid was higher in kefirs produced using goat milk compared with sheep milk and did not depend on the content of PUFA in milk fat. The content of PUFA had a significant effect on the aroma profile of the resulting kefirs. An increase in PUFA content resulted in the loss of whey aroma in goat milk kefirs and the animal odor in sheep milk kefirs, and a creamy aroma became more prevalent in kefirs made from sheep milk. PMID- 26277316 TI - Low-sodium Cheddar cheese: Effect of fortification of cheese milk with ultrafiltration retentate and high-hydrostatic pressure treatment of cheese. AB - Low-sodium cheeses often exhibit an acidic flavor due to excessive acid production during the manufacturing and the initial stage of ripening, which is caused by ongoing starter culture activity facilitated by the low salt-in moisture levels. We proposed that this excessive starter-induced acidity could be prevented by the fortification of cheese milk with ultrafiltration (UF) retentates (to increase curd buffering), and by decreasing microbial activity using the application of high-hydrostatic pressure (HHP) treatment (that is, to reduce residual starter numbers). Camel chymosin was also used as a coagulant to help reduce bitterness development (a common defect in low-sodium cheeses). Three types of low-Na (0.8% NaCl) Cheddar cheeses were manufactured: non-UF fortified, no HHP applied (L-Na); UF-fortified (cheese milk total solids = 17.2 +/- 0.6%), no HHP applied (L-Na-UF); and UF-fortified, HHP-treated (L-Na-UF-HHP; 500 MPa for 3 min applied at 1 d post-cheese manufacture). Regular salt (2% NaCl) non-UF fortified, non-HHP treated (R-Na) cheese was also manufactured for comparison purposes. Analysis was performed at 4 d, 2 wk, and 1, 3, and 6 mo after cheese manufacture. Cheese functionality during ripening was assessed using texture profile analysis and dynamic low-amplitude oscillatory rheology. Sensory Spectrum and quantitative descriptive analysis was conducted with 9 trained panelists to evaluate texture and flavor attributes using a 15-point scale. At 4 d and 2 wk of ripening, L-Na-UF-HHP cheese had ~2 and ~4.5 log lower starter culture numbers, respectively, than all other cheeses. Retentate fortification of cheese milk and HHP treatment resulted in low-Na cheeses having similar insoluble calcium concentrations and pH values compared with R-Na cheese during ripening. The L-Na UF cheese exhibited significantly higher hardness values (measured by texture profile analysis) compared with L-Na cheese until 1 mo of ripening; however, after 1 mo, all low-Na cheeses exhibited similar hardness values, which were significantly lower than R-Na cheese. Pressure treatment significantly increased maximum loss tangent (meltability) from rheology testing and decreased melt temperature. Sensory results indicated only very slight bitterness (<2.5 out of 15-point scale) was detected in all cheeses during the 6 mo of ripening. The L-Na UF-HHP cheese did not significantly differ in bitterness and acidity from R-Na cheese during ripening. Pressures treatment of cheese at 500 MPa and cheese milk retentate fortification could be used to improve the quality of low-Na cheese. PMID- 26277317 TI - Conjugated linoleic acid isomers strongly improve the redox status of bovine mammary epithelial cells (BME-UV1). AB - Some studies have shown the protective effects of conjugated linoleic acid (CLA) isomers against oxidative stress and lipid peroxidation in animal models, but no information is available about CLA and changes in oxidative status of the bovine mammary gland. The objectives of the study were to assess in vitro the effect of CLA on the cellular antioxidant response of bovine mammary cells, to examine whether CLA isomers could play a role in cell protection against the oxidative stress, and to study the molecular mechanism involved. For the study, BME-UV1 cells, a bovine mammary epithelial cell line, were used as the experimental model. The BME-UV1 cells were treated with complete medium containing 50 uM cis 9,trans-11 CLA (c9,t11 CLA), trans-10,cis-12 CLA (t10,c12 CLA), and CLA mixture (1:1, cis-9,trans-11: trans-10,cis-12 CLA). To monitor cellular uptake of CLA isomers, cells and culture medium were collected at 0, 3, and 48 h from CLA addition for lipid extraction and fatty acid analyses. To assess the cellular antioxidant response, glutathione (GSH/GSSH), NADPH, and gamma-glutamyl-cysteine ligase activity was measured after 48 h from addition of CLA. Cytoplasmic superoxide dismutase, glutathione peroxidase, glutathione S-transferase, and glutathione reductase activities and mRNA were also determined. Intracellular reactive oxygen species and thiobarbituric acid reactive substance production were assessed in cells supplemented with CLA isomers. Cell viability after 3h to H2O2 exposure was assessed to evaluate and to compare the potential protection of different CLA isomers against H2O2-induced oxidative stress. Mammary cells readily picked up all CLA isomers, their accumulation was time dependent, and main metabolites at 48 h are two 18:3 isomers. The CLA treatment induced an intracellular GSH increase, matched by high concentration of NADPH, and an increase of gamma-glutamyl-cysteine ligase activity mainly in cells treated with the t10,c12 CLA isomer. The CLA isomer treatment of bovine mammary cells increased superoxide dismutase, glutathione peroxidase, and glutathione S transferase activity and decreased glutathione reductase activity, but no changes in gene expression of these antioxidant enzymes were observed. Cells supplemented with CLA isomers showed a reduction in intracellular reactive oxygen species and thiobarbituric acid reactive substance levels. All CLA isomers were able to enhance cell resistance against H2O2-induced oxidative stress. These suggest an antioxidant role of CLA, in particular of t10,c12 CLA, by developing a significantly high redox status in cells. PMID- 26277318 TI - Rumen fermentation, blood metabolites, and growth performance of calves during transition from liquid to solid feed: Effects of dietary level and particle size of alfalfa hay. AB - This study evaluated the effects of particle size (PS) and dietary level of alfalfa hay (AH) on rumen fermentation parameters, blood metabolites, eating behavior, and growth performance in dairy calves during transition from liquid to solid feed. Sixty newborn dairy calves (41 +/- 2.5,kg of body weight) were used in a 2 * 2 factorial arrangement with the factors dietary AH level (medium, 12.5%, or high, 25%, on DM basis) and PS (fine = 1mm or medium = 3mm, as geometric means) of AH. Hence, the dietary treatments were (1) medium level of AH with fine PS (M-FPS), (2) medium level of AH with medium PS (M-MPS), (3) high level of AH with fine PS (H-FPS), and (4) high level of AH with medium PS (H MPS). Particle size of AH did not affect total DMI (TDMI) during the preweaning period, although TDMI was greater for calves fed MPS than in those fed FPS during the postweaning and overall periods. Calves fed MPS spent more time eating solid feed and ruminating and less time on nonnutritive oral behaviors compared with FPS calves. The dietary level of AH did not affect behavioral parameters. Average daily gain of calves was not affected by dietary treatment before weaning. During the postweaning and overall periods, average daily gain was greater in calves fed MPS than in those fed FPS at the 25% AH level, but this effect was absent with 12.5% AH. Furthermore, the rumen pH values on d 35 and 70 of the study were greater for MPS than for FPS, regardless of the dietary level of AH. Effects of AH level, PS, and their interaction did not affect blood glucose concentrations in developing calves. These results indicate that feed intake, feeding behavior, rumen fermentation parameters, and blood beta-hydroxybutyrate concentration may be affected by rations differing in forage PS; thus, providing calves with MPS can improve calf performance and reduce their nonnutritive oral behaviors. PMID- 26277319 TI - Feeding preferences and voluntary feed intake of dairy cows: Effect of conservation and harvest time of birdsfoot trefoil and chicory. AB - Bioactive forages contain compounds, such as tannins, that are active against pathogens. They have been successfully used in ruminants to control parasite infections. Because cattle may find bioactive forages unpalatable, it is of interest to know if an afternoon harvest time, which has been shown to increase the percentage of nonstructural carbohydrates (NSC), hence palatability, may mitigate this. The objectives of this study were to quantify voluntary intake and preference of dairy cows for 2 bioactive forages, harvested in the morning and evening, in addition to determining their time spent grazing on each forage species. The forage species evaluated were fresh chicory harvested at 0700 h (FCAM) and 1800 h (FCPM), fresh birdsfoot trefoil harvested at 0700 h (FBAM) and 1800 h (FBPM), birdsfoot trefoil baleage harvested the previous summer at 0700 h (BBAM) and at 1800 h (BBPM), and third-cut alfalfa baleage harvested the previous summer and used as control (CON). Single forages were offered ad libitum in 30 min tests to 14 dairy cows to determine intake in a 7 * 7 Latin square (experiment 1). Every possible pair of forages (21 pairs) was then presented for a 30-min test to 8 different dairy cows, and feed intake was measured (experiment 2). Finally, time spent grazing on chicory and birdsfoot trefoil was measured on 12 dairy cows (experiment 3). The tests consisted of 2 d of restriction on 1 of the 2 fields for 1h, and 2 d of free-choice sessions (1h) between the 2 fields adjacent to each other. Grazing time and location of the animals on the field was assessed through 2-min scan sampling. In experiment 1, the highest voluntary intakes were for CON, BBPM, and BBAM. In experiment 2, BBPM was preferentially consumed over all other forages followed by CON and BBAM. Multidimensional scaling showed that preference for BBPM, CON, and BBAM in dimension 1 was positively associated with dry matter and nitrogen content, and negatively associated with hemicellulose and soluble N/total N. No relationships between dimension coordinates and any of the measured chemical composition variables could be found for the other 2 dimensions. In experiment 3, cows spent 71% of their time grazing in the birdsfoot trefoil field and 23% in the chicory field during the free-choice sessions. In conclusion, cows in the present experiments showed an overall preference toward baled forages compared with fresh forages, most notably toward birdsfoot trefoil baleage. Cow preference did not appear to be linked to harvest time (a.m. vs. p.m.). PMID- 26277320 TI - The origin of the p.E180 growth hormone receptor gene mutation. AB - Laron syndrome, an autosomal recessive condition of extreme short stature, is caused by the absence or dysfunction of the growth hormone receptor. A recurrent mutation in the GHR gene, p.E180, did not alter the encoded amino acid, but activated a cryptic splice acceptor resulting in a receptor protein with an 8 amino acid deletion in the extracellular domain. This mutation has been observed among Sephardic Jews and among individuals in Ecuador, Brazil and Chile, most notably in a large genetic isolate in Loja, Ecuador. A common origin has been postulated based on a shared genetic background of markers flanking this mutation, suggesting that the Lojanos (and others) may have Sephardic (Converso) Jewish ancestry. Analysis of the population structure of Lojanos based on genome wide analysis demonstrated European, Sephardic Jewish and Native American ancestry in this group. X-autosomal comparison and monoallelic Y chromosomal and mitochondrial genetic analysis demonstrated gender-biased admixture between Native American women and European and Sephardic Jewish men. These findings are compatible with the co-occurrence of the Inquisition and the colonization of the Americas, including Converso Jews escaping the Inquisition in the Iberian Peninsula. Although not found among Lojanos, Converso Jews also brought founder mutations to contemporary Hispanic and Latino populations in the BRCA1 (c.68_69delAG) and BLM (c.2207_2212delATCTGAinsTAGATTC) genes. PMID- 26277321 TI - Inhibition of gastric H+,K+-ATPase by 4-(2-butyl-6,7-dichloro-2-cyclopentylindan 1-on-5-yl)oxybutyric acid (DCPIB), an inhibitor of volume-regulated anion channel. AB - 4-(2-Butyl-6,7-dichloro-2-cyclopentylindan-1-on-5-yl)oxybutyric acid (DCPIB) has been used as an inhibitor of volume-regulated anion channel (VRAC), which is expressed in almost all cells (IC50 is around 4 uM). Here, we found that DCPIB significantly inhibited the activities of gastric proton pump (H+,K+-ATPase) in isolated gastric tubulovesicles and the membrane sample of the H+,K+-ATPase expressing cells, and their IC50 values were around 9 uM. In the tubulovesicles, no significant expression of leucine rich repeat containing 8 family member A (LRRC8A), an essential component of VRAC, was observed. The inhibitory effect of DCPIB was also found in the membrane sample obtained from the cells in which LRRC8A had been knocked down. On the other hand, DCPIB had no significant effect on the activity of Na+,K+-ATPase or Ca2+-ATPase. In the H+,K+-ATPase-expressing cells, DCPIB inhibited the 86Rb+ transport activity of H+,K+-ATPase but not that of Na+,K+-ATPase. DCPIB had no effect on the activity of Cl- channels other than VRAC in the cells. These results suggest that DCPIB directly inhibits H+,K+ ATPase activity. DCPIB may be a beneficial tool for studying the H+,K+-ATPase function in vitro. PMID- 26277322 TI - Effect of the potent and selective DP1 receptor antagonist, asapiprant (S 555739), in animal models of allergic rhinitis and allergic asthma. AB - Prostaglandin (PG) D2 elicits responses through either the DP1 and/or DP2 receptor. Experimental evidence suggests that stimulation of the DP1 receptor contributes to allergic responses, such that antagonists are considered to be directed therapies for allergic diseases. In this study, we demonstrate the activity of a novel synthetic DP1 receptor antagonist termed asapiprant (S 555739) for the DP1 receptor and other receptors in vitro, and assess the efficacy of asapiprant in several animal models of allergic diseases. We determined the affinity and selectivity of asapiprant for the DP1 receptor in binding assays. In the animal models of allergic rhinitis, changes in nasal resistance, nasal secretion, and cell infiltration in nasal mucosa were assessed after antigen challenge with and without asapiprant. Similarly, in the animal models of asthma, the effect of antigen challenge with and without asapiprant on antigen-induced bronchoconstriction, airway hyper-responsiveness, mucin production, and cell infiltration in lung were assessed. In binding studies, asapiprant exhibited high affinity and selectivity for the DP1 receptor. Significant suppression of antigen-induced nasal resistance, nasal secretion, and cell infiltration in nasal mucosa was observed with asapiprant treatment. In addition, treatment with asapiprant suppressed antigen-induced asthmatic responses, airway hyper-responsiveness, and cell infiltration and mucin production in lung. These results show that asapiprant is a potent and selective DP1 receptor antagonist, and exerts suppressive effects in the animal models of allergic diseases. Thus, asapiprant has potential as a novel therapy for allergic airway diseases. PMID- 26277323 TI - Facilitatory effect of dopamine on neuromuscular transmission mediated via dopamine D1-like receptors and prospective interaction with nicotine. AB - The objective of this study is to probe the effects of dopamine and potential interactions with nicotine at the motor end plate. To accomplish this, we measured the amplitude of nerve-evoked muscle twitches of the isolated rat phrenic hemi-diaphragm preparation. Dopamine potentiated indirect muscle twitches in normal and gallamine-presensitized preparations amounting to a maximum of 31.14+/-0.71% and 69.23+/-1.96%, respectively. The dopamine-induced facilitation was well maintained in presence of 10 uM propranolol but greatly reduced in presence of 6 uM SCH 23390 or 3 uM dantrolene. In addition, SKF 81297 attained a plateau at 16 uM as opposed to 64 uM dopamine, with a percentage potentiation of 69.47+/-1.76. The facilitatory effect of dopamine was potentiated in nicotine treated rats. This study revealed for the first time that the facilitatory effect exerted by dopamine on neuromuscular transmission is mediated via the dopamine D1 like receptors. In addition, it highlighted the possible dependency of dopamine effects on intracellular calcium and signified potential interaction among dopamine and nicotine. Clinically, the findings generated by this study reveal potential targets for approaching motor deficit syndromes. PMID- 26277324 TI - Nociceptin/orphanin FQ receptor and pain: Feasibility of the fourth opioid family member. AB - The pharmacological management of chronic pain is a major therapeutic problem. The need of repeated treatments reduces the usefulness of classical analgesic drugs, like MU opioid receptor (MOP) agonists, characterized by tolerance development, side effects and abuse. Moreover, the pathological persistence of pain modifies nociceptive signals and pain-devoted structure activity weakening MOP agonists and making difficult the research of new active molecules. Nociceptine/orphanin FQ (N/OFQ) and its receptor (NOP) offers a peculiar opioid system able to interact with MOP receptors and made more sensitive by chronic pain conditions. The pain reliever efficacy of NOP agonists against persistent pain, mainly neuropathic pain, has been highlighted after intrathecal infusions in rats and non human primates (NHPs). The differences emerged between the effects of NOP stimulation in rodents and NHPs allow to hypothesize the relevance of NOP modulators in higher organisms strongly encouraging the development of compounds active by a systemic route. Possible applicative perspectives are (i) selective NOP agonists as such, (ii) NOP modulation as adjuvant of MOP-based treatments, or (iii) mixed non-selective agonists vs NOP and classical opioid receptors. PMID- 26277325 TI - Reduction in renal blood flow following administration of norepinephrine and phenylephrine in septic rats treated with Kir6.1 ATP-sensitive and KCa1.1 calcium activated K+ channel blockers. AB - We evaluated the effects of K+ channel blockers in the vascular reactivity of in vitro perfused kidneys, as well as on the influence of vasoactive agents in the renal blood flow of rats subjected to the cecal ligation and puncture (CLP) model of sepsis. Both norepinephrine and phenylephrine had the ability to increase the vascular perfusion pressure reduced in kidneys of rats subjected to CLP at 18 h and 36 h before the experiments. The non-selective K+ channel blocker tetraethylammonium, but not the Kir6.1 blocker glibenclamide, normalized the effects of phenylephrine in kidneys from the CLP 18 h group. Systemic administration of tetraethylammonium, glibenclamide, or the KCa1.1 blocker iberiotoxin, did not change the renal blood flow in control or septic rats. Norepinephrine or phenylephrine also had no influence on the renal blood flow of septic animals, but its injection in rats from the CLP 18 h group previously treated with either glibenclamide or iberiotoxin resulted in an exacerbated reduction in the renal blood flow. These results suggest an abnormal functionality of K+ channels in the renal vascular bed in sepsis, and that the blockage of different subtypes of K+ channels may be deleterious for blood perfusion in kidneys, mainly when associated with vasoactive drugs. PMID- 26277326 TI - The dynamic blood-brain barrier. AB - With the endothelium as its central unit, the blood-brain barrier (BBB) is a complex multicellular structure separating the central nervous system (CNS) from the systemic circulation. Disruption of the BBB has now been implicated in a multitude of acute and chronic CNS disorders indicating the potentially devastating effects of BBB breakdown on brain function. However, the healthy BBB is not an impermeable wall, but rather a communication 'centre', responding to and passing signals between the CNS and blood. New studies are identifying BBB specific transport pathways that tightly regulate the entry and exit of molecules to and from the brain. They are revealing a highly plastic barrier in which dynamic changes in BBB components like paracellular tight junction complexes can contribute to BBB maintenance. Here, we provide a succinct overview of the current state-of-play in BBB research and summarize novel findings into BBB regulation in homeostatic regulation of the brain. PMID- 26277327 TI - Self-Guided Supramolecular Cargo-Loaded Nanomotors with Chemotactic Behavior towards Cells. AB - Delivery vehicles that are able to actively seek and precisely locate targeted tissues using concentration gradients of signaling molecules have hardly been explored. The directed movement toward specific cell types of cargo-loaded polymeric nanomotors along a hydrogen peroxide concentration gradient (chemotaxis) is reported. Through self-assembly, bowl-shaped poly(ethylene glycol)-b-polystyrene nanomotors, or stomatocytes, were formed with platinum nanoparticles entrapped in the cavity while a model drug was encapsulated in the inner compartment. Directional movement of the stomatocytes in the presence of a fuel gradient (chemotaxis) was first demonstrated in both static and dynamic systems using glass channels and a microfluidic flow. The highly efficient response of these motors was subsequently shown by their directional and autonomous movement towards hydrogen peroxide secreting neutrophil cells. PMID- 26277328 TI - Metastatic spread pattern after curative colorectal cancer surgery. A retrospective, longitudinal analysis. AB - OBJECTIVE: The most common sites of colorectal cancer (CRC) recurrence are the local tissues, liver or lungs. The objective was to identify risk factors associated with the primary CRC tumor and cancer recurrence in these anatomical sites. METHODS: Retrospective, longitudinal analyses of data on CRC survivors. Multivariable Cox regression analysis was performed to examine the association between possible cofounders with recurrence to various anatomical sites. RESULTS: Data for 10,398CRC survivors (tumor location right colon=3870, left colon=2898, high rectum=2569, low rectum=1061) were analyzed; follow up time was up to five years. Mean age at curative surgery was 71.5 (SD 11.8) years, 20.2% received radio-chemotherapy, stage T3 (64.4%) and N0 (65.1%) were most common. Overall 1632 (15.7%) had cancer recurrence (Isolated liver n=412, 3,8%; isolated lung n=252, 2,4%; isolated local n=223, 2.1%). Risk factors associated with recurrent CRC were identified, i.e. isolated liver metastases (male: Adjusted Hazard Ratio (AHR) 1,45; colon left: AHR 1,63; N2 disease: AHR 3,35; T2 disease: AHR 2,82), isolated lung metastases (colon left: AHR 1,53; rectum high: AHR 2,48; rectum low: AHR 2,65; N2 disease 3,76), and local recurrence (glands examined<12: AHR 1,51; CRM <3mm: AHR 1,60; rectum high: AHR 2,15; N2 disease: AHR 2,58) (all p values <0001). CONCLUSION: Our study finds that the site of the primary CRC tumor is associated with location of subsequent metastasis. Left sided colon cancers have increased risk of metastatic spread to the liver, whereas rectal cancers have increased risk of local recurrence and metastatic spread to the lungs. These results, in combination with other risk factors for CRC recurrence, should be taken into consideration when designing risk adapted post-treatment CRC surveillance programs. PMID- 26277329 TI - Increasing trends in cervical cancer mortality among young Japanese women below the age of 50 years: an analysis using the Kanagawa population-based Cancer Registry, 1975-2012. AB - BACKGROUND: In Japan, cervical cancer (CC) deaths among women aged <50 years have doubled over the last three decades. Obtaining age-specific CC mortality rates among young women is important for taking measures against CC. Age-adjusted CC mortality rates for all ages are inadequate because of the classification of 'uterine cancer, not otherwise specified' (NOS uterine cancer) and CC mortality rates among elderly women. The aim of the present study was to calculate exact age-specific CC mortality rates in women aged <50 years in Kanagawa, taking into account the impact of NOS uterine cancer. METHODS: Using the Kanagawa Cancer Registry, CC deaths (1975-2012) were analyzed and CC mortality rates (age adjusted, 20-29, 30-49, and >=50 years) were calculated. In addition, hospitals were surveyed to reclassify cases of NOS uterine cancer. After reclassification, chronological trends were also analyzed. RESULTS: Age-specific CC mortality rates in Kanagawa and Japan overall showed increasing trends for ages 20-29 (P for trend<0.001) and 30-49 (P for trend<0.001). Rates of NOS uterine cancer death were significantly lower in Kanagawa than in Japan overall (P<0.05), except for patients aged <50 years in 2005-2009 (P=0.159). CONCLUSIONS: The present study revealed concern for CC among Japanese women younger than 50 years. Well organized CC screening and HPV vaccination should be provided to reduce CC mortality rates for these young women. PMID- 26277330 TI - Trends in survival of multiple myeloma: a thirty-year population-based study in a single institution. AB - BACKGROUND: Despite the progress made in recent years, multiple myeloma is still considered an incurable disease. Most survival data come from clinical trials. Little is known about the outcome in unselected real-life patients. METHODS: Overall survival was analyzed in a cohort of newly diagnosed symptomatic multiple myeloma patients, over the last three decades, in a single institution population based study. RESULTS: 582 consecutive myeloma patients were included in the study. Survival increased over time in patients younger than 65 years but did not reach statistical significance in patients with 65 years or older. The prognostic factors associated with overall survival were the International Staging System, the serum lactate dehydrogenase level, the renal impairment, the realization of autologous stem cell transplantation, and the presence of concomitant amyloidosis. Overall survival shows a steady improvement over time. INTERPRETATION: The survival of myeloma is improving progressively in real-life patients, particularly after the widespread use of the novel agents. A comprehensive assessment of comorbidity can help to explain the huge heterogeneity of myeloma outcome. The optimization of current therapeutic resources as well as the incorporation of new drugs will allow further improvement of survival in the coming years. PMID- 26277331 TI - Case series: A novel technique for the treatment of external auditory canal stenosis. AB - External auditory canal (EAC) stenosis can exist as an isolated problem, as a component of craniofacial disorders, or in association with genetic syndromes. We present five cases and demonstrate the efficacy of a minimally invasive way of opening the EAC, facilitating better hearing, easier office examination, and allowing for other necessary treatments such as ear tube placement or use of a hearing aid. Follow-up ranged from 1 to 19 months, with all patients demonstrating significant improvement. We believe this is a novel surgical approach which is easy to perform, cost effective, and may be applicable to a wide range of patients. PMID- 26277332 TI - An overview of the clinical application of antisense oligonucleotides for RNA targeting therapies. AB - Despite the discovery more than two decades ago that antisense oligonucleotides (ASOs) could be used to modulate protein expression, there have been only two antisense drugs approved for clinical use till date. Despite this low success rate, the antisense field is undergoing resurgence due to the development of more potent and nuclease resistant chemistries, as well as nanoparticle delivery systems that enhance delivery to target tissues. In this review, we introduce the predominant therapeutic strategies in the antisense field whilst highlighting recent clinical findings that demonstrate the significant potential of these approaches for development of novel therapies in several diseases. PMID- 26277333 TI - 2015 Residency Match Update and the Radiology Stock Market. PMID- 26277334 TI - Avoid "Cannot Exclude": Make a Diagnosis. PMID- 26277335 TI - Maternal collapse: Training in resuscitation. AB - The National Committee for the Confidential Enquiries into Maternal Deaths (NCCEMD) of South Africa has recommended in the Sixth Saving Mothers Report that health-care professionals (HCPs) training in managing obstetric emergencies be improved. One such measure is to ensure that the Essential Steps in Managing Obstetric Emergencies (ESMOE) with its Emergency Obstetric Simulation Training (EOST) be rolled out to every HCP working in the obstetric environment. The programme has been strengthened and rolled out in the province of KwaZulu-Natal, South Africa. This review focuses on the various teaching methods used to improve maternal resuscitation training in a South African context. Evidence-based interventions in maternal resuscitation will be highlighted, and recommendations for clinical practice will be suggested. Common causes of maternal collapse will be explored, and measures to improve training in these areas will be outlined. In order to ensure sustainability, quality improvement measures need to be introduced and evaluated. PMID- 26277336 TI - Surgeon motivations behind the timing of breast reconstruction in patients requiring postmastectomy radiation therapy. AB - OBJECTIVES: Although postmastectomy radiation therapy (PMRT) has been shown to reduce breast cancer burden and improve survival, PMRT may negatively influence outcomes after reconstruction. The goal of this study was to compare current opinions of plastic and reconstructive surgeons (PRS) and surgical oncologists (SO) regarding the optimal timing of breast reconstruction for patients requiring PMRT. METHODS: Members of the American Society of Plastic Surgeons (ASPS), the American Society of Breast Surgeons (ASBS), and the Society of Surgical Oncology (SSO) were asked to participate in an anonymous web-based survey. Responses were solicited in accordance to the Dillman method, and they were analyzed using standard descriptive statistics. RESULTS: A total of 330 members of the ASPS and 348 members of the ASBS and SSO participated in our survey. PRS and SO differed in patient-payor mix (p < 0.01) and practice setting (p < 0.01), but they did not differ by urban versus rural setting (p = 0.65) or geographic location (p = 0.30). Although PRS favored immediate reconstruction versus SO, overall timing did not significantly differ between the two specialists (p = 0.14). The primary rationale behind delayed breast reconstruction differed significantly between PRS and SO (p < 0.01), with more PRS believing that the reconstructive outcome is significantly and adversely affected by radiation. Both PRS and SO cited "patient driven desire to have immediate reconstruction" (p = 0.86) as the primary motivation for immediate reconstruction. CONCLUSIONS: Although the optimal timing of reconstruction is controversial between PRS and SO, our study suggests that the timing of reconstruction in PMRT patients is ultimately driven by patient preferences and the desire of PRS to optimize aesthetic outcomes. PMID- 26277337 TI - Microvascular vessel preparation: What are we really removing during adventitial stripping? AB - AIM: Although adventitial stripping has been routinely recommended and practiced during vessel preparation for microsurgical anastomoses, detailed descriptions vary regarding the adequate extent of such maneuver. We aimed to histologically clarify which components of the vessel are removed during adventitial stripping, using arterial samples harvested during microsurgical breast reconstruction. METHODS: Thirteen deep inferior epigastric arteries, nine internal mammary arteries, and four thoracodorsal arteries were evaluated in each step of vessel preparation, which were (1) grossly as a vascular bundle, (2) before vessel preparation, and (3) after vessel preparation under the operative microscope. Histologic components of each sample were evaluated under light microscopy. The combined thickness of the intima and the media and the thickness of the adventitia were measured and compared. RESULTS: Two distinctive layers of connective tissue were observed outside the media before vessel preparation. Outer loose areolar tissue with coarse fibers was mostly removed during vessel preparation. However, the inner adventitial layer with dense, fine collagen fibers consistently remained after vessel preparation and ostensible adventitial stripping. The average thickness of this layer was comparable with that of the media. Although there was no definitive demarcation between the two differential connective tissue layers, a vasa vasorum layer was distinctly seen between the two layers. CONCLUSION: The tissue removed during standard microsurgical vessel preparation or vessel stripping is not the entire layer of the adventitia, and the inner adherent layer of adventitia with fine collagen fibers should be preserved and included in the microsuture with the intima and media during anastomosis. PMID- 26277338 TI - Reply: To PMID 26135812. PMID- 26277339 TI - Editorial Comment. PMID- 26277340 TI - The auxiliary subunits Neto1 and Neto2 have distinct, subunit-dependent effects at recombinant GluK1- and GluK2-containing kainate receptors. AB - The kainate-type of ionotropic glutamate receptors are assembled from a combination of five different pore-forming subunits (GluK1-5), which confer distinct functional and pharmacological properties. These receptors are also modulated by co-assembly with the auxiliary subunits Neto1 and Neto2. To determine the impact of variation in subunit composition on the functional interaction between kainate receptors and Neto subunits, the Neto subunits were combined with either GluK1 or GluK2 in HEK-293T cells and responses to glutamate examined through patch-clamp recordings. Co-expression of GluK1 with either Neto1 or Neto2 caused a substantial increase in glutamate sensitivity and a slowing of the onset of desensitization at low agonist concentrations. However, at higher glutamate concentrations the primary effect of Neto2 was to slow the onset of desensitization, while that of Neto1 was to increase recovery from desensitization. In contrast, co-expression of Neto2 with GluK2 homomeric receptors had only modest effects on glutamate sensitivity, but increased the rate of recovery from desensitization as well as slowing its onset at all agonist concentrations. The properties of chimeric Neto1/Neto2 subunits suggested that the extracellular N-terminal region including the two CUB domains was largely responsible for the distinct regulatory effects of Neto1 and Neto2 on the desensitization properties of GluK1 homomeric receptors. These results further demonstrate that the functional effects of Neto subunits depend upon the subunit identity of both the auxiliary and the pore-forming subunits. PMID- 26277341 TI - Upregulation of orexin receptor in paraventricular nucleus promotes sympathetic outflow in obese Zucker rats. AB - Sympathetic vasomotor tone is elevated in obesity-related hypertension. Orexin importantly regulates energy metabolism and autonomic function. We hypothesized that alteration of orexin receptor in the paraventricular nucleus (PVN) of the hypothalamus leads to elevated sympathetic vasomotor tone in obesity. We used in vivo measurement of sympathetic vasomotor tone and microinjection into brain nucleus, whole-cell patch clamp recording in brain slices, and immunocytochemical staining in obese Zucker rats (OZRs) and lean Zucker rats (LZRs). Microinjection of orexin 1 receptor (OX1R) antagonist SB334867 into the PVN reduced basal arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) in anesthetized OZRs but not in LZRs. Microinjection of orexin A into the PVN produced greater increases in ABP and RSNA in OZRs than in LZRs. Western blot analysis revealed that OX1R expression levels in the PVN were significantly increased in OZRs compared with LZRs. OX1R immunoreactivity was positive in retrogradely labeled PVN-spinal neurons. The basal firing rate of labeled PVN spinal neurons was higher in OZRs than in LZRs. SB334867 decreased the basal firing activity of PVN-spinal neurons in OZRs but had no effect in LZRs. Orexin A induced a greater increase in the firing rate of PVN-spinal neurons in OZRs than in LZRs. In addition, orexin A induced larger currents in PVN-spinal neurons in OZRs than in LZRs. These data suggest that upregulation of OX1R in the PVN promotes hyperactivity of PVN presympathetic neurons and elevated sympathetic outflow in obesity. PMID- 26277343 TI - Delayed facial palsy in Miller Fisher syndrome. AB - Miller Fisher syndrome is characterised by the triad of ophthalmoplegia, ataxia and areflexia. However, facial palsy can occur during the course of the illness although development of facial palsy when other cardinal signs of Miller Fisher syndrome have reached nadir or improving, is unusual. This delayed appearance of facial palsy can be easily overlooked by the treating clinician. Here, we report four patients with Miller Fisher syndrome and delayed-onset facial palsy. We discuss the possible underlying reasons behind the delay in facial palsy. PMID- 26277342 TI - Dopaminergic and cholinergic regulation of Fyn tyrosine kinase phosphorylation in the rat striatum in vivo. AB - Src and Fyn are two Src family kinase (SFK) members that are expressed in mammalian brains and play important roles in the regulation of a variety of neuronal and synaptic substrates. Here we investigated the responsiveness of these SFKs to changing dopamine receptor signals in dopamine responsive regions of adult rat brains in vivo. Pharmacological activation of dopamine D1 receptors (D1Rs) by a systemic injection of the selective agonist SKF81297 increased phosphorylation of SFKs at a conserved and activation-associated autophosphorylation site (Y416) in the striatum, indicating activation of SFKs following SKF81297 injection. The dopamine D2 receptor (D2R) agonist quinpirole had no effect. Blockade of D1Rs with an antagonist SCH23390 did not alter striatal Y416 phosphorylation, while the D2R antagonist eticlopride elevated it. Between Src and Fyn, SKF81297 seemed to preferentially facilitate Fyn phosphorylation. Activation of muscarinic acetylcholine M4 receptors (M4Rs) with a positive allosteric modulator VU0152100 suppressed SFK Y416 responses to SKF81297. Additionally, SKF81297 induced a correlated increase in phosphorylation of N-methyl-D-aspartate (NMDA) receptor GluN2B subunits at a Fyn site (Y1472), which was attenuated by VU0152100. SKF81297 also enhanced synaptic recruitments of active Fyn and GluN1/GluN2B-containing NMDA receptors. These data demonstrate that D1Rs regulate Fyn and downstream NMDA receptors in striatal neurons in vivo. Acetylcholine through activating M4Rs inhibits Fyn and NMDA receptors in their sensitivity to D1R signaling. PMID- 26277344 TI - Coronary events in obese hemodialysis patients before and after renal transplantation. AB - We examined the impact of obesity (BMI >=30 kg/m(2) , n = 357) on prognosis in 1696 hemodialysis (HD) patients before and after renal transplantation (TX). End points were coronary events, composite cardiovascular (CV) events, and death. Obese HD patients were older (55.9 +/- 9.2 vs. 54.2 +/- 11), had more diabetes (54% vs. 40%), dyslipidemia (49% vs. 30%), altered myocardial scan (38% vs. 31%), myocardial infarction (MI) (16% vs. 10%), coronary intervention (11% vs. 7%), higher total cholesterol (186 +/- 52 vs. 169 +/- 47), and triglycerides (219 +/- 167 vs. 144 +/- 91). Obese undergoing TX had more dyslipidemia (46% vs. 31%), angina (23% vs. 14%), MI (18% vs. 5%), increased total cholesterol (185 +/- 56 vs. 172 +/- 48), and triglycerides (237 +/- 190 vs. 149 +/- 100). Obesity was independently associated with coronary events (log-rank = 0.008, HR 2.55% CI 1.27 5.11) and death (log-rank 0.046, HR 1.52, % CI 1.007-2.30) in TX but not in HD. Obese HD patients had more risk factors and ischemic heart disease, but these characteristics did not interfere with prognosis. In TX patients, obesity predicts coronary events and death. PMID- 26277345 TI - The carriage of the serine-aspartate repeat protein-encoding sdr genes among Staphylococcus aureus lineages. AB - The serine-aspartate repeat proteins (Sdr) are members of a family of surface proteins and contribute to the pathogenicity of Staphylococcus aureus. Among 288 S. aureus isolates including 158 and 130 associated with skin and soft tissue infections and bloodstream infection, respectively; 275 (95.5%) were positive for at least one of three sdr genes tested. The positivity rates for sdrC, sdrD, and sdrE among S. aureus isolates were 87.8% (253/288), 63.9% (184/288), and 68.1% (196/288), respectively. 224 (77.8%) of 288 isolates were concomitantly positive for two or three sdr genes. There was an association between carriage of sdrE and methicillin-resistant S. aureus (MRSA) isolates, while the carriage rates of sdrC and sdrD in MRSA isolates were similar to those in methicillin-sensitive S. aureus (MSSA) isolates. The prevalence of co-existence of sdrC and sdrE among MRSA isolates was significantly higher than that among MSSA isolates (p<0.05). All ST1, ST5, ST7, and ST25 isolates were positive for sdrD. While all ST121 and ST398 isolates were negative for sdrD. All ST59 and ST88 isolates were positive for sdrE. All ST1 isolates were concomitantly positive for sdrC and sdrD. Concomitant carriage of sdrC, sdrD, and sdrE was found among all ST5, 75.0% (9/12) of ST1, 69.2% (9/13) of ST6, 78.6% (11/14) of ST25, and 90.9% (20/22) of ST88 isolates. sdrD was linked to CC5, CC7 and CC88 isolates, especially CC88 isolates. There was a strong association between the presence of sdrE and CC59, CC88, and CC5 isolates. A significant correlation between concomitant carriage of sdrC, sdrD, and sdrE and CC88 isolates was found. sdrC-positive, sdrD-positive and sdrE-negative gene profile was significantly associated with CC7 clone. There was an association between sdrC-positive, sdrD-negative, and sdrE-positive gene profile and CC59 isolates. A correlation between sdrC-positive, sdrD-negative, and sdrE-negative gene profile and CC121 clone was found. More CC59 isolates carried sdrC-negative, sdrD-negative, and sdrE-positive gene profile relative to other four CCs isolates. All ST1 and ST5, 95.2% (20/21) of ST188 and 95.2% (20/21) of ST630 isolates were positive for sdrC. Taken together, our investigation indicated that different S. aureus lineages were associated with specific patterns of carriage of sdr genes. PMID- 26277346 TI - Thermal Effects and Structural Changes of Photosynthetic Reaction Centers Characterized by Wide Frequency Band Hydrophone: Effects of Carotenoids and Terbutryn. AB - Photothermal characteristics and light-induced structural (volume) changes of carotenoid-containing and noncontaining photosynthetic reaction centers (RCs) were investigated by wide frequency band hydrophone. We found that the presence of carotenoid either does not play considerable role in the light-induced conformational movements, or these rearrangements are too slow for inducing a photoacoustic (PA) signal. The kinetic component with a few tens of microseconds, exhibited by the carotenoid-less RCs, appears to be similar to that of triplet state lifetimes, identified by other methods. The binding of terbutryn to the acceptor side is shown to affect the dynamics of the RC. Our results do not confirm large displacements or volume changes induced by the charge movements and by the charge relaxation processes in the RCs in few hundreds of microseconds time scale that accompanies the electron transfer between the primary and secondary electron acceptor quinones. PMID- 26277347 TI - Biodegradation of benzalkonium chlorides singly and in mixtures by a Pseudomonas sp. isolated from returned activated sludge. AB - Bactericidal cationic surfactants such as quaternary ammonium compounds (QACs) are widely detected in the environment, and found at mg kg(-1) concentrations in biosolids. Although individual QACs are amenable to biodegradation, it is possible that persistence is increased for mixtures of QACs with varying structure. The present study evaluated the biodegradation of benzyl dimethyl dodecyl ammonium chloride (BDDA) singly and in the presence of benzyl dimethyl tetradecyl ammonium chloride (BDTA) using Pseudomonas sp., isolated from returned activated sludge. Growth was evaluated, as was biodegradation using (14)C and HPLC-MS methods. BDTA was more toxic to growth of Pseudomonas sp. compared to BDDA, and BDTA inhibited BDDA biodegradation. The benzyl ring of [U-(14)C-benzyl] BDDA was readily and completely mineralized. The detection of the transformation products benzyl methyl amine and dodecyl dimethyl amine in spent culture liquid was consistent with literature. Overall, this study demonstrates the antagonistic effect of interactions on biodegradation of two widely used QACs suggesting further investigation on the degradation of mixture of QACs in wastewater effluents and biosolids. PMID- 26277348 TI - Signs of stress on soft surfaces : A commentary on: Cui, Y., F.M. Hameed, B. Yang, K. Lee, C.Q. Pan, S. Park, and M. Sheetz. 2015. Cyclic stretching of soft substrates induces spreading and growth. Nat Commun. 6:6333. AB - Cells experience mechanical stimuli during growth and differentiation and transduce these stimuli into biochemical signals that in turn regulate cell responses to the imposed forces. Reduced spreading and impaired stress fiber formation are indicators of the mechano-response to growth on soft elastic culture substrates. However, Cui and coworkers demonstrate that cell spreading and stress fiber formation on soft substrates is possible if simultaneous cyclic stretching compensates for the lack of substrate stiffness-induced cell stress. The stress(ed) response is dependent on cyclic stretch amplitude and frequency and, at least in part, mediated by myocardin related transcription factor A (MRTF A) and Yes-associated protein (YAP). The study thus provides novel insight into the mechanisms of cell mechanosensing and how materials can be designed to mimic mechanical conditions of body tissues. PMID- 26277349 TI - Medication-Related Osteonecrosis of the Jaw: Basic and Translational Science Updates. AB - In the late 1990s and the early 2000s, bisphosphonates had become the clinical pillar of excellence for treating metabolic bone disease, and thus their connection with osteonecrosis of the jaw (ONJ) caused significant concern. Over the past decade, progress has been made in understanding what is now referred to as medication-related ONJ (MRONJ), because of its connections to agents other than bisphosphonates, although in many respects the progress has been slow. This review highlights the key basic science and translational (animal) studies in the area of MRONJ and suggests areas of focus as the field moves into the next decade. PMID- 26277350 TI - EMF radiations (1800 MHz)-inhibited early seedling growth of maize (Zea mays) involves alterations in starch and sucrose metabolism. AB - The present study investigated the impact of 1800-MHz electromagnetic field radiations (EMF-r), widely used in mobile communication, on the growth and activity of starch-, sucrose-, and phosphate-hydrolyzing enzymes in Zea mays seedlings. We exposed Z. mays to modulated continuous wave homogenous EMF-r at specific absorption rate (SAR) of 1.69+/-0.0 * 10(-1) W kg(-1) for 1/2, 1, 2, and 4 h. The analysis of seedlings after 7 days revealed that short-term exposure did not induce any significant change, while longer exposure of 4 h caused significant growth and biochemical alterations. There was a reduction in the root and coleoptile length with more pronounced effect on coleoptile growth (23 % reduction on 4-h exposure). The contents of photosynthetic pigments and total carbohydrates declined by 13 and 18 %, respectively, in 4-h exposure treatments compared to unexposed control. The activity of starch-hydrolyzing enzymes-alpha- and beta-amylases-increased by ~92 and 94 %, respectively, at an exposure duration of 4 h, over that in the control. In response to 4-h exposure treatment, the activity of sucrolytic enzymes-acid invertases and alkaline invertases-was increased by 88 and 266 %, whereas the specific activities of phosphohydrolytic enzymes (acid phosphatases and alkaline phosphatases) showed initial increase up to <=2 h duration and then declined at >2 h exposure duration. The study concludes that EMF-r-inhibited seedling growth of Z. mays involves interference with starch and sucrose metabolism. PMID- 26277351 TI - Apoptosis and necrosis during the circadian cycle in the centipede midgut. AB - Three types of cells have been distinguished in the midgut epithelium of two centipedes, Lithobius forficatus and Scolopendra cingulata: digestive, secretory, and regenerative cells. According to the results of our previous studies, we decided to analyze the relationship between apoptosis and necrosis in their midgut epithelium and circadian rhythms. Ultrastructural analysis showed that these processes proceed in a continuous manner that is independent of the circadian rhythm in L. forficatus, while in S. cingulata necrosis is activated at midnight. Additionally, the description of apoptosis and necrosis showed no differences between males and females of both species analyzed. At the beginning of apoptosis, the cell cytoplasm becomes electron-dense, apparently in response to shrinkage of the cell. Organelles such as the mitochondria, cisterns of endoplasmic reticulum transform and degenerate. Nuclei gradually assume lobular shapes before the apoptotic cell is discharged into the midgut lumen. During necrosis, however, the cytoplasm of the cell becomes electron-lucent, and the number of organelles decreases. While the digestive cells of about 10 % of L. forficatus contain rickettsia-like pathogens, the corresponding cells in S. cingulata are free of rickettsia. As a result, we can state that apoptosis in L. forficatus is presumably responsible for protecting the organism against infections, while in S. cingulata apoptosis is not associated with the elimination of pathogens. Necrosis is attributed to mechanical damage, and the activation of this process coincides with proliferation of the midgut regenerative cells at midnight in S. cingulata. PMID- 26277353 TI - Pollen and microsporangium development in Hovenia dulcis (Rhamnaceae): a different type of tapetal cell ultrastructure. AB - Despite that there is some literature on pollen morphology of Rhamnaceae, studies addressing general aspects of the microsporogenesis, microgametogenesis, and anther development are rare. The aim of this paper is to describe the ultrastructure of pollen grain ontogeny with special attention to tapetum cytology in Hovenia dulcis. Anthers at different stages of development were processed for transmission and scanning electron microscopy, bright-field microscopy, and fluorescence microscopy. Different histochemical reactions were carried out. The ultrastructural changes observed during the development of the tapetal cells and pollen grains are described. Large vesicles containing carbohydrates occur in the tapetal cell cytoplasm during the early stages of pollen development. Its origin and composition are described and discussed. This is the first report on the ontogeny and ultrastructure of the pollen grain and related sporophytic structures of H. dulcis. PMID- 26277352 TI - Cytological characterization of anther development in Panax ginseng Meyer. AB - Ginseng (Panax ginseng), a valued medicinal herb, is a slow-growing plant that flowers after 3 years of growth with the formation of a solitary terminal umbel inflorescence. However, little is known about cytological events during ginseng reproduction, such as the development of the male organ, the stamen. To better understand the mechanism controlling ginseng male reproductive development, here, we investigated the inflorescence and flower structure of ginseng. Moreover, we performed cytological analysis of anther morphogenesis and showed the common and specialized cytological events including the formation of four concentric cell layers surrounding male reproductive cells followed by subsequent cell differentiation and degeneration of tapetal cells, as well as the formation of mature pollen grains via meiosis and mitosis during ginseng anther development. Particularly, our transverse section and microscopic observations showed that the ginseng tapetal layer exhibits obvious nonsynchronous cell division evidenced by the observation of one or two tapetal layers frequently observed in one anther lobe, suggesting the unique control of cell division. To facilitate the future study on ginseng male reproduction, we grouped the anther development into 10 developmental stages according to the characterized cytological events. PMID- 26277354 TI - Depressive symptomatology in patients with metabolic syndrome: A cross-sectional study of stable coronary artery disease patients. PMID- 26277355 TI - Randomized Prospective Clinical Trial Comparing Room Temperature and Warmed Intravenous Fluid Boluses on Pediatric Patients' Comfort. AB - A common complaint among pediatric patients receiving an intravenous (IV) fluid bolus is that their arm feels cold and uncomfortable. The purpose of this study is to test if administering warmed IV fluids, as compared to room temperature IV fluids, results in increased comfort among pediatric patients seeking care in an emergency department. A blinded randomized controlled trial was conducted and 126 pediatric patients were enrolled. Each patient's overall comfort, arm comfort, and arm temperature were measured prior to IV fluid administration, 15 minutes after the beginning of the infusion, and at the end of the 60-minute infusion. After the first 15 minutes of IV fluid administration, the patients who received warmed IV fluids reported higher comfort than the patients who received room temperature IV fluids, t(118)=2.04, p=0.04. Additionally, patients who received the room temperature IV fluids reported that their arms felt cooler than patients who received the warmed fluids, t(118)=3.25, p=0.0015. Warming IV fluids has the potential to improve the experience of IV bolus administration for pediatric patients. PMID- 26277356 TI - Ghrelin Inhibits Interleukin-6 Production Induced by Cigarette Smoke Extract in the Bronchial Epithelial Cell Via NF-kappaB Pathway. AB - Cigarette smoke (CS)-induced airway inflammation is the main pathogenesis of COPD. The present study was designed to evaluate whether ghrelin, a novel growth hormone-releasing peptide, can affect the pro-inflammatory cytokine interleukin-6 (IL-6) production induced by cigarette smoke extract (CSE) in the human bronchial epithelial cell line (16-HBE) and its possible mechanism. 16-HBE cells were pre incubated with vehicle or ghrelin (0.1 to 1000 ng/mL) in a concentration dependent manner, and then CSE (0 to 16 %) was added. The protein levels of IL-6 in the medium were determined by ELISA, and the mRNA expressions of IL-6 was detected by RT-PCR. We also detected the phosphorylation of IKKalpha/beta/p65 protein and the degradation of inhibitory protein-kappaB (I-kappaB) by Western blot analysis. And the generation of reactive oxygen species (ROS) in 16-HBE was evaluated by labeling specific fluorescence probes DCFH-DA. 16-HBE Cells treated with CSE (8 %) exhibited significantly higher IL-6 production compared with cells treated with vehicle alone (P < 0.05). Ghrelin suppressed CSE-induced IL-6 production at both mRNA and protein levels in a concentration-dependent manner (P < 0.05). Moreover, ghrelin attenuated CSE-triggered NF-kappaB activation in 16 HBE, but the intracellular ROS level after application of CSE was not affected by ghrelin (0.1 to 1000 ng/mL). Together, these results suggest that ghrelin inhibits CSE-induced IL-6 production in 16-HBE cells by targeting on NF-kappaB pathway, but not by scavenging intracellular ROS. PMID- 26277357 TI - Silencing Triggering Receptors Expressed on Myeloid Cells-1 Impaired the Inflammatory Response to Oxidized Low-Density Lipoprotein in Macrophages. AB - Atherosclerosis is a chronic progressive inflammatory disease characterized by the accumulation of lipid contents in arterial walls. Previous studies suggest participation of Toll-like receptors (TLRs) in lipid deposition and inflammatory response in vascular wall. The triggering receptor expressed on myeloid cells 1 (TREM-1) is a cell surface receptor of the immunoglobulin superfamily, which amplifies signal transduction of TLR pathway and enhances immune response to microbial infections. The aim of the present study was to investigate the effect of the oxidized low-density lipoprotein (oxLDL) on the expression of the TREM-1, as well as its engagement in proinflammatory cytokine production and foam cell formation in RAW264.7 mice macrophages. oxLDL enhanced TREM-1 and TLR-4, but not TLR-2 gene expression in macrophages; furthermore, silencing TREM-1 expression by short hairpin interfering RNA inhibited lipid phagocytosis and proinflammatory tumor necrosis factor-alpha (TNF-alpha) as well as interleukin-6 (IL-6) production in macrophages; moreover, application of synthetic antagonist, LP-17 polypeptide, reduced IL-6 production upon oxLDL stimulation in vitro and in vivo. In conclusion, in macrophages, oxLDL enhanced expression of TREM-1, which amplifies the innate immune response of TLR pathway; activation of TREM-1 contributes to atherogenesis process by enhancing proinflammatory cytokine production and foam cell formation. PMID- 26277358 TI - Optic pathway glioma in children: does visual deficit correlate with radiology in focal exophytic lesions? AB - PURPOSE: Unlike pilocytic astrocytomas in other parts of the brain, optic pathway gliomas (OPG) are usually diffuse lesions involving the anterior optic pathways and hypothalamus. Their infiltrative nature often precludes complete surgical resection. We sought to determine whether careful magnetic resonance (MR) analysis, correlated with visual deficits, could be sufficient to identify those focal lesions that may be amenable to more aggressive surgical resection at presentation. METHODS: We retrospectively reviewed the medical records of patients from two sites: children under 20 years of age treated for OPG between 1985 and 2009 at St Jude's Children's Research Hospital and children under 16 years of age treated at Great Ormond Street Hospital, London, UK, between 1984 and 2011. Patients with isolated optic nerve tumors were excluded. Visual acuity and visual field data at presentation were reviewed and correlated with MR characteristics, including extent of optic pathway involvement, symmetry, and lateral extension. RESULTS: Two hundred and one children were treated for OPG between 1984 and 2011 in the two institutions; 74 had neurofibromatosis 1 (NF1). At presentation, visual loss was symmetrical in 132 patients and asymmetrical in 69. Potential correlation between pattern of visual loss and tumor characteristics on routine MRI was found in only 13 patients with asymmetrical vision. There was no difference between patients with and without NF1. CONCLUSION: The decision for aggressive surgical resection for optic pathway gliomas should be based on clinical criteria, particularly in children with good vision in one eye and poor vision in the other, as current MRI results do not reliably predict visual field deficits. PMID- 26277359 TI - Familial moyamoya disease in two Turkish siblings with same polymorphism in RNF213 gene but different clinical features. AB - BACKGROUND: Moyamoya disease is an uncommon, progressive, and occlusive cerebrovascular disorder, predominantly affecting the terminal segment of the internal carotid arteries and its main branches. This occlusion results at the formation of a compensatory collateral arterial network (moyamoya vessels) developing at the base of the brain. The c.14576G>A variant in ring finger protein 213 (RNF213) was recently reported as a susceptibility gene for moyamoya disease. METHODS: We describe two Turkish pediatric siblings with moyamoya disease born to consanguineous, unaffected Turkish parents. RESULTS: The first patient (proband) is a 2-year-old boy who presented with afebrile focal seizures, moderate psychomotor retardation, paresis in the left upper and lower extremity, multiple infarctions of the brain, stenosis of the bilateral internal carotid artery and the middle cerebral artery, and stenosis of the right posterior cerebral artery. The second patient is a 10-year-old girl who is an elder sister of proband. She showed normal psychomotor development, millimetric signal enhancement without diffusion limitation of the brain, and stenosis of the bilateral internal carotid artery. CONCLUSION: We herein report pediatric sibling patients of moyamoya disease who have homozygous wild-type c.14576G>A variant in RNF213, showing different clinical course and disease severity. This is the first report of pediatric siblings with moyamoya disease from Turkey validating the genetic background of most frequent variant in East Asian patients with moyamoya disease. PMID- 26277360 TI - Syringomyelia following surgery for a spontaneous spinal subdural hematoma in a 13-year-old girl with congenital von Willebrand disease: case report and literature review. AB - BACKGROUND AND IMPORTANCE: Spontaneous spinal subdural hematomas are rare. Their occurrence in a child with congenital von Willebrand disease and the complication of their surgery by a large secondary syringomyelia have never been previously reported. CASE PRESENTATION: A 13-year-old girl with congenital von Willebrand disease presented to our emergency department in January 2011 for sudden onset of severe back pain centered in her thoracic spine rapidly aggravated by signs of acute myelopathy without any precipitating factor. MRI scan revealed a thoracic subdural collection anterior to the spinal cord at the T7-T9 level, hyperintense on T1- and T2-weighted sequences consistent with an acute spinal subdural hemorrhage. Evacuation of the subdural hematoma was realized immediately after hemostasis parameter correction, and post-operative course was uneventful with full functional recovery. One year later, the patient presented once again but with progressive and more severe myelopathy caused by a large syringomyelia extending from the T5 level to the conus medullaris. A syringopleural shunting was performed and the patient was unrolled under an intensive care and rehabilitation program. Her condition remarkably improved and she became able to walk independently within 2 weeks post-operatively. CONCLUSIONS: von Willebrand disease should be included as a possible factor of spontaneous spinal subdural hemorrhage. Surgery is advised in emergency and can be associated with remarkable recovery especially in children. Delayed syringomyelia can complicate the post operative course and can be successfully addressed by syringopleural shunting. Long-term clinical and radiological follow-up is advocated. PMID- 26277361 TI - Changing contraindications for t-PA in acute stroke: review of 20 years since NINDS. AB - When intravenous (IV) tissue-type plasminogen activator (t-PA) was originally approved by the Food and Drug Administration (FDA) for acute ischemic stroke (AIS) in 1996, there was a lengthy list of contraindications. In the 19 years since the approval of t-PA for AIS, it has been used off label and in patients with those contraindications. In February 2015, the list of contraindications for IV t-PA in AIS was revised and several of the previous contraindications were removed. As only 4 % of patients with ischemic stroke receive treatment with IV t PA, these changes increase the number of patients eligible for treatment. Anytime there is a significant change in the indications and treatment paradigm with a medication, there can be some resistance to the adaptation of the change into physician's treating habits. We seek to review what the changes to t-PA contraindications are, how they came about, as well as the literature on the previously off-label and currently off-label use of IV t-PA for patients with AIS. PMID- 26277363 TI - Optimal treatment of extracranial carotid artery disease: carotid endarterectomy, carotid stenting, or optimal medical therapy. AB - The optimal treatment of extracranial carotid artery disease is more controversial for asymptomatic than for symptomatic patients. Early trials comparing carotid endarterectomy to medical therapy alone demonstrated clear benefit of surgery in both symptomatic and asymptomatic populations. However, some believe that advances in medical therapy now lead to similar outcomes with optimal medical therapy alone and revascularization in asymptomatic patients. The role of carotid stenting is heavily debated, and the evidence base comparing carotid stenting to endarterectomy is limited primarily by inadequate operator experience as well as paucity of data in high surgical risk patients. A useful clinical approach to carotid bifurcation disease is to categorize patients by symptomatic status and revascularization risk. For symptomatic patients, revascularization should be favored over medical therapy alone. For asymptomatic patients, medical therapy alone might be considered, particularly for patients at high risk of revascularization and with anticipated survival <3-5 years. PMID- 26277362 TI - Management of depression after myocardial infarction. AB - Depression in patients who have had a myocardial infarction is an important clinical problem because it is extremely common and because the comorbidity complicates depression treatment and worsens the cardiovascular prognosis. Studies of psychotherapy, exercise, pharmacotherapy, and collaborative care demonstrate that effective treatment of depression is possible but the strength of the effects seen in most studies is low, and cardiovascular and all-cause morbidity and mortality benefits have not been proven. Recent collaborative care studies have had promising outcomes. For pharmacotherapy, side effects, including bleeding and arrhythmia risks, require special attention. Recovery from depression is associated with better long-term cardiovascular prognosis, while treatment per se is not. PMID- 26277364 TI - Stroke: advances in medical therapy and acute stroke intervention. AB - Evidence-based therapeutic options for stroke continue to emerge based on results from well-designed clinical studies. Ischemic stroke far exceeds hemorrhagic stroke in terms of prevalence and incidence, both in the USA and worldwide. The public health effect of reducing death and disability related to ischemic stroke justifies the resources that have been invested in identifying safe and effective treatments. The emergence of novel oral anticoagulants for ischemic stroke prevention in atrial fibrillation has introduced complexity to clinical decision making for patients with this common cardiac arrhythmia. Some accepted ischemic stroke preventative strategies, such as carotid revascularization for asymptomatic carotid stenosis, require reassessment, given advances in risk factor management, antithrombotic therapy, and surgical techniques. Intra arterial therapy, particularly with stent retrievers after intravenous tissue plasminogen activator, has recently been demonstrated to improve functional outcomes and will require investment in system-based care models to ensure that effective treatments are received by patients in a timely fashion. The purpose of this review is to describe recent advances in medical and surgical approaches to ischemic stroke prevention and acute treatment. Results from recently published clinical trials will be highlighted along with ongoing clinical trials addressing key questions in ischemic stroke management and prevention where equipoise remains. PMID- 26277365 TI - Can a closed carotid artery be reopened? AB - Carotid occlusion is a disease that presents a difficult decision for the treating provider. Traditionally, many providers would opt for expectant management with risk factor reduction and supportive therapy. There is a growing body of literature however pointing to possible improved outcomes of more aggressive treatments, including reopening of the occluded carotid. In this review, we discuss the difficulties involved in diagnosing a patient presenting with symptomatic carotid occlusion, the natural history of the disease, and the emerging treatment options and paradigms of different institutions based on recent literature. PMID- 26277366 TI - Intra-arterial thrombectomy: does invasive treatment lead to better outcomes than intravenous thrombolysis alone? AB - Intravenous thrombolysis is considered to be standard of care for acute ischemic stroke patients arriving within 3-4.5 h of stroke symptom onset. Recently, endovascular therapies have been proposed to extend and enhance stroke outcomes by targeting large vessel occlusions. Different radiologic methods, time windows, and treatment tools have delineated differences between trials. Overall, intravenous thrombolysis remains the treatment of choice for all acute ischemic stroke patients, with a small subset benefiting from additional endovascular therapy. Endovascular therapy remains a viable singular option for patients with large vessel occlusion unable to receive thrombolysis. PMID- 26277368 TI - Sudden infant death due to Lactococcal infective endocarditis. AB - Infective endocarditis (IE) of infants is rare, most of which occur associated with congenital heart disease or its cardiac surgery. We experienced a case of sudden death of a four-month-old male infant without congenital heart disease. It was elucidated by postmortem examination that the dead had suffered severe IE, which led him to death. In the microbiological genetic analysis using histological section, the pathogen causing inflammation in the present case was identified as Lactococcus lactis subspecies, although Staphylococci have been reported to be common and important one. Previously reported infectious diseases by Lactococcus lactis subspecies were all adult cases and this is the first report of an infantile death due to Lactococcal IE according to our knowledge. Any fatal disease may be included in sudden death cases targeted for forensic autopsy, even if it is rare. It is expected for forensic pathologists that they note such case and share each experience among themselves and other medical fields to develop a strategy for prevention. PMID- 26277367 TI - Depression in people with coronary heart disease: prognostic significance and mechanisms. AB - Depression affects about 40 % of people with coronary heart disease (CHD). This group with depression and CHD have increased mortality and morbidity, worse health-related quality of life, use health services more frequently and consequently cost the health service and the national economy considerably more than their non-depressed counterparts. A number of characteristics of depression and plausible mechanisms have been proposed to explain this observed association, which could lead to improved understanding of the association and lead to new interventions to improve cardiac outcomes. This review summarises the evidence linking depression with worse cardiac outcomes, considers specific aspects of depression which may predict worse outcomes and reviews the mechanisms that could potentially explain the direct or indirect association of depression with coronary outcomes. PMID- 26277369 TI - An assessment of the relevance of the home neighbourhood for understanding environmental influences on physical activity: how far from home do people roam? AB - BACKGROUND: The choice of geographical unit of analysis in studies of the built environment and physical activity has typically been restricted to the home neighbourhood where only a small proportion of physical activity may actually be undertaken. This study aimed to examine the distance from home at which physical activity takes place and how this varies by personal and neighbourhood characteristics. METHODS: A cross-sectional, population based study of 195 people in the North West region of England, aged 18 to 91 years, clustered in 60 localities (small geographical areas of ~125 households). Individual socio demographic data were collected by computer-aided personal interviews and physical activity was characterised by accelerometer and Global Positioning System (GPS) data. The locations of periods of light, moderate and vigorous intensity physical activity (LMVPA) undertaken outdoors were linked to measures of the neighbourhood around the home and distance from home. RESULTS: Sixty per cent of outdoors LMVPA took place outside of the proximal home neighbourhood (800 m buffer). Distances from home where median levels of LMVPA were undertaken varied by gender (p < 0.05), home location, area deprivation, and car ownership (all p < 0.001). CONCLUSIONS: Objectively measured physical activity appears to vary appreciably by participant characteristics and home location, although for many settings a large proportion is undertaken outside of the home neighbourhood, suggesting the characterisation of neighbourhoods close to home will fail to properly capture the environmental influences on physical activity. PMID- 26277370 TI - Clarifying hierarchical age-period-cohort models: A rejoinder to Bell and Jones. AB - Previously, Reither et al. (2015) demonstrated that hierarchical age-period cohort (HAPC) models perform well when basic assumptions are satisfied. To contest this finding, Bell and Jones (2015) invent a data generating process (DGP) that borrows age, period and cohort effects from different equations in Reither et al. (2015). When HAPC models applied to data simulated from this DGP fail to recover the patterning of APC effects, B&J reiterate their view that these models provide "misleading evidence dressed up as science." Despite such strong words, B&J show no curiosity about their own simulated data--and therefore once again misapply HAPC models to data that violate important assumptions. In this response, we illustrate how a careful analyst could have used simple descriptive plots and model selection statistics to verify that (a) period effects are not present in these data, and (b) age and cohort effects are conflated. By accounting for the characteristics of B&J's artificial data structure, we successfully recover the "true" DGP through an appropriately specified model. We conclude that B&Js main contribution to science is to remind analysts that APC models will fail in the presence of exact algebraic effects (i.e., effects with no random/stochastic components), and when collinear temporal dimensions are included without taking special care in the modeling process. The expanded list of coauthors on this commentary represents an emerging consensus among APC scholars that B&J's essential strategy--testing HAPC models with data simulated from contrived DGPs that violate important assumptions--is not a productive way to advance the discussion about innovative APC methods in epidemiology and the social sciences. PMID- 26277371 TI - Supercritical fluid precipitation of ketoprofen in novel structured lipid carriers for enhanced mucosal delivery--a comparison with solid lipid particles. AB - Structured lipid carriers based on mixture of solid lipids with liquid lipids are the second generation of solid lipid particles, offering the advantage of improved drug loading capacity and higher storage stability. In this study, structured lipid carriers were successfully prepared for the first time by precipitation from gas saturated solutions. Glyceryl monooleate (GMO), a liquid glycerolipid, was selected in this work to be incorporated into three solid glycerolipids with hydrophilic-lipophilic balance (HLB) ranging from 1 to 13, namely Gelucire 43/01TM, GeleolTM and Gelucire 50/13TM. In general, microparticles with a irregular porous morphology and a wide particle size distribution were obtained. The HLB of the individual glycerolipids might be a relevant parameter to take into account during the processing of solid:liquid lipid blends. As expected, the addition of a liquid lipid into a solid lipid matrix led to increased stability of the lipid carriers, with no significant modifications in their melting enthalpy after 6 months of storage. Additionally, Gelucire 43/01TM:GMO particles were produced with different mass ratios and loaded with ketoprofen. The drug loading capacity of the structured lipid carriers increased as the GMO content in the particles increased, achieving a maximum encapsulation efficiency of 97% for the 3:1 mass ratio. Moreover, structured lipid carriers presented an immediate release of ketoprofen from its matrix with higher permeation through a mucous-membrane model, while solid lipid particles present a controlled release of the drug with less permeation capacity. PMID- 26277372 TI - TET2 expression level and 5-hydroxymethylcytosine are decreased in refractory cytopenia of childhood. AB - Myelodysplastic syndromes (MDS) are myeloid malignancies characterized by ineffective hematopoiesis, dysplasia, peripheral cytopenia and increased risk of progression to acute myeloid leukemia. Refractory cytopenia of childhood (RCC) is the most common subtype of pediatric MDS and has overlapping clinical features with viral infections and autoimmune disorders. Mutations in TET2 gene are found in about 20-25% of adult MDS and are associated with a decrease in 5 hydroxymethylcytosine (5-hmC) content. TET2 deregulation and its malignant potential were reported in adult but not in pediatric MDS. We evaluated the gene expression and the presence of mutations in TET2 gene in 19 patients with RCC. TET2 expression level was correlated with 5-hmC amount in DNA and possible regulatory epigenetic mechanisms. One out of 19 pediatric patients with RCC was a carrier of a TET2 mutation. TET2 expression and 5-hmC levels were decreased in patients when compared to a disease-free group. Lower expression was not associated to the presence of mutation or with the status of promoter methylation, but a significant correlation with microRNA-22 expression was found. These findings suggested that TET2 downregulation and low levels of 5-hmC are inversely related to miR-22 expression. The existence of a regulatory loop between microRNA-22 and TET2 may play a role in MDS pathogenesis. PMID- 26277373 TI - Endoscopic Full-Thickness Resection of an Inverted Colonic Diverticulum With Intraepithelial Neoplasia Using the Ligate-and-Let-Go Technique. PMID- 26277374 TI - Development and validation of a novel tool for assessing pitch discrimination. AB - OBJECTIVE: To develop and validate a tool for pitch discrimination that can be easily applied in otolaryngology clinics. METHODS: Twenty healthy subjects performed three psychoacoustic tasks for assessing pitch discrimination thresholds, which were compared among the three tasks. In the pitch direction discrimination (PDirD) task, the subjects judged the pitch of two tones as higher or lower. In the pitch difference discrimination (PDiffD) task, the subjects judged the pitch of two tones as same or different. In the pitch pattern detection (PPD) task, the subjects judged the pattern of a tone complex. Using tone sets from level 0 to level 8, pitch thresholds were determined using the Parameter Estimation by Sequential Testing (PEST) staircase procedure. The tasks were performed without prior training. RESULTS: Every test was performed twice for each ear, and the better results were adopted as the threshold values. The PDirD thresholds varied considerably among the subjects and showed significantly larger deviations relative to those of the PPD thresholds. The number of below 0 thresholds, which are considered inadequate results, was significantly larger in the PDiffD task. In the PPD task, all thresholds except one were above level 6. The average total time taken to complete the PPD task was 7.7min, which was significantly lesser than that taken to complete the other two tasks. CONCLUSION: The results of our study suggest that the PPD task is a reliable and easily available tool for the assessment of pitch discrimination. PMID- 26277375 TI - Hearing loss in postmenopausal women with low bone mineral density. AB - OBJECTIVE: Several studies suggested the possible relationship between decreased bone mineral density (BMD) of the temporal bone and hearing loss, primarily of the sensorineural type. The aim of the present study is to determine the relationship between BMD and hearing loss and to evaluate the systemic Ca(2+) and vitamin D status with relation to hearing sensitivity in the postmenopausal women who were diagnosed with primary osteoporosis. METHODS: The study involved a total of 324 patients who were referred between 2008 and 2013. Based on BMD scores, the subjects were divided into three groups: normal BMD (n=102), osteopenia (n=106) and osteoporosis (n=116). Hearing sensitivity was evaluated with audiometric tests along with serum Ca(2+) and vitamin D level. RESULTS: The age distribution among 3 groups was similar. Mean serum Ca(2+), phosphate, 25(OH)D and creatinine clearance were within the standard laboratory reference ranges in all patients. There was no difference in the proportion of vitamin D deficiency among groups. The typical type of hearing loss was sensorineural hearing loss (SNHL) and the patients with reduced BMD showed higher prevalence of SNHL than the patients with normal BMD. Pure-tone thresholds average was significantly higher in all frequencies in women with osteopenia/osteoporosis than women with normal BMD. Multiple logistic regression analyses showed that age and lumbar BMD were associated with the presence of hearing loss (>25dB). CONCLUSION: Our findings suggest that the presence of decreased BMD in postmenopausal women might be associated with the higher prevalence of age-related SNHL. PMID- 26277376 TI - Rapid-scan coherence signals in X-band EPR spectra of semiquinones with small hyperfine splittings. AB - Rapid-scan EPR signals for semiquinones with very-small well-resolved hyperfine splittings exhibit coherence signals at a time after passing through the EPR line that is proportional to the reciprocal of the hyperfine splitting. Such coherences are a general phenomenon due to constructive interference of the responses to transient excitation of spins by rapid scan of the magnetic field across equally spaced spin packets. Examples are shown for 2,3,5,6-tetramethoxy 1,4-benzosemiquinone with aH=46 mG for 12 protons and for 2,5-di-t-butyl-1,4 benzosemiquinone with aH=59 mG for 18 protons. PMID- 26277377 TI - Degree of bioresorbable vascular scaffold expansion modulates loss of essential function. AB - Drug-eluting bioresorbable vascular scaffolds (BVSs) have the potential to restore lumen patency, enable recovery of the native vascular environment, and circumvent late complications associated with permanent endovascular devices. To ensure therapeutic effects persist for sufficient times prior to scaffold resorption and resultant functional loss, many factors dictating BVS performance must be identified, characterized and optimized. While some factors relate to BVS design and manufacturing, others depend on device deployment and intrinsic vascular properties. Importantly, these factors interact and cannot be considered in isolation. The objective of this study is to quantify the extent to which degree of radial expansion modulates BVS performance, specifically in the context of modifying device erosion kinetics and evolution of structural mechanics and local drug elution. We systematically varied degree of radial expansion in model BVS constructs composed of poly dl-lactide-glycolide and generated in vitro metrics of device microstructure, degradation, erosion, mechanics and drug release. Experimental data permitted development of computational models that predicted transient concentrations of scaffold-derived soluble species and drug in the arterial wall, thus enabling speculation on the short- and long-term effects of differential expansion. We demonstrate that degree of expansion significantly affects scaffold properties critical to functionality, underscoring its relevance in BVS design and optimization. STATEMENT OF SIGNIFICANCE: Bioresorbable vascular scaffold (BVS) therapy is beginning to transform the treatment of obstructive artery disease, owing to effective treatment of short term vessel closure while avoiding long term consequences such as in situ, late stent thrombosis - a fatal event associated with permanent implants such as drug eluting stents. As device scaffolding and drug elution are temporary for BVS, the notion of using this therapy in lieu of existing, clinically approved devices seems attractive. However, there is still a limited understanding regarding the optimal lifetime and performance characteristics of erodible endovascular implants. Several engineering criteria must be met and clinical endpoints confirmed to ensure these devices are both safe and effective. In this manuscript, we sought to establish general principles for the design and deployment of erodible, drug-eluting endovascular scaffolds, with focus on how differential expansion can modulate device performance. PMID- 26277378 TI - Highly adjustable biomaterial networks from three-armed biodegradable macromers. AB - Biocompatible material platforms with adjustable properties and option for chemical modification are warranted for site-specific biomedical applications. To this end, three-armed biodegradable macromers of well-defined chemical characteristics were prepared from trivalent alcohols with different degrees of ethoxylation and different lengths of oligoester domains. A platform of 15 different macromers was established. The macromers were designed to exhibit different hydrophilicities and molecular weights and contained various types of oligoesters such as d,l-lactide, l-lactide and epsilon-caprolactone. Macromers chemical composition was determined and molecular weights ranged from 900 to 3000 Da. Thermally induced cross-linking of methacrylated macromers was monitored by oscillation rheology. A novel variant of the solid lipid templating technique was established to fabricate macroporous tissue engineering scaffolds from these macromers. Scaffold properties were thoroughly investigated regarding mechanical properties, compositional analysis including methacrylic double bond conversion, microstructure and porosity. Material properties could be controlled by macromer chemistry. By variation of the fabrication procedure and processing parameters scaffold porosity was increased up to 88%. Basic cytocompatibility was assessed including indirect and direct contact methods. The established macromers hold promise for various biomedical purposes. STATEMENT OF SIGNIFICANCE: Specific biomedical applications require tailored biomaterials with defined properties. We established a macromer platform for preparation of tissue engineering scaffolds with adjustable chemical and mechanical characteristics. Macromers were composed of trivalent core alcohols with different degrees of ethoxylation to which biodegradable domains - lactide or epsilon-caprolactone - were oligomerized before final methacrylation. The solid lipid templating technique was adapted to fabricate macroporous scaffolds with controlled pore structure and porosity from the developed macromers, which can also be processed by solid freeform fabrication techniques. The material platform relies on clinically established chemistries of the biodegradable domains and the macromer concept enables the fabrication of networks in which cross-polymerization kinetics, mechanical properties and surface hydrophobicity is predefined by macromer chemistry. Cytocompatibility was confirmed by indirect and direct cell contact experiments. PMID- 26277379 TI - Regulating myogenic differentiation of mesenchymal stem cells using thermosensitive hydrogels. AB - Stem cell therapy has potential to regenerate skeletal muscle tissue in ischemic limb. However, the delivered stem cells experience low rate of myogenic differentiation. Employing injectable hydrogels as stem cell carriers may enhance the myogenic differentiation as their modulus may be tailored to induce the differentiation. Yet current approaches used to manipulate hydrogel modulus often simultaneously vary other properties that also affect stem cell differentiation, such as chemical structure, composition and water content. Thus it is challenging to demonstrate the decoupled effect of hydrogel modulus on stem cell differentiation. In this report, we decoupled the hydrogel modulus from chemical structure, composition, and water content using injectable and thermosensitive hydrogels. The hydrogels were synthesized from N-isopropylacrylamide (NIPAAm), acrylic acid (AAc), and degradable macromer 2-hydroxyethyl methacrylate-oligomer [oligolatide, oligohydroxybutyrate, or oligo(trimethylene carbonate)]. We found that using the same monomer composition and oligomer chemical structure but different oligomer length can independently vary hydrogel modulus. Rat bone marrow mesenchymal stem cells (MSCs) were encapsulated in the hydrogels with elastic expansion moduli of 11, 20, and 40 kPa, respectively. After 14 days of culture, significant myogenic differentiation was achieved for the hydrogel with elastic expansion modulus of 20 kPa, as judged from both the gene and protein expression. In addition, MSCs exhibited an elastic expansion modulus-dependent proliferation rate. The most significant proliferation was observed in the hydrogel with elastic expansion modulus of 40 kPa. These results demonstrate that the developed injectable and thermosensitive hydrogels with suitable modulus has the potential to deliver stem cells into ischemic limb for enhanced myogenic differentiation and muscle regeneration. STATEMENT OF SIGNIFICANCE: Stem cell therapy for skeletal muscle regeneration in ischemic limb experiences low rate of myogenic differentiation. Employing injectable hydrogels as stem cell carriers may enhance the myogenic differentiation as hydrogel modulus may be modulated to induce the differentiation. Yet current approaches used to modulate hydrogel modulus may simultaneously vary other properties that also affect stem cell myogenic differentiation, such as chemistry, composition and water content. In this report, we decoupled the hydrogel modulus from chemistry, composition, and water content using injectable and thermosensitive hydrogels. We found that mesenchymal stem cells best differentiated into myogenic lineage in the hydrogel with elastic modulus of 20 kPa. PMID- 26277380 TI - Early glycaemic control in metformin users receiving their first add-on therapy: a population-based study of 4,734 people with type 2 diabetes. AB - AIMS/HYPOTHESIS: The aims of this work were to assess glycaemic control in metformin users receiving their first add-on glucose-lowering therapy and to examine the real-life effectiveness of different add-on drugs. METHODS: We carried out a population-based cohort study using healthcare databases in northern Denmark during 2000-2012. We included 4,734 persons who initiated metformin monotherapy and added another glucose-lowering drug within 3 years. Attainment of recommended HbA1c goals within 6 months of add-on was investigated, using Poisson regression analysis adjusted for age, sex, baseline HbA(1c), diabetes duration, complications and Charlson Comorbidity Index. RESULTS: Median metformin treatment duration at intensification was 12 months (interquartile range [IQR] 4-23 months) and pre-intensification HbA(1c) was 8.0% (IQR 7.2-9.2%) (64 [IQR 55-77] mmol/mol). Median HbA(1c) dropped 1.2% (13 mmol/mol) with a sulfonylurea (SU) add-on, 0.8% (9 mmol/mol) with a dipeptidyl peptidase-4 (DPP-4) inhibitor, 1.3% (14 mmol/mol) with a glucagon-like peptide-1 (GLP-1) receptor agonist, 0.9% (10 mmol/mol) with other non-insulin drugs and 2.4% (26 mmol/mol) with insulin. Compared with SU add-on, attainment of HbA(1c) <7% (<53 mmol/mol) was higher with GLP-1 receptor agonists (adjusted RR [aRR] 1.10; 95% CI 1.01, 1.19) and lower with DPP-4 inhibitors (aRR 0.94; 95% CI 0.89, 0.99), other drugs (aRR 0.86; 95% CI 0.77, 0.96) and insulin (aRR 0.88; 95% CI 0.77, 0.99). The proportion of metformin add-on users who attained HbA(1c) <7% (<53 mmol/mol) increased from 46% in 2000-2003 to 59% in 2010-2012, whereas attainment of HbA(1c) <6.5% (<48 mmol/mol) remained 30% among patients aged <65 years without comorbidities. CONCLUSIONS/INTERPRETATION: Among early type 2 diabetes patients receiving their first metformin add-on treatment, HbA(1c) reduction with different non-insulin drugs is similar to, and comparable with, that observed in randomised trials, yet 41% do not achieve HbA(1c) <7% (<53 mmol/mol) within 6 months. PMID- 26277382 TI - The use of a detachable multiple polyp catcher to facilitate accurate location and pathological diagnosis of resected polyps in the proximal colon. PMID- 26277381 TI - Plasma fatty acids as predictors of glycaemia and type 2 diabetes. AB - AIMS/HYPOTHESIS: Our aim was to investigate the fasting proportions of fatty acids and estimated desaturase and elongase activities in three different lipid fractions in plasma, phospholipids (PLs), cholesteryl esters (CEs) and triacylglycerols (TGs), as predictors for the worsening of glycaemia (area under the glucose curve in an OGTT [glucose AUC]) and incident type 2 diabetes in a 5.9 year follow-up of the Metabolic Syndrome in Men population-based cohort. METHODS: Fatty acid proportions were measured in plasma PL, CE and TG fractions in 1,364 Finnish men aged 45-68 years at baseline. The prospective follow-up study included only men who were non-diabetic at baseline and had data available at follow-up (n = 1,302). A total of 71 participants developed new type 2 diabetes during follow-up. RESULTS: After adjusting for confounding factors, total saturated fatty acids, palmitoleic acid (16:1n-7), dihomo-gamma-linolenic acid (20:3n-6) and estimated stearoyl-CoA desaturase 1 and Delta(6)-desaturase (D6D) enzyme activities significantly predicted the worsening of glycaemia whereas total polyunsaturated fatty acid, linoleic acid (18:2n-6) and elongase activity predicted a decrease in the glucose AUC. Estimated D6D activity and dihomo-gamma linolenic acid (20:3n-6) were associated with an increased risk of incident type 2 diabetes. Results were consistent across the three different lipid fractions. However, fatty acid proportions in the PL and CE fractions were stronger predictors for glycaemia and incident type 2 diabetes compared with fatty acid proportions in the TG fraction. CONCLUSIONS/INTERPRETATION: Selected fatty acid proportions of plasma lipid fractions and their ratios, which reflect desaturase and elongase enzyme activities, may be good biomarkers for the worsening of glycaemia and incident type 2 diabetes. PMID- 26277383 TI - Nicotinic receptors modulate the function of presynaptic AMPA receptors on glutamatergic nerve terminals in the trigeminal caudal nucleus. AB - In this study, we demonstrate the existence on trigeminal caudal nucleus (TCN) glutamatergic terminals of alpha4beta2 nicotinic receptors (nAChRs) capable of enhancing the terminals' spontaneous release of [(3)H]d-aspartate ([(3)H]D-Asp). In rat TCN synaptosomes, spontaneous [(3)H]D-Asp release was increased by nicotine and the nicotinic receptor agonists (+/-)epibatidine and RJR2403. The increase was potentiated by the positive allosteric modulator of nAChRs LY2087101, inhibited by the nicotinic antagonists mecamylamine (MEC) and dihydro beta-erythroidine hydrobromide (DHbetaE), and unaffected by alpha-bungarotoxin (alpha-BgTx) and methyllycaconitine (MLA). Evidence of functional interaction was observed between the alpha4beta2 nAChRs and cyclothiazide-sensitive, alfa-amino-3 hydroxy-5-methyl-4-isoxazolone propionate (AMPA) receptors co-localized on the TCN synaptosomes. Brief pre-exposure of synaptosomes to 30 MUM nicotine or 10 MUM RJR2403 abolished the AMPA (100 MUM) -induced potentiation of [K(+)]e-evoked [(3)H]D-Asp release, an effect that seems to be caused by nicotine-induced increases in the internalization of AMPA receptors. Indeed, the effects of nicotine-pretreatment were not seen in synaptosomes containing pre-entrapped pep2 SVKI, a peptide known to compete for the binding of GluA2 subunit to scaffolding proteins involved in AMPA endocytosis, while entrapment of pep2-SVKE, an inactive peptide used as negative control, was inefficacious. These findings show that nicotine can negatively modulate the function of AMPA receptors present on glutamatergic nerve terminals in the rat TCN. Dynamic control of AMPA receptors by the nicotinic cholinergic system has been observed under other experimental conditions, and it can contribute to the control of synaptic plasticity such as long-term depression and potentiation. Nicotine's ability to reduce the functionality of presynaptic AMPA receptors could contribute to its analgesic effects by diminishing glutamatergic transmission from the primary afferent terminals that convey nociceptive input to TCN. PMID- 26277385 TI - Imaging features of complex solid and multicystic ovarian lesions: proposed algorithm for differential diagnosis. AB - Complex solid and multicystic ovarian lesions are broad-spectrum diseases, ranging from benign to malignant. This article describes the broad-spectrum and imaging features of complex solid and multicystic ovarian lesions and illustrates an algorithmic approach to such lesions, focusing on the ultrasonography and magnetic resonance imaging features that allow one to hone the differential diagnosis. Multimodality imaging workup plays an important role in the characterization and differential diagnosis of these diseases. Also, knowledge of the clinical setting and imaging features for the spectrum of complex solid and multicystic ovarian lesions can lead to appropriate management. PMID- 26277384 TI - Resveratrol neuroprotection in stroke and traumatic CNS injury. AB - Resveratrol, a stilbene formed in many plants in response to various stressors, elicits multiple beneficial effects in vertebrates. Particularly, resveratrol was shown to have therapeutic properties in cancer, atherosclerosis and neurodegeneration. Resveratrol-induced benefits are modulated by multiple synergistic pathways that control oxidative stress, inflammation and cell death. Despite the lack of a definitive mechanism, both in vivo and in vitro studies suggest that resveratrol can induce a neuroprotective state when administered acutely or prior to experimental injury to the CNS. In this review, we discuss the neuroprotective potential of resveratrol in stroke, traumatic brain injury and spinal cord injury, with a focus on the molecular pathways responsible for this protection. PMID- 26277386 TI - Urban air quality comparison for bus, tram, subway and pedestrian commutes in Barcelona. AB - Access to detailed comparisons in air quality variations encountered when commuting through a city offers the urban traveller more informed choice on how to minimise personal exposure to inhalable pollutants. In this study we report on an experiment designed to compare atmospheric contaminants inhaled during bus, subway train, tram and walking journeys through the city of Barcelona. Average number concentrations of particles 10-300 nm in size, N, are lowest in the commute using subway trains (N<2.5*10(4) part. cm(-3)), higher during tram travel and suburban walking (2.5*10(4) cm(-3)5.0*10(4) cm(-3)), with extreme transient peaks at busy traffic crossings commonly exceeding 1.0*10(5) cm(-3) and accompanied by peaks in Black Carbon and CO. Subway particles are coarser (mode 90 nm) than in buses, trams or outdoors (<70 nm), and concentrations of fine particulate matter (PM2.5) and Black Carbon are lower in the tram when compared to both bus and subway. CO2 levels in public transport reflect passenger numbers, more than tripling from outdoor levels to >1200 ppm in crowded buses and trains. There are also striking differences in inhalable particle chemistry depending on the route chosen, ranging from aluminosiliceous at roadsides and near pavement works, ferruginous with enhanced Mn, Co, Zn, Sr and Ba in the subway environment, and higher levels of Sb and Cu inside the bus. We graphically display such chemical variations using a ternary diagram to emphasise how "air quality" in the city involves a consideration of both physical and chemical parameters, and is not simply a question of measuring particle number or mass. PMID- 26277387 TI - Renal phenotype of young and old telomerase-deficient mice. AB - Telomere shortening in the kidney explains the impaired regenerative capacity, but may not drive the ageing phenotype itself. We investigated kidneys from young and old Terc(+/+) and Terc(-/-) mice of early (G1) and late (G4, G5) generations. Functional parameters declined and age-related morphological changes increased in late generation Terc(-/-) mice and with further age. Podocyte loss was only seen in old G4 Terc(-/-). Whereas p21(CIP1/WAF1) was highest in old G1 and G4 Terc(-/ ), telomere shortening and p16(INK4a) expression, also significantly associated with later generation young Terc(-/-), were not further induced in old Terc(-/-) mice. Both, young and old late generation Terc(-/-), showed increased pro inflammatory cytokine levels. Young late generation Terc(-/-) animals show mild functional and histological abnormalities, the presence of cellular senescence explains their kidneys' limited regenerative capacity. While these aspects resemble the situation seen in aged human kidneys, the lack of telomere shortening and p16(INK4a) induction in older Terc(-/-) animals differs from observations in old human kidneys and may result from clearance of senescent cells. This animal model is well suited to investigate the mechanisms of impaired renal regeneration in aged human kidney, but may not fully explain the natural course of the human renal ageing phenotype. PMID- 26277388 TI - Arf6 mediates Schwann cell differentiation and myelination. AB - During development of the peripheral nervous system (PNS), Schwann cells wrap neuronal axons, becoming the myelin sheaths that help axonal functions. While the intercellular signals controlling the myelination process between Schwann cells and peripheral neurons are well studied, the transduction of these signals in Schwann cells still remains elusive. Here, we show that Arf6, an Arf protein of the small GTPase family, is involved in promoting the myelination process. Knockdown of Arf6 with the small-interfering (si)RNA in primary Schwann cells markedly decreases dibutyl-cyclic AMP-induced myelin marker protein expression, indicating that Arf6 plays a role in differentiation-like phenotypic changes. To obtain in vivo evidence, we generated small-hairpin (sh)RNA transgenic mice targeting Arf6 for Schwann cells. Transgenic mice exhibited reduced myelin thickness compared to littermate controls, consistent with the defective myelin formation observed in the transgenic mouse-derived Schwann cell and neuronal culture system. Transgenic mice also exhibited decreased phosphorylation of myelination-related signaling molecules such as Akt kinase cascade proteins as well as downregulation of myelin marker proteins. These results suggest that signaling through Arf6 is required for Schwann cell myelination, adding Arf6 to the list of intracellular signaling molecules involved in the myelination process. PMID- 26277389 TI - Overexpression of acetylcholinesterase gene in rice results in enhancement of shoot gravitropism. AB - Acetylcholine (ACh), a known neurotransmitter in animals and acetylcholinesterase (AChE) exists widely in plants, although its role in plant signal transduction is unclear. We previously reported AChE in Zea mays L. might be related to gravitropism based on pharmacological study using an AChE inhibitor. Here we clearly demonstrate plant AChE play an important role as a positive regulator in the gravity response of plants based on a genetic study. First, the gene encoding a second component of the ACh-mediated signal transduction system, AChE was cloned from rice, Oryza sativa L. ssp. Japonica cv. Nipponbare. The rice AChE shared high homology with maize, siratro and Salicornia AChEs. Similar to animal and other plant AChEs, the rice AChE hydrolyzed acetylthiocholine and propionylthiocholine, but not butyrylthiocholine. Thus, the rice AChE might be characterized as an AChE (E.C.3.1.1.7). Similar to maize and siratro AChEs, the rice AChE exhibited low sensitivity to the AChE inhibitor, neostigmine bromide, compared with the electric eel AChE. Next, the functionality of rice AChE was proved by overexpression in rice plants. The rice AChE was localized in extracellular spaces of rice plants. Further, the rice AChE mRNA and its activity were mainly detected during early developmental stages (2 d-10 d after sowing). Finally, by comparing AChE up-regulated plants with wild-type, we found that AChE overexpression causes an enhanced gravitropic response. This result clearly suggests that the function of the rice AChE relate to positive regulation of gravitropic response in rice seedlings. PMID- 26277390 TI - PEDF attenuates hypoxia-induced apoptosis and necrosis in H9c2 cells by inhibiting p53 mitochondrial translocation via PEDF-R. AB - Pigment epithelial-derived factor (PEDF) is a multifunctional secreted glycoprotein, which could protect against hypoxia-induced cell death related to its anti-oxidative effect in cultured cardiomyocytes. However, the pathway mediating this cytoprotective process has not been fully established. Here we confirmed that PEDF bound to pigment epithelial-derived factor receptor (PEDF-R) expressed on the membrane of H9c2 cells. Under hypoxic condition, PEDF increased the ratio of MDM2:p53, so as to inhibited p53 mitochondrial translocation via PEDF-R. As a result, mitochondrial outer membrane permeabilization (MOMP) and mitochondrial permeability transition pore (MPTP) opening were inhibited, meanwhile cleaved caspase-3, PARP and the release of HMGB1 were reduced. Accordingly, apoptosis and necrosis were attenuated simultaneously. We conclude that PEDF-R mediates PEDF attenuates hypoxia-induced apoptosis and necrosis in H9c2 cells by inhibiting p53 mitochondrial translocation. PMID- 26277391 TI - Deferoxamine attenuates lipopolysaccharide-induced inflammatory responses and protects against endotoxic shock in mice. AB - To examine the role of the intracellular labile iron pool (LIP) in the induction of inflammatory responses, we investigated the anti-inflammatory effect of the iron chelator deferoxamine (DFO) on lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 macrophage cells and endotoxic shock in mice in the present study. Our data showed that DFO significantly decreased LPS-induced LIP and ROS upregulation. We then found that DFO inhibited phosphorylation of MAP kinases such as ERK and p38 and also inhibited the activation of NF-kappaB induced by LPS. Furthermore, the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), nitric oxide (NO) and prostaglandin E2 (PGE2) induced by LPS was inhibited by DFO in RAW264.7 macrophages. Administration of DFO significantly decreased the mortality and improved the survival of septic mice with lethal endotoxemia in LPS-injected mice. These results demonstrate that iron plays a pivotal role in the induction of inflammatory responses and against septic shock. DFO has effective inhibitory effect on the production of inflammatory mediators via suppressing activation of MAPKs and NF-kappaB signaling pathways; it also has a protective effect on LPS-induced endotoxic shock in mice. Our findings open doors to further studies directed at exploring a new class of drugs against septic shock or other inflammatory diseases by modulating cellular chelatable iron. PMID- 26277392 TI - Nitration of indoxyl sulfate facilitates its cytotoxicity in human renal proximal tubular cells via expression of heme oxygenase-1. AB - Peroxynitrite, the reaction product of superoxide [Formula: see text] and nitric oxide (NO), nitrates tyrosine residues, unsaturated fatty acids, cyclic guanosine monophosphate and other phenolics. We report herein that indoxyl sulfate (IS) is also nitrated by peroxynitrite in vitro and forms 2-nitro-IS, as determined from spectral characteristics and (1)H-NMR. IS is one of the very important uremic toxins that accelerate the progression of chronic kidney disease via various mechanisms. However, cell viability experiments with human proximal tubular cells show that the cytotoxicity of 2-nitro-IS is several-fold higher than that of IS. The explanation for this finding seems to be that 2-nitro-IS induces a much more pronounced generation of intracellular reactive oxygen species (ROS) than IS. Results with inhibitors revealed that an organic anion transporter, several intracellular enzymes and nonprotein-bound iron ions are reasons for this finding. Most importantly, however, as detected by immunofluorescence and Western blotting, 2-nitro-IS induces the expression of heme oxygenase-1 and thereby the formation of ROS; most probably through the Fenton reaction. The final result of the increased amounts of ROS is death of the kidney cells. Thus, nitration of uremic toxins by peroxynitrite may help us to understand the initiation and progress of chronic kidney diseases. PMID- 26277393 TI - Neuronal differentiation of human iPS cells induced by baicalin via regulation of bHLH gene expression. AB - Efficient differentiation is important for regenerative medicine based on pluripotent stem cells, including treatment of neurodegenerative disorders and trauma. Baicalin promotes neuronal differentiation of neural stem/progenitor cells of rats and mice. To evaluate the suitability of baicalin for neuronal differentiation of human iPS cells, we investigated whether it promotes neuronal differentiation in human iPS cells and monitored basic helix-loop-helix (bHLH) gene expression during neuronal differentiation. Baicalin promoted neuronal differentiation and inhibited glial differentiation, suggesting that baicalin can influence the neuronal fate decision in human iPS cells. Notch signaling, which is upstream of bHLH proteins, was not involved in baicalin-induced neuronal differentiation. Baicalin treatment did not down-regulate Hes1 gene expression, but it reduced Hes1 protein levels and up-regulated Ascl1 gene expression. Thus, baicalin promoted neuronal differentiation via modulation of bHLH transcriptional factors. Therefore, baicalin has potential to be used as a small-molecule drug for regenerative treatment of neurodegenerative disorders. PMID- 26277394 TI - Simple and sensitive electrochemical impedimetric approach towards analysis of biophysical interaction. AB - Study of biophysical interactions have been carried out using specific combination of proteins such as human IgG (as antigen) and anti-human IgG (as complementary antibody; raised in rabbit). Bovine serum albumin (BSA) was used to block any nonspecific interaction between antigen and antibody as BSA has been reported to bind to several sites non-specifically. Optimization of BSA concentration was done in order to make the antigen-antibody interaction relatively more pronounced and specific. We have used gold electrode in order to provide a relatively inert platform for adsorption/immobilization of protein molecules. The interaction between the antigen and antibody caused an increase in the charge transfer resistance (parallel resistance in Randles cell model) for an indicator molecule (hexacyanoferrate) and this was monitored by impedance spectroscopy. Detection limit for the antigen was found to be about 50 ng/mL. The approach presented is general and versatile and can be used for any antigen antibody pair without any significant modification. PMID- 26277395 TI - Human FAD synthase is a bi-functional enzyme with a FAD hydrolase activity in the molybdopterin binding domain. AB - FAD synthase (FMN:ATP adenylyl transferase, FMNAT or FADS, EC 2.7.7.2) is involved in the biochemical pathway for converting riboflavin into FAD. Human FADS exists in different isoforms. Two of these have been characterized and are localized in different subcellular compartments. hFADS2 containing 490 amino acids shows a two domain organization: the 3'-phosphoadenosine-5'-phosphosulfate (PAPS) reductase domain, that is the FAD-forming catalytic domain, and a resembling molybdopterin-binding (MPTb) domain. By a multialignment of hFADS2 with other MPTb containing proteins of various organisms from bacteria to plants, the critical residues for hydrolytic function were identified. A homology model of the MPTb domain of hFADS2 was built, using as template the solved structure of a T. acidophilum enzyme. The capacity of hFADS2 to catalyse FAD hydrolysis was revealed. The recombinant hFADS2 was able to hydrolyse added FAD in a Co(2+) and mersalyl dependent reaction. The recombinant PAPS reductase domain is not able to perform the same function. The mutant C440A catalyses the same hydrolytic function of WT with no essential requirement for mersalyl, thus indicating the involvement of C440 in the control of hydrolysis switch. The enzyme C440A is also able to catalyse hydrolysis of FAD bound to the PAPS reductase domain, which is quantitatively converted into FMN. PMID- 26277396 TI - Isoform-specific dynamic translocation of PKC by alpha1-adrenoceptor stimulation in live cells. AB - Protein kinase C (PKC) plays key roles in the regulation of signal transduction and cellular function in various cell types. At least ten PKC isoforms have been identified and intracellular localization and trafficking of these individual isoforms are important for regulation of enzyme activity and substrate specificity. PKC can be activated downstream of Gq-protein coupled receptor (GqPCR) signaling and translocate to various cellular compartments including plasma membrane (PM). Recent reports suggested that different types of GqPCRs would activate different PKC isoforms (classic, novel and atypical PKCs) with different trafficking patterns. However, the knowledge of isoform-specific activation of PKC by each GqPCR is limited. alpha1-Adrenoceptor (alpha1-AR) is one of the GqPCRs highly expressed in the cardiovascular system. In this study, we examined the isoform-specific dynamic translocation of PKC in living HEK293T cells by alpha1-AR stimulation (alpha1-ARS). Rat PKCalpha, betaI, betaII, delta, epsilon and zeta fused with GFP at C-term were co-transfected with human alpha1A AR into HEK293T cells. The isoform-specific dynamic translocation of PKC in living HEK293T cells by alpha1-ARS using phenylephrine was measured by confocal microscopy. Before stimulation, GFP-PKCs were localized at cytosolic region. alpha1-ARS strongly and rapidly translocated a classical PKC (cPKC), PKCalpha, (<30 s) to PM, with PKCalpha returning diffusively into the cytosol within 5 min. alpha1-ARS rapidly translocated other cPKCs, PKCbetaI and PKCbetaII, to the PM (<30 s), with sustained membrane localization. One novel PKC (nPKC), PKCepsilon, but not another nPKC, PKCdelta, was translocated by alpha1-AR stimulation to the PM (<30 s) and its membrane localization was also sustained. Finally, alpha1-AR stimulation did not cause a diacylglycerol-insensitive atypical PKC, PKCzeta translocation. Our data suggest that PKCalpha, beta and epsilon activation may underlie physiological and pathophysiological responses of alpha1-AR signaling for the phosphorylation of membrane-associated substrates including ion-channel and transporter proteins in the cardiovascular system. PMID- 26277397 TI - Keratin 8 is a novel autoantigen of rheumatoid arthritis. AB - OBJECTIVE: This research aims to verify Keratin 8 (K8) as a specific autoantigen in rheumatoid arthritis (RA). METHODS: First, total RNA was extracted from HaCaT cell to obtain cDNA by inverse transcription. Then, PCR was performed to amplify corresponding gene by K8 primers. Next, cloning, expression, and purification technology were used to obtain the recombinant human K8 (rhK8). At last, the purified rhK8, after identified by mass spectrometer, was used to perform further disease-related Western blotting and ELISA test with real clinical samples. RESULTS: Purified rhK8 was successfully obtained and then Western blotting confirmed antigenicity of K8 in rheumatoid arthritis. The reactivity of serum IgG against rhK8 was further detected in 34 of 50 RA patients (68%). The reactivity of RA serum IgG antibodies against K8 was significantly higher than healthy controls and systemic lupus erythematosus (SLE) patients. CONCLUSION: This research confirmed Keratin 8 as a novel autoantigen of RA. PMID- 26277398 TI - Metabolic, anabolic, and mitogenic insulin responses: A tissue-specific perspective for insulin receptor activators. AB - Insulin acts as the major regulator of the fasting-to-fed metabolic transition by altering substrate metabolism, promoting energy storage, and helping activate protein synthesis. In addition to its glucoregulatory and other metabolic properties, insulin can also act as a growth factor. The metabolic and mitogenic responses to insulin are regulated by divergent post-receptor signaling mechanisms downstream from the activated insulin receptor (IR). However, the anabolic and growth-promoting properties of insulin require tissue-specific inter relationships between the two pathways, and the nature and scope of insulin regulated processes vary greatly across tissues. Understanding the nuances of this interplay between metabolic and growth-regulating properties of insulin would have important implications for development of novel insulin and IR modulator therapies that stimulate insulin receptor activation in both pathway- and tissue-specific manners. This review will provide a unique perspective focusing on the roles of "metabolic" and "mitogenic" actions of insulin signaling in various tissues, and how these networks should be considered when evaluating selective pharmacologic approaches to prevent or treat metabolic disease. PMID- 26277399 TI - Maternal hyperthyroidism increases the susceptibility of rat adult offspring to cardiovascular disorders. AB - Suboptimal intrauterine conditions as changed hormone levels during critical periods of the development are considered an insult and implicate in physiological adaptations which may result in pathological outcomes in later life. This study evaluated the effect of maternal hyperthyroidism (hyper) on cardiac function in adult offspring and the possible involvement of cardiac Renin Angiotensin System (RAS) in this process. Wistar dams received orally thyroxin (12 mg/L) from gestational day 9 (GD9) until GD18. Adult offspring at postnatal day 90 (PND90) from hyper dams presented increased SBP evaluated by plethysmography and worse recovery after ischemia-reperfusion (I/R), as evidenced by decreased LVDP, +dP/dT and -dP/dT at 25 min of reperfusion and by increased infarct size. Increased cardiac Angiotensin I/II levels and AT1R in hyper offspring were verified. Herein, we provide evidences that maternal hyperthyroidism leads to altered expression of RAS components in adult offspring, which may be correlated with worse recovery of the cardiac performance after ischemic insults and hypertension. PMID- 26277400 TI - GnRH-(1-5) activates matrix metallopeptidase-9 to release epidermal growth factor and promote cellular invasion. AB - In the extracellular space, the gonadotropin-releasing hormone (GnRH) is metabolized by the zinc metalloendopeptidase EC3.4.24.15 (EP24.15) to form the pentapeptide, GnRH-(1-5). GnRH-(1-5) diverges in function and mechanism of action from GnRH in the brain and periphery. GnRH-(1-5) acts on the orphan G protein coupled receptor 101 (GPR101) to sequentially stimulate epidermal growth factor (EGF) release, phosphorylate the EGF receptor (EGFR), and facilitate cellular migration. These GnRH-(1-5) actions are dependent on matrix metallopeptidase (MMP) activity. Here, we demonstrated that these GnRH-(1-5) effects are dependent on increased MMP-9 enzymatic activity in the Ishikawa and ECC-1 cell lines. Furthermore, the effects of GnRH-(1-5) mediated by GPR101 and the subsequent increase in MMP-9 enzymatic activity lead to an increase in cellular invasion. These results suggest that GnRH-(1-5) and GPR101 regulation of MMP-9 may have physiological relevance in the metastatic potential of endometrial cancer cells. PMID- 26277402 TI - Activins and activin antagonists in the human ovary and ovarian cancer. AB - Activins are members of the transforming growth factor beta superfamily that play an important role in controlling cell proliferation and differentiation in many organs including the ovary. It is essential that activin signalling be tightly regulated as imbalances can lead to uncontrolled cell proliferation and cancer. This review describes the expression and function of the activins and their known antagonists in both normal and cancerous human ovaries. PMID- 26277401 TI - Bisphenol A (BPA) stimulates the interferon signaling and activates the inflammasome activity in myeloid cells. AB - Environmental factors contribute to the development of autoimmune diseases, including systemic lupus erythematosus (SLE), which exhibits a strong female bias (female-to-male ratio 9:1). However, the molecular mechanisms remain largely unknown. Because a feedforward loop between the female sex hormone estrogen (E2) and type I interferon (IFN-alpha/beta)-signaling induces the expression of certain p200-family proteins (such as murine p202 and human IFI16) that regulate innate immune responses and modify lupus susceptibility, we investigated whether treatment of myeloid cells with bisphenol A (BPA), an environmental estrogen, could regulate the p200-family proteins and activate innate immune responses. We found that treatment of murine bone marrow-derived cells (BMCs) and human peripheral blood mononuclear cells with BPA induced the expression of ERalpha and IFN-beta, activated the IFN-signaling, and stimulated the expression of the p202 and IFI16 proteins. Further, the treatment increased levels of the NLRP3 inflammasome and stimulated its activity. Accordingly, BPA-treatment of BMCs from non lupus-prone C57BL/6 and the lupus-prone (NZB*NZW)F1 mice activated the type I IFN-signaling, induced the expression of p202, and activated an inflammasome activity. Our study demonstrates that BPA-induced signaling in the murine and human myeloid cells stimulates the type I IFN-signaling that results in an induction of the p202 and IFI16 innate immune sensors for the cytosolic DNA and activates an inflammasome activity. These observations provide novel molecular insights into the role of environmental BPA exposures in potentiating the development of certain autoimmune diseases such as SLE. PMID- 26277403 TI - First Steps Towards Successful Post-Transplantation Therapy for Myeloid Malignancies after Allogeneic Blood Stem Cell Transplantation. PMID- 26277404 TI - School and peer influences on the academic outcomes of African American adolescents. AB - Little scholarship explores how adolescents' beliefs about school and peers influence the academic outcomes of African American boys and girls. The sample included 612 African American boys (N = 307, Mage = 16.84) and girls (N = 305, Mage = 16.79). Latent class analysis (LCA) revealed unique patterns for African American boys and girls. Findings indicate that for African American boys, school attachment was protective, despite having peers who endorsed negative achievement values. Furthermore, socio-economic (SES) status was associated with higher grade point averages (GPA) for African American girls. Overall, these findings underscore the unique role of school, peer, and gendered experiences in lives of African American adolescents. PMID- 26277405 TI - Disruptive behavior disorders and indicators of disinhibition in adolescents: The BRIEF-SR, anti-saccade task, and D-KEFS color-word interference test. AB - Disinhibition contributes to the development of disruptive behavior disorders (DBD) in adolescents. Self-reports and behavioral tasks are commonly used to assess disinhibition, each with their unique strengths and limitations. Accordingly, it is important to identify which measure, or combination thereof, is the most effective in predicting DBD symptoms. This study assessed the relationship between DBD (symptoms of ADHD/ODD/CD) and two behavioral disinhibition tasks: the anti-saccade task and the D-KEFS color-word interference test, as well as a self-report measure (the BRIEF-SR). The results indicated that the BRIEF-Inhibit scale accounted for the majority of the variance in the DBD sum score. The anti-saccade task and color-word interference test were also significantly associated with an increase in the number of DBD symptoms endorsed. These behavioral tasks accounted for 9% additional variance than the self-report alone. Therefore, combining self-report measures with behavioral disinhibition tasks may provide the most thorough assessment of adolescent DBD. PMID- 26277406 TI - Pandalisines A and B, novel indolizidine alkaloids from the leaves of Pandanus utilis. AB - Two novel alkaloids named pandalisines A (1) and B (2), constituting a new class of C8-substituted indolizidine moiety, were isolated from the leaves of Pandanus utilis. The structures of these new compounds were established by their mass and spectroscopic data. The absolute configuration was determined by the comparison of experimental CD and calculated ECD spectra. A plausible biosynthetic pathway for compounds 1 and 2 is advanced. The cytotoxic activities of the isolated alkaloids against A-549, Hep-G2, and MDA-MB-231 cancer cell lines were evaluated. The result showed that 1 and 2 are the first non-cytotoxic indolizidine alkaloids. PMID- 26277407 TI - Re-engineering nalidixic acid's chemical scaffold: A step towards the development of novel anti-tubercular and anti-bacterial leads for resistant pathogens. AB - Occurrence of antibacterial and antimycobacterial resistance stimulated a thrust to discover new drugs for infectious diseases. Herein we report the work on re engineering nalidixic acid's chemical scaffold for newer leads. Stepwise clubbing of quinoxaline, 1,2,4-triazole/1,3,4-oxadiazole with nalidixic acid yielded better compounds. Compounds were screened against ciprofloxacin resistant bacteria and Mycobacterium tuberculosis H37Rv species. Results were obtained as minimum inhibitory concentration, it was evident that molecule with quinoxaline linked azide as side chain served as antitubercular lead (<6.25 MUg/ml) whilst molecule with oxadiazole or triazole linked quinoxaline side chain served as anti bacterial lead. Few compounds were significantly active against Escherichia coli and Proteus vulgaris with MIC less than 0.06 MUg/ml and relatively potent than ciprofloxacin. No true compound was potentially active against Salmonella species as compared to amoxicillin. PMID- 26277408 TI - Effect of nutritive status on Mytilus galloprovincialis pollution biomarkers: Implications for large-scale monitoring programs. AB - Biomarkers have been extensively used in monitoring programs with the aim of assessing the biological effects of pollutants on marine organisms and determining environmental status. Data obtained from these programs are sometimes difficult to interpret due to the large amount of natural variables affecting biological processes, which could act as confounding factors on biomarker responses. The main aim of this work was to identify the effect of one of these variables, the food availability, and consequently, the mussel nutritive status, on biomarker responses. For that purpose, mussels (Mytilus galloprovincialis) were conditioned to three different food rations for 2 months in order to create three mussel nutritive statuses and afterwards, each status was exposed to three nominal concentrations of fluoranthene (FLU) for 3 weeks. A battery of biomarkers was considered in this study to cover a wide range of organism responses, both physiological (scope for growth - SFG) and biochemical (superoxide dismutase - SOD, catalase - CAT, glutathione reductase - GR, glutathione peroxidase - GPx, glutathione-S-transferase - GST and phenoloxidase - PO activities, and lipid membrane peroxidation - LPO). The results obtained, evidenced that most of the studied biomarkers (SFG, SOD, CAT, GPx, and PO) were strongly affected by mussel nutritive status, showing higher values at lower status, whereas the effect of toxicant was not always evident, masked by the nutritive status effect. This paper demonstrates that toxicants are not the only source of variability modulating pollution biomarkers, and confirms nutritive status as a major factor altering biochemical and physiological biomarkers. PMID- 26277410 TI - Parents' perspective on weight management interventions for adolescents with intellectual and developmental disabilities. AB - BACKGROUND: Adolescents with intellectual and developmental disabilities (IDD) have high rates of obesity. However, little research has been conducted demonstrating effective strategies and barriers for weight loss or weight management in adolescents with IDD. Furthermore, parents play a large role in terms of weight management in children and adolescents with IDD, and their views should be taken into consideration when designing a diet and PA intervention for weight management. OBJECTIVE: The aims of this study are to better understand the parents' perspectives on the strategies and barriers for helping children and adolescents with IDD be successful in a weight management program and to identify how this information to guide future approaches. METHODS: Semi-structured interviews were conducted in 18 parents whose children had just finished a diet and PA intervention. Interviews were transcribed verbatim, and thematic analysis was performed. RESULTS: Parents reported a positive attitude toward the program, liked the convenience of the program, and felt that they learned beneficial strategies to encourage healthy habits in the home. Parents found time to be a major barrier to supporting their child with a diet and PA intervention. Parents were willing to change their own dietary behaviors to help their children successfully follow a weight loss intervention; however, no parent reported changing their own PA levels. CONCLUSION: Future diet and PA studies should aim to reduce parental time commitment and increase importance of PA. PMID- 26277411 TI - Testing a structural model of young driver willingness to uptake Smartphone Driver Support Systems. AB - There is growing interest in the potential value of using phone applications that can monitor driver behaviour (Smartphone Driver Support Systems, 'SDSSs') in mitigating risky driving by young people. However, their value in this regard will only be realised if young people are willing to use this technology. This paper reports the findings of a study in which a novel structural model of willingness to use SDSSs was tested. Grounded in the driver monitoring and Technology Acceptance (TA) research literature, the model incorporates the perceived risks and gains associated with potential SDSS usage and additional social cognitive factors, including perceived usability and social influences. A total of 333 smartphone users, aged 18-24, with full Irish driving licenses completed an online questionnaire examining willingness or Behavioural Intention (BI) to uptake a SDSS. Following exploratory and confirmatory factor analyses, structural equation modelling indicated that perceived gains and social influence factors had significant direct effects on BI. Perceived risks and social influence also had significant indirect effects on BI, as mediated by perceived gains. Overall, this model accounted for 72.5% of the variance in willingness to uptake SDSSs. Multi-group structural models highlighted invariance of effects across gender, high and low risk drivers, and those likely or unlikely to adopt novel phone app technologies. These findings have implications for our understanding of the willingness of young drivers to adopt and use SDSSs, and highlight potential factors that could be targeted in behavioural change interventions seeking to improve usage rates. PMID- 26277409 TI - Inositol-phosphodihydroceramides in the periodontal pathogen Tannerella forsythia: Structural analysis and incorporation of exogenous myo-inositol. AB - BACKGROUND: Unique phosphodihydroceramides containing phosphoethanolamine and glycerol have been previously described in Porphyromonas gingivalis. Importantly, they were shown to possess pro-inflammatory properties. Other common human bacteria were screened for the presence of these lipids, and they were found, amongst others, in the oral pathogen Tannerella forsythia. To date, no detailed study into the lipids of this organism has been performed. METHODS: Lipids were extracted, separated and purified by HPTLC, and analyzed using GC-MS, ESI-MS and NMR. Of special interest was how T. forsythia acquires the metabolic precursors for the lipids studied here. This was assayed by radioactive and stable isotope incorporation using carbon-14 and deuterium labeled myo-inositol, added to the growth medium. RESULTS: T. forsythia synthesizes two phosphodihydroceramides (Tf GL1, Tf GL2) which are constituted by phospho-myo-inositol linked to either a 17 , 18-, or 19-carbon sphinganine, N-linked to either a branched 17:0(3-OH) or a linear 16:0(3-OH) fatty acid which, in Tf GL2, is, in turn, ester-substituted with a branched 15:0 fatty acid. T. forsythia lacks the enzymatic machinery required for myo-inositol synthesis but was found to internalize inositol from the medium for the synthesis of both Tf GL1 and Tf GL2. CONCLUSION: The study describes two novel glycolipids in T. forsythia which could be essential in this organism. Their synthesis could be reliant on an external source of myo-inositol. GENERAL SIGNIFICANCE: The effects of these unique lipids on the immune system and their role in bacterial virulence could be relevant in the search for new drug targets. PMID- 26277412 TI - Redox-implications associated with the formation of complexes between copper ions and reduced or oxidized glutathione. AB - Binding of copper by reduced glutathione (GSH) is generally seen as a mechanism to lower, if not abolish, the otherwise high electrophilicity and redox activity of its free ions. In recent years, however, this concept has been contradicted by new evidence revealing that, rather than stabilizing free copper ions, its binding to GSH leads to the formation of a Cu(I)-[GSH]2 complex capable of reducing molecular oxygen into superoxide. It is now understood that, under conditions leading to the removal of such radicals, the Cu(I)-[GSH]2 complex is readily oxidized into Cu(II)-GSSG. Interestingly, in the presence of a GSH excess, the latter complex is able to regenerate the superoxide-generating capacity of the complex it originated from, opening the possibility that a GSH dependent interplay exists between the reduced and the oxidized glutathione forms of these copper-complexes. Furthermore, recent evidence obtained from experiments conducted in non-cellular systems and intact mitochondria indicates that the Cu(II)-GSSG complex is also able to function in a catalytic manner as an efficient superoxide dismutating- and catalase-like molecule. Here we review and discuss the most relevant chemical and biological evidence on the formation of the Cu(I)-[GSH]2 and Cu(II)-GSSG complexes and on the potential redox implications associated with their intracellular occurrence. PMID- 26277413 TI - Metal complexes of 6-pyrazolylpurine derivatives as models for metal-mediated base pairs. AB - 6-(3,5-Dimethylpyrazol-1-yl)purine has recently been introduced as an artificial nucleobase for the specific recognition of canonical nucleobases via the formation of a metal-mediated base pair. We report here the synthesis and structural characterization by single crystal X-ray diffraction analysis of a series of metal complexes of the corresponding alkylated model nucleobases 9 methyl-6-(3,5-dimethylpyrazol-1-yl)purine 2 and 9-methyl-6-pyrazol-1-yl-purine 7. The sterically more demanding ligand 2 forms the Cu(2+) complexes [Cu(2)(NO3)2] and [Cu(2)Cl2] with a 1:1 stoichiometry of ligand and metal ion. In contrast, ligand 7 forms complexes [Cu(7)2(NO3)](NO3) and [Ag(7)2](ClO4) with a 2:1 stoichiometry. The molecular structures of [Cu(2)(NO3)2] and [Cu(2)Cl2] confirm the previously suggested coordination pattern, i.e. Cu(2+) is coordinated via the pyrazole nitrogen atom and the purine N7 position. The fact that different relative orientations of the two ligands in [Cu(7)2(NO3)](NO3) and [Ag(7)2](ClO4) are observed allows the prediction that the corresponding metal-mediated homo base pairs should be stable both in regular antiparallel-stranded and in the rare parallel-stranded double helices. PMID- 26277415 TI - Cytotoxicity of Ru(II) piano-stool complexes with chloroquine and chelating ligands against breast and lung tumor cells: Interactions with DNA and BSA. AB - The synthesis and spectroscopic characterization of nine pi-arene piano-stool ruthenium (II) complexes with aromatic dinitrogen chelating ligands or containing chloroquine (CQ), are described in this study: [Ru(eta(6)-C10H14)(phen)Cl]PF6 (1), [Ru(eta(6)-C10H14)(dphphen)Cl]PF6 (2), [Ru(eta(6)-C10H14)(bipy)Cl]PF6 (3), [Ru(eta(6)-C10H14)(dmebipy)Cl]PF6 (4) and [Ru(eta(6)-C10H14)(bdutbipy)Cl]PF6 (5), [Ru(eta(6)-C10H14)(phen)CQ](PF6)2 (6), [Ru(eta(6)-C10H14)(dphphen)CQ](PF6)2 (7), [Ru(eta(6)-C10H14)(bipy)CQ](PF6)2 (8), [Ru(eta(6)-C10H14)(dmebipy)CQ](PF6)2 (9): [1,10-phenanthroline (phen), 4,7-diphenyl-1,10-phenanthroline (dphphen), 2,2' bipyridine (bipy), 5,5'-dimethyl-2,2'-bipyridine (dmebipy), and 4,4'-di-t-butyl 2,2'-bipyridine (dbutbipy)]. The solid state structures of five ruthenium complexes (1-5) were determined by X-ray crystallography. Electrochemical experiments were performed by cyclic voltammetry to estimate the redox potential of the Ru(II)/Ru(III) couple in each case. Their interactions with DNA and BSA, and activity against four cell lines (L929, A549, MDA-MB-231 and MCF-7) were evaluated. Compounds 2, 6 through 9, interact with DNA which was comparable to the one observed for free chloroquine. The results of fluorescence titration revealed that these complexes strongly quenched the intrinsic fluorescence of BSA following a static quenching procedure. Binding constants (Kb) and the number of binding sites (n~1) were calculated using modified Stern-Volmer equations. The thermodynamic parameters DeltaG at different temperatures were calculated and subsequently the values of DeltaH and DeltaS were also calculated, which revealed that hydrophobic and electrostatic interactions play a major role in the BSA complex association. The MTT assay results indicated that complexes 2, 5 and 7 showed cytostatic effects at appreciably lower concentrations than those needed for cisplatin, chloroquine and doxorubicin. PMID- 26277414 TI - Insight into structural rearrangements and interdomain interactions related to electron transfer between flavin mononucleotide and heme in nitric oxide synthase: A molecular dynamics study. AB - Calmodulin (CaM) binding to nitric oxide synthase (NOS) enables a conformational change, in which the FMN domain shuttles between the FAD and heme domains to deliver electrons to the active site heme center. A clear understanding of this large conformational change is critical, since this step is the rate-limiting in NOS catalysis. Herein molecular dynamics simulations were conducted on a model of an oxygenase/FMN (oxyFMN) construct of human inducible NOS (iNOS). This is to investigate the structural rearrangements and the domain interactions related to the FMN-heme interdomain electron transfer (IET). We carried out simulations on the iNOS oxyFMN.CaM complex models in [Fe(III)][FMNH(-)] and [Fe(II)][FMNH] oxidation states, the pre- and post-IET states. The comparison of the dynamics and conformations of the iNOS construct at the two oxidation states has allowed us to identify key factors related to facilitating the FMN-heme IET process. The computational results demonstrated, for the first time, that the conformational change is redox-dependent. Predictions of the key interacting sites in optimal interdomain FMN/heme docking are well supported by experimental data in the literature. An intra-subunit pivot region is predicted to modulate the FMN domain motion and correlate with existence of a bottleneck in the conformational sampling that leads to the electron transfer-competent state. Interactions of the residues identified in this work are proposed to ensure that the FMN domain moves with appropriate degrees of freedom and docks to proper positions at the heme domain, resulting in efficient IET and nitric oxide production. PMID- 26277416 TI - Functional fluorescent nonporous silica nanoparticles as carriers for Pt(IV) anticancer prodrugs. AB - Multilayer fluorescent nonporous silica nanoparticles (SNPs) with an external shell containing primary amino groups were used as delivery systems for Pt(IV) candidate antitumor prodrugs. Spherical SNPs of three different sizes (diameter around 120, 100, and 50 nm) were loaded with two different complexes, namely (OC 6-33)-diamminebis(4-carboxybutanoato)dichloridoplatinum(IV) (1) and (OC-6-44) diammine(4-carboxybutanoato)dichloridoethanolatoplatinum(IV) (2), through the formation of amide bonds between the pendant amino groups on SNPs and the free carboxylic groups of the complexes. Complex 1 proved to cause heavy and irreversible agglomeration of SNPs; likely, the presence of two reactive carboxylic functionalities induces the formation of cross-links between the amino decorated SNPs. On the contrary, the conjugates 2-SNP, obtained from the monofunctionalized 2, afforded aqueous nano-suspensions reasonably stable toward aggregation. These solutions showed a limited Pt release in water in the absence of any reducing agents, mainly in form of a Pt(IV) derivative generated by the hydrolysis of the Si-O-Si bond of the functionalized arms attached to silica. In the presence of ascorbic acid, the reduction Pt(IV) -> Pt(II) caused the release of the active metabolite cisplatin. Conjugates 2-SNP exhibited much better antiproliferative activity on the Pt-sensitive ovarian A2780 cell line than parent cisplatin and free 2, due to their more efficient cellular uptake. PMID- 26277417 TI - NO2(-)-mediated nitrosylation of ferrous microperoxidase-11. AB - Microperoxidase-11 (MP11) is an undecapeptide derived from horse heart cytochrome c (cyt c) and characterized by a covalently-linked solvent-exposed heme group. Here, kinetics of the NO2(-)-mediated nitrosylation of ferrous MP11 (MP11-Fe(II)) is reported. Data were obtained between pH6.4 and 8.2, at 20.0 degrees C. The NO2(-)-mediated conversion of MP11-Fe(II) to MP11-Fe(II)-NO requires one proton; accordingly, values of the apparent second-order rate constant (kon) decrease by about two orders of magnitude from (2.9+/-0.3)*10(1)M(-1)s(-1) to (5.0+/-0.6)*10( 1)M(-1)s(-1) upon increasing pH from 6.4 to pH8.2. The slope of the linear fitting of Logkon versus pH is -1.00+/-0.06. Values of kon for the NO2(-) mediated nitrosylation of MP11-Fe(II) are similar to those of penta-coordinated cardiolipin-bound horse heart cyt c, exceeding by about two orders of magnitude those of wild-type horse heart cyt c. Present results highlight the role of heme distal residues in modulating horse heart cyt c reactivity. PMID- 26277418 TI - GoFDR: A sequence alignment based method for predicting protein functions. AB - In this study, we developed a method named GoFDR for predicting Gene Ontology (GO)-based protein functions. The input for GoFDR is simply a query sequence based multiple sequence alignment (MSA) produced by PSI-BLAST. For each GO term annotated to the sequences in the MSA, GoFDR identifies a number of functionally discriminating residues (FDRs) specific to the GO term, and scores the query sequence using a position specific scoring matrix (PSSM) constructed for the FDRs. The raw score is then converted into a probability score according to a score-to-probability table prepared from training sequences. GoFDR outperformed three sequence-based methods for predicting GO functions in a benchmark of 18,520 sequences. In addition, GoFDR was ranked one of the top methods according to the preliminary evaluation report released by the 2nd Critical Assessment of Function Annotation (CAFA2) project. Finally, we applied GoFDR to the complete human proteome sequences, and showed that the predictions made by GoFDR with high confidence significantly expanded current annotations of human proteome. As such, GoFDR is of great value not only for annotating protein functions in newly sequenced genomes, but also for characterizing the function of proteins of interest. PMID- 26277419 TI - A modified bilateral carotid artery stenosis procedure to develop a chronic cerebral hypoperfusion rat model with an increased survival rate. AB - BACKGROUND: Bilateral carotid artery occlusion (2-vessel occlusion, 2VO) in rats is a classic and frequently used approach to develop an animal model of chronic cerebral hypoperfusion. However, this method results in substantial mortality in rats. NEW METHOD: We investigated whether a modified 2VO procedure, which induces bilateral carotid artery stenosis via ligation of each bilateral common carotid artery (CCA) with a 32 gauge (G) needle followed by needle removal, could produce a chronic cerebral hypoperfusion rat model with an increased survival rate. Sprague-Dawley (SD) rats were treated with the standard or modified 2VO procedure, and changes in cerebral blood flow (CBF) and survival rates were determined. On day 28, cognitive function was assessed with the Morris Water Maze (MWM) test, and neuronal survival and degeneration within the hippocampal CA1 area were measured. Damage to the white matter (WM) within the corpus striatum was assessed via Luxol fast blue (LFB) staining and analyses analyzing the levels of the myelin basic protein (MBP) protein levels. RESULTS: The modified 2VO procedure induced similar cognitive impairments, hippocampal lesions and WM damage compared with the standard 2VO procedure in rats; however, it had an increased survival rate. Comparison with existing methods This novel method can be used to quickly and effectively establish a chronic cerebral hypoperfusion rat model with common materials and an improved survival rate. CONCLUSION: Bilateral carotid artery stenosis using a 32 G needle is a useful and reliable method to develop a rat model of chronic cerebral hypoperfusion with increased survival. PMID- 26277420 TI - Design of a fused phantom for quantitative evaluation of brain metabolites and enhanced quality assurance testing for magnetic resonance imaging and spectroscopy. AB - BACKGROUND: Magnetic resonance imaging and spectroscopy (MRI-MRS) is a useful tool for the identification and evaluation of chemical changes in anatomical regions. Quality assurance (QA) is performed in either images or spectra using QA phantom. Therefore, consistent and uniform technical MRI-MRS QA is crucial. NEW METHOD: Here we developed an MRI-MRS fused phantom along with the inserts for metabolite quantification to simultaneously optimize QA parameters for both MRI and MRS. T1- and T2-weighted images were obtained and MRS was performed with point-resolved spectroscopy. RESULTS: Using the fused phantom, the results of measuring MRI factors were: geometric distortion, <2% and +/- 2 mm; image intensity uniformity, 83.09 +/- 1.33%; percent-signal ghosting, 0.025 +/- 0.004; low-contrast object detectability, 27.85 +/- 0.80. In addition, the signal-to noise ratio of N-acetyl-aspartate was consistently high (42.00 +/- 5.66). COMPARISON WITH EXISTING METHODS: In previous studies, MR phantoms could not obtain information from both images and spectra in the MR scanner simultaneously. Here we designed and developed a phantom for accurate and consistent QA within the acceptance range. It is important to take into account variations in the QA value using the MRI-MRS phantom, when comparing to other clinical or research MR scanners. CONCLUSIONS: The MRI-MRS QA factors obtained simultaneously using the phantom can facilitate evaluation of both images and spectra, and provide guidelines for obtaining MRI and MRS QA factors simultaneously. PMID- 26277421 TI - Optimizing spatial patterns with sparse filter bands for motor-imagery based brain-computer interface. AB - BACKGROUND: Common spatial pattern (CSP) has been most popularly applied to motor imagery (MI) feature extraction for classification in brain-computer interface (BCI) application. Successful application of CSP depends on the filter band selection to a large degree. However, the most proper band is typically subject specific and can hardly be determined manually. NEW METHOD: This study proposes a sparse filter band common spatial pattern (SFBCSP) for optimizing the spatial patterns. SFBCSP estimates CSP features on multiple signals that are filtered from raw EEG data at a set of overlapping bands. The filter bands that result in significant CSP features are then selected in a supervised way by exploiting sparse regression. A support vector machine (SVM) is implemented on the selected features for MI classification. RESULTS: Two public EEG datasets (BCI Competition III dataset IVa and BCI Competition IV IIb) are used to validate the proposed SFBCSP method. Experimental results demonstrate that SFBCSP help improve the classification performance of MI. COMPARISON WITH EXISTING METHODS: The optimized spatial patterns by SFBCSP give overall better MI classification accuracy in comparison with several competing methods. CONCLUSIONS: The proposed SFBCSP is a potential method for improving the performance of MI-based BCI. PMID- 26277422 TI - [Protocols]. PMID- 26277423 TI - Five-Year Recovery: A New Standard for Assessing Effectiveness of Substance Use Disorder Treatment. PMID- 26277424 TI - SW1PerS: Sliding windows and 1-persistence scoring; discovering periodicity in gene expression time series data. AB - BACKGROUND: Identifying periodically expressed genes across different processes (e.g. the cell and metabolic cycles, circadian rhythms, etc) is a central problem in computational biology. Biological time series may contain (multiple) unknown signal shapes of systemic relevance, imperfections like noise, damping, and trending, or limited sampling density. While there exist methods for detecting periodicity, their design biases (e.g. toward a specific signal shape) can limit their applicability in one or more of these situations. METHODS: We present in this paper a novel method, SW1PerS, for quantifying periodicity in time series in a shape-agnostic manner and with resistance to damping. The measurement is performed directly, without presupposing a particular pattern, by evaluating the circularity of a high-dimensional representation of the signal. SW1PerS is compared to other algorithms using synthetic data and performance is quantified under varying noise models, noise levels, sampling densities, and signal shapes. Results on biological data are also analyzed and compared. RESULTS: On the task of periodic/not-periodic classification, using synthetic data, SW1PerS outperforms all other algorithms in the low-noise regime. SW1PerS is shown to be the most shape-agnostic of the evaluated methods, and the only one to consistently classify damped signals as highly periodic. On biological data, and for several experiments, the lists of top 10% genes ranked with SW1PerS recover up to 67% of those generated with other popular algorithms. Moreover, the list of genes from data on the Yeast metabolic cycle which are highly-ranked only by SW1PerS, contains evidently non-cosine patterns (e.g. ECM33, CDC9, SAM1,2 and MSH6) with highly periodic expression profiles. In data from the Yeast cell cycle SW1PerS identifies genes not preferred by other algorithms, hence not previously reported as periodic, but found in other experiments such as the universal growth rate response of Slavov. These genes are BOP3, CDC10, YIL108W, YER034W, MLP1, PAC2 and RTT101. CONCLUSIONS: In biological systems with low noise, i.e. where periodic signals with interesting shapes are more likely to occur, SW1PerS can be used as a powerful tool in exploratory analyses. Indeed, by having an initial set of periodic genes with a rich variety of signal types, pattern/shape information can be included in the study of systems and the generation of hypotheses regarding the structure of gene regulatory networks. PMID- 26277425 TI - Surgery resident participation in short-term humanitarian international surgical missions can supplement exposure where program case volumes are low. AB - BACKGROUND: General surgery training programs face declining case volume and diversity. We wanted to determine if resident participation in international surgical missions would increase exposure to cases underrepresented in our program case mix. METHODS: Accreditation Council for Graduate Medical Education program data from 2008 to 2011 (University of Medicine and Dentistry-New Jersey Medical School, Newark, NJ) were analyzed to identify categories where volume was below national average. This was compared with case logs from 3 missions conducted by International Surgical Health Initiatives between 2011 and 2012. RESULTS: All chief residents completed more than minimum required index cases. Categories head and neck, alimentary tract, abdomen, and endocrine showed percentile below national average. Seven residents participated in 3 missions to Philippines and Sierra Leone. Sixty-five percent of the operations performed were in the 4 low-volume categories. CONCLUSIONS: International surgery missions expose residents to a high volume and variety of cases. Participation can be one way to increase case volume and diversity during training. Cases completed on missions with board certified surgeons should be considered for Accreditation Council for Graduate Medical Education credit. PMID- 26277427 TI - Not just ticking all the boxes. Problem based learning and mental health nursing. A review. AB - BACKGROUND: The practice and policy of mental health nursing are changing. Integration of health and social care, an increased emphasis on wellness and recovery and greater expectation of involvement from both service users and carers require competence in both group and interpersonal working. The active and dynamic processes of problem based learning provide the ideal environment to achieve proficiency in these skills. OBJECTIVES: The aim of this review was to understand those programme elements that best support the delivery of a problem based learning module. DATA SOURCES: This study utilised a standard module evaluation. REVIEW METHODS: A systematic analysis of completed module evaluations allowed key themes to be established. RESULTS: Problem based learning helps develop the skills and attributes that mental health nursing need in an increasing collaborative and wellness focused practice environment. Successful integration of PBL is more likely to occur when student centred approaches are already incorporated within a programme. Creating the right conditions for learning are key to successful facilitation of PBL groups. CONCLUSIONS: Successful implementation of PBL requires identification of relevance to practice by students, a programme approach that is compatible with the aims and philosophy of PBL and a form of facilitation that encourages development of student autonomy. PMID- 26277426 TI - The gap between training and practice of prescribing of drugs by nurses in the primary health care: a case study in Brazil. AB - BACKGROUND: In many countries, the inclusion of nurses as prescribers is considered to be an advanced practice. In Brazil, such prescriptions are legally regulated and restricted to primary health care protocols. The presence of prescribing nurses has provoked a debate among medical and nursing corporations. However, there are few studies examining the qualifications, protocols and in service training that are aimed at prescribing nurses in primary health care. OBJECTIVE: We sought to investigate possible gaps between the education, qualifications, self-assessments and practice of prescribing medicine in primary health care from the perspective of nurses. DESIGN: This investigation is a case study with a qualitative approach. SETTING: This research was conducted in a Brazilian municipality with 84.04% family health strategy coverage and 400,002 inhabitants in northeast Brazil. PARTICIPANTS: The participants were an intentional sample of 37 nurses in primary health care who were linked to the family health strategy. METHODS: The study was conducted between August and November 2011 with four focus groups, a script validated by the Delphi technique, and a pilot study. This study addressed the qualifications for the prescription of medication, the sufficiency of the Ministry of Health protocols and self assessments of the ability to prescribe. Qualitative analysis was applied. RESULTS: All nurses reported having received insufficient training in the discipline of pharmacology to qualify them for prescriptive practice. The nurses emphasised the need for post-graduate training, the importance of clinical experience, and the lack of discussions and training. Only a small number of nurses self-assessed themselves as competent in prescribing drugs, and the others revealed fears of causing adverse reactions to medication. CONCLUSIONS: There are gaps in the education, training, and daily demands of the prescription of medication by nurses in primary health care. It is suggested that prescription practices should be incorporated into undergraduate studies and continuing education in health services. PMID- 26277428 TI - Qualifications for nurses for the care of patients with dementia and support to their caregivers: A pilot evaluation of the dementia care management curriculum. AB - BACKGROUND: A substantial increase of people with dementia (PwD) is predicted for the future. Nurses are taking over important tasks to support PwD, which requires a specialized qualification. OBJECTIVES: The aim was to identify points for revision and to further improve the Dementia Care Manager (DCM) curriculum as a basis for probable qualification of nurses caring for PwD. DESIGN: We conducted a summative evaluation study to revise the first version of the DCM curriculum. SETTING: The study was conducted in the primary health care setting. PARTICIPANTS: Nurses and lecturers of the first theoretical and practical implementation were involved. METHODS: Questionnaire-based interviews with nurses and lecturers after every module during the theoretical qualification. Besides, nurses rated the curriculum after the end of the theoretical part and evaluated the DCM tasks and the usefulness of the curriculum contents after the practical phase in questionnaire-based interviews. Descriptive statistics were used for analysis. RESULTS: A total of five nurses and 33 lecturers participated in the first theoretical and practical implementation of the DCM qualification. Generally, nurses and lecturers assessed the curriculum contents as "very important" or "important." In particular, the job-related issues, the variety of course topics and the close combination of theory and practice were highly valued. The practical implementation of the DCM was rated predominantly as "important" by nurses for the delivery of care for PwD. To optimize the theoretical DCM curriculum, participants suggested increasing the number of lessons for two of the modules (gerontopsychiatry, interdisciplinary case reviews). Furthermore, nurses preferred a longer practical phase, whereas some lecturers called for larger group sizes of participants. CONCLUSIONS: The DCM qualification enhances nurses' competencies to care for PwD. The curriculum regards an interprofessional, cooperative team approach as the potential to improve health care supply for demented people and to better support their caregivers. PMID- 26277430 TI - Application of 1H NMR spectroscopy-based metabonomics to feces of cervical cancer patients with radiation-induced acute intestinal symptoms. AB - OBJECTIVE: Radiation-induced acute intestinal symptoms (RIAISs) are a common complication of radiotherapy for cervical cancer. The aim of this study was to use (1)H nuclear magnetic resonance ((1)H NMR) combined with chemometric analysis to develop a metabolic profile of patients with RIAISs. METHODS: Fecal samples were collected from 66 patients with cervical cancer before and after pelvic radiotherapy. After radiotherapy, RIAISs occurred in eleven patients. We selected another 11 patients from participants without RIAISs whose age, stage, histological type and treatment methods are matched with RIAIS patients as the control group. (1)H NMR spectroscopy combined with multivariate pattern recognition analysis was used to generate metabolic profile data, as well as to establish a RIAIS-specific metabolic phenotype. RESULTS: Orthogonal partial least squares discriminant analysis was used to distinguish samples between the pre- and post-radiotherapy RIAIS patients and between RIAIS patients and controls. Fecal samples from RIAIS patients after pelvic radiotherapy were characterized by increased concentrations of alpha-ketobutyrate, valine, uracil, tyrosine, trimethylamine N-oxide, phenylalanine, lysine, isoleucine, glutamine, creatinine, creatine, bile acids, aminohippurate, and alanine, accompanied by reduced concentrations of alpha-glucose, n-butyrate, methylamine, and ethanol relative to samples from RIAIS patients before pelvic radiotherapy, while in RIAIS patients relative to controls, trimethylamine, n-butyrate, fumarate and acetate were down regulated and valine, TMAO, taurine, phenylalanine, lactate, isoleucine and creatinine were up-regulated. CONCLUSIONS: We obtained the metabolic profile of RIAIS patients from fecal samples using NMR-based metabonomics. This profile has the potential to be developed into a novel clinical tool for RIAIS diagnosis or therapeutic monitoring, and could contribute to an improved understanding of the disease mechanism. However, because of the limitations of methods, technique, bacterial contamination of feces and small sample size, further research and verification are needed. PMID- 26277429 TI - Does laboratory cue reactivity correlate with real-world craving and smoking responses to cues? AB - BACKGROUND: Laboratory cue reactivity (CR) assessments are used to assess smokers' responses to cues. Likewise, EMA recording is used to characterize real world response to cues. Understanding the relationship between CR and EMA responses addresses the ecological validity of CR. METHODS: In 190 daily smokers not currently quitting, craving and smoking responses to cues were assessed in laboratory CR and by real-world EMA recording. Separate CR sessions involved 5 smoking-relevant cues (smoking, alcohol, negative affect, positive affect, smoking prohibitions), and a neutral cue. Subjects used EMA to monitor smoking situations for 3 weeks, completing parallel situational assessments (presence of others smoking, alcohol consumption, negative affect, positive affect, and smoking prohibitions, plus current craving) in smoking and non-smoking occasions (averaging 70 and 60 occasions each). Analyses correlated CR craving and smoking cue responses with EMA craving and smoking correlations with similar cues. RESULTS: Although some cues did not show main effects on average craving or smoking, a wide range of individual differences in response to cues was apparent in both CR and EMA data, providing the necessary context to assess their relationship. Laboratory CR measures of cue response were not correlated with real-world cue responses assessed by EMA. The average correlation was 0.03; none exceeded 0.32. One of 40 correlations examined was significantly greater than 0. CONCLUSIONS: Laboratory CR measures do not correlate with EMA-assessed craving or smoking in response to cues, suggesting that CR measures are not accurate predictors of how smokers react to relevant stimuli in the real world. PMID- 26277431 TI - Coronary stenosis risk analysis following Hodgkin lymphoma radiotherapy: A study based on patient specific artery segments dose calculation. AB - BACKGROUND AND PURPOSE: The dose effect-effect relationship for cardiac diseases following radiotherapy suffers from uncertainties. Three dimensional coronary artery (CA) dose calculation after mediastinal Hodgkin lymphoma radiotherapy was performed, using the patient's coronary CT angiography (CCTA), and the relationship between the coronary arteries' radiation doses and the risk of stenosis was estimated. MATERIALS AND METHODS: Radiotherapy simulation CT scans and CCTAs of patients treated for a mediastinal Hodgkin lymphoma were used to merge thoracic and detailed cardiovascular anatomies. Radiation treatment parameters were used to estimate CA radiation doses. Twenty-one patients without coronary stenosis (controls) were matched with twelve patients with stenosis (cases). CA segments were considered as sub-volumes of interest. Radiation doses to stenotic segments were compared with those received by normal segments (from cases and controls) using a logistic regression. RESULTS: In eleven cases out of twelve, the highest of the coronary dose distribution was on a damaged segment. Logistic regression with CA segments yielded an odds ratio associated with the risk of coronary stenosis of 1.049 per additional gray with the CA segment median dose (95% confidence interval, 1.004-1.095; p-value <0.05). CONCLUSION: The CA segment dose significantly increased the risk of stenosis on the segment. Such personalized CA dose calculations on larger cohorts are expected to improve the understanding of the cardiovascular radiation dose-effect relationship. PMID- 26277432 TI - In vivo studies of the PARP inhibitor, AZD-2281, in combination with fractionated radiotherapy: An exploration of the therapeutic ratio. AB - BACKGROUND AND PURPOSE: Pre-clinical data have shown that PARP inhibitors (PARPi) may increase the efficacy of radiotherapy in prostate cancer. However, it is uncertain as to whether PARPi lead to clonogenic kill when combined with radiotherapy (RT). MATERIAL AND METHODS: We tested the PARP inhibitor AZD-2281 as a radiosensitizing agent under oxic and hypoxic conditions for clonogenic survival in vitro and in vivo using the human prostate cancer cell line, 22Rv1. In addition, the effects of PARPi+RT on normal tissue were investigated using a crypt clonogenic assay. RESULTS: AZD-2281 inhibited cellular PARP activity under both oxic and hypoxic conditions. The addition of AZD-2281 radiosensitized 22Rv1 cells under oxia, acute hypoxia and chronic hypoxia in vitro. The combination of AZD-2281 with fractionated radiotherapy resulted in a significant growth delay and clonogenic kill in vivo. No increased gut toxicity was observed using this combined PARPi+radiotherapy regimen. CONCLUSIONS: This is the first preclinical study to demonstrate direct clonogenic kill in vivo by the addition of AZD-2281 to radiotherapy. As we did not observe gut toxicity, the use of PARPi in the context of prostate cancer radiotherapy warrants further investigation in clinical trials. PMID- 26277434 TI - A MLC-based inversely optimized 3D spatially fractionated grid radiotherapy technique. AB - This study presents a MLC-based, 3D grid-therapy technique with characteristics of both 3D-conformal-radiotherapy and grid-therapy. It generates a brachytherapy like dose distribution, with D50% of 20, 9.8, 5.4 and 2.9-Gy, for the spheres, target, 1 cm-outershell and 2 cm-outershell, respectively. It may provide a strategy to deliver ablative doses to large tumors safely. PMID- 26277433 TI - Evaluation of a 36 Gy elective node irradiation dose in anal cancer. AB - PURPOSE: To retrospectively analyze the efficacy of 36 Gy of elective node irradiation and report patterns of recurrence in patients with anal cancer treated by chemoradiation with the same radiotherapy (RT) treatment scheme. METHODS AND MATERIALS: Between January 1996 and December 2013, 142 patients with anal squamous cell cancer were scheduled to receive a dose of 36 Gy of elective node irradiation (ENI) to the inguinal area and whole pelvis over 4 weeks followed after a 2-week gap by a boost dose of 23.4 Gy over 17 days to the macroscopic disease. Mitomycin C combined with fluorouracil, capecitabin or cisplatin was given at day 1 of each sequence of RT. RESULTS: Disease stages were I: 3, II: 78, IIIA: 23, IIIB: 38. Compliance rates were 97.2% with RT and 87.9% with chemotherapy. After a median follow up of 48 months [3.6-192], estimated 5 year overall survival and colostomy-free survival were 75.4% and 85.3% respectively. Eleven patients (7.7%) never achieved a complete response, 15 had a local component of recurrence and 5 a regional one. One patient had failure in the common iliac node area outside the treatment fields. The inguinal control rate was 98.5%. The 5-year tumor and nodal control rates were 81.5% and 96.0%, respectively. CONCLUSION: Chemoradiation with a dose of 36 Gy ENI achieved excellent nodal control. However, it is necessary to improve the 5-year control rate of the primary tumor. Omitting the gap and using additional doses per fraction or hyper-fractionation are to be explored. PMID- 26277435 TI - Modeling the risk of radiation-induced lung fibrosis: Irradiated heart tissue is as important as irradiated lung. AB - PURPOSE: We used normal tissue complication probability (NTCP) modeling to explore the impact of heart irradiation on radiation-induced lung fibrosis (RILF). MATERIALS AND METHODS: We retrospectively reviewed for RILF 148 consecutive Hodgkin lymphoma (HL) patients treated with sequential chemo radiotherapy (CHT-RT). Left, right, total lung and heart dose-volume and dose mass parameters along with clinical, disease and treatment-related characteristics were analyzed. NTCP modeling by multivariate logistic regression analysis using bootstrapping was performed. Models were evaluated by Spearman Rs coefficient and ROC area. RESULTS: At a median time of 13months, 18 out of 115 analyzable patients (15.6%) developed RILF after treatment. A three-variable predictive model resulted to be optimal for RILF. The two models most frequently selected by bootstrap included increasing age and mass of heart receiving >30Gy as common predictors, in combination with left lung V5 (Rs=0.35, AUC=0.78), or alternatively, the lungs near maximum dose D2% (Rs=0.38, AUC=0.80). CONCLUSION: CHT-RT may cause lung injury in a small, but significant fraction of HL patients. Our results suggest that aging along with both heart and lung irradiation plays a fundamental role in the risk of developing RILF. PMID- 26277437 TI - Managing Anterior Shoulder Dislocation. PMID- 26277438 TI - A Highly Mobile Mass in the Anterior Left Ventricular Outflow Tract Immediately Beneath a Heavily Calcified, Stenotic Aortic Valve: Vegetation, Thrombus, or Neoplasm? PMID- 26277439 TI - An Accidental Career in Geriatrics. PMID- 26277436 TI - Brain-peripheral cell crosstalk in white matter damage and repair. AB - White matter damage is an important part of cerebrovascular disease and may be a significant contributing factor in vascular mechanisms of cognitive dysfunction and dementia. It is well accepted that white matter homeostasis involves multifactorial interactions between all cells in the axon-glia-vascular unit. But more recently, it has been proposed that beyond cell-cell signaling within the brain per se, dynamic crosstalk between brain and systemic responses such as circulating immune cells and stem/progenitor cells may also be important. In this review, we explore the hypothesis that peripheral cells contribute to damage and repair after white matter damage. Depending on timing, phenotype and context, monocyte/macrophage can possess both detrimental and beneficial effects on oligodendrogenesis and white matter remodeling. Endothelial progenitor cells (EPCs) can be activated after CNS injury and the response may also influence white matter repair process. These emerging findings support the hypothesis that peripheral-derived cells can be both detrimental or beneficial in white matter pathology in cerebrovascular disease. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID- 26277440 TI - EPHECT III: Health risk assessment of exposure to household consumer products. AB - In the framework of the EU EPHECT project (Emissions, Exposure Patterns and Health Effects of Consumer Products in the EU), irritative and respiratory effects were assessed in relation to acute (30-min) and long-term (24-h) inhalation exposure to key and emerging indoor air pollutants emitted during household use of selected consumer products. A detailed Health Risk Assessment (HRA) was performed for five selected pollutants of respiratory health relevance, namely acrolein, formaldehyde, naphthalene, d-limonene and alpha-pinene. For each pollutant, the Critical Exposure Limit (CEL) was compared to indoor air concentrations and exposure estimates for the use of 15 selected consumer products by two population groups (housekeepers and retired people) in the four geographical regions of Europe (North, West, South, East), which were derived previously based on microenvironmental modelling. For the present HRA, health based CELs were derived for certain compounds in case indoor air quality guidelines were not available by the World Health Organization for end-points relevant to the current study. For each pollutant, the highest indoor air concentrations in each microenvironment and exposure estimates across home microenvironments during the day were lower than the corresponding acute and long term CELs. However, considerable contributions, especially to acute exposures, were obtained in some cases, such as formaldehyde emissions resulting from single product use of a floor cleaning agent (82% CEL), a candle (10% CEL) and an electric air freshener (17% CEL). Regarding multiple product use, the case of 30 min formaldehyde exposure reaching 34% CEL when eight product classes were used across home microenvironments, i.e. all-purpose/kitchen/floor cleaning agents, furniture/floor polish, combustible/electric air fresheners, and perfume, needs to be highlighted. Such estimated values should be evaluated with caution, as these may be attributed to the exposure scenarios specifically constructed for the present study, following a 'most-representative worst-case scenario' approach for exposure and health risk assessment. PMID- 26277441 TI - Development of an integrated methodology for the sustainable environmental and socio-economic management of river ecosystems. AB - The development of the Water Framework Directive aimed to establish an integrated framework of water management at European level. This framework revolves around inland surface waters, transitional waters, coastal waters and ground waters. In the process of achieving the environment and ecological objectives set from the Directive, the role of economics is put in the core of the water management. An important feature of the Directive is the recovery of total economic cost of water services by all users. The total cost of water services can be disaggregated into environmental, financial and resource costs. Another important aspect of the directive is the identification of major drivers and pressures in each River Basin District. We describe a methodology that is aiming to achieve sustainable and environmental and socioeconomic management of freshwater ecosystem services. The Ecosystem Services Approach is in the core of the suggested methodology for the implementation of a more sustainable and efficient water management. This approach consists of the following three steps: (i) socio economic characterization of the River Basin area, (ii) assessment of the current recovery of water use cost, and (iii) identification and suggestion of appropriate programs of measures for sustainable water management over space and time. This methodology is consistent with a) the economic principles adopted explicitly by the Water Framework Directive (WFD), b) the three-step WFD implementation approach adopted in the WATECO document, c) the Ecosystem Services Approach to valuing freshwater goods and services to humans. Furthermore, we analyze how the effects of multiple stressors and socio-economic development can be quantified in the context of freshwater resources management. We also attempt to estimate the value of four ecosystem services using the benefit transfer approach for the Anglian River Basin, which showed the significance of such services. PMID- 26277442 TI - Adaptation strategies for water supply management in a drought prone Mediterranean river basin: Application of outranking method. AB - The regional water allocation planning is one of those complex decision problems where holistic approach to water supply management considering different criteria would be valuable. However, multi-criteria decision making with diverse indicators measured on different scales and uncertainty levels is difficult to solve. Objective of this paper is to develop scenarios for the future imbalances in water supply and demand for a water stressed Mediterranean area of Northern Spain (Tarragona) and to test the applicability and suitability of an outranking method ELECTRE-III-H for evaluating sectoral water allocation policies. This study is focused on the use of alternative water supply scenarios to fulfil the demand of water from three major sectors: domestic, industrial and agricultural. A detail scenario planning for regional water demand and supply has been discussed. For each future scenario of climate change, the goal is to obtain a ranking of a set of possible actions with regards to different types of indicators (costs, water stress and environmental impact). The analytical method used is based on outranking models for decision aid with hierarchical structures of criteria and ranking alternatives using partial preorders based on pairwise preference relations. We compare several adaptation measures including alternative water sources (reclaimed water and desalination); inter basin water transfer and sectoral demand management coming from industry, agriculture and domestic sectors and tested the sustainability of management actions for different climate change scenarios. Results have shown use of alternative water resources as the most reliable alternative with medium reclaimed water reuse in industry and agriculture and low to medium use of desalination water in domestic and industrial sectors as the best alternative. The proposed method has several advantages such as the management of heterogeneous scales of measurement without requiring any artificial transformation and the management of uncertainty by means of comparisons at a qualitative level in terms of the decision maker preferences. PMID- 26277443 TI - Quantitation of eleven active compounds of Aidi injection in rat plasma and its application to comparative pharmacokinetic study. AB - Aidi injection has been widely used for the treatment of colorectal cancer. The purpose of this study was to develop a sensitive and reliable method for simultaneous quantitation of 11 main active ingredients in Aidi injection and to compare the pharmacokinetics of these ingredients in normal and colorectal model cancer rats after tail vein injection. After being extracted by isopropanol-ethyl acetate (1:1, v/v), the plasma samples were analyzed with domperidone as internal standard. Then the analytes were separated on a Venusil MP C18 column with 0.15% formic acid and methanol. The detection was performed on HPLC-MS/MS system with turbo ion spray source in the positive ion and multiple reaction-monitoring mode. The assay was shown to be linear over the range of 0.004-4.0MUgmL(-1) of syringin B, astragaloside II and isofraxidin; 0.01-10.0MUgmL(-1) of calycosin-7-O-beta-d glucoside and astragaloside IV; 0.02-20.0MUgmL(-1) of ginsenoside Rg1, Rb1, Rc and Rd; 0.04-40.0MUgmL(-1) of syringin E; 0.06-60.0MUgmL(-1) of ginsenoside Re. And the validated method has been successfully applied to compare pharmacokinetic profiles of the 11 ingredients in plasma. The pharmacokinetic results showed here were significant differences in pharmacokinetic parameters for eight analytes between two groups after injection, while no significant differences for astragaloside II, astragaloside IV and ginsenoside Rc. The present study has the advantages of short analysis time and easy sample preparation, which could more comprehensively reflect the quality of Aidi injection in single run. The method proposed could be of great use for pharmacokinetics, bioavailability or bioequivalence studies of Aidi injection in biological samples. PMID- 26277444 TI - Diagnostic performance of the Selvester QRS scoring system in relation to clinical ECG assessment of patients with lateral myocardial infarction using cardiac magnetic resonance as reference standard. AB - BACKGROUND: The Selvester QRS scoring system has previously been shown to enable estimation of myocardial infarct (MI) size by quantitative evaluation of the 12 lead ECG. The aim of this study was to assess the system's ability to detect and quantify lateral MI, using cardiac magnetic resonance (CMR) as reference standard. METHODS: In 23 patients with isolated lateral infarctions MI size was assessed by CMR and estimated by QRS scoring. The ECGs were also evaluated by two cardiologists according to clinical routine. RESULTS: The MI size estimated by QRS scoring correlated with MI size assessed by CMR (r=0.55, p=0.006). The sensitivity for lateral MI detection was 78% for QRS scoring and 39% for clinical routine ECG evaluation, respectively. CONCLUSION: Selvester QRS scoring can be used to estimate size of isolated lateral MI and has a higher sensitivity for infarct detection compared to clinical routine evaluation of ECGs in these patients. PMID- 26277445 TI - A kinetic model for the prevalence of mono- over poly-pupylation. AB - Bacteria belonging to the phyla Actinobacteria and Nitrospira possess proteasome cores homologous to the eukaryotic 20S proteasome particle. In these bacteria, the cytoplasmic signal for proteasomal degradation is a small protein termed Pup (prokaryotic ubiquitin-like protein). PafA, the only known Pup ligase, conjugates Pup to lysine side chains of target proteins. In contrast to the eukaryotic ubiquitin-proteasome system, where poly-ubiquitin chains are the principal tags for proteasomal degradation, mono-Pup moieties are almost exclusively observed in vivo and are sufficient as degradation tags. Although Pup presents lysines, raising the possibility of poly-Pup chain assembly, these do not predominate. At present, the factors promoting the distinct predominance of mono- over poly pupylation remain poorly understood. To address this issue, we conducted a detailed biochemical analysis characterizing the pupylation of model proteins in vitro. We found that Pup can indeed serve as a pupylation target for PafA either in its free form or when already conjugated to proteins, thus allowing for the formation of poly-Pup chains. However, our results indicate that pupylation of an already pupylated protein is unlikely to occur due to low affinity of PafA for such species. This alone prevents predominance of poly- over mono-pupylation in vitro. This effect is likely to be magnified in vivo by the combination of PafA kinetics with the high abundance of non-pupylated proteins. Overall, this work provides a kinetic explanation for the prevalence of mono- rather than poly pupylation in vivo, and sheds light on PafA substrate specificity. PMID- 26277446 TI - On the Mechanisms of Hydrogen-Atom Transfer from Water to the Heteronuclear Oxide Cluster [Ga2 Mg2 O5 ](.+) : Remarkable Electronic Structure Effects. AB - Mechanistic insight into the homolytic cleavage of the O-H bond of water by the heteronuclear oxide cluster [Ga2 Mg2 O5 ](.+) has been derived from state-of-the art gas-phase experiments in conjunction with quantum chemical calculations. Three pathways have been identified computationally. In addition to the conventional hydrogen-atom transfer (HAT) to the radical center of a bridging oxygen atom, two mechanistically distinct proton-coupled electron-transfer (PCET) processes have been identified. The energetically most favored path involves initial coordination of the incoming water ligand to a magnesium atom followed by an intramolecular proton transfer to the lone-pair of the bridging oxygen atom. This step, which is accomplished by an electronic reorganization, generates two structurally equivalent OH groups either of which can be liberated, in agreement with labeling experiments. PMID- 26277447 TI - Babesia species in questing Ixodes ricinus, Sweden. AB - Babesiosis is an emerging tick-transmitted zoonosis in large parts of the world. In Sweden, the occurrence and diversity of Babesia species is largely unknown. In order to estimate the exposure to Babesia from infected ticks, we collected questing Ixodes ricinus from several sites across southern Sweden during two consecutive field seasons and investigated the occurrence of Babesia species. We report for the first time the occurrence of the zoonotic species Babesia venatorum in Swedish ticks, with a prevalence of 1%. We also detected B. microti (prevalence 3.2%) and B. divergens (prevalence 0.2%). The incidence of Babesia in questing ticks is substantially lower than that of several other tick-borne diseases in Sweden. Nevertheless, babesiosis should not be neglected as a possible diagnosis following tick bites in humans and animals in Sweden. PMID- 26277448 TI - Low environmental levels of neuro-active pharmaceuticals alter phototactic behaviour and reproduction in Daphnia magna. AB - Assessing the risks of emerging contaminants, such as pharmaceuticals in the environment requires an understanding of their exposure regime and their effects at environmentally relevant concentrations across species. Daphnia magna represents an excellent invertebrate model species to study the mode of action of emerging pollutants, allowing the assessment of effects at different biological levels. The present study aims to test the hypothesis that different families of neuro-active pharmaceuticals at low environmentally relevant concentrations may lead to similar phenotypic responses in D. magna. Phenotypic traits included reproduction and behavioural responses. Selected pharmaceuticals were carbamazepine, diazepam and propranolol, three widely prescribed compounds, already detected at considerable levels in the environment (ng to few MUg/L). Fluoxetine was also included in behavioural assays. The three tested neuro-active pharmaceuticals were able to enhance reproduction at 1ng/L of propranolol, 0.1MUg/L of diazepam and 1MUg/L of carbamazepine. Fluoxetine, carbamazepine and diazepam increased positive phototactic behaviour at concentrations ranging from 1, 10 and 100ng/L, respectively. Reported responses were nonmonotonic, which means that eco-toxicity testing of pharmaceuticals need to assess effects at the ng/L range. PMID- 26277450 TI - Gastric bypass-induced weight loss alters obesity-associated patterns of plasma pentraxin-3 and systemic inflammatory markers. AB - BACKGROUND: Systemic inflammation contributes to obesity-associated complications. The short pentraxin C-reactive protein (CRP) is a validated inflammatory marker, whereas long pentraxin-3 (PTX3) limits inflammation and is adaptively stimulated by proinflammatory cytokines in vitro. Severely obese (SO) patients (body mass index [BMI]>40] have the highest obesity-associated complications and increasingly undergo surgical treatment. SO-associated changes in plasma PTX3 and their interactions with systemic inflammation are, however, unknown. OBJECTIVE: We sought to determine potential alterations in plasma PTX3 and their associations with changes in inflammatory markers before and after weight loss induced by laparoscopic Roux-en-Y gastric bypass (LRYGB). SETTING: University hospital in Trieste, Italy. METHODS: Plasma PTX3, CRP, and cytokines, including tumor necrosis factor alpha and interleukin 6 were measured in (1) 24 individuals with severe, class III obesity (SO; age = 42 +/- 1 yr, female/male = 18/6, BMI = 45 +/- 1 kg/m(2)) before and 3, 6, and 12 months after LRYGB; and (2) age- and sex-matched normal-weight (N; n = 56, BMI = 22 +/- .2 kg/m(2)) or class I obese individuals (O; n = 44, BMI = 31.2 +/- .3 kg/m(2)). RESULTS: SO, but not O, had higher plasma PTX3 compared with N, associated with highest proinflammatory cytokines and CRP (P<.05 versus N-O). In all patients, plasma interleukin 6 and tumor necrosis factor alpha were associated positively with PTX3 (P<.05). Plasma CRP and proinflammatory cytokines declined during LRYGB induced weight loss. In contrast, high PTX3 further increased and remained elevated (P<.05 versus basal). CONCLUSIONS: Obesity level and energy balance modulate interactions between PTX3 and systemic inflammation. Elevated PTX3 is a novel, potentially adaptive alteration associated with proinflammatory cytokines in SO. Their differential changes conversely suggest circulating PTX3 as a novel negative inflammatory marker in SO undergoing LRYGB-induced weight loss. PMID- 26277449 TI - Super-enhancers: Asset management in immune cell genomes. AB - Super-enhancers (SEs) are regions of the genome consisting of clusters of regulatory elements bound with very high amounts of transcription factors, and this architecture appears to be the hallmark of genes and noncoding RNAs linked with cell identity. Recent studies have identified SEs in CD4(+) T cells and have further linked these regions to single nucleotide polymorphisms (SNPs) associated with immune-mediated disorders, pointing to an important role for these structures in the T cell differentiation and function. Here we review the features that define SEs, and discuss their function within the broader understanding of the mechanisms that define immune cell identity and function. We propose that SEs present crucial regulatory hubs, coordinating intrinsic and extrinsic differentiation signals, and argue that delineating these regions will provide important insight into the factors and mechanisms that define immune cell identity. PMID- 26277451 TI - Depression and quality of life in Spanish-speaking immigrant persons with epilepsy compared with those in English-speaking US-born persons with epilepsy. AB - OBJECTIVE: This study aimed to examine levels of depression and quality of life in Spanish-speaking (less acculturated) immigrants with epilepsy compared with those in English-speaking US-born persons with epilepsy (PWEs). METHODS: The study included 85 PWEs - 38 Spanish-speaking immigrants with epilepsy and 47 US born PWEs. All patients underwent video-EEG monitoring and completed depression and quality-of-life inventories in their dominant language (Spanish/English). Chart review of clinical epilepsy variables was conducted by an epileptologist. RESULTS: Our study revealed that depression scores were significantly higher in Hispanic PWEs (21.65+/-14.6) than in US-born PWEs (14.50+/-10.2) (t (64.02)=-2.3, two-sided p=.025). Marital status, medical insurance, antidepressant use, seizure frequency, and number of antiepileptic drugs (AEDs) were tested as covariates in the ANCOVA framework and were not statistically significant at the 0.05 significance level. Fewer Hispanics were prescribed antidepressant medications (13.15% for Hispanics and 40.42% for US-born, chi(2) (1,85) 7.71, p=.005) and had access to comprehensive health insurance coverage (chi(2) (1,85)=13.70, p=0.000). Hispanic patients were also found to be receiving significantly less AEDs compared with their US-born peers (t (83, 85)=2.33, p=.02). Although quality of life was diminished in both groups, Seizure Worry was worse for Hispanics after accounting for potential effects of marital status, medical insurance, use of antidepressants, seizure frequency, and number of antiepileptic drugs (AEDs) ((1, 83), F=7.607, p=0.007). SIGNIFICANCE: The present study is the first of its kind to examine depression and quality of life in Spanish-speaking US immigrants with epilepsy. Spanish-speaking immigrants with epilepsy have been identified as a group at risk. They demonstrated higher depression scores and more Seizure Worry independent of epilepsy and demographic characteristics compared with their US born peers. The Hispanic group was receiving less treatment for depression, was taking less AEDs, and had less access to comprehensive health coverage compared with non-Hispanics. PMID- 26277452 TI - Rare Upper Airway Anomalies. AB - A broad spectrum of congenital upper airway anomalies can occur as a result of errors during embryologic development. In this review, we will describe the clinical presentation, diagnosis, and management strategies for a few select, rare congenital malformations of this system. The diagnostic tools used in workup of these disorders range from prenatal tests to radiological imaging, swallowing evaluations, indirect or direct laryngoscopy, and rigid bronchoscopy. While these congenital defects can occur in isolation, they are often associated with disorders of other organ systems or may present as part of a syndrome. Therefore workup and treatment planning for patients with these disorders often involves a team of multiple specialists, including paediatricians, otolaryngologists, pulmonologists, speech pathologists, gastroenterologists, and geneticists. PMID- 26277455 TI - Color stability and force decay of clear orthodontic elastomeric chains: An in vitro study. AB - OBJECTIVE: To compare the percentage force decay of clear and semi-clear elastomeric chain products from eight different manufacturers and to evaluate the amount of discoloration after immersion in colored dietary media of the same elastomeric chain products. MATERIAL AND METHODS: An in vitro study was designed using an electronic force gauge to measure six samples from each of 19 types of elastomeric chains stretched for a period of four weeks. A spectrophotometer was used to measure the color of each specimen (10 of each type) at baseline and after being soaked in a dietary medium (coffee, tea, cola, and wine in 250 ml amounts) for 72 h. RESULTS: There was a significant difference in the percentage of the lost initial force between all the tested E-chains (P<0.001). ANOVA shows a significant difference in the amount of discoloration between the E-chain types (P<0.001). Semi-clear (tooth-color/pearl/obscure) E-chain types (TP-ToothC, OrthO Pearl, GAC-SiliPearl, 3M-Obscure) present significantly less change in color than clear E-chains of the same brand (TP-Clear, OrthoO-Clear, GAC-SiliClear, 3M Clear). CONCLUSIONS: Significant differences in the mean percentage force decay between the 19 studied clear elastomeric chain types were present. AO-Memory and Ormco maintained most of their original force at the end of the four-week interval. Significant differences in discoloration also exist between the various types of E-chains. TP Orthodontics (Tooth-Colored, SuperSlick, Clear) and Ortho Organizers (Pearl) showed the least discoloration. PMID- 26277457 TI - Adjustable selective maxillary expansion combined with maxillomandibular surgery: A case report. AB - BACKGROUND: Surgically assisted rapid maxillary expansion (SARME) is usually considered the gold standard for maxillary transverse expansion in adults. However, a second surgical procedure is needed in cases of associated sagittal or vertical discrepancies. We describe the use of two new innovative devices for the correction of discrepancies in all dimensions during a single surgical procedure, thus reducing treatment duration. MATERIAL: We report the case of a 21-year-old female patient, referred to our department for skeletal Class III malocclusion associated with right-side laterognathism and transverse maxillary deficiency. The patient underwent one-stage surgery, using sliding osteosynthesis plates and an adjustable bone-borne distractor. Pre-surgical orthodontics consisted in leveling and aligning the mandibular arch; maxillary leveling was initiated 3 months before surgery. Postoperative palatal distraction combined with orthodontic finishing enabled complete correction of dental and bony discrepancies after 3 months. CONCLUSION: In our experience, treatment of transverse, sagittal and vertical discrepancies has been possible in a single surgical procedure, using two innovative techniques: sliding osteosynthesis and an adjustable bone distractor. Two years post-surgery, the correction is stable in all dimensions. PMID- 26277458 TI - Bone stress and strain modification in diastema closure: 3D analysis using finite element method. AB - The aim of this study was to analyse the stress and strain distribution in the alveolar bone between two central incisors in the process of diastema closure with a constant force. A 3-dimensional computer modeling based on finite element techniques was used for this purpose. A model of an anterior segment of the mandible containing cortical bone, spongy bone, gingivae, PDL and two central incisors with a bracket in the labial surface of each tooth were designed. The von Mises stress and strain was evaluated in alveolar bone along a path of nodes defined in a cresto-apical direction in the midline between two teeth. It was observed that stress and strain of alveolar bone increased in midline with a constant force to close the diastema regardless of the type of movement in gradual steps of diastema closure, however the stress was higher in the tipping movement than the bodily so it can be suggested that a protocol of force system modification should be introduced to compensate for the stress and strain changes caused by the reduced distance to avoid the unwanted stress alteration during the diastema closure. PMID- 26277459 TI - Personal semantics: Is it distinct from episodic and semantic memory? An electrophysiological study of memory for autobiographical facts and repeated events in honor of Shlomo Bentin. AB - Declarative memory is thought to consist of two independent systems: episodic and semantic. Episodic memory represents personal and contextually unique events, while semantic memory represents culturally-shared, acontextual factual knowledge. Personal semantics refers to aspects of declarative memory that appear to fall somewhere in between the extremes of episodic and semantic. Examples include autobiographical knowledge and memories of repeated personal events. These two aspects of personal semantics have been studied little and rarely compared to both semantic and episodic memory. We recorded the event-related potentials (ERPs) of 27 healthy participants while they verified the veracity of sentences probing four types of questions: general (i.e., semantic) facts, autobiographical facts, repeated events, and unique (i.e., episodic) events. Behavioral results showed equivalent reaction times in all 4 conditions. True sentences were verified faster than false sentences, except for unique events for which no significant difference was observed. Electrophysiological results showed that the N400 (which is classically associated with retrieval from semantic memory) was maximal for general facts and the LPC (which is classically associated with retrieval from episodic memory) was maximal for unique events. For both ERP components, the two personal semantic conditions (i.e., autobiographical facts and repeated events) systematically differed from semantic memory. In addition, N400 amplitudes also differentiated autobiographical facts from unique events. Autobiographical facts and repeated events did not differ significantly from each other but their corresponding scalp distributions differed from those associated with general facts. Our results suggest that the neural correlates of personal semantics can be distinguished from those of semantic and episodic memory, and may provide clues as to how unique events are transformed to semantic memory. PMID- 26277460 TI - Functional asymmetry between the left and right human fusiform gyrus explored through electrical brain stimulation. AB - The ventral temporal cortex (VTC) contains several areas with selective responses to words, numbers, faces, and objects as demonstrated by numerous human and primate imaging and electrophysiological studies. Our recent work using electrocorticography (ECoG) confirmed the presence of face-selective neuronal populations in the human fusiform gyrus (FG) in patients implanted with intracranial electrodes in either the left or right hemisphere. Electrical brain stimulation (EBS) disrupted the conscious perception of faces only when it was delivered in the right, but not left, FG. In contrast to our previous findings, here we report both negative and positive EBS effects in right and left FG, respectively. The presence of right hemisphere language dominance in the first, and strong left-handedness and poor language processing performance in the second case, provide indirect clues about the functional architecture of the human VTC in relation to hemispheric asymmetries in language processing and handedness. PMID- 26277461 TI - Outcomes of pulmonary resection in single-lung patients. AB - BACKGROUND: After pneumonectomy, the development of a new lung cancer or a recurrence in the residual lung is a challenge. Surgery often is considered contraindicated. The goal of our study is to assess the morbidity and mortality of lung resection on a single lung. METHODS: All patients who underwent lung resection after pneumonectomy from January 1996 through December 2012 were reviewed. RESULTS: There were 12 patients (10 men and 2 women). Mean age was 71 years (range, 54-81 years). Mean preoperative FEV1 was 1,470 ml (52%) and preoperative FVC 2,153 ml (61,5%). Subsequent pulmonary resection was performed after a median follow-up of 34,5 months. Wedge resection was performed in all patients. Diagnosis was pulmonary mestastatic lung cancer in 2 patients, metachronous lung cancer in 6, metastatic extrathoracic cancer in 3 and benign nodule in one. Complications occurred in 4 patients (33,4%) while operative mortality was nil. CONCLUSIONS: Lung resection on a single lung is a safe procedure associated with acceptable morbidity and mortality. Careful patient selection is very important. PMID- 26277462 TI - Of mice and men and surgical transcatheter aortic valve insertion. PMID- 26277464 TI - Pulmonary vein stenosis: Challenges ahead. PMID- 26277463 TI - Device success and 30-day clinical outcome in patients undergoing preimplant valvuloplasty in transfemoral versus omitting valvuloplasty in transapical transcatheter aortic valve replacement. AB - OBJECTIVES: The study objective was to evaluate the impact of preimplantation balloon valvuloplasty on procedural outcomes in high-risk or no-option patients with aortic stenosis undergoing Edwards Lifesciences (Irvine, Calif) Sapien valve placement. Paravalvular aortic regurgitation has been associated with long-term mortality after transcatheter aortic valve replacement. Whether omitting preimplant balloon valvuloplasty affects paravalvular aortic regurgitation after Edwards Sapien transcatheter aortic valve replacement is currently unknown. METHODS: We retrospectively analyzed the clinical outcome of 121 consecutive patients undergoing transapical (N = 50) or transfemoral (N = 71) Edwards Sapien transcatheter aortic valve replacement. Routinely, no preimplant balloon valvuloplasty was performed in transapical procedure as opposed to uniform preimplant balloon valvuloplasty in transfemoral cases. The incidence and severity of total and paravalvular aortic regurgitation and 30-day clinical outcomes were compared between the 2 cohorts. RESULTS: The average patient's age was 84.4 years, with a higher prevalence of smoking history (68% vs 42%, P = .005) and peripheral vascular disease (38% vs 20%, P = .03) in the patients undergoing transapical replacement. The preprocedural transthoracic echocardiographic and computed tomography findings were similar between the 2 cohorts. After transcatheter aortic valve replacement, the incidence of mild to moderate total aortic regurgitation (42% transfemoral vs 38% transapical), paravalvular aortic regurgitation (39% transfemoral vs 30% transapical), device success (88.7% transfemoral vs 94.0% transapical), and 30-day composite end points (9.9% transfemoral vs 14.0% transapical) were comparable in both groups. Multivariate regression analysis revealed male gender (odds ratio, 2.7; 95% confidence interval, 1.18-6.35; P = .02) but not preimplant balloon valvuloplasty as an independent predictor for mild or greater total aortic regurgitation. CONCLUSIONS: Compared with transapical transcatheter aortic valve replacement without preimplant balloon valvuloplasty, preimplant balloon valvuloplasty before transfemoral transcatheter aortic valve replacement resulted in a similar degree of prosthesis-related regurgitation, device success, and 30-day composite safety outcomes. PMID- 26277465 TI - Small incisions in small patients: Continued advancement in pediatric thoracoscopy. PMID- 26277467 TI - Dealing with a stenotic bicuspid aortic valve: Is this still an off-label procedure for a sutureless valve? PMID- 26277466 TI - Knowledge, attitudes, and practice preferences of Canadian cardiac surgeons toward the management of acute type A aortic dissection. AB - OBJECTIVES: The complexity of surgical treatment for acute type A dissection contributes to the variability in patient management. This study was designed to elucidate the contemporary practice preferences of cardiac surgeons regarding different phases of management of acute type A aortic dissection. METHODS: A 34 item questionnaire was distributed to all Canadian adult cardiac surgeons addressing the preoperative, intraoperative, and postoperative management of acute type A dissection. A total of 100 responses were obtained (82% of active surgeons in Canada). Outcomes were compared between high- and low-volume aortic surgeons. RESULTS: Seventy-six percent of respondents favored axillary artery cannulation. High-volume surgeons (>150 cases) were more likely to indicate a target lowest nasopharyngeal temperature more than 20 degrees C (53% vs 25%, P = .02). The majority of surgeons (65%) recommended using selective antegrade cerebral perfusion, with a significantly greater proportion for higher-volume aortic surgeons (P = .03). In addition, high-volume aortic surgeons were more likely to recommend aortic root replacement at smaller diameters (73% vs 55%, P = .02), to recommend more extensive distal aortic resection with routine open hemiarch anastomosis (85% vs 65%, P = .04), and to more commonly perform total arch reconstruction when needed (93% vs 77%, P = .04). In the follow-up period, frequency of serial imaging of the residual aorta was significantly higher for high-volume aortic surgeons (P = .04). CONCLUSIONS: This study identified some commonalities in practice preferences among Canadian cardiac surgeons for the management of acute type A aortic dissection. However, it also highlighted significant differences in temperature management, cerebral protection strategies, and extent of resection between high-volume and low-volume aortic surgeons. PMID- 26277468 TI - Surgical removal of embolized atrial septal defect device from pulmonary artery. PMID- 26277469 TI - Contemporary outcomes of surgery for aortic root aneurysms: A propensity-matched comparison of valve-sparing and composite valve graft replacement. PMID- 26277470 TI - Descending thoracic and thoracoabdominal aortic aneurysms: "Busted". PMID- 26277471 TI - Stem cells on a new stage: Treatment of hypoplastic left heart syndrome. PMID- 26277472 TI - Impact of off-pump coronary artery bypass grafting on long-term percutaneous coronary interventions. AB - OBJECTIVES: The debate regarding the advantages and limitations of off-pump versus on-pump coronary artery bypass grafting (CABG) has yet to be resolved. This study was designed to compare the impact of surgical technique on long-term mortality and subsequent revascularization. METHODS: The Predicting Long-Term Outcomes After Isolated Coronary Artery Bypass Surgery (PRIORITY) project was designed to evaluate the long-term outcomes of 2 large, prospective multicenter cohort studies on CABG conducted in Italy between 2002 and 2004 and in 2007 and 2008. Clinical data on isolated CABG were compiled from 2 administrative databases. RESULTS: The study population consisted of 11,021 patients who underwent isolated CABG (27.2% off-pump CABG). Surgical strategy did not affect in-hospital mortality. Multivariate logistic regression demonstrated that on-pump CABG was the only factor that protected from in-hospital percutaneous coronary intervention after surgery (odds ratio, 0.61). Although unadjusted long-term survival was significantly worse for off-pump CABG, adjustment did not confirm off-pump CABG as a risk factor for mortality (hazard ratio, 0.96; 95% confidence interval, 0.87-1.06). The on-pump CABG group had a significantly lower hospitalization for subsequent percutaneous coronary intervention, a finding confirmed even with adjustment for confounding factors (hazard ratio, 0.70; 95% confidence interval, 0.62-0.80; P < .001). Off-pump CABG thus carried a 42% higher risk for subsequent percutaneous coronary intervention than on-pump CABG. The incidence of repeat CABG was similar between groups. CONCLUSIONS: This study demonstrated that off-pump OPCAB did not affect short- and long-term mortality, but it was a significant risk factor for rehospitalization for percutaneous coronary intervention. PMID- 26277473 TI - Ross procedure in the setting of anomalous aortic origin of a coronary artery. PMID- 26277474 TI - Modified technique for tracheobronchial Y-stent insertion using flexible bronchoscope for stent guidance. PMID- 26277475 TI - Biomechanical drawbacks of different techniques of mitral neochordal implantation: When an apparently optimal repair can fail. AB - OBJECTIVES: Intraoperative assessment of the proper neochordal length during mitral plasty may be complex sometimes. Patient-specific finite element models were used to elucidate the biomechanical drawbacks underlying an apparently correct mitral repair for isolated posterior prolapse. METHODS: Preoperative patient-specific models were derived from cardiac magnetic resonance images; integrated with intraoperative surgical details to assess the location and extent of the prolapsing region, including the number and type of diseased chordae; and complemented by the biomechanical properties of mitral leaflets, chordae tendineae, and artificial neochordae. We investigated postoperative mitral valve biomechanics in a wide spectrum of different techniques (single neochorda, double neochordae, and preconfigured neochordal loop), all reestablishing adequate valvular competence, but differing in suboptimal millimetric expanded polytetrafluoroethylene suture lengths in a range of +/-2 mm, compared with the corresponding "ideal repair." RESULTS: Despite the absence of residual regurgitation, alterations in chordal forces and leaflet stresses arose simulating suboptimal repairs; alterations were increasingly relevant as more complex prolapse anatomies were considered and were worst when simulating single neochorda implantation. Multiple chordae implantations were less sensitive to errors in neochordal length tuning, but associated postoperative biomechanics were hampered when asymmetric configurations were reproduced. Computational outcomes were consistent with the presence and entity of recurrent mitral regurgitation at midterm follow-up of simulated patients. CONCLUSIONS: Suboptimal suture length tuning significantly alters chordal forces and leaflet stresses, which may be key parameters in determining the long-term outcome of the repair. The comparison of the different simulated techniques suggests possible criteria for the selection and implementation of neochordae implantation techniques. PMID- 26277476 TI - Assessment of mitral annuloplasty ring by cardiac computed tomography: Correlation with echocardiographic parameters and comparison between two different ring types. AB - OBJECTIVES: This study investigated computed tomographic (CT) appearance after mitral ring annuloplasty, especially comparing CT findings between patients with normal pressure gradient (PG) and patients with functional mitral stenosis (MS) and between 2 commonly used types of annuloplasty ring. METHODS: A total of 45 cardiac CT scans in patients who underwent mitral ring annuloplasty (Carpentier Edwards ring, n = 27; Duran ring, n = 18) were retrospectively reviewed. On CT scan, presence of significant pannus around the annuloplasty ring, presence of leaflet thickening, and maximal mitral opening area were analyzed. CT findings were compared between patients with normal PG and patients with functional MS (mean diastolic PG >= 5 mm Hg). Incidences of functional MS and CT findings were compared between ring types. RESULTS: Significant pannus was present in 10 cases and leaflet thickening in 31 cases, and maximal opening area was 2.34 +/- 0.717 cm(2). Valve opening area on CT was positively correlated with mitral valve area on transthoracic echocardiography and negatively correlated with mean diastolic PG. Mean diastolic PG was significantly elevated with increasing pannus severity. Patients with functional MS had more significant pannus than patients with normal PG. The Duran ring group had higher mean diastolic PG, smaller mitral valve area, and higher incidence of functional MS than the Carpentier-Edwards ring group (P < .05). The proportion of pannus and significant pannus was significantly higher in the Duran ring group (P < .05). CONCLUSIONS: Significant pannus around the annuloplasty ring on CT may cause functional MS after mitral ring annuloplasty. This may occur more frequently with the Duran ring. PMID- 26277477 TI - Chelation efficacy and erythroid response during deferasirox treatment in patients with myeloproliferative neoplasms in fibrotic phase. AB - At present, very few data are available on deferasirox (DFX) in the treatment of patients with Philadelphia-negative myeloproliferative neoplasms in fibrotic phase (FP-MPN) and transfusion dependence. To address this issue, a retrospective analysis of 28 patients (22 male and 6 female) with FP-MPN and iron overload secondary to transfusion dependence was performed, based on patients enrolled in the database of our regional cooperative group who received treatment with DFX. DFX was started after a median interval from diagnosis of 12.8 months (IR 7.1 43.1) with median ferritin values of 1415 ng/mL (IR 1168-1768). Extra hematological toxicity was reported in 16 of 28 patients (57.1%), but only two patients discontinued treatment due to toxicity. Among 26 patients evaluable for response (>=6 months of treatment), after a median treatment period of 15.4 months (IR 8.1-22.3), 11 patients (42.3%) achieved a stable and consistent reduction in ferritin levels <1000 ng/mL. As for hematological improvement, 6 of 26 patients (23%) showed a persistent (>3 months) rise of Hb levels >1.5 g/dL, with disappearance of transfusion dependence in four cases. Treatment with DFX is feasible and effective in FP-MPN with iron overload. Moreover, in this setting, an erythroid response can occur in a significant proportion of patients. PMID- 26277478 TI - Rethinking the Concepts of Fluence (UV Dose) and Fluence Rate: The Importance of Photon-based Units - A Systemic Review. AB - After a critical review of the fundamental equations describing photobiological and photochemical processes occurring in a medium exposed to a quasi-collimated monochromatic UV light beam, the analysis in this review is extended to analogous processes driven by polychromatic UV light, such as that emitted by medium pressure mercury-vapor arc lamps. The analysis is based on the Second Law of Photochemistry, namely that all photochemical events must be independent, and the rate of such events must be proportional to the rate of photon absorption. A consistent application of the Second Law of Photochemistry leads to a concept change; hence it is proposed herein to use photon fluence and photon fluence rate, rather than fluence (UV dose) and fluence rate, respectively, in the analysis and interpretation of photobiological and photochemical processes. As a consequence, many equations that have been used in the past must be revised, and some experimental information (e.g. action spectra) needs to be re-analyzed. PMID- 26277479 TI - Progesterone receptor-estrogen receptor crosstalk: a novel insight. AB - Copy number loss of the PGR gene and decreased expression of progesterone receptor (PR) may account for worse clinical outcomes in some individuals with estrogen receptor alpha (ERalpha)-positive breast cancer. A recent report shows that PR activation inhibits estrogen-driven breast tumor growth by altering ERalpha chromatin binding and transcriptional activity. PMID- 26277480 TI - Mixtures of amino-acid based ionic liquids and water. AB - New ionic liquids (ILs) involving increasing numbers of organic and inorganic ions are continuously being reported. We recently developed a new force field; in the present work, we applied that force field to investigate the structural properties of a few novel imidazolium-based ILs in aqueous mixtures via molecular dynamics (MD) simulations. Using cluster analysis, radial distribution functions, and spatial distribution functions, we argue that organic ions (imidazolium, deprotonated alanine, deprotonated methionine, deprotonated tryptophan) are well dispersed in aqueous media, irrespective of the IL content. Aqueous dispersions exhibit desirable properties for chemical engineering. The ILs exist as ion pairs in relatively dilute aqueous mixtures (10 mol%), while more concentrated mixtures feature a certain amount of larger ionic aggregates. PMID- 26277481 TI - The inhibitory effects of quercetin on obesity and obesity-induced inflammation by regulation of MAPK signaling. AB - Quercetin is a flavonoid found in fruits, vegetables, leaves and grains. It has inhibitory, antiviral, antiasthma, anticancer and antiinflammatory effects. Research has suggested that obesity is linked to metabolic disorders. In this study, we examined the inhibitory effect of quercetin on lipid accumulation and obesity-induced inflammation using 3T3-L1, RAW264.7, zebrafish and mouse models. Quercetin suppressed protein levels of the key adipogenic factors C/EBPbeta, C/EBPalpha, PPARgamma and FABP4 and the TG-synthesis enzymes lipin1, DGAT1 and LPAATtheta. Activation of m-TOR and p70S6K, which are related to insulin and adipogenesis, was down-regulated during adipogenesis in 3T3-L1 cells. Recent research suggested that MAPK signaling factors were involved in adipogenesis and inflammation and that the adipokines MCP-1 and TNF-alpha attracted macrophages into adipose tissue. Our data showed that quercetin inhibited the MAPK signaling factors ERK1/2, JNK and p38MAPK and MCP-1 and TNF-alpha in adipocytes and macrophages. Quercetin also inhibited secretion of the inflammatory cytokines IL 1beta and IL-6 and stimulated that of IL-10, an antiinflammatory cytokine. In this study, we confirmed the inhibitory effects of quercetin in adipogenesis and inflammation using a mouse model. In mice, quercetin reduced body weight (almost 40%) and suppressed expression of adipogenic, lipogenic and inflammation-related cytokines. Our data demonstrated that quercetin inhibits lipid accumulation and obesity-induced inflammation in the cell and animal models. Our study suggested that quercetin may represent a potential therapeutic agent for other metabolic disorders by regulating obesity and obesity-induced inflammation. PMID- 26277483 TI - Tumor infiltration pattern into the surrounding tissue has prognostic significance in advanced gastric cancer. AB - Gastric cancer can be classified into three subgroups according to pattern of tumor infiltration into the surrounding tissue: INFa (expanding growth and a distinct border with the surrounding tissue), INFc (infiltrating growth and an indistinct border with the surrounding tissue), and INFb (in-between a and c). How the tumor infiltration pattern (INF) relates to prognosis and type of recurrence in advanced gastric cancer has not been sufficiently explored. We examined 805 consecutive advanced gastric adenocarcinoma patients who underwent curative gastrectomy at our institution between 1980 and 2005. Poor differentiation, serosal invasion, and lymph node metastasis were significantly more frequent in patients with INFc tumors than in those with INFa/b tumors. For patients with a T2 or T3 tumor, there was no significant difference in prognosis between those with INFa/b and with INFc. However, for patients with a T4a or T4b tumor, the prognosis of those with INFc was significantly worse than that of those with INFa/b. In multivariate analysis, INF was an independent prognostic indicator in T4a but not T2, T3, and T4b. Furthermore, the prognosis of T4 patients with INFc tumors was significantly worse than that of those with INFa/b, especially in node-negative but not in node-positive cases. In patients with a T4a or T4b tumor, peritoneal recurrence was significantly more frequent for those with INFc than for those with INFa/b. Our data indicate that INF is useful to predict the prognosis and recurrence pattern in T4a node-negative gastric cancer. PMID- 26277482 TI - Marijuana, phytocannabinoids, the endocannabinoid system, and male fertility. AB - Marijuana has the highest consumption rate among all of the illicit drugs used in the USA, and its popularity as both a recreational and medicinal drug is increasing especially among men of reproductive age. Male factor infertility is on the increase, and the exposure to the cannabinoid compounds released by marijuana could be a contributing cause. The endocannabinoid system (ECS) is deeply involved in the complex regulation of male reproduction through the endogenous release of endocannabinoids and binding to cannabinoid receptors. Disturbing the delicate balance of the ECS due to marijuana use can negatively impact reproductive potential. Various in vivo and in vitro studies have reported on the empirical role that marijuana plays in disrupting the hypothalamus pituitary-gonadal axis, spermatogenesis, and sperm function such as motility, capacitation, and the acrosome reaction. In this review, we highlight the latest evidence regarding the effect of marijuana use on male fertility and also provide a detailed insight into the ECS and its significance in the male reproductive system. PMID- 26277485 TI - Mechanical properties of the trapezius during scapular elevation in people with chronic whiplash associated disorders--A case-control ultrasound speckle tracking analysis. AB - BACKGROUND: Approximately 50% of people with Whiplash Associated Disorders (WAD) report longstanding symptoms. The upper trapezius is commonly painful yet its mechanical properties are not fully understood. OBJECTIVES: This study examined the deformation of different depths of the upper trapezius muscle during a scapular elevation task (shoulder shrugging) before and following loaded arm abduction. DESIGN AND METHODS: A cross-sectional case-control study of 36 people (26 female and 10 male, mean age 38 (SD 11)) with chronic WAD and 36 controls, matched for age and gender. Real-time ultrasound recordings of upper trapezius were taken during both scapular elevation tasks. Post-process speckle tracking analysis was undertaken of three different sections of the upper trapezius muscle (superficial, middle, deep). RESULTS: The WAD group had lower deformation of the superficial section of the upper trapezius compared to the control group in both concentric and eccentric phases of scapular elevation (p < 0.05) especially before the loaded arm abduction. After arm abduction, the deformation of the trapezius was reduced in both groups but only significantly in the WAD-group (p = 0.03). Within-group analysis revealed that the control group least engaged the deep section of upper trapezius during the task (p < 0.01). CONCLUSION: This study, measuring mechanical deformation of the upper trapezius during a scapular elevation task indicates that persons with WAD may display different patterns in engagement of the muscle sections than those in the control group. Further research is needed to replicate and understand the reasons for and implications of this possible change in motor strategy within upper trapezius. Clinical Trials.gov, Number: NCT01547624. PMID- 26277484 TI - Vascular Smooth Muscle as a Target for Novel Therapeutics. AB - Cardiovascular disease is the principal cause of death in patients with type 2 diabetes (T2DM). Exposure of the vasculature to metabolic disturbances leaves a persistent imprint on vascular walls, and specifically on smooth muscle cells (SMC) that favours their dysfunction and potentially underlies macrovascular complications of T2DM. Current diabetes therapies and continued development of newer treatments has led to the ability to achieve more efficient glycaemic control. There is also some evidence to suggest that some of these treatments may exert favourable pleiotropic effects, some of which may be at the level of SMC. However, emerging interest in epigenetic markers as determinants of vascular disease, and a putative link with diabetes, opens the possibility for new avenues to develop robust and specific new therapies. These will likely need to target cell-specific epigenetic changes such as effectors of DNA histone modifications that promote or inhibit gene transcription, and/or microRNAs capable of regulating entire cellular pathways through target gene repression. The growing epidemic of T2DM worldwide, and its attendant cardiovascular mortality, dictates a need for novel therapies and personalised approaches to ameliorate vascular complications in this vulnerable population. PMID- 26277486 TI - Does Educator Training or Experience Affect the Quality of Multiple-Choice Questions? AB - RATIONALE AND OBJECTIVES: Physicians receive little training on proper multiple choice question (MCQ) writing methods. Well-constructed MCQs follow rules, which ensure that a question tests what it is intended to test. Questions that break these are described as "flawed." We examined whether the prevalence of flawed questions differed significantly between those with or without prior training in question writing and between those with different levels of educator experience. MATERIALS AND METHODS: We assessed 200 unedited MCQs from a question bank for our senior medical student radiology elective: an equal number of questions (50) were written by faculty with previous training in MCQ writing, other faculty, residents, and medical students. Questions were scored independently by two readers for the presence of 11 distinct flaws described in the literature. RESULTS: Questions written by faculty with MCQ writing training had significantly fewer errors: mean 0.4 errors per question compared to a mean of 1.5-1.7 errors per question for the other groups (P < .001). There were no significant differences in the total number of errors between the untrained faculty, residents, and students (P values .35-.91). Among trained faculty 17/50 questions (34%) were flawed, whereas other faculty wrote 38/50 (76%) flawed questions, residents 37/50 (74%), and students 44/50 (88%). Trained question writers' higher performance was mainly manifest in the reduced frequency of five specific errors. CONCLUSIONS: Faculty with training in effective MCQ writing made fewer errors in MCQ construction. Educator experience alone had no effect on the frequency of flaws; faculty without dedicated training, residents, and students performed similarly. PMID- 26277487 TI - Functions of the anterior insula in taste, autonomic, and related functions. AB - The anterior insula contains the primary taste cortex, in which neurons in primates respond to different combinations providing a distributed representation of different prototypical tastes, oral texture including fat texture, and oral temperature. These taste neurons do not represent food reward value, in that feeding to satiety does not reduce their responses to zero, in contrast to the next stage of processing, the orbitofrontal cortex, where food reward value is represented. Corresponding results are found with fMRI in humans. A more ventral part of the anterior insula is implicated using fMRI in autonomic-visceral functions. 'Salient' stimuli, including rewarding, punishing, non-rewarding, and novel stimuli may activate this viscero-autonomic system, via inputs received from regions that represent these stimuli such as the orbitofrontal and anterior cingulate cortex. More posteriorly in the insula, there is an oral somatosensory region, and posterior to this somatosensory regions that respond to touch to the body. These taste and somatosensory representations in the insula provide representations that are about the external world (touch), are intermediate (oral taste and texture), and are about internal signals related to visceral and autonomic function. This functionality needs to be taken into account when considering activations of the insula found in cognitive tasks. PMID- 26277488 TI - Prediction of dual agents as an activator of mutant p53 and inhibitor of Hsp90 by docking, molecular dynamic simulation and virtual screening. AB - Heat shock protein90s (Hsp90s) play a crucial role in the development of cancer, and their inhibitors are a main target for tumor suppression. P53 also is a tumor suppressor, but in cancer cells, mutations in the p53 gene lead to the inactivation and accumulation of protein. For instance, the ninth p53 cancer mutation, Y220C, destabilizes the p53 core domain. Small molecules have been assumed to bind to Y220C DNA-binding domain and reactivate cellular mutant p53 functions. In this study, one of the mutant p53 activators is suggested as an Hsp90 inhibitor according to a pyrazole scaffold. To confirm a new ligand as a dual agent, molecular docking and molecular dynamic simulations were performed on both proteins (p53 and Hsp90). Molecular dynamic simulations were also conducted to evaluate the obtained results on the other two pyrazole structures, one known as Hsp90 inhibitor and the other as the reported mutant p53 activator. The findings indicate that the new ligand was stable in the active site of both proteins. Finally, a virtual screening was performed on ZINC database, and a set of new dual agents was proposed according to the new ligand scaffold. PMID- 26277489 TI - Ethnobotany, therapeutic value, phytochemistry and conservation status of Bowiea volubilis: A widely used bulbous plant in southern Africa. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Bowiea volubilis Harv. ex Hook.f. (Family: Asparagaceae) is a bulbous medicinal plant widely used against numerous ailments including headache, muscular pains, infertility, cystitis and venereal diseases in southern Africa. AIM OF THE REVIEW: To provide a critical and updated review of Bowiea volubilis with regards to its abundance, medicinal importance, conservation status and potential means to sustain its availability for future generations. METHODS: A comprehensive literature search using online databases such as Web of Science, Google Scholar, Scopus and Springerlink as well as ethnobotanical literature was done in order to obtain, collate, synthesize and critically analyze available information on Bowiea volubilis. RESULTS: On the basis of its wide distribution in many Provinces in South Africa, Bowiea volubilis has a long history of applications among the different ethnic groups. These applications include its uses as purgatives and for the treatment or relief of microbial infections, skin disorders, pains and inflammation. Scientific validation of its diverse uses in traditional medicine has been demonstrated via antimicrobial, anti-inflammatory and toxicity assays. Available results indicate a general poor antimicrobial activity especially with the bulb extracts while the anti-inflammatory activity appears promising. Phytochemical screenings revealed that Bowiea volubilis contains cardiac glycosides and related compounds while reports of other classes of compounds are unavailable. In line with its usage in traditional medicine, the majority of available studies on the species have focused on the use of different solvent extracts from the bulbs. The destructive harvesting of bulbs has led to a continuous decimation of wild populations. Consequently, there are increasing conservational concerns on the sustainability of this species for continuous supply to meet escalating demands. CONCLUSIONS: Bowiea volubilis remains a widely used medicinal plant and available but limited scientific evidence indicates its anti-inflammatory potential. The abundance of cardiac glycosides in its phytochemical composition provides an indication on the therapeutic potential. More research efforts including the application of different biotechnological techniques are still required in order to guarantee its sustainable use over time. PMID- 26277490 TI - Immunohistochemical localization of anterior pituitary cell types of vervet monkey (Chlorocebus aethiops) following sub-chronic cathinone exposure. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Khat (Catha edulis) contains cathinone, an active principal that is customarily used as a psychostimulant that wards off fatigue and to some extent used as an aphrodisiac. AIM OF STUDY: To investigate effects of escalating doses of cathinone on hormone expression by different anterior pituitary cell types using specific antibodies. MATERIAL AND METHODS: Eleven vervet monkeys (6 males and 5 females) divided into tests (n=9) and controls (n=2) were used. Animals were allocated as group I (saline controls), group II (0.8 mg/kg), group III (3.2 mg/kg) and group IV (6.4 mg/kg) of cathinone. All treatments were via oral route at alternate days of each week. At the end of 4 month treatment phase, GnRH agonist (ZOLADEX) was administered to group II (low dose) and group IV (high dose) alongside cathinone for 2 additional weeks. RESULTS: High cathinone dose at long-term exposure caused proliferation of gonadotrophs but decrease in lactotrophs and corticotrophs in anterior pituitary sections of animals while effect of low dose on these cells was insignificant. Subsequent GnRH agonist co-treatment with low and high cathinone doses enhanced gonadotroph proliferation but no change on decline of lactotrophs and corticotrophs. CONCLUSION: We believe that there was a possible potentiation of cathinone on pituitary hormone synthesis thereby influencing reproductive function. Suppression of corticotrophic and lactotrophic functions suggest lowering of stress levels and modulation of reproductive function based on dose level and chronicity of exposure. The findings are consistent with the hypothesis that cathinone interferes with pituitary cell integrity and consequently target organs, but further studies are required to address the precise mechanism underlying this phenomenon. PMID- 26277491 TI - The use of Chinese herbal medicines associated with reduced mortality in chronic hepatitis B patients receiving lamivudine treatment. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Lamivudine associated mutation and resistance reduces the effect of anti-hepatitis B virus. Pharmacological studies in cell and animal model suggest that Chinese herbal medicines (CHMs) have anti-hepatitis B virus effect. Observational studies offer mixed results. The aim of this study was to evaluate the relation between the use of CHMs and outcome in patients with chronic hepatitis B receiving lamivudine treatment and further estimate the association of Jia-Wei-Xiao-Yao-Sang (JWXYS) use with mortality of those patients. MATERIALS AND METHODS: We conducted a cohort study among patients age 20-90 years within a National Health Insurance Healthcare system. Information on the use of CHMs and covariates were obtained from Taiwan National Health Insurance Research Database. We used Cox proportional hazards models to estimate the hazard ratio and 95% confidence intervals (95% CI) for all-cause mortality among CHMs users compared to nonusers. RESULTS: Among 1037 patients studied from 2004 to 2011, median follow-up time 5.3 years and 88 deaths were identified. During the study period, 49% of patients used CHMs and the median duration of use was 2.4 years. We found that significant difference on all-cause mortality among CHMs users (aHR=0.45, 95% CI: 0.27-0.76) compared to CHMs nonusers. All-cause mortality also differed by JWXYS use (aHR=0.26, 95% CI: 0.08-0.83). CONCLUSIONS: This study reveals that the use of CHMs may lower the risk of death in patients with chronic hepatitis B receiving lamivudine treatment. Further randomized controlled trials are required to validate these findings. PMID- 26277493 TI - An overview of the medical management of nonmelanoma skin cancer. AB - Importantly, NMSCs are increasing in prevalence, and full recognition of these diseases as life-threatening entities is paramount. Overall, data supporting adjuvant or systemic therapy in NMSCs are limited, but there are enough reports in the literature to suggest some benefit with systemic agents. Where available, we recommend patients investigate clinical trial options, including phase I studies. Newer targeted therapies and activation of the immune system may provide for a dramatic step forward in the management of these diseases; however, formal clinical trials are necessary to establish these new treatments as a standard of care. PMID- 26277492 TI - Artemisia herba-alba essential oil from Buseirah (South Jordan): Chemical characterization and assessment of safe antifungal and anti-inflammatory doses. AB - ETHNOPHARMACOLOGIC RELEVANCE: Artemisia herba-alba Asso ("desert wormwood" in English; "armoise blanche" in French; "shaih" in Arabic), is a medicinal and strongly aromatic plant widely used in traditional medicine by many cultures since ancient times. It is used to treat inflammatory disorders (colds, coughing, bronchitis, diarrhea), infectious diseases (skin diseases, scabies, syphilis) and others (diabetes, neuralgias). In Jordanian traditional medicine, this plant is used as antiseptic and against skin diseases, scabies, syphilis, fever as well as menstrual and nervous disorders. AIM OF THE STUDY: Considering the traditional medicinal uses and the lack of scientific studies addressing the cellular and molecular players involved in these biological activities, the present study was designed to unveil the antifungal and anti-inflammatory activities of A. herba alba Asso essential oil at doses devoid of toxicity to mammalian cells. MATERIALS AND METHODS: Chemical analysis of A. herba-alba essential oil isolated by hydrodistillation from aerial parts was carried out by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The antifungal activity (minimal inhibitory concentrations and minimal lethal concentrations) was evaluated against yeasts, dermatophyte and Aspergillus strains. In order to explore the mechanisms behind the anti-fungal effect of the essential oil, the germ tube inhibition assay was evaluated using Candida albicans. The assessment of cell viability was accomplished using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay and the in vitro anti-inflammatory potential of A. herba-alba oil at the periphery and central nervous system was evaluated by measuring nitric oxide (NO) production using lipopolysaccharide (LPS)-stimulated mouse macrophages and microglia, respectively. RESULTS: Oxygen containing monoterpenes are the main compounds of the oil, namely 1,8-cineole (20.1%), beta-thujone (25.1%), alpha-thujone (22.9%) and camphor (10.5%). Among the fungal strains tested, the oil demonstrated potential against Trichophyton rubrum and Epidermophyton floccosum, with minimal inhibitory concentration (MIC) and minimal lethal concentration (MCL) values of 0.32 mg/mL and Cryptococcus neoformans with MIC of 0.64 mg/mL. The oil revealed a strong inhibitory effect on germ tube formation in C. albicans with inhibition of filamentation around 90% at a concentration 0.16 mg/mL. Importantly, the essential oil significantly inhibited NO production evoked by LPS without cytotoxicity at concentrations up to 1.25 uL/mL in macrophages and up to 0.32 uL/mL in microglia. Furthermore, evaluation of cell viability in RAW 264.7 macrophages, BW2 microgliacells and HaCaT keratinocytes showed no cytotoxicity at concentrations up to 0.32 MUL/mL. CONCLUSIONS: It was possible to find appropriate doses of A. herba-alba oil with both antifungal and anti-inflammatory activities and without detrimental effects towards several mammalian cell types. These findings add significant information to the pharmacological activity of A. herba-alba essential oil, specifically to its antifungal and anti-inflammatory therapeutic value, thus justifying and reinforcing the use of this plant in traditional medicine. PMID- 26277494 TI - Spinal cord stimulation suppresses atrial fibrillation by inhibiting autonomic remodeling. AB - BACKGROUND: Previous study has shown that spinal cord stimulation (SCS) may suppress atrial fibrillation (AF) inducibility, but the mechanism for this is elusive. OBJECTIVE: The purpose of this study was to determine whether SCS could inhibit AF inducibility by suppressing autonomic remodeling in a canine model of rapid atrial pacing (RAP)-induced AF. METHODS: Eighteen canines were randomly divided into an RAP group (n = 9) and an RAP+SCS group (n = 9). Effective refractory period (ERP), window of vulnerability (WOV), AF inducibility, autonomic neural function, and activity from the anterior right ganglionated plexus (ARGP) and left stellate ganglion (LSG) were measured at baseline, at 3 hours of RAP, and at 6 hours of RAP. Then, ARGP and LSG were excised for Western blot and messenger RNA analysis. In another 4 dogs (control group, which received sham RAP and sham SCS), tissues were also excised for analysis. RESULTS: In the RAP group, RAP resulted in (1) a significant decrease in ERP and an increase in ERP dispersion, SigmaWOV, and AF inducibility and (2) activation of ARGP and LSG versus baseline. In the RAP+SCS group, however, these changes were significantly attenuated by SCS. Compared with the control group, c-fos and nerve growth factor (NGF) were significantly up-regulated and small conductance calcium-activated potassium channel type 2 (SK2) was significantly down-regulated in the RAP group. In the RAP+SCS group, however, c-fos, NGF, and SK2 remained at a normal level compared with the control group. CONCLUSION: SCS may suppress RAP-induced AF by inhibiting autonomic remodeling, and the underlying mechanism of the salutary effect of SCS might contribute to modulation of the expression of c-fos, NGF, and SK2. PMID- 26277495 TI - Role of adipose tissue in the pathogenesis of cardiac arrhythmias. AB - Epicardial adipose tissue is present in normal healthy individuals. It is a unique fat depot that, under physiologic conditions, plays a cardioprotective role. However, excess epicardial adipose tissue has been shown to be associated with prevalence and severity of atrial fibrillation. In arrhythmogenic right ventricular cardiomyopathy and myotonic dystrophy, fibrofatty infiltration of the myocardium is associated with ventricular arrhythmias. In the ovine model of ischemic cardiomyopathy, the presence of intramyocardial adipose or lipomatous metaplasia has been associated with increased propensity to ventricular tachycardia. These observations suggest a role of adipose tissue in the pathogenesis of cardiac arrhythmias. In this article, we review the role of cardiac adipose tissue in various cardiac arrhythmias and discuss the possible pathophysiologic mechanisms. PMID- 26277496 TI - Comparisons of CHADS2 and CHA2DS2-VASc scores for stroke risk stratification in atrial fibrillation: Which scoring system should be used for Asians? AB - BACKGROUND: Both U.S. and European guidelines recommend use of the CHA2DS2-VASc rather than CHADS2 score for stroke risk stratification in atrial fibrillation (AF). However, the CHA2DS2-VASc score has not been proved to be better than CHADS2 score for Asians in a large-scale study. OBJECTIVE: The purpose of this study was to compare the accuracies of CHADS2 and CHA2DS2-VASc scores in predicting ischemic stroke in Chinese patients. METHODS: This study used the National Health Insurance Research Database in Taiwan. A total of 186,570 AF patients without antithrombotic therapies were selected as the study cohort. The clinical end-point was occurrence of ischemic stroke. RESULTS: During follow-up of 3.4 +/- 3.7 years, 23,723 patients (12.7%) experienced ischemic stroke. The CHA2DS2-VASc score performed better than CHADS2 score in predicting ischemic stroke assessed by c-indexes (0.698 vs 0.659, P <.0001). Among 25,286 patients with a CHADS2 score of 0, the CHA2DS2-VASc score ranged from 0 to 3, and the annual stroke rate ranged from 1.15% to 4.47%. Compared to patients with a CHA2DS2-VASc score of 0, the hazard ratio of ischemic stroke for patients with a CHA2DS2-VASc score of 3 was 3.998. CONCLUSION: Patients with a CHADS2 score of 0 were not necessarily "low risk," and the annual stroke rate can be as high as 4.47% when patients were further stratified by the CHA2DS2-VASc score. In contrast, patients with a CHA2DS2-VASc score of 0 had a truly low risk of ischemic stroke, with an annual stroke rate around 1.15%. As with Caucasians, the CHA2DS2-VASc score should be used for stroke risk stratification in Asians. PMID- 26277497 TI - Diagnostic value of tumor blood flow and its histogram analysis obtained with pCASL to differentiate sinonasal malignant lymphoma from squamous cell carcinoma. AB - OBJECTIVES: To investigate the diagnostic value of tumor blood flow (TBF) obtained with pseudo-continuous arterial spin labeling (pCASL) for the differentiation of squamous cell carcinoma (SCC) and malignant lymphoma (ML) in the nasal or sinonasal cavity. METHODS: Thirty-three patients with SCC and 6 patients with ML in the nasal or sinonasal cavity were retrospectively analyzed. Quantitative TBF values were obtained using whole-tumor region of interest (ROI) from pCASL data. The histogram analysis of TBF values within the tumor ROI was also performed by calculating the coefficient of variation (CV), kurtosis, and skewness. The mean TBF value, histogram CV, kurtosis and skewness of the patients with SCC were compared with those of the ML patients. The diagnostic accuracy to differentiate SCC from ML was also calculated by receiver operating characteristic (ROC) curve analysis. In addition, multiple logistic regression models were also performed to determine their independent predictive value, and diagnostic accuracy with the combined use of these parameters. RESULTS: Between the SCC and ML groups, significant differences were observed in mean TBF, CV, and kurtosis, but not in skewness. In ROC curve analysis, the diagnostic accuracy values for the differentiation of SCC from ML in mean TBF, CV, and kurtosis were all 0.87, respectively. Multiple logistic regression models revealed TBF and CV were respectively independent predictive value. With the combination of these parameters, the diagnostic accuracy was elevated to 0.97. CONCLUSIONS: The TBF value and its histogram analysis obtained with pCASL can help differentiate SCC and ML. PMID- 26277498 TI - Coronary CT angiography using low concentrated contrast media injected with high flow rates: Feasible in clinical practice. AB - PURPOSE: Aim of this study was to test the hypothesis that peak injection pressures and image quality using low concentrated contrast media (CM) (240 mg/mL) injected with high flow rates will be comparable to a standard injection protocol (CM: 300 mg/mL) in coronary computed tomographic angiography (CCTA). MATERIAL AND METHODS: One hundred consecutive patients were scanned on a 2nd generation dual-source CT scanner. Group 1 (n=50) received prewarmed Iopromide 240 mg/mL at an injection rate of 9 mL/s, followed by a saline chaser. Group 2 (n=50) received the standard injection protocol: prewarmed Iopromide 300 mg/mL; flow rate: 7.2 mL/s. For both protocols, the iodine delivery rate (IDR, 2.16 gI/s) and the total iodine load (22.5 gI) were kept identical. Injection pressure (psi) was continuously monitored by a data acquisition program. Contrast enhancement was measured in the thoracic aorta and all proximal and distal coronary segments. Subjective and objective image quality was evaluated between both groups. RESULTS: No significant differences in peak injection pressures were found between both CM groups (121 +/- 5.6 psi vs. 120 +/- 5.3 psi, p=0.54). Flow rates of 9 mL/s were safely injected without any complications. No significant differences in contrast-to-noise ratio, signal-to-noise ratio and subjective image quality were found (all p>0.05). No significant differences in attenuation levels were found in the thoracic aorta and all segments of the coronary arteries (all p>0.05). CONCLUSION: Usage of low iodine concentration CM and injection with high flow rates is feasible. High flow rates (9 mL/s) of Iopromide 240 were safely injected without complications and should not be considered a drawback in clinical practice. No significant differences in peak pressure and image quality were found. This creates a doorway towards applicability of a broad variety in flow rates and IDRs and subsequently more individually tailored injection protocols. PMID- 26277499 TI - Homeostasis-based aging model for trabecular changes and its correlation with age matched bone mineral densities and radiographs. AB - PURPOSE: This paper aims (1) to propose a novel bone adaptation model for age related trabecular changes by adopting two implicit parameters in optimization, (2) to compare the simulated bone volume fraction (BV/TV) with the reported bone mineral density (BMD), and (3) to review the simulated trabecular architectures with the age-matched radiographs. MATERIALS AND METHODS: The proposed model simulated the trabecular changes for an age span of 32-80 years. Quantitative comparison was conducted in terms of BMD and other morphometric indices. Then, two radiologists scored the simulated trabecular architectures using the age matched radiographs. This protocol was approved by the hospital institutional review board. RESULTS: The simulated BV/TV was well correlated with BMD reported in the literature (R(2)=0.855; p<0.05). In comparison with age-matched radiographs, the consensus scores of agreement of the trabeculae were higher in age groups over the 50s, and the means of the Ward's triangle areas were strongly correlated with those in the age-matched radiographs (R(2)=0.982; p<0.05). CONCLUSION: The proposed model could reflect the targeted trabecular changes in proximal femur with age. With further follow-up measurements, this research would contribute to the development of patient-specific models that assist radiologists in predicting skeletal integrity with aging. PMID- 26277500 TI - [Lactobacillus rhamnosus GG inhibits Cronobacter-induced meningitis in neonatal rats]. AB - OBJECTIVE: To investigate the inhibitory effect of Lactobacillus rhamnosus GG ( LGG) against Cronobacter-induced meningitis in neonatal rats. METHODS: The cell adhesion and invasion capacities of Cronobacter were assayed in Caco-2 cells, and the optimal time length and concentration of the bacterium for infection were determined. The suppressive effects of LGG on the adhesion and invasion of Cronobacter in caco-2 cells were tested by competitive and exclusion experiments, and its inhibitory effect against Cronobacter-induced meningitis was evaluated in neonatal rats. RESULTS: Cronobacter showed aggressive adhesion to caco-2 cells with an optimal infection time of 3 h. LGG produced a concentration-dependent inhibition of Cronobacter adhesion and invasion by competing with and excluding the latter for cell adhesion. In neonatal rats, LGG showed an obvious preventive effect and also a moderate therapeutic effect against Cronobacter-induced meningitis. CONCLUSION: LGG can inhibit Cronobacter entry across the intestinal barrier to achieve preventive and therapeutic effects against Cronobacter-induced meningitis. PMID- 26277501 TI - [Effect of thalidomide on development of bisphosphonate-related osteonecrosis of the jaws in rats]. AB - OBJECTIVE: To investigate the effect of thalidomide on the development of bisphosphonate-related osteonecrosis of the jaws (BRONJ). METHODS: Thirty-six rats were randomly divided into groups A, B and C, and treated with saline, zoledronate and zoledronate plus thalidomide, respectively. Three weeks later, the left maxillary first molars of the rats were extracted. Four and eight weeks after tooth extraction, samples were harvested for evaluation of osteonecrosis of the jaws, microvessel density, and cell apoptosis. RESULTS: At both of the time points, no exposed dead bone was observed at the extraction socket areas in the rats except for some small fistulas in groups B and C. Histological examination confirmed the absence of dead bone in group A, whereas small areas of dead bone were observed around the extraction socket in groups B and C. Compared with those in group A, the percentage of empty lacunae and the area of dead bone were significantly increased (P<0.01), whereas bone lacunae density was significantly decreased (P<0.01) in groups B and C at both time points. Microvessel density in groups B and C were also significantly decreased (P<0.01) by 25.87% and 55.27% at week 4, and by 45.62% and 72.84% at week 8, respectively; the apoptotic cells in groups B and C increased by 54.80% and 87.89% at week 4 (P<0.01), and by 208.08% and 250.58% at week 8 (P<0.01), respectively. CONCLUSION: Thalidomide can aggravate zoledronate-induced early-stage BRONJ, and their osteonecrosis-inducing effect of the jaw may be attributed, at least partly, to the inhibition of angiogenesis. PMID- 26277502 TI - [Optimization of the protocols for in vitro culture and induction of hepatic differentiation of rat mesenchymal stem cells]. AB - OBJECTIVE: To optimize the protocols for isolation, in vitro culture, identification and induction of hepatic differentiation of rat bone marrow mesenchymal stem cells (BMSCs). METHODS: Rat BMSCs were separated and purified by differential adherent culture for 1.5 h with the first medium change at 12 h. The surface markers of BMSCs were detected by flow cytometry. The cells were induced to differentiate into adipogenic, osteogenic, and chondrogenesis lineages. A 3 step protocol including sequential addition of growth factors, cytokines and hormones was used to induce the BMSCs to differentiate into hepatocyte-like cells. RESULTS: The cells isolated using this protocol were positive for CD29, CD44, and CD90 and negative for CD29 and CD45. The adipogenic, osteogenic, and chondrogenic differentiation of the BMSCs were verified by Oil red, Alizarin red, and toluidine blue staining. The BMSCs induced with the 3-step protocol differentiated into hepatic-like cells that expressed hepatocyte-specific proteins (ALB and AFP) and genes. CONCLUSION: The optimized protocol allows simple and efficient isolation of highly purified populations of BMSCs, which can be induced into hepatic lineages in specific microenvironment. PMID- 26277503 TI - [Clinicopathological characteristics and prognostic factors of intrahepatic biliary cystadenocarcinoma]. AB - OBJECTIVE: To analyze the clinicopathological characteristics and the factors affecting the prognosis of intrahepatic biliary cystadenocarcinoma (IBC). METHODS: Forty-six patients with histologically confirmed IBC from January, 2000 to April, 2014 were included. The clinical characteristics of the patients with IBC were compared with those of 58 patients with intrahepatic biliary cystadenoma (IBCA). Kaplan-Meier analysis was used to identify the factors affecting the prognosis of IBC. RESULTS: The 46 patients with IBC included 15 men and 31 women with a mean age of 57.0 +/- 10.5 years. Compared with the patients with IBCA, IBC patients had an older mean age (57.0 +/- 10.7 vs 44.3 +/- 15.3 years, P=0.03) and a greater proportion of male patients (15/46 vs 8/58, P=0.02). The differential diagnosis between IBC and IBCA was difficult on the basis of preoperative laboratory and imaging findings. The median overall survival of IBC patients was 56 months with 1-, 3-, and 5-year survival rates of 85.9%, 65.2%, and 47.7%, respectively. Gender, surgical approach, tumor growth pattern and distant metastasis were all significant prognostic factors for the overall survival of the patients. CONCLUSION: IBC is a rare cystic lesion occurring primarily in middle-aged men. Complete resection is recommended for curative treatment and close follow-up is essential especially for male patients and patients with tumors exhibiting an invasive growth. PMID- 26277504 TI - [Effects of Panax notoginseng saponins on proliferation, apoptosis and cell cycle of K562 cells in vitro and the mechanisms]. AB - OBJECTIVE: To investigate the effects of Panax notoginseng saponins (PNS) on the proliferation, apoptosis and cell cycle of K562 cells and explore the molecular mechanisms underlying these effects. METHODS: PNS-induced growth inhibition of K562 cells was detected by MTT assay; the cell apoptosis was evaluated by AO/EB staining and Annexin V-FITC/ PI staining; flow cytometry was used to detect cell cycle changes in the treated cells. The mRNA expressions of the molecules in mTOR signaling pathway were examined by RT-PCR, and the cellular expressions of cleaved caspeas-3, cyclin D1 and major proteins in mTOR signaling pathway were detected using Western blotting. RESULTS: MTT assay showed that treatment with 100-800 ug/mL PNS significantly inhibited the proliferation, promoted the cell apoptosis, and caused cell cycle arrest in G0/G1 phase in K562 cells. Western blotting revealed increased protein expression of cleaved caspase-3 and decreased expression of cyclin D1 in PNS-treated cells, in which the proteins expressions of mTOR, p-mTOR, p-p70S6K and p-4E-BP 1 and the mRNA expression of mTOR were all decreased. CONCLUSION: PNS can inhibit the proliferation, induce apoptosis and cause cell cycle arrest in K562 cells possibly by up-regulating cleaved caspase 3 and down-regulating cyclin D1 and mTOR signaling pathway. PMID- 26277505 TI - [Proanthocyanidins inhibit pancreatic cancer AsPC-1 cell growth and migration through up-regulation of let-7a]. AB - OBJECTIVE: To ascertain whether proanthocyanidins inhibit cell growth and migration by increasing let-7a expression in pancreatic cancer AsPC-1 cells. METHODS: The proliferation rate, cell apoptosis rate and cell migration ability of AsPC-1 cells treated with proanthocyanidins were measured by MTT assay, Annexin V-FITC/PI staining, and Transwell migration assay, respectively. The expression of let-7a AsPC cells was detected by miRNA real-time RT-PCR after proanthocyanidins treatment. The changes in the biological behaviors of AsPC-1 cells were evaluated after transfection with let-7a mimics. RESULTS: Compared with the control group, proanthocyanidins treatment caused dose-dependent decrements of the proliferation rate and migration ability and increased the apoptosis rate in AsPC-1 cells. AsPC-1 cells with proanthocyanidins treatment showed increased expression of let-7a. Transfection with let-7a mimics resulted in obvious decreases in the cell growth rate and migration ability, and proanthocyanidins treatment significantly enhanced the inhibitory effect of let 7a mimics. CONCLUSION: Proanthocyanidins-induced cell growth and migration inhibition are partially mediated by up-regulation of let-7a expression in AsPC-1 cells. PMID- 26277506 TI - [Automatic extraction of the pennation angle of the gastrocnemius muscles from ultrasound radiofrequency signals]. AB - OBJECTIVE: We propose a cross-correlation method for automatic extraction of the pennation angle (PA) of the gastrocnemius (GM) muscle from ultrasound radiofrequency (RF) signals. METHODS: The ultrasound RF signals of the GM muscles in tension condition from normal subjects and the simulated ultrasound signals were collected. After the starting point of tracking, a fascicle was selected in the reconstructed GM ultrasound image from the RF signals, and the fascicle and deep aponeurosis could be automatically tracked using the cross-correlation algorithm. The lines of the fascicle and deep aponeurosis were then drawn and the PA was calculated. The reproducibility of the proposed method and its consistency with the manual measurement method were tested. RESULTS: The angles of the simulated fascicles were precisely extracted automatically. The difference between the experimental measurement and the theoretical values was less than 1 degrees . The PA measured automatically and manually was 20.48 degrees ?0.47 degrees and 21.49 degrees ?1.79 degrees , respectively. The coefficient of variation (CV) of the two methods was less than 3% and the root-mean square error (RMSE) was less than 1 degrees . Bland-Altman plot showed a good agreement between the proposed automatic method and the manual method. CONCLUSION: The proposed cross-correlation automatic measurement method can detect the orientation of the fascicle and deep aponeurosis and measure the PA based on ultrasound RF signals with serious speckle noise. PMID- 26277507 TI - [Establishment of a colorectal cancer SW620 cell line stably over-expressing Wilm's tumor on X chromosome using a recombinant lentivirus vector]. AB - OBJECTIVE: To construct a recombinant lentivirus vector for Wilm's tumor on X chromosome (WTX) gene and establish a colorectal cancer SW620 cell line with stable WTX over-expression. METHODS: The full length coding region of WTX gene was amplified with PCR, and the amplified fragment was cloned into the lentivirus vector GV387. The recombinant lentivirus vector was transfected in 293T cells for packaging the virus, which was then transfected into colorectal cancer SW620 cells. The stably transfected cells were selected with G418, and the cellular expressions of WTX mRNA and protein were detected using quantitative PCR and Western blotting. RESULTS: The recombinant plasmid was successfully constructed as verified by sequence analysis. Quantitative PCR and Western blotting results showed that trasnfection with the recombinant lentivirus significantly increased the expression levels of WTX in SW620 cells. CONCLUSION: We successfully established a colorectal cancer cell lines with stable over-expression of WTX, which provides an essential cell model for studying the role of WTX in the tumorigenesis and progression of colorectal cancer. PMID- 26277508 TI - [Effects of allitridum on rapidly delayed rectifier potassium current in HEK293 cell line]. AB - OBJECTIVE: To study the effect of allitridum on rapidly delayed rectifier potassium current (IKr) in HEK293 cell line. METHODS: HEK293 cells were transiently transfected with HERG channel cDNA plasmid pcDNA3.1 via Lipofectamine. Allitridum was added to the extracellular solution by partial perfusion after giga seal at the final concentration of 30 umol/L. Whole-cell patch clamp technique was used to record the HERG currents and gating kinetics before and after allitridum exposure at room temperature. RESULTS: The amplitude and density of IHERG were both suppressed by allitridum in a voltage-dependent manner. In the presence of allitridum, the peak current of IHERG was reduced from 73.5?4.3 pA/pF to 42.1?3.6 pA/pF at the test potential of +50 mV (P<0.01). Allitridum also concentration-dependently decreased the density of the IHERG. The IC50 of allitridum was 34.74 umol/L with a Hill coefficient of 1.01. Allitridum at 30 umol/L caused a significant positive shift of the steady-state activation curve of IHERG and a markedly negative shift of the steady-state inactivation of IHERG, and significantly shortened the slow time constants of IHERG deactivation. CONCLUSION: Allitridum can potently block IHERG in HEK293 cells, which might be the electrophysiological basis for its anti-arrhythmic action. PMID- 26277509 TI - [Role of calmodulin-dependent protein kinase II in bupivacaine hydrochloride induced injury of SH-SY5Y cells]. AB - OBJECTIVE: To investigate the effect of KN93, a calmodulin-dependent protein kinase II (CaMK II) inhibitor, on SH-SY5Y cell injury induced by bupivacaine hydrochloride. METHODS: SH-SY5Y cells exposed for 24 h to 1 mmol/L KN93, 1 mmol/L bupivacaine hydrochloride, or both were examined for morphological changes and Cav3.1 protein expressions using Western blotting. The vitality and apoptosis rate of the cells at different time points during the exposures were assessed with MTT assay and flow cytometry, respectively. RESULTS: Bupivacaine hydrochloride exposure caused obvious cell morphologial changes, reduced cell viability, increased cell apoptosis, and enhanced Cav3.1 protein expression. All these changes were partly reversed by treatment of the cells with 1 mmol/L KN93. CONCLUSIONS: CaMKII may play a role in bupivacaine hydrochloride-induced SH-SY5Y cells injury, which is related with upregulated Cav3.1 protein expression. PMID- 26277510 TI - [Preparation and identification of rabbit polyclonal antibodies against vacuolar proton pyrophosphatase type I of Toxoplasma gondii]. AB - OBJECTIVE: To prepare and characterize rabbit polyclonal antibodies against Toxoplasma gondii vacuolar proton pyrophosphatase type I (TgVP1). METHODS AND RESULTS: Two synthesized peptides TgVP1-1 and TgVP1-2 as the haptens were conjugated with KLH to immunize rabbits. Indirect ELISA showed that the titers of rabbit anti-TgVP1-1 polyclonal antibody and rabbit anti-TgVP1-2 polyclonal antibody reached 1:128 000. Western blotting results revealed that both purified polyclonal antibodies could specifically bind to a purified 85 kD T. gondii protein predicted as TgVP1. The protein detected by these two polyclonal antibodies was distributed in the cytoplasm of T. gondii tachyzoite, and this distribution pattern was consistent with that of acidocalcisome. CONCLUSION: The peptide-based method of antibody generation is efficient and the obtained TgVP1 polyclonal antibodies possess a high specificity to facilitate further study of T. gondii acidocalcisome and the diagnosis of toxoplasmosis. PMID- 26277511 TI - [Brain image segmentation based on multi-weighted probabilistic atlas]. AB - OBJECTIVE: We propose a multi-weighted probabilistic atlas to obtain accurate, robust, and reliable segmentation. The local similarity measure is used as the weight to compute the probabilistic atlas, and the distance field is used as the weight to incorporate the locality information of the atlas; the self-similarity is used as the weight to incorporate the local information of target image to refine the probabilistic atlas. Experimental results with brain MRI images showed that the proposed algorithm outperforms the common brain image segmentation methods and achieved a median Dice coefficient of 87.1% on the left hippocampus and 87.6% on the right. PMID- 26277512 TI - [Effect of cancer-associated fibroblasts on proliferation and invasion of gallbladder carcinoma cells]. AB - OBJECTIVE: To investigate the effect of cancer-associated fibroblasts (CAFs) on the growth and invasion of gallbladder cancer cells. METHODS: The CAFs were isolated from human primary gallbladder carcinoma tissues by tissue culture and digestion methods. The cells were purified by differential adhesion method, and the primary cells were identified morphologically and immunocytochemically. The proliferation and invasion of two human gallbladder carcinoma cell lines (SBC-996 and GBC-SD) co-cultured with CAFs were detected by MTT and Transwell chamber assays. RESULTS: Gallbladder carcinoma CAFs were isolated successfully by both tissue culture and enzyme digestion methods, and the latter method was more convenient and efficient. MTT and Transwell assays showed that CAFs significantly promoted the proliferation and invasion of the two gallbladder carcinoma cell lines. CONCLUSION: CAFs can promote the proliferation and invasion of gallbladder carcinoma cells in vitro, suggesting the important role of CAFs in the development of gallbladder carcinoma. PMID- 26277513 TI - [Minocycline reduces hyperpolarization-activated current in rat substantia gelatinosa neurons]. AB - OBJECTIVE: To investigate the effect of minocycline on hyperpolarization activated current (Ih) in the substantia gelatinosa (SG) neurons in rat spinal dorsal horn. METHODS: In vitro spinal cord transverse slices were prepared from 3 5-week-old male Sprague-Dawley rats. Using whole-cell patch clamp technique, Ih currents were recorded before and after bath application of minocycline (1-300 umol/L) to the SG neurons. RESULTS: Ih currents were observed in nearly 50% of the recorded neurons, and were blocked by Ih blocker CsCl and ZD7288. Minocycline rapidly and reversibly reduced the amplitude of Ih and decreased the current density in a concentration-dependent manner with an IC50 of 34 umol/L. CONCLUSION: Minocycline suppresses the excitability of SG neurons through inhibiting the amplitude and current density of Ih and thereby contributes to pain modulation. PMID- 26277514 TI - [Effect of sulindac on improving autistic behaviors in rats]. AB - OBJECTIVE: To test the effect of sulindac on autistic behaviors in a rat model and explore the possible mechanisms. METHODS: Autistic rat models were established by a single intraperitoneal injection of sodium valproate (VPA) at 12.5 days of pregnancy. The pregnant rats were treated with oral sulindac at a daily dose of 80 mg/kg until weaning of the newborn rats (23 days after being born), which were divided into control, VPA treatment, sulindac treatment, and VPA+ sulindac treatment groups. The social interaction and neuroethology of the newborn rats were evaluated at 35 days, and the levels of beta-catenin and phosphorylated Gsk3beta in the brain tissues were investigated by Western blotting. RESULTS: Compared with the control rats, the rats treated with VPA showed lower social interaction, longer moving time in central area, and reduced standing times. Treatment with sulindac alone resulted in no obvious changes in the social interaction or neuroethology of the newborn rats, but sulindac treatment corrected VPA-induced autistic-like behaviors. Sulindac also attenuated VPA-triggered p-Gsk3beta downregulation and beta-catenin upregulation in the prefrontal lobe, seahorse and cerebellum. CONCLUSION: Sulindac can improve the behaviors of autistic rats possibly by suppressing Wnt signaling pathway. PMID- 26277515 TI - [Short-term follow-up results of hybrid coronary revascularization by robotic coronary artery bypass grafting and stent implantation]. AB - OBJECTIVE: To assess the short-term outcomes of staged hybrid coronary revascularization performed using robotic-assisted off-pump coronary bypass grafting followed by percutaneous coronary intervention (PCI) in a non-left anterior descending (LAD) coronary artery lesion. METHODS: From January, 2007 to May, 2013, 35 patients (32 male and 3 female patients, mean age 56.7 +/- 9.6 years) underwent staged hybrid coronary revascularization. Ten patients had double-vessel and 25 patients had triple-vessel coronary diseases, and the lesions involved an average of 2.7 +/- 0.5 coronary vessels. Coronary artery bypass grafting was completed in robotic-assisted left internal thoracic artery (ITA) harvesting and LITA to LAD bypass. Coronary angiography or 64-MSCT was performed to evaluate the patency of the ITA and stents at 6 months and at 1 to 5 years postoperatively. The patients were followed for major adverse cardiac events (MACE) including cardiac death, acute myocardial infarction and target lesion revascularization. RESULTS: Staged hybrid revascularization was completed successfully in all the patients without complications. The LITA to LAD anastomosis was completed in minimally invasive direct coronary bypass grafting (MIDCAB) or totally robotic coronary bypass grafting on beating heart (TECAB) with the assistance of da Vinci Surgical System. The mean artery graft flow was 36.0 +/- 22.5 ml/min, and the graft had a 100% patency before discharge. A total of 49 stents were deployed in 35 patients within 2 weeks after robotic coronary bypass grafting, with a mean of 1.34 +/- 0.6 stents per case (1 stent in 23 cases, 2 stents in 11 cases, and 3 stents in 1 case). The patients were followed up for 17.5 +/- 11.6 months, and 1 patient had artery graft occlusion and another had in-stent occlusion at 6 months. All the other 33 patients had patent LITA-to LAD anastomosis without angina or MACE. CONCLUSION: Staged hybrid revascularization strategy has acceptable angiographic patency results for both LITA-LAD grafts and PCI interventions. PMID- 26277516 TI - [Shenshuai Yingyang capsule ameliorates muscle atrophy in rats with chronic renal failure: role of Wnt7a-Akt/mTOR signal pathway]. AB - OBJECTIVE: To observe the effect of Shenshuai Yingyang Capsule (SSYYJN) in ameliorating muscle atrophy in rats with chronic renal failure (CRF) and explore the role of Wnt7a-Akt/mTOR signal pathway in mediating this effect. METHODS: Male rats were randomly assigned to 5/6 nephrectomy group and sham-operated group, and the former group was further randomly divided into CRF model group, KA group, and SSYYJN group. The size of anterior tibia muscle was examined microscopically with HE staining. Protein synthesis in the soleus muscle was investigated by (14)C phenylalanine experiment, and the expression of Wnt7a, frizzled-7, phospho-Akt, phospho-mTOR and GAPDH were detected with Western blotting. RESULTS: The body weight, the wet and dry weight, cross-sectional area, and muscle protein synthesis of the anterior tibia muscles, and expressions of the proteins in the Wnt7a/Akt signaling pathway all increased significantly in SSYYJN and KA groups as compared with those in the model group. CONCLUSION: SSYYJN can effectively improve muscle atrophy in the rat model of CRF possibly by reversing the reduction in the expressions of Wnt7a/Akt signaling pathway proteins in the skeletal muscles. PMID- 26277517 TI - [Radioimmunoimaging of lymphoma in mice with a two-step pretargeting strategy using biotinyled CD45 monoclonal antibody and (188)Re-avidin]. AB - OBJECTIVE: To establish a two-step pretargeting approach to lymphoma radioimmunoimaging in mice using biotinynaled CD45 monoclonal antibody (McAb) and (188)Re-avidin in a tumor-bearing mouse model. METHODS: Six Nod-Scid mice bearing lymphoma cell xenograft were randomized to receive either an intravenous injection of 50 ug/200 uL biotinyled CD45 McAb followed 24 h later by an intraperitoneal injection of 3.7 MBq (50 ug/100 uL) (188)Re-avidin (two-step pretargeting group), or a single intravenous injection of 3.7 MBq (100 ug/100 uL) (188)Re-CD45 McAb (control group). SPECT was performed at 0.5, 1, 6 and 23 h post injection to characterize (188)Re isotope biodistribution. At 24 h pos-injection, the mice were sacrificed for measurement of radioactivity uptake in the tumor and normal tissues and calculation of the tumor-to-non-tumor (T/NT) ratios. RESULTS: SPECT showed that the two-step pretargeting method resulted in a low radioactivity in the blood pool during the imaging and a concentrated radioactivity in the liver and spleen. The transplanted tumor began to be displayed at 1 h post-injection and was clearly displayed at 1-6 h; the images were clear even at 23 h. With the two-step pretargeting method, the radioactive uptake at 24 h post-injection were (1.34?0.52)%, (6.77?2.32)%, and (2.81?1.25)% in the tumor, kidney and liver, respectively, with low radioactivity levels in other organs and high tumor/blood and tumor/muscle ratios (4.28?0.82 and 8.00?0.88, respectively). In the control group, SPECT revealed intense radioactivity in the liver, spleen, and kidneys with obscure display of the tumor; at 20 h, the radioactivity in the blood pool remained high but that in the tumor was low, and the tumor/blood and tumor/muscle ratios at 24 h were only 0.58?0.06 and 3.21?0.24, respectively. CONCLUSION: Compared with (188)Re-CD45 McAb, the two-step pretargeting approach exhibits a good specificity in targeting lymphoma with an increased T/NT ratio in mice and allows early tumor display at 1 h post-injection. PMID- 26277518 TI - [Structural changes in the gray matter in patients with trigeminal neuralgia: a voxel-based morphometric study]. AB - OBJECTIVE: To investigate the changes in whole brain gray matter volume in patients with trigeminal neuralgia using voxel-based morphometry (VBM). METHODS: Twenty-eight patients with trigeminal neuralgia and 28 healthy controls underwent magnetic resonance imaging with a Philips 1.5T MRI scanner. VBM was used to compare the structural differences in the whole brain gray matter between the two groups based on the DARTEL after data preprocessing with SPM8 software package. RESULTS: Compared with the healthy controls, the patients with trigeminal neuralgia presented with decreased gray matter volume in several brain regions including the bilateral middle temporal gyrus, bilateral superior/middle frontal gyrus, left pre-/post-central gyrus, right fusiform and anterior cingulate gyrus. CONCLUSIONS: Patients with trigeminal neuralgia had abnormal gray matter volume in some brain regions associated with perception and processing of pain sensation. These changes may provide clues for further exploration of the neuropathogenic basis of trigeminal neuralgia. PMID- 26277519 TI - [Soft tissue regeneration after implantation of two novel citric acid-based biodegradable materials in rats]. AB - OBJECTIVE: To observe the soft tissue regeneration after implantation of two novel citric acid-based biodegradable materials in the skull defects in rats. METHODS: Two novel citric acid-based biodegradable materials were implanted in the muscular tissues in the thigh and harvested 2 weeks later. Another 40 rats with surgically induced cranial defect were randomized into control group, autograft group, CUPE-HA group, and POC-HA group (n=10), and 3 months after implantation, the materials were harvested for histological and morphometric analyses. RESULTS: Soft tissue regeneration was stimulated by the two biodegradable materials in the muscular tissues. The implants also stimulated angiogenesis and soft tissue regeneration in the cranial defect and accelerated of intramembranous ossification. CONCLUSION: The 2 novel citric acid-based biodegradable materials can induce angiogenesis and soft tissue regeneration and accelerate intramembranous ossification in rats with cranial defects. PMID- 26277520 TI - [Mechanism of continuous venovenous hemofiltration combined with ulinastatin for the treatment of septic shock]. AB - OBJECTIVE: To investigate the molecular mechanisms of continuous venovenous hemofiltration (CVVH) combined with ulinastatin (ULI) (CVVH-ULI) for the treatment of septic shock. METHODS: Human umbilical endothelial cells (HUVECs) were incubated with serums isolated from normal healthy people (control), septic shock patients treated with conventional therapy (CT) or treated with CVVH combined with ULI (CVVH-ULI). Endothelial permeability was evaluated by the leakage of FITC-labeled albumin. The morphological changes of F-actin was evaluated by Rhodamine-phalloidin. The phosphorylated levels of p38 were determined by Western blot. Cells were then treated with p38inhibitor (SB203580), or DMSO, followed by incubation with serum from septic shock patients treated with conventional therapy. Endothelial permeability and F-actin rearrangements were also evaluated as noted above. RESULTS: Serum from CT group increased endothelial permeability, F-actin rearrangements, and phosphorylated levels of p38, which were inhibited by CVVH-ULI treatment. Moreover, in CT group, the serum induced endothelial hyperpermeability and F-actin rearrangements were inhibited by SB203580, the inhibitor of p38. CONCLUSION: CVVH combined with ulinastatin decreases endothelial hyperpermeability induced by septic shock through inhibiting p38 MAPK pathways. PMID- 26277521 TI - [Bilateral ultrasound-guided supraclavicular brachial plexus block in shoulder joint release surgery for shoulder periarthritis]. AB - OBJECTIVE: To observe the anesthetic efficacy and safety of bilateral ultrasound guided supraclavicular brachial plexus block in patients undergoing arthrolysis for shoulder periarthritis. METHODS: Twenty-seven patients (ASA class I-II) undergoing bilateral shoulder joint release surgery and 24 ml received bilateral ultrasound-guided supraclavicular brachial plexus block anesthesia with 0.4% ropivacaine and 0.8% lidocaine. The visual analogue scale (VAS) scores for shoulder joint pain were recorded before and after anesthesia. The efficacy of axillary nerve, dorsal scapular nerve and suprascapular nerve block was evaluated, and the anesthetic effect and complications was assessed during surgery. Before and after anesthesia, the range of left and right diaphragmatic muscle movement was measured when the patient took a quiet breath and a deep breath. RESULTS: The patients showed no significant variations in MAP, HR, or SpO2after anesthesia. The VAS scores of shoulder joint pain during anteflexion, abduction, posterior extension, rotation, posterior extension and medial rotation were significantly lowered after anesthesia (P<0.05), but the left and the right diaphragm movement range showed no significant difference between quiet breath and deep breath (P>0.05). The rates of complete block of the axillary nerve and dorsal scapular nerve was 100%, and that of suprascapular nerve was 92.6%. Partial phrenic nerve block occurred in 1 case with mild local anesthetic toxicity in another. CONCLUSIONS: Bilateral ultrasound-guided supraclavicular brachial plexus block in patients has excellent analgesic effect in should joint release surgery with good safely. PMID- 26277522 TI - [Spd1672 gene knockout significantly attenuates the virulence of Streptococcus pneumoniae]. AB - OBJECTIVE: To investigate the role of spd1672 gene in the infection process of Streptococcus pneumoniae. METHODS: BALB/c mice were intraperitoneally infected by a spd1672 knockout strain and a D39 wild-type strain of S. pneumoniae, and the survival time of mice and blood bacterial counts were recorded. The adhesion and invasion ability of S. pneumoniae strains were assessed in A549 cells. Bactericidal assays were carried out to determine the resistance of spd1672 knockout strains and D39 wild strains, and the serum levels of inflammatory cytokines were detected in the infected mice. RESULTS: The mice infected with spd1672 knockout strains showed a significantly longer median survival time, a higher survival rate, and a lower blood bacterial load than the wild strain infected mice (P<0.05). Having a similar cell adhesion ability to the wild-type strain (P>0.05), the spd1672 knockout strain showed significantly lower cell invasion ability than the wild-type strain (P<0.05). The spd1672 knockout strain also had a reduced resistance to whole blood cells, and thw mice infected with spd1672 knockout strain exhibit lower levels of serum inflammatory cytokines than those infected with the wild-type strain. CONCLUSION: Spd1672 gene is importantly related to the virulence of S. pneumoniae and plays important roles in modulating bacterial invasion, resistance to whole blood cells and proinflammatory responses. PMID- 26277523 TI - [Immunoexpression of apollon in breast cancer tissues before neoadjuvant chemotherapy and its clinical significance]. AB - OBJECTIVE: To investigate whether apollon immunoexpression in breast cancer tissues helps to predict pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). METHODS: The expressions of Apollon, Her-2, estrogen receptor (ER) and progesterone receptor (PR) were detected immunohistochemically in biopsy tissues from 124 breast cancer patients. The clinical responses to NAC were evaluated in line with the response evaluation criteria in solid tumors (RECIST). The pCR rate was analyzed for different types of breast cancer. The correlations between Apollon status with Her-2, ER, PR, lymph node status and tumor size were analyzed. Immunohistochemistry was used to compared the changes in Apollon expression in the breast cancer tissues before and after NAC. RESULTS: The pCR rate was 18.5% (23/124) in these patients. Negative expressions of apollon, ER and PR were all associated with a higher pCR rate after NAC. Apollon was significantly correlated with Her-2, ER, PR and lymph node involvement. Chemotherapy significantly down-regulated apollon expression in the tumor cells. CONCLUSION: A negative apollon expression might be a predictor of pCR in patients with breast cancer. PMID- 26277524 TI - [Hyperbaric oxygen therapy at different pressure levels for aphasia following craniocerebral injury: efficacy, safety and patient adherence to therapy]. AB - OBJECTIVE: To observe the clinical effect of hyperbaric oxygen (HBO) therapy at different pressure levels on aphasia after craniocerebral injury and assess the patient adherence to the therapies. METHODS: Thirty-one patients with aphasia after craniocerebral injury receiving 30 sessions of HBO therapy at the pressure level of 0.175 MPa and another 31 patients receiving 0.2 MPa therapy were recruited as the treatment groups 1 and 2, respectively; 31 patients who refused to have HBO therapy served as the control group. All the patients received routine therapy. The therapeutic effects were assessed using Western Aphasia Battery (WAB) before and after the therapy. The WAB item and AQ scores, curative effect, and recovery time of aphasia were compared between the 3 groups. RESULTS: The total response rate was significantly lower in the control group as compared with those in treatment groups 1 and 2 (58.06% vs 83.87% and 87.1%). WAB item scores and AQ scores, curative effect, and recovery time of aphasia all showed significant differences between the control group and the two treatment groups (P<0.05), but not between the latter 2 groups (P>0.05). Compared with 0.20 MPa HBO therapy, 0.175 MPa HBO therapy showed a better patient adherence with a significantly lowered non-adherence rate (by 31.37%) an increased partial and total adherence rates (by 13.86% and 17.51%, respectively). CONCLUSION: HBO therapy at the pressure level of 0.175 MPa is more appropriate for treatment of aphasia after craniocerebral injury to ensure the safety, efficacy and patient compliance. PMID- 26277525 TI - [Effects of anti-survivin oligonucleotides on growth of peritoneally implanted ovarian cancer xenografts in nude mice]. AB - OBJECTIVE: To observe the effect of anti-survivin oligonucleotides (ASODN) on the invasion and growth of peritoneally implanted ovarian cancer cell xenografts in nude mice. METHODS: Nude mouse models bearing peritoneally implanted ovarian cancer cell (SKOV3) xenografts were established and subjected to intraperitoneal injection of survivin ASODN or saline (control). The number and weight of the intraperitoneal xenografts were compared between the two groups.The expressions of interleukin (IL-6), signal transducer and activator of transcription3 (STAT3), phosphorylated STAT3 (p-STAT3), and survivin protein in the tumor tissues were detected with Western blotting in both groups. RESULTS: Compared with those in the control group, the number and weight of the intraperitoneal xenografts were significantly reduced in ASODN group (P<0.05). ASODN treatment also resulted in significantly lowered protein levels of IL-6, STAT3, p-STAT3, and survivin in the tumor tissues (P<0.05). CONCLUSION: Survivin ASODN can suppress the invasion and migration capacity of ovarian cancer cells and inhibit peritoneal metastasis of the tumor in nude mice possibly though down-regulation of IL-6/STAT3 signaling pathway. PMID- 26277526 TI - [Value of specific 16S rDNA fragment of algae in diagnosis of drowning: an experiment with rabbits]. AB - OBJECTIVE: To establish a method for amplifying specific 16S rDNA fragment of algae related with drowning and test its value in drowning diagnosis. METHODS: Thirty-five rabbits were randomly divided into 3 the drowning group (n=15), postmortem water immersion group (n=15, subjected to air embolism before seawater immersion), and control group(n=5, with air embolism only). Twenty samples of the liver tissues from human corpses found in water were also used, including 14 diatom-positive and 6 diatom-negative samples identified by microwave digestion vacuum filtration-automated scanning electron microscopy (MD-VF-Auto SEM). Seven known species of algae served as the control algae (Melosira sp, Nitzschia sp, Synedra sp, Navicula sp, Microcystis sp, Cyclotella meneghiniana, and Chlorella sp). The total DNA was extracted from the tissues and algae to amplify the specific fragment of algae followed by 8% polyacrylamide gelelectrophoresis and sliver-staining. RESULTS: In the drowning group, algae was detected in the lungs (100%), liver (86%), and kidney (86%); algae was detected in the lungs in 2 rabbits in the postmortem group (13%) and none in the control group. The positivity rates of algae were significantly higher in the drowning group than in the postmortem group (P<0.05). Of the 20 tissue samples from human corps found in water, 15 were found positive for algae, including sample that had been identified as diatom-negative by MD-VF-Auto SEM. All the 7 control algae samples yielded positive results in PCR. CONCLUSIONS: The PCR-based method has a high sensitivity in algae detection for drowning diagnosis and allows simultaneous detection of multiple algae species related with drowning. PMID- 26277527 TI - Changes in weight, length, head circumference, and ponderal index at birth of healthy term newborns in nine cities in China during the period of rapid social development 1985-2005. AB - The changes in the anthropometric parameters at birth of healthy singleton term newborns in nine cities in China were analyzed by means of the data collected in three large-scale cross-sectional physical growth surveys in 1985, 1995, and 2005 (n=6660, 7109 and 6144). Between 1985 and 2005, average increases in body weight (BW), body length (BL), ponderal index (PI), and head circumference (HC) of newborns were statistically significant: 107g, 0.2cm, 0.6kg/m(3) and 0.4cm, respectively. The relative increase in BW was more than that in BL (3.4% vs 0.4%) in the last two decades, leading to an increase in PI. The distribution of birth size shifted slightly to the right, and the proportion of macrosomia increased from 3.2% in 1985 to 3.4% in 1995 and to 4.3% in 2005. The increases in BW and PI and the increase in rate of macrosomia are concerns from public health perspectives. PMID- 26277528 TI - Disentangling the link between depressive symptoms and plasma oxytocin in men: The role of brooding rumination. AB - The links between plasma oxytocin and depression are controversial, ranging from negative to positive associations. The present study was conducted to reconcile those conflicting findings; amongst the features of depression, we considered rumination and hypothesised that rumination would function as moderator between depressive symptoms and oxytocin. Seventy five clinically normal adult male volunteers were assessed for depressive characteristics by means of the Ruminative Responses Scale and Beck's Depression Inventory-II; plasma oxytocin was measured by means of competitive enzyme immunoassay. The results demonstrate that high depressive symptoms were negatively associated with oxytocin concentrations at high rumination levels while such an association did not exist at low levels of rumination. The present findings suggest there are complex associations between oxytocin and brooding rumination, the latter being an important feature among depressive symptoms observed in clinically normal individuals. This complexity can underlie the current lack of consensus on the role of oxytocin in depression. PMID- 26277530 TI - Hepatectomy for liver metastases in non-colorectal, non-neuroendocrine cancer patients. The survival benefit in primary unresectable cases. AB - BACKGROUND: Although liver resection is widely accepted as a potentially curative treatment for colorectal liver metastases, there is an ongoing debate on the indications for hepatectomy for the treatment of liver metastases from non colorectal primary tumors. The number of candidates for hepatectomy for non colorectal liver metastases may increase due to advances in chemotherapy; however, the factors related to prognosis after hepatectomy for non-colorectal liver metastases have yet to be clearly elucidated. METHODS: The clinical outcomes of 59 patients who underwent hepatectomy for non-colorectal liver metastases at a single institute were retrospectively analyzed. RESULTS: The 5 year overall survival rate after hepatectomy for non-colorectal, non neuroendocrine liver metastases was 30%, and 8 patients (gastric cancer (n = 2), ovarian cancer (n = 2), uterine cancer (n = 2) and breast cancer (n = 2)) survived for 5 years. The 5-year disease-free survival rate after hepatectomy was 28%. The postoperative morbidity rate was 25%; however, there were no cases of in hospital mortality and no patients suffered liver failure. The presence of bilateral liver metastases was identified to be an independent predicting factor for poor prognosis by a multivariate analysis (P = 0.049). The survival rate of the conversion cases (initially unresectable and converted to resection after chemotherapy) was not inferior to that of primary resectable cases in terms of either overall survival or disease-free survival. CONCLUSION: The present study demonstrates that hepatectomy for liver metastases from non-colorectal tumors is safe and that it may be a promising strategy for prolonging survival and achieving a cure. PMID- 26277529 TI - Glutamatergic and GABAergic susceptibility loci for heroin and cocaine addiction in subjects of African and European ancestry. AB - BACKGROUND: Drug addiction, a leading health problem, is a chronic brain disease with a significant genetic component. Animal models and clinical studies established the involvement of glutamate and GABA neurotransmission in drug addiction. This study was designed to assess if 258 variants in 27 genes of these systems contribute to the vulnerability to develop drug addiction. METHODS: Four independent analyses were conducted in a sample of 1860 subjects divided according to drug of abuse (heroin or cocaine) and ancestry (African and European). RESULTS: A total of 11 SNPs in eight genes showed nominally significant associations (P<0.01) with heroin and/or cocaine addiction in one or both ancestral groups but the associations did not survive correction for multiple testing. Of these SNPs, the GAD1 upstream SNP rs1978340 is potentially functional as it was shown to affect GABA concentrations in the cingulate cortex. In addition, SNPs GABRB3 rs7165224; DBI rs12613135; GAD1 SNPs rs2058725, rs1978340, rs2241164; and GRIN2A rs1650420 were previously reported in associations with drug addiction or related phenotypes. CONCLUSIONS: The study supports the involvement of genetic variation in the glutamatergic and GABAergic systems in drug addiction with partial overlap in susceptibility loci between cocaine and heroin addiction. PMID- 26277531 TI - Effect of wound infiltration with ropivacaine or bupivacaine analgesia in breast cancer surgery: A meta-analysis of randomized controlled trials. AB - BACKGROUND: Although not completely painless, breast-conserving surgery is considerably less painful than modified radical mastectomy. Local anesthetics are speculated to reduce postoperative pain when placed at the surgical site. Thus, we conducted a systematic review of randomized controlled trials to evaluate the efficacy of bupivacaine or ropivacaine analgesia for pain relief in breast cancer surgery. METHODS: PubMed, Embase, the Cochrane Library, Scopus, and the ClinicalTrials.gov registry were searched for studies published up to July 2015. Individual effect sizes were standardized, and a meta-analysis was performed to calculate a pooled effect size by using random effects models. Pain was assessed using a visual analog scale at 1, 2, 12, and 24 h postoperatively. The secondary outcomes included complications and analgesic consumption. RESULTS: We reviewed 13 trials with 1150 patients. We found no difference in postoperative pain reduction at 1, 12, and 24 h after breast cancer surgery between the experimental and control groups. The severity of pain was significantly reduced in the experimental group (weighted mean difference -0.19; 95% confidence interval: 0.39-0.00) at 2 h postoperatively. Moreover, postoperative analgesic consumption did not differ significantly between the groups. No major drug-related complication was observed in any study. CONCLUSION: Administration of the local anesthetics bupivacaine or ropivacaine during breast cancer surgery decreased pain significantly at only 2 h but did not reduce pain at 12, and 24 h postoperatively. PMID- 26277532 TI - Large pore size and controlled mesh elongation are relevant predictors for mesh integration quality and low shrinkage--Systematic analysis of key parameters of meshes in a novel minipig hernia model. AB - BACKGROUND: Prosthetic mesh implants in hernia repair are frequently used based on the fact that lower recurrence rates are detected. However, an undesirable side effect is persistent foreign body reaction that drives adhesions and shrinkage among other things in the course of time. Thereby a variety of meshes have been created in an attempt to alleviate these side effects, and particular relating to shrinkage, the ideal mesh has not been developed. Large pore size is one of the properties to get better ingrowth of the implants but could also be a risk factor to shrinkage behavior. The aim of this preclinical study was to determine optimal pore size based on mesh integration and shrinkage in a hernia minipig model. METHODS: Twenty female minipigs were each implanted at four abdominal retromuscular sites with meshes (designed and knitted specifically for this study) that had various weights and pore sizes, but similar weave. At 3 and 21 weeks post-operation, ten pigs each were euthanized. Mesh integration and shrinkage were evaluated through macroscopic observation, biomechanical testing and histopathological analysis. RESULTS: The large pore meshes (6.1-6.6 mm(2)) showed significantly better integration than small pore (0.9-1.1 mm(2)) counterparts, by biomechanical testing and histological assessment. This was independent of mesh weight. The lightweight small pore mesh exhibited significantly more shrinkage than any of the other meshes, while the three dimensional heavyweight large pore mesh exhibited the least shrinkage. Mesh shrinkage and elongation at 50 Newton (N) as one parameter of the implant structural stability appeared to be strongly interrelated. CONCLUSION: Tissue ingrowth of meshes depends on increasing pore size. Macroporous mesh design >1.5 mm diameter appears to be optimal in terms of mesh integration. Lightweight meshes with a large pore size on one hand and a lack of structural stability on the other hand drives mesh shrinkage. High stretchability (Elongation >50 N) induces higher shrinkage and therefore elongation at 50 N appears to be a new parameter to estimate mesh shrinkage. Three-dimensional mesh constructions relate to the lowest shrinkage behavior caused by higher structure stability. PMID- 26277533 TI - Predicting success of single step hysteroscopic myomectomy: A single centre large cohort study of single myomas. AB - INTRODUCTION: Submucous myomas represent one of the main indications of operative hysteroscopy. Hysteroscopic resection of submucous fibroids should be a simple, well-tolerated and effective procedure and ideally accomplished in in only one surgical step. METHODS: Retrospective cohort single Centre study of 1244 women undergoing hysteroscopic myomectomy. Data analysis included patients' and the myomas characteristics. A multiple logistic regression was carried out in order to assess which variables were able to determine a multiple step procedure. RESULTS: 1090 myomas (87.62%) were completely resected in a single-step procedure (SS group) whereas a multiple-step procedure (MS group) was needed for the removal of 154 fibroids (12.38%). The mean size of myomas resected in the SS group was 22.83 +/- 9.36 mm whereas fibroids of the MS group measured 29.67 +/- 10.76 mm. The overall feasibility of hysteroscopic myomectomy in one surgical procedure was 88.28%. All hysteroscopic myomectomies of G0 fibroids were completed in a single step. The chance of success to accomplish the treatment in a single-step for G1 and G2 myomas were 88.59% and 82.55%, respectively. The multivariate analysis revealed an inverse correlation between age and multiple step procedures and size of myomas were all directly correlated to multiple step procedures. CONCLUSION: The grading, the size of the myomas and the age of patients play a crucial role in completing the hysteroscopic myomectomy in a single step. Only the diameter greater than 3 cm in G2 myomas is correlated to a higher risk of a multiple procedure. PMID- 26277534 TI - Clozapine in schizophrenia and its association with treatment satisfaction and quality of life: Findings of the three national surveys on use of psychotropic medications in China (2002-2012). AB - OBJECTIVE: We examined the time trends and correlates of clozapine use in schizophrenia patients in China. METHOD: A total of 14,013 patients with schizophrenia treated in 45 psychiatric hospitals/centers nationwide were interviewed in 2002, 2006 and 2012. Patients' socio-demographic and clinical characteristics including psychopathology, medication side effects, satisfaction with treatment and quality of life (QOL) were recorded in a standardized fashion. RESULTS: Clozapine was used in 32.9% of the whole sample; with corresponding figures of 39.7%, 32.5% and 26.4% in 2002, 2006 and 2012 (p<0.001). Families of clozapine users had lower satisfaction with treatment than those of the non clozapine group, without significant differences with respect to patients' treatment satisfaction and mental or physical QOL. In multiple logistic regression analyses, compared to the non-clozapine group, patients on clozapine had an earlier age of onset, longer illness duration, more global illness severity and drug-induced central nervous system, gastrointestinal and other side effects, lower antipsychotic doses, less delusions and hallucinations, more negative symptoms, were more likely male, inpatients, to have a family history of psychiatric disorders, receive treatments in regional centers and receive antipsychotic polypharmacy, but less likely to have health insurance and receive first-generation antipsychotics and benzodiazepines (R(2)=0.498, p<0.001). CONCLUSIONS: Clozapine was used in one-third of schizophrenia patients in China, with decreasing frequency since 2002. Patients prescribed clozapine had multiple markers of greater global illness severity/chronicity and decreased satisfaction with treatment by the families, but similar QOL and less delusions and hallucinations than patients not prescribed clozapine. PMID- 26277535 TI - Brain correlates of verbal fluency in subthreshold psychosis assessed by functional near-infrared spectroscopy. AB - The prevalence of subthreshold psychotic symptoms in the general population has gained increasing interest as a possible precursor of psychotic disorders. The goal of the present study was to evaluate whether neurobiological features of subthreshold psychotic symptoms can be detected using verbal fluency tasks and functional near-infrared spectroscopy (fNIRS). A large data set was obtained from the Zurich Program for Sustainable Development of Mental Health Services (ZInEP). Based on the SCL-90-R subscales 'Paranoid Ideation' and 'Psychoticism' a total sample of 188 subjects was assigned to four groups with different levels of subthreshold psychotic symptoms. All subjects completed a phonemic and semantic verbal fluency task while fNIRS was recorded over the prefrontal and temporal cortices. Results revealed larger hemodynamic (oxy-hemoglobin) responses to the phonemic and semantic conditions compared to the control condition over prefrontal and temporal cortices. Subjects with high subthreshold psychotic symptoms exhibited significantly reduced hemodynamic responses in both conditions compared to the control group. Further, connectivity between prefrontal and temporal cortices revealed significantly weaker patterns in subjects with high subthreshold psychotic symptoms compared to the control group, possibly indicating less incisive network connections associated with subthreshold psychotic symptoms. The present findings provide evidence that subthreshold forms of psychotic symptoms are associated with reduced hemodynamic responses and connectivity in prefrontal and temporal cortices during verbal fluency that can be identified using fNIRS. PMID- 26277536 TI - Conservative Management of Segmental Multicystic Dysplastic Kidney in Children. AB - OBJECTIVE: To assess the clinical characteristics and natural course of segmental multicystic dysplastic kidney (MCDK). METHODS: We retrospectively analyzed the medical records of 40 patients (43 renal units) diagnosed as having segmental MCDK between January 2002 and June 2014. Segmental MCDK was classified as typical when it was localized to the upper pole of a duplex collecting system, and otherwise as atypical. We investigated involution, associated anomalies requiring surgery, and complications of segmental MCDK. RESULTS: Of 43 renal units, 23 were typical and 20 were atypical. During 71.5 (interquartile range: 37.5-84.1) months of median follow-up period, complete and partial involution were observed in 48% and 26% of the typical group and 30% and 35% of the atypical group, respectively. In the typical group, involution was complete significantly earlier (P = .048) and ipsilateral anomalies were more frequently observed (P = .002). The initiation point of involution and contralateral anomalies were not different in the two groups. Hypertension developed in 1 case with contralateral MCDK and 1 case with contralateral renal agenesis. CONCLUSION: Segmental MCDK is not a rare disease entity, and conservative treatment appears to be sufficient with thorough follow-up, including regular monitoring of blood pressure and renal function, and with ultrasonography. PMID- 26277537 TI - Cardioprotective effects of timosaponin B II from Anemarrhenae asphodeloides Bge on isoproterenol-induced myocardial infarction in rats. AB - The aim of the present study was to investigate the cardioprotective effects of Timosaponin B II (TB), a main bioactive constituent from Anemarrhenae asphodeloides Bge, on an isoproterenol (ISO)-induced myocardial infarction model in rats and explore its underlying mechanisms. Rats were treated with TB (50 mg/kg, 100 mg/kg) or diltiazem hydrochloride (DH, 5 mg/kg) by gastric gavage for five days. At the 4th and 5th days, myocardial injury was induced by ISO injection (85 mg/kg) at an interval of 24 h for 2 consecutive days. After the induction, rats were anaesthetized with pentobarbital sodium (30 mg/kg) to record the electrocardiogram. Our research showed that ISO administration resulted in significant elevations in the ST-segment, the levels of cardiac injury biomarkers creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), and concentrations of serum proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha). Pretreatment with TB significantly reversed these alterations induced by ISO challenge. The cardioprotective effects of TB were further proved by the histopathological examination. Exploration of the underlying mechanisms of its actions revealed that TB pretreatment restored the ISO-induced decrease of super oxide dismutase (SOD) and the increase of malondialdehyde (MDA). Meanwhile, we found that the enhancement of antioxidant defense system might be associated with the increased heme oxygenase isoform 1 (HO-1) induction and activated nuclear respiratory factor 2 (Nrf-2) translocation. Furthermore, the present research also demonstrated that nuclear translocation of Nrf-2 and subsequent HO 1 expression might be associated with nuclear factor kappa B (NF-kappaB) pathway activation. Taken together, our finding demonstrated that TB might have a potential benefit in preventing ischemic heart diseases like myocardial infarction. PMID- 26277538 TI - Protection of Quercetin against Triptolide-induced apoptosis by suppressing oxidative stress in rat Leydig cells. AB - Triptolide (TP) is a diterpene triepoxide with variety biological activities, such as anti-inflammatory, anti-cancerogenic, immunomodulatory and pro-apoptotic activities. However, its clinical application was limited by potential toxicity. Quercetin (Que) is a member of flavonoids with anti-oxidant effects. In this study, we aimed to demonstrate the protective effect of Que in TP-induced oxidative stress and decrease of testosterone generation in reproductive damage. Leydig cells were treated with TP (20, 40 and 60 nM), which caused obvious oxidative stress increasing intracellular ROS, decreasing activities and expressions of GPx and SOD. Apoptosis was resulted from depolarization of mitochondrial membrane potential (DeltaPsim) and release of cytochrome C (Cyt-C) showing increase of BAX/Bcl-2 ratio, caspase-3 and caspase-9. Treatment of Que (5 MUM) prior to triptolide could restore all the TP-induced alteration in a certain dose range indicating that the oxidative stress might be one reason of TP-induced reproductive toxic effect. These results suggest that the compatibility with Que might reduce the TP-induced reproductive toxicity, which provide a probability to extend the usage of TP. PMID- 26277539 TI - High affinity and covalent-binding microtubule stabilizing agents show activity in chemotherapy-resistant acute myeloid leukemia cells. AB - Treatment failure in acute myeloid leukemia (AML) is frequently due to the persistence of a cell population resistant to chemotherapy through different mechanisms, in which drug efflux via ATP-binding cassette (ABC) proteins, specifically P-glycoprotein, is one of the most recognized. However, disappointing results from clinical trials employing inhibitors for these transporters have demonstrated the need to adopt different strategies. We hypothesized that microtubule targeting compounds presenting high affinity or covalent binding could overcome the effect of ABC transporters. We therefore evaluated the activity of the high-affinity paclitaxel analog CTX-40 as well as the covalent binder zampanolide (ZMP) in AML cells. Both molecules were active in chemosensitive as well as in chemoresistant cell lines overexpressing P glycoprotein. Moreover, ZMP or CTX-40 in combination with daunorubicin showed synergistic killing without increased in vitro hematopoietic toxicity. In a primary AML sample, we further demonstrated that ZMP and CTX-40 are active in progenitor and differentiated leukemia cell populations. In sum, our data indicate that high affinity and covalent-binding anti-microtubule agents are active in AML cells otherwise chemotherapy resistant. PMID- 26277540 TI - Phytotoxic mechanisms of bur cucumber seed extracts on lettuce with special reference to analysis of chloroplast proteins, phytohormones, and nutritional elements. AB - Bioherbicides from plant extracts are an effective and environmentally friendly method to prevent weed growth. The present investigation was aimed at determining the inhibitory effect of bur cucumber seed extracts (BSE) on lettuce plant growth. Bur cucumber seeds were ground with water, and two different concentrations of seed extracts (10% and 20%) were prepared and applied to lettuce plants. Decreased plant height, number of leaves, leaf length, leaf width, anProd. Type: FTPd leaf area were found in lettuce exposed to BSE as compared with controls. A significant reduction in lettuce biomass was observed in 20% BSE-treated plants due to the presence of higher amounts of phenolic content in the extracts. Moreover, a significant inhibitory chemical, 2-linoleoyl glycerol, was identified in BSE extracts. The mechanism of plant growth inhibition was assayed in lettuce proteins by 2-dimensional electrophoresis (2 DE) and the LC-MS/MS method. In total, 57 protein spots were detected in plants treated with 20% BSE and control plants. Among these, 39 proteins were down regulated and 18 proteins were up-regulated in plants exposed to 20% BSE as compared with controls. The presence of low levels of chlorophyll a/b binding protein and oxygen-evolving enhancer protein 1 in BSE-exposed plants reduced photosynthetic pigment synthesis and might be a reason for stunted plant growth. Indeed, the plant-growth stimulating hormone gibberellin was inhibited, and synthesis of stress hormones such as abscisic acid, jasmonic acid, and salicylic acid were triggered in lettuce by the effects of BSE. Uptake of essential nutrients, Ca, Fe, Mg, K, S, and Mo, was deficient and accumulation of the toxic ions Cu, Zn, and Na was higher in BSE-treated plants. The results of this study suggest that extracts of bur cucumber seeds can be an effective eco-friendly bioherbicide for weed control that work by inhibiting mechanisms of photosynthesis and regulating phytohormones and nutritional elements. PMID- 26277541 TI - Short-term cadmium exposure induces stress responses in frog (Pelophylax bergeri) skin organ culture. AB - There have been a few studies on the negative effects of pollutants on amphibian skin, the first structural barrier that interacts with the environment and its potential contaminants. In this study an ex vivo skin organ culture from the amphibian Pelophylax bergeri was used to evaluate cell stress responses induced by short-term exposure to cadmium (Cd), a toxic heavy metal known to be an environmental hazard to both humans and wildlife. Histopathological studies were carried out on skin explants using light microscopy and changes in the expression of stress proteins, such as Metallothionein (MT) and Heat shock proteins (HSPs), were investigated by Real-time RT-PCR. Results revealed that amphibian skin reacts to Cd-induced stress by activating biological responses such as morphological alterations and dose- and time-dependent induction of Mt and Hsp70 mRNA expression, suggesting their potential role as biomarkers of exposure to Cd. This work provides a basis for a better understanding of the tissue-specific responses of amphibian skin as a target organ to Cd exposure and its in vitro use for testing potentially harmful substances present in the environment. PMID- 26277542 TI - Amino acid management in cancer. AB - Amino acids have a dual role in cellular metabolism, as they are both the building blocks for protein synthesis and intermediate metabolites which fuel other biosynthetic reactions. Recent work has demonstrated that deregulation of both arms of amino acid management are common alterations seen in cancer. Among the most highly consumed nutrients by cancer cells are the amino acids glutamine and serine, and the biosynthetic pathways that metabolize them are required in various cancer subtypes and the object of current efforts to target cancer metabolism. Also altered in cancer are components of the machinery which sense amino acid sufficiency, nucleated by the mechanistic target of rapamycin (mTOR), a key regulator of cell growth via modulation of key processes including protein synthesis and autophagy. The precise ways in which altered amino acid management supports cellular transformation remain mostly elusive, and a fuller mechanistic understanding of these processes will be important for efforts to exploit such alterations for cancer therapy. PMID- 26277543 TI - MYC and metabolism on the path to cancer. AB - The MYC proto-oncogene is frequently deregulated in human cancers, activating genetic programs that orchestrate biological processes to promote growth and proliferation. Altered metabolism characterized by heightened nutrients uptake, enhanced glycolysis and glutaminolysis and elevated fatty acid and nucleotide synthesis is the hallmark of MYC-driven cancer. Recent evidence strongly suggests that Myc-dependent metabolic reprogramming is critical for tumorigenesis, which could be attenuated by targeting specific metabolic pathways using small drug like molecules. Understanding the complexity of MYC-mediated metabolic re-wiring in cancers as well as how MYC cooperates with other metabolic drivers such as mammalian target of rapamycin (mTOR) will provide translational opportunities for cancer therapy. PMID- 26277544 TI - Oncogenes strike a balance between cellular growth and homeostasis. AB - Altered tumor cell metabolism is now firmly established as a hallmark of human cancer. Downstream of oncogenic events, metabolism is re-wired to support cellular energetics and supply the building blocks for biomass. Rapid, uncontrolled proliferation results in tumor growth beyond the reach of existing vasculature and triggers cellular adaptations to overcome limiting nutrient and oxygen delivery. However, oncogenic activation and metabolic re-programming also elicit cell intrinsic stresses, independent of the tumor microenvironment. To ensure metabolic robustness and stress resistance, pro-growth signals downstream of oncogene activation or tumor suppressor loss simultaneously activate homeostatic processes. Here, we summarize recent literature describing the adaptive mechanisms co-opted by common oncogenes, including mTOR, MYC, and RAS. Recurrent themes in our review include: (1) coordination of oncogene-induced changes in protein and lipid metabolism to sustain endoplasmic reticulum homeostasis, (2) maintenance of mitochondrial functional capacity to support anabolic metabolism, (3) adaptations to sustain intracellular metabolite concentrations required for growth, and (4) prevention of oxidative stress. We also include a discussion of the hypoxia inducible factors (HIFs) and the AMP dependent protein kinase (AMPK)--stress sensors that are co-opted to support tumor growth. Ultimately, an understanding of the adaptations required downstream of specific oncogenes could reveal targetable metabolic vulnerabilities. PMID- 26277546 TI - The locoregional recurrence post-mastectomy for ductal carcinoma in situ: Incidence and risk factors. AB - BACKGROUND: The objective of this retrospective study was to determine the incidence of recurrence of breast cancer after mastectomy for ductal carcinoma in situ (DCIS) in our institution, and to evaluate the associated risk factors while comparing them to those proposed in the literature. METHODS: The files of 218 patients who had undergone mastectomy for pure DCIS or DCIS with micro-invasion at Centre Eugene Marquis between January 2003 and November 2013 were compared for: age at diagnosis, type of mastectomy and immediate reconstruction, tumor characteristics, and the evaluation of the sentinel axillary lymph node. The mean follow-up period was 30.5 months. RESULTS: In a mean period of 39.13 months, 8 patients (3.67%) developed a recurrence post-mastectomy, 2 of whom with distant metastasis. Two others developed distant metastases subsequently during treatment. All 4 died due to progression of metastases, while the other 4 are alive and disease-free after treatment. The only risk factor was young age at initial diagnosis (<40 years). None of the other factors described in the literature, such as high grade or diffuse disease, comedo-necrosis, positive margins or micro-invasion were statistically significant. CONCLUSION: The recurrence of breast cancer after mastectomy for DCIS is rare, however, it carries a high mortality rate for those who do relapse. Patients who have high risk factors such as young age at diagnosis and high risk tumor factors should be followed closely for signs of recurrence and/or metastasis. PMID- 26277545 TI - Pyruvate kinase: Function, regulation and role in cancer. AB - Pyruvate kinase is an enzyme that catalyzes the conversion of phosphoenolpyruvate and ADP to pyruvate and ATP in glycolysis and plays a role in regulating cell metabolism. There are four mammalian pyruvate kinase isoforms with unique tissue expression patterns and regulatory properties. The M2 isoform of pyruvate kinase (PKM2) supports anabolic metabolism and is expressed both in cancer and normal tissue. The enzymatic activity of PKM2 is allosterically regulated by both intracellular signaling pathways and metabolites; PKM2 thus integrates signaling and metabolic inputs to modulate glucose metabolism according to the needs of the cell. Recent advances have increased our understanding of metabolic regulation by pyruvate kinase, raised new questions, and suggested the possibility of non canonical PKM2 functions to regulate gene expression and cell cycle progression via protein-protein interactions and protein kinase activity. Here we review the structure, function, and regulation of pyruvate kinase and discuss how these properties enable regulation of PKM2 for cell proliferation and tumor growth. PMID- 26277548 TI - Cholecalciferol supplementation improves suppressive capacity of regulatory T cells in young patients with new-onset type 1 diabetes mellitus - A randomized clinical trial. AB - It is unknown if cholecalciferol is able to modify defects in regulatory T cells (Tregs) in type 1 diabetes (T1D). In this randomized, double-blind, placebo controlled trial 30 young patients with new-onset T1D were assigned to cholecalciferol (70IU/kgbodyweight/day) or placebo for 12months. Tregs were determined by FACS-analysis and functional tests were assessed with ex vivo suppression co-cultures at months 0, 3, 6 and 12. Suppressive capacity of Tregs increased (p<0.001) with cholecalciferol from baseline (-1.59+/-25.6%) to 3 (30.5+/-39.4%), 6 (44.6+/-23.8%) and 12months (37.2+/-25.0%) and change of suppression capacity from baseline to 12months was significantly higher (p<0.05) with cholecalciferol (22.2+/-47.2%) than placebo (-16.6+/-21.1%). Serum calcium and parathormone stayed within normal range. This is the first study, which showed that cholecalciferol improved suppressor function of Tregs in patients with T1D and vitamin D could serve as one possible agent in the development of immunomodulatory combination therapies for T1D. PMID- 26277547 TI - Abnormal white matter connections between medial frontal regions predict symptoms in patients with first episode schizophrenia. AB - INTRODUCTION: The medial orbitofrontal cortex (mOFC) and rostral part of anterior cingulate cortex (rACC) have been suggested to be involved in the neural network of salience and emotional processing, and associated with specific clinical symptoms in schizophrenia. Considering the schizophrenia dysconnectivity hypothesis, the connectivity abnormalities between mOFC and rACC might be associated with clinical characteristics in first episode schizophrenia patients (FESZ). METHODS: After parcellating mOFC into the anterior and posterior part, diffusion properties of the mOFC-rACC white matter connections for 21 patients with FESZ and 21 healthy controls (HCs) were examined using stochastic tractography, one of the most effective Diffusion Tensor Imaging (DTI) methods for examining tracts between adjacent gray matter (GM) regions. RESULTS: Fractional anisotropy (FA) reductions were observed in bilateral posterior, but not anterior mOFC-rACC connections (left: p < .0001; right: p < .0001) in FESZ compared to HCs. In addition, reduced FA in the left posterior mOFC-rACC connection was associated with more severe anhedonia-asociality (rho = -.633, p = .006) and total score (rho = -.520, p = .032) in the Scale for the Assessment of Negative Symptoms (SANS); reduced FA in the right posterior mOFC-rACC connection was associated with more severe affective flattening (rho = -.644, p = .005), total score (rho = -.535, p = .027) in SANS, hallucinations (rho = -.551, p = .018), delusions (rho = -.632, p = .005) and total score (rho = -.721, p = .001) in the Scale for the Assessment of Positive Symptoms (SAPS) in FESZ. CONCLUSIONS: The observed white matter abnormalities within the connections between mOFC and rACC might be associated with the psychopathology of the early stage of schizophrenia. PMID- 26277549 TI - Frequency of copy number abnormalities in common genes associated with B-cell precursor acute lymphoblastic leukemia cytogenetic subtypes in Brazilian children. AB - Copy number alterations (CNAs) in genes committed to B-cell precursors have been associated with poor survival in subgroups of patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). We investigated submicroscopic alterations in a series of 274 Brazilian children with BCP-ALL by multiplex ligation-dependent probe amplification and evaluated their correlation with clinical and laboratory features. The relevance of overlapping CNA abnormalities was also explored. Deletions/amplifications in at least one gene were identified in 83% of the total series. In children older than 2 years, there was a predominance of CNAs involving deletions in IKZF1, CDKN2A, and CDKN2B, whereas the pseudoautosomal region 1 (PAR1) had deletions that were found more frequently in infants (P <0.05). Based on the cytogenetic subgroups, favorable cytogenetic subgroups showed more deletions than other subgroups that occurred simultaneously, specifically ETV6 deletions (P <0.05). TCF3-PBX1 was frequently deleted in RB1, and an absence of deletions was observed in IKZF1 and genes localized to the PAR1 region. The results corroborate with previous genome-wide studies and aggregate new markers for risk stratification of BCP-ALL in Brazil. PMID- 26277550 TI - Congenital coronary artery anomalies in Kawasaki Disease. PMID- 26277552 TI - Generation of recombinant destabilase-lysozyme from medicinal leeches in three different expression systems. AB - Destabilase-lysozyme (mlDL) is an enzyme secreted by the salivary gland cells of medicinal leeches. Destabilase-lysozyme possesses lysozyme and isopeptidase activities. We generated recombinant destabilase-lysozyme isoform 2 in three expression systems, i.e., in the bacteria Escherichia coli, in the yeast Pichia pastoris, and in the human cell line Expi293F. In E. coli, we generated both polypeptide in inclusion bodies that was later undergone to the refolding and soluble protein that had been fused with the chaperone SlyD. The chaperone was later cleaved by a specific TEV-protease. In cultures of the yeast P. pastoris and the human cell line Expi293F, the soluble form of destabilase-lysozyme was accumulated in the culture media. For the generated enzymes, we determined the lysozyme, isopeptidase and fibrinolytic activities and tested their general antimicrobial effects. The comparisons of the enzymes generated in the different expression systems revealed that all of the destabilase-lysozymes obtained in the soluble forms possessed equal levels of lysozyme, isopeptidase and fibrinolytic activities that exceeded several to ten times the levels of the same activities of the destabilase-lysozyme renaturated from the inclusion bodies. A similar pattern of the differences in the levels of the general antimicrobial effects was observed for the destabilase-lysozymes generated in the soluble form and as inclusion bodies. PMID- 26277553 TI - Monocyte chemoattractant protein-1 gene (MCP-1) polymorphisms are associated with risk of premature coronary artery disease in Mexican patients from the Genetics of Atherosclerotic Disease (GEA) study. AB - The CC chemokine monocyte chemoattractant protein (MCP)-1/CCL2 is involved in the formation, progression, and destabilization of atheromatous plaques and plays an essential role in postinfarction remodeling. The aim of the present study was to evaluate the role of MCP-1 gene polymorphisms as susceptibility markers for premature coronary artery disease (CAD) and cardiovascular risk factors in the Mexican population. Four MCP-1 gene polymorphisms (rs1024611, rs2857654, rs3760396, and rs1024610) were genotyped by 5' exonuclease TaqMan assays in a group of 1072 patients with premature CAD, and 1082 healthy unrelated controls (with negative calcium score by computed tomography) seeking for associations with premature CAD and other metabolic and cardiovascular risk factors using logistic regression analyses. MCP-1 polymorphism frequencies were similar in premature CAD patients and healthy controls. When the analysis included only those premature CAD patients without type 2 diabetes mellitus (T2DM), the rs1024610 polymorphism was associated with increased risk of developing premature CAD under dominant and additive models adjusted by age and gender (OR=1.33, Pdom=0.040 and OR=1.34, Padd=0.027). The effect of the MCP-1 polymorphisms on various metabolic cardiovascular risk factors and metabolic parameters was explored separately in controls, and premature CAD. In this analysis adjusted by age and gender, the rs3760396 CC genotype was associated with low levels of gamma glutamyl transpeptidase (P=0.002), whereas, the rs1024610 TT genotype was associated with decreased risk of T2DM (P=0.035) in premature CAD patients. One haplotype (CATG) was associated with increased risk of developing premature CAD (OR=1.44, P=0.0019). In summary, in our study, the rs1024610 polymorphism was associated with increased risk of developing premature CAD only in those patients without T2DM. The four MCP-1 polymorphisms were in high linkage disequilibrium and one haplotype was significantly associated with risk of developing premature CAD. PMID- 26277551 TI - Inflammatory and cardiac biomarkers are differentially expressed in clinical stages of Chagas disease. AB - BACKGROUND: Chagas disease has a long clinically silent period following Trypanosoma cruzi infection and before development of overt clinical pathology; detectable biomarkers of infection and pathogenesis are urgently needed. We tested 22 biomarkers known to be associated with cardiomyopathy to evaluate if a biomarker signature could successfully classify T. cruzi seropositive subjects into clinical Chagas disease stage groups. METHODS: This cross-sectional retrospective case-control study enrolled T. cruzi seropositive blood donors (BD) who were further characterized as having chronic Chagas cardiomyopathy (CC-BD) or not (nonCC-BD) and seronegative (SN) control donors; we also included clinically diagnosed Chagas cardiomyopathy patients (CC-P). All subjects underwent a health history questionnaire, medical examination, electro- and echocardiograms (ECG and Echo) and phlebotomy. Biomarkers were measured on blinded samples by luminex bead array and Ortho VITROS. RESULTS: A clear biomarker pattern was observed only in more severe cardiac disease; this pattern included significantly elevated levels of inflammatory cytokines IFN-gamma, IL-6, IL-10 and TNF-alpha and soluble cardiovascular disease biomarkers CK-MB, troponin, myoglobin, VCAM and NTproBNP while there were lower levels of MPO, PAI-1, and MCP-1. The markers determined to be the most predictive of disease by ROC curve analysis were NTproBNP and T. cruzi PCR status. CONCLUSIONS: Although many biomarkers demonstrated increased or decreased concentrations among the clinical forms of Chagas disease, NTproBNP and T. cruzi PCR were the only tests that would independently be of clinical value for disease staging, in concert with ECG, Echo and clinical assessments. PMID- 26277554 TI - Extracellular ATP induces unconventional release of glyceraldehyde-3-phosphate dehydrogenase from microglial cells. AB - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key glycolytic enzyme that is predominantly localized in the cytoplasm. However, recent studies have suggested that GAPDH is released by various cells and that extracellular GAPDH is involved in the regulation of neuritogenesis in neuronal cells. It has also been reported that GAPDH is expressed on the surfaces of macrophages and functions as a transferrin receptor. However, since GAPDH is a leaderless protein the mechanisms by which it reaches the extracellular environment remain unclear. Here, we examined the role of P2X7 receptor (P2X7R), an ATP-gated cation channel, in the unconventional release of GAPDH from microglial cells, the resident macrophages in the brain. The activation of P2X7R by ATP triggered GAPDH release from lipopolysaccharide (LPS)-primed microglial cells. ATP-induced microvesicle formation, exosome release, and K(+) efflux followed by caspase-1 activation are likely involved in the GAPDH release, but ATP-induced dilatation of membrane pores and lysosome exocytosis are not. It was also demonstrated that exogenous GAPDH facilitated LPS-induced phosphorylation of p38 MAP kinase in microglial cells. These findings suggest that P2X7R plays an important role in the unconventional release of GAPDH from microglial cells, and the GAPDH released into the extracellular space might be involved in the regulation of the neuroinflammatory response in the brain. PMID- 26277555 TI - [Dexmedetomidine and propofol infusion on sedation characteristics in patients undergoing sciatic nerve block in combination with femoral nerve block via anterior approach]. AB - OBJECTIVE: Dexmedetomidine is an alpha-2 adrenergic agonist having wide range of effects including sedation in mammalian brain, and has analgesic as well as sympatholytic properties. This study aimed to compare the effects of dexmedetomidine and propofol infusion on sedation characteristics in patients undergoing combined sciatic nerve and femoral nerve block via anterior approach for lower limb orthopedic procedure. METHODS: Forty patients, who were between 18 and 65 years old, this study was made at anesthesiology clinic of Bagcilar training and research hospital in 08 September 2011 to 07 June 2012, and underwent surgical procedure due to fractures lateral and medial malleol, were included. Sciatic nerve and femoral nerve block were conducted with an anterior approach on all patients included in the study, with an ultrasonography. The patients were randomly divided into dexmedetomidine [Group D (n=20). 0.5MUgkg( 1)h(-1)] and propofol [Group P (n=20); 3mgkg(-1)h(-1)] infusion groups. RESULTS: The vital findings and intra-operative Ramsay sedation scale values were similar in both groups. Time taken for sedation to start and time required for sedation to become over of Group D were significantly higher than those of Group P (p<0.001 for each). CONCLUSIONS: Substitution of dexmedetomidine instead of propofol prolongs the times to start of sedation, the times to end of sedation and duration of sedation. PMID- 26277556 TI - Barlow's Mitral Valve Disease: A Comparison of Neochordal (Loop) and Edge-To-Edge (Alfieri) Minimally Invasive Repair Techniques. AB - BACKGROUND: Barlow's mitral valve (MV) disease remains a surgical challenge. We compared short- and medium-term outcomes of neochordal ("loop") versus edge-to edge ("Alfieri") minimally invasive MV repair in patients with Barlow's disease. METHODS: From January 2009 to April 2014, 123 consecutive patients with Barlow's disease (defined as bileaflet billowing or prolapse [or both], excessive leaflet tissue, and annular dilatation with or without calcification) underwent minimally invasive MV operations for severe mitral regurgitation (MR) at our institution. Three patients (2.4%) underwent MV replacement during the study period and were excluded from subsequent analysis. The loop MV repair technique was used in 68 patients (55.3%) and an edge-to-edge repair was performed in 44 patients (35.8%). Patients who underwent a combination of these 2 techniques (n = 8 [6.5%]) were excluded. The median age was 48 years, and 62.5% of patients were men. Concomitant procedures included closure of a patent foramen ovale or atrial septal defect (n = 19), tricuspid valve repair (n = 5), and atrial fibrillation ablation (n = 15). Follow-up was performed 24.7 +/- 17 months postoperatively and was 98% complete. RESULTS: No deaths occurred perioperatively or during follow up. Aortic cross-clamp time (64.1 +/- 17.6 minutes versus 95.9 +/- 29.5 minutes) and cardiopulmonary bypass (CPB) time (110.0 +/- 24.2 minutes versus 146.4 +/- 39.1 minutes) were significantly shorter (p < 0.001) in patients who received edge-to-edge repair. Although patients who underwent edge-to-edge repair received a larger annuloplasty ring (38.6 +/- 1.5 mm versus 35.8 +/- 2.7 mm; p < 0.001), the early postoperative resting mean gradients were higher (3.3 +/- 1.2 mm Hg versus 2.6 +/- 1.2 mm Hg; p = 0.007) and the mitral orifice area tended to be smaller in this group (2.8 +/- 0.7 cm(2) versus 3.0 +/- 0.7 cm(2); p = 0.06). The amount of residual MR was similar between groups (0.3 +/- 0.6 versus 0.6 +/- 1.0 for edge-to-edge versus loop procedures, respectively; p = 0.08). More than mild MR requiring early MV reoperation was present in 3 patients who underwent loop procedures (4.4%) and in no patients who had edge-to-edge procedures (p = 0.51). During follow-up, 2 patients (1 in each group) required MV replacement for severe MR. The 4-year freedom from MV reoperation was 92.8% +/- 5.0% in the Alfieri group compared with 90.9% +/- 4.6% in the loop group (p = 0.94). CONCLUSIONS: Minimally invasive MV repair can be accomplished with excellent early and medium term outcomes in patients with Barlow's disease. The edge-to-edge (Alfieri) repair can be performed with reduced operative times when compared with the loop technique, but it results in mildly increased transvalvular gradients and mildly decreased valve opening areas without any difference in residual MR. PMID- 26277557 TI - Outcomes of Open Repair of Mycotic Descending Thoracic and Thoracoabdominal Aortic Aneurysms. AB - BACKGROUND: The purpose of this study was to evaluate the short- and intermediate term outcomes of open repair of mycotic thoracic and thoracoabdominal aneurysms. Contemporary surgical and perioperative techniques were utilized. METHODS: From November 1997 to May 2014, 14 consecutive patients underwent open repair of descending thoracic (n = 9, 64.3%) and thoracoabdominal (n = 5, 35.7%) mycotic aortic aneurysms. All procedures were performed through the left side of the chest. Infected tissue was completely debrided and excised. Aortic continuity was restored in situ with a Dacron prosthesis (Macquet Corp, Oakland, NJ). Soft tissue coverage of the prosthesis was performed when anatomy and patient condition permitted. Perioperative outcomes, intermediate-term survival, and reinfection rates were examined. RESULTS: All patients presented with either aneurysm-related symptoms or a clinical picture of sepsis. Diagnosis was confirmed utilizing computed tomography imaging. Mean age was 66 +/- 13 years, 8 patients (57.1%) were male, and mean aneurysm size was 5.9 +/- 1.3 cm. All patients were hypertensive, 3 (21.4%) had prior coronary revascularization, 7 (50%) had chronic pulmonary disease, 5 (35.7%) had diabetes mellitus, and 2 (14.3%) had end-stage renal disease requiring dialysis. Twelve patients (85.7%) had aneurysm-related pain, and 9 (64.3%) of them had contained rupture. Mean time from onset of illness to surgery was 36 days (range, 0 to 153). On preoperative blood cultures, 4 (28.6%) grew Staphylococcus aureus, 4 (28.6%) grew gram negative organisms, 2 (14.3%) grew mycobacterium, and 4 cultures (28.6%) had negative results. Empiric broad-spectrum antibiotics were initiated on all patients and adjusted based on final cultures. A majority of patients underwent repair utilizing a clamp-and-sew technique (n = 10, 71.4%); the remainder (n = 4, 28.6%) required repair under profound hypothermic circulatory arrest. After radical debridement of the infected tissue, grafts were placed in the normal anatomic position; 6 (42.9%) patients had additional soft tissue coverage, 5 (35.7%) utilizing an omental flap and 1 (7.1%), a serratus muscle flap. There was 1 in-hospital death (7.1%) secondary to ischemic bowel. Four patients (28.6%) required tracheostomy, and 1 (7.1%) had recurrent nerve injury. None of the patients incurred spinal cord injury, stroke, or new onset renal failure requiring dialysis. After surgery, all patients were given 6 weeks of intravenous antibiotics. Lifelong suppression therapy was maintained with oral antibiotics. There were no episodes of prosthetic graft infection on follow-up. Univariate analysis revealed that New York Heart Association functional class, diabetes, and preoperative renal dysfunction were preoperative risk factors for major adverse events. Mean follow-up time was 26.5 months (median 8.2; range, 1 to 142). Actuarial 5-year survival was 71%. CONCLUSIONS: Open repair of mycotic descending thoracic and thoracoabdominal aortic aneurysms remains the gold standard of therapy. Aggressive intraoperative debridement with in situ prosthetic reconstruction permits a high rate of success in this very high risk cohort of patients. Lifelong antibiotic suppression therapy may prevent late prosthetic graft infection. PMID- 26277558 TI - Surgical Resection of Rare Esophageal Cancers. AB - BACKGROUND: Although surgical resection of adenocarcinoma or squamous cell carcinoma of the esophagus is standard practice, the treatment strategy for other malignant rare esophageal cancers is still under debate. The aim of this study was to examine the treatment of rare malignant esophageal cancers and to evaluate the survival of these patients. METHODS: A retrospective review of all esophagectomies performed at Mayo Clinic from 1980 to 2014 (approximately 4,000 cases) identified 24 patients with histologic features other than adenocarcinoma or squamous cell carcinoma. Their medical records were reviewed for demographics, presenting symptoms, evaluation, surgical management, pathologic features, and short-term and long-term outcome. RESULTS: Pathologic identifications included small cell carcinoma, lymphoma, and undifferentiated carcinoma in 4 (16.7%) patients each and neuroendocrine, melanoma, leiomyosarcoma, sarcomatoid, sarcoma, and gastrointestinal stromal tumor in 2 (8.3%) patients each. The most common presenting symptoms included dysphasia in 91.7% patients (22/24), pain in 75.0% (18/24), and weight loss in 62.5% (15/24). Preoperative evaluation included barium swallow in 91.7% (22/24), computed tomography in 91.7% (22/24), positron emission tomography in 54.2% (13/24), esophagogastroduodenoscopy in 100% (24/24), and endoscopic ultrasonography in 29.2% (7/24) patients. The location of the tumor was at the gastroesophageal junction in 41.7% (10/24). There was no operative mortality, and 13 patients (54.16%) had at least one postoperative adverse event. The 1-year survival after esophagectomy was 69.7%, the 5-year survival was 42.7%, and the 10-year survival was 37.4%. CONCLUSIONS: Esophageal cancer with pathologic features other than squamous cell carcinoma or adenocarcinoma is rare. Esophagectomy for rare types of malignant esophageal cancers should be considered part of the effective treatment paradigm. PMID- 26277559 TI - Coexisting Mitral Regurgitation Impairs Survival After Transcatheter Aortic Valve Implantation. AB - BACKGROUND: It remains unclear whether coexisting and untreated mitral regurgitation (MR) affects survival after transcatheter aortic valve implantation (TAVI) for aortic stenosis (AS). To summarize contemporary evidence, we performed the first metaanalysis of adjusted observational studies reporting post-TAVI mortality in patients with various grades of MR. METHODS: MEDLINE and EMBASE were searched until February 2015, with a bibliographic review of secondary sources. Eligible studies were observational studies enrolling patients undergoing TAVI for AS and reporting adjusted odds ratios (ORs), hazard ratios (HRs), or both for early (30-day or in-hospital) all-cause mortality, overall all-cause mortality, or both in patients with apparent (significant) versus unapparent (nonsignificant) MR as outcomes. RESULTS: Sixteen eligible studies enrolling a total of 13,672 patients undergoing TAVI for AS were identified and included. Pooled analyses of eight studies (representing 9,356 patients) and 14 studies (representing 7,405 patients) respectively demonstrated a statistically significant increase in early (OR 2.17; 95% confidence interval [CI] 1.50 to 3.14; p < 0.0001) and overall all-cause mortality (HR 1.81; 95% CI 1.37 to 2.40; p < 0.0001) in patients with apparent relative to unapparent MR. The exclusion of any single study from the analyses did not substantively alter the overall results of our analyses, and there was no evidence of significant publication bias. CONCLUSIONS: Coexisting and untreated apparent (usually moderate or severe) MR appears to be associated with an increase in both early and overall mortality after TAVI for AS. PMID- 26277560 TI - Transcatheter Aortic Valve Replacement Results in Improvement of Pulmonary Function in Patients With Severe Aortic Stenosis. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) has been identified as a risk factor for morbidity and mortality after transcatheter aortic valve replacement (TAVR). We hypothesized that a portion of pulmonary dysfunction in patients with severe aortic stenosis may be of cardiac origin, and has potential to improve after TAVR. METHODS: A retrospective analysis was made of consecutive TAVR patients from April 2008 to October 2014. Of patients who had pulmonary function testing and serum B-type natriuretic peptide data available before and after TAVR, 58 were found to have COPD (26 mild, 14 moderate, and 18 severe). Baseline variables and operative outcomes were explored along with changes in pulmonary function. Multiple regression analyses were performed to adjust for preoperative left ventricular ejection fraction and glomerular filtration rate. RESULTS: Comparison of pulmonary function testing before and after the procedure among all COPD categories showed a 10% improvement in forced vital capacity (95% confidence interval: 4% to 17%) and a 12% improvement in forced expiratory volume in 1 second (95% confidence interval: 6% to 19%). There was a 29% decrease in B type natriuretic peptide after TAVR (95% confidence interval: -40% to -16%). An improvement of at least one COPD severity category was observed in 27% of patients with mild COPD, 64% of patients with moderate COPD, and 50% of patients with severe COPD. There was no 30-day mortality in any patient group. CONCLUSIONS: In patients with severe aortic stenosis, TAVR is associated with a significant improvement of pulmonary function and B-type natriuretic peptide. After TAVR, the reduction in COPD severity was most evident in patients with moderate and severe pulmonary dysfunction. PMID- 26277561 TI - Early Surgical Outcomes of En Bloc Resection Requiring Vertebrectomy for Malignancy Invading the Thoracic Spine. AB - BACKGROUND: En bloc vertebral resection of locally invasive T4 lung cancers led to the development of a surgical sequence for resection; posterior stabilization, reposition, thoracotomy, lobectomy, vertebrectomy, and anterior spine stabilization in 1 procedure. This technique expanded indications for vertebrectomy to selected patients with sarcoma and metastatic disease. We review our experience to identify areas for clinical improvement. METHODS: Operative case logs were cross-checked with billing data from 2003 to 2014 with Current Procedural Terminology (CPT, American Medical Association) codes for vertebrectomy. Thirty-two cases involving en bloc resection of malignancy invading at least 1 thoracic vertebra were selected. Outcomes data were analyzed using summary statistics. RESULTS: Series includes 14 men and 18 women, median age 50 years. Twenty-five patients (78%) received preoperative chemoradiation. Nineteen total and 13 partial vertebrectomy were performed. Average number of vertebrae resected was 1.6 (range, 1 to 4). Median operative length was 8.5 hours (range, 2.8 to 14.5), mean blood loss 923 mL (SD +/- 477 mL), and median length of stay 8 days (range, 3 to 56). Major morbidity followed 56% of cases. Thirty day mortality was 3%. Overall median survival was 43.6 months, 1-year survival was 73.6%, and 5-year survival was 40.3%. CONCLUSIONS: En bloc vertebrectomy for malignant disease is feasible. Our 1 stage and 2 team approach allows completion of the operation within a standard day, but is associated with long operative time. Complication rates may improve with decreased operative times. Review of available data warrants future prospective studies. PMID- 26277562 TI - Pathologic Upstaging in Patients Undergoing Resection for Stage I Non-Small Cell Lung Cancer: Are There Modifiable Predictors? AB - BACKGROUND: A substantial proportion of patients with clinical stage I non-small cell lung cancer (NSCLC) have more advanced disease on final pathologic review. We studied potentially modifiable factors that may predict pathologic upstaging. METHODS: Data of patients with clinical stage I NSCLC undergoing resection were obtained from the National Cancer Database. Univariate and multivariate analyses were performed to identify variables that predict upstaging. RESULTS: From 1998 to 2010, 55,653 patients with clinical stage I NSCLC underwent resection; of these, 9,530 (17%) had more advanced disease on final pathologic review. Of the 9,530 upstaged patients, 27% had T3 or T4 tumors, 74% had positive lymph nodes (n > 0), and 4% were found to have metastatic disease (M1). Patients with larger tumors (38 mm vs 29 mm, p < 0.001) and a delay greater than 8 weeks from diagnosis to resection were more likely to be upstaged. Upstaged patients also had more lymph nodes examined (10.9 vs 8.2, p < 0.001) and were more likely to have positive resection margins (10% vs 2%, p < 0.001). Median survival was lower in upstaged patients (39 months vs 73 months). Predictors of upstaging in multivariate regression analysis included larger tumor size, delay in resection greater 8 weeks, positive resection margins, and number of lymph nodes examined. There was a linear relationship between the number of lymph nodes examined and the odds of upstaging (1 to 3 nodes, odds ratio [OR] 2.01; >18 nodes OR 6.14). CONCLUSIONS: Pathologic upstaging is a common finding with implications for treatment and outcomes in clinical stage I NSCLC. A thorough analysis of regional lymph nodes is critical to identify patients with more advanced disease. PMID- 26277563 TI - Following the intracellular localization of the iab-8ncRNA of the bithorax complex using the MS2-MCP-GFP system. AB - Homeotic genes are aligned on the chromosome in the order of the segments that they specify along the antero-posterior axis of the fly. In general the genes affecting the more posterior segments repress the more anterior genes, a phenomenon known as "posterior dominance". There is however a noticeable exception to this rule in the central nervous system of Drosophila melanogaster where the posterior Abd-B gene does not repress the immediately more anterior abd A gene. Instead, abd-A repression is accomplished by a 92 kb-long ncRNA (the iab 8ncRNA) that is transcribed from the large inter-genic region between abd-A and Abd-B. This iab-8ncRNA encodes a microRNA to repress abd-A and also a second redundant repression mechanism acting in cis and thought to be transcriptional interference with the abd-A promoter. Using in situ hybridization, a previous work suggested that the iab8ncRNA transcript forms discrete foci restricted to the nuclear periphery and that this localization may be important for its function. In order to better characterize the intra-cellular localization of the iab-8ncRNA we used the MS2-MCP system, which allows fluorescent labeling of RNA in cells and relies on the interaction between GFP-tagged MS2 coat protein (MCP GFP) and MS2 RNA stem loops. Our results indicate that the large foci seen in previous studies correspond to the site of iab8ncRNA transcription and that the foci seen may simply be an indication of the level of transcription at the locus. We find no evidence to suggest that this localization is important for its function on abd-A repression. We discuss the idea that the iab-8ncRNA may be a relic of a more general ancient mechanism of posterior dominance during the emergence of the hox clusters that was mediated by transcriptional interference. PMID- 26277564 TI - Socs36E limits STAT signaling via Cullin2 and a SOCS-box independent mechanism in the Drosophila egg chamber. AB - The Suppressor of Cytokine Signaling (SOCS) proteins are critical, highly conserved feedback inhibitors of signal transduction cascades. The family of SOCS proteins is divided into two groups: ancestral and vertebrate-specific SOCS proteins. Vertebrate-specific SOCS proteins have been heavily studied as a result of their strong mutant phenotypes. However, the ancestral clade remains less studied, a potential result of genetic redundancies in mammals. Use of the genetically tractable organism Drosophila melanogaster enables in vivo assessment of signaling components and mechanisms with less concern about the functional redundancy observed in mammals. In this study, we investigated how the SOCS family member Suppressor of Cytokine Signaling at 36E (Socs36E) attenuates Janus Kinase/Signal Transducer and Activator of Transcription (Jak/STAT) activation during specification of motile border cells in Drosophila oogenesis. We found that Socs36E genetically interacts with the Cullin2 (Cul2) scaffolding protein. Like Socs36E, Cul2 is required to limit the number of motile cells in egg chambers. We demonstrated that loss of Cul2 in the follicle cells significantly increased nuclear STAT protein levels, which resulted in additional cells acquiring invasive properties. Further, reduction of Cul2 suppressed border cell migration defects that occur in a Stat92E-sensitized genetic background. Our data incorporated Cul2 into a previously described Jak/STAT-directed genetic regulatory network that is required to generate a discrete boundary between cell fates. We also found that Socs36E is able to attenuate STAT activity in the egg chamber when it does not have a functional SOCS box. Collectively, this work contributes mechanistic insight to a Jak/STAT regulatory genetic circuit, and suggests that Socs36E regulates Jak/STAT signaling via a Cul2-dependent mechanism, as well as by a Cullin-independent manner, in vivo. PMID- 26277565 TI - Susceptibility of helminth species from horses against different chemical compounds in Brazil. AB - By means of parasitological necropsies, the present study aimed to evaluate, in six experiments, the degree of susceptibility or resistance of different helminth species which naturally infect horses to ivermectin 0.2 mg/kg, abamectin 0.2 mg/kg, moxidectin 0.4 mg/kg, trichlorfon 35 mg/kg, ivermectin 0.2 mg/kg+praziquantel 2.5 mg/kg, abamectin 0.2 mg/kg+praziquantel 2.5 mg/kg and ivermectin 0.2 mg/kg+6.6 mg/kg pyrantel. At experimental day zero, the horses were allocated to treatment groups based on average counts of strongylid eggs per gram of feces (EPG) obtained on days -3, -2 and -1. Oxyuris sp. infections were confirmed as positive or negative. All the animals in the six experiments were naturally infected by this helminth species. Each group (control or treated) consisted of six animals. All the assessed Habronema muscae populations analyzed were susceptible to ivermectin, abamectin and moxidectin. Of the six Trichostrongylus axei populations, four were susceptible to ivermectin, abamectin, moxidectin, trichlorfon and ivermectin+praziquantel, and two were resistant to abamectin+praziquantel and ivermectin+pyrantel. Both Strongyloides westeri populations analyzed were susceptible to ivermectin, abamectin, moxidectin and abamectin+praziquantel. For O. equi, resistance was found in four different populations treated with ivermectin, abamectin, moxidectin, trichlorfon and ivermectin+praziquantel. Only combinations of abamectin+praziquantel and ivermectin+pyrantel were effective against this parasite species. All the large strongyles diagnosed in the present study (Strongyus edentatus, Strongyus vulgaris and Triodontophorus serratus) were susceptible to all the chemicals tested, with the exception of trichlorfon. Of the Cyathostominae populations, one was diagnosed as resistant to ivermectin and another to trichlorfon. The remaining populations from this nematode group were considered to be sensitive to ivermectin, abamectin, moxidectin, ivermectin+praziquantel, abamectin+praziquantel and ivermectin+pyrantel. New studies should be performed in different regions to evaluate the efficacy of trichlorfon in others field populations of helminthes. PMID- 26277566 TI - Metronidazole-but not IL-10 or prednisolone-rescues Trichuris muris infected C57BL/6 IL-10 deficient mice from severe disease. AB - Trichuris muris infected C57BL/6 mice are a frequently studied model of immune mediated resistance to helminths. Our objective was to characterize dose dependent gastrointestinal (GI) disease and pathology due to Trichuris in C57BL/6 mice with varying degrees of IL-10 sufficiency. These mice can serve as a model for other animals (dogs, cattle) and humans where IL-10 polymorphisms have been associated with disease susceptibility and may affect susceptibility to whipworm. C57BL/6 IL-10(+/+), IL-10(+/-) and IL-10(-/-) mice were infected with T. muris (J strain) in a dose response study. T. muris produced dose-dependent disease in IL 10(-/-) mice. Ninety percent of mice receiving the high dose (75 ova) had severe disease necessitating early euthanasia, while the medium dose (50 ova) resulted in 100% early euthanasia of males/75% of females, and the low dose (25 ova) in 100% early euthanasia of males/25% of females. Having some IL-10 as in heterozygotes did not rescue all infected mice from effects of the high dose. 2/21 IL-10(-/-), 1/17 IL-10(+/-), and 0/17 IL-10(+/+) mice in the high dose group had severe peritonitis and extra-intestinal bacteria confirmed by fluorescent 16S rDNA analysis of peritoneal organ surfaces. Three of twenty one IL-10(-/-) had demonstrable extra-intestinal T. muris adults. Although free from viral pathogens, 12/21 IL-10(-/-), 6/17 IL-10(+/-), and 4/17 IL-10(+/+) infected mice had hepatitis, while control mice of all genotypes did not. Mice had evidence of inflammation of serosal surfaces of liver, spleen and GI tract even when extraintestinal Trichuris were not found. Blinded histopathology scoring revealed that even when infected IL-10(-/-) mice displayed few, if any, clinical signs, levels of gut inflammation did not vary significantly from those mice euthanized early due to severe disease. To examine whether antibiotics or corticosteroids could reverse severe disease and lesions, IL-10(-/-) mice infected with T. muris were treated with metronidazole or prednisolone prior to and throughout 40 days of infection. Mice given prednisolone had severe disease and lesions with the highest mortality rate. Mice given metronidazole had a significantly lower mortality rate than those given prednisolone, but GI lesions were of similar severity and distribution including peritonitis. Mortality was associated with extraintestinal worms and bacteria and further supported a role for enteric bacteria in this pathogenesis. PMID- 26277567 TI - Detection of Leishmania major and Leishmania tropica in domestic cats in the Ege Region of Turkey. AB - Leishmaniosis is a group of diseases caused by different species of Leishmania parasites in mammalian species. The aim of the present study was to investigate the presence of Leishmania spp. DNA in cats using real time polymerase chain reaction (RT-PCR) assays targeting internal transcribed spacer (ITS1) and heat shock protein 70 gene (Hsp70) regions with Leishmania species-specific primers and probes. Blood samples were collected from 147 cats (73 female; 74 male) in the endemic regions for zoonotic visceral leishmaniasis in the western provinces of Turkey and analyzed using two RT-PCR assays. Additionally, Hsp70 RT-PCR products were sequenced. ELISA assays for feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) were also carried out for 145 of the 147 samples. Overall, 13/147 (8.84%) cats were positive for Leishmania by RT-PCR (4 L. major and 9 L. tropica). FIV and FeLV antibody and/or antigen was detected in 4 and 5 cats among Leishmania DNA positives, respectively. To the best of our knowledge, this study is the first to investigate and report the presence of L. major and L. tropica infections in a large group of domestic cats in Turkey. The results obtained indicate that species identification of Leishmania is essential for epidemiological understanding and that clinical signs alone are not indicative for leishmaniosis in cats, as it is in dogs. This study suggests that extensive research should be carried out in cat populations in order to fully understand the role of cats in the epidemiology of the disease. PMID- 26277568 TI - The taruca (Hippocamelus antisensis) and the red brocket deer (Mazama americana) as intermediate hosts of Taenia hydatigena in Peru, morphological and molecular evidence. AB - In the present report metacestodes were collected from the mesentery of a taruca (Hippocamelus antisensis) and from the omentum of a red brocket deer (Mazama americana) in Peru. Various metacestodes parameters, including rostellar hook characteristics, were measured. Molecular analysis was performed to amplify the mitochondrial cytochrome c oxidase subunit 1 gene from metacestode isolates. Metacestodes were identified as T. hydatigena by morphology and molecular methods. This constitutes the first molecular detection of T. hydatigena metacestodes in the taruca and the red brocket deer and demonstrates that these animal species are natural intermediate hosts for this parasite. PMID- 26277569 TI - Safety of reduced anti-thrombotic strategies in HeartMate II patients: A one-year analysis of the US-TRACE Study. AB - BACKGROUND: Patients with bleeding complications during left ventricular assist device (LVAD) support often require a reduction in the recommended warfarin plus aspirin regimen. To characterize those who can be safely managed with a reduced anti-thrombotic strategy, the TRACE (STudy of Reduced Anti-Coagulation/Anti platelEt Therapy in Patients with the HeartMate II LVAS) study was initiated in the United States (U.S.) and Europe. METHODS: The TRACE U.S. arm enrolled HeartMate II (HMII; Thoratec) outpatients on a regimen of reduced anti-thrombotic therapy (RT), defined as vitamin K antagonist (warfarin) only, aspirin only, or no anti-thrombotic agent. The indication for RT, changes in anti-thrombotic therapies, and patient outcomes after RT were documented. Results for patients reaching 12 months or outcome are presented here. RESULTS: Between April 2012 and June 2013, 100 HMII outpatients (85% men) on RT (median age 64.5 [interquartile range, 32, 82] years, 61% with ischemic etiology, 69% destination therapy) were enrolled from 9 U.S. sites. The primary reason for RT initiation was in response to a bleeding event (82%). Pharmacotherapy at RT initiation included warfarin only (38%), aspirin only (28%), or no anti-thrombotic agent (34%). Freedom from ischemic stroke at 1 year was 93.8% +/- 2.5%, and freedom from device thrombosis was 92.7% +/- 2.7%. Despite RT, a subsequent bleeding event occurred in 52%. CONCLUSIONS: Reducing anti-thrombotic therapies in response to bleeding among HMII patients was achievable but may be associated with a higher risk for device thrombosis. Furthermore, despite an RT strategy, bleeding often will persist in those prone to such events. PMID- 26277570 TI - Identify, isolate, inform: Background and considerations for Ebola virus disease preparedness in U.S. ambulatory care settings. AB - Public health activities to identify and monitor persons at risk for Ebola virus disease in the United States include directing persons at risk to assessment facilities that are prepared to safely evaluate for Ebola virus disease. Although it is unlikely that a person with Ebola virus disease will unexpectedly present to a nonemergency ambulatory care facility, the Centers for Disease Control and Prevention have provided guidance for this setting that can be summarized as identify, isolate, and inform. PMID- 26277571 TI - Seroprevalence of cytomegalovirus IgG antibodies among pregnant women in Japan from 2009-2014. AB - BACKGROUND: Human cytomegalovirus (CMV) is a major cause of congenital infection. The seroprevalence of maternal CMV IgG antibodies among Japanese women is decreasing. In this study, we assessed the rate of and risk factors for CMV infection. This article includes a description of a method for the prevention of CMV infection. METHODS: Medical records of 7,074 women who delivered a baby at our hospital were retrospectively reviewed. For seronegative patients, preventive educational materials were provided, and CMV IgG antibody levels were reassessed during late pregnancy. Congenital infection in neonates from seroconverted mothers was determined by urine analysis. RESULTS: The overall CMV IgG seropositivity rate was 69.1%. The prevalence of CMV IgG increased with age and parity. In a multivariate logistic regression analysis, parity remained an independent determinant of CMV IgG seropositivity. The seroconversion rate for CMV IgG antibody during pregnancy was 0.37%. Neonatal congenital CMV infection occurred in 37.5% of seroconverted women. The risk of primary CMV infection in mothers during their first pregnancy was 7.0%, with an average follow-up period of 2.1 years. CONCLUSION: We found that parity was an independent determinant of CMV IgG seropositivity, suggesting that child-rearing may be a high risk factor for maternal CMV infection. The provision of information on hygiene may be an effective and inexpensive method for preventing CMV infection. PMID- 26277572 TI - Personal protective equipment for the Ebola virus disease: A comparison of 2 training programs. AB - BACKGROUND: Personal protective equipment (PPE) for preventing Ebola virus disease (EVD) includes basic PPE (B-PPE) and enhanced PPE (E-PPE). Our aim was to compare conventional training programs (CTPs) and reinforced training programs (RTPs) on the use of B-PPE and E-PPE. METHODS: Four groups were created, designated CTP-B, CTP-E, RTP-B, and RTP-E. All groups received the same theoretical training, followed by 3 practical training sessions. RESULTS: A total of 120 students were included (30 per group). In all 4 groups, the frequency and number of total errors and critical errors decreased significantly over the course of the training sessions (P < .01). The RTP was associated with a greater reduction in the number of total errors and critical errors (P < .0001). During the third training session, we noted an error frequency of 7%-43%, a critical error frequency of 3%-40%, 0.3-1.5 total errors, and 0.1-0.8 critical errors per student. The B-PPE groups had the fewest errors and critical errors (P < .0001). CONCLUSION: Our results indicate that both training methods improved the student's proficiency, that B-PPE appears to be easier to use than E-PPE, that the RTP achieved better proficiency for both PPE types, and that a number of students are still potentially at risk for EVD contamination despite the improvements observed during the training. PMID- 26277573 TI - Decreasing vancomycin utilization in a neonatal intensive care unit. AB - This study evaluated the efficacy of education versus audit and feedback in decreasing vancomycin utilization. Data were collected prospectively from October 1, 2012-April 30, 2014 over the following 3 periods: baseline, after education and introduction of a late-onset sepsis treatment guideline, and after prospective audit-feedback to physicians. Vancomycin utilization and administration duration >3 days significantly decreased with education and guideline use, but it was not affected by addition of audit and feedback. PMID- 26277574 TI - The effectiveness of UV-C radiation for facility-wide environmental disinfection to reduce health care-acquired infections. AB - BACKGROUND: Health care-acquired infections (HAIs) constitute an increasing threat for patients worldwide. Potential contributors of HAIs include environmental surfaces in health care settings, where ultraviolet-C radiation (UV C) is commonly used for disinfection. This UV-C intervention-based pilot study was conducted in a hospital setting to identify any change in the incidence of HAIs before and after UV-C intervention, and to determine the effectiveness of UV C in reducing pathogens. METHODS: In a hospital in Culver City, CA, during 2012 2013, bactericidal doses of UV-C radiation (254 nm) were delivered through a UV-C based mobile environmental decontamination unit. The UV-C dosing technology and expertise of the specifically trained personnel were provided together as a dedicated service model by a contracted company. The incidence of HAIs before and after the intervention period were determined and compared. RESULTS: The dedicated service model dramatically reduced HAIs (incidence difference, 1.3/1000 patient-days, a 34.2% reduction). Reductions in the total number and incidence proportions (28.8%) of HAIs were observed after increasing and maintaining the coverage of UV-C treatments. CONCLUSION: The dedicated service model was found to be effective in decreasing the incidence of HAIs, which could reduce disease morbidity and mortality in hospitalized patients. This model provides a continuously monitored and frequently UV-C-treated patient environment. This approach to UV-C disinfection was associated with a decreased incidence of HAIs. PMID- 26277575 TI - Molecular phylogeny of Squaliformes and first occurrence of bioluminescence in sharks. AB - BACKGROUND: Squaliform sharks represent approximately 27 % of extant shark diversity, comprising more than 130 species with a predominantly deep-dwelling lifestyle. Many Squaliform species are highly specialized, including some that are bioluminescent, a character that is reported exclusively from Squaliform sharks within Chondrichthyes. The interfamiliar relationships within the order are still not satisfactorily resolved. Herein we estimate the phylogenetic interrelationships of a generic level sampling of "squaloid" sharks and closely related taxa using aligned sequences derived from a targeted gene capture approach. The resulting phylogenetic estimate is further used to evaluate the age of first occurrence of bioluminescence in Squaliformes. RESULTS: Our dataset comprised 172 putative ortholog exon sequences. Phylogenetic estimates result in a fully resolved tree supporting a monophyletic lineage of Squaliformes excluding Echinorhinus. Non-luminous Squalidae are inferred to be the sister to a clade comprising all remaining Squaliform families. Our results suggest that the origin of photophores is coincident with an elevated diversification rate and the splitting of families Dalatiidae, Etmopteridae, Oxynotidae and Somniosidae at the transition of the Lower to the Upper Cretaceous. The presence of luminous organs was confirmed for the Sleeper shark genus Zameus. These results indicate that bioluminescence in sharks is not restricted solely to the families Etmopteridae and Dalatiidae as previously believed. CONCLUSIONS: The sister-clade to non luminous Squalidae comprises five families. The presence of photophores is reported for extant members of three out of these five families based on results of this study, i.e. Lantern sharks (Etmopteridae), Kitefin sharks (Dalatiidae) and Sleeper sharks (Somniosidae). Our results suggest that the origin of luminous organs arose during the rapid diversification event that gave rise to the extant Squaliform families. These inferences are consistent with the idea of diversification of Squaliform sharks being associated with the emergence of new deep-sea habitats in the Lower Cretaceous, which may have been facilitated by the evolution of bioluminescence. PMID- 26277576 TI - High Serum Uric Acid Levels Are Associated with All-Cause and Cardiovascular, but Not Cancer, Mortality in Elderly Adults. AB - OBJECTIVES: To estimate the all-cause, cardiovascular, and cancer mortality risks associated with serum uric acid levels in elderly adults. DESIGN: Cohort study. SETTING: The Annual Geriatric Health Examination Program database from 2006 to 2010. PATICIPANTS: Community-dwelling Taipei citizens aged 65 and older (N = 77,541). MEASUREMENTS: Stratified according to sex, serum uric acid levels were analyzed in quartiles and as normal versus high categories. Mortality was determined by matching cohort identifications with national death files. RESULTS: Men had significantly higher uric acid levels than women (P < .001), and mean levels increased with age (P < .001). Serum uric acid levels (normal vs high) were an independent risk factor for all-cause and cardiovascular mortality in men and women, with the strongest association found for cardiovascular mortality. The association between serum uric acid levels and cardiovascular mortality was independent of other cardiovascular risk factors such as hypertension, diabetes mellitus, hyperlipidemia, and glomerular filtration rate levels. When levels were analyzed as quartiles, men with levels in the second quartile had the lowest hazard ratios for all-cause and cardiovascular mortality. CONCLUSION: High serum uric acid levels are associated with greater risk of all-cause and cardiovascular mortality but not cancer mortality in elderly adults. Further studies are warranted to investigate the prognostic implications and potential utility in the monitoring of therapy. PMID- 26277578 TI - Hyperthyroidism induced by topical iodine. PMID- 26277577 TI - Infection is the major trigger of hemophagocytic syndrome in adult patients treated with biological therapies. AB - INTRODUCTION: Hemophagocytic syndromes (hemophagocytic lymphohistiocytosis, HLH) are characterized by a wide range of etiologies, symptoms, and outcomes, but have a common etiopathogenic pathway leading to organ damage: an excessive inflammatory response. Biological therapies have been proposed as a therapeutic option for refractory HLH, but have also been related to the development of HLH in severe immunosuppressed patients. OBJECTIVES AND METHODS: The purpose of this study was to analyze the clinical characteristics and outcomes of adult patients who developed HLH after receiving biological therapies. RESULTS: We identified 30 patients (29 from the PubMed search and one unpublished case), including 19 women and 11 men, with a mean age of 46.5 years. Underlying diseases consisted of rheumatologic/autoimmune diseases in 24 patients and hematological neoplasia in the remaining 6. Biological agents received before the development of HLH were mainly anti-TNF agents (n = 19). Search for microorganisms confirmed systemic infection in 20 (67%) patients, including Mycobacterium tuberculosis (n = 5), cytomegalovirus (CMV) (n = 4), Epstein-Barr virus (EBV) (n = 3), Histoplasma capsulatum (n = 3), Escherichia coli (n = 2), Staphylococcus aureus, Leishmania amastigotes and Brucella melitensis (n = 1, respectively); viral infections were mainly reported in inflammatory bowel disease (IBD) patients. Patients with infections had more frequently received previous immunosuppressive therapies (p = 0.036) and had lower leukocyte counts (p = 0.020) in comparison with patients without associated infections. The outcome was described in 29 patients. After a mean follow-up of 6.3 months, 8 patients died (28%) and 6 had received anti-TNF agents. There was a high mortality rate in patients aged >65 years and those with tuberculosis (62% and 60%, respectively). CONCLUSIONS: In patients receiving biological therapies who develop HLH, searching for a concomitant infectious process is mandatory, and specific surveillance for EBV/CMV infections (in patients with IBD) and for bacteria, including mycobacteria (in elderly patients receiving anti-TNF therapy), is recommended. PMID- 26277579 TI - A novel pressed porous silicon-polycaprolactone composite as a dual-purpose implant for the delivery of cells and drugs to the eye. AB - Dysfunction of corneal epithelial stem cells can result in painful and blinding disease of the ocular surface. In such cases, treatment may involve transfer of growth factor and normal adult stem cells to the ocular surface. Our purpose was to develop an implantable scaffold for the delivery of drugs and cells to the ocular surface. We examined the potential of novel composite biomaterials fabricated from electrospun polycaprolactone (PCL) fibres into which nanostructured porous silicon (pSi) microparticles of varying sizes (150-250 MUm or <40 MUm) had been pressed. The PCL fabric provided a flexible support for mammalian cells, whereas the embedded pSi provided a substantial surface area for efficient delivery of adsorbed drugs and growth factors. Measurements of tensile strength of these composites revealed that the pSi did not strongly influence the mechanical properties of the polymer microfiber component for the Si loadings evaluated. Human lens epithelial cells (SRA01/04) attached to the composite materials, and exhibited enhanced attachment and growth when the materials were coated with foetal bovine serum. To examine the ability of the materials to deliver a small-drug payload, pSi microparticles were loaded with fluorescein diacetate prior to cell attachment. After 6 hours (h), cells exhibited intracellular fluorescence, indicative of transfer of the fluorescein diacetate into viable cells and its subsequent enzymatic conversion to fluorescein. To investigate loading of large-molecule biologics, murine BALB/c 3T3 cells, responsive to epidermal growth factor, insulin and transferrin, were seeded on composite materials. The cells showed significantly more proliferation at 48 h when seeded on composites loaded with these biologics, than on unloaded composites. No cell proliferation was observed on PCL alone, indicating the biologics had loaded into the pSi microparticles. Drug release, measured by ELISA for insulin, indicated a burst followed by a slower, continuous release over six days. When implanted under the rat conjunctiva, the most promising composite material did not cause significant neovascularization but did elicit a macrophage and mild foreign body response. These novel pressed pSi-PCL materials have potential for delivery of both small and large drugs that can be released in active form, and can support the growth of mammalian cells. PMID- 26277580 TI - TIMP-1 affects the spatial distribution of dendritic processes of second-order neurons in a rat model of Retinitis Pigmentosa. AB - Retinitis Pigmentosa (RP) is an inherited disorder that may lead to blindness. In the rhodopsin S334ter-line-3 rat model of RP, the death of rods induces spatial rearrangement of cones into regular ring mosaics. Using this model, we discovered that the ring mosaics are restored to a homogeneous distribution upon application of tissue inhibitor of metalloproteinase-1 (TIMP-1). In this study, we further investigated the cone migration and spatial distribution of second-order neurons and their connections to cones in the presence or absence of TIMP-1 using immunohistochemistry to identify retinal neurons and their connections with cones. M-opsin cell bodies and their outer segments were evaluated to determine whether TIMP-1 delays the degeneration of outer segments of cones. We observed that during cone rearrangement into ring mosaics in RP retina, dendritic processes of second-order neurons undergo remodeling to maintain their synaptic connections with the cones in the rings. TIMP-1 treatment induced the cones to rearrange and dendritic processes of second-order neurons to return to a more homogeneous spatial distribution. In addition, TIMP-1 treatment protected the outer segments of cones at later stages of retinal degeneration. Our findings clearly demonstrate that despite their dramatic spatial rearrangement, cones and second-order neuron processes maintain their synaptic connections before and after TIMP-1 treatment. PMID- 26277581 TI - Photopigment self-screening and the determination of macular pigment absorbance using heterochromatic flicker photometry. AB - PURPOSE: Heterochromatic flicker photometry (HFP) is commonly used to determine macular pigment optical density (MPOD). Since HFP in this application is a locus comparison method, an identical relative spectral response at each locus is required for a perfect measure. We know this requirement cannot be strictly true since the optical density of photopigments increases as the foveal center is approached. Thus, the self-screening effect would result in an underestimate of MPOD. An earlier study concluded that the underestimate is on the order of 30%. We examined this issue by manipulating photopigment optical density, and consequently the degree of selfscreening. METHODS: A continuously exposed, 470 nm, background bleached cone photopigments over a range from 0 to 80%. MPOD was determined 10' and 30' from the foveal center. Two subjects were used in the main experiment. Five additional subjects were studied with just the 0% and 80% bleach levels. Spectral measures were obtained at 0% and 70% bleach levels for the two primary subjects. RESULTS: Subjects in the main experiment showed MPOD estimates that increased with increasing bleaching. The effect, however, was small: one observer's MPOD increased 0.08 and 0.02 for the 10' and 30' loci, respectively; the other observer's values were 0.04 and 0.01 for the same loci. Comparable values were obtained for the other five subjects using the 0% and 80% bleach conditions. Spectral measures were consistent with the findings of the main experiment. CONCLUSIONS: When self-screening is nearly abolished (80% bleach), a relatively small underestimation is revealed for the unbleached state. For the 1 degrees target we show about 2-3% underestimation. Our 20' target reveals a larger underestimate (8-9%), consistent with longer photoreceptor outer-segments nearer the foveal center. We conclude that HFP yields values essentially independent of self-screening for targets of 1 degrees diameter or greater. Smaller targets are less than 10% underestimated for near-zero bleach conditions. PMID- 26277582 TI - Programmed cell death-1 is expressed in large retinal ganglion cells and is upregulated after optic nerve crush. AB - Programmed cell death-1 (PD-1) is a key negative receptor inducibly expressed on T cells, B cells and dendritic cells. It was discovered on T cells undergoing classical programmed cell death. Studies showed that PD-1 ligation promotes retinal ganglion cell (RGC) death during retinal development. The purpose of this present study is to characterize PD-1 regulation in the retina after optic nerve crush (ONC). C57BL/6 mice were subjected to ONC and RGC loss was monitored by immunolabelling with RNA-binding protein with multiple splicing (Rbpms). Time course of PD-1 mRNA expression was determined by real-time PCR. PD-1 expression was detected with anti-PD-1 antibody on whole mount retinas. PD-1 staining intensity was quantitated. Colocalization of PD-1 and cleaved-caspase-3 after ONC was analyzed. Real-time PCR results demonstrated that PD-1 gene expression was significantly upregulated at day 1, 3, 7, 10 and 14 after ONC. Immunofluorescent staining revealed a dramatic increase of PD-1 expression following ONC. In both control and injured retinas, PD-1 tended to be up-expressed in a subtype of RGCs, whose somata size were significantly larger than others. Compared to control, PD 1 intensity in large RGCs was increased by 82% in the injured retina. None of the large RGCs expressed cleaved-caspase-3 at day 5 after ONC. Our work presents the first evidence of PD-1 induction in RGCs after ONC. This observation supports further investigation into the role of PD-1 expression during RGC death or survival following injury. PMID- 26277583 TI - Soluble extracellular matrix metalloproteinase inducer (EMMPRIN, EMN) regulates cancer-related cellular functions by homotypic interactions with surface CD147. AB - EMMPRIN (extracellular matrix metalloproteinase inducer) is a widely expressed glycoprotein and a member of the immunoglobulin superfamily which exists in both a membrane-spanning and a soluble form. Homotypic interactions of EMMPRIN underlie its multiple roles in normal development and pathological situations such as viral infections, Alzheimer's disease and cancer. This study employed a recombinant soluble, fully glycosylated EMMPRIN domain (rhsEMN) as a tool to characterize the structural basis of EMMPRIN-EMMPRIN receptor (EMNR) contacts and their functional effects on MCF-7 breast carcinoma cells. rhsEMN did not form dimers in solution but bound to surface EMMPRIN (EMN) on MCF-7 cells with high affinity and was readily internalized. The interaction interface for the homotypic contact was localized to the N-terminal Ig domain. rhsEMN exerted a stimulatory effect on proliferation of MCF-7 cells whereas it reduced cell migration in a dose-dependent manner. These effects were accompanied by an upregulation of endogenous EMMPRIN as well as of matrix metalloproteinase-14 (MMP 14), a membrane-bound protease involved in the extracellular release of soluble EMMPRIN, indicating a regulatory feedback mechanism. The proliferation-promoting activity of rhsEMN was mimicked by a novel functional antibody directed to EMMPRIN, underscoring that crosslinking of cell surface EMMPRIN (EMNR) is crucial for eliciting intracellular signalling. Addressing malignancy-related signal transduction in HEK-293 cells, we could show that rhsEMN triggers the oncogenic Wnt pathway. PMID- 26277584 TI - Stereoselective Retentive Domino Transmetalations of Secondary Alkyllithium Compounds to Functionalized Secondary Alkylcopper Reagents. AB - Functionalized secondary alkyllithium reagents obtained by I/Li exchange from the corresponding secondary alkyl iodides undergo two successive transmetalations with Me3 SiCH2 ZnBr?LiBr and CuBr?2 LiCl?Me2 S to provide functionalized secondary alkylcopper compounds with high retention of configuration. These alkylcopper derivatives react further with electrophiles such as alkynyl esters, acid chlorides, allylic chlorides, ketals, ethylene oxide, and 3 iodocyclopentanone with high retention of configuration. A related sequence of transmetalations with MeMgI and LaCl3 ?2 LiCl allows a retentive addition of secondary alkyllithium reagents to acetone. The influence of the solvent on the configurational stability of secondary alkylzinc reagents is described. PMID- 26277585 TI - Robotic-assisted laparoscopic bilio-pancreatic bypass with duodenal switch. PMID- 26277586 TI - Quality control and standardization of embryo morphology scoring and viability markers. AB - A so-called 'good-quality embryo' may be defined as an embryo that has the potential to implant into the uterine endometrium and give rise to the birth of a healthy child. A standardized and objective scoring of embryo 'quality' is therefore crucial in the classification and selection of embryos. However, embryo scoring is still being performed mainly via ocular evaluation, which often results in different interpretations of embryo quality. The addition of viability markers, such as measuring gene expression or the uptake/release of metabolites, proteins or RNA/DNA molecules in the culture media, would increase the possibility of standardized measurements. However, no single biomarker has yet been introduced into standard clinical practice, mainly due to the complexity of the techniques and the influence of biological variations and differences in culture conditions. In this paper different methods for the scoring of embryos and the possibility of standardizing and implementing quality control systems are discussed. PMID- 26277587 TI - Assisted yes, but where do we draw the line? AB - In a recent report in Reproductive Biomedicine Online by Ebner et al., a comprehensive multi-centre study was presented on the use of a calcium ionophore, A23187, to artificially activate oocytes from patients who had poor fertilization rates in previous cycles. Under physiological conditions, the calcium increase in oocytes at activation is caused by influx and release from specific stores and ion channels, and has precise temporal, quantitative and spatial patterns. Calcium ionophores may release Ca(2+) in an uncontrolled fashion from intracellular stores that would not normally be involved in the activation process. Ionophores, including A23187, have a multitude of effects on cell homeostasis, not yet defined in oocytes, that may have long-term effects, for example on gene expression. We suspect that the successful births reported by Ebner et al. are a result of the overriding influence of the injected spermatozoa, rather than the effect of the ionophore; nevertheless, such an invasive non-physiological approach to assisted reproduction techniques is worrying, especially as epigenetic effects may result in future generations. PMID- 26277588 TI - Correlation between presence of Leishmania RNA virus 1 and clinical characteristics of nasal mucosal leishmaniosis. AB - INTRODUCTION: Mucosal leishmaniosis (ML) is a severe clinical form of leishmaniosis. Complex factors related to the parasite and the host are attributed to the development of mucosal lesions. Leishmania RNA virus 1 (LRV1) can disrupt immune response, and may be the main determinant of severity of the disease; it should be investigated. OBJECTIVE: To study the existence of clinical differences between patients with ML with endosymbiosis by LRV1 and. those without it. METHODS: A cross-sectional cohort study with clinical evaluation, polymerase chain reaction (PCR) detection of Leishmania, species classification, and search of LRV1 was performed. Only patients with confirmed diagnosis of ML by positive PCR and with nasal mucosa injuries were included in this analysis. RESULTS: Out of 37 patients, 30 (81.1%) were diagnosed with Leishmania braziliensis, five (13.5%) with Leishmania guyanensis, and two (5.4%) with mixed infection of L. braziliensis and L. guyanensis. LVR1 virus was present in 26 (70.3%) of the cases. CONCLUSION: Correlation between clinical phenotype and presence of LRV1 was not observed, although the frequency of the virus is two fold higher in mucosal lesions than that found in the literature on skin lesions in the same geographical area. PMID- 26277589 TI - Efferent inhibition of otoacoustic emissions in preterm neonates. AB - INTRODUCTION: Abnormalities in auditory function of newborns may occur not only because of preterm birth, but also from the use of medications and from diseases related to prematurity. OBJECTIVE: To analyze the inhibitory effect from stimulation of the olivocochlear efferent system on transient evoked otoacoustic emissions in preterm neonates, comparing these data with those from full-term neonates. METHODS: This was a prospective, cross-sectional, contemporary cohort study with 125 neonates, pooled into two groups: full-term (72 full-term neonates, 36 females and 36 males, born at 37-41 weeks of gestational age); and preterm (53 neonates, 28 males and 25 females, born at <=36 weeks of gestational age, evaluated at the corrected gestational age of 37-41 weeks). Otoacoustic emissions were recorded using linear and nonlinear click-evoked stimuli, with and without contralateral stimulation. RESULTS: The inhibitory effect of the efferent pathway in otoacoustic emissions was different (p=0.012) between groups, and a mean reduction of 1.48dB SPL in full-term births and of 1.02dB SPL in preterm births was observed for the non-linear click-evoked stimulus. CONCLUSION: The results suggest a reduced inhibitory effect of the olivocochlear efferent system on otoacoustic emissions in preterm neonates. PMID- 26277590 TI - Analysis of pattern of occurrence of thyroid carcinoma between 2001 and 2010. AB - INTRODUCTION: An ongoing discussion is found in medical literature about the reasons for changes in thyroid carcinoma incidence patterns over the last decades. OBJECTIVE: To analyze the clinical and pathological characteristics of thyroid carcinoma cases over a decade. METHODS: Cross-sectional study over an historical cohort. Medical records of 628 thyroid cancer cases in a single center were reviewed. 597 patients were included. Microcarcinoma cases were selected for a qualitative analysis phase, in which medical records were reviewed for better understanding of thyroid nodule and thyroid cancer diagnosis process. RESULTS: An increase in the proportion of cases with thyroid cancer diagnosis was observed throughout the decade; new cases were predominantly tumors of less than 2 cm, with histopathological signs of low aggressiveness. There was an increase in proportion of cases with malignant cytological results among microcarcinomas. CONCLUSION: There is a trend for increase in thyroidectomies due to cancer in this institution, with proportional increment of cases with histopathological characteristics indicative of early disease. Among microcarcinomas, there is an increasing group represented by cancer cases that were not incidentally diagnosed, related to an enhancement in preoperative diagnostic methods. PMID- 26277591 TI - Benchmarks for the Dichotic Sentence Identification test in Brazilian Portuguese for ear and age. AB - INTRODUCTION: Dichotic listening tests should be used in local languages and adapted for the population. OBJECTIVE: Standardize the Brazilian Portuguese version of the Dichotic Sentence Identification test in normal listeners, comparing the performance for age and ear. METHODS: This prospective study included 200 normal listeners divided into four groups according to age: 13-19 years (GI), 20-29 years (GII), 30-39 years (GIII), and 40-49 years (GIV). The Dichotic Sentence Identification was applied in four stages: training, binaural integration and directed sound from right and left. RESULTS: Better results for the right ear were observed in the stages of binaural integration in all assessed groups. There was a negative correlation between age and percentage of correct responses in both ears for free report and training. The worst performance in all stages of the test was observed for the age group 40-49 years old. CONCLUSIONS: Reference values for the Brazilian Portuguese version of the Dichotic Sentence Identification test in normal listeners aged 13-49 years were established according to age, ear, and test stage; they should be used as benchmarks when evaluating individuals with these characteristics. PMID- 26277592 TI - Sedentary behavior and medical multimorbidity. AB - Emerging research demonstrates that sedentary behavior is associated with various individual chronic conditions, independent of physical activity. Despite multimorbidity (having at least 2 chronic diseases) being highly prevalent (>= 23% of adults) and associating with premature mortality, limited research has examined the association between sedentary behavior and multimorbidity, which was the purpose of this research letter. Data from the 2005-2006 NHANES were used (analyzed in 2015). A multimorbidity index variable was created indicating the number of 14 morbidities each patient had; sedentary behavior and physical activity were assessed via accelerometry. For every 60 min/day increase in sedentary behavior, participants had a higher multimorbidity index (beta(adjusted) = 0.08; 95% CI: 0.04-0.11, p<0.001) and had an 11% (OR(adjusted) = 1.11; 95% CI: 1.01-1.21; p = 0.03) increased odds of being multimorbid (i.e., having >= 2 morbidities). Sedentary behavior is associated with multimorbidity (independent of light-intensity physical activity and adherence to moderate-to vigorous physical activity guidelines), which underscores the importance of minimizing prolonged sedentary behavior (in addition to promoting physical activity) among adults. PMID- 26277593 TI - Type 2 innate lymphoid cells in induced sputum from children with severe asthma. PMID- 26277594 TI - Continuing IgG replacement therapy for hypogammaglobulinemia after rituximab--for how long? PMID- 26277597 TI - Neutrophils in respiratory syncytial virus infection: A target for asthma prevention. AB - Lower respiratory tract infections by respiratory syncytial virus (RSV) are the foremost cause of infant hospitalization and are implicated in lasting pulmonary impairment and the development of asthma. Neutrophils infiltrate the airways of pediatric patients with RSV-induced bronchiolitis in vast numbers: approximately 80% of infiltrated cells are neutrophils. However, why neutrophils are recruited to the site of viral respiratory tract infection is not clear. In this review we discuss the beneficial and pathologic contributions of neutrophils to the immune response against RSV infection. Neutrophils can limit viral replication and spread, as well as stimulate an effective antiviral adaptive immune response. However, low specificity of neutrophil antimicrobial armaments allows for collateral tissue damage. Neutrophil-induced injury to the airways during the delicate period of infant lung development has lasting adverse consequences for pulmonary architecture and might promote the onset of asthma in susceptible subjects. We suggest that pharmacologic modulation of neutrophils should be explored as a viable future therapy for severe RSV-induced bronchiolitis and thereby prevent the inception of subsequent asthma. The antiviral functions of neutrophils suggest that targeting of neutrophils in patients with RSV-induced bronchiolitis is best performed under the umbrella of antiviral treatment. PMID- 26277595 TI - Genetic errors of the human caspase recruitment domain-B-cell lymphoma 10-mucosa associated lymphoid tissue lymphoma-translocation gene 1 (CBM) complex: Molecular, immunologic, and clinical heterogeneity. AB - Three members of the caspase recruitment domain (CARD) family of adaptors (CARD9, CARD10, and CARD11) are known to form heterotrimers with B-cell lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (MALT1). These 3 CARD-BCL10-MALT1 (CBM) complexes activate nuclear factor kappaB in both the innate and adaptive arms of immunity. Human inherited defects of the 3 components of the CBM complex, including the 2 adaptors CARD9 and CARD11 and the 2 core components BCL10 and MALT1, have recently been reported. Biallelic loss-of-function mutant alleles underlie several different immunologic and clinical phenotypes, which can be assigned to 2 distinct categories. Isolated invasive fungal infections of unclear cellular basis are associated with CARD9 deficiency, whereas a broad range of clinical manifestations, including those characteristic of T- and B-lymphocyte defects, are associated with CARD11, MALT1, and BCL10 deficiencies. Interestingly, human subjects with these mutations have some features in common with the corresponding knockout mice, but other features are different between human subjects and mice. Moreover, germline and somatic gain-of-function mutations of MALT1, BCL10, and CARD11 have also been found in patients with other lymphoproliferative disorders. This broad range of germline and somatic CBM lesions, including loss-of-function and gain-of-function mutations, highlights the contribution of each of the components of the CBM complex to human immunity. PMID- 26277596 TI - Exposure to welding fumes and lower airway infection with Streptococcus pneumoniae. AB - BACKGROUND: Welders are at increased risk of pneumococcal pneumonia. The mechanism for this association is not known. The capacity of pneumococci to adhere to and infect lower airway cells is mediated by host-expressed platelet activating factor receptor (PAFR). OBJECTIVE: We sought to assess the effect of mild steel welding fumes (MS-WF) on PAFR-dependent pneumococcal adhesion and infection to human airway cells in vitro and on pneumococcal airway infection in a mouse model. METHODS: The oxidative potential of MS-WF was assessed by their capacity to reduce antioxidants in vitro. Pneumococcal adhesion and infection of A549, BEAS-2B, and primary human bronchial airway cells were assessed by means of quantitative bacterial culture and expressed as colony-forming units (CFU). After intranasal instillation of MS-WF, mice were infected with Streptococcus pneumoniae, and bronchoalveolar lavage fluid (BALF) and lung CFU values were determined. PAFR protein levels were assessed by using immunofluorescence and immunohistochemistry, and PAFR mRNA expression was assessed by using quantitative PCR. PAFR was blocked by CV-3988, and oxidative stress was attenuated by N acetylcysteine. RESULTS: MS-WF exhibited high oxidative potential. In A549 and BEAS-2B cells MS-WF increased pneumococcal adhesion and infection and PAFR protein expression. Both CV-3988 and N-acetylcysteine reduced MS-WF-stimulated pneumococcal adhesion and infection of airway cells. MS-WF increased mouse lung PAFR mRNA expression and increased BALF and lung pneumococcal CFU values. In MS WF-exposed mice CV-3988 reduced BALF CFU values. CONCLUSIONS: Hypersusceptibility of welders to pneumococcal pneumonia is in part mediated by the capacity of welding fumes to increase PAFR-dependent pneumococcal adhesion and infection of lower airway cells. PMID- 26277598 TI - Objective assessment of domestic mold contamination using quantitative PCR. PMID- 26277599 TI - Provider experiences with uterine balloon tamponade for uncontrolled postpartum hemorrhage in health facilities in Kenya. AB - OBJECTIVE: To understand provider perceptions and experiences following training in the use of a condom-catheter uterine balloon tamponade (UBT) as second-line treatment for uncontrolled postpartum hemorrhage (PPH) in health facilities in Kenya. METHODS: As part of a qualitative study, interviews of facility-based providers who had managed PPH following comprehensive PPH training were conducted between February and April 2014. Facilities were purposively sampled to represent a range of experience with UBT, facility size, and geography. Interviews continued until thematic saturation was achieved. Interview transcripts were analyzed for themes. RESULTS: Overall, 68 providers from 29 facilities were interviewed, of whom 31 reported experience with UBT placement (25 midwives, 2 clinical officers, 4 medical officers). Qualitative analysis revealed several major themes. Providers used UBT appropriately within the PPH algorithm, although the timing and clinical severity of patients varied. UBT was most commonly used when bleeding was unresponsive to uterotonics, hysterectomy was unavailable, and referral times long. Providers reported that bleeding was arrested following UBT use in all except one patient, who had a suspected coagulopathy. Most providers described UBT as technically easy to use, although three described initial balloon displacement. CONCLUSION: UBT has been readily accepted by providers at all levels of training and is being incorporated into the existing PPH management algorithm in Kenya. PMID- 26277600 TI - [Lack of correlation between retinal variables before treatment and poor functional response after focal photocoagulation in diabetic macular oedema]. AB - BACKGROUND: Although photocoagulation reduces the incidence of moderate visual loss in eyes with focal diabetic macular oedema, some eyes may lose some vision after treatment. The proportion of eyes with poor functional response after photocoagulation, and whether any retinal variable is associated with this, is unknown. OBJECTIVE: To determine the proportion of eyes with diabetic macular oedema that have a poor functional response after focal photocoagulation, and their associated features. MATERIAL AND METHODS: A non-experimental, longitudinal, comparative and retrospective study was conducted. The proportion and 95% confidence intervals (CI) of diabetics with macular oedema that had a poor functional response after focal photocoagulation (any visual loss after 6 weeks) were identified. The means of retinal variables before treatment were compared between eyes with and without a poor functional response using the Student t test for independent means. RESULTS: The study included 115 eyes of patients aged 59.3 (SD 9.24) years. Visual acuity was greater than or equal to 0.5 in 63 eyes (54.8%). A total of 33 eyes had a poor functional response after photocoagulation (28.7%, 95% CI: 13.3 to 44.1). The comparison between retinal variables and visual acuity before treatment did not show any differences between eyes with or without a poor functional response and eyes. CONCLUSION: Retinal thickening and visual acuity improved or did not change in 71.3% of eyes with diabetic macular oedema with a single photocoagulation procedure. Retinal variables that are usually evaluated were unable to identify the remaining 28.7%, which could lose vision after that treatment, and would require additional interventions. PMID- 26277601 TI - [Update on surgical treatment of primary and metastatic cutaneous melanoma]. AB - Melanoma is a common cutaneous tumour. It is of great importance due to its increasing incidence and aggressive behaviour, with metastasis to lymph nodes and internal organs. When suspecting melanoma, excisional biopsy should be performed to obtain complete histological information in order to determine the adverse factors such as ulceration, mitosis rate, and Breslow depth, which influence preoperative staging and provide data for sentinel lymph biopsy decision making. The indicated management for melanoma is wide local excision, observing recommended and well-established excision margins, depending on Breslow depth and anatomical location of the tumour. Therapeutic lymphadenectomy is recommended for patients with clinically or radiologically positive lymph nodes. This article reviews surgical treatment of melanoma, adverse histological factors, sentinel lymph node biopsy, and radical lymphadenectomy. Details are presented on special situations in which management of melanoma is different due to the anatomical location (plantar, subungual, lentigo maligna), or pregnancy. PMID- 26277602 TI - Parameter optimization method for the water quality dynamic model based on data driven theory. AB - Parameter optimization is important for developing a water quality dynamic model. In this study, we applied data-driven method to select and optimize parameters for a complex three-dimensional water quality model. First, a data-driven model was developed to train the response relationship between phytoplankton and environmental factors based on the measured data. Second, an eight-variable water quality dynamic model was established and coupled to a physical model. Parameter sensitivity analysis was investigated by changing parameter values individually in an assigned range. The above results served as guidelines for the control parameter selection and the simulated result verification. Finally, using the data-driven model to approximate the computational water quality model, we employed the Particle Swarm Optimization (PSO) algorithm to optimize the control parameters. The optimization routines and results were analyzed and discussed based on the establishment of the water quality model in Xiangshan Bay (XSB). PMID- 26277603 TI - Renewables-to-reefs: Response to Fowler et al. PMID- 26277604 TI - A high BMI is a risk factor in younger patients with de novo acute myelogenous leukemia. AB - Overweight and obese patients have an increased risk to develop several malignancies and, additionally, body mass index (BMI) impacts on outcome in several solid tumors. However, little is known for AML. We analyzed a cohort of 3526 patients with AML treated in three prospective multicenter trials within the German Study Alliance Leukemia. In multivariate analyses, we identified BMI as an independent risk factor for both DFS (HR 1.014, P = 0.0217) and OS (HR 1.015, P < 0.0036). Interestingly, overweight and obesity seemed to be a risk factor predominantly in patients with de novo AML younger than 65 yr with intermediate risk and adverse cytogenetics. Overweight with a BMI >=25 kg/m2 best discriminated the worse outcome and led to an absolute reduction in long-term survival of 5-7% in the group of all younger patients (3-yr OS 39.9% vs. 47.3%; 10-yr OS 28.7% vs. 33.8%, P = 0.0002). Additionally, response to induction therapy was significantly reduced in these patients (76.9% vs. 82.8%, P < 0.0001). Thus, in younger patients with de novo AML, overweight and obesity are risk factors for impaired response to induction therapy, DFS and OS. This effect is, in part but not fully, explained by dose reduction such as dose-capping at a body surface area of 2 m2. PMID- 26277605 TI - 17-(allylamino)-17-demethoxygeldanamycin drives Hsp70 expression but fails to improve morphological or functional recovery in injured skeletal muscle. AB - The stress inducible 70 kDa heat shock protein (Hsp70) is instrumental to efficient morphological and functional recovery following skeletal muscle injury because of its roles in protein quality control and molecular signalling. Therefore, in attempt to improve recovery, Hsp70 expression was increased with 17 (allylamino)-17-demethoxygeldanamycin (17-AAG) prior to and following an intramuscular injection of barium chloride (BaCl2) into the tibialis anterior (TA) of healthy young mice. To assess recovery, regenerating fibre cross sectional area (CSA) of the TA and in vivo peak isometric torque produced by the anterior crural muscles (TA, extensor digitorum longus and extensor hallucis muscles) were analyzed for up to 3 weeks after the injury. Because treatment of 17-AAG and Hsp70 are known to influence inflammatory and myogenic signalling, tumor necrosis factor-alpha (TNF-alpha) and myogenin content were also assessed. This study reports that 17-AAG was effective at up-regulating Hsp70 expression, increasing content fivefold in the uninjured muscle. However, this significant increase in Hsp70 content did not enhance morphological or functional recovery following the injury, as the return of regenerating fibre CSA and in vivo peak isometric torque did not differ compared to that of the injured muscle from the vehicle treated mice. Treatment with 17-AAG also altered TNF-alpha and myogenin content, increasing both to a greater extent after the injury. Together, these findings demonstrate that although 17-AAG may alter molecular makers of regeneration, it does not improve recovery following BaCl2-induced skeletal muscle injury in healthy young mice. PMID- 26277606 TI - The Effectiveness of Pemetrexed Monotherapy Depending on Polymorphisms in TS and MTHFR Genes as Well as Clinical Factors in Advanced NSCLC Patients. AB - In NSCLC, second-line chemotherapy using pemetrexed or docetaxel has limited efficacy and should be dedicated to selected groups of patients. Pemetrexed is an antifolate compound with the ability to inhibit enzymes (TS, DHFR and GARFT) involved in pyrimidine and purine synthesis. The objective of this study was to evaluate the association between polymorphisms of TS and MHFR genes and clinical outcomes in NSCLC patients treated with pemetrexed monotherapy. DNA was isolated from peripheral blood of 72 non-squamous NSCLC patients treated with pemetrexed. Using PCR and RFLP methods, the variable number of tandem repeats (VNTR), the G > C SNP in these repeats and insertion/deletion polymorphism of TS gene as well as 677C > T SNP in MTHFR gene were analyzed and correlated with disease control rate, progression-free survival and overall survival (OS) of NSCLC patients. Carriers of 2R/3R(G), 3R(C)/3R(G), 3R(G)/3R(G) genotypes showed significantly more frequent early progression than carriers of 2R/2R, 2R/3R(C), 3R(C)/3R(C) genotypes of TS gene (p < 0.05). Among carriers of triple 28 bp tandem repeats (3R) in TS gene and C/C genotype of MTHFR gene a significantly shorter OS was observed (HR = 3.07; p = 0.003). In multivariate analysis, significantly higher risk of death was observed in carriers of both 3R/3R genotype in TS and C/C genotype in 677C > T SNP in MTHFR (HR = 3.85; p < 0.005) as well as in patients with short duration of response to first-line chemotherapy (HR = 2.09; p < 0.005). Results of our study suggested that genetic factors may have a high predictive and prognostic value (even greater than clinical factors) for patients treated with pemetrexed monotherapy. PMID- 26277608 TI - Towards dropout training for convolutional neural networks. AB - Recently, dropout has seen increasing use in deep learning. For deep convolutional neural networks, dropout is known to work well in fully-connected layers. However, its effect in convolutional and pooling layers is still not clear. This paper demonstrates that max-pooling dropout is equivalent to randomly picking activation based on a multinomial distribution at training time. In light of this insight, we advocate employing our proposed probabilistic weighted pooling, instead of commonly used max-pooling, to act as model averaging at test time. Empirical evidence validates the superiority of probabilistic weighted pooling. We also empirically show that the effect of convolutional dropout is not trivial, despite the dramatically reduced possibility of over-fitting due to the convolutional architecture. Elaborately designing dropout training simultaneously in max-pooling and fully-connected layers, we achieve state-of-the-art performance on MNIST, and very competitive results on CIFAR-10 and CIFAR-100, relative to other approaches without data augmentation. Finally, we compare max pooling dropout and stochastic pooling, both of which introduce stochasticity based on multinomial distributions at pooling stage. PMID- 26277607 TI - Combination of Praziquantel and Aspirin Minimizes Liver Pathology of Hamster Opisthorchis viverrini Infection Associated Cholangiocarcinoma. AB - Opisthorchiasis is one of the major risk factors for cholangiocarcinoma (CCA) in northeastern Thailand. An effective drug for killing this parasite is praziquantel. Recently, several reports have shown that with frequent use, praziquantel may itself be a CCA risk and can cause liver cell damage from an immunopathological response after parasite death. Aspirin has many properties including anti-inflammation and anti-cancer. Therefore, we use of aspirin (As) and praziquantel (Pz) to improve hepatobiliary system function in hamsters infected with Opisthorchis viverrini (OV) and or administered N nitrosodimethylamine (ND). Livers of OVNDAsPz, appeared healthy macroscopically, suggesting slow progression of cholangiocarcinoma evident by extent of fibrosis and bile duct cell proliferation was less than OVND although aggregations of inflammatory cells remained. Proliferating cell nuclear antigen (PCNA), cytokeratin 19 (CK19), and cancer antigen (CA19-9) staining were strongly positive in OVND, but were only slight in OVNDAs. Moreover, OVNDAsPz, appeared a few inflammatory infiltrations, bile duct proliferation, fibrosis and CCA area than the OVNDAs group. Thirty seven point five percent of hamster in this group could not develop CCA. These findings suggest that using aspirin combination with praziquantel treatment can improve the hepatobiliary system after O. viverrini infection and reduce the risk of CCA. PMID- 26277609 TI - Complex Rotation Quantum Dynamic Neural Networks (CRQDNN) using Complex Quantum Neuron (CQN): Applications to time series prediction. AB - Quantum Neural Networks (QNN) models have attracted great attention since it innovates a new neural computing manner based on quantum entanglement. However, the existing QNN models are mainly based on the real quantum operations, and the potential of quantum entanglement is not fully exploited. In this paper, we proposes a novel quantum neuron model called Complex Quantum Neuron (CQN) that realizes a deep quantum entanglement. Also, a novel hybrid networks model Complex Rotation Quantum Dynamic Neural Networks (CRQDNN) is proposed based on Complex Quantum Neuron (CQN). CRQDNN is a three layer model with both CQN and classical neurons. An infinite impulse response (IIR) filter is embedded in the Networks model to enable the memory function to process time series inputs. The Levenberg Marquardt (LM) algorithm is used for fast parameter learning. The networks model is developed to conduct time series predictions. Two application studies are done in this paper, including the chaotic time series prediction and electronic remaining useful life (RUL) prediction. PMID- 26277610 TI - Multistability of memristive Cohen-Grossberg neural networks with non-monotonic piecewise linear activation functions and time-varying delays. AB - The problem of coexistence and dynamical behaviors of multiple equilibrium points is addressed for a class of memristive Cohen-Grossberg neural networks with non monotonic piecewise linear activation functions and time-varying delays. By virtue of the fixed point theorem, nonsmooth analysis theory and other analytical tools, some sufficient conditions are established to guarantee that such n dimensional memristive Cohen-Grossberg neural networks can have 5(n) equilibrium points, among which 3(n) equilibrium points are locally exponentially stable. It is shown that greater storage capacity can be achieved by neural networks with the non-monotonic activation functions introduced herein than the ones with Mexican-hat-type activation function. In addition, unlike most existing multistability results of neural networks with monotonic activation functions, those obtained 3(n) locally stable equilibrium points are located both in saturated regions and unsaturated regions. The theoretical findings are verified by an illustrative example with computer simulations. PMID- 26277611 TI - From principles to practice: Description of a novel equity-based HCV primary care treatment model for PWID. AB - BACKGROUND: Knowledge is increasing regarding effective models of HCV care for people who inject drugs (PWID). However, examples implementing such models in primary care are lacking, leaving a gap in our applied understanding of how practically we best scale-up such care: this is critical and urgent if the benefits of treatment advances are to be realized for PWID. A CASE STUDY: The Cool Aid Community Health Centre (CHC) provides HCV programming for PWID, putting recent advances into practice. A case study of the CHC's HCV programming describes the practice experience and outcomes of its novel, multidisciplinary, primary care, inner-city HCV treatment program for PWID. This paper describes how this model of care functions to address the many barriers to treatment and successfully facilitate adherence to treatment. CONCLUSION: Medical advances for HCV will be ineffectual without effective management of complex barriers to care related to substance use, mental health, trauma, poverty, homelessness, criminalization, cultural issues, stigma and marginalization. HCV treatment for PWIDs benefits from low-threshold settings which are culturally appropriate and where trusting relationships between clients and providers are nurtured. Public investment in primary care treatment for PWID living with HCV, including investments in supports that address the social barriers faced by these vulnerable populations would build on existing evidence and improve HCV outcomes for PWID. PMID- 26277613 TI - A Novel Anti-classification Approach for Knowledge Protection. AB - Classification is the problem of identifying a set of categories where new data belong, on the basis of a set of training data whose category membership is known. Its application is wide-spread, such as the medical science domain. The issue of the classification knowledge protection has been paid attention increasingly in recent years because of the popularity of cloud environments. In the paper, we propose a Shaking Sorted-Sampling (triple-S) algorithm for protecting the classification knowledge of a dataset. The triple-S algorithm sorts the data of an original dataset according to the projection results of the principal components analysis so that the features of the adjacent data are similar. Then, we generate noise data with incorrect classes and add those data to the original dataset. In addition, we develop an effective positioning strategy, determining the added positions of noise data in the original dataset, to ensure the restoration of the original dataset after removing those noise data. The experimental results show that the disturbance effect of the triple-S algorithm on the CLC, MySVM, and LibSVM classifiers increases when the noise data ratio increases. In addition, compared with existing methods, the disturbance effect of the triple-S algorithm is more significant on MySVM and LibSVM when a certain amount of the noise data added to the original dataset is reached. PMID- 26277612 TI - Hypoxia-Inducible Factor alpha and Hif-prolyl Hydroxylase Characterization and Gene Expression in Short-Time Air-Exposed Mytilus galloprovincialis. AB - Aquatic organisms experience environmental hypoxia as a result of eutrophication and naturally occurring tidal cycles. Mytilus galloprovincialis, being an anoxic/hypoxic-tolerant bivalve, provides an excellent model to investigate the molecular mechanisms regulating oxygen sensing. Across the animal kingdom, inadequacy in oxygen supply is signalled predominantly by hypoxia-inducible factors (HIF) and Hif-prolyl hydroxylases (PHD). In this study, hif-alpha 5'-end and partial phd mRNA sequences from M. galloprovincialis were obtained. Phylogenetic and molecular characterization of both HIF-alpha and PHD putative proteins showed shared key features with the respective orthologues from animals strongly suggesting their crucial involvement in the highly conserved oxygen sensing pathway. Both transcripts displayed a tissue-specific distribution with prominent expression in gills. Quantitative gene expression analysis of hif-alpha and phd mRNAs from gills of M. galloprovincialis demonstrated that both these key sensors are transcriptionally modulated by oxygen availability during the short time air exposure and subsequent re-oxygenation treatments proving that they are critical players of oxygen-sensing mechanisms in mussels. Remarkably, hif-alpha gene expression showed a prompt and transient response suggesting the precocious implication of this transcription factor in the early phase of the adaptive response to hypoxia in Mytilus. HIF-alpha and PHD proteins were modulated in a time-dependent manner with trends comparable to mRNA expression patterns, thus suggesting a central role of their transcriptional regulation in the hypoxia tolerance strategies in marine bivalves. These results provide molecular information about the effects of oxygen deficiency and identify hypoxia responsive biomarker genes in mussels applicable in ecotoxicological studies of natural marine areas. PMID- 26277614 TI - A Clinical Support System Based on Quality of Life Estimation. AB - Quality of life is a concept influenced by social, economic, psychological, spiritual or medical state factors. More specifically, the perceived quality of an individual's daily life is an assessment of their well-being or lack of it. In this context, information technologies may help on the management of services for healthcare of chronic patients such as estimating the patient quality of life and helping the medical staff to take appropriate measures to increase each patient quality of life. This paper describes a Quality of Life estimation system developed using information technologies and the application of data mining algorithms to access the information of clinical data of patients with cancer from Otorhinolaryngology and Head and Neck services of an oncology institution. The system was evaluated with a sample composed of 3013 patients. The results achieved show that there are variables that may be significant predictors for the Quality of Life of the patient: years of smoking (p value 0.049) and size of the tumor (p value < 0.001). In order to assign the variables to the classification of the quality of life the best accuracy was obtained by applying the John Platt's sequential minimal optimization algorithm for training a support vector classifier. In conclusion data mining techniques allow having access to patients additional information helping the physicians to be able to know the quality of life and produce a well-informed clinical decision. PMID- 26277615 TI - Setting Appropriate Goals for the Next Generation of Clinical Trials in Myelofibrosis. AB - New targeted therapies administered in phase II and phase III studies have produced substantial improvements in outcomes of myelofibrosis (MF). However, strong documentation that the new agents modify the natural history of the disease is lacking, and a number of therapeutic indications of new drugs remain unaddressed. Overall survival (OS) improvement is the major goal of next generation clinical trials in MF. This may be attained if an adequate population of patients and an unambiguous design of the trial will be selected. Another goal is preventing disease progression in early MF: this requires a controlled clinical trial with an accessible endpoint and a clinically relevant definition of disease progression. Improvement in the documentation of responsiveness of patient-reported outcomes (PROs) will allow to use them as a critical endpoint of new trials. Finally, exploiting the clinical utility of biomarkers should become a major goal of future clinical experimentation in MF. PMID- 26277616 TI - Assessing the relationship between oral chronic graft-versus-host disease and global measures of quality of life. AB - OBJECTIVE: Chronic GVHD (cGVHD) is a frequent complication of allogeneic hematopoietic stem cell transplantation (HSCT) and affects multiple organ systems, with the oral cavity being one of the most frequently affected sites. Patients with cGVHD experience reduced quality of life (QOL), yet the specific impact of oral cGVHD on QOL is poorly understood. The objective of this study was to characterize the impact of oral cGVHD on global measures of QOL. MATERIALS AND METHODS: QOL data were collected using the FACT-BMT and SF-36 instruments for 569 patients enrolled in the Chronic GVHD Consortium, with a total of 1915 follow-up visits. At study enrollment, patients were categorized as isolated oral cGVHD (n=22), oral and concomitant extra-oral cGVHD (n=420), and only extra-oral cGVHD (n=127). Utilizing all longitudinal data, QOL scores were compared using a multivariable linear model controlling for demographic, transplant, and cGVHD characteristics. RESULTS: Patients with isolated oral cGVHD reported better physical well-being (P=0.009), BMT well-being (P=0.01), and decreased bodily pain (P=0.01) compared to patients with oral and concomitant extra-oral cGVHD, but the differences in scores did not reach the defined threshold for clinical significance (6 points for FACT-BMT domains and 5 points for SF-36 domains). CONCLUSIONS: Global QOL scores are similar in patients with isolated oral cGVHD and patients with oral and concomitant extra-oral cGVHD. PMID- 26277617 TI - Clinical effect of a positive surgical margin without extraprostatic extension after robot-assisted radical prostatectomy. AB - OBJECTIVES: The aim of this study was to investigate the effect of positive surgical margin (PSM) without extraprostatic extension after robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: We retrospectively reviewed 837 patients who underwent RARP for clinically localized prostate cancer without neoadjuvant endocrine therapy. The pT2+category lesions were defined according to World Health Organization classification. The actuarial probabilities of biochemical recurrence-free survival (BCR-FS) were determined using Kaplan-Meier analysis. Univariate and multivariate Cox proportional hazards regression analyses were also used to identify independent predictors for BCR. RESULTS: Of the 837 patients, 102 (12.2%) experienced BCR during the follow-up period. The BCR-FS rate was significantly higher in patients with pT2+category tumors than in those with pT3a category tumors, and significantly lower in patients with pT2+category tumors than that in those with pT2 category tumors without PSM. The BCR-FS rate of patients with pT2+category tumors was significantly higher than that with pT3a category tumors with PSM but not significantly different from that with pT3a category tumors without PSM. In a multivariate analysis, the pathological T category considering pT2+category was one of independent predictive factors for BCR. CONCLUSIONS: This study support the hypothesis that the pT2+category disease is associated with a significantly increased risk of BCR in patients with organ-confined prostate cancer after RARP. As PSM can be avoided in some cases, urologists should continually seek to improve their operative skills and to reduce the rate of PSM, especially in patients with organ-confined prostate cancer. PMID- 26277618 TI - Asynchrony of senescence among phenotypic traits in a wild mammal population. AB - The degree to which changes in lifespan are coupled to changes in senescence in different physiological systems and phenotypic traits is a central question in biogerontology. It is underpinned by deeper biological questions about whether or not senescence is a synchronised process, or whether levels of synchrony depend on species or environmental context. Understanding how natural selection shapes patterns of synchrony in senescence across physiological systems and phenotypic traits demands the longitudinal study of many phenotypes under natural conditions. Here, we examine the patterns of age-related variation in late adulthood in a wild population of Soay sheep (Ovis aries) that have been the subject of individual-based monitoring for thirty years. We examined twenty different phenotypic traits in both males and females, encompassing vital rates (survival and fecundity), maternal reproductive performance (offspring birth weight, birth date and survival), male rutting behaviour, home range measures, parasite burdens, and body mass. We initially quantified age-related variation in each trait having controlled for annual variation in the environment, among individual variation and selective disappearance effects. We then standardised our age-specific trait means and tested whether age trajectories could be meaningfully grouped according to sex or the type of trait. Whilst most traits showed age-related declines in later life, we found striking levels of asynchrony both within and between the sexes. Of particular note, female fecundity and reproductive performance declined with age, but male annual reproductive success did not. We also discovered that whilst home range size and quality decline with age in females, home range size increases with age in males. Our findings highlight the complexity of phenotypic ageing under natural conditions and, along with emerging data from other wild populations and laboratory models, suggest that the long-standing hypothesis within evolutionary biology that fitness related traits should senesce in a synchronous manner is seriously flawed. PMID- 26277619 TI - The cefazolin inoculum effect in methicillin-susceptible Staphylococcus aureus blood isolates: their association with dysfunctional accessory gene regulator (agr). AB - We evaluated the clinical significance of the cefazolin inoculum effect (CIE) in methicillin-susceptible Staphylococcus aureus (MSSA) isolates. In total, 146 isolates were recovered from patients with MSSA bacteremia at 9 hospitals in Korea. The CIE was observed in 16 MSSA isolates, and while type A was the only detected beta-lactamase in MSSA isolates exhibiting the CIE, no strains expressing type B, C, or D beta-lactamases exhibited this effect. The CIE was only observed in agr group III and I isolates and was significantly more common in isolates with agr dysfunction than in those with functional agr (P<0.001). Even among isolates producing type A beta-lactamase, the CIE was also prevalent in isolates with dysfunctional agr than in isolates with functional agr (P=0.025). This study demonstrates an association between the CIE of MSSA isolates and agr dysfunction, in addition to those between the CIE and type A beta-lactamase. PMID- 26277620 TI - Antioxidant activity of chemically synthesized AgNPs and biosynthesized Pongamia pinnata leaf extract mediated AgNPs - A comparative study. AB - Biosynthesis of metal nanoparticles is the present research in the limb of nanotechnology which reduces the toxicity of metal nanoparticles. Green chemistry approach emphasizes that the usage of plant material has offered a reliable, simple, nontoxic and eco-friendly that links Nanotechnology and Biotechnology. Increasing environmental concerns over chemical synthesis routes have resulted in attempts to develop bio-mimetic approaches. The current study deals with novel method for biosynthesis of AgNPs using Pongamia pinnata leaf extract as reducing agent. These biosynthesized nanoparticles were characterized with the help of UV vis Spectroscopy, Photoluminescence (PL) and Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Atomic force microscopy (AFM), Dynamic light scattering (DLS) and Zeta Potential (ZP). Free radical scavenging potential of P. pinnata synthesized silver nanoparticles was evaluated in vitro by using five different assays viz., DPPH, ABT+S, Hydroxyl, Superoxide anion and Nitric oxide scavenging assays are also adopted. Capping of AgNPs by various polyphenolic compounds present in P. pinnata leaf extract appears to be a major contributor to lower toxicity compared to chemically synthesized AgNPs. The surface plasmon resonance shows 425nm and grain size of the AgNPs was measured from XRD and FTIR revealed the bioconjucation of AgNPs. The in vitro antioxidant activity of AgNPs showed a significant effect on scavenging of free radicals. The results suggest that the silver nanoparticles from P. pinnata can be potent natural antioxidants and can be essential for health preservation against oxidative stress related degenerative diseases, such as cancer. The vitality of this study lies in the formation of silver nanoparticles by utilizing the wealth of global ecological resources, eliminating obnoxious and toxic reagents which are hazardous to be handled as well as to be applied. PMID- 26277621 TI - Changes in microRNA expression during differentiation of embryonic and induced pluripotent stem cells to definitive endoderm. AB - Pluripotent stem cells, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have the potential to treat type 1 diabetes through cell replacement therapy. However, the protocols used to generate insulin expressing cells in vitro frequently result in cells which have an immature phenotype and are functionally restricted. MicroRNAs (miRNAs) are now known to be important in cell fate specification, and a unique miRNA signature characterises pancreatic development at the definitive endoderm stage. Several studies have described differences in miRNA expression between ESCs and iPSCs. Here we have used microarray analysis both to identify miRNAs up- or down-regulated upon endoderm formation, and also miRNAs differentially expressed between ESCs and iPSCs. Several miRNAs fulfilling both these criteria were identified, suggesting that differences in the expression of these miRNAs may affect the ability of pluripotent stem cells to differentiate into definitive endoderm. The expression of these miRNAs was validated by qRT-PCR, and the relationship between one of these miRNAs, miR-151a-5p, and its predicted target gene, SOX17, was investigated by luciferase assay, and suggested an interaction between miR-151a-5p and this key transcription factor. In conclusion, these findings demonstrate a unique miRNA expression pattern for definitive endoderm derived from both embryonic and induced pluripotent stem cells. PMID- 26277622 TI - BTLA expression declines on B cells of the aged and is associated with low responsiveness to the trivalent influenza vaccine. AB - Virus-neutralizing antibody and B cell responses to influenza A viruses were measured in 35 aged and 28 middle-aged individuals following vaccination with the 2012 and 2013 trivalent inactivated influenza vaccines. Antibody responses to the vaccine strains were lower in the aged. An analysis of B cell subsets by flow cytometry with stains for immunoregulators showed that B cells of multiple subsets from the aged as compared to younger human subjects showed differences in the expression of the co-inhibitor B and T lymphocyte attenuator (BTLA). Expression of BTLA inversely correlated with age and appears to be linked to shifting the nature of the response from IgM to IgG. High BTLA expression on mature B cells was linked to higher IgG responses to the H1N1 virus. Finally, high BTLA expression on isotype switched memory B cells was linked to better preservation of virus neutralizing antibody titers and improved recall responses to vaccination given the following year. PMID- 26277624 TI - Analysis of a FANCE Splice Isoform in Regard to DNA Repair. AB - The FANC-BRCA DNA repair pathway is activated in response to interstrand crosslinks formed in DNA. A homozygous mutation in 1 of the 17 Fanconi anemia (FA) genes results in malfunctions of this pathway and development of FA syndrome. The integrity of this protein network is essential for good maintenance of DNA repair process and genome stability. Following the identification of an alternatively splice isoform of FANCE (Fanconi anemia complementation group E) significantly expressed in breast cancer individuals from high-risk non-BRCA1/2 families, we studied the impact of this FANCE splice isoform (FANCEDelta4) on DNA repair processes. We have demonstrated that FANCEDelta4 mRNA was efficiently translated into a functional protein and expressed in normal and breast cancer cell lines. Following treatment with the crosslinking agent mitomycin C, EUFA130 (FANCE-deficient) cells infected with FANCEDelta4 were blocked into G2/M phase, while cell survival was significantly reduced compared with FANCE-infected EUFA130 cells. In addition, FANCEDelta4 did not allow FANCD2 and FANCI monoubiquitination, which represents a crucial step of the FANC-BRCA functional pathway. As observed for FANCE wild-type protein, localization of FANCEDelta4 protein was confined to the nucleus following mitomycin C treatment. Although FANCEDelta4 protein showed interaction with FANCE, FANCEDelta4 did not support normal function of FANCE protein in this pathway and could have deleterious effects on FANCE protein activity. We have demonstrated that FANCEDelta4 seems to act as a regulator of FANCD2 protein expression level by promoting its degradation. This study highlights the importance of an efficient regulation of alternative splicing expression of FA genes for proper DNA repair. PMID- 26277625 TI - Demographic and behavioural correlates of six sexting behaviours among Australian secondary school students. AB - Background There has been increasing attention on assessing rates of sexting in adolescents and of the potential negative effects of the behaviour. Our aim was to assess rates and correlates of sexting in Australian students in years10, 11 and 12. METHODS: The current study was part of The Fifth National Survey of Australian Secondary Students and Sexual Health and reports on responses of 2114 students (811 male, 1303 female). Sexting was assessed using six items: sending a sexually explicit written text message; receiving a sexually explicit text message; sending a sexually explicit nude or nearly nude photo or video of themselves; sending a sexually explicit nude or nearly nude photo or video of someone else; receiving a sexually explicit nude or nearly nude photo or video of someone else; and using a social media site for sexual reasons. RESULTS: Approximately half of the students had received (54%, 1139/2097) or sent (43%, 904/2107) a sexually explicit written text message. Sexually explicit images had been received by 42% (880/2098) of students, one in four students had sent a sexually explicit image of themselves (26%, 545/2102) and one in 10 had sent a sexually explicit image of someone else (9%, 180/2095). Finally, 22% (454/2103) of students had used social media for sexual reasons. Sexting was associated with several correlates. CONCLUSIONS: Sexting was relatively common in this sample of year 10, 11 and 12 Australian students, particularly among older students, those who are sexually active, and those who use recreational substances. PMID- 26277623 TI - Shelter in a Swarm. AB - Flagella propel bacteria during both swimming and swarming, dispersing them widely. However, while swimming bacteria use chemotaxis to find nutrients and avoid toxic environments, swarming bacteria appear to suppress chemotaxis and to use the dynamics of their collective motion to continuously expand and acquire new territory, barrel through lethal chemicals in their path, carry along bacterial and fungal cargo that assists in exploration of new niches, and engage in group warfare for niche dominance. Here, we focus on two aspects of swarming, which, if understood, hold the promise of revealing new insights into microbial signaling and behavior, with ramifications beyond bacterial swarming. These are as follows: how bacteria sense they are on a surface and turn on programs that promote movement and how they override scarcity and adversity as dense packs. PMID- 26277626 TI - Silver and titanium dioxide nanoparticles alter oxidative/inflammatory response and renin-angiotensin system in brain. AB - The study was designed to examine the effects of silver AgNPs, 20 nm) and titanium dioxide (Aeroxide((r)) P25 TiO2NPs, 21 nm) nanoparticles on brain oxidative stress parameters, its antioxidant potential and brain renin angiotensin system (RAS) in vivo. The analysis was performed 28 days after single dose injection of TiO2NPs and AgNPs (10 or 5 mg/kg body weight, respectively). The AgNPs, but not TiO2NPs, administration resulted in decreased lipid and cholesterol peroxidation. Antioxidant enzymes gene expression and/or activity were changed differently for TiO2NPs and AgNPs group. The TiO2NPs decreased aromatase gene expression, and glutathione peroxidase and reductase activities. In AgNPs group the sodium dismutase 1 and glutathione reductase mRNA levels were decreased as opposed to their activities. Both NPs altered the expression of brain RAS genes (angiotensinogen, renin, angiotensin I converting enzyme 1 and 2), but only TiO2NPs caused similar changes on protein level. The expression of amyloid beta precursor protein gene was not altered by any kind of injected NPs. The TiO2NPs were more potent modulator of gene expression in the brain than AgNPs, despite the two times lower dosage. These results suggest that AgNPs and TiO2NPs exposure may modulate the brain function, but with different strength. PMID- 26277627 TI - Degradation and detection of transgenic Bacillus thuringiensis DNA and proteins in flour of three genetically modified rice events submitted to a set of thermal processes. AB - This study aimed to investigate the degradation of three transgenic Bacillus thuringiensis (Bt) genes (Cry1Ab, Cry1Ac, and Cry1Ab/Ac) and the corresponding encoded Bt proteins in KMD1, KF6, and TT51-1 rice powder, respectively, following autoclaving, cooking, baking, or microwaving. Exogenous Bt genes were more stable than the endogenous sucrose phosphate synthase (SPS) gene, and short DNA fragments were detected more frequently than long DNA fragments in both the Bt and SPS genes. Autoclaving, cooking (boiling in water, 30 min), and baking (200 degrees C, 30 min) induced the most severe Bt protein degradation effects, and Cry1Ab protein was more stable than Cry1Ac and Cry1Ab/Ac protein, which was further confirmed by baking samples at 180 degrees C for different periods of time. Microwaving induced mild degradation of the Bt and SPS genes, and Bt proteins, whereas baking (180 degrees C, 15 min), cooking and autoclaving led to further degradation, and baking (200 degrees C, 30 min) induced the most severe degradation. The findings of the study indicated that degradation of the Bt genes and proteins somewhat correlated with the treatment intensity. Polymerase chain reaction, enzyme-linked immunosorbent assay, and lateral flow tests were used to detect the corresponding transgenic components. Strategies for detecting transgenic ingredients in highly processed foods are discussed. PMID- 26277628 TI - Invited review: Diagnosis of zearalenone (ZEN) exposure of farm animals and transfer of its residues into edible tissues (carry over). AB - The aim of the review was to evaluate the opportunities for diagnosing the zearalenone (ZEN) exposure and intoxication of farm animals by analyzing biological specimens for ZEN residue levels. Metabolism is discussed to be important when evaluating species-specific consequences for the overall toxicity of ZEN. Besides these toxicological facts, analytics of ZEN residues in various animal-derived matrices requires sensitive, matrix-adapted multi-methods with low limits of quantification, which is more challenging than the ZEN analysis in feed. Based on dose-response experiments with farm animals, the principle usability of various specimens as bio-indicators for ZEN exposure is discussed with regard to individual variation and practicability for the veterinary practitioner. ZEN residue analysis in biological samples does not only enable evaluation of ZEN exposure but also allows the risk for the consumer arising from contaminated foodstuffs of animal origin to be assessed. It was compiled from literature that the tolerable daily intake of 0.25 MUg ZEN/kg body weight and day is exploited to approximately 8%, when a daily basket of animal foodstuffs and associated carry over factors are assumed at reported ZEN contamination levels of complete feed. PMID- 26277629 TI - Antifungal activity of nano and micro charcoal particle polymers against Paecilomyces variotii, Trichoderma virens and Chaetomium globosum. AB - This study investigates the antifungal activity of a polymer integrated with nano porous charcoal particles against Paecilomyces variotii, Chaetomium globosum, Trichoderma virens, which are all filamentous fungi. The charcoal polymers were prepared by combining charcoal powders with plastic resin under a vacuum to form charcoal particle protrusions on the polymer surface. The mycelial growth of P. variotii and T. virens exhibited a reduction of 10 and 30%, respectively, after the conidia were pre-treated with charcoal polymers, and in particular, no mycelial growth was found in C. globosum during 5 days of culture. The adsorption of Ca(2+) into charcoal was suggested to inhibit growth due to the reduction in the flux of calcium ions (Ca(2+)) into the hyphae. In 5 h, about 15 mM of Ca(2+) were removed from CaCl2 solution with 0.2 g/mL of polymers, and the nano-sized pores of the charcoals on the polymer were responsible for the Ca(2+) adsorption. PMID- 26277630 TI - Immunohistopathological analysis of frizzled-4-positive immature melanocytes from hair follicles of patients with Rhododenol-induced leukoderma. PMID- 26277631 TI - Valvular endothelial cells: guardians or destroyers of aortic valve integrity? PMID- 26277632 TI - Lipoprotein particle subclass profiles among metabolically healthy and unhealthy obese and non-obese adults: does size matter? AB - OBJECTIVES: No data regards lipoprotein particle profiles in obese and non-obese metabolic health subtypes exist. We characterised lipoprotein size, particle and subclass concentrations among metabolically healthy and unhealthy obese and non obese adults. METHODS: Cross-sectional sample of 1834 middle-aged Irish adults were classified as obese (BMI >=30 kg/m(2)) and non-obese (BMI <30 kg/m(2)). Metabolic health was defined using three metabolic health definitions based on various cardiometabolic abnormalities including metabolic syndrome criteria, insulin resistance and inflammation. Lipoprotein size, particle and subclass concentrations were determined using nuclear magnetic resonance (NMR) spectroscopy. RESULTS: Lipoprotein profiling identified a range of adverse phenotypes among the metabolically unhealthy individuals, regardless of BMI and metabolic health definition, including increased numbers of small low density lipoprotein (LDL) (P < 0.001) and high density lipoprotein (HDL) particles (P < 0.001), large very low density lipoprotein (VLDL) particles (P < 0.001) and greater lipoprotein related insulin resistance (P < 0.001). The most significant predictors of metabolic health were lower numbers of large VLDL (ORs 2.72-3.13 and 2.49-3.86, P < 0.05 among obese and non-obese individuals, respectively) and small dense LDL particles (ORs 1.78-2.39 and 1.50-1.94, P < 0.05) and higher numbers of large LDL (ORs 1.82-2.66 and 2.84-3.27, P < 0.05) and large HDL particles (ORs 1.88-2.58 and 1.81-3.49, P < 0.05). CONCLUSIONS: Metabolically healthy adults displayed favourable lipoprotein particle profiles, irrespective of BMI and metabolic health definition. These findings underscore the importance of maintaining a healthy lipid profile in the context of overall cardiometabolic health. PMID- 26277633 TI - The influence of housing characteristics on leisure-time sitting. A prospective cohort study in Danish adults. AB - OBJECTIVE: Built environmental attributes have been studied in relation to domestic time spent sedentary. An indoor behaviour has thus been linked to an outdoor setting. Yet, attributes of the actual domestic environment may also influence the time spent sedentary at home. Therefore, the aim was to examine if housing characteristics were cross-sectionally and prospectively related to leisure-time sitting in adults. METHODS: In the Danish Health2006 cohort, 2308 adults were followed for 5 years. At baseline, subjects self-reported housing characteristics (habitat type, habitat surface area and household size), moderate to-vigorous physical activity (MVPA) and socio-demographic factors. Leisure-time sitting was self-reported at baseline and 5-year follow-up. Multiple linear regression was used to assess cross-sectional and prospective associations. RESULTS: At baseline habitat surface area and household size were inversely associated with leisure-time sitting (p<0.01). Living in an apartment was associated with higher leisure-time sitting compared to living in a house (p<0.01). Household size was a predictor of 5-year leisure-time sitting (p<0.01), after adjustment for confounders and the other housing characteristics. CONCLUSIONS: Habitat type, habitat surface area and household size were associated with leisure-time sitting in adults, while especially household size was a predictor of leisure-time sitting five years later. The findings highlight the importance of home-environmental attributes when targeting a reduction in sedentary behaviours. PMID- 26277634 TI - False-normal vitamin B12 results in a patient with pernicious anaemia. AB - Pernicious anaemia is a common autoimmune disorder with a prevalence of approximately 4% amongst Europeans. If untreated, it can result in permanent neurological disability or death. Central to the diagnosis is establishing the presence of vitamin B12 deficiency. Concern has been raised recently regarding false-normal results obtained with competitive-binding vitamin B12 assays performed on automated biochemistry platforms in patients with pernicious anaemia due to the presence of interfering anti-intrinsic factor antibodies in the patient sample. We report a case in which diagnosis of pernicious anaemia was delayed due to false-normal vitamin B12 results. Questioning the results in light of high pre-test probability, and knowledge of the role of functional markers of vitamin B12 deficiency enabled the correct diagnosis to be made so that effective treatment could be initiated. It is crucial that those who frequently request vitamin B12 are aware of the potential problems with the available assays and how these problems can be addressed. We suggest that all patients with normal vitamin B12 levels where there is a high clinical suspicion for deficiency such as a macrocytic anaemia, neurological symptoms or megaloblastic bone marrow should have a functional assay of vitamin B12 (plasma homocysteine or methylmalonic acid) checked to further investigate for vitamin B12 deficiency. PMID- 26277635 TI - Utilization of cardiac troponin assays in adult and pediatric populations: Guideline recommendations vs. reality. AB - OBJECTIVES: We hypothesized significant gaps remained for cardiac troponin (cTn) utilization in the United States, despite an emerging evidence base and guideline recommendations. We tested this hypothesis and investigated differences and trends between the use of cTn in adult versus pediatric hospitals. DESIGN AND METHODS: Individuals were identified by a targeted distribution through personal contact and professional society email lists. Participants completed an online survey (Qualtrics) from 07/15/13 to 07/26/13. The 31-item questionnaire used skipped logic and collected data about the respondent and their institutional cTn clinical practices. Data tabulation and analysis were conducted using Qualtrics and Microsoft Excel. RESULTS: A total of 159 unique laboratories responded to the survey, representing primarily adult (81%) versus pediatric (19%) institutions. 59% of laboratories utilize the guideline recommended 99th percentile as the upper reference limit (URL) for cTn, with large variability in reporting practices among users of the same assay. 73% of laboratories reported simultaneous ordering of other cardiac biomarkers with cTn, a majority which included CK-MB. Interpretive comments were used with cTn in 71 laboratories with a significant amount of heterogeneity. Pediatric hospitals reported a lower frequency of cTn orders and were less likely to consider elevated cTn a critical value. CONCLUSIONS: Gaps in current utilization and reporting of cTn exist, along with practices inconsistent with clinical guideline recommendations. Implementation of the 99th percentile and serial sampling protocols will be critical to adoption of high-sensitivity cTn assays. Differences in chest pain etiology are the most likely reason for the notable differences between cTn use in adults versus pediatric hospitals. PMID- 26277636 TI - Soluble ST2 and galectin-3 in pediatric patients without heart failure. AB - OBJECTIVES: Soluble ST2 (ST2) and galectin-3 (Gal3) are biomarkers of myocardial fibrosis and remodeling. This study provides a foundation for the use of ST2 and Gal3 in pediatric patients by assessing values of these biomarkers among children without heart failure. DESIGN AND METHODS: Sera from 240 children, 40 males and 40 females from each of three age groups, (2-6 years, 7-11 years, and 12-17 years) without heart failure were identified from residual clinical testing. Serum ST2 and Gal3 were measured by ELISA. RESULTS: Serum ST2 increased with age among males, but not females. However, the difference was not statistically significant at the 95th or 97.5th percentiles. No relationship was found between serum Gal3 concentrations and age or gender. Central 95th percentiles (2.5th to 97.5th) were 9-50 ng/mL for ST2 and 7-33 ng/mL for Gal3. CONCLUSIONS: We have presented baseline, normative data for ST2 and Gal3 in children. This will allow for study of the utility of these biomarkers in children with heart disease. PMID- 26277637 TI - Nanoparticles enhance the ability of human neutrophils to exert phagocytosis by a Syk-dependent mechanism. AB - BACKGROUND: Some reports indicate that NPs are ingested by cells via different mechanisms, including phagocytosis. In contrast, the direct role of NPs on the phagocytic process is not well documented. The aim of this study was to determine if titanium dioxide (TiO(2)), zinc oxide (ZnO) and cerium dioxide (CeO(2)) NPs, could alter the ability of neutrophils to exert phagocytosis. METHODS: Freshly isolated human neutrophils were incubated with NPs and their ability to phagocytose opsonized sheep red blood cells (SRBCs) or fluorescent latex beads (LBs) was assessed by optical and fluorescence microscopy, respectively. Syk activation was assessed by western blot experiments and a pharmacological approach with piceatannol, a Syk inhibitor, was used to determine its role in NPs induced neutrophils. The cytokine granulocyte macrophage-colony stimulating factor (GM-CSF) was used as a positive control. RESULTS: All tested NPs enhanced the ability of neutrophil to phagocytose SRBCs and LBs. Syk was activated in NPs induced neutrophils as evidenced by its increased tyrosine phosphorylation level vs controls and the ability of NPs-induced phagocytosis was reversed by piceatannol. CONCLUSIONS: We found that the tested NPs enhanced phagocytosis, although at different degree, and this occurred by a Syk-dependent mechanism. GENERAL SIGNIFICANCE: This is the first study demonstrating that NPs, by themselves, can directly enhance FcR-mediated (opsonized SRBCs) and complement mediated (LBs) phagocytosis. Moreover, as part of their mode of action, we determined that NPs can act similarly to GM-CSF leading to Syk activation involved in phagocytosis. This has to be taken under consideration for future nanobiology and nanomedicine studies. PMID- 26277638 TI - Modelling microbial health risk of wastewater reuse: A systems perspective. AB - There is a widespread need for the use of quantitative microbial risk assessment (QMRA) to determine reclaimed water quality for specific uses, however neither faecal indicator levels nor pathogen concentrations alone are adequate for assessing exposure health risk. The aim of this study was to build a conceptual model representing factors contributing to the microbiological health risks of reusing water treated in maturation ponds. This paper describes the development of an unparameterised model that provides a visual representation of theoretical constructs and variables of interest. Information was collected from the peer reviewed literature and through consultation with experts from regulatory authorities and academic disciplines. In this paper we explore how, considering microbial risk as a modular system, following the QMRA framework enables incorporation of the many factors influencing human exposure and dose response, to better characterise likely human health impacts. By using and expanding upon the QMRA framework we deliver new insights into this important field of environmental exposures. We present a conceptual model of health risk of microbial exposure which can be used for maturation ponds and, more importantly, as a generic tool to assess health risk in diverse wastewater reuse scenarios. PMID- 26277639 TI - Occurrence, fate and ecological risk of five typical azole fungicides as therapeutic and personal care products in the environment: A review. AB - Azole fungicides are widely used to treat fungal infection in human. After application, these chemicals may reach to the receiving environment via direct or indirect discharge of wastewaters, thus posing potential risks to non-target organisms. We aimed to review the occurrence, fate and toxicological effects of some representative household azole fungicides in the environment. Azole fungicides were widely detected in surface water and sediment of the aquatic environment due to their incomplete removal in wastewater treatment plants. These chemicals are found resistant to microbial degradation, but can undergo photolysis under UV irradiation. Due to different physiochemical properties, azole fungicides showed different environmental behaviors. The residues of azole fungicides could cause toxic effects on aquatic organisms such as algae and fish. The reported effects include regulation changes in expression of cytochrome P450 related genes and alteration in CYP450-regulated steroidogenesis causing endocrine disruption in fish. Further studies are essential to investigate the removal of azole fungicides by advanced treatment technologies, environmental fate such as natural photolysis, and toxic pathways in aquatic organisms. PMID- 26277640 TI - Interactions between nuclear genes and a foreign mitochondrial genome in the redbelly dace Chrosomus eos. AB - Given the coevolution process occurring between nuclear and mitochondrial genomes, the effects of introgressive hybridization remain puzzling. In this study, we take advantage of the natural co-occurrence of two biotypes bearing a similar nuclear genome (Chrosomus eos) but harbouring mitochondria from different species (wild type: C. eos; cybrids: Chrosomus neogaeus) to determine the extent of phenotype changes linked to divergence in the mitochondrial genome. Changes were assessed through differences in gene expression, enzymatic activity, proteomic and swimming activity. Our data demonstrate that complex IV activity was significantly higher in cybrids compared to wild type. This difference could result from one variable amino acid on the COX3 mitochondrial subunit and/or from a tremendous change in the proteome. We also show that cybrids present a higher swimming performance than wild type. Ultimately, our results demonstrate that the absence of coevolution for a period of almost ten million years between nuclear and mitochondrial genomes does not appear to be necessarily deleterious but could even have beneficial effects. Indeed, the capture of foreign mitochondria could be an efficient way to circumvent the selection process of genomic coevolution, allowing the rapid accumulation of new mutations in C. eos cybrids. PMID- 26277641 TI - Effect of endoscopic third ventriculostomy on cerebrospinal fluid pressure in the cerebral ventricles. AB - We aimed to show how endoscopic third ventriculostomy (ETV) treatment may affect cerebrospinal fluid (CSF) flow dynamics in hydrocephalus, with and without aqueductal stenosis. Hydrocephalus is a neurological disorder which is characterized by enlarged brain ventricles. The periodic motion of CSF flow as a function of the cardiac cycle was prescribed as the inlet boundary condition at the foramen of Monro, and ETV was modeled as a 5mm diameter hole in the anterior wall of the third ventricle. The results show that ETV reduces the pressure in the ventricles by nine-fold in the model with aqueductal stenosis, and three-fold in the model without aqueductal stenosis. More importantly, ETV changes the temporal characteristics of the CSF pressure waveform in the model without aqueductal stenosis, such that there is higher pressure in the ventricle during diastole. This study suggests that changes in the temporal characteristics of the CSF pressure waveform in the ventricles may be the reason why ETV treatment is not effective for hydrocephalus without aqueductal stenosis. PMID- 26277642 TI - Current indications for the surgical treatment of prolactinomas. AB - The purpose of this study was to examine the current indications for transsphenoidal surgery in the prolactinoma patient population, and to determine the outcomes of patients who undergo such operations. Transsphenoidal surgery may be indicated in prolactinoma patients who are resistant and/or intolerant to dopamine agonist (DA) therapy. We performed a retrospective review of the medical records of prolactinoma patients over a 6 year period (April 2008 to April 2014) at a large volume academic center. The median follow-up time was 12.0 months (range: 3-69). All patients who were included in the study (n=66) were treated with DA therapy and subsequently underwent an endonasal transsphenoidal operation. Of the 66 patients, 44 were women (mean age 34.2 years) and 22 were men (mean 41.7 years). There were 29 (43.9%) intolerant patients and 29 (43.9%) resistant patients. Postoperatively, 18 intolerant patients (66.7%) had normalized prolactin levels without the need for DA therapy, and five (17.2%) required DA to normalize their prolactin levels (p=0.02). Six patients (20.6%) had persistently elevated prolactin levels but were no longer receiving DA treatment (p<0.001). Postoperatively, 10 resistant patients (35.7%) had normal prolactin levels without DA therapy, and seven patients (25%) were treated with DA therapy to normalize their prolactin levels (p=0.22). Eight patients (28.6%) had supraphysiologic prolactin levels but were no longer taking a DA (p<0.001). Three patients (10.7%) were hyperprolactinemic, despite postoperative treatment with DA (p<0.001). After an appropriate treatment interval with multiple DA, radiographic follow-up, and careful clinical evaluation, prolactinoma patients can be offered surgery as an effective therapeutic option. PMID- 26277643 TI - Pain Catastrophizing and Fear of Pain Predict the Experience of Pain in Body Parts Not Targeted by a Delayed-Onset Muscle Soreness Procedure. AB - The present study examined whether pain catastrophizing and pain-related fear predict the experience of pain in body regions that are not targeted by an experimental muscle injury protocol. A delayed-onset muscle soreness (DOMS) protocol was used to induce pain unilaterally in the pectoralis, serratus, trapezius, latissimus dorsi, and deltoid muscles. The day after the DOMS protocol, participants were asked to rate their pain as they lifted weighted canisters with their targeted (ie, injured) arm and their nontargeted arm. The lifting task is a nonnoxious stimulus unless participants are already experiencing musculoskeletal pain. Therefore, reports of pain on the nontargeted arm were operationalized as pain in response to a nonnoxious stimulus. Eighty-two healthy university students (54 men, 28 women) completed questionnaires on pain catastrophizing and fear of pain and went through the DOMS protocol. The analyses revealed that catastrophizing and pain-related fear prospectively predicted pain experience in response to a nonnoxious stimulus. The possible mechanisms underlying this effect and clinical implications are discussed. PERSPECTIVE: Pain catastrophizing and fear of pain prospectively predict the pain experience in response to a nonnoxious stimulus. The pattern of findings is consistent with the predictions of current models of generalization of pain-related fear. PMID- 26277644 TI - Transpulmonary radiofrequency ablation of hepatocellular carcinoma contiguous to the heart. PMID- 26277645 TI - Uterine remnant: An uncommon finding after transvaginal hysterectomy. PMID- 26277646 TI - 'Smartening' anticancer therapeutic nanosystems using biomolecules. AB - To be effective, anticancer agents must induce cell killing in a selective manner, something that is proving difficult to achieve. Drug delivery systems could help to solve problems associated with the lack of selectivity of classical chemotherapeutic agents. However, to realize this, such systems must overcome multiple physiological barriers. For instance, they must evade surveillance by the immune system, attach selectively to target cells, and gain access to their interior. Furthermore, there they must escape endosomal entrapment, and release their cargoes in a controlled manner, without affecting their functionality. Here we review recent efforts aiming at using biomolecules to confer these abilities to bare nanoparticles, to transform them into smart anticancer therapeutic nanosystems. PMID- 26277647 TI - Investigating the potential immune role of fish NCAMs: Molecular cloning and expression analysis in mandarin fish. AB - The immune role of NCAMs has been revealed in mammals, yet there is no such report in fish. Hence, we analyzed the molecular characterizations and immune associated expression patterns of NCAMs in mandarin fish. Three NCAM members, named mfNCAM1a, mfNCAM1b and mfNCAM2, were identified. Among the cDNA sequences of mfNCAMs, AU-rich elements in the 3' UTRs of mfNCAM1b and mfNCAM2 as well as VASE sequences in the fourth Ig-like domain-encoding regions of mfNCAM1a and mfNCAM1b were discovered. Moreover, the syntenic analysis suggested that the duplication of NCAM1 is fish-specific. At mRNA and protein levels, the expression analyses revealed that mfNCAMs existed in both systemic and mucosal immune tissues, and located within lymphoid cells. Upon stimulated either by LPS or poly I:C, the expression level of mfNCAM1a was significantly up-regulated in head kidney, spleen, liver, and gut, whereas mfNCAM1b only in head kidney and liver, and mfNCAM2 only in liver. Additionally, the cells coexpressed mfNCAM1 and mfNCCRP-1 might imply the equivalents to mammalian NK cells. Our finding firstly demonstrates the member-specific immune-related tissue expression pattern and immune activity for fish NCAMs. Current data indicate that mfNCAM2 has little immune activity, while the immune activity of mfNCAM1a exists in more tissues than mfNCAM1b, and mfNCAM1a may tend to respond more actively to viral while mfNCAM1b to bacterial stimulants. Additionally, NCAM1b should be a fish-specific member with unique immune function, judging from its different expression pattern, immune activity as well as phylogenetic relationship to mfNCAM1a. PMID- 26277648 TI - Influences of binding to dissolved organic matter on hydrophobic organic compounds in a multi-contaminant system: Coefficients, mechanisms and ecological risks. AB - The complexation flocculation (CF) method was successfully employed to identify binding coefficients (Kdoc) of specific organic contaminants to dissolved organic matter (DOM, often indicated by dissolved organic carbon, DOC) in a multi contaminant hydrophobic organic contaminant (HOC) system. Kdoc values were obtained for most of the evaluated 33 HOCs, indicating the feasibility and applicability of the CF method in a multi-contaminant system. Significant positive correlations were observed between binding coefficients and octanol water partition coefficients (Kow) for organic halogen compounds, such as polybrominated diphenyl ethers (PBDEs) (R(2) = 0.95, p < 0.05) and organic chlorine pesticides (OCPs) (methoxychlor excluded, R(2) = 0.82, p < 0.05). The positive correlations identified between the lgKdoc and lgBCF (bioconcentration factor) for PBDEs and OCPs, as well as the negative correlation observed for polycyclic aromatic hydrocarbons (PAHs), indicated that different binding or partition mechanisms between PAHs and organic halogen compounds exist. These differences further result in discriminative competition partitions of HOCs between DOM and organisms. Assuming that only freely dissolved HOCs are bioconcentrative, the results of DOM-influenced bioconcentration factor (BCFDOM) and DOM-influenced lowest observed effect level (LOELDOM) indicate that the ecological risk of HOCs is decreased by DOM. PMID- 26277649 TI - Oil sands development and its impact on atmospheric wet deposition of air pollutants to the Athabasca Oil Sands Region, Alberta, Canada. AB - Characterization of air pollutant deposition resulting from Athabasca oil sands development is necessary to assess risk to humans and the environment. To investigate this we collected event-based wet deposition during a pilot study in 2010-2012 at the AMS 6 site 30 km from the nearest upgrading facility in Fort McMurray, AB, Canada. Sulfate, nitrate and ammonium deposition was (kg/ha) 1.96, 1.60 and 1.03, respectively. Trace element pollutant deposition ranged from 2 * 10(-5) - 0.79 and exhibited the trend Hg < Se < As < Cd < Pb < Cu < Zn < S. Crustal element deposition ranged from 1.4 * 10(-4) - 0.46 and had the trend: La < Ce < Sr < Mn < Al < Fe < Mg. S, Se and Hg demonstrated highest median enrichment factors (130-2020) suggesting emissions from oil sands development, urban activities and forest fires were deposited. High deposition of the elements Sr, Mn, Fe and Mg which are tracers for soil and crustal dust implies land clearing, mining and hauling emissions greatly impacted surrounding human settlements and ecosystems. PMID- 26277650 TI - [Intraoperative fluid therapy in infants with congestive heart failure due to intracranial pial arteriovenous fistula]. AB - Pial arteriovenous fistula is a rare intracranial congenital malformation (0.1-1: 100,000). It has a high blood flow between one or more pial arteries and drains into the venous circulation. It is usually diagnosed during the childhood by triggering an intracranial hypertension and/or congestive heart failure due to left-right systemic shunt. It is a rare malformation with a complex pathophysiology. The perioperative anaesthetic management is not well established. We present a 6-month-old infant diagnosed with pial arteriovenous fistula with hypertension and congestive heart failure due to left-right shunt. He required a craniotomy and clipping of vascular malformation. Anaesthetic considerations in patients with this condition are a great challenge. It must be performed by multidisciplinary teams with experience in paediatrics. The maintenance of blood volume during the intraoperative course is very important. Excessive fluid therapy can precipitate a congestive heart failure or intracranial hypertension, and a lower fluid therapy may cause a tissue hypoxia due to the bleeding. PMID- 26277651 TI - Graphene oxide based fluorescence resonance energy transfer and loop-mediated isothermal amplification for white spot syndrome virus detection. AB - Graphene oxide (GO) is attractived for biological or medical applications due to its unique electrical, physical, optical and biological properties. In particular, GO can adsorb DNA via pi-pi stacking or non-covalent interactions, leading to fluorescence quenching phenomenon applicable for bio-molecular detection. In this work, a new method for white spot syndrome virus (WSSV)-DNA detection is developed based on loop-mediated isothermal amplification (LAMP) combined with fluorescence resonance energy transfer (FRET) between GO and fluorescein isothiocyanate-labeled probe (FITC-probe). The fluorescence quenching efficiency of FITC-probe was found to increase with increasing GO concentration and reached 98.7% at a GO concentration of 50 MUg/ml. The fluorescence intensity of FITC-probe was recovered after hybridization with WSSV LAMP product with an optimal hybridization time of 10 min and increased accordingly with increasing amount of LAMP products. The detection limit was estimated to be as low as 10 copies of WSSV plasmid DNA or 0.6 fg of the total DNA extracted from shrimp infected with WSSV. In addition, no cross reaction was observed with other common shrimp viral pathogens. Therefore, the GO-FRET-LAMP technique is promising for fast, sensitive and specific detection of DNAs. PMID- 26277652 TI - Toking, Vaping, and Eating for Health or Fun: Marijuana Use Patterns in Adults, U.S., 2014. AB - INTRODUCTION: Policies legalizing marijuana for medical and recreational use have been increasing in the U.S. Considering the potential impact of these policies, important knowledge gaps exist, including information about the prevalence of various modes of marijuana use (e.g., smoked in joints, bowls, bongs; consumed in edibles or drinks) and about medical versus recreational use. Accordingly, this study assessed (1) prevalence and correlates of modes of current and ever marijuana use and (2) prevalence of medicinal and recreational marijuana use in U.S. adults. METHODS: Data came from Summer Styles (n=4,269), a nationally representative consumer panel survey of adults aged >=18 years, collected in 2014. The survey asked about past 30-day (current) and ever mode of marijuana use and current reason for use (medicinal, recreational, both). Weighted prevalence estimates were computed and correlates were assessed in 2014 using logistic regression. RESULTS: Overall, 7.2% of respondents reported current marijuana use; 34.5% reported ever use. Among current users, 10.5% reported medicinal-only use, 53.4% reported recreational-only use, and 36.1% reported both. Use of bowl or pipe (49.5%) and joint (49.2%) predominated among current marijuana users, with lesser use of bong, water pipe, or hookah (21.7%); blunts (20.3%); edibles/drinks (16.1%); and vaporizers (7.6%); 92.1% of the sample reported combusted-only marijuana use. CONCLUSION: Combusted modes of marijuana use are most prevalent among U.S. adults, with a majority using marijuana for recreation. In light of changing policies and patterns of use, improved marijuana surveillance is critical for public health planning. PMID- 26277654 TI - Influence of group II metals on Radium-226 concentration ratios in the native green plum (Buchanania obovata) from the Alligator Rivers Region, Northern Territory, Australia. AB - In this study, uptake of Ra from soil, and the influence of group II metals on Ra uptake, into the stones and edible flesh of the fruit of the wild green plum, Buchanania obovata, was investigated. Selective extraction of the exchangeable fraction of the soil samples was undertaken but was not shown to more reliably predict Ra uptake than total soil Ra activity concentration. Comparison of the group II metal to Ca ratios (i.e. Sr/Ca, Ba/Ca, Ra/Ca) in the flesh with exchangeable Ca shows that Ca outcompetes group II metals for root uptake and that the uptake pathway discriminated against group II metals relative to ionic radius, with uptake of Ca > Sr > Ba >> Ra. Flesh and stone analysis showed that movement of group II metals to these components of the plant, after root uptake, was strongly related. This supports the hypothesis that Sr, Ba and Ra are being taken up as analogue elements, and follow the same uptake and translocation pathways, with Ca. Comparison with previously reported data from a native passion fruit supports the use of total soil CRs on natural, undisturbed sites. As exchangeable CRs for Ra reach a saturation value it may be possible to make more precise predictions using selective extraction techniques for contaminated or disturbed sites. PMID- 26277653 TI - Fixation to features and neural processing of facial expressions in a gender discrimination task. AB - Early face encoding, as reflected by the N170 ERP component, is sensitive to fixation to the eyes. Whether this sensitivity varies with facial expressions of emotion and can also be seen on other ERP components such as P1 and EPN, was investigated. Using eye-tracking to manipulate fixation on facial features, we found the N170 to be the only eye-sensitive component and this was true for fearful, happy and neutral faces. A different effect of fixation to features was seen for the earlier P1 that likely reflected general sensitivity to face position. An early effect of emotion (~120 ms) for happy faces was seen at occipital sites and was sustained until ~350 ms post-stimulus. For fearful faces, an early effect was seen around 80 ms followed by a later effect appearing at ~150 ms until ~300 ms at lateral posterior sites. Results suggests that in this emotion-irrelevant gender discrimination task, processing of fearful and happy expressions occurred early and largely independently of the eye-sensitivity indexed by the N170. Processing of the two emotions involved different underlying brain networks active at different times. PMID- 26277655 TI - Safety and efficacy of an attenuated Chinese QX-like infectious bronchitis virus strain as a candidate vaccine. AB - Infectious bronchitis (IB) is a highly contagious respiratory and urogenital disease of chickens caused by infectious bronchitis virus (IBV). This disease is of considerable economic importance and is primarily controlled through biosecurity and immunization with live attenuated and inactivated IB vaccines of various serotypes. In the present study, we tested the safety and efficacy of an attenuated predominant Chinese QX-like IBV strain. The results revealed that the attenuated strain has a clear decrease in pathogenicity for specific-pathogen free (SPF) chickens compared with the parent strain. Strain YN-inoculated birds had clinical signs of varying severity with 30% mortality, while the attenuated group appeared healthy, with less tissue damage. The attenuated strain also had relatively low tissue replication rates and higher antibody levels. The superior protective efficacy of the attenuated strain was observed when vaccinated birds were challenged with a homologous or heterologous field IBV strain, indicating the potential of the attenuated YN (aYN) as a vaccine. Producing a vaccine targeting the abundant serotype in China is essential to reducing the economic impact of IB on the poultry industry. PMID- 26277656 TI - Pressurized intraperitoneal aerosol chemotherapy as an innovative approach to treat peritoneal carcinomatosis. AB - Peritoneal carcinomatosis (PC) is difficult to treat and many efforts have been made to identify effective and safe treatments. One hypothetical way to increase the efficacy of chemotherapy regarding tumor eradication or tumor control is to apply chemotherapeutic agents into the abdomen in the form of a pressurized aerosol, taking advantage of the physical properties of gas and pressure. This new approach for treatment of PC is based on the assumption that (1) intraabdominal application of chemotherapy under pressure will enhance tumor drug uptake and (2) aerosolizing and spraying chemotherapy will enhance the area of peritoneal surface covered by the drug, (3) resulting in an improved anti-tumor efficacy. Ex vivo and in vitro models have tested this approach and have demonstrated good peritoneal cavity coverage, deep peritoneal drug infiltration, and technical feasibility. Occupational safety of this procedure has also been established. First evidence in humans with peritoneal cancer from ovarian cancer, gastric cancer, colon cancer, appendiceal cancer, and pseudomyxoma peritonei has been obtained suggesting clinical antitumor activity and procedural safety of repeated pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin. We hypothesize that PIPAC can effectively treat PC and will hence become part of the surgical and chemotherapeutical treatment spectrum of this disease in the future. PMID- 26277657 TI - Type 5 and 6 nasal septal deformities: Could we predict and prevent acute coronary syndrome attacks in the future? AB - Undisturbed nasal breathing is essential for normal breathing physiology as a whole. Nasal septal deformities (NSD) are well known as a factor which can remarkably and substantially affect the quality of nasal and pulmonary breathing. However, it is well known that type 5 and type 6 nasal septal deformities may cause only a moderate, unilateral nasal obstruction or none at all. The effects of nasal obstruction on the respiratory and cardiovascular systems have been well studied so far: right ventricle problems, ischemic heart diseases, sleep disorders, mucociliary clearance system disturbances, paranasal sinus pathology, have all been described as a result of impaired nasal breathing. The connection between the upper and lower respiratory systems has been recognized in allergic rhinitis and asthma as well, resulting in the united airways concept. Most recently, the ostensible connection between chronic rhinosinusitis (CRS) and acute myocardial infarction has been said to be proven. However, the results of this study might have not been well founded since there are no direct and clear proofs that CRS as a chronic inflammatory process has anything to do with the acute coronary syndrome (ACS). On the other hand, a large international study on the incidence of NSD in CRS patients, based on the Mladina classification, showed that NSD were present in a high incidence and that the most frequent deformities were types 5 (36.18%) and 7 (29.92%). The vast majority of those types 7 consisted of types 3 and (again) types 5 or types 6 (76.32%). The fact that in CRS patients a remarkably high incidence of type 5 septal deformity can be seen, gives rise to thinking that this factor perhaps plays a role in the onset of ACS. Acute coronary syndrome is one of the leading causes of death all over the world. Traditional risk factors such as family history, overweight body, smoking, stress, hypertension, hypercholesterolemia, diabetes mellitus, coronary artery calcium score, C-reactive protein, lipoprotein, homocysteine, lipoprotein associated phospholipase A2, as well as high-density lipoprotein functionality perhaps cannot account for the entire risk for incident coronary events. Several other potential risk factors have been identified in an effort to improve risk assessment for ACS. This article reviews one of them: the possible influence of an unusual, so far unknown predisposing factor: type 5 or type 6 nasal septal deformities. They have been found as pure, isolated types or as a part of combined nasal septal deformity (type 7). PMID- 26277658 TI - Arterial tree asymmetry reduces cerebral pulsatility. AB - With each heartbeat, pressure wave (PW) propagates from aorta toward periphery. In cerebral circulation, at the level of circle of Willis (CW), four arteries and four PWs converge. Since the interference is an elemental property of the wave, PWs interfere at the level of CW. We hypothesize that the asymmetry of brain supplying arteries (that join to form CW) creates phase difference between the four PWs that interfere at the level of CW and reduce downstream cerebral pulsatility. To best of our knowledge, the data about the sequence of PWs' arrival into the cerebral circulation is lacking. Evident imperfect bilateral symmetry of the vessels results with different path length of brain-supplying arteries, hence, PWs should arrive into the head at different times. The probabilistic calculation shows that asynchronous arrival is more probable than synchronous. The importance of PWs for the cerebral circulation is highlighted by the observation that barotrauma protection mechanisms are more influenced by the crest of PW (pulse pressure) than by the mean arterial pressure. In addition, an increased arterial pulsatility is associated with several brain pathologies. We created simple computational models of four converging arteries and found that asynchronous arrival of the PWs results with lower maximum pressure, slower rate of pressure amplification and lower downstream pulsatility. In analogy, the asynchronous arrival of the pressure waves into the cerebral circulation should decrease blood flow pulsatility and lower transmission of kinetic energy on arterial wall. We conclude that asynchronous arrival of PWs into the cerebral circulation influences cerebral hemodynamics and represents a physiological necessity. PMID- 26277659 TI - Tumor targeting using polyamidoamine dendrimer-cisplatin nanoparticles functionalized with diglycolamic acid and herceptin. AB - Polymer mediated drug delivery system represents a novel promising platform for tumor-targeting with reduced systemic side effects and improved chemotherapeutical efficacy. In this study, we report the preparation and characterization of herceptin targeted, diglycolamic acid (DGA) functionalized polyamidoamine (PAMAM) dendrimer as a potent drug carrier for cisplatin. DGA dendrimers carrying cisplatin demonstrated enhanced anticancer activity when targeted with herceptin. In vitro cell line studies with herceptin-DGA-G4 cisplatin in HER-2 +ve and HER-2 -ve human ovarian cancer cell lines showed that these nanoparticles possessed remarkable features such as lower IC50 value, improved S-phase arrest, and enhanced apoptosis due to increased cellular uptake and accumulation than the untargeted DGA-G4-cisplatin and free cisplatin. Furthermore, in vivo results in SCID mice bearing SKOV-3 tumor xenografts, herceptin-DGA-G4-cisplatin, appeared to be more effective in inducing tumor regression as compared to free cisplatin. Collectively, these results indicate that herceptin targeted DGA functionalized PAMAM-cisplatin conjugates serve as better anti-tumor agents than individual therapeutic agents. PMID- 26277661 TI - Malaysian pathology spreading its canopy. PMID- 26277660 TI - A flexible-dose dispenser for immediate and extended release 3D printed tablets. AB - The advances in personalised medicine increased the demand for a fast, accurate and reliable production method of tablets that can be digitally controlled by healthcare staff. A flexible dose tablet system is presented in this study that proved to be suitable for immediate and extended release tablets with a realistic drug loading and an easy-to-swallow tablet design. The method bridges the affordable and digitally controlled Fused Deposition Modelling (FDM) 3D printing with a standard pharmaceutical manufacturing process, Hot Melt Extrusion (HME). The reported method was compatible with three methacrylic polymers (Eudragit RL, RS and E) as well as a cellulose-based one (hydroxypropyl cellulose, HPC SSL). The use of a HME based pharmaceutical filament preserved the linear relationship between the mass and printed volume and was utilized to digitally control the dose via an input from computer software with dose accuracy in the range of 91 95%. Higher resolution printing quality doubled the printing time, but showed a little effect on in vitro release pattern of theophylline and weight accuracy. Physical characterization studies indicated that the majority of the model drug (theophylline) in the 3D printed tablet exists in a crystal form. Owing to the small size, ease of use and the highly adjustable nature of FDM 3D printers, the method holds promise for future individualised treatment. PMID- 26277662 TI - IsomiRs have functional importance. AB - Since the inception of deep sequencing, isomiRs are consistently observed to be produced by most miRNA genes in a variety of cell types. IsomiRs appear as a variation in length from the canonical sequence annotated in miRBase, due to an addition or deletion of one or more nucleotides at the 5(') or 3(') ends or both. As the seed sequence is located at the 5(') end of the microRNA, the target mRNA will be theoretically different. Therefore, 5(')isomiRs might potentially target a new set mRNA compared to their canonical counterpart. This article gives an overview of investigations that explored the functional potential of isomiRs such as their ability to incorporate into Argonaute protein, the differential expression of isomiRs in various tissue types and cell lines, and the differences of mRNA targets between isomiR and its canonical microRNA. In addition, this article provides a brief introduction of RNA sponges as a potential way to inhibit isomiRs. PMID- 26277663 TI - Increased soluble HLA-DRB1in B-cell acute lymphoblastic leukaemia. AB - Soluble HLA (sHLA) are potential tumour markers released in order to counter immune surveillance. sHLA-class II is less known especially in acute lymphoblastic leukaemia (ALL). This study aimed to investigate soluble, surface and allelic expression of HLA Class II (sHLA-DR) in B-cell ALL patients and compare with soluble expression in normal individuals. A sandwich enzyme-linked immunosorbent assay (ELISA) was developed to measure soluble HLA-DRB1 in plasma. Flow cytometric analysis was performed to determine median fluorescence intensity in HLA-DR surface expression. HLA-DNA typing by polymerase chain reaction, sequence specific oligonucleotides, PCRSSO was performed to determine HLA-DRB1 type in ALL samples. Results showed sHLA-DRB1 (mean+/-SEM) was significantly increased (p=0.001) in plasma of ALL patients (0.260 +/-0.057 MUg/mL; n=30) compared to healthy controls (0.051 +/- 0.007ug/mL; n=31) of Malay ethnicity. However, these levels did not correlate with percentage or median fluorescence intensity of HLA-DR expressed on leukemia blasts (CD19+CD34 +/- CD45(lo)HLA-DR+) or in the normal B cell population (CD19+CD34- CD45(hi)HLA-DR+) of patients. No significant difference was observed in gender (male/female) or age (paediatric/adult). Only a trend in reduced sHLA was observed in patients carrying HLA-DR04. These results have to be validated with a larger number of samples. PMID- 26277664 TI - Gamma irradiation and red cell haemolysis: a study at the Universiti Kebangsaan Malaysia Medical Centre. AB - Gamma-irradiation of blood components is regarded a safe procedure used for prevention of transfusion associated graft-versus-host disease. However, reports showed that irradiation can cause erythrocyte haemolysis and damage to the RBC membrane. In University Kebangsaan Malaysia Medical Centre (UKMMC), a number of suspected transfusion reactions (TR) featured unusual isolated episodes of red coloured-urine or haemoglobinuria among paediatric patients without clinical features of acute haemolytic TR. Haemolysis of irradiated red cells was suspected as a cause. This study was conducted to evaluate haemolytic changes of RBC components following irradiation. A prospective, pre- and post- irradiation comparative study was conducted on 36 paired RBC-components in the blood-bank, UKMMC in the year 2013. Samples were tested for plasma-Hb, percent-haemolysis, plasma-potassium (K+) and lactate dehydrogenase (LDH) level. Post-irradiation mean plasma-Hb and percent-haemolysis were significantly higher than pre irradiation values at 0.09 +/-0.06g/dl VS 0.10 +/- 0.06g/dl and 0.19 +/- 0.13% VS 0.22 +/- .13% respectively, while plasma-K+ and LDH values did not show significant difference. However, the mean percent-haemolysis level was still within recommended acceptable levels for clinical use, supporting that irradiated RBC units were safe and of acceptable quality for transfusion. There was no conclusive reason for isolated haemoglobinuria following transfusion of irradiated red-cell products. Further research is suggested to investigate the other possible causes. PMID- 26277665 TI - Detection of chromosome 13 (13q14) deletion among Sudanese patients with multiple myeloma using a molecular genetics fluorescent in situ hybridization technique (FISH). AB - Multiple myeloma (MM) is a neoplastic plasma cell dyscrasia with an incidence of 4-4.5 per 100,000 population per year. It is regarded as the second most prevalent blood cancer (10%) after non-Hodgkin lymphoma. The objective of this study was to investigate the mutational change in chromosome 13 (13q14) among Sudanese MM patients and to identify the association between extent of plasma cell infiltration in the bone marrow, albumin level and deletion of 13q14 by an analytical case control study. MATERIALS AND METHODS: 15 patients were enrolled in the study. 11 bone marrow samples were collected from MM patients at different stages of the disease and 4 samples were from patients with conditions other than MM as control. Plasma cells were counted from bone marrow smears and fluorescence in-situ hybridization (FISH) was performed using Fluorophore labeled DLEU1 (13q14) LSI (local specific identifier) probe designed as a dual-colour assay to detect deletion at 13q14. Heparanized sample was taken for estimation of serum albumin in all patients. RESULTS: 13q14 deletion was detected in 6 (54.5%) MM patients while one (9.1%) patient showed monosomy. All relapsed MM (27.3%) had 13q14 deletion. Surprisingly almost all patients studied had normal albumin level. The study could not show whether the deletion is implicated in the pathogenesis of multiple myeloma. PMID- 26277666 TI - Diagnostic flex-rigid pleuroscopic biopsy of parietal pleura for exudative pleural effusions in suspected malignant and tuberculosis cases: a retrospective study of 219 cases. AB - OBJECTIVES: This study was carried out to ascertain the aetiology of exudative pleural effusions when other diagnostic investigations such as pleural fluid and sputum examination for cytology and acid fast bacilli fail to yield a definitive diagnosis and to differentiate between tuberculosis and malignancy in cases suspicious of malignancy. METHODS: Pleuroscopic biopsies were obtained in 219 cases by Chest Physicians in the endoscopy suite using flexi-rigid fiber-optic pleuroscopes. Histological sections were stained with H&E and microscopic examination performed. Ziehl-Nielsen stain for acid fast bacilli was performed in all suspected tuberculosis cases and immunohistochemistry for Thyroid transcription factor 1 and other markers were carried out for all cases suspicious of malignancy. RESULTS: Adequate biopsy material for interpretation was obtained in 210 (95.9%) of 219 cases. Histopathology revealed 79 (37.6%) cases were tuberculosis, 64 (30.5%) were malignant (primary from lung and other sites), 62 (29.5%) were non-specific inflammation and 5 (2.4%) were empyema. A definitive diagnosis of tuberculosis, malignancy and empyema was obtained in 70.5% of cases. Tuberculosis was encountered in a younger age-group than malignancy. Mean age for tuberculosis patient was 49 years while for malignant patients was 63 years. The majority (79.6%) of malignances encountered were metastatic lung adenocarcinoma. PMID- 26277667 TI - Comparison of Abtectcell III and Diamed red cell antibody screening kit for detection of clinically significant red cells alloantibody. AB - Antibody screening is important for the antenatal screening and pre-transfusion tests. This study aimed to compare the MUT/Mur kodecytesAbtectcell III (CSL Abtectcell III) red cell antibody screening kit with DiaMed ID-Dia Cell I-II-III Asia that was then used in our laboratory. In this study, 125 samples were randomly chosen, with 67 samples of known antibody specificities and 58 samples identified as negative for antibody, as the negative control. Concordant negative results were obtained in 57 out of 58 antibody negative samples. Concordant antibody positive results with both reagents were seen in 49 out of 67 samples. There were 18 discrepant results of antibody screening with CSL Abtetcell III (16/18 for vMNS antibodies). The sensitivity and specificity for CSL Abtectcell III were 73.0% and 98.3% respectively. In conclusion, the CSL Abtectcell III reagent would be an acceptable alternative for screening of red cell alloantibodies. It was able to detect all the clinically significant alloantibodies. PMID- 26277668 TI - Tumour morphology after neoadjuvant chemotherapy as a predictor of survival in serous ovarian cancer: an experience from a tertiary care centre in India. AB - Serous ovarian cancer is the most common malignant ovarian tumour. Traditional management consists of surgical resection with postoperative chemotherapy. Currently neoadjuvant chemotherapy is offered to patients with advanced stage disease. The present study aims to analyse the histomorphological alterations in serous ovarian cancer following neoadjuvant chemotherapy. Correlation of these morphological alterations with survival is also presented here. Serous ovarian cancers from 100 advanced stage cases were included; 50 were treated with pre surgery chemotherapy. Semi-quantitative scoring was used to grade the alterations in tumour morphology. Survival data was correlated with the final morphological score. Tumour morphology was significantly different in cases treated with neoadjuvant chemotherapy (CT group) as compared to cases with upfront surgery. The CT group cases showed more fibrosis, calcification, and infiltration by lymphocytes, plasma cells, foamy and hemosiderin-laden macrophages. The residual tumour cells had degenerative cytoplasmic changes with nuclear atypia. Patients with significant morphological response had a longer median survival, although it did not attain statistical significance in the current study. With the increasing use of neoadjuvant chemotherapy in management, the pathologist needs to be aware of the altered morphological appearance of tumour. Further studies are required to establish a grading system to assess the tissue response which can be helpful in predicting the overall therapeutic outcome and the prognosis of patients. PMID- 26277669 TI - Effectiveness of bone cleaning process using chemical and entomology approaches: time and cost. AB - Skeletal examination is an important aspect of forensic pathology practice, requiring effective bone cleaning with minimal artefact. This study was conducted to compare between chemical and entomology methods of bone cleaning. Ten subjects between 20 and 40 years old who underwent uncomplicated medico-legal autopsies at the Institute of Forensic Medicine Malaysia were randomly chosen for this descriptive cross sectional study. The sternum bone was divided into 4 parts, each part subjected to a different cleaning method, being two chemical approaches i.e. laundry detergent and a combination of 6% hydrogen peroxide and powder sodium bicarbonate and two entomology approaches using 2nd instar maggots of Chrysomyia rufifacies and Ophyra spinigera. A scoring system for grading the outcome of cleaning was used. The effectiveness of the methods was evaluated based on average weight reduction per day and median number of days to achieve the average score of less than 1.5 within 12 days of the bone cleaning process. Using maggots was the most time-effective and costeffective method, achieving an average weight reduction of 1.4 gm per day, a median of 11.3 days to achieve the desired score and an average cost of MYR 4.10 per case to reach the desired score within 12 days. This conclusion was supported by blind validation by forensic specialists achieving a 77.8% preference for maggots. Emission scanning electron microscopy evaluation also revealed that maggots especially Chrysomyia rufifacies preserved the original condition of the bones better allowing improved elucidation of bone injuries in future real cases. PMID- 26277670 TI - Routine diabetes screening in blood donation campaigns. AB - BACKGROUND: Data from the National Health and Morbidity Survey 2011 showed that 20.8% of Malaysians above 30 years have diabetes. 10.1%of them are undiagnosed. Mobile blood drives could complement the public health department efforts in diabetes screening for early detection of the illness. AIMS: This study aims to determine the necessity of diabetes screening as a routine screening program during blood donation campaign. METHODS AND MATERIAL: Blood donation campaigns which involved the public community between January 2013 and June 2013 were included in this study. Donors above 30-years-old, not known to have diabetes, consented for diabetes screening. Diabetes screening was done by checking random capillary blood sugar (RCBS) levels while performing a Hemoglobin test and ABO grouping. Donors with RCBS of >= 7.8 mmol/L were given appointments for oral glucose tolerance test (OGTT) to confirm the diagnosis of diabetes. RESULTS: A total of 211 diabetes screenings were performed. Mean RCBS was 6 mmol/L. 43(20.4%) donors had RCBS>= 7.8 mmol/L. 10 donors were later diagnosed to have diabetes (5.0%) and 5 donors were prediabetes (2.5%). 9 donors (4.3%) did not turn up for further investigation. CONCLUSIONS: Blood donors are expected to be healthy volunteers. The diabetes prevalence among blood donors (5.0%) is considered low if compared with the prevalence in the whole population (20.8%). However, the number is largely comparable to the prevalence of undiagnosed diabetes in the country (10.1%). Routine diabetes screening during blood donation campaign should be implemented to safeguard donors' health and serve as a public health initiative to improve community health. PMID- 26277671 TI - Pseudotumour cerebri in acute promyelocytic leukemia on treatment with all-trans retinoic acid (ATRA) - an experience from a tertiary care centre. AB - Acute promyelocytic leukemia (APML) is considered to be sensitive to all-trans retinoic acid (ATRA) which acts as a differentiating agent. ATRA is considered to be a well-tolerated agent and is known to achieve complete remission in acute promyelocytic leukemia. However, a few cases on long term all-trans-retinoic acid (ATRA) use can develop pseudotumor cerebri. Out of 32 patients with APML who were treated in our Centre over a 4-year-period, we encountered 6 patients who developed ATRA-related pseudotumor cerebri while on maintenance treatment. The patients ranged from 12 to 40 years of age. 3 patients complained of unbearable headache, 2 of diplopia and 1 of gross reduction in visual acuity. CT scans and MRI did not reveal any intracranial lesions. Cerebrospinal fluid (CSF) examination was normal with CSF manometry revealing a high CSF pressure (average of 345mmH2O). Fundoscopy revealed papilledema in 5 patients and optic atrophy in 1 patient. The patients were successfully managed with decrease dose/discontinuation of ATRA, use of acetazolamide, corticosteroids and therapeutic CSF drainage. PMID- 26277672 TI - A rare case of combined placental site trophoblastic tumour with mature cystic teratoma and mixed germ cell tumour in the testis. AB - A 20-year-old male presented with persistent right testicular pain. Following ultrasound detection of testicular nodules and biopsy for intraoperative consultation which yielded germ cell tumour, he underwent radical orchidectomy. A predominantly whitish cyst and a lobulated, variegated nodule were identified. Histology showed a mature cystic teratoma with a focus of infiltrative epithelioid cells containing eosinophilic cytoplasm and pleomorphic nuclei, invading ectatic vessel wall associated with fibrinoid change. These cells were positive for cytokeratin, human placental lactogen and inhibin, while negative for Melan-A, p63 and alpha-fetoprotein, consistent with placental site trophoblastic tumor (PSTT). The variegated nodule was a mixed germ cell tumour composed of embryonal carcinoma and immature teratoma. Aside from choriocarcinoma, primary trophoblastic tumors such as PSTT, which are derived from intermediate trophoblasts, are extremely rare in the testis. Aside from a case of pure testicular PSTT, 2 other cases have been described in association with germ cell tumour, of which one is a mature teratoma with PSTT that demonstrated gain of chromosome 12p. The other presented with PSTT in retroperitoneal recurrence of a testicular mixed germ cell tumour. We discussed the features of this tumour in the testis and important differentials in its diagnosis. PMID- 26277673 TI - Obstructive jaundice in small cell lung carcinoma. AB - Small cell lung carcinoma (SCLC) commonly metastasizes to distant organs. However, metastasis to the pancreas is not a common event. Moreover, obstructive jaundice as a first clinical presentation of SCLC is extremely unusual. This case reports a 51-year-old male with SCLC, manifesting with obstructive jaundice as the initial clinical presentation. Endoscopic retrograde cholangiopancreatograghy (ERCP) and abdominal computed tomography (CT) scan showed a mass at the head of the pancreas. The patient underwent pancreatoduodenectomy (Whipple procedure). Histopathology revealed a chromogranin- A-positive poorly-differentiated neuroendocrine carcinoma of the pancreas. No imaging study of the lung was performed before surgery. A few months later, a follow-up CT revealed unilateral lung nodules with ipsilateral hilar nodes. A lung biopsy was done and histopathology reported a TTF- 1-positive, chromogranin A-positive, small cell carcinoma of the lung. On review, the pancreatic tumour was also TTF-1-positive. He was then treated with combination chemotherapy (cisplatin, etoposide). These findings highlight that presentation of a mass at the head of pancreas could be a manifestation of a metastatic tumour from elsewhere such as the lung, and thorough investigations should be performed before metastases can be ruled out. PMID- 26277674 TI - Molecular characterization of two Malaysian patients with Wiskott-Aldrich syndrome. AB - The Wiskott-Aldrich Syndrome (WAS) is an X-linked immunodeficiency condition characterized by microthrombocytopenia, eczema and recurrent infections. It is caused by mutations in the Wiskott-Aldrich Syndrome protein (WASP) gene. We investigated two Malay boys who presented with congenital thrombocytopenia, eczema and recurrent infections. Here we report two cases of WASP mutation in Malaysia from two unrelated families. One had a novel missense mutation in exon 1 while the other had a nonsense mutation in exon 2. Both patients succumbed to diseaserelated complications. A differential diagnosis of WAS should be considered in any male child who present with early onset thrombocytopenia, especially when this is associated with eczema and recurrent infections. PMID- 26277675 TI - Triple cancer: chronic lymphocytic leukemia with bladder and prostate carcinoma. AB - B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a common lymphoproliferative disorder with an increased risk of developing subsequent neoplasms of epithelial and mesenchymal origin. The decreased immunity and B-cell dysfunction in CLL probably accounts for this emergence of second malignancies. We report a case of synchronous bladder transitional cell carcinoma (TCC) and prostatic carcinoma with CLL. A 74-year-old male who underwent transurethral resection of the prostate (TURP) for benign prostatic hyperplasia 2 years before, presented with recurrent urinary tract infection. Peripheral blood smear revealed leukocytosis with absolute lymphocytosis (absolute lymphocyte count: 37870 cells/mm3). Flow cytometric immunophenotyping revealed 75% abnormal lymphoid cells which were positive for CD 19, CD5, CD23, CD22, CD200, CD20 (moderate) with lambda light chain restriction and negative for CD3, CD10, FMC7, CD38, CD138, IgM, CD103, CD123. F Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) showed increased metabolic activity of the left lateral wall of the urinary bladder extending to the left UV junction, adjacent part of trigone and bladder neck region along with multiple heterogeneous enhancing areas with increased FDG avidity within the prostate. Transurethral resection of the bladder tumour by cystoscopy was performed. Histopathology showed high grade, muscle invasive urothelial carcinoma. Due to presence of uptake in the prostate, transurethral resection of the prostate was done and histopathology revealed adenocarcinoma of prostate (prostate specific antigen- positive), Gleason grade III+III and Gleason score 6. A high index of suspicion is required to detect synchronous and metachronous malignancies. Ancillary studies such as immunohistochemistry, flow cytometry and PET/CT are often essential for detection and an accurate diagnosis. PMID- 26277676 TI - Guidelines for nucleic acid detection and analysis in hematological disorders. PMID- 26277677 TI - Previous Pregnancies Among Young Women Having an Abortion in England and Wales. AB - PURPOSE: The purpose of this study was to use national statistics on abortions carried out in England and Wales to more precisely estimate the proportion of young women aged <20 years obtaining an abortion who have had one or more previous pregnancies. METHODS: Secondary analysis of abortion data from the Office of National Statistic and the Department of Health by parity for women aged <20 years, ordinarily residing in England and Wales, from 1992 to 2013. RESULTS: Over the past 20 years, the proportion of teenagers in England and Wales having an abortion as a result of a subsequent pregnancy increased by 33% (from .172 in 1992 to .229 in 2013). Most of this increase occurred before 2004, and the proportion now appears to have stabilized. In 2013, 22.9% of the young women aged <20 years who underwent an abortion had had at least one previous pregnancy (either a birth or an abortion). Only a minority (<5% of young women who obtained an abortion) had had more than one previous pregnancy. CONCLUSIONS: The findings show that nearly one in four teenagers presenting for an abortion have already been in contact with health services for a previous birth or abortion. Greater policy emphasis must be placed on the accurate identification of the proportion of teenage pregnancies that occur as a result of a subsequent pregnancy and developing more effective "secondary prevention" interventions to help the first time pregnant and parenting teenagers manage their future reproductive lives and prevent further unplanned pregnancies. PMID- 26277678 TI - Sexual and Reproductive Health Among Ugandan Youth: 2003-04 to 2012. AB - PURPOSE: Suboptimal sexual and reproductive health (SRH) increases morbidity, mortality, and gender inequity and slows development. In Uganda, youths represent 20% of the population, and the burden of sexually transmitted infections (STIs), including human immunodeficiency virus (HIV), is substantial. METHODS: We analyzed survey data collected using the lot quality assurance sampling (LQAS) technique from two time periods, 2003-2004 and 2012. We assessed knowledge, behaviors, and access to SRH services of youths aged 15-24 years. Using logistic regression, we examined factors associated with these indicators. RESULTS: All indicators have improved between the early and later time period. Youths knowing where to get HIV tests increased from <40% to 80% (both sexes); the number of youths reporting ever having an HIV test increased from 8% to 48% (males) and 10% to 64% (females). Knowledge of other STIs improved but remains low; only half of respondents know signs and symptoms of STIs, and less than half know what action to take when infected. In the late period, 85% of female youths, compared with 93% of males reported knowing where to obtain condoms. The proportion of youths reporting sexual debut before age 15 years decreased, less so for males than that for females. Increased age and level of education are associated with positive change for most indicators. CONCLUSIONS: Over the last decade, progress has been made toward improving the SRH of young people in Uganda. Further efforts are required to ensure universal access and sufficient health education to facilitate the continued improvement of safe sexual behaviors among youth aged 15-24 years. PMID- 26277679 TI - Neuroanatomical correlates of late-life depression and associated cognitive changes. AB - We compared cortical thickness between patients with late-life depression (LLD) and healthy controls and between patients with early-onset (EOD) and late-onset (LOD) depression. We also tested age effects on cortical thickness in LLD and controls and if cortical thickness and hippocampal volumes were associated with cognitive performance in LLD. Three-dimensional T1-weighted magnetic resonance images were obtained in 49 LLD and 49 matched hospital controls and processed using FreeSurfer. General linear model analysis was used as a statistical approach. LLD group had thinning in the left parahippocampal, fusiform, and inferior-parietal cortex compared with controls. Age correlated with cortical thinning in controls but not in LLD. Women in the LOD groups had extensive cortical thinning in the lateral prefrontal cortex bilaterally compared with EOD women. Absence of statistically significant changes observed in men should however be treated with caution because of the low number of men in the study. Mini-Mental Status Examination score correlated with lateral prefrontal cortical thickness bilaterally and hippocampal volume in the total group of LLD and in LOD but not EOD. LLD is associated with cortical thinning, which is associated with age at depression onset, gender, and level of cognitive functioning. PMID- 26277680 TI - Delivery of a Vitamin D Intervention in Homebound Older Adults Using a Meals-on Wheels Program: A Pilot Study. AB - OBJECTIVES: To assess the feasibility of a vitamin D intervention delivered through a Meals-on-Wheels (MOW) program to improve 25-hydroxyvitamin D (25(OH)D) concentrations and reduce falls in homebound older adults. DESIGN: Single-blind, cluster randomized trial. SETTING: MOW, Forsyth County, North Carolina. PARTICIPANTS: Community-dwelling homebound adults aged 65 to 102 (N = 68). INTERVENTION: MOW clients were randomized to vitamin D3 (100,000 IU/month; n = 38) or active placebo (400 IU vitamin E/month; n = 30) according to MOW delivery route. MEASUREMENTS: Serum 25(OH)D was assessed at baseline and 5-month follow up; proportions of participants in 25(OH)D categories were compared using Fisher exact test. Falls were assessed using monthly fall calendars, and rate of falls was estimated using negative binomial generalized estimating equation models. RESULTS: Mean +/- standard deviation 25(OH)D concentrations were 20.9 +/- 11.5 ng/mL at baseline, with 57% having 25(OH)D concentrations less than 20 ng/mL. Retention and adherence were high (>90%). After the 5-month intervention, only one of 34 participants randomized to vitamin D3 had 25(OH)D concentrations less than 20 ng/mL, compared with 18 of 25 participants randomized to placebo (P < .001). In unadjusted analyses, the rate of falls over 5 months was not significantly different according to intervention group (risk ratio (RR) = 0.48, 95% confidence interval (CI) = 0.19-1.19), but after adjustment for sex, race, season of year, baseline 25(OH)D status, and history of falls, participants randomized to vitamin D3 had a lower rate of falling than those randomized to placebo (RR = 0.42, 95% CI = 0.21-0.87). CONCLUSION: A vitamin D intervention delivered through MOW was feasible, resulting in improvements in 25(OH)D concentrations and a lower rate of falls in adjusted analyses. Further research is needed to validate the reduction in falls from this type of intervention. PMID- 26277681 TI - Fibronectin unfolded by adherent but not suspended platelets: An in vitro explanation for its dual role in haemostasis. AB - Fibronectin (FN), a dimeric adhesive glycoprotein, which is present both in plasma and the extracellular matrix can interact with platelets and thus contribute to platelet adhesion and aggregation. It has been shown that FN can decrease platelet aggregation but enhance platelet adhesion, suggesting a dual role of FN in haemostasis. The prevalent function(s) of FN may be determined by its fibril form. To explore the suggested dual role of this adhesive protein for haemostasis in further detail, we now tested for any differences of adherent and suspended platelets with regard to their effect to unfold and assemble FN upon interaction. Platelet aggregation and adhesion assays were performed using washed platelets in the presence of exogenous FN. Addition of plasma FN reduced platelet aggregation in response to collagen or PMA by 50% or 25% but enhanced platelet adhesion onto immobilized collagen, as compared to control experiments. Analyses by fluorescence resonance energy transfer (FRET) demonstrated that adherent platelets but not suspended platelets were capable of unfolding FN during 3h incubation. Fluorescence microscopy and deoxycholate (DOC) solubility assays demonstrated that FN fibrils formed only on the surfaces of adherent platelets. In addition, platelets adherent onto FN revealed a significantly higher activity of specific Src phosphorylation (pY418) than platelets in suspension. These data suggest (1) that the function of FN in haemostasis is prevalent to its assembly, unfolding and subsequent fibril formation on the surface of adherent platelets and (2) that outside-in signaling contributes to the interaction of platelets and FN. PMID- 26277682 TI - Safety and efficacy of direct oral anticoagulants compared to warfarin for extended treatment of venous thromboembolism -a systematic review and meta analysis. AB - OBJECTIVE: To examine and compare the safety and efficacy of extended treatment with dabigatran, apixaban, rivaroxaban and warfarin in patients with unprovoked venous thromboembolism. METHODS: PubMed and Embase were searched for randomized clinical trials reporting on the use of direct oral anticoagulants (DOACs) and warfarin for the extended treatment of VTE. Meta-analysis was performed on studies reporting similar study design and comparator. RESULTS: A total of 729 articles were identified and 5 studies covering 6 randomized clinical trials met the eligibility criteria and were included in the study. 5 studies were included in the meta-analysis. Results from the meta-analysis showed that the extended use of DOACs and warfarin significantly decreased the risk of recurrent VTE with 83 % when compared placebo. Warfarin (RR: 0.03, CI: 0.00-0.49) and dabigatran (RR: 0.08, CI: 0.03-0.27) showed the largest relative risk reduction followed by apixaban 2.5mg (RR: 0.19, CI: 0.11-0.33), rivaroxaban (RR:0.19, CI: 0.09-0.40) and apixaban 5mg (RR: 0.20, CI: 0.11-0.34). No significant increased risk of major bleeding was observed with the extended use of any DOACs and warfarin compared to placebo (1.15, CI: 0.40-3.31), but an overall increased risk of non major clinically relevant bleeding (NMCRB) was observed (RR: 2.12, CI: 1.55 2.90). Apixaban 2.5mg and warfarin was not individually associated with an increased risk of NMCRB. Furthermore, it was found from a study not included in the meta-analysis that dabigatran was non-inferior to VKA for the prevention of recurrent VTE (HR: 1.44, CI: 0.78-2.64, p=0.01 for noninferiority) and decreased the risk of NMCRB compared to VKA (RR: 0.58, CI: 0.43-0.77). CONCLUSION: Extended treatment with both warfarin and DOACs are effective in preventing recurrent VTE and does not increase the risk of major bleeding, but increases the risk of NMCRB. PMID- 26277683 TI - Return to work after general surgery: A comparative study. AB - PURPOSES: There is scarce information on the time to return to work after general surgery. The aim of this study was to analyze time off work after elective cholecystectomy and to compare the results with those in patients undergoing other surgical interventions. METHODS: Observational and comparative study. Inclusion criteria were: being of working age and undergoing elective laparoscopic cholecystectomy (group 1) or unilateral inguinal hernia or haemorrhoidectomy (group 2). RESULTS: 36 patients were included: 18 patients in each group. Overall, return to work occurred at a mean of 35.7 days, with no significant differences (p=0.656) between groups (group 1: 36.6 days vs. group 2: 35.44 days). The reasons for not returning to work earlier were fear of complications (37.5%), pain control (37.5%), surgeon recommendation (12.5%), and general practitioner recommendation (12.5%). CONCLUSIONS: Time to recovery after laparoscopic cholecystectomy is prolonged. No statistically significant differences with less complex surgical procedures were detected. PMID- 26277685 TI - "GAG-ing with the neuron": The role of glycosaminoglycan patterning in the central nervous system. AB - Proteoglycans (PGs) are a diverse family of proteins that consist of one or more glycosaminoglycan (GAG) chains, covalently linked to a core protein. PGs are major components of the extracellular matrix (ECM) and play critical roles in development, normal function and damage-response of the central nervous system (CNS). GAGs are classified based on their disaccharide subunits, into the following major groups: chondroitin sulfate (CS), heparan sulfate (HS), heparin (HEP), dermatan sulfate (DS), keratan sulfate (KS) and hyaluronic acid (HA). All except HA are modified by sulfation, giving GAG chains specific charged structures and binding properties. While significant neuroscience research has focused on the role of one PG family member, chondroitin sulfate proteoglycan (CSPG), there is ample evidence in support of a role for the other PGs in regulating CNS function in normal and pathological conditions. This review discusses the role of all the identified PG family members (CS, HS, HEP, DS, KS and HA) in normal CNS function and in the context of pathology. Understanding the pleiotropic roles of these molecules in the CNS may open the door to novel therapeutic strategies for a number of neurological conditions. PMID- 26277684 TI - Development and functional characterization of extrahepatic cholangiocyte lines from normal rats. AB - BACKGROUND: Since limited in vitro tools exist for evaluating the pathophysiology of extrahepatic bile ducts, we aim to develop an extrahepatic cholangiocyte culture system from normal rats. METHODS: Extrahepatic ducts were dissected from rats, cut in half length-wise and cultured on collagen-I coated plates. Transepithelial electrical resistance was measured. At ~85% confluence, in extrahepatic cholangiocytes we measured: (i) cell size and distribution, and expression for cytokeratin-19, secretin, secretin receptor and somatostatin receptor type II (SSTR2), cystic fibrosis transmembrane conductance regulator (CFTR), chloride bicarbonate anion exchanger 2 (AE2), vascular endothelial growth factor-A (VEGF-A) and nerve growth factor (NGF); and (ii) the effect of secretin and/or somatostatin on 3'-5'-cyclic adenosine monophosphate (cAMP) levels and proliferation. RESULTS: Cytokeratin-positive extrahepatic cholangiocytes were cultured for 6 passages to form a cell monolayer. Cholangiocytes proliferated to confluence over a 2-week period. The size of extrahepatic cholangiocytes averaged ~16 MUm. Extrahepatic ducts and cholangiocytes were positive for secretin, secretin receptor and SSTR2, CFTR, AE2, VEGF-A and NGF. In extrahepatic cholangiocyte cultures, secretin increased cAMP (prevented by somatostatin), chloride efflux and proliferation. CONCLUSIONS: Extrahepatic cholangiocyte cultures may be important for studying diseases targeting extrahepatic cholangiocytes such as biliary atresia. PMID- 26277687 TI - Requirement of keratan sulfate proteoglycan phosphacan with a specific sulfation pattern for critical period plasticity in the visual cortex. AB - Proteoglycans play important roles in regulating the development and functions of the brain. They consist of a core protein and glycosaminoglycans, which are long sugar chains of repeating disaccharide units with sulfation. A recent study demonstrated that the sulfation pattern of chondroitin sulfate on proteoglycans contributes to regulation of the critical period of experience-dependent plasticity in the mouse visual cortex. In the present study, we investigated the role of keratan sulfate (KS), another glycosaminoglycan, in critical period plasticity in the mouse visual cortex. Immunohistochemical analyses demonstrated the presence of KS containing disaccharide units of N-acetylglucosamine (GlcNAc) 6-sulfate and nonsulfated galactose during the critical period, although KS containing disaccharide units of GlcNAc-6-sulfate and galactose-6-sulfate was already known to disappear before that period. The KS chains were distributed diffusely in the extracellular space and densely around the soma of a large population of excitatory and inhibitory neurons. Electron microscopic analysis revealed that the KS was localized within the perisynaptic spaces and dendrites but not in presynaptic sites. KS was mainly located on phosphacan. In mice deficient in GlcNAc-6-O-sulfotransferase 1, which is one of the enzymes necessary for the synthesis of KS chains, the expression of KS was one half that in wild type mice. In the knockout mice, monocular deprivation during the critical period resulted in a depression of deprived-eye responses but failed to produce potentiation of nondeprived-eye responses. In addition, T-type Ca(2+) channel dependent long-term potentiation (LTP), which occurs only during the critical period, was not observed. These results suggest that regulation by KS-phosphacan with a specific sulfation pattern is necessary for the generation of LTP and hence the potentiation of nondeprived-eye responses after monocular deprivation. PMID- 26277686 TI - Combination therapy with lenalidomide and nanoceria ameliorates CNS autoimmunity. AB - OBJECTIVE: Multiple sclerosis (MS) is a debilitating neurological disorder involving an autoimmune reaction to oligodendrocytes and degeneration of the axons they ensheath in the CNS. Because the damage to oligodendrocytes and axons involves local inflammation and associated oxidative stress, we tested the therapeutic efficacy of combined treatment with a potent anti-inflammatory thalidomide analog (lenalidomide) and novel synthetic anti-oxidant cerium oxide nanoparticles (nanoceria) in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. METHODS: C57BL/6 mice were randomly assigned to a control (no EAE) group, or one of the four myelin oligodendrocyte glycoprotein-induced EAE groups: vehicle, lenalidomide, nanoceria, or lenalidomide plus nanoceria. During a 23 day period, clinical EAE symptoms were evaluated daily, and MRI brain scans were performed at 11-13 days and 20-22 days. Histological and biochemical analyses of brain tissue samples were performed to quantify myelin loss and local inflammation. RESULTS: Lenalidomide treatment alone delayed symptom onset, while nanoceria treatment had no effect on symptom onset or severity, but did promote recovery; lenalidomide and nanoceria each significantly attenuated white matter pathology and associated inflammation. Combined treatment with lenalidomide and nanoceria resulted in a near elimination of EAE symptoms, and reduced white matter pathology and inflammatory cell responses to a much greater extent than either treatment alone. INTERPRETATION: By suppressing inflammation and oxidative stress, combined treatment with lenalidomide and nanoceria can reduce demyelination and associated neurological symptoms in EAE mice. Our preclinical data suggest a potential application of this combination therapy in MS. PMID- 26277688 TI - Aging-associated subpopulations of human CD8+ T-lymphocytes identified by their CD28 and CD57 phenotypes. AB - BACKGROUND: During organismal aging, human T-cells shift towards less functional phenotypes, often called senescent cells. As these cells have not been well characterized, we aimed to relate surface markers of human T-cell senescence with characteristics of in vitro cellular aging and to further characterize these cells. METHODS: We identified, by flow cytometry, subpopulations of CD8+ T-cells based on CD57 and CD28 expression, and tested them for some markers of cellular senescence, apoptosis, differentiation and homing. RESULTS: Elderly persons presented significantly higher proportions not only of CD28-CD57+, but also of CD28+CD57+ cells. CD28+CD57+ cells had the highest expression of p16, p21, Bcl-2, CD95, CD45RO, CCR5 and PD-1, thereby arguing in favor of a senescent phenotype. CONCLUSION: Among CD8+ T-lymphocytes, CD28+CD57+ cells represent a subset with some senescent features that are distinct from the CD28-CD57+ cells. PMID- 26277689 TI - The effect of offspring on depressive disorder among old adults: Evidence from the Korean Longitudinal Study of Aging from 2006 to 2012. AB - OBJECTIVE: To investigate whether having an offspring protects against or increases the risk of depressive disorders. METHODS: Data from the Korean Longitudinal Study of Aging (KLoSA) from 2006 and 2012 was assessed using longitudinal data analysis. We have included 10,149 research subjects at baseline and estimated the prevalence of depressive disorders for those with children. RESULTS: The number of offspring was from zero to five or more, and the composition of offspring is from zero boys and zero girls to two or more boys and two or more girls. For parents with zero offspring, the estimate for depressive disorder was 0.464 higher (SE: 0.123, p-value: 0.000, OR: 1.389; 95% CI: 1.176 1.640) and for parents with five or more offspring, the estimate for depressive disorder was 0.1 higher (SE: 0.104, p-value: 0.013, OR: 1.315; 95% CI: 1.150 1.504) compared to parents with two offspring. For parents with zero boys and zero girls, the estimate for depressive disorder was 0.599 higher (SE: 4.750, p value: <0.0001, OR: 1.539; 95% CI: 1.298-1.825), and for parents with two or more boys and two or more girls, the estimate for depressive disorder was 1.328 higher (SE: 3.820, p-value: 0.000, OR: 1.328; 95% CI: 1.189-1.482) compared to parents with one boy and one girl. CONCLUSIONS: Our results indicate that there is a large effect of offspring on the prevalence of depressive disorder, with significant positive effects for mothers. Fathers are at lower risk for depressive disorder than mothers, and the graph was U-shaped. PMID- 26277690 TI - Intersphincteric completion proctectomy with omentoplasty for chronic presacral sinus after low anterior resection for rectal cancer. AB - AIM: This study aimed to determine the clinical outcome of salvage surgery without restoring continuity for symptomatic chronic presacral sinus after low anterior resection (LAR) for rectal cancer. METHOD: Out of a prospective cohort of 46 patients with chronic presacral sinus (> 1 year after LAR), 27 underwent completion proctectomy with omentoplasty between January 2005 and July 2014. RESULTS: The initial treatment for rectal cancer included neoadjuvant radiotherapy in 26 (96%) patients. Besides a chronic presacral sinus, a secondary fistula was present in 15 (56%) patients. Definitive salvage surgery was performed after a median of 40 (12-350) months from the primary resection. The median hospital stay after single- and multiple-stage salvage surgery was 11 and 17 days. Postoperative complications occurred in 44% of patients. The re intervention rate was 33% with a range of 1-10 interventions per patient. During a median follow-up of 20 (4-45) months from salvage surgery, healing of the chronic presacral sinus occurred in 78% of patients, with a healing rate after single- and multiple-stage procedures of 88% and 64% respectively (P = 0.19). CONCLUSION: Patients with a symptomatic chronic presacral sinus after LAR for rectal cancer, in whom restoration of continuity is not intended, can be effectively managed by completion proctectomy with complete debridement of the sinus and fistula tracts followed by an omentoplasty to fill the presacral cavity, preferably as a single-stage procedure. PMID- 26277691 TI - Turning the page. PMID- 26277693 TI - Corrigendum. PMID- 26277697 TI - Dexamethasone-suppressed corticotropin-releasing hormone stimulation test in morbid obese adults. AB - PURPOSE: In order to differentiate between Cushing's syndrome (CS) and Pseudo Cushing's syndrome, it is customary to use a test that is conducted by cortisol suppression with low-dose dexamethasone, followed by the administration of corticotropin releasing hormone (Dex-CRH test). In children with severe obesity, Dex-CRH test has shown a specificity of 55%. The aim of current study was to evaluate the specificity of Dex-CRH test in morbid obese adults. METHODS: The study included a total of 19 subjects with a body mass index (BMI) equal or higher than 40kg/m(2). In all subjects Dex-CRH test was performed, and 24h urinary free cortisol was collected prior the test and during the second day of dexamethasone administration (2nd-day-UFC). RESULTS: BMI was 45.1+/-4.6kg/m(2) and 45.7+/-3.3kg/m(2) in women and men, respectively. 14 subjects underwent bariatric surgery. No subject had surgical or perioperative complications and surgically treated subjects had mean body weight loss of 46.5+/-16.6kg. All except for 2 subjects had normal Dex-CRH test, as 15-min cortisol falling below 1.4MUg/dl. During follow-up, no subject gained additional weight, neither developed signs of CS. 15-min-cortisol concentration of 1.4MUg/dl revealed a specificity of 89% and 2nd-day-UFC of 16MUg/24h showed a specificity of 100%. CONCLUSIONS: Morbid obesity in adults seems not to comprise a significant confounder in Dex-CRH test, and 15-min-cortisol concentration of 1.4MUg/dl had a higher specificity than previously reported in obese children. PMID- 26277696 TI - Radioembolization as a Salvage Therapy for Heavily Pretreated Patients With Colorectal Cancer Liver Metastases: Factors That Affect Outcomes. AB - BACKGROUND: In this study we assessed the efficacy and factors that affect outcomes of radioembolization (RE) using yttrium-90 resin microspheres in patients with unresectable and chemorefractory colorectal cancer liver metastases (CLM). PATIENTS AND METHODS: After an institutional review board waiver of approval, a review of a Health Insurance Portability and Accountability Act registered, prospectively created and maintained database was performed. Data on patient demographic and disease characteristics, RE treatment parameters, and additional treatments were evaluated for significance in predicting overall survival (OS) and liver progression-free survival (LPFS). Complications were evaluated according to the National Cancer Institute Common Terminology Criteria for adverse events. RESULTS: From September 2009 to September 2013, 53 patients underwent RE at a median of 35 months after CLM diagnosis. Median OS was 12.7 months. Multivariate analysis showed that carcinoembryonic antigen levels at the time of RE >= 90 ng/mL (P = .004) and microscopic lymphovascular invasion of the primary (P = .002) were independent predictors of decreased OS. Median LPFS was 4.7 months. At 4 to 8 and 12 to 16 weeks after RE, most patients (80% and 61%, respectively) according to Response Evaluation Criteria in Solid Tumors (RECIST) had stable disease; additional evaluation using PET Response Criteria in Solid Tumors (PERCIST) led to reclassification in 77% of these cases (response or progression). No deaths were noted within the first 30 days. Within the first 90 days after RE, 4 patients (8%) developed liver failure and 5 patients (9%) died, all with evidence of disease progression. CONCLUSION: RE in the salvage setting was well-tolerated, and permitted the administration of additional therapies and led to a median OS of 12.7 months. Evaluation using PERCIST was more likely than RECIST to document response or progression compared with the baseline assessment before RE. PMID- 26277695 TI - A side-by-side comparison of T cell reactivity to fifty-nine Mycobacterium tuberculosis antigens in diverse populations from five continents. AB - We compared T cell recognition of 59 prevalently recognized Mycobacterium tuberculosis (MTB) antigens in individuals latently infected with MTB (LTBI), and uninfected individuals with previous BCG vaccination, from nine locations and populations with different HLA distribution, MTB exposure rates, and standards of TB care. This comparison revealed similar response magnitudes in diverse LTBI and BCG-vaccinated cohorts and significant correlation between responses in LTBIs from the USA and other locations. Many antigens were uniformly recognized, suggesting suitability for inclusion in vaccines targeting diverse populations. Several antigens were similarly immunodominant in LTBI and BCG cohorts, suggesting applicability for vaccines aimed at boosting BCG responses. The panel of MTB antigens will be valuable for characterizing MTB-specific CD4 T cell responses irrespective of ethnicity, infecting MTB strains and BCG vaccination status. Our results illustrate how a comparative analysis can provide insight into the relative immunogenicity of existing and novel vaccine candidates in LTBIs. PMID- 26277698 TI - Accuracy of resting metabolic rate prediction in overweight and obese Australian adults. AB - OBJECTIVES: Predictive resting metabolic rate (RMR) equations in Australian populations are at least 10 years old, focused on males and do not commonly use overweight and obese weight categorisation. The aim of this study was to measure RMR via indirect calorimetry in overweight and obese Australian adults to develop population specific predictive equations and compare with other well-known international equations (Mifflin-St. Jeor, Owen and WHO/FAO/UNU). METHODS: Retrospective data from 278 participants (154 males, 124 females: 37% overweight, 63% obese) who had attended a weight management clinic were used to develop predictive RMR equations. These were then validated against another sample (from the same clinic) of 297 participants (150 males, 147 females: 47% overweight, 53% obese), and their accuracy compared with known standard equations. RESULTS: For the prediction sample, weight, BMI, resting VO2 and measured RMR were significantly greater in the obese than overweight. Using the validation sample, the predictive equations met a +/-10% of measured RMR criterion 42% (females), 41% (total sample) and 40% (males) of the time. Prediction accuracy was not improved by using specific overweight and obese weight category equations, or by applying the known standard equations from the literature. CONCLUSIONS: In our sample of overweight and obese adults, RMR prediction to within +/-10% of the measured value was only accurate ~40% of the time, regardless of gender and weight classification. In clinical weight management settings direct measures of RMR should be made wherever possible. PMID- 26277699 TI - Breaststroke swimmers moderate internal work increases toward the highest stroke frequencies. AB - A model to predict the mechanical internal work of breaststroke swimming was designed. It allowed us to explore the frequency-internal work relationship in aquatic locomotion. Its accuracy was checked against internal work values calculated from kinematic sequences of eight participants swimming at three different self-chosen paces. Model predictions closely matched experimental data (0.58 +/- 0.07 vs 0.59 +/- 0.05 J kg(-1)m(-1); t(23)=-0.30, P=0.77), which was reflected in a slope of the major axis regression between measured and predicted total internal work whose 95% confidence intervals included the value of 1 (beta=0.84, [0.61, 1.07], N=24). The model shed light on swimmers ability to moderate the increase in internal work at high stroke frequencies. This strategy of energy minimization has never been observed before in humans, but is present in quadrupedal and octopedal animal locomotion. This was achieved through a reduced angular excursion of the heaviest segments (7.2 +/- 2.9 degrees and 3.6 +/- 1.5 degrees for the thighs and trunk, respectively, P<0.05) in favor of the lightest ones (8.8 +/- 2.3 degrees and 7.4 +/- 1.0 degrees for the shanks and forearms, respectively, P<0.05). A deeper understanding of the energy flow between the body segments and the environment is required to ascertain the possible dependency between internal and external work. This will prove essential to better understand swimming mechanical cost determinants and power generation in aquatic movements. PMID- 26277700 TI - Effect of non-Newtonian fluid properties on bovine sperm motility. AB - The swimming process by which mammal spermatozoa progress towards an egg within the reproductive organs is important in achieving successful internal fertilization. The viscosity of oviductal mucus is more than two orders of magnitude greater than that of water, and oviductal mucus also has non-Newtonian properties. In this study, we experimentally observed sperm motion in fluids with various fluid rheological properties and investigated the influence of varying the viscosity and whether the fluid was Newtonian or non-Newtonian on the sperm motility. We selected polyvinylpyrrolidone and methylcellulose as solutes to create solutions with different rheological properties. We used the semen of Japanese cattle and investigated the following parameters: the sperm velocity, the straight-line velocity and the amplitude from the trajectory, and the beat frequency from the fragellar movement. In a Newtonian fluid environment, as the viscosity increased, the motility of the sperm decreased. However, in a non Newtonian fluid, the straight-line velocity and beat frequency were significantly higher than in a Newtonian fluid with comparable viscosity. As a result, the linearity of the sperm movement increased. Additionally, increasing the viscosity brought about large changes in the sperm flagellar shape. At low viscosities, the entire flagellum moved in a curved flapping motion, whereas in the high viscosity, only the tip of the flagellum flapped. These results suggest that the bovine sperm has evolved to swim toward the egg as quickly as possible in the actual oviduct fluid, which is a high-viscosity non-Newtonian fluid. PMID- 26277701 TI - Omega-3-fatty acid adds to the protective effect of flax lignan concentrate in pressure overload-induced myocardial hypertrophy in rats via modulation of oxidative stress and apoptosis. AB - Objective of the present investigation was to study the effect of the flax lignan concentrate (FLC) and Omega-3-fatty acid (O-3-FA) on myocardial apoptosis, left ventricular (LV) contractile dysfunction and electrocardiographic abnormalities in pressure overload-induced cardiac hypertrophy. The rats were divided into five groups such as sham, aortic stenosis (AS), AS+FLC, AS+O-3-FA and AS+FLC+O-3-FA. Cardiac hypertrophy was produced in rats by abdominal aortic constriction. The rats were treated with FLC (400mg/kg, p.o.), O-3-FA (400mg/kg, p.o.) and FLC+O-3 FA orally per day for four weeks. The LV function, myocardial apoptosis, and oxidative stress were quantified. FLC+O-3-FA treatment significantly reduced hemodynamic changes, improved LV contractile dysfunction, reduced cardiomyocyte apoptosis and cellular oxidative stress. Moreover, it significantly up-regulated the VEGF expression and decreased TNF-alpha level in serum. The histological analysis also revealed that FLC+O-3-FA treatment markedly preserved the cardiac structure and inhibited interstitial fibrosis. In conclusion, FLC+O-3-FA treatment improved LV dysfunction, inhibited cardiomyocyte apoptosis, improved myocardial angiogenesis, conserved activities of membrane-bound phosphatase enzymes and suppressed inflammation through reduced oxidative stress in an additive manner than FLC alone and O-3-FA alone treatment in pressure overload induced cardiac hypertrophy. PMID- 26277702 TI - Hard-Wired Bias: How Even Double-Blind, Randomized Controlled Trials Can Be Skewed From the Start. PMID- 26277703 TI - Contrast-enhanced ultrasonographic characteristics of the diseased canine prostate gland. AB - The work was carried out on a total of 26 male dogs that on the basis of clinical examination, prostate ultrasound and prostate biopsy, were divided prospectively into four groups: (1) normal dogs (control group; n = 8); (2) dogs with benign prostatic hyperplasia (group BPH; n = 8); (3) dogs suffering from prostatitis (group prostatitis; n = 4); (4) dogs with prostatic tumors (group tumors; n = 6). The examination of the prostate by means of contrast medium and dedicated ultrasound system allowed a detailed qualitative and quantitative analysis of prostatic vessels in normal and diseased conditions, enabling the detection and characterization of different disease states, and quantification of parameters such as peak intensity of perfusion (%), arrival time of the contrast medium to its maximum value of video intensity (time to peak [TTP; seconds]), regional blood volume, regional blood flow, and mean transit time (MTT [seconds]). The hemodynamic indices TTP (P < 0.01) and MTT (P < 0.001) of diseased prostate groups were significantly lower than those in the normal prostate group although there were no differences among diseases. Optimal cutoff values were 31 seconds (Sensitivity: 72%; Specificity: 88%) and 47 seconds (Sensitivity: 100%; Specificity: 88%) while area under receiver operating characteristic curves were 0.86 (P < 0.01) and 0.97 (P < 0.01) for TTP and MTT, respectively. The qualitative evaluation of vascular patterns showed differences between normal and diseased prostate glands. The latter were characterized by an alteration of the normal vascular appearance consisting of loss of the subcapsular arterioles and lack of a centripetal vascular pattern. The qualitative aspect of the study highlighted the different vascular architecture between BPH, prostatitis, adenocarcinoma, and lymphoma. This study shows how contrast-enhanced ultrasound represents a valid and noninvasive method for highlighting and characterizing prostatic vasculature. Furthermore, it allows the operator to obtain qualitative and quantitative data that are useful for the diagnosis of selected prostatic diseases. In conclusion, contrast-enhanced ultrasound can be a valuable noninvasive diagnostic tool to improve the diagnostic accuracy of prostate diseases in the dog. PMID- 26277704 TI - Sperm selection in the female mammalian reproductive tract. Focus on the oviduct: Hypotheses, mechanisms, and new opportunities. AB - Research over the past 3 decades has caused a major shift in the way that the oviduct, or fallopian tube, is perceived. Previously, it was regarded as little more than the anatomic site for fertilization, where spermatozoa and oocytes meet as they travel in opposite directions. However, this view has been radically altered by the realization that both spermatozoa and oocytes elicit changes in the biochemical composition of oviductal fluid through the induction of novel gene expression. Moreover, it has also been shown that only a privileged sperm population, selected on the basis of multiple criteria, is permitted to enter the oviduct, where they are subjected to even more selection processes that control their motility and capacitation status, thus either inhibiting or facilitating their progress toward the oocyte. Even more recently, it has become apparent that the oviduct has some ability to differentiate the genetic signatures of X- and Y bearing spermatozoa. Although how exactly this is achieved is unknown, it prompts us to speculate that the oviduct may also be capable of distinguishing other genetically encoded properties of individual spermatozoa and that there must ultimately be a huge payoff in terms of selective animal breeding. PMID- 26277705 TI - Lifestyle Choices Fuel Epidemics of Diabetes and Cardiovascular Disease Among Asian Indians. AB - Within the next 15years, India is projected to overtake China as the world's most populous nation. Due to the rapid pace of urbanization and modernization fueling population growth, in conjunction with a genetic predisposition to insulin resistance, India is suffering a rising epidemic of non-communicable diseases (NCDs), including coronary artery disease (CAD), type 2 diabetes mellitus (T2DM), and stroke. In addition to the genetic predisposition, major negative lifestyle factors are contributing to the alarming outbreak of cardiovascular disease (CVD) among the Asian Indian population; these factors include: 1) a diet high in added sugar, refined grains and other processed foods, 2) physical inactivity, 3) vitamin D deficiency (VDD), and 4) smoking/pollution. These risk factors are all highly modifiable, and steps to improve these issues should be taken urgently to avoid a worsening NCD crisis among the inhabitants of the South Asian subcontinent as well as for people with Asian Indian ethnicity worldwide. PMID- 26277706 TI - Novel Antiplatelet Agents: The Current State and What Is Coming Down the Pike. AB - Antiplatelet therapy is the cornerstone of treatment for patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). Despite the use of dual antiplatelet therapy with aspirin and clopidogrel, a considerable number of patients still experience atherothrombotic events, which may be explained at least in part by inadequate platelet inhibition induced by this treatment regimen. This underscores the need for more potent antithrombotic strategies for the acute and long-term treatment of ischemic complications, especially in high-risk patients. These include novel generation P2Y12 receptor antagonists, such as prasugrel, ticagrelor and cangrelor, or adjunctive antiplatelet agents targeting different pathways, such as the thrombin protease activated receptors-1 receptor inhibitor vorapaxar. Moreover, since ischemic events accrue over time after an acute event, prolonging intensified antiplatelet therapy beyond 1-year has also been investigated. This manuscript provides an overview on the current status and future directions of antithrombotic therapies for the treatment of patients with ACS or treated with PCI, mainly focusing on novel agents. PMID- 26277707 TI - Enhanced Hydrogen Generation from Formic Acid by Half-Sandwich Iridium(III) Complexes with Metal/NH Bifunctionality: A Pronounced Switch from Transfer Hydrogenation. AB - By switching the catalytic function from transfer hydrogenation based on the metal/NH bifunctionality, facile dehydrogenation of formic acid was achieved by amido- and hydrido(amine)-Ir complexes derived from N-triflyl-1,2 diphenylethylenediamine (TfDPEN) at ambient temperature even in the absence of base additives. Further acceleration was observed by the addition of water, leading to a maximum turnover frequency above 6000 h(-1). A proton-relay mechanism guided by the protic amine ligand and water is postulated for effective protonation of metal hydrides. PMID- 26277708 TI - Targeting the platelet-derived growth factor signalling in cardiovascular disease. AB - Over 40 years of studies on platelet-derived growth factors (PDGFs) and their receptors, the molecular mechanisms and functional roles of PDGFs in the development of embryos and human diseases, especially in cancer, are gradually being unravelled. PDGF-BB was approved by the United States Food and Drug Administration for promoting wound healing, while imatinib, which selectively inhibits tyrosine kinase activity of PDGF receptors (PDGFR), has been prescribed to treat patients with gastrointestinal stromal tumor and chronic eosinophilic leukaemia. However, much less often have these drugs been studied in relation to cardiovascular diseases. This brief review mainly describes the role of PDGF signalling in cardiovascular pathogenesis such as atherosclerosis, pulmonary arterial hypertension, diabetes, angiogenesis and inflammation with an emphasis on how PDGFs function in these situations and what components might serve as potential therapeutic targets against cardio-metabolic dysfunction. PMID- 26277709 TI - [Study of 11 new cases of Kawasaki disease Congolese]. AB - Kawasaki's disease (KD) is a rarely described entity in Africa. The purpose of this work is to describe the clinical, biological and evolutionary aspects of KD in the Congolese child. This is a retrospective study of 11 cases of KD collected from 2003 to 2014 at the University Hospital of Brazzaville. The diagnosis was based on the criteria proposed by the Mucocutaneous Lymph Node Syndrome Research Commitee and validated by the Center for Disease Control grouping the major criteria originally described by Kawasaki and updated by the American Heart Association. The sex-ratioM/F was 2.7 and the mean age of 16.5 +/- 5.9 months (range 9 to 43 months). The average intake time was 12.8 +/- 5.9 days (range 6 and 30). In nine cases there was a complete form. The symptoms began with an invasion of the upper airway in 8 cases. Achieving oropharyngeal was in the form of oral enanthema with strawberry tongue and / or angular cheilitis; it was associated with perineal erythema in 7 cases. Reaching the end realized swelling and/or redness and / or peeling finger gloves or flap toes. The latter occurred at an average of 11 +/- 3.5 days (range 8 to 16) after the start of the fever. The treatment with acetylsalicylic acid administered to all children, began within varying between 4 and 15 days of admission. The defervescence was obtained after 5.3 +/- 2.6 days (range 4 to 11). The average hospital stay was 16.6 +/- 9.7 days (range: 11 to 25 days). The evolution after discharge was considered favorable in all cases. However, no control echocardiography was performed. KD remains an ubiquitous condition but with a variable incidence from one continent to another. The arrival of the twodimensional ultrasound should enable the systematic investigation of coronary abnormalities to catch up unnoticed past cases but also to prevent complications related there. PMID- 26277710 TI - [Blinding trachoma: results of a prevalence survey in 8 health districts in CAR]. AB - Support of visual disabilities in terms of preventive and curative treatment, is a priority for public health in Central African Republic. The lack of recent and reliable data on ocular pathologies in general including trachoma particularly, has led health authorities, in collaboration with partners to undertake an epidemiological investigation to determine the mapping. This study was designed to assess the importance of endemicity in the most sensitive groups within population, including children of 1 to 9 years old. Eight from sixteen health districts in the country, were selected for this survey as a first step. The data collected will assess the real needs in medical and surgical care to develop an appropriate strategic plan of support for this condition on a large scale. This is a cross-sectional descriptive survey carried out in one month, from November 23 to December 26, 2011 in eight health prefectures of the country. The sampling frame was the population of eight health districts. The exhaustive list of villages and demographic data from the national census conducted in December 2003, adjusted by the rate of annual increase of 2.5%has been used. The administrative headquarters of the places of the visited districts leaders were excluded from the sampling frame. A random survey in clusters at two levels made from formed bases. Twenty villages (clusters) in each health district have been drawn according to the proportional probability to the size of the totals cumulative. 12,800 children of both sexes, aged 1 to 9 years have been identified in this investigation and 11,287 were actually examined, or 88.2 %, sex ratio is significantly 1.11. The proportion by age group of the children sampled is stackable to the general population. 26.9 % of TF and 5.9 % TI have been diagnosed. Six from eight districts surveyed are endemic. Three of them had respectively rates of 32.3 %, 47.1 % and 54.3 %. PMID- 26277711 TI - Selective intracellular drug delivery from pH-responsive polyion complex micelle for enhanced malignancy suppression in vivo. AB - The pH-triggered intracellular drug delivery platforms have attracted great interest in malignancy therapy. Herein, a pH-responsive polyion complex (PIC) micelle from anionic acid-sensitive methoxy poly(ethylene glycol)-block poly(N(epsilon)-((1-carboxy-cis-cyclohexene)-2-carbonyl)-L-lysine) (mPEG-b-PCLL) and cationic doxorubicin (DOX), a model anthracycline antitumor drug, was constructed by electrostatic interaction for directional intracellular drug delivery in malignancy chemotherapy. The PIC micelle kept constant diameter at physiological condition (i.e., pH 7.4), while gradually swelled and finally disassembled at mimicking intratumoral pH (i.e., 6.8) and especially intracellular endo/lysosomal pH (i.e., 5.5). The DOX release from the PIC micelle at pH 7.4 was slow, whereas obviously accelerated at the intracellular acidic condition of pH 5.5. These results should be related to the rapid cleavage of the side amide bond of mPEG-b-PCLL in an acidic environment. The PIC micelle exhibited satisfactory tumor suppression toward the H22 hepatoma-bearing BALB/c mouse model compared with free DOX, which was demonstrated by the upregulated tumor inhibition rate, and the increased necrotic and apoptosis areas in tumor tissue. Furthermore, the enhanced security was also observed in the PIC micelle group in relation to that of free DOX. The above results strongly supported that the acid-sensitive PIC micelle was promising for selective intracellular drug delivery along with upregulated malignancy inhibition. PMID- 26277712 TI - Combination of nanoparticles with photothermal effects and phase-change material enhances the non-invasive transdermal delivery of drugs. AB - We describe a promising non-invasive transdermal delivery system comprising block copolymer composite micelles that contained a phase-change material (PCM), photothermal Au nanoparticles (AuNPs), and hydrophobic drugs in the core. To minimize cell toxicity, we developed block copolymer micelles with a poly(E caprolactone) (PCL) biodegradable core and a hyperbranched polyglycol (hbPG) shell. The hbPG block formed micelles at a low-molecular-weight fraction of a low molecular-weight block copolymer. The composite micelles showed excellent biocompatibility with cell viability at high concentrations. Visible light irradiation (lambda=520 nm) of the composite micelles induced the photothermal effects of the AuNPs and melting of the PCM (lauric acid); hence, the drugs were released along with the PCM liquid. The release rate was controlled by the light intensity. Based on in vitro and in vivo skin penetration studies, the skin permeability of the drug remarkably improved under mild light irradiation (18 J/cm(2)) that was much lower than the dose that causes skin damage. PMID- 26277713 TI - Nano-hydroxyapatite-coated metal-ceramic composite of iron-tricalcium phosphate: Improving the surface wettability, adhesion and proliferation of mesenchymal stem cells in vitro. AB - Thin radio-frequency magnetron sputter deposited nano-hydroxyapatite (HA) films were prepared on the surface of a Fe-tricalcium phosphate (Fe-TCP) bioceramic composite, which was obtained using a conventional powder injection moulding technique. The obtained nano-hydroxyapatite coated Fe-TCP biocomposites (nano-HA Fe-TCP) were studied with respect to their chemical and phase composition, surface morphology, water contact angle, surface free energy and hysteresis. The deposition process resulted in a homogeneous, single-phase HA coating. The ability of the surface to support adhesion and the proliferation of human mesenchymal stem cells (hMSCs) was studied using biological short-term tests in vitro. The surface of the uncoated Fe-TCP bioceramic composite showed an initial cell attachment after 24h of seeding, but adhesion, proliferation and growth did not persist during 14 days of culture. However, the HA-Fe-TCP surfaces allowed cell adhesion, and proliferation during 14 days. The deposition of the nano-HA films on the Fe-TCP surface resulted in higher surface energy, improved hydrophilicity and biocompatibility compared with the surface of the uncoated Fe TCP. Furthermore, it is suggested that an increase in the polar component of the surface energy was responsible for the enhanced cell adhesion and proliferation in the case of the nano-HA-Fe-TCP biocomposites. PMID- 26277714 TI - Recognition of Rhodobacter sphaeroides by microcontact-imprinted poly(ethylene-co vinyl alcohol). AB - The immobilization of cells or microorganisms is important for bioseparations, in bioreactors producing cellular metabolites, and as receptors for biosensing. Cell imprinted polymers (CIPs) have been shown to have cavities with complementary shapes and also high affinities for the template cells or microorganisms. However, the effects of binding to CIPs on gene expression are only beginning to be studied. In this work, the purple bacteria Rhodobacter sphaeroides was employed as a model for the imprinting of microorganisms. R. sphaeroides was first adsorbed on a glass slide as the stamp and then microcontact-imprinted onto poly(ethylene-co-vinyl alcohol), EVAL. The surfaces of the R. sphaeroides imprinted (RsIPs) and non-imprinted (NIPs) EVAL thin films were examined by Raman spectrometry and scanning electron microscopy. The expression of the nitrogenase (nitrogen fixation, nifH) gene of R. sphaeroides adsorbed on both the RsIPs and NIPs EVAL thin films was also measured by the quantitative reverse transcription polymerase chain reaction (qRT-PCR); cells grown on imprinted polymer showed dramatic differences in gene expression compared to controls. PMID- 26277715 TI - Pluronic/gelatin composites for controlled release of actives. AB - This paper describes the preparation and the release properties of composite materials based on Pluronic F127 and gelatin hydrogels, which could be of interest in the field of enteral nutrition or drug administration. The composites were prepared by exploiting the opposite responsivity to temperature of a 20% w/w Pluronic F127 aqueous solution (critical gelation temperature around 23 degrees C) and gelatin (gel-sol temperature transition around 30 degrees C). Pluronic domains dispersed within a gelatin matrix were obtained by injecting cold Pluronic F127 solutions inside hot gelatin solutions, while homogenizing either with a magnetic stirrer or a high-energy mechanical disperser. Calorimetry indicates that the composites retain the individual gelling properties of Pluronic and gelatin. Different releasing properties were obtained as a function of the preparation protocol, the temperature and the pH. The release profiles have been studied by a Weibull analysis that clearly points out the dominating role of gelatin at 25 degrees C. At 37 degrees C the release accounts for a combined effect from both Pluronic F127 and gelatin, showing a more sustained profile with respect to gelatin hydrogels. This behavior, together with the ability of Pluronic F127 to upload both hydrophilic and hydrophobic drugs and flavors, makes these innovative composite materials very good candidates as FDA approved carriers for enteral administration. PMID- 26277716 TI - Enhancing the water dispersibility of paclitaxel by complexation with hydrophobic peptides. AB - The complex between paclitaxel (Ptx) and a peptide mixture (Pep) was prepared to enhance of the water-dispersibility of Ptx. Pep was prepared by enzymatic hydrolysis of casein, followed by fractionation using ammonium sulfate precipitation and ultrafiltration. The Ptx and Pep complex (Ptx-Pep) was prepared by mixing an ethanol solution of Ptx and an aqueous solution of Pep followed by lyophilization. The water dispersibility test of Ptx-Pep prepared using different fractions of Pep demonstrated that a fraction (Pep-A), containing relatively hydrophobic peptides with high molecular weights, was effective in enhancing the water dispersibility of Ptx. The sequences of the major peptides in Pep-A were identified by matrix-assisted laser desorption/ionization time-of-flight/time-of flight mass spectrometry with "LIFT" technique. The water dispersibility of the complex between Ptx and Pep-A (Ptx-Pep-A) was independent of pH, even though it is positively or negatively charged under strongly acidic and neutral conditions. As the particle size of Ptx-Pep-A in aqueous media was 147-215 nm, Ptx-Pep-A was present as a hydrocolloidal material in aqueous media. PMID- 26277717 TI - A tubular gelatin scaffold capable of the time-dependent controlled release of epidermal growth factor and mitomycin C. AB - A tubular gelatin scaffold for the time-dependent controlled release of epidermal growth factor (EGF) and mitomycin C (MMC) was fabricated. EGF was incorporated using silk fibroin carriers, and MMC was planted using polylactide (PLA) microspheres. The relationship between scaffold properties and crosslinking degrees was evaluated. As the crosslinking degree was increased from 23.7% to 65.3%, the mechanical properties of the scaffold obviously improved, and the compressive modulus increased to approximately 65kPa. The mass degradation of the scaffold was also controlled from 9 days to approximately 1 month. In vitro release tests indicated that the scaffold mainly released EGF in the early period and MMC in the later period. Urethral epithelial cells (UECs) and urethral scar derived fibroblast cells (UFCs) were coseeded in the scaffold at a ratio of 1:1. After 9 days of coculture, immunostaining results displayed that the proportion of UECs continuously increased to approximately 71%. These changes in cell proportion were confirmed by the results of Western blot analysis. Therefore, the scaffold promoted the growth but inhibited the regeneration of UFCs. This scaffold for time-dependent controlled release of multiple biofactors may be potentially useful in urethral reconstruction and other tissue engineering studies. PMID- 26277718 TI - An evaluation of the potential yield of indium recycled from end-of-life LCDs: A case study in China. AB - With the advances in electronics and information technology, China has gradually become the largest consumer of household appliances (HAs). Increasingly, end-of life (EOL) HAs are generated in China. EOL recycling is a promising strategy to reduce dependence on virgin production, and indium is one of the recycled substances. The potential yield of indium recycling has not been systematically evaluated in China thus far. This paper estimates the potential yield of recycled indium from waste liquid crystal displays (LCDs) in China during the period from 2015 to 2030. The quantities of indium that will be used to produce LCDs are also predicted. The estimates focus on the following three key LCD waste sources: LCD TVs, desktop computers and portable computers. The results show that the demand for indium will be increasing in the near future. It is expected that 350 tonnes of indium will be needed to produce LCDs in China in 2035. The indium recycled from EOL LCDs, however, is much less than the demand and only accounts for approximately 48% of the indium demand. The sustainable index of indium is always less than 0.5. Therefore, future indium recycling efforts should focus on the development of recycling technology and the improvement of the relevant policy. PMID- 26277719 TI - Withdrawal of the circular economy package: A wasted opportunity or a new challenge? PMID- 26277720 TI - Light- and temperature-regulated BjAPY2 may have a role in stem expansion of Brassica juncea. AB - Tuber mustard (Brassica juncea (L.) Czern. et Coss. var. tumida Tsen et Lee) is an important vegetable crop with a characteristic of expanded stem that is edible. The underlying molecular mechanism of the stem expansion is not well understood. Here, we reported that a total of 51 differentially expressed fragments (DEFs) with three expression patterns during stem expansion of tuber mustard were identified by cDNA-AFLP analysis. Among the DEFs, DEF11 with high homology to Arabidopsis thaliana apyrase 2 (AtAPY2) that encodes an enzyme with ATPase and ADPase activity was development- and tissue-specific. DEF11 was thus renamed as BjAPY2. The expression levels of BjAPY2 increased with the stem expression and were the highest at stage IV, a developmental stage at which the stem expanded most rapidly. In contrast, the BjAPY2 expression levels in leaves were much lower and remained unchanged during leaf development and expansion, suggesting that BjAPY2 was closely associated with the expansion of stems but not of leaves in the tuber mustard. Interestingly, the expression of BjAPY2 was higher in the mustard under short-day (SD) photoperiod (8 h/16 h) than that under long-day (LD) photoperiod (16 h/8 h); similarly, the transcript levels of BjAPY2 were higher in the mustard grown at low temperature (14 degrees C/12 degrees C) than that at high temperature (26 degrees C /24 degrees C). The SD photoperiod and low temperature were two environmental conditions that favored the mustard stem expansion. Further cloning and analysis of the promoter region of BjAPY2 revealed that there were indeed several types of motifs in the promoter region, including the light and temperature responsive elements. These results suggested that BjAPY2 might play an important role during the stem expansion of the tuber mustard. PMID- 26277722 TI - Germin-like protein 2 gene promoter from rice is responsive to fungal pathogens in transgenic potato plants. AB - Controlled transgene expression via a promoter is particularly triggered in response to pathogen infiltration. This is significant for eliciting disease resistant features in crops through genetic engineering. The germins and germin like proteins (GLPs) are known to be associated with plant and developmental stages. The 1107-bp Oryza sativa root GLP2 (OsRGLP2) gene promoter fused to a beta-glucuronidase (GUS) reporter gene was transformed into potato plants through an Agrobacterium-mediated transformation. The OsRGLP2 promoter was activated in response to Fusarium solani (Mart.) Sacc. and Alternaria solani Sorauer. Quantitative real-time PCR results revealed 4-5-fold increase in promoter activity every 24 h following infection. There was a 15-fold increase in OsRGLP2 promoter activity after 72 h of F. solani (Mart.) Sacc. treatment and a 12-fold increase observed with A. solani Sorauer. Our results confirmed that the OsRGLP2 promoter activity was enhanced under fungal stress. Furthermore, a hyperaccumulation of H2O2 in transgenic plants is a clear signal for the involvement of OsRGLP2 promoter region in the activation of specific genes in the potato genome involved in H2O2-mediated defense response. The OsRGLP2 promoter evidently harbors copies of GT-I and Dof transcription factors (AAAG) that act in response to elicitors generated in the wake of pathogen infection. PMID- 26277721 TI - Caspases in plants: metacaspase gene family in plant stress responses. AB - Programmed cell death (PCD) is an ordered cell suicide that removes unwanted or damaged cells, playing a role in defense to environmental stresses and pathogen invasion. PCD is component of the life cycle of plants, occurring throughout development from embryogenesis to the death. Metacaspases are cysteine proteases present in plants, fungi, and protists. In certain plant-pathogen interactions, the PCD seems to be mediated by metacaspases. We adopted a comparative genomic approach to identify genes coding for the metacaspases in Viridiplantae. We observed that the metacaspase was divided into types I and II, based on their protein structure. The type I has a metacaspase domain at the C-terminus region, presenting or not a zinc finger motif in the N-terminus region and a prodomain rich in proline. Metacaspase type II does not feature the prodomain and the zinc finger, but has a linker between caspase-like catalytic domains of 20 kDa (p20) and 10 kDa (p10). A high conservation was observed in the zinc finger domain (type I proteins) and in p20 and p10 subunits (types I and II proteins). The phylogeny showed that the metacaspases are divided into three principal groups: type I with and without zinc finger domain and type II metacaspases. The algae and moss are presented as outgroup, suggesting that these three classes of metacaspases originated in the early stages of Viridiplantae, being the absence of the zinc finger domain the ancient condition. The study of metacaspase can clarify their assignment and involvement in plant PCD mechanisms. PMID- 26277723 TI - Influences on Healthy-Eating Decision Making in Latino Adolescent Children of Migrant and Seasonal Agricultural Workers. AB - INTRODUCTION: Latino children demonstrate high rates of unhealthy weight, and children of Latino migrant and seasonal agricultural workers are heavier than their Latino peers. METHOD: This one-group, cross-sectional, mixed-methods pilot study explored healthy-eating decision making with 12- to 14-year-olds recruited from a Midwest summer migrant education program. Demographics, decision-making, self-efficacy, and social support survey instruments were used, along with gender specific focus groups. RESULT: In the convenience sample, which included 24 participants, students felt varying degrees of uncertainty when choosing healthy foods in social situations, and 67% made poor-quality decisions. Parents offered greater support for healthy eating compared with friends. Qualitative analyses identified three themes: healthy decision making includes fruits, vegetables, and physical activity; mothers have influence over health and healthy decisions; and friends encourage unhealthy food choices. DISCUSSION: Influences on healthy eating decision making in Latino adolescent children of migrant and seasonal agricultural workers, which were previously missing from the literature, were identified. Future research includes development of interventions to assist these adolescents with healthy-eating decision making. PMID- 26277724 TI - Testosterone replacement attenuates cognitive decline in testosterone-deprived lean rats, but not in obese rats, by mitigating brain oxidative stress. AB - Testosterone replacement improves metabolic parameters and cognitive function in hypogonadism. However, the effects of testosterone therapy on cognition in obese condition with testosterone deprivation have not been investigated. We hypothesized that testosterone replacement improves cognitive function in testosterone-deprived obese rats by restoring brain insulin sensitivity, brain mitochondrial function, and hippocampal synaptic plasticity. Thirty male Wistar rats had either a bilateral orchiectomy (ORX: O, n = 24) or a sham operation (S, n = 6). ORX rats were further divided into two groups fed with either a normal diet (NDO) or a high-fat diet (HFO) for 12 weeks. Then, ORX rats in each dietary group were divided into two subgroups (n = 6/subgroup) and were given either castor oil or testosterone (2 mg/kg/day, s.c.) for 4 weeks. At the end of this protocol, cognitive function, metabolic parameters, brain insulin sensitivity, hippocampal synaptic plasticity, and brain mitochondrial function were determined. We found that testosterone replacement increased peripheral insulin sensitivity, decreased circulation and brain oxidative stress levels, and attenuated brain mitochondrial ROS production in HFO rats. However, testosterone failed to restore hippocampal synaptic plasticity and cognitive function in HFO rats. In contrast, in NDO rats, testosterone decreased circulation and brain oxidative stress levels, attenuated brain mitochondrial ROS production, and restored hippocampal synaptic plasticity as well as cognitive function. These findings suggest that testosterone replacement improved peripheral insulin sensitivity and decreased oxidative stress levels, but failed to restore hippocampal synaptic plasticity and cognitive function in testosterone-deprived obese rats. However, it provided beneficial effects in reversing cognitive impairment in testosterone-deprived non-obese rats. PMID- 26277726 TI - Ambulatory Blood Pressure Monitoring in the Diagnosis, Prognosis, and Management of Resistant Hypertension: Still a Matter of our Resistance? AB - Resistant hypertension, commonly described as the failure to achieve goal blood pressure (BP) despite an appropriate regimen of three antihypertensive drugs at the maximal tolerated doses, one of which is diuretic, is increasingly recognized as an important problem of public health. Large population studies with office measurements suggest that the prevalence of resistance hypertension is approximately at 6-12 % of the general hypertensive population and 8-28 % of treated hypertensives. However, these estimations do not take into account factors of pseudo-resistance, most importantly, the white-coat effect that can be effectively ruled out with ambulatory blood pressure monitoring (ABPM). Recent studies have clearly shown that when ABPM is used, at least 30-35 % of patients labeled as "resistant hypertensives" turn out to have well-controlled BP on ambulatory basis, a finding changing entirely the estimates of prevalence of resistance hypertension and actual patient handling. Furthermore, current evidence suggests that ABPM is a much more accurate predictor of cardiovascular events in resistant hypertension compared to office BP and thus can offer a better risk stratification for these high-risk individuals. Finally, ABPM offers the potential of a better evaluation of the effect of pharmacologic and non pharmacologic therapeutic interventions. This review attempts to summarize recent evidence on the advantages of ABPM in the diagnosis, prognosis, and management of resistant hypertension. PMID- 26277725 TI - Influence of Physical Activity on Hypertension and Cardiac Structure and Function. AB - The global burden of hypertension is rising and accounts for substantial morbidity and mortality. Lifestyle factors such as diet and physical inactivity contribute to this burden, further highlighting the need for prevention efforts to curb this public health epidemic. Regular physical activity is associated with lower blood pressure, reduced cardiovascular risk, and cardiac remodeling. While exercise and hypertension can both be associated with the development of left ventricular hypertrophy (LVH), the cardiac remodeling from hypertension is pathologic with an associated increase in myocyte hypertrophy, fibrosis, and risk of heart failure and mortality, whereas LVH in athletes is generally non pathologic and lacks the fibrosis seen in hypertension. In hypertensive patients, physical activity has been associated with paradoxical regression or prevention of LVH, suggesting a mechanism by which exercise can benefit hypertensive patients. Further studies are needed to better understand the mechanisms underlying the benefits of physical activity in the hypertensive heart. PMID- 26277728 TI - Transient splenial lesion in a case with carbon monoxide poisoning: A clue supporting the excitotoxicity hypothesis? AB - Transient splenial lesions of the corpus callosum are uncommon radiologic findings seen in a number of clinical conditions. Awareness of these lesions is crucial to prevent further invasive investigation and intervention. We report a unique case of transient splenial lesion in a patient with carbon monoxide poisoning. PMID- 26277727 TI - Physiological and biochemical effects of botanical extract from Piper nigrum Linn (Piperaceae) against the dengue vector Aedes aegypti Liston (Diptera: Culicidae). AB - The leaves of Piper nigrum L. (Piperaceae) were evaluated for chemical constituents and mosquito larvicidal activity against the larvae of Aedes aegypti. GC and GC-MS analyses revealed that the crude extracts contain 16 compounds. Thymol (20.77%) and c-elemene (10.42%) were identified as the major constituents followed by cyclohexene, 4-ethenyl-4-methyl-3-(1-methylethenyl)-1-(1 methylethyl)-, (3R-trans) (7.58%), 4,6-octadienoic acid, 2-acetyl-2-methyl-, ethyl ester (6.98), 2(3H)-furanone, 3,4-bis(1,3-benzodioxol-5-ylmethyl) dihydro-, (3R-trans) (6.95%), 1-naphthalenol, 1,2,3,4,4a,7,8,8a-octahydro-1,6-dimethyl-4-(1 methylethyl)-, [1R-(1a,4a,4aa,8aa)]-(Cedreanol) (5.30%), trans-2-undecen-1-ol (4.48%), phytol (4.22%), 1,6-cyclodecadiene, 1-methyl-5-methylene-8-(1 methylethyl)-,[s-(E,E)] (3.78%) and 2,6-dimethyl-3,5,7-octatriene-2-ol, Z,Z (2.39%). Larval mortality was observed after 3 h of exposure period. The crude extract showed remarkable larvicidal activity against Ae. aegypti (LC50 = 34.97). The larvae of Ae. aegypti exposed to the P. nigrum, significantly reduced the activities of alpha- and beta-carboxylesterases and superdioxide. Further, P. nigrum extract was severely affecting the mosquito gut cellular organelles. Based on the results, the chemical constituents of crude extracts of P. nigrum can be considered as a new source of larvicide for the control of Ae. aegypti. PMID- 26277729 TI - Early postoperative cartilage evaluation by magnetic resonance imaging using T2 mapping after arthroscopic partial medial meniscectomy. AB - PURPOSE: This study was performed to quantitatively evaluate postoperative changes in cartilage by T2 mapping after arthroscopic partial medial meniscectomy. MATERIAL AND METHODS: The study enrolled 17 patients with 20 knees that underwent arthroscopic partial medial meniscectomy. MRI was performed preoperatively and at six months postoperatively, with subjects evaluated by T2 mapping of the central part of the medial condyle of the femur in the sagittal plane. Regions of interest (ROIs) were set at 10 points between the point of intersection of the anatomical axis of the femur and the articular surface of the medial condyle and posterior area approximately 90 degrees to the anatomical axis. Pre- and postoperative T2 values at each ROI were evaluated. RESULTS: Postoperative T2 values were significantly longer than preoperative values at approximately 20, 30, 40, and 50 degrees to the anatomical axis of the femur. The maximum change between pre- and postoperative T2 values was +6.65% at 30 degrees to the anatomical axis. CONCLUSIONS: Mechanical stress at positions approximately 20, 30, 40, and 50 degrees relative to the anatomical axis of the femur increased soon after arthroscopic medial meniscectomy. These findings indicate the start of degeneration, via disorganization of collagen arrays, of the articular cartilage and increased water content. PMID- 26277730 TI - Semi-automatic lung segmentation of DCE-MRI data sets of 2-year old children after congenital diaphragmatic hernia repair: Initial results. AB - In congenital diaphragmatic hernia (CDH), lung hypoplasia and secondary pulmonary hypertension are the major causes of death and severe disability. Based on new therapeutic strategies survival rates could be improved to up to 80%. However, after surgical repair of CDH, long-term follow-up of these pediatric patients is necessary. In this, dynamic contrast enhanced magnetic resonance imaging (DCE MRI) provides insights into the pulmonary microcirculation and might become a tool within the routine follow-up program of CDH patients. However, whole lung segmentation from DCE-MRI scans is tedious and automated procedures are warranted. Therefore, in this study, an approach to semi-automated lung segmentation is presented. Segmentation of the lung is obtained by calculating the cross correlation and the area under curve between all voxels in the data set and a reference region-of-interest (ROI), here the arterial input function (AIF). By applying an upper and lower threshold to the obtained maps and intersecting these, a final segmentation is reached. This approach was tested on twelve DCE MRI data sets of 2-year old children after CDH repair. Segmentation accuracy was evaluated by comparing obtained automatic segmentations to manual delineations using the Dice overlap measure. Optimal thresholds for the cross correlation were 0.5/0.95 and 0.1/0.5 for the area under curve, respectively. The ipsilateral (left) lung showed reduced segmentation accuracy compared to the contralateral (right) lung. Average processing time was about 1.4s per data set. Average Dice score was 0.7+/-0.1 for the whole lung. In conclusion, initial results are promising. By our approach, whole lung segmentation is possible and a rapid evaluation of whole lung perfusion becomes possible. This might allow for a more detailed analysis of lung hypoplasia of children after CDH. PMID- 26277731 TI - Hemodynamic monitoring and mortality. PMID- 26277732 TI - Development and preliminary test of a new plateau hyperbaric chamber. AB - OBJECTIVE: The objective of this study is to validate the performance, define its limits, and provide details on a new plateau hyperbaric chamber at 355-, 2880-, and 4532-m high altitude. METHODS: A new multiplace plateau hyperbaric chamber was designed to satisfy the needed of patients who have acute mountain sickness. Tests were conducted inside the chamber at 355-, 2880-, and 4532-m high altitude. The safely and conveniences of the new plateau hyperbaric chamber were estimated. RESULTS: Minimum pressures of the main compartment can reach up to 0.029, 0.022, and 0.02 MPa at 355-, 2880-, and 4532-m high altitude. During pressurization, there was no leak of air around the chamber. The time lag of pressure equilibration between main and buffer compartment varies from 30.3+/-2.01 to 200.5+/-5.44 seconds and between buffer compartment and ambient pressure varies from 60.2+/-4.13 to 215.9+/-6.76 seconds. CONCLUSIONS: The chamber can be applicated for acute mountain sickness treatment safety and convenience. However, further experience about animals and human within the chamber is needed to improve the hardware and establish conditions of effective utilization of this equipment in the high altitude. PMID- 26277733 TI - Response to letter to the editor "High prevalence of Takotsubo syndrome in patients admitted to the Medical Intensive Care Unit with non-cardiac illnesses" by John E. Madias, MD. PMID- 26277734 TI - Severity of polymicrobial sepsis modulates mitochondrial function in rat liver. AB - Mitochondrial dysfunction is assumed to be an important contributor to multi organ dysfunction syndrome. Here, the effects of varying degrees of sepsis on hepatic mitochondrial function were investigated. Moderate or more severe sepsis was induced in rats using a colon ascendens stent peritonitis (CASP)-model (16 G and 14 G stent respectively). Respiratory control ratio (RCR) was significantly higher in the 16 G-group and unchanged in the 14 G-group compared with healthy controls. The ADP/O ratio was similar in all groups. Our results indicate that different severities of sepsis differently influence the mitochondrial function, which could be a sign of adaptive reaction. PMID- 26277735 TI - Dual-porosity poroviscoelasticity and quantitative hydromechanical characterization of the brain tissue with experimental hydrocephalus data. AB - Hydromechanical brain models often involve constitutive relations which must account for soft tissue deformation and creep, together with the interstitial fluid movement and exchange through capillaries. The interaction of rather unknown mechanisms which produce, absorb, and circulate the cerebrospinal fluid within the central nervous system can further add to their complexity. Once proper models for these phenomena or processes are selected, estimation of the associated parameters could be even more challenging. This paper presents the results of a consistent, coupled poroviscoelastic modeling and characterization of the brain tissue as a dual-porosity system. The model draws from Biot's theory of poroviscoelasticity, and adopts the generalized Kelvin's rheological description of the viscoelastic tissue behavior. While the interstitial space serves as the primary porosity through which the bulk flow of the interstitial fluid occurs, a secondary porosity network comprising the capillaries and venous system allows for its partial absorption into the blood. The correspondence principle is used in deriving a time-dependent analytical solution to the proposed model. It allows for identical poroelastic formulation of the original poroviscoelastic problem in the Laplace transform space. Hydrocephalus generally refers to a class of medical conditions which share the ventricles enlargement as a common feature. A set of published data from induced hydrocephalus and follow up perfusion of cats' brains is used for quantitative characterization of the proposed model. A selected portion of these data including the ventricular volume and rate of fluid absorption from the perfused brain, together with the forward model solution, is utilized via an inverse problem technique to find proper estimations of the model parameters. Results show significant improvement in model predictions of the experimental data. The convoluted and coupled solution results are presented through the time-dependent plots of the ventricular volume undergoing the perfusion experiment. The plots demonstrate the intricate interplay of viscous and poroelastic diffusive time scales, and their competition in reaching the steady state response of the system. PMID- 26277736 TI - Primary papillary carcinoma in thyroglossal cysts. Case reports and literature review. AB - The thyroglossal cyst can exceptionally appear as a primary cyst carcinoma. We discuss a series of 6 adult patients, assessed for long-lasting asymptomatic suprahyoid or lateral-to-larynx mass. The images showed a heterogeneous mass invading adjacent soft tissues. Fine needle aspiration biopsy did not contribute to diagnosis. We performed a Sistrunk procedure in all cases, 3 combined with total thyroidectomy and 1 with neck dissection. The postoperative course was favourable. No additional treatment was required, without evidence of recurrence in follow-up. The management is controversial due to the limited number of cases reported. Some classifications based on size and extent have been proposed to define the surgical treatment of such cysts. PMID- 26277737 TI - Pharyngeal tuberculosis: Report of 5 cases. AB - Tuberculosis is a public health problem for many countries, whether rich or poor. Extranodal ENT locations are rare, and it prevails in the cavum in the pharyngeal region. Based on a 3-year retrospective study of 5 clinical cases, the authors aim to highlight the epidemiological, clinical, radiological, therapeutic and prognostic aspects of this disease. Clinical aspects are not specific and there is often confusion in the differential diagnosis with tumoral lesions. Positive diagnosis is guided by the clinical and the radiological findings, and confirmed by histology. PMID- 26277738 TI - [Diagnostic criteria for Meniere's disease. Consensus document of the Barany Society, the Japan Society for Equilibrium Research, the European Academy of Otology and Neurotology (EAONO), the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) and the Korean Balance Society]. AB - This paper presents diagnostic criteria for Meniere's disease jointly formulated by the Classification Committee of the Barany Society, The Japan Society for Equilibrium Research, the European Academy of Otology and Neurotology (EAONO), the Equilibrium Committee of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) and the Korean Balance Society. The classification includes 2 categories: definite Meniere's disease and probable Meniere's disease. The diagnosis of definite Meniere's disease is based on clinical criteria and requires the observation of an episodic vertigo syndrome associated with low-to medium-frequency sensorineural hearing loss and fluctuating aural symptoms (hearing, tinnitus and/or fullness) in the affected ear. Duration of vertigo episodes is limited to a period between 20 min and 12h. Probable Meniere's disease is a broader concept defined by episodic vestibular symptoms (vertigo or dizziness) associated with fluctuating aural symptoms occurring in a period from 20 min to 24h. PMID- 26277739 TI - Labyrinthine haemorrhage secondary to oral anticoagulants. PMID- 26277740 TI - The effect of spatio-temporal distance between visual stimuli on information processing in children with Specific Language Impairment. AB - The purpose of this study is to evaluate whether children with Specific Language Impairment (SLI) have a deficit in processing a sequence of two visual stimuli (S1 and S2) presented at different inter-stimulus intervals and in different spatial locations. In particular, the core of this study is to investigate whether S1 identification is disrupted due to a retroactive interference of S2. To this aim, two experiments were planned in which children with SLI and children with typical development (TD), matched by age and non-verbal IQ, were compared (Experiment 1: SLI n=19; TD n=19; Experiment 2: SLI n=16; TD n=16). Results show group differences in the ability to identify a single stimulus surrounded by flankers (Baseline level). Moreover, children with SLI show a stronger negative interference of S2, both for temporal and spatial modulation. These results are discussed in the light of an attentional processing limitation in children with SLI. PMID- 26277741 TI - The neurotoxicology of uranium. AB - The brain is a target of environmental toxic pollutants that impair cerebral functions. Uranium is present in the environment as a result of natural deposits and release by human applications. The first part of this review describes the passage of uranium into the brain, and its effects on neurological functions and cognitive abilities. Very few human studies have looked at its cognitive effects. Experimental studies show that after exposure, uranium can reach the brain and lead to neurobehavioral impairments, including increased locomotor activity, perturbation of the sleep-wake cycle, decreased memory, and increased anxiety. The mechanisms underlying these neurobehavioral disturbances are not clearly understood. It is evident that there must be more than one toxic mechanism and that it might include different targets in the brain. In the second part, we therefore review the principal mechanisms that have been investigated in experimental models: imbalance of the anti/pro-oxidant system and neurochemical and neurophysiological pathways. Uranium effects are clearly specific according to brain area, dose, and time. Nonetheless, this review demonstrates the paucity of data about its effects on developmental processes and the need for more attention to the consequences of exposure during development. PMID- 26277742 TI - Biosimilars in India. AB - Biosimilars have been defined as biotech drugs that have been shown to have comparable quality, safety and efficacy to the original product. The past decade has seen a significant increase in interest in these products from the biotech industry. Major developments have occurred with respect to establishing a regulatory path for approval of these products as well as in our understanding of how the different quality attributes of a biosimilar impact its safety and efficacy. India is globally regarded to have great potential to become a significant player in development and commercialization of biosimilars. This short communication aims to provide a brief discussion on where India is with respect to development and commercialization of biosimilars, major challenges it faces, and finally the significant role that proteomics can play in establishing analytical comparability of biosimilars.This article is part of a Special Issue entitled: Proteomics in India. PMID- 26277744 TI - Methyltrimethoxysilane (MTMS)-based silica-iron oxide superhydrophobic nanocomposites. AB - We report a facile synthesis of superhydrophobic silica-iron oxide nanocomposites via a co-precursor sol-gel process. The choice of the silica precursor (Methyltrimethoxysilane, MTMS) in combination with iron nitrate altered the pore structure dramatically. The influence of iron oxide doping on the structural properties of pristine MTMS aerogel is discussed. PMID- 26277743 TI - Dopamine D1 receptor stimulation modulates the formation and retrieval of novel object recognition memory: Role of the prelimbic cortex. AB - Previous studies have shown that dopamine D1 receptor antagonists impair novel object recognition memory but the effects of dopamine D1 receptor stimulation remain to be determined. This study investigated the effects of the selective dopamine D1 receptor agonist SKF81297 on acquisition and retrieval in the novel object recognition task in male Wistar rats. SKF81297 (0.4 and 0.8 mg/kg s.c.) given 15 min before the sampling phase impaired novel object recognition evaluated 10 min or 24 h later. The same treatments also reduced novel object recognition memory tested 24 h after the sampling phase and when given 15 min before the choice session. These data indicate that D1 receptor stimulation modulates both the encoding and retrieval of object recognition memory. Microinfusion of SKF81297 (0.025 or 0.05 MUg/side) into the prelimbic sub-region of the medial prefrontal cortex (mPFC) in this case 10 min before the sampling phase also impaired novel object recognition memory, suggesting that the mPFC is one important site mediating the effects of D1 receptor stimulation on visual recognition memory. PMID- 26277745 TI - Recent advancement of gelatin nanoparticles in drug and vaccine delivery. AB - Novel drug delivery system using nanoscale materials with a broad spectrum of applications provides a new therapeutic foundation for technological integration and innovation. Nanoparticles are suitable drug carrier for various routes of administration as well as rapid recognition by the immune system. Gelatin, the biological macromolecule is a versatile drug/vaccine delivery carrier in pharmaceutical field due to its biodegradable, biocompatible, non-antigenicity and low cost with easy availability. The surface of gelatin nanoparticles can be modified with site-specific ligands, cationized with amine derivatives or, coated with polyethyl glycols to achieve targeted and sustained release drug delivery. Compared to other colloidal carriers, gelatin nanoparticles are better stable in biological fluids to provide the desired controlled and sustained release of entrapped drug molecules. The current review highlights the different formulation aspects of gelatin nanoparticles which affect the particle characteristics like zeta potential, polydispersity index, entrapment efficacy and drug release properties. It has also given emphasis on the major applications of gelatin nanoparticles in drug and vaccine delivery, gene delivery to target tissues and nutraceutical delivery for improving the poor bioavailabity of bioactive phytonutrients. PMID- 26277746 TI - Characterization of a new family 75 chitosanase from Aspergillus sp. W-2. AB - A new chitosanase gene of glycoside hydrolase (GH) family 75, csnw2, was cloned from an isolated strain Aspergillus sp. W-2 (CGMCC7018). The mature CsnW2 protein, fused to His-tag at C-terminus, was expressed in Pichia pastoris X-33 and purified with the affinity chromatography of Ni(2+)-NTA. The novel recombinant CsnW2 showed maximal activity with chitosan at pH 6.0 and 55 degrees C. Moreover, it had good pH stability and thermostability at a broad pH range of 3.0-10.0 and a temperature range of 30-70 degrees C, respectively. The enzymatic activity of the CsnW2 could be significantly enhanced by Ca(2+), Mn(2+) and Mg(2+) at a concentration of 1mM, but strongly inhibited by Fe(2+), Zn(2+), Ge(2+), Ni(2+) and Cu(2+) above 1mM. The CsnW2 showed specific hydrolytic activity against chitosan and preferred to hydrolyze chitosan with high degree of deacetylation. The main products of chtiosan (92% deacetylation) were chitosan oligosaccharides (COS) with degree of polymerization (DP) arranging from 2 to 6. Combined with the hydrolysis of COS from DP2 to DP6, CsnW2 was considered to be an endo-acting chitosanase. PMID- 26277747 TI - Antioxidant activity and optimization of extraction of polysaccharide from the roots of Dipsacus asperoides. AB - Polysaccharide extraction from Dipsacus asperoides roots (DAP) was proved to possess strong antioxidant activities, including 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-Azobis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) radical scavenging activities, inhibiting beta-carotene bleaching and strong reducing power. Cell assay demonstrated that the crude DAP possessed antioxidant activity and were effective against H2O2-induced L02 cells injury. Then, response surface methodology (RSM) was applied to optimize the ultrasonic extraction of DAP. The optimum variables given by central composite design (CCD) were as follows: ratio of water to raw material, 38.61mL/g; ultrasonic power, 308.68W; extraction time, 38.61min; and extraction temperature, 89 degrees C. Under these conditions, the maximum yield of DAP obtained was 7.12+/-0.45%. Moreover, high performance liquid chromatography (HPLC) analysis suggested that the monosaccharide compositions of DAP contained primarily mannose, ribose, glucose, galactose, xylose and arabinose, with a molar ratio of 0.22:0.48:2.29:0.34:1.39:1.41. The results of the present study showed that DAP could be considered as potential sources of natural antioxidants. PMID- 26277748 TI - Characterization of Auricularia auricula polysaccharides and its antioxidant properties in fresh and pickled product. AB - The study planned to determine proximate composition, antioxidant activity and chemical characterization in the fruit bodies of Auricularia auricula and pickled product. Two polysaccharide fractions (AAPF, AAPP) were purified from the fruiting body of A. auricula by ethanol precipitation, deproteination and macroporous resins and were subsequently lyophilized. The results showed that AAPF consisted of five monosaccharides, including glucose, rhamnose, arabinose, mannose and galactose with a molar ratio of 16.74:1.0:1.18:1.0:1.0; in contrast, AAPP was composed of four monosaccharides, namely arabinose, mannose, galactose and xylose with the molar ratio of 15.59:1.52:4.76:1.0. AAPF and AAPP were characterized by Fourier Transform Infrared spectroscopy (FTIR), which indicated peaks at approximately 3500cm(-1) and 522.28cm(-1) in the carbohydrate region and composed of beta-glycoside linkages at the 1200-1000cm(-1) peaks. However, the antioxidant activity of AAPF demonstrated a significant result in scavenging free radicals except for DDPH. The in vitro test indicated that AAPF and AAPP have good antioxidant activity, demonstrating that A. auricula polysaccharide has immense potential as a functional food. PMID- 26277749 TI - Surface morphology of chitin highly related with the isolated body part of butterfly (Argynnis pandora). AB - This study was conducted to understand the differences in the physicochemical properties of chitin samples isolated from the wings and the other body parts except the wings (OBP) of a butterfly species (Argynnis pandora). The same isolation method was used for obtaining chitin specimens from both types of body parts. The chitin content of the wings (22%) was recorded as being much higher than the OBP (8%). The extracted chitin samples were characterized via FT-IR, TGA, XRD, SEM, and elemental analysis techniques. Results of these characterizations revealed that the chitins from both structures (wings and OBP) were very similar, except for their surface morphologies. SEM results demonstrated one type of surface morphology for the wings and four different surface morphologies for the OBP. Therefore, it can be hypothesized that the surface morphology of the chitin is highly related with the body part. PMID- 26277750 TI - Evaluation of the recombinant turkey pancreatic lipase phospholipase activity: A monolayer study. AB - Classical lipases are well known for being enzymes hydrolysing triacylglycerols as substrate, except the porcine pancreatic lipase (PPL) which was able to hydrolyze phosphatidylcholine. Amino acid sequence alignments revealed that Valine 260 residue in PPL lid, postulated to be responsible for the PPL phospholipase activity, was present in the Turkey pancreatic lipase (TPL). The importance of Val 260 in the phospholipase activities expression has been reported. To confirm this fact, Val 260 was mutated to Alanine in the TPL lid. Mutated protein has conserved its phospholipase activity as well as the non mutated TPL. Therefore, Valine 260 residue in the lid is not involved in the pancreatic lipases phospholipase activity. The rTPL phospholipase activity was also studied using monolayer technique. This avian pancreatic lipase has shown phospholipase activity toward differently charged phospholipids. The highest phospholipase activity was found on phosphatidylglycerol (negatively charged substrate) at a surface pressure of 20mN/m, but when a zwitterionic substrate was used (DLPC), a lower activity was found at a surface pressure of 10mN/m. However, it is worth noticing that the TPL phospholipase activity is about 100 fold lower than its lipase activity. GC chromatography analyses of the released fatty acids from the hydrolysis of 1,2-POPC have shown that rTPL hydrolyses esters bonds at the sn-1 as well as the sn-2 position of phospholipids. Hence, rTPL shows a low phospholipase activity in comparison to its activity toward triacylglycerols. PMID- 26277751 TI - Role of the salt bridge between glutamate 546 and arginine 907 in preservation of autoinhibited form of Apaf-1. AB - Apaf-1, the key element of apoptotic mitochondrial pathway, normally exists in an auto-inhibited form inside the cytosol. WRD-domain of Apaf-1 has a critical role in the preservation of auto-inhibited form; however the underlying mechanism is unclear. It seems the salt bridges between WRD and NOD domains are involved in maintaining the inactive conformation of Apaf-1. At the present study, we have investigated the effect of E546-R907 salt bridge on the maintenance of auto inhibited form of human Apaf-1. E546 is mutated to glutamine (Q) and arginine (R). Over-expression of wild type Apaf-1 and its E546Q and E546R variants in HEK293T cells does not induce apoptosis unlike - HL-60 cancer cell line. In vitro apoptosome formation assay showed that all variants are cytochrome c and dATP dependent to form apoptosome and activate endogenous procaspase-9 in Apaf-1 knockout MEF cell line. These results suggest that E546 is not a critical residue for preservation of auto-inhibited Apaf-1. Furthermore, the behavior of Apaf-1 variants for in vitro apoptosome formation in HEK293T cell is similar to exogenous wild type Apaf-1. Wild type and its variants can form apoptosome in HEK293T cell with different procaspase-3 processing pattern in the presence and absence of exogenous cytochrome c and dATP. PMID- 26277752 TI - Alyssum homolocarpum seed gum: Dilute solution and some physicochemical properties. AB - The objective of this study was to investigate the effect of various temperatures (25-65 degrees C) on some dilute solution properties of Alyssum homolocarpum seed gum (AHSG) as a novel potential source of hydrocolloid. Monosaccharide composition, FTIR analysis and molecular parameters were determined to provide more structural information. The results indicated that AHSG had a low molecular weight (3.66*10(5)Da), medium intrinsic viscosity (18.34dl/g) at 25 degrees C, relatively flexible chain with a chain flexibility parameter of 618.54, and activation energy of 0.51*10(7)J/kgmol. With rise in temperature from 25 to 55 degrees C, the intrinsic viscosity decreased as well as coil radius and volume of AHSG. The shape factor of AHSG macromolecule was spherical at all temperatures. The electrostatic interaction and particle size of AHSG solution were -25.81mV (at neutral pH) and 225.36nm, respectively. The results revealed that AHSG had high total sugar content (85.33%), small amount of uronic acids (5.63%) and it is likely a galactan-type polysaccharide. The FTIR spectra showed that AHSG behaved like a typical polyelectrolyte because of the presence of carboxyl and hydroxyl groups. PMID- 26277753 TI - A balanced JA/ABA status may correlate with adaptation to osmotic stress in Vitis cells. AB - Water-related stress is considered a major type of plant stress. Osmotic stress, in particular, represents the common part of all water-related stresses. Therefore, plants have evolved different adaptive mechanisms to cope with osmotic related disturbances. In the current work, two grapevine cell lines that differ in their osmotic adaptability, Vitis rupestris and Vitis riparia, were investigated under mannitol-induced osmotic stress. To dissect signals that lead to adaptability from those related to sensitivity, osmotic-triggered responses with respect to jasmonic acid (JA) and its active form JA-Ile, abscisic acid (ABA), and stilbene compounds, as well as the expression of their related genes were observed. In addition, the transcript levels of the cellular homeostasis gene NHX1 were examined. The data are discussed with a hypothesis suggesting that a balance of JA and ABA status might correlate with cellular responses, either guiding cells to sensitivity or to progress toward adaptation. PMID- 26277754 TI - Comparison of individual and combined effects of salinity and deficit irrigation on physiological, nutritional and ornamental aspects of tolerance in Callistemon laevis plants. AB - The effect of water deficit, salinity and both applied simultaneously on several physiological and morphological parameters in the ornamental plant Callistemon laevis was studied to identify the tolerance mechanisms developed by this species to these sources of stress and to evaluate their adaptability to such conditions. C. laevis plants were grown in pots outdoors and subjected to four irrigation treatments lasting ten months: control (0.8 dS m(-1), 100% water holding capacity), water deficit (0.8 dS m(-1), 50% of the amount of water supplied in control), saline (4.0 dS m(-1), same amount of water supplied as control) and saline water deficit (4.0 dS m(-1), 50% of the water supplied in the control). Water and saline stress, when applied individually, led to a reduction of 12% and 39% of total biomass, respectively, while overall plant quality (leaf color and flowering) was unaffected. However, saline water deficit affected leaf color and flowering and induced an excessive decrease of growth (68%) due to leaf tissue dehydration and a high leaf Cl and Na concentration. Biomass partitioning depended not only on the amount of water applied, but also on the electrical conductivity of the water. Water stress induced active osmotic adjustment and decreased leaf tissue elasticity. Although both Na and Cl concentrations in the plant tissues increased with salinity, Cl entry through the roots was more restricted. In plants submitted to salinity individually, Na tended to remain in the roots and stems, and little reached the leaves. However, plants simultaneously submitted to water and saline stress were not able to retain this ion in the woody parts. The decrease in stomatal conductance and photosynthesis was more marked in the plants submitted to both stresses, the effect of which decreased photosynthesis, and this together with membrane damage delayed plant recovery. The results show that the combination of deficit irrigation and salinity in C. laevis is not recommended since it magnifies the adverse effects of either when applied individually. PMID- 26277755 TI - Five new compounds from the fungus Ganoderma petchii. AB - The fungal species of the genus Ganoderma attracted great interest in the last decades. Our recent investigation on Ganoderma petchii afforded five new compounds, (-)-petchioics A and B (1 and 2), petchiates A and B (3 and 4), petchine (5), and a known compound. The structures of the new compounds were elucidated on the basis of spectroscopic data. The absolute configurations of 1 and 2 were assigned by computational methods. Biological activities of these isolates towards human cancer cells, COX-1/2, and influenza virus were evaluated. PMID- 26277756 TI - Does Streptococcus mitis, a neonatal oropharyngeal bacterium, influence the pathogenicity of Pseudomonas aeruginosa? AB - Microorganisms in a biofilm might promote or suppress each other. We previously found that Pseudomonas aeruginosa (P. aeruginosa) and the normal colonized bacteria in the oropharynx, Streptococcus mitis (S. mitis), were the most common bacteria in the biofilm found on newborns' endotracheal tubes. Here, we found that S. mitis enhanced the adhesion and biofilm formation of P. aeruginosa. Furthermore, it alleviated the immune response induced by P. aeruginosa. These findings remind us that we should not ignore the role of traditionally viewed non pathogenic bacteria in biofilms and provide new insights into exploring bacterial interaction mechanisms in biofilm related infections. PMID- 26277757 TI - Synthesis, biological evaluation and docking study of maleimide derivatives bearing benzenesulfonamide as selective COX-2 inhibitors and anti-inflammatory agents. AB - A series of maleimide analogs bearing benzenesulfonamide were synthesized (4a-r). The anti-inflammatory activity of synthesized derivatives was evaluated using carrageenan induced rat paw edema model. COX-1 and COX-2 potency was evaluated through in vitro cyclooxygenase assays. The results revealed that, compounds 4a, 4h, 4 j, 4 k and 4r had potent COX-2 percentage inhibition as well as in vivo anti-inflammatory activity. The potent compound 4 j was docked into the COX-2 active site to determine the probable binding model. The results of in vivo and in vitro studies demonstrate that phenyl ring with electron withdrawing groups on maleimide ring would generate more potent anti-inflammatory agents. Thus, these compounds can serve as potential leads for further anti-inflammatory studies. PMID- 26277758 TI - Discovery of N-(4-aryl-5-aryloxy-thiazol-2-yl)-amides as potent RORgammat inverse agonists. AB - A novel series of N-(4-aryl-5-aryloxy-thiazol-2-yl)-amides as RORgammat inverse agonists was discovered. Binding mode analysis of a RORgammat partial agonist (2c) revealed by co-crystal structure in RORgammat LBD suggests that the inverse agonists do not directly interfere with the interaction between H12 and the RORgammat LBD. Detailed SAR exploration led to identification of potent RORgammat inverse agonists such as 3m with a pIC50 of 8.0. Selected compounds in the series showed reasonable activity in Th17 cell differentiation assay as well as low intrinsic clearance in mouse liver microsomes. PMID- 26277759 TI - Discovery of thieno[3,2-c]pyridin-4-amines as novel Bruton's tyrosine kinase (BTK) inhibitors. AB - A novel series of BTK inhibitors bearing thieno[3,2-c]pyridin-4-amine framework as the core scaffold were designed, synthesized and well characterized. In this paper, twenty one compounds displayed variant inhibitory activities against BTK in vitro, and compound 14 g showed the most potent inhibitory activity against BTK enzyme, with the IC50 value of 12.8 nM. Moreover, compounds 14 g displayed relatively good kinase selectivity and was subsequently evaluated in vivo for profiling its PK properties. This work identified the thieno[3,2-c]pyridin-4 amine derivatives as novel BTK inhibitors and verified the value of thieno[3,2 c]pyridin-4-amine scaffold in drug design. PMID- 26277760 TI - Design, chemical synthesis and biological evaluation of 3-spiromorpholinone/3 spirocarbamate androsterone derivatives as inhibitors of 17beta-hydroxysteroid dehydrogenase type 3. AB - 17beta-Hydroxysteroid dehydrogenase type 3 (17beta-HSD3) is a key enzyme involved in the biosynthesis of testosterone and dihydrotestosterone. These hormones are known to stimulate androgen-dependent prostate cancer. In order to generate effective inhibitors of androgen biosynthesis without androgenic effect, we synthesized a new family of 3-spiromorpholinone and 3-spirocarbamate androsterone derivatives bearing diversified hydrophobic groups. We also tested their inhibitory activity in a microsomal fraction of 17beta-HSD3-containing rat testes, and their androgenic effect on androgen-sensitive LAPC-4 cells. From our first structure-activity relationship (SAR) study, we noted that compound 7e inhibited 17beta-HSD3 (77% at 0.1 MUM) compared to our reference compound RM-532 105 (76% at 0.1 MUM), but exhibited a residual androgenic effect. A library of 7e analogue compounds was next synthesized in order to generate compounds with reduced androgenic activity. In this new SAR study, the sulfonamide compound 7e21 and the carboxamide compound 7e22 inhibited 17beta-HSD3 (IC50 = 28 and 88 nM, respectively). These two compounds were not androgenic and not cytotoxic even at the highest concentration tested, but their inhibitory activity decreased in intact LNCaP cells overexpressing 17beta-HSD3 (LNCaP[17beta-HSD3]). Structural modifications of these two lead compounds could however be tested to produce a second generation of 17beta-HSD3 inhibitors. PMID- 26277761 TI - Multiple metastases to vertebrae after surgical management, chemotherapy, and bone marrow transplantation for granulocytic sarcoma of the spine. PMID- 26277762 TI - Severe thoracic kyphosis. PMID- 26277763 TI - Changing the Carburetor Without Changing the Plugs: The Intersection of Stock Car Racing With Mechanically Assisted Circulation. PMID- 26277764 TI - Long-Term Extrapolation of Clinical Benefits Among Patients With Mild Heart Failure Receiving Cardiac Resynchronization Therapy: Analysis of the 5-Year Follow-Up From the REVERSE Study. AB - OBJECTIVES: This study sought to assess the lifelong extrapolated patient outcomes with cardiac resynchronization therapy (CRT) in mild heart failure (HF), beyond the follow-up of randomized clinical trials (RCTs). BACKGROUND: RCTs have demonstrated short-term survival and HF hospitalization benefits of CRT in mild HF. We used data from the 5-year follow-up of the REVERSE (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction) study to extrapolate survival and HF hospitalizations. We compared CRT-ON versus CRT-OFF and CRT defibrillators (CRT-D) versus CRT pacemakers (CRT-P). METHODS: Multivariate regression models were used to estimate treatment-specific all-cause mortality, disease progression, and HF-related hospitalization rates. Rank preserving structural failure time (RPSFT) models were used to adjust for protocol-mandated crossover in the survival analysis. RESULTS: CRT-ON was predicted to increase survival by 22.8% (CRT-ON 52.5% vs. CRT-OFF 29.7%; hazard ratio [HR]: 0.45; p = 0.21), leading to an expected survival of 9.76 years (CRT ON) versus 7.5 years (CRT-OFF). CRT-D showed a significant improvement in survival compared with CRT-P (HR: 0.47; 95% confidence interval [CI]: 0.25 to 0.88; p = 0.02) and were predicted to offer 2.77 additional life-years. New York Heart Association (NYHA) functional class II patients had a 30.6% higher HF hospitalization risk than class I (I vs. II incident rate ratio [IRR]: 0.69; 95% CI: 0.57 to 0.85; p < 0.001) and 3 times lower rate compared with class III (III vs. II IRR: 2.98; 95% CI: 2.29 to 3.87; p < 0.001). CONCLUSIONS: RPSFT estimates yielded results demonstrating clinically important long-term benefit of CRT in mild HF. CRT was predicted to reduce mortality, with CRT-D prolonging life more than CRT-P. NYHA functional class I/II patients were shown to have a significantly reduced risk of HF hospitalization compared with class III, leading to CRT reducing HF hospitalization rates. PMID- 26277765 TI - Physical Activity and Heart Failure Risk in a Prospective Study of Men. AB - OBJECTIVES: This study investigated if total physical activity, as well as different types of physical activity, were associated with heart failure risk. BACKGROUND: Physical activity has shown to be associated with reduced risks of coronary heart disease and stroke. Studies have also suggested that physical activity is associated with heart failure development. METHODS: A study population of 33,012 men was followed from beginning of 1998 until the end of 2012. First event of heart failure was ascertained through linkage to the Swedish National Patient Register and Cause of Death Register. The data were analyzed by using Cox proportional hazards regression and Laplace regression. RESULTS: During a mean follow-up of 13 years, we ascertained a total of 3,609 first events of heart failure. The average age at study baseline was 60 +/- 9 years of age. When examining the entire study population, a U-shaped association between total physical activity and heart failure risk was detected, with both extremely high (57 metabolic equivalent [MET] h/day) and extremely low (38 MET h/day) levels of total physical activity associated with an increased risk of heart failure. When investigating different types of physical activity, we found that walking/bicycling at least 20 min/day was associated with 21% lower risk of heart failure (95% confidence interval: 0.72 to 0.87); corresponding to a median age at heart failure 8 months later for those who had actively walked or biked daily. When looking at long-term behavior of walking/bicycling, the results suggested a trend toward more recent active behavior being more related to heart failure protection than past physical activity levels. CONCLUSIONS: This study suggests that both low levels and high levels of total physical activity, in comparison with moderate levels, could increase heart failure risk in men and that certain types of physical activity are associated with a protective effect on heart failure in men. When examining different types of physical activity, walking/bicycling at least 20 min per day was associated with the largest risk reduction of heart failure. PMID- 26277766 TI - Cardiac Resynchronization Therapy for Mild Heart Failure: Compelling Evidence of Long-Term Benefits. PMID- 26277767 TI - Green Means Go ... Physical Activity and the Prevention of Heart Failure. PMID- 26277769 TI - Functional characterization of a plastidal cation-dependent O-methyltransferase from the liverwort Plagiochasma appendiculatum. AB - Caffeoyl CoA O-methyltransferases (CCoAOMTs), known to be involved in phenylpropanoid metabolism and lignin synthesis, have been characterized from several higher plant species, which also harbor CCoAOMT-like enzymes responsible for methylation of a variety of flavonoids, anthocyanins, coumarins and phenylpropanoids. Here, a gene encoding a CCoAOMT (PaOMT1) was isolated from a sequenced cDNA library of the liverwort species Plagiochasma appendiculatum, a species belonging to the Family Aytoniaceae. The full-length cDNA sequence of PaOMT1 contains 909 bp, and is predicted to encode a protein with 302 amino acids. The gene products were 40-50% identical to CCoAOMT sequences of other plants. Experiments based on recombinant PaOMT1 showed that the enzyme was able to methylate phenylpropanoids, flavonoids and coumarins, with a preference for the flavonoid quercetin (19). Although the substrate selectivity and biochemical feature of PaOMT1 is similar to CCoAOMT-like enzymes, the sequence alignment results indicated PaOMT1 is closer to true CCoAOMT enzymes. A phylogenetic analysis indicated that PaOMT1 is intermediate between true CCoAOMTs and CCoAOMT like enzymes. The transient expression of a PaOMT1-GFP fusion in tobacco demonstrated that PaOMT1 is directed to the plastids. PaOMT1 may represent an ancestral form of higher plant true CCoAOMT and CCoAOMT-like enzymes. This is the first time an O-methyltransferase was characterized in liverworts. PMID- 26277768 TI - Further Peripheral Vascular Dysfunction in Heart Failure Patients With a Continuous-Flow Left Ventricular Assist Device: The Role of Pulsatility. AB - OBJECTIVES: Using flow-mediated vasodilation (FMD) and reactive hyperemia (RH), this study aimed to provide greater insight into left ventricular assist device (LVAD)-induced changes in peripheral vascular function. BACKGROUND: Peripheral endothelial function is recognized to be impaired in patients with heart failure with reduced ejection fraction (HFrEF), but the peripheral vascular effects of continuous-flow LVAD implantation, now used as either a bridge to transplantation or as a destination therapy, remain unclear. METHODS: Sixty-eight subjects (13 New York Heart Association [NYHA] functional class II HFrEF patients, 19 NYHA functional class III/IV HFrEF patients, 20 NYHA functional class III/IV HFrEF patients post-LVAD implantation, and 16 healthy age-matched control subjects) underwent FMD and RH testing in the brachial artery with blood flow velocity, artery diameters, and pulsatility index (PI) assessed by ultrasound Doppler. RESULTS: PI was significantly lower in the LVAD group (2.0 +/- 0.4) compared with both the HFrEF II (8.6 +/- 0.8) and HFrEF III/IV (8.1 +/- 0.9) patients, who, in turn, had significantly lower PI than the control subjects (12.8 +/- 0.9). Likewise, LVAD %FMD/shear rate (0.09 +/- 0.01 %Delta/s(-1)) was significantly reduced compared with all other groups (control subjects, 0.24 +/- 0.03; HFrEF II, 0.17 +/- 0.02; and HFrEF III/IV, 0.13 +/- 0.02 %Delta/s(-1)), and %FMD/shear rate significantly correlated with PI (r = 0.45). RH was unremarkable across groups. CONCLUSIONS: Although central hemodynamics are improved in patients with HFrEF by a continuous-flow LVAD, peripheral vascular function is further compromised, which is likely due, at least in part, to the reduction in pulsatility that is a characteristic of such a mechanical assist device. PMID- 26277770 TI - Oxylipins in the spikemoss Selaginella martensii: Detection of divinyl ethers, 12 oxophytodienoic acid and related cyclopentenones. AB - Green tissues of spikemoss Selaginella martensii Spring possessed the complex oxylipins patterns. Major oxylipins were the products of linoleic and alpha linolenic acids metabolism via the sequential action of 13-lipoxygenase and divinyl ether synthase (DES) or allene oxide synthase (AOS). AOS products were represented by 12-oxophytodienoic acid (12-oxo-PDA) isomers. Exceptionally, S. martensii possesses high level of 12-oxo-9(13),15-PDA, which is very uncommon in flowering plants. Separate divinyl ethers were purified after micro-preparative incubations of linoleic or alpha-linolenic acids with homogenate of S. martensii aerial parts. The NMR data allowed us to identify all geometric isomers of divinyl ethers. Linoleic acid was converted to divinyl ethers etheroleic acid, (11Z)-etheroleic acid and a minority of (omega5Z)-etheroleic acid. With alpha linolenate precursor, the specificity of divinyl ether biosynthesis was distinct. Etherolenic and (omega5Z)-etherolenic acids were the prevailing products while (11Z)-etherolenic acid was a minor one. Divinyl ethers are detected first time in non-flowering land plant. These are the first observations of fatty acid metabolism through the lipoxygenase pathway in spikemosses (Lycopodiophyta). PMID- 26277771 TI - Suicide in Portugal: Spatial determinants in a context of economic crisis. AB - This study compares the existing statistical association between suicide mortality and the characteristics of places of residence (municipalities), before and during the current economic crisis, in Portugal. We found that (1) the traditional culture-based North/South pattern of suicidal behaviour has faded away, while the socioeconomic urban/rural divide has become more pronounced; (2) suicide is associated with higher levels of rurality and material deprivation; and (3) recent shifts in suicidal trends may result from the current period of crisis. Strategies targeting rural areas combined with public policies that address area deprivation may have important implications for tackling suicide. PMID- 26277772 TI - Journeying with HIV patients across the health care spectrum - an examination of a seamless model of HIV Psychiatry of a large urban general hospital. AB - OBJECTIVE: To describe a model of HIV psychiatry used in an urban hospital in Toronto and examine it against current literature. METHOD: Using a narrative method, we elaborate on how this model delivers care across many different settings and the integral roles that the HIV psychiatrist plays in each of these settings. This is articulated against a backdrop of existing literature regarding models of HIV care. RESULTS: This model is an example of an integrated model as opposed to a traditional consultation-liaison model and is able to deliver seamless care while remaining focused on patient-centric care. CONCLUSION: An HIV psychiatrist delivers seamless and patient-centric care by journeying with patients across the healthcare spectrum and playing different roles in different care settings. PMID- 26277774 TI - Single-dose serotonergic stimulation shows widespread effects on functional brain connectivity. AB - The serotonergic system is widely distributed throughout the central nervous system. It is well known as a mood regulating system, although it also contributes to many other functions. With resting state functional magnetic resonance imaging (RS-fMRI) it is possible to investigate whole brain functional connectivity. We used this non-invasive neuroimaging technique to measure acute pharmacological effects of the selective serotonin reuptake inhibitor sertraline (75 mg) in 12 healthy volunteers. In this randomized, double blind, placebo controlled, crossover study, RS-fMRI scans were repeatedly acquired during both visits (at baseline and 3, 5, 7 and 9h after administering sertraline or placebo). Within-group comparisons of voxelwise functional connectivity with ten functional networks were examined (p<0.005, corrected) using a mixed effects model with cerebrospinal fluid, white matter, motion parameters, heart rate and respiration as covariates. Sertraline induced widespread effects on functional connectivity with multiple networks; the default mode network, the executive control network, visual networks, the sensorimotor network and the auditory network. A common factor among these networks was the involvement of the precuneus and posterior cingulate cortex. Cognitive and subjective measures were taken as well, but yielded no significant treatment effects, emphasizing the sensitivity of RS-fMRI to pharmacological challenges. The results are consistent with the existence of an extensive serotonergic system relating to multiple brain functions with a possible key role for the precuneus and cingulate. PMID- 26277773 TI - Rapid multi-orientation quantitative susceptibility mapping. AB - Three-dimensional gradient echo (GRE) is the main workhorse sequence used for susceptibility weighted imaging (SWI), quantitative susceptibility mapping (QSM), and susceptibility tensor imaging (STI). Achieving optimal phase signal-to-noise ratio requires late echo times, thus necessitating a long repetition time (TR). Combined with the large encoding burden of whole-brain coverage with high resolution, this leads to increased scan time. Further, the dipole kernel relating the tissue phase to the underlying susceptibility distribution undersamples the frequency content of the susceptibility map. Scans at multiple head orientations along with calculation of susceptibility through multi orientation sampling (COSMOS) are one way to effectively mitigate this issue. Additionally, STI requires a minimum of 6 head orientations to solve for the independent tensor elements in each voxel. The requirements of high-resolution imaging with long TR at multiple orientations substantially lengthen the acquisition of COSMOS and STI. The goal of this work is to dramatically speed up susceptibility mapping at multiple head orientations. We demonstrate highly efficient acquisition using 3D-GRE with Wave-CAIPI and dramatically reduce the acquisition time of these protocols. Using R=15-fold acceleration with Wave-CAIPI permits acquisition per head orientation in 90s at 1.1mm isotropic resolution, and 5:35min at 0.5mm isotropic resolution. Since Wave-CAIPI fully harnesses the 3D spatial encoding capability of receive arrays, the maximum g-factor noise amplification remains below 1.30 at 3T and 1.12 at 7T. This allows a 30-min exam for STI with 12 orientations, thus paving the way to its clinical application. PMID- 26277775 TI - Area-level socioeconomic context, total mortality and cause-specific mortality in Spain: Heterogeneous findings depending on the level of geographic aggregation. AB - The objective of this study was to estimate the association between area-level socioeconomic context and mortality in Spain, using two different geographic aggregations. Nation-wide prospective study covering all persons living in Spain in 2001. Mortality was analysed in Spanish citizens by province of residence and in citizens of Madrid by neighbourhood of residence. Provinces and neighbourhoods were grouped into quartiles according to two socioeconomic indicators: percentage of the population with university education and unemployment rate. The measure of association was the rate ratio for total mortality and cause-specific mortality, by each socioeconomic indicator in two age groups, 25-64 years (adult population) and 65 years and over (elderly population). After adjustment for all individual socioeconomic variables, the rate ratio for total mortality among residents in the provinces with the worst versus best socioeconomic context was 0.92 (95% CI 0.88-0.97) when the indicator was percentage of university population and 0.89 (0.85-0.93) when it was unemployment rate in the adult population, and 1.05 (1.00 1.11) and 1.08 (1.03-1.13), respectively, in the elderly population. No significant differences in mortality were observed between adults residing in neighbourhoods with the worst versus best socioeconomic context, but in the elderly population the mortality rate ratios for the two socioeconomic indicators were 1.04 (1.01-1.07) and 1.06 (1.03-1.09), respectively. Residents in provinces with the worst socioeconomic context had the lowest mortality from cancer and external causes and the highest mortality from cardiovascular diseases, while residents in neighbourhoods with the worst socioeconomic context had the highest mortality from respiratory and digestive diseases. Further research should find out the reasons for the lower total mortality in adult population residing in the Spanish provinces with the most adverse socioeconomic context and the reasons for excess mortality from digestive diseases and respiratory diseases among residents in neighbourhoods with the worst socioeconomic context. PMID- 26277776 TI - A RepA-like protein from bacteriophage BFK20 is a multifunctional protein with primase, polymerase, NTPase and helicase activities. AB - Phage BFK20 replication protein gp43 comprises an N-terminal prim-pol domain and a C-terminal domain similar to replicative helicases. We prepared and studied two recombinant proteins: gp43-1 containing both prim-pol and helicase domains, and gp43C with the helicase domain only. A SEC-MALS analysis indicated that gp43-1 forms a hexameric homooligomer. NTPase activity testing revealed that gp43-1 was able to hydrolyze a wide spectrum of NTPs, ATP the most efficiently. The ATPase activity of gp43-1 was strongly dependent on the presence of ssDNA in the reaction, but was low in the presence of dsDNA and in the absence of DNA. On the other hand, the ATPase activity of gp43C was very low regardless of the presence of DNA. The helicase activity of gp43-1 was detected using a fluorescence-based assay with a forked DNA substrate in the presence of ATP. However, no helicase activity could be detected for gp43C. We therefore conclude that the prim-pol domain is essential for the helicase and ssDNA-dependent ATPase activity of gp43 1. PMID- 26277777 TI - Identification of CCL2, RARRES2 and EFNB2 as host cell factors that influence the multistep replication of respiratory syncytial virus. AB - Human respiratory syncytial virus (RSV) is a major causative agent of respiratory tract infections in children worldwide. Preterm children or those with underlying cardiopulmonary disorders are at particularly high risk of developing severe and lethal RSV respiratory tract infections; however, there are currently no effective vaccines or anti-viral drugs. To identify targets for the development of drugs to treat RSV infections, we investigated host cell factors involved in the replication of RSV. To this end, MDCK cells with low susceptibility to RSV were transfected with cDNA libraries derived from RSV-susceptible human lung or HeLa cells. A microarray analysis was subsequently performed on parental MDCK cells and MDCK cells that were converted to an RSV-susceptible form. Among the genes identified, chemokine (C-C motif) ligand 2 (CCL2), retinoic acid receptor responder protein 2 (RARRES2) and ephrin-B2 (EFNB2) had a positive effect on RSV replication. Expression of these genes in MDCK cells resulted in a 10- to 100 fold increase in RSV replication. CCL2 expression also disrupted the distribution of claudin-1, a tight junction protein, suggesting that CCL2 plays a role in claudin-based tight junction formation during RSV replication. The knockdown of EFNB2 and RARRES2 by siRNA in RSV-susceptible cell lines (HEp-2 and A549) resulted in reduced RSV replication, suggesting that EFNB2 and RARRES2 participate in RSV replication. Together, our findings suggest that CCL2, RARRES2 and EFNB2 are host cell factors involved in RSV replication. PMID- 26277778 TI - Ex vivo modeling of feline herpesvirus replication in ocular and respiratory mucosae, the primary targets of infection. AB - Feline herpesvirus 1 (FeHV-1) is a major cause of rhinotracheitis and ocular diseases in cats. In the present study, the viral replication at the primary infection sites was studied using feline respiratory and ocular mucosa explants. The explants of three cats were maintained in an air-liquid culture up to 96 hours without loss of viability. After inoculation with FeHV-1 (C27), no evidence of infection was noted in corneal epithelium, while plaque-wise replication was observed in conjunctival and tracheal mucosae beginning from 24 h post inoculation (hpi). The viral plaque diameters increased over time in trachea and conjunctiva and were larger in tracheal explants than in conjunctival explants at 48 hpi. FeHV-1 penetrated the basement membrane in conjunctival and tracheal explants between 24 and 48 hpi. At 48 and 72 hpi, viral invasion was going deeper in tracheal explants than in conjunctival explants. Our study indicates that FeHV 1 has a better capacity to invade the respiratory mucosa than the conjunctival mucosa, and prefers the conjunctiva, but not the cornea as a portal of entry during ocular infection. PMID- 26277779 TI - [Managing acute supraventricular arrhythmia in pregnancy]. AB - Palpitations: frequent reason for referral to a cardiologist. Arrythmia: rare, mostly benign. Premature extra-beats and sustained tachy-arrhythmias: more frequent or revealed during pregnancy. Hemodynamic changes in expectant women favor an environment conducive to arrhythmogenesis. AF and flutter: very rare unless structural heart disease or hyperthyroidism. Drugs: careful monitoring of the patient and dose adjustments. Cardioversion: only in case of severe symptoms or hemodynamically unstable. PMID- 26277780 TI - [Translational pharmacology: Rationality or serendipity? Letter on the article "Endothelin: From discovery to pharmacotherapeutic innovations"]. PMID- 26277781 TI - Does maternal race influence the short-term variation of the fetal heart rate? An historical cohort study. AB - OBJECTIVES: The main aim of this article was to analyze short-term variation (STV) of the fetal heart rate according to maternal race. The secondary aim was to study the baseline fetal heart rate according to this factor. STUDY DESIGN: This single-center historical cohort study covered the period from November 2008 through December 2011 (n=182). The inclusion criteria were: black women from sub Saharan Africa or white European women, with a singleton pregnancy >=34 weeks and fetal heart rate recorded by computerized analysis (Oxford Sonicaid System 8002) at a prenatal visit. The exclusion criteria were: medication likely to modify fetal heart rate, abnormal fetal heart rate tracing, and being in labor. A multiple linear regression analysis was used to study the association between maternal race and STV. RESULTS: STV was lower by 2.6ms in fetuses of black women (n=55) compared to those of white women (n=127) (8.9+/-2.1ms vs. 11.4+/-3.4ms) (p<0.001). The basal fetal heart rate was higher (p=0.001), and the recording criteria were met less often for the black women (p=0.04). After adjustment for maternal age, body mass index at the beginning of pregnancy, maternal cigarette smoking, parity, gestational diabetes, gestational age at the time of the fetal heart rate recording, and the time between the last meal and the recording, mean STV was lower by 3.1+/-0.6ms in fetuses of black compared with white women (p<0.001). CONCLUSION: STV is lower in fetuses of black women compared to those of white women in a low-risk population. A study of black and white women with high-risk pregnancies is necessary to assess the impact of medical practices on perinatal outcome after STV analysis. PMID- 26277782 TI - Granulin levels in patients with idiopathic premature ovarian failure. AB - OBJECTIVE: With the prolongation of expected lifespan, premature ovarian failure (POF) has gained increased significance as a crucial female health problem. Here we aimed to investigate the diagnostic value of the levels of the growth factor Granulin, which has been associated with epithelial ovarian carcinoma, in the pathogenesis of POF. STUDY DESIGN: Thirty-one patients with POF and 57 patients as a control group were recruited for this study in a tertiary referral center in the capital of Turkey. Granulin levels and individual characteristics of the two groups were compared. RESULTS: Age and body mass indices were similar between the two groups. Granulin levels in patients with POF (2.94+/-1.91ng/mL) were significantly lower than in the control group (4.77+/-1.62ng/mL) (p<0.001). CONCLUSION: Future larger studies should focus on Granulin levels and its correlation with ovarian reserve markers, its clinical applicability, and its possible therapeutic value, thus providing further insight into the role of Granulin in the pathogenesis of POF. PMID- 26277783 TI - Laparoscopic salvage lateral pelvic lymph node dissection for locally recurrent rectal cancer. AB - AIM: The lateral pelvic lymph nodes are one of the major sites and sources of local recurrence (LR) after surgery for rectal cancer. Salvage lateral pelvic lymph node dissection (LPLD) is potentially curative, but the value of laparoscopic surgery in such cases is unknown. Our aim was to report the technical details of laparoscopic salvage LPLD for LR at these nodes after rectal cancer surgery. METHOD: The study was based on nine patients who underwent laparoscopic salvage LPLD for LR at the lateral pelvic lymph nodes after surgery for rectal cancer. The safety and feasibility of this procedure were determined. RESULTS: The median operation time was 381 min and the median estimated blood loss was 130 ml. There were no conversions. Adjacent structures removed en bloc were the pelvic plexus in four patients, the internal iliac artery in seven patients and the seminal vesicle in one patient. The median number of metastatic lymph nodes was 1 (range 1-11). CONCLUSION: Our novel technique of laparoscopic salvage LPLD for LR at the lateral pelvic lymph nodes is safe and feasible. PMID- 26277784 TI - Exploring teams of learners becoming "WE" in the Intensive Care Unit--a focused ethnographic study. AB - BACKGROUND: Research about collaboration within teams of learners in intensive care is sparse, as is research on how the learners in a group develop into a team. The aim of this study was to explore the collaboration in teams of learners during a rotation in an interprofessional education unit in intensive care from a sociocultural learning perspective. METHODS: Focused Ethnographic methods were used to collect data following eight teams of learners in 2009 and 2010. Each team consisted of one resident, one specialist nurse student and their supervisors (n = 28). The material consisted of 100 hours of observations, interviews, and four hours of sound recordings. A qualitative analysis explored changing patterns of interplay through a constant comparative approach. RESULTS: The learners' collaboration progressed along a pattern of participation common to all eight groups with a chronological starting point and an end point. The progress consisted of three main steps where the learners' groups developed into teams during a week's training. The supervisors' guided the progress by gradually stepping back to provide latitude for critical reflection and action. CONCLUSION: Our main conclusion in training teams of learners how to collaborate in the intensive care is the crucial understanding of how to guide them to act like a team, feel like a team and having the authority to act as a team. PMID- 26277785 TI - Microvascular resistance in response to iodinated contrast media in normal and functionally impaired kidneys. AB - Contrast-induced nephropathy (CIN) is considered to result from intrarenal vasoconstriction, and occurs more frequently in impaired than in normal kidneys. It was hypothesized that iodinated contrast media would markedly change renal blood flow and vascular resistance in functionally impaired kidneys. Thirty-six patients were enrolled (32 men; mean age, 75.3 +/- 7.6 years) undergoing diagnostic coronary angiography and were divided into two groups based on the presence of chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min per 1.73 m(2) (CKD and non-CKD groups, n = 18 in both). Average peak velocity (APV) and renal artery resistance index (RI) were measured by Doppler flow wire before and after administration of the iodinated contrast media. The APV and the RI were positively and inversely correlated with the eGFR at baseline, respectively (APV, R = 0.545, P = 0.001; RI, R = -0.627, P < 0.001). Mean RI was significantly higher (P = 0.015) and APV was significantly lower (P = 0.026) in the CKD than in the non-CKD group. Both APV (P < 0.001) and RI (P = 0.002) were significantly changed following contrast media administration in the non-CKD group, but not in the CKD group (APV, P = 0.258; RI, P = 0.707). Although renal arterial resistance was higher in patients with CKD, it was not affected by contrast media administration, suggesting that patients with CKD could have an attenuated response to contrast media. PMID- 26277786 TI - Expression profiling of angiogenesis-related genes in brain metastases of lung cancer and melanoma. AB - Brain metastases (BM) are the most common brain tumors of adults and are associated with fatal prognosis. Formation of new blood vessels, named angiogenesis, was proposed to be the main hallmark of the growth of BM. Previous preclinical evidence revealed that angiogenic blockage might be considered for treatment; however, there were varying responses. In this study, we aimed to characterize the expression pattern of angiogenesis-related genes in BM of lung cancer and melanoma, which might be of importance for the different responses against anti-angiogenic treatment. Fifteen snap-frozen tissues obtained from BM of non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), and melanoma patients were analyzed for angiogenesis-related genes using a commercially available gene expression kit. Epilepsy tissue was used as control. Expression values were analyzed using hierarchical clustering investigating relative fold changes and mapping to Omicsnet protein interaction network. CXCL10, CEACAM1, PECAM1, KIT, COL4A2, COL1A1, and HSPG2 genes were more than 50 fold up-regulated in all diagnosis groups when compared to control, whereas genes such as ANGPT4, PDGFRB, and SERPINF1 were down-regulated only in SCLC and melanoma groups, respectively. Using hierarchical clustering, 12 out of 15 cases were allocated to the correct histological primary tumor type. We identified genes with consistent up-regulation in BM of lung cancer and melanoma and other genes with differential expression across BM of these tumor types. Our data may be of relevance for targeted therapy or prophylaxis of BM using anti-angiogenic agents. PMID- 26277787 TI - miR-211 promotes non-small cell lung cancer proliferation by targeting SRCIN1. AB - MicroRNAs (miRNAs) are a class of small non-coding RNAs that, when dysregulated, are involved in the initiation and progression of various cancers, including lung cancer, in humans. In the current study, qRT-PCR was performed to measure miR-211 expression in human non-small cell lung cancer (NSCLC) cell lines and tissues. Cell proliferation, cell cycle, colony formation, and invasion were performed to detect the functional role of miR-211 in human NSCLC cell line. We used luciferase reporter assay to find the potential target of miR-211. We found that miR-211 expression was upregulated in human non-small cell lung cancer (NSCLC) cell lines and tissues. The overexpression of miR-211 enhanced NSCLC cell proliferation, colony formation, and invasion. SRC kinase signaling inhibitor 1 (SRCIN1) was identified as a direct target of miR-211. SRCIN1 silencing promoted cell proliferation, and SRCIN1 expression was downregulated in human NSCLC cell lines. Thus, miR-211 may function as an oncogenic miRNA in NSCLC, partly by regulating SRCIN1, and the modulation of miR-211 expression represents a potential strategy for the treatment of NSCLC patients. PMID- 26277789 TI - RETRACTED ARTICLE: Downregulation of miR-133b/miR-503 acts as efficient prognostic and diagnostic factors in patients with osteosarcoma and these predictor biomarkers are correlated with overall survival. PMID- 26277788 TI - Targeting polyamine biosynthetic pathway through RNAi causes the abrogation of MCF 7 breast cancer cell line. AB - The diamine putrescine and polyamines, spermidine (triamine) and spermine (tetraamine) are small organic polycations that play an indispensable role in key cellular processes such as the regulation of growth, differentiation, and macromolecular functions. Elevated levels of polyamines (PAs) have been shown to be one of the major factors involved in carcinogenesis. In this study, specific silencing of the expression of three genes of PA biosynthesis pathway, ornithine decarboxylase (ODC), S-adenosylmethionine decarboxylase (SAMDC), and spermidine synthase (SPDSYN) was achieved using RNA interference in MCF 7 breast cancer cell line. For optimizing the effective small interfering nucleic acid (siNA), three variants of ODC siNA [siRNA, locked nucleic acid (LNA)-modified siRNA, and siHybrid (RNA and DNA hybrid)] were used and a dose- and time-dependent study was conducted. The PA biosynthetic genes were targeted individually and in combination. RNAi-mediated reduction in the expression of PA biosynthesis genes resulted in distorted cell morphology, reduced cancer cell viability, and migration characteristic. The most promising results were observed with the combined treatment of siSPDSYN and siODC with 83 % cell growth inhibition. On analyzing the messenger RNA (mRNA) expression profile of the cell cycle and apoptosis-related genes, it was observed that RNAi against PA biosynthetic genes downregulated the expression of CDK8, CCNE2, CCNH, CCNT1, CCNT2, CCNF, PCNA, CCND1, and CDK2, and upregulated the expression of E2F4, BAX, FAS, TP53, CDKN1A, BAK1, CDKN1B, ATM, GRANB, and ATR genes when compared with control-transfected cells. These results suggest that the targeting polyamine biosynthesis through RNAi approach could be a promising strategy for breast cancer therapy and might be extended for therapy of other cancers. PMID- 26277790 TI - Keyhole epilepsy surgery: corticoamygdalohippocampectomy for mesial temporal sclerosis. AB - Surgical approaches for medically refractory mesial temporal lobe epilepsy (MTLE) that previously have been reported include anterior temporal lobectomy (ATL), transcortical selective amygdalohippocampectomy, transsylvian amygdalohippocampectomy, and subtemporal amygdalohippocampectomy. Each approach has its advantages and potential pitfalls. The purpose of this report is to describe our technique of keyhole corticoamygdalohippocampectomy for patients with MTLE due to hippocampal sclerosis. Operations were performed through a 6-cm vertical linear incision and a low 2.5-cm keyhole craniotomy at the anterior squamous temporal bone. Resection of the anterior-most portions of the middle and inferior temporal gyri provided a cylinder-like corridor to the mesial temporal lobe. Identification of the temporal horn through a basal approach was followed by resection of the amygdala, uncus, and hippocampus-parahippocampal gyrus. This 9-year series included 683 patients with a minimum follow-up duration of 2 years. Surgery times were short (range, 1 h 35 min to 2 h 30 min). Only a small percentage of patients had complications (1.76%), and the rate of Engel Class I seizure-free outcome was 87%. No overt speech problems or visual field deficits were identified. Compared with the most popular conventional trans-middle temporal gyrus approach, this technique can make the operation easier, safer, and less traumatic to functional lateral neocortex. PMID- 26277791 TI - Targeted Stage-Specific Inflammatory microRNA Profiling in Urine During Disease Progression in Experimental Autoimmune Encephalomyelitis: Markers of Disease Progression and Drug Response. AB - Recently, microRNAs (miRNAs) have been implicated in regulating neuroinflammatory and demyelinative responses in multiple sclerosis (MS) and its mouse model of experimental autoimmune encephalomyelitis (EAE). miRNAs have also been studied as biomarkers of disease pathology and drug-response in MS. However, no complete miRNA profiling at various stages of EAE disease has been examined, especially in the urine. We carried out a systematic analysis of miRNAs in the urine exosomes as well as in the plasma and spinal cord at pre-onset, onset and peak stages of EAE established in the chronic B6 mice model. For the first time, we provide evidence that urine exosomes can be a specific and sensitive source of miRNA biomarkers for all 3 stages of EAE disease. In a significant observation, we observed that miR-155-5p expression increased in urine exosomes, plasma and spinal cord 6 days before the onset of disease, suggesting its early involvement in the pathology of EAE disease. We also analyzed the effect of Glatiramer acetate (GA; copaxone) treatment, an approved treatment for MS patients, in modulating miRNA expression at the peak of EAE disease. We identified miR-155-5p, miR-27a-3p, miR-9-5p and miR-350-5p as putative GA-treatment responsive miRNA biomarkers. Since, EAE is a mainly CD4 cells mediated disease, we also examined the above set of miRNAs and found to be significantly altered in T cells polarized to Th1 and Th17 phenotype, similar to urine exosomes. Thus, urine exosome miRNAs hold the potential to be defined as novel accessible stage specific biomarkers of EAE (MS) disease as well as treatment response. PMID- 26277792 TI - Bone Imaging and Fracture Risk after Spinal Cord Injury. AB - Spinal cord injury (SCI) is characterized by marked bone loss and an increased risk of fracture with high complication rate. Recent research based on advanced imaging analysis, including quantitative computed tomography (QCT) and patient specific finite element (FE) modeling, has provided new and important insights into the magnitude and temporal pattern of bone loss, as well as the associated changes to bone structure and strength, following SCI. This work has illustrated the importance of early therapeutic treatment to prevent bone loss after SCI and may someday serve as the basis for a clinical fracture risk assessment tool for the SCI population. This review provides an update on the epidemiology of fracture after SCI and discusses new findings and significant developments related to bone loss and fracture risk assessment in the SCI population based on QCT analysis and patient-specific FE modeling. PMID- 26277793 TI - Interactions Between Bt-Bioinsecticides and Podisus nigrispinus (Dallas) (Hemiptera: Pentatomidae), a Predator of Plutella xylostella (L.) (Lepidoptera: Plutellidae). AB - Bioinsecticides are being increasingly used to protect vegetable crops against herbivores, but data on the side effects of such strategy on the third trophic level are still required. We investigated the influence of the Bacillus thuringiensis subsp. kurstaki HD-1 strain and of the commercial bioinsecticide Agree(r) on the biological aspects of the predator Podisus nigrispinus (Dallas) (Hemiptera: Pentatomidae) when feeding on Plutella xylostella (L.) (Lepidoptera: Plutellidae)-infected larvae. On average, infected larvae were consumed more often than the non-infected larvae throughout the predator nymphal development, and no effect on nymph survival was observed. Population growth parameters (R 0, r m, and lambda) resulting from the fertility life tables did not differ among treatments. The results led to the conclusion that P. nigrispinus can be used in combination with the product Agree(r) or the strain HD-1 for the control of P. xylostella. The combined use of these control agents helps to maintain the balance of the ecosystem and contributes for the production of food for healthy human consumption. PMID- 26277794 TI - [Reaction on 'The number of compulsory admissions continues to rise: Implications for the new Dutch law on obligatory mental health care']. PMID- 26277795 TI - Krishnan Chand Mahajan. PMID- 26277796 TI - The Motor Function Specialty. PMID- 26277797 TI - Preface: histone deacetylases as therapeutic targets. PMID- 26277798 TI - Chronic Q fever diagnosis- consensus guideline versus expert opinion AB - Chronic Q fever, caused by Coxiella burnetii, has high mortality and morbidity rates if left untreated. Controversy about the diagnosis of this complex disease has emerged recently. We applied the guideline from the Dutch Q Fever Consensus Group and a set of diagnostic criteria proposed by Didier Raoult to all 284 chronic Q fever patients included in the Dutch National Chronic Q Fever Database during 2006-2012. Of the patients who had proven cases of chronic Q fever by the Dutch guideline, 46 (30.5%)would not have received a diagnosis by the alternative criteria designed by Raoult, and 14 (4.9%) would have been considered to have possible chronic Q fever. Six patients with proven chronic Q fever died of related causes. Until results from future studies are available, by which current guidelines can be modified, we believe that the Dutch literature-based consensus guideline is more sensitive and easier to use in clinical practice. PMID- 26277799 TI - The Past Is Never Dead- Measles Epidemic, Boston, Massachusetts, 1713. PMID- 26277800 TI - Proceedings of the Rendez-Vous 2012 Conference: Community participation in health professional education, research and service, October 9-14, 2012, Thunder Bay, Canada. PMID- 26277801 TI - Influence of memory theme and posttraumatic stress disorder on memory specificity in British and Iranian trauma survivors. AB - This study investigated the influence of culture, memory theme and posttraumatic stress disorder (PTSD) on autobiographical memory specificity in Iranian and British trauma survivors. Participants completed the Autobiographical Memory Test and PTSD Diagnostic Scale. The results indicated that the British group provided significantly more personal-themed memories than the Iranian group, while the Iranian group provided significantly more social-themed memories than the British group. The British group also provided a significantly greater proportion of specific personal-themed and social-themed memories than the Iranian group. Overall, in both cultural groups memory specificity was found to be significantly correlated with PTSD symptoms. These findings provide further evidence that regardless of memory theme, specificity of autobiographical memories function to differentiate the self from others and reaffirm the independent self. They also further highlight that pan-culturally an overgeneral retrieval style may be employed by those with PTSD symptoms. PMID- 26277802 TI - In vivo Tube Assay: An Optimised Protocol of the Directed in vivo Angiogenesis Assay by Implementing Immunohistochemistry. AB - BACKGROUND: Angiogenesis, the formation of new blood vessels, is an essential process under physiological and pathological conditions. METHOD: Here, we improved the directed in vivo angiogenesis assay (DIVAA(r)) test, which is based on the usage of small Matrigel-filled tubes that are implanted into mice subcutaneously for a period of up to 15 days. The subsequent ex vivo assessment of neoangiogenesis within the silicon tubes is then achieved by fluorometry. RESULTS: We showed that the immunohistochemical quantification of the ingrowth of endothelial cells, based on CD31, was superior to the fluorometric quantification advised in the manufacturer's instructions. We optimised the explantation procedure, ensuring the complete recovery of the ingrown vessels. Using this modified protocol, we investigated the effect of the length of stay of the implanted tubes as well as of the concentration of the growth factors VEGF and FGF on the assay. CONCLUSION: Our improved protocol offered an effective and reliable alternative to the original assay, which is expected to facilitate in vivo research on angiogenesis and, thus, might drive the development of novel therapeutic agents. PMID- 26277803 TI - Pyrolysis-gas chromatography-mass spectrometry with electron-ionization or resonance-enhanced-multi-photon-ionization for characterization of polycyclic aromatic hydrocarbons in the Baltic Sea. AB - Polycyclic aromatic hydrocarbons (PAH), as a part of dissolved organic matter (DOM), are environmental pollutants of the marine compartment. This study investigates the origin of PAH, which is supposed to derive mainly from anthropogenic activities, and their alteration along the salinity gradient of the Baltic Sea. Pyrolysis in combination with gas chromatography and two mass selective detectors in one measurement cycle are utilized as a tool for an efficient trace analysis of such complex samples, by which it is possible to detect degradation products of high molecular structures. Along the north-south transect of the Baltic Sea a slightly rising trend for PAH is visible. Their concentration profiles correspond to the ship traffic as a known anthropogenic source, underlined by the value of special isomer ratios such as phenanthrene and anthracene (0.31-0.45) or pyrene and fluoranthene (0.44-0.53). The detection of naphthalene and the distribution of its alkylated representatives support this statement. PMID- 26277804 TI - In ovo exposure to organophosphorous flame retardants: survival, development, neurochemical, and behavioral changes in white leghorn chickens. AB - Organophosphorous flame retardants (OPFRs) are contaminants of emerging concern. There is growing evidence of environmental contamination and exposures to both humans and wildlife. Here, the objective was to increase understanding of the potential neurodevelopmental effects of two relevant OPFRs, TMPP (tri (methylphenyl) phosphate; a non-halogen-containing OPFR) and TDCIPP (tris (1,3 dichloro-isopropyl) phosphate; a halogen-containing OPFR) in an avian embryo/chick model. We injected white leghorn chicken eggs with a range of TMPP (0, 10, 100, and 1000 ng/g) or TDCIPP (0, 10, 100, 1000, 50,000 ng/g) concentrations at incubation day 0 exposing embryos throughout the ~21-day in ovo period. Hatching success was unaffected by TMPP, but TDCIPP-exposed chicks had higher early-incubation mortality in 100 and 50,000 ng/g groups. On 7-9-day-old chicks, we assessed behavior via tests concerning righting reflex, angled balance beams, gait patterns, wing flap reflex, and open field movements. Chicks exposed to 100 ng/g TDCIPP achieved 40% lower maximum velocity in the open field test than vehicle-exposed controls, while those exposed to 1000 ng/g TDCIPP achieved 20% higher maximum velocity than vehicle-exposed controls. Chicks exposed to 50,000 ng/g TDCIPP showed reduced righting response success. There were no dose- or treatment-related differences in angled beam, gait analysis, or wing flap reflex tests. Cerebrum hemispheres from 10-day-old chicks were examined for neurochemistry (acetylcholinesterase [AChE] activity and both nicotinic [nACh] and muscarinic [mACh] acetylcholine receptor levels) and cerebellums were examined for histopathology. TDCIPP-exposed chicks had reduced number of degenerate Purkinje cells (TDCIPP, 1000 ng/g), possibly indicating disruption of neurodevelopment. No neurochemical effects were found in TMPP- or TDCIPP-exposed chicks. In general this study shows some possible neurodevelopmental effects in chicks exposed to TDCIPP when levels greatly exceeded those measured in wild bird eggs and no clear changes in TMPP-exposed chicks. This study builds upon previous in vitro studies as well as work on adult birds showing that toxic responses in avian models can vary among species and OPFRs. PMID- 26277805 TI - Size Effects in the Interface Level Alignment of Dye-Sensitized TiO2 Clusters. AB - The efficiency of dye-sensitized solar cells (DSCs) depends critically on the electronic structure of the interfaces in the active region. We employ recently developed dispersion-inclusive density functional theory (DFT) and GW methods to study the electronic structure of TiO2 clusters sensitized with catechol molecules. We show that the energy level alignment at the dye-TiO2 interface is the result of an intricate interplay of quantum size effects and dynamic screening effects and that it may be manipulated by nanostructuring and functionalizing the TiO2. We demonstrate that the energy difference between the catechol LUMO and the TiO2 LUMO, which is associated with the injection loss in DSCs, may be reduced significantly by reducing the dimensions of nanostructured TiO2 and by functionalizing the TiO2 with wide-gap moieties, which contribute additional screening but do not interact strongly with the frontier orbitals of the TiO2 and the dye. Precise control of the electronic structure may be achieved via "interface engineering" in functional nanostructures. PMID- 26277806 TI - Light-Driven Hydrogen Production by Hydrogenases and a Ru-Complex inside a Nanoporous Glass Plate under Aerobic External Conditions. AB - Hydrogenases are powerful catalysts for light-driven H2 production using a combination of photosensitizers. However, except oxygen-tolerant hydrogenases, they are immediately deactivated under aerobic conditions. We report a light driven H2 evolution system that works stably even under aerobic conditions. A [NiFe]-hydrogenase from Desulfovibrio vulgaris Miyazaki F was immobilized inside nanoporous glass plates (PGPs) with a pore diameter of 50 nm together with a ruthenium complex and methyl viologen as a photosensitizer and an electron mediator, respectively. After immersion of PGP into the medium containing the catalytic components, an anaerobic environment automatically established inside the nanopores even under aerobic external conditions upon irradiation with solar simulated light; this system constantly evolved H2 with an efficiency of 3.7 MUmol H2 m(-2) s(-1). The PGP system proposed in this work represents a promising first step toward the development of an O2-tolerant solar energy conversion system. PMID- 26277807 TI - Surface Photovoltage Spectroscopy Study of Organo-Lead Perovskite Solar Cells. AB - The field of organo-lead perovskite absorbers for solar cells is developing rapidly, with open-circuit voltage of reported devices already approaching the maximal theoretical voltage. Obtaining such high voltages on spun-cast or evaporated thin films is intriguing and calls for detailed investigation of the source of photovoltage in those devices. We present here a study of the roles of the selective contacts to methylammonium lead iodide chloride (MAPbI3-xClx) using surface photovoltage spectroscopy. By depositing and characterizing each layer at a time, we show that the electron-extracting interface is more than twice as effective as the hole-extracting interface in generating photovoltage, for several combinations of electrode materials. We further observe the existence of an electron-injection related spectral feature at 1.1 eV, which might bear significance for the cell's operation. Our results illustrate the usefulness of SPV spectroscopy in highlighting gaps in cells efficiency and for deepening the understanding of charge injection processes in perovskite-based photovoltaics. PMID- 26277808 TI - Direct Dynamics Studies of a Binuclear Metal Complex in Solution: The Interplay Between Vibrational Relaxation, Coherence, and Solvent Effects. PMID- 26277809 TI - Solvent Degradation in Nonaqueous Li-O2 Batteries: Oxidative Stability versus H Abstraction. AB - Developing rechargeable Li-O2 batteries hinges on identifying stable solvents resistant to decomposition. Here, we focus on solvent stability against adsorption-induced H-abstraction during discharge. Using a detailed thermodynamic analysis, we show that a solvent's propensity to resist H-abstraction is determined by its acid dissociation constant, pKa, in its own environment. Upon surveying hundreds of solvents for their pKa values in different media, we find linear correlations between the pKa values across various classes of solvents in any two given media. Utilizing these correlations, we choose DMSO as the common standard to compare the relative stability trends. We construct a stability plot based on the solvent's HOMO level and its pKa in DMSO, which reveals that most solvents obey a correlation where solvents with lower HOMO levels tend to have lower pKa values in DMSO. However, this is at odds with the stability requirement that demands deep HOMO levels and high pKa values. Thus, stable solvents need to be outliers to this observed correlation. PMID- 26277810 TI - Acceleration of Singlet Fission in an Aza-Derivative of TIPS-Pentacene. AB - The influence of the carbon to nitrogen substitution on the photoinduced dynamics of TIPS-pentacene was investigated by ultrafast transient absorption measurements on spin-coated thin films in the visible and in the near-infrared spectral region. A global target analysis was performed to provide a detailed picture of the excited-state dynamics. We found that the chemical modification has a high impact on the triplet formation and leads to shorter dynamics; hence it speeds up the singlet fission process. A faster relaxation from the singlet into the triplet manifold implies a higher efficiency because other relaxation channels are avoided. The air-stable aza-derivatives have the potential to exceed the energy conversion efficiency of TIPS-pentacene. PMID- 26277811 TI - Dynamic Nuclear Polarization NMR of Low-gamma Nuclei: Structural Insights into Hydrated Yttrium-Doped BaZrO3. AB - We demonstrate that solid-state NMR spectra of challenging nuclei with a low gyromagnetic ratio such as yttrium-89 can be acquired quickly with indirect dynamic nuclear polarization (DNP) methods. Proton to (89)Y cross polarization (CP) magic angle spinning (MAS) spectra of Y(3+) in a frozen aqueous solution were acquired in minutes using the AMUPol biradical as a polarizing agent. Subsequently, the detection of the (89)Y and (1)H NMR signals from technologically important hydrated yttrium-doped zirconate ceramics, in combination with DFT calculations, allows the local yttrium and proton environments present in these protonic conductors to be detected and assigned to different hydrogen-bonded environments. PMID- 26277812 TI - Investigating Superoxide Transfer through a MU-1,2-O2 Bridge between Nonheme Ni(III)-Peroxo and Mn(II) Species by DFT Methods to Bridge Theoretical and Experimental Views. AB - Previously, a fast unprecedented O2(*-) transfer reaction has been observed experimentally when adding a Mn(II) complex into a solution containing a Ni(III) peroxo complex. Due to the fast reaction rate, no intermediates were observed. We have investigated this reaction with density functional theory (DFT) and show that DFT is unusually problematic in reproducing the correct spin state for the investigated Ni(III)-peroxo complex, something which calls for examination of all previous Ni-dioxygen studies. Surprisingly, the BP86 functional is shown to yield energies more in agreement with known experiments than B3LYP. The calculations reveal for the first time an intermediate structure in a complete O2(*-) transfer reaction, shown here to be a short-lived bridging Ni-(MU-1,2-O2)-Mn structure. PMID- 26277813 TI - Why Did You Accept My Paper? PMID- 26277814 TI - Phosphonic Acid Adsorbates Tune the Surface Potential of TiO2 in Gas and Liquid Environments. AB - Controlled attachment of molecules to the surface of a material can alter the band structure energies with respect to the surrounding environment via a combination of intrinsic and bonding-induced dipoles. Here, we demonstrate that the surface potential of an application-relevant material, anatase TiO2, can be tuned over a broad energy range of ~1 eV using a family of dipolar phosphonic acid-based adsorbates. Using TiO2 as an example, we show with photoelectron spectroscopy that these adsorbates are stable in a liquid environment (propylene carbonate). More interestingly, the tunability is substantially retained and follows trends in the computed bound dipole. The electrochemical surface potential is shown to vary over 600 meV, the highest range in electrolytes to the best of our knowledge. Using density functional theory calculations, we rationalize the measured trends and show that the effective dipole upon molecular adsorption and not the intrinsic dipole of the isolated molecules correlates with observed changes in surface potential. Control of the effective dipole, through judicious choice of robust surface species, can allow in situ tuning of energy levels and functionality at active surfaces for energy conversion and storage, biosensing, and molecular electronics. PMID- 26277815 TI - Exploiting Hydrophobic Interactions at the Nanoscale. AB - Hydrophobic effects are ubiquitous and manifest themselves in everyday processes such as solubilizing oil, precipitating molecules, and formation of particles or foam. Although this phenomenon is often intuitively recognized, it is not straightforward to predict it and, in particular, to control it experimentally. Hydrophobic effects are however progressively gaining recognition as an important tool providing control at the nanoscale, which may ultimately lead to the design of responsive metamaterials with unprecedented functionalities under nonequilibrium conditions. PMID- 26277816 TI - Excited-State Dynamics of Isolated and Microsolvated Cinnamate-Based UV-B Sunscreens. AB - Sunscreens are aimed at providing protection from solar UV radiation. However, the same mechanism that underlies this protection (absorption of UV radiation) is also responsible for their light-induced adverse effects. Here, high-resolution spectroscopic methods are applied to one of the most commonly used sunscreen chromophores to study the excited-state dynamics that determine the delicate balance between favorable and adverse effects. In contrast to common belief, we find that excitation to the "bright" pipi* state does not directly lead to repopulation of the electronic ground state. Instead, internal conversion to another electronically excited state identified as the "dark" npi* state is a major decay pathway that impedes fast energy dissipation. Microsolvation studies of sunscreen chromophores with water demonstrate that under such conditions, this bottleneck is no longer present. These observations could be a first step toward the development of sunscreens with improved photochemical properties. PMID- 26277817 TI - Spectroscopic Signature of Stacking Disorder in Ice I. AB - There is a growing realization that the presence of stacking disorder in ice I strongly influences its physical and chemical properties. Using Raman spectroscopy, we gain new fundamental insights into the spectroscopic properties of ice. We show that stacking disorder can be detected and quantified by comparing the spectra of stacking disordered ice with spectra of the "ordinary" hexagonal ice Ih. The spectral signature of stacking disorder is thought to arise from a greater structural diversity on the local length scale, vibrational modes that appear due to the lower-symmetry environments, and a strengthening of the covalent bonds. Our findings are compared to results from diffraction and calorimetry, and we discuss the advantages and disadvantages of the three techniques with respect to detecting stacking disorder in ice I. Apart from characterizing stacking disordered ice in the research lab, our new method is perfectly suited for remote or telescopic applications aiming at the identification of stacking disordered ice in nature. PMID- 26277818 TI - Activity-Stability Trends for the Oxygen Evolution Reaction on Monometallic Oxides in Acidic Environments. AB - In the present study, we used a surface-science approach to establish a functional link between activity and stability of monometallic oxides during the OER in acidic media. We found that the most active oxides (Au ? Pt < Ir < Ru ? Os) are, in fact, the least stable (Au ? Pt > Ir > Ru ? Os) materials. We suggest that the relationships between stability and activity are controlled by both the nobility of oxides as well as by the density of surface defects. This functionality is governed by the nature of metal cations and the potential transformation of a stable metal cation with a valence state of n = +4 to unstable metal cation with n > +4. A practical consequence of such a close relationship between activity and stability is that the best materials for the OER should balance stability and activity in such a way that the dissolution rate is neither too fast nor too slow. PMID- 26277819 TI - Investigation of the Redispersion of Pt Nanoparticles on Polyhedral Ceria Nanoparticles. AB - Redispersion of platinum nanoparticles (Pt NPs) on ceria is an important route for catalyst regeneration and antisintering. Here, we investigate the redispersion of Pt on ceria nanoparticles with defined surface planes including cubes ({100}) and octahedra ({111}). It is observed that Pt redispersion takes place only on ceria cubes in an alternating oxidation and reduction atmosphere. A quicker alternation rate is beneficial for such redispersion. On the basis of our experimental results and understandings toward this process, we proposed that the redispersion takes place at the moment of alternation of oxidation and reduction. PMID- 26277820 TI - Complex and Sustained Quantum Beating Patterns in a Classic IVR System: The 3(1)5(1) Level in S1 p-Difluorobenzene. AB - Using picosecond time-resolved photoelectron imaging, we have studied the intramolecular vibrational energy redistribution (IVR) dynamics that occur following the excitation of the 3(1)5(1) level, which lies 2068 cm(-1) above the S1 origin in p-difluorobenzene. Our technique, which has superior time resolution to that of earlier studies but retains sufficient energy resolution to identify the behavior of individual vibrational states, enables us to determine six distinct beating periods in photoelectron intensity, only one of which has been observed previously. Analysis shows that the IVR dynamics are restricted among only a handful of vibrational levels, despite the relatively high excitation energy. This is deduced to be a consequence of the high symmetry and rigid structure of p-difluorobenzene. PMID- 26277821 TI - Ultra-Low Thermal Conductivity in Organic-Inorganic Hybrid Perovskite CH3NH3PbI3. AB - We report on the temperature dependence of thermal conductivity of single crystalline and polycrystalline organometallic perovskite CH3NH3PbI3. The comparable absolute values and temperature dependence of the two samples' morphologies indicate the minor role of the grain boundaries on the heat transport. Theoretical modeling demonstrates the importance of the resonant scattering in both specimens. The interaction between phonon waves and rotational degrees of freedom of CH3NH3(+) sublattice emerges as the dominant mechanism for attenuation of heat transport and for ultralow thermal conductivity of 0.5 W/(Km) at room temperature. PMID- 26277822 TI - Association of interleukin 3 (IL-3) polymorphisms with schizophrenia in Han Chinese population. AB - Schizophrenia has been observed to be associated with various abnormalities in multiple cytokines. Recent genetic analyses showed that the interleukin 3 (IL-3) gene and its receptors are significantly associated with schizophrenia, especially in Irish populations. To examine the associations of the Irish-risk single nucleotide polymorphisms (SNPs, e.g., rs3916441) in the IL-3 gene with schizophrenia in Chinese population, we utilized two independent samples from Southwestern China, including a total 901 schizophrenia patients and 1417 healthy controls. However, no statistically significant differences were observed in allelic or genotypic frequencies of the tested 6 SNPs in IL-3 between cases and controls in any sample. Therefore, the results of our analyses were not able to confirm the association of IL-3 SNPs with schizophrenia. The absence of the IL 3's association in Chinese population suggest a potential genetic heterogeneity in the susceptibility of schizophrenia on this locus and also demonstrate the difficulties in replicating associations of schizophrenia across different ethnic populations. PMID- 26277823 TI - Preventive effects of ginsenoside Rg1 on post-traumatic stress disorder (PTSD) like behavior in male C57/B6 mice. AB - We investigated the preventive effects of Rg1 on a model of mouse post-traumatic stress disorder (PTSD) induced by electric shock combined with situation reminder and explored the underlying mechanism. In the experiment, before the PTSD animal model was developed, Rg1 (10, 5, and 2.5mg/kg) was orally administered for one week. After the animal model was established, PTSD-like behavior was observed using elevated plus maze, black and light box, and open field tests. One hour after the behavior test, all mice were sacrificed, and then serum corticosterone (CORT) and hypothalamus corticotrophin-releasing hormone (CRH) assays were performed. Results showed that Rg1 (5mg/kg) treatments relieved PTSD-like behavior by altering elevated serum corticosterone and hypothalamus CRH levels. By contrast, fluoxetine (3mg/kg) treatment reversed the behavior changes and had no effect on increased CORT and CRH levels. These findings confirmed the preventive effect of Rg1 in PTSD model. Decreasing CORT and CRH levels may be one of the underlying mechanisms. PMID- 26277824 TI - Does skin-to-skin contact and breast feeding at birth affect the rate of primary postpartum haemorrhage: Results of a cohort study. AB - OBJECTIVE: to examine the effect of skin-to-skin contact and breast feeding within 30 minutes of birth, on the rate of primary postpartum haemorrhage (PPH) in a sample of women who were at mixed-risk of PPH. DESIGN: retrospective cohort study. SETTING: two obstetric units plus a freestanding birth centre in New South Wales (NSW) Australia. PARTICIPANTS: after excluding women (n=3671) who did not have opportunity for skin to skin and breast feeding, I analysed birth records (n=7548) for the calendar years 2009 and 2010. Records were accessed via the electronic data base ObstetriX. INTERVENTION: skin to skin contact and breast feeding within 30 minutes of birth. MEASURES: outcome measure was PPH i.e. blood loss of 500ml or more estimated at birth. Data was analysed using descriptive statistics and logistic regression (unadjusted and adjusted). FINDINGS: after adjustment for covariates, women who did not have skin to skin and breast feeding were almost twice as likely to have a PPH compared to women who had both skin to skin contact and breast feeding (aOR 0.55, 95% CI 0.41-0.72, p<0.001). This apparently protective effect of skin to skin and breast feeding on PPH held true in sub-analyses for both women at 'lower' (OR 0.22, 95% CI 0.17-0.30, p<0.001) and 'higher' risk (OR 0.37 95% CI 0.24-0.57), p<0.001. KEY CONCLUSIONS AND IMPLICATION FOR PRACTICE: this study suggests that skin to skin contact and breastfeeding immediately after birth may be effective in reducing PPH rates for women at any level of risk of PPH. The greatest effect was for women at lower risk of PPH. The explanation is that pronurturance promotes endogenous oxytocin release. Childbearing women should be educated and supported to have pronurturance during third and fourth stages of labour. PMID- 26277825 TI - Hyperglycemia is associated with simultaneous alterations in electrical brain activity in youths with type 1 diabetes mellitus. AB - OBJECTIVE: To assess the association between hyperglycemia and electrical brain activity in type 1 diabetes mellitus (T1DM). METHODS: Nine youths with T1DM were monitored simultaneously and continuously by EEG and continuous glucose monitor system, for 40 h. EEG powers of 0.5-80 Hz frequency bands in all the different brain regions were analyzed according to interstitial glucose concentration (IGC) ranges of 4-11 mmol/l, 11-15.5 mmol/l and >15.5 mmol/l. Analysis of variance was used to examine the differences in EEG power of each frequency band between the subgroups of IGC. Analysis was performed separately during wakefulness and sleep, controlling for age, gender and HbA1c. RESULTS: Mean IGC was 11.49 +/- 5.26 mmol/l in 1253 combined measurements. IGC>15.5 mmol/l compared to 4-11 mmol/l was associated during wakefulness with increased EEG power of low frequencies and with decreased EEG power of high frequencies. During sleep, it was associated with increased EEG power of low frequencies in all brain areas and of high frequencies in frontal and central areas. CONCLUSIONS: Asymptomatic transient hyperglycemia in youth with T1DM is associated with simultaneous alterations in electrical brain activity during wakefulness and sleep. SIGNIFICANCE: The clinical implications of immediate electrical brain alterations under hyperglycemia need to be studied and may lead to adaptations of management. PMID- 26277826 TI - Effective presentation of health care performance information for consumer decision making: A systematic review. AB - OBJECTIVE: This systematic review synthesizes what is known about the effective presentation of health care performance information for consumer decision making. METHODS: Six databases were searched for articles published in English between September 2003 and April 2014. Experimental studies comparing consumers' responses to performance information when one or more presentation feature was altered were included. A thematic analysis was performed and practical guidelines derived. RESULTS: All 31 articles retained, the majority which tested responses to various presentations of health care cost and/or quality information, found that consumers better understand and make more informed choices when the information display is less complex. Simplification can be achieved by reducing the quantity of choices, displaying results in a positive direction, using non technical language and evaluative elements, and situating results in common contexts. CONCLUSION: While findings do not offer a prescriptive design, this synthesis informs approaches to enhancing the presentation of health care performance information and areas that merit additional research. PRACTICE IMPLICATIONS: Guidelines derived from these results can be used to enhance health care performance reports for consumer decision making including using recognizable, evaluative graphics and customizable formats, limiting the amount of information presented, and testing presentation formats prior to use. PMID- 26277827 TI - Physician behavioral adaptability: A model to outstrip a "one size fits all" approach. AB - OBJECTIVE: Based on a literature review, we propose a model of physician behavioral adaptability (PBA) with the goal of inspiring new research. PBA means that the physician adapts his or her behavior according to patients' different preferences. The PBA model shows how physicians infer patients' preferences and adapt their interaction behavior from one patient to the other. We claim that patients will benefit from better outcomes if their physicians show behavioral adaptability rather than a "one size fits all" approach. METHOD: This literature review is based on a literature search of the PsycINFO((r)) and MEDLINE((r)) databases. RESULTS: The literature review and first results stemming from the authors' research support the validity and viability of parts of the PBA model. There is evidence suggesting that physicians are able to show behavioral flexibility when interacting with their different patients, that a match between patients' preferences and physician behavior is related to better consultation outcomes, and that physician behavioral adaptability is related to better consultation outcomes. PRACTICE IMPLICATIONS: Training of physicians' behavioral flexibility and their ability to infer patients' preferences can facilitate physician behavioral adaptability and positive patient outcomes. PMID- 26277828 TI - CT26 murine colon carcinoma expressing the red fluorescent protein KillerRed as a highly immunogenic tumor model. AB - The development of tumor therapies based on the activation of antitumor immunity requires tumor models that are highly immunogenic. The immunologic response to fluorescent proteins, green fluorescent protein (GFP), or enhanced GFP (EGFP) was demonstrated in different cancer models. However, for live animal imaging, red and far-red fluorescent proteins are preferable, but their immunogenicity has not been studied. We assessed the immunogenicity of the red fluorescent protein, KillerRed (KR), in CT26 murine colon carcinoma. We showed a slower growth and a lower tumor incidence of KR-expressing tumors in comparison with nonexpressing ones. We found that KR-expressing lung metastases and rechallenged tumors were not formed in mice that had been surgically cured of KR-expressing primary tumors. The effect of low-dose cyclophosphamide (CY) treatment was also tested, as this is known to activate antitumor immune responses. The low-dose CY therapy of CT26-KR tumors resulted in inhibition of tumor growth and improved mouse survival. In summary, we have established a highly immunogenic tumor model that could be valuable for investigations of the mechanisms of antitumor immunity and the development of new therapeutic approaches. PMID- 26277829 TI - Complete pathologic response as a prognostic factor for squamous cell carcinoma of the oropharynx post-chemoradiotherapy. AB - INTRODUCTION: Chemoradiotherapy for squamous cell carcinoma of the oropharynx (SCCO) provides good results for locoregional disease control, with high rates of complete clinical and pathologic responses, mainly in the neck. OBJECTIVE: To determine whether complete pathologic response after chemoradiotherapy is related to the prognosis of patients with SCCO. METHODS: Data were prospectively extracted from clinical records of N2 and N3 SCCO patients submitted to a planned neck dissection after chemoradiotherapy. RESULTS: A total of 19 patients were evaluated. Half of patients obtained complete pathologic response in the neck. Distant or locoregional recurrence occurred in approximately 42% of patients, and 26% died. Statistical analysis showed an association between complete pathologic response and lower disease recurrence rate (77.8% vs. 20.8%; p=0.017) and greater overall survival (88.9% vs. 23.3%; p=0.049). CONCLUSION: The presence of a complete pathologic response after chemoradiotherapy positively influences the prognosis of patients with SCCO. PMID- 26277830 TI - Vestibular migraine: comparative analysis between diagnostic criteria. AB - INTRODUCTION: There is a strong association between vertigo and migraine. Vestibular migraine (VM) was described in 1999, and diagnostic criteria were proposed in 2001 and revised in 2012. OBJECTIVE: To compare the diagnostic criteria for VM proposed in 2001 with 2012 criteria with respect to their diagnostic power and therapeutic effect of VM prophylaxis. METHODS: Clinical chart review of patients attended to in a VM clinic. RESULTS: The 2012 criteria made the diagnosis more specific, restricting the diagnosis of VM to a smaller number of patients, such that 87.7% of patients met 2001 criteria and 77.8% met 2012 criteria. Prophylaxis for VM was effective both for patients diagnosed by either set of criteria and for those who did not meet any of the criteria. CONCLUSIONS: The 2012 diagnostic criteria for VM limited the diagnosis of the disease to a smaller number of patients, mainly because of the type, intensity, and duration of dizziness. Patients diagnosed with migraine and associated dizziness demonstrated improvement after prophylactic treatment of VM, even when they did not meet diagnostic criteria. PMID- 26277831 TI - Addendum to the history of cochlear implants in Brazil. PMID- 26277832 TI - Accuracy of peripheral arterial tonometry in the diagnosis of obstructive sleep apnea. AB - INTRODUCTION: The use of handheld devices that assess peripheral arterial tonometry has emerged as an auxiliary method for assessment and diagnosis of obstructive sleep apnea syndrome. OBJECTIVE: To evaluate the accuracy of peripheral arterial tonometry in the diagnosis of obstructive sleep apnea. METHODS: Contemporary cohort cross-sectional study. Thirty patients with suspected obstructive sleep apnea underwent peripheral arterial tonometry and assisted nocturnal polysomnography concomitantly. RESULTS: The mean apnea/hypopnea index by peripheral arterial tonometry was significantly higher than that by polysomnography (p<0.001), but the values of both sleep studies were significantly correlated (r=0.762). There was a high correlation between variables: minimum oxygen saturation (r=0.842, p<0.001), oxygen saturation<90% (r=0.799, p<0.001), and mean heart rate (r=0.951, p<0.001). Sensitivity and specificity were 60% and 96.2% (AUC: 0.727; p=0.113), respectively, when at a threshold value of 5 events/h. In severe cases (>=30 events/h), the result was a sensitivity of 77.8% and a specificity of 86.4% (AUC: 0.846, p=0.003). CONCLUSION: Peripheral arterial tonometry is a useful portable device for the diagnosis of obstructive sleep apnea; its accuracy is higher in moderate and severe cases. PMID- 26277833 TI - Association between maternal smoking, gender, and cleft lip and palate. AB - INTRODUCTION: Cleft lip and/or palate (CL/P) represent the most common congenital anomalies of the face. OBJECTIVE: To assess the relationship between maternal smoking, gender and CL/P. METHODS: This is an epidemiological cross-sectional study. We interviewed 1519 mothers divided into two groups: CASES: mothers of children with CL/P (n=843) and CONTROLS: mothers of children without CL/P (n=676). All mothers were classified as smoker or non-smoker subjects during the first trimester of pregnancy. To determine an association among maternal smoking, gender, and CL/P, odds ratios were calculated and the adjustment was made by a logistic regression model. RESULTS: An association between maternal smoking and the presence of cleft was observed. There was also a strong association between male gender and the presence of cleft (OR=3.51; 95% CI 2.83-4.37). By binary logistic regression analysis, it was demonstrated that both variables were independently associated with clefts. In a multivariate analysis, male gender and maternal smoking had a 2.5- and a 1.5-time greater chance of having a cleft, respectively. CONCLUSION: Our findings are consistent with a positive association between maternal smoking during pregnancy and CL/P in male gender. The results support the importance of smoking prevention and introduction of cessation programs among women with childbearing potential. PMID- 26277834 TI - Assessment of the light intensity of otoscopes utilized in teaching hospitals. AB - INTRODUCTION: To attain an accurate otoscopic diagnosis, a functioning device with adequate capacity must be used. OBJECTIVE: Evaluate the light intensity of otoscopes, comparing it utilizing the batteries present at the moment of calibration and after new batteries were supplied. METHODS: Cross-sectional study of a historical cohort, which assessed 38 otoscopes, measuring the light intensity with the batteries present at the moment of assessment compared to the intensity with new batteries, as well as charge of the test batteries and the new batteries. RESULTS: The mean of the sum of new batteries' charge was 3.19V, and of the test batteries was 2.70V, representing a decrease of 18.02% in charge. The mean luminosity with the new batteries was 366.89lumens, whereas in the test batteries it was 188.32lumens, representing a decrease of 83.75% in the light intensity. Student's t-test was applied for data comparison, showing a statistical difference between the light intensity with the original batteries and the new batteries (p=0.0001; CI=0.95). CONCLUSION: There was a statistically significant difference between the proportions of light intensity in the otoscopes. A small variation in battery charge results in a great variation in light. PMID- 26277835 TI - Waldenstrom's macroglobulinemia presenting with bilateral vestibular loss: a case report. PMID- 26277836 TI - Neonatal hearing screening in a low-risk maternity in Sao Paulo state. AB - INTRODUCTION: The literature indicates that neonatal hearing screening should be universal, so a description of programs that adopt this recommendation is relevant. OBJECTIVE: To describe the results of newborn hearing screening and the profile of mothers and newborns attended to in a low-risk maternity setting, and to correlate the characteristics of this population with the results of transient evoked otoacoustic emissions. METHODS: A contemporary cross-sectional cohort study. The sample consisted of 670 infants and the procedures performed were audiological history, transient-evoked otoacoustic emissions (TEOAE), distortion product-evoked otoacoustic emissions (DPEOAE), and automated-brainstem auditory evoked potential (ABSAEP). RESULTS: The rate of success in this program was 98.5%, the failure rate was 0.62%, and that of non-attendance to finalize the diagnostic process, 0.93%. When correlating the variables studied with the results of transient evoked otoacoustic emissions, there was a significant negative correlation only for age of infant. CONCLUSION: The program of this maternity hospital was effective and complies with national and international recommendations. The population consisted of young mothers with few pregnancy complications and healthy infants. The only variable that influenced transient evoked otoacoustic emission results, after hospital discharge, was the age at which infants were evaluated. PMID- 26277837 TI - Comment on Choi et al.: High-fat diet decreases energy expenditure and expression of genes controlling lipid metabolism, mitochondrial function and skeletal system development in the adipose tissue, along with increased expression of extracellular matrix remodelling- and inflammation-related genes. PMID- 26277838 TI - Asparagine attenuates intestinal injury, improves energy status and inhibits AMP activated protein kinase signalling pathways in weaned piglets challenged with Escherichia coli lipopolysaccharide. AB - The intestine requires a high amount of energy to maintain its health and function; thus, energy deficits in intestinal mucosa may lead to intestinal damage. Asparagine (Asn) is a precursor for many other amino acids such as aspartate, glutamine and glutamate, which can be used to supply energy to enterocytes. In the present study, we hypothesise that dietary supplementation of Asn could alleviate bacterial lipopolysaccharide (LPS)-induced intestinal injury via improvement of intestinal energy status. A total of twenty-four weaned piglets were assigned to one of four treatments: (1) non-challenged control; (2) LPS+0 % Asn; (3) LPS+0.5 % Asn; (4) LPS+1.0 % Asn. On day 19, piglets were injected with LPS or saline. At 24 h post-injection, piglets were slaughtered and intestinal samples were collected. Asn supplementation improved intestinal morphology, indicated by higher villus height and villus height:crypt depth ratio, and lower crypt depth. Asn supplementation also increased the ratios of RNA:DNA and protein:DNA as well as disaccharidase activities in intestinal mucosa. In addition, Asn supplementation attenuated bacterial LPS-induced intestinal energy deficits, indicated by increased ATP and adenylate energy charge levels, and decreased AMP:ATP ratio. Moreover, Asn administration increased the activities of key enzymes involved in the tricarboxylic acid cycle, including citrate synthase, isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase complex. Finally, Asn administration decreased the mRNA abundance of intestinal AMP-activated protein kinase-alpha1 (AMPKalpha1), AMPKalpha2, silent information regulator 1 (SIRT1) and PPARgamma coactivator-1alpha (PGC1alpha), and reduced intestinal AMPKalpha phosphorylation. Collectively, these results indicate that Asn supplementation alleviates bacterial LPS-induced intestinal injury by modulating the AMPK signalling pathway and improving energy status. PMID- 26277839 TI - Regulation of Expression of Renal Organic Anion Transporters OAT1 and OAT3 in a Model of Ischemia/Reperfusion Injury. AB - BACKGROUND: Recently, we gained evidence that impairment of rOat1 and rOat3 expression induced by ischemic acute kidney injury (AKI) is mediated by COX metabolites and this suppression might be critically involved in renal damage. METHODS: (i) Basolateral organic anion uptake into proximal tubular cells after model ischemia and reperfusion (I/R) was investigated by fluorescein uptake. The putative promoter sequences from hOAT1 (SLC22A6) and hOAT3 (SCL22A8) were cloned into a reporter plasmid, transfected into HEK cells and (ii) transcriptional activity was determined after model ischemia and reperfusion as a SEAP reporter gen assay. Inhibitors or antagonists were applied with the beginning of reperfusion. RESULTS: By using inhibitors of PKA (H89) and PLC (U73122), antagonists of E prostanoid receptor type 2 (AH6809) and type 4 (L161,982), we gained evidence that I/R induced down regulation of organic anion transport is mediated by COX1 metabolites via E prostanoid receptor type 4. The latter signaling was confirmed by application of butaprost (EP2 agonist) or TCS2510 (EP4 agonist) to control cells. In brief, the latter signaling was verified for the transcriptional activity in the reporter gen assay established. Therein, selective inhibitors for COX1 (SC58125) and COX2 (SC560) were also applied. CONCLUSION: Our data show (a) that COX1 metabolites are involved in the regulation of renal organic anion transport(ers) after I/R via the EP4 receptor and (b) that this is due to transcriptional regulation of the respective transporters. As the promoter sequences cloned were of human origin and expressed in a human renal epithelial cell line we (c) hypothesize that the regulatory mechanisms described after I/R is meaningful for humans as well. PMID- 26277841 TI - Damage to the Median and Ulnar Nerves After a Snake Bite. PMID- 26277840 TI - Chronic fetal exposure to caffeine altered resistance vessel functions via RyRs BKCa down-regulation in rat offspring. AB - Caffeine modifies vascular/cardiac contractility. Embryonic exposure to caffeine altered cardiac functions in offspring. This study determined chronic influence of prenatal caffeine on vessel functions in offspring. Pregnant Sprague-Dawley rats (5-month-old) were exposed to high dose of caffeine, their offspring (5 month-old) were tested for vascular functions in mesenteric arteries (MA) and ion channel activities in smooth muscle cells. Prenatal exposure to caffeine increased pressor responses and vasoconstrictions to phenylephrine, accompanied by enhanced membrane depolarization. Large conductance Ca2(+)-activated K(+) (BKCa) channels in buffering phenylephrine-induced vasoconstrictions was decreased, whole cell BKCa currents and spontaneous transient outward currents (STOCs) were decreased. Single channel recordings revealed reduced voltage/Ca(2+) sensitivity of BKCa channels. BKCa alpha-subunit expression was unchanged, BKCa beta1-subunit and sensitivity of BKCa to tamoxifen were reduced in the caffeine offspring as altered biophysical properties of BKCa in the MA. Simultaneous [Ca(2+)]i fluorescence and vasoconstriction testing showed reduced Ca(2+), leading to diminished BKCa activation via ryanodine receptor Ca(2+) release channels (RyRs), causing enhanced vascular tone. Reduced RyR1 was greater than that of RyR3. The results suggest that the altered STOCs activity in the caffeine offspring could attribute to down-regulation of RyRs-BKCa, providing new information for further understanding increased risks of hypertension in developmental origins. PMID- 26277842 TI - Interhemispheric Vertical Hemispherotomy: A Single Center Experience. AB - PURPOSE: Hemispheric epileptogenic lesions such as hemimegalencephaly often manifest as intractable epilepsy in early infancy. Hemispherotomy is the treatment of choice for controlling intractable hemispheric epilepsy. Less invasive procedures are desirable for surgery on infants with low body weight. This study compared our experience with interhemispheric vertical hemispherotomy (IVH) and peri-insular lateral hemispherotomy (PIH). METHODS: Thirteen consecutive patients underwent hemispherotomy for treatment of intractable epilepsy in our institution between 2001 and 2012. The etiology of epilepsy included hemimegalencephaly in 7 patients and cortical dysplasia in 3. PIH was performed on the first 5 patients and IVH on the last 8 patients. In the latter procedure, complete section of the corpus callosum was first performed via the interhemispheric approach. After removing part of the cingulate gyrus, section of the descending fibers was performed anterolaterally to the thalamus. Clinical characteristics, duration of operation and amount of blood transfusion were compared between the PIH and IVH groups. RESULTS: There was no difference in age at surgery, body weight and age of epilepsy onset between the two groups. No surgery-related death was observed. No patients required shunt operation. One patient who underwent IVH required reoperation for incomplete disconnection. The amount of intraoperative blood transfusion was smaller and the total duration of operation was shorter in the IVH group than in the PIH group. CONCLUSION: The interhemispheric approach minimizes cortical resection and may be less invasive than PIH. IVH is advantageous for treating infants with low body weight. PMID- 26277844 TI - Long-Term Mortality among Hospitalized Non-ICU Patients with Acute Kidney Injury Referred to Nephrology. AB - BACKGROUND: Epidemiological studies of acute kidney injury (AKI) have focused on patients admitted to intensive care units (ICUs), and several have studied hospitalized non-ICU patients, but analysis of patients referred to Nephrology is sparse. We analyzed factors associated with short- and long-term morbimortality among hospitalized non-ICU patients with AKI who were referred to Nephrology. METHODS: A retrospective study with data prospectively collected from 170 non-ICU patients, with referral to the Nephrology Unit, recruited over a 4-year period, was performed. AKI was classified according to the criteria based on risk, injury, failure, loss of kidney function and end-stage kidney disease (RIFLE). Risk factors that could influence prognosis of AKI and long-term mortality were analyzed at admission. Early on, 1- and 10-year mortalities were correlated with AKI RIFLE class, clinical and demographic characteristics. RESULTS: Most patients were >65 years, with multiple comorbidities and frequent drug intake history. Median Charlson score was 6. Twenty-five percent of patients with previously unknown chronic kidney disease (CKD) were diagnosed with CKD during the study. Dialysis was required in 13.5% of patients. Hospital deaths were 22.4% and significantly associated with older age, RIFLE class L, higher peak serum creatinine, oliguria and decreased serum albumin levels. One-year (38.8%) and 10 year (68.8%) mortalities were significantly associated with age, prior cardiovascular disease, prior CKD and RIFLE class L. According to the Cox proportional hazard model, age, prior CKD and RIFLE class L were independent risk factors of death at 1 and 10 years. CONCLUSIONS: AKI in hospitalized non-ICU patients is associated with high early and late mortality. This study increases our understanding of AKI among this specific population and can improve their management. PMID- 26277845 TI - Criteria for Selecting an Optimal Device for the Contralateral Ear of Children with a Unilateral Cochlear Implant. AB - OBJECTIVE: To identify clinical criteria for selecting the aiding device for the contralateral ear of children with a unilateral cochlear implant (CI). METHODS: Sixty-five children, including 36 bilateral CI users and 29 bimodal users, participated in the study. A speech perception test (monosyllabic word test) in noise was administered. The target speech (65 dB sound pressure level) was presented from the front loudspeaker, and noise (10 dB signal-to-noise ratio) was presented from 3 directions: from in front of the child and 90 degrees to the child's right and left sides. The test was performed using the first CI alone and under bilateral CI or bimodal conditions. The bilateral benefits to speech perception in noise were compared between bilateral CI users and bimodal users. RESULTS: Significant benefits in speech perception in noise were evident in bilateral CI users in all 3 noise conditions. In bimodal users, the hearing threshold at low frequencies of <=1 kHz in the nonimplanted ear affected the bilateral benefit. Bimodal users with a low-frequency hearing threshold <=90 dB hearing level (HL) showed a significant bilateral benefit in various noise conditions. By contrast, bimodal users with a low-frequency hearing threshold >90 dB HL showed no significant bilateral benefits in all 3 noise conditions. CONCLUSIONS: Bilateral CI and bimodal listening provide better speech perception in noise than unilateral CI alone in children. The contralateral CI is better than bimodal listening for children with a low-frequency hearing threshold >90 dB HL. A hearing threshold at low frequencies of <=1 kHz may be a good criterion for deciding on the type of device for the contralateral ear of children with a unilateral CI. PMID- 26277846 TI - DXA and QCT Fracture Risk Assessment Beyond BMD. PMID- 26277847 TI - Executive Summary of the 2015 ISCD Position Development Conference on Advanced Measures From DXA and QCT: Fracture Prediction Beyond BMD. AB - There have been many scientific advances in fracture risk prediction beyond bone density. The International Society for Clinical Densitometry (ISCD) convened a Position Development Conference (PDC) on the use of dual-energy X-ray absorptiometry beyond measurement of bone mineral density for fracture risk assessment, including trabecular bone score and hip geometry measures. Previously, no guidelines for nonbone mineral density DXA measures existed. Furthermore, there have been advances in the analysis of quantitative computed tomography (QCT) including finite element analysis, QCT of the hip, DXA equivalent hip measurements, and opportunistic screening that were not included in the previous ISCD positions. The topics and questions for consideration were developed by the ISCD Board of Directors and the Scientific Advisory Committee and were designed to address the needs of clinical practitioners. Three task forces were created and asked to conduct comprehensive literature reviews to address specific questions. The task forces included participants from many countries and a variety of interests including academic institutions and private health care delivery organizations. Representatives from industry participated as consultants to the task forces. Task force reports with proposed position statements were then presented to an international panel of experts with backgrounds in bone densitometry. The PDC was held in Chicago, Illinois, USA, contemporaneously with the Annual Meeting of the ISCD, February 26 through February 28, 2015. This Executive Summary describes the methodology of the 2015 PDC on advanced measures from DXA and QCT and summarizes the approved official positions. Six separate articles in this issue will detail the rationale, discussion, and additional research topics for each question the task forces addressed. PMID- 26277848 TI - Fracture Risk Prediction by Non-BMD DXA Measures: the 2015 ISCD Official Positions Part 1: Hip Geometry. AB - Bone mineral density (BMD) measured by dual-energy X-ray absorptiometry is the current imaging procedure of choice to assess fracture risk. However, BMD is only one of the factors that explain bone strength or resistance to fracture. Other factors include bone microarchitecture and macroarchitecture. We now have the ability to assess some of these non-BMD parameters from a dual-energy X-ray absorptiometry image. Available measurements include various measurements of hip geometry including hip structural analysis, hip axis length, and neck-shaft angle. At the 2015 Position Development Conference, the International Society of Clinical Densitometry established official positions for the clinical utility of measurements of hip geometry. We present the official positions approved by an expert panel after careful review of the recommendations and evidence prepared by an independent task force. Each question addressed by the task force is presented followed by the official position with the associated medical evidence and rationale. PMID- 26277849 TI - Fracture Risk Prediction by Non-BMD DXA Measures: the 2015 ISCD Official Positions Part 2: Trabecular Bone Score. AB - Bone mineral density (BMD) as measured by dual-energy X-ray absorptiometry (DXA) is the gold standard for the diagnosis and management of osteoporosis. However, BMD explains only 60%-80% of bone strength, and a number of skeletal features other than BMD contribute to bone strength and fracture risk. Advanced imaging modalities can assess some of these skeletal features, but compared to standard DXA, these techniques have higher costs and limited accessibility. A major challenge, therefore, has been to incorporate in clinical practice a readily available, noninvasive technology that permits improvement in fracture-risk prediction beyond that provided by the combination of standard DXA measurements and clinical risk factors. To this end, trabecular bone score (TBS), a gray-level textural index derived from the lumbar spine DXA image, has been investigated. The purpose of this International Society for Clinical Densitometry task force was to review the evidence and develop recommendations on how to incorporate TBS in clinical practice. Clinical applications of TBS for fracture risk assessment, treatment initiation, monitoring of treatment, and use of TBS in special conditions related to greater fracture risk, were addressed. We present the official positions approved by an expert panel following careful review of the recommendations and evidence presented by the TBS task force. PMID- 26277850 TI - Measurement of Hip Geometry-Technical Background. AB - Conventional dual-energy X-ray absorptiometry images display a digital projection of the inorganic mineral mass in a scanned region. Bone mineral density software generates an average of the pixels within one or more regions. Although not used in the conventional analysis, the images also contain dimensional information limited to the plane of the image. The hip structure analysis method and that of the similar GE, Madison, WI, algorithm Advanced Hip Analysis use both the dimensional information and the mineral mass data to compute the types of dimensional properties (i.e., geometry) that are used to evaluate mechanical strength in engineering analyses. This article describes the hip structure analysis method and a somewhat cruder geometry approximation that does not require a reanalysis of the image. Limitations of the methods are discussed. PMID- 26277851 TI - Clinical Use of Quantitative Computed Tomography (QCT) of the Hip in the Management of Osteoporosis in Adults: the 2015 ISCD Official Positions-Part I. AB - The International Society for Clinical Densitometry (ISCD) has developed new official positions for the clinical use of quantitative computed tomography of the hip. The ISCD task force for quantitative computed tomography reviewed the evidence for clinical applications and presented a report with recommendations at the 2015 ISCD Position Development Conference. Here, we discuss the agreed on ISCD official positions with supporting medical evidence, rationale, controversy, and suggestions for further study. Parts II and III address the advanced techniques of finite element analysis applied to computed tomography scans and the clinical feasibility of existing techniques for opportunistic screening of osteoporosis using computed tomography scans obtained for other diagnosis such as colonography was addressed. PMID- 26277852 TI - Clinical Use of Quantitative Computed Tomography-Based Finite Element Analysis of the Hip and Spine in the Management of Osteoporosis in Adults: the 2015 ISCD Official Positions-Part II. AB - The International Society for Clinical Densitometry (ISCD) has developed new official positions for the clinical use of quantitative computed tomography (QCT) based finite element analysis of the spine and hip. The ISCD task force for QCT reviewed the evidence for clinical applications and presented a report with recommendations at the 2015 ISCD Position Development Conference. Here we discuss the agreed upon ISCD official positions with supporting medical evidence, rationale, controversy, and suggestions for further study. Parts I and III address the clinical use of QCT of the hip, and the clinical feasibility of existing techniques for opportunistic screening of osteoporosis using CT scans obtained for other diagnosis such as colonography was addressed. PMID- 26277853 TI - Clinical Use of Quantitative Computed Tomography-Based Advanced Techniques in the Management of Osteoporosis in Adults: the 2015 ISCD Official Positions-Part III. AB - The International Society for Clinical Densitometry (ISCD) has developed new official positions for the clinical use of computed tomography (CT) scans acquired without a calibration phantom, for example, CT scans obtained for other diagnosis such as colonography. This also addresses techniques suggested for opportunistic screening of osteoporosis. The ISCD task force for quantitative CT reviewed the evidence for clinical applications of these new techniques and presented a report with recommendations at the 2015 ISCD Position Development Conference. Here we discuss the agreed upon ISCD official positions with supporting medical evidence, rationale, controversy, and suggestions for further study. Advanced techniques summarized as statistical parameter mapping methods were also reviewed. Their future use is promising but the clinical application is premature. The clinical use of QCT of the hip is addressed in part I and of finite element analysis of the hip and spine in part II. PMID- 26277854 TI - A Long-Term Study to Evaluate Acidic Skin Care Treatment in Nursing Home Residents: Impact on Epidermal Barrier Function and Microflora in Aged Skin. AB - BACKGROUND: The pH of the stratum corneum (SC) in the elderly is elevated and linked to impaired SC function. Therefore, this paper addresses the question of whether acidic skin care generates positive clinical, biophysical, and microbiological effects in aged skin. METHODS: This study was performed to assess skin care effects in nursing home residents (aged 80-97 years). Visual, biophysical, and microbiological methods were used. Subjects were randomly assigned to 1 of 2 groups and treated over 7 weeks with skin care products adjusted to a pH of 4.0 (group A) or a pH of 6.0 (group B). RESULTS: Compared to baseline, SC integrity improved significantly in group A (p = 0.007), whereas there was no change in group B (p = 0.672). SC recovery 24 h after perturbation increased significantly in group A (p = 0.004) compared to baseline. The SC recovery in group B was not significant compared to baseline (p = 0.327). CONCLUSION: Long-term treatment with pH 4.0 skin care results in a significant improvement in epidermal barrier function compared to identical products with a pH of 6.0. In addition, effects on skin dryness and resident flora were demonstrated, but without significant differences, between the 2 groups. Based on these results, we recommend adjustment of skin care products for the elderly to a pH of 4.0 to maintain the health of aged skin. (c) 2015 S. Karger AG, Basel. PMID- 26277855 TI - CT-based delineation of organs at risk in the head and neck region: DAHANCA, EORTC, GORTEC, HKNPCSG, NCIC CTG, NCRI, NRG Oncology and TROG consensus guidelines. AB - PURPOSE: The objective of this project was to define consensus guidelines for delineating organs at risk (OARs) for head and neck radiotherapy for routine daily practice and for research purposes. METHODS: Consensus guidelines were formulated based on in-depth discussions of a panel of European, North American, Asian and Australian radiation oncologists. RESULTS: Twenty-five OARs in the head and neck region were defined with a concise description of their main anatomic boundaries. The Supplemental material provides an atlas of the consensus guidelines, projected on 1mm axial slices. The atlas can also be obtained in DICOM-RT format on request. CONCLUSION: Consensus guidelines for head and neck OAR delineation were defined, aiming to decrease interobserver variability among clinicians and radiotherapy centers. PMID- 26277856 TI - Effect of MLC tracking latency on conformal volumetric modulated arc therapy (VMAT) plans in 4D stereotactic lung treatment. AB - BACKGROUND AND PURPOSE: The latency of a multileaf collimator (MLC) tracking system used to overcome respiratory motion causes misalignment of the treatment beam with respect to the gross tumour volume, which may result in reduced target coverage. This study investigates the magnitude of this effect. MATERIAL AND METHODS: Simulated superior-inferior breathing motion was used to construct histograms of isocentre offset with respect to the gross tumour volume (GTV) for a variety of tracking latencies. Dose distributions for conformal volumetric modulated arc therapy (VMAT) arcs were then calculated at a range of offsets and summed according to these displacement histograms. The results were verified by delivering the plans to a Delta(4) phantom on a motion platform. RESULTS: In the absence of an internal target margin, a tracking latency of 150 ms reduces the GTV D95% by approximately 2%. With a margin of 2 mm, the same drop in dose occurs for a tracking latency of 450 ms. Lung V(13Gy) is unaffected by a range of latencies. These results are supported by the phantom measurements. CONCLUSIONS: Assuming that internal motion can be modelled by a rigid translation of the patient, MLC tracking of conformal VMAT can be effectively accomplished in the absence of an internal target margin for substantial breathing motion (4 s period and 20 mm peak-peak amplitude) so long as the system latency is less than 150 ms. PMID- 26277857 TI - Unraveling estradiol metabolism and involvement in the reproductive cycle of non vertebrate animals: The sea urchin model. AB - Estradiol (E2) is a well-known hormone in vertebrates whereas in invertebrates its unambiguous presence was verified only in some species. Weather this presence is also associated to similarly conserved roles in animal phylogeny is similarly uncertain. Due to their phylogenetic position, echinoderms represent ideal experimental models to provide evolutionary insights into estrogen appearance and function. Therefore, in this research, we investigated if E2 is truly present and has a role in the reproductive biology of the sea urchin Paracentrotus lividus. Presence of 17beta estradiol in body fluids was confirmed by liquid chromatography-mass spectrometry. By immunological methods (RIA) we evaluated the physiological circulating E2 levels of adult specimens and, on the basis of these, we directly administered E2 to study its metabolism and its putative effects on gonad development at physiological doses. Although different E2 tested concentrations, a correspondent dose-dependent increase of hormone levels was not found in both body fluids and gonads, suggesting the presence of potent homeostatic/detoxification mechanisms. These latter do not involve enzymes such as aromatase-like, sulfotransferase-like and acyltransferase-like, whose activities were not affected by E2 administration. Despite the increase of endogenous E2, the treatment did not induce significant variations in none of the considered reproductive parameters. Overall, this research (1) provides definitive evidence of E2 presence in sea urchin tissues and (2) demonstrate that, differently from vertebrates and starfish, E2 does not play a key role in sea urchins reproductive processes. Intra-phylum differences suggest the existence of class-specific hormonal mechanisms and highlight the risk of Phylum generalization. PMID- 26277858 TI - World Trade Center dust-inhalation: assessing the fallout. PMID- 26277859 TI - Cuba's complex respiratory picture. PMID- 26277860 TI - Health impacts of Facebook usage and mobile texting among undergraduate dental students: it's time to understand the difference between usage and an excessive use. AB - BACKGROUND: Facebook and mobile texting are prevalent in the lives of almost every student. However, little is known about the relationship between Facebook usage or mobile texting and their impacts on health amongst undergraduate dental students. In this study, excessive Facebook use and excessive mobile texting were studied as they relate to impacts on health. MATERIALS AND METHODS: A cross sectional study was conducted at a private university in Malaysia. A total of 188 undergraduate dental students were interviewed using a pre-tested and self-rated questionnaire. Data collected from participants were analysed using SPSS version 18.0. Chi-square test, Fisher's exact test and multiple logistic regression analyses were applied to study the relationship between explanatory variables and excessive Facebook use and excessive mobile texting. RESULTS: The prevalence of excessive Facebook use and excessive mobile texting amongst undergraduate dental students was found to be 33.2% and 33.0%, respectively. According to a multivariate analysis, texting habits, such as the presence of daytime sleepiness after texting late at night (aOR = 2.682, 95% CI = 1.142-6.301) and the presence of anxious feelings if students failed to receive a timely response (aOR = 3.819, 95% CI = 1.580-9.230), were determined to be significant predictors of excessive mobile texting. Excessive Facebook use was found to be significantly related to three variables as follows: fewer numbers of close friends (aOR = 2.275, 95% CI = 1.057-4.898), the checking of updates on the Facebook walls of their friends (aOR = 2.582, 95% CI = 1.189-5.605) and the absence of active and vigorous feelings during Facebook use (aOR = 3.401, 95% CI = 1.233-9.434). CONCLUSIONS: Approximately one-third of undergraduate dental students in this study experienced excessive Facebook use and/or excessive mobile texting. Health education and promotion should be instituted to create awareness, whilst students should be advised to practise self-control with respect to both mobile texting and Facebook usage. PMID- 26277861 TI - Synthesis and spectroscopic characterization of group 4 post-metallocenes bearing (sigma-aryl)-2-phenolate-6-pyridyl and -isoquinolinyl auxiliaries. AB - A new series of group 4 bis(benzyl) complexes supported by (sigma-aryl)-2 phenolate-6-pyridyl [O,C,N] ligands have been prepared, and all derivatives have been characterized by multinuclear NMR spectroscopy. In the (1)H NMR spectrum of the Ti derivative where [N] = (ortho-F)-substituted isoquinolinyl, one of the two CH2 resonances is observed as a doublet of doublets (collapsing to a normal d upon (19)F-decoupling), whereas the [(1)H,(19)F]-HMQC correlation spectrum reveals a strong crosspeak for this dd resonance only, thus indicating the presence of intramolecular C-HF-C interactions. [(1)H,(19)F]-HMBC experiments have been performed which reveal a significant scalar component for this coupling and confirm that the interactions are genuine. The contrasting NMR spectral patterns for the (ortho-F)-pyridyl Hf analogue, which exhibits two sets of non identical doublet of doublets for the methylene resonances, have been rationalized. The activities of the isoquinolinyl-based Ti-[O,C,N] catalysts for ethylene polymerization are superior to those of pyridyl-based congeners. PMID- 26277862 TI - Proven isolation of the pulmonary vein antrum with or without left atrial posterior wall isolation in patients with persistent atrial fibrillation. AB - BACKGROUND: It is unclear whether isolation of the left atrial posterior wall (LAPW) offers additional benefits over pulmonary vein antrum isolation (PVAI) alone in patients with persistent atrial fibrillation (AF). OBJECTIVE: We sought to determine the impact of PVAI and LAPW isolation (PVAI+LAPW) versus PVAI alone on the outcome of ablation of persistent AF. METHODS: During the first procedure, PVAI was performed in 20 patients (group 1), whereas in 32 patients (group 2), PVAI was extended to the left atrial (LA) septum and coronary sinus (CS), and isolation of the LAPW was targeted (ePVAI+LAPW). Isolation of the superior vena cava was achieved in both groups. All patients, regardless of arrhythmia recurrence, underwent a second procedure 3 months after the first procedure. In patients with reconnection of pulmonary veins or LAPW, reisolation was performed, and a third procedure was performed 3 months later to verify isolation. Patients entered follow-up only after PVAI (group 1) or PVAI+LAPW (group 2) isolation was proven. RESULTS: At the 1-, 2-, and 3-year follow-up examinations, the rates of freedom from atrial tachyarrhythmia without use of an antiarrhythmic drug were 20%, 15%, and 10% in group 1 and 65%, 50%, and 40% in group 2, respectively (log rank P < .001). The median recurrence-free survival time was 8.5 months (interquartile range 6.5-11.0) in group 1 and 28.0 months (interquartile range 8.5-32.0) in group 2. CONCLUSION: Proven isolation of the LAPW provides additional benefits over PVAI alone in the treatment of persistent AF and improves procedural outcome at follow-up. However, the ablation strategy of ePVAI+LAPW is still associated with a significant high incidence of very late recurrence of atrial tachyarrhythmia. CLINICAL TRIAL REGISTRATION: "Outcome of Atrial Fibrillation Ablation After Permanent Pulmonary Vein Antrum Isolation With or Without Proven Left Atrial Posterior Wall Isolation" (LIBERATION). ClinicalTrials.gov Identifier: NCT01660100. PMID- 26277863 TI - Contemporary rates of appropriate shock therapy in patients who receive implantable device therapy in a real-world setting: From the Israeli ICD Registry. AB - BACKGROUND: Implantable cardioverter-defibrillators (ICDs) have become the mainstay of preventive measures for sudden cardiac death (SCD). However, there are limited data on rates of appropriate life-saving ICD shock therapies in contemporary real-life settings. OBJECTIVE: The purpose of the study was to evaluate the rate of appropriate life-saving ICD shock therapies in a contemporary registry. METHODS: The Israeli ICD Registry includes all implants and other ICD operative procedures nationwide. The present study comprises 2349 consecutive cases who were enrolled in the Registry and prospectively followed up for information regarding survival, hospitalizations, and ICD therapies since 2010. RESULTS: Kaplan-Meier survival analysis showed that the rate of appropriate ICD shock therapy at 30-month follow-up was 2.6% among patients who received an ICD for primary prevention compared with 7.4% among those who received a device for secondary prevention (log-rank P < .001). Rates of appropriate ICD shocks among primary prevention patients were 1.1% at 1-year of follow-up and 2.6% at 30 months, whereas the corresponding rates in the secondary prevention group were 3.8% at 1 year and 7.4% at 30 months (log-rank P < .001). A total of 253 patients (4.8%) died during follow-up, 65% of noncardiac causes. CONCLUSION: Rates of life saving appropriate ICD shock therapies among patients implanted with a defibrillator for the primary prevention of SCD in a contemporary real-world setting are lower than reported previously. These findings suggest a need for improved risk stratification and patient selection in this population. PMID- 26277864 TI - Economic losses related to internal diseases in Japanese black cattle. AB - The objective of this study was to estimate the direct economic losses due to the condemnation of the liver and large intestine because of internal diseases (multifocal necrosis in the liver (MNL) and inflammation of the large intestine (ILI)), and the indirect losses because of reductions in carcass performance from MNL, bovine abdominal fat necrosis (BFN) and ILI using data from 5383 Japanese Black cattle. Direct losses were estimated by multiplying the price of the condemned part by the frequency of its occurrence owing to the disease. Similarly, indirect losses were estimated as the product of unit carcass price and reduction in carcass weight (CW) due to the disease. The direct impact on the beef cattle industry from MNL and ILI was estimated at around $1.29 million (US$1 = Y120) per year. A least-squares analysis showed that MNL had no influence on any carcass trait, whereas BFN and ILI significantly reduced CW, rib eye area and darkened the beef. ILI also reduced rib thickness. The indirect losses from BFN and ILI were estimated as a maximum of $131.7 and $256.4 per animal and around $6.26 million and $4.03 million for the industry, respectively, mostly because of the reduction in CW. PMID- 26277866 TI - The SFP research priority setting process. PMID- 26277865 TI - Significant association between functional microRNA polymorphisms and head and neck cancer susceptibility: a comprehensive meta-analysis. AB - Molecular epidemiological studies have showed a closer association between microRNA polymorphisms with and head and neck cancer (HNC) risk. But the results of these studies were inconsistent. We performed this meta-analysis to clarify the associations between microRNA polymorphisms and HNC risk. Four electronic databases (PubMed, Embase, CNKI, and Wanfang) were searched. Odds ratios (ORs) with 95% confidence interval (CIs) were calculated to assess the association between microRNA-146a rs2910164 G > C, microRNA-196a2 rs11614913 C > T, microRNA 149 rs2292832 C > T, microRNA-499 rs3746444 A > G polymorphisms and HNC risk. Heterogeneity, publication bias and sensitivity analysis were conducted to guarantee the statistical power. Overall, 11 selected articles involving 16100 subjects were included in this meta-analysis. Significantly increased risk between microRNA-146a rs2910164 G > C polymorphism and HNC risk were observed in Caucasian population (GC vs. GG: OR = 1.31, 95%CI = 1.01-1.68; GC + CC vs. GG: OR = 1.26, 95%CI = 1.02-1.57). For microRNA-196a2 rs11614913 C > T, similarly increased risk were also found in Asian population (T vs. C, OR = 1.14, 95%CI = 1.04-1.25; TT vs. CC, OR = 1.33, 95%CI = 1.09-1.61; CT + TT vs. CC OR = 1.32, 95%CI = 0.99-1.76; TT vs. CC + CT, OR = 1.14, 95%CI = 0.99-1.33). In addition, no significant association was detected between microRNA-149 rs2292832 C > T and microRNA-499 rs3746444 A > G polymorphism and HNC risk. This meta-analysis demonstrates that microRNA polymorphisms are associated with HNC development based on ethnicity diversity. PMID- 26277868 TI - Functional genetic variability at promoters of pro-(IL-18) and anti-(IL-10) inflammatory affects their mRNA expression and survival in prostate carcinoma patients: Five year follow-up study. AB - BACKGROUND: Inflammation is an important hallmark of all cancers. The net inflammatory response is determined by a delicate balance between pro- and anti inflammatory cytokines, which, in turn, is determined by the genetic make-up. The present study investigates the role of variations in the promoter regions of IL 18 and IL-10 (anti-inflammatory) cytokines on mRNA expressions and survival in prostate cancer (PCa) patients. METHODS: The study was conducted on 584 volunteer males (291 patients of PCa, between 40-80 years of age. Genetic variants were studied by using RFLP and confirmed by probe based method. Expressions of mRNA were evaluated by real-time PCR (Roche light cycler 480). Relative mRNA and fold change gene expressions were analyzed by ([1/2] (DeltaCt) ) and (2(-DeltaDeltaCt) ) methods, respectively, and 5 year follow-ups were evaluated by Log-rank (Mantel Cox) test with Log-rank test for trends. RESULTS: IL-18 mRNA expression was significantly elevated in GG genotypes (at -137) of PCa with relative mRNA expression of 13.95, that is, 8.48 folds higher (P < 0.05) than controls; and showed a significant median survival of 1243 days. The CC genotypes of IL-10 at both loci (-819 T/C and -592C/A) showed 3.63 and 3.52 higher relative mRNA expressions than controls, but poor survival of 984 and 1052 days than TT of 1359 days and AA of 1371 days. CONCLUSIONS: Genetic variants of pro-inflammatory IL-18 which showed higher relative mRNA expressions have better survival. Genetic variants of anti-inflammatory IL-10 with higher relative mRNA expression showed decreased chances of survival. PMID- 26277869 TI - Validation of a score to guide endometriosis therapy for the non-specialized gynecologist. AB - OBJECTIVE: To validate a tool-the ECO system-developed to guide non-specialized gynecologists in the treatment of patients with suspected endometriosis in outpatient clinics. METHODS: In a retrospective study, data were assessed from patients presenting to a center in Brazil or a center in Germany with suspected endometriosis and pelvic pain between July 2012 and June 2013. Data reviewed included patient complaints, clinical extent of disease, patient goals, recent use of medication, previous pelvic surgeries, visual analog pain scale, treatment provided, and histopathology after surgery. Data were transformed into a score according to the ECO system (0-6) indicating the suggested management, which was compared with the approach used in the study hospitals. RESULTS: Among 166 patients, 78 (47.0%) were medically treated and 88 (53.0%) underwent therapeutic laparoscopy. All 3 patients scoring 2 had undergone hormonal treatment. Among 51 patients scoring 3, 49 (96.1%) were clinically managed and 2 (3.9%) underwent surgery. Among 52 patients scoring 4, 26 (50.0%) had undergone medical treatment and 26 (50.0%) surgical treatment. All 56 patients who scored 5 and the four patients who scored 6 underwent surgery. CONCLUSION: The ECO system seems to effectively represent the management of patients with endometriosis in specialized services. PMID- 26277870 TI - Potential Clinical Use of Kisspeptin. AB - Over the last 10 years, kisspeptins--peptide products of varying lengths encoded by the KISS1 gene--have been found to be key regulators of normal reproductive function throughout life in animals and humans. By activating the kisspeptin receptor [previously known as orphan G protein-coupled receptor 54 (GPR54)], they elicit an effect on the central gonadotropin-releasing hormone neurons. Administration of kisspeptin by either the subcutaneous or intravenous route potently stimulates endogenous gonadotropin hormone release in healthy men and women as well as in animals. Kisspeptin also stimulates endogenous release of gonadotropins in subfertile as well as healthy volunteers, and therefore it has potential as a novel therapeutic agent in reproductive disorders. Further human studies have shown that chronic, high-dose administration of kisspeptin causes desensitisation with rapid subsequent suppression of the hypothalamic-pituitary gonadal axis, and therefore high-dose long-acting analogues may have a clinical role in treating sex hormone-dependent malignancies. By further elucidating the intricacies and mechanisms of the kisspeptin signalling system, and the tissues it acts on during different phases of the reproductive timeline (including during puberty, fertility, pregnancy and menopause), pharmacologic analogues could become clinically useful. PMID- 26277871 TI - Impaired Activity of Blood Coagulant Factor XIII in Patients with Necrotizing Enterocolitis. AB - Necrotizing enterocolitis (NEC) is the most common gastrointestinal (GI) medical/surgical emergency of the newborn and a leading cause of preterm neonate morbidity and mortality. NEC is a challenge to diagnose since it often shares similar clinical features with neonatal sepsis. In the present study, plasma protein profiling was compared among NEC, sepsis and control cohorts using gel electrophoresis, immunoblot and mass spectrometry. We observed significant impairment in the formation of fibrinogen-gamma dimers (FGG-dimer) in the plasma of newborns with NEC that could efficiently differentiate NEC and sepsis with a high level of sensitivity and specificity. Interestingly, the impaired FGG-dimer formation could be restored in NEC plasma by the addition of exogenous active factor XIII (FXIII). Enzymatic activity of FXIII was determined to be significantly lower in NEC subject plasma for crosslinking FGG when compared to sepsis. These findings demonstrate a potential novel biomarker and related biologic mechanism for diagnosing NEC, as well as suggest a possible therapeutic strategy. PMID- 26277872 TI - Effects of mild hypoalbuminemia on the pharmacokinetics and pharmacodynamics of dexmedetomidine in patients after major abdominal or thoracic surgery. AB - STUDY OBJECTIVE: To explore the effects of mild hypoalbuminemia on pharmacokinetics and pharmacodynamics of dexmedetomidine in patients after major abdominal or thoracic surgery. DESIGN: A prospective cohort study. SETTING: University-affiliated teaching hospital. PATIENTS: The study was performed in 30 consecutive patients undergoing major abdominal or thoracic surgery. They were aged 18 to 65 years and graded as American Society of Anesthesiologists physical status I and II. All patients were scheduled to require more than 6 hours of postoperative sedation and mechanical ventilation. Nine of the patients had low plasma albumin levels (<35 g/L but >24 g/L; male/female, 6/3) after the operation, who were assigned to hypoalbuminemia group, and the remainder with normoalbuminemia (>35 g/L; male/female, 15/6) were assigned to normoalbuminemia group. INTERVENTIONS: All patients were administered a loading dose of dexmedetomidine 1.0 MUg/kg infused over 10 minutes after admitted into intensive care unit and a maintenance dose of 0.4 MUg/kg per hour followed for 6 hours. MEASUREMENTS: Plasma dexmedetomidine levels were determined by high performance liquid chromatography - mass spectrum. Sedation was evaluated using Ramsay sedation score. Heart rate and arterial pressures were monitored. Adverse events were recorded. MAIN RESULTS: Compared with patients with normoalbuminemia, maximum plasma concentration of dexmedetomidine decreased by 21.2% in patients with hypoalbuminemia (P < .01). Its volume of distribution at steady state increased by 40.5%; elimination half-life decreased by 33.5% (P < .01). However, heart rates, arterial pressures, and Ramsay sedation scores did not differ significantly between the 2 groups. No serious adverse events occurred in either the patients with hypoalbuminemia or normoalbuminemia. CONCLUSIONS: Sedation and adverse reactions of dexmedetomidine infusion did not differ significantly between patients with mild hypoalbuminemia and normoalbuminemia, although its volume of distribution at steady state increased and elimination half-life shortened in patients with hypoalbuminemia. This suggests that dexmedetomidine infusion can safely be used in mild hypoalbuminemia patients after major abdominal or thoracic surgery. PMID- 26277873 TI - Local anesthetic injection deep to the fascia iliaca at the level of the inguinal ligament: the pattern of distribution and effects on the obturator nerve. AB - STUDY OBJECTIVE: The femoral, lateral femoral cutaneous, and obturator nerves (ONs) can reportedly be blocked using a single-injection deep to the fascia iliaca (FI) at the level of the inguinal ligament. Two commonly used methods (the FI compartment and 3-in-1 blocks) have produced inconsistent results with respect to local anesthetic distribution and effect on the ON. To date, no study of either method has been performed using advanced imaging techniques to document both needle placement and local anesthetic distribution. We report the outcome of a series of 3-in-1 and FI blocks performed using ultrasound to guide needle position and magnetic resonance imaging (MRI) to define local anesthetic distribution. DESIGN: Patients were prospectively studied, and images were interpreted using a randomized and blinded protocol. SETTING: The study was performed in the perioperative area of an academic orthopedic specialty hospital. PATIENTS: Ten patients (ASA 1-2) having anterior cruciate ligament reconstruction received either 3-in-1 or FI compartment blocks for postoperative analgesia using the surface landmarks described for these techniques. INTERVENTIONS: Ultrasound was used to position the injecting needle immediately deep to the FI. Local anesthetic distribution was studied using MRI. MEASUREMENTS: Patients were examined for motor and/or sensory function of the femoral, obturator, and lateral femoral cutaneous nerves. Magnetic resonance imaging was used to document the limits of injectate distribution. MAIN RESULTS: Magnetic resonance imaging showed distribution of injectate over the surface of the iliacus and psoas muscles to the level of the retroperitoneum. No patient showed medial extension of injectate to the ON. At the level of the inguinal ligament, injectate extended laterally toward the anterior superior iliac spine and medially to the femoral vein. All patients had significant weakness with extension of the knee and sensory loss over the anterior, lateral, and medial thigh. No patient demonstrated decreased hip adductor strength. CONCLUSIONS: Ultrasound and MRI show consistent superior extension of local anesthetic to the level of the retroperitoneum for both techniques. There was reliable clinical effect on the femoral and lateral femoral cutaneous nerves. However, none of the injections produced evidence of ON block either at the level of the retroperitoneum or the inguinal ligament. PMID- 26277874 TI - Health-related quality of life in children with heart failure as perceived by children and parents. AB - Advancements in paediatric heart failure management have resulted in improved survival and a focus on long-term outcomes including health-related quality of life. We compared health-related quality of life in children with heart failure with healthy patients, children with chronic conditions, and children with cardiovascular disease. Families (n=63) and children (n=73) aged 2-20 years with heart failure were enrolled and compared with data previously published for healthy patients (n=5480), those with chronic conditions (n=247), and those with cardiovascular disease (n=347). Patients and parents completed the PedsQL 4.0 and the Cardiac 3.0 Module health-related quality-of-life questionnaires. PedsQL scores including Total, Psychosocial Health Summary, and Physical were compared between groups. In general, patients with heart failure had lower scores than the healthy population (p=0.001), and comparable scores with those with chronic conditions. Parents perceived no difference in physical scores for children with heart failure when compared with healthy children, and perceived higher scores for children with heart failure when compared with those with chronic conditions (p?0.003). Furthermore, children with heart failure had decremental health related quality-of-life scores as the American Heart Association stage of heart failure increased, such that patients with stage C heart failure had scores similar to children with severe cardiovascular disease. Children with heart failure reported significantly impaired health-related quality of life compared with healthy children and similar scores compared with children with chronic conditions. Parental perceptions appear to underestimate these impairments. Children with heart failure appear to have progressive impairment of health related quality of life with advancing stage of heart failure. PMID- 26277875 TI - Delirium Tremens Leads to Poor Outcomes for Acute Coronary Syndrome. AB - OBJECTIVES: The mortality rate for patients with delirium tremens (DT) is 5%. As these patients present with elevated cardiac indices, coexisting DT in acute coronary syndrome (ACS) likely worsens outcomes. Our aim was to examine the outcomes of alcohol withdrawal syndrome (AWS) and DT in patients with ACS. METHODS: We used the Nationwide Inpatient Sample (2000-2009) for our study. A multivariable logistic regression model was used to examine the independent association of AWS on inhospital mortality and a multivariable linear regression was used to examine the effect of AWS on inpatient length of stay (LOS). RESULTS: An estimated 2,465,852 admissions with a primary diagnosis of ACS were analyzed. Of these, 4,499 patients had AWS and 3,460 patients had DT. Adjusting for age, gender, race, insurance, hospital characteristics, Charlson's comorbidity index, stent placement and year, the inhospital mortality was significant only for DT (OR 1.56; 95% CI 1.21-2.04). Inpatient LOS was 1.64 (95% CI 1.58-1.73) times higher in those with AWS and 2.33 (95% CI 2.22-2.43) times higher in DT when compared to nonalcoholics. Total hospital charges were higher for patients with AWS and DT when compared to nonalcoholics. CONCLUSIONS: Coexisting DT in ACS admissions is associated with increased mortality along with longer inpatient LOS and higher hospital costs. PMID- 26277876 TI - Longitudinal response of membrane thickness and ostium patency following sinus floor elevation: a prospective cohort study. AB - OBJECTIVES: To investigate the influence of sinus floor elevation (SFE) on sinus physiology, including Schneiderian membrane thickness (MT) and ostium patency, using cone beam computed tomography (CBCT). MATERIALS AND METHODS: Based on pre established selection criteria, 53 patients in combination with 53 sinuses were referred for SFE with a lateral approach using deproteinized bone mineral. CBCT was performed prior to, immediately after surgery and before staged implant placement. The Schneiderian MT of the elevated region, ostium patency, and other clinical data was evaluated. RESULTS: The two-stage sinus augmentation technique was applied in 33 males and 20 females. Four membrane perforations were observed during the surgical procedure. The Schneiderian membrane exhibited significant swelling immediately after augmentation (P < 0.0001), but this difference disappeared after a mean healing period of 7.51 months. The corresponding changes were also observed for ostium patency with a tendency of transient obstruction after surgery. Sinuses with flat mucosal thickening or pseudocysts did not present a liability of perforation compared to the normal cases, and the augmentation procedure was not likely to deteriorate the pathology of mucosal thickening or pseudocysts. CONCLUSIONS: The results show that SFE with a lateral approach has no significant influence on MT and ostium patency after the healing period except for postoperative transient swelling and obstruction. Thickened membranes and antral pseudocysts in a small size might not be contraindications to SFE from the standpoint of the surgical impact on the Schneiderian membrane. PMID- 26277877 TI - Can the optimal cervical length for placing ultrasound-indicated cerclage be identified? AB - OBJECTIVE: To assess a continuum of cervical length (CL) cut-offs for the efficacy of ultrasound-indicated cerclage in women with previous spontaneous preterm birth (PTB). METHODS: This was a planned secondary analysis of a multicenter randomized clinical trial of ultrasound-indicated cerclage for the prevention of PTB in high-risk women. The efficacy of cerclage for preventing recurrent PTB < 35, < 32 and < 24 weeks' gestation was assessed using multivariable logistic regression analysis. Odds ratios (ORs) and CIs were estimated for a range of CL cut-offs using bootstrap regression. The 2.5(th) and 97.5(th) percentiles of bootstrapped ORs determined the CIs. Results were illustrated using smoothed curves superimposed on estimated ORs by CL cut-off. RESULTS: Of 301 women with a CL < 25 mm, 142 underwent ultrasound-indicated cerclage and 159 did not have cerclage placement. The few cases with CL < 10 mm limited the evaluation to CL cut-offs between < 10 mm and < 25 mm. For PTB < 35 weeks, ORs in women with a cerclage and CL < 25 mm were statistically significantly lower than in those without cerclage, and efficacy was maintained at smaller CL cut-offs. Results were similar for PTB < 32 weeks. For PTB < 24 weeks, results differed, with ORs increasing toward unity (no benefit), with wide CIs, for CL cut-offs between < 10 mm and < 15 mm, attributed to the small number of births < 24 weeks. CONCLUSIONS: The efficacy of ultrasound-indicated cerclage in women with previous spontaneous PTB varies by action point CL cut-off and by PTB gestational age of interest. Cerclage significantly reduces the risk of PTB < 35 and < 32 weeks, at CL cut-offs between < 10 mm and < 25 mm, with the greatest reduction at shorter CL, affirming that women with prior spontaneous PTB and a short CL are appropriate candidates for ultrasound-indicated cerclage. Copyright (c) 2015 ISUOG. Published by John Wiley & Sons Ltd. PMID- 26277878 TI - Ultrasound assessment of congenital fetal lung masses and neonatal respiratory outcomes. AB - OBJECTIVE: Fetal congenital lung masses generate concern for compromised postnatal respiratory function. Congenital pulmonary adenomatoid malformation volume ratio (CVR) has been used to predict the risk of hydrops fetalis and need for antenatal intervention. This study investigates whether CVR could be used to predict neonatal respiratory outcomes. METHODS: The ultrasounds of fetuses diagnosed with a lung mass between 2005 and 2013 were reviewed. CVR was calculated at each ultrasound using the formula for a prolate ellipse divided by head circumference. The pregnancy outcome and information about NICU admission for respiratory insufficiency were collected. RESULTS: Forty-two fetuses were diagnosed with a lung mass during the study period. CVR prior to 24 weeks and between 24 and 32 weeks were associated with NICU admission (p < 0.0001 and <0.008, respectively). CVR increased up to 32 weeks and decreased thereafter for most subjects. The decrease in CVR beyond 32 weeks was larger for cases that required NICU admission (p = 0.002). For a CVR cut-off of <0.5, the sensitivity was 100%, the specificity 85.7%, and negative predictive value was 100% for regular nursery care. CONCLUSION: In pregnancies diagnosed with fetal lung masses, CVR predicted normal respiratory outcomes and need for NICU admission. This information may be helpful for delivery planning. (c) 2015 John Wiley & Sons, Ltd. PMID- 26277879 TI - Heart Rate Variability, Insulin Resistance, and Insulin Sensitivity in Japanese Adults: The Toon Health Study. AB - BACKGROUND: Although impaired cardiac autonomic function is associated with an increased risk of type 2 diabetes in Caucasians, evidence in Asian populations with a lower body mass index is limited. METHODS: Between 2009-2012, the Toon Health Study recruited 1899 individuals aged 30-79 years who were not taking medication for diabetes. A 75-g oral glucose tolerance test was used to diagnose type 2 diabetes, and fasting and 2-h-postload glucose and insulin concentrations were measured. We assessed the homeostasis model assessment index for insulin resistance (HOMA-IR) and Gutt's insulin sensitivity index (ISI). Pulse was recorded for 5 min, and time-domain heart rate variability (HRV) indices were calculated: the standard deviation of normal-to-normal intervals (SDNN) and the root mean square of successive difference (RMSSD). Power spectral analysis provided frequency domain measures of HRV: high frequency (HF) power, low frequency (LF) power, and the LF:HF ratio. RESULTS: Multivariate-adjusted logistic regression models showed decreased SDNN, RMSSD, and HF, and increased LF:HF ratio were associated significantly with increased HOMA-IR and decreased ISI. When stratified by overweight status, the association of RMSSD, HF, and LF:HF ratio with decreased ISI was also apparent in non-overweight individuals. The interaction between LF:HF ratio and decreased ISI in overweight individuals was significant, with the odds ratio for decreased ISI in the highest quartile of LF:HF ratio in non-overweight individuals being 2.09 (95% confidence interval, 1.41-3.10). CONCLUSIONS: Reduced HRV was associated with insulin resistance and lower insulin sensitivity. Decreased ISI was linked with parasympathetic dysfunction, primarily in non-overweight individuals. PMID- 26277880 TI - Tobacco Price Increase and Smoking Cessation in Japan, a Developed Country With Affordable Tobacco: A National Population-Based Observational Study. AB - BACKGROUND: Longitudinal assessment of the impact of tobacco price on smoking cessation is scarce. Our objective was to investigate the effect of a price increase in October 2010 on cessation rates according to gender, age, socioeconomic status, and level of tobacco dependence in Japan. METHODS: We used longitudinal data linkage of two nationally representative studies and followed 2702 smokers for assessment of their cessation status. The odds ratios (ORs) for cessation were calculated using logistic regression. To estimate the impact of the 2010 tobacco price increase on cessation, data from 2007 were used as a reference category. RESULTS: Overall cessation rates significantly increased from 2007 to 2010, from 3.7% to 10.7% for men and from 9.9% to 16.3% for women. Cessation rates were 9.3% for men who smoked 1-10 cigarettes per day, 2.7% for men who smoked 11-20 cigarettes per day, and 2.0% for men who smoked more than 20 cigarettes per day in 2007. These rates increased to 15.5%, 10.0%, and 8.0%, respectively, in 2010. The impact was stronger among subjects who smoked more than 11 cigarettes per day than those who smoked 1-10 cigarettes per day in both sexes: ORs for 2010 were 4.04 for those smoking 11-20 cigarettes per day, 4.26 for those smoking more than 20 cigarettes per day, and 1.80 for those smoking 1 10 cigarettes per day in the main model in men. There were no obvious differences in the relationship between tobacco price increase and smoking cessation across age and household expenditure groups. CONCLUSIONS: The tobacco price increase in Japan had a significant impact on smoking cessation in both sexes, especially among heavy smokers, with no clear difference in effect by socio-demographic status. PMID- 26277881 TI - Validity of a Self-Administered Food-Frequency Questionnaire for Assessing Amino Acid Intake in Japan: Comparison With Intake From 4-Day Weighed Dietary Records and Plasma Levels. AB - BACKGROUND: Interest in the physiological roles of amino acids and their impact on health outcomes is substantial and growing. This interest has prompted assessment of the habitual intake of amino acids for use in epidemiologic studies and in clarifying the association between habitual intake and plasma levels of amino acids. Here, we investigated the validity of ranking individuals according to dietary amino acid intake as estimated using a food frequency questionnaire (FFQ) in comparison with intakes from dietary records (DRs) and plasma levels. METHODS: A total of 139 men and women selected from examinees of the cancer screening program at the Research Center for Cancer Prevention and Screening, National Cancer Center, Japan, provided 4-day weighed DRs, a semi-quantitative FFQ, and plasma samples. Plasma levels of amino acids were measured using the UF Amino Station system. RESULTS: Spearman rank correlation coefficients of energy adjusted intake of amino acids from the DR and FFQ ranged from 0.40 to 0.65 for men and from 0.35 to 0.46 for women. Correlation coefficients of energy-adjusted intake from the DR and plasma levels ranged from -0.40 to 0.25 for men and from 0.16 to 0.11 for women. Similarly, no significant positive correlation coefficients were observed between intake from the FFQ and plasma levels for either men or women. CONCLUSIONS: We confirmed that this FFQ has moderate validity in estimating amino acid intake when 4-day weighed DRs are used as a reference method, suggesting that it is suitable for ranking individuals living in urban areas in Japan by amino acid intake. PMID- 26277882 TI - The triangle zone as a femoral attachment location in medial patellofemoral ligament reconstruction: An in vivo three-dimensional analysis using an open MRI scanner. AB - BACKGROUND: The exact isometric points for medial patellofemoral ligament (MPFL) fixation during MPFL reconstruction remain a matter of debate. PURPOSE: The aim of this study was to characterize the functional length changes of various patellar and femoral fixation sites using in vivo three-dimensional (3D) movement patterns and to determine the ideal fixation sites at which the graft remains largely isometric. METHODS: Twelve right knees of healthy volunteers were examined at early flexion angles (0 degrees , 10 degrees , 20 degrees , 30 degrees , 40 degrees , 50 degrees , and 60 degrees ) with a horizontal-type open magnetic resonance scanner, and 3D models were reconstructed using the marching cubes algorithm. Six points on the femoral condyle and three points on the medial aspect of the patella were simulated. The matching points represented the MPFL, which crossed the bony obstacle. The MPFL length changes were analyzed at various flexion degrees. RESULTS: The lengths from the dome of Blumensaat's line (G), the point 10mm inferior to the adductor tubercle (H), to the midpoint between the adductor tubercle and the medial epicondyle (I) were more isometric than other points. The lengths between the dome of Blumensaat's line and the superior pole of the patella changes significantly between 20 degrees and 60 degrees of flexion (p=0.040). CONCLUSIONS: The femoral fixation site may be more accurately located during MPFL reconstruction at the G, H, and I points to restore the native biomechanical function of the MPFL. The dome of Blumensaat's line should be avoided during MPFL reconstruction with the superficial quad technique. CLINICAL RELEVANCE: A triangular region composed of the dome of Blumensaat's line, 10mm inferior to the adductor tubercle, and the midpoint between the adductor tubercle and medial epicondyle is recommended as the femoral fixation site. PMID- 26277883 TI - Association of cortical thickness and neurological soft signs in patients with chronic schizophrenia and healthy controls. AB - BACKGROUND: Neurological soft signs (NSS), i.e. subtle neurological abnormalities, have been frequently found in schizophrenia. Neuroimaging studies in schizophrenia have shown abnormal cortical thickness changes across the cortical mantle. However, few studies have examined relationships between NSS and cortical thickness abnormalities in schizophrenia. METHOD: A sample of 18 patients with chronic schizophrenia and 20 age-matched healthy controls were included. Cortical thickness was assessed on high-resolution 3-tesla magnetic resonance imaging by using FreeSurfer software and NSS were rated on the Heidelberg Scale. RESULTS: Significant negative correlations between NSS and cortical thickness were found in the prefrontal, inferior temporal, superior parietal, postcentral, and supramarginal cortices in the schizophrenia patients. In the controls, however, this negative correlation was found in the anterior cingulate, pericalcarine and superior/middle temporal regions. CONCLUSION: Our results not only confirmed the association between NSS and cortical thickness in chronic schizophrenia but also indicated that patients and controls have different anatomical substrates of NSS. PMID- 26277884 TI - Cardiotoxin III Inhibits Hepatocyte Growth Factor-Induced Epithelial-Mesenchymal Transition and Suppresses Invasion of MDA-MB-231 Cells. AB - The epithelial-mesenchymal transition (EMT) is the first step required for breast cancer to initiate metastasis. In this study, hepatocyte growth factor (HGF) was used as a metastatic inducer of MDA-MB-231 cells. Cardiotoxin III (CTX III) inhibited HGF-induced morphological changes and upregulation of E-cadherin with the concomitant decrease in N-cadherin and Vimentin protein levels, resulting in inhibition of cell migration and invasion. CTX III-induced downregulation of transcription factors, Snail, Twist, and Slug, in MDA-MB-231 cells. CTX III suppressed c-Met phosphorylation and downstream activation of phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK)1/2. The c-Met specific inhibitor PHA665752 attenuated ERK1/2 and Akt phosphorylation, cell migration and invasion, as well as the expressional changes of EMT markers induced by HGF. Taken together, our data suggest that CTX III suppresses HGF/c-Met-induced cell migration and invasion by reversing EMT, which involves the inactivation of the HGF/c-Met-mediated ERK1/2 and PI3K/Akt pathways in MDA-MB-231 cells. PMID- 26277885 TI - Severe pulmonary hypertension associated with COPD: hemodynamic improvement with specific therapy. AB - BACKGROUND: There is no recommendation for treating pulmonary hypertension (PH) when associated with chronic obstructive pulmonary disease (COPD). OBJECTIVE: To evaluate the effect of PH-specific therapy in patients with COPD. METHODS: All successive patients with severe PH [mean pulmonary arterial pressure (mPAP) >=35 mm Hg] and COPD, who received specific PH medication and who underwent right heart catheterization at baseline and after 3-12 months of treatment, were analyzed from a prospective database. RESULTS: Twenty-six patients were included with a median follow-up of 14 months. Mean forced expiratory volume in 1 s was 57 +/- 20% of predicted, and mean forced expiratory volume in 1 s/forced vital capacity was 47 +/- 12%. Dyspnea was New York Health Association classification stage (NYHA) II in 15%, NYHA III in 81% and NYHA IV in 4%. First-line treatments were endothelin receptor antagonists in 11 patients, phosphodiesterase-5 inhibitors in 11 patients, calcium blocker in 1 patient, combination therapy in 3 patients including 2 with a prostanoid. After 6 +/- 3 months, pulmonary vascular resistance decreased from 8.5 +/- 3 to 6.6 +/- 2 Wood units (p < 0.001), with significant improvement of cardiac index from 2.44 +/- 0.43 to 2.68 +/- 0.63 liters * min * m-2 (p = 0.015) and mPAP from 48 +/- 9 to 42 +/- 10 mm Hg (p = 0.008). There was no significant difference in dyspnea, 6-min walking distance, echocardiographic parameters or N-terminal pro-brain natriuretic peptide levels. There was no significant difference in arterial oxygen saturation after 3-12 months of treatment. CONCLUSIONS: Specific PH medications may improve hemodynamic parameters in COPD patients with severe PH. Appropriate prospective randomized studies are needed to evaluate the potential long-term clinical benefit of treatment. PMID- 26277886 TI - Ultrashort Channel Length Black Phosphorus Field-Effect Transistors. AB - This paper reports high-performance top-gated black phosphorus (BP) field-effect transistors with channel lengths down to 20 nm fabricated using a facile angle evaporation process. By controlling the evaporation angle, the channel length of the transistors can be reproducibly controlled to be anywhere between 20 and 70 nm. The as-fabricated 20 nm top-gated BP transistors exhibit respectable on-state current (174 MUA/MUm) and transconductance (70 MUS/MUm) at a VDS of 0.1 V. Due to the use of two-dimensional BP as the channel material, the transistors exhibit relatively small short channel effects, preserving a decent on-off current ratio of 10(2) even at an extremely small channel length of 20 nm. Additionally, unlike the unencapsulated BP devices, which are known to be chemically unstable in ambient conditions, the top-gated BP transistors passivated by the Al2O3 gate dielectric layer remain stable without noticeable degradation in device performance after being stored in ambient conditions for more than 1 week. This work demonstrates the great promise of atomically thin BP for applications in ultimately scaled transistors. PMID- 26277888 TI - Localized Subcarinal Adenitis following Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration. AB - Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure for the diagnosis of mediastinal lymph nodes and masses. Its complications are rare and include hemorrhage, pneumothorax and infections such as mediastinitis. We report the case of a 51-year-old patient who presented with a localized subcarinal adenitis after EBUS-TBNA. Germs colonizing the oropharynx may have been dragged along by the echobronchoscope, inoculating the punctured mediastinal lymph node. PMID- 26277887 TI - Efficacy and safety of pioglitazone added to alogliptin in Japanese patients with type 2 diabetes mellitus: a multicentre, randomized, double-blind, parallel group, comparative study. AB - A phase IV, multicentre, randomized, double-blind, parallel-group, comparative study was conducted in Japanese subjects with type 2 diabetes mellitus (T2DM) who had inadequate glycaemic control, despite treatment with alogliptin in addition to diet and/or exercise therapy. Subjects with glycated haemoglobin (HbA1c) concentrations of 6.9-10.5% were randomized to receive 16 weeks' double-blind treatment with pioglitazone 15 mg, 30 mg once daily or placebo added to alogliptin 25 mg once daily. The primary endpoint was the change in HbA1c from baseline at the end of treatment period (week 16). Both pioglitazone 15 and 30 mg combination therapy resulted in a significantly greater reduction in HbA1c than alogliptin monotherapy [-0.80 and -0.90% vs 0.00% (the least squares mean using analysis of covariance model); p < 0.0001, respectively]. The overall incidence rates of treatment-emergent adverse events were similar among the treatment groups. Pioglitazone/alogliptin combination therapy was effective and generally well tolerated in Japanese subjects with T2DM and is considered to be useful in clinical settings. PMID- 26277889 TI - Impact of comorbidities and gender on the use of coronary interventions in patients with high-risk non-ST-segment elevation acute coronary syndrome. AB - OBJECTIVES: To determine the impact of gender and comorbidity on use of coronary interventions in patients diagnosed with high-risk non-ST-segment acute coronary syndrome (NSTEACS). BACKGROUND: Guidelines recommend the use of coronary angiography for all patients diagnosed with NSTEACS with high-risk features, except in the presence of severe comorbidities. However, little is understood about the relationship between gender, comorbidity, and the use of coronary interventions. METHODS: Retrospective analyses of the Victorian Admitted Episodes Data Set (VAED) including all patients diagnosed with NSTEACS with high-risk features on their first admission for ACS between June 2007 and July 2009. Hierarchical logistic regression models and correspondence analyses were used to understand the relationship between gender, comorbidities, and the use of coronary interventions. RESULTS: Out of 16,771 NSTEACS patients with high-risk features, 6,338 (38%) were female. Females were older than males (aged >=75: 62% vs 39%, p < 0.001) and more likely to have multiple comorbidities (>=2: 66% vs 59%, p < 0.001). After adjusting for potential confounders, females were more likely to receive no coronary intervention than males with a similar number of comorbid conditions (no comorbidities: OR 1.62, 95% CI 1.28-2.05; 1 comorbidity: OR 1.67, 95% CI 1.44-1.93; 2 comorbidities: OR 1.93, 95% CI 1.66-2.23; >=3 comorbidities: OR 1.42, 95% CI 1.27-1.60). CONCLUSIONS: Lower rates of coronary intervention in females persisted after adjusting for number of comorbidities which suggests that gender may bias decisions regarding referral for coronary intervention in high-risk NSTEACS independent of other factors. PMID- 26277891 TI - Microstructural characteristics of natural gas hydrates hosted in various sand sediments. AB - Natural gas hydrates have aroused worldwide interest due to their energy potential and possible impact on climate. The occurrence of natural gas hydrates hosted in the pores of sediments governs the seismic exploration, resource assessment, stability of deposits, and gas production from natural gas hydrate reserves. In order to investigate the microstructure of natural gas hydrates occurring in pores, natural gas hydrate-bearing sediments were visualized using microfocus X-ray computed tomography (CT). Various types of sands with different grain sizes and wettability were used to study the effect of porous materials on the occurrence of natural gas hydrates. Spatial distributions of methane gas, natural gas hydrates, water, and sands were directly identified. This work indicates that natural gas hydrates tend to reside mainly within pore spaces and do not come in contact with adjacent sands. Such an occurring model of natural gas hydrates is termed the floating model. Furthermore, natural gas hydrates were observed to nucleate at gas-water interfaces as lens-shaped clusters. Smaller sand grain sizes contribute to higher hydrate saturation. The wetting behavior of various sands had little effect on the occurrence of natural gas hydrates within pores. Additionally, geometric properties of the sediments were collected through CT image reconstructions. These findings will be instructive for understanding the microstructure of natural gas hydrates within major global reserves and for future resource utilization of natural gas hydrates. PMID- 26277890 TI - Patients' 'thingification', unexplained symptoms and response-ability in the clinical context: in response to 'Patients' substantialization of disease, the hybrid symptom and the metaphysical care', by Alexandra Parvan. AB - The types of diseases, or categories of suffering, referred to as medically unexplained symptoms or syndromes (MUS) are the focus for the following commentary. Such cases seem to invite reflection. The very nature of such complex patterns of disease and suffering raises a number of fundamental epistemological and ontological issues. Furthermore, such health challenges can serve as the basis for an exploration of how the suffering person as well as the medical caretaker comes to grip with disease, incapacitation or suffering. We have structured our comments into two parts: first, we will describe medically unexplained health problems as the background for an inquiry into a process wherein patients reify their suffering in order to meet their doctors on equal terms, which carries a potential for alienation. Second, we will reflect on Alexandra Parvan's text as regards patients' 'substantialization' of their disease, the resulting 'hybrid symptom' and a proposed model for care and healing. PMID- 26277892 TI - Ligation of CD180 inhibits IFN-alpha signaling in a Lyn-PI3K-BTK-dependent manner in B cells. AB - A hallmark of systemic lupus erythematosus (SLE) is the consistent production of various auto-antibodies by auto-reactive B cells. Interferon-alpha (IFN-alpha) signaling is highly activated in SLE B cells and plays a vital role in the antibody response by B cells. Previous studies have shown that CD180-negative B cells, which are dramatically increased in SLE patients, are responsible for the production of auto-antibodies. However, the association between CD180 and IFN alpha signaling remains unknown. In the present study, we explored the effect of CD180 on regulating the activation of IFN-alpha signaling in B cells. We found that the number of CD180-negative B cells was increased in MRL/Mp-Fas(lpr/lpr) lupus-prone mice compared with wild-type mice. Phenotypic analysis showed that CD180-negative B cells comprised CD138+ plasmablast/plasma cells and GL-7+ germinal center (GC) B cells. Notably, ligation of CD180 significantly inhibited the IFN-alpha-induced phosphorylation of signal transducer and activator of transcription 2 (STAT-2) and expression of IFN-stimulated genes (ISGs) in a Lyn PI3K-BTK-dependent manner in vitro. Moreover, ligation of CD180 could also inhibit IFN-alpha-induced ISG expression in B cells in vivo. Furthermore, the Toll-like receptor 7 and Toll-like receptor 9 signaling pathways could significantly downregulate CD180 expression and modulate the inhibitory effect of CD180 signaling on the activation of IFN-alpha signaling. Collectively, our results highlight the close association between the increased proportion of CD180 negative B cells and the activation of IFN-alpha signaling in SLE. Our data provide molecular insight into the mechanism of IFN-alpha signaling activation in SLE B cells and a potential therapeutic approach for SLE treatment. PMID- 26277893 TI - Long noncoding RNAs in innate immunity. AB - Long noncoding RNAs (lncRNAs) have been shown to play important roles in immune cell development and immune responses through different mechanisms, such as dosage compensation, imprinting, enhancer function, and transcriptional regulation. Although the functions of most lncRNAs are unclear, some lncRNAs have been found to control transcriptional or post-transcriptional regulation of the innate and adaptive immune responses via new methods of protein-protein interactions or pairing with DNA and RNA. Interestingly, increasing evidence has elucidated the importance of lncRNAs in the interaction between hosts and pathogens. In this review, an overview of the lncRNAs modes of action, as well as the important and diversified roles of lncRNAs in immunity, are provided, and an emerging paradigm of lncRNAs in regulating innate immune responses is highlighted. PMID- 26277894 TI - Retinoic acid enhances lactoferrin-induced IgA responses by increasing betaglycan expression. AB - Lactoferrin (LF) and retinoic acid (RA) are enriched in colostrum, milk, and mucosal tissues. We recently showed that LF-induced IgA class switching through binding to betaglycan (transforming growth factor-beta receptor III, TbetaRIII) and activation of canonical TGF-beta signaling. We investigated the combined effect of LF and RA on the overall IgA response. An increase in IgA production by LF was further augmented by RA. This combination effect was also evident in Ig germ-line alpha (GLalpha) transcription and GLalpha promoter activity, indicating that LF in cooperation with RA increased IgA isotype switching. We subsequently found that RA enhanced TbetaRIII expression and that this increase contributed to LF-stimulated IgA production. In addition to the IgA response, LF and RA in combination also enhanced the expression of the gut-homing molecules C-C chemokine receptor 9 (CCR9) and alpha4beta7 on B cells. Finally, peroral administration of LF and RA enhanced the frequency of CCR9+IgA+ plasma cells in the lamina propria. Taken together, these results suggest that LF in cooperation with RA can contribute to the establishment of gut IgA responses. PMID- 26277895 TI - How regulatory T cells sense and adapt to inflammation. PMID- 26277897 TI - The IL-33/ST2 axis is specifically required for development of adipose tissue resident regulatory T cells. PMID- 26277896 TI - Extracellular calcium elicits feedforward regulation of the Toll-like receptor triggered innate immune response. AB - Despite the expanding knowledge on feedback regulation of Toll-like receptor (TLR) signaling, the feedforward regulation of TLR signaling for the proper innate response to invading microbes is not fully understood. Here, we report that extracellular calcium can coordinate the activation of the small GTPases Ras and Ras-proximate-1 (Rap1) upon TLR stimulation which favors activation of macrophages through a feedforward mechanism. We show that different doses of TLR agonists can trigger different levels of cytokine production, which can be potentiated by extracellular calcium but are impaired by the chelating reagent ethylene glycol tetraacetic acid (EGTA) or by knockdown of stromal interaction molecule 1 (STIM1). Upon TLR engagement, GTP-bound Ras levels are increased and GTP-bound Rap1 is decreased, which can be reversed by EGTA-mediated removal of extracellular calcium. Furthermore, we demonstrate that Rap1 knockdown rescues the inhibitory effects of EGTA on the TLR-triggered innate response. Examination of the TLR signaling pathway reveals that extracellular calcium may regulate the TLR response via feedforward activation of the extracellular signal-regulated kinase signaling pathway. Our data suggest that an influx of extracellular calcium, mediated by STIM1-operated calcium channels, may transmit the information about the intensity of extracellular TLR stimuli to initiate innate responses at an appropriate level. Our study may provide mechanistic insight into the feedforward regulation of the TLR-triggered innate immune response. PMID- 26277898 TI - The breast tumor microenvironment alters the phenotype and function of natural killer cells. AB - Natural killer (NK) cells are innate immune cells with the ability to identify and eliminate transformed cells. However, within tumors, many studies have described NK cells as non-functional. The developmental stage of tumor-associated NK cells and how this may relate to functionality has not been explored. We examined the developmental state of NK cells from polyoma middle T antigen (pyMT) transgenic mouse (MMTV-pMT) breast tumors. In pyMT tumors, NK cells were immature as evidenced by their decreased expression of DX5 and their CD27(low)CD11b(low) phenotype. These immature NK cells also had increased expression of NKG2A and expressed low levels of NKp46, perforin, and granzyme B. In contrast, splenic NK cells isolated from the same mice maintained their maturity and their expression of activation markers. To delineate whether the tumor microenvironment directly alters NK cells, we adoptively transferred labeled NK cells and followed their activation status in both the spleen and the tumor. NK cells that arrived at the tumor had half the expression of NKp46 within three days of transfer in comparison to those which arrived at the spleen. In an effort to modify the tumor microenvironment and assess the plasticity of intratumoral NK cells, we treated pyMT tumors with IL-12 and anti-TGF-beta. After one week of treatment, the maturity of tumor-associated NK cells was increased; thus, indicating that these cells possess the ability to mature and become activated. A better understanding of how NK cells are modified by the tumor microenvironment will help to develop strategies aimed at bolstering immune responses against tumors. PMID- 26277899 TI - Preferential loss of gut-homing alpha4beta7 CD4+ T cells and their circulating functional subsets in acute HIV-1 infection. AB - Preferential infection and depletion of gut-homing alpha4beta7 CD4+ T cells in the blood are observed in chronic HIV/SIV infection. The dynamic change in gut homing alpha4beta7 CD4+ T cells and their functional subsets during the acute stages of HIV-1 infection are less documented. Therefore, we conducted a cohort study to investigate whether acute HIV-1 infection induced abnormalities in gut homing alpha4beta7 CD4+ T cells and their functional subsets. We examined the frequency, absolute number, and functionality of gut-homing alpha4beta7 CD4+ T cells in 26 acute HIV-1-infected patients compared with 20 healthy individuals. We found that circulating gut-homing alpha4beta7 CD4+ T cells were preferentially depleted during acute HIV-1 infection and were positively correlated with absolute CD4+ T-cell count in blood. Notably, Th17 and Th1 cell subsets of gut homing CD4+ T cells were also decreased, which resulted in an imbalance of T helper cells (Th1):regulatory T cells (Treg) and Treg:Th17 ratios. Gut-homing Th17 and Th1 cells were also positively correlated with the absolute number of total CD4+ T cells and gut-homing CD4+ T cells. The gut-homing Treg:Th17 ratio was inversely correlated with the CD4+ T-cell count. Taken together, the analyses of our acute HIV-1 cohort demonstrate that gut-homing alpha4beta7 CD4+ T cells and their functional subsets were profoundly depleted during acute HIV-1 infection, which may have resulted in the persistent loss of circulating CD4+ T cells and an imbalance of Th1:Treg and Treg:Th17 ratios and contribute to HIV-1 disease pathogenesis. PMID- 26277901 TI - Thermal-induced force release in oxyhemoglobin. AB - Oxygen is released to living tissues via conformational changes of hemoglobin from R-state (oxyhemoglobin) to T-state (desoxyhemoglobin). The detailed mechanism of this process is not yet fully understood. We have carried out micromechanical experiments on oxyhemoglobin crystals to determine the behavior of the Young's modulus and the internal friction for temperatures between 20 degrees C and 70 degrees C. We have found that around 49 degrees C oxyhemoglobin crystal samples undergo a sudden and strong increase of their Young's modulus, accompanied by a sudden decrease of the internal friction. This sudden mechanical change (and the ensuing force release) takes place in a partially unfolded state and precedes the full denaturation transition at higher temperatures. After this transformation, the hemoglobin crystals have the same mechanical properties as their initial state at room temperatures. We conjecture that it can be relevant for explaining the oxygen-releasing function of native oxyhemoglobin when the temperature is increased, e.g. due to active sport. The effect is specific for the quaternary structure of hemoglobin, and is absent for myoglobin with only one peptide sequence. PMID- 26277900 TI - Human dNK cell function is differentially regulated by extrinsic cellular engagement and intrinsic activating receptors in first and second trimester pregnancy. AB - Decidual natural killer (dNK) cells express an array of activation receptors to regulate placental immunity and development during early pregnancy. We investigated the functional character of human dNK cells during the first and second trimester of gestation and the interaction between dNK and trophoblast cells. Although the frequency of CD56+CD16- dNK among the total CD45+ leukocytes did not change over this period, the expression of the activating receptors, NKp80 and NKG2D, was greatly upregulated. We observed a significantly higher number of extravillous trophoblast cells in proximity to the dNK cells in the first trimester in comparison with the second trimester decidua. NKG2D expression by first trimester dNK cells was decreased when co-cultured with the HTR-8 trophoblast cell line. In the second trimester, functional markers of dNK activation, i.e., angiogenic factor production (e.g., vascular endothelial growth factor, interleukin-8, interferon-gamma), remained stable despite an increase in NKp80 or NKG2D surface expression. Furthermore, the degranulation capacity of dNK cells, as assessed by CD107a, was decreased in the second trimester. We suggest that in the first trimester, trophoblast-dNK interactions generate a population of dNK cells with a suppressed activating phenotype. In the second trimester, the loss of trophoblast-dNK interactions led to the inhibition of dNK cell function, although their activating receptor expression was increased. We speculate that during pregnancy, two mechanisms operate to modulate the dNK cell activation:suppression of activating receptor levels in the first trimester by trophoblasts and disengagement of receptor-ligand coupling in the second trimester. PMID- 26277902 TI - High-Dose Benzodiazepine Use among Long-Term Users: When Will We Ever Learn? PMID- 26277903 TI - Improving the accuracy of the k-shell method by removing redundant links: From a perspective of spreading dynamics. AB - Recent study shows that the accuracy of the k-shell method in determining node coreness in a spreading process is largely impacted due to the existence of core like group, which has a large k-shell index but a low spreading efficiency. Based on the analysis of the structure of core-like groups in real-world networks, we discover that nodes in the core-like group are mutually densely connected with very few out-leaving links from the group. By defining a measure of diffusion importance for each edge based on the number of out-leaving links of its both ends, we are able to identify redundant links in the spreading process, which have a relatively low diffusion importance but lead to form the locally densely connected core-like group. After filtering out the redundant links and applying the k-shell method to the residual network, we obtain a renewed coreness ks for each node which is a more accurate index to indicate its location importance and spreading influence in the original network. Moreover, we find that the performance of the ranking algorithms based on the renewed coreness are also greatly enhanced. Our findings help to more accurately decompose the network core structure and identify influential nodes in spreading processes. PMID- 26277904 TI - Health-Related Quality of Life in Children with Congenital Adrenal Hyperplasia. AB - BACKGROUND/AIMS: Factors in congenital adrenal hyperplasia (CAH) that may affect quality of life (QOL) include the need for lifelong medication, the risk of adrenal crisis, and hyperandrogenic symptoms. The objectives were to evaluate health-related QOL (HRQOL) in children with CAH, and whether CAH poses an additional burden compared to other endocrine disorders. METHODS: The validated PedsQL 4.0 generic core scales were administered to subjects (8-18 years) with CAH and hypothyroidism and their parents. The minimal clinically important difference (MCID) was determined for each scale score, allowing a comparison with the healthy population. A score of >1 standard deviation below the population mean was considered at risk for impaired HRQOL. RESULTS: In CAH, the mean total HRQOL scores were >1 MCID below the population mean, and a higher percentage than expected had scores considered at risk. CONCLUSION: Compared to subjects with hypothyroidism, subjects with CAH self-reported lower school domain scores. CAH subjects more frequently reported peers not wanting to be friends. PMID- 26277905 TI - Predictors of consistent condom use among Portuguese women attending family planning clinics. AB - Women account for 30% of all AIDS cases reported to the Health Ministry in Portugal and most infections are acquired through unprotected heterosexual sex with infected partners. This study analyzed socio-demographic and psychosocial predictors of consistent condom use and the role of education as a moderator variable among Portuguese women attending family planning clinics. A cross sectional study using interviewer-administered fully structured questionnaires was conducted among 767 sexually active women (ages 18-65). Logistic regression analyses were used to explore the association between consistent condom use and the predictor variables. Overall, 78.7% of the women were inconsistent condom users. The results showed that consistent condom use was predicted by marital status (being not married), having greater perceptions of condom negotiation self efficacy, having preparatory safer sexual behaviors, and not using condoms only when practicing abstinence. Living with a partner and having lack of risk perception significantly predicted inconsistent condom use. Less educated women were less likely to use condoms even when they perceive being at risk. The full model explained 53% of the variance in consistent condom use. This study emphasizes the need for implementing effective prevention interventions in this population showing the importance of taking education into consideration. PMID- 26277906 TI - Using Administrative Mental Health Indicators in Heart Failure Outcomes Research: Comparison of Clinical Records and International Classification of Disease Coding. AB - BACKGROUND: Use of mental indication in health outcomes research is of growing interest to researchers. This study, as part of a larger research program, quantified agreement between administrative International Classification of Disease (ICD-9) coding for, and "gold standard" clinician documentation of, mental health issues (MHIs) in hospitalized heart failure (HF) patients to determine the validity of mental health administrative data for use in HF outcomes research. METHODS: A 13% random sample (n = 504) was selected from all unique patients (n = 3,769) hospitalized with a primary HF diagnosis at 4 San Diego County community hospitals during 2009-2012. MHI was defined as ICD-9 discharge diagnostic coding 290-319. Records were audited for clinician documentation of MHI. RESULTS: A total of 43% (n = 216) had mental health clinician documentation; 33% (n = 164) had ICD-9 coding for MHI. ICD-9 code bundle 290-319 had 0.70 sensitivity, 0.97 specificity, and kappa 0.69 (95% confidence interval 0.61-0.79). More specific ICD-9 MHI code bundles had kappas ranging from 0.44 to 0.82 and sensitivities ranging from 42% to 82%. CONCLUSIONS: Agreement between ICD-9 coding and clinician documentation for a broadly defined MHI is substantial, and can validly "rule in" MHI for hospitalized patients with heart failure. More specific MHI code bundles had fair to almost perfect agreement, with a wide range of sensitivities for identifying patients with an MHI. PMID- 26277907 TI - Prognostic Value of Serial Measurements of Soluble Suppression of Tumorigenicity 2 and Galectin-3 in Ambulatory Patients With Chronic Heart Failure. AB - BACKGROUND: B-Type natriuretic peptides (BNP) and cardiac troponin T (cTnT) predict cardiovascular events in heart failure (HF) patients, but additional refinement in risk stratification may be possible by targeting pathways leading to fibrosis. We aimed to assess the value of serial measurements of soluble suppression of tumorigenicity 2 (sST2) and galectin-3 to identify risk for adverse pathophysiologic processes. METHODS: New York Heart Association (NYHA) functional class III-IV HF patients (n = 180; LVEF <=40%) were prospectively evaluated with biomarkers collected every 3 months over 2 years and analyzed regarding a primary end point of death/cardiac transplantation and a secondary end point of HF-related hospitalization or death/transplantation. RESULTS: Time dependent univariate analyses demonstrated that elevations of sST2 (>=49.3 ng/mL male, >=33.5 ng/mL female) and galectin-3 (>=22.1 ng/mL) were predictive of the primary and secondary end points. In multivariate models adjusted for BNP, cTnT, and clinical variables, sST2 but not galectin-3 remained an independent predictor (hazard ratio 3.22, 95% confidence interval 1.76-5.89; P < .001). With serial measurements, only sST2 demonstrated incremental value in reclassifying patients to higher risk. CONCLUSIONS: Serial monitoring of sST2 (indicating myocardial fibrosis and remodeling) and cTnT (reflecting myocardial injury) identifies highest-risk HF outpatients and may be valuable to guide patient tailored therapy during follow-up evaluations. Serial galectin-3 monitoring in ambulatory HF patients may not be of benefit. PMID- 26277908 TI - Synthetic biology and biomimetic chemistry as converging technologies fostering a new generation of smart biosensors. AB - Biosensors are powerful tunable systems able to switch between an ON/OFF status in response to an external stimulus. This extraordinary property could be engineered by adopting synthetic biology or biomimetic chemistry to obtain tailor made biosensors having the desired requirements of robustness, sensitivity and detection range. Recent advances in both disciplines, in fact, allow to re-design the configuration of the sensing elements - either by modifying toggle switches and gene networks, or by producing synthetic entities mimicking key properties of natural molecules. The present review considered the role of synthetic biology in sustaining biosensor technology, reporting examples from the literature and reflecting on the features that make it a useful tool for designing and constructing engineered biological systems for sensing application. Besides, a section dedicated to bioinspired synthetic molecules as powerful tools to enhance biosensor potential is reported, and treated as an extension of the concept of biomimetic chemistry, where organic synthesis is used to generate artificial molecules that mimic natural molecules. Thus, the design of synthetic molecules, such as aptamers, biomimetics, molecular imprinting polymers, peptide nucleic acids, and ribozymes were encompassed as "products" of biomimetic chemistry. PMID- 26277909 TI - Pneumoperitoneum, a urological source. PMID- 26277910 TI - Development of an overlapping PCR method to clone the full genome of infectious hypodermal and hematopoietic necrosis virus (IHHNV). AB - Decapod Penstyldensovirus 1, previously named as infectious hypodermal and hematopoietic necrosis virus (IHHNV), is an economically important pathogen that causes shrimp diseases worldwide. However, a rapid method for cloning full-length IHHNV genome sequences is still lacking, which makes it difficult to study the genomics and molecular epidemiology of IHHNV. Here, a novel and rapid PCR technique was developed to determine the complete genomic sequences of IHHNV. The IHHNV genome was amplified in two overlapping fragments which each yielded a 2kb PCR product covering the first half or the second half of IHHNV genome, respectively. Using this method, six complete genomic sequences of IHHNV, which were collected from different regions of Zhejiang province in China, were cloned and sequenced successfully. The new cloning method will greatly facilitate the study on the genomics and molecular epidemiology of IHHNV. PMID- 26277911 TI - Comparison of the AdvanSureTM real-time RT-PCR and Seeplex((r)) RV12 ACE assay for the detection of respiratory viruses. AB - The AdvanSureTM RV real-time PCR kit (AdvanSure; LG Life Sciences, Korea) is based on multiplex real-time PCR and can simultaneously detect 14 respiratory viruses. We compared the performance of the AdvanSure assay with the Seeplex RV 12 ACE detection kit (Seeplex; Seegene, Seoul, South Korea), a multiplex end point PCR assay. A total of 454 consecutive respiratory specimens were tested with both AdvanSure and Seeplex assays; AdvanSure detected 153 (33.7%) positive cases and Seeplex detected 145 (31.9%) positive cases. The positive percent agreement, negative percent agreement, and kappa value for the two assays were 87.2% (95% CI, 80.3-92.1), 91.1% (95% CI, 87.2-93.9), and 0.77 (95% CI, 0.70 0.83), respectively. Compared with the Seeplex assay, the AdvanSure assay had a shorter turnaround time (3h vs. 8h) and a shorter hands-on time (<1h vs 2h). In conclusion, the AdvanSure assay demonstrated comparable performance to the Seeplex assay. PMID- 26277912 TI - Copper(I)-Catalyzed Radical Addition of Acetophenones to Alkynes in Furan Synthesis. AB - A synthesis of multisubstituted furans from readily available acetophenones and electron-deficient alkynes via direct C(sp(3))-H bond functionalization under radical reaction conditions is described. The developed transformation is catalyzed by copper(I) salts using di-tert-butyl peroxide as an external oxidant. This method offers an efficient access to biologically important scaffolds from simple compounds. PMID- 26277913 TI - Mechanistic elucidation of C-H oxidation by electron rich non-heme iron(IV)-oxo at room temperature. AB - Non-heme iron(IV)-oxo species form iron(III) intermediates during hydrogen atom abstraction (HAA) from the C-H bond. While synthesizing a room temperature stable, electron rich, non-heme iron(IV)-oxo compound, we obtained iron(III) hydroxide, iron(III)-alkoxide and hydroxylated-substrate-bound iron(II) as the detectable intermediates. The present study revealed that a radical rebound pathway was operative for benzylic C-H oxidation of ethylbenzene and cumene. A dissociative pathway for cyclohexane oxidation was established based on UV-vis and radical trap experiments. Interestingly, experimental evidence including O-18 labeling and mechanistic study suggested an electron transfer mechanism to be operative during C-H oxidation of alcohols (e.g. benzyl alcohol and cyclobutanol). The present report, therefore, unveils non-heme iron(IV)-oxo promoted substrate-dependent C-H oxidation pathways which are of synthetic as well as biological significance. PMID- 26277914 TI - Association of TGFB1 -509C/T polymorphism gene with clinical variability in cystic fibrosis patients: A case-control study. AB - PURPOSE: In this work, we are interested to study the implication of -509C/T polymorphism, located in the promoter region of TGFB1 (transforming growth factor beta1), in the phenotypic variability of CF patients. PATIENTS AND METHODS: The present study enrolled 111 CF patients and 100 healthy control subjects. The study of the -509C/T polymorphism was performed using PCR-RFLP method. RESULTS: We found that patients carried non-F508del homozygous mutation with TT genotype was associated to lung symptoms (P=0.04). This association was not found in the sub-groups of patients with F508del at homozygous state P=0.145. No association was found between this polymorphism and the variability of digestive, pancreatic and ileus meconial symptoms. CONCLUSION: On the basis of our results, the -509C/T polymorphism of the TGFB1 gene seems to be a modulator factor of cystic fibrosis. PMID- 26277915 TI - CXCL12 and CXCR4 as predictive biomarkers of glioma recurrence pattern after total resection. AB - PURPOSE OF THE STUDY: Previous studies have shown that the pattern of recurrence for glioma is related to the direction of glioma cell invasion. Recent studies demonstrated that the CXCL12/CXCR4 signaling pathway mediates cellular invasion in glioma. Therefore, in this study, we investigated the possible relationship between CXCL12/CXCR4 expression and recurrence pattern in glioma. PATIENTS AND METHODS: Immunohistochemical techniques were used to assess CXCL12/CXCR4 expression in 42 glioma tissues following total resection. According to magnetic resonance imaging (MRI) of gliomas, the recurrence pattern was classified as close or distant pattern. The relationship between recurrence pattern and CXCL12/CXCR4 expression were initially examined by Chi-squared analysis. The prognostic significance of CXCL12 and CXCR4 was determined by log-rank tests and COX proportional hazards model. RESULTS: CXCL12 was expressed mainly in vascular endothelial cells and CXCR4 was expressed mainly in tumor cells. The recurrence pattern was significantly related to the expression level of CXCL12 in vascular endothelial cells (P=0.002) and CXCR4 in tumor cells (P=0.004). However, CXCL12 and CXCR4 were not independent prognostic factors for progression-free survival or overall survival in glioma patients. CONCLUSION: The glioma recurrence pattern is related to CXCL12 expression levels in vascular endothelial cells and CXCR4 expression levels in tumor cells; thus, implicating the CXCL12/CXCR4 signaling pathway as a potential target for glioma therapy. PMID- 26277916 TI - Rare case of cutaneous involvement of Lennert lymphoma as an initial manifestation. PMID- 26277917 TI - Metabolic syndrome, insulin resistance, and mammographic density in pre- and postmenopausal women. AB - Little is known about the association of metabolic syndrome (MetS) or insulin resistance (IR) with mammographic density, a strong risk factor for breast cancer. The goal of this study was to evaluate these associations in pre- and postmenopausal women. A cross-sectional study was performed in 73,974 adult women who underwent a comprehensive health screening examination that included a mammogram between 2011 and 2013 (mean age 42.6 years). MetS was defined according to the modified National Cholesterol Education Program Adult Treatment Panel III. IR was assessed with the homeostasis model assessment-insulin resistance (HOMA IR). Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for dense breast were estimated using logistic regression models after adjustment for potential confounders. In premenopausal women, MetS and all its components except waist circumference were associated with dense breast. After adjustment for potential confounders, the OR (95% CI) for dense breast in women with MetS compared with those without MetS was 1.22 (1.06-1.39). In postmenopausal women, however, there was positive but non-significant association between MetS and dense breast. In both pre- and postmenopausal women, high blood glucose and IR were positively associated with dense breast. The OR (95% CI) for dense breast between the highest and lowest quartiles of HOMA-IR was 1.29 (1.20-1.39) for premenopausal women and 1.44 (1.05-1.97) for postmenopausal women. In a large sample of Korean women, MetS and IR were associated with mammographic dense breast, demonstrating that IR, a potentially modifiable risk factor, may increase breast cancer risk, possibly through high mammographic density. PMID- 26277919 TI - Cystoidosoma hermaphroditus sp. n., the first representative of the quill mite family Ascouracaridae (Acari: Astigmata: Pterolichoidea) from an owl (Aves: Strigiformes). AB - The mite family Ascouracaridae Gaud et Atyeo, 1976 contains large-sized mites (mostly > 1 mm) which live inside the quills of birds of several orders. To date, no representative of this family has been found associated with the order Strigiformes (owls). In this paper, a new species of this family, Cystoidosoma hermaphroditus sp. n., is described from the tropical screech owl, Megascops choliba (Vieillot) (Aves: Strigiformes) from Brazil. This species is unique in having an external spermaduct, a primary duct and a rudimentary bursa copulatrix present in males. This is the first astigmatan feather mite described from the order Strigiformes in this country. A key to adults of the genus Cystoidosoma Gaud et Atyeo, 1976 of the world is presented. PMID- 26277918 TI - Multiple Comorbidities and Interest in Research Participation Among Clients of a Nonprofit Food Distribution Site. AB - BACKGROUND: Persons accessing food from nonprofit distribution sites face numerous challenges and typically have significant unmet health needs. However, given limited and intermittent healthcare system engagement, this vulnerable population is underrepresented in clinical research. We sought to better understand the health needs of a nonclinical population to inform future research and interventions. METHODS: Focus groups were conducted in English (n = 4) and Spanish (n = 4) with clients of Crossroads Community Services (CCS), the largest distributor of North Texas Food Bank. Discussions probed participants' health status, healthcare utilization, understanding and utilization of mammography, and attitudes toward participation in research. RESULTS: Participants included 42 CCS clients, primarily Hispanic or African American women. Participants reported multiple comorbid conditions among household members, yet utilization of health services was often limited by cost. The majority expressed interest in participating in research to communicate their health concerns and obtain emotional support. CONCLUSION: CCS clients represent a high-need, under-reached population willing to engage in health-related research that affords them opportunity to connect with peers in group settings and obtain information to improve management of daily life challenges. The Community Assistance Research (CARe) Initiative, a community-academic collaboration, establishes a much-needed opportunity for ongoing clinical research and intervention among this underserved population. PMID- 26277921 TI - Examining the preventable but predictable death of Ashley Smith. AB - PURPOSE: The purpose of this paper is to examine the fusion of psy-correctional discourse with the dominant risk logic to consider the implication this nexus can have on how self-injurious behaviour committed by women in prison is interpreted and responded to by the Correctional Service Canada (CSC). DESIGN/METHODOLOGY/APPROACH: The central focus of the study is an in-depth case analysis of the carceral death of Ashley Smith, a 19-year-old woman who committed suicide in her segregation cell in 2007 after enduring four years of excessively punitive treatment aimed at controlling her self-injurious behaviour. FINDINGS: Findings illustrate how the fusion of these logics creates a kind of "therapeutic risk cloak" that reframes the behaviour as "abnormal" and "risky", which masks the punitivity of strip search and segregation interventions in the name of safety, security and treatment. ORIGINALITY/VALUE: Given that correctional officials knowingly failed to intervene when Smith tied the fatal ligature around her neck, a federal inquiry judged her death to be a homicide. By attempting to unveil the "therapeutic-risk cloak" the authors hope to challenge the underlying logic of CSC's governance and management framework, which not only denies the oppressive gendered carceral reality that is linked to self-injurious behaviour amongst women prisoners, but is also used to justify intervention responses that exacerbate the very behaviour this framework aims to control. Until systemic transformation is achieved that eradicates CSC's contradictory governance framework, there is no doubt that the authors will continue to see similar preventable deaths take place in prison. PMID- 26277920 TI - The effects of patient education programs on medication use among asthma and COPD patients: a propensity score matching with a difference-in-difference regression approach. AB - BACKGROUND: Adherence to medication is one of the critical determinants of successful management of chronic diseases including asthma and chronic obstructive pulmonary disease (COPD). Given that poor adherence with self management medication is very common among asthma and COPD patients, interventions that improve the use of chronic disease management medications for this patient group have potential to generate positive health outcomes. In an effort to improve asthma and COPD care, the Lung Association of Saskatchewan has implemented an intervention by providing access to effective and high quality asthma and COPD education for both patients and health care professionals along with increasing access to spirometry. By evaluating the impacts of this intervention, our purpose in this paper is to examine the effectiveness of spirometry use, and asthma and COPD education in primary care setting on medication use among asthma and COPD patients. METHODS: At the time of the intervention, the Lung Association of Saskatchewan has not assigned a control group. Therefore we used a propensity score matching to create a control group using administrative health databases spanning 6 years prior to the intervention. Using Saskatchewan administrative health databases, the impacts of the intervention on use of asthma and COPD medications were estimated for one to four years after the intervention using a difference in difference regression approach. RESULTS: The paper shows that overall medication use for the intervention group is higher than that of the control group. On average, intervention group uses more asthma and COPD drugs. Within the asthma and COPD drugs, this intervention creates a persistent effect over time in the form of higher utilization of chronic management drugs equivalent to $157 and $195 in a given year during four years after the intervention. CONCLUSIONS: The study suggests that effective patient education and increasing access to spirometry increases the utilization of chronic disease management drugs among asthma and COPD patients. This type of interventions with patient education focus has potential to save healthcare dollars by providing better disease management among this patient group. PMID- 26277922 TI - Psychotherapy and despair in the prison setting. AB - PURPOSE: The purpose of this paper is to outline research which aimed to explore psychotherapists' experience of working with despair, in the UK prison setting, through a qualitative phenomenological approach. Within the forensic psychological literature, despair is considered a pathology, associated with suicide and self-harm, resulting from the prisoners histories and the coercive prison setting. In turn, therapeutic writings outline the importance of therapy in the prison setting with despair in providing coping skills, containment and learning opportunities for the prisoners involved. DESIGN/METHODOLOGY/APPROACH: Within the study, ten psychotherapists were interviewed as to their experience of working with clients in despair in the prison setting. The data were analysed via the phenomenological research method Empirical Phenomenological Analysis (EPA), and a secondary analysis through reverie. FINDINGS: Through the analysis by EPA, despair emerged in the prison setting as a destabilising phenomenon to which there was no protocol for working with it. Participants also described the prisoners' despair and the despairing prison setting, touching on their own sense of vulnerability and despair. However, drawing on the secondary analysis by reverie, the researcher also became aware of how the phenomenon of despair emerged not simply through the said, but also through the intersubjective. ORIGINALITY/VALUE: It was therefore through the secondary analysis by reverie that the importance of the attendance to aspects of intersubjectivity in prison research emerged. This paper contributes to the therapeutic writings on despair in the prison setting, alongside holding implications for qualitative research in the prison setting. PMID- 26277923 TI - Learning from peer support schemes--can prison listeners support offenders who self-injure in custody? AB - PURPOSE: The purpose of this paper is to critically evaluate the current evidence for peer support in prisons, in particular its contribution to working with prisoners who self-injure and the extent to which the success of peer support schemes such as the prison listeners, hinges upon staff's willingness to engage with the initiative. DESIGN/METHODOLOGY/APPROACH: The review was constructed by using primary and secondary terms to search the literature. The studies focused on peer support in custody with reference to mental health and self-injury. Searches identified papers on the prison listener scheme and staff perspectives on prison peer support, as these formed a central focus of the review. Studies were excluded from the review if the participants' behaviours was explicitly linked to suicidal intent, as the review focused on self-injury as a coping strategy. FINDINGS: A total of 24 studies were selected according to specific inclusion criteria (six were grey literature, 18 academic literature). Of the 24 studies ten studies focused on peer support and self-injury. Of the 24 studies the listener scheme was the focus of 16 studies, of these 16 studies self-injury and the listener scheme was a focus of eight studies. ORIGINALITY/VALUE: Evidence from the review suggests that prison peer support could be considered on a continuum depending on the different degrees of peer involvement. PMID- 26277924 TI - Emotional distress and sense of coherence in women completing a motivational program in five countries. A prospective study. AB - PURPOSE: The purpose of this paper is to investigate changes in, and associations between, sense of coherence (SOC) and emotional distress in women who participated in an accredited motivational program (VINN) in correctional institutions in five countries. DESIGN/METHODOLOGY/APPROACH: A prospective study with a pre- and post-test design included 316 participants from Sweden, Estonia, Denmark, Russia and Norway. Global emotional distress was measured by the Hospital Anxiety and Depression Scale. SOC was measured using the 13-item Orientation to Life Questionnaire. One-way analysis of variance and multilevel regression models were used in the statistical analyses. FINDINGS: An increase in SOC was associated with a decrease in emotional distress. Emotional distress decreased significantly -3.80 points (95 percent CI (-4.61, -2.97)), and SOC significantly improved from pre- to post-measurement by 1.82 points (95 percent CI (0.72, 2.92)), regardless of country and correctional institution. Practical implications - The results add new knowledge regarding a coherent theoretical foundation of a motivational program for women. The ability of a program promoting health is important for researchers, health-care workers and facilitators delivering programs for women in correctional facilities. An increase in SOC can act as a protective factor in order to manage stressors and risk factors among women serving in correctional facilities. ORIGINALITY/VALUE: The present study indicates that enhancing women's coping resources and providing income alternatives to crime is fundamental to their capacity to desist from criminal behavior. PMID- 26277925 TI - Community reentry challenges after release from prison among people who inject drugs in St. Petersburg, Russia. AB - PURPOSE: Little is known about the context of the post-release risk environment among formerly incarcerated people who inject drugs (PWID) in Russia. The purpose of this paper is to explore these challenges as they relate to reentry, relapse to injection opioid use, and overdose. DESIGN/METHODOLOGY/APPROACH: The authors conducted 25 in-depth semi-structured interviews among PWID living in St Petersburg, Russia who had been incarcerated within the past two years. Participants were recruited from street outreach (n=20) and a drug treatment center (n=5). FINDINGS: Emergent themes related to the post-release environment included financial instability, negative interactions with police, return to a drug using community, and reuniting with drug using peers. Many respondents relapsed to opioid use immediately after release. Those whose relapse occurred weeks or months after their release expressed more motivation to resist. Alcohol or stimulant use often preceded the opioid relapse episode. Among those who overdosed, alcohol use was often reported prior to overdosing on opioids. PRACTICAL IMPLICATIONS: Future post-release interventions in Russia should effectively link PWID to social, medical, and harm reduction services. Particular attention should be focussed on helping former inmates find employment and overdose prevention training prior to leaving prison that should also cover the heightened risk of concomitant alcohol use. ORIGINALITY/VALUE: In addition to describing a syndemic involving the intersection of incarceration, injection drug use, poverty, and alcohol abuse, the findings can inform future interventions to address these interrelated public health challenges within the Russian setting. PMID- 26277926 TI - Kiwifruit fibre level influences the predicted production and absorption of SCFA in the hindgut of growing pigs using a combined in vivo-in vitro digestion methodology. AB - Combined in vivo (ileal cannulated pig) and in vitro (faecal inoculum-based fermentation) digestion methodologies were used to predict the production and absorption of SCFA in the hindgut of growing pigs. Ileal and faecal samples were collected from animals (n 7) fed diets containing either 25 or 50 g/kg DM of kiwifruit fibre from added kiwifruit for 14 d. Ileal and faecal SCFA concentrations normalised for food DM intake (DMI) and nutrient digestibility were determined. Ileal digesta were collected and fermented for 38 h using a fresh pig faecal inoculum to predict SCFA production. The predicted hindgut SCFA production along with the determined ileal and faecal SCFA were then used to predict SCFA absorption in the hindgut and total tract organic matter digestibility. The determined ileal and faecal SCFA concentrations (e.g. 8.5 and 4.4 mmol/kg DMI, respectively, for acetic acid for the low-fibre diet) represented only 0.2-3.2 % of the predicted hindgut SCFA production (e.g. 270 mmol/kg DMI for acetic acid). Predicted production and absorption of acetic, butyric and propionic acids were the highest for the high-fibre diet (P0.05). In conclusion, determined ileal and faecal SCFA concentrations represent only a small fraction of total SCFA production, and may therefore be misleading in relation to the effect of diets on SCFA production and absorption. Considerable quantities of SCFA are produced and absorbed in the hindgut of the pig by the fermentation of kiwifruit. PMID- 26277927 TI - Hydrothermal Synthesis of Boron and Nitrogen Codoped Hollow Graphene Microspheres with Enhanced Electrocatalytic Activity for Oxygen Reduction Reaction. AB - Boron and nitrogen codoped hollow graphene microspheres (NBGHSs), synthesized from a simple template sacrificing method, have been employed as an electrocatalyst for the oxygen reduction reaction (ORR). Because of their specific hollow structure that consists of boron and nitrogen codoped graphene, the NBGHSs can exhibit even high electrocatalytic activity toward ORR than the commercial JM Pt/C 40 wt %. This, along with their higher stability, makes the NBGHSs particularly attractive as the electrocatalyst for the ORR with great potential to replace the commonly used noble-metal-based catalysts. PMID- 26277928 TI - Expression of Antioxidant Genes in the Mouse Cochlea and Brain in Salicylate Induced Tinnitus and Effect of Treatment with Spirulina platensis Water Extract. AB - Salicylate increased manganese-superoxide dismutase (Mn-SOD) gene expression, but decreased catalase (CAT) gene expression in the cochlea and various brain regions of mice with tinnitus. Spirulinaplatensis water extract reduced salicylate induced overexpression of the Mn-SOD gene, but increased salicylate-induced downregulation of the CAT gene. With the exception of significantly increased SOD activity in the brainstem and inferior colliculus of the Spirulina group, SOD and CAT enzyme activities did not differ among the three groups. The tinnitus group had higher malondialdehyde (MDA) levels than the control group in the temporal and the frontal lobes. S.platensis water extract reduced salicylate-induced elevations of MDA levels in many brain areas. We proposed that altered expression of antioxidant genes may reflect states of oxidative stress associated with tinnitus. PMID- 26277929 TI - Chromosomal Mapping of Repetitive DNAs in Characidium (Teleostei, Characiformes): Genomic Organization and Diversification of ZW Sex Chromosomes. AB - The speciose neotropical genus Characidium has proven to be a good model for cytogenetic exploration. Representatives of this genus often have a conserved diploid chromosome number; some species exhibit a highly differentiated ZZ/ZW sex chromosome system, while others do not show any sex-related chromosome heteromorphism. In this study, chromosome painting using a W-specific probe and comparative chromosome mapping of repetitive sequences, including ribosomal clusters and 4 microsatellite motifs - (CA)15, (GA)15, (CG)15, and (TTA)10 -, were performed in 6 Characidium species, 5 of which possessed a heteromorphic ZW sex chromosome system. The W-specific probe showed hybridization signals on the W chromosome of all analyzed species, indicating homology among the W chromosomes. Remarkably, a single major rDNA-bearing chromosome pair was found in all species. The 18S rDNA localized to the sex chromosomes in C. lanei, C. timbuiense and C. pterostictum, while the major rDNA localized to one autosome pair in C. vidali and C. gomesi. In contrast, the number of 5S rDNA-bearing chromosomes varied. Notably, minor ribosomal clusters were identified in the W chromosome of C. vidali. Microsatellites were widely distributed across almost all chromosomes of the karyotypes, with a greater accumulation in the subtelomeric regions. However, clear differences in the abundance of each motif were detected in each species. In addition, the Z and W chromosomes showed the differential accumulation of distinct motifs. Our results revealed variability in the distribution of repetitive DNA sequences and their possible association with sex chromosome diversification in Characidium species. PMID- 26277930 TI - Common Variants in Serum/Glucocorticoid Regulated Kinase 1 (SGK1) and Blood Pressure Responses to Dietary Sodium or Potassium Interventions: A family-Based Association Study. AB - BACKGROUND/AIMS: Serum/Glucocorticoid Regulated Kinase 1 (SGK1) plays a significant role in regulating renal Na(+) reabsorption, K(+) secretion, and blood pressure (BP). This study aimed to assess the association of common genetic variants in the SGK1 gene with BP responses to controlled dietary sodium or potassium interventions. METHODS: A total of 334 subjects from 124 families were recruited from the rural areas of northern China. After a three-day baseline observation, they were sequentially maintained a seven-day low-sodium diet (3g/day of NaCl or 51.3 mmol/day of sodium), a seven-day high-sodium diet (18 g/day of NaCl or 307.8 mmol/day of sodium) and a seven-day high-sodium plus potassium supplementation intervention (4.5 g/day of KCl or 60 mmol/day of potassium). Six single-nucleotide polymorphisms (SNPs) in the SGK1 gene were selected. RESULTS: After adjustment for multiple testing, SNP rs9376026 was significantly associated with diastolic BP (DBP) and mean arterial pressure (MAP) responses to low-sodium intervention (P = 0.018 and 0.022, respectively). However, the associations between selected SNPs in the SGK1 gene and BP responses to high-sodium or high-sodium plus potassium-supplementation intervention did not reach statistical significance. In addition, SNP rs9389154 and two other SNPs (rs1763509 and rs9376026) were associated respectively with systolic BP (SBP) and DBP at baseline (P = 0.040, 0.032, and 0.031, respectively). SNP rs3813344 was significantly associated with SBP, DBP, and MAP (P = 0.049, 0.015 and 0.018, respectively). CONCLUSION: Our study indicates that the genetic polymorphism in the SGK1 gene is significantly associated with BP responses to dietary sodium intervention. PMID- 26277931 TI - Study of the True Clinical Progression of Autosomal Dominant Alport Syndrome in a European Population. AB - BACKGROUND/AIMS: Autosomal dominant Alport syndrome represents 5% of all Alport syndrome cases. This entity presents a different clinical expression from the recessive inheritance pattern and the X chromosome-linked pattern, because it is mild and it shows a late onset, which in many cases even goes unnoticed. METHODS: We carried out a descriptive observational and retrospective clinical study on 19 patients from 5 families with a clinical diagnosis of autosomal dominant Alport Syndrome, and we analyzed the expression of the symptoms in the different families, comparing the results with what has been described in the literature. RESULTS: Renal involvement appeared at a young age, with a progression towards end-stage chronic kidney disease at a median age of 31 years (20.5-36.5). Hearing involvement also appeared in early stages, at a median age of 28.5 years (7.5 62.5). Also, we observed ocular lenticonus-like injuries, which until now have only been described in other inheritance patterns. CONCLUSIONS: Our results suggest that dominant patterns are accompanied by a severe clinical expression that can be superimposed to the recessive and X chromosome-linked patterns, contrary to what has been classically stated. The high phenotypic variability observed in the families lead to the fact that many cases go unnoticed and the severest cases are erroneously diagnosed as recessive, which means that the real prevalence of dominant forms is probably higher than the current 5%. PMID- 26277932 TI - Propofol Prevents Renal Ischemia-Reperfusion Injury via Inhibiting the Oxidative Stress Pathways. AB - BACKGROUND/AIMS: Renal ischemia/reperfusion injury (IRI) is a risk for acute renal failure and delayed graft function in renal transplantation and cardiac surgery. The purpose of this study is to determine whether propofol could attenuate renal IRI and explore related mechanism. METHODS: Male rat right kidney was removed, left kidney was subjected to IRI. Propofol was intravenously injected into rats before ischemia. The kidney morphology and renal function were analyzed. The expression of Bax, Bcl-2, caspase-3, cl-caspase-3, GRP78, CHOP and caspase-12 were detected by Western blot analysis. RESULTS: IR rats with propofol pretreatment had better renal function and less tubular apoptosis than untreated IR rats. Propofol pretreated IR rats had lower Bax/Bcl-2 ratio and less cleaved caspase-3. The protein expression levels of GRP78, CHOP and caspase-12 decreased significantly in propofol pretreated IR rats. In vitro cell model showed that propofol significantly increased the viability of NRK-52E cells that were subjected to hypoxia/reoxygenation (H/R) in a dose-dependent manner. The effect of propofol on the expression regulation of Bax, Bcl-2, caspase-3, GRP78, CHOP was consistent in both in vitro and in vivo models. CONCLUSION: Experimental results suggest that propofol prevents renal IRI via inhibiting oxidative stress. PMID- 26277933 TI - Twin-Twin Transfusion Syndrome in Cases with Suspected Close Proximity of Umbilical Cord Insertions. AB - We encountered 3 cases of twin-twin transfusion syndrome (TTTS), in which preoperative ultrasonography revealed that the cord insertion sites of the twins were close. Two cases were successfully treated with fetoscopic laser photocoagulation (FLP); however, the third case could not be treated surgically because fetoscopy revealed that the cord insertions formed a V-shaped joint above the placenta and that all chorionic vessels of the placental surface were shared by the twins. No residual anastomoses were detected on placental examination in the 2 cases treated with FLP. Our experiences indicate that the feasibility of FLP could be evaluated using fetoscopy, not just ultrasonography, in cases of TTTS accompanied by proximate umbilical cord insertion. PMID- 26277935 TI - Heterogeneous Reactivity of Nitric Acid with Nascent Sea Spray Aerosol: Large Differences Observed between and within Individual Particles. AB - Current climate and atmospheric chemistry models assume that all sea spray particles react as if they are pure NaCl. However, recent studies of sea spray aerosol particles have shown that distinct particle types exist (including sea salt, organic carbon, and biological particles) as well as mixtures of these and, within each particle type, there is a range of single-particle chemical compositions. Because of these differences, individual particles should display a range of reactivities with trace atmospheric gases. Herein, to address this, we study the composition of individual sea spray aerosol particles after heterogeneous reaction with nitric acid. As expected, a replacement reaction of chloride with nitrate is observed; however, there is a large range of reactivities spanning from no reaction to complete reaction between and within individual sea spray aerosol particles. These data clearly support the need for laboratory studies of individual, environmentally relevant particles to improve our fundamental understanding as to the properties that determine reactivity. PMID- 26277934 TI - The role of semantically related distractors during encoding and retrieval of words in long-term memory. AB - We examined the influence of divided attention (DA) on recognition of words when the concurrent task was semantically related or unrelated to the to-be-recognised target words. Participants were asked to either study or retrieve a target list of semantically related words while simultaneously making semantic decisions (i.e., size judgements) to another set of related or unrelated words heard concurrently. We manipulated semantic relatedness of distractor to target words, and whether DA occurred during the encoding or retrieval phase of memory. Recognition accuracy was significantly diminished relative to full attention, following DA conditions at encoding, regardless of relatedness of distractors to study words. However, response times (RTs) were slower with related compared to unrelated distractors. Similarly, under DA at retrieval, recognition RTs were slower when distractors were semantically related than unrelated to target words. Unlike the effect from DA at encoding, recognition accuracy was worse under DA at retrieval when the distractors were related compared to unrelated to the target words. Results suggest that availability of general attentional resources is critical for successful encoding, whereas successful retrieval is particularly reliant on access to a semantic code, making it sensitive to related distractors under DA conditions. PMID- 26277936 TI - Preparation of Single-Phase Films of CH3NH3Pb(I1-xBrx)3 with Sharp Optical Band Edges. AB - Organometallic lead-halide perovskite-based solar cells now approach 18% efficiency. Introducing a mixture of bromide and iodide in the halide composition allows tuning of the optical bandgap. We prepare mixed bromide-iodide lead perovskite films CH3NH3Pb(I1-xBrx)3 (0 <= x <= 1) by spin-coating from solution and obtain films with monotonically varying bandgaps across the full composition range. Photothermal deflection spectroscopy, photoluminescence, and X-ray diffraction show that following suitable fabrication protocols these mixed lead halide perovskite films form a single phase. The optical absorption edge of the pure triiodide and tribromide perovskites is sharp with Urbach energies of 15 and 23 meV, respectively, and reaches a maximum of 90 meV for CH3NH3PbI1.2Br1.8. We demonstrate a bromide-iodide lead perovskite film (CH3NH3PbI1.2Br1.8) with an optical bandgap of 1.94 eV, which is optimal for tandem cells of these materials with crystalline silicon devices. PMID- 26277937 TI - Boosting the Efficiency of Suspended Photocatalysts for Overall Water Splitting. PMID- 26277938 TI - A Stable, Magnetic, and Metallic Li3O4 Compound as a Discharge Product in a Li Air Battery. AB - The Li-air battery with the specific energy exceeding that of a Li ion battery has been aimed as the next-generation battery. The improvement of the performance of the Li-air battery needs a full resolution of the actual discharge products. Li2O2 has been long recognized as the main discharge product, with which, however, there are obvious failures on the understanding of various experimental observations (e.g., magnetism, oxygen K-edge spectrum, etc.) on discharge products. There is a possibility of the existence of other Li-O compounds unknown thus far. Here, a hitherto unknown Li3O4 compound as a discharge product of the Li-air battery was predicted through first-principles swarm structure searching calculations. The new compound has a unique structure featuring the mixture of superoxide O2(-) and peroxide O2(2-), the first such example in the Li-O system. The existence of superoxide O2(-) creates magnetism and hole-doped metallicity. Findings of Li3O4 gave rise to direct explanations of the unresolved experimental magnetism, triple peaks of oxygen K-edge spectra, and the Raman peak at 1125 cm( 1) of the discharge products. Our work enables an opportunity for the performance of capacity, charge overpotential, and round-trip efficiency of the Li-air battery. PMID- 26277939 TI - Stabilized Lithium-Metal Surface in a Polysulfide-Rich Environment of Lithium Sulfur Batteries. AB - Lithium-metal anode degradation is one of the major challenges of lithium-sulfur (Li-S) batteries, hindering their practical utility as next-generation rechargeable battery chemistry. The polysulfide migration and shuttling associated with Li-S batteries can induce heterogeneities of the lithium-metal surface because it causes passivation by bulk insulating Li2S particles/electrolyte decomposition products on a lithium-metal surface. This promotes lithium dendrite formation and leads to poor lithium cycling efficiency with complicated lithium surface chemistry. Here, we show copper acetate as a surface stabilizer for lithium metal in a polysulfide-rich environment of Li-S batteries. The lithium surface is protected from parasitic reactions with the organic electrolyte and the migrating polysulfides by an in situ chemical formation of a passivation film consisting of mainly Li2S/Li2S2/CuS/Cu2S and electrolyte decomposition products. This passivation film also suppresses lithium dendrite formation by controlling the lithium deposition sites, leading to a stabilized lithium surface characterized by a dendrite-free morphology and improved surface chemistry. PMID- 26277940 TI - Ligand-Mediated Ring -> Cube Transformation in a Catalytic Subnanocluster: Co4O4(MeCN)n with n = 1-6. AB - We studied the Co4O4 subnanocluster and its MeCN-coated species using density functional theory, and we found that the Co4O4 core presents distinctive structures in bare and ligand-coated species. We propose a possible ligand mediated ring -> cube transformation mechanism during the ligand-coating process of the Co4O4 core due to the stronger binding energies of the MeCN ligands to the 3D distorted cube structure than to the 2D ring and ladder structures; theory indicates that three ligands are sufficient to stabilize the cube structure. Both ring and cube structures are ferromagnetic. Our finding is potentially useful for understanding the catalysis mechanism of Co4O4 species, which have important applications in solar energy conversion and water splitting; these catalysis reactions usually involve frequent addition and subtraction of various ligands and thus possibly involve core rearrangement processes similar to our findings. PMID- 26277941 TI - Recent Progress in Two-Dimensional Oxide Photocatalysts for Water Splitting. AB - This Perspective focuses on the photocatalytic activity of two-dimensional (2D) oxide and nitrogen-doped oxide crystals and the effective use of 2D photocatalysts for understanding the mechanism of the water splitting reaction. Strategies for improving the activities of 2D photocatalysts are slightly different from those of bulk photocatalysts. Although it is well-known that a photocatalyst without co-catalyst loading has low activity for hydrogen production from water, a certain type of 2D oxide nanosheet shows high activity without co-catalyst loading. It is difficult to determine what factors contribute to this separation of oxidation and reduction sites of water because there are many factors on the reaction surface. A nanosheet p-n junction surface is an ideal surface for understanding the carrier transfer during the photocatalytic reaction. In this system, the driving force of the carrier transfer to the reaction sites was found to be the potential gradient generated by the nanosheet junction. PMID- 26277942 TI - New Insights into the Mechanism of Visible Light Photocatalysis. AB - In recent years, the area of developing visible-light-active photocatalysts based on titanium dioxide has been enormously investigated due to its wide range of applications in energy and environment related fields. Various strategies have been designed to efficiently utilize the solar radiation and to enhance the efficiency of photocatalytic processes. Building on the fundamental strategies to improve the visible light activity of TiO2-based photocatalysts, this Perspective aims to give an insight into many contemporary developments in the field of visible-light-active photocatalysis. Various examples of advanced TiO2 composites have been discussed in relation to their visible light induced photoconversion efficiency, dynamics of electron-hole separation, and decomposition of organic and inorganic pollutants, which suggest the critical need for further development of these types of materials for energy conversion and environmental remediation purposes. PMID- 26277943 TI - Electronic Structure of Aqueous Sulfuric Acid from First-Principles Simulations with Hybrid Functionals. PMID- 26277944 TI - Asymmetric Transport Mechanisms of Hydronium and Hydroxide Ions in Amorphous Solid Water: Hydroxide Goes Brownian while Hydronium Hops. AB - The diffusion of hydronium (H3O(+)) and hydroxide (OH(-)) ions is one of the most intriguing topics in aqueous chemistry. It is considered that these ions in aqueous solutions move via sequential proton transfer events, known as the Grotthuss mechanisms. Here, we present an experimental study of the diffusion and H/D exchange of hydronium and hydroxide ions in amorphous solid water (ASW) at 140-180 K by using low-energy sputtering (LES) and temperature-programmed desorption (TPD) measurements. The study shows that the two species transport in ASW via fundamentally different molecular mechanisms. Whereas hydronium ions migrate via efficient proton transfer, hydroxide ions move via Brownian molecular diffusion without proton transfer. The molecular hydroxide diffusion in ASW is in stark contrast to the current view of the hydroxide diffusion mechanism in aqueous solution, which involves proton transfer. PMID- 26277945 TI - Use of Isotope-Edited FTIR to Derive a Backbone Structure of a Transmembrane Protein. AB - Solving structures of membrane proteins has always been a formidable challenge, yet even upon success, the results are normally obtained in a mimetic environment that can be substantially different from a biological membrane. Herein, we use noninvasive isotope-edited FTIR spectroscopy to derive a structural model for the SARS coronavirus E protein transmembrane domain in lipid bilayers. Molecular dynamics-based structural refinement, incorporating the IR-derived orientational restraints points to the formation of a helical hairpin structure. Disulfide cross-linking and X-ray reflectivity depth profiling provide independent support of the results. The unusually short helical hairpin structure of the protein might explain its ability to deform bilayers and is reminiscent of other peptides with membrane disrupting functionalities. Taken together, we show that isotope edited FTIR is a powerful tool to analyze small membrane proteins in their native environment, enabling us to relate the unusual structure of the SARS E protein to its function. PMID- 26277946 TI - Multiexciton Generation in Seeded Nanorods. AB - The stochastic formulation of multiexciton generation (MEG) rates is extended to provide access to MEG efficiencies in nanostructures containing thousands of atoms. The formalism is applied to a series of CdSe/CdS seeded nanorod heterostructures with different core and shell dimensions. At energies above 3Eg (where Eg is the band gap), the MEG yield increases with decreasing core size, as expected for spherical nanocrystals. Surprisingly, this behavior is reversed for energies below this value, and is explained by the dependence of the density of states near the valence band edge, which increases with the core diameter. Our predictions indicate that the onset of MEG can be shifted to lower energies by manipulating the density of states in complex nanostructure geometries. PMID- 26277947 TI - Higher Excited States in Multiphoton Photochemical Reactions "Hint" Toward Rapid Chemistry. PMID- 26277948 TI - Direct Observation of Ultrafast Excimer Formation in Covalent Perylenediimide Dimers Using Near-Infrared Transient Absorption Spectroscopy. AB - Energy transfer in perylene-3,4:9,10-bis(dicarboximide) (PDI) aggregates is often limited by formation of a low-energy excimer state. Formation dynamics of excimer states are often characterized by line shape changes and peak shift dynamics in femtosecond visible transient absorption spectra. Femtosecond near-infrared transient absorption experiments reveal a unique low-energy transition that can be used to identify and characterize this state without overlapping excited singlet-state absorption. Three covalently bound PDI dimers with differing PDI PDI distances were studied to probe the influence of interchromophore electronic coupling on the PDI excimer transient spectra and dynamics. PMID- 26277949 TI - Plasmon Resonance Hybridization of Gold Nanospheres and Palladium Nanoshells Combined in a Rattle Structure. AB - Gold and palladium nanoparticles are characterized by their localized surface plasmon resonance (LSPR). In contrast with the sharp LSPR spectrum of gold nanoparticles, palladium nanoparticles had a broad LSPR spectrum. Palladium-gold nanorattles (PdAuNRT) are an ideal system with optical properties that are a hybrid of gold and palladium nanoparticles. The PdAuNRTs consisted of small gold nanospheres (AuNSs) located inside hollow palladium nanospheres (PdHNSs) of larger sizes without touching each other. PdAuNRTs of various sizes were synthesized by systematic variation of the experimental parameters. Interestingly, for the PdAuNRTs, where PdHNSs and AuNSs are separated by a distance, it was found that the broad plasmon resonance band of the PdHNSs hybridizes with the sharp plasmon resonance of the AuNSs located in its center. This was further confirmed experimentally by optical absorption measurements and theoretically using discrete dipole approximation technique. The plasmon resonance hybridization resulted in broadening of the LSPR spectrum of the PdAuNRTs and the appearance of a dip due to a Fano resonance. PMID- 26277950 TI - Next-Generation Epigenetic Detection Technique: Identifying Methylated Cytosine Using Graphene Nanopore. AB - DNA methylation plays a pivotal role in the genetic evolution of both embryonic and adult cells. For adult somatic cells, the location and dynamics of methylation have been very precisely pinned down with the 5-cytosine markers on cytosine-phosphate-guanine (CpG) units. Unusual methylation on CpG islands is identified as one of the prime causes for silencing the tumor suppressant genes. Early detection of methylation changes can diagnose the potentially harmful oncogenic evolution of cells and provide promising guideline for cancer prevention. With this motivation, we propose a cytosine methylation detection technique. Our hypothesis is that electronic signatures of DNA acquired as a molecule translocates through a nanopore would be significantly different for methylated and nonmethylated bases. This difference in electronic fingerprints would allow for reliable real-time differentiation of methylated DNA. We calculate transport currents through a punctured graphene membrane while the cytosine and methylated cytosine translocate through the nanopore. We also calculate the transport properties for uracil and cyanocytosine for comparison. Our calculations of transmission, current, and tunneling conductance show distinct signatures in their spectrum for each molecular type. Thus, in this work, we provide a theoretical analysis that points to a viability of our hypothesis. PMID- 26277951 TI - Two-Dimensional Anisotropy Measurements Showing Local Heterogeneity in a Polymer Melt. AB - In polymers, the rotation of a small solute is nonexponential. Either heterogeneity in the local friction or local anisotropy-a homogeneous process-may be responsible. A new, two-dimensional anisotropy experiment is demonstrated on this problem. In poly(dimethylsiloxane), the rotation of individual solute molecules is found to be exponential, and the observed rate dispersion is primarily due to variation in the local friction. This sample is far from its glass transition. Studies of rate heterogeneity associated with the glass transition must account for the contribution from this polymer-related mechanism. PMID- 26277952 TI - Gasification Mechanism of Carbon with Supercritical Water at Very High Pressures: Effects on H2 Production. AB - The scarce data concerning the gasification of carbonaceous solids with supercritical water (SCW) suggest the great potential of this method to produce a valuable green fuel such as H2. However, the extraordinary properties of SCW have not been properly applied to H2 production because the mechanism that governs gasification under these conditions remains unclear. Here, we present a study in which this reaction is explored within the largest pressure range ever assayed in this field, from 1 to 1000 bar. The amplitude of the experimental conditions investigated highlights the various pathways that govern gasification with steam and SCW. Under supercritical conditions, the clusters formed around the superficial groups of the solid reduce the energetic requirements for gasification and generate CO2 as a primary product of the reaction. Consequently, gasification with SCW is significantly faster than that using steam, and the produced gases are richer and more appropriate to obtain pure H2. PMID- 26277953 TI - First-Principles Investigation of the TiO2/Organohalide Perovskites Interface: The Role of Interfacial Chlorine. AB - We investigate the prototypical interface between organohalide perovskites and TiO2 by first-principles electronic structure calculations. The investigated heterointerface is representative of conventional dye-sensitized solar cells based on a mesoporous TiO2 scaffold and of flat devices in which a compact TiO2 film is used as electron selective layer. We find that the MAPbI3 and MAPbI3-xClx perovskites tend to grow in (110)-oriented films on TiO2, due to the better structural matching between rows of adjacent perovskite surface halides and TiO2 undercoordinated titanium atoms. Interfacial chlorine atoms further stabilize the (110) surface, due to an enhanced binding energy. We find that the stronger interaction of MAPbI3-xClx with TiO2 modifies the interface electronic structure, leading to a stronger interfacial coupling and to a slight TiO2 conduction band energy upshift. Our modeling study may constitute the basis for a further exploitation of perovskite solar cells. PMID- 26277954 TI - Influence of Step Geometry on the Reconstruction of Stepped Platinum Surfaces under Coadsorption of Ethylene and CO. AB - We demonstrate the critical role of the specific atomic arrangement at step sites in the restructuring processes of low-coordinated surface atoms at high adsorbate coverage. By using high-pressure scanning tunneling microscopy (HP-STM) and ambient-pressure X-ray photoelectron spectroscopy (AP-XPS), we have investigated the reconstruction of Pt(332) (with (111)-oriented triangular steps) and Pt(557) surfaces (with (100)-oriented square steps) in the mixture of CO and C2H4 in the Torr pressure range at room temperature. CO creates Pt clusters at the step edges on both surfaces, although the clusters have different shapes and densities. A subsequent exposure to a similar partial pressure of C2H4 partially reverts the clusters on Pt(332). In contrast, the cluster structure is barely changed on Pt(557). These different reconstruction phenomena are attributed to the fact that the 3-fold (111)-step sites on Pt(332) allows for adsorption of ethylidyne-a strong adsorbate formed from ethylene-that does not form on the 4-fold (100)-step sites on Pt(557). PMID- 26277955 TI - Spatial Mapping of Flow-Induced Molecular Alignment in a Noncrystalline Biopolymer Fluid Using Double Quantum Filtered (DQF) (23)Na MRI. AB - Flow-induced molecular alignment was observed experimentally in a non-liquid crystalline bioplymeric fluid during developed tubular flow. The fluid was comprised of rigid rods of the polysaccharide xanthan and exhibited shear thinning behavior. Without a requirement for optical transparency or the need for an added tracer, (23)Na magic angle (MA) double quantum filtered (DQF) magnetic resonance imaging (MRI) enabled the mapping of the anisotropic molecular arrangement under flow conditions. A regional net molecular alignment was found in areas of high shear values in the vicinity of the tube wall. Furthermore, the xanthan molecules resumed random orientations after the cessation of flow. The observed flow-induced molecular alignment was correlated with the rheological properties of the fluid. The work demonstrates the ability of (23)Na MA DQF magnetic resonance to provide a valuable molecular-mechanical link. PMID- 26277956 TI - Charge Diffusion in Semiconducting Polymers: Analytical Relation between Polymer Rigidity and Time Scales for Intrachain and Interchain Hopping. AB - We study the charge diffusion of semiconducting polymer bulk using simplified coarse grained models to investigate the relation between charge diffusion coefficient and the characteristics time of intrachain and interchain hopping, tau1 and tau2. We consider the process of charge diffusion in several standard models of polymer chains (rigid chain, Gaussian chain, worm-like chain), and we achieve an analytical expression for the diffusion coefficient in terms of the characteristic times and the geometric parameters defining the chain models. The diffusion depends only on the intrachain hopping for the rigid chain and on the geometric average of intrachain and interchain hopping times for the Gaussian chain (the least rigid model), with an analytical interpolation available between two limits. The model highlights the importance of large persistence lengths for improved transport properties. In all cases, it is incorrect to consider the slower interchain hopping as the rate-determining step for the charge transport. PMID- 26277957 TI - Cage-Like Nanoclusters of ZnO Probed by Time-Resolved Photoelectron Spectroscopy and Theory. AB - Zinc oxide nanoclusters have been predicted as promising building blocks for cluster-assembled materials with unprecedented properties. Here, for the first time these clusters are probed by time-resolved photoelectron spectroscopy and characterized in detail by density functional theory. Their validity as building blocks for cluster-assembled materials is confirmed via rigid cage-like structures facilitating three-dimensional aggregation in combination with large band gaps that are nevertheless significantly lower than any known ZnO polymorph. In addition, electron-hole pair localization in the excited state of the cluster anions combined with their structural rigidity leads to extraordinary long-lived states above the band gap virtually independent of the cluster size, defying the rule "every atom counts". PMID- 26277958 TI - Charge Separation and Exciton Dynamics at Polymer/ZnO Interface from First Principles Simulations. AB - Charge separation and exciton dynamics play a crucial role in determining the performance of excitonic photovoltaics. Using time-dependent density functional theory with a range-separated exchange-correlation functional as well as nonadiabatic ab initio molecular dynamics, we have studied the formation and dynamics of charge-transfer (CT) excitons at polymer/ZnO interface. The interfacial atomic structure, exciton density of states and conversions between exciton species are examined from first-principles. The exciton dynamics exhibits both adiabatic and nonadiabatic characters. While the adiabatic transitions are facilitated by C?C vibrations along the polymer (P3HT) backbone, the nonadiabatic transitions are realized by exciton hopping between the excited states. We find that the localized ZnO surface states lead to localized low-energy CT states and poor charge separation. In contrast, the surface states of crystalline C60 are indistinguishable from the bulk states, resulting in delocalized CT states and efficient charge separation in polymer/fullerene (P3HT/PCBM) heterojunctions. The hot CT states are found to cool down in an ultrafast time scale and may not play a major role in charge separation of P3HT/ZnO. Finally we suggest that the dimensions of nanostructured acceptors can be tuned to obtain both efficient charge separation and high open circuit voltages. PMID- 26277959 TI - Ultrahigh Vacuum Tip-Enhanced Raman Spectroscopy with Picosecond Excitation. AB - Tip-enhanced Raman spectroscopy (TERS) provides chemical information about adsorbates with nanoscale spatial resolution, but developments are still required in order to incorporate ultrafast temporal resolution. In this Letter, we demonstrate that a reliable TER signal of rhodamine 6G (R6G) using picosecond (ps)-pulsed excitation can be obtained in ultrahigh vacuum (UHV). In contrast to our previous observation of irreversible signal loss in ambient TERS ( Klingsporn , J. M. ; Sonntag , M. D. ; Seideman , T. ; Van Duyne , R. P. J. Phys. Chem. Lett. 2014 , 5 , 106 - 110 ), we demonstrate that the UHV environment decreases irreversible signal degradation. As a complement to the TERS experiments, we examined the rate of surface-enhanced Raman (SER) signal decay under picosecond irradiation and found that it is also slowed in UHV compared to that in ambient. Signal decay kinetics suggest that the predominant mechanism responsible for signal loss in ps SERS of R6G is surface diffusion. Both diffusive and reactive phenomena can lead to pulsed excitation TER signal loss, and a UHV environment is advantageous in either scenario. PMID- 26277960 TI - Extremely Slow Photoconductivity Response of CH3NH3PbI3 Perovskites Suggesting Structural Changes under Working Conditions. AB - Photoconductivity measurements of CH3NH3PbI3 deposited between two dielectric protected Au electrodes show extremely slow response. The CH3NH3PbI3, bridging a gap of ~2000 nm, was subjected to a DC bias and cycles of 5 min illumination and varying dark duration. The approach to steady -state photocurrent lasted tens of seconds with a strong dependence on the dark duration preceding the illumination. On the basis of DFT calculations, we propose that under light + bias the methylammonium ions are freed to rotate and align along the electric field, thus modifying the structure of the inorganic scaffold. While ions alignment is expected to be fast, the adjustment of the inorganic scaffold seems to last seconds as reflected in the extremely slow photoconductivity response. We propose that under working conditions a modified, photostable, perovskite structure is formed, depending on the bias and illumination parameters. Our findings seem to clarify the origin of the well-known hysteresis in perovskite solar cells. PMID- 26277961 TI - First-Principles, Physically Motivated Force Field for the Ionic Liquid [BMIM][BF4]. AB - Molecular simulations play an important role in establishing structure-property relations in complex fluids such as room-temperature ionic liquids. Classical force fields are the starting point when large systems or long times are of interest. These force fields must be not only accurate but also transferable. In this work, we report a physically motivated force field for the ionic liquid 1 butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]) based on symmetry adapted perturbation theory. The predictions (from molecular dynamics simulations) of the liquid density, enthalpy of vaporization, diffusion coefficients, viscosity, and conductivity are in excellent agreement with experiment, with no adjustable parameters. The explicit energy decomposition inherent in the force field enables a quantitative analysis of the important physical interactions in these systems. We find that polarization is crucial and there is little evidence of charge transfer. We also argue that the often used procedure of scaling down charges in molecular simulations of ionic liquids is unphysical for [BMIM][BF4]. Because all intermolecular interactions in the force field are parametrized from first-principles, we anticipate good transferability to other ionic liquid systems and physical conditions. PMID- 26277962 TI - Phosphorene as a Superior Gas Sensor: Selective Adsorption and Distinct I-V Response. AB - Recent reports on the fabrication of phosphorene, that is, mono- or few-layer black phosphorus, have raised exciting prospects of an outstanding two dimensional (2D) material that exhibits excellent properties for nanodevice applications. Here, we study by first-principles calculations the adsorption of CO, CO2, NH3, NO, and NO2 gas molecules on a monolayer phosphorene. Our results predict superior sensing performance of phosphorene that rivals or even surpasses that of other 2D materials such as graphene and MoS2. We determine the optimal adsorption positions of these molecules on the phosphorene and identify molecular doping, that is, charge transfer between the molecules and phosphorene, as the driving mechanism for the high adsorption strength. We further calculated the current-voltage (I-V) relation using the nonequilibrium Green's function (NEGF) formalism. The transport features show large (1-2 orders of magnitude) anisotropy along different (armchair or zigzag) directions, which is consistent with the anisotropic electronic band structure of phosphorene. Remarkably, the I-V relation exhibits distinct responses with a marked change of the I-V relation along either the armchair or the zigzag directions depending on the type of molecules. Such selectivity and sensitivity to adsorption makes phosphorene a superior gas sensor that promises wide-ranging applications. PMID- 26277963 TI - Intersystem Crossing Enables 4-Thiothymidine to Act as a Photosensitizer in Photodynamic Therapy: An Ab Initio QM/MM Study. AB - Motivated by its potential use as a photosensitizer in photodynamic therapy, we report the first ab initio quantum mechanics/molecular mechanics (QM/MM) study of 4-thiothymidine in aqueous solution. The core chromophore 4-thiothymine was described using the multiconfigurational CASSCF and CASPT2 QM methods, while the ribose and the solvent water molecules were treated at the MM level (CHARMM and TIP3P, respectively). The minima of the five lowest electronic states (S0, S1, S2, T1, and T2) and six minimum-energy intersections were fully optimized at the QM(CASSCF)/MM level, and their energies were further refined by single-point QM(CASPT2)/MM and CASPT2 calculations. The relevant spin-orbit couplings were also computed. We find that (1) there are three efficient photophysical pathways that account for the experimentally observed ultrafast formation of the lowest triplet state with a quantum yield of nearly unity, (2) the striking qualitative differences in the photophysical behavior of 4-thiothymine and thymine originate from the different electronic structure of their S1 states, and (3) environmental effects play an important role. The present QM/MM calculations provide mechanistic insight that may guide the design of improved photosensitizers for photodynamic therapy. PMID- 26277964 TI - Binary Solvent Organization at Silica/Liquid Interfaces: Preferential Ordering in Acetonitrile-Methanol Mixtures. AB - Nonlinear vibrational spectroscopy experiments examined solvent organization at the silica/binary solvent interface where the binary solvent consisted of methanol and acetonitrile in varying mole fractions. Data were compared with surface vibrational spectra acquired from silica surfaces exposed to a vapor phase saturated with the same binary solvent mixtures. Changes in vibrational band intensities suggest that methanol ideally adsorbs to the silica/vapor interface but acetonitrile accumulates in excess relative to vapor-phase composition. At the silica/liquid interface, acetonitrile's signal increases until a solution phase mole fraction of ~0.85. At higher acetonitrile concentrations, acetonitrile's signal decreases dramatically until only a weak signature persists with the neat solvent. This behavior is ascribed to dipole paired acetonitrile forming a bilayer with the first sublayer associating with surface silanol groups and a second sublayer consisting of weakly associating, antiparallel partners. On the basis of recent simulations, we propose that the second sublayer accumulates in excess. PMID- 26277965 TI - New Phases of Germanene. AB - Germanene, a graphene-like single-layer structure of Ge, has been shown to be stable and recently grown on Pt and Au substrates. We show that a Ge adatom adsorbed on germanene pushes down the host Ge atom underneath and forms a dumbbell structure. This exothermic process occurs spontaneously. The attractive dumbbell-dumbbell interaction favors high coverage of dumbbells. This Letter heralds stable new phases of germanene, which are constructed from periodically repeating coverage of dumbbell structures and display diversity of electronic and magnetic properties. PMID- 26277966 TI - Polymorphism of Crystalline Molecular Donors for Solution-Processed Organic Photovoltaics. AB - Using ab initio calculations and classical molecular dynamics simulations coupled to complementary experimental characterization, four molecular semiconductors were investigated in vacuum, solution, and crystalline form. Independently, the molecules can be described as nearly isostructural, yet in crystalline form, two distinct crystal systems are observed with characteristic molecular geometries. The minor structural variations provide a platform to investigate the subtlety of simple substitutions, with particular focus on polymorphism and rotational isomerism. Resolved crystal structures offer an exact description of intermolecular ordering in the solid state. This enables evaluation of molecular binding energy in various crystallographic configurations to fully rationalize observed crystal packing on a basis of first-principle calculations of intermolecular interactions. PMID- 26277967 TI - Raman Evidence for Late Stage Disproportionation in a Li-O2 Battery. AB - Raman spectroscopy is used to characterize the composition of toroids formed in an aprotic Li-O2 cell based on an activated carbon cathode. The trends in the Raman data as a function of discharge current density and charging cutoff voltage provide evidence that the toroids are made up of outer LiO2-like and inner Li2O2 regions, consistent with a disproportionation reaction occurring in the solid phase. The LiO2-like component is found to be associated with a new Raman peak identified in the carbon stretching region at ~1505 cm(-1), which appears only when the LiO2 peak at 1123 cm(-1) is present. The new peak is assigned to distortion of the graphitic ring stretching due to coupling with the LiO2-like component based on density functional calculations. These new results on the LiO2 like component from Raman spectroscopy provide evidence that a late stage disproportionation mechanism can occur during discharge and add new understanding to the complexities of possible processes occurring in Li-O2 batteries. PMID- 26277968 TI - Role of Charge Transfer in Water Diffusivity in Aqueous Ionic Solutions. AB - We performed molecular dynamics simulations on four types of systems containing ion and solvating water. Two systems contained a cation (Na(+) or K(+)), and two other systems an anion (Cl(-) or I(-)). Classical molecular dynamics simulations were performed using three different force fields: a fixed charge force field, a polarizable force field that includes explicit polarization, and also a recently developed force field that includes polarization and charge transfer. These simulations were then compared to first-principles molecular dynamics simulations. While the first-principles simulations showed that the anions accelerated water translational diffusion, the cations slowed it down. In simulations with the classical force fields, only the force field that incorporates explicit charge transfer reproduced this ion-specific behavior. Additional simulations performed to understand the effect of charge transfer demonstrated that two competitive factors determine the behavior of water translational diffusion: the ions diminished charge accelerates water, while the net charge acquired by water either accelerates or slows down its dynamics. Our results show that charge transfer plays a crucial role in governing the water dynamics in aqueous ionic solutions. PMID- 26277969 TI - Photophysics of Voltage Increase by Photoinduced Dipole Layers in Sensitized Solar Cells. AB - Significant overpotentials between the sensitizer and both the electron and hole conductors hamper the performance of sensitized solar cells, leading to a reduced photovoltage. We show that by using properly designed type-II quantum dots (QDs) between the sensitizer and the hole conductor in thin absorber cells, it is possible to increase the open circuit voltage (Voc) by more than 100 mV. This increase is due to the formation of a photoinduced dipole (PID) layer. Photogenerated holes in the type-II QDs are retained in the core for a relatively long time, allowing for the accumulation of a positively charged layer. Negative charges are, in turn, injected and accumulated in the TiO2 anode, creating a dipole moment, which negatively shifts the TiO2 conduction band relative to the electrolyte. We study this phenomenon using a unique TiO2/CdSe/(ZnSe:Te/CdS)/polysulfide system, where the formation of a PID depends on the color of the illumination. The PID concept thus introduces a new design strategy, where the operating parameters of the solar cell can be manipulated separately. PMID- 26277970 TI - Calculations of Mode-Specific Tunneling of Double-Hydrogen Transfer in Porphycene Agree with and Illuminate Experiment. AB - We report a theoretical study of mode-specific tunneling splittings in double hydrogen transfer in trans-porphycene. We use a novel, mode-specific "Qim path method", in which the reaction coordinate is the imaginary-frequency normal mode of the saddle point separating the equivalent minima. The model considers all 108 normal modes and uses no adjustable parameters. The method gives the ground vibrational-state tunneling splitting, as well the increase in the splitting upon excitation of certain modes, in good agreement with experiment. Interpretation of these results is also transparent with this method. In addition, predictions are made for mode excitations not investigated experimentally. Results for d1 and d2 isotopolgues are also in agreement with experiment. PMID- 26277971 TI - Role of Dispersive Interactions in Determining Structural Properties of Organic Inorganic Halide Perovskites: Insights from First-Principles Calculations. AB - A microscopic picture of structure and bonding in organic-inorganic perovskites is imperative to understanding their remarkable semiconducting and photovoltaic properties. On the basis of a density functional theory treatment that includes both spin-orbit coupling and dispersive interactions, we provide detailed insight into the crystal binding of lead-halide perovskites and quantify the effect of different types of interactions on the structural properties. Our analysis reveals that cohesion in these materials is characterized by a variety of interactions that includes important contributions from both van der Waals interactions among the halide atoms and hydrogen bonding. We also assess the role of spin-orbit coupling and show that it causes slight changes in lead-halide bonding that do not significantly affect the lattice parameters. Our results establish that consideration of dispersive effects is essential for understanding the structure and bonding in organic-inorganic perovskites in general and for providing reliable theoretical predictions of structural parameters in particular. PMID- 26277972 TI - Simultaneous Determination of Structures, Vibrations, and Frontier Orbital Energies from a Self-Consistent Range-Separated Hybrid Functional. AB - A self-consistent optimally tuned range-separated hybrid density functional (scOT RSH) approach is developed. It can simultaneously predict accurate geometries, vibrational modes, and frontier orbital energies. This is achieved by optimizing the range-separation parameter, gamma, to both satisfy the ionization energy theorem and minimize interatomic forces. We benchmark our approach against an established hybrid functional, B3LYP, using the G2 test set. scOT-RSH greatly improves the accuracy of occupied frontier orbital energies, with a mean absolute error (MAE) of only 0.2 eV relative to experimental ionization energies compared to 2.96 eV with B3LYP. Geometries do not change significantly compared to those obtained from B3LYP, with a bond length MAE of 0.012 A compared to 0.008 A for B3LYP, and a 6.5% MAE for zero-point energies, slightly larger than that of B3LYP (3.1%). scOT-RSH represents a new paradigm in which accurate geometries and ionization energies can be predicted simultaneously from a single functional approach. PMID- 26277973 TI - The Impact of Polydispersity and Molecular Weight on the Order-Disorder Transition in Poly(3-hexylthiophene). AB - Conjugated poly(3-hexylthiophene) (P3HT) chains are known to exist at least in two distinct conformations: a coiled phase and a better ordered aggregated phase. Employing steady state absorption and fluorescence spectroscopy, we measure the course of aggregation of P3HT in tetrahydrofuran (THF) solution within a temperature range of 300 K to 170 K. We show that aggregation is a temperature controlled process, driven by a thermodynamic order-disorder transition. The transition temperature increases with the molecular weight of the chains and can be rationalized in the theory of Sanchez. This implies a smearing out of the phase transition in samples with increasing polydispersity and erodes the signature of a first order phase transition. The detection of a hysteresis when undergoing cooling/heating cycles further substantiates this reasoning. PMID- 26277974 TI - Interference and Molecular Transport-A Dynamical View: Time-Dependent Analysis of Disubstituted Benzenes. AB - The primary issue in molecular electronics is measuring and understanding how electrons travel through a single molecule strung between two electrodes. A key area involves electronic interference that occurs when electrons can follow more than one pathway through the molecular entity. When the phases developed along parallel pathways are inequivalent, interference effects can substantially reduce overall conductance. This fundamentally interesting issue can be understood using classical rules of physical organic chemistry, and the subject has been examined broadly. However, there has been little dynamical study of such interference effects. Here, we use the simplest electronic structure model to examine the coherent time-dependent transport through meta- and para-linked benzene circuits, and the effects of decoherence. We find that the phase-caused coherence/decoherence behavior is established very quickly (femtoseconds), that the localized dephasing at any site reduces the destructive interference of the meta-linked species (raising the conductance), and that thermal effects are essentially ineffectual for removing coherence effects. PMID- 26277975 TI - Atomic-Scale Perspective of Ultrafast Charge Transfer at a Dye-Semiconductor Interface. AB - Understanding interfacial charge-transfer processes on the atomic level is crucial to support the rational design of energy-challenge relevant systems such as solar cells, batteries, and photocatalysts. A femtosecond time-resolved core level photoelectron spectroscopy study is performed that probes the electronic structure of the interface between ruthenium-based N3 dye molecules and ZnO nanocrystals within the first picosecond after photoexcitation and from the unique perspective of the Ru reporter atom at the center of the dye. A transient chemical shift of the Ru 3d inner-shell photolines by (2.3 +/- 0.2) eV to higher binding energies is observed 500 fs after photoexcitation of the dye. The experimental results are interpreted with the aid of ab initio calculations using constrained density functional theory. Strong indications for the formation of an interfacial charge-transfer state are presented, providing direct insight into a transient electronic configuration that may limit the efficiency of photoinduced free charge-carrier generation. PMID- 26277976 TI - New Method for Double-Resonance Spectroscopy in a Cold Quadrupole Ion Trap and Its Application to UV-UV Hole-Burning Spectroscopy of Protonated Adenine Dimer. AB - A novel method for double-resonance spectroscopy in a cold quadrupole ion trap is presented, which utilizes dipolar resonant excitation of fragment ions in the quadrupole ion trap. Photofragments by a burn laser are removed by applying an auxiliary RF to the trap, and a probe laser detects the depletion of photofragments by the burn laser. By scanning the wavelength of the burn laser, conformation-specific UV spectrum of a cold ion is obtained. This simple and powerful method is applicable to any type of double-resonance spectroscopy in a cold quadrupole ion trap and was applied to UV-UV hole-burning spectroscopy of protonated adenine dimer. It was found that protonated adenine dimer has multiple conformers/tautomers, each with multiple excited states with drastically different excited state dynamics. PMID- 26277977 TI - Correction to "Inapplicability of Electron-Hopping Models for the Organic Semiconductor Phenyl-C61-butyric Acid Methyl Ester (PCBM)". PMID- 26277979 TI - Diplopia and Ptosis as the Initial Manifestations of Acquired Hepatocerebral Degeneration. PMID- 26277980 TI - Do the Eyes Reveal More Than Scleral Icterus in Sickle Cell Disease? PMID- 26277981 TI - Knockdown of microtubule actin crosslinking factor 1 inhibits cell proliferation in MC3T3-E1 osteoblastic cells. AB - Microtubule actin crosslinking factor 1 (MACF1), a widely expressed cytoskeletal linker, plays important roles in various cells by regulating cytoskeleton dynamics. However, its role in osteoblastic cells is not well understood. Based on our previous findings that the association of MACF1 with F-actin and microtubules in osteoblast-like cells was altered under magnetic force conditions, here, by adopting a stable MACF1-knockdown MC3T3-E1 osteoblastic cell line, we found that MACF1 knockdown induced large cells with a binuclear/multinuclear structure. Further, immunofluorescence staining showed disorganization of F-actin and microtubules in MACF1-knockdown cells. Cell counting revealed significant decrease of cell proliferation and cell cycle analysis showed an S phase cell cycle arrest in MACF1-knockdown cells. Moreover and interestingly, MACF1 knockdown showed a potential effect on cellular MTT reduction activity and mitochondrial content, suggesting an impact on cellular metabolic activity. These results together indicate an important role of MACF1 in regulating osteoblastic cell morphology and function. PMID- 26277982 TI - 2,3-Dimethoxy-2'-hydroxychalcone ameliorates TNF-alpha-induced ICAM-1 expression and subsequent monocyte adhesiveness via NF-kappaB inhibition and HO-1 induction in HaCaT cells. AB - Up-regulation of adhesion molecules plays an important role in the infiltration of leukocytes into the skin during the development of various inflammatory skin diseases, such as atopic dermatitis. In this study, we investigated the modulatory effects of 2,3-dimethoxy-2'-hydroxychalcone (DMHC) on tumor necrosis factor (TNF)-alpha-induced intercellular adhesion molecule-1 (ICAM-1) expression and monocyte adhesiveness, as well as the molecular mechanisms underlying its action in the HaCaT human keratinocyte cell line. Pre-treating HaCaT cells with DMHC significantly suppressed TNF-alpha-induced ICAM-1 expression and subsequent monocyte adhesiveness. DMHC inhibited TNF-alpha-induced activation of NF-kappaB. In addition, DMHC induced HO-1 expression as well as NRF2 activation. Furthermore, HO-1 knockdown using siRNA reversed the inhibitory effect of DMHC on TNF-alpha-induced ICAM-1 expression and adhesion of monocytes to keratinocytes. These results suggest that DMHC may inhibit TNF-alpha-induced ICAM-1 expression and adhesion of monocytes to keratinocytes by suppressing the signaling cascades leading to NF-kappaB activation and inducing HO-1 expression in keratinocytes. PMID- 26277983 TI - Midline enhancer activity of the short gastrulation shadow enhancer is characterized by three unusual features for cis-regulatory DNA. AB - The shadow enhancer of the short gastrulation (sog) gene directs its sequential expression in the neurogenic ectoderm and the ventral midline of the developing Drosophila embryo. Here, we characterize three unusual features of the shadow enhancer midline activity. First, the minimal regions for the two different enhancer activities exhibit high overlap within the shadow enhancer, meaning that one developmental enhancer possesses dual enhancer activities. Second, the midline enhancer activity relies on five Single-minded (Sim)-binding sites, two of which have not been found in any Sim target enhancers. Finally, two linked Dorsal (Dl)- and Zelda (Zld)-binding sites, critical for the neurogenic ectoderm enhancer activity, are also required for the midline enhancer activity. These results suggest that early activation by Dl and Zld may facilitate late activation via the noncanonical sites occupied by Sim. We discuss a model for Zld as a pioneer factor and speculate its role in midline enhancer activity. PMID- 26277984 TI - Independent Predictors of Major Adverse Events following Coronary Stenting over 28 Months of Follow-Up. AB - BACKGROUND: Despite recent advances in stent design and constantly improving protective pharmacological strategies, complications and adverse events following percutaneous coronary interventions (PCI) are still major factors influencing morbidity and mortality. Therefore, predicting secondary vascular occlusions represents an unmet medical need. OBJECTIVE: The aim of our study was to triage clinical and laboratory predictors of major adverse clinical events (MACE) following coronary stenting. METHODS: This was a prospective, case-controlled, single-center study, which included 94 consecutive patients with documented coronary disease who underwent PCI with drug-eluting stent (DES) implantation. All patients received dual antiplatelet therapy with aspirin and clopidogrel. Numerous clinical characteristics and laboratory biomarkers were assessed before stenting and were correlated with poststenting MACE over the mean follow-up of 28 months. MACE included death, nonfatal myocardial infarction, target vessel revascularisation, stroke, stent thrombosis, angina recurrence and instent restenosis. RESULTS: Twenty-three patients experienced MACE. Independent MACE predictors after PCI with DES implantation were antecedent diabetes mellitus (RR = 0.45; 95% CI 0.20-0.97; p = 0.045), prior thrombolytic therapy (RR = 0.42; 95% CI 0.27-0.83; p = 0.039), baseline plasminogen activator inhibitor -1 (PAI-1; p = 0.008) and plasma von Willebrand factor (vWF) activity (p = 0.007). Other clinical characteristics and laboratory indices showed no correlation with MACE. CONCLUSIONS: Background diabetes mellitus, prior thrombolytic therapy, PAI-1 and vWF prestenting activity may be useful for MACE prediction over 28 months of follow-up. PMID- 26277986 TI - Mining of luxS genes from rumen microbial consortia by metagenomic and metatranscriptomic approaches. AB - Although rumen bacterial communities vary depending on many factors such as diet, age and physiological conditions, a core microbiota exists within the rumen. In many natural environments, some bacteria use a quorum-sensing (QS) system to regulate their physiological activities. However, very limited information is available about QS systems in rumen. To investigate the autoinducer 2 (AI-2) mediated QS system in rumen, we detected genes (luxS) encoding the AI-2 synthase (LuxS), from three datasets embedded in metagenomics RAST server (MG-RAST) and from a metatranscriptome dataset. We collected 135 luxS genes from the metagenomic datasets, which were presumed to originate from Bacteroidetes, Firmicutes, Fusobacteria and Actinobacteria, and 34 luxS genes from the metatranscriptome dataset, which probably originated from Bacteroidetes, Firmicutes and Spirochaetes. Because the essential amino acids for LuxS activity were conserved in the LuxS homologues predicted from luxS gene sequences from both datasets, the LuxS homologues probably function in the rumen. Since the largest number of sequences of luxS genes were collected from the genera Prevotella, Ruminococcus and Eubacterium, which include many fibrolytic bacteria and constituent members of biofilm on feed particles, an AI-2-mediated QS system is likely involved in biofilm formation and fibrolytic activity in the rumen. PMID- 26277985 TI - Glutamate cycling may drive organic anion transport on the basal membrane of human placental syncytiotrophoblast. AB - The organic anion transporter OAT4 (SLC22A11) and organic anion transporting polypeptide OATP2B1 (SLCO2B1) are expressed in the basal membrane of the placental syncytiotrophoblast. These transporters mediate exchange whereby uptake of one organic anion is coupled to efflux of a counter-ion. In placenta, these exchangers mediate placental uptake of substrates for oestrogen synthesis as well as clearing waste products and xenobiotics from the fetal circulation. However, the identity of the counter-ion driving this transport in the placenta, and in other tissues, is unclear. While glutamate is not a known OAT4 or OATP2B1 substrate, we propose that its high intracellular concentration has the potential to drive accumulation of substrates from the fetal circulation. In the isolated perfused placenta, glutamate exchange was observed between the placenta and the fetal circulation. This exchange could not be explained by known glutamate exchangers. However, glutamate efflux was trans-stimulated by an OAT4 and OATP2B1 substrate (bromosulphothalein). Exchange of glutamate for bromosulphothalein was only observed when glutamate reuptake was inhibited (by addition of aspartate). To determine if OAT4 and/or OATP2B1 mediate glutamate exchange, uptake and efflux of glutamate were investigated in Xenopus laevis oocytes. Our data demonstrate that in Xenopus oocytes expressing either OAT4 or OATP2B1 efflux of intracellular [(14)C]glutamate could be stimulated by conditions including extracellular glutamate (OAT4), estrone-sulphate and bromosulphothalein (both OAT4 and OATP2B1) or pravastatin (OATP2B1). Cycling of glutamate across the placenta involving efflux via OAT4 and OATP2B1 and subsequent reuptake will drive placental uptake of organic anions from the fetal circulation. PMID- 26277987 TI - Risk of cardiac disease and observations on lack of potential predictors by clinical history among children presenting for cardiac evaluation of mid exertional syncope. AB - OBJECTIVE: This study aimed to evaluate the incidence of cardiac disorders among children with mid-exertional syncope evaluated by a paediatric cardiologist, determine how often a diagnosis was not established, and define potential predictors to differentiate cardiac from non-cardiac causes. Study design We carried out a single-centre, retrospective review of children who presented for cardiac evaluation due to a history of exertional syncope between 1999 and 2012. Inclusion criteria included the following: (1) age ?18 years; (2) mid-exertional syncope; (3) electrocardiogram, echocardiogram and an exercise stress test, electrophysiology study, or tilt test, with exception of long QT, which did not require additional testing; and (4) evaluation by a paediatric cardiologist. Mid exertional syncope was defined as loss of consciousness in the midst of active physical activity. Patients with peri-exertional syncope immediately surrounding but not during active physical exertion were excluded. RESULTS: A total of 60 patients met the criteria for mid-exertional syncope; 32 (53%) were diagnosed with cardiac syncope and 28 with non-cardiac syncope. A majority of cardiac patients were diagnosed with an electrical myopathy, the most common being Long QT syndrome. In nearly half of the patients, a diagnosis could not be established or syncope was felt to be vasovagal in nature. Neither the type of exertional activity nor the symptoms or lack of symptoms occurring before, immediately preceding, and after the syncopal event differentiated those with or without a cardiac diagnosis. CONCLUSIONS: Children with mid-exertional syncope are at risk for cardiac disease and warrant evaluation. Reported symptoms may not differentiate benign causes from life-threatening disease. PMID- 26277988 TI - Quantification of light attenuation in optically cleared mouse brains. AB - Optical clearing, in combination with recently developed optical imaging techniques, enables visualization and acquisition of high-resolution, three dimensional images of biological structures deep within the tissue. Many different approaches can be used to reduce light absorption and scattering within the tissue, but there is a paucity of research on the quantification of clearing efficacy. With the use of a custom-made spectroscopy system, we developed a way to quantify the quality of clearing in biological tissue and applied it to the mouse brain. Three clearing techniques were compared: BABB (1:2 mixture of benzyl alcohol and benzyl benzoate, also known as Murray's clear), pBABB (peroxide BABB, a modification of BABB which includes the use of hydrogen peroxide), and passive CLARITY. We found that BABB and pBABB produced the highest degree of optical clearing. Furthermore, the approach allows regional measurement of light attenuation to be performed, and our results show that light is most attenuated in regions with high lipid content. We provide a way to choose between the multiple clearing protocols available, and it could prove useful for evaluating images that are acquired with cleared tissues. PMID- 26277989 TI - On the interpretation of second harmonic generation intensity profiles of striated muscle. AB - Recently, a supramolecular model was developed for predicting striated skeletal muscle intensity profiles obtained by label-free second harmonic generation (SHG) microscopy. This model allows for a quantitative determination of the length of the thick filament antiparallel range or M-band (M ), and results in M=0.12 MUm for single-band intensity profiles when fixing the A-band length (A ) to A=1.6 MUm , a value originating from electron microscopy (EM) observations. Using simulations and experimental data sets, we showed that the objective numerical aperture (NA) and the refractive index (RI) mismatch (Deltan=n 2omega -n omega ) between the illumination wave (omega ) and the second harmonic wave (2omega ) severely affect the simulated sarcomere intensity profiles. Therefore, our recovered filament lengths did not match with those observed by EM. For an RI mismatch of Deltan=0.02 and a moderate illumination NA of 0.8, analysis of single band SHG intensity profiles with freely adjustable A- and M-band sizes yielded A=1.40+/-0.04 MUm and M=0.07+/-0.05 MUm for skeletal muscle. These lower than expected values were rationalized in terms of the myosin density distribution along the myosin thick filament axis. Our data provided new and practical insights for the application of the supramolecular model to study SHG intensity profiles in striated muscl PMID- 26277990 TI - Maxillary gap at 11-13 weeks' gestation: marker of cleft lip and palate. AB - OBJECTIVE: To describe a new sign of cleft lip and palate (CLP), the maxillary gap, which is visible in the mid-sagittal plane of the fetal face used routinely for measurement of nuchal translucency thickness. METHODS: This was a retrospective study of stored images of the mid-sagittal view of the fetal face at 11-13 weeks' gestation in 86 cases of CLP and 86 normal controls. The images were examined to determine if a maxillary gap was present, in which case its size was measured. RESULTS: In 37 (43.0%) cases of CLP the defect was isolated and in 49 (57.0%) there were additional fetal defects. In the isolated CLP group, the diagnosis of facial cleft was made in the first trimester in nine (24.3%) cases and in the second trimester in 28 (75.7%). In the group with additional defects, the diagnosis of facial cleft was made in the first trimester in 46 (93.9%) cases and in the second trimester in three (6.1%). A maxillary gap was observed in 96% of cases of CLP with additional defects, in 65% of those with isolated CLP and in 7% of normal fetuses. There was a large gap (>1.5 mm) or complete absence of signals from the maxilla in the midline in 69% of cases of CLP with additional defects, in 35% of those with isolated CLP and in none of the normal controls. CONCLUSIONS: The maxillary gap is a new simple marker of possible CLP, which could increase the detection rate of CLP, especially in isolated cases. PMID- 26277991 TI - Development of the Fibronectin-Mimetic Peptide KSSPHSRN(SG)5RGDSP as a Novel Radioprobe for Molecular Imaging of the Cancer Biomarker alpha5beta1 Integrin. AB - alpha5beta1 Integrin, a fibronectin receptor, is becoming a pertinent therapeutic target and a promising prognostic biomarker for cancer patients. The aim of this study was to functionalize an alpha5beta1-specific fibronectin-mimetic peptide sequence KSSPHSRN(SG)5RGDSP (called PR_b) as a positron emission tomography (PET) probe. PR_b was modified by addition of a beta-alanine residue, conjugated with 2 S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn NOTA), and radiolabeled with (18)F based on the chelation of (18)F-aluminum fluoride. A control probe was produced by glycine to alanine substitution in the RGD motif of PR_b. Cell binding and blocking assays, autoradiographic evaluation of tissue binding and blocking, dynamic PET scans, and a biodistribution study were conducted using cell lines and murine tumor models with determined expression levels of alpha5beta1 and other related integrins. (18)F-PR_b was produced with a labeling yield of 22.3+/-1.9% based on (18)F-F(-), a radiochemical purity of >99%, and a specific activity of 30-70 GBq/umol; it exhibited alpha5beta1-binding activity and specificity in vitro, ex vivo, and in vivo, and had a rapid blood clearance and a predominant renal excretion pathway. In vivo alpha5beta1-positive tumors could be clearly visualized by (18)F-PR_b PET imaging. Both imaging and biodistribution studies suggested higher uptake of (18)F-PR_b in alpha5beta1-positive tumors than in alpha5beta1-negative tumors and higher alpha5beta1-positive tumor uptake of (18)F-PR_b than the control probe. In contrast, there was no significant difference seen in the contralateral muscle uptake. A PET radioprobe, (18)F-PR_b, was developed de novo and potentially can be used for noninvasive detection of alpha5beta1 expression in tumors. PMID- 26277992 TI - Unraveling psychomotor slowing in bipolar disorder. AB - BACKGROUND/AIMS: In addition to affective and cognitive symptomatology, psychomotor deficits are known to be present in bipolar disorder (BD). Psychomotor functioning includes all of the processes necessary for completing a movement, from planning to initiation and execution. While these psychomotor symptoms have been studied extensively in schizophrenia and major depressive disorder, only simple measures have been conducted in BD. The present study examines psychomotor functioning in BD. METHODS: Twenty-two euthymic BD patients and 21 healthy controls performed three computerized copying tasks varying in cognitive load. Movement times (MT), reflecting fine motor processing, and initiation times (IT), reflecting cognitive processing of visual-spatial information, were separately measured in each group. RESULTS: The BD patients had longer IT but not MT in the simplest task and the opposite pattern of longer MT but not IT in the complex task. However, when controlling for residual mood symptoms, the MT were no longer significantly slower in the BD group. CONCLUSIONS: The longer MT and IT in BD reflect overall psychomotor slowing. Specifically, the results provide evidence for cognitive slowing in BD. In addition, the longer MT in the complex task reflect a slowed motor component of movement when the cognitive load is high and when depressive symptoms are present. These findings extend the current knowledge of the nature of psychomotor slowing in BD and may have important prognostic implications for patients. PMID- 26277993 TI - Puerarin Protects Human Neuroblastoma SH-SY5Y Cells against Glutamate-Induced Oxidative Stress and Mitochondrial Dysfunction. AB - Glutamate, the principal excitatory neurotransmitter, plays a central role in brain metabolism; however, aberrant neurotransmission of glutamate has been linked to neurodegenerative diseases. Therefore, the effective agents that target at glutamate-induced cell injury will be useful for prevention and treatment of neurodegenerative diseases. In this study, the neuroprotective effect of puerarin, an active isoflavone extracted from the Chinese herb Radix puerariae, against glutamate-induced cell injury in human neuroblastoma SH-SY5Y cells was evaluated for the first time. The results showed that the pretreatment of puerarin could attenuate glutamate-induced cell injury in a dose-dependent manner. This protective effect was mediated through inhibiting reactive oxygen species generation, attenuating the upregulation of Bax and downregulation of Bcl 2, preserving mitochondrial membrane potential (MMP), preventing cytochrome c release, and reducing caspase activity. These findings may significantly contribute to a better understanding of the neuroprotective effect of puerarin and provide new insights into its application toward neurodegenerative diseases in the future. PMID- 26277994 TI - Transparent Stretchable Self-Powered Patchable Sensor Platform with Ultrasensitive Recognition of Human Activities. AB - Monitoring of human activities can provide clinically relevant information pertaining to disease diagnostics, preventive medicine, care for patients with chronic diseases, rehabilitation, and prosthetics. The recognition of strains on human skin, induced by subtle movements of muscles in the internal organs, such as the esophagus and trachea, and the motion of joints, was demonstrated using a self-powered patchable strain sensor platform, composed on multifunctional nanocomposites of low-density silver nanowires with a conductive elastomer of poly(3,4-ethylenedioxythiophene):polystyrenesulfonate/polyurethane, with high sensitivity, stretchability, and optical transparency. The ultra-low-power consumption of the sensor, integrated with both a supercapacitor and a triboelectric nanogenerator into a single transparent stretchable platform based on the same nanocomposites, results in a self-powered monitoring system for skin strain. The capability of the sensor to recognize a wide range of strain on skin has the potential for use in new areas of invisible stretchable electronics for human monitoring. A new type of transparent, stretchable, and ultrasensitive strain sensor based on a AgNW/PEDOT:PSS/PU nanocomposite was developed. The concept of a self-powered patchable sensor system integrated with a supercapacitor and a triboelectric nanogenerator that can be used universally as an autonomous invisible sensor system was used to detect the wide range of strain on human skin. PMID- 26277996 TI - Anti-NMDAR Encephalitis of 11 Cases in China - Detailed Clinical, Laboratory and Imagiological Description. AB - BACKGROUND AND PURPOSE: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a synaptic autoimmune disorder in which the auto-antibodies target NMDARs were first reported in 2007. Now, anti-NMDAR encephalitis is a widely recognized disease in the world. Our purpose was to analyze the clinical characteristics of anti-NMDAR encephalitis patients in West China Hospital in China and report the prognosis of the patients after accepting immunotherapy. METHODS: Patients admitted to the West China Hospital who were diagnosed with anti-NMDAR encephalitis from 2013 to 2014 were retrospectively collected and their clinical features were analyzed. RESULTS: We ultimately included 11 anti-NMDAR encephalitis patients. The median age of the 11 patients was 25 years, 46% patients were females, 27% patients were 15-18 years, and 73% patients were over 18 years. One of them was diagnosed with teratoma after discharging from hospital. The application of immunotherapy produced favorable outcomes in 67% patients included in our study. CONCLUSIONS: Anti-NMDAR encephalitis should be suspected in patients who developed a rapid change in behavior or psychosis, seizures, dyskinesia, and hypoventilation. Anti-NMDAR encephalitis is a kind of fatal but treatable disease. Timely diagnosis and treatment may yield favorable prognosis. PMID- 26277997 TI - Efficient fluorescence energy transfer system between fluorescein isothiocyanate and CdTe quantum dots for the detection of silver ions. AB - We report a fluorescence resonance energy transfer (FRET) system in which the fluorescent donor is fluorescein isothiocyanate (FITC) dye and the fluorescent acceptor is CdTe quantum dot (QDs). Based on FRET quenching theory, we designed a method to detect the concentration of silver ions (Ag(+)). The results revealed a good linear trend over Ag(+) concentrations in the range 0.01-8.96 nmol/L, a range that was larger than with other methods; the quenching coefficient is 0.442. The FRET mechanism and physical mechanisms responsible for dynamic quenching are also discussed. PMID- 26277998 TI - The Effect of Transplacental Administration of Glucagon-Like Peptide-1 on Fetal Lung Development in the Rabbit Model of Congenital Diaphragmatic Hernia. AB - OBJECTIVE: Glucagon-like peptide-1 (GLP-1) increases surfactant protein expression in type 2 pneumocytes. Herein, we determine if transplacental GLP-1 treatment accelerates lung growth in the fetal rabbit model of congenital diaphragmatic hernia (DH). METHODS: Time-mated does had an induction of DH on day 23 followed by daily GLP-1 or placebo injection until term. At that time, the does were weighed, fetal blood was obtained for GLP-1 assay, and the lungs were dissected. Fetal outcome measures were lung-to-body-weight ratio (LBWR), morphometry, and Ki67 and surfactant protein B (SPB) expression. RESULTS: Maternal weight loss in the GLP-1 group was 7.1%. Fetal survival was lower in GLP 1 fetuses compared to placebo controls (27/85, 32% vs. 35/57, 61%; p < 0.05). Fetal GLP-1 levels were increased 3.6-fold. The LBWR of GLP-1 DH fetuses fell within the range of DH placebo fetuses (1.166 +/- 0.207% vs. 1.312 +/- 0.418%), being significantly lower than that of placebo-exposed unoperated fetuses (2.280 +/- 0.522%; p < 0.001). GLP-1 did not improve airway morphometry. GLP-1 DH lungs had a reduced adventitial and medial thickness within the range of controls, and lesser muscularization of vessels measuring 30-60 um. There were no differences in Ki67 and SPB expression. CONCLUSION: GLP-1 at this dosage improves peripheric pulmonary vessel morphology in intra-acinar vessels with no effect on airway morphometry but with significant maternal and fetal side effects. Thus, it is an unlikely medical strategy. PMID- 26277999 TI - Evidence-based medicine and acupuncture: old bias for new perspectives in clinical context. PMID- 26278000 TI - Clinical Methodology Matters in Epidemiology: Not All Benzodiazepines Are the Same. PMID- 26278001 TI - P-Wave Dispersion and Atrial Electromechanical Delay in Patients with Preeclampsia. AB - OBJECTIVES: To investigate the duration of atrial electromechanical delay (EMD) and left atrial mechanical function in patients with preeclampsia. MATERIALS AND METHODS: This study included 26 pregnant women with preeclampsia and 24 age matched pregnant women without preeclampsia (control group). Atrial electromechanical coupling (PA) and intra-atrial and interatrial EMD were measured using tissue Doppler echocardiography. P-wave dispersion (PWD) was measured via 12-lead electrocardiography. All data were analyzed using SPSS v.15.0 for Windows (SPSS, Inc., Chicago, Ill., USA). Differences in continuous variables between groups were examined using a nonparametric Mann-Whitney U test. Correlation analysis was performed using Spearman's coefficient of correlation. Categorical values were compared using a chi2 test. RESULTS: PA lateral and PA septal durations were significantly longer in the preeclampsia group than in the control group [74.6 +/- 8.1 vs. 62.3 +/- 5.3 ms (p < 0.001) and 59.7 +/- 5.3 vs. 56.2 +/- 4.9 ms (p = 0.005), respectively]. The duration of interatrial EMD and intra-atrial EMD in the preeclampsia group was significantly longer than in the control group [25.4 +/- 4.6 vs. 13.2 +/- 3.9 ms (p < 0.001) and 10.5 +/- 1.9 vs. 7.1 +/- 1.2 ms (p < 0.001), respectively]. PWD was significantly higher in patients with preeclampsia (43.1 +/- 9.1 ms) than in the controls (37.6 +/- 7.9 ms; p = 0.008). There was a significant correlation between PWD and interatrial EMD and intra-atrial EMD [r = 0.46 (p < 0.001) and r = 0.39 (p < 0.001), respectively]. CONCLUSION: The duration of atrial EMD and PWD was prolonged in patients with preeclampsia. PMID- 26278002 TI - Adapting an evidence-based intervention for HIV to avail access to testing and risk-reduction counseling for female victims of sexual violence in post earthquake Haiti. AB - Haiti has the highest prevalence of HIV/AIDS in the Caribbean. Before the 2010 earthquake, Haitian women bore a disproportionate burden of HIV/AIDS, had lower HIV knowledge, less capacity to negotiate for safer sex, and limited access to HIV testing and risk-reduction (RR) counseling. Since 2010, there has been an increase in sexual violence against women, characterized by deliberate vaginal injuries by non-intimate partners, increasing victims' risk of sexually transmitted infections including HIV/AIDS. Needed is an adaptation of evidence based interventions for HIV that include HIV testing and counseling for this stigmatized population. We reviewed several features of Centers for Disease Control and Prevention's 103 evidence-based interventions for HIV (e.g., measures used, participant risk characteristics, theoretical framework, outcome variables, and evidence tier) in an attempt to seek a feasibly adaptable evidence-based intervention for HIV that could be used for victims of sexual violence (VOSV). RESPECT, one of the reviewed evidence-based HIV interventions, comprises of one on-one, client-focused HIV prevention/RR counseling, and RAPID HIV testing. Adapting RESPECT can enhance access to testing for Haitian VOSV and can influence their perceptions of HIV risk, and establishment of RR goals for future consensual intimate relations. Adapting and implementing RESPECT can increase uptake of evidence-based HIV interventions among Haitians and positively affect a region with high HIV prevalence and increased rates of sexual violence. PMID- 26278003 TI - Generational increase in obesity among young women: a prospective analysis of mother-daughter dyads. AB - BACKGROUND/OBJECTIVES: Increases in obesity in young adults over recent decades are shown by national survey data but have yet to be replicated using prospective data. We aim to quantify the increase in obesity and overweight over two generations of young adult women using prospective measures of body mass index (BMI). SUBJECTS/METHODS: Data are from the Mater University Study of Pregnancy (MUSP), a prospective pre-birth cohort study started in 1981 in Brisbane, Australia. Analyses were restricted to 992 mother-daughter dyads who were at similar ages at the time they were assessed and for whom measures of BMI were available. We also conducted an additional analysis to test whether there was a similar increase amongst father-son dyads. We used multinomial logistic regression for clustered data to compare the same prospective measures of BMI categories between mother and daughters. RESULTS: Controlling for a number of sociodemographic and lifestyle factors in the female sample, daughters had 5.04 (3.03, 8.85) times the odds of being obese and 2.54 (1.86, 3.54) times the odds of being overweight compared with their mothers. A large increase in obesity was also observed in the male sample. CONCLUSIONS: Using a longitudinal design to partly account for familial confounding of obesity risk factors, this study confirms a large and concerning increases in obesity rates over two generations of young adults and suggests increases in obesity over the past 20 years may be greater than previously anticipated. PMID- 26278004 TI - Modelling the associations between fat-free mass, resting metabolic rate and energy intake in the context of total energy balance. AB - BACKGROUND: The relationship between body composition, energy expenditure and ad libitum energy intake (EI) has rarely been examined under conditions that allow any interplay between these variables to be disclosed. OBJECTIVE: The present study examined the relationships between body composition, energy expenditure and EI under controlled laboratory conditions in which the energy density and macronutrient content of the diet varied freely as a function of food choice. METHODS: Fifty-nine subjects (30 men: mean body mass index=26.7+/-4.0 kg m(-2); 29 women: mean body mass index=25.4+/-3.5 kg m(-)(2)) completed a 14-day stay in a residential feeding behaviour suite. During days 1 and 2, subjects consumed a fixed diet designed to maintain energy balance. On days 3-14, food intake was covertly measured in subjects who had ad libitum access to a wide variety of foods typical of their normal diets. Resting metabolic rate (RMR; respiratory exchange), total daily energy expenditure (doubly labelled water) and body composition (total body water estimated from deuterium dilution) were measured on days 3-14. RESULTS: Hierarchical multiple regression indicated that after controlling for age and sex, both fat-free mass (FFM; P<0.001) and RMR (P<0.001) predicted daily EI. However, a mediation model using path analysis indicated that the effect of FFM (and fat mass) on EI was fully mediated by RMR (P<0.001). CONCLUSIONS: These data indicate that RMR is a strong determinant of EI under controlled laboratory conditions where food choice is allowed to freely vary and subjects are close to energy balance. Therefore, the conventional adipocentric model of appetite control should be revised to reflect the influence of RMR. PMID- 26278005 TI - Effect of extended morning fasting upon ad libitum lunch intake and associated metabolic and hormonal responses in obese adults. AB - BACKGROUND/OBJECTIVES: Breakfast omission is positively associated with obesity and increased risk of disease. However, little is known about the acute effects of extended morning fasting upon subsequent energy intake and associated metabolic/regulatory factors in obese adults. SUBJECTS/METHODS: In a randomised cross-over design, 24 obese men (n=8) and women (n=16) extended their overnight fast by omitting breakfast consumption or ingesting a typical carbohydrate-rich breakfast of 2183+/-393 kJ (521+/-94 kcal), before an ad libitum pasta lunch 3 h later. Blood samples were obtained throughout the day until 3 h post lunch and analysed for hormones implicated in appetite regulation, along with metabolic outcomes and subjective appetite measures. RESULTS: Lunch intake was unaffected by extended morning fasting (difference=218 kJ, 95% confidence interval -54 kJ, 490 kJ; P=0.1) resulting in lower total intake in the fasting trial (difference= 1964 kJ, 95% confidence interval -1645 kJ, -2281 kJ; P<0.01). Systemic concentrations of peptide tyrosine-tyrosine and leptin were lower during the afternoon following morning fasting (P?0.06). Plasma-acylated ghrelin concentrations were also lower following the ad libitum lunch in the fasting trial (P<0.05) but this effect was not apparent for total ghrelin (P?0.1). Serum insulin concentrations were greater throughout the afternoon in the fasting trial (P=0.05), with plasma glucose also greater 1 h after lunch (P<0.01). Extended morning fasting did not result in greater appetite ratings after lunch, with some tendency for lower appetite 3 h post lunch (P=0.09). CONCLUSIONS: We demonstrate for the first time that, in obese adults, extended morning fasting does not cause compensatory intake during an ad libitum lunch nor does it increase appetite during the afternoon. Morning fasting reduced satiety hormone responses to a subsequent lunch meal but counterintuitively also reduced concentrations of the appetite-stimulating hormone-acylated ghrelin during the afternoon relative to lunch consumed after breakfast. PMID- 26278007 TI - Single-photon decision maker. AB - Decision making is critical in our daily lives and for society in general and is finding evermore practical applications in information and communication technologies. Herein, we demonstrate experimentally that single photons can be used to make decisions in uncertain, dynamically changing environments. Using a nitrogen-vacancy in a nanodiamond as a single-photon source, we demonstrate the decision-making capability by solving the multi-armed bandit problem. This capability is directly and immediately associated with single-photon detection in the proposed architecture, leading to adequate and adaptive autonomous decision making. This study makes it possible to create systems that benefit from the quantum nature of light to perform practical and vital intelligent functions. PMID- 26278006 TI - A novel interaction between the FLJ33534 locus and smoking in obesity: a genome wide study of 14 131 Pakistani adults. AB - BACKGROUND: Obesity is a complex disease caused by the interplay of genetic and lifestyle factors, but identification of gene-lifestyle interactions in obesity has remained challenging. Few large-scale studies have reported use of genome wide approaches to investigate gene-lifestyle interactions in obesity. METHODS: In the Pakistan Risk of Myocardial Infraction Study, a cross-sectional study based in Pakistan, we calculated body mass index (BMI) variance estimates (square of the residual of inverse-normal transformed BMI z-score) in 14 131 participants and conducted genome-wide heterogeneity of variance analyses (GWHVA) for this outcome. All analyses were adjusted for age, age(2), sex and genetic ancestry. RESULTS: The GWHVA analyses identified an intronic variant, rs140133294, in the FLJ33544 gene in association with BMI variance (P-value=3.1 * 10(-8)). In explicit tests of gene * lifestyle interaction, smoking was found to significantly modify the effect of rs140133294 on BMI (Pinteraction=0.0005), whereby the minor allele (T) was associated with lower BMI in current smokers, while positively associated with BMI in never smokers. Analyses of ENCODE data at the FLJ33534 locus revealed features indicative of open chromatin and high confidence DNA-binding motifs for several transcription factors, providing suggestive biological support for a mechanism of interaction. CONCLUSIONS: In summary, we have identified a novel interaction between smoking and variation at the FLJ33534 locus in relation to BMI in people from Pakistan. PMID- 26278008 TI - An improved cucumber mosaic virus-based vector for efficient decoying of plant microRNAs. AB - We previously devised a cucumber mosaic virus (CMV)-based vector system carrying microRNA target mimic sequences for analysis of microRNA function in Arabidopsis thaliana. We describe an improved version in which target mimic cloning is achieved by annealing two partly-overlapping complementary DNA oligonucleotides for insertion into an infectious clone of CMV RNA3 (LS strain) fused to the cauliflower mosaic virus-derived 35S promoter. LS-CMV variants carrying mimic sequences were generated by co-infiltrating plants with Agrobacterium tumefaciens cells harboring engineered RNA3 with cells carrying RNA1 and RNA2 infectious clones. The utility of using agroinfection to deliver LS-CMV-derived microRNA target mimic sequences was demonstrated using a miR165/166 target mimic and three solanaceous hosts: Nicotiana benthamiana, tobacco (N. tabacum), and tomato (Solanum lycopersicum). In all three hosts the miR165/166 target mimic induced marked changes in developmental phenotype. Inhibition of miRNA accumulation and increased target mRNA (HD-ZIP III) accumulation was demonstrated in tomato. Thus, a CMV-derived target mimic delivered via agroinfection is a simple, cheap and powerful means of launching virus-based miRNA mimics and is likely to be useful for high-throughput investigation of miRNA function in a wide range of plants. PMID- 26278009 TI - The ubiquity and ancestry of insect doublesex. AB - The doublesex (dsx) gene functions as a molecular switch at the base of the insect sex determination cascade, and triggers male or female somatic sexual differentiation in Drosophila. Having been reported from only seven current insect orders, the exact phylogenetic distribution of dsx within the largest Arthropod sub-phylum, the Hexapoda, is unknown. To understand the evolution of this integral gene relative to other arthropods, we tested for the presence of dsx within public EST and genome sequencing projects representative of all 32 hexapod orders. We find the dsx gene to be ubiquitous, with putative orthologs recovered from 30 orders. Additionally, we recovered both alternatively spliced and putative paralogous dsx transcripts from several orders of hexapods, including basal lineages, indicating the likely presence of these characteristics in the hexapod common ancestor. Of note, other arthropods such as chelicerates and crustaceans express two dsx genes, both of which are shown to lack alternative splicing. Furthermore, we discovered a large degree of length heterogeneity in the common region of dsx coding sequences within and among orders, possibly resulting from lineage-specific selective pressures inherent to each taxon. Our work serves as a valuable resource for understanding the evolution of sex determination in insects. PMID- 26278010 TI - Junction formation and current transport mechanisms in hybrid n-Si/PEDOT:PSS solar cells. AB - We investigated hybrid inorganic-organic solar cells combining monocrystalline n type silicon (n-Si) and a highly conductive polymer poly(3,4 ethylenedioxythiophene)-poly(styrene sulfonate) ( PEDOT: PSS). The build-in potential, photo- and dark saturation current at this hybrid interface are monitored for varying n-Si doping concentrations. We corroborate that a high build-in potential forms at the hybrid junction leading to strong inversion of the n-Si surface. By extracting work function and valence band edge of the polymer from ultraviolet photoelectron spectroscopy, a band diagram of the hybrid n-Si/ PEDOT: PSS heterojunction is presented. The current-voltage characteristics were analyzed using Schottky and abrupt pn-junction models. The magnitude as well as the dependence of dark saturation current on n-Si doping concentration proves that the transport is governed by diffusion of minority charge carriers in the n Si and not by thermionic emission of majorities over a Schottky barrier. This leads to a comprehensive explanation of the high observed open-circuit voltages of up to 634 mV connected to high conversion efficiency of almost 14%, even for simple planar device structures without antireflection coating or optimized contacts. The presented work clearly shows that PEDOT: PSS forms a hybrid heterojunction with n-Si behaving similar to a conventional pn-junction and not, like commonly assumed, a Schottky junction. PMID- 26278011 TI - Variants in the Regulatory Region of WNT5A Reduced Risk of Cardiac Conotruncal Malformations in the Chinese Population. AB - WNT5A is one of the most highly investigated non-canonical Wnt ligands and is involved in the embryonic heart development, especially in formation of the cardiac conotruncal region by regulating the migration and differentiation of cardiac neural crest (CNC) and second heart field (SHF) cells. No study to date has comprehensively characterized the WNT5A regulatory variants in patients with congenital heart malformations (CHMs). The association between regulatory variants of the WNT5A gene and CHMs was examined in case-control association study in 1,210 CHMs and 798 controls. Individuals carrying a homozygous genotype CC (rs524153) or GG (rs504849) had a similarly reduced risk of conotruncal malformations. The homozygous genotypes (CC for rs524153 and GG for rs504849) were associated with a lower WNT5A transcriptional level compared with the transcriptional level of those with wild-type genotypes. Further functional analysis revealed that an additional upstream single nucleotide polymorphisms (SNP) rs371954924 (-5244GCCA > CC) in a linkage disequilibrium (LD) block with the above genotyped SNPs decreased WNT5A expression through the attenuated binding affinity with the transcription factor SOX9. This is the first demonstration that genetic variants in the regulatory regions of WNT5A play a vital role in sporadic conotruncal malformations susceptibility through the changeable expression of the WNT5A gene. PMID- 26278012 TI - Primary breast leiomyosarcoma located in the premammary zone: a case report. AB - We present the case of 51-year-old woman with a primary breast leiomyosarcoma. On the postoperative screening after breast cancer surgery, a 4-mm-sized mass assessed as BI-RADS category 3 was detected on her contralateral breast. We recommended follow-up and observation. However, the lesion increased in size and became palpable. It was excised and diagnosed as primary leiomyosarcoma. We review the literature on imaging findings and management of breast leiomyosarcoma, and discuss the differential diagnoses in breast imaging. PMID- 26278013 TI - Added value of morphologic characteristics on diffusion-weighted images for characterizing lymph nodes in primary rectal cancer. AB - To evaluate the added value of the morphologic features of lymph nodes (LNs) on diffusion-weighted images (DWI), an interval reading was performed for the T2 weighted images (T2WI) and the combined image set (T2WI and DWI) using extracted imaging characteristics from 54 metastatic and 172 benign LNs in 44 patients with primary rectal cancer. The specificity and accuracy increased after adding DWI to T2WI for both readers (specificity: from 59% to 73% and from 41% to 68% for readers 1 and 2, respectively; accuracy: from 58% to 68% and from 44% to 64% for readers 1 and 2, respectively, P<.0001). PMID- 26278014 TI - Predictors of intrahepatic cholangiocarcinoma in cirrhotic patients scanned by gadobenate dimeglumine-enhanced magnetic resonance imaging: diagnostic accuracy and confidence. AB - OBJECTIVE: To identify predictors of intrahepatic cholangiocarcinoma in cirrhotic patients scanned by gadobenate dimeglumine (Gd-BOPTA)-enhanced magnetic resonance (MR) imaging. METHODS: Fifty cirrhotic patients with 120 nodules, including 10 mass-forming intrahepatic cholangiocarcinomas and two combined hepatocellular carcinoma-cholangiocarcinomas, were scanned by Gd-BOPTA-enhanced MR imaging. RESULTS: T1 hypointensity [odds ratio (OR), 20.12], peripheral hyperintense rim at hepatic arterial phase (OR, 13.5), and iso-hyperintensity at hepatobiliary phase (OR 21.32) were found to be independent predictors of intrahepatic cholangiocarcinoma. CONCLUSIONS: T1 hypointensity, peripheral hyperintense rim at hepatic arterial phase, and iso-hyperintensity at hepatobiliary phase are independent predictors of intrahepatic cholangiocarcinoma diagnosis in patients with liver cirrhosis. PMID- 26278015 TI - Curcumin treatment enhances the effect of exercise on mitochondrial biogenesis in skeletal muscle by increasing cAMP levels. AB - BACKGROUND: In response to physiologic stressors, skeletal muscle has the potential to elicit wide variety of adaptive responses, such as biogenesis of mitochondria and clearance of damaged mitochondria to promote healthy muscle. The polyphenol curcumin, derived from the rhizome Curcuma longa L., is a natural antioxidant that exhibits various pharmacological activities and therapeutic properties. However, the effect of curcumin on the regulation of mitochondrial biogenesis in skeletal muscle remains unknown. The present study aimed to examine the effects of combination of endurance training (eTR) and curcumin treatment on the expression of AMPK, SIRT1, PGC-1alpha, and OXPHOS subunits, mitochondrial DNA copy number, and CS activity in rat skeletal muscle. Furthermore, the present study also examined the effect of exercise and curcumin treatment on the levels of cAMP and downstream targets of PKA including phosphorylated CREB and LKB-1. METHODS: Ten-week-old male Wistar rats were randomly divided into non-eTR and eTR groups. Low doses (50 mg/kg-BW/day) or high doses (100 mg/kg-BW/day) of curcumin dissolved in dimethyl sulfoxide (DMSO) were injected intraperitoneally in all animals for 28 days to investigate the effect of curcumin alone and the combined effect of curcumin with eTR. Western blotting (WB) and immunoprecipitation (IP) were performed to detect the presence of proteins. RESULTS: Our results demonstrated that combination of curcumin treatment and eTR increased the expression of COX-IV, OXPHOS subunits, mitochondrial DNA copy number and CS activity in the gastrocnemius (Gas) and soleus (Sol) muscles. In addition, this combination increased AMPK phosphorylation, NAD(+)/NADH ratio, SIRT1 expression, and PGC-1alpha deacetylation. Furthermore, curcumin treatment as well as exercise also increased levels of cAMP and downstream target of PKA including phosphorylation CREB and LKB-1 which are involved in the regulation of mitochondrial biogenesis. CONCLUSION: Taken together, these results suggest that the combination of curcumin treatment and eTR has the potential to accelerate mitochondrial biogenesis in skeletal muscle by increasing cAMP levels. PMID- 26278016 TI - Synthesis of Fluoroalkoxy Substituted Arylboronic Esters by Iridium-Catalyzed Aromatic C-H Borylation. AB - The preparation of fluoroalkoxy arylboronic esters by iridium-catalyzed aromatic C-H borylation is described. The fluoroalkoxy groups employed include trifluoromethoxy, difluoromethoxy, 1,1,2,2-tetrafluoroethoxy, and 2,2-difluoro 1,3-benzodioxole. The borylation reactions were carried out neat without the use of a glovebox or Schlenk line. The regioselectivities available through the iridium-catalyzed C-H borylation are complementary to those obtained by the electrophilic aromatic substitution reactions of fluoroalkoxy arenes. Fluoroalkoxy arylboronic esters can serve as versatile building blocks. PMID- 26278017 TI - Hyperthermic intraperitoneal chemotherapy with cisplatin: Amifostine prevents acute severe renal impairment. AB - Surgical cytoreduction combined with intraperitoneal chemo-hyperthermia (HIPEC) has shown to provide survival benefits in the management of some peritoneal carcinomatosis. The cisplatin (CP) used in HIPEC carries a risk of renal impairment (RI). This risk could be reduced by administration of amifostine (A). The aim of our study was to assess the utility of A in preventing RI during IPCH with CP. PATIENTS AND METHODS: Retrospective study including patients who underwent HIPEC between January 2007 and June 2013. The HIPEC involved administration of CP and mitomycin C, between 41 and 43 degrees C. The peri anaesthetic management was consistent to use A after 2010. Renal function was assessed from the measured creatinine clearance (CreatCl) and the change between D0 and D4 was compared between patients who received A (group A+) and those who did not (group A-). Severe RI was defined as the development of a CreatCl of <30 ml/min. The statistical analysis used a Student t-test and Fischer's exact test. A p-value of <0.05 was deemed to be statistically significant. RESULTS: Over the studied period, seventy five patients underwent HIPEC and the findings from fifty two patients were analysed: thirty one in group A+ and twenty one in group A-. The change in mean CreatCl from D0 to D4 did not differ between the two groups although between D1 and D4 a significantly higher percentage of severe RI was seen in group A-. CONCLUSIONS: This study has shown A to offer benefit in terms of reducing severe RI when CP is used in HIPEC. These results, however, will need to be confirmed in prospective series on larger numbers of patients. PMID- 26278018 TI - Routes to diagnosis for sarcoma - Describing the sarcoma patient journey. AB - BACKGROUND: Understanding the route to diagnosis for patients with cancer is important to improve the diagnostic pathway and therefore outcomes. We aimed to investigate routes to diagnosis for patients with sarcoma in England. METHODS: National patient level datasets relating to 7716 soft tissue and 1240 bone sarcoma patients diagnosed between 2006 and 2008 were analysed. Routes to diagnosis were defined as: "Two Week Wait Referral", "GP Referral", "Other Outpatient", "Inpatient Elective", "Emergency Presentation", "Death Certificate Only" and "Unknown". RESULTS: Patients with sarcoma are most likely to be diagnosed after "GP Referral" or "Emergency Presentation" and are less likely to be referred under a two week wait compared with other malignancies. Patients with bone sarcoma under 10 or over 80 years of age were more likely to present by emergency routes, as were patients with vertebral column, pelvis or unspecified site tumours and those with Ewing's sarcoma or sarcoma NOS. Patients with soft tissue sarcoma under 19 or over 80 years of age and patients with GI tract tumours were more likely to present by emergency routes. Patients presenting by emergency routes more often had metastases and had lower 1 year survival. Patients from least deprived quintiles more often presented by unknown routes: those from more deprived quintiles more often presented by emergency routes. CONCLUSION: Routes to diagnosis for sarcoma patients differ from other cancers. Interventions to improve the diagnostic experience should consider the very young and elderly, tumours in abdominal, pelvic or spinal locations and on reducing emergency presentations. PMID- 26278020 TI - Gender differences of sagittal knee and ankle biomechanics during stair-to-ground descent transition. AB - BACKGROUND: Falls on stairs often result in severe injury and occur twice as frequently in women. However, gender differences in kinetics and kinematics during stair descent are unknown. Thus, this study aimed to determine whether gender differences of knee and ankle biomechanics exist in the sagittal plane during the stair-to-ground descending transition. It was hypothesized that 1) women would reveal higher ground-toe-trochanter angle and lower ground-toe length during stair-to-ground descent transition than men; and 2) women would reveal lower peak knee extension moment during stair-to-ground descent transition than men. METHODS: Fifteen men and fifteen women were recruited and performed a stair descent activity. Kinetic and kinematic data were obtained using a force plate and motion capture system. FINDINGS: The women performed the stair descent with a lower peak knee extension moment and a peak knee power at the early weight acceptance phase. The women also revealed a higher ground-toe-trochanter angle and a lower ground-toe length, which indicated a more forward position of the lower extremity relative to the toe contact point at both the initial contact and at the time of peak kinematic and kinetic events. INTERPRETATION: This study found that knee and ankle kinematics and kinetics differed significantly between the genders due to differences in ground-toe-trochanter angle. Women have a different stair descending strategy that reduces the demand of the lower extremity muscle function, but this strategy seems to increase the risk of falls. PMID- 26278021 TI - N-glycosylation-mutated HCV envelope glycoprotein complex enhances antigen presenting activity and cellular and neutralizing antibody responses. AB - BACKGROUND: The development of an efficient vaccine and broadly cross neutralizing antibodies of hepatitis C virus (HCV) remains a priority. The heavily glycosylated viral envelope glycoprotein E1E2 complex is a candidate vaccine antigen. Bacteria-derived unmethylated CpG DNA, a potent stimulator of immune cells, is important for vaccine research. METHODS: Here, the immunogenicities of wild type (WT) E1E2, five N-glycosylation site mutated E1E2 glycoproteins, and five CpG-coupled E1E2 N-glycosylation mutated glycoproteins were analyzed in BALB/c mice by DNA vaccination using in vivo electroporation. RESULTS: The E1E2 protein expression levels were examined and shown to be unaffected by these N-glycosylation mutations. We found that a CpG-coupled E1 N209D-E2-N430D DNA vaccine (named CpG-E1E2-M4) induced the highest cellular immune response compared to the WT E1E2, CpG-E1E2, and other mutants. Furthermore, the CpG-E1E2-M4 anti-serum effectively neutralized the infection of cell-cultured HCV (HCVcc, genotype 2a)- and HCV pseudo particles (HCVpp, genotypes 1 to 7) to Huh-7.5.1 hepatocytes. Additionally, CpG-E1E2-M4 enhanced the Interleukin-12 (IL-12) production and antigen-presenting activity of CD11c(+) dendritic cells (DCs) by inducing CD4(+) Th1 polarization and the production of perforin and granzyme B (GrB) in CD8(+) T cells. CONCLUSIONS: As our knowledge this is the first study revealing that the naturally poor immunogenicity of E1E2 can be enhanced by the deletion of N-glycans combined with the addition of immune activator CpG by DNA vaccination. GENERAL SIGNIFICANCE: Deletion of N-glycans can enhance viral immunogenicity. The selected CpG-E1E2-M4 mutant is a novel potential HCV DNA vaccine that elicits enhanced CD4(+) Th1 and CD8(+) T cell responses and neutralizing antibody production against HCV infection. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc. PMID- 26278019 TI - The effect of EUSOMA certification on quality of breast cancer care. AB - AIM OF THE STUDY: The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast units to establish minimum standards and ensure specialist multidisciplinary care. In the present study we assess the impact of EUSOMA certification for all breast units for which sufficient information was available before and after certification. MATERIALS AND METHODS: For 22 EUSOMA certified breast units data of 30,444 patients could be extracted from the EUSOMA database on the evolution of QI's before and after certification. RESULTS: On the average of all units, the minimum standard of care was achieved for 12/13 QI's before and after EUSOMA certification (not met for DCIS receiving just one operation). There was a significant improvement of 5 QI's after certification. The proportion of patients with invasive cancer undergoing an axillary clearance containing >9 lymph nodes (91.5% vs 89.4%, p 0.003) and patients with invasive cancer having just 1 operation (83.1% vs 80.4%, p < 0.001) dropped, but remained above the minimum standard. The targeted standard of breast care was reached for the same 4/13 QI's before and after EUSOMA certification. CONCLUSION: Although the absolute effect of EUSOMA certification was modest it further increases standards of care and should be regarded as part of a process aiming for excellence. Dedicated units already provide a high level of care before certification, but continuous monitoring and audit remains of paramount importance as complete adherence to guidelines is difficult to achieve. PMID- 26278022 TI - Mode of DNA binding with gamma-butyrolactone receptor protein CprB from Streptomyces coelicolor revealed by site-specific fluorescence dynamics. AB - BACKGROUND: The gamma-butyrolactone (GBL) binding transcription factors in Streptomyces species are known for their involvement in quorum sensing where they control the expression of various genes initiating secondary metabolic pathways. The structurally characterized member of this family CprB from Streptomyces coelicolor had earlier been demonstrated to bind a multitude of sequences containing a specific binding signature. Though structural breakthrough has been obtained for its complex with a consensus DNA sequence there is, however a dearth of information regarding the overall and site specific dynamics of protein-DNA interaction. METHODS: To delineate the effect of CprB on the bound DNA, changes in motional dynamics of the fluorescent probe 2-aminopurine were monitored at three conserved base positions (5th, 12th and 23rd) for two DNA sequences: the consensus and the biologically relevant cognate element, on complex formation. RESULTS: The changes in lifetime and generalized order parameter revealed a similarity in the binding pattern of the protein to both sequences with greater dynamic restriction at the end positions, 5th and 23rd, as compared to the middle 12th position. Also differences within this pattern demonstrated the influence of even small changes in sequence on protein interactions. CONCLUSIONS: Here the study of motional dynamics was instrumental in establishing a structural footprint for the cognate DNA sequence and explaining the dynamics for the consensus DNA from structural correspondence. GENERAL SIGNIFICANCE: Motional dynamics can be a powerful tool to efficiently study the mode of DNA binding to proteins that interact differentially with a plethora of DNA sequences, even in the absence of structural breakthrough. PMID- 26278023 TI - A taxonomy of rapid reviews links report types and methods to specific decision making contexts. AB - OBJECTIVES: Describe characteristics of rapid reviews and examine the impact of methodological variations on their reliability and validity. STUDY DESIGN AND SETTING: We conducted a literature review and interviews with organizations that produce rapid reviews or related products to identify methods, guidance, empiric evidence, and current practices. RESULTS: We identified 36 rapid products from 20 organizations (production time, 5 minutes to 8 months). Methods differed from systematic reviews at all stages. As time frames increased, methods became more rigorous; however, restrictions on database searching, inclusion criteria, data extracted, and independent dual review remained. We categorized rapid products based on extent of synthesis. "Inventories" list what evidence is available. "Rapid responses" present best available evidence with no formal synthesis. "Rapid reviews" synthesize the quality of and findings from the evidence. "Automated approaches" generate meta-analyses in response to user-defined queries. Rapid products rely on a close relationship with end users and support specific decisions in an identified time frame. Limited empiric evidence exists comparing rapid and systematic reviews. CONCLUSIONS: Rapid products have tremendous methodological variation; categorization based on time frame or type of synthesis reveals patterns. The similarity across rapid products lies in the close relationship with the end user to meet time-sensitive decision-making needs. PMID- 26278024 TI - Patient's satisfaction after outpatient forefoot surgery: Study of 619 cases. AB - INTRODUCTION: The number of outpatient surgical procedures performed in France on the forefoot has grown rapidly in recent years. OBJECTIVES: The goal of this study was to evaluate experience and satisfaction of patients undergoing outpatient foot surgery using a telephone questionnaire developed for this purpose. MATERIAL AND METHODS: In 2012 and 2013, every patient who was admitted to the day surgery unit at our hospital for an open procedure on their forefoot was called the morning after the procedure. A nurse went through the 14-item questionnaire with the patient. The same perioperative protocol, written instructions and treatment were used for all patients. RESULTS: Six hundred nineteen patients were included. The questionnaire response rate was 89% (n=540). Isolated hallux valgus surgery was performed on 319 patients (61%); 107 patients (20%) underwent hallux valgus surgery with lateral metatarsal osteotomy; 57 patients (10.5%) underwent first metatarsophalangeal fusion and 47 patients (8.5%) underwent a procedure on the lateral rays only. In the postoperative phase, 65% reported having satisfactory sleep quality, 32% had experienced nausea, 16% had experienced vomiting and 17% had experienced bleeding. Eighty percent of patients experienced pain (VAS >= 1); 80% of these patients had their pain relieved by the prescribed treatment and 4% had not taken it. Nearly all the patients (99%) were satisfied with the outpatient care; the overall satisfaction score was 9.4 out of 10. There was a significant relationship between the type of procedure and vomiting, pain, bleeding and fever. DISCUSSION: Outpatient care is becoming more common in response to economic challenges. The development of outpatient foot surgery appears to have satisfied the vast majority of operated patients. However, adjustments should be made to improve their tolerance to the pain management protocol. Although the logistics of performing follow-up call can be complicated, the patients appreciate receiving this call the next day. The call also seems to reassure both the patients and care providers. PMID- 26278025 TI - Breath hydrogen and methane are associated with intestinal symptoms in patients with chronic pancreatitis. AB - BACKGROUNDS: The bacterial overgrowth might be associated with chronic pancreatitis. This study was to evaluate the prevalence and characteristics of small intestinal bacterial overgrowth (SIBO) in patients with chronic pancreatitis. METHODS: 36 patients with chronic pancreatitis and 49 healthy controls undergoing the hydrogen (H2)-methane (CH4) lactulose breath test (LBT) were reviewed. The LBT positivity (+) indicating the presence of SIBO, gas types, bowel symptom questionnaire, laboratory and radiologic results were surveyed. The LBT+ was (1) an increase in the breath H2 (>=20 ppm) or CH4 (>=10 ppm) over the baseline or (2) a baseline H2 (>=20 ppm) or CH4 (>=10 ppm) within 90 min after lactulose load. RESULTS: LBT+ was significantly higher in the patients (17/36) than in controls (13/49) (47.2% vs. 26.5%, P < 0.05). During LBT, the H2 levels between 0 and 105 min were significantly higher in patients than in controls. Among LBT+ patients, 11 (64.7%), 1 (5.9%), 5 (29.4%) were in the LBT (H2)+, (CH4)+, (mixed)+ groups, respectively. The LBT+ group had significantly higher scores of flatus than those of the LBT- group. Considering the subtypes of LBT, the LBT (mixed)+ group had higher symptom scores of significance or tendency in hard stool, strain, urgency, and flatus than LBT- group The laboratory and radiologic features were not significantly different between LBT+ and LBT- groups. CONCLUSIONS: SIBO is common in patients in chronic pancreatitis. Especially, excretions of mixed H2 and CH4 appear to be related with deterioration of intestinal symptoms. PMID- 26278026 TI - Patients' adherence and clinical effectiveness of a 14-day course of primaquine when given with a 3-day chloroquine in patients with Plasmodium vivax at the Thai Myanmar border. AB - Primaquine is the only antimalarial drug available for eradicating the hypnozoite stage of Plasmodium vivax to prevent the disease from recurring. However, one limitation of its clinical use is the long treatment course of 14 days, which may result in poor patients' adherence and low treatment efficacy. The aim of the current study was to assess patients' adherence and the clinical effectiveness of the unsupervised standard 14-day primaquine regimen (daily dose of 15mg base/kg body weight daily for 14 days) when given together with 3-day chloroquine (25mg base/kg body weight over 3 days). The study was conducted in 85 patients with P. vivax malaria in a malaria endemic area along the Thai-Myanmar border. Patients' adherence to primaquine therapy was assessed based on primaquine concentrations in finger-prick dried blood spot (DBS) samples alongside patients' self-reporting on drug administration and pill counting methods. Results suggest high rate of patients' adherence to this 14-day primaquine regimen (95-98% based on primaquine concentrations in DBS on days 3, 7, and 14 of treatment, and 100% based on patients' self-reporting and pill counting methods. Clinical effectiveness was 100% during the 42-day follow-up. PMID- 26278027 TI - 1,5-Disubstituted benzimidazoles that direct cardiomyocyte differentiation from mouse embryonic stem cells. AB - Cardiomyopathy is the leading cause of death worldwide. Despite progress in medical treatments, heart transplantation is one of the only current options for those with infarcted heart muscle. Stem cell differentiation technology may afford cell-based therapeutics that may lead to the generation of new, healthy heart muscle cells from undifferentiated stem cells. Our approach is to use small molecules to stimulate stem cell differentiation. Herein, we describe a novel class of 1,5-disubstituted benzimidazoles that induce differentiation of stem cells into cardiac cells. We report on the evaluation in vitro for cardiomyocyte differentiation and describe structure-activity relationship results that led to molecules with drug-like properties. The results of this study show the promise of small molecules to direct stem cell lineage commitment, to probe signaling pathways and to develop compounds for the stimulation of stem cells to repair damaged heart tissue. PMID- 26278028 TI - Heterocyclic chalcone activators of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) with improved in vivo efficacy. AB - Nrf2 activators represent a good drug target for designing agents to treat diseases associated with oxidative stress. Building upon previous work, we designed and prepared a series of heterocyclic chalcone-based Nrf2 activators with reduced lipophilicity and, in some cases, greater in vitro potency compared to the respective carbocyclic scaffold. These changes resulted in enhanced oral bioavailability and a superior pharmacodynamic effect in vivo. PMID- 26278029 TI - Synthesis and evaluation of arylpiperazine-reverse amides as biased dopamine D3 receptor ligands. AB - The dopamine D3 receptor (D3R) preferential ligands have been universally adopted as a strategy for the treatment of drug addiction and other neuropsychiatric disorders due to fewer side effects. However, the high sequence homology between D3R and the D2 receptor (D2R) challenges the development of D3R-biased compounds. Herein, we design and synthesize a novel series of reverse amide-piperazine hybrid ligands and evaluate their biological affinities in vitro. Compound 4d was found to be the most potent D3R-selective ligand among these hybrid derivatives. Molecular modeling revealed that extracellular loop 1 (EL1) and loop 2 (EL2) of D3R together likely contribute to D3R selectivity over D2R. In particular, Gly94 in EL1 of D3R may act as a molecular determinant for D3R specificity. PMID- 26278030 TI - Journal Impact Factor: does it have an impact? PMID- 26278031 TI - Methodological issues for designing and conducting a multicenter, international clinical trial in Acute Stroke: Experience from ARTSS-2 trial. AB - BACKGROUND: We describe innovations in the study design and the efficient data coordination of a randomized multicenter trial of Argatroban in Combination with Recombinant Tissue Plasminogen Activator for Acute Stroke (ARTSS-2). METHODS: ARTSS-2 is a 3-arm, multisite/multiregional randomized controlled trials (RCTs) of two doses of Argatroban injection (low, high) in combination with recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke patients and rt-PA alone. We developed a covariate adaptive randomization program that balanced the study arms with respect to study site as well as hemorrhage after thrombolysis (HAT) score and presence of distal internal carotid artery occlusion (DICAO). We used simulation studies to validate performance of the randomization program before making any adaptations during the trial. For the first 90 patients enrolled in ARTSS-2, we evaluated performance of our randomization program using chi-square tests of homogeneity or extended Fisher's exact test. We also designed a four-step partly Bayesian safety stopping rule for low and high dose Argatroban arms. RESULTS: Homogeneity of the study arms was confirmed with respect to distribution of study site (UK sites vs. US sites, P=0.98), HAT score (0-2 vs. 3 5, P=1.0), and DICAO (N/A vs. No vs. Yes, P=0.97). Our stopping thresholds for safety of low and high dose Argatroban were not crossed. Despite challenges, data quality was assured. CONCLUSIONS: We recommend adaptive designs for randomization and Bayesian safety stopping rules for multisite Phase I/II RCTs for maintaining additional flexibility. Efficient data coordination could lead to improved data quality. PMID- 26278032 TI - Author's response: Ocular photodynamic therapy with verteporfin in pigmented and amelanotic choroidal melanoma. PMID- 26278033 TI - Letter to the editor. PMID- 26278034 TI - Retinoic acid regulates embryonic development of mammalian submandibular salivary glands. AB - Organogenesis is orchestrated by cell and tissue interactions mediated by molecular signals. Identification of relevant signals, and the tissues that generate and receive them, are important goals of developmental research. Here, we demonstrate that Retinoic Acid (RA) is a critical signaling molecule important for morphogenesis of mammalian submandibular salivary glands (SMG). By examining late stage RA deficient embryos of Rdh10 mutant mice we show that SMG development requires RA in a dose-dependent manner. Additionally, we find that active RA signaling occurs in SMG tissues, arising earlier than any other known marker of SMG development and persisting throughout gland morphogenesis. At the initial bud stage of development, we find RA production occurs in SMG mesenchyme, while RA signaling occurs in epithelium. We also demonstrate active RA signaling occurs in glands cultured ex vivo, and treatment with an inhibitor of RA signaling blocks growth and branching. Together these data identify RA signaling as a direct regulator of SMG organogenesis. PMID- 26278036 TI - VEGF signals induce trailblazer cell identity that drives neural crest migration. AB - Embryonic neural crest cells travel in discrete streams to precise locations throughout the head and body. We previously showed that cranial neural crest cells respond chemotactically to vascular endothelial growth factor (VEGF) and that cells within the migratory front have distinct behaviors and gene expression. We proposed a cell-induced gradient model in which lead neural crest cells read out directional information from a chemoattractant profile and instruct trailers to follow. In this study, we show that migrating chick neural crest cells do not display distinct lead and trailer gene expression profiles in culture. However, exposure to VEGF in vitro results in the upregulation of a small subset of genes associated with an in vivo lead cell signature. Timed addition and removal of VEGF in culture reveals the changes in neural crest cell gene expression are rapid. A computational model incorporating an integrate-and switch mechanism between cellular phenotypes predicts migration efficiency is influenced by the timescale of cell behavior switching. To test the model hypothesis that neural crest cellular phenotypes respond to changes in the VEGF chemoattractant profile, we presented ectopic sources of VEGF to the trailer neural crest cell subpopulation and show diverted cell trajectories and stream alterations consistent with model predictions. Gene profiling of trailer cells that diverted and encountered VEGF revealed upregulation of a subset of 'lead' genes. Injection of neuropilin1 (Np1)-Fc into the trailer subpopulation or electroporation of VEGF morpholino to reduce VEGF signaling failed to alter trailer neural crest cell trajectories, suggesting trailers do not require VEGF to maintain coordinated migration. These results indicate that VEGF is one of the signals that establishes lead cell identity and its chemoattractant profile is critical to neural crest cell migration. PMID- 26278035 TI - Wt1 and beta-catenin cooperatively regulate diaphragm development in the mouse. AB - The developing diaphragm consists of various differentiating cell types, many of which are not well characterized during organogenesis. One important but incompletely understood tissue, the diaphragmatic mesothelium, is distinctively present from early stages of development. Congenital Diaphragmatic Hernia (CDH) occurs in humans when diaphragm tissue is lost during development, resulting in high morbidity and mortality postnatally. We utilized a Wilms Tumor 1 (Wt1) mutant mouse model to investigate the involvement of the mesothelium in normal diaphragm signaling and development. Additionally, we developed and characterized a Wt1(CreERT2)-driven beta-catenin loss-of-function model of CDH after finding that canonical Wnt signaling and beta-catenin are reduced in Wt1 mutant mesothelium. Mice with beta-catenin loss or constitutive activation induced in the Wt1 lineage are only affected when tamoxifen injection occurs between E10.5 and E11.5, revealing a critical time-frame for Wt1/ beta-catenin activity. Conditional beta-catenin loss phenocopies the Wt1 mutant diaphragm defect, while constitutive activation of beta-catenin on the Wt1 mutant background is sufficient to close the diaphragm defect. Proliferation and apoptosis are affected, but primarily these genetic manipulations appear to lead to a change in normal diaphragm differentiation. Our data suggest a fundamental role for mesothelial signaling in proper formation of the diaphragm. PMID- 26278037 TI - Drain Management after Pancreatoduodenectomy: Reappraisal of a Prospective Randomized Trial Using Risk Stratification. AB - BACKGROUND: A recent randomized trial used the Fistula Risk Score (FRS) to develop guidelines for selective drainage based on clinically relevant fistula (CR-POPF) risk. Additionally, postoperative day (POD) 1 drain and serum amylase have been identified as accurate postoperative predictors of CR-POPF. This study sought to identify patients who may benefit from selective drainage, as well as the optimal timing for drain removal after pancreatoduodenectomy. STUDY DESIGN: One hundred six pancreatoduodenectomies from a previously reported RCT were assessed using risk-adjustment. The incidence of CR-POPF was compared between FRS risk cohorts. Drain and serum amylase values from POD 1 were evaluated using receiver operating characteristic (ROC) analysis to establish cut-offs predictive of CR-POPF occurrence. A regression analysis compared drain removal randomizations (POD 3 vs POD 5). RESULTS: Three-quarters of patients had moderate/high CR-POPF risk. This group had a CR-POPF rate of 36.3% vs 7.7% among negligible/low risk patients (p = 0.005). The areas under the ROC curve for CR POPF prediction using POD 1 drain and serum amylase values were 0.800 (p = 0.000001; 95% CI 0.70-0.90) and 0.655 (p = 0.012; 95% CI 0.55-0.77), respectively. No significant serum amylase cut-offs were identified. Moderate/high risk patients with POD 1 drain amylase <= 5,000 U/L had significantly lower rates of CR-POPF when randomized to POD 3 drain removal (4.2% vs 38.5%; p = 0.003); moreover, these patients experienced fewer complications and shorter hospital stays. CONCLUSIONS: A clinical care protocol is proposed whereby drains are recommended for moderate/high FRS risk patients, but may be omitted in patients with negligible/low risk. Drain amylase values in moderate/high risk patients should then be evaluated on POD 1 to determine the optimal timing for drain removal. Moderate/high risk patients with POD 1 drain amylase <= 5,000 U/L have lower rates of CR-POPF with POD 3 (vs POD >= 5) drain removal; early drain removal is recommended for these patients. PMID- 26278038 TI - Preoperative Tattooing for Precise and Expedient Localization of Landmark in Laparoscopic Liver Resection. PMID- 26278039 TI - Cellular and molecular remodeling of inguinal adipose tissue mitochondria by dietary methionine restriction. AB - Dietary methionine restriction (MR) produces a coordinated series of biochemical and physiological responses that improve biomarkers of metabolic health, increase energy expenditure, limit fat accretion and improve overall insulin sensitivity. Inguinal white adipose tissue (IWAT) is a primary target and site of action where the diet initiates transcriptional programs linked to enhancing both synthesis and oxidation of lipid. Using a combination of ex vivo approaches to assess dietary effects on cell morphology and function, we report that dietary MR produced a fourfold increase in multilocular, UCP1-expressing cells within this depot in conjunction with significant increases in mitochondrial content, size and cristae density. Dietary MR increased expression of multiple enzymes within the citric acid cycle, as well as respiratory complexes I, II and III. The physiological significance of these responses, evaluated in isolated mitochondria by high-resolution respirometry, was a significant increase in respiratory capacity measured using multiple substrates. The morphological, transcriptional and biochemical remodeling of IWAT mitochondria enhances the synthetic and oxidative capacity of this tissue and collectively underlies its expanded role as a significant contributor to the overall increase in metabolic flexibility and uncoupled respiration produced by the diet. PMID- 26278040 TI - PGC Reversion to Pluripotency Involves Erasure of DNA Methylation from Imprinting Control Centers followed by Locus-Specific Re-methylation. AB - Primordial germ cells (PGCs) are fate restricted to differentiate into gametes in vivo. However, when removed from their embryonic niche, PGCs undergo reversion to pluripotent embryonic germ cells (EGCs) in vitro. One of the major differences between EGCs and embryonic stem cells (ESCs) is variable methylation at imprinting control centers (ICCs), a phenomenon that is poorly understood. Here we show that reverting PGCs to EGCs involved stable ICC methylation erasure at Snrpn, Igf2r, and Kcnqot1. In contrast, the H19/Igf2 ICC undergoes erasure followed by de novo re-methylation. PGCs differentiated in vitro from ESCs completed Snrpn ICC erasure. However, the hypomethylated state is highly unstable. We also discovered that when the H19/Igf2 ICC was abnormally hypermethylated in ESCs, this is not erased in PGCs differentiated from ESCs. Therefore, launching PGC differentiation from ESC lines with appropriately methylated ICCs is critical to the generation of germline cells that recapitulate endogenous ICC erasure. PMID- 26278041 TI - Reprogramming Roadblocks Are System Dependent. AB - Since the first generation of induced pluripotent stem cells (iPSCs), several reprogramming systems have been used to study its molecular mechanisms. However, the system of choice largely affects the reprogramming efficiency, influencing our view on the mechanisms. Here, we demonstrate that reprogramming triggered by less efficient polycistronic reprogramming cassettes not only highlights mesenchymal-to-epithelial transition (MET) as a roadblock but also faces more severe difficulties to attain a pluripotent state even post-MET. In contrast, more efficient cassettes can reprogram both wild-type and Nanog(-/-) fibroblasts with comparable efficiencies, routes, and kinetics, unlike the less efficient reprogramming systems. Moreover, we attribute a previously reported variation in the N terminus of KLF4 as a dominant factor underlying these critical differences. Our data establish that some reprogramming roadblocks are system dependent, highlighting the need to pursue mechanistic studies with close attention to the systems to better understand reprogramming. PMID- 26278042 TI - Cell-Cycle Control of Bivalent Epigenetic Domains Regulates the Exit from Pluripotency. AB - Here we show that bivalent domains and chromosome architecture for bivalent genes are dynamically regulated during the cell cycle in human pluripotent cells. Central to this is the transient increase in H3K4-trimethylation at developmental genes during G1, thereby creating a "window of opportunity" for cell-fate specification. This mechanism is controlled by CDK2-dependent phosphorylation of the MLL2 (KMT2B) histone methyl-transferase, which facilitates its recruitment to developmental genes in G1. MLL2 binding is required for changes in chromosome architecture around developmental genes and establishes promoter-enhancer looping interactions in a cell-cycle-dependent manner. These cell-cycle-regulated loops are shown to be essential for activation of bivalent genes and pluripotency exit. These findings demonstrate that bivalent domains are established to control the cell-cycle-dependent activation of developmental genes so that differentiation initiates from the G1 phase. PMID- 26278043 TI - Effect of proton and gamma irradiation on human lung carcinoma cells: Gene expression, cell cycle, cell death, epithelial-mesenchymal transition and cancer stem cell trait as biological end points. AB - Proton beam therapy is a cutting edge modality over conventional gamma radiotherapy because of its physical dose deposition advantage. However, not much is known about its biological effects vis-a-vis gamma irradiation. Here we investigated the effect of proton- and gamma- irradiation on cell cycle, death, epithelial-mesenchymal transition (EMT) and "stemness" in human non-small cell lung carcinoma cells (A549). Proton beam (3MeV) was two times more cytotoxic than gamma radiation and induced higher and longer cell cycle arrest. At equivalent doses, numbers of genes responsive to proton irradiation were ten times higher than those responsive to gamma irradiation. At equitoxic doses, the proton irradiated cells had reduced cell adhesion and migration ability as compared to the gamma-irradiated cells. It was also more effective in reducing population of Cancer Stem Cell (CSC) like cells as revealed by aldehyde dehydrogenase activity and surface phenotyping by CD44(+), a CSC marker. These results can have significant implications for proton therapy in the context of suppression of molecular and cellular processes that are fundamental to tumor expansion. PMID- 26278044 TI - A gold nanoparticle-based fluorescence sensor for high sensitive and selective detection of thiols in living cells. AB - A novel gold nanoparticle (AuNP)-based sensor for detecting thiols in aqueous solution has been developed. Due to the weak N...Au interactions, meso-(4 pyridinyl)-substituted BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) dyes were coordinated to AuNP surfaces, which effectively quenched the fluorescence of organic/inorganic hybrid systems. The fluorescent quenching mechanism was mainly ascribed to the highly efficient fluorescent resonance energy transfer (FRET) and the inner filter effect. In the presence of thiols, meso-(4-pyridinyl) substituted BODIPY chromophore were displaced and released from the AuNP surfaces and thus restored the fluorescence of BODIPY chromophore. The modulation of the fluorescence quenching efficiency of BODIPY-AuNPs in the presence of thiols can achieve a large turn-on fluorescence enhancement (40-fold) in aqueous solution. The new AuNP-based fluorescence sensor displayed desired properties such as high specificity, relatively low detection limit (30 nM for Cys), appreciable water solubility and rapid response time (within 2 min for Cys/Hcy). Moreover, the sensor has been successfully applied for monitoring and imaging of intracellular thiols within living HeLa cells. PMID- 26278045 TI - Stimulus-response mesoporous silica nanoparticle-based chemiluminescence biosensor for cocaine determination. AB - Mesoporous silica nanoparticles (MSN) based controlled release system had been coupled with diverse detection technologies to establish biosensors for different targets. Chemiluminescence (CL) system of luminol/H2O2 owns the characters of simplicity, low cost and high sensitivity, but the targets of which are mostly focused on some oxidants or which can participate in a chemical reaction that yields a product with a role in the CL reaction. In this study, chemiluminescent detection technique had been coupled with mesoporous silica-based controlled released system for the first time to develop a sensitive biosensor for the target which does not cause effect to the CL system itself. Cocaine had been chosen a model target, the MSN support was firstly loaded with glucose, then the positively charged MSN interacted with negatively charged oligonucleotides (the aptamer cocaine) to close the mesopores of MSN. At the present of target, cocaine binds with its aptamer with high affinity; the flexible linear aptamer structured will become stems structured through currently well-defined non-Waston-Crick interactions and causes the releasing of entrapped glucose into the solution. With the assistant of glucose oxidase (GOx), the released glucose can react with the dissolved oxgen to produce gluconic acid and H2O2, the latter can enhance the CL of luminol in the NaOH solution. The enhanced CL intensity has a relationship with the cocaine concentration in the range of 5.0-60MUM with the detection limit of 1.43MUM. The proposed method had been successfully applied to detect cocaine in serum samples with high selectivity. The same strategy can be applied to develop biosensors for different targets. PMID- 26278047 TI - Structural Organization of Insulin Fibrils Based on Polarized Raman Spectroscopy: Evaluation of Existing Models. AB - Many different proteins undergo misfolding and self-assemble into amyloid fibrils, resulting in a range of neurodegenerative diseases. The limitations of conventional methods of structural biology for fibril characterization have led to the use of polarized Raman spectroscopy for obtaining quantitative structural information regarding the organization of amyloid fibrils. Herein, we report the orientation of selected chemical groups and secondary structure elements in aligned insulin fibrils, including beta-sheets, which possess a high level of orientation in the cross-beta core, and alpha-helices in the disordered portions of the fibrils. Strong orientation of disulfide bonds in amyloid fibrils was also revealed, indicating their association with the fibril core. The determined orientation of chemical groups provides strong constraints for modeling the overall structure of amyloid fibrils, including the core and disordered parts. The developed methodology allows for the validation of structural models proposed in the literature for amyloid fibrils. Specifically, the polarized Raman data obtained herein strongly agreed with two insulin fibril models (Jimenez et al., Proc. Natl. Acad. Sci. U. S. A. 2002, 99, 9196-9201 and Ivanova et al., Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 18990-18995) yet revealed significant qualitative and quantitative differences. This work demonstrates the great potential of polarized Raman spectroscopy for structural characterization of anisotropic biological species. PMID- 26278046 TI - Escalation to High-Dose Defibrotide in Patients with Hepatic Veno-Occlusive Disease. AB - Hepatic veno-occlusive disease (VOD) is a serious complication of high-dose chemotherapy regimens, such as those used in hematopoietic cell transplantation recipients. Defibrotide is considered a safe and effective treatment when dosed at 25 mg/kg/day. However, patients who develop VOD still have increased mortality despite the use of defibrotide. Data are limited on the use of doses above 60 mg/kg/day for persistent VOD. In this prospective clinical trial 34 patients received escalating doses of defibrotide. For patients with persistent VOD despite doses of 60 mg/kg/day, doses were increased to a maximum of 110 mg/kg/day. Increased toxicity was not observed until doses rose beyond 100 mg/kg/day. Patients receiving doses between 10 and 100 mg/kg/day experienced an average of 3 bleeding episodes per 100 days of treatment, whereas those receiving doses >100 mg/kg/day experienced 13.2 bleeding episodes per 100 days (P = .008). Moreover, dose reductions due to toxicity were needed at doses of 110 mg/kg/day more often than at lower doses. Defibrotide may be safely escalated to doses well above the current standard without an increase in bleeding risk. However, the efficacy of this dose-escalation strategy remains unclear, because outcomes were similar to published cohorts of patients receiving standard doses of defibrotide for VOD. PMID- 26278048 TI - Passive sinking into the snow as possible survival strategy during the off-host stage in an insect ectoparasite. AB - Abiotic and biotic factors determine success or failure of individual organisms, populations and species. The early life stages are often the most vulnerable to heavy mortality due to environmental conditions. The deer ked (Lipoptena cervi Linnaeus, 1758) is an invasive insect ectoparasite of cervids that spends an important period of the life cycle outside host as immobile pupa. During winter, dark-coloured pupae drop off the host onto the snow, where they are exposed to environmental temperature variation and predation as long as the new snowfall provides shelter against these mortality factors. The other possible option is to passively sink into the snow, which is aided by morphology of pupae. Here, we experimentally studied passive snow sinking capacity of pupae of L. cervi. We show that pupae have a notable passive snow sinking capacity, which is the most likely explained by pupal morphology enabling solar energy absorption and pupal weight. The present results can be used when planning future studies and when evaluating possible predation risk and overall survival of this invasive ectoparasite species in changing environmental conditions. PMID- 26278049 TI - ER Stress and Angiogenesis. AB - Proper tissue vascularization is vital for cellular function as it delivers oxygen, nutrients, hormones, and immune cells and helps to clear cellular debris and metabolic waste products. Tissue angiogenesis occurs to satisfy energy requirements and cellular sensors of metabolic imbalance coordinate vessel growth. In this regard, the classical pathways of the unfolded protein response activated under conditions of ER stress have recently been described to generate angiomodulatory or angiostatic signals. This review elaborates on the link between angiogenesis and ER stress and discusses the implications for diseases characterized by altered vascular homeostasis, such as cancer, retinopathies, and atherosclerosis. PMID- 26278050 TI - Palatability Can Drive Feeding Independent of AgRP Neurons. AB - Feeding behavior is exquisitely regulated by homeostatic and hedonic neural substrates that integrate energy demand as well as the reinforcing and rewarding aspects of food. Understanding the net contribution of homeostatic and reward driven feeding has become critical because of the ubiquitous source of energy dense foods and the consequent obesity epidemic. Hypothalamic agouti-related peptide-secreting neurons (AgRP neurons) provide the primary orexigenic drive of homeostatic feeding. Using models of neuronal inhibition or ablation, we demonstrate that the feeding response to a fast ghrelin or serotonin receptor agonist relies on AgRP neurons. However, when palatable food is provided, AgRP neurons are dispensable for an appropriate feeding response. In addition, AgRP ablated mice present exacerbated stress-induced anorexia and palatable food intake--a hallmark of comfort feeding. These results suggest that, when AgRP neuron activity is impaired, neural circuits sensitive to emotion and stress are engaged and modulated by food palatability and dopamine signaling. PMID- 26278051 TI - Detection and Quantitation of Circulating Human Irisin by Tandem Mass Spectrometry. AB - Exercise provides many health benefits, including improved metabolism, cardiovascular health, and cognition. We have shown previously that FNDC5, a type I transmembrane protein, and its circulating form, irisin, convey some of these benefits in mice. However, recent reports questioned the existence of circulating human irisin both because human FNDC5 has a non-canonical ATA translation start and because of claims that many human irisin antibodies used in commercial ELISA kits lack required specificity. In this paper we have identified and quantitated human irisin in plasma using mass spectrometry with control peptides enriched with heavy stable isotopes as internal standards. This precise state-of-the-art method shows that human irisin is mainly translated from its non-canonical start codon and circulates at ~ 3.6 ng/ml in sedentary individuals; this level is increased to ~ 4.3 ng/ml in individuals undergoing aerobic interval training. These data unequivocally demonstrate that human irisin exists, circulates, and is regulated by exercise. PMID- 26278053 TI - One Strike against Low-Carbohydrate Diets. AB - There is intense controversy over whether low-carbohydrate or low-fat diets are more efficacious for weight management. Using precise methodology, Hall et al. (2015) demonstrated that a low-carbohydrate diet promoted greater fat oxidation than an isocaloric low-fat diet but, in contrast to popular speculation, did not cause greater body fat loss. PMID- 26278052 TI - Calorie for Calorie, Dietary Fat Restriction Results in More Body Fat Loss than Carbohydrate Restriction in People with Obesity. AB - Dietary carbohydrate restriction has been purported to cause endocrine adaptations that promote body fat loss more than dietary fat restriction. We selectively restricted dietary carbohydrate versus fat for 6 days following a 5 day baseline diet in 19 adults with obesity confined to a metabolic ward where they exercised daily. Subjects received both isocaloric diets in random order during each of two inpatient stays. Body fat loss was calculated as the difference between daily fat intake and net fat oxidation measured while residing in a metabolic chamber. Whereas carbohydrate restriction led to sustained increases in fat oxidation and loss of 53 +/- 6 g/day of body fat, fat oxidation was unchanged by fat restriction, leading to 89 +/- 6 g/day of fat loss, and was significantly greater than carbohydrate restriction (p = 0.002). Mathematical model simulations agreed with these data, but predicted that the body acts to minimize body fat differences with prolonged isocaloric diets varying in carbohydrate and fat. PMID- 26278054 TI - [Call for applications for the post of Editor of the Revista Medica de Chile]. PMID- 26278055 TI - Roles of NGAL and MMP-9 in the tumor microenvironment and sensitivity to targeted therapy. AB - Various, diverse molecules contribute to the tumor microenvironment and influence invasion and metastasis. In this review, the roles of neutrophil gelatinase associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9) in the tumor microenvironment and sensitivity to therapy will be discussed. The lipocalin family of proteins has many important functions. For example when NGAL forms a complex with MMP-9 it increases its stability which is important in cancer metastasis. Small hydrophobic molecules are bound by NGAL which can alter their entry into and efflux from cells. Iron transport and storage are also influenced by NGAL activity. Regulation of iron levels is important for survival in the tumor microenvironment as well as metastasis. Innate immunity is also regulated by NGAL as it can have bacteriostatic properties. NGAL and MMP-9 expression may also affect the sensitivity of cancer cells to chemotherapy as well as targeted therapy. Thus NGAL and MMP-9 play important roles in key processes involved in metastasis as well as response to therapy. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza. PMID- 26278056 TI - Color-dye injection of monochorionic placentas and correlation with pregnancy complications. AB - INTRODUCTION: Vascular anastomoses in monochorionic (MC) twin placenta can be easily identified with color-dye injection. The aim of this study is to analyze the relationship between different type of anastomoses and twin pregnancy complications. METHODS: From January 2011 to October 2014, MC placentas were analyzed with color-dye injection and five group of pregnancies were identified: those that were not complicated (NC), those complicated with selective intrauterine growth restriction (sIUGR), twin-twin transfusion syndrome (TTTS), or twin anemia-polycitemia sequence (TAPS) and those with amniotic fluid discordance (AFD) between twins. Cases of TTTS treated with endoscopic laser coagulation of placenta anastomoses or cases with in utero death of one twin were excluded. RESULTS: A total of 118 MC placentas were observed, 58 (49%) NC, 35 (30%) sIUGR, 10 (8%) TTTS, 13 (11%) AFD and 2 (2%) TAPS. The median number of anastomoses was 7 (range 1-15), 8 (2-18), 4 (2-11), 7 (2-13) and 1 (1-1), respectively. At least one artero-venous anastomoses was found in the placenta observed, while the prevalence of artero-arterial anastomoses was 95% for NC, 91% for sIUGR, 60% for TTTS, and 77% for AFD; no TAPS placenta had this type of anastomoses. The diameter of arteroarterial anastomoses was greater in the AFD group (3.3 mm), compared to the NC, sIUGR and TTTS groups (2.3, 2.5 and 1.4 respectively, p 0.04). DISCUSSION: In this large serie of MC placenta analyzed with color-dye injection, a specific distribution of anastomoses emerged for twins with amniotic fluid discordance, which points to a need for intensive surveillance. PMID- 26278058 TI - Maternal fish consumption, fatty acid levels and angiogenic factors: The Generation R Study. AB - INTRODUCTION: Angiogenic factors, such as placental growth factor (PlGF) and soluble Flt-1 (sFlt-1), are key regulators of placental vascular development. Evidence from in vitro studies indicates that fatty acids can affect angiogenesis. We investigated the associations of maternal fish consumption and fatty acids levels with angiogenic factors during pregnancy, and in cord blood in a large population-based prospective cohort. METHODS: First trimester fish consumption was assessed among 3134 pregnant women using a food-frequency questionnaire. Plasma fatty acid levels were measured in second trimester. Plasma PlGF and sFlt-1 were measured in first and second trimester and in cord blood. Associations of fish consumption or fatty acid levels with angiogenic factors were assessed by multivariable linear regression analyses. RESULTS: There were no consistent associations of total fish or lean fish consumption with levels of PlGF, sFlt-1, or sFlt-1/PlGF ratio. Neither fatty fish nor shellfish were associated with angiogenic factors. Plasma omega-3 polyunsaturated fatty acids, which are the main type of fatty acids in fish, were inconsistently associated with angiogenic factors in second trimester and cord blood. Yet, higher levels of arachidonic acid, an omega-6 polyunsaturated fatty acid, were associated with lower levels of PlGF and sFlt-1. DISCUSSION: We found no consistent associations of fish consumption or fatty acids levels with angiogenic factors in a population with low fish consumption. Studies including populations with higher fish consumption are required to fully grasp the potential effects of maternal fish consumption on placental angiogenesis. PMID- 26278057 TI - Hypoplastic left heart syndrome is associated with structural and vascular placental abnormalities and leptin dysregulation. AB - INTRODUCTION: Hypoplastic left heart syndrome (HLHS) is a severe cardiovascular malformation (CVM) associated with fetal growth abnormalities. Genetic and environmental factors have been identified that contribute to pathogenesis, but the role of the placenta is unknown. The purpose of this study was to systematically examine the placenta in HLHS with and without growth abnormalities. METHODS: HLHS term singleton births were identified from a larger cohort when placenta tissue was available. Clinical data were collected from maternal and neonatal medical records, including anthropometrics and placental pathology reports. Placental tissues from cases and controls were analyzed to assess parenchymal morphology, vascular architecture and leptin signaling. RESULTS: HLHS cases (n = 16) and gestational age-matched controls (n = 18) were analyzed. Among cases, the average birth weight was 2993 g, including 31% that were small for gestational age. When compared with controls, gross pathology of HLHS cases demonstrated significantly reduced placental weight and increased fibrin deposition, while micropathology showed increased syncytial nuclear aggregates, decreased terminal villi, reduced vasculature and increased leptin expression in syncytiotrophoblast and endothelial cells. DISCUSSION: Placentas from pregnancies complicated by fetal HLHS are characterized by abnormal parenchymal morphology, suggesting immature structure may be due to vascular abnormalities. Increased leptin expression may indicate an attempt to compensate for these vascular abnormalities. Further investigation into the regulation of angiogenesis in the fetus and placenta may elucidate the causes of HLHS and associated growth abnormalities in some cases. PMID- 26278059 TI - Feto-maternal immune regulation by TIM-3/galectin-9 pathway and PD-1 molecule in mice at day 14.5 of pregnancy. AB - INTRODUCTION: Immunoregulation implies the activation of negative pathways leading to the modulation of specific immune responses. Co-inhibitory receptors (such as PD-1 and TIM-3) represent possible tools for this purpose. PD-1 and TIM 3 have been demonstrated to be present on immune cells suggesting general involvement in immunosuppression such as fetomaternal tolerance. The aim of our study was to investigate the expression pattern of PD-1, TIM-3, and its ligand Gal-9 on different immune cell subsets in the peripheral blood and at the fetomaternal interface in pregnant mice. METHODS: TIM-3 and PD-1 expression by peripheral and decidual immune cells from pregnant BALB-c mice in 2 weeks of gestational age were measures by flow cytometry. Placental galectin-9 expression was determined by immunohistochemically and RT-PCR. RESULTS: Gal-9 was found to be present in the spongiotrophoblast layer of the haemochorial placenta. Decidual NK, NKT and gamma/delta T cells showed increased PD-1 expression and reduced cytotoxic potential when compared to the periphery. TIM-3 expression by NK cells and gamma/delta T cells is similar both in the periphery and in the decidua, notably, their relative TIM-3 expression is increased locally which is associated with reduced lytic activity. Decidual NKT cells exhibit a reduced TIM-3 expression with increased relative receptor expression and a slightly increased cytotoxicity when compared to the periphery. DISCUSSION: Our data reveals a particularly complex, tissue and cell type specific immunoregulatory mechanism by the investigated co-inhibitory receptors at the fetomaternal interface. PMID- 26278060 TI - Activation of A-H bonds (A = B, C, N, O, Si) by using monovalent phosphorus complexes [RP->M]. AB - The available data on the activation of A-H sigma bonds by electrophilic terminal phosphinidene complexes are reviewed. Theoretical computations allow us to rationalize the experimental results. It appears that a successful insertion needs an initial interaction between the phosphinidene and the A-H bond, such as a donor-acceptor complex with a lone pair, a Coulombic interaction due to a negative charge on A or H, or a proximity effect. PMID- 26278061 TI - Surface effect on the electromelting behavior of nanoconfined water. AB - Electric field induced phase transitions of confined water have an important role in cryopreservation and electrocrystallization. In this study, the structural and dynamical properties of nano-confined water in nano-slit pores under the influence of an electric field varying from 0 to 10 V nm(-1) are investigated under ambient conditions using molecular dynamics simulations. In order to replicate the nature of different materials, a systematic approach is adopted, including pore-size and lattice constant variations in different lattice arrangements viz., triangular, square and hexagonal, with hydrophilic and hydrophobic surface-fluid interactions. The structural behavior of water is investigated using radial distribution functions, bond order parameters and hydrogen bond calculations; the dynamical properties are analyzed using lateral and rotational diffusivity calculations. The lateral diffusivity with increasing electric field E increases by order(s) of magnitude during electromelting. The pore-size, lattice constant, lattice arrangement and hydrophobic/hydrophilic nature of the pore surface strongly influence the electromelting behavior for E<=~7 V nm(-1). Higher values of lattice constants and/or hydrophobic pores enhance the electromelting behavior of nanoconfined water. PMID- 26278062 TI - Heat-induced formation of one-dimensional coordination polymers on Au(111): an STM study. AB - The formation of one-dimensional coordination polymers of cyano-substituted porphyrin derivatives on Au(111) induced by thermal annealing is demonstrated by means of scanning tunnelling microscopy. The polymer is stabilised by an unusual threefold coordination motif mediated between an Au atom and the cyano groups of the porphyrin derivatives. PMID- 26278063 TI - Reduction in short-acting insulin requirement accompanies improved glycemic control with basal insulin peglispro compared with insulin glargine in patients with type 1 diabetes. PMID- 26278064 TI - Longitudinal clines in the frequency distribution of 'super-clones' in an aphid crop pest. AB - Parthenogenesis is the main mode of reproduction of aphids. Their populations are therefore composed of clones whose frequency distribution varies in space and time. Previous population genetic studies on aphids have highlighted the existence of highly abundant clones ('super-clones'), distributed over large geographic areas and persisting over time. Whether the abundance of 'super clones' results from their ecological success or from stochastic forces, such as drift and migration, is an open question. Here, we looked for the existence of clines in clonal frequency along a climatic gradient in the cereal aphid Rhopalosiphum padi (Linnaeus, 1758) and examined the possible influence of geographical distance and environmental variables in the buildup and maintenance of such clonal clines. We investigated the spatial distribution of the commonest genotypes of R. padi by sampling populations along an east-west transect in maize fields in the northern half of France in both spring and late summer. Individual aphids were genotyped at several polymorphic loci, allowing the assessment of frequency distributions of multilocus genotypes (MLGs) across the cropping season. We found several MLGs showing longitudinal clines in their frequency distribution in both spring and summer. In particular, two dominant asexual genotypes of R. padi showed inverted geographical clines, which could suggest divergent adaptations to environmental conditions. We concluded that while the distribution of some 'super-clones' of R. padi seems most likely driven by the action of migration and genetic drift, selection could be also involved in the establishment of longitudinal clines of others. PMID- 26278065 TI - Glucosamine condensation catalyzed by 1-ethyl-3-methylimidazolium acetate: mechanistic insight from NMR spectroscopy. AB - The basic ionic liquid 1-ethyl-3-methylimidazolium acetate ([C2C1Im][OAc]) could efficiently catalyze the conversion of 2-amino-2-deoxy-d-glucose (GlcNH2) into deoxyfructosazine (DOF) and fructosazine (FZ). Mechanistic investigation by NMR studies disclosed that [C2C1Im][OAc], exhibiting strong hydrogen bonding basicity, could coordinate with the hydroxyl and amino groups of GlcNH2via the promotion of hydrogen bonding in bifunctional activation of substrates and further catalyzing product formation, based on which a plausible reaction pathway involved in this homogeneous base-catalyzed reaction was proposed. Hydrogen bonding as an activation force, therefore, is responsible for the remarkable selectivity and rate enhancement observed. PMID- 26278066 TI - A call for consensus on upper airway terminology. PMID- 26278067 TI - Letter to the Editor: Validation of IgG cut-off values and their association with survival in neonatal foals. PMID- 26278068 TI - Validation of IgG cut-off values and their association with survival in neonatal foals: a response. PMID- 26278069 TI - Mild hemophilia A patient with novel Pro1809Leu mutation develops an anti-C2 antibody inhibiting allogeneic but not autologous factor VIII activity. AB - BACKGROUND: In mild hemophilia A (MHA) patients, the risk of inhibitor development is generally low, but some factor VIII (FVIII) gene missense mutations are associated with a higher inhibitor incidence. OBJECTIVE: To investigate the mechanism(s) of inhibitor development in MHA. METHODS AND RESULTS: A patient, HA78, with MHA with a novel P1809L missense mutation in the A3 domain, exhibited significant residual FVIII activity ( FVIII: C ~10 IU dL(-1) ), despite the development of an inhibitor (5.6 BU mL(-1) ). Purified HA78-IgG significantly depressed FVIII: C from normal plasma but not from patient's plasma without inhibitor, indicating that this IgG inhibited allogeneic but not autologous FVIII. The HA78-IgG blocked thrombin and FXa-catalyzed FVIII cleavage but had little effect on FVIII binding to von Willebrand factor and phospholipid. The IgG recognized a C2 epitope close or overlapping the previously described anti-C2 ESH8 epitope. Similarly, a recombinant FVIII-P1809L mutant was little inactivated by HA78-IgG. This mutant demonstrated ~3-fold lower binding affinities to von Willebrand factor and phospholipid compared with wild-type, while reactions with thrombin or FXa were not impaired. Reaction of FVIII-P1809L with the alternative anti-C2 ESH4 showed only an ~20% inhibition compared with wild-type FVIII but was similar to wild-type after incubation with ESH8. A surface plasmon resonance-based assay demonstrated that anti-C2 ESH4 bound to FVIII-P1809L with ~10(2) -fold lower affinity compared with ESH8. CONCLUSION: These results indicated that the P1809L mutation in A3 induced the conformational change in the FVIII molecule that hampered antigenic determinant(s) located in the C2 domain and might result in the inhibitor development. PMID- 26278070 TI - Responsive Stabilization of Nanoparticles for Extreme Salinity and High Temperature Reservoir Applications. AB - Colloidal stabilization of nanoparticles under extreme salinity and high temperature conditions is a key challenge in the development of next generation technologies for subsurface reservoir characterization and oil recovery. Polyelectrolytes have been investigated as nanoparticle stabilizers, but typically fail at high ionic strengths and elevated temperatures due to excessive charge screening and dehydration. We report an approach to nanoparticle stabilization that overcomes these limitations, and exploits the antipolyelectrolyte phenomenon, in which screening of intrachain electrostatic interactions causes a polyzwitterion chain to undergo a structural transition from a collapsed globule to a more open coil-like regime with increases in ionic strength and temperature. Small-angle neutron scattering on a model zwitterionic polymer in solution indicated an increase in both radius of gyration and excluded volume parameter of the polymer with increases in ionic strength and temperature. The model zwitterion was subsequently incorporated within a polymeric stabilizer for nanoparticles under harsh reservoir conditions, and used to functionalize hydrophilic (silica) as well as hydrophobic (polystyrene) nanoparticles. Long term colloidal stability was achieved at salt concentrations up to 120,000 mg/dm3 at 90 degrees C, approximately twice the stability limit previously reported in the literature. The approach can be broadly generalized to a large class of synthetic polyzwitterions, and can be adapted to a wide variety of other colloidal systems in which demands placed by extreme salinity and temperature conditions must be met. PMID- 26278071 TI - Erratum. AB - In the article by Zhou Y, Zhang J, Zhu M, Lu R, Wang Y and Ni Z, entitled "Plasma pentraxin 3 is closely associated with peripheral arterial disease in hemodialysis patients and predicts clinical outcome: a 6-year follow-up" [Blood Purif 2015;39:266-273, DOI: 10.1159/000381254], the institutional affiliations should be corrected as follows: Yijun Zhou, Jiwei Zhang, Mingli Zhu, Renhua Lu, Yongmei Wang, Zhaohui Ni. Department of Nephrology, and Vascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China PMID- 26278073 TI - IL-29 Enhances LPS/TLR4-Mediated Inflammation in Rheumatoid Arthritis. AB - BACKGROUND/AIMS: Interleukin-29 (IL-29), a critical member of type III interferons (IFNs) family, has been implicated in protecting against viral infection and modulating autoimmune inflammation. Toll-like receptor 4 (TLR4) plays a crucial role in synovial inflammation and may contribute to the pathogenesis of rheumatology arthritis (RA). However, little is known about the modifying effect of IL-29 on TLR4-mediated inflammation in RA. We aim to investigate the potential association between IL-29 and TLR4 in RA. METHODS: Peripheral blood mononuclear cells (PBMCs) and serum from 77 patients with RA and 70 controls were collected to determine levels of IL-29 and TLR4 mRNA by real time polymerase chain reaction (PCR). Levels of IL-29 and TLR4 in synovial tissues and fluid from 25 RA patients and 24 controls were detected by enzyme linked immunosorbent assay (ELISA) or western blot assay, respectively. RAW264.7 cells were stimulated by lipopolysaccharide (LPS) and/or IL-29. The production of inflammatory cytokines including IL-6, IL-8 as well as TNF-alpha and the activation of nuclear factor-kappaB (NF-kappaB) signaling were determined. RESULTS: In comparison with controls, increased IL-29 was observed in PBMCs, synovial tissue, serum and synovial fluid of patients with RA. Besides, TLR4 was significantly elevated in PBMCs and synovium of RA patients. Moreover, IL-29 was positively associated with TLR4 in RA, suggested by Pearson's correlation analysis. When RAW264.7 cells were stimulated by LPS with or without IL-29 in vitro, IL-29 could enhance LPS-mediated TLR4 expression and the production of IL 6, IL-8 and TNF-alpha in RAW264.7 cells via the activation of NF-kappaB signaling. CONCLUSION: The present study suggests, for the first time, that IL-29 can aggravate LPS/TLR4-mediated inflammation in RA depending on NF-kappaB signaling activation. PMID- 26278074 TI - The Effect of a Complex Multi-modality Ayurvedic Treatment in a Case of Unknown Female Infertility. AB - BACKGROUND: Treatment of female infertility has been growing globally in recent years. In spite of improvements in medical strategies and the improved outcomes for infertile couples, treatment attempts remain largely unsuccessful. A growing number of patients pursue complementary and alternative medicine treatment options like Ayurveda that offers a variety of inpatient and outpatient treatments for infertility. CASE REPORT: A case of a 38 year-old woman with infertility of unknown origin is presented. She received 18 conventional fertility treatments in 5 different fertility centers and 3 different countries. After several complications, the patient quitted conventional treatment and admitted to an Ayurvedic outpatient clinic where she received a complex Ayurvedic treatment, which included botanicals, dietary and lifestyle advice, manual therapy, yoga, and spiritual elements. The patient then became pregnant and gave birth to a healthy boy in 2012. CONCLUSIONS: Ayurveda may be a useful complementary option in the case of futile conventional treatment attempts in female infertility. Nevertheless, the evidence base for Ayurvedic interventions remains weak and requires well-designed clinical trials. This case raises some questions, such as whether the exposure to a large number of assisted reproduction procedures can lead to more health problems than health benefits. The Ayurvedic approach to fertility strives first to improve the health of the patient leading to a higher likelihood of pregnancy. As this is a case report, we are not able to exclude temporal factors stimulating the pregnancy. However, the chronology suggests that this approach might have been an important factor in the eventual pregnancy. PMID- 26278072 TI - Global burden of disease due to smokeless tobacco consumption in adults: analysis of data from 113 countries. AB - BACKGROUND: Smokeless tobacco is consumed in most countries in the world. In view of its widespread use and increasing awareness of the associated risks, there is a need for a detailed assessment of its impact on health. We present the first global estimates of the burden of disease due to consumption of smokeless tobacco by adults. METHODS: The burden attributable to smokeless tobacco use in adults was estimated as a proportion of the disability-adjusted life-years (DALYs) lost and deaths reported in the 2010 Global Burden of Disease study. We used the comparative risk assessment method, which evaluates changes in population health that result from modifying a population's exposure to a risk factor. Population exposure was extrapolated from country-specific prevalence of smokeless tobacco consumption, and changes in population health were estimated using disease specific risk estimates (relative risks/odds ratios) associated with it. Country specific prevalence estimates were obtained through systematically searching for all relevant studies. Disease-specific risks were estimated by conducting systematic reviews and meta-analyses based on epidemiological studies. RESULTS: We found adult smokeless tobacco consumption figures for 115 countries and estimated burden of disease figures for 113 of these countries. Our estimates indicate that in 2010, smokeless tobacco use led to 1.7 million DALYs lost and 62,283 deaths due to cancers of mouth, pharynx and oesophagus and, based on data from the benchmark 52 country INTERHEART study, 4.7 million DALYs lost and 204,309 deaths from ischaemic heart disease. Over 85 % of this burden was in South-East Asia. CONCLUSIONS: Smokeless tobacco results in considerable, potentially preventable, global morbidity and mortality from cancer; estimates in relation to ischaemic heart disease need to be interpreted with more caution, but nonetheless suggest that the likely burden of disease is also substantial. The World Health Organization needs to consider incorporating regulation of smokeless tobacco into its Framework Convention for Tobacco Control. PMID- 26278075 TI - Alcohol and remembering a hypothetical sexual assault: Can people who were under the influence of alcohol during the event provide accurate testimony? AB - We examined the influence of alcohol on remembering an interactive hypothetical sexual assault scenario in the laboratory using a balanced placebo design. Female participants completed a memory test 24 hours and 4 months later. Participants reported less information (i.e., responded "don't know" more often to questions) if they were under the influence of alcohol during scenario encoding. The accuracy of the information intoxicated participants reported did not differ compared to sober participants, however, suggesting intoxicated participants were effectively monitoring the accuracy of their memory at test. Additionally, peripheral details were remembered less accurately than central details, regardless of the intoxication level; and memory accuracy for peripheral details decreased by a larger amount compared to central details across the retention interval. Finally, participants were more accurate if they were told they were drinking alcohol rather than a placebo. We discuss theoretical implications for alcohol myopia and memory regulation, together with applied implications for interviewing intoxicated witnesses. PMID- 26278076 TI - The Role of Broken Symmetry in Solvation of a Spherical Cavity in Classical and Quantum Water Models. AB - Insertion of a hard sphere cavity in liquid water breaks translational symmetry and generates an electrostatic potential difference between the region near the cavity and the bulk. Here, we clarify the physical interpretation of this potential and its calculation. We also show that the electrostatic potential in the center of small, medium, and large cavities depends very sensitively on the form of the assumed molecular interactions for different classical simple point charge models and quantum mechanical DFT-based interaction potentials, as reflected in their description of donor and acceptor hydrogen bonds near the cavity. These differences can significantly affect the magnitude of the scalar electrostatic potential. We argue that the result of these studies will have direct consequences toward our understanding of the thermodynamics of ion solvation through the cavity charging process. PMID- 26278077 TI - Kinetically Controlled Self-Assembly of Latex-Microgel Core-Satellite Particles. AB - Latex-microgel core-satellite particles were prepared by electrostatic assembly of negatively charged polystyrene latex and positively charged microgels of a poly(N-isopropylmethacrylamide) (pNIPMAM) and poly[2-methacryloyloxy)ethyl] trimethylammonium chloride (pMETAC) copolymer. The number of satellites per core, determined by scanning electron microscopy, varied from 3 to 10 depending on the sizes of the microgel and latex microparticles. The numbers of satellites per core for different size ratios were compared with the predictions for thermodynamically controlled (maximum packing) and kinetically controlled (random sequential adsorption) assembly, and it was shown that the assembly of latex and microgel proceeds through a random sequential adsorption mechanism. The charges of the microgels and latex particles were retained within the assemblies; therefore, the core-satellite particles have well-defined regions of positive and negative charge. These regions were used to direct the adsorption of gold and latex nanoparticles of opposite charge in order to create multicomponent colloids. PMID- 26278078 TI - Proton-Triggered Hypsochromic Luminescence in 1,1'-(2,5-Distyryl-1,4-phenylene) Dipiperidine. AB - A proton-triggered hypsochromic luminescent chromophore 1,1'-(2,5-distyryl-1,4 phenylene) dipiperidine (DPD) was designed and synthesized. Upon treatment by hydrochloric acid (HCl), the emission of DPD showed a large hypsochromic shift in both THF solution and microcrystals. Theoretical calculations and powder X-ray diffraction experiments reveal that the switchable emission of DPD originated from the change of the distribution and the spatial arrangement of the frontier molecular orbitals, and the different stacking modes of DPD in microcrystals also contribute to the switchable emission of DPD in aggregates. PMID- 26278079 TI - Structural Evolution of Supercritical CO2 across the Frenkel Line. AB - Here, we study structural properties of the supercritical carbon dioxide and discover the existence of persistent medium-range order correlations, which make supercritical carbon dioxide nonuniform and heterogeneous on an intermediate length scale. We report on the CO2 heterogeneity shell structure where, in the first shell, both carbon and oxygen atoms experience gas-like-type interactions with short-range order correlations while within the second shell, oxygen atoms essentially exhibit a liquid-like type of interactions due to localization of transverse-like phonon packets. Importantly, we highlight a catalytic role of atoms inside of the nearest-neighbor heterogeneity shell in providing a mechanism for diffusion and proving the existence of an additional thermodynamic boundary in the supercritical carbon dioxide on an intermediate length scale. Finally, we discuss important implications for answering the intriguing question whether Venus may have had CO2 oceans and urge for an experimental detection of this persistent local-order heterogeneity. PMID- 26278080 TI - Efficient Planar Heterojunction Perovskite Solar Cells Based on Formamidinium Lead Bromide. AB - The development of medium-bandgap solar cell absorber materials is of interest for the design of devices such as tandem solar cells and building-integrated photovoltaics. The recently developed perovskite solar cells can be suitable candidates for these applications. At present, wide bandgap alkylammonium lead bromide perovskite absorbers require a high-temperature sintered mesoporous TiO2 photoanode in order to function efficiently, which makes them unsuitable for some of the above applications. Here, we present for the first time highly efficient wide bandgap planar heterojunction solar cells based on the structurally related formamidinium lead bromide. We show that this material exhibits much longer diffusion lengths of the photoexcited species than its methylammonium counterpart. This results in planar heterojunction solar cells exhibiting power conversion efficiencies approaching 7%. Hence, formamidinium lead bromide is a strong candidate as a wide bandgap absorber in perovskite solar cells. PMID- 26278081 TI - Silicon-Chip-Based Dielectric Spectroscopy for Conductivity and Molecular Dynamics Studies of Organic Films. AB - Interdigital electrodes fabricated by standard lithography on silicon chips are employed to probe the dipolar molecular dynamics and electric conduction properties of thin rhodamine films grown with two different methods. The conductivity is due to electronic charge carriers, and at around room temperature, it is higher by 1 order of magnitude in solution-deposited films than in thermally evaporated ones. The organic material exhibits two intrinsic dynamic processes, of which the one at higher temperature is due to the orientational motion of the dipole moment of the rhodamine units, while the one at lower temperature is due to the motion of a local dipole associated with the chlorine counterions and is absent in thermally evaporated films. Our results show that thin-film dielectric spectroscopy is an easily implementable and versatile tool to extract valuable information on thin organic films. PMID- 26278082 TI - Colloidal Quantum Dot Light-Emitting Diodes Employing Phosphorescent Small Organic Molecules as Efficient Exciton Harvesters. AB - Nonradiative energy transfer (NRET) is an alternative excitation mechanism in colloidal quantum dot (QD) based electroluminescent devices (QLEDs). Here, we develop hybrid highly spectrally pure QLEDs that facilitate energy transfer pumping via NRET from a phosphorescent small organic molecule-codoped charge transport layer to the adjacent QDs. A partially codoped exciton funnelling electron transport layer is proposed and optimized for enhanced QLED performance while exhibiting very high color purity of 99%. These energy transfer pumped hybrid QLEDs demonstrate a 6-fold enhancement factor in the external quantum efficiency over the conventional QLED structure, in which energy transfer pumping is intrinsically weak. PMID- 26278083 TI - Mapping the Vibronic Structure of a Molecule by Few-Cycle Continuum Two Dimensional Spectroscopy in a Single Pulse. AB - Accurate mapping of the electronic and vibrational structure of a molecular system is a basic goal of chemistry as it underpins reactivity and function. Experimentally, the challenge is to uncover the intramolecular interactions and ensuing dynamics that define this structure. Multidimensional coherent spectroscopy can map such interactions analogous to the way in which nuclear magnetic resonance provides access to the nuclear spin structure. Here we present two-dimensional coherent spectra measured using few-cycle continuum light. Critically, our approach instantaneously maps the energy landscape of a complex molecular system in a single laser pulse across 350 nm of bandwidth, thereby making it suitable for rapid molecular fingerprinting. We envision few-cycle supercontinuum spectroscopy based on the nonlinear optical response as a powerful tool to examine molecules in the condensed phase at the extremes of time, space, and energy. PMID- 26278084 TI - Fullerene-Free Polymer Solar Cells with Highly Reduced Bimolecular Recombination and Field-Independent Charge Carrier Generation. AB - Photogeneration, recombination, and transport of free charge carriers in all polymer bulk heterojunction solar cells incorporating poly(3-hexylthiophene) (P3HT) as donor and poly([N,N'-bis(2-octyldodecyl)-naphthelene-1,4,5,8 bis(dicarboximide)-2,6-diyl]-alt-5,5'-(2,2'-bithiophene)) (P(NDI2OD-T2)) as acceptor polymer have been investigated by the use of time delayed collection field (TDCF) and time-of-flight (TOF) measurements. Depending on the preparation procedure used to dry the active layers, these solar cells comprise high fill factors (FFs) of up to 67%. A strongly reduced bimolecular recombination (BMR), as well as a field-independent free charge carrier generation are observed, features that are common to high performance fullerene-based solar cells. Resonant soft X-ray measurements (R-SoXS) and photoluminescence quenching experiments (PQE) reveal that the BMR is related to domain purity. Our results elucidate the similarities of this polymeric acceptor with the superior recombination properties of fullerene acceptors. PMID- 26278085 TI - Excited State Dynamics of Ru10 Cluster Interfacing Anatase TiO2(101) Surface and Liquid Water. AB - Charge transfer dynamics at the interface of supported metal nanocluster and liquid water by GGA+U calculations combined with density matrix formalism is considered. The Ru10 cluster introduces new states into the band gap of TiO2 surface, narrows the band gap of TiO2, and enhances the absorption strength. The H2O adsorption significantly enhances the intensity of photon absorption, which is due to the formation of Ti-O(water) and Ru-O(water) bonds at the interfaces. The Ru10 cluster promotes the dissociation of water, facilitates charge transfer, and increases the relaxation rates of holes and electrons. We expect that our results are helpful in understanding basic processes contributing to photoelectrochemical water splitting. PMID- 26278086 TI - Reconstruction of the Molecular Structure of a Multichromophoric System Using Single-Molecule Defocused Wide-Field Imaging. AB - Single-molecule defocused wide-field imaging (DWFI) has been demonstrated to be useful to determine molecular structure parameters, such as the orientations of transition dipole moments and the angular relationships between chromophores in multichromophoric molecular systems. For a series of acetylene-linked perylene bisimide (PBI) macrocycles with different ring size comprising three to six PBI dyes, we reconstructed the molecular structure of the multichromophoric system using DWFI method. Furthermore, we revealed that the structural heterogeneities and distortions depend on the ring size. Our findings illustrate the use of DWFI to gain deeper insight into the structure-property relationships of artificial light-harvesting molecular systems. PMID- 26278087 TI - Electron Trap to Electron Storage Center in Specially Aligned Mn-Doped CdSe d Dot: A Step Forward in the Design of Higher Efficient Quantum-Dot Solar Cell. AB - Specially aligned surface-accumulated Mn-doped CdSe (MnCdSe) quantum dots (QDs) have been synthesized to study the effect of dopant atom on charge-carrier dynamics in QD materials. EPR studies suggest that the (4)T1 state of Mn(2+) lies above the conduction band of CdSe, and as a result no Mn-luminescence was observed from MnCdSe. Femtosecond transient absorption studies suggest that Mn atom introduces structural defects in surface-doped CdSe, which acts as electron trap center in doped QD for the photoexcited electron. Bromo-pyrogallol red (Br PGR) were found to form strong charge-trasfer complex with both CdSe and MnCdSe QDs. Charge separation in both the CdSe/Br-PGR and MnCdSe/Br-PGR composites was found to take place in three different pathways by transferring the photoexcited hole of CdSe/MnCdSe QDs to Br-PGR, electron injection from photoexcited Br-PGR to the QDs, and direct electron transfer from the HOMO of Br-PGR to the conduction band of both the QDs. Hole-transfer dynamics are found to be quite similar (~1.1 to 1.3 ps) for both of the systems and found to be independent of Mn doping. However, charge recombination dynamics was found to be much slower in the MnCdSe/Br-PGR system as compared with that in the CdSe/Br-PGR system, which confirms that the Mn dopant act as the electron storage center. As a consequence, the MnCdSe/Br-PGR system can be used as a better super sensitizer in quantum-dot sensitized solar cell to increase efficiency further. PMID- 26278088 TI - Chemical Instability of Dimethyl Sulfoxide in Lithium-Air Batteries. AB - Although dimethyl sulfoxide (DMSO) has emerged as a promising solvent for Li-air batteries, enabling reversible oxygen reduction and evolution (2Li + O2 <=> Li2O2), DMSO is well known to react with superoxide-like species, which are intermediates in the Li-O2 reaction, and LiOH has been detected upon discharge in addition to Li2O2. Here we show that toroidal Li2O2 particles formed upon discharge gradually convert into flake-like LiOH particles upon prolonged exposure to a DMSO-based electrolyte, and the amount of LiOH detectable increases with increasing rest time in the electrolyte. Such time-dependent electrode changes upon and after discharge are not typically monitored and can explain vastly different amounts of Li2O2 and LiOH reported in oxygen cathodes discharged in DMSO-based electrolytes. The formation of LiOH is attributable to the chemical reactivity of DMSO with Li2O2 and superoxide-like species, which is supported by our findings that commercial Li2O2 powder can decompose DMSO to DMSO2, and that the presence of KO2 accelerates both DMSO decomposition and conversion of Li2O2 into LiOH. PMID- 26278089 TI - Synthesis and Ultrafast Carrier Dynamics of Single-Crystal Two-Dimensional CuInSe2 Nanosheets. AB - We report, for the first time, the synthesis of single-crystal two-dimensional (2D) CuInSe2 nanosheets and the studies of ultrafast carrier dynamics and transport in this 2D material. Particularly, single-crystal 2D CuInSe2 with various thicknesses in the nanometer regime were fabricated by a solid-state chemical reaction between Cu and single-crystal exfoliated In2Se3 nanosheets. Characteristics of transient optical reflectivity, obtained from femtosecond optical pump-probe measurements on single CuInSe2 nanosheets, suggest that the hot carrier cooling process dominates the carrier dynamics within a few picoseconds following the optical excitation. Spatially resolved pump-probe measurements, coupled to simple model calculations, were used to obtain the ambipolar hot carrier diffusion coefficient in single nanosheets. The dependence of the hot carrier diffusion coefficient on the nanosheet thickness provides insight into the limiting mechanisms of hot carrier transport and can be used to gauge the possibility of efficient hot carrier collection in nanostructured CuInSe2 solar cells. PMID- 26278090 TI - Self-Alignment of the Methylammonium Cations in Thin-Film Organometal Perovskites. AB - A comparative study of the electronic structure of methylammonium (CH3NH3) in organometallic lead triiodide perovskite (CH3NH3PbI3) thin films synthesized using either one- or two-step deposition protocols is performed using angle resolved C K-edge soft X-ray absorption spectroscopy (XAS) and model calculations. We find that our XAS measurements can be accurately related to the ground-state unoccupied orbitals using a simple crystal field model. We further find that films made by the one-step deposition protocol exhibit angle-dependent features, indicating long-range alignment of the CH3NH3 molecules, although the angle-dependency decreases as the film thickness increases. No angle-dependency was observed in the films made via the two-step deposition method. PMID- 26278091 TI - Correlated Local Bending of a DNA Double Helix and Its Effect on DNA Flexibility in the Sub-Persistence-Length Regime. AB - Mechanical characteristics of DNA in the sub-persistence-length (lP ~ 150 base pairs) regime are vital to many of its biological functions but not well understood. Recent experimental studies in this regime have shown a dramatic departure from the traditional worm-like chain model, which is designed for long DNA chains and predicts a constant flexibility at all length scales. Here, we report an improved model with explicit considerations of a new length scale lD ~ 10 base pairs, over which DNA local bend angles are correlated. In this correlated worm-like chain model, a finite length correction term is analytically derived, and DNA flexibility is found to be contour-length-dependent. While our model reduces to the traditional worm-like chain model at length scales much larger than lP, it predicts that DNA becomes much more flexible at shorter sizes, in good agreement with recent cyclization measurements of short DNA fragments around 100 base pairs. PMID- 26278093 TI - What's in a Name? PMID- 26278092 TI - Chirality Discriminated by Heterodyne-Detected Vibrational Sum Frequency Generation. AB - We first demonstrated chiral vibrational sum frequency generation (VSFG) in the heterodyne detection, which enables us to uniquely determine chiral second-order nonlinear susceptibility consisting of phase and amplitude and distinguish molecular chirality with high sensitivity. Liquid limonene was measured to evaluate the heterodyne-detected chiral VSFG developed in this study. R-(+)- and S-(-)-limonene showed clearly opposite signs in the complex spectra of the second order nonlinear susceptibility in the CH stretching region. This is the first report of the chiral distinction by VSFG without any a priori knowledge about chiral and achiral spectral response. Furthermore, from the phase of the chiral VSFG field measured in the heterodyne detection, the origin of the chiral signal was ascribed to the bulk limonene. The heterodyne detection also improves detection limits significantly, allowing us to observe weak chiral signals in reflection. The heterodyne-detected chiral VSFG can provide information on absolute molecular configuration. PMID- 26278094 TI - Insights from Placing Photosynthetic Light Harvesting into Context. AB - Solar-energy conversion through natural photosynthesis forms the base of virtually all food chains on Earth and provides fiber, materials, and fuels, as well as inspiration for the design of biomimetic energy-conversion systems. We summarize well-known as well as recently discovered feedback loops between natural light-harvesting systems and whole-organism function in natural settings. We propose that the low effective quantum yield of natural light-harvesting systems in high light is caused by downstream limitations rather than unavoidable intrinsic vulnerabilities. We evaluate potential avenues, and their costs and benefits, for increasing the maximal rate and photon yield of photosynthesis in high light in plants and photosynthetic microbes. By summarizing mechanisms observable only in complex systems (whole plants, algae, or, in some cases, intact leaves), we aim to stimulate future research efforts on reciprocal feedback loops between light harvesting and downstream processes in whole organisms and to provide additional arguments for the significance of research on photosynthetic light harvesting. PMID- 26278095 TI - Unveiling Two Electron-Transport Modes in Oxygen-Deficient TiO2 Nanowires and Their Influence on Photoelectrochemical Operation. AB - Introducing oxygen vacancies (VO) into TiO2 materials is one of the most promising ways to significantly enhance light-harvesting and photocatalytic efficiencies of photoelectrochemical (PEC) cells for water splitting among others. However, the nature of electron transport in VO-TiO2 nanostructures is not well understood, especially in an operating device. In this work, we use the intensity-modulated photocurrent spectroscopy technique to study the electron transport property of VO-TiO2 nanowires (NWs). It is found that the electron transport in pristine TiO2 NWs displays a single trap-limited mode, whereas two electron-transport modes were detected in VO-TiO2 NWs, a trap-free transport mode at the core, and a trap-limited transport mode near the surface. The considerably higher diffusion coefficient (Dn) of the trap-free transport mode grants a more rapid electron flow in VO-TiO2 NWs than that in pristine TiO2 NWs. This electron transport feature is expected to be common in other oxygen-deficient metal oxides, lending a general strategy for promoting the PEC device performance. PMID- 26278096 TI - Water Dynamics in Metal-Organic Frameworks: Effects of Heterogeneous Confinement Predicted by Computational Spectroscopy. AB - The behavior of water confined in MIL-53(Cr), a flexible metal-organic framework (MOF), is investigated through computational infrared spectroscopy. As the number of molecules adsorbed inside of the pores increases, the water OH stretch band of the linear infrared spectrum grows in intensity and approaches that of bulk water. To assess whether the water confined in MIL-53(Cr) becomes liquid-like, two-dimensional infrared spectra (2DIR) are also calculated. Confinement effects result in distinct chemical environments that appear as specific features in the 2DIR spectra. The evolution of the 2DIR line shape as a function of waiting time is well described in terms of the orientational dynamics of the water molecules, with chemical exchange cross peaks appearing at a time scale similar to the hydrogen bond rearrangement lifetime. The confining environment considerably slows the hydrogen bond dynamics relative to bulk as a result of the competition between water-framework and water-water interactions. PMID- 26278097 TI - Termination Dependence of Tetragonal CH3NH3PbI3 Surfaces for Perovskite Solar Cells. AB - We investigated the termination dependence of structural stability and electronic states of the representative (110), (001), (100), and (101) surfaces of tetragonal CH3NH3PbI3 (MAPbI3), the main component of a perovskite solar cell (PSC), by density functional theory calculations. By examining various types of PbIx polyhedron terminations, we found that a vacant termination is more stable than flat termination on all of the surfaces, under thermodynamic equilibrium conditions of bulk MAPbI3. More interestingly, both terminations can coexist especially on the more probable (110) and (001) surfaces. The electronic structures of the stable vacant and PbI2-rich flat terminations on these two surfaces largely maintain the characteristics of bulk MAPbI3 without midgap states. Thus, these surfaces can contribute to the long carrier lifetime actually observed for the PSCs. Furthermore, the shallow surface states on the (110) and (001) flat terminations can be efficient intermediates of hole transfer. Consequently, the formation of the flat terminations under the PbI2-rich condition will be beneficial for the improvement of PSC performance. PMID- 26278098 TI - Imaging and Analysis of Single Optically Trapped Gold Nanoparticles Using Spatial Modulation Spectroscopy. AB - The extinction cross sections and spectra of single nanoparticles can be directly measured by moving the particle in and out of a tightly focused laser beam. This technique, known as spatial modulation spectroscopy, yields detailed information about the size, shape, and environment of the particles. These experiments are typically done on particles immobilized on a substrate. Here we demonstrate for the first time the use of spatial modulation spectroscopy to interrogate single, optically trapped nanoparticles in solution. Gold nanoparticles as small as 15 nm were trapped and imaged. The experiments were performed by modulating the position of the probe laser beam while scanning it over the trapped particle with a galvo-scanning mirror system. This technique opens up the possibility of precisely measuring the optical properties of single nanoparticles in liquid environments, free from the influence of a surface. PMID- 26278099 TI - Dissociative Electron Attachment to Anthralin to Model Its Biochemical Reactions. AB - The antipsoriatic drug anthralin (dithranol) is known to be extensively accumulated inside mitochondria of keratinocytes and to interact with the electron flow of the respiratory chain. Primary products of the one-electron reduction of polyphenolic anthralin observed in vivo are its dehydrogenated anions, which are formed by H-atom abstraction. The same species are mainly generated at low electron energies by dissociative electron attachment (DEA) to anthralin molecules in vacuo. A likely mechanism for the biochemical transformations of anthralin under reductive conditions in vivo is hypothesized on the basis of its DEA properties. The involvement of excited electronic states generated by ultraviolet irradiation of skin is discussed. PMID- 26278100 TI - Comparative analysis of microbial community between different cathode systems of microbial fuel cells for denitrification. AB - Two types of cathodic biofilm in microbial fuel cells (MFC) were established for comparison on their performance and microbial communities. Complete autotrophic simultaneous nitrification and denitrification (SND) without organics addition was achieved in nitrifying-MFC (N-MFC) with a total nitrogen (TN) removal rate of 0.35 mg/(L.h), which was even higher than that in denitrifying-MFC (D-MFC) at same TN level. Integrated denaturing gradient gel electrophoresis analysis based on both 16S rRNA and nirK genes showed that Alpha-, Gammaproteobacteria were the main denitrifier communities. Some potential autotrophic denitrifying bacteria which can use electrons and reducing power from cathodes, such as Shewanella oneidensis, Shewanella loihica, Pseudomonas aeruginosa, Starkeya novella and Rhodopseudomonas palustris were identified and selectively enriched on cathode biofilms. Further, relative abundance of denitrifying bacteria characterized by nirK/16S ratios was much higher in biofilm than suspended sludge according to real-time polymerase chain reaction. The highest enrichment efficiency for denitrifiers was obtained in N-MFC cathode biofilms, which confirmed autotrophic denitrifying bacteria enrichment is the key factor for a D-MFC system. PMID- 26278101 TI - A Pilot Study of a Computerized Decision Support System to Detect Invasive Fungal Infection in Pediatric Hematology/Oncology Patients. AB - OBJECTIVE: Computerized decision support systems (CDSSs) can provide indication specific antimicrobial recommendations and approvals as part of hospital antimicrobial stewardship (AMS) programs. The aim of this study was to assess the performance of a CDSS for surveillance of invasive fungal infections (IFIs) in an inpatient hematology/oncology cohort. METHODS: Between November 1, 2012, and October 31, 2013, pediatric hematology/oncology inpatients diagnosed with an IFI were identified through an audit of the CDSS and confirmed by medical record review. The results were compared to hospital diagnostic-related group (DRG) coding for IFI throughout the same period. RESULTS: A total of 83 patients were prescribed systemic antifungals according to the CDSS for the 12-month period. The CDSS correctly identified 19 patients with IFI on medical record review, compared with 10 patients identified by DRG coding, of whom 9 were confirmed to have IFI on medical record review. CONCLUSIONS: CDSS was superior to diagnostic coding in detecting IFI in an inpatient pediatric hematology/oncology cohort. The functionality of CDSS lends itself to inpatient infectious diseases surveillance but depends on prescriber adherence. PMID- 26278102 TI - Changes in Conjunctival Hemodynamics Predict Albuminuria in Sickle Cell Nephropathy. AB - BACKGROUND: Albuminuria is an early manifestation of deterioration in renal function in subjects with sickle cell disease (SCD). Hyperfiltration may be an early mechanism for kidney damage in SCD. The purpose of the current study was to determine the association between conjunctival hemodynamics and albuminuria in SCD subjects with preserved glomerular filtration rate. METHODS: Conjunctival microcirculation imaging was performed to measure conjunctival diameter and axial blood velocity (V) in 35 SCD and 10 healthy control subjects. Albuminuria, defined as albumin excretion ratio (AER), was obtained from the medical charts. Based on the 95% CI of conjunctival V in control subjects (0.40-0.60 mm/s), SCD subjects were allocated to 3 groups: V1 <0.40 mm/s (n = 7), V2 of 0.40-0.60 mm/s (n = 18) and V3 >=0.60 mm/s (n = 10). RESULTS: Mean log(AER) measurements in the V1, V2 and V3 groups were 1.08 +/- 0.67, 1.39 +/- 0.59 and 2.00 +/- 0.91 mg/g creatinine, respectively, and followed a positive linear trend from the V1 to V3 groups (p = 0.01). By multivariate linear regression analysis, conjunctival V significantly correlated with albuminuria (p = 0.01) independent of age, blood pressure, alpha-thalassemia, hematocrit, white blood cell count and lactate dehydrogenase concentration. CONCLUSIONS: Increased conjunctival V is associated with albuminuria in SCD subjects. Assessment of conjunctival microvascular hemodynamics may improve our understanding of the pathophysiology and clinical management of sickle cell nephropathy. PMID- 26278103 TI - miR-590-3p Is a Novel MicroRNA in Myocarditis by Targeting Nuclear Factor Kappa-B in vivo. AB - OBJECTIVE: Nuclear factor kappa-B (NF-954;B)-induced inflammation leads to myocarditis and heart dysfunction. How microRNAs (miRNAs) contribute to this process is poorly defined. The aim of this study was to investigate whether miRNAs regulate NF-954;B-induced inflammation in experimental autoimmune myocarditis (EAM) in vivo. METHODS AND RESULTS: NF-954;B and its related proinflammatory genes, including interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a), were activated in EAM. Profiling of NF-954;B-related miRNAs revealed that miR-590-3p was strikingly reduced in EAM. We found IL-6-induced proinflammatory signaling via miR-590-3p reduction, p50 induction, NF-954;B activation and IL-6/TNF-a expression. Moreover, a luciferase reporter assay demonstrated that miR-590-3p directly interacted with the 3' UTR (untranslated region) of the p50 subunit, and that miR-590-3p overexpression inhibited p50 expression. Finally, miR-590-3p transfection through adeno-associated virus significantly inhibited p50 expression, suppressed NF-954;B activity and blocked IL-6/TNF-a expression in vivo, reducing the lesion area and improving cardiac function in EAM. CONCLUSION: miR-590-3p is a novel NF-954;B-related miRNA that directly targets the p50 subunit. This may provide a novel strategy for the treatment of myocarditis. PMID- 26278104 TI - An orthotopic xenograft model with survival hindlimb amputation allows investigation of the effect of tumor microenvironment on sarcoma metastasis. AB - Overall survival rates for pediatric high-grade sarcoma have improved greatly in the past few decades, but prevention and treatment of distant metastasis remain the most compelling problems facing these patients. Traditional preclinical mouse models have not proven adequate to study the biology and treatment of spontaneous distant sarcoma metastasis. To address this deficit, we developed an orthotopic implantation/amputation model in which patient-derived sarcoma xenografts are surgically implanted into mouse hindlimbs, allowed to grow, then subsequently amputated and the animals observed for development of metastases. NOD/SCID/IL 2Rgamma-null mice were implanted with either histologically intact high grade sarcoma patient-derived xenografts or cell lines in the pretibial space and affected limbs were amputated after tumor growth. In contrast to subcutaneous flank tumors, we were able to consistently detect spontaneous distant spread of the tumors using our model. Metastases were seen in 27-90 % of animals, depending on the xenograft, and were repeatable and predictable. We also demonstrate the utility of this model for studying the biology of metastasis and present preliminary new insights suggesting the role of arginine metabolism and macrophage phenotype polarization in creating a tumor microenvironment that facilitates metastasis. Subcutaneous tumors express more arginase than inducible nitric oxide synthase and demonstrate significant macrophage infiltration, whereas orthotopic tumors express similar amounts of inducible nitric oxide synthase and arginase and have only a scant macrophage infiltrate. Thus, we present a model of spontaneous distant sarcoma metastasis that mimics the clinical situation and is amenable to studying the biology of the entire metastatic cascade. PMID- 26278105 TI - The Sexualized Girl: A Within-Gender Stereotype Among Elementary School Children. AB - Two studies (conducted in 2013) examined whether elementary-aged children endorse a within-gender stereotype about sexualized girls. In Study 1, children (N = 208) ages 6-11 rated sexualized girls as more popular but less intelligent, athletic, and nice compared to nonsexualized girls. These distinctions were stronger for girls and older children, and in accordance with our developmental intergroup theoretical framework, were related to children's cognitive development and media exposure. Study 2 (N = 155) replicated the previous findings using more ecologically valid and realistic images of girls and further explored individual differences in the endorsement of the sexualized girl stereotype. Additional results indicated that the belief that girls should be appearance focused predicted their endorsement of the sexualized girl stereotype. PMID- 26278107 TI - Response to Elia et al. 'Tauroursodeoxycholic acid in the treatment of patients with amyotrophic lateral sclerosis'. PMID- 26278106 TI - DNAJC13 p.Asn855Ser mutation screening in Parkinson's disease and pathologically confirmed Lewy body disease patients. AB - BACKGROUND: Recently, a novel mutation in exon 24 of DNAJC13 gene (p.Asn855Ser, rs387907571) has been reported to cause autosomal dominant Parkinson's disease (PD) in a multi-incident Mennonite family. METHODS: In the present study the mutation containing exon of the DNAJC13 gene has been sequenced in a Caucasian series consisting of 1938 patients with clinical PD and 838 with pathologically diagnosed Lewy body disease (LBD). RESULTS: Our sequence analysis did not identify any coding variants in exon 24 of DNAJC13. Two previously described variants in intron 23 (rs200204728 and rs2369796) were observed. CONCLUSION: Our results indicate that the region surrounding the DNAJC13 p.Asn855Ser substitution is highly conserved and mutations in this exon are not a common cause of PD or LBD among Caucasian populations. PMID- 26278108 TI - Reply to Dr Michaud et al. PMID- 26278111 TI - Dynamic path analysis - a useful tool to investigate mediation processes in clinical survival trials. AB - When it comes to clinical survival trials, regulatory restrictions usually require the application of methods that solely utilize baseline covariates and the intention-to-treat principle. Thereby, much potentially useful information is lost, as collection of time-to-event data often goes hand in hand with collection of information on biomarkers and other internal time-dependent covariates. However, there are tools to incorporate information from repeated measurements in a useful manner that can help to shed more light on the underlying treatment mechanisms. We consider dynamic path analysis, a model for mediation analysis in the presence of a time-to-event outcome and time-dependent covariates to investigate direct and indirect effects in a study of different lipid-lowering treatments in patients with previous myocardial infarctions. Further, we address the question whether survival in itself may produce associations between the treatment and the mediator in dynamic path analysis and give an argument that because of linearity of the assumed additive hazard model, this is not the case. We further elaborate on our view that, when studying mediation, we are actually dealing with underlying processes rather than single variables measured only once during the study period. This becomes apparent in results from various models applied to the study of lipid-lowering treatments as well as our additionally conducted simulation study, where we clearly observe that discarding information on repeated measurements can lead to potentially erroneous conclusions. PMID- 26278110 TI - Morphological and molecular changes in the murine placenta exposed to normobaric hypoxia throughout pregnancy. AB - Chronic hypoxia is a common complication of pregnancy, arising through malperfusion of the placenta or pregnancy at high altitude. The present study investigated the effects of hypoxia on the growth of the placenta, which is the organ that interfaces between the mother and her fetus. Mice were housed in an hypoxic environment for the whole of gestation. An atmosphere of 13% oxygen induced fetal growth restriction (1182 +/- 9 mg, n = 90 vs. 1044 +/- 11 mg, n = 62, P < 0.05) but enhanced placental weight (907 +/- 11 mg, n = 90 vs. 998 +/- 15 mg, n = 62,P < 0.05). Stereological analyses revealed an increase in the volume of maternal blood spaces in the placenta, consistent with increased flow. At the molecular level, we observed activation of the protein kinase B (Akt)-mechanistic target of rapamycin growth and proliferation pathway. Chronic hypoxia also triggered mild endoplasmic reticulum stress, a conserved homeostatic response that mediates translational arrest through phosphorylation of eukaryotic initiation factor 2 subunit alpha. Surprisingly, although subunits of the mitochondrial electron transport chain complexes were reduced at the protein level, there was no evidence of intracellular energy depletion. Finally, we demonstrated sex-specific placental responses to chronic hypoxia. Placentas from male fetuses were heavier (1082 +/- 2 mg, n = 30 vs. 928 +/- 2 mg, n = 34, P < 0.05) and less susceptible to hypoxia-induced oxidative stress than those from females. Their capacity to adapt may explain why male fetuses were significantly less growth restricted at embryonic day 18.5 than their female counterparts. These findings are consistent with the concept that male fetuses are more aggressive with respect to their nutrient demands, which may place them at greater risk of adverse outcomes under limiting conditions. PMID- 26278113 TI - Dehydrogenative Carbon-Carbon Bond Formation Using Alkynyloxy Moieties as Hydrogen-Accepting Directing Groups. AB - In the presence of a catalyst system consisting of Pd(OAc)2 , PCy3 , and Zn(OAc)2 , the reaction of alkynyl aryl ethers with bicycloalkenes, alpha,beta-unsaturated esters, or heteroarenes results in the site-selective cleavage of two C-H bonds followed by the formation of C-C bonds. In all cases, the alkynyloxy group acts as a directing group for the activation of an ortho C-H bond and as a hydrogen acceptor, thus rendering the use of additives such as an oxidant or base unnecessary. PMID- 26278112 TI - Aryl hydrocarbon receptor knockout rats are insensitive to the pathological effects of repeated oral exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. AB - Sustained activation of the aryl hydrocarbon receptor (AHR) is believed to be the initial key event in AHR receptor-mediated tumorigenesis in the rat liver. The role of AHR in mediating pathological changes in the liver prior to tumor formation was investigated in a 4-week, repeated-dose study using adult female wild-type (WT) and AHR knockout (AHR-KO) rats treated with 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). Beginning at 8 weeks of age, AHR-KO and WT rats were dosed by oral gavage with varying concentrations of TCDD (0, 3, 22, 100, 300 and 1000 ng kg(-1) day(-1) ). Lung, liver and thymus histopathology, hematology, serum chemistry and the distribution of TCDD in liver and adipose tissue were examined. Treatment-related increases in the severity of liver and thymus pathology were observed in WT, but not AHR-KO rats. In the liver, these included hepatocellular hypertrophy, bile duct hyperplasia, multinucleated hepatocytes and inflammatory cell foci. A loss of cellularity in the thymic cortex and thymic atrophy was observed. Treatment-related changes in serum chemistry parameters were also observed in WT, but not AHR-KO rats. Finally, dose dependent accumulation of TCDD was observed primarily in the liver of WT rats and primarily in the adipose tissue of AHR-KO rats. The results suggest that AHR activation is the initial key event underlying the progression of histological effects leading to liver tumorigenesis following TCDD treatment. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26278114 TI - Nonfunctional intra- and suprasellar tumor in a patient with visual disturbance and panhypopituitarism. PMID- 26278115 TI - Comparison of atherogenic risk factors among poorly controlled and well controlled adolescent phenylketonuria patients. AB - BACKGROUND: Previous studies investigating the known risk factors of atherosclerosis in phenylketonuria patients have shown conflicting results. The primary aim of our study was to investigate the serum atherogenic markers in adolescent classical phenylketonuria patients and compare these parameters with healthy peers. The secondary aim was to compare these atherogenic markers in well controlled and poorly controlled patients. METHODS: A total of 59 patients (median age: 12.6 years, range: 11-17 years) and 44 healthy controls (median age: 12.0 years, range: 11-15 years) were enrolled in our study. Phenylketonuria patients were divided into two groups: well-controlled (serum phenylalanine levels below 360 umol/L; 24 patients) and poorly controlled patients (serum phenylalanine levels higher than 360 umol/L). RESULTS: The mean high-density lipoprotein cholesterol levels of well-controlled patients (1.0+/-0.2 mmol/L) were significantly lower compared with poorly controlled patients and controls (1.1+/-0.2 mmol/L, p=0.011 and 1.4+/-0.2 mmol/L, p<0.001, respectively). Poorly controlled patients had lower high-density lipoprotein cholesterol levels than healthy controls (p=0.003). Homocysteine levels of both well-controlled (9.8+/ 6.4 umol/L) and poorly controlled (9.2+/-5.6 umol/L) patients were higher compared with controls (5.8+/-1.8 umol/L, p<0.01). The mean platelet volume of well-controlled patients (9.5+/-1.1 fL) was higher than that of poorly controlled patients and controls (8.9+/-0.8 fL, p=0.024 and 7.7+/-0.6 fL, p<0.001, respectively). CONCLUSION: Lower high-density lipoprotein cholesterol and higher homocysteine and mean platelet volume levels were detected in phenylketonuria patients. In particular, these changes were more prominent in well-controlled patients. We conclude that phenylketonuria patients might be at risk for atherosclerosis, and therefore screening for atherosclerotic risk factors should be included in the phenylketonuria therapy and follow-up in addition to other parameters. PMID- 26278117 TI - Application of Thoracoscopic Hybrid Surgery in the Treatment of Stage III Tuberculous Empyema. AB - BACKGROUND: To investigate the efficacy and value of thoracoscopic hybrid surgery in the treatment of stage III chronic tuberculous empyema (CTE). METHODS: 48 patients diagnosed as CTE with pleural thickening and encysted abscess cavity from were treated by hybrid operation (HO). Small incision operation was first used for resection of thickening pleural fibreboard and decortication of parietal pleura. Then, thoracoscopy was guided into chest to decorticate the visceral pleurali. Additional 25 patients with open operation of pleurectomy were set as control. RESULTS: The average operation time of HO group was 70 +/- 22 min compared to 130 +/- 32 min of control. The amount of bleeding, hospitalization time and chest tube drainage of HO group (200 +/- 55 ml, 18 +/- 1.2 days, 3.5 +/- 1.5 days) were significantly decreased compared to control (400 +/- 45 ml, 28 +/- 4.5 days, 6.5 +/- 2.5 days). Post operation complications occurred in 5 (10.42%) and 3 (12%) cases for HO group and control, respectively. CONCLUSIONS: In stage III CTE, the small incision assisted thoracoscopic hybrid surgery help to remove thickening parietal pleura, promote the application of thoracoscopy, which has obvious advantages compared to traditional surgery. PMID- 26278118 TI - Multivariate analysis of single-sweep evoked brain potentials for pharmaco electroencephalography. AB - BACKGROUND AND AIMS: Current findings on altered evoked potentials (EPs) caused by morphine are based on common alterations for a group of subjects after drug administration. However, this ignores the analysis of individual responses, which may explain the clinical differences in efficacy. Therefore, we explored the individual responses to morphine in terms of the altered single-sweep characteristics in a placebo-controlled crossover study. To account for multifactorial mechanisms, several characteristics were assessed simultaneously by multivariate pattern analysis (MVPA). METHODS: EPs were recorded from 62 channels and obtained before and after morphine and placebo administration during repeated electrical stimulations of the oesophagus in 12 healthy males. Additionally, the pain detection threshold was recorded to reflect the subjective analgesic effect in each subject. The characteristics of the sweeps were extracted by a multivariate matching pursuit algorithm with Gabor atoms implemented with a variable amplitude and constant phase across the sweeps. The single-sweep amplitudes were used as input to an MVPA algorithm to discriminate individual responses. The accuracy of the MVPA for each individual subject was used for correlation analysis of the analgesic effect. RESULTS: The mean classification accuracy when discriminating pre- and posttreatment morphine responses was 72% (p = 0.01). The individual classification accuracy was positively correlated to the analgesic effect of morphine (p = 0.03). Furthermore, the 2 posttreatment responses were classified and validated by the classification of the 2 pretreatment responses (p = 0.001). CONCLUSIONS: The alterations in the single-sweep EPs after morphine reflect the analgesic effect. The MVPA approach is a novel methodology for monitoring the individual efficacy of analgesics. PMID- 26278116 TI - Prospective evaluation of the fetal heart using Fetal Intelligent Navigation Echocardiography (FINE). AB - OBJECTIVE: To evaluate prospectively the performance of Fetal Intelligent Navigation Echocardiography (FINE) applied to spatiotemporal image correlation (STIC) volume datasets of the normal fetal heart. METHODS: In all women between 19 and 30 weeks' gestation with a normal fetal heart, an attempt was made to acquire STIC volume datasets of the apical four-chamber view if the following criteria were met: (1) fetal spine located between 5- and 7-o'clock positions; (2) minimal or absent shadowing (including a clearly visible transverse aortic arch); (3) absence of fetal breathing, hiccups, or movement; and (4) adequate image quality. Each STIC volume successfully acquired was evaluated by STICLoopTM to determine its appropriateness before applying the FINE method. Visualization rates of fetal echocardiography views using diagnostic planes and/or Virtual Intelligent Sonographer Assistance (VIS-Assistance(r)) were calculated. RESULTS: One or more STIC volumes (365 in total) were obtained successfully in 72.5% (150/207) of women undergoing ultrasound examination. Of the 365 volumes evaluated by STICLoop, 351 (96.2%) were considered to be appropriate. From the 351 STIC volumes, only one STIC volume per patient (n = 150) was analyzed using the FINE method, and consequently nine fetal echocardiography views were generated in 76-100% of cases using diagnostic planes only, in 98-100% of cases using VIS-Assistance only, and in 98-100% of cases when using a combination of diagnostic planes and/or VIS-Assistance. CONCLUSIONS: In women between 19 and 30 weeks' gestation with a normal fetal heart undergoing prospective sonographic examination, STIC volumes can be obtained successfully in 72.5% of cases. The FINE method can be applied to generate nine standard fetal echocardiography views in 98-100% of these cases using a combination of diagnostic planes and/or VIS Assistance. This suggests that FINE could be implemented in fetal cardiac screening programs. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. PMID- 26278120 TI - Frequency of Administration of Erythropoiesis-Stimulating Agents for the Anaemia of End-Stage Kidney Disease in Dialysis. PMID- 26278121 TI - Case of immunoglobulin M nephropathy in a patient with neurofibromatosis type 1. PMID- 26278122 TI - Rituximab can induce remission of nephrotic syndrome in the absence of peripheral B-cells. PMID- 26278123 TI - Membranous nephropathy and central retinal vein occlusion. PMID- 26278124 TI - A Randomized Comparative Study of Oral Corticosteroid Minipulse and Low-Dose Oral Methotrexate in the Treatment of Unstable Vitiligo. AB - BACKGROUND: Despite continued progress towards elucidation of the biochemical, genetic and immunopathological pathways in vitiligo, a definitive cure remains elusive. The initial therapy must be directed to arrest disease progression. Oral minipulse therapy (OMP) with betamethasone/dexamethasone has been tried and shown to be an effective modality to arrest the disease progression in vitiligo. OBJECTIVES: Methotrexate (MTX) is a time-tested effective treatment extensively used in various autoimmune disorders with good efficacy, safety and tolerability on a long-term basis. We intended to compare the efficacy of MTX with that of OMP in patients with unstable vitiligo vulgaris. PATIENTS AND METHODS: In a prospective randomized open label study, 52 patients with vitiligo were divided into two groups. Patients in group 1 received 10 mg methotrexate weekly. Group 2 patients received corticosteroid OMP which comprised tablets of dexamethasone 2.5 mg (5 tablets), taken on 2 consecutive days in a week (total weekly dose of 5 mg dexamethasone). RESULTS: In the MTX group, among 25 patients analyzed, during the course of treatment for 24 weeks, overall 6 patients developed new vitiliginous lesions. In the OMP group, 7/25 patients developed new lesions. Statistical correlation between the two groups showed no significance in the number of patients who developed new lesions (increasing disease activity) in either of the groups. At the end of the study, it was demonstrated that patients in both groups had a similar reduction in the vitiligo disease activity score. CONCLUSION: Our study demonstrated that both drugs are equally effective in controlling the disease activity of vitiligo. MTX can be used in patients with active vitiligo, wherever corticosteroids are contraindicated. PMID- 26278125 TI - New Treatments for Idiopathic Pulmonary Fibrosis: 'Die Another Day' if Diagnosed Early? PMID- 26278126 TI - Bilateral Truncal Ligation of the Inferior Thyroid Artery during Bilateral Subtotal Thyroidectomy Causes a Decrease in Parathormone without Clinically Manifest Hypoparathyroidism: A Randomized Clinical Trial. AB - BACKGROUND: Bilateral truncal ligation (BTL) of the inferior thyroid artery (ITA) is frequently used during subtotal thyroidectomy to reduce the risk of post operative bleeding as well as to reduce the blood loss intra-operatively. However, its effect on parathyroid function has not been evaluated in relation to age, residual and resected thyroid volume. METHODS: A total of 83 patients were randomized to receive non-BTL or BTL. After bilateral resection, the residual thyroid tissue on each side was measured by intra-operative ultrasonography. Laboratory and clinical examinations were performed the day before operation, intra-operatively and on post-operative days 2 and 5. The primary outcome measure was the difference in intact parathormone (PTHi) on post-operative day 5. Secondary outcomes were laboratory-diagnosed hypocalcaemia or hypoparathyroidism and clinically manifest hypoparathyroidism, respectively. RESULTS: PTHi on post operative day 5 was significantly lower in the BTL group (29.4 vs. 34.7 ng/l in the non-BTL group, p = 0.033), especially in 61- to 80-year-old patients (0 vs. 7.91 ng/l, p = 0.029). The biggest decline in PTHi was found in the BTL group ( 14.067 ng/l PTH, p = 0.018) with a residual thyroid volume of 0.5-1.9 ml. There were two cases of asymptomatic hypoparathyroidism in each group (5.1 vs. 4.8%, respectively, p = 1.000). The only case of clinically manifest hypoparathyroidism was in a BTL group patient aged 64 years (2.4%, p = 1.000). CONCLUSION: BTL of the ITA during subtotal thyroidectomy causes a larger decrease in PTH but does not lead to a significantly higher rate of clinically manifest hypoparathyroidism. BTL of the ITA, age >61 years, and a very small thyroid remnant (<2 ml) may be risk factors for post-operative hypoparathyroidism. PMID- 26278127 TI - Safety climate in English general practices: workload pressures may compromise safety. AB - OBJECTIVES: Although most health care interactions in the developed world occur in general practice, most of the literature on patient safety has focused on secondary care services. To address this issue, we have constructed a patient safety toolkit for English general practices. We report how practice and respondent characteristics affect scores on our safety climate measure, the PC Safequest, and address recent concerns with high levels of workload in English general practices. METHODS: We administered the PC-Safequest, a 30-item tool that was designed to measure safety climate in primary care practices, to 335 primary care staff members in 31 practices in England. Practice characteristics, such as list size and deprivation in the area the practice served, and respondent characteristics, such as whether the respondent was a manager, were also collected and used in a multilevel analysis to predict PC-Safequest scores. RESULTS: Managers gave their practices significantly higher safety climate scores than did non-managers. Respondents with more years of experience had a more negative perception of the level of workload in their practice. Practices with more registered patients and in areas of higher deprivation provided lower safety climate scores. CONCLUSIONS: Managers rated their practices more positively on our safety climate measure, so the differences between the perceptions of managers and other staff may need to be reduced in order to build a strong safety culture. Excessive workload for more experienced staff and lower safety climate scores for larger practices may reflect 'burnout'. Concerns that pressures in primary care could affect patient safety are discussed. PMID- 26278129 TI - The Clinical Utility of the Diagnostic Criteria for Psychosomatic Research: A Review of Studies. AB - BACKGROUND: The Diagnostic Criteria for Psychosomatic Research (DCPR) are a set of 12 psychosomatic syndromes and are provided with a reliable diagnostic structured interview. The DCPR have been proposed 20 years ago as an integrative assessment strategy that supplements the traditional psychiatric nosography for identifying patients within a given illness population whose psychosocial factors have clinical significance. This paper reviews their clinical utility, conceived as the degree and the amount of influence that the instrument has on multiple decisions and outcomes in clinical practice. METHODS: Published reports which involved the use of the DCPR were identified by searching electronic databases. Studies which best displayed the clinical utility of the DCPR system were then selected and reviewed. RESULTS: The DCPR system showed its clinical utility regarding the following clinical issues: (1) subtyping medical patients, (2) identifying subthreshold or undetected syndromes, (3) evaluating the burden of somatic syndromes, and (4) predicting treatment outcomes and identifying risk factors. CONCLUSIONS: The DCPR may help clinicians during the assessment process to recognize clinical conditions underlying symptom presentation, with important therapeutic and prognostic implications. PMID- 26278128 TI - Biological and protein-binding studies of newly synthesized polymer-cobalt(III) complexes. AB - The polymer-cobalt(III) complexes, [Co(bpy)(dien)BPEI]Cl3 . 4H2O (bpy = 2,2' bipyridine, dien = diethylentriamine, BPEI = branched polyethyleneimine) were synthesized and characterized. The interaction of these complexes with human serum albumin (HSA) and bovine serum albumin (BSA) was investigated under physiological conditions using various physico-chemical techniques. The results reveal that the fluorescence quenching of serum albumins by polymer-cobalt(III) complexes took place through static quenching. The binding of these complexes changed the molecular conformation of the protein considerably. The polymer cobalt(III) complex with x = 0.365 shows antimicrobial activity against several human pathogens. This complex also induces cytotoxicity against MCF-7 through apoptotic induction. However, further studies are needed to decipher the molecular mode of action of polymer-cobalt(III) complex and for its possible utilization in anticancer therapy. PMID- 26278130 TI - Need for improvements in clinical practice to retain patients in pre antiretroviral therapy care: Data from rural clinics in North West Province, South Africa. AB - We examined current challenges with patient engagement in HIV prevention and care in South Africa by assessing the procedures of eight public health clinics in the North West Province. Procedures consisted of (1) an inventory/audit of the HIV Counseling and Testing, pre-antiretroviral therapy (pre-ART), and antiretroviral therapy (ART) patient registers; (2) extraction of data from a convenience sample of 39 HIV-positive patient files; and (3) 13 key informant interviews with clinic staff to characterize retention and re-engagement practices for patients. Incomplete registers revealed little evidence of follow-up services, particularly for pre-ART patients. The more detailed examination of patient files indicated substantial disparities in the proportion of pre-ART versus ART patients retained in care. Key informant interviews contextualized the data, with providers describing multiple procedures for tracking and ensuring service delivery for ART patients and fewer procedures to retain pre-ART patients. These findings suggest that enhanced strategies are needed for ensuring continued engagement in HIV care, with a particular emphasis on improving the retention of pre-ART patients. The preventive benefits of ART scale-up may not be achieved if improvements are not made in the proportion of earlier-stage HIV-positive patients who are successfully engaged in care. PMID- 26278131 TI - Secreted biofilm factors adversely affect cellular wound healing responses in vitro. AB - Although most chronic wounds possess an underlying pathology, infectious agents also contribute. In many instances, pathogens exist as biofilms forming clusters surrounded by a secreted extracellular substance. We hypothesized that compounds secreted by biofilm bacteria may inhibit normal wound healing events including cell proliferation and migration. Conditioned media from two common bacterial species associated with chronic skin wounds and chronic tympanic membrane perforations, Staphylococcus aureus and Pseudomonas aeruginosa, were evaluated for their capacity to affect keratinocyte proliferation and migration. Additionally, proteomic analysis was performed to identify proteins within the biofilm conditioned media that may contribute to these observed effects. Biofilm conditioned media from both species inhibited proliferation in human tympanic membrane derived keratinocytes, whereas only biofilm conditioned media from S. aureus inhibited migration. Human epidermal keratinocytes were found to be more sensitive to the effects of the conditioned media resulting in high levels of cell death. Heat treatment and microfiltration suggested that S. aureus activity was due to a protein, while P. aeruginosa activity was more likely due to a small molecule. Proteomic analysis identified several proteins with putative links to delayed wound healing. These include alpha hemolysin, alcohol dehydrogenase, fructose-bisphosphate aldolase, lactate dehydrogenase and epidermal cell differentiation inhibitor. PMID- 26278132 TI - Examining the role of different age groups, and of vaccination during the 2012 Minnesota pertussis outbreak. AB - There is limited information on the roles of different age groups during pertussis outbreaks. Little is known about vaccine effectiveness against pertussis infection (both clinically apparent and subclinical), which is different from effectiveness against reportable pertussis disease, with the former influencing the impact of vaccination on pertussis transmission in the community. For the 2012 pertussis outbreak in Minnesota, we estimated odds ratios for case counts in pairs of population groups before vs. after the epidemic's peak. We found children aged 11-12y, 13-14y and 8-10y experienced the greatest rates of depletion of susceptible individuals during the outbreak's ascent, with all ORs for each of those age groups vs. groups outside this age range significantly above 1, with the highest ORs for ages 11-12y. Receipt of the fifth dose of DTaP was associated with a decreased relative role during the outbreak's ascent compared to non-receipt [OR 0.16 (0.01, 0.84) for children aged 5, 0.13 (0.003, 0.82) for ages 8-10y, indicating a protective effect of DTaP against pertussis infection. No analogous effect of Tdap was detected. Our results suggest that children aged 8-14y played a key role in propagating this outbreak. The impact of immunization with Tdap on pertussis infection requires further investigation. PMID- 26278133 TI - Bacterial floc mediated rapid streamer formation in creeping flows. AB - One of the central puzzles concerning the interaction of low Reynolds number fluid transport with bacterial biomass is the formation of filamentous structures called streamers. In this manuscript, we report our discovery of a new kind of low Re bacterial streamers, which appear from pre-formed bacterial flocs. In sharp contrast to the biofilm-mediated streamers, these streamers form over extremely small timescales (less than a second). Our experiments, carried out in a microchannel with micropillars rely on fluorescence microscopy techniques to illustrate that floc-mediated streamers form when a freely-moving floc adheres to the micropillar wall and gets rapidly sheared by the background flow. We also show that at their inception the deformation of the flocs is dominated by recoverable large strains indicating significant elasticity. These strains subsequently increase tremendously to produce filamentous streamers. Interestingly, we find that these fully formed streamers are not static structures and show viscous response at time scales larger than their formation time scales. Finally, we show that such novel streamer formation can lead to rapid clogging of microfluidic devices. PMID- 26278134 TI - Quantitative analysis of magnetic spin and orbital moments from an oxidized iron (1 1 0) surface using electron magnetic circular dichroism. AB - Understanding the ramifications of reduced crystalline symmetry on magnetic behavior is a critical step in improving our understanding of nanoscale and interfacial magnetism. However, investigations of such effects are often controversial largely due to the challenges inherent in directly correlating nanoscale stoichiometry and structure to magnetic behavior. Here, we describe how to use Transmission Electron Microscope (TEM) to obtain Electron Magnetic Circular Dichroism (EMCD) signals as a function of scattering angle to locally probe the magnetic behavior of thin oxide layers grown on an Fe (1 1 0) surface. Experiments and simulations both reveal a strong dependence of the magnetic orbital to spin ratio on its scattering vector in reciprocal space. We exploit this variation to extract the magnetic properties of the oxide cladding layer, showing that it locally may exhibit an enhanced orbital to spin moment ratio. This finding is supported here by both spatially and angularly resolved EMCD measurements, opening up the way for compelling investigations into how magnetic properties are affected by nanoscale features. PMID- 26278135 TI - Predicted versus measured resting energy expenditure in patients requiring home parenteral nutrition. AB - OBJECTIVES: Guidelines from the European Society for Clinical Nutrition and Metabolism (ESPEN) recommend between 20 and 35 kcal/kg daily for patients requiring home parenteral nutrition (PN). Other guidelines use predictive equations. However, these equations have not been validated. Indirect calorimetry is recommended as the gold standard for determining resting energy expenditure (REE). The aim of this study was to compare the frequently used equations with measured REE. METHODS: Seventy-six hospitalized patients suffering from intestinal failure (ages 21-85 y) were enrolled between January 2012 and May 2014. They were eligible for implementation of home parenteral nutrition (HPN) due to short bowel syndrome (54%), intestinal fistulae (24%), cancer obstruction (16%), and radiation-induced intestinal injury (6%). REE measurements were compared with predictive equations by Harris and Benedict (HB), Owen, Ireton Jones, and Mifflin, as well as recommendations from ESPEN. RESULTS: In all, 152 calorimetry measurements (two per patient) were performed in 76 patients, after total PN administrations. An average result of REE measurement by indirect calorimetry was 1181 +/- 322 kcal/d. Variability in momentary energy expenditure (MEE) from one measurement to the other was 8% +/- 7%. Bland-Altman analysis showed a mean bias of -192 +/- 300 kcal/d between MEE and estimated energy expenditure using the HB equation, which means that the equation increased the score on average by 192 +/- 300 kcal/d. Limits of agreement (LoA) between the two methods was -780 to +396 kcal/d. Estimation energy expenditure using the Ireton Jones equation gave a mean bias of -359 +/- 335 kcal/d. LoA between the two methods was -1015 to +297 kcal/d. For Owen equation, Bland-Altman analysis showed a mean bias of -208 +/- 313 kcal/d and the LoA between the two methods was -822 to +406 kcal/d. Using the Mifflin equation, estimation energy expenditure gave a mean bias of -172 +/- 312 kcal/d and the LoA between the two methods was -784 to +439 kcal/d. Using the ESPEN range (20-35 kcal/kg daily) analysis showed mean bias of -13 +/- 326 kcal/d and the LoA was -652 to +626 kcal/d for 20 kcal/kg daily and mean bias of -909 +/- 436 kcal/d with the LoA between the two methods 1764 to -54 kcal/d for 35 kcal/kg daily. CONCLUSION: If REE cannot be measured by indirect calorimetry in patients qualified for HPN, the Ireton-Jones equation and the 20 kcal/kg/d ESPEN recommendation seem to be the most appropriate ones as it provides results that constitute the best approximation of calorimetric examination results. PMID- 26278137 TI - Association of BCSC-1 with human esophageal squamous cell carcinoma. AB - Breast cancer suppressor candidate-1 (BCSC-1) is a newly identified candidate tumor suppressor gene. BCSC-1 shows decreased levels in a variety of cancer types. In this study, we investigated the association between BCSC-1 and human esophageal squamous cell carcinoma (ESCC). BCSC-1 expression was detected in ESCC and normal tissues adjacent to tumor tissues by Western blot analysis and real time PCR as well as immunohistochemistry of paraffin sections. The relationships between BCSC-1 expression and various clinicopathological characteristics were analyzed. Western blot analysis and real-time PCR showed that levels of BCSC-1 protein and mRNA expression in ESCC significantly decreased compared with those in adjacent normal tissues. Immunohistochemistry exhibited marked reduction of BCSC-1 in 38 of 105 ESCC specimens. Moreover, downregulation of BCSC-1 was associated with the grade of tumor cellular differentiation (P<0.05). These findings indicate that BCSC-1 downregulation in ESCC is associated with carcinogenesis and may play important roles during the process of ESCC cancer development. PMID- 26278138 TI - Improved outcome for children and adolescent with acute lymphoblastic leukemia in the first decade of the 21st century: A report from the Slovak Republic. AB - Our aim was to analyze event-free (EFS) and overall survival (OS) among children and adolescents with acute lymphoblastic leukemia (ALL) treated with International BFM Intercontinental trial (ALL IC 2002) therapy in the Slovak Republic. In total, 280 children and adolescent age 1 to 18 years were treated with ALL IC BFM 2002 based therapy from 2002 to 2012, which was divided into two periods. During 2002-2007, when patients were actively enrolled in the ALL IC-BFM 2002 trial, and during 2008-2012 when the trial was closed and patients were treated with the same therapy without randomization. Five-year EFS and OS rates were 79% (+/- 2.6%) and 86% (+/- 2.1%), respectively, similar to results obtained in the ALL-BFM 95 trial, which was the basis for ALL IC BFM 2002 therapy. The EFS (p<0.012) and OS (p<0.003) were significantly better than the prior Slovak experience in 1997-2001. Survival is improved in standard and intermediate risk groups, including those age 1 to 6 years, and older; with B-cell or T-cell immunophenotype, and is also excellent for those with good early response. The rate of death in induction, cumulative incidence of death in complete remission and of relapse decreased. However, outcome was suboptimal for patients in the high risk group. Current EFS and OS rates for children and adolescents with ALL in the Slovak Republic resembled those obtained in Western Europe as a result of clinical trial participation, and clinical experience acquired with intensive BFM type treatment. PMID- 26278136 TI - Histamine deficiency exacerbates myocardial injury in acute myocardial infarction through impaired macrophage infiltration and increased cardiomyocyte apoptosis. AB - Histamine is a biogenic amine that is widely distributed and has multiple functions, but the role it plays in acute myocardial infarction (AMI) remains unclear. In this study, we investigated the origin and contribution of endogenous histamine to AMI. Histidine decarboxylase (HDC) is the unique enzyme responsible for histamine generation. Using HDC-EGFP bacterial artificial chromosome (BAC) transgenic mice in which EGFP expression is controlled by the HDC promoter, we identified HDC expression primarily in CD11b(+)Gr-1(+) immature myeloid cells (IMCs) that markedly increase in the early stages of AMI. Deficiency of histamine in HDC knockout mice (HDC(-/-)) reduced cardiac function and exacerbated the injury of infarcted heart. Furthermore, administering either an H1 receptor antagonist (pyrilamine) or an H2 receptor antagonist (cimetidine) demonstrated a protective effect of histamine against myocardial injury. The results of in vivo and in vitro assays showed that histamine deficiency promotes the apoptosis of cardiomyocytes and inhibits macrophage infiltration. In conclusion, CD11b(+)Gr 1(+) IMCs are the predominant HDC-expressing sites in AMI, and histamine plays a protective role in the process of AMI through inhibition of cardiomyocyte apoptosis and facilitation of macrophage infiltration. PMID- 26278139 TI - Allogeneic stem cell transplantation after fludarabine, melphalan and thymoglobulin followed by early withdrawal of prophylactic immunosuppression could be an effective approach to patients with acute lymphoblastic leukemia. AB - Presented are results of allogeneic hematopoietic stem cell transplantations (HSCTs) in 13 patients with high-risk acute lymphoblastic leukemia (ALL) in the first complete remission after a reduced intensity conditioning combining fludarabine (150 mg/m2) and melphalan (140 mg/m2) with thymoglobulin (4.5 mg/kg). The immunosuppressive effect of T-cell depletion reducing the risk of graft versus-host disease (GVHD) and non-relapse mortality was compensated by early initiation of reduction and withdrawal of prophylactic immunosuppression aimed at maintaining effective immunological antileukemic control. The median post transplant follow-up was 23 (range, 10-65) months. Stable engraftment of donor's hematopoiesis was achieved in all patients. Acute GVHD was observed in two cases (15.4%); the chronic form was not noted. Two patients (15.4%) relapsed with ALL at 3 and 16 months after transplantation. During the above post-transplant follow up, all 13 recipients were alive, with a probability of 2-year disease-free survival of 76.9% (95% CI 51-100%). Although the results were obtained with a small pilot study group it may be assumed that, given the prognostic risk of most patients and the nearly 2-year median post-transplant follow-up, the approach may be considered as an alternative to HSCTs after traditional myeloablative or reduced conditioning regimens with standard GVHD prophylaxis. PMID- 26278140 TI - Factors influencing circulating MicroRNA level in the studies of hepatocellular carcinoma biomarker. AB - Factors influencing circulating miRNA as a diagnostic marker of hepatocellular carcinoma (HCC) are still unknown. We used two kits to extract total RNA of 90 paired serum and plasma samples of volunteers in different statuses including healthy, hepatitis, cirrhosis and HCC. U6, miR-183 and cel-miR-39 expression levels were detected by qRT-PCR. Calculate was the relative expression level of miR-183 and recovery of cel-miR-39 with 2-??CT method and standard curve method, respectively.MiRNeasy Serum/Plasma Kit was superior to miRcute miRNA Isolation Kit in the quality of the total RNA and the expression levels of U6 and miR-183, with recovery of external reference cel-miR-39 of the former in serum and plasma was the latter's 3.95-fold and 3.15-fold, respectively. The recovery of cel-miR 39 was significantly higher in serum than that in plasma in all groups except the HCC. But the trend of U6 expression of four groups in serum was different from that in plasma. There were significant differences in absorbance in 260nm, the ratio of absorbance in 260nm and 280nm (260/280), the ratio of absorbance 260nm and 230nm (260/230), the ct value of U6 and the recovery of cel-miR-39 among groups in serum or plasma. Sensitivity and specificity of miR-183 as a diagnostic marker of HCC were 57.9% and 76.2% in serum, and 78.9% and 81.0% in plasma, respectively.Caution should be taken when comparing miRNA data generated from different extraction kits, sample types or disease statuses in the study of miRNA as a diagnostic marker of HCC. PMID- 26278141 TI - Salvage chemotherapy in metastatic colorectal cancer with the combination of capecitabine and mitomycin C. AB - A significant proportion of heavily pretreated patients with metastatic colorectal cancer maintain good performance status (PS) and are eligible for further systemic treatment. Mitomycin C (MMC) combined with capecitabine can be considered as salvage treatment in this group of patients. To evaluate the efficacy and toxicity of mitomycin C and capecitabine as at least third-line systemic therapy (after failure of 5Fu, irinotecan, oxaliplatin-based chemotherapy regimens and targeted therapies) in patients with metastatic colorectal cancer. A total of 31 patients with a median age of 55.2 years with metastatic colorectal cancer received salvage chemotherapy at the Oncological Department of University Hospital in Krakow, Poland, between July 2011 and July 2014. Chemotherapy consisted of intravenous MMC 6 mg/m2 on day 1 and oral capecitabine 1000 mg/m2 twice daily on days 1-14 followed by a 7-day treatment free interval. Each cycle was repeated every 3 weeks unless there was evidence of disease progression or unacceptable toxicity. All the31 patients were evaluable for response and toxicity. A total of 113 cycles were administered. Five of the 31 (16.1%) patients had stable disease after three cycles of chemotherapy, 24 (77.4%) patients progressed and 1 (3.2%) patient is still undergoing treatment. One patient (3.2%) died due to cardiac infarct 5 days after starting treatment. Median progression free survival (PFS) was 2.5 months. Median overall survival (OS) was 4.9 months. Toxicity was mild and easily manageable. Mitomycin C and capecitabine can be considered as salvage therapy in heavily pretreated patients with metastatic colorectal cancer and with good performance status. Toxicity of these drugs combination is moderate and easily manageable. PMID- 26278142 TI - Outcomes of 167 healthy sibling donors after peripheral blood stem cell mobilization with G-CSF 16MUg/kg/day: efficacy and safety. AB - Mobilization of peripheral blood stem cells (PBSC) using the granulocyte colony stimulating factor (G-CSF) has enabled the collection even from older donors and those with comorbidities. Several clinical parameters have been reported to predict the success of PBSC mobilization. The aim of our study was to evaluate the safety of PBSC donation in a cohort of 167 sibling donors after mobilization with G-CSF 16 MUg/kg/day for 5 days during short- and long term follow-up and to analyse the efficacy, toxicity and factors influencing CD34+ mobilization capacity. All 167 sibling donors completed the established mobilization protocol. The median yield was 7.9x106 CD34 cells/kg per recipient weight. The optimal target dose of CD34 cells >= 4.0x106/kg was achieved in 140 donors (84%). Only in 4 donors (2%) was the CD34+ yield < 2x106/kg. No major toxicities occured.Factors associated with higher PBSC yields included age 51/MUL (p 45.5 x 109/L (p = 0.003). Comorbidity score, performance status and donor weight did not significantly influence PBSC yields. Long-term follow-up was possible in 60% (101/167) of the donors. The median length of follow-up from PBSC donation was 11.9 years. Most of these donors reported good or very good general health (91%), and no hematological malignancies were observed.The mobilization of PBSC in sibling donors with G-CSF 16 MUg/kg/day is an effective and safe procedure with no significant short- and long-term toxicities. PMID- 26278143 TI - Results and prognostic factors of 3-dimensional conformal radiotherapy and intensity-modulated radiotherapy for esophageal carcinoma. AB - The aim of this study was to summarize the outcomes and prognostic factors of 3 dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) for esophageal carcinoma in our institute. Five hundred ninety-two patients received radiotherapy for esophageal carcinoma (123 with 3D-CRT, 469 with IMRT) from January 2002 to March 2012. Three hundred sixty patients received radiotherapy alone and 232 patients received radiotherapy and chemotherapy. The endpoints were overall survival (OS), progression-free survival (PFS). Kaplan Meier analysis was used to calculate endpoints, the log-rank test for univariate analysis, and multivariate analysis to identify independent prognostic factors. The median follow-up time was 22.6 months and the median dose was 60 Gy. The 1 year OS, PFS were 65.3%, 52.1%; the 3-year OS, PFS were 34.0%, 28.0%; and the 5 year OS, PFS were 23.5%, 19.6%. The median OS was 20 months (95% CI: 17.9-22.1 months) and the median PFS was 14 months (95% CI: 11.8-16.2 months). Univariate analysis indicated that sex, N-stage, M-stage, TNM stage, radiotherapy dose, weight loss before treatment, smoking, and drinking affected OS and PFS (p < 0.05 for all). T-stage affected OS (p = 0.042), but no significant influence on PFS (p = 0.101). The independent prognostic factors for better OS and PFS were early clinical TNM stage, high radiotherapy dose, and female sex (p < 0.05 for all). The results of esophageal carcinoma patients treated with 3D-CRT and IMRT with or without chemotherapy were promising. Clinical TNM stage, radiotherapy dose and sex were the independent prognostic factors for OS and PFS. PMID- 26278144 TI - 53BP1 foci as a marker of tumor cell radiosensitivity. AB - Predicting tumor radiosensitivity has yet to be routinely integrated into radiotherapy. We analyzed the possibility to assess radiosensitivity of tumor cells based on endogenous and radiation-induced 53BP1 foci which are molecular markers of DNA double strand breaks (DSB). In eleven tumor cell lines of different origin, radiosensitivity was assessed by surviving cell fraction following irradiation with 2 Gy (SF2). 53BP1 foci were measured at 4 and 12 h post-irradiation by confocal laser microscopy and dedicated software. The correlation of 53BP1 foci and their post-irradiation kinetics with SF2 was assessed using Spearman rank test. The SF2 correlated with both excess of radiation-induced 53BP1 foci per cell at 4 h after irradiation and decay in number of 53BP1 foci from 4 to 12 h post-irradiation. The fraction of cells with multiple endogenous 53BP1 foci also correlated with SF2 of tumor cells. We conclude that the radiosensitivity of tumor cells can be predicted by kinetics of formation and decay of 53BP1 foci after irradiation. For the first time we report that the fraction of cells with multiple endogenous 53BP1 foci can be used as a marker of tumor cell radiosensitivity. PMID- 26278145 TI - Identification of genes in ulcerative colitis associated colorectal cancer based on centrality analysis of co-expression network. AB - PreviousColorectal cancer (CRC) is a well-recognized complication of Ulcerative colitis (UC) and patients with UC have a higher incidence of CRC than the general population. Early detection and mechanism of colitis-associated colorectal cancer (CAC) is still challenging. The aim of present study is to identify genes associated with CAC by centrality analysis of co-expression networks. Co expression networks of CRC and UC were constructed by empirical Bayes approach based on top 200 gene signatures which identified by the model of genome-wide relative significance and genome-wide global significance across multiple datasets. Centrality of degree, stress centrality, betweenness centrality and closeness centrality of co-expression networks were selected to explore hub genes presented in CRC and UC. Validation of mRNA expression in CRC patients was conducted by real-time quantitative Polymerase Chain Reaction (qPCR). Pathway analysis was conducted based on Kyoto Encyclopedia of Genes and Genomes database. We found 21 common genes, such as SLC4A4 and AQP8, both existed in CRC and UC top 200 genes. By accessing centralities analyses of co-expression networks, HPGD and AQP8 were common hub genes in CRC and UC, and various centralities analyses of the same gene were not consistent. Patients with alteration of AQP8 have significantly reduced the survival rate according to real-time qPCR results. Our study displayed genes associated with CAC (AQP8 and HPGD), and they might be reliable biomarkers for early detection and therapies of CAC. PMID- 26278146 TI - Downregulation of PLK1 by RNAi attenuates the tumorigenicity of esophageal squamous cell carcinoma cells via promoting apoptosis and inhibiting angiogenesis. AB - Polo-like kinase 1(PLK1) is essential for the maintenance of genomic stability during mitosis. PLK1 has been reported to be upregulated in several solid tumors, including esophageal squamous cell carcinoma (ESCC). However, the role of PLK1 in tumorigenesis of ESCC remains undetermined. We used siRNA and lentivirus-mediated PLK1 RNA interference to investigate the tumor suppressor function of PLK1 reduction in ESCC cells. Flow cytometry and Terminal deoxynuleotidyl transferase mediated nick-end labeling assay in vitro, as well as immunohistochemitry analysis of Caspase-3 and CD31 in s.c. tumor tissue section, were performed. Knock down of PLK1 expression significantly suppressed the ability of ESCC cells to form colonies in plastic and soft agar. PLK1 reduction mediated by lentivirus caused growth suppression of ESCC in nude mice. Caspase-3 upregulation further indicated that dysregulated apoptosis might contribute to reduced tumorigenecity. In particular, downregulation of CD31 suggested that PLK1 reduction-induced angiogenesis inhibition may also contribute, at least in part, to attenuated tumorigenecity. These findings indicate that PLK1 might play roles in tumorigenesis of ESCC and that PLK1 might be a potential gene therapy target in ESCC. Apoptosis induction together with decreased angiogenesis might be involved in the mechanism of tumor suppressor function of RNA interference targeting PLK1. PMID- 26278147 TI - Rapamycin-topotecan combination exhibited enhanced antitumor efficacy compared to topotecan used alone in cisplatin-resistant ovarian cancer cells. AB - The present study aimed to investigate the antitumor efficacy of combination of topotecan with rapamycin, a mTOR inhibitor, in cisplatin-resistant ovarian cancer cells A2780cis and COC1/DDP. Expressions of mTOR and its target molecules p70S6K and 4E-BP1 were determined in A2780cis and COC1/DDP and the parental cells A2780 and COC1 that are sensitive to cisplatin using Western blotting. Cell proliferation was examined using MTT assay in vitro and a nude mouse model in vivo, respectively. Cell apoptosis and the relevant proteins were determined by flow cytometry and Western blotting. We found that the levels of phosphorylated mTOR, p70S6K, and 4E-BP1 were obviously higher in A2780cis and COC1/DDP cells than that in A2780 and COC1 cells. Pretreatment with rapamycin significantly enhanced the effects of topotecan in suppressing cell proliferation and soliciting cell apoptosis in A2780cis and COC1/DDP cells. Cells that were sequentially exposed to rapamycin and topotecan had significantly higher levels of cleaved caspase-8, -3, and PARP compared to those treated with topotecan alone. Mice co-administered rapamycin and topotecan had significantly decreased terminal tumor burden without additional loss of bodyweight compared to the mice received topotecan alone. The results suggested that rapamycin sensitized A2780cis and COC1/DDP cells to topotecan-induced apoptosis and rapamycin topotecan combination might have a value in treatment of cisplatin-resistant ovarian cancer. PMID- 26278148 TI - Identification of potential therapeutic targets for melanoma using gene expression analysis. AB - Metastatic melanoma represents a significant cause of death in patients with melanoma and the frequency is increasing. The aim of this study was to identify potential therapeutic targets for metastatic melanoma. Gene expression profile GSE44660 was downloaded from Gene Expression Omnibus database. A total of 22 samples were analyzed in our study, including 3 specimens of normal melanocytes, 12 specimens of melanoma LNM (lymph node metastasis) and 7 specimens of MBM (melanoma brain metastasis). DEGs (differentially expressed genes) in LNM and MBM were identified respectively using Limma package. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways analyses of common DEGs between two comparison groups were performed using DAVID, followed by cancer related genes and transcription factor analysis. PPI (protein-protein interaction) network was constructed by STRING, and significant key genes were selected. Totally, 401 common DEGs were identified. Disease analysis showed that ICAM1 (intercellular adhesion molecule 1) and NBN (nibrin) were related to melanoma. In the PPI network, BIRC5 (baculoviral IAP repeat containing 5), BUB1 (BUB1 mitotic checkpoint serine/threonine kinase), GMNN (geminin, DNA replication inhibitor), AURKA (aurora kinase A), TOP2A (topoisomerase (DNA) II alpha) and BUB1B (BUB1 mitotic checkpoint serine/threonine kinase B) were with higher degree more than 50. ICAM1, NBN, BIRC5, BUB1, BUB1B, GMNN, AURKA and TOP2A may play key roles in the progression and development of melanoma. They may be used as specific therapeutic targets in the treatment of metastatic melanoma. However, further experiments are still needed to confirm our results. PMID- 26278149 TI - Influence of different chemical agents (H2O2, t-BHP and MMS) on the activity of antioxidant enzymes in human HepG2 and hamster V79 cells; relationship to cytotoxicity and genotoxicity. AB - We investigated activities of antioxidant enzymes (AEs), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) in human HepG2 and hamster V79 cells treated with a scale of concentrations of hydrogen peroxide (H2O2), tert-butyl hydroperoxide (t-BHP) and methyl methanesulfonate (MMS). Cytotoxicity and genotoxicity of these substances were evaluated simultaneously. We have found out that H2O2, t-BHP and MMS predictably induce significant concentration dependent increase of DNA lesions in both cell lines. Cytotoxicity detected in V79 cells with help of PE test was in a good conformity with the level of DNA damage. MTT test has proved unsuitable, except for MMS-treated V79 cells. Compared with human cells HepG2, hamster cells V79 manifested approximately similar levels of SOD and CAT but ten times higher activity of GPx. Across all concentrations tested the most significant increase of activity of the enzyme CAT was found in H2O2- and t-BHP-treated HepG2 cells, of the enzyme SOD in t-BHP- and MMS-treated V79 cells, and of the enzyme GPx in H2O2-treated V79 cells. We suggest that stimulation of enzyme activity by the relevant chemical compounds may result from transcriptional or post-transcriptional regulation of the expression of the genes CAT, SOD and GPx. Several authors suggest that moderate levels of toxic reactants can induce increase of AEs activities, while very high levels of reactants can induce their decrease, as a consequence of damage of the molecular machinery required to induce AEs. Based on a great amount of experiments, which were done and described within this paper, we can say that the above mentioned principle does not apply in general. Only the reactions of t-BHP affected HepG2 cells were consistent with this idea. PMID- 26278150 TI - Anti-tumor immunity elicited by cross-linking vaccine heat shock protein 72 and alpha-fetoprotein epitope peptide. AB - Hepatocellular carcinoma (HCC) is one of the most common malignancies over the world. Alpha-fetoprotein (AFP) is an oncofetal protein during HCC development, which could generate weaker and less reproducible antitumor protection, and may serve as a target for immunotherapy. Therefore, it is imperative to enhance its immunogenicity and develop therapeutic vaccines to eliminate AFP-expressing tumors. In this study, by using glutaraldehyde cross-linking, we constructed a potential therapeutic peptide vaccine, heat shock protein 72 (HSP72) and AFP epitope peptide (HSP72/AFP-P). ELISPOT was applied to evaluate the quantity of AFP-specific CD8+ T cell that secreted IFN-gamma in immunized BALB/C mice. Granzyme B released from natural killer cells and AFP-specific antibody responses in immunized mice were detected by ELISA. The anti-tumor effects were investigated by in vitro cytotoxic T-lymphocyte assays and in vivo tumor therapeutic experiments. The results showed that reconstructed HSP72 and AFP epitope peptide vaccine synergistically exhibited significant increases in AFP specific CD8+ T cells, natural killer cells responses and impressive antitumor effects against AFP-expressing tumors. Immunization of BALB/C mice with HSP72/AFP P vaccine elicited stronger T-cells responses. The numbers of IFN-gamma-producing CD8+ T cells from mice immunized with HSP72/AFP-P were 30 times more than those from mice immunized with AFP-P, HSP72 or PBS (P < 0.01). The concentration of granzyme B in natural killer cells from mice immunized with HSP72/AFP-P were 15 times higher than that from other groups (P < 0.01). In vitro effector cells from mice immunized with HSP72/AFP-P showed much stronger cytolytic effect on H22 target cells than those from mice vaccinated with AFP-P, HSP72 or PBS (P < 0.01). Priming mice with the reconstructed vaccine exhibited robust strong protective immunity. Mice immunized with HSP72 or AFP-P alone demonstrated higher average tumor volumes than mice immunized with HSP72/AFP-P (P < 0.05). Our study suggests that constructing a tumor vaccine by cross-linking AFP antigen epitope peptide and HSP72 is a promising approach for cancer therapy. PMID- 26278151 TI - MicroRNA-141 regulates the tumour suppressor DLC1 in colorectal cancer. AB - Our previous study has showed that DLC1 acts as a functional tumor suppressor in colorectal cancer (CRC) cell lines. The aims of this study were to determine whether DLC1 is a target of MicroRNA (miRNA) regulation and to evaluate the role of this mechanism in CRC. By bioinformatics approach and literature, miR-141 was chosen for further study. The miR-141 mimic, miR-141 inhibitor were synthesized and transfected to Lovo cells. Cell growth was determined by MTT and in vivo models. The flow cytometric analysis for cell cycle determination and transwell assays for evaluating the cell invasion were used. Luciferase reporter assays and Western blots showed that DLC1 was a direct target of miR-141 in CRC. The expression levels of miR-141 were obviously up-regulated in CRC tissues compared to non-cancerous tissues, while DLC1 expression levels were down-regulated in a high proportion of clinical samples (14/18). In addition, correlation analyses revealed negative correlation between miR-141 levels and DLC1 expression levels in CRC tissues. MiR-141 overexpression promoted cell growth in vitro and in vivo, promoted cell cycle progression and invasion in Lovo cells. Furthermore, re introduction of DLC-1 in miR-141-overexpressing Lovo cells decreased growth rate of cells, increase of the percentage in G0/G1 phase and decreased the number of migrating cells. In conclusion, we demonstrated that miR-141 is up-regulated in CRC and acts as a functional oncogene by targeting DLC1. PMID- 26278152 TI - Diagnostics and treatment of insulinoma. AB - Insulinomas are the most common functioning pancreatic neuroendocrine neoplasms (pNENs), developed mainly from pancreatic islet cells. More than 90% of insulinomas are sporadic, benign and small sized. Autonomous production of insulin results in neuroglycopenic and adrenergic symptomatology with potential lethality. Surgery remains the only curative treatment with a high success rate. Preoperative tumor localization is challenging, but important for appropriate surgical approach. Metastatic forms represent a challenge, mainly on the field of therapy, with the need of tumor burden reduction and glycemia stabilization. The rarity of malignant forms limits reports on therapeutic strategies and outcome. Authors present in this article a summarized overview of epidemiology, clinic, diagnostics and treatment of benign and malign forms of insulinomas. PMID- 26278153 TI - Biomarkers for determination prostate cancer: implication for diagnosis and prognosis. AB - Prostate cancer (PCa) belongs to most common cancers and it is the second leading cause of cancer death in men. A genetic predisposition or acquired genetic and epigenetic changes with effect of other factors, such as advanced age, race and environmental factors contribute to PCa development. PCa is a very heterogeneous disease that is characterized by different clinical behavior, from indolent, slow growing tumors to aggressive, fast-growing tumors with lethal progression. Early diagnostics and identification of PCa type are crucial prerequisites for efficient treatment of patients. Recently, the diagnostics of early stages of PCa is based mostly on evaluation of prostate-specific antigen (PSA) in serum of patients. Men with high levels of PSA undergo biopsy in order to determine histopatological grading of PCa - Gleason scoring which classifies tumors from most to least differentiated as well as staging - determination of the status of their primary tumors, with or without lymph node involvement. The results from this screening diagnosis lead into conventional treatment, including radical prostatectomy and brachytherapy. In case of advanced PCa, conventional treatment continues with androgen deprivation therapy. However, in many cases the cancer recurs. Therefore, the clinicians and researchers are forced to find more precise and sensitive biomarker suitable for PCa diagnostics as well as prognostics and therapy. This paper provides review of current most promising molecular and immunohistochemical biomarkers in PCa diagnosis, prognosis and clinical behavior. PMID- 26278154 TI - Pol zeta polymorphisms are associated with platinum based chemotherapy response and side effects among non-small cell lung cancer patients. AB - Lung cancer is the greatest contributor to tumor-derived death. Traditionally, platinum-based chemotherapies are the primary treatment for most patients. However, intrinsic drug resistance and side effects limit the efficacy of platinum-based chemotherapies. Previous studies demonstrated that Pol zeta can modulate cellular sensitivity to chemotherapy. The primary aim of this study was to investigate the potential role of the polymorphism of Pol zeta in platinum based chemotherapy tolerance and side effects. A total of 663 patients who were newly histologically diagnosed with advanced NSCLC were enrolled. Their treatment response was classified into four categories: complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). The gastrointestinal and hematological toxicity incidence was assessed twice a week during the entire first line of treatment. Thirteen SNPs of REV3 and REV7 were genotyped. The associations between SNPs and the treatment response or toxicity were analyzed with a logistic regression model. We discovered that five SNPs were correlated with the treatment response. Specifically, rs240969 was significantly associated with the treatment response, after a Bonferroni correction, in smokers and a combined cohort (P=0.048 and P=0.0082, respectively) as well as with rs3218573 in smokers (P=0.036). In addition, we discovered that the incidence of grade 3 or 4 gastrointestinal toxicity was significantly higher in patients carrying a G/G genotype of rs240966 or an A allele of rs456865. We also identified that five SNPs, namely rs240966, rs4945880, rs465646, rs2233025 and rs2336030, that were correlated with an increased risk of grade 3 or grade 4 hematologic toxicity. The REV3 and REV7 polymorphisms are in a catalytic subunit and an accessory subunit of Pol zeta, respectively, and participate in platinum chemotherapy tolerance and side effects. PMID- 26278155 TI - Immunoparesis in MGUS - Relationship of uninvolved immunoglobulin pair suppression and polyclonal immunoglobuline levels to MGUS risk categories. AB - Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic, potentially malignant condition. It has been established that annually approximately 1-2% of MGUS cases transforms into one of the malignant forms of monoclonal gammopathies. Progression risk factors include the quantity and type of M-protein, and namely the ratio of free light immunoglobulin chains (FLC). These factors, enable purposeful stratification of MGUS individuals. Some authors consider suppression of polyclonal immunoglobulin levels to be another progression factor. The aim of the study was to compare polyclonal immunoglobulin (PIg) levels with uninvolved heavy/light chain pair (HLC) levels in order to verify the degree of immunoparesis depending on MGUS risk category (0-3). The analyzed set consisted of 159 serum samples from MGUS patients (102 IgG, 57 IgA), who were stratified into 4 risk groups (0 - low, 1 - low-intermediate, 2 - high intermediate and 3 - high risk of transformation). The results of analysis showed that with increasing degree of MGUS increases risk of immune paresis defined by decreasing levels of polyclonal immunoglobulins, ie. IgA and IgM in the case of IgG MGUS, respectively, IgG and IgM in case of IgA MGUS. Significant differences were also found when analyzing the levels of uninvolved HLC pairs IgG kappa (resp. IgG lambda) in IgG lambda (IgG kappa) dominant secretion. In the case of MGUS with IgA isotype, the results were similar. Discovery of the connection between the degree of immunosuppression and the level of MGUS risk contributes to our understanding of the relationship between biology, development and potential malignant transformation of MGUS. It is apparent that uninvolved HLC pair assay enables more reliable identification of at-risk MGUS patients than a simple quantitative assay for polyclonal immunoglobulins alone. PMID- 26278156 TI - A 39-gene signature is associated with early occurrence of distant metastasis in primary lymph-node negative breast cancers. AB - Risk factors of the development of distant metastasis in primary node-negative breast cancer patients are heterogeneous. Identification of patients at high risk of early distant metastasis is of important clinical significance. In the current study, using the already published datasets, we develop a gene signature that can robustly predict early distant metastasis for patients with primary node-negative breast cancer. We identified a 39-gene signature, which were associated with distant metastasis and shorter distant metastasis free survival (DMFS) in node negative breast cancers. Using the survival prediction analysis method in BRB Array tools, this signature can stratify patients into early- and late- distant metastasis subgroups with different DMFS in VDX training dataset (AUC=0.734, P < 0.01). And we further validated the reliability of the prognostic value of this 39-gene signature in another two independent breast cancer cohorts (NKI dataset, AUC=0.642, P<0.0167; TRANSBIG dataset, AUC=0.711, P<0.0167). Furthermore, the early distant metastasis subgroups defined by the 39-gene signature exhibited a significant association with ER negative status and more aggressive molecular subtypes in all three datasets, and with poor differentiation status in two datasets. In summary, we developed a novel distant metastasis-related gene signature for predicting early occurrence of distant metastasis in node-negative breast cancers, what might be useful in making treatment decisions for these early metastasis patients. PMID- 26278157 TI - [Association of estrogens and selective estrogens receptors modulators: towards a renewal of the hormonal treatment?]. AB - The life expectancy of women has risen in the past century from 48years to more than 80. The decline of endogenous estrogen production (in particular, the principal circulating physiological hormone, 17beta-estradiol) at menopause (which occurs at an average of 51years) is often accompanied by a series of functional disorders that affect quality of life (QoL). This estrogen deficiency affects different tissues and results in an increase in the prevalence of various disorders, including but not limited to osteoporosis and cardiovascular disease. Hormone therapy for menopause is a relatively recent biomedical challenge, which underwent a downturn after the Women Health Initiative study of older postmenopausal women. We will summarize the WHI findings in the first part of this article. At Inserm unit 1048, we are working on understanding the protective effects of estrogen against the development of atherosclerosis and type 2 diabetes in murine models. We have also focused in recent years on modeling the impact of estrogen in thrombosis models, to attempt to clarify the complex relation between estrogen and thrombotic risk. In part II of this article, we will describe a new strategy of hormone therapy for menopause, combining estrogens and selective estrogen receptor modulators (SERM). We review the scientific underpinnings of this strategy, which may enable the renewal of hormone therapy for menopause. PMID- 26278158 TI - Identification and expression of lypc, a novel dark-inducible member of Ly6 superfamily in zebrafish Danio rerio. AB - Snake venom neurotoxins and lymphocyte antigen-6 (Ly6) family members identified in many metazoans possess conserved LU domain containing eight or ten conserved cysteine residues which form 4 to 5 conserved disulfide bonds. They are found to execute a wide variety of biological effects, but information regarding Ly6 superfamily in zebrafish remains rather limited. Here we identified a novel Ly6 gene located on the chromosome 15 in zebrafish, and named it lypc highlighting its predominant expression in the pigment cells. Both homology modeling and sequence comparison revealed that lypc has features typical of Ly6 family members. Whole mount in situ hybridization showed that lypc was expressed in the trunk pigment cells and retinal pigment cells. Moreover, real-time quantitative PCR demonstrated that the expression of lypc was subjected to diurnal variation regulation, i.e. the expression of lypc displays a clear rhythmic pattern, and dark exposure apparently stimulated its expression. Collectively, these data indicate that lypc is a novel dark-inducible Ly6 member with a predominant expression in the pigment cells of zebrafish, laying a foundation for further elucidation of its functions. PMID- 26278159 TI - MRS for non-invasive medulloblastoma subgrouping. PMID- 26278160 TI - Docetaxel for hormone-sensitive metastatic prostate cancer. PMID- 26278161 TI - Hypofractionated breast radiation reduces acute toxicities. PMID- 26278162 TI - Research funding under review in UK and USA. PMID- 26278163 TI - France establishes guidelines for treating neurobehavioral disorders following traumatic brain injury. AB - This paper comments on the report by a committee of La Societe Francaise de Medecine Physique et de Readaptation (SOFMER) in response to the Haute Autorite de sante in France concerning the classification and clinical management of disorders of comportment following moderate to severe traumatic brain injury (TBI). In view of the large number of patients and families affected by these disorders, there is a strong rationale for these guidelines to ensure that clinical assessment and treatment is evidence-based. The report is viewed from the perspective of current research on disorders of comportment and in relation to recent reviews and meta-analyses on this topic. Comments on the classification draw on pathophysiology and brain imaging in addition to the clinical literature. The SOFMER report and recent projects in North America are compared for trends in the development of recommended assessment scales and standard, evidence-based treatment protocols for pharmacologic and non-pharmacologic interventions. Collaborative, multinational investigations of TBI are also noted, which are advancing progress toward guidelines for clinical management. PMID- 26278164 TI - Dickkopf-3 (DKK-3) obstructs VEGFR-2/Akt/mTOR signaling cascade by interacting of beta2-microglobulin (beta2M) in ovarian tumorigenesis. AB - In this study, we investigated a possible mechanism of beta2-microglobulin (beta2M) function in cancer metastases in vitro, using a human ovarian carcinoma cell line. beta2M, a modulator acts as a cell growth-promoting and cellular signaling factors, was identified as a dickkopf-3 (DKK-3) interacting protein. We also observed that DKK-3 suppresses endothelial cell angiogenesis of beta2M through vascular endothelial growth factor receptor-2 (VEGFR-2) in tumorigenesis. Luciferase activity was remarkably reduced by the transfection of DKK-3 in a dose dependent manner. In addition, over-expression of beta2M activates cell growth by suppressing DKK-3-induced apoptosis. The effect of beta2M on cell cycle and apoptosis-regulatory components was also confirmed through the silencing of beta2M expression. Furthermore, induction of beta2M-mediated VEGFR-2/Akt/mTOR phosphorylation and tumor angiogenesis was significantly suppressed by over expression of DKK-3. Taken together, our results suggest an underlying mechanism for an increase of beta2M-related activity in ovarian tumor cells. PMID- 26278165 TI - The relative contributions of global and local acceleration components on speed perception and discriminability following adaptation. AB - The perception of speed is dependent on the history of previously presented speeds. Adaptation to a given speed regularly results in a reduction of perceived speed and an increase in speed discriminability and in certain circumstances can result in an increase in perceived speed. In order to determine the relative contributions of the local and global speed components on perceived speed, this experiment used expanding dot flow fields with accelerating (global), decelerating (global) and mixed accelerating/decelerating (local) speed patterns. Profound decreases in perceived speed are found when viewing low test speeds after adaptation to high speeds. Small increases in the perceived speed of high test speeds occur following adaptation to low speeds. There were small but significant differences in perceived stimulus speed after adaptation due to different acceleration profiles. No evidence for global modulation of speed discriminability following adaptation was found. PMID- 26278166 TI - Representation of higher-order statistical structures in natural scenes via spatial phase distributions. AB - Natural scenes contain richer perceptual information in their spatial phase structure than their amplitudes. Modeling phase structure of natural scenes may explain higher-order structure inherent to the natural scenes, which is neglected in most classical models of redundancy reduction. Only recently, a few models have represented images using a complex form of receptive fields (RFs) and analyze their complex responses in terms of amplitude and phase. However, these complex representation models often tacitly assume a uniform phase distribution without empirical support. The structure of spatial phase distributions of natural scenes in the form of relative contributions of paired responses of RFs in quadrature has not been explored statistically until now. Here, we investigate the spatial phase structure of natural scenes using complex forms of various Gabor-like RFs. To analyze distributions of the spatial phase responses, we constructed a mixture model that accounts for multi-modal circular distributions, and the EM algorithm for estimation of the model parameters. Based on the likelihood, we report presence of both uniform and structured bimodal phase distributions in natural scenes. The latter bimodal distributions were symmetric with two peaks separated by about 180 degrees . Thus, the redundancy in the natural scenes can be further removed by using the bimodal phase distributions obtained from these RFs in the complex representation models. These results predict that both phase invariant and phase sensitive complex cells are required to represent the regularities of natural scenes in visual systems. PMID- 26278167 TI - Detection of quercetin based on Al(3+)-amplified phosphorescence signals of manganese-doped ZnS quantum dots. AB - A simple phosphorescence method is proposed for quercetin detection based on Al(3+)-amplified room-temperature phosphorescence (RTP) signals of 3 mercaptopropionic acid (MPA)-capped Mn-doped ZnS quantum dots (QDs). The sensor was established based on some properties as follows. Al(3+) can interact with carboxyl groups on the surface of MPA-capped Mn-doped ZnS QDs via chelation, which will lead to the aggregation of QDs and amplification of RTP signals, After the addition of quercetin, it can form more stable complex with Al(3+) in alkaline aqueous solution and dissociate Al(3+) from the surface of Mn-doped ZnS QDs, which will result in significant recovery of RTP intensity of the MPA-capped Mn-doped ZnS-Al(3+) system. Under the optimized conditions, the change of RTP intensity was proportional to the concentration of quercetin in the range from 0.1 to 6.0 mg L(-1), with a high correlation coefficient of 0.996 and a detection limit of 0.047 mg L(-1). The proposed method is potentially suitable for detection of quercetin in real samples without complicated pretreatment. PMID- 26278168 TI - Synthesis and detection of N-sulfonated oversulfated chondroitin sulfate in marketplace heparin. AB - N-sulfonated oversulfated chondroitin sulfate (NS-OSCS), recently reported as a potential threat to the heparin supply, was prepared along with its intermediate derivatives. All compounds were spiked into marketplace heparin and subjected to United States Pharmacopeia (USP) identification assays for heparin (proton nuclear magnetic resonance [(1)H NMR], chromatographic identity, % galactosamine [%GalN], anti-factor IIa potency, and anti-factor Xa/IIa ratio). The U.S. Food and Drug Administration (FDA) strong-anionic exchange high-performance liquid chromatography (SAX-HPLC) method resolved NS-OSCS from heparin and OSCS and had a limit of detection of 0.26% (w/w) NS-OSCS. The %GalN test was sensitive to the presence of NS-OSCS in heparin. Therefore, current USP heparin monograph tests (i.e., SAX-HPLC and %GalN) detect the presence of NS-OSCS in heparin. PMID- 26278169 TI - Interfacial electron transfer of glucose oxidase on poly(glutamic acid)-modified glassy carbon electrode and glucose sensing. AB - The interfacial electron transfer of glucose oxidase (GOx) on a poly(glutamic acid)-modified glassy carbon electrode (PGA/GCE) was investigated. The redox peaks measured for GOx and flavin adenine dinucleotide (FAD) are similar, and the anodic peak of GOx does not increase in the presence of glucose in a mediator free solution. These indicate that the electroactivity of GOx is not the direct electron transfer (DET) between GOx and PGA/GCE and that the observed electroactivity of GOx is ascribed to free FAD that is released from GOx. However, efficient electron transfer occurred if an appropriate mediator was placed in solution, suggesting that GOx is active. The PGA/GCE-based biosensor showed wide linear response in the range of 0.5-5.5 mM with a low detection limit of 0.12 mM and high sensitivity and selectivity for measuring glucose. PMID- 26278170 TI - Use of cloud-point preconcentration for spectrophotometric determination of trace amounts of antimony in biological and environmental samples. AB - This work presents a cloud-point extraction process using the micelle-mediated extraction method for simultaneous preconcentration and determination of Sb(III) and Sb(V) species in biological and environmental samples as a prior preconcentration step to their spectrophotometric determination. The analytical system is based on the selective reaction between Sb(III) and 3-dichloro-6-(3 carboxy-2-hydroxy-1-naphthylazo)quinoxaline (DCHNAQ) in the presence of cetyltrimethylammonium bromide (CTAB) and potassium iodide at pH 4.5. Total Sb concentration was determined after reduction of Sb(V) to Sb(III) in the presence of potassium iodide and ascorbic acid. The optimal reaction conditions and extraction were studied, and the analytical characteristics of the method (e.g., limits of detection and quantification, linear range, preconcentration, improvement factors) were obtained. Linearity for Sb(III) was obeyed in the range of 0.2-20 ng ml(-1). The detection and quantification limits for the determination of Sb(III) were 0.055 and 0.185 ng ml(-1), respectively. The method has a lower detection limit and wider linear range, inexpensive instrument, and low cost, and is more sensitive compared with most other methods. The interference effect of some anions and cations was also studied. The method was applied to the determination of Sb(III) in the presence of Sb(V) and total antimony in blood plasma, urine, biological, and water samples. PMID- 26278171 TI - A luminescent assay for real-time measurements of receptor endocytosis in living cells. AB - Ligand-mediated endocytosis is a key autoregulatory mechanism governing the duration and intensity of signals emanating from cell surface receptors. Due to the mechanistic complexity of endocytosis and its emerging relevance in disease, simple methods capable of tracking this dynamic process in cells have become increasingly desirable. We have developed a bioluminescent reporter technology for real-time analysis of ligand-mediated receptor endocytosis using genetic fusions of NanoLuc luciferase with various G-protein-coupled receptors (GPCRs). This method is compatible with standard microplate formats, which should decrease work flows for high-throughput screens. This article also describes the application of this technology to endocytosis of epidermal growth factor receptor (EGFR), demonstrating potential applicability of the method beyond GPCRs. PMID- 26278172 TI - Improvement of heme oxygenase-1-based heme sensor for quantifying free heme in biological samples. AB - We recently reported a novel heme sensor using fluorescently labeled heme oxygenase-1; however, its inherent enzyme activity would be a potential obstacle in quantifying heme in biological samples. Here, we found that mutation of the catalytically important residue, Asp140, with histidine in the sensor not only diminished the heme degradation activity but also increased heme binding affinity. The sensor with a visible fluorophore was also found to be beneficial to avoid background emission from endogenous substance in biological samples. By using the improved heme sensor, we succeeded in quantifying free heme in rat hepatic samples for the first time. PMID- 26278174 TI - An Isoform-Specific Myristylation Switch Targets Type II PKA Holoenzymes to Membranes. AB - Cyclic AMP-dependent protein kinase (PKA) is regulated in part by N-terminal myristylation of its catalytic (C) subunit. Structural information about the role of myristylation in membrane targeting of PKA has been limited. In mammalian cells there are four functionally non-redundant PKA regulatory subunits (RIalpha, RIbeta, RIIalpha, and RIIbeta). PKA is assembled as an inactive R2C2 holoenzyme in cells. To explore the role of N-myristylation in membrane targeting of PKA holoenzymes, we solved crystal structures of RIalpha:myrC and RIIbeta2:myrC2, and showed that the N-terminal myristylation site in the myrC serves as a flexible "switch" that can potentially be mobilized for membrane anchoring of RII, but not RI, holoenzymes. Furthermore, we synthesized nanodiscs and showed by electron microscopy that membrane targeting through the myristic acid is specific for the RII holoenzyme. This membrane-anchoring myristylation switch is independent of A Kinase Anchoring Proteins (AKAPs) that target PKA to membranes by other mechanisms. PMID- 26278173 TI - Novel Inter-Subunit Contacts in Barley Stripe Mosaic Virus Revealed by Cryo Electron Microscopy. AB - Barley stripe mosaic virus (BSMV, genus Hordeivirus) is a rod-shaped single stranded RNA virus similar to viruses of the structurally characterized and well studied genus Tobamovirus. Here we report the first high-resolution structure of BSMV at 4.1 A obtained by cryo-electron microscopy. We discovered that BSMV forms two types of virion that differ in the number of coat protein (CP) subunits per turn and interactions between the CP subunits. While BSMV and tobacco mosaic virus CP subunits have a similar fold and interact with RNA using conserved residues, the axial contacts between the CP of these two viral groups are considerably different. BSMV CP subunits lack substantial axial contacts and are held together by a previously unobserved lateral contact formed at the virion surface via an interacting loop, which protrudes from the CP hydrophobic core to the adjacent CP subunit. These data provide an insight into diversity in structural organization of helical viruses. PMID- 26278175 TI - A Suite of Engineered GFP Molecules for Oligomeric Scaffolding. AB - Applications ranging from synthetic biology to protein crystallization could be advanced by facile systems for connecting multiple proteins together in predefined spatial relationships. One approach to this goal is to engineer many distinct assembly forms of a single carrier protein or scaffold, to which other proteins of interest can then be readily attached. In this work we chose GFP as a scaffold and engineered many alternative oligomeric forms, driven by either specific disulfide bond formation or metal ion addition. We generated a wide range of spatial arrangements of GFP subunits from 11 different oligomeric variants, and determined their X-ray structures in a total of 33 distinct crystal forms. Some of the oligomeric GFP variants show geometric polymorphism depending on conditions, while others show considerable geometric rigidity. Potential future applications of this system are discussed. PMID- 26278176 TI - GraDeR: Membrane Protein Complex Preparation for Single-Particle Cryo-EM. AB - We developed a method, named GraDeR, which substantially improves the preparation of membrane protein complexes for structure determination by single-particle cryo electron microscopy (cryo-EM). In GraDeR, glycerol gradient centrifugation is used for the mild removal of free detergent monomers and micelles from lauryl maltose-neopentyl glycol detergent stabilized membrane complexes, resulting in monodisperse and stable complexes to which standard processes for water-soluble complexes can be applied. We demonstrate the applicability of the method on three different membrane complexes, including the mammalian FoF1 ATP synthase. For this highly dynamic and fragile rotary motor, we show that GraDeR allows visualizing the asymmetry of the F1 domain, which matches the ground state structure of the isolated domain. Therefore, the present cryo-EM structure of FoF1 ATP synthase provides direct structural evidence for Boyer's binding change mechanism in the context of the intact enzyme. PMID- 26278177 TI - Structural Insight into the Mechanism of TFIIH Recognition by the Acidic String of the Nucleotide Excision Repair Factor XPC. AB - In global genome repair (GGR), XPC detects damaged nucleotides and recruits TFIIH complex. The small acidic region of XPC binds to the pleckstrin homology (PH) domain of TFIIH subunit p62; however, the recognition mechanism remains elusive. Here, we use nuclear magnetic resonance to present the tertiary structure of XPC bound to the PH domain. The XPC acidic region forms a long string stabilized by insertion of Trp133 and Val136 into two separate hollows of the PH domain, coupled with extensive electrostatic contacts. Analysis of several XPC mutants revealed that particularly Trp133 is essential for binding to the PH domain. In cell lines stably expressing mutant XPC, alanine substitution at Trp133 or Trp133/Val136 compromised UV resistance, recruitment of TFIIH to DNA damage, and removal of UV-induced photoproducts from genomic DNA. These findings show how TFIIH complex is recruited by XPC to damaged DNA, advancing our understanding of the early stage of GGR. PMID- 26278178 TI - Laser-guided magic bullets-A non-antibiotic answer to O'Neill. PMID- 26278179 TI - Transcriptome and proteome of the highly neurotoxic venom of Gloydius intermedius. AB - The venomics of Gloydius intermedius were investigated using expressed sequence tags (ESTs) analyses, 2D gel-electrophoresis combined with MALDI-TOF/TOF, and LC MS/MS. A total of 1920 ESTs from the venom gland cDNA library were sequenced; 74% of them belonged to toxin-families. The four most abundant families among the toxin transcripts were: serine protease (SP, 36.2%), bradykinin potentiating peptide (25.3%), l-amino acid oxidase (LAAO, 13.1%), and phospholipase A2 (PLA2, 9.9%). Moreover, the full sequences of four PLA2s, eight SPs, cysteine-rich secretory protein (CRISP), C-type-lectin-like-protein (CTLP), hyaluronidase, metalloproteinase, and nerve growth factor were deduced from the cDNA sequences. Excluding the CRISP and hyaluronidase, most of the G. intermedius venom proteins bear 92-99% sequence identities to those of other pitviper venoms. The most abundant components are PLA2s (37%), SPs (20%) and LAAO (6%), while metalloproteinase, CTLP, and other components each account for <3% of the total venom proteins. The abundance of Gintexin (a crotoxin-like neurotoxin) and low levels of hemorrhagic metalloproteases, disintegrins and CTLPs highlight the great venom differences between G. intermedius and other hemorrhagic pitvipers. The bimorphism of hemorrhagic and neurotoxic venoms among Gloydius is confirmed; our results shed more lights on the co-evolution of both neurotoxicity and hypotension in some viperid venoms. PMID- 26278181 TI - In vitro wear testing of a contemporary design of reverse shoulder prosthesis. AB - Reverse shoulder arthroplasty is an increasingly common surgical intervention. However there are concerns and known limitations in relation to such joint replacement, while novel designs of reverse shoulder prostheses continue to appear on the market. Many claim to offer improvements over older designs but such assertions are difficult to validate when there is no consensus as to how such implants should be tested in vitro or even if such testing is necessary. In order to permit appropriate in vitro testing of reverse shoulder prostheses a unique, multi-station test rig was designed which was capable of applying motion in three axes to test prostheses. The shoulder simulator can apply up to 110 degrees of motion in the flexion-extension and abduction-adduction axes and up to 90 degrees in the internal-external rotation axis. Dynamic loading of up to 1500 N can be provided. The simulator is computer controlled so that the motions and loading associated with particular activities of daily living can be applied. A 4.5 million cycle wear test of commercially available reverse shoulder prostheses was undertaken using a 'mug to mouth' activity of daily living. Gravimetric analysis was used to characterise wear. After 4.5 million cycles of 'mug to mouth', the average wear rate of the test components was 14.3mm(3)/million cycles. Polyethylene test components showed a reduction in roughness and the median wear particle diameter was 167 nm. A three axis shoulder simulator has been designed and used to successfully test multiple samples of a commercially available reverse shoulder prosthesis. PMID- 26278182 TI - Intracellular and extracellular O-linked N-acetylglucosamine in the nervous system. AB - Addition of O-linked N-acetylglucosamine (O-GlcNAc) to the hydroxyl group of serine and threonine residues (O-GlcNAcylation) is a post-translational modification common to multicellular eukaryotes. To date, O-GlcNAcylations have been divided into two categories: the first involves nucleocytoplasmic and mitochondrial (intracellular) O-GlcNAcylation catalyzed by O-GlcNAc transferase (OGT), and the second involves O-GlcNAcylation in the secretory pathways (extracellular) catalyzed by epidermal growth factor (EGF) domain-specific O GlcNAc transferase (EOGT). Intracellular O-GlcNAcylation is involved in essential cellular and physiological processes such as synaptic activity, neuronal morphogenesis, and learning and memory. Moreover, intracellular O-GlcNAc might have a neuroprotective effect, protecting against neurodegenerative diseases such as Alzheimer's disease. EGF repeats on extracellular matrix proteins and the extracellular region of transmembrane proteins have recently been found to be modified by O-GlcNAc in the mouse cerebral cortex. EOGT is responsible for Adams Oliver syndrome, a rare congenital disorder characterized by aplasia cutis congenita and terminal transverse limb defects, often accompanied by cardiovascular and neurological defects. Thus, a mechanistic understanding of O GlcNAc in the regulation of its target proteins is of importance from both a basic science and a clinical-translational perspective. In this review, we summarize the current understanding of the physiological and pathological significances of both types of O-GlcNAcylations found in the nervous system. PMID- 26278180 TI - Structural Modeling of GR Interactions with the SWI/SNF Chromatin Remodeling Complex and C/EBP. AB - The glucocorticoid receptor (GR) is a steroid-hormone-activated transcription factor that modulates gene expression. Transcriptional regulation by the GR requires dynamic receptor binding to specific target sites located across the genome. This binding remodels the chromatin structure to allow interaction with other transcription factors. Thus, chromatin remodeling is an essential component of GR-mediated transcriptional regulation, and understanding the interactions between these molecules at the structural level provides insights into the mechanisms of how GR and chromatin remodeling cooperate to regulate gene expression. This study suggests models for the assembly of the SWI/SNF-A (SWItch/Sucrose-NonFermentable) complex and its interaction with the GR. We used the PRISM algorithm (PRotein Interactions by Structural Matching) to predict the three-dimensional complex structures of the target proteins. The structural models indicate that BAF57 and/or BAF250 mediate the interaction between the GR and the SWI/SNF-A complex, corroborating experimental data. They further suggest that a BAF60a/BAF155 and/or BAF60a/BAF170 interaction is critical for association between the core and variant subunits. Further, we model the interaction between GR and CCAAT-enhancer-binding proteins (C/EBPs), since the GR can regulate gene expression indirectly by interacting with other transcription factors like C/EBPs. We observe that GR can bind to bZip domains of the C/EBPalpha homodimer as both a monomer and dimer of the DNA-binding domain. In silico mutagenesis of the predicted interface residues confirm the importance of these residues in binding. In vivo analysis of the computationally suggested mutations reveals that double mutations of the leucine residues (L317D+L335D) may disrupt the interaction between GR and C/EBPalpha. Determination of the complex structures of the GR is of fundamental relevance to understanding its interactions and functions, since the function of a protein or a complex is dictated by its structure. In addition, it may help us estimate the effects of mutations on GR interactions and signaling. PMID- 26278183 TI - The Prototypic Cyclotide Kalata B1 Has a Unique Mechanism of Entering Cells. AB - Cyclotides combine the stability of disulfide-rich peptides with the intracellular accessibility of cell-penetrating peptides, giving them outstanding potential as drug scaffolds with an ability to inhibit intracellular protein protein interactions. To realize and optimize the application of cyclotides as a drug framework and delivery system, we studied the ability of the prototypic cyclotide, kalata B1, to enter mammalian cells. We show that kalata B1 can enter cells via both endocytosis and direct membrane translocation. Both pathways are initiated by targeting phosphatidylethanolamine phospholipids at the cell surface and inducing membrane curvature. This unusual approach to initiate internalization might be harnessed to deliver drugs into cells and, in particular, cancer cells, which present a higher proportion of surface-exposed phosphatidylethanolamine phospholipids. Our findings highlight the potential of these peptides as drug leads for the modulation of traditionally "undruggable" targets, such as intracellular protein-protein interactions. PMID- 26278184 TI - The Structure and Interactions of Periplasmic Domains of Crucial MmpL Membrane Proteins from Mycobacterium tuberculosis. AB - Mycobacterium tuberculosis mycobacterial membrane protein large (MmpL) proteins are important in substrate transport across the inner membrane. Here, we show that MmpL proteins are classified into two phylogenetic clusters, where MmpL cluster II contains three soluble domains (D1, D2, and D3) and has two full length members, MmpL3 and MmpL11. Significantly, MmpL3 is currently the most druggable M. tuberculosis target. We have solved the 2.4-A MmpL11-D2 crystal structure, revealing structural homology to periplasmic porter subdomains of RND (multidrug) transporters. The resulting predicted cluster II MmpL membrane topology has D1 and D2 residing, and possibly interacting, within the periplasm. Crosslinking and biolayer interferometry experiments confirm that cluster II D1 and D2 bind with weak affinities, and guided D1-D2 heterodimeric model assemblies. The predicted full-length MmpL3 and MmpL11 structural models reveal key substrate binding and transport residues, and may serve as templates to set the stage for in silico anti-tuberculosis drug development. PMID- 26278185 TI - A General Method for Insertion of Functional Proteins within Proteins via Combinatorial Selection of Permissive Junctions. AB - A major goal of modern protein chemistry is to create new proteins with different functions. One approach is to amalgamate secondary and tertiary structures from different proteins. This is difficult for several reasons, not the least of which is the fact that the junctions between secondary and tertiary structures are not degenerate and usually affect the function and folding of the entire complex. Here, we offer a solution to this problem by coupling a large combinatorial library of about 10(7) different N- and C-terminal junctions to a powerful system that selects for function. Using this approach, the entire Leptin and follicle stimulating hormone (FSH) were inserted into an antibody. Complexes with full retention of function in vivo and in vitro, although rare, were found easily by using an autocrine selection system to search for hormonal activity. Such large diversity systems, when coupled to robust selection systems, should enable construction of novel therapeutic proteins. PMID- 26278186 TI - Deaths from acute abdominal conditions and geographical access to surgical care in India: a nationally representative spatial analysis. AB - BACKGROUND: Few population-based studies quantify mortality from surgical conditions and relate mortality to access to surgical care in low-income and middle-income countries. METHODS: We linked deaths from acute abdominal conditions within a nationally representative, population-based mortality survey of 1.1 million households in India to nationally representative facility data. We calculated total and age-standardised death rates for acute abdominal conditions. Using 4064 postal codes, we undertook a spatial clustering analysis to compare geographical access to well-resourced government district hospitals (24 h surgical and anaesthesia services, blood bank, critical care beds, basic laboratory, and radiology) in high-mortality or low-mortality clusters from acute abdominal conditions. FINDINGS: 923 (1.1%) of 86,806 study deaths at ages 0-69 years were identified as deaths from acute abdominal conditions, corresponding to 72,000 deaths nationally in 2010 in India. Most deaths occurred at home (71%) and in rural areas (87%). Compared with 567 low-mortality geographical clusters, the 393 high-mortality clusters had a nine times higher age-standardised acute abdominal mortality rate and significantly greater distance to a well-resourced hospital. The odds ratio (OR) of being a high-mortality cluster was 4.4 (99% CI 3.2-6.0) for living 50 km or more from well-resourced district hospitals (rising to an OR of 16.1 [95% CI 7.9-32.8] for >100 km). No such relation was seen for deaths from non-acute surgical conditions (ie, oral, breast, and uterine cancer). INTERPRETATION: Improvements in human and physical resources at existing government hospitals are needed to reduce deaths from acute abdominal conditions in India. Full access to well-resourced hospitals within 50 km by all of India's population could have avoided about 50,000 deaths from acute abdominal conditions, and probably more from other emergency surgical conditions. FUNDING: Bill & Melinda Gates Foundation, Dalla Lana School of Public Health, Canadian Institute of Health Research. PMID- 26278187 TI - A hospital too far--access to surgical facilities in India. PMID- 26278188 TI - Fluoride and nitrate removal from brackish groundwaters by batch-mode capacitive deionization. AB - Capacitive deionization (CDI) is an emerging water desalination technology in which pairs of porous electrodes are electrically charged to remove ionic species from water. In this work, the feasibility of fluoride and nitrate removal from brackish groundwaters by batch-mode CDI was investigated. Initially, the effects of flow rate, initial fluoride concentration, and initial coexisting NaCl concentration on fluoride removal were studied. The steady-state fluoride concentration declined as the initial fluoride concentration decreased while initial NaCl concentration remained constant. Due to the competitive electrosorption between fluoride and chloride for limited pore surface sites, a higher initial chloride concentration resulted in a higher equilibrium dissolved fluoride concentration. A simplified one-dimensional transport model for dual anions was developed and found to reliably describe the dynamic process of removal of both fluoride and chloride ions in CDI cells over a range of well defined operating conditions. Based on the ability of the model to describe fluoride removal, it was extended to description of nitrate removal from brackish groundwaters and also found to perform well. Thus, the approach to description of ion removal, at least in batch studies, appears robust and should assist in optimization of design and operating conditions such that optimal removal of trace ionic species is achieved even when high background concentrations of salt are present. PMID- 26278189 TI - A valid option for asthma control: Clinical evidence on efficacy and safety of fluticasone propionate/formoterol combination in a single inhaler. AB - A good level of asthma control improves the quality of life of asthmatic patients and may prevent future risk in term of exacerbations and decline of pulmonary function. However, in a real-life setting, several factors contribute to generally low compliance to the treatment. A rapid-onset, long-lasting medication with few adverse effects may contribute to improve adherence to therapy, along with an effective patient education and a good physician-patient communication. Many clinical studies demonstrated the comparable efficacy of the new fluticasone propionate/formoterol (FP/F) combination in a single inhaler to other combinations of inhaled corticosteroids and beta2agonists and the superiority of FP/F as compared to its individual components. Also the safety profile of this combination was encouraging in all studies, even at higher doses. By effectively and safely targeting both airway inflammation and smooth muscle dysfunction, the two pathological facets of asthma, and allowing the patient to adapt dose strength, FP/F combination in a single device represents a valid option to improve asthma control in patients with different levels of asthma severity. PMID- 26278190 TI - Roflumilast for asthma: Weighing the evidence. PMID- 26278191 TI - Nitrogen removal performance and microbial distribution in pilot- and full-scale integrated fixed-biofilm activated sludge reactors based on nitritation-anammox process. AB - Nitritation-anammox process was successfully established in pilot- and full-scale integrated fixed-film activated sludge (IFAS) reactors. An average nitrogen removal efficiency of 80% was achieved under ammonium loading rate of 0.7 1.3kgN/(m(3)d) in the pilot-scale reactor (12m(3)). Moreover, molecular analysis showed that ammonium oxidizing bacteria (AOB) were more abundant in the activated sludge while anammox bacteria were primarily located in the biofilm. The segregation of AOB and anammox bacteria enhanced the nitrogen removal rate and operational stability. Furthermore, a full-scale IFAS reactor of 500m(3) was set up to treat sludge dewatering liquors. An average nitrogen removal efficiency of 85% and a nitrogen removal rate of 0.48kgN/(m(3)d) were achieved after inoculation. It was noted that high influent suspended solids would seriously affect the performance of the IFAS system. Therefore, a pre-treatment was proposed to reduce suspended solid in the full-scale application. PMID- 26278192 TI - Non-Fullerene-Acceptor-Based Bulk-Heterojunction Organic Solar Cells with Efficiency over 7. AB - A novel perylene bisimide (PBI) dimer-based acceptor material, SdiPBI-S, was developed. Conventional bulk-heterojunction (BHJ) solar cells based on SdiPBI-S and the wide-band-gap polymer PDBT-T1 show a high power conversion efficiency (PCE) of 7.16% with a high open-circuit voltage of 0.90 V, a high short-circuit current density of 11.98 mA/cm(2), and an impressive fill factor of 66.1%. Favorable phase separation and balanced carrier mobilites in the BHJ films account for the high photovoltaic performance. The results demonstrate that fine tuning of PBI-based materials is a promising way to improve the PCEs of non fullerene BHJ organic solar cells. PMID- 26278193 TI - Studies on ascaridid, oxyurid and enoplid nematodes (Nematoda) from fishes of the Okavango River, Botswana. AB - Based on light and scanning electron microscopical studies, eight species (five adult and three larval) of nematodes belonging to the Ascaridida, Oxyurida and Enoplida were collected from fishes of the Okavango River, Botswana, namely Falcaustra similis Moravec et Van As, 2004, Atractidae gen. sp. (only female) (both Cosmocercoidea), Cucullanus sp. (only female) (Seuratoidea), Cithariniella longicaudata sp. n., Synodontisia annulata sp. n. (both Oxyuroidea), Contracaecum sp. third-stage larvae, third-stage larvae of Galeiceps sp. (both Ascaridoidea) and Eustrongylides sp. fourth-stage larvae (Dioctophymatoidea). The new species Citharinella longicaudata (type host Schilbe intermedius Ruppel) is mainly characterised by the shape and size of cephalic papillae and the spicule 108 um long, and Synodontisia annulata (type host S. intermedius) by the shape of cephalic papillae, body length of gravid females (4.88-5.33 mm) and a short spicule (66 um long). The female specimen of Cucullanus sp. from Tilapia sparmanni Smith markedly differs from congeners parasitising inland fishes in Africa by the elongate pseudobuccal capsule and by the excretory pore far posterior to the oesophago-intestinal junction; apparently, it belongs to an undescribed species. Galeiceps larvae parasitising fishes are described for the first time. Cithariniella gonzalezi Van Waerebeke, Chabaud, Bain et Georges, 1988 is considered a junior synonym of C. khalili Petter, Vassiliades et Troncy, 1972, and the previous records of Cithariniella citharini Khalil, 1964 from Synodontis spp. in Egypt concern, in fact, Cithariniella khalili Petter, Vassiliades et Troncy, 1972. The specimens of Cithariniella reported by Koubkova et al. (2010) from Paradistichodus dimidiatus (Pellegrin) in Senegal and misidentified as C. gonzalesi Van Waerebeke, Chabaud, Bain et Georges, 1988 are considered to represent a new species, C. koubkovae sp. n.; this is established by reference to the description and drawings provided by Koubkova et al. (2010). PMID- 26278194 TI - Laparoscopic sleeve gastrectomy: The rightful gold standard weight loss surgery procedure. PMID- 26278195 TI - Petersen's internal hernia complicating a laparoscopic omega loop gastric bypass. PMID- 26278197 TI - Complete genome sequence of Mycobacterium goodii X7B, a facultative thermophilic biodesulfurizing bacterium with industrial potential. AB - Mycobacterium goodii X7B appeared to have the ability to remove organic sulfur from a broad range of sulfur species in gasoline, diesel and crude oils. The predominant properties make it as a potential workhorse for petroleum biodesulfurization process. We sequenced and annotated the whole genome to serve as a basis for further elucidation of the genetic background of this promising strain, and provide opportunities for investigating the metabolic and regulatory mechanisms. PMID- 26278196 TI - Posttraumatic stress disorder symptoms and risky behaviors among trauma-exposed inpatients with substance dependence: The influence of negative and positive urgency. AB - BACKGROUND: Posttraumatic stress disorder (PTSD) among inpatients with substance use disorders (SUDs) is associated with heightened engagement in a variety of risky, self-destructive, and health-compromising behaviors (e.g., risky sexual behavior, aggression). Extant research provides support for the role of emotion dysregulation in the PTSD-risky behavior relation among inpatients with SUD; however, this research has been limited by a focus on emotion dysregulation involving negative (versus positive) emotions. The goal of the current study was to extend past research on the PTSD-risky behavior relation by examining the potential mediating roles of negative and positive urgency (two domains of emotion dysregulation defined by the tendency to engage in risky behavior in the context of negative and positive emotions, respectively). METHODS: Participants were 158 trauma-exposed inpatients with (n=91) and without (n=67) lifetime PTSD consecutively admitted to a residential SUD treatment facility (M age=34.34; 59.5% White, 50.6% female). Patients were administered diagnostic interviews and completed self-report questionnaires. RESULTS: Significant positive associations were found among lifetime PTSD symptoms, negative and positive urgency, and risky behaviors. Moreover, findings revealed significant indirect effects of lifetime PTSD symptoms on risky behaviors through the pathways of both negative and positive urgency. CONCLUSIONS: Results provide initial support for the mediating roles of both negative and positive urgency in the PTSD-risky behavior relation, highlighting the potential utility of teaching trauma-exposed inpatients with PTSD-SUD skills for tolerating negative and positive emotional states without engaging in maladaptive behaviors. PMID- 26278199 TI - Coordination structure and charge transfer in microsolvated transition metal hydroxide clusters [MOH](+)(H2O)1-4. AB - Infrared vibrational predissociation spectra of transition metal hydroxide clusters, [MOH](+)(H2O)1-4.D2 with M = Mn, Fe, Co, Ni, Cu, and Zn, are presented and analyzed with the aid of density functional theory calculations. For the [MnOH](+), [FeOH](+), [CoOH](+) and [ZnOH](+) species, we find that the first coordination shell contains three water molecules and the four ligands are arranged in a distorted tetrahedral geometry. [CuOH](+) can have either two or three water molecules in the first shell arranged in a planar arrangement, while [NiOH](+) has an octahedral ligand geometry with the first shell likely closed with five water molecules. Upon closure of the first coordination shell, characteristic stretch frequencies of hydrogen-bonded OH in the 2500-3500 cm(-1) region are used to pinpoint the location of the water molecule in the second shell. The relative energetics of different binding sites are found to be metal dependent, dictated by the first-shell coordination geometry and the charge transfer between the hydroxide and the metal center. Finally, the frequency of the hydroxide stretch is found to be sensitive to the vibrational Stark shift induced by the charged metal center, as observed previously for the smaller [MOH](+)(H2O) species. Increasing solvation modulates this frequency by reducing the extent of the charge transfer while elongating the M-OH bond. PMID- 26278198 TI - Influence of total genomic alteration and chromosomal fragmentation on response to a combination of azacitidine and lenalidomide in a cohort of patients with very high risk MDS. AB - We genetically analyzed a group of high risk MDS/AML patients treated by a combination of azacitidine and lenalidomide. In our cohort, the extent of genetic rearrangements was associated with outcome and response to treatment. The size of total genomic aberrations as defined by molecular karyotyping (SNP-array analysis) was a predictive marker for overall survival. TP53 mutations were associated with therapy refractoriness only if accompanied by heavily rearranged chromosomes. This study suggests a potential value of molecular karyotyping as a method to objectivate comprehensively the extent of genetic alterations in high risk patients with complex karyotypes, especially if the clinical value of the size of total genomic aberrations and the fragmentation status of single chromosomes could be evaluated in larger therapy trials. PMID- 26278200 TI - P-chiral 1-phosphanorbornenes: from asymmetric phospha-Diels-Alder reactions towards ligand design and functionalisation. AB - The principle of stereotopic face differentiation was successfully applied to 2H phospholes which undergo a very efficient and highly stereoselective Diels-Alder reaction giving phosphorus-chiral 1-phosphanorbornenes with up to 87% yield. The observed reaction pathway has been supported by theoretical calculations showing that the cycloaddition reaction between 2H-phosphole 3a and the dienophile (5R)-( )-menthyloxy-2(5H)-furanone (8) is of normal electron demand. Optically pure phosphanes were obtained by separation of the single diastereomers and subsequent desulfurisation of the sulfur-protected phosphorus atom. Finally, divergent ligand synthesis is feasible by reduction of the chiral auxiliary, subsequent stereospecific intramolecular Michael addition, and various functionalisations of the obtained key compound 13a. Furthermore, the unique structural properties of phospanorbornenes are presented and compared to those of phosphanorbornanes. PMID- 26278201 TI - Lamellar changes in the keratoconic cornea. AB - PURPOSE: The purpose of this study was to identify ultrastructural changes associated with ectasia and to determine the association between lamellar count and corneal thinning. METHODS: Five surgically removed keratoconic corneal buttons and four, non-keratoconic, normal eye bank control corneas were processed for transmission electron microscopy using an established protocol, ensuring minimal tissue distortion. A sequence of overlapping digital images, spanning the full apical cone corneal thickness, was assembled. A seamless digital montage was printed at 5000* magnification. Lamellae were counted in the anterior-posterior orientation, along a linear line, using established criteria for identification of individual lamellae. RESULTS: The stromal thickness estimated as a 95% confidence interval for the mean, CI (0.95), in the keratoconic corneas was 372 +/- 62 MUm, while in the normal cornea, it was 446 +/- 89 MUm. All keratoconic corneas showed ultrastructural evidence of lamellar splitting and a loss of interweaving anterior lamellae. In the keratoconic corneas, the median total linear stromal lamellar absolute count tangential to the corneal surface was 362, (25th percentile; 75th percentile) = (355; 365) lamellae and in the normal cornea, 246, (25th percentile; 75th percentile) = (239; 251). The linear lamellar density in the keratoconic corneas was estimated as CI (0.95) 117 +/- 22 and 86 +/-19 lamellae per 100 MUm in the anterior and posterior portion of the stroma, respectively. In normal cornea, the linear lamellar density was estimated as CI (0.95) 51 +/- 8 and 80 +/- 20 lamellae per 100 MUm. The mean difference of linear lamellar count between the anterior and the posterior portion of the cornea was estimated as CI (0.95) 31 +/- 23 for keratoconic corneas and -29 +/- 28 for the normal corneas. CONCLUSIONS: The current morphometric analysis of ultrastructural changes suggests that ectasia and thinning in keratoconus is associated with lamellar splitting into multiple bundles of collagen fibrils and loss of anterior lamellae. These structural changes, possibly in addition to lateral shifting of lamellae due to the pressure gradient over the cornea, are a potential explanation to the central loss of mass. PMID- 26278202 TI - Identification of a point mutation in the ace1 gene of Therioaphis trifolli maculata and detection of insecticide resistance by a diagnostic PCR-RFLP assay. AB - Aphids are important agricultural pests worldwide. Their control is largely based on chemical insecticides. One species that shows important invasive abilities and host-plant-related differences is Therioaphis trifolii (Monell) (Hemiptera: Aphididae). T. trifolii maculata, also known as spotted alfalfa aphid (SAA), can be very injurious to alfalfa crops in certain regions, such as in Saudi Arabia for effective control it is essential to diagnose and monitor the resistance mechanisms in the SAA populations. In the present study, we analysed acetylcholinesterase (ace) target site insensitivity mechanisms. A 650 bp length DNA containing the putative acetylcholinesterase (ace1) precursor was obtained and compared with other Hemipteran species. The sequences of many individual aphids collected from alfalfa crops in Saudi Arabia were analysed for the presence of resistance mutations: no resistance mutations were found at the resistance mutation loci 302; however, the presence of a serine-phenylalanine substitution (S431F) was identified in one individual. The S431F substitution, has been shown to confer significant levels of both organophosphate and carbamate resistance in other aphid species, and is now found for the first time in T. trifolii. We subsequently developed a simple polymerase chain reaction restriction fragment length polymorphism assays for the S431F mutation, using a TaqI restriction site destroyed by the S431F mutation. The novel diagnostic assay may support the implementation of Insecticide Resistance Management strategies, for the control of SAA in alfalfa crops in the Kingdom of Saudi Arabia, and other countries worldwide. PMID- 26278203 TI - Analyzing torquoselectivity in electrocyclic ring opening reactions of trans-3,4 dimethylcyclobutene and 3-formylcyclobutene through electronic structure principles. AB - The validity of maximum hardness, minimum electrophilicity and minimum polarizability principles is assessed to explain the phenomenon of torquoselectivity (inward and outward preference) in the conrotatory ring opening reactions of trans-3,4-dimethylcyclobutene into Z,Z- and E,E-butadienes and 3 formylcyclobutene into E- and Z-2,4-pentadienals. The hardness, average polarizability and electrophilicity profiles are computed along the intrinsic reaction coordinate and divided into three relevant stages. The transition states involved in the unfavorable inward conrotation of trans-3,4-dimethylcyclobutene and in the unfavorable outward conrotation of 3-formylcyclobutene are found to be higher in energy, softer, more electrophilic and more polarizable than the transition states corresponding to the torquoselective outward and inward conrotations, respectively. These observations are in conformity with the maximum hardness, minimum electrophilicity and minimum polarizability principles. The sharp changes in the local reactivity descriptors are also observed around the transition states in their respective profiles. PMID- 26278204 TI - Tuning the properties of the UiO-66 metal organic framework by Ce substitution. AB - Crystallisation of a mixed-metal form of the porous framework UiO-66 in which Zr is partially replaced by Ce produces a ligand-defective material, that contains some Ce(III) as well as a majority of Ce(IV). Infrared spectroscopy shows enhanced binding of methanol in the substituted material that leads to catalytic decomposition of the alcohol, which may be due to a combination of defects and redox activity. PMID- 26278206 TI - The effect of 7.2% hypertonic saline solution on echocardiographic parameters of healthy horses. AB - REASONS FOR PERFORMING STUDY: The cardiovascular effects and duration of action of hypertonic saline are not yet fully understood in the horse. OBJECTIVE: To determine the effects of hypertonic saline on cardiac measurements derived from echocardiography over a period of 90 min after infusion in euvolaemic and healthy horses. STUDY DESIGN: Experimental study. METHODS: Five healthy conscious euvolaemic horses were infused with 5 ml/kg bwt hypertonic saline via a jugular catheter over 1 h. Immediately prior to infusion and at 0, 20, 40, 60 and 90 min after the completion of the infusion, echocardiographic images were obtained from the right parasternal window. The left ventricular internal diameter at end diastole and left ventricular internal diameter in peak systole were measured and ventricular volume measurements were calculated by the Teicholz method. Data were analysed using a mixed effects model, which included horse as a random effect. The effect of observation time was assessed accounting for correlation between observations. RESULTS: Fractional shortening and ejection fraction increased significantly 40 min after completion of infusion. Left ventricular internal diameter at end diastole, end diastolic volume and stroke volume all followed the same pattern and were increased at 20, 40 and 60 min compared to preinfusion values. There were also significant differences between the 0 and 40, 40 and 90, 60 and 90 time points. Other parameters did not differ significantly between time points. CONCLUSIONS: Hypertonic saline increases end-diastolic and stroke volume for approximately 1 h after completion of a 60 min infusion in euvolaemic horses. This adds to the evidence available to clinicians regarding the duration of action of hypertonic saline. PMID- 26278208 TI - Dialysis Amyloid Deposition in the Aortic Valve and Its Association with Aortic Stenosis. AB - BACKGROUND: The relationship between dialysis amyloid (DA) deposition in the aortic valve (AV) and aortic stenosis (AS) is unknown. METHODS: This was a cross sectional study. AV specimens of dialysis patients (median vintage: 8.8 years) consecutively collected from cardiac surgeries (n = 56) or autopsies (n = 13) were examined by a board-certified pathologist blinded to clinical data. DAs were considered to be present if deposits were stained both by Congo red with apple green birefringence under polarized light and by anti-beta2-microblobulin antibody. Degree of deposition was graded as follows: Amyloid (-), no deposit; Amyloid (1+), occasional small deposits; Amyloid (2+), multiple small to large deposits or a single large deposit. Calcification was defined as a calcified deposit with a diameter >1 mm in the specimen. Severe AS (sAS) was defined as a mean gradient >50 mm Hg by echocardiogram. We examined the proportion of DAs and the association between DAs and the sAS. RESULTS: DAs were present in 71% (n = 49) of specimens and primarily co-localized with calcification. Non-dialysis related amyloid was found in one specimen. After excluding this specimen, sAS was associated with 'Amyloid (1+) and Calcification >1 mm' and 'Amyloid (2+) and Calcification >1 mm' (vs. 'Amyloid (-) and Calcification <=1 mm', odds ratios (ORs): 13.5 and 34.2, respectively). Furthermore, after adjustment for covariates, sAS was found to be associated with 'Amyloid (2+) and Calcification >1 mm' (OR: 24.3). CONCLUSIONS: DA deposition in the AV was prevalent among dialysis patients. DA deposition with accompanying calcification might contribute to the severity of AS. PMID- 26278207 TI - Novel evidence of association with nonsyndromic cleft lip with or without cleft palate was shown for single nucleotide polymorphisms in FOXF2 gene in an Asian population. AB - BACKGROUND: The forkhead box F2 gene (FOXF2) located in chromosome 6p25.3 has been shown to play a crucial role in palatal development in mouse and rat models. To date, no evidence of linkage or association has been reported for this gene in humans with oral clefts. METHODS: Allelic transmission disequilibrium tests were used to robustly assess evidence of linkage and association with nonsyndromic cleft lip with or without cleft palate for nine single nucleotide polymorphisms (SNPs) in and around FOXF2 in both Asian and European trios using PLINK. RESULTS: Statistically significant evidence of linkage and association was shown for two SNPs (rs1711968 and rs732835) in 216 Asian trios where the empiric P values with permutation tests were 0.0016 and 0.005, respectively. The corresponding estimated odds ratios for carrying the minor allele at these SNPs were 2.05 (95% confidence interval = 1.41, 2.98) and 1.77 (95% confidence interval = 1.26, 2.49), respectively. CONCLUSION: Our results provided statistical evidence of linkage and association between FOXF2 and nonsyndromic cleft lip with or without cleft palate. PMID- 26278209 TI - Thermoelectric Properties of Ga/Ag Codoped Type-III Ba24Ge100 Clathrates with in Situ Nanostructures. AB - Because of the low thermal conductivity and high electrical conductivity, type III Ba24Ge100 clathrates are potentially of interest as power generation thermoelectric materials for midto-high temperature operations. Unfortunately, their too high intrinsic carrier concentration results in a quite low Seebeck coefficient. To reduce the carrier concentration, we prepared a series of Ga/Ag codoped type-III Ba24Ge100 clathrate specimens by vacuum melting and subsequently compacted by spark plasma sintering (SPS). Doping Ga-Ag on the sites of Ge reduces the concentration of electrons and, at higher concentrations, also leads to the in situ formation of BaGe2 nanoprecipitates detected by the microstructural analysis. As a result of doping, the Seebeck coefficient increases, the thermal conductivity decreases, and the dimensionless figure of merit ZT reaches a value of 0.34 at 873 K, more than three times the value obtained with undoped Ba24Ge100. PMID- 26278210 TI - [Cosmesis and Body Image after Laparo-Endoscopic Single Site Donor Nephrectomy]. AB - Using a questionnaire, we objectively assessed the body image of donors who underwent conventional laparoscopic donor nephrectomy (L-DN) or laparoscopic single-site donor nephrectomy (LESS-DN). Subjects were 15 patients who underwent an L-DN and 15 who underwent an LESS-DN. The questionnaire consisted of the Body Image Questionnaire (BIQ), including a Body Image Scale (BIS) and Cosmetic Scale (CS), and a Photo-Series Questionnaire (PSQ). A higher score indicated a more favorable assessment, and patient scores were compared. Subjects were also asked which procedure they preferred if they had to undergo donor nephrectomy again. Pain was assessed by comparing the number of times an analgesic was administered during hospitalization. The average BIS score was 18.7 points (out of 20) for patients who underwent an L-DN and 19.5 points for patients who underwent an LESS DN ; those who underwent an LESS-DN had a significantly higher score (p=0.03). Patients who underwent an L-DN had a median CS score of 17.5 points (out of 24) while patients who underwent an LESS-DN had a median CS score of 19.1 points ; those who underwent an LESS-DN had a higher score, but the difference in average CS scores was not significant (p=0.123). The average PSQ score was 7.1 points for patients who underwent an L-DN and 8.8 points for patients who underwent an LESS DN ; the higher score for LESS-patients was statistically significant (p=0.01). Patients who underwent an L-DN were administered an analgesic a median of 4 times during hospitalization (range : 3-10 times) while patients who underwent an LESS DN were administered an analgesic a median of 2 times (range : 0-4 times), which was significantly less (p=0.01). Patients who underwent LESS-DN had a better body image and better cosmetic appearance than those who underwent LDN, thus indicating the usefulness of LESS-DN. However, a more prospective larger study needs to be performed. PMID- 26278211 TI - [Epithelioid Angiomyolipoma of the Kidney: A Case Report]. AB - Herein we report a case of epithelioid angiomyolipoma of the kidney which is a rare subtype of angiomyolipoma. A 68-year-old man without a history of tuberous sclerosis complex (TSC) was referred to our department with a 40 * 84 mm left renal tumor incidentally detected by computed tomography. Computed tomography demonstrated a left renal heterogeneous mass which was enhanced at the early phase and washed out at the late phase. A tumor thrombus was seen extending into the main renal vein. No metastatic disease was evident. Thus, on the diagnosis of renal cell carcinoma, the patient underwent a left radical nephrectomy. Pathological examination showed that this tumor was composed predominantly of epithelioid cells, with a few blood vessels and adipose tissue and was diagnosed as epithelioid angiomyolipoma. He shows no disease progression for 6 months after the operation. PMID- 26278212 TI - [A Case of Localized Amyloidosis of the Ureter Diagnosed by Ureter Biopsy Using a Ureteroscope]. AB - A 42-year-old female visited our hospital with the chief complaint of macrohematuria and left lateroabdominal pain. Computed tomography and retrograde pyelogram showed left hydronephroureter and obstructive uropathy which was 20 mm in diameter in the middle ureter. Urine cytology was negative. Ureter biopsy revealed amyloidosis. Our diagnosis was localized amyloidosis of the ureter, because amyloid was not found in other places in her whole body inspection. Partial ureterectomy was performed. Left renal function was preserved. The patient has been free of recurrence for 18 months after surgery. PMID- 26278213 TI - [A Case Report of 2,8-Dihydroxyadenine Stone]. AB - Here we report a case of a 2,8-dihydroxyadenine (2,8-DHA) stone. A 48-year-old woman arrived at our hospital with left flank pain. She was diagnosed with a left ureteral stone. Extracorporeal shock wave lithotripsy (ESWL) was tried, but the left ureteral stone was radiolucent and ESWL was not effective. Transurethral ureterolithotripsy (TUL) was successful. An analysis of the stone revealed 2,8 DHA. A 2,8-DHA stone is caused by adenine phosphoribosyltransferase (APRT) deficiency. By genetic tests, she was diagnosed with APRT deficiency. PMID- 26278214 TI - [Vesicoappendiceal Fistula: A Case Report]. AB - A 65-year-old man had been aware of pieces of food occasionally in the urine since February 2008. In November 2010, he came to an outpatient clinic with high fever and cloudy urine and was diagnosed with urinary tract infection. Because he had fecaluria, interconnection between urinary bladder and digestive tract was suspected. Although excretory urography showed no remarkable findings, an outflow of contrast media into the appendix was demonstrated in the cystography. By cystoscopy, the fistula hole was confirmed on the posterior wall of the bladder and inflow of feces from the hole was noticed. Operation was performed under the diagnosis of vesicoappendiceal fistula. The appendix was adhesive to the ileum, the right side of the bladder and the upper side of the rectum, and an en bloc resection was performed. Because the fecalith existed near the fistula, appendicitis appeared to induce inflammatory change and abscess formation around the appendix, and the abscess might have perforate into the bladder. PMID- 26278215 TI - [An Adult Case of Transperineal Repair of Congenital Rectourethral Fistula Using Gracilis Muscle Flap Interposition]. AB - A man in his 50s was referred to our hospital after recurrent severe urinary tract infection. He had undergone anoplasty for anorectal malformation during early infancy. He noticed urinary leakage from the anus for a long time. Under diagnosis of congenital rectourethral fistula, we performed fistula closure. The fistula was transsected via transperineal incision and each stump was closed. A gracilis muscle flap approximately 30 cm long was harvested from the left thigh, brought into the deepest part between the separated rectum and urethra through a subcutaneous tunnel and fixed there. The urinary leakage from the anus disappeared, and the infection resolved. Application of gracilis muscle flap for congenital diseases is rare, but was useful in the present case. PMID- 26278217 TI - [Transvesical Removal of Seminal Vesicle Cystadenoma]. AB - Primary tumors of the seminal vesicles are extremely rare. There have been 25 reports of this tumor from overseas and most cases are cystadenoma. We report a case of seminal vesicle cystadenoma in a 70-year-old man who presented with lower abdominal pain and urinary frequency. A digital rectal examination detected a projecting and hard mass in the right side of the prostate. Magnetic resonance imaging (MRI) showed a 15 cm multiple cystic mass continuous with the right seminal vesicle. A transrectal needle biopsy revealed benign tissue. The tumor was resected using an open transvesical approach that enabled full exposure of the seminal vesicle without damaging the nerves and blood supply of the bladder. Pathology was consistent with a benign seminal vesicle cystadenoma. We describe the natural history, pathology,and surgical approach in this case. PMID- 26278216 TI - [Primary Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma with Large Cell Transformation of the Prostate : A Case Report]. AB - Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the prostate is rare. MALT lymphoma with large cell transformation like a diffuse large B-cell lymphoma (DLBCL) of the prostate is extremely rare. To the best of our knowledge, only one case has been previously reported. A 65-year-old man with difficulty on urination was referred to our department, in April 2014, because of abnormal findings of magnetic resonance imaging (MRI) and positron emission tomography computed tomography imaging. Routine laboratory tests including prostate specific antigen and soluble interletkin-2 recepter were within normal limits, and the physical examination was unremarkable. In July 2007 and August 2009, he was submitted for a transrectal prostate biopsy, and then a histological examination for chronic prostatitis. In addition to the biopsy, transurethral resection of the prostate was performed. Histological examination revealed primary MALT lymphoma with large cell transformation of the prostate. Complete clinical investigation, including bone marrow biopsy, did not show any involvement of other sites by lymphoma, he received 3 cycles of chemotherapy consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) followed by radiation therapy with a total dose of 46 Gy. The patient has been in complete remission for 6 months after the chemoradiation therapy. PMID- 26278218 TI - Auditing Neonatal Intensive Care: Is PREM a Good Alternative to CRIB for Mortality Risk Adjustment in Premature Infants? AB - BACKGROUND: Comparing outcomes at different neonatal intensive care units (NICUs) requires adjustment for intrinsic risk. The Clinical Risk Index for Babies (CRIB) is a widely used risk model, but it has been criticized for being affected by therapeutic decisions. The Prematurity Risk Evaluation Measure (PREM) is not supposed to be prone to treatment bias, but has not yet been validated. OBJECTIVES: We aimed to validate the PREM, compare its accuracy to that of the original and modified versions of the CRIB and CRIB-II, and examine the congruence of risk categorization. METHODS: Very-low-birth-weight (VLBW) infants with a gestational age (GA) <33 weeks, who were admitted to NICUs in Baden Wurttemberg from 2003 to 2008, were identified from the German neonatal quality assurance program. CRIB, CRIB-II and PREM scores were calculated and modified. Omitting variables that directly reflected therapeutic decisions [the applied fraction of inspired oxygen (FiO2)] or that may have been prone to early treatment bias (base excess and temperature), non-NICU-therapy-influenced scores were obtained. Score performance was assessed by the area under their ROC curve (AUC). RESULTS: The CRIB showed the largest AUC (0.89), which dropped significantly (to 0.85) after omitting the FiO2. The PREM birth condition model, PREM(bcm) (AUC 0.86), and the PREM birth model, PREM(bm) (AUC 0.82), also demonstrated good discrimination. PREM(bm) was superior to other non-therapy affected scores and to GA, particularly in infants with <750 g birth weight. Congruence of risk categorization was low, especially among higher-risk cases. CONCLUSIONS: The CRIB score had the largest AUC, resulting from its inclusion of FiO2. PREM(bm), as the most accurate score among those unaffected by early treatment, seems to be a good alternative for strict risk adjustment in NICU auditing. It could be useful to combine scores. PMID- 26278219 TI - MicroRNA-203 Regulates Growth and Metastasis of Breast Cancer. AB - BACKGROUNDS/AIMS: MicroRNAs (MiRNAs) control many biological events and play critical roles in the development of tumor. Among all miRNAs, miR203 has been recently shown to have an inhibitory effect on prostate cancer. However, its involvement in the carcinogenesis of breast cancer has not been reported. METHODS: We examined the levels of miR203 in the breast cancer from the patients compared to the paired normal breast tissue. We also examined the levels of miR203 in several commonly used breast cancer cell lines. The effects of overexpression or depletion of miR203 on breast cancer cell growth were analyzed by a MTT assay, and on breast cancer cell invasion were examined by a scratch wound healing assay and a transwell cell migration assay. MiR203-targeted genes were analyzed by Western blot. RESULTS: We detected significantly lower levels of miR203 in the breast cancer from the patients compared to the paired normal breast tissue. Moreover, the levels of miR203 were significantly lower in breast cancer tissue from the patients with cancer metastasis. Decreased miR203 levels were detected in all examined breast cancer lines. Overexpression of miR203 inhibited breast cancer cell growth and invasion, while antisense-mediated inhibition of miR203 enhanced cancer cell growth and invasion. Further analyses show that miR203 may inhibit cell growth through decreasing cell-cycle activator cyclinD2 and CDK6, increasing cell-cycle suppressor p21 and p27, and increasing apoptosis-associated protein Bcl-2. MiR203 may also inhibit cell metastasis through suppressing matrix metalloproteinase 2 (MMP2), MMP7 and MMP9. CONCLUSION: Our data thus highlight miR203 as a novel therapeutic target for breast cancer. PMID- 26278221 TI - Adequacy of Fine-Needle Aspiration Cytology for Breast Lesions: The SurePath(r) Liquid-Based Technique versus Conventional Smears. AB - OBJECTIVE: We aimed to assess the cytological findings from fine-needle aspiration (FNA) of breast lesions with conventional smear (CS) and SurePath(r) (SP) cytology. STUDY DESIGN: This was a cross-sectional study of women who underwent FNA from January 2012 to June 2013 for breast lesions with benign ultrasonography impressions in Fortaleza, Brazil. Two groups were formed. The first was composed of 102 samples subjected to CS and the second of 65 samples subjected to SP. The number of smears, the cellularity and the diagnostic hypotheses were compared. Fisher's exact tests with 95% confidence intervals were applied. RESULTS: The women ranged in age from 22 to 75 years. SP cytology indicated greater cellularity than CS for the cystic lesions (p < 0.05). In the CS group, 72.5% of the samples required 3-4 slides, but in the SP group, only 9.2% required a second slide. The cellularity of the cystic samples was significantly greater with the SP method (p < 0.01). CONCLUSION: In FNA cytology of the breast, SP is a tool that is comparable to CS, but with the added benefits of better cellularity results for cystic lesions and requiring fewer slides for analysis. PMID- 26278220 TI - Progress in adjuvant chemotherapy for breast cancer: an overview. AB - Breast cancer is the most common cause of cancer and cancer death worldwide. Although most patients present with localized breast cancer and may be rendered disease-free with local therapy, distant recurrence is common and is the primary cause of death from the disease. Adjuvant systemic therapies are effective in reducing the risk of distant and local recurrence, including endocrine therapy, anti-HER2 therapy, and chemotherapy, even in patients at low risk of recurrence. The widespread use of adjuvant systemic therapy has contributed to reduced breast cancer mortality rates. Adjuvant cytotoxic chemotherapy regimens have evolved from single alkylating agents to polychemotherapy regimens incorporating anthracyclines and/or taxanes. This review summarizes key milestones in the evolution of adjuvant systemic therapy in general, and adjuvant chemotherapy in particular. Although adjuvant treatments are routinely guided by predictive factors for endocrine therapy (hormone receptor expression) and anti-HER2 therapy (HER2 overexpression), predicting benefit from chemotherapy has been more challenging. Randomized studies are now in progress utilizing multiparameter gene expression assays that may more accurately select patients most likely to benefit from adjuvant chemotherapy. PMID- 26278222 TI - Organized Self-Management Support Services for Chronic Depressive Symptoms: A Randomized Controlled Trial. AB - OBJECTIVE: This study aimed to determine whether a self-management support service was more effective than treatment as usual in reducing depressive symptoms and major depressive episodes and increasing personal recovery among individuals with chronic or recurrent depressive symptoms. METHODS: The study was a randomized controlled trial of a self-management support service consisting of depression self-management training, recovery coaching, and care coordination. The 18-month intervention included regular telephone or in-person contacts with a care manager and a structured group program co-led by a professional therapist and a trained peer specialist. Intervention (N=150) and control (N=152) participants ages >= 18 with chronic or recurrent depressive symptoms were recruited from five clinics in Seattle, Washington. Outcome measures included the Hopkins Symptom Checklist depression scale, the Recovery Assessment Scale, the Patient-Rated Global Improvement scale, and the percentage of participants with a major depressive episode. Interviewers were masked to treatment condition. RESULTS: Repeated-measures estimates of the long-term effect of the intervention versus usual care (average of the six-, 12-, and 18-month outcomes adjusted for age, gender, and site) indicated that intervention participants had less severe symptoms (p=.002) and higher recovery scores (p=.03), were less likely to be depressed (odds ratio [OR]=.52, p=.001), and were more likely to be much improved (OR=1.96, p=.001). CONCLUSIONS: These findings support providing regular outreach care management and a self-care group offering a combined behavioral and recovery oriented approach for people with chronic or recurrent depressive symptoms. PMID- 26278223 TI - Factors Associated With Civilian Employment, Work Satisfaction, and Performance Among National Guard Members. AB - OBJECTIVE: Employment is a vital part of the postdeployment return to civilian life. This study investigated factors associated with employment-related outcomes (employment status, self-reported work performance, and self-reported work satisfaction) among National Guard members returning from Operation Enduring Freedom, Operation Iraqi Freedom, or Operation New Dawn deployments. METHODS: The sample consisted of 1,151 National Guard service members who had returned from overseas deployments approximately six months earlier. Bivariate and multivariable analyses were performed to examine associations between predictors and employment-related outcome variables. RESULTS: Higher-risk alcohol use was associated with reduced odds of being employed as well as with lower ratings of work satisfaction, whereas psychiatric symptom load was associated with lower self-reported work performance and work satisfaction ratings. Perceived social resources were associated with higher self-reported work performance and work satisfaction, whereas better physical functioning was associated with better self reported work performance. CONCLUSIONS: Policy makers and clinicians may need to consider and assess alcohol use among unemployed National Guard members. They may also need to consider psychiatric symptom load and physical functioning among employed service members who perceive poor work performance and have low work satisfaction. Further research is needed on causal links between these predictors and employment outcomes. PMID- 26278224 TI - Opting Out of Medicaid Expansion: Impact on Encounters With Behavioral Health Specialty Staff in Community Health Centers. AB - OBJECTIVE: This study examined how state decisions not to expand Medicaid have affected behavioral health services utilization in health centers. Because health center revenues are adversely affected, the ability to provide on-site nonrequired services, such as specialty mental health and substance abuse treatment services, is compromised. METHODS: Using 2012 Uniform Data System data and the projected health center insurance case mix in 2020, the authors estimated the amount of additional revenue that could accrue to health centers if all states were to expand Medicaid by 2020. Using the estimated percentage of total revenues supporting the provision of specialty behavioral treatment services, the authors also estimated the number of encounters with behavioral health specialists that might be possible in 2020 if all states expand Medicaid by then. State-specific estimates are provided. RESULTS: If all states expand Medicaid by 2020, it is estimated that nearly $230 million in additional revenue could accrue to health centers in states that opted out of expanding Medicaid in 2014. An estimated $11.3 million would likely be used for mental health services and $1.6 million might be used to provide substance use disorder services. This translates to over 70,500 additional encounters that could occur with behavioral health specialists if all states expand Medicaid by 2020. CONCLUSIONS: On-site behavioral health services are needed in health centers. However, financial constraints might limit the ability of health centers to provide on-site behavioral health services, particularly in states opting out of Medicaid expansion. PMID- 26278225 TI - Growing Use of Mental and General Health Care Services Among Older Veterans With Mental Illness. AB - OBJECTIVE: National data from Veterans Health Administration (VHA) electronic medical records were used to examine rates of mental illness and service use among older veterans since mental health care transformation efforts were implemented in 2005. METHODS: Data were extracted from VHA electronic medical records for each fiscal year from 2005 through 2013 for veterans ages 65 and older. Among those receiving any health care services, the number and proportion treated for a confirmed mental illness and the utilization of non-mental health care services were identified. RESULTS: In 2013, 2.6 million older veterans utilized services in VHA, 14% of whom had a confirmed mental illness, which was a 57% increase from 2005. Older veterans with confirmed mental illness accounted for a sizable and growing proportion of non-mental health service utilization. CONCLUSIONS: Preparing the workforce to address the mental health needs of older veterans and nonveterans is essential. PMID- 26278226 TI - Using the WHODAS 2.0 to Assess Functioning Among Veterans Seeking Compensation for Posttraumatic Stress Disorder. AB - OBJECTIVE: One of the major changes in DSM-5 was removal of the Global Assessment of Functioning (GAF). To determine whether the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) is a suitable replacement for the GAF, this study compared how well the WHODAS 2.0 and the GAF measured functional impairment and other phenomena related to posttraumatic stress disorder (PTSD) among veterans applying for financial compensation (service connection) for PTSD. METHODS: Clinicians evaluating veteran claimants administered the Clinician Administered PTSD Scale (CAPS) and the WHODAS 2.0 to 177 veterans during their evaluations. Veterans also completed the Inventory of Psychosocial Functioning (IPF), a self-report measure of functional impairment, and received a GAF rating from the examiner. Actual benefit determinations and ratings were obtained. RESULTS: Confirmatory factor analyses demonstrated that the WHODAS 2.0 and the IPF were stronger indicators of a latent variable reflecting functioning compared with the GAF. In receiver operating characteristic curve analyses, the WHODAS 2.0, IPF, and GAF all displayed similar ability to identify veterans with PTSD related impairment assessed by the CAPS. Compared with the GAF, the WHODAS 2.0 and IPF were less strongly related to PTSD symptom severity and disability ratings by the U.S. Department of Veterans Affairs, but these variables are typically influenced by GAF scores. CONCLUSIONS: The WHODAS 2.0 and IPF are acceptable replacements for the GAF and can be used to assess functional impairment among veterans seeking compensation for PTSD. PMID- 26278227 TI - Multifamily Group Psychoeducation in New York State: Implementation and Fidelity Outcomes. AB - OBJECTIVE: The study examined implementation outcomes from a large state initiative to support dissemination of multifamily group (MFG) psychoeducation in outpatient mental health settings. METHODS: Thirty-one sites participated in the project. Baseline training in the MFG model was followed by monthly expert consultation delivered in either a group (16 sites) or individual format (15 sites). Research staff assessed fidelity to the MFG model by telephone at baseline and 12, 18, and 24 months and documented time to completion of three key milestones: holding a family joining session, a family educational workshop, and an MFG meeting. RESULTS: Intent-to-train analyses found that 12 sites (39%) achieved high fidelity to the MFG model, and 20 (65%) achieved moderate or high fidelity. Mean scores on the Family Psychoeducation Fidelity Assessment Scale increased over time. Twenty-five sites (81%) conducted at least one joining session, and 20 (65%) conducted at least one MFG. Mean+/-SD time from baseline to the first group was 11.75+/-4.78 months. Programs that held the first joining session within four to 12 months after training were significantly more likely than programs that did not to conduct a group (p<.05). No significant differences were found by consultation format. CONCLUSIONS: Implementation of moderate- to high-fidelity MFG programs in routine outpatient mental health settings is feasible. Sites that moved very quickly or very slowly in early implementation stages were less likely to be successful in conducting an MFG. More research on the efficiency and effectiveness of consultation formats is needed to guide future implementation efforts. PMID- 26278228 TI - Intensity of Offending Following State Prison Release Among Persons Treated for Mental Health Problems While Incarcerated. AB - OBJECTIVE: This study examined a range of demographic, clinical, and criminal history factors as they relate to the intensity of offending for up to two years postrelease. METHODS: This study drew on data from 1,438 individuals released from Massachusetts state prisons between 2007 and 2009 who, while incarcerated, received treatment from the prisons' mental health services and were followed for 24 months postrelease. These data were used to explore predictive factors related to the intensity of criminal justice involvement, defined as number of arrests in the two-year follow-up period. RESULTS: Predictors of subsequent arrests included number of previous incarcerations and black race. Protective factors included older age, supervision by parole, and a drug-related or person-related governing offense on previous arrest. Clinical symptoms were not related to incidence of postrelease arrests. CONCLUSIONS: This study identified factors related to criminal history, such as type of charge, that were associated with the intensity of subsequent criminal justice involvement. These findings have not been reported in previous studies, perhaps because intensity of offending as opposed to a different dependent variable was used to measure criminal justice involvement. Further investigation should focus on whether the type of previous offense is related to postrelease risk factors for recidivism. PMID- 26278229 TI - An Examination of Eligibility Decisions in New York State's Assisted Outpatient Treatment. AB - OBJECTIVE: The objective of this study was to compare assisted outpatient treatment (AOT) eligibility characteristics among participants receiving community treatment through AOT and non-AOT referrals. METHODS: A total of 131 AOT and non-AOT charts were reviewed from three sites within one treatment agency in New York City. Intake information was coded for AOT eligibility information, suicide history, and risk of future violence according to the Historical Clinical Risk Management-20, version 3 (HCR-20V3), instrument. RESULTS: No significant differences were found between groups for measurable AOT eligibility criteria. Compared with non-AOT participants, the participants referred through AOT scored significantly higher on HCR-20V3 for risk of future violence; however, most charts, including almost half of AOT participants, received low risk ratings. CONCLUSIONS: Study findings raise questions about why some individuals, and not others, are referred to AOT in New York City. PMID- 26278230 TI - Evaluating START NOW: A Skills-Based Psychotherapy for Inmates of Correctional Systems. AB - OBJECTIVE: This study investigated whether higher attendance in a skills-based group therapy program designed for inmates was associated with fewer rule infractions as reflected in the number of disciplinary reports received in a state correctional system. METHODS: Administrative data were provided by the Connecticut Department of Correction and Correctional Managed Health Care at UConn Health, the system's health care organization. This was a retrospective cohort analysis of START NOW program participation events from 2010 through 2013 (N=946). Participants were adult male and female inmates, both sentenced and unsentenced, with and without recorded psychiatric diagnoses. The number of disciplinary reports was documented for up to six months after program participation. Incident rate ratios are presented from zero-inflated negative binomial regression models. Predictive margins examined variation in the effect of sessions attended on disciplinary reports in the postprogram period across security risk groups and primary psychiatric diagnosis groups. RESULTS: For each additional session of START NOW completed, a 5% reduction was noted in the incident rate of disciplinary reports. The effect of program participation was robust to all model considerations. Inmates with higher overall security scores appear to benefit most from program participation. The program was also found to be effective across primary psychiatric diagnosis classifications. CONCLUSIONS: START NOW was shown to be an effective treatment option for reducing disciplinary infractions by inmates. PMID- 26278232 TI - School-Based Behavioral Health Service Use and Expenditures for Children With Autism and Children With Other Disorders. AB - OBJECTIVE: This study compared use of and associated expenditures for Medicaid reimbursed school-based and out-of-school services for children with autism spectrum disorder (ASD) and those with other psychiatric disorders. METHODS: Philadelphia County Medicaid claims were used to identify children ages five to 17 who received behavioral health services through Medicaid any time between October 2008 and September 2009 (N=24,271). Children were categorized into four diagnostic groups: autism spectrum disorder (ASD), conduct disorder or oppositional defiant disorder (conduct-ODD), attention-deficit hyperactivity disorder (ADHD), and other psychiatric disorders. Logistic regression analysis compared use of in-school and out-of-school behavioral health services between children with ASD and children with other psychiatric disorders. Generalized linear models with gamma distribution were used to estimate differences in Medicaid expenditures for in-school and out-of-school services and total Medicaid expenditures for both service types by disorder, with adjustments for age, sex, and race-ethnicity. RESULTS: The most common diagnosis was ADHD (40%); 35% had other psychiatric disorders, 21% had conduct-ODD, and 4% had ASD. A significantly greater proportion of children with ASD (52%) received in-school behavioral health services (conduct-ODD, 5%; ADHD, 8%; and other psychiatric disorders, 1.7%) Per-child expenditures for both school-based and out-of-school behavioral health services were significantly higher for children with ASD than for children in the other groups. CONCLUSIONS: Medicaid represents an important source of in school and out-of-school care for children with ASD and their families. States that expand Medicaid under the Affordable Care Act should give careful consideration to covering school-based mental health services for children with ASD. PMID- 26278233 TI - Characteristics of Individuals With Mental Illness in Tokyo Homeless Shelters. AB - OBJECTIVE: Japan has the largest number of psychiatric beds in the world and has been in the process of deinstitutionalization since 2004. The majority of psychiatric inpatients are elderly long-term patients, who are at risk of homelessness after they are discharged. There is little information about homeless people with mental illnesses in Japan, and the aim of this study was to describe characteristics of people with a mental illness in homeless shelters in Tokyo. METHODS: A face-to-face survey was conducted from December 2012 to March 2013 by the staff of a nonprofit organization (NPO) that helps socially isolated persons. Of the 1,056 people who received help during the study period, 684 completed the survey. RESULTS: Eighteen percent of the 684 survey participants had a mental illness. Of the 210 individuals who lived in shelters, one-third had a mental illness. The mean age of shelter users with mental illness was 64.9; they tended to be referred from hospitals, and their mental well-being was poorer than other NPO service users in the study. Among the service users with mental illness, those living in shelters were older than those living in the community and more likely to have a history of trouble with alcohol, poor family relationships, and impaired instrumental activities of daily living. CONCLUSIONS: Unmet mental health needs were noted among discharged hospital patients living in Tokyo homeless shelters. An integrated and community-based support system with more effective health care delivery, including critical time interventions, is needed. PMID- 26278231 TI - Depression Remission Rates Among Older Black and White Adults: Analyses From the IRL-GREY Trial. AB - OBJECTIVE: This study explored whether older black and white adults with major depressive disorder differed in rates of remission or attrition during open-label treatment with venlafaxine and supportive care. METHODS: A total of 47 black (10%) and 412 white (90%) adults age >=60 were treated with open-label venlafaxine extended-release (<=300 mg per day) for 12-14 weeks during the initial phase of an multisite, randomized, placebo-controlled augmentation trial. Participants were help-seeking older adults with nonpsychotic major depressive disorder (single or recurrent episode) referred from specialty clinics, primary care practices, advertisements, and research programs. Remission was defined as a Montgomery-Asberg Depression Rating Scale score of <=10 for two consecutive assessments at the end of 12 weeks. Kaplan-Meier curves displayed time to dropout and time to initial remission. Cox proportional hazards models assessed differences in attrition and remission rates. RESULTS: Black participants had greater baseline general medical comorbidity, worse physical health-related quality of life, and poorer cognitive function than white participants. White participants were more likely to have received an adequate trial of antidepressant and psychotherapy before study entry. Baseline depression severity, depression duration, age at onset, and recurrence history did not differ between groups. The groups had similar final doses of venlafaxine and similar rates of attrition and remission. Side-effect profiles were comparable between the groups. CONCLUSIONS: Despite greater medical comorbidity, lower cognitive function, and less adequate prior exposure to antidepressant treatment and psychotherapy, black participants were no more likely to discontinue antidepressant pharmacotherapy and experienced a rate of remission comparable to white participants. PMID- 26278234 TI - Challenging the Stigma of Mental Illness: Different Agendas, Different Goals. AB - This Open Forum describes two agendas for addressing stigma surrounding mental illness: the services agenda, which aims to increase care seeking by decreasing stigma, and the rights agenda, which aims in the spirit of other civil rights efforts to eradicate the discrimination felt by people with mental illness. The two agendas developed independently and tend to embrace different approaches to effecting change in the population. These differences and directions for future research are described. PMID- 26278235 TI - Development and Implementation of an Ambulatory Integrated Care Pathway for Major Depressive Disorder and Alcohol Dependence. AB - Integrated care pathways (ICPs) provide an approach for delivering evidence-based treatment in a hospital setting. This column describes the development and pilot implementation in a clinical setting of an ICP for patients with concurrent major depressive disorder and alcohol dependence at the Centre for Addiction and Mental Health (CAMH), an academic tertiary care hospital, in Toronto, Canada. The ICP methodology includes evidence reviews, knowledge translation, process reengineering, and change management. Pilot results indicate high patient satisfaction, evidence of symptom improvement, and excellent retention. PMID- 26278236 TI - Ularitide: a natriuretic peptide candidate for the treatment of acutely decompensated heart failure. AB - Treatment for acutely decompensated heart failure (ADHF) has not changed much in the last two decades. Currently available therapies have variable efficacy and can be associated with adverse outcomes. Natriuretic peptides properties include diuresis, natriuresis, vasorelaxation, inhibition of renin-angiotensin aldosterone system, and are thus chosen in the treatment of ADHF. Two forms of natriuretic peptides are currently available for the treatment of ADHF. Urodilatin (INN: ularitide) represents another member of the natriuretic peptide family with a unique molecular structure that may provide distinct benefits in the treatment of ADHF. Early clinical exploratory and Phase II studies have demonstrated that ularitide has potential cardiovascular and renal benefits. Ularitide is currently being tested in the Phase III TRUE-AHF clinical study. TRUE-AHF has features that may be different when compared with other recent outcome studies in ADHF. These distinct differences aim to maximize clinical effects and minimize potential adverse events of ularitide. However, whether this rationale translates into a better outcome needs to be awaited. PMID- 26278237 TI - Energy-Driven Kinetic Monte Carlo Method and Its Application in Fullerene Coalescence. AB - Mimicking the conventional barrier-based kinetic Monte Carlo simulation, an energy-driven kinetic Monte Carlo (EDKMC) method was developed to study the structural transformation of carbon nanomaterials. The new method is many orders magnitude faster than standard molecular dynamics or Monte Marlo (MC) simulations and thus allows us to explore rare events within a reasonable computational time. As an example, the temperature dependence of fullerene coalescence was studied. The simulation, for the first time, revealed that short capped single-walled carbon nanotubes (SWNTs) appear as low-energy metastable structures during the structural evolution. PMID- 26278238 TI - Parameters Affecting I-V Hysteresis of CH3NH3PbI3 Perovskite Solar Cells: Effects of Perovskite Crystal Size and Mesoporous TiO2 Layer. AB - Current-voltage (I-V) characteristics of CH3NH3PbI3 perovskite solar cells are studied using a time-dependent current response with stepwise sweeping of the bias voltage. Compared with the crystalline Si solar cell showing time independent current at a given bias voltage, the perovskite solar cells exhibit time-dependent current response. The current increases with time and becomes steady at forward scan from short-circuit to open-circuit, whereas it is decayed and saturated with time at reverse scan from open-circuit to short-circuit. Time dependent current response eventually leads to I-V hysteresis depending on the scan direction and the scan rate. Crystal size of CH3NH3PbI3 and the mesoporous TiO2 (mp-TiO2) film are found to influence I-V hysteresis, where the I-V hysteresis is alleviated as crystal size increases and in the presence of mp TiO2. The capacitance observed at low frequency (0.1 to 1 Hz), associated with dipole polarization, tends to diminish as size of perovskite and mp-TiO2 layer thickness increases, which suggests that the origin of hysteresis correlates to the capacitive characteristic of CH3NH3PbI3 and the degree of hysteresis depends strongly on perovskite crystal size and mesoporous TiO2 layer. PMID- 26278239 TI - Optical Sensitivity Gain in Silica-Coated Plasmonic Nanostructures. AB - Ultrathin films of silica realized by sol-gel synthesis and dip-coating techniques were successfully applied to predefined metal/polymer plasmonic nanostructures to spectrally tune their resonance modes and to increase their sensitivity to local refractive index changes. Plasmon resonance spectral shifts up to 100 nm with slope efficiencies of ~8 nm/nm for increasing layer thickness were attained. In the ultrathin layer regime (<10 nm), which could be reached by suitable dilution of the silica precursors and optimization of the deposition speed, the sensitivity of the main plasmonic resonance to refractive index changes in aqueous solution could be increased by over 50% with respect to the bare plasmonic chip. Numerical simulations supported experimental data and unveiled the mechanism responsible for the optical sensitivity gain, proving an effective tool in the design of high-performance plasmonic sensors. PMID- 26278240 TI - Minimizing Electron-Hole Recombination on TiO2 Sensitized with PbSe Quantum Dots: Time-Domain Ab Initio Analysis. AB - TiO2 sensitized with quantum dots (QDs) gives efficient photovoltaic and photocatalytic systems due to high stability and large absorption cross sections of QDs and rapid photoinduced charge separation at the interface. The yields of the light-induced processes are limited by electron-hole recombination that also occurs at the interface. We combine ab initio nonadiabatic molecular dynamics with analytic theory to investigate the experimentally studied charge recombination at the PbSe QD-TiO2 interface. The time-domain atomistic simulation directly mimics the laser experiment and generates important details of the recombination mechanism. The process occurs due to coupling of the electronic subsystem to polar optical modes of the TiO2 surface. The inelastic electron phonon scattering happens on a picosecond time scale, while the elastic scattering takes 40 fs. Counter to expectations, the donor-acceptor bonding strengthens at an elevated temperature. An analytic theory extends the simulation results to larger QDs and longer QD-TiO2 bridges. It shows that the electron-hole recombination rate decreases significantly for longer bridges and larger dots and that the main effect arises due to reduced donor-acceptor coupling rather than changes in the donor-acceptor energy gap. The study indicates that by varying QD size or ligands one can reduce charge losses while still maintaining efficient charge separation, providing design principles for optimizing solar cell design and increasing photon-to-electron conversion efficiencies. PMID- 26278241 TI - Chemical Reactions Triggered Using Electrons Photodetached from "Clean" Distributions of Anions Deposited in Cryogenic Matrices via Counterion Codeposition. AB - Application of matrix isolation spectroscopy to ionic species is typically complicated by the presence of neutral contaminants during matrix deposition. Herein we demonstrate that simultaneous deposition of balanced currents of counterions with mass-selected ions of interest generates "clean" distributions of matrix-isolated metal carbonyl anions, where the only bands appearing in the CO-stretching region of the vibrational spectrum arise from ions. (Neutrals are initially absent.) Photodetachment by mild irradiation with visible light leads to complete conversion of the anions into their corresponding neutral species. The photodetached electrons, in turn, initiate covalent chemistry, inducing C-C bond formation following electron-capture by CO van der Waals dimers to produce trans-OCCO(-). The initial clean distribution of ions enables clear connections to be drawn between the spectral changes occurring at each experimental step, thus demonstrating the potential of the counterion codeposition technique to facilitate detailed studies of chemistry involving ions and electron transfer in cryogenic matrices. PMID- 26278242 TI - Assessment of Hot-Carrier Effects on Charge Separation in Type-II CdS/CdTe Heterostructured Nanorods. AB - Charge separation in semiconducting materials is an essential process that determines the efficiency of photovoltaic devices and photocatalysts. Herein, we report the charge-separation dynamics in type-II CdS/CdTe heterostructured nanorods revealed by femtosecond transient-absorption (TA) measurements with a broad-band white-light probe. Under selective excitation of the CdTe segment, bleaching signals at the band gap energy of CdS were clearly observed with a rise component on a subpicosecond time scale, which indicates efficient electron transfer from CdTe to CdS. The pump-energy dependence of the TA dynamics shows that hot electrons rapidly relax to the bottom of the conduction band of CdTe, and then the electrons transfer to the CdS segment. PMID- 26278243 TI - Plasmonic Optical Tweezers toward Molecular Manipulation: Tailoring Plasmonic Nanostructure, Light Source, and Resonant Trapping. AB - This Perspective describes recent progress in optical trappings of nanoparticles based on localized surface plasmon. This plasmonic optical trapping has great advantages over the conventional optical tweezers, being potentially applicable for a molecular manipulation technique. We review this novel trapping technique from the viewpoints of (i) plasmonic nanostructure, (ii) the light source for plasmon excitation, and (iii) the polarizability of the trapping target. These findings give us future outlook for plasmonic optical trapping. In addition to a brief review, recent developments on plasmonic optical trapping of soft nanomaterials such as proteins, polymer chains, and DNA will be discussed to point out the important issue for further development on this trapping method. Finally, we explore new directions of plasmonic optical trapping. PMID- 26278244 TI - Luminescence Properties of Compressed Tetraphenylethene: The Role of Intermolecular Interactions. AB - Mechanochromic materials with aggregation-induced enhanced emission (AIEE) characteristic have been intensively expanded in the past few years. In general, intermolecular interactions invariably alter photophysical processes, while their role in the luminescence properties of these AIEE-active molecules is difficult to fully recognize because the pressurized samples possess amorphous nature in many cases. We now report the high-pressure studies on a prototype AIEE-active molecule, tetraphenylethene, using diamond anvil cell technique with associated spectroscopic measurements. An unusual pressure-dependent color, intensity, and lifetime change in tetraphenylethene has been detected by steady-state photoluminescence and time-resolved emission decay measurements. The flexible role of the aromatic C-H...pi and C-H...C contacts in structural recovery, conformational modification, and emission efficiency modulation upon compression is demonstrated through structure and infrared analysis. PMID- 26278245 TI - Studying the Dynamics of Photochemical Reactions via Ultrafast Time-Resolved Infrared Spectroscopy of the Local Solvent. AB - Conventional ultrafast spectroscopic studies on the dynamics of chemical reactions in solution directly probe the solute undergoing the reaction. We provide an alternative method for probing reaction dynamics via monitoring of the surrounding solvent. When the reaction exchanges the energy (in form of heat) with the solvent, the absorption cross sections of the solvent's infrared bands are sensitive to the heat transfer, allowing spectral tracking of the reaction dynamics. This spectroscopic technique was demonstrated to be able to distinguish the differing photoisomerization dynamics of the trans and cis isomers of stilbene in acetonitrile solution. We highlight the potential of this spectroscopic approach for studying the dynamics of chemical reactions or other heat transfer processes when probing the solvent is more experimentally feasible than probing the solute directly. PMID- 26278246 TI - Nanomembrane Containing a Nanopore in an Electrolyte Solution: A Molecular Dynamics Approach. AB - Molecular dynamics simulation is used to acquire information about the characteristics of a nanographene membrane immersed in an electrolyte solution of KCl and subjected to an electric field. The membrane possesses one nanopore. It is shown that the solution contains in addition to hydrated ions, hydrated ion pairs, and hydrated clusters with more than two ions. The fractions of hydrated ions, hydrated ion pairs and hydrated clusters as well as their hydration numbers were also calculated. It was found that the hydration numbers remain constant at low electric fields but decrease at high electric fields. Under the action of an electric field, the K(+) and Cl(-) ions separate on the two sides of graphene, thus generating hydrated ion polarization layers, which result in negative charge density layers and positive ones on the left and right interfaces of the water/graphene. Thus, the neutral graphene becomes asymmetrically charged. PMID- 26278247 TI - Control Mechanism of Excitation Energy Transfer in a Complex Consisting of Photosystem II and Fucoxanthin Chlorophyll a/c-Binding Protein. AB - Fucoxanthin chlorophyll (Chl) a/c-binding protein (FCP) is a unique light harvesting antenna in diatoms, which are photosynthesizing algae ubiquitous in aquatic environments. However, it is unknown how excitation energy is trapped and quenched in a complex consisting of photosystem II and FCP (PSII-FCPII complex). Here, we report the control mechanism of excitation energy transfer in the PSII FCPII complexes isolated from a diatom, Chaetoceros gracilis, as revealed by picosecond time-resolved fluorescence spectroscopy. The results showed that Chl excitation energy is harvested in low-energy Chls near/within FCPII under the 77 K conditions, whereas most of the energy is trapped in reaction center Chls in PSII under the 283 K conditions. Surprisingly, excitation energy quenching was observed in a part of PSII-FCPII complexes with the time constants of hundreds of picosecond, thus indicating the large contribution of FCPII to energy trapping and quenching. On the basis of these results, we discuss the light-harvesting strategy of diatoms. PMID- 26278248 TI - Dynamics of Dielectrophoretic-Force-Directed Assembly of NaYF4 Colloidal Nanocrystals into Tunable Multilayered Micropatterns. AB - The dynamics of dielectrophoretic-force-directed assembly of polarizable colloidal upconverting beta-NaYF4 nanocrystals into tunable multilayers on charge micropatterns written by atomic force microscopy is investigated. Multilayered nanocrystal assembly by this nanoxerography process occurs in two phases. During the first phase typically lasting a few minutes, the nanocrystal assemblies grow up to a maximum thickness under the influence of strong dielectrophoretic forces exerted by the charge patterns. Subsequently, the nanocrystals start to diffuse back into the solvent, leaving a single layer attached to the charge patterns. A theoretical model based on the Fokker-Planck equation is formulated to describe this dynamics involving an interplay of diffusive and dielectrophoretic forces. Being in good agreement with the experimental results, this approach may be reliably extended to simulate the directed assembly of other types of polarizable colloids from liquid phase by nanoxerography. PMID- 26278249 TI - Preparation of Bi-Based Ternary Oxide Photoanodes BiVO4, Bi2WO6, and Bi2Mo3O12 Using Dendritic Bi Metal Electrodes. AB - The major limitation to investigating a variety of ternary oxides for use in solar energy conversion is the lack of synthesis methods to prepare them as high quality electrodes. In this study, we demonstrate that Bi-based n-type ternary oxides, BiVO4, Bi2WO6, and Bi2Mo3O12, can be prepared as high-quality polycrystalline electrodes by mild chemical and thermal treatments of electrodeposited dendritic Bi films. The resulting oxide films have good coverage, adhesion, and electrical continuity, allowing for facile and accurate evaluation of these compounds for use in solar water oxidation. In particular, the BiVO4 electrode retained the porosity and nanocrystallinity of the original dendritic Bi film. This feature increased the electron-hole separation yield, making this compound more favorable for use as a photoanode in a photoelectrochemical cell. PMID- 26278250 TI - Probing, Sensing, and Fluorescence Enhancement with Single Gold Nanorods. AB - Gold nanorods with dimensions around 10-100 nm present original optical properties. Their main advantages are the tunability from 600 to 1000 nm of their main absorption band, and its high intensity, stemming from the good conducting properties of gold in this spectral range. Gold nanorods have been applied to tracking, probing, sensing, and manipulation experiments. Here, we discuss experiments done with single gold nanorods with emphasis on recent results from our group. PMID- 26278251 TI - Surface Plasmons as Versatile Analytical Tools. PMID- 26278252 TI - Resonance Raman Analysis of the Tryptophan Cation Radical. AB - Electron transfer (ET) reactions within proteins are accomplished by a broad set of redox-active molecules, including natural amino acids. Tryptophan participates in ET chemistry as both a cation and a neutral radical. Identification and characterization of the biologically relevant species is essential to understand efficient ET mechanisms in proteins. We present resonance Raman spectra and excitation profiles of the tryptophan cation radical generated by combining a strong oxidant, Ce(IV), with tryptophan model compounds in a fast-flow mixing device. Isotopically modified derivatives, coupled with calculations, allowed the assignment of the normal modes of this radical. Raman bands that are sensitive to protonation state and hydrogen bonding environment of the cation radical were identified. The present findings, along with resonance Raman spectra of the closed-shell and neutral radical counterparts, form a foundation for probing tryptophan-mediated ET reactions in proteins. PMID- 26278253 TI - Molecular Theory for Electrokinetic Transport in pH-Regulated Nanochannels. AB - Ion transport through nanochannels depends on various external driving forces as well as the structural and hydrodynamic inhomogeneity of the confined fluid inside of the pore. Conventional models of electrokinetic transport neglect the discrete nature of ionic species and electrostatic correlations important at the boundary and often lead to inconsistent predictions of the surface potential and the surface charge density. Here, we demonstrate that the electrokinetic phenomena can be successfully described by the classical density functional theory in conjunction with the Navier-Stokes equation for the fluid flow. The new theoretical procedure predicts ion conductivity in various pH-regulated nanochannels under different driving forces, in excellent agreement with experimental data. PMID- 26278254 TI - Extraction of Cations from an Ionic Liquid Droplet in a Dielectric Liquid under Electric Field. AB - Ionic liquids show great promise as excellent solvents or catalysts in energy and biological fields due to their unique chemical and physical properties. In this work, the characteristics of various ionic liquids are investigated with the electrophoresis of a charged droplet (ECD) method. Under normal situation, a charged droplet in a dielectric liquid shows back-and-forth bouncing motion between the positive and negative electrodes continuously. However, for some special ionic liquids, interesting retreating behavior of a charged droplet has been observed. This retreating behavior is due to the loss of positive charges of the droplet, and it suggests that only the positive ions are extracted from the droplet under the applied electric field. Based on this hypothesis of ion extraction, Fourier transform infrared (FTIR) spectroscopy analysis has been performed. The retreating behavior is also discussed from the intermolecular point of view according to the ion species. PMID- 26278255 TI - Uncovering Hot Hole Dynamics in CdSe Nanocrystals. AB - Single and multiple exciton relaxation dynamics of CdSe/CdZnS nanocrystal quantum dots (QDs) monitored at the two lowest optical transitions, 1Se-1S3/2 and 1Se 2S3/2, have been examined using ultrafast transient absorption (TA) spectroscopy. For the CdSe/CdZnS QDs studied, the 1Se-1S3/2 and 1Se-2S3/2 transitions are widely separated (~180 meV) compared to bare CdSe QDs (~50-100 meV), allowing for clearly distinguishable TA signals attributable to hot hole relaxation. Holes depopulate from the 2S3/2 state with a lifetime of 7 +/- 2 ps, which is consistent with the predictions for hole relaxation via a phonon coupling pathway to lower-energy hole states, with possible contributions from hole trapping as well. These results suggest that tuning the surface chemistry of semiconductor QDs is a viable route to measure and possibly control their hot hole relaxation dynamics. PMID- 26278256 TI - Persistent Subdiffusive Proton Transport in Perfluorosulfonic Acid Membranes. AB - Proton transport (PT) in solutions of small amphiphiles in water has previously been shown to be subdiffusive for long times. The present study analyzes simulations of hydrated perfluorosulfonic acid (PFSA) membranes in order to determine whether PT is also subdiffusive in these important amphiphilic systems. We show that PT is indeed subdiffusive for several hundred picoseconds for all hydration levels examined, and the subdiffusive behavior is highly dependent on water concentration. We also investigate the caging of the excess proton using a recently developed technique and show that the excess proton exhibits caging effects up to at least 1 ns in PFSA systems. In order to fully characterize the long-time behavior of PT in PFSAs, these results demonstrate that multiple nanosecond trajectories are needed, well beyond the current capabilities of ab initio molecular dynamics. PMID- 26278257 TI - alpha-Casein Inhibits Insulin Amyloid Formation by Preventing the Onset of Secondary Nucleation Processes. AB - alpha-Casein is known to inhibit the aggregation of several proteins, including the amyloid beta-peptide, by mechanisms that are not yet completely clear. We studied its effects on insulin, a system extensively used to investigate the properties of amyloids, many of which are common to all proteins and peptides. In particular, as for other proteins, insulin aggregation is affected by secondary nucleation pathways. We found that alpha-casein strongly delays insulin amyloid formation, even at extremely low doses, when the aggregation process is characterized by secondary nucleation. At difference, it has a vanishing inhibitory effect on the initial oligomer formation, which is observed at high concentration and does not involve any secondary nucleation pathway. These results indicate that an efficient inhibition of amyloid formation can be achieved by chaperone-like systems, by sequestering the early aggregates, before they can trigger the exponential proliferation brought about by secondary nucleation mechanisms. PMID- 26278258 TI - Isotope-Dependent Rotational States Distributions Enhanced by Dynamic Resonance States: A Comparison Study of the F + HD -> HF(vHF = 2) + D and F + H2 -> HF(vHF = 2) + H Reaction. AB - An interesting trimodal structure in the HF (v' = 2) rotational distribution produced by the F + HD (v = 0, j = 0) reaction, but monomodal structure in the HF (v' = 2) rotational distribution produced by the F + H2 (v = 0, j = 0) reaction, were observed using a high-resolution crossed molecular beam apparatus. The rotational states of product HF (v' = 2) are much hotter in the F + HD reaction. It is uncovered that the observations are due to the dominant role of the dynamical resonance states in these two isotopic reactions. The angular potential well in the region of the resonance state of the F + HD reaction is much deeper and supports wave function with high angular kinetic energy, which in turn comes from different H tunneling processes in the F + HD and F + H2 reaction. PMID- 26278259 TI - Rapid and Accurate Machine Learning Recognition of High Performing Metal Organic Frameworks for CO2 Capture. AB - In this work, we have developed quantitative structure-property relationship (QSPR) models using advanced machine learning algorithms that can rapidly and accurately recognize high-performing metal organic framework (MOF) materials for CO2 capture. More specifically, QSPR classifiers have been developed that can, in a fraction of a section, identify candidate MOFs with enhanced CO2 adsorption capacity (>1 mmol/g at 0.15 bar and >4 mmol/g at 1 bar). The models were tested on a large set of 292 050 MOFs that were not part of the training set. The QSPR classifier could recover 945 of the top 1000 MOFs in the test set while flagging only 10% of the whole library for compute intensive screening. Thus, using the machine learning classifiers as part of a high-throughput screening protocol would result in an order of magnitude reduction in compute time and allow intractably large structure libraries and search spaces to be screened. PMID- 26278260 TI - Computed and Experimental Absorption Spectra of the Perovskite CH3NH3PbI3. AB - Electronic structure and light absorption properties of the perovskite CH3NH3PbI3 are investigated by relativistic density functional theory with quasiparticle GW corrections and many-body interactions. The nature of the Wannier exciton is studied by solving the Bethe-Salpeter equation augmented with the analysis of a conceptual hydrogen-like model. The computed absorption spectrum unravels a remarkable absorption "gap" between the first two absorption peaks. This discontinuity is maintained in the calculated tetragonal structure that, however, is not stable at low temperature. Most importantly, the discontinuity is also observed in the experimental absorption spectrum of the orthorhombic single crystal at low temperature (4 K). However, in contrast to the single crystal, in a polycrystalline perovskite film at 5 K the "gap" is filled by a monotonously increasing absorption throughout the visible range. This feature of thin films points to the potential significance of defect absorption for the excellent light harvesting properties of perovskite-based solar cells. PMID- 26278261 TI - Correction to "Bulk Liquid Water at Ambient Temperature and Pressure from MP2 Theory". PMID- 26278262 TI - Host-Guest Interactions in Dealuminated HY Zeolite Probed by (13)C-(27)Al Solid State NMR Spectroscopy. AB - Host-guest interactions in dealuminated HY zeolite have been investigated by advanced (13)C-(27)Al solid-state NMR experiments. This analysis allows us to report new insights into the adsorption geometry of acetone and its interaction with acid sites in the zeolite channels. PMID- 26278263 TI - Femtosecond Trapping of Free Electrons in Ultrathin Films of NaCl on Ag(100). AB - We report the excited-state electron dynamics for ultrathin films of NaCl on Ag(100). The first three image potential states (IPSs) were initially observed following excitation. The electrons in the spatially delocalized n = 1 IPS decayed on the ultrafast time scale into multiple spatially localized states lower in energy. The localized electronic states are proposed to correspond to electrons trapped at defects in the NaCl islands. Coverage and temperature dependence of the localized states support the assignment to surface trap states existing at the NaCl/vacuum interface. These results highlight the importance of electron trapping in ultrathin insulating layers. PMID- 26278264 TI - Complex Absorbing Potential Equation-of-Motion Coupled-Cluster Method Yields Smooth and Internally Consistent Potential Energy Surfaces and Lifetimes for Molecular Resonances. PMID- 26278265 TI - The Reaction Mechanism and Capacity Degradation Model in Lithium Insertion Organic Cathodes, Li2C6O6, Using Combined Experimental and First Principle Studies. AB - Herein, we explore the capacity degradation of dilithium rhodizonate salt (Li2C6O6) in lithium rechargeable batteries based on detailed investigations of the lithium de/insertion mechanism in Li2C6O6 using both electrochemical and structural ex situ analyses combined with first-principles calculations. The experimental observations indicate that the LixC6O6 electrode undergoes multiple two-phase reactions in the composition range of 2 <= x <= 6; however, the transformations in the range 2 <= x <= 4 involve a major morphological change that eventually leads to particle exfoliation and the isolation of active material. Through first-principles analysis of LixC6O6 during de/lithiation, it was revealed that particle exfoliation is closely related to the crystal structural changes with lithium deinsertion from C6O6 interlayers of the LixC6O6. Among the lithium ions found at various sites, the extraction of lithium from C6O6 interlayers at 2 <= x <= 4 decreases the binding force between the C6O6 layers, promoting the exfoliation of C6O6 layers and pulverization at the electrode, which degrades capacity retention. PMID- 26278266 TI - Immunohistochemical study of RhoC GTPase in oral squamous cell carcinoma. AB - Oral squamous cell carcinoma (OSCC) is a disease with high mortality and morbidity. Metastasis is a significant prognostic factor of the OSCC patients. The Rho GTPases are signaling proteins that controls important cellular processes in various complex mechanisms involved in carcinogenesis. This study aimed to evaluate the expression pattern of RhoC in OSCC protein by immunohistochemistry in situ. Immunohistochemical reactions were performed for RhoC by the method of avitina-biotin-peroxidase activity in samples OSCC: well differentiated (BD, n=6), moderately differentiated (MD, n=24) and poorly differentiated (PD, n=13). The morphometry was taken by QuickScore (percentage and intensity of staining) and only intensity staining. There was no statistical difference (p>0.05) through none of the modes of morphometric analysis between BD, MD and PD. And the RhoC staining was not associated with the histopathologic grading (chi2 = 4.65, p>0.05). However, the morphological evaluation of immunostained for RhoC in cases BD, MD, PD OSCC, regardless of histopathologic grading. These results suggest that there is no correlation between the RhoC immunoexpression and histopathological grading of OSCC. PMID- 26278267 TI - Radioprotective effect of chicory seeds against genotoxicity induced by ionizing radiation in human normal lymphocytes. AB - The search for less-toxic radioprotective agents has led to a growing trend towards natural products. Protective effect of the methanolic extract of chicory seeds (MCS) was investigated against genotoxicity induced by ionizing radiation in human lymphocytes. Human peripheral blood samples were collected and incubated with MCS at different concentrations (10, 50, 100, and 200 MUg/mL) for two hours. The whole blood samples were exposed in vitro to X-ray at dose 2.5 Gy. Then, the lymphocytes were cultured with mitogenic stimulation to determine the micronucleus in cytokinesis blocked binucleated cell. The methanolic extract at all doses significantly reduced the frequency of micronuclei in binucleated lymphocytes, as compared with similarly irradiated lymphocytes without any extract treatment. The maximum protection was observed at 200 MUg/mL of MCS, it completely protected genotoxicity induced by ionizing radiation in human lymphocytes. The extract exhibited a concentration-dependent radical scavenging activity on 1,1-diphenyl-2-picryl hydrazyl free radicals. HPLC analysis of MCS showed this extract is containing chlorogenic acid as a phenolic compound. These data suggest that the radioprotective effect of methanolic extract of chicory seeds can be attributed to the presence of phenolic compounds such as chlorogenic acid which act as antioxidant agents. PMID- 26278268 TI - Mutation analysis of the CYP21A2 gene in congenital adrenal hyperplasia. AB - Congenital adrenal hyperplasia (CAH) is an inherited autosomal recessive enzymatic disorder involving the synthesis of adrenal corticosteroids. 21 Hydroxylase deficiency (21-OHD) is the most common form of the disease which is observed in more than 90% of patients with CAH. Early identification of mutations in the genes involved in this disease is critical. A marker of the disease, errors in the CYP21A2 gene, is thought to be part of the pathophysiology of CAH. Therefore, the identification of gene mutations would be very beneficial in the early detection of CAH. This research was a descriptive epidemiological study conducted on individuals elected by the inclusion criteria whom were referred to the Genetic Diagnosis Center of Tabriz during 2012 to 2013. After sampling and DNA extraction, PCR for the detection of mutations in the CYP21A2 gene was performed followed by sequencing. For data analysis, the results of sequencing were compared with the reference gene by blast, Gene Runner and MEGA-5 software. Obtained changes were compared with NCBI databases. The analysis of the sequencing determined the mutations located in Exons 6, 7, 8 and 10. The most frequent findings were Q318X (53%) and R356W (28%). Exon 6 cluster (7%), E431k (4%), V237E (2%), V281L (2%), E351K (2%), R426C (2%) were also frequent in our patients. The most frequent genotype was compound heterozygote, Q318X/R356W. Three rare mutations in our study were E431K, E351K and R426C. Observed mutation frequencies in this study were much higher than those reported in previous studies in Iranian populations. Thus, it seems that it is necessary to follow-up screening programs and use sequencing methods to better identify mutations in the development of the disease. PMID- 26278269 TI - Housestaff Knowledge Related to Urinary Catheter Use and Catheter-Associated Urinary Tract Infections. AB - Despite published catheter-associated urinary tract infection prevention guidelines, inappropriate catheter use is common. We surveyed housestaff about their knowledge of catheter-associated urinary tract infections at a teaching hospital and found most are aware of prevention guidelines; however, their application to clinical scenarios and catheter practices fall short of national goals. PMID- 26278271 TI - Editorial: Novel Inflammatory Biomarkers in Cardiovascular Disease: From Molecular Mechanisms to Therapeutic Targets (Part-II). PMID- 26278270 TI - Total Convection Affects Serum beta2 Microglobulin and C-Reactive Protein but Not Erythropoietin Requirement following Post-Dilutional Hemodiafiltration. AB - BACKGROUND: Inflammation and increased erythropoiesis stimulating agents (ESA) requirement are frequently associated in patients on dialysis. On-line hemodiafiltration (ol-HDF), putting together high levels of diffusion, and convection could improve both conditions. However, it is still not known which depurative component plays a major role in determining this result. The aim of the study was to evaluate the role of convection and diffusion on long-term variations of serum beta2 microglobulin (Deltabeta2M), high-sensitive C-reactive protein (DeltahsCRP) concentrations, and ESA requirement (DeltaESA) in ol-HDF. METHODS: Seventy-three patients prevalent on high flux HD (hfHD) were studied. Thirty-eight patients were switched from hfHD to post-dilutional ol-HDF (Study group); the other 35 patients were considered the Control group. At 6 and 12 months, the effects of ol-HDF and hfHD on DeltahsCRP, DeltaB2M, and DeltaESA (U/kg/week) were evaluated. Other variables considered were body weight (BW), serum albumin (sAlb), hemoglobin (Hb), and equilibrated Kt/V (eKt/V). Iron therapy and ESA were administered intravenously according to the K/DOQI guidelines in order to maintain transferrin saturation between 20 and 40%, serum ferritin between 150 and 500 ng/ml and Hb between 11 and 12 g/dl. Qb, treatment time and Qd remained constant. Ol-HDF and hfHD were performed using membranes of size 1.9-2.1 sqm. Ultrapure dialysate and substitution fluid were employed in both HDF and HD treatments. Data are expressed as mean +/- SD. Paired t test, Mann-Whitney U test, and simple and multiple regression analyses were employed for statistical evaluation. RESULTS: STUDY GROUP: total convective volume (TCV) was 22.1 +/- 1.9 l/session. A significant reduction of hsCRP: from 6.8 +/- 7.1 to 2.3 +/- 2.4 mg/dl (p < 0.001), beta2M: from 36.5 +/- 14.4 to 24.7 +/- 8.6 mg/dl (p < 0.0001) and ESAdose: from 107 +/- 67 to 65 +/- 44 U/kg/week (p < 0.005) was observed. No significant variations of Hb, BW and sAlb were seen. A significant inverse correlation was found between TCV and Deltabeta2M (r = -0.627; p < 0.0001), and TCV and DeltahsCRP (r = -0.514; p < 0.0001); no correlation between TCV and DeltaESAdose was observed. No correlation was found between eKt/V and Deltabeta2M, DeltahsCRP, and DeltaESAdose. Multiple regression analysis with DeltaESAdose as dependent variable showed DeltahsCRP as the only significantly associated independent factor (p < 0.01). CONTROL GROUP: no significant variations of hsCRP, beta2M, and ESAdose were observed over time. CONCLUSIONS: Ol HDF induces a long-term significant reduction in pre-dialysis beta2M and hsCRP concentrations. The magnitude of reduction is directly correlated to the amount of TCV achieved but not on eKt/V. The observed reduction in ESAdose requirement is independent either on convection or diffusion, but is directly associated to the concomitant reduction of inflammation. PMID- 26278272 TI - Gender-Related Differences in Patients Presenting with Suspected Acute Coronary Syndromes: Clinical Presentation, Biomarkers and Diagnosis. AB - OBJECTIVES: Gender differences in patients presenting with suspected acute coronary syndromes (ACS) have not yet been fully characterized. The aim of this study was to assess gender-related disparities in clinical profiles, biomarkers and diagnoses of patients with suspected ACS. METHODS: This single-centre, prospective cohort study included 377 consecutive patients presenting with suspected ACS to the emergency department. Suspected ACS was defined as a request for conventional troponin T (c-cTnT) measurements on clinical grounds. RESULTS: Women were older than men (p = 0.004), and had a lower prevalence of known coronary artery and peripheral vascular disease (p < 0.05). c-cTnT was positive in 8% of female and in 14% of male patients (p = 0.16), TIMI risk score and cardiac biomarkers including c-cTnT, hs-cTnT, myoglobin, creatine kinase, N terminal pro-brain natriuretic peptide, myeloid-related protein 8/14 and pregnancy-associated plasma protein A were lower in women (p < 0.05). Women were less frequently diagnosed with ACS (30 vs. 51%), and were not referred for urgent coronary angiography as often as men (p < 0.001). In multivariate analysis, female gender was associated with a lower referral for coronary angiography (HR 0.41, 95% CI 0.23-0.78, p = 0.006). CONCLUSIONS: In patients with suspected ACS, women presented with different biomarker profiles, and were less often diagnosed with ACS and referred to coronary angiography. PMID- 26278273 TI - Sluggish Cognitive Tempo and ADHD Inattention as Predictors of Externalizing, Internalizing, and Impairment Domains: A 2-Year Longitudinal Study. AB - Although sluggish cognitive tempo (SCT) is distinct from attention deficit/hyperactivity disorder inattention (ADHD-IN), few studies have examined whether SCT longitudinally predicts other symptom or impairment dimensions. This study used 4 sources (mothers, fathers, primary teachers, and secondary teachers) and 3 occasions of measurement (first, second, and third grades) with 758 first grade (55 % boys), 718 second grade (54 % boys), and 585 third grade (53 % boys) children from Spain to determine SCT's and ADHD-IN's unique longitudinal relationships with psychopathology, academic impairment, and social impairment over the 1- and 2-year intervals (i.e., first to third grade, second to third grade). For 1- and 2-year intervals using both mothers' and fathers' ratings, higher levels of SCT uniquely predicted higher levels of anxiety, depression, academic impairment, and social impairment whereas higher levels of ADHD-IN uniquely predicted higher levels of ADHD-HI, ODD, and academic impairment. For 1- and 2-year intervals across different primary and secondary teachers (i.e., first/second and third grade ratings were provided by different teachers), higher scores on ADHD-IN uniquely predicted poorer outcomes across domains whereas higher scores on SCT uniquely predicted lower levels of ADHD-HI and ODD for both intervals in addition to higher levels of depression (for primary teachers only), academic impairment (for 1-year interval only), and peer rejection (2-year interval only for primary teachers). Overall, SCT was significantly associated with important outcomes independent of ADHD-IN over 1- and 2-year intervals and across four different raters. This study provides further evidence for distinguishing between SCT and ADHD-IN in home and school settings. PMID- 26278274 TI - On the relation between self-reported cognitive fatigue and the posterior hypothalamic-brainstem network. AB - BACKGROUND AND PURPOSE: Various causes have been suggested for multiple sclerosis (MS) related fatigue. Hypothalamus-brainstem fibres play a role in sleep-wake regulation and in hypothalamic deactivation during inflammatory states. Hence, they may play a role for experiencing fatigue by changing bottom-up hypothalamic activation. METHODS: Multiple sclerosis patients with and without self-reported cognitive fatigue and healthy controls were analysed with respect to the integrity of hypothalamus-brainstem fibres using diffusion-tensor imaging based tractography, focusing on the anterior, medial and posterior hypothalamic areas, controlling for clinical impairment and excluding participants with depressive mood. RESULTS: Multiple sclerosis patients without self-reported cognitive fatigue showed increased axial and radial diffusivity levels specifically for fibres connecting the right posterior hypothalamus with the right locus coeruleus, but not for the medial hypothalamus and the corpus callosum. Moreover, there were no differences between MS patients with and without fatigue in brain atrophy and lesion load, which could explain our results. CONCLUSION: Multiple sclerosis patients not experiencing fatigue show increased axial and radial diffusivity for fibres connecting the posterior hypothalamus and the brainstem, which might prevent bottom-up activation of the posterior hypothalamus and therefore downregulation of structures responsible for wakefulness and exploratory states of mind. PMID- 26278275 TI - A nonparametric fiducial interval for the Youden index in multi-state diagnostic settings. AB - The Youden index is a commonly employed metric to characterize the performance of a diagnostic test at its optimal point. For tests with three or more outcome classes, the Youden index has been extended; however, there are limited methods to compute a confidence interval (CI) about its value. Often, outcome classes are assumed to be normally distributed, which facilitates computational formulas for the CI bounds; however, many scenarios exist for which these assumptions cannot be made. In addition, many of these existing CI methods do not work well for small sample sizes. We propose a method to compute a nonparametric interval about the Youden index utilizing the fiducial argument. This fiducial interval ensures that CI coverage is met regardless of sample size, underlying distributional assumptions, or use of a complex classifier for diagnosis. Two alternate fiducial intervals are also considered. A simulation was conducted, which demonstrates the coverage and interval length for the proposed methods. Comparisons were made using no distributional assumptions on the outcome classes and for when outcomes were assumed to be normally distributed. In general, coverage probability was consistently met, and interval length was reasonable. The proposed fiducial method was also demonstrated in data examining biomarkers in subjects to predict diagnostic stages ranging from normal kidney function to chronic allograph nephropathy. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. PMID- 26278276 TI - Increase in pulmonary blood flow at birth: role of oxygen and lung aeration. AB - Lung aeration stimulates the increase in pulmonary blood flow (PBF) at birth, but the spatial relationships between PBF and lung aeration and the role of increased oxygenation remain unclear. Using simultaneous phase-contrast X-ray imaging and angiography, we have investigated the separate roles of lung aeration and increased oxygenation in PBF changes at birth using near-term (30 days of gestation) rabbit kits (n = 18). Rabbits were imaged before ventilation, then the right lung was ventilated with 100% nitrogen (N2), air or 100% O2 (oxygen), before all kits were switched to ventilation in air, followed by ventilation of both lungs using air. Unilateral ventilation of the right lung with 100% N2 significantly increased heart rate (from 69.4 +/- 4.9 to 93.0 +/- 15.0 bpm), the diameters of both left and right pulmonary axial arteries, number of visible vessels in both left and right lungs, relative PBF index in both pulmonary arteries, and reduced bolus transit time for both left and right axial arteries (from 1.34 +/- 0.39 and 1.81 +/- 0.43 s to 0.52 +/- 0.17 and 0.89 +/- 0.21 s in the left and right axial arteries, respectively). Similar changes were observed with 100% oxygen, but increases in visible vessel number and vessel diameter of the axial arteries were greater in the ventilated right lung during unilateral ventilation. These findings confirm that PBF increase at birth is not spatially related to lung aeration and that the increase in PBF to unventilated regions is unrelated to oxygenation, although oxygen can potentiate this increase. PMID- 26278278 TI - Quantitative Detection of Photothermal and Photoelectrocatalytic Effects Induced by SPR from Au@Pt Nanoparticles. AB - The surface plasmon resonance (SPR) induced photothermal and photoelectrocatalysis effects are crucial for catalytic reactions in many areas. However, it is still difficult to distinguish these two effects quantitatively. Here we used surface-enhanced Raman scattering (SERS) to detect the photothermal and photoelectrocatalytic effects induced by SPR from Au core Pt shell Nanoparticles (Au@Pt NPs), and calculated the quantitative contribution of the ratio of the photothermal and photoelectrocatalysis effects towards the catalytic activity. The photothermal effect on the nanoparticle surface after illumination is detected by SERS. The photoelectrocatalytic effect generated from SPR is proved by SERS with a probe molecule of p-aminothiophenol (PATP). PMID- 26278277 TI - Sensitive periods for 17beta-estradiol exposure during immune system development in sea bass head kidney. AB - An increasing body of evidence suggests that sex steroids play an important role in the development and regulation of vertebrate immune defense. Therefore, compounds with estrogenic activity may influence the immune system via receptor mediated pathways. The presence of estrogen receptors in immune cells and organs during the early stages of development may indicate that female steroid hormones are involved in the maturation of the fish immune system. This is of particular importance, as some marine fish are probably exposed to sources of exogenous estrogens while they reside in their estuarine nursery grounds. In this study, the influence of 17beta-estradiol (E2) on estrogen receptor and cytokine gene expression was assessed in juvenile sea bass (Dicentrarchus labrax) together with characterization of the head kidney leukocyte populations and corresponding phagocytic activity during organ regionalization from 98 to 239 dph. E2 exposure, beginning at 90 dph resulted in indirect and delayed modifications of interleukin 1beta and estrogen receptor alpha gene expression, which may affect B-lymphocyte proliferation in the sea bass head kidney. The E2 treatment of 120 dph fish led to an increase in estrogen receptor beta2 and a decrease in transforming growth factor beta1 gene expression, which coincided with decreased phagocytic activity of head kidney lymphocytes and monocytes/macrophages. Additionally, these changes were observed during developmental periods described as critical phases for B lymphocyte development in mammals. Consequently, exogenous estrogens have the potential to modify the innate immune response in juvenile sea bass and to exert detrimental effects on head kidney development. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26278279 TI - Editorial Comment to Impact of smoking on the age at diagnosis of upper tract urothelial carcinoma: Subanalysis of the Japanese Urological Association multi institutional national database. PMID- 26278281 TI - Regulation of GAPDH expression by treatment with the beta-adrenoceptor agonist isoprenaline--is GADPH a suitable loading control in immunoblot experiments? PMID- 26278280 TI - Macronutrient and micronutrient intakes of children in Oklahoma child-care centres, USA. AB - OBJECTIVE: To determine macronutrients and micronutrients in foods served to and consumed by children at child-care centres in Oklahoma, USA and compare them with Dietary Reference Intakes (DRI). DESIGN: Observed lunch nutrients compared with one-third of the age-based DRI (for 1-3 years-olds and 4-8-year-olds). Settings Oklahoma child-care centres (n 25), USA. SUBJECTS: Children aged 3-5 years (n 415). RESULTS: Regarding macronutrients, children were served 1782 (sd 686) kJ (426 (sd 164) kcal), 22.0 (sd 9.0) g protein, 51.5 (sd 20.4) g carbohydrate and 30.7 (sd 8.7) % total fat; they consumed 1305 (sd 669) kJ (312 (sd 160 kcal), 16.0 (sd 9.1) g protein, 37.6 (sd 18.5) g carbohydrate and 28.9 (sd 10.6) % total fat. For both age-based DRI: served energy (22-33 % of children), protein and carbohydrate exceeded; consumed energy (7-13 % of children) and protein exceeded, while carbohydrate was inadequate. Regarding micronutrients, for both age-based DRI: served Mg (65.9 (sd 24.7) mg), Zn (3.8 (sd 11.8) mg), vitamin A (249.9 (sd 228.3) MUg) and folate (71.9 (sd 40.1) ug) exceeded; vitamin E (1.4 (sd 2.1) mg) was inadequate; served Fe (2.8 (sd 1.8) mg) exceeded only in 1-3-year-olds. Consumed folate (48.3 (sd 38.4) ug) met; Ca (259.4 (sd 146.2) mg) and Zn (2.3 (sd 3.0) mg) exceeded for 1-3-year-olds, but were inadequate for 4-8-year-olds. For both age-based DRI: consumed Fe (1.9 (sd 1.2) mg) and vitamin E (1.0 (sd 1.7) mg) were inadequate; Mg (47.2 (sd 21.8) mg) and vitamin A (155.0 (sd 126.5) ug) exceeded. CONCLUSIONS: Lunch at child-care centres was twice the age-based DRI for consumed protein, while energy and carbohydrate were inadequate. Areas of improvement for micronutrients pertain to Fe and vitamin E for all children; Ca, Zn, vitamin E and folate for older pre-schoolers. Adequate nutrients are essential for development and the study reveals where public health nutrition experts, policy makers and care providers should focus to improve the nutrient density of foods. PMID- 26278282 TI - Aralia elata prevents neuronal death by downregulating tonicity response element binding protein in diabetic retinopathy. AB - BACKGROUND/AIMS: The present study addresses the role of tonicity response element binding protein (TonEBP) in retinal ganglion cell (RGC) death in diabetic retinopathy and the impact of Aralia elata extract on the TonEBP/RGC interaction. METHODS: Diabetes was induced in C57BL/6 mice by intraperitoneal injection of streptozotocin (STZ). Control mice received phosphate-buffered saline. After five injections of STZ or saline buffer, A. elata extract was administered by daily oral tube feeding for 7 weeks. All mice were killed at 2 months after the last injection of STZ or saline and the extent of cell death together with the protein expression levels of TonEBP, aldose reductase (AR) and nuclear factor-kappa B (NF kappaB) were examined. RESULTS: Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive signals were colocalized with TonEBP immunoreactive RGCs. The apoptotic cell death of RGCs and the expression levels of TonEBP, AR and NF-kappaB were significantly increased in the retinas of diabetic mice compared with controls at 2 months after the induction of diabetes. However, these changes were effectively blocked by the administration of A. elata extract. CONCLUSIONS: These results indicate that A. elata prevents diabetes induced RGC apoptosis and downregulates TonEBP expression. Therefore, A. elata extract may have therapeutic potential to prevent diabetes-induced retinal neurodegeneration in diabetic retinopathy. PMID- 26278283 TI - Trapped in TRAPS: Difficulty of Diagnosis due to Heterogeneity. PMID- 26278284 TI - Fever of Unknown Origin: Do Well-known Diseases Remain Undiagnosed? PMID- 26278285 TI - Association between the Postprandial Glucose Levels and Arterial Stiffness Measured According to the Cardio-ankle Vascular Index in Non-diabetic Subjects. AB - OBJECTIVE: Although a relationship between post-challenge hyperglycemia and arterial stiffness has been reported, the relationship between the postprandial glucose levels and cardio-ankle vascular index (CAVI) in non-diabetic subjects is not clear. This study thus evaluated the association between the postprandial glucose levels after a composite meal and the degree of arterial stiffness measured according to CAVI in non-diabetic subjects. METHODS: The subjects included 1,291 individuals (655 men and 636 women; mean age, 48.6 years; range, 23-85 years) who underwent medical examinations, including blood tests and CAVI assessments, between October 2005 and April 2012. The 1-hour postprandial glucose levels were determined after a 600-kcal traditional Japanese meal. RESULTS: The CAVI values were significantly higher in the subjects with higher 1-hour postprandial glucose levels (>=140 mg/dL in men; >=158 mg/dL in women). A simple regression analysis indicated that the CAVI values were significantly correlated with the 1-hour postprandial glucose levels in men (r=0.286, p<0.0001) and women (r=0.228, p<0.0001). After adjusting for age, BMI, systolic blood pressure, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, 1-hour postprandial glucose, homeostatis model assessment of insulin resistance, estimated glemerular filtration rate, and high sensitive C-reactive protein, stepwise multiple regression analysis demonstrated that the 1-hour postprandial glucose level was an independent predictor associated with the CAVI in men (p=0.003) and older women 50 years of age or older (p=0.003). CONCLUSION: This study demonstrated that the 1-hour postprandial glucose levels are associated with increased CAVI values in non-diabetic men and older women 50 years of age or older. PMID- 26278286 TI - Cross-sectional and Longitudinal Analyses of Factors Contributing to the Progressive Loss of the beta-cell Function in Type 2 Diabetes. AB - OBJECTIVE: Type 2 diabetes is a progressive disease characterized by insulin resistance and insulin secretory dysfunction. In this study, we assessed the factors contributing to an insulin secretory defect in type 2 diabetes patients. METHODS: The subjects consisted of 382 patients with type 2 diabetes, aged 57+/ 13 years. We estimated the beta-cell function using 6-min post-glucagon increments in C-peptide (DeltaCPR). RESULTS: A significant inverse correlation was observed between the time since the diagnosis of diabetes and DeltaCPR. A simple liner regression analysis showed that DeltaCPR decreases at a rate of 0.056 ng/mL/year. According to a multiple regression model, body mass index (BMI) and log (triglyceride) were positively correlated with DeltaCPR. Time since the diagnosis of diabetes, diabetes in 1st degree relatives, the presence of diabetic retinopathy, and HbA1c were inversely correlated with DeltaCPR. In 50 patients who underwent the glucagon stimulation test twice, the DeltaCPR decreased from 2.27+/-1.47 to 1.72+/-1.08 ng/mL over a period of 6.5+/-0.9 years. A multiple regression analysis revealed the BMI and fasting plasma glucose level to be significant contributing factors to the decline in DeltaCPR. CONCLUSION: The duration of diabetes, a low BMI, genetic factors, and the presence of microangiopathy may be associated with beta-cell dysfunction in diabetic patients. The observations in this study suggest that obese subjects showed a rapid decline in the beta-cell function despite an initial high CPR response. Environmental factors causing insulin resistance and glucotoxicity may therefore be involved in progressive beta-cell failure. PMID- 26278287 TI - Feasibility of Rebiopsy in Non-Small Cell Lung Cancer Treated with Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors. AB - OBJECTIVE: Analyses of tumor biopsy samples from non-small cell lung cancer patients with acquired epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) resistance are expected to reveal the molecular mechanisms of resistance. However, due to limited tissue availability, performing such analyses can be challenging. We herein investigated the feasibility of tumor rebiopsy in this patient population. METHODS: From April 2004 to March 2013, 53 consecutive patients were treated with EGFR-TKIs at our department. A retrospective medical chart review was conducted among patients with progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors criteria, as assessed radiographically. Sites of progression were evaluated at the time of PD. RESULTS: Forty patients experienced PD at the following sites: isolated central nervous system (CNS) in 10 patients; isolated bone in five patients; isolated lymph nodes in two patients; the primary lesion in 10 patients; and systemic disease in 11 patients. Concerning the site of progression, 20 of the 40 patients had a lesion that could be accessed using endobronchial, transbronchial or percutaneous biopsy procedures. Among the 19 patients with oligoprogressive disease or CNS failure, the median overall survival was 24.1 months in eight patients who had received continuing treatment with EGFR-TKIs following radiotherapy and 16.8 months in 11 patients who received other therapies after PD. CONCLUSION: In this study, few patients had a site of progression capable of being accessed using relatively noninvasive biopsy procedures. Further investigations are warranted to develop more optimal treatment strategies after PD in patients with oligoprogressive disease or CNS failure. PMID- 26278288 TI - Outcomes and Prognostic Factors in Patients with Rheumatologic Diseases Admitted to the ICU. AB - OBJECTIVE: To assess the outcomes in a large cohort of patients suffering from rheumatic diseases admitted to the ICU of a tertiary university medical center. METHODS: A retrospective chart analysis was performed in 108 patients suffering from various rheumatic diseases and the outcomes, including morbidity and mortality, were assessed in relation to the underlying diseases, treatments and complications. RESULTS: Overall, 48 patients with rheumatoid arthritis, five patients with spondyloarthritis, 14 patients with vasculitis, 30 patients with connective tissue diseases and 11 patients suffering from other rheumatologic conditions were admitted to the intensive care unit (ICU). The reasons for ICU admission included infection (30%), cardiovascular complications (22%), gastrointestinal problems (18%), endocrinological disorders (7%), neurological complications (2%) and others (3%). A total of 4% of the admitted patients required close monitoring and 14% suffered from acute exacerbation of the underlying rheumatic disease. The ICU mortality rate was 16%, whereas the overall hospital mortality rate was 20%. Fatal outcomes were related to exacerbation of the rheumatic disease in 14% of the patients, infectious complications in 46% of the patients and other reasons in 41% of the patients. An increased Apache II score, the need for mechanical ventilation, renal replacement therapy, treatment with vasopressor drugs and plasma exchange therapy were identified as risk factors for mortality. CONCLUSION: The overall outcomes of critically ill patients with rheumatic diseases are impaired compared to that observed in other patient groups. However, there were no significant differences in outcomes between the different rheumatic disease groups or based on the use of immunosuppressive therapy in this study. An increased Apache II score, the need for mechanical ventilation, renal replacement therapy, treatment with vasopressor drugs and plasma exchange therapy were identified as risk factors for mortality. PMID- 26278289 TI - Relationships between Causes of Fever of Unknown Origin and Inflammatory Markers: A Multicenter Collaborative Retrospective Study. AB - OBJECTIVE: Although inflammatory markers, such as the white blood cell (WBC) count, erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (CRP) and procalcitonin, are widely used to differentiate causes of fever of unknown origin (FUO), little is known about the usefulness of this approach. We evaluated relationships between the causes of classical FUO and the levels of inflammatory markers. METHODS: A nationwide retrospective study including 17 hospitals affiliated with the Japanese Society of Hospital General Medicine was conducted. PATIENTS: This study included 121 patients >=18 years old diagnosed with "classical FUO" (axillary temperature >=38.0 degrees C at least twice over a >=3-week period without elucidation of the cause on three outpatient visits or during three days of hospitalization) between January and December 2011. RESULTS: The causative disease was infectious diseases in 28 patients (23.1%), non infectious inflammatory disease (NIID) in 37 patients (30.6%), malignancy in 13 patients (10.7%), other in 15 patients (12.4%) and unknown in 28 patients (23.1%). The rate of malignancy was significantly higher for a WBC count of <4,000/MUL than for a WBC count of 4,000-8,000/MUL (p=0.015). Among the patients with a higher WBC count, the rate of FUO due to NIID tended to be higher and the number of unknown cases tended to be lower. All FUO patients with malignancy showed an ESR of >40 mm/h. A normal ESR appeared to constitute powerful evidence for excluding a diagnosis of malignancy. In contrast, the concentrations of both serum CRP and procalcitonin appeared to be unrelated to the causative disease. CONCLUSION: The present study identified inflammatory markers that should be considered in the differential diagnosis of classical FUO, providing useful information for future diagnosis. PMID- 26278290 TI - Multiple Colon Ulcers with Typical Small Intestinal Lesions Induced by Non Steroidal Anti-Inflammatory Drugs. AB - The diagnosis of NSAID-induced colon ulcers is difficult when the distribution or endoscopic findings are not typical. An 83-year-old woman was transferred to our hospital for hemorrhagic diarrhea. Colonoscopy showed multiple ulcers in the entire colon, particularly longitudinal ulcers in the transverse colon. These were unusual for NSAID-induced colopathy, although she had been on meloxicam. However, capsule endoscopy revealed multiple scars and erosions, characteristic of NSAIDs users. The final diagnosis was NSAID-induced enteropathy, and all lesions were in remission after meloxicam discontinuation. We herein emphasize the value of an endoscopic assessment of the entire digestive tract in the diagnosis of NSAID-induced mucosal lesions. PMID- 26278291 TI - Hepatic Intracystic Organizing Hematoma Mimicking Biliary Cystadenocarcinoma in a Patient with Polycystic Liver Disease. AB - Hepatic intracystic hemorrhage is a rare complication of polycystic liver diseases, such as autosomal dominant polycystic kidney disease (ADPKD). A hepatic cyst with mural nodules and septation may suggest the presence of a cystic malignancy, such as biliary cystadenocarcinoma. We herein report a case of hepatic intracystic hematoma with a mural nodule mimicking biliary cystadenocarcinoma in a patient with ADPKD. Hepatic intracystic hemorrhage with a mural nodule is a very rare occurrence. A fat-saturated T1-weighted magnetic resonance image may be useful for making an accurate diagnosis of intracystic hematoma. PMID- 26278292 TI - A Patient with Pancreatic Castleman's Disease Arising around the Main Pancreatic Duct. AB - Castleman's disease of the pancreas is extremely rare. To the best of our knowledge, Castleman's disease arising around the main pancreatic duct has not been previously reported. The patient was a 74-year-old man. Abdominal ultrasonography performed at a health check-up revealed a dilated main pancreatic duct. Pancreatic cancer was strongly suspected on various imaging studies. However, the results of a cytological examination of the pancreatic juice were negative for malignancy. The patient did not want to undergo a histological diagnosis by endoscopic ultrasound-guided fine-needle aspiration, thus pylorus preserving pancreatoduodenectomy was performed. Pancreatic Castleman's disease arising around the main pancreatic was diagnosed by the histopathological examination. PMID- 26278293 TI - Association of Primary Biliary Cirrhosis-autoimmune Hepatitis Overlap Syndrome with Immune Thrombocytopenia and Graves' Disease. AB - A 54-year-old woman suffering from pruritus for five years was diagnosed to have Graves' disease and immune thrombocytopenia (ITP) associated with primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome, which was confirmed histologically after a prompt recovery in the platelet count number following steroid therapy. The association between PBC-AIH overlap syndrome and ITP has been rarely reported and the additional association with Graves' disease has not yet been reported. An underlying global derangement of autoimmunity or shared genetic susceptibility was suspected. PMID- 26278294 TI - Takotsubo Cardiomyopathy Triggered by Influenza A Virus. AB - We herein report the first case of Takotsubo cardiomyopathy triggered by influenza A virus. Myocardial involvement in influenza virus infection has been described in 10% of cases. The literature has principally reported cases of acute myocarditis ranging from asymptomatic to fulminant heart failure and cardiac tamponade. Takotsubo cardiomyopathy frequently occurs in the setting of significant emotional or physical stress or acute medical illness, with a predominance in postmenopausal women. We report the diagnosis, management and outcomes presented in this case, with the aim of describing a new cardiovascular complication of influenza virus infection. PMID- 26278295 TI - Infective Internal Iliac Artery Aneurysm Caused by Campylobacter fetus. AB - A 67-year-old man with a persistent high fever was diagnosed to have an infective aneurysm in his left internal iliac artery. A blood culture detected a gram negative spiral rod that was first identified as Campylobacter fetus subsp. venerealis based on a matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) analysis. However, the strain was finally confirmed to be Campylobacter fetus subsp. fetus based on a genetic analysis. The infection was successfully treated with emergency resection of the aneurysm, followed by 4 weeks of antibiotic therapy. Involvement of the peripheral artery is uncommon in cases of C. fetus-infective aneurysm. To figure out the epidemiology and pathogenicity of C. fetus infection, the accurate identification of the responsible organisms is essential. PMID- 26278296 TI - Acute Multiple Arteriovenous Thromboses in a Patient with Diabetic Ketoacidosis. AB - Diabetic ketoacidosis (DKA) is one of the most serious acute complications of diabetes mellitus. An arterial thrombotic tendency from DKA is relatively common; however, the occurrence of acute multiple arteriovenous thromboses is rare. We herein report the case of a 49-year-old man with DKA complicated by multiple thromboses. After transfer to our emergency room with DKA, the patient developed sudden abdominal pain. Contrast-enhanced computed tomography revealed near complete occlusion of the superior mesenteric artery, superior mesenteric vein, splenic artery, and right femoral artery. This occurrence highlights the need for considering the risk of thrombosis during the initial treatment for DKA. PMID- 26278297 TI - Primary Antiphospholipid Syndrome Associated with Diffuse Alveolar Hemorrhage and Pulmonary Thromboembolism. AB - Antiphospholipid syndrome (APS) is clinically characterized by arterial or venous thrombosis; however, non-thromboembolic lung manifestations, such as diffuse alveolar hemorrhage (DAH), have also been previously reported. DAH is relatively common in APS patients with systemic lupus erythematosus, although it is rare in primary APS. We encountered a 78-year-old man who presented with hemoptysis and dyspnea. Chest CT showed diffuse ground-glass opacity with pulmonary thromboembolism. He was successfully treated with corticosteroids and heparin; however, DAH recurred after the corticosteroid treatment was stopped. The treatment was intricate due to the concurrent bleeding and thrombotic manifestations. PMID- 26278298 TI - Pulmonary Aluminosis Diagnosed with In-air Microparticle Induced X-ray Emission Analysis of Particles. AB - We herein present a case of pulmonary aluminosis diagnosed with in-air microparticle induced X-ray emission (in-air micro-PIXE) analysis. The diagnosis of pulmonary aluminosis was supported by the occupational exposure to aluminum, ground glass opacity and ill-defined centrilobular nodular opacities seen in high resolution CT, and respiratory bronchioles accompanied by pigmented dust by histological examination by in-air micro-PIXE analysis of the lung tissues. The possibility of developing this rare condition should not be underestimated in workers at high-risk jobs. This is an important report showing the usefulness of an in-air micro-PIXE analysis for the early diagnosis of aluminosis. PMID- 26278299 TI - Mucosa-associated Lymphoid Tissue Lymphoma of the Trachea in a Patient with Breast Cancer. AB - We herein report the case of a 93-year-old woman with breast cancer on the left side. Preoperative computed tomography of the chest showed irregularities and narrowing of the mid-trachea. Bronchoscopy was performed, and the results of a biopsy supported a diagnosis of mucosa-associated lymphoid tissue (MALT) lymphoma. The patient responded to treatment with prednisone alone, with a reduction in the size of the lesion. MALT lymphoma of the trachea is extremely rare, and there are only a few case reports of double cancer, i.e., MALT lymphoma of the trachea and breast cancer. PMID- 26278300 TI - Hypertrophic Pulmonary Osteoarthropathy in Anaplastic Lymphoma Kinase (ALK) positive Lung Cancer. AB - A 49-year-old man was admitted to a hospital with chest pain and polyarthralgia. Chest radiography showed abnormal findings, and chest computed tomography showed a mass in the right lung. A transbronchial lung biopsy led to a diagnosis of anaplastic lymphoma kinase (ALK)-positive adenocarcinoma. Bone scintigraphy revealed bilateral symmetrical accumulations of (99m)Technetium complexes in the long bones, suggesting co-existing hypertrophic pulmonary osteoarthropathy (HPO). The patient underwent four courses of chemotherapy with cisplatin plus pemetrexed, which led to decreased (99m)Technetium accumulations in the long bones. To the best of our knowledge, this is the first reported case of HPO associated with ALK-positive lung cancer. PMID- 26278301 TI - Primary Pleural Synovial Sarcoma Treated with Pazopanib. AB - A 42-year-old woman presented with chest pain and breathlessness with a nodule measuring 2*2 cm in size at the base of the right lung. A bronchoscopic examination did not reveal any malignancy. However, the patient developed difficulty in breathing, enlargement of the nodule, and right pleural effusion 14 days later. A video-assisted thoracic surgical biopsy specimen revealed the presence of pleural synovial sarcoma. The patient was treated with doxorubicin ifosfamide combination chemotherapy because of metastasis to the pelvis. However, after a transient partial clinical response, there was a relapse of refractory disease. Although treated with pazopanib as second-line chemotherapy, the patient died eight months after the initial presentation. PMID- 26278302 TI - Rhabdomyolysis Caused by Candida parapsilosis in a Patient with Acute Myeloid Leukemia after Bone Marrow Transplantation. AB - Rhabdomyolysis is characterized by a marked elevation of the creatine kinase (CK) levels and myoglobinuria, thus leading to renal dysfunction. Various viruses or bacteria can be etiologic agents, but mycosis has only rarely been reported to be a cause of rhabdomyolysis. In this report, we describe an adolescent male with acute myeloid leukemia who underwent allogeneic bone marrow transplantation and thereafter developed rhabdomyolysis and Candida parapsilosis fungemia almost at the same time. Following treatment for C. parapsilosis, the transaminase and CK levels both satisfactorily decreased. This case illustrates that C. parapsilosis infection may be a causative agent of rhabdomyolysis in immunocompromised patients. PMID- 26278303 TI - Pulmonary Extranodal Marginal Zone Lymphoma with Macroglobulinemia and Mixed Cryoglobulinemia Developed in a Patient with Chronic Hepatitis C. AB - We report a 65-year-old woman with a chronic hepatitis C virus infection who developed pulmonary extranodal marginal zone lymphoma (EMZL) of mucosa-associated lymphoid tissues complicated with macroglobulinemia and mixed cryoglobulinemia. She was treated with immunochemotherapy which resulted in the reduction of both the tumors and the serum immunoglobulin (Ig) M level. This case exemplifies an extensive stimulation upon immune system with derangement in the production of immunoglobulines associated with EMZL, and suggests that it is necessary to consider the possibility of B-cell lymphoma when IgM paraprotein is detected. PMID- 26278304 TI - Varicella Zoster Virus Meningoencephalitis Presenting with Elsberg Syndrome without a Rash in an Immunocompetent Patient. AB - Varicella zoster virus (VZV) infection usually manifests with a skin rash. To the best of our knowledge, this is the first report of a case of VZV meningoencephalitis presenting with Elsberg syndrome without a rash in an immunocompetent patient. Clinicians should consider the potential for VZV infection as well as herpes simplex virus infection in cases of aseptic meningitis accompanied by bladder and rectal disturbances, even in patients without any rash symptoms. PMID- 26278305 TI - A Case Presenting with the Clinical Characteristics of Tumor Necrosis Factor (TNF) Receptor-associated Periodic Syndrome (TRAPS) without TNFRSF1A Mutations Successfully Treated with Tocilizumab. AB - A 30-year-old woman had suffered from recurrent and self-limiting fevers since childhood. Although she had no mutations in the exons or introns of the tumor necrosis factor (TNF) receptor superfamily member 1A gene, her clinical characteristics were consistent with those of TNF receptor-associated periodic syndrome (TRAPS). She did not respond to treatment with etanercept, although tocilizumab therapy was successful, subsequently ameliorating her symptoms and preventing further inflammatory attacks. Interleukin-6 blocking therapy should be considered as a new alternative treatment in patients with TRAPS who do not respond to etanercept. PMID- 26278306 TI - Life Threatening, Allopurinol-related Dress Syndrome as a Rare Cause of Fever of Unknown Origin. AB - Drug reaction eosinophilia with systemic symptoms (DRESS) syndrome is a potentially life threatening condition secondary to the usage of a wide type of drugs. A 38-year-old woman under allopurinol therapy for hyperuricemia was admitted in our department with fever and a diffuse cutaneous erythematous eruption. A few days after admission she developed rapidly progressive signs of acute liver and kidney failure. Subsequently, her clinical conditions shortly improved. The histologic findings obtained from skin and liver biopsies were consistent with a toxic drug reaction. The patient completely recovered and has been healthy for five years. PMID- 26278307 TI - Decreasing Liver Stiffness Following Pericardiectomy for Constrictive Pericarditis. PMID- 26278308 TI - Massive Barium Sulfate Aspiration in the Bronchial Tree. PMID- 26278309 TI - Periungual Hemorrhage with Rapid Progressive Interstitial Pneumonia. PMID- 26278310 TI - Multiple Myeloma Mimicking Liver Metastases. PMID- 26278311 TI - Double Herpes Zoster in a Hemodialysis Patient. PMID- 26278312 TI - Yellow Nail Syndrome in Toenails. PMID- 26278314 TI - Nocardia farcinica Pneumonia in a Palliative Care Unit. PMID- 26278313 TI - Rheumatoid Vasculitis. PMID- 26278315 TI - Transient Eosinophilia with Catastrophic Vessel Occlusion. PMID- 26278316 TI - Cerebral Sinovenous Thrombosis in a Patient with Transient Eosinophilia. PMID- 26278317 TI - Safe staffing and the global mandate for health. PMID- 26278318 TI - Prenatal Exposure to Continuous Constant Light Alters Endochondral Ossification of the Tibiae of Rat Pups. AB - Clinical and experimental studies suggest that prenatal exposure to stress can impact the growth and development of offspring. The effect of prenatal exposure to constant light, applied as a chronic stressor, on endochondral ossification of the tibiae of 3-day-old and 15-day-old pups was histomorphometrically evaluated. Pregnant rats were divided into 2 groups: mothers chronically exposed to a 12:12 hour light/light cycle (LL) and control mothers maintained on a 12:12-hour light/dark cycle on days 10-20 of pregnancy. On postnatal days 3 and 15, the pups were weighed and euthanized. The tibiae were resected and histologically processed to obtain sections for hematoxylin and eosin staining (HE) and tartrate resistant acid phosphatase (TRAP) histochemistry, in order to perform histomorphometric determinations. The data were statistically analyzed. A significant decrease in hypertrophic cartilage thickness was observed in the tibiae of the 3-day-old (LL: 0.134 +/- 0.02 vs. CONTROLS: 0.209 +/- 0.023 mm; p < 0.01) and 15-day-old (LL: 23.32 +/- 3.98 vs. CONTROLS: 22.96 +/- 1.93 mm; p < 0.05) prenatally stressed pups. The subchondral bone volume was significantly lower in the tibiae of the 3-day-old LL pups (38.83 +/- 6.14%) than in the controls (62.83 +/- 10.67%; p < 0.01). The decrease in subchondral bone volume and hypertrophic cartilage thickness shows that the normal growth process of the tibia is impaired in prenatally stressed pups. PMID- 26278319 TI - Twenty-Five Years of Fetoscopic Laser Coagulation in Twin-Twin Transfusion Syndrome: A Systematic Review. AB - OBJECTIVE: The aim of this study was to assess the perinatal outcome of pregnancies with twin-twin transfusion syndrome (TTTS) treated with laser therapy over the past 25 years, and in relation to different techniques used in this time period. METHODS: A systematic review of studies reporting on perinatal outcome according to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines was conducted. The MEDLINE, Embase and Cochrane Library databases were systematically searched. Comparisons were made in respect to time period and laser technique and Quintero stages. RESULTS: In total, 34 studies reporting on 3,868 monochorionic twin pregnancies were included. The mean survival of both twins increased from 35 to 65% (p = 0.012) and for at least one twin from 70 to 88% (p = 0.009) over the past 25 years. Mean gestational age at birth remained stable over the years at 32 weeks gestation. Also, we showed a significantly improved perinatal survival with the evolution of the laser technique from non selective to selective, selective sequential and the Solomon technique (p = 0.010). DISCUSSION: Since the introduction of laser therapy for TTTS more than two decades ago, perinatal survival improved significantly. Improved outcome is probably associated with several factors, including evolution of the laser technique, learning curve effect, better referral and improved early neonatal care. PMID- 26278320 TI - Disparities in care for patients with curable hepatocellular carcinoma. PMID- 26278321 TI - Disparities in care for patients with curable hepatocellular carcinoma. AB - BACKGROUND: The incidence of hepatocellular carcinoma (HCC) is increasing, but surgical management continues to be underutilized. This retrospective review investigates treatment decisions and survival for early stage HCC. METHODS: The National Cancer Database (NCDB) was queried for all patients with curable HCC (Stage I/II) from 1998 to 2011 (n = 43 859). Patient and tumour characteristics were analysed to determine predictors of having surgery and of long-term survival. RESULTS: Only 39.7% of patients received surgery for early stage HCC. Surgical therapies included resection (34.6%), transplant (28.7%), radiofrequency ablation (27.1%) and other therapies. Surgery correlated with improved median survival (48.3 versus 8.4 months), but was only performed on 42% of stage I patients and 50% of tumours smaller than 2 cm. Patients were more likely to receive surgery if they were Asian or white race, had private insurance, higher income, better education, or treatment at an academic centre (P < 0.05). However, private insurance and treatment at an academic centre were the only variables associated with improved survival (P < 0.05). CONCLUSION: Fewer than half of patients with curable HCC receive surgery, possibly as a result of multiple socioeconomic variables. Past these barriers to care, survival is related to adequate and reliable treatment. Further efforts should address these disparities in treatment decisions. PMID- 26278322 TI - The impact of portal pedicle clamping on survival from colorectal liver metastases in the contemporary era of liver resection: a matched cohort study. AB - INTRODUCTION: Portal pedicle clamping (PPC) may impact micro-metastases' growth. This study examined the association between PPC and survival after a hepatectomy for colorectal liver metastases (CRLM). METHODS: A matched cohort study was conducted on hepatectomies for CRLM at a single institution (2003-2012). Cohorts were selected based on PPC use, with 1:1 matching for age, time period and the Clinical Risk Score. Outcomes were overall and recurrence-free survival (OS and RFS). Cox regression was performed to assess the association between PPC and survival. RESULTS: Of 481 hepatectomies, 26.9% used PPC. One hundred and ten pairs of patients were matched in the cohorts. There was no significant difference in OS [hazard ratio (HR) 1.18; 95% confidence interval (CI): 0.76 1.83], with a 5-year OS of 57.8% (95%CI: 52.4-63.2%) with PPC versus 62.3% (95%CI: 57.1-67.5%) without. Five-year RFS did not differ (HR 0.98; 95%CI: 0.71 1.35) with 29.7% (95%CI: 24.9-34.5%) with PPC versus 28.0% (95%CI: 23.2-32.8%) without. When adjusting for extent of resection, transfusion, operative time and surgeon, there was no difference in OS (HR 0.91; 95%CI: 0.52-1.60) or RFS (HR: 0.86; 95%CI: 0.57-1.30). CONCLUSIONS: PPC was not associated with a significant difference in OS or RFS in a hepatectomy for CRLM. PPC remains a safe technique during hepatectomy. PMID- 26278323 TI - Clinical and pathological features of intraductal papillary neoplasm of the biliary tract and gallbladder. AB - BACKGROUND: Intraductal papillary neoplasms of the biliary tract (IPNB) and intracholecystic papillary neoplasms (ICPN) are rare tumours characterized by intraluminal papillary growth that can be associated with invasive carcinoma. Their natural history remains poorly understood. This study examines clinicopathological features and outcomes. METHODS: Patients who underwent surgery for IPNB/ICPN (2008-2014) were identified. Descriptive statistics and survival data were generated. RESULTS: Of 23 patients with IPNB/ICPN, 10 were male, and the mean age was 68 years. The most common presentations were abdominal pain (n = 10) and jaundice (n = 9). Tumour locations were: intrahepatic (n = 5), hilar (n = 3), the extrahepatic bile duct (n = 8) and the gallbladder (n = 7). Invasive cancer was found in 20/23 patients. Epithelial subtypes included pancreatobiliary (n = 15), intestinal (n = 7) and gastric (n = 1). The median follow-up was 30 months. The 5-year overall (OS) and disease-free survivals (DFS) were 51% and 57%, respectively. Decreased OS (P = 0.09) and DFS (P = 0.05) were seen in patients with tumours expressing MUC1 on immunohistochemistry (IHC). CONCLUSION: IPNB/ICPN are rare precursor lesions that can affect the entire biliary epithelium. At pathology, the majority of patients have invasive carcinoma, thus warranting a radical resection. Patients with tumours expressing MUC1 appear to have worse OS and DFSs. PMID- 26278326 TI - Enlarged Optic Nerve Sheath in Aneurysmal Subarachnoid Hemorrhage despite Normal Intracranial Pressure. AB - INTRODUCTION: This study investigates the diagnostic value of optic nerve sheath diameter (ONSD) assessed by transorbital sonography for estimation of intracranial pressure (ICP) in patients with aneurysmal subarachnoid hemorrhage (SAH). METHODS: Simultaneous measurements of the ONSD and ICP in 27 patients suffering from SAH and acute hydrocephalus after placement of an extraventricular drain. RESULTS: Despite normal mean ICP values ONSD was significantly higher in patients with SAH compared with healthy volunteers and no relevant decline of ONSD over time could be identified. In addition, no correlation between ONSD and ICP was observed. CONCLUSIONS: In patients with SAH and acute hydrocephalus after aneurysm rupture, the ONSD remains expanded after normalization of ICP. This is most likely due to an impaired retraction capability of the optic nerve sheath. This finding should be considered when using transorbital sonography in the neuromonitoring of aneurysmal SAH. PMID- 26278327 TI - Hypnotics and Triazolobenzodiazepines--Best Predictors of High-Dose Benzodiazepine Use: Results from the Luxembourg National Health Insurance Registry. AB - BACKGROUND: Benzodiazepines are not all the same concerning their risk of high dose use. METHODS: We studied benzodiazepine use from the Luxembourg national records of all insured. We calculated the 12-year prevalence from 1995 to 2007. Benzodiazepine users were divided into 3 groups, short-term with no longer than 3 month intake, intermediate with multiple administration with at least a 1-year interruption, and continuous who never stopped. A high-dose user (HDU) was defined as a patient who received a higher dose than the yearly maximum usual therapeutic dose. RESULTS: An average of 16.0% of the adult insured population received at least 1 benzodiazepine annually, 42.9% were older than 50, 55.9% were women, and 5.4% were HDUs. We found that 32.6% were short-term users, 49.0% intermediate and 18.4% continuous. Compared to diazepam, hypnotics had higher risks for high-dose use in at least 1 age group at first-benzodiazepine intake, the risks being greater in elderly subjects and women, the highest risks being with triazolam (adjusted odds ratio = 215.85; 95% confidence interval = 133.75 348.35) in the 69- to 105-year-old group at first-benzodiazepine intake. Anxiolytics had a low risk except for alprazolam and prazepam in the 69- to 105 year-old group at first-benzodiazepine intake, clonazepam and clobazam had the lowest risk in 18- to 43-year-olds at first-benzodiazepine intake. Alprazolam had dispensed volumes increased by threefold over the 12-year period. CONCLUSION: All hypnotics had higher risks for high-dose use compared to diazepam in continuous users. Two anxiolytics, clonazepam and clobazam, had the lowest risks. Hypnotics and the triazolobenzodiazepines alprazolam and triazolam were most problematic. Elderly subjects and women are at greater risks. PMID- 26278328 TI - Aberrant Placental Villus Expression of miR-486-3p and miR-3074-5p in Recurrent Miscarriage Patients and Uterine Expression of These MicroRNAs during Early Pregnancy in Mice. AB - MicroRNAs (miRNAs) are critical regulators of gene expression; they have emerged as new players in the pathophysiology of reproductive disorders such as preeclampsia and recurrent miscarriage (RM). In this study, miRNA expression profiles were determined by deep sequencing analysis in placental villi obtained from women with RM and with gestational age-matched normal pregnancy (NP). A total of 69 miRNAs were found to be aberrantly expressed in RM. Five of these human (Homo sapiens) miRNAs (hsa-miRNAs), including hsa-miR-3074-5p, -486-3p, 1269b, -6765-3p and -144-3p, were validated by qRT-PCR in 12 RM and 10 NP placental villi. Hsa-miR-3074-5p expression was significantly higher, while hsa miR-486-3p expression was significantly lower, in RM compared to NP. Subsequently, the expression of mouse (Mus musculus) miR-486-3p (mmu-miR-486-3p) and mmu-miR-3074-5p, which are identical to hsa-miR-486-3p and hsa-miR-3074-5p, respectively, were examined by qRT-PCR in the uterus during early pregnancy. Mmu miR-486-3p expression was significantly increased during the peri-implantation period, and the levels were significantly higher at implantation than at non implantation sites. In contrast, the expression of mmu-miR-3074-5p was markedly decreased at implantation compared to non-implantation sites. These data suggest that miR-486-3p and miR-3074-5p may be involved in embryo implantation and that their aberrant expression is associated with RM. Larger studies are warranted to follow up this pilot study. (c) 2015 S. Karger AG, Basel. PMID- 26278329 TI - Social networks of older adults living with HIV in Finland. AB - The aim of this study was to explore the social networks of older adults living with HIV. Interviews were conducted with nine individuals aged 50 or older living with HIV in Helsinki, Finland. Analysis of transcripts was analysed by inductive qualitative content analysis. Results indicated that these participants' networks tended to be large, including those both aware and unaware of the participants' health status. Analysis identified three main themes: large multifaceted social networks, importance of a support group, and downsizing of social networks. Support received appeared to be of great importance in coping with their health condition, especially since the time of diagnosis. Friends and family were the primary source of informal support. The majority of participants relied mostly on friends, some of whom were HIV-positive. Formal support came primarily from the HIV organisation's support group. In this study group, non-disclosure did not impact participants' well-being. In years to come, social networks of older adults living with HIV may shrink due to personal reasons other than HIV disclosure. What is of primary importance is that healthcare professionals become knowledgeable about psychosocial issues of older adults living with HIV, identifying latent problems and developing adequate interventions in the early stages of the disease; this would help prevent social isolation and foster successful ageing with HIV. PMID- 26278330 TI - Delivery of siRNA Using CXCR4-targeted Nanoparticles Modulates Tumor Microenvironment and Achieves a Potent Antitumor Response in Liver Cancer. AB - Antiangiogenic therapy has recently emerged as a highly promising therapeutic strategy for treating hepatocellular carcinoma (HCC). However, the only clinically approved systemic antiangiogenic agent for advanced HCC is sorafenib, which exerts considerable toxicity. Moreover, acquired resistance to antiangiogenic therapy often develops and restricts the therapeutic efficacy of this treatment. Hence, in this study, we develop a CXCR4-targeted lipid-based nanoparticle (NP) formulation to specifically deliver vascular endothelial growth factor (VEGF) siRNA as an antiangiogenic substance into HCC. AMD3100, a CXCR4 antagonist, is added into NPs to serve as both a targeting moiety and a sensitizer to antiangiogenic therapy. We demonstrate that AMD-modified NPs (AMD NPs) can efficiently deliver VEGF siRNAs into HCC and downregulate VEGF expression in vitro and in vivo. Despite the upregulation of the SDF1alpha/CXCR4 axis upon the induction of hypoxia after antiangiogenic therapy, CXCR4 inhibition by AMD-NPs in combination with either conventional sorafenib treatment or VEGF siRNA prevents the infiltration of tumor-associated macrophages. These dual treatments also induce synergistic antiangiogenic effects and suppress local and distant tumor growth in HCC. In conclusion, the tumor-targeted multifunctional AMD-NPs that co-deliver VEGF siRNA and AMD3100 provide an effective approach for overcoming tumor evasion of antiangiogenic therapy, leading to delayed tumor progression in HCC. PMID- 26278331 TI - The Role of Neutrophils in Measles Virus-mediated Oncolysis Differs Between B cell Malignancies and Is Not Always Enhanced by GCSF. AB - The mechanism by which oncolytic measles virus (MV) kills cancer cells remains obscure. We previously showed that neutrophils are involved in MV-mediated tumor regressions and become activated, upon MV infection. In the present study, we attempted to enhance the neutrophil response toward MV-infected tumor targets by generating an oncolytic MV-expressing human granulocyte colony-stimulating factor (MVhGCSF). Evaluating the effects in two different models of B-cell malignancy, we showed that depletion of neutrophils abrogated the MV therapeutic effect in an in vivo Raji-but not Nalm-6 tumor model. Next, we compared MVhGCSF with the unmodified backbone virus MVNSe. MVhGCSF enhanced the oncolytic capacity of MV in the Raji model in vivo, whereas in the Nalm-6 model, the opposite was unexpectedly the case. This finding was recapitulated by exogenously administered hGCSF. MVhGCSF replicated within an MV-infectable CD46 transgenic mouse model with detectable serum levels of hGCSF but no toxicity. Our data suggest that a "one-size-fits-all" model of immune response to viral oncolysis is not appropriate, and each tumor target will need full characterization for the potential of both direct and indirect, innate immune responses to generate benefit. PMID- 26278332 TI - Nano-encapsulated PCM via Pickering Emulsification. AB - We designed a two-step Pickering emulsification procedure to create nano encapsulated phase changing materials (NEPCMs) using a method whose simplicity and low energy consumption suggest promise for scale-up and mass production. Surface-modified amphiphilic zirconium phosphate (ZrP) platelets were fabricated as the Pickering emulsifiers, nonadecane was chosen as the core phase change material (PCM), and polystyrene, the shell material. The resultant capsules were submicron in size with remarkable uniformity in size distribution, which has rarely been reported. Differential scanning calorimetry (DSC) characterization showed that the capsulation efficiency of NEPCMs, and they were found to be thermal stable, as characterized by the DSC data for the sample after 200 thermal cycles. NEPCMs exhibit superior mechanical stability and mobility when compared with the well-developed micro-encapsulated phase change materials (MEPCMs). NEPCMs find useful applications in thermal management, including micro-channel coolants; solar energy storage media; building temperature regulators; and thermal transfer fabrics. PMID- 26278333 TI - Co-extinction in a host-parasite network: identifying key hosts for network stability. AB - Parasites comprise a substantial portion of total biodiversity. Ultimately, this means that host extinction could result in many secondary extinctions of obligate parasites and potentially alter host-parasite network structure. Here, we examined a highly resolved fish-parasite network to determine key hosts responsible for maintaining parasite diversity and network structure (quantified here as nestedness and modularity). We evaluated four possible host extinction orders and compared the resulting co-extinction dynamics to random extinction simulations; including host removal based on estimated extinction risk, parasite species richness and host level contributions to nestedness and modularity. We found that all extinction orders, except the one based on realistic extinction risk, resulted in faster declines in parasite diversity and network structure relative to random biodiversity loss. Further, we determined species-level contributions to network structure were best predicted by parasite species richness and host family. Taken together, we demonstrate that a small proportion of hosts contribute substantially to network structure and that removal of these hosts results in rapid declines in parasite diversity and network structure. As network stability can potentially be inferred through measures of network structure, our findings may provide insight into species traits that confer stability. PMID- 26278334 TI - Hierarchical Co-based Porous Layered Double Hydroxide Arrays Derived via Alkali Etching for High-performance Supercapacitors. AB - Hierarchical nanoarchitecture and porous structure can both provide advantages for improving the electrochemical performance in energy storage electrodes. Here we report a novel strategy to synthesize new electrode materials, hierarchical Co based porous layered double hydroxide (PLDH) arrays derived via alkali etching from Co(OH)2@CoAl LDH nanoarrays. This structure not only has the benefits of hierarchical nanoarrays including short ion diffusion path and good charge transport, but also possesses a large contact surface area owing to its porous structure which lead to a high specific capacitance (23.75 F cm(-2) or 1734 F g( 1) at 5 mA cm(-2)) and excellent cycling performance (over 85% after 5000 cycles). The enhanced electrode material is a promising candidate for supercapacitors in future application. PMID- 26278335 TI - Reward feedback stimuli elicit high-beta EEG oscillations in human dorsolateral prefrontal cortex. AB - Reward-related feedback stimuli have been observed to elicit a burst of power in the beta frequency range over frontal areas of the human scalp. Recent discussions have suggested possible neural sources for this activity but there is a paucity of empirical evidence on the question. Here we recorded EEG from participants while they navigated a virtual T-maze to find monetary rewards. Consistent with previous studies, we found that the reward feedback stimuli elicited an increase in beta power (20-30 Hz) over a right-frontal area of the scalp. Source analysis indicated that this signal was produced in the right dorsolateral prefrontal cortex (DLPFC). These findings align with previous observations of reward-related beta oscillations in the DLPFC in non-human primates. We speculate that increased power in the beta frequency range following reward receipt reflects the activation of task-related neural assemblies that encode the stimulus-response mapping in working memory. PMID- 26278336 TI - Metabolic syndrome and aerobic fitness in patients with first-episode schizophrenia, including a 1-year follow-up. AB - OBJECTIVE: To compare the prevalence of metabolic syndrome (MetS) and metabolic abnormalities in patients with first-episode schizophrenia (FES) with sex- and age-matched healthy controls; to investigate changes in MetS during 1year of treatment; and to investigate predictors of MetS. METHODS: Patients with FES (N=99) and healthy controls (N=50) were included in the study. MetS was defined according to IDF based on waist circumference (WC), blood pressure (BP), triglycerides (TG), high-density lipoprotein (HDL), and fasting-glucose. Data on physical activity, aerobic fitness, smoking, and dietary habits, sleeping disturbances, psychopathology and psychotropic medication were also obtained. Patients were assessed at baseline and at 1year follow-up. RESULTS: Compared with healthy controls patients with FES had a higher baseline prevalence of MetS (p=.07), and metabolic abnormalities: WC (p<.01), TG (p<.01), HDL (p=.017), and fasting glucose (p=.04). Patients with FES had significantly increased prevalence of MetS (p=.03), WC (p=.04), and TG (p=.01) during the study period. Antipsychotics and low physical activity were significantly correlated with the increase in metabolic abnormalities. In multivariate analyses low aerobic fitness was the most consistent and significant predictor of metabolic abnormalities and MetS. CONCLUSION: MetS and metabolic abnormalities are highly prevalent in patients with FES, and both increase significantly during 1year of treatment. Apart from confirming the metabolic adverse effects of antipsychotics, our study highlights that low aerobic fitness is a significant risk factor for MetS. Promoting a healthier lifestyle should be part of psychiatric treatment and rehabilitation. PMID- 26278337 TI - Transfer Effect of Speech-sound Learning on Auditory-motor Processing of Perceived Vocal Pitch Errors. AB - Speech perception and production are intimately linked. There is evidence that speech motor learning results in changes to auditory processing of speech. Whether speech motor control benefits from perceptual learning in speech, however, remains unclear. This event-related potential study investigated whether speech-sound learning can modulate the processing of feedback errors during vocal pitch regulation. Mandarin speakers were trained to perceive five Thai lexical tones while learning to associate pictures with spoken words over 5 days. Before and after training, participants produced sustained vowel sounds while they heard their vocal pitch feedback unexpectedly perturbed. As compared to the pre training session, the magnitude of vocal compensation significantly decreased for the control group, but remained consistent for the trained group at the post training session. However, the trained group had smaller and faster N1 responses to pitch perturbations and exhibited enhanced P2 responses that correlated significantly with their learning performance. These findings indicate that the cortical processing of vocal pitch regulation can be shaped by learning new speech-sound associations, suggesting that perceptual learning in speech can produce transfer effects to facilitating the neural mechanisms underlying the online monitoring of auditory feedback regarding vocal production. PMID- 26278338 TI - Performance of the Delirium Rating Scale-Revised-98 Against Different Delirium Diagnostic Criteria in a Population With a High Prevalence of Dementia. AB - BACKGROUND: Delirium diagnosis in elderly is often complicated by underlying dementia. OBJECTIVE: We evaluated performance of the Delirium Rating Scale Revised-98 (DRS-R98) in patients with high dementia prevalence and also assessed concordance among past and current diagnostic criteria for delirium. METHODS: Cross-sectional analysis of newly admitted patients to a skilled nursing facility over 6 months, who were rated within 24-48 hours after admission. Interview for Diagnostic and Statistical Manual of Mental Disorders, 3rd edition-R (DSM)-III-R, DSM-IV, DSM-5, and International Classification of Diseases 10th edition delirium ratings, administration of the DRS-R98, and assessment of dementia using the Informant Questionnaire on Cognitive Decline in the Elderly were independently performed by 3 researchers. Discriminant analyses (receiver operating characteristics curves) were used to study DRS-R98 accuracy against different diagnostic criteria. Hanley and McNeil test compared the area under the curve for DRS-R98's discriminant performance for all diagnostic criteria. RESULTS: Dementia was present in 85/125 (68.0%) subjects, and 36/125 (28.8%) met criteria for delirium by at least 1 classification system, whereas only 19/36 (52.8%) did by all. DSM-III-R diagnosed the most as delirious (27.2%), followed by DSM-5 (24.8%), DSM-IV-TR (22.4%), and International Classification of Diseases 10th edition (16%). DRS-R98 had the highest AUC when discriminating DSM-III-R delirium (92.9%), followed by DSM-IV (92.4%), DSM-5 (91%), and International Classification of Diseases 10th edition (90.5%), without statistical differences among them. The best DRS-R98 cutoff score was >=14.5 for all diagnostic systems except International Classification of Diseases 10th edition (>=15.5). CONCLUSIONS: There is a low concordance across diagnostic systems for identification of delirium. The DRS-R98 performs well despite differences across classification systems perhaps because it broadly assesses phenomenology, even in this population with a high prevalence of dementia. PMID- 26278339 TI - Comparison of Electronic Screening for Suicidal Risk With the Patient Health Questionnaire Item 9 and the Columbia Suicide Severity Rating Scale in an Outpatient Psychiatric Clinic. AB - BACKGROUND: Patient-reported data can improve clinical care, including identifying patients who are at risk for suicide. METHODS: In a tertiary care, psychiatric outpatient clinic, we compared computerized self-assessments of suicidal risk based on item 9 of the Patient Health Questionnaire-9 and an electronic version of the Columbia Suicide Severity Rating Scale (C-SSRS), using retrospective medical record review of clinical psychiatric assessments as the reference standard. We also surveyed patients' attitudes about participating in the process. We compared prevalence of suicidal risk rates by the 3 assessment methods as well as their sensitivity, specificity, and predictive value. RESULTS: Observed prevalence of positive suicidal risk screenings differed significantly, ranking (1) Patient Health Questionnaire-9 item 9, 24% (343/1416; 95% CI: 22% 26%) < (2) C-SSRS, 6.0% (85/1416; 95% CI: 5.0%-7.4%) < (3) clinical assessment, 1.4% (20/1416; 95% CI: 0.9%-2.2%). The sensitivity of Patient Health Questionnaire-9 item 9 was 92% (78/85; 95% CI: 86%-98%) and the specificity was 81% (1107/1376; 95% CI: 78%-82%). The sensitivity of the C-SSRS was 95.0% (19/20; 95% CI: 75%-100%) and the specificity was 95% (1330/1396; 95% CI: 94%-96%). Of 100 patients surveyed, the screening was well accepted, with some concerns about confidentiality and adequate clinical follow-up. CONCLUSIONS: As expected, Patient Health Questionnaire-9 item 9 generated much higher rates of apparently false-positive findings than the C-SSRS did, when compared with clinical assessment. C-SSRS backed with timely clinical assessment may be a useful and efficient method of screening for suicidal risk, provided that adequate, immediate clinical follow-up is available. PMID- 26278340 TI - Free open access medical education can help rural clinicians deliver 'quality care, out there'. AB - Rural clinicians require expertise across a broad range of specialties, presenting difficulty in maintaining currency of knowledge and application of best practice. Free open access medical education is a new paradigm in continuing professional education. Use of the internet and social media allows a globally accessible crowd-sourced adjunct, providing inline (contextual) and offline (asynchronous) content to augment traditional educational principles and the availability of relevant resources for life-long learning. This markedly reduces knowledge translation (the delay from inception of a new idea to bedside implementation) and allows rural clinicians to further expertise by engaging in discussion of cutting edge concepts with peers worldwide. PMID- 26278341 TI - Development of a Primary Care-Based Clinic to Support Adults With a History of Childhood Cancer: The Tactic Clinic. AB - PURPOSE: Describe the development and evolution of a primary-care-based, multidisciplinary clinic to support the ongoing care of adult survivors of childhood cancer. METHODS: A consultative clinic for adult survivors of childhood cancer has been developed that is located in an adult, academic internal medicine setting and is based on a long-term follow-up clinic model available at Children's Hospital Colorado. RESULTS: The clinic opened in July 2008. One hundred thirty-five patients have been seen as of April 2014. Referrals and clinic capacity have gradually increased over time, and a template has been developed in the electronic medical record to help facilitate completion of individualized care plan letters. CONCLUSIONS: A primary care-based, multidisciplinary consultative clinic for adults with a history of childhood cancer survivor is feasible and actively engages adult primary care resources to provide risk-based care for long-term pediatric cancer survivors. This model of care planning can help support adult survivors of pediatric cancer and their primary care providers in non-academic, community settings as well. PMID- 26278342 TI - New Techniques in Pediatric Pain Management: Continuous Peripheral Nerve Block. PMID- 26278343 TI - In vivo prediction of CYP-mediated metabolic interaction potential of formononetin and biochanin A using in vitro human and rat CYP450 inhibition data. AB - Formononetin (FMN) and Biochanin A (BCA) are the principal isoflavones present in commercially available extracts of red clover that are widely been consumed for various health benefits. We investigated the in vitro effects of FMN and BCA on catalytic activity of human/rat cytochrome P450 enzymes to assess the drug interaction potential of red clover. IC50 and Ki values of FMN and BCA for CYPs were determined in human/rat liver microsomes. FMN and BCA showed concentration dependent inhibition of CYP1A2 activity with IC50 values of 13.42 and 24.98MUM in human liver microsomes and 38.57 and 11.86MUM in rat liver microsomes, respectively. The mode of inhibition of human CYP1A2 by FMN was found to be competitive with apparent Ki value of 10.13+/-1.96MUM. FMN also inhibited human CYP2D6. BCA exerted moderately inhibitory effects on human CYP2C9. The predicted in vivo inhibition for CYP1A2 was insignificant (R value <1.1) at hepatic level while at intestinal level, it was significant (R value >11). The inhibitory effects on other CYPs were found to be minimal. Red clover may be considered safe to be consumed along with co-prescribed medications; however, precaution must be taken while co-administering it with CYP1A2 substrates. PMID- 26278344 TI - Editorial overview: Anti-infectives: Current challenges and unmet needs in antimicrobial therapy. PMID- 26278345 TI - Evolution of Hox-like genes in Cnidaria: Study of Hydra Hox repertoire reveals tailor-made Hox-code for Cnidarians. AB - Hox and ParaHox genes play decisive roles in patterning the anterior-posterior body axis in Bilateria. Evolutionary origin of Hox genes and primary body axis predate the divergence of Bilateria and Cnidaria. However, function of Cnidarian Hox-like genes and their regulation in axis determination is obscure due to studies limited to a few representative model systems. Present investigation is conducted using Hydra, a Hydrozoan member of phylum Cnidaria, to gain insights into the roles of Cnidarian Hox-like genes in primary axis formation. Here, we report identification of six Hox-like genes from our in-house transcriptome data. Phylogenetic analysis of these genes shows bilaterian counterparts of Hox1, Gsx and Mox. Additionally, we report CnoxB_HVUL, CnoxC2_HVUL and CnoxC3_HVUL belonging to two Cnidarian specific groups. In situ hybridization analysis of Hydra homologues provided important clues about their possible roles in pattern formation of polyps and bud development. Specifically, Hox1_HVUL is regulated by Wnt signaling and plays critical role in head formation. Collating information about expression patterns of different Hox-like genes from previous reports and this study reveals no conformity within Cnidaria. Indicating that unlike in Bilateria, there is no consolidated Hox-code determining primary body axis in Cnidaria. PMID- 26278346 TI - Measurement of spatial distribution of neutrons and gamma rays for BNCT using multi-imaging plate system. AB - Quality assurance of the spatial distributions of neutrons and gamma rays was tried using imaging plates (IPs) and converters to enhance the beam components in the epithermal neutron mode of the Kyoto University Reactor. The converters used were 4mm thick epoxy resin with B4C at 6.85 weight-percent (wt%) (10)B for epithermal neutrons, and 3mm thick carbon for gamma rays. Results suggested that the IP signal does not need a sensitivity correction regardless of the incident radiation that produces it. PMID- 26278347 TI - Design of photon converter and photoneutron target for High power electron accelerator based BNCT. AB - An electron accelerator, ILU-14, with current of 10 mA and 100 kW in power has been considered as one of the options for neutron source in Boron Neutron Capture Therapy (BNCT). The final design of neutron target has been obtained using MCNPX to optimize the neutron production. Tungsten in strip shape and D2O in cylindrical form have been proposed as the photon converter and the photoneutron target, respectively. In addition calculation of heat deposition in the photon target design has been considered to ensure mechanical stability of target. The results show that about 8.37*10(12) photoneutron/s with average energy of 615 keV can be produced by this neutron source design. In addition, using an appropriate beam shaping assembly an epithermal neutron flux of the order of 1.24*10(8) cm( 2) s(-1) can be obtained for BNCT applications. PMID- 26278348 TI - Potential of boron neutron capture therapy (BNCT) for malignant peripheral nerve sheath tumors (MPNST). AB - Malignant peripheral nerve sheath tumors (MPNST) are relatively rare neoplasms with poor prognosis. At present there is no effective treatment for MPNST other than surgical resection. Nonetheless, the anti-tumor effect of boron neutron capture therapy (BNCT) was recently demonstrated in two patients with MPNST. Subsequently, tumor-bearing nude mice subcutaneously transplanted with a human MPNST cell line were injected with p-borono-L-phenylalanine (L-BPA) and subjected to BNCT. Pathological studies then revealed that the MPNST cells were selectively destroyed by BNCT. PMID- 26278349 TI - BNCT treatment planning for superficial and deep-seated tumors: Experience from clinical trial of recurrent head and neck cancer at THOR. AB - Under the collaboration between National Tsing Hua University and Taipei Veterans General Hospital, clinical trial of recurrent head-and-neck cancer by Boron neutron capture therapy at Tsing Hua open-pool reactor started on August 11, 2010. Up to January 2014, 17 patients were treated. Based on the treatment planning experiences of clinical trials using in-house designed THORplan, different setups should be used for superficial and deep-seated tumors. Superficial tumor treatment gains benefits from the use of patient collimator, while direct irradiation is a better choice for deep-seated tumor. PMID- 26278350 TI - Country of birth modifies the association of fatty liver index with insulin action in Middle Eastern immigrants to Sweden. AB - AIMS: Non-alcohol fatty liver disease (NAFLD) is a strong risk factor for insulin resistance and type 2 diabetes. The prevalence of NAFLD varies across populations of different ethnic backgrounds but the prevalence in Middle Eastern populations, which are at high risk of type 2 diabetes, is largely unknown. Using fatty liver index (FLI) as a proxy for NAFLD the aim was to calculate the odds of NAFLD (FLI>=70) given country of origin and further to investigate the associations between ISI and FLI. METHODS: In 2010-2012 we conducted a population-based study of individuals aged 30-75 years born in Iraq or Sweden, in whom anthropometrics, fasting blood samples and oral glucose tolerance tests were performed and sociodemography and lifestyle behaviors characterized. RESULTS: A higher proportion of Iraqis (N=1085) than Swedes (N=605) had a high probability of NAFLD (FLI>=70, 32.5 vs. 22.6%, p<0.001, age- and sex-adjusted data) and ISI was more severely impaired (70.7 vs. 95.9%, p<0.001). Independently of traditional risk factors for NAFLD, being born in Iraqi increased the risk of FLI>=70 (OR 1.59: 95% CI 1.15, 2.20). Furthermore, country of birth presented a stronger association between ISI and FLI>=70 in Iraqis than in Swedes (P(interaction)=0.019). CONCLUSIONS: Our data indicate that immigrants from Iraq are at higher risk of NAFLD. The finding that country of birth modifies the relationship of FLI with ISI, suggests that liver fat may be a stronger determinant of impaired insulin action and increased risk of type 2 diabetes in Iraqis than in Swedes. PMID- 26278351 TI - Breastfeeding practices that support women with diabetes to breastfeed. AB - The aim of this literature review was to identify breastfeeding practices that support women with diabetes to breastfeed. A search was undertaken of CINAHL and Medline databases to identify studies that inform breastfeeding practice for women with diabetes. This resulted in 14 studies (19 records). Most studies focused on women with GDM and T1D with some consideration of T2D. The review has been organised using Maslow's Hierarchy of Needs, to enable a clear focus on the needs of women while identifying supportive practices. The key findings of this review are that breastfeeding as the first feed and exclusive breastfeeding are beneficial to meeting physiological needs. Preparations such as having food nearby and having someone to call on can help meet the woman's safety and security needs. A sense of love and belonging is supported by the practice of an early first breastfeed, but antenatal breast milk expression is currently not recommended. The woman's self-esteem can be enhanced through informed multidisciplinary support. Finally, self-actualisation or success with breastfeeding has been achieved by women with diabetes. Common breastfeeding concerns rather than diabetes have been identified as reasons for cessation of breastfeeding. Practices that support women deal with these concerns are recommended. PMID- 26278352 TI - Multi-locus genotyping reveals absence of genetic structure in field populations of the brown ear tick (Rhipicephalus appendiculatus) in Kenya. AB - Rhipicephalus appendiculatus is an important tick vector of several pathogens and parasitizes domestic and wild animals across eastern and southern Africa. However, its inherent genetic variation and population structure is poorly understood. To investigate whether mammalian host species, geographic separation and resulting reproductive isolation, or a combination of these, define the genetic structure of R. appendiculatus, we analyzed multi-locus genotype data from 392 individuals from 10 geographic locations in Kenya generated in an earlier study. These ticks were associated with three types of mammalian host situations; (1) cattle grazing systems, (2) cattle and wildlife co-grazing systems (3) wildlife grazing systems without livestock. We also analyzed data from 460 individuals from 10 populations maintained as closed laboratory stocks and 117 individuals from five other species in the genus Rhipicephalus. The pattern of genotypes observed indicated low levels of genetic differentiation between the ten field populations (FST=0.014+/-0.002) and a lack of genetic divergence corresponding to the degree of separation of the geographic sampling locations. There was also no clear association of particular tick genotypes with specific host species. This is consistent with tick dispersal over large geographic ranges and lack of host specificity. In contrast, the 10 laboratory populations (FST=0.248+/-0.015) and the five other species of Rhipicephalus (FST=0.368+/-0.032) were strongly differentiated into distinct genetic groups. Some laboratory bred populations diverged markedly from their field counterparts in spite of originally being sampled from the same geographic locations. Our results demonstrate a lack of defined population genetic differentiation in field populations of the generalist R. appendiculatus in Kenya, which may be a result of the frequent anthropogenic movement of livestock and mobility of its several wildlife hosts between different locations. PMID- 26278353 TI - The busulfan metabolite EdAG irreversibly glutathionylates glutaredoxins. AB - The DNA alkylating agent busulfan is used to 'precondition' patients with leukemia, lymphomas and other hematological disorders prior to hematopoietic stem cell transplants. Busulfan is metabolized via conjugation with glutathione (GSH) followed by intramolecular rearrangement to the GSH analog gamma-glutamyl dehydroalanyl -glycine (EdAG). EdAG contains the electrophilic dehydroalanine, which is expected to react with protein nucleophiles, particularly proteins with GSH binding sites such as glutaredoxins (Grx's). Incubation of EdAG with human Grx-1 or Grx-2 results in facile adduction of cys-23 and cys-77, respectively, as determined by ESI-MS/MS. The resulting modified proteins are catalytically inactive. In contrast, the glutathione transferase A1-1 includes a GSH binding site with a potentially reactive tyrosinate (Tyr-9) but it does not react with EdAG. Similarly, Cys-112 of GSTA1-1, which lies outside the active site and is known to form disulfides with GSH, does not react with EdAG. The results provide the first demonstration of the reactivity of any busulfan metabolites with intact proteins, and they suggest that GSH-binding sites containing thiolates are most susceptible. The adduction of Grx's by EdAG suggests the possible alteration of proteins that are normally regulated via Grx-dependent reversible glutathionylation or deglutathionylation. Dysregulation of Grx-dependent processes could contribute to cellular toxicity of busulfan. PMID- 26278354 TI - A Taiji-principle-designed magnetic porous C-doped graphitic carbon nitride for environment-friendly solid phase extraction of pollutants from water samples. AB - A new magnetic porous carbon-doped graphitic carbon nitride nanocomposite and experimental strategies were environment-friendly designed for solid phase extraction of brominated flame retardants from water sample. The easily synthesized and low cost nanocomposite was characterized using techniques, including Fourier transform infrared spectroscopy, X-ray diffraction spectrometry, elemental analysis, and transmission electron microscopy. The large surface area and enhanced interactions of this nanocomposite with its adsorption behavior in Taiji principle (a balance of hydrophilicity and hydrophobicity) in aqueous phase benefit the extraction. Magnetic solid phase extraction has advantages such as low solvent consumption and reusability of the sorbent, and was therefore employed in this study. In addition, a quicker and less laborious statistical method, known as response surface methodology, was used to investigate and optimize some crucial factors that affected the adsorption. The combined use of this new nanocomposite and experimental strategy showed excellent precision (2.7-5.2%) and sensitivity (limits of detection (S/N=3): 0.1-0.2 MUg L( 1)). This method was successfully applied to the analysis of real water samples giving good spiked recoveries over the range of 92.4-99.8%. This research provides an environment-friendly strategy to prepare suitable sorbents for extraction or adsorption of various compounds within different matrices. PMID- 26278355 TI - Characterization of post-translationally modified peptides by hydrophilic interaction and reverse phase liquid chromatography coupled to quadrupole-time-of flight mass spectrometry. AB - This work explores the use of both hydrophilic interaction liquid chromatography (HILIC) and reverse phase liquid chromatography (RPLC) for the separation and subsequent characterization of bovine caseinomacropeptide (CMP) phosphopeptides and O-glycopeptides using a quadrupole-time-of-flight (QTOF) mass spectrometer with electrospray ionization. Two neutral, ethylene bridged hybrid (BEH) amide and polyhydroxyethyl aspartamide (PHEA), and a zwitterionic, sulfobetaine (ZIC), stationary phases were used for the HILIC mode, whilst an octadecylsilane (C18) stationary phase was employed for the RPLC separation. Overall, developed HILIC QTOF method using the ZIC or BEH amide stationary phases resulted to be the most efficient methods to separate and characterize post-translationally modified (PTM) peptides without the need of any previous fractionation or derivatization step. The separation of phosphopeptides and differently sialylated O glycopeptides in the ZIC stationary phase was dominated by an electrostatic repulsion interaction mechanism between the negatively charged phosphate groups or sialic acid moieties and the negatively charged terminal sulfonate group of the stationary phase, whereas the separation of either non-modified peptides or neutral O-glycopeptides both free of basic amino acids was based on a partitioning mechanism. In neutral amide columns, the separation was mainly dominated by hydrophilic partitioning, leading to a higher retention of the post translationally modified peptides than the unmodified counterparts due to the hydrophilicity provided by the phosphate groups and/or O-glycans. As a consequence, HILIC-ESI-QTOF MS operating in the positive ion mode is a powerful tool for the characterization of underivatized O-glycopeptides and phosphopeptides. PMID- 26278356 TI - An attempt to estimate ionic interactions with phenyl and pentafluorophenyl stationary phases in supercritical fluid chromatography. AB - Pentafluorophenyl-bonded silica (PFP) phases employed in high-performance liquid chromatography (HPLC) often provide very different results depending on the column manufacturer. PFP phases also provide significantly different selectivity from non-fluorinated aromatic phases. As all HPLC columns can also be employed with carbon dioxide-based mobile phases, PFP phases can also be useful to supercritical fluid chromatography (SFC). However, whether they provide adequate retention and selectivity in SFC conditions is necessary for them to find applicability with this technique. In our laboratory, a column classification for packed column SFC was designed, based on the solvation parameter model, which currently comprises data for about eighty different columns. In this paper, we present the characterization of eleven PFP phases provided by different manufacturers used with carbon dioxide-methanol mobile phases. The columns are compared to fifteen other non-fluorinated phenyl and diphenyl phases in terms of their retention and separation characteristics assessed by the solvation parameter model with five Abraham descriptors. The latter is insufficient for an accurate description of retention mechanisms on the PFP phases, thus two extra terms accounting for ionic interactions with anions and cations (D(-) and D(+)), previously developed for HPLC in hydrophilic interaction mode (HILIC), are introduced. While some approximations are necessary regarding the true pH and pKa values in CO2-based mobile phases, the retention models are significantly improved by this addition, allowing to integrate ionizable analytes in the test set for evaluation of ionic interactions in the chromatographic systems. PMID- 26278357 TI - Coextraction of acidic, basic and amphiprotic pollutants using multiwalled carbon nanotubes/magnetite nanoparticles@polypyrrole composite. AB - The simultaneous extraction of acidic, basic and amphiprotic pollutants from various samples is a considerable and disputable concept in sample preparation strategies. In this study, for the first time, coextraction of acidic, basic and amphiprotic pollutants (polar and apolar) with multiwalled carbon nanotubes/Fe3O4@polypyrrole (MWCNTs/Fe3O4@PPy) composite based dispersive micro solid phase extraction followed by high performance liquid chromatography-photo diode array detection was introduced. Firstly, the extraction efficiency of various magnetic nanosorbents including Fe3O4, MWCNTs/Fe3O4, graphene oxide/Fe3O4 (GO/Fe3O4), Fe3O4@PPy, MWCNTs/Fe3O4@PPy and GO/Fe3O4@PPy were compared. The results revealed that MWCNTs/Fe3O4@PPy nanocomposite has higher extraction efficiency for five selected model analytes (4-nitrophenol, 3-nitroaniline, 2,4 dichloroaniline, 3,4-dichloroaniline and 1-amino-2-naphthol). Box-Behnken design methodology combined with desirability function approach was applied to find out the optimal experimental conditions. The opted conditions were: pH of the sample, 8.2; sorbent amount, 12 mg; sorption time, 5.5 min; salt concentration, 14% w/w; type and volume of the eluent, 120 MUL acetonitrile; elution time; 2 min. Under the optimum conditions detection limits and linear dynamic ranges were achieved in the range of 0.1-0.25 MUg L(-1) and 0.5-600 MUg L(-1), respectively. The percent of extraction recovery and relative standard deviations (n=5) were in the range of 45.6-82.2 and 4.0-8.5, respectively. Ultimately, the applicability of this method was successfully confirmed by analyzing rain, snow and river water samples and satisfactory results were obtained. PMID- 26278358 TI - Centrifugal partition chromatography in a biorefinery context: Separation of monosaccharides from hydrolysed sugar beet pulp. AB - A critical step in the bioprocessing of sustainable biomass feedstocks, such as sugar beet pulp (SBP), is the isolation of the component sugars from the hydrolysed polysaccharides. This facilitates their subsequent conversion into higher value chemicals and pharmaceutical intermediates. Separation methodologies such as centrifugal partition chromatography (CPC) offer an alternative to traditional resin-based chromatographic techniques for multicomponent sugar separations. Highly polar two-phase systems containing ethanol and aqueous ammonium sulphate are examined here for the separation of monosaccharides present in hydrolysed SBP pectin: l-rhamnose, l-arabinose, d-galactose and d-galacturonic acid. Dimethyl sulfoxide (DMSO) was selected as an effective phase system modifier improving monosaccharide separation. The best phase system identified was ethanol:DMSO:aqueous ammonium sulphate (300gL(-1)) (0.8:0.1:1.8, v:v:v) which enabled separation of the SBP monosaccharides by CPC (200mL column) in ascending mode (upper phase as mobile phase) with a mobile phase flow rate of 8mLmin(-1). A mixture containing all four monosaccharides (1.08g total sugars) in the proportions found in hydrolysed SBP was separated into three main fractions; a pure l-rhamnose fraction (>90%), a mixed l-arabinose/d-galactose fraction and a pure d-galacturonic acid fraction (>90%). The separation took less than 2h demonstrating that CPC is a promising technique for the separation of these sugars with potential for application within an integrated, whole crop biorefinery. PMID- 26278359 TI - Comprehensive two-dimensional gas chromatography with pattern modulation. AB - Comprehensive two-dimensional gas chromatography (GC*GC) modulators normally transfer primary column effluent to the head of the secondary column as a series of sharp pulses. Such pulses are produced with time-varying temperature gradients in thermal modulation or with time-varying flow patterns in flow modulation. Thermal modulators produce narrow peaks at optimal flow rates, but require large amounts of consumables or a highly engineered heating/cooling system. Flow modulators involve simpler hardware and no additional consumables. However, flow modulators require a large increase in secondary column flow or transfer only a small portion of the primary effluent to the secondary column. This study examines a new method of producing GC*GC separations with a flow modulator. Instead of injecting narrow pulses, the modulator transfers primary effluent to the secondary column in the form of an intricate injection pattern. The detector signal is deconvoluted and converted to a two-dimensional chromatogram. The high duty cycle of the technique (>50%) leads to deconvoluted peaks with twenty times greater intensity than those produced by conventional modulation with a Deans switch modulator. Pattern modulation can be produced without requiring elevated carrier flows. This study evaluates the efficacy of pattern modulation GC*GC by analyzing a standard mixture of 43 oxygenated organic compounds and an E85 fuel sample. PMID- 26278360 TI - Gas chromatographic separation of stereoisomers of non-protein amino acids on modified gamma-cyclodextrin stationary phase. AB - Stereoisomers (enantiomers and diastereoisomers) of synthetic, non-protein amino acids comprising alpha-, beta-, and gamma-amino acids, including alpha,alpha dialkyl amino acids, were converted into the respective N-trifluoroacetyl-O methyl esters and analyzed and resolved by gas chromatography (GC) on a commercial fused silica capillary column coated with the chiral stationary phase octakis(3-O-butyryl-2,6-di-O-pentyl)-gamma-cyclodextrin. This column is marketed under the trade name Lipodex((r)) E. Chromatograms, retention times, and a chart displaying the retention times of approximately 40 stereoisomers of amino acids are presented. With few exceptions, baseline or almost baseline resolution was achieved for enantiomers and diastereoisomers. The chromatographic method presented is considered to be highly suitable for the elucidation of the stereochemistry of non-protein amino acids, for example in natural products, and for evaluating the enantiopurity of genetically non-coded amino acids used for the synthesis and design of conformationally tailored peptides. The method is applicable to extraterrestrial materials or can be used in experimental work related to abiotic syntheses or enantioselective destruction and amplification of amino acids. PMID- 26278361 TI - A two level hierarchical model of protein retention in ion exchange chromatography. AB - Predicting protein retention in ion exchange chromatography (IEX) from first principles is a fascinating perspective. In this work a two level hierarchical modeling strategy is proposed in order to calculate protein retention factors. Model predictions are tested against experimental data measured for Lysozyme and Chymotrypsinogen A in IEX columns as a function of ionic strength and pH. At the highest level of accuracy Molecular Dynamics (MD) simulations in explicit water are used to determine the interaction free energy between each of the two proteins and the IEX stationary phase for a reference pH and ionic strength. At a lower level of accuracy a linear response model based on an implicit treatment of solvation and adopting a static protein structure is used to calculate interaction free energies for the full range of pHs and ionic strengths considered. A scaling coefficient, determined comparing MD and implicit solvent simulations, is then introduced in order to correct the linear response model for errors induced by the adoption of a static protein structure. The calculated free energies are then used to compute protein retention factors, which can be directly compared with experimental data. The possibility to introduce a third level of accuracy is explored testing the predictions of a semiempirical model. A quantitative agreement between the predicted and measured protein retention factors is obtained using the coupled MD-linear response models, supporting the reliability of the proposed approach. The model allows quantifying the electrostatic, van der Waals, and conformational contributions to the interaction free energies. A good agreement between experiments and model is obtained also using the semiempirical model that, although requiring parameterization over higher level models or experimental data, proves to be useful in order to rapidly determine protein retention factors across wide pH and ionic strength ranges as it is computationally inexpensive. PMID- 26278362 TI - Underuse and underreporting of smoking cessation for smokers with a new urologic cancer diagnosis. AB - BACKGROUND: Urothelial carcinoma of the bladder (UCB) or upper urinary tract (UCUT) and renal cell carcinoma (RCC) are smoking-related genitourinary (GU) malignancies. A new diagnosis of smoking-related GU cancer is an opportunity when smoking cessation interventions may have increased effectiveness. Underuse or underreporting of cessation tools in this setting represents potential for quality improvement. We estimated the use of smoking cessation in new smoking related GU cancer visits based on billing claims. METHODS: From MarketScan data, over 34 million enrollees aged 18 to 65 years, calendar years 2007 to 2011, were screened for billing codes for index UCB/UCUT or RCC and tobacco use disorder. Qualifying individuals were assessed for claims-based pharmacologic or counseling smoking cessation interventions in the 12 months following diagnosis using Current Procedural Terminology (CPT) codes and International Classification of Diseases Ninth Revision (ICD-9) codes. Multivariable logistic regression identified factors associated with smoking cessation intervention. RESULTS: From over 111,453 incident cancers, 5,777 smokers with tobacco-related GU malignancy were identified by billing claims (40% UCB, 46% RCC, 4.2% UCUT, and 9.8% multiple cancers). Claims for intervention were rare (5.3%). Among intervention recipients, 240 (80%) had UCB and 92% had claims for either counseling or medications, only 8% had both. Most claims-based interventions (61%) were within 3 months after GU cancer diagnosis. On multivariable analysis UCB was associated increased odds of claims-based intervention (odds ratio [OR] = 6.27; 95% CI: 4.57 8.60) compared with UCUT and RCC. Other significant factors included more comorbidities (Charlson score = 1, OR = 1.50, 95% CI: 1.06-2.13; Charlson score>=2, OR = 1.89, 95% CI: 1.19-3.02 compared with Charlson score = 0) and diagnosis in the latter half of the study period (OR = 1.30, 95% CI: 1.02-1.67 compared with earlier years). CONCLUSIONS: Although a new diagnosis of a smoking related GU malignancy diagnosis offers greater opportunity for provider-driven smoking cessation, timely multimodal claims-based cessation interventions are underreported or underused. PMID- 26278363 TI - Risk for Clostridium difficile infection after radical cystectomy for bladder cancer: Analysis of a contemporary series. AB - INTRODUCTION: This study seeks to evaluate the incidence and associated risk factors of Clostridium difficile infection (CDI) in patients undergoing radical cystectomy (RC) for bladder cancer. METHODS: We retrospectively reviewed a single institution's bladder cancer database including all patients who underwent RC between 2010 and 2013. CDI was diagnosed by detection of Clostridium difficile toxin B gene using polymerase chain reaction-based stool assay in patients with clinically significant diarrhea within 90 days of the index operation. A multivariable logistic regression model was used to identify demographics and perioperative factors associated with developing CDI. RESULTS: Of the 552 patients who underwent RC, postoperative CDI occurred in 49 patients (8.8%) with a median time to diagnosis after RC of 7 days (interquartile range: 5-19). Of the 122 readmissions for postoperative complications, 10% (n = 12) were related to CDI; 2 patients died of sepsis directly related to severe CDI. On multivariate logistic regression, the use of chronic antacid therapy (odds ratio = 1.9, 95% CI: 1.02-3.68, P = 0.04) and antibiotic exposure greater than 7 days (odds ratio = 2.2, 95% CI: 1.11-4.44, P = 0.02) were independently associated with developing CDI. The use of preoperative antibiotics for positive findings on urine culture within 30 days before surgery was not statistically significantly associated with development of CDI (P = 0.06). CONCLUSIONS: The development of CDI occurs in 8.8% of patients undergoing RC. Our study demonstrates that use of chronic antacid therapy and long duration of antimicrobial exposure are associated with development of CDI. Efforts focusing on minimizing antibiotic exposure in patients undergoing RC are needed, and perioperative antimicrobial prophylaxis guidelines should be followed. PMID- 26278364 TI - Renal function in patients with Wilms tumor. AB - Survival in patients with Wilms tumor (WT) is excellent compared with other pediatric malignancies and adult renal tumors. Treatment-related long-term morbidity and mortality in WT survivors is an area of increasing concern. Renal dysfunction is an example of one of the most feared long-term issues observed in these survivors. Direct toxicity from chemotherapy and radiation as well as direct nephron ablation from surgical treatment (nephrectomy) renders the kidney susceptible to a multitude of problems over time in patients with WT. In this article, we review the existing literature pertaining to renal function in these patients. Incidence rates, causes, and methods to mitigate renal dysfunction are presented in 3 distinct clinical situations: sporadic unilateral WT, syndromic unilateral WT, and bilateral WT. We also offer a critical lens on the current role of nephron-sparing surgery as a means to preserve renal function in these patients. Finally, we discuss potential avenues for refining renal function preservation in patients with WT in the future. We conclude that: (1) renal function in pediatric cancer survivors must be carefully ascertained prospectively using methods that allow diagnosis of mild cases (rather than focus solely on extreme cases represented by the development of end-stage renal disease), (2) every effort should be made to recognize subtle features of predisposition syndromes to avoid syndromic cases from being misclassified and treated as sporadic, (3) molecular stratification for disease aggressiveness as well as multifocality and renal dysfunction will be very important to tailor treatment and balance survival with preservation of renal function, and (4) the role and potential benefits of nephron-sparing surgery deserves careful exploration under well-designed protocols. PMID- 26278365 TI - Urothelial carcinoma with squamous differentiation: response to chemotherapy and radiation. AB - PURPOSE: This review will summarize the literature relating urothelial carcinoma with squamous differentiation and its response to chemotherapy or radiation therapy. METHODS: The English literature in PubMED was extensively search for articles pertaining to urothelial carcinoma with squamous differentiation and its response to chemotherapy or radiation. Articles reference lists were then further scrutinized to ensure all relevant literature had been identified. RESULTS: Urothelial carcinoma with squamous differentiation is generally treated as if it were pure urothelial carcinoma. However, it remains unclear if such mixed histology portends a different prognosis for patients with bladder cancer, particularly regarding the response to chemotherapy and radiation. Initial studies suggested a worse response to such therapy in mixed histology but more recent data has challenged that observation. Unfortunately the literature is limited by the type and quality of the existent studies and mixed results among the data that is available. CONCLUSION: The final word on whether urothelial carcinoma with squamous differentiation responds differently to chemotherapy or radiation therapy remains uncertain. This important question warrants careful study in the future. PMID- 26278366 TI - Waist circumference, waist-hip ratio, body mass index, and prostate cancer risk: results from the North-American case-control study Prostate Cancer & Environment Study. AB - INTRODUCTION: The evidence on the association between anthropometric measures quantifying body fatness and prostate cancer (PCa) risk is not entirely consistent. Associations among waist circumference (WC), waist-hip ratio, body mass index (BMI), and PCa risk were assessed in a population-based case-control study. PATIENTS AND METHODS: The study included 1933 incident PCa cases diagnosed between 2005 and 2009. Population controls were 1994 age-matched (+/-5y) Montreal residents selected from electoral lists. Information on sociodemographics, medical history including PCa screening, height, weight, and waist and hip circumferences was collected through interviews. Logistic regression was used to assess odds ratios (ORs) for the association between anthropometric measures, and overall and grade-specific PCa. RESULTS: After adjustment for BMI, an excess risk of high-grade PCa (Gleason>=7) was associated with a WC >=102cm (OR = 1.47 [1.22 1.78]) and with a waist-hip ratio >1.0 (OR = 1.20 [1.01-1.43]). Men with a BMI>=30kg/m(2) had a lower risk of PCa, regardless of grade. Restricting to subjects recently screened for PCa did not alter findings. CONCLUSION: Elevated BMI was associated with a lower risk of PCa, regardless of grade. Contrastingly, abdominal obesity, when adjusted for BMI, yielded results in the opposite direction. Taken together, our observations suggest that the specific body fat distribution (abdominal), for a given BMI, is a predictor of PCa risk, whereas BMI alone is not. BMI and abdominal obesity, especially when measured by the WC, should be examined conjointly in future studies on this issue and may require consideration at patient counseling. PMID- 26278369 TI - Challenges and opportunities of the International League of Associations for Rheumatology (ILAR). PMID- 26278368 TI - An additional cysteine in a typical 2-Cys peroxiredoxin of Pseudomonas promotes functional switching between peroxidase and molecular chaperone. AB - Peroxiredoxins (Prx) have received considerable attention during recent years. This study demonstrates that two typical Pseudomonas-derived 2-Cys Prx proteins, PpPrx and PaPrx can alternatively function as a peroxidase and chaperone. The amino acid sequences of these two Prx proteins exhibit 93% homology, but PpPrx possesses an additional cysteine residue, Cys112, instead of the alanine found in PaPrx. PpPrx predominates with a high molecular weight (HMW) complex and chaperone activity, whereas PaPrx has mainly low molecular weight (LMW) structures and peroxidase activity. Mass spectrometry and structural analyses showed the involvement of Cys112 in the formation of an inter-disulfide bond, the instability of LMW structures, the formation of HMW complexes, and increased hydrophobicity leading to functional switching of Prx proteins between peroxidase and chaperone. PMID- 26278370 TI - Co-combustion of tannery sludge in a commercial circulating fluidized bed boiler. AB - Co-combusting hazardous wastes in existing fluidized bed combustors is an alternative to hazardous waste treatment facilities, in shortage in China. Tannery sludge is a kind of hazardous waste, considered fit for co-combusting with coal in fluidized bedboilers. In this work, co-combustion tests of tannery sludge and bituminous coal were conducted in a power plant in Jiaxing, Zhejiang province. Before that, the combustion behavior of tannery sludge and bituminous were studied by thermogravimetric analysis. Tannery sludge presented higher reactivity than bituminous coal. During the co-combustion tests, the emissions of harmful gases were monitored. The results showed that the pollutant emissions met the Chinese standard except for NOx. The Concentrations of seven trace elements (As, Cr, Cd, Ni, Cu, Pb, Mn) in three exit ash flows (bottom ash in bed, fly ash in filter, and submicrometer aerosol in flue gas) were analyzed. The results of mono-combustion of bituminous coal were compared with those of co-combustion with tannery sludge. It was found that chromium enriched in fly ash. At last, the leachability of fly ash and bottom ash was analyzed. The results showed that most species were almost equal to or below the limits except for As in bottom ashes and Cr in the fly ash of co-combustion test. The concentrations of Cr in leachates of co-combustion ashes are markedly higher than that of coal mono combustion ashes. PMID- 26278371 TI - Recovery of glass from the inert fraction refused by MBT plants in a pilot plant. AB - Selective collection is a common practice in many countries. However, even in some of those countries there are recyclable materials, like packaging glass, erroneously deposited in the Mixed Municipal Solid Waste (MMSW). In the present paper, a solution is proposed to recover glass from the inert reject of Mechanical and Biological Treatment (MBT) plants treating MMSW aiming at its recycling. The inert reject of MBT (MBTr) plants is characterized by its small particle size and high heterogeneity. The study was made with three real samples of diverse characteristics superimposed mainly by the different upstream MBT. One of the samples (VN) had a high content in organics (approximately 50%) and a particle size smaller than 16 mm. The other two were coarser and exhibited similar particle size distribution but one (RE) was rich in glass (almost 70%) while the other (SD) contained about 40% in glass. A flowsheet was developed integrating drying, to eliminate moisture related with organic matter contamination; magnetic separation, to separate remaining small ferrous particles; vacuum suction, to eliminate light materials; screening, to eliminate the finer fraction that has a insignificant content in glass, and to classify the >6mm fraction in 6-16 mm and >16 mm fractions to be processed separately; separation by particle shape, in the RecGlass equipment specifically designed to eliminate stones; and optical sorting, to eliminate opaque materials. A pilot plant was built and the tests were conducted with the three samples separately. With all samples, it was possible to attain approximately 99% content in glass in the glass products, but the recovery of glass was related with the feed particle size. The finer the feed was, the lower the percentage of glass recovered in the glass product. The results show that each one of the separation processes was needed for product enrichment. The organic matter recovered in the glass product was high, ranging from 0.76% to 1.13%, showing that drying was not sufficient in the tests but that it is a key process for the success of the operation. PMID- 26278372 TI - Predictive models and airflow distribution associated with the zone of influence (ZOI) during air sparging remediation. AB - Laboratory two-dimensional airflow visualisation model tests were conducted to assess the effect of particle size and air injection pressure on airflow patterns, physical characteristics of the zone of influence (ZOI) and the airflow rate distribution within the ZOI. The results indicate that the pattern transitions from chamber flow to channelized flow and then to bubbly flow occurred at effective particle sizes (D10) in the ranges 0.22-0.42 mm and 1.42 2.1mm, respectively. The ZOI is shaped like a conical frustum, and there exists a "stable ZOI" for each type of porous medium in channelised and bubbly flow during sparging tests. A formula for calculating the size of the ZOI radius was established based on the conical frustum-shaped results and the "stable ZOI", and comparing the calculated results with field data demonstrated that the formula has application value, except in large-scale heterogeneous aquifers. The distribution of the airflow rate within the ZOI, which is quite uneven, varies from the maximum rate (which occurred just above the sparger) to zero with the increase of the lateral distance from the sparger. Moreover, the airflow distribution can be fitted using a unified dimensionless Gaussian function under different sparging pressures for a given porous medium. All of the results described above provide valuable information for the design and theoretical modelling of air sparging for groundwater remediation. PMID- 26278367 TI - Genetic and Epigenetic Diversities Shed Light on Domestication of Cultivated Ginseng (Panax ginseng). AB - Chinese ginseng (Panax ginseng) is a medically important herb within Panax and has crucial cultural values in East Asia. As the symbol of traditional Chinese medicine, Chinese ginseng has been used as a herbal remedy to restore stamina and capacity in East Asia for thousands of years. To address the evolutionary origin and domestication history of cultivated ginseng, we employed multiple molecular approaches to investigate the genetic structures of cultivated and wild ginseng across their distribution ranges in northeastern Asia. Phylogenetic and population genetic analyses revealed that the four cultivated ginseng landraces, COMMON, BIANTIAO, SHIZHU, and GAOLI (also known as Korean ginseng), were not domesticated independently and Fusong Town is likely one of the primary domestication centers. In addition, our results from population genetic and epigenetic analyses demonstrated that cultivated ginseng maintained high levels of genetic and epigenetic diversity, but showed distinct cytosine methylation patterns compared with wild ginseng. The patterns of genetic and epigenetic variation revealed by this study have shed light on the domestication history of cultivated ginseng, which may serve as a framework for future genetic improvements. PMID- 26278373 TI - Trace elements in particulate matter from metropolitan regions of Northern China: Sources, concentrations and size distributions. AB - Public concerns over airborne trace elements (TEs) in metropolitan areas are increasing, but long-term and multi-site observations of size-resolved aerosol TEs in China are still lacking. Here, we identify highly elevated levels of atmospheric TEs in megacities and industrial sites in a Beijing-Tianjin-Hebei urban agglomeration relative to background areas, with the annual mean values of As, Pb, Ni, Cd and Mn exceeding the acceptable limits of the World Health Organization. Despite the spatial variability in concentrations, the size distribution pattern of each trace element was quite similar across the region. Crustal elements of Al and Fe were mainly found in coarse particles (2.1-9 MUm), whereas the main fraction of toxic metals, such as Cu, Zn, As, Se, Cd and Pb, was found in submicron particles (<1.1 MUm). These toxic metals were enriched by over 100-fold relative to the Earth's crust. The size distributions of Na, Mg, K, Ca, V, Cr, Mn, Ni, Mo and Ba were bimodal, with two peaks at 0.43-0.65 MUm and 4.7 5.8 MUm. The combination of the size distribution information, principal component analysis and air mass back trajectory model offered a robust technique for distinguishing the main sources for airborne TEs, e.g., soil dust, fossil fuel combustion and industrial emissions, at different sites. In addition, higher elemental concentrations coincided with westerly flow, indicating that polluted soil and fugitive dust were major sources of TEs on the regional scale. However, the contribution of coal burning, iron industry/oil combustion and non-ferrous smelters to atmospheric metal pollution in Northern China should be given more attention. Considering that the concentrations of heavy metals associated with fine particles in the target region were significantly higher than those in other Asian sites, the implementations of strict environmental standards in China are required to reduce the amounts of these hazardous pollutants released into the atmosphere. PMID- 26278374 TI - Dynamics and sources of reduced sulfur, humic substances and dissolved organic carbon in a temperate river system affected by agricultural practices. AB - Although reduced organic sulfur substances (RSS) as well as humic substances (HS) are widely suspected to play a role in, for example, metal speciation or used as a model of dissolved organic carbon (DOC) in laboratory studies, reports of their quantification in natural waters are scarce. We have examined the dynamics and sources of reduced sulfur, HS and DOC over an annual cycle in a river system affected by agricultural practices. The new differential pulse cathodic stripping voltammetry was successfully applied to measure glutathione-like compounds (GSHs), thioacetamide-like compounds (TAs) and the liquid chromatography coupled to organic detector to analyze HS and DOC at high frequency in the Penze River (NW France). The streamflow-concentration patterns, principal components analysis and flux analysis allowed discrimination of the source of each organic compound type. Surprisingly, the two RSS and HS detected in all samples, displayed different behavior. As previously shown, manuring practice is the main source of DOC and HS in this watershed where agricultural activity is predominant. The HS were then transferred to the river systems via runoff, particularly during the spring and autumn floods, which are responsible of >60% of the annual flux. TAs had a clear groundwater source and may be formed underground, whereas GSHs displayed two sources: one aquagenic in spring and summer probably linked to the primary productivity and a second, which may be related to bacterial degradation. High sampling frequency allowed a more accurate assessment of the flux values which were 280 tC y(-1) for DOC representing 20 kg C ha(-1) y(-1). HS, TAs and GSHs fluxes represented 60, 13, and 4% of the total annual DOC export, respectively. PMID- 26278375 TI - Alteration in the expression of antioxidant and detoxification genes in Chironomus riparius exposed to zinc oxide nanoparticles. AB - Zinc oxide nanoparticles (ZnONPs) are widely used in several commercial products due to their unique physicochemical properties. However, their release into the aquatic environments through various anthropogenic activities will lead to toxic effect in aquatic organisms. Although several investigations have been reported on the effect of ZnONPs in aquatic organisms using traditional end points such as survival, growth, and reproduction, the molecular level end points are faster and sensitive. In this study, the expression of different genes involved in oxidative stress response, detoxification, and cellular defense was studied in an ecotoxicologically important bio-monitoring organism Chironomus riparius in order to understand the subcellular effects of ZnONPs. The fourth instar larvae were exposed to 0, 0.2, 2, 10, and 20 mg/L of ZnONPs and Zn ions (in the form of ZnSO4.7H2O) for 24 and 48 h period. The expression of CuZn superoxide dismutase, manganese superoxide dismutase, catalase, phospholipid hydroperoxide glutathione peroxidase, thioredoxin reductase 1 and delta-3, sigma-4 and epsilon-1 classes of glutathione S-transferases, cytochrome p4509AT2, and heat shock protein 70 were studied using real-time polymerase chain reaction method. Gene expression results showed that the expression of genes related to oxidative stress response was more pronounced as a result of ZnONPs exposure as compared to Zn ions. The mRNA expression of genes involved in detoxification and cellular protection was also modulated. Significantly higher expression levels of oxidative stress-related genes shows that oxidative stress is an important mechanism of toxicity as a result of ZnONPs exposure in C. riparius. PMID- 26278376 TI - Polyphenolic Profile of Pear Leaves with Different Resistance to Pear Psylla (Cacopsylla pyri). AB - The European pear psylla, Cacopsylla pyri L. (Hemiptera: Psyllidae), is one of the most serious arthropod pests of pear. Since proper control of this pest is essential, better understanding of the complex plant-pest relationship is mandatory. This research deals with constitutive polyphenolic profiles in leaves of 22 pear cultivars of diverse origin (P. communis, P. pyrifolia, and P. pyrifolia * P. communis) and different resistance to psylla. The study was designed to show which differences in the polyphenolic profile of leaves from resistant and susceptible pear cultivars could be utilized as information in subsequent breeding programs. The results demonstrated that the leaves of Oriental pear cultivars contained much higher amounts of p-hydroxybenzoic acid, ferulic acid, aesculin, and naringin, that, together with detected 3-O-(6"-O-p coumaroyl)-hexoside, apigenin, apigenin 7-O-rutinoside, and hispidulin, indicated a clear difference between the species and might represent phenolics responsible for psylla resistance. PMID- 26278377 TI - Autonomic and sensory nerve modulation of peristalsis in the upper urinary tract. AB - The primary function of the upper urinary tract is to propel urine and various water-soluble toxic compounds from the kidneys to the bladder for storage and evacuation to maintain body ionic balance and contribute to the regulation of blood volume and pressure. The mechanism by which the upper urinary tract propels urine has long been considered to be myogenic in origin as peristaltic contractions in vivo and in vitro (pyeloureteric peristalsis) propagate in a manner little affected by drugs that block nerve conduction or the sympathetic and parasympathetic transmission. However, it is now well established that the release of intrinsic prostaglandins and neuropeptides from primary sensory nerves (PSNs) helps to maintain pyeloureteric peristalsis. Electrical field stimulation of PSNs evokes species-specific positive inotropic and chronotropic effects that have been attributed to release of excitatory tachykinins superimposed on negative inotropic and chronotropic effects associated with the release of calcitonin gene related peptide (CGRP), a rise in cellular cyclic-adenosine monophosphate (cAMP) and a protein kinase A-dependent activation of glibenclamide sensitive ATP-dependent K+ (KATP) channels. This review summarises the existing evidence of the nervous control of the upper urinary tract and recent evidence suggesting that the autonomic innervation may indirectly modulate pyeloureteric peristalsis via the activation of PSN nicotinic receptors and via the modulation of KV7 channels located on interstitial cells within the renal pelvis wall. PMID- 26278378 TI - Two new species of Euryhaliotrema Kritsky et Boeger, 2002 (Monogenea: Dactylogyridae) from Lutjanus russellii (Bleeker) and L. argentimaculatus (Forsskal) (Teleostei: Lutjanidae) in the South China Sea. AB - Euryhaliotrema russellum sp. n. and Euryhaliotrema tenuiaccessorium sp. n. are described from the gills of Lutjanus russellii (Bleeker) and L. argentimaculatus (Forsskal), respectively, in the South China Sea. Euryhaliotrema russellum sp. n. differs from all other members of Euryhaliotrema Kritsky et Boeger, 2002 by its unique male copulatory organ, a straight tube with a bulbous base and without an accessory piece. Euryhaliotrema tenuiaccessorium sp. n. differs from its congeners by having a copulatory organ with a bulbous base, a meandering copulatory tube with clockwise coil having less than one complete ring, and a slender accessory piece along the middle length of the copulatory tube. All species of Euryhaliotrema are listed and divided to three groups based on morpholgy of the male copulatory organ. PMID- 26278379 TI - The evolution of emaraviruses is becoming more complex: seven segments identified in the causal agent of Rose rosette disease. AB - There are few examples of a plant disease as devastating as rose rosette, a disorder that could lead to total loss for the nursery industry and rosarians alike. Although described over 75 years ago, the causal agent of rose rosette remains elusive. Utilizing the bottleneck created during vector transmission and large scale sequencing it was determined that the causal agent of the disease is rose rosette virus (RRV), a member of the genus Emaravirus. The genome structure of emaraviruses displays significant fluidity and for this reason the genome composition of RRV was revisited, leading to the discovery of three additional segments, one of which is predicted to be bicistronic. PMID- 26278380 TI - Foreword. PMID- 26278381 TI - Origin of colossal permittivity in (In1/2Nb1/2)TiO2via broadband dielectric spectroscopy. AB - (In1/2Nb1/2)TiO2 (IN-T) ceramics were prepared via a solid-state reaction route. X-ray diffraction (XRD) and Raman spectroscopy were used for the structural and compositional characterization of the synthesized compounds. The results indicated that the sintered ceramics have a single phase of rutile TiO2. Dielectric spectroscopy (frequency range from 20 Hz to 1 MHz and temperature range from 10 K to 270 K) was performed on these ceramics. The IN-T ceramics showed extremely high permittivities of up to ~10(3), which can be referred to as colossal permittivity, with relatively low dielectric losses of ~0.05. Most importantly, detailed impedance data analyses of IN-T demonstrated that electron pinned defect-dipoles, interfacial polarization and polaron hopping polarization contribute to the colossal permittivity at high temperatures (270 K); however, only the complexes (pinned electron) and polaron hopping polarization are active at low temperatures (below 180 K), which is consistent with UDR analysis. PMID- 26278382 TI - Regeneration mechanisms of high-lithium content zirconates as CO2 capture sorbents: experimental measurements and theoretical investigations. AB - By combining TGA and XRD measurements with theoretical calculations of the capture of CO2 by lithium-rich zirconates (Li8ZrO6 and Li6Zr2O7), it has been demonstrated that the primary regeneration product during absorption/desorption cycling is in the form of Li2ZrO3. During absorption/desorption cycles, lithium rich zirconates will be consumed and will not be regenerated. This result indicates that among known lithium zirconates, Li2ZrO3 is the best sorbent for CO2 capture. PMID- 26278384 TI - Emissive Ir(III) complexes bearing thienylamido groups on a 1,10-phenanthroline scaffold. AB - The synthesis, structures and photophysical properties of a series of bis cyclometallated Ir(iii) complexes bearing phenylpyrazole (ppz) cyclometallating ligands and phenanthroline-based ancillary ligands containing thienyl- and bithienylamido groups are reported. All complexes are emissive in solution, while in PMMA films strong emission is observed from the thienylamido substituted complex with no emission from the bithienylamido complex. The bithienylamido substituted complex has an excited state lifetime which is significantly longer than the emission lifetime, attributed to the population of non-equilibrated (3)MLCT and (3)LC states in this complex. This represents a rare example of this unusual excited state behaviour. DFT calculations show that the emitting (3)MLCT state and the dark (3)LC state on bithiophene are close in energy and that a large change in the triplet state geometry occurs upon excitation that effectively lowers the energy of the (3)MLCT state below that of the dark (3)LC state. The low quantum yield of the bithienylamido complex is attributed to a structural rearrangement upon relaxation back to the ground state, opening a non radiative decay pathway. PMID- 26278383 TI - Bench-to-bedside review: the effects of hyperoxia during critical illness. AB - Oxygen administration is uniformly used in emergency and intensive care medicine and has life-saving potential in critical conditions. However, excessive oxygenation also has deleterious properties in various pathophysiological processes and consequently both clinical and translational studies investigating hyperoxia during critical illness have gained increasing interest. Reactive oxygen species are notorious by-products of hyperoxia and play a pivotal role in cell signaling pathways. The effects are diverse, but when the homeostatic balance is disturbed, reactive oxygen species typically conserve a vicious cycle of tissue injury, characterized by cell damage, cell death, and inflammation. The most prominent symptoms in the abundantly exposed lungs include tracheobronchitis, pulmonary edema, and respiratory failure. In addition, absorptive atelectasis results as a physiological phenomenon with increasing levels of inspiratory oxygen. Hyperoxia-induced vasoconstriction can be beneficial during vasodilatory shock, but hemodynamic changes may also impose risk when organ perfusion is impaired. In this context, oxygen may be recognized as a multifaceted agent, a modifiable risk factor, and a feasible target for intervention. Although most clinical outcomes are still under extensive investigation, careful titration of oxygen supply is warranted in order to secure adequate tissue oxygenation while preventing hyperoxic harm. PMID- 26278386 TI - Role of Early Growth Response-1 in the Development of Alcohol-Induced Steatosis. AB - Here, we describe research on the involvement of the transcription factor, Early Growth Response- 1 (Egr-1) in alcohol-induced liver injury, specifically, fatty liver (steatosis), one of the earliest and most frequent signs of liver injury that occurs after heavy drinking. Egr-1 is a ubiquitous transcription factor found in nearly all cell types. However, because the liver is the principal site of ethanol oxidation, it sustains the greatest damage from alcohol abuse. Thus, this review focuses on how alcohol consumption causes changes in the hepatic expression of Egr-1, which, in turn causes downstream alterations in the expression of other genes to cause liver pathology. Ironically, while such changes in Egr-1 expression clearly favor steatosis and even fibrosis development, the absence of Egr-1 expression can actually exacerbate liver injury after excessive alcohol consumption or after exposure to other hepatotoxins. The existing literature on Egr-1 is extensive. Here, we confine our initial description of Egr-1 to its principal molecular characteristics, its biological functions, and its involvement in certain pathologies that are either directly or obliquely related to alcoholic liver disease. We describe experimental data that clearly implicate Egr-1 function in alcohol-induced steatosis and fibrosis, showing that ethanol-elicited regulation of Egr-1 expression depends on the generation of acetaldehyde and that the absence of Egr-1 diminishes alcohol induced triglyceride accumulation. Overall, the existing evidence for the involvement of Egr-1 as a key link in alcohol-induced liver disease is strong. The evidence underscores the potential role of Egr-1 and several other transcription factors as therapeutic targets in the alleviation of alcoholic liver disease, which, even after decades of treatment options, still remains difficult to manage in the clinic. PMID- 26278385 TI - The Activation and Function of Autophagy in Alcoholic Liver Disease. AB - Autophagy is an important lysosome-mediated intracellular degradation pathway required for tissue homeostasis. Dysregulation of liver autophagy is closely associated with different liver diseases including alcoholic liver disease. Studies now indicate that autophagy may be induced or suppressed depending on the amount and the duration of ethanol treatment. Autophagy induced by ethanol serves as a protective mechanism, probably by selective degradation of the damaged mitochondria (mitophagy) and excess lipid droplets (lipophagy) and in turn attenuates alcohol-induced steatosis and liver injury. However, the detailed molecular mechanism of selective targeting of mitochondria and lipid is still unclear. Autophagy may possess other functions that protect hepatocytes from ethanol. Understanding these molecular entities would be essential in order to therapeutically module autophagy for treatment of alcoholic liver disease. PMID- 26278387 TI - Review: Precision Cut Liver Slices for the Evaluation of Fatty Liver and Fibrosis. AB - INTRODUCTION: Ethanol metabolism in the liver results in oxidative stress, altered cytokine production and fat accumulation in the liver. Thus, it is thought that the accumulation of benign fat into the liver in conjunction with a second hit leads to liver failure. However, we have recently developed the use of precision-cut liver slices (PCLSs) as an in vitro culture model in which to investigate the pathophysiology of alcohol-induced liver injury. In this review, these studies will be discussed and newer data presented. METHODS: Original investigations into the use of PCLS were obtained from chow fed rats (200-300g). PCLSs were cultured 24-96h in media, 25 mM ethanol, or 25 mM ethanol and 0.5 mM 4 methylpyrazole (4-MP). PCLSs were examined for at different times and evaluated for glutathione (GSH) levels, extent of lipid peroxidation (TBARS assay), cytokine production (ELISA and RT-PCR) and myofibroblast activation. Age-matched rats were fed high fat diets for 13 months, PCLSs were prepared, and evaluated as outlined above. In recently, human and mouse PCLSs were cut, equilibrated, and evaluated using the methods outlined as above. RESULTS: In these studies, it was shown that the PCLSs from rats, mice and human livers retained excellent viability over a 96 hour period of incubation. During this time period, alcohol dehydrogenase, aldehyde dehydrogenase, and cytochrome P4502E1 levels were viable. After 24 hours of ethanol exposure, fatty livers and fibrogenic responses developed and could be prevented/reversed with the 4-MP. In a separate study using overly obese rats, ethanol metabolism was decreased in PCLSs as compared to age-matched controls (AMC). However, higher levels of triglycerides and lipid peroxidation were found in PCLSs from obese rats compared to AMC. Also, increased concentrations of the proinflammatory cytokines (TNF-alpha and IL-6) were found in the culture supernatants. In contrast, decreased levels of reduced glutathione (GSH) and heme oxygenase I (HO-1) levels were detected. CONCLUSION: Within 24h of incubation, ethanol metabolism by PCLSs initiates fat accumulation in the liver at which point there is an activation of myofibroblasts. Thus, fatty liver is the first response to ethanol and sensitizes the liver to other products of oxidative stress that result in inflammation and the start of liver failure ending in cirrhosis. Thus, from these studies it appears that PCLSs can be utilized to determine the mechanisms(s) by which ethanol exposure leads to the development and/or progression of alcoholic liver disease (ALD). PMID- 26278388 TI - Signal Transduction Mechanisms of Alcoholic Fatty Liver Disease: Emer ging Role of Lipin-1. AB - Lipin-1, a mammalian phosphatidic acid phosphatase (PAP), is a bi-functional molecule involved in various signaling pathways via its function as a PAP enzyme in the triglyceride synthesis pathway and in the nucleus as a transcriptional co regulator. In the liver, lipin-1 is known to play a vital role in controlling the lipid metabolism and inflammation process at multiple regulatory levels. Alcoholic fatty liver disease (AFLD) is one of the earliest forms of liver injury and approximately 8-20% of patients with simple steatosis can develop into more severe forms of liver injury, including steatohepatitis, fibrosis/ cirrhosis, and eventually hepatocellular carcinoma (HCC). The signal transduction mechanisms for alcohol-induced detrimental effects in liver involves alteration of complex and multiple signaling pathways largely governed by a central and upstream signaling system, namely, sirtuin 1 (SIRT1)-AMP activated kinase (AMPK) axis. Emerging evidence suggests a pivotal role of lipin-1 as a crucial downstream regulator of SIRT1-AMPK signaling system that is likely to be ultimately responsible for development and progression of AFLD. Several lines of evidence demonstrate that ethanol exposure significantly induces lipin-1 gene and protein expression levels in cultured hepatocytes and in the livers of rodents, induces lipin-1-PAP activity, impairs the functional activity of nuclear lipin-1, disrupts lipin-1 mRNA alternative splicing and induces lipin-1 nucleocytoplasmic shuttling. Such impairment in response to ethanol leads to derangement of hepatic lipid metabolism, and excessive production of inflammatory cytokines in the livers of the rodents and human alcoholics. This review summarizes current knowledge about the role of lipin-1 in the pathogenesis of AFLD and its potential signal transduction mechanisms. PMID- 26278389 TI - Alcoholic Liver Disease: from CYP2E1 to CYP2A5. AB - This article reviews recent studies on CYP2E1-mediated alcoholic liver injury, the induction of CYP2A5 by alcohol and the mechanism for this upregulation, especially the permissive role of CYP2E1 in the induction of CYP2A5 by alcohol and the CYP2E1-ROS-Nrf2 pathway, and protective effects of CYP2A5 against ethanol induced oxidative liver injury. Ethanol can induce CYP2E1, an active generator of reactive oxygen species (ROS), and CYP2E1 is a contributing factor for alcoholinduced oxidative liver injury. CYP2A5, another isoform of cytochrome P450, can also be induced by ethanol. Chronic feeding of ethanol to wild type mice increased CYP2A5 catalytic activity, protein and mRNA levels as compared to pair-fed controls. This induction was blunted in CYP2E1 knockout (cyp2e1-/-) mice but was restored when human CYP2E1 was reintroduced and expressed in cyp2e1-/- mice. Ethanol-induced CYP2E1 co-localized with CYP2A5 and preceded the elevation of CYP2A5. The antioxidants N-acetyl cysteine and vitamin C lowered the alcohol elevation of ROS and blunted the alcohol induction of CYP2A5, but not CYP2E1, suggesting ROS play a novel role in the crosstalk between CYP2E1 and CYP2A5. The antioxidants blocked the activation of Nrf2, a transcription factor known to upregulate expression of CYP2A5. When alcohol-induced liver injury was enhanced in Nrf2 knockout (Nrf2-/-) mice, alcohol elevation of CYP2A5 but not CYP2E1 was also lower in Nrf2-/- mice. CYP2A5 knockout (cyp2a5-/-) mice exhibited an enhanced alcoholic liver injury compared with WT mice as indicated by serum ALT, steatosis and necroinflammation. Alcohol-induced hyperglycemia were observed in cyp2a5-/- mice but not in WT mice. PMID- 26278391 TI - The Hepatic Lipidome: A Gateway to Understanding the Pathogenes is of Alcohol Induced Fatty Liver. AB - Chronic alcohol consumption can lead to the development of alcoholic fatty liver disease. The underlying pathogenic mechanisms however, have not been fully elucidated. Here, we review the current state of the art regarding the application of lipidomics to study alcohol's effect on hepatic lipids. It is clear that alcohol has a profound effect on the hepatic lipidome, with documented changes in the major lipid categories (i.e. fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterol lipids and prenol lipids). Alcohol's most striking effect is the marked change in the hepatic fatty acyl pool. This effect includes increased levels of 18-carbon fatty acyl chains incorporated into multiple lipid species, as well as a general shift toward increased unsaturation of fatty acyl moieties. In addition to our literature review, we also make several recommendations to consider when designing lipidomic studies into alcohol's effects. These recommendations include integration of lipidomic data with other measures of lipid metabolism, inclusion of multiple experimental time points, and presentation of quantitative data. We believe rigorous analysis of the hepatic lipidome can yield new insight into the pathogenesis of alcohol induced fatty liver. While the existing literature has been largely descriptive, the field is poised to apply lipidomics to yield a new level of understanding on alcohol's effects on hepatic lipid metabolism. PMID- 26278392 TI - Role of the Wnt/beta-Catenin Pathway in the Pathogenesis of Alcoholic Liver Disease. AB - The Wnt pathway is a highly conserved signal transduction pathway that plays an important role in diverse aspects of hepatic physiology. The Wnt pathway, consisting of canonical and noncanonical arms, is composed of secreted glycoproteins, cell surface receptors and co-receptors, and complex intracellular regulatory machinery that regulate a large number of cellular functions. beta Catenin is the main effector of the canonical Wnt pathway and hepatocyte-specific loss of the protein leads to increased susceptibility to alcoholic steatohepatitis. Hepatocytes with disrupted beta-catenin demonstrate mitochondrial dysfunction, defective oxidative phosphorylation, and increased oxidative stress. beta- Catenin knockout mice have decreased expression of alcohol metabolizing enzymes and increased blood alcohol levels that along with hypoglycemia and hyperammonemia, lead to increased mortality upon alcohol exposure. Disruption of hepatic beta-catenin affects fatty acid oxidation and fasting ketogenesis and thereby profoundly affects systemic energy homeostasis. Given the combined roles of Wnt/beta-catenin signaling in hepatocellular bioenergetics and regeneration, the Wnt pathway also contributes to alcohol induced hepatic fibrogenesis and hepatocarcinogenesis. Targeting the Wnt/beta catenin pathway represents an attractive strategy for the treatment of alcohol induced liver disease. PMID- 26278390 TI - Structure, Function and Metabolism of Hepatic and Adipose Tissue Lipid Droplets: Implications in Alcoholic Liver Disease. AB - For more than 30 years, lipid droplets (LDs) were considered as an inert bag of lipid for storage of energy-rich fat molecules. Following a paradigm shift almost a decade ago, LDs are presently considered an active subcellular organelle especially designed for assembling, storing and subsequently supplying lipids for generating energy and membrane synthesis (and in the case of hepatocytes for VLDL secretion). LDs also play a central role in many other cellular functions such as viral assembly and protein degradation. Here, we have explored the structural and functional changes that occur in hepatic and adipose tissue LDs following chronic ethanol consumption in relation to their role in the pathogenesis of alcoholic liver injury. PMID- 26278394 TI - Editorial: New Insights into Mechanisms of Alcohol-Induced Fatty Liver. PMID- 26278395 TI - Recent developments in the chemistry of quinazolinone alkaloids. AB - Quinazolinones, an important class of fused heterocyclic alkaloids has attracted high attention in organic and medicinal chemistry due to their significant and wide range of biological activities. There are approximately 150 naturally occurring quinazolinone alkaloids known till 2005. Several new quinazolinone alkaloids (~55) have been isolated in the last decade. Natural quinazolinones with exotic structural features and remarkable biological activities have incited a lot of activities in the synthetic community towards the development of new synthetic strategies and approaches for the total synthesis of quinazolinone alkaloids. This review is focused on these advances in the chemistry of quinazolinone alkaloids in the last decade. This article covers the newly isolated quinazolinone natural products with their biological activities and the recently reported total syntheses of quinazolinone alkaloids from 2006 to 2015. PMID- 26278396 TI - Role of a functional polymorphism in the F2R gene promoter in sarcoidosis. AB - Sarcoidosis is a multisystem granulomatous disease of unknown aetiology characterized by increased inflammation, and results from gene-environment interactions. Proteinase-activated receptor-1 mediates the interplay between coagulation and inflammation. The rs2227744G > A promoter single nucleotide polymorphism has been linked to inflammation, cardiovascular disease and chronic obstructive pulmonary disease exacerbations. Using a case-control study (184 cases with sarcoidosis and 368 controls), we show that the rs2227744A allele significantly associates with protection from sarcoidosis (P = 0.003, OR = 0.68 (0.52-0.88)). PMID- 26278397 TI - Use of UHPLC high-resolution Orbitrap mass spectrometry to investigate the genes involved in the production of secondary metabolites in Aspergillus flavus. AB - The fungus Aspergillus flavus is known for its ability to produce the toxic and carcinogenic aflatoxins in food and feed. While aflatoxins are of most concern, A. flavus is predicted to be capable of producing many more metabolites based on a study of its complete genome sequence. Some of these metabolites could be of great importance in food and feed safety. Here we describe an analytical methodology based on Orbitrap HRMS technology that allows the untargeted determination of fungal metabolites, in support of the study of the function of genes involved in secondary metabolism in fungi. The applied strategy implies the detection and identification of differentially expressed metabolites in extracts of wild-type and mutant fungal strains, using Orbitrap high-resolution mass spectrometry (HRMS) accurate mass data. The suitability of this approach was demonstrated by the confirmation of previously characterised genes involved in the aflatoxin biosynthetic pathway, namely a polyketide synthase (pksA), an oxidoreductase (ordA) and a methyltransferase (omtA) gene. Subsequently, the proposed methodology was applied for the detection and identification of metabolites produced by a yet uncharacterised gene cluster in A. favus, cluster 23. Comparative Orbitrap HRMS analysis of extracts of A. flavus wild-type strain and an over-expression mutant for the transcription factor of gene cluster 23 (lepE) demonstrated that this gene cluster is responsible for the production a set of 2-pyridone derivatives, the leporins. Besides the known derivatives leporin B and leporin B precursor that could be identified by automatic de replication of the accurate mass data, five other compounds belonging to this class of fungal secondary metabolites were detected and identified for the first time, combining MS and multiple-stage MS data. PMID- 26278398 TI - Exploring women's responses to online media coverage of weight loss surgery. AB - The purpose of this study was to understand the reactions of women to online news articles about weight loss surgery and related reader comments. Focus groups were conducted; open-ended questions were asked to elicit responses to existing online news media content related to weight loss surgery. The participants described the online articles as predominantly supportive of weight loss surgery and in response they expressed a desire to see more critical content, including different and competing perspectives. Participants felt the online comments represented extreme perspectives and were predominately negative. These were therefore not viewed as helpful or informative. Nevertheless, readers viewed comments as a form of entertainment. Because of the aggressive and anonymous nature of reader comments in response to online news stories, the participants did not feel comfortable leaving comments themselves on the news sites. Findings highlight the importance of gathering readers' perspectives in response to interactive media content and, in particular, health information. PMID- 26278393 TI - Role of CYP2E1 in Mitochondrial Dysfunction and Hepatic Injury by Alcohol and Non Alcoholic Substances. AB - Alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD) are two pathological conditions that are spreading worldwide. Both conditions are remarkably similar with regard to the pathophysiological mechanism and progression despite different causes. Oxidative stressinduced mitochondrial dysfunction through post-translational protein modifications and/or mitochondrial DNA damage has been a major risk factor in both AFLD and NAFLD development and progression. Cytochrome P450-2E1 (CYP2E1), a known important inducer of oxidative radicals in the cells, has been reported to remarkably increase in both AFLD and NAFLD. Interestingly, CYP2E1 isoforms expressed in both endoplasmic reticulum (ER) and mitochondria, likely lead to the deleterious consequences in response to alcohol or in conditions of NAFLD after exposure to high fat diet (HFD) and in obesity and diabetes. Whether CYP2E1 in both ER and mitochondria work simultaneously or sequentially in various conditions and whether mitochondrial CYP2E1 may exert more pronounced effects on mitochondrial dysfunction in AFLD and NAFLD are unclear. The aims of this review are to briefly describe the role of CYP2E1 and resultant oxidative stress in promoting mitochondrial dysfunction and the development or progression of AFLD and NAFLD, to shed a light on the function of the mitochondrial CYP2E1 as compared with the ER-associated CYP2E1. We finally discuss translational research opportunities related to this field. PMID- 26278399 TI - Comment on the Paper Entitled 'Effect of Erythritol and Xylitol on Dental Caries Prevention in Children'. PMID- 26278400 TI - Catecholaminergic Ventricular Tachycardia, Pregnancy and Teenager: Are They Compatible? AB - Arrhythmias in pregnancy are becoming more common given more available and effective medical, ablation and device treatment options. Several changes associated with pregnancy, increased blood volume, cardiac output, and heart rate secondary to an increased sympathetic state, facilitate more frequent occurrences of arrhythmias throughout the pregnancy and during labor and delivery. We present a case of successful pregnancy in a teenage female with a previous diagnosis of CPVT, followed by a review of the literature. PMID- 26278401 TI - Relaxin-3 receptor (Rxfp3) gene deletion reduces operant sucrose- but not alcohol responding in mice. AB - The pervasive use of refined sugars in highly accessible, palatable foods and persistent exposure to reinforcing food-associated cues has contributed to overconsumption of sugar-rich diets and the current obesity epidemic in Western society. We have shown previously that brain relaxin-3 mRNA levels positively correlate with sucrose and alcohol intake, and that central antagonism of relaxin 3 receptors (RXFP3) attenuates alcohol self-administration and alcohol-seeking in rats, but food-seeking behaviour and palatable food consumption in mice. To further examine the relationship between motivated appetitive behaviours and relaxin-3/RXFP3 signalling, we investigated the effect of Rxfp3 gene deletion in C57BL/6J mice on sucrose and alcohol self-administration and cue-induced reinstatement (RNST) of sucrose- and alcohol-seeking. Acquisition and maintenance of sucrose and alcohol self-administration was assessed in male wild-type (WT) and Rxfp3 knockout (KO) (C57BL/6J(RXFP3TM1) (/) (DGen) ) littermate mice using fixed ratio (FR) schedules of reinforcement. Mice were subsequently challenged with a progressive ratio (PR) test to measure motivation and, following extinction training, re-exposed to reward-associated cues to evaluate RNST of active lever-responding. Wild-type and Rxfp3 KO mice displayed similar acquisition of FR1 sucrose self-administration, but Rxfp3 KO mice responded less when the instrumental requirement was increased to FR3. These mice also showed a lower breakpoint for sucrose and attenuated cue-induced RNST of sucrose-seeking. Notably, no marked genotype differences in alcohol-responding were observed. In mice, endogenous relaxin-3/RXFP3 signalling promotes self-administration of sucrose under high response requirements and cue-induced RNST of sucrose-seeking, but does not apparently regulate motivation to consume alcohol or alcohol-seeking behaviour. PMID- 26278403 TI - Predictive models of lameness in dairy cows achieve high sensitivity and specificity with force measurements in three dimensions. AB - Lameness remains a significant cause of production losses, a growing welfare concern and may be a greater economic burden than clinical mastitis . A growing need for accurate, continuous automated detection systems continues because US prevalence of lameness is 12.5% while individual herds may experience prevalence's of 27.8-50.8%. To that end the first force-plate system restricted to the vertical dimension identified lame cows with 85% specificity and 52% sensitivity. These results lead to the hypothesis that addition of transverse and longitudinal dimensions could improve sensitivity of lameness detection. To address the hypothesis we upgraded the original force plate system to measure ground reaction forces (GRFs) across three directions. GRFs and locomotion scores were generated from randomly selected cows and logistic regression was used to develop a model that characterised relationships of locomotion scores to the GRFs. This preliminary study showed 76 variables across 3 dimensions produced a model with greater than 90% sensitivity, specificity, and area under the receiver operating curve (AUC). The result was a marked improvement on the 52% sensitivity, and 85% specificity previously observed with the 1 dimensional model or the 45% sensitivities reported with visual observations. Validation of model accuracy continues with the goal to finalise accurate automated methods of lameness detection. PMID- 26278405 TI - Central tarsal bone fractures in horses not used for racing: Computed tomographic configuration and long-term outcome of lag screw fixation. AB - REASONS FOR PERFORMING STUDY: There are no reports on the configuration of equine central tarsal bone fractures based on cross-sectional imaging and clinical and radiographic long-term outcome after internal fixation. OBJECTIVES: To report clinical, radiographic and computed tomographic findings of equine central tarsal bone fractures and to evaluate the long-term outcome of internal fixation. STUDY DESIGN: Retrospective case series. METHODS: All horses diagnosed with a central tarsal bone fracture at our institution in 2009-2013 were included. Computed tomography and internal fixation using lag screw technique was performed in all patients. Medical records and diagnostic images were reviewed retrospectively. A clinical and radiographic follow-up examination was performed at least 1 year post operatively. RESULTS: A central tarsal bone fracture was diagnosed in 6 horses. Five were Warmbloods used for showjumping and one was a Quarter Horse used for reining. All horses had sagittal slab fractures that began dorsally, ran in a plantar or plantaromedial direction and exited the plantar cortex at the plantar or plantaromedial indentation of the central tarsal bone. Marked sclerosis of the central tarsal bone was diagnosed in all patients. At long-term follow-up, 5/6 horses were sound and used as intended although mild osteophyte formation at the distal intertarsal joint was commonly observed. CONCLUSIONS: Central tarsal bone fractures in nonracehorses had a distinct configuration but radiographically subtle additional fracture lines can occur. A chronic stress related aetiology seems likely. Internal fixation of these fractures based on an accurate diagnosis of the individual fracture configuration resulted in a very good prognosis. PMID- 26278404 TI - GacA is essential for Group A Streptococcus and defines a new class of monomeric dTDP-4-dehydrorhamnose reductases (RmlD). AB - The sugar nucleotide dTDP-L-rhamnose is critical for the biosynthesis of the Group A Carbohydrate, the molecular signature and virulence determinant of the human pathogen Group A Streptococcus (GAS). The final step of the four-step dTDP L-rhamnose biosynthesis pathway is catalyzed by dTDP-4-dehydrorhamnose reductases (RmlD). RmlD from the Gram-negative bacterium Salmonella is the only structurally characterized family member and requires metal-dependent homo-dimerization for enzymatic activity. Using a biochemical and structural biology approach, we demonstrate that the only RmlD homologue from GAS, previously renamed GacA, functions in a novel monomeric manner. Sequence analysis of 213 Gram-negative and Gram-positive RmlD homologues predicts that enzymes from all Gram-positive species lack a dimerization motif and function as monomers. The enzymatic function of GacA was confirmed through heterologous expression of gacA in a S. mutans rmlD knockout, which restored attenuated growth and aberrant cell division. Finally, analysis of a saturated mutant GAS library using Tn-sequencing and generation of a conditional-expression mutant identified gacA as an essential gene for GAS. In conclusion, GacA is an essential monomeric enzyme in GAS and representative of monomeric RmlD enzymes in Gram-positive bacteria and a subset of Gram-negative bacteria. These results will help future screens for novel inhibitors of dTDP-L-rhamnose biosynthesis. PMID- 26278406 TI - A novel detection technique of polyamide binding sites by photo-induced electron transfer in (Br)U substituted DNA. AB - We report the photochemistry of (Br)U substituted DNA as a versatile platform to investigate the binding sites of pyrene conjugated pyrrole imidazole polyamides (PIPs). The results suggest that the approach can be used on a routine basis for the screening of polyamide binding sites. PMID- 26278408 TI - Use of Plastic Needles for Early Arteriovenous Fistula Cannulation. AB - BACKGROUND: The native arteriovenous fistula (AVF) needs maturation before it can be used. Needling done before time may result in haematoma formation, miscannulation or even access loss. METHODS: This retrospective study included 20 patients with AVFs punctured with fluoroplastic dialysis catheters within 30 days after access creation and 19 historical controls. RESULTS: The time to first puncture was 2-29 days for the study group and 1-26 days for the control group. The incidences of haematoma were 16.7 and 48 per 1,000 dialysis sessions for plastic and metal needles, respectively. Estimated primary functional fistula survival at 3, 6 and 12 months were 95, 90 and 74% for the study group and 79, 67 and 60% for the control group (p = 0.106), respectively. CONCLUSIONS: Use of plastic needles enables safe AVF cannulation. If applied judiciously, it can minimize or even avoid catheter use. PMID- 26278407 TI - The domain of neuronal firing on a plane of input current and conductance. AB - The activation of neurotransmitter receptors increases the current flow and membrane conductance and thus controls the firing rate of a neuron. In the present work, we justified the two-dimensional representation of a neuronal input by voltage-independent current and conductance and obtained experimentally and numerically a complete input-output (I/O) function. The dependence of the steady state firing rate on the input current and conductance was studied as a two parameter I/O function. We employed the dynamic patch clamp technique in slices to get this dependence for the whole domain of two input signals that evoke stationary spike trains in a single neuron (Omega-domain). As found, the Omega domain is finite and an additional conductance decreases the range of spike evoking currents. The I/O function has been reproduced in a Hodgkin-Huxley-like model. Among the simulated effects of different factors on the I/O function, including passive and active membrane properties, external conditions and input signal properties, the most interesting were: the shift of the right boundary of the Omega-domain (corresponding to the exCitation block) leftwards due to the decrease of the maximal potassium conductance; and the reduction of the Omega domain by the decrease of the maximal sodium concentration. As found in experiments and simulations, the Omega-domain is reduced by the decrease of extracellular sodium concentration, by cooling, and by adding slow potassium currents providing interspike interval adaptation; the Omega-domain height is increased by adding color noise. Our modeling data provided a generalization of I/O dependencies that is consistent with previous studies and our experiments. Our results suggest that both current flow and membrane conductance should be taken into account when determining neuronal firing activity. PMID- 26278409 TI - Risk factors for tuberculosis in patients receiving tumour necrosis factor-alpha blockers: what do we really know? PMID- 26278410 TI - Solvent-Free Click-Mechanochemistry for the Preparation of Cancer Cell Targeting Graphene Oxide. AB - Polyethylene glycol-functionalized nanographene oxide (PEGylated n-GO) was synthesized from alkyne-modified n-GO, using solvent-free click-mechanochemistry, i.e., copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The modified n-GO was subsequently conjugated to a mucin 1 receptor immunoglobulin G antibody (anti MUC1 IgG) via thiol-ene coupling reaction. n-GO derivatives were characterized with Fourier-transformed infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA), Bradford assay, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and atomic force microscopy (AFM). Cell targeting was confirmed in vitro in MDA-MB-231 cells, either expressing or lacking MUC1 receptors, using flow cytometry, confocal laser scanning microscopy (CLSM) and multiphoton (MP) fluorescence microscopy. Biocompatibility was assessed using the modified lactate dehydrongenase (mLDH) assay. PMID- 26278411 TI - Predicting Suitable Habitats for the Vulnerable Eastern Hoolock Gibbon, Hoolock leuconedys, in India Using the MaxEnt Model. AB - The eastern hoolock gibbon, Hoolock leuconedys, is categorized as Vulnerable on the IUCN Red List and assessed as a Schedule I species of the Wildlife (Protection) Act of 1972 in India. We predict the potential habitat of H. leuconedys in the state of Arunachal Pradesh, India, using the Maximum Entropy (MaxEnt) distribution modelling algorithm. The model was developed using 90 known localities of H. leuconedys in the state. Nineteen environmental parameters along with 12 normalized difference vegetation index (NDVI) layers, elevation and land use and land cover (LULC) were used in the modelling. Amongst the environmental input variables, the precipitation of the coldest quarter (BIO 19) had the highest contribution to the model (26.03%) and the twelve NDVI layers collectively contributed 60.91%. Two districts, Lower Dibang Valley and Lohit, which are known to contain H. leuconedys, occupied 64.75% of the predicted distribution area of the species. Thus, we aid in the identification of suitable areas for the reintroduction program of H. leuconedys that is planned by the Gibbon Conservation Breeding Centre, Biological Park, Itanagar, Arunachal Pradesh, India. PMID- 26278412 TI - Maternal Nicotine Exposure Induces Epithelial-Mesenchymal Transition in Rat Offspring Lungs. AB - BACKGROUND: Maternal nicotine exposure induces lung injuries and fibrosis in rat offspring. Epithelial-mesenchymal transition (EMT) following lung injury is a process in which epithelial cells mediate tissue repair. OBJECTIVE: To determine the effects of maternal nicotine exposure on EMT in neonatal rat lungs. METHODS: Nicotine was administered to pregnant Sprague-Dawley rats using a subcutaneous osmotic minipump that delivered a dose of 6 mg/kg/day on gestational days 7-21 or from gestational day 7 to postnatal day 14. A control group received an equal volume of saline. RESULTS: The percentage of 8-hydroxy-2'-deoxyguanosine-positive cells in nuclear staining was significantly higher, the E-cadherin protein expression was significantly lower, and the N-cadherin protein expression was significantly higher in rats born to prenatal and postnatal nicotine-treated dams than in those born to prenatal saline- and nicotine-treated dams on postnatal day 7. These characteristics of EMT were associated with a significant increase in alpha-smooth muscle actin (SMA) expression on postnatal day 21. Rats born to prenatal and postnatal nicotine-treated dams showed significantly higher alpha SMA expression and total collagen than those born to prenatal saline- and nicotine-treated dams on postnatal day 21. The number of cells expressing fibroblast-specific protein 1 and vimentin was higher in rats born to prenatal and postnatal nicotine-treated dams than in those born to prenatal saline- and nicotine-treated dams on postnatal days 7 and 21. CONCLUSIONS: Maternal nicotine exposure during gestation and lactation induces EMT and contributes to lung fibrosis in rat offspring. PMID- 26278413 TI - A 10-Year Follow-Up Study of Subjects Recruited in a Health Campaign for the Early Diagnosis of Cutaneous Melanoma: Suggestions for the Screening Timetable. AB - BACKGROUND: Cutaneous melanoma affects people at a relatively young age. The possibility of making a screening at the population level is strongly limited because of the high costs and the shortage of well-trained operators. OBJECTIVE: To evaluate the possibility of a sustainable timetable of screening examinations for cutaneous melanoma. METHODS: Subjects who contacted the Lega Italiana per la Lotta contro i Tumori (Italian League against Cancer) between January 2001 and December 2004 were followed up to December 2013 through linkage with the Trento Skin Cancer Registry. The cumulative incidence of cutaneous melanoma was calculated and compared with that observed in the general population. RESULTS: Fifteen newly diagnosed cutaneous melanomas were observed in 3,635 subjects during the screening phase, while 14 new cases were diagnosed within December 2013, in the period of follow-up after the screening. The 95% confidence interval for the cumulative incidence of screened subjects included the cumulative incidence of the general population. No new cutaneous melanomas were detected in a 2-year period, after the first examination, 2 cases within 3 years. CONCLUSIONS: Based on our study, we think that in a selected population a screening programme can be performed every 2-3 years. This could help make a screening possible/sustainable for the early diagnosis of cutaneous melanoma in a public health context. PMID- 26278414 TI - Immune tolerance induction in patients with haemophilia a and inhibitors: effectiveness and cost analysis in an European Cohort (The ITER Study). AB - INTRODUCTION: Although immune tolerance induction (ITI) is considered the first choice treatment to eradicate inhibitors in haemophilia A patients, little is known about outcomes determinants and cost magnitude. AIM AND METHODS: A retrospective, multicentre study was conducted to assess the relationship between ITI outcome, clinical and treatment characteristics and cost of ITI treatment in haemophilia A patients. Data from 12 months before inhibitor diagnosis to 12 months after ITI completion were collected. Treatment cost was calculated in the third-party perspective and expressed as mean ? per patient-month. Cox regression models were used to identify predictors of better outcome and the time taken to achieve tolerance. RESULTS: Seventy-one patients, aged 0.4-41 years (median: 3.8 years) at ITI start, were enrolled. Undetectable inhibitor was achieved in 84.5% of patients and inhibitor eradication with normal factor VIII (FVIII) pharmacokinetics in 74.2%. Median time to successful tolerance was 10.7 months (range 2.0-90.0 months). Peak inhibitor level on ITI was a significant predictor of ITI success. Breakthrough bleeding event incidence during ITI was associated with time to success. The mean cost of treatment for the time period between inhibitor diagnosis and ITI start was ?3188 per patient-month (92.1% for bypassing agents), and ?60 078 during ITI (76.8% for FVIII use in ITI). CONCLUSION: Immune tolerance induction in this patient cohort was successful in 84.5% of patients with a mean cost of ?60 000 per patient-month. This high cost is dwarfed by comparison with the prospect of lifelong care of an inhibitor patient, in addition to gains in life expectancy and health-related quality of life. PMID- 26278415 TI - All-trans-retinoic acid modulates nitric oxide and interleukin-17A production by peripheral blood mononuclear cells from patients with Alzheimer's disease. AB - BACKGROUND: Alzheimer's disease (AD), the most common form of dementia in the elderly, is a neurodegenerative disorder associated with a complex pathophysiology. It is accepted that inflammation contributes to the pathogenesis of AD. All-trans-retinoic acid (ATRA) is a bioactive derivative of vitamin A that has shown immunomodulatory effects in many immune disorders. OBJECTIVES: In our study, we aimed to investigate in vitro immunomodulatory effects of ATRA on inducible nitric oxide synthase (iNOS) expression and interleukin-17A production during AD. METHODS: Peripheral blood mononuclear cells (PBMCs) isolated from 30 Algerian AD patients and 14 age-matched nondemented controls were treated (or not) with ATRA. Production of NO and IL-17A in culture media was measured by the modified Griess method and enzyme-linked immunosorbent assay, respectively. Expression of iNOS in PBMCs was examined by fluorescence immunostaining. RESULTS: Our results showed higher spontaneous in vitro production of NO related to overexpression of iNOS in AD patients compared to controls. Remarkably, ATRA treatment showed an important downregulatory effect on NO production and iNOS expression in patients. This effect was associated with a reduction in IL-17A production and increased IL-10 release. CONCLUSIONS: Taken together, our results indicate that ATRA exerts anti-inflammatory effects in AD. Furthermore, ATRA represents a promising tool for monitoring inflammatory responses associated with disease progression. PMID- 26278416 TI - Effects of Astragaloside IV Against the TGF-beta1-Induced Epithelial-to Mesenchymal Transition in Peritoneal Mesothelial Cells by Promoting Smad 7 Expression. AB - BACKGROUND/AIMS: To investigate the effect of Astragaloside IV (AS-IV) on the regulation of the TGF-beta1/Smad signaling pathway in peritoneal mesothelial cells with an epithelial-to-mesenchymal transition (EMT). METHODS: EMT of human peritoneal mesothelial cells (HMrSV5) was induced using 2 ng/ml TGF-beta1. Cells were randomly divided into a vehicle group, a vehicle group with AS-IV, a TGF beta1 treated group, and a TGF-beta1 treated group receiving varied doses of AS IV or NAC. Real-time quantitative PCR and western blot were used to detect the expression of genes and proteins associated with the TGF-beta1/Smad signaling pathway and EMT. DCFH-DA was used to detect the generation of ROS in HMrSV5 cells, and a transwell migration assay was used to verify the capacity of AS-IV to inhibit EMT in HMrSV5 cells. Lentiviruses were used as carriers for the overexpression or knockdown of the Smad7 gene. RESULTS: Expression levels of E cadherin (epithelial marker) was decreased and vimentin, alpha-SMA (EMT markers) and collagen I (extracellular matrix protein) phospho-Smad2/3, Snail1 and Snail2 was increased significantly in the TGF-beta1-treated HMrSV5 cells. AS-IV was associated with downregulated expression of vimentin and phospho-Smad2/3 in a dose-dependent manner, while the expression of Smad7 increased. Silenced or forced expression of Smad7 verified its role in the inhibitory effect of AS-IV on TGF-beta1-induced EMT in HMrSV5 cells. CONCLUSION: AS-IV effectively promotes the upregulation of Smad7 in the TGF-beta1/Smad signaling pathway during the EMT of HMrSV5 cells, indicating its potential therapeutic effect for the control of PF. PMID- 26278417 TI - Does CSE1L Overexpression Affect Distant Metastasis Development in Breast Cancer? AB - BACKGROUND: CSE1L (chromosome segregation 1-like) is the human homologue to the yeast gene CSE1, and is related to invasion and metastasis in cancer progression. The aim of this study was to investigate the potential role of CSE1L expression in distant metastasis of breast cancer. PATIENTS AND METHODS: A total of 71 breast cancer patients were included in this study. Clinical characteristics and CSE1L status were evaluated. Immunohistochemistry was performed on formalin fixed, paraffin-embedded archival breast tumor tissue. The results of CSE1L staining were analyzed according to the percentage of immunoreactive cells. RESULTS: 34 patients had distant metastasis and 37 did not. The mean age of the patients was 50.5 +/- 12.1 years. Age, tumor size, and hormone receptor status were similar in patients with distant metastasis and in those without. A statistically significant relationship was found between nuclear CSE1L expression and distant metastasis of breast cancer. Lymph node metastasis and nuclear grade were other factors affecting distant metastasis. CONCLUSION: There is a relationship between nuclear CSE1L overexpression and distant metastasis in breast cancer. CSE1L status may therefore become a valuable prognostic tool in the future. PMID- 26278418 TI - Why gender matters in the solution towards safe sanitation? Reflections from rural India. AB - While the topic of women and water, sanitation and hygiene is a widely accepted concern among academics and activists, it continues to be an issue in developing countries with serious consequences. Based on a qualitative research conducted in rural Uttar Pradesh, India, the paper affirms that sanitation issues for women and girls are compounded by inequitable gender norms that put them at greater risk of experiencing violence and multiple health vulnerabilities. Women, despite having a high demand for safe toilet facilities, continue to practise unsafe sanitation. The findings highlight the role of three structural constraints as the key factors influencing toilet construction and use: poverty, inadequate sanitation policy and its implementation and gender-based power dynamics at the household level. The paper concludes by emphasising the relevance of engendering sanitation programmes and policies by involving women and girls in the planning process to ensure that dignified and gender-sensitive sanitation solutions are developed. The paper also stresses the need to have measures for strengthening and effectively implementing a sanitation policy for the poor and for programmes to work with both men and women to address gender power relations which influence toilet adoption and use. PMID- 26278420 TI - Shared decision-making, control preferences and psychological well-being in patients with RPE65 deficiency awaiting experimental gene therapy. AB - PURPOSE: Retinal gene therapy trials are currently ongoing in a small number of inherited retinal disorders and this number is expected to rise significantly. The aim of this study was to analyze the psychological aspects of patients with RPE65 deficiency awaiting potential enrollment in gene therapy trials. METHODS: Five patients with genetically proven RPE65 deficiency took part in this study. They were asked to complete the German versions of (i) the Patient Health Questionnaire (PHQ-D), (ii) the National Eye Institute Visual Function Questionnaire (NEI-VFQ), (iii) the Shared Decision Making Questionnaire (PEF-FB 9), and (iv) the Autonomy Preference Index (API-Dm), and in addition they took part in qualitative interviews. RESULTS: The evaluations of the questionnaires and the interviews showed that the patients have quite high information needs and wish to take part in medical decisions. The perspective to participate in gene therapy trials does not seem to cause pronounced worries. Only the insecurity about if and when enrollment in a trial takes place may be burdensome. DISCUSSION: This study generated important data about the psychological situation of patients awaiting potential enrollment in clinical trials, which can be used to improve patient care in the increasing number of future gene therapy trials around the world. PMID- 26278419 TI - The Effect of Contact Precautions on Frequency of Hospital Adverse Events. AB - OBJECTIVE: To determine whether use of contact precautions on hospital ward patients is associated with patient adverse events DESIGN: Individually matched prospective cohort study SETTING: The University of Maryland Medical Center, a tertiary care hospital in Baltimore, Maryland METHODS: A total of 296 medical or surgical inpatients admitted to non-intensive care unit hospital wards were enrolled at admission from January to November 2010. Patients on contact precautions were individually matched by hospital unit after an initial 3-day length of stay to patients not on contact precautions. Adverse events were detected by physician chart review and categorized as noninfectious, preventable and severe noninfectious, and infectious adverse events during the patient's stay using the standardized Institute for Healthcare Improvement's Global Trigger Tool. RESULTS: The cohort of 148 patients on contact precautions at admission was matched with a cohort of 148 patients not on contact precautions. Of the total 296 subjects, 104 (35.1%) experienced at least 1 adverse event during their hospital stay. Contact precautions were associated with fewer noninfectious adverse events (rate ratio [RtR], 0.70; 95% confidence interval [CI], 0.51-0.95; P=.02) and although not statistically significant, with fewer severe adverse events (RtR, 0.69; 95% CI, 0.46-1.03; P=.07). Preventable adverse events did not significantly differ between patients on contact precautions and patients not on contact precautions (RtR, 0.85; 95% CI, 0.59-1.24; P=.41). CONCLUSIONS: Hospital ward patients on contact precautions were less likely to experience noninfectious adverse events during their hospital stay than patients not on contact precautions. PMID- 26278421 TI - Validity of the Hochberg procedure revisited for clinical trial applications. AB - There is much interest in using the Hochberg procedure (HP) for statistical tests on primary endpoints of confirmatory clinical trials. The procedure is simple to use and enjoys more power than the Bonferroni and the Holm procedures. However, the HP is not assumption free like the other two procedures. It controls the familywise type I error rate when test statistics (used for statistical tests) are independent or if dependent satisfy a conditionally independent formulation. Otherwise, its properties for dependent tests at present are not fully understood. Consequently, its use for confirmatory trials, especially for their primary endpoints, remains worrisome. Confirmatory trials are typically designed with 1-2 primary endpoints. Therefore, a question was raised at the Food and Drug Administration as to whether the HP is a valid test for the simple case of performing treatment-to-control comparisons on two primary endpoints when their test statistics are not independent. Confirmatory trials for statistical tests normally use simple test statistics, such as the normal Z, student's t, and chi square. The literature does include some work on the HP for dependent cases covering these test statistics, but concerns remain regarding its use for confirmatory trials for which endpoint tests are mostly of the dependent kind. The purpose of this paper is therefore to revisit this procedure and provide sufficient details for better understanding of its performance for dependent cases related to the aforementioned question. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. PMID- 26278422 TI - Access to Kidney Transplantation: Is There a Potential Conflict of Interest? PMID- 26278424 TI - Scientific overview: CSCI-CITAC Annual General Meeting and Young Investigators' Forum 2014. AB - The Canadian Society of Clinician Investigators (CSCI) and Clinical Investigator Trainee Association of Canada/Association des cliniciens-chercheurs en formation du Canada (CITAC/ACCFC) annual general meeting (AGM) was held in Toronto during November 21-24, 2015 for the first time in conjunction with the University of Toronto Clinician-Investigator Program Research Day. The overall theme for this year's meeting was the role of mentorship in career development, with presentations from Dr. Chaim Bell (University of Toronto), Dr. Shurjeel Choudhri (Bayer Healthcare), Dr. Ken Croitoru (University of Toronto), Dr. Astrid Guttman (University of Toronto), Dr. Prabhat Jha (University of Toronto) and Dr. Sheila Singh (McMaster University). The keynote speakers of the 2014 AGM included Dr. Qutayba Hamid, who was presented with the Distinguished Scientist Award, Dr. Ravi Retnakaran, who was presented with the Joe Doupe Award, and Dr. Lorne Babiuk, who was the CSCI-RCPSC Henry Friesen Award winner. The highlight of the conference was, once again, the outstanding scientific presentations from the numerous clinician investigator (CI) trainees from across the country who presented at the Young Investigators' Forum. Their research topics spanned the diverse fields of science and medicine, ranging from basic science to cutting-edge translational research, and their work has been summarized in this review. Over 120 abstracts were presented at this year's meeting. This work was presented during two poster sessions, with the six most outstanding submitted abstracts presented in the form of oral presentations during the President's Forum. PMID- 26278425 TI - Rosuvastatin Lowers Systemic Inflammatory Response in Coronary Artery Bypass Graft Accompanied by Cardiopulmonary Bypass Surgery: A Randomized Controlled Study. AB - PURPOSE: Cardiopulmonary bypass (CPB) is commonly associated with a systemic inflammatory response that may lead to severe complications. Classic signs of systemic inflammatory response syndrome are complement activation and changes in cytokine and acute phase reactant levels. The effects of rosuvastatin after CPB on interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-18 (IL-18) and High Sensitivity C-Reactive Protein (hs-CRP) levels were investigated. METHODS: Thirty seven male and thirteen female patients (total=50) aged 42 to 78 years, who had coronary bypass surgery due to coronary artery disease were randomly divided into two groups. The 25 patients in the control group were administered placebos. The 25 in the treatment group were administered 20 mg rosuvastatin tablets daily between preoperative day 7 and postoperative day 28. Blood samples were taken at six time points; before induction of anesthesia (T1), during CPB (T2), five minutes after removal of cross clamp (T3), after protamine infusion (T4), postoperative day three (T5) and postoperative day 28 (T6). Data points were expressed as mean +/- standard deviation (SD). RESULTS: Rosuvastatin lowered IL-6 levels at T4, T5 and T6 time points (T4, T5, T6 p < 0.05), and elevated IL-10 levels at T3 and T4 (T3, T4 p < 0.05). IL-18 levels were also elevated at multiple time points. Rosuvastatin also lowered hs-CRP levels and cholesterol levels at T6 (p < 0.05). CONCLUSION: Administering 20 mg/day of rosuvastatin between preoperative day 7 and postoperative day 28 may result in fewer complications in certain (especially intraoperative) cases of systemic inflammatory response caused by the CPB technique used in coronary bypass surgery. PMID- 26278423 TI - Antigen archiving by lymph node stroma: A novel function for the lymphatic endothelium. AB - Secondary lymphoid stroma performs far more functions than simple structural support for lymphoid tissues, providing a host of soluble and membrane-bound cues to trafficking leukocytes during inflammation and homeostasis. More recently it has become clear that stromal cells can manipulate T-cell responses, either through direct antigen-mediated stimulation of T cells or more indirectly through the retention and management of antigen after viral infection or vaccination. In light of recent data, this review provides an overview of stromal cell subsets and functions during the progression of an adaptive immune response with particular emphasis on antigen capture and retention by follicular dendritic cells as well as the recently described "antigen archiving" function of lymphatic endothelial cells (LECs). Given its impact on the maintenance of protective immune memory, we conclude by discussing the most pressing questions pertaining to LEC antigen capture, archiving and exchange with hematopoetically derived antigen-presenting cells. PMID- 26278426 TI - The Effects of the Angiotensin Converting Enzyme Inhibitor Enalapril and the Angiotensin II Type 1 Receptor Blocker Losartan on Fracture Healing in Rats. AB - PURPOSE: Angiotensin converting enzyme inhibitors (ACEI) and type I angiotensin receptor blockers (ARB) have been shown to exert significant effects on bone tissue via a local renin-angiotensin-aldosterone system (RAS). The aim of our study was to delineate their influences on fracture healing process. METHODS: Sixty adult male Wistar Albino rats were divided into three groups. After undergoing surgical femoral fracture and fixation, the ACEI group received 10 mg/kg of Enalapril, the ARB group received 10 mg/kg of Losartan and the Control group did not receive any medication. Fracture healing was evaluated at second and fifth postoperative weeks by the Lane-Sandhu radiological staging system and by histological scoring system of Huoet al. ACE expression in fracture callus was studied by immunohistochemistry. RESULTS: Both ACEI and ARB groups showed less fibrous tissue in the fracture area at the second week, but the histologic score differences were significant only between Control and ARB groups. At the fifth week, however, both radiological and histological scores for the ACEI group were significantly higher than both ARB and Control groups, while the scores for ARB and Control groups were similar. The presence of ACE expression in fracture callus was also observed. CONCLUSION: ACEIs had significant positive effects on fracture repair. Losartan failed to display these stimulatory effects, which suggests that local RAS in bone tissue exerts its actions via alternative receptors or pathways than the AT1 receptor. PMID- 26278427 TI - Sensitivity and Specificity of Diffusion-Weighted Magnetic Resonance Imaging in Diagnosis of Bladder Cancers. AB - PURPOSE: Our study is designed to examine the diagnostic performance of diffusion weighted magnetic resonance imaging (DW-MRI) for bladder cancers (BC), and to determine whether DW-MRI can differentiate muscle invasive bladder cancer (MIBC) from non-MIBC (NMIBC). METHODS: A meta-analysis was performed of published studies that investigated the performance of DW-MRI for BC. These studies were retrieved from scientific literature databases using sensitive electronic search strategies. The STATA 12.0 and Meta-disc software were employed for statistical analyses of data extracted from selected studies. RESULTS: Our search initially returned 230 articles, of which 11 met the inclusion criteria and were enrolled into the final meta-analysis. Five of the included studies reported the diagnostic performance of DW-MRI for BC with a cumulative total of 243 BC patients and 82 healthy subjects. Eight studies investigated the diagnostic performance of DW-MRI for differentiating MIBC from NMIBC, involving 259 MIBC lesions and 515 NMIBC lesions. Meta-analysis results were as follows: the diagnostic performance of DW-MRI for BC (sensitivity: 0.95 [0.75-0.99]; specificity: 0.85 [0.74-0.92]; positive likelihood ratio: 6.45 [3.64-11.42]; negative likelihood ratio: 0.055 [0.009-0.333]; diagnostic odds ratio: 117.11 [19.37-708.05]; area under the curve (AUC): 0.91); the diagnostic performance of DW-MRI to differentiate MIBC from NMIBC (sensitivity: 0.85 [0.76 - 0.91]; specificity: 0.90 [0.87 - 0.93]; positive likelihood ratio:8.81[6.43 - 12.07]; negative likelihood ratio: 0.16 [0.10 - 0.28]; diagnostic odds ratio: 53.95 [25.68 - 113.33]; AUC: 0.92). CONCLUSION: DW-MRI has an outstanding diagnostic performance, with advanced sensitivity and specificity, for imaging of bladder cancers and for differentiating MIBC from NMIBC. PMID- 26278429 TI - Improving medication adherence in African-American women living with HIV/AIDS: Leveraging the provider role and peer involvement. AB - African-American women continue to be disproportionately affected by HIV-related morbidity and mortality. To address the burden of HIV/AIDS among this at-risk population, there is need to gain a better understanding of the factors that influence and affect their care-seeking behavior and specifically adherence to antiretroviral treatment. A preliminary qualitative study was conducted with a sample of the target population (n = 10) using grounded theory as the methodological approach. Similarly, 21 healthcare providers - physicians, pharmacists, nurses, and case managers - were then interviewed. A thematic analysis of the transcripts compared care-provider perceptions and narrated experiences with those from the patient participants. Themes related to patient care perceived to enhance medication adherence included (1) provider-patient relationship; (2) holistic and patient-centered care; (3) adequacy of patient education and counseling; (4) modeling adherence behavior; and (5) motivation. Two intervention strategies are proposed - Peer educators as an integral part of the care team and Patient Advisory Groups as a feedback mechanism to enhance effective delivery of patient care in the target population. This exploratory research lays a foundation for the design of targeted interventions to improve linkage to care and enhance medication adherence in African-American women living with HIV/AIDS. PMID- 26278430 TI - Chemometric analysis of multisensor hyperspectral images of precipitated atmospheric particulate matter. AB - The chemometric analysis of multisensor hyperspectral data allows a comprehensive image-based analysis of precipitated atmospheric particles. Atmospheric particulate matter was precipitated on aluminum foils and analyzed by Raman microspectroscopy and subsequently by electron microscopy and energy dispersive X ray spectroscopy. All obtained images were of the same spot of an area of 100 * 100 MUm(2). The two hyperspectral data sets and the high-resolution scanning electron microscope images were fused into a combined multisensor hyperspectral data set. This multisensor data cube was analyzed using principal component analysis, hierarchical cluster analysis, k-means clustering, and vertex component analysis. The detailed chemometric analysis of the multisensor data allowed an extensive chemical interpretation of the precipitated particles, and their structure and composition led to a comprehensive understanding of atmospheric particulate matter. PMID- 26278431 TI - Mapping the UV Photophysics of Platinum Metal Complexes Bound to Nucleobases: Laser Spectroscopy of Isolated Uracil.Pt(CN)4(2-) and Uracil.Pt(CN)6(2-) Complexes. AB - We report the first UV laser spectroscopic study of isolated gas-phase complexes of platinum metal complex anions bound to a nucleobase as model systems for exploring at the molecular level the key photophysical processes involved in photodynamic therapy. Spectra of the Pt(IV)(CN)6(2-).Ur and Pt(II)(CN)4(2-).Ur complexes were acquired across the 220-320 nm range using mass-selective photodepletion and photofragment action spectroscopy. The spectra of both complexes reveal prominent UV absorption bands (lambdamax = 4.90 and 4.70 eV) that we assign primarily to excitation of the Ur pi-pi* localized chromophore. Distinctive UV photofragmentation products are observed for the complexes, with Pt(IV)(CN)6(2-).Ur photoexcitation resulting in complex fission, while Pt(II)(CN)4(2-).Ur photoexcitation initiates a nucleobase proton-transfer reaction across 4.4-5.2 eV and electron detachment above 5.2 eV. The observed photofragments are consistent with ultrafast decay of a Ur localized excited state back to the electronic ground state followed by intramolecular vibrational relaxation and ergodic complex fragmentation. PMID- 26278432 TI - Superatomic Orbitals under Spin-Orbit Coupling. AB - The Au25(SR)18(-) cluster has been the poster child of success in applying the superatom complex concept and remains the most studied system of all of the monolayer-protected metal clusters. In this Letter, we try to solve a mystery about this cluster: the low-temperature UV-vis absorption spectrum shows double peaks below 2.0 eV while simulation by scalar relativistic time-dependent density functional theory (TDDFT) shows only one peak in this region. Using a recently implemented two-component TDDFT, we show that spin-orbit coupling (SOC) leads to those two peaks by splitting the 1P superatomic HOMO orbitals. This work highlights the importance of SOC in understanding the electronic structure and optical absorption of thiolated gold nanoclusters, which has not been realized previously. PMID- 26278433 TI - Toward Quantitative Measurements of Enzyme Kinetics by Dissolution Dynamic Nuclear Polarization. AB - Dissolution dynamic nuclear polarization (D-DNP) experiments enabled us to study the kinetics of the enzymatic phosphorylation reaction of glucose to form glucose 6-phosphate (G6P) by hexokinase (HK), with or without the presence of an excess of G6P, which is known to be an inhibitor of the enzyme. Against all expectations, our observations demonstrate that the phosphorylation of both alpha and beta glucose anomers occurs with comparable kinetics. The catalytic constant of the reaction was estimated based on a simple kinetic model tailored for hyperpolarized systems. PMID- 26278434 TI - Inelastic Scattering of NO by Kr: Rotational Polarization over a Rainbow. AB - We use molecular beams and ion imaging to determine quantum state resolved angular distributions of NO radicals after inelastic collision with Kr. We also determine both the sense and the plane of rotation (the rotational orientation and alignment, respectively) of the scattered NO. By full selection and then detection of the quantum parity of the NO molecule, our experiment is uniquely sensitive to quantum interference. For forward-scattered NO, we report hitherto unseen changes in the plane and sense of rotation with scattering angle and show, remarkably, that the rotation of the NO molecule after collision can be near maximally oriented for certain transitions and scattering angles. These effects are enhanced by the full parity selection in the experiment and result from the interplay between attractive and repulsive forces. PMID- 26278435 TI - Comparison of Ag and SiO2 Nanoparticles for Light Trapping Applications in Silicon Thin Film Solar Cells. AB - Plasmonic and photonic light trapping structures can significantly improve the efficiency of solar cells. This work presents an experimental and computational comparison of identically shaped metallic (Ag) and nonmetallic (SiO2) nanoparticles integrated to the back contact of amorphous silicon solar cells. Our results show comparable performance for both samples, suggesting that minor influence arises from the nanoparticle material. Particularly, no additional beneficial effect of the plasmonic features due to metallic nanoparticles could be observed. PMID- 26278436 TI - Correction to "Structural Evolution of Supercritical CO2 across the Frenkel Line". PMID- 26278437 TI - Monitoring the Phase Formation of Coevaporated Lead Halide Perovskite Thin Films by in Situ X-ray Diffraction. AB - Perovskite solar cells based on (CH3NH3)Pb(I,Cl)3 have recently demonstrated rapidly increasing cell efficiencies. Here, we show progress identifying phases present during the growth of (CH3NH3)Pb(I,Cl)3 perovskite thin films with the vacuum-based coevaporation approach using two sources under varying deposition conditions. With in situ X-ray diffraction, crystalline phases can be identified and monitored in real time. For different (CH3NH3)I-to-PbCl2 flux ratios, two distinct (CH3NH3)Pb(IxCl(1-x))3 phases with high (x > 0.95) and with lower (x < 0.5) iodine content as well as a broad miscibility gap in-between were found. During post deposition annealing we observe recrystallization and preferential orientation effects and finally the decomposition of the perovskite film to PbI2 at temperatures above 200 degrees C. PMID- 26278438 TI - New Horizons for Conventional Lithium Ion Battery Technology. AB - Secondary lithium ion battery technology has made deliberate, incremental improvements over the past four decades, providing sufficient energy densities to sustain a significant mobile electronic device industry. Because current battery systems provide ~100-150 km of driving distance per charge, ~5-fold improvements are required to fully compete with internal combustion engines that provide >500 km range per tank. Despite expected improvements, the authors believe that lithium ion batteries are unlikely to replace combustion engines in fully electric vehicles. However, high fidelity and safe Li ion batteries can be used in full EVs plus range extenders (e.g., metal air batteries, generators with ICE or gas turbines). This perspective article describes advanced materials and directions that can take this technology further in terms of energy density, and aims at delineating realistic horizons for the next generations of Li ion batteries. This article concentrates on Li intercalation and Li alloying electrodes, relevant to the term Li ion batteries. PMID- 26278439 TI - Silicon Nanocrystals Functionalized with Pyrene Units: Efficient Light-Harvesting Antennae with Bright Near-Infrared Emission. AB - Pyrene chromophores were attached to silicon nanocrystals (SiNCs) with diameters of 2.6 and 5.0 nm to provide light-harvesting antennae for enhanced optical absorption. Efficient energy transfer from the pyrene moieties to the SiNCs was observed to induce bright visible (2.6 nm) or near-infrared (NIR) (5.0 nm) photoluminescence (PL). The 5.0 nm diameter pyrene-derivatized SiNCs exhibited NIR PL emission that was insensitive to dioxygen, with a 40% quantum yield and long lifetime (hundreds of MUs). PMID- 26278440 TI - On the Solar to Hydrogen Conversion Efficiency of Photoelectrodes for Water Splitting. PMID- 26278441 TI - Direct Observation of Ferroelectric Domains in Solution-Processed CH3NH3PbI3 Perovskite Thin Films. AB - A new generation of solid-state photovoltaics is being made possible by the use of organometal-trihalide perovskite materials. While some of these materials are expected to be ferroelectric, almost nothing is known about their ferroelectric properties experimentally. Using piezoforce microscopy (PFM), here we show unambiguously, for the first time, the presence of ferroelectric domains in high quality beta-CH3NH3PbI3 perovskite thin films that have been synthesized using a new solution-processing method. The size of the ferroelectric domains is found to be about the size of the grains (~100 nm). We also present evidence for the reversible switching of the ferroelectric domains by poling with DC biases. This suggests the importance of further PFM investigations into the local ferroelectric behavior of hybrid perovskites, in particular in situ photoeffects. Such investigations could contribute toward the basic understanding of photovoltaic mechanisms in perovskite-based solar cells, which is essential for the further enhancement of the performance of these promising photovoltaics. PMID- 26278442 TI - Monitoring Cocrystal Formation via In Situ Solid-State NMR. AB - A detailed understanding of the mechanism of organic cocrystal formation remains elusive. Techniques that interrogate a reacting system in situ are preferred, though experimentally challenging. We report here the results of a solid-state in situ NMR study of the spontaneous formation of a cocrystal between a pharmaceutical mimic (caffeine) and a coformer (malonic acid). Using (13)C magic angle spinning NMR, we show that the formation of the cocrystal may be tracked in real time. We find no direct evidence for a short-lived, chemical shift-resolved amorphous solid intermediate. However, changes in the line width and line center of the malonic acid methylene resonance, in the course of the reaction, provide subtle clues to the mode of mass transfer that underlies cocrystal formation. PMID- 26278443 TI - Maximizing Singlet Fission by Intermolecular Packing. AB - A novel nonadiabatic molecular dynamics scheme is applied to study the singlet fission (SF) process in pentacene dimers as a function of longitudinal and lateral displacements of the molecular backbones. Detailed two-dimensional mappings of both instantaneous and long-term triplet yields are obtained, characterizing the advantageous and unfavorable stacking arrangements, which can be achieved by chemical substitutions to the bare pentacene molecule. We show that the SF rate can be increased by more than an order of magnitude through tuning the intermolecular packing, most notably when going from cofacial to the slipped stacked arrangements encountered in some pentacene derivatives. The simulations indicate that the SF process is driven by thermal electron-phonon fluctuations at ambient and high temperatures, expected in solar cell applications. Although charge-transfer states are key to construct continuous channels for SF, a large charge-transfer character of the photoexcited state is found to be not essential for efficient SF. The reported time domain study mimics directly numerous laser experiments and provides novel guidelines for designing efficient photovoltaic systems exploiting the SF process with optimum intermolecular packing. PMID- 26278444 TI - Maximum Theoretical Efficiency Limit of Photovoltaic Devices: Effect of Band Structure on Excited State Entropy. AB - The Shockley-Queisser analysis provides a theoretical limit for the maximum energy conversion efficiency of single junction photovoltaic cells. But besides the semiconductor bandgap no other semiconductor properties are considered in the analysis. Here, we show that the maximum conversion efficiency is limited further by the excited state entropy of the semiconductors. The entropy loss can be estimated with the modified Sackur-Tetrode equation as a function of the curvature of the bands, the degeneracy of states near the band edges, the illumination intensity, the temperature, and the band gap. The application of the second law of thermodynamics to semiconductors provides a simple explanation for the observed high performance of group IV, III-V, and II-VI materials with strong covalent bonding and for the lower efficiency of transition metal oxides containing weakly interacting metal d orbitals. The model also predicts efficient energy conversion with quantum confined and molecular structures in the presence of a light harvesting mechanism. PMID- 26278445 TI - Wobbling and Hopping: Studying Dynamics of CO2 Adsorbed in Metal-Organic Frameworks via (17)O Solid-State NMR. AB - Knowledge of adsorbed gas dynamics within microporous solids is crucial for the design of more efficient gas capture materials. We demonstrate that (17)O solid state NMR (SSNMR) experiments allow one to obtain accurate information on CO2 dynamics within metal-organic frameworks (MOFs), using CPO-27-M (M = Mg, Zn) as examples. Variable-temperature (VT) (17)O SSNMR spectra acquired from 150 to 403 K yield key parameters defining the CO2 motions. VT (17)O SSNMR spectra of CPO-27 Zn indicate relatively weaker metal-oxygen binding and increased CO2 dynamics. (17)O SSNMR is a sensitive probe of CO2 dynamics due to the presence of both the quadrupolar and chemical shielding interactions, and holds potential for the investigation of motions within a variety of microporous materials. PMID- 26278446 TI - Broad-Band DREAM Recoupling Sequence. AB - We describe a more broad-banded version of the DREAM double-quantum dipolar recoupling sequence, which is devised by superimposing a phase-alternating RF irradiation scheme, that is, XiX pulses, on top of the original DREAM sequence. We call this sequence XiX(CW) DREAM. The recoupling conditions and the corresponding first-order effective Hamiltonian are analyzed using triple-mode Floquet theory. The performance of the XiX(CW) DREAM sequence is compared to the original DREAM sequence by numerical simulations and experiments on small model substances and the model protein ubiquitin. The results confirm that XiX(CW) DREAM shows a wider recoupling bandwidth compared to that of DREAM, therefore making the choice for the position of the carrier frequency less critical. PMID- 26278447 TI - Vibrational Energy Relaxation of Thiocyanate Ions in Liquid-to-Supercritical Light and Heavy Water. A Fermi's Golden Rule Analysis. AB - The vibrational relaxation dynamics following an ultrafast nitrile stretching (nu3) excitation of thiocyanate anions dissolved in light and heavy water have been studied over a wide temperature and density range corresponding to the aqueous liquid up to the supercritical phase. In both solvents, the relaxation of the nu3 = 1 state of the anion leads to a direct recovery of the vibrational ground state and involves the resonant transfer of the excess vibrational energy onto the solvent. In light water, the energy-accepting states are provided by the bending-librational combination band (nub + nuL), while in heavy water, the relaxation is thermally assisted by virtual acceptor states derived from the stretching-librational/restricted translational hot band (nuS - nuL,T). The relaxation rate is found to strictly obey Fermi's Golden Rule when the density of resonant solvent states is estimated from the linear infrared spectra of the solute and the pure solvents. PMID- 26278448 TI - Hydrogen Dissociation, Spillover, and Desorption from Cu-Supported Co Nanoparticles. AB - Co-Cu nanoparticles have recently been explored for Fischer-Tropsch synthesis (FTS) as a way to combine the long chain selectivity of Co with Cu's activity for alcohol formation in order to synthesize oxygenated transportation fuels. Depending on particle size, hydrogen dissociation can be a rate-determining step in cobalt-catalyzed FTS. To understand the fundamentals of uptake and release of hydrogen from the Co/Cu bimetallic system, we prepared well-defined Co nanoparticles on Cu(111). We demonstrate that hydrogen spills over from dissociation sites on the Co nanoparticles to the Cu(111) surface via the Co-Cu interface and that desorption of H occurs at a temperature that is lower than from Co or Cu alone, which we attribute to the Co-Cu interface sites. From this data, we have constructed an energy landscape for the facile dissociation, spillover, and desorption of hydrogen on the Co-Cu bimetallic system. PMID- 26278449 TI - Ultrafast Photoinduced Electron Transfer in a pi-Conjugated Oligomer/Porphyrin Complex. AB - Controlling charge transfer (CT), charge separation (CS), and charge recombination (CR) at the donor-acceptor interface is extremely important to optimize the conversion efficiency in solar cell devices. In general, ultrafast CT and slow CR are desirable for optimal device performance. In this Letter, the ultrafast excited-state CT between platinum oligomer (DPP-Pt(acac)) as a new electron donor and porphyrin as an electron acceptor is monitored for the first time using femtosecond (fs) transient absorption (TA) spectroscopy with broad band capability and 120 fs temporal resolution. Turning the CT on/off has been shown to be possible either by switching from an organometallic oligomer to a metal-free oligomer or by controlling the charge density on the nitrogen atom of the porphyrin meso unit. Our time-resolved data show that the CT and CS between DPP-Pt(acac) and cationic porphyrin are ultrafast (approximately 1.5 ps), and the CR is slow (ns time scale), as inferred from the formation and the decay of the cationic and anionic species. We also found that the metallic center in the DPP Pt(acac) oligomer and the positive charge on the porphyrin are the keys to switching on/off the ultrafast CT process. PMID- 26278450 TI - Introducing Article Transfer from Letters to Regular Articles. PMID- 26278451 TI - Evidence for the Formation of Pyrimidine Cations from the Sequential Reactions of Hydrogen Cyanide with the Acetylene Radical Cation. AB - Herein, we report the first direct evidence for the formation of pyrimidine ion isomers by sequential reactions of HCN with the acetylene radical cation in the gas phase at ambient temperature using the mass-selected variable temperature and pressure ion mobility technique. The formation and structures of the pyrimidine ion isomers are theoretically predicted via coupled cluster and density functional theory calculations. This ion-molecule synthesis may indicate that pyrimidine is produced in the gas phase in space environments before being incorporated into condensed-phase ices and transformed into nucleic acid bases such as uracil. PMID- 26278452 TI - X-ray Photoelectron Spectroscopy of Isolated Nanoparticles. AB - X-ray photoelectron spectroscopy (XPS) is a very efficient and still progressing surface analysis technique. However, when applied to nano-objects, this technique faces drawbacks due to interactions with the substrate and sample charging effects. We present a new experimental approach to XPS based on coupling soft X ray synchrotron radiation with an in-vacuum beam of free nanoparticles, focused by an aerodynamic lens system. The structure of the Si/SiO2 interface was probed without any substrate interaction or charging effects for silicon nanocrystals previously oxidized in ambient air. Complete characterization of the surface was obtained. The Si 2p core level spectrum reveals a nonabrupt interface. PMID- 26278453 TI - Infrared Pump-Probe Study of Nanoconfined Water Structure in Reverse Micelle. AB - The influence of nanoconfinement on water structure is studied with time- and frequency-resolved vibrational spectroscopy of hydrazoic acid (HN3) encapsulated in reverse micelle. The azido stretch mode of HN3 is found to be a promising infrared probe for studying the structure and local hydrogen-bond environment of confined and interfacial water in reverse micelle due to its narrow spectral bandwidth and large transition dipole moment. The results show a clear separation between the core and shell spectral components, making it advantageous over the previously studied infrared probes. The measured vibrational lifetimes appear to be substantially different for the interfacial and bulk-like environments but show no remarkable size dependency, which indicates that water structures around this IR probe are distinctively different in the core and shell regions. The influence of local hydrogen bond network in the first and higher solvation shells on the vibrational dynamics of HN3 is further discussed. PMID- 26278454 TI - Theoretical Model of Oxidative Adsorption of Water on a Highly Reduced Reconstructed Oxide Surface. AB - Highly reduced surface reconstructions of BaTiO3 (001) have been found to be composed of a TiO2 surface covered with Ti adatoms occupying surface interstitial sites. We predict the reactivity of these highly oxophilic and reduced surface Ti species through density functional theory, where we calculate the adsorption of H2O on the (?5 * ?5)R26.6 degrees TiO2-Ti3/5 reconstruction. H2O serves as the primary O source and oxidizing agent. We demonstrate that H2O oxidizes some of the Ti adatoms, shifting their occupied 3d states to the surface conduction band edge. We find that, due to the high concentration of reduced Ti species on the surface, a dissociative adsorption of water on the reconstructed surface can also lead to the formation of surface hydrides, which serve as a precursor for H2 evolution. This suggests that the reconstructed surface may be an attractive single-phase hydrogen evolution catalyst. PMID- 26278455 TI - Exploding Nitromethane in Silico, in Real Time. AB - Nitromethane (NM) is widely applied in chemical technology as a solvent for extraction, cleaning, and chemical synthesis. NM was considered safe for a long time, until a railroad tanker car exploded in 1958. We investigate the detonation kinetics and explosion reaction mechanisms in a variety of systems consisting of NM, molecular oxygen, and water vapor. Reactive molecular dynamics allows us to simulate reactions in time-domain, as they occur in real life. High polarity of the NM molecule is shown to play a key role, driving the first exothermic step of the reaction. Rapid temperature and pressure growth stimulate the subsequent reaction steps. Oxygen is important for faster oxidation, whereas its optimal concentration is in agreement with the proposed reaction mechanism. Addition of water (50 mol %) inhibits detonation; however, water does not prevent detonation entirely. The reported results provide important insights for improving applications of NM and preserving the safety of industrial processes. PMID- 26278456 TI - Highly Efficient Polarization of Spin-1/2 Insensitive NMR Nuclei by Adiabatic Passage through Level Anticrossings. AB - A method is proposed to transfer spin order from para-hydrogen, that is, the H2 molecule in its singlet state, to spin-1/2 heteronuclei of a substrate molecule. The method is based on adiabatic passage through nuclear spin level anticrossings (LACs) in the doubly rotating frame of reference; the LAC conditions are fulfilled by applying resonant RF excitation at the NMR frequencies of protons and the heteronuclei. Efficient conversion of the para-hydrogen-induced polarization into net polarization of the heteronuclei is demonstrated; the achieved signal enhancements are about 6400 for (13)C nuclei at natural abundance. The theory behind the technique is described; advantages of the method are discussed in detail. PMID- 26278457 TI - Influence of Molecular Shape on Solid-State Packing in Disordered PC61BM and PC71BM Fullerenes. AB - Molecular and polymer packings in pure and mixed domains and at interfacial regions play an important role in the photoconversion processes occurring within bulk heterojunction organic solar cells (OSCs). Here, molecular dynamics simulations are used to investigate molecular packing in disordered (amorphous) phenyl-C70-butyric acid-methyl ester (PC71BM) and its C60 analogue (PC61BM), the two most widely used molecular-based electron-accepting materials in OSCs. The more ellipsoidal character of PC71BM leads to different molecular packings and phase transitions when compared to the more spherical PC61BM. Though electronic structure calculations indicate that the average intermolecular electronic couplings are comparable for the two systems, the electronic couplings as a function of orientation reveal important variations. Overall, this work highlights a series of intrinsic differences between PC71BM and PC61BM that should be considered for a detailed interpretation and modeling of the photoconversion process in OSCs where these materials are used. PMID- 26278458 TI - Correction to "Parameters Affecting I-V Hysteresis of CH3NH3PbI3 Perovskite Solar Cells: Effects of Perovskite Crystal Size and Mesoporous TiO2 Layer". PMID- 26278459 TI - Correction to "On Universality in Sputtering Yields Due to Cluster Bombardment". PMID- 26278460 TI - Polydopamine Films from the Forgotten Air/Water Interface. AB - The formation of polydopamine under mild oxidation conditions from dopamine solutions with mechanical agitation leads to the formation of films that can functionalize all kinds of materials. In the absence of stirring of the solution, we report the formation of polydopamine films at the air/water interface (PDA A/W) and suggest that it arises from an homogeneous nucleation process. These films grow two times faster than in solution and can be deposited on hydrophilic or hydrophobic substrates by the Langmuir-Schaeffer technique. Thanks to this new method, porous and hydrophobic materials like polytetrafluoroethylene (PTFE) membranes can be completely covered with a 35 nm thick PDA A/W film after only 3h of reaction. Finally the oxidation of a monomer followed by a polymerization in water is not exclusive to polydopamine since we also transferred polyaniline functional films from the air/water interface to solid substrates. These findings suggest that self-assembly from a solution containing hydrophilic monomers undergoing a chemical transformation (here oxidation and oligomerization) could be a general method to produce films at the liquid/air interface. PMID- 26278461 TI - Dimerization Induced Deprotonation of Water on RuO2(110). AB - RuO2 has proven to be indispensable as a co-catalyst in numerous systems designed for photocatalytic water splitting. In this study, we have carried out a detailed mechanistic study of water behavior on the most stable RuO2 face, RuO2(110), by employing variable-temperature scanning tunneling microscopy and density functional theory calculations. We show that water monomers adsorb molecularly on Ru sites, become mobile above 238 K, diffuse along the Ru rows, and form water dimers. The onset for dimer diffusion is observed at ~277 K, indicating a significantly higher diffusion barrier than that for monomers. More importantly, we find that water dimers deprotonate readily to form Ru-bound H3O2 and bridging OH species. The observed behavior is compared and contrasted with that observed for water on isostructural rutile TiO2(110). PMID- 26278463 TI - Risk for Nonalcoholic Fatty Liver Disease in Young Adults Born Preterm. AB - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. Accelerated catch-up in weight during infancy in subjects born at full term has been associated with increased risk for NAFLD in adulthood, but this association has not been studied in subjects born preterm. METHODS: In 162 young adults born at a gestational age <36 weeks, we assessed the associations between fatty liver index (FLI, 0-100) and birth weight standard deviation score and first-year weight gain. We performed comparisons between subjects with and without accelerated catch-up in weight in the first year after term age. An FLI score was assigned to each participant to determine the clinical relevance, and regression analyses were performed. RESULTS: Accelerated weight gain in the first 3 months after term age was associated with FLI as a continuous variable, whereas gestational age and low birth weight were not. Of the subjects with accelerated catch-up in weight-for-length after term age, 7.3% had a high FLI at the age of 21 years, whereas none of the subjects without accelerated catch-up in weight had a high FLI. CONCLUSION: Our study shows that accelerated weight gain after term age is associated with an increased risk of developing NAFLD in young adults born preterm. PMID- 26278462 TI - Novel Therapeutic Options for the Treatment of Mineral Metabolism Abnormalities in End Stage Renal Disease. AB - Abnormalities in mineral metabolism are a universal complication in dialysis patients and are associated with an increased risk of cardiovascular disease and mortality. Hyperphosphatemia, increased fibroblast growth factor 23 levels and secondary hyperparathyroidism are all strongly associated with adverse outcomes in end stage renal disease (ESRD) and most treatment strategies target these parameters. Over the past few years, new therapies have emerged for the treatment of abnormalities of mineral metabolism in ESRD and many are promising. This article will review these new therapeutic options including the potential advantages and disadvantages compared to existing therapies. PMID- 26278464 TI - Association of gastrointestinal events and osteoporosis treatment initiation in newly diagnosed osteoporotic Israeli women. AB - BACKGROUND: The objective was to examine the association of gastrointestinal (GI) events and osteoporosis treatment initiation patterns among postmenopausal women following an osteoporosis diagnosis from an Israeli health plan. METHODS: This retrospective analysis of claims records included women aged >= 55 years with >= 1 osteoporosis diagnosis (date of first diagnosis was index date). Osteoporosis treatment initiation was defined as use of osteoporosis therapy (oral bisphosphonates or other) during 12 months postindex. GI events (diagnosis of GI conditions) were reported for 12 months preindex and postindex (from index to treatment initiation or 1 year postindex, whichever occurred first). The association of postindex GI events (yes/no) with the initiation of osteoporosis treatment (yes/no) and with type of therapy initiated (oral bisphosphonate vs. other) were examined with logistic regression and Cox proportional hazard regression (as sensitivity analysis). RESULTS: Among 30,788 eligible patients, 17.5% had preindex GI events and 13.0% had postindex GI events. About 70.6% of patients received no osteoporosis therapy within 1 year of diagnosis, 24.9% received oral bisphosphonates and 4.5% received other medications. Postindex GI events were associated with lower odds of osteoporosis medication initiation (85 86% reduced likelihood; p < 0.01). Upon treatment initiation, postindex GI was not significantly associated with the type of osteoporosis therapy initiated, controlling for baseline GI events and patient characteristics. CONCLUSIONS: Among newly diagnosed osteoporotic women from a large Israeli health plan, 70.6% did not receive osteoporosis treatment within 1 year of diagnosis. The presence of GI events was associated with reduced likelihood of osteoporosis treatment initiation. PMID- 26278465 TI - Crystal structure of 3-acetyl-4H-chromen-4-one. AB - In the title compound, C11H8O3, the fused-ring system is almost planar (r.m.s. deviation = 0.020 A), with the largest deviation from the least-squares plane [0.0462 (17) A] being for a pyran C atom. The dihedral angle between the plane of the fused-ring system and acetyl plane is 5.149 (16) degrees . In the crystal, the fused rings are linked by aromatic pi-pi stacking inter-actions [centroid centroid distance between the benzene and pyran rings = 3.643 (6) A] and C-H?O hydrogen bonds, generating a three-dimensional network. PMID- 26278466 TI - Machine Learning methods for Quantitative Radiomic Biomarkers. AB - Radiomics extracts and mines large number of medical imaging features quantifying tumor phenotypic characteristics. Highly accurate and reliable machine-learning approaches can drive the success of radiomic applications in clinical care. In this radiomic study, fourteen feature selection methods and twelve classification methods were examined in terms of their performance and stability for predicting overall survival. A total of 440 radiomic features were extracted from pre treatment computed tomography (CT) images of 464 lung cancer patients. To ensure the unbiased evaluation of different machine-learning methods, publicly available implementations along with reported parameter configurations were used. Furthermore, we used two independent radiomic cohorts for training (n = 310 patients) and validation (n = 154 patients). We identified that Wilcoxon test based feature selection method WLCX (stability = 0.84 +/- 0.05, AUC = 0.65 +/- 0.02) and a classification method random forest RF (RSD = 3.52%, AUC = 0.66 +/- 0.03) had highest prognostic performance with high stability against data perturbation. Our variability analysis indicated that the choice of classification method is the most dominant source of performance variation (34.21% of total variance). Identification of optimal machine-learning methods for radiomic applications is a crucial step towards stable and clinically relevant radiomic biomarkers, providing a non-invasive way of quantifying and monitoring tumor-phenotypic characteristics in clinical practice. PMID- 26278467 TI - Deviant patterns of methylphenidate use in adults: a Danish nationwide registry based drug utilization study. AB - PURPOSE: Several survey studies have documented misuse of methylphenidate defined as the use of non-prescribed methylphenidate or use different from what was prescribed. We aimed to identify and characterize adults with deviant patterns of methylphenidate use in Denmark during 2007-2012. Further, we aimed to identify risk factors associated with deviant patterns of use. METHODS: Based on individual-level prescription data, new users of methylphenidate were followed for one year after filling their first prescription on methylphenidate. Adult patients were identified with deviant patterns of use if they had >=4 different prescribers and filled >=1095 defined daily doses of methylphenidate during the year of follow-up. Risk factors were estimated by using logistic regression. RESULTS: Among 20 829 new users of methylphenidate, we identified 82 (0.39%) patients displaying deviant patterns of use. Characteristics associated with deviant patterns of use included an initial prescription for extended-release methylphenidate (OR2 4.35), age 25-49 years at first prescription (OR2 2.49), general practitioners or hospital doctors as initial prescribers (OR2 3.06 and OR2 4.07) and prior use of drugs used in addictive disorders (OR2 2.08) or opioids (OR2 1.75). Sensitivity analyses revealed that the number of different prescribers alone does not seem to effectively identify deviant users of methylphenidate. CONCLUSION: We have identified characteristics associated with deviant patterns of methylphenidate use. Our results do not allow us to conclude if deviant users truly represent medical misusers. PMID- 26278468 TI - Synthesis of cubic ZnS microspheres exhibiting broad visible emission for bioimaging applications. AB - Biocompatible ZnS microspheres with an average diameter of 3.85 um were grown by solvo-hydrothermal (S-H) method using water-acetonitrile-ethylenediamine (EDA) solution combination. ZnS microspheres were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), Fourier transform (FT)-Raman spectroscopy and Fourier transform infrared spectroscopy (FTIR) techniques. The broad photoluminescence (PL) emissions from 380-580 nm that were seen from the ZnS microspheres attributed to the increase in carrier concentration, as understood from the observed intense Raman band at 257 cm(-1). Cytotoxicity and haemocompatibility investigations of these ZnS microspheres revealed its biocompatibility. ZnS microspheres, along with biological cell lines, were giving visible light emission and could be used for bioimaging applications. PMID- 26278470 TI - Inference-Based Approach versus Cognitive Behavioral Therapy in the Treatment of Obsessive-Compulsive Disorder with Poor Insight: A 24-Session Randomized Controlled Trial. AB - OBJECTIVE: Obsessive-compulsive disorder (OCD) with poor insight has severe consequences for patients; nonetheless, no randomized controlled trial has ever been performed to evaluate the effectiveness of any treatment specifically for poor-insight OCD. A new psychotherapy for OCD, the inference-based approach (IBA), targets insight in OCD by strengthening normal sensory-driven reality testing. The goal of the present study is to compare the effectiveness of this new treatment to the effectiveness of cognitive behavior therapy (CBT) for patients with OCD with poor insight. METHOD: A randomized controlled trial was conducted, in which 90 patients with OCD with poor insight received either 24 CBT sessions or 24 IBA sessions. The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale (YBOCS). Secondary outcome measures were level of insight, anxiety and depressive symptoms, and quality of life. Mixed-effects models were used to determine the treatment effect. RESULTS: In both conditions, a significant OCD symptom reduction was reached, but no condition effects were established. Post hoc, in a small subgroup of patients with the worst insight (n = 23), it was found that the patients treated with the IBA reached a significantly higher OCD symptom reduction than the patients treated with CBT [estimated marginal mean = -7.77, t(219.45) = -2.4, p = 0.017]. CONCLUSION: Patients with OCD with poor insight improve significantly after psychological treatment. The results of this study suggest that both CBT and the IBA are effective treatments for OCD with poor insight. The IBA might be more promising than CBT for patients with more extreme poor insight. PMID- 26278469 TI - Sperm navigation along helical paths in 3D chemoattractant landscapes. AB - Sperm require a sense of direction to locate the egg for fertilization. They follow gradients of chemical and physical cues provided by the egg or the oviduct. However, the principles underlying three-dimensional (3D) navigation in chemical landscapes are unknown. Here using holographic microscopy and optochemical techniques, we track sea urchin sperm navigating in 3D chemoattractant gradients. Sperm sense gradients on two timescales, which produces two different steering responses. A periodic component, resulting from the helical swimming, gradually aligns the helix towards the gradient. When incremental path corrections fail and sperm get off course, a sharp turning manoeuvre puts sperm back on track. Turning results from an 'off' Ca(2+) response signifying a chemoattractant stimulation decrease and, thereby, a drop in cyclic GMP concentration and membrane voltage. These findings highlight the computational sophistication by which sperm sample gradients for deterministic klinotaxis. We provide a conceptual and technical framework for studying microswimmers in 3D chemical landscapes. PMID- 26278471 TI - Review of human hand microbiome research. AB - Recent advances have increased our understanding of the human microbiome, including the skin microbiome. Despite the importance of the hands as a vector for infection transmission, there have been no comprehensive reviews of recent advances in hand microbiome research or overviews of the factors that influence the composition of the hand microbiome. A comprehensive and systematic database search was conducted for skin microbiome-related articles published from January 1, 2008 to April 1, 2015. Only primary research articles that used culture independent, whole community analysis methods to study the healthy hand skin microbiome were included. Eighteen articles were identified containing hand microbiome data. Most focused on bacteria, with relatively little reported on fungi, viruses, and protozoa. Bacteria from four phyla were found across all studies of the hand microbiome (most to least relative abundance): Firmicutes, Actinobacteria, Proteobacteria, Bacteroidetes. Key factors that impacted the hand microbiome composition included temporal and biogeographical dynamics, as well as intrinsic (age, gender) and extrinsic (product use, cohabitants, pet-ownership) variables. There was more temporal variability in the composition of the hand microbiome than in other body sites, making identification of the "normal" microbiome of the hands challenging. The microbiome of the hands is in constant flux as the hands are a critical vector for transmitting microorganisms between people, pets, inanimate objects and our environments. Future studies need to resolve methodological influences on results, and further investigate factors which alter the hand microbiome including the impact of products applied to hands. Increased understanding of the hand microbiome and the skin microbiome in general, will open the door to product development for disease prevention and treatment, and may lead to other applications, including novel diagnostic and forensic approaches. PMID- 26278473 TI - Awareness of rabies prevention and control measures among public health workers in Northern Vietnam. AB - OBJECTIVES: To assess and compare rabies related knowledge and awareness of public health workers at provincial and district levels in the seven provinces with the highest number of deaths from human rabies in northern Vietnam. STUDY DESIGN: A cross-sectional study. METHOD: A survey was administered to a convenience sample of public health workers attending four workshops on rabies disease, control and prevention between 16 October and 21 November, 2012. Total knowledge scores (maximum 38 points) were categorized into: 'high' (>30 points) 'moderate' (21-30) and 'low' (<21). The Chi-square test was used to evaluate the statistical significance of the differences in responses between the respondents. RESULTS: Of the 105 public health workers attending the workshops: 57% were male; 76% worked at the district level compared with 24% who worked at provincial level; and 45% had worked in rabies control for <1 year compared with 11% who had worked in rabies control for >5 years. Overall knowledge was patchy and ranked as 'moderate'. Important gaps in knowledge were identified particularly in relation to indications for rabies vaccine and rabies immunoglobulin, and routes of exposure to rabies virus. One in ten respondents did not know that rabies virus could be transmitted by the bite of an infected animal. When examining the overall mean knowledge scores, marginally significant differences were identified. The average scores for district level health workers (DLHW) and provincial level health workers (PLHW) were 28 +/- 3 and 29 +/- 3 points respectively (p = 0.098), which fell within the study definition of 'moderate' knowledge. In contrast, when 'high' knowledge scores were compared, a significantly greater proportion of PLHW achieved >30 points compared to DLHW (44.0% vs 22.5%, p = 0.044). CONCLUSIONS: Important gaps in knowledge and awareness of public health workers were identified particularly in relation to routes of exposure to rabies virus and indications for rabies vaccine and rabies immunoglobulin. Overall, comparison of knowledge scores revealed significant differences between district and provincial public health workers. The results obtained suggest that in order for rabies control programmes to succeed public health workers at all levels need to have accurate and evidence-based knowledge. This may be facilitated by improving the quantity and quality of their training and education. PMID- 26278472 TI - Predicting lncRNA-disease associations and constructing lncRNA functional similarity network based on the information of miRNA. AB - Accumulating experimental studies have indicated that lncRNAs play important roles in various critical biological process and their alterations and dysregulations have been associated with many important complex diseases. Developing effective computational models to predict potential disease-lncRNA association could benefit not only the understanding of disease mechanism at lncRNA level, but also the detection of disease biomarkers for disease diagnosis, treatment, prognosis and prevention. However, known experimentally confirmed disease-lncRNA associations are still very limited. In this study, a novel model of HyperGeometric distribution for LncRNA-Disease Association inference (HGLDA) was developed to predict lncRNA-disease associations by integrating miRNA-disease associations and lncRNA-miRNA interactions. Although HGLDA didn't rely on any known disease-lncRNA associations, it still obtained an AUC of 0.7621 in the leave-one-out cross validation. Furthermore, 19 predicted associations for breast cancer, lung cancer, and colorectal cancer were verified by biological experimental studies. Furthermore, the model of LncRNA Functional Similarity Calculation based on the information of MiRNA (LFSCM) was developed to calculate lncRNA functional similarity on a large scale by integrating disease semantic similarity, miRNA-disease associations, and miRNA-lncRNA interactions. It is anticipated that HGLDA and LFSCM could be effective biological tools for biomedical research. PMID- 26278474 TI - Partnerships for community resilience: perspectives from the Los Angeles County Community Disaster Resilience project. PMID- 26278475 TI - Effects of three interventions and determinants of full vaccination among children aged 12-59 months in Nyanza province, Kenya. AB - OBJECTIVES: The purpose of this study is to describe the effects of the three main interventions and identify the individual and community determinants of full vaccination coverage among children aged 12-59 months in Nyanza province, Kenya. STUDY DESIGN: Cross-sectional study. METHODS: We utilized three datasets. One is the Nyanza Province County-based Multiple Indicator Cluster Survey 2011. The other two datasets are the lists of community units and health facilities in Nyanza Province, Kenya. A three-level multilevel logistic regression analysis was performed. RESULTS: In the final model, the highest wealth quintile (AOR: 2.49; 95% CI: 1.333-4.642; P = 0.004), the community with high coverage of media devices (AOR: 1.50; 95% CI: 1.029-2.198; P = 0.035), the participation of mass immunization campaigns (AOR: 1.63; 95% CI: 1.153-2.303; P = 0.006) were the significant determinants of complete child vaccination. CONCLUSIONS: In conclusion, further implementation of mass immunization campaigns is the recommended intervention to increase the uptake of required vaccinations among children. In addition, further attention to the poor and the low coverage of media devices is necessary, since they are the most vulnerable population in terms of accessibility of vaccination services. Implementation community based activity, such as community health workers, would have a positive impact on vaccination coverage, if their performance is continuously high. PMID- 26278477 TI - Prevalence and covariates of food insecurity among residents of single-room occupancy housing in Chicago, IL, USA. AB - OBJECTIVE: Emerging evidence suggests that food insecurity is a significant public health concern among people who are homeless or marginally housed. The present study assessed prevalence of food insecurity and its covariates among a group of marginally housed individuals living in single-room occupancy (SRO) dwellings, a population for which there is little extant health or nutrition research. DESIGN: Cross-sectional survey incorporating the Household Food Insecurity Access Scale. SETTING: Ten private SRO residences in the Uptown neighbourhood of Chicago, IL, USA, 2013. SUBJECTS: SRO residents over 18 years of age who were able to communicate verbally in English (n 153). RESULTS: Food insecurity was widespread among SRO residents, with 75 % of the sample considered food insecure and 52 % meeting criteria for severe food insecurity. Bivariate analyses indicated that female gender, eating most meals at a soup kitchen, having a mental health condition, problem drinking, having at least one chronic health condition, and diabetes were all significantly associated with food insecurity. In the multivariate ordered logistic regression model, eating most meals at a soup kitchen remained as the only significant correlate of food insecurity (OR=10.13). CONCLUSIONS: SRO residents and other marginally housed populations face unique food access challenges. Although targeted assistance in the form of food stamps and congregate meal programmes remains critical, efforts to prevent and address food insecurity among homeless and marginally housed individuals should include policy interventions that recognize poverty as the root cause of food insecurity and aim to increase overall income and improve housing conditions. PMID- 26278476 TI - Supporting general practices to provide sexual and reproductive health services: protocol for the 3Cs & HIV programme. AB - OBJECTIVES: Sexually transmitted infections, HIV and unplanned pregnancies continue to be a major public health problem in England, especially in young adults. Strengthening the provision of free condoms, HIV testing, chlamydia screening and contraception within primary care will contribute to reducing poor sexual and reproductive health outcomes. Recent research demonstrated the benefit for general practices of educational support visits based on behaviour change theory. Public Health England (PHE) has piloted an educational training programme to improve the delivery of sexual health services and HIV testing within general practice. STUDY DESIGN & METHODS: The 3Cs & HIV programme used practice based workshops to improve staffs' awareness and skills in order to increase opportunistic offers of chlamydia testing, provision of contraceptive service information and free condoms (the '3Cs') to 15-24 year olds and HIV testing according to national guidelines. The programme was based on the theory of planned behaviour and has been implemented using a stepped wedge design. Process evaluation, testing and diagnosis data, plus qualitative interviews were all used in the evaluation. The primary outcome measures were chlamydia testing and diagnosis rates. Secondary outcome measures were HIV testing and diagnoses rates within each practice and rates of consultations where long acting reversible contraceptives had been discussed. CONCLUSION: A key strength of the 3Cs & HIV programme has been the evidence base underpinning the development of the resources and the formal process evaluation of its implementation. The programme was designed to encourage sustainable relationships between general practice staff and local sexual health services as well as the knowledge, awareness and behaviours cultivated during the programme. PMID- 26278478 TI - Experimental realization of spatially separated entanglement with continuous variables using laser pulse trains. AB - Spatially separated entanglement is demonstrated by interfering two high repetition squeezed pulse trains. The entanglement correlation of the quadrature amplitudes between individual pulses is interrogated. It is characterized in terms of the sufficient inseparability criterion with an optimum result of in the frequency domain and in the time domain. The quantum correlation is also observed when the two measurement stations are separated by a physical distance of 4.5 m, which is sufficiently large to demonstrate the space-like separation, after accounting for the measurement time. PMID- 26278480 TI - [Perioperative management of patients with Parkinson's disease. Review of the literature]. AB - Similarly to an increase in life expectancy, the incidence of Parkinson's disease increases as well. In parallel with this, more patients with Parkinson's disease undergo elective or urgent surgical interventions. According to recent statistical data, more than half of the patients with Parkinson's disease are not properly managed when they are hospitalized for surgical interventions. It is also clear that properly managed Parkinson's disease patients have an approximately 50% lower rate for perioperative complications. The authors aimed to summarize the most important complications, the updated peri- and intraoperative treatment and management strategies of patients with Parkinson's disease. They intended to underline that interdisciplinary cooperation and knowledge of the proper strategy may result in more successful treatment of Parkinson's disease patients during the perioperative period. PMID- 26278479 TI - Functional Ser205Leu polymorphism of the nerve growth factor receptor (NGFR) gene is associated with vagal autonomic dysregulation in humans. AB - Evidence indicates that reduced cardiac vagal (parasympathetic) tone, a robust cardiovascular risk factor, is a trait vulnerability marker of major depressive disorder (MDD). The Ser205/Ser205 genotype of the functional polymorphism (Ser205Leu) of the nerve growth factor receptor (NGFR), also called p75 neurotrophin receptor (p75(NTR)), gene is reported to increase the risk of MDD. Here, we hypothesized that the NGFR Ser205Leu polymorphism may have an effect on vagal control. A sample of 810 healthy, drug-free, unrelated Han Chinese (413 males, 397 females; mean age 35.17 +/- 8.53 years) was included in the NGFR genotyping. Short-term heart rate variability (HRV) was used to assess vagus mediated autonomic function. Potential HRV covariates, such as mood/anxiety status and serum metabolic parameters, were assessed. Homozygotes of the Ser205 allele had significantly lower high frequency power and root mean square of successive heartbeat interval differences, both HRV indices of vagal modulation, compared to Leu205 allele carriers. Even after adjusting for relevant confounders, these associations remained significant. Further stratification by sex revealed that the associations were observed only in males. Our results implicate that decreased parasympathetic activity is associated with the NGFR Ser205/Ser205 genotype in a gender-specific manner, suggesting a potential role of NGFR polymorphism in modulating cardiac autonomic function. PMID- 26278481 TI - [Outcomes of childbearing and pregnancy in women with multiple sclerosis--a literature review]. AB - In the last few years more studies indicated that although sclerosis multiplex frequently manifests in young adulthood, it should not be considered as contraindication for pregnancy in women affected with the disease. In fact, despite controversial literature data, pregnancy appears to be a protective factor to the disease without a harmful effect on the fetus. However, the use of immunomodulatory therapy during pregnancy needs a careful evaluation process and experts of this field may contribute to family happiness of the affected mother. PMID- 26278482 TI - [Bacterial infection after orthotopic liver transplantation]. AB - INTRODUCTION: The authors reviewed the prevalence of postoperative infections, the results of bacterium cultures, and the incidence of multidrug resistance in their liver transplanted patients during a period between 2003 and 2012. AIM: The aim of this study was to analyse risk factors and colonisations of bacterial infections. METHOD: The files of 408 patients (281 bacterium cultures) were reviewed. RESULTS: Of the 408 patients 70 had a postoperative infection (17%); 58 patients (14.2%) had positive and 12 patients (2.9%) negative bacterial culture results. Cholangitis was found in 7 cases (12.1%), abdominal infection in 17 cases (29.3%), and pulmonary infection in 28 cases (48.3%). Postoperative infection was more frequent in patients with initial poor graft function, acute renal insufficiency, biliary complication, and in those with intraabdominal bleeding. The 1-, 3- and 5-year cumulative survival of patients who had infection was 70%, 56% and 56%, respectively, whereas the cumulative survival data of patients without infection was 94%, 87% and 85%, respectively (p<0.001). Multidrug resistance was found in 56% of the positive cultures, however, the one year survival was not different in patients who had multidrug resistance positive and negative bacterial infection (both 70.2%). CONCLUSIONS: Infection control must target the management of multidrug resistance microbes through encouraging prevention, hygienic, and isolation rules, improving the operative, transfusion, and antimicrobial policy in a teamwork setting. PMID- 26278483 TI - [Transfusiology knowledge and competence of nurses in light of a national survey]. AB - INTRODUCTION: International literature data clearly show that the role of nurses in transfusion therapy, which needs professional knowledge and skills, continues to increase. AIM: The aim of the authors was to perform a national-level mapping of the practice of transfusion therapy including transfusion therapy-related knowledge of nurses and their knowledge about their competence. Further aim was to identify similarities and differences as referred to the requirements of the transfusion regulations (2008), which was valid at the time of the survey in Hungary. METHOD: The nationwide survey took place between November 19, 2014 and February 20, 2015. Data were collected using paper-form and web-based anonymous, self-administered questionnaire. 657 nurses who were involved in transfusion therapy with changing regularity in adult in-patient wards took part in the survey. Data were processed using descriptive statistical methods. RESULTS: It was found that the transfusion therapy related knowledge of nurses was very incomplete (50.72%), and only about half of the nurses (52.3%) systematized the nursing functions correctly. Significant differences were also found in the practice of transfusion therapy. The vast majority of the institutions had their own protocol, but responsible nurses assigned for transfusion care were present only in 23.9% of the wards. CONCLUSIONS: The authors conclude that the identified problems can be resolved by improving professional responsibility of nurses, increasing supervision by nursing leaders and appropriate transfusiology training and regular retrainings. PMID- 26278484 TI - Mediterranean diet and childhood asthma. AB - BACKGROUND: The incidence of bronchial hyperreactivity has increased to one-third of the population in developed countries, which requires the adoption of preventive and therapeutic measures. The objective of the present study was to assess the effects of a traditional Mediterranean diet on patients diagnosed with childhood asthma and determine if there is a beneficial effect from this dietary intervention. METHODS: Prospective before-after comparison study of 50 girls and 54 boys aged 1-5 years, who were enrolled in the 1-year programme "Learning to Eat from the Mediterranean", designed to promote the adoption of a traditional Mediterranean diet. We studied the clinical and therapeutic variables and anthropometric measurements. RESULTS: All studied symptomatic indicators (number and intensity of asthmatic attack, infections and hospital admissions) showed a positive and statistically significant evolution of bronchial hyperreactivity from the first weeks of the intervention onwards. Throughout the treatment, 32.2% of patients remained free of crisis, 35.3% of the patients only had one attack throughout the year and 24.9% had two episodes, compared to 4.73 episodes on average in the previous year. The use of inhaled corticosteroids markedly decreased from 3.92 +/- 1.61 to 1.11 +/- 1.09 times per patient per year (P<0.001) and that of inhaled bronchodilators decreased from 4.14 +/- 1.61 to 1.12 +/- 1.40 (P<0.001). As a result, the families involved in the programme reported a high level of satisfaction. CONCLUSIONS: The adoption of a traditional Mediterranean diet could contribute significantly to the improvement of patients diagnosed with childhood asthma. PMID- 26278485 TI - Patient Factors and Cost Associated with 90-Day Readmission Following Total Hip Arthroplasty. AB - This study sought to identify specific costs for 90-day readmissions following total hip arthroplasty in a bundled payment system. Hospital billing records revealed 139 readmissions (8.93%) in 1781 patients. Mean costs for surgical readmissions were greater (P=0.002) compared with medical reasons, but similar for Medicare/Medicaid and private payers (P=0.975). Costs for imaging, laboratory workup, medication and transfusions, and hospital cost correlated with increasing SOI (P<0.05). Patients transferred from outside hospitals or rehabilitation had higher hospital (P=0.006) and operating room costs (P=0.001) compared to patients admitted from ED or clinic. Hospitals that care for complex patients with Medicare/Medicaid may experience increased costs for unplanned 90-day readmissions highlighting considerations for payer mix. PMID- 26278486 TI - Quantifying Gait Quality in Patients with Large-Head and Conventional Total Hip Arthroplasty--A Prospective Cohort Study. AB - We used the Gait Deviation Index (GDI) as method to compare preoperative to postoperative gait changes after uncemented 50 mm (median) large-head and 28/32 mm total hip arthroplasty (THA). We also identified predictors of improvements in GDI. Gait analysis and patient-reported (WOMAC) data were recorded in 35 patients before, 2 and 6-months after treatment. Twenty age-matched adults provided normative gait data. Contrary to our hypothesis, patients who received large-head THA had less improvement in GDI compared with patients who received 28/32 mm THA. The preoperative GDI score was identified as a predictor of postoperative GDI improvement, while WOMAC, age, gender and walking speed were not. This study provides useful information for clinicians and rehabilitation specialists about gait improvement that can be expected after THA. PMID- 26278487 TI - Encapsulation of polyphenols into pHEMA e-spun fibers and determination of their antioxidant activities. AB - This study reports on the development of electrospun poly(2-hydroxyethyl methacrylate) (pHEMA) fibers loaded with synthetic and natural antioxidants in the form of selected types of polyphenols such as vanillic, gallic, syringic acids, catechin or natural spruce bark extract to investigate their release behavior in terms of antioxidant activities. Homogenous fiber morphologies were obtained at specified concentration ranges of pHEMA within the spinning solutions, exhibiting fiber diameters in the range from 0.5+/-0.1 MUm to 1.9+/ 0.5 MUm. The addition of polyphenols resulted in an increase of fiber diameters with increasing concentration of additives. This is attributed to the effect of hydrogen bonding between the active ingredients and the polymeric matrix, increasing shear viscosities and thus hindering effective drawing processes during fiber formation. Polyphenol release measurement gave high release rates in a first phase followed by a smooth release at long term. The 2,2-diphenyl-1 picrylhydrazyl (DPPH) assay, used to monitor antioxidant activity, showed that polyphenols had retained their activity after incorporation into the pHEMA nanofibers. Furthermore, it was demonstrated that the encapsulation of polyphenols in pHEMA nanofibers can delay to a high extent their degradation induced by environmental factors. PMID- 26278488 TI - Migration of plasticizers from PVC medical devices: Development of an infusion model. AB - Alternatives to DEHP plasticizers are used in various PVC medical devices (MD) for infusion. As they are able to migrate from these MDs into infused solutions, they may come into contact with patient. Different and specific clinical parameters influence their migration in at-risk situations such as infusion. In contrast to the regulations for Food Contact Materials (MCDA), there is currently no acceptable migration limits for the use of these plasticizers in clinical situations. In order to assess their migration, and thus control the risks linked to these MDs, we developed a migration model for the plasticizers in MDs. To this end, we applied a cross-disciplinary methodological process similar to that used in the food-processing industry, taking into account the MDs' conditions of use in clinical practice. The simulation model is simple and includes the following conditions: MD should be tested with a dynamic method that respects our established clinical assumption (2 L of infused solutions via 13 dm(2) of plasticized PVC), at a temperature of 25 degrees C and during 24 h of contact, using a 50/50 (v/v) ethanol/water simulant. This model could be proposed as a tool for the safety evaluation of the patients' exposure risk to plasticizers from PVC medical devices for infusions. PMID- 26278489 TI - Delivery and therapeutic applications of gene editing technologies ZFNs, TALENs, and CRISPR/Cas9. AB - In recent years, several new genome editing technologies have been developed. Of these the zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the CRISPR/Cas9 RNA-guided endonuclease system are the most widely described. Each of these technologies utilizes restriction enzymes to introduce a DNA double stranded break at a targeted location with the guide of homologous binding proteins or RNA. Such targeting is viewed as a significant advancement compared to current gene therapy methods that lack such specificity. Proof-of-concept studies have been performed to treat multiple disorders, including in vivo experiments in mammals and even early phase human trials. Careful consideration and investigation of delivery strategies will be required so that the therapeutic potential for gene editing is achieved. In this review, the mechanisms of each of these gene editing technologies and evidence of therapeutic potential will be briefly described and a comprehensive list of past studies will be provided. The pharmaceutical approaches of each of these technologies are discussed along with the current delivery obstacles. The topics and information reviewed herein provide an outline of the groundbreaking research that is being performed, but also highlights the potential for progress yet to be made using these gene editing technologies. PMID- 26278490 TI - Promoting brain remodeling to aid in stroke recovery. AB - Endogenous brain repair after stroke involves a set of highly interactive processes, such as angiogenesis, neurogenesis, oligodendrogenesis, synaptogenesis, and axonal outgrowth, which together orchestrate neurological recovery. During the past several years, there have been advances in our understanding of miRNAs and histone deacetylases (HDACs) in brain repair processes after stroke. Emerging data indicate the important role of exosomes for intercellular communication in promoting coupled brain remodeling processes. These advances will likely have a major impact on the development of restorative therapies for ischemic brain repair, consequently leading to improvement of neurological function. In this review, we provide an update on our current understanding of cellular and molecular mechanisms of miRNAs, exosomes, and HDACs in brain restorative processes after stroke. PMID- 26278491 TI - [(14)C]Fluciclovine (alias anti-[(14)C]FACBC) uptake and ASCT2 expression in castration-resistant prostate cancer cells. AB - INTRODUCTION: trans-1-Amino-3-[(18)F]fluorocyclobutanecarboxylic acid ([(18)F]fluciclovine, also known as anti-[(18)F]FACBC), is a tracer for positron emission tomography (PET) imaging for detection of tumors such as prostate cancer (PCa). Our previous study showed that ASCT2 (Na(+)-dependent amino acid transporter (AAT)) mediates fluciclovine uptake in androgen-dependent PCa cells; its expression is influenced by androgen, a key hormone in the progression of primary PCa and castration-resistant prostate cancer (CRPC). In this study, we investigated the uptake mechanisms and feasibility of [(18)F]fluciclovine for CRPC in the androgen-dependent PCa cell line LNCaP and LNCaP-derivatives LNCaP-SF and LN-REC4. METHODS: LNCaP-SF was established after long-term cultivation of LNCaP in steroid-free conditions, and LN-Pre and LN-REC4 were established from LNCaP inoculated in intact and castrated severe combined immunodeficient mice, respectively. Uptake and competitive inhibition experiments were performed with trans-1-amino-3-fluoro[1-(14)C]cyclobutanecarboxylic acid ([(14)C]fluciclovine) to characterize the involvement of AATs in androgen-dependent PCa (LNCaP and LN Pre) and CRPC-like (LNCaP-SF and LN-REC4) cell lines. AAT expression was analyzed by Western blotting, and [(14)C]fluciclovine uptake in androgen-dependent PCa and CRPC-like cell lines were investigated in the presence or absence of dihydrotestosterone (DHT). RESULTS: The contribution of Na(+)-dependent AATs to [(14)C]fluciclovine uptake in all cell lines was 88-98%, and [(14)C]fluciclovine uptake was strongly inhibited by L-glutamine and L-serine, the substrates for Na(+)-dependent alanine-serine-cysteine (system ASC) AATs, in the presence of Na(+). DHT enhanced ASCT2 expression in LNCaP, LN-Pre, and LN-REC4, but not in LNCaP-SF, and the responses of ASCT2 expression to DHT correlated with [(14)C]fluciclovine uptake. CONCLUSIONS: System ASC, especially ASCT2, could play a major role in [(14)C]fluciclovine uptake into CRPC-like and androgen-dependent PCa cells, suggesting [(18)F]fluciclovine-PET is applicable to the detection of CRPC as well as androgen-dependent PCa. ADVANCE IN KNOWLEDGE: [(18)F]fluciclovine PET may be applied for the detection of CRPC. IMPLICATION FOR PATIENT CARE: [(18)F]fluciclovine-PET may permit early intervention for CRPC treatment. PMID- 26278493 TI - Ten-Year Employment Patterns of Working Age Individuals After Moderate to Severe Traumatic Brain Injury: A National Institute on Disability and Rehabilitation Research Traumatic Brain Injury Model Systems Study. AB - OBJECTIVE: To describe the 10-year patterns of employment for individuals of working age discharged from a Traumatic Brain Injury Model Systems (TBIMS) center between 1989 and 2009. DESIGN: Secondary data analysis. SETTING: Inpatient rehabilitation centers. PARTICIPANTS: Patients aged 16 to 55 years (N=3618) who were not retired at injury, received inpatient rehabilitation at a TBIMS center, were discharged alive between 1989 and 2009, and had at least 3 completed follow up interviews at postinjury years 1, 2, 5, and 10. INTERVENTIONS: Not applicable. MAIN OUTCOMES MEASURE: Employment. RESULTS: Patterns of employment were generated using a generalized linear mixed model, where these patterns were transformed into temporal trajectories of probability of employment via random effects modeling. Covariates demonstrating significant relations to growth parameters that govern the trajectory patterns were similar to those noted in previous cross sectional research and included age, sex, race/ethnicity, education, preinjury substance misuse, preinjury vocational status, and days of posttraumatic amnesia. The calendar year in which the injury occurred also greatly influenced trajectories. An interactive tool was developed to provide visualization of all postemployment trajectories, with many showing decreasing probabilities of employment between 5 and 10 years postinjury. CONCLUSIONS: These results highlight that postinjury employment after moderate to severe traumatic brain injury (TBI) is a dynamic process, with varied patterns of employment for individuals with specific characteristics. The overall decline in trajectories of probability of employment between 5 and 10 years postinjury suggests that moderate to severe TBI may have unfavorable chronic effects and that employment outcome is highly influenced by national labor market forces. Additional research targeting the underlying drivers of the decline between 5 and 10 years postinjury is recommended, as are interventions that target influencing factors. PMID- 26278492 TI - Skin tissue repair: Matrix microenvironmental influences. AB - The process of repair of wounded skin involves intricate orchestration not only between the epidermal and dermal compartments but also between the resident and immigrant cells and the local microenvironment. Only now are we beginning to appreciate the complex roles played by the matrix in directing the outcome of the repair processes, and how this impacts the signals from the various cells. Recent findings speak of dynamic and reciprocal interactions that occurs among the matrix, growth factors, and cells that underlies this integrated process. Further confounding this integration are the physiologic and pathologic situations that directly alter the matrix to impart at least part of the dysrepair that occurs. These topics will be discussed with a call for innovative model systems of direct relevance to the human situation. PMID- 26278494 TI - Age-related changes in the endocannabinoid system in the mouse hippocampus. AB - Previous studies have demonstrated that the endocannabinoid system significantly influences the progression of brain ageing, and the hippocampus is one of the brain regions most vulnerable to ageing and neurodegeneration. We have further examined age-related changes in the hippocampal endocannabinoid system by measuring the levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in young and old mice from two different mouse strains. We found a decrease in 2-AG but not AEA levels in aged mice. In order to identify the cause for 2-AG level changes, we investigated the levels of several enzymes that contribute to synthesis and degradation of 2-AG in the hippocampus. We found a selective decrease in DAGLalpha mRNA and protein levels as well as an elevated MAGL activity during ageing. We hypothesize that the observed decrease of 2-AG levels is probably caused by changes in DAGLalpha expression and MAGL activity. This finding can contribute to the existing knowledge about the processes underlying selective vulnerability of the hippocampus to ageing and age-related neurodegeneration. PMID- 26278495 TI - An estimation of the clinical mastitis incidence per 100 cows per year based on routinely collected herd data. AB - The aim of this study was to evaluate whether it was possible to (1) estimate the clinical mastitis incidence rate (CMI) for all Dutch dairy herds and (2) to detect farms with a high CMI based on routinely collected herd data. For this study, 240 dairy farms with a conventional milking system that participated in the milk recording program every 4 to 6 wk were randomly selected and agreed to participate. From the initial 240 herds, data of clinical mastitis (CM) registrations and routinely collected herd data of 227 herds were complete and could be used for analysis. Routinely collected herd data consisted of identification and registration records, antimicrobial usage, test-day records from the milk recording program, bulk tank milk (BTM) somatic cell count data and results of diagnostic tests on BTM samples. For each of the 227 herds, the CMI per 100 cows per year was calculated per quarter of the year and was combined with the available herd data. Two models were developed to predict the CMI for all dairy herds and to detect individual herds that belonged to the 25% herds with the highest CMI. Records of 156 (67%) herds were used for development of the models and the remaining 71 (33%) were used for validation. The model that estimated the CMI in all herds consisted of 11 explanatory variables. The observed and predicted averages of the validation herds were not significantly different. The model estimated a CMI per 100 cows per year of 32.5 cases (95% confidence interval=30.2-34.8), whereas the farmers registered 33.4 cases (95% confidence interval=29.5-37.4). The model that aimed at detecting individual herds with a high CMI contained 6 explanatory variables and could correctly classify 77% of all validation herds at the quarter-year level. The most important variables in the model were antibiotic usage for treating CM and BTM somatic cell count. In conclusion, models based on routinely collected herd data gave an accurate prediction of CMI for all Dutch dairy herds and could detect individual dairy herds with a high CMI. With these models it is possible to periodically monitor CMI both at the herd and at the national level, which is valuable for monitoring purposes and can motivate farmers to continuously improve udder health in their herds. PMID- 26278496 TI - The influence of age and weaning on permeability of the gastrointestinal tract in Holstein bull calves. AB - Fourteen Holstein bull calves were used in a randomized complete block design to investigate the effect of calf age and weaning on permeability of the gastrointestinal tract (GIT). Calves were randomly assigned to 1 of 2 treatments: (1) a weaning protocol that was initiated on d 35; WN; n=7), or (2) a control treatment where calves were not weaned (CON; n=7). Calves were bottle-fed milk replacer (150 g/L), in 3 equal portions/d targeting 15% of their body weight (BW) in liquid milk intake [approximately 21.1g/kg of BW/d, dry matter (DM) basis]. On d 35, the amount of milk replacer offered to WN calves was reduced to 7.5% of BW for 7 d before calves were weaned on d 42. On d 14, 28, and 42, calves were orally dosed with 500 mL of Cr-EDTA (179 mM Cr-EDTA solution) and housed in a metabolism crate to enable total urine collection and determination of total urinary Cr recovery as an indicator of total-tract permeability. On d 44, calves were killed and tissues from the rumen, omasum, duodenum, jejunum, ileum, cecum, and proximal and distal colon were collected, rinsed, and transported in buffer solution (pH 7.4 at 38.5 degrees C). Tissues were incubated in Ussing chambers under short-circuit conditions with buffer solutions designed to mimic the mucosal and serosal energy source that would be available in vivo (glucose for tissues from the small intestine and short-chain fatty acids for tissues that would be exposed to fermentation; rumen, omasum, and large intestinal tissues). The serosal to mucosal flux of (14)C-mannitol and (3)H-inulin was measured for each region. Although we detected treatment * period interactions for BW and starter intake, dietary treatments did not differ within a week. Overall, the time that ruminal pH was <5.5 was less before weaning than after weaning. We observed a differential response for the appearance of Cr in urine for WN and CON calves, where the appearance of Cr (mg/48 h) in urine decreased for both treatments from d 14 to 28, but increased from d 28 to 42 for WN, whereas Cr appearance continued to decrease for CON. The flux of mannitol and inulin did not differ between treatments but did differ among region of the GIT, with rumen, duodenum, and jejunum having the greatest permeability. These data suggest that permeability of the GIT decreases with age but weaning may disrupt this process. The rumen, duodenum, and jejunum appear to be the regions with greatest permeability. PMID- 26278497 TI - A child with myoclonus-dystonia (DYT11) misdiagnosed as atypical opsoclonus myoclonus syndrome. AB - INTRODUCTION: DYT11 is an autosomal dominant inherited movement disorder characterized by myoclonus and dystonia. CLINICAL PRESENTATION: We present a case with atypical symptoms and with episodes of ataxia and myoclonus preceded by infections. Atypical presentation of opsoclonus myoclonus syndrome was suspected and treatment with bolus steroids and immunoglobulin were initiated with some response over 28 months. A re-evaluation gave suspicion of a dyskinetic disorder and whole exome-sequencing was performed but no causal variant was identified. OUTCOME: A specific analysis of the SGCE gene was subsequently initiated, which revealed a pathogenic aberration confirming the diagnosis of DYT11. CONCLUSION: A clinical DYT11 diagnosis can be difficult to establish in early childhood without a known family history. PMID- 26278498 TI - A de-novo interstitial microduplication involving 2p16.1-p15 and mirroring 2p16.1 p15 microdeletion syndrome: Clinical and molecular analysis. AB - BACKGROUND: Microdeletions of various sizes in the 2p16.1-p15 chromosomal region have been grouped together under the 2p16.1-p15 microdeletion syndrome. Children with this syndrome generally share certain features including microcephaly, developmental delay, facial dysmorphism, urogenital and skeletal abnormalities. We present a child with a de-novo interstitial 1665 kb duplication of 2p16.1-p15. METHODS AND RESULTS: Clinical features of this child are distinct from those of children with the 2p16.1-p15 microdeletion syndrome, specifically the head circumference which is within the normal range and mild intellectual disability with absence of autistic behaviors. Microduplications many times bear milder clinical phenotypes in comparison with corresponding microdeletion syndromes. Indeed, as compared to the microdeletion syndrome patients, the 2p16.1-p15 microduplication seems to have a milder cognitive effect and no effect on other body systems. Limited information available in genetic databases about cases with overlapping duplications indicates that they all have abnormal developmental phenotypes. CONCLUSION: The involvement of genes in this location including BCL11A, USP34 and PEX13, affecting fundamental developmental processes both within and outside the nervous system may explain the clinical features of the individual described in this report. PMID- 26278499 TI - Strategies to improve the quality of survival for childhood brain tumour survivors. AB - BACKGROUND: Tumours of the central nervous system (CNS) are the most frequent solid tumours and the second most frequent type of cancer in children and adolescents. Overall survival has continuously improved in Germany, since an increasing number of patients have been treated according to standardised, multicentre, multimodal treatment recommendations, trials of the German Paediatric Brain Tumour Consortium (HIT-Network) or the International Society of Paediatric Oncology-Europe (SIOP-E) during the last decades. Today, two out of three patients survive. At least 8000 long-term childhood brain tumour survivors (CBTS) are currently living in Germany. They face lifelong disease- and treatment related late effects (LE) and associated socioeconomic problems more than many other childhood cancer survivors (CCS). METHOD: We review the LE and resulting special needs of this particular group of CCS. RESULTS: Despite their increasing relevance for future treatment optimisation, neither the diversity of chronic and cumulative LE nor their pertinent risk factors and subsequent impact on quality of survival have yet been comprehensively addressed for CBTS treated according to HIT- or SIOP-E-protocols. Evidence-based information to empower survivors and stakeholders, as well as medical expertise to manage their individual health care, psychosocial and educational/vocational needs must still be generated and established. CONCLUSION: The establishment of a long-term research- and care network in Germany shall contribute to a European platform, that aims at optimising CBTSs' transition into adulthood as resilient individuals with high quality of survival including optimal levels of activity, participation and acceptance by society. PMID- 26278500 TI - The effect of albumin and cholesterol on the biotribological behavior of hydrogels for contact lenses. AB - The irritation/discomfort associated with the use of contact lenses (CLs) is often related to the eyelid-lens friction. Although the use of such devices is widespread, the information about the influence of the lacrimal fluid biomolecules on the tribological behavior of the CLs hydrogels is scarce. In this work, we investigated the effect of the presence of albumin and cholesterol in the lubricant medium, on the frictional response of two model hydrogels for CLs: a hydroxyethylmethacrylate based hydrogel, HEMA/PVP, and a silicone based one, TRIS/NVP/HEMA. Tribological experiments were done in a nanotribometer, in water and in the presence of solutions of those biomolecules. It was observed a significant increase of the friction coefficient (MU) for HEMA/PVP when the lubricant contains cholesterol, and for TRIS/NVP/HEMA when it contains albumin. Solid-state NMR and DSC analysis revealed that HEMA/PVP hydrated in cholesterol solution has a lower amount of free and loosely bound water than the hydrogel hydrated in water. Therefore, a smaller amount of water shall be released into the contact region during the friction tests with cholesterol solution, leading to a thinner film in the contact zone, and consequently to a higher MU. Concerning TRIS/NVP/HEMA, QCM-D studies showed that this hydrogel adsorbs less albumin than HEMA/PVP and that the formed film is more rigid, which can explain the increase of MU. The obtained results contribute to understand the influence of lacrimal fluid composition on the tribological behavior of CLs materials, being relevant for the selection and optimization of these devices. STATEMENT OF SIGNIFICANCE: Understanding the tribological behavior of contact lenses (CLs) materials in contact with the lacrimal fluid and the role of its components is of major importance to optimize the comfort and overall success of these devices. Nevertheless, the available information on this subject in the literature is scarce. In this work, the effect of albumin and cholesterol (two of the main components of the lacrimal fluid) on the frictional response of distinct types of hydrogels suitable for CLs, is compared, for the first time. Significant differences were observed with the two molecules, depending on the material, stressing the need to further study this issue to understand, predict and optimize the in vivo performance of CLs. PMID- 26278501 TI - The Functional Lumen Imaging Probe Detects Esophageal Contractility Not Observed With Manometry in Patients With Achalasia. AB - BACKGROUND & AIMS: The functional lumen imaging probe (FLIP) could improve the characterization of achalasia subtypes by detecting nonocclusive esophageal contractions not observed with standard manometry. We aimed to evaluate esophageal contractions during volumetric distention in patients with achalasia using FLIP topography. METHODS: Fifty-one treatment-naive patients with achalasia, defined and subclassified by high-resolution esophageal pressure topography, and 10 asymptomatic individuals (controls) were evaluated with the FLIP during endoscopy. During stepwise distension, simultaneous intrabag pressures and 16 channels of cross-sectional areas were measured; data were exported to software that generated FLIP topography plots. Esophageal contractility was identified by noting periods of reduced luminal diameter. Esophageal contractions were characterized further by propagation direction, repetitiveness, and based on whether they were occluding or nonoccluding. RESULTS: Esophageal contractility was detected in all 10 controls: 8 of 10 had repetitive antegrade contractions and 9 of 10 had occluding contractions. Contractility was detected in 27% (4 of 15) of patients with type I achalasia and in 65% (18 of 26, including 9 with occluding contractions) of patients with type II achalasia. Contractility was detected in all 10 patients with type III achalasia; 8 of these patients had a pattern of contractility that was not observed in controls (repetitive retrograde contractions). CONCLUSIONS: Esophageal contractility not observed with manometry can be detected in patients with achalasia using FLIP topography. The presence and patterns of contractility detected with FLIP topography may represent variations in pathophysiology, such as mechanisms of panesophageal pressurization in patients with type II achalasia. These findings could have implications for additional subclassification to supplement prediction of the achalasia disease course. PMID- 26278502 TI - Liver Stem Cells: Experimental Findings and Implications for Human Liver Disease. AB - Evidence from human histopathology and experimental studies with rodents and zebrafish has shown that hepatocytes and cholangiocytes may function as facultative stem cells for each other in conditions of impaired regeneration. The interpretation of the findings derived from these studies has generated considerable discussion and some controversies. This review examines the evidence obtained from the different experimental models and considers implications that these studies may have for human liver disease. PMID- 26278504 TI - American Gastroenterological Association Institute Technical Review on the Role of Upper Gastrointestinal Biopsy to Evaluate Dyspepsia in the Adult Patient in the Absence of Visible Mucosal Lesions. PMID- 26278505 TI - BioCapacitor: A novel principle for biosensors. AB - Studies regarding biofuel cells utilizing biocatalysts such as enzymes and microorganisms as electrocatalysts have been vigorously conducted over the last two decades. Because of their environmental safety and sustainability, biofuel cells are expected to be used as clean power generators. Among several principles of biofuel cells, enzyme fuel cells have attracted significant attention for their use as alternative energy sources for future implantable devices, such as implantable insulin pumps and glucose sensors in artificial pancreas and pacemakers. However, the inherent issue of the biofuel cell principle is the low power of a single biofuel cell. The theoretical voltage of biofuel cells is limited by the redox potential of cofactors and/or mediators employed in the anode and cathode, which are inadequate for operating any devices used for biomedical application. These limitations inspired us to develop a novel biodevice based on an enzyme fuel cell that generates sufficient stable power to operate electric devices, designated "BioCapacitor." To increase voltage, the enzyme fuel cell is connected to a charge pump. To obtain a sufficient power and voltage to operate an electric device, a capacitor is used to store the potential generated by the charge pump. Using the combination of a charge pump and capacitor with an enzyme fuel cell, high voltages with sufficient temporary currents to operate an electric device were generated without changing the design and construction of the enzyme fuel cell. In this review, the BioCapacitor principle is described. The three different representative categories of biodevices employing the BioCapacitor principle are introduced. Further, the recent challenges in the developments of self-powered stand-alone biodevices employing enzyme fuel cells combined with charge pumps and capacitors are introduced. Finally, the future prospects of biodevices employing the BioCapacitor principle are addressed. PMID- 26278503 TI - Characterization of genetic loci that affect susceptibility to inflammatory bowel diseases in African Americans. AB - BACKGROUND & AIMS: Inflammatory bowel disease (IBD) has familial aggregation in African Americans (AAs), but little is known about the molecular genetic susceptibility. Mapping studies using the Immunochip genotyping array expand the number of susceptibility loci for IBD in Caucasians to 163, but the contribution of the 163 loci and European admixture to IBD risk in AAs is unclear. We performed a genetic mapping study using the Immunochip to determine whether IBD susceptibility loci in Caucasians also affect risk in AAs and identify new associated loci. METHODS: We recruited AAs with IBD and without IBD (controls) from 34 IBD centers in the United States; additional controls were collected from 4 other Immunochip studies. Association and admixture loci were mapped for 1088 patients with Crohn's disease, 361 with ulcerative colitis, 62 with IBD type unknown, and 1797 controls; 130,241 autosomal single-nucleotide polymorphisms (SNPs) were analyzed. RESULTS: The strongest associations were observed between ulcerative colitis and HLA rs9271366 (P = 7.5 * 10(-6)), Crohn's disease and 5p13.1 rs4286721 (P = 3.5 * 10(-6)), and IBD and KAT2A rs730086 (P = 2.3 * 10( 6)). Additional suggestive associations (P < 4.2 * 10(-5)) were observed between Crohn's disease and IBD and African-specific SNPs in STAT5A and STAT3; between IBD and SNPs in IL23R, IL12B, and C2orf43; and between ulcerative colitis and SNPs near HDAC11 and near LINC00994. The latter 3 loci have not been previously associated with IBD, but require replication. Established Caucasian associations were replicated in AAs (P < 3.1 * 10(-4)) at NOD2, IL23R, 5p15.3, and IKZF3. Significant admixture (P < 3.9 * 10(-4)) was observed for 17q12-17q21.31 (IZKF3 through STAT3), 10q11.23-10q21.2, 15q22.2-15q23, and 16p12.2-16p12.1. Network analyses showed significant enrichment (false discovery rate <1 * 10(-5)) in genes that encode members of the JAK-STAT, cytokine, and chemokine signaling pathways, as well those involved in pathogenesis of measles. CONCLUSIONS: In a genetic analysis of 3308 AA IBD cases and controls, we found that many variants associated with IBD in Caucasians also showed association evidence with these diseases in AAs; we also found evidence for variants and loci not previously associated with IBD. The complex genetic factors that determine risk for or protection against IBD in different populations require further study. PMID- 26278506 TI - Metabolic engineering of cyanobacteria for photosynthetic 3-hydroxypropionic acid production from CO2 using Synechococcus elongatus PCC 7942. AB - Photosynthetic conversion of CO2 to chemicals using cyanobacteria is an attractive approach for direct recycling of CO2 to useful products. 3 Hydroxypropionic acid (3 HP) is a valuable chemical for the synthesis of polymers and serves as a precursor to many other chemicals such as acrylic acid. 3 HP is naturally produced through glycerol metabolism. However, cyanobacteria do not possess pathways for synthesizing glycerol and converting glycerol to 3 HP. Furthermore, the latter pathway requires coenzyme B12, or an oxygen sensitive, coenzyme B12-independent enzyme. These characteristics present major challenges for production of 3 HP using cyanobacteria. To overcome such difficulties, we constructed two alternative pathways in Synechococcus elongatus PCC 7942: a malonyl-CoA dependent pathway and a beta-alanine dependent pathway. Expression of the malonyl-CoA dependent pathway genes (malonyl-CoA reductase and malonate semialdehyde reductase) enabled S. elongatus to synthesize 3 HP to a final titer of 665 mg/L. beta-Alanine dependent pathway expressing S. elongatus produced 3H P to final titer of 186 mg/L. These results demonstrated the feasibility of converting CO2 into 3 HP using cyanobacteria. PMID- 26278507 TI - [Radiosurgery for 1-4 brain metastases: Radiosurgery alone may be the preferred treatment]. PMID- 26278508 TI - Metabolism of the Fusarium Mycotoxins T-2 Toxin and HT-2 Toxin in Wheat. AB - To investigate the metabolic fate of HT-2 toxin (HT2) and T-2 toxin (T2) in wheat (Triticum aestivum L.), an untargeted metabolomics study utilizing stable isotopic labeling and liquid chromatography-high resolution mass spectrometry was performed. In total, 11 HT2 and 12 T2 derived in planta biotransformation products were annotated putatively. In addition to previously reported mono- and diglucosylated forms of HT2, evidence for the formation of HT2-malonyl-glucoside and feruloyl-T2, as well as acetylation and deacetylation products in wheat was obtained for the first time. To monitor the kinetics of metabolite formation, a time course experiment was conducted involving the Fusarium head blight susceptible variety Remus and the resistant cultivar CM-82036. Biotransformation reactions were observed already at the earliest tested time point (6 h after treatment), and formed metabolites showed different kinetic profiles. After ripening, less than 15% of the toxins added to the plants were determined to be unmetabolized. PMID- 26278509 TI - Hydrogen production at high Faradaic efficiency by a bio-electrode based on TiO2 adsorption of a new [FeFe]-hydrogenase from Clostridium perfringens. AB - The [FeFe]-hydrogenase CpHydA from Clostridium perfringens was immobilized by adsorption on anatase TiO2 electrodes for clean hydrogen production. The immobilized enzyme proved to perform direct electron transfer to and from the electrode surface and catalyses both H2 oxidation (H2 uptake) and H2 production (H2 evolution) with a current density for H2 evolution of about 2 mA cm(-1). The TiO2/CpHydA bioelectrode remained active for several days upon storage and when a reducing potential was set, H2 evolution occurred with a mean Faradaic efficiency of 98%. The high turnover frequency of H2 production and the tight coupling of electron transfer, resulting in a Faradaic efficiency close to 100%, support the exploitation of the novel TiO2/CpHydA stationary electrode as a powerful device for H2 production. PMID- 26278510 TI - The influence of latent toxoplasmosis on women's reproductive function: four cross-sectional studies. AB - Several studies have investigated the association between infection with Toxoplasma gondii (Nicolle et Manceaux, 1908), pregnancy and fertility, but the results of studies focused on the fertility are rather ambiguous. Here we report results of four new cross-sectional studies. The studies were performed in the General University Hospital, Prague (study A with n = 1 165, and study C with n = 317), in private clinics of the Centre of Reproductive Medicine, Prague (study B with n = 1 016), and in a population of Czech and Slovak volunteers from the Facebook page 'Guinea Pigs' willing to participate in various basic science studies (study D with n = 524). In studies A and B, the clinical records were used to assess the fertility problems, whereas in studies C and D, the women were asked to rate their fertility problems using a six-point scale. Pregnant T. gondii-infected women were older than T. gondii-free women (study A: 33.1 vs 31.2, P < 0.001; study B: 30.6 vs 29.6, P = 0.012) and more often used assisted reproductive technology to conceive (study A: 17.2% vs 12.4%, P = 0.041; study B: 13.4% vs 9.2%, P = 0.317). Pregnant T. gondii-infected primiparous women were older than T. gondii-free primiparas (study A: 31.1 vs 29.5, P < 0.001; study B: 29.7 vs 28.9, P = 0.064) and more often used assisted reproductive technology to conceive (study A: 24.7% vs 14.4%, P = 0.010; study B: 15.9% vs 15.5%, P = 0.888). T. gondii-infected women reported to take a longer time to conceive than T. gondii-free women (P = 0.015). They also claimed to have more fertility problems than T. gondii-free women (P < 0.0001). Our results suggest that 'asymptomatic' latent toxoplasmosis could be a more serious source of fertility problems and health-associated burden than more severe but far rarer congenital toxoplasmosis. PMID- 26278512 TI - Enhanced antitumour drug delivery to cholangiocarcinoma through the apical sodium dependent bile acid transporter (ASBT). AB - Novel antitumour drugs, such as cationic tyrosine kinase inhibitors, are useful in many types of cancer but not in others, such as cholangiocarcinoma (CCA), where their uptake through specific membrane transporters, such as OCT1, is very poor. Here we have investigated the usefulness of targeting cytostatic bile acid derivatives to enhance the delivery of chemotherapy to tumours expressing the bile acid transporter ASBT and whether this is the case for CCA. The analysis of paired samples of CCA and adjacent non-tumour tissue collected from human (n=15) and rat (n=29) CCA revealed that ASBT expression was preserved. Moreover, ASBT was expressed, although at different levels, in human and rat CCA cell lines. Both cells in vitro and rat tumours in vivo were able to carry out efficient uptake of bile acid derivatives. Using Bamet-UD2 (cisplatin-ursodeoxycholate conjugate) as a model ASBT-targeted drug, in vitro and in vivo antiproliferative activity was evaluated. ASBT expression enhanced the sensitivity to Bamet-UD2, but not to cisplatin, in vitro. In nude mice, Bamet-UD2 (more than cisplatin) inhibited the growth of human colon adenocarcinoma tumours with induced stable expression of ASBT. As compared with cisplatin, administration of Bamet-UD2 to rats with CCA resulted in an efficient liver and tumour uptake but low exposure of extrahepatic tissues to the drug. Consequently, signs of liver/renal toxicity were absent in animals treated with Bamet-UD2. In conclusion, endogenous or induced ASBT expression may be useful in pharmacological strategies to treat enterohepatic tumours based on the use of cytostatic bile acid derivatives. PMID- 26278514 TI - Probing structural patterns of ion association and solvation in mixtures of imidazolium ionic liquids with acetonitrile by means of relative (1)H and (13)C NMR chemical shifts. AB - Mixtures of ionic liquids (ILs) with polar aprotic solvents in different combinations and under different conditions (concentration, temperature etc.) are used widely in electrochemistry. However, little is known about the key intermolecular interactions in such mixtures depending on the nature of the constituents and mixture composition. In order to systematically address the intermolecular interactions, the chemical shift variation of (1)H and (13)C nuclei has been followed in mixtures of imidazolium ILs 1-n-butyl-3 methylimidazolium tetrafluoroborate (BmimBF4), 1-n-butyl-3-methylimidazolium hexafluorophosphate (BmimPF6), 1-n-butyl-3-methylimidazolium trifluoromethanesulfonate (BmimTfO) and 1-n-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (BmimTFSI) with molecular solvent acetonitrile (AN) over the entire composition range at 300 K. The concept of relative chemical shift variation is proposed to assess the observed effects on a unified and unbiased scale. We have found that hydrogen bonds between the imidazolium ring hydrogen atoms and electronegative atoms of anions are stronger in BmimBF4 and BmimTfO ILs than those in BmimTFSI and BmimPF6. Hydrogen atom at position 2 of the imidazolium ring is substantially more sensitive to interionic hydrogen bonding than those at positions 4-5 in the case of BmimTfO and BmimTFSI ILs. These hydrogen bonds are disrupted upon dilution in AN due to ion dissociation which is more pronounced at high dilutions. Specific solvation interactions between AN molecules and IL cations are poorly manifested. PMID- 26278513 TI - Patient and Physician Perspectives on Mode of Administration of the PCSK9 Monoclonal Antibody Alirocumab, an Injectable Medication to Lower LDL-C Levels. AB - PURPOSE: Clinical trials of the PCSK9 inhibitor alirocumab, an every 2 week injectable monoclonal antibody, have shown significant reductions in LDL cholesterol. However, many patients requiring lipid-lowering therapy are not experienced with self-injected medication. This study assessed patient and physician perceptions of 2 alirocumab delivery devices. METHODS: 400 participants (200 physicians, 200 patients) were included from 6 countries. Physicians (99 primary care physicians [PCPs]; 101 specialists) had mean practice experience of 17.8 years and an average of 797 hypercholesterolemic patients. Participating patients had LDL-C levels above their goal and at least one of the following: familial hypercholesterolemia, statin intolerance, high cardiovascular risk, and/or diabetes. Mean patient age was 58.5 years, 51% were female, and 25.5% had injectable medication experience. Following device instruction and demonstration, participants tested either a pre-filled pen or pre-filled syringe, using both 75 and 150 mg doses of single-blinded placebo into a prosthetic pad. Data were collected by self-administered questionnaire. FINDINGS: Participant acceptance of both devices was positive, with 83-100% agreeing with ease-of-use statements. After testing, physicians estimated that 66% (pen) and 58% (syringe) of their patients would be willing to self-inject using the device (relative increases from pre-testing of 22% and 16%, respectively; both P<0.05). Specialist estimates were higher than PCP estimates: for the pen, 60% versus 47% (pre-testing), respectively, and 72% versus 61% (post-testing); for the syringe, 57% versus 43% (pre-testing), 63% versus 54% (post-testing; all P<0.05, specialist vs PCP). After testing, 72% (pen) and 63% (syringe) of patient-participants were very willing to self-inject (relative increases from pre-testing of 26% [P<0.05] and 11%, respectively); 96% (pen) and 93% (syringe) were either very willing or somewhat willing to self-inject. The proportion of patients aged <60 years who were very willing to self-inject with either device was numerically (but not statistically) higher compared with those >=60 years. Initially, patients with injectable medication experience were generally more willing to use the pen than injection-naive patients; after testing there was no difference between groups. No significant differences were observed in responses to the 2 different doses. IMPLICATIONS: Responses from physicians and patients to pre-filled pen and syringe devices were positive. Devices were considered easy to operate, with most patients willing to use and accept self-injection. Patient willingness to self inject increased after demonstration and testing. Results suggest that, in clinical practice, alirocumab administration by either pre-filled pen or syringe would not deter most physicians from prescribing or most patients from self administering. PMID- 26278515 TI - Reactive interlayer based ultra-low moisture permeable membranes for organic photovoltaic encapsulation. AB - Reactive interlayers consisting of zero valent iron and copper nanoparticles have been successfully incorporated into Surlyn films to fabricate moisture barrier materials with reduced water vapor permeabilities. The reactive nanoparticles dispersed in stearic acid were employed as the interlayers due to their ability to react with moisture. The water vapor transmission rates through the fabricated barrier films with reactive iron and copper interlayers decreased by over 4 orders of magnitude when compared to neat Surlyn. The flexibility and transparency of the barrier films have been evaluated by tensile and UV-visible experiments. Moreover, the accelerated aging studies conducted in accordance with the ISOS-III protocol confirmed the increased lifetimes of the organic photovoltaic (OPV) devices encapsulated with these reactive barrier films. PMID- 26278516 TI - Fueling the Brain--a New Role in Lactate Metabolism. PMID- 26278511 TI - Drug transporters in tissues and cells relevant to sexual transmission of HIV: Implications for drug delivery. AB - Efflux and uptake transporters of drugs are key regulators of the pharmacokinetics of many antiretroviral drugs. A growing body of literature has revealed the expression and functionality of multiple transporters in female genital tract (FGT), colorectal tissue, and immune cells. Drug transporters could play a significant role in the efficacy of preventative strategies for HIV-1 acquisition. Pre-exposure prophylaxis (PrEP) is a promising strategy, which utilizes topically (vaginally or rectally), orally or other systemically administered antiretroviral drugs to prevent the sexual transmission of HIV to receptive partners. The drug concentration in the receptive mucosal tissues and target immune cells for HIV is critical for PrEP effectiveness. Hence, there is an emerging interest in utilizing transporter information to explain tissue disposition patterns of PrEP drugs, to interpret inter-individual variability in PrEP drug pharmacokinetics and effectiveness, and to improve tissue drug exposure through modulation of the cervicovaginal, colorectal, or immune cell transporters. In this review, the existing literature on transporter expression, functionality and regulation in the transmission-related tissues and cells is summarized. In addition, the relevance of transporter function for drug delivery and strategies that could exploit transporters for increased drug concentration at target locales is discussed. The overall goal is to facilitate an understanding of drug transporters for PrEP optimization. PMID- 26278517 TI - Mild partial deoxygenation of esters catalyzed by an oxazolinylborate-coordinated rhodium silylene. AB - An electrophilic, coordinatively unsaturated rhodium complex supported by borate linked oxazoline, oxazoline-coordinated silylene, and N-heterocyclic carbene donors [{kappa(3)-N,Si,C-PhB(Ox(Me2))(Ox(Me2)SiHPh)Im(Mes)}Rh(H)CO][HB(C6F5)3] (, Ox(Me2) = 4,4-dimethyl-2-oxazoline; Im(Mes) = 1-mesitylimidazole) is synthesized from the neutral rhodium silyl {PhB(Ox(Me2))2Im(Mes)}RhH(SiH2Ph)CO () and B(C6F5)3. The unusual oxazoline-coordinated silylene structure in is proposed to form by rearrangement of an unobserved isomeric cationic rhodium silylene species [{PhB(Ox(Me2))2Im(Mes)}RhH(SiHPh)CO][HB(C6F5)3] generated by H abstraction. Complex catalyzes reductions of organic carbonyl compounds with silanes to give hydrosilylation products or deoxygenation products. The pathway to these reactions is primarily influenced by the degree of substitution of the organosilane. Reactions with primary silanes give deoxygenation of esters to ethers, amides to amines, and ketones and aldehydes to hydrocarbons, whereas tertiary silanes react to give 1,2-hydrosilylation of the carbonyl functionality. In contrast, the strong Lewis acid B(C6F5)3 catalyzes the complete deoxygenation of carbonyl compounds to hydrocarbons with PhSiH3 as the reducing agent. PMID- 26278519 TI - Comparison of Cytologic Characteristics between Adenoid Cystic Carcinoma and Adenoid Basal Carcinoma in the Uterine Cervix. AB - BACKGROUND: Adenoid cystic carcinoma (ACC) and adenoid basal carcinoma (ABC) are rare in the uterine cervix. ACC is more aggressive than ABC, thus accurate differential diagnosis is important. In this study, we identified cytologic features useful in distinguishing these two tumors for diagnosis. METHODS: Three cases of ACC and five cases of ABC were selected for this study. Cervicovaginal smear slides were reviewed retrospectively, and the area, circumference, major axis, and minor axis of nuclei were measured using an image analyzer. RESULTS: ACC displayed three-dimensional clusters with a small acini pattern. ABC displayed peripheral palisading without an acini pattern. The nuclei of ACC were more irregular and angulated than those of ABC, and the former showed a coarsely granular chromatin pattern. The nucleic area, circumference, major axis, and minor axis were 18.556+/-8.665 um(2), 23.320+/-11.412 um, 5.664+/-1.537 um, and 4.127+/-1.107 um in ACC and 11.017+/-4.440 um(2), 15.920+/-5.664 um, 4.612+/ 1.025 um, and 3.088+/-0.762 um in the cases of ABC. All measured values showed statistically significant difference (p < .001). CONCLUSIONS: Although the nuclei of both of these tumor types were oval shaped, inferred from the ratio of minor axis to major axis (0.728 in ACC and 0.669 in ABC), the area of nuclei was approximately 1.7 times larger in ACC than in ABC. Distinguishing nucleic features, including area, morphology, and chromatin pattern, may be helpful in making a correct diagnosis. PMID- 26278518 TI - Current Issues and Clinical Evidence in Tumor-Infiltrating Lymphocytes in Breast Cancer. AB - With the advance in personalized therapeutic strategies in patients with breast cancer, there is an increasing need for biomarker-guided therapy. Although the immunogenicity of breast cancer has not been strongly considered in research or practice, tumor-infiltrating lymphocytes (TILs) are emerging as biomarkers mediating tumor response to treatments. Earlier studies have provided evidence that the level of TILs has prognostic value and the potential for predictive value, particularly in triple-negative and human epidermal growth factor receptor 2-positive breast cancer. Moreover, the level of TILs has been associated with treatment outcome in patients undergoing neoadjuvant chemotherapy. To date, no standardized methodology for measuring TILs has been established. In this article, we review current issues and clinical evidence for the use of TILs in breast cancer. PMID- 26278520 TI - Clustering and phase behaviour of attractive active particles with hydrodynamics. AB - We simulate clustering, phase separation and hexatic ordering in a monolayered suspension of active squirming disks subject to an attractive Lennard-Jones-like pairwise interaction potential, taking hydrodynamic interactions between the particles fully into account. By comparing the hydrodynamic case with counterpart simulations for passive and active Brownian particles, we elucidate the relative roles of self-propulsion, interparticle attraction, and hydrodynamic interactions in determining clustering and phase behaviour. Even in the presence of an attractive potential, we find that hydrodynamic interactions strongly suppress the motility induced phase separation that might a priori have been expected in a highly active suspension. Instead, we find only a weak tendency for the particles to form stringlike clusters in this regime. At lower activities we demonstrate phase behaviour that is broadly equivalent to that of the counterpart passive system at low temperatures, characterized by regimes of gas-liquid, gas-solid and liquid-solid phase coexistence. In this way, we suggest that a dimensionless quantity representing the level of activity relative to the strength of attraction plays the role of something like an effective non-equilibrium temperature, counterpart to the (dimensionless) true thermodynamic temperature in the passive system. However there are also some important differences from the equilibrium case, most notably with regards the degree of hexatic ordering, which we discuss carefully. PMID- 26278522 TI - Psychosocial presentation of revisional LAGB patients: a qualitative study. AB - This qualitative study offers insight into the experiences, expectations, perceptions and beliefs that may lead to laparoscopic adjustable gastric band patients' failure to achieve expected weight loss and seek revisional bariatric surgery. The 23 participants from two sites were interviewed and data were analysed from a grounded theory methodology in order to build a causal model. Analysis of participants' reports identified 'unrealistic expectations of the LAGB' as the core category. Additionally, the restriction of the band had a negative impact on participants' social interactions, leading to feelings of deprivation and, thus, to a desire for reward from food choices and consequently an increase of consumption of high-calorie-dense foods. These foods were chosen because of their specific texture or ability to provide reward. The resulting increase in weight or failure to achieve excess weight loss, led to feelings of shame and loneliness and emotional eating resulting in increased the consumption of rewarding foods. Thus, identifying unrealistic expectations of laparoscopic adjustable gastric band (LAGB) and emotional eating behaviours are important in those who are present initially for primary bariatric and revisional bariatric surgery, as they may contribute specifically to these patients' weight regain and consequent failure to achieve excess weight loss. PMID- 26278521 TI - Logistic, ethical, and political dimensions of stepped wedge trials: critical review and case studies. AB - BACKGROUND: Three arguments are usually invoked in favour of stepped wedge cluster randomised controlled trials: the logistic convenience of implementing an intervention in phases, the ethical benefit of providing the intervention to all clusters, and the potential to enhance the social acceptability of cluster randomised controlled trials. Are these alleged benefits real? We explored the logistic, ethical, and political dimensions of stepped wedge trials using case studies of six recent evaluations. METHODS: We identified completed or ongoing stepped wedge evaluations using two systematic reviews. We then purposively selected six with a focus on public health in high, middle, and low-income settings. We interviewed their authors about the logistic, ethical, and social issues faced by their teams. Two authors reviewed interview transcripts, identified emerging issues through qualitative thematic analysis, reflected upon them in the context of the literature, and invited all participants to co-author the manuscript. RESULTS: Our analysis raises three main points. First, the phased implementation of interventions can alleviate problems linked to simultaneous roll-out, but also brings new challenges. Issues to consider include the feasibility of organising intervention activities according to a randomised sequence, estimating time lags in implementation and effects, and accommodating policy changes during the trial period. Second, stepped wedge trials, like parallel cluster trials, require equipoise: without it, randomising participants to a control condition, even for a short time, remains problematic. In stepped wedge trials, equipoise is likely to lie in the degree of effect, effectiveness in a specific operational milieu, and the balance of benefit and harm, including the social value of better evaluation. Third, the strongest arguments for a stepped wedge design are logistic and political rather than ethical. The design is advantageous when simultaneous roll-out is impractical and when it increases the acceptability of using counterfactuals. CONCLUSIONS: The logistic convenience of phased implementation is context-dependent, and may be vitiated by the additional requirements of phasing. The potential for stepped wedge trials to enhance the social acceptability of cluster randomised trials is real, but their ethical legitimacy still rests on demonstrating equipoise and its configuration for each research question and setting. PMID- 26278523 TI - Whole-Saliva Fluoride Levels and Saturation Indices in 65+ Elderly during Use of Four Different Toothpaste Regimens. AB - BACKGROUND: Elderly individuals suffering from subnormal saliva secretion combined with inadequate oral hygiene may develop rampant caries and caries in parts of the dentition not normally affected by caries if preventive measures are not undertaken. Such measures include elevating fluoride levels at the saliva/biofilm/tooth interface. AIM: To analyse whole-saliva fluoride levels and mineral saturation indices during different fluoride toothpaste regimens in home living elderly. MATERIALS AND METHODS: Whole saliva was collected from 27 subjects (7 males and 20 females, mean age 73.5+/-6.1 years) at ten time points covering the whole day during five 2-week periods. During the first period, participants used their normal toothpaste without instructions (baseline). This was followed by TP1: 1,450-ppm NaF toothpaste; TP2: 1,450-ppm monofluorophosphate (MFP) toothpaste with addition of calcium; TP3: 5,000-ppm NaF toothpaste, and TP4: the same toothpaste with additional 'smearing' of toothpaste on the teeth, twice daily. During TP1-TP4, the participants were instructed to brush 3 times per day using 1.5 g of toothpaste without rinsing. RESULTS: Salivary fluoride levels increased with toothpaste fluoride content (p<0.001), although major interindividual and intraindividual variations were observed. The highest fluoride values appeared in the morning and at night (p<0.001). Saturation indices for calcium fluoride were affected by the fluoride content in pastes (p<0.05). Concerning hydroxyapatite and fluorapatite, indices were highest with the MFP toothpaste and extra calcium (NS to p<0.05). CONCLUSIONS: Use of a high fluoride toothpaste resulted in significantly increased fluoride levels in whole saliva and mineral saturation indices were indeed influenced by choice of toothpaste. PMID- 26278524 TI - Delivery systems for biopharmaceuticals. Part II: Liposomes, Micelles, Microemulsions and Dendrimers. AB - Biopharmaceuticals are a generation of drugs that include peptides, proteins, nucleic acids and cell products. According to their particular molecular characteristics (e.g. high molecular size, susceptibility to enzymatic activity), these products present some limitations for administration and usually parenteral routes are the only option. To avoid these limitations, different colloidal carriers (e.g. liposomes, micelles, microemulsions and dendrimers) have been proposed to improve biopharmaceuticals delivery. Liposomes are promising drug delivery systems, despite some limitations have been reported (e.g. in vivo failure, poor long-term stability and low transfection efficiency), and only a limited number of formulations have reached the market. Micelles and microemulsions require more studies to exclude some of the observed drawbacks and guarantee their potential for use in clinic. According to their peculiar structures, dendrimers have been showing good results for nucleic acids delivery and a great development of these systems during next years is expected. This is the Part II of two review articles, which provides the state of the art of biopharmaceuticals delivery systems. Part II deals with liposomes, micelles, microemulsions and dendrimers. PMID- 26278525 TI - The Use of Nanocarriers in Acute Myeloid Leukaemia Therapy: Challenges and Current Status. AB - Chemotherapy for AML is hampered by severe side-effects and failure to eliminate all the blasts that eventually leads to relapse. The use of nanosized particulate drug carriers such as liposomes and polymeric nanoparticles has the potential to improve AML therapy by delivering more of the drug to the disease site, thereby reducing toxicity. For example, encapsulation in liposomes reduces the cardiotoxicity of anthracyclines, giving an improved therapeutic index. Moreover, when the surface properties are engineered appropriately, nanocarriers remain in the circulation and extravasate in tissues with sinusoidal capillaries, one of which is bone marrow, leading to a more favourable distribution of the associated drug. Drug carrier technology contributes to the development of newer drugs, such as nucleic acids that can be protected from degradation and delivered into cells, thus opening the way for gene-silencing strategies. Furthermore, carrier systems provide a means of dispersing poorly water-soluble molecule for in vivo administration and thus increase the "druggability" of new lead compounds, such as heat-shock protein inhibitors. Particulate carriers can transport more than one active agent, allowing synergistic action and theranostic strategies. Notably, phase I and II clinical trials are being performed with CPX-351, a liposomal formulation containing cytarabine and daunorubicin at an optimal ratio. Finally, by attaching suitable ligands to the nanocarrier surface, specific targeting to AML cells can be achieved. In this review, we give examples of successful targeting to folate and transferrin receptors against AML. PMID- 26278526 TI - Practical Considerations for Omics Experiments in Biomedical Sciences. AB - Modern analytical techniques provide an unprecedented insight to biomedical samples, allowing an in depth characterization of cells or body fluids, to the level of genes, transcripts, peptides, proteins, metabolites, or metallic ions. The fine grained picture provided by such approaches holds the promise for a better understanding of complex pathologies, and consequently the personalization of diagnosis, prognosis and treatment procedures. In practice however, technical limitations restrict the resolution of the acquired data, and thus of downstream biomedical inference. As a result, the study of complex diseases like leukemia and other types of cancer is impaired by the high heterogeneity of pathologies as well as patient profiles. In this review, we propose an introduction to the general approach of characterizing samples and inferring biomedical results. We highlight the main limitations of the technique with regards to complex and heterogeneous pathologies, and provide ways to overcome these by improving the ability of experiments in discriminating samples. PMID- 26278527 TI - Screening for Marine Natural Products with Potential as Chemotherapeutics for Acute Myeloid Leukemia. AB - Nature is an important source for anti-cancer therapeutics, and nearly half of the currently marketed cancer drugs are derived from natural products. Most of the therapeutic natural products are derived from terrestrial sources, such as paclitaxel, vincristine, epothilones, doxorubicin, etoposide and camptothecin. However, the oceans have received growing interest as a source for new useful bioactive compounds, and there are currently several drugs derived from marine natural products for the treatment of cancer on the market. The current recommended chemotherapy of acute myeloid leukemia (AML) is founded on cytarabine, a molecule derived from a natural product isolated from a marine sponge. However, in order to increase the efficiency of the chemotherapy used in the treatment of AML, it is necessary to develop more targeted drugs with less pronounced side effects. In this review, we argue that marine natural products have many of the desired properties of such a drug, and that prefractionated extract libraries of marine plants, animals and microorganisms should be a part of the screening efforts for new AML chemotherapeutics. PMID- 26278528 TI - Xenograft Models of Primary Acute Myeloid Leukemia for the Development of Imaging Strategies and Evaluation of Novel Targeted Therapies. AB - Despite the tremendous progress made in the comprehension of acute myeloid leukemia (AML) over the last 30 years most patients die from their disease. Our understanding of AML has relied on an intensive in-vitro research approach, based on AML cell lines as well as primary AML patient cells. However, experimental insight into the early events of AML leukemogenesis before they become clinically observable is not possible in humans. Thus, preclinical animal models have served the purpose to extend our knowledge of the disease as well as to develop innovative therapeutic strategies. Today, xenograft models using patient-derived neoplastic/leukemia cells represent the strategy of choice for preclinical studies of AML. These models exhibit several key advantages over AML cell lines. In fact, patient-derived cells, in contrast to AML cell lines, encompass the entire complexity of AML disease and can therefore provide more trustworthy results on the efficacy outcome of novel therapies. One other important aspect in the development of xenograft models of AML is the possibility to use imaging techniques to monitor in-vivo the progression of the disease. Imaging techniques also authorize the evaluation of the efficacy of an experimental treatment on tumor growth. This review will focus on the description of xenograft models of AML and will provide researchers and clinicians an overview of how these models have been used for the development of new therapeutic options and new imaging approaches to study AML in-vivo. PMID- 26278529 TI - Inhibition of Melanogenesis by Yeast Extracts from Cultivations of Recombinant Pichia pastoris Catalyzing ortho-Hydroxylation of Flavonoids. AB - The inhibition of melanogenesis by yeast extracts from cultivations of recombinant Pichia pastoris catalyzing ortho-hydroxylation of flavonoids was investigated. The recombinant yeast harbored a fusion gene composed of the CYP57B3 gene from Aspergillus oryzae and a cytochrome reductase gene from Saccharomyces cerevisiae. Ten flavonoids belonging to flavones, flavonols, flavanones, flavanols, and isoflavones were evaluated for biotransformation by the recombinant strain. The results showed that five flavonoids, including the flavone apigenin, the flavanones naringenin and liquiritigenin, and the isoflavones daidzein and genistein, could be biotransformed. The yeast extracts from the five biotransformation fermentations were then evaluated for inhibitory activity on melanogenesis in cultured mouse B16 melanoma cells. Three yeast extracts from biotransformation fermentation feeding with daidzein, genistein, or apigenin showed inhibitory activity on melanogenesis in the B16 cells, while the extract from genistein biotransformation exhibited the highest activity. The yeast extract from genistein biotransformation also showed inhibitory activity on cellular tyrosinase activity in the B16 cells. The present study shows a CYP with multiple flavonoid substrates for the first time and highlights the usage of yeast extracts from cultivations of the recombinant yeast catalyzing flavonoids' biotransformation in the development of skin-whitening agents. PMID- 26278530 TI - Synthesis, Self-assembly, and in vitro Biocompatibility of a Novel Steroidal Oxime. AB - A novel steroidal oxime (SO) was synthesized using an economic method and then characterized by Fourier transform infrared (FTIR) and 1H nuclear magnetic resonance (NMR). When dispersed in pure water, SO can self-assemble into a nano scale circular structure which was verified by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The formation of SO nano aggregates may result from its ambiphilic characteristic which has the hydrophobic cholesterolbased backbone and the hydrophilic oxime head group. The prepared SO aggregates were then examined for its in vitro biocompatibility using the human keratinocytes cell line (HaCaT) as a representative skin exposure model. The biocompatibility was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay and cell morphology observation. The results showed that the nano-scale SO aggregates did not cause serious damage to HaCaT cells at the designed concentrations and suggested that SO could be a potential material for preparing cosmeceutical carrier. PMID- 26278531 TI - N-(4-bromophenethyl) Caffeamide Inhibits Melanogenesis by Regulating AKT/Glycogen Synthase Kinase 3 Beta/Microphthalmia-associated Transcription Factor and Tyrosinase-related Protein 1/Tyrosinase. AB - Skin color is primarily produced by melanin, which is a crucial pigment that protects the skin from UV-induced damage and prevents carcinogenesis. However, accumulated melanin in the skin may cause hyperpigmentation and related disorders. Melanin synthesis comprises consecutive oxidative reactions, and tyrosinase is the enzyme that catalyzes the rate-limiting process of melanogenesis. In this study, tyrosinase-related protein 1 (TRP-1) and TRP-2 contributed to melanin formation. N-(4-bromophenethyl) caffeamide ((E)-N-(4 bromophenethyl)-3-(3,4-dihydroxyphenyl)acrylamide; K36H), a caffeic acid phenyl amide derivative, inhibited alpha-melanocyte-stimulating hormone (alpha-MSH) induced melanogenesis and tyrosinase activity in B16F0 cells. In addition, K36H reduced the protein expression of the phospho-cAMP response element binding protein (p-CREB), microphthalmia-associated transcription factor (MITF), tyrosinase, and TRP-1. Moreover, K36H promoted AKT and glycogen synthase kinase 3 beta (GSK3beta) phosphorylation, thereby inhibiting MITF transcription activity. Thus, K36H attenuated alpha-MSH-induced cAMP pathways, contributing to hypopigmentation. The results of a safety assay revealed that K36H did not exhibit cytotoxicity or irritate the skin or eyes. According to these results, K36H may have the potential to be used as a whitening agent in the cosmetic and pharmaceutical industries. PMID- 26278532 TI - A Review: Hair Health, Concerns of Shampoo Ingredients and Scalp Nourishing Treatments. AB - Human hair serves a biological purpose of protecting the scalp, as well as physical attractiveness to the perception of beauty. Hair loss, graying of hair, dandruff and other conditions affecting hair conditions can be distressing to patients, as hair condition is often considered important in people's own assessment of physical beauty. Different hair types can benefit from different treatment methods to promote hair health and growth. External factors like exposure to the sun and smoking, dietary factors including malnutrition of essential fatty acids and vitamins, and chemicals applied to the hair and scalp in shampoos and other treatments can all cause damage to existing hair and impair hair growth. Specific chemicals found in many shampoos, including antimicrobial agents, surfactants and preservatives, can all impair different aspects of hair health. In this review, we aim to discuss the main hair issues, such as hair loss, followed by the safety assessments of selected ingredients in shampoo, and possible nourishment for scalp improvement. This review highlights areas of disagreement in the existing literature, and points to new directions for future studies. Key conclusions include the carcinogenic chemicals to avoid, alternatives of such ingredients, and scalp nourishing treatments with micronutrients. PMID- 26278533 TI - Selection and optimization of transfection enhancer additives for increased virus like particle production in HEK293 suspension cell cultures. AB - The manufacturing of biopharmaceuticals in mammalian cells typically relies on the use of stable producer cell lines. However, in recent years, transient gene expression has emerged as a suitable technology for rapid production of biopharmaceuticals. Transient gene expression is particularly well suited for early developmental phases, where several potential therapeutic targets need to be produced and tested in vivo. As a relatively new bioprocessing modality, a number of opportunities exist for improving cell culture productivity upon transient transfection. For instance, several compounds have shown positive effects on transient gene expression. These transfection enhancers either facilitate entry of PEI/DNA transfection complexes into the cell or nucleus or increase levels of gene expression. In this work, the potential of combining transfection enhancers to increase Gag-based virus-like particle production levels upon transfection of suspension-growing HEK 293 cells is evaluated. Using Plackett-Burman design of experiments, it is first tested the effect of eight transfection enhancers: trichostatin A, valproic acid, sodium butyrate, dimethyl sulfoxide (DMSO), lithium acetate, caffeine, hydroxyurea, and nocodazole. An optimal combination of compounds exhibiting the highest effect on gene expression levels was subsequently identified using a surface response experimental design. The optimal consisted on the addition of 20 mM lithium acetate, 3.36 mM valproic acid, and 5.04 mM caffeine which increased VLP production levels 3.8-fold, while maintaining cell culture viability at 94%. PMID- 26278534 TI - Directed evolution to produce sludge communities with improved oxygen uptake abilities. AB - Two activated sludge cultures, seeded with activated sludge from the same source, were cultivated for 370 days in synthetic wastewater. Both cultures were transferred weekly to fresh medium; one culture was operated at high dissolved oxygen (DO) (near saturation) and the other at low DO (0.25 mg O2/L). There were significant changes in the abundances of bacterial species and phyla present in each culture throughout the 370-day operational period. In the low DO culture, over time, there was a continuously increasing proportion of cells of species known to encode truncated hemoglobins (Hbs). These are the types of Hbs which may enhance delivery of oxygen to the respiratory chain, to enhance ATP production, especially under low aeration conditions. The levels of heme b, the heme found in Vitreoscilla hemoglobin, increased in parallel to the increase in Hb-encoding species, to much higher levels in the low DO culture than in the high DO culture. Specific oxygen uptake rates increased by 3 % for the high DO culture near the end of the 370-day period, while those for the low DO culture increased steadily to a level 28 % higher than that of the starting culture. Thus, imposition of low DO conditions may, due to selection for Hb-expressing species, be useful in developing bacterial communities with enhanced ability to function efficiently in aerobic wastewater treatment, especially under low aeration conditions. PMID- 26278535 TI - Iron management and production of electricity by microorganisms. AB - The increasing dependency on fossil fuels has driven researchers to seek for alternative energy sources. Renewable energy sources such as sunlight, wind, or water are the most common. However, since the 1990s, other sources for energy production have been studied. The use of microorganisms such as bacteria or archaea to produce energy is currently in great progress. These present several advantages even when compared with other renewable energy sources. Besides the energy production, they are also involved in bioremediation such as the removal of heavy metal contaminants from soils or wastewaters. Several research groups have demonstrated that these organisms are able to interact with electrodes via heme and non-heme iron proteins. Therefore, the role of iron as well as iron metabolism in these species must be of enormous relevance. Recently, the influence of cellular iron regulation by Fur in the Geobacter sulfurreducens growth and ability to produce energy was demonstrated. In this review, we aim to briefly describe the most relevant proteins involved in the iron metabolism of bacteria and archaea and relate them and their biological function with the ability of selected organisms to produce energy. PMID- 26278536 TI - Identification of the antiphagocytic trypacidin gene cluster in the human pathogenic fungus Aspergillus fumigatus. AB - The opportunistic human pathogen Aspergillus fumigatus produces numerous different natural products. The genetic basis for the biosynthesis of a number of known metabolites has remained unknown. The gene cluster encoding for the biosynthesis of the conidia-bound metabolite trypacidin is of particular interest because of its antiprotozoal activity and possible role in the infection process. Here, we show that the genes encoding the biosynthesis enzymes of trypacidin reside within an orphan gene cluster in A. fumigatus. Genome mining identified tynC as an uncharacterized polyketide synthase with high similarity to known enzymes, whose products are structurally related to trypacidin including endocrocin and fumicycline. Gene deletion of tynC resulted in the complete absence of trypacidin production, which was fully restored when the mutant strain was complemented with the wild-type gene. When confronted with macrophages, the tynC deletion mutant conidia were more frequently phagocytosed than those of the parental wild-type strain. This was also found for phagocytic amoebae of the species Dictyostelium discoideum, which showed increased phagocytosis of DeltatynC conidia. Both macrophages and amoebae were also sensitive to trypacidin. Therefore, our results suggest that the conidium-bound trypacidin could have a protective function against phagocytes both in the environment and during the infection process. PMID- 26278537 TI - Cadmium resistance mechanism in Escherichia coli P4 and its potential use to bioremediate environmental cadmium. AB - A cadmium-resistant bacterium was isolated from industrial wastewater and identified as Escherichia coli (dubbed as P4) on the basis of morphological, biochemical tests and 16S rRNA ribotyping. It showed optimum growth at 30 degrees C and pH 7. E. coli P4 found to resist Cd(+2) (10.6 mM) as well as Zn(+2) (4.4 mM), Pb(+2) (17 mM), Cu(+2) (3.5 mM), Cr(+6) (4.4 mM), As(+2) (10.6 mM), and Hg(+2) (0.53 mM). It could remove 18.8, 37, and 56 % Cd(+2) from aqueous medium after 48, 96, and 144 h, respectively. Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), and Energy-dispersive X-ray (EDX) analysis also confirmed the biosorption of Cd(+2) by E. coli P4. However, temperature and pH were found to be the most critical factors in biosorption of Cd(+2) by E. coli P4. Cd(+2) stress altered E. coli P4 cell physiology analyzed by measuring glutathione (GSH) and non-protein thiol (cysteine) levels which were increased up to 130 and 48 %, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) showed alteration in the expression levels of ftsZ, mutS, clpB, ef-tu, and dnaK genes in the presence of Cd(+2). Total protein profiles of E. coli P4 in the absence and presence of Cd(+2) were compared by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), which showed remarkable difference in the banding pattern. czcB gene, a component of czcCBA operon, was amplified from genomic DNA which suggested the chromosomal borne Cd(+2) resistance in E. coli P4. Furthermore, it harbors smtAB gene which plays a significant role in Cd(+2) resistance. PMID- 26278539 TI - The role of mycorrhizal symbiosis in aluminum and phosphorus interactions in relation to aluminum tolerance in soybean. AB - Arbuscular mycorrhizal (AM) fungi protect plants against aluminum (Al) toxicity, but the mechanisms of Al and phosphorus (P) interactions in relation to Al tolerance in mycorrhizal plants are only poorly understood. In this study, varying Al and P treatments were applied to soybean plants cultivated in the presence or absence of three different AM fungi. The results showed that plants in symbiotic association with Gigaspora margarita displayed higher Al tolerance than Rhizophagus irregularis or Glomus claroideum. The effectiveness of G. margarita appeared to be associated with more abundant arbuscules and less affected intraradical hyphae compared to no Al controls. The highest levels of Al toxicity mitigation were observed with the combination of high P availability and AM fungal inoculation, which was associated with a concomitant increase in the expression of the AM-inducible phosphate (Pi) transporter gene GmPT9 in soybean. Taken together, these results suggest that AM symbiosis can alleviate Al toxicity in soybean through enhanced P nutrition, as well as, the alteration of the abundance of mycorrhizal infection structures. These findings highlight the importance of P nutrition status in ameliorating Al toxicity in mycorrhizal plants. PMID- 26278540 TI - The effects of upaB deletion and the double/triple deletion of upaB, aatA, and aatB genes on pathogenicity of avian pathogenic Escherichia coli. AB - Autotransporters (ATs) are associated with pathogenesis of Avian Pathogenic Escherichia coli (APEC). The molecular characterization of APEC ATs can provide insights about their relevance to APEC pathogenesis. Here, we characterized a conventional autotransporter UpaB in APEC DE205B genome. The upaB existed in 41.9 % of 236 APEC isolates and was predominantly associated with ECOR B2 and D. Our studies showed that UpaB mediates the DE205B adhesion in DF-1 cells, and enhances autoaggregation and biofilm formation of fimbria-negative E. coli AAEC189 (MG1655Deltafim) in vitro. Deletion of upaB of DE205B attenuates the virulence in duck model and early colonization in the duck lungs during APEC systemic infection. Furthermore, double and triple deletion of upaB, aatA, and aatB genes cumulatively attenuated DE205B adhesion in DF-1 cells, accompanying with decreased 50 % lethal dose (LD50) in duck model and the early colonization in the duck lungs. However, DE205BDeltaupaB/DeltaaatA/DeltaaatB might "compensate" the influence of gene deletion by upregulating the expression of fimbrial adhesin genes yqiL, yadN, and vacuolating autotransporter vat during early colonization of APEC. Finally, we demonstrated that vaccination with recombinant UpaB, AatA, and AatB proteins conferred protection against colisepticemia caused by DE205B infection in duck model. PMID- 26278538 TI - Omics on bioleaching: current and future impacts. AB - Bioleaching corresponds to the microbial-catalyzed process of conversion of insoluble metals into soluble forms. As an applied biotechnology globally used, it represents an extremely interesting field of research where omics techniques can be applied in terms of knowledge development, but moreover in terms of process design, control, and optimization. In this mini-review, the current state of genomics, proteomics, and metabolomics of bioleaching and the major impacts of these analytical methods at industrial scale are highlighted. In summary, genomics has been essential in the determination of the biodiversity of leaching processes and for development of conceptual and functional metabolic models. Proteomic impacts are mostly related to microbe-mineral interaction analysis, including copper resistance and biofilm formation. Early steps of metabolomics in the field of bioleaching have shown a significant potential for the use of metabolites as industrial biomarkers. Development directions are given in order to enhance the future impacts of the omics in biohydrometallurgy. PMID- 26278542 TI - Curcumin as an anti-human papillomavirus and anti-cancer compound. PMID- 26278541 TI - Heat-washout measurements compared to distal blood pressure and perfusion in orthopaedic patients with foot ulcers. AB - Distal blood pressure and local skin perfusion pressure were compared to measurement of blood flow rate (BFR) measured by the heat-washout method in orthopaedic patients with and without diabetes, all with a foot ulcer in one foot, compared to healthy controls. The correlation was good between heat-washout and distal blood pressure in patients with diabetes with and without an ulcer (P = 0.024 and 0.059, respectively). The correlation was weak in patients without diabetes with and without an ulcer, most probably due to power problems (P = 0.118 and 0.116, respectively). The correlation in the healthy controls was poor (P = 0.333 and 0.685 for right and left 1. Toe, respectively) probably because not all measurements were performed under optimal conditions with maximally dilated arterioles and warm hands and feet. The patients already have maximally dilated arterioles to extract the maximal amount of oxygen from the surrounding tissue, and therefore, measurements are easier made in these subjects. BFR in the first toe increased significantly in all patients when the foot was moved from heart level to 50 cm below heart level (P = between 0.03 and 0.05) as previously seen in patients with claudication. There was no statistical difference in the healthy controls, consistent with previous findings. These results may indicate that the heat-washout method can be used as an alternative to strain gauge blood pressure in the evaluation of peripheral artery disease and wound healing potentials. Furthermore, the heat-washout measurements can be used bedside. PMID- 26278543 TI - New evidence of a lateral transfer of monogenean parasite between distant fish hosts in Lake Ossa, South Cameroon: the case of Quadriacanthus euzeti n. sp. AB - Species of the monogenean genus Quadriacanthus mainly infect fish belonging to the Siluriformes, especially the genera Clarias, Heterobranchus or Bagrus, and their host specificity is strict (oioxenous) or narrow (stenoxenous). An examination of the gills of 19 Papyrocranus afer from Lake Ossa, South Cameroon, revealed for the first time the presence of a species of Quadriacanthus from a fish host belonging to the Notopteridae. The morphology and the size of sclerotized parts of haptor and the male and female copulatory complexes suggest that this monogenean is a new species named Quadriacanthus euzeti n. sp. The fish genus Papyrocranus differs taxonomically from the usual fish hosts of Quadriacanthus and hence the presence of a species belonging to this genus on the gills of this host suggests the occurrence of a lateral transfer of Quadriacanthus from species belonging to Clarias or Bagrus which live sympatrically with P. afer in Lake Ossa. PMID- 26278544 TI - Dipole antennas for ultrahigh-field body imaging: a comparison with loop coils. AB - Although the potential of dipole antennas for ultrahigh-field (UHF) MRI is largely recognized, they are still relatively unknown to the larger part of the MRI community. This article intends to provide electromagnetic insight into the general operating principles of dipole antennas by numerical simulations. The major part focuses on a comparison study of dipole antennas and loop coils at frequencies of 128, 298 and 400 MHz. This study shows that dipole antennas are only efficient radiofrequency (RF) coils in the presence of a dielectric and/or conducting load. In addition, the conservative electric fields (E-fields) at the ends of a dipole are negligible in comparison with the induced E-fields in the center. Like loop coils, long dipole antennas perform better than short dipoles for deeply located imaging targets and vice versa. When the optimal element is chosen for each depth, loop coils have higher B1 (+) efficiency for shallow depths, whereas dipole antennas have higher B1 (+) efficiency for large depths. The cross-over point depth decreases with increasing frequency: 11.6, 6.2 and 5.0 cm for 128, 298 and 400 MHz, respectively. For single elements, loop coils demonstrate a better B1 (+) /?SARmax ratio for any target depth and any frequency. However, one example study shows that, in an array setup with loop coil overlap for decoupling, this relationship is not straightforward. The overlapping loop coils may generate increased specific absorption rate (SAR) levels under the overlapping parts of the loops, depending on the drive phase settings. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26278545 TI - Samaras and seedlings of Acer pseudoplatanus are potential sources of hypoglycin A intoxication in atypical myopathy without necessarily inducing clinical signs. AB - REASONS FOR PERFORMING STUDY: Ingestion of sycamore seeds (Acer pseudoplatanus) is the likely source of hypoglycin A in atypical myopathy (AM) but ingestion of seedlings in spring might also contribute to intoxication. OBJECTIVES: To test for hypoglycin A in seeds and seedlings collected on pastures where AM cases were reported and compare its concentration in serum of affected and healthy horses. STUDY DESIGN: Field investigation of clinical cases. METHODS: Whenever present, samaras (the winged nuts that each contain one seed) and/or seedlings were collected from pastures of 8 AM cases and 5 unaffected horses from different premises. Two AM cases were each co-grazing with an apparently healthy horse. Acylcarnitines and hypoglycin A were quantified in blood samples of all horses involved in the study. RESULTS: Hypoglycin A was detected in serum of AM (5.47 +/ 1.60 MUmol/l) but not in healthy controls pasturing where A. pseudoplatanus trees were not present. However, hypoglycin A was detected at high concentrations (7.98 MUmol/l) in serum of a clinically healthy horse grazing a pasture with seedlings and samaras and also in the 2 healthy horses co-grazing with AM cases (0.43 +/- 0.59 MUmol/l). Hypoglycin A was detected in all samples of seeds and spring seedlings of A. pseudoplatanus. CONCLUSIONS: Atypical myopathy can be associated with the ingestion of sycamore samaras and also ingestion of seedlings. Hypoglycin A can be detected in the blood of horses with no detectable clinical signs at pasture in which there is A. pseudoplatanus. Determination of hypoglycin A concentration in blood is useful for screening for exposure in suspected cases of AM. PMID- 26278546 TI - Synergism of Curcumin and Cytarabine in the Down Regulation of Multi-Drug Resistance Genes in Acute Myeloid Leukemia. AB - BACKGROUND: The aim of the study was to find a role of Curcumin from natural source to overcome drug resistance as well as to reduce cytotoxicity profile of the drug in Acute Myeloid Leukemia patients. MATERIAL AND METHODS: Primary leukemic cells were obtained from AML patient's bone marrow. These cells were then exposed to different concentration of cytarabine and curcumin to find out IC50 values and also its effect on MDR genes like MDR1, BCRP, LRP and FLT3 by RT PCR method. RESULT & CONCLUSION: Our results suggested that curcumin down regulates MDR genes. Gene expression was decreased by 35.75, 31.30, 27.97 % for MDR1, LRP, BCRP respectively. In FLT3, it was 65.86 % for wild type and 31.79 % for FLT3-ITD. In addition to this, curcumin has also shown anti-proliferative effect as well as synergistic effect in combination with Cytarabine on primary leukemic cells. Thus, we can conclude that curcumin can be used as MDR modulator as well as chemosensitizer in combination with cytarabine, standard chemotherapeutic drug, to reduce the cytotoxicity profile as IC50 value decreases when treated in combination. PMID- 26278547 TI - Novel dibenzo[b,d]furan-1H-1,2,4-triazole derivatives: Synthesis and antitumor activity. AB - Twenty-four new dibenzo[b,d]furan-1H-1,2,4-triazole derivatives were synthesized and investigated for in vitro cytotoxic activity against five tumor cell lines. The results show that the substitution at 4-position of the 1,2,4-triazole with a benzyl, 4-bromophenacyl or naphthylacyl group could be crucial for prommoting cytotoxic activity. Especially, compound 28 was found to be the most powerful derivative with IC50 values lower than 3.50 MUM against five investigated tumor cell lines, while compound 19 showed selective activity against leukemia (HL-60) and breast carcinoma (MCF-7) cell lines with IC50 values of 0.80 and 1.76 MUM, respectively. Compound 19 can induce cell cycle arrest at G2/M phase and apoptosis in SMMC-7721 cells. PMID- 26278548 TI - A peptide-based pH-sensitive drug delivery system for targeted ablation of cancer cells. AB - A peptide-guided prodrug incorporating a tumor-specific peptide, doxorubicin, and a pH-sensitive hydrazone bridge was developed for targeted ablation of cancer cells with minimal side cytotoxicity. PMID- 26278549 TI - Faster Transport Status and Mortality in Anuric Patients Undergoing Continuous Ambulatory Peritoneal Dialysis. AB - BACKGROUND: There are limited data regarding the relationship between transport status and mortality in anuric continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: According to the dialysate to plasma creatinine ratio (D/P Cr), 292 anuric CAPD patients were stratified to faster (D/P Cr >=0.65) and slower transport groups (D/P Cr <0.65). The Cox proportional hazards models were used to evaluate the association of transport status with mortality. RESULTS: During a median follow-up of 22.1 months, 24% patients died, 61.4% of them due to cardiovascular disease (CVD). Anuric patients with faster transport were associated with an increased risk of all-cause mortality (HR (95% CI) = 2.16 (1.09-4.26)), but not cardiovascular mortality, after adjustment for confounders. Faster transporters with pre-existing CVD had a greater risk for death compared to those without any history of CVD. CONCLUSION: Faster transporters were independently associated with high all-cause mortality in anuric CAPD patients. This association was strengthened in patients with pre-existing CVD. PMID- 26278550 TI - Editorial for JoCI. PMID- 26278551 TI - Health-Related Quality of Life in Chronic Pruritus: An Analysis Related to Disease Etiology, Clinical Skin Conditions and Itch Intensity. AB - BACKGROUND: It is unknown if health-related quality of life (HRQoL) differs between diseases associated with chronic pruritus (CP). OBJECTIVE: To analyze HRQoL in relation to age, gender, skin lesions (primary vs. scratch-induced secondary) and itch intensity. METHODS: Consecutive patients of our itch clinic were assessed with the Dermatology Life Quality Index (DLQI) and visual analogue scale (VAS). RESULTS: In 510 CP patients (282 females; median age, 61.4 years), DLQI scores and VAS values were highly correlated, irrespective of the type of skin lesion. Overall, women had a lower HRQoL compared to men (females: 10.7 +/- 6.7, males: 8.9 +/- 6.7), but female gender was only associated with worse quality of life in patients <65 years old. CONCLUSION: HRQoL impairment in CP is highly influenced by pruritus intensity but not to the visible skin lesion or underlying cause. With limitations to item bias, DLQI is a suitable instrument for estimating quality of life impairment by CP. PMID- 26278552 TI - Large-Area Nano-patterning and Fabrication of Vertical Transistor Array by Non close-packed Polystyrene Spheres. AB - We demonstrated a large-area nanopatterning technique with the help of a non close-packed PS sphere layer over a large-area substrate. The non-close-packed PS sphere layer is fabricated by blade coating method. It was demonstrated that non close-packed PS spheres can be achieved within an area of 18 cm * 25 cm on a rigid glass substrate and within an area of 10 cm * 10 cm on a flexible substrate. We also demonstrated that the blade-coated non-close-packed PS sphere layer was suitable for the mass production of vertical organic transistors over a large area. PMID- 26278553 TI - Transmission Disequilibrium Tests Based on Read Counts for Low-Coverage Next Generation Sequence Data. AB - The purpose of this paper is the introduction of new statistical methods for case parent trio association studies based on the read counts that can be obtained from next-generation sequencing (NGS) experiments. This work focuses on the inclusion of low-coverage data into the case-parent trio design without genotype classification or imputation. Two different approaches are considered: (1) a likelihood-based approach implementing a 15-component parametric mixture model and (2) a model-free approach that applies non-parametric statistical methods to the ratios of the read counts to coverage. Simulation studies are conducted to evaluate the performances of the proposed tests. In addition, the non-centrality parameters of the mixture likelihood-based tests are derived to determine sample sizes and coverage for a NGS experimental design. As an example, the sample sizes to maintain specified powers of a published adolescent idiopathic scoliosis (AIS) study are presented. The simulation results show that the tests using the genotypes classified by the maximum Bayesian posterior probability have significantly inflated type I error rates for low-coverage data. The tests using the posterior probabilities instead of the classified genotypes show lower power than the proposed tests. Generally, power for the likelihood-based approach is higher than that for the non-parametric ratio-based approach. For the AIS example, approximately 654 trios with 4* coverage are necessary to maintain 90% power when detecting an association of odds ratio 2 at a locus with a minor allele frequency of 0.35 at the level of significance alpha = 5 * 10(-8). By comparison, approximately 416 trios with 25* coverage are required to maintain the same power with the same settings. The R and C source codes to calculate the proposed test statistics, the sample sizes and power can be obtained by contacting the author (wkim@cau.ac.kr). PMID- 26278554 TI - Necrotizing Enterocolitis in Preterm Pigs Is Associated with Increased Density of Intestinal Mucosa-Associated Bacteria Including Clostridium perfringens. AB - BACKGROUND: Necrotizing enterocolitis (NEC) is associated with changes in the luminal gut microbiota. It is not known whether the mucosa-associated microbiota is affected by NEC and stimulates inflammatory lesions. OBJECTIVE: We hypothesized that the density of the mucosa-associated microbiota correlates with NEC severity in preterm pigs and that in vitro infection with increasing densities of Clostridium perfringens, which has been associated with NEC in preterm infants, would lead to a transcriptional response related to the inflammatory conditions of NEC. METHODS: First, we determined the density of total bacteria and C. perfringens in the distal small intestinal mucosa of 58 NEC and healthy preterm pigs using quantitative PCR. Next, we analyzed in IPEC-J2 cells the effect of different infection densities of C. perfringens type A on the expression of genes related to intestinal function and immune response. RESULTS: Total bacterial and C. perfringens densities were higher in NEC versus healthy pigs and correlated positively with NEC severity. In IPEC-J2 cells expression levels of inflammation-related genes (CCL5, NFKBIA, IL8, IL1RN, and TNFAIP3) increased, while the expression of the sodium/glucose co-transporter (SLC5A1) decreased, with increasing density of C. perfringens. CONCLUSIONS: Total bacterial and C. perfringens densities were higher in NEC versus healthy pigs and correlated positively with NEC severity. In IPEC-J2 cells expression levels of inflammation-related genes (CCL5, NFKBIA, IL8, IL1RN, and TNFAIP3) increased, while the expression of the sodium/glucose co-transporter (SLC5A1) decreased, with increasing density of C. perfringens. PMID- 26278555 TI - Effects of apple pomace proportion levels on the fermentation quality of total mixed ration silage and its digestibility, preference and ruminal fermentation in beef cows. AB - Four Japanese black beef cows were used in a 4 * 4 Latin square to evaluate the fermentation quality, digestibility, ruminal fermentation and preference of total mixed ration (TMR) silages prepared with differing proportions of apple pomace (AP). Experimental treatments were the control (no AP added, CAP), 5% (low, LAP), 10% (medium, MAP) and 20% (high, HAP) of TMR dry matter (DM) as AP. All TMR silages were well preserved. Ethanol was produced in silages containing AP and the amount increased with the proportion of AP (P < 0.05). Nutrient digestibility with LAP, MAP and HAP treatment was lower than that with CAP treatment (P < 0.05). The ruminal molar proportion of acetic acid increased (P < 0.05), but the ruminal ammonia-N concentration decreased (P < 0.05) as the proportion of AP increased. The preference of the animals was highest for HAP, followed by MAP, CAP and LAP. This study demonstrates that decrease in nutrient digestibility might be related to the ethanol produced naturally from AP. Therefore, the proportion of AP in TMR silages should be less than 5% of dietary DM. PMID- 26278556 TI - Atypical Clinical Presentation of Xeroderma Pigmentosum in a Patient Harboring a Novel Missense Mutation in the XPC Gene: The Importance of Clinical Suspicion. AB - BACKGROUND: Xeroderma pigmentosum (XP) is a genodermatosis caused by abnormal DNA repair. XP complementation group C (XPC) is the most frequent type in Mediterranean countries. We describe a case with a novel mutation in the XPC gene. CASE: A healthy Caucasian male patient was diagnosed with multiple primary melanomas. Digital follow-up and molecular studies were carried out. RESULTS: During digital follow-up 8 more additional melanomas were diagnosed. Molecular studies did not identify mutations in CDKN2A, CDK4 or MITF genes. Two heterozygous mutations in the XPC gene were detected: c.2287delC (p.Leu763Cysfs*4) frameshift and c.2212A>G (p.Thr738Ala) missense mutations. CONCLUSION: The p.Thr738Ala missense mutation has not been previously described. Missense mutations in the XPC gene may allow partial functionality that could explain this unusual late onset XP. Atypical clinical presentation of XPC could be misdiagnosed when genetic aberrations allow partial DNA repair capacity. PMID- 26278557 TI - Porcine recombinant factor VIII (Obizur; OBI-1; BAX801): product characteristics and preclinical profile. AB - INTRODUCTION: Acquired haemophilia A (AHA) is a rare, often severe, auto-immune bleeding disorder caused by the development of inhibitory antibodies (inhibitors) to factor VIII (FVIII). Bypassing agents, recombinant activated FVII or activated prothrombin complex concentrate, are currently recommended as first-line treatments to control bleeding events in patients with AHA. AIM: A plasma-derived porcine FVIII (Hyate:C, Ipsen, UK) was used as a first-line treatment for AHA but was discontinued in 2004 due to viral safety concerns. A recombinant pFVIII (rpFVIII), Obizur (OBI-1; BAX801), which is expected to have a similar efficacy profile to Hyate:C but with a superior safety profile was developed and recently approved by the US Food and Drug Administration for the treatment of AHA. METHODS: Obizur manufacturing begins with the expression of B domain deleted rpFVIII by genetically modified baby hamster kidney-derived cells. The final purified and lyophilized drug product has a negligible risk of viral contamination and contains no animal-derived plasma proteins. Obizur was evaluated for immunogenicity, tolerability, pharmacokinetics and bleeding times in preclinical models including in haemophiliac dogs, cynomolgus monkeys and FVIII-knockout mice. RESULTS: Preclinical animal studies show that the efficacy and immunogenicity of Obizur are similar to that of Hyate:C and that Obizur has a more favourable safety profile. CONCLUSIONS: Obizur is a highly purified recombinant porcine FVIII drug product that has been demonstrated to have a favourable safety and efficacy profile when compared with Hyate:C and can be a valuable treatment option for control of bleeding in AHA patients. PMID- 26278559 TI - Editorial: novel association between serum Pentraxin-2 levels and advanced fibrosis in well-characterised patients with non-alcoholic fatty liver disease. PMID- 26278558 TI - Multidisciplinary assessment of patients with musical hallucinations, tinnitus and hearing loss. AB - BACKGROUND: Although auditory hallucinations are considered a psychopathological phenomenon, musical hallucinations have been reported in individuals without psychosis but with auditory symptoms (tinnitus and/or hearing loss). Thus, a possible different cognitive functioning may be involved in musical hallucinations. The aim of the study was to characterize patients with tinnitus and musical hallucinations through a multidisciplinary assessment, allowing a better understanding of these concomitant phenomena. SAMPLING AND METHODS: As this sample is rare to find, all consecutive patients with tinnitus, hearing loss and musical hallucinations were included over a 3-year period, excluding those unable to respond. All subjects underwent the following assessments: (1) otolaryngological and audiological assessment (physical examination and audiometry), (2) neurological assessment (cognition, electroencephalogram and imaging examination) and (3) psychiatric assessment (structured interview). RESULTS: A total of 16 patients were included (87.5% women; mean age 61.43 +/- 15.99 years). The otolaryngological examination was normal in all cases, but audiometry revealed that the degree of hearing loss was severe to profound in 68.75% of participants. Neurological assessment showed electroencephalogram changes in only 17.6% of cases, while 25% presented with mild attention deficit and 43.75% had small foci of gliosis or ischemia on the imaging examination. Psychiatric assessment showed that 68.75% of cases had depression, 6.25% had anxiety disorder and 25% had no psychiatric conditions. CONCLUSIONS: Musical hallucinations were strongly associated with female elderly adults and with mood disorders. Thus, in contrast to common auditory hallucinations, patients with musical hallucinations associated with tinnitus and hearing loss should be offered a more multidisciplinary assessment. PMID- 26278560 TI - Editorial: novel association between serum Pentraxin-2 levels and advanced fibrosis in well-characterised patients with non-alcoholic fatty liver disease- authors' reply. PMID- 26278561 TI - Editorial: predicting response to a low FODMAP diet in children. PMID- 26278562 TI - Editorial: predicting response to a low FODMAP diet in children--authors' reply. PMID- 26278563 TI - Letter: acute cholangitis--understanding predictors of outcome. PMID- 26278564 TI - Letter: acute cholangitis: understanding predictors of outcome--authors' reply. PMID- 26278565 TI - Letter: possible association between PPI use and spontaneous bacterial peritonitis. PMID- 26278566 TI - Letter: possible association of PPI use and spontaneous bacterial peritonitis- authors' reply. PMID- 26278567 TI - Letter: therapeutic trial is more informative than SeHCAT to diagnose bile acid malabsorption. PMID- 26278568 TI - Letter: therapeutic trial is more informative than SeHCAT to diagnose bile acid malabsorption--authors' reply. PMID- 26278569 TI - MiR-761 Promotes Progression and Metastasis of Non-Small Cell Lung Cancer by Targeting ING4 and TIMP2. AB - BACKGROUND/AIMS: The aim of this study was to investigate the role of microRNA miR-761 in the progression and metastasis of non-small cell lung cancer (NSCLC), and the mechanisms by which miR-761 regulates cell proliferation and metastatic activity of NSCLC cell lines. METHODS: Quantitative real-time PCR (qRT-PCR) was used to assess miR-761 expression in NSCLC serum and tissue. MTT, wound healing, and transwell assays were performed to examine the role of miR-761 in regulation of cell proliferation and metastatic activity in NSCLC cell lines. In addition, the correlations of miR-761 expression with clinical-pathologic factors were statistically analyzed. Finally, we investigated whether miR-761 promotes proliferation and metastasis in NSCLC cell lines by targeting ING4 (inhibitor of growth family, member 4) and TIMP2 (tissue inhibitor of metalloproteinase 2). RESULTS: MiR-761 was significantly upregulated in both NSCLC serum and tissues as compared to normal participants and paired noncancerous tissues respectively. Ectopic expression of miR-761 promoted cell proliferation and metastasis in H460 cells, while miR-761 inhibitor reduced proliferation rates and metastasis in H23 cells. Furthermore, luciferase reporter assay and functional analyses indicated that miR-761 directly targeted ING4 and TIMP2. CONCLUSION: miR-761 promotes progression and metastasis of NSCLC by targeting ING4 and TIMP2. PMID- 26278570 TI - Deletion 18p11.32p11.31 in a Child with Global Developmental Delay and Atypical, Drug-Resistant Absence Seizures. AB - We report the first case of an 18p11.32 deletion, detected by array CGH, associated with a drug-resistant form of atypical absence epilepsy, global developmental delay and no signs of holoprosencephaly (HPE). In particular, this region encompasses 19 genes, and none of these genes have been strictly associated with epilepsy. Among these, TGIF1 is expressed in the fetal and adult nervous system, and its deletion has been related to central nervous system diseases. TGIF1 deletions have previously been reported in patients with a comparable phenotype as seen in our case and in children whose neurological signs and symptoms were considerable, but not epileptiform. Mutations and deletions involving the TGIF1 gene have been described in patients with HPE in an autosomal dominant model of inheritance. However, TGIF1 mutations have also been reported in normal individuals and in patients with mental retardation or showing a very mild phenotype, suggesting the characteristic of incomplete penetrance and variable expressivity. Therefore, a TGIF1 deletion may not be always related to HPE, and it may have a link to the development of epilepsy. PMID- 26278571 TI - Editors' note. PMID- 26278576 TI - Ertapenem Prophylaxis Associated With an Increased Risk of Clostridium difficile Infection Among Surgical Patients. AB - A case-control study was conducted to determine risk factors for hospital-onset Clostridium difficile infection among patients admitted to 2 surgical units. Ertapenem prophylaxis was significantly associated with C. difficile infection risk (odds ratio, 3.13 [95% CI, 1.13-8.68], P=.028) and may offer an antimicrobial stewardship target among surgical patients. PMID- 26278577 TI - Second-Line Chemotherapy in Recurrent Glioblastoma--Still Controversial. PMID- 26278578 TI - Second-Line Chemotherapy in Recurrent Glioblastoma: A 2-Cohort Study. AB - BACKGROUND: Glioblastoma (GB) is the most common malignant primary central nervous system tumor in adults. Standard-of-care therapy includes surgical resection, radiotherapy and temozolomide, but nearly all patients experience disease progression. The purpose of this study was to describe 2 cohorts of patients with recurrent GB submitted to second-line treatment with procarbazine/lomustine/vincristine (PCV) or bevacizumab/irinotecan (BI). MATERIAL AND METHODS: Retrospective analysis of GB patients treated in our center with PCV or BI, after progression with temozolomide, between 2004 and 2012. RESULTS: Among 60 patients, 41 were treated with BI and 19 with PCV. According to the Macdonald criteria, the overall response rate in the BI group was 66% (n = 27) while it was 11% (n = 2) in the PCV group. The median progression-free survival was 5 and 3 months in the BI and PCV group, respectively. The median overall survival (OS) since second-line chemotherapy was 9 months in the BI group and 5 months in the PCV group. The latter group had a worse toxicity profile (grade 3-4: 52.6% vs. 22.0%; grade 1-2: 89.5% vs. 68.3%). CONCLUSIONS: The BI cohort had higher response rates, almost twice the OS and a lower degree of toxicity in contrast to the PCV group. The small number of patients and historical cohorts limits these comparisons. PMID- 26278579 TI - The German Version of the Herth Hope Index (HHI-D): Development and Psychometric Properties. AB - BACKGROUND: The importance of hope is evident in clinical oncological care. Hope is associated with psychological and also physical functioning. However, there is still a dearth of empirical research on hope as a multidimensional concept. The Herth Hope Index is a reliable and valid instrument for the measurement of hope and is available in many languages. Until now no authorized German translation has been published and validated. METHODS: After translation, the questionnaire was completed by 192 patients with different tumor entities in radiation therapy. Reliability, concurrent validity, and factor structure of the questionnaire were determined. RESULTS: Correlations were high with depression and anxiety as well as optimism and pessimism. As expected, correlations with coping styles were moderate. Internal consistency and test-retest reliability were satisfactory. We could not replicate the original 3-factor model. Application of the scree plot criterion in an exploratory factor analysis resulted in a single-factor structure. CONCLUSIONS: The Herth Hope Index - German Version (HHI-D) is a short, reliable, and valid instrument for the assessment of hope in patient populations. We recommend using only the HHI-D total score until further research gives more insights into possible factorial solutions and subscales. PMID- 26278580 TI - GAS5 Inhibits Gastric Cancer Cell Proliferation Partly by Modulating CDK6. AB - INTRODUCTION: As it is not clear whether growth arrest-specific 5 (GAS5) inhibits gastric cancer (GC) cell proliferation by regulating cell cycle, we analyzed the effect of GAS5 on cell cycle regulation of GC cells and explored the underlying mechanism. METHODS: We measured GAS5 levels in GC tissues and corresponding normal tissues, and analyzed the role of GAS5 in regulation of cell proliferation and cell cycle in GC cells using CCK-8 assay and flow cytometry. We also measured the expression of P21 and CDK6 proteins after transfection of AGS and MGC-803 cells with pLJM-GAS5 and GAS5 siRNA, respectively, by western blotting. RESULTS: GAS5 expression was significantly lower in GC tissues relative to normal tissues, and its lower expression was correlated with larger tumor size and a more advanced clinical stage of GC. GAS5 induced growth arrest of GC cells through inhibition of G1-S phase translation. The action of GAS5 may be mediated by upregulation of P21 and suppression of CDK6. CONCLUSION: These data enhance our understanding of the important role that GAS5 plays in the molecular etiology of GC and suggest a potential of GAS5 as a new therapeutic target for GC treatment. PMID- 26278581 TI - A Systematic Review of Adjuvant Interventions for Radioiodine in Patients with Thyroid Cancer. AB - AIMS: The purpose of this study was to assess the effects of adjuvant interventions for radioiodine in patients with thyroid cancer. MATERIALS AND METHODS: A systematic search was undertaken on July 9, 2014. RevMan 5 software was used to synthesize data. RESULTS: 13 randomized controlled trials were included. The pooled risk ratio of 0.99 (95% confidence interval (CI): 0.96-1.02, p = 0.58) indicated no significant difference in successful thyroid remnant ablation between recombinant human thyroid-stimulating hormone (rhTSH) and thyroid hormone withdrawal in 7 trials. The percentage of patients who had successful ablation was significantly higher in the oral-lithium group than in the control group (p = 0.017). A computerized decision aid improves informed decision-making in patients with early-stage papillary thyroid cancer (PTC) who are considering adjuvant radioiodine treatment (p < 0.001). Amifostine pretreatment did not prevent parenchymal damage to the major salivary gland function after radioiodine treatment (p = 0.2461). CONCLUSIONS: The present systematic review suggests that rhTSH, lithium, and computerized decision aids maybe act as beneficial adjuvant interventions for radioiodine in patients with thyroid cancer; however, amifostine does not exhibit helpful effects in thyroid cancer patients treated with radioiodine. PMID- 26278582 TI - Pretherapeutic Plasma Fibrinogen Level is an Independent Survival Predictor in Renal Cell Carcinoma. AB - BACKGROUND: Systematic inflammatory responses such as the elevated C-reactive protein, erythrocyte sedimentation rate and lymphocyte-monocyte ratio have been found to have significant prognostic value in renal cell carcinoma (RCC). The purpose of this study was to identify the impact of pretherapeutic plasma fibrinogen levels on survival for RCC patients. PATIENTS AND METHODS: We retrospectively reviewed 126 RCC patients who were treated at our institution. The median follow-up period was 30.8 months. 116 patients underwent nephrectomy. RESULTS: The 3-year overall survival rates in patients with non-metastatic or metastatic RCC were 91.9% and 14.3%, respectively (p < 0.001). Pretherapeutic plasma fibrinogen levels in the metastatic group were significantly higher than those in the non-metastatic group (p < 0.001). In the non-metastatic group, multivariate analysis revealed that the pathological T stage (p = 0.008), lactate dehydrogenase (p = 0.007) and fibrinogen (p = 0.036) were independent prognostic factors for survival. Overall survival rates in patients with low fibrinogen levels (< 399 mg/dl) were significantly higher than in those with high fibrinogen levels (>= 399 mg/dl). CONCLUSION: Pretherapeutic high plasma fibrinogen levels are associated with disease progression in patients with RCC of all stages. We propose that pretherapeutic plasma fibrinogen levels may become a useful biomarker, and could be helpful for decision making in the management of RCC. PMID- 26278583 TI - Disappearance of Upper Urinary Tract Urothelial Carcinoma after Treatment of a Borderline Brenner Tumor: Case Report and Literature Review. AB - BACKGROUND: Brenner tumors are relatively rare ovarian neoplasms with very few reported cases associating these tumors and urothelial carcinomas with different characteristics and particularities. CASE REPORT: We report an unusual clinical case of borderline unilateral Brenner tumor of the ovary associated with a highly recurrent diffuse low-grade papillary urothelial carcinoma of the upper and lower urinary tract. The patient received a total cystectomy and resection of the Brenner tumor. Her clinical response was marked by the absence of recurrence of the urothelial carcinoma and the disappearance of an untreated tumor of the upper urinary tract. The available literature on the association between these tumors was reviewed and their histologic appearance analyzed. CONCLUSION: The good prognosis of urothelial carcinoma in patients with Brenner tumors suggests different risk factors, physiopathologic features, and carcinogenesis than with typical urothelial carcinoma. PMID- 26278584 TI - Lack of Association between MDR1 G2677T/A Polymorphism and Leukemia Risk: An Updated Meta-Analysis. PMID- 26278586 TI - A new phylogenetic test for comparing multiple high-dimensional evolutionary rates suggests interplay of evolutionary rates and modularity in lanternfishes (Myctophiformes; Myctophidae). AB - The interplay between evolutionary rates and modularity influences the evolution of organismal body plans by both promoting and constraining the magnitude and direction of trait response to ecological conditions. However, few studies have examined whether the best-fit hypothesis of modularity is the same as the shape subset with the greatest difference in evolutionary rate. Here, we develop a new phylogenetic comparative method for comparing evolutionary rates among high dimensional traits, and apply this method to analyze body shape evolution in bioluminescent lanternfishes. We frame the study of evolutionary rates and modularity through analysis of three hypotheses derived from the literature on fish development, biomechanics, and bioluminescent communication. We show that a development-informed partitioning of shape exhibits the greatest evolutionary rate differences among modules, but that a hydrodynamically informed partitioning is the best-fit modularity hypothesis. Furthermore, we show that bioluminescent lateral photophores evolve at a similar rate as, and are strongly integrated with, body shape in lanternfishes. These results suggest that overlapping life history constraints on development and movement define axes of body shape evolution in lanternfishes, and that the positions of their lateral photophore complexes are likely a passive outcome of the interaction of these ecological pressures. PMID- 26278585 TI - Dialysis Facility Transplant Philosophy and Access to Kidney Transplantation in the Southeast. AB - BACKGROUND: Little is known about the impact of dialysis facility treatment philosophy on access to transplant. The aim of our study was to determine the relationship between the dialysis facility transplant philosophy and facility level access to kidney transplant waitlisting. METHODS: A 25-item questionnaire administered to Southeastern dialysis facilities (n = 509) in 2012 captured the facility transplant philosophy (categorized as 'transplant is our first choice', 'transplant is a great option for some', and 'transplant is a good option, if the patient is interested'). Facility-level waitlisting and facility characteristics were obtained from the 2008-2011 Dialysis Facility Report. Multivariable logistic regression was used to examine the association between the dialysis facility transplant philosophy and facility waitlisting performance (dichotomized using the national median), where low performance was defined as fewer than 21.7% of dialysis patients waitlisted within a facility. RESULTS: Fewer than 25% (n = 124) of dialysis facilities reported 'transplant is our first option'. A total of 131 (31.4%) dialysis facilities in the Southeast were high-performing facilities with respect to waitlisting. Adjusted analysis showed that facilities who reported 'transplant is our first option' were twice (OR 2.0; 95% CI 1.0-3.9) as likely to have high waitlisting performance compared to facilities who reported that 'transplant is a good option, if the patient is interested'. CONCLUSIONS: Facilities with staff who had a more positive transplant philosophy were more likely to have better facility waitlisting performance. Future prospective studies are needed to further investigate if improving the kidney transplant philosophy in dialysis facilities improves access to transplantation. PMID- 26278587 TI - Inference on cancer screening exam accuracy using population-level administrative data. AB - This paper develops a model for cancer screening and cancer incidence data, accommodating the partially unobserved disease status, clustered data structures, general covariate effects, and dependence between exams. The true unobserved cancer and detection status of screening participants are treated as latent variables, and a Markov Chain Monte Carlo algorithm is used to estimate the Bayesian posterior distributions of the diagnostic error rates and disease prevalence. We show how the Bayesian approach can be used to draw inferences about screening exam properties and disease prevalence while allowing for the possibility of conditional dependence between two exams. The techniques are applied to the estimation of the diagnostic accuracy of mammography and clinical breast examination using data from the Ontario Breast Screening Program in Canada. PMID- 26278588 TI - Platelets: Small in Size But Essential in the Regulation of Vascular Homeostasis Translation From Basic Science to Clinical Medicine. AB - Platelets are small blood cells that adhere to the site of vessel injury where von Willebrand factor (VWF) is expressed. Platelets bind to VWF through interaction with a membrane protein, glycoprotein (GP) Ibalpha. Next, the accumulated platelets are activated to change their morphological and biochemical characteristics. Various vasoactive substances, such as immune-regulatory CD40 ligand, are released locally from activated platelet cells to maintain homeostasis of the vascular system. Major roles played by platelets in the regulation of hemostasis and thrombus formation include local activation of the coagulation cascade. Translocation of negatively charged phospholipids to the surface of activated platelets helps in the formation of prothrombinase complex, which efficiently produces thrombin. Thrombin produces fibrin around the activated platelets and further activates the platelets through thrombin receptor stimulation. Of the various platelet-stimulating receptors and activation signals, cyclo-oxygenase-1, P2Y12 adenosine 5'-diphosphate receptor, and thrombin receptor (protease activated receptor)-1 blockers are used clinically as antiplatelet agents. In the future, precise understanding of the quantitative contribution of platelet function in hemostasis and pathological thrombus formation should lead to the development of effective antithrombotic agents without increasing the risk of serious bleeding complications. PMID- 26278589 TI - Correlates of women's knowledge of mother-to-child transmission of HIV and its prevention in Tanzania: a population-based study. AB - Studies that explored women's knowledge on mother-to-child transmission (MTCT) of HIV and its prevention (PMTCT) in the general population are currently lacking. This paper examined factors associated with having adequate knowledge of MTCT of HIV and PMTCT among a nationally representative sample of women in Tanzania. We conducted a cross-sectional analysis including 10,299 women from the 2011-2012 Tanzania HIV/AIDS and Malaria Indicator Survey. The outcome of interest was the presence of adequate knowledge on MTCT and PMTCT of HIV. We used multivariable logistic regression to identify factors associated with having adequate knowledge on MTCT and PMTCT of HIV. Results revealed that the overall prevalence of having adequate knowledge on MTCT and PMTCT of HIV was low (46%). We found a statistically significant difference in the proportions of having adequate knowledge between HIV-negative and HIV-positive women (45% vs. 56%; p < .0001), although knowledge of the transplacental route of transmission did not differ by HIV serostatus. Overall, having adequate knowledge on MTCT and PMTCT of HIV was positively associated with experiencing at least one pregnancy, having some education, having higher household wealth, residing in urban area, being exposed to HIV education, having tested for HIV, knowing a place to get HIV test, and having comprehensive knowledge on HIV and AIDS. Among HIV-seropositive women, experiencing at least one pregnancy and having comprehensive knowledge on HIV and AIDS were strongly associated with having adequate knowledge on MTCT and PMTCT of HIV (Adjusted odds ratio: aOR 2.78, 95% CI 1.21, 6.37 and aOR 1.71, 95% CI 1.15, 2.73, respectively). Further efforts are needed to enhance HIV/AIDS education among women of childbearing age and strengthen PMTCT services in Tanzania. PMID- 26278590 TI - Focused upon hybridization: rapid and high sensitivity detection of DNA using isotachophoresis and peptide nucleic acid probes. AB - We present a novel assay for rapid and high sensitivity detection of nucleic acids without amplification. Utilizing the neutral backbone of peptide nucleic acids (PNA), our method is based on the design of low electrophoretic mobility PNA probes, which do not focus under isotachophoresis (ITP) unless bound to their target sequence. Thus, background noise associated with free probes is entirely eliminated, significantly improving the signal-to-noise ratio while maintaining a simple single-step assay requiring no amplification steps. We provide a detailed analytical model and experimentally demonstrate the ability to detect targets as short as 17 nucleotides (nt) and a limit of detection of 100 fM with a dynamic range of 5 decades. We also demonstrate that the assay can be successfully implemented for detection of DNA in human serum without loss of signal. The assay requires 15 min to complete, and it could potentially be used in applications where rapid and highly sensitive amplification-free detection of nucleic acids is desired. PMID- 26278591 TI - Phosphate Binders and Clinical Outcomes in Patients with Stage 5D Chronic Kidney Disease. AB - Knowledge informing the prescription and the choice of phosphate binders in end stage kidney disease (ESKD) patients has a weak evidentiary base. To date, no placebo-controlled trial based on meaningful clinical endpoints (death, cardiovascular events, bone fractures) has been performed to test the efficacy of these drugs. By the same token, we still lack solid proof that noncalcium binders afford better clinical outcomes as compared with calcium-based binders. Without proper trials, clinical decisions about the treatment of hyperphosphatemia rest on experience and contingent clinical judgment. The use of huge doses of calcium based binders typically prescribed in the nineties now appears unwarranted. The relationship between phosphate and the risk of death is U shaped and moderate hyperphosphatemia carries just a mild-to-moderate risk excess and may not be seen as a compelling indication for the prescription of phosphate binders. Placebo controlled randomized clinical trials assessing whether non-calcium and calcium based binders reduce the risk of death and cardiovascular disease events in ESKD patients remain a public health priority. PMID- 26278592 TI - Impact of Intermolecular Distance on Singlet Fission in a Series of TIPS Pentacene Compounds. AB - Singlet fission has attracted considerable interest for its potential application in organic photovoltaics. However, the underlying microscopic mechanism is not well understood and the molecular parameters that govern SF efficiency remain unclear. We herein study the primary exciton photogeneration and evolution in the thin film of a series of pentacene derivatives (TIPS-Pn and ADPD-Pn) using femtosecond transient absorption spectroscopy. With a favorable "long-edge on" packing motif, the singlet-excited slip-stacked TIPS-Pn and ADPD-Pn molecules undergo ultrafast fission to produce triplet excitonic states with time constants of ~0.3 ps. More importantly, the ADPD-Pn compound features a considerably higher triplet yield than TIPS-Pn (162 +/- 10% vs 114 +/- 15%). The enhanced electronic coupling as a result of closer interchromophore distance (3.33 A for ADPD-Pn vs 3.40 A for TIPS-Pn) is suggested to account for the much higher triplet yield for ADPD-Pn relative to that for TIPS-Pn, proving SF can be readily modulated by adjusting the intermolecular distance. PMID- 26278593 TI - Iron-Treated NiO as a Highly Transparent p-Type Protection Layer for Efficient Si Based Photoanodes. AB - Sputter deposition of 50 nm thick NiO films on p(+)-n-Si and subsequent treatment in an Fe-containing electrolyte yielded highly transparent photoanodes capable of water oxidation (OER) in alkaline media (1 M KOH) with high efficiency and stability. The Fe treatment of NiO thin films enabled Si-based photoanode assemblies to obtain a current density of 10 mA/cm(2) (requirement for >10% efficient devices) at 1.15 V versus RHE (reversible hydrogen electrode) under red light (38.6 mW/cm(2)) irradiation. Thus, the photoanodes were harvesting ~80 mV of free energy (voltage), which places them among the best-performing Si-based photoanodes in alkaline media. The stability was proven by chronoamperometry at 1.3 V versus RHE for 300 h. Furthermore, measurements with electrochemical quartz crystal microbalances coupled with ICP-MS showed minor corrosion under dark operation. Extrapolation of the corrosion rate showed stability for more than 2000 days of continuous operation. Therefore, protection by Fe-treated NiO films is a promising strategy to achieve highly efficient and stable photoanodes. PMID- 26278594 TI - Nonlinear Density Dependence of Singlet Fission Rate in Tetracene Films. AB - Singlet fission holds the potential to dramatically improve the efficiency of solar energy conversion by creating two triplet excitons from one photoexcited singlet exciton in organic semiconductors. It is generally assumed that the singlet-fission rate is linearly dependent on the exciton density. Here we experimentally show that the rate of singlet fission has a nonlinear dependence on the density of photoexcited singlet excitons in tetracene films with small crystalline grains. We disentangle the spectrotemporal features of singlet and triplet dynamics from ultrafast spectroscopic data with the algorithm of singular value decomposition. The correlation between their temporal dynamics indicates a superlinear dependence of fission rate on the density of singlet excitons, which may arise from excitonic interactions. PMID- 26278595 TI - Porous Metal-Organic Frameworks for Gas Storage and Separation: What, How, and Why? AB - Metal-organic frameworks (MOFs) have been emerging as promising multifunctional materials and have shown particularly useful applications for gas storage and separation. We have briefly outlined the early development of this very active research field to provide us a clear picture on what are MOFs and how the research endeavor has been initiated and explored. Following that, we have demonstrated why MOFs are so unique for gas storage and separation: high porosities, tunable framework structures, and immobilized functional sites to fully make use of pore space for gas storage, to optimize their sieving effects, and to differentiate their interactions with gas molecules. Finally, we have provided a perspective on further development of porous MOFs for gas storage and separation. PMID- 26278596 TI - Quantum Dynamics of a Photochemical Bond Cleavage Influenced by the Solvent Environment: A Dynamic Continuum Approach. AB - In every day chemistry, solvents are used to influence the outcome of chemical synthesis. Electrostatic effects stabilize polar configurations during the reaction and in addition dynamic solvent effects can emerge. How the dynamic effects intervene on the ultrafast time scale is in the focus of this theoretical study. We selected the photoinduced bond cleavage of Ph2CH-PPh3(+) for which the electrostatic interactions are negligible. Elaborate ultrafast pump-probe studies already exist and serve as a reference. We compared quantum dynamical simulations with and without environment and noticed the necessity to model the influence of the solvent cage on the reactive motions of the solute. The frictional force induced by the dynamic viscosity of the solvent is implemented in the quantum mechanical formalism with a newly developed approach called the dynamic continuum ansatz. Only when the environment is included are the experimentally observed products reproduced on the subpicosecond time scale. PMID- 26278597 TI - Kinetics of Oxygen Reduction in Aprotic Li-O2 Cells: A Model-Based Study. AB - A comprehensive and general kinetic model is developed for the oxygen reduction reaction in aprotic Li-O2 cells. The model is based on the competitive uptake of lithium superoxide by the surface and solution. A demonstrative kinetic study is provided to demystify the origin of curvature in Tafel plots as well as the current dependency and aberrant diversity of the nature and morphology of discharge products in these systems. Our results are general and extend to any system where solubilization of superoxide is favored, such as where phase transfer catalysts play an important role. PMID- 26278598 TI - Does the 18-Electron Rule Apply to CrSi12? AB - Understanding the bonding between silicon and transition metals is valuable for devising strategies for incorporating magnetic species into silicon. CrSi12 is the standard example of a cluster whose apparent high stability has been explained by the 18-electron rule. We critically examine the bonding and nature of stability of CrSi12 and show that its electronic structure does not conform to the 18-electron rule. Through theoretical studies, we find that CrSi12 has 16 effective valence electrons assigned to the Cr atom and an unoccupied 3dz(2) orbital. We demonstrate that the cluster's apparent stability is rooted in a crystal field-like splitting of the 3d orbitals analogous to that of square planar complexes. CrSi14 is shown to follow the 18-electron rule and exhibits all conventional markers characteristic of a magic cluster. PMID- 26278599 TI - Correction to "Get the Basics Right: Jacobian Conversion of Wavelength and Energy Scales for Quantitative Analysis of Emission Spectra". PMID- 26278600 TI - Photoinduced Ultrafast Heterogeneous Electron Transfer at Molecule-Semiconductor Interfaces. AB - This Perspective discusses recent developments in ultrafast electron transfer dynamics at interfaces between organic and inorganic materials. Heterogeneous electron transfer (HET) is a key process in important fields like catalysis and solar energy conversion. Furthermore, the solid state nature of the systems gives control over relevant parameters and allows for investigating excited state dynamics and electron transfer processes in unprecedented detail. Progress in synthesis, sample preparation, and instrumentation makes it possible to provide experimental proof of recent prediction from theory concerning the adiabaticity of the reaction and the influence of coherence. A short recapitulation of the field is followed by a discussion of recent experimental efforts that allowed for studying HET, particularly focusing on the influence of energetics and vibrational dynamics. PMID- 26278602 TI - Mastering the Art of Scientific Publication. PMID- 26278601 TI - Quasiclassical Trajectory Calculations of the N((2)D) + H2O Reaction Elucidating the Formation Mechanism of HNO and HON Seen in Molecular Beam Experiments. AB - The N((2)D) + H2O is a reaction with competitive product channels, passing through several intermediates. Dynamics of this reaction had been investigated by two of the present authors at two collision energies, Ec, using the crossed molecular beams mass spectrometric method ( Faraday Discuss. 2001 , 119 , 27 - 49 ). The complicated mechanism of this reaction and puzzling results encouraged us to investigate the reaction in a joint experimental/theoretical study. Quasiclassical trajectory (QCT) calculations on an ab initio potential energy surface describing all channels of the title reaction are done with a focus on the N/H exchange channels. Interesting results of QCT calculations, in very good agreement with experimental data, reveal subtle details of the reaction dynamics of the title reaction to HNO/HON + H exit channels by disentangling the different routes to formation of the two possible HNO/HON isomers and therefore assisting in a critical manner the derivation of the reaction mechanism. Results of the present study show that the nonstatistical HNOH intermediate governs exit channels; therefore, the HON channel is as important as that of HNO. The study also confirms that the H2 + NO molecular channel is negligible even though the barrier to its formation is calculated to be well below the reactant asymptote. PMID- 26278603 TI - Hole Mobility in Nanocrystal Solids as a Function of Constituent Nanocrystal Size. AB - Solids of semiconductor nanocrystals (NCs) are semiconductors in which the band gap can be controlled by changing the size of the constituent NCs. To date, nontrivial dependencies of the carrier mobility on the NC size have been reported. We use the time-of-flight (TOF) technique to measure the carrier mobility as a function of the NC size and find that the hole mobility of the NC solid increases dramatically with decreasing NC radius. We show that this result is in agreement with an analytic model for carrier mobility in NC solids. We further implement Monte Carlo simulations to aid in understanding the transient measurements in the context of models of dispersive transport. This work highlights that changing NC size in a device has important implications for charge transport. PMID- 26278604 TI - Intramolecular H/D Exchange of Ethanol Catalyzed by Acidic OH Groups on H-ZSM-5 Zeolite. AB - IR observation of ethanol adsorption clarified the presence of the apparent intramolecular isotope exchange from CD3CH2OH to CHD2CH2OD on acidic OH groups of H-ZSM-5 zeolite. This reaction did not proceed with CD3OH nor CH3CD2OH, implying that the beta-hydrogen of alcohol had interaction with the lattice oxygen adjacent to Al and that the reaction was mediated by isotope exchange of CD3 groups of ethanol and OH groups on zeolite. PMID- 26278605 TI - Elusive Presence of Chloride in Mixed Halide Perovskite Solar Cells. AB - The role of chloride in the MAPbI3-xClx perovskite is still limitedly understood, albeit subjected of much debate. Here, we present a combined angle-resolved X-ray photoelectron spectroscopy (AR-XPS) and first-principles DFT modeling to investigate the MAPbI3-xClx/TiO2 interface. AR-XPS analyses carried out on ad hoc designed bilayers of MAPbI3-xClx perovskite deposited onto a flat TiO2 substrate reveal that the chloride is preferentially located in close proximity to the perovskite/TiO2 interface. DFT calculations indicate the preferential location of chloride at the TiO2 interface compared to the bulk perovskite due to an increased chloride-TiO2 surface affinity. Furthermore, our calculations clearly demonstrate an interfacial chloride-induced band bending, creating a directional "electron funnel" that may improve the charge collection efficiency of the device and possibly affecting also recombination pathways. Our findings represent a step forward to the rationalization of the peculiar properties of mixed halide perovskite, allowing one to further address material and device design issues. PMID- 26278607 TI - Effects of Electromagnetic Coupling on Conductance Switching of a Gated Tunnel Junction. PMID- 26278606 TI - Electrochemical Measurements of Single H2 Nanobubble Nucleation and Stability at Pt Nanoelectrodes. AB - Single H2 nanobubble nucleation is studied at Pt nanodisk electrodes of radii less than 50 nm, where H2 is produced through electrochemical reduction of protons in a strong acid solution. The critical concentration of dissolved H2 required for nanobubble nucleation is measured to be ~0.25 M. This value is ~310 times larger than the saturation concentration at room temperature and pressure and was found to be independent of acid type (e.g., H2SO4, HCl, and H3PO4) and nanoelectrode size. The effects of different surfactants on H2 nanobubble nucleation are consistent with the classic nucleation theory. As the surfactant concentration in H2SO4 solution increases, the solution surface tension decreases, resulting in a lower nucleation energy barrier and consequently a lower supersaturation concentration required for H2 nanobubble nucleation. Furthermore, amphiphilic surfactant molecules accumulate at the H2/solution interface, hindering interfacial H2 transfer from the nanobubble into the solution; consequently, the residual current decreases with increasing surfactant concentration. PMID- 26278608 TI - Concerted Thermal-Plus-Electronic Nonlocal Desorption of Chlorobenzene from Si(111)-7 * 7 in the STM. AB - The rate of desorption of chemisorbed chlorobenzene molecules from the Si(111)-7 * 7 surface, induced by nonlocal charge injection from an STM tip, depends on the surface temperature. Between 260 and 313 K, we find an Arrhenius thermal activation energy of 450 +/- 170 meV, consistent with the binding energy of physisorbed chlorobenzene on the same surface. Injected electrons excite the chlorobenzene molecule from the chemisorption state to an intermediate physisorption state, followed by thermal desorption. We find a second thermal activation energy of 21 +/- 4 meV in the lower temperature region between 77 and 260 K, assigned to surface phonon excitation. PMID- 26278609 TI - Probing the Nature of Charge Transfer at Nano-Bio Interfaces: Peptides on Metal Oxide Nanoparticles. AB - Characterizing the nano-bio interface has been a long-standing endeavor in the quest for novel biosensors, biophotovoltaics, and biocompatible electronic devices. In this context, the present computational work on the interaction of two peptides, A6K (Ac-AAAAAAK-NH2) and A7 (Ac-AAAAAAA-NH2) with semiconducting TiO2 nanoparticles is an effort to understand the peptide-metal oxide nanointerface. These investigations were spurred by recent experimental observations that nanostructured semiconducting metal oxides templated with A6K peptides not only stabilize large proteins like photosystem-I (PS-I) but also exhibit enhanced charge-transfer characteristics. Our results indicate that alpha helical structures of A6K are not only energetically more stabilized on TiO2 nanoparticles, but the resulting hybrids also exhibit enhanced electron transfer characteristics. This enhancement can be attributed to substantial changes in the electronic characteristics at the peptide-TiO2 interface. Apart from understanding the mechanism of electron transfer (ET) in peptide-stabilized PS-I on metal oxide nanoparticles, the current work also has implications in the development of novel solar cells and photocatalysts. PMID- 26278610 TI - Breaking Force and Conductance of Gold Nanojunctions: Effect of Humidity. AB - Forces acting on elongated gold nanojunctions and their electric conductance were simultaneously measured by current-sensing force spectroscopy in an atmosphere with controlled humidity. The breaking force of "thick" nanojunctions with conductance >20G0 is not affected by the environmental humidity. The presence of ambient water stabilizes "thin" nanojunctions with conductance <15G0, whose breaking force of 10-15 nN was higher than that in a dry atmosphere due to the capillary forces. The observed effect of humidity would not be possible to distinguish by techniques measuring only forces or only conductance in nanojunctions. PMID- 26278611 TI - Conditions for Directional Charge Transfer in CdSe Quantum Dots Functionalized by Ru(II) Polypyridine Complexes. AB - Thermodynamic conditions governing the charge transfer direction in CdSe quantum dots (QD) functionalized by either Ru(II)-trisbipyridine or black dye are studied using density functional theory (DFT) and time-dependent DFT (TDDFT). Compared to the energy offsets of the isolated QD and the dye, QD-dye interactions strongly stabilize dye orbitals with respect to the QD states, while the surface chemistry of the QD has a minor effect on the energy offsets. In all considered QD/dye composites, the dyes always introduce unoccupied states close to the edge of the conduction band and control the electron transfer. Negatively charged ligands and less polar solvents significantly destabilize the dye's occupied orbitals shifting them toward the very edge of the valence band, thus, providing favorite conditions for the hole transfer. Overall, variations in the dye's ligands and solvent polarity can progressively adjust the electronic structure of QD/dye composites to modify conditions for the directed charge transfer. PMID- 26278612 TI - Determination of Adsorbate Structures from 1,4-Phenylene Diisocyanide on Gold. AB - The structure of the 1-D oligomer chains that form on a Au(111) surface following adsorption of 1,4-phenylene diisocyanide (PDI) is explored using reflection absorption infrared spectroscopy and scanning tunneling microscopy (STM). The experimental work is complemented by first-principles density functional theory calculations, which indicate that the previously proposed gold-PDI oligomer chains in which the PDI molecule bridged gold adatoms are thermodynamically stable. In addition, the calculated vibrational modes for this structure are in excellent agreement with the experimental infrared data. The linkage of the PDI units by gold adatoms is confirmed by comparing STM images collected as a function of tip bias with images for the calculated structure by the Bardeen method. PMID- 26278613 TI - Modification of Hematite Electronic Properties with Trimethyl Aluminum to Enhance the Efficiency of Photoelectrodes. AB - The electronic properties of hematite were investigated by means of synchrotron radiation photoemission (SR-PES) and X-ray absorption spectroscopy (XAS). Hematite samples were exposed to trimethyl aluminum (TMA) pulses, a widely used Al-precursor for the atomic layer deposition (ALD) of Al2O3. SR-PES and XAS showed that the electronic properties of hematite were modified by the interaction with TMA. In particular, the hybridization of O 2p states with Fe 3d and Fe 4s4p changed upon TMA pulses due to electron inclusion as polarons. The change of hybridization correlates with an enhancement of the photocurrent density due to water oxidation for the hematite electrodes. Such an enhancement has been associated with an improvement in charge carrier transport. Our findings open new perspectives for the understanding and utilization of electrode modifications by very thin ALD films and show that the interactions between metal precursors and substrates seem to be important factors in defining their electronic and photoelectrocatalytic properties. PMID- 26278614 TI - Resonantly Enhanced Multiphoton Ionization Spectrum of the Neutral Green Fluorescent Protein Chromophore. AB - The photophysics of the green fluorescent protein is governed by the electronic structure of the chromophore at the heart of its beta-barrel protein structure. We present the first two-color, resonance-enhanced, multiphoton ionization spectrum of the isolated neutral chromophore in vacuo with supporting electronic structure calculations. We find the absorption maximum to be 3.65 +/- 0.05 eV (340 +/- 5 nm), which is blue-shifted by 0.5 eV (55 nm) from the absorption maximum of the protein in its neutral form. Our results show that interactions between the chromophore and the protein have a significant influence on the electronic structure of the neutral chromophore during photoabsorption and provide a benchmark for the rational design of novel chromophores as fluorescent markers or photomanipulators. PMID- 26278615 TI - Resolving Internal Motional Correlations to Complete the Conformational Entropy Meter. AB - Conformational entropy (SOmega) has long been used to theoretically characterize the dynamics of proteins, DNA, and other polymers. Though recent advances enabled its calculation also from simulations and nuclear magnetic resonance (NMR) relaxation experiments, correlated molecular motion has hitherto greatly hindered both numerical and experimental determination, requiring demanding empirical and computational calibrations. Herein, we show that these motional correlations can be estimated directly from the temperature-dependent SOmega series that reveal effective persistence lengths of the polymers, which we demonstrate by measuring SOmega of amphiphilic molecules in model lipid systems by spin-labeling electron paramagnetic resonance (EPR) spectroscopy. We validate our correlation-corrected SOmega meter against the basic biophysical interactions underlying biomembrane formation and stability, against the changes in enthalpy and diffusion coefficients upon phase transitions, and against the energetics of fatty acid dissociation. As the method can be directly applied to conformational analysis of proteins and other polymers, as well as adapted to NMR or polarized fluorescence techniques, we believe that the approach can greatly enrich the scope of experimentally available statistical thermodynamics, offering new physical insights into the behavior of biomolecules. PMID- 26278616 TI - Spectroscopic Demonstration of Exciton Dynamics and Excimer Formation in a Sterically Controlled Perylene Bisimide Dimer Aggregate. AB - Although it is commonly known that H-type PBI aggregates give rise to a broad, red-shifted excimer fluorescence with considerably longer fluorescence lifetimes than observed for the monomers, the underlying mechanisms of excimer formation and other relevant exciton dynamics in such pi-stacked systems are still far from being understood. In this context, we demonstrate a thorough spectroscopic investigation on the exciton relaxation pathways, including excimer formation, in a perylene-3,4:9,10-bis(dicarboximide) (PBI) dimer aggregate 1 by using time resolved fluorescence and transient absorption spectroscopy combined with excitation-power and polarization dependence. It was found that the excited dimer formation process followed by structural rearrangement is approximately two times faster than observed within larger PBI aggregates. Excitation-power-dependent transient absorption decay profiles revealed the fully delocalized nature of excitons in the dimer as opposed to larger stacks. PMID- 26278617 TI - A successful helium-neon laser and topical tacrolimus combination therapy in one child with vitiligo. PMID- 26278618 TI - The Difference in Maximum Standardized Uptake Value among Lung Adenocarcinomas Located at the Upper and Lower Zone on PET/CT. AB - BACKGROUND: Findings on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) are surrogate markers of malignancy in lung adenocarcinoma. Breathing during PET/CT can substantially reduce the maximum standardized uptake value (maxSUV) of lung tumors when they are located at the lower zone (LZ). OBJECTIVES: We assessed whether lung cancer location influences the malignancy predicted by maxSUV. METHODS: 608 patients with clinical stage IA lung adenocarcinoma had been preoperatively examined by PET/CT and high resolution computed tomography (HRCT). We evaluated the clinicopathological characteristics of these patients and the accuracy of precognition obtained by maxSUV between the upper zone (UZ, n = 395) and the LZ (n = 213). maxSUV was also analyzed for matched pairs between the two groups. RESULTS: The mean maxSUV in the LZ group was significantly lower than that in the UZ group (1.98 +/- 1.73 vs. 2.44 +/- 2.43, respectively; p = 0.0145). The receiver operating characteristics curve of maxSUV for predicting high-grade malignancy (lymphatic, vascular, pleural invasion, or lymph node metastasis) was larger for the UZ group than for the LZ group [0.89, 95% confidence interval (CI) 0.86-0.93, vs. 0.82, 95% CI 0.76 0.88]. Analysis for maxSUV of 213 pairs matched for the solid component size on HRCT, pathological characteristics, and gender revealed that maxSUV in the LZ group was significantly lower than that in the UZ group (1.98 +/- 1.73 vs. 2.47 +/- 2.39, respectively; p < 0.001). CONCLUSIONS: maxSUV of a tumor in the LZ group is apparently lower than the value which reflects the potential malignancy of a tumor. We have to carefully consider these facts when selecting the appropriate surgical procedure for lung cancer with PET/CT and HRCT. PMID- 26278619 TI - Generation of Subwavelength Plasmonic Nanovortices via Helically Corrugated Metallic Nanowires. AB - We demonstrate that plasmonic helical gratings consisting of metallic nanowires imprinted with helical grooves or ridges can be used efficiently to generate plasmonic vortices with radius much smaller than the operating wavelength. In our proposed approach, these helical surface gratings are designed so that plasmon modes with different azimuthal quantum numbers (topological charge) are phase matched, thus allowing one to generate optical plasmonic vortices with arbitrary topological charge. The general principles for designing plasmonic helical gratings that facilitate efficient generation of such plasmonic vortices are derived and their applicability to the conversion of plasmonic vortices with zero angular momentum into plasmonic vortices with arbitrary angular momentum is illustrated in several particular cases. Our analysis, based both on the exact solutions for the electromagnetic field propagating in the helical plasmonic grating and a coupled-mode theory, suggests that even in the presence of metal losses the fundamental mode with topological charge m = 0 can be converted to plasmon vortex modes with topological charge m = 1 and m = 2 with a conversion efficiency as large as 60%. The plasmonic nanovortices introduced in this study open new avenues for exciting applications of orbital angular momentum in the nanoworld. PMID- 26278620 TI - In vitro sliding-driven morphological changes in representative esthetic NiTi archwire surfaces. AB - OBJECTIVES: This study investigated the effects of sliding on the ultrastructure of three representative esthetic superelastic 0.014 inch nickel-titanium (NiTi) archwires. METHODS: Atomic force microscopy, scanning electron microscopy, and light microscopy were used to estimate the surface roughness of archwires and bracket systems. Energy-dispersive X-ray spectroscopy was used to estimate the molecular differences between coated and uncoated areas. A combination of four different types of 0.014 inch metallic wires and two different types of 0.022 inch * 0.028 inch conventional brackets were evaluated by in vitro sliding tests using a novel self-made tensile-strength tester with a miniature load cell and syringe pump. The NiTi wires included an uncoated NiTi archwire (CO group), epoxy resin-coated NiTi archwire (ER group), Teflon((r)) -coated NiTi archwire (TF group), and Ag/biopolymer-coated NiTi archwire (AG group). The brackets included contained stainless steel (SS) and ceramic (CE) brackets. RESULTS: Both ER and TF wire groups exhibited less surface roughness than CO wire groups. The AG group showed the highest surface roughness compared with the others because of its silver particles (P<0.001, ANOVA test). In vitro sliding tests led to a significant increase (P < 0.001, ANOVA test) in the surface roughness of all 0.014 inch NiTi wires regardless of bracket type. The wire groups combined with SS brackets were rougher than those of CE brackets regardless of the coating materials because of exfoliation of the coating materials. The TF-SS group showed the highest increase (fivefold) in surface roughness compared to the others, while the ER groups showed the lowest increase (1.4-fold) in surface roughness compared with the others (P < 0.001, ANOVA test). CONCLUSIONS: The results suggested that the sliding-driven surface roughness of superelastic NiTi archwires is directly affected by coating materials. Although the efficiency of orthodontic treatment was affected by various factors, epoxy resin-coated archwires were best for both esthetics and tooth movement when only considering surface roughness. PMID- 26278621 TI - Investigation of UV-emitting Gd(3+)-doped LiCaBO3 phosphor. AB - Incorporating the Gd(3+) rare earth ion in the LiCaBO3 host lattice resulted in narrow-band UV-B emission peaking at 315 nm, with excitation at 274 nm. The LiCaBO3:Gd(3+) phosphor was synthesized via the solid-state diffusion method. The structural, morphological and luminescence properties of this phosphor were characterized by X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM) and photoluminescence (PL) spectroscopy. Electron paramagnetic resonance (EPR) characterization of the as-prepared phosphors is also reported here. XRD studies confirmed the crystal formation and phase purity of the prepared phosphors. A series of different dopant concentrations was synthesized and the concentration-quenching effect was studied. Critical energy transfer distance between activator ions was determined and the mechanism governing the concentration quenching is also reported in this paper. PMID- 26278623 TI - The Effect of Telephone-Based Cognitive-Behavioral Therapy on Postnatal Depression: A Randomized Controlled Trial. AB - BACKGROUND: Cognitive-behavioral therapy (CBT) is one of the most effective interventions for postnatal depression. However, few studies have evaluated the effect of CBT delivered via telephone for newborn mothers. The purpose of this study was to evaluate the efficacy of telephone-based CBT for postnatal depression at 6 weeks and 6 months postpartum. METHODS: A multisite randomized controlled trial was conducted in the postnatal units at 3 regional hospitals in Hong Kong. A total of 397 women with an Edinburgh Postnatal Depression Scale (EPDS) score >=10 on the second or third day postpartum were randomized to receive telephone-based CBT (n = 197) or standard care (n = 200). Primary outcome was the total EPDS score. A cutoff score of 9/10 on the EPDS was used to define women at risk of postnatal depression. RESULTS: Telephone-based CBT was associated with significantly lower depressive symptoms compared with standard care, when assessed at 6 weeks postpartum in the subgroups of mothers with minor depression (EPDS 10-12; difference = 1.90, 95% CI: 0.72-3.08; p = 0.002) and major depression (EPDS >=13; difference = 5.00, 95% CI: 3.12-6.88; p < 0.001). The effect was sustained at 6 months postpartum in the subgroup with minor depression (difference = 1.20, 95% CI: 0.09-2.32; p = 0.034) but not significant in the subgroup with major depression (difference = 1.69, 95% CI: -0.10-3.47; p = 0.064). The proportion of women who satisfied our definition of postnatal depression was significantly lower in the intervention group at 6 weeks (difference = 23.3%, 95% CI: 13.7-33.0%; p < 0.001) and 6 months postpartum (difference = 11.4%, 95% CI: 1.9-20.8%; p = 0.019). CONCLUSIONS: Telephone-based CBT produced a significantly greater reduction in depressive symptoms than standard care during the postpartum period. PMID- 26278622 TI - Batf is important for IL-4 expression in T follicular helper cells. AB - Apart from T helper (Th)-2 cells, T follicular helper (Tfh) cells are a major class of IL-4-producing T cells, required for regulation of type 2 humoral immunity; however, transcriptional control of IL-4 production in Tfh cells remains mainly unknown. Here, we show that the basic leucine zipper transcription factor ATF-like, Batf is important for IL-4 expression in Tfh cells rather than in canonical Th2 cells. Functionally, Batf in cooperation with interferon regulatory factor (IRF) 4 along with Stat3 and Stat6 trigger IL-4 production in Tfh cells by directly binding to and activation of the CNS2 region in the IL-4 locus. In addition, Batf-to-c-Maf signalling is an important determinant of IL-4 expression in Tfh cells. Batf deficiency impairs the generation of IL-4-producing Tfh cells that results in protection against allergic asthma. Our results thus indicate a positive role of Batf in promoting the generation of pro-allergic IL-4 producing Tfh cells. PMID- 26278625 TI - Drift of dislocation tripoles under ultrasound influence. AB - Numerical simulations of dynamics of different stable dislocation tripoles under influence of monochromatic standing sound wave were performed. The basic conditions necessary for the drift and mutual rearrangements between dislocation structures were investigated. The dependence of the drift velocity of the dislocation tripoles as a function of the frequency and amplitude of the external influence was obtained. The results of the work can be useful in analysis of motion and self-organization of dislocation structure under ultrasound influence. PMID- 26278624 TI - Association of p21 3' UTR gene polymorphism with cancer risk: Evidence from a meta-analysis. AB - Numerous studies have investigated the risk of cancer associated with the polymorphism of p21 3' UTR (rs1059234 C > T), but results have been inconsistent. We performed this meta-analysis to drive a more precise estimation of the association between this polymorphism and risk of cancer. A comprehensive search was conducted to identify all case-control studies of the rs1059234 C > T polymorphism of p21 3' UTR and cancer susceptibility. A total of eleven eligible studies, including 3,099 cases and 4,354 controls, relating to the rs1059234 polymorphism of p21 3' UTR to the risk of cancer were identified. Multivariate and univariate methods revealed no association between this polymorphism and cancer risk. However, subgroup analysis by cancer type suggested that rs1059234 C > T polymorphism was associated with increased risk of squamous cell carcinoma of the head and neck (SCCHN) (dominant model CT + TT vs. CC: OR = 1.51, 95% CI = 1.17-1.94). No significant association was found in other subgroup analyses. This meta-analysis suggested that rs1059234 polymorphism of p21 3' UTR may be associated with increased SCCHN risk. And larger scale primary studies are required to further evaluate the interaction of p21 3' UTR rs1059234 polymorphism and cancer risk in specific populations. PMID- 26278627 TI - Results of the market-oriented reform in the Netherlands: a review. AB - The market-oriented reform in the Dutch health care system is now in its 10th year. This article offers a concise overview of some of its effects thus far on health insurance, healthcare purchasing and healthcare provision. Furthermore, attention is given to its impact on healthcare expenditures, power and trust relationships as well as the relationship between the Minister of Health and the Dutch Healthcare Authority. The reform triggered various alterations in Dutch health care some occurring quickly (e.g. health insurance), others taking longer (e.g. purchasing). These developments suggest a process of gradual transformation. The reform has instigated controversy which is increasingly framed as a power conflict between insurers and providers. Weakened consumer trust in insurers threatens the legitimacy of the reform. The relationship between Minister and Healthcare Authority appears to be more intimate than the formal independent status of this regulatory agency would suggest. PMID- 26278626 TI - Point mutations in KAL1 and the mitochondrial gene MT-tRNA(cys) synergize to produce Kallmann syndrome phenotype. AB - Kallmann syndrome (KS) is an inherited developmental disorder defined as the association of hypogonadotropic hypogonadism and anosmia or hyposmia. KS has been shown to be a genetically heterogeneous disease with different modes of inheritance. However, variants in any of the causative genes identified so far are only found in approximately one third of KS patients, thus indicating that other genes or pathways remain to be discovered. Here, we report a large Han Chinese family with inherited KS which harbors two novel variants, KAL1 c.146G>T (p.Cys49Phe) and mitochondrial tRNA(cys) (m.5800A>G). Although two variants can't exert obvious effects on the migration of GnRH neurons, they show the synergistic effect, which can account for the occurrence of the disorder in this family. Furthermore, the disturbance of the mitochondrial cysteinyl-tRNA pathway can significantly affect the migration of GnRH cells in vitro and in vivo by influencing the chemomigration function of anosmin-1. Our work highlights a new mode of inheritance underlay the genetic etiology of KS and provide valuable clues to understand the disease development. PMID- 26278628 TI - Separability criteria via sets of mutually unbiased measurements. AB - Mutually unbiased measurements (MUMs) are generalized from the concept of mutually unbiased bases (MUBs) and include the complete set of MUBs as a special case, but they are superior to MUBs as they do not need to be rank one projectors. We investigate entanglement detection using sets of MUMs and derive separability criteria for multipartite qudit systems, arbitrary high-dimensional bipartite systems of a d1-dimensional subsystem and a d2-dimensional subsystem, and multipartite systems of multi-level subsystems. These criteria are of the advantages of more effective and wider application range than previous criteria. They provide experimental implementation in detecting entanglement of unknown quantum states. PMID- 26278629 TI - Little evidence for morphological change in a resilient endemic species following the introduction of a novel predator. AB - Human activities, such as species introductions, are dramatically and rapidly altering natural ecological processes and often result in novel selection regimes. To date, we still have a limited understanding of the extent to which such anthropogenic selection may be driving contemporary phenotypic change in natural populations. Here, we test whether the introduction of the piscivorous Nile perch, Lates niloticus, into East Africa's Lake Victoria and nearby lakes coincided with morphological change in one resilient native prey species, the cyprinid fish Rastrineobola argentea. Drawing on prior ecomorphological research, we predicted that this novel predator would select for increased allocation to the caudal region in R. argentea to enhance burst-swimming performance and hence escape ability. To test this prediction, we compared body morphology of R. argentea across space (nine Ugandan lakes differing in Nile perch invasion history) and through time (before and after establishment of Nile perch in Lake Victoria). Spatial comparisons of contemporary populations only partially supported our predictions, with R. argentea from some invaded lakes having larger caudal regions and smaller heads compared to R. argentea from uninvaded lakes. There was no clear evidence of predator-associated change in body shape over time in Lake Victoria. We conclude that R. argentea have not responded to the presence of Nile perch with consistent morphological changes and that other factors are driving observed patterns of body shape variation in R. argentea. PMID- 26278630 TI - A lady with NASH and choreoathetosis. AB - We describe a case of acquired hepatocerebral degeneration (AHD) presenting with confusion and worsening memory problems since her discharge from the gastroenterology units. Cases of AHD are rare and are frequently confused with hepatic encephalopathy and Wilson's disease. There are no proven pharmacological therapies for AHD. Information regarding the effect of orthotopic liver transplant on AHD is limited and conflicting. Most patients eventually die from the systemic complications of cirrhotic liver failure including infection, hepatic coma and hepatocellular carcinoma. PMID- 26278631 TI - The Changing Face of Survival in Rett Syndrome and MECP2-Related Disorders. AB - PURPOSE: Survival in Rett syndrome remains unclear. Although early estimates were grim, more recent data suggest that survival into adulthood is typical. We aimed to define survival in Rett syndrome more clearly and identify risk factors for early death. METHODS: Participants with clinical Rett Syndrome or methyl-CpG binding protein 2 mutations without clinical RTT were recruited through the Rett Syndrome Natural History study from 2006 to 2015. Clinical details were collected, and survival was determined using the Kaplan-Meier estimator. Risk factors were assessed using Cox proportional hazards models. RESULTS: Among 1189 valid participants, 51 died (range 3.9-66.6 years) during the 9-year follow-up period. Those who died included 36 (3.9%) classic Rett syndrome females, 5 (5.9%) atypical severe Rett syndrome females, 1 (2.4%) non-Rett syndrome female, the single atypical severe male, 6 (30%) non-Rett syndrome males, and 2 (7.1%) methyl CpG-binding protein 2 duplication syndrome males. All atypical mild Rett syndrome females, methyl-CpG-binding protein 2 duplication syndrome females, and the single classic Rett syndrome male remain alive. Most deaths were due to cardiorespiratory issues. Only one died from severe malnutrition, scoliosis, and extreme frailty. Survival for classic and atypical Rett syndrome was greater than 70% at 45 years. Overall severity and several modifiable risk factors, including ambulation, weight, and seizures, were associated with mortality in classic Rett syndrome. CONCLUSIONS: Survival into the fifth decade is typical in Rett syndrome, and death due to extreme frailty has become rare. Although the leading cause of death remains cardiorespiratory compromise, many risk factors for early death are modifiable. Intense therapeutic interventions could further improve the prognosis for individuals with Rett syndrome. PMID- 26278632 TI - Neonatal Gabapentin Withdrawal Syndrome. AB - INTRODUCTION: Gabapentin, an anticonvulsant, neuroleptic, and pain medication, is widely used in both adults and children for management of epilepsy, bipolar illness, and neuropathic pain. Gabapentin use has also been recommended for hyperemesis gravidarum and restless leg syndrome in pregnant mothers. OBJECTIVE: Although gabapentin use is deemed safe during pregnancy, no clinical reports of gabapentin withdrawal syndrome in a neonate have been described. RESULTS: We present a newborn who showed signs of withdrawal after prolonged in utero exposure to gabapentin. CLINICAL IMPLICATIONS: Clinicians should be aware of possible withdrawal symptoms from drugs such as gabapentin, administered to mothers during pregnancy. We also encourage the gradual tapering of gabapentin in neonates over weeks to months similar to the adult population. PMID- 26278633 TI - Age-Related Ultrasound Changes in Muscle Quantity and Quality in Women. AB - This study investigated the age-related changes in muscle quantity and quality in the trunk and limbs of women. A total of 128 females were divided into four age groups: young, middle-aged, young-old and old-old. Muscle thickness (MT) and echo intensity (EI) of the biceps brachii, quadriceps femoris, rectus abdominis, external oblique, internal oblique and transversus abdominis were measured using B-mode ultrasonography. The EIs of the biceps brachii, quadriceps femoris and transversus abdominis were significantly higher in the middle-aged group than in the young group; however, there were no significant differences in MT. Compared with the young group, all other groups had significant changes in both MT and EI of the rectus abdominis, external oblique and internal oblique muscles. Thus, qualitative changes in muscle may occur earlier than quantitative changes, and loss of muscle mass may occur earlier in the superficial abdominal muscles than in the other muscles. PMID- 26278635 TI - Assessment of the Cervix in Pregnant Women Using Shear Wave Elastography: A Feasibility Study. AB - The quantitative assessment of the cervix is crucial for the estimation of pre term delivery risk and the prediction of the success of labor induction. We conducted a cross-sectional study using shear wave elastography based on the supersonic shear imaging technique. The shear wave speed (SWS) of the lower anterior part of the cervix was quantified over an 8-mm region of interest in 157 pregnant women. Cervical SWS is slightly but significantly reduced in patients diagnosed with pre-term labor and in patients who actually delivered pre-term. PMID- 26278634 TI - 4-D Assessment of Endometrial Vascularity Using Spatiotemporal Image Correlation: A Study Comparing Spherical Sampling and Whole-Tissue Analysis. AB - Our aim in the study described here was to assess the feasibility of spatiotemporal image correlation power Doppler quantification of the endometrium with two techniques: spherical samples and whole tissue. We scanned 51 women in the midluteal phase of the menstrual cycle: STIC assessment of the whole endometrium was not possible in 10% of cases, whereas spherical analysis was possible in all. The time taken for data set analysis was much longer for the whole endometrium compared with spherical analysis (1478.9 +/- 291 s vs. 266.8 +/ 39.3 s, p < 0.05). Intra-class correlation coefficients for the vascularization flow index (VFI) were similar for both methods. Volumetric vascularity indices were higher when spherical sampling was conducted. Significant cycle-to-cycle variability in the vascularity indices was present, with coefficients of variation exceeding 20% for both techniques. We found that STIC power Doppler quantification of the whole endometrium is possible in the majority of cases, however, it is time consuming and limited by significant cycle-to-cycle variability. PMID- 26278636 TI - Oncology nurses' communication challenges with patients and families: A qualitative study. AB - The benefits of effective communication in an oncology setting are multifold and include the overall well-being of patients and health professionals, adherence to treatment regimens, psychological functioning, and improvements in quality of life. Nevertheless, there are substantial barriers and communication challenges reported by oncology nurses. This study was conducted to present a summary of communication challenges faced by oncology nurses. From November 2012 to March 2014, 121 inpatient nurses working in the oncology setting participated in an online pre-training qualitative survey that asked nurses to describe common communication challenges in communicating empathy and discussing death, dying, and end-of-life (EOL) goals of care. The results revealed six themes that describe the challenges in communicating empathically: dialectic tensions, burden of carrying bad news, lack of skills for providing empathy, perceived institutional barriers, challenging situations, and perceived dissimilarities between the nurse and the patient. The results for challenges in discussing death, dying and EOL goals of care revealed five themes: dialectic tensions, discussing specific topics related to EOL, lack of skills for providing empathy, patient/family characteristics, and perceived institutional barriers. This study emphasizes the need for institutions to provide communication skills training to their oncology nurses for navigating through challenging patient interactions. PMID- 26278637 TI - Analysis of plasma microRNA expression profiles in male textile workers with noise-induced hearing loss. AB - BACKGROUND: Circulating microRNAs (miRNAs) have attracted interests as non invasive biomarkers of physiological and pathological conditions, which may be applied in noise-induced hearing loss (NIHL). However, no epidemiology studies have yet examined the potential effects of NIHL or noise exposure on miRNA expression profiles. OBJECTIVES: We sought to identify permanent NIHL-related miRNAs and to predict the biological functions of the putative genes encoding the indicated miRNAs. METHODS: In the discovery stage, we used a microarray assay to detect the miRNA expression profiles between pooled plasma samples from 10 noise exposed individuals with normal hearing and 10 NIHL patients. In addition, we conducted a preliminary validation of six candidate miRNAs in the same 20 workers. Subsequently, three miRNAs were selected for expanded validation in 23 non-exposed individuals with normal hearing and 46 noise-exposed textile workers which including 23 noise-exposed workers with normal hearing and 23 NIHL patients. Moreover, we predicted the biological functions of the putative target genes using a Gene Ontology (GO) function enrichment analysis. RESULTS: In the discovery stage, compared with the noise exposures with normal hearing, 73 miRNAs demonstrated at least a 1.5-fold differential expression in the NIHL patients. In the preliminary validation, compared with the noise exposures, the plasma levels of miR-16-5p, miR-24-3p, miR-185-5p and miR-451a were all upregulated (P < 0.001) in the NIHL patients. In the expanded validation stage, compared with the non exposures, the plasma levels of miR-24, miR-185-5p and miR-451a were all significantly downregulated (P < 0.001) in the exposures. And compared with the noise exposures, the plasma levels of miR-185-5p and miR-451a were slightly elevated (P < 0.001) in the NIHL patients, which were consistent with the results of preliminary validation and microarray analysis. CONCLUSION: The two indicated plasma miRNAs may be biomarkers of indicating responses to noise exposure. However, further studies are necessary to prove the causal association between miRNAs changes and noise exposure, and to determine whether these two miRNAs are clear biomarkers to noise exposure. PMID- 26278638 TI - Protective role of edaravone against cisplatin-induced ototoxicity in an auditory cell line. AB - Edaravone is a neuroprotective agent with a potent free radical scavenging and antioxidant actions. In the present study we investigated the influence of edaravone on cisplatin ototoxicity in auditory cells. Cell viability was determined using a 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide cell proliferation assay. Oxidative stress and apoptosis were assessed by reactive oxygen species (ROS) measurement, Hoechst 33258 staining, caspase-3 activity assay, and immunoblotting of PARP. Pretreatment with 100 MUM of edaravone prior to application of 15 MUM of cisplatin increased cell viability after 48 h of incubation in HEI-OC1 cells (from 51.9% to 64. 6% viability) and also, attenuated the cisplatin-induced increase in reactive oxygen species (ROS) (from 2.3 fold to 1.9 fold). Edaravone also decreased the activation of caspase-3 and reduced levels of cleaved poly-ADP-ribose polymerase (PARP). We propose that edaravone protects against cisplatin-induced ototoxicity by preventing apoptosis, and limiting ROS production in HEI-OC1 cells. PMID- 26278639 TI - Models of care involving district hospitals: a rapid review to inform the Australian rural and remote context. AB - OBJECTIVES: Distnct hospitals are important symbolic structures in rural and remote communities; however, little has been published on the role, function or models of care of district hospitals in rural and remote Australia. The aim of the present study was to identify models of care that incorporate district hospitals and have relevance to the Australian rural and remote context. METHODS: A systematic, rapid review was conducted of published peer-reviewed and grey literature using CINAHL, Medline, PsychInfo, APAIS-Health, ATSI health, Health Collection, Health & Society, Meditext, RURAL, PubMed and Google Scholar. Search terms included 'rural', 'small general and district hospitals', 'rural health services organisation & administration', 'medically underserved area', 'specific conditions, interventions, monitoring and evaluation', 'regional, rural and remote communities', 'NSW', 'Australia' and 'other OECD countries' between 2002 and 2013. Models of teaching and education, multipurpose services centres, recruitment and/or retention were excluded. RESULTS: The search yielded 1626 articles and reports. Following removal of duplicates, initial screening and full text screening, 24 data sources remained: 21 peer-reviewed publications and three from the grey literature. Identified models of care related specifically to maternal and child health, end-of-life care, cancer care services, Aboriginal health, mental health, surgery and emergency care. CONCLUSION: District hospitals play an important role in the delivery of care, particularly at key times in a person's life (birth, death, episodes of illness). They enable people to remain in or near their own community with support from a range of services. They also play an important role in the essential fabric of the community and the vertical integration of the health services. PMID- 26278640 TI - Oleuropein aglycone in lipid bilayer membranes. A molecular dynamics study. AB - Olive oil has been recognized to possess many therapeutic applications. Its beneficial effects arise from many causes, but one of them lies on the presence of oleuropein aglycone (OA). OA presents a plethora of pharmacological beneficial properties. Although there is a great research going on the effect of polyphenols and their derivatives on different aspects of health, much less knowledge is available of the molecular basis of their beneficial effects. Due to the prominent hydrophobic character of OA and its high phospholipid/water partition coefficient, some of its possible effects on biological systems might be related to its capacity to interact with and locate into the membrane. In this work we have aimed to locate the molecule of OA in two membrane model systems, i.e., POPC/Chol and POPC/POPG/Chol. OA locates in between the hydrocarbon acyl chains of the phospholipids but its specific location and molecular interactions differ depending on the lipid system. OA is nearer to the membrane surface in the POPC/Chol system but it is located at a deeper position in the POPC/POPG/Chol system. Furthermore, OA seems to interact stronger with POPG than with POPC, implying the existence of specific interactions with negatively-charged phospholipids. Some of the biological effects of OA could be due to its preferential location in the membrane depending on the membrane lipid composition as well as the existence of specific interactions with specific phospholipids. PMID- 26278641 TI - Pore-forming activity of clostridial binary toxins. AB - Clostridial binary toxins (Clostridium perfringens Iota toxin, Clostridium difficile transferase, Clostridium spiroforme toxin, Clostridium botulinum C2 toxin) as Bacillus binary toxins, including Bacillus anthracis toxins consist of two independent proteins, one being the binding component which mediates the internalization into cell of the intracellularly active component. Clostridial binary toxins induce actin cytoskeleton disorganization through mono-ADP ribosylation of globular actin and are responsible for enteric diseases. Clostridial and Bacillus binary toxins share structurally and functionally related binding components which recognize specific cell receptors, oligomerize, form pores in endocytic vesicle membrane, and mediate the transport of the enzymatic component into the cytosol. Binding components retain the global structure of pore-forming toxins (PFTs) from the cholesterol-dependent cytotoxin family such as perfringolysin. However, their pore-forming activity notably that of clostridial binding components is more related to that of heptameric PFT family including aerolysin and C. perfringens epsilon toxin. This review focuses upon pore-forming activity of clostridial binary toxins compared to other related PFTs. This article is part of a Special Issue entitled: Pore-Forming Toxins edited by Mauro Dalla Serra and Franco Gambale. PMID- 26278642 TI - Insight and analysis problem solving in microbes to machines. AB - A key feature for obtaining solutions to difficult problems, insight is oftentimes vaguely regarded as a special discontinuous intellectual process and/or a cognitive restructuring of problem representation or goal approach. However, this nearly century-old state of art devised by the Gestalt tradition to explain the non-analytical or non-trial-and-error, goal-seeking aptitude of primate mentality tends to neglect problem-solving capabilities of lower animal phyla, Kingdoms other than Animalia, and advancing smart computational technologies built from biological, artificial, and composite media. Attempting to provide an inclusive, precise definition of insight, two major criteria of insight, discontinuous processing and problem restructuring, are here reframed using terminology and statistical mechanical properties of computational complexity classes. Discontinuous processing becomes abrupt state transitions in algorithmic/heuristic outcomes or in types of algorithms/heuristics executed by agents using classical and/or quantum computational models. And problem restructuring becomes combinatorial reorganization of resources, problem-type substitution, and/or exchange of computational models. With insight bounded by computational complexity, humans, ciliated protozoa, and complex technological networks, for example, show insight when restructuring time requirements, combinatorial complexity, and problem type to solve polynomial and nondeterministic polynomial decision problems. Similar effects are expected from other problem types, supporting the idea that insight might be an epiphenomenon of analytical problem solving and consequently a larger information processing framework. Thus, this computational complexity definition of insight improves the power, external and internal validity, and reliability of operational parameters with which to classify, investigate, and produce the phenomenon for computational agents ranging from microbes to man-made devices. PMID- 26278643 TI - Dynamics of P53 in response to DNA damage: Mathematical modeling and perspective. AB - Cells are constantly challenged by intrinsic and extrinsic signals. DNA damage denotes a serious threat to cellular survival due to its extensive destroy to genomic integrity. Appropriate dynamic responses to changing signals are essential for homeostasis. The tumor suppressor p53 can respond to DNA damage and elicit diverse dynamical patterns. How signals and information are encoded and decoded in p53 network under DNA damaging stimuli are not fully understood. From theoretical perspective, we focus on the dynamical patterns of p53 and how such complex dynamics relate to cell fate leading to a better knowledge about its regulation and function. PMID- 26278644 TI - Mathematics and mysticism. AB - Is there a world of mathematics above and beyond ordinary reality, as Plato proposed? Or is mathematics a cultural construct? In this short article we speculate on the place of mathematical reality from the perspective of the mystical cosmologies of the ancient traditions of meditation, psychedelics, and divination. PMID- 26278645 TI - The mysterious connection between mathematics and physics. AB - The essay is in the form of a dialogue between the two authors. We take John Wheeler's idea of "It from Bit" as an essential clue and we rework the structure of the bit not to the qubit, but to a logical particle that is its own anti particle, a logical Marjorana particle. This is our key example of the amphibian nature of mathematics and the external world. We emphasize that mathematics is a combination of calculation and concept. At the conceptual level, mathematics is structured to be independent of time and multiplicity. Mathematics in this way occurs before number and counting. From this timeless domain, mathematics and mathematicians can explore worlds of multiplicity and infinity beyond the apparent limitations of the physical world and see that among these possible worlds there are coincidences with what is observed. PMID- 26278646 TI - The influence of prior novel androgen receptor targeted therapy on the efficacy of cabazitaxel in men with metastatic castration-resistant prostate cancer. AB - INTRODUCTION: The treatment armamentarium for metastatic castration-resistant prostate cancer (mCRPC) has expanded with the introduction of several new therapies. In this treatment continuum, it is unclear whether the efficacy of cabazitaxel is affected by prior novel androgen receptor targeted therapies (ART) such as abiraterone and enzalutamide. In this study, we investigated the influence of prior ART on the efficacy of cabazitaxel in men with mCRPC. PATIENTS AND METHODS: Data from an ongoing multicentre, phase II trial were used comprising 114 men with mCRPC treated with cabazitaxel in the post-docetaxel setting. The primary endpoints of the current analysis were prostate-specific antigen (PSA) response (? 50%), and overall survival (OS). Univariate and multivariable analyses were conducted to investigate the influence of prior ART on the efficacy of cabazitaxel. RESULTS: From the 114 patients included in this analysis, 44 men received prior ART and 70 men did not receive prior ART before treatment with cabazitaxel. PSA response rates while on cabazitaxel treatment were similar in patients with and without prior ART (34% versus 40%, respectively, P = 0.53). Likewise, median OS was not significantly different between men with and without prior ART (13.0 versus 14.0 months, respectively, logrank P = 0.65). In multivariable analysis, the only variables significantly associated with OS were performance status, serum albumin and alkaline phosphatase. CONCLUSION: Our study showed that prior treatment with ART may not influence the efficacy of cabazitaxel in men with mCRPC. With emerging evidence of cross-resistance in the treatment of mCRPC, cabazitaxel provides a good treatment option irrespective of prior ART. PMID- 26278647 TI - Non-invasive, serum DNA pregnancy testing leading to incidental discovery of cancer: a good thing? AB - Cell-free DNA for perinatal screening is a growing industry. Non-invasive prenatal testing (NIPT) is based on the premise that foetal DNA is able to cross the placental barrier and enter the mother's circulation, where it can be examined for chromosomal abnormalities, such as trisomy 13, 18 or 21. Such tests are expected to be widely used by pregnant women, with the annual market expected to surpass $1 billion. Recently, a number of case reports have emerged in the haematology-oncology literature. The routine use of NIPT has led to the discovery of maternal neoplasms. Most writers have concluded that this is yet another benefit of the test; however, a closer examination of the cases reveals that this incidental detection may not improve patient outcomes. In some cases, early detection provides lead time bias, but does not change the ultimate clinical outcome, and in other cases, detection constitutes earlier knowledge of a cancer whose natural history cannot be altered. Here, we explore in detail cases where cancer was incidentally discovered among women undergoing routine non-invasive pregnancy testing, and investigate whether or not these women were benefitted by the discovery. PMID- 26278648 TI - Uveal Melanoma UK National Guidelines. AB - The United Kingdom (UK) uveal melanoma guideline development group used an evidence based systematic approach (Scottish Intercollegiate Guidelines Network (SIGN)) to make recommendations in key areas of uncertainty in the field including: the use and effectiveness of new technologies for prognostication, the appropriate pathway for the surveillance of patients following treatment for primary uveal melanoma, the use and effectiveness of new technologies in the treatment of hepatic recurrence and the use of systemic treatments. The guidelines were sent for international peer review and have been accredited by NICE. A summary of key recommendations is presented. The full documents are available on the Melanoma Focus website. PMID- 26278649 TI - High subcutaneous adipose tissue predicts the prognosis in metastatic castration resistant prostate cancer patients in post chemotherapy setting. AB - BACKGROUND: Cancer studies have shown that body mass index (BMI), skeletal muscle mass (SMM) and adipose tissue indexes are linked to overall survival (OS) and progression-free survival (PFS). New treatments (abiraterone acetate, enzalutamide cabazitaxel, radium-223, sipuleucel-T) have improved patient outcomes in metastatic castration-resistant prostate cancer (mCRPC). Our objective was to analyse whether body composition parameters exert a prognostic role in mCRPC patients treated with next generation of androgen receptor (AR) axis inhibitors (abiraterone and enzalutamide). METHODS: All mCRPC patients from our institution who were enrolled in two prospective trials, assessing the efficacy of abiraterone acetate and the efficacy of enzalutamide, were selected. SMM, visceral and subcutaneous adipose tissue (SAT) indexes were assessed with computed tomography imaging by measuring cross-sectional areas of the tissues. RESULTS: In the 120 patients with available data, median OS and PFS were respectively: 16 months (95% confidence interval [CI] = 12-19) and 4 months (95% [CI] = 3-6). OS was associated with the SAT index: median survival was 15 months (95% [CI] 9-18) for patients with a SAT index < median value and 18 months (95% [CI] 13-30) for patients with a SAT index above (P = 0.008). In multivariate analyses, only the occurrence of visceral metastasis (P = 0.004), pain (P = 0.015) and SAT index (P = 0.036) were statistically significant predictors of OS. From baseline to 3 months, the SMM index loss was 2.49 +/- 0.44 cm(2)/m(2) (P < 0.001) corresponding to nearly 3.4 kg of muscle loss. CONCLUSIONS: High volume of SAT is independently associated with overall survival in mCRPC patients treated with next generation AR axis inhibitors. PMID- 26278650 TI - Prevalence and molecular typing of Giardia duodenalis in wildlife from eastern Poland. AB - Faecal samples from 162 wild animals were collected from 32 distinct sites of Leczynsko-Wlodawskie Lakeland (eastern Poland). The presence of Giardia duodenalis (Stiles, 1902) was assessed by a Direct Fluorescence Assay (DFA) and by Polymerase Chain Reaction (PCR) and sequencing of a fragment of the beta giardin gene. DFA showed the presence of cysts of G. duodenalis in 12 of 162 faecal samples (7%), namely in four wild boars (15%), four foxes (19%), two roe deer (4%), and two wolves (29%). PCR identified 34 of the 162 (21%) samples as positive, including 11 wild boars (41%), five red deer (18%), 11 roe deer (23%), four moose (17%), two wolves (29%) and a single sample from the European badger. Thus, PCR detected a significantly higher number of infection than DFA (P = 0.0005). However, 14 of 34 PCR products could not be sequenced because of their insufficient amount; the low number of cysts, poor conservation of the faeces or presence of PCR inhibitors may have contributed to weak DNA amplification. Sequence analysis of the remaining 20 products showed the presence of assemblage B in wild boars, red deer and roe deer, whereas samples from wolves were identified as assemblage D. This is the first detection of assemblage B in wild boars and deer. As assemblage B has zoonotic potential, wild animals from eastern Poland may act as reservoirs of cysts of G. duodenalis infectious for humans. PMID- 26278651 TI - Diagnostic accuracy of pace spikes in the electrocardiogram to diagnose paced rhythm. AB - OBJECTIVE: To determine how often cardiac resynchronization therapy (CRT) pacing systems generate visible pace spikes in the electrocardiogram (ECG). METHODS: In 46 patients treated with CRT pacing systems, we recorded ECGs during intrinsic rhythm, atrial pacing and ventricular pacing. ECGs were analysed for atrial and ventricular pace spikes by two experienced ECG readers blinded to the pacing therapy and to the study purpose. RESULTS: Atrial pacing generated visible pace spikes in less than 70% of the ECGs, whereas ventricular pacing generated visible pace spikes in about 90% of ECGs. The sensitivity of manual ECG interpretation for pace spikes was low for atrial pacing (Reader 1: 0.62 [95% confidence interval (CI) 0.50-0.74]; Reader 2: 0.65 [95% CI 0.53-0.77]) and moderate for ventricular pacing (Reader 1: 0.88 [95% CI 0.81-0.93]; Reader 2: 0.93 [95% CI 0.87-0.97]). CONCLUSIONS: In patients with CRT pacing systems, the absence of visible pace spikes in the ECG does not rule out paced rhythm. PMID- 26278652 TI - Direct endoscopic necrosectomy in retroflexion when using a lumen-apposing transmural covered metal stent. PMID- 26278653 TI - Drainage of obstructed gallbladder with use of lumen-apposing metal stent. PMID- 26278654 TI - EUS-guided liver biopsy for parenchymal disease: a comparison of diagnostic yield between two core biopsy needles. AB - BACKGROUND AND AIMS: EUS-guided biopsy of the liver has a variable diagnostic accuracy and specimen adequacy. A new core biopsy needle has been developed that may improve performance. The objective of this study was to compare the diagnostic yield of a new core biopsy needle with the previous standard needle. METHODS: In this cross-sectional study, consecutive patients who underwent EUS guided core liver biopsy over a 7-year period for suspected parenchymal disease were prospectively evaluated. Between 2007 and 2011, all biopsies were performed with a 19-gauge Tru-cut biopsy needle (Quick-core [QC]), whereas a novel reverse bevel needle (PC) was used exclusively from 2011 to 2014. All specimens were examined by 1 of 3 experienced, blinded pathologists for the following: presence of visible core, aggregate specimen length, number of complete portal tracts, and specimen adequacy. RESULTS: A total of 75 patients (mean age 51 years, 51 female) underwent liver biopsy by using the QC (n = 45) or PC (n = 30) needle. The QC and PC groups had similar demographics, indications for EUS, indications for liver biopsy, and liver findings on EUS. Compared with those of the QC, biopsies with the PC required fewer passes (median 2 vs 3; P < .0001) but produced longer aggregate length (median 20 mm vs 9 mm; P < .0001) with more complete portal tracts (median 5 vs 2; P = .0003) and adequate specimens (P < .01). Two patients had abdominal pain after liver biopsy with the QC needle. CONCLUSIONS: Compared with the QC needle, EUS-guided core liver biopsy with the PC needle produced longer aggregate length, more complete portal tracts, and more adequate specimens despite fewer passes (Clinical trial registration number: NCT00586313.). PMID- 26278655 TI - Endoscopic management of simultaneous Boerhaave's syndrome and malignant gastric outlet obstruction. PMID- 26278656 TI - Incision therapy for an unusual esophageal stricture. PMID- 26278657 TI - Suture Coding: A Novel Educational Guide for Suture Patterns. AB - OBJECTIVE: This study aims to provide a helpful guide to perform tissue suturing successfully using suture coding-a method for identification of suture patterns and techniques by giving full information about the method of application of each pattern using numbers and symbols. Suture coding helps construct an infrastructure for surgical suture science. It facilitates the easy understanding and learning of suturing techniques and patterns as well as detects the relationship between the different patterns. METHODS: Guide points are fixed on both edges of the wound to act as a guideline to help practice suture pattern techniques. The arrangement is fixed as 1-3-5-7 and a-c-e-g on one side (whether right or left) and as 2-4-6-8 and b-d-f-h on the other side. Needle placement must start from number 1 or letter "a" and continue to follow the code till the end of the stitching. Some rules are created to be adopted for the application of suture coding. A suture trainer containing guide points that simulate the coding process is used to facilitate the learning of the coding method. RESULTS: (120) Is the code of simple interrupted suture pattern; (ab210) is the code of vertical mattress suture pattern, and (013465)2/3 is the code of Cushing suture pattern. (0A1) Is suggested as a surgical suture language that gives the name and type of the suture pattern used to facilitate its identification. All suture patterns known in the world should start with (0), (A), or (1). There is a relationship between 2 or more surgical patterns according to their codes. CONCLUSIONS: It can be concluded that every suture pattern has its own code that helps in the identification of its type, structure, and method of application. Combination between numbers and symbols helps in the understanding of suture techniques easily without complication. There are specific relationships that can be identified between different suture patterns. Coding methods facilitate suture patterns learning process. CLINICAL RELEVANCE: The use of suture coding can be a good approach to the construction of an infrastructure of surgical suture science and the facilitation of the understanding and learning of suture pattern techniques. PMID- 26278658 TI - Tunable electronic and magnetic properties of monolayer MoS2 on decorated AlN nanosheets: a van der Waals density functional study. AB - In this study, structural, electronic, and magnetic properties of monolayer MoS2 on decorated AlN nanosheets have been systematically investigated using density functional theory with van der Waals corrections. The results indicate that the surface microstructure of the AlN substrate and stacking patterns significantly affect the electronic and magnetic properties of heterostructures. Moreover, the n type semiconductor to p type semiconductor to metal transition accompanied with the nonmagnetic to magnetic transfer can be achieved for monolayer MoS2. The diverse electronic and magnetic properties highlight the potential of MoS2 nanosheets for applications in electronics and spintronics. PMID- 26278659 TI - Intranasal immunization with protective antigen of Bacillus anthracis induces a long-term immunological memory response. AB - Although intranasal vaccination has been shown to be effective for the protection against inhalational anthrax, establishment of long-term immunity has yet to be achieved. Here, we investigated whether intranasal immunization with recombinant protective antigen (rPA) of Bacillus anthracis induces immunological memory responses in the mucosal and systemic compartments. Intranasal immunization with rPA plus cholera toxin (CT) sustained PA-specific antibody responses for 6 months in lung, nasal washes, and vaginal washes as well as serum. A significant induction of PA-specific memory B cells was observed in spleen, cervical lymph nodes (CLNs) and lung after booster immunization. Furthermore, intranasal immunization with rPA plus CT remarkably generated effector memory CD4(+) T cells in the lung. PA-specific CD4(+) T cells preferentially increased the expression of Th1- and Th17-type cytokines in lung, but not in spleen or CLNs. Collectively, the intranasal immunization with rPA plus CT promoted immunologic memory responses in the mucosal and systemic compartments, providing long-term immunity. PMID- 26278660 TI - Evaluation of Homobivalent Carbolines as Designed Multiple Ligands for the Treatment of Neurodegenerative Disorders. AB - Neurodegenerative diseases represent a challenge for biomedical research due to their high prevalence and lack of mechanism-based treatments. Because of the complex pathology of neurodegenerative disorders, multifunctional drugs have been increasingly recognized as potential treatments. We identified homobivalent gamma carbolinium salts as potent inihitors of both cholinesterases, N-methyl-D aspartate receptors, and monoamine oxidases. Homobivalent gamma-carbolines displayed similar structure-activity relationships on all tested targets and may present promising designed multiple ligands for the treatment of neurodegenerative disorders. PMID- 26278661 TI - Prophylactic laparoscopic cholecystectomy in adult sickle cell disease patients with cholelithiasis: A prospective cohort study. AB - INTRODUCTION: Prophylactic laparoscopic cholecystectomy remains controversial and has been discussed for selected subgroups of patients with asymptomatic cholelithiasis who are at high risk of developing complications such as chronic haemolytic conditions. Cholelithiasis is a frequent condition for patients with sickle cell disease (SCD). Complications from cholelithiasis may dramatically increase morbidity for these patients. Our objective was to evaluate the effectiveness of prophylactic cholecystectomy in SCD patients with asymptomatic gallbladder stones. METHODS: From January 2000 to June 2014, we performed 103 laparoscopic cholecystectomies on SCD patients. Fifty-two patients had asymptomatic cholelithiasis. The asymptomatic patients were prospectively enrolled in this study, and all underwent a prophylactic cholecystectomy with an intraoperative cholangiography. The symptomatic patients were retrospectively studied. Upon admission, all patients were administered specific perioperative management including intravenous hydration, antibiotic prophylaxis, oxygenation, and intravenous painkillers, as well as the subcutaneous administration of low molecular-weight heparin. During the same period, 51 patients with SCD underwent a cholecystectomy for symptomatic cholelithiasis. We compared these 2 groups in terms of postoperative mortality, morbidity, and hospital stay. RESULTS: There were no postoperative deaths or injuries to the bile ducts in either group. In the asymptomatic group, we observed 6 postoperative complications (11.5%), and in the symptomatic group, there were 13 (25.5%) postoperative complications. DISCUSSION: Regarding the SCD complications, we observed 1 case (2%) of acute chest syndrome in an asymptomatic cholelithiasis patient, while there were 3 cases (6%) in the symptomatic group. Vaso-occlusive crisis was observed in 1 patient (2%) with asymptomatic cholelithiasis, and in 4 patients (8%) in the other group. The mean hospital stay averaged 5.8 (4-17) days for prophylactic cholecystectomy and 7.96 (4-18) days for the comparative symptomatic group. CONCLUSIONS: Postoperative complications related to SCD were less frequent for asymptomatic patients who had a laparoscopic prophylactic cholecystectomy. This intervention, if performed with perioperative specific management, is safe and helps avoid emergency operations for acute complications including cholecystitis, choledocholithiasis, and cholangitis. For SCD patients, a prophylactic cholecystectomy reduces hospital stays. PMID- 26278662 TI - Adult liver transplantation in the congenital absence of inferior vena cava. AB - Whereas congenital absence of inferior vena cava observed in paediatric population more often than not, as an isolated or syndromic variety, this is seldom encountered in adult liver transplant recipients. There appear few sporadic reports in the literature on experience of such anomaly in adults. Given the rarity of situation, surprising encounters of such anomalies may pose challenge to the unprepared transplant surgeon and unfavourable outcomes may even have resulted in under-reportage of this condition. In this brief report we document our recent experience with two such cases and this is supplemented with extensive reference to the literature on classification of such anomalies with the endeavour to document implications of such in the adult liver transplant setting. PMID- 26278663 TI - Current status of pig lung xenotransplantation. AB - Human organ transplantation has improved duration and quality of life for many people, but its full potential is critically limited by short supply of available organs. One solution is xenotransplantation, although this comes with its own set of challenges. Lungs in particular are highly sensitive to injury, during the transplantation process generally, and to multiple immune rejection mechanisms. Using pig lung donors, our lab has been working on lung transplants into baboons as a surrogate for a human recipient. Several ex vivo human blood perfusion models have also proven useful. The combination of these experiments allows us to test large animal models as well as whole organ or isolated endothelial reactions to perfusion with human blood. We have found that a multi-modality therapeutic approach to prevent various pathogenic cascades - such as antibody-driven complement activation, other immune pathway activation, thrombosis, and tissue ischemia-reperfusion injury - has met with progressively greater success to protect the xeno lung from injury. Pig gene knockout and human gene transfer has been perhaps the greatest contributor. This review will discuss mechanisms of xeno lung injury, relevant experimental models, as well as recent results and future targets for research. PMID- 26278664 TI - Does single-port laparoscopic sleeve gastrectomy result in improved short-term perioperative outcomes compared to conventional multi-port laparoscopic sleeve gastrectomy? AB - A best evidence topic in bariatric surgery was written according to a structured protocol. The question asked whether single-port laparoscopic sleeve gastrectomy produces better short-term perioperative outcomes compared to the conventional multi-port laparoscopic sleeve gastrectomy in the treatment of morbid obesity. A Pubmed search generated 82 papers, 6 of which represented the best evidence to answer the clinical question. Of the 6, 1 paper was an updated analysis of the same patient cohort. The evidence on this subject is good. Five papers were level III, nonrandomized studies, 2 of which were prospective and 3 were retrospective cohort studies. The sixth paper was a level II, randomized, prospective study. We conclude that single-port laparoscopic sleeve gastrectomy results in less use of postoperative analgesia and better cosmetic satisfaction compared to multi-port laparoscopic sleeve gastrectomy in the short-term. The two groups showed comparable results in terms of mean operative time, mean hospitalization, and percentage excess weight loss. There was no difference in rate of postoperative complications including trocar site incisional hernia, staple line leaks, and bleeding. PMID- 26278665 TI - Evaluation of central pancreatectomy and pancreatic enucleation as pancreatic resections--A comparison. AB - INTRODUCTION: For minor pancreatic resection such as enucleation (PE) and central pancreatectomy (CP) comparative data are rare. These techniques provide parenchyma-sparing alternatives to major resections (e.g. pancreaticoduodenectomy) for neuroendocrine tumors, cystic tumors or metastases. This study retrospectively compares the morbidity and mortality of both techniques, with special regard to the formation of postoperative pancreatic fistulas (POPF). METHODS: Between December 1996 and November 2013 the postoperative events and clinical outcomes of 17 patients after pancreatic enucleation and 26 patients after central pancreatectomy were retrospectively analyzed from a prospectively collected database. RESULTS: Perioperative mortality was 0% in both groups. There was no significant difference in the overall peri-operative morbidity (CP 80.8% vs. PE 82.4%). The major cause of the high morbidity was the formation of a POPF with 26.9% of the patients after CP and 35.3% after PE. Univariate analysis showed a BMI over 30 kg/m(2) in the CP group to be an independent risk factor. Additional minor complications, e.g. urinary tract infection, pleural effusion, etc. furthermore contributed to the perioperative morbidity. CONCLUSION: PE and central CP are feasible techniques for selected patients, but the indications are limited. Morbidity after these resections is high with the major cause being the development of a POPF. PMID- 26278666 TI - Technical feasibility of sentinel lymph node biopsy in patients with ipsilateral breast tumor recurrence and previous axillary surgery. AB - INTRODUCTION: The role of sentinel lymph node biopsy (SLNB) in patients with ipsilateral breast tumor recurrence (IBTR) remains to be elucidated. The aim of this study was to evaluate feasibility and validity of SLNB in patients with IBTR. METHODS: A prospective database of 1172 patients with clinically node negative breast cancer who underwent SLNB from January 2005 to December 2013 at Keio University Hospital was analyzed and 35 patients with IBTR underwent SLNB. Sentinel lymph nodes (SLNs) were detected using a combined method of blue dye and radioisotope or indocyanine green fluorescence in cases with failure of identification by blue dye and radioisotope. RESULTS: Twenty-two patients had previous SLNB, eight had previous axillary lymph node dissection (ALND), and five had no previous axillary surgery. Overall, SLNs were successfully identified in 28 (80.0%) of 35 patients. The identification rate in patients with previous SLNB, ALND and no axillary surgery was 81.8% (18/22), 75% (6/8) and 80% (4/5), respectively (P = 0.52). Aberrant drainage outside the ipsilateral axilla was found more frequently in patients with previous ALND compared with SLNB and no axillary treatment (37.5% vs. 4.5% vs. 0%, P = 0.048). No axillary recurrence was observed after median follow-up of 40.3 months from the second surgery for IBTR. CONCLUSIONS: SLNB is a technically feasible and valid procedure for staging and treatment of regional lymph nodes in patients with IBTR. PMID- 26278667 TI - Analysis and reporting of stepped wedge randomised controlled trials: synthesis and critical appraisal of published studies, 2010 to 2014. AB - BACKGROUND: Stepped wedge cluster randomised trials introduce interventions to groups of clusters in a random order and have been used to evaluate interventions for health and wellbeing. Standardised guidance for reporting stepped wedge trials is currently absent, and a range of potential analytic approaches have been described. METHODS: We systematically identified and reviewed recently published (2010 to 2014) analyses of stepped wedge trials. We extracted data and described the range of reporting and analysis approaches taken across all studies. We critically appraised the strategy described by three trials chosen to reflect a range of design characteristics. RESULTS: Ten reports of completed analyses were identified. Reporting varied: seven of the studies included a CONSORT diagram, and only five also included a diagram of the intervention rollout. Seven assessed the balance achieved by randomisation, and there was considerable heterogeneity among the approaches used. Only six reported the trend in the outcome over time. All used both 'horizontal' and 'vertical' information to estimate the intervention effect: eight adjusted for time with a fixed effect, one used time as a condition using a Cox proportional hazards model, and one did not account for time trends. The majority used simple random effects to account for clustering and repeat measures, assuming a common intervention effect across clusters. Outcome data from before and after the rollout period were often included in the primary analysis. Potential lags in the outcome response to the intervention were rarely investigated. We use three case studies to illustrate different approaches to analysis and reporting. CONCLUSIONS: There is considerable heterogeneity in the reporting of stepped wedge cluster randomised trials. Correct specification of the time-trend underlies the validity of the analytical approaches. The possibility that intervention effects vary by cluster or over time should be considered. Further work should be done to standardise the reporting of the design, attrition, balance, and time-trends in stepped wedge trials. PMID- 26278668 TI - Cholinergic activation of the murine trachealis muscle via non-vesicular acetylcholine release involving low-affinity choline transporters. AB - In addition to quantal, vesicular release of acetylcholine (ACh), there is also non-quantal release at the motor endplate which is insufficient to evoke postsynaptic responses unless acetylcholinesterase (AChE) is inhibited. We here addressed potential non-quantal release in the mouse trachea by organ bath experiments and (immuno)histochemical methods. Electrical field stimulation (EFS) of nerve terminals elicited tracheal constriction that is largely due to ACh release. Classical enzyme histochemistry demonstrated acetylcholinesterase (AChE) activity in nerve fibers in the muscle and butyrylcholinesterase (BChE) activity in the smooth muscle cells. Acute inhibition of both esterases by eserine significantly raised tracheal tone which was fully sensitive to atropine. This effect was reduced, but not abolished, in AChE, but not in BChE gene-deficient mice. The eserine-induced increase in tracheal tone was unaffected by vesamicol (10(-5)M), an inhibitor of the vesicular acetylcholine transporter, and by corticosterone (10(-4)M), an inhibitor of organic cation transporters. Hemicholinium-3, in low concentrations an inhibitor of the high-affinity choline transporter-1 (CHT1), completely abrogated the eserine effects when applied in high concentrations (10(-4)M) pointing towards an involvement of low-affinity choline transporters. To evaluate the cellular sources of non-quantal ACh release in the trachea, expression of low-affinity choline transporter-like family (CTL1 5) was evaluated by RT-PCR analysis. Even though these transporters were largely abundant in the epithelium, denudation of airway epithelial cells had no effect on eserine-induced tracheal contraction, indicating a non-quantal release of ACh from non-epithelial sources in the airways. These data provide evidence for an epithelium-independent non-vesicular, non-quantal ACh release in the mouse trachea involving low-affinity choline transporters. PMID- 26278669 TI - Risk factors for bloodstream infections due to colistin-resistant KPC-producing Klebsiella pneumoniae: results from a multicenter case-control-control study. AB - The increasing prevalence of colistin resistance (ColR) Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (Kp) is a matter of concern because of its unfavourable impact on mortality of KPC-Kp bloodstream infections (BSI) and the shortage of alternative therapeutic options. A matched case-control control analysis was conducted. The primary study end point was to assess risk factors for ColR KPC-Kp BSI. The secondary end point was to describe mortality and clinical characteristics of these infections. To assess risk factors for ColR, 142 patients with ColR KPC-Kp BSI were compared to two controls groups: 284 controls without infections caused by KPC-Kp (control group A) and 284 controls with colistin-susceptible (ColS) KPC-Kp BSI (control group B). In the first multivariate analysis (cases vs. group A), previous colistin therapy, previous KPC-Kp colonization, >=3 previous hospitalizations, Charlson score >=3 and neutropenia were found to be associated with the development of ColR KPC-Kp BSI. In the second multivariate analysis (cases vs. group B), only previous colistin therapy, previous KPC-Kp colonization and Charlson score >=3 were associated with ColR. Overall, ColR among KPC-Kp blood isolates increased more than threefold during the 4.5-year study period, and 30-day mortality of ColR KPC-Kp BSI was as high as 51%. Strict rules for the use of colistin are mandatory to staunch the dissemination of ColR in KPC-Kp-endemic hospitals. PMID- 26278670 TI - Sarcoptes scabiei mites in humans are distributed into three genetically distinct clades. AB - Scabies is an ectoparasitic infestation caused by the mite Sarcoptes scabiei. Currently, S. scabiei is taxonomically divided into different varieties on the basis of host origin. Genetics-based research on scabies has been conducted, but the data on genetic diversity of populations of this mite in humans in Europe are lacking. We evaluated the genetic diversity of populations of S. scabiei. A large series of mites obtained from humans in France and the data of mites from various hosts and geographical areas retrieved from GenBank were included to investigate whether mites are divided into distinct populations. The study of cytochrome c oxidase subunit 1 gene polymorphisms were found to be best suited for phylogenetic analysis. S. scabiei mites were distributed into three genetically distinct clades, with most mites clustering in clades B and C. The Fst value and the Nm value calculated for mites included in clades B and C indicated a strong population structure and a very low gene flow between mites of those clades. The results of the present study not only support the rejection of the hypothesis of panmixia for S. scabiei in humans but also suggest that mites belonging to different clades are genetically isolated. Moreover, the results suggest that the subdivision of S. scabies in varieties according to animal or human hosts is not warranted. In conclusion, S. scabiei mites in humans do not constitute a homogeneous population. Further investigations are now required to assess whether different clinical forms of scabies are associated with particular haplotypes or clades. PMID- 26278671 TI - Diuretic effects of sodium-glucose cotransporter 2 inhibitor in patients with type 2 diabetes mellitus and heart failure. PMID- 26278672 TI - Effects of feeding omega-3-fatty acids on fatty acid composition and quality of bovine sperm and on antioxidative capacity of bovine seminal plasma. AB - The aim of the present study was to examine the effects of feeding alpha linolenic (ALA) acid on fatty acid composition and quality of bovine sperm and on antioxidative capacity of seminal plasma. Nine bulls (ALA bulls) were fed with 800 g rumen-resistant linseed oil with a content of 50% linolenic acid and eight bulls with 400 g palmitic acid (PA bulls). Sperm quality was evaluated for plasma membrane and acrosome intact sperm (PMAI), the amount of membrane lipid peroxidation (LPO), and the percentage of sperm with a high DNA fragmentation index (DFI). Fatty acid content of sperm was determined using gas chromatography. Total antioxidant capacity, glutathione peroxidase, and superoxide dismutase activity were determined in seminal plasma. Feeding ALA increased (P < 0.05) the docosahexaenoic acid (DHA) content in bulls whereas in PA bulls did not change. PMAI increased after cryopreservation in ALA bulls as well as in PA bulls during the experiment period (P < 0.005). LPO of sperm directly after thawing did not change during the study period in ALA group, but decreased in PA group (P < 0.006). After 3h of incubation LPO increased in the ALA group (P < 0.02), while LPO did not differ between phases within groups. In conclusion, feeding of neither saturated nor polyunsaturated fatty acids affect the antioxidant levels in seminal plasma. Both saturated as well as polyunsaturated fatty acids had positive effects on quality of cryopreserved bovine sperm, although the content of docosahexaenoic acid in sperm membranes increased only in ALA bulls. PMID- 26278673 TI - Phenotypic and functional heterogeneity of cancer-associated fibroblast within the tumor microenvironment. AB - Cancer microenvironment is created not only by malignant epithelial cells, but also by several kinds of stromal cells. Since Paget proposed the "seed and soil" hypothesis, the biological importance of the cancer microenvironment has come to be widely accepted. The main compartment of host stromal cells are fibroblasts (Cancer-Associated Fibroblasts; CAFs), which are the main source of the collagen producing cells. CAFs directly communicate with the cancer cells and other types of stromal cells to acquire a specific biological phenotype. CAFs play important roles in several aspects of the tumor progression process and the chemotherapeutic process. However, CAFs have heterogeneous origins, phenotypes, and functions under these conditions. A crucial challenge is to understand how much of this heterogeneity serves different biological responses to cancer cells. In this review, we highlight the issue of how diverse and heterogeneous functions given by CAFs can exert potent influences on tumor progression and therapeutic response. Furthermore, we also discuss the current advances in the development of novel therapeutic strategies against CAFs. PMID- 26278674 TI - Long-term follow-up of primary total hip arthroplasty with the Alloclassic Variall system. AB - PURPOSE: The aim of the present study was to evaluate the clinical and radiographic results of primary total hip arthroplasty (THA) performed with the Alloclassic Variall system (a modified version of the Alloclassic Zweymuller system) and to compare them with those in the literature for the original system. METHODS: Between January 2001 and December 2002, 273 consecutive primary THAs were performed in 259 patients at a single centre with the study system, using ceramic-on-ceramic (81.7 %) or ceramic-on-highly-crosslinked-polyethylene (18.3 %) articulations. RESULTS: At the time of this study, 28 patients (29 hips; 10.6 %) had died and 40 (43 hips; 15.8 %) were lost to follow-up. Seventeen patients (19 hips; 7.0 %) could be reached only by telephone. There were four revisions in four patients (1.5 %), all involving only the femoral component. Ten-year Kaplan Meier survival with revision of any component for any reason as the endpoint was 98.4 % (95 % confidence interval: 96.9-100 %; 30 hips remained 'at risk'). A total of 170 unrevised patients (178 hips; 65.2 %) were assessed clinically and radiographically at a median follow-up of 9.3 years (interquartile range [IQR] 8.8-9.8 years). The median Harris hip score (HHS) was 99.9 points (IQR 97.7-100). The score did not differ significantly between the two articulations. There was no sign of radiographic loosening. CONCLUSIONS: The ten-year implant survival and the HHS score outcomes for THAs performed with the novel system were in line with those documented in the literature for its predecessor. PMID- 26278676 TI - Periprosthetic fractures and complicated arthroplasties. PMID- 26278675 TI - Closed suction drainage has no benefits in revision total hip arthroplasty: a randomized controlled trial. AB - PURPOSE: Several studies have failed to show significant benefits of closed suction drainage (CSD) in routine primary total hip arthroplasty (THA). However, blood loss, haematoma formation and wound complications are generally much greater in revision THA as compared to primary THA. The purpose of this study was to determine if CSD is beneficial for revision THA patients. METHODS: We conducted a prospective, randomized, controlled trial at our institution between July 2013 and July 2014. Eighty-eight patients undergoing revision THA were enrolled and randomly assigned to receive a CSD (n = 44) or to not receive a CSD (n = 44). All first-stage revision surgeries for infection were excluded. Primary outcomes were haemoglobin loss and number of patients transfused. Secondary outcomes included functional outcome evaluated with Harris hip score (HHS), pain evaluated with visual analogue scale (VAS), and length of hospital stay. RESULTS: There were significantly more patients in the CSD group that required blood transfusions (20/44 as compared to 11/44, p = 0.04). Patients in the no CSD group were discharged earlier than patients in the CSD group (4.3 days as compared to 5.4 days, p = 0.002). No statistical significant difference was found in the HHS or pain VAS between the groups. CONCLUSIONS: This study did not demonstrate any benefit with the use of CSD for revision THA with regard to wound related complications, infection or early functional outcome. Post-operative blood loss, transfusion rate, and length of hospital stay may be higher with CSD. PMID- 26278677 TI - Rodentolepis straminea (Cestoda: Hymenolepididae) in an urban population of Apodemus sylvaticus in the UK. AB - The presence of the cyclophyllidean cestode Rodentolepis straminea (Cestoda: Hymenolepididae), was confirmed by molecular DNA analysis from a wood mouse (Apodemus sylvaticus) population inhabiting urban woodland in Salford, Greater Manchester (UK) with a prevalence of 27.8%. It would appear that the only previously published record of this species in A. sylvaticus in the British Isles is that from south-west Ireland, where 24% of the wood mice examined were infected with R. straminea. This species has been recorded in studies on A. sylvaticus in continental Europe. The current report represents a new record for R. straminea on mainland Britain and a first study of helminth parasites in an urban wood mouse population. PMID- 26278678 TI - Effects of pharmaceuticals present in aquatic environment on Phase I metabolism in fish. AB - The fate of pharmaceuticals in aquatic environments is an issue of concern. Current evidence indicates that the risks to fish greatly depend on the nature and concentrations of the pharmaceuticals and might be species-specific. Assessment of risks associated with the presence of pharmaceuticals in water is hindered by an incomplete understanding of the metabolism of these pharmaceuticals in aquatic species. In mammals and fish, pharmaceuticals are primarily metabolized by cytochrome P450 enzymes (CYP450). Thus, CYP450 activity is a crucial factor determining the detoxification abilities of organisms. Massive numbers of toxicological studies have investigated the interactions of human pharmaceuticals with detoxification systems in various fish species. In this paper, we review the effects of pharmaceuticals found in aquatic environments on fish hepatic CYP450. Moreover, we discuss the roles of nuclear receptors in cellular regulation and the effects of various groups of chemicals on fish, presented in the recent literature. PMID- 26278680 TI - Generic model for tunable colloidal aggregation in multidirectional fields. AB - Based on Brownian Dynamics computer simulations in two dimensions we investigate aggregation scenarios of colloidal particles with directional interactions induced by multiple external fields. To this end we propose a model which allows continuous change in the particle interactions from point-dipole-like to patchy like (with four patches). We show that, as a result of this change, the non equilibrium aggregation occurring at low densities and temperatures transforms from conventional diffusion-limited cluster aggregation (DLCA) to slippery DLCA involving rotating bonds; this is accompanied by a pronounced change of the underlying lattice structure of the aggregates from square-like to hexagonal ordering. Increasing the temperature we find a transformation to a fluid phase, consistent with results of a simple mean-field density functional theory. PMID- 26278679 TI - Synergistic effect of curcumin and piperine in suppression of DENA-induced hepatocellular carcinoma in rats. AB - Curcumin has been reported to suppress different types of clinical and experimentally-induced tumors, but due to less absorption and quick metabolism it show poor bioavailability. The present study was envisaged to investigate the possible synergistic effect of combined treatment of curcumin with piperine in suppression of diethylnitrosamine (DENA)-induced hepatocellular carcinoma (HCC) in rats, owing to permeability enhancing effect of latter. HCC was induced by supplying DENA (0.01%) in drinking water for 10 weeks. The rats were treated with curcumin (100mg/kg; p.o.) per se and curcumin along with piperine (20mg/kg; p.o.) for 4 weeks post HCC induction. The combined treatment significantly attenuated the morphological, histopathological, biochemical, apoptotic and proliferative changes in the liver and serum in comparison to curcumin per se and vehicle control group. The results of present study concluded that curcumin in combination with piperine shows better suppression of DENA-induced HCC in contrast to curcumin per se. PMID- 26278681 TI - Correction: The strength and directionality of a halogen bond are co-determined by the magnitude and size of the sigma-hole. AB - Correction for 'The strength and directionality of a halogen bond are co determined by the magnitude and size of the sigma-hole' by Michal Kolaret al., Phys. Chem. Chem. Phys., 2014, 16, 9987-9996. PMID- 26278683 TI - Age-related changes in male forearm skin-to-fat tissue dielectric constant at 300 MHz. AB - Prior research suggests that tissue dielectric constant (TDC) values are useful to assess localized skin water in females for early diagnosing breast cancer treatment-related lymphoedema and TDC values in young adults have shown gender differences. However, no TDC data are available for older males nor have ageing effects been studied despite known shifts in water state and other skin age related changes. Thus our goals were to (i) characterize TDC values at various skin depths in young and older males, (ii) determine the dependence of these values on body composition parameters and (iii) establish inter-arm TDC ratios for use as normal male reference values. TDC measurements were made to depths of 0.5, 1.5, 2.5 and 5.0 mm bilaterally on volar forearm skin in 60 males in three groups of 20 that had mean ages +/- SD of 24.0 +/- 0.9, 40.0 +/- 12.9 and 71.0 +/ 8.0 years. Total body fat and water percentages were determined via bioimpedance at 50 KHz. Results showed that (i) for all age groups TDC values decreased with increasing depth, (ii) TDC values were not statistically different among age groups except at a depth of 0.5 mm, (iii) TDC values were highly negatively correlated with total body fat and (iv) inter-arm ratios varied little among age groups and depths. It is concluded that (i) age-related larger TDC values at only the shallowest depth is consistent with skin water shifting state from bound to more mobile in the oldest group and (ii) inter-arm ratios at any depth provide a basis to test for unilateral oedema. PMID- 26278682 TI - Adolescent drinking and brain morphometry: A co-twin control analysis. AB - Developmental changes in structure and functioning are thought to make the adolescent brain particularly sensitive to the negative effects of alcohol. Although alcohol use disorders are relatively rare in adolescence, the initiation of alcohol use, including problematic use, becomes increasingly prevalent during this period. The present study examined associations between normative drinking (alcohol initiation, binge drinking, intoxication) and brain morphometry in a sample of 96 adolescent monozygotic twins. A priori regions of interest included 11 subcortical and 20 cortical structures implicated in the existing empirical literature as associated with normative alcohol use in adolescence. In addition, co-twin control analyses were used to disentangle risk for alcohol use from consequences of alcohol exposure on the developing brain. Results indicated significant associations reflecting preexisting vulnerability toward problematic alcohol use, including reduced volume of the amygdala, increased volume of the cerebellum, and reduced cortical volume and thickness in several frontal and temporal regions, including the superior and middle frontal gyri, pars triangularis, and middle and inferior temporal gyri. Results also indicated some associations consistent with a neurotoxic effect of alcohol exposure, including reduced volume of the ventral diencephalon and the middle temporal gyrus. PMID- 26278684 TI - Chiral template induced homochiral MOFs built from achiral components: SHG enhancement and enantioselective sensing of chiral alkamines by ion-exchange. AB - A pair of chiral template induced anionic homochiral frameworks constructed from achiral components has been synthesized. Ion-exchange of counter cations with polar or chiral organic cations enhances the SHG efficiency of the frameworks. The enantioselective sensing of chiral alkamines can be achieved by the SHG response. PMID- 26278685 TI - Effect of an Experimental Paste with Hydroxyapatite Nanoparticles and Fluoride on Dental Demineralisation and Remineralisation in situ. AB - This study evaluated the effect of an experimental paste containing hydroxyapatite in nanoparticles (nano-HA)/fluoride on dental de-remineralisation in situ. Thirteen subjects took part in this crossover/randomised/double-blind study performed in 4 phases (14 days each). Four sound and 4 pre-demineralised specimens were worn intraorally at each phase corresponding to the following treatments: Nanop Plus (10% HA, 0.2% NaF, nano-HA/fluoride), MI Paste Plus (casein phosphopeptide-amorphous calcium phosphate, 0.2% NaF), F (0.2% NaF) and placebo. Two-hundred and forty enamel and 240 dentine specimens were selected by using surface microhardness; half of them were subjected to pre-demineralisation and the other half remained sound. Sound specimens were further exposed to severe cariogenic challenge (20% sucrose in biofilm) in situ, while pre-demineralised specimens were not. All specimens were exposed to fluoride dentifrice slurry 2*1 min/day. Thereafter, the treatments were done for 4 min. The de-remineralisation was quantified by transversal microradiography. The data were statistically analysed by repeated-measures ANOVA/Tukey's tests (p<0.05). Generally, no huge differences were found among the treatments. However, Nanop Plus was the only treatment able to significantly reduce dentine demineralisation (x0394;Z, integrated mineral loss) and to improve enamel remineralisation (x0394;x0394;Z, integrated mineral uptake) compared to placebo. No treatments were able to reduce enamel demineralisation, while for dentine remineralisation all treatments were similarly effective in improving x0394;x0394;Z compared to placebo. Nanop Plus seems to have a positive influence on dental de-remineralisation, which should be further confirmed. PMID- 26278686 TI - Quantitative pulsed CEST-MRI using Omega-plots. AB - Chemical exchange saturation transfer (CEST) allows the indirect detection of dilute metabolites in living tissue via MRI of the tissue water signal. Selective radio frequency (RF) with amplitude B1 is used to saturate the magnetization of protons of exchanging groups, which transfer the saturation to the abundant water pool. In a clinical setup, the saturation scheme is limited to a series of short pulses to follow regulation of the specific absorption rate (SAR). Pulsed saturation is difficult to describe theoretically, thus rendering quantitative CEST a challenging task. In this study, we propose a new analytical treatment of pulsed CEST by extending a former interleaved saturation-relaxation approach. Analytical integration of the continuous wave (cw) eigenvalue as a function of the RF pulse shape leads to a formula for pulsed CEST that has the same structure as that for cw CEST, but incorporates two form factors that are determined by the pulse shape. This enables analytical Z-spectrum calculations and permits deeper insight into pulsed CEST. Furthermore, it extends Dixon's Omega-plot method to the case of pulsed saturation, yielding separately, and independently, the exchange rate and the relative proton concentration. Consequently, knowledge of the form factors allows a direct comparison of the effect of the strength and B1 dispersion of pulsed CEST experiments with the ideal case of cw saturation. The extended pulsed CEST quantification approach was verified using creatine phantoms measured on a 7 T whole-body MR tomograph, and its range of validity was assessed by simulations. PMID- 26278687 TI - Practical management of Idiopathic Pulmonary Fibrosis. AB - Idiopathic Pulmonary Fibrosis (IPF) is relentless progressive interstitial lung disease (ILD) of unknown etiology. Main pathogenesis is aberrant recovery of epithelial injury and collagen deposition. Majority of IPF patients have been elderly men with smokers. However, there are important differential diagnosis such as fibrotic non-specific interstitial pneumonia (NSIP), Connective Tissue Disease (CTD) associated ILD, chronic hypersensitivity pneumonia (CHP). Clinical point of view, non-productive cough and progressive exertional dyspnea are main symptoms. In addition, scalene muscle hypertrophy, fine crackles and finger clubbing are key findings. Serum marker such as lactate deydrogenase (LDH), Krebs von den Lungeng-6 (KL-6) are sensitive for ILD detection and activity. Pulmonary function test and 6 minute walk test (6MWT) are quite meaningful physiological examination. Serial change of forced vital capacity 6MWT distance predict mortality of IPF. International IPF guideline published recently and highlighted on the importance of high resolution computed tomography (HRCT) findings. Key findings of IPF are honeycombing, traction bronchiectasis and subpleural reticular opacity. IPF is chronic progressive disease. Therefore, tracing disease behavior is crucial and unifying clinical, physiological, imaging information over time provide useful information for physicians.In management, many candidate agent failed to have positive result. Pirfenidone which is anti-fibrotic agent showed to slow the decline of vital capacity and prevent of acute exacerbation. Molecular agent such as nintedanib is promising agent for prevention of progression of IPF. In this review, we review the clinical information of IPF and IPF guideline. Lastly, we show the clinical algorithm of this devastated disease. PMID- 26278688 TI - Serum levels of soluble CD163 as a specific marker of macrophage/monocyte activity in sarcoidosis patients. AB - BACKGROUND: Monocyte-macrophage lineage cells are the main immunocompetent cells in sarcoidosis. The main cellular elements of sarcoidal granulomas are epithelioid cells and multinucleated giant cells (MGC). MGC are also produced in vitro by human blood monocytes following various stimuli. The in vitro formation of MGC is a useful tool for understanding granulomas. CD163, a scavenger receptor for the hemoglobin-haptoglobin complex, is expressed on monocytes/macrophages and shed into blood in a soluble form (sCD163) after stimulation from Toll-like receptors and oxidative stress. sCD163 serum levels have been reported to increase in inflammatory or infectious conditions. OBJECTIVE: The aim of the present study was to examine the relationship between serum levels of sCD163 and the conventional disease markers of sarcoidosis, and also to evaluate sCD163 levels in culture supernatants following the formation of MGC by human peripheral monocytes in vitro. PATIENTS AND METHODS: Twenty sarcoidosis patients and twenty healthy subjects were enrolled in the study. sCD163 serum levels were evaluated using sCD163 ELISA. MGC were formed from peripheral blood monocytes by treatment with supernatant of concanavalin A-stimulated peripheral blood mononuclear cells, and sCD163 levels in the culture supernatants were measured by ELISA. RESULTS: sCD163 serum levels were significantly higher in sarcoidosis patients than in healthy controls and correlated with ACE and soluble interleukin-2 receptor serum levels. sCD163 levels in culture supernatants increased with the production of MGC. CONCLUSIONS: sCD163 may be used as a favorable specific marker of macrophage/monocyte activity in order to more clearly understand the disease activity of sarcoidosis. PMID- 26278689 TI - Placenta-derived mesenchymal-like cells (PDA-001) as therapy for chronic pulmonary sarcoidosis: a phase 1 study. AB - BACKGROUND: Placental derived mesenchymal-like cells have been found to have immunosuppressive effects on T cell function. We studied mesenchymal-like cells as immunomodulators in chronic pulmonary sarcoidosis. METHODS: PDA-001 cells were culture-expanded in vitro as a plastic-adherent, undifferentiated cell population that expresses the nominal phenotype CD34-, CD10+, CD105+ and CD200+. Four patients with refractory pulmonary sarcoidosis received two infusions of 150 million PDA-001 cells in 240 ml dextran-40 solution one week apart. During and for two hours after the first infusion, the pulmonary artery pressure was monitored. Prior to first infusion and within 24 hours after the second infusion, bronchoscopy and bronchoalveolar lavage (BAL) were performed. Patients underwent initial and serial pulmonary function testing and were followed for two years. RESULTS: After the first infusion, all patients had a mild, non-clinically significant increase in mean pulmonary artery pressure, but none exhibited right heart failure or volume overload. In the year following treatment, there was no significant change in the FVC, but two patients had improvement in their chest x ray and had prednisone withdrawn. BAL samples after the second infusion were sufficiently viable to undergo FACS analysis in three cases and in two patients, CD10+CD49c+C105+ cells (indicative of PDA-001 cells) were found. CONCLUSION: The use of placental derived mesenchymal-like cells led to a mild increase in pulmonary artery pressure. In some cases, these cells were found in the BAL 24 hours after the second dose. Two of four patients demonstrated some steroid sparing benefit, including one patient with prolonged remission. PMID- 26278690 TI - What comorbidities accompany sarcoidosis? A large cohort (n=1779) patients analysis. AB - BACKGROUND: Sarcoidosis is a systemic granulomatous multiorgan disease with the most common manifestation is in the chest, although the granulomas can also involve all other organs causing variety of symptoms mimicking different diseases. OBJECTIVES: To evaluate the incidence of comorbidity in a large group of patients with sarcoidosis diagnosed or followed in referral center for lung diseases in Poland. PATIENTS AND METHODS: We performed a retrospective analysis in a group of 1779 patients discharged with the final diagnosis "sarcoidosis" (ICD-10: D86) from January 2008 to October 2011. RESULTS: The majority (79.2%) were diagnosed as pulmonary and/or lymph node sarcoidosis (D86.0, D86.1, D86.2). Sarcoidosis of other and combined sites (D86.8) were diagnosed in 15.8% and unspecified (D86.9) in 5.0% of patients. At least one comorbid condition was noted in 54% of the patients, most frequently arterial hypertension (22.4%), thyroid disorders (5.6%), diabetes mellitus (5.0%), COPD (4.3%) and obesity (3.3%). Using linear regression models, the associations between the number of comorbidities and age and extent of the disease were found (p<0.001). Patients with multiorgan sarcoidosis were more likely to have a comorbid condition. CONCLUSIONS: More than half of patients with sarcoidosis have a comorbid condition, which is more likely in older patients and those with multiorgan involvement. PMID- 26278691 TI - A score for estimating survival in idiopathic pulmonary fibrosis with rest SpO2>88. AB - BACKGROUND: Prediction models for survival at baseline evaluation have been proposed in IPF but some are difficult to use. The aim of present study was to develop a new mortality risk scoring system for patients with IPF at initial evaluation. METHODS: One hundred twenty with definitive IPF were selected through a review of standardized medical records for interstitial lung diseases. Patients with resting SpO2<89% were excluded. Significant individual predictors we derived by a Cox proportional hazards model and transformed in categorical data according to cut-off points. Beta coefficients for each predictor were similar, so a score was created considering the sum of dichotomic (0 or 1) transformed variables. FINDINGS: Median follow-up time was 37.5 months. At the end of follow-up, 80 patients had died. Independent predictors of mortality by multivariate analysis included dyspnea (at rest or to light or moderate activities), FVC<70%,FEV1/FVC>0.89 and DLCO <= 40%. Resting SpO2 and ExSpO2 were excluded in final analysis. The hazard ratios ranged from 1.95 for dyspnoea to 2.30 for DLCO. When the total score was 0 (Stage I, n=28), median survival time was 68 months; when 1 or 2 (Stage II, n=69), it was 45 months; and when 3 or 4 (Stage III, n=23), it was 19 months (log rank= 60.44, p<0.001). INTERPRETATION: The score can separate IPF patients with high, intermediate and low survival. PMID- 26278692 TI - Comparison of clinical characteristics and outcomes between combined pulmonary fibrosis and emphysema associated with usual interstitial pneumonia pattern and non-usual interstitial pneumonia. AB - BACKGROUND: Recently, combined pulmonary fibrosis and emphysema (CPFE) has been recognized worldwide. However, actually CPFE had a variety of extent of emphysema or pulmonary fibrosis. OBJECTIVES: The objectives of this study were to compare the clinical characteristics and outcomes between CPFE associated with usual interstitial pneumonia pattern (UIP) and CPFE with non-UIP divided based on chest high resolution computed tomography (HRCT) images, as well as to elucidate prognostic factors. METHODS: A cohort of 57 CPFE and 64 IPF patients at a single institution was analyzed retrospectively. The HRCT imaging patterns of definite UIP pattern and possible UIP pattern were defined as UIP, and inconsistent with UIP pattern as non-UIP. Clinical characteristics and outcomes were compared in 3 subgroups with CPFE/UIP, CPFE/non-UIP, and IPF alone, respectively. The prognostic factors were performed using Cox proportional hazards. RESULTS: The incidences of primary lung cancer and acute exacerbation (AE) were 10.4%/10.9% in CPFE/UIP, 0%/27.3% in CPFE/non-UIP, and 6.3%/35.9% in IPF, respectively. The survival in CPFE/UIP had significantly worse than that in other 2 subgroups (CPFE/non-UIP, IPF) (P = 0.011, P = 0.043). The multivariate Cox regression model showed that the prognostic factors of CPFE were UIP pattern and high-composite physiologic index (CPI). CPI thresholds of 45 provided the greatest prognostic separation in patients with CPFE. CPFE/UIP with high-CPI (CPI >= 45) had a worst prognosis compared with the other groups. CONCLUSIONS: This study demonstrated that the presence of UIP pattern and high-CPI in CPFE patients were associated with poorer mortality. PMID- 26278694 TI - Estimation using the impulse oscillation system in patients with pulmonary sarcoidosis. AB - BACKGROUND: Limitations in airflow are detected in some patients with sarcoidosis in association with a poor prognosis. The impulse oscillation system (IOS) is used to treat patients with obstructive lung disease, as it can sensitively detect increased airway resistance. OBJECTIVES: To investigate the characteristics of parameters obtained with IOS in patients with sarcoidosis. METHODS: Forty-six pulmonary sarcoidosis patients at Chiba University Hospital and 20 healthy controls were enrolled. The subjects underwent IOS, pulmonary function testing and multidetector computed tomography. We evaluated the correlations between these indices in the pulmonary sarcoidosis patients and compared the pulmonary sarcoidosis patients with the healthy controls. RESULTS: The ratio of V50/V25, percentage of wall area (WA%), resistance at 5 Hz (R5) and difference between the R5 and R20 (R5-R20) values of the patients with pulmonary sarcoidosis were significantly increased compared to those observed in the controls. Inverse weak correlations were observed between the R5-R20 values and the forced expiratory volume in one second (r = -0.56; p <0.001). The R5-R20 values were correlated with the V50/V25 (r = 0.42; p < 0.005) and WA% (r = 0.43; p < 0.05) values. The WA% values were also significantly correlated with the V50/V25 (r = 0.32; p < 0.05) and R5 (r = 0.33; p < 0.05) values. CONCLUSIONS: IOS parameters were found to be significantly correlated with pulmonary function parameters and the airway wall thickness in pulmonary sarcoidosis patients. IOS is considered to be useful for detecting early manifestations of airflow limitation in pulmonary sarcoidosis patients. PMID- 26278693 TI - Cigarette smoking and male sex are independent and age concomitant risk factors for the development of ocular sarcoidosis in a New Orleans sarcoidosis population. AB - INTRODUCTION: Sarcoidosis is a multi-organ system granulomatous disease of unknown origin with an incidence of 1-40/100,000. Though pulmonary manifestations are predominant, ocular sarcoidosis (OS) affects 25-50% of patients with sarcoidosis and can lead to blindness. METHODS: A retrospective, single-center chart review of sarcoidosis cases investigated variables associated with the development of OS. Inclusion criteria were biopsy-proven sarcoidosis, disease duration greater than 1 year, documented smoking status on chart review and documentation of sarcoid-related eye disease. Multivariate analysis identified independent risk factors for OS. RESULTS: Of 269 charts reviewed, 109 patients met inclusion criteria. The OS group had a significantly higher proportion of smokers (71.4%) than without OS (42.0%, p=0.027) with no difference (p=0.61) in median number of pack years. Male sex was significantly higher in the OS group (57.1% versus 26.1%, p=0.009). Median duration of sarcoidosis was higher in the OS group (10 versus 4 years, p=0.031). Multivariate regression identified tobacco exposure (OR=5.25, p=0.007, 95% CI 1.58-17.41), male sex (OR=7.48, p=0.002, 95% CI 2.15-26.01), and age (OR=1.114, p=0.002, 95% CI 1.04-1.19) as concomitant risk factors for the development of OS. CONCLUSION: To date, there are few dedicated investigations of risk factors for OS, especially smoking. This investigation identified male sex, age, and tobacco exposure as independent risk factors for OS. Though disease duration did not withstand regression analysis in this moderately sized group, age at chart review suggests screening for OS should not remit but rather intensify in aging patients with sarcoidosis. PMID- 26278695 TI - Bone mineral density in patients with interstitial lung disease. AB - OBJECTIVE: To determine the prevalence of low bone mineral density (BMD) and the risk factors for osteoporosis in patients with interstitial lung disease (ILD). METHODS: Consecutive newly diagnosed ILD patients (n=196) were included in the study. Detailed demographic and clinical data were collected at the time of diagnosis, along with BMD measurements. Univariate and multivariate logistic regression analyses were used to determine the risk factors for osteoporosis. RESULTS: Forty-four percent of the patients had osteoporosis, and 36% had osteopenia. The diagnosis of usual interstitial pneumonia (UIP) was more frequently observed in the patients with osteoporosis than in those without osteoporosis (67 vs. 47%, respectively; p=0.005). The univariate analyses identified the following five variables that were associated with an increased risk of osteoporosis at any site: older age (odds ratios [OR], 1.06; 95% confidence intervals [CI], 1.04 - 1.09; p<0.0001), UIP diagnosis (OR, 2.39; 95% CI, 1.33 - 4.30; p=0.003), higher partial pressure of carbon dioxide (PaCO2) (OR, 1.08; 95% CI, 1.01 - 1.14; p=0.01), hypertension (OR, 1.92; 95% CI, 1.05 - 3.49; p=0.033) and diabetes mellitus (OR, 2.38; 95% CI, 1.25 - 4.56; p=0.008). However, older age was the only independent predictor of osteoporosis (adjusted OR, 1.05; 95% CI, 1.02 to 1.08; p=0.001). CONCLUSIONS: We observed a high prevalence of osteoporosis and osteopenia among newly diagnosed ILD patients. Our findings suggest that there is a substantially increased risk of osteoporosis and that early screening and aggressive treatment with various anti-bone resorptive therapies are necessary in ILD patients. PMID- 26278696 TI - Significance of granulomatous inflammation in usual interstitial pneumonia. AB - Sarcoidosis is a systemic granulomatous disease of unclear etiology with characteristic pulmonary lesions. We describe 2 unique cases of sarcoidosis where after approximately 20 years of clinical quiescence, patients developed interstitial opacities on chest CT scan and an increase in shortness of breath. With lack of therapeutic response to a course of prednisone, both patients underwent a surgical lung biopsy that revealed a pattern consistent with Usual Interstitial Pneumonia (UIP) with honeycombing and fibroblastic foci. Postoperatively, the course of the disease was consistent with what would be expected in Idiopathic Pulmonary Fibrosis. Ultimately the disease progressed with one patient needed lung transplantation and the other requiring high-flow oxygen supplementation. In conclusion, we present two patients in whom a diagnosis of sarcoidosis preceded the diagnosis of UIP by 20 years or more. The subsequent course of disease in both patients was consistent with Idiopathic Pulmonary Fibrosis. PMID- 26278697 TI - Near fatal desquamative interstitial pneumonia with bilateral recurrent tension pneumothorax. AB - Desquamative interstitial pneumonia (DIP) is an uncommon form of interstitial lung disease demonstrating good response to corticosteroid therapy and favorable prognosis. In rare cases, patients with DIP fail to respond to corticosteroid therapy, and may progress to end-stage fibrotic lung disease with respiratory failure. For such patients, well defined treatment regimen does not exist until now. We report a rare case of near fatal DIP with recurrent bilateral tension pneumothorax despite of corticosteroid maintenance therapy. Clinical and radiological findings improved with surgical intervention in addition to combination therapy with prednisolone and clarithromycin. The patient has remained in an improved state and has been receiving prednisolone and clarithromycin for 9 months. PMID- 26278698 TI - Acute eosinophilic pneumonia associated with glyphosate-surfactant exposure. AB - We report a case of a female patient who developed acute eosinophilic pneumonia (AEP) after recent onset of smoking and exposure to glyphosate-surfactant.The additional exposure associated with the recent start of smoking may have contributed to the development and/or severity of AEP.A clinical relapse after re challenge four years later both with smoking and glyphosate-surfactant made the association highly likely.Respiratory distress is a factor of poor outcome and mortality after ingestion of glyphosate-surfactant.This case highlights the importance of a thorough exposure history e.g., possible occupational and environmental exposures together with drug-intake.Genotyping should be considered in cases of severe unexplained pulmonary damage. PMID- 26278699 TI - Increased liver stiffness in idiopathic pulmonary fibrosis: a pilot study. AB - PURPOSE: There is evidence that pulmonary, hepatic and renal fibrosis may share common pathogenetic pathways. Aim of our study was to measure liver stiffness in patients affected by clinically stable idiopathic pulmonary fibrosis (IPF). METHODS: Twenty-nine cases (24 M; mean age+/-SD: 67+/-8.3 yrs; 19 ex-smokers) along with fifteen age- and sex-matched healthy volunteers were enrolled. Liver conventional ultrasound examination and transient ultrasound elastography (TUE) were realized by two independent operators. RESULTS: Mild/moderate steatosis was identified in 1 control and 8 IPF cases (6.6% and 27.5%); severe steatosis in 2 IPF patients (7%). Mean TUE measurements were increased in 11 IPF cases (38%) as compared to controls (6.4+/-2.2 kPa vs 5.2+/-0.4 kPa; p=0.02). CONCLUSIONS: To our knowledge, this is the first report suggesting that liver stiffness is increased in more than one-third of IPF patients. Application of novel methodologies should be encouraged for investigating further IPF. PMID- 26278700 TI - Seroprevalence and factors associated with seropositivity to equine arteritis virus in Spanish Purebred horses in Spain. AB - REASONS FOR PERFORMING STUDY: Equine viral arteritis (EVA), a disease caused by infection with the equine arteritis virus (EAV), is present in many European countries. In Spain, the last confirmed outbreak was reported in 1992 and there is a paucity of seroprevalence studies. The disease has a major impact on the equine breeding industry, which is mainly represented by Spanish Purebred (SP) horses in Spain. OBJECTIVES: To estimate the seroprevalence of EAV in the breeding SP horse population in central Spain and identify potential horse and studfarm level factors associated with seropositivity to EAV. STUDY DESIGN: Cross sectional study. METHODS: Individual serum samples from 555 SP horses, collected between September 2011 and November 2013 at 35 studfarms, were tested using a commercially available EAV antibody ELISA and seroneutralisation as the World Organisation for Animal Health reference confirmation test for samples with positive and equivocal results. Data on factors putatively associated with seropositivity to EAV were collected via a questionnaire and examined using random effects logistic regression for analysis of clustered data. RESULTS: Equine arteritis virus seroprevalence in the SP breeding population in central Spain standardised for the sex distribution of the reference horse population, was estimated to be 16.8% (95% confidence interval 5.2-28.5%). Increasing numbers of breeding mares on the studfarm and increasing percentage of mares with reproductive problems during the last 12 months were identified as being positively associated with EAV seropositivity. Mares vaccinated against Equine herpesvirus-1 (EHV-1) and/or -4 (EHV-4) were also positively associated with EAV seropositivity. CONCLUSIONS: These findings are of importance to ensure appropriate biosecurity measures for studfarms are carried out and may help facilitate the development of an EVA surveillance programme in the SP breeding horse population. PMID- 26278701 TI - Synthetic Biology: A New Tool for the Trade. AB - Protein-protein interactions are fundamental to many biological processes. Yet, the weak and transient noncovalent bonds that characterize most protein-protein interactions found in nature impose limits on many bioengineering experiments. Here, a new class of genetically encodable peptide-protein pairs--isopeptag N/pilin-N, isopeptag/pilin-C, and SpyTag/SpyCatcher--that interact through autocatalytic intermolecular isopeptide bond formation is described. Reactions between peptide-protein pairs are specific, robust, orthogonal, and able to proceed under most biologically relevant conditions both in vitro and in vivo. As fusion constructs, they provide a handle on molecules of interest, both organic and inorganic, that can be grasped with an iron grip. Such stable interactions provide robust post-translational control over biological processes and open new opportunities in synthetic biology for engineering programmable and self assembling protein nanoarchitectures. PMID- 26278702 TI - Clinical implications of intratumoral heterogeneity of HER2 gene amplification in locally advanced HER2-positive breast cancer patients. PMID- 26278703 TI - Protein A-Based Immunoadsorption Is More Efficient Than Conventional Plasma Exchange to Remove Circulating Anti-HLA Antibodies. AB - We retrospectively evaluated the ability of protein-A immunoadsorption (IA) as compared to that of conventional plasma exchanges (PE) in reducing the mean fluorescence intensity (MFI) of anti-HLA antibodies assessed by the single antigen assay in sensitized renal transplant recipients. Change in MFI of 441 anti-HLA antibodies was measured after 1 single session of IA or after 3 consecutive daily PE sessions. While both strategies were able to significantly lower the amount of anti-HLA antibodies, the relative reduction in MFI was higher after IA as compared to PE (-69 vs. -58%, respectively, p = 0.003). This better efficacy of IA was observed despite a lower total volume of treated plasma (105 +/- 6 vs. 160 +/- 16 ml/kg after IA and after PE, respectively). Our data suggest a higher efficiency of IA over conventional PE sessions to remove anti-HLA antibodies and call for a larger evaluation of IA to confirm its potential added value in desensitization protocols. PMID- 26278705 TI - Vasospasm Is a Consistent Finding in Pernio (Chilblains) and a Possible Clue to Pathogenesis. AB - BACKGROUND/AIMS: Pernio (chilblains) is an inflammatory condition classically characterized by localized erythema and swelling of acral sites upon exposure to cool and damp conditions. We sought to determine whether cold-induced vasospasm has a role in the development of pernio. METHODS: We retrospectively reviewed 5 patients with pernio who were seen at our institution between January 1, 2000 and December 31, 2011, and had undergone a noninvasive arterial vascular study of the upper extremities that corresponded to a site of clinical involvement of pernio and who had also undergone vasospastic testing and ice water immersion as part of the noninvasive arterial vascular study protocol. RESULTS: Vascular testing in all patients (mean age 37.8 years; 4 women) demonstrated vasospasm with ice water immersion. CONCLUSION: Our findings suggest that vasospasm likely has a role in the pathophysiology of pernio and may also provide a rationale for the pharmacological treatment of vasospasm in patients with pernio. PMID- 26278704 TI - Rocuronium: automatic infusion versus manual administration with TOF monitorisation. AB - TOF (train-of-four) monitoring provides objective data in application of neuromuscular blocking agent. Thus, applicator-based differences are eliminated and optimum muscle relaxation is maintained during operation. In the present study, we aimed to compare the effects of target-controlled infusion system and standard TOF monitoring, on use of rocuronium. ASA I-II patients, who were aged between 18 and 75 years and scheduled for elective abdominal surgery at Haydarpasa Numune Training and Research Hospital, were enrolled in the study. In order to evaluate neuromuscular blockade, the patients in Group 1 were connected to the acceleromyography device of the target-controlled infusion pump (Veryark CLMRIS-I-China) while the ones in Group 2 were connected to the routinely used acceleromyography device (TOF Watch SX). There was no significant difference between groups regarding patient characteristics, the durations of anaesthesia and surgery, quality of intubation, time to extubation and time to recovery (TOF ratio of 0.9). Intubation time was significantly longer in Group 1 (Automated group) as compared to Group 2 (Control group) (p < 0.05). The total rocuronium amount used in Group 1 was found to be significantly higher than the amount used in Group 2 (p < 0.05). There was no clinical evidence of residual neuromuscular blockage or reoccurrence of neuromuscular blockage in any patient in either group. Both methods can be used for administration of neuromuscular blocker agent during moderate time anesthesia. No advantage was noted when rocuronium was administered via automatical infusion pump during anaesthesia. PMID- 26278706 TI - Comparative Pharmacokinetics, Tissue Distribution, Excretion of Recombinant Liver Targeting Interferon with IFN alpha2b Administered Intramuscular in Rats. AB - Interferon alpha2b (IFN alpha2b) is the first cytokine, which has been approved by FDA to treat chronic hepatitis B. However, it has no organ or tissue selectivity effect, and will be rapidly cleared out in the liver after the administration treatment. In our previous study, a novel liver-targeting fusion interferon (IFN-CSP) was constructed by recombining human IFN alpha2b with a CSP region I-plus peptide. The purpose of this study is to compare pharmacokinetics, tissue distribution, excretion of recombinant liver-targeting interferon IFN-CSP with IFN alpha2b following intramuscular administration in rats and estimate whether the fusion protein recombinant liver-targeting interferon has liver targeting effect. Serum, tissue, urinary, fecal, and biliary concentrations of the drug were measured at various time points after administration using ELISA test. The pharmacokinetic character of IFN-CSP and IFNalpha2b was described using a non-compartmental model after a single intramuscular administration. Our results showed that there were no significant differences between these two drugs in pharmacokinetic and elimination. However, drug concentration of recombinant liver-targeting IFN was higher than IFN alpha2b in the liver after intramuscular administration in rats at different time points. It was increased in the spleen but not apparently, and decreased in the heart, lung and kidney. In conclusion, compared with traditional IFN alpha2b, the novel recombinant liver-targeting IFN will be more accumulated in the liver tissue. With this excellent property, IFN CSP shows a great application prospect in clinical treatment, although further investigation is still needed. PMID- 26278707 TI - The Role of Bacteria in Necrotizing Enterocolitis: Understanding the Forest for the Trees. PMID- 26278708 TI - Effects of dietary supplementation of emulsifier and carbohydrase on the growth performance, serum cholesterol and breast meat fatty acids profile of broiler chickens. AB - A total of 540 2-day-old male Ross 308 broilers were used in a 35-day experiment and were randomly divided into five treatments: (i) NC (low energy); (ii) PC (high energy diet); (iii) P1 (NC + 0.1% carbohydrases); (iv) P2 (NC + 0.05% emulsifier); and (v) P3 (NC + 0.1% carbohydrases + 0.05% emulsifier). From days 0 to 21, body weight gain in PC and P3 treatments increased (P < 0.05) compared with NC treatment. The chicks fed PC, P1, P2 and P3 improved (P < 0.05) feed conversion ratio compared with the NC treatment throughout the whole experiment. Abdominal fat weight was heavier (P < 0.05) in PC, P2 and P3 treatments than in NC and P1 treatments. On day 35, serum total cholesterol and low density lipoprotein cholesterol concentration were higher (P < 0.05) and high-density lipoprotein cholesterol was lower (P < 0.05) in NC and P2 treatments than in PC, P1 and P3 treatments. The concentration of oleic acid, linoleic acid and total unsaturated fatty acids were highest (P < 0.05) in PC than in the other treatments. In conclusion, the results indicate that low energy density diet had lower growth performance, while the inclusion of emulsifier and carbohydrases in low energy diets can partially improve growth performance. PMID- 26278709 TI - Worsening of respiratory status during neutropenia recovery in noncritically ill hematological patients: results of a prospective multicenter study. AB - BACKGROUND: Neutropenia recovery (NR) has been associated with worsening preexisting lung injury in up to 50% of critically ill cancer patients. However, only limited relevant data exist in the general population of hematological patients. OBJECTIVES: To assess the incidence of acute respiratory deterioration during NR in patients with hematological malignancies. METHODS: Adult patients with neutropenia expected to last more than 7 days were included. Worsening of respiratory status (WRS) was defined as a decrease in oxygen saturation of >=5%, the need for oxygen therapy for >=24 h, an increase in oxygen flow of >=50% in patients previously treated with oxygen, or the need for mechanical ventilation. NR was defined as the 3 days preceding or following a neutrophil count of >0.5 * 109/l. RESULTS: A total of 16 of 50 patients included in this pilot study experienced WRS during NR (32%), and 13 patients had WRS during neutropenia (26%). The incidence density of WRS was 0.53 (+/-0.79) episodes per 10 days during NR and 0.20 (+/-0.39) episodes per 10 days during neutropenia (p = 0.004). Sepsis, stem cell transplantation, preexisting pneumonia, or the use of granulocyte colony-stimulating factor were not associated with WRS during NR. CONCLUSION: Up to one third of noncritically ill hematological patients with expected neutropenia of more than 7 days experience WRS during NR. Clinical consequences and risk factors for WRS during NR remain to be evaluated. PMID- 26278710 TI - A European curriculum for nurses working in haemophilia. AB - INTRODUCTION: Currently, there is no consensus on education required to develop haemophilia nursing. The aim was to develop a curriculum for haemophilia nurses that could be used as a resource in Europe. This could form a basis for continuous professional development and used in the preparation of specialized educational programmes. METHODS: The EAHAD nurses working group set out to describe the skills and knowledge needed for a nurse to work in this specialty. This was considered at two levels: basic requirements and at a more advanced level. The working group acted as a focus group for this project drawing on existing specialist training, national role definitions, competencies and results of the EAHAD Nurses survey (2012). A template was populated with the knowledge base and the skills required. RESULTS: Themes were analysed and information generated organized into domains: content of curriculum; learning outcomes, defined in terms of knowledge, skills, behaviour and attitudes; and suggestions for teaching methods. For curriculum content the following domains were identified: Applied biological science; treatment and management of haemophilia and associated disorders; genetic practice; care management of affected carriers and women; the impact of living with bleeding disorders; evidence base and applied research in haemophilia practice; and, the specialist role of the haemophilia nurse. Examples are given for teaching and learning process. CONCLUSION: This curriculum is intended for use as a strategic resource to outline education for the haemophilia nurse and contribute to the standardization and benchmarking of haemophilia nursing care and thus to improvement in the quality of patient care. PMID- 26278711 TI - Signal transduction in Acute Myeloid Leukemia - Implications for Novel Therapeutic Concepts. AB - Acute Myeloid Leukemia (AML) is a highly aggressive clonal hematopoietic disorder that has been managed with largely unchanged treatment protocols for the past decades. Although conventional chemotherapy bears the potential to cure some AML patients, the course of the disease is frequently fatal despite treatment highlighting the need for novel therapeutic concepts. Recent progress in genetic technologies significantly furthered our understanding of the molecular events leading to the disease, but these advances have not yet been successfully translated into improved treatment outcomes. Here, we review some of the new promising targets expressed by leukemic blasts, including important signaling pathways involved in AML stem/progenitor cell maintenance and drug resistance. We furthermore discuss novel targeted therapies in pre-clinical and clinical development thereby focusing on new compounds targeting receptor and non-receptor tyrosine kinases, farnesyltransferase proteins, and epigenetic modifiers. PMID- 26278712 TI - Nab-Paclitaxel in Metastatic Breast Cancer: Defining the Best Patient Profile. AB - Around 40% of patients with breast cancer will present with a recurrence of the disease. Chemotherapy is recommended for patients with recurrent hormone independent or hormone-refractory breast cancer and almost all patients with metastatic breast cancer (MBC) receive chemotherapy during their medical history. Nanoparticle albuminbound (nab)-paclitaxel is a solvent-free, 130-nanometer particle formulation of paclitaxel. Nab-paclitaxel can be administered to all patients for whom the treatment choice is a taxane. In this review, 6 patient profiles for which nabpaclitaxel may be particularly useful are described and analyzed: (i) as first-line treatment of MBC, (ii) as second-line treatment of MBC after oral chemotherapy, (iii) after a standard taxane, (iv) as third-line treatment after a standard taxane and oral chemotherapy, (v) for patients with HER2-positive MBC and (vi) for patients with intolerance to standard taxanes. Nab paclitaxel is a rational treatment choice for patients with MBC in different settings, as well as for those with prior exposure to a standard taxane. PMID- 26278714 TI - Epigallocatechin-3-gallate Increases RXRgamma-mediated Pro-apoptotic and Anti invasive Effects in Gastrointestinal Cancer Cell Lines. AB - Molecules with synergistic effects often enhance the benefits of cancer therapy. We observed that the major catechin of green tea, (-)-Epigallocatechin-3-gallate (EGCG), induced retinoid X receptor-gamma (RXRgamma) expression in the SK-Ch-A1 cholangiocarcinoma cell line and in two colon carcinoma cell lines (LoVo and the derivative multi-drug resistant LoVoMDR). On this basis, we analyzed the effects of EGCG in combination with an RXRgamma ligand, 6-OH-11-O-hydroxyphenantrene (IIF), or with a ligand of retinoic acid receptor, all-trans-retinoic acid (RA). IIF alone and in combination with EGCG activated the retinoic X response elements and induced the germ cell nuclear factor. In parallel, EGCG induced 67 kDa laminin receptor expression alone and in combination with IIF. We observed a synergistic growth inhibition with EGCG and IIF in combination at lower doses. These effects were accompanied by apoptosis activation through the mitochondrial pathway. Moreover, in LoVo cell line we observed an induction of Forkhead box O3 expression, another molecule involved in apoptosis activation. Finally, metalloproteinase activity and extracellular matrix metalloproteinase inducer (EMMPRIN) expression were inhibited and tumor cell invasion was strongly reduced in the SK-Ch-A1 cell line after treatment with EGCG and IIF. In conclusion, the use of specific RXR ligands in combination with catechins could open a new perspective in gastrointestinal tumor chemoprevention. PMID- 26278713 TI - Old Tyrosine Kinase Inhibitors and Newcomers in Gastrointestinal Cancer Treatment. AB - Gastrointestinal cancer treatment is based more on molecular biology that has provided increasing knowledge about cancer pathogenesis on which targeted therapy is being developed. Precisely, targeted therapy is defined as a "type of treatment that uses drugs, such as monoclonal antibodies or tyrosine kinase inhibitors, to identify and attack specific cancer cells". Nowadays, the United States Food and Drug Administration has approved many targeted therapies for gastrointestinal cancer treatment, as many are in various phases of development as well. In a previous review we discussed the main monoclonal antibodies used and studied in gastrointestinal cancer. In addition to monoclonal antibodies, tyrosine kinase inhibitors represent another class of targeted therapy and following the approval of imatinib for gastrointestinal stromal tumours, other tyrosine kinase inhibitors have been approved for gastrointestinal cancers treatment such as sunitinib, regoragenib, sorafenib and erlotinib. Moving forward, the purpose of this review is to focus on the efficacy data of main tyrosine kinase inhibitors commonly used in the personalized treatment of each gastrointestinal tumour and to provide a comprehensive overview about experimental targeted therapies ongoing in this setting. PMID- 26278716 TI - Pemphigoid Diseases as a Sign of Active Psoriasis: A Case Report and Brief Review. AB - BACKGROUND: Overlap of bullous pemphigoid (BP) with chronic psoriatic plaques (CPP) is a common condition. However, the association of BP with pustular psoriasis (PP) is uncommon. Moreover, perilesional erythema and pustular lesions on CPP are accepted as a sign of unstable psoriasis. Unstable psoriasis could be triggered by certain irritant topical treatments against psoriasis. These chemical agents could also induce a localized pattern of generalized PP. Here, we describe BP and PP collision in unstable CPP. OBJECTIVE: By this observation we suggest that BP could be a sign of active psoriasis. Presumably, psoriasis induced BP is an inflammation activity-dependent condition. METHODS: This study is a case report and literature review. RESULTS: The dramatic response of bullo pustular lesions to short-term methotrexate (MTX) treatment suggests the rule of 'no psoriasis, no BP'. Presumably, MTX supressed the active inflammation of CPP and BP disappeared following CPP control. CONCLUSION: BP can be a sign of active psoriasis in the present case. PMID- 26278717 TI - Role for HIF-1alpha and Downstream Pathways in Regulating Neuronal Injury after Intracerebral Hemorrhage in Diabetes. AB - BACKGROUND/AIMS: HIF-1alpha is accumulated in the cellular nucleus and cytoplasm under conditions of oxygen deprivation and engaged in pathophysiologic changes of homeostasis by modulating the expression of several target genes. As an endogenous signaling protein, HIF-1alpha contributes to in neuroprotection, erythropoiesis, and apoptosis modulation. The purpose of this study was to examine the role played by HIF-1alpha in regulating neurological injury evoked by intracerebral hemorrhage (ICH) through its downstream product, namely vascular endothelial growth factor (VEGF). In particular, we examined the effects of diabetic hyperglycemia on HIF-1alpha response in the processing of ICH. METHODS: ELISA was used to measure HIF-1alpha and VEGF; and Western Blot analysis to examine the protein expression of VEGFR-2 and Caspase-3. Neurological Severity Score and brain water content were used to indicate neurological function and brain edema. RESULTS: HIF-1alpha and VEGF were significantly increased in the brain after induction of ICH in non-diabetic control rats and diabetic rats; however, the amplified levels of HIF-1alpha and VEGF were attenuated in diabetic rats (P<0.05 vs. non-diabetic rats) as compared with non-diabetic rats. Also, the protein expression of VEGF receptor subtype 2 was significantly less in the brain of diabetic rats (P<0.05 vs. non-diabetic rats). Further, cerebral infusion of HIF-1 activator stabilized VEGF levels, attenuated Caspase-3 and improved neurological deficits induced by ICH and the effects are smaller in diabetic animals. CONCLUSION: HIF-1alpha activated by ICH likely plays a beneficial role via VEGF mechanisms and response of HIF-1alpha is largely impaired in diabetes. This has pharmacological implications to target specific HIF-1alpha and VEGF pathway for neuronal dysfunction and vulnerability related to ICH. PMID- 26278718 TI - 22q11.21 Deletion Syndromes: A Review of Proximal, Central, and Distal Deletions and Their Associated Features. AB - Chromosome 22q11.21 contains a cluster of low-copy repeats (LCRs), referred to as LCR22A-H, that mediate meiotic non-allelic homologous recombination, resulting in either deletion or duplication of various intervals in the region. The deletion of the DiGeorge/velocardiofacial syndrome interval LCR22A-D is the most common recurrent microdeletion in humans, with an estimated incidence of ~1:4,000 births. Deletion of other intervals in 22q11.21 have also been described, but the literature is often confusing, as the terms 'proximal', 'nested', 'distal', and 'atypical' have all been used to describe various of the other intervals. Individuals with deletions tend to have features with widely variable expressivity, even among families. This review concisely delineates each interval and classifies the reported literature accordingly. PMID- 26278719 TI - Serum S100A12: A Risk Marker or Risk Factor of Vascular Calcification in Chronic Kidney Disease. PMID- 26278720 TI - [Not Available]. PMID- 26278721 TI - [Not Available]. PMID- 26278722 TI - Paper Records of Patients in Isolation for Colonization or Infection With Special Organisms: A Potential Fomite? PMID- 26278723 TI - Effects of CO2 Pneumoperitoneum on the Cognitive Function of Patients Undergoing Gynecologic Laparoscopy. AB - AIM: To evaluate the effects of CO2 pneumoperitoneum during gynecologic laparoscopy on patients' postoperative cognitive function. METHODS: This prospective clinical study included 225 adult female patients with American Society of Anesthesiologists physical status I or II. Patients underwent conventional open surgery (group I, n = 115) or gynecologic laparoscopy using abdominal insufflation with CO2 to an intra-abdominal pressure of 15 mm Hg (group II, n = 110). Serum S100beta and neuron-specific enolase (NSE) concentrations were measured, both immediately before surgery and before the patient awoke after surgery. The Mini-Mental State Examination (MMSE) was administered 1 day before surgery as well as 1, 6, 12, 24 and 72 h after surgery and before discharge. RESULTS: MMSE scores were significantly lower relative to baseline at 1, 6 and 12 h post surgery, but returned to baseline by 48 h (group I) or 72 h (group II) post surgery. One hour after surgery, S100beta serum levels were higher in group II than in group I (p < 0.05). NSE levels did not differ between the groups. In group II, the MMSE score significantly correlated with serum S100beta or NSE concentrations. CONCLUSION: CO2 pneumoperitoneum influences postoperative cognitive function in patients undergoing gynecologic laparoscopy. PMID- 26278725 TI - Terminating observation within matched pairs of subjects in a matched cohort analysis: a Monte Carlo simulation study. AB - Matched cohort analyses are becoming increasingly popular for estimating treatment effects in observational studies. However, in the applied biomedical literature, analysts and authors are inconsistent regarding whether to terminate follow-up among members of a matched set once one member is no longer under observation. This paper focused on time-to-event outcomes and used Monte Carlo simulation methods to determine the optimal approach. We found that the bias of the estimated treatment effect estimate was negligible under both approaches and that the percentage of censoring had no discernible effect on the magnitude of bias. The mean model-based standard error of the treatment estimate was consistently higher when we terminated observation within matched pairs. Furthermore, the type 1 error rate was consistently lower when we did not terminate follow-up within matched pairs. In conclusion, when the focus was on time-to-event outcomes, we demonstrated that there was no advantage to terminating follow-up within matched pairs. Continuing follow-up on each subject until their observation was naturally complete was superior compared with terminating a subject's observation time once its matched pair had ceased to be under observation. Given the frequency with which these analyses are conducted in the applied literature, our results provide important guidance to analysts and applied researchers as to the preferred analytic approach. PMID- 26278724 TI - On the front line of HIV virological monitoring: barriers and facilitators from a provider perspective in resource-limited settings. AB - Scale-up of viral load (VL) monitoring for HIV-infected patients on antiretroviral therapy (ART) is a priority in many resource-limited settings, and ART providers are critical to effective program implementation. We explored provider-perceived barriers and facilitators of VL monitoring. We interviewed all providers (n = 17) engaged in a public health evaluation of dried blood spots for VL monitoring at five ART clinics in Malawi. All ART clinics were housed within district hospitals. We grouped themes at patient, provider, facility, system, and policy levels. Providers emphasized their desire for improved ART monitoring strategies, and frustration in response to restrictive policies for determining which patients were eligible to receive VL monitoring. Although many providers pled for expansion of monitoring to include all persons on ART, regardless of time on ART, the most salient provider-perceived barrier to VL monitoring implementation was the pressure of work associated with monitoring activities. The work burden was exacerbated by inefficient data management systems, highlighting a critical interaction between provider-, facility-, and system level factors. Lack of integration between laboratory and clinical systems complicated the process for alerting providers when results were available, and these communication gaps were intensified by poor facility connectivity. Centralized second-line ART distribution was also noted as a barrier: providers reported that the time and expenses required for patients to collect second-line ART frequently obstructed referral. However, provider empowerment emerged as an unexpected facilitator of VL monitoring. For many providers, this was the first time they used an objective marker of ART response to guide clinical management. Providers' knowledge of a patient's virological status increased confidence in adherence counseling and clinical decision-making. Results from our study provide unique insight into provider perceptions of VL monitoring and indicate the importance of policies responsive to individual and environmental challenges of VL monitoring program implementation. Findings may inform scale-up by helping policy-makers identify strategies to improve feasibility and sustainability of VL monitoring. PMID- 26278726 TI - Synthesis of Ultrathin and Thickness-Controlled Cu2-xSe Nanosheets via Cation Exchange. AB - We demonstrate the use of cation exchange to synthesize ultrathin and thickness controlled Cu2-xSe nanosheets (NSs) beginning with CdSe NSs. In this manner, extremely thin (i.e., 1.6 nm thickness) Cu2-xSe NSs, beyond which can be made directly, have been obtained. Furthermore, they represent the thinnest NSs produced via cation exchange. Notably, the exchange reaction preserves the starting morphology of the CdSe sheets and also retains their cubic crystal structure. The resulting nonstoichiometric and cubic Cu2-xSe NSs are stable and do not exhibit any signs of Cu or Se oxidation after exposure to air for 2 weeks. Resulting NSs also show the existence of a localized surface plasmon resonance in the infrared due to the presence of copper vacancies. Efforts to isolate intermediates during the cation exchange reaction show that it occurs via a mechanism where entire sheets are rapidly converted into the final product once the exchange reaction commences, precluding the isolation of alloyed species. PMID- 26278727 TI - Large-Scale Density Functional Theory Transition State Searching in Enzymes. AB - Linear-scaling quantum mechanical density functional theory calculations have been applied to study the rearrangement of chorismate to prephenate in large scale models of the Bacillus subtilis chorismate mutase enzyme. By treating up to 2000 atoms at a consistent quantum mechanical level of theory, we obtain an unbiased, almost parameter-free description of the transition state geometry and energetics. The activation energy barrier is calculated to be lowered by 10.5 kcal mol(-1) in the enzyme, compared with the equivalent reaction in water, which is in good agreement with experiment. Natural bond orbital analysis identifies a number of active site residues that are important for transition state stabilization in chorismate mutase. This benchmark study demonstrates that linear scaling density functional theory techniques are capable of simulating entire enzymes at the ab initio quantum mechanical level of accuracy. PMID- 26278728 TI - Complete Quantum State Selectivity in Cold Molecular Beams Using Deflection Resistant Dark States in a STIRAP Configuration. AB - One of the main goals of chemical dynamics is the creation of molecular beams composed of a single (vibrational, rotational, and magnetic) quantum state of choice. In this Letter, we propose a method to achieve complete quantum state selectivity by producing resistance to electromagnetically induced deflection (EID) and that the state to be selected can be "dialed in" at will. We illustrate the method by showing in detail how to purify thermal beams of the LiRb and IF molecules to yield molecular beams composed of a variety of prechosen single internal quantum states and/or superpositions of such states. We expect that this method will be implemented in all subsequent explorations of the fundamentals of chemical reactions and their control and the use of cold molecules as a vehicle for studying some of the most profound issues of quantum dynamics. PMID- 26278729 TI - Anomalous Alloy Properties in Mixed Halide Perovskites. AB - Engineering halide perovskite through mixing halogen elements, such as CH3NH3PbI3 xClx and CH3NH3PbI3-xBrx, is a viable way to tune its electronic and optical properties. Despite many emerging experiments on mixed halide perovskites, the basic electronic and structural properties of the alloys have not been understood and some crucial questions remain, for example, how much Cl can be incorporated into CH3NH3PbI3 is still unclear. In this Letter, we chose CsPbX3 (X = I, Br, Cl) as an example and use a first-principle calculation together with cluster expansion methods to systematically study the structural, electronic, and optical properties of mixed halide perovskites and find that unlike conventional semiconductor alloys, they exhibit many anomalous alloy properties such as small or even negative formation energies at some concentrations and negligible or even negative band gap bowing parameters at high temperature. We further show that mixed-(I,Cl) perovskite is hard to form at temperature below 625 K, whereas forming mixed-(Br,Cl) and (I,Br) alloys are easy at room temperature. PMID- 26278730 TI - Spectroscopic Study of Anisotropic Excitons in Single Crystal Hexacene. AB - The linear optical response of hexacene single crystals over a spectral range of 1.3-1.9 eV was studied using polarization-resolved reflectance spectroscopy at cryogenic temperatures. We observe strong polarization anisotropy for all optical transitions. Pronounced deviations from the single-molecule, solution-phase spectra are present, with a measured Davydov splitting of 180 meV, indicating strong intermolecular coupling. The energies and oscillator strengths of the relevant optical transitions and polarization-dependent absorption coefficients are extracted from quantitative analysis of the data. PMID- 26278731 TI - Optical Properties of Triangular Molybdenum Disulfide Nanoflakes. AB - The results from calculations of optical and electronic properties of triangular MoS2 nanoflakes with edge lengths ranging from 1.6 to 10.4 nm are presented. The optical spectra were calculated using the time-dependent extension of the density functional tight-binding method (TD-DFTB). The size effect in the optical absorption spectra is clearly visible. With decreasing length of the nanoflakes edges, the long-wavelength absorption in the range of visible light is shifted toward short-wavelength absorption, confirming a quantum-confinement-like behavior of these flakes. In contrast, the edges of the nanoflakes exhibit a distinct metallic-like behavior. The relation of the absorption properties to the observed photoluminescence of MoS2 nanoflakes is discussed in a qualitative manner. PMID- 26278732 TI - A Signature of Roaming Dynamics in the Thermal Decomposition of Ethyl Nitrite: Chirped-Pulse Rotational Spectroscopy and Kinetic Modeling. AB - Chirped-pulse (CP) Fourier transform rotational spectroscopy is uniquely suited for near-universal quantitative detection and structural characterization of mixtures that contain multiple molecular and radical species. In this work, we employ CP spectroscopy to measure product branching and extract information about the reaction mechanism, guided by kinetic modeling. Pyrolysis of ethyl nitrite, CH3CH2ONO, is studied in a Chen type flash pyrolysis reactor at temperatures of 1000-1800 K. The branching between HNO, CH2O, and CH3CHO products is measured and compared to the kinetic models generated by the Reaction Mechanism Generator software. We find that roaming CH3CH2ONO -> CH3CHO + HNO plays an important role in the thermal decomposition of ethyl nitrite, with its rate, at 1000 K, comparable to that of the radical elimination channel CH3CH2ONO -> CH3CH2O + NO. HNO is a signature of roaming in this system. PMID- 26278733 TI - Computational and Experimental Investigation of Ti Substitution in Li1(NixMnxCo1 2x-yTiy)O2 for Lithium Ion Batteries. AB - Aliovalent substitutions in layered transition-metal cathode materials has been demonstrated to improve the energy densities of lithium ion batteries, with the mechanisms underlying such effects incompletely understood. Performance enhancement associated with Ti substitution of Co in the cathode material Li1(NixMnxCo1-2x)O2 were investigated using density functional theory calculations, including Hubbard-U corrections. An examination of the structural and electronic modifications revealed that Ti substitution reduces the structural distortions occurring during delithiation due to the larger cation radius of Ti(4+) relative to Co(3+) and the presence of an electron polaron on Mn cations induced by aliovalent Ti substitution. The structural differences were found to correlate with a decrease in the lithium intercalation voltage at lower lithium concentrations, which is consistent with quasi-equilibrium voltages obtained by integrating data from stepped potential experiments. Further, Ti is found to suppress the formation of a secondary rock salt phase at high voltage. Our results provide insights into how selective substitutions can enhance the performance of cathodes, maximizing the energy density and lifetime of current Li ion batteries. PMID- 26278734 TI - Ultrafast Terahertz Photoconductivity of Photovoltaic Polymer-Fullerene Blends: A Comparative Study Correlated with Photovoltaic Device Performance. AB - Ultrafast photoinduced carrier dynamics in prototypical low band gap polymer:fullerene photovoltaic blend films PTB7:PC70BM and P3HT:PC70BM is investigated using ultrafast terahertz (THz) spectroscopy. The subpicosecond and few-picosecond decays of THz-probed photoconductivities for both compounds are observed, attributed to the rapid formation of polaron pairs by exciton-exciton annihilation and subsequent polaron pair annihilation, respectively. The transient THz photoconductivity spectra of PTB7:PC70BM are well described by the Drude-Smith (DS) model, directly yielding the important charge transport parameters such as charge carrier density, momentum scattering time, and effective localization. By comparison with P3HT:PC70BM, we find that in PTB7:PC70BM the mobile charge carrier photoconductivity is significantly enhanced by a factor of 1.8 and prevails for longer times after charge formation, due to both improved mobile charge carrier yield and lower charge localization. In PTB7:PC70BM, a strong dependency of electron momentum scattering time on electron density was found, well parametrized by the empirical Caughey-Thomas model. The difference in ultrafast photoconductivities of both P3HT:PC70BM and PTB7:PC70BM is found to correlate very well with the performance of photovoltaic devices based on those materials. PMID- 26278735 TI - Correlating Non-Geminate Recombination with Film Structure: A Comparison of Polythiophene: Fullerene Bilayer and Blend Films. AB - The morphology of the active layer in polymer:fullerene solar cells is a key parameter in determining their performance. In this study we monitor the charge carrier dynamics in bilayers of poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl C61-butyric acid methyl ester (PCBM) (fabricated by sequential spin coating and vacuum deposition) before and after thermal annealing, and compare these against conventional solution processed bulk heterojunction (BHJ) blend films. Transmission electron microscopy images, supported by field effect mobility data show that while not-annealed P3HT/PC61BM bilayers possess a sharp interface, intermixing proceeds upon annealing. Transient absorption studies indicate that the not-annealed bilayer yields fewer, but longer lived, charge carriers compared to the BHJ. Monte Carlo (MC) simulations further suggest that the difference in non-geminate recombination dynamics observed for the BHJ and bilayer films could be related to the confinement of charge carriers to the interface, with the lower dimensionality for the flat interface bilayer films relative to the intercalated donor-acceptor network BHJ films leading to lower recombination. PMID- 26278736 TI - Exploring Strategies for High Dielectric Constant and Low Loss Polymer Dielectrics. AB - Polymer dielectrics having high dielectric constant, high temperature capability, and low loss are attractive for a broad range of applications such as film capacitors, gate dielectrics, artificial muscles, and electrocaloric cooling. Unfortunately, it is generally observed that higher polarization or dielectric constant tends to cause significantly enhanced dielectric loss. It is therefore highly desired that the fundamental physics of all types of polarization and loss mechanisms be thoroughly understood for dielectric polymers. In this Perspective, we intend to explore advantages and disadvantages for different types of polarization. Among a number of approaches, dipolar polarization is promising for high dielectric constant and low loss polymer dielectrics, if the dipolar relaxation peak can be pushed to above the gigahertz range. In particular, dipolar glass, paraelectric, and relaxor ferroelectric polymers are discussed for the dipolar polarization approach. PMID- 26278737 TI - The Strongest Particle: Size-Dependent Elastic Strength and Debye Temperature of PbS Nanocrystals. AB - We investigated the elastic compressibility of PbS nanocrystals (NCs) pressurized in a diamond anvil cell and simultaneously probed the structure using synchrotron based X-ray diffraction. The compressibility of PbS NCs exhibits bimodal size dependence. The elastic modulus of small NCs increases with increasing diameter and peaks near a particle diameter of approximately 7 nm. For large NCs the elastic modulus decreases toward the bulk value with increasing NC diameter. We explain the bimodal size-dependence of the elastic modulus in terms of a core shell model based on distinct elasticity of the crystal near the surface and in the core of the particle. We combined insights into the size-dependent elasticity and lattice spacing to determine the Debye temperature of PbS NCs as a function of particle diameter. Understanding the size-dependent elasticity of defect-free colloidal NCs provides new insights into their crystal structure and mechanical properties. PMID- 26278738 TI - Rational Codoping as a Strategy to Improve Optical Properties of Doped Semiconductor Quantum Dots. AB - Doping is a powerful and convenient technique for rationally altering the electronic, magnetic, and optical properties of materials including nanomaterials such as quantum dots (QDs) or nanocrystals (NCs). Most doping involves introduction of an impurity element or ion, into the crystal lattice of the host material, which tends to result in lattice distortion and/or charge imbalance when the dopant charge does not match the charge of the host ion replaced. One solution to such problems is codoping with another element or ion that helps to reduce lattice distortion or charge imbalance, which can stabilize the primary dopant in the host lattice and substantially improve the photoluminescence (PL) of the primary dopant. Furthermore, interaction between the codopant and primary dopant can be used to tune the PL properties by altering energy levels related to donor-acceptor pair recombination. PMID- 26278739 TI - Spatial Mapping of Sub-Bandgap States Induced by Local Nonstoichiometry in Individual Lead Sulfide Nanocrystals. AB - The properties of photovoltaic devices based on colloidal nanocrystals are strongly affected by localized sub-bandgap states associated with surface imperfections. A correlation between their properties and the atomic-scale structure of chemical imperfections responsible for their appearance must be established to understand the nature of such surface states. Scanning tunneling spectroscopy is used to visualize the manifold of electronic states in annealed ligand-free lead sulfide nanocrystals supported on the Au(111) surface. Delocalized quantum-confined states and localized sub-bandgap states are identified, for the first time, via spatial mapping. Maps of the sub-bandgap states show localization on nonstoichiometric adatoms self-assembled on the nanocrystal surfaces. The present model study sheds light onto the mechanisms of surface state formation that, in a modified form, may be relevant to the more general case of ligand-passivated nanocrystals, where under-coordinated surface atoms exist due to the steric hindrance between passivating ligands attached to the nanocrystal surface. PMID- 26278740 TI - Quantum Nonlinear Optics with Polar J-Aggregates in Microcavities. AB - We predict that an ensemble of organic dye molecules with permanent electric dipole moments embedded in a microcavity can lead to strong optical nonlinearities at the single-photon level. The strong long-range electrostatic interaction between chromophores due to their permanent dipoles introduces the desired nonlinearity of the light-matter coupling in the microcavity. We develop a semiclassical model to obtain the absorption spectra of a weak probe field under the influence of strong exciton-photon coupling with the cavity field. Using realistic parameters, we demonstrate that a cavity field with an average photon number near unity can significantly modify the absorptive and dispersive response of the medium to a weak probe field at a different frequency. Finally, we show that the system is in the regime of cavity-induced transparency with a broad transparency window for dye dimers. We illustrate our findings using pseudoisocyanine chloride (PIC) J-aggregates in currently available optical microcavities. PMID- 26278741 TI - Defining the Proton Topology of the Zr6-Based Metal-Organic Framework NU-1000. AB - Metal-organic frameworks (MOFs) constructed from Zr6-based nodes have recently received considerable attention given their exceptional thermal, chemical, and mechanical stability. Because of this, the structural diversity of Zr6-based MOFs has expanded considerably and in turn given rise to difficulty in their precise characterization. In particular it has been difficult to assign where protons (needed for charge balance) reside on some Zr6-based nodes. Elucidating the precise proton topologies in Zr6-based MOFs will have wide ranging implications in defining their chemical reactivity, acid/base characteristics, conductivity, and chemical catalysis. Here we have used a combined quantum mechanical and experimental approach to elucidate the precise proton topology of the Zr6-based framework NU-1000. Our data indicate that a mixed node topology, [Zr6(MU3-O)4(MU3 OH)4(OH)4 (OH2)4](8+), is preferred and simultaneously rule out five alternative node topologies. PMID- 26278742 TI - Nanotubes from Misfit Layered Compounds: A New Family of Materials with Low Dimensionality. AB - Nanotubes that are formed from layered materials have emerged to be exciting one dimensional materials in the last two decades due to their remarkable structures and properties. Misfit layered compounds (MLC) can be produced from alternating assemblies of two different molecular slabs with different periodicities with the general formula [(MX)1+x]m[TX2]n (or more simply MS-TS2), where M is Sn, Pb, Bi, Sb, rare earths, T is Sn, Nb, Ta, Ti, V, Cr, and so on, and X is S, Se. The presence of misfit stresses between adjacent layers in MLC provides a driving force for curling of the layers that acts in addition to the elimination of dangling bonds. The combination of these two independent forces leads to the synthesis of misfit layered nanotubes, which are newcomers to the broad field of one-dimensional nanostructures and nanotubes. The synthesis, characterization, and microscopic details of misfit layered nanotubes are discussed, and directions for future research are presented. PMID- 26278743 TI - Quantifying Surfactant Alkyl Chain Orientation and Conformational Order from Sum Frequency Generation Spectra of CH Modes at the Surfactant-Water Interface. AB - We combine second-order nonlinear vibrational spectroscopy and quantum-chemical calculations to quantify the molecular tilt angle and the structural variation of a decanoic acid surfactant monolayer on water. We demonstrate that there is a remarkable degree of delocalization of the vibrational modes along the backbone of the amphiphilic molecule. A simulation-based on modeled sum frequency generation (SFG) spectra offers quantitative insights into the disorder of surfactant monolayers at the water-air interface. It is shown that an average of one gauche defect in the alkyl chain suffices to give rise to the methylene stretch intensity similar in magnitude to the methyl stretch. PMID- 26278744 TI - Experimental Measurement of the Binding Configuration and Coverage of Chirality Sorting Polyfluorenes on Carbon Nanotubes. AB - Poly(9,9-dioctylfluorene-2,7-diyl) (PFO) exhibits exceptional (n,m) chirality and electronic-type selectivity for near-armchair semiconducting carbon nanotubes. To better understand and control the factors governing this behavior, we experimentally determine the surface coverage and binding configuration of PFO on nanotubes in solution using photoluminescence energy transfer and anisotropy measurements. The coverage increases with PFO concentration in solution, following Langmuir-isotherm adsorption behavior with cooperativity. The equilibrium binding constant (PFO concentration in solution at half coverage), KA, depends on (n,m) and is 1.16 +/- 0.30, 0.93 +/- 0.12, and 1.13 +/- 0.26 mg mL(-1) for the highly selected (7,5), (8,6), and (8,7) species, respectively, and the corresponding PFO wrapping angle at low coverage is 12, 17, and 14 +/- 2 degrees , respectively. In contrast, the inferred KA for metallic nanotubes is nearly an order of magnitude greater, indicating that the semiconducting selectivity increases with decreasing PFO concentration. This understanding will quantitatively guide future experimental and computational efforts on electronic type-sorting carbon nanotubes. PMID- 26278745 TI - Analyzing Structural Changes of Fe-N-C Cathode Catalysts in PEM Fuel Cell by Mobetabauer Spectroscopy of Complete Membrane Electrode Assemblies. AB - The applicability of analyzing by Mobetabauer spectroscopy the structural changes of Fe-N-C catalysts that have been tested at the cathode of membrane electrode assemblies in proton exchange membrane (PEM) fuel cells is demonstrated. The Mobetabauer characterization of powders of the same catalysts was recently described in our previous publication. A possible change of the iron species upon testing in fuel cell was investigated here by Mobetabauer spectroscopy, energy dispersive X-ray cross-sectional imaging, and neutron activation analysis. Our results show that the absorption probability of gamma rays by the iron nuclei in Fe-N-C is strongly affected by the presence of Nafion and water content. A detailed investigation of the effect of an oxidizing treatment (1.2 V) of the non noble cathode in PEM fuel cell indicates that the observed activity decay is mainly attributable to carbon oxidation causing a leaching of active iron sites hosted in the carbon matrix. PMID- 26278746 TI - Isolation and Tandem Mass Spectrometric Identification of a Stable Monolayer Protected Silver-Palladium Alloy Cluster. AB - A selenolate-protected Ag-Pd alloy cluster was synthesized using a one-pot solution-phase route. The crude product upon chromatographic analyses under optimized conditions gave three distinct clusters with unique optical features. One of these exhibits a molecular peak centered at m/z 2839, in its negative ion mass spectrum assigned to Ag5Pd4(SePh)12(-), having an exact match with the corresponding calculated spectrum. Tandem mass spectrometry of the molecular ion peak up to MS(9) was performed. Complex isotope distributions in each of the mass peaks confirmed the alloy composition. We find the Ag3Pd3(-) core to be highly stable. The composition was further supported by scanning electron microscopy, energy-dispersive spectroscopy, and X-ray photoelectron spectroscopy. PMID- 26278747 TI - 8.6% Efficient CZTSSe Solar Cells Sprayed from Water-Ethanol CZTS Colloidal Solutions. AB - Copper zinc tin sulfide-selenide, Cu2ZnSn(S1-xSex)4 (CZTSSe), thin film photovoltaic devices were fabricated using a fast and environmentally friendly preparation method, consisting of the following steps: An instantaneous synthesis of a Cu-Zn-Sn-S (no Se) colloid, a nonpyrolytic spray of a dispersion of this colloid in a water-ethanol mixture, and a sequential annealing first in a N2 atmosphere and second in a Se atmosphere. The achievement of cell efficiencies up to 8.6% under AM1.5G (cell area 0.25 cm(2)) and without antireflecting coating indicates that this method can compete with other vacuum-based or more complex wet deposition methods. PMID- 26278748 TI - Dissociation Pathways of Benzylpyridinium "Thermometer" Ions Depend on the Activation Regime: An IRMPD Spectroscopy Study. AB - The dissociation of benzylpyridinium "thermometer" ions is widely used to calibrate the internal energy of ions produced in mass spectrometry. The fragmentation mechanism is usually believed to yield a benzylium cation, although recent studies suggest the possibility of a rearrangement leading to the tropylium isomer, which would compromise the accuracy of energy calibrations. In this study, we used IRMPD spectroscopy to probe the dissociation pathways of the p-(tert-butyl)benzylpyridinium ion. Our results show that the formation of both benzylium and tropylium products is feasible depending on the activation regime and on the reaction time scale. Varying the trapping delays in the hexapole gives insight into a rearrangement mechanism occurring through consecutive reactions with an isomerization from benzylium to tropylium. Our work provides experimental validations for the established calibration procedure and highlights the adequacy of IRMPD spectroscopy to qualitatively resolve gas-phase rearrangement kinetics. PMID- 26278749 TI - The Power of Two: Covalent Coupling of Photostabilizers for Fluorescence Applications. AB - Fluorescence is a versatile tool for spectroscopic investigations and imaging of dynamic processes and structures across various scientific disciplines. The photophysical performance, that is, signal stability and signal duration, of the employed fluorophores is a major limiting factor. In this Letter, we propose a general concept to covalently link molecules, which are known for their positive effect in photostabilization, to form a combined photostabilizer with new properties. The direct linkage of two (or more) photostabilizers will allow one to obtain combined or synergetic effects in fluorophore stabilization and can simplify the preparation of imaging buffers that would otherwise require a mixture of photostabilizers for optimal performance. This concept was explored by synthesizing a molecule with a reducing and oxidizing moiety that is referred to as internal ROXS or "iROXS". Using single-molecule fluorescence microscopy, inter and intramolecular healing of iROXS was observed, that is, strongly reduced blinking and increased photostability of the cyanine fluorophore Cy5. Moreover, it is shown that a covalently coupled photostabilizer can replace a mixture of molecules needed to make a functional photostabilizing ROXS buffer and might hence represent the new standard for defined and reproducible imaging conditions in single-molecule experiments. In self-healing fluorophores with intramolecular triplet-state quenching, an unprecedented photostability increase of >100-fold was obtained when using iROXS, which is even competitive with solution-based healing. Control experiments show that the oxidizing part of the iROXS molecule, an aromatic nitro group, dominates the healing process. The suggested synthetic concept and the proof-of-concept experiments represent the starting point for the quest to identify optimal combinations of linked photostabilizers for various fluorescence applications. PMID- 26278750 TI - Transition Ion Strikes Back: Large Magnetic Susceptibility Anisotropy in Cobalt(II) Clathrochelates. AB - Transition-metal complexes are rarely considered as paramagnetic tags for NMR spectroscopy due to them generally having relatively low magnetic anisotropy. Here we report cobalt(II) cage complexes with the largest (among the transition metal complexes) axial anisotropy of magnetic susceptibility, reaching as high as 12.6 * 10(-32) m(3) at room temperature. This remarkable anisotropy, which results from an unusual trigonal prismatic geometry of the complexes and translates into large negative value of the zero-field splitting energy, is high enough to promote reliable paramagnetic pseudocontact shifts at the distance beyond 2 nm. Our finding paves the way toward the applications of cobalt(II) clathrochelates as future paramagnetic tags. Given the incredible stability and functionalization versatility of clathrochelates, the fine-tuning of the caging ligand may lead to new chemically stable mononuclear single-molecule magnets, for which magnetic anisotropy is of importance. PMID- 26278751 TI - Connecting the Water Phase Diagram to the Metastable Domain: High-Pressure Studies in the Supercooled Regime. AB - Pressure is extremely efficient to tune intermolecular interactions, allowing the study of the mechanisms regulating, at the molecular level, the structure and dynamics of condensed phases. Among the simplest molecules, water represents in many respects a mystery despite its primary role in ruling most of the biological, physical, and chemical processes occurring in nature. Here we report a careful characterization of the dynamic regime change associated with low density and high-density forms of liquid water by measuring the line shape of the OD stretching mode of HOD in liquid water along different isotherms as a function of pressure. Remarkably, the high-pressure studies have been here extended down to 240 K, well inside the supercooled regime. Supported by molecular dynamics simulations, a correlation among amorphous and crystalline solids and the two different liquid water forms is attempted to provide a unified picture of the metastable and thermodynamic regimes of water. PMID- 26278753 TI - Tailoring the Inherent Optical and Electrical Properties of Nanostructures. PMID- 26278752 TI - Donor-to-Donor vs Donor-to-Acceptor Interfacial Charge Transfer States in the Phthalocyanine-Fullerene Organic Photovoltaic System. AB - Charge transfer (CT) states formed at the donor/acceptor heterointerface are key for photocurrent generation in organic photovoltaics (OPV). Our calculations show that interfacial donor-to-donor CT states in the phthalocyanine-fullerene OPV system may be more stable than donor-to-acceptor CT states and that they may rapidly recombine, thereby constituting a potentially critical and thus far overlooked loss mechanism. Our results provide new insight into processes that may compete with charge separation, and suggest that the efficiency for charge separation may be improved by destabilizing donor-to-donor CT states or decoupling them from other states. PMID- 26278754 TI - Thermal Conductivity of Supercooled Water: An Equilibrium Molecular Dynamics Exploration. AB - The thermal conductivity of both supercooled and ambient-temperature water at atmospheric pressure has been computed over the 140-270 K temperature range for three popular water models via equilibrium molecular dynamics in the Green-Kubo setting. No strong temperature dependence of thermal conductivity was observed. The underlying phonon modes contributing to thermal conduction processes have been examined in the present work, and it has been established that (translational) acoustic modes dominate in supercooled water. PMID- 26278755 TI - Diffusion of Drug Delivery Nanoparticles into Biogels Using Time-Resolved MicroMRI. AB - Nanoparticle-based therapeutic agents can in some cases provide selective delivery to tumors, yet this field would greatly benefit from more detailed understanding of particle transport into and within tumor tissue. To provide fundamental information for optimizing interstitial transport of polymeric nanoparticles, we have developed a quantitative approach employing real-time analysis of nanoparticle diffusion into bulk biological hydrogels using microMRI. We use two distinct imaging approaches to probe the migration of two novel "theranostic" polymeric agents (combining drug delivery and contrast agent functions) into bulk hydrogels. Theranostic agent diffusion measured using time resolved MRI agrees well with diffusion measured for simple probe particles using fluorescence spectroscopies. Furthermore, compared with established fluorescence techniques, which are restricted by sample thickness, our approach provides a three-dimensional diffusion rate and concentration distribution of nanoparticles over macroscopic distances in biological media. These results carry implications for in vivo tracking of theranostic nanoparticles into tumor interstitium. PMID- 26278756 TI - Mechanical Model of DNA Allostery. AB - The importance of allosteric effects in DNA is becoming increasingly appreciated, but the underlying mechanisms remain poorly understood. In this work, we propose a general modeling framework to study DNA allostery. We describe DNA in a coarse grained manner by intra-base pair and base pair step coordinates, complemented by groove widths. Quadratic deformation energy is assumed, yielding linear relations between the constraints and their effect. Model parameters are inferred from standard unrestrained, explicit-solvent molecular dynamics simulations of naked DNA. We applied the approach to study minor groove binding of diamidines and pyrrole-imidazole polyamides. The predicted DNA bending is in quantitative agreement with experiment and suggests that diamidine binding to the alternating TA sequence brings the DNA closer to the A-tract conformation, with potentially important functional consequences. The approach can be readily applied to other allosteric effects in DNA and generalized to model allostery in various molecular systems. PMID- 26278757 TI - The Impact of the Crystallization Processes on the Structural and Optical Properties of Hybrid Perovskite Films for Photovoltaics. AB - We investigate the relationship between structural and optical properties of organo-lead mixed halide perovskite films as a function of the crystallization mechanism. For methylammonium lead tri-iodide, the organic cations rearrange within the inorganic cage, moving from crystals grown in a mesoporous scaffold to larger, oriented crystals grown on a flat substrate. This reduces the strain felt by the bonds forming the cage and affects the motion of the organic cation in it, influencing the electronic transition at the onset of the optical absorption spectrum of the semiconductor. Moreover, we demonstrate that in mixed-halide perovskite, though Cl(-) ions are not present in a detectable concentration in the unit cell, they drive the crystallization dynamics. This induces a preferential order during crystallization, from a molecular, i.e., organic inorganic moieties arrangement, to a nano-mesoscopic level, i.e., larger crystals with anisotropic shape. Finally, we show that while Cl is mainly expelled from flat films made of large crystals, in the presence of an oxide mesoporous scaffold they are partially retained in the composite. PMID- 26278758 TI - Quantum Tunneling Hydrogenation of Solid Benzene and Its Control via Surface Structure. AB - Despite the rapid accumulation of structural information about organic materials, the correlation between the surface structure of these materials and their chemical properties, a potentially important aspect of their chemistry, is not fully understood. Here, we show that the amorphous or crystalline structure of a solid benzene surface controls its chemical reactivity toward hydrogen. In situ infrared spectroscopy revealed that cold hydrogen atoms can add to an amorphous benzene surface at 20 K to form cyclohexane by tunneling. However, hydrogenation is greatly reduced on crystalline benzene. We suggest that the origin of the high selectivity of this reaction is the large difference in geometric constraints between the amorphous and the crystalline surfaces. The present findings can lead us to a more complete understanding of heterogeneous reaction systems, especially those involving tunneling, as well as to the possibility of nonenergetic surface chemical modification without undesired side reactions or physical processes. PMID- 26278759 TI - Morphology and Carrier Extraction Study of Organic-Inorganic Metal Halide Perovskite by One- and Two-Photon Fluorescence Microscopy. AB - The past two years have seen the uniquely rapid emergence of a new class of solar cell-based on mixed organic-inorganic halide perovskite. In this work, we demonstrate a promising technique for studying the morphology of perovskite and its impact on carrier extraction by carrier transport layer using one-photon and two-photon fluorescence imaging in conjunction with time-resolved photoluminescence. This technique is not only effective in separating surface and bulk effects but it also allows the determination of lifetimes in localized regions and local carrier extraction efficiency. The difference in sensitivities of transport materials to grain boundaries and film uniformity is highlighted in this study. It is shown that the PCBM fabricated in this work is more sensitive to film nonuniformity, whereas spiro-OMeTAD is more sensitive to grain boundaries in terms of effective carrier extraction. PMID- 26278760 TI - Dynamics of the Dissociating Uracil Anion Following Resonant Electron Attachment. AB - We report a combined experimental and theoretical investigation of dissociative electron attachment (DEA) to the nucleobase uracil. Using ion momentum imaging experiments employing a DEA reaction microscope we have measured 3-dimensional momentum distributions of specific anionic fragments following DEA to uracil by 6 eV electrons. From the measured anion fragment kinetic energy we determine the possible dissociation pathways and the total kinetic energy release. We employ electronic structure and electron scattering calculations to determine the probability for electron attachment in the molecular frame. Combining these calculations with the imaging measurements, we reveal several key features of the coupled electronic and nuclear dynamics of DEA. PMID- 26278761 TI - Efficient Calculation of Microscopic Dissolution Rate Constants: The Aspirin Water Interface. AB - We present a molecular simulation approach to efficiently determine quantitative rate constants for rare dissolution events from organic crystals. Metadynamics is employed to generate a tailored bias potential that accelerates the escape from the bound state in subsequent hyperdynamics simulations. The robustness and acceleration obtained in the application to kink site dissolution at the aspirin(001)/water interface suggests this technique as a suitable tool to unravel the atomic-scale mechanisms of crystal dissolution. PMID- 26278762 TI - Photoinduced Dynamics in Carbon Nanotube Aggregates Steered by Dark Excitons. AB - Only optically active excitons can be identified by transient absorption spectroscopy, and the actual mechanisms of exciton relaxation in nanoscale systems remain unknown as dipole-forbidden transitions and charge-transfer states are not accounted for. Focusing on interacting (6,4) and (8,4) carbon nanotubes (CNTs), we show that dark excitons largely determine the relaxation pathways for photogenerated excitons in CNT bundles. New channels appear involving asymmetric electron-hole excitations within the same CNT and charge-transfer states, in which the electron and hole are confined to separate CNTs. The energy and charge transfers are facilitated by coupling to both low- and high-frequency phonons. Radial breathing modes are particularly important because they distort the CNT geometry, induce crossings of electronic states, and modulate coupling between CNTs. The time domain simulations reported herein uncover the quantum states and phonon modes that contribute to exciton relaxation in a CNT cluster, elucidating the complete relaxation mechanism. The established role of optically dark states pertains to nonequilibrium dynamics in nanoscale materials in general. PMID- 26278763 TI - Imaging the Stereodynamics of Cl + CH4(nu3 = 1): Polarization Dependence on the Rotational Branch and the Hyperfine Depolarization. AB - The transition state in the Cl + CH4 reaction is of Cl-H-C collinear geometry, which serves as the bottleneck to reaction. When the reactant CH4 is antisymmetrically stretch-excited to nu3 = 1 by absorbing a linearly polarized photon, all four C-H bonds are collectively excited, and any one of the H atoms could be attacked by the Cl atom. At first sight, it is not obvious how an excited spherical-top molecule like CH4 is aligned and what consequences will be on chemical reactivity by polarizing the CH4 reagents. As shown here, an enormous steric effect on reactivity is observed, which depends sensitively on the selected rotational states. By exploiting various rotational branches in optical excitation, we quantify the degree of stereospecificity for a few lowest rovibrational states of the aligned CH4(nu3 = 1) reagents, as well as account for the hyperfine depolarization factor. This information lays the foundation for a full stereorequirement study of the Cl + CH4(nu3 = 1) reaction. PMID- 26278764 TI - Understanding the Reactivity of Layered Transition-Metal Sulfides: A Single Electronic Descriptor for Structure and Adsorption. AB - Density functional theory is used to investigate the adsorption and structural properties of layered transition-metal sulfide (TMS) catalysts. We considered both the (1010) M-edge and (1010) S-edge terminations for a wide range of pure and doped TMSs, determined their sulfur coverage under realistic operating conditions (i.e, steady-state structures), and calculated an extensive set of chemisorption energies for several important reactions. On the basis of these results, we show that the d-band center, epsilond, of the edge-most metal site at 0 ML sulfur coverage is a general electronic descriptor for both structure and adsorption energies, which are known to describe catalytic activity. A negative linear correlation between adsorbate-S binding and S-metal binding allows epsilond to describe the adsorption of species on both metal and sulfur sites. Our results provide a significant simplification in the understanding of structure-activity relationships in TMSs and provides guidelines for the rational design and large-scale screening of these catalysts for various processes. PMID- 26278765 TI - Thermal Dihydrogen Activation by a Closed-Shell AuCeO2(+) Cluster. AB - Laser-ablation-generated AuCeO2(+) and CeO2(+) oxide clusters were mass-selected using a quadrupole mass filter and reacted with H2 in an ion trap reactor at ambient conditions. The reactions were characterized by mass spectrometry and density functional theory calculations. The gold-cerium bimetallic oxide cluster AuCeO2(+) is more reactive in H2 activation than the pure cerium oxide cluster CeO2(+). The gold atom is the active adsorption site and facilitates the heterolytic cleavage of H2 in collaboration with the separated O(2-) ion of the CeO2 support. To the best of our knowledge, this is the first example of thermal H2 activation by a closed-shell atomic cluster, which provides molecular-level insights into the single gold atom catalysis over metal oxide supports. PMID- 26278766 TI - Intramolecular Interactions of Highly pi-Conjugated Perylenediimide Oligomers Probed by Single-Molecule Spectroscopy. AB - Highly pi-conjugated perylenediimide (PDI) oligomers are promising low band gap organic materials for various applications in optoelectronics. In this work, individual fluorescence dynamics of ethynylene- and butadiynylene-bridged dimeric and trimeric PDIs (PEP, PBP, and PEPEP) were monitored and analyzed by single molecule fluorescence spectroscopy to gain information on the degree of extension of pi-conjugation through the acetylene bridge in PDI multichromophores. The simultaneous measurements of fluorescence intensity, lifetime, and spectrum indicate a sequential decrease in pi-conjugation upon photobleaching of PDI monomer units. Furthermore, Huang-Rhys (HR) factors, S, are obtained to evaluate the degree of electronic coupling in view of pi-conjugation and overall rigidity between the PDI units in PDI oligomers at the single-molecule level. In addition, butadiynylene-bridged dimeric PDI (PBP) reveals conformational heterogeneity due to the long butadiynylene linker. These results suggest a new way to control the photophysical properties of the PDI multichromophoric system by expansion of pi conjugation and modification with different linker groups. PMID- 26278767 TI - Enhancing the Charge Separation in Nanocrystalline Cu2ZnSnS4 Photocathodes for Photoelectrochemical Application: The Role of Surface Modifications. AB - Cu2ZnSnS4 (CZTS) colloidal inks were employed to prepare thin-film photocathodes that served as a model system to interrogate the effect of different surface treatments, viz. CdS, CdSe, and ZnSe buffer layers along with methylviologen (MV) adsorption, on the photoelectrochemical (PEC) performance using aqueous Eu(3+) redox electrolyte. PEC experiments revealed that ZnSe and CdSe overlayers outperform traditional CdS, and the additional surface modification with MV was found to further boost the charge extraction. By analyzing the photocurrent onset behavior and measuring the open circuit photopotentials, insights are gained into the nature of the observed improvements. While a more favorable conduction band offset rationalizes the improvement offered by CdSe, charge transfer through midgap states is invoked for ZnSe. Improvement offered by MV treatment is clearly caused by both the shifting of the flat-band potential and a charge-transfer mediation effect. Overall, this work suggests promising alternative surface treatments for CZTS photocathodes for PEC energy conversion. PMID- 26278768 TI - Multiple Energy Exciton Shelves in Quantum-Dot-DNA Nanobioelectronics. AB - Quantum dots (QDs) are semiconductor nanocrystallites with multiple size dependent quantum-confined states that are being explored for utilizing broadband radiation. While DNA has been used for the self-assembly of nanocrystals, it has not been investigated for the formation of simultaneous conduction pathways for transporting multiple energy charges or excitons. These exciton shelves can be formed by coupling the conduction band, valence band, and hot-carrier states in QDs with different HOMO-LUMO levels of DNA nucleobases, resulting from varying degrees of conjugation in the nucleobases. Here we present studies on the electronic density of states in four naturally occurring nucleobases (guanine, thymine, cytosine, and adenine), which energetically couple to quantized states in semiconductor QDs. Using scanning tunneling spectroscopy of single nanoparticle-DNA constructs, we demonstrate composite DOS of chemically coupled DNA oligonucleotides and cadmium chalcogenide QDs (CdS, CdSe, CdTe). While perfectly aligned CdTe QD-DNA states lead to exciton shelves for multiple energy charge transport, mismatched energy levels in CdSe QD-DNA introduce intrabandgap states that can lead to charge trapping and recombination. Although further investigations are required to study the rates of charge transfer, recombination, and back-electron transfer, these results can have important implications for the development of a new class of nanobioelectronics and biological transducers. PMID- 26278769 TI - Ballistic Evaporation and Solvation of Helium Atoms at the Surfaces of Protic and Hydrocarbon Liquids. AB - Atomic and molecular solutes evaporate and dissolve by traversing an atomically thin boundary separating liquid and gas. Most solutes spend only short times in this interfacial region, making them difficult to observe. Experiments that monitor the velocities of evaporating species, however, can capture their final interactions with surface solvent molecules. We find that polarizable gases such as N2 and Ar evaporate from protic and hydrocarbon liquids with Maxwell-Boltzmann speed distributions. Surprisingly, the weakly interacting helium atom emerges from these liquids at high kinetic energies, exceeding the expected energy of evaporation from salty water by 70%. This super-Maxwellian evaporation implies in reverse that He atoms preferentially dissolve when they strike the surface at high energies, as if ballistically penetrating into the solvent. The evaporation energies increase with solvent surface tension, suggesting that He atoms require extra kinetic energy to navigate increasingly tortuous paths between surface molecules. PMID- 26278770 TI - Adsorption and Deposition of Li2O2 on TiC{111} Surface. AB - A recent experimental study from Bruce's group demonstrated the feasibility of TiC as a cathode material for Li air battery. We investigate Li2O2 adsorption and deposition on TiC{111} surface by periodic density functional theory calculation. The results showed that, upon interaction with Ti-terminated TiC{111} surface, Li2O2 clusters reassembled into a saturated periodic two atomic layer coating in which each O atom was bonded to three Ti atoms to form a O layer equivalent to the layer formed by O2 surface oxidation, and the Li atoms sat on the top. The atomic arrangement of O and Li layers is the same as that of O2Li1 layers normal to ?0001? direction in Li2O2 crystal structure. Interface models constructed based on this lead showed that the growth of Li2O2 can be continued through a surface conduction mechanism to form Li2O2 coating with lattice parameters almost identical to those of the standard Li2O2 unit cell. The results support the experimental discovery from Bruce's group. PMID- 26278771 TI - Influence of Tetraalkylammonium Cation Chain Length on Gold and Glassy Carbon Electrode Interfaces for Alkali Metal-Oxygen Batteries. AB - Fundamental studies of dioxygen electrochemistry relevant to metal-air batteries commonly require conductive supporting salts, such as tetraalkylammonium, to sustain redox processes in nonaqueous electrolytes. Electrochemical analysis of the formation and oxidation of superoxide on glassy carbon and gold working electrodes has shown a decrease in reversibility and lowering of the oxygen reduction rate constant when tetraalkylammonium cation alkyl chain length is increased. Probing interfacial regions on Au using in situ surface enhanced Raman spectroscopy (SERS) provides evidence that this is caused by the changing adsorption characteristics of tetralkylammonium cations under negative potentials. These effects are heightened with longer alkyl chain lengths, therefore reducing the reversibility of superoxide formation and dioxygen evolution. From these observations it can be established that shorter chain tetraalkylammonium cations while retaining necessary conductive support: (1) enhance reversibility and rate of superoxide formation and oxidation and (2) for in situ SERS, have lower preference for adsorption, thus improving experimental detection of superoxide at the Au electrode interface. PMID- 26278772 TI - Strong Photocurrent Amplification in Perovskite Solar Cells with a Porous TiO2 Blocking Layer under Reverse Bias. AB - We investigate two different types of TiO2 blocking layer (BL) deposition techniques commonly used in solid-state methylammonium lead triiodide perovskite (MaPbI3)-based solar cells. Although these BLs lead to similar photovoltaic device performance, their structure and blocking capability is actually very different. In one case, the "blocking" layer is porous, allowing an intimate contact of the perovskite with the fluorine-doped tin-dioxide (FTO)-covered glass substrate serving as transparent electron collector. This interface between the perovskite and the FTO shows rectifying behavior. Reverse biasing of such a solar cell allows the determination of the valence-band position of the MaPbI3 and the theoretical maximum attainable photovoltage. We show that under reverse bias strong photocurrent amplification is observed, permitting the cell to work as a high-gain photodetector at low voltage. Without BL, the solar-cell performance decreased, but the photocurrent amplification increased. At 1 V reverse bias, the photocurrent amplification is above a factor of 10 for AM 1.5 solar light and over 100 for lower light intensities. PMID- 26278773 TI - Hysteresis Analysis Based on the Ferroelectric Effect in Hybrid Perovskite Solar Cells. AB - The power conversion efficiency (PCE) of CH3NH3PbX3 (X = I, Br, Cl) perovskite solar cells has been developed rapidly from 6.5 to 18% within 3 years. However, the anomalous hysteresis found in I-V measurements can cause an inaccurate estimation of the efficiency. We attribute the phenomena to the ferroelectric effect and build a model based on the ferroelectric diode to explain it. The ferroelectric effect of CH3NH3PbI3-xClx is strongly suggested by characterization methods and the E-P (electrical field-polarization) loop. The hysteresis in I-V curves is found to greatly depend on the scan range as well as the velocity, which is well explained by the ferroelectric diode model. We also find that the current signals show exponential decay in ~10 s under prolonged stepwise measurements, and the anomalous hysteresis disappears using these stabilized current values. The experimental results accord well with the model based on ferroelectric properties and prove that prolonged stepwise measurement is an effective way to evaluate the real efficiency of perovskite solar cells. Most importantly, this work provides a meaningful perspective that the ferroelectric effect (if it really exists) should be paid special attention in the optimization of perovskite solar cells. PMID- 26278774 TI - Anti-tumour necrosis factor treatment of severe psoriasis complicated by Epstein Barr Virus hepatitis and subsequently by chronic hepatitis. AB - A case is described of severe acute hepatitis in 47-year-old woman with chronic psoriasis and psoriatic arthritis treated with infliximab. Although clinical, serological and laboratory results were compatible with acute EBV hepatitis, it was difficult to differentiate between EBV infection and other non-infectious causes of hepatitis. The patient gradually developed chronic hepatitis with liver steatosis and efficient treatment with adalimumab had to be stopped. This case presents an uncommon complication that may arise from the use of biologic therapy and calls for caution in long-term management of psoriatic patients with internal comorbidities. PMID- 26278775 TI - Long-Lasting and Efficient Tumor Imaging Using a High Relaxivity Polysaccharide Nanogel Magnetic Resonance Imaging Contrast Agent. AB - Clinically approved small-molecule magnetic resonance imaging (MRI) contrast agents are all rapidly cleared from the body and offer weak signal enhancement. To avoid repeated administration of contrast agent and improve signal-to-noise ratios, agents with stronger signal enhancement and better retention in tumors are needed. Therefore, we focused on hydrogels because of their excellent water accessibility and biodegradability. Gadolinium (Gd)-chelating cross-linkers were incorporated into self-assembled pullulan nanogels to both impart magnetic properties and to stabilize this material that has been extensively studied for medical applications. We show that these Gd-chelating pullulan nanogels (Gd CHPOA) have the highest reported relaxivity for any hydrogel-based particles and accumulate in the 4T1 tumors in mice at high levels 4 h after injection. This combination offers high signal enhancement and lasts up to 7 days to delineate the tumor clearly for longer imaging time scales. Importantly, this long-term accumulation does not cause any damage or toxicity in major organs up to three months after injection. Our work highlights the clinical potential of Gd-CHPOA as a tumor-imaging MRI contrast agent, permitting tumor identification and assessment with a high signal-to-background ratio. PMID- 26278776 TI - Conservation of Mass: An Important Tool in Renal Research. AB - The dialytic treatment of end-stage renal disease (ESRD) patients is based on control of solute concentrations and management of fluid volume. The application of the principal of conservation of mass, or mass balance, is fundamental to the study of such treatment and can be extended to chronic kidney disease (CKD) in general. This review discusses the development and use of mass conservation and transport concepts, incorporated into mathematical models. These concepts, which can be applied to a wide range of solutes of interest, represent a powerful tool for quantitatively guided studies of dialysis issues currently and into the future. Incorporating these quantitative concepts in future investigations is key to achieving positive control of known solutes, and in the analysis of such studies; to relate future research to known results of prior studies; and to help in the understanding of the obligatory physiological perturbations that result from dialysis therapy. PMID- 26278777 TI - Independent risk factors for mortality in patients with chronic obstructive pulmonary disease who undergo comprehensive cardiac evaluations. AB - BACKGROUND: Cardiovascular disease is the most common cause of death in chronic obstructive pulmonary disease (COPD). However, the impact of cardiovascular comorbidities on the prognosis of COPD is not well known. OBJECTIVES: This study was performed to investigate the effects of cardiovascular comorbidities on the prognosis of COPD. METHODS: We enlisted 229 patients with COPD who underwent comprehensive cardiac evaluations including coronary angiography and echocardiography at Ajou University Hospital between January 2000 and December 2012. Survival analyses were performed in this retrospective cohort. RESULTS: Kaplan-Meier analyses showed that COPD patients without left heart failure (mean survival = 12.5 +/- 0.7 years) survived longer than COPD patients with left heart failure (mean survival = 6.7 +/- 1.4 years; p = 0.003), and the survival period of nonanemic COPD patients (mean survival = 13.8 +/- 0.8 years) was longer than that of anemic COPD patients (mean survival = 8.3 +/- 0.8 years; p < 0.001). The survival period in COPD with coronary artery disease (CAD; mean survival = 11.37 +/- 0.64 years) was not different from that in COPD without CAD (mean survival = 11.98 +/- 0.98 years; p = 0.703). According to a multivariate Cox regression model, a lower hemoglobin level, a lower left ventricular ejection fraction, and the forced expiratory volume in 1 s (FEV1) were independently associated with higher mortality in the total COPD group (p < 0.05). CONCLUSIONS: Hemoglobin levels and left ventricular ejection fraction along with a lower FEV1 were identified as independent risk factors for mortality in COPD patients who underwent comprehensive cardiac evaluations, suggesting that multidisciplinary approaches are required in the care of COPD. PMID- 26278778 TI - Genome-wide DNA polymorphisms in low Phosphate tolerant and sensitive rice genotypes. AB - Soil Phosphorus (P) deficiency is one of the major challenges to rice crop world wide. Modern rice genotypes are highly P-responsive and rely on high input of P fertilizers. However, low P tolerant traditional cultivars and landraces have genetic potential to sustain well under low P. Identification of high resolution DNA polymorphisms (SNPs and InDels) in such contrasting genotypes is largely missing for low P response at gene levels. Here, we report high quality DNA polymorphisms in low P sensitive genotype, PB1 and tolerant traditional genotype, Dular. We performed whole genome resequencing using Illumina NGS platform and identified a total of 5,157,939 sequence variants in PB1 and Dular with reference to Nipponbare genome. We have identified approximately 2.3 million and 2.9 million high quality polymorphisms in PB1 and Dular, respectively, with an average read depth of >=24X. We further mapped several DNA polymorphisms (non synonymous and regulatory variants) having potential functional significance to key Phosphate Starvation Responsive (PSR) and root architecture genes in Dular and Kasalath using a compiled list of low P responsive genes. These identified variants can serve as a useful source of genetic variability for improving low P tolerance and root architecture of high yielding modern genotypes. PMID- 26278779 TI - Increasing microscopy resolution with photobleaching and intensity cumulant analysis. AB - Super-resolution fluorescence microscopy and its applications for analysis of biological structures are evolving rapidly field. A number of approaches aimed at overcoming the fundamental limit imposed by diffraction have been proposed in recent years. Here we present a modification of super-resolution optical fluctuation imaging (SOFI), a technique based on spatio-temporal evaluation of the optical signal from independently fluctuating emitters. Instead of rapid, reversible photoswitching, photobleaching is used to produce irreversible transitions between emitting and nonemitting states of the fluorochrome molecules. Simulated images are used to demonstrate that, in the absence of noise, the proposed SOFI modification increases the efficiency of transfer of high spatial frequencies in a fluorescence microscope. Correspondingly, a decrease of the point spread function (PSF) width is obtained. Moreover, the modified SOFI algorithm is capable of resolving point emitters in the presence of simulated noise. Using real biological images we demonstrate that an increase of resolution is obtained in 2D optical sections through densely packed chromatin in cell nuclei and lamin layer at the nuclear envelope. Finally, the approach is extended to 3D wide-field microscopy, allowing reduction of out-of-focus image blurring. PMID- 26278780 TI - A 1-Year Clinical and Radiographic Study on Hydrophilic Dental Implants Placed with and without Bone Augmentation Procedures. AB - PURPOSE: The aim of the present 1-year clinical and radiographic study was to evaluate a hydrophilic dental implant when used in everyday cases in one clinic. The purpose was also to compare augmented with nonaugmented sites. MATERIALS AND METHODS: The study group consisted of 50 consecutive patients treated with 159 dental implants (Proactive, Neoss Ltd, Harrogate, UK) in both mandibles and maxillae. Ninety-two implants were placed with adjunct bone augmentation procedures, whereas 40 implants were placed in augmented maxillary sinus sites. A two-stage procedure was used for 84 implants and a one-stage procedure for 47 implants. Twenty-eight implants were immediately loaded. Implant stability was measured with resonance frequency analysis (RFA) at placement and at prosthesis delivery. The patients were scheduled for checkups after 6 and 12 months in function with clinical and radiographic examinations. Marginal bone level measurements were performed in baseline and follow-up intraoral radiographs. RESULTS: Two implant failures in two patients were experienced after 1 year of loading, giving a survival rate of 98.7%. One implant in nonaugmented sites and one implant in conjunction with an augmentation procedure (sinus lift), giving a survival rate of 98.5% and 98.9% for healed and augmented sites, respectively (NS). RFA measurements showed 70.2 +/- 9.5 ISQ at placement and 76.5 +/- 5.9 ISQ (p <= 0.001) after a mean healing time of 5.6 +/- 1.6 months. The marginal bone loss amounted to 0.7 +/- 0.7 mm after 1 year of loading. Frequency distribution showed bone gain or less than 1 mm bone loss for the majority of implants (69.3%), whereas 25.7% showed 1.1 to 2 mm, 5.0% more than 2 mm and no implants more than 3 mm of bone loss. CONCLUSIONS: The use of Neoss Proactive implants for prosthetic rehabilitation of consecutive patients resulted in predictable clinical and radiographic outcomes after 1 year of loading with no differences between augmented and nonaugmented sites. PMID- 26278782 TI - The dopamine D3 receptor: From preclinical studies to the treatment of psychiatric disorders. PMID- 26278783 TI - Erratum. AB - Use of probe-based confocal laser endomicroscopy (pCLE) in gastrointestinal applications. A consensus report based on clinical evidence by Galmiche et al., United European Gatroenterology Journal June 2015; 3: 230-254, doi: 10.1177/2050640614566066. PMID- 26278781 TI - Cell shape dynamics during the staphylococcal cell cycle. AB - Staphylococcus aureus is an aggressive pathogen and a model organism to study cell division in sequential orthogonal planes in spherical bacteria. However, the small size of staphylococcal cells has impaired analysis of changes in morphology during the cell cycle. Here we use super-resolution microscopy and determine that S. aureus cells are not spherical throughout the cell cycle, but elongate during specific time windows, through peptidoglycan synthesis and remodelling. Both peptidoglycan hydrolysis and turgor pressure are required during division for reshaping the flat division septum into a curved surface. In this process, the septum generates less than one hemisphere of each daughter cell, a trait we show is common to other cocci. Therefore, cell surface scars of previous divisions do not divide the cells in quadrants, generating asymmetry in the daughter cells. Our results introduce a need to reassess the models for division plane selection in cocci. PMID- 26278784 TI - The Effectiveness of a Patient-Centred Assessment with a Solution-Focused Approach (DIALOG+) for Patients with Psychosis: A Pragmatic Cluster-Randomised Controlled Trial in Community Care. AB - BACKGROUND: DIALOG+ was developed as a computer-mediated intervention, consisting of a structured assessment of patients' concerns combined with a solution-focused approach to initiate change. This study tested the effectiveness of DIALOG+ in the community treatment of patients with psychosis. METHOD: This was a pragmatic, exploratory, parallel-group, cluster-randomised controlled trial. Clinicians within community teams - along with patients with psychosis under their care - were randomised to use DIALOG+ once per month for 6 months or an active control. The primary outcome (subjective quality of life, SQOL) and secondary outcomes were assessed after 3, 6 and 12 months by blinded assessors and analysed using mixed-effect models. RESULTS: A total of 49 clinicians and 179 patients were randomised. Implementation of DIALOG+ was variable, with an average of 1.8 sessions (SD = 1.6) in the first 3 months and 1.1 (SD = 1.2) in the following 3 months. Patients in the DIALOG+ arm had better SQOL at 3, 6 and 12 months (p = 0.035, 0.058 and 0.014, respectively; Cohen's d = 0.29-0.34). They also had significantly fewer unmet needs at 3 and 6 months, fewer general psychopathological symptoms at all time points and better objective social outcomes at 12 months, with no significant differences in other outcomes. Overall care costs were lower in the intervention group. CONCLUSION: Despite variable implementation, DIALOG+ is a beneficial intervention for community patients with psychosis. As a non-expensive and potentially cost-saving, generic intervention, DIALOG+ may be widely used and may improve the effectiveness of community treatment. Further trials should test DIALOG+ in different patient groups and contexts. PMID- 26278785 TI - What is being measured, and by whom? Facilitation of communication on technical measures amongst competent authorities in the implementation of the European Union Broiler Directive (2007/43/EC). AB - The European Union (EU) Broiler Directive (2007/43/EC) is unique amongst current EU Directives, which address animal welfare, in that it uses outcome data collected at abattoirs and on farm to monitor on-farm broiler welfare and vary the maximum permitted stocking density on farm. In this study, we describe how, by bringing together personnel from the competent authorities in 22 member states (MSs) who have responsibility for implementing the Directive, and engaging in exchange of information and technical methods regarding the Broiler Directive, it has been possible to identify differences in approach with regard to 'what data is being collected, and by whom' across EU MSs. Online questionnaires and workshop exercises enabled us to identify priority areas for knowledge transfer and training. For example, foot pad dermatitis, hock burn, dead on arrival and total rejections (birds rejected as unfit for human consumption by the meat inspection staff at slaughter) were identified by the MSs as measures of medium to-low priority in terms of knowledge transfer because there are assessment methods for these conditions that are already well accepted by competent authorities. On the other hand, breast lesions, cellulitis, emaciation, joint lesions, respiratory problems, scratches, wing fractures and a number of environmental measures were identified as having high priority in terms of knowledge transfer. The study identified that there is significant variability in the stage of implementation between MSs, and responses from the participating MSs indicated that sharing of guidance and technical information between MSs may be of value in the future set-up process for those MSs engaged in implementation of the Directive. PMID- 26278787 TI - Moire induced organization of size-selected Pt clusters soft landed on epitaxial graphene. AB - Two-dimensional hexagonal arrays of Pt nanoparticles (1.5 nm diameter) have been obtained by deposition of preformed and size selected Pt nanoparticles on graphene. This original self-organization is induced, at room temperature, by the 2D periodic undulation (the moire pattern) of graphene epitaxially grown on the Ir(111) surface. By means of complementary techniques (scanning tunneling microscopy, grazing incidence X ray scattering), the Pt clusters shapes and organization are characterized and the structural evolution during annealing is investigated. The soft-landed clusters remain quasi-spherical and a large proportion appears to be pinned on specific moire sites. The quantitative determination of the proportion of organized clusters reveals that the obtained hexagonal array of the almost spherical nanoparticles is stable up to 650 K, which is an indication of a strong cluster-surface interaction. PMID- 26278786 TI - Moyamoya disease susceptibility gene RNF213 links inflammatory and angiogenic signals in endothelial cells. AB - Moyamoya disease (MMD) is a cerebrovascular disorder characterized by occlusive lesions of the circle of Willis. To date, both environmental and genetic factors have been implicated for pathogenesis of MMD. Allelic variations in RNF213 are known to confer the risk of MMD; however, functional roles of RNF213 remain to be largely elusive. We herein report that pro-inflammatory cytokines, IFNG and TNFA, synergistically activated transcription of RNF213 both in vitro and in vivo. Using various chemical inhibitors, we found that AKT and PKR pathways contributed to the transcriptional activation of RNF213. Transcriptome-wide analysis and subsequent validation with quantitative PCR supported that endogenous expression of cell cycle-promoting genes were significantly decreased with knockdown of RNF213 in cultured endothelial cells. Consistently, these cells showed less proliferative and less angiogenic profiles. Chemical inhibitors for AKT (LY294002) and PKR (C16) disrupted their angiogenic potentials, suggesting that RNF213 and its upstream pathways cooperatively organize the process of angiogenesis. Furthermore, RNF213 down-regulated expressions of matrix metalloproteases in endothelial cells, but not in fibroblasts or other cell types. Altogether, our data illustrate that RNF213 plays unique roles in endothelial cells for proper gene expressions in response to inflammatory signals from environments. PMID- 26278789 TI - Outside In: Sequencing the Lung Microbiome. PMID- 26278788 TI - DKK1 rescues osteogenic differentiation of mesenchymal stem cells isolated from periodontal ligaments of patients with diabetes mellitus induced periodontitis. AB - Multiple studies have shown that diabetes mellitus is an established risk factor for periodontitis. Recently mesenchymal stem cells derived from periodontal ligament (PDLSCs) have been utilized to reconstruct tissues destroyed by chronic inflammation. However, impact of periodontitis with diabetes mellitus on PDLSCs and mechanisms mediating effects of complex microenvironments remain poorly understood. In this study, we found multiple differentiation potential of PDLSCs from chronic periodontitis with diabetes mellitus donors (D-PDLSCs) was damaged significantly. Inhibition of NF-kappaB signaling could rescue osteogenic potential of PDLSCs from simple chronic periodontitis patients (P-PDLSCs), whereas did not promote D-PDLSCs osteogenesis. In addition, we found expression of DKK1 in D-PDLSCs did not respond to osteogenic signal and decreased osteogenic potential of D-PDLSCs treated with DKK1 could be reversed. To further elucidate different character between P-PDLSCs and D-PDLSCs, we treated PDLSCs with TNF alpha and advanced glycation end products (AGEs), and find out AGEs which enhance effect of TNF-alpha in PDLSCs might mediate special personality of D-PDLSCs. The adverse effect of AGEs in PDLSCs could be reversed when PDLSCs were treated with DKK1. These results suggested DKK1 mediating WNT signaling might be a therapy target to rescue potential of PDLSCs in periodontitis with diabetes mellitus. PMID- 26278790 TI - The Implications of a Tracheostomy for Discharge Destination. PMID- 26278791 TI - Ultrathin Is In: A New Option for Peripheral Pulmonary Nodules. PMID- 26278792 TI - Upper Room Germicidal Ultraviolet Systems for Air Disinfection Are Ready for Wide Implementation. PMID- 26278793 TI - Diagnosis of Tuberculosis in Children Using Mycobacteria-Specific Cytokine Responses. Are There Reasons for Hope? PMID- 26278794 TI - Tuberculosis and World War I. PMID- 26278795 TI - Update in Sleep Medicine 2014. PMID- 26278797 TI - Isolated Unilateral Absence of the Pulmonary Artery. PMID- 26278796 TI - An Official American Thoracic Society Research Statement: A Research Framework for Pulmonary Nodule Evaluation and Management. AB - BACKGROUND: Pulmonary nodules are frequently detected during diagnostic chest imaging and as a result of lung cancer screening. Current guidelines for their evaluation are largely based on low-quality evidence, and patients and clinicians could benefit from more research in this area. METHODS: In this research statement from the American Thoracic Society, a multidisciplinary group of clinicians, researchers, and patient advocates reviewed available evidence for pulmonary nodule evaluation, characterized six focus areas to direct future research efforts, and identified fundamental gaps in knowledge and strategies to address them. We did not use formal mechanisms to prioritize one research area over another or to achieve consensus. RESULTS: There was widespread agreement that novel tests (including novel imaging tests and biopsy techniques, biomarkers, and prognostic models) may improve diagnostic accuracy for identifying cancerous nodules. Before they are used in clinical practice, however, better evidence is needed to show that they improve more distal outcomes of importance to patients. In addition, the pace of research and the quality of clinical care would be improved by the development of registries that link demographic and nodule characteristics with patient-level outcomes. Methods to share data from registries are also necessary. CONCLUSIONS: This statement may help researchers to develop impactful and innovative research projects and enable funders to better judge research proposals. We hope that it will accelerate the pace and increase the efficiency of discovery to improve the quality of care for patients with pulmonary nodules. PMID- 26278798 TI - Preterm Birth with Childhood Asthma: The Role of Degree of Prematurity and Asthma Definitions. PMID- 26278800 TI - Antipsychotic Agents and Delirium. PMID- 26278799 TI - A Step toward an Optimized Rifampin Dose Completed. PMID- 26278802 TI - Echocardiographic Air Bubbles. Early Sign of Intestinal Pneumatosis. PMID- 26278801 TI - Reply: Antipsychotic Agents and Delirium. PMID- 26278803 TI - PATIENT EDUCATION | INFORMATION SERIES. Sleep Studies: In the Sleep Laboratory and in the Home. PMID- 26278804 TI - A Stepping Stone Toward Personalized Oncology: Genomic Analysis of Circulating Tumor Cells to Guide Management of Metastatic Castration-resistant Prostate Cancer. PMID- 26278806 TI - Three Genes to Predict Response to Chemotherapy for Bladder Cancer: Individualised Cancer Care at the Doorstep. PMID- 26278807 TI - Intra- and inter-observer variability of uterine measurements with three dimensional ultrasound and implications for clinical practice. AB - Despite the emergence of new classifications, the best way to measure and differentiate between the most common congenital uterine anomalies remains debatable. The aim of this study was to test the intra- and inter-observer variability of the different three-dimensional ultrasound (3DUS) uterine measurements described to date. Twenty consecutive women underwent 3DUS in a standardized manner. Two observers analysed each volume three times to assess the interostial distance, indentation distance, indentation angle, percentage of indentation, fundal wall thickness, and lateral wall thickness. Intra- and inter class correlation coefficients (intra- and inter-CC), limits of agreement (LOA) and repeatability coefficients were estimated. For observers 1 and 2, the intra observer reproducibility was the lowest for the left lateral wall thickness (intra-CC 0.91 [LOA -6.54 to 7.10] and 0.58 [LOA -6.58 to 6.94], respectively) and right lateral wall thickness (intra-CC 0.92 [LOA -5.68 to 4.74] and 0.56 [LOA -6.79 to 5.59], respectively). The inter-observer reproducibility was also the lowest for both these measurements (inter-CC 0.74 [LOA -4.01 to 6.09] and 0.72 [LOA -3.33 to 5.83], respectively). The remaining measurements showed high levels of intra- and inter-observer reproducibility (intra- and inter-CC >=0.95). It is evident that not all uterine measurements are equally reproducible on 3DUS. PMID- 26278805 TI - Genomic Characterization of Upper Tract Urothelial Carcinoma. AB - BACKGROUND: Despite a similar histologic appearance, upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) tumors have distinct epidemiologic and clinicopathologic differences. OBJECTIVE: To investigate whether the differences between UTUC and UCB result from intrinsic biological diversity. DESIGN, SETTING, AND PARTICIPANTS: Tumor and germline DNA from patients with UTUC (n=83) and UCB (n=102) were analyzed using a custom next generation sequencing assay to identify somatic mutations and copy number alterations in 300 cancer-associated genes. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We described co-mutation patterns and copy number alterations in UTUC. We also compared mutation frequencies in high-grade UTUC (n=59) and high-grade UCB (n=102). RESULTS AND LIMITATIONS: Comparison of high-grade UTUC and UCB revealed significant differences in the prevalence of somatic alterations. Genes altered more commonly in high-grade UTUC included FGFR3 (35.6% vs 21.6%; p=0.065), HRAS (13.6% vs 1.0%; p=0.001), and CDKN2B (15.3% vs 3.9%; p=0.016). Genes less frequently mutated in high-grade UTUC included TP53 (25.4% vs 57.8%; p<0.001), RB1 (0.0% vs 18.6%; p<0.001), and ARID1A (13.6% vs 27.5%; p=0.050). Because our assay was restricted to genomic alterations in a targeted panel, rare mutations and epigenetic changes were not analyzed. CONCLUSIONS: High-grade UTUC tumors display a spectrum of genetic alterations similar to high-grade UCB. However, there were significant differences in the prevalence of several recurrently mutated genes including HRAS, TP53, and RB1. As relevant targeted inhibitors are being developed and tested, these results may have important implications for the site-specific management of patients with urothelial carcinoma. PATIENT SUMMARY: Comparison of next-generation sequencing of upper tract urothelial carcinoma (UTUC) with urothelial bladder cancer identified that similar mutations were present in both cancer types but at different frequencies, indicating a potential need for unique management strategies. UTUC tumors were found to have a high rate of mutations that could be targeted with novel therapies. PMID- 26278808 TI - Combination of ovarian tissue harvesting and immature oocyte collection for fertility preservation increases preservation yield. AB - The aim of this study was to evaluate the safety and efficacy of combined ovarian tissue cryopreservation and oocyte aspiration just before ovarian tissue cryobanking. A retrospective cohort study of fertility preservation patients treated in 2007-2013 in one tertiary centre was performed. A total of 255 cancer patients were admitted for fertility preservation: 142 patients underwent ovarian tissue cryopreservation only (OTC), 56 underwent OTC plus oocyte retrieval from ovarian tissue (OTIVM), nine underwent oocyte aspiration and in-vitro maturation (AIVM) and 48 underwent all three procedures. The total number of oocytes, total number of metaphase II (MII) oocytes, maturation rate, fertilization rate and total number of cryopreserved oocytes between groups were compared. The study found significantly more oocytes (P < 0.001), more MII oocytes (P < 0.001), better maturation rate (P < 0.01) and more cryopreserved oocytes (P < 0.05) with all three compared with OTIVM or OTC. No adverse outcome was observed by performing oocyte retrieval before ovarian resection for cryopreservation. In conclusion, oocyte aspiration just before ovarian tissue cryobanking is safe and gains more oocytes with a better maturation rate than ovarian tissue oocyte cryobanking alone. Better results were obtained with 3 days of stimulation before oocyte retrieval. PMID- 26278809 TI - Sperm DNA fragmentation is related to sperm morphological staining patterns. AB - In this prospective comparative study, sperm DNA fragmentation (sDNAfrag) was compared at each step of a sequential semen preparation, with semen parameters according to their degree of severity. At each step (fractions) of the sequential procedure, sDNAfrag was determined: fresh (Raw), after gradient centrifugation, washing, and swim-up (SU) for 70 infertile men enrolled in intracytoplasmic sperm injection cycles. sDNAfrag significantly (P = 0.04; P < 0.0001) decreased throughout the steps of semen preparation, with centrifugation and washing not increasing it. A negative correlation to sperm motility was observed in Raw and SU fractions, and a higher sDNAfrag was observed in samples with lower semen quality. Our results confirm that the steps of the sequential procedure do not compromise sperm DNA integrity and progressively decreased sDNAfrag regardless of the sperm abnormality and that semen parameters with lower quality present higher sDNAfrag. Four distinct patterns were observed, of which the entire sperm head staining was the pattern most expressed in all studied fractions. Additionally, the sperm head gene-rich region staining pattern was reduced by the procedure. This suggests that pattern quantification might be a useful adjunct when performing sDNAfrag testing for male infertility. PMID- 26278810 TI - 'By the work, one knows the workman': the practice and profession of the embryologist and its translation to quality in the embryology laboratory. AB - The embryologist presides over the fulfillment of a patient's treatment in the laboratory for IVF through use of assisted reproduction techniques, and is in a unique position to impart quality to the process. Although the technical skill of the embryologist is critical, the embryologist's contribution to quality is equally conveyed through a knowledge of reproductive biology, keen observation and judgment, astute decision-making, the 'grit' to work under pressure and time constraints, and a sense of mission in the provision and continual development of a safe and effective laboratory. The embryologist also ensures that the laboratory complies with the regulations of federal, state, local and institutional authorities and the recommendations and guidelines of professional associations. In these roles, the embryologist assumes unique responsibilities counterbalanced by the unique rewards of assisting patients in having a family. This article aspires to illuminate this singular profession for those who may be contemplating a career in embryology and act as a resource for those who seek insight into this amalgam of basic science, technical proficiency, and managerial skill and acumen that characterize the practice of clinical embryology and the myriad of ways that practitioners contribute to the quality of assisted reproduction techniques and patient care. PMID- 26278811 TI - In vitro genotoxicity tests point to an unexpected and harmful effect of a Magnolia and Aristolochia association. AB - ETHNOPHARMACOLOGICAL RELEVANCE: in the 1990s, a Belgian cohort of more than 100 patients reported cases of Aristolochic Acid Nephropathy (AAN). This progressive renal and interstitial fibrosis, frequently associated with urothelial malignancies, was consecutive to the Chinese-herbs based slimming capsules intake where a plant Stephania tetrandra S. Moore was replaced by a highly genotoxic Aristolochia species. 70% of the Belgian patients evolved into end-stage renal disease, requiring dialysis or renal transplantation. Furthermore the prevalence of upper urinary tract carcinoma was found alarmingly high in these patients. The Aristolochia adulteration was blamed for the intoxication cases and, to the best of our knowledge, the prescription itself has not been further investigated. AIM OF THE STUDY: This work proposes to evaluate the in vitro cytotoxicity and genotoxicity of Aristolochia and Magnolia traditional aqueous decoctions and their association. MATERIALS AND METHODS: The cytotoxicity of extracts has been assessed by a MTT cell proliferation assay and the genotoxicity by measuring the presence of gamma-H2AX, a phosphorylated histone associated with DNA damages. RESULTS: Treating cells for 24h with a mixture 1:1 of Magnolia officinalis and Aristolochia baetica decoctions led to an increase in the production of gamma H2AX. CONCLUSIONS: This genotoxic potentiation warrants further studies but may lead to an explanatory factor for the "Chinese herb nephropathy" cases. PMID- 26278812 TI - Ethnomedicinal plants of Aydincik District of Mersin, Turkey. AB - ETHNOPHARMACOLOGICAL RELEVANCE: This survey presents crucial ethnopharmacological data on medicinal plants used by indigenous people who live in the Aydincik district of Mersin in Turkey. AIM OF THE STUDY: To provide a knowledge base of herbal therapies from the Aydincik region with their traditional use, plant parts and administration methods besides computing some statistical values. MATERIALS AND METHODS: Plant samples that have been collected by spice-sellers or residents from Aydincik for therapeutic purposes were recorded by visiting the villages during the study period, and then brought to the laboratory to diagnose the taxa. In addition, the relative frequency citation (RFC), use values (UV), informant consensus factor (ICF) and fidelity level (FL) were computed. RESULTS: In this research conducted between 2013 and 2015, 91 taxa associated with 41 families, including 1 fern & 2 gymnosperms were defined they have been used for centuries in terms of the healing by visiting 10 villages & 5 spice-sellers in Aydincik. Lamiaceae, Rosaceae, Araceae, Asteraceae, Cupressaceae, Orchidaceae and Pinaceae have been determined as the most used families for therapeutic purposes. The study revealed that most of the locals concurred on the use of Juniperus oxycedrus fruits & leaves to cure gastro-intestinal diseases that demonstrated the highest fidelity level (0.98). 22 taxa have not matched with any studies conducted in and around the region. CONCLUSION: The light of the information obtained during the investigation demonstrates that the medicinal plants have been mostly utilized as analgesics (0.78 ICF). The most data were acquired from the mountain villagers & Yuruk nomads, having average ages of 65. From the viewpoint of ethnobotany, the district has remained valuable due to the winding roads, ongoing hundreds of kilometers over the mountains and along the coast is very difficult to drive making Aydincik too far from large cities and mass tourism centers. PMID- 26278813 TI - The Middle East respiratory syndrome puzzle: A familiar virus, a familiar disease, but some assembly still required. PMID- 26278814 TI - Who is less likely to die in association with improved National Emergency Access Target (NEAT) compliance for emergency admissions in a tertiary referral hospital? AB - Objective The aim of the present study was to identify patient and non-patient factors associated with reduced mortality among patients admitted from the emergency department (ED) to in-patient wards in a major tertiary hospital that had previously reported a near halving in mortality in association with a doubling in National Emergency Access Target (NEAT) compliance over a 2-year period from 2012 to 2014. Methods We retrospectively analysed routinely collected data from the Emergency Department Information System (EDIS) and hospital discharge abstracts on all emergency admissions during calendar years 2011 (pre NEAT interventions) and 2013 (post-NEAT interventions). Patients admitted to short-stay wards and then discharged home, as well as patients dying in the ED, were excluded. Patients included in the study were categorised according to age, time and day of arrival to the ED, mode of transport to the ED, emergency triage category, type of clinical presentation and major diagnostic codes. Results The in-patient mortality rate for emergency admissions decreased from 1.9% (320/17022) in 2011 to 1.2% (202/17162) in 2013 (P<0.001). There was no change from 2011 to 2013 in the percentage of deaths in the ED (0.19% vs 0.17%) or those coded as in-patient palliative care (17.9% vs 22.2%). Although deaths were not associated with age by itself, the mortality rate of older patients admitted to medical wards decreased significantly from 3.5% to 1.7% (P=0.011). A higher mortality rate was seen among patients presenting to ED triage between midnight and 12 noon than at other times in 2011 (2.5% vs 1.5%; P<0.001), but this difference disappeared by 2013 (1.3% vs 1.1%; P=0.150). A similar pattern was seen among patients presenting on weekends versus weekdays: 2.2% versus 1.7% (P=0.038) in 2011 and 1.3% versus 1.1% (P=0.150) in 2013. Fewer deaths were noted among patients with acute cardiovascular or respiratory disease in 2013 than in 2011 (1.7% vs 3.6% and 1.5% vs 3.4%, respectively; P<0.001 for both comparisons). Mode of transport to the ED or triage category was not associated with changes in mortality. These analyses took account of any possible confounding resulting from differences over time in emergency admission rates. Conclusions Improved NEAT compliance as a result of clinical redesign is associated with improved in patient mortality among particular subgroups of emergency admissions, namely older patients with complex medical conditions, those presenting after hours and on weekends and those presenting with time-sensitive acute cardiorespiratory conditions. What is known about the topic? Clinical redesign aimed at improving compliance with NEAT and reducing time spent within the ED of acutely admitted patients has been associated with reduced mortality. To date, no study has attempted to identify subgroups of patients who potentially derive the greatest benefit from improved NEAT compliance in terms of reduced risk of in-patient death. It also remains unclear as to what extent non-patient factors (e.g. admission practices and differences in coding of palliative care patients) affect or confound this reduced risk. What does this paper add? The present study is the first to reveal that enhanced NEAT compliance is associated with lower mortality among particular subgroups of emergency patients admitted to in-patient wards. These include older patients with complex medical conditions, those presenting after hours or on weekends or those with time-sensitive acute cardiorespiratory conditions. These results took account of any possible confounding resulting from differences over time in emergency admission rates, deaths in the ED, numbers of short-stay ward admissions and coding of palliative care deaths. What are the implications for practitioners? Efforts aimed at improving NEAT compliance and efficiencies at the ED-in-patient interface appear to be worthwhile in reducing in-patient mortality among particular subgroups of emergency admissions at high risk. More research is urgently needed in identifying patient- and system-level factors that predispose to higher mortality rates in such populations, but are potentially amenable to focused interventions aimed at optimising transitions of care at the ED-in-patient interface and increasing NEAT compliance for patients admitted to in-patient wards from the ED. PMID- 26278815 TI - Detection of mitotic figures in thin melanomas--immunohistochemistry does not replace the careful search for mitotic figures in hematoxylin-eosin stain. AB - BACKGROUND: The mitotic rate is an important prognostic criterion in patients with thin melanoma <= 1 mm. OBJECTIVE: The aim of this study was to investigate the reproducibility of the mitotic rate in thin melanoma in hematoxylin-eosin (H&E) stain and compare it with the detection of mitotic figures by immunohistochemistry. METHODS: The number of mitoses stated in the routine diagnostic report in 190 pT1 melanomas was compared with the number gained from re-evaluation of H&E sections and the number detected after staining with the mitotic marker, phosphohistone H3 (PHH3). Two different approaches were used for choosing the "hot spot" for evaluation (dermal vs epidermal/dermal). RESULTS: Comparing routine H&E-stained slides with re-evaluation slides, the number of mitotic figures was slightly variable. However, findings did not result in a change of the tumor stage. In 34% of the tumors with dermal mitotic figures on H&E, mitoses could not be found in the corresponding PHH3 slide anymore. In 4% of the cases, stage relevant mitoses could only be found by PHH3 immunohistochemistry. LIMITATION: This is a single center study. CONCLUSION: Immunohistochemical staining for mitotic figures does not replace a careful evaluation of H&E-stained slides. Immunohistochemical detection of mitosis is only an additional tool; the time-saving effect is therefore negligible. PMID- 26278816 TI - Expression of hypoxia-inducible factor 1 alpha ameliorate myocardial ischemia in rat. AB - Hypoxia-inducible factor 1 alpha (HIF-1a), the upstream regulator of Vascular endothelial growth factor (VEGF), is the vital hypoxia related gene expression control factor. To evaluate HIF-1a therapeutic efficacy to acute myocardial infarction, the HIF-1a expressing recombinant Adeno-associated virus (rAAV) was constructed. The Wistar rat ischemic heart animal model was established with left anterior descending coronary artery ligation. The ischemic rats were treated with HIF-1a expressing and GFP expressing rAAVs respectively. Four weeks post the injection, the cardiac function of treated rat was compared by TM_WAVE system; size of infracted area was calculated by Evan's blue stain and capillary density was determined by CD31 immunohistochemical staining. Compare to the control group, the rats received HIF-1a expressing rAAV have smaller infracted heart size, the better heart function and higher capillary density than vehicle control group. The results show that the injection of HIF1a expressing rAAV can improve cardiac function and ameliorate acute myocardial ischemia (AMI) in rats. PMID- 26278817 TI - Plasma membrane Ca(2+)-ATPase is a novel target for ketamine action. AB - Ketamine, a high affinity uncompetitive antagonist of voltage-dependent NMDA receptor, has been used for years as a dissociative anesthetic. Although the drug is considered as safe and well-tolerable, it is now evident that it can exert dose-dependent multidirectional effects acting on different cellular targets and pathways. The latest clinical studies also demonstrated its promising antidepressant action. However, the widespread use of this drug in humans is largely limited by a broad range of cognitive adverse effects that resemble some core symptoms of schizophrenia. In line with the hypothesis of unifying role of calcium in schizophrenia symptomology, we used ketamine-induced rat model of experimental psychosis to study the effect of 5-day ketamine treatment (30 mg/kg, ip) on the activity of plasma membrane Ca(2+)-ATPase. Whereas no change in a total amount of the enzyme in cortical synaptosomal membranes was observed, a decrease by ~50% in hydrolytic activity, as well as lowered phosphointermediate formation were detected. Moreover, ketamine action appeared to be isoform independent. The experiments on intact Ca(2+)-ATPase purified from vehicle treated rat cortex revealed dose-dependent inhibition of enzymatic activity. Furthermore, ketamine decreased, but not eliminated, the stimulation by calmodulin. The inhibitory effect, although much weaker, was also evident for truncated form of calcium pump obtained following digestion by trypsin. Our results indicate that plasma membrane Ca(2+)-ATPase is a novel target for ketamine and putative interaction sites may involve central catalytic loop and calmodulin-binding domain. PMID- 26278818 TI - A tryptophan derivative TD-26 attenuates thrombus formation by inhibiting both PI3K/Akt signaling and binding of fibrinogen to integrin alphaIIbbeta3. AB - The incidence and mortality of thrombotic disorders are rapidly increasing worldwide. The existing antithrombotic drugs, however, are associated with side effects, especially bleeding complications. Therefore, there remains a need for the development of more effective and safer antithrombotic agents. In this study, we discovered a new synthetic tryptophan derivative TD-26, producing potent inhibitory effect on platelet aggregation while without causing obvious bleeding risk. It has been shown that TD-26 inhibited platelet aggregation induced by ADP, thrombin, U46619 and collagen in vitro and suppressed the platelet aggregation induced by ADP ex vivo. Mechanism studies indicated that TD-26 inhibited platelet adhesion to fibrinogen-coated surfaces, blocked the binding of fibrinogen to integrin alphaIIbbeta3 and reduced Akt(Ser473) phosphorylation in platelet phosphatidylinositol 3-kinase (PI3K) signaling. Furthermore, TD-26 exhibited potent antithrombotic activity in vivo. In animal models, it decreased death of mice with acute pulmonary thrombosis by 90% and attenuated thrombosis weight by 60.3%, both at a dose of 3 mg/kg. Additionally, TD-26 did not obviously prolong bleeding time in mice. Taken together, our results reveal that TD-26 is a novel antithrombotic compound exhibiting both integrin alphaIIbbeta3 inhibition and PI3K signaling blockage, with a low bleeding risk. PMID- 26278819 TI - Autophagy inhibition sensitizes KU-0063794-mediated anti-HepG2 hepatocellular carcinoma cell activity in vitro and in vivo. AB - Recent studies have indicated that mammalian target of rapamycin (mTOR) signaling has a critical role in the pathogenesis of hepatocellular carcinoma (HCC). In the current study, we investigated the activity of KU-0063794, a novel mTOR kinase inhibitor, against HepG2 HCC cells. Our results demonstrated that KU-0063794 blocked mTOR complex 1/2 (mTORC1/2) activation, and downregulated mTOR-regulated genes (Cyclin D1 and hypoxia-inducible factor 1alpha) in HepG2 cells. Consequently, KU-0063794 induced significant anti-survival and pro-apoptotic activities against HepG2 cells. When analyzing the possible KU-0063794-resistance factors, we showed that KU-0063794 induced cyto-protective autophagy activation in HepG2 cells, evidenced by GFP-light chain 3B (LC3B) puncta formation, p62 degradation, Beclin-1 expression and LC3B-I to LC3B-II conversion. Correspondingly, autophagy inhibitors, including bafliomycin A1, 3-methyladenine (3-MA) and chloroquine, dramatically enhanced KU-0063794-induced cytotoxicity against HepG2 cells. Further, RNAi knockdown of Beclin-1 also increased KU 0063794 sensitivity in HepG2 cells. In vivo, oral administration of KU-0063794 repressed HepG2 xenograft growth in severe combined immunodeficient (SCID) mice, and its activity was further enhanced with co-administration of the autophagy inhibitor 3-MA. In summary, KU-0063794 inhibits HepG2 cell growth in vitro and in vivo, its activity could be further enhanced with autophagy inhibition. PMID- 26278820 TI - One-step extraction of functional recombinant aquaporin Z from inclusion bodies with optimal detergent. AB - Aquaporins are integral membrane channel proteins found in all kingdoms of life. The Escherichia coli aquaporin Z (AqpZ) has been shown to solely conduct water at high permeability. Functional AqpZ is generally purified from the membrane fraction. However, the quantity of the purified protein is limited. In this study, a new method is developed to achieve high yield of bioactive AqpZ protein. A mild detergent n-dodecyl-beta-D-maltopyranoside (DDM) was used to solubilize the over-expressed insoluble AqpZ from inclusion bodies without a refolding process. The recovered AqpZ protein showed high water permeability comparable with AqpZ obtained from the membrane fraction. In this way, the total yield of bioactive AqpZ has been increased greatly, which will facilitate the structural and functional characterization and future applications of AqpZ. PMID- 26278821 TI - Isoform separation of proteins by mixed-mode chromatography. AB - Mixed-mode chromatography uses a multimodal functional resin, mainly composed of electrostatic and aromatic/hydrophobic groups. Here we have tested 2 mixed-mode resins, anion-exchange Capto adhere and cation-exchange Capto MMC, using 2 model proteins, i.e., an Fc-fusion etanercept, and bovine serum albumin (BSA). When etanercept was produced in Chinese hamster ovary cells, a large amount of misfolded species was generated. A novel technology to achieve effective separation of the misfolded or aggregated species has been developed in this study using these mixed-mode columns and elution conditions that combine pH change and NaCl or arginine at different concentrations. Etanercept, which has been purified by Protein-A chromatography, was bound to the Capto MMC or Capto adhere columns under various conditions and eluted by modulating the pH and salt or arginine concentration. The misfolded species occurred in the fractions at higher salt or arginine concentrations, most likely reflecting stronger electrostatic and hydrophobic interactions of the misfolded species with these mixed-mode resins. Another model protein, BSA, containing several oligomeric species, was also subjected to Capto adhere or Capto MMC chromatography using either NaCl or arginine gradient elution, with a greater recovery by arginine gradient. The oligomers were effectively separated on these mixed-mode columns using either gradient elution, eluting in later fractions similar to etanercept misfolded species. PMID- 26278822 TI - Testicular Cystic Walthard Cell Nest in a 7-Month-Old. AB - Walthard cell nests have previously been reported arising from paratesticular structures; however, this is the first reported case of an intratesticular Walthard cell nest. We report our experience with this lesion which is interesting not only because of its extreme rarity but also because of the proposed histogenesis of such lesions. PMID- 26278823 TI - Outcomes of Microscopic Subinguinal Varicocelectomy With and Without the Assistance of Doppler Ultrasound: A Randomized Clinical Trial. AB - OBJECTIVE: To compare the surgical outcomes and complications between microscopic subinguinal varicocelectomy (MV) and intraoperative vascular Doppler ultrasound assisted microscopic subinguinal varicocelectomy (IVDU-MV) for infertile patients with varicoceles. MATERIALS AND METHODS: One hundred seventy-two infertile patients with varicoceles were randomly divided into IVDU-MV group (n = 85) and MV group (n = 87). We assessed patients' operative and postoperative parameters, semen parameters, and the pregnancy rate. The mean follow-up period was 21 months (range, 13-34 months). RESULTS: The operative time was significantly shorter in the IVDU-MV group than MV group (41.9 +/- 13.6 vs 52.7 +/- 14.1 minutes, P <.05). The number of intraoperative arteries spared was significantly greater in the IVDU-MV group than the MV group (1.9 +/- 0.8 vs 1.3 +/- 0.7, P <.05). In addition, the average number of spermatic veins ligated was significantly greater in the IVDU-MV group (7.8 +/- 2.1 vs 7.0 +/- 1.9, P <.05). Lymphatic spared showed no significant difference (P >.05). The postoperative hospital stay showed no significant difference. Sperm concentration, sperm motility, and the percentage of grade a+b sperm were significantly increased in both groups at 3, 6, and 12 months after surgery (P <.05), and the sperm motility was higher in IVDU-MV than MV group (43.98 +/- 7.64 vs 36.98 +/- 5.10, P <.05) in 12 months after surgery. Sperm morphology was comparable between the 2 groups. The pregnancy rate showed no significant difference (36.8% of the MV vs 34.1% of the IVDU-MV, P >.05). CONCLUSION: Our study demonstrated that both MV and IVDU-MV are effective methods for the improvement of semen parameters in infertile men with varicocele, with a natural conception rate of 35% over a mean follow-up of 21 months. Compared with MV, IVDU-MV is superior in shortening operative time, increasing the number of spermatic arteries spared, spermatic veins ligated, and sperm motility after surgery. IVDU should be routinely used as an effective tool to improve outcomes and safety of varicocelectomy. PMID- 26278824 TI - Strangulated Internal Hernia Behind the Common Iliac Artery Following Pelvic Lymph Node Dissection. AB - We report a rare case of a strangulated internal hernia behind the common iliac artery after robot-assisted pelvic lymph node dissection. Internal hernias involving the retroperitoneal vascular axis have been reported four times in medical literature. This is the first time it has been seen after robotic surgery. PMID- 26278825 TI - Efficacy of Phosphodiesterase-5 Inhibitor in Men With Premature Ejaculation: A New Systematic Review and Meta-analysis. AB - OBJECTIVE: To clarify the efficacy of phosphodiesterase-5 inhibitor (PDE5i) in men with premature ejaculation (PE). METHODS: We searched the PubMed, Embase, and Cochrane Library databases to identify all randomized controlled trials and compared results, including intravaginal ejaculation latency time, satisfaction, side effects, and others, after treatment with PDE5i vs placebo, PDE5i vs selective serotonin reuptake inhibitor (SSRI), or combined use of PDE5i with SSRI vs SSRI alone for treating PE. RESULTS: The study inclusion criteria were met by 10 studies (10 randomized controlled trials with 3 crossover studies) involving 775 patients. The data synthesized from these studies indicated that the efficacy of PDE5i was better than that of placebo; however, more patients had side effects while taking PDE5i. The efficacy of PDE5i was better than that of SSRIs, and no significant difference was observed in the frequency of side effects. The efficacy of the combined treatment was significantly better than that of SSRI alone; however, more patients had side effects from the combined treatment. The major limitations of this meta-analysis were that there is no universally agreed definition of PE, and the types of medications differed among the studies evaluated. CONCLUSION: PDE5i was significantly more effective than a placebo or SSRI for treating PE; however, it had more side effects than placebo. The combined treatment of PDE5i and SSRI had better efficacy but more side effects than the use of SSRI alone. PMID- 26278826 TI - Tinea incognito in an old patient with bullous pemphigoid receiving topical high potency steroids. PMID- 26278827 TI - Knowledge, evidence, practice and power. PMID- 26278828 TI - Farewell, but not goodbye!! PMID- 26278829 TI - Historical note: How bringing women's health advocacy groups to WHO helped change the research agenda. AB - The politics of population control and its sometimes coercive methods in developing countries documented during the 1960s, 70s and 80s, gave rise to strong opposition by women's groups, and put into question the safety of contraceptive methods that were being developed and introduced into countries. In 1991, the Special Programme on Human Reproduction at the World Health Organization, a research programme focused on development of new methods and safety assessments of existing fertility regulation methods, started a process of "dialogue" meetings between scientists and women's health advocacy groups which lasted for nearly a decade. This paper describes the process of these meetings and what they achieved in terms of bringing new or different research topics into the agenda, and some of the actions taken as a result. PMID- 26278830 TI - Speaking of sex workers: How suppression of research has distorted the United States' domestic HIV response. AB - Sex workers remain a vulnerable population at risk for HIV acquisition and transmission. Research suggests that interventions at the individual level, such as condom distribution, are less effective in preventing HIV among sex workers than structural changes such as allowing safer work settings and reducing the harassment and abuse of sex workers by clients and police. In the US, HIV incidence has not declined in the last decade. This may be due in part to its policy of wilful ignorance about sex work, but the data to resolve the question simply do not exist. Political actions such as PEPFAR's prostitution pledge and a congressional campaign against "waste, fraud and abuse" in research are products of an ideological environment that suppresses research on HIV prevention and treatment needs of sex workers. Even basic prevalence data are missing because there is no "sex worker" category in the US National HIV Behavior Surveillance System. However, international efforts are taking a public health approach and are calling for decriminalization of sex work, as the most effective public health strategy for reducing HIV incidence among sex workers. Although such an approach is not yet politically feasible in the US, some urgent practical policy changes can be implemented to improve data collection and generation of evidence to support HIV prevention and treatment programs targeting sex workers. PMID- 26278831 TI - Fertility-related research needs among women at the margins. AB - Fertility-related research encompasses fertility intentions, preconception care, research amongst pregnant women, and post-partum outcomes of mothers and children. However, some women remain under-represented within this domain of study. Women frequently missing within fertility-related research include those who are already the most vulnerable to health disparities, including female sex workers, lesbian, gay, bisexual, and transgender women, women living with HIV, and women who use drugs. Yet characterization of the needs of these women is important, given their unique fertility-related concerns, including risks and barriers to care emanating from social stigmas and discrimination. This synthesis provides an overview of fertility-related evidence, highlighting where there are clear research gaps among marginalized women and the potential implications of these data shortfalls. Overall, research among marginalized women to date has addressed pregnancy prevention and in some cases fertility intentions, but the majority of studies have focused on post-conception pregnancy safety and the well being of the child. However, among female sex workers specifically, data on pregnancy safety and the well-being of the child are largely unavailable. Within each marginalized group, preconception care and effectiveness of conception methods are consistently understudied. Ultimately, the absence of epidemiologic, clinical and programmatic evidence limits the availability and quality of reproductive health services for all women and prevents social action to address these gaps. PMID- 26278832 TI - Safe abortion information hotlines: An effective strategy for increasing women's access to safe abortions in Latin America. AB - This paper describes the implementation of five Safe Abortion Information Hotlines (SAIH), a strategy developed by feminist collectives in a growing number of countries where abortion is legally restricted and unsafe. These hotlines have a range of goals and take different forms, but they all offer information by telephone to women about how to terminate a pregnancy using misoprostol. The paper is based on a qualitative study carried out in 2012-2014 of the structure, goals and experiences of hotlines in five Latin American countries: Argentina, Chile, Ecuador, Peru and Venezuela. The methodology included participatory observation of activities of the SAIH, and in-depth interviews with feminist activists who offer these services and with 14 women who used information provided by these hotlines to induce their own abortions. The findings are also based on a review of materials obtained from the five hotline collectives involved: documents and reports, social media posts, and details of public demonstrations and statements. These hotlines have had a positive impact on access to safe abortions for women whom they help. Providing these services requires knowledge and information skills, but little infrastructure. They have the potential to reduce the risk to women's health and lives of unsafe abortion, and should be promoted as part of public health policy, not only in Latin America but also other countries. Additionally, they promote women's autonomy and right to decide whether to continue or terminate a pregnancy. PMID- 26278833 TI - Emergency contraceptive use in Addis Ababa, Ethiopia: Challenging common assumptions about young people's contraceptive practices. AB - Drawing on an ethnographic case study of young people's (aged 18-29) use of emergency contraceptives (ECs) in Addis Ababa, Ethiopia, this article highlights areas of disconnect between how reproductive health experts envision EC use and local meanings ascribed to ECs by young people. ECs - designed by reproductive health experts to be used only in case of emergency - were preferred by study participants over other contraceptive methods because of their ease of use, discreetness, perceived minimal side effects on beauty and future fertility, and usefulness in navigating reproductive intentions. The findings point to features that young people find desirable when it comes to contraceptive methods and suggest that common assumptions of reproductive health experts about young people's contraceptive practices need to be reconsidered, namely: 1) that young people can plan for prevention of unwanted pregnancy by buying a contraceptive method in advance; 2) that existing contraceptive technologies are appropriate for young people; 3) that young people prefer to use modern contraceptive methods; and 4) that young people in premarital relationships aim to prevent unplanned pregnancy. PMID- 26278834 TI - Reasons for routine episiotomy: A mixed-methods study in a large maternity hospital in Phnom Penh, Cambodia. AB - First documented in 1741, the practice of episiotomy substantially increased worldwide during the 20th century. However, research shows that episiotomy is not effective in reducing severe perineal trauma and may be harmful. Using a mixed methods approach, we conducted a study in 2013-14 on why obstetricians and midwives in a large maternity hospital in Phnom Penh, Cambodia, still do routine episiotomies. The study included the extent of the practice, based on medical records; a retrospective analysis of the delivery notes of a random sample of 365 patients; and 22 in-depth interviews with obstetricians, midwives and recently delivered women. Of the 365 women, 345 (94.5%, 95% CI: 91.7-96.6) had had an episiotomy. Univariate analysis showed that nulliparous women underwent episiotomy more frequently than multiparous women (OR 7.1, 95% CI 2.0-24.7). The reasons given for this practice by midwives and obstetricians were: fear of perineal tears, the strong belief that Asian women have a shorter and harder perineum than others, lack of time in overcrowded delivery rooms, and the belief that Cambodian women would be able to have a tighter and prettier vagina through this practice. A restrictive episiotomy policy and information for pregnant women about birthing practices through antenatal classes should be implemented as soon as possible. PMID- 26278835 TI - New actors, financial mechanisms and reformed aid reporting: What role for SRHR in post-2015 financing for development? AB - As governments around the world prepare to adopt a new development framework and supportive financial flows, the OECD Development Assistance Committee is exploring new ways of measuring and reporting on resource flows enabling development, including population assistance. These changes will affect the evidence base, discourse about and donor incentives related to sexual and reproductive health and rights (SRHR). They may lead to: i) reduction of grant aid in favour of instruments that are less suitable for SRHR, like loans and market-like instruments; ii) expansion of the range of development stakeholders to include those with market power that can steer the discussion away from the needs of the most under-served populations; and iii) diversion of attention and resources away from SRHR. The discourse over how to provide, incentivize and report on development assistance in the new framework demonstrates the crucial relationship between knowledge, evidence, practice and power in relation to funding for SRHR in developing countries. With all that is at stake, although the OECD debate on the future of the development finance measurement system may seem highly abstract, this is a high-stakes game that SRHR advocates need to have a hand in. Those who seek to improve SRHR are well served to engage in these discussions as early and often as possible before the momentous decisions over the coming months. PMID- 26278836 TI - Radical or routine? Nurse practitioners, nurse-midwives, and physician assistants as abortion providers. AB - In 2013 California passed legislation that expanded the pool of eligible aspiration abortion providers to include advanced practice nurses, nurse midwives, and physician-assistants. This law, enacted in 2014, is based on evidence generated by the Health Workforce Pilot Project #171, which examined the safety and effectiveness of aspiration abortion care provided by these clinicians as well as patient acceptability and satisfaction. This evidence and the resulting policy change build on international research and established workforce strategies used to expand access to safe abortion services for women worldwide, representing a radical departure from the legislative trend of constricting access in the United States. PMID- 26278837 TI - Sexual and reproductive health and rights and mHealth in policy and practice in South Africa. AB - Information and Communications Technology (ICT) offers enormous opportunity and innovation to improve public health and health systems.This paper explores the intersections between mHealth and sexual and reproductive health and rights in both policy and practice. It is a qualitative study, informed by policy review and key informant interviews. Three case studies provide evidence of what is happening on the ground in relation to ICTs and reproductive health and rights. We argue that in terms of policy, there is little overlap between health rights and communication technology. In the area of practice, however, significant interventions address aspects of reproductive health. At present, the extent to which mHealth addresses the full range of reproductive justice and sexual and reproductive health and rights is limited, particularly in terms of government initiatives. The paper argues that mHealth projects tend to avoid contentious aspects of sexual health, while addressing favourable topics such as pregnancy and motherhood. The ways in which information is framed in mHealth mirrors current gaps within sexual and reproductive health and rights, where a limited and conservative lens predominates, and which may result in narrow programming and implementation of services. PMID- 26278838 TI - From Project to Program: Tupange's Experience with Scaling Up Family Planning Interventions in Urban Kenya. AB - This paper describes how the Urban Reproductive Health Initiative in Kenya, the Tupange Project (2010-2015), successfully applied the ExpandNet approach to sustainably scale up family planning interventions, first in Machakos and Kakamega, and subsequently also in its three core cities, Nairobi, Kisumu and Mombasa. This new focus meant shifting from a "project" to a "program" approach, which required paying attention to government leadership and ownership, limiting external inputs, institutionalizing interventions in existing structures and emphasizing sustainability. The paper also highlights the project's efforts to prepare for the future scale up of Tupange's interventions in other counties to support continuing and improved access to family planning services in the new context of devolution (decentralization) in Kenya. PMID- 26278839 TI - "If a woman has even one daughter, I refuse to perform the abortion": Sex determination and safe abortion in India. AB - In India, safe abortion services are sought mainly in the private sector for reasons of privacy, confidentiality, and the absence of delays and coercion to use contraception. In recent years, the declining sex ratio has received much attention, and implementation of the Pre-Conception and Pre-Natal Diagnostic Techniques (PCPNDT) Act (2003) has become stringent. However, rather than targeting sex determination, many inspection visits target abortion services. This has led to many private medical practitioners facing negative media publicity, defamation and criminal charges. As a result, they have started turning women away not only in the second trimester but also in the first. Samyak, a Pune-based, non-governmental organization, came across a number of cases of refusal of abortion services during its work and decided to explore the experiences of private medical practitioners with the regulatory mechanisms and what happened to the women. The study showed that as a fallout from the manner of implementation of the PCPNDT Act, safe abortion services were either difficult for women to access or outright denied to them. There is an urgent need to recognize this impact of the current regulatory environment, which is forcing women towards illegal and unsafe abortions. PMID- 26278840 TI - From unwanted pregnancy to safe abortion: Sharing information about abortion in Asia through animation. AB - Although unsafe abortion continues to be a leading cause of maternal mortality in many countries in Asia, the right to safe abortion remains highly stigmatized across the region. The Asia Safe Abortion Partnership, a regional network advocating for safe abortion, produced an animated short film entitled From Unwanted Pregnancy to Safe Abortion to show in conferences, schools and meetings in order to share knowledge about the barriers to safe abortion in Asia and to facilitate conversations on the right to safe abortion. This paper describes the making of this film, its objectives, content, dissemination and how it has been used. Our experience highlights the advantages of using animated films in addressing highly politicized and sensitive issues like abortion. Animation helped to create powerful advocacy material that does not homogenize the experiences of women across a diverse region, and at the same time emphasize the need for joint activities that express solidarity. PMID- 26278841 TI - Using photovoice to examine community level barriers affecting maternal health in rural Wakiso district, Uganda. AB - Uganda continues to have poor maternal health indicators including a high maternal mortality ratio. This paper explores community level barriers affecting maternal health in rural Wakiso district, Uganda. Using photovoice, a community based participatory research approach, over a five-month period, ten young community members aged 18-29 years took photographs and analysed them, developing an understanding of the emerging issues and engaging in community dialogue on them. From the study, known health systems problems including inadequate transport, long distance to health facilities, long waiting times at facilities and poor quality of care were confirmed, but other aspects that needed to be addressed were also established. These included key gender-related determinants of maternal health, such as domestic violence, low contraceptive use and early teenage pregnancy, as well as problems of unclean water, poor sanitation and women's lack of income. Community members appreciated learning about the research findings precisely hence designing and implementing appropriate solutions to the problems identified because they could see photographs from their own local area. Photovoice's strength is in generating evidence by community members in ways that articulate their perspectives, support local action and allow direct communication with stakeholders. PMID- 26278842 TI - Statement on the 48th Session of the UN Commission on Population and Development, 27 April 2015. PMID- 26278843 TI - WHO Statement on caesarean section rates. PMID- 26278844 TI - Small bowel sarcoma: Tumor biology and advances in therapeutics. AB - Spindle cell neoplasms are rare mesenchymal tumors of the gastrointestinal tract. GIST (Gastrointestinal stromal tumor) and leiomyosarcoma share similar clinical presentations, gross and microscopic characteristics making distinction difficult in the absence of immunohistochemical (IHC) studies. A multidisciplinary approach is required for treatment planning and ensuring best outcomes. Surgery remains the mainstay of curative treatment for both tumors. Significant advances in targeted molecular therapies have occurred in the past decade in the treatment of GIST with improvement in morbidity and mortality. Similar newer discoveries for treatment of leiomyosarcoma have failed to show any significant survival benefits as yet. Early diagnosis and R0 surgical resection offers the best long term outcome for leiomyosarcoma. Here in we review and discuss the concepts of genetic alterations, newer markers, possible cancer pathways and advances in treatment strategies for these sarcomas. PMID- 26278845 TI - Seroprevalence of antibodies of Neospora spp. and Toxoplasma gondii in horses from southern Italy. AB - The consumption of horse meat has been epidemiologically linked to clinical toxoplasmosis in humans and neosporosis that may cause clinical illness in horses. Here we determined seroprevalence of antibodies against Toxoplasma gondii Nicolle et Manceaux, 1908 and species of Neospora Dubey, Carpenter, Speer, Topper et Uggla, 1988 in horses from Italy. Blood samples were collected from 643 apparently healthy horses from 60 farms of 51 municipalities in southern Italy. The presence of antibodies against T. gondii and Neospora spp. were detected by indirect fluorescence antibody test (IFAT); a titre >= 50 was considered positive. The same sera were also tested for antibodies against Neospora spp. by a competitive-inhibition enzyme-linked immunosorbent assay (cELISA); samples with >= 30% inhibition were considered positive. Antibodies against T. gondii and Neospora spp. were detected in 19 (3.0%) and 15 (2.3%) horses by IFAT, respectively, without statistical difference between gender, age and breeds (p value >= 0.05). Antibodies against species of Neospora were detected in 70 (10.9%) horses by cELISA with statistical difference in gender (6.0-18.5%, p value >= 0.05) and breeds (0-19.4%, p-value >= 0.05). Although T. gondii infection rates were low, the risk of human infection should not be dismissed, particularly in Italy where consumption of raw or undercooked horse meat has a long tradition. PMID- 26278846 TI - Vaginocervical stimulation attenuates the sensitization of appetitive sexual behaviors by estradiol benzoate in the ovariectomized rat. AB - The acute administration of estradiol benzoate (EB) to the ovariectomized (OVX) rat induces low levels of lordosis while sexually appetitive behaviors (e.g., hops, darts, solicitations) are absent, yet the repeated administration of EB results in a behavioral sensitization in which lordosis is potentiated and sexually appetitive behaviors are induced. We have shown that repeated copulation attenuates the sensitization of appetitive sexual behaviors. Here, we assessed which component of male stimulation during copulation is involved in the attenuation. On 8 occasions, sexually experienced OVX Long-Evans rats were treated with 10MUgEB and 48h later assigned to one of six groups that differed in their experience on intermediates tests (2-7). One was given repeated access to a male (EB/Male), and another was placed in the copulation chamber alone (EB/Alone) on intermediate tests. Three groups were given one of three somatosensory stimuli by the experimenter: manual flank stimulation (FLS), clitoral stimulation (CLS), or vaginocervical stimulation (VCS). Finally, the control group was left undisturbed in the animal care facility (ACF). Sexual behaviors were measured on Tests 1 and 8. VCS received from the experimenter (VCS) or from the male during copulation (EB/Male) attenuated the magnitude of the sensitization of appetitive sexual behaviors compared with those that were not brought to the testing rooms (ACF), and the effect was most pronounced on sexual solicitations. These results suggest that VCS received during penile intromission inhibits the sensitization of sexually appetitive behaviors by repeated administration of EB. As such, repeated administration of EB may oppose those mechanisms that induce estrous termination, perhaps by sensitizing inhibitory processes within the ventromedial hypothalamus that typically prevent the display of sexual behaviors (i.e., by facilitating disinhibition). PMID- 26278847 TI - Are stabilizing osmolytes preferentially excluded from the protein surface? FTIR and MD studies. AB - Interactions between osmolytes and hen egg white lysozyme in aqueous solutions were studied by means of FTIR spectroscopy and molecular dynamics. A combination of difference spectra method and chemometric analysis of spectroscopic data was used to determine the number of osmolyte molecules interacting with the protein, and the preferential interaction coefficient in presented systems. Both osmolytes -l-proline and trimethylamine-N-oxide (TMAO) - belong to a group of stabilizing osmolytes, and according to the preferential exclusion/hydration hypothesis, both should be excluded from the vicinity of the protein backbone and surface. We provide experimental and computational evidence that although TMAO behaves according to the hypothesis, proline does not. Our results suggest that preferential exclusion is not a universal property of stabilizing osmolytes. PMID- 26278848 TI - Letter From the Editors. PMID- 26278849 TI - Letter from the Guest Editor: Pitfalls and Limitations of Radionuclide and Hybrid Imaging--Part I. PMID- 26278850 TI - Pitfalls and Limitations of Radionuclide Planar and Hybrid Bone Imaging. AB - The radionuclide (99m)Tc-MDP bone scan is one of the most commonly performed nuclear medicine studies and helps in the diagnosis of different pathologies relating to the musculoskeletal system. With its increasing utility in clinical practice, it becomes more important to be aware of various limitations of this imaging modality to avoid false interpretation. It is necessary to be able to recognize various technical, radiopharmaceutical, and patient-related artifacts that can occur while carrying out a bone scan. Furthermore, several normal variations of tracer uptake may mimic pathology and should be interpreted cautiously. There is an important limitation of a bone scan in metastatic disease evaluation as the inherent mechanism of tracer uptake is not specific for tumor but primarily relies on an osteoblastic response. Thus, it is crucial to keep in mind uptake in benign lesions, which can resemble malignant pathologies. The utility of a planar bone scan in benign orthopedic diseases, especially at sites with complex anatomy, is limited owing to lack of precise anatomical information. SPECT/CT has been significantly helpful in these cases. With wider use of PET/CT and reintroduction of the (18)F-fluoride bone scan, increasing knowledge of potential pitfalls on an (18)F-fluoride bone scan and (18)F-FDG-PET/CT will help in improving the accuracy of clinical reports. PMID- 26278851 TI - Artifacts and Anatomical Variants Affecting Ventilation and Perfusion Lung Imaging. AB - Ventilation and perfusion lung imaging continues to be an important technique in the investigation of lung disease, particularly pulmonary emboli. For the most accurate interpretation, a solid understanding of the agents available, underlying physiology, and normal variants is required. A number of ventilation agents are available ranging from true gases to aqueous aerosols and carbon nanoparticles. The addition in recent years of SPECT imaging, although improving the technique, has added to the range of artifacts and variants to be appreciated. In addition, there are uncommon conditions that can affect the scan appearance. A selection of these variants and artifacts is discussed in this article. PMID- 26278852 TI - Pitfalls and Limitations of Radionuclide and Hybrid Cardiac Imaging. AB - Radionuclide myocardial perfusion imaging (MPI) is an important technique for evaluating the presence and severity of ischemic coronary heart disease that is widespread in the United States and much of the world. This widely used test has excellent diagnostic accuracy and strong risk-stratification utility and plays an important role in guiding patient management. As with all testing modalities, the clinical utility of MPI relies on proper procedure performance as improper techniques can lead to incorrect test interpretation, and thus misdiagnosis with potential adverse effects on patient management and outcome. A variety of potential pitfalls must be understood and recognized. These include minimizing referral of "rarely appropriate" patients for testing, selecting the best imaging procedure for each patient, properly preparing a patient for the test to be performed, skillful performance of stress testing and image acquisition, careful image processing, understanding the strengths and weaknesses of different image display options, recognition of common artifacts that can lead to misdiagnoses, distinguishing normal anatomy from true pathology, recognizing noncoronary cardiac disease, and not missing extracardiac pathology. It is important that physicians who perform and interpret radionuclide MPI be well versed in published guidelines and potential pitfalls to proper test performance and interpretation. PMID- 26278853 TI - Pitfalls and Limitations of Radionuclide Renal Imaging in Pediatrics. AB - The article presents common pitfalls encountered in pediatric radionuclide renography, illustrated with clinical cases. It is important to recognize normal variants. A good acquisition technique is essential. Correlation with other imaging techniques, with the clinical background and symptoms, is critical. A clear clinical question is essential: based on the question and knowing the strengths and weaknesses of each test, the test which can best answer the question can be selected. Awareness of the pitfalls of radionuclide renography helps avoid errors of interpretation and allows the selection of the most helpful test for clinical management. PMID- 26278854 TI - Pitfalls and Limitations of Radionuclide Renal Imaging in Adults. AB - To understand pitfalls and limitations in adult renography, it is necessary to understand firstly the physiology of the kidney, especially the magnitude and control of renal blood flow, glomerular filtration rate and tubular fluid flow rate, and secondly the pharmacokinetics and renal handling of the three most often used tracers, Tc-99m-mercaptoacetyltriglycine (MAG3), Tc-99m-diethylene triamine pentaacetic acid (DTPA) and Tc-99m-dimercaptosuccinic acid (DMSA). The kidneys may be imaged dynamically with Tc-99m-MAG3 or Tc-99m-DTPA, with or without diuretic challenge, or by static imaging with Tc-99m-DMSA. Protocols are different according to whether the kidney is native or transplanted. Quantitative analysis of dynamic data includes measurement of renal vascularity (important for the transplanted kidney), absolute tracer clearance rates, differential renal function (DRF) and response to diuretic challenge. Static image reveals functional renal parenchymal damage, both focal and global, is useful in the clinical management of obstructive uropathy, renal stone disease and hypertension (under angiotensin converting enzyme inhibition), and is the preferred technique for determining DRF. Diagnosis based on morphological appearances is important in transplant management. Even though nuclear medicine is now in the era of hybrid imaging, renal imaging remains an important subspecialty in nuclear medicine and requires a sound basing in applied physiology, the classical supporting discipline of nuclear medicine. PMID- 26278855 TI - Pitfalls and Limitations of Radionuclide Imaging in Endocrinology. AB - Several different techniques, radiopharmaceuticals, and imaging modalities are commonly used in nuclear medicine for studies of endocrine organs. Nuclear medicine is used in the management of benign and malignant thyroid, parathyroid, and neuroendocrine disorders. Thus, it is essential to acknowledge pitfalls and the limitations of nuclear medicine imaging for accurate diagnosis and patient management. PMID- 26278856 TI - Artifacts and Incidental Findings Encountered on Dual-Energy X-Ray Absorptiometry: Atlas and Analysis. AB - Bone mineral densitometry (BMD) using dual-energy x-ray absorptiometry (DEXA) has been widely adopted as the standard method of assessing bone density. Although not intended to be a primary imaging modality, the technique generates attenuation map images that are used to guide region-of-interest placement. Artifacts and incidental findings are frequently encountered on the DEXA images, some of which directly affect BMD values and others that are only of incidental importance to clinical practice. We systematically review a variety of artifacts and incidental findings that may be encountered on DEXA, illustrated by a collection of findings from our own practice. Being cognizant of these unexpected abnormalities, and understanding their etiology, will prepare the reader to more readily appreciate significance of these findings when seen in clinical practice. PMID- 26278857 TI - Pitfalls and Limitations of SPECT, PET, and Therapeutic Radiopharmaceuticals. AB - Radiopharmaceuticals are widely accepted to be a very safe class of drugs, with very few adverse reactions and unexpected biodistributions. However, problems can arise because of technical issues in manufacture or reconstitution, patient preparation, or drug administration. This review presents highlights of issues that have arisen in the newer classes of radiopharmaceuticals in the last 20 years and expands the scope of the previous report to include PET and therapeutic radiopharmaceuticals. Variations in the "quality" of the eluate of a (99)Mo/(99m)Tc generator remain a major issue. Several of the newer (99m)Tc tracers require a heating step in preparation that can also lead to unacceptably low radiochemical purity. Radiolytic breakdown can be a problem with all classes of radiopharmaceuticals. Many of the newer radiopharmaceuticals localize by receptor- or transporter-mediated processes and thus can be affected by other drugs, making patient preparation more important than ever. Therapeutic radiopharmaceuticals may require coadministration of radioprotectant regimens, such as the use of lysine-arginine infusions with radiopeptide therapy. Extravasation can have serious consequences with therapeutic radiopharmaceuticals. Adverse reactions to newer radiopharmaceuticals remain rare, though may increase because of coadministration of agents such as contrast media. However, there is known to be underreporting of minor adverse reactions. Knowledge of the pitfalls that can occur with radiopharmaceuticals is important in the interpretation of nuclear medicine images and optimal patient care. PMID- 26278858 TI - Atopic Keratoconjunctivitis in Children: Clinical Features and Diagnosis. PMID- 26278859 TI - Incidence, Risk Factors, and Impact of Age on Retinal Detachment after Cataract Surgery in France: A National Population Study. AB - PURPOSE: To assess the incidence, risk factors, and impact of age on retinal detachment (RD) after cataract surgery. DESIGN: Cohort study. PARTICIPANTS: All patients older than 40 years of age who underwent a primary cataract surgery in France between January 2009 and December 2012. METHODS: A Cox proportional-hazard regression model was used to analyze risk factors of RD after cataract surgery. MAIN OUTCOME MEASURES: Risk factors of RD after cataract surgery. RESULTS: Over 4 years, 2680167 eyes in 1787021 patients (59.4% women; mean age, 73.9+/-9.5 years) underwent cataract surgery. A total of 11 424 patients experienced RD after cataract surgery, with an estimated risk of 0.99% at 4 years after surgery. The odds ratio associated with increased risk of RD was 3.87 (95% confidence interval [CI], 3.79-3.95) for cataract surgery itself. The multiadjusted hazard ratio (HR) associated with increased risk of RD was 5.22 (95% CI, 5.05-5.39) for patients 40 to 54 years of age, 3.69 (95% CI, 3.60-3.79) for those 55 to 64 years of age, and 1.98 (95% CI, 1.93-2.03) for those 65 to 74 years of age as compared with those 75 years of age or older. Retinal detachment was associated with high myopia (HR, 6.12; 95% CI, 5.84-6.41), vitrectomy for perioperative capsular rupture (HR, 4.36; 95% CI, 4.07-4.68), history of eye trauma (HR, 3.98; 95% CI, 3.69-4.30), extracapsular extraction (HR, 3.11; 95% CI, 2.94-3.30), male gender (HR, 2.39; 95% CI, 2.35-2.44), and history of diabetes (HR, 1.18; 95% CI, 1.15-1.21). In myopic patients, the multiadjusted HR associated with increased risk of RD was 25.02 (95% CI, 24.76-25.18) for patients 40 to 54 years of age, 20.37 (95% CI, 20.21-20.53) for those 55 to 64 years of age, and 17.05 (95% CI, 16.85-17.25) for those 65 to 74 years of age as compared with nonmyopic patients 75 years of age or older. CONCLUSIONS: We provide a hierarchy of risk factors for RD onset: high myopia, young age, capsular rupture, history of eye trauma, extracapsular extraction technique, male gender, and diabetes. Young age was an additional risk factor in myopic patients. PMID- 26278860 TI - Automated Detection of Hemifield Difference across Horizontal Raphe on Ganglion Cell--Inner Plexiform Layer Thickness Map. AB - PURPOSE: A MATLAB-based (The MathWorks, Inc, Natick, MA) computer program (the ganglion cell-inner plexiform layer [GCIPL] hemifield test) for automated detection of GCIPL thickness difference across the horizontal raphe was developed, and its glaucoma diagnostic performance was assessed. DESIGN: Cross sectional study. PARTICIPANTS: A total of 65 eyes of normal, healthy subjects along with 162 eyes of patients with glaucoma (79 preperimetric and 83 early perimetric). METHODS: Cirrus high-definition optical coherence tomography (HD OCT) (Carl Zeiss Meditec, Dublin, CA) was used to scan all of the subjects' macular and optic discs. A positive (i.e., "outside normal limits") GCIPL hemifield test result was declared if the following 3 conditions were all met: (1) The reference line (a horizontal line dividing the superior and inferior hemifields) is continuously detected for longer than one-half of the distance from the temporal inner elliptical annulus to the outer elliptical annulus; (2) the average GCIPL thickness difference within 10 pixels of the reference line, both above and below, is >=5 MUm; and (3) the average RGB color ranges of the 10 pixels above and below the reference line display blue in 1 hemifield and red/yellow/white in the other hemifield. MAIN OUTCOME MEASURES: Comparison of diagnostic ability using the areas under the receiver operating characteristic curves (AUCs). RESULTS: A positive GCIPL hemifield test result was observed more frequently in the glaucomatous eyes (74/79 preperimetric, 78/83 early perimetric) than in the normal eyes (1/65). In the preperimetric group, the AUC of the GCIPL hemifield test (0.967; sensitivity 94.94%, specificity 98.46%) was greater than that of the minimum GCIPL thickness (0.933), the inferotemporal GCIPL thickness (0.907), and the average GCIPL thickness (0.899) (P=0.09, 0.06, and 0.03, respectively). In the early perimetric group, the AUC of the GCIPL hemifield test (0.962; sensitivity 93.98%, specificity 96.46%) was greater than that of the inferotemporal GCIPL thickness (0.938), the minimum GCIPL thickness (0.919), and the average GCIPL thickness (0.912) (P=0.38, 0.17, and 0.11, respectively). CONCLUSIONS: For discrimination of early glaucomatous structural loss, most notably in preperimetric glaucoma cases, identification of the GCIPL thickness difference across the horizontal raphe was effective. PMID- 26278861 TI - Prevalence of Amblyopia in School-Aged Children and Variations by Age, Gender, and Ethnicity in a Multi-Country Refractive Error Study. AB - PURPOSE: To estimate the age-, gender-, and ethnicity-specific prevalence of amblyopia in children aged 5 to 15 years using data from the multi-country Refractive Error Study in Children (RESC). DESIGN: Population-based, cross sectional study. PARTICIPANTS: Among 46 260 children aged 5 to 15 years who were enumerated from 8 sites in the RESC study, 39 551 had a detailed ocular examination and a reliable visual acuity (VA) measurement in 1 or both eyes. Information on ethnicity was available for 39 321 of these participants. This study focused on findings from the 39 321 children. METHODS: The examination included VA measurements, evaluation of ocular alignment and refractive error under cycloplegia, and examination of the external eye, anterior segment, media, and fundus. MAIN OUTCOME MEASURES: The proportion of children aged 5 to 15 years with amblyopia in different ethnic cohorts. Amblyopia was defined as best corrected visual acuity (BCVA) of <=20/40 in either eye, with tropia, anisometropia (>=2 spherical equivalent diopters [D]), or hyperopia (>=+6 spherical equivalent D), after excluding children with fundus or anterior segment abnormalities. RESULTS: The overall prevalence of amblyopia was 0.74% (95% confidence interval, 0.64-0.83) with significant (P < 0.001) variation across ethnic groups: 1.43% in Hispanic, 0.93% in Chinese, 0.62% in Indian, 0.52% in Malay, 0.35% in Nepali, and 0.28% in African children. Amblyopia was not associated with age or gender. The most common cause of amblyopia was anisometropia. CONCLUSIONS: In this study, the prevalence of amblyopia varied with ethnicity and was highest in Hispanic children and lowest in African children. Most cases were unilateral and developed before the age of 5 years. The impact of changes of definitions on prevalence estimates is discussed. PMID- 26278862 TI - High Prevalence of Untreated Depression in Patients Accessing Low-Vision Services. PMID- 26278863 TI - Effect of Prior Anti-VEGF Injections on the Risk of Retained Lens Fragments and Endophthalmitis after Cataract Surgery in the Elderly. AB - PURPOSE: To investigate the effect of prior intravitreal anti-vascular endothelial growth factor (VEGF) injections on surgical and postoperative complication rates associated with cataract surgery in a nationally representative longitudinal sample of elderly persons. DESIGN: Retrospective, longitudinal cohort analysis. PARTICIPANTS: A total of 203 643 Medicare beneficiaries who underwent cataract surgery from January 1, 2009, to December 31, 2013. METHODS: By using the 5% sample of Medicare claims data, the study assessed risks of 3 adverse outcomes after receipt of cataract surgery for beneficiaries with a history of intravitreal injections. Risks of these outcomes in beneficiaries with a history of intravitreal injections relative to those without were calculated using the Cox proportional hazard model. MAIN OUTCOME MEASURES: The primary outcome was the risk of subsequent removal of retained lens fragments (RLFs) within 28 days after cataract surgery. Secondary outcomes were a new diagnosis of acute (<40 days) or delayed-onset (40+ days) endophthalmitis and risk of a new primary open-angle glaucoma (POAG) diagnosis within 365 days after cataract surgery. RESULTS: Prior intravitreal anti-VEGF injections were associated with a significantly increased risk of subsequent RLF removal within 28 days after cataract surgery (hazard ratio [HR], 2.26; 95% confidence interval [CI], 1.19-4.30). Prior injections were also associated with increased risk of both acute (HR, 2.29; 95% CI, 1.001-5.22) and delayed-onset endophthalmitis (HR, 3.65; 95% CI, 1.65-8.05). Prior injections were not a significant indicator of increased risk of a new POAG diagnosis. CONCLUSIONS: A history of intravitreal injections may be a risk factor for cataract surgery-related intraoperative complications and endophthalmitis. Given the frequency of intravitreal injections and cataract surgery, increased preoperative assessment, additional intraoperative caution, and postoperative vigilance are recommended in patients with a history of intravitreal injections undergoing cataract extraction. PMID- 26278864 TI - Utility of Preoperative Magnetic Resonance Imaging Coregistered with Intraoperative Computed Tomographic Scan for the Resection of Complex Tumors of the Spine. AB - BACKGROUND: Complete surgical resection is known to provide the best prognosis when treating complex tumors of the spine. The anatomy of the cervical spine and the extensive involvement often present by the time these lesions are discovered can make total resection challenging. A novel technique combining preoperative and intraoperative imaging for intraoperative navigation can serve as an additional tool for facilitating tumor resection. METHODS: Preoperative MRI was coregistered with intraoperative CT for accurate, real-time, intraoperative navigation for complete resection of complex tumors of the cervical spine. This new technique is demonstrated. The potential advantages and challenges are discussed. RESULTS: Preoperative MRI coregistered and merged with intraoperative CT allows for accurate visualization of tumor boundaries, osseous anatomy, and surrounding soft tissue structures. Total resection of extensive spinal tumors involving the anterior and posterior elements can be facilitated with this technique. CONCLUSIONS: Preoperative MRI coregistered and merged with intraoperative CT may serve as a useful intraoperative imaging modality for facilitating safe and complete resection of complex spine tumors. PMID- 26278865 TI - Rational Approach to Understanding and Preventing Sports-Related Traumatic Brain Injuries. PMID- 26278866 TI - Mass Effect Due to Hypertrophic Pericranial Flap in the Reconstruction of Dural Defect. AB - OBJECTIVE: To present a case of symptomatic mass effect caused by engorgement of a vascularized pericranial flap in the repair of dural defect secondary to parasagittal meningioma surgical excision, in order to expose a potential complication from this reconstruction technique. CASE: A 62-year-old man with a left medial-third type 1 of Sindou's classification parasagittal meningioma underwent complete Simpson 1 surgical excision. For the reconstruction of the dural defect, a vascularized pericranial flap was sutured using water-sealed technique. On postsurgical day 2, the patient developed progressive neurologic impairment characterized by stupor. Magnetic resonance imaging stroke sequence revealed what appears to be an extradural collection not visualized on an immediate postsurgical computed tomographic scan. In surgical reexploration, we found an engorged pericranial flap causing direct compression to the parenchyma without the presence of additional hematoma in the surgical field. RESOLUTION: The pericranial flap needed to be excised, and the dural defect was repaired using synthetic material. No permanent neurologic deficit was documented at 6 month follow-up. CONCLUSION: We hypothesized that pericranial flap was strangulated because of final bone flap replacement so that venous outflow was compromised. This complication can be prevented if adequate drilling of the inner table at the edge of the craniotomy and at the outer table of the bone flap is performed just at the entry zone of pericranium flap pedicle to avoid a 90 degrees angle of entry resulting in vascular congestion. PMID- 26278867 TI - Neurosurgical Care for One--Neurosurgical Care for All: Global Neurosurgical Care Has Global Benefits! PMID- 26278868 TI - Effects of Clot Removal by Meticulous Irrigation and Continuous Low-Dose Intravenous Nicardipine on Symptomatic Cerebral Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage Treated by Clipping. AB - BACKGROUND: Symptomatic cerebral vasospasm (SCV) is the second most common of morbidity and mortality in aneurysmal subarachnoid hemorrhage (aSAH) after rebleeding. Blood breakdown products are one of the leading causes of vasospasm. We hypothesized that meticulous subarachnoid clot removal in addition to continuous low-dose intravenous nicardipine (CLIN) could reduce the incidence of SCV. METHODS: SCV was defined as new focal neurologic signs, consciousness deterioration, or both when the cause was believed to be ischemia attributable to vasospasm after other possible causes of worsening were excluded. Initial brain damage was defined as continued consciousness disturbance after clipping without acute hydrocephalus, ischemic lesions, or focal sign before clipping. Poor outcome was defined as a Glasgow Outcome Scale score of 3-5 at 30 days. We compared the variables for 460 aSAH patients with and without SCV, and with and without poor outcome by multivariate analysis. RESULTS: All patients underwent clipping with meticulous irrigation for clot removal, and SCV was observed in 56 patients (12%). SCV was observed in 2 patients (2.9%) among 70 patients treated with CLIN. There was a higher proportion of patients who were older than 65 years (P = 0.032) and female (P = 0.038), and a lower proportion of patients with CLIN (P = 0.026) among patients with SCV. The outcomes for 109 patients (27%) were poor; age greater than 65 years (P < 0.0001) and initial brain damage (P = 0.008) were related to the poor outcomes. CONCLUSIONS: The present study showed that meticulous irrigation for clot removal and CLIN might reduce the incidence of SCV in patients with aSAH. PMID- 26278869 TI - Thinking from the Heart: Neurocristopathy, Aortic Abnormalities, and Intracranial Aneurysms. PMID- 26278870 TI - Role of Endoscopic Third Ventriculostomy in the Management of Myelomeningocele Related Hydrocephalus: A Retrospective Study in a Single French Institution. AB - INTRODUCTION: Treatment of hydrocephalus related to myelomeningocele (MM) is debated. Endoscopic third ventriculostomy (ETV) has been proposed with contrasting results. We report our experience in the management of hydrocephalus related to MM and the advantages of ETV. MATERIAL AND METHODS: From 1994 to 2012, we treated 97 patients with MM. Seventy patients developed a hydrocephalus needing a surgical treatment. Three types of procedures were used: ETV with concomitant choroid plexus coagulation (CPC), ETV with concomitant ventriculoperitoneal shunt (VPS), or VPS. RESULTS: Thirty-two patients had an ETV with CPC, 20 patients had an ETV and a concomitant VPS, and 18 patients had a VPS. No perioperative complications were reported. Fifty-two patients underwent an ETV. The overall success rate of ETV was approximately 70%. DISCUSSION: VPS in patients with MM leads to complications. Two common arguments are reported against ETV. The first is the variability of the anatomy of the ventricle leading to possible operative complications. The second is the immaturity of the Pacchioni granulations. For us, the modified anatomy does not prevent performing ETV. Regarding the issue of cerebrospinal fluid absorption in failed ETV, the adjunction of a shunt helps to control hydrocephalus until the maturation of the Pacchioni system. CONCLUSIONS: Preoperative imaging helps the surgical decision to predict in which patients the ETV can be realized without risks. ETV in patients with MM is a secure procedure with low rates of failure and no mortality, and it reduces the rate of shunt implantation. PMID- 26278871 TI - Chemosensory impairment does not diminish eating pleasure and appetite in independently living older adults. AB - OBJECTIVE: This study aims to evaluate the impact of chemosensory impairment on diminished eating pleasure and appetite in independently living Italian older adults. STUDY DESIGN: 239 individuals (65 to 101 years old, 157 women), with no severe medical conditions and good cognitive performance were recruited. Olfactory and gustatory functions were measured using a short version of Sniffin' Sticks and Taste Strips tests (Burghart). Information about socio-demographic characteristics, health, perceived smell and taste impairment, diminished eating pleasure and appetite were obtained with a specially designed questionnaire. RESULTS: Prevalence of chemosensory impairment detected in this sample is high, being 41% for taste and 33% for olfaction. However, the frequency of self reported impairment is consistently lower than the measured one, especially in men and in older subjects. Measured chemosensory impairment is not significantly related with eating pleasure and appetite. On the other hand, factors significantly influencing decline of eating pleasure are: living alone, dietary restriction and perceived taste impairment. Meanwhile, a significant influence of dietary restriction, dentures and subjective health status on appetite decline is observed. CONCLUSIONS: The results of this study show that chemosensory impairment may not be related with diminished eating pleasure and appetite, while other non-physiological factors such as loneliness, dietary restrictions and subjective health should be taken more into account in order to develop effective strategies to counteract malnutrition in the elderly. In addition, low awareness of chemosensory impairment among this sample highlights the importance of measuring sensory acuity rather than asking by questionnaire or interview, in order to obtain reliable data. PMID- 26278872 TI - Tooth loss and bone mineral density in postmenopausal South Korean women: The 2008-2010 Korea National Health and Nutrition Examination Survey. AB - PURPOSE: The current study aimed to investigate the association between the number of remaining teeth and bone mineral density (BMD) using data from the Korean National Health and Nutrition Examination Survey (KNHANES) 2008-2010. METHODS: This study enrolled 7315 Korean subjects (3364 men over 50 years of age and 3951 postmenopausal women). BMD was measured using dual-energy X-ray absorptiometry at three sites: the total femur (TF), femur neck (FN), and lumbar spine (LS). The number of teeth present was categorized into four groups (<=10, 11-20, 21-25, and >=26 teeth). RESULTS: More remaining teeth were significantly associated with a higher BMD at the TF, FN, and LS in postmenopausal women after adjusting for all the covariates, but not in elderly men. In both sexes, subjects with a normal BMD tended to have more remaining teeth than those who were diagnosed with osteopenia and osteoporosis. A lower prevalence of osteoporosis was also significantly associated with more remaining teeth (number of teeth >=26) in postmenopausal women. This trend was statistically significant in osteoporosis at the FN (p for trend=0.019). CONCLUSION: The number of remaining teeth was associated with osteoporosis, especially at the FN, in postmenopausal women. PMID- 26278873 TI - Menopause prediction and potential implications. AB - Reproductive ageing in women is characterized by a decline in both the quantity and quality of oocytes. Menopause is reached upon exhaustion of the resting primordial follicle pool, occurring on average at 51 years of age (range 40-60 years). The mean global age at natural menopause (ANM) appears robust, suggesting a distinct genetic control. Accordingly, a strong correlation in ANM is observed between mothers and daughters. Few specific genetic determinants of ANM have been identified. Substantial efforts have been made to predict ANM by using anti Mullerian hormone (AMH) levels. AMH serum concentrations at reproductive age predict ANM, but precision is currently limited. Early ANM is associated with early preceding fertility loss, whereas late menopause is associated with reduced morbidity and mortality later in life. Menopause affects various women's health aspects, including bone density, breast, the cardiovascular system, mood/cognitive function and sexual well-being. If the current trend of increasing human life expectancy persists, women will soon spend half their life postmenopause. Unfortunately, increased longevity does not coincide with an equal increase in years spend in good health. Future research should focus on determinants of long term health effects of ANM, and efforts to improve women's postmenopausal health and quality of life. PMID- 26278874 TI - The controversial existence and functional potential of oogonial stem cells. AB - The regenerative potential of the mammalian ovary has been a controversial area over the last decade. Isolation of cells, termed oogonial stem cells (OSCs), from adult rodent and human ovaries has been reported, with these cells exhibiting both germ and stem cell markers in culture. When re-introduced into an ovarian somatic environment these cells have generated follicles capable of producing healthy offspring in rodents, and there is some evidence of human OSCs being able to form oocyte-like structures in a xenotransplant model. Importantly, there are no data on their potential physiological role within the ovary, and specifically no evidence that they contribute to the primordial follicle pool and thus to later stages of follicle development. The cues required for oocyte differentiation from these cells are not well understood either in vivo or in vitro, and these will need to be further elucidated to maximise their potential for therapeutic intervention. OSCs may also be of value as a model to investigate normal human germ cell differentiation. It is likely that their interactions with ovarian somatic cells and/or extracellular signals will be important in these processes. This review summarises our current knowledge on the isolation and characterisation of mammalian oogonial stem cells. PMID- 26278875 TI - Does better for the environment mean less tasty? Offering more climate-friendly meals is good for the environment and customer satisfaction. AB - Food consumption comprises a significant portion of the total environmental impact of households. One way to reduce this impact may be to offer consumers more climate-friendly meal choices, such as when eating out. However, the environmental benefits of such an intervention will depend on not only consumers' liking of the climate-friendlier meals, but also on the perceived environmental impact. We therefore investigated the relationship between the global warming potential (GWP) of and consumers' liking of meals in two field studies in the same restaurant. Visitors to the restaurant were asked to rate the taste of the meal they had just consumed. These taste ratings were then related to the meals' GWP and number of purchases. In the second study, an intervention was tested consisting of a climate-friendly choice label and information posters. Contrary to expectations, it was found in both studies that the GWP of the meals was unrelated to the taste or the number of purchases. Offering more climate-friendly meals did not change consumer satisfaction. As expected, the introduction of the climate-friendly choice label increased the number of climate-friendly meal purchases. Therefore, offering more climate-friendly meals with a climate friendly choice label can affect consumers' meal choices, but not their preferences or satisfaction, which is beneficial for the climate, consumers and gastronomic establishments. PMID- 26278876 TI - Potential problems with increasing serving sizes on the Nutrition Facts label. AB - The United States Food and Drug Administration recently announced that the serving sizes on the Nutrition Facts labels for many products will be increased, but the effect of these increases remains unclear. The present research examined consumers' interpretation of the meaning of serving size information (study 1) and tested whether exposing consumers to the increased serving sizes of the proposed Nutrition Facts label leads consumers to serve and purchase more food for themselves and others (studies 2-4). Study 1 (N = 101; 44.7% female) tested what consumers believe the serving sizes on Nutrition Facts labels refer to, and the majority of participants (over 78%) incorrectly believed that the serving sizes refer to how much food can or should be consumed in one sitting as part of a healthy diet. Study 2 (N = 51; 41.2% female) tested how exposure to the current versus proposed Nutrition Facts label influences the amount of food that consumers serve themselves, and studies 3 (N = 60; 46.7% female) and 4 (N = 61; 48.2% female) assessed how exposure to the current versus proposed label influences the amount of food that people serve and purchase for others. In studies 2-4, the proposed label (vs. the current label) led consumers to serve themselves 41% more cookies (study 2); serve 27% more cheese crackers to another person (study 3); and buy 43% more lasagnas for others and divide a lasagna into 22% larger slices (study 4). The results suggest that the proposed Nutrition Facts label's increased serving sizes may lead people who use this information as a reference to serve more food to themselves and others. PMID- 26278877 TI - Rectal cancer patients after neoadjuvant radiotherapy (30Gy/10f) with negative lymph node may not benefit from postoperative adjuvant chemotherapy: a retrospective study. AB - OBJECTIVE: The purpose of this study is to evaluate whether adjuvant chemotherapy could bring oncologic benefit to all patients who underwent neoadjuvant radiotherapy (30Gy/10f). METHODS: Rectal cancer patients receiving preoperative radiotherapy between July 2002 and April 2009 were retrospectively identified. RESULTS: A total of 225 patients were enrolled in this study. One hundred thirty one patients received postoperative adjuvant chemotherapy, and 94 patients did not. The 120 ypN+ and 105 ypN- patients were divided into chemo and non-chemo groups. Two groups of patients did not show any significant difference in terms of gender, age, ypT stage, preoperative serum carcinoembryonic antigen (CEA) level, differentiation, circumferential margin (CRM), lymphovascular invasion (LVI), surgical approach, local recurrence, and distant metastasis (P > 0.05). Survival analysis showed that in ypN+ patients, the 5-year overall survival (OS) rate and 5-year disease-free survival (DFS) rate in chemo group were both significantly higher than non-chemo group (P < 0.05). In ypN- patients, the 5 year OS rate and 5-year DFS rate did not show any significant difference in the two groups (P > 0.05). Subgroup analysis showed that the 5-year OS rate and 5 year DFS rate in ypT0-2 N- patients (P > 0.05) and ypT3-4 N- patients (P > 0.05) did not show any significant difference, either. CONCLUSIONS: Based on a Chinese protocol, patients with ypN- stage may not benefit from adjuvant chemotherapy, regardless of the ypT stage, while the ypN+ patients may benefit from adjuvant chemotherapy. More randomized clinical trials are needed in the future. PMID- 26278878 TI - Impact of sphincter invasion on T stage definition in rectal cancer. PMID- 26278879 TI - Magnet compression technique: a novel method for rectovaginal fistula repair. PMID- 26278880 TI - Morphometrics and levels of infections of digeneans in belonid fish species off the coast of Tunisia. AB - Three species of belonid fish, Belone belone gracilis Lowe, 1839, Belone svetovidovi Collette & Parin, 1970 and Tylosurus acus imperialis (Rafinesque, 1810), caught off the eastern Tunisian coast were infected with eight species of Digenea. Among these, four species were commonly found in B. b. gracilis and are new host records for B. svetovidovi. They are: Lecithostaphylus retroflexus (Molin, 1859), Tergestia acanthocephala (Stossich, 1887) Stossich, 1899 and Aponurus laguncula Looss, 1907 in the intestine, and the metacercaria Condylocotyla pilodora Pearson and Prevot, 1985 in the pericardial sac. Four other digenean species were recorded from T. a. imperialis: Lecithostaphylus tylosuri Chaari et al., 2013 and Tetrochetus coryphaenae Yamaguti, 1934 in the intestine, Oesophagotrema mediterranea Chaari et al., 2011 in the oesophagus and vomer teeth, and Sclerodistomoides pacificus Kamegai, 1971 in the gall bladder. Tetrochetus coryphaenae and S. pacificus represent new host and geographical records. The spatial variation of digenean parasites within belonid host species is discussed. PMID- 26278881 TI - Stepped wedge randomised controlled trials: systematic review of studies published between 2010 and 2014. AB - BACKGROUND: In a stepped wedge, cluster randomised trial, clusters receive the intervention at different time points, and the order in which they received it is randomised. Previous systematic reviews of stepped wedge trials have documented a steady rise in their use between 1987 and 2010, which was attributed to the design's perceived logistical and analytical advantages. However, the interventions included in these systematic reviews were often poorly reported and did not adequately describe the analysis and/or methodology used. Since 2010, a number of additional stepped wedge trials have been published. This article aims to update previous systematic reviews, and consider what interventions were tested and the rationale given for using a stepped wedge design. METHODS: We searched PubMed, PsychINFO, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Web of Science, the Cochrane Library and the Current Controlled Trials Register for articles published between January 2010 and May 2014. We considered stepped wedge randomised controlled trials in all fields of research. We independently extracted data from retrieved articles and reviewed them. Interventions were then coded using the functions specified by the Behaviour Change Wheel, and for behaviour change techniques using a validated taxonomy. RESULTS: Our review identified 37 stepped wedge trials, reported in 10 articles presenting trial results, one conference abstract, 21 protocol or study design articles and five trial registrations. These were mostly conducted in developed countries (n = 30), and within healthcare organisations (n = 28). A total of 33 of the interventions were educationally based, with the most commonly used behaviour change techniques being 'instruction on how to perform a behaviour' (n = 32) and 'persuasive source' (n = 25). Authors gave a wide range of reasons for the use of the stepped wedge trial design, including ethical considerations, logistical, financial and methodological. The adequacy of reporting varied across studies: many did not provide sufficient detail regarding the methodology or calculation of the required sample size. CONCLUSIONS: The popularity of stepped wedge trials has increased since 2010, predominantly in high-income countries. However, there is a need for further guidance on their reporting and analysis. PMID- 26278883 TI - Diffusive dynamics of nanoparticles in ultra-confined media. AB - Differential dynamic microscopy (DDM) was used to investigate the diffusive dynamics of nanoparticles of diameter 200-400 nm that were strongly confined in a periodic square array of cylindrical nanoposts. The minimum distance between posts was 1.3-5 times the diameter of the nanoparticles. The image structure functions obtained from the DDM analysis were isotropic and could be fit by a stretched exponential function. The relaxation time scaled diffusively across the range of wave vectors studied, and the corresponding scalar diffusivities decreased monotonically with increased confinement. The decrease in diffusivity could be described by models for hindered diffusion that accounted for steric restrictions and hydrodynamic interactions. The stretching exponent decreased linearly as the nanoparticles were increasingly confined by the posts. Together, these results are consistent with a picture in which strongly confined nanoparticles experience a heterogeneous spatial environment arising from hydrodynamics and volume exclusion on time scales comparable to cage escape, leading to multiple relaxation processes and Fickian but non-Gaussian diffusive dynamics. PMID- 26278882 TI - Ab initio and density functional theory calculations of molecular structure and vibrational spectra of 4-(2-Hydroxyethyl) piperazine-1-ethanesulfonic acid. AB - The FTIR and FT-Raman spectra of 4-(2-Hydroxyethyl) piperazine-1-ethanesulfonic acid were recorded and the structural and spectroscopic data of the molecule in the ground state were calculated using Hartree-Fock and Density Functional Method (B3LYP). The most stable conformer was optimized and the structural and vibrational parameters were determined. With the observed FTIR and FT-Raman data, a complete vibrational band assignment and analysis of the fundamental modes of the compound were carried out. Thermodynamic properties, Mulliken and natural atomic charge distribution were calculated using both Hartree-Fock and Density Functional Method and compared. UV-Visible and HOMO-LUMO analysis were carried out. (1)H and (13)C NMR chemical shifts of the molecule were calculated using gauge including atomic orbital method and were compared with experimental results. Stability of the molecule arising from hyperconjugative interactions and charge delocalization has been analyzed using natural bond orbital analysis. The first order hyperpolarizability (beta) and molecular electrostatic potential of the molecule was computed using DFT calculations. The electron density based local reactivity descriptor such as Fukui functions were calculated to explain the chemically reactive site in the molecule. PMID- 26278884 TI - Carbohydrate nanocarriers in biomedical applications: functionalization and construction. AB - The specific targeting of either tumor cells or immune cells in vivo by carefully designed and appropriately surface-functionalized nanocarriers may become an effective therapeutic treatment for a variety of diseases. Carbohydrates, which are prominent biomolecules, have shown their outstanding ability in balancing the biocompatibility, stability, biodegradability, and functionality of nanocarriers. The recent applications of sugar (mono/oligosaccharides and/or polysaccharides) for the development of nanomedicines are summarized in this review, including the application of carbohydrates for the surface-functionalization of various nanocarriers and for the construction of the nanocarrier itself. Current problems and challenges are also addressed. PMID- 26278885 TI - Regeneration of glass nanofluidic chips through a multiple-step sequential thermochemical decomposition process at high temperatures. AB - Due to the lack of regeneration methods, the reusability of nanofluidic chips is a significant technical challenge impeding the efficient and economic promotion of both fundamental research and practical applications on nanofluidics. Herein, a simple method for the total regeneration of glass nanofluidic chips was described. The method consists of sequential thermal treatment with six well designed steps, which correspond to four sequential thermal and thermochemical decomposition processes, namely, dehydration, high-temperature redox chemical reaction, high-temperature gasification, and cooling. The method enabled the total regeneration of typical 'dead' glass nanofluidic chips by eliminating physically clogged nanoparticles in the nanochannels, removing chemically reacted organic matter on the glass surface and regenerating permanent functional surfaces of dissimilar materials localized in the nanochannels. The method provides a technical solution to significantly improve the reusability of glass nanofluidic chips and will be useful for the promotion and acceleration of research and applications on nanofluidics. PMID- 26278887 TI - Magnesium-catalysed hydroboration of isonitriles. AB - A beta-diketiminato magnesium alkyl complex is shown to be an effective pre catalyst for the first reported catalytic hydroboration of organic isonitriles, RNC, with HBpin. The reaction proceeds under mild conditions when R = alkyl and provides access to the corresponding 1,2-diborylated amine products. PMID- 26278886 TI - Chemotherapy in the oldest old: The feasibility of delivering cytotoxic therapy to patients 80 years old and older. AB - OBJECTIVES: Cancer is predominantly a disease of the elderly. While "older" patients are frequently considered for chemotherapy, little data exist in the population 80 years and older (80+). We investigated outcomes of patients 80+ who received chemotherapy at our institution. MATERIALS AND METHODS: A retrospective chart review of patients 80+ initiating chemotherapy for malignant solid tumors from 2005 to 2010 was performed. Baseline demographics, cancer type and chemotherapy data were collected. Primary outcome was the rate of discontinuation due to toxicity. Secondary outcomes included the rate of dose reduction/omission/delay (ROD), hospitalization and blood transfusion. RESULTS: Chemotherapy was initiated in 318 patients. Baseline demographics included the following: median age 82 years (80-92 years), 56% male, 55% ECOG PS 0-1, 43% Charlson index score of 0-1; 38% were taking >= 6 prescription medications. Common malignancies were colorectal (32%), lung (20%), and breast (12%). Most patients (68%) had metastatic disease or received palliative intent therapy (71%). Treatment was first line in 89% of patients, and an up front dose reduction was ordered in 41%. Toxicity caused therapy discontinuation in 32% of cases, while 52% experienced dose ROD. Hospitalization occurred in 32%; 18% required blood transfusions. Baseline polypharmacy was associated with increased hospitalization risk (OR 2.28, 95% CI 1.34-3.88, p=0.002), but dose adjustments were not correlated with any outcome. CONCLUSION: In this study, we observed a high risk of hospitalization or treatment discontinuation due to toxicity, despite frequent dose modifications. As the cancer population ages, validated tools are needed to better select patients for therapy. PMID- 26278888 TI - Common genetic risk factors for coronary artery disease: new opportunities for prevention? AB - Atherosclerotic cardiovascular disease (CVD) is a leading cause of mortality and morbidity worldwide, with coronary artery disease (CAD) being the single leading cause of death. Better control of risk factors, enhanced diagnostic techniques and improved medical therapies have all substantially decreased the mortality of CAD in developed countries. However, CAD and other forms of atherosclerotic CVD are projected to remain the leading cause of death by 2030 and we face a number of challenges if the outcomes of CAD are to be further improved. The fact that a substantial fraction of high-risk subjects do not reach treatment goals for important risk factors is one of these challenges. At the same time, there is also a non-negotiable fraction of 'concealed' high-risk subjects who are not detected by current risk algorithms and diagnostic modalities. In recent years, we have started to rapidly increase our knowledge of the framework of common genetics underlying CAD and atherosclerotic CVD in the population. In conjunction with modern diagnostic and therapeutic options, this new genetic knowledge may provide a valuable tool for further improvements in prevention. This review summarizes the recent findings from the search for common genetic risk factors for CAD. Furthermore, the author discusses how such recent findings could potentially be used in a number of clinical applications within CAD prevention, including in clinical risk stratification, in prediction of drug treatment response and in the search for targets for novel preventive therapies. PMID- 26278889 TI - Serum REG3alpha and C-Reactive Protein Levels in Crohn's Disease Patients Undergoing Immunoablation and Autologous Hemopoetic Stem Cell Transplantation in the ASTIC Trial. AB - BACKGROUND: REG3alpha has been recently shown to be a highly accurate biomarker for graft-versus-host-disease (GvHD). Given the unmet need of such biomarkers in Crohn's disease (CD) and the similarities between CD and GvHD, we aimed at investigating the role of serum REG3alpha as a diagnostic and prognostic biomarker in CD patients undergoing autologous hemopoetic stem cell transplantation (HSCT) in the multicenter Autologous Stem Cell Transplantation International Crohn's Disease (ASTIC) trial and to compare it to C-reactive protein (CRP). METHODS: Stored serum samples from the ASTIC trial were analyzed using a commercially available human PAP1 ELISA-kit to measure REG3alpha levels. CRP was available from prior analysis in the ASTIC trial. These levels were correlated with clinical and endoscopic disease activity as well as overall clinical and endoscopic outcome 1 year after autologous HSCT. RESULTS: One hundred thirty two serum samples were available for analysis. The mean concentration of REG3alpha was 101.8 ng/ml (95% CI 22.6-258.3). No significant elevation of REG3alpha was found among patients with active disease compared to those in remission (106.3 vs. 91.4). Patients with moderate to severe endoscopic disease activity showed substantially, although not significantly elevated REG3alpha levels compared to those in remission (95.4 vs. 52.4, p = 0.052). Baseline serum REG3alpha levels of patients without clinical or endoscopic remission 1 year after HSCT were not elevated compared to those in remission (63.1 vs. 66.9, and 68.4 vs. 59.2, respectively). In contrast, CRP was significantly elevated in patients with active disease compared to patients in remission (14.1 vs. 6.0 mg/dl, p = 0.032). In addition, CRP was elevated, although not significantly, in patients with severe endoscopic disease compared to those in endoscopic remission (18.7 vs. 4.1, p = 0.062). Furthermore, baseline CRP was reduced in patients with clinical and endoscopic remission after HSCT compared to those without remission, although not significantly (8.8 vs. 21.4, n.s. and 8.1 vs. 12.4, n.s.). CONCLUSION: Given the divergent findings compared to GvHD, we conclude that serum REG3alpha is not an accurate diagnostic and predictive biomarker in CD patients undergoing HSCT. In contrast, CRP is a valuable biomarker in order to differentiate active disease from remission. However, CRP does not seem to be of prognostic value for HSCT outcome. PMID- 26278890 TI - Total Knee Arthroplasty Failure Induced by Metal Hypersensitivity. AB - BACKGROUND: Metal hypersensitivity is an uncommon complication after total knee arthroplasty (TKA) that can lead to significant functional impairment and aseptic prosthesis failure. CASE REPORT: We describe a 70-year-old patient who presented with persistent pain, swelling, and instability 2 years after a primary TKA. The patient had a history of metal hypersensitivity following bilateral metal-on metal total hip arthroplasty (THA) that was revised to ceramic-on-polyethylene implants. Knee radiographs showed severe osteolysis with implant loosening. Serum cobalt was elevated and serum chromium was significantly elevated, while joint aspiration and inflammatory marker levels ruled out a periprosthetic infection. Revision TKA was performed, with intraoperative tissue pathology and postoperative leukocyte transformation testing confirming metal hypersensitivity as the cause for aseptic implant failure. CONCLUSIONS: This case report demonstrates the clinical and laboratory signs that suggest metal hypersensitivity in total knee arthroplasty and the potential for joint function restoration with revision surgery. PMID- 26278891 TI - Effect of emptying the vasculature before performing regional limb perfusion with amikacin in horses. AB - REASONS FOR PERFORMING STUDY: Emptying the vasculature with an Esmarch bandage before i.v. regional anaesthesia is commonly performed in human patients to prevent leakage of the solution under the tourniquet but there is no evidence for its efficacy in horses for antimicrobial i.v. regional limb perfusion (IV-RLP). OBJECTIVES: To determine the effect on synovial fluid concentration of amikacin of emptying the vasculature before performing IV-RLP. STUDY DESIGN: Crossover experiment. METHODS: Eight clinically healthy horses underwent 2 IV-RLP with amikacin in a randomised, crossover design. Horses received an IV-RLP with amikacin with or without exsanguination before applying a pneumatic tourniquet at the level of the forearm. Blood was collected from the jugular vein (before tourniquet removal) and synovial fluid from the radiocarpal and metacarpophalangeal joints (5 min after tourniquet removal and at 24 h) for amikacin determination. The procedure was video recorded to assess horse movement. RESULTS: There was no difference in amikacin concentrations in the plasma or synovial fluid from the radiocarpal joint between groups. There was a higher concentration of amikacin in the synovial fluid from the metacarpophalangeal joint immediately after tourniquet removal in the group with exsanguination of the limb prior to IV-RLP (mean +/- s.d.: no exsanguination 49.7 +/- 53.7 MUg/ml, exsanguination 257.4 +/- 149.7 MUg/ml, P = 0.04). Horse movement did not differ significantly between groups. CONCLUSIONS: Emptying the vasculature with an Esmarch bandage before IV-RLP can improve amikacin concentrations in the metacarpophalangeal joint of horses with no effect on the levels of amikacin in the radiocarpal joint. PMID- 26278893 TI - Is dasatinib-related pulmonary hypertension a clinical concern? PMID- 26278892 TI - The Cremeomycin Biosynthetic Gene Cluster Encodes a Pathway for Diazo Formation. AB - Diazo groups are found in a range of natural products that possess potent biological activities. Despite longstanding interest in these metabolites, diazo group biosynthesis is not well understood, in part because of difficulties in identifying specific genes linked to diazo formation. Here we describe the discovery of the gene cluster that produces the o-diazoquinone natural product cremeomycin and its heterologous expression in Streptomyces lividans. We used stable isotope feeding experiments and in vitro characterization of biosynthetic enzymes to decipher the order of events in this pathway and establish that diazo construction involves late-stage N-N bond formation. This work represents the first successful production of a diazo-containing metabolite in a heterologous host, experimentally linking a set of genes with diazo formation. PMID- 26278894 TI - Acute Silent Brain Infarction in Monocular Visual Loss of Ischemic Origin. AB - BACKGROUND AND PURPOSE: Non-arteritic branch/central retinal artery occlusions (BRAO/CRAO) and amaurosis fugax (AF) are predominantly caused by embolism. Additionally, transported embolic material could cause ischemic stroke. The aim of the study was to investigate the prevalence, pattern and underlying cause of concurrent acute brain infarctions in unselected patients with RAO and AF. METHODS: A total of 213 consecutive patients with BRAO (20.7%), CRAO (47.4%), or AF (31.9%) were retrospectively studied from 2008 to 2013. Magnetic resonance imaging (MRI) was used to detect acute brain infarctions and a cardiovascular workup was performed to detect underlying etiologies according to the Trial of Org 10172 in Acute Stroke Management (TOAST). RESULTS: MRI was obtained after 23.78 (+/-32.26) hours from the time of symptom onset. Acute brain infarctions were detected in 49 patients (23%); 44 of them (89.8%) did not experience any additional neurological symptoms. Older age (p < 0.001/p < 0.001), hypertension (p = 0.01/p = 0.03), atrial fibrillation (p = 0.006/p = 0.03) and type of RAO (p = 0.02/p = 0.016) were associated with total/silent stroke, respectively. In multivariate analysis, only age and type of occlusion remained positive predictors for silent stroke. Etiology of BRAO/CRAO and AF remained undetermined in 124 patients (58.2%). This rate was lower in patients with acute stroke (40.8 vs. 63.4%). CONCLUSIONS: Silent brain infarction is a frequent finding in unselected patients with BRAO/CRAO and AF. Etiology remains undetermined in approximately every second case. Because silent brain infarctions bear a high risk of future stroke, patients with BRAO/CRAO and AF should undergo prompt neuroimaging and cardiovascular checkup, preferably on a stroke unit. PMID- 26278895 TI - Assessment of 25-Hydroxyvitamin D Levels in Patients with Resistant Hypertension. AB - OBJECTIVE: To investigate the possible correlation between serum 25 hydroxyvitamin D levels and resistant hypertension (RH). SUBJECTS AND METHODS: Patients who had undergone ambulatory blood pressure measurements (ABPM) during outpatient controls were enrolled. Fifty subjects with RH, 50 with controlled hypertension (CHT) and 50 normotensive subjects (NT) were included in the study. RH was defined as 'suboptimal blood pressure control despite using 3 antihypertensive agents including a diuretic or need for 4 or more drugs to control blood pressure'. The 25-hydroxyvitamin D and parathormone levels were compared between the groups. Pearson's correlation coefficient test was applied to assess the correlation between 25-hydroxyvitamin D levels and office blood pressure (BP) and ABPM. Logistic regression analysis was used to determine the independent correlates of RH. RESULTS: The 25-hydroxyvitamin D level was significantly lower in the RH group (17.02 +/- 5.4 ng/ml) compared to the CHT (24.9 +/- 4.8 ng/ml) and NT groups (28.0 +/- 5.7 ng/ml, p < 0.001). In univariate correlation analysis, 25-hydroxyvitamin D levels had a significant negative correlation with office systolic BP (r = -0.329, p < 0.001), office diastolic BP (r = -0.395, p < 0.001), systolic ambulatory BP (r = -0.844, p = 0.004), and diastolic ambulatory BP (r = -0.567, p = 0.005). ROC analysis revealed that 25 hydroxyvitamin D levels <21.50 ng/ml predicted the presence of RH with a sensitivity of 78% and a specificity of 79% (AUC = 0.89, 95% CI 0.83-0.94). In the multivariate logistic regression analysis, 25-hydroxyvitamin D level was independently correlated with the presence of RH (beta 0.660, 95% CI 0.572-0.760, p < 0.001). CONCLUSION: There was an independent correlation between lower 25 hydroxyvitamin D levels and presence of RH. PMID- 26278896 TI - Quality of the Solimoes River water for domestic use by the riverine community situated in Manacapuru-Amazonas-Brazil. AB - The Amazon has the largest watershed in the world, with abundant fresh water reserves. Such abundance contrasts with the quality of the water consumed in the riverine communities. This work highlights the importance of assessing the quality of water of the Solimoes River in the stretch situated opposite the Community Nossa Senhora das Gracas-Costa do Pesqueiro, in front of the town of Manacapuru-Amazonas-Brazil. The research aimed to evaluate environmental indicators for the quality of the river water as well as in households in this community, according to the regional seasonality. The monitored parameters such as conductivity, dissolved oxygen, turbidity, color, pH, nitrate, nitrite, and sulfate were compared with the water quality standards in force in Brazil. Values well above the maximum level allowed (MLA) for color and turbidity parameters were found in some households, indicating that the water collected from the river is not getting appropriate treatment. The analysis of the correlation matrix of the parameters in the flood period of the river evidenced high correlation among dissolved oxygen (D.O), NO3 (-), Cl(-), SO4 (2-), and color. In this study, by principal component analysis (PCA), it was observed that the characteristics of the water, obtained from the river to be consumed in the households, in the flood period showed similarities with the river water samples, indicating absence of efficient treatment for human consumption. PMID- 26278897 TI - Abiotic reductive dechlorination of cis-DCE by ferrous monosulfide mackinawite. AB - Cis-1,2,-dichloroethylene (cis-DCE) is a toxic, persistent contaminant occurring mainly as a daughter product of incomplete degradation of perchloroethylene (PCE) and trichloroethylene (TCE). This paper reports on abiotic reductive dechlorination of cis-DCE by mackinawite (FeS1-x), a ferrous monosulfide, under variable geochemical conditions. To assess in situ abiotic cis-DCE dechlorination by mackinawite in the field, mackinawite suspensions prepared in a field groundwater sample collected from a cis-DCE contaminated field site were used for dechlorination experiments. The effects of geochemical variables on the dechlorination rates were monitored. A set of dechlorination experiments were also carried out in the presence of aquifer sediment from the site over a range of pH conditions to better simulate the actual field situations. The results showed that the suspensions of freshly prepared mackinawite reductively transformed cis-DCE to acetylene, whereas the conventionally prepared powder form of mackinawite had practically no reactivity with cis-DCE under the same experimental conditions. Significant cis-DCE degradation by mackinawite has not been reported prior to this study, although mackinawite has been shown to reductively transform PCE and TCE. This study suggests feasibility of using mackinawite for in situ remediation of cis-DCE-contaminated sites with high S levels such as estuaries under naturally achieved or stimulated sulfate-reducing conditions. PMID- 26278898 TI - Diazotrophic bacterial community variability in a subtropical deep reservoir is correlated with seasonal changes in nitrogen. AB - Nitrogen-fixing microorganisms (diazotrophs) play important roles in aquatic biogeochemistry and ecosystem functioning. However, little is known about the spatiotemporal variation of diazotrophic microbial communities in deep subtropical reservoirs. In this study, denaturing gradient gel electrophoresis (DGGE), clone libraries, quantitative PCR, and quantitative reverse transcription (RT)-PCR were used together to examine the vertical and seasonal patterns of diazotrophic microbial communities based on nitrogenase (nifH) gene sequences in the Dongzhen Reservoir, China, across time (every 3 months for 1 year) and space (five different water depths). In general, the numbers of DGGE bands increased with water depth during the stratification seasons (spring, summer, and autumn), with the clone-library-based operational taxonomic unit (OTU) number and nifH gene diversity being highest in autumn (6 OTUs at depth 0 m; 15 OTUs at 33 m) and winter (12 OTUs at 0 m, 13 OTUs at 33 m) but decreasing drastically in spring (2 OTUs at 0 m, 3 OTUs at 33 m) and summer (3 OTUs at 0 m, 2 OTUs at 33 m). The nifH gene abundance was lowest in the water mixing season (winter average, 5.17 * 10(7) copies/L) but increased in the three other seasons (9.03 * 10(9) copies/L). Cyanobacteria (dominated by filamentous thermophilic cyanobacteria and Cylindrospermopsis raciborskii) were the most dominant diazotrophic group at all depths and seasons, while both alphaproteobacteria and gammaproteobacteria were co-dominant in the bottom waters in autumn and winter. The distinct seasonal and spatial patterns in diazotrophic communities were significantly related to total nitrogen (TN) and ammonium nitrogen (NH4-N) in the reservoir (P < 0.01). Further, TN showed a significant positive correlation with nifH RNA copy number (P < 0.05) and DGGE band number (P < 0.01), whereas the NH4-N was negatively correlated with nifH DNA copy number (P < 0.01) and positively with both RNA/DNA ratio (P < 0.01) and DGGE band number (P < 0.01). Our data indicated that water stratification, mixing, and nitrogen might drive the diazotrophic community structure and activity in complex ways, thereby influencing the aquatic nitrogen cycle. Therefore, adaptive reservoir management strategies should carefully consider the effects of water stratification for protecting drinking water quality and for controlling the potential for diazotrophic cyanobacteria blooms. PMID- 26278899 TI - Effect of pectin on adsorption of Cu(II) by two variable-charge soils from southern China. AB - The influence of pectin on Cu(II) adsorption by two variable-charge soils (an Oxisol and an Ultisol) was investigated. Pectin increased the adsorption, and the extent of adsorption increased linearly with the dose of pectin, being greater in the Oxisol than that in the Ultisol because the adsorption of pectin by the Oxisol was greater. Both Langmuir and Freundlich equations fitted the adsorption isotherms of Cu(II) for both soils well. The fitting parameters of both equations indicated that pectin increased not only the adsorption capacity of the soils for Cu(II) but also the adsorption strength of Cu(II). The effect of pectin decreased with rising pH in the pH range 3.5-6.0, although the extent of electrostatic adsorption of Cu(II) by both soils was markedly greater over the pH range. Fourier-transformed infrared spectroscopy analysis and zeta potential measurement of soil colloids indicated that adsorption of pectin by the soils made the negative charge on both soils more negative, which was responsible for the increase in the electrostatic adsorption of Cu(II) induced by the addition of pectin. In conclusion, pectin-enhanced adsorption of Cu(II) especially at low pH would be beneficial to the soils as it would decrease the activity and mobility of Cu(II) in acidic variable-charge soils. PMID- 26278900 TI - Effects of imidacloprid on soil microbial communities in different saline soils. AB - The effects of imidacloprid in the soil environment are a worldwide concern. However, the impact of imidacloprid on soil microorganisms under salt stress is almost unknown. Therefore, an indoor incubation test was performed, and the denaturing gradient gel electrophoresis (DGGE) approach was used to determine the response of different saline soil bacterial and fungal community structures to the presence of imidacloprid (0.4, 2, 10 mg kg(-1)). The results showed that the soil bacterial diversity slightly declined with increasing imidacloprid concentration in soils with low salinity. In moderately saline soils, a new band in the DGGE profile suggested that imidacloprid could improve the soil bacterial diversity to some degree. An analysis of variance indicated that the measured soil bacterial diversity parameters were significantly affected by dose and incubation time. Compared with the control, the soil fungal community structure showed no obvious changes in low and moderately saline soils treated with imidacloprid. The results of these observations provide a basic understanding of the potential ecological effects of imidacloprid on different microorganisms in saline soils. PMID- 26278901 TI - Co-occurrence of arsenic and fluoride in the groundwater of Punjab, Pakistan: source discrimination and health risk assessment. AB - The present study discusses elevated groundwater arsenic (As) and fluoride (F(-)) concentrations in Mailsi, Punjab, Pakistan, and links these elevated concentrations to health risks for the local residents. The results indicate that groundwater samples of two areas of Mailsi, Punjab were severely contaminated with As (5.9-507 ppb) and F(-) (5.5-29.6 ppm), as these values exceeded the permissible limits of World Health Organization (10 ppb for As and 1.5 ppm for F( )). The groundwater samples were categorized by redox state. The major process controlling the As levels in groundwater was the adsorption of As onto PO4 (3-) at high pH. High alkalinity and low Ca(2+) and Mg(2+) concentrations promoted the higher F(-) and As concentrations in the groundwater. A positive correlation was observed between F(-) and As concentrations (r = 0.37; n = 52) and other major ions found in the groundwater of the studied area. The mineral saturation indices calculated by PHREEQC 2.1 suggested that a majority of samples were oversaturated with calcite and fluorite, leading to the dissolution of fluoride minerals at alkaline pH. Local inhabitants exhibited arsenicosis and fluorosis after exposure to environmental concentration doses of As and F(-). Estimated daily intake (EDI) and target hazard quotient (THQ) highlighted the risk factors borne by local residents. Multivariate statistical analysis further revealed that both geologic origins and anthropogenic activities contributed to As and F(-) contamination in the groundwater. We propose that pollutants originate, in part, from coal combusted at brick factories, and agricultural activities. Once generated, these pollutants were mobilized by the alkaline nature of the groundwater. PMID- 26278902 TI - Fine and ultrafine particles in small cities. A case study in the south of Europe. AB - Ultrafine particles, PM2.5 and PM10 mass concentration, NO(x), Ozone, SO2, back trajectories of air masses and meteorological parameters were studied in a small city over the period February, 2013 to June, 2014. The profiles of PM2.5 and PM10 particles are provided, showing averaged values of 16.6 and 21.6 MUg m(-3), respectively. The average number concentration of particles in the range of diameters 5.6-560 nm was 1.2 * 10(4)#/ cm(3) with contributions of 42, 51 and 7% from the nucleation, Aitken, and accumulation modes, respectively. The average number concentration of ultrafine particles was 1.1 * 10(4)#/ cm(3). The results obtained are evidence for some differences in the pollution of ambient air by particles in the studied town in comparison to bigger cities. Nucleation events due to emissions from the city were not observed, and traffic emissions amount to a small contribution to PM2.5 and PM10 particles which are mainly due to crustal origin from the arid surroundings and long-range transport from the Sahara Desert. PMID- 26278903 TI - Polybrominated diphenyl ethers in air and fallouts from an e-waste polluted region in southeast China: insight into levels, compositional profiles, and seasonal variation. AB - Air and fallout samples were collected seasonally in an e-waste polluted region in southeast of China in 2013-2014. The annual polybrominated diphenyl ethers (PBDEs) concentrations in air and fallout samples were 200 +/- 162 pg m(-3) and 320 +/- 255 ng g(-1), respectively. The deposition flux calculated from the fallout concentration was 110 +/- 77.3 ng m(-2) day(-1). The PBDE levels and deposition fluxes of the samples deployed within the e-waste central area were three to four times higher than those in the surrounding area. The congener profiles in the air samples could be commonly found in commercial penta-BDE mixtures. BDE209 was the most dominant congener in fallout samples. Debromination processes were confirmed to occur both in the air and fallouts due to the minor amounts or inexistence of some congeners in technical PBDE products. The highest gaseous PBDE concentration was found during the summer while lowest during the autumn. PBDE concentration in fallouts turned up higher in the cold months while lower in the warm months. The similarity of deposition fluxes at sites in the e waste central area indicated a steady PBDE emission source, whereas the significant relationship between deposition fluxes and particle weights at sites in the e-waste surrounding area suggested the scavenging of PBDEs in this area was largely associated with particles. PMID- 26278904 TI - Hydrolysis mechanism of methyl parathion evidenced by Q-Exactive mass spectrometry. AB - Organophosphorus pesticides (OPPs), a kind of widely used pesticides, are currently attracting great attention due to their adverse effects on human central nervous systems, particularly in children. Although the hydrolysis behavior of OPPs has been studied well, its hydrolysis mechanism remained controversial, especially at various pH conditions, partly due to their relatively complex structures and abundant moieties that were prone to be attacked by nucleophiles. The Q-Exactive mass spectrometer, part of those hybrid high-resolution mass spectrometers (HRMS), was used to determine hydrolysis products of methyl parathion (MP), a kind of OPPs in situ buffer aqueous solution with pH ranging from 1 to 13 in this study. Most of the complex hydrolysis products of MP were identified due to the high sensitivity and accuracy of HRMS. The results demonstrated that the hydrolysis rate and pathway of MP were strong pH dependent. With the increase of pH, the hydrolysis rate of MP increased, and two different reaction mechanisms were identified: SN (2)@P pathway dominated the hydrolysis process at high pH (e.g., pH >= 11) while SN (2)@C was the main behavior at low pH (e.g., pH <= 9). This study helps understand the hydrolysis mechanism of OPPs at various pH and extends the use of Q-Exactive mass spectrometry in identifying organic pollutants and their degradation products in environmental matrices. PMID- 26278905 TI - Comparison of oxytetracycline degradation behavior in pig manure with different antibiotic addition methods. AB - Using manure collected from swine fed with diet containing antibiotics and antibiotic-free swine manure spiked with antibiotics are the two common methods of studying the degradation behavior of veterinary antibiotic in manure in the environment. However, few studies had been conducted to co-compare these two different antibiotic addition methods. This study used oxytetracycline (OTC) as a model antibiotic to study antibiotic degradation behavior in manure under the above two OTC addition methods. In addition, the role of microorganisms present in the manure on degradation behavior was also examined. The results showed that degradation half-life of OTC in manure from swine fed OTC (9.04 days) was significantly shorter than that of the manure directly treated with OTC (9.65 days). Concentration of 4-epi-OTC in manure from swine fed OTC peaked earlier than that in manure spiked with OTC, and the degradation rates of 4-epi-OTC and alpha-apo-OTC in the manure from swine fed OTC were faster, but the peak concentrations were lower, than those in manure spiked with OTC. Bacterial diversity and relative abundance of Bacillus cereus data demonstrated that sterilization of the manure before experiment significantly decreased OTC degradation rate in both of the addition methods. Results of the present study demonstrated that the presence of the metabolites (especially 4-epi-OTC) and microorganisms had significant influence on OTC degradation. PMID- 26278906 TI - The occurrence of UV filters in natural and drinking water in Sao Paulo State (Brazil). AB - Ultraviolet (UV) filters are widely used in the formulation of personal care products (PCPs) to prevent damage to the skin, lips, and hair caused by excessive UV radiation. Therefore, large amounts of these substances are released daily into the aquatic environment through either recreational activities or the release of domestic sewage. The concern regarding the presence of such substances in the environment and the exposure of aquatic organisms is based on their potential for bioaccumulation and their potential as endocrine disruptors. Although there are several reports regarding the occurrence and fate of UV filters in the aquatic environment, these compounds are still overlooked in tropical areas. In this study, we investigated the occurrence of the organic UV filters benzophenone-3 (BP-3), ethylhexyl salicylate (ES), ethylhexyl methoxycinnamate (EHMC), and octocrylene (OC) in six water treatment plants in various cities in Southeast Brazil over a period of 6 months to 1 year. All of the UV filters studied were detected at some time during the sampling period; however, only EHMC and BP-3 were found in quantifiable concentrations, ranging from 55 to 101 and 18 to 115 ng L(-1), respectively. Seasonal variation of BP-3 was most clearly noticed in the water treatment plant in Araraquara, Sao Paulo, where sampling was performed for 12 months. BP-3 was not quantifiable in winter but was quantifiable in summer. The levels of BP-3 were in the same range in raw, treated and chlorinated water, indicating that the compound was not removed by the water treatment process. PMID- 26278907 TI - Is gene transcription in mussel gills altered after exposure to Ag nanoparticles? AB - Nanotechnology is a rapid field of development with the enhancement of the production of different types of nanoparticles (NPs) applied in several industrial and commercial applications which increase the risk of their presence in the aquatic environment. Ag NPs have a wide application in everyday life products. However, there is concern about the exposure effects on aquatic organisms to these NPs. Therefore, this study aims to assess gene transcription alterations in mussels Mytilus galloprovincialis gills exposed for 2 weeks to Ag NPs (42 +/- 10 nm, 10 MUg.L(-1)). The genes were selected based on previous biomarkers and proteomic results and included superoxide dismutase (SOD), catalase (CAT), glutathione transferase (GST), caspase 3/7-1 (CAS), cathepsin L (CATH), heat-shock protein 70 (HSP 70), cytochrome P450 4YA (CYP 4YA), the elongation factor (EF1), actin and alpha- tubulin. No significant changes in gene transcription profiles were observed after exposure of M. galloprovincialis to Ag NPs for 15 days. The lack of significant gene transcription responses is in light with previous results obtained for mussels exposed to these NPs and may be related to the fact that enzyme kinetics and relative abundance of proteins (increase of antioxidant enzymes and metalllothioneins (MTs) with the time of exposure) do not always directly reflect their relative mRNA levels. Nevertheless, their overall expression maintenance may signify that, at end of the exposure period (15 days), the transcription of the respective genes is no longer required, pointing out to a possible adaptation effect to nanoparticles or due to the levels of Ag NPs accumulated in this tissue at this exposure time. This study highlights that gene transcription application and role as an additional and/or alternative end point approach is important to understand the mode of action of these emergent contaminants in aquatic organisms. However, in future studies, the time window needs to be adjusted, as genes are likely to respond earlier to the nanoparticle exposure. PMID- 26278909 TI - Overlap between autism spectrum disorder and bipolar affective disorder. AB - BACKGROUND: At present there is a substantial uncertainty regarding the extent and nature of autism spectrum disorder (ASD) and bipolar affective disorder (BPAD) co-occurrence due to disparate findings in previous studies. This paper aimed to find and review original studies on co-occurrence rates of ASD with BPAD, assess them, synthesize the findings in a systematic way, present an overview and make recommendations for future research. METHODS: Systematic literature searches were performed using several databases. Selected articles had to describe an original study that provided prevalence and/or incidence analysis on ASD co-occurring together with BPAD. RESULTS AND CONCLUSION: A significant minority of patients (7%) with ASD suffers from BPAD. An accurate detection of co occurring ASD and BPAD can lead to a more targeted treatment and improve the patients' functioning and quality of life. PMID- 26278908 TI - The endocrine-disrupting effect and other physiological responses of municipal effluent on the clam Ruditapes decussatus. AB - In order to document the potential endocrine disrupting and toxic effect of the municipal wastewater effluents discharged into the Sfax coastal area (South of Tunisia), specimens of clam R. decussatus were collected from a reference site and were in vivo exposed to treated sewage effluent for 30 days. To this end, estrogenic and androgenic activities were measured in the gills to assess potential accumulation and regulation of active compounds. After effluent exposure androgenic activity in organic extracts increased up to fivefold compared to controls and remained elevated, while estrogenic activity was not significantly affected by exposure. As a consequence, remarkable disruptions in the gametogenesis activity, glycogen content, and Vitellogenin-like protein levels in male clams were observed. A parallel analysis of heavy metals in clam tissues was determined. A significant uptake of Ni, Zn, and Pb in soft tissues of exposed clams was observed. The significant increase of malondialdehyde (MDA) concentrations as a function of exposure time implies that clams have been exposed to an oxidative stress probably due to the presence of high metal concentrations in sewage effluent. Correlation analysis has revealed a statistically significant and positive relationship between MDA levels and metal concentrations in clams' tissues. The acetylcholinesterase activity was not significantly affected by exposure. Altogether, these results showed that a short term exposure to a mixture of chemical compounds released by the Sfax wastewater treatment plant induce adverse physiological and reproductive effects in R. decussatus. Further studies are underway in order to evaluate its long-term impacts on aquatic wildlife in the gulf of Gabes area. PMID- 26278910 TI - Effects of grass forage species and long-term period of low quality forage diet feeding on growth performance, nutrient utilization and microbial nitrogen yield in growing wether lambs. AB - Six growing lambs were used to evaluate the feeding value of two forage-based diets in a long-term feeding period by measuring body weight (BW) gain, digestibility, nitrogen (N) retention and microbial N (MBN) yield. The animals were fed imported low-quality timothy hay (TH) with concentrate diet (THD) or imported low-quality Italian ryegrass straw (IR) with concentrate diet (IRD) for 9 months. The forages were offered at 2% BW, and concentrate was fed at 40% of forage intake. The BW gain averaged 82.6 and 66.2 g/day for THD and IRD, respectively, without showing significant difference. Average forage intake (% BW) was significantly greater for IR than for TH, although it was not affected by feeding periods. The digestibility did not differ between diets or periods. The numerically greater (P = 0.06) ratio of retained N to absorbed N for IRD than that for THD was prominent. Neither diet nor period had significant effect on MBN supply and efficiency of MBN synthesis. The results suggest that the IR-based diet can be also used for long-term periods of feeding to growing ruminant animals as a grass hay-based diet without any detrimental effects on nutrient utilization and growth performance. PMID- 26278911 TI - Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants (EpoRepair). AB - BACKGROUND: Preterm infants suffering from intraventricular hemorrhage (IVH) are at increased risk for neurodevelopmental impairment. Observational data suggest that recombinant human erythropoietin (rEPO) improves long-term cognitive outcome in infants with IVH. Recent studies revealed a beneficial effect of early high dose rEPO on white matter development in preterm infants determined by magnetic resonance imaging (MRI). OBJECTIVES: To summarize the current evidence and to delineate the study protocol of the EpoRepair trial (Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants). METHODS: The study involves a review of the literature and the design of a double-blind, placebo-controlled, multicenter trial of repetitive high-dose rEPO administration, enrolling 120 very preterm infants with moderate-to-severe IVH diagnosed by cranial ultrasound in the first days of life, qualitative and quantitative MRI at term-equivalent age and long-term neurodevelopmental follow-up until 5 years of age. RESULTS AND CONCLUSIONS: The hypothesis generated by observational data that rEPO may improve long-term cognitive outcomes of preterm infants suffering from IVH are to be confirmed or refuted by the randomized controlled trial, EpoRepair. PMID- 26278912 TI - Peri-operative anaphylaxis: beyond drugs and latex. PMID- 26278913 TI - Skin Cancer Prevention, Tanning and Vitamin D: A Content Analysis of Print Media in Germany and Switzerland. AB - BACKGROUND: Print media are a major source of health information. OBJECTIVES: To analyse press coverage related to skin cancer prevention. METHODS: We conducted a content analysis of print media articles pertaining to skin cancer prevention, solaria and vitamin D published in Germany and Switzerland over a 1-year period between 2012 and 2013. RESULTS: Overall, 2,103 articles were analysed. Applying sunscreen was by far the most common sun protection recommendation. A considerable number of articles on solaria and vitamin D advocated exposure to ultraviolet radiation to enhance physical appearance and vitamin D photosynthesis, often without mentioning any precaution measures. In total, 26.8% of the articles contained misleading or erroneous statements mostly related to sunscreen use and vitamin D issues. CONCLUSIONS: Print media can serve as powerful education tools to foster skin cancer prevention. However, misleading or erroneous reports may negatively impact sun-safe behaviour. PMID- 26278914 TI - Regulation of Proteasomal Degradation by Modulating Proteasomal Initiation Regions. AB - Methods for regulating the concentrations of specific cellular proteins are valuable tools for biomedical studies. Artificial regulation of protein degradation by the proteasome is receiving increasing attention. Efficient proteasomal protein degradation requires a degron with two components: a ubiquitin tag that is recognized by the proteasome and a disordered region at which the proteasome engages the substrate and initiates degradation. Here we show that degradation rates can be regulated by modulating the disordered initiation region by the binding of modifier molecules, in vitro and in vivo. These results suggest that artificial modulation of proteasome initiation is a versatile method for conditionally inhibiting the proteasomal degradation of specific proteins. PMID- 26278915 TI - Spectrum of mutations in Indian patients with fibrinogen disorders and its application in genetic diagnosis of the affected families. PMID- 26278916 TI - Leap of Faith: Does Serum Luteinizing Hormone Always Accurately Reflect Central Reproductive Neuroendocrine Activity? AB - The function of the central aspects of the hypothalamic-pituitary-gonadal axis has been assessed in a number of ways including direct measurements of the hypothalamic output and indirect measures using gonadotropin release from the pituitary as a bioassay for reproductive neuroendocrine activity. Here, methods for monitoring these various parameters are briefly reviewed and then examples presented of both concordance and discrepancy between central and peripheral measurements, with a focus on situations in which elevated gonadotropin-releasing hormone neurosecretion is not reflected accurately by pituitary luteinizing hormone release. Implications for the interpretation of gonadotropin data are discussed. PMID- 26278918 TI - Hierarchical likelihood inference on clustered competing risks data. AB - The frailty model, an extension of the proportional hazards model, is often used to model clustered survival data. However, some extension of the ordinary frailty model is required when there exist competing risks within a cluster. Under competing risks, the underlying processes affecting the events of interest and competing events could be different but correlated. In this paper, the hierarchical likelihood method is proposed to infer the cause-specific hazard frailty model for clustered competing risks data. The hierarchical likelihood incorporates fixed effects as well as random effects into an extended likelihood function, so that the method does not require intensive numerical methods to find the marginal distribution. Simulation studies are performed to assess the behavior of the estimators for the regression coefficients and the correlation structure among the bivariate frailty distribution for competing events. The proposed method is illustrated with a breast cancer dataset. PMID- 26278917 TI - The Inhibition of Oxidised Low-Density Lipoprotein-Induced Apoptosis of Macrophages by Recombinant Human Brain Natriuretic Peptide and the Underlying Mechanism. AB - OBJECTIVE: Macrophage apoptosis plays a key role in atherosclerotic plaque rupture. This study investigated the effects of recombinant human brain natriuretic peptide (BNP) on oxidised low-density lipoprotein (ox-LDL)-induced macrophage apoptosis and explored the underlying mechanism. METHODS: A model of ox-LDL-induced macrophage injury was established to evaluate the role of BNP. Flow cytometry was employed to detect apoptosis and changes in mitochondrial membrane potential (x0394;x03A8;m), and confocal microscopy was used to determine cellular reactive oxygen species (ROS) levels. Additionally, reverse transcription-polymerase chain reaction and colourimetry were used to detect the mRNA expression and activity, respectively, of superoxide dismutase (SOD) and malondialdehyde (MDA). RESULTS: Ox-LDL induced macrophage apoptosis in a concentration-dependent manner, and maximum apoptosis occurred at 100 MUg/ml ox LDL (45.62 +/- 2.76 vs. 6.84 +/- 1.94%; p < 0.05). Conversely, BNP suppressed macrophage apoptosis, with a maximal effect at 10-9 mol/l (18.56 +/- 1.79%; p < 0.05). Compared with the control group, intracellular ROS levels increased, x0394;x03A8;m decreased, SOD mRNA expression and activity decreased and MDA mRNA expression and content increased in the 100-MUg/ml ox-LDL group (527.30 +/- 36.20 vs. 100.00 +/- 0.00%, 3.01 +/- 0.52 vs. 9.67 +/- 0.51%, 0.53 +/- 0.18 vs. 1.00 +/ 0.00, 256.6 +/- 8.20 vs. 355.8 +/- 9.58 U/ml, 1.59 +/- 0.23 vs. 1.00 +/- 0.00 and 29.4 +/- 1.68 vs. 5.94 +/- 0.51 nmol/ml; p < 0.05); these effects were significantly counteracted by 10-9 mol/l BNP (237.30 +/- 30.62%, 6.55 +/- 1.57%, 0.90 +/- 0.07, 310.4 +/- 2.97 U/ml, 1.14 +/- 0.10, 20.54 +/- 1.55 nmol/ml; p < 0.05). CONCLUSION: BNP attenuates ox-LDL-induced macrophage apoptosis by suppressing oxidative stress and preventing x0394;x03A8;m loss. PMID- 26278919 TI - Continuous Positive Airway Pressure in Patients With Obstructive Sleep Apnea and Resistant Hypertension: A Meta-Analysis of Randomized Controlled Trials. AB - This study aimed to analyze the effect of continuous positive airway pressure (CPAP) on blood pressure (BP) in patients with obstructive sleep apnea (OSA) and resistant hypertension. Randomized controlled trials (RCTs) that evaluated the effect of CPAP on BP in patients with OSA and resistant hypertension, indexed in MEDLINE, Embase, and the Cochrane Library from inception until March 20, 2015, were included in the meta-analysis. A total of five RCTs were identified to meet the inclusion criteria. The pooled changes after CPAP treatment for 24-hour ambulatory systolic BP and diastolic BP (DBP) were -4.78 mm Hg (95% confidence interval [CI], -7.95 to -1.61) and -2.95 mm Hg (95% CI, -5.37 to -0.53) in favor of the CPAP group. CPAP was also associated with reduction in nocturnal DBP (mean difference, -1.53 mm Hg, 95% CI, -3.07 to 0). The results indicated a favorable reduction in BP with CPAP treatment in patients with OSA and resistant hypertension. PMID- 26278920 TI - Laser processing of polymer constructs from poly(3-hydroxybutyrate). AB - CO2 laser radiation was used to process poly(3-hydroxybutyrate) constructs - films and 3D pressed plates. Laser processing increased the biocompatibility of unperforated films treated with moderate uniform radiation, as estimated by the number and degree of adhesion of NIH 3T3 mouse fibroblast cells. The biocompatibility of perforated films modified in the pulsed mode did not change significantly. At the same time, pulsed laser processing of the 3D plates produced perforated scaffolds with improved mechanical properties and high biocompatibility with bone marrow-derived multipotent, mesenchymal stem cells, which show great promise for bone regeneration. PMID- 26278921 TI - Durable remission of folliculotropic mycosis fungoides achieved with a combined topical treatment with cytarabine and carmustine. AB - Folliculotropic mycosis fungoides (MF) is an uncommon subtype of MF which has a more aggressive natural history and is more resistant to treatment than other forms of MF. In this article, an innovative method of treatment is presented. We describe a successful use of topical cytarabine combined with topical carmustine in a patient with a folliculotropic MF. Based on our patient history we suggest this method as an effective therapy option for patients with folliculotropic MF unresponsive to other forms of treatment. PMID- 26278922 TI - Serum S100A12 and Progression of Coronary Artery Calcification Over 4 Years in Hemodialysis Patients. AB - BACKGROUND/AIM: Vascular calcification is common and contributes to increased cardiovascular mortality in hemodialysis (HD) patients. In this prospective study, we aimed to investigate the associations of serum S100A12 in the presence of severe coronary artery calcification (CAC) and the progression of CAC in HD patients. METHODS: Sixty maintenance HD patients and 30 controls were enrolled. Serum S100A12 levels were measured using ELISA. CAC scores (CACs) were measured twice at a 4-year interval using multislice spiral CT. The HD patients were classified as rapid progressors or slow progressors according to the change in the CACs across these 2 measurements (x0394;CACs). RESULTS: The incidences of rapid progression of CAC in patients with baseline CACs <=10, CACs >10 and CACs >400 were 12.5, 40.0 and 64.3%, respectively. Both baseline and 4-year serum S100A12 levels were significantly higher in the rapid progressors than in the slow progressors (medians of 45.6 vs. 30.2 ng/ml, p < 0.001 and 62.3 vs. 39.4 ng/ml, p = 0.002, respectively). The serum S100A12 levels were significantly correlated with baseline CACs (r = 0.466, p < 0.001), 4-year CACs (r = 0.440, p < 0.001) and x0394;CACs (r = 0.392, p < 0.001). Importantly, the x0394;CACs were significantly correlated with x0394;S100A12 levels (r = 0.396, p < 0.001). Logistic regression analysis revealed that the serum S100A12 level was as an independent determinant of the presence of severe CAC and that the increment in the serum S100A12 level was a factor that was significantly independently associated with the progression of CAC. CONCLUSIONS: Serum S100A12 levels were significantly associated with the presence of severe CAC, and the increment in serum S100A12 levels was an independent determinant of the progression of CAC. PMID- 26278923 TI - Recent Advancement in the Treatment of Cardiovascular Diseases: Conventional Therapy to Nanotechnology. AB - Cardiovascular disease (CVD), accounting around 30% of deaths worldwide, collectively comprised of disorders affecting the heart and blood vessels as well as their associated adverse conditions. Despite outstanding progress in the area of the treatments of CVDs, significant challenges remain in designing of efficient delivery systems for myocardial therapy. Moreover, current therapy for CVDs is limited due to various clinical complications such as systemic toxicity, stent thrombosis, etc. Molecular and nanotechnology approaches provide the tools to explore such frontiers of biomedical science at the cellular level and thus offer unique features for potential application in the field of cardiac therapy. In this review, recent advances in CVD related risk factors, chronic inflammation, and their therapeutic modalities such as stem cell therapy, gene delivery, tissue factor (TF) inhibitors, miRNAs, leukotriene modifiers, thrombolytic agents etc., in modern molecular aspects are discussed. Moreover, nanoparticle based drug delivery, nanocarriers as molecular imaging, and the various challenges of myocardial tissue engineering aspects have been summarized. All these aspects may provide additional therapeutic substitutes in clinical trials for the registration of new drugs. PMID- 26278924 TI - Behavioral evidence for an impairment of affective theory of mind capabilities in chronic depression. AB - BACKGROUND: The only treatment specifically developed for chronic depression, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP), is based amongst others on the hypothesis that chronically depressed patients (CD) show considerable deficits of affective theory of mind (ToM) capabilities. Data are scarce, however, and it remains unclear if ToM deficits are specific or if they arise from global cognitive deficits associated with depression. This study investigates the specific deficits of affective ToM abilities in CD. SAMPLING AND METHODS: ToM abilities were assessed in 26 medication-free CD and 26 matched healthy controls (HC) by means of a previously established false-belief ToM cartoon task. Since the task allowed an intern control for cognitive factors - operationalized in a visuospatial ToM task - it was possible to investigate specific affective ToM deficits. RESULTS: As hypothesized, the CD showed a significant specific slowdown of affective ToM compared to cognitive ToM (3rd person perspective) when compared to HC. Simultaneously, we observed a general deterioration of all ToM functions in CD. CONCLUSIONS: This study provides evidence that CD have a mentalization deficit, specifically for affective ToM functions. This deficit is combined with a general deterioration of ToM functions, most likely attributable to frequently described cognitive deficits in depression. PMID- 26278925 TI - Longitudinal dose and type of immunosuppression in a national cohort of Australian liver, heart, and lung transplant recipients, 1984-2006. AB - Unconfounded comparative data on the type and dose of immunosuppressive agents among solid organ transplant recipients are sparse, as are data on longitudinal immunosuppressive therapy since transplantation. We addressed this issue in a population-based cohort of Australian liver (n = 1895), heart (n = 1220), and lung (n = 1059) transplant recipients, 1984-2006. Data on immunosuppressive therapy were retrospectively collected at discharge, three months, and one, five, 10, and 15 yr after first transplant. We computed unadjusted and adjusted estimates for the association between the type and dose of immunosuppressive therapy and organ type. After adjustment for confounders, use of induction antibody and maintenance corticosteroids was more common in heart and lung compared to liver recipients (p < 0.001), and antibody therapy for rejection more common in liver recipients (p < 0.001). Liver recipients were more likely to receive calcineurin inhibitor monotherapy, with or without corticosteroids, compared to heart and lung recipients (p < 0.001). Liver recipients consistently received lower doses of azathioprine than heart and lung recipients (p < 0.001). These differences in immunosuppression may partly explain variations in immunosuppression-related morbidity by transplanted organ, for example, malignancy risk. Longitudinal changes in the type and the dose of immunosuppressive therapy over time since transplantation also demonstrate the need for time-dependent data in observational research. PMID- 26278927 TI - Anion-pi Interactions with Fluoroarenes. PMID- 26278926 TI - Rapid and efficient one-step generation of paired gRNA CRISPR-Cas9 libraries. AB - The CRISPR-Cas9 system is a powerful tool to edit eukaryotic genomes that has recently been adapted for functional screens. Several of its applications- including the disruption of genes using Cas9-nickase and the generation of large deletions--require co-expression of two distinct guide RNAs (gRNAs). However, the lack of experimental approaches to generate pools of paired gRNA vectors prevents these applications from being scalable. Here we report a simple, inexpensive, one step method that allows for the rapid and efficient cloning of gRNA pairs into expression vectors. We show that this method can be used to generate pooled libraries and is therefore suitable for in vivo and in vitro functional screens. PMID- 26278928 TI - The Therapeutic Alliance Predicts Outcomes of Cognitive Behavior Therapy but Not of Mindfulness-Based Cognitive Therapy for Depressive Symptoms. PMID- 26278929 TI - Multi-dimensional Reduction and Transfer Function Design using Parallel Coordinates. AB - Multi-dimensional transfer functions are widely used to provide appropriate data classification for direct volume rendering. Nevertheless, the design of a multi dimensional transfer function is a complicated task. In this paper, we propose to use parallel coordinates, a powerful tool to visualize high-dimensional geometry and analyze multivariate data, for multi-dimensional transfer function design. This approach has two major advantages: (1) Combining the information of spatial space (voxel position) and parameter space; (2) Selecting appropriate high dimensional parameters to obtain sophisticated data classification. Although parallel coordinates offers simple interface for the user to design the high dimensional transfer function, some extra work such as sorting the coordinates is inevitable. Therefore, we use a local linear embedding technique for dimension reduction to reduce the burdensome calculations in the high dimensional parameter space and to represent the transfer function concisely. With the aid of parallel coordinates, we propose some novel high-dimensional transfer function widgets for better visualization results. We demonstrate the capability of our parallel coordinates based transfer function (PCbTF) design method for direct volume rendering using CT and MRI datasets. PMID- 26278931 TI - Endocasts and brain evolution in Anthracotheriidae (Artiodactyla, Hippopotamoidea). AB - Anthracotheres are a fossil family of 'Suiformes' from the Old World, North and Central America. They are known from the middle Eocene to the late Pliocene, and are suggested to be the stem group of Hippopotamidae. Yet, their soft anatomy remains poorly known. In this study we describe the virtual endocast of the late Oligocene anthracothere Microbunodon minimum, reconstructed using microtomography, as well as the natural endocast of Merycopotamus medioximus from the late Miocene. These are the first anthracothere endocasts ever described. Particular attention is given to the relative proportions of the brain, the neocortex, the cerebellum and the olfactory bulbs. The 'backward shift' of the pituitary of M. minimum, and the possible presence of a K lobe in M. medioximus, is discussed. Previous statements that some endocranial characters were subject to convergence among mammals are also corroborated. PMID- 26278930 TI - The human brain and face: mechanisms of cranial, neurological and facial development revealed through malformations of holoprosencephaly, cyclopia and aberrations in chromosome 18. AB - The study of inborn genetic errors can lend insight into mechanisms of normal human development and congenital malformations. Here, we present the first detailed comparison of cranial and neuro pathology in two exceedingly rare human individuals with cyclopia and alobar holoprosencephaly (HPE) in the presence and absence of aberrant chromosome 18 (aCh18). The aCh18 fetus contained one normal Ch18 and one with a pseudo-isodicentric duplication of chromosome 18q and partial deletion of 18p from 18p11.31 where the HPE gene, TGIF, resides, to the p terminus. In addition to synophthalmia, the aCh18 cyclopic malformations included a failure of induction of most of the telencephalon - closely approximating anencephaly, unchecked development of brain stem structures, near absence of the sphenoid bone and a malformed neurocranium and viscerocranium that constitute the median face. Although there was complete erasure of the olfactory and superior nasal structures, rudiments of nasal structures derived from the maxillary bone were evident, but with absent pharyngeal structures. The second non-aCh18 cyclopic fetus was initially classified as a true Cyclops, as it appeared to have a proboscis and one median eye with a single iris, but further analysis revealed two eye globes as expected for synophthalmic cyclopia. Furthermore, the proboscis was associated with the medial ethmoid ridge, consistent with an incomplete induction of these nasal structures, even as the nasal septum and paranasal sinuses were apparently developed. An important conclusion of this study is that it is the brain that predicts the overall configuration of the face, due to its influence on the development of surrounding skeletal structures. The present data using a combination of macroscopic, computed tomography (CT) and magnetic resonance imaging (MRI) techniques provide an unparalleled analysis on the extent of the effects of median defects, and insight into normal development and patterning of the brain, face and their skeletal support. PMID- 26278932 TI - Musculoskeletal anatomy and feeding performance of pre-feeding engyodontic larvae of the European eel (Anguilla anguilla). AB - Being part of the elopomorph group of fishes, Anguillidae species show a leptocephalus larval stage. However, due to largely unknown spawning locations and habitats of their earliest life stages, as well as their transparency, these Anguilla larvae are rarely encountered in nature. Therefore, information regarding the early life history of these larvae, including their exogenous feeding strategy and feeding performance, is rather scarce. To better understand the structural basis and functional performance of larval feeding in captivity, the functional morphology of the cranial musculoskeletal system in pre- and first feeding engyodontic leptocephali of the European eel (Anguilla anguilla) was studied. A 3D reconstruction of the feeding apparatus (head of the leptocephali < 1 mm) was used to visualize and describe the musculoskeletal changes throughout these stages. To analyze the ontogenetic changes in the functionality of the feeding apparatus towards the active feeding phase, 3D data of joints, levers and muscles derived from the reconstructions were used to estimate bite and joint reaction forces (JRFs). Observing a maximum estimated bite force of about 65 MUN (and corresponding JRFs of 260 MUN), it can be hypothesized that leptocephalus larvae are functionally constrained to feed only on soft food particles. Additionally, potential prey items are size delimited, based on the theoretically estimated average gape of these larvae of about 100 MUm. This hypothesis appears to be in line with recent observations of a diet consisting of small and/or gelatinous prey items (Hydrozoa, Thaliacea, Ctenophora, Polycystenia) found in the guts of euryodontic leptocephalus larvae. PMID- 26278934 TI - Theoretical Prediction of Carrier Mobility in Few-Layer BC2N. AB - An ideal semiconducting material should simultaneously hold a considerable direct band gap and a high carrier mobility. A 2D planar compound consisting of zigzag chains of C-C and B-N atoms, denoted as BC2N, would be a good candidate. It has a direct band gap of 2 eV, which can be further tuned by changing the layer number. At the same time, our first-principles calculations show that few-layer BC2N possesses a high carrier mobility. The carrier mobility of around one million sqaure centimeters per volt-second is obtained at its three-layer. As our study demonstrated, few-layer BC2N has potential applications in nanoelectronics and optoelectronics. PMID- 26278935 TI - [Not Available]. PMID- 26278936 TI - Formation of Helices in Graphene Nanoribbons under Torsion. AB - We use objective boundary conditions and self-consistent charge density functional-based tight-binding to simulate at the atomistic scale the formation of helices in narrow graphene nanoribbons with armchair edges terminated with fluorine and hydrogen. We interpret the microscopic data using an inextensible, unshearable elastic rod model, which considers both bending and torsional strains. When fitted to the atomistic data, the simple rod model uses closed-form solutions for a cubic equation to predict the strain energy and morphology at a given twist angle and the crossover point between pure torsion and a helix. Our modeling and simulation bring key insights into the origin of the helical graphene morphologies stored inside of carbon nanotubes. They can be useful for designing chiral nanoribbons with tailored properties. PMID- 26278933 TI - Time course and side-by-side analysis of mesodermal, pre-myogenic, myogenic and differentiated cell markers in the chicken model for skeletal muscle formation. AB - The chicken is a well-established model for amniote (including human) skeletal muscle formation because the developmental anatomy of chicken skeletal muscle matches that of mammals. The accessibility of the chicken in the egg as well as the sequencing of its genome and novel molecular techniques have raised the profile of this model. Over the years, a number of regulatory and marker genes have been identified that are suited to monitor the progress of skeletal myogenesis both in wildtype and in experimental embryos. However, in the various studies, differing markers at different stages of development have been used. Moreover, contradictory results on the hierarchy of regulatory factors are now emerging, and clearly, factors need to be able to cooperate. Thus, a reference paper describing in detail and side-by-side the time course of marker gene expression during avian myogenesis is needed. We comparatively analysed onset and expression patterns of the key markers for the chicken immature paraxial mesoderm, for muscle-competent cells, for cells committed to myogenesis and for cells entering terminal differentiation. We performed this analysis from stages when the first paraxial mesoderm is being laid down to the stage when mesoderm formation comes to a conclusion. Our data show that, although the sequence of marker gene expression is the same at the various stages of development, the timing of the expression onset is quite different. Moreover, marker gene expression in myogenic cells being deployed from the dorsomedial and ventrolateral lips of the dermomyotome is different from those being deployed from the rostrocaudal lips, suggesting different molecular programs. Furthermore, expression of Myosin Heavy Chain genes is overlapping but different along the length of a myotube. Finally, Mef2c is the most likely partner of Mrf proteins, and, in contrast to the mouse and more alike frog and zebrafish fish, chicken Mrf4 is co-expressed with MyoG as cells enter terminal differentiation. PMID- 26278937 TI - Controlling the Catalytic Efficiency on the Surface of Hollow Gold Nanoparticles by Introducing an Inner Thin Layer of Platinum or Palladium. AB - The efficiency of heterogeneous catalysis of electron-transfer reactions on the surface of gold nanoshells was changed by adding an inner platinum or palladium nanoshell in the double-shell nanocatalysts. The reduction of 4-nitrothiophenol (4NTP) by borohydride was studied as a model reaction. To confirm the heterogeneous catalytic mechanism, the nanocatalysts were assembled into a monolayer on the surface of a quartz substrate using the Langmuir-Blodgett technique, and the 4NTP was allowed to bind to the surface of gold through a strong thiol bond. The stages of the reduction reaction of 4NTP on the surface of gold were successfully followed by time-resolved surface-enhanced Raman spectroscopy. Palladium was found to increase the catalytic efficiency of the gold surface due to the presence of a new Fermi level of the palladium-gold alloy, while platinum decreased its catalytic efficiency due to the electron withdrawing effect of platinum atoms, which resulted from the difference in their electrochemical reduction potentials. PMID- 26278938 TI - Ionic Liquid Adsorption and Nanotribology at the Silica-Oil Interface: Hundred Fold Dilution in Oil Lubricates as Effectively as the Pure Ionic Liquid. AB - The remarkable physical properties of ionic liquids (ILs) make them potentially excellent lubricants. One of the challenges for using ILs as lubricants is their high cost. In this article, atomic force microscopy (AFM) nanotribology measurements reveal that a 1 mol % solution of IL dissolved in an oil lubricates the silica surface as effectively as the pure IL. The adsorption isotherm shows that the IL surface excess need only be approximately half of the saturation value to prevent surface contact and effectively lubricate the sliding surfaces. Using ILs in this way makes them viable for large-scale applications. PMID- 26278939 TI - Direct Observation of Gigahertz Coherent Guided Acoustic Phonons in Free-Standing Single Copper Nanowires. AB - We report on gigahertz acoustic phonon waveguiding in free-standing single copper nanowires studied by femtosecond transient reflectivity measurements. The results are discussed on the basis of the semianalytical resolution of the Pochhammer and Chree equation. The spreading of the generated Gaussian wave packet of two different modes is derived analytically and compared with the observed oscillations of the sample reflectivity. These experiments provide a unique way to independently obtain geometrical and material characterization. This direct observation of coherent guided acoustic phonons in a single nano-object is also the first step toward nanolateral size acoustic transducer and comprehensive studies of the thermal properties of nanowires. PMID- 26278940 TI - Magneto-Optical Properties of CuInS2 Nanocrystals. AB - We compare the absorption, photoluminescence, and magneto-optical properties of colloidal CuInS2 (CIS) nanocrystals with two closely related and well-understood binary analogs: Cu-doped ZnSe nanocrystals and CdSe nanocrystals. In contrast with conventional CdSe, both CIS and Cu-doped ZnSe nanocrystals exhibit a substantial energy separation between emission and absorption peaks (Stokes shift) and a marked asymmetry in the polarization-resolved low-temperature magneto-photoluminescence, both of which point to the role of localized dopant/defect states in the forbidden gap. Surprisingly, we find evidence in CIS nanocrystals of spin-exchange coupling between paramagnetic moments in the nanocrystal and the conduction/valence bands of the host lattice, a behavior also observed in Cu-doped ZnSe nanocrystals, where the copper atoms incorporate as paramagnetic Cu(2+) ions. PMID- 26278941 TI - Synergistic Effects of Alloying and Thiolate Modification in Furfural Hydrogenation over Cu-Based Catalysts. AB - Control of bimetallic surface composition and surface modification with self assembled monolayers (SAMs) represent two methods for modifying catalyst activity and selectivity. However, possible synergistic effects of employing these strategies in concert have not been previously explored. We investigated the effects of modifying Cu/Al2O3 catalysts by alloying with Ni and modifying with octadecanethiol (C18) SAMs, using furfural hydrogenation as a probe reaction. Incorporation of small amounts of Ni (Cu4Ni) improved catalytic activity while slightly reducing hydrogenation selectivity. Further incorporation of Ni resulted in high rates for decarbonylation and ring-opening. Modification of the Cu4Ni catalyst with C18-SAMs resulted in improvement in both the activity and hydrogenation selectivity. X-ray photoelectron spectroscopy experiments on bimetallic thin films and density functional theory calculations revealed that the C18-SAM kinetically stabilized Cu at the surface under hydrogenation conditions. These results indicate that thiolate monolayers can be used to control surface bimetallic composition to improve catalytic performance. PMID- 26278942 TI - On the Uniqueness of Ideality Factor and Voltage Exponent of Perovskite-Based Solar Cells. AB - Perovskite-based solar cells have attracted much recent research interest with efficiency approaching 20%. While various combinations of material parameters and processing conditions are attempted for improved performance, there is still a lack of understanding in terms of the basic device physics and functional parameters that control the efficiency. Here we show that perovskite-based solar cells have two universal features: an ideality factor close to two and a space charge-limited current regime. Through detailed numerical modeling, we identify the mechanisms that lead to these universal features. Our model predictions are supported by experimental results on solar cells fabricated at five different laboratories using different materials and processing conditions. Indeed, this work unravels the fundamental operation principle of perovskite-based solar cells, suggests ways to improve the eventual performance, and serves as a benchmark to which experimental results from various laboratories can be compared. PMID- 26278943 TI - Periodic MP2, RPA, and Boundary Condition Assessment of Hydrogen Ordering in Ice XV. AB - Ice XV is the hydrogen-ordered form of the ice VI phase whose structure was predicted to be Cc and ferroelectric using periodic DFT approaches. However, neutron diffraction and Raman spectroscopy data show the structure to have P1 symmetry and to be antiferroelectric. Recent work1 using fragment-based MP2 and CCSD(T) approaches predicts the experimental structure as the ground state. We have reconsidered this problem using fully periodic MP2 and RPA approaches and find that the ferroelectric Cc structure is the lowest energy configuration. However, ubiquitously employed tinfoil boundary conditions stabilize polar structures. We suggest that ferroelectric Cc crystals can grow within a paraelectric ice VI matrix but may become unstable once a fraction of the matrix has become hydrogen-ordered. The reduction in dielectric constant causes P1 and other structures with small polarization to become favored, providing a possible resolution between observation and theoretical predictions. PMID- 26278944 TI - Control of Carbon Nanotube Electronic Properties by Lithium Cation Intercalation. AB - We show that the electronic properties of single walled carbon nanotubes (SWCNTs) can be tuned continuously from semiconducting to metallic by varying the location of ions inside the tubes. Focusing on the Li(+) cation inside the (26,0) zigzag semiconducting and (15,15) armchair metallic SWCNTs, we found that the Li(+) SWCNT interaction is attractive. The interaction is stronger for the metallic SWCNT, indicating in particular that metallic tubes can enhance performance of lithium-ion batteries. The electronic properties of the metallic SWCNT are virtually independent of the presence of ions: Li(+) creates an energy level in the valence band slightly below the Fermi energy. On the contrary, the semiconducting SWCNT can be made metallic by placing ions close to the tube axis: Li(+) generates a new bottom of the conduction band. Letting the ions approach SWCNT walls recovers the semiconducting behavior. PMID- 26278945 TI - Recent Progress in the Functionalization Methods of Thiolate-Protected Gold Clusters. AB - Nanomaterials that exhibit both stability and functionality are currently considered to hold great promise as components of nanotechnology devices. Thiolate-protected gold clusters (Aun(SR)m) have long attracted attention as functional nanomaterials. Magic Aun(SR)m clusters are an especially stable group of thiolate-protected clusters that have particularly high potential as functional materials. Although numerous application experiments have been conducted for magic Aun(SR)m clusters, it is important that functionalization methods are also established to allow for effective utilization of these materials. The results of recent research on heteroatom doping and the use of other chalcogenide ligands strongly suggest that these strategies are promising as functionalization methods of magic Aun(SR)m clusters. In this Perspective, we focus on studies relating to three representative types of magic clusters Au25(SR)18, Au38(SR)24, and Au144(SR)60-and discuss the recent progress and future issues. PMID- 26278946 TI - Ion-Solvation-Induced Molecular Reorganization in Liquid Water Probed by Resonant Inelastic Soft X-ray Scattering. AB - The molecular structure of liquid water is susceptible to changes upon admixture of salts due to ionic solvation, which provides the basis of many chemical and biochemical processes. Here we demonstrate how the local electronic structure of aqueous potassium chloride (KCl) solutions can be studied by resonant inelastic soft X-ray scattering (RIXS) to monitor the effects of the ion solvation on the hydrogen-bond (HB) network of liquid water. Significant changes in the oxygen K edge emission spectra are observed with increasing KCl concentration. These changes can be attributed to modifications in the proton dynamics, caused by a specific coordination structure around the salt ions. Analysis of the spectator decay spectra reveals a spectral signature that could be characteristic of this structure. PMID- 26278947 TI - Unique Advantages of Exfoliated 2D Nanosheets for Tailoring the Functionalities of Nanocomposites. AB - Hybridization with exfoliated two-dimensional (2D) nanosheets provides a very effective and powerful way not only to control the physicochemical properties of hybridized species but also to explore nanocomposites with novel functionalities. Deliberate coupling between the hybridized species is critically important in maximizing the effect of hybridization on the physicochemical properties and functionality of hybridized components. The very small thickness and extremely large surface of exfoliated 2D nanosheets render these materials ideal candidates for achieving a strong coupling with diverse guest species. This Perspective focuses on the unique characteristics of exfoliated 2D nanosheets as building blocks for designing hybrid materials. Several intriguing examples of strong interaction between exfoliated 2D nanosheets and hybridized species are summarized with an emphasis on the effective control of electronic, optical, structural, and morphological characteristics. An outlook on the future research directions is provided along with new strategies to maximize the coupling in the 2D nanosheet-based hybrid materials. PMID- 26278949 TI - Emergence of New Materials for Light-Energy Conversion: Perovskites, Metal Clusters, and 2-D Hybrids. PMID- 26278948 TI - New Insights into the Electronic Transport of Reduced Graphene Oxide Using Scanning Electrochemical Microscopy. AB - The present work investigates the electronic conduction of reduced graphene oxide flakes and the coupling between flakes through a combined SECM (scanning electrochemical microscopy), AFM, and SEM analysis. Images of individual and interconnected flakes directly reveal the signature of the contact resistance between flakes in a noncontact and substrate-independent way. Quantitative evaluation of the parameters is achieved with the support of numerical simulations to interpret the experimental results. The interflakes contact resistance importantly impacts the transport of electrons, which can be anticipated as a key parameter in r-GO-based materials used in fuel cells, lithium batteries, supercapacitors, and organic electronic devices. PMID- 26278950 TI - Microalloying Boron Carbide with Silicon to Achieve Dramatically Improved Ductility. AB - Boron carbide (B4C) is a hard material whose value for extended engineering applications such as body armor; is limited by its brittleness under impact. To improve the ductility while retaining hardness, we used density functional theory to examine modifying B4C ductility through microalloying. We found that replacing the CBC chain in B4C with Si-Si, denoted as (B11Cp)-Si2, dramatically improves the ductility, allowing a continuous shear to a large strain of 0.802 (about twice of B4C failure strain) without brittle failure. Moreover, (B11C)-Si2 retains low density and high hardness. This ductility improvement arises because the Si-Si linkages enable the icosahedra accommodate additional shear by rotating instead of breaking bonds. PMID- 26278951 TI - Solution Chemistry Engineering toward High-Efficiency Perovskite Solar Cells. AB - Organic and inorganic hybrid perovskites (e.g., CH3NH3PbI3) have emerged as a revolutionary class of light-absorbing semiconductors that has demonstrated a rapid increase in efficiency within a few years of active research. Controlling perovskite morphology and composition has been found critical to developing high performance perovskite solar cells. The recent development of solution chemistry engineering has led to fabrication of greater than 15-17%-efficiency solar cells by multiple groups, with the highest certified 17.9% efficiency that has significantly surpassed the best-reported perovskite solar cell by vapor-phase growth. In this Perspective, we review recent progress on solution chemistry engineering processes and various control parameters that are critical to the success of solution growth of high-quality perovskite films. We discuss the importance of understanding the impact of solution-processing parameters and perovskite film architectures on the fundamental charge carrier dynamics in perovskite solar cells. The cost and stability issues of perovskite solar cells will also be discussed. PMID- 26278952 TI - Nonchaos-Mediated Mixed-Mode Oscillations in an Enzyme Reaction System. AB - We report numerical evidence of a new type of wide-ranging organization of mixed mode oscillations (MMOs) in a model of the peroxidase-oxidase reaction, in the control parameter plane defined by the supply of the reactant NADH and the pH of the medium. In classic MMOs, the intervals of distinct periodic oscillations are always separated from each other by windows of chaos. In contrast, in the new unfolding, such windows of chaos do not exist. Chaos-mediated and nonchaos mediated MMO phases are separated by a continuous transition boundary in the control parameter plane. In addition, for low pH values, we find an exceptionally wide and intricate mosaic of MMO phases that is described by a detailed phase diagram. PMID- 26278953 TI - Effect of Amine Surface Coverage on the Co-Adsorption of CO2 and Water: Spectral Deconvolution of Adsorbed Species. AB - Three primary amine materials functionalized onto mesoporous silica with low, medium, and high surface amine coverages are prepared and evaluated for binary CO2/H2O adsorption under dilute conditions. Enhancement of amine efficiency due to humid adsorption is most pronounced for low surface amine coverage materials. In situ FT-IR spectra of adsorbed CO2 on these materials suggest this enhancement may be associated with the formation of bicarbonate species during adsorption on materials with low surface amine coverage, though such species are not observed on high surface coverage materials. On the materials with the lowest amine loading, bicarbonate is observed on longer time scales of adsorption, but only after spectral contributions from rapidly forming alkylammonium carbamate species are removed. This is the first time that direct evidence for bicarbonate formation, which is known to occur in liquid aqueous amine solutions, has been presented for CO2 adsorption on solid amine adsorbents. PMID- 26278954 TI - Curvature and Lipid Packing Modulate the Elastic Properties of Lipid Assemblies: Comparing HII and Lamellar Phases. AB - Accumulating evidence indicates that membrane reshaping and fusion processes, as well as regulation of membrane protein function, depend on lipid composition. Although it is widely accepted that cell membranes are under considerable stress and frustration and can be locally highly curved, experimental approaches to determine the material properties of lipids usually rely on their study in a relaxed environment or in flat bilayers. Here, we propose a computational method to determine the elastic properties of lipid assemblies of arbitrarily shaped interfaces and apply it to lipidic mixtures in the inverted hexagonal and lamellar phases. We find that the bending rigidity critically depends on the geometry of the system and correlates with the changes in lipid chain order imposed by the specific environment. Our results are relevant for resolving local lipid properties of deformed, stressed, or frustrated membranes that notably emerge around integral membrane proteins or during different membrane remodeling processes. PMID- 26278955 TI - Enhanced Hole Extraction in Perovskite Solar Cells Through Carbon Nanotubes. AB - Here, we report the use of polymer-wrapped carbon nanotubes as a means to enhance charge extraction through undoped spiro-OMeTAD. With this approach a good solar cell performance is achieved without the implementation of conventional doping methods. We demonstrate that a stratified two-layer architecture of sequentially deposited layers of carbon nanotubes and spiro-OMeTAD, outperforms a conventional blend of the hole-conductor and the carbon nanotubes. We also provide insights into the mechanism of the rapid hole extraction observed in the two-layer approach. PMID- 26278956 TI - Relevance of the Channel Leading to Formaldehyde + Triplet Ethylidene in the O((3)P) + Propene Reaction under Combustion Conditions. AB - Comprehension of the detailed mechanism of O((3)P) + unsaturated hydrocarbon reactions is complicated by the existence of many possible channels and intersystem crossing (ISC) between triplet and singlet potential energy surfaces (PESs). We report synergic experimental/theoretical studies of the O((3)P) + propene reaction by combining crossed molecular beams experiments using mass spectrometric detection at 9.3 kcal/mol collision energy (Ec) with high-level ab initio electronic structure calculations of the triplet PES and RRKM/master equation computations of branching ratios (BRs) including ISC. At high Ec's and temperatures higher than 1000 K, main products are found to be formaldehyde (H2CO) and triplet ethylidene ((3)CH3CH) formed in a reaction channel that has never been identified or considered significant in previous kinetics studies at 300 K and that, as such, is not included in combustion kinetics models. Global and channel-specific rate constants were computed and are reported as a function of temperature and pressure. This study shows that BRs of multichannel reactions useful for combustion modeling cannot be extrapolated from room-temperature kinetics studies. PMID- 26278957 TI - Stress Test for Quantum Dynamics Approximations: Deep Tunneling in the Muonium Exchange Reaction D + HMu -> DMu + H. AB - Quantum effects play a crucial role in chemical reactions involving light atoms at low temperatures, especially when a light particle is exchanged between two heavier partners. Different theoretical methodologies have been developed in the last decades attempting to describe zero-point energy and tunneling effects without abandoning a classical or semiclassical framework. In this work, we have chosen the D + HMu -> DMu + H reaction as a stress test system for three well established methods: two representative versions of transition state theory (TST), canonical variational theory and semiclassical instanton, and ring polymer molecular dynamics (RPMD). These calculations will be compared with accurate quantum mechanical results. Despite its apparent simplicity, the exchange of the extremely light muonium atom (0.114 u) becomes a most challenging reaction for conventional methods. The main result of this work is that RPMD provides an overall better performance than TST-based methods for such a demanding reaction. RPMD might well turn out to be a useful tool beyond TST applicability. PMID- 26278958 TI - Positively Charged Phosphorus as a Hydrogen Bond Acceptor. AB - Phosphorus (P) is an element that is essential to the life of all organisms, and the atmospheric detection of phosphine suggests the existence of a volatile biogeochemical P cycle. Here, we investigate the ability of P to participate in the formation of OH...P hydrogen bonds. Three bimolecular alcohol trimethylphosphine complexes have been detected. Initially, the complexes were detected using matrix isolation spectroscopy, which favors complex formation. Subsequently, the fundamental OH-stretching vibration was observed in room temperature gas-phase spectra. On the basis of our measured OH-stretching frequency red shifts and quantum chemical calculations, we find that P is an acceptor atom similar in strength to O and S and that all three P, O, and S atoms are weaker acceptors than N. The quantum chemical calculations show that both H and P in the OH...P hydrogen bond have partial positive charges, as expected from their electronegativities. However, the electrostatic potentials show a negative potential area on the electron density surface around P that facilitates formation of hydrogen bonds. PMID- 26278959 TI - Duration of dual antiplatelet therapy after drug-eluting stent implantation: Meta analysis of large randomised controlled trials. AB - Patients receive dual antiplatelet therapy (DAPT) for 6-12 months after drug eluting stents (DES) implantation. The efficacy and safety of prolonged DAPT has been questioned. Therefore, we performed a meta-analysis on randomised trials comparing different DAPT durations. Literature was searched on trials comparing different DAPT durations. For inclusion, reports must report frequency of cardiovascular and bleeding events. Ten trials were included. Compared to 12 months, DAPT beyond 12 months was associated with fewer myocardial infarctions (OR 0.58 95%CI: 0.40-0.84) and stent thrombosis (OR 0.35 95%CI: 0.20-0.62), but more major bleeds (OR 1.60 95%CI: 1.22-2.11) and all-cause (OR 1.30 95%CI: 1.02 1.66) mortality. There was no significant alteration in risk of stroke (OR 0.93 95%CI: 0.66-1.31) or cardiac (OR 1.12 95%CI: 0.73-1.71) mortality. Compared to less than 12 months DAPT, 12 months DAPT did not reduce risk of myocardial infarction, stent thrombosis, strokes, cardiac or all-cause mortality, but increased the risk of major bleeds (OR 1.60 95%CI: 1.22-2.11). DAPT beyond 12 months reduce risk of myocardial infarction and stent thrombosis, but there is substantial increase in major bleeding risk and all-cause mortality which need to be addressed. DAPT beyond 12 months does not appear to alter the risk of stroke. PMID- 26278960 TI - Electrocardiogram before starting stimulant medications: to order or not? AB - D is an 8-year-old boy brought to his paediatrician for evaluation. His mother is concerned as his teacher has been frequently complaining that he is very restless and often disturbs the rest of the class by getting up on some pretext or the other. He is unable to concentrate on his work and gets distracted very easily. He makes many careless mistakes and can hardly finish his tasks on time. He is frequently reprimanded for talking during class. He often answers out of turn or before the question has been completed; however, so far, he has been managing to get passing grades. At home, he is constantly on the go while he is awake. If he is forced to sit, like at mealtimes, he fidgets a lot. He also needs to be constantly nagged to do everything, even his daily activities such as brushing his teeth, or he forgets to do them or leaves them incomplete. He takes ages to finish his food. It is a major job to get him to do his homework. His mother says that at home he has been like that since the last 2 to 3 years, but now she is concerned because of the difficulties he is experiencing at school as well. After obtaining his medical history, examination, and getting response from parents and teachers--using Vanderbuilt Assessment Scales--the paediatrician diagnoses him to have attention deficit hyperactivity disorder. Besides behavioural interventions, he considers medications for his management. The paediatrician is debating the merits of performing electrocardiogram and/or referring the boy to a cardiologist before starting stimulant medications. If you were caring for this patient, how would you proceed? PMID- 26278962 TI - Role of cholesterol crystals in atherosclerosis is unmasked by altering tissue preparation methods. AB - Standard tissue preparation for light and scanning electron microscopy (SEM) uses ethanol as a dehydrating agent but that can also dissolve cholesterol crystals (CC) leaving behind empty tissue imprints or "clefts". Cholesterol crystals may contribute to plaque rupture by their sharp tips that can tear membranes and trigger inflammation. Therefore, use of ethanol in tissue processing can mask the pathological role of CC. Here we evaluated the amount of cholesterol dissolved from CC with single and complete series of standard graded ethanol concentrations (25-100%) used in tissue preparation. Also, solubility of CC in ethanol at physiological levels was measured. Furthermore, we compared the effect of ethanol on CC in fresh human atherosclerotic plaques to matched segments dehydrated using vacuum (-1 atm, 12h). Tissue crystal density ranging from 0 to +3 was measured semi-quantitatively by SEM. For CC exposed to 25% and 100% ethanol for 10 min each, 0.38% and 95% of CC were dissolved respectively. Also, increase in CC solubility was significant at physiological levels of ethanol (0.16%) compared to water (43.4 +/- 18.0 ng/mL vs. 30.9 +/- 13.9 ng/mL; p < 0.05). We speculate that this could represent a potential mechanism of cardio-protective effects of alcohol consumption. In atherosclerotic plaques, CC density was lower in ethanol vs. saline treatment (+1.2 vs. +2.8; P < 0.01) with visible dissolving noted by SEM. Ethanol has been used for centuries in tissue preparation for microscopy. Here we demonstrate how current tissue preparation methods greatly alter histological findings with SEM by masking the potential mechanism of plaque rupture. PMID- 26278961 TI - Label-free quantitative phosphoproteomics with novel pairwise abundance normalization reveals synergistic RAS and CIP2A signaling. AB - Hyperactivated RAS drives progression of many human malignancies. However, oncogenic activity of RAS is dependent on simultaneous inactivation of protein phosphatase 2A (PP2A) activity. Although PP2A is known to regulate some of the RAS effector pathways, it has not been systematically assessed how these proteins functionally interact. Here we have analyzed phosphoproteomes regulated by either RAS or PP2A, by phosphopeptide enrichment followed by mass-spectrometry-based label-free quantification. To allow data normalization in situations where depletion of RAS or PP2A inhibitor CIP2A causes a large uni-directional change in the phosphopeptide abundance, we developed a novel normalization strategy, named pairwise normalization. This normalization is based on adjusting phosphopeptide abundances measured before and after the enrichment. The superior performance of the pairwise normalization was verified by various independent methods. Additionally, we demonstrate how the selected normalization method influences the downstream analyses and interpretation of pathway activities. Consequently, bioinformatics analysis of RAS and CIP2A regulated phosphoproteomes revealed a significant overlap in their functional pathways. This is most likely biologically meaningful as we observed a synergistic survival effect between CIP2A and RAS expression as well as KRAS activating mutations in TCGA pan-cancer data set, and synergistic relationship between CIP2A and KRAS depletion in colony growth assays. PMID- 26278964 TI - Diabetes Care Provided to Children Displaced by Hurricane Katrina. AB - OBJECTIVE: Although previous studies have examined the impact of Hurricane Katrina on adults with diabetes, less is known about the effects on children with diabetes and on those displaced by the storm. We analyzed individual-level enrollment and utilization data of children with diabetes who were displaced from Louisiana and were enrolled in the Texas Medicaid Hurricane Katrina emergency waiver (TexKat). METHODS: We compared the utilization and outcomes of children displaced from Louisiana with those of children who lived in areas less affected by Hurricane Katrina. Data from both before and after the storm were used to calculate difference-in-difference estimates of the effects of displacement on the children. We analyzed 4 diabetes management procedures (glycated hemoglobin [HbA1C] tests, eye exams, microalbumin tests, and thyroid tests) and a complication from poor diabetes management (diabetic ketoacidosis). RESULTS: Children enrolled in the waiver generally did not experience a decrease in care relative to the control group while the waiver program was in effect. After the waiver ended, however, we observed a drop in care and an increase in complications relative to the control group. CONCLUSIONS: Although the waiver appeared to have been largely successful immediately following Katrina, future waivers may be improved by ensuring that enrollees continue to receive care after the waivers expire. PMID- 26278963 TI - Discovery of a drug targeting microenvironmental support for lymphoma cells by screening using patient-derived xenograft cells. AB - Cell lines have been used for drug discovery as useful models of cancers; however, they do not recapitulate cancers faithfully, especially in the points of rapid growth rate and microenvironment independency. Consequently, the majority of conventional anti-cancer drugs are less sensitive to slow growing cells and do not target microenvironmental support, although most primary cancer cells grow slower than cell lines and depend on microenvironmental support. Here, we developed a novel high throughput drug screening system using patient-derived xenograft (PDX) cells of lymphoma that maintained primary cancer cell phenotype more than cell lines. The library containing 2613 known pharmacologically active substance and off-patent drugs were screened by this system. We could find many compounds showing higher cytotoxicity than conventional anti-tumor drugs. Especially, pyruvinium pamoate showed the highest activity and its strong anti tumor effect was confirmed also in vivo. We extensively investigated its mechanism of action and found that it inhibited glutathione supply from stromal cells to lymphoma cells, implying the importance of the stromal protection from oxidative stress for lymphoma cell survival and a new therapeutic strategy for lymphoma. Our system introduces a primary cancer cell phenotype into cell-based phenotype screening and sheds new light on anti-cancer drug development. PMID- 26278965 TI - CmpacC regulates mycoparasitism, oxalate degradation and antifungal activity in the mycoparasitic fungus Coniothyrium minitans. AB - The PacC/Rim101 pH-responsive transcription factor is an important pathogenicity element for many plant-pathogenic fungi. In this study, we investigated the roles of a PacC homologue, CmpacC, in the mycoparasitic fungus Coniothyrium minitans. CmpacC was confirmed to have the transcriptional activation activity by the transcriptional activation test in Saccharomyces cerevisiae. Disruption of CmpacC resulted in impaired fungal responses to ambient pH. Compared to the wild-type, the CmpacC-disruption mutant DeltaCmpacC-29 was significantly suppressed for activities of chitinase and beta-1,3-glucanase at pH 5 and 7, consistent with reduced expression levels of Cmch1 and Cmg1 coding for the two enzymes respectively. However, the mutant displayed acidity-mimicking phenotypes such as improved oxalate degradation and increased antifungal activity at pH 6 or higher. Improved efficacy in oxalate degradation by DeltaCmpacC-29 was consistent with the enhanced expression level of Cmoxdc1 coding for oxalate decarboxylase. CmpacC transcriptional activation of Cmch1 and Cmg1 and repression of Cmoxdc1 were verified by the presence of the PacC/Rim101 consensus binding-motifs in gene promoter regions and by the promoter DNA-binding assays. This study suggests that CmpacC plays an activator role in regulation of C. minitans mycoparasitism, whereas plays a repressor role in regulation of oxalate degradation and possibly antifungal activity of C. minitans. PMID- 26278966 TI - Hemostasis and thrombosis beyond biochemistry: roles of geometry, flow and diffusion. AB - An important trend in the modern concept of blood coagulation is the growing agreement that, in order to understand regulation of coagulation in vivo and disorders of its function, it is essential to take into account its spatial heterogeneity, diffusion, and flow. In a way, this suggests that the idea of the "coagulation cascade" itself becomes increasingly misleading because there is no such place in an organism where reactions of this cascade really co-exist: activation, propagation and termination of coagulation are regulated by different subsets of chemical reactions that have different spatial localization and depend on cofactors expressed by different cell types in different tissues, so that only diffusion and flow can link these distinct "compartments" together into the one functional system. Here we review the last two decades of evidence obtained from in vitro, in vivo and computational systems biology approaches. When combined, the data comprise into an adequately comprehensive picture of the spatial regulation and organization of blood coagulation. In addition to the basic insights into the regulatory mechanisms, these approaches provided interesting results in the fields of coagulation diagnostics and other applications. Finally, the remaining unresolved and conflicting issues in the spatiotemporal regulation of coagulation are discussed. PMID- 26278967 TI - A family having type 2B von Willebrand disease with a novel VWF p.R1308S mutation: Detection of characteristic platelet aggregates on peripheral blood smears as the key aspect of diagnosis. AB - Type 2B von Willebrand disease (VWD) is frequently associated with distinct platelet morphology. Here we present a familial case of type 2B VWD with a novel VWF mutation (p.R1308S), which caused neonatal thrombocytopenia. The mother had been treated for refractory immune thrombocytopenia (ITP) for more than 20years. The most important hematological features of this case were large platelets and platelet aggregates detected on peripheral blood smears. Hemostatic tests showed enhanced ristocetin-induced platelet agglutination at low-ristocetin concentrations, absence of high-molecular weight von Willebrand factor (VWF) multimers, and low VWF cofactor activity/antigen ratio. In patients with intractable ITP, family history of ITP and consecutive neonatal thrombocytopenia, the differential diagnosis of congenital thrombocytopenia is mandatory. For this purpose, the identification of large platelets and platelet aggregates on peripheral blood smears is the key aspect of type 2B VWD diagnosis. PMID- 26278968 TI - Quantum Simulator for Transport Phenomena in Fluid Flows. AB - Transport phenomena still stand as one of the most challenging problems in computational physics. By exploiting the analogies between Dirac and lattice Boltzmann equations, we develop a quantum simulator based on pseudospin-boson quantum systems, which is suitable for encoding fluid dynamics transport phenomena within a lattice kinetic formalism. It is shown that both the streaming and collision processes of lattice Boltzmann dynamics can be implemented with controlled quantum operations, using a heralded quantum protocol to encode non unitary scattering processes. The proposed simulator is amenable to realization in controlled quantum platforms, such as ion-trap quantum computers or circuit quantum electrodynamics processors. PMID- 26278969 TI - Quantitative T2 mapping after reperfusion therapy in patients with acute myocardial infarction: A comparison with late gadolinium enhancement and cine MR imaging. AB - PURPOSE: This study evaluates myocardial edema by quantitative T2 mapping in patients with acute myocardial infarction (AMI) and compares the lateral extent of myocardial edema with those of infarcted and dysfunctional myocardium. MATERIALS AND METHODS: Cardiac magnetic resonance images (MRIs) of 31 patients (M:F=29:2, mean age: 52.5+/-10.8years) with AMI were reviewed. On cine-MRI, all short axis images of the left ventricle (LV) were divided into 60 sectors. The regional wall motion of each sector was calculated as follows: systolic wall thickening (SWT, %)=[(LV wall thicknessES-LV wall thicknessED)/LV wall thicknessED]*100. Dysfunctional myocardium was defined as sectors with decreased SWT lower than 40%. On LGE-images, myocardial infarction was defined as an area of hyper-enhancement more than 5 SDs from the remote myocardium. On T2 map, myocardial edema was defined as an area in which T2 values were at least 2 SDs higher than those from remote myocardium. The lateral extents of infarcted myocardium, myocardial edema, and dysfunctional myocardium were calculated as the percentage of central angles ((central angle of the involved myocardium/360)*100 (%)) and then compared. RESULTS: The lateral extent of myocardial edema was slightly larger than that of infarcted myocardium (37.4+/-13.3% vs. 35+/-12.9%, p<0.01). The lateral extent of dysfunctional myocardium (50.6+/-15.3%) was significantly larger than that of infarcted myocardium or myocardial edema (p<0.001). CONCLUSIONS: The lateral extent of myocardial edema beyond the infarcted myocardium might be narrow, but the dysfunctional myocardium could be significantly larger than myocardial edema, suggesting stunned myocardium without edema. PMID- 26278970 TI - Acoustic-integrated dynamic MR imaging for a patient with obstructive sleep apnea. AB - Obstructive sleep apnea syndrome (OSAS) is caused by multi-level upper airway obstruction. Anatomic changes at the sites of obstruction may modify the physical or acoustic properties of snores. The surgical success of OSA depends upon precise localization of obstructed levels. We present a case of OSAS who received simultaneous dynamic MRI and snore acoustic recordings. The synchronized image and acoustic information successfully characterize the sites of temporal obstruction during sleep-disordered breathing events. PMID- 26278971 TI - Application of Organ Clearance to Estimation of the In Vivo Hepatic Extraction Ratio. AB - Organ clearance, which has been derived from the organ blood flow and extraction ratio (E), has been extensively used by clinical pharmacologists to explain the pharmacokinetics of many drugs in health and disease. For example, the extent of hepatic clearance or E (Eh) of drugs would determine their response to changes in the liver blood flow and/or activities of the metabolizing enzymes. Although Eh may be obtained directly by cannulating internal blood vessels, the method is invasive. Therefore, indirect methods have been used to estimate Eh from the peripheral blood concentration-time data after intravascular administration of drugs. Additionally, these indirect methods require an estimate of the liver blood flow in the patients or animals. However, some investigators use plasma concentrations and/or liver plasma flow for the estimation of Eh, which could potentially result in significant errors. It is shown here that when plasma concentrations are used along with liver blood flow, an overestimation or underestimation of the true value will result if the blood: plasma concentration (B:P) ratio is >1 or < 1, respectively, with the estimated Eh being different from the true value by a factor equal to the B:P ratio. On the other hand, the use of plasma concentrations and plasma liver flow will always result in an overestimation of the true Eh unless the drug does not penetrate the red blood cells. It is concluded that for the accurate estimation of Eh from the in vivo data, the blood concentration and blood flow should be used. PMID- 26278972 TI - Enzyme function is regulated by its localization. AB - To better understand how enzyme localization affects enzyme activity we studied the cellular localization of the glycosyltransferase MurG, an enzyme necessary for cell wall synthesis at the spore during sporulation in the bacterium Bacillus subtilis. During sporulation MurG was gradually enriched to the membrane at the forespore and point mutations in a MurG helical domain disrupting its localization to the membrane caused severe sporulation defects, but did not affect localization nor caused detectable defects during exponential growth. We found that this localization is dependent on the phospholipid cardiolipin, as in strains where the cardiolipin-synthesizing genes were deleted, MurG levels were diminished at the forespore. Furthermore, in this cardiolipin-less strain, MurG localization during sporulation was rescued by external addition of purified cardiolipin. These results support localization as a critical factor in the regulation of proper enzyme function and catalysis. PMID- 26278973 TI - Molecular docking study of natural alkaloids as multi-targeted hedgehog pathway inhibitors in cancer stem cell therapy. AB - Cancer is responsible for millions of deaths throughout the world every year. Increased understanding as well as advancements in the therapeutic aspect seems suboptimal to restrict the huge deaths associated with cancer. The major cause responsible for this is high resistance as well as relapse rate associated with cancers. Several evidences indicated that cancer stem cells (CSC) are mainly responsible for the resistance and relapses associated with cancer. Furthermore, agents targeting a single protein seem to have higher chances of resistance than multitargeting drugs. According to the concept of network model, partial inhibition of multiple targets is more productive than single hit agents. Thus, by fusing both the premises that CSC and single hit anticancer drugs, both are responsible for cancer related resistances and screened alkaloids for the search of leads having CSC targeting ability as well as the capability to modulating multiple target proteins. The in silico experimental data indicated that emetine and cortistatin have the ability to modulate hedgehog (Hh) pathway by binding to sonic hedgehog (Hh), smoothened (Smo) and Gli protein, involved in maintenance CSCs. Furthermore, solamargine, solasonine and tylophorine are also seems to be good lead molecules targeting towards CSCs by modulating Hh pathway. Except solamargine and solasonine, other best lead molecules also showed acceptable in silico ADME profile. The predicted lead molecules can be suitably modified to get multitargeting CSC targeting agent to get rid of associate resistances. PMID- 26278974 TI - Reconstructing gene regulatory networks from knock-out data using Gaussian Noise Model and Pearson Correlation Coefficient. AB - A gene regulatory network (GRN) is a large and complex network consisting of interacting elements that, over time, affect each other's state. The dynamics of complex gene regulatory processes are difficult to understand using intuitive approaches alone. To overcome this problem, we propose an algorithm for inferring the regulatory interactions from knock-out data using a Gaussian model combines with Pearson Correlation Coefficient (PCC). There are several problems relating to GRN construction that have been outlined in this paper. We demonstrated the ability of our proposed method to (1) predict the presence of regulatory interactions between genes, (2) their directionality and (3) their states (activation or suppression). The algorithm was applied to network sizes of 10 and 50 genes from DREAM3 datasets and network sizes of 10 from DREAM4 datasets. The predicted networks were evaluated based on AUROC and AUPR. We discovered that high false positive values were generated by our GRN prediction methods because the indirect regulations have been wrongly predicted as true relationships. We achieved satisfactory results as the majority of sub-networks achieved AUROC values above 0.5. PMID- 26278975 TI - Placental 11B-Hydroxysteroid Dehydrogenase Type 2 mRNA Levels in Intrauterine Growth Restriction versus Small-for-Gestational-Age Fetuses. AB - INTRODUCTION: The objective of this study was to evaluate placental 11B hydroxysteroid dehydrogenase type 2 (11B-HSD-2) mRNA levels in intrauterine growth-restricted fetuses (IUGR) as compared with small-for-gestational-age (SGA) fetuses according to clinical criteria. MATERIAL AND METHODS: Placental levels of 11B-HSD-2 mRNA levels were measured in SGA (birth weight <10th centile) and gestational-age-matched, appropriate-for-gestational-age (AGA) births. SGA was classified as IUGR (birth weight <3rd centile or <10th percentile with abnormal uterine artery Doppler or cerebroplacental ratio) or non-IUGR SGA. After RNA extraction, mRNA levels were determined by reverse transcription and quantitative PCR. RESULTS: A total of 38 placentas were analyzed (20 AGA and 18 SGA). Among the SGA pregnancies, 13 qualified as IUGR. The activity of 11B-HSD-2 in IUGR pregnancies [0.105 (SD 0.328)] was significantly reduced compared to non-IUGR SGA [0.304 (SD 0.261); p = 0.018] and AGA [0.294 (SD 0.328); p = 0.001]. These differences remained significant after adjusting for potential confounders (such as smoking or maternal cortisol levels). Activity levels did not significantly differ between non-IUGR SGA and AGA. DISCUSSION: IUGR fetuses had reduced 11B-HSD 2 activity in comparison with SGA and normally grown fetuses. This finding provides opportunities to develop new placental biomarkers for the phenotypic characterization of fetal smallness. PMID- 26278976 TI - Challenges in the Biomedical Research Enterprise in the 21st century: Antecedents in the writings of David Triggle. AB - David Triggle's career as an educator, researcher, essayist and ethicist in many ways has paralleled the post WWII emergence of the "biomedical research ecosystem" that originated in the concept of the "Endless Frontier". In the ensuing 70 years biomedical research has irreparably changed the nature of society with vaccines, the birth control pill and new generations of drugs and biologics to treat infections, sexually transmitted diseases, psychiatric disorders and cardiovascular diseases. These have led to a shift in the population demographic to the elderly and the chronically sick leading to major issues in the provision of effective and affordable healthcare for much of the world's population. In the present article, in addition to providing a brief biography and an appreciation of David Triggle's contributions to science, the authors expand on three topics in which he has had a major interest: improving the quality, reproducibility and relevance of basic biomedical research; declining career opportunities for graduates in an era of decreased funding-the end of the "Endless Frontier"; and the dynamic between the provision for universal healthcare and the dysfunctional, wasteful and politicized systems of the current medical-industrial complex in delivering healthcare. PMID- 26278977 TI - alpha5-Integrin-mediated cellular signaling contributes to the myogenic response of cerebral resistance arteries. AB - The myogenic response of resistance arterioles and small arteries involving constriction in response to intraluminal pressure elevation and dilation on pressure reduction is fundamental to local blood flow regulation in the microcirculation. Integrins have garnered considerable attention in the context of initiating the myogenic response, but evidence indicative of mechanotransduction by integrin adhesions, for example established changes in tyrosine phosphorylation of key adhesion proteins, has not been obtained to substantiate this interpretation. Here, we evaluated the role of integrin adhesions and associated cellular signaling in the rat cerebral arterial myogenic response using function-blocking antibodies against alpha5beta1-integrins, pharmacological inhibitors of focal adhesion kinase (FAK) and Src family kinase (SFK), an ultra-high-sensitivity western blotting technique, site-specific phosphoprotein antibodies to quantify adhesion and contractile filament protein phosphorylation, and differential centrifugation to determine G-actin levels in rat cerebral arteries at varied intraluminal pressures. Pressure-dependent increases in the levels of phosphorylation of FAK (FAK-Y397, Y576/Y577), SFK (SFK Y416; Y527 phosphorylation was reduced), vinculin-Y1065, paxillin-Y118 and phosphoinositide-specific phospholipase C-gamma1 (PLCgamma1)-Y783 were detected. Treatment with alpha5-integrin function-blocking antibodies, FAK inhibitor FI-14 or SFK inhibitor SU6656 suppressed the changes in adhesion protein phosphorylation, and prevented pressure-dependent phosphorylation of the myosin targeting subunit of myosin light chain phosphatase (MYPT1) at T855 and 20kDa myosin regulatory light chains (LC20) at S19, as well as actin polymerization that are necessary for myogenic constriction. We conclude that mechanotransduction by integrin adhesions and subsequent cellular signaling play a fundamental role in the cerebral arterial myogenic response. PMID- 26278978 TI - Simplified dietary acute tryptophan depletion: effects of a novel amino acid mixture on the neurochemistry of C57BL/6J mice. AB - BACKGROUND: Diet and nutrition can impact on the biological processes underpinning neuropsychiatric disorders. Amino acid (AA) mixtures lacking a specific neurotransmitter precursor can change the levels of brain serotonin (5 HT) or dopamine (DA) in the central nervous system. The availability of these substances within the brain is determined by the blood-brain barrier (BBB) that restricts the access of peripheral AA into the brain. AA mixtures lacking tryptophan (TRP) compete with endogenous TRP for uptake into the brain across the BBB, which in turn leads to a decrease in central nervous 5-HT synthesis. OBJECTIVE: The present study compared the effects of a simplified acute tryptophan depletion (SATD) mixture in mice on blood and brain serotonergic and dopaminergic metabolites to those of a commonly used acute tryptophan depletion mixture (ATD Moja-De) and its TRP-balanced control (BAL). DESIGN: The SATD formula is composed of only three large neutral AAs: phenylalanine (PHE), leucine (LEU), and isoleucine (ILE). BAL, ATD Moja-De, or SATD formulas were delivered to adult male C57BL/6J mice by gavage. TRP, monoamines, and their metabolites were quantified in blood and brain regions (hippocampus, frontal cortex, amygdala, caudate putamen, and nucleus accumbens). RESULTS: Both ATD Moja-De and SATD significantly decreased levels of serum and brain TRP, as well as brain 5-HIAA and 5-HT compared with BAL. SATD reduced HVA levels in caudate but did not alter total DA levels or DOPAC. SATD decreased TRP and serotonergic metabolites comparably to ATD Moja-De administration. CONCLUSION: A simplified and more palatable combination of AAs can manipulate serotonergic function and might be useful to reveal underlying monoamine-related mechanisms contributing to different neuropsychiatric disorders. PMID- 26278979 TI - Automatic estimation and correction of anisotropic magnification distortion in electron microscopes. AB - We demonstrate a significant anisotropic magnification distortion, found on an FEI Titan Krios microscope and affecting magnifications commonly used for data acquisition on a Gatan K2 Summit detector. We describe a program (mag_distortion_estimate) to automatically estimate anisotropic magnification distortion from a set of images of a standard gold shadowed diffraction grating. We also describe a program (mag_distortion_correct) to correct for the estimated distortion in collected images. We demonstrate that the distortion present on the Titan Krios microscope limits the resolution of a set of rotavirus VP6 images to ~7 A, which increases to ~3 A following estimation and correction of the distortion. We also use a 70S ribosome sample to demonstrate that in addition to affecting resolution, magnification distortion can also interfere with the classification of heterogeneous data. PMID- 26278980 TI - CTFFIND4: Fast and accurate defocus estimation from electron micrographs. AB - CTFFIND is a widely-used program for the estimation of objective lens defocus parameters from transmission electron micrographs. Defocus parameters are estimated by fitting a model of the microscope's contrast transfer function (CTF) to an image's amplitude spectrum. Here we describe modifications to the algorithm which make it significantly faster and more suitable for use with images collected using modern technologies such as dose fractionation and phase plates. We show that this new version preserves the accuracy of the original algorithm while allowing for higher throughput. We also describe a measure of the quality of the fit as a function of spatial frequency and suggest this can be used to define the highest resolution at which CTF oscillations were successfully modeled. PMID- 26278981 TI - Multi-scale simulation of plant stem reinforcement by brachysclereids: A case study in apple fruit peduncles. AB - Sclereid formation in addition to or in gaps of fragmented fibre rings is common in dicotyledonous plant stems. Whether this sclereid formation is force-triggered remains open so far. In fruit peduncles of several Malus species as modified plant stems, for example, the persistent fibre ring is displaced to the centre by formation of cortex parenchyma during growth. Parenchyma cells subsequently differentiate into an additional layer of brachysclereids, previously interpreted as an adaptation to continuously rising fruit loads. The present study pursues a multi-scale numerical modelling approach, to verify the important effect for different cellular architectures in both sclerenchyma categories on the stiffness of these tissues and the entire peduncle. First, different material properties are simulated analogue to plant tissues on the basis of three cell types. A regular three-dimensional and a random Voronoi microstructure combined with various mechanical cell wall parameters are applied. Using homogenisation simulations based on HILL's principle, numerical calculations predict a lower effective homogenised tissue stiffness of isodiametric brachysclereids compared to those of fibres, confirming experimentally obtained data from Malus fruit peduncles. Furthermore, a curved peduncle model with a complex arrangement of different material layers is generated. Diverse material sets are tested under three representative loadings, using an adaptive diffuse domain approach (AMDiS). The model explains the function of sclereids as considerable contributors to the stiffness against bending and tensile deformations, as well as torsion, especially in consequence of superimposed load conditions in the case of a curved plant stem. PMID- 26278982 TI - Polyglucosan storage myopathies. AB - Polyglucosan is an amylopectin-like polysaccharide associated with defective glycogen metabolism and, unlike normal glycogen, it is to some extent resistant to alpha-amylase digestion. It also has a characteristic fibrillar appearance under the electron microscope. Polyglucosan may aggregate into dense inclusions known as polyglucosan bodies. Its accumulation can be found in various tissues to some degree in normal ageing, but it is also the hallmark of some diseases associated with defects in glycogen metabolism. These diseases frequently involve both skeletal and cardiac muscle tissue, causing myopathy with muscle weakness and wasting, and cardiomyopathy with arrhythmia, conduction block, and cardiac failure. Mutations in eight human genes are known to be associated with polyglucosan storage involving muscle, namely GYG1, GBE1, RBCK1 (HOIL-1), PFKM, EPM2A, EPM2B (NHLRC1), PRDM8, and PRKAG2. There is also a common equine polysaccharide storage myopathy belonging to this group of diseases involving the GYS1 gene. The pathogenic mechanisms that cause the abnormal glycogen accumulation appearing as polyglucosan have been studied in some of these diseases. In most cases the pathogenesis is largely unknown. In this review, we summarize the polyglucosan storage diseases from a clinical, morphological, and genetic standpoint. We also identify some important similarities and differences regarding the morphological appearance of polyglucosan accumulation and discuss pathogenic pathways. PMID- 26278983 TI - Getting a handle on glycogen synthase - Its interaction with glycogenin. AB - Glycogen is a polymer of glucose that serves as a major energy reserve in eukaryotes. It is synthesized through the cooperative action of glycogen synthase (GS), glycogenin (GN) and glycogen branching enzyme. GN initiates the first enzymatic step in the glycogen synthesis process by self glucosylation of a short 8-12 glucose residue primer. After interacting with GN, GS then extends this sugar primer to form glycogen particles of different sizes. We discuss recent developments in the structural biology characterization of GS and GN enzymes, which have contributed to a better understanding of how the two proteins interact and how they collaborate to synthesize glycogen particles. PMID- 26278985 TI - [Clinical and paraclinical follow-up after radiotherapy for head and neck cancer]. AB - Head and neck cancer management often involves heavy multimodal treatments including radiotherapy. Despite the improvement of intensity-modulated radiation therapy, acute and late toxicities remain important. After such treatment, patients have to face different potential problems, depending on the post therapeutic delay. In this way, short-term follow-up permits to appreciate the healing of acute toxicities and response to treatment. Long-term follow-up aims to recognize second primitive tumours and distant failure, and to detect and manage late toxicities. Medical and psychosocial supportive cares are essential, even after several years of complete remission. The objective of this article is to review the modalities of short-term and long-term follow-up of patients who receive a radiotherapy for head and neck cancer. PMID- 26278984 TI - Glycogen phosphorylation and Lafora disease. AB - Covalent phosphorylation of glycogen, first described 35 years ago, was put on firm ground through the work of the Whelan laboratory in the 1990s. But glycogen phosphorylation lay fallow until interest was rekindled in the mid 2000s by the finding that it could be removed by a glycogen-binding phosphatase, laforin, and that mutations in laforin cause a fatal teenage-onset epilepsy, called Lafora disease. Glycogen phosphorylation is due to phosphomonoesters at C2, C3 and C6 of glucose residues. Phosphate is rare, ranging from 1:500 to 1:5000 phosphates/glucose depending on the glycogen source. The mechanisms of glycogen phosphorylation remain under investigation but one hypothesis to explain C2 and perhaps C3 phosphate is that it results from a rare side reaction of the normal synthetic enzyme glycogen synthase. Lafora disease is likely caused by over accumulation of abnormal glycogen in insoluble deposits termed Lafora bodies in neurons. The abnormality in the glycogen correlates with elevated phosphorylation (at C2, C3 and C6), reduced branching, insolubility and an enhanced tendency to aggregate and become insoluble. Hyperphosphorylation of glycogen is emerging as an important feature of this deadly childhood disease. PMID- 26278986 TI - [Radiotherapy for gliomas in adults: What are the stakes of the follow-up?]. AB - Linked to the difference of prognosis, the terms and conditions of the follow-up of low-grade and high-grade gliomas treated by irradiation differ highly. Patients treated for a low-grade glioma have prolonged survival. In this case, monitoring of toxicities linked to the treatment is a major objective. Opportunistic infections and depression are corticosteroids side effects widely underestimated. Radionecrosis search and differentiation with recurrent disease are done by MRI. Perfusion and spectroscopy showing a choline/creatine ratio increase are in favour of disease recurrence. Cognitive status and quality of life must be evaluated during the follow-up. They have to be evaluated by adapted scales. Cognitive rehabilitation improves interestingly the post-treatment cognitive status. Pseudoprogression rates for high-grade gliomas are near 20%. MRI is the benchmark imaging for its diagnosis. Diffusion weight imaging and spectroscopy are actually the most interesting techniques. PMID- 26278987 TI - [Current status of hypofractionated external beam radiotherapy for early-stage breast cancer]. AB - The benefits of adjuvant radiotherapy following lumpectomy for early-stage breast cancer are well established. The most widely used method consists of roughly twenty-five fractions of whole-breast irradiation. In recent years, there has been a growing trend towards hypofractionated external beam radiotherapy regimens. Many of these techniques have been shown to be equivalent in terms of tumor control and cosmetic results while minimizing inconvenience and costs both to the patient and health care system. Here, we present the various hypofractionation modalities, patient selection criteria, consensus guideline recommendations and a look at future indications. PMID- 26278988 TI - Hypofractionated radiation therapy for prostate cancer: The McGill University Health Center experience. AB - PURPOSE: In 2002, at the McGill University Health Centre, we began a program of hypofractionated radiotherapy for patients with low risk prostate cancer as an alternative to conventionally fractionated radiotherapy. MATERIAL AND METHODS: Our initial hypofractionation regimen was 66 Gy given in 22 fractions, prescribed to the isocenter, delivered with 3D-conformal radiotherapy plan. The clinical target volume was the prostate gland and the planning target volume consisted of the clinical target volume plus a 7-mm margin in all directions. Hormonal therapy was not given to any patient. RESULTS: The long-term results for this group of patients confirmed the feasibility, good tolerance and excellent disease control of the regimen with the extra-benefit of being convenient to both patients and the health system by shortening treatment duration. The outcomes of this approach stimulated us to use hypofractionation in patients with intermediate-risk. Analysis of 100 intermediate-risk patients receiving our hypofractionated radiotherapy regimen (no hormones) shows, at median follow-up of 75 months, 8 year biochemical recurrence free and cancer specific survival rates of 90% and 95%, respectively, with acceptable toxicity. DISCUSSION: Our technique changed from 3D to intensity modulated radiotherapy with the dose adjusted to 60 Gy in 20 fractions. Lastly, we have expanded the program to high-risk patients where IMRT treatments are given to the pelvic nodes (44 Gy in 20 fractions) with a simultaneous integrated boost delivery to the prostate (60 Gy in the same 20 fractions). Our long-term results have shown that moderate hypofractionated radiotherapy for prostate cancer is safe and provides good tumor control comparable to high-dose conventionally fractionated radiotherapy. This hypofractionated regimen has been routinely used in our institution. PMID- 26278989 TI - [Surveillance after prostate cancer radiotherapy: Evaluation and management of toxicity and relapse]. AB - Prostate cancer is the most frequent cancer among European males with a high survival rate. The economic impact of treatments and follow-up are significant. The objectives of the follow-up after prostate radiotherapy is multiple: diagnosis and treatment of side-effects, early detection of biochemical recurrence, with the aim of proposing a second local treatment to improve quality of life or overall survival and feedback of the treatment results to better inform patients at the beginning of the disease. This article reports incidence of main side-effects (digestive, urinary and sexual) with their treatments and guidelines for clinical and biological follow-up with strategies of imaging studies and salvage treatments. PMID- 26278990 TI - [Organ preserving strategies for rectal cancer treatment]. AB - For rectal cancers, the current standard of care consists of chemoradiation followed by radical surgery with total mesorectal excision. Oncologic results are good, especially regarding local recurrence rates, but at the cost of high morbidity rates and poor anorectal, urinary and sexual function results. Since chemoradiation yields 15 to 25% pathological complete response, the role of radical surgery is questioned for patients presenting with good response after chemoradiation and two organ preservation strategies have been offered: watch and wait strategy and local excision strategy. The aim of this review is to give the results of organ preservation after chemoradiotherapy series and to highlight different questions regarding initial patient's selection, complete clinical response definition, risk of mesorectal nodal involvement, follow-up modalities as well as oncologic and functional results. PMID- 26278991 TI - [Implementing new technology in radiation oncology: The French agency for nuclear safety (ASN) report]. AB - In August 2013, the French nuclear safety agency (ASN) requested the permanent group of experts in radiation protection in medicine (GPMED) to propose recommendations on the implementation of new technology and techniques in radiation oncology. These recommendations were finalized in February 2015 by the GPMED. In April 2015, the ASN sent a letter to the French ministry of health (DGS/DGOS), and its national health agencies (ANSM, INCa, HAS). In these letters, ASN proposed that, from the 12 recommendations made by the GPMED, an action plan should be established, whose control could be assigned to the French national cancer institute (INCa), as a pilot of the national committee for radiotherapy and that this proposal has to be considered at the next meeting of the national committee of radiotherapy. PMID- 26278992 TI - Micro-intestinal robot with wireless power transmission: design, analysis and experiment. AB - BACKGROUND: Video capsule endoscopy is a useful tool for noninvasive intestinal detection, but it is not capable of active movement; wireless power is an effective solution to this problem. METHODS: The research in this paper consists of two parts: the mechanical structure which enables the robot to move smoothly inside the intestinal tract, and the wireless power supply which ensures efficiency. First, an intestinal robot with leg architectures was developed based on the Archimedes spiral, which mimics the movement of an inchworm. The spiral legs were capable of unfolding to an angle of approximately 155 degrees , which guaranteed stability of clamping, consistency of surface pressure, and avoided the risk of puncturing the intestinal tract. Secondly, the necessary power to operate the robot was far beyond the capacity of button batteries, so a wireless power transmission (WPT) platform was developed. The design of the platform focused on power transfer efficiency and frequency stability. In addition, the safety of human tissue in the alternating electromagnetic field was also taken into consideration. Finally, the assembled robot was tested and verified with the use of the WPT platform. RESULTS: In the isolated intestine, the robot system successfully traveled along the intestine with an average speed of 23 mm per minute. The obtained videos displayed a resolution of 320 * 240 and a transmission rate of 30 frames per second. The WPT platform supplied up to 500 mW of energy to the robot, and achieved a power transfer efficiency of 12%. CONCLUSION: It has been experimentally verified that the intestinal robot is safe and effective as an endoscopy tool, for which wireless power is feasible. Proposals for further improving the robot and wireless power supply are provided later in this paper. PMID- 26278993 TI - Singlet oxygen photogeneration from X-O2 van der Waals complexes: double spin flip vs. charge-transfer mechanism. AB - The channel of singlet oxygen O2((1)Deltag) photogeneration from van der Waals complexes of oxygen X-O2 has been investigated to discriminate between two possible mechanisms based on charge-transfer (CT) or double spin-flip (DSF) transitions. The results obtained in this work for complexes with X = ethylene C2H4, 1,3-butadiene C4H6, deuterated methyl iodide CD3I, benzene C6H6 and water H2O and for those investigated previously indicate the DSF mechanism as a source of singlet oxygen. The formation of O2((1)Deltag) is observed only when the energy of exciting quantum is sufficient for DSF transition. Universally detected low vibrational excitation of O2((1)Deltag) arising in the photodissociation of van der Waals complexes X-O2 indicates the DSF mechanism as its source. For complex of ethylene C2H4-O2ab initio calculations of vertical energy DeltaE(vert) for DSF and CT transitions have been carried out. The positive results of singlet oxygen formation from C2H4-O2 can be explained by the DSF but not by the CT mechanism. PMID- 26278994 TI - Optimization of hydrolysis and volatile fatty acids production from sugarcane filter cake: Effects of urea supplementation and sodium hydroxide pretreatment. AB - Different methods for optimization the anaerobic digestion (AD) of sugarcane filter cake (FC) with a special focus on volatile fatty acids (VFA) production were studied. Sodium hydroxide (NaOH) pretreatment at different concentrations was investigated in batch experiments and the cumulative methane yields fitted to a dual-pool two-step model to provide an initial assessment on AD. The effects of nitrogen supplementation in form of urea and NaOH pretreatment for improved VFA production were evaluated in a semi-continuously operated reactor as well. The results indicated that higher NaOH concentrations during pretreatment accelerated the AD process and increased methane production in batch experiments. Nitrogen supplementation resulted in a VFA loss due to methane formation by buffering the pH value at nearly neutral conditions (~ 6.7). However, the alkaline pretreatment with 6g NaOH/100g FCFM improved both the COD solubilization and the VFA yield by 37%, mainly consisted by n-butyric and acetic acids. PMID- 26278995 TI - Behavior of CMPCs in unidirectional constrained and stress-free 3D hydrogels. AB - Cardiomyocyte progenitor cells (CMPCs) are a candidate cell source for cardiac regenerative therapy. However, like other stem cells, after transplantation in the heart, cell retention and differentiation capacity of the CMPCs are low. Combining cells with biomaterials might overcome this problem. By serving as a (temporal) environment, the biomaterial can retain the cells and provide signals that enhance survival, proliferation and differentiation of the cells. To gain more insight into the effect that the encapsulation of CMPCs in a biomaterial has on their behavior, we cultured CMPCs in unidirectional constrained and stress free collagen/Matrigel hydrogels. CMPCs cultured in 3D hydrogels stay viable and keep their cardiomyogenic profile independent of the application of strain. Moreover, the increased expression of Nkx2.5, myocardin and cTnT in 3D hydrogels compared to 2D cultures, suggests enhanced cardiomyogenic differentiation capacity of cells in 3D. Furthermore, increased expression of collagen I, collagen III, elastin and fibronectin and of the matrix remodeling enzymes MMP-1, MMP-2, MMP-9, and TIMP-1 and TIMP-2 in the 3D hydrogels is indicative of an enhanced matrix remodeling capacity of CMPCs in a 3D environment, independent of the application of strain. Interestingly, the additional application of static strain to the 3D hydrogels, as imposed by hydrogel constrainment, stabilized CMPC viability and proliferation, resulted in enhanced cardiac marker protein expression and appeared crucial for cellular organization and morphology. More specifically, CMPCs cultured in 3D collagen/Matrigel constrained hydrogels became readily mechanosensitive, had a rod-shaped morphology, and responded to the applied strain by orienting in the direction of the constraint. Overall, our data demonstrate the applicability of CMPCs in a 3D environment since encapsulation of CMPCs may stabilize survival and proliferation, can enhance the differentiation and remodeling capacity of the cells, and could induce cellular re-organization, which all may contribute to an improved efficiency of cardiac stem cell therapy. PMID- 26278996 TI - A pathological study of the salivary glands of rabid dogs in the Philippines. AB - Rabies is a zoonotic disease caused by the rabies virus. While the salivary glands are important as exit and propagation sites for the rabies virus, the mechanisms of rabies excretion remain unclear. Here, we investigated the histopathology of the salivary glands of rabid dogs and analyzed the mechanism of excretion into the oral cavity. Mandibular and parotid glands of 22 rabid dogs and three control dogs were used. Mild to moderate non-suppurative sialadenitis was observed in the mandibular glands of 19 of the 22 dogs, characterized by loss of acinar epithelium and infiltration by lymphoplasmacytic cells. Viral antigens were detected in the mucous acinar epithelium, ganglion neurons and myoepithelium. Acinar epithelium and lymphocytes were positive for anti-caspase-3 antibodies and TUNEL staining. In contrast, no notable findings were observed in the ductal epithelial cells and serous demilune. In the parotid gland, the acinar cells, myoepithelium and ductal epithelium all tested negative. These findings confirmed the path through which the rabies virus descends along the facial nerve after proliferation in the brain to reach the ganglion neurons of the mandibular gland, subsequently traveling to the acinar epithelium via the salivary gland myoepithelium. Furthermore, the observation that nerve endings passing through the myoepithelium were absent from the ductal system suggested that viral proliferation and cytotoxicity could not occur there, ensuring that secretions containing the virus are efficiently excreted into the oral cavity. PMID- 26278997 TI - Thalamic Dysmetria. PMID- 26278998 TI - CARF (Collaborator of ARF) overexpression in p53-deficient cells promotes carcinogenesis. AB - Collaborator of ARF (CARF), initially identified as a binding partner of ARF (Alternate Reading Frame), has been shown to activate ARF-p53 pathway by multiple ways including stabilization of ARF and p53 tumor suppressor proteins, and transcriptional repression of a p53 antagonist, HDM2. Level of CARF expression was shown to determine fate of cells. Whereas its knockdown caused apoptosis, its over- and super-expressions caused senescence and increase in malignant properties of cancer cells, respectively, and were closely linked to increase and decrease in p53 activity. Using p53-compromised cancer cells, we demonstrate that CARF induces growth arrest when wild type p53 is present and in p53-absence, it promotes carcinogenesis. Biochemical analyses on CARF-induced molecular signaling revealed that in p53-null cells, it caused transcriptional repression of p21(WAF1) leading to increase in CDK4, CDK6, pRb and E2F1 resulting in continued cell cycle progression. Furthermore, it instigated increase in migration and invasion of cancer cells that was marked by upregulation of MMP2, MMP3, MMP9, uPA, several interleukins and VEGF expression. Consistent with these findings, we found that human clinical samples of epithelial and glial cancers (frequently marked by loss of p53 function) possessed high level of CARF expression showing a relationship with cancer aggressiveness. The data demonstrated that CARF could be considered as a diagnostic marker and a therapeutic target in p53-compromised malignancies. PMID- 26278999 TI - A study of MRI changes in Wilson disease and its correlation with clinical features and outcome. AB - OBJECTIVE: To evaluate the sensitivity of different MRI sequences in Wilson disease (WD) with neurological manifestations and its correlation with clinical features and outcome. METHODS: 34 WD patients with neurological manifestation with a median age of 14 years were included. Their Mini Mental State Examination (MMSE) score, movement disorders and laboratory findings were noted. Cranial MRI in T1, T2, FLAIR and DW sequences were done. Outcome at 6 months was categorized into improved (>1 grade improvement), static or worsening. RESULTS: MRI was abnormal in all and revealed involvement of putamen in 29 (85.3%), caudate in 23 (67.6%), brainstem and globus pallidus in 21 (61.8%) each, thalamus in 20 (58.8%), cerebral cortex in 9 (26.5%), subcortical white matter in 8 (23.5%), and cerebellum in 2 (5.9%) patients. The overall sensitivity of T2 and FLAIR was 97.1% each, DWI 38.2% and T1 31.4%. None had contrast enhancement and 4 had reduced ADC value. Choreoathetosis correlated with thalamic, pallidal and putaminal lesions; MMSE with subcortical white mater. MRI load correlated with age, tremor, psychiatric disorder, choreoathetosis, and severity of WD. At 6 months 9 (26.5%) patients improved, 18 (52.9%) remained static and 6 (17.6%) deteriorated. CONCLUSION: In neurologic WD, putaminal involvement is the commonest; T2 and FLAIR sequences have similar sensitivity and number of MRI lesions correlated with disease severity but not with outcome. PMID- 26279001 TI - Revision of the opinion on hydrolysed wheat proteins - Sensitisation only. PMID- 26279002 TI - Antibiotic susceptibility of Neochlamydia hartmanellae and Parachlamydia acanthamoebae in amoebae. AB - Parachlamydia acanthamoebae and Neochlamydia hartmanellae are Chlamydia-related bacteria naturally infecting free-living amoebae. These strict intracellular bacteria might represent emerging pathogens. Recent studies report an association with lower respiratory tract infections, especially with pneumonia where they have been identified as a potential causative agent in 1-2% of cases. In this study, we defined the antibiotic susceptibility of N. hartmanellae, two strains of P. acanthamoebae and two yet unclassified Parachlamydiaceae strains using a quantitative approach. We confirmed the results obtained earlier for P. acanthamoebae strain Bn9 in an observational study. Macrolides (MICs < 0.06-0.5 MUg/ml), rifampicin (MICs 0.25-2) and doxycycline (2-4 MUg/ml) were active against P. acanthamoebae strains and Neochlamydia. All strains were resistant to amoxicillin, ceftriaxone and imipenem (MIC >=32 MUg/ml). Similarly to other Chlamydia-related bacteria, all investigated Parachlamydiaceae were resistant to quinolones (MICs >= 16 MUg/ml). Therefore, we recommend a treatment with macrolides for Parachlamydia-associated pneumonia. PMID- 26279004 TI - Swedish Interactive Threshold Algorithm for central visual field defects unrelated to nerve fiber layer. AB - PURPOSE: To evaluate the characteristic appearance of induced central visual field defects unrelated to the nerve fiber layer on standard automated perimetry using the Swedish Interactive Threshold Algorithm (SITA), and to compare the findings to the appearance on existing Full Threshold (FT) and FASTPAC (FP) algorithms. METHODS: Thirty right eyes of 30 healthy young participants were examined using four Humphrey 24-2 program algorithms: FT, FP, SITA-Standard (SS), and SITA-Fast (SF). Central visual field defects were induced using a high density white opacity filter centered on a plano lens. The test duration, fovea threshold, mean sensitivity (MS), mean deviation (MD), pattern standard deviation (PSD), visual field index (VFI), and defect size and depth were compared among all algorithms. RESULTS: The mean test duration was 21 % to 71 % shorter (p < 0.01), the fovea threshold 0.9 to 2.6 dB higher (p < 0.05), MS 1.1 to 1.7 dB higher (p < 0.05), MD 0.84 to 1.48 dB higher, PSD 0.33 to 0.60 lower, and VFI 2 % higher (p < 0.05) on SS and SF than on FT and FP. The defect size was approximately four points larger and the defect depth 127 to 156 dB shallower on SS and SF than on FT and FP (p < 0.01). CONCLUSIONS: Central visual field defects unrelated to the nerve fiber layer were wider and shallower and global indices were higher on SITA than on conventional FT and FP. These findings indicate that careful attention is required when converting from FT and FP to SITA. PMID- 26279005 TI - The life cycle of Hexangium sigani Goto & Ozaki, 1929 (Digenea: Microscaphidiidae) from the Red Sea. AB - The microscaphidiid Hexangium sigani Goto & Ozaki, 1929 was found in the intestine of Siganus rivulatus, a siganid fish permanently resident in a lagoon within the mangrove swamps on the Egyptian coast of the Gulf of Aqaba. Intra molluscan stages of this trematode (mother sporocysts, rediae and cercariae) were found in the gonads and digestive gland of Nassarius pullus (Gastropoda: Nassariidae), a common snail in the same lagoon. Consequently, the life cycle of H. sigani was elucidated under natural conditions: eggs are directly ingested by the snail; mother sporocysts and rediae reach maturity 5-7 and 16-17 weeks post infection; rediae contain 18-26 developing cercariae; fully developed cercariae are monostome, without penetration glands, emerge from the snail during the night 18-19 weeks post-infection and rapidly encyst on aquatic vegetation (there is no second intermediate host); encysted metacercariae are not progenetic; 2-day-old metacercariae encysted on filamentous algae fed to S. rivulatus developed into fully mature worms 5-6 weeks post-infection. The cycle was completed in about 24 weeks. The intra-molluscan stages are very similar to those of Dictyangium chelydrae Stunkard, 1943, the only described intra-molluscan stages of any microscaphidiid. However, they are also similar to those of the family Mesometridae. The present study of H. sigani describes the first complete microscaphidiid life cycle, and implicitly supports the phylogenetic relationship of this family with the Mesometridae inferred from molecular phylogenetic studies. PMID- 26279003 TI - Elevated vitreous body glial fibrillary acidic protein in retinal diseases. AB - PURPOSE: Increased expression of glial fibrillary acidic protein (GFAP) is a characteristic of gliotic activation (Muller cells and astrocytes) in the retina. This study assessed vitreous body GFAP levels in various forms of retinal pathology. METHODS: This prospective study included 82 patients who underwent vitrectomy (46 retinal detachments (RDs), 13 macular hole (MHs), 15 epiretinal glioses (EGs), 8 organ donors). An established enzyme-linked immunosorbent assay (ELISA, SMI26) was used for quantification of GFAP. RESULTS: The highest concentration of vitreous body GFAP in organ donors was 20 pg/mL and it was used as the cutoff. A significant proportion of patients suffering from RD (65 %) to EG (53 %) had vitreous body GFAP levels above this cutoff when compared to organ donors (0 %, p < 0.0001, p = 0.0194, respectively, Fisher's exact test) and MH (8 %, p < 0.0001, p = 0.0157, respectively). In RD and EG, vitreous body GFAP levels were correlated with axial length (R = 0.69, R = 0.52, p < 0.05 for both). CONCLUSIONS: The data suggest that human vitreous body GFAP is a protein biomarker for glial activation in response to retinal pathologies. Vitreous body GFAP levels may be of interest as a surrogate outcome for experimental treatment strategies in translational studies. PMID- 26279006 TI - Analysis of phospholipids in bio-oils and fats by hydrophilic interaction liquid chromatography-tandem mass spectrometry. AB - A new, sensitive and selective liquid chromatography-electrospray ionization tandem mass spectrometric (LC-ESI-MS/MS) method was developed for the analysis of Phospholipids (PLs) in bio-oils and fats. This analysis employs hydrophilic interaction liquid chromatography-scheduled multiple reaction monitoring (HILIC sMRM) with a ZIC-cHILIC column. Eight PL class selective internal standards (homologs) were used for the semi-quantification of 14 PL classes for the first time. More than 400 scheduled MRMs were used for the measurement of PLs with a run time of 34min. The method's performance was evaluated for vegetable oil, animal fat and algae oil. The averaged within-run precision and between-run precision were <=10% for all of the PL classes that had a direct homologue as an internal standard. The method accuracy was generally within 80-120% for the tested PL analytes in all three sample matrices. PMID- 26279007 TI - Comparison of a stable isotope labeled (SIL) peptide and an extended SIL peptide as internal standards to track digestion variability of an unstable signature peptide during quantification of a cancer biomarker, human osteopontin, from plasma using capillary microflow LC-MS/MS. AB - Human osteopontin (hOPN) is a secreted plasma protein which is elevated in various cancers and is indicative of poor prognosis. Here we describe investigations involving an extended peptide internal standard to track an unstable signature peptide followed by further method development and validation for quantitative measurement of hOPN from plasma using microflow liquid chromatography and tandem mass spectrometry (MFLC-MS/MS). A biologically relevant tryptic peptide 'GDSVVYGLR' was used as a signature peptide for this method. The optimized method involved immunocapture of the analyte protein using hOPN specific antibodies followed by trypsin digestion to obtain the signature peptide. Analysis was carried out on a Waters IonKey/MS system using a flow rate of 2.5MUL/min. Immunocapture buffer was used as a surrogate matrix for the validation studies. The method was validated over a range of 25-600ng/mL. Intra assay and inter-assay accuracies were within +/-13%. Intra-assay and inter-assay precision were within 17%. A stable isotope labeled (SIL) peptide GDSVVYGLR* and an extended SIL peptide TYDGRGDSVV*YGLRSKSKKF were evaluated as internal standards (IS) to account for signature peptide digestion instability and variability. Inherent digestion variability i.e., under controlled conditions, was within +/-20% with both IS peptides. In digestion variability studies, where trypsin activity was varied (20-180%), the use of the extended SIL peptide as an internal standard limited the variability to within +/-30% of the normalized response. Alternatively, when the SIL peptide was used as the internal standard, the variability ranged from -67.4% to 50.6% of the normalized response. The applicability of the validated method was demonstrated by quantification of OPN from plasma samples obtained from 10 healthy individuals and 10 breast cancer patients. The plasma OPN concentrations in healthy individuals ranged from 38 to 85ng/mL with a mean concentration of 55.4+/-15.3ng/mL. A 1.5-12 fold increase in OPN concentrations, ranging from 85 to 637ng/mL, was seen in breast cancer patient samples. PMID- 26279008 TI - Capillary ion chromatography-mass spectrometry for simultaneous determination of glucosylglycerol and sucrose in intracellular extracts of cyanobacteria. AB - A capillary ion chromatography-mass spectrometry (MS) method was proposed to determine glucosylglycerol (GG), sucrose, and five other carbohydrates. MS conditions and make-up flow parameters were optimized. This method is accurate and sensitive for simultaneous analysis of carbohydrates, with mean correlation coefficients of determination greater than 0.99, relative standard deviation of 0.91-2.81% for eight replicates, and average spiked recoveries of 97.3-104.9%. Limits of detection of sodium adduct were obtained with MS detection in selected ion mode for GG (0.006mg/L), sucrose (0.02mg/L), and other carbohydrates (0.03mg/L). This method was successfully applied to determine GG and sucrose in intracellular extracts of salt-stressed cyanobacteria. PMID- 26279009 TI - Development, validation and application of the liquid chromatography tandem mass spectrometry method for simultaneous quantification of azilsartan medoxomil (TAK 491), azilsartan (TAK-536), and its 2 metabolites in human plasma. AB - Azilsartan medoxomil potassium salt (TAK-491) is an orally administered angiotensin II type 1 receptor blocker for the treatment of hypertension and is an ester-based prodrug that is rapidly hydrolyzed to the pharmacologically active moiety, azilsartan (TAK-536), during absorption. TAK-536 is biotransformed to the 2 metabolites M-I by decarboxylation and M-II by dealkylation. In this study, we developed and validated a LC/MS/MS method which can simultaneously determine 4 analytes, TAK-491, TAK-536, M-I and M-II. The bioanalytical method can be outlined as follows: two structural analogues are used as the internal standards. The analytes and the IS are extracted from human plasma using solid phase extraction. After evaporating, the residue is reconstituted and injected into a LC/MS/MS system with an ESI probe and analyzed in the positive ion mode. Separation is performed through a conventional reversed-phase column with a mobile phase of water/acetonitrile/acetic acid (40:60:0.05, v/v/v) mixture at a flow rate of 0.2mL/min. The total run time is 8.5min. The calibration range is 1 2500ng/mL in human plasma for all the analytes. Instability issues of the prodrug, TAK-491, were overcome and all the validation results met the acceptance criteria in accordance with the regulatory guideline/guidance. As a result of the clinical study, the human PK profiles of TAK-536, M-I and M-II were successfully obtained and also it was confirmed that TAK-491 was below the LLOQ (1ng/mL) in the human plasma samples. PMID- 26279010 TI - Development of a stable isotope dilution LC-MS assay for the quantitation of multiple polyethylene glycol (PEG) homologues to be used in permeability studies. AB - A new quantitation method based on a multiple stable isotope dilution assay (SIDA) was developed for polyethylene glycol (PEG) homologues from PEG mixtures with average molecular weights (MW) of 400, 1500, 3000 and 4000Da in urine. Seven [(13)C4(2)H4] and two [(13)C8(2)H8]PEG homologues were synthesized and served as labelled internal standards for SIDA. PEG oligomers were resolved by reversed phase high performance liquid chromatography (RP-HPLC) coupled to mass spectrometry (MS) in multiple ion (MI) scan modus. Very low limits of detection (LODs) in a range of 0.4-12ng/mL were achieved for the single homologues. Higher PEG homologues showed increased LODs and LOQs and less effective recovery (77 87%) than PEG with lower molecular masses (95-121%). Precision (relative standard deviation) varied between 3 and 13% and showed no dependence of the chain length. The method was successfully applied to human and mice urine samples. Beside an accurate quantitation of single PEG homologues it was possible to show an alteration in the MW distribution in urine samples compared to the dosed PEG solutions. The highest MW, with which a PEG can pass the intestinal wall (so called "cut off") for humans appeared to be higher than for mice. PMID- 26279011 TI - Trains, tails and loops of partially adsorbed semi-flexible filaments. AB - Polymer adsorption is a fundamental problem in statistical mechanics that has direct relevance to diverse disciplines ranging from biological lubrication to stability of colloidal suspensions. We combine experiments with computer simulations to investigate depletion induced adsorption of semi-flexible polymers onto a hard-wall. Three dimensional filament configurations of partially adsorbed F-actin polymers are visualized with total internal reflection fluorescence microscopy. This information is used to determine the location of the adsorption/desorption transition and extract the statistics of trains, tails and loops of partially adsorbed filament configurations. In contrast to long flexible filaments which primarily desorb by the formation of loops, the desorption of stiff, finite-sized filaments is largely driven by fluctuating filament tails. Simulations quantitatively reproduce our experimental data and allow us to extract universal laws that explain scaling of the adsorption-desorption transition with relevant microscopic parameters. Our results demonstrate how the adhesion strength, filament stiffness, length, as well as the configurational space accessible to the desorbed filament can be used to design the characteristics of filament adsorption and thus engineer properties of composite biopolymeric materials. PMID- 26279012 TI - 3D liver models on a microplatform: well-defined culture, engineering of liver tissue and liver-on-a-chip. AB - The liver, the largest organ in the human body, is a multi-functional organ with diverse metabolic activities that plays a critical role in maintaining the body and sustaining life. Although the liver has excellent regenerative and recuperative properties, damages caused by chronic liver diseases or viral infection may lead to permanent loss of liver functions. Studies of liver disease mechanism have focused on drug screening and liver tissue engineering techniques, including strategies based on in vitro models. However, conventional liver models are plagued by a number of limitations, which have motivated the development of 'liver-on-a-chip' and microplatform-based bioreactors that can provide well defined microenvironments. Microtechnology is a promising tool for liver tissue engineering and liver system development, as it can mimic the complex in vivo microenvironment and microlevel ultrastructure, by using a small number of human cells under two-dimensional (2D) and three-dimensional (3D) culture conditions. These systems provided by microtechnology allow improved liver-specific functions and can be expanded to encompass diverse 3D culture methods, which are critical for the maintenance of liver functions and recapitulation of the features of the native liver. In this review, we provide an overview of microtechnologies that have been used for liver studies, describe biomimetic technologies for constructing microscale 2D and 3D liver models as well as liver-on-a-chip systems and microscale bioreactors, and introduce applications of liver microtechnology and future trends in the field. PMID- 26279013 TI - Five questions to consider before conducting a stepped wedge trial. AB - Researchers should consider five questions before starting a stepped wedge trial. Why are you planning one? Researchers sometimes think that stepped wedge trials are useful when there is little doubt about the benefit of the intervention being tested. However, if the primary reason for an intervention is to measure its effect, without equipoise there is no ethical justification for delaying implementation in some clusters. By contrast, if you are undertaking pragmatic research, where the primary reason for rolling out the intervention is for it to exert its benefits, and if phased implementation is inevitable, a stepped wedge trial is a valid option and provides better evidence than most non-randomized evaluations. What design will you use? Two common stepped wedge designs are based on the recruitment of a closed or open cohort. In both, individuals may experience both control and intervention conditions and you should be concerned about carry-over effects. In a third, continuous-recruitment, short-exposure design, individuals are recruited as they become eligible and experience either control or intervention condition, but not both. How will you conduct the primary analysis? In stepped wedge trials, control of confounding factors through secular variation is essential. 'Vertical' approaches preserve randomization and compare outcomes between randomized groups within periods. 'Horizontal' approaches compare outcomes before and after crossover to the intervention condition. Most analysis models used in practice combine both types of comparison. The appropriate analytic strategy should be considered on a case-by-case basis. How large will your trial be? Standard sample size calculations for cluster randomized trials do not accommodate the specific features of stepped wedge trials. Methods exist for many stepped wedge designs, but simulation-based calculations provide the greatest flexibility. In some scenarios, such as when the intracluster correlation coefficient is moderate or high, or the cluster size is large, a stepped wedge trial may require fewer clusters than a parallel cluster trial. How will you report your trial? Stepped wedge trials are currently challenging to report using CONSORT principles. Researchers should consider how to demonstrate balance achieved by randomization and how to describe trends for outcomes in both intervention and control clusters. PMID- 26279014 TI - Photocatalytic oxidation of TMB with the double stranded DNA-SYBR Green I complex for label-free and universal colorimetric bioassay. AB - We report here the newly discovered photocatalytic activity of the dsDNA-SYBR Green I (SG) complex, which can catalyze the oxidation of 3,3',5,5' tetramethylbenzidine (TMB) under light irradiation corresponding to the excitation of the dsDNA-SG complex. The most appealing feature of the photocatalytic system here is that it can be obtained using random DNA sequences that can form a duplex. Considering the universality of the photooxidase, a label free and universal platform was proposed for highly sensitive visual bioassays. PMID- 26279015 TI - Breast Radiation Therapy--Sometimes Less May Be More. PMID- 26279016 TI - The Red Journal's Top Downloads of 2014. PMID- 26279017 TI - Thoracic Radiation Therapy in Extensive Disease Small Cell Lung Cancer. PMID- 26279018 TI - Extensive-Stage Small Cell Lung Cancer: Is Consolidative Thoracic Radiation Therapy Really a New Standard of Care? PMID- 26279019 TI - "Feeding the Beast" Is Not the Road to Value. PMID- 26279020 TI - Prospective Longitudinal Assessment of Quality of Life for Liver Cancer Patients Treated With Stereotactic Body Radiation Therapy. AB - PURPOSE: To evaluate quality of life (QoL), an important outcome owing to poor long-term survival, after stereotactic body radiation therapy (SBRT) to the liver. METHODS AND MATERIALS: Patients (n=222) with hepatocellular carcinoma (HCC), liver metastases, or intrahepatic cholangiocarcinoma and Child-Pugh A liver function received 24-60 Gy of 6-fraction image-guided SBRT. Prospective QoL assessment was completed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) and/or Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep, version 4) questionnaires at baseline and 1, 3, 6, and 12 months after treatment. Ten HCC patients with Child-Pugh B liver function were also treated. RESULTS: The QLQ-C30 was available for 205 patients, and 196 completed the FACT-Hep. No difference in baseline QoL (P = .17) or overall survival (P = .088) was seen between the HCC, liver metastases, and intrahepatic cholangiocarcinoma patients. Appetite loss and fatigue measured by the QLQ-C30 clinically and statistically worsened by 1 month after treatment but recovered by 3 months. At 3 and 12 months after treatment, respectively, the FACT-Hep score had improved relative to baseline in 13%/19%, worsened in 36%/27%, and remained stable in 51%/54%. Using the QLQ-C30 Global Health score, QoL improved in 16%/23%, worsened in 34%/39%, and remained stable in 50%/38% at 3 and 12 months, respectively. Median survival was 17.0 months (95% confidence interval [CI] 12.3-19.8 months). Higher baseline scores on both FACT Hep and QLQ-C30 Global Health were associated with improved survival. Hazard ratios for death, per 10-unit decrease in QoL, were 0.90 (95% CI 0.83-0.98; P = .001) and 0.88 (95% CI 0.82-0.95; P = .001), respectively. Tumor size was inversely correlated with survival. CONCLUSIONS: Liver SBRT temporarily worsens appetite and fatigue, but not overall QoL. Stereotactic body radiation therapy is well tolerated and warrants comparison against other liver-directed therapies. PMID- 26279021 TI - Stereotactic Body Radiation Therapy for Liver Cancer: Effective Therapy With Minimal Impact on Quality of Life. PMID- 26279022 TI - COSMIC: A Regimen of Intensity Modulated Radiation Therapy Plus Dose-Escalated, Raster-Scanned Carbon Ion Boost for Malignant Salivary Gland Tumors: Results of the Prospective Phase 2 Trial. AB - PURPOSE: To investigate the effect of intensity modulated radiation therapy (IMRT) and dose-escalated carbon ion (C12) therapy in adenoid cystic carcinoma (ACC) and other malignant salivary gland tumors (MSGTs) of the head and neck. PATIENTS AND METHODS: COSMIC (combined treatment of malignant salivary gland tumors with intensity modulated radiation therapy and carbon ions) is a prospective phase 2 trial of 24 Gy(RBE) C12 followed by 50 Gy IMRT in patients with pathologically confirmed MSGT. The primary endpoint is mucositis Common Terminology Criteria grade 3; the secondary endpoints are locoregional control (LC), progression-free survival (PFS), overall survival (OS), and toxicity. Toxicity was scored according to the Common Terminology Criteria for Adverse Events version 3; treatment response was scored according to Response Evaluation Criteria in Solid Tumors 1.1. RESULTS: Between July 2010 and August 2011, 54 patients were accrued, and 53 were available for evaluation. The median follow-up time was 42 months; patients with microscopically incomplete resections (R1, n = 20), gross residual disease (R2, n = 17), and inoperable disease (n = 16) were included. Eighty-nine percent of patients had ACC, and 57% had T4 tumors. The most common primary sites were paranasal sinus (34%), submandibular gland, and palate. At the completion of radiation therapy, 26% of patients experienced grade 3 mucositis, and 20 patients reported adverse events of the ear (38%). The most common observed late effects were grade 1 xerostomia (49%), hearing impairment (25%, 2% ipsilateral hearing loss), and adverse events of the eye (20%), but no visual impairment or loss of vision. Grade 1 central nervous system necrosis occurred in 6%, and 1 grade 4 ICA hemorrhage without neurologic sequelae. The best response was 54% (complete response/partial remission). At 3 years, the LC, PFS, and OS were 81.9%, 57.9%, and 78.4%, respectively. No difference was found regarding resection status. The most common site of failure was distant (55%). Local relapse was predominantly in field (79%). CONCLUSION: Treatment was tolerated, with moderate acute and late toxicity. The LC at 3 years was promising. No significant difference could be shown regarding resection status; hence, extensive and mutilating surgical procedures should be rediscussed. Further dose escalation may be limited in view of potential vascular adverse events. PMID- 26279023 TI - Pulmonary Function After Treatment for Embryonal Brain Tumors on SJMB03 That Included Craniospinal Irradiation. AB - PURPOSE: The treatment of children with embryonal brain tumors (EBT) includes craniospinal irradiation (CSI). There are limited data regarding the effect of CSI on pulmonary function. METHODS: Protocol SJMB03 enrolled patients 3 to 21 years of age with EBT. Pulmonary function tests (PFTs) (forced expiratory volume in 1 second [FEV1] and forced vital capacity [FVC] by spirometry, total lung capacity [TLC] by nitrogen washout or plethysmography, and diffusing capacity of the lung for carbon monoxide corrected for hemoglobin [DLCO(corr)]) were obtained. Differences between PFTs obtained immediately after the completion of CSI and 24 or 60 months after the completion of treatment (ACT) were compared using exact Wilcoxon signed-rank tests and repeated-measures models. RESULTS: Between June 24, 2003, and March 1, 2010, 303 eligible patients (spine dose: <= 2345 cGy, 201; >2345 cGy, 102; proton beam, 20) were enrolled, 260 of whom had at least 1 PFT. The median age at diagnosis was 8.9 years (range, 3.1-20.4 years). The median thoracic spinal radiation dose was 23.4 Gy (interquartile range [IQR], 23.4-36.0 Gy). The median cyclophosphamide dose was 16.0 g/m(2) (IQR, 15.7-16.0 g/m(2)). At 24 and 60 months ACT, DLCO(corr) was <75% predicted in 23% (27/118) and 25% (21/84) of patients, FEV1 was <80% predicted in 20% (34/170) and 29% (32/109) of patients, FVC was <80% predicted in 27% (46/172) and 28% (30/108) of patients, and TLC was <75% predicted in 9% (13/138) and 11% (10/92) of patients. DLCO(corr) was significantly decreased 24 months ACT (median difference [MD] in % predicted, 3.00%; P = .028) and 60 months ACT (MD in % predicted, 6.00%; P = .033) compared with the end of radiation therapy. These significant decreases in DLCO(corr) were also observed in repeated-measures models (P = .011 and P = .032 at 24 and 60 months ACT, respectively). CONCLUSIONS: A significant minority of EBT survivors experience PFT deficits after CSI. Continued monitoring of this cohort is planned. PMID- 26279024 TI - Imaging Changes in Pediatric Intracranial Ependymoma Patients Treated With Proton Beam Radiation Therapy Compared to Intensity Modulated Radiation Therapy. AB - PURPOSE: The clinical significance of magnetic resonance imaging (MRI) changes after radiation therapy (RT) in children with ependymoma is not well defined. We compared imaging changes following proton beam radiation therapy (PBRT) to those after photon-based intensity modulated RT (IMRT). METHODS AND MATERIALS: Seventy two patients with nonmetastatic intracranial ependymoma who received postoperative RT (37 PBRT, 35 IMRT) were analyzed retrospectively. MRI images were reviewed by 2 neuroradiologists. RESULTS: Sixteen PBRT patients (43%) developed postradiation MRI changes at 3.8 months (median) with resolution by 6.1 months. Six IMRT patients (17%) developed changes at 5.3 months (median) with 8.3 months to resolution. Mean age at radiation was 4.4 and 6.9 years for PBRT and IMRT, respectively (P = .06). Age at diagnosis (>3 years) and time of radiation (>=3 years) was associated with fewer imaging changes on univariate analysis (odds ratio [OR]: 0.35, P = .048; OR: 0.36, P = .05). PBRT (compared to IMRT) was associated with more frequent imaging changes, both on univariate (OR: 3.68, P = .019) and multivariate (OR: 3.89, P = .024) analyses. Seven (3 IMRT, 4 PBRT) of 22 patients with changes had symptoms requiring intervention. Most patients were treated with steroids; some PBRT patients also received bevacizumab and hyperbaric oxygen therapy. None of the IMRT patients had lasting deficits, but 2 patients died from recurrent disease. Three PBRT patients had persistent neurological deficits, and 1 child died secondarily to complications from radiation necrosis. CONCLUSIONS: Postradiation MRI changes are more common with PBRT and in patients less than 3 years of age at diagnosis and treatment. It is difficult to predict causes for development of imaging changes that progress to clinical significance. These changes are usually self-limiting, but some require medical intervention, especially those involving the brainstem. PMID- 26279025 TI - Effects of Surgery and Proton Therapy on Cerebral White Matter of Craniopharyngioma Patients. AB - PURPOSE: The purpose of this study was to determine radiation dose effect on the structural integrity of cerebral white matter in craniopharyngioma patients receiving surgery and proton therapy. METHODS AND MATERIALS: Fifty-one patients (2.1-19.3 years of age) with craniopharyngioma underwent surgery and proton therapy in a prospective therapeutic trial. Anatomical magnetic resonance images acquired after surgery but before proton therapy were inspected to identify white matter structures intersected by surgical corridors and catheter tracks. Longitudinal diffusion tensor imaging (DTI) was performed to measure microstructural integrity changes in cerebral white matter. Fractional anisotropy (FA) derived from DTI was statistically analyzed for 51 atlas-based white matter structures of the brain to determine radiation dose effect. FA in surgery affected regions in the corpus callosum was compared to that in its intact counterpart to determine whether surgical defects affect radiation dose effect. RESULTS: Surgical defects were seen most frequently in the corpus callosum because of transcallosal resection of tumors and insertion of ventricular or cyst catheters. Longitudinal DTI data indicated reductions in FA 3 months after therapy, which was followed by a recovery in most white matter structures. A greater FA reduction was correlated with a higher radiation dose in 20 white matter structures, indicating a radiation dose effect. The average FA in the surgery-affected regions before proton therapy was smaller (P=.0001) than that in their non-surgery-affected counterparts with more intensified subsequent reduction of FA (P=.0083) after therapy, suggesting that surgery accentuated the radiation dose effect. CONCLUSIONS: DTI data suggest that mild radiation dose effects occur in patients with craniopharyngioma receiving surgery and proton therapy. Surgical defects present at the time of proton therapy appear to accentuate the radiation dose effect longitudinally. This study supports consideration of pre-existing surgical defects and their locations in proton therapy planning and studies of treatment effect. PMID- 26279026 TI - Precision Hypofractionated Radiation Therapy in Poor Performing Patients With Non Small Cell Lung Cancer: Phase 1 Dose Escalation Trial. AB - PURPOSE: Treatment regimens for locally advanced non-small cell lung cancer (NSCLC) give suboptimal clinical outcomes. Technological advancements such as radiation therapy, the backbone of most treatment regimens, may enable more potent and effective therapies. The objective of this study was to escalate radiation therapy to a tumoricidal hypofractionated dose without exceeding the maximally tolerated dose (MTD) in patients with locally advanced NSCLC. METHODS AND MATERIALS: Patients with stage II to IV or recurrent NSCLC and Eastern Cooperative Oncology Group performance status of 2 or greater and not candidates for surgical resection, stereotactic radiation, or concurrent chemoradiation were eligible. Highly conformal radiation therapy was given to treat intrathoracic disease in 15 fractions to a total of 50, 55, or 60 Gy. RESULTS: Fifty-five patients were enrolled: 15 at the 50-Gy, 21 at the 55-Gy, and 19 at the 60-Gy dose levels. A 90-day follow-up was completed in each group without exceeding the MTD. With a median follow-up of 12.5 months, there were 93 grade >= 3 adverse events (AEs), including 39 deaths, although most AEs were considered related to factors other than radiation therapy. One patient from the 55- and 60-Gy dose groups developed grade >= 3 esophagitis, and 5, 4, and 4 patients in the respective dose groups experienced grade >= 3 dyspnea, but only 2 of these AEs were considered likely related to therapy. There was no association between fraction size and toxicity (P = .24). The median overall survival was 6 months with no significant differences between dose levels (P = .59). CONCLUSIONS: Precision hypofractionated radiation therapy consisting of 60 Gy in 15 fractions for locally advanced NSCLC is generally well tolerated. This treatment regimen could provide patients with poor performance status a potent alternative to chemoradiation. This study has implications for the cost effectiveness of lung cancer therapy. Additional studies of long-term safety and efficacy of this therapy are warranted. PMID- 26279027 TI - Utilization and Outcomes of Breast Brachytherapy in Younger Women. AB - PURPOSE: To directly compare (1) radiation treatment utilization patterns; (2) risks of subsequent mastectomy; and (3) costs of radiation treatment in patients treated with brachytherapy versus whole-breast irradiation (WBI), in a national, contemporary cohort of women with incident breast cancer, aged 64 years and younger. METHODS AND MATERIALS: Using MarketScan health care claims data, we identified 45,884 invasive breast cancer patients (aged 18-64 years), treated from 2003 to 2010 with lumpectomy, followed by brachytherapy (n = 3134) or whole breast irradiation (n = 42,750). We stratified patients into risk groups according to age (Age < 50 vs Age >= 50) and endocrine therapy status (Endocrine- vs Endocrine+). "Endocrine+" patients filled an endocrine therapy prescription within 1 year after lumpectomy. Pathologic hormone receptor status was not available in this dataset. In brachytherapy versus WBI patients, utilization trends and 5-year subsequent mastectomy risks were compared. Stratified, adjusted subsequent mastectomy risks were calculated using proportional hazards regression. RESULTS: Brachytherapy utilization increased from 2003 to 2010: in patients Age < 50, from 0.6% to 4.9%; patients Age >= 50 from 2.2% to 11.3%; Endocrine- patients, 1.3% to 9.4%; Endocrine+ patients, 1.9% to 9.7%. Age influenced treatment selection more than endocrine status: 17% of brachytherapy patients were Age < 50 versus 32% of WBI patients (P < .001); whereas 41% of brachytherapy patients were Endocrine-versus 44% of WBI patients (P = .003). Highest absolute 5-year subsequent mastectomy risks occurred in Endocrine-/Age < 50 patients (24.4% after brachytherapy vs 9.0% after WBI (hazard ratio [HR] 2.18, 95% confidence interval [CI] 1.37-3.47); intermediate risks in Endocrine-/Age >= 50 patients (8.6% vs 4.9%; HR 1.76, 95% CI 1.26-2.46); and lowest risks in Endocrine+ patients of any age: Endocrine+/Age < 50 (5.5% vs 4.5%; HR 1.18, 95% CI 0.61-2.31); Endocrine+/Age >= 50 (4.2% vs 2.4%; HR 1.71, 95% CI 1.16-2.51). CONCLUSION: In this younger cohort, endocrine status was a valuable discriminatory factor predicting subsequent mastectomy risk after brachytherapy versus WBI and therefore may be useful for selecting appropriate younger brachytherapy candidates. PMID- 26279028 TI - Role of Ultrasonography of Regional Nodal Basins in Staging Triple-Negative Breast Cancer and Implications For Local-Regional Treatment. AB - PURPOSE: We sought to determine the rate at which regional nodal ultrasonography would increase the nodal disease stage in patients with triple-negative breast cancer (TNBC) beyond the clinical stage determined by physical examination and mammography alone, and significantly affect the treatments delivered to these patients. METHODS AND MATERIALS: We retrospectively reviewed the charts of women with stages I to III TNBC who underwent physical examination, mammography, breast and regional nodal ultrasonography with needle biopsy of abnormal nodes, and definitive local-regional treatment at our institution between 2004 and 2011. The stages of these patients' disease with and without ultrasonography of the regional nodal basins were compared using the Pearson chi(2) test. Definitive treatments of patients whose nodal disease was upstaged on the basis of ultrasonographic findings were compared to those of patients whose disease stage remained the same. RESULTS: A total of 572 women met the study requirements. In 111 (19.4%) of these patients, regional nodal ultrasonography with needle biopsy resulted in an increase in disease stage from the original stage by physical examination and mammography alone. Significantly higher percentages of patients whose nodal disease was upstaged by ultrasonographic findings compared to that in patients whose disease was not upstaged underwent neoadjuvant systemic therapy (91.9% and 51.2%, respectively; P<.0001), axillary lymph node dissection (99.1% and 34.5%, respectively; P<.0001), and radiation to the regional nodal basins (88.2% and 29.1%, respectively; P<.0001). CONCLUSIONS: Regional nodal ultrasonography in TNBC frequently changes the initial clinical stage and plays an important role in treatment planning. PMID- 26279030 TI - Interval From Imaging to Treatment Delivery in the Radiation Surgery Age: How Long Is Too Long? AB - PURPOSE: The purpose of this study was to evaluate workflow and patient outcomes related to frameless stereotactic radiation surgery (SRS) for brain metastases. METHODS AND MATERIALS: We reviewed all treatment demographics, clinical outcomes, and workflow timing, including time from magnetic resonance imaging (MRI), computed tomography (CT) simulation, insurance authorization, and consultation to the start of SRS for brain metastases. RESULTS: A total of 82 patients with 151 brain metastases treated with SRS were evaluated. The median times from consultation, insurance authorization, CT simulation, and MRI for treatment planning were 15, 7, 6, and 11 days to SRS. Local freedom from progression (LFFP) was lower in metastases with MRI >= 14 days before treatment (P = .0003, log rank). The 6- and 12-month LFFP rate were 95% and 75% for metastasis with interval of <14 days from MRI to treatment compared to 56% and 34% for metastases with MRI >= 14 days before treatment. On multivariate analysis, LFFP remained significantly lower for lesions with MRI >= 14 days at SRS (P = .002, Cox proportional hazards; hazard ratio: 3.4, 95% confidence interval: 1.6-7.3). CONCLUSIONS: Delay from MRI to SRS treatment delivery for brain metastases appears to reduce local control. Future studies should monitor the timing from imaging acquisition to treatment delivery. Our experience suggests that the time from MRI to treatment should be <14 days. PMID- 26279029 TI - Impact of Pretreatment Combined (18)F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Staging on Radiation Therapy Treatment Decisions in Locally Advanced Breast Cancer. AB - PURPOSE: To assess the diagnostic performance of pretreatment (18)F fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) and its impact on radiation therapy treatment decisions in patients with locally advanced breast cancer (LABC). METHODS AND MATERIALS: Patients with LABC with Eastern Cooperative Oncology Group performance status <2 and no contraindication to neoadjuvant chemotherapy, surgery, and adjuvant radiation therapy were enrolled on a prospective trial. All patients had pretreatment conventional imaging (CI) performed, including bilateral breast mammography and ultrasound, bone scan, and CT chest, abdomen, and pelvis scans performed. Informed consent was obtained before enrolment. Pretreatment whole-body (18)F-FDG PET/CT scans were performed on all patients, and results were compared with CI findings. RESULTS: A total of 154 patients with LABC with no clinical or radiologic evidence of distant metastases on CI were enrolled. Median age was 49 years (range, 26-70 years). Imaging with PET/CT detected distant metastatic disease and/or locoregional disease not visualized on CI in 32 patients (20.8%). Distant metastatic disease was detected in 17 patients (11.0%): 6 had bony metastases, 5 had intrathoracic metastases (pulmonary/mediastinal), 2 had distant nodal metastases, 2 had liver metastases, 1 had pulmonary and bony metastases, and 1 had mediastinal and distant nodal metastases. Of the remaining 139 patients, nodal disease outside conventional radiation therapy fields was detected on PET/CT in 15 patients (10.8%), with involvement of ipsilateral internal mammary nodes in 13 and ipsilateral level 5 cervical nodes in 2. CONCLUSIONS: Imaging with PET/CT provides superior diagnostic and staging information in patients with LABC compared with CI, which has significant therapeutic implications with respect to radiation therapy management. Imaging with PET/CT should be considered in all patients undergoing primary staging for LABC. PMID- 26279031 TI - Urinary and Rectal Toxicity Profiles After Permanent Iodine-125 Implant Brachytherapy in Japanese Men: Nationwide J-POPS Multi-institutional Prospective Cohort Study. AB - PURPOSE: To assess, in a nationwide multi-institutional cohort study begun in 2005 and in which 6927 subjects were enrolled by 2010, the urinary and rectal toxicity profiles of subjects who enrolled during the first 2 years, and evaluate the toxicity profiles for permanent seed implantation (PI) and a combination therapy with PI and external beam radiation therapy (EBRT). METHODS AND MATERIALS: Baseline data for 2339 subjects out of 2354 patients were available for the analyses. Toxicities were evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events, and the International Prostate Symptom Scores were recorded prospectively until 36 months after radiation therapy. RESULTS: Grade 2+ acute urinary toxicities developed in 7.36% (172 of 2337) and grade 2+ acute rectal toxicities developed in 1.03% (24 of 2336) of the patients. Grade 2+ late urinary and rectal toxicities developed in 5.75% (133 of 2312) and 1.86% (43 of 2312) of the patients, respectively. A higher incidence of grade 2+ acute urinary toxicity occurred in the PI group than in the EBRT group (8.49% vs 3.66%; P<.01). Acute rectal toxicity outcomes were similar between the treatment groups. The 3-year cumulative incidence rates for grade 2+ late urinary toxicities were 6.04% versus 4.82% for the PI and the EBRT groups, respectively, with no significant differences between the treatment groups. The 3-year cumulative incidence rates for grade 2+ late rectal toxicities were 0.90% versus 5.01% (P<.01) for the PI and the EBRT groups, respectively. The mean of the postimplant International Prostate Symptom Score peaked at 3 months, but it decreased to a range that was within 2 points of the baseline score, which was observed in 1625 subjects (69.47%) at the 1-year follow-up assessment. CONCLUSIONS: The acute urinary toxicities observed were acceptable given the frequency and retention, and the late rectal toxicities were more favorable than those of other studies. PMID- 26279033 TI - Carbon-Ion Irradiation Suppresses Migration and Invasiveness of Human Pancreatic Carcinoma Cells MIAPaCa-2 via Rac1 and RhoA Degradation. AB - PURPOSE: To investigate the mechanisms underlying the inhibition of cancer cell migration and invasion by carbon (C)-ion irradiation. METHODS AND MATERIALS: Human pancreatic cancer cells MIAPaCa-2, AsPC-1, and BxPC-3 were treated by x-ray (4 Gy) or C-ion (0.5, 1, 2, or 4 Gy) irradiation, and their migration and invasion were assessed 2 days later. The levels of guanosine triphosphate (GTP) bound Rac1 and RhoA were determined by the active GTPase pull-down assay with or without a proteasome inhibitor, and the binding of E3 ubiquitin ligase to GTP bound Rac1 was examined by immunoprecipitation. RESULTS: Carbon-ion irradiation reduced the levels of GTP-bound Rac1 and RhoA, 2 major regulators of cell motility, in MIAPaCa-2 cells and GTP-bound Rac1 in AsPC-1 and BxPC-3 cells. Proteasome inhibition reversed the effect, indicating that C-ion irradiation induced Rac1 and RhoA degradation via the ubiquitin (Ub)-proteasome pathway. E3 Ub ligase X-linked inhibitor of apoptosis protein (XIAP), which directly targets Rac1, was selectively induced in C-ion--irradiated MIAPaCa-2 cells and coprecipitated with GTP-bound Rac1 in C-ion--irradiated cells, which was associated with Rac1 ubiquitination. Cell migration and invasion reduced by C-ion radiation were restored by short interfering RNA--mediated XIAP knockdown, indicating that XIAP is involved in C-ion--induced inhibition of cell motility. CONCLUSION: In contrast to x-ray irradiation, C-ion treatment inhibited the activity of Rac1 and RhoA in MIAPaCa-2 cells and Rac1 in AsPC-1 and BxPC-3 cells via Ub-mediated proteasomal degradation, thereby blocking the motility of these pancreatic cancer cells. PMID- 26279032 TI - Indirect Tumor Cell Death After High-Dose Hypofractionated Irradiation: Implications for Stereotactic Body Radiation Therapy and Stereotactic Radiation Surgery. AB - PURPOSE: The purpose of this study was to reveal the biological mechanisms underlying stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS). METHODS AND MATERIALS: FSaII fibrosarcomas grown subcutaneously in the hind limbs of C3H mice were irradiated with 10 to 30 Gy of X rays in a single fraction, and the clonogenic cell survival was determined with in vivo--in vitro excision assay immediately or 2 to 5 days after irradiation. The effects of radiation on the intratumor microenvironment were studied using immunohistochemical methods. RESULTS: After cells were irradiated with 15 or 20 Gy, cell survival in FSaII tumors declined for 2 to 3 days and began to recover thereafter in some but not all tumors. After irradiation with 30 Gy, cell survival declined continuously for 5 days. Cell survival in some tumors 5 days after 20 to 30 Gy irradiation was 2 to 3 logs less than that immediately after irradiation. Irradiation with 20 Gy markedly reduced blood perfusion, upregulated HIF-1alpha, and increased carbonic anhydrase-9 expression, indicating that irradiation increased tumor hypoxia. In addition, expression of VEGF also increased in the tumor tissue after 20 Gy irradiation, probably due to the increase in HIF-1alpha activity. CONCLUSIONS: Irradiation of FSaII tumors with 15 to 30 Gy in a single dose caused dose-dependent secondary cell death, most likely by causing vascular damage accompanied by deterioration of intratumor microenvironment. Such indirect tumor cell death may play a crucial role in the control of human tumors with SBRT and SRS. PMID- 26279034 TI - Accuracy and Utility of Deformable Image Registration in (68)Ga 4D PET/CT Assessment of Pulmonary Perfusion Changes During and After Lung Radiation Therapy. AB - PURPOSE: Measuring changes in lung perfusion resulting from radiation therapy dose requires registration of the functional imaging to the radiation therapy treatment planning scan. This study investigates registration accuracy and utility for positron emission tomography (PET)/computed tomography (CT) perfusion imaging in radiation therapy for non-small cell lung cancer. METHODS: (68)Ga 4 dimensional PET/CT ventilation-perfusion imaging was performed before, during, and after radiation therapy for 5 patients. Rigid registration and deformable image registration (DIR) using B-splines and Demons algorithms was performed with the CT data to obtain a deformation map between the functional images and planning CT. Contour propagation accuracy and correspondence of anatomic features were used to assess registration accuracy. Wilcoxon signed-rank test was used to determine statistical significance. Changes in lung perfusion resulting from radiation therapy dose were calculated for each registration method for each patient and averaged over all patients. RESULTS: With B-splines/Demons DIR, median distance to agreement between lung contours reduced modestly by 0.9/1.1 mm, 1.3/1.6 mm, and 1.3/1.6 mm for pretreatment, midtreatment, and posttreatment (P < .01 for all), and median Dice score between lung contours improved by 0.04/0.04, 0.05/0.05, and 0.05/0.05 for pretreatment, midtreatment, and posttreatment (P < .001 for all). Distance between anatomic features reduced with DIR by median 2.5 mm and 2.8 for pretreatment and midtreatment time points, respectively (P = .001) and 1.4 mm for posttreatment (P > .2). Poorer posttreatment results were likely caused by posttreatment pneumonitis and tumor regression. Up to 80% standardized uptake value loss in perfusion scans was observed. There was limited change in the loss in lung perfusion between registration methods; however, Demons resulted in larger interpatient variation compared with rigid and B-splines registration. CONCLUSIONS: DIR accuracy in the data sets studied was variable depending on anatomic changes resulting from radiation therapy; caution must be exercised when using DIR in regions of low contrast or radiation pneumonitis. Lung perfusion reduces with increasing radiation therapy dose; however, DIR did not translate into significant changes in dose-response assessment. PMID- 26279035 TI - Treatment Modalities Should Be Based Upon Efficacy and Cost: Early Stage NSCLC, a Case in Point. PMID- 26279036 TI - Treatment Costs of Early-Stage Lung Cancers Detected by Low-Dose Computed Tomography Screening. PMID- 26279037 TI - Maintenance of Certification: From Realism to Skepticism. PMID- 26279038 TI - In Reply to Wang et al. PMID- 26279039 TI - Personalized imaging in radiation oncology: In Regard to Zhang et al. PMID- 26279040 TI - In Reply to Govardhan et al. PMID- 26279041 TI - Chemoradiation followed by surgery for advanced cervical cancer: In Regard to Ferrandina et al. PMID- 26279042 TI - Regional lymph node radiation and lymphedema. In Regard to Chandra et al. PMID- 26279043 TI - In Reply to Lawrence. PMID- 26279044 TI - Charged particle with helium ion versus iodine-125 plaque therapy: In Regard to Mishra et al. PMID- 26279045 TI - In Reply to Kamrava and McCannel. PMID- 26279046 TI - Radiation as a foundation for glioblastoma therapy in elderly patients. In Regard to Arvold et al. PMID- 26279047 TI - In Reply to Levra et al. PMID- 26279048 TI - Stereotactic radiosurgery with or without WBRT for brain metastases: In Regard to Sahgal et al. PMID- 26279049 TI - In Regard to Sahgal et al. PMID- 26279050 TI - Appendicular lean mass and site-specific muscle loss in the extremities correlate with dynamic strength. AB - BACKGROUND: Previous studies have reported the non-homogenous loss of muscle mass (site-specific muscle loss) with ageing, but this relationship to the loss of strength is not totally understood. PURPOSE: To investigate the relationship between maximal dynamic strength and site-specific muscle mass of the thigh and upper arm. METHODS: Thirty-five recreationally active men were separated into young-aged (YG, 20-39 years, n = 12), middle-aged (MG, 40-59 years, n = 13) and old-aged groups (OG, 60-75 years, n = 10). One-repetition maximum strength (1-RM; leg press, chest press, knee flexion, lat pull-down, and knee extension), muscle thickness (MTH, anterior and posterior thigh and upper arm) and appendicular lean mass (aLM) index were obtained from participants. Site-specific thigh MTH ratio was determined by dividing anterior thigh MTH (50% of thigh length) by posterior thigh MTH (50% of thigh length). RESULTS: aLM index was not significantly different between age groups, but a significantly smaller site-specific MTH thigh ratio was found in the OG. Collapsed across age groups both site-specific thigh MTH ratio and aLM index were significantly correlated with leg press, knee extension and knee flexion1-RM strength (r = 0.390-0.699), but not with knee extension: knee flexion (KE:KF) 1-RM strength ratios (r = 0.037-0.081). Separated by age groups only aLM index was correlated with KE:KF 1-RM ratio for the OG (r = 0.780). CONCLUSIONS: Site-specific thigh MTH ratio may be an important assessment tool in older individuals as it is different among age groups and is significantly related to dynamic maximal strength. However, maximal dynamic strength ratios appear to be less sensitive to differences in site-specific MTH ratios. PMID- 26279051 TI - Novel Prokinetic Acotiamide Reduces Transient Lower Esophageal Sphincter Relaxation in Healthy Subjects. AB - BACKGROUND/AIMS: Currently, there is no study evaluating the effect of acotiamide on transient lower esophageal sphincter relaxations (TLESRs). The aim of this study was to evaluate the effect of acotiamide on TLESRs using simultaneous high resolution manometry (HRM) and impedance-pH monitoring. METHODS: Ten healthy subjects were enrolled. On day 1, subjects underwent HRM and impedance-pH recordings as a baseline. Subjects ate a 750-kcal liquid meal; recording was continued for 2 h while the subjects were in a sitting position. After the administration of acotiamide 100 mg three times a day for 1 week, subjects underwent HRM and impedance-pH recording under the same protocol. RESULTS: A total of 208 TLESRs were identified at baseline. Acotiamide decreased the total number of TLESRs from 208 to 143 (p < 0.05). The rate of reflux events during TLESRs after acotiamide administration was similar to that at baseline (57% after acotiamide vs. 58% at baseline). Bolus clearance time was significantly reduced by acotiamide. CONCLUSIONS: Acotiamide was believed to have the potential for reducing TLESRs and for enhancing esophageal bolus clearance in healthy volunteers. Future research is needed to determine whether the effects of acotiamide that reduce TLESRs and enhance esophageal motility could improve symptoms in patients with refractory gastroesophageal reflux disease. PMID- 26279053 TI - Combination of European System for Cardiac Operative Risk Evaluation (EuroSCORE) and Cardiac Surgery Score (CASUS) to Improve Outcome Prediction in Cardiac Surgery. AB - BACKGROUND We hypothesized that the combination of a preoperative and a postoperative scoring system would improve the accuracy of mortality prediction and therefore combined the preoperative 'additive EuroSCORE' (European system for cardiac operative risk evaluation) with the postoperative 'additive CASUS' (Cardiac Surgery Score) to form the 'modified CASUS'. MATERIAL AND METHODS We included all consecutive adult patients after cardiac surgery during January 2007 and December 2010 in our prospective study. Our single-centre study was conducted in a German general referral university hospital. The original additive and the 'modified CASUS' were tested using calibration and discrimination statistics. We compared the area under the curve (AUC) of the receiver characteristic curves (ROC) by DeLong's method and calculated overall correct classification (OCC) values. RESULTS The mean age among the total of 5207 patients was 67.2 +/- 10.9 years. Whilst the ICU mortality was 5.9% we observed a mean length of ICU stay of 4.6 +/- 7.0 days. Both models demonstrated excellent discriminatory power (mean AUC of 'modified CASUS': >= 0.929; 'additive CASUS': >= 0.920), with no significant differences according to DeLong. Neither model showed a significant p value (<0.05) in calibration. We detected the best OCC during the 2nd day (modified: 96.5%; original: 96.6%). CONCLUSIONS Our 'additive' and 'modified' CASUS are reasonable overall predictors. We could not detect any improvement in the accuracy of mortality prediction in cardiac surgery by combining a preoperative and a postoperative scoring system. A separate calculation of the two individual elements is therefore recommended. PMID- 26279054 TI - Self-Assembled Multimetallic/Peptide Complexes: Structures and Unimolecular Reactions of [Mn (GlyGly-H)2n-1 ](+) and Mn+1 (GlyGly-H2n ](2+) Clusters in the Gas Phase. AB - The unimolecular chemistry and structures of self-assembled complexes containing multiple alkaline-earth-metal dications and deprotonated GlyGly ligands are investigated. Singly and doubly charged ions [Mn (GlyGly-H)n-1 ](+) (n=2-4), [Mn+1 (GlyGly-H)2n ](2+) (n=2,4,6), and [M(GlyGly-H)GlyGly](+) were observed. The losses of 132 Da (GlyGly) and 57 Da (determined to be aminoketene) were the major dissociation pathways for singly charged ions. Doubly charged Mg(2+) clusters mainly lost GlyGly, whereas those containing Ca(2+) or Sr(2+) also underwent charge separation. Except for charge separation, no loss of metal cations was observed. Infrared multiple photon dissociation spectra were the most consistent with the computed IR spectra for the lowest energy structures, in which deprotonation occurs at the carboxyl acid groups and all amide and carboxylate oxygen atoms are complexed to the metal cations. The N-H stretch band, observed at 3350 cm(-1) , is indicative of hydrogen bonding between the amine nitrogen atoms and the amide hydrogen atom. This study represents the first into large self-assembled multimetallic complexes bound by peptide ligands. PMID- 26279055 TI - Preliminary data on ASP2215: tolerability and efficacy in acute myeloid leukemia patients. AB - Claire Thom speaks to Gemma Westcott, Commissioning Editor: Claire Thom joined Astellas in 2013 as the Therapeutic Area Head for Oncology in Global Development. In that role, she also serves as the STAR leader for Oncology for Astellas. Prior to Astellas, she spent 12 years with Takeda. Her last position was Senior Vice President, Portfolio Management, Drug Development Management and Medical Informatics and Strategic Operations within the Medical Division (the Division within Millennium responsible for oncology clinical drug development within Takeda). During her 4 years at Millennium, at various times, she had responsibility within the Medical Division for leading portfolio management, business operations (medical finance, annual and mid-range financial planning, space planning and operations, headcount resourcing, development goals process), clinical development operations (clinical operations, programming, data management, statistics, medical writing, clinical outsourcing), drug development management (project management), medical informatics (technology support for the division) and the strategic project management office for the division. Prior to joining Millennium, Claire Thom spent 18 months working in Osaka, Japan, during which she was responsible for developing the oncology strategy for Takeda that culminated in the acquisition of Millennium. Before going to Japan, she held positions of varying responsibility within the Takeda US development organization including the management of regulatory affairs, safety, biometrics and data management, clinical research and quality assurance. Claire Thom has particular expertise in organizational design and efficiency; she has successfully worked through integrations across multiple functions and redesigned business processes. She has a PharmD from University of Illinois (IL, USA) and over 20 years of pharmaceutical experience including positions in medical affairs and new product planning (over 11 years at Searle) and drug development (over 12 years at Takeda/Millennium). PMID- 26279056 TI - Plasma Biomarkers of Inflammation, Endothelial Function and Hemostasis in Cerebral Small Vessel Disease. AB - BACKGROUND: The cause of lacunar ischemic stroke, a clinical feature of cerebral small vessel disease (SVD), is largely unknown. Inflammation and endothelial dysfunction have been implicated. Plasma biomarkers could provide mechanistic insights but current data are conflicting. White matter hyperintensities (WMHs) are an important imaging biomarker of SVD. It is unknown if plasma biomarkers add predictive capacity beyond age and vascular risk factors in explaining WMH. METHODS: We prospectively recruited patients presenting with non-disabling ischemic stroke, classifying them clinically and with the help of MRI as lacunar or cortical. We measured biomarkers of inflammation, endothelial dysfunction and hemostasis for >1 month after stroke and compared biomarker levels between stroke subtypes. We quantitatively calculated WMH. We used multiple linear regression analysis to model WMH as a function of age, sex, hypertension and smoking (the baseline model). We fitted exploratory models using plasma biomarkers as predictor variables to assess model improvement over baseline. RESULTS: We recruited 125 patients. The lacunar group (n = 65) had lower tissue plasminogen activator (t-PA) levels in unadjusted (7.39 vs. 8.59 ng/ml, p = 0.029) and adjusted (p = 0.035) analyses compared with the cortical group (n = 60). There were no significant differences in the other plasma biomarkers. The results for t PA were consistent with an updated meta-analysis, although the effect remains non significant (standardized mean difference -0.08 (95% CI -0.25 to 0.09)). The baseline regression model explained 29% of the variance in quantitative WMH (R2 0.289). Inflammatory biomarkers showed minor improvement over baseline (R2 0.291), but the other plasma biomarkers did not improve the baseline model. CONCLUSION: Plasma t-PA levels appear to differ between lacunar and cortical stroke subtypes, late after stroke, independent of age, sex and vascular risk factors and may reflect endothelial dysfunction. Except for a minor additional predictive effect of inflammatory markers, plasma biomarkers do not relate to WMH severity in this small stroke population. PMID- 26279057 TI - Perception, illusions and Bayesian inference. AB - Descriptive psychopathology makes a distinction between veridical perception and illusory perception. In both cases a perception is tied to a sensory stimulus, but in illusions the perception is of a false object. This article re-examines this distinction in light of new work in theoretical and computational neurobiology, which views all perception as a form of Bayesian statistical inference that combines sensory signals with prior expectations. Bayesian perceptual inference can solve the 'inverse optics' problem of veridical perception and provides a biologically plausible account of a number of illusory phenomena, suggesting that veridical and illusory perceptions are generated by precisely the same inferential mechanisms. PMID- 26279058 TI - Sleep Disorders Among People With Schizophrenia: Emerging Research. AB - Up to 80 % of individuals with schizophrenia spectrum disorders experience sleep disturbances, which impact physical and mental health, as well as quality of life. In this paper, we review and integrate emerging literature, published between 2012 and 2014, regarding approaches to diagnosis and treatment of major sleep disorders for people with schizophrenia spectrum disorders, including insomnia, obstructive sleep apnea (OSA), circadian rhythm dysfunction, and restless legs syndrome (RLS). We advocate for (1) the need to evaluate the utility of nonpharmacological approaches in people with schizophrenia spectrum disorders; (2) documentation of guidelines to assist providers in clinically tailoring such interventions when their clients experience positive, negative, and/or cognitive symptoms; (3) research on the best ways providers can capitalize on clients' self-identified needs and motivation to engage in sleep treatments through shared decision making; and (4) the importance of investigating whether and how mental health and sleep treatment services should be better connected to facilitate access for people with schizophrenia spectrum disorders. Assessment and tailored treatment of sleep disorders within mental health treatment settings has the potential to reduce sleep problems and improve functioning, quality of life, and recovery of this population. PMID- 26279059 TI - Predictive Factors for Time to Progression after Hyperthermic Mitomycin C Treatment for High-Risk Non-Muscle Invasive Urothelial Carcinoma of the Bladder: An Observational Cohort Study of 97 Patients. AB - INTRODUCTION: Hyperthermic mitomycin (HM) is a novel treatment modality for selected patients with high-risk non-muscle invasive bladder cancer (NMIBC). We sought to determine predictors of response to this therapy. PATIENTS AND METHODS: A longitudinal, cohort study of 97 patients with high-risk NMIBC treated with >=4 HM instillations on a prophylactic schedule was conducted. The primary outcome was time-to-progression survival; secondary outcomes were overall survival, cancer-specific survival, and adverse events. Descriptive statistics, Kaplan Meier survival analyses, Cox proportional hazards modelling, and univariate and multivariable regression were performed. RESULTS: The presence of initial complete response (CR; no evidence of disease at first check video-cystoscopy and urine cytology) post-HM treatment was an independent predictor of good response to HM. Female patients and those without carcinoma in situ (CIS) also appeared to respond better to the intervention. The overall bladder preservation rate at a median of 27 months was 81.4%; 17/97 (17.5%) patients died during the course of the study. CONCLUSIONS: High-risk NMIBC patients can be safely treated with HM and have good oncological outcome. However, those without an initial CR have a poor prognosis and should be counselled towards adopting other treatment methodologies such as cystectomy. Female gender and lack of CIS may be good prognostic indicators for response to HM. PMID- 26279060 TI - Pathophysiological evaluation of subacute ruminal acidosis (SARA) by continuous ruminal pH monitoring. AB - Evaluation of the radio-transmission pH-measurement system for monitoring the ruminal pH and subacute ruminal acidosis (SARA) in cattle is described. This is done in order to reveal the possible application of this system for detection and pathophysiological research of SARA by continuous ruminal pH measurement. The possibility of using this system for assessment of the ruminal pH in SARA cattle, and the presence of negative correlation between the ruminal pH and ruminal temperature in heathy and SARA cattle were determined. In addition, the 16S rRNA gene pyrosequencing analysis showed that the ruminal microbial community was simpler in SARA cattle, and the bacterial numbers in SARA cattle were lower than those in healthy hay-fed cattle. Concentrate feeding might have reduced the diversity of the ruminal microbial community. Changes in the ruminal microbial community of SARA cattle might be related to the changes in ruminal pH followed by the decrease in the number of some bacteria. Continuous monitoring of the ruminal pH using the radio-transmission pH-measurement system would be applied for detection and prevention of SARA in the field and pathophysiological research of SARA, including ruminal zymology and bacteriology, which have been determined previously by sampling of the ruminal fluid and measuring of ruminal pH. PMID- 26279061 TI - Early Upregulation of NLRP3 in the Brain of Neonatal Mice Exposed to Hypoxia Ischemia: No Early Neuroprotective Effects of NLRP3 Deficiency. AB - BACKGROUND: The NLRP3 inflammasome acts as an early mediator of inflammation by cleaving and releasing IL-1beta and IL-18 from their proforms. OBJECTIVE: The aim of this study was to describe NLRP3 activation and evaluate whether deficiency of NLRP3 protects against neonatal hypoxic ischemic brain damage. METHODS: C57BL/6 and NLRP3-/- mice at P9 were subjected to unilateral common carotid ligation followed by hypoxia. RT-PCR was used on mRNA in five different subregions of the brain. Brain infarction was evaluated by histopathology and 2,3,5 triphenyltetrazolium chloride staining. Plasma levels of IL-18 were measured by ELISA. Double labeling immunohistochemistry was used to examine cell-specific NLRP3 expression. RESULTS: NLRP3 was upregulated 24 h after hypoxia-ischemia (HI) in the hippocampus (2.6-fold), striatum (2.2-fold) and thalamus (2.3-fold). Brain infarction volumes were not statistically significantly different in NLRP3-/- mice compared to WT mice 24 h after HI, accompanied by no significant changes in plasma IL-18 levels. Three hours after HI, NLRP3 expression occurred in astrocytes located in the hippocampus and habenular nucleus of the thalamus. Microglia only showed scarce expression at this time point, but prominent NLRP3 expression 72 h after HI. CONCLUSION: Astrocytes are early mediators of NLRP3 activity. No early neuroprotective effect of NLRP3 deficiency in neonatal HI brain damage was shown. PMID- 26279063 TI - When the 'Ugly Duckling' Loses Brothers, It Becomes the 'Only Son of a Widowed Mother'. PMID- 26279062 TI - Comparison of microneedles and adhesive-tape stripping in skin preparation for epicutaneous allergen delivery. AB - BACKGROUND: Epicutaneous immunotherapy targets the network of dendritic cells in the epidermis. Allergen exposure of the dermal layers should be limited as these contain mast cells and blood vessels, which increases the risk for local and systemic allergic reactions. METHODS: This intraindividually controlled trial included 20 subjects with birch pollen allergy. Three areas of the volar forearms were treated by repeated adhesive-tape stripping, single-prick lancet piercing and microneedle array application. Four 10-fold dilutions of allergen extract were applied to each area and the IgE-mediated immediate-phase reactions and cell mediated eczema were assessed. RESULTS: Allergen application after tape stripping led to an immediate-phase reaction in 2 subjects (10%) at the highest allergen concentration of 10 HEP/ml. Both prick needle and microneedle pretreatment resulted in immediate-phase reactions in all subjects (100%). The reactivity pattern, however, differed significantly: 95% of the reactions after pricking occurred at concentrations of <=0.1 HEP/ml, whereas 50% of the reactions after microneedle preparation were noted at >=1 HEP/ml. In 3 subjects (15%), eczema was observed on the microneedle-treated skin area. No serious adverse events occurred. CONCLUSIONS: Microneedles enhance stratum corneum penetration when compared to tape stripping. However, they do not resolve the problem of mast cell mediated local reactions, possibly due to diffusion into the dermis. The occurrence of eczema after the microneedle treatment suggests induction of dendritic cell-mediated T cell responses. Therefore, skin preparation with microneedles may be a promising method for epicutaneous allergen immunotherapy. PMID- 26279064 TI - Optimized Plk1 PBD Inhibitors Based on Poloxin Induce Mitotic Arrest and Apoptosis in Tumor Cells. AB - Polo-like kinase 1 (Plk1) is a central regulator of mitosis and has been validated as a target for antitumor therapy. The polo-box domain (PBD) of Plk1 regulates its kinase activity and mediates the subcellular localization of Plk1 and its interactions with a subset of its substrates. Functional inhibition of the Plk1 PBD by low-molecular weight inhibitors has been shown to represent a viable strategy by which to inhibit the enzyme, while avoiding selectivity issues caused by the conserved nature of the ATP binding site. Here, we report structure activity relationships and mechanistic analysis for the first reported Plk1 PBD inhibitor, Poloxin. We present the identification of the optimized analog Poloxin 2, displaying significantly improved potency and selectivity over Poloxin. Poloxin-2 induces mitotic arrest and apoptosis in cultured human tumor cells at low micromolar concentrations, highlighting it as a valuable tool compound for exploring the function of the Plk1 PBD in living cells. PMID- 26279066 TI - Mitral valve repair in a Jehovah's witness with haemophilia A with high-titre inhibitor. PMID- 26279065 TI - NEURAPRO-E study protocol: a multicentre randomized controlled trial of omega-3 fatty acids and cognitive-behavioural case management for patients at ultra high risk of schizophrenia and other psychotic disorders. AB - AIM: Recent research has indicated that preventative intervention is likely to benefit patients 'at-risk' for psychosis, both in terms of symptom reduction and delay or prevention of onset of threshold psychotic disorder. The strong preliminary results for the effectiveness of omega-3 polyunsaturated fatty acids (PUFAs), coupled with the falling transition rate in ultra high-risk (UHR) samples, mean that further study of such benign, potentially neuroprotective interventions is clinically and ethically required. Employing a multicentre approach, enabling a large sample size, this study will provide important information with regard to the use of omega-3 PUFAs in the UHR group. METHODS: This trial is a 6-month, double-blind, randomized placebo-controlled trial of 1.4 g day-1 omega-3 PUFAs in UHR patients aged between 13 and 40 years. The primary hypothesis is that UHR patients receiving omega-3 PUFAs plus cognitive behavioural case management (CBCM) will be less likely to transition to psychosis over a 6-month period compared to treatment with placebo plus CBCM. Secondary outcomes will examine symptomatic and functional changes, as well as examine if candidate risk factors predict response to omega-3 PUFA treatment in the UHR group. CONCLUSION: This is the protocol of the NeuraproE study. Utilizing a large sample, results from this study will be important in informing indicated prevention strategies for schizophrenia and other psychotic disorders, which may be the strongest avenue for reducing the burden, stigmatization, disability and economic consequences of these disorders. PMID- 26279067 TI - Gene Therapy for Retinal Disease: What Lies Ahead. AB - Gene therapy in simple terms can be defined as a medical treatment that exerts its effects using molecules of DNA or RNA within cells. Most traditional drugs act by mechanisms that include binding to cell surface receptors, inhibiting enzymes in intracellular pathways or by modifying transcription. These approaches rely to some extent on a normal genetic make-up of the cell in the final common pathway, which raises significant challenges in diseases that are caused by specific gene mutations. An alternative gene therapy approach to change the behaviour of cells at the most fundamental level by one single genetic modification is therefore potentially very powerful and wide ranging. This paper presents an overview of retinal gene therapy at the current time and highlights the future therapeutic potential for a number of diseases that are currently incurable. PMID- 26279068 TI - Tissue Inhibitor of Metalloproteinase-1: Actions beyond Matrix Metalloproteinase Inhibition. PMID- 26279069 TI - Room for caring: patients' experiences of well-being, relief and hope during serious illness. AB - AIM: This study explores how seriously ill hospitalized patients' experience and assign meaning to their patient room. BACKGROUND: Modern hospitals and the rational underlying care and treatment of today have their emphasis on diagnosis, cure and treatment. Consequently, aesthetics in the patient rooms such as a view of nature or natural light entering the room are often neglected in caring for these patients. METHOD: A phenomenological-hermeneutic study design was applied and data was collected through multiple qualitative interviews combined with observations at a teaching hospital in Denmark. Twelve patients participated. FINDINGS: The findings show that a view of nature and natural light in the form of sunlight or daylight in the patient room play a significant role in creating positive and supportive thoughts and emotions in the seriously ill patients. Three themes were identified: (i) Experiencing inner peace and an escape from negative thoughts, (ii) Experiencing a positive mood and hope and (iii) Experiencing good memories. CONCLUSION: Our findings highlight aesthetic sensory impressions in the form of nature sights and natural light in the patient room as a powerful source of well-being, relief and hope for the patients during serious illness. Therefore, these sensory impressions should be thought of as holding palliative potential and should be included as a part of caring for the seriously ill patients. PMID- 26279071 TI - HIV risk and sense of community: French gay male discourses on barebacking. AB - This paper analyses the use of the concept of 'barebacking' as a risk category in the discourses of French gay men. It discusses how the rise and spread of the term barebacking contributes to reframing gay men's personal experiences of HIV prevention and their sense of belonging (or a lack thereof) to a gay community. The study is based on 30 qualitative interviews with French gay men conducted between 2005 and 2008. An import from the USA, the term barebacking emerged publicly in France in the late-1990s and was first used to describe intentionally unprotected sexual practices. Debates surrounding this risk category were marked by violent controversy over its use and its definition among HIV prevention actors. There remains a general lack of consensus on the definition of the term, despite its use by activists, in porn culture and in the daily discourses of gay men. By focusing on the relational roots of risk perception, I consider how uses of the term barebacking invoke a moral framework around risk taking. PMID- 26279070 TI - White-Coat Effect Among Older Adults: Data From the Jackson Heart Study. AB - Many adults with elevated clinic blood pressure (BP) have lower BP when measured outside the clinic. This phenomenon, the "white-coat effect," may be larger among older adults, a population more susceptible to the adverse effects of low BP. The authors analyzed data from 257 participants in the Jackson Heart Study with elevated clinic BP (systolic/diastolic BP [SBP/DBP] >=140/90 mm Hg) who underwent ambulatory BP monitoring (ABPM). The white-coat effect for SBP was larger for participants 60 years and older vs those younger than 60 years in the overall population (12.2 mm Hg, 95% confidence interval [CI], 9.2-15.1 mm Hg and 8.4 mm Hg, 95% CI, 5.7-11.1, respectively; P=.06) and among those without diabetes or chronic kidney disease (15.2 mm Hg, 95% CI, 10.1-20.2 and 8.6 mm Hg, 95% CI, 5.0 12.3, respectively; P=.04). After multivariable adjustment, clinic SBP >=150 mm Hg vs <150 mm Hg was associated with a larger white-coat effect. Studies are needed to investigate the role of ABPM in guiding the initiation and titration of antihypertensive treatment, especially among older adults. PMID- 26279072 TI - The efficacy of 308 nm UV excimer light as monotherapy and combination therapy with topical khellin 4% and/or tacrolimus 0.1% in the treatment of vitiligo. PMID- 26279073 TI - Chromium Supplementation and the Effects on Metabolic Status in Women with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. AB - BACKGROUND: The aim of the present study was to evaluate the beneficial effects of chromium intake on markers of insulin metabolism and lipid profiles in women with polycystic ovary syndrome (PCOS). METHODS: In a prospective, randomized, double-blind, placebo-controlled trial, 64 women with PCOS were randomized to receive 200 ug chromium picolinate supplements (n = 32) or placebo (n = 32) for 8 weeks. Fasting blood samples were obtained at baseline and 8 weeks after the intervention to quantify markers of insulin metabolism and lipid concentrations. RESULTS: Chromium supplementation in women with PCOS resulted in significant decreases in serum insulin levels (-3.6 +/- 7.4 vs. +3.6 +/- 6.2 uIU/ml, p < 0.001), homeostasis model of assessment-insulin resistance (HOMA-IR; -0.8 +/- 1.6 vs. +0.9 +/- 1.5, p < 0.001), homeostatic model assessment-beta cell function (HOMA-B; -15.5 +/- 32.3 vs. +13.6 +/- 23.1, p < 0.001), and a significant increase in quantitative insulin sensitivity check index (QUICKI) score (+0.02 +/ 0.03 vs. -0.008 +/- 0.02, p = 0.001) compared with the placebo. In addition, a trend toward a significant effect of chromium supplementation on decreasing serum triglycerides (-12.4 +/- 74.4 vs. +15.2 +/- 32.4 mg/dl, p = 0.05), very low density lipoprotein-cholesterol (-2.5 +/- 14.9 vs. +3.0 +/- 6.5 mg/dl, p = 0.05), and cholesterol concentrations (-8.6 +/- 21.9 vs. +0.7 +/- 22.4 mg/dl, p = 0.09) was seen. CONCLUSIONS: Eight weeks of chromium supplementation among PCOS women had favorable effects on markers of insulin metabolism. PMID- 26279074 TI - Motional narrowing under diffusion of two spin sub-lattices in LiNaSO4. AB - An expression for the dipolar correlation function characterizing the fluctuations of the Hamiltonian under uncorrelated diffusion of two cationic sub lattices in a solid has been obtained. A corresponding formula, which can be used for fitting the two-step temperature dependencies of the NMR line width, has been deduced. We also considered the case of a distribution of correlation times and deduced a corresponding analytical fitting function. Elaborated expressions have been applied to the NMR line width analysis of LiNaSO4 in the temperature range 295-788 K. PMID- 26279075 TI - Retrospective Rescreening of Negative Cervical Cytology Samples Preceding Histologically Proven CIN2-3 and Squamous Cell Carcinoma: An Educational Opportunity to Understand and Prevent Laboratory Errors. AB - OBJECTIVES: We aimed to analyze the false-negative (FN) liquid-based cytology diagnoses from the 5 years preceding all the 2013 histologically proven cervical intraepithelial neoplasia (CIN)2-3 and squamous cell carcinoma (SCC) and to propose corrective actions. STUDY DESIGN: This was a retrospective, blinded rescreening ('5-year look-back') of liquid-based cytology samples with negative categorizations, which occurred before histologically proven CIN2-3 and SCC. RESULTS: The FN rate was 7.8% (21/256 samples preceding CIN2-3 and 0/13 samples preceding SCC). Slides confirmed as 'negative', 'interpretation error' and 'screening error', respectively, were 3.3% (9/269), 2.6% (7/269) and 1.9% (5/269). In 9/12 cases, error was associated with small atypical cells. In 7/12 cases, these diagnostic cells were less than 5/10 HPF. Inflammation and prominent reactive changes were present in 5/12 cases. Five patients had a positive clinical history. In 2 cases, there were multiple-cell-layer artifacts. Dense groups of small blue atypical cells were missed in 2 other cases. Dotting was imprecise in 6/7 samples. CONCLUSION: Considering the above results, we specifically reoriented our continuous education activities, focusing rapid rescreening on scanty, isolated, small, atypical cells and dense cell groups. Prior to final diagnosis, pathologists should systematically review the entire surface of the dotted slides, with special attention being devoted to slides with multiple cell layers and tridimensional groups. PMID- 26279077 TI - Influences of Different Doses of Midazolam on Mother and Fetus in Fetoscopic Surgery for Twin-to-Twin Transfusion Syndrome. AB - OBJECTIVE: We observed influences of different doses of intravenous midazolam on mother and fetus in fetoscopic surgery for twin-to-twin transfusion syndrome (TTTS). METHODS: A total of 18 pregnant women with TTTS were randomly divided into groups M1 and M2 according to differing doses of midazolam. Some parameters were respectively recorded as prior to administration of midazolam (T0), instantly after anesthesia induction (T1), at incision (T2), instantly after laser coagulation (T3) and at the end of surgery (T4). RESULTS: There was no statistical difference in oxygen saturation and respiratory rate between groups M1 and M2 (all p > 0.05); but mean arterial pressure, heart rate, anxiety visual analog test, Observer's Assessment of Alertness/Sedation scale values and Kreb's scores were significantly lower in group M2 than in group M1 from T1 to T4 (all p < 0.05). In both groups, there was no fetal movement during laser coagulation. CONCLUSION: We propose that the appropriate dose for midazolam be 0.02 mg/kg in fetoscopic surgery for TTTS. PMID- 26279080 TI - Well-Being Therapy in the Netherlands. PMID- 26279078 TI - Intergenerational Transmission of Stress in Humans. AB - The hypothesis that offspring are affected by parental trauma or stress exposure, first noted anecdotally, is now supported empirically by data from Holocaust survivor offspring cohorts and other populations. These findings have been extended to less extreme forms of stress, where differential physical, behavioral, and cognitive outcomes are observed in affected offspring. Parental stress-mediated effects in offspring could be explained by genetics or social learning theory. Alternatively, biological variations stemming from stress exposure in parents could more directly have an impact on offspring, a concept we refer to here as 'intergenerational transmission', via changes to gametes and the gestational uterine environment. We further extend this definition to include the transmission of stress to offspring via early postnatal care, as animal studies demonstrate the importance of early maternal care of pups in affecting offsprings' long-term behavioral changes. Here, we review clinical observations in offspring, noting that offspring of stress- or trauma-exposed parents may be at greater risk for physical, behavioral, and cognitive problems, as well as psychopathology. Furthermore, we review findings concerning offspring biological correlates of parental stress, in particular, offspring neuroendocrine, epigenetic, and neuroanatomical changes, in an attempt to determine the extent of parental stress effects. Although understanding the etiology of effects in offspring is currently impeded by methodological constraints, and limitations in our knowledge, we summarize current information and conclude by presenting hypotheses that have been prompted by recent studies in the field. PMID- 26279079 TI - Bidirectional Modulation of Alcohol-Associated Memory Reconsolidation through Manipulation of Adrenergic Signaling. AB - Alcohol addiction is a problem of great societal concern, for which there is scope to improve current treatments. One potential new treatment for alcohol addiction is based on disrupting the reconsolidation of the maladaptive Pavlovian memories that can precipitate relapse to drug-seeking behavior. In alcohol self administering rats, we investigated the effects of bidirectionally modulating adrenergic signaling on the strength of a Pavlovian cue-alcohol memory, using a behavioral procedure that isolates the specific contribution of one maladaptive Pavlovian memory to relapse, the acquisition of a new alcohol-seeking response for an alcohol-associated conditioned reinforcer. The beta-adrenergic receptor antagonist propranolol, administered in conjunction with memory reactivation, persistently disrupted the memory that underlies the capacity of a previously alcohol-associated cue to act as a conditioned reinforcer. By contrast, enhancement of adrenergic signaling by administration of the adrenergic prodrug dipivefrin at reactivation increased the strength of the cue-alcohol memory and potentiated alcohol seeking. These data demonstrate the importance of adrenergic signaling in alcohol-associated memory reconsolidation, and suggest a pharmacological target for treatments aiming to prevent relapse through the disruption of maladaptive memories. PMID- 26279081 TI - Strategies to Improve Bioavailability and In Vivo Efficacy of the Endogenous Opioid Peptides Endomorphin-1 and Endomorphin-2. AB - Morphine and the other alkaloids found in the opium poppy plant still represent the preferred therapeutic tools to treat severe pain in first aid protocols, as well as chronic pain. The use of the opiate alkaloids is accompanied by several unwanted side effects; additionally, some forms of pain are resistant to standard treatments (e.g. neuropathic pain from cancer). For these reasons, there is currently renewed interest in the design and assay of modified versions of the potent endogenous opioid peptides endomorphin-1 and endomorphin-2. This review presents a selection of the strategies directed at preparing highly stable peptidomimetics of the endomorphins, and of the strategies aimed at improving central nervous system bioavailability, for which increased in vivo antinociceptive efficacy was clearly demonstrated. PMID- 26279082 TI - Improving Peptide Applications Using Nanotechnology. AB - Peptides are being successfully used in various fields including therapy and drug delivery. With advancement in nanotechnology and targeted delivery carrier systems, suitable modification of peptides has enabled achievement of many desirable goals over-riding some of the major disadvantages associated with the delivery of peptides in vivo. Conjugation or physical encapsulation of peptides to various nanocarriers, such as liposomes, micelles and solid-lipid nanoparticles, has improved their in vivo performance multi-fold. The amenability of peptides to modification in chemistry and functionalization with suitable nanocarriers are very relevant aspects in their use and have led to the use of 'smart' nanoparticles with suitable linker chemistries that favor peptide targeting or release at the desired sites, minimizing off-target effects. This review focuses on how nanotechnology has been used to improve the number of peptide applications. The paper also focuses on the chemistry behind peptide conjugation to nanocarriers, the commonly employed linker chemistries and the several improvements that have already been achieved in the areas of peptide use with the help of nanotechnology. PMID- 26279083 TI - Conformal Visualization for Partially-Immersive Platforms. AB - Current immersive VR systems such as the CAVE provide an effective platform for the immersive exploration of large 3D data. A major limitation is that in most cases at least one display surface is missing due to space, access or cost constraints. This partially-immersive visualization results in a substantial loss of visual information that may be acceptable for some applications, however it becomes a major obstacle for critical tasks, such as the analysis of medical data. We propose a conformal deformation rendering pipeline for the visualization of datasets on partially-immersive platforms. The angle-preserving conformal mapping approach is used to map the 360 degrees 3D view volume to arbitrary display configurations. It has the desirable property of preserving shapes under distortion, which is important for identifying features, especially in medical data. The conformal mapping is used for rasterization, realtime raytracing and volume rendering of the datasets. Since the technique is applied during the rendering, we can construct stereoscopic images from the data, which is usually not true for image-based distortion approaches. We demonstrate the stereo conformal mapping rendering pipeline in the partially-immersive 5-wall Immersive Cabin (IC) for virtual colonoscopy and architectural review. PMID- 26279084 TI - Bioinformatics Annotation of Human Y Chromosome-Encoded Protein Pathways and Interactions. AB - We performed a comprehensive analysis of human Y chromosome-encoded proteins, their pathways, and their interactions using bioinformatics tools. From the NCBI annotation release 107 of human genome, we retrieved a total of 66 proteins encoded on Y chromosome. Most of the retrieved proteins were also matched with the proteins listed in the core databases of the Human Proteome Project including neXtProt, PeptideAtlas, and the Human Protein Atlas. When we examined the pathways of human Y-encoded proteins through KEGG database and Pathway Studio software, many of proteins fall into the categories related to cell signaling pathways. Using the STRING program, we found a total of 49 human Y-encoded proteins showing strong/medium interaction with each other. While using the Pathway studio software, we found that a total of 16 proteins interact with other chromosome-encoded proteins. In particular, the SRY protein interacted with 17 proteins encoded on other chromosomes. Additionally, we aligned the sequences of human Y-encoded proteins with the sequences of chimpanzee and mouse Y-encoded proteins using the NCBI BLAST program. This analysis resulted in a significant number of orthologous proteins between human, chimpanzee, and mouse. Collectively, our findings provide the scientific community with additional information on the human Y chromosome-encoded proteins. PMID- 26279085 TI - The growth scale and kinetics of WS2 monolayers under varying H2 concentration. AB - The optical and electronic properties of tungsten disulfide monolayers (WS2) have been extensively studied in the last few years, yet growth techniques for WS2 remain behind other transition metal dichalcogenides (TMDCs) such as MoS2. Here we demonstrate chemical vapor deposition (CVD) growth of continuous monolayer WS2 films on mm(2) scales and elucidate effects related to hydrogen (H2) gas concentration during growth. WS2 crystals were grown by reduction and sulfurization of WO3 using H2 gas and sulfur evaporated from solid sulfur powder. Several different growth formations (in-plane shapes) were observed depending on the concentration of H2. Characterization using atomic force microscopy (AFM) and scanning electron microscopy (SEM) revealed etching of the SiO2 substrate at low concentrations of H2 and in the presence of an Ar carrier gas. We attribute this to insufficient reduction of WO3 during growth. High H2 concentrations resulted in etching of the grown WS2 crystals after growth. The two dimensional X-ray diffraction (2D XRD) pattern demonstrates that the monolayer WS2 was grown with the (004) plane normal to the substrate, showing that the WS2 conforms to the growth substrate. PMID- 26279086 TI - Pictorial review. Magnetic resonance for radiotherapy management and treatment planning in prostatic carcinoma. AB - MRI has an important role for radiotherapy (RT) treatment planning in prostate cancer (PCa) providing accurate visualization of the dominant intraprostatic lesion (DIL) and locoregional anatomy, assessment of local staging and depiction of implanted devices. MRI enables the radiation oncologist to optimize RT planning by better defining target tumour volumes (thereby increasing local tumour control), as well as decreasing morbidity (by minimizing the dose to adjacent normal structures). Using MRI, radiation oncologists can define the DIL for delivery of boost doses of RT using a variety of techniques including: stereotactic body radiotherapy, intensity-modulated radiotherapy, proton RT or brachytherapy to improve tumour control. Radiologists require a familiarity with the different RT methods used to treat PCa, as well as an understanding of the advantages and disadvantages of the various MR pulse sequences available for RT planning in order to provide an optimal multidisciplinary RT treatment approach to PCa. Understanding the expected post-RT appearance of the prostate and typical characteristics of local tumour recurrence is also important because MRI is rapidly becoming an integral component for diagnosis, image-guided histological sampling and treatment planning in the setting of biochemical failure after RT or surgery. PMID- 26279087 TI - Development of a low-dose protocol for cone beam CT examinations of the anterior maxilla in children. AB - OBJECTIVE: The aim of this study was to develop a low-dose protocol suitable for cone beam CT (CBCT) examination of an impacted maxillary canine in children by using a combination of dosimetry with subjective and objective image quality assessment. METHODS: Radiation dose and image quality measurements were made using a dental CBCT machine. An image quality phantom was used to investigate the relationship between objective image quality and dose-area product (DAP) for a broad range of exposure settings. Subjective image quality assessment was achieved using a paediatric skull phantom submerged in a water bath for the same range of exposure settings. Eight clinicians assessed each CBCT data set for nine aspects of image quality using a five-point rating scale of agreement. RESULTS: Acceptable image quality, defined using subjective judgements by the clinicians of the skull phantom images, was achievable with DAP values of 127 mGy cm(2) or greater and a polytetrafluoroethylene (PTFE) contrast-to-noise ratio (CNR) of 4.8 or greater. A cautious choice was made to recommend a low-dose protocol of 80 kV and 3 mA for implementation into clinical practice, corresponding to a DAP value of 146 mGy cm(2) and a PTFE CNR of 5.0. CONCLUSION: A low-dose protocol for this particular CBCT machine was established which represents as much as a 50% reduction compared with manufacturer's recommendations. ADVANCES IN KNOWLEDGE: To the authors' best knowledge, this is the first study that addresses dose optimization in paediatric clinical protocols in dental CBCT. Furthermore, this study explores the relationship between radiation dose, objective and subjective image quality. PMID- 26279088 TI - Recurrent takotsubo cardiomyopathy in a child. AB - Takotsubo cardiomyopathy or transient apical ballooning syndrome very rarely presents in children. In all patients with takotsubo, it is estimated that only 3.5% will have recurrence. In this study, we describe a case of recurrent takotsubo cardiomyopathy in a child, likely triggered by status epilepticus. PMID- 26279089 TI - Claudin 1 Promotes Migration and Increases Sensitivity to Tamoxifen and Anticancer Drugs in Luminal-like Human Breast Cancer Cells MCF7. AB - Downregulation of claudin 1, a critical tight junction protein, has been correlated with increased invasiveness in breast cancer. However, recent studies suggest that claudin 1 contributes to the progression of some molecular subtypes of breast cancer. In this study, claudin 1 promotes migration in luminal-like MCF7 human breast cancer cells and increases their sensitivity to tamoxifen, etoposide, and cisplatin. We also observed an inverse relationship between upregulation of claudin 1 and TGFbeta. Collectively, our results suggest that claudin 1 has the potential to be used as a predictive marker for treatment efficacy for specific breast cancer patient subgroups. PMID- 26279090 TI - Magma injection beneath the urban area of Naples: a new mechanism for the 2012 2013 volcanic unrest at Campi Flegrei caldera. AB - We found the first evidence, in the last 30 years, of a renewed magmatic activity at Campi Flegrei caldera from January 2012 to June 2013. The ground deformation, observed through satellite interferometry and GPS measurements, have been interpreted as the effect of the intrusion at shallow depth (3090 +/- 138 m) of 0.0042 +/- 0.0002 km(3) of magma within a sill. This interrupts about 28 years of dominant hydrothermal activity and occurs in the context of an unrest phase which began in 2005 and within a more general ground uplift that goes on since 1950. This discovery has implications on the evaluation of the volcanic risk and in the volcanic surveillance of this densely populated area. PMID- 26279091 TI - Effect of in-office bleaching with 35% hydrogen peroxide with and without addition of calcium on the enamel surface. AB - This study aimed to evaluate effectiveness and effects of bleaching with 35% hydrogen peroxide with and without calcium on color, micromorphology, and the replacement of calcium and phosphate on the enamel surface. Thirty bovine enamel blocks (5.0 * 5.0 mm) were placed into the following groups: G1: artificial saliva (control); G2: 35% hydrogen peroxide gel without calcium (Whiteness HP Maxx-FGM); and G3: 35% hydrogen peroxide gel with calcium (Whiteness HP Blue FGM). Three color measurements were performed with a spectrophotometer: untreated (baseline), after performing staining, and after application of bleaching agents. Calcium deposition on the enamel was evaluated before and after the application of bleaching agents using energy-dispersive X-ray spectrometry. The enamel surface micromorphology was observed under scanning electron microscopy. The pH of each product was measured. The data were subjected to one-factor analysis of variance (ANOVA), and any differences were analyzed using Tukey's test (P < 0.05). G3 showed greater variation in total color after the experiment than G2 and G1; there was no significant difference in calcium or phosphorus concentration before and after the experimental procedures; morphological changes were observed only in G2 and G3; and the pH values of the Whiteness HP Maxx and Whiteness HP Blue bleaching agents were 5.77 and 7.79, respectively. The 35% hydrogen peroxide with calcium showed greater bleaching potential, but the addition of calcium had no effect in terms of reducing morphological changes or increasing the calcium concentration on the enamel surface. PMID- 26279092 TI - R2O3 (R = La, Y) modified erbium activated germanate glasses for mid-infrared 2.7 MUm laser materials. AB - Er(3+) activated germanate glasses modified by La2O3 and Y2O3 with good thermal stability were prepared. 2.7 MUm fluorescence was observed and corresponding radiative properties were investigated. A detailed discussion of J-O parameters has been carried out based on absorption spectra and Judd-Ofelt theory. The peak emission cross sections of La2O3 and Y2O3 modified germanate glass are (14.3 +/- 0.10) * 10(-21) cm(2) and (15.4 +/- 0.10) * 10(-21) cm(2), respectively. Non radiative relaxation rate constants and energy transfer coefficients of (4)I11/2 and (4)I13/2 levels have been obtained and discussed to understand the 2.7 MUm fluorescence behavior. Moreover, the energy transfer processes of (4)I11/2 and (4)I13/2 level were quantitatively analyzed according to Dexter's theory and Inokuti-Hirayama model. The theoretical calculations are in good agreement with the observed 2.7 MUm fluorescence phenomena. Results demonstrate that the Y2O3 modified germanate glass, which possesses more excellent spectroscopic properties than La2O3 modified germanate glass, might be an attractive candidate for mid infrared laser. PMID- 26279093 TI - Developing a Tabletop Exercise to Test Community Resilience: Lessons from the Los Angeles County Community Disaster Resilience Project. AB - OBJECTIVE: We aimed to develop and test a community resilience tabletop exercise to assess progress in community resilience and to provide an opportunity for quality improvement and capacity building. METHODS: A tabletop exercise was developed for the Los Angeles County Community Disaster Resilience (LACCDR) project by using an extended heat wave scenario with health and infrastructure consequences. The tabletop was administered to preparedness only (control) and resilience (intervention) coalitions during the summer of 2014. Each exercise lasted approximately 2 hours. The coalitions and LACCDR study team members independently rated each exercise to assess 4 resilience levers (partnership, engagement, self-sufficiency, and education). Resilience coalitions received more detailed feedback in the form of recommendations for improvement. RESULTS: The resilience coalitions performed the same or better than the preparedness coalitions on the partnership and self-sufficiency levers. Most coalitions did not have enough (both quantity and type) of the partner organizations needed for an escalating heat wave or changing conditions or enough engagement of organizations representing at-risk populations. Coalitions also lacked educational materials to cover topics as far ranging as heat to power outages to psychological impacts of disaster. CONCLUSION: A tabletop exercise can be used to stress and test resilience-based capacities, with particular attention to a community's ability to leverage a range of partnerships and other assets to confront a slowly evolving but multifactorial emergency. PMID- 26279094 TI - Metagenomic and metaproteomic analyses of Accumulibacter phosphatis-enriched floccular and granular biofilm. AB - Biofilms are ubiquitous in nature, forming diverse adherent microbial communities that perform a plethora of functions. Here we operated two laboratory-scale sequencing batch reactors enriched with Candidatus Accumulibacter phosphatis (Accumulibacter) performing enhanced biological phosphorus removal. Reactors formed two distinct biofilms, one floccular biofilm, consisting of small, loose, microbial aggregates, and one granular biofilm, forming larger, dense, spherical aggregates. Using metagenomic and metaproteomic methods, we investigated the proteomic differences between these two biofilm communities, identifying a total of 2022 unique proteins. To understand biofilm differences, we compared protein abundances that were statistically enriched in both biofilm states. Floccular biofilms were enriched with pathogenic secretion systems suggesting a highly competitive microbial community. Comparatively, granular biofilms revealed a high stress environment with evidence of nutrient starvation, phage predation pressure, and increased extracellular polymeric substance and cell lysis. Granular biofilms were enriched in outer membrane transport proteins to scavenge the extracellular milieu for amino acids and other metabolites, likely released through cell lysis, to supplement metabolic pathways. This study provides the first detailed proteomic comparison between Accumulibacter-enriched floccular and granular biofilm communities, proposes a conceptual model for the granule biofilm, and offers novel insights into granule biofilm formation and stability. PMID- 26279096 TI - Good News for Valve-Sparing Surgery in Marfan Syndrome. PMID- 26279097 TI - Multiple Arterial Coronary Bypass Grafting: Likely Better, But Not Yet a Mandate. PMID- 26279095 TI - A combination hydrogel microparticle-based vaccine prevents type 1 diabetes in non-obese diabetic mice. AB - Targeted delivery of self-antigens to the immune system in a mode that stimulates a tolerance-inducing pathway has proven difficult. To address this hurdle, we developed a vaccine based-approach comprised of two synthetic controlled-release biomaterials, poly(lactide-co-glycolide; PLGA) microparticles (MPs) encapsulating denatured insulin (key self-antigen in type 1 diabetes; T1D), and PuraMatrix(TM) peptide hydrogel containing granulocyte macrophage colony-stimulating factor (GM CSF) and CpG ODN1826 (CpG), which were included as vaccine adjuvants to recruit and activate immune cells. Although CpG is normally considered pro-inflammatory, it also has anti-inflammatory effects, including enhancing IL-10 production. Three subcutaneous administrations of this hydrogel (GM-CSF/CpG)/insulin-MP vaccine protected 40% of NOD mice from T1D. In contrast, all control mice became diabetic. In vitro studies indicate CpG stimulation increased IL-10 production, as a potential mechanism. Multiple subcutaneous injections of the insulin containing formulation resulted in formation of granulomas, which resolved by 28 weeks. Histological analysis of these granulomas indicated infiltration of a diverse cadre of immune cells, with characteristics reminiscent of a tertiary lymphoid organ, suggesting the creation of a microenvironment to recruit and educate immune cells. These results demonstrate the feasibility of this injectable hydrogel/MP based vaccine system to prevent T1D. PMID- 26279098 TI - Malignant Middle Cerebral Artery Infarction Resulting from Dissection of Middle Cerebral Artery. AB - A 30-year-old man presented with headache, left hemiparesis, and uncal herniation. Magnetic resonance imaging showed acute infarction in the right middle cerebral artery (MCA). Lifesaving craniotomy proceeded because of the uncal herniation. Assessment of brain tissue led to a diagnosis of MCA dissection. His skin biopsy showed ultrastructural abnormalities of dermal connective tissue. This is the unique case that dissection was diagnosed from both a biopsy specimen of the MCA and the dermal connective tissue. PMID- 26279099 TI - E-Cigarettes: Youth and Trends in Vaping. PMID- 26279100 TI - Testicular hypertrophy as a predictor for contralateral monorchism: Retrospective review of prospectively recorded data. AB - OBJECTIVES: Testicular hypertrophy has previously been evaluated as a predictor of monorchism. However, its implication in clinical practice is not well evaluated. The aim of the present study was to examine its value in planning the operative time. PATIENTS AND METHODS: Medical charts of prospectively recorded data of 76 consecutive patients with unilateral impalpable testis from 2011 to 2014 were reviewed at the present institute. Inclusion criteria included prepubertal patients with non-palpable testes by examination under anesthesia. Contralateral testes were prospectively measured using a Takihara orchidometer. Orchiectomy or orchiopexy was performed according to the viability of the undescended testis (UDT). Collected data included age of surgery, contralateral testicular size, surgical time and laparoscopic findings. A ROC curve was used to define the best cut-off volume of the contralateral testis that can predict ipsilateral testicular viability. The Student's t-test was used to examine if this cut-off volume would be useful in allocating the operative time. RESULTS: Of 76 patients, four palpable testes by examination under anesthesia were excluded. The remaining 72 patients were included in the study. Ipsilateral normal viable testes were found in 26 (36.1%) patients, while 46 (63.9%) had non-viable testes (testicular nubbins or vanishing testes) (Figure). A contralateral testicular volume > 2 ml was significantly predictive for monorchism with 71.7% sensitivity and 100% specificity (P < 0.001). The mean operative time for management of UDT with a contralateral size >2 ml was 50 min, which was significantly shorter than that for UDT with a contralateral size <= 2 ml, which was 88 min (P < 0.001). DISCUSSION: In previously published reports, the cut-off value for testicular hypertrophy that predicts monorchism greatly varied. This is likely due to the different methods used for testicular measurements that make it impractical to make a direct comparison. The usefulness of predicting monorchism before surgery has not previously been used as a guide for allocating operative time in the management of a unilateral non-palpable testicle. This study had some limitations, including a relatively small sample size and involvement of different surgeons, which may have affected the operative time. CONCLUSION: Using the cut-off volume of a contralateral testis >2 ml as a predictor for monorchism can reduce the allocated operative time by approximately one third. PMID- 26279101 TI - Is renal scintigraphy necessary after heminephrectomy in children? AB - INTRODUCTION: Heminephrectomy remains an excellent option for a poorly functioning moiety in a duplicated collecting system. A primary concern during heminephrectomy is the potential for a significant functional loss in the remaining ipsilateral moiety. As the gold standard for the assessment of differential renal function, renal scintigraphy is often used in the postoperative evaluation of children undergoing heminephrectomy. However, this imaging modality is costly, invasive, and associated with exposure to radiation. Doppler renal ultrasound (RUS) avoids these concerns and is able to evaluate for structural and functional abnormalities. OBJECTIVE: The present study sought to compare Doppler RUS to renal scintigraphy in determining the viability of the remaining ipsilateral moiety in children who underwent heminephrectomy for a poorly functioning moiety in a duplicated collecting system. MATERIALS AND METHODS: The institutional database of children who underwent open heminephrectomy for a poorly functioning moiety in a duplicated collecting system between 2006 and 2013 was reviewed. Only children who underwent both a postoperative Doppler RUS and renal scan were included. A blinded pediatric radiologist independently reviewed all Doppler RUS. Vascular flow on Doppler RUS was correlated with the preservation of renal function in the remaining ipsilateral moiety on renal scintigraphy. RESULTS: A total of 29 children were identified for inclusion. Demographic and operative data are provided in Table. The average pre-operative and postoperative differential renal function in the ipsilateral kidney was 41.6% and 38% on renal scintigraphy, respectively, for an average decrease of 3.6% (-18% to +12%). Doppler RUS demonstrated the presence of vascular flow to the remaining ipsilateral moieties of all children after heminephrectomy. Renal scintigraphy confirmed the viability of these moieties in all children. DISCUSSION: The first study comparing Doppler RUS to renal scintigraphy was performed to determine the viability of the remaining ipsilateral moiety after heminephrectomy. While no cases of complete functional loss were observed, an average decrease of 3.6% in the ipsilateral renal function favorably compared with other series of children undergoing open heminephrectomy. The limitations of the study included its retrospective design at a single institution. The interpretation of Doppler RUS by an individual pediatric radiologist may also have lead to interobserver variability and impacted the reproducibility of the study, while the absence of any cases of complete functional loss may have impacted its generalizability. CONCLUSIONS: Doppler RUS is an accurate imaging modality for determining the viability of the remaining ipsilateral moiety after heminephrectomy and may obviate the need for renal scintigraphy. PMID- 26279102 TI - Proximal hypospadias: A persistent challenge. Single institution outcome analysis of three surgical techniques over a 10-year period. AB - INTRODUCTION: The optimal treatment of proximal hypospadias remains controversial. Several techniques have been described, but the best approach remains unsettled. OBJECTIVE: To evaluate and compare the complication rates of proximal hypospadias with and without ventral curvature (VC), according to three different surgical techniques: tubularized incised plate (TIP) uretroplasty, dorsal inlay graft TIP (DIG), and staged preputial repair (SR). It was hypothesized that SR performs better than TIP and DIG for proximal hypospadias. METHODS: Single-center, retrospective chart review of all patients with primary proximal hypospadias reconstructed between 2003 and 2013. The DIG was selectively employed in cases with narrow urethral plate (UP) and deficient spongiosum. Extensive urethral plate (UP) mobilization (UPM), dorsal plication (DP) and/or deep transverse incisions of tunica albuginea (DTITA) were selectively performed when attempting to spare transecting the UP. Division of UP and SR was favored in cases with severe VC (>50 degrees ), which was often concurrently managed with DTITA if intrinsic curvature was present. For SR, tubularization of the graft was performed 6 months later. RESULTS: A total of 140 patients were included. Tubularized incised plate (TIP), DIG, and SR techniques were performed in 57, 23, and 60 patients, respectively. The TIP and DIG techniques achieved similar success rates, although DIG was performed in cases of narrow and spongiosum deficient plates. Reoperation rates with TIP and DIG techniques was 52.6% and 52.1% (NS). Urethro-cutaneous fistulas were seen in 31.5% and 13% of TIP and DIG techniques, respectively. Staged repair accomplished better results than both TIP and DIG techniques, despite being performed in the most unfavorable cases (reoperation rate 28%). After technical modifications, the DIG technique achieved similar outcomes of SR. CONCLUSIONS: Proximal hypospadias remains challenging, regardless of the technique utilized for its repair. Urethro-cutaneous fistulas were more commonly seen after long TIP repairs. Approximately half of the patients undergoing long TIP and DIG procedures needed re-intervention, although the percentage decreased significantly with late modifications in the DIG group. Recurrence of VC after TIP and DIG techniques seemed to be a significant and under-reported complication. Staged repairs, despite being performed for the most severe cases, resulted in overall better outcomes. PMID- 26279103 TI - Response to commentary to "27 years of experience with the comprehensive surgical management of prune belly syndrome". PMID- 26279104 TI - Transcutaneous posterior tibial nerve stimulation in pediatric overactive bladder: A preliminary report. AB - BACKGROUND: Non-neurogenic overactive bladder (OAB) is a common problem in children that may affect their quality of life. Various methods of neuromodulation have been reported to treat refractory lower urinary tract dysfunction. Since most of these techniques are invasive, they are less applicable in children. OBJECTIVE: To evaluate the efficacy of transcutaneous PTNS in treatment of OAB in children, in a randomized clinical setting. STUDY DESIGN: This study was single-blinded, prospective, sham controlled randomized trial. 40 children with non-neurogenic OAB refractory to behavioural and anticholinergic therapy were randomized either to test group or sham group. Neuromodulation was performed using two self-adhesive electrodes cephalad to medial malleolus. In test group the stimulation was given with voltage pulse intensity of 0 to 10 mA, pulse width of 200 MUs and frequency of 20 Hz. In sham group patch electrodes were applied to simulate the test group but no stimulation was given. In both groups, weekly session of 30 min was given for a period of 12 weeks. The OAB symptoms, severity of incontinence, number of voids daily (NV), average voided volume (AVV) and maximum voided volume (MVV) were evaluated before and after treatment. RESULTS: On assessment of subjective improvement of OAB symptoms, 66.66% patients reported cure and 23.81% patients reported significant improvement of symptoms in test group whereas in sham group only 6.25% patients reported significant improvement. In test group 71.42% patients reported complete improvement in incontinence whereas in sham group only 12.5% patient reported complete improvement. The AVV, MVV and NV improved significantly in test group (p <0.001) as compared to sham group (Table). DISCUSSION: The present study is unique as none of the earlier studies in children were sham controlled. It is also first PTNS study in which patch electrodes were used; therefore it is completely noninvasive. This technique provides better patient acceptability and compliance. This study proved that, there is a definite effect of PTNS as compared to placebo because when patients from sham group were treated actively, they responded well. The present study has few limitations as it has relatively short follow-up period of 12 weeks. Relapse of OAB symptoms and maintenance schedule of PTNS need to be assessed further. CONCLUSION: Transcutaneous PTNS is superior to placebo in treatment of non-neurogenic overactive bladder in children. In view of its effectiveness and acceptability we believe that transcutaneous PTNS should be part of pediatric urology armamentarium for treatment of OAB. PMID- 26279105 TI - Effect of Falls on Frequency of Atrial Fibrillation and Mortality Risk (from the REasons for Geographic And Racial Differences in Stroke Study). AB - It is unclear if patients who have atrial fibrillation (AF) have a greater fall risk compared with those in the general population and if falls increase mortality beyond that observed in AF. A total of 24,117 (mean age 65 +/- 9.3 years; 55% women; 38% black) participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study were included. AF was identified from baseline electrocardiogram data and by self-reported history. Falls were considered present if participants reported >=2 falls within the year before the baseline examination. Logistic regression was used to examine the relationship between prevalent AF and falls. Cox regression was used to examine the risk of death in those with AF and falls, separately and in combination, compared with those without either condition. A total of 2,007 participants (8.3%) had baseline AF and 1,655 (6.7%) reported falls. A higher prevalence of falls was reported in those with AF (n = 209; 10%) than those without AF (n = 1,446; 6.5%; p <0.0001). After adjustment for fall risk factors, AF was significantly associated with falls (odds ratio 1.22, 95% confidence interval [CI] 1.04 to 1.44). Compared with no history of AF or falls, the concomitant presence of AF and falls (hazard ratio [HR] 2.12, 95% CI 1.64 to 2.74) was associated with a greater risk of death than AF (HR 1.44, 95% CI 1.28 to 1.62) or falls (HR 1.61, 95% CI 1.42 to 1.82). In conclusion, patients with AF are more likely to report a history of falls in REGARDS. Additionally, participants with AF who report falls have an increased risk of death than those with either condition in isolation. PMID- 26279106 TI - Effectiveness and Safety of Anakinra for Management of Refractory Pericarditis. AB - Recurrent pericarditis is a debilitating condition that can be recalcitrant to conventional therapy with nonsteroidal anti-inflammatory agents, colchicine, and glucocorticoids. The aim of this study was to evaluate the therapeutic role of the recombinant interleukin-1 receptor antagonist anakinra in a series of adult patients with recurrent pericarditis refractory to conventional therapy. We retrospectively reviewed the medical records of 13 consecutive patients with treatment-refractory recurrent pericarditis who received anakinra for management of their disease. None of the patients had an identified systemic inflammatory rheumatic disease. The primary end points were symptom resolution and glucocorticoid discontinuation. Thirteen patients (10 women) treated with anakinra were followed for a median (range) of 16.8 months (1.3 to 24). All patients had chest pain. Total duration of symptoms before initiation of anakinra was 3 years (1.1 to 6.0). Pericardial thickening was detected by echocardiography in 9 patients (69%). All 13 patients (100%) experienced at least a partial and, most, a complete resolution of symptoms. Response to therapy was rapid, within 2 to 5 days. At last follow-up, 11 patients (84%) had successfully discontinued concomitant nonsteroidal anti-inflammatory agent, colchicine, and glucocorticoid therapy; 11 patients remained on anakinra at the end of the follow-up period. The only side effect was transient injection site reaction in 4 patients (31%). In conclusion, anakinra may be an effective alternative agent for the management of glucocorticoid-dependent recurrent pericarditis. Side effects were minor. A formal clinical trial to evaluate the usefulness of this agent should be considered. PMID- 26279107 TI - Usefulness of Left Atrial Reservoir Size and Left Ventricular Untwisting Rate for Predicting Outcome in Primary Mitral Regurgitation. AB - The present study proposed to evaluate whether analysis of cardiac mechanics through speckle-tracking imaging is useful for risk stratification in asymptomatic patients with chronic primary mitral regurgitation (MR). We prospectively enrolled 67 patients (mean age 57 +/- 18 years) and followed them over time. MR was mild in 20 patients (30%), moderate in 24 (36%), and severe in 23 (34%). After a mean time of 24.8 +/- 17 months, 34 patients (51%) remained asymptomatic, whereas 33 (49%) developed events (19 underwent mitral valve surgery, 9 required hospitalization for acute heart failure, and 5 patients died). Compared to asymptomatic patients, those with events at baseline showed more severe MR, larger and spherical ventricles, diastolic dysfunction, and greater systolic pulmonary arterial pressure. Moreover, patients with events had decreased left atrial (LA) reservoir (p <0.001) and left ventricular (LV) untwisting rate (p <0.001). On univariate Cox regression analysis, effective regurgitant orifice area (p <0.001), vena contracta (p <0.001), systolic pulmonary arterial pressure (p = 0.003), LV end-systolic diameter (p <0.001), E/E' ratio (p = 0.004), LA volume (p = 0.001), LA reservoir (p <0.001), and LV untwisting rate (p <0.001) were associated with an increased risk of events. On multivariate analysis, only LA reservoir (p = 0.013) and LV untwisting rate were independent predictors (p = 0.017) of outcome. Moreover, LA reservoir evaluation significantly improved (p = 0.013) risk stratification compared to recommended parameters. In conclusion, impaired cardiac mechanics is more closely associated than severity of MR with the occurrence of events in asymptomatic chronic primary MR. PMID- 26279108 TI - Outpatient Use of Focused Cardiac Ultrasound to Assess the Inferior Vena Cava in Patients With Heart Failure. AB - Accurate assessment of volume status is critical in the management of patients with heart failure (HF). We studied the utility of a pocket-sized ultrasound device in an outpatient cardiology clinic as a tool to guide volume assessment. Inferior vena cava (IVC) size and collapsibility were assessed in 95 patients by residents briefly trained in focused cardiac ultrasound (FCU). Cardiologist assessment of volume status and changes in diuretic medication were also recorded. Patients were followed for occurrence of 30-day events. There was a 94% success rate of obtaining IVC size and collapsibility, and agreement between visual and calculated IVC parameters was excellent. Most patients were euvolemic by both FCU IVC and clinical bedside assessment (51%) and had no change in diuretic dose. Thirty-two percent had discrepant FCU IVC and clinical volume assessments. In clinically hypervolemic patients, the FCU evaluation of the IVC suggested that the wrong diuretic management plan might have been made 46% of the time. At 30 days, 14 events occurred. The incidence of events increased significantly with FCU IVC imaging categorization, from 11% to 23% to 36% in patients with normal, intermediate, and plethoric IVCs. By comparison, when grouped in a binary manner, there was no significant difference in event rates for patients who were deemed to be clinically volume overloaded. Assessment of volume status in an outpatient cardiology clinic using FCU imaging of the IVC is feasible in a high percentage of patients. A group of patients were identified with volume status discordant between FCU IVC and routine clinic assessment, suggesting that IVC parameters may provide a valuable supplement to the in-office physical examination. PMID- 26279109 TI - Nationwide Trends in Reported Incidence of Takotsubo Cardiomyopathy from 2006 to 2012. AB - Takotsubo cardiomyopathy (TC) is believed to be an increasingly diagnosed syndrome; however, data on its incidence are limited. The purpose of this study was to determine the reported incidence of TC in the United States and to examine its trend over several years. Data was obtained from the Nationwide Inpatient Sample, created by the Agency for Healthcare Research and Quality, for each of the years from 2006 to 2012. Hospital discharges with principal diagnosis of TC, identified using Internal Classification of Diseases, Ninth Revision, code 429.83, were included. We tabulated estimated total numbers of discharges, incidence per 100,000 persons, mean length of stay, inhospital death rates, and diagnoses stratified by age group and gender. The reported incidence of TC based on principal diagnosis at hospital discharge increased significantly over the study period, with 315 cases +/- 43 (standard error) in 2006 and 6,230 cases +/- 232 (standard error) in 2012 (p <0.001 for trend). Mean length of hospital stay was stable over the study period (3.4 days in 2006 vs 3.6 days in 2012; p = 0.74 for trend). The diagnosis was most frequent in patients aged 65 to 84 years (50% of all diagnoses in 2012), followed by those aged 45 to 64 years (39% of all diagnoses in 2012). Women accounted for >90% of diagnoses throughout the study period. In conclusion, the reported incidence of TC has increased significantly from 2006 to 2012, most likely because of increasing recognition of the syndrome. PMID- 26279110 TI - Prevalence and Implications of Subclinical Coronary Artery Disease in Patients With Atrial Fibrillation. AB - The objective of this study was to examine prevalence and clinical implications of subclinical coronary artery disease (CAD) detected by coronary artery calcium score (CACS) testing in patients with atrial fibrillation (AF). CACS was assessed in patients without history of CAD undergoing catheter ablation of AF. Age- and gender-matched patients with normal sinus rhythm (NSR) presenting with chest pain served as controls. Predicted arterial age using the Multi-Ethnic Study of Atherosclerosis registry was also compared to the chronologic age. A total of 860 patients (430 AF and 430 NSR, age 63 +/- 10 years, 65% men) were included. Subclinical CAD prevalence (CACS >0) was 74% (319 of 430) in the AF group. Compared to the patients with NSR, patients with AF had higher prevalence of Subclinical CAD (74% vs 63%; p <0.001). In multivariate analysis, AF was independently associated with Subclinical CAD (hazard ratio 1.60; p = 0.002) but only with persistent AF (hazard ratio 2.28; p <0.001). Predicted arterial age was greater than chronologic age in patients with AF (69 +/- 12 vs 64 +/- 9 years). CACS-diagnosed subclinical CAD identified new potential candidates for statin therapy (12%; 33 of 267) and for oral anticoagulation (19%; 40 of 206) by addition of subclinical CAD to the CHA2DS2-VASc scores. In conclusion, in patients without known history of CAD, prevalence of subclinical CAD was significantly higher in those with persistent AF than those with NSR. AF was associated with subclinical CAD independently and complimentarily to clinical risk factors. Identifying subclinical CAD has potential clinical indications for prevention of CAD progression and stroke. PMID- 26279111 TI - Levothyroxine Treatment of Euthyroid Children with Autoimmune Hashimoto Thyroiditis: Results of a Multicenter, Randomized, Controlled Trial. AB - BACKGROUND: Levothyroxine (L-T4) treatment of euthyroid children with Hashimoto thyroiditis (HT) is a controversial issue. PATIENTS AND METHODS: We conducted a prospective, randomized, controlled clinical trial. Out of 79 identified euthyroid patients, 59 started the study; 25 patients (21 female, 4 male; age: 11.8 +/- 2.3 years) received L-T4 at a mean dose of 1.6 ug/kg (SD, 0.8) daily, and 34 (27 female, 7 male; age: 12.6 +/- 1.2 years) were not treated. Patients developing subclinical hypothyroidism during follow-up (n = 13) were treated with L-T4 and removed from the observation group. As the main outcome measures, thyroid gland volume (determined by ultrasound) as well as serum levels of TSH, free T4, and antibodies against thyroid peroxidase and thyroglobulin were assessed every 6 months for 36 months. RESULTS: At the start, the mean thyroid volume (standard deviation score, SDS) was 2.5 in the treatment group and 1.6 in the observation group. There was a constant decline in mean thyroid volume (SDS) from 2.13 (month 12) to 1.12 (month 30) in the treated group, with a delta thyroid volume of -1.01 SDS. In the observation group, the mean delta thyroid volume increased to +0.27 SDS. The change of the delta thyroid volume was statistically significantly different between both groups during the 12- and 30 month time points (p < 0.05). L-T4 had no effect on thyroid function and serum thyroid antibodies. CONCLUSIONS: L-T4 treatment can decrease the thyroid volume in euthyroid children with HT, but the effect is limited to a definite time period. PMID- 26279112 TI - ERP evidence for hemispheric asymmetries in exemplar-specific explicit memory access. AB - The right cerebral hemisphere (RH) appears to be more effective in representing visual objects as distinct exemplars than the left hemisphere (LH) which is presumably biased towards coding objects at the level of abstract prototypes. As of yet, relatively little is known about the role that asymmetries in exemplar specificity play at the level of explicit memory retrieval. In the present study, we addressed this issue by examining hemispheric asymmetries in the putative event-related potential (ERP) correlates of familiarity (FN400) and recollection (LPC). In an incidental study phase, pictures of familiar objects were presented centrally. At test, participants performed a memory inclusion task on identical repetitions and different exemplars of study items as well as new items which were presented in only one visual hemifield using the divided visual field technique. With respect to familiarity, we observed exemplar-specific FN400 old/new effects that were more pronounced for identical repetitions than different exemplars, irrespective of the hemisphere governing initial stimulus processing. In contrast, LPC old/new effects were subject to some hemispheric asymmetries indicating that exemplar-specific recollection was more extensive in the RH than in the LH. This further corroborates the idea that hemispheric asymmetries should not be generalized but need to be distinguished not only in different domains but also at different levels of processing. PMID- 26279113 TI - Intranasal administration of human umbilical cord mesenchymal stem cells conditioned medium enhances vascular remodeling after stroke. AB - Stem cell-based treatments have been reported to be a potential strategy for stroke. However, tumorigenic potential and low survival rates of transplanted cells could attenuate the efficacy of the stem cell-based treatments. The application of stem cell-condition medium (CM) may be a practicable approach to conquer these limitations. In this study, we investigated whether intranasal administration of human umbilical cord mesenchymal stem cells (hUCMSCs)-CM has the therapeutic effects in rats after stroke. Adult male rats were subjected to middle cerebral artery occlusion (MCAo) and were treated by intranasal routine with or without hUCMSCs-CM (1 ml/kg/d), starting 24h after MCAo and daily for 14 days. Neurological functional tests, blood brain barrier (BBB) leakage, were measured. Angiogenesis and angiogenic factor expression were measured by immunohistochemistry, and Western blot, respectively. hUCMSCs-CM treatment of stroke by intranasal routine starting 24h after MCAo in rats significantly enhances BBB functional integrity and promotes functional outcome but does not decrease lesion volume compared to rats in DMEM/F12 medium control group and saline control group. Treatment of ischemic rats with hUCMSCs-CM by intranasal routine also significantly decreases the levels of Ang2 and increases the levels of both Ang1 and Tie2 in the ischemic brain. To take together, increased expression of Ang1 and Tie2 and decreased expression of Ang2, induced by hUCMSCs CM treatment, contribute to vascular remodeling in the ischemic brain which plays an important role in functional outcome after stroke. PMID- 26279114 TI - Framingham risk score can predict cognitive decline progression in Alzheimer's disease. AB - The role of vascular factors in influencing cognitive decline has been extensively investigated, and some difficulties in defining their weight in dementia pathogenesis have emerged. The aim of the study was to investigate the relevance of the Framingham cardiovascular risk profile (FCRP) in influencing cognitive deterioration in a population of Alzheimer's disease (AD) patients. Two hundred eighty-four consecutive AD patients were enrolled. For each patient, FCRP score was calculated. We did a 1-year follow-up to quantify the cognitive decline by recording changes in the Clinical Dementia Rating score. The FCRP score predicted cognitive deterioration with an area under the curve of 0.63 (95% confidence interval: 0.57-0.69; p < 0.0001). In the subpopulation of patients with a genetic increased predisposition to develop cognitive deterioration and with an advanced vascular impairment, the FCRP predictive value significantly increased with an area under the curve of 0.77 (95% confidence interval: 0.52 0.93; p < 0.05). Our findings show that FCRP can predict the progression of deterioration in AD patients. This was particularly evident in patients with major genetic and atherosclerotic risk factors. PMID- 26279116 TI - Attempts on producing lymphoid cell line from Penaeus monodon by induction with SV40-T and 12S EIA oncogenes. AB - In an attempt of in vitro transformation, transfection mediated expression of Simian virus-40 (T) antigen (SV40-T) and transduction mediated expression of Adenovirus type 12 early region 1A (12S E1A) oncogene were performed in Penaeus monodon lymphoid cells. pSV3-neo vector encoding SV40-T oncogene and a recombinant baculovirus BacP2-12S E1A-GFP encoding 12S E1A oncogene under the control of hybrid promoters were used. Electroporation and lipofection mediated transformation of SV40-T in lymphoid cells confirmed the transgene expression by phenotypic variation and the expression of GFP in co-transfection experiment. The cells transfected by lipofection (>= 5%) survived for 14 days with lower toxicity (30%), whilst on electroporation, most of the cells succumbed to death (60%) and survived cells lived up to 7 days. Transduction efficiency in primary lymphoid cells was more than 80% within 14 days of post-transduction, however, an incubation period of 7 days post-transduction was observed without detectable expression of 12S E1A. High level of oncogenic 12S E1A expression were observed after 14 day post-transduction and the proliferating cells survived for more than 90 days with GFP expression, however, without in vitro transformation and immortalization. The study put forth the requirement of transduction mediated 'specific' oncogene expression along with telomerase activation and epigenetic induction for the immortalization and establishment of shrimp cell line. PMID- 26279115 TI - Trajectories of peripheral interleukin-6, structure of the hippocampus, and cognitive impairment over 14 years in older adults. AB - We aimed to investigate if trajectory components (baseline level, slope, and variability) of peripheral interleukin-6 (IL-6) over time were related to cognitive impairment and smaller hippocampal volume and if hippocampal volume explained the associations between IL-6 and cognitive impairment. Multivariable regression models were used to test the association between IL-6 trajectory components with change in neuroimaging measures of the hippocampus and with cognitive impairment among 135 older adults (70-79 years at baseline) from the Healthy Brain Project over 14 years. IL-6 variability was positively associated with cognitive impairment (odds ratio [OR] = 5.86, 95% confidence interval [CI]: 1.24, 27.61) and with greater decrease per year of gray matter volume of the hippocampus (beta = -0.008, standard error = 0.004, p = 0.03). After adjustment for hippocampal volume, the OR of cognitive impairment decreased for each unit of IL-6 variability and CIs widened (OR = 4.36, 95% CI: 0.67, 28.29). Neither baseline levels nor slopes of IL-6 were related to cognitive impairment or hippocampal volume. We believe this has potential clinical and public health implications by suggesting adults with stable levels of peripheral IL-6 may be better targets for intervention studies for slowing or preventing cognitive decline. PMID- 26279117 TI - Nanostructured Lipid Carriers: A Novel Platform for Chemotherapeutics. AB - Cancer is a disease manifested as abnormal cells division without control. If it is not detected and cured very timely, it can invade other healthy tissues resulting in metastasis. Chemotherapy is the first line treatment for cancer, but due to lack of specificity of most of the anticancer drugs, is associated with side effects that affect the quality of life. Nanostructured lipid carriers (NLC) are one of the promising nano-carriers for the development of effective targeted therapies for cancer chemotherapeutics. These bio-compatible and/or bio degradable lipids based nanoparticles are composed of solid and liquid lipids as a core matrix dispersed in surfactant solution. NLC improve the aqueous solubility of most of the hydrophobic cancer therapeutics. Their surface modification can be used for overcoming drug resistance in cancer chemotherapy, to achieve site specific targeting for better efficacy and reduced dose related toxicity. The present review is an attempt to contemplate their pharmaceutical, biopharmaceutical aspects and application in cell targeting, gene delivery and in theranostics. PMID- 26279118 TI - Efficient Transfection of Phosphorothioate Oligodeoxyribonucleotides by lipofectamine2000 into Different Bacteria. AB - Antisense technology has been a promising strategy for combating infectious diseases caused by multi-drug resistant bacterial strains, but the poor cellular uptake and transfection efficiency of these "antisense antibiotics" is strangling the development of antisense RNA therapeutics. This study was aimed at evaluating the cellular uptake characteristics and transfection efficiency of antisense phosphorothioate oligodeoxyribonucleotides (PS-ODN) in bacterial cells mediated by LipofectamineTM 2000 (LF2000). The size and surface morphology of LF2000/ODN nanoparticle were determined by dynamic light scattering and transmission electron microscope. Then the characteristics of cellular uptake were studied by flow cytometry analysis, and antibacterial efficacy of LF2000/ODN nanoparticle targeting rpoD, an RNA polymerase primary sigma70, was tested by analyzing the growth inhibition of targeted bacteria and by RT-PCR analysis of the target genes. And the results indicated that the size of the spherical nanoparticle obtained was about 120 nm with a zeta potential about -5 mV, and the encapsulation efficiency of PS-ODN was about 95%. The cellular uptake efficiencies of LF2000/ODN nanoparticle by extended-spectrum beta -lactamase producing Escherichia coli (ESBLs-E. coli) and E. coli were 40.1% and 48.5% in a time-independent manner, while 76.7% and 79.3% by meticillin-resistant Staphylococcus aureus (MRSA) and S. aureus in a time-dependent manner. Interestingly, the uptake process was not altered by the incubation temperature. After being incubated with LF2000/ODN, the growth of tested bacteria were significantly retarded and the transcription of rpoD was inhibited. Our research not only provided a basis for further studies on delivery systems for antisense antibiotics, but also highlighted a novel cellular uptake mechanism of nanoparticle. PMID- 26279119 TI - Efficient siRNA Delivery Using PEG-conjugated PAMAM Dendrimers Targeting Vascular Endothelial Growth Factor in a CoCl2-induced Neovascularization Model in Retinal Endothelial Cells. AB - BACKGROUND: Choroidal neovascularization (CNV), also known as subretinal neovascularization, causes serious damage to the central vision as it happens more commonly in macula. The most important factor involved in angiogenesis is vascular endothelial growth factor (VEGF). By an RNAi technique, VEGF gene knockdown can be used to treat CNV. PEG-conjugated poly (amidoamine) (PEGPAMAM) dendrimers as a new type of synthetic polymers are very promising to be gene delivery carriers. METHODS: To investigate siRNA delivery efficacy of PEG-PAMAM dendrimers, we prepared dendriplexes of PEG-PAMAM dendrimers with a fluorescence labelled siRNA (PEG-PAMAM/FAM siRNA) or VEGF siRNA (PEG-PAMAM/VEGF siRNA), and studied transfection and downregulation efficacy of the dendriplexes in a cobalt chloride (CoCl2)-induced neovascularization model in retinal vascular endothelial cells (RF/6A). RESULTS: Our results demonstrate that PEG-PAMAM dendrimers had significantly higher transfection efficiency to FAM siRNA than a commercial transfection reagent PEI (1.4-fold, P<0.001) measured by flow cytometry. Compared to the PEI/VEGF siRNA polyplexes, the dendriplexes of the PEG-PAMAM/VEGF siRNA more significantly downregulated VEGF gene expression (P < 0.01) at both mRNA and protein expression level. A tube formation assay also proved that the PEG PAMAM/VEGF siRNA dendriplexes more significantly inhibited vascular-like formation than PEI/VEGF siRNA did (P < 0.001) in RF/6A. CONCLUSION: This study demonstrated that G5-PEG was more efficient than PEI in facilitating siRNA delivery, downregulating VEGF expression and inhibiting vascular-like formation on RF/6A. PMID- 26279120 TI - Implementation of "Quality by Design (QbD)" Approach for the Development of 5 Fluorouracil Loaded Thermosensitive Hydrogel. AB - BACKGROUND: The purpose of this study was to investigate Quality by Design (QbD) principle for the preparation of hydrogel products to prove both practicability and utility of executing QbD concept to hydrogel based controlled release systems. Product and process understanding will help in decreasing the variability of critical material and process parameters, which give quality product output and reduce the risk. This study includes the identification of the Quality Target Product Profiles (QTPPs) and Critical Quality Attributes (CQAs) from literature or preliminary studies. METHODS: To identify and control the variability in process and material attributes, two tools of QbD was utilized, Quality Risk Management (QRM) and Experimental Design. Further, it helps to identify the effect of these attributes on CQAs. Potential risk factors were identified from fishbone diagram and screened by risk assessment and optimized by 3-level 2- factor experimental design with center points in triplicate, to analyze the precision of the target process. This optimized formulation was further characterized by gelling time, gelling temperature, rheological parameters, in-vitro biodegradation and in-vitro drug release. RESULTS: Design space was created using experimental design tool that gives the control space and working within this controlled space reduces all the failure modes below the risk level. CONCLUSION: In conclusion, QbD approach with QRM tool provides potent and effectual pyramid to enhance the quality into the hydrogel. PMID- 26279121 TI - Algorithm to design inhibitors using stereochemically mixed l,d polypeptides: Validation against HIV protease. AB - Polypeptides have potential to be designed as drugs or inhibitors against the desired targets. In polypeptides, every chiral alpha-amino acid has enantiomeric structural possibility to become l or d amino acids and can be used as design monomer. Among the various possibilities, use of stereochemistry as a design tool has potential to determine both functional specificity and metabolic stability of the designed polypeptides. The polypeptides with mixed l,d amino acids are a class of peptidomimitics, an attractive drug like molecules and also less susceptible to proteolytic activities. Therefore in this study, a three step algorithm is proposed to design the polypeptides against desired drug targets. For this, all possible configurational isomers of mixed l,d polyleucine (Ac-Leu8 NHMe) structure were randomly modeled with simulated annealing molecular dynamics and the resultant library of discrete folds were scored against HIV protease as a model target. The best scored folds of mixed l,d structures were inverse optimized for sequences in situ and the resultant sequences as inhibitors were validated for conformational integrity using molecular dynamics. This study presents and validates an algorithm to design polypeptides of mixed l,d structures as drugs/inhibitors by inverse fitting them as molecular ligands against desired target. PMID- 26279122 TI - GAPDH-silence preserves H9C2 cells from acute hypoxia and reoxygenation injury. AB - BACKGROUND: Acute hypoxia and reoxygenation injury, as a common environmental stress condition, is a basic condition of most pathophysiological processes. It has been approve that autophagy and oxidant stress could contribute to acute hypoxia and reoxygenation injury. This study is aimed to examine the effect of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) silence on cell injury with acute hypoxia and reoxygenation injury by autophagy and antioxidant stress pathway. METHODS: GAPDH expression was silenced by siRNA in H9C2 cardiomyoblasts with acute hypoxia and reoxygenation injury. Autophagy was detected by western blot for autophagy proteins and monodansylcadaverine (MDC) staining for acidic substances. Pro-apoptosis protein and flow cytometry were used to assess cell apoptosis and death and intracellular adenosine triphosphate (ATP) relative concentration was measured. Oxidant stress was assessed by measuring 2'-7' dichlorodihydrofluorescein diacetate (DCFH-DA), thiobarbituric acid reactive substances (TBARS), glutathione (GSH) and super oxide dismutase (SOD). RESULTS: In this study, GAPDH-silence enhanced autophagy in H9C2 cells with acute hypoxia and reoxygenation injury, decreased oxidant stress and increased antioxidant pathways; and reduced cell apoptosis and death. However, GAPDH-silence had no significant effect on cell energy. CONCLUSION: GAPDH pre-silence by siRNA reduces H9C2 cell death occurring via autophagy and anti-oxidative stress pathway in acute hypoxia and reoxygenation injury. This study enriches the understanding of GAPDH pathophysiology role, and provides potential new therapeutic targets for cardiac disease states characterized by oxidative stress. PMID- 26279123 TI - Estimating height from the first and second cervical vertebrae in a Spanish population. AB - One of the roles of forensic anthropology is the identification of skeletal remains and over the years many methods have been developed to obtain specific details of a corpse such as an estimation of age and height. The femur and tibia are ideal for this purpose but unfortunately they are often missing or badly fragmented. For this reason, in this present study, we used the smaller bones of the first and second cervical vertebrae, which are often better preserved than the long bones. Direct measurement of these bones has been found to be misleading, largely due to the remains of a covering of soft tissue, and to overcome this all measurements were taken from tomographic images. The aim of this study is to provide an auxiliary diagnostic method to evaluate the association of different anthropometric measurements taken with tomographic imagery of both the first cervical and second cervical vertebra with body height within a sample of the Spanish population. Measurements were taken from tomographic images taken with a dental CT of 203 healthy individuals from a Spanish population. The best correlation was obtained in the case of unknown sex using four measurements: two of the first cervical vertebra and two of the second vertebra using the following regression formula S=49.02+1.02O+1.58DO+0.49V+0.67I. All formulae provided statistically significant results and can be applied to any skeletal remains belonging to a Spanish population. PMID- 26279124 TI - Short report: Functional somatic symptoms are associated with perfectionism in adolescents. AB - OBJECTIVE: The aim of this study is to investigate the influence of perfectionism on functional somatic symptoms (FSSs) in adolescents. It was hypothesized that perfectionism predicts higher levels of FSSs cross-sectionally and longitudinally, and that anxiety and depression mediate this relationship. DESIGN: This prospective population-based study was part of the Dutch Tracking Adolescents' Individual Lives Survey (N=2230; 50.8% girls). Data from 1878 participants attending the third (T3) or fourth (T4) assessment wave were used (mean age T3: 16.2 (SD:0.7); mean age T4: 19.0 (SD:0.6)). Multiple regression and mediation analyses were performed in Mplus. MAIN OUTCOME MEASURES: FSSs, perfectionism (i.e. the feeling one has to be perfect), anxiety and depression were assessed with the Youth Self-Report at the third and fourth wave. RESULTS: Perfectionism was associated with a higher level of FSSs in adolescents, both cross-sectionally (B=0.11, 95%-CI: 0.08-0.14) and longitudinally (B=0.05, 95%-CI: 0.02-0.08). There was a small indirect effect of perfectionism on FSSs trough anxiety and depression (B=0.02, 95%-CI: 0.003-0.03, k(2)=0.02). CONCLUSION: The results suggest that perfectionism predicts the course of FSSs with a small indirect effect of perfectionism on FSSs trough anxiety and depression. Further research is needed to clarify which aspects of perfectionism are particularly responsible for this effect. PMID- 26279125 TI - The spectral relaxation dynamics and the molecular crowding effect of silver nanoclusters synthesized in the polymer scaffold. AB - We have performed a comprehensive study on the spectral relaxation dynamics of silver nanoclusters (AgNCs) synthesized in poly(methacrylic acid) (PMAA). In different polymer conformations and solvents, the spectral relaxation dynamics of PMAA-AgNCs can be globally fitted by a bi-exponential decay, the short component is about 0.2-0.3 ns, whereas the long component is in the range 1-3 ns. The spectral relaxation is associated with the energy transfer dynamics and the excitation of multiple emissive AgNCs. In this study, we have demonstrated the feasibility of using AgNCs as a fluorescent probe for fluorescence anisotropy studies. Meanwhile, the molecular crowding effects of the PMAA-AgNCs were addressed using the Triton X-100 reverse micelles. The results indicate that the fluorescence quantum yield of the AgNCs will be significantly increased under crowded conditions, which is beneficial for their usage in intracellular imaging studies. PMID- 26279126 TI - Daytime intrusive thoughts and subjective insomnia symptoms. AB - Insomnia is increasingly recognised as a 24h complaint that is associated with an increased risk of mood and anxiety disorders. However, the effects of insomnia symptoms on maladaptive daytime patterns of thinking are poorly understood. We examined the relationship between subjective insomnia symptoms, attentional control and negative thought intrusions during daytime in a large sample of undergraduates experiencing poor sleep. A total of 109 participants completed self-report measures of sleep quality, current sleepiness, anxiety and attentional control. A behavioural measure of intrusive thought required participants to control their attention during two focus periods separated by a 5min period of self-referential worry. Thought intrusions were sampled throughout the pre- and post-worry periods. Perceived insomnia severity was associated with the reduced ability to focus attention and uniquely associated with increased negative thought intrusions in the pre-worry period. These results support suggestions that acute episodes of poor sleep can dysregulate key networks involved in attentional control and emotion regulation, and that promote negative cognitive activity. PMID- 26279127 TI - Parameters of glucose and lipid metabolism at the fasted state in drug-naive first-episode patients with psychosis: Evidence for insulin resistance. AB - Diabetes and dyslipidemia are common in patients with psychosis; this association may be partly related to adverse metabolic effects of antipsychotic medications. We assessed glucose and lipid metabolism during the fasted state in drug-naive patients with psychosis. Fasting serum concentrations of total cholesterol, triglycerides, high density lipoprotein (HDL), glucose, insulin, connecting peptide (C-peptide), homeostatic model assessment index (HOMA-IR), glycated hemoglobin (HbA1C) and serum cortisol were compared between a group of 40 newly diagnosed drug-naive, first-episode patients with psychosis and a group of 40 healthy controls, matched for age, sex and BMI. Total cholesterol, triglycerides and fasting glucose levels were similar, whereas insulin and C-peptide levels were higher and HDL marginally lower in the patients' group compared to those in healthy controls. Drug-naive patients with psychosis were more insulin resistant (as assessed by the HOMA-R index) compared to healthy controls. Serum cortisol did not differ between the two groups. There is evidence that drug-naive, first episode patients with psychosis are more insulin resistant compared to healthy controls. PMID- 26279128 TI - History of sexual, emotional or physical abuse and psychiatric comorbidity in substance-dependent patients. AB - Sexual, emotional or physical abuse history is a risk factor for mental disorders in addicted patients. However, the relationship between addiction and abuse lifespan is not well known. This study aims to compare clinical and psychopathological features of addicted patients according to the experience of abuse and to the number of different types of abuse suffered. Bivariate and multivariate analyses were conducted. 512 addicted patients seeking treatment were included, 45.9% reported abuse throughout life (38.9% emotional, 22.3% physical and 13.5% sexual abuse). It was found that female gender; depressive symptoms and borderline personality disorder were independently associated with history of any abuse throughout life. As well, it was found that 14% have been suffered from all three types of abuse (sexual, emotional and physical), 34.5% from two and 55.5% from one type. Female gender and borderline personality disorder were independently associated independently with a greater number of different types of abuse. Results suggest that history of abuse is frequent among substance-dependent patients and these experiences are more prevalent in women and are associated with more psychiatric comorbidity. PMID- 26279129 TI - Asking patients about their general level of functioning: Is IT worth IT for common mental disorders? AB - Functional disability (FD) is a diagnostic criterion for the psychiatric diagnosis of many mental disorders (e.g. generalized anxiety disorder (GAD); major depressive episode (MDE)). We aimed to assess the contribution of measuring FD to diagnosing GAD and MDE using clinical (Global Assessment of Functioning, GAF) and self-reported methods (Analog scale of functioning, ASF and World Health Organization Disability Assessment Schedule WHODAS 2.0). Patients seeking professional help for mood/anxiety symptoms (N=244) were evaluated. The MINI interview was used to determine the presence of common mental disorders. Symptoms were assessed with two short checklists. Logistic and hierarchical logistic models were used to determine the diagnostic accuracy and the added diagnostic value of FD assessment in detecting GAD and MDE. For GAD, FD alone had a diagnostic accuracy of 0.79 (GAF), 0.79 (ASF) and 0.78 (WHODAS) and for MDE of 0.83, 0.84 and 0.81, respectively. Self-reported measures of FD improved the diagnostic performance of the number of symptoms (4% AUC increase) for GAD, but not for MDE. If assessed before symptom evaluation, FD can discriminate well between patients with and without GAD/MDE. When assessed together with symptoms, self-reported methods improve GAD detection rates. PMID- 26279130 TI - The VA augmentation and switching treatments for improving depression outcomes (VAST-D) study: Rationale and design considerations. AB - Because two-thirds of patients with Major Depressive Disorder do not achieve remission with their first antidepressant, we designed a trial of three "next step" strategies: switching to another antidepressant (bupropion-SR) or augmenting the current antidepressant with either another antidepressant (bupropion-SR) or with an atypical antipsychotic (aripiprazole). The study will compare 12-week remission rates and, among those who have at least a partial response, relapse rates for up to 6 months of additional treatment. We review seven key efficacy/effectiveness design decisions in this mixed "efficacy effectiveness" trial. PMID- 26279131 TI - Clinical usefulness and relevance of intermediate endpoints for cytotoxic neoadjuvant therapy. AB - Intermediate endpoints are surrogate markers of treatment efficacy assessed earlier than the true outcome of interest. Tumor response after systemic neoadjuvant therapy is considered a suitable intermediate endpoint, especially for specific breast cancer subtypes. Response can be evaluated either after only 1 cycle of treatment by clinical evaluation or at the end of the planned neoadjuvant treatment by histomorphologic examination of all surgically removed tissues from the breast and regional nodes. Although several meta-analyses showed a lower risk of death among patients who attain a pathologic complete response (pCR) compared with patients with residual tumor in breast and/or lymph nodes after neoadjuvant therapy, a statistically significant linkage between increased pCR rate by a specific treatment and improvement of survival by the same treatment has not been demonstrated yet. Therefore, formal surrogacy of pCR is not established. Moreover, the better definition of pCR is still an open issue: a large pooled analysis demonstrated that patients who attained ypT0 ypN0 (no invasive or non-invasive residual cancer in breast and nodes) experienced longer DFS (p < 0.001) compared with patients who attained ypTis ypN0 (no invasive residual in breast and nodes irrespective of residual non-invasive disease). Nevertheless, the Food and Drug Administration (FDA) recently allowed using pCR as a surrogate endpoint for accelerated approval process. Several meta-analyses demonstrated the greatest prognostic value of pCR in more aggressive breast cancer subtypes (i.e. triple-negative, HER2-positive, or high grade breast cancer). Usefulness of an earlier intermediate endpoints was prospectively demonstrated in the GeparTrio trial in which patients showing an early response achieved 4-times more frequently a pCR than those without early response. PMID- 26279132 TI - Prognostic features of breast cancer differ between women in the Democratic Republic of Congo and Belgium. AB - OBJECTIVES: Compared to European women, breast cancers in African women present at a younger age, with a higher tumor grade and are more often estrogen receptor (ER)/progesterone receptor (PR) negative. We here investigate the histopathological and immunohistochemical characteristics (ER, PR and human epidermal growth receptor 2 (HER2)) and the proportion of triple negative (Tneg) invasive breast cancers from an unselected series of patients diagnosed in Kinshasa, and compare them to a population of Caucasian women with a palpable breast cancer. MATERIALS AND METHODS: From 2010 till 2013, during the first breast cancer awareness campaign, organized in Kinshasa, 87 patients were diagnosed with invasive breast cancer. Diagnose was based on core biopsy. The control group consisted of Caucasian women (University Hospitals of Leuven, Belgium) with a palpable mass, diagnosed between 2000 till 2009, treated with surgery of which the histopathological and immunohistochemical characteristics were collected on excision specimens. Each patient in the Kinshasa group was matched based on age and tumor size to one or more patients of the Leuven database. Differences between both groups with respect to hormone receptors (ER, PR, HER2, Tneg) or grade are presented as relative risks (RR). The analysis is based on a log-binomial model accounting for clustering through matching by a random intercept for cluster. Differences between both groups with respect to hormone receptors correcting for grade is performed by the inclusion of grade as a covariate in the model. RESULTS: After adjusting for age, tumor volume and tumor grade, ER was more frequently negative (RR = 0.71, p < 0.001), with a trend in the same direction for PR (RR = 0.87, p = 0.057), and HER2 more often positive (RR = 1.60, p = 0.015) compared to the group from the University Hospitals of Leuven. There was no difference in the proportion of breast cancers being triple negative. Sub-analysis showed that the higher HER2 positive rate was only observed in older patients (>=50y: RR = 2.07, p = 0.007) whereas no difference in HER2 positive rate was found in younger patients (<50y: RR = 1.30, p = 0.358). A higher ER negative rate was observed in both age groups, however more pronounced in older patients (>=50y: RR = 0.64, p = 0.001; <50y: RR = 0.79, p = 0.018). CONCLUSION: Breast cancer in women of Kinshasa presents at younger age and is more aggressive (more frequently ER negative and HER2 positive) compared to Caucasian women and this is more pronounced in older women (>50y). Only the ER results were concordant with the results of two similar studies (comparing an African with a European group), but were different when compared to studies on African-American women with breast cancer. This information is very important considering the treatment option: as more tumors are ER negative, endocrine therapy cannot be given while chemotherapy is often too expensive. PMID- 26279133 TI - Adjuvant endocrine therapy for postmenopausal women: Type and duration. AB - Postmenopausal women with ER positive breast cancers benefit from adjuvant endocrine therapy. Most such patients should consider aromatase inhibitor therapy at some point in their treatment course as there are modest additional risk reductions over tamoxifen therapy, alone. Longer durations of therapy - beyond five years of tamoxifen - with either ongoing tamoxifen or an AI also improve cancer outcomes. Markers of risk for early recurrence are the same as those for late recurrence. Decisions regarding the optimal type and duration of therapy reflect patient preferences in light of well described side effects of tamoxifen and AI therapy, tolerability of treatment, and established clinical, pathological and genomic markers of risk. PMID- 26279134 TI - In silico epitope analysis of unique and membrane associated proteins from Mycobacterium avium subsp. paratuberculosis for immunogenicity and vaccine evaluation. AB - Mycobacterium avium subsp. paratuberculosis (MAP) is the etiologic agent of paratuberculosis disease affecting ruminants worldwide. The aim of this study was to identify potential candidate antigens and epitopes by bio and immuno informatic tools which could be later evaluated as vaccines and/or diagnosis. 110 protein sequences were selected from MAP K-10 genome database: 48 classified as putative enzymes involved in surface polysaccharide and lipopolysaccharide synthesis, as membrane associated and secreted proteins, 32 as conserved membrane proteins, and 30 as absent from other mycobacterial genomes. These 110 proteins were preliminary screened for Major Histocompatibility Complex (MHC) class II affinity and promiscuity using ProPred program. In addition, subcellular localization and host protein homology was analyzed. From these analyses, 23 MAP proteins were selected for a more accurate inmunoinformatic analysis (i.e. T cell and B cell epitopes analysis) and for homology with mycobacterial proteins. Finally, eleven MAP proteins were identified as potential candidates for further immunogenic evaluation: six proteins (MAP0228c, MAP1239c, MAP2232, MAP3080, MAP3131 and MAP3890) were identified as presenting potential T cell epitopes, while 5 selected proteins (MAP0232c, MAP1240c, MAP1738, MAP2239 and MAP3641c) harbored a large numbers of epitopes predicted to induce both cell- and antibody mediated immune responses. Moreover, immunogenicity of selected epitopes from MAP1239c were evaluated in IFN-gamma release assay. In summary, eleven M. avium subsp. paratuberculosis proteins were identified by in silico analysis and need to be further evaluated for their immunodiagnostic and vaccine potential in field and mice model. PMID- 26279135 TI - Evaluation of a portable test system for assessing endotoxin activity in raw milk. AB - The aim of the present study was to compare endotoxin activities detected in raw milk samples obtained from cattle by a commercially available portable test system (PTS) and traditional microplate limulus amebocyte lysate (LAL)-based assay, which determined activities using a kinetic turbidimetric (KT) assay. Raw milk samples were obtained from 53 and 12 dairy cattle without and with clinical mastitis, respectively. Comparison between the KT and PTS was performed by the Friedman test. The Pearson product moment correlation coefficients were calculated to evaluate associations between any two continuous variables. Linear regression model analysis was also performed to obtain the equation describing the relationship between PTS and KT assay. The endotoxin activities detected in 200- or 400-fold diluted milk samples were similar between PTS and KT assay, whereas a significant difference was observed in 100-fold diluted milk (P<0.001). The results obtained from 200- (r(2)=0.778, P<0.001) and 400-fold diluted milk samples (r(2)=0.945, P<0.001) using PTS correlated with those using KT assay. The median milk endotoxin activities in Gram-positive and Gram-negative clinical mastitis cows were 0.655 and 11,523.5 EU/ml, respectively. The results of the present study suggest that PTS as a simple and easy test to assess endotoxin activity in raw milk is efficient, simple and reproducible. PMID- 26279136 TI - Elevated serum interleukin-1beta levels and interleukin-1beta-to-interleukin-1 receptor antagonist ratio 1 week after embryo transfer are associated with ectopic pregnancy. AB - OBJECTIVE: To investigate whether interleukin-1beta (IL-1beta) and interleukin-1 receptor antagonist (IL-1RA) serum levels in the early luteal phase differ in IVF cycles that result in an ectopic pregnancy (EP) when compared with other outcomes. DESIGN: Retrospective cohort. SETTING: Not applicable. PATIENT(S): A total of 307 women whose serum samples were available, with the following IVF outcomes: 103 live births, 80 negative pregnancy tests, 52 biochemical pregnancies, 47 EPs, and 25 miscarriages. INTERVENTION(S): Serum samples were obtained on cycle days 24 and 28 (cycle day 14 = day of egg retrieval). Levels of IL-1beta and IL-1RA were determined by quantitative ELISA performed by blinded personnel. MAIN OUTCOME MEASURE(S): IL-1beta and IL-1RA levels, IL-1beta-to-IL 1RA ratio versus cycle outcome. RESULT(S): The IL-1beta levels were predictive of an EP. At cycle days 24 and 28 the mean IL-1beta levels were higher in patients with an EP (127.1 pg/mL and 166.9 pg/mL, respectively) than in women with any other IVF outcome (15.8-55.3 pg/mL and 14.8-75.5 pg/mL, respectively). At cycle day 24 the IL-1beta-to-IL-1RA ratio was 0.18 in the ectopic group versus 0.01 0.09 in the other groups. CONCLUSION(S): Elevated IL-1beta levels and IL-1beta-to IL-1RA ratio as early as 4 days before the first pregnancy test are associated with an EP. If confirmed by prospective studies, clinical application of these findings could potentially improve EP detection. PMID- 26279138 TI - Effect of a D3 receptor antagonist on context-induced reinstatement of nicotine seeking. AB - Despite the existence of several treatment options for smoking cessation, the rate of relapse after treatment is very high. We and others have proposed that targeting the dopamine D3 receptor (DRD3) may be a good strategy for treatment of nicotine dependence. In human participants, reintroduction to an environment previously associated with drug-taking may induce relapse. In animals, such phenomenon can be studied using the context-induced reinstatement paradigm. As the role of DRD3 in context-induced reinstatement of nicotine-seeking has not yet been explored, we investigated the effects of different doses of the selective DRD3 antagonist SB-277011-A on this reinstatement. Sprague-Dawley adult rats were first trained to self-administer nicotine and subsequently underwent extinction in a second context for 5-7 days. We evaluated the effect of 1, 3 or 10mg/kg of SB-277011-A administered prior to the reintroduction to the training context. We used two different designs: 1) a between-subjects design with a unique reinstatement test; and 2) a counterbalanced within-subjects design, with 4 reinstatement tests. Our findings indicate that, in the within-subjects design, the magnitude of responding induced by the context-induced reinstatement of nicotine seeking was robust during the first reinstatement test, but significantly decreased with repeated testing. SB-277011-A (10mg/kg) blocked context-induced reinstatement of nicotine-seeking at first exposure to the context (between-subjects design), but not after repeated context exposure which produced weaker reinstatement over days. Our results support a role for DRD3 mediating context-induced reinstatement of nicotine seeking, but these effects may not be sustained over time. Further studies should explore this in human participants for validation. PMID- 26279137 TI - Rapid modification of the bone microenvironment following short-term treatment with Cabozantinib in vivo. AB - INTRODUCTION: Bone metastasis remains incurable with treatment restricted to palliative care. Cabozantinib (CBZ) is targeted against multiple receptor tyrosine kinases involved in tumour pathobiology, including hepatocyte growth factor receptor (MET) and vascular endothelial growth factor receptor 2 (VEGFR 2). CBZ has demonstrated clinical activity in advanced prostate cancer with resolution of lesions visible on bone scans, implicating a potential role of the bone microenvironment as a mediator of CBZ effects. We characterised the effects of short-term administration of CBZ on bone in a range of in vivo models to determine how CBZ affects bone in the absence of tumour. METHODS: Studies were performed in a variety of in vivo models including male and female BALB/c nude mice (age 6-17-weeks). Animals received CBZ (30 mg/kg, 5* weekly) or sterile H2O control for 5 or 10 days. Effects on bone integrity (MUCT), bone cell activity (PINP, TRAP ELISA), osteoblast and osteoclast number/mm trabecular bone surface, area of epiphyseal growth plate cartilage, megakaryocyte numbers and bone marrow composition were assessed. Effects of longer-term treatment (15-day & 6-week administration) were assessed in male NOD/SCID and beige SCID mice. RESULTS: CBZ treatment had significant effects on the bone microenvironment, including reduced osteoclast and increased osteoblast numbers compared to control. Trabecular bone structure was altered after 8 administrations. A significant elongation of the epiphyseal growth plate, in particular the hypertrophic chondrocyte zone, was observed in all CBZ treated animals irrespective of administration schedule. Both male and female BALB/c nude mice had increased megakaryocyte numbers/mm(2) tissue after 10-day CBZ treatment, in addition to vascular ectasia, reduced bone marrow cellularity and extravasation of red blood cells into the extra-vascular bone marrow. All CBZ-induced effects were transient and rapidly lost following cessation of treatment. CONCLUSION: Short-term administration of CBZ induces rapid, reversible effects on the bone microenvironment in vivo highlighting a potential role in mediating treatment responses. PMID- 26279139 TI - Large cell neuroendocrine carcinoma of the lung: CT and FDG PET findings. AB - PURPOSE: To evaluate the CT and (18)fluorine FDG PET findings of large cell neuroendocrine carcinomas (LCNECs) of the lung and to evaluate whether CT and FDG PET findings can help predict the clinical outcome. MATERIAL AND METHODS: Thirty one patients (Male:Female=29:2; mean age, 69 years) who underwent surgical resection of an LCNEC of the lung were included in this retrospective study. The tumours were assessed with respect to morphologic characteristics and the maximum standardised uptake value (SUVmax) on pre-operative CT and FDG PET. For patients undergoing curative resection (n=26), disease-free survival was evaluated using the Kaplan-Meier test. The prognostic significance was assessed using a multivariate Cox proportional hazards regression analysis. RESULTS: The mean tumour diameter was 3.8 +/- 2.1cm. Eight tumours (25.8%) were located centrally in the lung, and 23 (74.2%) were located peripherally. The margins were lobulated in 29 patients (93.5%) and well defined in 20 (64.5%). The mean SUVmax was 9.0 +/ 3.8. The five-year disease-free survival rate was 46.3%. The shorter disease free survival was related to the TNM stage greater than stage I, no lobulated margin of a tumour, a SUVmax >12.9 of a tumour, a long diameter >5.6 cm of a tumour, or female gender (P=0.115, P=0.134, P=0.056, P=0.168, P=0.113, respectively). The multivariate analysis indicated that a long diameter >5.6 cm (hazard ratio, 9.265; 90% confidence interval (CI), 1.996-42.992; P=0.017), female gender (hazard ratio, 5.579; 90% CI, 1.398-22.264; P=0.041), no lobulated margin (hazard ratio, 9.955; 90% CI, 1.433-69.136; P=0.051), and SUVmax >12.9 (hazard ratio, 4.062; 90% CI, 1.235-13.368; P=0.053) were independent predictors of shorter disease-free survival. CONCLUSIONS: LCNECs of the lung more commonly occurred peripherally and exhibited well-defined and lobulated margins on CT. The mean SUVmax was consistent with malignant tumours. Female gender, a larger tumour diameter, no lobulated margin, and higher SUVmax were poor prognostic factors. PMID- 26279140 TI - Identification of critical regions within the TIR domain of IL-1 receptor type I. AB - Interleukin-1 receptor type I (IL-1RI) belongs to a superfamily of proteins characterized by an intracellular Toll/IL-1 receptor (TIR) domain. This domain harbors three conserved regions called boxes 1-3 that play crucial roles in mediating IL-1 responses. Boxes 1 and 2 are considered to be involved in binding of adapter molecules. Amino acids possibly crucial for IL-1RI signaling were predicted via homology models of the IL-1RI TIR domain based on the crystal structure of IL-1RAPL. The role of ten of these residues was investigated by site directed mutagenesis and a functional luciferase assay reflecting NF-kappaB activity in transiently transfected Jurkat cells. In particular, the mutants E437K/D438K, E472A/E473A and S465A/S470A/S471A/E472A/E473A showed decreased and the mutant E437A/D438A increased IL-1 responsiveness compared to the mouse IL-1RI wild type. In conclusion, the alphaC' helix (Q469-E473 in mouse IL-1RI) is probably involved in heterotypic interactions of IL-1RI with IL-1RAcP or MyD88. PMID- 26279141 TI - The influence of porosity on the hemocompatibility of polyhedral oligomeric silsesquioxane poly (caprolactone-urea) urethane. AB - BACKGROUND: The physio-chemical properties of blood contacting biomaterials play an important role in determining their hemocompatibility. It is shown in literature that surface roughness and porosity have significant effect on hemocompatibility. In this study, we use a biocompatible, low thrombogenic nanocomposite polymer called POSS-PCU to test this hypothesis: would porosity compromise the hemocompatibility of POSS-PCU. We compared the hemocompatibility of POSS-PCU films of various pore sizes with PTFE, which is a commercially available material used in most blood contacting devices. METHODS: Sterilized POSS-PCU films with different size pores were prepared as samples and porous PTFE film were selected as control. And all samples were subjected to SEM for topograpgy, mechanical test for characterization and hemocompatibility tests to evaluate contact activation, platelet adhesion and activation, as well as whole blood clotting response to the samples. RESULTS: WCA significantly increased with the pore size of POSS-PCU film, whereas both tensile stress and strain decreased significantly as the sizes of pores increased. However, when compared to PTFE film with same size pores, POSS-PCU films showed both higher tensile stress and strain. Pore size had little impact over POSS-PCU's surface chemistry groups as tested by FTIR analysis. Contact activation and platelet adhesion essay also showed no significant difference between different POSS-PCU samples. However, in whole blood reactions, POSS-PCU with pores size around 2-5MUm showed higher BCI than plain films and those with pores size around 35-45MUm. POSS-PCU showed lower thrombogencity and higher hemocompatibility comparing with porous PTFE on the aspects of platelet activation, adhesion and whole blood reaction. SUMMARY AND CONCLUSIONS: POSS-PCU polymer films as a biomaterial in chronic blood contacting implants show significant lower thrombogencity and higher hemocompatibility than porous PTFE film. It is desirable as a coating or covering material in small diameter stents for treating cardiovascular diseases, cerebral vascular diseases and peripheral arterial diseases. PMID- 26279142 TI - Regulation of Lactobacillus plantarum contamination on the carbohydrate and energy related metabolisms of Saccharomyces cerevisiae during bioethanol fermentation. AB - During the industrial bioethanol fermentation, Saccharomyces cerevisiae cells are often stressed by bacterial contaminants, especially lactic acid bacteria. Generally, lactic acid bacteria contamination can inhibit S. cerevisiae cell growth through secreting lactic acid and competing with yeast cells for micronutrients and living space. However, whether are there still any other influences of lactic acid bacteria on yeast or not? In this study, Lactobacillus plantarum ATCC 8014 was co-cultivated with S. cerevisiae S288c to mimic the L. plantarum contamination in industrial bioethanol fermentation. The contaminative L. plantarum-associated expression changes of genes involved in carbohydrate and energy related metabolisms in S. cerevisiae cells were determined by quantitative real-time polymerase chain reaction to evaluate the influence of L. plantarum on carbon source utilization and energy related metabolism in yeast cells during bioethanol fermentation. Contaminative L. plantarum influenced the expression of most of genes which are responsible for encoding key enzymes involved in glucose related metabolisms in S. cerevisiae. Specific for, contaminated L. plantarum inhibited EMP pathway but promoted TCA cycle, glyoxylate cycle, HMP, glycerol synthesis pathway, and redox pathway in S. cerevisiae cells. In the presence of L. plantarum, the carbon flux in S. cerevisiae cells was redistributed from fermentation to respiratory and more reducing power was produced to deal with the excess NADH. Moreover, L. plantarum contamination might confer higher ethanol tolerance to yeast cells through promoting accumulation of glycerol. These results also highlighted our knowledge about relationship between contaminative lactic acid bacteria and S. cerevisiae during bioethanol fermentation. PMID- 26279143 TI - YB-1 gene expression is kept constant during myocyte differentiation through replacement of different transcription factors and then falls gradually under the control of neural activity. AB - We have previously reported that translation of acetylcholine receptor alpha subunit (AChR alpha) mRNA in skeletal muscle cells is regulated by Y-box binding protein 1 (YB-1) in response to neural activity, and that in the postnatal mouse developmental changes in the amount of YB-1 mRNA are similar to those of AChR alpha mRNA, which is known to be regulated by myogenic transcription factors. Here, we examined transcriptional regulation of the YB-1 gene in mouse skeletal muscle and differentiating C2C12 myocytes. Although neither YB-1 nor AChR alpha was detected at either the mRNA or protein level in adult hind limb muscle, YB-1 expression was transiently activated in response to denervation of the sciatic nerve and completely paralleled that of AChR alpha, suggesting that these genes are regulated by the same transcription factors. However, during differentiation of C2C12 cells to myotubes, the level of YB-1 remained constant even though the level of AChR alpha increased markedly. Reporter gene, gel mobility shift and ChIP assays revealed that in the initial stage of myocyte differentiation, transcription of the YB-1 gene was regulated by E2F1 and Sp1, and was then gradually replaced under the control of both MyoD and myogenin through an E-box sequence in the proximal region of the YB-1 gene promoter. These results suggest that transcription factors for the YB-1 gene are exchanged during skeletal muscle cell differentiation, perhaps playing a role in translational control of mRNAs by YB-1 in both myotube formation and the response of skeletal muscle tissues to neural stimulation. PMID- 26279144 TI - p27(Kip1) signaling: Transcriptional and post-translational regulation. AB - p27(Kip1) is an inhibitor of a broad spectrum of cyclin-dependent kinases (CDKs), and the loss of a single p27(Kip1) allele is thereby sufficient to increase tumor incidence via CDK-mediated cell cycle entry. As such, down-regulation of p27(Kip1) protein levels, in particular nuclear expressed p27(Kip1), is implicated in both disease progression and poor prognosis in a variety of cancers. p27(Kip1) expression is positively regulated by the transcription factor MENIN, and inhibited by oncogenic transcription factors MYC and PIM. However, regulation of p27(Kip1) protein expression and function is predominantly through post-translational modifications that alter both the cellular localization and the extent of E3 ubiquitin ligase-mediated degradation. Phosphorylation of p27(Kip1) at Thr(187) and Ser(10) is a prerequisite for its degradation via the E3 ubiquitin ligases SKP2 (nuclear) and KPC (cytoplasmic), respectively. Additionally, Ser(10) phosphorylated p27(Kip1) is predominantly localized in the cytoplasm due to the nuclear export protein CRM1. Another E3 ubiquitin ligase, PIRH2, degrades p27(Kip1) in both the cytoplasm and nucleus independent of phosphorylation state. As such, inhibition of cell cycle entry and progression in a variety of cancers may be achieved with therapies designed to correct p27(Kip1) localization and/or block its degradation. PMID- 26279145 TI - Tracheostomy in neurologically compromised paediatric patients: role of starplasty. AB - OBJECTIVES: Starplasty tracheostomy is an alternative to traditional tracheostomy. This paper reviews neurologically compromised paediatric patients with tracheostomies and discusses the role of starplasty tracheostomy. METHOD: A retrospective review was conducted of paediatric patients with a neurological disorder who underwent tracheostomy between 1997 and 2011. RESULTS: Forty-eight patients, with an average age of 7.3 years, were identified. The most common indications for tracheostomy were: ventilator dependence (39.6 per cent), an inability to tolerate secretions or recurrent aspiration pneumonia (33.3 per cent), and upper respiratory obstruction or hypotonia (12.5 per cent). The most common underlying neurological diagnosis was cerebral palsy. There were no early complications. Eighteen (43 per cent) of 42 patients with follow up experienced at least 1 delayed complication. Only 12 patients (28.6 per cent) were decannulated. CONCLUSION: Patients with primary neurological diagnoses have low rates of decannulation; starplasty tracheostomy should be considered for these patients. Patients with seizure disorder or acute neurological injury tended to have a higher short-term decannulation rate; traditional tracheostomy is recommended in these patients. PMID- 26279146 TI - Fertility preservation in young cancer patients--too little, too late? AB - Fertility is an important concern for many younger women with cancer; however, evidence suggests that these matters are often inadequately addressed, potentially with long-term implications for quality of life. Increased confidence in discussing fertility-related matters and an emphasis on early discussion and referral are needed to improve current practice. Further work is needed to better assess current practice and to explore how barriers to discussion about fertility preservation may be best overcome. PMID- 26279147 TI - Taxane-induced peripheral sensorial neuropathy in cancer patients is associated with duration of diabetes mellitus: a single-center retrospective study. AB - PURPOSE: The purpose of this study was to determine whether the presence of diabetes mellitus (DM) influences the incidence and severity of peripheral sensory neuropathy (PSN) in patients using taxane therapy. METHODS: A retrospective single-center analysis was conducted: Patients with PSN at baseline were excluded. The incidence of PSN was evaluated retrospectively in patient subgroups who received taxane arm and taxane-plus-platinum-agents combination arm with or without known DM at baseline. RESULTS: Three hundred seventy-four patients were enrolled in this study, 81 (21.6%) of patients had DM at baseline. The incidence of grade 1 PSN (non-DM/DM) in patients receiving taxane-based chemotherapy was 33.4/25.9% and more than grade 2 PSN (non-DM/DM) was 15/34.6%. The rate of neuropathy of non-diabetic patients was 48.8%, while the rate of diabetic patients was 52.8 and 75% in DM duration below 5 years and above 5 years group, respectively. CONCLUSIONS: This retrospective analysis indicates that taxane-based therapy in DM patients whose disease duration is above 5 years appears to affect the incidence and severity of PSN without known baseline neuropathy. The probability of PSN with taxane-based therapy was similar in DM duration below 5 years and non-DM patients. PMID- 26279148 TI - Venous access: the patient experience. AB - INTRODUCTION: The evolution of venous access via peripheral cannulation, particularly in relation to the risks and the benefits of this procedure, is reported widely in the literature. However, there is limited research specific to the patient experience of undergoing venous access. AIM: The intent of this qualitative study was to understand patients' experience of venous access, with the aim of bringing forth their voices about the experiences of repeated venous access/cannulation attempts. METHODOLOGY: This qualitative study used a hermeneutic phenomenological approach to explore the experiences of 15 participants in two rural oncology units in Australia. The participants had experienced repeated peripheral cannulation in order to receive chemotherapy. Study participants were asked to describe what it was like for them to be repeatedly cannulated. Data were collected via audiotaped individual interviews, the participants' stories were transcribed and analysed thematically. OUTCOMES: Themes emerged from the participants' stories that provided insights into their perceptions of the experience of being cannulated and the decision-making processes regarding how and where the procedure occurred. The findings suggest that a holistic approach to care was often missing causing the participants to feel vulnerable. Gaining insight into their experiences led to a greater understanding of the impact of this procedure on patients and the need to improve care through encouraging more collaborative decision-making processes between clinicians and patients. CONCLUSION: The implications for policy and practice focus on improving patient outcomes via procedural governance and education, with the intent of translating the findings from this research into evidence-based practice. PMID- 26279149 TI - Supercoiling transformation of chemical gels. AB - The swelling/deswelling behavior of chemical gels has been an unsolved problem disputed over for a long time. The Obukhov-Rubinstein-Colby model depicts the influence that swelling/deswelling has on elasticity, but its physical picture is too complicated to be sufficiently validated by experiment. In this study, we use molecular dynamics simulation to verify the validity of the molecular picture of network strands predicted by the Obukhov-Rubinstein-Colby model. We conclude that the physical picture of the Obukhov-Rubinstein-Colby model is reasonable, and furthermore the simulation can reveal the details of conformational changes in network strands during the supercoiling transformation. Our findings not only reveal the validity, but also give a better understanding of the dynamics of the swelling/deswelling behavior of chemical gels. PMID- 26279150 TI - Steering liquid metal flow in microchannels using low voltages. AB - Liquid metals based on gallium, such as eutectic gallium indium (EGaIn) and Galinstan, have been integrated as static components in microfluidic systems for a wide range of applications including soft electrodes, pumps, and stretchable electronics. However, there is also a possibility to continuously pump liquid metal into microchannels to create shape reconfigurable metallic structures. Enabling this concept necessitates a simple method to control dynamically the path the metal takes through branched microchannels with multiple outlets. This paper demonstrates a novel method for controlling the directional flow of EGaIn liquid metal in complex microfluidic networks by simply applying a low voltage to the metal. According to the polarity of the voltage applied between the inlet and an outlet, two distinct mechanisms can occur. The voltage can lower the interfacial tension of the metal via electrocapillarity to facilitate the flow of the metal towards outlets containing counter electrodes. Alternatively, the voltage can drive surface oxidation of the metal to form a mechanical impediment that redirects the movement of the metal towards alternative pathways. Thus, the method can be employed like a 'valve' to direct the pathway chosen by the metal without mechanical moving parts. The paper elucidates the operating mechanisms of this valving system and demonstrates proof-of-concept control over the flow of liquid metal towards single or multiple directions simultaneously. This method provides a simple route to direct the flow of liquid metal for applications in microfluidics, optics, electronics, and microelectromechanical systems. PMID- 26279151 TI - Redox cycling-amplified enzymatic Ag deposition and its application in the highly sensitive detection of creatine kinase-MB. AB - This communication reports a novel enzymatic Ag-deposition scheme combined with chemical-chemical redox cycling by reduced beta-nicotinamide adenine dinucleotide. This novel scheme allows a higher Ag-deposition rate than a scheme using only enzymatic Ag deposition. Therefore, it can be applied for the highly sensitive detection of a cardiac biomarker, creatine kinase-MB. PMID- 26279152 TI - Current Topics of Strategy of NSAID-Induced Small Intestinal Lesions. AB - Small intestinal mucosal injuries have been recently recognized as common complications associated with non-steroidal anti-inflammatory drugs (NSAIDs) because video capsule endoscopy and balloon enteroscopy are now available for the detection of small intestinal lesions. Small intestinal injury occurs not in an acid-dependent mechanism but by various factors such as enteric bacteria, bile acids, prostaglandin (PG) deficiency and topical factors (abnormal intestinal mucosal permeability, mitochondrial dysfunction, reactive oxygen species, endoplasmic reticulum stress and so on), and there is no well-established prophylactic approach. Several experimental and clinical studies found the effectiveness of some of the mucoprotective drugs, PG analogs, but not that of acid suppressants. Considering the effect of proton pump inhibitors (PPIs) for upper gastrointestinal (GI) disease and in the small intestine, the following 2 kinds of strategies against NSAID-induced GI injuries may be recommended. In patients with a high risk of upper GI disease (peptic ulcer etc.), simultaneous administration of a PPI (for upper GI disease) and a mucoprotective drug (for small intestine) is needed to prevent NSAID-induced GI injury. In other cases, an effective mucoprotective drug is enough for the protection of the entire digestive tract, that is, starting from the esophagus to the small intestine. These strategies may fulfill both economical and curative effects. PMID- 26279153 TI - Retrospective analysis for treatment of naive canine multicentric lymphoma with a 15-week, maintenance-free CHOP protocol. AB - Standard of care treatment of dogs with multicentric lymphoma includes combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP); however, owners may be hesitant to commit the resources necessary to complete a lengthy, multi-drug protocol. One hundred thirty-four client-owned dogs with multicentric lymphoma were treated with a 15-week CHOP chemotherapy protocol. The overall response rate was 98% with 104 dogs experiencing a complete response (CR). The median progression-free survival (PFS) time for all dogs was 176 days, and the median disease-specific overall survival time was 311 days. Prognostic factors identified on multivariate analysis as significant for PFS included substage, immunophenotype, hospitalization for adverse events, need for dose reduction, presence of neutrophilia at diagnosis, presence of anemia and experiencing a CR as best response to therapy. In conclusion, this protocol may be a viable alternative to CHOP protocols using a larger number of treatments. PMID- 26279154 TI - Designing a stepped wedge trial: three main designs, carry-over effects and randomisation approaches. AB - BACKGROUND: There is limited guidance on the design of stepped wedge cluster randomised trials. Current methodological literature focuses mainly on trials with cross-sectional data collection at discrete times, yet many recent stepped wedge trials do not follow this design. In this article, we present a typology to characterise the full range of stepped wedge designs, and offer guidance on several other design aspects. METHODS: We developed a framework to define and report the key characteristics of a stepped wedge trial, including cluster allocation and individual participation. We also considered the relative strengths and weaknesses of trials according to this framework. We classified recently published stepped wedge trials using this framework and identified illustrative case studies. We identified key design choices and developed guidance for each. RESULTS: We identified three main stepped wedge designs: those with a closed cohort, an open cohort, and a continuous recruitment short exposure design. In the first two designs, many individuals experience both control and intervention conditions. In the final design, individuals are recruited in continuous time as they become eligible and experience either the control or intervention condition, but not both, and then provide an outcome measurement at follow-up. While most stepped wedge trials use simple randomisation, stratification and restricted randomisation are often feasible and may be useful. Some recent studies collect outcome information from individuals exposed a long time before or after the rollout period, but this contributes little to the primary analysis. Incomplete designs should be considered when the intervention cannot be implemented quickly. Carry-over effects can arise in stepped wedge trials with closed and open cohorts. CONCLUSIONS: Stepped wedge trial designs should be reported more clearly. Researchers should consider the use of stratified and/or restricted randomisation. Trials should generally not commit resources to collect outcome data from individuals exposed a long time before or after the rollout period. Though substantial carry-over effects are uncommon in stepped wedge trials, researchers should consider their possibility before conducting a trial with closed or open cohorts. PMID- 26279155 TI - Landmark studies on the glucagon subfamily of GPCRs: from small molecule modulators to a crystal structure. AB - The glucagon subfamily of class B G protein-coupled receptors (GPCRs) has been proposed to be a crucial drug target for the tretmaent of type 2 diabetes. The challenges associated with determining the crystal structures of class B GPCRs relate to their large amino termini and the lack of available small molecule ligands to stabilize the receptor proteins. Following our discovery of non peptidic agonists for glucagon-like peptide-1 receptor (GLP-1R) that have therapeutic effects, we initiated collaborative efforts in structural biology and recently solved the three-dimensional (3D) structure of the human glucagon receptor (GCGR) 7-transmembrane domain, providing in-depth information about the underlying signaling mechanisms. In this review, some key milestones in this endeavor are highlighted, including discoveries of small molecule ligands, their roles in receptor crystallization, conformational changes in transmembrane domains (TMDs) upon activation and structure-activity relationship analyses. PMID- 26279156 TI - Policresulen, a novel NS2B/NS3 protease inhibitor, effectively inhibits the replication of DENV2 virus in BHK-21 cells. AB - AIM: Dengue is a severe epidemic disease caused by dengue virus (DENV) infection, for which no effective treatment is available. The protease complex, consisting of nonstructural protein 3 (NS3) and its cofactor NS2B, plays a pivotal role in the replication of DENV, thus may be a potential target for anti-DENV drugs. Here, we report a novel inhibitor of DENV2 NS2B/NS3 protease and its antiviral action. METHODS: An enzymatic inhibition assay was used for screening DENV2 NS2B/NS3 inhibitors. Cytotoxicity to BHK-21 cells was assessed with MTT assay. Antiviral activity was evaluated in BHK-21 cells transfected with Rlu-DENV-Rep. The molecular mechanisms of the antiviral action was analyzed using surface plasmon resonance, ultraviolet-visible spectral analysis and differential scanning calorimetry assays, as well as molecular docking analysis combined with site-directed mutagenesis. RESULTS: In our in-house library of old drugs (~1000 compounds), a topical hemostatic and antiseptic 2-hydroxy-3,5-bis[(4-hydroxy-2 methyl-5-sulfophenyl)methyl]-4-methyl-benzene-sulfonic acid (policresulen) was found to be a potent inhibitor of DENV2 NS2B/NS3 protease with IC50 of 0.48 MUg/mL. Furthermore, policresulen inhibited DENV2 replication in BHK-21 cells with IC50 of 4.99 MUg/mL, whereas its IC50 for cytotoxicity to BHK-21 cells was 459.45 MUg/mL. Policresulen acted as a competitive inhibitor of the protease, and slightly affected the protease stability. Using biophysical technology-based assays and molecular docking analysis combined with site-directed mutagenesis, we demonstrated that the residues Gln106 and Arg133 of DENV2 NS2B/NS3 protease directly interacted with policresulen via hydrogen bonding. CONCLUSION: Policresulen is a potent inhibitor of DENV2 NS2B/NS3 protease that inhibits DENV2 replication in BHK-21 cells. The binding mode of the protease and policresulen provides useful hints for designing new type of inhibitors against the protease. PMID- 26279158 TI - Structural basis for 18-beta-glycyrrhetinic acid as a novel non-GSH analog glyoxalase I inhibitor. AB - AIM: Glyoxalase I (GLOI), a glutathione (GSH)-dependent enzyme, is overexpressed in tumor cells and related to multi-drug resistance in chemotherapy, making GLOI inhibitors as potential anti-tumor agents. But the most studied GSH analogs exhibit poor pharmacokinetic properties. The aim of this study was to discover novel non-GSH analog GLOI inhibitors and analyze their binding mechanisms. METHODS: Mouse GLOI (mGLOI) was expressed in BL21 (DE3) pLysS after induction with isopropyl-beta-D-1-thiogalactopyranoside and purified using AKTA FPLC system. An in vitro mGLOI enzyme assay was used to screen a small pool of compounds containing carboxyl groups. Crystal structure of the mGLOI-inhibitor complex was determined at 2.3 A resolution. Molecular docking study was performed using Discovery Studio 2.5 software package. RESULTS: A natural compound 18-beta glycyrrhetinic acid (GA) and its derivative carbenoxolone were identified as potent competitive non-GSH analog mGLOI inhibitors with Ki values of 0.29 MUmol/L and 0.93 MUmol/L, respectively. Four pentacyclic triterpenes (ursolic acid, oleanolic acid, betulic acid and tripterine) showed weak activities (mGLOI inhibition ratio <25% at 10 MUmol/L) and other three (maslinic acid, corosolic acid and madecassic acid) were inactive. The crystal structure of the mGLOI-GA complex showed that the carboxyl group of GA mimicked the gamma-glutamyl residue of GSH by hydrogen bonding to the glutamyl sites (residues Arg38B, Asn104B and Arg123A) in the GSH binding site of mGLOI. The extensive van der Waals interactions between GA and the surrounding residues also contributed greatly to the binding of GA and mGLOI. CONCLUSION: This work demonstrates a carboxyl group to be an important functional feature of non-GSH analog GLOI inhibitors. PMID- 26279157 TI - Physical performance and life quality in postmenopausal women supplemented with vitamin D: a two-year prospective study. AB - AIM: To investigate the effects of calcium and vitamin D supplementation on bone turnover marker levels, muscle strength and quality of life in postmenopausal Chinese women. METHODS: A total of 485 healthy postmenopausal Chinese women (63.44+/-5.04 years) were enrolled in this open-label, 2-year, prospective, community-based trial. The participants were divided into group A, B, C, which were treated with calcium (600 mg/d) alone, calcium (600 mg/d) and cholecalciferol (800 IU/d) or calcium (600 mg/d) and calcitriol (0.25 MUg/d), respectively, for 2 years. Serum levels of 25-hydroxyvitamin D, parathyroid hormone, beta-CTX and P1NP were measured, and the muscle strength and quality of life were assessed at baseline and at 12- and 24-month follow-ups. RESULTS: Four hundred and sixty one participants completed this study. Serum levels of 25 hydroxyvitamin D were significantly increased in group C, but not changed in groups A and B at 24-month follow-up. Serum levels of parathyroid hormone, bone turnover marker beta-CTX and bone formation marker P1NP were significantly decreased in group C, while serum levels of beta-CTX were increased in group A at 24-month follow-up. The participants in group C maintained the grip strength, while those in groups A and B exhibited decreased grip strength at 24-month follow-up. The quality of life for the participants in groups B and C remained consistent, but that in group A was deteriorated at 24-month follow-up. CONCLUSION: Supplementation with calcitriol and calcium modifies the bone turnover marker levels, and maintains muscle strength and quality of life in postmenopausal Chinese women, whereas supplementation with cholecalciferol and calcium prevents aging-mediated deterioration in quality of life. PMID- 26279159 TI - Ultrasound Characteristics of Symptomatic Carotid Plaques: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Ultrasound is the most commonly used imaging modality for assessing carotid artery stenosis. A number of studies have demonstrated that surface irregularities, heterogeneous echotexture and hypoechoic plaques are risk factors for acute ischemic stroke. We performed a systematic review and meta-analysis of the literature to better define the risk of stroke based on the sonographic characteristics of carotid plaques. MATERIALS AND METHODS: We performed a comprehensive search for studies reporting imaging findings of symptomatic and asymptomatic carotid plaques on ultrasound using MEDLINE and EMBASE. We included both case-control and cohort studies examining the relationship between complex plaque and acute ischemic stroke or transient ischemic attack. Complex plaque was defined as plaque that had any of the following characteristics: heterogeneous echogenicity, echolucency, neovascularization, surface irregularity, ulceration, and intraplaque motion. Meta-analyses using the random-effects model were performed for complex plaque and each of the individual complex plaque characteristics. p < 0.05 was considered statistically significant. We explored the impact of publication bias by constructing funnel plots and testing their symmetry. We conducted the meta-analysis using Comprehensive Meta-analysis version 2.2, Englewood, N.J., USA. RESULTS: A total of 1,013 articles were screened and 23 studies with 6,706 carotid plaques were included. Ultrasound plaque characteristics with a higher prevalence in individuals with symptomatic compared to asymptomatic carotid artery stenosis included plaque neovascularity (OR = 19.68, 95% CI = 3.14-123.16), complex plaque (OR = 5.12, 95% CI = 3.42 7.67), plaque ulceration (OR = 3.58, 95% CI = 1.66-7.71), plaque echolucency (OR = 3.99, 95% CI = 3.06-5.19) and intraplaque motion (OR = 1.57, 95% CI = 1.02 2.41). Variables not associated with symptom status included heterogenous echotexture (OR = 2.68, 95% CI = 0.56-12.80) and surface irregularity without ulceration (OR = 2.38, 95% CI = 0.70-8.11). No evidence of publication bias was observed based on Eggers test (p value of 0.05 for complex plaque and 0.53 for plaque echolucency). The remaining plaque features had insufficient data to assess for publication bias. CONCLUSIONS: Our meta-analysis and systematic review of the literature demonstrated that plaques with complex features, particularly those with echolucency, neovascularization, ulceration and intraplaque motion are associated with ischemic symptoms. Assessment of carotid plaque on ultrasound may provide stroke risk information beyond measurement of luminal stenosis. Thus, sonographic evaluation of carotid artery stenosis should focus on the detection of these plaque characteristics in addition to quantifying the degree of stenosis. PMID- 26279160 TI - Prenatal Stress Alters Hippocampal Neuroglia and Increases Anxiety in Childhood. AB - Prenatal stress has been associated with detrimental outcomes of pregnancy, including altered brain development leading to behavioural pathologies. The neurosteroid allopregnanolone has been implicated in mediating some of these adverse outcomes following prenatal stress due to its potent inhibitory and anxiolytic effects on the brain. The aims of the current study were to characterise key markers for brain development as well as behavioural parameters, adrenocortical responses to handling and possible neurosteroid influences towards outcomes in guinea pig offspring in childhood. Pregnant guinea pig dams were exposed to strobe light for 2 h (9-11 a.m.) on gestational days 50, 55, 60, and 65 and were left to deliver spontaneously at term and care for their litter. Behavioural testing (open-field test, object exploration test) of the offspring was performed at postnatal day 18 (with salivary cortisol and DHEA measured), and brains were collected at post-mortem on day 21. Markers of brain development myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) were assessed via immunohistochemistry, and the neurosteroid allopregnanolone and its rate-limiting enzymes 5alpha-reductase types 1 and 2 (5alphaR1/2) were measured in neonatal brains by radioimmunoassay, reverse transcriptase polymerase chain reaction (RT-PCR), and Western blot, respectively. Brain-derived neurotrophic factor protein was measured as a marker of synaptic plasticity, and GABAA receptor subunit expression was also assessed using RT-PCR. Neonates born from mothers stressed during late pregnancy showed a reduction in both MBP (p < 0.01) and GFAP (p < 0.05) expression in the CA1 region of the hippocampus at 21 days of age. Pups of prenatally stressed pregnancies also showed higher levels of anxiety and neophobic behaviours at the equivalent of childhood (p < 0.05). There were no significant changes observed in allopregnanolone levels, 5alphaR1/2 expression, or GABAA receptor subunit expression in prenatally stressed neonates compared to controls. This study shows alterations in markers of myelination and reactive astrocytes in the hippocampus of offspring exposed to prenatal stress. These changes are also observed in offspring that show increased anxiety behaviours at the equivalent of childhood, which indicates ongoing structural and functional postnatal changes after prenatal stress exposure. PMID- 26279162 TI - Critical Analyses of the Introduction of Liquid-Based Cytology in a Public Health Service of the State of Sao Paulo, Brazil. AB - OBJECTIVE: The aim of this study was to compare the performance of the current conventional Pap smear with liquid-based cytology (LBC) preparations. STUDY DESIGN: Women routinely undergoing their cytopathological and histopathological examinations at Fundacao Oncocentro de Sao Paulo (FOSP) were recruited for LBC. Conventional smears were analyzed from women from other areas of the State of Sao Paulo with similar sociodemographic characteristics. RESULTS: A total of 218,594 cases were analyzed, consisting of 206,999 conventional smears and 11,595 LBC. Among the conventional smears, 3.0% were of unsatisfactory preparation; conversely, unsatisfactory LBC preparations accounted for 0.3%. The ASC-H (atypical squamous cells - cannot exclude high-grade squamous intraepithelial lesion) frequency did not demonstrate any differences between the two methods. In contrast, the incidence of ASC-US (atypical squamous cells of undetermined significance) was almost twice as frequent between LBC and conventional smears, at 2.9 versus 1.6%, respectively. An equal percentage of high-grade squamous intraepithelial lesions were observed for the two methods, but not for low-grade squamous intraepithelial lesions, which were more significantly observed in LBC preparations than in conventional smears (2.2 vs. 0.7%). The index of positivity was importantly enhanced from 3.0% (conventional smears) to 5.7% (LBC). CONCLUSIONS: LBC performed better than conventional smears, and we are truly confident that LBC can improve public health strategies aimed at reducing cervical lesions through prevention programs. PMID- 26279163 TI - Effect of dexamethasone on the expression of atrogin-1/MAFbx in chick skeletal muscle. AB - Expression of atrogin-1/MAFbx, a muscle-specific E3 ubiquitin ligase, is high under catabolic conditions, that result in muscle atrophy. Messenger RNA (mRNA) expression of atrogin-1/MAFbx is increased by the glucocorticoid dexamethasone in mammalian skeletal muscle. This study investigated the effects of dexamethasone on expression of atrogin-1/MAFbx in skeletal muscle of neonatal chicks and in chick myotubes. Chicks were given a single intraperitoneal injection of dexamethasone at a concentration of 10 mg/kg body weight. Twenty-four hours after dexamethasone administration, the Pectoralis muscle weight of chicks was decreased. mRNA expression of atrogin-1/MAFbx in skeletal muscle of chicks was significantly increased by dexamethasone administration. Expression of other proteolytic-related genes (20S proteasome C2 subunit, m-calpain large subunit, and cathepsin B) in skeletal muscle of chicks was not increased by dexamethasone administration. Chick myotubes were incubated with dexamethasone (1, 10 or 100 umol/L) for 6 h. Expression of atrogin-1/MAFbx mRNA in chick myotubes was increased in the presence of all concentrations of dexamethasone. However, expression of other proteolytic-related genes (20S proteasome C2 subunit, m calpain large subunit and cathepsin B) in chick myotubes was not affected by dexamethasone treatment. These results indicate that dexamethasone enhances atrogin-1/MAFbx expression in chick skeletal muscle, resulting in increased muscle atrophy. PMID- 26279161 TI - Current position of TNF-alpha in melanomagenesis. AB - Melanoma is one of the most heterogeneous and immunogenic forms of cancer. Both tumor and stroma cells synthesize many cytokines involved in rapid development and metastasis. One of these cytokines from the tumor milieu is tumor necrosis factor-alpha (TNF-alpha), which seems to have an intricate role in melanomagenesis. Initially, it was found that TNF-alpha can induce apoptosis of tumor cells through both extrinsic and intrinsic pathways, in contrast with later studies that revealed its protumoral activity. TNF-alpha is involved in inflammation, inducing the secretion of survival molecules like antiapoptotic proteins, proangiogenetic factors and metastasis markers. Although there are many therapeutic strategies against melanoma, the prognosis of advanced stages remains poor, due to several tumor resistance mechanisms. TNF seems to be a negative prognostic factor in melanoma surgery and correlates with chemotherapy resistance. However, high intratumoral levels of TNF-alpha might be beneficial for immunotherapy. Researchers may redirect their studies in the future by double activating of the proinflammatory molecule TNF-alpha and the immune cells in order to obtain an antitumoral response in metastatic melanoma. PMID- 26279165 TI - Xenopus in Space and Time: Fossils, Node Calibrations, Tip-Dating, and Paleobiogeography. AB - Published data from DNA sequences, morphology of 11 extant and 15 extinct frog taxa, and stratigraphic ranges of fossils were integrated to open a window into the deep-time evolution of Xenopus. The ages and morphological characters of fossils were used as independent datasets to calibrate a chronogram. We found that DNA sequences, either alone or in combination with morphological data and fossils, tended to support a close relationship between Xenopus and Hymenochirus, although in some analyses this topology was not significantly better than the Pipa + Hymenochirus topology. Analyses that excluded DNA data found strong support for the Pipa + Hymenochirus tree. The criterion for selecting the maximum age of the calibration prior influenced the age estimates, and our age estimates of early divergences in the tree of frogs are substantially younger than those of published studies. Node-dating and tip-dating calibrations, either alone or in combination, yielded older dates for nodes than did a root calibration alone. Our estimates of divergence times indicate that overwater dispersal, rather than vicariance due to the splitting of Africa and South America, may explain the presence of Xenopus in Africa and its closest fossil relatives in South America. PMID- 26279164 TI - Potentially Inappropriate Prescribing in Disabled Older Patients with Chronic Diseases: A Screening Tool of Older Persons' Potentially Inappropriate Prescriptions versus Beers 2012 Criteria. AB - OBJECTIVE: To evaluate the prescription of potentially inappropriate medications (PIM), using the Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) and Beers criteria, to disabled older people. SUBJECTS AND METHODS: One hundred and forty-one patients aged >=65 years with Barthel scale scores <=60 and a regular intake of medication for chronic diseases at Chung Shan Medical University Hospital from July to December 2012 were included, and their medical records were reviewed. Comprehensive patient information was extracted from the patients' medical notes. The STOPP and Beers 2012 criteria were used separately to identify PIM, and logistic regression analyses were performed to identify risk factors for PIM. The optimal cutoff for the number of medications prescribed for predicting PIM was estimated using the Youden index. RESULTS: Of the 141 patients, 94 (66.7%) and 94 (66.7%) had at least one PIM identified by the STOPP and Beers criteria, respectively. In multivariate analysis, PIM identified by the Beers criteria were associated with the prescription of multiple medications (p = 0.013) and the presence of psychiatric diseases (p < 0.001), whereas PIM identified by the STOPP criteria were only associated with the prescription of multiple medications (p = 0.008). The optimal cutoff for the number of medications prescribed for predicting PIM by using the STOPP or Beers criteria was 6. After adjustment for covariates, patients prescribed >=6 medications had a significantly higher risk of PIM, identified using the STOPP or Beers criteria, compared to patients prescribed <6 medications (both p < 0.05). CONCLUSION: This study revealed a high frequency of PIM in disabled older patients with chronic diseases, particularly those prescribed >=6 medications. PMID- 26279166 TI - Net ecosystem exchange of CO2 with rapidly changing high Arctic landscapes. AB - High Arctic landscapes are expansive and changing rapidly. However, our understanding of their functional responses and potential to mitigate or enhance anthropogenic climate change is limited by few measurements. We collected eddy covariance measurements to quantify the net ecosystem exchange (NEE) of CO2 with polar semidesert and meadow wetland landscapes at the highest latitude location measured to date (82 degrees N). We coupled these rare data with ground and satellite vegetation production measurements (Normalized Difference Vegetation Index; NDVI) to evaluate the effectiveness of upscaling local to regional NEE. During the growing season, the dry polar semidesert landscape was a near-zero sink of atmospheric CO2 (NEE: -0.3 +/- 13.5 g C m(-2) ). A nearby meadow wetland accumulated over 300 times more carbon (NEE: -79.3 +/- 20.0 g C m(-2) ) than the polar semidesert landscape, and was similar to meadow wetland NEE at much more southerly latitudes. Polar semidesert NEE was most influenced by moisture, with wetter surface soils resulting in greater soil respiration and CO2 emissions. At the meadow wetland, soil heating enhanced plant growth, which in turn increased CO2 uptake. Our upscaling assessment found that polar semidesert NDVI measured on site was low (mean: 0.120-0.157) and similar to satellite measurements (mean: 0.155-0.163). However, weak plant growth resulted in poor satellite NDVI-NEE relationships and created challenges for remotely detecting changes in the cycling of carbon on the polar semidesert landscape. The meadow wetland appeared more suitable to assess plant production and NEE via remote sensing; however, high Arctic wetland extent is constrained by topography to small areas that may be difficult to resolve with large satellite pixels. We predict that until summer precipitation and humidity increases enough to offset poor soil moisture retention, climate-related changes to productivity on polar semideserts may be restricted. PMID- 26279167 TI - The Long-Term Influence of Tissue Inhibitor of Matrix Metalloproteinase-1 in Patients with Mild to Moderate Coronary Artery Lesions in a Chinese Population: A 7-Year Follow-Up Study. AB - OBJECTIVES: Matrix metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and their ratio (MMP-9/TIMP-1) are involved in multiple processes that are associated with coronary heart disease and are especially associated with cardiovascular events. However, few long-term population-based clinical studies have evaluated the role of these factors in cardiovascular events in a Chinese population. METHODS: A prospective study was performed on 560 patients with mild to moderate coronary artery lesions. MMP-9, TIMP-1 and their ratio were determined. RESULTS: A total of 522 of patients completed the follow-up. The median follow-up time was 64 months. Kaplan-Meier analysis demonstrated a clear increase of the incidence of major adverse cardiac events (MACEs) during the follow-up period in subjects with above-median levels of TIMP-1 (p = 0.033), whereas there was no association with either MMP-9 (p = 0.199) or MMP-9/TIMP-1 (p = 0.631). Multivariate Cox proportional hazards analysis showed the same results after further adjustment for covariates. Patients with above-median levels of TIMP-1 were more likely to suffer from adverse outcomes than patients with below-median levels of TIMP-1. However, the lack of relationship of MACEs with MMP-9 and MMP-9/TIMP-1 remained. CONCLUSIONS: Higher circulating TIMP-1 concentrations were associated with cardiovascular events during long-term follow-up of Chinese patients with mild to moderate coronary artery lesions. PMID- 26279169 TI - Athletic performance and recovery-stress factors in cycling: An ever changing balance. AB - We sought to examine whether the relationship between recovery-stress factors and performance would differ at the beginning (Stage 1) and the end (Final Stage) of a multi-stage cycling competition. Sixty-seven cyclists with a mean age of 21.90 years (SD = 1.60) and extensive international experience participated in the study. The cyclists responded to the Recovery-Stress Questionnaire for Athletes (RESTQ-Sport) and rated their performance (1 = extremely poor to 10 = excellent) in respect to the first and last stage. Two step-down multiple regression models were used to estimate the relationship among recovery (nine factors; e.g. Physical Recovery, Sleep Quality) and stress factors (10 factors; e.g. Lack of Energy, Physical Complaints), as assessed by the RESTQ-Sport and in relation to performance. Model 1 pertained to Stage 1, whereas Model 2 used data from the Final Stage. The final Model 1 revealed that Physical Recovery (beta = .46, p = .01), Injury (beta = -.31, p = .01) and General Well-being (beta = -.26, p = .04) predicted performance in Stage 1 (R(2) = .21). The final Model 2 revealed a different relationship between recovery-stress factors and performance. Specifically, being a climber (beta = .28, p = .01), Conflicts/Pressure (beta = .33, p = .01), and Lack of Energy (beta = -.37, p = .01) were associated with performance at the Final Stage (R(2) = .19). Collectively, these results suggest that the relationship among recovery and stress factors changes greatly over a relatively short period of time, and dynamically influences performance in multi stage competitions. PMID- 26279168 TI - Hypertension Control and Its Correlates Among Adults Attending a Hypertension Clinic in Tanzania. AB - Hypertension control rates are low in sub-Saharan Africa. Population-specific determinants of blood pressure (BP) control have not been adequately described. The authors measured BP and conducted interviews to determine factors associated with BP control among adults attending a hypertension clinic in Tanzania. Three hundred adults were enrolled. BP was controlled in 47.7% of patients at the study visit but only 28.3% over three consecutive visits. Demographic and socioeconomic factors were not associated with control. Obesity and higher medication cost were associated with decreased control. Their effect was mediated through adherence. Good knowledge of (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.0-6.1; P=.047), attitudes towards (OR, 2.7; 95% CI, 1.0-7.1; P=.04), and practices concerning (OR, 5.4; 95% CI, 2.3-13.0; P<.001) hypertension were independently associated with increased control, even after adjusting for mediation through adherence. Good adherence had the strongest association with control (OR, 14.6; 95% CI, 5.8-37.0; P<.001). Strategies to reduce hypertension-related morbidity and mortality in sub-Saharan Africa should target these factors. Interventional studies of such strategies are needed. PMID- 26279170 TI - Clinical evaluation of the efficacy and safety of fractional bipolar radiofrequency for the treatment of moderate to severe acne scars. AB - Several treatment modalities are used for the treatment of acne scars with variable results. Recent studies showed that fractional radiofrequency may be an effective treatment modality for acne scars. The objective of this study was to assess the efficacy, safety, tolerability and patient satisfaction of fractional bipolar radiofrequency (RF), the eTwoTM system (Syneron Candela Ltd., Yokneam, Israel) for treating acne scars. Twelve patients with moderate to severe acne scars received 3-5 treatments with the Sublative fractionated bipolar RF applicator of the eTwo device at 1-month intervals. Patients were evaluated clinically and photographically at each visit and 3 months after the final treatment. Very good improvement (at least one scale) was seen after completing the five treatments. The patient satisfaction survey (Global Aesthetic Improvement Scale scores) revealed that half (6 out of 12) of the patients reported to be satisfied with treatment results, while the other half reported to be very satisfied. Beyond the expected erythema and minimal scab formation in the treated areas, which was mild and transient, none of the participants reported any adverse events. The data presented here support the high efficacy and safety of fractionated bipolar RF for the aesthetic improvement of moderate to severe acne scars. PMID- 26279171 TI - Gestational Weight Gain and Offspring Longitudinal Growth in Early Life. AB - BACKGROUND: Excessive gestational weight gain (GWG) increases the risk of childhood obesity, but little is known about its association with infant growth patterns. AIM: The aim of this study was to examine the association between GWG and infant growth patterns. METHODS: Pregnant women (n = 743) self-reported GWG at delivery, which we classified as inadequate, adequate or excessive based on the current guidelines. Offspring weight-for-age z-score (WAZ), length-for-age z score (LAZ (with height-for-age (HAZ) in place of length at 36 months)) and body mass index z-score (BMIZ) were calculated at birth, 8, 18 and 36 months using the 2006 World Health Organization growth standards. Linear mixed models estimated the change in z-score from birth to 36 months by GWG. RESULTS: The mean (SD) WAZ was -0.22 (1.20) at birth. Overall, WAZ and BMIZ increased from birth to, approximately, 24 months and decreased from 24 to 36 months, while LAZ/HAZ decreased from birth through 36 months. Excessive GWG was associated with higher offspring WAZ and BMIZ at birth, 8 and 36 months, and higher HAZ at 36 months, compared with adequate GWG. Compared with the same referent, inadequate GWG was associated with smaller WAZ and BMIZ at birth and 8 months. CONCLUSION: Excessive GWG may predispose infants to obesogenic growth patterns, while inadequate GWG may not have a lasting impact on infant growth. PMID- 26279172 TI - Home-based virtual reality balance training and conventional balance training in Parkinson's disease: A randomized controlled trial. AB - BACKGROUND/PURPOSE: Virtual reality has the advantage to provide rich sensory feedbacks for training balance function. This study tested if the home-based virtual reality balance training is more effective than the conventional home balance training in improving balance, walking, and quality of life in patients with Parkinson's disease (PD). METHODS: Twenty-three patients with idiopathic PD were recruited and underwent twelve 50-minute training sessions during the 6-week training period. The experimental group (n = 11) was trained with a custom-made virtual reality balance training system, and the control group (n = 12) was trained by a licensed physical therapist. Outcomes were measured at Week 0 (pretest), Week 6 (posttest), and Week 8 (follow-up). The primary outcome was the Berg Balance Scale. The secondary outcomes included the Dynamic Gait Index, timed Up-and-Go test, Parkinson's Disease Questionnaire, and the motor score of the Unified Parkinson's Disease Rating Scale. RESULTS: The experimental and control groups were comparable at pretest. After training, both groups performed better in the Berg Balance Scale, Dynamic Gait Index, timed Up-and-Go test, and Parkinson's Disease Questionnaire at posttest and follow-up than at pretest. However, no significant differences were found between these two groups at posttest and follow-up. CONCLUSION: This study did not find any difference between the effects of the home-based virtual reality balance training and conventional home balance training. The two training options were equally effective in improving balance, walking, and quality of life among community dwelling patients with PD. PMID- 26279173 TI - Fibrosis index based on four factors better predicts advanced fibrosis or cirrhosis than aspartate aminotransferase/platelet ratio index in chronic hepatitis C patients. AB - BACKGROUND/PURPOSE: Liver biopsy is the gold standard to determine the severity of hepatic fibrosis despite its risk and invasiveness. The aspartate aminotransferase/platelet ratio index (APRI) could noninvasively predict the severity of hepatic fibrosis in chronic hepatitis C (CHC) patients. Whether fibrosis index based on four factors (FIB-4) could better predict the severity of hepatic fibrosis than APRI in CHC patients remains inconclusive. METHODS: This retrospective study enrolled 1473 CHC patients (784 men and 689 women) with liver biopsy and clinical data including age, aspartate aminotransferase, alanine aminotransferase, and platelet count. FIB-4 and APRI were calculated with a formula using the four clinical parameters. Hepatic fibrosis was staged using the Metavir classification system. RESULTS: The areas under the receiver operating characteristics of FIB-4 for the diagnosis of significant fibrosis (>= F2), advanced fibrosis (>= F3), and cirrhosis (F4) were 0.816 [95% confidence interval (CI), 0.795-0.836], 0.827 (95% CI, 0.806-0.849), and 0.849 (95% CI, 0.830-0.867), respectively, compared with those of APRI-0.799 (95% CI, 0.778-0.819), 0.791 (95% CI, 0.770-0.812), and 0.802 (95% CI, 0.781-0.922). In addition, the areas under the receiver operating characteristics of FIB-4 were significantly greater than those of APRI for patients with advanced fibrosis and cirrhosis, respectively (p < 0.0001). CONCLUSION: FIB-4 could predict hepatic fibrosis in CHC patients. By adding two parameters (age and alanine aminotransferase), FIB-4 better predicts advanced fibrosis and cirrhosis than APRI in CHC patients. PMID- 26279174 TI - Risk factors of suicide mortality among multiple attempters: A national registry study in Taiwan. AB - BACKGROUND/PURPOSE: Little is known about the risk factors of suicide mortality among multiple attempters. This study aims to investigate the predictors of suicidal mortality in a prospective cohort of attempters in Taiwan, focusing on the time interval and suicide method change between the last two nonfatal attempts. METHODS: The representative data retrieved from the National Suicide Surveillance System (NSSS) was linked with National Mortality Database to identify the causes of death in multiple attempters during 2006-2008. Cox proportional hazard models were applied to calculate the hazard ratios for the predictors of suicide. RESULTS: Among the 55,560 attempters, 6485 (11.7%) had survived attempts ranging from one to 11 times; 861 (1.5%) eventually died by suicide. Multiple attempters were characterized by female (OR = 1.56, p < 0.0001), nonrecipient of national aftercare service (OR = 1.62, p < 0.0001), and current contact with mental health services (OR = 3.17, p < 0.0001). Most multiple attempters who survived from hanging (68.1%) and gas poisoning (61.9%) chose the same method in the following fatal episode. Predictors of suicidal death were identified as male, older age (>= 45 years), shorter interval and not maintaining methods of low lethality in the last two nonfatal attempts. Receipt of nationwide aftercare was associated with lower risk of suicide but the effect was insignificant. CONCLUSION: The time interval of the last two nonfatal attempts and alteration in the lethality of suicide method were significant factors for completed suicide. Risk assessment involving these two factors may be necessary for multiple attempters in different clinical settings. Effective strategies for suicide prevention emphasizing this high risk population should be developed in the future. PMID- 26279175 TI - The Impact of the in utero and Early Postnatal Environments on Grey and White Matter Volume: A Study with Adolescent Monozygotic Twins. AB - Prenatal and early postnatal adversities have been shown to be associated with brain development. However, we do not know how much of this association is confounded by genetics, nor whether the postnatal environment can moderate the impact of in utero adversity. This study used a monozygotic (MZ) twin design to assess (1) the association between birth weight (BW) and brain volume in adolescence, (2) the association between within-twin-pair BW discordance and brain volume discordance in adolescence, and (3) whether the association between BW and brain volume in adolescence is mediated or moderated by early negative maternal parenting behaviours. These associations were assessed in a sample of 108 MZ twins followed longitudinally since birth and scanned at age 15. The total grey matter (GM) and white matter (WM) volumes were obtained using the Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra (DARTEL) toolbox in the Statistical Parametric Mapping version 8 (SPM8). We found that the BW was significantly associated with the total GM and WM volumes, particularly in the superior frontal gyrus and thalamus. Within-twin-pair discordance in BW was also significantly associated with within-pair discordance in both the GM and the WM volumes, supporting the hypothesis that the specific in utero environment is associated with brain development independently of genetics. Early maternal hostile parenting behaviours and depressive symptoms were associated with total GM volume but not WM volume. Finally, greater early maternal hostility may moderate the association between the BW and GM volume in adolescence, since the positive association between the BW and total GM volume appeared stronger at higher levels of maternal hostility (trend). Together, these findings support the importance of the in utero and early environments for brain development. PMID- 26279176 TI - Low-Dose Atypical Antipsychotic Risperidone Improves the 5-Year Outcome in Alzheimer's Disease Patients with Sleep Disturbances. AB - Sleep disturbances (SD) accelerate the progression of Alzheimer's disease (AD) and increase the stress of caregivers. However, the long-term outcome of disturbed nocturnal sleep/wake patterns in AD and on increased stress of spousal caregivers is unclear. This study assessed the 5-year effect of nocturnal SD on the long-term outcome in AD patients. A total of 156 donepezil-treated mild moderate AD patients (93 AD + SD and 63 AD - SD as a control group) were recruited. The AD + SD patients were formed into 4 subgroups according to the preferences of spousal caregivers for treatment with atypical antipsychotics (0.5 1 mg risperidone, n = 22), non-benzodiazepine hypnotic (5-10 mg zolpidem tartrate, n = 33), melatonin (2.55 mg, n = 9), or no-drug treatment (n = 29). SD were evaluated by polysomnography, sleep scale, and cognitive scale examinations. Moreover, all spousal caregivers of AD patients were assessed using a series of scales, including sleep, anxiety, mood, and treatment attitude scales. Our data showed that nocturnal sleep/wake disturbances were significantly associated with lower 5-year outcomes for AD patients, earlier nursing home placement, and more negative emotions of spousal caregivers. Treatment with low-dose atypical antipsychotic risperidone improved the 5-year outcome in AD + SD patients. In conclusion, low-dose atypical antipsychotic risperidone improves the 5-year outcome in AD patients with SD. Moreover, improvement of nocturnal sleep problems in AD patients will also bring better emotional stability for AD caregivers. PMID- 26279177 TI - An audience with...Gloria Maldonado. PMID- 26279178 TI - Well-Being Therapy in a Patient with Panic Disorder Who Failed to Respond to Paroxetine and Cognitive Behavior Therapy. PMID- 26279180 TI - Dielectric Breakdown of Single-Crystal Strontium Titanate. AB - Measurements of the intrinsic dielectric breakdown strength of single-crystal strontium titanate over a temperature range from -195 degrees to + 100 degrees C and under both pulse and dc conditions are described; dc breakdown at + 100 degrees C is thermal in origin. At room temperature and at -40 degrees C the breakdown strength is independent of duration of applied field and of sample configuration and hence may properly be termed intrinsic. At -80 degrees and 195 degrees C, both the values of breakdown strength and the scatter of the data depend strongly on sample configuration. The breakdown strength unexpectedly decreases with increasing temperature. Current-voltage curves show an anomalous saturation effect at low temperature. These effects may be qualitatively explained by postulating that the high electrostrictive stress causes the creation of electron trapping centers. PMID- 26279179 TI - The stool microbiota of insulin resistant women with recent gestational diabetes, a high risk group for type 2 diabetes. AB - The gut microbiota has been linked to metabolic diseases. However, information on the microbiome of young adults at risk for type 2 diabetes (T2D) is lacking. The aim of this cross-sectional analysis was to investigate whether insulin resistant women with previous gestational diabetes (pGDM), a high risk group for T2D, differ in their stool microbiota from women after a normoglycemic pregnancy (controls). Bacterial communities were analyzed by high-throughput 16S rRNA gene sequencing using fecal samples from 42 pGDM and 35 control subjects 3-16 months after delivery. Clinical characterization included a 5-point OGTT, anthropometrics, clinical chemistry markers and a food frequency questionnaire. Women with a Prevotellaceae-dominated intestinal microbiome were overrepresented in the pGDM group (p < 0.0001). Additionally, the relative abundance of the phylum Firmicutes was significantly lower in women pGDM (median 48.5 vs. 56.8%; p = 0.013). Taxa richness (alpha diversity) was similar between the two groups and with correction for multiple testing we observed no significant differences on lower taxonomic levels. These results suggest that distinctive features of the intestinal microbiota are already present in young adults at risk for T2D and that further investigations of a potential pathophysiological role of gut bacteria in early T2D development are warranted. PMID- 26279181 TI - Comparison of coping strategies and supports between aboriginal and non aboriginal people living with HIV in Ontario. AB - Complex historical and cultural factors have contributed to the HIV epidemic among Aboriginal populations in Canada. This study assesses social supports, adaptive and maladaptive coping mechanisms, stress, and mastery of Canadian-born Aboriginal and Canadian-born Caucasian people living with HIV in Ontario and posits that coping and social support are important micro- and meso-level factors associated with the epidemic. This cross-sectional analysis included questionnaire data collected from 2007 to 2011 at HIV clinics in Toronto. Categorical and continuous variables were compared using chi-square and Wilcoxon rank sum tests, respectively. Correlates of social support and coping were determined using univariate and multivariable linear regression. The analysis included 70 Aboriginal and 665 Caucasian participants. Aboriginal participants had lower levels of employment, education, and annual household income. Aboriginal participants reported more overall (7 vs. 4, p = 0.0003), ongoing (4 vs. 2, p = 0.0004), and early childhood (2 vs. 1, p = 0.02) stressors. Maladaptive coping, adaptive coping, and mastery scores were similar between Aboriginal and Caucasian participants. In multivariable analysis, injection drug use and lower education levels were significant correlates of higher maladaptive coping and lower overall support scores. Despite numerous socioeconomic challenges and personal stressors, Aboriginal people living with HIV who are accessing care exhibited comparable coping and mastery scores to Canadian-born Caucasian people living with HIV, suggesting remarkable strengths within Aboriginal people living with HIV and their communities. PMID- 26279182 TI - RG7112, a Small-Molecule Inhibitor of MDM2, Enhances Trabectedin Response in Soft Tissue Sarcomas. AB - MDM2 is a critical negative regulator of the p53 tumor suppressor protein. Selected sarcoma subtypes are being treated with Trabectedin in second line, which promotes DNA damage and p53-dependent apoptosis. The aim of this study was to evaluate the improvement of Trabectedin response with MDM2 inhibitors in soft tissue sarcomas. The antitumor effects of Trabectedin, Nutlin-3A and RG7112 as single agents or in combination were examined in vitro. RG7112 significantly synergized with Trabectedin in MDM2-amplified liposarcoma cells, representing a promising new therapeutic strategy for the treatment of sarcomas with MDM2 amplification. PMID- 26279183 TI - Application of Hybrid Fillers for Improving the Through-Plane Heat Transport in Graphite Nanoplatelet-Based Thermal Interface Layers. AB - The in-plane alignment of graphite nanoplatelets (GNPs) in thin thermal interface material (TIM) layers suppresses the though-plane heat transport thus limiting the performance of GNPs in the geometry normally required for thermal management applications. Here we report a disruption of the GNP in-plane alignment by addition of spherical microparticles. The degree of GNP alignment was monitored by measurement of the anisotropy of electrical conductivity which is extremely sensitive to the orientation of high aspect ratio filler particles. Scanning Electron Microscopy images of TIM layer cross-sections confirmed the suppression of the in-plane alignment. The hybrid filler formulations reported herein resulted in a synergistic enhancement of the through-plane thermal conductivity of GNP/Al2O3 and GNP/Al filled TIM layers confirming that the control of GNP alignment is an important parameter in the development of highly efficient GNP and graphene-based TIMs. PMID- 26279184 TI - Editorial: Alzheimer's Disease - Mechanisms, Drug Targets and Alternative Treatments. PMID- 26279185 TI - Transcriptomic Analysis of the Regulation of Rhizome Formation in Temperate and Tropical Lotus (Nelumbo nucifera). AB - Rhizome is the storage organ of lotus derived from modified stems. The development of rhizome is a complex process and depends on the balanced expression of the genes that is controlled by environmental and endogenous factors. However, little is known about the mechanism that regulates rhizome girth enlargement. In this study, using RNA-seq, transcriptomic analyses were performed at three rhizome developmental stages-the stolon, middle swelling and later swelling stage -in the cultivars 'ZO' (temperate lotus with enlarged rhizome) and 'RL' (tropical lotus with stolon). About 348 million high-quality reads were generated, and 88.5% of the data were mapped to the reference genome. Of 26783 genes identified, 24069 genes were previously predicted in the reference, and 2714 genes were novel transcripts. Moreover, 8821 genes were differentially expressed between the cultivars at the three stages. Functional analysis identified that these genes were significantly enriched in pathways carbohydrate metabolism and plant hormone signal transduction. Twenty-two genes involved in photoperiod pathway, starch metabolism and hormone signal transduction were candidate genes inducing rhizome girth enlargement. Comparative transcriptomic analysis detected several differentially expressed genes and potential candidate genes required for rhizome girth enlargement, which lay a foundation for future studies on molecular mechanisms underlying rhizome formation. PMID- 26279186 TI - Lignin-modifying processes in the rhizosphere of arid land grasses. AB - Genes associated with elevated oxidative enzyme activities in arid systems have not been well characterized. To link measured oxidative activities with specific enzymes, we assembled protein-coding reads from the rhizospheres (RHZ) of two arid land grasses. Targeted gene scans for open reading frames, encoding genes potentially involved in lignin modification, resulted in 127 distinct assembly products. The putative genes included those significantly similar to Class II secretory fungal peroxidases. These genes are expressed at sufficiently high levels for assembly, annotation and differentiation across experimental conditions, and they demonstrate the interplay of root systems, environment and plant microbiomes. The genes assembled also included copper-dependent lytic polysaccharide monooxygenases. We detail the enzymes in the host grass RHZs and present a preliminary taxonomic microhabitat characterization. Our findings provide support for biologically mediated Fenton chemistry in the root zones of desert grasses, and provide insight into arid land carbon flow. These results also demonstrate a hyperdiverse microbial community. Both ribosomal RNA and messenger RNA sequences were dominated by bacteria, followed by fungal sequence abundance. Among the notable fungal sequences were those from the members of the arbuscular mycorrhizal fungi (Glomeromycota), which though abundant in this study, we rarely observed in previous PCR-based surveys. PMID- 26279187 TI - Sex differences in the early life correlates of natural antibody concentrations. AB - Innate-like B1a lymphocytes arise from long-lived progenitors produced exclusively by fetal stem cells. Any insults coinciding with this early lymphopoietic wave could have a permanent impact on the B1a population and its unique protein products, the natural antibodies (NAb). We investigated early life nutritional influences on NAb concentrations of pre-adolescent children (n=290) in rural Nepal for whom we had extensive information on exposures from pregnancy and early infancy. Infant size and growth were strongly associated with NAb concentrations at 9-13 years of age among males (e.g., for neonatal weight: betaBOYS=0.43; P<0.001), but not females (e.g., for neonatal weight: betaGIRLS= 0.16; P=0.26). In females, season of birth was associated with NAb concentrations, with marked reductions among girls born during the pre-monsoon (March-May; betaGIRLS=-0.39; P=0.01) and pre-harvest (September-November; betaGIRLS=-0.35; P=0.03) seasons. Our findings suggest that nutritional or other environmental influences on immune development may vary by sex, with potential consequences for immune function during infancy and long-term risk of immune mediated disease. PMID- 26279188 TI - PAF1, a Molecular Regulator of Promoter-Proximal Pausing by RNA Polymerase II. AB - The control of promoter-proximal pausing and the release of RNA polymerase II (Pol II) is a widely used mechanism for regulating gene expression in metazoans, especially for genes that respond to environmental and developmental cues. Here, we identify that Pol-II-associated factor 1 (PAF1) possesses an evolutionarily conserved function in metazoans in the regulation of promoter-proximal pausing. Reduction in PAF1 levels leads to an increased release of paused Pol II into gene bodies at thousands of genes. PAF1 depletion results in increased nascent and mature transcripts and increased levels of phosphorylation of Pol II's C-terminal domain on serine 2 (Ser2P). These changes can be explained by the recruitment of the Ser2P kinase super elongation complex (SEC) effecting increased release of paused Pol II into productive elongation, thus establishing PAF1 as a regulator of promoter-proximal pausing by Pol II. PMID- 26279189 TI - Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site. AB - Epstein-Barr virus (EBV) represents a major global health problem. Though it is associated with infectious mononucleosis and ~200,000 cancers annually worldwide, a vaccine is not available. The major target of immunity is EBV glycoprotein 350/220 (gp350) that mediates attachment to B cells through complement receptor 2 (CR2/CD21). Here, we created self-assembling nanoparticles that displayed different domains of gp350 in a symmetric array. By focusing presentation of the CR2-binding domain on nanoparticles, potent neutralizing antibodies were elicited in mice and non-human primates. The structurally designed nanoparticle vaccine increased neutralization 10- to 100-fold compared to soluble gp350 by targeting a functionally conserved site of vulnerability, improving vaccine-induced protection in a mouse model. This rational approach to EBV vaccine design elicited potent neutralizing antibody responses by arrayed presentation of a conserved viral entry domain, a strategy that can be applied to other viruses. PMID- 26279190 TI - Macrophage-Induced Blood Vessels Guide Schwann Cell-Mediated Regeneration of Peripheral Nerves. AB - The peripheral nervous system has remarkable regenerative capacities in that it can repair a fully cut nerve. This requires Schwann cells to migrate collectively to guide regrowing axons across a 'bridge' of new tissue, which forms to reconnect a severed nerve. Here we show that blood vessels direct the migrating cords of Schwann cells. This multicellular process is initiated by hypoxia, selectively sensed by macrophages within the bridge, which via VEGF-A secretion induce a polarized vasculature that relieves the hypoxia. Schwann cells then use the blood vessels as "tracks" to cross the bridge taking regrowing axons with them. Importantly, disrupting the organization of the newly formed blood vessels in vivo, either by inhibiting the angiogenic signal or by re-orienting them, compromises Schwann cell directionality resulting in defective nerve repair. This study provides important insights into how the choreography of multiple cell types is required for the regeneration of an adult tissue. PMID- 26279191 TI - Sinus bradycardia, junctional rhythm, and low-rate atrial fibrillation in Short QT syndrome during 20 years of follow-up: three faces of the same genetic problem. AB - We describe the case of an asymptomatic girl with sinus bradycardia and short QT interval at birth, junctional bradycardia in infancy requiring single-chamber pacemaker, atrial fibrillation in adolescence, and V141M mutation in the KCNQ1 gene. Atrial fibrillation recurred and became unresponsive to electrical or anti arrhythmic therapy. During 20 years of follow-up, a progressive evolution from sinus node dysfunction to low-rate atrial fibrillation was observed. PMID- 26279192 TI - Continuum in the X-Z---Y weak bonds: Z= main group elements. AB - The Continuum in the variation of the X-Z bond length change from blue-shifting to red-shifting through zero- shifting in the X-Z---Y complex is inevitable. This has been analyzed by ab-initio molecular orbital calculations using Z= Hydrogen, Halogens, Chalcogens, and Pnicogens as prototypical examples. Our analysis revealed that, the competition between negative hyperconjugation within the donor (X-Z) molecule and Charge Transfer (CT) from the acceptor (Y) molecule is the primary reason for the X-Z bond length change. Here, we report that, the proper tuning of X- and Y-group for a particular Z- can change the blue-shifting nature of X-Z bond to zero-shifting and further to red-shifting. This observation led to the proposal of a continuum in the variation of the X-Z bond length during the formation of X-Z---Y complex. The varying number of orbitals and electrons available around the Z-atom differentiates various classes of weak interactions and leads to interactions dramatically different from the H-Bond. Our explanations based on the model of anti-bonding orbitals can be transferred from one class of weak interactions to another. We further take the idea of continuum to the nature of chemical bonding in general. PMID- 26279194 TI - Comparison of virulence factors and biofilm formation among Staphylococcus aureus strains isolated from human and bovine infections. AB - The aim of this study was to find different prevalence of genes involved in the biofilm formation process and to assess the phenotypic and genotypic markers of biofilm formation among Staphylococcus aureus strains isolated from human and bovine infections. In this study, 215 S. aureus strains were collected from human and dairy cow's infections. The biofilm forming capacity of the strains was evaluated using a colorimetric microtiter plate assay. The genes encoding microbial surface components, recognizing adhesive matrix molecules (MSCRAMMs) (ebpS, eno, fib, fnbA, fnbB, cna and bap), and the intracellular adhesion (ica) genes (icaA, and icaD) were targeted by polymerase chain reaction (PCR)-based method. Approximately 70% of the isolates produced biofilm. Among these, 59.3% were producers of weakly adherent biofilms while 34.8% and 5.8% produced moderate and strong biofilms, respectively. The most prevalent gene was icaD found in 88.4% of the isolates, followed by icaA, fib and eno found in 87.9%, 75.8% and 75.3% of the isolates, respectively. The bap gene was not detected in any of the isolates. The prevalence of ebpS and fnbA genes among bovine isolates were significantly higher than those in human isolates, whilst the prevalence of cna gene was significantly higher in the human isolates. In this study, a high prevalence of biofilm production was found among S. aureus strains isolated from human and bovine infections. Most biofilm producing isolates were positive for MSCRAMM, icaA, and icaD genes. PMID- 26279193 TI - Seeing Central African forests through their largest trees. AB - Large tropical trees and a few dominant species were recently identified as the main structuring elements of tropical forests. However, such result did not translate yet into quantitative approaches which are essential to understand, predict and monitor forest functions and composition over large, often poorly accessible territories. Here we show that the above-ground biomass (AGB) of the whole forest can be predicted from a few large trees and that the relationship is proved strikingly stable in 175 1-ha plots investigated across 8 sites spanning Central Africa. We designed a generic model predicting AGB with an error of 14% when based on only 5% of the stems, which points to universality in forest structural properties. For the first time in Africa, we identified some dominant species that disproportionally contribute to forest AGB with 1.5% of recorded species accounting for over 50% of the stock of AGB. Consequently, focusing on large trees and dominant species provides precise information on the whole forest stand. This offers new perspectives for understanding the functioning of tropical forests and opens new doors for the development of innovative monitoring strategies. PMID- 26279195 TI - Detection of bacteria and fungi and assessment of the molecular aspects and resistance of Escherichia coli isolated from confiscated passerines intended for reintroduction programs. AB - Many native bird species are currently considered rare in Brazil because they have been indiscriminately collected by animal traffickers and commercialized, leading to dwindling numbers in their natural habitats. Confiscated animals are at times destined for reintroduction programs that must ensure these animals do not pose a risk to native populations. Healthy or sick wild passerines may carry a great diversity of microorganisms. Therefore, knowledge of the sanitary status of confiscated animals destined for reintroduction is critical to assess whether these animals act as microorganism carriers and to investigate the epidemiology of transmissible diseases, a crucial aspect for animal and human health preservation. This study examined the occurrence of aerobic and facultative anaerobic bacteria and fungi in cloacal swabs collected from wild confiscated passerines intended for reintroduction programs. In vitro susceptibility tests of the most frequent isolates as well as studies of the molecular aspects of Escherichia coli isolates were also performed. There was microorganism growth in 62.5% of 253 samples. The microorganisms that were most frequently isolated were Staphylococcus spp. (15.0%), Micrococcus spp. (11.5%), E. coli (10.7%) and Klebsiella spp. (10.7%). Fifteen bacteria genera and seven fungi genera were isolated. Multidrug-resistance to antimicrobials was observed in Staphylococcus spp., Micrococcus spp., E. coli and Klebsiella spp. isolates. The high occurrence of Enterobacteria observed is possibly related to the sanitary conditions in which confiscated animals are usually kept. One E. coli sample (out of 27 isolates) was positive for the S-fimbrial adhesion encoding gene (sfa). Considering the low occurrence of genes that encode virulence factors, confiscated passerines may represent a low risk for the potential transmission of EPEC, APEC, UPEC and NMEC isolates to other animals or humans. The potential risk of intra- or inter-specific transmission of multidrug-resistant isolates and the introduction of these microorganisms into the environment must be considered, although there are still therapeutic alternatives for treatment of these animals among the antimicrobials which were tested. The stress and poor hygiene conditions imposed on animals during trafficking may have caused their contamination by multidrug-resistant agents transmitted by humans or by the precarious environment to which they were subjected. Risks related to the dissemination of Salmonella spp., Cryptococcus spp. and Candida spp. are low when reintroduction programs are considered. PMID- 26279196 TI - Effects of complementary whole-body vibration training in patients after lung transplantation: A randomized, controlled trial. AB - BACKGROUND: In recent years, some studies have shown that whole-body vibration training (WBVT) may be a beneficial training mode in patients with chronic obstructive pulmonary disease (COPD). However, the effects of WBVT in patients after lung transplantation (LTx) have not yet been investigated. METHODS: Eighty three LTx patients (56 +/- 7 years of age, 51% male, 10 +/- 12 weeks post-LTx, forced expiratory volume in 1 second [FEV1] 68 +/- 20 percent predicted [% pred], baseline 6-minute walk distance [6MWD] 350 +/- 120 meters) admitted to a 4-week inpatient multidisciplinary program of pulmonary rehabilitation (PR) performed supervised endurance and strength training on 5 days per week. In addition, patients were randomly assigned to 1 of 2 supervised intervention groups on 3 days/week: (1) 4 * 2 minutes of bilateral dynamic squat exercises on a side alternating vibration platform at 24 to 26 Hz (WBVT); and (2) a control group (CON) with the same amount of exercise time on the floor. RESULTS: Seventy patients completed the study (WBVT: n = 34; CON: n = 36). Improvement in 6MWD was significantly (p = 0.029) higher in the WBVT group (83.5 meters [95% CI 65.4 to 101.7]) compared with the CON group (55.2 m [95% CI 37.5 to 72.8]). Also, peak work rate increased significantly (p = 0.042) more in the WBVT group (16.8 W [95% CI 13.5 to 20.5]) than in the CON group (12.6 W [95% CI 9.0 to 16.1]). No adverse events related to the intervention occurred during the study. CONCLUSIONS: A complementary WBVT on top of conventional endurance and strength training seems to be a feasible and safe exercise modality in patients after LTx. Furthermore, it may even enhance the benefits of a comprehensive PR on exercise capacity. PMID- 26279197 TI - Post-transplant lymphoproliferative disease in heart and lung transplantation: Defining risk and prognostic factors. AB - BACKGROUND: Heart and lung transplant recipients have among of the highest incidence rates of post-transplant lymphoproliferative disease (PTLD). Despite this, there is a paucity of data specific to this group. We collated data on heart, lung and heart-lung transplant recipients with PTLD to identify disease features and prognostic factors unique to this group of patients. METHODS: Seventy cases of PTLD were identified from a single institution (41 heart, 22 lung, 6 heart-lung and 1 heart-kidney transplant) from 1984 to 2013. Demographics, immunosuppression, treatment, response, complications and survival data were analyzed. Uni- and multivariate Cox regression analyses were performed to identify prognostic factors. RESULTS: The incidence of PTLD was 7.59% in heart lung, 5.37% in heart and 3.1% in lung transplant recipients. Extranodal disease (82%) with diffuse large B-cell lymphoma (72%) was the most common presentation. Bone marrow involvement (13%) and central nervous system disease (3%) were uncommon. Heart transplant recipients had later onset of PTLD (>1 year post transplant), with less allograft involvement, compared with lung and heart-lung recipients. Poor prognostic markers were bone marrow involvement (HR 6.75, p < 0.001) and serum albumin <30 g/liter (HR 3.18, p = 0.006). Improved survival was seen with a complete response within 3 months of treatment (HR 0.08, p < 0.001). Five-year overall survival was 29%. CONCLUSION: This analysis is the largest to date on PTLD in heart and lung transplant recipients. It provides a detailed analysis of the disease in this group of patients and identifies unique prognostic features to aid risk stratification and guide treatment allocation. PMID- 26279198 TI - Internally-represented space and its mirror-reversed image of the visuospatial representation: A possible association. AB - The cognitive capacity for number representation is thought to be a functional isomorphism of space representation. Numbers are represented in a left-to-right oriented mental number line and hemispatial neglect patients consistently demonstrate rightward midline shift of visuospace, the internal space and number representation. However, patients with pathologic pain in one limb showed a negative correlation between midline shift of the visuospace and number representation. The purpose of the present study is to ascertain whether such dissociation in accessing space and number representation is observed in another neuropathic pain condition, and then to propose a theoretical model regarding an intimate relationship between visuospace and internal space representations. Using patients with deafferentation pain caused by a nerve lesion in a limb, we investigated whether number representation is closely linked to space representation by evaluating visual subjective body-midline judgments in dark and light conditions (egocentric- and allocentric-spaces, respectively). We also used a number-interval-bisection task to analyze this question. All of the patients perceived allocentric-space accurately. Respective patients showed perceptual shifts in egocentric-space and number representation, however they did not demonstrate any trend of the shifted-direction. Direct comparison revealed that number representation is negatively correlated with not allocentric-space but egocentric-space: a leftward midline-shift of egocentric-space was linked with a rightward midline-shift of number bisection, and vice-versa. Internally represented space demonstrated a mirror-reversed image of the visuospatial representation, similar to our previous finding. To explain the inverted representation, we can propose a theoretical model that spacing between mentally aligned numbers in a left-to-right sequential line is anisometric. PMID- 26279199 TI - A proposed bio-panel to predict risk for spontaneous preterm birth among African American women. AB - Preterm birth (PTB), or birth prior to 37 weeks gestation, impacts 11.5% of U.S. deliveries. PTB results in significant morbidity and mortality among affected children and imposes a large societal financial burden. Racial disparities in PTB are alarming. African American women are at more than 1.5 times the risk for PTB than white women. Unfortunately, the medical community's ability to predict who is at risk for PTB is extremely limited. History of a prior PTB remains the strongest predictor during a singleton gestation. Cervical length and fetal fibronectin measurement are helpful tools. However, usefulness is limited, particularly among the 95% of U.S. women currently pregnant and lacking a history of PTB. Therefore, preventive therapies do not reach a great number of women who may benefit from them. This manuscript, in response to the pressing need for predictors of PTB risk and elimination of racial disparities in PTB, presents a proposed bio-panel for use in predicting risk for spontaneous PTB among African American women. This bio-panel, measured each trimester, includes stimulated production of interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, IL-1 receptor antagonist (Ra), soluble(s) TNF receptor(R) 1, and sTNFR2, and cortisol responsiveness. We hypothesize that greater IL-1beta and TNF-alpha production, decreased IL-1Ra, sTNFR1, and sTNFR2 production, and decreased cortisol responsiveness at each time point as well as a more expedient alignment with this unfavorable profile over time will be associated with PTB. The choice to focus on inflammatory parameters is supported by data highlighting a crucial role for inflammation in labor. Specific inflammatory mediators have been chosen due to their potential importance in preterm labor among African American women. The bio panel also focuses on inflammatory regulation (i.e., cytokine production upon ex vivo stimulation), which is hypothesized to provide insight into potential in vivo leukocyte responses and potential for initiation of a preterm inflammatory cascade. Production of receptor antagonists is also considered, as pro inflammatory mediator effects can be greatly influenced by their balance with respective antagonists. Finally, leukocyte responsiveness to cortisol is included as a measure of cortisol's ability to convey anti-inflammatory signals. The development of a bio-panel predictive of risk for spontaneous PTB among African American women would represent a significant advancement. Available preventive therapies, namely progesterone supplementation, could be delivered to women deemed at risk. Further, the identification of biological predictors of PTB may uncover novel targets for preventive therapies. PMID- 26279200 TI - Characteristics of patients who are acutely admitted to hospital under surgical care and do not have a surgical procedure - Is there an alternative to admission? AB - INTRODUCTION: Previous work has shown that 56% of all acute surgical admissions in Ireland in 2012 did not have a formal surgical procedure. In light of the pressures on health systems internationally and the lack of relevant data on this topic in the literature, we examined the characteristics of this cohort of patients in Ireland. METHODS: Discharge data on acutely admitted patients who did not undergo a surgical procedure was extracted from the Hospital Inpatient Enquiry (HIPE) database for the year 2013. These were analysed by age, sex, diagnoses, procedures performed and length of stay in hospital. RESULTS: In 2013, 63,079 patients were admitted acutely under surgical care and then discharged without undergoing a formal surgical procedure compared to 49,903 who had a surgical procedure. Most of the discharges not having formal surgery were treated by general surgical specialities (n = 41,434) and the average length of stay was 4.8 days. Approximately half of these patients (n = 32,194) did not have any HIPE coded procedure, surgical or otherwise, during their admission into hospital. CONCLUSIONS: A considerable number of patients were admitted to Irish surgical units in 2013 and were discharged again without any formal surgical intervention. We postulate that some of these patients may not require admission to hospital and outline mechanisms which may prevent admissions Such mechanisms could allow for greater capacity for scheduled patients in currently overstrained surgical units. PMID- 26279201 TI - Isolated Roux-en-Y reconstruction versus conventional reconstruction after pancreaticoduodenectomy. AB - BACKGROUND: Pancreatic fistula (PF) is the major cause for morbidity and mortality following pancreaticoduodenectomy. The primary aim of this study was to compare the occurrence rate of postoperative PF between isolated Roux-en-Y reconstruction (RYR) and conventional reconstruction (CR) after pancreaticoduodenectomy. METHODS: Data of 43 patients who underwent RYC were compared with those of a pair-matched equal number of patients undergoing CR. We also performed a meta-analysis of comparative studies of the two procedures. RESULTS: The case-matched analysis showed no significant difference in PF occurrence between RYR and CR groups (23.3% versus 25.6%; P = 0.80). Meta analysis of 1498 patients further confirmed this finding, showing a pooled odds ratio of 1.14 (95% confidence intervals, 0.82-1.58; P = 0.43). CONCLUSION: The use of RYR for pancreaticojejunostomy does not seem to decrease the occurrence rate of postoperative PF in patients undergoing pancreaticoduodenectomy. PMID- 26279202 TI - Patient awareness and sun protection behaviour following excision of basal cell carcinoma. AB - BACKGROUND: Limited information is available regarding disease awareness and sun protection behaviour in patients previously treated for non-melanoma skin cancer. METHODS: Using a telephone-administered questionnaire, we investigated these characteristics in 250 patients in the west of Ireland who had undergone excision of basal cell carcinomas between January 2011 and December 2012. RESULTS: Only 28.8% of respondents knew that the lesion they had excised was a BCC and understood that there was a significant chance of developing another similar lesion in the next 3 years. Women and patients under age 65 were significantly better informed about their diagnosis than men (p = 0.021 and 0.000 respectively). The majority of patients (71.2%) knew that the overall effect of UV radiation on the skin was harmful and did employ some form of sun protection (avoid midday sun 72%; stay in shade 74%; wear hat 73.6%; wear sunscreen 72.8%). Females were statistically more likely to exercise better sun-protection behaviour (p = 0.002). While 76.8% of patients undertook some form of outdoor activity every day, only 22.8% wore sunscreen every day. CONCLUSIONS: Greater efforts should be made to communicate disease details and sun protection implications associated with basal cell carcinoma, especially to male patients. Improved population specific skin cancer awareness may lead to earlier detection and thus decrease both the patient morbidity and economic burden associated with locally advanced basal cell carcinoma. PMID- 26279203 TI - Lateral X-ray for proximal femoral fractures - Is it really necessary? AB - INTRODUCTION: Historically routine work up of a patient with a proximal femoral fracture always included anterior-posterior (AP) and a lateral film of the hip. The aim was to define the role of the lateral X-ray in the assessment and surgical planning of proximal femur fractures. METHODS: Radiographs of 320 consecutive patients with proximal femoral fractures who were admitted over a 12 months period were divided into lateral and AP views. Two blinded reviewers independently assessed the AP view alone and then the AP plus the lateral view. Fracture classification was noted for each X-ray and then compared with intraoperative diagnosis which was our study's gold standard. A 2 * 2 contingency square table and Pearson's x(2) test were used for statistical analysis. RESULTS: The rate of correct classification by the reviewers enhanced by the assessment of the lateral X-ray in addition to the AP view for intracapsular fractures (p = 0.018) but not for extracapsular fractures (p = 0.29). Operative management did not change for intracapsular fractures which appeared displaced on initial AP view after reviewing the lateral X-ray. The only advantage of obtaining a lateral view in intracapsular fracture was the detection of displacement were the fracture appeared to be undisplaced on initial AP view. CONCLUSIONS: This study provides statistical evidence that one view is adequate and safe for majority of proximal femoral fractures. The lateral radiograph should not be performed on a routine basis thus making considerable saving in time and money, and avoiding unnecessary radiation exposure and discomfort to the patient. PMID- 26279204 TI - A Point Mutation in PDGFRB Causes Autosomal-Dominant Penttinen Syndrome. AB - Penttinen syndrome is a distinctive disorder characterized by a prematurely aged appearance with lipoatrophy, epidermal and dermal atrophy along with hypertrophic lesions that resemble scars, thin hair, proptosis, underdeveloped cheekbones, and marked acro-osteolysis. All individuals have been simplex cases. Exome sequencing of an affected individual identified a de novo c.1994T>C p.Val665Ala variant in PDGFRB, which encodes the platelet-derived growth factor receptor beta. Three additional unrelated individuals with this condition were shown to have the identical variant in PDGFRB. Distinct mutations in PDGFRB have been shown to cause infantile myofibromatosis, idiopathic basal ganglia calcification, and an overgrowth disorder with dysmorphic facies and psychosis, none of which overlaps with the clinical findings in Penttinen syndrome. We evaluated the functional consequence of this causative variant on the PDGFRB signaling pathway by transfecting mutant and wild-type cDNA into HeLa cells, and transfection showed ligand-independent constitutive signaling through STAT3 and PLCgamma. Penttinen syndrome is a clinically distinct genetic condition caused by a PDGFRB gain-of function mutation that is associated with a specific and unusual perturbation of receptor function. PMID- 26279206 TI - Beneficial Effect of Growth Hormone Treatment on Health-Related Quality of Life in Children with Prader-Willi Syndrome: A Randomized Controlled Trial and Longitudinal Study. AB - BACKGROUND/AIMS: Growth hormone (GH) treatment is beneficial for children with Prader-Willi syndrome (PWS), but data about health-related quality of life (HRQOL) and effects of GH treatment are scarce. We, therefore, investigated the effects of GH treatment on HRQOL in PWS children. METHODS: In a randomized controlled GH trial including 26 PWS children and during an 11-year longitudinal GH study in 76 children, we annually assessed HRQOL recorded by patients and parents, using a generic questionnaire (DUX25), containing 4 subdomains (Physical, Home, Social, and Emotional) and a PWS-specific questionnaire (DUXPW). RESULTS: At baseline, PWS children rated HRQOL similar to or higher than healthy and obese children. GH-treated children reported an increase in HRQOL in the Physical and Social subdomains and the DUXPW compared to untreated children. Parents reported an increase in the Physical and Emotional subdomains and borderline in the total DUX25 compared to parents of untreated children. During the 11 years of GH treatment, the Physical subdomain continued to improve, according to parents, whereas the Home, Social and Emotional subdomains, the total DUX25, and the DUXPW remained similar, according to children and parents. CONCLUSIONS: PWS children rated HRQOL equally to or better than healthy and obese children. HRQOL increased during GH treatment, in contrast to HRQOL of untreated children. This effect was sustained during long-term GH treatment. PWS children consider themselves quite happy, despite some difficulties related to the syndrome. PMID- 26279207 TI - First reported case of a corneal abscess caused by Massilia timonae. PMID- 26279205 TI - Haploinsufficiency of the NF-kappaB1 Subunit p50 in Common Variable Immunodeficiency. AB - Common variable immunodeficiency (CVID), characterized by recurrent infections, is the most prevalent symptomatic antibody deficiency. In ~90% of CVID-affected individuals, no genetic cause of the disease has been identified. In a Dutch Australian CVID-affected family, we identified a NFKB1 heterozygous splice-donor site mutation (c.730+4A>G), causing in-frame skipping of exon 8. NFKB1 encodes the transcription-factor precursor p105, which is processed to p50 (canonical NF kappaB pathway). The altered protein bearing an internal deletion (p.Asp191_Lys244delinsGlu; p105DeltaEx8) is degraded, but is not processed to p50DeltaEx8. Altered NF-kappaB1 proteins were also undetectable in a German CVID affected family with a heterozygous in-frame exon 9 skipping mutation (c.835+2T>G) and in a CVID-affected family from New Zealand with a heterozygous frameshift mutation (c.465dupA) in exon 7. Given that residual p105 and p50 translated from the non-mutated alleles-were normal, and altered p50 proteins were absent, we conclude that the CVID phenotype in these families is caused by NF-kappaB1 p50 haploinsufficiency. PMID- 26279208 TI - Management of Infection and Febrile Neutropenia in Patients with Solid Cancer. AB - A group of experts from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Medical Oncology (SEOM) have reviewed in this paper the main aspects to be considered in the evaluation of patients with solid cancer and infectious diseases. They have established a series of recommendations on the prevention of the most prevalent infections in these patients, the use of vaccines, the control measures of vascular catheter infection and prevention of infections before certain surgical procedures. Also the criteria for management of febrile neutropenia and the use of colony stimulating factors were revised. Finally they provide a series of recommendations for the treatment of cancer patients with severe infection. The document is completed with a series of measures for the control of hospital infection. PMID- 26279209 TI - Observing accidental and intentional unusual actions is associated with different subregions of the medial frontal cortex. AB - The literature on action observation revealed contradictory results regarding the activation of different subregions of the medial prefrontal cortex when observing unusual behaviour. Error observation research has shown that the posterior part of the medial prefrontal cortex is more active when observing unusual behaviour compared to usual behaviour while action understanding research has revealed some mixed results concerning the role of the anterior part of the medial prefrontal cortex during the observation of unusual actions. Here, we resolve this discrepancy in the literature by showing that different parts of the medial prefrontal cortex are active depending on whether an observed unusual behaviour is intentional or not. While the posterior medial prefrontal cortex is more active when we observe unusual accidental actions compared to unusual intentional actions, a more anterior part of the medial prefrontal cortex is more active when we observe unusual intentional actions compared to unusual accidental actions. PMID- 26279210 TI - Brain imaging signatures of the relationship between epidermal nerve fibers and heat pain perception. AB - Although the small-diameter primary afferent fibers in the skin promptly respond to nociceptive stimuli and convey sensory inputs to the central nervous system, the neural signatures that underpin the relationship between cutaneous afferent fibers and pain perception remain elusive. We combined skin biopsy at the lateral aspect of the distal leg, which is used to quantify cutaneous afferent fibers, with fMRI, which is used to assess brain responses and functional connectivity, to investigate the relationship between cutaneous sensory nerves and the corresponding pain perception in the brain after applying heat pain stimulation to the dorsum of the right foot in healthy subjects. During painful stimulation, the degree of cutaneous innervation, as measured by epidermal nerve fiber density, was correlated with individual blood oxygen level-dependent (BOLD) signals of the posterior insular cortex and of the thalamus, periaqueductal gray, and rostral ventromedial medulla. Pain perception was associated with the activation of the anterior insular cortex and with the functional connectivity from the anterior insular cortex to the primary somatosensory cortex during painful stimulation. Most importantly, both epidermal nerve fiber density and activity in the posterior insular cortex showed a positive correlation with the strength of coupling under pain between the anterior insular cortex and the primary somatosensory cortex. Thus, our findings support the notion that the neural circuitry subserving pain perception interacts with the cerebral correlates of peripheral nociceptive fibers, which implicates an indirect role for skin nerves in human pain perception. PMID- 26279212 TI - Neural correlates of psychological resilience and their relation to life satisfaction in a sample of healthy young adults. AB - Psychological resilience refers to the ability to thrive in the face of risk and adversity, which is crucial for individuals' mental and physical health. However, its precise neural correlates are still largely unknown. Here we used resting state functional magnetic resonance imaging (rs-fMRI) to identify the brain regions underlying this construct by correlating individuals' psychological resilience scores with the regional homogeneity (ReHo) and then examined how these resilience-related regions predicted life satisfaction in a sample of healthy young adults. We found that the ReHo in the bilateral insula, right dorsal anterior cingulate cortex (dACC) and right rostral ACC (rACC) negatively predicted individual differences in psychological resilience, revealing the critical role of the salience network (SN) in psychological resilience. Crucially, the ReHo in the dACC within the SN mediated the effects of psychological resilience on life satisfaction. In summary, these findings suggest that spontaneous activity of the human brain reflect the efficiency of psychological resilience and highlight the dACC within the SN as a neural substrate linking psychological resilience and life satisfaction. PMID- 26279211 TI - Microscale spatiotemporal dynamics during neocortical propagation of human focal seizures. AB - Some of the most clinically consequential aspects of focal epilepsy, e.g. loss of consciousness, arise from the generalization or propagation of seizures through local and large-scale neocortical networks. Yet, the dynamics of such neocortical propagation remain poorly understood. Here, we studied the microdynamics of focal seizure propagation in neocortical patches (4*4 mm) recorded via high-density microelectrode arrays (MEAs) implanted in people with pharmacologically resistant epilepsy. Our main findings are threefold: (1) a newly developed stage segmentation method, applied to local field potentials (LFPs) and multiunit activity (MUA), revealed a succession of discrete seizure stages, each lasting several seconds. These different stages showed characteristic evolutions in overall activity and spatial patterns, which were relatively consistent across seizures within each of the 5 patients studied. Interestingly, segmented seizure stages based on LFPs or MUA showed a dissociation of their spatiotemporal dynamics, likely reflecting different contributions of non-local synaptic inputs and local network activity. (2) As previously reported, some of the seizures showed a peak in MUA that happened several seconds after local seizure onset and slowly propagated across the MEA. However, other seizures had a more complex structure characterized by, for example, several MUA peaks, more consistent with the succession of discrete stages than the slow propagation of a simple wavefront of increased MUA. In both cases, nevertheless, seizures characterized by spike wave discharges (SWDs, ~2-3 Hz) eventually evolved into patterns of phase-locked MUA and LFPs. (3) Individual SWDs or gamma oscillation cycles (25-60 Hz), characteristic of two different types of recorded seizures, tended to propagate with varying degrees of directionality, directions of propagation and speeds, depending on the identified seizure stage. However, no clear relationship was observed between the MUA peak onset time (in seizures where such peak onset occurred) and changes in MUA or LFP propagation patterns. Overall, our findings indicate that the recruitment of neocortical territories into ictal activity undergoes complex spatiotemporal dynamics evolving in slow discrete states, which are consistent across seizures within each patient. Furthermore, ictal states at finer spatiotemporal scales (individual SWDs or gamma oscillations) are organized by slower time scale network dynamics evolving through these discrete stages. PMID- 26279213 TI - Phospholipase A(2) enhances the endothelial cell detachment effect of a snake venom metalloproteinase in the absence of catalysis. AB - Microvessel disruption leading to hemorrhage stands among the most dangerous consequences of envenomings by snakes of the family Viperidae. A PIII metalloproteinase (SVMP), balteragin, purified from the venom of the snake Bothrops alternatus, displays a potent hemorrhagic effect, and a moderate myotoxicity in vivo. Previous studies described the ability of this SVMP to induce the detachment of C2C12 myoblasts in culture, without causing cytolysis. Surprisingly, a purified acidic phospholipase A2 (PLA2) from the same venom was found to increase this detaching activity of the SVMP on myoblasts. Since endothelial cells are a natural target of SVMPs in vivo, the possibility that this synergistic effect is also observed on this cell type was explored in the present work. In addition, a first approach of the mechanism of action of this effect was studied. Results clearly confirm that the acidic PLA2, despite lacking toxicity towards endothelial cells, significantly enhances the detaching effect of the SVMP even at a concentration as low as 1 MUg/mL. Inhibition of enzymatic activity of the PLA2 by chemical modification with p-bromophenacyl bromide did not affect the synergistic activity, suggesting that this effect is not dependent on phospholipase enzymatic activity and may instead be the consequence of an interaction of the PLA2 with endothelial cell plasma membrane. To our knowledge, this is the first report of a synergistic action of a non toxic PLA2 in enhancing the detachment of endothelial cells induced by a metalloproteinase. PMID- 26279214 TI - Bioactivation of luteolin by tyrosinase selectively inhibits glutathione S transferase. AB - Glutathione S-transferase (GST) plays a significant role in the metabolism and detoxification of drugs used in treatment of melanoma, resulting in a decrease in drug efficacy. Tyrosinase is an abundant enzyme found in melanoma. In this study, we used a tyrosinase targeted approach to selectively inhibit GST. In the presence of tyrosinase, luteolin (10 MUM) showed 87% GST inhibition; whereas in the absence of tyrosinase, luteolin led to negligible GST inhibition. With respect to GSH, both luteolin-SG conjugate and luteolin-quinone inhibited >=90% of GST activity via competitive reversible and irreversible mixed mechanisms with Ki of 0.74 MUM and 0.02 MUM, respectively. With respect to CDNB, the luteolin-SG conjugate inhibited GST activity via competitive reversible mechanism and competitively with Ki of 0.58 MUM, whereas luteolin-quinone showed irreversible mixed inhibition of GST activity with Ki of 0.039 MUM. Luteolin (100 MUM) inhibited GST in mixed manner with Ki of 53 MUM with respect to GSH and non competitively with respect to CDNB with Ki of 38 MUM. Luteolin, at a concentration range of 5-80 MUM, exhibited 78-99% GST inhibition in human SK-MEL 28 cell homogenate. Among the 3 species of intact luteolin, luteolin-SG conjugate, and luteoline-quinone, only the latter two have potential as drugs with Ki < 1 MUM, which is potentially achievable in-vivo as therapeutic agents. The order of GST inhibition was luteolin-quinone >> luteolin-SG conjugate >>> luteolin. In summary, our results suggest that luteolin was bioactivated by tyrosinase to form a luteolin-quinone and luteolin-glutathione conjugate, which inhibited GST. For the first time, in addition to intracellular GSH depletion, we demonstrate that luteolin acts as a selective inhibitor of GST in the presence of tyrosinase. Such strategy could potentially be used to selectively inhibit GST, a drug detoxifying enzyme, in melanoma cells. PMID- 26279215 TI - Ternary Inclusion Complexes of Rifaximin with beta-Cyclodextrin and Sodium Deoxycholate for Solubility Enhancement. AB - Rifaximin is a rifamycin derivative, having extremely poor aqueous solubility. The objective of present study was to improve dissolution and solubility of drug using beta-cyclodextrin inclusion complexes and also to evaluate the effect of presence of sodium deoxycholate on solubilization efficiency of beta cyclodextrin. The stochiometry of inclusion complexes of binary (drug cyclodextrin) and ternary system (drug-cyclodextrin-sodium deoxycholate) were determined by phase solubility studies at 25 degrees C. The stability constants (K1:2) calculated from phase solubility analysis were 126 M(-1) and 267 M(-1) for binary and ternary systems respectively. The inclusion complexes were prepared by solvent evaporation method with the inclusion efficiency of 43% and 56.9% for binary and ternary systems followed by their characterization using fourier transform infrared spectroscopy, X-ray diffractometry, differential scanning calorimetry and in-vitro antibacterial activity. The solubility of drug was improved by 4.3 and 11.9 folds in binary and ternary inclusion complexes, respectively. Therefore, it can be concluded that the ternary inclusion complexation having better solubilization efficiency as compared to binary complexation. PMID- 26279216 TI - Identification and expression modulation of a C-type lectin domain family 4 homologue that is highly expressed in monocytes/macrophages in rainbow trout (Oncorhynchus mykiss). AB - The C-type lectin domain containing (CLEC) receptors including CD209 are expressed in vivo by monocytes, monocyte-derived macrophages and dendritic cells and by in vitro generated monocyte-derived cells. This paper reports the cloning and sequencing of a lectin molecule, CLEC4T1, in rainbow trout that is a homologue of the CLEC4 family. The expression pattern of the CLEC4T1 was investigated in vivo after infection with a bacterial pathogen and in cultured macrophages after modulation with microbial mimics. Trout CLEC4T1 was highly expressed in spleen and head kidney following infection with Yersinia ruckeri. Expression could also be induced in macrophage cultures by LPS but not by Poly I:C, and suggests that the regulation of CLEC4T1 expression in trout varies according to the nature of the stimulant. A polyclonal CLEC4T1 antibody was generated and validated by Western blotting for use in evaluation of CLEC4T1(+) cells by flow cytometry analysis. Freshly isolated adherent trout head kidney cultures, potentially containing macrophages and dendritic cell precursors, showed an increase of CLEC4T1(+) cells (assessed by flow cytometry) upon stimulation with recombinant interleukin-4/13A. The results suggest that CLEC4T1 is a useful marker for further characterisation of monocyte derived antigen presenting cells in fish. PMID- 26279217 TI - Immune response and survival of Circulifer haematoceps to Spiroplasma citri infection requires expression of the gene hexamerin. AB - Spiroplasma citri is a cell wall-less bacterium that infects plants. It is transmitted by the leafhopper Circulifer haematoceps, which hosts this bacterium in the haemocel and insect tissues. Bacterial factors involved in spiroplasma colonization of the insect host have been identified, but the immune response of the leafhopper to S. citri infection remains unknown. In this study, we showed that C. haematoceps activates both humoral and cellular immune responses when challenged with bacteria. When infected by S. citri, C. haematoceps displayed a specific immune response, evidenced by activation of phagocytosis and upregulation of a gene encoding the protein hexamerin. S. citri infection also resulted in decreased phenoloxidase-like activity. Inhibition of hexamerin by RNA interference resulted in a significant reduction in phenoloxidase-like activity and increased mortality of infected leafhoppers. Therefore, the gene hexamerin is involved in S. citri control by interfering with insect phenoloxidase activity. PMID- 26279218 TI - Bilingual advantages in executive control - A Loch Ness Monster case or an instance of neural plasticity? PMID- 26279219 TI - Are we at a socio-political and scientific crisis? PMID- 26279220 TI - Only With a New Ruler Do You Realize the Value of the Old. PMID- 26279221 TI - Initial Experience With a Percutaneous Approach to Redo Mitral Valve Surgery: Management and Procedural Success. AB - OBJECTIVE: The purpose of the study was to report the anesthetic management and immediate procedural success in the initial 20 patients undergoing percutaneous transapical mitral valve replacement. DESIGN: Retrospective review of collected data. SETTING: University-affiliated heart center. PARTICIPANTS: Twenty patients with mitral regurgitation or stenosis due to a degenerated valve or ring in the mitral position. INTERVENTIONS: TEE-guided transapical mitral valve replacement under general anesthesia and early extubation by means of an established fast track protocol. MEASUREMENTS AND MAIN METHODS: Twenty patients underwent transapical mitral valve replacement by a beating heart procedure, avoiding cardiopulmonary bypass. The valve was either deployed due to a previously implanted bioprosthetic valve (valve-in-valve group), which degenerated, or a ring (valve-in-ring group), which predominantly showed regurgitation. There was a significant increase in the mitral valve opening area in stenosed valve pathology from 1.3-1.9 sq. cm (p = 0.004), and an increase in ejection fraction from 40% to 45% (p = 0.52). In the valve-in-ring group, valve area increased from 2.0 sq. cm to 2.6 sq. cm (p = 0.21), with an increase in ejection fraction from 30% to 35% (p = 0.18). Eighteen patients underwent successful deployment of the valve. The anesthesia duration for the procedure lasted 185.5 +/- 25.4 minutes. CONCLUSIONS: There was a significant increase in opening area of the valve and improvement in ejection fraction in this patient group. TEE and fluoroscopy-guided imaging is necessary for the procedure's success and is an evolving alternative treatment for high-risk mitral valve patients who would otherwise be considered inoperable for routine surgery using sternotomy. PMID- 26279223 TI - Transcardiopulmonary Thermodilution-Calibrated Arterial Waveform Analysis: A Primer for Anesthesiologists and Intensivists. PMID- 26279222 TI - Nutrition and the Cardiac Surgery Intensive Care Unit Patient--An Update. PMID- 26279224 TI - Pro: Focused Cardiac Ultrasound Should be an Integral Component of Anesthesiology Residency Training. PMID- 26279225 TI - Con: Perioperative Transthoracic Echocardiography Should Not Be an Integral Part of the Anesthesiology Residency Core Curriculum. PMID- 26279226 TI - Temperature Management Guidelines. PMID- 26279227 TI - The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines for Cardiopulmonary Bypass--Temperature Management During Cardiopulmonary Bypass. AB - In order to improve our understanding of the evidence-based literature supporting temperature management during adult cardiopulmonary bypass, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiology and the American Society of ExtraCorporeal Technology tasked the authors to conduct a review of the peer-reviewed literature, including: 1) optimal site for temperature monitoring, 2) avoidance of hyperthermia, 3) peak cooling temperature gradient and cooling rate, and 4) peak warming temperature gradient and rewarming rate. Authors adopted the American College of Cardiology/American Heart Association method for development clinical practice guidelines, and arrived at the following recommendations: CLASS I RECOMMENDATIONS: a)The oxygenator arterial outlet blood temperature is recommended to be utilized as a surrogate for cerebral temperature measurement during CPB. (Class I, Level C) b)To monitor cerebral perfusate temperature during warming, it should be assumed that the oxygenator arterial outlet blood temperature under-estimates cerebral perfusate temperature. (Class I, Level C) c)Surgical teams should limit arterial outlet blood temperature to<37 degrees C to avoid cerebral hyperthermia. (Class 1, Level C) d)Temperature gradients between the arterial outlet and venous inflow on the oxygenator during CPB cooling should not exceed 10 degrees C to avoid generation of gaseous emboli. (Class 1, Level C) e)Temperature gradients between the arterial outlet and venous inflow on the oxygenator during CPB rewarming should not exceed 10 degrees C to avoid out-gassing when blood is returned to the patient. (Class 1, Level C) CLASS IIa RECOMMENDATIONS: a)Pulmonary artery or nasopharyngeal temperature recording is reasonable for weaning and immediate post-bypass temperature measurement. (Class IIa, Level C)b)Rewarming when arterial blood outlet temperature >=30 degrees C: i.To achieve the desired temperature for separation from bypass, it is reasonable to maintain a temperature gradient between arterial outlet temperature and the venous inflow of<=4 degrees C. (Class IIa, Level B) ii.To achieve the desired temperature for separation from bypass, it is reasonable to maintain a rewarming rate<=0.5 degrees C/min. (Class IIa, Level B) NO RECOMMENDATION: No recommendation for a guideline is provided concerning optimal temperature for weaning from CPB due to insufficient published evidence. PMID- 26279228 TI - A retrospective study of 23 cases with subacute combined degeneration. AB - PURPOSE: To study retrospectively the diverse presentations, ancillary tests and neuroimaging in patients with subacute combined degeneration (SCD). METHODS: Twenty-three Chinese patients with SCD were included in this study. The clinical presentations and laboratory data including comprehensive metabolic panel, serum folic acid, vitamin B12 levels, gastroscopy and images of spinal cord on magnetic resonance imaging (MRI) were evaluated. Rating scales for localizations of lesions and functional disabilities were used to define the severity of neurological impairment. RESULTS: No difference was found between men and women in the age of disease onset. For most of the patients, sensory symptoms, oftentimes as initial symptoms, occurred earlier than motor symptoms. The signs of the disease were more obvious than the symptoms. Six patients had sensory deficit levels mimicking transverse myelopathy. Anemia was not always detected in our patients with SCD. Normal or even elevated serum levels of vitamin B12 were found in seven patients. Spinal cord lesions on MRI were observed in six patients and the clinical and neuroimaging findings were not necessarily consistent. CONCLUSIONS: The sensory symptoms occur earlier than the motor symptoms in SCD patients. SCD patients may have sensory deficit level. Normal or even elevated serum levels of vitamin B12 may occur in patients with SCD. PMID- 26279229 TI - Olfaction Modulates Reproductive Plasticity through Neuroendocrine Signaling in Caenorhabditis elegans. AB - Reproductive plasticity describes the ability of organisms to adjust parameters such as volume, rate, or timing of progeny production in order to maximize successful reproduction under different environmental conditions. Reproductive plasticity in response to environmental variation has been observed in a wide range of animals; however, the mechanisms involved in translating environmental cues into reproductive outcomes remain unknown. Here, we show that olfaction modulates reproductive timing and senescence through neuroendocrine signaling in Caenorhabditis elegans. On their preferred diet, worms demonstrate an increased rate of reproduction and an early onset of reproductive aging. Perception of the preferred diet's odor by AWB olfactory neurons elicits these adjustments by increasing germline proliferation, and optogenetic stimulation of AWB neurons is sufficient to accelerate reproductive timing in the absence of dietary inputs. Furthermore, AWB neurons act through neuropeptide signaling to regulate reproductive rate and senescence. These findings reveal a neuroendocrine nexus linking olfactory sensation and reproduction in response to environmental variation and indicate the significance of olfaction in the regulation of reproductive decline during aging. PMID- 26279231 TI - Distributed Attention Is Implemented through Theta-Rhythmic Gamma Modulation. AB - When subjects monitor a single location, visual target detection depends on the pre-target phase of an ~8 Hz brain rhythm. When multiple locations are monitored, performance decrements suggest a division of the 8 Hz rhythm over the number of locations, indicating that different locations are sequentially sampled. Indeed, when subjects monitor two locations, performance benefits alternate at a 4 Hz rhythm. These performance alternations were revealed after a reset of attention to one location. Although resets are common and important events for attention, it is unknown whether, in the absence of resets, ongoing attention samples stimuli in alternation. Here, we examined whether spatially specific attentional sampling can be revealed by ongoing pre-target brain rhythms. Visually induced gamma-band activity plays a role in spatial attention. Therefore, we hypothesized that performance on two simultaneously monitored stimuli can be predicted by a 4 Hz modulation of gamma-band activity. Brain rhythms were assessed with magnetoencephalography (MEG) while subjects monitored bilateral grating stimuli for a unilateral target event. The corresponding contralateral gamma-band responses were subtracted from each other to isolate spatially selective, target related fluctuations. The resulting lateralized gamma-band activity (LGA) showed opposite pre-target 4 Hz phases for detected versus missed targets. The 4 Hz phase of pre-target LGA accounted for a 14.5% modulation in performance. These findings suggest that spatial attention is a theta-rhythmic sampling process that is continuously ongoing, with each sampling cycle being implemented through gamma band synchrony. PMID- 26279230 TI - Toll-like Receptor Signaling Promotes Development and Function of Sensory Neurons Required for a C. elegans Pathogen-Avoidance Behavior. AB - Toll-like receptors (TLRs) play critical roles in innate immunity in many animal species. The sole TLR of C. elegans--TOL-1--is required for a pathogen-avoidance behavior, yet how it promotes this behavior is unknown. We show that for pathogen avoidance TOL-1 signaling is required in the chemosensory BAG neurons, where it regulates gene expression and is necessary for their chemosensory function. Genetic studies revealed that TOL-1 acts together with many conserved components of TLR signaling. BAG neurons are activated by carbon dioxide (CO2), and we found that this modality is required for pathogen avoidance. TLR signaling can therefore mediate host responses to microbes through an unexpected mechanism: by promoting the development and function of chemosensory neurons that surveil the metabolic activity of environmental microbes. PMID- 26279232 TI - Bears Show a Physiological but Limited Behavioral Response to Unmanned Aerial Vehicles. AB - Unmanned aerial vehicles (UAVs) have the potential to revolutionize the way research is conducted in many scientific fields. UAVs can access remote or difficult terrain, collect large amounts of data for lower cost than traditional aerial methods, and facilitate observations of species that are wary of human presence. Currently, despite large regulatory hurdles, UAVs are being deployed by researchers and conservationists to monitor threats to biodiversity, collect frequent aerial imagery, estimate population abundance, and deter poaching. Studies have examined the behavioral responses of wildlife to aircraft (including UAVs), but with the widespread increase in UAV flights, it is critical to understand whether UAVs act as stressors to wildlife and to quantify that impact. Biologger technology allows for the remote monitoring of stress responses in free roaming individuals, and when linked to locational information, it can be used to determine events or components of an animal's environment that elicit a physiological response not apparent based on behavior alone. We assessed effects of UAV flights on movements and heart rate responses of free-roaming American black bears. We observed consistently strong physiological responses but infrequent behavioral changes. All bears, including an individual denned for hibernation, responded to UAV flights with elevated heart rates, rising as much as 123 beats per minute above the pre-flight baseline. It is important to consider the additional stress on wildlife from UAV flights when developing regulations and best scientific practices. PMID- 26279234 TI - Attentive Tracking of Sound Sources. AB - Auditory scenes often contain concurrent sound sources, but listeners are typically interested in just one of these and must somehow select it for further processing. One challenge is that real-world sounds such as speech vary over time and as a consequence often cannot be separated or selected based on particular values of their features (e.g., high pitch). Here we show that human listeners can circumvent this challenge by tracking sounds with a movable focus of attention. We synthesized pairs of voices that changed in pitch and timbre over random, intertwined trajectories, lacking distinguishing features or linguistic information. Listeners were cued beforehand to attend to one of the voices. We measured their ability to extract this cued voice from the mixture by subsequently presenting the ending portion of one voice and asking whether it came from the cued voice. We found that listeners could perform this task but that performance was mediated by attention-listeners who performed best were also more sensitive to perturbations in the cued voice than in the uncued voice. Moreover, the task was impossible if the source trajectories did not maintain sufficient separation in feature space. The results suggest a locus of attention that can follow a sound's trajectory through a feature space, likely aiding selection and segregation amid similar distractors. PMID- 26279233 TI - Phenotypic Diversity as a Mechanism to Exit Cellular Dormancy. AB - Microorganisms can facilitate their survival in stressful environments by entering a state of metabolic inactivity or dormancy. However, this state impairs the function of the very sensory systems necessary to detect favorable growth conditions. Thus, how can a metabolically quiescent cell accurately monitor environmental conditions in order to best decide when to exit dormancy? One strategy employed by microbes to deal with changing environments is the generation of phenotypes that may be less well adapted to a current condition but might confer an advantage in the future. This bet-hedging depends on phenotypic diversity in the population, which itself can derive from naturally occurring stochastic differences in gene expression. In the case of metabolic dormancy, a bet-hedging strategy that has been proposed is the "scout model" where cells comprising a fraction of the dormant population reinitiate growth stochastically, independent of environmental cues. Here, we provide experimental evidence that such a mechanism exists in dormant spores produced by the ubiquitous soil bacterium Bacillus subtilis. We observe that these spores reinitiate growth at a low but measureable frequency even in the absence of an inducing signal. This phenomenon is the result of phenotypic variation in the propensity of individual spores to reinitiate growth spontaneously. Since this bet-hedging mechanism produces individuals that will either grow under favorable conditions or die under unfavorable conditions, a population can properly respond to environmental changes despite the impaired sensory ability of individual cells. PMID- 26279235 TI - Contrasting "Fish" Diversity Dynamics between Marine and Freshwater Environments. AB - Two theoretical models have been proposed to describe long-term dynamics of diversification: the equilibrium model considers the Earth as a closed system with a fixed maximum biological carrying capacity, whereas the expansion model hypothesizes a continuously increasing diversification of life. Based on the analysis of the fossil record of all organisms, Benton suggested contrasting models of diversity dynamics between marine and continental realms. Diversity in marine environments is characterized by phases of rapid diversification followed by plateaux, i.e., an equilibrium model directly derived from insular biogeography theories, whereas diversity in continental environments is characterized by exponential growth. Previous studies that aimed at testing these models with empirical data were based on datasets extracted directly from the reading of the vagaries of the raw fossil record, without correcting for common fossil record biases (preservation and sampling). Although correction of datasets for the incompleteness of the fossil record is now commonly performed for addressing long-term biodiversity variations, only a few attempts have been made to produce diversity curves corrected by phylogenetic data from extant and extinct taxa. Here we show that phylogenetically corrected diversity curves for "fish" (actinopterygians and elasmobranchs) during the last 200 million years fit an equilibrium model in the marine realm and an expansion model in the freshwater realm. These findings demonstrate that the rate of diversification has decreased for marine fish over the Cenozoic but is in sharp expansion for freshwater fish. PMID- 26279236 TI - Suprapubic single-incision versus conventional laparoscopic appendectomy. AB - BACKGROUND: Suprapubic single-incision laparoscopic appendectomy (SSILA), a promising new approach with potential benefits such as improved cosmetic results, has been preliminarily shown to be safe and feasible in previous single-arm studies. This study used a propensity-matched analysis to compare SSILA and conventional laparoscopic appendectomy (CLA). METHODS: Patients undergoing SSILA between March 2012 and November 2013 were matched with patients undergoing CLA during the same period at a single institution. These patient groups were compared using a propensity score analysis. The model covariates for the propensity scores included gender, age, body mass index, American Society of Anesthesiologists score, history of abdominal operation, and pathology of the resected appendix. The clinical outcomes were compared between the two groups, and the cosmetic results were evaluated via a patient scar assessment questionnaire and an objective scar evaluation scale. RESULTS: No patient in either group required additional port placement or conversion to open surgery. One patient in the SSILA group developed a wound infection, and one patient in the CLA group developed a postoperative intra-abdominal abscess. No significant differences were observed between the groups with respect to the length of hospital stay, time to semi-liquid diet, time to first flatus or hospital cost. The operative time and the number of patients requiring postoperative analgesics were greater with SSILA. Compared with CLA, SSILA was associated with better scores in the patient scar assessment questionnaire consciousness subscale and with similar scores in the appearance, satisfaction with appearance and satisfaction with symptoms subscales. The two approaches yielded similar results for the objective scar evaluation scale. CONCLUSIONS: SSILA is a feasible and safe approach with similar outcomes as CLA. SSILA results in reduced scar consciousness at the expense of relatively longer operative times and more postoperative analgesic use. PMID- 26279237 TI - Numerical Investigation of the Residual Stress Distribution of Flat-Faced and Convexly Curved Tablets Using the Finite Element Method. AB - The stress distribution of tablets after compression was simulated using a finite element method, where the powder was defined by the Drucker-Prager cap model. The effect of tablet shape, identified by the surface curvature, on the residual stress distribution was investigated. In flat-faced tablets, weak positive shear stress remained from the top and bottom die walls toward the center of the tablet. In the case of the convexly curved tablet, strong positive shear stress remained on the upper side and in the intermediate part between the die wall and the center of the tablet. In the case of x-axial stress, negative values were observed for all tablets, suggesting that the x-axial force always acts from the die wall toward the center of the tablet. In the flat tablet, negative x-axial stress remained from the upper edge to the center bottom. The x-axial stress distribution differed between the flat and convexly curved tablets. Weak stress remained in the y-axial direction of the flat tablet, whereas an upward force remained at the center of the convexly curved tablet. By employing multiple linear regression analysis, the mechanical properties of the tablets were predicted accurately as functions of their residual stress distribution. However, the multiple linear regression prediction of the dissolution parameters of acetaminophen, used here as a model drug, was limited, suggesting that the dissolution of active ingredients is not a simple process; further investigation is needed to enable accurate predictions of dissolution parameters. PMID- 26279238 TI - A Spectrum: Nephrocalcinosis-Nephrolithiasis. PMID- 26279239 TI - Sometimes a Simple Old-Fashioned and Low Cost Pathological Parameter Can be Useful. PMID- 26279241 TI - Ileal Conduits--Are They a Poor Last Resort? PMID- 26279242 TI - Salvage Surgery after Failure of Urethroplasty for Stricture Disease. PMID- 26279243 TI - Strategies for optimizing the performance of carbazole thiophene appended unsymmetrical squaraine dyes for dye-sensitized solar cells. AB - Unsymmetrical squaraine dyes (CTSQ-1 and CTSQ-2) with carbazole thiophene donor units were synthesized, characterized and used as sensitizers in dye-sensitized solar cells (DSSCs). These squaraines exhibited intense absorption in the near IR visible region of the solar spectrum both in solution and on TiO2 surface. The LUMO level of the parent sensitizer (CTSQ-2) was positioned at a potential much close to the conduction band of TiO2 resulting in lack of enough driving force for electron injection which was modulated by structurally changing the donor carbazole moiety (CTSQ-1), pushing the LUMO more positive thereby enhancing the driving force. Theoretical calculations were carried out in order to have a better understanding of the electron density distribution in CTSQ-1 and CTSQ-2. Electron injection dynamics in CTSQ-1 was studied in detail by changing the Li(+) concentration and its effects on photovoltaic parameters were discussed with the help of JV, IPCE, lifetime and EIS measurements. PMID- 26279244 TI - Electrochemical Potential Stabilization of Reconstructed Au(111) Structure by Monolayer Coverage with Graphene. AB - The electrochemical properties of a monolayer graphene grown on a Au(111) electrode were studied using cyclic voltammetry (CV) and electrochemical scanning tunneling microscopy (EC-STM). CV and EC-STM measurements in 0.1 M H2SO4 aqueous solution revealed that graphene grown on the reconstructed (22 * ?3) Au(111) structure effectively inhibited potential-induced structural transitions between reconstructed (22 * ?3) and unreconstructed (1 * 1), and the adsorption/desorption of SO4(2-) ions, which are intrinsic behavior of the bare Au(111) surface. The underlying reconstructed structure was significantly stabilized by covering with monolayer graphene over a wide potential range between -0.2 V and +1.35 V vs Ag/AgCl (saturated KCl), which is much wider than that for bare Au(111) (-0.2 to + 0.35 V vs Ag/AgCl (saturated KCl)). Such high stability has not been reported to date; therefore, these results are considered to be important for understanding the fundamentals of surface reconstruction and also serve to open a new branch of electrochemistry related to graphene/metal electrolyte interfaces. PMID- 26279245 TI - Innovation in abutment-free bone-anchored hearing devices in children: Updated results and experience. AB - INTRODUCTION: Bone-anchored hearing devices are an accepted treatment option for hearing restoration in various types of hearing loss. Traditional devices have a percutaneous abutment for attachment of the sound processor that contributes to a high complication rate. Previously, our institution reported on the Sophono (Boulder, CO, USA) abutment-free system that produced similar audiologic results to devices with abutments. Recently, Cochlear Americas (Centennial, CO, USA) released an abutment-free bone-anchored hearing device, the BAHA Attract. In contrast to the Sophono implant, the BAHA Attract utilizes an osseointegrated implant. OBJECTIVES: This study aims to demonstrate patient benefit abutment-free devices, compare the results of the two abutment-free devices, and examine complication rates. METHODS: A retrospective chart review was conducted for the first eleven Sophono implanted patients and for the first six patients implanted with the BAHA Attract at our institution. Subsequently, we analyzed patient demographics, audiometric data, clinical course and outcomes. RESULTS: Average improvement for the BAHA Attract in pure-tone average (PTA) and speech reception threshold (SRT) was 41dB hearing level (dBHL) and 56dBHL, respectively. Considering all frequencies, the BAHA Attract mean improvement was 39dBHL (range 32-45dBHL). The Sophono average improvement in PTA and SRT was 38dBHL and 39dBHL, respectively. The mean improvement with Sophono for all frequencies was 34dBHL (range 24-43dBHL). CONCLUSION: Significant improvements in both pure-tone averages and speech reception threshold for both devices were achieved. In direct comparison of the two separate devices using the chi-square test, the PTA and SRT data between the two devices do not show a statistically significant difference (p-value 0.68 and 0.56, respectively). The complication rate for these abutment free devices is lower than that of those featuring the transcutaneous abutment, although more studies are needed to further assess this potential advantage. PMID- 26279246 TI - Congenital aplasia/hypoplasia of the Epiglottis-A case report and a review of the literature. AB - IMPORTANCE: There are two clinically significant congenital anomalies of the epiglottis, aplasia and hypoplasia. Early mortality in aplasia is significantly higher than in hypoplasia. Early aggressive intervention may improve outcomes. An approach to diagnosis, treatment and outcomes is discussed. METHODS: A case of congenital aplasia of the epiglottis and a review of the literature of all the cases previously described is presented. OBSERVATIONS: A male newborn underwent microlaryngotracheobronchoscopy (MLTB) due to stridor and difficulty in establishing oral feeds and was diagnosed with congenital aplasia of the epiglottis. He has not required tracheostomy and at 11 months of follow-up is gastrostomy fed and thriving. 9 cases of aplasia and 19 cases of hypoplasia have been described previously. The difference between aplasia and hypoplasia is established based on the clinical appearance at endoscopic examination. CONCLUSIONS AND RELEVANCE: Congenital aplasia and hypoplasia of the epiglottis are rare congenital laryngeal anomalies and the majority are associated with a syndrome. Early diagnosis and management in the form of fundoplication/gastrostomy and tracheotomy when required may improve outcomes. PMID- 26279247 TI - Mutation in PCDH15 may modify the phenotypic expression of the 7511T>C mutation in MT-TS1 in a Chinese Han family with maternally inherited nonsyndromic hearing loss. AB - OBJECTIVES: Mutations in MT-TS1 have been found to be associated with nonsyndromic sensorineural hearing loss (SNHL). PCDH15 codes for protocadherin 15, a member of the cadherin superfamily of calcium-dependent cell-cell adhesion molecules. In this study, we analyzed the correlation of both MT-TS1 and PCDH15 mutations in a Chinese Han family segregating maternally inherited nonsyndromic SNHL. METHODS: We ascertained a Chinese Han family segregating maternally inherited nonsyndromic sensorineural hearing loss. Eight of 10 maternal members in this family exhibited late-onset, progressive hearing impairment. Mutation screening of 79 known deafness genes was performed for the proband by targeted next-generation sequencing. RESULTS: A total of 651 variants were detected in this individual. Among them, a homoplasmic 7511T>C variant in MT-TS1, the mitochondrial tRNA (Ser(UCN)) gene, and a heterozygous p.Asp1010Gly variant in PCDH15 were more likely to be pathogenic. Consistent with the matrilineal inheritance with reduced penetrance, the 7511T>C variant in MT-TS1 was found in all 10 maternal members and an additional heterozygous p.Asp1010Gly variant in PCDH15 cosegregated with the hearing loss in this family. CONCLUSION: Our results suggested that the PCDH15 p.Asp1010Gly variant probably modified the phenotypic expression of the 7511T>C mutation in MT-TS1. PMID- 26279248 TI - Management challenges of congenital & early onset childhood hearing loss in a sub Saharan African country. AB - BACKGROUND: Hearing impairment is a hidden human disability with potentially catastrophic and age long consequences. This study highlighted the challenges associated with the management of congenital and early onset childhood hearing loss in a sub-Saharan African country. METHODS: A retrospective descriptive study of children seen between January 2008 and December 2013 RESULT: A total of 223 children consisting of 124 (55.6%) males with (M:F) of 1.3:1. Age ranged 1-15 years (mean+/-SD; 6.39+/-4.37 years) and age group 1-5 years constituted the largest proportion (56.5%). Congenital causes, febrile illness and hypoxia were the leading causes of HI. Over 93% had moderately severe to profound hearing loss and 64.6% had delayed speech development. Majority (99.3%) with congenital/perinatal onset of HL had significantly delayed speech development and 99.3% of HL due to ototoxicity and infective causes had peri/post lingual speech impairment. Larger percentage of patients presented late; 16.6% of patients with congenital/perinatal onset of HL presented within the first year, >41% presented after the fifth year. Less than 5% had hearing aid fitted and patients with profound hearing impairment were referred for cochlear implant CONCLUSION: The burden of congenital and early onset hearing impairment is high and management outcomes are unsatisfactory in our locality, Challenges associated with managing such children were discussed, and suggestions/strategies for better management and outcome were made. PMID- 26279249 TI - The assessment of children with suspected laryngopharyngeal reflux: An Otorhinolaringological perspective. AB - The assessment of pediatric laryngopharyngeal reflux (LPR) is controversial. Otorhinolaryngologists may play a role in the evaluation of children with suspected LPR detecting typical airway endoscopic findings and/or associated diseases and may help in the selection of children to be subjected to further instrumental tests. In this perspective the present review aims at examining the available evidence in the literature regarding the assessment of LPR in children. After careful literature search there are no current validated symptoms assessment questionnaires for LPR evaluation in children; flexible fiberoptic nasopharyngolaryngoscopy remains controversial as a diagnostic tool in suspect LPR cases; even though the multichannel intraluminal impedance with pH monitoring has been proposed as the instrumental gold standard, further evidence need to be found for validation in children with typical features of LPR. PMID- 26279250 TI - A novel mutation in the PAX3 gene causes Waardenburg syndrome type I in an Iranian family. AB - OBJECTIVES: Sensorineural hearing impairment (HI) is one of the most frequent congenital defects, with a prevalence of 1 in 500 among neonates. Although there are over 400 syndromes involving HI, most cases of HI are nonsyndromic (70%), 20% of which follow autosomal dominant mode of inheritance. Waardenburg syndrome (WS) ranks first among autosomal dominant syndromic forms of HI. WS is characterized by sensorineural hearing impairment, pigmentation abnormalities of hair and skin and hypoplastic blue eyes or heterochromia iridis. WS is subdivided into four major types, WS1-WS4. WS1 is diagnosed by the presence of dystopia canthorum and PAX3 is the only gene involved. This study aims to determine the pathogenic mutation in a large Iranian pedigree affected with WS1 in order to further confirm the clinical diagnosis. METHODS: In the present study, a family segregating HI was ascertained in a genetic counseling center. Upon clinical inspection, white forelock, dystopia canthorum, broad high nasal root and synophrys, characteristic of WS1 were evident. In order to clarify the genetic etiology and confirm the clinical data, primers were designed to amplify exons and exon-intron boundaries of the responsible gene, PAX3 with 10 exons, followed by the Sanger DNA sequencing method. RESULTS: Genetic analysis of PAX3 revealed a novel mutation in PAX3 (c.1024_1040 del AGCACGATTCCTTCCAA). Our data provide genotype-phenotype correlation for the mutation in PAX3 and WS1 in the studied family, with implications for genetic counseling, which necessitates detailed clinical inspection of HI patients to distinguish syndromic HI from the more common non-syndromic cases. CONCLUSION: Our results reveal the value of phenotype directed genetic analysis and could further expand the spectrum of PAX3 mutations. PMID- 26279251 TI - The effectiveness of mentoring speech and language pathology students when they face patients with cleft palate. AB - INTRODUCTION: Mentoring programs can boost Speech & Language (SL) pathologists' satisfaction about their clinical skills, increasing their professional competence. A quality induction program provides a bridge for an efficient and comfortable transition between theoretical knowledge and clinical practice in front of clients. This transition can be especially difficult when the SL pathologist confronts patients with cleft palate. OBJECTIVE: To study whether a mentoring program can improve SL Pathology students' performance for treating patients with cleft palate. MATERIALS AND METHODS: 18 SL Pathology students coursing the third year of a SL Pathology graduate program volunteered for participating in the study. The students were divided in two groups. All SL students from both groups were equally supervised. The students were followed for two semesters during their participation in the SL Pathology intervention for patients with cleft palate. The only difference between the students from each group was that one group (active group) was mentored by an experienced SLP who had previously received specific training to become a mentor. All SL students were assessed at the onset and at the end of the study. The assessment was performed through an analysis according to a previously validated scale (Learning Continuum of Speech & Language pathologists). RESULTS: A Wilcoxon test demonstrated a significant improvement (P<0.05) in the levels of The Learning Continuum of Speech & Language Pathologists at the end of the follow-up period in both groups of students. When the levels of performance at the end were compared between groups, a Mann Whitney test demonstrated a significant difference (P<0.05). The students included in the active group who were receiving additional mentoring besides the usual clinical supervision, showed a greater improvement as compared with the students from the control group. CONCLUSIONS: Learning how to conduct an adequate and effective intervention in cleft palate patients from an integral stand point is not easy for SL students. The support and guidance of an experienced mentor seems to enhance self-confidence and improve students' performance confronting patients with cleft palate. PMID- 26279252 TI - Publication of statistically significant research findings in prosthodontics & implant dentistry in the context of other dental specialties. AB - OBJECTIVES: To assess the hypothesis that there is excessive reporting of statistically significant studies published in prosthodontic and implantology journals, which could indicate selective publication. METHODS: The last 30 issues of 9 journals in prosthodontics and implant dentistry were hand-searched for articles with statistical analyses. The percentages of significant and non significant results were tabulated by parameter of interest. Univariable/multivariable logistic regression analyses were applied to identify possible predictors of reporting statistically significance findings. The results of this study were compared with similar studies in dentistry with random-effects meta-analyses. RESULTS: From the 2323 included studies 71% of them reported statistically significant results, with the significant results ranging from 47% to 86%. Multivariable modeling identified that geographical area and involvement of statistician were predictors of statistically significant results. Compared to interventional studies, the odds that in vitro and observational studies would report statistically significant results was increased by 1.20 times (OR: 2.20, 95% CI: 1.66-2.92) and 0.35 times (OR: 1.35, 95% CI: 1.05-1.73), respectively. The probability of statistically significant results from randomized controlled trials was significantly lower compared to various study designs (difference: 30%, 95% CI: 11-49%). Likewise the probability of statistically significant results in prosthodontics and implant dentistry was lower compared to other dental specialties, but this result did not reach statistical significant (P>0.05). CONCLUSIONS: The majority of studies identified in the fields of prosthodontics and implant dentistry presented statistically significant results. The same trend existed in publications of other specialties in dentistry. PMID- 26279253 TI - Establishment and development of Echinococcus multilocularis metacestodes in the common vole (Microtus arvalis) after oral inoculation with parasite eggs. AB - Transmission of the zoonotic tapeworm, Echinococcus multilocularis mainly occurs between the red fox (Vulpes vulpes) and various species of vole. Microtus arvalis is considered one of the key intermediate hosts in Europe. We infected 21 M. arvalis aged 35 days (n=2), 56 days (n=6), 84 days (n=4) and 263 days (n=9) with 100 E. multilocularis eggs. Four voles aged 263 days were euthanized at 6 weeks post inoculation (wpi) with the remainder euthanized 10 wpi for analysis of metacestode growth and protoscolex development. Eight C57BL/6j mice (age 35-231 days) were included as controls for egg viability (they have been shown to exhibit visible infection after 4 wpi) and dissected at 6 (n=2) and 10 (n=6) wpi. M. arvalis had significantly higher metacestode establishment (p=0.008) 6 wpi with 27.5+/-6.63S.D. compared to C57BL/6j with 15.5+/-0.71S.D. Multivesiculation precluded enumeration at 10 wpi in M. arvalis. No protoscolices were found in metacestodes in M. arvalis 6 wpi or C57BL/6j at any time point but were found in all infected voles 10 wpi (48,056+/-52,574 S.D.). It has been reported that glucocorticoid (GC) profile can affect E. multilocularis establishment. This was assessed by measuring corticosterone in rodent hair to determine if parasite establishment or fertility was related to this stress hormone. No significant differences were found. Data presented here provides, for the first time, a protoscolex development window in this species that has the potential to shed light on the epizootiology of this parasite. PMID- 26279254 TI - Changes of soluble CD40 ligand in the progression of acute myocardial infarction associate to endothelial nitric oxide synthase polymorphisms and vascular endothelial growth factor but not to platelet CD62P expression. AB - Reported in vitro data implicated soluble CD40 ligand (sCD40L) in endothelial dysfunction and angiogenesis. However, whether sCD40L could exert that influence in endothelial dysfunction and angiogenesis after injury in acute myocardial infarction (AMI) patients remains unclear. In the present study, we evaluated the association of sCD40L with markers of platelet activation, endothelial, and vascular function during a recovery period early after AMI. To achieve this goal, the time changes of soluble, platelet-bound, and microparticle-bound CD40L levels over 1 month were assessed in AMI patients and correlated with endothelial nitric oxide synthase (eNOS) polymorphisms, vascular endothelial growth factor (VEGF) concentrations, and platelet expression of P-selectin (CD62P). The association of soluble form, platelet-bound, and microparticle-bound CD40L with CD62P expression on platelets, a marker of platelet activation, was also assessed to evaluate the role of CD40L in the thrombosis, whereas the association with eNOS and VEGF was to evaluate the role of CD40L in vascular dysfunction. This work shows for the first time that time changes of sCD40L over 1 month after myocardial infarct onset were associated with G894T eNOS polymorphism and with the VEGF concentrations, but not to the platelet CD62P expression. These results indicate that, in terms of AMI pathophysiology, the sCD40L cannot be consider just as being involved in thrombosis and inflammation but also as having a relevant role in vascular and endothelial dysfunction. PMID- 26279255 TI - Antibodies to high-density lipoproteins are associated with inflammation and cardiovascular disease in rheumatoid arthritis patients. AB - Several lines of evidence suggest that chronic inflammation and immune dysregulation are related to altered lipid profiles in rheumatoid arthritis (RA), but the actual mechanisms are still unclear. We wondered whether the development of antibodies against high-density lipoprotein (HDL) can be found in RA patients linked to clinical and cardiovascular (CV) risk factors. To this end, immunoglobulin G (IgG) anti-HDL antibodies and total IgG serum levels were quantified in 212 RA patients, 131 sex- and age-matched healthy controls (HC), and 52 subjects with traditional CV risk factors (tCVRs). A subgroup of 13 RA patients was prospectively followed on TNFalpha-blockade. TNFalpha, interferon (IFN)alpha, MIP1alpha, IFNgamma, IL-8, VEGF, GM-CSF, IL-17, MCP-1, SDF-1alpha, resistin, and leptin serum levels were quantified by immunoassays. IgG anti-HDL levels were higher in RA patients compared with HC (P < 0.0001) and tCVR subjects (P = 0.015). Differences with HC remained after correction for total IgG levels (P < 0.003). Anti-HDL/IgG were negatively associated with HDL levels in RA ( 1.182 [-1.823 to -0.541], P = 0.0003) after adjusting for demographical, clinical, inflammatory parameters, and treatments. RA patients with high levels of anti-HDL/IgG (n = 40, 18.8%) were more likely to have experienced a CV event (P < 0.0001) and exhibited increased levels of several proinflammatory mediators (C-reactive protein, IFNalpha, MIP1alpha, IFNgamma, IL-8, GM-CSF, IL-17 and MCP 1). Finally, change in anti-HDL antibodies on TNFalpha-blockade was independently associated with increasing HDL levels. Overall, IgG anti-HDL antibodies are increased in RA independently of tCVRs and associated with a proinflammatory milieu and impaired lipid blood profile, which may contribute to the increased rate of CV events in these patients. PMID- 26279256 TI - Evaluation and comparison of type I tympanoplasty efficacy and histopathological changes to the tympanic membrane in dry and wet ear: a prospective study. AB - OBJECTIVE: This study aimed to compare the success rate of type I tympanoplasty in active (wet) and inactive (dry) mucosal chronic otitis media. METHODS: A prospective study was performed of 35 patients each with dry ear and wet ear undergoing type I tympanoplasty in the Otolaryngology Department, Postgraduate Institute of Medical Education and Research, India. All patients underwent type I tympanoplasty between January 2010 and June 2011 by the post-auricular approach. Samples of the remnant tympanic membrane were sent for histopathological examination. RESULTS: After a minimum follow up of one year, the success rate was 88.6 per cent for dry ears and 80 per cent for wet ears. Neither the type (p = 0.526) nor the presence (p = 0.324) of discharge influenced the success rate. Histopathological examination of the tympanic membrane margins was performed for 46 patients: of these, 19 showed evidence of vascularity and 27 did not. There was no significant difference in success rate between groups (p = 0.115). CONCLUSION: The success rate was not influenced by the presence of ear discharge at the time of surgery, and tympanic membrane vascularity did not influence graft uptake. PMID- 26279257 TI - Neuroendocrine tumor of the appendix inside an incarcerated Amyand's hernia. AB - Amyand's hernia is a rare type of hernia where the vermiform appendix is within an inguinal hernia sac. Tumors of the appendix are quite uncommon. The coincidence of an Amyand's hernia with neuroendocrine tumor of the appendix, as in our case, is even more rarely reported. We report the case of an 81-year-old male who presented with an incarcerated right inguinal hernia. After resuscitation, the clinical diagnosis was confirmed by computed tomography. It showed an incarcerated right inguinal hernia which contained the distal ileum, cecum, thickened appendix, as well as a small amount of fluid. Subsequently, the patient was prepared for emergency surgery. During the operation, the hernia sac was found and opened. The appendix was swollen. Therefore, appendectomy was performed. The inguinal defect was repaired using the Modified Bassini Technique. The patient had an uneventful postoperative recovery and surprisingly the histopathology of the appendix revealed a 1.5cm well-differentiated low grade neuroendocrine tumor (carcinoid) of the appendix tip. An incidental finding of neuroendocrine tumor of the appendix in a patient with s hernia is extremely rare. A high index of suspicion is the key to diagnose such a coincidence in order to safely and optimally treat such a condition. PMID- 26279258 TI - Delayed bile leak in a patient with grade IV blunt liver trauma: A case report and review of the literature. AB - INTRODUCTION: Delayed bile leak following blunt liver trauma is not common. PRESENTATION OF CASE: We presented a case report and literature review of delayed bile leak in a young male patient who presented with grade IV blunt liver injury following a motor vehicle collision; he was a restrained driver who hit a fixed object. Physical examination was unremarkable except for revelaed tachycardia, right upper quadrant abdominal tenderness, and open left knee fracture. A diagnosis of grade IV multiple liver lacerations with large hemo-peritoneum was made and urgent exploratory laparotomy was performed. The patient developed a biloma collection post- operatively. He underwent endoscopic retrograde cholangiopancreatography (ERCP) and common bile duct stenting. His recovery was uneventful, and he was discharged home after 1 month. DISCUSSION: This is a rare case with no intra or extra hepatic biliary radicle injury seen on magnetic resonance cholangiopancreatography (MRCP) and no evidence of leak by ERCP. A review of the literature to highlight the incidence of delayed bile leak revealed only few reported cases. CONCLUSION: Our findings demonstrate the need for prompt diagnosis and treatment of delayed bile leak in blunt liver injuries. When these principles are followed, a successful outcome is possible. PMID- 26279259 TI - Trans-thoracic peri-oesophageal adjustable band for intractable reflux. AB - INTRODUCTION: Gastric bands for obesity have the beneficial side-effect of improving reflux symptoms in patients; however placement of these on patients with multiple prior abdominal surgeries can be challenging. PRESENTATION OF CASE: We present two cases where gastric bands were placed in a peri-oesophageal position via a left thoracotomy due to multiple previous abdominal surgeries in an attempt to treat their intractable reflux. DISCUSSION: At three month follow up, both patients have reported improvement in their symptoms of GORD. CONCLUSION: A peri-oesophageal position adjustable gastric band is a possible solution for patients with intractable reflux and hostile abdomens. PMID- 26279260 TI - Successful primary staple-repair of thoracic oesophagus after delayed presentation of a spontaneous perforation. AB - INTRODUCTION: Spontaneous perforation of the oesophagus is diagnosed late in over 50% of cases. Misdiagnosis may be due to atypical presentations. Primary repair is technically demanding in this setting and the risk of failure is high. PRESENTATION OF CASE: An 85 year-old lady presented with an atypical cohort of mild nonspecific symptoms in spite of a pleuro-mediastinal purulent collection secondary to an undiagnosed spontaneous perforation of the oesophagus occurred seven days before. Despite the extent of perforation (3cm in length), the late diagnosis and the necrosis of the muscular wall, the oesophagus was successfully repaired by means of a stapler. DISCUSSION: The mechanism of the atypical presentation is discussed and possible modalities of treatment of delayed oesophageal perforations are reviewed, with particular reference to primary repair and to the possible use of staplers within this setting. CONCLUSION: Even large spontaneous perforations of the oesophagus can result in a contained abscess, with no frank sepsis. Diagnosis can be missed for days in these cases. The attempt at primary repair of the oesophagus is still indicated. The use of a stapler is preferable in such cases as a perfect mucosal approximation is provided with minimal manipulation and with the use of inert, well tolerated material, which does not tend to become infected. PMID- 26279261 TI - Bony mallet finger without epiphyseal plate injury in childhood. AB - INTRODUCTION: It is commonly thought that Salter-Harris type I or II appears in mallet fingers in childhood, with S-H type III appearing in adolescence. PRESENTATION OF CASE: We present a case of bony mallet finger in childhood. Radiographs showed a small fragment above the distal interphalangeal joint, and this fragment was separated from the dorsal epiphysis without injury to the epiphyseal plate. Open reduction and fixation were performed and bone union was achieved without complications. DISCUSSION: Bony mallet finger in childhood manifests as S-H types I, II, and III in typical cases. However, it depends on narrowing of the epiphysis and the strength of the axial forces on the tip of the distal phalanx. In the case of epiphysis narrowing and only small forces affecting the region, an avulsion fracture without injury to the epiphyseal plate will occur in rare cases. CONCLUSION: We presented here a rare case of a bony mallet finger in childhood without epiphyseal plate injury. PMID- 26279262 TI - Smart surfaces based on thermo-responsive polymer brushes prepared from L-alanine derivatives for cell capture and release. AB - Two novel thermo-responsive polymer brushes were prepared from L-alanine derivatives using the surface-initiated atom transfer radical polymerization (SI ATRP) technique. The temperature-induced cell capture and release on both polymer brush modified substrates were further explored. PMID- 26279263 TI - Blue-green emitting cationic iridium complexes with 1,3,4-oxadiazole cyclometallating ligands: synthesis, photophysical and electrochemical properties, theoretical investigation and electroluminescent devices. AB - Two cationic iridium complexes, namely [Ir(dph-oxd)2(bpy)]PF6 (1) and [Ir(dph oxd)2(pzpy)]PF6 (2), using 2,5-diphenyl-1,3,4-oxadiazole (dph-oxd) as the cyclometallating ligand and 2,2'-bipyridine (bpy) or 2-(1H-pyrazol-1-yl)pyridine (pzpy) as the ancillary ligands, have been synthesized, and their photophysical and electrochemical properties have been comprehensively investigated. In solution, both complexes emit efficient blue-green light. For complex 1, the light emission in a neat film is remarkably red-shifted; in solid state, it gives an intriguing piezochromic phenomenon. Compared with archetype [Ir(ppy)2(bpy)]PF6 (ppy is 2-phenylpyridine), complex 1 shows a largely stabilized HOMO (highest occupied molecular orbital) level, induced by the electron-deficient 1,3,4 oxadiazole (oxd) heterocycle of dph-oxd, which results in an enlarged energy gap and blue-shifted emission. Compared with complex 1, complex 2 shows an enhanced LUMO (lowest unoccupied molecular orbital) level, caused by the electron-rich pzpy ancillary ligand, but they exhibit similar emission energy in solution. For both complexes, theoretical calculations reveal that their blue-green emission in solution arises primarily from the (3)pi-pi* states centered on dph-oxd; moreover, complex 1 bears close-lying (3)pi-pi* and (3)CT (charge-transfer) states, underlying its remarkably red-shifted emission in the neat film and unique piezochromic behavior in the solid state. Solid state light emitting electrochemical cells (LECs) based on complexes 1 and 2 give efficient yellow and green-blue light, with peak current efficiencies of 18.3 and 5.2 cd A(-1), respectively. It is demonstrated that oxd-type cyclometallating ligands are promising as an avenue to stabilize the HOMOs and tune emission properties of cationic iridium complexes to a large extent. PMID- 26279264 TI - HOXC10 up-regulation contributes to human thyroid cancer and indicates poor survival outcome. AB - HOX genes have been well described as important players in development and morphogenesis, and more recently, in carcinogenesis. The role and clinical implication of homeodomain-containing gene 10 (HOXC10) in human thyroid cancer is poorly understood. Real-time PCR and bioinformatics analysis were used to detect the expression of HOXC10 in normal and human thyroid cancer samples from Shanghai General Hospital (also known as Shanghai First People's Hospital) and the TCGA dataset. The survival time of patients with human thyroid cancer was also detected. Cell Count Kit-8 (CCK8) analysis was used to detect cell proliferation, and the cell cycle was assessed by flow cytometry. Migration and invasion were detected by transwell analysis. Gene set enrichment analysis (GSEA) was used to explore the correlation of HOXC10 with signaling pathways. Real-time PCR and Western blot analysis were used to detect the expression of signaling pathway related genes in human thyroid cancer cells. HOXC10 expression in Shanghai General Hospital and the TCGA dataset revealed a significant increase in human thyroid cancer tissues and its expression was positively correlated with the advanced age, poor pathologic stage, and poor prognosis. HOXC10 knockdown by shRNA conferred cell cycle blocking and inhibition of migration and invasion. GSEA in the TCGA datasets revealed that HOXC10 expression was positively correlated with cytokine-cytokine receptor interaction and chemokine signaling pathways. Our data suggest that inhibition of HOXC10 may be a therapeutic strategy for human thyroid cancer treatment. This study investigates the role and clinical implication of HOXC10 in human thyroid cancer. PMID- 26279265 TI - Spontaneous symmetry breaking of Co(II) metal-organic frameworks from achiral precursors via asymmetrical crystallization. AB - The racemic conglomerate (1P-NH3 + 1M-NH3) and enantioenriched bulk samples (1P H2O or 1M-NH3) of Co(II) metal-organic frameworks were obtained from achiral precursors under different solvothermal conditions. The bulk homochirality was generated through asymmetrical crystallization in the absence of any chiral additives confirmed by single crystal X-ray diffraction and CD spectroscopy. PMID- 26279266 TI - Human Neuropsychiatric Disease Modeling using Conditional Deletion Reveals Synaptic Transmission Defects Caused by Heterozygous Mutations in NRXN1. AB - Heterozygous mutations of the NRXN1 gene, which encodes the presynaptic cell adhesion molecule neurexin-1, were repeatedly associated with autism and schizophrenia. However, diverse clinical presentations of NRXN1 mutations in patients raise the question of whether heterozygous NRXN1 mutations alone directly impair synaptic function. To address this question under conditions that precisely control for genetic background, we generated human ESCs with different heterozygous conditional NRXN1 mutations and analyzed two different types of isogenic control and NRXN1 mutant neurons derived from these ESCs. Both heterozygous NRXN1 mutations selectively impaired neurotransmitter release in human neurons without changing neuronal differentiation or synapse formation. Moreover, both NRXN1 mutations increased the levels of CASK, a critical synaptic scaffolding protein that binds to neurexin-1. Our results show that, unexpectedly, heterozygous inactivation of NRXN1 directly impairs synaptic function in human neurons, and they illustrate the value of this conditional deletion approach for studying the functional effects of disease-associated mutations. PMID- 26279268 TI - A Quantified Scoring System for Postoperative Complication Severity Compared to the Clavien-Dindo Classification. AB - BACKGROUND/AIMS: Esophagectomies are associated with high morbidity. To assess the complication severity, the Clavien-Dindo classification (CDC) grades the most severe complication. However, it ignores additional complications that are equal or less severe. The comprehensive complication index (CCI) incorporates all complication severities. It might therefore be a better system to assess the severities. The aim of this study was to validate the CCI compared to the CDC. METHODS: A prospective database was used to analyze 621 patients, who underwent an esophagectomy between 1993 and 2005. The CCI was calculated and the relation with traditional parameters was assessed and compared to the relation of the CDC with these parameters. RESULTS: Complications occurred in 429 patients (69.1%). The correlation between the CCI and the CDC was r = 0.987, p < 0.01. The relation of the CCI with 3 out of 7 parameters was not significantly different compared to the relation of the CDC (p > 0.05). There was a significantly stronger relation (p < 0.05) of the CCI with length of stay (LOS) (r = 0.663 vs. 0.646), a prolonged LOS (r = 0.542 vs. 0.530), reintervention, (r = 0.437 vs. 0.422) and reoperation rate (0.489 vs. 0.471) than the CDC. CONCLUSION: Therefore, the CCI could be a promising scoring system that could be used to identify risks in surgical patient groups. PMID- 26279269 TI - Corticosteroids and occurrence of and mortality from infections in severe alcoholic hepatitis: a meta-analysis of randomized trials. AB - BACKGROUND & AIMS: Prednisolone is the first-line therapy for severe alcoholic hepatitis (AH). Patients with severe alcoholic hepatitis often develop severe infections that negatively impact short-term prognosis. METHODS: We performed this meta-analysis to assess the effect of corticosteroids on the occurrence of and mortality from infections in patients with severe alcoholic hepatitis. Randomized controlled trials examining the use of corticosteroids in severe alcoholic hepatitis and reporting data on infection rates and mortality were included. Random effects model was used to pool the data comparing arms with and without steroids for the occurrence of infection, 28-day mortality and cause specific mortality. RESULTS: Of 1062 patients (528 steroids treated) without infection at baseline from 12 studies, infection was reported in 213 (113 steroids treated) patients without differences comparing arms with and without steroids (OR: 0.98; CI: 0.49-1.94). However, frequency was higher for occurrence of fungal infections among steroid-treated patients (eight of 528 vs. one of 534; P = 0.02). Steroids provided mortality benefit at 28 days (OR: 0.55; CI: 0.34 0.90) mainly for liver failure-related death (OR: 0.46; CI: 0.24-0.87) without differences on mortality from infection (OR: 1.19; CI: 0.38-3.73) or gastrointestinal bleeding (OR: 0.90; CI: 0.43-1.87). Three of nine patients with fungal infections died, all in corticosteroid arm. CONCLUSIONS: Corticosteroids do not increase occurrence of or mortality from bacterial infections in patients with severe alcoholic hepatitis. Further studies are needed to develop strategies of reducing the risk of fungal infection with use of steroids for patients with severe alcoholic hepatitis. PMID- 26279267 TI - A TIM-3/Gal-9 Autocrine Stimulatory Loop Drives Self-Renewal of Human Myeloid Leukemia Stem Cells and Leukemic Progression. AB - Signaling mechanisms underlying self-renewal of leukemic stem cells (LSCs) are poorly understood, and identifying pathways specifically active in LSCs could provide opportunities for therapeutic intervention. T-cell immunoglobin mucin-3 (TIM-3) is expressed on the surface of LSCs in many types of human acute myeloid leukemia (AML), but not on hematopoietic stem cells (HSCs). Here, we show that TIM-3 and its ligand, galectin-9 (Gal-9), constitute an autocrine loop critical for LSC self-renewal and development of human AML. Serum Gal-9 levels were significantly elevated in AML patients and in mice xenografted with primary human AML samples, and neutralization of Gal-9 inhibited xenogeneic reconstitution of human AML. Gal-9-mediated stimulation of TIM-3 co-activated NF-kappaB and beta catenin signaling, pathways known to promote LSC self-renewal. These changes were further associated with leukemic transformation of a variety of pre-leukemic disorders and together highlight that targeting the TIM-3/Gal-9 autocrine loop could be a useful strategy for treating myeloid leukemias. PMID- 26279270 TI - Effects of muscle composition and architecture on specific strength in obese older women. AB - NEW FINDINGS: What is the central question of this study? Do obesity-specific factors affect skeletal muscle performance in older individuals? What is the main finding and its importance? Older obese women have a larger quadriceps femoris size but develop lower tension per unit of skeletal muscle than their normal weight counterparts. Muscle impairment and excess body mass are very common among older people. Given that the effect of obesity on strength production has scarcely been studied in older individuals, we analysed functional and structural characteristics of quadriceps femoris (QF) in obese (OB) and normal-weight (NW) older women with comparable habitual physical activity. In five OB (body mass index 36.8 +/- 1.9 kg m(-2), age 72.4 +/- 2.3 years) and six NW well-functioning older women (body mass index 24.3 +/- 1.8 kg m(-2), age 72.7 +/- 1.9 years), peak knee-extension torque (KET) was measured in isometric (90 deg knee flexion) and isokinetic conditions (240, 180, 120 and 60 deg s(-1)). Mid-thigh QF cross sectional area (CSA) and muscle tissue fat content (MF%) were determined with magnetic resonance imaging (Dixon sequence). Muscle fascicle length and pennation angle (PA) were assessed with ultrasonography for each muscle belly of the QF (vastus lateralis, vastus intermedius, rectus femoris and vastus intermedius). Despite similar values of KET, CSA was 17.0% larger in OB than in NW women (P < 0.05), so that KET/CSA was significantly lower (P < 0.05) in OB women. Compared with NW women, OB women had 28.7% higher MF% (P < 0.05) and 24.9% higher average PA (P < 0.05), while fascicle length was similar. Overall, isometric KET/CSA was negatively affected by both MF% (P < 0.05) and PA (P < 0.05), while isokinetic KET/CSA was negatively affected only by MF% (P < 0.01). Muscle composition and architecture seem to be important determinants of KET/CSA in elderly women. In fact, owing to the effect of obesity overload, OB women have a larger QF size than NW women, but unfavourable muscle composition and architecture. The higher MF% and steeper PA observed in OB women are associated with reduced levels of muscle specific strength. PMID- 26279271 TI - The effect of kinesiotape on dynamic balance following muscle fatigue in individuals with chronic ankle instability. AB - This study aimed to evaluate the effect of kinesiotape (KT) on dynamic stability following ankle muscle fatigue among individuals with chronic ankle instability (CAI). Twenty participants with CAI participated in the study. Participants were tested under three conditions: KT, non-elastic tape, and no tape pre- and post fatigue of the ankle muscles. Ankle muscles fatigue was induced using an isokinetic apparatus, activity of the fibularis muscle was recorded using one channel vibromyography (VMG), and dynamic balance and neuromuscular control were assessed using the Y-Balance Test. Following fatigue exercises, the VMG signal significantly decreased in all groups (p < 0.01), without differences between groups. No significant difference in dynamic balance test scores was found between the pre- and post-fatigue condition for each group and between groups. Our results demonstrate that KT had no significant effects on dynamic balance and muscle activity following ankle muscle fatigue among individuals with CAI. PMID- 26279272 TI - Place of family in recovery models for those with a mental illness. AB - Within the context of mental illness, there is an acknowledgement that the social environment is critical to recovery. Nonetheless, how family roles and interactions are presented in recovery frameworks is unclear. This systematic review sought to: (i) identify how family is defined in recovery models, and (ii) synthesize how family relationships and roles are incorporated into recovery models for those with a mental illness. A systematic search of electronic databases was conducted for peer reviewed, English language papers published between 1980 to April 2013, from Ovid MEDLINE, PsycINFO, Proquest, CINAHL plus and Web of Knowledge. Studies were included if they presented a recovery framework and include primary data from people with a mental illness where family was incorporated. A narrative thematic analysis was conducted on the eligible 31 studies, using inductive, open coding techniques. Eight studies did not define what was meant by 'family' while 10 studies focused exclusively on an individual's relationships with parents; six papers collected parenting demographics. Family roles included being a (adult) child, parent, spouse and being part of a 'family'. Family interactions involved being passive recipients of family support, caring for elderly parents and children and reciprocal, give and take relationships. Family interactions and roles offer the opportunity to both facilitate and impede recovery. PMID- 26279273 TI - Protein kinase C delta null mice exhibit structural alterations in articular surface, intra-articular and subchondral compartments. AB - INTRODUCTION: Structural alterations in intra-articular and subchondral compartments are hallmarks of osteoarthritis, a degenerative disease that causes pain and disability in the aging population. Protein kinase C delta (PKC-delta) plays versatile functions in cell growth and differentiation, but its role in the articular cartilage and subchondral bone is not known. METHODS: Histological analysis including alcian blue, safranin O staining and fluorochrome labeling were used to reveal structural alterations at the articular cartilage surface and bone-cartilage interface in PKC-delta knockout (KO) mice. The morphology and organization of chondrocytes were studied using confocal microscopy. Glycosaminoglycan content was studied by micromass culture of chondrocytes of PKC delta KO mice. RESULTS: We uncovered atypical structural demarcation between articular cartilage and subchondral bone of PKC-delta KO mice. Histology analyses revealed a thickening of the articular cartilage and calcified bone-cartilage interface, and decreased safranin O staining accompanied by an increase in the number of hypertrophic chondrocytes in the articular cartilage of PKC-delta KO mice. Interestingly, loss of demarcation between articular cartilage and bone was concomitant with irregular chondrocyte morphology and arrangement. Consistently, in vivo calcein labeling assay showed an increased intensity of calcein labeling in the interface of the growth plate and metaphysis in PKC-delta KO mice. Furthermore, in vitro culture of chondrocyte micromass showed a decreased alcian blue staining of chondrocyte micromass in the PKC-delta KO mice, indicative of a reduced level of glycosaminoglycan production. CONCLUSIONS: Our data imply a role for PKC-delta in the osteochondral plasticity of the interface between articular cartilage and the osteochondral junction. PMID- 26279274 TI - A new member of MocR/GabR-type PLP-binding regulator of D-alanyl-D-alanine ligase in Brevibacillus brevis. AB - The Brevibacillus brevis BBR47_28440 gene (referred to as ddlR) encodes an MocR/GabR family transcriptional regulator consisting of an N-terminal helix-turn helix DNA binding domain and a C-terminal aminotransferase-like domain. The ddlR gene is located just upstream of the d-alanyl-d-alanine ligase gene (ddl) in the B. brevis genome, and these two genes form an operon. Gel-shift assays indicated that purified DdlR binds specifically to the DNA region that includes putative 35 and -10 regions of the ddlR promoter. A 6-bp inverted repeat that overlaps the -10 region of the ddlR promoter was found to be important for the binding. In vivo reporter assays confirmed that DdlR is an activator of the ddlR-ddl operon. Spectroscopic analyses indicated that purified DdlR is a pyridoxal 5'-phosphate binding transcriptional regulator that has dipeptide binding ability for d-alanyl d-alanine, the enzymatic product of Ddl, and glycylglycine. DdlR is capable of forming a dipeptide-pyridoxal 5'-phosphate external aldimine, but it lacks aminotransferase activity. Bioinformatic analyses suggest that DdlR-mediated transcriptional regulation of ddlR and ddl may occur in multiple bacterial systems such as Actinobacteria and Bacillus species. PMID- 26279275 TI - Intrapleural Trastuzumab Therapy for Malignant Pleural Effusion from HER2 Overexpression in Metastatic Gastric Cancer. AB - BACKGROUND: Malignant pleural effusion (MPE) is an extremely common problem affecting cancer patients with advanced disease. The current therapy for MPE is local treatment, such as thoracentesis, chemical pleurodesis, intracavitary administration of anticancer drugs and systemic therapy. However, the management of MPE is still unsatisfactory. CASE: We report a case of MPE secondary to human epidermal growth factor receptor 2 (HER2)-positive gastric cancer that was successfully treated with intrapleural trastuzumab. A 52-year-old male with metastatic HER2-positive gastric cancer received chemotherapy (FOLFOX4 regimen) plus trastuzumab; after 11 courses of chemotherapy, he developed right MPE refractory to systemic treatment and pleurodesis. A pleural biopsy performed during thoracoscopy showed pleural metastasis from HER2-positive gastric cancer. The patient received 2 courses of intrapleuric trastuzumab. After the second course, the MPE disappeared, and he continued systemic therapy with trastuzumab and docetaxel. CONCLUSION: The safety was good, no local or systemic complications occurred, and the dyspnea secondary to MPE improved and subsequently disappeared. To our knowledge, this case is the first report on intrapleuric trastuzumab use to treat refractory MPE secondary to metastasis from HER2-positive gastric cancer. The treatment was well-tolerated and efficacious. PMID- 26279276 TI - Treatments for breast abscesses in breastfeeding women. AB - BACKGROUND: The benefits of breastfeeding are well known, and the World Health Organization recommends exclusive breastfeeding for the first six months of life and continuing breastfeeding to age two. However, many women stop breastfeeding due to lactational breast abscesses. A breast abscess is a localised accumulation of infected fluid in breast tissue. Abscesses are commonly treated with antibiotics, incision and drainage (I&D) or ultrasound-guided needle aspiration, but there is no consensus on the optimal treatment. OBJECTIVES: To assess the effects of different treatments for the management of breast abscesses in breastfeeding women. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trial Register (27 February 2015). In addition we searched African Journals Online (27 February 2015), Google Scholar (27 February 2015), ProQuest Dissertations and Theses Databases (27 February 2015) and the WHO International Clinical Trials Registry Platform (ICTRP) search portal (27 February 2015). We also checked reference lists of retrieved studies and contacted experts in the field as well as relevant pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials (RCTs) investigating any intervention for treating lactational breast abscesses compared with any other intervention. Studies published in abstract form, quasi-RCTs and cluster-RCTs were not eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, assessed risk of bias and extracted data. Data were checked for accuracy. MAIN RESULTS: We included six studies. Overall, trials had an unclear risk of bias for most domains due to poor reporting. Two studies did not stratify data for lactational and non-lactational breast abscesses, and these studies do not contribute to the results. This review is based on data from four studies involving 325 women. Needle aspiration (with and without ultrasound guidance) versus incision and drainage (I&D) Mean time (days) to complete resolution of breast abscess (three studies) - there was substantial heterogeneity among these data (Tau(2) = 47.63, I(2) = 97%) and a clear difference between subgroups (with or without ultrasound guidance; Chi(2) = 56.88, I(2) = 98.2%, P = < 0.00001). We did not pool these data in a meta analysis. Two studies excluded women who had treatment failure when they calculated the mean time to complete resolution. One study found that the time to complete resolution of breast abscess favoured needle aspiration over I&D (mean difference (MD) -6.07; 95% confidence interval (CI) -7.81 to -4.33; n = 36), but excluded 9/22 (41%) women in the needle aspiration group due to treatment failure. Another study reported faster resolution in the needle aspiration group (MD -17.80; 95% CI -21.27 to -14.33; n = 64) but excluded 6/35 (17%) women in the needle aspiration group due to treatment failure. A third study also reported that needle aspiration was associated with a shorter time to complete resolution of breast abscess (MD -16.00; 95%CI -18.73 to -13.27; n = 60); however, the authors did not indicate the number of women who were lost to follow-up for either group, and it is unclear how many women contributed to this result. Considering the limitations of the available data, we do not consider the results to be informative. Continuation of breastfeeding, after treatment (success): results favoured the needle aspiration group, but we did not pool data from the two studies because of substantial unexplained heterogeneity (I(2) = 97%). One study reported that women in the needle aspiration group were more likely to continue breastfeeding (risk ratio (RR) 2.89; 95% CI 1.64 to 5.08; n = 60), whereas the other study found no clear difference (RR 1.09; 95% CI 0.97 to 1.22 n = 70). Treatment failure was more common among women treated with needle aspiration compared to those who underwent I&D (RR 16.12; 95% CI 2.21 to 117.73; two studies, n = 115, low quality evidence). In one study, treatment with needle aspiration failed in 9/22 women who subsequently underwent I&D to treat their breast abscess. In another study, treatment with needle aspiration failed in 6/35 women, who subsequently underwent I&D. All abscesses in the I&D group were successfully treated.The included studies provided limited data for the review's secondary outcomes. No data were reported for adverse events. One study (60 women) reported that women in the needle aspiration group were more satisfied with their treatment than women who received I&D to treat their breast abscesses. Incision and drainage (I&D) with or without antibioticsOne study (150 women) compared the value of adding a broad-spectrum cephalosporin (single dose or a course of treatment) to women who underwent I&D for breast abscesses.The mean time to resolution of breast abscess was reported as being similar in all groups (although women with infection were excluded). Mean time to resolution for women who received a course of antibiotics was reported as 7.3 days, 6.9 days for women who received a single dose of antibiotics and 7.4 days for women who did not receive antibiotics. Standard deviations, P values and CIs were not reported and prevented further analysis. No data were reported for any continuation of breastfeeding after treatment (success). For treatment failure, there was no clear difference between the groups of women who received antibiotics (either a single dose or a course of antibiotics) and those who did not (RR 1.00; 95% CI 0.36 to 2.76).Included studies rarely reported this review's secondary outcomes (including adverse events). For post-operative complications/morbidity, there was no difference in the risk of wound infections between the antibiotics and no antibiotics groups (RR 0.58; 95% CI 0.29 to 1.17), irrespective of whether women received a single dose or a course of antibiotics. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine whether needle aspiration is a more effective option to I&D for lactational breast abscesses, or whether an antibiotic should be routinely added to women undergoing I&D for lactational breast abscesses. We graded the evidence for the primary outcome of treatment failure as low quality, with downgrading based on including small studies with few events and unclear risk of bias. PMID- 26279277 TI - Development of the Avian Dorsal Thalamus: Patterns and Gradients of Neurogenesis. AB - The dorsal thalamus is a region of the diencephalon that relays sensory and motor information between areas of the brain stem and the telencephalon. Although a dorsal thalamic region is recognized in all vertebrates and believed to be homologous, little is known about how the regions within it evolved and whether some or all regions within the dorsal thalamus are homologous among different vertebrate species. To characterize the gradients and patterns of neurogenesis of the avian dorsal thalamus, a single application of a low dose of bromodeoxyuridine (BrdU) was delivered to each chick between embryonic day (E)3 and E8 (stages 21 and 34), and chicks were followed up to E8 or E10 (stage 34 or 36). Comparisons of anti-BrdU labeling patterns across the different injection days suggest that nearly all dorsal thalamic neurons are born early in chick embryogenesis, between E3 and E8. Furthermore, neurons in the lateral, dorsal, and posterior parts of the dorsal thalamus are generally born earlier than those in the medial, ventral, and anterior parts. Analyses of the birth dates for nine regions show that the general pattern of neurogenesis in the avian dorsal thalamus resembles that of homologous regions within the rodent thalamus, with the exception of the auditory region, the nucleus ovoidalis, which is born later than the mammalian auditory medial geniculate nucleus. The similar pattern of neurogenesis in birds and mammals may represent a highly conserved developmental pattern that was present in the common ancestor of living birds and mammals, or may represent independently derived states. Additional studies in reptiles and amphibians are needed to distinguish between these evolutionary histories. PMID- 26279278 TI - Low Treatment Adherence in Pubertal Children Treated with Thyroxin or Growth Hormone. AB - BACKGROUND: Treatment outcome depends largely on treatment adherence (TA). However, studies analyzing TA in chronic endocrine diseases are scarce and controversial in childhood. PATIENTS AND METHODS: We studied TA in 103 children treated subcutaneously with growth hormone (GH) and 97 children treated orally with thyroxin. TA was calculated based on the prescription refill rates. The number of GH injections was recorded by an autoinjector device in 23 children treated with GH. RESULTS: The correlation between recorded TA and calculated TA based on prescription refill rates was very good (p < 0.001, r = 0.83). TA was lower (p < 0.01) in pubertal children compared to prepubertal children and in children self-administering their medication compared to those whose drug was administered by their parents, both in GH- and thyroxin-treated children. Overall, 67% of the pubertal children treated with GH and 58% of the pubertal children treated with thyroxin missed at least 1 dose per week. TA was higher (p < 0.001) in children with thyroxin treatment compared to children treated with recombinant human GH (8 vs. 26% missed >3 doses/week). DISCUSSION: Puberty and self-administration of drugs were negative predictors of TA. Therefore, in puberty, prevention and treatment efforts should be undertaken to improve TA, especially when adolescents administer their drugs themselves. PMID- 26279279 TI - Change of fatty acid composition of the lumbar longissimus during the final stage of fattening in the Japanese Black cattle. AB - Consideration of the shortened fattening period seems to be worthwhile for the realization of profitable beef production. In this study, change of fatty acid composition of the lumbar longissimus during the final stage of fattening was investigated in Japanese Black cattle. Each of 110 fattening animals was sampled three times: the initial two samples were taken by biopsy (25.7 months and 27.5 months on average) and the final one was from carcasses (29.9 months on average). Preliminary analysis indicated that removing muscle tissues from the constant body position of the living animals should be essential for sampling. Average monounsaturated fatty acids (MUFA) at three sampling points were 58.1%, 58.5% and 60.5%, and the differences of the third sampling with the first and second samplings were significant. Both in steers and heifers, MUFA also increased as the fattening stage proceeded, and MUFA of the heifers at all the sampling points were significantly higher than those of the steers. The increasing rate of MUFA rose from 0.21 percentage points (pp)/month at period 1 (from the first sampling to the second sampling) to 0.84 pp/month at period 2 (from the second sampling to the slaughter). PMID- 26279280 TI - Relationship between plasma homovanillic acid and outcome in patients with psychosis spectrum disorders. AB - BACKGROUND: Psychosis spectrum disorders, especially schizophrenia, have been linked to disturbed dopaminergic activity in the brain. Plasma homovanillic acid (pHVA) levels partly represent dopaminergic metabolism in the central nervous system. In the present study associations between (changes in) pHVA levels, symptom severity and symptomatic improvement in patients with psychoses were investigated. METHODS: From a total of 80 patients, 58 fulfilled all inclusion criteria and their symptom profile and severity were assessed by means of the Comprehensive Assessment of Symptoms and History (CASH), the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Scale for Severity and Improvement (CGI-S/CGI-I) at baseline and after 6 weeks of antipsychotic treatment. After inclusion, all patients were prescribed first- or second-generation antipsychotics by their treating psychiatrist. A total of 12 patients had first-episode psychosis (FEP). At both time points, pHVA levels were measured. Subsequently, pHVA levels were compared with an age-matched control sample and changes in pHVA levels (DeltapHVA) after treatment were associated with clinical parameters. RESULTS: Before analyses, data were scrutinized for possible confounders, particularly gender, smoking, medication status (including antipsychotic class), and recent drug use. The pHVA levels in patients were not different from those in controls. Treatment resulted in a significant decrease of all parameters. Symptomatic improvement as well as DeltapHVA was most pronounced in FEP patients. CONCLUSION: These findings show that patients with FEP have a more favourable outcome than non-FEP patients and that greater DeltapHVA also suggests that FEP patients still have the capacity to adjust dopaminergic neurotransmission. PMID- 26279281 TI - Partial Sequence of a Novel Virus Isolated from Pelodiscus sinensis Hemorrhagic Disease. AB - Outbreaks of hemorrhagic syndrome-like disease with high mortality rates have frequently occurred in Pelodiscus sinensis farms. The purpose of this study was to investigate the pathogen through challenge infection assays and partial sequencing of the genome of the pathogen. A 453-bp amplicon was obtained by random PCR using the nucleic acid extracted from the tissue homogenate filtrate and showed 32% identity at the amino acid level with the replicase polyprotein of the porcine reproductive and respiratory syndrome virus by Blastx. Multiple alignments indicated the putative protein sequence has some similarities to the replicase polyprotein of Arteriviridae, and the phylogenetic tree showed it was closely related to equine arteritis virus. This sequence was found in the lung of the diseased P. sinensis by in situ hybridization. Dot blot hybridization and quantitative RT-PCR showed that the lung had the highest content of virus. The peak replication of P. sinensis hemorrhagic syndrome virus (TSHSV) in the lung occurred 4 days after infection. The ribonucleic nature of the viral genome was confirmed by RNase A or DNase I treatments. We named the virus TSHSV in this study as P. sinensis is also known as Trionyx sinensis. These results provide a fundamental basis for further understanding the biology and the molecular mechanisms of TSHSV. PMID- 26279282 TI - Environmental factors that distinguish between clinical and healthy samples with childhood experiences of abuse and neglect. AB - BACKGROUND: Childhood maltreatment is associated with a wide range of problems in adulthood. However, specific environmental factors (either positive or negative) influence mental health outcomes in maltreated children. The present study investigated the effect of environmental factors by comparing a group of clinical participants with experiences of abuse/neglect with a healthy group with similar patterns of experiences. Environmental factors selected were: separation from parents, financial hardship, parental psychiatric disorders, and low social involvement. METHOD: The study included 55 mixed clinical participants and 23 healthy participants. All participants were investigated using the Childhood Experience of Care and Abuse (CECA) interview. The two groups were specifically matched with regard to patterns of childhood maltreatment. RESULTS: The findings indicated that psychopathological outcome was associated with a greater presence of negative environmental factors (p < 0.001). In particular, lack of social support seemed to be the only one predictor (OR = 27.86). CONCLUSION: This study is the first to investigate the influence of specific environmental factors in two groups with similar childhood experiences of abuse/neglect but different mental health outcomes. These findings suggest that efforts should be made to incorporate both familial and external sources of social support in promoting mental health for maltreated children. PMID- 26279283 TI - Differences in omega-3 and omega-6 polyunsaturated fatty acid consumption in people at ultra-high risk of psychosis, first-episode schizophrenia, and in healthy controls. AB - AIM: Supplementation with omega-3 PUFA showed efficacy in reducing the risk of transition into psychosis in UHR individuals. It is uncertain whether dietary patterns can be partly responsible for n-3 deficiencies observed in susceptible participants before the diagnosis of schizophrenia. The study was designed to assess differences in omega-3 and omega-6 PUFA consumption in healthy controls (HC), UHR participants and FES patients as well as to verify the hypothesis that dietary changes in PUFA consumption are present before active psychosis develops, that is, in UHR individuals. METHODS: Dietary habits during the previous year were assessed in 34 patients at UHR of psychosis, 33 patients diagnosed with FES and 33 HC participants using a validated Food-Frequency Questionnaire and the Polish Food Composition Tables. RESULTS: Significant differences in omega-3 and omega-6 PUFA intake were observed between study groups. UHR and FES groups reported significantly higher consumption of omega-6 PUFA in comparison with HC. FES patients also reported a higher consumption of alpha-linolenic acid (omega-3) in comparison with HC. No significant differences were seen in consumption of long-chain marine PUFA. CONCLUSIONS: Differences in omega-6 and omega-3 PUFA consumption exist before development of psychotic symptoms, fulfilling the criteria of schizophrenia. PMID- 26279284 TI - Streptozocin and 5-Fluorouracil for the Treatment of Pancreatic Neuroendocrine Tumors: Efficacy, Prognostic Factors and Toxicity. AB - BACKGROUND: In our center, the combination of streptozocin (STZ) and 5 fluorouracil (5-FU) has been used as the first-line treatment in the majority of patients with pancreatic neuroendocrine tumors (pNETs) over the past few decades. The objective of the current study was to assess the efficacy, prognostic factors and safety of the combination of STZ and 5-FU. PATIENTS AND METHODS: Medical records and radiological reports of 133 patients with pNETs who received the combination of STZ and 5-FU during the period 1981-2014 were retrospectively evaluated. RESULTS: The median survival from the start of treatment was 51.9 months in the whole group. In the radiologically evaluable patients (n = 100), progression-free survival was 23 months. Complete response was reached in 3 patients (3%), partial response in 25 patients (25%), 64 patients (64%) had stable disease, and 8 patients (8%) had progressive disease. In a multivariate analysis, surgery of the primary tumor and having a G3 tumor were significant positive and negative prognostic factors of survival from the start of treatment, respectively. Having either a G3 tumor or a stage IV tumor were significant prognostic factors for a shorter progression-free survival. Chemotherapy had to be discontinued in 29 patients due to side effects, of which kidney toxicity (mainly grades 1-2) was the most frequent. CONCLUSION: As shown in recent reports, the combination of STZ and 5-FU is effective in the treatment of pNETs in terms of survival and radiological response and has an acceptable toxicity profile. PMID- 26279285 TI - Responses of wheat and rice to factorial combinations of ambient and elevated CO2 and temperature in FACE experiments. AB - Elevated CO2 and temperature strongly affect crop production, but understanding of the crop response to combined CO2 and temperature increases under field conditions is still limited while data are scarce. We grew wheat (Triticum aestivum L.) and rice (Oryza sativa L.) under two levels of CO2 (ambient and enriched up to 500 MUmol mol(-1) ) and two levels of canopy temperature (ambient and increased by 1.5-2.0 degrees C) in free-air CO2 enrichment (FACE) systems and carried out a detailed growth and yield component analysis during two growing seasons for both crops. An increase in CO2 resulted in higher grain yield, whereas an increase in temperature reduced grain yield, in both crops. An increase in CO2 was unable to compensate for the negative impact of an increase in temperature on biomass and yield of wheat and rice. Yields of wheat and rice were decreased by 10-12% and 17-35%, respectively, under the combination of elevated CO2 and temperature. The number of filled grains per unit area was the most important yield component accounting for the effects of elevated CO2 and temperature in wheat and rice. Our data showed complex treatment effects on the interplay between preheading duration, nitrogen uptake, tillering, leaf area index, and radiation-use efficiency, and thus on yield components and yield. Nitrogen uptake before heading was crucial in minimizing yield loss due to climate change in both crops. For rice, however, a breeding strategy to increase grain number per m(2) and % filled grains (or to reduce spikelet sterility) at high temperature is also required to prevent yield reduction under conditions of global change. PMID- 26279286 TI - Temporal Trends in Bleeding among Acute Coronary Syndrome Patients: Is It Going Up or Down? Does It Matter? PMID- 26279287 TI - Increased exhaled breath condensate 8-isoprostane after a swimming session in competitive swimmers. AB - OBJECTIVES: This study aimed to evaluate the levels of 8-isoprostane (8-IsoP) in the airways of competitive swimmers at baseline and after a swimming session according to their airway responsiveness. METHODS: Twenty-three swimmers and six lifeguards had a baseline spirometry and bronchoprovocative challenges. During a second visit, swimmers performed a usual swimming session while lifeguards stayed in the same pool environment for the same time period. Forced expiratory volume in one second (FEV1) was measured before and 5 min after the end of the session. Exhaled breath condensate (EBC) was sampled before and 10 min after the session and EBC 8-IsoP levels were analysed by enzyme immunoassay. Change in EBC 8-IsoP from baseline to post-swimming session was calculated. RESULTS: We observed no relationships between airway hyper-responsiveness and 8-IsoP values before or after swimming in swimmers. The levels of 8-IsoP were significantly higher after the training session (mean value 2.9, s = 0.5 pg mL(-1)) than at baseline (mean value 1.9, s = 0.4 pg mL(-1)) in swimmers only (p = .012). EBC 8-IsoP levels after the swimming session significantly correlated with the percent change in FEV1 after swimming. CONCLUSIONS: EBC 8-IsoP levels were increased after training in swimmers but not in lifeguards, suggesting that exercise-induced hyperpnoea in a chlorinated pool environment increases airways oxidative stress. PMID- 26279288 TI - Cutaneous melanoma: how to improve the quality of diagnosis and treatment - a regional experience. PMID- 26279289 TI - T-cell homeostasis in chronic HCV-infected patients treated with interferon and ribavirin or an interferon-free regimen. AB - Direct-acting antiviral has replaced pegylated interferon-alpha and ribavirin based treatment in the treatment of chronic hepatitis C virus (HCV) infection. While interferon-alpha is immune modulating and causes lymphopenia, interferon free regimens seem to be well-tolerated. This study aimed to compare T-cell homeostasis before, during, and after HCV treatment with or without interferon alpha in patients with chronic HCV infection. A total of 20 patients with chronic HCV infection were treated with pegylated interferon-alpha and ribavirin, and six patients were treated with an interferon-free regimen. All patients were treated for a minimum of 12 weeks. Interferon-alpha treatment caused an increase in the density of the receptor for IL-7 (IL-7Ralpha) during treatment, while interferon free regimens caused a decrease in IL-7Ralpha density. After a sustained viral response, proportions of IL-7Ralpha+ T cells and IL-7Ralpha density decreased compared to prior treatment values. Finally, a proportion of CD8+ effector memory was lower while proportion of apoptotic T cells was higher after sustained virologic response compared to prior treatment. Despite lymphopenia during interferon, alterations in T-cell homeostasis during treatment were relatively similar in patients receiving interferon-based treatment and in patients receiving interferon-free treatment, and alterations during and after treatment seem to illustrate a reduced need for high levels of T cells aimed at controlling infection. PMID- 26279290 TI - Dietary Fiber Consumption Decreases the Risks of Overweight and Hypercholesterolemia in Japanese Children. AB - AIMS: It remains inconclusive whether high dietary fiber intake decreases the risk of obesity, hypercholesterolemia or high blood pressure during childhood. Therefore, this study investigated the relationships of dietary fiber intake with weight status and related clinical parameters among Japanese children. METHODS: We analyzed the data of 5,600 subjects aged 10-11 years, between 2006 and 2010. Fiber intake was assessed using the Brief-type Diet History Questionnaire. Body height and weight and blood pressure were measured. Serum levels of total cholesterol, low- and high-density lipoprotein cholesterol and triglycerides were analyzed. Fiber intake was categorized into quintiles, and multivariate models were used to adjust for lifestyle factors. RESULTS: Total fiber intake decreased the risks of overweight and high total cholesterol (OR Quintile 5 vs. Quintile 1 overweight: 0.71 for boys, 0.40 for girls; total cholesterol: 0.60 for boys, 0.66 for girls). Water-soluble fiber intake was associated with a lower risk of high blood pressure, although the ORs were not significant. CONCLUSIONS: Increasing the dietary fiber intake in Japanese children may have favorable effects on overweight and hypercholesterolemia. PMID- 26279292 TI - Population based ranking of frameless CT-MRI registration methods. AB - BACKGROUND: Clinical practice often requires simultaneous information obtained by two different imaging modalities. Registration algorithms are commonly used for this purpose. Automated procedures are very helpful in cases when the same kind of registration has to be performed on images of a high number of subjects. Radiotherapists would prefer to use the best automated method to assist therapy planning, however there are not accepted procedures for ranking the different registration algorithms. PURPOSE: We were interested in developing a method to measure the population level performance of CT-MRI registration algorithms by a parameter of values in the [0,1] interval. MATERIALS AND METHODS: Pairs of CT and MRI images were collected from 1051 subjects. Results of an automated registration were corrected manually until a radiologist and a neurosurgeon expert both accepted the result as good. This way 1051 registered MRI images were produced by the same pair of experts to be used as gold standards for the evaluation of the performance of other registration algorithms. Pearson correlation coefficient, mutual information, normalized mutual information, Kullback-Leibler divergence, L1 norm and square L2 norm (dis)similarity measures were tested for sensitivity to indicate the extent of (dis)similarity of a pair of individual mismatched images. RESULTS: The square Hellinger distance proved suitable to grade the performance of registration algorithms at population level providing the developers with a valuable tool to rank algorithms. CONCLUSIONS: The developed procedure provides an objective method to find the registration algorithm performing the best on the population level out of newly constructed or available preselected ones. PMID- 26279291 TI - Intermediate Diastolic Velocity as a Parameter of Cardiac Dysfunction in Growth Restricted Fetuses. AB - OBJECTIVE: To evaluate the intermediate intracardiac diastolic velocities in fetuses with growth restriction. METHODS: Doppler waveforms of the two atrioventricular valves were obtained. Peak velocities of the E (early) and A (atrial) components, and the lowest intermediate velocity (IDV) between them, were measured in 400 normally grown and in 100 growth-restricted fetuses. The prevalence of abnormal IDV, E/IDV, and A/IDV ratios in fetuses presenting with perinatal death or acidemia at birth (pH <=7.1) was estimated. RESULTS: IDV was significantly lower and E/IDV ratios significantly higher in the two ventricles of growth-restricted fetuses with reduced diastolic velocities in the umbilical artery (p < 0.05). In 13 fetuses presenting with perinatal death or acidemia at birth, 11 (85%) had either an E/IDV or A/IDV ratio >95th percentile, whereas 5 (38%) showed absent or reversed atrial velocities in the ductus venosus (DV-ARAV; p < 0.04). Fetuses without DV-ARAV but with elevated E/IDV ratios in either ventricle were nearly 7-fold more likely to have perinatal demise or acidemia at birth (OR 6.9, 95% CI 1.4-34) than those with E/IDV ratios <95th percentile. CONCLUSION: The E/IDV and A/IDV ratios in the two cardiac ventricles might provide information about the risk of perinatal demise or acidemia in growth restricted fetuses. PMID- 26279293 TI - ITPA and SLC29A1 Genotyping for the Prediction of Ribavirin Dose Reduction in Anti-HCV Triple Therapy with Protease Inhibitors. AB - Chronic hepatitis C is one of the most important causes of liver disease, leading to cirrhosis, hepatic decompensation and hepatocellular carcinoma. Recently some important advances in therapy have been achieved with the introduction of first wave, first generation direct acting antiviral agents (DAAs) such as boceprevir (BOC), in combination with pegylated interferon (Peg-IFN) and ribavirin (RBV). The superior rate of sustained virological response with this treatment is accompanied by an elevated frequency of anaemia. Several studies have evidenced the importance of single nucleotide polymorphisms (SNPs) in inosine triphosphatase (ITPA) and solute carrier family 29, member 1 (SLC29A1) genes in the development of this adverse event. Here, we investigated haemoglobin levels and the best-known functional SNPs in ITPA and SLC29A1 genes in 22 patients treated with triple therapy with BOC/Peg-IFN/RBV. The identification of ITPA protective and SLC29A1 risk genotypes still appears to be a current methodology in RBV dosing during hepatitis C virus therapy with DAAs. PMID- 26279294 TI - Comparing Short- and Long-Term Group Therapy: Seven-Year Follow-Up of a Randomized Clinical Trial. PMID- 26279295 TI - Targeted inhibition of metastatic melanoma through interference with Pin1-FOXM1 signaling. AB - Melanoma is the most lethal form of skin cancer and successful treatment of metastatic melanoma remains challenging. BRAF/MEK inhibitors only show a temporary benefit due to rapid occurrence of resistance, whereas immunotherapy is mainly effective in selected subsets of patients. Thus, there is a need to identify new targets to improve treatment of metastatic melanoma. To this extent, we searched for markers that are elevated in melanoma and are under regulation of potentially druggable enzymes. Here, we show that the pro-proliferative transcription factor FOXM1 is elevated and activated in malignant melanoma. FOXM1 activity correlated with expression of the enzyme Pin1, which we found to be indicative of a poor prognosis. In functional experiments, Pin1 proved to be a main regulator of FOXM1 activity through MEK-dependent physical regulation during the cell cycle. The Pin1-FOXM1 interaction was enhanced by BRAF(V600E), the driver oncogene in the majority of melanomas, and in extrapolation of the correlation data, interference with? Pin1 in BRAF(V600E)-driven metastatic melanoma cells impaired both FOXM1 activity and cell survival. Importantly, cell permeable Pin1-FOXM1-blocking peptides repressed the proliferation of melanoma cells in freshly isolated human metastatic melanoma ex vivo and in three dimensional-cultured patient-derived melanoids. When combined with the BRAF(V600E)-inhibitor PLX4032 a robust repression in melanoid viability was obtained, establishing preclinical value of patient-derived melanoids for prognostic use of drug sensitivity and further underscoring the beneficial effect of Pin1-FOXM1 inhibitory peptides as anti-melanoma drugs. These proof-of-concept results provide a starting point for development of therapeutic Pin1-FOXM1 inhibitors to target metastatic melanoma. PMID- 26279296 TI - Myeloid-specific TGF-beta signaling in bone promotes basic-FGF and breast cancer bone metastasis. AB - Breast cancer (BCa) bone metastases cause osteolytic bone lesions, which result from the interactions of metastatic BCa cells with osteoclasts and osteoblasts. Osteoclasts differentiate from myeloid lineage cells. To understand the cell specific role of transforming growth factor beta (TGF-beta) in the myeloid lineage, in BCa bone metastases, MDA-MB-231 BCa cells were intra-tibially or intra-cardially injected into LysM(Cre)/Tgfbr2(floxE2/floxE2) knockout (LysM(Cre)/Tgfbr2 KO) or Tgfbr2(floxE2/floxE2) mice. Metastatic bone lesion development was compared by analysis of both lesion number and area. We found that LysM(Cre)/Tgfbr2 knockout significantly decreased MDA-MB-231 bone lesion development in both the cardiac and tibial injection models. LysM(Cre)/Tgfbr2 knockout inhibited the tumor cell proliferation, angiogenesis and osteoclastogenesis of the metastatic bones. Cytokine array analysis showed that basic fibroblast growth factor (bFGF) was downregulated in MDA-MB-231-injected tibiae from the LysM(Cre)/Tgfbr2 KO group, and intravenous injection of the recombinant bFGF to LysM(Cre)/Tgfbr2 KO mice rescued the inhibited metastatic bone lesion development. The mechanism by which bFGF rescued the bone lesion development was by promotion of tumor cell proliferation through the downstream mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK)-cFos pathway after binding to the FGF receptor 1 (FGFR1). Consistent with animal studies, we found that in human BCa bone metastatic tissues, TGF-beta type II receptor (TbetaRII) and p-Smad2 were expressed in osteoclasts and tumor cells, and were correlated with the expression of FGFR1. Our studies suggest that myeloid-specific TGF-beta signaling-mediated bFGF in the bone promotes BCa bone metastasis. PMID- 26279297 TI - PKCiota promotes ovarian tumor progression through deregulation of cyclin E. AB - The high frequency of relapse of epithelial ovarian tumors treated with standard chemotherapy has highlighted the necessity to identify targeted therapies that can improve patient outcomes. The dynamic relationship between cyclin E and PKCiota frequent overexpression in high-grade ovarian tumors poses a novel pathway for therapeutic investigation. We hypothesized that a phosphoinositide 3 kinase (PI3K)-dependent signaling pathway activating PKCiota perpetuates cyclin E deregulation during ovarian tumorigenesis. We observed a positive correlation between PKCiota and cyclin E in a panel of 19 ovarian cancer cell lines. Modulation of cyclin E had no effect on PKCiota knockdown/overexpression; however, PKCiota differentially regulated cyclin E expression. In the serous ovarian cancer cells (IGROV and OVCAR-3), shPKCiota decreased proliferation, caused a G1 arrest and significantly prolonged overall survival in xenograft mouse models. In vitro, shPKCiota decreased the ability of IGROV cells to grow under anchorage-independent conditions and form aberrant acini, which was dependent on Ad-cyclin E or Ad-LMW-E expression. Reverse-phase protein array analysis of PKCiota wild-type, catalytic active, dominant-negative protein isoforms strengthened the association between phospho-PKCiota levels and PI3K pathway activation. Inhibitors of PI3K coordinately decreased phospho-PKCiota and cyclin E protein levels. In conclusion, we have identified a PI3K/PKCiota/cyclin E signaling pathway as a therapeutic target during ovarian tumorigenesis. PMID- 26279298 TI - Regulation of c-Myc expression by the histone demethylase JMJD1A is essential for prostate cancer cell growth and survival. AB - The histone demethylase JMJD1A, which controls gene expression by epigenetic regulation of H3K9 methylation marks, functions in diverse activities, including spermatogenesis, metabolism and stem cell self-renewal and differentiation. Here, we found that JMJD1A knockdown in prostate cancer cells antagonizes their proliferation and survival. Profiling array analyses revealed that JMJD1A dependent genes function in cellular growth, proliferation and survival, and implicated that the c-Myc transcriptional network is deregulated following JMJD1A inhibition. Biochemical analyses confirmed that JMJD1A enhances c-Myc transcriptional activity by upregulating c-Myc expression levels. Mechanistically, JMJD1A activity promoted recruitment of androgen receptor (AR) to the c-Myc gene enhancer and induced H3K9 demethylation, increasing AR dependent transcription of c-Myc mRNA. In parallel, we found that JMJD1A regulated c-Myc stability, likely by inhibiting HUWE1, an E3 ubiquitin ligase known to target degradation of several substrates including c-Myc. JMJD1A (wild type or mutant lacking histone demethylase activity) bound to HUWE1, attenuated HUWE1-dependent ubiquitination and subsequent degradation of c-Myc, increasing c Myc protein levels. Furthermore, c-Myc knockdown in prostate cancer cells phenocopied effects of JMJD1A knockdown, and c-Myc re-expression in JMJD1A knockdown cells partially rescued prostate cancer cell growth in vitro and in vivo. c-Myc protein levels were positively correlated with those of JMJD1A in a subset of human prostate cancer specimens. Collectively, our findings identify a critical role for JMJD1A in regulating proliferation and survival of prostate cancer cells by controlling c-Myc expression at transcriptional and post translational levels. PMID- 26279299 TI - Onco-exaptation of an endogenous retroviral LTR drives IRF5 expression in Hodgkin lymphoma. AB - The transcription factor interferon regulatory factor 5 (IRF5) is upregulated in Hodgkin lymphoma (HL) and is a key regulator of the aberrant transcriptome characteristic of this disease. Here we show that IRF5 upregulation in HL is driven by transcriptional activation of a normally dormant endogenous retroviral LOR1a long terminal repeat (LTR) upstream of IRF5. Specifically, through screening of RNA-sequencing libraries, we detected LTR-IRF5 chimeric transcripts in multiple HL cell lines but not in normal B-cell controls. In HL, the LTR was in an open and hypomethylated epigenetic state, and we further show the LTR is the site of transcriptional initiation. Among HL cell lines, usage of the LTR promoter strongly correlates with overall levels of IRF5 mRNA and protein, indicating that LTR transcriptional awakening is a major contributor to IRF5 upregulation in HL. Taken together, oncogenic IRF5 overexpression in HL is the result of a specific LTR transcriptional activation. We propose that such LTR derepression is a distinct mechanism of oncogene activation ('onco-exaptation'), and that such a mechanism warrants further investigation in molecular and cancer research. PMID- 26279300 TI - Apolipoprotein A-I inhibits experimental colitis and colitis-propelled carcinogenesis. AB - In both humans with long-standing ulcerative colitis and mouse models of colitis associated carcinogenesis (CAC), tumors develop predominantly in the distal part of the large intestine but the biological basis of this intriguing pathology remains unknown. Herein we report intrinsic differences in gene expression between proximal and distal colon in the mouse, which are augmented during dextran sodium sulfate (DSS)/azoxymethane (AOM)-induced CAC. Functional enrichment of differentially expressed genes identified discrete biological pathways operating in proximal vs distal intestine and revealed a cluster of genes involved in lipid metabolism to be associated with the disease-resistant proximal colon. Guided by this finding, we have further interrogated the expression and function of one of these genes, apolipoprotein A-I (ApoA-I), a major component of high-density lipoprotein. We show that ApoA-I is expressed at higher levels in the proximal compared with the distal part of the colon and its ablation in mice results in exaggerated DSS-induced colitis and disruption of epithelial architecture in larger areas of the large intestine. Conversely, treatment with an ApoA-I mimetic peptide ameliorated the phenotypic, histopathological and inflammatory manifestations of the disease. Genetic interference with ApoA-I levels in vivo impacted on the number, size and distribution of AOM/DSS-induced colon tumors. Mechanistically, ApoA-I was found to modulate signal transducer and activator of transcription 3 (STAT3) and nuclear factor-kappaB activation in response to the bacterial product lipopolysaccharide with concomitant impairment in the production of the pathogenic cytokine interleukin-6. Collectively, these data demonstrate a novel protective role for ApoA-I in colitis and CAC and unravel an unprecedented link between lipid metabolic processes and intestinal pathologies. PMID- 26279301 TI - Ras association domain family member 10 suppresses gastric cancer growth by cooperating with GSTP1 to regulate JNK/c-Jun/AP-1 pathway. AB - The Ras association domain family (RASSF) encodes several members with tumor suppressive potentials. We aimed to investigate the biological function and clinical implication of RASSF10 in gastric cancer (GC). We found that RASSF10 was silenced in six of seven GC cell lines and in primary GC tissues, but was highly expressed in normal gastric tissues. The silence of RASSAF10 was mediated by promoter methylation as evaluated by bisulfite genomic sequencing. RASSF10 expression could be restored by demethylation treatment. A negative correlation between methylation and mRNA expression of RASSF10 was observed in 223 gastric samples of The Cancer Genome Atlas study (P<0.0001). Re-expression of RASSF10 in GC cell lines (AGS and MKN45) significantly suppressed cell viability, colony formation, migration and invasion, reduced cells in S phase, accumulated cells in G2 phase and induced cell apoptosis in vitro, and inhibited tumorigenicity in nude mice. These were confirmed by decreased expression of proliferation markers (proliferating cell nuclear antigen, p-CDC2 and p-CDC25) and increased apoptotic cascades (cleaved caspases-9, -8, -3 and cleaved poly (ADP-ribose) polymerase). Conversely, RASSF10 knockdown in normal gastric cell line yielded an opposing effect. Co-immunoprecipitation combined with mass spectrometry analyses were performed to reveal the downstream effectors of RASSF10. The result revealed that glutathione S-transferase Pi 1 (GSTP1) was a direct cooperator of RASSF10. The tumor-suppressive effect of RASSF10 was partially mediated by cooperating with GSTP1 to deregulate Jun N-terminal kinase (JNK)/c-Jun/AP-1 pathway. Importantly, RASSF10 methylation was detected in 56.6% (98/173) of primary GCs and is an independent risk factor for poor survival of GC patients (P=0.001). In conclusions, RASSF10 functions as a tumor suppressor by cooperating with GSTP1 to deregulate JNK/c-Jun/AP-1 pathway in GC. Promoter methylation of RASSF10 is associated with poor survival of GC patients. PMID- 26279302 TI - Lunatic Fringe is a potent tumor suppressor in Kras-initiated pancreatic cancer. AB - Notch controls pancreatic differentiation during development and is reactivated in pancreatic cancer. In recent years, the importance of Notch signaling in pancreatic tumorigenesis has become increasingly evident; however, it remains unclear how Notch activities are regulated in this context. Here we report differential regulation of Notch receptors by Lunatic Fringe (Lfng), which encodes an O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase known to modify epidermal growth factor repeats in the Notch extracellular domain, during pathogenesis of Kras-induced pancreatic ductal adenocarcinoma (PDAC). We show that Lfng is uniquely expressed in a subset of acinar cells in the adult pancreas. Deletion of Lfng in the Kras(LSL-G12D/+);Pdx1-Cre mouse model caused increased activation of Notch3 throughout PDAC initiation and progression, and Notch1 after the onset of disease, associated with marked upregulation of Notch target gene Hes1. Deletion of Lfng also resulted in accumulation of Aldh1 positive cell population. We found that loss of Lfng significantly accelerated Kras-initiated PDAC development and shortened survival of the PDAC mice. Interestingly, Lfng-deficient tumors showed a propensity for a poorly differentiated state with features of epithelial-to-mesenchymal transition. Likewise, knockdown of LFNG in human PDAC cell lines caused elevated Notch activation, associated with either accelerated cell proliferation or expanded Aldh1-positive cell population. Deletion of Lfng resulted in downregulation of Tgfb1, Tgfb2 and Tgfbr2 expression in the wild-type pancreas at all ages examined, and in the Kras(LSL-G12D/+);Pdx1-Cre pancreas after PDAC onset, as well as reduced phospho-Smad2 levels in pancreatic tumors. We provide evidence that Lfng regulates transforming growth factor (TGF)-beta signaling through Notch mediated transcriptional repression of TGF-beta pathway genes. Taken together, our results reveal a potent tumor-suppressive function for Lfng and crosstalk between Notch and TGF-beta pathways in the pancreas, which provides new insight into initiation of PDAC and signals involved in disease progression. PMID- 26279303 TI - PTEN activation through K163 acetylation by inhibiting HDAC6 contributes to tumour inhibition. AB - Phosphatase and tensin homologue deleted on chromosome 10 (PTEN), an important tumour-suppressor gene, is mutated, downregulated or dysfunctional in many tumours. The phosphatase activity of PTEN depends on membrane translocation (activation). As promising anti-cancer agents, histone deacetylase (HDAC) inhibitors, particularly trichostatin A (TSA), can promote PTEN membrane translocation, but the underlying mechanism remains unknown. In this study, we revealed that non-selective HDAC inhibitors, namely, TSA or suberoylanilide hydroxamic acid (SAHA), induced PTEN membrane translocation through PTEN acetylation at K163 by inhibiting HDAC6. K163 acetylation inhibited the interaction of the PTEN C-tail with the remaining part of PTEN, resulting in PTEN membrane translocation. Overexpression of wild-type PTEN, but not K163-mutated PTEN, facilitated the inhibition of cell proliferation, migration and invasion, as well as xenograft tumour growth, induced by SAHA or tubastatin A, an HDAC6 specific inhibitor. These results indicated that PTEN activation by inhibiting HDAC6 significantly contributed to tumour inhibition. Therefore, non-selective HDAC or HDAC6-specific inhibitors may be more clinically suitable to treat tumours without PTEN mutations or deletions. PMID- 26279305 TI - Fullerene-Structured MoSe2 Hollow Spheres Anchored on Highly Nitrogen-Doped Graphene as a Conductive Catalyst for Photovoltaic Applications. AB - A conductive catalyst composed of fullerene-structured MoSe2 hollow spheres and highly nitrogen-doped graphene (HNG-MoSe2) was successfully synthesized via a wet chemical process. The small molecule diethylenetriamine, which was used during the process, served as a surfactant to stabilize the fullerene-structured MoSe2 hollow spheres and to provide a high content of nitrogen heteroatoms for graphene doping (ca. 12% N). The superior synergistic effect between the highly nitrogen doped graphene and the high surface-to-volume ratio MoSe2 hollow spheres afforded the HNG-MoSe2 composite high conductivity and excellent catalytic activity as demonstrated by cyclic voltammetry, electrochemical impedance spectroscopy and Tafel measurements. A dye-sensitized solar cell (DSSC) prepared with HNG-MoSe2 as a counter electrode exhibited a conversion efficiency of 10.01%, which was close to that of a DSSC with a Pt counter electrode (10.55%). The synergy between the composite materials and the resulting highly efficient catalysis provide benchmarks for preparing well-defined, graphene-based conductive catalysts for clean and sustainable energy production. PMID- 26279304 TI - Oncoprotein ZNF322A transcriptionally deregulates alpha-adducin, cyclin D1 and p53 to promote tumor growth and metastasis in lung cancer. AB - ZNF322A encoding a classical Cys2His2 zinc finger transcription factor was previously revealed as a potential oncogene in lung cancer patients. However, the oncogenic role of ZNF322A and its underlying mechanism in lung tumorigenesis remain elusive. Here we show ZNF322A protein overexpression in 123 Asian and 74 Caucasian lung cancer patients. Multivariate Cox regression analysis indicated that ZNF322A was an independent risk factor for a poor outcome in lung cancer, corroborating the Kaplan-Meier results that patients with ZNF322A protein overexpression had significantly poorer overall survival than other patients. Overexpression of ZNF322A promoted cell proliferation and soft agar growth by prolonging cell cycle in S phase in multiple lung cell lines, including the immortalized lung cell BEAS-2B. In addition, ZNF322A overexpression enhanced cell migration and invasion, whereas knockdown of ZNF322A reduced cell growth, invasion and metastasis abilities in vitro and in vivo. Quantitative proteomic analysis revealed potential ZNF322A-regulated downstream targets, including alpha adducin (ADD1), cyclin D1 (CCND1), and p53. Using luciferase promoter activity assay combined with site-directed mutagenesis and sequential chromatin immunoprecipitation-PCR assay, we found that ZNF322A could form a complex with c Jun and cooperatively activate ADD1 and CCND1 but repress p53 gene transcription by recruiting differential chromatin modifiers, such as histone deacetylase 3, in an AP-1 element dependent manner. Reconstitution experiments indicated that CCND1 and p53 were important to ZNF322A-mediated promotion of cell proliferation, whereas ADD1 was necessary for ZNF322A-mediated cell migration and invasion. Our results provide compelling evidence that ZNF322A overexpression transcriptionally dysregulates genes involved in cell growth and motility therefore contributes to lung tumorigenesis and poor prognosis. PMID- 26279306 TI - BCR-ABL Mutations in Chronic Myeloid Leukemia Treated With Tyrosine Kinase Inhibitors and Impact on Survival. AB - This is the largest Latin American study of BCR-ABL mutations in chronic myeloid leukemia (CML) patients, resistant to imatinib (IM). In 195/467 (41%) patients, mutations were detected. The most frequent mutation was T315I (n = 31, 16%). Progression-free (PFS) and overall survival (OS) at 5 years were lower in patients with BCR-ABL mutations (43% vs. 65%, p = 0.07 and 47% vs. 72%, p = 0.03, respectively) and in those with the T315I mutation (p = 0.003 and p = 0.03). OS and PFS were superior in subgroup who switched to second generation inhibitors (SGIs) after IM failure (OS: 50% vs. 39% p = 0.01; PFS: 48% vs. 30% p = 0.02). BCR-ABL mutations conferred a significant poor prognosis in CML patients. PMID- 26279307 TI - Development of PD-1/PD-L1 Pathway in Tumor Immune Microenvironment and Treatment for Non-Small Cell Lung Cancer. AB - Lung cancer is currently the leading cause of cancer-related death in worldwide, non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. Surgery, platinum-based chemotherapy, molecular targeted agents and radiotherapy are the main treatment of NSCLC. With the strategies of treatment constantly improving, the prognosis of NSCLC patients is not as good as before, new sort of treatments are needed to be exploited. Programmed death 1 (PD-1) and its ligand PD-L1 play a key role in tumor immune escape and the formation of tumor microenvironment, closely related with tumor generation and development. Blockading the PD-1/PD-L1 pathway could reverse the tumor microenvironment and enhance the endogenous antitumor immune responses. Utilizing the PD-1 and/or PD L1 inhibitors has shown benefits in clinical trials of NSCLC. In this review, we discuss the basic principle of PD-1/PD-L1 pathway and its role in the tumorigenesis and development of NSCLC. The clinical development of PD-1/PD-L1 pathway inhibitors and the main problems in the present studies and the research direction in the future will also be discussed. PMID- 26279308 TI - Disparities in attention to HIV-prevention information. AB - Compared to European-Americans, African-Americans have greater probability of becoming infected with HIV, as well as worse outcomes when they become infected. Therefore, adequate health communications should ensure that they capture the attention of African-Americans and do not perpetuate disadvantages relative to European-Americans. The objective of this report was to examine if racial disparities in attention to health information parallel racial disparities in health outcomes. Participants were clients of a public health clinic (Study 1 n = 64; Study 2 n = 55). Unobtrusive observation in a public health waiting room, message reading times, and response-time on a modified flanker task were used to examine attention to HIV- and flu-information across racial groups. In Study 1, participants were observed for the duration of their time in a public health clinic waiting room (average duration: 31 min). In Study 2, participants completed tasks in a private room at the public health clinic (average duration: 21 min). Across all attention measures, results suggest an interaction between race and information type on attention to health information. In particular, African-Americans differentially attended to information as a function of information type, with decreased attention to HIV- versus flu-information. In contrast, European-Americans attended equally to both HIV- and flu-information. As such, disparities in attention yielded less access to certain health information for African- than European-Americans in a health setting. The identified disparities in attention are particularly problematic because they disadvantage African-Americans at a time of great effort to correct racial disparities. Modifying the framing of health information in ways that ensure attention by all racial groups may be a strategy to increase attention, and thereby reduce disparities in health outcomes. Future research should find solutions that increase attentional access to health communications for all groups. PMID- 26279309 TI - Assessing hippocampal development and language in early childhood: Evidence from a new application of the Automatic Segmentation Adapter Tool. AB - Volumetric assessments of the hippocampus and other brain structures during childhood provide useful indices of brain development and correlates of cognitive functioning in typically and atypically developing children. Automated methods such as FreeSurfer promise efficient and replicable segmentation, but may include errors which are avoided by trained manual tracers. A recently devised automated correction tool that uses a machine learning algorithm to remove systematic errors, the Automatic Segmentation Adapter Tool (ASAT), was capable of substantially improving the accuracy of FreeSurfer segmentations in an adult sample [Wang et al., 2011], but the utility of ASAT has not been examined in pediatric samples. In Study 1, the validity of FreeSurfer and ASAT corrected hippocampal segmentations were examined in 20 typically developing children and 20 children with autism spectrum disorder aged 2 and 3 years. We showed that while neither FreeSurfer nor ASAT accuracy differed by disorder or age, the accuracy of ASAT corrected segmentations were substantially better than FreeSurfer segmentations in every case, using as few as 10 training examples. In Study 2, we applied ASAT to 89 typically developing children aged 2 to 4 years to examine relations between hippocampal volume, age, sex, and expressive language. Girls had smaller hippocampi overall, and in left hippocampus this difference was larger in older than younger girls. Expressive language ability was greater in older children, and this difference was larger in those with larger hippocampi, bilaterally. Overall, this research shows that ASAT is highly reliable and useful to examinations relating behavior to hippocampal structure. PMID- 26279310 TI - Herd-level bovine tuberculosis risk factors: assessing the role of low-level badger population disturbance. AB - Bovine TB (bTB) is endemic in Irish cattle and has eluded eradication despite considerable expenditure, amid debate over the relative roles of badgers and cattle in disease transmission. Using a comprehensive dataset from Northern Ireland (>10,000 km(2); 29,513 cattle herds), we investigated interactions between host populations in one of the first large-scale risk factor analyses for new herd breakdowns to combine data on both species. Cattle risk factors (movements, international imports, bTB history, neighbours with bTB) were more strongly associated with herd risk than area-level measures of badger social group density, habitat suitability or persecution (sett disturbance). Highest risks were in areas of high badger social group density and high rates of persecution, potentially representing both responsive persecution of badgers in high cattle risk areas and effects of persecution on cattle bTB risk through badger social group disruption. Average badger persecution was associated with reduced cattle bTB risk (compared with high persecution areas), so persecution may contribute towards sustaining bTB hotspots; findings with important implications for existing and planned disease control programmes. PMID- 26279311 TI - Review of the importance of nutrition during the first 1000 days: maternal nutritional status and its associations with fetal growth and birth, neonatal and infant outcomes among African women. AB - Maternal nutritional status (MNS) is a strong predictor of growth and development in the first 1000 days of life and may influence susceptibility to non communicable diseases in adulthood. However, the role of nutrition during this window of developmental plasticity in Africa is unclear. This paper reviews published data to address whether maternal nutrition during the first 1000 days is important for Africa, with a focus on MNS and its associations with fetal growth and birth, neonatal and infant outcomes. A systematic approach was used to search the following databases: Medline, EMBASE, Web of Science, Google Scholar, ScienceDirect, SciSearch and Cochrane Library. In all, 26 studies met the inclusion criteria for the specific objectives. MNS in Africa showed features typical of the epidemiological transition: higher prevalences of maternal overweight and obesity and lower underweight, poor diet quality 1 and high anaemia prevalence. Maternal body mass index and greater gestational weight gain (GWG) were positively associated with birth weight; however, maternal overweight and obesity were associated with increased risk of macrosomia and intrauterine growth restriction. Maternal anaemia was associated with lower birth weight. Macro- and micronutrient supplementation during pregnancy were associated with improvements in GWG, birth weight and mortality risk. Data suggest poor MNS in Africa and confirms the importance of the first 1000 days as a critical period for nutritional intervention to improve growth, birth outcomes and potential future health risk. However, there is a lack of data beyond birth and a need for longitudinal data through infancy to 2 years of age. PMID- 26279313 TI - Heart rate and heart rate variability in pregnant dairy cows and their fetuses determined by fetomaternal electrocardiography. AB - In this study, fetomaternal electrocardiograms were recorded once weekly in cattle during the last 14 weeks of gestation. From the recorded beat-to-beat (RR) intervals, heart rate and heart rate variability (HRV) variables standard deviation of the RR interval (SDRR) and root mean square of successive RR differences (RMSSD) were calculated. To differentiate between effects of lactation and gestation, pregnant lactating (PL) cows (n = 7) and pregnant nonlactating (PNL) heifers (n = 8) were included. We hypothesized that lactation is associated with stress detectable by HRV analysis. We also followed the hypothesis that heart rate and HRV are influenced by growth and maturation of the fetus toward term. Maternal heart rate changed over time in both groups, and in PL cows, it decreased with drying-off. During the last 5 weeks of gestation, maternal heart rate increased in both groups but was lower in PL cows than in PNL heifers. Maternal HRV did not change over time, but SDRR was significantly higher in PL cows than in PNL heifers, and significant interactions of group * time existed. On the basis of HRV, undisturbed pregnancies are thus no stressor for the dam in cattle. Fetal heart rate decreased from week 14 to week 1 before birth with no difference between groups. Gestational age thus determines heart rate in the bovine fetus. The HRV variables SDRR and RMSSD increased toward the end of gestation in fetuses carried by cows but not in those carried by heifers. The increase in HRV indicates maturation of fetal cardiac regulation which may be overrun by high sympathoadrenal activity in fetuses carried by heifers as suggested by their low HRV. PMID- 26279312 TI - In vitro bovine embryo production in a synthetic medium: embryo development, cryosurvival, and establishment of pregnancy. AB - The aim of this study was to develop an in vitro embryo culture medium without either fetal calf serum or BSA, using various growth factors and cytokines (GFs CYKs; IGF-I, IGF-II, bFGF, LIF, GM-CSF, TGF-beta1, and PDGF-BB), and other molecules with surfactant and embryotrophic properties, such as recombinant albumin (RA) and hyaluronan (HA). The first part of the study was dedicated to define the best combination of GFs-CYKs + RA + HA for optimal embryonic development. Next, we compared development rates and embryo quality (inner cell mass [ICM]-to-total cell number [TCN] ratio), and postthaw survival and hatching rates using this synthetic medium (T1) and a control medium: synthetic oviduct fluid + BSA + ITS (insulin, transferrin, and selenium). The blastocyst rates were significantly higher with T1 than those with the control at 7 and 8 days after fertilization. There was no significant difference in TCN or the ICM/TCN ratio between the two treatments. Survival and hatching rates 48 hours after thawing were similar for both treatments. Finally, nine embryo transfers were conducted using fresh and previously frozen Day-7 blastocysts to evaluate the in vivo viability of embryos produced in this synthetic medium; four gestations were obtained from six fresh embryos and one gestation from three frozen embryos. In conclusion, the fetal calf serum and BSA-free medium, supplemented with GFs-CYKs + RA + HA, improved embryo development and gave comparable ICM/TCN ratios and postthaw survival rates to the control with BSA. Fresh and frozen embryos produced in this medium are viable for embryo transfer. This fully synthetic method of embryo culture is a useful means of reducing the risk of disease transmission via embryo transfer. PMID- 26279315 TI - Influence of agricultural practice on mobile bla genes: IncI1-bearing CTX-M, SHV, CMY and TEM in Escherichia coli from intensive farming soils. AB - Many calls have been made to address antibiotic resistance in an environmental perspective. With this study, we showed the widespread presence of high-level antibiotic resistant isolates on a collection of non-susceptible Gram-negative bacteria (n = 232) recovered from soils. Bacteria were selected using amoxicillin, cefotaxime and imipenem, from sites representing different agricultural practices (extensive, intensive and organic). Striking levels of non susceptibility were noticed in intensive soils for norfloxacin (74%), streptomycin (50.7%) and tetracycline (46.6%); indeed, the exposure to intensive agricultural practices constituted a risk factor for non-susceptibility to many antibiotics, multidrug resistance and production of extended-spectrum beta lactamases (ESBL). Analyses of non-susceptibility highlighted that environmental and clinical bacteria from the same species might not share the same intrinsic resistance patterns, raising concerns for therapy choices in environment-borne infections. The multiple sequence-type IncI1-driven spread of penicillinases (blaTEM-1, blaTEM-135), ESBL (blaSHV-12 and blaCTX-M-1) and plasmid-mediated AmpC beta-lactamases (blaCMY-2), produced by isolates that share their molecular features with isolates from humans and animals, suggests contamination of agricultural soils. This is also the first appearance of IncI1/ST28-harbouring blaCTX-M-1, which should be monitored to prevent their establishment as successfully dispersed plasmids. This research may help disclose paths of contamination by mobile antibiotic resistance determinants and the risks for their dissemination. PMID- 26279314 TI - Histone-lysine N-methyltransferase SETDB1 is required for development of the bovine blastocyst. AB - Transcripts derived from select clades of transposable elements are among the first to appear in early mouse and human embryos, indicating transposable elements and the mechanisms that regulate their activity are fundamental to the establishment of the founding mammalian lineages. However, the mechanisms by which these parasitic sequences are involved in directing the developmental program are still poorly characterized. Transposable elements are regulated through epigenetic means, where combinatorial patterns of DNA methylation and histone 3 lysine 9 trimethylation (H3K9me3) suppress their transcription. From studies in rodents, SET domain bifurcated 1 (SETDB1) has emerged as the core methyltransferase responsible for marking transposable elements with H3K9me3 and temporally regulating their transcriptional activity. SETDB1 loss of function studies in mice reveal that although extraembryonic tissues do not require this methyltransferase, establishment of the embryo proper fails without it. As the bovine embryo initiates the processes of epigenetic programming earlier in the preimplantation phase, we sought to determine whether suppressing SETDB1 would block the formation of the inner cell mass. We report here that bovine SETDB1 transcripts are present throughout preimplantation development, and RNA interference-based depletion blocks embryo growth at the morula stage of development. Although we did not observe alterations in global histone methylation or transposable element transcription, we did observe increased global levels of H3K27 acetylation, an epigenetic mark associated with active enhancers. Our observations suggest that SETDB1 might interact with the epigenetic machinery controlling enhancer function and that suppression of this methyltransferase may disrupt the bovine developmental program. PMID- 26279316 TI - Low serum 25-hydroxyvitamin D levels and secondary hyperparathyroidism in Fontan patients. AB - BACKGROUND: Limited data exist on the vitamin D status in Fontan patients. We determined the prevalence and potential risk factors of vitamin D deficiency in this patient subset. Methods and results Data were collected from 27 Fontan patients (55.6% male, mean age 8.1+/-5.3 years). Protein-losing enteropathy was diagnosed in six patients (22.2%). Vitamin D deficiency was defined as a serum 25 hydroxyvitamin D level of <20 ng/ml. The neutrophil-to-lymphocyte ratio, a marker of systemic inflammation, was calculated. Associations between laboratory measurements and patient characteristics were explored. Mean serum 25 hydroxyvitamin D level was 14.1+/-10.4 ng/ml. Vitamin D deficiency was found in 19/27 patients (70.3%). Only skin type was associated with vitamin D deficiency (p=0.04). Hyperparathyroidism was present in 5/21 (23.8%) patients, and was more prevalent in patients with protein-losing enteropathy (p<0.001). Parathyroid hormone levels correlated with parameters of systemic inflammation (neutrophil-to lymphocyte ratio: r=0.484, p=0.026; relative lymphocyte count: r=-0.635, p=0.002). Vitamin D supplementation significantly increased serum 25 hydroxyvitamin D levels (p<0.0001), and was accompanied by a reduction in parathyroid hormone concentrations (p=0.032). CONCLUSIONS: A high prevalence of vitamin D deficiency was found among Fontan patients, independent of age, time after Fontan procedure, ventricular morphology, and presence of protein-losing enteropathy. A potentially important link between parathyroid hormone levels and systemic inflammation is suggested. PMID- 26279317 TI - Crack formation and prevention in colloidal drops. AB - Crack formation is a frequent result of residual stress release from colloidal films made by the evaporation of colloidal droplets containing nanoparticles. Crack prevention is a significant task in industrial applications such as painting and inkjet printing with colloidal nanoparticles. Here, we illustrate how colloidal drops evaporate and how crack generation is dependent on the particle size and initial volume fraction, through direct visualization of the individual colloids with confocal laser microscopy. To prevent crack formation, we suggest use of a versatile method to control the colloid-polymer interactions by mixing a nonadsorbing polymer with the colloidal suspension, which is known to drive gelation of the particles with short-range attraction. Gelation-driven crack prevention is a feasible and simple method to obtain crack-free, uniform coatings through drying-mediated assembly of colloidal nanoparticles. PMID- 26279318 TI - Midwives and information on prenatal testing with focus on Down syndrome. AB - OBJECTIVE: To investigate midwives' knowledge of prenatal diagnosis especially Down syndrome, information given by midwives to parents, expectant parents' requests for information and how midwives perceive their own competence to give information. METHOD: A cross-sectional, prospective study with a questionnaire was completed by 64 out of 70 midwives working in the outpatient antenatal care in Uppsala County, Sweden. RESULTS: The midwives had varying and in some areas low levels of knowledge about Down syndrome. Information about Down syndrome was most often given only when asked for or when there was an increased probability of a Down syndrome pregnancy. The most common questions from expectant parents concerned test methods and risk assessments while questions regarding symptoms of Down syndrome and consequences of having a child with Down syndrome were uncommon. The majority (83-89%) had insufficient or no education regarding different prenatal tests. Only two midwives (3%) had received education about Down syndrome, and 9% felt they had sufficient knowledge to inform about the syndrome. More education about prenatal tests and Down syndrome was desired by 94%. CONCLUSION: It is important to ensure that midwives in antenatal care have sufficient knowledge to inform expectant parents about the conditions screened for. (c) 2015 John Wiley & Sons, Ltd. PMID- 26279319 TI - Increased oxidative stress and apoptosis in peripheral blood mononuclear cells of fructose-fed rats. AB - BACKGROUND: Measuring of oxidative stress in peripheral blood mononuclear cells is a suitable model of dietary induced systemic oxidative stress. Thus, we aimed to evaluate whether a chronic high fructose intake could induce oxidative damage in peripheral blood and bone marrow mononuclear cells of rats. METHODS: Animals were randomly assigned to the following groups: Control group (standard rat chow and tap water n=8), and Fructose group (standard rat chow and a 10% fructose solution in the drinking water n=8). Reactive oxygen species and cytokines were measure using flow cytometry in peripheral blood and bone-marrow mononuclear cells. Apoptotic cell death and the advanced oxidation protein products (AOPP) were also determined. RESULTS: We observed a significant increase in ROS production in peripheral blood mononuclear cells of fructose group as compared to control rats. Apoptosis and the AOPP were higher in those animals underwent high fructose intake. Serum levels of IL-6 and IL-12 were also increased after 12 weeks of high fructose intake. CONCLUSION: We concluded that fructose intake leads to systemic oxidative stress and pro-inflammatory condition which affect peripheral blood mononuclear cells and bone-marrow mononuclear cells viability. PMID- 26279320 TI - Retrospective analysis of safety and efficacy of liraglutide monotherapy and sulfonylurea-combination therapy in Japanese type 2 diabetes: Association of remaining beta-cell function and achievement of HbA1c target one year after initiation. AB - AIMS: The GLP-1 receptor agonist liraglutide improves impaired pancreatic beta cell function, thereby exerting glucose-lowering effects. However, the association of remaining beta-cell function with long-term therapeutic efficacy of liraglutide remains largely unknown. METHODS: Patients with type 2 diabetes who started liraglutide as monotherapy or sulfonylurea-combination therapy were retrospectively analyzed to identify possible associations of indices related to beta-cell function including increments of C-peptide immunoreactivity in glucagon stimulation test (GST-DeltaCPR) with achievement of HbA1c <7.0% at 54weeks after liraglutide initiation. RESULTS: Among 165 subjects continuing liraglutide for 54weeks, 66 received additional oral anti-diabetic drugs (OADs) during the period. Of those continuing liraglutide without receiving additional OADs, 41 subjects achieved HbA1c <7.0% at 54weeks, while 49 subjects did not. Subjects achieving HbA1c <7.0% showed higher values of GST-DeltaCPR. Receiver-operating analysis revealed 2.34ng/mL as the cut-off value for HbA1c <7.0% achievement in these subjects. Subjects with GST-DeltaCPR >2.34ng/mL showed continuous and substantial HbA1c reduction throughout the 54weeks. In Kaplan-Meier analysis, subjects with GST-DeltaCPR >2.34ng/mL showed longer therapeutic durability of initial liraglutide therapy with no additional OADs or insulin. CONCLUSIONS: Despite numerous limitations, these results indicate that long-term efficacy of liraglutide is associated with remaining beta-cell function at initiation. PMID- 26279321 TI - The frequency and impact of hypoglycemia among hospitalized patients with diabetes: A population-based study. AB - We aimed to evaluate the frequency of hypoglycemia and its impact on the length of stay and all-cause in-hospital mortality in hospitalized patients with diabetes. We used data from the Basic Minimum Data Set of the Spanish National Health System. Hypoglycemia was defined as having an ICD-9-CM code 250.8, 251.0, 251.1, and 251.2, and categorized as primary if it was the main cause of admission and secondary if it occurred during the hospital stay. The association between hypoglycemia and the study outcomes was evaluated in two cohorts - with and without secondary hypoglycemia - matched by propensity scores and using multivariate models. Among the 5,447,725 discharges with a diagnosis of diabetes recorded from January 1997 to December 2010, there were 92,591 (1.7%) discharges with primary hypoglycemia and 154,510 (2.8%) with secondary hypoglycemia. The prevalence of secondary hypoglycemia increased from 1.1% in 1997 to a peak of 3.8% in 2007, while the prevalence of primary hypoglycemia remained fairly stable. Primary hypoglycemia was associated with reduced in-hospital mortality (Odds ratio [OR] 0.06; 95% Confidence interval [CI], 0.03-0.10) and a significant decrease in time to discharge (Hazard ratio [HR] 2.53; 95% CI, 2.30-2.76), while secondary hypoglycemia was associated with an increased likelihood of in-hospital mortality (OR 1.12; 95% CI, 1.09-1.15) and a significant increase in time to discharge (HR 0.80; 95% CI, 0.79-0.80). In conclusion, the prevalence of secondary hypoglycemia is increasing in patients with diabetes and is associated with an increased likelihood of in-hospital mortality and a longer hospital stay. PMID- 26279322 TI - Vocal Tract Discomfort and Risk Factors in University Teachers. AB - OBJECTIVES: To characterize the presence of and risk factors for throat pain or irritation among male and female university teachers in private institutions within the city of Sao Paulo. STUDY DESIGN: This is a cross-sectional survey. METHODS: Voice self-evaluation forms prepared by the Brazilian Ministry of Labor were administered to 846 university teachers in a private institution in the city of Sao Paulo, Brazil. RESULTS: The prevalence of throat pain or irritation was 50.8% and was higher in the women (62.7%) than in the men (43.5%). The prevalence of throat pain or irritation was higher among professionals <=60 years old and among those who spent most of their time teaching compared with those who spent most of their time performing other professional activities. Other factors, such as noise and sound competition, air pollution, stress and anxiety, personal habits, and lifestyle/quality of life, were related to the presence of throat pain or irritation. CONCLUSIONS: University teachers demonstrated a high prevalence of throat pain or irritation. Factors such as age <=60 years, female gender, time-consuming professional activities, noise and sound competition in the work environment, stress and anxiety, air pollution, access to water, personal habits, and lifestyle/quality of life were related to the presence of throat pain or irritation. PMID- 26279323 TI - Early-Stage Classic Hodgkin Lymphoma: The Utilization of Radiation Therapy and Its Impact on Overall Survival. AB - PURPOSE: To examine the association between radiation therapy (RT) utilization and overall survival (OS) for patients with early-stage Hodgkin lymphoma (HL). METHODS AND MATERIALS: Using the National Cancer Database, we evaluated clinical features and survival outcomes among patients diagnosed with stage I/II HL from 1998 to 2011. The association between RT use, covariables, and outcome was assessed in a Cox proportional hazards regression model. Propensity score matching was performed to balance observed confounding factors. Survival was estimated using the Kaplan-Meier method. RESULTS: Among the 41,943 patients in the National Cancer Database with stage I/II HL, 29,752 patients were analyzed for this study. Radiation therapy use was associated with younger age (<=40 years), favorable insured status, higher socioeconomic status (income, education), and treatment at comprehensive community cancer centers (all P<.05). Five-year OS for patients receiving RT was 94.5%, versus 88.9% for those not receiving RT (P<.01). Radiation therapy use was a significant predictor of OS in the "As-Treated" cohort (hazard ratio 0.53, 95% confidence interval 0.49-0.58, P<.01) and intention-to-treat analysis (P<.01). After propensity score matching based on clinicopathologic characteristics, RT use remained associated with improved OS (hazard ratio 0.46, 95% confidence interval 0.38-0.56, P<.01). Over the study period, RT utilization for this cohort decreased from 55% to 44%, most commonly because it was not part of the planned initial treatment strategy. CONCLUSIONS: Consolidation RT was associated with improved OS for patients with early-stage classic HL. We also have identified patient-specific variations in the use of RT that may be targeted to improve patient access to care. PMID- 26279324 TI - Adverse Outcomes After Palliative Radiation Therapy for Uncomplicated Spine Metastases: Role of Spinal Instability and Single-Fraction Radiation Therapy. AB - PURPOSE: Level I evidence demonstrates equivalent pain response after single fraction (SF) or multifraction (MF) radiation therapy (RT) for bone metastases. The purpose of this study is to provide additional data to inform the incidence and predictors of adverse outcomes after RT for spine metastases. METHODS AND MATERIALS: At a single institution, 299 uncomplicated spine metastases (without cord compression, prior RT, or surgery) treated with RT from 2008 to 2013 were retrospectively reviewed. The spinal instability neoplastic score (SINS) was used to assess spinal instability. The primary outcome was time to first spinal adverse event (SAE) at the site, including symptomatic vertebral fracture, hospitalization for site-related pain, salvage surgery, interventional procedure, new neurologic symptoms, or cord compression. Fine and Gray's multivariable model assessed associations of the primary outcome with SINS, SF RT, and other significant baseline factors. Propensity score matched analysis further assessed the relationship of SF RT to first SAEs. RESULTS: The cumulative incidence of first SAE after SF RT (n=66) was 6.8% at 30 days, 16.9% at 90 days, and 23.6% at 180 days. For MF RT (n=233), the incidence was 3.5%, 6.4%, and 9.2%, respectively. In multivariable analysis, SF RT (hazard ratio [HR] = 2.8, 95% confidence interval [CI] 1.5-5.2, P=.001) and SINS >= 11 (HR=2.5 , 95% CI 1.3 4.9, P=.007) were predictors of the incidence of first SAE. In propensity score matched analysis, first SAEs had developed in 22% of patients with SF RT versus 6% of those with MF RT cases (HR=3.9, 95% CI 1.6-9.6, P=.003) at 90 days after RT. CONCLUSION: In uncomplicated spinal metastases treated with RT alone, spinal instability with SINS >= 11 and SF RT were associated with a higher rate of SAEs. PMID- 26279325 TI - Myeloperoxidase Inhibitors as Potential Drugs. AB - Myeloperoxidase (MPO) is an important member of the haem peroxidase - cyclooxygenase superfamily. This enzyme is physiologically expressed in circulating neutrophils, monocytes and some tissue macrophages including microglia. MPO plays an essential role in the antimicrobial and antiviral system of humans. The microbicidal activity of MPO exists due to its capability to oxidize halide and pseudohalide ions (CI(-), Br(-), I(-) and SCN(-)) by H2O2, thereby producing respective hypohalous acids (HOX). During the phagocytosis of pathogens, azurophilic granules release their content together with MPO into phagolysosomes. On the other hand, MPO can be discharged outside the phagocytes. Due to this, tissue damage during inflammation is greatly promoted by MPO-derived oxidants. Regarding its activity, MPO is a key factor in a great number of conditions within the group of cardiovascular diseases, inflammatory diseases, neurodegenerative diseases, kidney diseases and immune-mediated diseases. Therefore, MPO and its downstream inflammatory pathways might be attractive targets for both prognostic and therapeutic intervention in the prophylaxis of all mentioned illnesses. Nowadays, structure and reaction mechanism of MPO are known, which enable rational strategy in the development of specific MPO inhibitors that still preserve MPO activity during host defense from bacteria, but hinder pathophysiologically persistent activation of MPO. Various methods for MPO activity inhibition and unfavorable effects of MPO-derived oxidants remodeling will be discussed. Emphasis will be put on various known inhibitors, as well as on newly investigated natural products, which can also inhibit MPO activity. PMID- 26279326 TI - Applications of Metabonomics in Pesticide Toxicology. AB - Metabonomic studies quantitatively measure the small molecule metabolites and their intermediates in the biological samples (serum, urine or tissue extracts) and have gained wide applications in many fields, especially in toxicology. Pesticides are extensively used around the world and pesticide toxicity has become a serious threat to human health. Metabonomic approach has been applied in many aspects of pesticide toxicology research such as eco-environmental toxicity studies, biomarker identification, and mechanism of toxicity studies. Both whole organism animal models and cell culture models are used for metabonomic studies on pesticide toxicology. In the literature, metabonomic analyses on the toxicity of over thirty common pesticides, including insecticides, herbicides and fungicides, have been carried out using magnetic resonance spectroscopy or mass spectrometry. The combined toxicity of pesticides or pesticide with heavy metals was also investigated with metabonomic approach. In this article, recent progresses made in applying metabonomic approach in pesticide toxicology are thoroughly reviewed and the challenges with application of this approach are also discussed. PMID- 26279327 TI - Lipid-Based Formulations for Oral Drug Delivery: Effects on Drug Absorption and Metabolism. AB - The application of lipid-based drug delivery systems on the industrial scale has successfully demonstrated their therapeutic and manufacturing advantages. Recently, various lipid-based formulations were successfully prepared for oral delivery of compounds that are difficult to administer. Nevertheless, an improved understanding of how these formulations affect drug absorption and metabolism is required to support the rapid and successful completion of drug development programs. In this review, we report the detailed mechanisms whereby lipids and lipid-based excipients affect drug absorption and metabolism, and summarize the capacity of lipids and lipid-based formulations to improve drug absorption by improving drug solubility, mucosa penetration, lymphatic transport, and hepatic metabolism. Finally, we discuss the progress made toward the use of novel lipid formulations to enhance oral absorption by surmounting specific absorption barriers. PMID- 26279328 TI - Submicron Lipid Emulsions: A Versatile Platform for Drug Delivery. AB - Lipid emulsions have turned out to be a versatile tool for systemic delivery of poorly soluble drugs and cytotoxic drugs. Currently, the majority of marketed or developing drugs are recognized as BCS II and IV ones. How to solve the solubility and systemic administration that enables them access to clinical application is arising a great challenge in drug delivery systems. The key considerations for lipid emulsions are how to enhance the drug load, stability and reproducibility. Formulation and manufacture technique play the leading role in development of lipid emulsions. Understanding the biofate and characterization in vitro/vivo is suggestive to exploit the potential of lipid emulsions. This review discussed the manufacture techniques and in vivo behavior of lipid emulsions. Momentous interests were focused on their applications in drug delivery as well as the future evolution. Finally, we appreciated the methodologies of quality control and systemic risks associated with lipid emulsions. PMID- 26279330 TI - Callosal disconnection syndrome in symptomatic female carrier of Pelizaeus Merzbacher disease. PMID- 26279331 TI - Neuroprotective effect of nicorandil through inhibition of apoptosis by the PI3K/Akt1 pathway in a mouse model of deep hypothermic low flow. AB - OBJECTIVE: Nicorandil exerts a protective effect on ischemia-reperfusion (I/R) injury in the brain and kidney through anti-apoptotic mechanisms. However, the mechanism by which nicorandil protects against I/R injury induced by deep hypothermic low flow (DHLF) remains unclear. METHODS: We used a cerebral I/R model induced by DHLF to determine the neuroprotective effects and possible mechanisms of nicorandil. RESULTS: Hematoxylin-eosin (HE) staining and in situ terminal deoxynucleotidyl transferase UTP nick end labeling (TUNEL) assay were used to detect changes in cell morphology and the number of apoptotic cells in hippocampus, respectively. The apoptotic regulators including Bcl-2, Bax, Akt, and p-Akt (the active, phosphorylated form of Akt) were examined by Western blot (WB). Histopathological findings showed that nicorandil significantly alleviated morphological damage in hippocampal and reduced the number of TUNEL-positive nuclei induced by DHLF. Nicorandil also increased the expression of Bcl-2 and decreased the expression of Bax, while increasing p-Akt level. Consistent with these results, nicorandil-mediated neuroprotection was reduced in the Akt1+/- mutant mice and inhibited by LY294002, a PI3K inhibitor. CONCLUSIONS: These findings showed that nicorandil provides a neuroprotective role in DHLF-induced I/R injury by inhibiting apoptosis via activation of the PI3K/Akt1 signaling pathway. PMID- 26279332 TI - Pitfalls in the diagnosis of leprous neuropathy: lessons learnt from a University hospital in an endemic zone. PMID- 26279333 TI - Long-term enzyme-replacement therapy (ERT) with alglucosidase alfa: Evolution of two siblings with juvenile late-onset Pompe disease. PMID- 26279334 TI - Iranian nursing students' preparedness for clinical training: A qualitative study. AB - BACKGROUND: Clinical training plays a fundamental role in nursing students' acquisition of professional capabilities. Students' preparedness for learning in clinical setting is one of the most important factors that determine the quality of clinical training. Different studies indicate the nursing students' unpreparedness for entering clinical environment. AIM: The aim of this study was to explore Iranian nursing students' preparedness for clinical training. METHOD: This research is a qualitative research using content analysis approach. The participants consisted of seventeen nursing students, three nursing educators and one nurse, selected through the purposive sampling method and questioned in semi structured interviews. The acquired data was analyzed by qualitative content analysis approach. RESULTS: Two main themes were captured in this study; including: 1) rejection of the profession and 2) fear and anxiety CONCLUSION: The findings indicated that the nursing students are not psychologically prepared for internship in clinical settings. Therefore we recommend in the first place reducing students' fear and anxiety of facing the reality and preparing them for a better beginning through conducting workshops in retraining and practicing clinical skills along with a course of visiting the hospital for students' confrontation and familiarization with real environment immediately before entering into the clinical setting. In addition, after the students' entrance to the setting the clinical educators should strive to heed students' level of preparedness especially their psychological needs and condition including the extent to which they accept their profession. PMID- 26279335 TI - Characteristics and values of a British military nurse. International implications of War Zone qualitative research. AB - BACKGROUND: Between 2001 and 2014, British military nurses served in Afghanistan caring for both Service personnel and local nationals of all ages. However, there have been few research studies assessing the effectiveness of the military nurses' operational role and no papers naming the core values and characteristics. This paper is from the only qualitative nursing study completed during this period where data was collected in the War Zone. OBJECTIVE: To explore the characteristics and values that are intrinsic to military nurses in undertaking their operational role. DESIGN: A constructivist grounded theory was utilised. The authors designed the interview schedule, and then following a pilot study, conducted and transcribed the discussions. Informed consent and UK Ministry of Defence Research Ethical Committee approval was obtained. SETTING: Camp Bastion Hospital, Afghanistan, in 2013. METHOD: Semi-structured interviews were conducted with 18 British Armed Forces nurses. RESULTS: A theoretical model was developed that identifies the intrinsic characteristics and values required to be a military nurse. Nursing care delivered within the operational environment was perceived as outstanding. Nurses consciously detached themselves from any legal processes and treated each casualty as a vulnerable patient, resulting in care, compassion and dignity being provided for all patients, irrespective of their background, beliefs or affiliations. CONCLUSION: The study findings provide military nurses with a framework for a realistic personal development plan that will allow them to build upon their strengths as well as to identify and ameliorate potential areas of weakness. Placing nurses first, with a model that focusses on the requirements of a good nurse has the potential to lead to better patient care, and improve the quality of the tour for defence nurses. These findings have international implications and have the potential for transferability to any level of military or civilian nursing practice. PMID- 26279336 TI - Using Facebook to enhance commencing student confidence in clinical skill development: A phenomenological hermeneutic study. AB - AIM: The purpose of this study was to explore commencing nursing students' experience of Facebook as an adjunct to on-campus course delivery to determine its impact as a learning strategy for improving confidence in clinical skill development. BACKGROUND: Approaches supporting nursing students in the development of clinical skills have relied on 'real-life' clinical placements and simulated on-campus clinical laboratories. However students continue to report a lack of confidence in their clinical skills for practice. Social networking sites including Facebook are being used as a learning strategy to stimulate active and collaborative learning approaches. DESIGN: A hermeneutic phenomenological approach was used to provide an understanding of the experience of confidence in clinical skills development for nursing students. METHODS: Data were collected through in-depth interviews with commencing students about their experience as learners using Facebook and their perceptions of the impact on their clinical skill development. SETTINGS AND PARTICIPANTS: Ten first-year student nurses at one university in south-east Queensland, Australia. FINDINGS: Four themes emerged from the data including: 'We're all in this together'; 'I can do this'; 'This is about my future goals and success'; and, 'Real time is not fast enough!'. These themes provide new meaningful insights demonstrating students' sense of confidence in clinical skills was increased through engagement with a dedicated Facebook page. CONCLUSIONS: The findings of this study have relevance to academics in the design of learning strategies for clinical courses to further support student confidence and engagement through peer collaboration and active learning processes. PMID- 26279337 TI - Gender Specific Association between Serum Fibroblast Growth Factor 23/alpha Klotho and Coronary Artery and Aortic Valve Calcification. AB - AIM: Fibroblast growth factor 23 (FGF23) and alpha-Klotho have been recently identified to play a crucial role in calcium/phosphate metabolism. We herein investigated the possible relation between serum FGF23/alpha-Klotho levels and coronary artery calcification (CAC) and aortic valve calcification (AVC). METHODS: Among subjects with diagnosed or suspected coronary artery disease (CAD), CAC and AVC were estimated via the Agatston score of 320-detector computed tomography images, and serum FGF23 and alpha-Klotho levels were measured. RESULTS: In total, 157 subjects were enrolled (75 women and 82 men). We performed logistic regression using CAC as a dependent variable; the highest FGF23 tertile (> 52.5 pg/mL) was significantly positively associated with CAC with an odds ratio of 6.61 versus the lowest FGF23 tertile (< 35.3 pg/mL) in women after the adjustment for potential confounding variables including age, renal function, hypertension, statin use, diuretic use, and calcium/phosphate metabolism related factors. In addition, the highest alpha-Klotho tertile (> 561 pg/mL) was significantly associated with AVC with an odds ratio of 6.31 versus the lowest alpha-Klotho tertile (< 306 pg/mL) in men after adjusting for the same variables. On the other hand, the association between FGF23 and CAC/AVC in men or that between alpha-Klotho and CAC/AVC in women was nonsignificant. CONCLUSION: Among subjects with diagnosed or suspected CAD, serum FGF23 was positively associated with CAC in women and serum alpha-Klotho was positively associated with AVC in men independent of the confounding variables, including the renal function and calcium/phosphate metabolism-related factors. PMID- 26279338 TI - Development of an APC-targeted multivalent E2-based vaccine against Bovine Viral Diarrhea Virus types 1 and 2. AB - The aim of this study was to develop and test a multivalent subunit vaccine against Bovine Viral Diarrhea Virus (BVDV) based on the E2 virus glycoprotein belonging to genotypes 1a, 1b and 2a, immunopotentiated by targeting these antigens to antigen-presenting cells. The E2 antigens were expressed in insect cells by a baculovirus vector as fusion proteins with a single chain antibody, named APCH I, which recognizes the beta-chain of the MHC Class II antigen. The three chimeric proteins were evaluated for their immunogenicity in a guinea pig model as well as in colostrum-deprived calves. Once the immune response in experimentally vaccinated calves was evaluated, immunized animals were challenged with type 1b or type 2b BVDV in order to study the protection conferred by the experimental vaccine. The recombinant APCH I-tE21a-1b-2a vaccine was immunogenic both in guinea pigs and calves, inducing neutralizing antibodies. After BVDV type 1b and type 2 challenge of vaccinated calves in a proof of concept, the type 1b virus could not be isolated in any animal; meanwhile it was detected in all challenged non-vaccinated control animals. However, the type 2 BVDV was isolated to a lesser extent compared to unvaccinated animals challenged with type 2 BVDV. Clinical signs associated to BVDV, hyperthermia and leukopenia were reduced with respect to controls in all vaccinated calves. Given these results, this multivalent vaccine holds promise for a safe and effective tool to control BVDV in herds. PMID- 26279339 TI - Lot-to-lot consistency of a tetravalent dengue vaccine in healthy adults in Australia: a randomised study. AB - BACKGROUND: The recombinant yellow fever-17D-dengue virus, live, attenuated, tetravalent dengue vaccine (CYD-TDV) has undergone extensive clinical trials. Here safety and consistency of immunogenicity of phase III manufacturing lots of CYD-TDV were evaluated and compared with a phase II lot and placebo in a dengue naive population. METHODS: Healthy 18-60 year-olds were randomly assigned in a 3:3:3:3:1 ratio to receive three subcutaneous doses of either CYD-TDV from any one of three phase III lots or a phase II lot, or placebo, respectively in a 0, 6, 12 month dosing schedule. Neutralising antibody geometric mean titres (PRNT50 GMTs) for each of the four dengue serotypes were compared in sera collected 28 days after the third vaccination-equivalence among lots was demonstrated if the lower and upper limits of the two-sided 95% CIs of the GMT ratio were >=0.5 and <=2.0, respectively. RESULTS: 712 participants received vaccine or placebo and 614 (86%) completed the study; 17 (2.4%) participants withdrew after adverse events. Equivalence of phase III lots was demonstrated for 11 of 12 pairwise comparisons. One of three comparisons for serotype 2 was not statistically equivalent. GMTs for serotype 2 in phase III lots were close to each other (65.9, 44.1 and 58.1, respectively). CONCLUSIONS: Phase III lots can be produced in a consistent manner with predictable immune response and acceptable safety profile similar to previously characterised phase II lots. The phase III lots may be considered as not clinically different as statistical equivalence was shown for serotypes 1, 3 and 4 across the phase III lots. For serotype 2, although equivalence was not shown between two lots, the GMTs observed in the phase III lots were consistently higher than those for the phase II lot. As such, in our view, biological equivalence for all serotypes was demonstrated. PMID- 26279340 TI - An Intron 9 CYP19 Gene Variant (IVS9+5G>A), Present in an Aromatase-Deficient Girl, Affects Normal Splicing and Is Also Present in Normal Human Steroidogenic Tissues. AB - BACKGROUND/AIMS: Splicing CYP19 gene variants causing aromatase deficiency in 46,XX disorder of sexual development (DSD) patients have been reported in a few cases. A misbalance between normal and aberrant splicing variants was proposed to explain spontaneous pubertal breast development but an incomplete sex maturation progress. The aim of this study was to functionally characterize a novel CYP19A1 intronic homozygote mutation (IVS9+5G>A) in a 46,XX DSD girl presenting spontaneous breast development and primary amenorrhea, and to evaluate similar splicing variant expression in normal steroidogenic tissues. METHODS: Genomic DNA analysis, splicing prediction programs, splicing assays, and in vitro protein expression and enzyme activity analyses were carried out. CYP19A1 mRNA expression in human steroidogenic tissues was also studied. RESULTS: A novel IVS9+5G>A homozygote mutation was found. In silico analysis predicts the disappearance of the splicing donor site in intron 9, confirmed by patient peripheral leukocyte cP450arom and in vitro studies. Protein analysis showed a shorter and inactive protein. The intron 9 transcript variant was also found in human steroidogenic tissues. CONCLUSIONS: The mutation IVS9+5G>A generates a splicing variant that includes intron 9 which is also present in normal human steroidogenic tissues, suggesting that a misbalance between normal and aberrant splicing variants might occur in target tissues, explaining the clinical phenotype in the affected patient. PMID- 26279341 TI - Automatic segmentation of the lateral geniculate nucleus: Application to control and glaucoma patients. AB - BACKGROUND: The lateral geniculate nucleus (LGN) is a key relay center of the visual system. Because the LGN morphology is affected by different diseases, it is of interest to analyze its morphology by segmentation. However, existing LGN segmentation methods are non-automatic, inefficient and prone to experimenters' bias. NEW METHOD: To address these problems, we proposed an automatic LGN segmentation algorithm based on T1-weighted imaging. First, the prior information of LGN was used to create a prior mask. Then region growing was applied to delineate LGN. We evaluated this automatic LGN segmentation method by (1) comparison with manually segmented LGN, (2) anatomically locating LGN in the visual system via LGN-based tractography, (3) application to control and glaucoma patients. RESULTS: The similarity coefficients of automatic segmented LGN and manually segmented one are 0.72 (0.06) for the left LGN and 0.77 (0.07) for the right LGN. LGN-based tractography shows the subcortical pathway seeding from LGN passes the optic tract and also reaches V1 through the optic radiation, which is consistent with the LGN location in the visual system. In addition, LGN asymmetry as well as LGN atrophy along with age is observed in normal controls. The investigation of glaucoma effects on LGN volumes demonstrates that the bilateral LGN volumes shrink in patients. COMPARISON WITH EXISTING METHODS: The automatic LGN segmentation is objective, efficient, valid and applicable. CONCLUSIONS: Experiment results proved the validity and applicability of the algorithm. Our method will speed up the research on visual system and greatly enhance studies of different vision-related diseases. PMID- 26279342 TI - A novel approach for monitoring writing interferences during navigated transcranial magnetic stimulation mappings of writing related cortical areas. AB - BACKGROUND: It has recently been shown that navigated repetitive transcranial magnetic stimulation (nTMS) is useful in preoperative neurosurgical mapping of motor and language brain areas. In TMS mapping of motor cortices the evoked responses can be quantitatively monitored by electromyographic (EMG) recordings. No such setup exists for monitoring of writing during nTMS mappings of writing related cortical areas. NEW METHOD: We present a novel approach for monitoring writing during nTMS mappings of motor writing related cortical areas. COMPARISON WITH EXISTING METHOD(S): To our best knowledge, this is the first demonstration of quantitative monitoring of motor evoked responses from hand by EMG, and of pen related activity during writing with our custom made pen, together with the application of chronometric TMS design and patterned protocol of rTMS. RESULTS: The method was applied in four healthy subjects participating in writing during nTMS mapping of the premotor cortical area corresponding to BA 6 and close to the superior frontal sulcus. The results showed that stimulation impaired writing in all subjects. The corresponding spectra of measured signal related to writing movements was observed in the frequency band 0-20 Hz. Magnetic stimulation affected writing by suppressing normal writing frequency band. CONCLUSION: The proposed setup for monitoring of writing provides additional quantitative data for monitoring and the analysis of rTMS induced writing response modifications. The setup can be useful for investigation of neurophysiologic mechanisms of writing, for therapeutic effects of nTMS, and in preoperative mapping of language cortical areas in patients undergoing brain surgery. PMID- 26279343 TI - What's wrong with my mouse cage? Methodological considerations for modeling lifestyle factors and gene-environment interactions in mice. AB - The mechanistic understanding of lifestyle contributions to disease has been largely driven by work in laboratory rodent models using environmental interventions. These interventions show an array of methodologies and sometimes unclear collective conclusions, hampering clinical interpretations. Here we discuss environmental enrichment, exercise and stress interventions to illustrate how different protocols can affect the interpretations of environmental factors in disease. We use Huntington's disease (HD) as an example because its mouse models exhibit excellent validity and HD was the first genetic animal model in which environmental stimulation was found to be beneficial. We make a number of observations and recommendations. Firstly, environmental enrichment and voluntary exercise generally show benefits across laboratories and mouse models. However, the extent to which these environmental interventions have beneficial effects depends on parameters such as the structural complexity of the cage in the case of enrichment, the timing of the intervention and the nature of the control conditions. In particular, clinical interpretations should consider deprived control living conditions and the ethological relevance of the enrichment. Secondly, stress can have negative effects on the phenotype in mouse models of HD and other brain disorders. When modeling stress, the effects of more than one type of experimental stressor should be investigated due to the heterogeneity and complexity of stress responses. With stress in particular, but ideally in all studies, both sexes should be used and the randomized group sizes need to be sufficiently powered to detect any sex effects. Opportunities for clinical translation will be guided by the 'environmental construct validity' of the preclinical data, including the culmination of complementary protocols across multiple animal models. Environmental interventions in mouse models of HD provide illustrative examples of how valid preclinical studies can lead to conclusions relevant to clinical populations. PMID- 26279344 TI - A system to measure the Optokinetic and Optomotor response in mice. AB - BACKGROUND: Visually evoked compensatory head movements (Optomotor responses) or eye movements (Optokinetic responses) are extensively used in experimental mouse models for developmental defects, pathological conditions, and testing the efficacy of therapeutic manipulations. NEW METHOD: We present an automated system to measure Optomotor and Optokinetic responses under identical stimulation conditions, enabling a direct comparison of the two reflexes. A semi-automated calibration procedure and a commercial eye tracker are used to record angular eye velocity in the restrained animal. Novel video tracking algorithms determine the location of the mouse head in real time and allow repositioning of the stimulus relative to the mouse head. RESULTS: Optomotor and Optokinetic responses yield comparable results with respect to determining visual acuity in mice. Our new head tracking algorithms enable a far more accurate analysis of head angle determination, and reveal individual head retractions, analogous to saccadic eye movements observed during Optokinetic Nystagmus. COMPARISON WITH EXISTING METHODS: To our knowledge this is the first apparatus allowing the direct comparison of Optomotor and Optokinetic responses in mice. Our tracking algorithms, which allow an objective determination of head movements are a significant increment over existing systems which rely on subjective human observation. The increased accuracy of the novel algorithms increases the robustness of automated Optomotor response determinations and reveals novel aspects of this reflex. CONCLUSIONS: We provide the blueprints for inexpensive hardware, and release open source software for our system, and describe an accurate and accessible method for Optomotor and Optokinetic response determination in mice. PMID- 26279345 TI - ddRAD-seq phylogenetics based on nucleotide, indel, and presence-absence polymorphisms: Analyses of two avian genera with contrasting histories. AB - Genotype-by-sequencing (GBS) methods have revolutionized the field of molecular ecology, but their application in molecular phylogenetics remains somewhat limited. In addition, most phylogenetic studies based on large GBS data sets have relied on analyses of concatenated data rather than species tree methods that explicitly account for genealogical stochasticity among loci. We explored the utility of "double-digest" restriction site-associated DNA sequencing (ddRAD-seq) for phylogenetic analyses of the Lagonosticta firefinches (family Estrildidae) and the Vidua brood parasitic finches (family Viduidae). As expected, the number of homologous loci shared among samples was negatively correlated with genetic distance due to the accumulation of restriction site polymorphisms. Nonetheless, for each genus, we obtained data sets of ~3000 loci shared in common among all samples, including a more distantly related outgroup taxon. For all samples combined, we obtained >1000 homologous loci despite ~20my divergence between estrildid and parasitic finches. In addition to nucleotide polymorphisms, the ddRAD-seq data yielded large sets of indel and locus presence-absence polymorphisms, all of which had higher consistency indices than mtDNA sequence data in the context of concatenated parsimony analyses. Species tree methods, using individual gene trees or single nucleotide polymorphisms as input, generated results broadly consistent with analyses of concatenated data, particularly for Lagonosticta, which appears to have a well resolved, bifurcating history. Results for Vidua were also generally consistent across methods and data sets, although nodal support and results from different species tree methods were more variable. Lower gene tree congruence in Vidua is likely the result of its unique evolutionary history, which includes rapid speciation by host shift and occasional hybridization and introgression due to incomplete reproductive isolation. We conclude that ddRAD-seq is a cost-effective method for generating robust phylogenetic data sets, particularly for analyses of closely related species and genera. PMID- 26279346 TI - Molecular systematics and biogeography of the circumglobally distributed genus Seriola (Pisces: Carangidae). AB - The genus Seriola includes several important commercially exploited species and has a disjunct distribution globally; yet phylogenetic relationships within this genus have not been thoroughly investigated. This study reports the first comprehensive molecular phylogeny for this genus based on mitochondrial (Cytb) and nuclear gene (RAG1 and Rhod) DNA sequence data for all extant Seriola species (nine species, n=27). All species were found to be monophyletic based on Maximum parsimony, Maximum likelihood and Bayesian inference. The closure of the Tethys Sea (12-20 MYA) coincides with the divergence of a clade containing ((S. fasciata and S. peruana), S. carpenteri) from the rest of the Seriola species, while the formation of the Isthmus of Panama (+/-3 MYA) played an important role in the divergence of S. fasciata and S. peruana. Furthermore, factors such as climate and water temperature fluctuations during the Pliocene played important roles during the divergence of the remaining Seriola species. PMID- 26279347 TI - Oxygen saturation, red blood cell tissue fraction and speed resolved perfusion - A new optical method for microcirculatory assessment. AB - We have developed a new fiber-optic system that combines diffuse reflectance spectroscopy (DRS) and laser Doppler Flowmetry (LDF) for a multi-modal assessment of the microcirculation. Quantitative data is achieved with an inverse Monte Carlo algorithm based on an individually adaptive skin model. The output parameters are calculated from the model and given in absolute units: hemoglobin oxygen saturation (%), red blood cell (RBC) tissue fraction (%), and the speed resolved RBC perfusion separated into three speed regions; 0-1mm/s, 1-10mm/s and above 10mm/s (% mm/s). The aim was to explore microcirculatory parameters using the new optical method, integrating DRS and LDF in a joint skin model, during local heating of the dorsal foot and venous and arterial occlusion of the forearm in 23 healthy subjects (age 20-28years). There were differences in the three speed regions in regard to blood flow changes due to local heating, where perfusion for high speeds increased the most. There was also a high correlation between changes in oxygenation and changes in perfusion for higher speeds. Oxygen saturation at baseline was 44% on foot, increasing to 83% at plateau after heating. The larger increase in perfusion for higher speeds than for lower speeds together with the oxygenation increase during thermal provocation, shows a local thermoregulatory blood flow in presumably arteriolar dermal vessels. In conclusion, there are improved possibilities to assess microcirculation using integrated DRS and LDF in a joint skin model by enabling both oxygenation and speed resolved blood flow assessment simultaneously and in the same skin site. Output parameters in absolute units may also yield new insights about the microcirculatory system. PMID- 26279348 TI - Cryoablation for managing Barrett's esophagus refractory to radiofrequency ablation? Don't embrace the cold too soon! PMID- 26279349 TI - Duodenoscope reprocessing: risk and options coming into view. PMID- 26279350 TI - Position change during colonoscopy: the oldest and best trick in the book. PMID- 26279351 TI - Measuring the quality of colonoscopy: Where are we now and where are we going? PMID- 26279352 TI - Method for assessing the microbial contamination of GI endoscopes. PMID- 26279353 TI - Response. PMID- 26279354 TI - Response. PMID- 26279355 TI - Factors affecting bowel preparation and adenoma detection: patient or the doctor. PMID- 26279356 TI - Diagnosing adult celiac disease: A case for being less random with duodenal biopsies? PMID- 26279357 TI - A rare adverse event resulting from the use of a lumen-apposing metal stent for drainage of a pancreatic fluid collection: "the buried stent". PMID- 26279358 TI - EUS-guided transesophageal drainage of peripancreatic fluid collections in children. PMID- 26279359 TI - The investigation of EEG specificity in epileptic children during Depakine therapy. AB - BACKGROUND: Antiepileptic drug (AED) therapy in epileptic children can be optimized via an anticipation of AED efficacy during early stages of therapy. We hypothesize that the comprehensive EEG evaluation can determine AED efficacy in epileptic children. Thus, this study aimed to investigate the alteration of characteristics of interictal EEG during AED therapy. METHODS: Forty-three children aged 3-9 were investigated. EEGs were recorded three times: prior to Valproic Acid-Depakin (Dep) monotherapy and twice under Dep therapy (at three and six/eight months). Baseline EEG was analyzed for quantitative characteristics of interictal EEG such as absolute values of the power (AVP) spectra and EEG topography/Brain Mapping. The study involved epileptiform EEG and clinical condition assessments. RESULTS: Dep decreased AVP spectra in a low-frequency range, suppressed spontaneous epileptic discharge, and spike-wave complex 3/s. Dep partially decreased spikes-polyspikes, sharp waves, and generalized paroxysmal bursts during functional trials. Dep did not diminish rhythmic monomorphic theta-waves (RMT) of tempo-parietal localization observed by Brain Mapping. The presence of RMT correlated with the reocurrence of seizures if Dep was withdrawn. CONCLUSIONS: The findings of this study suggest that the presence of RMT with tempo-parietal localization on the interictal EEG can anticipate reocurrence of seizures if Dep dose will be reduced or withdrawn. The efficacy of AED-therapy can be revealed via reduction of low-frequency waves and suppression of epileptiform EEG elements parallel to clinical improvement. Thus, optimal treatment strategies can be tailored based on the evaluation of background EEG characteristics using spectral analysis, EEG mapping and the quantitative EEG approach. PMID- 26279360 TI - Interleukin 35: Critical regulator of immunity and lymphocyte-mediated diseases. AB - Cytokines coordinate the activities of innate and adaptive immune systems and the Interleukin 12 (IL-12) family of cytokines has emerged as critical regulators of immunity in infectious and autoimmune diseases. While some members (IL-12 and IL 23) are associated with the pathogenesis of chronic inflammatory diseases, others (IL-27 and IL-35) mitigate autoimmune diseases. Unlike IL-12, IL-23 and IL-27 that are produced mainly by antigen presenting cells, IL-35 is predominantly secreted by regulatory B (i35-Bregs) and T (iTR35) cells. The discovery that IL 35 can induce the conversion or expansion of lymphocytes to regulatory B and T cells has considerable implications for therapeutic use of autologous regulatory B and T cells in human diseases. Although our current understanding of the immunobiology of IL-35 or its subunits (p35 and Ebi3) is still rudimentary, our goal in this review is to summarize what we know about this enigmatic cytokine and its potential clinical use, particularly in the treatment of CNS autoimmune diseases. PMID- 26279361 TI - (1)H NMR-based urine metabolic profile of IUGR, LGA, and AGA newborns in the first week of life. AB - Under conditions of non-optimal supply of nutrients, maternal diet during gestation can alter the balance between anabolic and catabolic pathways of fetus and triggers an effect of programming to the metabolic syndrome. Metabolomics is an analytical technique that has been recently attracting increasing interest for the identification of biomarkers of dietary exposure. In this study, a NMR-based metabolomic approach was employed for an explorative analysis of the time-related urinary metabolic profiles of three groups of newborns receiving a different fetal nutrition: adequate for gestational age (AGA), with intrauterine growth retardation (IUGR), and large for gestational age (LGA). Urine samples were collected over the first week of life. Application of Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) evidenced similar time-related modifications in the metabolic profiles of the three classes of infants, consisting mainly of changes in levels of taurine, creatinine, betaine, and glycine. Furthermore, alterations in the content of citrate and myo-inositol were found to be characteristic of IUGR and LGA, whole levels were higher with respect to controls, while higher contents of betaine and succinate were noted in AGA. Our results positively support the application of the metabolomic approach in the study of the metabolic pathways associated to fetal malnutrition. PMID- 26279362 TI - Leptin in Alzheimer's disease. AB - Alzheimer's disease (AD) is the most common cause of progressive dementia in the elderly population. AD is histologically characterized by accumulation of amyloid beta protein (Abeta) on extracellular plaques and deposition of hyperphosphorylated tau protein in intracellular neurofibrillary tangles. Several studies have shown that obesity may precede dementia and that lifestyle factors play a critical role in the onset of AD. Furthermore, accumulating evidence indicates that obesity is an independent risk factor for developing AD. In this scenario, the understanding of the role of adipose tissue in brain health is essential to clarify the establishment of demential processes. The objective of this work was to review studies regarding leptin, an anorexigenic peptide hormone synthesized in adipocytes, in the context of dementia. Some authors proposed that leptin evaluation might be a better predictor of dementia than traditional anthropometric measures. Leptin, once established as a biomarker, could enhance the understanding of late-onset AD risk over the life course, as well as the clinical progression of prodromal state to manifested AD. Other studies have proposed that leptin presents neuroprotective activities, which could be explained by inhibiting the amyloidogenic process, reducing the levels of tau protein phosphorylation and improving the cognitive function. PMID- 26279363 TI - Evaluation of the Caprini Model for Venothromboembolism in Esophagectomy Patients. AB - BACKGROUND: Patients undergoing esophagectomy for cancer are in the highest-risk group for venous thromboembolism, with a 7.3% incidence reported by the National Surgical Quality Improvement Program. Venothromboembolism (VTE) doubles esophagectomy mortality. The Caprini risk assessment model (RAM) is a method to stratify postoperative thromboembolism risk for consideration of prolonged preventive anticoagulation in higher-risk patients. Our aim was to examine the potential use of this model for reducing the VTE incidence in esophagectomy patients. METHODS: The records of patients who underwent an esophagectomy by the thoracic surgery service at our institution between June 2005 and June 2013 were reviewed. The inclusion criteria were a diagnosis of esophageal cancer treated with esophagectomy (any approach) and with available 60-day postoperative follow up. Exclusion criteria were the presence of an inferior vena cava filter or chronic anticoagulation therapy. The Caprini risk score and the number of VTE events were recorded retrospectively for each patient. RESULTS: Seventy patients satisfied eligibility criteria. The VTE incidence was 14.3%. Patients with esophageal thromboembolism had a higher Caprini score distribution than patients without thromboembolism (p < 0.001). Adjusted logistic regression analysis demonstrated increased odds of VTE with increasing score (p < 0.05), with good discrimination. CONCLUSIONS: In this first report examining the Caprini model categories in an esophagectomy population, the VTE incidence in true high-risk patients was high. From this retrospective calculation of risk and events, patients in the highest-risk Caprini group may benefit from an enhanced course of postoperative anticoagulation. PMID- 26279364 TI - Impact of Intrauterine Growth Restriction on Cardiac Surgical Outcomes and Resource Use. AB - BACKGROUND: We sought to evaluate outcomes of congenital heart operations and resource use in patients with intrauterine growth restriction (IUGR). METHODS: This was a retrospective matched case-control study of 41 consecutive patients with IUGR matched 1:2 with a comparison cohort of 82 contemporaneous patients without IUGR who underwent congenital heart operations during the interval from January 1, 2000 to January 1, 2012. Matching was based on the Risk Adjustment for Congenital Heart Surgery (RACHS)-1 risk category, diagnostic category, age at operation, and gestational age. RESULTS: Operative mortality (6 of 41 cases [14.6%] for the study group versus 5 of 82 cases [6.1%] for controls) and any major adverse event (14 of 41 cases [34.2%] for the study group versus 23 of 82 cases [28%] for controls) occurred in a higher percentage of study patients, with insignificant p values. Important differences in secondary outcomes included the following: mean total length of stay (56.3 days versus 28.0 days for controls; p < 0.0001), postoperative days of mechanical ventilation (25.8 days versus 5.4 days for controls; p = 0.002), postoperative cardiopulmonary arrest (7 of 41 cases [17.1%] versus 4 of 82 cases [4.9%] for controls; p = 0.03), and postoperative infection (13 of 41 cases [31.7%] versus 13 of 81 cases [16.1%] for controls; p = 0.04). The mean charge for the study group was considerably higher than that for the control group: $493,915 versus $175,144; p < 0.0001. CONCLUSIONS: IUGR is associated with a substantially increased length of hospital stay, postoperative morbidity, and resource use. These findings are relevant to risk stratification, prognosis, and potentially to contracting and reimbursement. IUGR merits further attention as an important risk factor in congenital heart operations. PMID- 26279365 TI - Pure Bilateral Internal Thoracic Artery Grafting in Diabetic Patients With Triple Vessel Disease. AB - BACKGROUND: Despite the documented superior long-term patency of bilateral internal thoracic artery (BITA) grafting, use of BITAs remains low, especially in diabetic patients. We analyzed the results of pure BITA grafting to determine whether the potential survival advantage outweighs the risk of wound infection in diabetic patients. METHODS: We performed a retrospective analysis of 791 consecutive patients (389 diabetic, 402 nondiabetic) with triple-vessel disease who underwent off-pump coronary artery bypass using only skeletonized BITAs from 2001 to 2010. We used propensity score matching to match 315 nondiabetic patients with diabetic patients. RESULTS: The groups did not differ significantly regarding 10-year survival (diabetic, 84.2% +/- 4.5%; nondiabetic, 80.8% +/- 4.7%; p = 0.828) or freedom from major adverse cardiovascular events (diabetic, 73.5% +/- 5.2%; nondiabetic, 71.8% +/- 5.3%; p = 0.431). Diabetes was not predictive of deep sternal infection (odds ratio, 1.11; 95% confidence interval, 0.23 to 5.31; p = 0.895). Results of stratified competing risks regression analysis showed that the risk of target vessel revascularization in diabetic patients was similar to that of nondiabetic patients (subdistribution hazard ratio, 0.67; 95% confidence interval, 0.16 to 2.80; p = 0.585). CONCLUSIONS: Off pump coronary artery bypass grafting using pure BITAs produced excellent clinical outcomes in both diabetic and nondiabetic patients. This strategy did not increase the incidence of deep sternal infection in diabetic patients. We recommend BITA grafting, which has proven long-term patency, as a strategy of choice in diabetic patients. PMID- 26279366 TI - Ventricular Function Before and After Surgery for Isolated and Combined Regurgitation in the Young. AB - BACKGROUND: Chronic mitral and aortic regurgitation (MR and AR) are associated with progressive contractile dysfunction. In the young, the risk of left ventricle (LV) dysfunction after operation for isolated and combined AR and MR is poorly defined. We aimed to compare LV mechanics in children and young adults with isolated and combined AR and MR, and identify risk factors for LV dysfunction after valve surgery. METHODS: Echocardiograms from children and young adults undergoing surgery for isolated severe AR (group I, n = 14), MR (group II, n = 21), or combined AR and MR (group III, n = 13), before and up to 18 months after surgery were compared with a normal population (n = 89). Normalized measures of LV geometry and mechanics were expressed as z scores. RESULTS: Before surgery all groups had LV dilatation, while groups I and III had afterload elevation and LV dysfunction. After operation LV dysfunction was more common in group III than in groups I and II (11 [84.5%] vs 5 [35.7%] vs 12 [57.1%], p = 0.04). The preoperative end-systolic volume z score predicted LV dysfunction after surgery in group I and II patients (p = 0.047, area under the curve = 0.75) but not in group III, where moderate LV dysfunction was related to the preoperative stress velocity index (-2.6 with vs -1.1 without, p = 0.04). CONCLUSIONS: Left ventricular mechanics in combined AR and MR closely resemble those of AR. End-systolic volume predicts postoperative LV dysfunction in patients with isolated valve regurgitation, while those with combined disease were at high risk of postoperative LV dysfunction. PMID- 26279367 TI - Clinical Prediction of Pathologic Complete Response in Superior Sulcus Non-Small Cell Lung Cancer. AB - BACKGROUND: Management of superior sulcus non-small cell lung cancer (NSCLC) continues to evolve, with preoperative chemoradiotherapy (CXRT) followed by surgical intervention supported by several studies. Rates of pathologic complete response (pCR) have varied, and previous attempts to identify clinical predictors of pCR have been unsuccessful. We analyzed our experience with resected superior sulcus NSCLC to elucidate clinical features suggestive of pCR among patients after preoperative treatment. METHODS: A multiinstitutional retrospective review was performed in patients who underwent resection for superior sulcus NSCLC between January 1988 and July 2013. Data pertaining to comorbidities, staging, therapy, imaging, and outcomes were collected. Logistic regression was performed to identify predictors of survival and pCR. RESULTS: During the study, 102 patients underwent preoperative therapy, consisting of CXRT in 75 (73.5%), chemotherapy in 15 (14.7%), and radiotherapy in 12 (11.8%). After median follow up of 18.0 months, overall and disease-free survivals were 51.0% and 45.1%, respectively. On multivariate regression, independent predictors of survival included pCR (p = 0.001; hazard ratio [HR], 0.243; 95% confidence interval [CI], 0.106-0.555) and age (p = 0.007; HR, 1.049; CI, 1.013-1.085). Among those who received CXRT, 24 of 75 (32%) achieved pCR. Multivariate regression analysis of the CXRT group revealed that pCR was independently predicted by extent of size reduction on imaging (p = 0.015; HR, 1.042; CI, 1.008-1.078), with histologic examination showing a trend toward significance (p = 0.073). CONCLUSIONS: Preoperative chemoradiation frequently resulted in pCR, and treatment response on imaging was associated with the likelihood of achieving pCR. Future investigations are warranted to further predict pCR from preoperative clinical variables such as symptom resolution, as identification of accurate predictors may ultimately permit the application of selective surgical intervention in superior sulcus NSCLC. PMID- 26279368 TI - Pharmacokinetics in rats and tissue distribution in mouse of berberrubine by UPLC MS/MS. AB - Berberrubine is an isoquinoline alkaloid isolated from Berberis vulgaris L, and it is readily derived from berberine. In this study, a sensitive and selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of berberrubine in rat plasma and mouse tissue has been developed. Magnoflorine was employed as an internal standard (IS), and liquid-liquid extraction by ethyl acetate was used for sample preparation. Chromatographic separation was achieved on a UPLC BEH C18 column (2.1mm*100mm, 1.7MUm) with 0.1% formic acid and acetonitrile as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; multiple reactions monitoring (MRM) mode was used for quantification using target fragment ions m/z 322.0->307.0 for berberrubine and m/z 342.8->298.2 for IS. Calibration plots were linear in the range of 2-2000ng/mL for berberrubine in rat plasma and mouse tissue. Mean recoveries of berberrubine in rat plasma ranged from 79.6% to 84.8%. Intra-day and inter-day precision were less than 11%. The accuracy ranged from 93.6% to 106.8%. The method has also been successfully applied in pharmacokinetics and tissue distribution study of berberrubine. The absolute bioavailability of berberrubine was determined to be 31.6%. The results also show that berberrubine is rapidly absorbed and widely distributed in various tissues. The level of berberrubine in liver is highest, and followed by kidney, spleen and heart. Furthermore, the concentration of berberrubine in various tissues could also be predicted by a BP-ANN model. PMID- 26279369 TI - Forced degradation of fingolimod: effect of co-solvent and characterization of degradation products by UHPLC-Q-TOF-MS/MS and 1H NMR. AB - Fingolimod (FGL), an immunomodulator drug for treating multiple sclerosis, was subjected to hydrolysis (acidic, alkaline and neutral), oxidation, photolysis and thermal stress, as per International Conference on Harmonization specified conditions. The drug showed extensive degradation under base hydrolysis, however, it was stable under all other conditions. A total of three degradation products (DPs) were observed. The chromatographic separation of the drug and its degradation products was achieved on a Fortis C18 (100*2.1mm, 1.7MUm) column with a mobile phase composed of 0.1% formic acid (Solvent A) and acetonitrile (Solvent B) in gradient mode. All the DPs were identified and characterized by liquid chromatography-quadrupole time of flight-mass spectrometry (LC-Q-TOF-MS) in combination with accurate mass measurements. The major DP was isolated and characterized by Nuclear Magnetic resonance spectroscopy. This is a typical case of degradation where acetonitrile used as co-solvent in stress studies, reacts with FGL in base hydrolytic conditions to produce acetylated DPs. Hence, it can be suggested that acetonitrile is not preferable as a co-solvent for stress degradation of FGL. The developed UHPLC method was validated as per ICH guidelines. PMID- 26279370 TI - Metabolic characterization of natural and cultured Ophicordyceps sinensis from different origins by 1H NMR spectroscopy. AB - Ophicordyceps sinensis is a well-known traditional Chinese medicine and cultured mycelium is a substitute for wild O. sinensis. Metabolic profiles of wild O. sinensis from three geographical locations and cultivated mycelia derived from three origins were investigated using (1)H nuclear magnetic resonance (NMR) analysis combined with multivariate statistical analysis. A total of 56 primary metabolites were identified and quantified from O. sinensis samples. The principle component analysis (PCA) showed significant differences between natural O. sinensis and fermentation mycelia. Seven metabolites responsible for differentiation were screened out by orthogonal partial least squares discriminant analysis (OPLS-DA). The concentrations of mannitol, trehalose, arginine, trans-4-hydroxyproline, alanine and glucitol were significantly different between wild and cultured groups. The variation in metabolic profiling among artificial mycelia was greater than that among wild O. sinensis. Furthermore, wild samples from different origins were clearly distinguished by the levels of mannitol, trehalose and some amino acids. This study indicates that (1)H NMR-based metabolomics is useful for fingerprinting and discriminating O. sinensis of different geographical regions and cultivated mycelia of different strains. The present study provided an efficient approach for investigating chemical compositions and evaluating the quality of medicine and health food derived from O. sinensis. PMID- 26279371 TI - Development of a nucleotide sugar purification method using a mixed mode column & mass spectrometry detection. AB - Analysis of nucleotide sugars, nucleoside di- and triphosphates and sugar phosphates is an essential step in the process of understanding enzymatic pathways. A facile and rapid separation method was developed to analyze these compounds present in an enzymatic reaction mixture utilized to produce nucleotide sugars. The Primesep SB column explored in this study utilizes hydrophobic interactions as well as electrostatic interactions with the phosphoric portion of the nucleotide sugars. Ammonium formate buffer was selected due to its compatibility with mass spectrometry. Negative ion mode mass spectrometry was adopted for detection of the sugar phosphate (fucose-1-phophate), as the compound is not amenable to UV detection. Various mobile phase conditions such as pH, buffer concentration and organic modifier were explored. The semi-preparative separation method was developed to prepare 30mg of the nucleotide sugar. (19)F NMR was utilized to determine purity of the purified fluorinated nucleotide sugar. The collected nucleotide sugar was found to be 99% pure. PMID- 26279372 TI - Mechanisms of BMP-Receptor Interaction and Activation. AB - Bone morphogenetic proteins (BMPs), together with the eponymous transforming growth factor (TGF) beta and the Activins form the TGFbeta superfamily of ligands. This protein family comprises more than 30 structurally highly related proteins, which determine formation, maintenance, and regeneration of tissues and organs. Their importance for the development of multicellular organisms is evident from their existence in all vertebrates as well as nonvertebrate animals. From their highly specific functions in vivo either a strict relation between a particular ligand and its cognate cellular receptor and/or a stringent regulation to define a distinct temperospatial expression pattern for the various ligands and receptor is expected. However, only a limited number of receptors are found to serve a large number of ligands thus implicating highly promiscuous ligand receptor interactions instead. Since in tissues a multitude of ligands are often found, which signal via a highly overlapping set of receptors, this raises the question how such promiscuous interactions between different ligands and their receptors can generate concerted and highly specific cellular signals required during embryonic development and tissue homeostasis. PMID- 26279373 TI - The Bone Morphogenetic Proteins and Their Antagonists. AB - The bone morphogenetic proteins (BMPs) and the growth and differentiation factors comprise a single family of some 20 homologous, dimeric cytokines which share the cystine-knot domain typical of the TGF-beta superfamily. They control the differentiation and activity of a range of cell types, including many outside bone and cartilage. They serve as developmental morphogens, but are also important in chronic pathologies, including tissue fibrosis and cancer. One mechanism for enabling tight spatiotemporal control of their activities is through a number of antagonist proteins, including Noggin, Follistatin, Chordin, Twisted gastrulation (TSG), and the seven members of the Cerberus and Dan family. These antagonists are secreted proteins that bind selectively to particular BMPs with high affinity, thereby blocking receptor engagement and signaling. Most of these antagonists also possess a TGF-beta cystine-knot domain. Here, we discuss current knowledge and understanding of the structures and activities of the BMPs and their antagonists, with a particular focus on the latter proteins. Recent advances in structural biology of BMP antagonists have begun the process of elucidating the molecular basis of their activity, displaying a surprising variety between the modes of action of these closely related proteins. We also discuss the interactions of the antagonists with the glycosaminoglycan heparan sulfate, which is found ubiquitously on cell surfaces and in the extracellular matrix. PMID- 26279374 TI - BMP-7 Signaling and its Critical Roles in Kidney Development, the Responses to Renal Injury, and Chronic Kidney Disease. AB - Chronic kidney disease (CKD) is a significant health problem that most commonly results from congenital abnormalities in children and chronic renal injury in adults. The therapeutic potential of BMP-7 was first recognized nearly two decades ago with studies demonstrating its requirement for kidney development and ability to inhibit the pathogenesis of renal injury in models of CKD. Since this time, our understanding of CKD has advanced considerably and treatment strategies have evolved with the identification of many additional signaling pathways, cell types, and pathologic processes that contribute to disease progression. The purpose of this review is to revisit the seminal studies that initially established the importance of BMP-7, highlight recent advances in BMP-7 research, and then integrate this knowledge with current research paradigms. We will provide an overview of the evolutionarily conserved roles of BMP proteins and the features that allow BMP signaling pathways to function as critical signaling nodes for controlling biological processes, including those related to CKD. We will discuss the multifaceted functions of BMP-7 during kidney development and the potential for alterations in BMP-7 signaling to result in congenital abnormalities and pediatric kidney disease. We will summarize the renal protective effects of recombinant BMP-7 in experimental models of CKD and then propose a model to describe the potential physiological role of endogenous BMP-7 in the innate repair mechanisms of the kidneys that respond to renal injury. Finally, we will highlight emerging clinical approaches for applying our knowledge of BMP-7 toward improving the treatment of patients with CKD. PMID- 26279375 TI - The Role of BMP Signaling and NF-kappaB Signaling on Osteoblastic Differentiation, Cancer Development, and Vascular Diseases--Is the Activation of NF-kappaB a Friend or Foe of BMP Function? AB - Bone morphogenetic proteins (BMPs), members of the transforming growth factor beta family, were first identified as potent inducers of ectopic bone formation when implanted into muscle tissue. Subsequent studies have demonstrated that BMPs play important roles during developmental processes, including cell proliferation, differentiation, and apoptosis. Furthermore, recent studies have shown that BMPs are also involved in the initiation and/or progression of various diseases, such as skeletal diseases, cancer, and vascular diseases. Nuclear factor kappa light-chain enhancer of activated B cells (NF-kappaB) was originally identified as a transcription factor that bound to the enhancer region of the immunoglobulin kappa light-chain promoter in B cells. A wide range of stimuli, including inflammatory cytokines and bacterial and viral products, activate the NF-kappaB pathway, leading to the expression of NF-kappaB target genes. NF-kappaB also has functions in multiple biological processes, such as immune and inflammatory responses, cell differentiation, cellular stress responses, and cancer development. Recent findings have demonstrated that BMP and NF-kappaB signaling agonistically or antagonistically regulate bone development, cancer development, and vascular diseases. This review describes the role of BMPs and NF kappaB in bone development, cancer development, and vascular diseases with special attention given to concepts that have emerged in recent years. PMID- 26279376 TI - Bone Morphogenetic Protein Signaling Regulates Development and Activation of CD4(+) T Cells. AB - Bone morphogenetic proteins (BMPs) are growth factors belonging to the TGF-beta (transforming growth factor beta) superfamily. BMPs were found to regulate multiple cell processes such as proliferation, survival, differentiation, and apoptosis. They were originally described to play a pivotal role in inducing bone, cartilage, ligament, and tendon formation at both heterotopic and orthotopic sites but were found to play a significant role in embryogenesis and development of multiple tissues and organs. Activities of BMPs are regulated by a number of secreted proteins, which modulate their availability to bind cellular receptors. The functions of individual BMPs are highly redundant due to binding the same receptors and inducing overlapping signal transduction pathways. Recently, BMPs were found to regulate cells of the innate and adaptive immune system. BMPs are involved in thymic development of T cells at the early, double negative, as well as later, double positive, stages of thymopoesis. They specifically modulate thymic development of regulatory T cells (T(reg)). In the periphery, BMPs affect T cell activation, promoting generation of T(reg) cells. We found that mice deficient for one of the receptors activated by BMPs demonstrated slower growth of transplantable melanoma tumors. PMID- 26279378 TI - Bone Morphogenetic Proteins in Preimplantation Embryos. AB - The bone morphogenetic proteins' (BMPs) pathway is one of the evolutionarily oldest used by animal embryos and is required for dorsal-ventral patterning of the early embryo of both vertebrates and invertebrates. Nevertheless, the role of this system in preimplantation embryo development has not been extensively studied yet. Taking into account that the preimplantation period is different among species though the BMP system is conserved, information regarding comparative embryo development and the role of BMPs in different mammalian models is revised and discussed in this chapter. BMP system is expressed by maternal tissues (the ovary, the oviduct, and the uterus) as well as by the embryo and extraembryonic tissues. The reviewed information demonstrates a very important role for BMP signaling system at different stages of embryo preimplantation development from acquisition of gamete competence to regulation of trophoblast development and differentiation in mice as well as in ungulates. PMID- 26279377 TI - Bone Morphogenetic Proteins: Inhibitors of Myelination in Development and Disease. AB - Myelin, the lipid membrane that surrounds axons, is critical for the propagation of nervous impulses and axonal maintenance. The destruction of myelin or lack of myelin formation due to disease or injury causes severe motor and cognitive disability. Regeneration of myelin is theoretically possible but rarely happens. Myelin is synthesized as the plasma membrane of the oligodendrocyte in the central nervous system. During development, myelin and oligodendrocytes are generated from oligodendrocyte progenitors through a process modulated by extrinsic growth factors signaling to cell-intrinsic proteins. Among the key extrinsic factors are the bone morphogenetic proteins (BMPs), potent inhibitors of oligodendrocyte differentiation and myelin protein expression, likely serving to regulate myelination temporally and spatially. BMPs also promote astrocyte generation. Given the inhibitory role of BMP in oligodendrogliogenesis during development, the expression of BMP during demyelinating disease or injury was investigated, as was whether BMP upregulation could serve to prevent regeneration by both direct inhibition of myelination and increases in astrogliosis. BMPs, predominantly BMP4, were increased in animal models of spinal cord injury, stroke, multiple sclerosis, and perinatal white matter injury. A number of studies inhibited BMP signaling by infusing the injury site with the BMP-specific inhibitor noggin or transplanting stem cells engineered to secrete noggin. In most cases, noggin increased the numbers of mature oligodendrocytes and decreased numbers of astrocytes. Some studies also showed functional improvement. BMP is one of several inhibitory growth factors that now appear to inhibit myelin regeneration. Common downstream mechanisms among these factors are likely to be identified. PMID- 26279379 TI - Strategies of Manipulating BMP Signaling in Microgravity to Prevent Bone Loss. AB - Bone structure and function is shaped by gravity. Prolonged exposure to microgravity leads to 1-2% bone loss per month in crew members compared to 1% bone loss per year in postmenopausal women. Exercise countermeasures developed to date are ineffective in combating bone loss in microgravity. The search is on for alternate therapies to prevent bone loss in space. Microgravity is an ideal stimulus to understand bone interactions at different levels of organizations. Spaceflight experiments are limited by high costs and lack of opportunity. Ground based microgravity analogs have proven to simulate biological responses in space. Mice experiments have given important signaling clues in microgravity-associated bone loss, but are restricted by numbers and human application. Cell-based systems provide initial clues to signaling changes; however, the information is simplistic and limited to the cell type. There is a need to integrate information at different levels and provide a complete picture which will help develop a unique strategy to prevent bone weakening. Limited exposure to simulated microgravity using random positioning machine induces proliferation and differentiation of bipotential murine oval liver stem cells. Bone morphogenetic proteins (BMPs) are the prototypal osteogenic signaling molecule with multitude of bone protective functions. In this chapter, we discuss the basic BMP structure, its significance in bone repair, and stem cell differentiation in microgravity. Based on the current information, we propose a model for BMP signaling in space. Development of new technologies may help osteoporosis patients, bedridden people, spinal injuries, or paralytic patients. PMID- 26279380 TI - Bmpr1a Signaling in Cartilage Development and Endochondral Bone Formation. AB - The type IA bone morphogenetic protein receptor (Bmpr1a), encoded by 11 exons and spanning about 40 kb on chromosome 14 in mice and chromosome 10 in human (Derynck & Feng, 1997; Mishina, Hanks, Miura, Tallquist, & Behringer, 2002), is an essential receptor for BMP signaling. This chapter focuses on the current understanding of the role of Bmpr1a in cartilage development and endochondral ossification, including formation of the mesenchymal condensation, chondrocyte differentiation and maturation, and endochondral bone development. PMID- 26279381 TI - Bone Morphogenetic Proteins: Promising Molecules for Bone Healing, Bioengineering, and Regenerative Medicine. AB - Bone morphogenetic proteins (BMPs), glycoproteins secreted by some cells, are members of the TGF-beta superfamily that have been implicated in a wide variety of roles. Currently, about 20 different BMPs have been identified and grouped into subfamilies, according to similarities with respect to their amino acid sequences. It has been shown that BMPs are secreted growth factors involved in mesenchymal stem cell differentiation, also being reported to control the differentiation of cancer stem cells. BMPs initiate signaling from the cell surface by binding to two different receptors (R: Type I and II). The heterodimeric formation of type I R and II R may occur before or after BMP binding, inducing signal transduction pathways through SMADs. BMPs may also signal through SMAD-independent pathways via mitogen-activated protein kinases (ERK, p38MAPKs, JNK). BMPs may act in an autocrine or paracrine manner, being regulated by specific antagonists, namely: noggin and chordin. Genetic engineering allows the production of large amounts of BMPs for clinical use, and clinical trials have shown the benefits of FDA-approved recombinant human BMPs 2 and 7. Several materials from synthetic to natural sources have been tested as BMP carriers, ranging from hydroxyapatite, and organic polymers to collagen. Bioactive membranes doped with BMPs are promising options, acting to accelerate and enhance osteointegration. The development of smart materials, mainly based on biopolymers and bone-like calcium phosphates, appears to provide an attractive alternative for delivering BMPs in an adequately controlled fashion. BMPs have revealed a promising future for the fields of Bioengineering and Regenerative Medicine. In this chapter, we review and discuss the data on BMP structure, mechanisms of action, and possible clinical applications. PMID- 26279382 TI - Bone Morphogenic Protein. Preface. PMID- 26279383 TI - Roaming as the dominant mechanism for molecular products in the photodissociation of large aliphatic aldehydes. AB - Photodissociation of isobutyraldehyde (C3H7CHO) at 248 nm is investigated using time-resolved Fourier-transform infrared emission spectroscopy to demonstrate the growing importance of the roaming pathway with increasing molecular size of aliphatic aldehydes. Each acquired CO rotational distribution from v = 1 to 4 is well characterized by a single Boltzmann rotational temperature from 637 to 750 K, corresponding to an average rotational energy of 5.9 +/- 0.6 kJ mol(-1). The roaming signature that shows a small fraction of CO rotational energy disposal accompanied by a vibrationally hot C3H8 co-fragment is supported by theoretical prediction. The energy difference between the tight transition state (TS) and the roaming saddle point (SP) is found to be -27, 4, 15, 22, and 30 kJ mol(-1) for formaldehyde, acetaldehyde, propionaldehyde, isobutyraldehyde, and 2,2-dimethyl propanal, respectively. The roaming SP is stabilized by a larger alkyl moiety. It is suggested that the roaming photodissociation rate of aldehydes increasingly exceeds those via the tight TS, resulting in the dominance of the CO + alkane products, as the size of aldehydes becomes larger. Along with formaldehyde, acetaldehyde, and propionaldehyde, in this work isobutyraldehyde is further demonstrated that this aldehyde family with special functional group is the first case in the organic compound to follow predominantly a roaming dissociation pathway, as the molecular size becomes larger. PMID- 26279384 TI - Reframing and understanding the HIV epidemic in MSM: masculinity, racism, and homophobia. PMID- 26279386 TI - Meaning of care for terminally Ill HIV-infected patients by HIV-infected peer caregivers in a simulation-based training program in South Korea. AB - The purpose of this study was to develop a simulation-based training program for people living with HIV (PLWH) as peer caregivers who would take care of terminally ill, HIV-infected patients. We used qualitative research methods and standardized patients to explore the meaning of caring for patients as peer caregivers. Study participants included 32 patients registered as PLWH at the South Korea Federation for HIV/AIDS. The meanings of peer caregiving were categorized into four dimensions: physical, psychological, relational, and economic. Our study had benefits in knowledge acquisition for caregivers as well as care recipients, empathy with HIV-infected care recipients, improvement in self-esteem and social participation, and financial self-sufficiency to enable independent living for caregivers. The simulation training program for PLWH peer caregivers for terminally ill HIV-infected patients demonstrated value, for both PLWH caregivers and terminally ill HIV-infected patients in South Korea, to improve the quality of care. PMID- 26279385 TI - Provider perspectives regarding the health care needs of a key population: HIV infected prisoners after incarceration. AB - During incarceration, many HIV-infected prisoners receive care and are adherent to medication. However, following release, many have difficulty engaging in HIV care and remaining on antiretroviral therapy. Community-based service providers for HIV-infected releasees have a deep understanding of the health needs and challenges these individuals face on community re-entry. We conducted in-depth qualitative interviews with 38 health care and service professionals in two southern U.S. states regarding the barriers releasees faced in meeting their health needs, including HIV care and treatment post release. Individual, community, and organization-level barriers to HIV care and treatment adherence post release were identified, and offered unique insight into the ways that these multilevel obstacles affect HIV-infected former prisoners' abilities to engage in care and access necessary social services. Provider perspectives should be considered when designing interventions to support HIV care after release. PMID- 26279387 TI - Applying qualitative data derived from a Rapid Assessment and Response (RAR) approach to develop a community-based HIV prevention program for adolescents in Thailand. AB - HIV education programs are needed to address risk-taking behavior for adolescents. The purpose of our study was to use the World Health Organization's Rapid Assessment and Response (RAR) method to design a community-based, cultural- and age-appropriate HIV prevention program for adolescents in Bangkok, Thailand. Adolescent single-gender-specific focus groups (n = 3; 28 participants) were used to gather reactions/ideas about program topics/approaches. An adult, mixed-gender group was held to review information identified by adolescents. Sessions were audiotaped and transcribed verbatim. Themes regarding HIV content and the process of implementation emerged from a qualitative content analysis of the data. Community representatives recommended incorporation of HIV information and risk prevention skills. Information delivery suggestions included small group discussions, interactive games/role-playing, program materials/terminology, and HIV-infected program facilitators. Community members provided critical input toward an HIV prevention program tailored to meet adolescents' unique needs/interests. The RAR model provides opportunities to engage communities in developing health-related interventions. PMID- 26279388 TI - Are psychological interventions effective for the management of neck pain and whiplash-associated disorders? A systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration. AB - BACKGROUND CONTEXT: In 2008, the lack of published evidence prevented the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders (Neck Pain Task Force [NPTF]) from commenting on the effectiveness of psychological interventions for the management of neck pain. PURPOSE: This study aimed to update findings of the NPTF and evaluate the effectiveness of psychological interventions for the management of neck pain and associated disorders (NAD) or whiplash-associated disorders (WAD). STUDY DESIGN/SETTING: This study used systematic review and best-evidence synthesis. SAMPLE: Randomized controlled trials, cohort studies, and case-control studies comparing psychological interventions to other non-invasive interventions or no intervention were the samples used in this study. OUTCOME MEASURES: The outcome measures are (1) self-rated recovery; (2) functional recovery; (3) clinical outcomes; (4) administrative outcomes; and (5) adverse effects. METHODS: We searched six databases from 1990 to 2015. Randomized controlled trials, cohort studies, and case-control studies meeting our selection criteria were eligible for critical appraisal. Random pairs of independent reviewers used the Scottish Intercollegiate Guidelines Network criteria to critically appraise eligible studies. Studies with a low risk of bias were synthesized following best evidence synthesis principles. This study was funded by the Ontario Ministry of Finance. RESULTS: We screened 1,919 articles, 19 were eligible for critical appraisal and 10 were judged to have low risk of bias. We found no clear evidence supporting relaxation training or cognitive behavioral therapy (CBT) for persistent grades I III NAD for reducing pain intensity or disability. Similarly, we did not find evidence to support the effectiveness of biofeedback or relaxation training for persistent grade II WAD, and there is conflicting evidence for the use of CBT in this population. However, adding a progressive goal attainment program to functional restoration physiotherapy may benefit patients with persistent grades I-III WAD. Furthermore, Jyoti meditation may help reduce neck pain intensity and bothersomeness in patients with persistent NAD. CONCLUSIONS: We did not find evidence for or against the use of psychological interventions in patients with recent onset NAD or WAD. We found evidence that a progressive goal attainment program may be helpful for the management of persistent WAD and that Jyoti meditation may benefit patients with persistent NAD. The limited evidence of effectiveness for psychological interventions may be due to several factors, such as interventions that are ineffective, poorly conceptualized, or poorly implemented. Further methodologically rigorous research is needed. PMID- 26279390 TI - A trajectory towards partnership in care--Patient experiences of autonomy in intensive care: A qualitative study. AB - OBJECTIVE: The aim of this study was to describe and elucidate patient experiences of autonomy in an intensive care context from a caring perspective. BACKGROUND: Patients in intensive care units (ICUs) are critically ill and in a dependent and vulnerable position. There is thus a risk of staff taking command not only of the patients' vital functions but also of their decision-making. METHODS: A qualitative design was selected. Individual interviews were conducted with 11 adult patients with an intensive care episode of two days or more at six Swedish ICUs. The data were analysed using Inductive Content Analysis. FINDINGS: Patient autonomy in intensive care was shown to be 'A trajectory towards partnership in care depending on state of health and mutual understanding'. It was experienced through acknowledged dependence, being recognised as a person, invited participation and becoming a co-partner in care. CONCLUSION: Patients in need of intensive care wanted to be involved in making decisions about their care as this creates a trusting and healthy care environment. Greater awareness is required about the ICU patient not only being a passive care recipient but also an active agent and where involvement in decision-making and participation in care are crucial. PMID- 26279389 TI - Patient and family/friend satisfaction in a sample of Jordanian Critical Care Units. AB - AIM: The aim of the study was to assess the validity of family members/friends as proxies by comparing perceptions of satisfaction with care and decision making between critically ill patients and their family/friends. DESIGN: A comparative, descriptive cross-sectional study. SETTING: Seven Critical Care Units across four public and military hospitals in the centre and southern regions of Jordan. METHODS: A modified version of the Family Satisfaction-ICU (FS-ICU) questionnaire was distributed to Critical Care Unit (CCU) patients before hospital discharge. In addition, up to two family members/close friends were also asked to complete the questionnaire. RESULTS: A total of 213 patients (response rate 72%) and 246 family members/friends (response rate 79%) completed and returned the questionnaire. Although the majority of family members/friends and patients were satisfied with overall care, patients were generally significantly less satisfied (mean (SD) care subscale 75.6 (17.8) and 70.9 (17.3), respectively, (p=0.005). When individual items were examined, significant differences in nursing care (family/friends 80.1 (20.7) versus patient 75.9 (22.2), p=0.038) and inclusion in decision making (family/friends 53.9 (33.2) versus patient 62.0 (34.2), p=0.010) were found. CONCLUSION: The study showed a degree of congruence between patients and their family members/friends in relation to their satisfaction with the CCU experience. Thus, views of family/friends may serve as a proxy in assessing care and decision making processes of critically ill patients. RELEVANCE TO CLINICAL PRACTICE: Appropriate training of the critical care team and provision of strategies to address the concerns of patients' families are needed to improve overall patient satisfaction. PMID- 26279391 TI - Diffuse triple-vessel coronary spasm as a cause of asystole and syncope. AB - Vasospasm plays an important role in the pathogenesis of ischemic heart disease, including unstable angina, myocardial infarction, and sudden death. Coronary artery spasm rarely involves different coronaries in the same time. Three-vessel spasm may be accompanied by ST-segment elevation, lethal arrhythmias, and syncope due to the wide extent of ischemia. In the present case, a patient with syncope secondary to documented diffuse vasospasm involving 3 major coronary arteries was reported. This case report indicated that in case of unexplained syncope, asystole secondary to coronary artery spasm should be considered as a possible cause. PMID- 26279392 TI - The ability of renal ultrasound and ureteral jet evaluation to predict 30-day outcomes in patients with suspected nephrolithiasis. AB - STUDY OBJECTIVE: We sought to identify findings on bedside renal ultrasound that predicted need for hospitalization in patients with suspected nephrolithiasis. METHODS: A convenience sample of patients with suspected nephrolithiasis was prospectively enrolled and underwent bedside ultrasound of the kidneys and bladder to determine the presence and degree of hydronephrosis and ureteral jets. Sonologists were blinded to any other laboratory and imaging data. Patients were followed up at 30 days by phone call and review of medical records. RESULTS: Seventy-seven patients with suspected renal colic were included in the analysis. Thirteen patients were admitted. Reasons for admission included intractable pain, infection, or emergent urologic intervention. All 13 patients requiring admission had hydronephrosis present on initial bedside ultrasound. Patients with moderate hydronephrosis had a higher admission rate (36%) than those with mild hydronephrosis (24%), P<.01. Of patients without hydronephrosis, none required admission within 30 days. The sensitivity and specificity of hydronephrosis for predicting subsequent hospitalization were 100% and 44%, respectively. Loss of the ipsilateral ureteral jet was not significantly associated with subsequent hospital admission and did not improve the predictive value when used in combination with the degree of hydronephrosis. CONCLUSIONS: No patients with suspected renal colic and absence of hydronephrosis on bedside ultrasound required admission within 30 days. Ureteral jet evaluation did not help in prediction of 30-day outcomes and may not be useful in the emergency department management of renal colic. PMID- 26279393 TI - Predictors of patient adherence to follow-up recommendations after an ED visit. AB - BACKGROUND: It is unclear whether factors identified during the emergency department (ED) visit predict noncompliance with ED recommendations. STUDY OBJECTIVE: We sought to determine predictors of adherence to medical recommendations after an ED visit. METHODS: We conducted a prospective, observational study at a single urban medical center. Eligible ED patients provided baseline demographic data as well as information regarding insurance status, whether they had a primary care physician (PCP), and the impact of cost of care on their ability to follow medical recommendations. Patients were contacted at least 1 week after the ED visit and answered questions regarding adherence to medical recommendations. RESULTS: Four hundred twenty-two patients agreed to participate in the study. At follow-up, 89.7% of patients reported that they had complied with recommendations made during the ED visit. Patients who were adherent to follow-up recommendations were more likely to have a primary care provider (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.1-6.1), have an annual income of greater than $35000 (OR, 2.9; 95% CI, 1.2-7.2), and report a non-Hispanic ethnicity or race (OR, 2.8; 95% CI, 1.1-7.1). Individuals who reported that cost "sometimes" or "always" impacts their ability to follow their physician's recommendations were significantly less likely to comply with ED recommendations (OR, 2.7; 95% CI, 1.3-5.6). CONCLUSION: Individuals who reported that cost affects their ability to follow their physician's recommendations and those who did not have a PCP were less likely to follow ED recommendations. Identification of predictors of noncompliance during the ED visit may aid in ensuring compliance with ED recommendations. PMID- 26279394 TI - Xenotransplantation of human adipose-derived stem cells in the regeneration of a rabbit peripheral nerve. AB - Adipose tissue-derived mesenchymal stem cells (AdMSCs) are useful in the regeneration of neural tissues. Furthermore, xenotransplantation of human adipose tissue-derived mesenchymal stem cells (hAdMSCs) into animal models has already been tested and the results encouraged us to study peripheral nerve regeneration in rabbits, in order to test the feasibility of a xenotransplantation of hAdMSCs. ANIMALS AND METHOD: To promote end-to-end nerve fiber contacts of a 4-cm gap in the peroneal nerve of white New Zealand rabbits, an autologous vein conduit was used and three groups of animals were evaluated. In Group I, the gap was repaired with a vein conduit refilled with fibrin. Group II was similar, but the animals were treated with cyclosporine A. In Group III, a fibrin scaffold with hAdMSCs was placed inside the autologous vein conduit, and animals were treated with cyclosporine A. Neurofilament immunohistochemistry results showed 100% nerve regeneration at the vein guidance channel 90 days after the surgery in the hAdMSC transplanted group but lesser neural regeneration in the neurofilaments of groups I and II. The analysis of variance (ANOVA) test showed statistically significant differences among all groups (p < 0.04). Group III exclusively tested positive for human monoclonal anti-mitochondrial antibody. Electron microscopy images showed tiny bundles, with a predominance of nonmyelinated axons. Myelinated axons caused irregular thickness of the myelin sheath, which was especially observed in group III. CONCLUSIONS: Xenotransplantation of hAdMSCs into a fibrin scaffold promoted nerve regeneration through a vein conduit that connected a 4-cm gap created at the peroneal nerve of rabbits. Animals treated with hAdMSCs presented negative inflammatory response at the regenerated nerve gaps, but it was demonstrated that hAdMSCs were incorporated to the new nerve creating neural tissue and endothelial cells. However, hAdMSCs required immunosuppression with cyclosporine A to achieve axonal regeneration. PMID- 26279395 TI - Factors associated with low femoral neck bone mineral density in very elderly Chinese males. AB - OBJECTIVE: This study was designed to identify factors associated with the femoral neck bone mineral density (FNBMD) of the very elderly (aged 80 or more) Chinese males. METHODS: A total of 1177 very elderly Chinese males were recruited into the study, and subjected to FNBMD, biochemical parameters, bone turnover markers, and serum sex steroids assays. Univariate and multivariate regression analyses were performed to identify factors independently related to FNBMD. RESULTS: It was demonstrated that age (beta=-0.003, P=0.035), concomitant chronic obstructive pulmonary disease (COPD, beta=-0.027, P=0.009), serum beta-C telopeptide of type 1 collagen (beta-CTX, beta=-0.097, P<0.001), and parathyroid hormone (PTH, beta=-0.001, P=0.004) were negatively correlated with the FNBMD, while body mass index (BMI, beta=0.009, P<0.001), and serum estradiol (beta=0.001, P=0.038) were positively related to FNBMD in very elderly Chinese males. CONCLUSION: An integrated intervention should be implemented to increase the BMD of the very elderly males, with special attention to preventing and curing COPD, reducing serum beta-CTX and PTH levels, as well as keeping a proper BMI and serum estradiol level. PMID- 26279396 TI - Ghrelin regulates GLP-1 production through mTOR signaling in L cells. AB - Glucagon-like peptide (GLP-1), an intestinal incretin produced in L-cells and released in response to meal intake, functions to promote insulin secretion and to decrease plasma glucose. Ghrelin is an orexigenic hormone critical for glucose homeostasis. The molecular mechanism by which ghrelin alters GLP-1 production remains largely unknown. Here we showed that ghrelin attenuates GLP-1 production through mTOR signaling. In GHSR1a null mice, ileal mTOR signaling, proglucagon and circulating GLP-1 were significantly increased. Antagonism of the GHSR1a by D Lys-3-GHRP-6 increased GLP-1 synthesis and release in STC-1 cells. Treatment of STC-1 cells with ghrelin decreased the production of GLP-1. This effect was associated with a significant inhibition of mTOR signaling. Overexpression of ghrelin inhibited proglucagon promoter activity and GLP-1 production. Inhibition of mTOR activity by mTOR siRNA blocked D-Lys-3-GHRP-6 induced GLP-1 production in STC-1 cells. Our results suggest that mTOR signaling mediates the inhibitory effect of ghrelin on GLP-1 production. PMID- 26279397 TI - Piezotronic-Enhanced Photoelectrochemical Reactions in Ni(OH)2-Decorated ZnO Photoanodes. AB - Controlling the interface electronic band structure in heterostructures is essential for developing highly efficient photoelectrochemical (PEC) photoanodes. Here, we presented an enhanced oxygen evolution reaction (OER) by introducing the piezotronics concept, i.e., piezoelectric polarization (Ppz)-induced band engineering. In a Ni(OH)2-decorated ZnO photoanode system, appreciably improved photocurrent density of sulfite (SO3(2-)) and hydroxyl (OH(-)) oxidation reactions were obtained by physically deflecting the photoanode. Both theoretical and experimental results suggested that the performance enhancement was a result of the piezoelectric Ppz-endowed enlargement of the built-in electric field at the ZnO/Ni(OH)2 interface, which could drive an additional amount of photoexcited charges from ZnO toward the interface for OER. This strategy demonstrates a new route for improving the performance of inexpensive catalysts-based solar-to-fuel production. PMID- 26279398 TI - Chiral dopants and the twist-bend nematic phase--induction of novel mesomorphic behaviour in an apolar bimesogen. AB - Herein we report studies on a bimesogen that exhibits a chiral twist bend nematic phase when doped with small weight percentages of a chiral material and a partial phase diagram constructed. At low concentrations a wide temperature range blue phase is observed, whereas at higher concentrations an additional 'nematic-like' mesophase was discovered at a lower temperature than the twist-bend nematic phase. In addition to an apparent isotropic-"isotropic" transition, the doped materials also exhibited a weakly birefringent phase upon annealing in the isotropic liquid phase, implying pretransitional behaviour in the same vein as that seen for TGB phases. When confined in a planar aligned cell, the NTB phase exhibited two domains that alternated between light and dark with rotation of the sample stage, as well as the application of an external electric field. Upon the addition of a chiral dopant one of these domains was eliminated, leading to their assignment as twist domains of opposite handedness. PMID- 26279399 TI - Intracellular expression profile and clinical significance of the CCR9-CCL25 chemokine receptor complex in nasopharyngeal carcinoma. AB - OBJECTIVES: This study aimed to investigate the association of C-C chemokine receptor type 9 (CCR9) and C-C motif chemokine 25 (CCL25) expression levels with clinical and tumour-node-metastasis stage in nasopharyngeal carcinoma. METHODS: A total of 42 nasopharyngeal carcinoma patients (nasopharyngeal carcinoma group) and 18 patients with a normal nasopharynx (control group) were included in this study. Tissues were collected during surgery and medical examinations. The CCR9 and CCL25 messenger RNA and protein levels were measured using quantitative reverse transcription polymerase chain reaction, Western blotting and immunohistochemical analysis. RESULTS: CCR9 and CCL25 messenger RNA and protein levels were significantly increased in the nasopharyngeal carcinoma group compared with the control group (p < 0.05). Both CCR9 and CCL25 messenger RNA and protein levels were significantly higher in advanced-stage nasopharyngeal carcinoma (stages III and IV) patients compared with early-stage nasopharyngeal carcinoma (stages I and II) patients (p < 0.05). CONCLUSION: The extent of CCR9 and CCL25 upregulation in nasopharyngeal carcinoma correlates with the tumour node-metastasis stage. PMID- 26279401 TI - Using data sources beyond PubMed has a modest impact on the results of systematic reviews of therapeutic interventions. AB - OBJECTIVES: Searching multiple sources when conducting systematic reviews is considered good practice. We aimed to investigate the impact of using sources beyond PubMed in systematic reviews of therapeutic interventions. STUDY DESIGN AND SETTING: We randomly selected 50 Cochrane reviews that searched the PubMed (or MEDLINE) and EMBASE databases and included a meta-analysis of >=10 studies. We checked whether each eligible record in each review (n = 2,700) was retrievable in PubMed and EMBASE. For the first-listed meta-analysis of >=10 studies in each review, we examined whether excluding studies not found in PubMed affected results. RESULTS: A median of one record per review was indexed in EMBASE but not in PubMed; a median of four records per review was not indexed in PubMed or EMBASE. Meta-analyses included a median of 13.5 studies; a median of zero studies per meta-analysis was indexed in EMBASE but not in PubMed; a median of one study per meta-analysis was not indexed in PubMed or EMBASE. Meta-analysis using only PubMed-indexed vs. all available studies led to a different conclusion in a single case (on the basis of conventional criteria for statistical significance). In meta-regression analyses, effects in PubMed- vs. non-PubMed indexed studies were statistically significantly different in a single data set. CONCLUSION: For systematic reviews of the effects of therapeutic interventions, gains from searching sources beyond PubMed, and from searching EMBASE in particular are modest. PMID- 26279402 TI - Re: "Zinc lozenges and vitamin C for the common cold are not examples of placebo effect in action". PMID- 26279400 TI - Assessment of vibration of effects due to model specification can demonstrate the instability of observational associations. AB - OBJECTIVES: Model specification-what adjusting variables are analytically modeled may influence results of observational associations. We present a standardized approach to quantify the variability of results obtained with choices of adjustments called the "vibration of effects" (VoE). STUDY DESIGN AND SETTING: We estimated the VoE for 417 clinical, environmental, and physiological variables in association with all-cause mortality using National Health and Nutrition Examination Survey data. We selected 13 variables as adjustment covariates and computed 8,192 Cox models for each of 417 variables' associations with all-cause mortality. RESULTS: We present the VoE by assessing the variance of the effect size and in the -log10(P-value) obtained by different combinations of adjustments. We present whether there are multimodality patterns in effect sizes and P-values and the trajectory of results with increasing adjustments. For 31% of the 417 variables, we observed a Janus effect, with the effect being in opposite direction in the 99th versus the 1st percentile of analyses. For example, the vitamin E variant alpha-tocopherol had a VoE that indicated higher and lower risk for mortality. CONCLUSION: Estimating VoE offers empirical estimates of associations are under different model specifications. When VoE is large, claims for observational associations should be very cautious. PMID- 26279403 TI - Public titles of clinical trials should have ethics review. AB - A key aspect to guarantee that research with human subjects is ethical is being overlooked. Ethics review committees invest great effort examining the informed consent documents of research protocols to ensure that potential participants can provide consent validly and are not deluded into thinking that the experimental intervention they may sign up for is already known to be therapeutic. However, these efforts to avoid what is called the "therapeutic misconception" might be in vain if the title with which the studies are being introduced to the potential participants escapes ethics review. Research participants might be deceived by clinical trials entitled "novel therapy" when the point of the trial is precisely to find out whether the intervention at stake is therapeutic or not. Providing potential research participants with such misleading information hampers their ability to make informed decisions. The well-established scrutiny that ethics review committees exercise with regard to consent forms is limited if the registration of clinical trials, for which a public title is chosen, constitutes a process that is independent from the ethics review. In this article, we examine this problem, assess recent measures to integrate clinical trial registration with ethics review processes, and provide specific recommendations to solve the problem and ultimately enhance the accountability, transparency, and ethics of research with human subjects. PMID- 26279404 TI - Human genes with a greater number of transcript variants tend to show biological features of housekeeping and essential genes. AB - Alternative splicing is a process observed in gene expression that results in a multi-exon gene to produce multiple mRNA variants which might have different functions and activities. Although physiologically important, many aspects of genes with different number of transcript variants (or splice variants) still remain to be characterized. In this study, we provide bioinformatic evidence that genes with a greater number of transcript variants are more likely to play functionally important roles in cells, compared with those having fewer transcript variants. Among 21,983 human genes, 3728 genes were found to have a single transcript, and the remaining genes had 2 to 77 transcript variants. The genes with more transcript variants exhibited greater frequencies of acting as housekeeping and essential genes rather than tissue-selective and non-essential genes. They were found to be more conserved among 64 vertebrate species as orthologs, subjected to regulations by transcription factors and microRNAs, and showed hub node-like properties in the human protein-protein interaction network. These findings were also confirmed by metabolic simulations of 60 cancer metabolic models. All these results indicate that genes with a greater number of transcript variants play biologically more fundamental roles. PMID- 26279405 TI - Enhancing Anger Perception With Transcranial Alternating Current Stimulation Induced Gamma Oscillations. AB - BACKGROUND: In recent years a variety of neuroimaging studies have highlighted a role of neural oscillations in perception and cognition. However, surprisingly little is known about oscillatory activity underlying facial emotion perception. The limited number of studies that have addressed this question indicate that gamma oscillations are one mechanism underlying this process. OBJECTIVE: The present study aimed to further elucidate the role of neural oscillations within the gamma range in facial emotion perception in healthy adults by using transcranial alternating current stimulation (tACS). METHODS: To that effect we carried out three experiments with separate groups of participants using tACS to modulate occipital oscillations while participants completed facial anger and facial identity tasks. RESULTS: The results of these experiments indicated that modulating occipital gamma with 40 Hz tACS enhances facial anger perception. CONCLUSION: This finding implicates an important role of occipital gamma oscillations in facial emotion perception. PMID- 26279406 TI - Increased Reliance on Value-based Decision Processes Following Motor Cortex Disruption. AB - BACKGROUND: During motor decision making, the neural activity in primary motor cortex (M1) encodes dynamically the competition occurring between potential action plans. A common view is that M1 represents the unfolding of the outcome of a decision process taking place upstream. Yet, M1 could also be directly involved in the decision process. OBJECTIVE: Here we tested this hypothesis by assessing the effect of M1 disruption on a motor decision-making task. METHODS: We applied continuous theta burst stimulation (cTBS) to inhibit either left or right M1 in different groups of subjects and included a third control group with no stimulation. Following cTBS, participants performed a task that required them to choose between two finger key-presses with the right hand according to both perceptual and value-based information. Effects were assessed by means of generalized linear mixed models and computational simulations. RESULTS: In all three groups, subjects relied both on perceptual (P < 0.0001) and value-based information (P = 0.003) to reach a decision. Yet, left M1 disruption led to an increased reliance on value-based information (P = 0.03). This result was confirmed by a computational model showing an increased weight of the valued based process on the right hand finger choices following left M1 cTBS (P < 0.01). CONCLUSION: These results indicate that M1 is involved in motor decision making, possibly by weighting the final integration of multiple sources of evidence driving motor behaviors. PMID- 26279407 TI - Left Dorsolateral Prefrontal Cortex Anodal tDCS Effects on Negative Symptoms in Schizophrenia. PMID- 26279409 TI - Risk Factors for Postoperative Intra-Abdominal Abscess after Laparoscopic Appendectomy: Analysis for Consecutive 1,817 Experiences. AB - BACKGROUND: Possible risk factors for postoperative intra-abdominal abscess (IAA) formation after laparoscopic appendectomy (LA) remain controversial. A perforated appendicitis, diabetes mellitus, peritoneal irrigation, obesity and age are considered to be possible risk factors for postoperative IAA, but the existing evidence is insufficient. This study aimed to identify the risk factors for IAA formation in patients receiving LA. METHODS: Between January 2010 and December 2013, 1,817 patients who underwent 3-port LA were enrolled in this study. Patients were classified into 2 groups according to the development of postoperative IAA, and the differences between the groups were analyzed. RESULTS: The incidence of IAA after LA was 1.5%, and the only identified risk factor for IAA was peritoneal irrigation. On logistic regression analysis of those patients who received peritoneal irrigation, suppurative appendicitis and non-placement of the peritoneal drain were found to be significant risk factors for the development of IAA. CONCLUSIONS: Peritoneal irrigation in a case of abdomen contamination was shown to be a risk factor for the development of postoperative IAA after LA. When peritoneal irrigation is performed, surgeons should consider using peritoneal drainage and postoperative antibiotics (including anti-anaerobic antibiotics) to prevent postoperative IAA formation. PMID- 26279408 TI - The Homeostatic Interaction Between Anodal Transcranial Direct Current Stimulation and Motor Learning in Humans is Related to GABAA Activity. AB - BACKGROUND: The relative timing of plasticity-induction protocols is known to be crucial. For example, anodal transcranial direct current stimulation (tDCS), which increases cortical excitability and typically enhances plasticity, can impair performance if it is applied before a motor learning task. Such timing dependent effects have been ascribed to homeostatic plasticity, but the specific synaptic site of this interaction remains unknown. OBJECTIVE: We wished to investigate the synaptic substrate, and in particular the role of inhibitory signaling, underpinning the behavioral effects of anodal tDCS in homeostatic interactions between anodal tDCS and motor learning. METHODS: We used transcranial magnetic stimulation (TMS) to investigate cortical excitability and inhibitory signaling following tDCS and motor learning. Each subject participated in four experimental sessions and data were analyzed using repeated measures ANOVAs and post-hoc t-tests as appropriate. RESULTS: As predicted, we found that anodal tDCS prior to the motor task decreased learning rates. This worsening of learning after tDCS was accompanied by a correlated increase in GABAA activity, as measured by TMS-assessed short interval intra-cortical inhibition (SICI). CONCLUSION: This provides the first direct demonstration in humans that inhibitory synapses are the likely site for the interaction between anodal tDCS and motor learning, and further, that homeostatic plasticity at GABAA synapses has behavioral relevance in humans. PMID- 26279410 TI - Use of rotational angiography in assessing relationship of the airway to vasculature during cardiac catheterization. AB - OBJECTIVES: We are the first to describe the use of three-dimensional rotational angiography (3DRA) in creating multiplanar reconstruction (MPR) and volume rendering, in the catheterization suite, of airways at risk for compression by adjacent cardiac structures. BACKGROUND: 3DRA has emerged as a promising tool for improved visualization of cardiac and vascular structures in congenital heart disease. METHODS: This is a retrospective review of all available cases at our institution in which MPR from 3DRA was used to assess airways in relation to surrounding cardiovascular structures. RESULTS: Eight cases were reviewed from January 1, 2011 to November 30, 2013. Seven children had complex biventricular anatomy, including repaired truncus arteriosus, repaired absent pulmonary valve, repaired double outlet right ventricle, and vascular rings. One child had double inlet left ventricle and had undergone a hybrid procedure (stenting of the patent ductus arteriosus and banding of bilateral pulmonary arteries) before the Glenn procedure. Six of these cases involved distortion or stenosis of the pulmonary conduit or branch pulmonary arteries. In all cases, the trachea and the main bronchi were clearly visualized using MPR. Management was affected by the visualization of the airways during the catheterization procedure in seven of eight cases. Four cases had intraprocedural bronchoscopy that confirmed airway findings seen by MPR. In one case, computed tomography confirmed left bronchial compression seen by MPR. CONCLUSIONS: 3DRA can visualize airway anatomy and its relationship to the vasculature accurately. This has significant implications for preinterventional planning, intraprocedural management, as well as postprocedural recovery. PMID- 26279411 TI - Comparison between transdermal nitroglycerin and sildenafil citrate in intrauterine growth restriction: effects on uterine, umbilical and fetal middle cerebral artery pulsatility indices. AB - OBJECTIVES: To evaluate the effects of transdermal nitroglycerin (GTN) and sildenafil citrate on Doppler velocity waveforms of the uterine (UtA), umbilical (UA) and fetal middle cerebral (MCA) arteries in pregnancies with intrauterine growth restriction (IUGR). METHODS: This was a prospective study of 35 singleton pregnancies (gestational age, 24-31 weeks) with IUGR and abnormal UtA and UA Doppler waveforms. We compared maternal arterial blood pressure and Z-scores of the pulsatility index (PI) of UtA, UA and fetal MCA before and after application of a transdermal GTN patch (average dose, 0.4 mg/h), oral sildenafil citrate (50 mg) or placebo. Statistical analysis was performed by ANOVA for paired samples. RESULTS: There was a significant decrease in UtA-PI after application of GTN (21.0%) and sildenafil citrate (20.4%). A significant reduction in UA-PI was also observed for both GTN (19.1%) and sildenafil citrate (18.2%). There was no difference in UtA- and UA-PI when the GTN and sildenafil groups were compared. No changes in Doppler velocimetry were observed in the placebo group and no significant change in MCA-PI was observed in any group. Maternal arterial blood pressure decreased with administration of both GTN and sildenafil citrate in those with pre-eclampsia. CONCLUSION: The use of transdermal GTN or sildenafil citrate in pregnancies with IUGR is associated with a significant reduction in both UtA and UA Doppler PI, as well as maternal arterial blood pressure. Neither drug affected the MCA-PI. Copyright (c) 2015 ISUOG. Published by John Wiley & Sons Ltd. PMID- 26279412 TI - Insights into the growth of bismuth nanoparticles on 2D structured BiOCl photocatalysts: an in situ TEM investigation. AB - The synthetic techniques for novel photocatalytic crystals had evolved by a trial and-error process that spanned more than two decades, and an insight into the photocatalytic crystal growth process is a challenging area and prerequisite for achieving an excellent photoactivity. Bismuth nanoparticle based hybrids, such as Bi/BiOCl composites, have recently been investigated as highly efficient photocatalytic systems because of the localized surface plasmon resonance (LSPR) of nanostructured bismuth. In this work, the observation towards the formation and growth of bismuth nanoparticles onto 2D structured BiOCl photocatalysts has been performed using a transmission electron microscope (TEM) directly in real time. The growth of bismuth nanoparticles on BiOCl nanosheets can be emulated and speeded up driven by the electron beam (e(-) beam) in TEM. The crystallinity, growth and the elemental evolution during the formation of bismuth nanoparticles have also been probed in this work. PMID- 26279413 TI - Waist:height ratio, waist circumference and metabolic syndrome abnormalities in Colombian schooled adolescents: a multivariate analysis considering located adiposity. AB - Very few large studies in Latin America have evaluated the association between waist:height ratio (W-HtR) and cardiometabolic risk in children and adolescents. Further, multivariable analyses verifying the independence of located subcutaneous fat have not been conducted so far. The aim of this study was to evaluate the associations of W-HtR and waist circumference (WC) with metabolic syndrome abnormalities and high LDL-cholesterol levels in schooled adolescents before and after adjusting for trunk skinfolds and BMI. The sample consisted of 831 boys and 841 girls aged 10-17 years. Biochemical, blood pressure and anthropometrical variables were measured. Age- and sex-specific quartiles of W HtR and WC were used in Poisson regression models to evaluate the associations. High WC values (highest quartile v. quartiles 1-3) were associated with high TAG levels in both sexes (prevalence ratio, boys: 2.57 (95 % CI 1.91, 3.44); girls: 1.92 (95 % CI 1.49, 2.47); P0.05). High W-HtR (highest quartile v. quartiles 1-3) was only independently associated with high TAG in female adolescents (1.99 (95 % CI 1.55, 2.56); P<0.05). In conclusion, WC showed better association with cardiometabolic risk than W-HtR in the children of this study. This observation does not support W-HtR as a relevant adiposity marker for cardiovascular and metabolic risk in adolescence. PMID- 26279414 TI - General Erectile Functioning among Young, Heterosexual Men Who Do and Do Not Report Condom-Associated Erection Problems (CAEP). AB - INTRODUCTION: Condom-associated erection problems (CAEP) are an underestimated factor related to inconsistent or incomplete male condom use. The underlying mechanisms of CAEP are not understood, and whether men who report these difficulties are also likely to experience erectile problems in situations when condoms are not used has not been studied. AIM: The aim of the study was to investigate, in a sample of condom-using young, heterosexual men (aged 18-24 years), whether men who report CAEP are more likely to (i) have erection problems when not using condoms and (ii) meet criteria for erectile dysfunction. METHODS: A total of 479 men recruited online completed the International Index of Erectile Function (IIEF-5) and answered questions about erection problems experienced when using and not using condoms during the last 90 days. Demographic, sexual experience, and health status variables were investigated as correlates. MAIN OUTCOME MEASURES: Self-reported frequency of erection loss during condom application or during penile-vaginal intercourse (PVI) in the past 90 days and IIEF-5 scores. RESULTS: Of the men, 38.4% were classified in the no CAEP group, 13.8% as having CAEP during condom application, 15.7% as having CAEP during PVI, and 32.2% as having CAEP during both condom application and PVI. Men reporting any form of CAEP were significantly more likely than men reporting no CAEP to also report erection difficulties during sexual activity when not using condoms. Men who reported CAEP during PVI only or during both application and PVI scored significantly lower on the IIEF-5 than men without CAEP. CONCLUSION: The findings suggest that men who report CAEP are also more likely to experience more generalized erection difficulties. Clinicians should assess whether men using condoms experience CAEP and where appropriate, refer for psychosexual therapy or provide condom skills education. PMID- 26279415 TI - Fine-Needle Aspiration Cytology of Metastatic Plasmacytoid Urothelial Carcinoma: Report of Four Cases Including a Case of Mixed Plasmacytoid and Micropapillary Morphology. AB - OBJECTIVES: The aim of this study was to report a small series of fine-needle aspiration (FNA) cytology of the plasmacytoid variant of urothelial carcinoma (PVUC). STUDY DESIGN: A computerized search of our laboratory information system was performed for the 5-year period between January 2008 and January 2013 to identify all FNA cases in which the corresponding surgical pathology cases were diagnosed as PVUC. RESULTS: The 4 cases identified were from 2 men (aged 56 and 64 years) and 2 women (aged 72 and 46 years). The FNA smears demonstrated low-to moderate cellularity and consisted predominantly of single and dyshesive, medium sized tumor cells with eccentrically located nuclei and a moderate-to-abundant dense cytoplasm. The nuclei were oval with slightly irregular nuclear membranes and contained coarse granular chromatin with inconspicuous or small nucleoli. There was moderate nuclear variation in size. The nuclear-to-cytoplasmic ratio ranged from <1 to 3. Binucleation, cytoplasmic vacuoles, and perinuclear hof were occasionally seen. CONCLUSIONS: FNA cytology of PVUC shares features with plasma cell neoplasms, lobular carcinoma of the breast, and signet ring cell carcinoma of the stomach. Being aware of the patient's clinical history and the potential diagnostic pitfall of this rare variant of urothelial carcinoma is important for an accurate diagnosis on FNA biopsy. PMID- 26279416 TI - Renal Tumor in Pregnancy: A Case Report and Review of the Literature. AB - The authors present their renal tumor cases observed during pregnancy and review the literature related to this topic. Between January 1, 2000 and January 1, 2015, altogether 3 patients were treated for renal tumor during pregnancy. Two of them had surgery performed during pregnancy, while in the other, premature birth of the baby preceded surgery. In the first case, a laparoscopic tumor resection was performed in the 29th week of the patient's pregnancy. In the second case, a transperitoneal radical nephrectomy was carried out during the 10th week of pregnancy. In the case of the third patient, a caesarean section was performed during the 32nd week of gestation, and then followed later by surgery for the metastatic renal tumor. However, the tumor was found to be inoperable. PMID- 26279417 TI - Could MicroRNAs be Regulators of Gout Pathogenesis? AB - MicroRNAs (miRNAs) are a class of noncoding RNAs that mainly negatively regulate gene expression. miRNAs have important roles in many diseases, including inflammatory diseases. Gout is a common arthritis caused by deposition of monosodium urate crystals within joints. Recent studies suggested that miRNAs may be involved in the development of inflammatory arthritis, including acute gouty arthritis. In the present review, we systemically discuss relevant publications in order to provide a better understanding on the possible role of miRNAs in gout. miRNAs may act as regulators of gout pathogenesis via several pathways. Targeting miRNAs may be a promisingstrategy in the treatment of gout. PMID- 26279418 TI - Transcription Factor Egr1 is Involved in High Glucose-Induced Proliferation and Fibrosis in Rat Glomerular Mesangial Cells. AB - Backgroud: Diabetic nephropathy is one of the most frequent causes of end-stage renal disease and is associated with proliferation of glomerular mesangial cells (MCs) and excessive production of the extracellular matrix (ECM). Several studies have shown that early growth response factor 1 (Egr1) plays a key role in renal fibrosis by regulating the expression of genes encoding ECM components. However, whether Egr1 also contributes to diabetic nephropathy is unclear. METHODS: In the present study, we compared the expression of Egr1 in kidneys from OLETF rats with spontaneous type 2 diabetes and healthy LETO rats. We also examined whether high glucose and TGF-beta1 signaling up-regulated Egr1 expression in cultured MCs, and whether Egr1 expression influenced MC proliferation and expression of ECM genes. RESULTS: We found that higher expression of Egr1 and TGF-beta1, at both the mRNA and protein levels, the kidneys from OLETF rats vs. LETO rats. High glucose or TGF-beta1 signaling rapidly up-regulated expression of Egr1 mRNA and protein in cultured MCs. Overexpressing Egr1 in MCs by transfection with M61-Egr1 plasmid or treatment with high glucose up-regulated expression of fibronectin, type IV collagen and TGF-beta1, and promoted MC proliferation. Conversely, siRNA-mediated silencing of Egr1 expression down-regulated these genes and inhibited MC proliferation. Chromatin immunoprecipitation (ChIP) assays revealed that Egr1 bound to the TGF-beta1 promoter. CONCLUSION: Our results provide strong evidence that Egr1 contributes to diabetic nephropathy by enhancing MC proliferation and ECM production, in part by interacting with TGF-beta1. PMID- 26279419 TI - Human Chorionic Gonadotropin Protects Vascular Endothelial Cells from Oxidative Stress by Apoptosis Inhibition, Cell Survival Signalling Activation and Mitochondrial Function Protection. AB - BACKGROUND/AIM: Previous reports have made it hypothetically possible that human chorionic gonadotropin (hCG) could protect against the onset of pregnancy-related pathological conditions by acting as an antioxidant. In the present study we planned to examine the effects of hCG against oxidative stress in human umbilical vein endothelial cells (HUVEC). METHODS: HUVEC were subjected to peroxidation by hydrogen peroxide. The modulation of nitric oxide (NO) release by hCG and its effects on cell viability, glutathione (GSH) levels, mitochondrial membrane potential and mitochondrial transition pore opening (MPTP) were examined by specific dyes. Endothelial and inducible NO synthase (eNOS and iNOS), Akt and extracellular -signal-regulated kinases 1/2 (ERK1/2) activation and markers of apoptosis were analyzed by Western Blot. RESULTS: In HUVEC, hCG reduced NO release by modulating eNOS and iNOS. Moreover, hCG protected HUVEC against oxidative stress by preventing GSH reduction and apoptosis, by maintaining Akt and ERK1/2 activation and by keeping mitochondrial function. CONCLUSION: The present results have for the first time shown protective effects exerted by hCG on vascular endothelial function, which would be achieved by modulation of NO release, antioxidant and antiapoptotic actions and activation of cell survival signalling. These findings could have clinical implications in the management of pregnancy-related disorders. PMID- 26279420 TI - Sodium Ferulate Prevents Daunorubicin--Induced Apoptosis in H9c2 Cells via Inhibition of the ERKs Pathway. AB - BACKGROUND: Daunorubicin (DNR)-induced cardiotoxicity, which is closely associated with cardiomyocyte apoptosis, limits the drug's clinical application. The activation of the extracellular regulated protein kinases (ERKs) pathway is responsible for the pro-apoptosis effect of DNR Sodium ferulate (SF) has recently been found to attenuate both DNR-induced cardiotoxicity and mitochondrial apoptosis in juvenile rats. Nonetheless, the precise mechanism underlying SF induced cardio-protection remains unclear. METHODS: The DNR-injured H9c2 cell model was prepared by incubating the cells in 1 uM DNR for 24 h. Amounts of 15.6, 31.3 or 62.5 uM SF were simultaneously added to the cells. The effect of SF on the cytotoxic and apoptotic parameters of the cells was studied by monitoring apoptosis regulation via the ERKs pathway. RESULTS: SF attenuated DNR-induced cell death (particularly apoptotic death), cTnI and beta-tubulin degradation, and cellular morphological changes. SF reduced mitochondrial membrane potential depolarization, cytochrome c leakage, and caspase-9 and caspase-3 activation. SF also decreased ERK1/2, phospho-ERK1/2, p53 and Bax expression and increased Bcl-2 expression. These effects were similar to the results observed when using the pharmacological ERKs phosphorylation inhibitor, AZD6244. CONCLUSION: We determined that SF protects H9c2 cells from DNR-induced apoptosis through a mechanism that involves the interruption of the ERKs signaling pathway. PMID- 26279421 TI - RP105 Protects Against Apoptosis in Ischemia/Reperfusion-Induced Myocardial Damage in Rats by Suppressing TLR4-Mediated Signaling Pathways. AB - BACKGROUND: Myocardial apoptosis is heavily implicated in the myocardial damage caused by ischemia-reperfusion (I/R). Toll-like receptor 4 (TLR4) is a potent inducer of these apoptotic cascades. In contrast, the radioprotective 105 kDa protein (RP105) is a specific negative regulator of TLR4 signaling pathways. However, the precise mechanisms by which RP105 inhibits myocardium apoptosis via TLR4-associated pathways during I/R is not fully understood. METHODS: We utilized a rat model of myocardial ischemic reperfusion injury (MIRI). Animals were pre treated with Ad-EGFP adenovirus, Ad-EGFP-RP105 adenovirus, saline, or nothing (sham). After three days, rats underwent a 30min left anterior descending coronary artery occlusion and a 4h reperfusion. Mycardial tissue was assessed by immunohistochemistry, TUNEL-staining, Western blot, quantitative RT-PCR, and a morphometric assay. RESULTS: RP105 overexpression resulted in a reduction in infarct size, fewer TUNEL-positive cardiomyocytes, and a reduction in mitochondrial-associated apoptosis cascade activity. Further, RP105 overexpression repressed I/R-induced myocardial injury by attenuating myocardial apoptosis. This was mediated by inhibiting TLR4 activation and the phosphorylation of P38MAPK and the downstream transcription factor AP-1. CONCLUSION: RP105 overexpression leads to the de-activation of TLR4, P38MAPK, and AP-1 signaling pathways, and subsequently represses apoptotic cascades and ensuing damage of myocardial ischemic reperfusion. These findings may become the basis of a novel therapeutic approach for reducing of cardiac damage caused by MIRI. PMID- 26279422 TI - Moderate Hypoxia Down-Regulates Interleukin-6 Secretion and TLR4 Expression in Human Sw.71 Placental Cells. AB - BACKGROUND/AIMS: The placenta is a vital organ for pregnancy. Many in vitro placental experiments are conducted under 21% O2; however, O2 tension could influence cellular functions, including cytokine secretion. We investigated the effects of oxygen tension between moderate hypoxia (5% O2) and normoxia (21% O2) by testing the hypothesis that moderate hypoxia regulates cellular phenotypes differently from normoxia in human trophoblast cells. METHODS AND RESULTS: Sw.71 trophoblast cells were incubated under normoxic or moderately hypoxic conditions. Cells were also treated with lipopolysaccharide (LPS) as a Toll-like receptor 4 (TLR4) ligand inducing inflammation. Interleukin-6 (IL-6) as an inflammatory cytokine was determined, and TLR4, hypoxia-induced factor-1alpha (HIF1alpha), and reactive oxygen species (ROS) production were detected. Moderate hypoxia increased HIF1alpha expression and cell proliferation and acted by two different mechanisms to decrease IL-6 secretion compared with normoxia: it limits the TLR4 expression and ROS production. Treatment with cobalt chloride as an HIF1 activator inhibited IL-6 secretion and TLR4 expression; this effect was reversed on treatment with PX-12 as an HIF1 suppressor. CONCLUSION: IL-6 secretion, TLR4 expression, and ROS production, classical markers of inflammation, are down regulated by moderate hypoxia, and HIF1alpha and ROS have a potential to regulate these responses in human trophoblast cells. PMID- 26279423 TI - B10 Cells Ameliorate the Progression of Lupus Nephritis by Attenuating Glomerular Endothelial Cell Injury. AB - BACKGROUND/AIM: B10 cells are generally considered to inhibit the kidney injury in systemic lupus erythematosus (SLE) mouse models, but recently this function of B10 cells was denied by the lineage-specific deletion of IL-10 from B cells. Thus, this study aimed to determine whether and how B10 cells play a protective role in lupus nephritis (LN). METHODS: LN and non-LN SLE patients without receiving any treatments were recruited, and the percentages of circulating B10 cell were determined. Furthermore, the purified B10 cells were transferred into MRL/lpr SLE mice, and the exact effects of B10 cells on LN progression were investigated. RESULTS: The percentage of circulating B10 cells was significantly higher in patient than in healthy controls, while they were fewer in LN patients than non-LN SLE patients. Moreover, B10 cells rather than plasma IL-10 levels were negatively correlated with disease severity especially with kidney injury in LN patients. In animal experiments, the glomerular injuries including the proteinuria and pathological scores were significantly attenuated in SLE mice transferred with B10 cells, accompanied by the decreased glomerular endothelial cell CD54/CD106 expression, and glomerular p38 phosphorylation as well as increased SOCS3 expression. At the same time, the serum anti-dsDNA autoantibody, TNF-alpha and IFN-gamma levels were also reduced, while there were no changes in serum IL-10 and IL-17 levels in B10 cell transferred mice. CONCLUSION: These findings suggest that B10 cells could - independent from IL-10 - ameliorate glomerular injury in LN through protection of glomerular endothelial cells. PMID- 26279424 TI - Tempol, a Superoxide Dismutase-Mimetic Drug, Ameliorates Progression of Renal Disease in CKD Mice. AB - BACKGROUND: Oxidative stress has been implicated in the pathogenesis of chronic kidney disease (CKD) and antioxidants may ameliorate disease progression. We investigate the beneficial effect of Tempol, a superoxide dismutase-mimetic drug, on progression of disease in a mouse model of CKD. METHODS: CKD was surgically induced in c57BL/6 mice by 5/6 nephrectomy. Mice were randomly divided into 3 groups: sham group, 5/6 nephrectomized group (Nx) and Nx+Tempol (2 mmol/l in drinking water). Mice were sacrificed at the end of 12 weeks. Renal function, structure as well as expression of key molecules involved in the pathogenesis of inflammation, fibrosis and progression in mice were measured. RESULTS: Reduced body weight and impaired renal function (elevation on serum creatinine, blood urea nitrogen, urine albumin, segmental sclerosis and tubulointerstitial damage) was demonstrated in Nx mice but was significantly improved by Tempol administration. Nx animals exhibited significantly elevated proinflammatory and profibrotic factors, activation of NF-kappaB, increased expression of NADPH oxidase related subunits (p47phox, p67phox, gp91phox), and elevated activation of TGF-beta/Smad3, EGFR, MAPK signaling pathway. Tempol inhibited NF-kappaB mediated inflammation, TGF-beta/Smad3-induced renal fibrosis as well as EGFR and MAPK signaling pathway activation. CONCLUSIONS: Tempol administration attenuated renal injury in CKD mice through NF-kappaB, TGF-beta/Smad3, redox-senstive EGFR activation and c-Raf/MEK/ERK pathways. PMID- 26279425 TI - Heat Shock Protein 70 and CHIP Promote Nox4 Ubiquitination and Degradation within the Losartan Antioxidative Effect in Proximal Tubule Cells. AB - BACKGROUND: Angiotensin II/Angiotensin II type 1 receptor (AT1R) effects are dependent on ROS production stimulated by NADPH oxidase activation. Hsp70 regulates a diverse set of signaling pathways through their interactions with proteins. CHIP is a E3 ubiquitin ligase that targets proteins for polyubiquitination and degradation. AIM: We study whether Hsp70/CHIP contribute to the negative regulation of Nox4 after AT1R blockage. METHODS/RESULTS: Primary culture of proximal tubule epithelial cells (PTCs) from SHR and WKY were stimulated with Angiotensin II (AII) or treated with Losartan (L) or Losartan plus Angiotensin II (L+AII). Losartan decreased AT1R and Nox4 while enhancing caveolin-1 and Hsp70 protein expression in SHR PTCs. Immunoprecipitation and immunofluorescence proved interaction and colocalization of increased Hsp70/CHIP with decreased Nox4 in SHR PTCs (L) vs (All). Hsp72 knockdown resulted in enhanced Nox4 protein levels, NADPH oxidase activity and ROS generation in (L+AII) revealing that Losartan was unable to abrogate AII effects on Nox4 expression and oxidative activity. Moreover, MG132 exposed PTCs (L) demostrated blocked ubiquitinated Nox4 degradation and increased colocalization of Nox4/Ubiquitin by inmunofluorescence. Conversely, Hsp72 depletion reduced Nox4/Ubiquitin colocalization causing Nox4 upregulation due to proteosomal degradation inhibition, although Losartan treatment. CONCLUSION: Our study demonstrates that Hsp70 and CHIP mediates the ubiquitination and proteasomal degradation of Nox4 as part of the antioxidative effect of Losartan in SHR. PMID- 26279426 TI - Interleukin-1beta Promotes Epithelial-Derived Alveolar Elastogenesis via alphavbeta6 Integrin-Dependent TGF-beta Activation. AB - BACKGROUND/AIMS: IL-1beta creates persistent pulmonary inflammation accompanied by elevated transforming growth factor beta (TGF-beta levels and is associated with abnormal elastogenesis, which is observed in bronchopulmonary dysplasia (BPD). Although progress has been made in this field, the mechanisms underlying this process remain only partially understood. METHODS: We assessed aberrant elastin localization-associated signaling in mouse pups exposed to 85% O2 treated with either IL-1Ra or 1D11, using morphometric analyses, quantitative RT-PCR, immunostaining, and ELISA. We also evaluated the derivation of elastin-producing cells using dual marker tracking. The regulatory mechanisms of IL-1beta were investigated in vitro in lung epithelial and mesenchymal cells. RESULTS: Elevated levels of IL-1beta, alphavbeta6 and TGF-beta1 were each associated with aberrant elastin production in O2-exposed lungs. IL-1Ra abolished TGF-beta1 activation and alphavbeta6 upregulation, which occurred as a result of exposure to hyperoxia, whereas 1D11 had no discernible effect on the expression of either alphavbeta6 or IL-1beta even following O2-exposure, suggesting that IL-1beta was initially induced. Additionally, double staining revealed the presence of epithelium derived elastin-producing cells, which was confirmed via in vitro IL-1beta stress induced epithelial-mesenchymal transformation (EMT) morphological and molecular marker changes, which may explain the altered lung elastin deposition and defective septation observed in BPD. CONCLUSIONS: These data support the hypothesis that IL-1beta was initially induced by hyperoxia; alphavbeta6 subsequently interacted with and activated TGF-beta1, acting as an epithelial/mesenchymal signaling molecule that contributed to excessive alveolar elastogenesis, the primary pathological feature of BPD. PMID- 26279427 TI - PRDX6 Protects ARPE-19 Cells from Oxidative Damage via PI3K/AKT Signaling. AB - BACKGROUND/AIMS: Oxidative stress that damages cells of the retinal pigment epithelium (RPE) can cause the development of hereditary retinal disease (HRD). PRDX6, which is a member of the PRDX family, is essential for removing metabolic free radicals from the body. However, the effect of PRDX6 on oxidative stress in HRD remains unknown. In this study, we sought to investigate the role of PRDX6 in oxidative stress-induced HRD in ARPE-19 cells and the molecular mechanism involved. METHODS: ARPE-19 cells were used in the current study. Intracellular ROS levels were determined by flow cytometry. Lipid peroxidation was measured using a commercial MDA assay kit. Cellular variability was determined by MTT assay. Apoptosis was determined using an Annexin V-FITC Apoptosis Detection Kit. mRNA and protein expression levels were detected by real-time PCR and western blot analysis, respectively. RESULTS: We found that H2O2 and blue light could induce significant oxidative stress damage and cell death in ARPE-19 cells. Furthermore, we found that PRDX6 levels significantly decreased after H2O2 treatment. PRDX6 overexpression protected ARPE-19 cells from H2O2- and blue light induced oxidative damage, while PRDX6 knockdown enhanced oxidative damage in these cells. Mechanistically, we found that PRDX6 prevented oxidative damage and promoted ARPE-19 cell survival through the PI3K/AKT signaling pathway. CONCLUSIONS: Collectively, these results suggest that PRDX6 protects ARPE-19 cells from H2O2-induced oxidative stress and apoptosis and that this protection is mediated at least partially through the PI3K/AKT pathway. PMID- 26279428 TI - Lumbar Disc Degeneration is Facilitated by MiR-100-Mediated FGFR3 Suppression. AB - BACKGROUND/AIMS: The pathogenesis of lumbar disc degeneration (LDD) involved activation of matrix metalloproteinase 13 (MMP13) by differential expression of fibroblast growth factor receptor 1 (FGFR1) and FGFR3. Nevertheless, the molecular regulation of FGFR1 and FGFR3 in the lumber disc cells remains elusive. METHODS: We examined the FGFR1 and FGFR3 levels and microRNAs (miRNAs) levels in the resected LDD discs, compared to the traumatized, non-LDD discs. We analyzed the binding of miR-100 to the 3'UTR of FGFR3 mRNA and its effects on FGFR3 translation by bioinformatics analysis and by luciferase-reporter assay, respectively. We modified miR-100 levels in a human nucleus pulposus SV40 cell line (HNPSV), and examined the effects on the expression of FGFR3 and MMP13, by RT-qPCR, Western blot and ELISA. RESULTS: The levels of FGFR1 and miR-100 were significantly higher, while the levels of FGFR3 were significantly lower, in LDD discs, compared to the control non-LDD discs. The levels of FGFR3, but not the levels of FGFR1, inversely correlated with the levels of miR-100. Moreover, miR 100 was found to bind to the 3'UTR of FGFR3 mRNA to prevent its translation. In miR-100-modified HNPSV cells, we found that miR-100 decreased FGFR3 levels, and increased MMP13 levels. CONCLUSION: miR-100 may activate MMP13 through 3'UTR suppressoin of FGFR3 mRNA to facilitate development of LDD. PMID- 26279429 TI - Impact of p38 MAP Kinase Inhibitors on LPS-Induced Release of TNF-alpha in Whole Blood and Primary Cells from Different Species. AB - BACKGROUND/AIMS: Inhibition of p38 mitogen-activated protein kinase (p38 MAPK) is promising for the treatment of inflammatory disorders, however, the efficacy of p38 MAPK inhibitors in clinical trials is limited so far. Since functional sensitivity of p38 MAPK is commonly predicted by preclinical species, we systematically investigated interspecies differences including human tissue. METHODS: Ex vivo test models were established using whole blood and primary cells from different species such as mice, rats, pigs and humans to compare LPS-induced TNF-alpha inhibition of four different p38 MAPK reference inhibitors SB 203580, BIRB-796, Pamapimod, and a Losmapimod analogue as well as a proprietary imidazole based p38 MAPK Inhibitor. RESULTS: All analysed p38 MAPK inhibitors resulted in significant inhibition of LPS-induced TNF-alpha release but with high interspecies differences for dose sensitivity. IC50 values from human whole blood and PBMC showed significant higher sensitivity towards p38 MAPK inhibition compared with data from pig and rat. CONCLUSION: Inhibition of TNF-alpha release by p38 MAPK inhibitors can be reliably identified in well-established laboratory species such as rat or mouse. However, our data indicate that animal models appear to be limited for valid prediction of the inhibitory potential for TNF alpha release in humans. Thus, human tissues should be considered early in the drug development process of p38 MAPK inhibitors. PMID- 26279430 TI - De Novo Mutation in the SCN5A Gene Associated with Brugada Syndrome. AB - BACKGROUND: Brugada syndrome (BrS) is a genetically determined cardiac electrical disorder, characterized by typical electrocardiography (ECG) alterations, and it is an arrhythmogenic syndrome that may lead to sudden cardiac death. The most common genotype found among BrS patients is caused by mutations in the SCN5A gene, which lead to a loss of function of the cardiac sodium (Na(+)) channel (Nav1.5) by different mechanisms. METHODS: The assay of confocal laser microscopy and western blot were used to identify the expression and location of L812Q at the cell surface. Characterization of Nav1.5 L812Q mutant Na(+) channels was text by patch-clamp recordings, and the PHYRE2 server was used to build a model for human Nav1.5 channel. RESULTS: Here, we report that a novel missense SCN5A mutation, L812Q, localized in the DII-S4 transmembrane region of the Nav1.5 channel protein, was identified in an index patient who showed a typical BrS type 1 ECG phenotype. The mutation was absent in the patient's parents and brother. Heterologous expression of the wild-type (WT) and L812Q mutant Nav1.5 channels in human embryonic kidney cells (HEK293 cells) reveals that the mutation results in a reduction of Na(+) current density as well as ~20 mV hyperpolarizing shift of the voltage dependence of inactivation. The voltage dependence of activation and the time course for recovery from inactivation are not affected by the mutation. The hyperpolarizing shift of the voltage dependence of inactivation caused a reduction of the Na(+) window current as well. In addition, western blot and confocal laser microscopy imaging experiments showed that the mutation causes fewer channel to be expressed at the membrane than WT channel. A large proportion of the mutant channels are retained in the cytoplasm, probably in the endoplasmic reticulum. CONCLUSION: The decrease of channel expression, hyperpolarizing shift of voltage dependence of inactivation, and a decline of Na(+) window current caused by L812Q mutation lead to a reduction of Na(+) current during the upstroke and the repolarization phases of cardiac action potential, which contribute to the development of BrS. PMID- 26279431 TI - Low Expression of miR-491 Promotes Esophageal Cancer Cell Invasion by Targeting TPX2. AB - BACKGROUND/AIMS: MicroRNAs (miRNAs) have a key role in carcinogenesis and cancer development, but the role of miRNAs in the progression of esophageal cancer (EC) remains unclear. METHODS: The TE-1 and Eca-109 EC cell lines were used. The expression of miR-491 and candidate gene TPX2 in EC samples (n=99) were detected by RT-PCR. The cells invasive ability was determined by transwell assay. The luciferase reporter assay was used to confirm the regulation mechanism. RESULTS: A decreased expression of miR-491 was detected in the EC clinical samples compared with the corresponding adjacent tumor tissues. Aberrant expression of miR-491 regulated cells invasion and EMT markers. Furthermore, we verified that TPX2 was a target gene of miR-491. CONCLUSIONS: miR-491 may play a critical role in EC. PMID- 26279432 TI - beta-Elemene Reverses Chemoresistance of Breast Cancer Cells by Reducing Resistance Transmission via Exosomes. AB - BACKGROUND: Currently, exosomes that act as mediators of intercellular communication are being researched extensively. Our previous studies confirmed that these exosomes contain microRNAs (miRNAs) that could alter chemo susceptibility, which is partly attributed to the successful intercellular transfer of multidrug resistance (MDR)-specific miRNAs. We also confirmed that beta-elemene could influence MDR-related miRNA expression and regulate the expression of the target genes PTEN and Pgp, which may lead to the reversal of the chemoresistant breast cancer (BCA) cells. We are the first to report these findings, and we propose the following logical hypothesis: beta-elemene can mediate MDR-related miRNA expression in cells, thereby affecting the exosome contents, reducing chemoresistance transmission via exosomes, and reversing the drug resistance of breast cancer cells. METHODS: MTT-cytotoxic, miRNA microarray, real-time quantitative PCR, Dual Luciferase Activity Assay, and Western blot analysis were performed to investigate the impact of beta-elemene on the expression of chemoresistance specific miRNA and PTEN as well as Pgp in chemoresistant BCA exosomes. RESULTS: Drug resistance can be reversed by beta elemene related to exosomes. There were 104 differentially expressed miRNAs in the exosomes of two chemoresistant BCA cells: adriacin (Adr) - resistant MCF-7 cells (MCF-7/Adr) and docetaxel (Doc) - resistant MCF-7 cells (MCF-7/Doc) that underwent treatment. Of these, 31 miRNAs were correlated with the constant changes in the MDR. The expression of miR-34a and miR-452 can lead to changes in the characteristics of two chemoresistant BCA exosomes: MCF-7/Adr exosomes (A/exo) and MCF-7/Doc exosomes (D/exo). The PTEN expression affected by beta elemene was significantly increased, and the Pgp expression affected by beta elemene was significantly decreased in both cells and exosomes. beta-elemene induced a significant increase in the apoptosis rate in both MCF-7/Doc and MCF 7/Adr cells. CONCLUSIONS: Drug resistance can be reversed by beta-elemene, which can alter the expression of some MDR-related miRNAs, including PTEN and Pgp in MCF-7/Adr and MCF-7/Doc in cells. It can therefore affect the exosome contents and induce the reduction of resistance transmission via exosomes. PMID- 26279433 TI - Impact of Janus Kinase 3 on Cellular Ca Release, Store Operated Ca(2+) Entry and Na(+)/Ca(2+) Exchanger Activity in Dendritic Cells. AB - BACKGROUND/AIMS: Janus kinase 3 (JAK3), a tyrosine kinase mainly expressed in hematopoietic cells, participates in the signaling stimulating cell proliferation. The kinase is expressed in dendritic cells (DCs), antigen presenting cells involved in the initiation and regulation of antigen-specific T cell responses. Dendritic cell function is regulated by cytosolic Ca(2+) activity ([Ca(2+)]i). Mediators increasing [Ca(2+)]i in DCs include ATP and the chemokine receptor CXCR4 ligand CXCL12. The present study explored, whether JAK3 participates in the regulation of [Ca(2+)]i in DCs. METHODS: Fura-2 fluorescence was employed to determine [Ca(2+)]i, and whole cell patch clamp to decipher electrogenic transport in immature DCs isolated from bone marrow of JAK3-knockout (jak3(-/-)) or wild-type mice (jak3(+/+)). RESULTS: Without treatment, [Ca(2+)]i was similar in jak3(-/-) and jak3(+/+) DCs. Addition of ATP (100 uM) was followed by transient increase of [Ca(2+)]i reflecting Ca(2+) release from intracellular stores, an effect significantly less pronounced in jak3(-/-) DCs than in jak3(+/+) DCs. CXCL12 administration was followed by a sustained increase of [Ca(2+)]i reflecting receptor operated Ca(2+) entry, an effect significantly less rapid in jak3(-/-) DCs than in jak3(+/+) DCs. In addition, the Ca(2+) release activated Ca(2+) channel (CRAC) current triggered by IP3-induced Ca(2+) store depletion and CXCL12 was significantly higher in DCs from jak3(+/+) mice than in jak3(-/-) mice. Inhibition of sarcoendoplasmatic reticulum Ca(2+)-ATPase (SERCA) by thapsigargin (1 uM) in the absence of extracellular Ca(2+) was followed by a transient increase of [Ca(2+)]i reflecting Ca(2+) release from intracellular stores, and subsequent readdition of extracellular Ca(2+) in the continued presence of thapsigargin was followed by a sustained increase of [Ca(2+)]i reflecting store operated Ca(2+) entry (SOCE). Both, Ca(2+) release from intracellular stores and SOCE were again significantly lower in jak3(-/-) DCs than in jak3(+/+) DCs. Pretreatment of jak3(+/+) DCs with JAK inhibitor WHI-P154 (22 uM, 10 minutes or 24 hours) significantly blunted both thapsigargin induced Ca(2+) release and subsequent SOCE. Abrupt replacement of Na(+) containing (130 mM) and Ca(2+) free (0 mM) extracellular bath by Na(+) free (0 mM) and Ca(2+) containing (2 mM) extracellular bath increased [Ca(2+)]i reflecting Na(+)/Ca(2+) exchanger activity, an effect again significantly less pronounced in jak3(-/-) DCs than in jak3(+/+) DCs. CONCLUSIONS: JAK3 deficiency is followed by down regulation of cytosolic Ca(2+) release, receptor and store operated Ca(2+) entry and Na(+)/Ca(2+) exchanger activity in DCs. PMID- 26279434 TI - Comparative Proteomic Profile of the Human Umbilical Cord Blood Exosomes between Normal and Preeclampsia Pregnancies with High-Resolution Mass Spectrometry. AB - BACKGROUND/AIMS: Exosomes are extracellular vesicles that are involved in several biological processes. The roles of proteins from human umbilical cord blood exosomes in the pathogenesis of preeclampsia remains poorly understood. METHODS: In this study, we used high-resolution LC-MS/MS technologies to construct a comparative proteomic profiling of human umbilical cord blood exosomes between normal and preeclamptic pregnancies. RESULTS: A total of 221 proteins were detected in human umbilical cord blood exosomes, with 14 upregulated and 15 downregulated proteins were definitively identified between preeclamptic and control pregnancies. Further bioinformatics analysis (Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis) indicated that these differentially expressed proteins correlate with enzyme regulator activity, binding, extracellular region, cell part, biological regulation, cellular process and complement and coagulation cascades occurring during pathological changes of preeclampsia. CONCLUSION: Our results show significantly altered expression profiles of proteins in human umbilical cord blood exosomes between normal and preeclampsia pregnancies. These proteins may be involved in the etiology of preeclampsia. PMID- 26279435 TI - Effect of the Total Extract of Averrhoacarambola (Oxalidaceae) Root on the Expression Levels of TLR4 and NF-kappaB in Streptozotocin-Induced Diabetic Mice. AB - BACKGROUND: Averrhoacarambola L., which is a folk medicine used in diabetes mellitus (DM) in ancient China, has been reported to have anti-diabetic efficacy. AIMS: The aim of this study was to evaluate the hypoglycemic effect of the extract of Averrhoacarambola L. root (EACR) on the regulation of the Toll-like receptor 4 (TLR4)-Nuclear-factor kappa B (NF-kappaB) pathway in B) pathway in streptozotocin (STZ)-induced diabetic mice. METHODS: the mice were injected with STZ (120 mg/kg body weight) via a tail vein. After 72 h, the mice with FBG >= 11.1 mmol/L were confirmed as having diabetes. Subsequently, the mice were treated intragastrically with EACR (300, 600, 1200 mg/kg body weight/d) and metformin (320 mg/kg body weight/d) for 14 days. RESULTS: As a result the serum fasting blood glucose (FBG), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) levels were decreased following EACR administration. Immunohistochemical analysis revealed that the pancreatic tissue expression levels of TLR4 and NF-kappaB were downregulated after EACR administration. EACR suppressed pancreatic mRNA expression level of TLR4 and blocked the downstream NF kappaB pathway in the pancreas. According to Western blot analysis EACR suppressed pancreatic TLR4 and NF-kappaB protein expression levels. Histopathological examination of the pancreas showed that STZ-induced pancreas lesions were alleviated by the EACR treatment. CONCLUSION: These findings suggest that the modulation of the IL-6 and TNF-alpha inflammatory cytokines and the suppression of the TLR4-NF-kappaB pathway are most likely involved in the anti hyperglycemic effect of EACR in STZ-induced diabetic mice. PMID- 26279436 TI - An Integrated Approach for the Identification of HNF4alpha-Centered Transcriptional Regulatory Networks During Early Liver Regeneration. AB - BACKGROUND/AIMS: Hepatocyte nuclear factor-4alpha (HNF4alpha), the liver enriched transcription factor (TF), is one of the major regulators of hepatocyte differentiation and proliferation. However, how HNF4alpha participate in liver regeneration after partial hepatectomy (PH) remains largely unknown. In order to identify the HNF4alpha-centered regulatory network, we applied an integrated analytic strategy, in which, TF array, mRNA microarray, bioinformatic analysis and ChIP-on-chip assays were integrated. METHODS/RESULTS: The TF signatures from MOUSE OATFA (TF-array) platform revealed that the activity of HNF4alpha was significantly reduced and 17 other TFs showed increased activity at 4 h post PH. Then the ChIP-on-chip analysis on HNF4alpha were combined with mRNA expression profiling to select the possible HNF4alpha target genes during early liver regeneration, which were then sub-grouped according to their signaling pathways. More specifically, the HNF4alpha target genes with the gene ontology (GO) terms of cytokine-cytokine receptor, Jak-STAT, MAPK, toll-like receptor and insulin signaling pathways were further analyzed with an advanced bioinformatics tool named oPOSSUM to identify TF binding sites occupancy and predict the co regulatory relationship between TFs and targets. Furthermore, we identified that repressed HNF4alpha during the early phase of liver regeneration may contribute cooperatively to the induction of immediate early genes, such as, c-fos, c-jun and stat3. CONCLUSION: our data indicate that HNF4alpha may play an inhibitory role on the induction of specific promitogenic genes and liver regeneration initiation. The integrated approach of mRNA/OATFA/ChIP-DSL/oPOSSUM analysis may help us better characterize the target genes and co-regulatory network of HNF4alpha during the early stage of liver regeneration. PMID- 26279437 TI - Andrographolide Exerts Pro-Osteogenic Effect by Activation of Wnt/beta-Catenin Signaling Pathway in Vitro. AB - BACKGROUND/AIMS: Osteoporosis is a metabolic bone disorders that tortures about millions of people worldwide. Recent studies showed that Andrographolide (AP) is a promising natural compound for the treatment of osteoclast-related bone diseases. However, its potential in treatment of osteoporosis has not been fully explored. METHODS: In this study, the effect of AP on osteoblasts metabolism was investigated via the detection of cell proliferation, cell viability, ALP activity, the expression of osteogenic specific genes including runt-related transcription factor 2 (RUNX2), bone sialoprotein (BSP), osteocalcin (OCN), Bone morphogenic protein-2 (BMP2) and Alkaline phosphatase(ALP) for 3, 5 and 7 days respectively. Further exploration of the association of AP with WNT/beta-catenin signaling pathway was performed by examination of the expression of WNT related genes and proteins. RESULTS: Results showed that AP of 4.46 and 8.92 uM, especially 8.92 uM was beneficial to osteogenic differentiation by upregulating ALP activity and expression of osteogenic related genes (P<0.05). Pathway analyses identify canonical WNT/beta-catenin pathway as an important mediator in AP-induced osteogenesis. CONCLUSION: This study indicates that AP exerts its pro osteogenic potential via activation of the WNT/beta-catenin in osteoblasts and thus may represent a candidate of therapeutic agent for osteoporosis. PMID- 26279438 TI - Interleukin-17 Stimulates STAT3-Mediated Endothelial Cell Activation for Neutrophil Recruitment. AB - BACKGROUND/AIMS: Interleukin-17 (IL-17) is a major pro-inflammatory cytokine that initiates and maintains inflammation. However, the molecular mechanisms as to how IL-17 influences endothelial cells to promote neutrophil recruitment are not fully understood. METHODS: Human endothelial cells (HMECs) were stimulated with IL-17, and investigated for proliferation, migration, and tubule formation activities. Transwell chemotaxis and adhesion assays were performed to assess neutrophil recruitment. Cytokine production was measured by Cytokine Array Chip and ELISA. Western blotting and immunofluorescent analysis were used to detect the phosphorylation and translocation of STAT3. Specific inhibitors, small interfering RNA, and phosphorylation mutants were used to confirm that IL-17 induced STAT3 activation via IL-17RA signaling. RESULTS: Activation of HMECs with IL-17 induced STAT3 phosphorylation and nuclear translocation, which were associated with induction of GRO-alpha, GM-CSF and IL-8, and neutrophil recruitment. Phosphorylation of STAT3 was identified mainly at the tyrosine in position 705 (Y705), and the Y705F mutants attenuated IL-17-mediated STAT3 activation. Moreover, specific inhibitors, FLLL31, or siRNA silencing of STAT3 attenuated HMECs activation, resulting in inhibition of GRO-alpha, GM-CSF, IL-8 production, and neutrophil recruitment. Furthermore, phosphorylation of STAT3 was identified as downstream of IL-17RA signaling. CONCLUSIONS: IL-17 induced STAT3 activation as a necessary step in endothelial cell activation and neutrophil recruitment. PMID- 26279439 TI - MiR-499-5p Contributes to Hepatic Insulin Resistance by Suppressing PTEN. AB - BACKGROUND: Type 2 diabetes afflicts 95% of diabetes patients. Recent data suggest that miRNAs play a key role in insulin production, secretion and function. This study aims to explore the specific role of miR-499-5p in hepatic insulin resistance. METHODS: The miRNA expression levels in the livers of db/db mice were analyzed using miRNA chips and were verified by real-time PCR. miR-499 5p mimics and an inhibitor were transfected into NCTC1469 cells. Then, the PI3K/AKT signaling pathway and glycogen level were determined. The target genes of miR-499-5p were predicted by bioinformatics and then confirmed by dual luciferase reporter assay and Western blot. To establish an insulin resistance (IR) animal model, C57BL/6 mice were fed a high-fat diet (HFD). The level of miR 499-5p in the livers of HFD-fed mice was upregulated through tail vein injection of adenovirus vectors (ad) containing miR-499-5p mimics. The glucose tolerance test (GTT) and insulin tolerance test (ITT) were used to determine glucose tolerance and insulin tolerance, respectively. RESULTS: MicroRNA chips and qPCR showed that miR-499-5p was significantly decreased in the livers of db/db mice. Downregulation of miR-499-5p impaired the insulin signaling pathway and glycogen synthesis, whereas upregulation of miR-499-5p promoted the insulin signaling pathway and glycogen synthesis in NCTC1469 cells. The dual luciferase reporter assay and Western blot demonstrated that PTEN was the target gene of miR-499-5p. Compared with the control group, miR-499-5p was increased 2.1-fold in the livers of HFD-fed mice. By tail vein injection of adenovirus vector containing miR-499 5p mimics, GTT and ITT were improved in HFD-fed mice. CONCLUSION: Downregulation of the miR-499-5p level impaired the PI3K/AKT/GSK signaling pathway and glycogen synthesis by targeting PTEN. PMID- 26279440 TI - The Neuroprotective Effect of Liraglutide is Mediated by Glucagon-Like Peptide 1 Receptor-Mediated Activation of cAMP/PKA/CREB Pathway. AB - BACKGROUND/AIMS: Glucagon-like peptide-1 (GLP-1)-based drugs are being used to achieve better glucose control in patients with type 2 diabetes, and GLP-1 mimetics such as liraglutide have shown therapeutic potential in preventing diabetes-related microvascular and macrovascular complications as well as comorbidities such as neurodegenerative disorders. In the present study, we investigated the effects of liraglutide on primary rat cortical astrocytes treated with advanced glycation end-products (AGEs). METHODS: Gene and protein expression was analyzed by quantitative real time PCR, western blots, and enzyme linked immunosorbent assay. The caspase-3 activity was assessed using a caspase-3 colorimetric assay kit. The ROS production was measured with CM-H2DCFDA staining. The cell viability of rat astrocytes was determined using MTT assay. RESULTS: Liraglutide ameliorated AGEs-induced oxidative stress, inflammatory cytokine secretion, caspase activation, and cell death in astrocytes, and reversed the AGEs mediated reduction in intracellular cyclic AMP (cAMP) levels, protein kinase A (PKA) activity, and the phosphorylation of the cAMP response element-binding (CREB) protein. The protective effects of liraglutide against AGEs-mediated toxicity were abolished by GLP-1 receptor (GLP-1R) knockdown or pretreatment of cells with the adenylyl cyclase inhibitor SQ22536 or the PKA inhibitor Rp-cAMP. CONCLUSIONS: Liraglutide exerts its neuroprotective effects via the GLP-1R mediated activation of the cAMP/PKA/CREB pathway. The results of the present study support the therapeutic potential of liraglutide for the treatment of neurodegenerative disorders. PMID- 26279442 TI - Circulating Hepatocellular Carcinoma Cells are Characterized by CXCR4 and MMP26. AB - BACKGROUND/AIMS: Primary hepatocellular carcinoma (HCC) is highly invasive, and often results in an early distal metastasis resulting in poor prognosis and therapeutic outcome. Cancer cells disseminating from the tumor and entering circulation are termed circulating tumor cells (CTCs). Although substantial progress has been made to identify those CTCs in HCC, no good marker (cocktail) has so far been identified. METHODS: Since only tumorigenic CTCs form metastatic tumor in distal organs, we thus compared the HCC cells that form tumor spheres in culture to those that do not. We transduced HCC cells with a RFP reporter under MMP26 promoter and purified MMP26+CXCR4+ HCC cells. We examined tumor sphere formation in culture, presence of tumor cells in the circulation as well as capability of developing metastatic tumor after transplantation of MMP26+CXCR4+ HCC cells into nude mice, compared to other populations in HCC. RESULTS: Sphere forming HCC cells expressed high levels of MMP26 and CXCR4. MMP26+CXCR4+ HCC cells formed significantly more tumor spheres in culture, compared to MMP26-CXCR4 , MMP26-CXCR4+ or MMP26+CXCR4- HCC cells. Moreover, tumor cells were more frequently detected in the circulation when MMP26+CXCR4+ HCC cells were subcutaneously transplanted. Further, subcutaneous transplantation of MMP26+CXCR4+ HCC cells, but not transplantation of MMP26-CXCR4-, MMP26-CXCR4+ or MMP26+CXCR4-HCC cells significantly developed distal metastatic tumors. CONCLUSION: MMP26+CXCR4+ cells may be CTCs in HCC. Selective elimination of MMP26+CXCR4+ cells may substantially reduce HCC metastasis after primary tumor resection. PMID- 26279441 TI - Virus-Induced Type I Interferon Deteriorates Control of Systemic Pseudomonas Aeruginosa Infection. AB - BACKGROUND: Type I interferon (IFN-I) predisposes to bacterial superinfections, an important problem during viral infection or treatment with interferon-alpha (IFN-alpha). IFN-I-induced neutropenia is one reason for the impaired bacterial control; however there is evidence that more frequent bacterial infections during IFN-alpha-treatment occur independently of neutropenia. METHODS: We analyzed in a mouse model, whether Pseudomonas aeruginosa control is influenced by co-infection with the lymphocytic choriomeningitis virus (LCMV). Bacterial titers, numbers of neutrophils and the gene-expression of liver-lysozyme-2 were determined during a 24 hours systemic infection with P. aeruginosa in wild-type and Ifnar(-/-) mice under the influence of LCMV or poly(I:C). RESULTS: Virus-induced IFN-I impaired the control of Pseudomonas aeruginosa. This was associated with neutropenia and loss of lysozyme-2-expression in the liver, which had captured P. aeruginosa. A lower release of IFN-I by poly(I:C)-injection also impaired the bacterial control in the liver and reduced the expression of liver-lysozyme-2. Low concentration of IFN-I after infection with a virulent strain of P. aeruginosa alone impaired the bacterial control and reduced lysozyme-2-expression in the liver as well. CONCLUSION: We found that during systemic infection with P. aeruginosa Kupffer cells quickly controlled the bacteria in cooperation with neutrophils. Upon LCMV infection this cooperation was disturbed. PMID- 26279443 TI - Lipopolysaccharide Induces Autophagic Cell Death through the PERK-Dependent Branch of the Unfolded Protein Response in Human Alveolar Epithelial A549 Cells. AB - BACKGROUND: Alveolar epithelial cell death plays a critical role in the pathogenesis of lipopolysaccharide (LPS)-induced acute lung injury. Increased autophagy has a dual effect on cell survival. However, it is not known whether autophagy promotes death or survival in human alveolar epithelial cells exposed to LPS. METHODS: Genetic and pharmacological approaches were used to evaluate the effect of autophagy on A549 cell viability upon LPS exposure. The endoplasmic reticulum (ER) stress and unfolded protein response (UPR) pathways were examined with immunoblotting studies to further explore underlying mechanisms. RESULTS: Treatment with LPS (50 ug/ml) led to autophagy activation and decreased cell viability in A549 cells. Blocking autophagy via short interfering RNA or inhibitor significantly decreased, whereas rapamycin increased, the LPS-induced effect on viability. ER stress was activated in LPS-stimulated A549 cells, and ER stress inhibitor reduced LPS-induced autophagy. LPS activated only the PERK pathway and had rarely effect on the ATF6 and IRE1 branches of the UPR in A549 cells. Moreover, the knockdown of PERK and ATF4 attenuated LPS-induced autophagy and promoted cell survival. CONCLUSION: In human alveolar epithelial A549 cells, LPS induces autophagic cell death that depends on the activation of the PERK branch of the UPR upon ER stress. PMID- 26279444 TI - The Roles of p38 MAPK and ERK1/2 in Coplanar Polychlorinated Biphenyls-Induced Apoptosis of Human Extravillous Cytotrophoblast-Derived Transformed Cells. AB - BACKGROUND/AIMS: The purpose of this study was to investigate the relationships among exposure to coplanar polychlorinated biphenyls (Co-PCBs), the expression of gC1qR and the underlying intracellular apoptotic signaling pathways of human extravillous cytotrophoblast (EVCT)-derived transformed cells (HTR-8/SVneo and HPT-8). METHODS: Apoptosis in HTR-8/SVneo and HPT-8 cells was assessed using flow cytometric analysis. gClqR expression was examined in the HTR-8/SVneo and HPT-8 cells using real-time qPCR and western blot analyses. The phosphorylations of p38 mitogen-activated protein kinase (p38 MAPK) (Thr180/Tyr182) and extracellular signal-regulated kinase (ERK) 1/2 (Thr202/Thr204) were detected using western blot analyses. RESULTS: The HTR-8/SVneo and HPT-8 cells treated with Co-PCBs exhibited significantly increased gClqR expression, p38 MAPK/ERK activation and an up-regulation of cellular apoptosis. These effects were abrogated by the application of gC1qR small interfering RNA (siRNA). Furthermore, apoptosis in HTR 8/SVneo and HPT-8 cells was observed upon treatment with Co-PCBs, and these effects were reversed by the p38 MAPK pathway inhibitor SB203580 or the ERK1/2 pathway inhibitor PD098059. CONCLUSION: These data support a mechanism wherein gC1qR plays a crucial p38 MAPK/ERK signaling pathway-dependent role in Co-PCBs induced apoptosis of human EVCT-derived transformed cells. PMID- 26279445 TI - Eruberin A, a Natural Flavanol Glycoside, Exerts Anti-Fibrotic Action on Pancreatic Stellate Cells. AB - BACKGROUND: Eruberin A (2, 3-dehydroflavonoid), a flavanol glycoside isolated from Pronephrium penangianum, has been used as a blood-nourishing folk medicine for centuries; however, it indeed possesses a variety of other health-promoting benefits including anti-fibrotic bioactivity. Activation of pancreatic stellate cells (PSCs) is the key initiating step in pancreatic fibrosis, which is a characteristic feature associated with chronic pancreatitis and pancreatic adenocarcinoma. METHODS: The anti-fibrotic effect of eruberin A and the underlying mechanisms of its anti-fibrotic action in LTC-14 cells, which retained essential characteristics and morphological features of primary PSCs, were examined by means of real-time polymerase chain reactions, Western blotting and immunostaining. RESULTS: The application of eruberin A (20 MUg/ml) effectively inhibited the expression levels of fibrotic mediators namely alpha-smooth muscle actin, fibronectin and type I-collagen, so as the sonic hedgehog signaling pathway components post transforming growth factor-beta (5 ng/ml) stimulation. Eruberin A treatment also led to a notable decrease in the activation of nuclear factor-kappaB (NF-kappaB) and the phosphorylation of phosphoinositide 3-kinase (PI3K)/serine-threonine kinase (AKT). CONCLUSION: Our results demonstrated that eruberin A significantly suppressed the expression levels of fibrotic mediators in PSCs, and we suggest that its anti-fibrotic mechanism was associated with an attenuation of the PI3K/AKT/NF-kappaB signaling pathway. PMID- 26279446 TI - Lgr5-Positive Cells are Cancer-Stem-Cell-Like Cells in Gastric Cancer. AB - BACKGROUND/AIMS: Effective treatment of gastric cancer (GC) requires better understanding of the molecular regulation of its carcinogenesis. Identification of cancer stem cells (CSCs) in GC appears to be a critical question. METHODS: We analyzed Lgr5 expression in GC specimen. We used an adeno-associated virus (AAV) that carries diphtheria toxin fragment A (DTA) under the control of Lgr5 promoter (AAV-pLgr5-DTA) to transduce human GC cells. The growth of GC cells with/without depletion of Lgr5-positive cells was studied in vitro in an MTT assay, and in vivo by analyzing bioluminescence levels. RESULTS: A portion of GC cells in the resected specimen expressed Lgr5. GC cells that formed tumor spheres expressed high Lgr5. Selective depletion of Lgr5-positive GC cells resulted in significant growth inhibition of GC cells in vitro and in vivo. CONCLUSION: Lgr5-positive cells may be CSCs-like cells in GC and may play a pivotal role in the tumorigenesis of GC. Treating Lgr5-positive GC cells may substantially improve the therapeutic outcome. PMID- 26279447 TI - Lactoferrin Inhibits IL-1beta-Induced Chondrocyte Apoptosis Through AKT1-Induced CREB1 Activation. AB - BACKGROUND/AIMS: Chondrocyte apoptosis is largely responsible for cartilage degeneration in osteoarthritis (OA). Interleukin-1 beta (IL-1beta) is widely used as a chondrocyte apoptosis-inducing agent, while lactoferrin (LF) is an anabolic reagent which has the potential to inhibit chondrocyte apoptosis. We assessed the effects of LF on cartilage degeneration in IL-1beta-induced chondrocytes and in a rat model of OA, and explored the potential molecular mechanisms involved. METHODS: Human articular chondrocytes (HACs) were treated with IL-1beta alone or in combination with LF. MTT and flow cytometric assays were used to detect changes after treatment with LF. Western blotting was used to examine the relevant molecules regulating apoptosis. RESULTS: We found that IL-1beta reduced the viability of HACs, whereas 200 MUg/mL of LF significantly counteracted the inhibitory effect of IL-1beta. LF significantly inhibited IL-1beta-induced HAC apoptosis. The protein expression of the apoptotic markers Caspase-3 and PARP was also significantly reduced in the LF treatment group when analyzed by western blotting. Furthermore, we found that LF triggered CREB1 phosphorylation in IL 1beta-induced HAC apoptosis through AKT1 signaling. In addition, LF promoted the repair of articular cartilage damage in a rat OA model with elevated p-CREB levels. CONCLUSIONS: These studies suggest that LF has an anti-apoptotic effect on IL-1beta-induced chondrocytes, and thus may be a promising novel therapeutic agent for OA. PMID- 26279448 TI - Effect of Salusin-beta on Peroxisome Proliferator-Activated Receptor Gamma Gene Expression in Vascular Smooth Muscle Cells and its Possible Mechanism. AB - BACKGROUND/AIMS: salusin-beta is considered to be a potential pro-atherosclerotic factor. Regulation and function of vascular smooth muscle cells (VSMCs) are important in the progression of atherosclerosis. Peroxisome proliferator activated receptor gamma (PPARgamma) exerts a vascular protective role beyond its metabolic effects. Salusin-beta has direct effects on VSMCs. The aim of the present study was to assess the effect of salusin-beta on PPARgamma gene expression in primary cultured rat VSMCs. METHODS: Western blotting analysis, real-time PCR and transient transfection approach were used to determine expression of target proteins. Specific protein knockdown was performed with siRNA transfection. Cell proliferation was determined by 5-bromo-2'-deoxyuridine incorporation. The levels of inflammation indicators interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were determined using enzyme-linked immunosorbent assay. RESULTS: Salusin-beta negatively regulated PPARgamma gene expression at protein, mRNA and gene promoter level in VSMCs. The inhibitory effect of salusin-beta on PPARgamma gene expression contributed to salusin-beta induced VSMCs proliferation and inflammation in vitro. IkappaBalpha-NF-kappaB activation, but not NF-kappaB p50 or p65, mediated the salusin-beta-induced inhibition of PPARgamma gene expression. Salusin-beta induced nuclear translocation of histone deacetylase 3 (HDAC3). HDAC3 siRNA prevented salusin beta-induced PPARgamma reduction. Nuclear translocation of HDAC3 in response to salusin-beta was significantly reversed by an IkappaBalpha inhibitor BAY 11-7085. Furthermore, IkappaBalpha-HDAC3 complex was present in the cytosol of VSMCs but interrupted after salusin-beta treatment. CONCLUSION: IkappaBalpha-HDAC3 pathway may contribute to salusin-beta-induced inhibition of PPARgamma gene expression in VSMCs. PMID- 26279449 TI - Osthole Inhibits Proliferation and Induces Catabolism in Rat Chondrocytes and Cartilage Tissue. AB - BACKGROUND/AIMS: Cartilage destruction is thought to be the major mediator of osteoarthritis. Recent studies suggest that inhibition of subchrondral bone loss by anti-osteoporosis (OP) drug can protect cartilige erosion. Osthole, as a promising agent for treating osteoporosis, may show potential in treating osteoarthritis. The purpose of this study was to investigate whether Osthole affects the proliferation and catabolism of rat chondrocytes, and the degeneration of cartilage explants. METHODS: Rat chondrocytes were treated with Osthole (0 MUM, 6.25 MUM, 12.5 MUM, and 25 MUM) with or without IL1-beta (10ng/ml) for 24 hours. The expression levels of type II collagen and MMP13 were detected by western Blot. Marker genes for chondrocytes (A-can and Sox9), matrix metalloproteinases (MMPs), aggrecanases (ADAMTS5) and genes implicated in extracellular matrix catabolism were evaluated by qPCR. Cell proliferation was assessed by measuring proliferating cell nuclear antigen (PCNA) expression and fluorescence activated cell sorter. Wnt7b/beta-catenin signaling was also investigated. Cartilage explants from two-week old SD rats were cultured with IL 1beta, Osthole and Osthole plus IL-1beta for four days and glycosaminoglycan (GAG) synthesis was assessed with toluidine blue staining and Safranine O/Fast Green FCF staining, collagen type II expression was detected by immunofuorescence. RESULTS: Osthole reduced expression of chondrocyte markers and increased expression of MMP13, ADAMTS5 and MMP9 in a dose-dependent manner. Catabolic gene expression levels were further improved by Osthole plus IL-1beta. Osthole inhibited chondrocyte proliferation. GAG synthesis and type II collagen were decreased in both the IL-1beta groups and the Osthole groups, and significantly reduced by Osthole plus IL-1beta. CONCLUSIONS: Our data suggested that Osthole increases the catabolism of rat chondrocytes and cartilage explants, this effect might be mediated through inhibiting Wnt7b/beta-catenin pathway. PMID- 26279450 TI - N1-Guanyl-1,7-Diaminoheptane Sensitizes Estrogen Receptor Negative Breast Cancer Cells to Doxorubicin by Preventing Epithelial-Mesenchymal Transition through Inhibition of Eukaryotic Translation Initiation Factor 5A2 Activation. AB - BACKGROUND: Approximately 30% of breast cancer does not express the estrogen receptor (ER), which is necessary for endocrine-based therapy approaches. Many studies demonstrated that eukaryotic translation initiation factor 5A2 (eIF5A2) serves as a proliferation-related oncogene in tumorigenic processes. METHODS: The present study used cell viability assays, EdU incorporation assays, western blot, and immunofluorescence to explore whether N1-guanyl-1,7-diaminoheptane (GC7), which inhibits eIF5A2 activation, exerts synergistic cytotoxicity with doxorubicin in breast cancer. RESULTS: We found that GC7 enhanced doxorubicin cytotoxicity in ER-negative HCC1937 cells but had little effect in ER-positive MCF-7 and Bcap-37 cells. Administration of GC7 reversed the doxorubicin-induced epithelial-mesenchymal transition (EMT) in ER-negative breast cancer cells. Knockdown of eIF5A2 by siRNA inhibited the doxorubicin-induced EMT in ER-negative HCC1937 cells. CONCLUSION: These data demonstrated that GC7 combination therapy may enhance the therapeutic efficacy of doxorubicin in estrogen negative breast cancer cells by preventing EMT through inhibition of eIF5A2 activation. PMID- 26279451 TI - Carbon isotope ratios of human tooth enamel record the evidence of terrestrial resource consumption during the Jomon period, Japan. AB - OBJECTIVE: Archaeological remains strongly suggest that the Holocene Japanese hunter-gatherers, the Jomon people, utilized terrestrial plants as their primary food source. However, carbon and nitrogen isotope analysis of bone collagen indicates that they primarily exploited marine resources. We hypothesize that this inconsistency stems from the route of protein synthesis and the different proportions of protein-derived carbon in tooth enamel versus bone collagen. Carbon isotope ratios from bone collagen reflect that of dietary protein and may provide a biased signal of diet, whereas isotope ratios from tooth enamel reflect the integrated diet from all macronutrients (carbohydrates, lipids, and proteins). METHODS: In order to evaluate the differences in inferred diet between the archaeological evidence and bone collagen isotope data, this study investigated carbon isotopes in Jomon tooth enamel from four coastal sites of the Middle to Late-Final Jomon period (5,000-2,300 years BP). RESULTS: Carbon isotope ratios of human teeth are as depleted as coeval terrestrial mammals, suggesting that C3 plants and terrestrial mammals were major dietary resources for the Jomon people. Dietary dependence on marine resources calculated from enamel was significantly lower than that calculated from bone collagen. The discrepancy in isotopic ratios between enamel and collagen and the nitrogen isotope ratio in collagen shows a negative correlation on individual and population levels, suggesting diets with variable proportions of terrestrial and marine resources. CONCLUSION: This study highlights the usefulness of coupling tooth enamel and bone collagen in carbon isotopic studies to reconstruct prehistoric human diet. Am J Phys Anthropol 158:300-311, 2015. (c) 2015 Wiley Periodicals, Inc. PMID- 26279452 TI - Variation in the TAS1R2 Gene, Sweet Taste Perception and Intake of Sugars. AB - BACKGROUND/AIMS: To determine whether variation in the TAS1R2 gene affects sucrose taste perception and sugar intake. METHODS: Participants were men (n = 238) and women (n = 458) aged 20-29 years. A subset (n = 95) with body mass index (BMI) data available completed a sensory analysis study. A food frequency questionnaire assessed dietary intake, and eight polymorphisms were genotyped (rs12033832, rs12137730, rs35874116, rs3935570, rs4920564, rs4920566, rs7513755 and rs9701796). Sucrose taste thresholds were determined by staircase procedure (solutions: 9 * 10-6 to 0.5 mol/l). Suprathreshold sensitivity to 0.01-1.0 mol/l sucrose solutions was assessed using general Labeled Magnitude Scales. RESULTS: A significant genotype-BMI interaction was observed for rs12033832 (G>A) for suprathreshold sensitivity (p = 0.01) and sugar intake (p = 0.003). Among participants with a BMI >=25, G allele carriers had lower sensitivity ratings (mean incremental area under the taste sensitivity curve +/- SE; GG/GA 54.4 +/- 4.1 vs. AA 178.5 +/- 66.6; p = 0.006), higher thresholds (GG/GA 9.3 +/- 1.1 vs. AA 4.4 +/- 4.3 mmol/l; p = 0.004) and consumed more sugars (GG/GA 130 +/- 4 vs. AA 94 +/- 13 g/day; p = 0.009). G allele carriers with a BMI <25 had lower thresholds (GG/GA 8.6 +/- 0.5 vs. AA 16.7 +/- 5.7 mmol/l; p = 0.02) and consumed less sugars (GG/GA 122 +/- 2 vs. AA 145 +/- 8 g/day; p = 0.004). CONCLUSION: The rs12033832 single nucleotide polymorphism in TAS1R2 is associated with sucrose taste and sugar intake, but the effect differs depending on BMI. PMID- 26279453 TI - Distribution of radioactive cesium and its seasonal variations in cattle living in the "difficult-to-return zone" of the Fukushima nuclear accident. AB - The amount of radioactive cesium in various tissues of cattle which lived in the highly contaminated area designated as the "difficult-to-return zone", was measured in May and December of 2014. The average concentration of radioactive cesium in the skeletal muscles ranged from 3900 to 5500 Bq/kg, and there was no significant difference between May and December. The sirloin (in December), tenderloin and top round (in May and December) showed significantly higher concentrations of cesium than the neck muscle, which is generally used for the radioactivity inspection. The Longus colli muscle, which is also used for the inspection in some institutions, showed the same radioactivity as the neck muscle. Study results indicated that relative cesium concentrations in internal organs were higher in May compared to December. There were high correlations of cesium concentration between the blood and other tissues. However, regression coefficients between the blood and muscles were significantly higher in December than those in May. When radioactivity in the neck or Longus colli muscles between 50 to 100 Bq/kg is detected, the slaughtered cattle should be re-inspected using another muscle, such as top round or sirloin, to prevent marketing of meat that violates the criteria of the Food Sanitation Act. PMID- 26279454 TI - Schizophrenia-like symptoms in narcolepsy type 1: shared and distinctive clinical characteristics. AB - BACKGROUND/AIMS: The occurrence of psychotic symptoms in narcolepsy type 1 (NT1) has been reported as responsible for delayed diagnosis due to the misdiagnosis of schizophrenia. This study aimed to identify shared and distinctive clinical characteristics between NT1 and schizophrenia, with the focus on psychotic symptoms. METHODS: A total of 28 NT1 and 21 schizophrenia patients were included. Hallucination characteristics and PANSS (Positive and Negative Syndrome Scale), HRSD (Hamilton Rating Scale for Depression), DES (Dissociative Experiences Scale), and STAI (State-Trait Anxiety Inventory) scores were collected. Symptom overlap was investigated by chi(2), Fisher's or t tests and multiple logistic regression models. RESULTS: Hallucinations and illusions frequently occurred in both diseases. Unimodal hallucinations were more common in schizophrenia (p = 6.30e-07) and multimodal hallucinations in NT1, but no clear difference was identified in their sensory modality. Hypnagogic/hypnopompic hallucinations were typical of NT1 (p = 5.22e-07), and 25% of NT1 patients exhibited some degree of insight deficit. Hypnagogic/hypnopompic hallucinations, unimodal hallucinations and PANSS score were the most distinctive clinical characteristics. Clinical overlap was found in the dissociative and anxiety domains, while higher depressive scores were observed in schizophrenia. CONCLUSION: The overlap between NT1 and schizophrenia should be further investigated under a clinical and pathogenetic point of view to improve diagnostic and therapeutic approaches. PMID- 26279455 TI - Efficacy and safety of diagnostic thoracoscopy in undiagnosed pleural effusions. AB - BACKGROUND: The differential diagnosis of pleural effusions can present a considerable challenge, and the etiology of pleural effusions varies depending on the population studied. OBJECTIVE: This study aimed to assess the efficacy and safety of medical thoracoscopy in the diagnosis of patients with undiagnosed pleural effusions in a Chinese population. METHODS: Between July 2005 and June 2014, medical thoracoscopy (MT) using the semirigid instrument was performed in 833 patients with pleural effusions of unknown etiology in our Institute, where diagnostic thoracocentesis or/and blind pleural biopsy had failed to yield an answer. Demographic, radiographic, procedural, and histological data were recorded and analyzed. RESULTS: During this 9-year study, satisfactory pleural biopsy samples were obtained in 833 patients, and MT revealed malignant pleural effusion in 342 (41.1%) patients, benign pleural effusion in 429 (51.5%) patients, and 62 (7.4%) patients could not get definite diagnoses. The overall diagnostic efficiency of MT was 92.6% (771/833). After MT, the only severe complication was empyema, seen in 3 patients (0.4%). The most common minor complication was transient chest pain (44.1%) from the indwelling chest tube. CONCLUSIONS: MT is an effective and safe procedure for diagnosing pleural effusions of undetermined causes. In areas with high tuberculosis prevalence, MT should be particularly helpful in the differential diagnosis of tuberculous pleural effusion. PMID- 26279456 TI - Photovoltaic Effect and Evidence of Carrier Multiplication in Graphene Vertical Homojunctions with Asymmetrical Metal Contacts. AB - Graphene exhibits exciting potentials for high-speed wideband photodetection and high quantum efficiency solar energy harvest because of its broad spectral absorption, fast photoelectric response, and potential carrier multiplication. Although photocurrent can be generated near a metal-graphene interface in lateral devices, the photoactive area is usually limited to a tiny one-dimensional line like interface region. Here, we report photoelectric devices based on vertical graphene two-dimensional homojunction, which is fabricated via vertically stacking four graphene monolayers with asymmetric metal contacts. The devices show excellent photovoltaic output with excitation wavelength ranging from visible light to mid-infrared. The wavelength dependence of the internal quantum efficiency gives direct evidence of the carrier multiplication effect in graphene. The simple fabrication process, easy scale-up, large photoresponsive active area, and broadband response of the vertical graphene device are very promising for practical applications in optoelectronics and photovoltaics. PMID- 26279457 TI - Impact of epidermal growth factor receptor and transforming growth factor-alpha on hepatitis C virus-induced hepatocarcinogenesis. AB - Epidermal growth factor receptor system plays a central hepato-protective and pro regenerative role in liver. Transforming growth factor-alpha (TGF-alpha) is an important autocrine growth regulator of hepatocytes that plays a role in development of hepatocellular carcinoma (HCC) among patients with chronic hepatitis C (CHC). This study was done on 40 core liver biopsies from patients with CHC, 20 liver specimens from HCC cases on top of CHC as well as five normal controls. All were immunohistochemically stained with epidermal growth factor receptor (EGFR) and TGF-alpha antibodies. Some selected HCC cases were submitted for FISH technique to detect EGFR gene alteration. By immunohistochemistry EGFR and TGF-alpha were overexpressed in HCC and cirrhotic cases compared to CHC cases without cirrhosis. Also, their expression was stronger in CHC cases with higher grades of activity and stages of fibrosis compared to lower ones. FISH positive results for EGFR were detected in 33.3% of the examined HCC cases. EGFR and TGF alpha can be used as predictive markers for activity, fibrosis, and carcinogenesis in CHC patients. Overexpression of EGFR in HCC patients can be promising in selecting those who can get benefit from anti-EGFR target therapy. PMID- 26279458 TI - The impact of persistence with bisphosphonates on health resource utilization and fracture risk in the UK: a study of patient records from the UK Clinical Practice Research Datalink. AB - RATIONALE, AIMS AND OBJECTIVES: Clinical trial data suggest that patients who have received bisphosphonates continue to benefit from them after discontinuation. However, data from real-world clinical practice are inconclusive. We assessed the impact of persistence and discontinuation on health resource utilization (HRU) and fracture rate in women who were prescribed oral bisphosphonates. METHOD: The study used data from the UK Clinical Practice Research Datalink. Women aged 50 years or older with a first prescription of oral bisphosphonate therapy between January 2000 and December 2007 were included. Multivariate modelling compared rate ratios for fracture and HRU between patients who had discontinued medication (shorter persistence group) and patients who took their medication for longer (longer persistence group). The interactions of elapsed time (measured as 6-month intervals) with HRU and with fracture rate for all patients within paired groups were also assessed. RESULTS: Overall, 36 320 patients were included. Pairwise comparisons showed that HRU and fracture rates were lower in longer persistence groups than in shorter persistence groups. Analysis by 6-month interval showed that, across all patients in persistence group pairs, HRU significantly increased for each additional 6 months elapsed; trends towards increased risk of fracture were also seen. CONCLUSION: In contrast to results from clinical trials, in this patient population the protective effect of oral bisphosphonates after discontinuation was not sufficient to reduce HRU and fracture rates to the levels that would be seen if patients had continued on therapy. Reducing the rate of treatment discontinuation may decrease the burden that osteoporosis places on both patients and health care systems. PMID- 26279459 TI - Temporal Trends and Outcomes Associated with Major Bleeding in Acute Coronary Syndromes: A Decade-Long Perspective from the Acute Coronary Syndrome Israeli Surveys 2000-2010. AB - OBJECTIVES: The implementation of an early invasive approach and the increased use of potent anti-thrombotic drugs have resulted in higher rates of major bleeding events (MBE) in patients with acute coronary syndrome (ACS). There are limited data on the temporal trends for the rates of MBE over the last decade and associated outcomes. METHODS: Rates, characteristics, risk factors and clinical outcomes associated with MBE were assessed among 11,538 patients enrolled in the biennial Acute Coronary Syndrome Israeli Surveys (ACSIS) 2000-2010. RESULTS: A total of 143 patients (1.2%) experienced MBE during the index hospitalization for ACS. There was a significant increase in the risk of MBE in the late (2006-2010) versus the early (2000-2004) surveys (0.9 and 1.6% respectively, adjusted OR 1.86, p < 0.001). In the multivariate analysis, factors independently associated with a significant increase in the risk of MBE included undergoing primary percutaneous coronary intervention (OR 2.21, p < 0.005), experiencing renal failure (OR 4.19, p < 0.001) and systolic blood pressure level at admission (OR 1.12, per 10- mm Hg decrement, p = 0.011). Patients who experienced MBE had a >3.5-fold increased risk for 1-year mortality (adjusted HR = 3.52, p < 0.001). Interestingly, the mortality risk associated with MBE was evident only among those who experienced non-access-site bleeding (HR = 1.9; p = 0.001). CONCLUSIONS: In the past decade, there has been a significant increase in the rate of MBE. However, we found that only major bleeding that was not related to the vascular access site affected subsequent mortality. PMID- 26279460 TI - De novo congenital malignant melanoma: whats new in diagnosis and treatment? PMID- 26279461 TI - Pap smear screening, pap smear abnormalities and psychosocial risk factors among women in a residential alcohol and drug rehabilitation facility. AB - AIM: To compare rates of late- screening, abnormal Pap smears and prevalence of psychosocial factors for cervical cancer between women in the community and women attending a residential drug and alcohol facility. BACKGROUND: Women with drug and alcohol addiction experience higher rates of abnormal Pap smears, late- or under- screening and psychosocial risk factors including domestic violence and sexual assault. DESIGN: A descriptive cross-sectional study of women attending publically funded women's health clinics in the community or in a live-in residential drug and alcohol rehabilitation facility. METHODS: The study was approved in May 2012. Data were collected between October 2012-December 2013 using standardized women's health questionnaires, domestic violence screening tools and Pap smear tests. RESULTS: Women attending the rehabilitation facility had higher rates of abnormal Pap smears (16.7% vs. 1.6%) and self-reported history of abnormal Pap smears (44.4% vs. 20.6%). They also reported higher rates of smoking (72.2% vs. 29.2%), experience of sexual assault (44.1% vs. 16.9%), experience of domestic violence (65.7% vs. 10.9%) and other psychosocial risk factors, than women living in the general community. Unexpectedly, women in the rehabilitation facility reported similar levels of late screening as women in the community (52.8% vs. 55.4%). CONCLUSION: Women with drug and alcohol addiction have significantly higher incidence of risk factors for cervical cancer and abnormal Pap smears. Provision of opportunistic cervical cancer screening during residential treatment appears to reduce incidence of late-screening. Roles of Women's Health Nurses in providing services to vulnerable women should be explored further. PMID- 26279462 TI - Von Hippel-Lindau Syndrome. AB - Von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome characterized by the development of multiple vascular tumours. The syndrome is caused by inactivation of the VHL protein (pVHL) and increased production of VEGF, PDGF, and TGF-alpha. The course of VHL syndrome is associated with the development of multiple vascular tumours. Most frequently, these include retinal and central nervous system haemangioblastomas, clear cell renal cell carcinoma, phaeochromocytomas, pancreatic islet tumours, endolymphatic sac tumours, and additionally, renal and pancreatic cystadenomas and epididymal cystadenomas in men. VHL syndrome is a highly complex disease; hence, the diagnosis is often difficult. The diagnosis of any of the characteristic tumours, particularly in children, is an implicit indication for the necessity of diagnosis and genetic tests in the patient and family members and for intensive supervision of carriers of the mutated gene, thereby improving early diagnosis and successful treatment of the malignancies. PMID- 26279463 TI - Prenatal Exposure to Maternal Obesity Alters Anxiety and Stress Coping Behaviors in Aged Mice. AB - BACKGROUND: There is growing evidence that maternal obesity and prenatal exposure to a high-fat diet program fetal development to regulate the physiology and behavior of the offspring in adulthood. Yet the extent to which the maternal dietary environment contributes to adult disease vulnerability remains unclear. In the current study we tested whether prenatal exposure to maternal obesity increases the offspring's vulnerability to stress-related psychiatric disorders. METHODS: We used a mouse model of maternal diet-induced obesity to investigate whether maternal obesity affects the response to adult chronic stress exposure in young adult (3-month-old) and aged adult (12-month-old) offspring. RESULTS: Long lasting, delayed impairments to anxiety-like behaviors and stress coping strategies resulted on account of prenatal exposure to maternal obesity. Although maternal obesity did not change the offspring's behavioral response to chronic stress per se, we demonstrate that the behavioral outcomes induced by prenatal exposure to maternal obesity parallel the deleterious effects of adult chronic stress exposure in aged male mice. We found that the glucocorticoid receptor (GR, Nr3c1) is upregulated in various hypothalamic nuclei on account of maternal obesity. In addition, gene expression of a known regulator of the GR, FKBP51, is increased specifically within the paraventricular nucleus. CONCLUSIONS: These findings indicate that maternal obesity parallels the deleterious effects of adult chronic stress exposure, and furthermore identifies GR/FKBP51 signaling as a novel candidate pathway regulated by maternal obesity. PMID- 26279464 TI - Association of Controlled and Uncontrolled Hypertension With Workplace Productivity. AB - The authors estimated the lost productive time (LPT) due to absenteeism and presenteeism among employees at the Group Health Cooperative with controlled and uncontrolled hypertension compared with normotensive patients. The patients responded to a survey inquiring about health behaviors with links to their medical record to identify diagnoses, blood pressure measurement, and prescription drug dispenses. Individuals with controlled hypertension were more likely to report any LPT relative to individuals with uncontrolled hypertension (40.6% vs 32.6%, P<.05). There were no significant differences in the average hours of LPT due to presenteeism among individuals regardless of their hypertension status but individuals with hypertension were more likely to report hours of LPT due to absenteeism compared with normotensive individuals (1.04 vs 0.59 hours; P=.001). Individuals with uncontrolled hypertension were more likely to report LPT due to absenteeism compared with individuals with controlled hypertension (1.35 vs 0.72 hours; P=.001). There were no significant differences between individuals with hypertension whose blood pressure was controlled and normotensive individuals with respect to the likelihood of reporting any LPT or in the amounts of absenteeism and presenteeism. PMID- 26279465 TI - Assessment of the Combined Treatment with Umbelliferone and Four Classical Antiepileptic Drugs Against Maximal Electroshock-Induced Seizures in Mice. AB - BACKGROUND/AIMS: The aim of this study was to determine the effects of umbelliferone (7-hydroxycoumarin; UMB) on the anticonvulsant potency of four classical antiepileptic drugs (carbamazepine (CBZ), phenytoin (PHT), phenobarbital (PB) and valproate (VPA)) in the mouse maximal electroshock-induced seizure (MES) model. RESULTS: UMB administered systemically intraperitoneally (ip) in a dose of 150 mg/kg significantly elevated the threshold for maximal electroconvulsions (p < 0.05) in mice. Moreover, UMB (150 mg/kg) co-administered with PB and VPA significantly enhanced the anticonvulsant potency of these drugs by reducing their median effective doses (ED50 values) from 35.39 to 21.78 mg/kg (p < 0.01) for PB, and from 281.4 to 215.5 mg/kg (p < 0.01) for VPA. In contrast, UMB (150 mg/kg, ip) had no significant effect on the antiseizure activity of CBZ and PHT in the mouse MES model. Neither total brain PB, nor total brain VPA concentrations were altered after ip administration of UMB, indicating a pharmacodynamic nature of interactions between the tested drugs. CONCLUSIONS: The selective potentiation of the anticonvulsant potency of PB and VPA by UMB, and lack of any pharmacokinetic interactions between drugs, make the combinations of UMB with PB or VPA worthy of consideration for epileptic patients who are refractory to standard antiepileptic treatment. PMID- 26279466 TI - A scenario for magnonic spin-wave traps. AB - Spatially resolved measurements of the magnetization dynamics on a thin CoFeB film induced by an intense laser pump-pulse reveal that the frequencies of resulting spin-wave modes depend strongly on the distance to the pump center. This can be attributed to a laser generated temperature profile. We determine a shift of 0.5 GHz in the spin-wave frequency due to the spatial thermal profile induced by the femtosecond pump pulse that persists for up to one nanosecond. Similar experiments are presented for a magnonic crystal composed of a CoFeB-film based antidot lattice with a Damon Eshbach mode at the Brillouin zone boundary and its consequences are discussed. PMID- 26279467 TI - Investigating the cytotoxicity of iron oxide nanoparticles in in vivo and in vitro studies. AB - In recent years, iron oxide nanorods find a lot of applications including drug delivery, cell separation, hyperthermia and magnetic resonance imaging. In this study the cytotoxicity of iron oxide nanorods was evaluated based on mouse fibroblast cell behavior and wistar rat's liver and kidney function. At first for modification, nanorods were added to Dulbecco's modified Eagle's medium (DMEM) which contained a lot of sources of vitamins, amino acids, proteins in Fetal Bovine Serum (FBS). The MTT assay was employed for evaluating the toxic effects of 200 and 400 MUg/mL modified and non-modified iron oxide nanorods on L929 mouse fibroblast cells in a 24h period. Changes in cell granularity and size as well as cell cycle were investigated using flow cytometry. Moreover liver and kidney function test and serum iron level measurement were performed 24h after the injection of modified iron oxide nanorods via the tail peripheral vein of wistar rats. Results indicated that greater concentration of modified iron oxide nanorods had no significant effect on cell viability while greater concentration of non-modified iron oxide nanorods significantly decreased cell viability. Modified iron oxide nanorods did not have significant effects on cell cycle. The results of liver and kidney function tests did not differ significantly while a significant increase in serum iron level was observed. After H&E staining of slices, there were no changes on morphology of rat's kidney and liver cells. This study suggests that short-time use of 200 and 400 MUg/mL iron oxide nanorods are probably safe. Further studies are needed for investigation of toxic effects of different concentrations, coatings, and exposure time periods of iron oxide nanorods. PMID- 26279468 TI - Major depressive disorder: reification and (maybe) rheostasis. AB - The heterogeneity of clinical syndromes subsumed by diagnostic criteria for major depressive disorder (MDD) is regarded by some as a reason to abandon or modify the criteria. However, heterogeneity may be unavoidable because of the biopsychosocial complexity of depression. MDD may be characterised by complexities that cannot be distilled down to any brief set of diagnostic criteria. Psychiatrists and psychiatric epidemiologists may need to revise their expectations of this diagnosis in order to avoid over-estimating its ability to guide the selection of treatments and prediction of prognosis. An opposing perspective is that of reification, in which the diagnosis is viewed as being more real than it really is. The concept of rheostasis may help to explain some features of this condition, such as why major depressive episodes sometimes seem understandable or even adaptive (e.g. in the context of bereavement) whereas at other times such episodes are inexplicable and maladaptive. PMID- 26279469 TI - Start me up! Recurrent ventricular tachydysrhythmias following intentional concentrated caffeine ingestion. AB - CONTEXT: Nearly pure caffeine is sold as a "dietary supplement," with instructions to ingest 1/64th to 1/16th of one teaspoon (50-200 mg). We report a patient with refractory cardiac dysrhythmias treated with defibrillation, beta adrenergic blockade, and hemodialysis to highlight concentrated caffeine's dangers. CASE DETAILS: A 20-year-old woman presented with severe agitation, tremor, and vomiting approximately 1-2 h after suicidal ingestion of concentrated caffeine (powder and tablets). Within minutes, ventricular fibrillation commenced. Defibrillation, intubation, and amiodarone administration achieved return of spontaneous circulation (ROSC). Shortly thereafter, she developed pulseless ventricular tachycardia (VTach), with ROSC after defibrillation and lidocaine. She subsequently experienced 23 episodes of pulseless VTach, each responsive to defibrillation. Activated charcoal was administered via orogastric tube. An esmolol infusion was started. Hemodialysis was initiated once she was hemodynamically stable. She was extubated the following day, continued on oral metoprolol, and transferred to psychiatry on hospital day seven, achieving full neurological recovery. Serum caffeine concentrations performed approximately six and 18 h post-ingestion (pre/post-dialysis) were 240.8 mcg/mL and 150.7 mcg/mL. DISCUSSION: Severe caffeine toxicity can produce difficult to treat, life threatening dysrhythmias. Concentrated caffeine, marketed for dietary supplementation, presents a substantial public health risk that demands action to limit consumer availability. PMID- 26279471 TI - A qualitative exploration of parental experiences of stigma while living with HIV in Bangladesh. AB - With much of the focus on the "risk" groups, families have often been less studied in HIV research. Further, because of a focus on the aetiology and epidemiology of HIV, the social impacts associated with HIV on families and neighbours are sometimes overlooked. This study examined parental experiences of stigma and discrimination while living with HIV within a family context in Bangladesh. A qualitative research design using a grounded theory approach was used for this research. Data was collected through in-depth interviews with 19 HIV-positive parents, recruited with the support of two self-help groups of HIV positive people, in two settings namely Khulna and Dhaka in Bangladesh. The findings indicate that HIV-positive parents held the view that they continue to experience significant stigma and their narratives clearly show how this affected them and their children. A range of informal practices were enacted in everyday contexts by extended family and community members to identify, demarcate and limit the social interaction of HIV-positive parents. Parents highlighted a number of factors including negative thoughts and behaviours, rejection, isolation and derogatory remarks as manifestations of stigma and discrimination, impacting upon them and their children because of their association with HIV. PMID- 26279470 TI - Photodynamic activation as a molecular switch to promote osteoblast cell differentiation via AP-1 activation. AB - In photodynamic therapy (PDT), cells are impregnated with a photosensitizing agent that is activated by light irradiation, thereby photochemically generating reactive oxygen species (ROS). The amounts of ROS produced depends on the PDT dose and the nature of the photosensitizer. Although high levels of ROS are cytotoxic, at physiological levels they play a key role as second messengers in cellular signaling pathways, pluripotency, and differentiation of stem cells. To investigate further the use of photochemically triggered manipulation of such pathways, we exposed mouse osteoblast precursor cells and rat primary mesenchymal stromal cells to low-dose PDT. Our results demonstrate that low-dose PDT can promote osteoblast differentiation via the activation of activator protein-1 (AP 1). Although PDT has been used primarily as an anti-cancer therapy, the use of light as a photochemical "molecular switch" to promote differentiation should expand the utility of this method in basic research and clinical applications. PMID- 26279472 TI - In vivo micro-scale tomography of ciliary behavior in the mammalian oviduct. AB - Motile cilia in the mammalian oviduct play a key role in reproduction, such as transporting fertilized oocytes to the uterus for implantation. Due to their small size (~5-10 MUm in length and ~300 nm in diameter), live visualization of cilia and their activity in the lumen of the oviduct through tissue layers represents a major challenge not yet overcome. Here, we report a functional low coherence optical imaging technique that allows in vivo depth-resolved mapping of the cilia location and cilia beat frequency (CBF) in the intact mouse oviduct with micro-scale spatial resolution. We validate our approach with widely-used microscopic imaging methods, present the first in vivo mapping of the oviduct CBF in its native context, and demonstrate the ability of this approach to differentiate CBF in different locations of the oviduct at different post conception stages. This technique opens a range of opportunities for live studies in reproductive medicine as well as other areas focused on cilia activity and related ciliopathies. PMID- 26279473 TI - Arid1a inactivation in an Apc- and Pten-defective mouse ovarian cancer model enhances epithelial differentiation and prolongs survival. AB - Inactivation of the ARID1A tumour suppressor gene is frequent in ovarian endometrioid (OEC) and clear cell (OCCC) carcinomas, often in conjunction with mutations activating the PI3K-AKT and/or canonical Wnt signalling pathways. Prior work has shown that conditional bi-allelic inactivation of the Apc and Pten tumour suppressor genes in the mouse ovarian surface epithelium (OSE) promotes outgrowth of tumours that reflect the biological behaviour and gene expression profiles of human OECs harbouring comparable Wnt and PI3K-AKT pathway defects, although the mouse tumours are more poorly differentiated than their human tumour counterparts. We found that conditional inactivation of one or both Arid1a alleles in OSE concurrently with Apc and Pten inactivation unexpectedly prolonged the survival of tumour-bearing mice and promoted striking epithelial differentiation of the cancer cells, resulting in morphological features akin to those in human OECs. Enhanced epithelial differentiation was linked to reduced expression of the mesenchymal markers N-cadherin and vimentin, and increased expression of the epithelial markers Crb3 and E-cadherin. Global gene expression profiling showed enrichment for genes associated with mesenchymal-epithelial transition in the Arid1a-deficient tumours. We also found that an activating (E545K) Pik3ca mutation, unlike Pten inactivation or Pik3ca H1047R mutation, cannot cooperate with Arid1a loss to promote ovarian cancer development in the mouse. Our results indicate that the Arid1a tumour suppressor gene has a key role in regulating OEC differentiation, and paradoxically the mouse cancers with more initiating tumour suppressor gene defects had a less aggressive phenotype than cancers arising from fewer gene alterations. Microarray data have been deposited in NCBI's Gene Expression Omnibus (GSE67695). PMID- 26279474 TI - Dynamics of a deep-water seagrass population on the Great Barrier Reef: annual occurrence and response to a major dredging program. AB - Global seagrass research efforts have focused on shallow coastal and estuarine seagrass populations where alarming declines have been recorded. Comparatively little is known about the dynamics of deep-water seagrasses despite evidence that they form extensive meadows in some parts of the world. Deep-water seagrasses are subject to similar anthropogenic threats as shallow meadows, particularly along the Great Barrier Reef lagoon where they occur close to major population centres. We examine the dynamics of a deep-water seagrass population in the GBR over an 8 year period during which time a major capital dredging project occurred. Seasonal and inter-annual changes in seagrasses were assessed as well as the impact of dredging. The seagrass population was found to occur annually, generally present between July and December each year. Extensive and persistent turbid plumes from a large dredging program over an 8 month period resulted in a failure of the seagrasses to establish in 2006, however recruitment occurred the following year and the regular annual cycle was re-established. Results show that despite considerable inter annual variability, deep-water seagrasses had a regular annual pattern of occurrence, low resistance to reduced water quality but a capacity for rapid recolonisation on the cessation of impacts. PMID- 26279476 TI - Keap1-Nrf2 regulated redox signaling in utero: Priming of disease susceptibility in offspring. AB - Intrauterine exposure to gestational diabetes, pre-eclampsia or intrauterine growth restriction alters the redox status of the developing fetus. Such pregnancy-related diseases in most cases do not have a readily identifiable genetic cause, and epigenetic 'priming' mechanisms in utero may predispose both mother and child to later-life onset of cardiovascular and metabolic diseases. The concept of 'fetal programing' or 'developmental priming' and its association with an increased risk of disease in childhood or adulthood has been reviewed extensively. This review focuses on adaptive changes in the in utero redox environment during normal pregnancy and the consequences of alterations in redox control associated with pregnancies characterized by oxidative stress. We evaluate the evidence that the Keap1-Nrf2 pathway is important for protecting the fetus against adverse conditions in utero and may itself be subject to epigenetic priming, potentially contributing to an increased risk of vascular disease and insulin resistance in later life. PMID- 26279475 TI - Multimodal Chemosensory Circuits Controlling Male Courtship in Drosophila. AB - Throughout the animal kingdom, internal states generate long-lasting and self perpetuating chains of behavior. In Drosophila, males instinctively pursue females with a lengthy and elaborate courtship ritual triggered by activation of sexually dimorphic P1 interneurons. Gustatory pheromones are thought to activate P1 neurons but the circuit mechanisms that dictate their sensory responses to gate entry into courtship remain unknown. Here, we use circuit mapping and in vivo functional imaging techniques to trace gustatory and olfactory pheromone circuits to their point of convergence onto P1 neurons and reveal how their combined input underlies selective tuning to appropriate sexual partners. We identify inhibition, even in response to courtship-promoting pheromones, as a key circuit element that tunes and tempers P1 neuron activity. Our results suggest a circuit mechanism in which balanced excitation and inhibition underlie discrimination of prospective mates and stringently regulate the transition to courtship in Drosophila. PMID- 26279477 TI - Determination of Specificity and Biochemical Characteristics of Neutral Protease Isolated from Myceliophthora thermophila. AB - Proteases hydrolyze polypeptides to release peptides and/or amino acids. This subclass of enzymes is among those with the most sales worldwide, particularly those produced by microorganisms. Proteases may be applied in the several industries, including the food industry, leather, detergents, and bioremediation. Myceliophthora thermophila protease was produced by a submerged bioprocess and then purified 185-fold by anion exchange and hydrophobic chromatography with a 37% yield. The molecular mass was estimated at 36.2 kDa, and mass spectrometry identified two sequences: GVVANMSLGGSYSASINNAAAALVR and STGNAAITGVPSGTTNR. The isolated protein was characterized biochemically, showed an optimum pH of 6.5 and optimum temperature of 45 degrees C, and stability at wide range of pH and temperatures and in the presence of reducing agents and some surfactants. Kinetic assays for this enzyme showed a greater catalytic efficiency when the substrate had alanine at position P'2. The protease presented characteristics that may be of interest to many industrial areas. PMID- 26279478 TI - Theoretical Study of Large-Angle Bending Transport of Microparticles by 2D Acoustic Half-Bessel Beams. AB - Conventional microparticle transports by light or sound are realized along a straight line. Recently, this limit has been overcome in optics as the growing up of the self-accelerating Airy beams, which are featured by many peculiar properties, e.g., bending propagation, diffraction-free and self-healing. However, the bending angles of Airy beams are rather small since they are only paraxial solutions of the two-dimensional (2D) Helmholtz equation. Here we propose a novel micromanipulation by using acoustic Half-Bessel beams, which are strict solutions of the 2D Helmholtz equation. Compared with that achieved by Airy beams, the bending angle of the particle trajectory attained here is much steeper (exceeding 90(o)). The large-angle bending transport of microparticles, which is robust to complex scattering environment, enables a wide range of applications from the colloidal to biological sciences. PMID- 26279479 TI - Management of Teeth with Persistent Apical Periodontitis after Root Canal Treatment Using Regenerative Endodontic Therapy. AB - Regenerative endodontic therapy (RET) is currently used to treat immature teeth with necrotic pulp and/or apical periodontitis. However, recently RET has been used to treat mature teeth with necrotic pulp and/or apical periodontitis and resulted in regression of clinical signs and/or symptoms and resolution of apical periodontitis. The purpose of this case report was to describe the potential of using RET to treat 2 mature teeth with persistent apical periodontitis after root canal therapy using RET. Two male patients, one 26-year old and another 12-year old, presented for retreatment of persistent apical periodontitis after root canal treatment of 2 mature teeth (#9 and #19). The gutta-percha fillings in the canals of teeth #9 and #19 were removed with Carvene gutta-percha solvent (Prevest DenPro, Jammu, India) and ProTaper Universal rotary retreatment files (Dentsply Maillefer, Ballaigues, Switzerland). The canals of both teeth were further chemomechanically debrided with rotary retreatment files and copious amounts of sodium hypochlorite irrigation and dressed with Metapaste (Meta Biomed, Chungbuk, Korea). RET was performed on teeth #9 and #19. Periapical bleeding was provoked into the disinfected root canals. The blood clots were covered with mineral trioxide aggregate plugs, and the access cavities were restored with intermediate restorative material. Teeth #9 and #19 showed regression of clinical signs and/or symptoms and healing of apical periodontitis after 13-month and 14-month follow-ups, respectively. Tooth #9 revealed narrowing of the canal space and apical closure by deposition of hard tissue. RET has the potential to be used to retreat teeth with persistent apical periodontitis after root canal therapy. PMID- 26279480 TI - Instrumental variable methods in clinical research. PMID- 26279481 TI - Percutaneous aortic and mitral valve implantation. Is it ready to match the results of contemporary surgical valve replacement? PMID- 26279482 TI - Comparison of basal insulin therapies with regard to the risk of acute myocardial infarction in patients with type 2 diabetes: an observational cohort study. AB - AIMS: To assess the risk of acute myocardial infarction (AMI) in patients with type 2 diabetes mellitus treated with long-acting insulin analogues in comparison with other basal insulin therapy. METHODS: We used German insurance claims data from the years 2004-2009 to conduct a study in a retrospective cohort of patients with type 2 diabetes. Naive insulin users were defined as patients who had an insulin-free history before the first prescription of long-acting analogue insulin, human NPH insulin or premixed insulin and who were pretreated with oral antidiabetic drugs. Adjusted hazard ratios (HRs) of AMI and corresponding 95% confidence intervals (CIs) were calculated using sex-stratified Cox models. Propensity-score-matched analyses were conducted as sensitivity analyses. RESULTS: We identified 21,501 new insulin users. Patients treated with premixed insulin were older than patients treated with analogue or NPH insulin (mean age 70.7 vs. 64.1 and 61.6 years, respectively) and had more comorbidities. Regarding the risk of AMI, adjusted HRs showed no statistically significant difference between NPH and analogue insulin (HR 0.94, 95% CI 0.74-1.19), but a higher risk for premixed than for analogue insulin (HR 1.27, 95% CI 1.02-1.58). Contrary to the primary analysis, the propensity-score-matched analysis did not show an increased risk for premixed insulin. CONCLUSIONS: In contrast to a former database study, no difference was observed for the risk of AMI between long acting analogue and NPH insulin in this study. Neither long-acting analogue insulin nor premixed insulin appears to be associated with AMI in patients with type 2 diabetes. PMID- 26279483 TI - Fetal anemia caused by the Guadalajara variant of G6PD deficiency. PMID- 26279484 TI - Genetic analysis in retinoblastoma and peripheral blood correlation. AB - OBJECTIVE: To determine the importance of intratumoral genetic analysis in the diagnosis of germ-line mutations in patients with retinoblastoma. To underline the importance of performing these genetic tests in every case of retinoblastoma. METHOD: Intratumoral genetic analysis of RB1 mutation was performed on 17 enucleated eyes that were non-responsive to conservative treatment. Patients had no family history of retinoblastoma, and lesions were always single. The identified mutations were then also studied in peripheral blood analysis. RESULTS: There were 12 (70.6%) cases with positive results in intratumoral analysis. In 8 cases (47.1%) mutation of both RB1 alelli were detected, and in 4 (23.5%) cases only one allele was found mutated. In 5 patients (29.4%) no mutation was identified. In the first hit, mutations comprised 7 frameshift or nonsense and 2 splice, whereas in the second hit, one splice mutation, 2 nonsense and 8 loss of heterozygosity were identified. Among 6 patients where intratumoral analysis detected a single mutation associated with a loss of heterozygosity, the peripheral blood analysis was able to detect the same mutation in 3 cases (50%). CONCLUSIONS: Intratumoral genetic analysis of sporadic retinoblastoma can detect germ-line mutations. These patients are at higher risk of bilateralization and development of second tumors or trilateral retinoblastoma. Genetic screening is recommended in every patient diagnosed with retinoblastoma. PMID- 26279485 TI - Maternal piRNAs Are Essential for Germline Development following De Novo Establishment of Endo-siRNAs in Caenorhabditis elegans. AB - The Piwi-piRNA pathway represents a germline-specific transposon-defense system. C. elegans Piwi, prg-1, is a non-essential gene and triggers a secondary RNAi response that depends on mutator genes, endo-siRNAs (22G-RNAs), and the 22G-RNA binding Argonaute protein HRDE-1. Interestingly, silencing of PRG-1 targets can become PRG-1 independent. This state, known as RNAe, is heritable and depends on mutator genes and HRDE-1. We studied how the transgenerational memory of RNAe and the piRNA pathway interact. We find that maternally provided PRG-1 is required for de novo establishment of 22G-RNA populations, especially those targeting transposons. Strikingly, attempts to re-establish 22G-RNAs in absence of both PRG 1 and RNAe memory result in severe germline proliferation defects. This is accompanied by a disturbed balance between gene-activating and -repressing 22G RNA pathways. We propose a model in which CSR-1 prevents the loading of HRDE-1 and in which both PRG-1 and HRDE-1 help to keep mutator activity focused on the proper targets. PMID- 26279486 TI - Cortical Tension Allocates the First Inner Cells of the Mammalian Embryo. AB - Every cell in our body originates from the pluripotent inner mass of the embryo, yet it is unknown how biomechanical forces allocate inner cells in vivo. Here we discover subcellular heterogeneities in tensile forces, generated by actomyosin cortical networks, which drive apical constriction to position the first inner cells of living mouse embryos. Myosin II accumulates specifically around constricting cells, and its disruption dysregulates constriction and cell fate. Laser ablations of actomyosin networks reveal that constricting cells have higher cortical tension, generate tension anisotropies and morphological changes in adjacent regions of neighboring cells, and require their neighbors to coordinate their own changes in shape. Thus, tensile forces determine the first spatial segregation of cells during mammalian development. We propose that, unlike more cohesive tissues, the early embryo dissipates tensile forces required by constricting cells via their neighbors, thereby allowing confined cell repositioning without jeopardizing global architecture. PMID- 26279487 TI - piRNAs and piRNA-Dependent siRNAs Protect Conserved and Essential C. elegans Genes from Misrouting into the RNAi Pathway. AB - piRNAs silence foreign genes, such as transposons, to preserve genome integrity, but they also target endogenous mRNAs by mechanisms that are poorly understood. Caenorhabditis elegans piRNAs interact with both transposon and nontransposon mRNAs to initiate sustained silencing via the RNAi pathway. To assess the dysregulation of gene silencing caused by lack of piRNAs, we restored RNA silencing in RNAi-defective animals in the presence or absence of piRNAs. In the absence of piRNAs and a cellular memory of piRNA activity, essential and conserved genes are misrouted into the RNAi pathway to produce siRNAs that bind the nuclear Argonaute HRDE-1, resulting in dramatic defects in germ cell proliferation and function such that the animals are sterile. Inactivation of RNAi suppresses sterility, indicating that aberrant siRNAs produced in the absence of piRNAs target essential genes for silencing. Thus, by reanimating RNAi, we uncovered a role for piRNAs in protecting essential genes from RNA silencing. PMID- 26279488 TI - Evaluation of tricuspid annular plane systolic excursion measured with cardiac MRI in children with tetralogy of Fallot. AB - BACKGROUND: Aneurysmal dilation of the right ventricular outflow tract complicates assessment of right ventricular function in patients with repaired tetralogy of Fallot. Tricuspid annular plane systolic excursion is commonly used to estimate ejection fraction. We hypothesised that tricuspid annular plane systolic excursion measured by cardiac MRI approximates global and segmental right ventricular function, specifically right ventricular sinus ejection fraction, in children with repaired tetralogy of Fallot. METHODS: Tricuspid annular plane systolic excursion was measured retrospectively on cardiac MRIs in 54 patients with repaired tetralogy of Fallot. Values were compared with right ventricular global, sinus, and infundibular ejection fractions. Tricuspid annular plane systolic excursion was indexed to body surface area, converted into a fractional value, and converted into published paediatric Z-scores. RESULTS: Tricuspid annular plane systolic excursion measurements had good agreement between observers. Right ventricular ejection fraction did not correlate with the absolute or indexed tricuspid annular plane systolic excursion and correlated weakly with fractional tricuspid annular plane systolic excursion (r=0.41 and p=0.002). Segmental right ventricular function did not appreciably improve correlation with any of the tricuspid annular plane systolic excursion measures. Paediatric Z-scores were unable to differentiate patients with normal and abnormal right ventricular function. CONCLUSIONS: Tricuspid annular plane systolic excursion measured by cardiac MRI correlates poorly with global and segmental right ventricular ejection fraction in children with repaired tetralogy of Fallot. Tricuspid annular plane systolic excursion is an unreliable approximation of right ventricular function in this patient population. PMID- 26279489 TI - Correlation Between Tinnitus and Petrotympanic Fissure Status Among Patients With Temporomandibular Joint Dysfunction. AB - PURPOSE: The objective of this study was to evaluate the correlation between tinnitus and petrotympanic fissure (PTF) subtypes in patients diagnosed with temporomandibular joint dysfunction (TMD). MATERIALS AND METHODS: One hundred patients with TMD (50 with tinnitus, 50 without tinnitus) were evaluated retrospectively using cone-beam computed tomography (CBCT). CBCT images were analyzed according to PTF subtype diagnosis (types 1 to 3). PTF structure was classified as type 1 (wide tubular formation), type 2 (double conical structure), or type 3 (single conical structure). RESULTS: Although there was a negative correlation between tinnitus and PTF type (P < .001), there was no correlation between age and tinnitus or between age and subtype of PTF. There was no significant association between gender and tinnitus or PTF type (P > .05). CONCLUSIONS: A short, wide PTF (type 1) might be associated with an increased incidence of tinnitus in patients with TMD. PMID- 26279490 TI - McGrath Video Laryngoscopy Facilitates Routine Nasotracheal Intubation in Patients Undergoing Oral and Maxillofacial Surgery: A Comparison With Macintosh Laryngoscopy. AB - PURPOSE: The McGrath video laryngoscope (VL) offers excellent laryngoscopic views and increases the success rate of orotracheal intubation in patients with normal and difficult airways. The purpose of this randomized controlled trial was to compare the McGrath VL with the Macintosh laryngoscope to investigate the efficacy of the McGrath VL for routine nasotracheal intubation in patients with an expected normal airway. MATERIALS AND METHODS: To address the research purpose, the efficacy of the McGrath VL for routine nasotracheal intubation was compared with that of the Macintosh laryngoscope. The predictor variable was the laryngoscopic technique (McGrath VL vs Macintosh laryngoscope). The outcome variables were the time to successful intubation, laryngoscopic views before and after optimal external laryngeal manipulation (OELM), use of Magill forceps, ease of intubation, and severity of oropharyngeal bleeding. RESULTS: Data from 35 patients undergoing oral and maxillofacial surgery were assessed. The time to intubation was 10.5 seconds shorter in the McGrath group than in the Macintosh group (34.4 +/- 13.7 vs 44.9 +/- 15.6 seconds; P = .004). The incidence of grade 1 glottic view before OELM was higher in the McGrath group than in the Macintosh group (83 vs 57%; P = .019). The frequency of Magill forceps use was lower in the McGrath group than in the Macintosh group (6 vs 34%; P = .003). CONCLUSION: McGrath VL facilitates routine nasotracheal intubation in expected normal airways by providing a shorter intubation time and better laryngoscopic views compared with the Macintosh laryngoscope. PMID- 26279491 TI - What do mathematical models tell us about killing rates during HIV-1 infection? AB - Over the past few decades the extent to which cytotoxic T lymphocytes (CTLs) control human immunodeficiency virus (HIV) replication has been studied extensively, yet their role and mode of action remain controversial. In some studies, CTLs were found to kill a large fraction of the productively infected cells relative to the viral cytopathicity, whereas in others CTLs were suggested to kill only a small fraction of infected cells. In this review, we compile published estimates of CTL-mediated death rates, and examine whether these studies permit determining the rate at which CTLs kill HIV-1 infected cells. We highlight potential misinterpretations of the CTL-killing rates from the escape rates of mutants, and from perturbations of the steady state viral load during chronic infection. Our major conclusion is that CTL-mediated killing rates remain unknown. But contrary to current consensus, we argue that killing rates higher than one per day are perfectly consistent with the experimental data, which would imply that the majority of the productively infected cells could still die from CTL-mediated killing rather than from viral cytopathicity. PMID- 26279492 TI - Forkhead box O transcription factors as possible mediators in the development of major depression. AB - Forkhead box O (FoxO) transcription factors play important roles in cellular physiology and biology. Recent findings indicate that FoxOs are also involved in the development of major depressive disorder. Alterations in the upstream molecules of FoxOs, such as brain derived neurotrophic factor or protein kinase B, have been linked to depression. Antidepressants, such as imipramine and venlafaxine, modify the FoxOs phosphorylation. Furthermore, FoxOs could be regulated by serotonin and norepinephrine receptor signaling as well as the hypothalamic-pituitary-adrenal axis, all of which are involved in the pathogenesis of depression. FoxOs also regulate neuronal morphology, synaptogenesis and adult hippocampal neurogenesis, which are viewed as candidate mechanisms for the etiology of depression. In this review, we emphasize the possible roles of FoxOs during the development of depression and make some strategic recommendations for future research. We propose that FoxOs and its signaling pathways may constitute potential therapeutic targets in the treatment of depression. PMID- 26279493 TI - The Effect of Exercise on Vascular Function and Stiffness in Type 2 Diabetes: A Systematic Review and Meta-analysis. AB - Deterioration of the structure and function of the vascular system is the underlying feature in cardiovascular disease (CVD), which is the highest cause of mortality in type 2 diabetes (T2D). Studies assessing the effect of exercise on vascular function and stiffness have used different measurement techniques and small cohorts, making it difficult to conclude on the overall efficacy of exercise on these outcomes. The aim of this study was to assess the effect of exercise on vascular function and stiffness in T2D. Electronic database searches were performed in AMED, MEDLINE, MEDLINE Daily Update, PREMEDLINE, SPORTDiscus, CINAHL, EMBASE and Web of Science. The effect size (ES), and 95% confidence intervals (CIs) of eligible studies were calculated. Pooled estimates of the effect of aerobic exercise (AEx) on vascular function and stiffness, using ES, were obtained. Results show that AEx led to a near-significant reduction in PWV (ES = -0.472; 95% CI: -0.949 to 0.005; P = 0.052), a significant reduction in EID (ES = 0.416, 95% CI: 0.062 to 0.769; P= 0.021), and a non-significant benefit in FMD measures. There were limited studies using resistance training or in combination with aerobic exercise, to assess a pooled effect on vascular function or stiffness. These data suggest that aerobic exercise training should be used as a primary treatment strategy for improving vascular smooth muscle function as measured by EID in individuals with T2D. There is currently insufficient evidence concerning the efficacy of regular exercise for improving vascular function and stiffness as measured by FMD and PWV. PMID- 26279494 TI - The function of the self-attention network. AB - This commentary links Humphrey and Sui's proposed Self-attention Network (SAN) to the memory advantage associated with self-relevant information (i.e., the self reference effect). Articulating this link elucidates the functional quality of the SAN in ensuring that information of potential importance to self is not lost. This adaptive system for self-processing mirrors the cognitive response to threat stimuli, which also elicit attentional biases and produce characteristically enhanced, episodic representations in memory. Understanding the link between the SAN and memory is key to comprehending more broadly the operation of the self in cognition. PMID- 26279495 TI - Animal models of erectile dysfunction. AB - Erectile dysfunction (ED) is a prevalent male sexual dysfunction with profound adverse effects on the physical and the psychosocial health of men and, subsequently, on their partners. The expanded use of various types of rodent models has produced some advances in the study of ED, and neurophysiological studies using various animal models have provided important insights into human sexual dysfunction. At present, animal models play a key role in exploring and screening novel drugs designed to treat ED. PMID- 26279496 TI - Biomarkers to assess donor-reactive T-cell responses in kidney transplant patients. AB - Different to antibody-mediated rejection (ABMR), T-cell mediated rejection (TCMR) still unpredictably occurs after kidney transplantation in a great part because of a poor immunologic evaluation of the cellular allogeneic immune response. However, in the last years, important efforts have focused on the development of novel and more sensitive assays to monitor T-cell alloimmune responses at different biological levels that may improve the understanding of the functional status of the cellular immune compartment in patients undergoing organ transplantation. In this direction, immune assays evaluating T-cell proliferation, intracellular ATP release, multiparameter flow cytometry, profiling T-cell receptor repertoires and measurements of frequencies of cytokine producing T-cells using an IFN-gamma enzyme-linked immunospot assay (IFN-gamma ELISPOT) have been reported showing interesting associations between the cellular alloimmune response and kidney transplant outcomes. In summary, an important progress has been made in the assessment of alloreactive T-cell responses in the context of organ transplantation using novel immune assays at different biological levels. However, there is an urgent need for prospective, randomized clinical studies to validate these encouraging preliminary data to ultimately introduce them in current clinical practice for refining current immune-risk stratification in kidney transplantation. PMID- 26279497 TI - Exposure to unwanted intrusions, neutralizing and their effects on self-worth and obsessive-compulsive phenomena. AB - BACKGROUND: Although there is a growing body of literature to support the importance of understanding self processes in the experience of obsessive compulsive disorder (OCD), no experimental research has directly examined the relationship between self-construals and phenomena central to OCD. The current study examined the effect that unwanted intrusions and neutralizing responses have on self-worth, distress and urge to neutralize. METHODS: After listening to repeated audio recordings of idiosyncratic unwanted intrusions, a combined nonclinical and clinical OCD sample were asked to respond with either their chosen neutralizing strategy (experimental) or a refocus counting strategy (control). Each condition comprised of a 12-min responding period (respond) followed by an equivalent non-response period (listen). Participants completed each condition, and were randomly allocated into the condition completed first. Ratings of discomfort, urge to neutralize, and self-worth were measured throughout. RESULTS: Neutralizing and refocussing responses were both associated with decreases in discomfort and higher self-worth. The expected rebound effect for discomfort and urge to neutralize for the listen period after neutralizing was found. LIMITATIONS: Methodological problems lead to missing data, although this was corrected with the use of Multi Level Modelling (MLM) analysis on a combined sample. The small clinical sample meant that comparison between the two populations was not possible. CONCLUSIONS: Findings support cognitive accounts that neutralizing is involved in the development and maintenance of OCD, and suggest that neutralizing is a purposeful response aimed to help reinstate self worth. Implications and directions for future research are discussed. PMID- 26279498 TI - Precipitation and surface adsorption of metal complexes during electropolishing. Theory and characterization with X-ray nanotomography and surface tension isotherms. AB - Electropolishing of metals often leads to supersaturation conditions resulting in precipitation of complex compounds. The solubility diagrams and Gibbs adsorption isotherms of the electropolishing products are thus very important to understand the thermodynamic mechanism of precipitation of reaction products. Electropolishing of tungsten wires in aqueous solutions of potassium hydroxide is used as an example illustrating the different thermodynamic scenarios of electropolishing. Electropolishing products are able to form highly viscous films immiscible with the surrounding electrolyte or porous shells adhered to the wire surface. Using X-ray nanotomography, we discovered a gel-like phase formed at the tungsten surface during electropolishing. The results of these studies suggest that the electropolishing products can form a rich library of compounds. The surface tension of the electrolyte depends on the metal oxide ions and alkali metal complexes. PMID- 26279499 TI - Leukocyte esterase in the diagnosis of shoulder periprosthetic joint infection. AB - BACKGROUND: Shoulder periprosthetic joint infection (PJI) is difficult to diagnose with traditional methods. Leukocyte esterase (LE) has recently proven to be reliable in knee arthroplasty; however, its value in the shoulder has not been explored. We hypothesized that LE would display high sensitivity and specificity in shoulder PJI. METHODS: Two groups were prospectively evaluated: 45 primary and 40 revision shoulder arthroplasties. Synovial fluid and soft tissue cultures were obtained at surgery. Synovial fluid was evaluated with LE test strips. Any aspiration that contained erythrocytes was centrifuged and retested. Shoulder PJI was defined by modified Musculoskeletal Infection Society (MSIS) criteria. RESULTS: Of 5 primaries with positive tissue cultures (11%), only 1 was positive for LE. Of 16 revisions with positive cultures (40%), 4 had positive LE results. Among all patients with bacterial isolates, 6 aspirates were not interpretable (29%), despite centrifugation. LE had sensitivity of 25% and specificity of 75% to predict positive cultures in revisions. Ten revision patients met modified MSIS criteria for PJI. The sensitivity of LE in these patients was 30%, and the specificity was 67% (positive predictive value, 43%; negative predictive value, 83%). If bloody aspirates were considered positive, LE sensitivity in MSIS PJI increased to 60%, but the positive predictive value fell to 37.5%. CONCLUSION: LE is an unreliable diagnostic measure in shoulder PJI. The presence of erythrocytes within aspirates further decreased its accuracy. We conclude that LE should not be used for the routine identification of shoulder PJI. PMID- 26279500 TI - Risk factor detection for heart disease by applying text analytics in electronic medical records. AB - In the United States, about 600,000 people die of heart disease every year. The annual cost of care services, medications, and lost productivity reportedly exceeds 108.9 billion dollars. Effective disease risk assessment is critical to prevention, care, and treatment planning. Recent advancements in text analytics have opened up new possibilities of using the rich information in electronic medical records (EMRs) to identify relevant risk factors. The 2014 i2b2/UTHealth Challenge brought together researchers and practitioners of clinical natural language processing (NLP) to tackle the identification of heart disease risk factors reported in EMRs. We participated in this track and developed an NLP system by leveraging existing tools and resources, both public and proprietary. Our system was a hybrid of several machine-learning and rule-based components. The system achieved an overall F1 score of 0.9185, with a recall of 0.9409 and a precision of 0.8972. PMID- 26279501 TI - Awake right hemisphere brain surgery. AB - We report the indications and outcomes of awake right hemispheric brain surgery, as well as a rare patient with crossed aphasia. Awake craniotomies are often performed to protect eloquent cortex. We reviewed the medical records for 35 of 96 patients, in detail, who had awake right hemisphere brain operations. Intraoperative cortical mapping of motor and/or language function was performed in 29 of the 35 patients. A preoperative speech impairment and left hand dominance were the main indicators for awake right-sided craniotomies in patients with right hemisphere lesions. Four patients with lesion proximity to eloquent areas underwent awake craniotomies without cortical mapping. In addition, one patient had a broncho-pulmonary fistula, and another had a recent major cardiac procedure that precluded awake surgery. An eloquent cortex representation was identified in 14 patients (48.3%). Postoperatively, seven of 17 patients (41.1%) who presented with weakness, experienced improvements in their motor functions, 11 of 16 (68.7%) with seizures became seizure-free, and seven of nine (77.7%) with moderate to severe headaches and one of two with a visual field deficit improved significantly. There were also improvements in speech and language functions in all patients who presented with speech difficulties. A right sided awake craniotomy is an excellent option for left handed patients, or those with right sided cortical lesions that result in preoperative speech impairments. When combined with intraoperative cortical mapping, both speech and motor function can be well preserved. PMID- 26279503 TI - First in human nanotechnology doxorubicin delivery system to target epidermal growth factor receptors in recurrent glioblastoma. AB - There are limited treatment options for patients with recurrent glioblastoma (GBM). The EnGeneIC delivery vehicle (EDV) is a novel nanocellular (minicell) compound which packages theoretically effective concentrations of chemotherapeutic drugs that are designed to target tumors via minicell-surface attached bispecific proteins (EnGeneIC, Lane Cove West, NSW, Australia). Epidermal growth factor receptor (EGFR) is overexpressed in 40-50% of patients with GBM and is a promising target for new therapeutics. (V)EDVDox contains doxorubicin (Dox) within the minicells and targets EGFR through Vectibix (V; Amgen Biologicals, Thousand Oaks, CA, USA). We conducted a first in human Phase I study of (V)EDVDox in adults with recurrent GBM expressing EGFR on immunohistochemistry, following standard therapy including radiation and temozolomide, to establish a safe maximum tolerated dose and determine a recommended Phase II dose (RPTD). (V)EDVDox was administered weekly in an 8week cycle, with dose escalation in successive cohorts of patients using a standard 3+3 design. In total, 14 patients were treated at three dose levels, and the RPTD was identified as 5*10(9)(V)EDVDox. Overall (V)EDVDox was well tolerated, with no dose limiting toxicity and no withdrawals from the study due to adverse events. The most common adverse events were nausea, fever, and chills or rigors, experienced in seven, five and five patients, respectively. Transient uncomplicated hypophosphatemia was seen in seven patients and was not dose related. Our results demonstrate that (V)EDVDox, up to a dose of 5*10(9)(V)EDVDox weekly, is well tolerated in patients with recurrent GBM. PMID- 26279502 TI - The kynurenine to tryptophan ratio as a prognostic tool for glioblastoma patients enrolling in immunotherapy. AB - We hypothesized that peripheral tryptophan (Trp) and/or kynurenine (Kyn) levels would provide prognostic value for physicians planning to enroll glioblastoma multiforme (GBM) patients in immunotherapy. GBM is the most common form of malignant glioma in adults. Despite aggressive surgical resection, irradiation and chemotherapy, patients with GBM have a median survival of only 14.6 months after diagnosis. This poor outcome has led to the search for more effective treatments, including immunotherapy. However, the identification of parameters that proactively stratify GBM patients who have the potential for therapeutic benefit has been challenging. Given recent observations demonstrating high indoleamine 2,3 dioxygenase 1 (IDO1) expression in GBM, the immunosuppressive impact of IDO1-mediated Trp catabolism, as well as active transport of Trp and the IDO1-downstream Trp catabolite, Kyn, across the blood brain barrier, we hypothesized that peripheral blood analysis of this pathway would provide diagnostic utility. When comparing individuals without tumors to GBM patients prior to surgical resection, or at the 48 hour (48 h) and ?10 week (10 w+) postoperative time points, Trp levels were significantly decreased (p<0.0002). Similarly, Kyn levels were decreased in the pre- and 48 h postoperative GBM patients (p<0.0001), while there was no difference between individuals without tumors and 10 w+ GBM patients. Interestingly, those 10 w+ patients with a high Kyn/Trp ratio (?9.5) had a mean overall survival (OS) of 23.6 +/- a standard error of 6.8 months, compared to an OS of 38.7 +/- 4.9 months for patients with lower Kyn/Trp values. Since the 10 w+ blood draw and analyses occurred prior to patient enrollment in the heat shock protein peptide complex-96 clinical trial, these novel data suggest that the late Kyn/Trp index may be a relevant clinical benchmark, providing prognostic value for GBM patients who are enrolled in immunotherapeutic regimens. PMID- 26279504 TI - Sister Mary Joseph's Nodule. PMID- 26279505 TI - Visual Diagnosis: Intraperitoneal Cerebrospinal Fluid Pseudocyst in an Adult Patient. PMID- 26279506 TI - Re: Not Another Boring Lecture: Let's Be the Guide on the Side. PMID- 26279507 TI - Endowed Faculty Positions in Academic Emergency Medicine: One Decade Later. AB - BACKGROUND: In 2004 and 2009, we examined the number of endowed faculty positions in academic departments of Emergency Medicine (ADEMs). OBJECTIVE: We sought to survey ADEMs regarding the number of endowed faculty positions and compare the results to the 2004 and 2009 studies. METHODS: A survey was e-mailed to the chairs of all ADEMs belonging to the Association of Academic Chairs of Emergency Medicine. We requested information on the following: the number of endowed chair and professorship positions; the amount required to fund; the amount allowed to be spent annually; the date established; and the source of funding. RESULTS: Eighty-nine chairs responded (100% response rate). Nineteen chairs reported 1 endowed chair position. One chair reported 2 such positions, and 2 chairs reported 3 positions. One chair reported 4 positions. In total, 23 ADEMs (25.8%) reported 31 endowed chair positions. For endowed professorships, 8 chairs reported 1 professorship each. Four chairs replied that they had 2 positions each and 2 chairs reported 3 positions each. A total of 14 ADEMS (15.7%) reported having 22 endowed professorships. The most common amount required to fund an endowed chair position was $2 million, and $1 million for an endowed professorship. The majority of ADEMs were allowed to spend 4% to 5% of the value of the endowment annually. CONCLUSION: Thirty ADEMs (33.7%) currently have an endowed position, compared to only 19 (26%) 5 years ago. Emergency Medicine now has a total of 53 endowed positions, compared to only 25 such positions in 2009 and just 9 endowed positions in 2004. PMID- 26279508 TI - Adrenal Mass Causing Secondary Hypertension. AB - BACKGROUND: Most hypertensive patients have essential (primary) hypertension; only 5% to 10% have a secondary cause. Two clinical characteristics suggestive of secondary hypertension are early onset (< 30 years of age) and severe hypertension (>180/110 mm Hg). When faced with these findings, clinicians should consider a secondary cause of hypertension. CASE REPORT: A 22-year-old woman being evaluated for asthma exacerbation in the emergency department was noted to have severe persistent hypertension. Additional evaluation revealed severe hypokalemia, metabolic alkalosis, and hypernatremia. The patient was admitted to the hospital for blood pressure management, electrolyte replacement, and further evaluation of presumed hyperaldosteronism. Diagnostic imaging revealed a large adrenal mass. Surgical resection was performed, leading to a diagnosis of hyperaldosteronism caused by adrenal carcinoma. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Secondary hypertension is far less common than essential hypertension; however, considering the large volume of patients seen in emergency departments, it is likely that some will have secondary hypertension. Emergency physicians should be aware of the clinical characteristics that suggest secondary hypertension so that the appropriate diagnostic and treatment pathways can be pursued. PMID- 26279509 TI - Regarding: Emergency Physicians May See Corneal Clouding Complicating a Corneal Transplant. PMID- 26279510 TI - Emergency Physicians May See Corneal Clouding Complicating a Corneal Transplant. PMID- 26279511 TI - "I'm Peeing Blood": A Case of Traumatic Kidney Laceration. PMID- 26279512 TI - A Young Man with Abdominal Trauma and Inability to Void. PMID- 26279513 TI - Falcine and Tentorial Subdural Hematomas May Not Routinely Require Transfer to a Tertiary Care Center. AB - BACKGROUND: Patients with subdural hematomas (SDH) are frequently transferred to tertiary care centers. Although many prognostic factors, treatment strategies, and outcomes for convexity SDH have been reported, little is known about falcine and tentorial SDH. OBJECTIVES: To describe features and outcomes of isolated falcine and tentorial SDH. METHODS: We reviewed clinical/radiographic findings, treatment, length of stay (LOS), and outcome of adult patients transferred to a tertiary care center for acute SDH. Characteristics of patients with isolated falcine/tentorial SDH and outcomes (favorable [discharge to home/acute rehabilitation] vs. unfavorable [death/hospice/skilled nursing facility/long term care]) were assessed with univariate analyses. RESULTS: Of 210 patients with SDH, mean age was 69.5 years; 117 were male; 98 (47%) underwent surgical SDH evacuation. Twenty-seven patients had isolated falcine or tentorial SDH, with known traumatic etiology in 23. None of the falcine/tentorial SDH patients required surgery or intubation. Compared with convexity SDH, patients with falcine/tentorial SDH were younger (59.7 vs. 70.9 years, p = 0.01), had higher admission Glasgow Coma Scale scores at the referring (p = 0.01) and receiving facility (p = 0.004), and shorter median intensive care unit LOS (1 vs. 3, p < 0.0001). All patients (100%) with falcine/tentorial SDH had favorable outcome vs. 68% with convexity SDH (p = 0.0005). CONCLUSION: Isolated tentorial/falcine SDH without associated neurological deficits represent a benign entity among acute SDH, with no need for surgical intervention, short LOS, and favorable outcome. Our data indicate that for these patients, in the absence of complicating factors, transfer to a tertiary care center may not be routinely indicated. PMID- 26279514 TI - Emergency Department Crowding in Relation to In-hospital Adverse Medical Events: A Large Prospective Observational Cohort Study. AB - BACKGROUND: Emergency department (ED) crowding has been linked with adverse medical events. However, this association was inadequately controlled for potential confounding variables. OBJECTIVES: To investigate whether ED crowding is independently associated with risk of in-hospital death and morbidity, and longer total hospital stay. METHODS: Prospective observational cohort study of all patients (>= 18 years) presenting to the ED of an academic teaching hospital in Leuven, Belgium from June 21, 2010 to July 20, 2012. Multivariate logistic regression and proportional hazard analysis was used to control for risk factors. ED occupancy was determined for 108,229 included patients and labeled "ED crowding" when occupancy was within the highest quartile of occupancy. Outcomes within 10 days of ED admission included in-hospital death, hospital-acquired morbidities, and total hospital stay. RESULTS: During ED crowding, a median of 58 (interquartile range 55-63) patients were present for 40 licensed treatment bays. After controlling for all baseline risk factors and as compared with the lowest quartile of ED occupancy (30 [26-32] patients), ED crowding was not independently associated with mortality (odds ratio [OR] 0.94, 95% confidence interval [CI] 0.74-1.19; p = 0.6), but tended to be associated with higher incidence of hospital-acquired pneumonia (OR 1.24, 95% CI 0.96-1.62; p = 0.09). CONCLUSIONS: Failing to control for baseline risk factors may have led to false-positive associations between ED crowding and mortality in previous studies. After controlling for risk factors, we showed that ED crowding was associated with longer hospital stays but not with increased mortality. PMID- 26279516 TI - Meta-analysis of congenitally missing teeth in the permanent dentition: Prevalence, variations across ethnicities, regions and time. AB - BACKGROUND: Congenitally missing teeth (CMT) are of concern to many fields of dentistry. Only a few reviews have been published in this regard. AIM: The aim was to analyze the literature on CMT in the permanent dentition, excluding the third molars, and to identify potential links with ethnicity, geographical regions, and time. METHODS: A total of 118 reports on CMT were collected by two authors by interrogating databases. Sample homogeneity, publication bias, publication year (in Caucasian and Mongoloid samples, and in general), ethnicities, and geography of CMT prevalence were statistically analyzed using a Q-test, Egger regression, linear regression, a Spearman coefficient, Kruskal Wallis, a Dunn post-hoc (alpha = 0.05), and a Mann-Whitney U test (alpha = 0.0125, alpha = 0.0071). RESULTS: The mean CMT prevalence was 6.53% +/- 3.33%. There were significant geographic differences in CMT rates (P = 0.0001, Kruskal Wallis) and between ethnicities (P = 0.0002, Kruskal-Wallis). According to the Mann-Whitney U test (alpha = 0.0071), eastern Asians (P = 0.0008) and Europeans (marginally significant, P = 0.0128) showed an elevated prevalence, while Western Asians (P = 0.0001) and Americans (marginally significant, P = 0.0292) had lower prevalence rates. Compared with other ethnicities, Mongoloids showed higher prevalence (P = 0.0009) while Asian Caucasians showed lower rates (P = 0.0005, Mann-Whitney U, alpha = 0.0125). The year of publication was not significantly correlated with any of the subsamples studied (P > 0.3, linear regression). CONCLUSIONS: Clinicians should be vigilant in the assessment of CMT in Mongoloids. No increase of this condition was detected during the last century. PMID- 26279517 TI - European College of Orthodontics: Commission of Affiliation and Titularisation. AB - Date of birth: 15 April 1999; sex: female. A. PRETREATMENT RECORDS: 11 years 6 months; 10/2010. DIAGNOSIS: Angle Class I; Tooth-arch discrepancy; Teeth missing prior to treatment: none. TREATMENT PLAN: Correction of the tooth-arch discrepancy by extraction of 14, 24, 34, and 44; Appliances and devices: Bimaxillary vestibular multibracket appliances; Start of treatment: 11 years 6 months; 10/2010. B. POST-TREATMENT RECORDS: 1/2013; 13 years 9 months. DURATION OF ACTIVE TREATMENT: 27 months. RETENTION: Maxillary: Hawley retainer worn at night; Mandibular: bonded wire from 35 to 45. C. POST-RETENTION RECORDS: (1 year minimum): 2/2014; 14 years 10 months. PMID- 26279519 TI - An economy of scales: A selective review of obesity's economic causes, consequences, and solutions. AB - This paper reviews the economic research on obesity, covering topics such as the measurement of, and trends in, obesity, the economic causes of obesity (e.g. the monetary price and time cost of food, food assistance programs, income, education, macroeconomic conditions, and peer effects), and the economic consequences of obesity (e.g. lower wages, a lower probability of employment, and higher medical care costs). It also examines the extent to which obesity imposes negative externalities, and economic interventions that could potentially internalize such externalities, such as food taxes, subsidies for school-based physical activity programs, and financial rewards for weight loss. It discusses other economic rationales for government intervention with respect to obesity, such as imperfect information, time inconsistent preferences, and irrational behavior. It concludes by proposing a research agenda for the field. Overall, the evidence suggests that there is no single dominant economic cause of obesity; a wide variety of factors may contribute a modest amount to the risk. There is consistent evidence regarding the economic consequences of obesity, which are lower wages and higher medical care costs that impose negative externalities through health insurance. Studies of economic approaches to preventing obesity, such as menu labeling, taxes on energy-dense foods, and financial rewards for weight loss find only modest effects on weight and thus a range of policies may be necessary to have a substantial effect on the prevalence of obesity. PMID- 26279520 TI - Post-transplant lymphoproliferative disorders: from epidemiology to pathogenesis driven treatment. AB - Post-transplant lymphoproliferative disorders (PTLDs) represent the most severe complication of both solid organ and hematopoietic stem cell transplantation. The Epstein-Barr Virus (EBV) is the main driver of PTLD, particularly those occurring early after transplantation. EBV-driven malignancies are associated with selective expression of latent viral proteins, but uncontrolled lytic replication may favor early phases of cell transformation. Besides immunodepression, persistent immune activation and chronic inflammation play an important role in both virus reactivation and expansion of EBV-infected B cells. EBV-induced immortalization requires the expression of telomerase. TERT, the rate-limiting component of the telomerase complex, is central in the switch from the lytic to the latent viral program, and TERT inhibition induces the EBV lytic cycle and cell death. Immunotherapy and combination of EBV lytic cycle inducers with antiviral drugs are promising strategies to improve the treatment of PTLD patients. This review is aimed at providing an update on the intriguing association between EBV and PTLD, mainly focusing on cases arising after kidney and liver transplantation, which account for the vast majority of transplants. PMID- 26279521 TI - The molecular signature of AML mesenchymal stromal cells reveals candidate genes related to the leukemogenic process. AB - Acute myeloid leukemia (AML) is a heterogeneous disease characterized by myeloid precursor proliferation in the bone marrow, apoptosis reduction and differentiation arrest. Although there are several studies in this field, events related to disease initiation and progression remain unknown. The malignant transformation of hematopoietic stem cells (HSC) is thought to generate leukemic stem cells, and this transformation could be related to changes in mesenchymal stromal cell (hMSC) signaling. Thus, the aim of this work was to analyze the gene expression profile of hMSC from AML patients (hMSC-AML) compared to healthy donors hMSCs (hMSC-HD). The results showed a common molecular signature for all hMSC-AML. Other assays were performed with a large number of patients and the results confirmed a molecular signature that is capable of distinguishing hMSC AML from hMSC-HD. Moreover, CCL2 and BMP4 genes encode secreted proteins that could affect HSCs. To verify whether these proteins are differentially expressed in AML patients, ELISA was performed with plasma samples. CCL2 and BMP4 proteins are differentially expressed in AML patients, indicating changes in hMSC-AML signaling. Altogether, hMSCs-AML signaling alterations could be an important factor in the leukemic transformation process. PMID- 26279522 TI - The influence of the hexopyranose ring geometry on the conformation of glycosidic linkages investigated using molecular dynamics simulations. AB - The conformation of the carbohydrate molecules is a subject of many theoretical and experimental studies. The different timescales associated with the particular degrees of freedom hinder the progress in both those fields. The present paper reports the results of computational studies aimed at elucidating and characterizing the potential correlations between the two main structural determinants of the carbohydrate structure, i.e. the ring conformation and the orientation of the glycosidic bonds (expressed in terms of the phi and psi glycosidic dihedral angles). The free energy landscapes computed for 16 different oligomers composed of unsubstituted, 1,4-linked hexopyranose residues allowed for a detailed insight into how the ring geometry affects the glycosidic linkage conformation. The factor of main importance appeared to be the local changes of the chain length induced by the ring conformational rearrangements. This effect is important mainly for the carbohydrate chains exploiting the glycosidic bonds of uniform orientation with respect to the ring (i.e. either exclusively axially or exclusively equatorially oriented). The shape of the ring may affect the (phi,psi) free energy maps but only if the population of the alternative ring conformers is relatively high and (at the same time) the presence of such conformers is associated with the significant shifts of the favorable phi and psi values. PMID- 26279523 TI - Ferrier reaction in a deep eutectic solvent. AB - A mild and efficient synthesis of 2,3-unsaturated sugar derivatives has been achieved by conducting the Ferrier reaction in a deep eutectic solvent (DES). A wide range of alcohols including primary, secondary, benzylic, and sugar-derived primary alcohols can be used. Advantages include good yields, shorter reaction times and recyclability of DES. PMID- 26279524 TI - Identification, biochemical characterization, and in-vivo expression of the intracellular invertase BfrA from the pathogenic parasite Leishmania major. AB - The parasitic life cycle of Leishmania includes an extracellular promastigote stage that occurs in the gut of the insect vector. During that period, the sucrose metabolism and more specifically the first glycosidase of this pathway are essential for growth and survival of the parasite. We investigated the expression of the invertase BfrA in the promastigote and amastigote stages of three parasite species representative of the three various clinical forms and of various geographical areas, namely Leishmania major, L. donovani and L. braziliensis. Thereafter, we cloned, overexpressed and biochemically characterized this invertase BfrA from L. major, heterologously expressed in both Escherichia coli and L. tarentolae. For all species, expression levels of BfrA mRNA were correlated to the time of the culture and the parasitic stage (promastigotes > amastigotes). BfrA exhibited no activity when expressed as a glycoprotein in L. tarentolae but proved to be an invertase when not glycosylated, yet owing low sequence homology with other invertases from the same family. Our data suggest that BfrA is an original invertase that is located inside the parasite. It is expressed in both parasitic stages, though to a higher extent in promastigotes. This work provides new insight into the parasite sucrose metabolism. PMID- 26279525 TI - S-Ribosylhomocysteine analogs containing a [4-thio]ribose ring. AB - The [4-thio]-S-ribosylhomocysteine (SRH) analogs containing substitution of a sulfur atom for the endocyclic oxygen were synthesized by coupling of the 4 thioribose substrates with a thiolate generated from the protected homocysteine. Coupling of the protected 1-deoxy-5-O-mesyl-S-oxo-4-thio-D-ribofuranose with homocysteinate salt gave the C4 epimers of [4-thio]-SRH at the sulfoxide oxidation level lacking a hydroxyl group at anomeric carbon. Treatment of these sulfoxides with BF3?Et2O/NaI affected simultaneous reduction to sulfide and global deprotection affording 1-deoxy-4-thio-SRH analog. Treatment of the protected 1-deoxy-S-oxo-4-thio-D-ribofuranose sulfoxide with DAST/SbCl3 resulted in the fluoro-Pummerer rearrangement to give 4-thio-beta-D-ribofuranosyl fluoride. Mesylation of the latter at 5-hydroxyl position followed by coupling with homocysteinate salt and subsequent global deprotection with trifluoroacetic acid afforded [4-thio]-SRH thiohemiacetal. PMID- 26279526 TI - Comparison of polysaccharides of Haliotis discus hannai and Volutharpa ampullacea perryi by PMP-HPLC-MS(n) analysis upon acid hydrolysis. AB - Haliotis discus hannai Ino (Haliotis) is a highly valued marine shellfish, and it is sometimes replaced by another cheaper Gastropoda mollusk, Volutharpa ampullacea perryi (Volutharpa). Polysaccharides from pleopods, viscera and gonads of these two gastropods were compared by analyzing the mono- and di-saccharides in their acid hydrolysates using high performance liquid chromatography-mass spectrometry (HPLC-MS(n)) after 1-phenyl-3-methyl-5-pyrazolone (PMP) derivatization. Disaccharide analysis revealed the distribution of uronic acid containing polysaccharides (UACPs) in the biological samples. GlcA-(1 -> 2)-Man, GlcA-(1 -> 3)-GalN, and another disaccharide consisting of a hexuronic acid linked to a hexose were found in the hydrolysates, which indicated the existence of AGSP (abalone gonad sulfated polysaccharide) with the backbone composed of -> 2)-alpha-Man(1 -> 4)-beta-GlcA(1 -> repeating unit, AAP (abalone glycosaminoglycan-like polysaccharide) with the backbone of -> 3)-GalNAc-(1 -> 2) GlcA-(1 -> 3)-GalNAc-(1 -> 4)-GlcA-(1 -> repeating unit, and unidentified DS1P containing a hexuronic acid linked to a hexose unit, respectively. As shown by extracted ion chromatograms (XICs), AAP was the only UACP found in pleopods of the two gastropods; gonads and viscera of Haliotis contained DS1P and AGSP, while those of Volutharpa contained DS1P, AGSP as well as AAP. Monosaccharides in the acid hydrolysates were demonstrated in XICs by extracting their corresponding PMP derivative quasi-molecular ions one by one, and the results indicated the similar conclusion to the disaccharide analysis. Therefore, it could be concluded that polysaccharides from pleopods of the two gastropods are very similar, while those from their viscera and gonads differ greatly. PMID- 26279527 TI - Pilot use of a novel smartphone application to track traveller health behaviour and collect infectious disease data during a mass gathering: Hajj pilgrimage 2014. AB - This study examines the feasibility of using a smartphone application (app) to conduct surveys among travellers during the Hajj pilgrimage, where the use of apps has not been evaluated for infectious disease surveillance. A longitudinal study was conducted among pilgrims at the Hajj 2014 using an iPhone app with separate questionnaires for three study phases covering before, during, and after Hajj. Forty-eight pilgrims from 13 countries downloaded the app. Respondents were aged between 21 and 61 (median 36) years and 58.5% (24/41) were male. Of these, 85% (41/48) completed the first phase, 52% (25/41) completed both the second and third phases, and 25 of these reported meningococcal vaccination, with 36% (9/25) receiving other vaccines. All (25) reported hand hygiene use and 64% (16/25) wore a facemask at some point during the pilgrimage. Four (6%) reported close contact with camels. Respiratory symptoms commenced from the 4th day of Hajj, with sore throat (20%) and cough (12%) being the most common. Three participants (12%) reported respiratory symptoms after returning home. Conducting a prospective survey using a smartphone app to collect data on travel-associated infections and traveller compliance to prevention is feasible at mass gatherings and can provide useful data associated with health-related behaviour. PMID- 26279528 TI - A novel technique for spreader graft placement without dorsum resection during septoplasty. AB - OBJECTIVE: This paper presents a novel method for spreader graft placement without dorsum resection in patients who have a deviated septum with a narrow internal nasal valve angle. METHODS: A Killian incision was used for the endonasal septoplasty, and all spreader grafts were harvested from excised deviated septal cartilages. Procedures were conducted under general anaesthesia at the same centre by the same surgical team that performed the endonasal procedure. Successful placement of spreader grafts was achieved endonasally. CONCLUSION: Although the endonasal placement of spreader grafts seems to be more difficult than placement conducted by an open approach technique, an endonasal procedure has many advantages. Our technique provides surgeons with the opportunity to shorten operation time, obtain autologous septal graft material and secure the columellar architecture. Surgeons familiar with the classical (endonasal) septoplasty procedure can easily apply this technique to widen a narrow internal nasal valve angle, without corrupting nasal integrity. PMID- 26279529 TI - Structure-Photoluminescence Correlation for Two Crystalline Polymorphs of a Thiophene-Phenylene Co-Oligomer with Bulky Terminal Substituents. AB - Two crystal polymorphs of a thiophene-phenylene hexamer with bulky terminal substituents are characterized by different molecular conformations and parallel versus herringbone packing. Irrespective of their similar emissive spectra and common H-aggregate features, evidenced by crystal structure analysis and confirmed by solid-phase and excited-state first-principles calculations, their luminescence is relatively high and, for one form, nearly double than that for the other. Interaromatic packing energy contributions are established by quantum chemical calculations and can be compared quantitatively as the same species in different crystal environments is examined. The different luminescence efficiency of the two phases highlights the crucial role of the interaromatic packing for the luminescence properties of polyaromatic oligomers. PMID- 26279530 TI - Terahertz Dynamics in Human Cells and Their Chromatin. AB - The terahertz dynamics of human cells of the U937 line and their chromatin has been investigated by high-resolution inelastic X-ray scattering. To highlight its dynamical features in situ, nuclear DNA has been stained by uranyl-acetate salt. The general behavior of the collective dynamics of the whole cell is quite similar to that of bulk water, with a nearly wavevector-independent branch located at about 5 meV and a propagating mode with a linear trend corresponding to a speed of sound of 2900 +/- 100 m/s. We provide the first experimental evidence for the existence of two branches also in the dispersion curves of chromatin. The high-energy mode displays an acoustic-like behavior with a sound velocity similar to unstained cells, but in this case the branch likely originates from the superposition of intramolecular DNA optic modes. A low-energy optic-like branch, distinctive of the chromatin moiety, is found at about 2.5 meV. PMID- 26279531 TI - Unwinding Au(+)...Au(+) Bonded Filaments in Ligand-Supported Gold(I) Polymer under Pressure. AB - The ultimately thin single-strand gold filaments, of Au(+)...Au(+) bonded gold(I) diethyldithiocarbamate polymer, AuEt2DTC, can be transformed depending on pressure and solvate contents. When synthesized in the presence of CH2Cl2, it crystallizes into a tetragonal AuEt2DTC.xCH2Cl2 phase alpha with ligand-supported and unsupported Au(+)...Au(+) bonded filaments modulated into molecular Au8-pitch helices. Low contents of CH2Cl2 favors the beta phase of significantly reduced volume and orthorhombic space group Fddd. The alpha-AuEt2DTC.xCH2Cl2 crystal exhibits a highly unusual negative-area compressibility, due to the spring-like compression of helices. Above 0.05 GPa, the crystal transforms to phase beta, where the Au16-pitch helices partly unwind their turns, which relaxes the tension generated by external pressure between neighboring helices of the opposite handedness. This is a unique observation of atomic-scale helical filaments transformation, which otherwise is a universal process analogous to the helix reversal between DNA forms B and Z, and in macroscopic world it is similar to nonperiodic unwind kinks in grapevine tendrils and telephone cords. Pressure also reduces the differences between the ligand-supported and unsupported Au(+)...Au(+) bonds. PMID- 26279532 TI - Thermally Activated Exciton Dissociation and Recombination Control the Carrier Dynamics in Organometal Halide Perovskite. AB - Solar cells based on organometal halide perovskites have seen rapidly increasing efficiencies, now exceeding 15%. Despite this progress, there is still limited knowledge on the fundamental photophysics. Here we use microwave photoconductance and photoluminescence measurements to investigate the temperature dependence of the carrier generation, mobility, and recombination in (CH3NH3)PbI3. At temperatures maintaining the tetragonal crystal phase of the perovskite, we find an exciton binding energy of about 32 meV, leading to a temperature-dependent yield of highly mobile (6.2 cm(2)/(V s) at 300 K) charge carriers. At higher laser intensities, second-order recombination with a rate constant of gamma = 13 * 10(-10) cm(3) s(-1) becomes apparent. Reducing the temperature results in increasing charge carrier mobilities following a T(-1.6) dependence, which we attribute to a reduction in phonon scattering (SigmaMU = 16 cm(2)/(V s) at 165 K). Despite the fact that SigmaMU increases, gamma diminishes with a factor six, implying that charge recombination in (CH3NH3)PbI3 is temperature activated. The results underline the importance of the perovskite crystal structure, the exciton binding energy, and the activation energy for recombination as key factors in optimizing new perovskite materials. PMID- 26279533 TI - Kinetic Charging Inversion in Ionic Liquid Electric Double Layers. AB - The charging kinetics of electric double layers (EDLs) has a pivotal role in the performance of a wide variety of nanostructured devices. Despite the prevalent use of ionic liquids as the electrolyte, relatively little is known on the charging behavior from a microscopic perspective. Here, we study the charging kinetics of ionic liquid EDLs using a classical time-dependent density functional theory that captures the molecular excluded volume effects and electrostatic correlations. By examining variations of the ionic density profiles and the charging density in response to an electrode voltage, we find that at certain conditions, the electrode charge shows a rapid surge in its initial response, rises quickly to the maximum, and then slowly decays toward equilibrium. The electrode charge and voltage may have opposite signs when the cell width is commensurate with the layer-by-layer ionic distributions. This unusual charging behavior can be explained in terms of the oscillatory structure of ionic liquids near the electrodes. PMID- 26279534 TI - Chirped-Pulse Fourier Transform Microwave Spectroscopy Coupled with a Flash Pyrolysis Microreactor: Structural Determination of the Reactive Intermediate Cyclopentadienone. AB - Chirped-pulse Fourier transform microwave spectroscopy (CP-FTMW) is combined with a flash pyrolysis (hyperthermal) microreactor as a novel method to investigate the molecular structure of cyclopentadienone (C5H4?O), a key reactive intermediate in biomass decomposition and aromatic oxidation. Samples of C5H4?O were generated cleanly from the pyrolysis of o-phenylene sulfite and cooled in a supersonic expansion. The (13)C isotopic species were observed in natural abundance in both C5H4?O and in C5D4?O samples, allowing precise measurement of the heavy atom positions in C5H4?O. The eight isotopomers include: C5H4?O, C5D4?O, and the singly (13)C isotopomers with (13)C substitution at the C1, C2, and C3 positions. Microwave spectra were interpreted by CCSD(T) ab initio electronic structure calculations and an re molecular structure for C5H4?O was found. Comparisons of the structure of this "anti-aromatic" molecule are made with those of comparable organic molecules, and it is concluded that the disfavoring of the "anti-aromatic" zwitterionic resonance structure is consistent with a more pronounced C?C/C-C bond alternation. PMID- 26279535 TI - Rainbow Emission from an Atomic Transition in Doped Quantum Dots. AB - Although semiconductor quantum dots are promising materials for displays and lighting due to their tunable emissions, these materials also suffer from the serious disadvantage of self-absorption of emitted light. The reabsorption of emitted light is a serious loss mechanism in practical situations because most phosphors exhibit subunity quantum yields. Manganese-based phosphors that also exhibit high stability and quantum efficiency do not suffer from this problem but in turn lack emission tunability, seriously affecting their practical utility. Here, we present a class of manganese-doped quantum dot materials, where strain is used to tune the wavelength of the dopant emission, extending the otherwise limited emission tunability over the yellow-orange range for manganese ions to almost the entire visible spectrum covering all colors from blue to red. These new materials thus combine the advantages of both quantum dots and conventional doped phosphors, thereby opening new possibilities for a wide range of applications in the future. PMID- 26279536 TI - Ultralow Threshold One-Photon- and Two-Photon-Pumped Optical Gain Media of Blue Emitting Colloidal Quantum Dot Films. AB - Colloidal quantum dots (QDs) offer advantageous properties as an optical gain media for lasers. Optical gain in the QDs has been shown in the whole visible spectrum, yet it has been intrinsically challenging to realize efficient amplified spontaneous emission (ASE) and lasing in the blue region of the visible spectrum. Here, we synthesize large-sized core/gradient shell CdZnS/ZnS QDs as an efficient optical gain media in the blue spectral range. In this Letter, we demonstrate for the first time that two-photon-absorption-pumped ASE from the blue-emitting QD is achievable with a threshold as low as 6 mJ/cm(2). Utilizing these QDs, we also report one-photon-absorption-pumped ASE at an ultralow threshold of ~60 MUJ/cm(2), which is comparable to the state-of-the-art red emitting QD-based gain media. This one-photon-pumped ASE threshold is an order of magnitude better than that of the previously reported best blue-emitting QD-based gain media. PMID- 26279537 TI - Direct Evidence for Transient Pair Formation between a Solvated Electron and H3O(+) Observed by Picosecond Pulse Radiolysis. AB - The reaction between the solvated electron and hydronium cation H3O(+) in water constitutes a fundamental reaction in chemistry. Due to significant rearrangement of solvent molecules around both the electron and H3O(+), the reaction rate of this process is not controlled by diffusion. The presence of a reaction barrier suggests the formation of an intermediate that has so far not been observed. Here, the time-resolved visible absorption spectra in three concentrated acid solutions, perchloric, sulfuric, and phosphoric, at various concentrations are recorded by the picosecond pulse radiolysis method. In contrast to previous reports, a strong blue shift of the absorption band of the solvated electron in acidic solutions compared to neat water is clearly observed, consistent with formation of a pair between the solvated electron and hydronium cation. PMID- 26279538 TI - Direct Determination of the Simplest Criegee Intermediate (CH2OO) Self Reaction Rate. AB - The rate of self-reaction of the simplest Criegee intermediate, CH2OO, is of importance in many current laboratory experiments where CH2OO concentrations are high, such as flash photolysis and alkene ozonolysis. Using laser flash photolysis while simultaneously probing both CH2OO and I atom by direct absorption, we can accurately determine absolute CH2OO concentrations as well as the UV absorption cross section of CH2OO at our probe wavelength (lambda = 375 nm), which is in agreement with a recently published value. Knowing absolute concentrations we can accurately measure kself = 6.0 +/- 2.1 * 10(-11)cm(3) molecule(-1) s(-1) at 297 K. We are also able to put an upper bound on the rate coefficient for CH2OO + I of 1.0 * 10(-11) cm(3) molecule(-1) s(-1). Both of these rate coefficients are at least a factor of 5 smaller than other recent measurements of the same reactions. PMID- 26279539 TI - Are Hot Spots between Two Plasmonic Nanocubes of Silver or Gold Formed between Adjacent Corners or Adjacent Facets? A DDA Examination. AB - Of all the plasmonic solid nanoparticles, single Ag or Au nanocubes are known to be plasmonic nanoparticles with strong plasmonic fields, which are concentrated around their corners. However, when nanoparticles aggregate, they do so in a face to face arrangement. The formation of hot spots between plasmonic nanoparticles in close proximity to each other is known to greatly enhance their plasmonic fields which are important in the field of imaging. Thus, what is the structural development of hot spots between two nanocubes in a dimer? Do they form between the corners or are they between the adjacent facets, and what does this depend on? A detailed discrete dipole approximation (DDA) simulation of Au-Au and Ag-Ag dimers suggests that there is a competition between their formation in these two locations, which depends on the polarization direction of the exciting light (with respect to the interparticle axis in the dimer), its intensity and the wavelength as well as the interparticle separation of the dimer. PMID- 26279540 TI - Aqueous Cation-Amide Binding: Free Energies and IR Spectral Signatures by Ab Initio Molecular Dynamics. AB - Understanding specific ion effects on proteins remains a considerable challenge. N-methylacetamide serves as a useful proxy for the protein backbone that can be well characterized both experimentally and theoretically. The spectroscopic signatures in the amide I band reflecting the strength of the interaction of alkali cations and alkaline earth dications with the carbonyl group remain difficult to assign and controversial to interpret. Herein, we directly compute the infrared (IR) shifts corresponding to the binding of either sodium or calcium to aqueous N-methylacetamide using ab initio molecular dynamics simulations. We show that the two cations interact with aqueous N-methylacetamide with different affinities and in different geometries. Because sodium exhibits a weak interaction with the carbonyl group, the resulting amide I band is similar to an unperturbed carbonyl group undergoing aqueous solvation. In contrast, the stronger calcium binding results in a clear IR shift with respect to N methylacetamide in pure water. PMID- 26279541 TI - Mid-Infrared Time-Resolved Frequency Comb Spectroscopy of Transient Free Radicals. AB - We demonstrate time-resolved frequency comb spectroscopy (TRFCS), a new broadband absorption spectroscopy technique for the study of trace free radicals on the microsecond timescale. We apply TRFCS to study the time-resolved, mid-infrared absorption of the deuterated hydroxyformyl radical trans-DOCO, an important short lived intermediate along the OD + CO reaction path. Directly after photolysis of the chemical precursor acrylic acid-d1, we measure absolute trans-DOCO product concentrations with a sensitivity of 5 * 10(10) cm(-3) and observe its subsequent loss with a time resolution of 25 MUs. The multiplexed nature of TRFCS allows us to detect simultaneously the time-dependent concentration of several other photoproducts and thus unravel primary and secondary chemical reaction pathways. PMID- 26279542 TI - Effects of Zero-Point Delocalization on the Vibrational Frequencies of Mixed HCl and Water Clusters. AB - We demonstrate the significant effect that large-amplitude zero-point vibrational motion can have on the high-frequency fundamental vibrations of molecular clusters, specifically small (HCl)n-(H2O)m clusters. Calculations were conducted on a many-body potential, constructed from a mix of new and previously reported semiempirical and high-level ab initio potentials. Diffusion Monte Carlo simulations were performed to determine ground-state wave functions. Visualization of these wave functions indicates that the clusters exhibit delocalized ground states spanning multiple stationary point geometries. The ground states are best characterized by planar ring configurations, despite the clusters taking nonplanar configurations at their global minima. Vibrational calculations were performed at the global minima and the Diffusion Monte Carlo predicted configurations and also using an approach that spans multiple stationary points along a rectilinear normal-mode reaction path. Significantly better agreement was observed between the calculated vibrational frequencies and experimental peak positions when the delocalized ground state was accounted for. PMID- 26279543 TI - Long-Lived Charge Separated State in NiO-Based p-Type Dye-Sensitized Solar Cells with Simple Cyclometalated Iridium Complexes. AB - Three new cyclometalated iridium complexes were prepared and investigated on nanocrystalline NiO cathodes. Nanosecond transient absorption spectroscopy experiments show they present a surprisingly slow geminate charge recombination upon excitation on NiO, representing thus the first examples of simple sensitizers with such feature. These complexes were used in dye-sensitized solar cells using nanocrystalline NiO film as semiconductor. The long-lived charge separated state of these Ir complexes make them compatible with other redox mediators than I3(-)/I(-), such as a cobalt electrolyte and enable to reach significantly high open circuit voltage. PMID- 26279544 TI - Explicit Differentiation of G-Quadruplex/Ligand Interactions: Triplet Excited States as Sensitive Reporters. AB - We report a new transient spectral method utilizing triplet excited state as sensitive reporters to monitor and differentiate the multiplex G quadruplex/ligand interactions in a single assay, which is a difficult task and usually requires a combination of several techniques. From a systematic study on the interactions of porphyrin (TMPyP4) with each telomeric G-quadruplex: AG3(T2AG3)3, G2T2G2TGTG2T2G2, (G4T4G4)2, and (TG4T)4, it is convincingly shown that the ligand triplet decay lifetimes are sensitive to the local bound microenvironment within G-quadruplexes, from which the coexisting binding modes of end-stacking, intercalation, and sandwich are distinguished and their respective contribution are determined. The complete scenario of mixed interaction modes is thus revealed, shedding light on the past controversial issues. Additional control experiments demonstrate the sensitivity of this triplet reporter method, which can even capture the binding behavior change as the G-quadruplex structures are adjusted by Na(+) or K(+). PMID- 26279545 TI - Theoretical Prediction of Isotope Effects on Charge Transport in Organic Semiconductors. AB - We suggest that the nuclear tunneling effect is important in organic semiconductors, which we showed is absent in both the widely employed Marcus theory and the band-like transport as described by the deformation potential theory. Because the quantum nuclear tunneling tends to favor electron transfer while heavier nuclei decrease the quantum effect, there should occur an isotope effect for carrier mobility. For N,N'-n-bis(n-hexyl)-naphthalene diimide, electron mobility of all-deuteration on alkyls and all (13)C-substitution on the backbone decrease ~18 and 7%, respectively. Similar isotope effects are found in the N,N'-n-bis(n-octyl)-perylene diimide. However, there is nearly no isotope effect for all-deuterated rubrene or tetracene. We have found that the isotopic effect only occurs when the substituted nuclei contribute actively to vibrations with appreciable charge reorganization energy and coupling with carrier motion. Thus, this prediction can shed light on the current dispute over the hopping versus band-like mechanisms in organic semiconductors. PMID- 26279546 TI - Direct Measurement of Energy Migration in Supramolecular Carbocyanine Dye Nanotubes. AB - Exciton transport lengths in double-walled and bundled cylindrical 3,3'-bis- (2 sulfopropyl)-5,5',6,6'-tetrachloro-1,1'-dioctylbenzimida-carbocyanine (C8S3) J aggregates were measured using direct imaging of fluorescence from individual aggregates deposited on solid substrates. Regions identified in confocal images were excited with a focused laser spot, and the resulting fluorescence emission was imaged onto an electron multiplying charged coupled device camera. A two dimensional Gaussian fitting scheme was used to quantitatively compare the excitation beam profile to the broadened aggregate emission profiles. The double walled tubes exhibit average exciton transport lengths of 140 nm, while exciton transport in the bundled nanotubes was found to be remarkably long, with distances reaching many hundreds of nanometers. A steady-state one-dimensional diffusion model for the broadening of the emission profiles yields diffusion coefficients of 120 nm(2) ps(-1) for the nanotubes and 7000 nm(2) ps(-1) for the aggregate bundles. The level of structural hierarchy dramatically affects the exciton transport capabilities in these artificial light-harvesting systems, and energy migration is not limited to a single dimension in J-aggregate bundles. PMID- 26279547 TI - How to Draw Energy Level Diagrams in Excitonic Solar Cells. AB - Emerging photovoltaic devices based on molecular and nanomaterials are mostly excitonic in nature. The initial absorption of a photon in these materials creates an exciton that can subsequently dissociate in each material or at their interfaces to give charge carriers. Any attempt at mechanistic understanding of excitonic solar cells must start with drawing energy level diagrams. This seemingly elementary exercise, which is described in textbooks for inorganic solar cells, has turned out to be a difficult subject in the literature. The problem stems from conceptual confusion of single-particle energy with quasi particle energy and the misleading practice of mixing the two on the same energy level diagram. Here, I discuss how to draw physically accurate energy diagrams in excitonic solar cells using only single-particle energies (ionization potentials and electron affinities) of both ground and optically excited states. I will briefly discuss current understanding on the electronic energy landscape responsible for efficient charge separation in excitonic solar cells. PMID- 26279548 TI - Toward a Quantitative Understanding of the Electric Field in Thermal Metal Oxidation and a Self-Consistent Wagner Theory. AB - The electric field in the growing oxide film is important to the kinetics and mechanism of metal oxidation. However, understanding of the essential characteristics of the electric field during oxidation remains insufficient. A special-case analytical model is presented that provides a unified understanding for the electric field from the viewpoints of kinetics and thermodynamics. More general cases are studied by computer simulations that show similar characteristics in the electric field. In particular, simulations indicate that in many situations, the electrostatic potential drop across the bulk oxide is limited to ~kBT/e, which means that the total electrostatic potential drop across the oxide film, if on the order of 1 V by rough estimation, should have contributions mostly from the electrified interfaces. Finally, regarding the Gibbs-Duhem relation, the commonly used isobaric assumption for the diffusing species is refuted. The results contained herein also provide a self-consistent understanding of Wagner's oxidation theory. PMID- 26279549 TI - Effect of Ag(+) on the Excited-State Properties of a Gas-Phase (Cytosine)2Ag(+) Complex: Electronic Transition and Estimated Lifetime. AB - Recently, DNA molecules have received great attention because of their potential applications in material science. One interesting example is the production of highly fluorescent and tunable DNA-Agn clusters with cytosine (C)-rich DNA strands. Here, we report the UV photofragmentation spectra of gas-phase cytosine...Ag(+)...cytosine (C2Ag(+)) and cytosine...H(+)...cytosine (C2H(+)) complexes together with theoretical calculations. In both cases, the excitation energy does not differ significantly from that of isolated cytosine or protonated cytosine, indicating that the excitation takes place on the DNA base. However, the excited-state lifetime of the C2H(+) (tau = 85 fs), estimated from the bandwidth of the spectrum, is at least 2 orders of magnitude shorter than that of the C2Ag(+) (tau > 5000 fs). The increased excited-state lifetime upon silver complexation is quite unexpected, and it clearly opens the question about what factors are controlling the nonradiative decay in pyrimidine DNA bases. This is an important result for the expanding field of metal-mediated base pairing and may also be important to the photophysical properties of DNA-templated fluorescent silver clusters. PMID- 26279550 TI - Radical Ions of Cycloparaphenylenes: Size Dependence Contrary to the Neutral Molecules. AB - Cycloparaphenylenes (CPPs) have attracted wide attention because of their interesting properties owing to distorted and strained aromatic systems and radially oriented p orbitals. For application of CPPs, information on their charged states (radical cation and radical anion) is essential. Here, we measured absorption spectra of the radical cations and the radical anions of CPPs with various ring sizes over a wide spectral region by means of radiation chemical methods. The peak position of the near-IR bands for both the radical cation and the radical anion shifted to lower energies with an increase in the ring size. This trend is contrary to what is observed for transitions between the HOMO and LUMO of the neutral CPP. The observed spectra of the CPP radical ions were reasonably assigned based on time-dependent density functional theory. These results indicate that the next HOMO and the next LUMO levels are important in the electronic transitions of radical ions. PMID- 26279551 TI - Multifunctional Sn- and Fe-Codoped In2O3 Colloidal Nanocrystals: Plasmonics and Magnetism. AB - We prepared Fe- and Sn-codoped colloidal In2O3 nanocrystals (~6 nm). Sn doping provides free electrons in the conduction band, originating localized surface plasmon resonance (LSPR) and electrical conductivity. The LSPR band can be tuned between 2000 and >3000 nm, depending on the extent and kind of dopant ions. Fe doping, on the other hand, provides unpaired electrons, resulting in weak ferromagnetism at room temperature. Fe doping shifts the LSPR band of 10% Sn doped In2O3 nanocrystals to a longer wavelength along with a reduction in intensity, suggesting trapping of charge carriers around the dopant centers, whereas Sn doping increases the magnetization of 10% Fe-doped In2O3 nanocrystals, probably because of the free electron mediated interactions between distant magnetic ions. The combination of plasmonics and magnetism, in addition to electronic conductivity and visible-light transparency, is a unique feature of our colloidal codoped nanocrystals. PMID- 26279552 TI - Singlet Fission: From Coherences to Kinetics. AB - Singlet fission, in which an initially excited singlet state spontaneously splits into a pair of triplet excitons, is a process that can potentially boost the efficiency of solar energy conversion. The separate electronic bands in organic semiconductors make them especially useful for dividing a high-energy singlet exciton into a pair of lower-energy triplet excitons. Recent experiments illustrate the role of spin coherence in fission, while kinetic models are used to describe how triplet and singlet states interact on longer time scales. Despite insights gained from recent experiments, the detailed structure and dynamics of the electronic states involved in the initial step of singlet fission remain active areas of investigation. On longer time scales, finding ways to efficiently harvest the triplet excitons will be an important challenge for making devices based on this phenomenon. A full understanding of singlet fission requires consideration of a sequence of photophysical events (decoherence, relaxation, and diffusion) occurring on different time scales. PMID- 26279553 TI - Adjusting the Local Arrangement of pi-Stacked Oligothiophenes through Hydrogen Bonds: A Viable Route to Promote Charge Transfer. AB - We show that substituting quaterthiophene cores with strong H-bond aggregators, such as urea groups, provides an efficient way to adjust the mutual in-plane displacements of the semiconducting units and promote charge transfer. Our 2-D structure-property mapping reveals that the insertion of substituents induces up to 2.0 A longitudinal and transversal displacements between the pi-conjugated moieties. Some of these relative displacements lead to improved cofacial orbital overlaps that are otherwise inaccessible due to Pauli repulsion. Our results also emphasize that the fine-tuning of in-plane displacements is more effective than achieving "tighter" packing to promote charge-transfer properties. PMID- 26279554 TI - Ultrafast, Multidimensional Attenuated Total Reflectance Spectroscopy of Adsorbates at Metal Surfaces. AB - Ultrafast dynamics of molecules at solid-liquid interfaces are of outstanding importance in chemistry and physics due to their involvement in processes of heterogeneous catalysis. We present a new spectroscopic approach to resolve coherent, time-resolved, 2D vibrational spectra as well as ultrafast vibrational relaxation dynamics of molecules adsorbed on metallic thin films in contact with liquids. The setup is based on the technique of attenuated total reflectance (ATR) spectroscopy, which is used at interfaces between materials that exhibit different refractive indices. As a sample molecule, we consider carbon monoxide adsorbed in different binding configurations on different metals and resolve its femtosecond vibrational dynamics. It is presented that mid-infrared, multidimensional ATR spectroscopy allows for obtaining a surface-sensitive characterization of adsorbates' vibrational relaxation, spectral diffusion dynamics, and sample inhomogeneity on the femtosecond time scale. PMID- 26279555 TI - Effects of Oxygen-Containing Functional Groups on Supercapacitor Performance. AB - Molecular dynamics (MD) simulations of the interface between graphene and the ionic liquid 1-butyl-3-methylimidazolium trifluoromethanesulfonate (BMIM OTf) were carried out to gain molecular-level insights into the performance of graphene-based supercapacitors and, in particular, determine the effects of the presence of oxygen-containing defects at the graphene surface on their integral capacitance. The MD simulations predict that increasing the surface coverage of hydroxyl groups negatively affects the integral capacitance, whereas the effect of the presence of epoxy groups is much less significant. The calculated variations in capacitance are found to be directly correlated to the interfacial structure. Indeed, hydrogen bonding between hydroxyl groups and SO3 moieties prevents BMIM(+) and OTf(-) ions from interacting favorably in the interfacial layer and restrains the orientation and mobility of OTf(-) ions, thereby reducing the interfacial permittivity of the ionic liquid. The results of the simulations can facilitate the rational design of electrode materials for supercapacitors. PMID- 26279556 TI - Local Orientational Structure of a P3HT pi-pi Conjugated Network Investigated by X-ray Nanodiffraction. AB - We employed nanobeam X-ray diffraction using an X-ray spot size of 150 nm to investigate the local structure of P3HT thin films. We derived nanoscale real space maps of the X-ray diffraction properties at the pi-pi (020) diffraction peak. The X-ray data reveal a complex nanoscale structure of the polymer network with strong local variation where some areas of the film display a rather high degree of angular order. We quantify both the magnitude and direction of the angular order. Our results provide new insights into the local structural properties and connectivity of P3HT films. PMID- 26279557 TI - Advances in Photofunctional Dendrimers for Solar Energy Conversion. AB - Dendrimers are regularly and hierarchically branched synthetic macromolecules with numerous chain ends all emanating from a single core, which makes them attractive candidates for energy conversion applications. During photosynthesis and photocatalysis, photoinduced electron transfer and energy transfer are the main processes involved. Studies on these processes in dendritic systems are critical for the future applications of dendrimers in photochemical energy conversion and other optoelectronic devices. In this Perspective, the recent advances of photofunctional dendrimers in energy conversion based on light harvesting systems, solar cells, and photochemical production of hydrogen will be discussed. The electron-transfer and energy-transfer characteristics in light harvesting photofunctional dendrimers and the regulation of the electron-transfer process and the stabilization of the charge separation state in hydrogen photoproduction are emphasized. PMID- 26279558 TI - Evaluation of the Time-Derivative Coupling for Accurate Electronic State Transition Probabilities from Numerical Simulations. AB - Spikes in the time-derivative coupling (TDC) near surface crossings make the accurate integration of the time-dependent Schrodinger equation in nonadiabatic molecular dynamics simulations a challenge. To address this issue, we present an approximation to the TDC based on a norm-preserving interpolation (NPI) of the adiabatic electronic wave functions within each time step. We apply NPI and two other schemes for computing the TDC in numerical simulations of the Landau-Zener model, comparing the simulated transfer probabilities to the exact solution. Though NPI does not require the analytical calculation of nonadiabatic coupling matrix elements, it consistently yields unsigned population transfer probability errors of ~0.001, whereas analytical calculation of the TDC yields errors of 0.0 1.0 depending on the time step, the offset of the maximum in the TDC from the beginning of the time step, and the coupling strength. The approximation of Hammes-Schiffer and Tully yields errors intermediate between NPI and the analytical scheme. PMID- 26279559 TI - Slow Dynamic Processes in Lead Halide Perovskite Solar Cells. Characteristic Times and Hysteresis. AB - Characteristic times of perovskite solar cells (PSCs) have been measured by different techniques: transient photovoltage decay, transient photoluminescence, and impedance spectroscopy. A slow dynamic process is detected that shows characteristic times in the seconds to milliseconds scale, with good quantitative agreement between transient photovoltage decay and impedance spectroscopy. Here, we show that this characteristic time is related with a novel slow dynamic process caused by the peculiar structural properties of lead halide perovskites and depending on perovskite crystal size and organic cation nature. This new process may lie at the basis of the current-voltage hysteresis reported for PSCs and could have important implications in PSC performance because it may give rise to distinct dynamical behavior with respect to other classes of photovoltaic devices. Furthermore, we show that low-frequency characteristic time, commonly associated with electronic carrier lifetime in other photovoltaic devices, cannot be attributed to a recombination process in the case of PSCs. PMID- 26279560 TI - High-Level, First-Principles, Full-Dimensional Quantum Calculation of the Ro vibrational Spectrum of the Simplest Criegee Intermediate (CH2OO). AB - The ro-vibrational spectrum of the simplest Criegee intermediate (CH2OO) has been determined quantum mechanically based on nine-dimensional potential energy and dipole surfaces for its ground electronic state. The potential energy surface is fitted to more than 50 000 high-level ab initio points with a root-mean-square error of 25 cm(-1), using a recently proposed permutation invariant polynomial neural network method. The calculated rotational constants, vibrational frequencies, and spectral intensities of CH2OO are in excellent agreement with experiment. The potential energy surface provides a valuable platform for studying highly excited vibrational and unimolecular reaction dynamics of this important molecule. PMID- 26279561 TI - Electrochemical Synthesis of Spinel Type ZnCo2O4 Electrodes for Use as Oxygen Evolution Reaction Catalysts. AB - A new electrochemical synthesis route was developed to prepare spinel-type ZnCo2O4 and Co3O4 as high quality thin film-type electrodes for use as electrocatalysts for oxygen evolution reaction (OER). Whereas Co3O4 contains Co(2+) in the tetrahedral sites and Co(3+) in the octahedral sites in the spinel structure, ZnCo2O4 contains only Co(3+) in the octahedral sites; Co(2+) in the tetrahedral sites is replaced by Zn(2+). Therefore, by comparing the catalytic properties of ZnCo2O4 and Co3O4 electrodes prepared with comparable surface morphologies and thicknesses, it was possible to examine whether Co(2+) in Co3O4 is catalytically active for OER. The electrocatalytic properties of ZnCo2O4 and Co3O4 for OER in both 1 M KOH (pH 13.8) and 0.1 M phosphate buffer (pH 7) solutions were investigated and compared. The results suggest that the Co(2+) in Co3O4 is not catalytically critical for OER and ZnCo2O4 can be a more economical and environmentally benign replacement for Co3O4 as an OER catalyst. PMID- 26279562 TI - Surface Isotope Segregation as a Probe of Temperature in Water Nanoclusters. AB - Using ring polymer molecular dynamics simulations, we examine equilibrium and dynamical characteristics of solid-like, aqueous clusters that combine isotopic mixtures of HDO dilute in H2O, at temperatures intermediate between 50 and 175 K. In particular, we focus attention on the relative thermodynamic stabilities of the two isotopes at dangling hydrogen bond sites. The water octamer is analyzed as a reference system. For this aggregate, decreasing temperature yields a gradual stabilization of the light isotope at dangling sites in molecules acting as single-donor-double-acceptors of hydrogen bonds. At T ~ 50 K, the imbalance between the corresponding quantum kinetic energies leads to a free energy difference between dangling and hydrogen bonded sites of the order of ~2kBT. Similar free energy differences were found at dangling sites in Nw = 50 water clusters. The extent of the H/D segregation can be adequately monitored by modifications in the peak intensity of the high frequency shoulder of the stretching band of the infrared spectrum. These signals, in turn, represent a potential experimental signature of the elusive temperature of clusters in molecular beams. PMID- 26279563 TI - Managing Complex Photophysical Pathways for Solar Energy Conversion. PMID- 26279564 TI - Cu Doping in Ligand Free CdS Nanocrystals: Conductivity and Electronic Structure Study. AB - Ligand-free Cu-doped CdS nanocrystals (NCs) have been synthesized to elucidate their surface electronic structure. The Cu-doped ligand-free NCs unlike their undoped counterparts are shown to be luminescent. We used this Cu-related emission as a probe to study the nature of the surface trap states that results in negligible luminescence in the undoped NCs. The concentration of the sulfide ligands is shown to play a crucial role in the surface passivation of the NCs. Electrical conductivity of these NCs was also studied, and they were shown to exhibit significant conductivity of ~10(-4) S cm(-1). Further we have shown that the electrical conductivity is closely correlated to the surface charge and hence the trap states of the individual NCs have far-reaching consequences in the device optimization. PMID- 26279565 TI - Photoinduced Giant Dielectric Constant in Lead Halide Perovskite Solar Cells. AB - Organic-inorganic lead trihalide perovskites have emerged as an outstanding photovoltaic material that demonstrated a high 17.9% conversion efficiency of sunlight to electricity in a short time. We have found a giant dielectric constant (GDC) phenomenon in these materials consisting on a low frequency dielectric constant in the dark of the order of epsilon0 = 1000. We also found an unprecedented behavior in which epsilon0 further increases under illumination or by charge injection at applied bias. We observe that epsilon0 increases nearly linearly with the illumination intensity up to an additional factor 1000 under 1 sun. Measurement of a variety of samples of different morphologies, compositions, and different types of contacts shows that the GDC is an intrinsic property of MAPbX3 (MA = CH3NH3(+)). We hypothesize that the large dielectric response is induced by structural fluctuations. Photoinduced carriers modify the local unit cell equilibrium and change the polarizability, assisted by the freedom of rotation of MA. The study opens a way for the understanding of a key aspect of the photovoltaic operation of high efficiency perovskite solar cells. PMID- 26279566 TI - Genome-wide Reconstruction of OxyR and SoxRS Transcriptional Regulatory Networks under Oxidative Stress in Escherichia coli K-12 MG1655. AB - Three transcription factors (TFs), OxyR, SoxR, and SoxS, play a critical role in transcriptional regulation of the defense system for oxidative stress in bacteria. However, their full genome-wide regulatory potential is unknown. Here, we perform a genome-scale reconstruction of the OxyR, SoxR, and SoxS regulons in Escherichia coli K-12 MG1655. Integrative data analysis reveals that a total of 68 genes in 51 transcription units (TUs) belong to these regulons. Among them, 48 genes showed more than 2-fold changes in expression level under single-TF knockout conditions. This reconstruction expands the genome-wide roles of these factors to include direct activation of genes related to amino acid biosynthesis (methionine and aromatic amino acids), cell wall synthesis (lipid A biosynthesis and peptidoglycan growth), and divalent metal ion transport (Mn(2+), Zn(2+), and Mg(2+)). Investigating the co-regulation of these genes with other stress response TFs reveals that they are independently regulated by stress-specific TFs. PMID- 26279567 TI - GRK2 Fine-Tunes Circadian Clock Speed and Entrainment via Transcriptional and Post-translational Control of PERIOD Proteins. AB - The pacemaker properties of the suprachiasmatic nucleus (SCN) circadian clock are shaped by mechanisms that influence the expression and behavior of clock proteins. Here, we reveal that G-protein-coupled receptor kinase 2 (GRK2) modulates the period, amplitude, and entrainment characteristics of the SCN. Grk2 deficient mice show phase-dependent alterations in light-induced entrainment, slower recovery from jetlag, and longer behavioral rhythms. Grk2 ablation perturbs intrinsic rhythmic properties of the SCN, increasing amplitude and decreasing period. At the cellular level, GRK2 suppresses the transcription of the mPeriod1 gene and the trafficking of PERIOD1 and PERIOD2 proteins to the nucleus. Moreover, GRK2 can physically interact with PERIOD1/2 and promote PERIOD2 phosphorylation at Ser545, effects that may underlie its ability to regulate PERIOD1/2 trafficking. Together, our findings identify GRK2 as an important modulator of circadian clock speed, amplitude, and entrainment by controlling PERIOD at the transcriptional and post-translational levels. PMID- 26279568 TI - Intramolecular C2 Domain-Mediated Autoinhibition of Protein Kinase C betaII. AB - The signaling output of protein kinase C (PKC) is exquisitely controlled, with its disruption resulting in pathophysiologies. Identifying the structural basis for autoinhibition is central to developing effective therapies for cancer, where PKC activity needs to be enhanced, or neurodegenerative diseases, where PKC activity should be inhibited. Here, we reinterpret a previously reported crystal structure of PKCbetaII and use docking and functional analysis to propose an alternative structure that is consistent with previous literature on PKC regulation. Mutagenesis of predicted contact residues establishes that the Ca(2+) sensing C2 domain interacts intramolecularly with the kinase domain and the carboxyl-terminal tail, locking PKC in an inactive conformation. Ca(2+)-dependent bridging of the C2 domain to membranes provides the first step in activating PKC via conformational selection. Although the placement of the C1 domains remains to be determined, elucidation of the structural basis for autoinhibition of PKCbetaII unveils a unique direction for therapeutically targeting PKC. PMID- 26279569 TI - Cuticular Hydrocarbon Pheromones for Social Behavior and Their Coding in the Ant Antenna. AB - The sophisticated organization of eusocial insect societies is largely based on the regulation of complex behaviors by hydrocarbon pheromones present on the cuticle. We used electrophysiology to investigate the detection of cuticular hydrocarbons (CHCs) by female-specific olfactory sensilla basiconica on the antenna of Camponotus floridanus ants through the utilization of one of the largest family of odorant receptors characterized so far in insects. These sensilla, each of which contains multiple olfactory receptor neurons, are differentially sensitive to CHCs and allow them to be classified into three broad groups that collectively detect every hydrocarbon tested, including queen and worker-enriched CHCs. This broad-spectrum sensitivity is conserved in a related species, Camponotus laevigatus, allowing these ants to detect CHCs from both nestmates and non-nestmates. Behavioral assays demonstrate that these ants are excellent at discriminating CHCs detected by the antenna, including enantiomers of a candidate queen pheromone that regulates the reproductive division of labor. PMID- 26279570 TI - BDNF Reduces Toxic Extrasynaptic NMDA Receptor Signaling via Synaptic NMDA Receptors and Nuclear-Calcium-Induced Transcription of inhba/Activin A. AB - The health of neurons is critically dependent on the relative signaling intensities of survival-promoting synaptic and death-inducing extrasynaptic NMDA receptors. Here, we show that BDNF is a regulator of this balance and promotes neuroprotection by reducing toxic NMDA receptor signaling. BDNF acts by initiating synaptic NMDA-receptor/nuclear-calcium-driven adaptogenomics, leading to increased expression of inhibin beta-A (inhba). Inhibin beta-A (its homodimer is known as activin A) in turn reduces neurotoxic extrasynaptic NMDA-receptor mediated calcium influx, thereby shielding neurons against mitochondrial dysfunction, a major cause of excitotoxicity. Thus, BDNF induces acquired neuroprotection by enhancing synaptic activity and lowering extrasynaptic NMDA receptor death signaling through a nuclear calcium-inhibin beta-A pathway. This process, which confers protection against ischemic brain damage in a mouse stroke model, may be compromised in Huntington's disease, Alzheimer's disease, or aging related neurodegenerative conditions that are associated with reduced BDNF levels and/or enhanced extrasynaptic NMDA receptor signaling. PMID- 26279571 TI - Amyloid-beta Oligomers May Impair SNARE-Mediated Exocytosis by Direct Binding to Syntaxin 1a. AB - Alzheimer's disease (AD) is closely associated with synaptic dysfunction, and thus current treatments often aim to stimulate neurotransmission to improve cognitive impairment. Whereas the formation of the soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) complex is essential for synaptic transmission, the correlation between SNAREs and AD neuropathology is unknown. Here, we report that intracellular amyloid-beta (Abeta) oligomers directly inhibit SNARE-mediated exocytosis by impairing SNARE complex formation. We observe abnormal reduction of SNARE complex levels in the brains of APP/PS1 transgenic (TG) mice compared to age-matched wild-types. We demonstrate that Abeta oligomers block SNARE complex assembly through the direct interaction with a target membrane (t)-SNARE syntaxin 1a in vitro. Furthermore, the results of the in vitro single-vesicle content-mixing assay reveal that Abeta oligomers inhibit SNARE-mediated fusion pores. Thus, our study identifies a potential molecular mechanism by which intracellular Abeta oligomers hamper SNARE-mediated exocytosis, likely leading to AD-associated synaptic dysfunctions. PMID- 26279573 TI - Sox9 Activation Highlights a Cellular Pathway of Renal Repair in the Acutely Injured Mammalian Kidney. AB - After acute kidney injury (AKI), surviving cells within the nephron proliferate and repair. We identify Sox9 as an acute epithelial stress response in renal regeneration. Translational profiling after AKI revealed a rapid upregulation of Sox9 within proximal tubule (PT) cells, the nephron cell type most vulnerable to AKI. Descendants of Sox9(+) cells generate the bulk of the nephron during development and regenerate functional PT epithelium after AKI-induced reactivation of Sox9 after renal injury. After restoration of renal function post AKI, persistent Sox9 expression highlights regions of unresolved damage within injured nephrons. Inactivation of Sox9 in PT cells pre-injury indicates that Sox9 is required for the normal course of post-AKI recovery. These findings link Sox9 to cell intrinsic mechanisms regulating development and repair of the mammalian nephron. PMID- 26279572 TI - Intestinal Monocyte-Derived Macrophages Control Commensal-Specific Th17 Responses. AB - Generation of different CD4 T cell responses to commensal and pathogenic bacteria is crucial for maintaining a healthy gut environment, but the associated cellular mechanisms are poorly understood. Dendritic cells (DCs) and macrophages (Mfs) integrate microbial signals and direct adaptive immunity. Although the role of DCs in initiating T cell responses is well appreciated, how Mfs contribute to the generation of CD4 T cell responses to intestinal microbes is unclear. Th17 cells are critical for mucosal immune protection and at steady state are induced by commensal bacteria, such as segmented filamentous bacteria (SFB). Here, we examined the roles of mucosal DCs and Mfs in Th17 induction by SFB in vivo. We show that Mfs, and not conventional CD103(+) DCs, are essential for the generation of SFB-specific Th17 responses. Thus, Mfs drive mucosal T cell responses to certain commensal bacteria. PMID- 26279574 TI - MIWI2 and MILI Have Differential Effects on piRNA Biogenesis and DNA Methylation. AB - In developing male germ cells, prospermatogonia, two Piwi proteins, MILI and MIWI2, use Piwi-interacting RNA (piRNA) guides to repress transposable element (TE) expression and ensure genome stability and proper gametogenesis. In addition to their roles in post-transcriptional TE repression, both proteins are required for DNA methylation of TE sequences. Here, we analyzed the effect of Miwi2 deficiency on piRNA biogenesis and transposon repression. Miwi2 deficiency had only a minor impact on piRNA biogenesis; however, the piRNA profile of Miwi2 knockout mice indicated overexpression of several LINE1 TE families that led to activation of the ping-pong piRNA cycle. Furthermore, we found that MILI and MIWI2 have distinct functions in TE repression in the nucleus. MILI is responsible for DNA methylation of a larger subset of TE families than MIWI2 is, suggesting that the proteins have independent roles in establishing DNA methylation patterns. PMID- 26279575 TI - Amino Acid Activation of mTORC1 by a PB1-Domain-Driven Kinase Complex Cascade. AB - The mTORC1 complex is central to the cellular response to changes in nutrient availability. The signaling adaptor p62 contributes to mTORC1 activation in response to amino acids and interacts with TRAF6, which is required for the translocation of mTORC1 to the lysosome and the subsequent K63 polyubiquitination and activation of mTOR. However, the signal initiating these p62-driven processes was previously unknown. Here, we show that p62 is phosphorylated via a cascade that includes MEK3/6 and p38delta and is driven by the PB1-containing kinase MEKK3. This phosphorylation results in the recruitment of TRAF6 to p62, the ubiquitination and activation of mTOR, and the regulation of autophagy and cell proliferation. Genetic inactivation of MEKK3 or p38delta mimics that of p62 in that it leads to inhibited growth of PTEN-deficient prostate organoids. Analysis of human prostate cancer samples showed upregulation of these three components of the pathway, which correlated with enhanced mTORC1 activation. PMID- 26279577 TI - cis Determinants of Promoter Threshold and Activation Timescale. AB - Although the relationship between DNA cis-regulatory sequences and gene expression has been extensively studied at steady state, how cis-regulatory sequences affect the dynamics of gene induction is not known. The dynamics of gene induction can be described by the promoter activation timescale (AcTime) and amplitude threshold (AmpThr). Combining high-throughput microfluidics with quantitative time-lapse microscopy, we control the activation dynamics of the budding yeast transcription factor, Msn2, and reveal how cis-regulatory motifs in 20 promoter variants of the Msn2-target-gene SIP18 affect AcTime and AmpThr. By modulating Msn2 binding sites, we can decouple AmpThr from AcTime and switch the SIP18 promoter class from high AmpThr and slow AcTime to low AmpThr and either fast or slow AcTime. We present a model that quantitatively explains gene induction dynamics on the basis of the Msn2-binding-site number, TATA box location, and promoter nucleosome organization. Overall, we elucidate the cis regulatory logic underlying promoter decoding of TF dynamics. PMID- 26279576 TI - Deregulation of the Ras-Erk Signaling Axis Modulates the Enhancer Landscape. AB - Unrestrained receptor tyrosine kinase (RTK) signaling and epigenetic deregulation are root causes of tumorigenesis. We establish linkage between these processes by demonstrating that aberrant RTK signaling unleashed by oncogenic HRas(G12V) or loss of negative feedback through Sprouty gene deletion remodels histone modifications associated with active typical and super-enhancers. However, although both lesions disrupt the Ras-Erk axis, the expression programs, enhancer signatures, and transcription factor networks modulated upon HRas(G12V) transformation or Sprouty deletion are largely distinct. Oncogenic HRas(G12V) elevates histone 3 lysine 27 acetylation (H3K27ac) levels at enhancers near the transcription factor Gata4 and the kinase Prkcb, as well as their expression levels. We show that Gata4 is necessary for the aberrant gene expression and H3K27ac marking at enhancers, and Prkcb is required for the oncogenic effects of HRas(G12V)-driven cells. Taken together, our findings demonstrate that dynamic reprogramming of the cellular enhancer landscape is a major effect of oncogenic RTK signaling. PMID- 26279579 TI - Tuning of the excitation wavelength in Eu(3+)-aminophenyl based polyfluorinated beta-diketonate complexes: a red-emitting Eu(3+)-complex encapsulated in a silica/polymer hybrid material excited by blue light. AB - We describe herein the synthesis, characterization and photophysical properties of a series of europium complexes based on three aminophenyl based polyfluorinated beta-diketonates, namely, 1-(4-aminophenyl)-4,4,5,5,5-pentafluoro 3-hydroxypent-2-en-1-one, 1-(4-(dimethylamino)phenyl)-4,4,5,5,5-pentafluoro-3 hydroxypent-2-en-1-one and 1-(4-(diphenylamino)phenyl)-4,4,5,5,5-pentafluoro-3 hydroxypent-2-en-1-one, and an ancillary ligand, 4,5-bis(diphenylphosphino)-9,9 dimethylxanthene oxide. The results demonstrated that the triphenylamine based polyfluorinated Eu(3+)-beta-diketonate complexes dramatically red-shifted the excitation maximum to the visible region (lambdaex, max = 400 nm) with an impressive quantum yield (40%) as compared to the simple Eu(3+)-aminophenyl-beta diketonate complexes (lambdaex, max = 370 nm). This can be explained on the basis of the conjugation between nitrogen lone pair electrons and the phenyl pi electrons in the beta-diketonate ligand system. On the other hand, the electron donating dimethylamino group (Hammett constant: sigmap = -0.83) containing Eu(3+) beta-diketonate complexes moderately shifted the excitation maximum in the UV region from 370 to 380 nm as compared to unsubstituted aminophenyl (Hammett constant: sigmap = -0.66) Eu(3+) complexes. The displacement of water molecules in aminophenyl based Eu(3+)-beta-diketonate binary complexes by a rigid phosphine oxide ligand richly enhances the photoluminescence quantum yields as well as the excited state lifetime values of the corresponding ternary complexes. As an integral part of this work, hybrid materials have been developed through a sol gel route by encapsulating a ternary Eu(3+) compound in a silica/polymer hybrid for high performance luminescence applications. In addition, a bright red emitting diode was fabricated by coating the designed hybrid material onto a 400 nm emitting InGaN chip and the photoluminescence was examined. Notably, the current study clearly shows that the developed triphenylamine based Eu(3+)-beta diketonate complex is an interesting red-emitting material excited by blue light and therefore may find potential applications in the fields of biological and materials science. PMID- 26279578 TI - Lactobacilli Modulate Epithelial Cytoprotection through the Nrf2 Pathway. AB - An optimal gut microbiota influences many beneficial processes in the metazoan host. However, the molecular mechanisms that mediate and function in symbiont induced host responses have not yet been fully characterized. Here, we report that cellular ROS enzymatically generated in response to contact with lactobacilli in both mice and Drosophila has salutary effects against exogenous insults to the intestinal epithelium via the activation of Nrf2 responsive cytoprotective genes. These data show that the xenobiotic-inducible Nrf2 pathway participates as a signaling conduit between the prokaryotic symbiont and the eukaryotic host. Indeed, our data imply that the capacity of lactobacilli to induce redox signaling in epithelial cells is a highly conserved hormetic adaptation to impel cellular conditioning to exogenous biotic stimuli. These data also highlight the role the microbiota plays in eukaryotic cytoprotective pathways and may have significant implications in the characterization of a eubiotic microbiota. PMID- 26279580 TI - Acute consumption of a caffeinated energy drink enhances aspects of performance in sprint swimmers. AB - This study investigated the effect of a caffeinated energy drink on various aspects of performance in sprint swimmers. In a randomised and counterbalanced order, fourteen male sprint swimmers performed two acute experimental trials after the ingestion of a caffeinated energy drink (3 mg/kg) or after the ingestion of the same energy drink without caffeine (0 mg/kg; placebo). After 60 min of ingestion of the beverages, the swimmers performed a countermovement jump, a maximal handgrip test, a 50 m simulated competition and a 45 s swim at maximal intensity in a swim ergometer. A blood sample was withdrawn 1 min after the completion of the ergometer test. In comparison with the placebo drink, the intake of the caffeinated energy drink increased the height in the countermovement jump (49.4 (SD 5.3) v. 50.9 (SD 5.2) cm, respectively; P<0.05) and maximal force during the handgrip test with the right hand (481 (SD 49) v. 498 (SD 43) N; P<0.05). Furthermore, the caffeinated energy drink reduced the time needed to complete the 50 m simulated swimming competition (27.8 (SD 3.4) v. 27.5 (SD 3.2) s; P<0.05), and it increased peak power (273 (SD 55) v. 303 (SD 49) W; P <0.05) and blood lactate concentration (11.0 (SD 2.0) v. 11.7 (SD 2.1) mM; P<0.05) during the ergometer test. The caffeinated energy drink did not modify the prevalence of insomnia (7 v. 7%), muscle pain (36 v. 36%) or headache (0 v. 7%) during the hours following its ingestion (P>0.05). A caffeinated energy drink increased some aspects of swimming performance in competitive sprinters, whereas the side effects derived from the intake of this beverage were marginal at this dosage. PMID- 26279582 TI - RANZCOG CREI Consensus Statement on treatment of Ovarian Hyperstimulation Syndrome. AB - BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is an uncommon but important iatrogenic condition associated with considerable morbidity and a small risk of mortality. This document gathers the consensus of a group of fertility subspecialists to aid health professionals in the development of protocols and guidelines for the management of women with OHSS. AIM: To produce evidence-based consensus statements on the treatment of ovarian hyperstimulation syndrome (OHSS). METHODS: The CREI Consensus Group met in 2013 and 2014 and identified issues for inclusion and review. Review of the available evidence was conducted and consensus statements prepared. Areas of dissent of expert opinion and for further research were noted. RESULTS: There is a paucity of good data regarding the treatment of this condition, and much of the treatment is supportive in nature. Most of the management recommendations are based on good clinical practice points, rather than evidence from randomised trials. CONCLUSION: OHSS is an uncommon but serious condition for which there are a number of proven preventative strategies. Once OHSS is present, the treatment of OHSS is mainly supportive, and more research is required to elucidate treatment options targeted specifically at the main causative factors, to better treat the condition. PMID- 26279583 TI - Approaching the Hole Mobility Limit of GaSb Nanowires. AB - In recent years, high-mobility GaSb nanowires have received tremendous attention for high-performance p-type transistors; however, due to the difficulty in achieving thin and uniform nanowires (NWs), there is limited report until now addressing their diameter-dependent properties and their hole mobility limit in this important one-dimensional material system, where all these are essential information for the deployment of GaSb NWs in various applications. Here, by employing the newly developed surfactant-assisted chemical vapor deposition, high quality and uniform GaSb NWs with controllable diameters, spanning from 16 to 70 nm, are successfully prepared, enabling the direct assessment of their growth orientation and hole mobility as a function of diameter while elucidating the role of sulfur surfactant and the interplay between surface and interface energies of NWs on their electrical properties. The sulfur passivation is found to efficiently stabilize the high-energy NW sidewalls of (111) and (311) in order to yield the thin NWs (i.e., <40 nm in diameters) with the dominant growth orientations of ?211? and ?110?, whereas the thick NWs (i.e., >40 nm in diameters) would grow along the most energy-favorable close-packed planes with the orientation of ?111?, supported by the approximate atomic models. Importantly, through the reliable control of sulfur passivation, growth orientation and surface roughness, GaSb NWs with the peak hole mobility of ~400 cm(2)V s(-1) for the diameter of 48 nm, approaching the theoretical limit under the hole concentration of ~2.2 * 10(18) cm(-3), can be achieved for the first time. All these indicate their promising potency for utilizations in different technological domains. PMID- 26279584 TI - Intrasexual selection drives sensitivity to pitch, formants and duration in the competitive calls of fallow bucks. AB - BACKGROUND: Mammal vocal parameters such as fundamental frequency (or pitch; f o ) and formant dispersion often provide information about quality traits of the producer (e.g. dominance and body size), suggesting that they are sexually selected. However, little experimental evidence exists demonstrating the importance of these cues in intrasexual competition, particularly f o . Male Fallow deer (bucks) produce an extremely low pitched groan. Bucks have a descended larynx and generate f o well below what is expected for animals of their size. Groan parameters are linked to caller dominance, body size and condition, suggesting that groans are the product of sexual selection. Using a playback experiment, we presented bucks with groans that had been manipulated to alter vocal cues to these male characteristics and compared the response to the same, non-modified (natural) groans. RESULTS: We experimentally examined the ability of bucks to utilise putative cues to dominance (f o ), body size (formant frequencies) and condition (groan duration), when assessing competitors. We found that bucks treated groans with lowered f o (more dominant), and lowered formant frequencies (larger caller) as more threatening. By contrast, groans with raised formant frequencies (smaller caller), and shorter durations (more fatigued caller) were treated as less threatening. CONCLUSIONS: Our results indicate that intrasexual selection is driving groans to concurrently convey caller dominance, body size and condition. They represent the first experimental demonstration of the importance of f o in male competition in non-human mammals, and show that bucks have advanced perception abilities that allow them to extract information based on relatively small changes in key parameters. PMID- 26279586 TI - 27.6. A 0.7pF-to-10nF Fully Digital Capacitance-to-Digital Converter Using Iterative Delay-Chain Discharge. PMID- 26279585 TI - Shades of Decay: The Meanings of Tooth Discoloration and Deterioration to Mexican Immigrant Caregivers of Young Children. AB - The objective of this article is to investigate parental understanding of tooth discoloration and decay and their related care seeking for young, Mexican American children. The research design entailed semi-structured, face-to-face interviews conducted in Spanish with a convenience sample of 37 Mexican immigrant mothers of young children in a low-income urban neighborhood. Five major color terms - white, off-white, yellow, brown, and black - were used to describe tooth discoloration, the causes of which were mainly unrecognized or attributed to poor oral hygiene and exposure to sweet substances. Mothers also described three major levels of deterioration of the structural integrity of teeth due to caries, from stains to decayed portions to entirely rotten. A trend was observed between use of darker discoloration terms and extensive carious lesions. Teeth described as both dark in color and structurally damaged resulted in seeking of professional care. The paper concludes with the finding that Spanish terms used to describe tooth discoloration and carious lesions are broad and complex. Mexican immigrant mothers' interpretations of tooth discoloration and decay may differ from dental professionals' and result in late care seeking. Increased understanding between dental practitioners and caregivers is needed to create educational messages about the early signs of tooth decay. PMID- 26279587 TI - Low Academic Competence in First Grade as a Risk Factor for Depressive Cognitions and Symptoms in Middle School. AB - The present study investigated the role of low academic competence in the emergence of depressive cognitions and symptoms. Structural equation modeling was conducted on a longitudinal sample of African American boys (n = 253) and girls (n = 221). Results supported the hypothesized path models from academic competence in 1st grade to depressive symptoms in 7th grade, controlling for a host of correlated constructs (conduct problems, inattention, social problems). Perceived control in 6th grade mediated the effect of academic competence on depressive symptoms. Although the models fit the data well for both boys and girls, the path coefficients were notably larger for girls; in particular, multiple-group analysis revealed a statistically stronger effect of low academic competence on perceptions of control for girls. The study and findings fit well with counseling psychologists' commitment to prevention activities and to culture specific research. Implications for designing interventions and prevention strategies for children with early academic problems are discussed. PMID- 26279588 TI - Preparation of fluorinated RNA nucleotide analogs potentially stable to enzymatic hydrolysis in RNA and DNA polymerase assays. AB - Analogs of ribonucleotides (RNA) stable to enzymatic hydrolysis were prepared and characterized. Computational investigations revealed that this class of compounds with a modified triphosphate exhibits the correct polarity and minimal steric effects compared to the natural molecule. Non-hydrolysable properties as well as the ability of the modified nucleotide to be recognized by enzymes were probed by performing single-turnover gap filling assays with T7 RNA polymerase and DNA polymerase beta. PMID- 26279589 TI - Classifier Design Given an Uncertainty Class of Feature Distributions via Regularized Maximum Likelihood and the Incorporation of Biological Pathway Knowledge in Steady-State Phenotype Classification. AB - Contemporary high-throughput technologies provide measurements of very large numbers of variables but often with very small sample sizes. This paper proposes an optimization-based paradigm for utilizing prior knowledge to design better performing classifiers when sample sizes are limited. We derive approximate expressions for the first and second moments of the true error rate of the proposed classifier under the assumption of two widely-used models for the uncertainty classes; epsilon-contamination and p-point classes. The applicability of the approximate expressions is discussed by defining the problem of finding optimal regularization parameters through minimizing the expected true error. Simulation results using the Zipf model show that the proposed paradigm yields improved classifiers that outperform traditional classifiers that use only training data. Our application of interest involves discrete gene regulatory networks possessing labeled steady-state distributions. Given prior operational knowledge of the process, our goal is to build a classifier that can accurately label future observations obtained in the steady state by utilizing both the available prior knowledge and the training data. We examine the proposed paradigm on networks containing NF-kappaB pathways, where it shows significant improvement in classifier performance over the classical data-only approach to classifier design. Companion website: http://gsp.tamu.edu/Publications/supplementary/shahrokh12a. PMID- 26279590 TI - Defining Success in Adult Basic Education Settings: Multiple Stakeholders, Multiple Perspectives. AB - This study employed quantitative and qualitative research approaches to investigate what constitutes "success" in Adult Basic Education (ABE) programs from the perspectives of multiple educational stakeholders: the state funding agency, the teachers, and the students. Success was defined in multiple ways. In the quantitative section of the study, we computed classroom value-added scores (used as a metric of the state's definition of success) to identify more and less effective ABE classrooms in two Florida counties. In the qualitative section of the study, we observed and conducted interviews with teachers and students in the selected classrooms to investigate how these stakeholders defined success in ABE. Iterative consideration of the qualitative data revealed three principal markers of success: (a) instructional strategies and teacher-student interactions; (b) views on standardized testing; and (c) student motivational factors. In general, classrooms with higher value-added scores were characterized by multiple instructional approaches, positive and collaborative teacher-student interactions, and students engaging in goal setting and citing motivational factors such as family and personal fulfillment. The implications for ABE programs are discussed. PMID- 26279591 TI - Branched/linear selectivity in palladium-catalyzed allyl-allyl cross-couplings: The role of ligands. AB - While Pd-catalyzed allyl-allyl cross-couplings in the presence of small-bite angle bidentate ligands reliably furnish the branched regioisomer with high levels of selectivity, cross-couplings in the presence of large-bite-angle bidentate ligands give varying, often unpredictable, levels of selectivity. In a combined computational and experimental study, we probe the underlying features that govern the regioselectivity in these metal-catalyzed cross-couplings. PMID- 26279592 TI - Understanding Racial Differences in Deceased-Donor Kidney Transplantation: Geography, Poverty, Language, and Health Insurance Coverage. AB - Despite the continued growth of diverse populations on dialysis, no prior studies have comprehensively compared the barriers to kidney transplantation among different racial and ethnic groups. This brief review summarizes key findings from a recent study that examined specific determinants of diminished access to, or delayed completion of, deceased-donor kidney transplantation among major racial-ethnic groups in the United States. In particular, we focus on the relative influence on transplantation rates of clinical factors, such as histocompatibility, residential geography, health insurance coverage, poverty, and other socioeconomic factors according to patient race or ethnicity. PMID- 26279593 TI - On the Estimation of Disability-Free Life Expectancy: Sullivan' Method and Its Extension. AB - A rapidly aging population, such as the United States today, is characterized by the increased prevalence of chronic impairment. Robust estimation of disability free life expectancy (DFLE), or healthy life expectancy, is essential for examining whether additional years of life are spent in good health and whether life expectancy is increasing faster than the decline of disability rates. Over 30 years since its publication, Sullivan's method remains the most widely used method to estimate DFLE. Therefore, it is surprising to note that Sullivan did not provide any formal justification of his method. Debates in the literature have centered around the properties of Sullivan's method and have yielded conflicting results regarding the assumptions required for Sullivan's method. In this article we establish a statistical foundation of Sullivan's method. We prove that, under stationarity assumptions, Sullivan's estimator is unbiased and consistent. This resolves the debate in the literature, which has generally concluded that additional assumptions are necessary. We also show that the standard variance estimator is consistent and approximately unbiased. Finally, we demonstrate that Sullivan's method can be extended to estimate DFLE without stationarity assumptions. Such an extension is possible whenever a cohort life table and either consecutive cross-sectional disability surveys or a longitudinal survey are available. Our empirical analysis of the 1907 and 1912 U.S. birth cohorts suggests that while mortality rates remain approximately stationary, disability rates decline during this time period. PMID- 26279594 TI - A Two-Sample Test for Equality of Means in High Dimension. AB - We develop a test statistic for testing the equality of two population mean vectors in the "large-p-small-n" setting. Such a test must surmount the rank deficiency of the sample covariance matrix, which breaks down the classic Hotelling T2 test. The proposed procedure, called the generalized component test, avoids full estimation of the covariance matrix by assuming that the p components admit a logical ordering such that the dependence between components is related to their displacement. The test is shown to be competitive with other recently developed methods under ARMA and long-range dependence structures and to achieve superior power for heavy-tailed data. The test does not assume equality of covariance matrices between the two populations, is robust to heteroscedasticity in the component variances, and requires very little computation time, which allows its use in settings with very large p. An analysis of mitochondrial calcium concentration in mouse cardiac muscles over time and of copy number variations in a glioblastoma multiforme data set from The Cancer Genome Atlas are carried out to illustrate the test. PMID- 26279595 TI - Anticipating Their Future: Adolescent Values for the Future Predict Adult Behaviors. AB - Adolescent future values - beliefs about what will matter to them in the future - may shape their adult behavior. Utilizing a national longitudinal British sample, this study examined whether adolescent future values in six domains (i.e., family responsibility, full-time job, personal responsibility, autonomy, civic responsibility, and hedonistic privilege) predicted adult social roles, civic behaviors, and alcohol use. Future values positively predicted behaviors within the same domain; fewer cross-domain associations were evident. Civic responsibility positively predicted adult civic behaviors, but negatively predicted having children. Hedonistic privilege positively predicted adult alcohol use and negatively predicted civic behaviors. Results suggest that attention should be paid to how adolescents are thinking about their futures due to the associated links with long-term social and health behaviors. PMID- 26279596 TI - The Impact of Social Security on Return Migration among Latin American Elderly in the U.S. AB - International migration has long been considered the preserve of working-age adults. However, the rapid diversification of the elderly population calls for increased attention to the migration patterns of this group and its possible motivations. This study examines whether Latin American immigrants who are primary Social Security beneficiaries are more likely to return to their home countries during later life if they receive lower Social Security benefits. Using a regression discontinuity approach on restricted data from the U.S. Social Security Administration (N=1,515), this study presents the results of a natural experiment whereby the Social Security Administration unexpectedly lowered the Social Security benefits of the 1917-1921 birth cohorts due to a miscalculation in the benefit-calculation formula. Results suggest that approximately 10% of primary Social Security beneficiaries from Latin America born close to these dates return migrated, the probability of which was not affected by Social Security benefit levels. PMID- 26279597 TI - Quantitative ethnographic study of physician workflow and interactions with electronic health record systems. AB - This study explores the relationship between primary care physicians' interactions with health information technology and primary care workflow. Clinical encounters were recorded with high-resolution video cameras to capture physicians' workflow and interaction with two objects of interest, the electronic health record (EHR) system, and their patient. To analyze the data, a coding scheme was developed based on a validated list of primary care tasks to define the presence or absence of a task, the time spent on each task, and the sequence of tasks. Results revealed divergent workflows and significant differences between physicians' EHR use surrounding common workflow tasks: gathering information, documenting information, and recommend/discuss treatment options. These differences suggest impacts of EHR use on primary care workflow, and capture types of workflows that can be used to inform future studies with larger sample sizes for more effective designs of EHR systems in primary care clinics. Future research on this topic and design strategies for effective health information technology in primary care are discussed. PMID- 26279598 TI - Boy or Girl? Maternal Psychological Correlates of Knowing Fetal Sex. AB - Ultrasound provides a reliable, convenient way to determine fetal sex, but not all expectant mothers pursue this knowledge. We used logistic regression to investigate whether maternal personality, parenting perfectionism, and gender role beliefs were associated with knowing fetal sex in a recent sample of first time expectant mothers. We also tested whether conscientiousness and extraversion moderated the association between gender role beliefs and knowing fetal sex. Mothers who were more open to experience were less likely to know fetal sex, whereas mothers high in parenting perfectionism were more likely to know fetal sex. Conscientious mothers who espoused more egalitarian gender role beliefs were less likely to know fetal sex. PMID- 26279599 TI - Perceptual asymmetry and youths' responses to stress: Understanding vulnerability to depression. AB - This research examined the hypothesis that reduced posterior right hemisphere activity interferes with the regulation of emotions and behavior in response to stress, creating vulnerability to depression. Consistent with a diathesis-stress model, we predicted that youth with a reduced posterior right hemisphere bias in emotional processing would engage in less adaptive responses to stress, which would be associated with depressive symptoms in those who reported the recent experience of high, but not low, levels of stress. Participants were 510 4th through 8th graders who completed the Chimeric Faces Task and measures of responses to stress and depressive symptoms. Results supported the idea that responses to stress account for the association between reduced posterior right hemisphere activity and depressive symptoms in youth who report high, but not low, levels of stress. This study provides insight into one process through which reduced posterior right hemisphere activity may confer vulnerability to depressive symptoms, and implicates responses to stress as a target for intervention. PMID- 26279600 TI - Needle path planning and steering in a three-dimensional non-static environment using two-dimensional ultrasound images. AB - Needle insertion is commonly performed in minimally invasive medical procedures such as biopsy and radiation cancer treatment. During such procedures, accurate needle tip placement is critical for correct diagnosis or successful treatment. Accurate placement of the needle tip inside tissue is challenging, especially when the target moves and anatomical obstacles must be avoided. We develop a needle steering system capable of autonomously and accurately guiding a steerable needle using two-dimensional (2D) ultrasound images. The needle is steered to a moving target while avoiding moving obstacles in a three-dimensional (3D) non static environment. Using a 2D ultrasound imaging device, our system accurately tracks the needle tip motion in 3D space in order to estimate the tip pose. The needle tip pose is used by a rapidly exploring random tree-based motion planner to compute a feasible needle path to the target. The motion planner is sufficiently fast such that replanning can be performed repeatedly in a closed loop manner. This enables the system to correct for perturbations in needle motion, and movement in obstacle and target locations. Our needle steering experiments in a soft-tissue phantom achieves maximum targeting errors of 0.86 +/ 0.35 mm (without obstacles) and 2.16 +/- 0.88 mm (with a moving obstacle). PMID- 26279601 TI - Thermal thresholds of the predatory mite Balaustium hernandezi. AB - The lower and upper thermal activity thresholds of adult and larval Balaustium hernandezi von Heyden (Acari: Erythraeidae) are compared with those of its prey Tetranychus urticae Koch (Acari: Tetranychidae). Adult female B. hernandezi retain ambulatory function (CTmin) and movement of appendages (chill coma) at significantly lower temperatures (5.9 and -2.1 degrees C, respectively) than those of larval B. hernandezi (8.1 and -1.7 degrees C) and T. urticae (10.6 and 10.3 degrees C). There is no significant difference between the temperature at which adult and larval B. hernandezi and T. urticae cease walking as the temperature is raised (CTmax) (46.7, 46.3 and 47.3 degrees C, respectively). However, both life stages of B. hernandezi cease movement (heat coma) below the upper locomotory limits of T. urticae (46.8, 46.7 and 48.7 degrees C, respectively). Adult B. hernandezi have significantly faster walking speeds than larvae and T. urticae across a range of temperatures. The lower thermal activity threshold data indicate that B. hernandezi would make an effective biological control agent in temperate climates; however, the extent of the low temperature tolerances of the species suggests the potential to establish in a northern European climate. PMID- 26279602 TI - A tale of two haplotype groups: Evaluating the New World Junonia ring species hypothesis using the distribution of divergent COI haplotypes. AB - The New World Junonia butterflies are a possible ring species with a circum Caribbean distribution. Previous reports suggest a steady transition between North and South American forms in Mesoamerica, but in Cuba the forms were thought to co-exist without interbreeding representing the overlapping ends of the ring. Three criteria establish the existence of a ring species: a ring-shaped geographic distribution, gene flow among intervening forms, and genetic isolation in the region of range overlap. We evaluated mitochondrial cytochrome oxidase I haplotypes in Junonia from 9 species in the Western Hemisphere to test the Junonia ring species hypothesis. Junonia species are generally not monophyletic with respect to COI haplotypes, which are shared across species. However, two major COI haplotype groups exist. Group A predominates in South America, and Group B predominates in North and Central America. Therefore, COI haplotypes can be used to assess the degree of genetic influence a population receives from each continent. Junonia shows a ring-shaped distribution around the Caribbean, and evidence is consistent with gene flow among forms of Junonia, including those from Mesoamerica. However, we detected no discontinuity in gene flow in Cuba or elsewhere in the Caribbean consistent with genetic isolation in the region of overlap. Though sampling is still very limited in the critical region, the only remaining possiblity for a circum-Caribbean discontinuity in gene flow is at the Isthmus of Panama, where there may be a transition from 98% Group B haplotypes in Costa Rica to 85-100% Group A haplotypes in South America. PMID- 26279603 TI - In Vitro and in Vivo Anti-Diabetic Effects of Anthocyanins from Maqui Berry (Aristotelia chilensis). AB - We used a murine model of type II diabetes, which reproduces the major features of the human disease, and a number of cellular models to study the antidiabetic effect of ANC, a standardised anthocyanin-rich formulation from maqui berry (Aristotelia chilensis). We also isolated delphinidin 3-sambubioside-5-glucoside (D3S5G), a characteristic anthocyanin from maqui berry, and studied its antidiabetic properties. We observed that oral administration of ANC improved fasting blood glucose levels and glucose tolerance in hyperglycaemic obese C57BL/6J mice fed a high fat diet. In H4IIE rat liver cells, ANC decreased glucose production and enhanced the insulin-stimulated down regulation of the gluconeogenic enzyme, glucose-6-phosphatase. In L6 myotubes ANC treatment increased both insulin and non-insulin mediated glucose uptake. As with the ACN, oral administration of pure D3S5G dose-dependently decreased fasting blood glucose levels in obese C57BL/6J mice, and decreased glucose production in rat liver cells. D3S5G also increased glucose uptake in L6 myotubes and is at least partially responsible for ANC's anti-diabetic properties. PMID- 26279604 TI - Cofoundress relatedness and group productivity in colonies of social Dunatothrips (Insecta: Thysanoptera) on Australian Acacia. AB - Facultative joint colony founding by social insects provides opportunities to analyze the roles of genetic and ecological factors in the evolution of cooperation. Although cooperative nesting is observed in range of social insect taxa, the most detailed studies of this behavior have been conducted with Hymenoptera (ants, bees, and wasps). Here, we show that foundress associations in the haplodiploid social thrips Dunatothrips aneurae (Insecta: Thysanoptera) are most often comprised of close relatives (sisters), though groups with unrelated foundresses are also found. Associations among relatives appear to be facilitated by limited female dispersal, which results in viscous population structure. In addition, we found that per capita productivity declined with increasing group size, sex ratios were female-biased, and some female offspring apparently remained in their natal domicile for some time following eclosion. D. aneurae thus exhibits a suite of similarities with eusocial Hymenoptera, providing evidence for the convergent evolution of associated social and life-history traits in Hymenoptera and Thysanoptera. PMID- 26279605 TI - Trading or coercion? Variation in male mating strategies between two communities of East African chimpanzees. AB - Across taxa, males employ a variety of mating strategies, including sexual coercion and the provision, or trading, of resources. Biological market theory (BMT) predicts that trading of commodities for mating opportunities should exist only when males cannot monopolize access to females and/or obtain mating by force, in situations where power differentials between males are low; both coercion and trading have been reported for chimpanzees (Pan troglodytes). Here, we investigate whether the choice of strategy depends on the variation in male power differentials, using data from two wild communities of East African chimpanzees (Pan troglodytes schweinfurthii): the structurally despotic Sonso community (Budongo, Uganda) and the structurally egalitarian M-group (Mahale, Tanzania). We found evidence of sexual coercion by male Sonso chimpanzees, and of trading-of grooming for mating-by M-group males; females traded sex for neither meat nor protection from male aggression. Our results suggest that the despotism egalitarian axis influences strategy choice: male chimpanzees appear to pursue sexual coercion when power differentials are large and trading when power differentials are small and coercion consequently ineffective. Our findings demonstrate that trading and coercive strategies are not restricted to particular chimpanzee subspecies; instead, their occurrence is consistent with BMT predictions. Our study raises interesting, and as yet unanswered, questions regarding female chimpanzees' willingness to trade sex for grooming, if doing so represents a compromise to their fundamentally promiscuous mating strategy. It highlights the importance of within-species cross-group comparisons and the need for further study of the relationship between mating strategy and dominance steepness. PMID- 26279606 TI - Affect, Behavior, Cognition, and Desire in the Big Five: An Analysis of Item Content and Structure. AB - Personality psychology is concerned with affect (A), behavior (B), cognition (C) and desire (D), and personality traits have been defined conceptually as abstractions used to either explain or summarize coherent ABC (and sometimes D) patterns over time and space. However, this conceptual definition of traits has not been reflected in their operationalization, possibly resulting in theoretical and practical limitations to current trait inventories. Thus, the goal of this project was to determine the affective, behavioral, cognitive and desire (ABCD) components of Big-Five personality traits. The first study assessed the ABCD content of items measuring Big-Five traits in order to determine the ABCD composition of traits and identify items measuring relatively high amounts of only one ABCD content. The second study examined the correlational structure of scales constructed from items assessing ABCD content via a large, web-based study. An assessment of Big-Five traits that delineates ABCD components of each trait is presented, and the discussion focuses on how this assessment builds upon current approaches of assessing personality. PMID- 26279607 TI - Viral evolution and epidemiology. AB - This review highlights recent research on viral evolution and its use towards understanding disease pathogenesis and epidemiology. The development of techniques such as enzymatic amplification of viral genomes and automated sequencing has led to a dramatic increase in the amount of sequence information from clinical samples. These sequences (RNA or DNA, or the amino acids they encode) have been compared by complex computer algorithms to generate evolutionary trees or phylogenies of natural virus variants, which can sometimes be used to correlate viral genotype with phenotype. Understanding the rates and types of evolution that occur during the transmission of viruses has considerable impact on the design of methods for the control of virus diseases. PMID- 26279608 TI - Brain-Body Pathways Linking Psychological Stress and Physical Health. AB - Psychological stress is thought to arise from appraisal processes that ascribe threat-related meaning to experiences that tax or exceed our coping ability. Neuroimaging research indicates that these appraisal processes originate in brain systems that also control physiological stress reactions in the body. Separate lines of research in health psychology and behavioral medicine indicate that these physiological stress reactions confer risk for physical disease. Accordingly, integrative research that cuts across historically separated disciplines may help to define the brain-body pathways linking psychological stress to physical health. We describe recent studies aimed at this goal, focusing on studies of the brain bases of stressor-evoked cardiovascular system reactions and heart disease risk. We also outline an interpretive framework for these studies, as well as needs for next-generation models and metrics to better understand how the brain encodes and embodies stress in relation to health. PMID- 26279609 TI - Toward Defining, Measuring, and Evaluating LGBT Cultural Competence for Psychologists. AB - A central part of providing evidence-based practice is appropriate cultural competence to facilitate psychological assessment and intervention with diverse clients. At a minimum, cultural competence with lesbian, gay, bisexual, and transgender (LGBT) people involves adequate scientific and supervised practical training, with increasing depth and complexity across training levels. In order to further this goal, we offer 28 recommendations of minimum standards moving toward ideal training for LGBT-specific cultural competence. We review and synthesize the relevant literature to achieve and assess competence across the various levels of training (doctoral, internship, post-doctoral, and beyond) in order to guide the field towards best practices. These recommendations are aligned with educational and practice guidelines set forth by the field and informed by other allied professions in order to provide a roadmap for programs, faculty, and trainees in improving the training of psychologists to work with LGBT individuals. PMID- 26279610 TI - When they listen and when they watch: Pianists' use of nonverbal audio and visual cues during duet performance. AB - Nonverbal auditory and visual communication helps ensemble musicians predict each other's intentions and coordinate their actions. When structural characteristics of the music make predicting co-performers' intentions difficult (e.g., following long pauses or during ritardandi), reliance on incoming auditory and visual signals may change. This study tested whether attention to visual cues during piano-piano and piano-violin duet performance increases in such situations. Pianists performed the secondo part to three duets, synchronizing with recordings of violinists or pianists playing the primo parts. Secondos' access to incoming audio and visual signals and to their own auditory feedback was manipulated. Synchronization was most successful when primo audio was available, deteriorating when primo audio was removed and only cues from primo visual signals were available. Visual cues were used effectively following long pauses in the music, however, even in the absence of primo audio. Synchronization was unaffected by the removal of secondos' own auditory feedback. Differences were observed in how successfully piano-piano and piano-violin duos synchronized, but these effects of instrument pairing were not consistent across pieces. Pianists' success at synchronizing with violinists and other pianists is likely moderated by piece characteristics and individual differences in the clarity of cueing gestures used. PMID- 26279612 TI - Modified Dendrogram of High-dimensional Feature Space for Transfer Function Design. AB - We introduce a modified dendrogram (MD) (with sub-trees to represent the feature space clusters) and display it in continuous space for multi-dimensional transfer function (TF) design and modification. Such a TF for direct volume rendering often employs a multi-dimensional feature space. In an n-dimensional (nD) feature space, each voxel is described using n attributes and represented by a vector of n values. The MD reveals the hierarchical structure information of the high dimensional feature space clusters. Using the MD user interface (UI), the user can design and modify the TF in 2D in an intuitive and informative manner instead of designing it directly in multi-dimensional space where it is complicated and harder to understand the relationship of the feature space vectors. In addition, we provide the capability to interactively change the granularity of the MD. The coarse-grained MD shows primarily the global information of the feature space while the fine-grained MD reveals the finer details, and the separation ability of the high-dimensional feature space is completely preserved in the finest granularity. With the so called multi-grained method, the user can efficiently create a TF using the coarse-grained MD, then fine tune it with the finer-grained MDs to improve the quality of the volume rendering. Furthermore, we propose a fast interactive hierarchical clustering (FIHC) algorithm for accelerating the MD computation and supporting the interactive multi-grained TF design. In the FIHC, the finest-grained MD is established by linking the feature space vectors, then the feature space vectors being the leaves of this tree are clustered using a hierarchical leaf clustering (HLC) algorithm forming a leaf vector hierarchical tree (LVHT). The granularity of the MD can be changed by setting the precision of the LVHT. Our method is independent on the type of the attributes and supports arbitrary-dimension feature space. PMID- 26279611 TI - Income Generation in Recovering Heroin Users: A Comparative Analysis of Legal and Illegal Earnings. AB - Research has shown employment to be a central mediator to sustained recovery and community reentry for substance abusers; however, heroin users have lower employment rates and report lower mean incomes than other drug users. The authors of the present study assessed income generating behaviors of substance users recruited from substance abuse treatment facilities (N=247). Heroin users had higher mean incomes from illegal sources. Further, logistic regression analysis found heroin use to increase the likelihood of engagement in illegal income generating behaviors. As these results increase the likelihood of involvement in the criminal justice system, the implications for heroin specific treatment and rehabilitation are discussed. PMID- 26279613 TI - Conformal Magnifier: A Focus+Context Technique with Minimal Distortion. AB - We present the conformal magnifier, a novel interactive Focus+Context visualization technique to magnify a region of interest (ROI) using conformal mapping. Our framework allows the user to design an arbitrary magnifier to enlarge the features of interest while deforming part of the remaining areas without any cropping. By using conformal mapping, the ROI is magnified with minimal distortion, while the transition region is a smooth and continuous deformation between the focus and context regions. An interactive interface is designed for the user to select important features, design focus models of arbitrary shape and set deformation constraints to satisfy his/her specified requirements. We demonstrate the effectiveness, robustness and efficiency of our method using several applications: texts, maps, geographic images, data structures and multi-media visualization. PMID- 26279615 TI - Family Background, School-Age Trajectories of Activity Participation, and Academic Achievement at the Start of High School. AB - Applying latent class and regression techniques to data from the NICHD Study of Early Child Care and Youth Development (n = 997), this study explored the potential academic advantages of time spent in out-of-school activities. Of particular interest was how these potential advantages played out in relation to the timing and duration of activity participation and the family contexts in which it occurred. Participation closer to the start of high school-including consistent participants and latecomers-was associated with higher grades at the transition into high school, especially for youth from low-income families. Sensitivity analyses indicated that this link between school-age activity participation and adolescent academic progress was unlikely to be solely a function of selection. It also tended to be more pronounced among youth from lower-income families, although without varying by other aspects of family status or process. PMID- 26279614 TI - "Knowing That You're Not the Only One": Perspectives on Group-Based Cognitive Behavioral Therapy for Adherence and Depression (CBT-AD) in Adults With Type 1 Diabetes. AB - Depression and illness-specific distress are more common among adults with Type 1 diabetes (T1DM) than the general population and have been associated with poorer control of blood glucose and increased risk for serious diabetes-related complications. Treatment nonadherence has also been associated with depressive symptoms and diabetes-related distress, and has repeatedly been suggested as an important modifiable behavioral pathway linking depression and diabetes outcomes. The present study reports on the feasibility and acceptability of a pilot intervention using group-based cognitive-behavioral therapy to improve treatment adherence among adults with T1DM and elevated levels of diabetes-related distress or depressive symptoms. We describe the components of the intervention and utilize qualitative data along with descriptive outcome data. Our findings suggest that participation in the group was acceptable and associated with reductions in depressive symptoms and diabetes-specific distress. Challenges to feasibility and future directions are discussed. PMID- 26279616 TI - Class-Wide Function-Related Intervention Teams "CW-FIT" Efficacy Trial Outcomes. AB - The purpose of the study was to determine the efficacy of the Class-wide Function related Intervention Teams (CW-FIT) program for improving students' on-task behavior, and increasing teacher recognition of appropriate behavior. The intervention is a group contingency classroom management program consisting of teaching and reinforcing appropriate behaviors (i.e., getting the teacher's attention, following directions, and ignoring inappropriate behaviors of peers). Seventeen elementary schools, the majority in urban and culturally diverse communities, participated in a randomized trial with 86 teachers (classrooms) assigned to CW-FIT, and 73 teachers (classrooms) assigned to the comparison group. Class-wide student on-task behavior improved over baseline levels in the intervention classes. Teachers were able to implement the intervention with high fidelity overall, as observed in adherence to 96% of the fidelity criteria on average. Teacher praise and attention to appropriate behaviors increased, and reprimands decreased. These effects were replicated in new classrooms each of the 4 years of the study, and for all years combined. PMID- 26279617 TI - A Visualization Tool for Calculating the Genetic Substitution Patterns Between Two Different Groups. AB - We developed simulation tool for influenza virus variation (SimFluVar), an analytics software for calculating genomic variation among members of the influenza virus group. This study is related to computational evolutionary biology and evolutionary bioinformatics. SimFluVar is an analytical tool that can be used to calculate codon substitution patterns of viral genes. Designed to compare a large number of nucleotide sequences, SimFluVar provides precise patterns of codon variations between two viral groups, especially for the influenza virus. SimFluVar also provides useful functions, such as editing and visualization of the result matrix. This new tool can be used to analyze codon variation patterns over time as well as to analyze the genomic differences between viruses obtained from different geographical locations. SimFluVar is developed in C++, and Java RCP is used as a distribution package. SimFluVar, including the associated documentation, manuals, and examples, is publicly available at http://lcbb.snu.ac.kr/simfluvar. PMID- 26279618 TI - A Single-Array-Based Method for Detecting Copy Number Variants Using Affymetrix High Density SNP Arrays and its Application to Breast Cancer. AB - Cumulative evidence has shown that structural variations, due to insertions, deletions, and inversions of DNA, may contribute considerably to the development of complex human diseases, such as breast cancer. High-throughput genotyping technologies, such as Affymetrix high density single-nucleotide polymorphism (SNP) arrays, have produced large amounts of genetic data for genome-wide SNP genotype calling and copy number estimation. Meanwhile, there is a great need for accurate and efficient statistical methods to detect copy number variants. In this article, we introduce a hidden-Markov-model (HMM)-based method, referred to as the PICR-CNV, for copy number inference. The proposed method first estimates copy number abundance for each single SNP on a single array based on the raw fluorescence values, and then standardizes the estimated copy number abundance to achieve equal footing among multiple arrays. This method requires no between array normalization, and thus, maintains data integrity and independence of samples among individual subjects. In addition to our efforts to apply new statistical technology to raw fluorescence values, the HMM has been applied to the standardized copy number abundance in order to reduce experimental noise. Through simulations, we show our refined method is able to infer copy number variants accurately. Application of the proposed method to a breast cancer dataset helps to identify genomic regions significantly associated with the disease. PMID- 26279619 TI - Secondary Data Analytics of Aquaporin Expression Levels in Glioblastoma Stem-Like Cells. AB - Glioblastoma is the most common brain tumor in adults in which recurrence has been attributed to the presence of cancer stem cells in a hypoxic microenvironment. On the basis of tumor formation in vivo and growth type in vitro, two published microarray gene expression profiling studies grouped nine glioblastoma stem-like (GS) cell lines into one of two groups: full (GSf) or restricted (GSr) stem-like phenotypes. Aquaporin-1 (AQP1) and aquaporin-4 (AQP4) are water transport proteins that are highly expressed in primary glial-derived tumors. However, the expression levels of AQP1 and AQP4 have not been previously described in a panel of 92 glioma samples. Therefore, we designed secondary data analytics methods to determine the expression levels of AQP1 and AQP4 in GS cell lines and glioblastoma neurospheres. Our investigation also included a total of 2,566 expression levels from 28 Affymetrix microarray probe sets encoding 13 human aquaporins (AQP0-AQP12); CXCR4 (the receptor for stromal cell derived factor-1 [SDF-1], a potential glioma stem cell therapeutic target]); and PROM1 (gene encoding CD133, the widely used glioma stem cell marker). Interactive visual representation designs for integrating phenotypic features and expression levels revealed that inverse expression levels of AQP1 and AQP4 correlate with distinct phenotypes in a set of cell lines grouped into full and restricted stem like phenotypes. Discriminant function analysis further revealed that AQP1 and AQP4 expression are better predictors for tumor formation and growth types in glioblastoma stem-like cells than are CXCR4 and PROM1. Future investigations are needed to characterize the molecular mechanisms for inverse expression levels of AQP1 and AQP4 in the glioblastoma stem-like neurospheres. PMID- 26279620 TI - Applications of iPSCs in Cancer Research. AB - Induced pluripotent stem cells (iPSCs) derived from reprogrammed somatic cells are emerging as one of the most versatile tools in biomedical research and pharmacological studies. Oncogenic transformation and somatic cell reprogramming are multistep processes that share some common features, and iPSCs generated from cancerous cells can help us better understand the molecular mechanisms underlying the initiation and progression of human cancers and overcome them. Aside from the mechanistic modeling of human tumorigenesis, immediate applications of this technology in cancer research include high-throughput drug screening, toxicological testing, early biomarker identification, and bioengineering of replacement tissues. Here, we review the current advances in generating iPSCs from cancer cell lines and patient-derived primary cancer tissues, and discuss their potential applications. PMID- 26279621 TI - Spectrophotometric Determination of Cefixime Trihydrate in Pharmaceutical Formulations Based on Ion-Pair Reaction with Bromophenol Blue. AB - Cefixime trihydrate is a broad spectrum cephalosporin antibiotic, effective against gram-positive and gram-negative bacterial infections. Simple and rapid method has been developed for the determination of cefixime trihydrate in bulk and pharmaceutical formulations. This method was based on the formation of bluish green ion-pair complex of cefixime trihydrate with bromophenol blue in dimethyl sulfoxide (DMSO)-acetonitrile medium. Different parameters were studied and optimized. A 2:1 complex was formed between the drug and reagent almost instantaneously at room temperature which has lambdamax of 610 nm. Under optimum conditions, calibration curve was found to be linear over the range of 10-130 MUg mL(-1). The method was subjected to analytical quality control. The limit of detection was found to be 1.08 MUg mL(-1). Recovery studies and interference studies were carried out. The proposed method was successfully applied to the determination of cefixime trihydrate in bulk and pharmaceutical formulations with high precision and accuracy. PMID- 26279622 TI - Correction to "Safety and Efficacy of Gadobutrol for Contrast-enhanced Magnetic Resonance Imaging of the Central Nervous System: Results from a Multicenter, Double-blind, Randomized, Comparator Study". PMID- 26279623 TI - Single Nucleotide Polymorphisms Caused by Assembly Errors. AB - We compare the results of three different assembler programs, Celera, Phrap and Mira2, for the same set of about a hundred thousand Sanger reads derived from an unknown bacterial genome. In difference to previous assembly comparisons we do not focus on speed of computation and numbers of assembled contigs but on how the different sequence assemblies agree by content. Threefold consistently assembled genome regions are identified in order to estimate a lower bound of erroneously identified single nucleotide polymorphisms (SNP) caused by nothing but the process of mathematical sequence assembly. We identified 509 sequence triplets common to all three de-novo assemblies spanning only 34% (3.3 Mb) of the bacterial genome with 175 of these regions (~1.5 Mb) including erroneous SNPs and insertion/deletions. Within these triplets this on average leads to one error per 7,155 base pairs. Replacing the assembler Mira2 by the most recent version Mira3, the letter number even drops to 5,923. Our results therefore suggest that a considerably high number of erroneous SNPs may be present in current sequence data and mathematicians should urgently take up research on numerical stability of sequence assembly algorithms. Furthermore, even the latest versions of currently used assemblers produce erroneous SNPs that depend on the order reads are used as input. Such errors will severely hamper molecular diagnostics as well as relating genome variation and disease. This issue needs to be addressed urgently as the field is moving fast into clinical applications. PMID- 26279624 TI - Design, Construction and Validation of Targeted BAC Array-Based CGH Test for Detecting the Most Commons Chromosomal Abnormalities. AB - We designed a targeted-array called GOLD (Gain or Loss Detection) Chip consisting of 900 FISH-mapped non-overlapping BAC clones spanning the whole genome to enhance the coverage of 66 unique human genomic regions involved in well known microdeletion/microduplication syndromes. The array has a 10 Mb backbone to guarantee the detection of the aneuploidies, and has an implemented resolution for telomeres, and for regions involved in common genomic diseases. In order to evaluate clinical diagnostic applicability of GOLDChip, analytical validity was carried-out via retrospective analysis of DNA isolated from a series of cytogenetically normal amniocytes and cytogenetically abnormal DNA obtained from cultured amniocytes, peripheral blood and/or cell lines. We recruited 47 DNA samples corresponding to pathologies with significant frequencies (Cri du Chat syndrome, Williams syndrome, Prader Willi/Angelman syndromes, Smith-Magenis syndrome, DiGeorge syndrome, Miller-Dieker syndrome, chromosomes 13, 18 and 21 trisomies). We set up an experimental protocol that allowed to identify chromosomal rearrangements in all the DNA samples analyzed. Our results provide evidence that our targeted BAC array can be used for the identification of the most common microdeletion syndromes and common aneuploidies. PMID- 26279625 TI - Efficacy of Single-stage Revision with Aggressive Debridement Using Intra articular Antibiotics in the Treatment of Infected Joint Prosthesis. AB - Prosthetic joint infections (PJI) of the hip and knee are uncommon, but result in significant morbidity and mortality when they do occur. Current management consists of a combination of either single- or two-stage exchange of the prosthesis and/or exchange of polymer components with intravenous (IV) antibiotics (4-6 weeks) and intraoperative debridement of the joint prior to reimplantation. However, failure rate, morbidity, and expense associated with current management are high, especially if the infection involves resistant pathogens and/or osteomyelitis. Also, the current use of systemic antibiotics does not allow for high local concentrations of the drug and biofilm penetration of the infected prosthesis. To overcome these difficulties, we examined the outcomes of aggressive operative debridement of the infected prosthesis. This was achieved through the use of a single-stage revision and administration of high concentrations of local intra-articular antibiotics via Hickman catheters. We present 57 patients with PJI who were treated with intra-articular antibiotics and single-stage revisions. Minimal systemic toxicity was observed along with a 100% microbiologic cure rate and 89% without relapse at 11-month follow-up despite isolation of multidrug resistant pathogens. This is the largest study to date using this method in the treatment of PJI. PMID- 26279626 TI - DNA Sequence Signatures for Rapid Detection of Six Target Bacterial Pathogens Using PCR Assays. AB - Using Streptococcus pyogenes as a model, we previously established a stepwise computational workflow to effectively identify species-specific DNA signatures that could be used as PCR primer sets to detect target bacteria with high specificity and sensitivity. In this study, we extended the workflow for the rapid development of PCR assays targeting Enterococcus faecalis, Enterococcus faecium, Clostridium perfringens, Clostridium difficile, Clostridium tetani, and Staphylococcus aureus, which are of safety concern for human tissue intended for transplantation. Twenty-one primer sets that had sensitivity of detecting 5-50 fg DNA from target bacteria with high specificity were selected. These selected primer sets can be used in a PCR array for detecting target bacteria with high sensitivity and specificity. The workflow could be widely applicable for the rapid development of PCR-based assays for a wide range of target bacteria, including those of biothreat agents. PMID- 26279627 TI - Molecular Heterogeneity in Primary Breast Carcinomas and Axillary Lymph Node Metastases Assessed by Genomic Fingerprinting Analysis. AB - Molecular heterogeneity within primary breast carcinomas and among axillary lymph node (LN) metastases may impact diagnosis and confound treatment. In this study, we used short tandem repeated sequences to assess genomic heterogeneity and to determine hereditary relationships among primary tumor areas and regional metastases from 30 breast cancer patients. We found that primary carcinomas were genetically heterogeneous and sampling multiple areas was necessary to adequately assess genomic variability. LN metastases appeared to originate at different time periods during disease progression from different sites of the primary tumor and the extent of genomic divergence among regional metastases was associated with a less favorable patient outcome (P = 0.009). In conclusion, metastasis is a complex process influenced by primary tumor heterogeneity and variability in the timing of dissemination. Genomic variation in primary breast tumors and regional metastases may negatively impact clinical diagnostics and contribute to therapeutic resistance. PMID- 26279629 TI - New Insight on the Role of Plasminogen Receptor in Cancer Progression. AB - OBJECTIVE: Plasminogen system plays a crucial role in physiological and pathological events related to tissue regeneration, wound healing, immune response, angiogenesis, invasion and metastasis. It gets activated when plasminogen associates with its cell surface receptors. Latest information on some of the well-explored plasminogen receptors such as annexin II-S100A10, cytokeratin 8, alpha-enolase, plasminogen receptor (KT) (Plg-R(KT)) and histone H2B has been discussed in the present review. These receptors can pave the way for effective new therapeutic and diagnostic strategies to counteract malignant diseases. CONCLUSION: The present review concludes the key role of plasminogen receptors in extracellular matrix degradation, infiltration into surrounding tissues, neovascularization, invasion, metastasis and drug resistance. This review also discusses the possible effect of blocking these plasminogen receptors with monoclonal antibodies and DNA-based vaccination or silencing plasminogen receptor gene using small interfering RNA or short hairpin RNA to counteract cancer invasion and metastasis. PMID- 26279630 TI - Are Motor Skills and Motor Inhibitions Impaired in Tourette Syndrome? A Review. AB - Tourette syndrome (TS) is a neurodevelopmental motor disorder described as an inability to inhibit unwanted motor movements. This article reviews research on the execution and inhibition of voluntary motor movements in TS. Over last two decades, a number of studies have addressed the structural and functional deficits associated with this syndrome. Only a limited number of studies have assessed the motor skills in these patients but have failed to reach any conclusive outcome. In the domain of response inhibition also, studies have reported arguable impairments in these patients. It is suggested that these conflicting results can be attributed to co-occurring comorbid conditions, the constraints posed by variable age groups, lack of control measures, and lack of specificity of domains addressed. This review will describe a way in which future research can be directed to increase our knowledge of this otherwise complex spectrum of disorders. PMID- 26279628 TI - Pattern Recognition Receptors in Cancer Progression and Metastasis. AB - The innate immune system is an integral component of the inflammatory response to pathophysiological stimuli. Toll-like receptors (TLRs) and inflammasomes are the major sensors and pattern recognition receptors (PRRs) of the innate immune system that activate stimulus (signal)-specific pro-inflammatory responses. Chronic activation of PRRs has been found to be associated with the aggressiveness of various cancers and poor prognosis. Involvement of PRRs was earlier considered to be limited to infection- and injury-driven carcinogenesis, where they are activated by pathogenic ligands. With the recognition of damage associated molecular patterns (DAMPs) as ligands of PRRs, the role of PRRs in carcinogenesis has also been implicated in other non-pathogen-driven neoplasms. Dying (apoptotic or necrotic) cells shed a plethora of DAMPs causing persistent activation of PRRs, leading to chronic inflammation and carcinogenesis. Such chronic activation of TLRs promotes tumor cell proliferation and enhances tumor cell invasion and metastasis by regulating pro-inflammatory cytokines, metalloproteinases, and integrins. Due to the decisive role of PRRs in carcinogenesis, targeting PRRs appears to be an effective cancer-preventive strategy. This review provides a brief account on the association of PRRs with various cancers and their role in carcinogenesis. PMID- 26279631 TI - Safety and Feasibility of a KineSpring Knee System for the Treatment of Osteoarthritis: A Case Series. AB - The treatment gap between conservative management and total knee arthroplasty may leave patients with moderate cases of knee osteoarthritis (OA) without an ideal treatment option. The KineSpring((r)) Knee Implant System may be a viable treatment option to fill the treatment gap for patients with knee OA who are not willing or inappropriate candidates for total knee arthroplasty, yet do not demonstrate relief with conservative treatments. This current paper reports a series of patients who received the KineSpring System and were followed for five years. Twelve patients were included in the case series. All 12 patients were diagnosed with symptomatic OA of the medial compartment of the knee. Pain and functional problems associated with OA improved with treatment using the KineSpring System. Furthermore, these improvements were seen over the course of five years. The findings of this study show the KineSpring System as a promising intervention for early-onset OA and warrant further investigation regarding its effectiveness. PMID- 26279632 TI - Dasatinib Induced Avascular Necrosis of Femoral Head in Adult Patient with Chronic Myeloid Leukemia. AB - Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of the Philadelphia (Ph) chromosome resulting from the reciprocal translocation t(9;22)(q34;q11). The molecular consequence of this translocation is the generation of the BCR-ABL fusion gene, which encodes a constitutively active protein tyrosine kinase. The oncogenic protein tyrosine kinase, which is located in the cytoplasm, is responsible for the leukemia phenotype through the constitutive activation of multiple signaling pathways involved in the cell cycle and in adhesion and apoptosis. Avascular necrosis of the femoral head (AVNFH) is not a specific disease. It occurs as a complication or secondary to various causes. These conditions probably lead to impaired blood supply to the femoral head. The diagnosis of AVNFH is based on clinical findings and is supported by specific radiological manifestations. We reported a case of a 34-year-old Sudanese female with CML who developed AVNFH after receiving dasatinib as a second-line therapy. Though the mechanism by which dasatinib can cause avascular necrosis (AVN) is not clear, it can be postulated because of microcirculatory obstruction of the femoral head. To the best of our knowledge and after extensive literature search, this is the first reported case of AVNFH induced by dasatinib in a patient with CML. PMID- 26279633 TI - Anti-Inflammatory Diet for Atherosclerosis and Coronary Artery Disease: Antioxidant Foods. AB - Oxidative stress plays a role in atherosclerotic diseases such as coronary artery disease (CAD), and much attention has been paid to antioxidant foods. The relationships between the consumption of vegetables and fruits and atherosclerotic diseases have been reported in many epidemiological studies showing a reduced risk of such diseases. In addition to the antioxidant vitamins C and E, green and yellow vegetables contain abundant quantities of carotenoids and polyphenols. The consumption of carotenoids and vitamins C and E has been shown to be inversely associated with CAD. However, supplementation with beta carotene and vitamins C and E shows no beneficial effect, but rather mortality is increased with beta-carotene and vitamin E supplements. Therefore, it is recommended to consume vegetables and fruits, but vitamin supplementation is not recommended. Many epidemiological studies also report that higher consumption of fish, rich in n-3 polyunsaturated fatty acids (PUFAs), is associated with a lower risk of CAD and stroke. Antiatherosclerotic effects of n-3 PUFAs include reduced platelet aggregation, triglyceride-lowering effect, anti-inflammatory effect, and plaque stabilization, but the anti-inflammatory effect is principally responsible for preventing atherosclerosis. It is recommended to consume fish at least twice a week in patients without CAD and to consider n-3 PUFA supplements in patients with documented CAD. Regarding soy products, soy protein consumption reduces low density-lipoprotein cholesterol and triglyceride levels. Isoflavone, a polyphenol contained in soybeans, has antiatherosclerotic property because it has a structure similar to that of estrogen and bonds with estrogen receptors. High consumption of isoflavone has been reported to be associated with a reduced risk of CAD and stroke only in women, but the preventative effect of soy products in the general population has not yet been clarified. Thus, many epidemiological studies report the promising effects of antioxidant foods, but there are many unclear points remaining with regard to the contribution of the nutritional elements found in antioxidant foods to the prevention of atherosclerotic diseases. PMID- 26279634 TI - An International Observational Prospective Survey Assessing the Control of Atrial Fibrillation in Asia-Pacific: Results of the Record-AFAP Registry. AB - A prospective 1-year observational survey was designed to assess the management and control of atrial fibrillation (AF) in eight countries within the Asia Pacific region. Patients (N = 2,604) with recently diagnosed AF or a history of AF <=1 year were included. Clinicians chose the treatment strategy (rhythm or rate control) according to their standard practice and medical discretion. The primary endpoint was therapeutic success. At baseline, rhythm- and rate-control strategies were applied to 35.7% and 64.3% of patients, respectively. At 12 months, therapeutic success was 43.2% overall. Being assigned to rhythm-control strategy at baseline was associated with a higher therapeutic success (46.5% vs 41.4%; P = 0.0214) and a lower incidence of clinical outcomes (10.4% vs 17.1% P < 0.0001). Patients assigned to rate-control strategies at baseline had higher cardiovascular morbidities (history of heart failure or valvular heart disease). Cardiovascular outcomes may be less dependent on the choice of treatment strategy than cardiovascular comorbidities. PMID- 26279635 TI - Accidental Rivaroxaban Overdose in a Patient with Pulmonary Embolism: Some Lessons for Managing New Oral Anticoagulants. AB - Rivaroxaban is an orally active direct factor Xa inhibitor used to treat venous thromboembolism with approved starting dose of 15 mg twice-daily. We present a case of an accidental overdose in a patient with pulmonary thromboembolism, when the patient received two 150 mg doses of rivaroxaban, instead of 15 mg as prescribed, given 12 hours apart. This error was recognised ten minutes after the second dose, when 50 gm oral activated charcoal was given. Rivaroxaban was stopped and rivaroxaban concentrations, INR, and APTT were monitored. The overdose was uncomplicated and 15 mg twice-daily rivaroxaban was restarted on day two. Apparently unlikely and potentially hazardous dispensing errors do happen. Each oral anticoagulant has a different dosing schedule. In our patient, the prescription for 15 mg twice-daily rivaroxaban was misread as 150 mg twice-daily (a correct dose for dabigatran in atrial fibrillation). Such errors are preventable. Prompt administration of activated charcoal under monitoring of a specific rivaroxaban assay can greatly help management of unusual situations like this one. PMID- 26279637 TI - Treatment of Myasthenia Gravis in Patients with Elderly Onset at Advanced Age. AB - The number of patients with late-onset myasthenia gravis (MG) among patients >=50 years has been increasing recently. We encountered three patients who developed elderly-onset MG at a particularly advanced age (>=80 years). All were female and positive for anti-acetylcholine receptor antibodies. About 4 years have passed since MG onset in all three patients and symptoms have been controlled without recurrence using a combination of oral low-dose prednisolone and tacrolimus. As many cases of elderly-onset MG do not require strong immunosuppression, we recommend minimum immunosuppressive treatment to avoid adverse events, particularly in patients at an advanced age of >=80 years. PMID- 26279636 TI - Recent Treatment of Interstitial Lung Disease with Idiopathic Inflammatory Myopathies. AB - Interstitial lung disease (ILD) is a prognostic factor for poor outcome in polymyositis (PM)/dermatomyositis (DM). The appropriate management of ILD is very important to improve the prognosis of patients with PM/DM. ILD activity and severity depend on the disease subtype. Therefore, clinicians should determine therapeutic strategies according to the disease subtype in each patient with PM/DM. Anti-melanoma differentiation-associated gene 5 antibody and hyperferritinemia predict the development and severity of rapidly progressive (RP) ILD, particularly in East Asian patients. Combination therapy with corticosteroids, intravenous cyclophosphamide pulse, and calcineurin inhibitors should be administered in RP-ILD. In contrast, patients with anti-aminoacyl-tRNA synthetase (ARS) show better responses to corticosteroids alone. However, ILDs with anti-ARS often display disease recurrence or become refractory to corticosteroid monotherapy. Recent studies have demonstrated that the administration of tacrolimus or rituximab in addition to corticosteroids may be considered in ILD patients with anti-ARS. Large-scale, multicenter randomized clinical trials should be conducted in the future to confirm that the aforementioned agents exhibit efficacy in ILD patients with PM/DM. The pathophysiology of ILD with PM/DM should also be elucidated in greater detail to develop effective therapeutic strategies for patients with ILD in PM/DM. PMID- 26279638 TI - Coordinating Chiral Ionic Liquids: Design, Synthesis, and Application in Asymmetric Transfer Hydrogenation under Aqueous Conditions. AB - Hydrophilic coordinating chiral ionic liquids with an amino alcohol substructure were developed and efficiently applied to the asymmetric reduction of ketones. Their careful design and adaptability to the desired reaction conditions allow for these chiral ionic liquids to be used as the sole source of chirality in a ruthenium-catalyzed transfer hydrogenation reaction of aromatic ketones. When used in this reaction system, these chiral ionic liquids afforded excellent yields and high enantioselectivities. PMID- 26279639 TI - Effects of the aqueous extract of a Tibetan herb, Rhodiola algida var. tangutica on proliferation and HIF-1alpha, HIF-2alpha expression in MCF-7 cells under hypoxic condition in vitro. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Rhodiola algida var. tangutica is a traditional Tibetan herb. Its root and rhizome have been successfully used as an effective clinical remedy for the prevention and treatment of cancer and high-altitude sickness. This study aimed to investigate the effect of Rhodiola algida var. tangutica on hypoxic MCF-7 breast cancer cells and the underlying mechanisms. MATERIALS AND METHODS: The antiproliferative effects of R. algida on MCF-7 breast cancer cells were compared in vitro under hypoxic and normal conditions by using MTT analysis. The influence of R. algida on cancer cell apoptosis was determined by flow cytometry. The expression levels of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha were evaluated by western blot analysis. RESULTS: R. algida inhibited the proliferation of MCF-7 breast cancer cells in a dose- and time dependent manner. The results of flow cytometry indicated that the antiproliferative effect of R. algida was mediated by apoptosis induction. Pretreatment with R. algida significantly suppressed the hypoxia-induced proliferation and expression of HIF-1alpha and HIF-2alpha in MCF-7 breast cancer cells. CONCLUSIONS: R. algida might exert an anti-carcinogenic effect on MCF-7 breast cancer cells by decreasing the protein levels of HIF-1alpha and HIF 2alpha, which are overexpressed under hypoxic conditions. This effect might be elicited by inhibiting the hypoxia-induced proliferation of MCF-7 breast cancer cells. PMID- 26279640 TI - Proteome analysis of shell matrix proteins in the brachiopod Laqueus rubellus. AB - BACKGROUND: The calcitic brachipod shells contain proteins that play pivotal roles in shell formation and are important in understanding the evolution of biomineralization. Here, we performed a large-scale exploration of shell matrix proteins in the brachiopod Laqueus rubellus. RESULTS: A total of 40 proteins from the shell were identified. Apart from five proteins, i.e., ICP-1, MSP130, a cysteine protease, a superoxide dismutase, and actin, all other proteins identified had no homologues in public databases. Among these unknown proteins, one shell matrix protein was identified with a domain architecture that includes a NAD(P) binding domain, an ABC-type transport system, a transmembrane region, and an aspartic acid rich region, which has not been detected in other biominerals. We also identified pectin lyase-like, trypsin inhibitor, and saposin B functional domains in the amino acid sequences of the shell matrix proteins. The repertoire of brachiopod shell matrix proteins also contains two basic amino acid-rich proteins and proteins that have a variety of repeat sequences. CONCLUSIONS: Our study suggests an independent origin and unique mechanisms for brachiopod shell formation. PMID- 26279641 TI - Psychotherapy for Bipolar Disorder in Adults: A Review of the Evidence. AB - Although pharmacotherapy is the mainstay of treatment for bipolar disorder, medication offers only partial relief for patients. Treatment with pharmacologic interventions alone is associated with disappointingly low rates of remission, high rates of recurrence, residual symptoms, and psychosocial impairment. Bipolar specific therapy is increasingly recommended as an essential component of illness management. This review summarizes the available data on psychotherapy for adults with bipolar disorder. We conducted a search of the literature for outcome studies published between 1995 and 2013 and identified 35 reports of 28 randomized controlled trials testing individual or group psychosocial interventions for adults with bipolar disorder. These reports include systematic trials investigating the efficacy and effectiveness of individual psychoeducation, group psychoeducation, individual cognitive-behavioral therapy, group cognitive-behavioral therapy, family therapy, interpersonal and social rhythm therapy, and integrated care management. The evidence demonstrates that bipolar disorder-specific psychotherapies, when added to medication for the treatment of bipolar disorder, consistently show advantages over medication alone on measures of symptom burden and risk of relapse. Whether delivered in a group or individual format, those who receive bipolar disorder-specific psychotherapy fare better than those who do not. Psychotherapeutic strategies common to most bipolar disorder-specific interventions are identified. PMID- 26279642 TI - Asymptotically Optimal Motion Planning for Learned Tasks Using Time-Dependent Cost Maps. AB - : In unstructured environments in people's homes and workspaces, robots executing a task may need to avoid obstacles while satisfying task motion constraints, e.g., keeping a plate of food level to avoid spills or properly orienting a finger to push a button. We introduce a sampling-based method for computing motion plans that are collision-free and minimize a cost metric that encodes task motion constraints. Our time-dependent cost metric, learned from a set of demonstrations, encodes features of a task's motion that are consistent across the demonstrations and, hence, are likely required to successfully execute the task. Our sampling-based motion planner uses the learned cost metric to compute plans that simultaneously avoid obstacles and satisfy task constraints. The motion planner is asymptotically optimal and minimizes the Mahalanobis distance between the planned trajectory and the distribution of demonstrations in a feature space parameterized by the locations of task-relevant objects. The motion planner also leverages the distribution of the demonstrations to significantly reduce plan computation time. We demonstrate the method's effectiveness and speed using a small humanoid robot performing tasks requiring both obstacle avoidance and satisfaction of learned task constraints. NOTE TO PRACTITIONERS: Motivated by the desire to enable robots to autonomously operate in cluttered home and workplace environments, this paper presents an approach for intuitively training a robot in a manner that enables it to repeat the task in novel scenarios and in the presence of unforeseen obstacles in the environment. Based on user-provided demonstrations of the task, our method learns features of the task that are consistent across the demonstrations and that we expect should be repeated by the robot when performing the task. We next present an efficient algorithm for planning robot motions to perform the task based on the learned features while avoiding obstacles. We demonstrate the effectiveness of our motion planner for scenarios requiring transferring a powder and pushing a button in environments with obstacles, and we plan to extend our results to more complex tasks in the future. PMID- 26279645 TI - High-Frequency Replanning Under Uncertainty Using Parallel Sampling-Based Motion Planning. AB - As sampling-based motion planners become faster, they can be re-executed more frequently by a robot during task execution to react to uncertainty in robot motion, obstacle motion, sensing noise, and uncertainty in the robot's kinematic model. We investigate and analyze high-frequency replanning (HFR), where, during each period, fast sampling-based motion planners are executed in parallel as the robot simultaneously executes the first action of the best motion plan from the previous period. We consider discrete-time systems with stochastic nonlinear (but linearizable) dynamics and observation models with noise drawn from zero mean Gaussian distributions. The objective is to maximize the probability of success (i.e., avoid collision with obstacles and reach the goal) or to minimize path length subject to a lower bound on the probability of success. We show that, as parallel computation power increases, HFR offers asymptotic optimality for these objectives during each period for goal-oriented problems. We then demonstrate the effectiveness of HFR for holonomic and nonholonomic robots including car-like vehicles and steerable medical needles. PMID- 26279644 TI - Effects of oral phosphatidic acid feeding with or without whey protein on muscle protein synthesis and anabolic signaling in rodent skeletal muscle. AB - BACKGROUND: Phosphatidic acid (PA) is a diacyl-glycerophospholipid that acts as a signaling molecule in numerous cellular processes. Recently, PA has been proposed to stimulate skeletal muscle protein accretion, but mechanistic studies are lacking. Furthermore, it is unknown whether co-ingesting PA with other leucine containing ingredients can enhance intramuscular anabolic signaling mechanisms. Thus, the purpose of this study was to examine if oral PA feeding acutely increases anabolic signaling markers and muscle protein synthesis (MPS) in gastrocnemius with and without whey protein concentrate (WPC). METHODS: Overnight fasted male Wistar rats (~250 g) were randomly assigned to four groups: control (CON, n = 6-13), PA (29 mg; n = 8), WPC (197 mg; n = 8), or PA + WPC (n = 8). Three hours post-feeding, gastrocnemius muscle was removed for markers of Akt mTOR signaling, gene expression patterns related to skeletal muscle mass regulation and metabolism, and MPS analysis via the SUnSET method. RESULTS: Compared to CON rats, PA, WPC and PA + WPC resulted in a significant elevation in the phosphorylation of mTOR (Ser2481) and rps6 (Ser235/236) (p < 0.05) in the gastrocnemius though there were no differences between the supplemented groups. MPS levels in the gastrocnemius were significantly (p < 0.05) elevated in WPC versus CON rats, and tended to be elevated in PA versus CON rats (p = 0.08), though MPS was less in PA + WPC versus WPC rats (p < 0.05) in spite of robust increases in mTOR pathway activity markers in the former group. C2C12 myoblast data agreed with the in vivo data herein showing that PA increased MPS levels 51% (p < 0.001) phosphorylated p70s6k (Thr389) levels 67% (p < 0.001). CONCLUSIONS: Our results are the first in vivo evidence to demonstrate that PA tends to increases MPS 3 h post-feeding, though PA may delay WPC-mediated MPS kinetics within a 3 h post-feeding window. PMID- 26279643 TI - PEYRONIE'S DISEASE: A REVIEW OF ETIOLOGY, DIAGNOSIS, AND MANAGEMENT. AB - Peyronie's Disease (PD) is a superficial fibrosing disorder of the penis resulting in plaque formation and penile deformity. Once considered rare, PD has more recently been found in up to 13% of men, and can negatively affect sexual and psychosocial function of both patients and their partners. While the etiology of PD is unclear, it is thought to result from an inciting traumatic event followed by aberrant fibrosis or dysregulated wound healing. The evaluation of men presenting with PD includes a detailed history and physical exam, focusing on the penis in both the flaccid and erect states. PD is often associated with erectile dysfunction (ED), as well as several other comorbidities. Laboratory testing is not needed to diagnose PD, although given the associations between PD and systemic diseases including hypogonadism, diabetes, and cardiovascular disease, screening and work-up for these conditions in men with PD may be warranted. Treatment modalities for PD are diverse and include oral, topical, intralesional, mechanical, and surgical therapies. Oral, topical, and mechanical therapies generally have little evidence supporting their efficacy. Several intralesional therapies, including interferon alpha2b and collagenase Clostridium hystiolyticum have demonstrated efficacy in the treatment of PD. Surgical treatment, indicated in men with significant, stable deformity, includes plication of the tunica albuginea, plaque incision/excision and grafting, and placement of inflatable penile prosthesis (IPP) with or without additional maneuvers to achieve desired results, and has high success rates. PMID- 26279646 TI - Acute behavioral interventions and outpatient treatment strategies with suicidal adolescents. AB - Despite the prevalence of suicidal thoughts and behaviors among adolescents, there is limited knowledge of effective interventions to use with this population. This paper reviews the findings of studies on behavioral interventions for adolescents who are at acute suicide risk, as well as outpatient treatment and risk management strategies with suicidal adolescents. The importance of addressing comorbid behaviors and enhancing protective factors are discussed. Cultural considerations in working with suicidal adolescents and strategies for conducting culturally competent treatment are explored. PMID- 26279648 TI - Gene Fusion due to Chromosome Misconnection May Seriously Affect Your Health. PMID- 26279649 TI - MAN1B1 Mutation Leads to a Recognizable Phenotype: A Case Report and Future Prospects. AB - Intellectual disability (ID) is one of the most common reasons for referral to genetic counseling. Nevertheless, in over 50% of the cases no diagnosis can be made. Here, we present how exome sequencing in combination with medical genetics evaluation led to the identification of a known pathogenic homozygous mutation in MAN1B1 in a consanguineous Turkish family. The phenotype comprised mild ID, truncal obesity and facial dysmorphism, comparable to that of the patients in the 3 recent publications on mutations in this gene. Clinically, the majority of patients in the literature showed congenital disorder of glycosylation syndrome type 2. In this study, we summarize the current knowledge about MAN1B1 mutations from the literature as well as databases and suggest that exome sequencing should be implemented in a larger scale in routine diagnostics, since autosomal recessive ID has proven to be extremely heterogeneous. Even syndromic patterns may only become recognizable retrospectively. PMID- 26279647 TI - Blood-based lung cancer biomarkers identified through proteomic discovery in cancer tissues, cell lines and conditioned medium. AB - BACKGROUND: Support for early detection of lung cancer has emerged from the National Lung Screening Trial (NLST), in which low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20 % relative to chest x-ray. The US Preventive Services Task Force (USPSTF) recently recommended annual screening for the high-risk population, concluding that the benefits (life years gained) outweighed harms (false positive findings, abortive biopsy/surgery, radiation exposure). In making their recommendation, the USPSTF noted that the moderate net benefit of screening was dependent on the resolution of most false positive results without invasive procedures. Circulating biomarkers may serve as a valuable adjunctive tool to imaging. RESULTS: We developed a broad-based proteomics discovery program, integrating liquid chromatography/mass spectrometry (LC/MS) analyses of freshly resected lung tumor specimens (n = 13), lung cancer cell lines (n = 17), and conditioned media collected from tumor cell lines (n = 7). To enrich for biomarkers likely to be found at elevated levels in the peripheral circulation of lung cancer patients, proteins were prioritized based on predicted subcellular localization (secreted, cell-membrane associated) and differential expression in disease samples. 179 candidate biomarkers were identified. Several markers selected for further validation showed elevated levels in serum collected from subjects with stage I NSCLC (n = 94), relative to healthy smoker controls (n = 189). An 8-marker model was developed (TFPI, MDK, OPN, MMP2, TIMP1, CEA, CYFRA 21-1, SCC) which accurately distinguished subjects with lung cancer (n = 50) from high risk smokers (n = 50) in an independent validation study (AUC = 0.775). CONCLUSIONS: Integrating biomarker discovery from multiple sample types (fresh tissue, cell lines and conditioned medium) has resulted in a diverse repertoire of candidate biomarkers. This unique collection of biomarkers may have clinical utility in lung cancer detection and diagnoses. PMID- 26279650 TI - Two New Cases of 1p21.3 Deletions and an Unbalanced Translocation t(8;12) among Individuals with Syndromic Obesity. AB - Obesity is a highly heritable but genetically heterogeneous disorder. Various well-known microdeletion syndromes (e.g. 1p36, 2q37, 6q16, 9q34, 17p11.2) can cause this phenotype along with intellectual disability (ID) and other findings. Chromosomal microarrays have identified 'new' microdeletion/duplication syndromes often associated with obesity. We report on 2 unrelated patients with an overlapping region of deletion at 1p21.3p21.2, and a third patient with a de novo recurrent unbalanced translocation der(8)t(8;12)(p23.1;p13.31), detected by 180K array CGH in a prospective cohort of syndromic obesity patients. Deletion of 1p21.3 is a rare condition, and there have been only 11 cases of the same recurrent translocation between chromosomes 8 and 12 [t(8;12)] reported to date. The former has been associated with ID, autistic spectrum disorder (ASD) and mild dysmorphic features, and in 4 patients who were obese or had a tendency to obesity, a minimal overlapping region of 2 genes, DPYD and MIR137, was detected; t(8;12) has recently been recognized to cause a childhood obesity syndrome due to duplication of the GNB3 gene. Thus, our findings add to the existing literature on the clinical description of these new syndromes, providing additional support that these loci are associated with syndromic obesity. We suggest that heterozygous loss of MIR137 may contribute to obesity as well as ID and ASD. PMID- 26279651 TI - Phenotypic Variability Associated with a Large Recurrent 1q21.1 Microduplication in a Three-Generation Family. AB - Recurrent copy number variants of the q21.1 region of chromosome 1 have been associated with variable clinical features, including developmental delay, mild to moderate intellectual disability, psychiatric and behavioral problems, congenital heart malformations, and craniofacial abnormalities. A subset of individuals is clinically unaffected. We describe a unique 3-generation family with a large recurrent 1q21.1 microduplication (BP2-BP4). Our observations underline the incomplete penetrance and phenotypic variability of this rearrangement. We also confirm the association with congenital heart malformations, chronic depression, and anxiety. Furthermore, we report a broader range of dysmorphic features. The extreme phenotypic heterogeneity observed in this family suggests that additional factors modify the clinical phenotype. PMID- 26279652 TI - Novel Mutation and Structural RNA Analysis of the Noncoding RNase MRP Gene in Cartilage-Hair Hypoplasia. AB - Cartilage-hair hypoplasia (CHH) is an autosomal recessive disorder which is characterized by bone metaphysis anomalies with manifestations that include short stature, defective cellular immunity, and predisposition to several cancers. It is caused by mutations in RMRP, which is transcribed as an RNA component of the mitochondrial RNA-processing ribonuclease. We report the clinical and molecular data of a Moroccan patient with CHH. Sequencing of RMRP identified 2 mutations in the patient: the known mutation g.97G>A and the variation g.27G>C, which has not been reported previously. Given the high mutational heterogeneity, the high frequency of variations in the region, and the fact that RMRP is a non-coding gene, assigning the pathogenicity to RMRP mutations remains a difficult task. Therefore, we compared the characteristics of the primary and secondary structures of mutated RMRP sequences. The location of our mutations within the secondary structure of the RMRP molecule revealed that the novel g.27G>C mutation causes a disruption in the Watson-Crick base pairing, which results in an impairment of a highly conserved P3 domain. Our work prompts considering the consequences of novel RMRP nucleotide variations on conserved RNA structures to gain insights into the pathogenicity of mutations. PMID- 26279653 TI - Cleidocranial Dysplasia with Normal Clavicles: A Report of a Novel Genotype and a Review of Seven Previous Cases. AB - We report an unusual combination of features comprising delayed tooth eruption and closure of the anterior fontanel as the sole presenting features in a child with cleidocranial dysplasia (CCD). Radiological survey revealed the presence of wormian bones in the skull, pseudoepiphysis at the base of the bilateral second metacarpal, and midline ossification defects at pubic symphysis in the presence of essentially normal clavicles. DNA sequencing of the RUNX2 gene detected a novel nonsense mutation in exon1 (c.166C>T; p.Q56X) in its glutamine-alanine (Q/A) repeat domain. The genotypes of all published cases of CCD with normal clavicles were reviewed. Additional dental and otolaryngological features were enlisted. Three cases with a milder dental phenotype and normal clavicles were associated with a mutation in the Q/A domain. Collectively, we found a novel CCD causing nonsense mutation p.Q56X in the Q/A domain of the RUNX2 gene. PMID- 26279654 TI - Intragenic Deletion in the LIFR Gene in a Long-Term Survivor with Stuve-Wiedemann Syndrome. AB - Stuve-Wiedemann syndrome (SWS, OMIM 601559) is a rare autosomal recessive bent bone dysplasia, caused by loss-of-function mutations in the leukemia inhibitory factor receptor (LIFR) gene, which usually leads to early death. Only few patients with long-term survival have been described in the literature. We report on a 5-year-old boy from a consanguineous marriage with molecular analysis for the LIFR gene. Sanger and next-generation sequencing (NGS) of LIFR were performed. Copy number variation analysis with NGS showed a novel mutation as the cause for the syndrome: an intragenic homozygous deletion in LIFR, involving exons 15-20. Bridging PCR was carried out to confirm the intragenic deletion. This is the first description of a large deletion in LIFR, broadening the spectrum of mutations in SWS. Besides the reported allelic heterogeneity, further studies such as exome sequencing are required to identify a novel gene in order to confirm the locus heterogeneity in SWS. PMID- 26279655 TI - Recurrent Nonconvulsive Status Epilepticus in a Patient with Coffin-Lowry Syndrome. AB - Coffin-Lowry syndrome (CLS) is a rare neurodevelopmental condition caused by heterogeneous mutations in the RPS6KA3 gene on the X chromosome, leading to severe intellectual disability and dysmorphism in men, while women are carriers and only weakly affected. CLS is well known for stimulus-induced drop episodes; however, epilepsy is not commonly reported in this condition. We report on a CLS patient presenting with recurrent episodes of nonconvulsive status epilepticus (NCSE) with generalized epileptic activity, for which investigations did not find any other cause than the patient's genetic condition. This case underlines that the possibility of nonconvulsive epileptic seizures and status epilepticus should, therefore, be considered in those patients. The treatable diagnosis of NCSE may easily be overlooked, as symptoms can be unspecific. PMID- 26279656 TI - Exome Sequencing Identification of EP300 Mutation in a Proband with Coloboma and Imperforate Anus: Possible Expansion of the Phenotypic Spectrum of Rubinstein Taybi Syndrome. AB - Rubinstein-Taybi syndrome (RSTS) is a multisystem developmental disorder characterized by facial dysmorphisms, broad thumbs and halluces, growth retardation, and intellectual disability. In about 8% of RSTS cases, mutations are found in EP300. Previously, the EP300 mutation has been shown to cause the highly variable RSTS phenotype. Using exome sequencing, we identified a de novo EP300 frameshift mutation in a proband with coloboma, facial asymmetry and imperforate anus with minimal RSTS features. Previous molecular studies have demonstrated the importance of EP300 in oculogenesis, supporting the possibility that EP300 mutation may cause ocular coloboma. Since a wide phenotypic spectrum is well known in EP300-associated RSTS cases, the atypical phenotype identified in our proband may be an example of rare manifestations of RSTS. PMID- 26279657 TI - Endovascular Treatment for Acute Ischemic Stroke: Considerations from Recent Randomized Trials. AB - BACKGROUND: Despite increasing use of intravenous recombinant tissue plasminogen activator therapy, the large number of patients ineligible for treatment or for whom treatment is ineffective has become problematic. SUMMARY: The number of endovascular treatments for acute ischemic stroke is increasing each year. This treatment provides higher recanalization rates for occluded vessels but may lead to hemorrhagic complications such as subarachnoid hemorrhage. Results were announced for three randomized controlled trials in 2013, with all failing to show the superiority of endovascular treatment. These results have had a major negative impact, but a new randomized controlled trial, the Multicenter Randomized CLinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN), showed that acute endovascular treatment was superior to standard medical treatment in terms of clinical outcomes. With this positive result, interim analyses from other randomized trials appear likely to show the effectiveness of endovascular treatment. KEY MESSAGE: Clinical evidence of acute stroke intervention using mechanical devices might be established in the near future. PMID- 26279658 TI - Spontaneous Thrombosis of a Ruptured Brain Arteriovenous Malformation: The Argument for Early Conservative Management. AB - Generally, definitive treatment of brain arteriovenous malformations (BAVM) presenting with hemorrhage is recommended to prevent recurrent hemorrhage. The risk of craniotomy and resection of BAVM has been well described using the Spetzler-Martin grading scale; however, the optimal timing for the definitive treatment of ruptured BAVM remains unclear. We report an interesting case of spontaneous BAVM thrombosis in which the patient presented with right occipital intracerebral hemorrhage caused by ruptured right occipital micro-BAVM. A preoperative angiogram 4 months later demonstrated spontaneous thrombosis of the AVM. Despite the risk of re-bleeding, the decision to defer treatment in the acute stage of illness in this case was based on the absence of high-risk angioarchitectural features in the arteriovenous malformations (AVM). It is important to emphasize the potential benefits of early conservative management, particularly in patients with low-risk angiographic features. We also review the literature of spontaneous BAVM thrombosis and discuss the potential benefit of early conservative management. PMID- 26279659 TI - Comparison of Intraoperative Indocyanine Green Angiography and Digital Subtraction Angiography for Clipping of Intracranial Aneurysms. AB - BACKGROUND: Residual aneurysm after microsurgical clipping carries a risk of aneurysm growth and rupture. Digital subtraction angiography (DSA) remains the standard to determine the adequacy of clipping. Intraoperative indocyanine green (ICG) angiography is increasingly utilized to confirm optimal clip positioning across the neck and to evaluate the adjacent vasculature. OBJECTIVE: We evaluated the correlation between ICG and DSA in clipped intracranial aneurysms. METHODS: A retrospective study of patients who underwent craniotomy and microsurgical clipping of intracranial aneurysms with ICG for 2 years. Patient characteristics, presentation details, operative reports, and pre- and postclipping angiographic images were reviewed to determine the adequacy of the clipping. RESULTS: Forty seven patients underwent clipping with ICG and postoperative DSA: 57 aneurysms were clipped; 23 patients (48.9%) presented with subarachnoid hemorrhage. Nine aneurysms demonstrated a residual on DSA not identified on ICG (residual sizes ranged from 0.5 to 4.3 mm; average size: 1.8 mm). Postoperative DSA demonstrated no branch occlusions. CONCLUSION: Intraoperative ICG is useful in the clipping of intracranial aneurysms to ensure a gross patency of branch vessels; however, the presence of residual aneurysms and subtle changes in flow in branch vessels is best seen by DSA. This has important clinical implications with regard to follow up imaging and surgical/endovascular management. PMID- 26279660 TI - Coil Embolization of Wide-Neck Bifurcation Aneurysms Using a Single-Balloon Microcatheter. AB - BACKGROUND: Coil embolization of wide-neck cerebral aneurysms frequently requires stent or balloon assistance. Such approaches to coil embolization increase the procedural complexity, adding risk and cost. OBJECTIVE: To describe a series of coil embolization procedures performed using a single-balloon microcatheter to treat wide-neck aneurysms and establish the safety, feasibility and efficacy of this technique. METHODS: A retrospective review was performed to identify cases in which the Ascent balloon (Codman Neurovascular, Raynham, Mass., USA) was used as a single-balloon microcatheter for aneurysm coil embolization at two institutions. Clinical, demographic and angiographic data were obtained, and aneurysm volumes as well as packing densities (PD) were calculated. RESULTS: Eight cerebral aneurysms were treated using this technique. Six of these were unruptured. The aneurysms had an average neck diameter of 3.7 mm, and the maximum dimension ranged from 5 to 11 mm, with a mean of 7.5 mm. The mean aspect ratio was 2.07. The mean volume of the aneurysms was 180.38 mm(3). The average PD achieved in these 8 aneurysms was 41.79%. Complete occlusion with coil embolization [Raymond-Roy Occlusion Classification (RROC) 1] was achieved in all cases except one, where a small residual was left deliberately and the occlusion grade was RROC 2. There were no intraprocedural complications. CONCLUSION: This initial experience demonstrates the feasibility and immediate outcomes of a single-balloon microcatheter technique in coil embolization of wide-neck cerebral aneurysms. This technique may be used to achieve a high PD, comparable to that obtained with stent-assisted coiling or coiling alone, while avoiding permanent stent placement and potentially reducing thromboembolic complications. PMID- 26279661 TI - Ipsilateral Infarct in Newly Diagnosed Cervical Internal Carotid Artery Atherosclerotic Occlusion. AB - OBJECTIVE: We aimed to determine factors associated with recent infarct (RI) in patients with newly identified atherosclerotic cervical internal carotid artery occlusion (CICAO). METHODS: This was a retrospective review of consecutive patients who underwent cervical CT angiography from 2002 to 2006 at a single tertiary center. RI was defined by positive diffusion-weighted imaging/apparent diffusion coefficient magnetic resonance imaging (MRI) in the correspondent CICAO territory. Subjects were dichotomized into those with a RI versus patients with no RI (No-RI). RESULTS: Of 2,459 patients with cervical CT angiograms in the study period, 108 (4.4%) had complete medical records and brain MRI and were included. The mean age was 64 +/- 13 years, 58% were men, and 62 (57%) had a RI. The demographics of the RI and No-RI patients were comparable, with the exception that those with RI had a lower frequency of coronary artery disease (CAD, 13 vs. 54%; p < 0.01) and dyslipidemia (38 vs. 69%; p < 0.01). The use of antiplatelets was not statistically different between the groups (56 vs. 71%; p = 0.1). Subjects with RI were less likely on statins (21 vs. 56%; p < 0.01) and antihypertensives (9 vs. 71%; p < 0.01). Multivariate regression revealed that CAD, the use of statins, and the use of antihypertensives were associated with No RI CICAO presentation. CONCLUSION: The use of statins and antihypertensives is associated with a decreased risk of RI atherosclerotic CICAO. PMID- 26279662 TI - Safety and Efficacy of Mechanical Thrombectomy Using Stent Retrievers in the Endovascular Treatment of Acute Ischaemic Stroke: A Systematic Review. AB - BACKGROUND: The treatment of choice for acute ischaemic stroke is the intravenous administration of recombinant tissue plasminogen activator within 3-4.5 h of symptom onset. However, the use of a thrombolytic would be limited by its narrow therapeutic window and contraindications. As a result, in recent years, techniques such as mechanical thrombectomy have emerged, which employ thrombus retrieval devices, such as stent retrievers (SolitaireTM, Trevo(r) or ReviveTM), whose safety and efficacy in the endovascular treatment of acute ischaemic stroke is analysed in this article. METHODS: A systematic literature search was undertaken until March 2015. The quality of evidence was assessed according to the GRADE methodology. A meta-analysis of the results of randomised controlled trials (RCTs) was performed, and the weighted average for the case series' sample size was calculated (Review Manager v5.2 and SPSS v19). RESULTS: Seventeen primary studies (2 RCTs, SolitaireTM and Trevo(r) vs. Merci(r), and 15 case series) were selected. The RCT results show that stent retrievers have a safety profile similar to the Merci(r) device. However, both SolitaireTM and Trevo(r) achieved a higher recanalisation success rate (OR, 4.56; 95% CI, 2.63-7.90; p < 0.00001) and appropriate clinical outcome at 90 days (OR, 2.54; 95% CI, 1.52 4.25; p < 0.0004), although the 90-day mortality rate was similar in both groups (OR, 0.75; 95% CI, 0.17-3.37; p = 0.70). CONCLUSIONS: Stent retrievers appear to be safe and effective devices, achieving high recanalisation rates and good clinical outcomes in the endovascular treatment of patients with acute ischaemic stroke due to the occlusion of intracranial arteries in comparison with the clot retriever Merci(r). PMID- 26279663 TI - Demographic and Technical Risk Factors of 30-Day Stroke, Myocardial Infarction, and/or Death in Standard- and High-Risk Patients Who Underwent Carotid Angioplasty and Stenting. AB - BACKGROUND: Carotid angioplasty and stenting (CAS) is an accepted treatment to prevent stroke in patients with carotid artery stenosis. The purpose of this study is to identify risk factors for major complications after CAS. MATERIALS AND METHODS: This is a prospective study that was conducted at Shiraz University of Medical Sciences in southern Iran from March 2011 to June 2014. Consecutive patients undergoing CAS were enrolled. Both standard- and high-risk patients for endarterectomy were enrolled. Demographic data, atherosclerotic risk factors, site of stenosis, degree of stenosis, and data regarding technical factors were recorded. Thirty-day stroke, myocardial infarction, and/or death were considered as the composite primary outcomes of the study. RESULTS: A total of 251 patients were recruited (mean age: 71.1 +/- 9.6 years; male: 65.3%). Of these, 178 (70.9%) were symptomatic, 73 (29.1%) were diabetic, 129 (51.4%) were hyperlipidemic, 165 (65.7%) were hypertensive, and 62 (24.7%) patients were smokers. CAS was performed for left internal carotid artery (ICA) in 113 (45.4%) patients. Fourteen (5.6%) patients had sequential bilateral stenting. Mean stenosis of operated ICA was 80.2 +/- 13.8%. An embolic protection device was used in 203 (96.2%) patients. Pre- and postdilation were performed in 39 (18.5%) and 182 (86.3%) patients, respectively. Composite outcomes were observed in 3.6% of patients (3.2% stroke, 0% myocardial infarction, and 1.2% death). Left-sided lesions and the presence of diabetes mellitus were significantly associated with poor short-term outcome (p = 0.025 and p = 0.020, respectively). CONCLUSION: There was a higher risk of short-term major complications in diabetic patients and for left carotid artery intervention. PMID- 26279664 TI - Early Experience with the TransFormTM Occlusion Balloon Catheter: A Single-Center Study. AB - BACKGROUND AND OBJECTIVE: Balloon-assisted coil embolization has become an important adjunct in the endovascular treatment of intracranial aneurysms. The management of broad-necked cerebral aneurysms is technically perplexed due to a variety of factors, which include the difficulty in defining the aneurysm-parent vessel interface angiographically and problems in achieving complete aneurysmal occlusion. This could later predispose to regrowth or recanalization. We sought to determine the safety and efficacy of the TransFormTM occlusion balloon catheter (TOBC) for the coiling of intracranial aneurysms at our institute. METHODS: A retrospective review was performed to identify TOBC cases between May 1, 2013, and April 30, 2014. RESULTS: A total of 24 TOBC cases were identified. In 23 cases, the TOBC was used for balloon-remodeled coil embolization, and in 1 case, it was used for vasospasm treatment alone. Out of the total 24 cases in which the TOBC was used, 16 (66.6%) were ruptured aneurysms. Stents were used in 6/23 (26%) cases. In all cases, the balloon could be placed as intended. The inflation and deflation times ranged from 3 to 4 s. No serious complications were noted. In the experience of the authors, the balloon performed the intended role in most cases. CONCLUSIONS: This series shows that the TOBC is feasible, safe and useful in the treatment of cerebral aneurysms. The balloon was traceable to the intended site and the preparation, inflation and deflation times were short. We believe that the TOBC has effective utility in treating broad-necked and small aneurysms. PMID- 26279665 TI - Neurointerventional Stenting and Antiplatelet Function Testing: To Do or Not to Do? AB - BACKGROUND AND PURPOSE: Platelet function testing in neurointerventional (NI) procedures is still controversial. We compared the clinical outcomes between antiplatelet responders and nonresponders based on the results of the VerifyNow (VN) testing method. METHODS: This is a retrospective single-center analysis of all consecutive patients who underwent NI stenting procedures from January 2007 through July 2013 and had documented preprocedural aspirin (ASA) and clopidogrel VN assays. Patients were divided into two groups based on their responsiveness to antiplatelet. Baseline characteristics, good functional outcome measured by the modified Rankin Scale (mRS) at 90 days, combined procedural complication rate defined as postprocedural stroke, in-stent thrombosis, and intraoperative rupture were compared between the two groups. RESULTS: Our cohort included 37 patients: 26 were in the responder group (RG) and 11 were in the nonresponder group (NRG). Baseline characteristics were similar between the two groups. Even though the combined complication rate was similar between the two groups [NRG: 2/11 (18%) vs. RG: 2/26 (7%); p = 0.33], there was a trend for a higher rate of good functional outcome (90-day mRS: 0-2) in the RG (22/22, 100%) as compared to the NRG (8/10, 80%) (p = 0.0907). CONCLUSION: Overall, utilizing the VN antiplatelet function testing did not significantly change the clinical outcome after the NI procedures. Larger randomized trials are warranted to provide a better understanding of the utility of the antiplatelet testing in NI stenting procedures. PMID- 26279666 TI - Bayesian Small Area Estimates of Diabetes Incidence by United States County, 2009. AB - In the United States, diabetes is common and costly. Programs to prevent new cases of diabetes are often carried out at the level of the county, a unit of local government. Thus, efficient targeting of such programs requires county level estimates of diabetes incidence-the fraction of the non-diabetic population who received their diagnosis of diabetes during the past 12 months. Previously, only estimates of prevalence-the overall fraction of population who have the disease-have been available at the county level. Counties with high prevalence might or might not be the same as counties with high incidence, due to spatial variation in mortality and relocation of persons with incident diabetes to another county. Existing methods cannot be used to estimate county-level diabetes incidence, because the fraction of the population who receive a diabetes diagnosis in any year is too small. Here, we extend previously developed methods of Bayesian small-area estimation of prevalence, using diffuse priors, to estimate diabetes incidence for all U.S. counties based on data from a survey designed to yield state-level estimates. We found high incidence in the southeastern United States, the Appalachian region, and in scattered counties throughout the western U.S. Our methods might be applicable in other circumstances in which all cases of a rare condition also must be cases of a more common condition (in this analysis, "newly diagnosed cases of diabetes" and "cases of diabetes"). If appropriate data are available, our methods can be used to estimate proportion of the population with the rare condition at greater geographic specificity than the data source was designed to provide. PMID- 26279667 TI - Duplicate analysis method: a cheaper alternative to commercial IQC materials in limited resource settings for monitoring CD4 testing. AB - BACKGROUND: India has a large number of HIV infected patients being followed up at anti-retroviral therapy (ART) centers. The patients are regularly offered CD4 count estimation for deciding their eligibility for ART initiation as well as for monitoring response to ART, making CD4 count estimation a very critical test. Hence, quality control of CD4 testing is utmost important for ultimate success of ART program. As the commercial controls are very expensive, internal quality control (IQC), at present, is being done by duplicate analysis method using previous day samples in most of the laboratories. Hence the study was undertaken to review performance of duplicate analysis method for monitoring daily IQC. METHODS: Quality control (QC) data from 11 Indian laboratories using duplicate analysis and/or commercial controls for IQC of CD4 testing was collected for reviewing information on QC parameters such as precision, accuracy and trend monitoring. Precision was determined by r(2) values and mean % variation for duplicate analysis and coefficient of variation (% CV) for commercial controls. Accuracy was monitored by rate of QC failures for both the types of control and trend monitoring was done by plotting LJ charts for commercial controls and by plotting daily % variation for duplicate analysis. RESULTS: The laboratories using duplicate analysis for IQC showed good precision with mean % variation ranging from 0.5 to 7.2. There was good match between r(2) values and % CV of the laboratories performing both the types of QC methods. Rates of QC failures were 2.3 for duplicate analysis and 3 per laboratory-year for IMMUNO-TROL controls. Daily trend monitoring showed fluctuation of daily counts around mean in LJ charts and of percent variation around 0% in duplicate analysis method. Commercially available controls showed limitations such as altered specimen quality leading to difficulties in manual gating and issues with the establishment of laboratory range. CONCLUSION: Duplicate analysis can serve as a cheaper alternative to commercially available controls for IQC of CD4 testing especially when supplemented with other QC measures for controlling variations caused by reagent, equipment, staff and environment in addition to the successful participation in External Quality Assurance programme. PMID- 26279668 TI - Impact of highly active antiretroviral therapy on hematological indices among HIV 1 infected children at Kenyatta National Hospital-Kenya: retrospective study. AB - BACKGROUND: HIV infected children experience a range of hematological complications which show marked improvement within 6 months of initiating anti retroviral therapy. The Objectives of the study was to describe the changes in hematological indices of HIV-1 infected children following 6 months of treatment with first line antiretroviral drugs (ARVs) regimen. METHODS: A retrospective study was conducted between September and November 2008. During this period medical records of children attending Comprehensive Care Clinic at Kenyatta National hospital were reviewed daily. HIV infected children aged 5-144 months were enrolled if they had received antiretroviral drugs for at least 6 months with available and complete laboratory results. RESULTS: Medical records of 337 children meeting enrollment criteria were included in the study. The median age was 63 months with equal male to female ratio. Following 6 months of HAART, prevalence of anemia (Hemoglobin (Hb) <10 g/dl) declined significantly from 35.9 to 16.6 % a nearly 50 % reduction in the risk of anemia RR = 0.56 [(95 % CI 0.44, 0.70) p < 0.001]. There was significant increase in Hb, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and platelets above the baseline measurements (p < 0.0001) and a significant decline in total white blood cell counts >11,000 cell/mm(3) but a none significant decrease in red blood cells (RBC). Pre-HAART, World Health Organization (WHO) stage 3 and 4 was associated with a ten-fold increased likelihood of anemia. Chronic malnutrition was associated with anemia but not wasting and immunologic staging of disease. CONCLUSION: Hematological abnormalities changed significantly within 6 months of antiretroviral therapy with significant increase in hemoglobin level, MCV, MCH and platelet and decrease in WBC and RBC. PMID- 26279669 TI - HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. AB - BACKGROUND: Although injection drug use drives antiretroviral drug resistance, the prevalence of protease inhibitor (PI) resistance among Kenyan IDUs remains undetermined. We, therefore, explored PI resistance mutations and their association with viral load and CD4+ T cell counts in HIV-1 infected IDUs (ART naive, n = 32; and -experienced, n = 47) and non-drug users (ART-naive, n = 21; and -experienced, n = 32) naive for PI treatment from coastal Kenya. RESULTS: Only IDUs harboured major PI resistance mutations consisting of L90M, M46I and D30 N among 3 (6.4 %) ART-experienced and 1 (3.1 %) -naive individuals. Minor PI mutations including A71T, G48E, G48R, I13V, K20I, K20R, L10I, L10V, L33F, L63P, T74S, V11I, and V32L were detected among the ART-experienced (36.2 vs. 46.9 %) and -naive (43.8 vs. 66.7 %) IDUs and non-drug users, respectively. All the four IDUs possessing major mutations had high viral load while three presented with CD4+ T cell counts of <500 cells/ml. Among the ART-naive non-drug users, CD4+ T cell counts were significantly lower in carriers of minor mutations compared to non-carriers (P < 0.05). CONCLUSION: Transmitted drug resistance may occur in IDUs underscoring the need for genotyping resistance before initiating PI treatment. PMID- 26279670 TI - Scoliosis-Specific exercises can reduce the progression of severe curves in adult idiopathic scoliosis: a long-term cohort study. AB - BACKGROUND: Scoliosis fusion surgery is generally considered the only means to stop the progression of adult idiopathic scoliosis (ADIS), but for patients refusing surgery there is lack of evidence in favour of conservative treatment. The aim of the present study was to verify the possible effectiveness of scoliosis-specific exercises when facing ADIS progression. METHODS: We designed a retrospective cohort study. We included 34 ADIS patients in treatment at our Institute (5 males and 29 females, mean age was 38.0 +/- 11.0), exclusively treated with specific Scoliosis Specific SEAS exercises. INSTRUMENTATION: SEAS exercises are scoliosis-specific exercises. In adult patients they are aimed to recover postural collapse, postural control and vertebral stability through an active self-correction. Postural integration is a key element, including the neuromotor integration of correct postures and an ergonomic education program. Therapy includes at least two weekly exercise sessions each lasting 45 min. OUTCOME MEASURES: Radiographic progression was the main outcome and it was analysed as a continuous variable. STATISTICS: One way ANOVA and paired t-test were applied for continuous data, while chi-square test was applied for categorical data. Alpha was set at 0.05. RESULTS: The mean Cobb angle of the patients included into the present study, was 55.8 +/- 13.2 degrees . Fifteen patients had previous x-rays testifying scoliosis progression: the average curve progression (worsening) was 9.8 +/- 6.6 degrees at a median of 25 (range 17-48) years. The remaining were characterized by more severe curves, exceeding 40 degrees Cobb (mean curvature 50.9 +/- 13.6) but it was not possible to prove that the curves had progressed in these cases. After an average period of 2 years of treatment (range 1-18y), 68 % of the patients experienced an improvement in their scoliosis. However in one patient (3 %) the scoliosis worsened by 5 degrees in 18 years (progression rate reduced from 0.5 degrees to 0.27 degrees per year). Patients improved 4.6 +/- 5.0 degrees Cobb (P < 0.05), with no differences based on the localization of the curve, gender, age, length of treatment, Cobb degrees at the start of observation or treatment. CONCLUSIONS: Scoliosis Specific SEAS Exercises proved to be superior to natural history in ADIS, at least in individual cases and should be considered as a first line treatment especially in patients refusing scoliosis surgery. PMID- 26279671 TI - Research quality in scoliosis conservative treatment: state of the art. AB - The publication of research in the field of conservative treatment of scoliosis is increasing after a long period of progressive decline. In 2014, three high quality and scientifically sound papers gave new strength to the conservative scoliosis approach. The efficacy of treatment over observation was demonstrated by two RCTs for bracing, and one for scoliosis-specific exercises provided by a physical therapist. It is difficult to design strong studies in this field due to the long time needed for follow up and the challenge of recruiting patients and families willing to be involved in the decision process. Nevertheless, the main methodological errors are not related to the study design but rather on the way it is performed, which very frequently affects the reliability of results. The most common errors are: selection bias, with many studies including functional rather than a true structural scoliosis; inappropriate outcome measures, utilizing parameters not related to scoliosis progression or quality of life; inappropriate follow up, reporting only immediate results and not addressing end of growth results; an incorrect interpretation of findings, with an overestimation of results; and missing the evaluation of skeletal maturity, without which results cannot be considered stable. Being aware of these errors is extremely important both for authors and for readers in order to avoid questionable practices based on inconclusive studies that could harm patients. PMID- 26279672 TI - Trauma resuscitation requiring massive transfusion: a descriptive analysis of the role of ratio and time. AB - OBJECTIVE: We aimed to evaluate whether early administration of high plasma to red blood cells ratios influences outcomes in injured patients who received massive transfusion protocol (MTP). METHODS: A retrospective analysis was conducted at the only level 1 national trauma center in Qatar for all adult patients(>=18 years old) who received MTP (>=10 units) of packed red blood cell (PRBC) during the initial 24 h post traumatic injury. Data were analyzed with respect to FFB:PRBC ratio [(high >= 1:1.5) (HMTP) vs. (low < 1:1.5) (LMTP)] given at the first 4 h post-injury and also between (>4 and 24 h). Mortality, multiorgan failure (MOF) and infectious complications were studied as well. RESULTS: During the study period, a total of 4864 trauma patients were admitted to the hospital, 1.6 % (n = 77) of them met the inclusion criteria. Both groups were comparable with respect to initial pH, international normalized ratio, injury severity score, revised trauma score and development of infectious complications. However, HMTP was associated with lower crude mortality (41.9 vs. 78.3 %, p = 0.001) and lower rate of MOF (48.4 vs. 87.0 %, p = 0.001). The number of deaths was 3 times higher in LMTP in comparison to HMTP within the first 30 days (36 vs. 13 cases). The majority of deaths occurred within the first 24 h (80.5 % in LMTP and 69 % in HMTP) and particularly within the first 6 h (55 vs. 46 %). CONCLUSIONS: Aggressive attainment of high FFP/PRBC ratios as early as 4 h post-injury can substantially improve outcomes in trauma patients. PMID- 26279674 TI - Chemistry Central Journal themed issue: Dial-a-Molecule. PMID- 26279673 TI - IROA: the International Register of Open Abdomen.: An international effort to better understand the open abdomen: call for participants. AB - Actually the most common indications for Open Abdomen (OA) are trauma, abdominal sepsis, severe acute pancreatitis and more in general all those situations in which an intra-abdominal hypertension condition is present, in order to prevent the development of an abdominal compartment syndrome. The mortality and morbidity rate in patients undergone to OA procedures is still high. At present many studies have been published about the OA management and the progresses in survival rate of critically ill trauma and septic surgical patients. However several issues are still unclear and need more extensive studies. The definitions of indications, applications and methods to close the OA are still matter of debate. To overcome this lack of high level of evidence data about the OA indications, management, definitive closure and follow-up, the World Society of Emergency Surgery (WSES) promoted the International Register of Open Abdomen (IROA). The register will be held on a web platform (Clinical Registers(r)) through a dedicated web site: www.clinicalregisters.org. This will allow to all surgeons and physicians to participate from all around the world only by having a computer and a web connection. The IROA protocol has been approved by the coordinating center Ethical Committee (Papa Giovanni XXIII hospital, Bergamo, Italy). IROA has also been registered to ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT02382770). PMID- 26279675 TI - Validation of the CogState battery for rapid neurocognitive assessment in Ugandan school age children. AB - BACKGROUND: CogState is a widely used computer-based cognitive test whose validity has not been addressed in resource poor settings. We examined the construct, concurrent and convergent validity of CogState, test-retest reliability and the effect of sociodemographic variables on CogState outcomes in school age children. METHODS: Two hundred and thirty Ugandan children (54% male) with mean age 6.99 years (SD = 1.67, range 5-13 years) were assessed using CogState, the Kaufman Assessment Battery for Children, 2nd edition (KABC-II) and the Test of Variables of Attention (TOVA) at baseline and 8 weeks later. Correlations were run between CogState and the KABC-II and TOVA to evaluate its concurrent and convergent validity. Factor analysis was used to evaluate construct validity of CogState. Correlations between baseline and 8 weeks CogState scores were used to determine the test-retest reliability while general linear models were used to assess associations with sociodemographic factors. RESULTS: Significant correlations were observed between CogState's One Card Learning, One Back Memory and Card Detection with the TOVA and between CogState's Maze Chase and One Back Memory with KABC-II's Simultaneous Processing. CogState had a three factor structure with Processing Speed, Processing Accuracy and Maze Chase and Maze Learning. CogState had low to moderate test-retest reliability in Ugandan children with correlations ranging from 0.32 to 0.57. Age, sex and education were associated with CogState outcomes. CONCLUSIONS: CogState is a valid and reliable test battery for rapid computer-based neurocognitive assessment in Ugandan children and can thus be used in this cultural context. PMID- 26279677 TI - Evaluating the effects of biocompatible cholinium ionic liquids on microbial lipid production by Trichosporon fermentans. AB - BACKGROUND: Microbial lipid is a potential raw material for large-scale biodiesel production and lignocellulosic hydrolysate has been considered as promising low cost substrate for lipid fermentation. Lignocellulosic biomass needs to be pretreated before enzymatic hydrolysis, and biocompatible cholinium ionic liquids (ILs) have been demonstrated to be highly efficient for pretreatment. However, the impact of these ILs residues in hydrolysates on downstream biotransformation remains unknown. Therefore, the influence of three typical cholinium ILs on the lipid production by Trichosporon fermentans was first investigated. RESULTS: The cell growth of T. fermentans was stimulated in the presence of cholinium lysine ([Ch][Lys]) and cholinium serine ([Ch][Ser]), while the lipid accumulation was inhibited by [Ch][Lys]) and [Ch][Ser]. Both cell growth and lipid accumulation of T. fermentans were inhibited in the presence of cholinium acetate ([Ch][OAc]). Despite the reduction in lipid content, the lipid production by T. fermentans was improved in the presence of low concentrations of [Ch][Lys] (<=30 mM) and [Ch][Ser] (<=20 mM) due to the remarkable increase of biomass. It was found that cholinium cation had minor influence on lipid production. However, the anions of [Ch][Lys] and [Ch][Ser] could be assimilated as nitrogen source by T. fermentans and the reduced C/N ratio accounts for the inhibition of lipid accumulation, which could be alleviated by improving C/N ratio of medium. In addition, the anion of [Ch][OAc] could be metabolized by T. fermentans, leading to a rapid alkaline-pH shift and strong inhibition of lipid production. And this inhibitory effect on lipid production could be significantly reduced by controlling culture pH. CONCLUSIONS: The anions of [Ch][Lys], [Ch][Ser] and [Ch][OAc] play an important role in affecting the cell growth and lipid accumulation of T. fermentans, and the inhibition of these three ILs on lipid production can be alleviated by careful fermentation condition control. Hence, T. fermentans is a promising strain for microbial lipid production from cholinium ILs-pretreated lignocellulosic hydrolysates. PMID- 26279676 TI - Insertion of a xylanase in xylose binding protein results in a xylose-stimulated xylanase. AB - BACKGROUND: Product inhibition can reduce catalytic performance of enzymes used for biofuel production. Different mechanisms can cause this inhibition and, in most cases, the use of classical enzymology approach is not sufficient to overcome this problem. Here we have used a semi-rational protein fusion strategy to create a product-stimulated enzyme. RESULTS: A semi-rational protein fusion strategy was used to create a protein fusion library where the Bacillus subtilis GH11 xylanase A (XynA) was inserted at 144 surface positions of the Escherichia coli xylose binding protein (XBP). Two XynA insertions at XBP positions 209 ([209]XBP-Xyn-XBP) and 262 ([262]XBP-Xyn-XBP) showed a 20% increased xylanolytic activity in the presence of xylose, conditions where native XynA is inhibited. Random linkers of 1-4 Gly/Ala residues were inserted at the XynA N- and C-termini in the [209]XBP and [262]XBP, and the chimeras 2091A and 2621B were isolated, showing a twofold increased xylanolytic activity in the presence of xylose and k cat values of 200 and 240 s(-1) in the 2091A and 2621B, respectively, as compared to 70 s(-1) in the native XynA. The xylose affinity of the XBP was unchanged in the chimeras, showing that the ~3- to 3.5-fold stimulation of catalytic efficiency by xylose was the result of allosteric coupling between the XBP and XynA domains. Molecular dynamics simulations of the chimeras suggested conformation alterations in the XynA on xylose binding to the XBP resulted in exposure of the catalytic cavity and increased mobility of catalytic site residues as compared to the native XynA. CONCLUSIONS: These results are the first report of engineered glycosyl hydrolase showing allosteric product stimulation and suggest that the strategy may be more widely employed to overcome enzyme product inhibition and to improve catalytic performance. Graphical abstractProtein fusion of a GH11 xylanase (in red) and a xylose binding protein (XBP, in blue) results in a xylanase-XBP chimera that presents allosteric activation of the xylanase activity by xylose (shown as a space-filled molecule bound to the xylanase-XBP chimera). PMID- 26279678 TI - Cellobionic acid utilization: from Neurospora crassa to Saccharomyces cerevisiae. AB - BACKGROUND: Economical production of fuels and chemicals from plant biomass requires the efficient use of sugars derived from the plant cell wall. Neurospora crassa, a model lignocellulosic degrading fungus, is capable of breaking down the complex structure of the plant cell wall. In addition to cellulases and hemicellulases, N. crassa secretes lytic polysaccharide monooxygenases (LPMOs), which cleave cellulose by generating oxidized sugars-particularly aldonic acids. However, the strategies N. crassa employs to utilize these sugars are unknown. RESULTS: We identified an aldonic acid utilization pathway in N. crassa, comprised of an extracellular hydrolase (NCU08755), cellobionic acid transporter (CBT-1, NCU05853) and cellobionic acid phosphorylase (CAP, NCU09425). Extracellular cellobionic acid could be imported directly by CBT-1 or cleaved to gluconic acid and glucose by a beta-glucosidase (NCU08755) outside the cells. Intracellular cellobionic acid was further cleaved to glucose 1-phosphate and gluconic acid by CAP. However, it remains unclear how N. crassa utilizes extracellular gluconic acid. The aldonic acid pathway was successfully implemented in Saccharomyces cerevisiae when N. crassa gluconokinase was co expressed, resulting in cellobionic acid consumption in both aerobic and anaerobic conditions. CONCLUSIONS: We successfully identified a branched aldonic acid utilization pathway in N. crassa and transferred its essential components into S. cerevisiae, a robust industrial microorganism. PMID- 26279679 TI - De novo microduplication of CHL1 in a patient with non-syndromic developmental phenotypes. AB - BACKGROUND: The CHL1 gene codes for a member of the L1 family of neural cell adhesion molecules. It is highly expressed in the central and peripheral nervous system playing an important role in the building and functioning on the brain. CHL1 proteins are also involved in axonal migration, synaptic formation and plasticity. In mice, functional studies showed that the haploinsufficiency of Chl1 gene in the developing brain results in cognitive deficits suggesting that the CHL1 gene at 3p26.3 is a candidate for an autosomal form of intellectual disability. Furthermore, in humans deletions of CHL1 have been described in patients with neurodevelopmental delay characterized by learning and language difficulties, seizures. Less is known about the potential effect of CHL1 overexpression, and microduplications of CHL1 have been rarely identified. CASE PRESENTATION: In this report, we describe a male patient with a phenotype characterized by developmental delay, symptoms of hyperactivity, short attention span and speech delay. In addition, minor facial dysmorphic features have been observed. Chromosomal microarray analysis revealed a rare de novo 0.85 Mb microduplication on the short arm (p26.3) of chromosome 3, encompassing a single gene, CHL1. To the best of our knowledge, duplication of chromosome 3p26.3, including only the CHL1 gene, has been described in only one intellectually disabled girl with epilepsy. The duplication described here is the smallest reported so far. In addition, this is the first report describing a patient in which the CHL1 duplication is a de novo event. CONCLUSIONS: The clinical and molecular findings reported here are useful to provide further evidence that CHL1 is a dosage sensitive gene suggesting that not only the deletion but also its duplication can cause non-syndromic neurodevelopmental phenotypes. PMID- 26279680 TI - Parent-to-Child Transition in Managing Cystic Fibrosis: A Research Synthesis. AB - Although parents and children must adhere to five primary treatments for cystic fibrosis (CF), and their roles transition over time, the scope of CF studies often has been limited to one treatment regimen or to children within a specified age range. The purpose of this mixed research synthesis study is to integrate findings from qualitative and quantitative studies addressing the transition of CF management from parent to child, as well as factors related to adherence across treatments and over time. An existing grounded theory was used as a framework to synthesize findings in 17 reports from 16 studies. The results confirm the theory and posit three additional factors that may influence parent to-child transition of care management. PMID- 26279681 TI - Role of Ccr4-Not complex in heterochromatin formation at meiotic genes and subtelomeres in fission yeast. AB - BACKGROUND: Heterochromatin is essential for chromosome segregation, gene silencing and genome integrity. The fission yeast Schizosaccharomyces pombe contains heterochromatin at centromeres, subtelomeres, and mating type genes, as well as at small islands of meiotic genes dispersed across the genome. This heterochromatin is generated by partially redundant mechanisms, including the production of small interfering RNAs (siRNAs) that are incorporated into the RITS protein complex (RNAi-Induced Transcriptional Silencing). The assembly of heterochromatin islands requires the function of the RNA-binding protein Mmi1, which recruits RITS to its mRNA targets and to heterochromatin islands. In addition, Mmi1 directs its targets to an exosome-dependent RNA elimination pathway. RESULTS: Ccr4-Not is a conserved multiprotein complex that regulates gene expression at multiple levels, including RNA degradation and translation. We show here that Ccr4-Not is recruited by Mmi1 to its RNA targets. Surprisingly, Ccr4 and Caf1 (the mRNA deadenylase catalytic subunits of the Ccr4-Not complex) are not necessary for the degradation or translation of Mmi1 RNA targets, but are essential for heterochromatin integrity at Mmi1-dependent islands and, independently of Mmi1, at subtelomeric regions. Both roles require the deadenylase activity of Ccr4 and the Mot2/Not4 protein, a ubiquitin ligase that is also part of the complex. Genetic evidence shows that Ccr4-mediated silencing is essential for normal cell growth, indicating that this novel regulation is physiologically relevant. Moreover, Ccr4 interacts with components of the RITS complex in a Mmi1-independent manner. CONCLUSIONS: Taken together, our results demonstrate that the Ccr4-Not complex is required for heterochromatin integrity in both Mmi1-dependent and Mmi1-independent pathways. PMID- 26279684 TI - Genome architecture of Lactobacillus plantarum PS128, a probiotic strain with potential immunomodulatory activity. AB - BACKGROUND: Clinical and preclinical observations indicate that Lactobacillus plantarum has anti-inflammatory activity and may regulate the immune responses of its hosts when ingested. Recently, modification of teichoic acids (TAs) produced by L. plantarum was reported as a key to regulating the systemic immune response in mice. However, data linking TA-related genetic determinants and the immunomodulatory effect are limited. To provide genomic information for elucidating the underlying mechanism of immunomodulation by L. plantarum, we sequenced the genome of L. plantarum strain PS128. RESULTS: The PS128 genome contains 11 contigs (3,325,806 bp; 44.42% GC content) after hybrid assembly of sequences derived with Illumina MiSeq and PacBio RSII systems. The most abundant functions of the protein-coding genes are carbohydrate, amino acid, and protein metabolism. The 16S rDNA sequences of PS128 are closest to the sequences of L. plantarum WCFS1 and B21; these three strains form a distinct clade based on 16S rDNA sequences. PS128 shares core genes encoding the metabolism, transport, and modification of TAs with other sequenced L. plantarum strains. Compared with the TA-related genes of other completely sequenced L. plantarum strains, the PS128 contains more lipoteichoic acid exporter genes. CONCLUSIONS: We determined the draft genome sequence of PS128 and compared its TA-related genes with those of other L. plantarum strains. Shared genomic features with respect to TA-related subsystems may be important clues to the mechanism by which L. plantarum regulates its host immune responses, but unique TA-related genetic determinants should be further investigated to elucidate strain-specific immunomodulatory effects. PMID- 26279683 TI - Prevalence and microbiological characteristics of clinically infected foot-ulcers in patients with rheumatoid arthritis: a retrospective exploratory study. AB - BACKGROUND: The prevalence of foot ulcers in patients with rheumatoid arthritis (RA) has been reported at almost 10 %. These foot ulcers often occur at multiple sites and are reoccurring, with the potential risk of infection increased due to RA diagnosis and disease modifying medications. The objective of this study was to estimate the prevalence of clinical infection in foot-ulcers of patients with RA; describe the microbiological characteristics and investigate risk factors. METHODS: Retrospective clinical data was collected for all patients attending a rheumatology foot ulcer clinic between 1st May 2012 and 1st May 2013: wound swab data was collected from those with clinical infection. RESULTS: Twenty-eight patients with RA and foot-ulcers were identified; eight of these patients had clinical infection and wound swabs taken (29 %). Of these eight patients there were equal men and women, with median age 74 years, and average disease duration 22 years. Cardiovascular disease/peripheral-vascular disease (CVD/PVD) were reported in six patients, diabetes in two patients. Six patients were treated with disease-modifying anti-rheumatic drugs (DMARDs); three were on biologic medications and two on steroids. Five wound swabs cultured skin flora, one staphylococcus aureus, one had no growth after culture; and one was rejected due to labelling error. CONCLUSION: Almost a third of people with RA and foot ulcers attending clinic over one year had clinical infection, however microbiological analysis failed to isolate pathogens in six of seven wound swabs. This may be due to inaccurate diagnosis of ulcer infection or to issues with sampling, collection, transport, analysis or reporting. There was insufficient data to relate risk of clinical infection with risk factors. Further research is required to identify the most appropriate techniques for infection diagnosis, wound sampling and processing. TRIAL REGISTRATION: Ethical approval was obtained from University of Leeds, Faculty of Medicine and Health (Reference number: SHREC/RP/349). PMID- 26279682 TI - Non-surgical treatment of pain associated with posterior tibial tendon dysfunction: study protocol for a randomised clinical trial. AB - BACKGROUND: Symptoms associated with pes planovalgus or flatfeet occur frequently, even though some people with a flatfoot deformity remain asymptomatic. Pes planovalgus is proposed to be associated with foot/ankle pain and poor function. Concurrently, the multifactorial weakness of the tibialis posterior muscle and its tendon can lead to a flattening of the longitudinal arch of the foot. Those affected can experience functional impairment and pain. Less severe cases at an early stage are eligible for non-surgical treatment and foot orthoses are considered to be the first line approach. Furthermore, strengthening of arch and ankle stabilising muscles are thought to contribute to active compensation of the deformity leading to stress relief of soft tissue structures. There is only limited evidence concerning the numerous therapy approaches, and so far, no data are available showing functional benefits that accompany these interventions. METHODS: After clinical diagnosis and clarification of inclusion criteria (e.g., age 40-70, current complaint of foot and ankle pain more than three months, posterior tibial tendon dysfunction stage I & II, longitudinal arch flattening verified by radiography), sixty participants with posterior tibial tendon dysfunction associated complaints will be included in the study and will be randomly assigned to one of three different intervention groups: (i) foot orthoses only (FOO), (ii) foot orthoses and eccentric exercise (FOE), or (iii) sham foot orthoses only (FOS). Participants in the FOO and FOE groups will be allocated individualised foot orthoses, the latter combined with eccentric exercise for ankle stabilisation and strengthening of the tibialis posterior muscle. Participants in the FOS group will be allocated sham foot orthoses only. During the intervention period of 12 weeks, all participants will be encouraged to follow an educational program for dosed foot load management (e.g., to stop activity if they experience increasing pain). Functional impairment will be evaluated pre- and post-intervention by the Foot Function Index. Further outcome measures include the Pain Disability Index, Visual Analogue Scale for pain, SF 12, kinematic data from 3D-movement analysis and neuromuscular activity during level and downstairs walking. Measuring outcomes pre- and post-intervention will allow the calculation of intervention effects by 3*3 Analysis of Variance (ANOVA) with repeated measures. DISCUSSION: The purpose of this randomised trial is to evaluate the therapeutic benefit of three different non-surgical treatment regimens in participants with posterior tibial tendon dysfunction and accompanying pes planovalgus. Furthermore, the analysis of changes in gait mechanics and neuromuscular control will contribute to an enhanced understanding of functional changes and eventually optimise conservative management strategies for these patients. TRIAL REGISTRATION: ClinicalTrials.gov Protocol Registration System: ClinicalTrials.gov ID NCT01839669. PMID- 26279685 TI - The evolving role of the pathologist in the management of lung cancer. AB - Major advances in pathology, molecular biology, patient diagnosis and care, as well as the advent of personalized therapy, have resulted in a greatly increased role for the pathologist, who has emerged as a key member of the lung cancer management team. A new multidisciplinary, clinically relevant classification of pulmonary adenocarcinoma has resulted in a paradigm shift in how we view and practice lung cancer pathology. In the future, the role of the pathologist will continue to grow and become fully integrated with clinical care. PMID- 26279686 TI - Work-related road safety in Australia, the United Kingdom and the United States of America: an overview of regulatory approaches and recommendations to enhance strategy and practice. AB - Work-related travel and transport by road is fundamental for industry, government and organisations. Traditionally, road safety interventions at societal level have focussed on improving road and vehicle engineering and changing road-user behaviour through transport laws and safety campaigns. Crash data indicate that significant numbers of road-user fatalities occur while driving to or for work. Therefore, workplace initiatives can improve both road and worker safety. This paper reviews regulatory approaches to work-related road safety (WRRS) in Australia, the United Kingdom and United States, identifying significant and consistent gaps in policy, management and research. In all three countries, responsibility for managing and regulating WRRS is spread across government agencies, without a single coordinating body. This paper makes the case that integrating management of WRRS into regulatory and non-regulatory occupational health and safety (OHS) initiatives would foster and support collaboration between research and practice communities, ensuring a comprehensive evidence base for future programs. PMID- 26279687 TI - MassCascade: Visual Programming for LC-MS Data Processing in Metabolomics. AB - Liquid chromatography coupled to mass spectrometry (LC-MS) is commonly applied to investigate the small molecule complement of organisms. Several software tools are typically joined in custom pipelines to semi-automatically process and analyse the resulting data. General workflow environments like the Konstanz Information Miner (KNIME) offer the potential of an all-in-one solution to process LC-MS data by allowing easy integration of different tools and scripts. We describe MassCascade and its workflow plug-in for processing LC-MS data. The Java library integrates frequently used algorithms in a modular fashion, thus enabling it to serve as back-end for graphical front-ends. The functions available in MassCascade have been encapsulated in a plug-in for the workflow environment KNIME, allowing combined use with e.g. statistical workflow nodes from other providers and making the tool intuitive to use without knowledge of programming. The design of the software guarantees a high level of modularity where processing functions can be quickly replaced or concatenated. MassCascade is an open-source library for LC-MS data processing in metabolomics. It embraces the concept of visual programming through its KNIME plug-in, simplifying the process of building complex workflows. The library was validated using open data. PMID- 26279688 TI - The Importance of Radiopharmaceutical Chemistry for the Development of Nuclear Medicine: a Message from the Associate Editor. PMID- 26279689 TI - Future Perspectives of Radionanomedicine Using the Novel Micelle-Encapsulation Method for Surface Modification. AB - The emerging radionanomedicine has multifunctional and theranostic purposes. For these purposes, radionanomedicine should achieve the efficient and specific delivery of therapeutic agents by multifunctional characteristics, using low amounts of nanomaterials in vivo. Recent research on radiolabeled micelle encapsulated nanomaterials has been made on the their efficacy and safety using a one-step surface modification method (Jeong's method). This one-step multifunctional approach to the nanoparticle can be the important challenge in producing effective nanoplatforms for cancer imaging and therapy. PMID- 26279690 TI - Radioiodine Scan Index: A Simplified, Quantitative Treatment Response Parameter for Metastatic Thyroid Carcinoma. AB - PURPOSE: We aimed to develop and validate a simplified, novel quantification method for radioiodine whole-body scans (WBSs) as a predictor for the treatment response in differentiated thyroid carcinoma (DTC) patients with distant metastasis. METHODS: We retrospectively reviewed serial WBSs after radioiodine treatment from 2008 to 2011 in patients with metastatic DTC. For standardization of TSH simulation, only a subset of patients whose TSH level was fully enhanced (TSH > 80 mU/l) was enrolled. The radioiodine scan index (RSI) was calculated by the ratio of tumor-to-brain uptake. We compared correlations between the RSI and TSH-stimulated serum thyroglobulin (TSH_s_Tg) level and between the RSI and Tg reduction rate of consecutive radioiodine treatments. RESULTS: A total of 30 rounds of radioiodine treatment for 15 patients were eligible. Tumor histology was 11 papillary and 4 follicular subtypes. The TSH_s_Tg level was mean 980 ng/ml (range, 0.5-11,244). The Tg reduction rate after treatment was a mean of -7 % (range, -90 %-210 %). Mean RSI was 3.02 (range, 0.40-10.97). RSI was positively correlated with the TSH_s_Tg level (R(2) = 0.3084, p = 0.001) and negatively correlated with the Tg reduction rate (R(2) = 0.2993, p = 0.037). The regression equation to predict treatment response was as follows: Tg reduction rate = 14.581 * RSI + 51.183. CONCLUSIONS: Use of the radioiodine scan index derived from conventional WBS is feasible to reflect the serum Tg level in patients with metastatic DTC, and it may be useful for predicting the biologic treatment response after radioiodine treatment. PMID- 26279691 TI - Imaging Findings and Literature Review of (18)F-FDG PET/CT in Primary Systemic AL Amyloidosis. AB - PURPOSE: Although several case reports and case series have described (18)F-FDG PET/CT in amyloidosis, the value of (18)F-FDG PET/CT for diagnosing amyloidosis has not been clarified. We investigated the imaging findings of (18)F-FDG PET/CT in patients with primary systemic AL amyloidosis. METHODS: Subjects were 15 patients (M:F = 12:3; age, 61.5 +/- 7.4 years) with histologically confirmed primary systemic AL amyloidosis who underwent pretreatment (18)F-FDG PET/CT to rule out the possibility of malignancy or for initial workup of alleged cancer. For involved organs, visual and semiquantitative analyses were performed on (18)F FDG PET/CT images. In total, 22 organs (10 hearts, 5 kidneys, 2 stomachs, 2 colons, 1 ileum, 1 pancreas, and 1 liver) were histologically confirmed to have primary systemic AL amyloidosis. RESULTS: F-FDG uptake was significantly increased in 15 of the 22 organs (68.2 %; 10 hearts, 2 kidneys, 1 colon, 1 ileum, and 1 liver; SUVmax = 7.0 +/- 3.2, range 2.1-14.1). However, in 11 of 15 PET positive organs (78.6 %; 10 hearts and the ileum), it was difficult to differentiate pathological uptake from physiological uptake. Definitely abnormal (18)F-FDG uptake was found in only 4 of the 22 organs (18.2 %; 2 kidneys, 1 colon, and the liver). (18)F-FDG uptake was negative for pancreas and gastric lesions. CONCLUSIONS: Although (18)F-FDG PET/CT showed high uptake in two-thirds of the organs involving primary systemic AL amyloidosis, its sensitivity appeared to be low to make differentiation of pathological uptake from physiological uptake. However, due to the small number of cases, further study for the role of (18)F-FDG PET/CT in amyloidosis will be warranted. PMID- 26279692 TI - Evaluation of Selective Arterial Embolization Effect by Chitosan Micro-Hydrogels in Hindlimb Sarcoma Rodent Models Using Various Imaging Modalities. AB - PURPOSE: Embolization is mainly used to reduce the size of locally advanced tumors. In this study, selective arterial catheterization with chitosan micro hydrogels (CMH) into the femoral artery was performed and the therapeutic effect was validated using different imaging methods. METHODS: Male SD rats (n = 18, 6 weeks old) were randomly assigned into three groups: Group 1 as control, Group 2 without any ligation of distal femoral artery, and Group 3 with temporary ligation of the distal femoral artery. RR1022 sarcoma cell lines were inoculated into thigh muscle. After 1 week, CMH was injected into the proximal femoral artery. Different imaging modalities were performed during a 3-week follow-up. RESULTS: The tumor size was significantly (P < 0.001) decreased in both Group 2 and Group 3 (P < 0.001) after selective arterial embolization therapy. (18)F-FDG PET/CT revealed decreased intensity of (18)F-FDG uptake in tumors. The accumulation status of (125)I-CMH near the tumor was verified by gamma camera. CONCLUSIONS: Appropriate selective arterial embolization therapy with CMH was. PMID- 26279693 TI - Synthesis and Evaluation of (99m)Tc-Labeled Folate-Tripeptide Conjugate as a Folate Receptor-Targeted Imaging Agent in a Tumor-Bearing Mouse Model. AB - PURPOSE: The folate receptor (FR) is an attractive molecular target since it is overexpressed in a variety of human tumors. The purpose of the present study was to synthesize and evaluate the feasibility of a novel (99m)Tc-ECG-EDA (Glu-Cys Gly-ethylenediamine)-folate as an FR-positive tumor imaging agent in a mouse tumor model. MATERIALS AND METHODS: ECG-EDA-folate was synthesized using solid phase peptide synthesis (SPPS) and radiolabeled with (99m)Tc using tripeptide ECG as a chelator. FR-positive KB cells were inoculated in athymic nude mice. Following injection of (99m)Tc-ECG-EDA-folate, serial scintigraphy and micro SPECT/CT imaging were performed at various time points with and without pre administration of excess free folate. Mean count densities (MCD) for regions of interest drawn on KB tumors and major normal organs at each time point were measured, and uptake ratios of tumor to normal organs were calculated. RESULTS: ECG-EDA-folate was labeled with (99m)Tc with high radiolabeling efficiency and stability (>96 %). FR-positive tumors were clearly visualized on both scintigraphy and micro-SPECT/CT images and the tumor uptake of (99m)Tc-ECG-EDA folate was markedly suppressed with faint visualization of tumors by pre administration of excess free folate on serial planar scintigraphy, indicating FR specific binding of the agent. Furthermore, semiquantitative analysis of MCD data showed again that both tumor MCD and tumor-to-normal organ ratios decreased considerably by pre-administration of excess free folate, supporting FR-specific tumor uptake. Tumor-to-normal organ ratios approximately increased with time after injection until 4 h. CONCLUSION: The present study demonstrated that (99m)Tc-ECG-EDA-folate can bind specifically to FR with clear visualization of FR positive tumors in a mouse tumor model. PMID- 26279694 TI - Preparation and Evaluation of (68)Ga-ECC as a PET Renal Imaging Agent. AB - PURPOSE: Development of a gallium-68-labeled renal tracer can be a good substitute for Tc-99m, a known SPECT tracer. In this study, effort was made to develop (68)Ga-ethylenecysteamine cysteine ((68)Ga-ECC). METHODS: Ga-ECC was prepared using generator-based (68)GaCl3 and ethylenecysteamine cysteine (ECC) at optimized conditions. Stability of the complex was checked in human serum followed by partition coefficient determination of the tracer. The biodistribution of the tracer in rats was studied using tissue counting and PET/CT imaging up to 120 min. RESULTS: Ga-ECC was prepared at optimized conditions in 15 min at 90 degrees C (radiochemical purity ~97 +/- 0.88 % ITLC, >99 % HPLC, specific activity: 210 +/- 5 GBq/mM). (68)Ga-ECC was a water-soluble complex based on partition coefficient data (log P; -1.378) and was stable in the presence of human serum for 2 h at 37 degrees C. The biodistribution of the tracer demonstrated high kidney excretion of the tracer in 10-20 min. The SUVmax ratios of the liver to left kidney were 0.38 and 0.39 for 30 and 90 min, respectively, indicating high kidney uptake. CONCLUSION: Initial biodistribution results showed significant kidney and urinary excretion of the tracer comparable to that of the homologous (99m)Tc compound. The complex could be a possible PET kidney imaging agent with a fast imaging time. PMID- 26279695 TI - Papillary Thyroid Carcinoma Metastasis to the Lumbar Spine Masquerading as a Schmorl's Node. AB - A Schmorl's node is a common incidental finding encountered during radiologic imaging. Despite the vertebral body being a common site of metastatic disease, a lytic lesion adjacent to an endplate with typical imaging features can often confidently be called a Schmorl's node. This is a case report of a patient with a single well-defined FDG-avid papillary thyroid carcinoma metastasis to the spine that had imaging findings characteristic of a Schmorl's node on CT and MRI. This case is important to consider as it demonstrates that the imaging characteristics of metastatic disease and Schmorl's nodes can overlap. PMID- 26279696 TI - The Challenges of Treating Paraganglioma Patients with (177)Lu-DOTATATE PRRT: Catecholamine Crises, Tumor Lysis Syndrome and the Need for Modification of Treatment Protocols. AB - PURPOSE: A high percentage of paragangliomas express somatostatin receptors that can be utilized for targeted radioisotope therapy. The aim of this study was to describe and discuss the challenges of treating these tumors with (177)Lu [DOTA(0),Tyr(3)]octreotate (DOTATATE) radioisotope therapy using established protocols. METHODS AND RESULTS: Three paraganglioma patients were treated with 4 5 cycles of (177)Lu-DOTATATE and were evaluated for side effects and response to therapy. Two of the three patients developed severe adverse reactions following their first (177)Lu-DOTATATE treatment. One patient developed a catecholamine crisis and tumor lysis syndrome within hours of treatment, requiring intensive care unit (ICU) support, and another developed a catecholamine crisis 3 days after treatment, requiring hospitalization. The treatment protocols at our institution were subsequently modified by increasing the radioisotope infusion time from 15 to 30 min, as recommended in the literature, to 2-4 h and by reducing the administered dose of (177)Lu-DOTATATE. Subsequent (177)Lu-DOTATATE treatments utilizing the modified protocols were well tolerated, and response to therapy was achieved in all three patients, resulting in significantly improved quality of life. CONCLUSION: (177)Lu-DOTATATE is an exciting new therapeutic option in the management of paragangliomas; however, current treatment protocols described in the literature may need to be modified by lengthening the infusion time and/or lowering the initial treatment dose to prevent or reduce the severity of adverse reactions. PMID- 26279697 TI - Ga68-DOTA Peptide PET/CT to Detect Occult Mesenchymal Tumor-Inducing Osteomalacia: A Case Series of Three Patients. AB - Tumor-induced osteomalacia (TIO) is a rare disease that manifests with paraneoplasic syndrome and overproduction of fibroblast growth factor 23 (FGF23), leading to renal phosphate wasting and hyperphosphaturia, eventually leading to acquired hypophosphatemic osteomalacia. Diagnosis of this disease is often challenging because of the small size of the lesion, which can be localized in bone or soft tissue anywhere in the body. Detecting these occult mesenchymal tumors (OMT) is of great importance as they are potentially curable after tumor resection. The purpose of this case series is to provide some insight into the diagnosis and localization of OMT associated with osteomalacia, particularly using functional imaging with Ga68-DOTA peptide PET/CT scans. PMID- 26279698 TI - FDG-PET/CT in a Patient with Poor-Risk Non-Seminoma Testis with Mature Teratoma and Secondary Gliosarcoma: Multimodality Imaging for Guiding Multimodality Treatment. AB - The value of F-18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in detecting viable tumours in patients with metastasised non-seminomatous testicular cancer and residual and new masses post chemotherapy remains to be determined. We describe the case of a 41-year-old patient with metastasised non-seminomatous testicular cancer, with both retroperitoneal and extra-retroperitoneal residual masses post chemotherapy, for whom FDG-PET/CT guided major treatment decisions. FDG-PET/CT correctly identified the locations of viable tumour, as was proved by histology, and successfully guided surgery. In conclusion, in selected cases surveillance of patients with non-seminomatous testicular cancer with FDG-PET/CT can guide major treatment decisions when considering surgery for metastatic disease. PMID- 26279699 TI - Brain Metastasis from Neuroblastoma Depicted by (18)F-DOPA PET/CT. PMID- 26279700 TI - Single Pulmonary Langerhans Cell Histiocytosis Mimicking Metastasis in Lung Cancer: Imaging with (18)F-FDG PET/CT. PMID- 26279701 TI - A Rare Case of Isolated Pericardial Effusion Detected by SPECT/CT on a Post Therapeutic Radioiodine Whole-Body Scan. AB - We reported a rare finding of isolated pericardial uptake detected by SPECT/CT on posttherapeutic radioiodine whole body scan. This case highlights the usefulness of hybrid SPECT/CT, with subsequent correlation with biochemical results, in ruling out metastatic pericardial effusion in the postsurgical radioiodine remnant ablation setting. The effusion was resolved after reinstituted thyroid replacement therapy. Recombinant thyrotropin is recommended to avoid such rare but life-threatening complication. PMID- 26279702 TI - Influence of parameter values on the oscillation sensitivities of two p53-Mdm2 models. AB - Biomolecular networks that present oscillatory behavior are ubiquitous in nature. While some design principles for robust oscillations have been identified, it is not well understood how these oscillations are affected when the kinetic parameters are constantly changing or are not precisely known, as often occurs in cellular environments. Many models of diverse complexity level, for systems such as circadian rhythms, cell cycle or the p53 network, have been proposed. Here we assess the influence of hundreds of different parameter sets on the sensitivities of two configurations of a well-known oscillatory system, the p53 core network. We show that, for both models and all parameter sets, the parameter related to the p53 positive feedback, i.e. self-promotion, is the only one that presents sizeable sensitivities on extrema, periods and delay. Moreover, varying the parameter set values to change the dynamical characteristics of the response is more restricted in the simple model, whereas the complex model shows greater tunability. These results highlight the importance of the presence of specific network patterns, in addition to the role of parameter values, when we want to characterize oscillatory biochemical systems. PMID- 26279703 TI - Variation of swimming speed enhances the chemotactic migration of Escherichia coli. AB - Studies on chemotaxis of Escherichia coli have shown that modulation of tumble frequency causes a net drift up the gradient of attractants. Recently, it has been demonstrated that the bacteria is also capable of varying its runs speed in uniform concentration of attractant. In this study, we investigate the role of swimming speed on the chemotactic migration of bacteria. To this end, cells are exposed to gradients of a non-metabolizable analogue of glucose which are sensed via the Trg sensor. When exposed to a gradient, the cells modulate their tumble duration, which is accompanied with variation in swimming speed leading to drift velocities that are much higher than those achieved through the modulation of the tumble duration alone. We use an existing intra-cellular model developed for the Tar receptor and incorporate the variation of the swimming speed along with modulation of tumble frequency to predict drift velocities close to the measured values. The main implication of our study is that E. coli not only modulates the tumble frequency, but may also vary the swimming speed to affect chemotaxis and thereby efficiently sample its nutritionally rich environment. PMID- 26279704 TI - Knowledge-based discovery for designing CRISPR-CAS systems against invading mobilomes in thermophiles. AB - Clustered regularly interspaced short palindromic repeats (CRISPRs) are direct features of the prokaryotic genomes involved in resistance to their bacterial viruses and phages. Herein, we have identified CRISPR loci together with CRISPR associated sequences (CAS) genes to reveal their immunity against genome invaders in the thermophilic archaea and bacteria. Genomic survey of this study implied that genomic distribution of CRISPR-CAS systems was varied from strain to strain, which was determined by the degree of invading mobiloms. Direct repeats found to be equal in some extent in many thermopiles, but their spacers were differed in each strain. Phylogenetic analyses of CAS superfamily revealed that genes cmr, csh, csx11, HD domain, devR were belonged to the subtypes of cas gene family. The members in cas gene family of thermophiles were functionally diverged within closely related genomes and may contribute to develop several defense strategies. Nevertheless, genome dynamics, geological variation and host defense mechanism were contributed to share their molecular functions across the thermophiles. A thermophilic archaean, Thermococcus gammotolerans and thermophilic bacteria, Petrotoga mobilis and Thermotoga lettingae have shown superoperons-like appearance to cluster cas genes, which were typically evolved for their defense pathways. A cmr operon was identified with a specific promoter in a thermophilic archaean, Caldivirga maquilingensis. Overall, we concluded that knowledge-based genomic survey and phylogeny-based functional assignment have suggested for designing a reliable genetic regulatory circuit naturally from CRISPR-CAS systems, acquired defense pathways, to thermophiles in future synthetic biology. PMID- 26279705 TI - Quantification of the gene silencing performances of rationally-designed synthetic small RNAs. AB - Small RNAs (sRNAs) are genetic tools for the efficient and specific tuning of target genes expression in bacteria. Inspired by naturally occurring sRNAs, recent works proposed the use of artificial sRNAs in synthetic biology for predictable repression of the desired genes. Their potential was demonstrated in several application fields, such as metabolic engineering and bacterial physiology studies. Guidelines for the rational design of novel sRNAs have been recently proposed. According to these guidelines, in this work synthetic sRNAs were designed, constructed and quantitatively characterized in Escherichia coli. An sRNA targeting the reporter gene RFP was tested by measuring the specific gene silencing when RFP was expressed at different transcription levels, under the control of different promoters, in different strains, and in single-gene or operon architecture. The sRNA level was tuned by using plasmids maintained at different copy numbers. Results demonstrated that RFP silencing worked as expected in an sRNA and mRNA expression-dependent fashion. A mathematical model was used to support sRNA characterization and to estimate an efficiency-related parameter that can be used to compare the performance of the designed sRNA. Gene silencing was also successful when RFP was placed in a two-gene synthetic operon, while the non-target gene (GFP) in the operon was not considerably affected. Finally, silencing was evaluated for another designed sRNA targeting the endogenous lactate dehydrogenase gene. The quantitative study performed in this work elucidated interesting performance-related and context-dependent features of synthetic sRNAs that will strongly support predictable gene silencing in disparate basic or applied research studies. PMID- 26279706 TI - Design principles for robust oscillatory behavior. AB - Oscillatory responses are ubiquitous in regulatory networks of living organisms, a fact that has led to extensive efforts to study and replicate the circuits involved. However, to date, design principles that underlie the robustness of natural oscillators are not completely known. Here we study a three-component enzymatic network model in order to determine the topological requirements for robust oscillation. First, by simulating every possible topological arrangement and varying their parameter values, we demonstrate that robust oscillators can be obtained by augmenting the number of both negative feedback loops and positive autoregulations while maintaining an appropriate balance of positive and negative interactions. We then identify network motifs, whose presence in more complex topologies is a necessary condition for obtaining oscillatory responses. Finally, we pinpoint a series of simple architectural patterns that progressively render more robust oscillators. Together, these findings can help in the design of more reliable synthetic biomolecular networks and may also have implications in the understanding of other oscillatory systems. PMID- 26279707 TI - Marriage, Social Networks, and Health at Older Ages. PMID- 26279708 TI - The role of single instillation chemotherapy in patients who receive subsequent bacillus Calmette-Guerin: A retrospective single centre study, and systematic review of the literature. AB - INTRODUCTION: This retrospective study was undertaken to evaluate the combined effect of immediate intravesical chemotherapy and subsequent bacillus Calmette Guerin (BCG) therapy. METHODS: The study population consisted of 207 intermediate or high-risk patients with non-muscle invasive bladder cancer who underwent an induction course of BCG between 1993 and 2007. We introduced single immediate instillation of 50 mg epirubicin for all cases in 2004, and thus earlier cases could be considered as historical controls. The primary endpoint was recurrence free survival (RFS). For cumulative analysis, we systematically reviewed studies indexed in databases. Including ours, the records of 856 patients from a total of 7 studies, including ours, were finally analyzed. RESULTS: In our cohort, the 5 year RFS in patients who received the combination therapy was 66.2%, compared to 55.2% in the BCG alone group (p = 0.149). Multivariate analysis on tumour recurrence showed that patients with the combination therapy had a hazard ratio (HR) of 0.74 (p = 0.189). A subsequent literature review revealed that RFS rates in the combination groups were higher than those in the corresponding BCG alone groups in 4/7 studies (p = 0.02-0.15), and lower in 1 study (p = 0.51). We identified 5 studies which examined a HR for combination therapy, and performed a cumulative analysis. Adding a single chemo-instillation prior to BCG resulted in a significant reduction in tumour recurrence (summary HR 0.69, p = 0.010). CONCLUSIONS: Our analysis suggested that the combination of single chemo instillation with subsequent BCG therapy exhibited an additive effect against potential tumour recurrence. PMID- 26279709 TI - Factors predicting prolonged operative time for individual surgical steps of robot-assisted radical prostatectomy (RARP): A single surgeon's experience. AB - INTRODUCTION: We evaluated the average time required to complete individual steps of robotic-assisted radical prostatectomy (RARP) by an expert RARP surgeon. The intent is to help establish a time-based benchmark to aim for during apprenticeship. In addition, we aimed to evaluate preoperative patient factors, which could prolong the operative time of these individual steps. METHODS: We retrospectively identified 247 patients who underwent RARP, performed by an experienced robotic surgeon at our institution. Baseline patient characteristics and the duration of each step were recorded. Multivariate analysis was performed to predict factors of prolonged individual steps. RESULTS: In multivariable analysis, obesity was a significant predictor of prolonged operative time of: docking (odds ratio [OR] 1.96), urethral division (OR 3.13), and vesico-urethral anastomosis (VUA) (OR 2.63). Prostate volume was also a significant predictor of longer operative time in dorsal vein complex ligation (OR 1.02), bladder neck division (OR 1.03), pedicle control (OR 1.04), urethral division (OR 1.02), and VUA (OR 1.03). A prolonged bladder neck division was predicted by the presence of a median lobe (OR 5.03). Only obesity (OR 2.56) and prostate volume (OR 1.04) were predictors of a longer overall operative time. CONCLUSIONS: Obesity and prostate volume are powerful predictors of longer overall operative time. Furthermore, both can predict prolonged time of several individual RARP steps. The presence of a median lobe is a strong predictor of a longer bladder neck division. These factors should be taken into consideration during RARP training. PMID- 26279710 TI - Sexual function after surgical treatment for penile cancer: Which organ-sparing approach gives the best results? AB - INTRODUCTION: We compared the postoperative sexual function of patients who underwent wide local excision (WLE) and glansectomy with urethral glanduloplasty for penile cancer. METHODS: We retrospectively reviewed clinical data of 41 patients affected by superficial, localized penile cancer (<=cT2a) between 2006 and 2013. Patients with severe erectile dysfunction and not interested in resuming an active sexual life were selected for penile partial amputation. Patients with preoperative satisfying erectile function and concerned about the preservation of their sexual potency were scheduled for WLE (Group A) or glansectomy with urethral glanduloplasty (Group B). Sexual function was assessed with the International Index of Erectile Function (IIEF) questionnaire and the Sex Encounter Profile (SEP). At 1 year, patients were asked to complete the questionnaires again and were questioned about their genital sensibility and ejaculatory reflex persistence. Postoperative complications were reported according to the Clavien-Dindo classification. Statistical analysis was performed by two-tailed test: Student t-test and chi-square. RESULTS: Among the 41 patients enrolled, 12 underwent WLE (29.2%), 23 glansectomy with urethral glanduloplasty (56%) and 6 with penile partial amputation (14.6%). A decrease in postoperative IIEF was recorded in both groups, but was statistically significant only in Group B (p = 0.003). As for the SEP, while no significant changes were recorded postoperatively in Group A, a marked reduction was reported for Group B, with a statistically significant decrease in the possibility of achieving penetrative intercourse (p = 0.006) and in the perceived satisfaction during sexual activity (p = 0.004). CONCLUSIONS: WLE lead to better sexual outcomes and less postoperative complications as compared to glansectomy with urethral glanduloplasty. PMID- 26279711 TI - The relative contribution of urine extravasation to elevate plasma creatinine levels in acute unilateral ureteral obstruction. AB - INTRODUCTION: Rising levels of plasma creatinine in the setting of acute unilateral ureteral obstruction (AUUO) often reflects acute renal failure, mandating kidney drainage. We hypothesize that re-absorption of peri-renal urine extravasation (PUE), a common result of UUO, contributes significantly to the elevation in plasma creatinine, rendering the latter an inaccurate benchmark for renal function. We explored this hypothesis in a rat model of AUUO and PUE. METHODS: In total, 20 rats were equally divided into 4 groups. Groups 1 and 2 underwent unilateral ligation of the ureter with infiltration of rat's urine (index group) or saline (control) into the peri-renal space. Two additional control groups underwent peri-renal injection of either urine or saline without AUUO. Plasma creatinine levels were determined immediately prior to the procedure (T0), and hourly for 3 hours (T1, T2 and T3). Renal histology was investigated after 3 hours. RESULTS: Rats in the index group had a significantly greater increase in plasma creatinine levels over 3 hours compared to all other groups (p < 0.05). At T3, average plasma creatinine levels for the index group increased by 96% (0.49 +/- 0.18 mg/dL) compared to 46% (0.23 +/- 0.06 mg/dL increase) in the AUUO and saline group, and less than 15% rise in both the non-obstructed control groups. Our study limitations includes lack of spontaneous PUE and intraperitoneal surgical approach. CONCLUSIONS: Absorption of peri-renal urine in the presence of AUUO is a significant contributor to rising plasma creatinine levels, beyond those attributable to the obstruction alone, and may overestimate the extent of the true renal functional impairment. PMID- 26279712 TI - Prevalence and risk factors of contralateral extraprostatic extension in men undergoing radical prostatectomy for unilateral disease at biopsy: A global multi institutional experience. AB - INTRODUCTION: We assessed the incidence of contralateral prostate cancer (cPCa), contralateral EPE (cEPE) and contralateral positive surgical margins (cPSM) in patients diagnosed preoperatively with unilateral prostate cancer and evaluated risk factors predictive of contralateral disease extension. METHODS: The occurrence of cPCa, cEPE and cPSM and the side-specific nerve-sparing technique performed were collected postoperatively from 327 men diagnosed with unilateral prostate cancer at biopsy. Parameters, such as the localization, proportion, and percentage of cancer in positive cores, were prospectively collected. RESULTS: Overall, 50.5% of patients had bilateral disease, and were at higher risk when associated with a positive biopsy core at the apex (p = 0.016). The overall incidence of ipsilateral EPE and cEPE were 21.4% and 3.4%, respectively (p < 0.001). Compared to cPCa, ipsilateral disease was at an almost 4-fold higher risk of extending out of the prostate (p < 0.001). None of the criteria tested were identified as useful predictors for cEPE. The low incidence of cEPE in our cohort could limit our ability to detect significance. The overall incidence of ipsilateral PSM and cPSM were 15.3% and 5.8%, respectively (p < 0.001). More aggressive nerve-sparing was not associated with a higher incidence of PSM. Prostate sides selected for more aggressive nerve-sparing were associated with younger patients (p < 0.001), a smaller prostate (p = 0.006), and a lower percentage of cancer in biopsy material (p = 0.008). CONCLUSION: Although the risk of cPCa is high in patients diagnosed with unilateral prostate cancer at biopsy, the risk of cEPE and cPSM is low, yet not insignificant. Contralateral aggressive nerve-sparing should be used with caution and should not compromise oncological outcome. PMID- 26279713 TI - Few modifiable factors predict readmission following radical cystectomy. AB - INTRODUCTION: We sought to determine the patient and provider-related factors associated with readmission after radical cystectomy (RC) for bladder cancer. In this era of healthcare reform, hospital performance measures, such as readmission, are beginning to affect provider reimbursement. Given its high readmission rate, RC could be a target for quality improvement. METHODS: We reviewed bladder cancer patients who underwent RC in California's State Inpatient Database (2005-2009) of the Healthcare Cost and Utilization Project. We examined patient-(e.g., race, discharge disposition) and provider-related factors (e.g., volume) and evaluated their association with 30-day readmission. Multivariable logistic regression was used to examine associations of interest. RESULTS: Overall, 22.8% (n = 833) of the 3649 patients who underwent RC were readmitted within 30 days. Regarding disposition, 34.8%, 50.8%, and 12.2% were discharged home, home with home healthcare, and to a post-acute care facility (PACF), respectively. Within 30 days, 20.3%, 20.9%, and 42.3% were discharged home, home with home healthcare, and to a PACF were readmitted, respectively. African Americans (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.07-2.50), having >=2 comorbidities (OR 1.42, 95% CI 1.06-1.91), receiving a neobladder (OR 1.45, 95% CI 1.09-1.93), and discharged to a PACF (OR 3.79, 95% CI 2.88-4.98) were independent factors associated with readmission. Hospital stays >=15 days were associated with less readmission (OR 0.43, 95% CI 0.27-0.67, p = 0.0002). Procedure volume was not associated with complication, in-hospital mortality, or readmission. CONCLUSIONS: About one-fifth of patients undergoing RC are readmitted. Patients who are discharged to a PACF, African American, and who have more extensive comorbidities tend to experience more readmissions. Increased efforts with care coordination among these patients may help reduce readmissions. PMID- 26279714 TI - A report on the clinical efficacy of a new Bougie-internal urethrectomy. AB - INTRODUCTION: We compare the clinical efficacy of the new bougie-internal urethrectomy (BIU) with internal urethrotomy and urethroplasty to treat urethral stricture disease. METHODS: We prospectively studied 186 people with urethral stricture disease. Of these, 84 were identified for urethroplasty and 102 for internal urethrotomy (endoscopic urethrotomy). Among the 84 identified for urethroplasty, 52 received BIU (Group 1) and the remaining 32 received urethroplasty. Among the 102 identified for internal urethrotomy, 58 received BIU (Group 2) and the remaining 44 received the internal urethrotomy. After surgery, we evaluated the clinical efficacy of the BIU (operative invasions, voiding flow rates, complications, sequelae) compared with the endoscopic treatment and urethroplasty. RESULTS: Patient age ranged from 20 to 70 years. The follow-up period was 2 years. In the BIU Group 1, the BIU Group 2, and the internal urethrotomy (endoscopic treatment), the length of strictures were 2.9 +/- 1.5, 2.8 +/- 1.3, 1.6 +/- 0.7, and 1.5 +/- 0.6, respectively. In the BIU Group 1, the urethroplasty, the BIU Group 2, and the internal urethrotomy (endoscopic treatment), the amount of bleeding was 34.1 +/- 17.1, 172.2 +/- 29.8, 28.5 +/- 9.8, and 49.7 +/- 13.6 mL, respectively. In the BIU Group 1, the urethroplasty, the BIU Group 2, and the internal urethrotomy, the recurrence rates were 5.8%, 86%, 6.8% and 25%, and the average flow rates were 18.1 +/- 4.8, 13.1 +/- 3.9, 18.2 +/- 3.6, 10.1 +/- 3.1 mL/s, respectively. There was no sequealae (sexual dysfunction, penile change) in both BIU groups. CONCLUSIONS: The new BIU could be considered first-line treatment in all patients with indications for visual internal urethrotomy and urethroplasty. PMID- 26279715 TI - Impact of drainage technique on pediatric pyeloplasty: Comparative analysis of externalized uretero-pyelostomy versus double-J internal stents. AB - INTRODUCTION: Pediatric pyeloplasty with double J (DJ) stent drainage requires manipulation of the uretero-vesical junction (UVJ) and a second anesthetic for removal. Externalized uretero-pyelostomy (EUP) stents avoid these issues. We report outcomes of laparoscopic and open pyeloplasty with EUP compared to DJ stents in children. METHODS: We retrospectively reviewed 76 consecutive children who underwent pyeloplasty for ureteropelvic junction (UPJ) obstruction over a 1 year period by 5 pediatric urologists at a single institution. The exclusion criteria included patients with concomitant urological procedures, other urinary drainage strategies, "stentless" pyeloplasty or patients without follow-up data. Based on surgeon preference, 24 patients had a EUP stent and 38 had a DJ stent placed. RESULTS: The mean follow-up was 23.8 +/- 10.9 months and 21.1 +/- 11.1 months for the EUP and DJ stent groups, respectively (p = 0.32). The mean age was 40 +/- 54 months and 80 +/- 78 months for the EUP and DJ groups, respectively (p = 0.04). The EUP group had a greater proportion of open pyeloplasties (n = 17, 71%) versus the DJ group (n = 16, 42%; p = 0.04). There were no statistically significant differences in operative time, length of stay, and overall complication rate between groups. Complications were divided by timing of complication (intraoperative, before and after 3 months) and according to the Clavien Classification system. There were no statistically significant differences between these subgroups. The limitations of this study include small sample size, potential selection bias, and heterogeneity between both study groups. CONCLUSIONS: Pyeloplasty using EUP stents does not incur prolonged operative time, longer length of stay or higher complication rate when compared to DJ stents. Within the limitations of this study, EUP stents may be a safe alternative to DJ stents. PMID- 26279716 TI - [Not Available]. PMID- 26279717 TI - A critical review of recent clinical practice guidelines on the diagnosis and treatment of non-neurogenic male lower urinary tract symptoms. AB - INTRODUCTION: We provide an overview of the quality of recent clinical clinical practice guidelines (CPGs) for non-neurogenic male lower urinary tract symptoms (LUTS) and summarize the recommendations for their diagnosis, assessment, and treatment. METHODS: We systematically searched recent (2008-2013) CPGs for non neurogenic male LUTS. Eligible CPGs were assessed and appraised using Appraisal of Guidelines, Research and Evaluation II (AGREE II) tool by a CPG-appraisal group. The appraisal scores for each guideline were summarized according to each domain and in total. A recommendation summary was made across the guidelines for diagnostics, conservative management, medical, minimally invasive therapy, and surgical management. RESULTS: A total of 8 guidelines were considered. According to AGREE II appraisal of guidelines, the National Institute for Health and Clinical Excellence (NICE), American Urological Association (AUA) and European Association of Urology (EAU) consistently scored high on the guideline domains assessed. Recommendations on diagnostics, conservative management, medical, and surgical management were consistent among the top 3 guidelines. However, we noted a discrepancy in recommending minimally invasive therapy as an alternative management of moderate to severe or bothersome non-neurogenic male LUTS secondary to benign prostatic enlargement (BPE); the NICE guideline, in particular, does not recommend using minimally invasive therapy. CONCLUSION: The quality of recent CPGs on non-neurogenic male LUTS was appraised and summarized. The guidelines from NICE, AUA and EAU were considered highly compliant to the AGREE II proposition for guideline formation and development. PMID- 26279718 TI - [Not Available]. PMID- 26279719 TI - Experience with sliding-clip splenorrhaphy for splenic injury during radical nephrectomy. AB - INTRODUCTION: We report our experience with sliding-clip splenorrhaphy (SCS), a novel splenic conservation technique, for iatrogenic splenic injury (ISI) during a left radical nephrectomy (RN). We also reviewed the literature on ISI. METHODS: We retrospectively reviewed data from patients who had RN between January 2005 and December 2013 at our institution. The technique used was similar to sliding clip renorrhaphy. Our Medline literature identified articles containing "splenic injury during nephrectomy," "iatrogenic splenic injury." "iatrogenic splenectomy," and "splenorrhaphy." Our primary outcome measures included incidence of splenic injury and splenic conservation rate and splenectomy. RESULTS: Among the 370 RN, 140 were left sided. ISI injury occurred in 6 left RN (incidence 1.6% for all nephrectomies, 4.2% for left-sided nephrectomies). All 6 cases had open procedure and for the left-sided procedure. Splenic conservation was attempted in 4 patients using SCS and 3 out of 4 were successfully repaired. Altogether 3 patients had splenectomy (incidence 0.8% for all nephrectomies, 2.1% for left-sided nephrectomies). Our literature review revealed that the incidence of iatrogenic splenectomy during left nephrectomy varies from 1.3% to 13.2%. CONCLUSIONS: SCS is an acceptable novel splenic conservation technique due to its ease of use and success in selected patients with ISI. There is little evidence on the true incidence of ISI especially on splenic conservation during nephrectomy. Every attempt at splenic conservation is likely to improve immediate and long-term patient outcomes. PMID- 26279720 TI - Emphysematous pyelonephritis: Our experience in managing these cases. AB - INTRODUCTION: Emphysematous pyelonephritis (EPN) is a rare acute necrotising infection of renal parenchyma. We discuss clinical details and treatment strategies of 8 patients with EPN followed at our clinic. METHODS: We retrospectively reviewed the clinical, laboratory, radiological findings and treatment modalities of 8 patients with EPN followed at our urology clinic between 2012 and 2015. RESULTS: The mean patient age (female: 5; male: 3) was 62 (range: 51-82) years. Based on computed tomographic findings, EPN was classified as class 1 (n = 3), class 2 (n = 3) and class 3a (n = 2). All patients had fever, flank pain, nausea, and vomiting. Five patients had type 2 diabetes mellitus and 3 diabetic patients also had renal stones. Escherichia coli (n = 6), Klebsiella species (n = 1), and Proteus species (n = 1) were grown in urine cultures. All patients had unilateral involvement. Increased white blood cell counts, sedimentation rate, and C-reactive protein levels were detected in all cases. In addition to medical treatment, 2 patients underwent a nephrostomy catheter placement and another 2 patients underwent nephrectomy upon deterioration of her general health state. After achieving clinical stabilization with medical treatment, 1 patient underwent endoscopic ureteral stone treatment. The remaining 3 cases were treated only with antibiotherapy. All patients were discharged with clinical cure. CONCLUSION: Mortality rates of EPN are gradually decreasing. Preservation of renal reserve is possible due to early diagnosis, appropriate antibiotherapy, and drainage. PMID- 26279721 TI - Genitourinary tuberculosis in North America: A rare clinical entity. AB - INTRODUCTION: Although tuberculosis (TB) is the most common cause of mortality from infectious diseases worldwide, genitourinary TB in North America is rare. We review 3 cases of genitourinary TB diagnosed within the last 5 years. CASES: The first case is that of a 76-year-old African-Canadian woman who was referred for percutaneous nephrolithotomy of right lower pole renal stones. Although renal TB was suspected, her initial urinary TB culture was negative. On follow-up imaging, she developed bilateral ureteral thickening and ureteroscopic biopsy confirmed necrotizing granulomata. Repeat urine cultures were positive for M. tuberculosis. The second case is a 73-year-old Italian-Canadian woman who was referred for ureteroscopic biopsy of left thickened ureter to rule out urothelial carcinoma. Initial urine TB cultures were negative, despite biopsies confirming granulomatous inflammation. She was closely followed with urine cytologies and TB cultures. Repeat urine culture was positive for M. tuberculosis. Both patients were treated with a course of anti-tuberculous agents and indwelling ureteral stents to relieve ureteral obstruction. The third case is a 70-year-old Cree woman who was referred for percutaneous nephrolithotomy of a left "staghorn stone" in an atrophic left kidney. Thirty years earlier she had been treated for pulmonary TB in addition to ileocystoplasty for a "thimble" bladder. A computed tomography scan showed autonephrectomized left kidney. Her urine TB cultures were negative. She was placed on prophylactic antibiotics for her recurrent bacterial urinary tract infections. CONCLUSION: Genitourinary TB may present in various subtle ways, and the astute clinician must have a high index of suspicion for this disease in patients with atypical clinical and radiologic findings. In addition, TB urine cultures should be repeated when there is high index of suspicion. PMID- 26279722 TI - Technical feasibility of robot-assisted laparoscopic radical prostatectomy in renal transplant recipients: Results of a series of 12 consecutive cases. AB - INTRODUCTION: We evaluate the technical feasibility of robotic prostatectomy in renal transplant recipients. METHODS: We retrospectively analyzed preoperative and perioperative settings, as well as functional and oncologic results of 12 patients operated on between 2009 and 2013. Prostatectomy was performed via a transperitoneal approach without any changing in the ports position. The average age was 61.92 +/- 2.98 years. The period between transplant and the diagnosis of adenocarcinoma was 79.7 months. The mean PSA was 7.34 ng/mL (range: 4.9-11). RESULTS: The operative time was 241.3 +/- 35.6 minutes with only one conversion and one transfusion. The intervention was difficult due to adhesions on the side of the graft in 50% of cases. There was a case of obstructive acute renal failure resulting from a hematoma of the Retzius treated by percutaneous nephrostomy at D20. There was a majority of pT2c (72.7%), including 3 positive margins (27.3%) and 2 biochemical relapses treated with radiotherapy and hormonotherapy, respectively. The end point prostate-specific antigen was undetectable. There was no significant difference between preoperative and J7 creatinine (p = 0. 22). CONCLUSIONS: Robotic prostatectomy in renal transplant recipients is a safe technique with no serious effects on the allograft. PMID- 26279723 TI - Prone split-leg position to manage encrusted ureteral stents in a single-stage procedure in women: Step-by-step surgical technique. AB - The management of encrusted ureteral stents is costly, time consuming and may be risky for the patient and challenging for the urologist. Treatment modalities for encrusted stents include extracorporeal shock wave lithotripsy, cystolithopaxy, rigid or flexible ureteroscopy with intracorporeal lithotripsy, percutaneous nephrolithotomy, open surgery, and a combination of those methods. In this study we describe the management of severe forgotten encrusted ureteral stents in 3 female patients using a prone split-leg position. This position allows us to effectively treat any site and degree of stent encrustation in a single-session approach with the patient in the same position during the whole procedure. All patients were rendered stent and stone free. No complications occurred. PMID- 26279724 TI - Feasibility and safety of radical cystectomy under combined spinal and epidural anesthesia in octogenarian patients with ASA score >=3: A case series. AB - INTRODUCTION: This study evaluated the feasibility and safety of open radical cystectomy (RC) under combined regional anesthesia (CRA) in high-risk octogenarian patients. METHODS: We retrospectively evaluated the medical records of high-risk, octogenarian bladder cancer patients submitted to open RC with CRA. Demographic and clinical data, intraoperative parameters and perioperative and postoperative complications were recorded using the Clavien-Dindo classification. RESULTS: In total, 14 male and 4 female patients, with a median age of 82.5 years were enrolled. Ureterocutaneostomy was performed in 15 patients and Bricker ileal conduit in the remaining 3. Operative time ranged from 97 to 184 minutes. Five patients were transfused and no major intraoperative complications occurred. Postoperative complications 30 days later included ileus (Grade II) in 3 patients, surgical trauma infection in 1 patient (Grade II), respiratory infection in 2 patients (Grade III), and hydronephrosis with concurrent urinary tract infection in 3 patients (Grade III). No deaths occurred. CONCLUSIONS: Our study showed that octogenarian, high-risk bladder cancer patients with indications for RC can safely undergo the surgical procedure under CRA, without apparent increase in major complications. PMID- 26279725 TI - Localized prostate cancer presenting as a renal pseudo-tumour. AB - Malignant obstructive uropathy can be a result of common genitourinary malignancies (i.e., ureter, prostate, bladder, or kidney) or extrinsic processes, such as colon and ovarian tumours. We present a case of uropathy caused by prostatic obstruction, which initially presented as a renal psuedo-tumour. We also review the relevant literature. PMID- 26279726 TI - Composite renal cell carcinoma and angiomyolipoma in a patient with Tuberous sclerosis: A diagnostic dilemma. AB - Tuberous sclerosis (TS) is an autosomal dominant disorder associated with various renal pathologies, including angiomyolipoma (AML). Renal cell carcinoma (RCC) with concomitant AML is rare. We report a case of composite RCC and AML in a young male with TS. This 25-year-old male presented with an abdominal mass. The abdominal computed tomography scan revealed RCC in the left kidney and AML in right kidney. A left radical nephrectomy was performed. Microscopy showed a tumour composed of closely intermingled RCC and AML components. Immunohistochemistry was performed for confirmation. A diagnosis of composite tumour with clear cell RCC and AML was made. Though the coexistence of RCC with AML is rare, and the composite variant is even rarer, one must be aware of this entity to prevent misdiagnosis as well as upstaging of RCC, and also to avoid missing areas of RCC within a large AML, especially in TS patients. PMID- 26279727 TI - Endourological treatment of bilateral ureteral stones in bilateral ureteral duplication with right ureterocele. AB - Bilateral collecting system duplication is a very rare abnormality, including the splitting of the ureteric bud. Complete ureteral duplication with two separate openings in the urinary bladder is also extremely rare. To the best of our knowledge, we present the first case of bilateral ureteral stones in bilateral duplicated collecting system. PMID- 26279728 TI - Bladder leiomyosarcoma in a patient with chronic ketamine abuse: A case report. AB - Bladder leiomyosarcoma is a rare mesenchymal tumour, accounting for less than 0.5% of all primary bladder malignancies. Adult women of reproductive age have the higher incidence of bladder leiomyosarcoma. Exposure to local pelvic radiotherapy or systemic chemotherapy, especially cyclophosphamide therapy, is also a significant risk factor. We describe a case of a 31-year-old male who developed urinary bladder leiomyosarcoma. The patient had no history of radiotherapy, systemic chemotherapy, or other significant event, except a 5-year history of ketamine abuse. The tumour was found on the left bladder wall and was definitively diagnosed by transurethral resection of the bladder tumour. A partial cystectomy was performed. There are no known reports of urinary bladder leiomyosarcoma associated with chronic ketamine abuse; therefore, we speculate that chronic ketamine abuse may be a factor in the development of this infrequent bladder malignancy. PMID- 26279729 TI - Renal vein leiomyosarcoma and renal cell carcinoma presenting together: A case report and discussion on the follow-up. AB - Leiomyosarcoma affecting the renal vein is rare, with about 30 documented cases in the English literature. The appearance on computed tomography can be difficult to interpret and is often confused with advanced renal cell carcinoma (RCC). This confusion can have implications on the perioperative care of patients presenting with this disease. We report a case with an usual radiological appearance of a renal vein leiomyosarcoma, alongside a separate RCC. This case highlights the need for a high index of suspicion in radiological reporting and provides a dilemma in regards to postoperative surveillance. PMID- 26279730 TI - Laparoscopic simple nephrectomy patient with situs inversus totalis and left renal hypoplasia: A case report. AB - Situs inversus totalis (SIT) is a relatively rare anatomical condition characterized by the transposition of thoracic and abdominal organs from the normal side to the opposite position. Most reports of laparoscopic procedures in patients with SIT cite technical difficulties and longer operative times due to disorientation because of the reversed abdominal organs and necessary modification of the surgeon's movements and techniques. We present a case of a patient with SIT in whom a transperitoneal laparoscopic simple nephrectomy was performed. PMID- 26279731 TI - Coincident detection of lung metastasis of prostate cancer and primary lung cancer: A case report. AB - We report an extremely rare case of 79-year-old man, who was discovered with coincidental lung metastasis of prostate cancer and primary lung cancer. The patient presented with low prostate-specific antigen and two lung lesions: one in the right lower lobe, and one in the right upper lobe, 3 years after he was treated with external beam radiotherapy for Gleason score 4+3=7, cT3aN0M0 prostate cancer. A computed tomography-guided needle biopsy of a nodule in the right lower lobe revealed suspicious metastasis of prostate cancer. Thoracoscopic excisions of both lesions were performed, and each lung lesion was diagnosed as being metastatic prostate cancer and primary lung cancer. PMID- 26279732 TI - Liposarcoma of the spermatic cord: A case report. AB - Spermatic cord liposarcoma is very rare and characterized by a painless inguinal or scrotal mass. This is a case report of a 66-year-old man presenting with a mass in his left scrotum. Inguinal orchiectomy was performed and the histopathological examination revealed a liposarcoma of the spermatic cord. PMID- 26279733 TI - Spontaneous rupture of adult Wilms' tumor: A case report and review of the literature. AB - Wilms' tumour is rare in adults, and spontaneous rupture with retroperitoneal hemorrhage as the presenting sign of renal tumour is also uncommon. We present a case of a 20-year-old woman with spontaneous rupture of Wilms' tumour by describing the course of diagnosis and treatment. The patient underwent an open left radical nephrectomy, and was treated with 18 weeks of adjuvant chemotherapy with vincristine and actinomycin D. The follow-up of 12 months demonstrated no recurrence. We also reviewed the limited number of related reports. These suggest that the preoperative diagnosis of adult Wilms' tumour is very difficult, and radical nephrectomy and postoperative comprehensive therapy are equally important in the treatment of these patients. Factors of prognosis for adults with Wilms' tumour include tumour stage, histopathology, and time and type of therapy. PMID- 26279734 TI - It's not always varicocele: A strange case of Zinner syndrome. AB - A 42-year-old man presented with a huge varicocele. The patient was completely asymptomatic and he did not complain of dysuria, perineal discomfort, or ejaculatory pain. During the visit, the mass mimicked a varicocele and during the Valsalva maneuver a reflux was documented by colour Doppler ultrasound and an abdominal ultrasound revealed an agenesis of the right kidney and a 4.5-cm diameter intra-prostatic cyst. An abdominal and pelvis magnetic resonance imaging was then performed, which confirmed the right renal agenesis, with an epididymal enlargement in the body and tail. This is a unique case of Zinner syndrome in which the patient presented with a paratesticular mass mimicking a varicocele. PMID- 26279735 TI - Incidental retroperitoneal paraganglioma in patient candidate to radical prostatectomy: Concurrent surgical treatments by robotic approach. AB - We report a case of a 75-year-old male with biopsy-proven prostate cancer and candidate for radical prostatectomy. The patient's medical history includes hypertension and atrial fibrillation in prophylactic treatment; however, he was suffering from recurrent paroxysmal episodes of supraventricular tachycardia. Abdominal magnetic resonance performed for prostate cancer staging detected a non lymphatic inter-cavo-aortic mass of 42 * 37 * 43 cm. Results of biochemical screening confirmed the clinical diagnosis of symptomatic paraganglioma. The patient was subjected in a single robotic session for concurrent excision of the inter-aortocaval mass and radical prostatectomy with bilateral pelvic lymph-node dissection. During the procedure, there were no anesthesiological or surgical complications. The postoperative course was uneventful and the patient was discharged on postoperative day 5. Six months after surgery, his prostate specific antigen level was undetectable and the abdominal magnetic resonance imaging was negative for local recurrence or metastasis of paraganglioma. No more episodes of tachycardia were reported or antihypertensive therapy was necessary. PMID- 26279736 TI - Malignant epitheloid angiomyolipoma of the kidney in a child treated with sunitinib, everolimus and axitinib. AB - The malignant variant of epithelioid angiomyolipoma (EAML) of the kidney is uncommon, extremely aggressive and behaves like a renal cell carcinoma. We present a case of a 12-year-old male with malignant EAML who was treated according to adult treatment protocols. To our knowledge, axitinib has not been used before in children. We conclude that adult protocols, in this rare case, could be safely used in rare childhood malignancies. PMID- 26279737 TI - Computationally efficient confidence intervals for cross-validated area under the ROC curve estimates. AB - In binary classification problems, the area under the ROC curve (AUC) is commonly used to evaluate the performance of a prediction model. Often, it is combined with cross-validation in order to assess how the results will generalize to an independent data set. In order to evaluate the quality of an estimate for cross validated AUC, we obtain an estimate of its variance. For massive data sets, the process of generating a single performance estimate can be computationally expensive. Additionally, when using a complex prediction method, the process of cross-validating a predictive model on even a relatively small data set can still require a large amount of computation time. Thus, in many practical settings, the bootstrap is a computationally intractable approach to variance estimation. As an alternative to the bootstrap, we demonstrate a computationally efficient influence curve based approach to obtaining a variance estimate for cross validated AUC. PMID- 26279738 TI - Risk Behaviors Among Suburban Women who Use Methamphetamine: Social Harms and Social Solutions. AB - We propose that female methamphetamine users who live in suburbia experience risks for disease transmission stemming from their social environment that remain under the radar of public health surveillance networks. The data analyzed in this paper were collected from 2007 to 2011 and were drawn from two sequential studies on methamphetamine use. The studies were conducted in the suburbs of a southeastern United States metropolis. We analyzed a total of 65 qualitative interviews with former and active methamphetamine-using women. Data from focus groups also were included in the analysis. The participants' ages ranged from 18 to 51 years. We identified three major themes with regards to risk behaviors and transmission of infectious diseases: (1) setting risk behaviors, such as sharing syringes and homelessness, lack of transportation and unemployment; (2) sexual risk behaviors such as condom use and having multiple partners; and (3) service- related risks, such as risk awareness and prevention behaviors as well as utilization of social services and healthcare. Our findings point to the pervasive nature of social influences on the risk for infectious disease transmission. We suggest that harm reduction programs be implemented in suburban communities to increase access to these services. Secondly, our data support the concept of social recovery for drug users to better their health and social lives holistically. PMID- 26279740 TI - Spontaneous Arterial Hemorrhage of the Hand Resulting in Compartment Syndrome. PMID- 26279739 TI - Cody. AB - Advances in burn management over the past 2 decades have resulted in improved survival and reduced morbidity. The treatment of a single patient following a 90% total body surface area injury illustrates the intensity of labour and coordinated hospital care required for such catastrophically injured patients. Data were extracted from the medical records and from personal recollections of the individual members of the multidisciplinary team as well as from the patient. The clinical course and management of complications are described chronologically as a series of overlapping phases from admission to discharge. PMID- 26279741 TI - Leech (Hirudo medicinalis) Therapy for the Treatment of Nipple-Areolar Complex Congestion Following Breast Reduction. PMID- 26279742 TI - Estimating beta-mixing coefficients. AB - The literature on statistical learning for time series assumes the asymptotic independence or "mixing" of the data-generating process. These mixing assumptions are never tested, and there are no methods for estimating mixing rates from data. We give an estimator for the beta-mixing rate based on a single stationary sample path and show it is L1-risk consistent. PMID- 26279743 TI - Mixed LICORS: A Nonparametric Algorithm for Predictive State Reconstruction. AB - We introduce mixed LICORS, an algorithm for learning nonlinear, high-dimensional dynamics from spatio-temporal data, suitable for both prediction and simulation. Mixed LICORS extends the recent LICORS algorithm (Goerg and Shalizi, 2012) from hard clustering of predictive distributions to a non-parametric, EM-like soft clustering. This retains the asymptotic predictive optimality of LICORS, but, as we show in simulations, greatly improves out-of-sample forecasts with limited data. The new method is implemented in the publicly-available R package LICORS. PMID- 26279744 TI - Extracorporeal shock wave effectively attenuates brain infarct volume and improves neurological function in rat after acute ischemic stroke. AB - BACKGROUND: To investigate the effect of shock wave (SW) on brain-infarction volume (BIV) and neurological function in acute ischemic stroke (AIS) by left internal carotid artery occlusion in rats. METHODS AND RESULTS: SD rats (n=48) were divided into group 1 [sham-control (SC)], group 2 [SC-ECSW (energy dosage of 0.15 mJ/mm(2)/300 impulses)], group 3 (AIS), and group 4 (AIS-ECSW) and sacrificed by day 28 after IS induction. In normal rats, caspase-3, Bax and TNF alpha biomarkers did not differ between animals with and without ECSW therapy, whereas Hsp70 was activated post-ECSW treatment. By day 21 after AIS, Sensorimotor-functional test identified a higher frequency of turning movement to left in group 3 than that in group 4 (P<0.05). By day 28, brain MRI demonstrated lager BIV in group 3 than that in group 4 (P<0.001). Angiogenesis biomarkers at cellular (CD31, alpha-SMA+) and protein (eNOS) levels and number of neuN+ cells were higher in groups 1 and 2 than those in groups 3 and 4, and higher in group 4 than those in group 3, whereas VEGF and Hsp70 levels were progressively increased from groups 1 and 2 to group 4 (all P<0.001). Protein expressions of apoptosis (Bax, caspase 3, PARP), inflammation (MMP-9, TNF-alpha), oxidative stress (NOX-1, NOX-2, oxidized protein) and DNA-damage marker (gamma-H2AX), and expressions of gamma-H2AX+, GFAP+, AQP-4+ cells showed an opposite pattern compared to that of angiogenesis among the four groups (all P<0.001). CONCLUSION: ECSW therapy was safe and effective in reducing BIV and improved neurological function. PMID- 26279745 TI - Pancreatic and duodenal homeobox gene 1 (Pdx1) down-regulates hepatic transcription factor 1 alpha (HNF1alpha) expression during reprogramming of human hepatic cells into insulin-producing cells. AB - Ectopic expression of Pdx1 triggers rapid hepatocyte dedifferentiation by down regulating liver-enriched transcription factors and liver-specific functional genes such as hepatic nuclear factor-1alpha (HNF1alpha), albumin, and AAT. However, the links between Pdx1 over-expression and hepatic gene down-regulation are incompletely understood. HNF1alpha and HNF4alpha are important transcription factors that establish and maintain the hepatocyte phenotype. The human HNF4alpha gene contains two promoters (P1 and P2) that drive expression of P1-(HNF4alpha 1 6) or P2-(HNF4alpha 7-9)-derived isoforms, which are used in different tissues and at different times during development. We hypothesized that the relative expression of HNF1alpha and HNF4alpha following ectopic Pdx1 expression may promote hepatic cell dedifferentiation and transdifferentiation toward pancreatic beta-cells. We produced lentiviruses expressing Pdx1, Pdx1-VP16, and Ngn3, along with dual-color reporter genes to indicate hepatic and pancreatic beta-cell phenotype changes. Using these PTF alone or in combinations, we demonstrated that Pdx1 not only activates specific beta-cell genes but down-regulates HNF1alpha. Pdx1-mediated reduction of HNF1alpha is accompanied by altered expression of its major activator, HNF4alpha isoforms, down-regulating hepatic genes ALB and AAT. Pdx1 up-regulates HNF4alpha via the P2 promoter. These P2-driven isoforms compete with P1-driven isoforms to suppress target gene transcription. In Huh7 cells, the AF-1 activation domain is more important for transactivation, whereas in INS1 cells, the F inhibitory domain is more important. The loss and gain of functional activity strongly suggests that Pdx1 plays a central role in reprogramming hepatocytes into beta-cells by suppressing the hepatic phenotype. PMID- 26279746 TI - Phosphorylation of EZH2 at T416 by CDK2 contributes to the malignancy of triple negative breast cancers. AB - Triple-negative breast cancer (TNBC), which is closely related to basal-like breast cancer, is a highly aggressive subtype of breast cancer that initially responds to chemotherapy but eventually develops resistance. This presents a major clinical challenge as there are currently no effective targeted therapies available due to its lack of HER2 and estrogen receptor expression. Here, we show that cyclin E and the enhancer of zeste 2 (EZH2) are closely co-expressed in TNBC patients, and cyclin E/CDK2 phosphorylates EZH2 at T416 (pT416-EZH2) in vivo. Phosphorylation of EZH2 at T416 enhances the ability of EZH2 to promote TNBC cell migration/invasion, tumorsphere formation, and in vivo tumor growth. In addition, high pT416-EZH2 correlates with poorer survival in TNBC patients. These findings suggest that pT416 has the potential to serve as a therapeutic biomarker for the aggressive forms of breast cancer and provide a rationale for the use of CDK2 inhibitors to treat TNBC. PMID- 26279747 TI - Angiotensin II in atrial structural remodeling: the role of Ang II/JAK/STAT3 signaling pathway. AB - Ang II/JAK/STAT3 signaling pathway is known to be involved in atrial remodeling associated with development and progression of atrial fibrillation. In the present study, we used in vivo animal model and human atrial specimens to further characterize the role of this pathway in the atrial structural remodeling. We observed an elevated level of Ang II in the atrial samples of AF patients. This increase in Ang II was accompanied by increased expression of collagens I and III, MMP1, MMP2 and elevated phosphorylation of STAT3. Using rat models, we demonstrated that Ang II infusion induced profound changes in the level of apoptosis, expression of collagen subtypes I and III, caspase-3, caspase-8, MMP1, MMP2 and redistribution of cytochrome C. The data further support the key role of Ang II in the development of AF and highlight the specific mechanisms and changes associated with this process. PMID- 26279749 TI - Transplantation of bradykinin-preconditioned human endothelial progenitor cells improves cardiac function via enhanced Akt/eNOS phosphorylation and angiogenesis. AB - This study determines whether preconditioning (PC) of human endothelial progenitor cells (hEPCs) with bradykinin promotes infarcted myocardium repair via enhanced activation of B2 receptor (B2R)-dependent Akt/eNOS and increased angiogenesis. hEPCs with or without bradykinin preconditioning (BK-PC) were transplanted into a nude mouse model of acute myocardial infarction. Survival of transplanted cells was assessed using DiD-labeled hEPCs. Infarct size, cardiac function, and angiogenesis were measured 10 d after transplantation. Akt, eNOS, and vascular endothelial growth factor (VEGF) expressions in cardiac tissues were detected by western blotting, and NO production was determined using an NO assay kit. The cell migration and tube formation in cultured hEPCs were determined using transwell chamber and matrigel tube formation assays, respectively. The VEGF levels in the cell supernatant were measured using an enzyme-linked immunosorbent assay kit. BK-PC-hEPCs improved cardiac function, decreased infarct size, and promoted neovascularization 10 d following transplantation. PC increased Akt and eNOS phosphorylation, VEGF expression, and NO production in the ischemic myocardium. The effects of BK-PC were abrogated by HOE140 (B2R antagonist) and LY294002 (Akt antagonist). PC increased hEPC migration, tube formation, and VEGF levels in vitro. Activation of B2R-dependent Akt/eNOS phosphorylation by BK-PC promotes hEPC neovascularization and improves cardiac function following transplantation. PMID- 26279748 TI - Cisplatin induced sensory neuropathy is prevented by vascular endothelial growth factor-A. AB - Increased patient survival is a mark of modern anti-cancer therapy success. Unfortunately treatment side-effects such as neurotoxicity are a major long term concern. Sensory neuropathy is one of the common toxicities that can arise during platinum based chemotherapy. In many cases the current poor understanding of the neurological degeneration and lack of suitable analgesia has led to high incidences of patient drop out of treatment. VEGF-A is a prominent neuroprotective agent thus it was hypothesised to prevent cisplatin induced neuropathy. Systemic cisplatin treatment (lasting 3 weeks biweekly) resulted in mechanical allodynia and heat hyperalgesia in mice when compared to vehicle control. PGP9.5 sensory nerve fibre innervation was reduced in the plantar skin in the cisplatin treated group versus vehicle control mice. The cisplatin induced sensory neurodegeneration was associated with increased cleaved caspase 3 expression as well as a reduction in Activating Transcription Factor 3 and pan VEGF-A expression in sensory neurons. VEGF-A165b expression was unaltered between vehicle and cisplatin treatment. rhVEGF-A165a and rhVEGF-A165b both prevented cisplatin induced sensory neurodegeneration. Cisplatin exposure blunts the regenerative properties of sensory neurons thus leading to sensory neuropathy. However, here it is identified that administration of VEGF-A isoform subtypes induce regeneration and prevent cell death and are therefore a possible adjunct therapy for chemotherapy induced neuropathy. PMID- 26279750 TI - Intravenous administration of atorvastatin-pretreated mesenchymal stem cells improves cardiac performance after acute myocardial infarction: role of CXCR4. AB - BACKGROUND: The interaction between stromal cell-derived factor 1 (SDF-1) and its receptor CXC chemokine receptor 4 (CXCR4) plays an important role in mesenchymal stem cells (MSCs) migration and engraftment. Statins can increase the survival of MSCs. However, whether statins could enhance MSCs migration and engraftment is still unknown. Therefore, we designed the study to investigate whether atorvastatin (ATV) could enhance CXCR4 expression of MSCs and promote them homing toward the injured myocardium. METHODS AND RESULTS: Expression of CXCR4 was evaluated by flow cytometry and real time PCR. A transwell system was used to assess MSCs migration ability. Recruitment of systematically delivered MSCs to the infarcted heart was evaluated in Sprague-Dawley rats with acute myocardial infarction (AMI). ATV pretreatment enhanced the expression of CXCR4 and stimulated MSCs migration in vitro. However, the effect was largely abolished by CXCR4 neutralizing antibody. In AMI models, we found much more ATV-pretreated MSCs homing toward the infarcted myocardium than non-treated cells and this was accompanied by improved cardiac performance. CONCLUSIONS: ATV increases the migration ability of MSCs and improves cardiac performance due to up-regulated expression of CXCR4. These results suggest that ATV pretreatment of donor MSCs is an effective way to promote cell therapeutic potential for AMI. PMID- 26279751 TI - Effect of laminin-binding BDNF on induction of recurrent laryngeal nerve regeneration by miR-222 activation of mTOR signal pathway. AB - BACKGROUND AND AIM: Recurrent laryngeal nerve injury is a common severe complication in neck surgery, which can cause varying degrees of vocal fold paralysis and respiratory tract problems. In present study, the effects of laminin-binding brain derived neurotrophic factor (LBD-BDNF) on recurrent laryngeal nerve regeneration were explored and its possible mechanism was investigated. METHODS: LBD-BDNF or NAT-BDNF (BDNF without LBD binding) treatment was performed in laryngeal nerve injured rabbits for sixteen weeks. The laryngeal nerve was removed, and histological examination as well as laryngeal electromyography was employed to evaluate its morphology and function of conduction. PC12 cells were cultured to investigate the mechanisms underlying the effects of LBD-BDNF. Neurite outgrowth, proliferation and migration were determined in nerve cells. The expression of miRNAs and protein of mTOR was quantified by real-time PCR and western blotting respectively. RESULTS: In vivo experiments, LBD-BDNF significantly improved the histological structure and function of recurrent laryngeal nerve compared with NAT-BDNF. LBD-BDNF also markedly promoted neurite outgrowth, proliferation and migration in PC12 cells in vitro experiments. The levels of miR-222 and p-mTOR were up-regulated by LBD-BDNF treatment in both in vivo and in vitro experiments. miR-222 inhibitor attenuated the expression of phosphorylated mTOR and miR-222 mimic enhanced its expression in PC12 cells. In addition, the improved nerve conduction by LBD-BDNF was canceled by miR-222 inhibitor, and the mTOR inhibitor reversed the effects of miR 222 inhibitor on LBD-BDNF treated cells. CONCLUSIONS: The present study revealed that LBD-BDNF promoted the recurrent laryngeal nerve regeneration in laryngeal nerve injured rabbits. The underlying mechanism was closely related to activation of p-mTOR by miR-222. PMID- 26279752 TI - Antimicrobial peptide LL-37 along with peptidoglycan drive monocyte polarization toward CD14(high)CD16(+) subset and may play a crucial role in the pathogenesis of psoriasis guttata. AB - The human cathelicidin LL-37 peptide is overexpressed in psoriasis and has been demonstrated to be a multifunctional modulator of innate immune response elements, including monocytes. Monocytes, categorized into three populations based on the cell surface expression of CD14 and CD16, are activated in psoriasis guttate and are commonly triggered by streptococcal infections. Peptidoglycan (PGN) is a major cell-wall component of streptococcus, and an increasing number of PGN-containing cells have been detected in psoriasis. Since there are independent reports of both PGN and LL-37 influencing monocytes, we tried to evaluate the effect of human LL-37 on PGN-induced monocyte activity and differentiation and subsequently studied their correlation with the pathogenesis of psoriasis guttate. The results revealed that monocytes from the peripheral blood of healthy individuals resulted in their polarization toward the CD14(high)CD16(+) subset, when cultured with PGN in the presence of the LL-37 peptide. This peptide further induced PGN-driven differentiated monocytes into immature dendritic cells (iDC), as evident by the increased expression of CD1a, CD86, and HLA-DR markers, resulting in the induction of T cell proliferation and Th17 polarization. Furthermore, our data suggested that psoriasis guttata patients have significantly higher percentages of CD14(high)CD16(+) monocytes as well as circulating levels of LL-37, soluble form of triggering receptor expressed on myeloid cells (sTREM-1) levels, and anti-streptolysin O (ASO) levels, as compared to healthy controls. Psoriasis guttata patients also showed a positive correlation between the percentage of CD14(high)CD16(+) monocytes and the serum levels of sTREM-1 as well as the Psoriasis Area and Severity Index (PASI) scores. Therefore, we concluded that LL-37 in synergy with PGN directs monocyte polarization and differentiation into a proinflammatory phenotype, which might play a crucial role in the pathogenesis of psoriasis. PMID- 26279753 TI - LTPB2 acts as a prognostic factor and promotes progression of cervical adenocarcinoma. AB - Latent transforming growth factor-beta-1 binding protein-2 (LTBP-2) is a member of the fibrillin/LTBP super family of extracellular matrix proteins, found to be overexpressed in certain malignant tumors. However, the clinical significance and biological role of LTBP-2 in cervical adenocarcinoma has remains unclear. We found that the expression of LTBP2 was higher in cervical adenocarcinoma than in normal cervical epithelial tissue as assessed by immunohistochemistry. Expression of LTBP2 is related to clinical stage, cervical tumor size, depth of cervical stromal invasion and lymph node metastasis. Knockdown of LTBP2 expression can inhibit the proliferation and migration of HeLa cells. Moreover, LTBP2 knockdown affected multiple tumor-related pathway genes including: the MAPK signaling pathway, the PI3K-AKT signaling pathway, receptor tyrosine kinase signaling and the P53 pathway. Taken together, this work suggests that LTBP2 may promote the development of cervical adenocarcinoma and serve as a prognostic factor in the clinical evaluation of patients with cervical adenocarcinoma. Our findings provide a new strategy for the diagnosis and treatment of cervical adenocarcinoma. PMID- 26279754 TI - Angiogenesis effect of therapeutic ultrasound on HUVECs through activation of the PI3K-Akt-eNOS signal pathway. AB - Therapeutic angiogenic effects of low-intensity ultrasound have been reported in endothelial cells and animal models of hind limb ischemia. It has been shown that the proliferation, migration, and tube formation of endothelial cells play critical roles in angiogenesis. The purpose of this study was to determine the underlying mechanism of low-intensity continuous therapeutic ultrasound on angiogenesis in endothelial cells. In the present study, human umbilical vein endothelial cells (HUVECs) were simulated of low-intensity therapeutic ultrasound (TUS, 1 MHz, 0.3 W/cm(2), 9 minute per day) for 3 days, and we observed migration, tube formation, and expression of endothelial nitric oxide synthase (eNOS) and serine/threonine kinase (Akt) in HUVECs. Specific inhibitors of eNOS and phosphoinositide 3-kinase (PI3K) were added to the culture medium and TUS induced changes in the pathways that mediate angiogenesis were investigated. After exposure to TUS, HUVECs tube formation and migration were significantly promoted, which was blocked by the eNOS inhibitor Immunofluorescence assay and Western blotting analysis demonstrated that eNOS expression in the HUVECs was significantly increased after TUS exhibition. Proteins of phosphorylated eNOS and Akt were both up-regulated after TUS stimulation. However, the specific inhibitor of PI3K not only significantly decreased the expression of p-Akt, but also down regulated the p-eNOS. This suggested that the PI3K/Akt signal pathway might participate in modulating the activity of eNOS. In short, TUS therapy promotes angiogenesis through activation of the PI3K-Akt-eNOS signal cascade in HUVECs. PMID- 26279755 TI - Different localization and expression of protein kinase C-beta in kidney cortex of diabetic nephropathy mice and its role in telmisartan treatment. AB - AIM: This study aims to investigate the localization and expression of protein kinase C-beta I and beta II in kidney cortex of diabetic nephropathy mice and their roles in telmisartan treatment. METHODS: 18 mice were randomly divided into three groups: normal group, diabetic nephropathy group and telmisartan-treated group. The localization and expression of protein kinase C-beta I and beta II were measured with confocal immunofluorescence laser scanning microscopy, immunohistochemistry and western blotting. The expression of transforming growth factor-beta 1 and vascular endothelial growth factor in glomeruli was detected by immunohistochemistry. RESULTS: Compared to the normal mice, the expression and localization of protein kinase C-beta I and beta II are differed in diabetic nephropathy mice, with increased expression of protein kinase C-beta I but decreased level of protein kinase C-beta II. Meanwhile, the expression of transforming growth factor-beta 1 and vascular endothelial growth factor showed increase in the glomeruli of diabetic nephropathy, compared to the controls. Also, protein kinase C-beta I exhibited a positive correlation to transforming growth factor-beta 1 (r = 0.649, P = 0.030), but no correlation to vascular endothelial growth factor (r = 0.387, P = 0.079). Telmisartan treatment exercised significant beneficial role in diabetic nephropathy, which is associated with protein kinase C-beta I, but not beta II. CONCLUSIONS: The expression and localization of protein kinase C-beta I and beta II differ in the diabetic nephropathy, and such difference is associated with the pathogeneses of diabetic nephropathy. PMID- 26279756 TI - Clinical significance of coexpression of L-type amino acid transporter 1 (LAT1) and ASC amino acid transporter 2 (ASCT2) in lung adenocarcinoma. AB - BACKGROUND: L-type amino acid transporter 1 (LAT1) and ASC amino acid transporter 2 (ASCT2) have been associated with tumor growth and progression. However, the clinical significance of LAT1 and ASCT2 coexpression in the prognosis of patients with lung adenocarcinoma remains unclear. METHODS: In total, 222 patients with surgically resected lung adenocarcinoma were investigated retrospectively. Tumor sections were stained immunohistochemically for LAT1, ASCT2, CD98, phosphorylated mammalian target-of-rapamycin (p-mTOR), and Ki-67, and microvessel density (MVD) was determined by staining for CD34. Epidermal growth factor receptor (EGFR) mutation status was also examined. RESULTS: LAT1 and ASCT2 were positively expressed in 22% and 40% of cases, respectively. Coexpression of LAT1 and ASCT2 was observed in 12% of cases and was associated significantly with disease stage, lymphatic permeation, vascular invasion, CD98, Ki-67, and p-mTOR. Only LAT1 and ASCT2 coexpression indicated a poor prognosis for lung adenocarcinoma. Furthermore, this characteristic was recognized in early-stage patients, especially those who had wild-type, rather than mutated, EGFR. Multivariate analysis confirmed that the coexpression of LAT1 and ASCT2 was an independent factor for predicting poor outcome. CONCLUSIONS: LAT1 and ASCT2 coexpression is an independent prognostic factor for patients with lung adenocarcinoma, especially during the early stages, expressing wild-type EGFR. PMID- 26279757 TI - DLAT subunit of the pyruvate dehydrogenase complex is upregulated in gastric cancer-implications in cancer therapy. AB - An iTRAQ-based tandem mass spectrometry approach was employed to relatively quantify proteins in the membrane proteome of eleven gastric cancer cell lines relative to a denominator non-cancer gastric epithelial cell line HFE145. Of the 882 proteins detected, 57 proteins were found to be upregulated with > 1.3-fold change in at least 6 of the 11 cell lines. Bioinformatics analysis revealed that these proteins are significantly associated with cancer, cell growth and proliferation, death, survival and cell movement. The catalogue of membrane proteins presented that are potential regulators/effectors of gastric cancer progression has implications in cancer therapy. DLAT, a subunit of the pyruvate dehydrogenase complex, was selected as a candidate protein for further studies as its function in gastric cancer has yet to be established. SiRNA studies supported a role of DLAT in gastric cancer cell proliferation and carbohydrate metabolism, reprogramming of which is a hallmark of cancer. Our study contributes to recent interest and discussion in cancer energetics and related phenomena such as the Warburg and Reverse Warburg effects. Future mechanistic studies should lead to the elucidation of the mode of action of DLAT in human gastric cancer and establish DLAT as a viable drug target. PMID- 26279758 TI - Epigenetic regulation of traf2- and Nck-interacting kinase (TNIK) in polycystic ovary syndrome. AB - Emerging evidence has led to considerable interest in the role of Traf2- and Nck interacting kinase (TNIK) in polycystic ovary syndrome (PCOS) development. However, the epigenetic mechanism regulating TNIK transcription remains largely unknown. Here, we show that (i) TNIK mRNA expression is significantly increased in PCOS ovarian tissues, compared to normal ovarian tissues; (ii) PCOS ovarian tissues exhibit a hypermethylation pattern at the cg10180092 site, (iii) and cg10180092 is the critical site for the transcriptional regulation of TNIK. Mechanistically, hypermethylated cg10180092 site-mediated loss of holocarboxylase synthetase (HLCS)-related H3K9me enrichment activated TNIK transcription in PCOS ovarian tissues. Notably, a substantial body of evidence indicates that DNA hypermethylation is an alternative mechanism for gene inactivation, and a new role for DNA hypermethylationmediated TNIK activating was observed in this study. This may improve our understanding of divergent transcriptional regulation in the initiation and progression of TNIK-related PCOS. PMID- 26279759 TI - Prognostic significance of L-type amino acid transporter 1 (LAT1) expression in patients with ovarian tumors. AB - AIM: Amino acid transporters are essential for the growth, progression and the pathogenesis of various cancers. However, it remains obscure about the clinicopathological significance of L-type amino acid transporter 1 (LAT1) and system ASC amino acid transporter 2 (ASCT2) for patients with human ovarian tumors. The aim of this study is to elucidate the prognostic role of these amino acid transporters in ovarian tumor. METHODS: One-hundred forty-two patients with surgically resected ovarian tumors were analyzed by immunohistochemistry. Expression of LAT1, ASCT2, CD98, Ki-67 and microvessel density (MVD) determined by CD34 were evaluated using specimens of the resected tumors. RESULTS: LAT1 and ASCT2 were positively expressed in 39% and 53%, respectively, of ovarian tumors (n=142) and 50% and 57%, respectively, of epidermal ovarian cancers (n=107). A positive LAT1 expression was closely correlated with the expression for ASCT2 and CD98, and cell proliferation (Ki-67) in ovarian cancer. By multivariate analysis, LAT1 was clarified as a significant independent marker for predicting a poor overall survival (OS). The expression of LAT1 could clearly discriminate between epidermal ovarian cancer and borderline malignancy. The expression level of LAT1 within ovarian cancer cells varied among serous adenocarcinoma, endometrioid adenocarcinoma, clear cell adenocarcinoma and mucinous adenocarcinoma and we found LAT1 expression was higher in clear cell adenocarcinoma than other histological types. CONCLUSIONS: LAT1 is highly expressed in various ovarian tumors and a positive LAT1 expression can serve as a significant independent factor for predicting a poor OS in patients with epidermal ovarian cancer. PMID- 26279760 TI - VSIG4 is highly expressed and correlated with poor prognosis of high-grade glioma patients. AB - The high-grade glioma (HGG) remains as the greatest challenge for cancer management worldwide. Identification of novel therapeutics and diagnostic method is in urgent need. The V-set and immunoglobulin domain-containing protein 4 (VSIG4) is a complement receptor for C3b/iC3b and inhibits cytotoxic T lymphocytes activation, which may play important roles in glioma oncogenesis. In this study, we performed immunohistochemistry in tissue microarray to determine the expression of VSIG4 in malignant glioma and normal brain. We then applied univariate and multivariate analyses to evaluate the expression of VSIG4 and correlated with prognosis of glioma patients. We have shown that VSIG4 was significantly elevated in high-grade glioma compared with those of normal brain tissues (P<0.001). We have also found that high VSIG4 expression was an independent prognostic factor for a shorter progression-free survival (PFS) and overall survival (OS) in high-grade glioma patients [hazard ratio (HR) =1.786, P=0.011 and HR=2.199, P=0.001, respectively]. Patients with low VSIG4 expression had a significantly longer median OS and PFS than those with high VSIG4 expression. Subgroup analysis stratifying HGG patients by both VSIG4 expression and tumor grade further confirmed the independent prognostic role of VSIG4 in HGG patients, while no adjuvant radiotherapy, small extent of resection and higher tumor grade were other three independent risk factors for HGG poor prognosis. Similar findings were also obtained using data from Cancer Genome Atlas (TCGA). Together, our results support that VISG4 can be used as a prognostic factor and potentially an immunotherapeutic target for glioma. PMID- 26279762 TI - Is There a Role for Spin Doctors in Med Ed Research? PMID- 26279761 TI - CD39 is a promising therapeutic antibody target for the treatment of soft tissue sarcoma. AB - Soft tissue sarcoma (STS) is a heterogenous tumor arising from the embryonic mesoderm represented by approximately 50 histological subtypes. Effective therapeutic intervention is lacking for recurrent, late stage and metastatic disease. CD39, a cell-surface ectonucleotidase, has previously been shown to be upregulated in hematological malignancies and various epithelial tumors, but not in STS. Here, we show by mass spectrometry and immunohistochemistry that CD39 is highly expressed in primary patient sarcoma samples. Moreover, CD39 nucleotidase activity is enhanced in fibrosarcoma compared with normal control cells. We demonstrate that an inhibitory monoclonal anti-CD39 antibody, abrogates CD39 enzymatic activity significantly and prolongs survival in a lethal metastatic patient-derived sarcoma model. Taken together, the data suggest CD39 is a novel therapeutic target for the treatment of STS. PMID- 26279763 TI - Gamification: Implications for Curricular Design. PMID- 26279764 TI - From the Desk of the Program Director: Show Me the Rankings! PMID- 26279765 TI - Instinctive Clinical Teaching: Erasing the Mental Boundary Between Clinical Education and Patient Care to Promote Natural Learning. AB - Effective clinical teaching is essential in physician education, yet faculty members rarely receive formal training in clinical teaching. Formal models for training clinical educators are often tedious and require significant time and effort. Instinctive clinical teaching allows clinicians to seamlessly integrate and promote effective teaching into their clinical practice. The approach is guided by similarities between the components of Kolb's experiential learning cycle-concrete experience, reflective observation, abstract conceptualization, and active experimentation-and the elements of the patient care process-history and physical, initial assessment, differential, hypothesis, final diagnosis, management, and follow-up. Externalization of these clinical thought processes allows for inclusion of learners and promotes effective clinical teaching. PMID- 26279766 TI - Impact of the Affordable Care Act on Grant-Supported Primary Care Faculty Development. AB - Health reform requires well-trained primary care physicians with new skills. Teaching faculty need to develop proficiency to deliver care in new models and systems, to lead change, and to teach these skills to the next generation of clinicians. Title VII Section 747 of the Public Health Service Act, modified and reauthorized under the Patient Protection and Affordable Care Act (ACA), is the only federal program that specifically supports the professional development of primary care faculty. We analyzed the effect of the modifications under the ACA on a funding opportunity announcement addressing faculty development needs and attributes of funded applications, including geographic regions. The data offer useful insights to programs interested in tapping sources of support for primary care faculty development. The data also show that targeted federal funding can bring about changes that contribute to an up-to-date, responsive primary care workforce. Title VII programs, as amended by the ACA, focus on curriculum development, teaching in community-based settings, and integrating patient centered medical home concepts and interprofessional education and practice into the training of the next generation of physicians. These strategies drive change and improve the quality of care and patient outcomes. PMID- 26279767 TI - Expertise, Time, Money, Mentoring, and Reward: Systemic Barriers That Limit Education Researcher Productivity-Proceedings From the AAMC GEA Workshop. AB - BACKGROUND: To further evolve in an evidence-based fashion, medical education needs to develop and evaluate new practices for teaching, learning, and assessment. However, educators face barriers in designing, conducting, and publishing education research. OBJECTIVE: To explore the barriers medical educators face in formulating, conducting, and publishing high-quality medical education research, and to identify strategies for overcoming them. METHODS: A consensus workshop was held November 5, 2013, at the Association of American Medical Colleges annual meeting. A working group of education research experts and educators completed a preconference literature review focusing on barriers to education research. During the workshop, consensus-based and small group techniques were used to refine the broad themes into content categories. Attendees then ranked the most important barriers and strategies for overcoming them with the highest potential impact. RESULTS: Barriers participants faced in conducting quality education research included lack of (1) expertise, (2) time, (3) funding, (4) mentorship, and (5) reward. The strategy considered most effective in overcoming these barriers involved building communities of education researchers for collaboration and networking, and advocating for education researchers' interests. Other suggestions included trying to secure increased funding opportunities, developing mentoring programs, and encouraging mechanisms to ensure protected time. CONCLUSIONS: Barriers to education research productivity clearly exist. Many appear to result from feelings of isolation that may be overcome with systemic efforts to develop and enable communities of practice across institutions. Finally, the theme of "reward" is novel and complex and may have implications for education research productivity. PMID- 26279768 TI - Impact of Global Health Experiences During Residency on Graduate Practice Location: A Multisite Cohort Study. AB - BACKGROUND: The impact of global health experiences on practice location is not clear. OBJECTIVE: We studied whether participants in global health tracks (GHTs) and global health electives (GHEs) were more likely to practice in underserved areas. METHODS: Our study used the 2010 American Medical Association Masterfile to evaluate the practice location of 999 graduates (1980-2009) from 5 family medicine programs. The variable of interest was participation in a GHT or GHE. Outcome measures were percentage of graduates practicing in (1) health professional shortage areas, (2) medically underserved areas or populations, (3) rural areas, (4) areas of dense poverty, and (5) any rural or underserved area. We also examined whether availability of a GHT or GHE in the program affected nonparticipants' practice location. RESULTS: Sixty-four percent (112 of 174) of participants practiced in areas of dense poverty compared with 56% (463 of 825) of nonparticipants (P = .04). Those graduating after GHT implementation were more likely to practice in a rural or underserved area compared with those graduating before implementation. After controlling for potential confounders, GHT participants were not more likely to work in an underserved area. CONCLUSIONS: Graduates of programs with global health experiences were more likely to practice in an underserved or rural area. Making these experiences available may affect participants and nonparticipants. PMID- 26279769 TI - Recognizing and Alleviating Moral Distress Among Obstetrics and Gynecology Residents. AB - BACKGROUND: Obstetrics and gynecology residents face difficult clinical situations and decisions that challenge their moral concepts. OBJECTIVE: We examined how moral and nonmoral judgments about patients are formulated, confirmed, or modified and how moral distress may be alleviated among obstetrics gynecology residents. METHODS: Three focus groups, guided by open-ended interview questions, were conducted with 31 obstetrics-gynecology residents from 3 academic medical institutions in northeast Ohio. Each focus group contained 7 to 14 participants and was recorded. Two investigators independently coded and thematically analyzed the transcribed data. RESULTS: Our participants struggled with 3 types of patients perceived as difficult: (1) patients with chronic pain, including patients who abuse narcotics; (2) demanding and entitled patients; and (3) irresponsible patients. Difficult clinical encounters with such patients contribute to unalleviated moral distress for residents and negative, and often inaccurate, judgment made about patients. The residents reported that they were able to prevent stigmatizing judgments about patients by keeping an open mind or recognizing the particular needs of patients, but they still felt unresolved moral distress. CONCLUSIONS: Moral distress that is not addressed in residency education may contribute to career dissatisfaction and ineffective patient care. We recommend education and research on pedagogical approaches in residency education in a model that emphasizes ethics and professional identity development as well as the recognition and alleviation of moral distress. PMID- 26279770 TI - Using Simulation Education With Deliberate Practice to Teach Leadership and Resource Management Skills to Senior Resident Code Leaders. AB - BACKGROUND: Cardiopulmonary arrests are rare, high-stakes events that benefit from using crisis resource management (CRM). Simulation-based education with deliberate practice can promote skill acquisition. OBJECTIVE: We assessed whether using simulation-based education to teach CRM would lead to improved performance, compared to a lecture format. METHODS: We tested third-year internal medicine residents in simulated code scenarios. Participants were randomly assigned to simulation-based education with deliberate practice (SIM) group or lecture (LEC) group. We created a checklist of CRM critical actions (which includes announcing the diagnosis, asking for help/suggestions, and assigning tasks), and reviewed videotaped performances, using a checklist of skills and communications patterns to identify CRM skills and communication efforts. Subjects were tested in simulated code scenarios 6 months after the initial assessment. RESULTS: At baseline, all 52 subjects recognized distress, and 92% (48 of 52) called for help. Seventy-eight percent (41 of 52) did not succeed in resuscitating the simulated patient or demonstrate the CRM skills. After intervention, both groups (n = 26 per group) improved. All SIM subjects announced the diagnosis compared to 65% LEC subjects (17 of 26, P = .01); 77% (20 of 26) SIM and 19% (5 of 26) LEC subjects asked for suggestions (P < .001); and 100% (26 of 26) SIM and 27% (7 of 26) LEC subjects assigned tasks (P < .001). CONCLUSIONS: The SIM intervention resulted in significantly improved team communication and cardiopulmonary arrest management. During debriefing, participants acknowledged the benefit of the SIM sessions. PMID- 26279771 TI - Determinants of Patient Satisfaction in Internal Medicine Resident Continuity Clinics: Findings of the Educational Innovations Project Ambulatory Collaborative. AB - BACKGROUND: Many internal medicine programs have reorganized their resident continuity clinics to improve the ambulatory care experience for residents. The effect of this redesign on patient satisfaction is largely unknown. METHODS: Our multi-institutional, cross-sectional study included 569 internal medicine residents from 11 programs participating in the Educational Innovations Project Ambulatory Collaborative. An 11-item patient satisfaction survey from the Consumer Assessment of Healthcare Providers and Systems was used to assess patient satisfaction, comparing patient satisfaction in traditional models of weekly continuity clinic with 2 new clinic models. We then examined the relationship between patient satisfaction and other practice variables. RESULTS: Patient satisfaction responses related to resident listening and communication skills, knowledge of medical history, perception of adequate visit time, overall rating, and willingness to refer to family and friends were significantly better in the traditional and block continuity models than the combination model. Higher ambulatory workload was associated with reduced patient perception of respect shown by the physician. The percentage of diabetic patients with glycated hemoglobin < 8% was positively correlated with number of visits, knowledge of medical history, perception of respect, and higher scores for recommending the physician to others. The percentage of diabetic patients with low density lipoprotein < 100 mg/dL was positively correlated with the physician showing respect. CONCLUSIONS: Patient satisfaction was similar in programs using block design and traditional models for continuity clinic, and both outperformed the combination model programs. There was a delicate balance between workload and patient perception of the physician showing respect. Care outcome measures for diabetic patients were associated with aspects of patient satisfaction. PMID- 26279772 TI - Relationship Between Postinterview Correspondence From Residency Program Applicants and Subsequent Applicant Match Outcomes. AB - BACKGROUND: Studies show postinterview communication from applicants may affect their placement on the program's National Resident Matching Program (NRMP) rank order list. OBJECTIVE: To determine whether postinterview correspondence from applicants to a residency program is associated with the applicant's subsequent position on the program's rank list. METHODS: During 2 recruitment seasons, we collected postinterview correspondence from applicants to 1 residency program. Applicant characteristics and the content and timing of correspondence were compared with the applicant's position on the program's rank list. Data were analyzed using the Pearson chi(2) test. RESULTS: Of 470 applicants interviewed, 290 (61.7%) sent unsolicited correspondence to the program after interviewing. Ten percent (29 of 290) stated they planned to rank the program first, 11.7% (34 of 290) that they planned to rank it highly, and 78.3% (227 of 290) gave no indication of ranking intentions. Applicants who corresponded were no more likely to be ranked in the top 2 quartiles on the rank list than those who did not (P = .32) nor were applicants who communicated plans to rank the program "first" or "highly" ranked higher than other corresponding applicants (P = .34). Of the 16 applicants who planned to rank the program "first" and who were ranked in the program's match range, 5 did not match with the program, suggesting they may have misled the program. CONCLUSIONS: Postinterview correspondence by applicants was not associated with position on the rank order list. Correspondence does not benefit the applicant and can lead to misleading statements, which may violate the NRMP participation agreement. PMID- 26279773 TI - Brand Name Statin Prescribing in a Resident Ambulatory Practice: Implications for Teaching Cost-Conscious Medicine. AB - BACKGROUND: Several national initiatives aim to teach high-value care to residents. While there is a growing body of literature on cost impact of physicians' therapeutic decisions, few studies have assessed factors that influence residents' prescribing practices. OBJECTIVE: We studied factors associated with intensive health care utilization among internal medicine residents, using brand name statin prescribing as a proxy for higher-cost care. METHODS: We conducted a retrospective, cross-sectional analysis of statin prescriptions by residents at an urban academic internal medicine program, using electronic health record data between July 1, 2010, and June 30, 2011. RESULTS: For 319 encounters by 90 residents, patients were given a brand name statin in 50% of cases. When categorized into quintiles, the bottom quintile of residents prescribed brand name statins in 2% of encounters, while the top quintile prescribed brand name statins in 98% of encounters. After adjusting for potential confounders, including patient characteristics and supervising attending, being in the primary care track was associated with lower odds (odds ratio [OR], 0.38; P = .02; 95% confidence interval [CI], 0.16-0.86), and graduating from a medical school with an above-average hospital care intensity index was associated with higher odds of prescribing brand name statins (OR, 1.70; P = .049; 95% CI, 1.003-2.88). CONCLUSIONS: We found considerable variation in brand name statin prescribing by residents. Medical school attended and residency program type were associated with resident prescribing behavior. Future interventions should raise awareness of these patterns in an effort to teach high-value, cost-conscious care to all residents. PMID- 26279774 TI - Construct Validity and Generalizability of Simulation-Based Objective Structured Clinical Examination Scenarios. AB - BACKGROUND: It is not known if construct-related validity (progression of scores with different levels of training) and generalizability of Objective Structured Clinical Examination (OSCE) scenarios previously used with non-US graduating anesthesiology residents translate to a US training program. OBJECTIVE: We assessed for progression of scores with training for a validated high-stakes simulation-based anesthesiology examination. METHODS: Fifty US anesthesiology residents in postgraduate years (PGYs) 2 to 4 were evaluated in operating room, trauma, and resuscitation scenarios developed for and used in a high-stakes Israeli Anesthesiology Board examination, requiring a score of 70% on the checklist for passing (including all critical items). RESULTS: The OSCE error rate was lower for PGY-4 than PGY-2 residents in each field, and for most scenarios within each field. The critical item error rate was significantly lower for PGY-4 than PGY-3 residents in operating room scenarios, and for PGY-4 than PGY-2 residents in resuscitation scenarios. The final pass rate was significantly higher for PGY-3 and PGY-4 than PGY-2 residents in operating room scenarios, and also was significantly higher for PGY-4 than PGY-2 residents overall. PGY-4 residents had a better error rate, total scenarios score, general evaluation score, critical items error rate, and final pass rate than PGY-2 residents. CONCLUSIONS: The comparable error rates, performance grades, and pass rates for US PGY-4 and non-US (Israeli) graduating (PGY-4 equivalent) residents, and the progression of scores among US residents with training level, demonstrate the construct-related validity and generalizability of these high-stakes OSCE scenarios. PMID- 26279775 TI - Assessing Family Medicine Residents' Communication Skills From the Patient's Perspective: Evaluating the Communication Assessment Tool. AB - BACKGROUND: The Communication Assessment Tool (CAT), a paper-based patient survey, is 1 method to assess residents' interpersonal and communication skills. To further enhance the interpretation of the CAT, benchmark data are needed. OBJECTIVE: We sought to expand upon initial benchmarking data for the use of the CAT as an evaluation tool in family medicine residency programs. METHODS: Data were collected on 120 residents from 7 family medicine residency programs. Following an appointment with a resident, 1703 patients completed the CAT. RESULTS: The overall mean percentage of items rated as excellent was 73%. Significant differences were found in the overall percentage of items rated as "excellent" based on location of training (78% US graduate versus 71% international medical graduate) and native language of the resident (76% English speaking versus 69% non-English speaking). There were no significant differences found in the overall percentage of items rated as excellent based on the year of training or sex of the residents. CONCLUSIONS: These benchmarking data allow family medicine residency programs to compare the performance of their residents with other programs. The CAT can be used as an evaluation and a learning tool in family medicine and may be applicable to other specialties. PMID- 26279776 TI - Use of the Electronic Health Record to Track Continuity of Care in Neurological Surgery Residency. AB - BACKGROUND: Continuity of care in neurological surgery includes preoperative planning, technical and cognitive operative experience, and postoperative follow up. Determining the extent of continuity of care with duty hour limits is problematic. OBJECTIVE: We used electronic health record data to track continuity of care in a neurological surgery program and to assess changes in rotation requirements. METHODS: The electronic health record was surveyed for all dictated resident-neurological surgery patient encounters (excluding progress notes), discharge summaries, and bedside procedures (July 2009-November 2011). Encounters were designated as preoperative, operative, or postoperative and were grouped by postgraduate year (PGY)-1 through PGY-6. RESULTS: A total of 6382 dictations were reviewed, with 5231 (82.0%) pertinent to neurological surgery. Of the 1469 operative notes, 303 (20.6%) had a record of an encounter with the operating resident in either a postoperative or preoperative setting. Preoperative encounters totaled 10.1% (148 of 1469); postoperative, 5.1% (75 of 1469); and encounters with both were 5.4% (80 of 1469). Continuity of care was as follows: PGY-1, 13.8% (4 of 29); PGY-2, 17.4% (26 of 149); PGY-3, 29.0% (36 of 124); PGY 4, 24.8% (73 of 294); PGY-5, 28.8% (109 of 379); and PGY-6, 11.1% (55 of 494). One of the highest continuity rates was observed in a rotation specifically constructed to enhance continuity of care. CONCLUSIONS: The electronic health record can be used to track resident continuity of care in neurological surgery. The primary operating resident saw the patient in nonoperative settings, such as general admission, clinic visitation, or consultation in 20.6% (303 of 1469) of cases. PMID- 26279777 TI - Continuity of Care in the Training Environment: Anesthesiology Residency in the Ambulatory Surgery Setting. AB - BACKGROUND: Anesthesiology residents acquire clinical skills and acumen primarily from experience providing anesthesia for procedural cases, with prior preparation maximizing learning. Ambulatory surgery and associated management styles create fluid anesthesiology staffing-reducing predictability for learners and disrupting continuity of care. OBJECTIVE: This prospective, observational study aimed to quantify anesthesia personnel changes in the operating rooms of a single teaching hospital. METHODS: For a 5-week period, Monday through Friday, we recorded the surgical schedule on the prior evening. After the day of surgery, tracking software provided a list of cases performed. We completed electronic health record review for each case, recorded the actual anesthesiology personnel involved, and compared that to the personnel originally scheduled. We also recorded the occurrence of any permanent transitions of care within a case, the type of operation, and the anesthesia start and end times. RESULTS: Anesthesia providers included 47 residents and 32 attending physicians. The study period included 1285 scheduled cases, 55% (n = 711) of which were started and finished by the originally scheduled resident and attending physician. Including canceled cases (126 of 1285, 10%) and added cases (207 of 1366, 15%), residents started anesthetics on patients and with attending physicians assigned to them from the day before 54% of the time. Transitions of care occurred in 19% (260 of 1366) of the cases. CONCLUSIONS: Anesthesiology residents prepare for many procedures that do not eventuate and frequently start other cases without prior opportunity for preparation and study. Transitions of care further reduce continuity of care and fragment supervision. PMID- 26279778 TI - International Residency Program Evaluation: Assessing the Reliability and Initial Validity of the ACGME-I Resident Survey in Abu Dhabi, United Arab Emirates. AB - BACKGROUND: Educators agree on the importance of assessing the quality of graduate medical education. In the United States, the Accreditation Council for Graduate Medical Education (ACGME) resident survey is an important part of the accreditation process, yet some studies have questioned its validity. OBJECTIVE: We assessed the reliability and acceptance of the ACGME-International (ACGME-I) resident survey in the culturally distinct, nonnative English-speaking resident population of Abu Dhabi in the United Arab Emirates. METHODS: A total of 158 residents in ACGME-I accredited institutions in Abu Dhabi received an online link to the ACGME-I survey. Reliability analysis was conducted using the Cronbach alpha. A focus group was then held with a convenience sample of 25 residents from different institutions and specialties to understand potential challenges encountered by survey participants. RESULTS: Completed surveys were received from 116 residents (73.4%). The 39 items in the survey demonstrated high reliability, with a Cronbach alpha of 0.918. Of the 5 subscales, 4 demonstrated acceptable to very good reliability, ranging from 0.72 to 0.888. The subscale "resources" had lower reliability at 0.584. Removal of a single item increased the Cronbach alpha to a near-acceptable score of 0.670. Focus group results indicated that the survey met standards for readability, length, and time for completion. CONCLUSIONS: The ACGME-I resident survey demonstrates acceptable reliability and validity for measuring the perceptions of residents in an international residency program. The data derived from the survey can offer an important set of metrics for educational quality improvement in the United Arab Emirates. PMID- 26279779 TI - Assessing Effectiveness of a Geriatrics Rotation for Second-Year Internal Medicine Residents. AB - BACKGROUND: Residents need to acquire an understanding of the biopsychosocial aspects of caring for older adults with chronic illness, along with effective use of interdisciplinary services inside and outside of the hospital. OBJECTIVE: We expanded the geriatric medicine experience for second-year internal medicine residents and present the results of the first year's experience. METHODS: We paired a mandatory rotation for postgraduate year-2 internal medicine residents (2 weeks of day and 1 week of night inpatient experience in the Acute Care for Elders Unit), and a 1-week outpatient systems-based practice experience with online modules and readings. Evaluation included a case presentation, an oral examination, a written questionnaire for all residents, and a global assessment of the residents' performance on the geriatrics portion of the 2012 In-Training Examination (ITE). RESULTS: All residents passed their oral examination; there was little difference between classes in systems-based practice knowledge. More than 90% (21 of 23) of the residents who took the rotation reported that it left a lasting impression on how they would care for their patients. Mean ITE scores in geriatrics for all residents increased from 53% (versus 61% overall) in 2010 to 87% (versus 81%) in 2012, although they dropped to 69% (versus 82%) in 2013. CONCLUSIONS: A rotation in geriatrics that is highly rated and covers both acute care and systems-based practice concepts is feasible for internal medicine residents. Residents did not learn detailed knowledge about specific programs for older adults, but clinical geriatrics knowledge improved. PMID- 26279780 TI - Assessing and Documenting the Cognitive Performance of Family Medicine Residents Practicing Outpatient Medicine. AB - BACKGROUND: Development of cognitive skills for competent medical practice is a goal of residency education. Cognitive skills must be developed for many different clinical situations. INNOVATION: We developed the Resident Cognitive Skills Documentation (CogDoc) as a method for capturing faculty members' real time assessment of residents' cognitive performance while they precepted them in a family medicine office. The tool captures 3 dimensions of cognitive skills: medical knowledge, understanding, and its application. This article describes CogDoc development, our experience with its use, and its reliability and feasibility. METHODS: After development and pilot-testing, we introduced the CogDoc at a single training site, collecting all completed forms for 14 months to determine completion rate, competence development over time, consistency among preceptors, and resident use of the data. RESULTS: Thirty-eight faculty members completed 5021 CogDoc forms, documenting 29% of all patient visits by 33 residents. Competency was documented in all entrustable professional activities. Competence was statistically different among residents of different years of training for all 3 dimensions and progressively increased within all residency classes over time. Reliability scores were high: 0.9204 for the medical knowledge domain, 0.9405 for understanding, and 0.9414 for application. Almost every resident reported accessing the individual forms or summaries documenting their performance. CONCLUSIONS: The CogDoc approach allows for ongoing assessment and documentation of resident competence, and, when compiled over time, depicts a comprehensive assessment of residents' cognitive development and ability to make decisions in ambulatory medicine. This approach meets criteria for an acceptable tool for assessing cognitive skills. PMID- 26279781 TI - Workplace-Based Assessment of Internal Medicine Resident Diagnostic Accuracy. AB - BACKGROUND: Making an accurate diagnosis is a core skill residents must develop. Assessments of this skill and decisions to grant residents clinical independence often are based on global impressions. A workplace-based assessment of diagnostic accuracy could be a useful part of a competency-based assessment program and could inform decisions about granting residents independence. INNOVATION: We developed a method for measuring diagnostic accuracy that was integrated into the workflow of internal medicine residents and attending physicians. METHODS: Four senior medical residents and 6 attending physicians working in the internal medicine clinical teaching unit of a tertiary hospital participated in this study. To determine their diagnostic accuracy, residents documented a leading diagnosis for each patient they evaluated in the emergency department. After reviewing each case with the resident and after examining the patient, the resident's attending physician documented the diagnosis. Discharge diagnosis was determined by retrospective chart review to allow determination of resident and attending physician diagnostic accuracy. Data were collected for 240 consecutive patients referred for a medicine consultation. RESULTS: Resident diagnostic accuracy was 66% (95% CI 60-72), whereas attending physician accuracy was significantly higher at 79% (95% CI 74-84, P < .001). By logistic regression, the accuracy of the attending physician was found to be influenced by the accuracy of the resident. Participants felt this process motivated them to improve their clinical reasoning. CONCLUSIONS: Measuring resident diagnostic accuracy provides information that could be used in a competency-based assessment program to provide feedback and motivation to stimulate performance improvement. PMID- 26279782 TI - A Novel Approach to Practice-Based Learning and Improvement Using a Web-Based Audit and Feedback Module. AB - BACKGROUND: Systematically engaging residents in large programs in quality improvement (QI) is challenging. OBJECTIVE: To coordinate a shared QI project in a large residency program using an online tool. METHODS: A web-based QI tool guided residents through a 2-phase evaluation of performance of foot examinations in patients with diabetes. In phase 1, residents completed reviews of health records with online data entry. Residents were then presented with personal performance data relative to peers and were prompted to develop improvement plans. In phase 2, residents again reviewed personal performance. Rates of performance were compared at the program and clinic levels for each phase, with data presented for residents. Acceptability was measured by the number of residents completing each phase. Feasibility was measured by estimated faculty, programmer, and administrator time and costs. RESULTS: Seventy-nine of 86 eligible residents (92%) completed improvement plans and reviewed 1471 patients in phase 1, whereas 68 residents (79%) reviewed 1054 patient charts in phase 2. Rates of performance of examination increased significantly between phases (from 52% to 73% for complete examination, P < .001). Development of the tool required 130 hours of programmer time. Project analysis and management required 6 hours of administrator and faculty time monthly. CONCLUSIONS: An online tool developed and implemented for program-wide QI initiatives successfully engaged residents to participate in QI activities. Residents using this tool demonstrated improvement in a selected quality target. This tool could be adapted by other graduate medical education programs or for faculty development. PMID- 26279783 TI - Expanding Health Policy and Advocacy Education for Graduate Trainees. AB - BACKGROUND: Education in health policy and advocacy is recognized as an important component of health professional training. To date, curricula have only been assessed at the medical school level. OBJECTIVE: We sought to address the gap in these curricula for residents and other health professionals in primary care. INNOVATION: We created a health policy and advocacy curriculum for the VA Connecticut Healthcare System, Center of Excellence in Primary Care Education, an interprofessional, ambulatory-based, training program that includes internal medicine residents, nurse practitioner fellows, health psychology fellows, and pharmacy residents. The policy module focuses on health care finance and delivery, and the advocacy module emphasizes negotiation skills and opinion-based writing. Trainee attitudes were surveyed before and after the course, and using the Wilcoxon signed rank test, relative change was determined. Knowledge acquisition was evaluated with precourse and postcourse examinations using a paired sample t test. RESULTS: From July 2011 through June 2013, 16 trainees completed the course. In the postcourse survey, trainees demonstrated improved comfort with understanding health law and the American health care system (Likert mean increased from 2.1 to 3.0, P = .01), as well as with associated advocacy skills (Likert mean increased from 2.0 to 2.9, P = .04). Knowledge-based test scores also showed significant improvement (increasing from 55% to 78% correct, P <= .001). CONCLUSIONS: Our curriculum integrating core health policy knowledge with advocacy skills represents a novel approach in postgraduate health professional education and resulted in sustained improvement in knowledge and comfort with health policy and advocacy. PMID- 26279784 TI - The Milestones Passport: A Learner-Centered Application of the Milestone Framework to Prompt Real-Time Feedback in the Emergency Department. AB - BACKGROUND: In July 2013, emergency medicine residency programs implemented the Milestone assessment as part of the Next Accreditation System. OBJECTIVE: We hypothesized that applying the Milestone framework to real-time feedback in the emergency department (ED) could affect current feedback processes and culture. We describe the development and implementation of a Milestone-based, learner centered intervention designed to prompt real-time feedback in the ED. METHODS: We developed and implemented the Milestones Passport, a feedback intervention incorporating subcompetencies, in our residency program in July 2013. Our primary outcomes were feasibility, including faculty and staff time and costs, number of documented feedback encounters in the first 2 months of implementation, and user reported time required to complete the intervention. We also assessed learner and faculty acceptability. RESULTS: Development and implementation of the Milestones Passport required 10 hours of program coordinator time, 120 hours of software developer time, and 20 hours of faculty time. Twenty-eight residents and 34 faculty members generated 257 Milestones Passport feedback encounters. Most residents and faculty reported that the encounters required fewer than 5 minutes to complete, and 48% (12 of 25) of the residents and 68% (19 of 28) of faculty reported satisfaction with the Milestones Passport intervention. Faculty satisfaction with overall feedback in the ED improved after the intervention (93% versus 54%, P = .003), whereas resident satisfaction with feedback did not change significantly. CONCLUSIONS: The Milestones Passport feedback intervention was feasible and acceptable to users; however, learner satisfaction with the Milestone assessment in the ED was modest. PMID- 26279785 TI - ACGME Duty Hour Revisions and Self-Reported Intern ICU Sleep Schedules. AB - BACKGROUND: The Accreditation Council for Graduate Medical Education duty hour standards restrict continuous duty for postgraduate year (PGY)-1 residents to 16 hours. OBJECTIVE: We aimed to assess the relationship between a duty hour compliant schedule and resident sleep. METHODS: To comply with 2011 duty hour limits, Beth Israel Deaconess Medical Center restructured its intensive care unit call model for internal medicine PGY-1 residents from a traditional shift model to an overlapping shorter-duration shift model with preserved educational periods. Before and after schedule changes, we used daily surveys of PGY-1 residents to collect self-reported data on quantity and quality of sleep and quality of education. RESULTS: A total of 1162 surveys were sent to 43 interns before scheduling changes, and 1305 were sent to 41 interns after the changes. Response rate was 31.2% (362 of 1161) before and 22.2% (290 of 1305) after. Before changes, 57.7% (209 of 362) reported receiving 6 hours or more of sleep in a 24-hour period compared to 72.4% (210 of 290) after the changes (adjusted relative risk, 1.33; 95% CI, 1.15-1.53), with an adjusted difference of 0.83 hours of sleep per 24 hours (95% CI, 0.28-1.38). After the intervention, on a 5 point Likert scale, residents reported higher quality of sleep (odds ratio [OR], 1.62; 95% CI, 1.01-2.60) and greater satisfaction with their education (OR, 2.59; 95% CI, 1.40-4.81). CONCLUSIONS: Following conversion to a duty hour-compliant model with preserved didactic time, PGY-1 residents reported minor increases in quantity and quality of sleep per 24-hour period, and increased satisfaction with the educational experience. PMID- 26279786 TI - Assessing the Value of Work Done by an Orthopedic Resident During Call. AB - BACKGROUND: Medicare funding for graduate medical education may be cut in the next federal budget. OBJECTIVE: We quantified the value of work that 1 orthopedic surgery resident performs on call and compare it to Medicare educational funding received by the hospital for each resident. METHODS: A single orthopedic resident's on-call emergency department and inpatient consults were collected during a 2-year call period at a large, tertiary, level-1 trauma center. Patient charts were reviewed; ICD-9 codes, evaluation and management, and procedural treatment were recorded. Codes were converted into work relative value units. The number of work relative value units was multiplied by the 2012 Medicare rate of $34.03 per relative value units to calculate the monetary value of resident work. RESULTS: Of 120 resident call shifts, 115 call sheets (95.8%) were available for review, and 1160 patients were seen (average = 10.09 consults/call). A total of 4688 work relative value units were generated (average = 40.76 per night), and the total dollar value generated was $159,561 ($1,387 per call) during the 2 years of call (average = $79,780 annually). Evaluation and management codes generated 2340 work relative value units, with a calculated dollar amount of $79,648, and procedural codes generated 2348 work relative value units, with a calculated dollar amount of $79,913. CONCLUSIONS: Our institution estimated Medicare direct medical education support per resident at $40,000/y, and total funding was $130,000/resident. At our tertiary care institution, the unbilled work of 1 orthopedic resident on call amounts to more than 60% of Medicare direct medical education and indirect medical education funding annually. PMID- 26279787 TI - A Military Transitional Year Professionalism Curriculum. AB - BACKGROUND: Development of professionalism is a critical component of a military transitional year residency. Little published research exists to guide programs in meeting this challenge. OBJECTIVE AND METHODS: After significant concerns regarding resident professionalism were raised by Tripler Army Medical Center faculty, a novel transitional residency professionalism curriculum was conceived and implemented. Universal expectations of physician professionalism, as perceived by various stakeholders (patients, parents, faculty, and nurses), were explored using a small group, discussion-based curriculum. This was combined with a small group, discussion-based, lessons-learned project and a military-unique curriculum. RESULTS: Since implementation, the curriculum has had 100% satisfaction on the part of the faculty and 80% to 100% on the part of the residents, as measured by annual review surveys. Although resident professionalism scores on evaluations did not change significantly, the number of adverse actions because of professionalism lapses has decreased steadily in the 4 years since inception, and the program has been without any such actions for the past 18 months. CONCLUSIONS: Our novel transitional residency professionalism curriculum has been successful in a military residency program. PMID- 26279788 TI - Educational Conference Scheduling, Patient Discharge Time, and Resident Satisfaction. AB - BACKGROUND: Limits on resident duty hours instituted in 2003 and 2011 have compressed medical resident daily workload. Despite this compression, residents must gain competence to practice medicine without supervision. OBJECTIVE: We sought to determine whether moving the time our educational conference is scheduled affects the time when patient discharges are completed on an internal medicine teaching service. METHODS: The study was conducted at a county hospital within a large internal medicine residency program. During the 4-month study period, the morning report conference for internal medicine residents was shifted from 8:30 am to 2 pm. Patient discharge times, defined as the time the discharge order set was signed, were obtained for the service via the electronic health record. The outcomes measured were patient discharge time variation and internal medicine resident preference for conference time. RESULTS: Survey response rate was 82% (42 of 51). Of the residents who responded, 64% (27 of 42) preferred the 8:30 am report time, and 74% (31 of 42) felt the 8:30 am time was also better for education and timing of teaching rounds. There was no difference in discharge times for 2999 patients on the medicine teaching service, whether educational case conference morning report occurred at 8:30 am or at 2 pm. CONCLUSIONS: Medical patient average discharge time was not influenced by time of educational conference. Factors other than the timing of educational conference appear to influence hospital discharge times on an inpatient internal medicine service. PMID- 26279789 TI - Evaluation of Documentation Patterns of Trainees and Supervising Physicians Using Data Mining. AB - BACKGROUND: The electronic health record (EHR) includes a rich data set that may offer opportunities for data mining and natural language processing to answer questions about quality of care, key aspects of resident education, or attributes of the residents' learning environment. OBJECTIVE: We used data obtained from the EHR to report on inpatient documentation practices of residents and attending physicians at a large academic medical center. METHODS: We conducted a retrospective observational study of deidentified patient notes entered over 7 consecutive months by a multispecialty university physician group at an urban hospital. A novel automated data mining technology was used to extract patient note-related variables. RESULTS: A sample of 26 802 consecutive patient notes was analyzed using the data mining and modeling tool Healthcare Smartgrid. Residents entered most of the notes (33%, 8178 of 24 787) between noon and 4 pm and 31% (7718 of 24 787) of notes between 8 am and noon. Attending physicians placed notes about teaching attestations within 24 hours in only 73% (17 843 of 24 443) of the records. Surgical residents were more likely to place notes before noon (P < .001). Nonsurgical faculty were more likely to provide attestation of resident notes within 24 hours (P < .001). CONCLUSIONS: Data related to patient note entry was successfully used to objectively measure current work flow of resident physicians and their supervising faculty, and the findings have implications for physician oversight of residents' clinical work. We were able to demonstrate the utility of a data mining model as an assessment tool in graduate medical education. PMID- 26279790 TI - Using Twitter in Clinical Education and Practice. PMID- 26279791 TI - Moral Distress and Moral Disorientation in the Context of Social Accountability. PMID- 26279792 TI - Does "Quality Time" Improve the Quality of Care? PMID- 26279793 TI - Teaching Wisely. PMID- 26279794 TI - Milestones: Not Millstones but Stepping Stones. PMID- 26279795 TI - Comments: Response to Defining Scholarly Activity. PMID- 26279797 TI - Observations: What Does "Proficient" in Quality Improvement and Patient Safety Look Like? PMID- 26279796 TI - Comments: The Milestones Hypothesis. PMID- 26279799 TI - Memoirs of an ACGME Resident Member. PMID- 26279798 TI - Comments: ACGME Response. PMID- 26279800 TI - The Power of Collaboration: Experiences From the Educational Innovations Project and Implications for the Next Accreditation System. AB - BACKGROUND: The Internal Medicine Educational Innovations Project (EIP) is a 10 year pilot project for innovating in accreditation, which involves annual reporting of information and less-restrictive requirements for a group of high performing programs. The EIP program directors' experiences offer insight into the benefits and challenges of innovative approaches to accreditation as the Accreditation Council for Graduate Medical Education transitions to the Next Accreditation System. OBJECTIVE: We assessed participating program directors' perceptions of the EIP at the midpoint of the project's 10-year life span. METHODS: We conducted telephone interviews with 15 of 18 current EIP programs (83% response rate) using a 19-item, open-ended, structured survey. Emerging themes were identified with content analysis. RESULTS: Respondents identified a number of the benefits from the EIP, most prominent among them, collaboration between programs (87%, 13 of 15) and culture change around quality improvement (47%, 7 of 15). The greatest benefit for residents was training in quality improvement methods (53%, 8 of 15), enhancing those residents' ability to become change agents in their future careers. Although the requirement for annual data reporting was identified by 60% (9 of 15) of program directors as the biggest challenge, respondents also considered it an important element for achieving progress on innovations. Program directors unanimously reported their ability to sustain innovation projects beyond the 10-year participation in EIP. CONCLUSIONS: The work of EIP was not viewed as "more work," but as "different work," which created a new mindset of continuous quality improvement in residency training. Lessons learned offer insight into the value of collaboration and opportunities to use accreditation to foster innovation. PMID- 26279801 TI - Residents' Perspectives on Patient Safety in University and Community Teaching Hospitals. AB - BACKGROUND: Patient safety is an important concept in resident education. To date, few studies have assessed resident perceptions of patient safety across different specialties. OBJECTIVE: The study explored residents' views on patient safety across the specialties of internal medicine, general surgery, and diagnostic radiology, focusing on common themes and differences. METHODS: In fall 2012, interviews of small groups of senior residents in internal medicine, general surgery, and diagnostic radiology were conducted at 3 academic medical centers and 3 community teaching hospitals in 3 major US metropolitan areas. In total, 33 residents were interviewed. Interviews used interactive discussion to explore multiple facets of patient safety. RESULTS: Residents identified lack of information, common errors, volume and acuity of patients, and inadequate supervision as major risks to patient safety. Specific threats to patient safety included communication problems, transitions of care, information technology interface issues, time constraints, and work flow. Residents disclosed that reporting safety issues was viewed as burdensome and carrying some degree of risk. There was variability as to whether residents would report safety threats they encountered. CONCLUSIONS: Residents are aware of threats to patient safety and have a unique perspective compared with other health care professionals. Transitions of care and communication problems were the most common safety threats identified by the residents interviewed. PMID- 26279802 TI - Introducing the CLER Pathways to Excellence: A New Way of Viewing Clinical Learning Environments. PMID- 26279803 TI - CLER Pathways to Excellence: Expectations for an Optimal Clinical Learning Environment (Executive Summary). PMID- 26279805 TI - Erratum. AB - [This corrects the article on p. 243 in vol. 6, PMID: 24701287.]. PMID- 26279804 TI - A Practical Guide to the ACGME Self-Study. PMID- 26279807 TI - Pedicle Screw Placement in the Thoracolumbar Spine Using a Novel, Simple, Safe, and Effective Guide-Pin : A Computerized Tomography Analysis. AB - OBJECTIVE: To improve pedicle screw placement accuracy with minimal radiation and low cost, we developed specially designed K-wire with a marker. To evaluate the accuracy of thoracolumbar pedicle screws placed using the novel guide-pin and portable X-rays. METHODS: Observational cohort study with computerized tomography (CT) analysis of in vivo and in vitro pedicle screw placement. Postoperative CT scans of 183 titanium pedicle screws (85 lumbar and 98 thoracic from T1 to L5) placed into 2 cadavers and 18 patients were assessed. A specially designed guide pin with a marker was inserted into the pedicle to identify the correct starting point (2 mm lateral to the center of the pedicle) and aiming point (center of the pedicle isthmus) in posteroanterior and lateral X-rays. After radiographically confirming the exact starting and aiming points desired, a gearshift was inserted into the pedicle from the starting point into the vertebral body through the center of pedicle isthmus. RESULTS: Ninety-nine percent (181/183) of screws were contained within the pedicle (total 183 pedicle screws : 98 thoracic pedicle screws and 85 lumbar screws). Only two of 183 (1.0%) thoracic pedicle screws demonstrated breach (1 lateral in a patient and 1 medial in a cadaver specimen). None of the pedicle breaches were associated with neurologic or other clinical sequelae. CONCLUSION: A simple, specially designed guide-pin with portable X-rays can provide correct starting and aiming points and allows for accurate pedicle screw placement without preoperative CT scan and intraoperative fluoroscopic assistance. PMID- 26279806 TI - Recent Advancements of Treatment for Leptomeningeal Carcinomatosis. AB - Treatment of Leptomeningeal carcinomatosis (LMC) from solid cancers has not advanced noticeably since the introduction of intra-cerebrospinal fluid (CSF) chemotherapy in the 1970's. The marginal survival benefit and difficulty of intrathecal chemotherapy injection has hindered its wide spread use. Even after the introduction of intraventricular chemotherapy with Ommaya reservoir, frequent development of CSF flow disturbance, manifested as increased intracranial pressure (ICP), made injected drug to be distributed unevenly and thus, the therapy became ineffective. Systemic chemotherapy for LMC has been limited as effective CSF concentration can hardly be achieved except high dose methotrexate (MTX) intravenous administration. However, the introduction of small molecular weight target inhibitors for primary cancer treatment has changed the old concept of 'blood-brain barrier' as the ultimate barrier to systemically administered drugs. Conventional oral administration achieves an effective concentration at the nanomolar level. Furthermore, many studies report that a combined treatment of target inhibitor and intra-CSF chemotherapy significantly prolongs patient survival. Ventriculolumbar perfusion (VLP) chemotherapy has sought to increase drug delivery to the subarachnoid CSF space even in patients with disturbed CSF flow. Recently authors performed phase 1 and 2 clinical trial of VLP chemotherapy with MTX, and 3/4th of patients with increased ICP got controlled ICP and the survival was prolonged. Further trials are required with newly available drugs for CSF chemotherapy. Additionally, new LMC biologic/pharmacodynamic markers for early diagnosis and monitoring of the treatment response are to be identified with the help of advanced molecular biology techniques. PMID- 26279808 TI - The Effect of Early Intervention and Rehabilitation in the Expression of Aquaporin-4; and Ultrastructure Changes on Rat's Offspring's Damaged Brain Caused by Intrauterine Infection. AB - OBJECTIVE: To study the effect of early intervention and rehabilitation in the expression of aquaporin-4 and ultrastructure changes on cerebral palsy pups model induced by intrauterine infection. METHODS: 20 pregnant Wistar rats were consecutively injected with lipopolysaccharide intraperitoneally. 60 Pups born from lipopolysaccharide group were randomly divided into intervention group (n=30) and non-intervention group (n=30); intervention group further divided into early intervention and rehabilitation group (n=10), acupuncture group (n=10) and consolidate group (n=10). Another 5 pregnant rats were injected with normal saline intraperitoneally; 30 pups born from the normal saline group were taken as control group. The intervention group received early intervention, rehabilitation and acupuncture treatment. The motor functions of all pups were assessed via suspension test and modified BBB locomotor score. Aquaporin-4 expression in brain tissue was studied through immunohistochemical and western-blot analysis. Ultrastructure changes in damaged brain and control group were studied electron microscopically. RESULTS: The scores of suspension test and modified BBB locomotor test were significantly higher in the control group than the intervention and non intervention group (p<0.01); higher in the intervention group than the non-intervention group (p<0.01). The expression of Aquaporin-4 was lower in intervention and non intervention group than in the control group (p<0.01); also lower in non-intervention group than the intervention group (p<0.01). Marked changes were observed in ultrastructure of cortex and hippocampus CAI in brain damaged group. CONCLUSION: Early intervention and rehabilitation training can improve the motor function in offspring with brain injury and reduce the expression of aquaporin-4 in damaged brain. PMID- 26279809 TI - Cognitive Dysfunction and Hippocampal Damage Induced by Hypoxic-Ischemic Brain Injury and Prolonged Febrile Convulsions in Immature Rats. AB - OBJECTIVE: Perinatal hypoxic-ischemic encephalopathy (HIE) and prolonged febrile seizures (pFS) are common neurologic problems that occur during childhood. However, there is insufficient evidence from experimental studies to conclude that pFS directly induces hippocampal injury. We studied cognitive function and histological changes in a rat model and investigated which among pFS, HIE, or a dual pathologic effect is most detrimental to the health of children. METHODS: A rat model of HIE at postnatal day (PD) 7 and a pFS model at PD10 were used. Behavioral and cognitive functions were investigated by means of weekly open field tests from postnatal week (PW) 3 to PW7, and by daily testing with the Morris water maze test at PW8. Pathological changes in the hippocampus were observed in the control, pFS, HIE, and HIE+pFS groups at PW9. RESULTS: The HIE priming group showed a seizure-prone state. The Morris water maze test revealed a decline in cognitive function in the HIE and HIE+pFS groups compared with the pFS and control groups. Additionally, the HIE and HIE+pFS groups showed significant hippocampal neuronal damage, astrogliosis, and volume loss, after maturation. The pFS alone induced minimal hippocampal neuronal damage without astrogliosis or volume loss. CONCLUSION: Our findings suggest that pFS alone causes no considerable memory or behavioral impairment, or cellular change. In contrast, HIE results in lasting memory impairment and neuronal damage, gliosis, and tissue loss. These findings may contribute to the understanding of the developing brain concerning conditions caused by HIE or pFS. PMID- 26279810 TI - Clinical Neuropathological Analysis of 10 Cases of Cerebral Amyloid Angiopathy Related Cerebral Lobar Hemorrhage. AB - OBJECTIVE: The clinical and pathological characteristics of 10 cases of cerebral amyloid angiopathy (CAA)-related cerebral lobar hemorrhage (CLH) that was diagnosed at autopsy were investigated to facilitate the diagnosis of this condition. METHODS: The clinical characteristics of 10 cases of CAA-related CLH were retrospectively reviewed, and a neuropathological examination was performed on autopsy samples. RESULTS: The 10 cases included two with a single lobar hemorrhage and eight with multifocal lobar hemorrhages. In all of the cases, the hemorrhage bled into the subarachnoid space. Pathological examinations of the 10 cases revealed microaneurysms in two, double barrel-like changes in four, multifocal arteriolar clusters in five, obliterative onion skin-like intimal changes in four, fibrinoid necrosis of the vessels in seven, neurofibrillary tangles in eight, and senile plaques in five cases. CONCLUSION: CAA-related CLHs were located primarily in the parietal, temporal, and occipital lobes. These hemorrhages normally consisted of multiple repeated CLHs that frequently bled into the subarachnoid space. CAA-associated microvascular lesions may be the pathological factor underlying CLH. PMID- 26279811 TI - Modified Graded Repair of Cerebrospinal Fluid Leaks in Endoscopic Endonasal Transsphenoidal Surgery. AB - OBJECTIVE: Complete sellar floor reconstruction is critical to avoid postoperative cerebrospinal fluid (CSF) leakage during transsphenoidal surgery. Recently, the pedicled nasoseptal flap has undergone many modifications and eventually proved to be valuable and efficient. However, using these nasoseptal flaps in all patients who undergo transsphenoidal surgery, including those who had none or only minor CSF leakage, appears to be overly invasive and time consuming. METHODS: Patients undergoing endoscopic endonasal transsphenoidal tumor surgery within a 5 year-period were reviewed. Since 2009, we classified the intraoperative CSF leakage into grades from 0 to 3. Sellar floor reconstruction was tailored to each leak grade. We did not use any tissue grafts such as abdominal fat and did not include any procedures of CSF diversions such as lumbar drainage. RESULTS: Among 200 cases in 188 patients (147 pituitary adenoma and 41 other pathologies), intraoperative CSF leakage was observed in 27.4% of 197 cases : 14.7% Grade 1, 4.6% Grade 2a, 3.0% Grade 2b, and 5.1% Grade 3. Postoperative CSF leakage was observed in none of the cases. Septal bone buttress was used for Grade 1 to 3 leakages instead of any other foreign materials. Pedicled nasoseptal flap was used for Grades 2b and 3 leakages. Unused septal bones and nasoseptal flaps were repositioned. CONCLUSION: Modified classification of intraoperative CSF leaks and tailored repair technique in a multilayered fashion using an en bloc harvested septal bone and vascularized nasoseptal flaps is an effective and reliable method for the prevention of postoperative CSF leaks. PMID- 26279812 TI - The Change of Sagittal Alignment of the Lumbar Spine after Dynesys Stabilization and Proposal of a Refinement. AB - OBJECTIVE: Dynesys(r) is one of the pedicle-based dynamic lumbar stabilization systems and good clinical outcome has been reported. However, the cylindrical spacer between the heads of the screws undergoes deformation during assembly of the system. The pre-strain probably change the angle of instrumented spine with time and oblique-shaped spacer may reduce the pre-strain. We analyzed patients with single-level stabilization with Dynesys(r) and simulated oblique-shaped spacer with finite element (FE) model analysis. METHODS: Consecutive 14 patients, who underwent surgery for single-level lumbar spinal stenosis and were followed up more than 24 months (M : F=6 : 8; age, 58.7+/-8.0 years), were analyzed. Lumbar lordosis and segmental angle at the index level were compared between preoperation and postoperative month 24. The von Mises stresses on the obliquely cut spacer (5 degrees , 10 degrees , 15 degrees , 20 degrees , 25 degrees , and 30 degrees ) were calculated under the compressive force of 400 N and 10 Nm of moment with validated FE model of the L4-5 spinal motion segment with segmental angle of 16 degrees . RESULTS: Lumbar lordosis was not changed, while segmental angle was changed significantly from -8.1+/-7.2 degrees to -5.9+/-6.7 degrees (p<0.01) at postoperative month 24. The maximum von Mises stresses were markedly decreased with increased angle of the spacer up to 20 degrees . The stress on the spacer was uneven with cylindrical spacer but it became even with the 15 degrees oblique spacer. CONCLUSION: The decreased segmental lordosis may be partially related to the pre-strain of Dynesys. Further clinical and biomechanical studies are required for relevant use of the system. PMID- 26279813 TI - Adolescent Idiopathic Scoliosis Treatment by a Korean Neurosurgeon: The Changing Role for Neurosurgeons. AB - OBJECTIVE: The purpose of this study was to evaluate radiographic/clinical outcomes of adolescent idiopathic scoliosis (AIS) patients treated by a Korean neurosurgeon. METHODS: Ten AIS patients were treated by a single neurosurgeon between January 2011 and September 2013 utilizing segmental instrumentation with pedicle screws. Basic demographic information, curve pattern by Lenke classification, number of levels treated, amount of correction achieved, radiographic/clinical outcomes [by Scolisis Resarch Society (SRS-22r) questionnaire] and complications were evaluated to determine the surgical results. Pulmonary function test was utilized to assess forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) before and after surgery. RESULTS: The average percentage of correction of the major structural curve was 73.6% (ranged from 64% to 81.5%). Preoperative and final postoperative absolute FVC averaged 3.03 L and 3.76 L (0.73 L increase, p=0.046), and absolute FEV1 averaged 2.63 L and 3.49 L (0.86 L increase, p=0.021). Preoperative and final postoperative average self-image and function scores of SRS-22r were, 2.6+/-0.5, 3.3+/-0.1, 4.0+/-0.5, and 4.6+/-0.0, respectively. There was a significant improvement of the self-image and function scores of SRS-22r questionnaires before and after surgery (p<0.05). There was no case of neurological deficit, infection and revision for screw malposition. One patient underwent a fusion extension surgery for shoulder asymmetry. CONCLUSION: Radiographic/clinical outcomes of AIS patients treated by a Korean neurosurgeon were acceptable. Fundamental understanding of pediatric spinal deformity is essential for the practice of AIS surgery. PMID- 26279814 TI - Bone Cement-Augmented Percutaneous Short Segment Fixation: An Effective Treatment for Kummell's Disease? AB - OBJECTIVE: The aim of this prospective study was to evaluate the efficacy of bone cement-augmented percutaneous short segment fixation for treating Kummell's disease accompanied by severe osteoporosis. METHODS: From 2009 to 2013, ten patients with single-level Kummell's disease accompanied by severe osteoporosis were enrolled in this study. After postural reduction for 1-2 days, bone cement augmented percutaneous short segment fixation was performed at one level above, one level below, and at the collapsed vertebra. Clinical results, radiological parameters, and related complications were assessed preoperatively and at 1 month and 12 months after surgery. RESULTS: Prior to surgery, the mean pain score on the visual analogue scale was 8.5+/-1.5. One month after the procedure, this score improved to 2.2+/-2.0 and the improvement was maintained at 12 months after surgery. The mean preoperative vertebral height loss was 48.2+/-10.5%, and the surgical procedure reduced this loss to 22.5+/-12.4%. In spite of some recurrent height loss, significant improvement was achieved at 12 months after surgery compared to preoperative values. The kyphotic angle improved significantly from 22.4+/-4.9 degrees before the procedure to 10.1+/-3.8 degrees after surgery and the improved angle was maintained at 12 months after surgery despite a slight correction loss. No patient sustained adjacent fractures after bone cement augmented percutaneous short segment fixation during the follow-up period. Asymptomatic cement leakage into the paravertebral area was observed in one patient, but no major complications were seen. CONCLUSION: Bone cement-augmented percutaneous short segment fixation can be an effective and safe procedure for Kummell's disease. PMID- 26279815 TI - The Incidence and Management of Dural Tears and Cerebrospinal Fluid Leakage during Corrective Osteotomy for Ankylosing Spondylitis with Kyphotic Deformity. AB - OBJECTIVE: To present the incidence and management of dural tears and cerebrospinal fluid leakage during corrective osteotomy [Pedicle Subtraction Osteotomy (PSO) or Smith-Petersen Osteotomy (SPO)] for ankylosing spondylitis with kyphotic deformity. METHODS: A retrospective study was performed for ankylosing spondylitis patients with fixed sagittal imbalance, who had undergone corrective osteotomy (PSO or SPO) at lumbar level. 87 patients were included in this study. 55 patients underwent PSO, 32 patients underwent SPO. The mean age of the patients at the time of surgery was 41.7 years (21-70 years). Of the 87 patients, 15 patients had intraoperative dural tears. RESULTS: The overall incidence of dural tears was 17.2%. The incidence of dural tears during PSO was 20.0%, SPO was 12.5%. There was significant difference in the incidence of dural tears based on surgical procedures (PSO vs. SPO) (p<0.05). The dural tears ranged in size from 12 to 221 mm(2). A nine of 15 patients had the relatively small dural tears, underwent direct repair via watertight closure. The remaining 6 patients had the large dural tears, consequently direct repair was impossible. The large dural tears were repaired with an on-lay graft of muscle, fascia or fat harvested from the adjacent operation site. All patients had a successful repair with no patient requiring reoperation for the cerebrospinal fluid leak. CONCLUSION: The overall incidence of dural tears during PSO or SPO for ankylosing spondylitis with kyphotic deformity was 17.2%. The risk factor of dural tears was complexity of surgery. All dural tears were repaired primarily using direct suture, muscle, fascia or fat graft. PMID- 26279816 TI - Limited Unilateral Decompression and Pedicle Screw Fixation with Fusion for Lumbar Spinal Stenosis with Unilateral Radiculopathy: A Retrospective Analysis of 25 Cases. AB - OBJECTIVE: Lumbar spinal stenosis is conventionally treated with surgical decompression. However, bilateral decompression and laminectomy is more invasive and may not be necessary for lumbar stenosis patients with unilateral radiculopathy. We aimed to report the outcomes of unilateral laminectomy and bilateral pedicle screw fixation with fusion for patients with lumbar spinal stenosis and unilateral radiculopathy. METHODS: Patients with lumbar spinal stenosis with unilateral lower extremity radiculopathy who received limited unilateral decompression and bilateral pedicle screw fixation were included and evaluated using visual analog scale (VAS) pain and the Oswestry Disability Index (ODI) scores preoperatively and at follow-up visits. Ligamentum flavum thickness of the involved segments was measured on axial magnetic resonance images. RESULTS: Twenty-five patients were included. The mean preoperative VAS score was 6.6+/-1.6 and 4.6+/-3.1 for leg and back pain, respectively. Ligamentum flavum thickness was comparable between the symptomatic and asymptomatic side (p=0.554). The mean follow-up duration was 29.2 months. The pain in the symptomatic side lower extremity (VAS score, 1.32+/-1.2) and the back (VAS score, 1.75+/-1.73) significantly improved (p=0.000 vs. baseline for both). The ODI improved significantly postoperatively (6.60+/-6.5; p=0.000 vs. baseline). Significant improvement in VAS pain and ODI scores were observed in patients receiving single or multi-segment decompression fusion with fixation (p<0.01). CONCLUSION: Limited laminectomy and unilateral spinal decompression followed by bilateral pedicle screw fixation with fusion achieves satisfactory outcomes in patients with spinal stenosis and unilateral radiculopathy. This procedure is less damaging to structures that are important for maintaining posterior stability of the spine. PMID- 26279817 TI - Thoracic Extradural Cavernous Hemangioma Mimicking a Dumbbell-Shaped Tumor. AB - Dumbbell-shaped spinal extradural cavernous hemangioma is rare. The differential diagnosis of dumbbell-shaped spinal tumors based on magnetic resonance imaging includes schwannoma and lymphoma. Here, we report a dumbbell-shaped spinal extradural cavernous hemangioma with intrathoracic growth on T2-3 in a 64-year old man complaining of right side infrascapular area back pain with no neurologic deficit. The cavernous hemangioma was resected through combined video-assisted thoracoscopy and laminectomy without a fusion procedure. The patient had tolerable operative wound pain with no neurologic deficit after surgery. Based on magnetic resonance imaging findings and a review of the literature, we discuss cavernous hemangioma among the differential diagnosis of paravertebral dumbbell shaped spinal tumors and the importance of complete resection. PMID- 26279818 TI - Unexpected Severe Cerebral Edema after Cranioplasty : Case Report and Literature Review. AB - This report details a case of unexpected, severe post-operative cerebral edema following cranioplasty. We discuss the possible pathological mechanisms of this complication. A 50-year-old female was admitted to our department with sudden onset of stuporous consciousness. A brain computed tomography (CT) revealed a subarachnoid hemorrhage with intracranial hemorrhage and subdural hematoma. Emergency decompressive craniectomy and aneurysmal neck clipping were performed. Following recovery, the decision was made to proceed with an autologous cranioplasty. The cranioplasty procedure was free of complications. An epidural drain was placed and connected to a suction system during skin closure to avoid epidural blood accumulation. However, following the procedure, the patient had a seizure in the recovery room. An emergency brain CT scan revealed widespread cerebral edema, and the catheter drain was clamped. The increased intracranial pressure and cerebral edema were controlled with osmotic diuretics, corticosteroids, and antiepileptic drugs. The edema slowly subsided, but new low density areas were noted in the brain on follow-up CT 1 week later. We speculated that placing the epidural drain on active suction may have caused an acute decrease in intracranial pressure and subsequent rapid expansion of the brain, which impaired autoregulation and led to reperfusion injury. PMID- 26279819 TI - Cranioplasty Using a Modified Split Calvarial Graft Technique in Cleidocranial Dysplasia. AB - Cleidocranial dysplasia is a well-documented rare autosomal dominant skeletal dysplasia characterized by hypoplastic/aplastic clavicles, brachycephalic skull, patent sutures and fontanelles, midface hypoplasia, and abnormalities of dentition. Patients with cleidocranial dysplasia often complain about undesirable esthetic appearance of their forehead and skull. Notwithstanding many studies of molecular, genetics and skeletal abnormalities of this congenial disorder, there have been very few written reports of cranioplasty involving cleidocranial dysplasia. Thus, we report a rare case of successful cranioplasty using a modified split calvarial graft technique in patient with cleidocranial dysplasia. PMID- 26279820 TI - Growing Organized Hematomas Following Gamma Knife Radiosurgery for Cerebral Arteriovenous Malformation : Five Cases of Surgical Excision. AB - Organized hematoma is a rare complication that can develop following gamma knife radiosurgery (GKS) for cerebral arteriovenous malformation (AVM). Here, we describe 5 patients with growing organized hematomas that developed from completely obliterated AVMs several years after GKS. The patients were 15, 16, 30, 36, and 38 years old at the time of GKS, respectively, and 3 patients were female. Four AVMs were located in the lobe of the brain, and the remaining AVM were in the thalamus. Between 2-12 years after GKS, patients developed progressive symptoms such intractable headache or hemiparesis and enhancing mass lesions were identified. Follow-up visits revealed the slow expansion of the hematomas and surrounding edema. Steroids were ineffective, and thus surgery was performed. Histology revealed organized hematomas with a capsule, but there was no evidence of residual AVMs or vascular malformation. After surgery, the neurological symptoms of all patients improved and the surrounding edema resolved. However, the hematoma continued to expand and intraventricular hemorrhage developed in 1 patient whose hematoma was only partially removed. GKS for cerebral AVM can be complicated by growing, organized hematomas that develop after complete obliteration. Growing hematomas should be surgically evacuated if they are symptomatic. Radical resection of the hematoma capsule is also strongly recommended. PMID- 26279821 TI - Successful Treatment of Occipital Radiating Headache Using Pulsed Radiofrequency Therapy. AB - Rheumatoid arthritis (RA) is a chronic inflammatory disease involving multiple joints. The cervical spine is often affected, and cases involving atlantoaxial joint can lead to instability. Anterior atlantoaxial subluxation in RA patients can lead to posterior neck pain or occipital headache because of compression of the C2 ganglion or nerve. Here, we report the successful treatment of a RA patient with occipital radiating headache using pulsed radiofrequency therapy at the C2 dorsal root ganglion. PMID- 26279822 TI - Management of neurogenic bladder. PMID- 26279823 TI - Urologic robotic surgery in Korea: past and present. AB - Since 2005 when the da Vinci surgical system was approved as a medical device by the Korean Ministry of Health and Welfare, 51 systems have been installed in 40 institutions as of May 2015. Although robotic surgery is not covered by the national health insurance service in Korea, it has been used in several urologic fields as a less invasive surgery. Since the first robotic-assisted laparoscopic radical prostatectomy in 2005, partial nephrectomy, radical cystectomy, pyeloplasty, and other urologic surgeries have been performed. The following should be considered to extend the indications for robotic surgery: training systems including accreditation, operative outcomes from follow-up results, and cost-effectiveness. In this review, the history and current status of robotic surgeries in Korea are presented. PMID- 26279824 TI - New and contemporary markers of prognosis in nonmuscle invasive urothelial cancer. AB - Nonmuscle invasive (NMI) urothelial cancer (UC) is associated with varied biological potential. It is characterized by frequent recurrence and progression, which thus worsens the oncological outcome. Nearly three-quarters of NMI UCs recur within 5 years, whereas half can progress during follow-up. Progression is particularly seen in T1 and carcinoma in situ (CIS). Undoubtedly, NMI UC is one of the most expensive cancers to manage. The European Organisation for Research and Treatment of Cancer (EORTC) risk calculator is a commonly used tool for assessing the recurrence and progression potential of a newly diagnosed cancer. The parameters used in the assessment are tumor size and number, pathological stage and grade of the cancer, presence of CIS, and prior recurrence rate. The main advantages of the EORTC tool are its ease of use and the lack of need to run expensive molecular tests. However, reproducibility of pathologic stage and grade is modest, which is a concern to clinicians. Molecular markers have potential for predicting the clinical outcome of NMI UC, given that clinico-pathologic variables are not sufficient for prediction of prognosis in an individual. Significant work has been done in the past 2 decades in understanding the molecular biology of bladder cancer; however, the translational value of this knowledge remains poor. The role for molecular markers in predicting recurrence seems limited because multifocal disease and incomplete treatment are probably more important for recurrence than the molecular features of a resected tumor. Urinary markers have very limited value in prognostication of bladder cancer and are used (mainly as an adjunct to cytology) for detection and surveillance of urothelial cell cancer recurrence. Prediction of progression with molecular markers holds considerable promise. Nevertheless, the contemporary value of molecular markers over clinico-pathologic indexes is limited. PMID- 26279825 TI - Clinical features and prognosis of prostate cancer with high-grade prostatic intraepithelial neoplasia. AB - PURPOSE: To evaluate the clinical features and biochemical recurrence (BCR) in prostate cancer (PCa) with high-grade prostatic intraepithelial neoplasia (HGPIN). MATERIALS AND METHODS: We retrospectively analyzed the medical records of 893 patients who underwent a radical prostatectomy for PCa between 2011 and 2012 at Asan Medical Center; 752 of these patients who did not receive neoadjuvant or adjuvant therapy and were followed up for more than 1 year were included. The cohort was divided into two groups-patients with and without HGPIN and their characteristics were compared. The Cox proportional hazards model was used to analyze factors affecting BCR. RESULTS: In total, 652 study patients (86.7%) had HGPIN. There were no significant differences in preoperative factors between the two groups, including age (p=0.369) and preoperative prostate specific antigen concentration (p=0.234). Patients with HGPIN had a higher Gleason score (p=0.012), more frequent multiple tumor (p=0.013), and more perineural invasion (p=0.012), but no other postoperative pathologic characteristics were significantly different between the two groups. There were no significant differences in BCR (13.0% vs. 11.5%, p=0.665) and HGPIN was not associated with BCR (p=0.745). In multivariate analysis, only the T stage (p<0.001) was associated with BCR. CONCLUSIONS: PCa patients with HGPIN have a higher Gleason score, more frequent multiple tumors, and more perineural invasion than those without HGPIN. The presence of HGPIN is not an independent predictor of BCR. PMID- 26279826 TI - Comparative analysis of oncologic outcomes for open vs. robot-assisted radical prostatectomy in high-risk prostate cancer. AB - PURPOSE: To evaluate the oncologic outcomes of robot-assisted radical prostatectomy (RARP) in high-risk prostate cancer (PCa), we compared the surgical margin status and biochemical recurrence-free survival (BCRFS) rates between retropubic radical prostatectomy (RRP) and RARP. MATERIALS AND METHODS: A comparative analysis was conducted of high-risk PCa patients who underwent RRP or RARP by a single surgeon from 2007 to 2013. High-risk PCa was defined as clinical stage>=T3a, biopsy Gleason score 8-10, or prostate-specific antigen>20 ng/mL. Propensity score matching was performed to minimize selection bias, and all possible preoperative and postoperative confounders were matched. A Kaplan-Meier analysis was performed to assess the 5-year BCRFS, and Cox regression models were used to evaluate the effect of the surgical approach on biochemical recurrence. RESULTS: A total of 356 high-risk PCa patients (106 [29.8%] RRP and 250 [70.2%] RARP) were included in the final cohort analyzed. Before adjustment, the mean percentage of positive cores on biopsy and pathologic stage were poorer for RRP versus RARP (p=0.036 vs. p=0.054, respectively). The unadjusted 5-year BCRFS rates were better for RARP than for RRP (RRP vs. RARP: 48.1% vs. 64.4%, p=0.021). After adjustment for preoperative variables, the 5-year BCRFS rates were similar between RRP and RARP patients (48.5% vs. 59.6%, p=0.131). The surgical approach did not predict biochemical recurrence in multivariate analysis. CONCLUSIONS: Five-year BCRFS rates of RARP are comparable to RRP in high-risk PCa. RARP is a feasible treatment option for high-risk PCa. PMID- 26279827 TI - Clinical effect of abiraterone acetate in Korean patients with metastatic castration-resistant prostate cancer according to duration of androgen deprivation therapy. AB - PURPOSE: Few data are available concerning the clinical outcome of abiraterone acetate treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) in terms of the duration of androgen deprivation therapy (ADT) before diagnosis of CRPC. We investigated the clinical efficacy of abiraterone acetate according to the duration of ADT. MATERIALS AND METHODS: We reviewed the medical records of 20 patients with mCRPC who received abiraterone acetate after failure of docetaxel chemotherapy from May 2012 to March 2014 at Seoul National University Bundang Hospital. Clinical factors including prostate-specific antigen (PSA) nadir level, time to PSA nadir, PSA doubling time, PSA response, and modes of progression (PSA, radiologic, clinical) were analyzed. Disease progression was classified according to the Prostate Cancer Working Group 2 criteria. RESULTS: The mean age and PSA value of the entire cohort were 76.0+/-7.2 years and 158.8+/ 237.9 ng/mL, respectively. The median follow-up duration was 13.4+/-6.7 months. There were no statistically significant differences in clinical characteristics between patients who received abiraterone acetate with ADT duration<35 months and those who received abiraterone acetate with ADT duration>=35 months. There were also no significant differences in terms of PSA progression-free survival, radiologic progression-free survival, and clinical progression-free survival between patients with ADT duration<35 months and those with ADT duration >=35 months. CONCLUSIONS: Although this was a retrospective study with a small sample size, we did not observe any statistically significant differences in the clinical response to abiraterone acetate between mCRPC patients with long ADT duration and those with short ADT duration in terms of disease progression-free survival. PMID- 26279828 TI - Evaluation of low-dose dual energy computed tomography for in vivo assessment of renal/ureteric calculus composition. AB - PURPOSE: This study aimed to assess the accuracy of low-dose dual-energy computed tomography (DECT) in predicting the composition of urinary calculi. MATERIALS AND METHODS: A total of 52 patients with urinary calculi were scanned with a 128 slice dual-source DECT scanner by use of a low-dose protocol. Dual-energy (DE) ratio, weighted average Hounsfield unit (HU) of calculi, radiation dose, and image noise levels were recorded. Two radiologists independently rated study quality. Stone composition was assessed after extraction by Fourier transform infrared spectroscopy (FTIRS). Analysis of variance was used to determine if the differences in HU values and DE ratios between the various calculus groups were significant. Threshold cutoff values to classify the calculi into separate groups were identified by receiver operating characteristic curve analysis. RESULTS: A total of 137 calculi were detected. FTIRS analysis differentiated the calculi into five groups: uric acid (n=17), struvite (n=3), calcium oxalate monohydrate and dihydrate (COM-COD, n=84), calcium oxalate monohydrate (COM, n=28), and carbonate apatite (n=5). The HU value could differentiate only uric acid calculi from calcified calculi (p<0.001). The DE ratio could confidently differentiate uric acid, struvite, calcium oxalate, and carbonate apatite calculi (p<0.001) with cutoff values of 1.12, 1.34, and 1.66, respectively, giving >80% sensitivity and specificity to differentiate them. The DE ratio could not differentiate COM from COM-COD calculi. No study was rated poor in quality by either of the observers. The mean radiation dose was 1.8 mSv. CONCLUSIONS: Low-dose DECT accurately predicts urinary calculus composition in vivo while simultaneously reducing radiation exposure without compromising study quality. PMID- 26279830 TI - Letter to the editor: predictive value of the neutrophil-lymphocyte ratio and mean platelet volume in testicular torsion. PMID- 26279829 TI - Inpatients hypospadias care: trends and outcomes from the American nationwide inpatient sample. AB - PURPOSE: Hypospadias is the most common congenital penile anomaly. Information about current utilization patterns of inpatient hypospadias repair as well as complication rates remain poorly evaluated. MATERIALS AND METHODS: The Nationwide Inpatient Sample was used to identify all patients undergoing inpatient hypospadias repair between 1998 and 2010. Patient and hospital characteristics were attained and outcomes of interest included intra- and immediate postoperative complications. Utilization was evaluated temporally and also according to patient and hospital characteristics. Predictors of complications and excess length of stay were evaluated by logistic regression models. RESULTS: A weighted 10,201 patients underwent inpatient hypospadias repair between 1998 and 2010. Half were infants (52.2%), and were operated in urban and teaching hospitals. Trend analyses demonstrated a decline in incidence of inpatient hypospadias repair (estimated annual percentage change, -6.80%; range, -0.51% to 12.69%; p=0.037). Postoperative complication rate was 4.9% and most commonly wound-related. Hospital volume was inversely related to complication rates. Specifically, higher hospital volume (>31 cases annually) was the only variable associated with decreased postoperative complications. CONCLUSIONS: Inpatient hypospadias repair have substantially decreased since the late 1990's. Older age groups and presumably more complex procedures constitute most of the inpatient procedures nowadays. PMID- 26279831 TI - The authors reply: Predictive role of hematologic parameters in testicular torsion. PMID- 26279832 TI - Atypical emotional anticipation in high-functioning autism. AB - BACKGROUND: Understanding and anticipating others' mental or emotional states relies on the processing of social cues, such as dynamic facial expressions. Individuals with high-functioning autism (HFA) may process these cues differently from individuals with typical development (TD) and purportedly use a 'mechanistic' rather than a 'mentalistic' approach, involving rule- and contingency-based interpretations of the stimuli. The study primarily aimed at examining whether the judgments of facial expressions made by individuals with TD and HFA would be similarly affected by the immediately preceding dynamic perceptual history of that face. A second aim was to explore possible differences in the mechanisms underpinning the perceptual judgments in the two groups. METHODS: Twenty-two adults with HFA and with TD, matched for age, gender and IQ, were tested in three experiments in which dynamic, 'ecologically valid' offsets of happy and angry facial expressions were presented. Participants evaluated the expression depicted in the last frame of the video clip by using a 5-point scale ranging from slightly angry via neutral to slightly happy. Specific experimental manipulations prior to the final facial expression of the video clip allowed examining contributions of bottom-up mechanisms (sequential contrast/context effects and representational momentum) and a top-down mechanism (emotional anticipation) to distortions in the perception of the final expression. RESULTS: In experiment 1, the two groups showed a very similar perceptual bias for the final expression of joy-to-neutral and anger-to-neutral videos (overshoot bias). In experiment 2, a change in the actor's identity during the clip removed the bias in the TD group, but not in the HFA group. In experiment 3, neutral-to joy/anger-to-neutral sequences generated an undershoot bias (opposite to the overshoot) in the TD group, whereas no bias was observed in the HFA group. CONCLUSIONS: We argue that in TD individuals the perceptual judgments of other's facial expressions were underpinned by an automatic emotional anticipation mechanism. In contrast, HFA individuals were primarily influenced by visual features, most notably the contrast between the start and end expressions, or pattern extrapolation. We critically discuss the proposition that automatic emotional anticipation may be induced by motor simulation of the perceived dynamic facial expressions and discuss its implications for autism. PMID- 26279834 TI - Effects of dietary protein/energy ratio on growth performance, carcass trait, meat quality, and plasma metabolites in pigs of different genotypes. AB - BACKGROUND: The protein/energy ratio is important for the production performance and utilization of available feed resources by animals. Increased protein consumption by mammals leads to elevated feed costs and increased nitrogen release into the environment. This study aimed to evaluate the effects of dietary protein/energy ratio on the growth performance, carcass traits, meat quality, and plasma metabolites of pigs of different genotypes. METHODS: Bama mini-pigs and Landrace pigs were randomly assigned to two dietary treatment groups (Chinese conventional diet with low protein/energy ratio or National Research Council diet with high protein/energy ratio; n = 24 per treatment) in a 2 * 2 factorial arrangement. Blood and muscle samples were collected at the end of the nursery, growing, and finishing phases. RESULTS: We observed significant interactions (P < 0.05) between breed and diet for total fat percentage, intramuscular fat (IMF) content, protein content in biceps femoris (BF) muscle, and plasma urea nitrogen (UN) concentration in the nursery phase; for average daily gain (ADG), average daily feed intake (ADFI), dry matter, IMF content in psoas major (PM) muscle, and plasma total protein and albumin concentrations in the growing phase; and for drip loss and plasma UN concentration in the finishing phase. Breed influenced (P < 0.05) growth performance, carcass traits, and meat quality, but not plasma metabolites. Throughout the trial, Landrace pigs showed significantly higher (P < 0.05) ADG, ADFI, dressing percentage, lean mass rate, and loin-eye area than did Bama mini-pigs, but significantly lower (P < 0.05) feed/gain ratio, fat percentage, backfat thickness, and IMF content. Dietary protein/energy ratio influenced the pH value, chemical composition of BF and PM muscles, and plasma activities of glutamic-pyruvic transaminase and gamma-glutamyl transpeptidase, and plasma concentration of UN. CONCLUSIONS: Compared with Landrace pigs, Bama mini-pigs showed slower growth and lower carcass performance, but had better meat quality. Moreover, unlike Landrace pigs, the dietary protein/energy ratio did not affect the growth performance of Bama mini-pigs. These results suggest that, in swine production, low dietary protein/energy ratio may be useful for reducing feed costs and minimizing the adverse effects of ammonia release into the environment. PMID- 26279835 TI - Hypo-endemic onchocerciasis hotspots: defining areas of high risk through micro mapping and environmental delineation. AB - BACKGROUND: Onchocerciasis (river blindness) caused by the parasite Onchocercavolvulus and transmitted by riverine Simulium spp. (Black flies) is targeted for elimination in Africa. This is a significant change in strategy from the 'control' of meso- and hyper-endemic areas through mass drug administration (MDA) with Mectizan(r) (ivermectin), to the 'elimination' in all endemic areas where a range of interventions may be required. The most significant challenges of elimination in low transmission or hypo-endemic areas are two-fold. First, there are vast remote areas where the focality of low transmission is relatively undefined. Second, the treatment with ivermectin increases the risk of serious adverse events (SAEs) in individuals with high parasitaemias of Loa loa, a filarial parasite widespread in Central and West Africa, which causes Tropical eye worm and transmitted by Chrysops spp. (Deer flies). DISCUSSION: We therefore propose novel mapping approaches using remote sensing satellite and modelled environmental data to be used in combination with rapid field surveys to help resolve the problems of targeting the expansion of onchocerciasis elimination activities in L. loa co-endemic areas. First, we demonstrate that micro stratification overlap mapping (MOM) of available onchocerciasis and loiasis prevalence maps can be used to identify 12 key high risk areas, where low O. volvulusand high L. loa transmission overlap, which we define as "hypo-endemic hotspots". Second we show that integrated micro-mapping of prevalence data, and the use of environmental data to delineate riverine and forest risk factors associated with Simulium spp. and Chrysops spp. vector habitats can further help to define target intervention areas i.e. secondary hotspots within hotspots, to help avoid the risk of SAEs. SUMMARY: These mapping examples demonstrate the value of bringing prevalence, entomological and ecological information together to develop maps for planned implementation and targeted strategies. This is critical as better mapping may the reduce costs and lower the L. loa associated risks, especially if there are extensive areas of low endemicity that may require treatment with ivermectin or alternative strategies. Novel cost-effective approaches are necessary if elimination of O.volvulus transmission in Africa is to be achieved in an efficient and safe way by the goal of 2025. PMID- 26279833 TI - Sex differences in the brain: a whole body perspective. AB - Most writing on sexual differentiation of the mammalian brain (including our own) considers just two organs: the gonads and the brain. This perspective, which leaves out all other body parts, misleads us in several ways. First, there is accumulating evidence that all organs are sexually differentiated, and that sex differences in peripheral organs affect the brain. We demonstrate this by reviewing examples involving sex differences in muscles, adipose tissue, the liver, immune system, gut, kidneys, bladder, and placenta that affect the nervous system and behavior. The second consequence of ignoring other organs when considering neural sex differences is that we are likely to miss the fact that some brain sex differences develop to compensate for differences in the internal environment (i.e., because male and female brains operate in different bodies, sex differences are required to make output/function more similar in the two sexes). We also consider evidence that sex differences in sensory systems cause male and female brains to perceive different information about the world; the two sexes are also perceived by the world differently and therefore exposed to differences in experience via treatment by others. Although the topic of sex differences in the brain is often seen as much more emotionally charged than studies of sex differences in other organs, the dichotomy is largely false. By putting the brain firmly back in the body, sex differences in the brain are predictable and can be more completely understood. PMID- 26279836 TI - International training programs on eating disorders for professionals, caregivers, and the general public: A scoping review. AB - This review identified and synthesized published training programs on eating disorders (ED) (anorexia nervosa or bulimia nervosa) for professionals, natural supporters of people with ED, or the public. A scoping review using the Arksey and O'Malley (2005) framework was conducted. Four data bases were searched, for all years, and manual searches from three additional sources were also conducted. Experts on ED were consulted for validation of the identified studies. A narrative synthesis was performed. A total of 20 evaluation studies from five countries were identified, and reviewed in relation to 14 ED training programs. Characteristics of the training programs, and study characteristics, were highly diverse, as shown on Table 1 which compiles results from the charted data. Evaluations were equally divided between training for healthcare and education professionals (9), and training for families or other carers of people with ED (10). One study evaluated ED training for the general public. We found that training orientation varies with the interests and needs of different trainee groups. While most studies assessed trainee outcomes, future research needs to give greater consideration to patient perspectives, and to the relationship between training and evaluation approaches, improved knowledge, and better care. PMID- 26279837 TI - Religiosity, spirituality in relation to disordered eating and body image concerns: A systematic review. AB - OBJECTIVE: This systematic review aims to critically examine the existing literature that has reported on the links between aspects of religiosity, spirituality and disordered eating, psychopathology and body image concerns. METHOD: A systematic search of online databases (PsycINFO, Medline, Embase and Web of Science) was conducted in December 2014. A search protocol was designed to identify relevant articles that quantitatively explored the relationship between various aspects of religiosity and/or spirituality and disordered eating, psychopathology and/or body image concerns in non-clinical samples of women and men. RESULTS: Twenty-two studies were identified to have matched the inclusion criteria. Overall, the main findings to emerge were that strong and internalised religious beliefs coupled with having a secure and satisfying relationship with God were associated with lower levels of disordered eating, psychopathology and body image concern. Conversely, a superficial faith coupled with a doubtful and anxious relationship with God were associated with greater levels of disordered eating, psychopathology and body image concern. DISCUSSION: While the studies reviewed have a number of evident limitations in design and methodology, there is sufficient evidence to make this avenue of enquiry worth pursuing. It is hoped that the direction provided by this review will lead to further investigation into the protective benefits of religiosity and spirituality in the development of a clinical eating disorder. Thus a stronger evidence base can then be utilised in developing community awareness and programs which reduce the risk. PMID- 26279838 TI - Application of the Barcelona Clinic Liver Cancer therapeutic strategy and impact on survival. AB - BACKGROUND: The Barcelona Clinic Liver Cancer (BCLC) classification of hepatocellular carcinoma (HCC) has proved useful in the management of HCC patients. However, BCLC-recommended first-line treatment is not always applicable in clinical practice. OBJECTIVE: We performed a multicentre retrospective analysis of reasons for deviation from first-line treatment in 2008-2012. METHODS: One to three-year survival data were analysed using Kaplan-Meier method. RESULTS: A total of 407 consecutive HCC patients (66.6 +/- 3 years, 83% male) with cirrhosis were included. Tumours were detected during surveillance in 53% of patients, grouped as Child-Pugh A (67%), B (25%) and C (8%); and BCLC A (including stage 0, 44%), B (26%), C (15%) and D (15%). In 31% of patients, first line treatment was not feasible (51% in early stages) due to: technical reasons (74%); patient non-conformity (20%); medical decision (3%); and disease progression (3%). One to three-year survival of patients not receiving the recommended first-line treatment was similar to that of patients treated according to BCLC recommendations (log-rank, p = 0.229). CONCLUSION: In real-life practice one-third of HCC patients could not receive first-line BCLC treatment. In our cohort of patients, similar short and medium-term survival was observed. Long-term prospective studies are required to determine the best alternative treatment option when BCLC first-line treatment is not feasible. PMID- 26279839 TI - Emerging indications of endoscopic radiofrequency ablation. AB - INTRODUCTION: Radiofrequency ablation (RFA) is a well-validated treatment of dysplastic Barrett's esophagus. Other indications of endoscopic RFA are under evaluation. RESULTS: Four prospective studies (total 69 patients) have shown that RFA achieved complete remission of early esophageal squamous intra-epithelial neoplasia at a rate of 80%, but with a substantial risk of stricture. In the setting of gastric antral vascular ectasia, two prospective monocenter studies, and a retrospective multicenter study, (total 51 patients), suggest that RFA is efficacious in terms of reducing transfusion dependency. In the setting of chronic hemorrhagic radiation proctopathy, a prospective monocenter study and a retrospective multicenter study (total 56 patients) suggest that RFA is an efficient treatment. A retrospective comparative study (64 patients) suggests that RFA improves stents patency in malignant biliary strictures. CONCLUSIONS: Endoscopic RFA is an upcoming treatment modality in early esophageal squamous intra-epithelial neoplasia, as well as in gastric, rectal, and biliary diseases. PMID- 26279840 TI - Systematic review and meta-analysis: Efficacy and safety of POEM for achalasia. AB - BACKGROUND: Peroral endoscopic esophageal myotomy (POEM) represents a less invasive alternative, as compared with conventional laparoscopic Heller myotomy for treating achalasia patients. In the last years, a number of prospective and retrospective experiences with POEM use for achalasia have been published. METHODS: Relevant publications in which patients affected by achalasia underwent POEM treatment were identified by PubMed databases for the period 2010 - 2013. From each study, we extracted the number and type of major complications (defined as those requiring any additional medical or surgical intervention). Data were pooled, using random-effects models. Heterogeneity among studies was assessed by using Cochran's Q and the I (2) statistic. RESULTS: We found 16 studies that provided data on 551 patients. The median surveillance period was 6 months (range: 3-12). The median of mean POEM duration was 156 minutes (range: 42-112). Median myotomy length was 10 cm (range: 6-14). Technical and clinical success were reported in 97% (95% CI: 94-98%) and 93% (407/428; 95% CI: 90-95%). No heterogeneity (I (2 )= 0%) or publication bias was present in both estimates. When limiting the analysis only to adverse events that require medical or surgical interventions, major adverse events occurred in 14% (95% CI: 11-17%); however, only one patient needed post-POEM surgery (0.2%; 95% CI: 0-0.5%). CONCLUSIONS: POEM appeared to be a highly feasible and effective endoscopic treatment for achalasia. Despite POEM being apparently associated with relatively high morbidity, most patients are successfully managed conservatively, so that POEM appears as a very safe procedure; however, POEM should only be performed in centers able to treat POEM complications, such as pneumothorax or pneumoperitoneum. PMID- 26279841 TI - IBD-related work disability in the community: Prevalence, severity and predictive factors. A cross-sectional study. AB - BACKGROUND AND AIMS: Data on the prevalence of work disability in patients with inflammatory bowel disease (IBD) are heterogeneous. As most studies have been performed in selected, often severe, IBD patients, the true prevalence of disability in the community remains controversial. The aim of this cross sectional study was to evaluate the prevalence and severity of disability and its predictive factors in a community-based IBD population. PATIENTS AND METHODS: Patients recorded in the community-based IBD register at the Hospital Universitario de Burgos were contacted. After informed consent they completed a set of questionnaires including demographic, clinical, disability and quality of life data. The statistical study was performed using SPSS 21. RESULTS: A total of 293 patients were included - 151 Crohn's disease (CD), 142 ulcerative colitis (UC), 137 female, mean age: 45 +/- 11 years, mean time since diagnosis: 10.6 +/- 11 years. Twelve patients (4.1%) had a work-disability pension. In addition, 93 (32%) of all patients had an officially recognized disability degree, which was generally moderate (n = 73, 25%) or severe (N = 16, 5%). Age, time since IBD diagnosis, CD, perianal disease, incontinence, active disease, the need for anti TNF or psychological treatment, previous surgeries and the number of diagnostic tests and medical visits in the previous year were predictors of disability. Major predictors of qualifying for a disability pension were age, IBD activity, incontinence, need for biological drugs and ostomy. CONCLUSION: Mild to moderate work disability is frequent in IBD. However, only a minority of patients develop severe disability qualifying them for a pension. PMID- 26279842 TI - Comparison of 22G reverse-beveled versus standard needle for endoscopic ultrasound-guided sampling of solid pancreatic lesions. AB - OBJECTIVES: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) using standard needles has a high diagnostic value in the evaluation of solid pancreatic masses. Fenestrated needles have been developed to improve the quality of EUS-guided tissue sampling by providing core biopsies (FNB). METHODS: Patients with solid pancreatic masses of >2 cm were prospectively included in our study and randomized to receive EUS sampling, using either a standard 22G FNA or a 22G Procore(r) FNB needle. The main study endpoint was the number of needle passes required to obtain a diagnosis in more than 90% of cases. RESULTS: We included 100 patients (male = 63, female = 37; mean age = 68.4 years) in our study. We found that 88% of the lesions were malignant, with a mean size of 32 mm. A sample adequate for diagnosis was obtained in more than 90% of cases after the second needle pass in the FNB group, versus the third needle pass in the FNA group. Slide cellularity and presence of tissue microfragments were significantly higher in the FNB group. Sensitivity for the diagnosis of malignancy was 88.4% versus 97.8% for the EUS-FNA and EUS-FNB group, respectively, while specificity for both techniques was 100%. No complications were recorded. CONCLUSIONS: Although the accuracy of both needle types for proving malignancy was similar, a lower number of passes was required with the FNB needles to achieve the same contributive sample rate as with the FNA needles. FNB also improved the histopathological quality of specimens, suggesting an overall superiority of FNB sampling. PMID- 26279843 TI - Is there a proximal shift in the distribution of colorectal adenomas? AB - INTRODUCTION: Several studies have shown a proximal shift of colorectal cancer (CRC) during the last decades. However, few have analyzed the changing distribution of adenomas over time. AIM: The aim of this study was to compare the site and the characteristics of colorectal adenomas, in a single center, during two periods. METHODS: We conducted a retrospective, observational study in a single hospital of adenomas removed during a total colonoscopy in two one-year periods: 2003 (period 1) and 2012 (period 2). Patients with inflammatory bowel disease, familial adenomatous polyposis, hereditary non-polyposis colorectal cancer syndrome, or history of CRC were excluded from the study. The chi(2) statistical test was performed. P values less than 0.05 were considered statistically significant. RESULTS: During the two considered periods, a total of 864 adenomas from 2394 complete colonoscopies were analyzed: 333 adenomas from 998 colonoscopies during period 1 and 531 adenomas from 1396 colonoscopies during period 2. There was a significant increase in the proportion of adenomatous polyps in the proximal colon from period 1 to 2 (30.6% to 38.8% (p = 0.015)). Comparing the advanced features of adenomas between the two periods, it was noted that in period 2, the number of adenomas with size >=1 cm (p = 0.001), high-grade dysplasia (p = 0.001), and villous features (p < 0.0001) had a significant increase compared to period 1. CONCLUSION: Incidence of adenomatous polyps in the proximal colon as well as adenomas with advanced features has increased in the last years. This finding may have important implications regarding methods of CRC screening. PMID- 26279844 TI - The safety of same-day CT colonography following incomplete colonoscopy with polypectomy. AB - BACKGROUND: Concerns about the risk of bowel perforation for same-day computed tomography colonography (CTC) following an incomplete colonoscopy with polypectomy may lead to unnecessarily postponing the CTC. OBJECTIVE: The objective of this article is to describe the complications including colon perforations associated with same-day CTC in a cohort who had polypectomies but an incomplete colonoscopy. DESIGN: We conducted a retrospective study. SETTING: Our study took place in a single, tertiary referral center. PATIENTS: We studied consecutive patients who had CTC the same day as an incomplete colonoscopy with polypectomy. INTERVENTIONS: Interventions included optical colonoscopy (OC), endoscopic polypectomies, and same-day CTC. MAIN OUTCOME MEASUREMENTS: Our main outcome measurements included perforation rate with long-term follow-up. RESULTS: A total of 3% of patients undergoing colonoscopy from January 2008 to December 2012 had same-day CTC following incomplete OC, and 72 polypectomies were performed in 34 (or 17%) of these patients. Incomplete colonoscopies were due to colon tortuosity and looping (25), severe angulations (five), colon mass (two), colon stenosis (one), bradycardia (one). Fifty-three percent of the OCs were screening for colon neoplasia, 29% diagnostic and 18% were surveillance of colon polyps. Most polyps were <= 5 mm, and found in the left colon. There were no reported complications or perforations associated with same-day CTCs during short and long-term follow-up. LIMITATIONS: Limitations of our analysis included retrospective single-center design, small number of patients for the occurrence, referral to same-day CTC was not standardized, inability to establish safety of CTC for specific scenarios such as after complex polypectomies, strictures, or advanced IBD. CONCLUSIONS: Radiologists' apprehension to perform a CTC the same day as an incomplete colonoscopy following polypectomies because of perceived risk of perforation may be unfounded. More data are needed to determine the safety of same-day CTC in patients with high-risk findings during colonoscopy such as a stricture, severe IBD, and after complex polypectomies. PMID- 26279845 TI - Screening for hepatitis C in average and high-risk populations of Qatar using rapid point-of-care testing. AB - BACKGROUND: Screening for hepatitis C has been found to be beneficial in high risk individuals and 'baby boomers'. OBJECTIVE: Our aim was to screen for hepatitis C in average and high-risk individuals and compare the disease characteristics and response to treatment among the screened group (SG) and non screened group (NSG). METHOD: Community-based screening for hepatitis C was done in the average and high-risk populations of Qatar. Screening was done using rapid point-of-care testing. All patients with stage 1 fibrosis on liver biopsy were treated with pegylated interferon and ribavirin. RESULTS: In total, 13,704 people were screened and 272 (2%, 95% CI (1.8-2.2%) had positive antibodies to hepatitis C. During the same period, 237 non-screened patients (NSG) with hepatitis C were referred for treatment. Alanine and aspartate aminotransferases (ALT, AST) and overall fibrosis were significantly lower in the SG as compared with the NSG (p = 0.04, 0.04 and 0.01, respectively). The response to treatment was similar in the SG as compared with the NSG (sustained viral response 61.7 % versus 69.1%, p = 0.55). Average-risk patients had significantly lower ALT levels (p = 0.04) but had similar response to treatment as the high-risk individuals (sustained viral response 63.2 % versus 61%, p = 0.87). CONCLUSION: Screening detects hepatitis C with lesser fibrosis but does not result in better response to pegylated interferon and ribavirin as compared with non-screened patients. PMID- 26279846 TI - Management of Crohn's disease - are guidelines transferred to clinical practice? AB - BACKGROUND: Management of Crohn's disease (CD) is a clinical challenge. In terms of an evidence-based approach, clinical guidelines help to deal with this challenge. However, little is known about guideline adherence concerning the management of CD in Germany. OBJECTIVE: To survey German gastroenterologists with regards to their guideline adherence in daily clinical care. METHOD: A web-based national survey was conducted among German gastroenterologists. RESULTS: A total of 175 inflammatory bowel disease (IBD) practitioners responded to the survey. Overall, in the different clinical situations covered in the questionnaire guideline adherence is good. However, the 5-aminosalicylic acid (5-ASA) prescribing habits represent a striking exception. About 10-36% use 5-ASA as mono therapy in CD, depending on the clinical scenario. Predominantly it is used in mild CD and in colonic involvement. To maintain a surgically achieved remission, therapeutic decisions broadly rely on individual approaches with azathioprine and 5-ASA being used by about 30% of the respondents. Cessation of smoking as a "therapeutic" strategy of maintenance therapy is used by only half of the surveyed physicians. CONCLUSION: Amongst German IBD practitioners, the guideline adherence is good overall. Reflecting ongoing uncertainty about the efficacy of mesalazine, its use in Crohn's disease is still heterogeneous. PMID- 26279847 TI - Are the definitions for chronic diarrhoea adequate? Evaluation of two different definitions in patients with chronic diarrhoea. AB - BACKGROUND: The classical definition of chronic diarrhoea is >=3 defecations/day, with a stool weight of more than 200 g and duration of >=4 weeks. However, with this definition many patients with substantial symptoms and pathology will be excluded from further investigations. As a consequence other definitions have been proposed, mainly based on evaluation of the stool form. OBJECTIVE: To evaluate the accuracy of the classic criteria for diarrhoea in comparison with a definition based on stool consistency, using the Bristol Stool Form Scale. METHODS: All patients were investigated with laboratory tests, upper and lower gastrointestinal endoscopy with biopsies, and SeHCAT test. They were asked to complete a diary recording stool frequency and consistency during a week, as well as other gastrointestinal symptoms (pain, bloating and gas). RESULTS: One hundred and thirty-nine subjects were eligible for analysis. Ninety-one had an organic cause of diarrhoea. Fifty-three patients had >=3 loose stools/day, whereas 86 reported <3 stools/day. Ninety had a median stool consistency that was mushy or loose and 49 had harder stools. A higher proportion of subjects with an organic cause of their diarrhoea compared with subjects with a functional bowel disorder had >=3 loose stools/day, 43/91 (47%) vs. 10/48 (21%) (p < 0.01). Similarly, more subjects with an organic cause of their diarrhoea versus patients with a functional bowel disorder had a median stool consistency that was mushy or watery, 73/91 (80%) vs. 17/48 (35%), p < 0.0001. When diarrhoea was defined according to stool form, more patients were classified correctly as having a functional disorder or organic disorder, compared with the classical definition (p < 0.05). CONCLUSION: Loose stools defined according to the Bristol Stool Form scale seem to be the best predictor of having an organic cause of the diarrhoea. PMID- 26279848 TI - Risk factors for polyp retrieval failure in colonoscopy. AB - INTRODUCTION: Colonoscopy is able to diagnose, resect and retrieve colonic polyps. Although retrieval of resected polyps is still globally advised, it is not always successful. We aimed to define the risk factors for polyp retrieval failure in colonoscopy. METHODS: A single-center, retrospective study assessed 3507 consecutive and non-urgent colonoscopies, performed between September 2011 and December 2012. Colonoscopies were included in our analysis if the diagnosis of at least one polyp was established, and one or more snare polypectomies were performed. Demographic and technical data were collected according to the patient's endoscopy report. RESULTS: A total of 1109 polyps were analyzed, corresponding to 496 colonoscopies from 483 different patients. We found that 53 (4.8%) of the resected polyps were not retrieved. In a univariate analysis, the factors associated with polyp retrieval failure were: age, polyp size, resection technique, bowel preparation, location and the presence of a previous colorectal surgery (p < 0.05). In the multivariate analysis, a previous colorectal surgery, resection by cold snare, location in the right colon, inadequate bowel preparation and a polyp size up to 5 mm were independently associated with higher polyp retrieval failure (p < 0.05). DISCUSSION: Different and well-defined factors were associated with polyp retrieval failure. Because bowel preparation was the only modifiable factor identified, a special focus should be given to this topic. PMID- 26279849 TI - Aseptic non-touch technique and catheter-related bloodstream infection in children receiving parenteral nutrition at home. AB - OBJECTIVES: Parenteral nutrition (PN) at home is an acceptable form of delivering long-term PN for children with intestinal failure. Catheter-related bloodstream infection (CRBSI) is one of the serious complications of long-term PN and can lead to increasing morbidity and mortality. Using aseptic non-touch technique (ANTT) was proven to decrease the incidence of CRBSI in hospital patients. In this study we aimed to review the incidence of CRBSI in children receiving PN at home in our institution using the ANTT and a simplified training programme for parents and carers. METHODS: We retrospectively collected clinical and microbiological data on all children with intestinal failure (IF) who were on treatment with PN at home under our specialist IF rehabilitation service between November 2012 and November 2013. RESULTS: Thirty-five children were included, 16 of whom did not have any infection recorded during the study period. The overall CRBSI rate was 1.3 infections per 1000 line-days, with Staphylococcus being the commonest organism. Twenty-one children did not require catheter change and the overall catheter changes were 1.8 per 1000 line-days. CONCLUSION: In this article, we report a low incidence of CRBSI in a single institution by using the principle of ANTT for accessing central venous catheters combined with a simplified, nurse-led, two-week standardised training programme for parents of children going home on PN. PMID- 26279850 TI - Automated telemetry reveals age specific differences in flight duration and speed are driven by wind conditions in a migratory songbird. AB - BACKGROUND: Given that winds encountered on migration could theoretically double or half the energy expenditure of aerial migrants, there should be strong selection on behaviour in relation to wind conditions aloft. However, evidence suggests that juvenile songbirds are less choosy about wind conditions at departure relative to adults, potentially increasing energy expenditure during flight. To date, there has yet to be a direct comparison of flight efficiency between free-living adult and juvenile songbirds during migration in relation to wind conditions aloft, likely because of the challenges of following known aged individual songbirds during flight. We used an automated digital telemetry array to compare the flight efficiency of adult and juvenile Savannah sparrows (Passerculus sandwichensis) as they flew nearly 100 km during two successive stages of their fall migration; a departure flight from their breeding grounds out over the ocean and then a migratory flight along a coast. Using a multilevel path modelling framework, we evaluated the effects of age, flight stage, tailwind component, and crosswind component on flight duration and groundspeed. RESULTS: We found that juveniles departed under wind conditions that were less supportive relative to adults and that this resulted in juveniles taking 1.4 times longer to complete the same flight trajectories as adults. We did not find an effect of age on flight duration or groundspeed after controlling for wind conditions aloft, suggesting that both age groups were flying at similar airspeeds. We also found that groundspeeds were 1.7 times faster along the coast than over the ocean given more favourable tailwinds along the coast and because birds appeared to be climbing in altitude over the ocean, diverting some energy from horizontal to vertical movement. CONCLUSIONS: Our results provide the first evidence that adult songbirds have considerably more efficient migratory flights than juveniles, and that this efficiency is driven by the selection of more supportive tailwind conditions aloft. We suggest that the tendency for juveniles to be less choosy about wind conditions at departure relative to adults could be adaptive if the benefits of having a more flexible departure schedule exceed the time and energy savings realized during flight with more supportive winds. PMID- 26279851 TI - A case of thyroid storm complicated by acute hepatitis due to propylthiouracil treatment. AB - A 57-year-old female presented 17 days after treatment with radioactive iodine (RAI) for difficult-to-control hyperthyroidism. She was febrile, had a sinus tachycardia, and was clinically thyrotoxic. Her thyroid function tests showed a suppressed TSH <0.02 mU/l, with free thyroxine (FT4) >75 pmol/l and total triiodothyronine (TT3) 6.0 nmol/l. She was diagnosed with thyroid storm and was managed with i.v. fluids, propylthiouracil (PTU) 200 mg four times a day, prednisolone 30 mg once daily and propanolol 10 mg three times a day. She gradually improved over 2 weeks and was discharged home on PTU with beta blockade. On clinic review 10 days later, it was noted that, although she was starting to feel better, she had grossly abnormal liver function (alanine transaminase (ALT) 852 U/l, bilirubin 46 MUmol/l, alkaline phosphatase (ALP) 303 U/l, international normalized ratio (INR) 0.9, platelets 195*10(9)/l). She was still mildly thyrotoxic (TSH <0.02 mU/l, FT4 31 pmol/l, TT3 1.3 nmol/l). She was diagnosed with acute hepatitis secondary to treatment with PTU. Ultrasound showed mild hepatic steatosis. PTU was stopped and she was managed with fluids and prednisolone 60 mg once daily and continued beta blockade. Her liver function gradually improved over 10 days (bilirubin 9 MUmol/l, ALT 164 U/l, ALP 195 U/l, INR 0.9, platelets 323*10(9)/l) with conservative management and had normalised by clinic review 3 weeks later. This case highlights the potentially fatal, but rare, complications associated with both RAI and PTU, namely, thyroid storm and acute hepatitis respectively. LEARNING POINTS: Thyroid storm is an important, albeit rare, endocrinological emergency.Thyroid storm following RAI treatment is extremely rare.Management is with i.v. fluids, beta blockade, anti-thyroid drugs and steroids.High dose glucocorticoid steroids can block the peripheral conversion of T4 to active T3.Liver dysfunction, acute hepatitis and potential hepatic failure are significant adverse drug reactions known to occur with PTU treatment. Supervising clinicians should be vigilant for evidence of this developing and intervene accordingly.Clinicians need to be aware of possible interactions between regular paracetamol use and PTU in predisposing to liver impairment. PMID- 26279852 TI - Pituitary hyperplasia: an uncommon presentation of a common disease. AB - A 21-year-old woman presented with amenorrhea, bilateral galactorrhea and fatigue. Visual acuity and visual fields were normal. Laboratory examination demonstrated hyperprolactinemia. Magnetic resonance imaging (MRI) of the pituitary showed a 19*17*12-mm sellar mass with supra- and parasellar extension, causing compression of the pituitary stalk and optic chiasm. Further examinations confirmed mild hyperprolactinemia, strongly elevated TSH (>500 mU/l), low free thyroxine (FT4), hypogonadotropic hypogonadism and secondary adrenal insufficiency. Hydrocortisone and l-T4 replacement therapy was started. Three months later, the galactorrhea had disappeared, thyroid function was normalized and MRI revealed regression of the pituitary enlargement, confirming the diagnosis of pituitary hyperplasia (PH) due to primary hypothyroidism. Subsequently, the menstrual cycle returned and the hypocortisolism normalized. This case demonstrates that severe primary hypothyroidism may have an unusual presentation and should be considered in the differential diagnosis of pituitary enlargement associated with moderate hyperprolactinemia. LEARNING POINTS: One should always try to find one etiology as the common cause of all the clinical findings in a pathologic process.Amenorrhea, galactorrhea and fatigue may be the only presenting clinical manifestations of primary hypothyroidism.Not every patient with galactorrhea, hyperprolactinemia and a pituitary mass has a prolactinoma.Primary hypothyroidism should always be considered in the differential diagnosis of hyperprolactinemia associated with pituitary enlargement and pituitary hormone(s) deficiency(ies).When PH due to primary hypothyroidism is suspected, thyroid hormone replacement should be started and only regression of pituitary enlargement on MRI follow-up can confirm the diagnosis.Examination of thyroid function in patients with a pituitary mass may avoid unnecessary surgery. PMID- 26279853 TI - Physician smoking cessation counseling and adherence to a clinical practice guideline. AB - OBJECTIVE: The U.S. Public Health Service Clinical Practice Guideline recommends that physicians provide tobacco cessation interventions to their patients at every visit. While many studies have examined the extent to which physicians implement the guideline's "5 A's", few studies have examined the extent to which physicians implement the guideline's "5 R's" which are to be used in a Motivational Interviewing (MI) consistent style with smokers not ready to quit. This study examined the extent to which physicians in usual practice and without specific training administered the 5 R's including the use of an MI style. METHODS: Thirty-eight physicians were audio recorded during their routine clinical practice conversations with smokers.Recordings were coded by independent raters on the implementation of each of the 5 A's, 5 R's and MI counseling style. RESULTS: Results revealed that for patients not ready to quit smoking, physicians most frequently discussed the patient's personal relevance for quitting and the risks of smoking. Roadblocks and rewards were discussed relatively infrequently. MI skill code analyses revealed that physicians, on average, had moderate scores for acceptance and autonomy support, a low to moderate score for collaboration and low scores for empathy and evocation. CONCLUSION: Results suggest that for the Clinical Guideline to be implemented appropriately physicians will need specialized training or will need to be able to refer patients to counselors with the necessary expertise. Counseling efforts could increase providers' willingness to implement guideline recommendations and therefore to enhance the person centeredness of clinical care. PMID- 26279854 TI - Crystal structure of (E)-N'-(5-bromo-2-hy-droxy-benzyl-idene)nicotinohydrazide monohydrate. AB - In the title compound, C13H10BrN3O2.H2O, the conformation about the azomethine double bond is E. The mol-ecule exists in the amido form with a C=O bond length of 1.229 (2) A. There is an intra-molecular O-H?N hydrogen bond forming an S(6) ring motif. The whole mol-ecule is almost planar, with an r.m.s. deviation of 0.021 A for all non-H atoms, and the dihedral angle between the planes of the pyridine and benzene rings is 0.74 (12) degrees . In the crystal, the water mol ecule of crystallization links the organic mol-ecules via Ow-H?O, Ow-H?N and N H?Ow hydrogen bonds and short C-H?Ow contacts, forming sheets lying parallel to (100). Within the sheets there is a weak pi-pi inter-action involving the pyridine and benzene rings [centroid-to-centroid distance = 3.8473 (15) A]. The sheets are linked via C-H?Br inter-actions, forming a three-dimensional network. PMID- 26279855 TI - Crystal structure of the co-crystalline adduct 1,3,6,8-tetra-aza-tri-cyclo [4.4.1.1(3,8)]dodecane (TATD)-4-chloro-3,5-di-methyl-phenol (1/1). AB - In the crystal of the title co-crystalline adduct, C8H16N4.C8H9ClO, (I), prepared by solid-state reaction, the mol-ecules are linked by inter-molecular O-H?N hydrogen bonds, forming a D motif. The aza-adamantane structure in (I) is slightly distorted, with N-CH2-CH2-N torsion angles of 10.4 (3) and -9.0 (3) degrees . These values differ slightly from the corresponding torsion angles in the free aminal cage (0.0 degrees ) and in related co-crystalline adducts, which are not far from a planar geometry and consistent with a D 2d mol-ecular symmetry in the tetra-aza-tri-cyclo structure. The structures also differ in that there is a slight elongation of the N-C bond lengths about the N atom that accepts the hydrogen bond in (I) compared with the other N-C bond lengths. In the crystal, the two mol-ecules are not only linked by a classical O-H?N hydrogen bond but are further connected by weak C-H?pi inter-actions, forming a two-dimensional supra molecular network parallel to the bc plane. PMID- 26279856 TI - Crystal structure of methyl (S)-2-{(R)-4-[(tert-but-oxy-carbon-yl)amino]-3-oxo 1,2-thia-zolidin-2-yl}-3-methyl-butano-ate: a chemical model for oxidized protein tyrosine phosphatase 1B (PTP1B). AB - The asymmetric unit of the title compound, C14H24N2O5S, contains two independent mol-ecules (A and B). In each mol-ecule, the iso-thia-zolidin-3-one ring adopts an envelope conformation with the methyl-ene C atom as the flap. In the crystal, the A mol-ecules are linked to one another by N-H?O hydrogen bonds, forming columns along [010]. The B mol-ecules are also linked to one another by N-H?O hydrogen bonds, forming columns along the same direction, i.e. [010]. Within the individual columns, there are also C-H?S and C-H?O hydrogen bonds present. The columns of A and B mol-ecules are linked by C-H?O hydrogen bonds, forming sheets parallel to (10-1). The absolute structure was determined by resonant scattering [Flack parameter = 0.00 (3)]. PMID- 26279857 TI - Crystal structures of 4-chloro-phenyl N-(3,5-di-nitro-phen-yl)carbamate and phenyl N-(3,5-di-nitro-phen-yl)carbamate. AB - The title compounds, C13H8ClN3O6, (I), and C13H9N3O6, (II), differ in the orientation of the two aromatic rings. In (I), they are essentially coplanar, making a dihedral angle of 8.2 (1) degrees , while in (II), they are inclined to one another by 76.2 (1) degrees . The two nitro groups are essentially coplanar with the attached benzene rings, as indicated by the dihedral angles of 1.4 (2) and 2.3 (2) degrees in (I), and 4.96 (18) and 5.4 (2) degrees in (II). The carbamate group is twisted slightly from the attached benzene ring, with a C-N-C O torsion angle of -170.17 (15) degrees for (I) and 168.91 (13) degrees for (II). In the crystals of of both compounds, mol-ecules are linked via N-H?O hydrogen bonds, forming chains propagating along [010]. In (I), C-H?O hydrogen bonds also link mol-ecules within the chains. The crystal packing in (I) also features a very weak pi-pi inter-action [centroid-centroid distance = 3.7519 (9) A]. PMID- 26279858 TI - Crystal structure of tetra-methyl-tetra-thia-fulvalenium (1S)-camphor-10 sulfonate dihydrate. AB - Electro-oxidation of tetra-methyl-tetra-thia-fulvalene (TMTTF) in the presence of the chiral anion (1S)-camphor-10-sulfonate (S-camphSO3 (-)) in tetra-hydro furan/water medium afforded a 1/1 salt formulated as TMTTF.S-camphSO3.2H2O or 2 (4,5-dimethyl-1,3-di-thiol-2-yl-idene)-4,5-dimethyl-1,3-di-thiole radical ion (1+) [(1S)-7,7-dimethyl-2-oxobi-cyclo-[2.2.1]heptan-1-yl]methane-sulfonate dihydrate, C10H12S4 (+).C10H15O4S(-).2H2O. In this salt, two independent TMTTF units are present but, in both cases, the observed bond lengths and especially the central C=C distance [1.392 (6) and 1.378 (6) A] are in agreement with a complete oxidation of TMTTF which is thus present as TMTTF (.) (+) radical cations. These cations form one-dimensional stacks in which they are associated two by two, forming dimers with short [3.472 (1) to 3.554 (2) A] S?S contacts. The two S-camphSO3 anions present also form stacks and are connected with each other via the water mol-ecules with many O-H?O hydrogen bonds ranging from 1.86 (3) to 2.15 (4) A; the O-H?O hydrogen-bonding network can be described as being constituted of C 2 (2)(6) chains bearing R 3 (3)(11) lateral rings. On the other hand, the columns of cations and anions are connected through C-H?O hydrogen bonds, forming a system expanding in three directions; finally, the result is a three-dimensional network of O-H?O and C-H?O hydrogen bonds. PMID- 26279859 TI - Different hydrogen-bonded chains in the crystal structures of three alkyl N-[(E) 1-(2-benzyl-idene-1-methyl-hydrazin-yl)-3-hy-droxy-1-oxopropan-2-yl]carbamates. AB - The crystal structures of three methyl-ated hydrazine carbamate derivatives prepared by multi-step syntheses from l-serine are presented, namely benzyl N {(E)-1-[2-(4-cyanobenzylidene)-1-methylhydrazinyl]-3-hydroxy-1-oxopro-pan-2 yl}carbamate, C20H20N4O4, tert-butyl N-{(E)-1-[2-(4-cyanobenzylidene)-1 methylhydrazinyl]-3-hydroxy-1-oxopropan-2-yl}carbamate, C17H22N4O4, and tert butyl N-[(E)-1-(2-benzylidene-1-methylhydrazinyl)-3-hydroxy-1-oxopro-pan-2 yl]carbamate, C16H23N3O4. One of them shows that an unexpected racemization has occurred during the mild-condition methyl-ation reaction. In each crystal structure, the mol-ecules are linked into chains by O-H?O hydrogen bonds, but with significant differences between them. PMID- 26279860 TI - Crystal structure of N,N-dimethyl-2-[(4-methyl-benz-yl)sulfon-yl]ethanamine. AB - In the crystal, the title compound, C12H19NO2S, has a disordered structure with two equally populated conformations of the amine fragment. A pair of weak C-H?O inter-molecular inter-actions between the CH2 and SO2 groups gives a one dimensional supra-molecular structure that propagates through translation along the a-axis direction. PMID- 26279861 TI - Crystal structure of Sc1.91In1.39Mo15Se19, containing Mo6 and Mo9 clusters. AB - The structure of scandium indium penta-deca-molybdenum nona-deca-selenide, Sc1.91In1.39Mo15Se19, is isotypic with In2.9Mo15Se19 [Gruttner et al. (1979 ?). Acta Cryst. B35, 285-292]. It is characterized by two cluster units Mo6Se (i) 8Se (a) 6 and Mo9Se (i) 11Se (a) 6 (where i represents inner and a apical atoms) that are present in a 1:1 ratio. The cluster units are centered at Wyckoff positions 2b and 2c and have point-group symmetry -3 and -6, respectively. The clusters are inter-connected through additional Mo-Se bonds. Sc-Se and In-Se bonds complete the structural set-up. In the title compound, the Sc(3+) cations replace the trivalent indium atoms present in In2.9Mo15Se19, and a deficiency is observed at the monovalent indium site. One Mo, one Se and the Sc atom are situated on mirror planes, whereas two other Se atoms and the In atom are situated on threefold rotation axes. PMID- 26279862 TI - Crystal structure of 3-(thio-phen-2-yl)-5-p-tolyl-4,5-di-hydro-1H-pyrazole-1 carbo-thio-amide. AB - In the title compound, C15H15N3S2, the central pyrazole ring adopts a twisted conformation on the -CH-CH2- bond. Its mean plane makes dihedral angles of 7.19 (12) and 71.13 (11) degrees with those of the thio-phene and toluene rings, respectively. The carbothi-amide group [C(=S)-N] is inclined to the pyrazole ring mean plane by 16.8 (2) degrees . In the crystal, mol-ecules are linked by N-H?S hydrogen bonds, forming chains propagating along [010]. Within the chains, there are N-H?pi inter-actions present. Between the chains there are weak parallel slipped pi-pi inter-actions involving inversion-related thio-phene and pyrazole rings [inter-centroid distance = 3.7516 (14) A; inter-planar distance = 3.5987 (10) A; slippage = 1.06 A]. PMID- 26279863 TI - Crystal structures of two 6-(2-hy-droxy-benzo-yl)-5H-thia-zolo[3,2-a]pyrimidin-5 ones. AB - The title compounds, 6-(2-hy-droxy-benz-yl)-5H-thia-zolo[3,2-a]pyrimidin-5-one, C13H8N2O3S, (1), and 6-(2-hy-droxy-benz-yl)-3-methyl-5H-thia-zolo[3,2-a]pyrimidin 5-one, C14H10N2O3S, (2), were synthesized when a chromone-3-carb-oxy-lic acid, activated with (benzotriazol-1-yl-oxy)tripyrrolidinyl-phospho-nium hexa-fluorido phosphate (PyBOP), was reacted with a primary heteromamine. Instead of the expected amidation, the unusual title thia-zolo-pyrimidine-5-one derivatives were obtained serendipitously and a mechanism of formation is proposed. Both compounds present an intra-molecular O-H?O hydrogen bond, which generates an S(6) ring. The dihedral angles between the heterocyclic moiety and the 2-hydroxybenzoyl ring are 55.22 (5) and 46.83 (6) degrees for (1) and (2), respectively. In the crystals, the mol-ecules are linked by weak C-H?O hydrogen bonds and pi-pi stacking inter actions. PMID- 26279864 TI - Crystal structure of a mono-bridged calix[4]arene. AB - The title compound, 5(2)-[(5-bromo-pent-yl)-oxy]-1(2),1(14),3(5),5(5)-tetra-tert butyl-1(7),1(8),1(9),1(10)-tetra-hydro-1(6) H,1(16) H-1(4,12) dibenzo[b,e][1,7]dioxa-cyclo-dodecina-3,5(1,3)-dibenzena-cyclo-hexa-phan-3(2)-ol, C54H73BrO4, was synthesized from the reaction of tert-butyl-calix[4]arene with 1,5-di-bromo-pentane using K2CO3 in CH3CN. The structure consists of a calixarene unit with a five-carbon bridge connecting two proximal phenolic O atoms, and with a bromo-pent-oxy chain on one of the remaining phenolic O atoms. The calixarene unit was found to have a flattened cone conformation with no solvent (or other guest) mol-ecule observed in the cavity. Two of the opposite phenyl rings lean outwards with fold angles of 136.2 (1) and 133.0 (1) degrees between the rings and the plane of the bridging methyl-ene C atoms, while the other two opposite rings form fold angles of 83.27 (9) and 105.46 (9) degrees . There is considerable disorder in this mol-ecule. One of the tert-butyl groups is disordered over two conformations with occupancies of 0.527 (5) and 0.473 (5). The bromo-pent-oxy chain is disordered over three configurations with occupancies of 0.418, 0.332 and 0.250. The five-carbon bridge connecting two proximal phenolic O atoms is disordered over two conformations with occupancies of 0.537 (7) and 0.463 (7). PMID- 26279865 TI - Crystal structure of high-spin tetra-aqua-bis-(2-chloro-pyrazine-kappaN (4))iron(II) bis-(4-methyl-benzene-sulfonate). AB - The title salt, [Fe(II)(C4H3ClN2)2(H2O)4](C7H7O3S)2, contains a complex cation with point group symmetry 2/m. The high-spin Fe(II) cation is hexa-coordinated by four symmetry-related water and two N-bound 2-chloro-pyrazine mol-ecules in a trans arrangement, forming a distorted FeN2O4 octa-hedron. The three-dimensional supra-molecular structure is supported by inter-molecular O-H?O hydrogen bonds between the complex cations and tosyl-ate anions, and additional pi-pi inter actions between benzene and pyrazine rings. The methyl H atoms of the tosyl-ate anion are equally disordered over two positions. PMID- 26279867 TI - Crystal structure of 1,10-phenanthrolinium 3-hy-droxy-2,4,6-tri-nitro-phenolate. AB - In the title molecular salt, C12H9N2 (+).C6H2N3O8 (-), the cation and anion are connected by an N-H?O hydrogen bond. In the anion, an intra-molecular O-H?O hydrogen bond with an S(6) ring motif is observed. The planes of two of the nitro groups are approximately parallel to the plane of the benzene ring, making dihedral angles of 3.9 (2) and 15.3 (2) degrees , while the third nitro group is almost perpendicular to the benzene ring, with a dihedral angle of 78.6 (3) degrees . In the crystal, cation-anion pairs related by an n-glide plane are connected by C-H?O hydrogen bonds, forming a chain structure along [101]. Sensitivity tests and thermal testing indicate that the title salt is an insensitive high-energy-density material (IHEDM). PMID- 26279870 TI - Crystal structure of (E)-N-{2-[2-(2-chloro-benzyl-idene)hydrazin-1-yl]-2-oxoeth yl}-4-methyl-benzamide monohydrate. AB - The title compound, C17H16ClN3O2.H2O, an acyl-hydrazone derivative, contains a glycine moiety and two substituted benzene rings on either end of the chain. It crystallized as a monohydrate. The mol-ecules adopt an E conformation with respect to the C=N double bond, as indicated by the N-N=C-C torsion angle of 179.38 (14) degrees . The mol-ecule is twisted in such a way that the almost planar Car-C(=O)-N(H)-C(H2) and C(H2)-C(=O)N(H)-N=C-Car [r.m.s deviations = 0.009 and 0.025 A, respectively] segments are inclined to on another by 77.36 (8) degrees , while the benzene rings are normal to one another, making a dihedral angle of 89.69 (9) degrees . In the crystal, the water mol-ecule links three mol ecules through two O-H?O and one N-H?O hydrogen bonds. The mol-ecules are linked via pairs of N-H?O hydrogen bonds, forming inversion dimers with an R 2 (2)(14) ring motif. The dimers are linked by O-H?O hydrogen bonds, involving two mol ecules of water, forming chains along [100], enclosing R 2 (2)(14) and R 2 (2)(18) ring motifs. The chains are linked through C-H?O inter-actions, forming sheets parallel to (010). Within the sheets, there are C-H?pi and parallel slipped pi-pi stacking inter-actions present [inter-centroid distance = 3.6458 (12) A]. PMID- 26279868 TI - Double salt crystal structure of nona-sodium dihydrogen nona-vanadoplatinate(IV) tri-hydrogen nona-vanadoplatinate(IV) tetra-contahydrate: stepwise-protonated nona-vanadoplatinate(IV). AB - Nonavanadoplatinate [Pt(IV)V9O28](7-), which is the first heteropolyoxovanadate in the deca-vanadate framework, [V10O28](6-), has been investigated crystallographically. The title compound, Na9[H2Pt(IV)V9O28][H3Pt(IV)V9O28].40H2O, was obtained by a hydro-thermal reaction at pH = 2. This compound contains two different protonated heteropolyoxovanadates, [H2Pt(IV)V9O28](5-) [polyanion (A)] and [H3Pt(IV)V9O28](7 ) [polyanion (B)]. The locations of the H atoms on the protonated O atoms were observed in difference Fourier maps and confirmed by the inter-polyanion hydrogen bonds, bond-length elongation and bond-valence-sum (VBS) analysis. The two (Pt and V)-bound MU2-O atoms are protonated in both polyanions. The position of the third protonated O atom in polyanion (B) is an inter-esting feature of the structure, being located on one (V2)-bound MU2-O atom. The discrete heteropolyanions form a dimer, {H5[PtV9O28]2}(9-), through five inter-polyanion hydrogen bonds. Additional O-H?O hydrogen bonds and interactions between Na(+) cations and water molecules as well as terminal O atoms of one of the polyanions consolidate the crystal packing. PMID- 26279871 TI - Crystal structures of deuterated sodium molybdate dihydrate and sodium tungstate dihydrate from time-of-flight neutron powder diffraction. AB - Time-of-flight neutron powder diffraction data have been measured from ~90 mol% deuterated isotopologues of Na2MoO4.2H2O and Na2WO4.2H2O at 295 K to a resolution of sin (theta)/lambda = 0.77 A(-1). The use of neutrons has allowed refinement of structural parameters with a precision that varies by a factor of two from the heaviest to the lightest atoms; this contrasts with the X-ray based refinements where precision may be > 20* poorer for O atoms in the presence of atoms such as Mo and W. The accuracy and precision of inter-atomic distances and angles are in excellent agreement with recent X-ray single-crystal structure refinements whilst also completing our view of the hydrogen-bond geometry to the same degree of statistical certainty. The two structures are isotypic, space-group Pbca, with all atoms occupying general positions, being comprised of edge- and corner sharing NaO5 and NaO6 polyhedra that form layers parallel with (010) inter-leaved with planes of XO4 (X = Mo, W) tetra-hedra that are linked by chains of water mol ecules along [100] and [001]. The complete structure is identical with the previously described molybdate [Capitelli et al. (2006 ?). Asian J. Chem. 18, 2856-2860] but shows that the purported three-centred inter-action involving one of the water mol-ecules in the tungstate [Farrugia (2007 ?). Acta Cryst. E63, i142] is in fact an ordinary two-centred 'linear' hydrogen bond. PMID- 26279866 TI - Crystal structure of trans-(1,8-dibutyl-1,3,6,8,10,13-hexa-aza-cyclo-tetra-decane kappa(4) N (3),N (6),N (10),N (13))bis-(thio-cyanato-kappaN)nickel(II) from synchrotron data. AB - The crystal structure of the title compound, [Ni(NCS)2(C16H38N6)], has been determined from synchrotron data. The asymmetric unit consists of two halves of the complex mol-ecules which have their Ni(II) atoms located on inversion centres. The Ni(II) ions show a tetra-gonally distorted octa-hedral coordination geometry, with four secondary amine N atoms of the aza-macrocyclic ligand in the equatorial plane and two N atoms of the thio-cyanate anions in the axial positions. The average equatorial Ni-N bond length [2.070 (5) A] is shorter than the average axial Ni-N bond length [2.107 (18) A]. Only half of the macrocyclic ligand N-H groups are involved in hydrogen bonding. The complex mol-ecules are connected via inter-molecular N-H?S hydrogen bonds into two symmetry-independent one-dimensional polymeric structures extending along the b-axis direction. One of the n-butyl substituents of the macrocycle exhibits conformational disorder with a refined occupancy ratio of 0.630:0.370. PMID- 26279872 TI - 'Pd20Sn13' revisited: crystal structure of Pd6.69Sn4.31. AB - The crystal structure of the title compound was previously reported with composition 'Pd20Sn13' [Sarah et al. (1981 ?). Z. Metallkd, 72, 517-520]. For the original structure model, as determined from powder X-ray data, atomic coordinates from the isostructural compound Ni13Ga3Ge6 were transferred. The present structure determination, resulting in a composition Pd6.69Sn4.31, is based on single crystal X-ray data and includes anisotropic displacement parameters for all atoms as well as standard uncertainties for the atomic coordinates, leading to higher precision and accuracy for the structure model. Single crystals of the title compound were obtained via a solid-state reaction route, starting from the elements. The crystal structure can be derived from the AlB2 type of structure after removing one eighth of the atoms at the boron positions and shifting adjacent atoms in the same layer in the direction of the voids. One atomic site is partially occupied by both elements with a Pd:Sn ratio of 0.38 (3):0.62 (3). One Sn and three Pd atoms are located on special positions with site symmetry 2. (Wyckoff letter 3a and 3b). PMID- 26279869 TI - Crystal structure of a mixed-ligand dinuclear Ba-Zn complex with 2-meth-oxy ethanol having tri-phenyl-acetate and chloride bridges. AB - The dinuclear barium-zinc complex, MU-chlorido-1:2kappa(2) Cl:Cl-chlorido 2kappaCl-bis-(2-meth-oxy-ethanol-1kappaO)bis-(2-meth-oxy-ethanol-1kappa(2) O,O')bis-(MU-tri-phenyl-acetato-1:2kappa(2) O:O')bariumzinc, [BaZn(C20H15O2)2Cl2(C3H8O2)4], has been synthesized by the reaction of barium tri phenyl-acetate, anhydrous zinc chloride and 2-meth-oxy-ethanol in the presence of toluene. The barium and zinc metal cations in the dinuclear complex are linked via one chloride anion and carboxyl-ate O atoms of the tri-phenyl-acetate ligands, giving a Ba?Zn separation of 3.9335 (11) A. The irregular nine coordinate BaO8Cl coordination centres comprise eight O-atom donors, six of them from 2-meth-oxy-ethanol ligands (four from two bidentate O,O'-chelate inter actions and two from monodentate inter-actions), two from bridging tri-phenyl acetate ligands and one from a bridging Cl donor. The distorted tetra-hedral coordination sphere of zinc comprises two O-atom donors from the tri-phenyl acetate ligands and two Cl donors (one bridging and one terminal). In the crystal, O-H?Cl, O-H?O and C-H?Cl inter-molecular inter-actions form a layered structure, lying parallel to (001). PMID- 26279873 TI - Crystal structure of metronidazolium tetra-chlorido-aurate(III). AB - Metronidazole (MET) [systematic names: 1-(2-hy-droxy-eth-yl)-2-methyl-5-nitro-1H imidazole and 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethanol] is a medication that is used to treat infections from a variety of anaerobic organisms. As with other imidazole derivatives, metronidazole is also susceptible to protonation. However, there are few reports of the structures of metronidazolium derivatives. In the title compound, (C6H10N3O3)[AuCl4] [systematic name: 1-(2-hy-droxy-eth-yl)-2 methyl-5-nitro-1H-imidazol-3-ium tetra-chlorido-aur-ate(III)], the asymmetric unit consists of a metronidazolium cation, [H(MET)](+), and a tetra-chlorido aurate(III) anion, [AuCl4](-), in which the Au(III) ion is in a slightly distorted square-planar coordination environment. In the cation, the nitro group is essentially coplanar with the imidazole ring, as indicated by an O N-C=C torsion angle of -0.2 (4) degrees , while the hy-droxy-ethyl group is in a coiled conformation, with an O(H)-C-C-N torsion angle of 62.3 (3) degrees . In the crystal, the anion and cation are linked by an inter-molecular O-H?Cl hydrogen bond. In addition, the N-H group of the metronidazolium ion serves as a hydrogen bond donor to the O atom of the hy-droxy-ethyl group of a symmetry-related mol ecule, leading to the formation of chains along [010]. PMID- 26279877 TI - Crystal structure of 2-(4-tert-butyl-phen-yl)-3-hydroxy-4H-chromen-4-one. AB - Yellow-green fluorescent crystals of the title compound, C19H18O3, were obtained by the reaction of hy-droxy-aceto-phenone and 4-tert-butyl-benzaldehyde with hydrogen peroxide as oxidant. The plane of the benzene ring is slightly twisted to the mean plane of the 4H-chromene-4-one moiety (r.m.s. deviation = 0.0191 A) by 10.53 (8) degrees . In the crystal, mol-ecules are linked by pairs of O-H?O hydrogen bonds, forming inversion dimers with an R 2 (2)(10) ring motif. The dimers are linked via C-H?pi inter-actions, forming sheets parallel to (10-1). PMID- 26279878 TI - Crystal structures of two triazola-dioxola-benzena-cyclo-nona-phanes. AB - In the title compounds, C25H29BrN5O7, (I) [systematic name: (Z)-1(5)-bromo 3(2),3(2)-dimethyl-2(1)-nitro 2(2),2(3),2(5),2(6),2(7),2(7a),3(3a),3(5),3(6),3(6a)-deca-hydro-2(1) H,6(1) H-4,9 dioxa-2(3,2)-pyrrolizina-6(4,1)-triazola-3(5,6)-furo[2,3-d][1,3]dioxola-1(1,2) benzena-cyclo-nona-phane], and C24H29N5O7S, (II) [systematic name: (Z)-3(2),3(2) dimethyl-2(7)-nitro-2(5),2(6),2(7),2(7a),3(3a),3(5),3(6),3(6a)-octa-hydro-2(1) H,2(3) H,6(1) H-4,9-dioxa-2(5,6)-pyrrolo-[1,2-c]thia-zola-6(4,1)-triazola-3(5,6) furo[2,3-d][1,3]dioxola-1(1,2)-benzena-cyclo-nona-phane], the triazole rings adopt almost planar conformations. In (I), the fused pyrrolidine rings adopt envelope conformations with the C atoms opposite the fused N-C bond as the flap in each ring, and their mean planes are inclined to one another by 52.8 (3) degrees . In (II), the pyrrolidine and thia-zole rings are both twisted on the fused N-C bond, and their mean planes are inclined to one another by 70.8 (2) degrees . In both (I) and (II), the furan ring adopts an envelope conformation with the adjacent C atom of the macrocycle as the flap. In the crystal of (I), mol-ecules are linked via C-H?N and C-H?O hydrogen bonds, forming sheets parallel to (10-1), while in (II), mol-ecules are linked via C-H?N and C-H?O hydrogen bonds, forming helical chains propagating along [010], which are linked via C-H?S hydrogen bonds, forming slabs parallel to (001). PMID- 26279876 TI - Crystal structure of ethyl 6-chloro-methyl-2-oxo-4-(2,3,4-tri-meth-oxy-phen-yl) 1,2,3,4-tetra-hydro-pyrimidine-5-carboxyl-ate. AB - In the title compound, C17H21ClN2O6, the di-hydro-pyrimidine ring adopts a flattened envelope conformation, with the sp (3)-hybridized C atom forming the flap. The dihedral angle between the least-squares planes of the benzene and di hydro-pyrimidine rings is 88.09 (6) degrees . An intra-molecular C-H?O hydrogen bond generates an S(6) ring. In the crystal, mol-ecules are linked via pairs of N H?O hydrogen bonds, forming inversion dimers with an R 2 (2)(8) ring motif, and the dimers are linked via further pairs of N-H?O hydrogen bonds, forming R 2 (2)(14) rings and chains of mol-ecules along [111]. Pairs of inversion-related chains are linked via weak C-H?pi inter-actions. PMID- 26279875 TI - Crystal structure of 4,4'-diethynylbiphen-yl. AB - The title compound, C16H10, crystallizes with four unique mol-ecules, designated 1-4, in the asymmetric unit of the monoclinic unit cell. None of the mol-ecules is planar, with the benzene rings of mol-ecules 1-4 inclined to one another at angles of 42.41 (4), 24.07 (6), 42.59 (4) and 46.88 (4) degrees , respectively. In the crystal, weak C-H?pi(ring) interactions, augmented by even weaker C C H?pi(alkyne) contacts, generate a three-dimensional network structure with inter linked columns of mol-ecules formed along the c-axis direction. PMID- 26279882 TI - Crystal structure of cis-2-(2-carb-oxy-cyclo-prop-yl)glycine (CCG-III) monohydrate. AB - The title compound, C6H9NO4.H2O [systematic name: (alphaR,1R,2S)-rel-alpha-amino 2-carb-oxy-cyclo-propane-acetic acid monohydrate], crystallizes with two organic mol-ecules and two water mol-ecules in the asymmetric unit. The space group is P21 and the organic mol-ecules are enanti-omers, thus this is an example of a 'false conglomerate' with two mol-ecules of opposite handedness in the asymmetric unit (r.m.s. overlay fit = 0.056 A for one mol-ecule and its inverted partner). Each mol-ecule exists as a zwitterion, with proton transfer from the amino acid carb-oxy-lic acid group to the amine group. In the crystal, the components are linked by N-H?O and O-H?O hydrogen bonds, generating (100) sheets. Conformationally restricted glutamate analogs are of inter-est due to their selective activation of different glutamate receptors, and the naturally occurring (+)-CCG-III is an inhibitor of glutamate uptake and the key geometrical parameters are discussed. PMID- 26279880 TI - Crystal structure of bis-(N-methyl-N-phenyl-amino)-tris-ulfane. AB - The title compound, C14H16N2S3, crystallized with two independent mol-ecules [(1 a ) and (1 b )] in the asymmetric unit. Both mol-ecules display a pseudo-trans conformation. The two consecutive S-S bond lengths of the tris-ulfane unit of mol ecule (1 a ) are 2.06 (3) and 2.08 (3) A, and 2.08 (3) and 2.07 (2) A for mol ecule (1 b ). Torsion angles about each of the two S-S bonds are 86.6 (2) and 87.0 (2) degrees for (1 a ), and -84.6 (2) and -85.9 (2) degrees for (1 b ). The core atoms, viz. the N-S-S-S-N moiety, of the two mol-ecules superimpose well if one is inverted on the other, but the phenyl groups do not. Thus, the two units are essentially conformational enanti-omers. In mol-ecule (1 a ), the two phenyl rings are inclined to one another by 86.7 (3) degrees , and in mol-ecule (1 b ), by 81.1 (3) degrees . In the crystal, mol-ecules are linked via C-H?pi inter-actions, forming sheets lying parallel to (010). PMID- 26279884 TI - Crystal structures of 4-chloro-pyridine-2-carbo-nitrile and 6-chloro-pyridine-2 carbo-nitrile exhibit different inter-molecular pi-stacking, C-H?Nnitrile and C H?Npyridine inter-actions. AB - The two title compounds are isomers of C6H3ClN2 containing a pyridine ring, a nitrile group, and a chloro substituent. The mol-ecules of each compound pack together in the solid state with offset face-to-face pi-stacking, and inter molecular C-H?Nnitrile and C-H?Npyridine inter-actions. 4-Chloro-pyridine-2-carbo nitrile, (I), exhibits pairwise centrosymmetric head-to-head C-H?Nnitrile and C H?Npyridine inter-actions, forming one-dimensional chains, which are pi-stacked in an offset face-to-face fashion. The inter-molecular packing of the isomeric 6 chloro-pyridine-2-carbo-nitrile, (II), which differs only in the position of the chloro substituent on the pyridine ring, exhibits head-to-tail C-H?Nnitrile and C H?Npyridine inter-actions, forming two-dimensional sheets which are pi-stacked in an offset face-to-face fashion. In contrast to (I), the offset face-to-face pi stacking in (II) is formed between mol-ecules with alternating orientations of the chloro and nitrile substituents. PMID- 26279879 TI - Crystal structure of a new homochiral one-dimensional zincophosphate containing l me-thio-nine. AB - catena-Poly[[(l-me-thio-nine-kappaO)zinc]-MU3-(hydrogen phosphato)-kappa(3) O:O':O''], [Zn{PO3(OH)}(C5H11NO2S)] n , a new one-dimensional homochiral zincophos-phate, was hydro-thermally synthesized using l-me-thio-nine as a structure-directing agent. The compound consists of a network of ZnO4 and (HO)PO3 tetra-hedra that form ladder-like chains of edge-fused Zn2P2O4 rings propagating parallel to [100]. The chains are decorated on each side by zwitterionic l-me thio-nine ligands, which inter-act with the inorganic framework via Zn-O coordination bonds. The structure displays inter-chain N-H?O and O-H?S hydrogen bonds. PMID- 26279881 TI - Crystal structure of 5-amino-4H-1,2,4-triazol-1-ium pyrazine-2-carboxyl-ate: an unexpected salt arising from the deca-rboxylation of both precursors. AB - Both the 3-amino-2H,4H-1,2,4-triazolium cation and the pyrazine-2-carboxyl-ate anion in the title salt, C2H5N4 (+).C5H3N2O2 (-), were formed by an unexpected deca-rboxylation reaction, from 5-amino-1H-1,2,4-triazole-3-carb-oxy-lic acid and pyrazine-2,3-di-carb-oxy-lic acid, respectively. The dihedral angle between the pyrazine ring (r.m.s. deviation = 0.008 A) and the carboxyl-ate group in the anion is 3.7 (3) degrees . The extended structure of the salt contains a supra molecular zigzag tape in which cations and anions are engaged in strong and highly directional N-H?N,O hydrogen bonds, forming R 2 (2)(8) and R 2 (2)(9) graph-set motifs. The packing between the tapes is mediated by pi-pi stacking inter-actions between the triazole and pyrazine rings. PMID- 26279885 TI - Crystal structure of 6-bromo-7-fluoro-4-oxo-4H-chromene-3-carbaldehyde. AB - In the title compound, C10H4BrFO3, a brominated and fluorinated 3-formyl-chromone derivative, all atoms are essentially coplanar (r.m.s. deviation of 0.025 A for the non-H atoms), with the largest deviation from the least-squares plane [0.050 (6) A] being for a benzene-ring C atom. In the crystal, mol-ecules are linked through stacking inter-actions [centroid-centroid distance between the benzene and pyran rings = 3.912 (4) A], C-H?O hydrogen bonds and short C?O contacts [2.865 (7) A]. Unsymmetrical halogen?halogen inter-actions between the bromine and fluorine atoms [Br?F = 3.116 (4) A, C-Br?F = 151.8 (2), C-F?Br = 154.1 (4) degrees ] are also formed, giving a meandering two-dimensional network propagating in the (041) plane. A comparison with related structures is made and the various types of weak inter-actions are ranked in importance. PMID- 26279883 TI - Crystal structure of ortho-rhom-bic {bis-[(pyridin-2-yl)meth-yl](3,5,5,5-tetra chloro-pent-yl)amine-kappa(3) N,N',N''}chlorido-copper(II) perchlorate. AB - In the title compound, [CuCl(C17H19Cl4N3)]ClO4, the Cu(II) ion adopts a distorted square-planar geometry defined by one chloride ligand and the three nitro-gen atoms from the bis-[(pyridin-2-yl)meth-yl](3,5,5,5-tetra-chloro-pent-yl)amine ligand. The perchlorate counter-ion is disordered over three sets of sites with refined occupancies 0.0634 (17), 0.221 (16) and 0.145 (7). In addition, the hetero-scorpionate arm of the bis-[(pyridin-2-yl)meth-yl](3,5,5,5-tetra-chloro pent-yl)amine ligand is disordered over two sets of sites with refined occupancies 0.839 (2) and 0.161 (2). In the crystal, weak Cu?Cl inter-actions between symmetry-related mol-ecules create a dimerization with a chloride occupying the apical position of the square-pyramidal geometry typical of many copper(II) chloride hetero-scorpionate complexes. PMID- 26279888 TI - Crystal structure of catena-poly[[tetra-aqua-magnesium]-MU-(di-hydrogen hypodiphosphato)-kappa(2) O:O']. AB - The crystal structure of the title compound, [Mg(H2P2O6)(H2O)4] n , is built up from (H2P2O6)(2-) anions bridging Mg(2+) cations into chains extending parallel to [011]. The Mg(2+) ion is located on an inversion centre and is octa-hedrally coordinated by the O atoms of two (H2P2O6)(2-) anions and four water mol-ecules. The centrosymmetric (H2P2O6)(2-) anion has a staggered conformation whereby the tetra-valent phospho-rus atom is surrounded tetra-hedrally by three O atoms and by one symmetry-related P atom. A three-dimensional O-H?O hydrogen-bonded network of medium strength involving the P-OH group of the anion and the water mol-ecules is present. PMID- 26279886 TI - Crystal structure of 4-hy-droxy-pyridin-1-ium 3,5-di-carb-oxy-benzoate. AB - The structure of the title salt, C5H6NO(+).C9H5O6 (-), (I), shows that 4-hy-droxy pyridine has abstracted an H atom from benzene-1,3,5-tri-carb-oxy-lic acid, yielding a pyridinium cation and carboxyl-ate anion. The two ions form an extensive three-dimensional hydrogen-bonded network throughout the crystal. The hydrogen bonds that comprise the core of the network are considered strong, with O-H?O and N-H?O donor-to-acceptor distances ranging from 2.533 (2) to 2.700 (2) A. Packing is further enhanced by pi-stacking of the cations and anions with like species [centroid-centroid distance = 3.6206 (13) A]. PMID- 26279887 TI - Crystal structure of 4-({5-[(E)-(3,5-di-fluoro-phen-yl)diazen-yl]-2-hy-droxy benzyl-idene}amino)-2,2,6,6-tetra-methyl-piperidin-1-ox-yl. AB - The asymmetric unit of the title compound, C22H25F2N4O2, contains two crystallographically independent mol-ecules. In one mol-ecule, the two benzene rings are oriented at a dihedral angle of 1.93 (10) degrees and in the other mol ecule the corresponding dihedral angle is 7.19 (9) degrees . The piperidine rings in the two mol-ecules adopt a similar distorted chair conformation, and both have pseudo-mirror planes passing through the N-O bonds. An intra-molecular O-H?N hydrogen bond between the hy-droxy group and the imine N atom is observed in both mol-ecules. In the crystal, weak C-H?O and C-H?F hydrogen bonds, enclosing R 2 (2)(6) ring motifs, and weak pi-pi stacking inter-actions link the mol-ecules into a three-dimensional supra-molecular network, with centroid-to-centroid distances between the nearly parallel phenyl and benzene rings of adjacent mol ecules of 3.975 (2) and 3.782 (2) A. PMID- 26279874 TI - Crystal structure of alluaudite-type NaMg3(HPO4)2(PO4). AB - The title compound, sodium trimagnesium bis-(hydrogen phosphate) phosphate, was obtained under hydro-thermal conditions. In the crystal, two types of [MgO6] octa hedra, one with point group symmetry 2, share edges to build chains extending parallel to [10-1]. These chains are linked together by two kinds of phosphate tetra-hedra, HPO4 and PO4, the latter with point group symmetry 2. The three dimensional framework delimits two different types of channels extending along [001]. One channel hosts the Na(+) cations (site symmetry 2) surrounded by eight O atoms, with Na-O bond lengths varying between 2.2974 (13) and 2.922 (2) A. The OH group of the HPO4 tetra-hedron points into the other type of channel and exhibits a strong hydrogen bond to an O atom of the PO4 tetra-hedron on the opposite side. PMID- 26279889 TI - The crystal structure of 4'-{4-[(2,2,5,5-tetra-methyl-N-oxyl-3-pyrrolin-3 yl)ethyn-yl]phen-yl}-2,2':6',2''-terpyridine. AB - The terpyridine group of the title compound, C31H27N4O, assumes an all-transoid conformation and is essentially planar with the dihedral angles between the mean planes of the central pyridine and the two outer rings amounting to 3.87 (5) and 1.98 (5) degrees . The pyrroline-N-oxyl group commonly seen in such nitroxyls is found in the title structure and the mean plane of the pyrroline ring subtends a dihedral angle of 88.44 (7) degrees to the mean plane of the central pyridine ring. The intra-molecular separation between the nitrogen atom of the central pyridine unit of the terpyridine group and the nitroxyl group is 14.120 (2) A. In the crystal, the mol-ecules are arranged in layers stacked along [001]. Slipped face-to-face pi-pi inter-actions between the pyridine rings are observed along this direction with the shortest centroid-centroid distances amounting to 3.700 (1) and 3.781 (1) A. Furthermore, edge-on C-H?pi inter-actions between the phenyl ene rings of neighbouring mol-ecules are observed along this direction. A two dimensional C-H?O hydrogen-bonded network is formed within the (010) plane. The shortest O?O separation between neighbouring mol-ecules is 5.412 (3) A. PMID- 26279890 TI - Crystal structure of catena-poly[[[tri-aqua-strontium]-di-MU2-glycinato] dibromide]. AB - In the title coordination polymer, {[Sr(C2H5NO2)2(H2O)3]Br2} n , the Sr(2+) ion and one of the water mol-ecules are located on twofold rotation axes. The alkaline earth ion is nine-coordinated by three water O atoms and six O atoms of the carboxyl-ate groups of four glycine ligands, two in a chelating mode and two in a monodentate mode. The glycine mol-ecule exists in a zwitterionic form and bridges the cations into chains parallel to [001]. The Br(-) counter-anions are located between the chains. Inter-molecular hydrogen bonds are formed between the amino and carboxyl-ate groups of neighbouring glycine ligands, generating a head to-tail sequence. Adjacent head-to-tail sequences are further inter-connected by inter-molecular N-H?Br hydrogen-bonding inter-actions into sheets parallel to (100). O-H?Br and O-H?O hydrogen bonds involving the coordinating water mol ecules are also present, consolidating the three-dimensional hydrogen-bonding network. PMID- 26279892 TI - Crystal structure of a second polymorph of 2-cyclo-penta-dienyl-1,7-dicarba-2 cobalta-closo-dodeca-borane(11). AB - A new polymorph of the title compound 2-(eta-C5H5)-2,1,7-closo-CoC2B9H11, [Co(C5H5)(C2H11B9)], in the space group P21/n has been characterized, including the unambiguous location of both cage C atoms. The precision of this study is an order of magnitude greater than that of the first polymorph [C2/c; Lopez et al. (2010). Collect. Czech. Chem. Commun. 75, 853-869]. PMID- 26279893 TI - Crystal structure of [NaZn(BTC)(H2O)4].1.5H2O (BTC = benzene-1,3,5-tri-carb-oxy-l ate): a heterometallic coordination compound. AB - The title coordination polymer, poly[[MU-aqua-tri-aqua-(MU3-benzene-1,3,5-tri carboxyl-ato)sodiumzinc] sesquihydrate], {[NaZn(C9H3O6)(H2O)4].1.5H2O} n , was obtained in ionic liquid microemulsion at room temperture by the reaction of benzene-1,3,5-tri-carb-oxy-lic acid (H3BTC) with Zn(NO3)2.6H2O in the presence of NaOH. The asymmetric unit comprises two Na(+) ions (each located on an inversion centre), one Zn(2+) ion, one BTC ligand, four coordinating water mol-ecules and two solvent water molecules, one of which is disordered about an inversion centre and shows half-occupation. The Zn(2+) cation is five-coordinated by two carboxyl ate O atoms from two different BTC ligands and three coordinating H2O mol-ecules; the Zn-O bond lengths are in the range 1.975 (2)-2.058 (3) A. The Na(+) cations are six-coordinated but have different arrangements of the ligands: one is bound to two carboxyl-ate O atoms of two BTC ligands and four O atoms from four coordinating H2O mol-ecules while the other is bound by four carboxyl-ate O atoms from four BTC linkers and two O atoms of coordinating H2O mol-ecules. The completely deprotonated BTC ligand acts as a bridging ligand binding the Zn(2+) atom and Na(+) ions, forming a layered structure extending parallel to (100). An intricate network of O-H?O hydrogen bonds is present within and between the layers. PMID- 26279895 TI - Crystal structure of 1-[(2,4,6-triiso-propyl-phen-yl)sulfon-yl]aziridine. AB - The title compound, C17H27NO2S, exhibits a distorted geometry of the aromatic ring with elongated bonds at the ipso-C atom. The S atom deviates from the aromatic ring plane by 0.393 (4) A. Similar to this, the adjacent isopropyl groups are bent out of the aromatic ring plane by -0.125 (4) and -0.154 (4) A. Even the distant isopropyl group in para-position to the sulfonyl moiety shows a slight deviation from the ring plane of 0.111 (5) A. These distortions, which are caused by the bulky substituents, can also be observed in related sulfonyl aziridine structures. PMID- 26279891 TI - Redetermination of the crystal structure of beta-zinc molybdate from single crystal X-ray diffraction data. AB - The crystal structure of the beta-polymorph of ZnMoO4 was re-determined on the basis of single-crystal X-ray diffraction data. In comparison with previous powder X-ray diffraction studies [Katikaneani & Arunachalam (2005 ?). Eur. J. Inorg. Chem. pp. 3080-3087; Cavalcante et al. (2013 ?). Polyhedron, 54, 13-25], all atoms were refined with anisotropic displacement parameters, leading to a higher precision with respect to bond lengths and angles. beta-ZnMoO4 adopts the wolframite structure type and is composed of distorted ZnO6 and MoO6 octa-hedra, both with point group symmetry 2. The distortion of the octa-hedra is reflected by variation of bond lengths and angles from 2.002 (3)-2.274 (4) A, 80.63 (11) 108.8 (2) degrees for equatorial and 158.4 (2)- 162.81 (14) degrees for axial angles (ZnO6), and of 1.769 (3)-2.171 (3) A, 73.39 (16)-104.7 (2), 150.8 (2) 164.89 (15) degrees (MoO6), respectively. In the crystal structure, the same type of MO6 octa-hedra share edges to built up zigzag chains extending parallel to [001]. The two types of chains are condensed by common vertices into a framework structure. The crystal structure can alternatively be described as derived from a distorted hexa-gonally closed packed arrangement of the O atoms, with Zn and Mo in half of the octa-hedral voids. PMID- 26279894 TI - Crystal structure of catena-poly[[di-aqua-cobalt(II)]-bis-[MU-5-(4-carb-oxy-ylato phenyl)picolinato]-kappa(3) N,O (2):O (5);kappa(3) O (5):N,O (2)-[di-aqua cobalt(II)]-MU-1-[4-(1H-imidazol-1-yl)phen-yl]-1H-imidazole-kappa(2) N (3):N (3')]. AB - The asymmetric unit of the title polymeric Co(II) complex, [Co2(C13H7NO4)2(C12H10N4)(H2O)4] n , contains a Co(II) cation, a 5-(4-carboxyl atophen-yl)picolinate dianion, two coordination water mol-ecules and half of 1-[4 (1H-imidazol-1-yl)phen-yl]-1H-imidazole ligand. The Co(II) cation is coordinated by two picolinate dianions, two water mol-ecules and one 1-[4-(1H-imidazol-1 yl)phen-yl]-1H-imidazole mol-ecule in a distorted N2O4 octa-hedral coordination geometry. The two picolinate dianions are related by an inversion centre and link two Co(II) cations, forming a binuclear unit, which is further bridged by the imidazole mol-ecules, located about an inversion centre, into the polymeric chain propagating along the [-1-11] direction. In the crystal, the three-dimensional supra-molecular architecture is constructed by O-H?O hydrogen bonds between the coordinating water mol-ecules and the non-coordinating carboxyl-ate O atoms of adjacent polymeric chains. PMID- 26279898 TI - Crystal structure of ethyl 4-(2-meth-oxy-phen-yl)-6-methyl-2-sulfanyl-idene 1,2,3,4-tetra-hydro-pyrimidine-5-carboxyl-ate. AB - In the title compound, C15H18N2O3S, the hydro-pyrimidine ring adopts a sofa conformation with the methine C atom as the flap. The benzene ring is almost perpendicular to the mean plane of the hydro-pyrimidine ring, making a dihedral angle of 85.51 (8) degrees , and the meth-oxy O atom lies over the centre of the pyrimidine ring. In the crystal, weak N-H?S inter-actions form a zigzag chain running along the b-axis direction. PMID- 26279899 TI - Crystal structure of 3,4-di-chloro-anilinium hydrogen phthalate. AB - In the title salt, C6H6Cl2N(+).C8H5O4 (-), the carb-oxy-lic acid and carboxyl-ate groups of the anion form dihedral angles of 20.79 (19) and 74.76 (14) degrees , respectively, with the plane of the benzene ring. In the crystal, mol-ecules are assembled into a two-dimensional polymeric network parallel to (100) via N-H?O and O-H?O hydrogen bonds. In addition, within the layer, there are pi-pi stacking inter-actions between the benzene rings of the cation and the anion [centroid centroid distance = 3.6794 (17) A]. A weak C-H?O interaction is also observed. PMID- 26279900 TI - Crystal structure of benzyl 3-oxo-2-oxa-5-aza-bicyclo-[2.2.1]heptane-5-carboxyl ate. AB - The title compound, C13H13NO4 (also known as N-benzyl-oxycarbonyl-4-hy-droxy-l proline lactone), crystallizes with two mol-ecules in the asymmetric unit. They have slightly different conformations: the fused ring systems almost overlap, but different C-O-C-C torsion angles for the central chains of -155.5 (2) and -178.6 (2) degrees lead to different twists for the terminal benzene ring. In the crystal, the mol-ecules are linked by C-H?O inter-actions, generating a three dimensional network. The absolute structure was established based on an unchanging chiral centre in the synthesis. PMID- 26279903 TI - Cystal structure of N-[2-(benzo[d][1,3]dioxol-5-yl)eth-yl]-4-methyl-benzene sulfonamide. AB - In the title compound, C16H17NO4S, the heterocyclic ring is almost planar (r.m.s. deviation = 0.007A) and the dihedral angle between the benzene rings is 28.18 (10) degrees . The N-C-C-C torsion angle for the central chain is 62.4 (3) degrees : overall, the mol-ecule has a Z-shape. In the crystal, inversion dimers linked by pairs of N-H?O hydrogen bonds generate R 2 (2)(8) loops. PMID- 26279897 TI - Redetermined structure of gossypol (P3 polymorph). AB - An improved crystal structure of the title compound, C30H30O8 (systematic name: 1,1',6,6',7,7'-hexa-hydroxy-5,5'-diisopropyl-3,3'-dimeth-yl[2,2'-bi-naphthalene] 8,8'-dicarbaldehyde), was determined based on modern CCD data. Compared to the previous structure [Talipov et al. (1985). Khim. Prirod. Soedin. (Chem. Nat. Prod.), 6, 20-24], geometrical precision has been improved (typical C-C bond distance s.u. = 0.002 A in the present structure compared to 0.005 A in the previous structure) and the locations of several H atoms have been corrected. The gossypol mol-ecules are in the aldehyde tautomeric form and the dihedral angle between the naphthyl fragments is 80.42 (4) degrees . Four intra-molecular O-H?O hydrogen bonds are formed. In the crystal, inversion dimers with graph-set motif R 2 (2)(20) are formed by pairs of O-H?O hydrogen bonds; another pair of O-H?O hydrogen bonds with the same graph-set motif links the dimers into [001] chains. The packing of such chains in the crystal leads to the formation of channels (diameter = 5-8 A) propagating in the [101] direction. The channels presumably contain highly disordered solvent mol-ecules; their contribution to the scattering was removed with the SQUEEZE [Spek (2015). Acta Cryst. C71, 9-18] routine in PLATON and the stated mol-ecular mass, density etc., do not take them into account. PMID- 26279896 TI - Crystal structure of (4Z)-4-[(di-methyl-amino)-methyl-idene]-3,5-dioxo-2-phenyl pyrazolidine-1-carbaldehyde. AB - In the title compound, C13H13N3O3, the pyrazolidine ring adopts a shallow envelope conformation, with the carbonyl C atom closest to the benzene ring as the flap [deviation of 0.126 (1) A from the plane through the remaining atoms (r.m.s. deviation = 0.011 A)]. The dihedral angle between the pyrazolidine ring (all atoms) and the benzene ring is 51.09 (4) degrees . An extremely short (2.08 A) intra-molecular C-H?O contact is seen. In the crystal, mol-ecules are linked by C-H?O bonds, generating [010] chains. Extremely weak C-H?pi inter-actions are also observed. PMID- 26279902 TI - Crystal structure of 2-methyl-3-nitro-benzoic anhydride. AB - The title mol-ecule, C16H12N2O7, lies on a twofold rotation axis which bis-ects the central O atom. The dihedral angle between two symmetry-related benzene rings is 48.54 (9) degrees . In the crystal, mol-ecules are linked by weak C-H?O hydrogen bonds which generate C(13) chains running parallel to [31-1]. PMID- 26279901 TI - Crystal structure of (1R,4R)-tert-butyl 3-oxo-2-oxa-5-aza-bicyclo-[2.2.2]octane-5 carboxyl-ate. AB - In the title compound, C11H17NO4, commonly known as N-tert-but-oxy-carbonyl-5-hy droxy-d-pipecolic acid lactone, the absolute configuration is (1R,4R) due to the enantiomeric purity of the starting material which remains unchanged during the course of the reaction. In the crystal there no inter-molecular hydrogen bonds. PMID- 26279905 TI - Crystal structure of 2-cyano-N-(furan-2-ylmeth-yl)acetamide. AB - In the title compound, C8H8N2O2, the acetamide unit is inclined to the furan ring by 76.7 (1) degrees . In the crystal, mol-ecules are linked by N-H?O and C-H?O hydrogen bonds, generating C(4) chains along [100]. The carbonyl O atom is a bifurcated acceptor and an R (1) 2(6) ring is formed. PMID- 26279907 TI - Crystal structure of (E)-1,2-bis-(4-bromo-2,6-di-fluoro-phen-yl)diazene. AB - In the crystal, mol-ecules of the centrosymmetric title compound, C12H4Br2F4N2, are linked into strands along [011] by weak C-H?F contacts. Furthermore, the mol ecules are pi-pi stacked with perpendicular ring distances of 3.4530 (9) A. PMID- 26279904 TI - Crystal structure of 6-amino-4-(3-bromo-4-meth-oxy-phen-yl)-3-methyl-2,4-di-hydro pyrano[2,3-c]pyrazole-5-carbo-nitrile dimethyl sulfoxide monosolvate. AB - In the pyrazole mol-ecule of the title solvate, C15H13BrN4O2.C2H6OS, the dihedral angle between the benzene ring and the mean plane of the di-hydro-pyrano[2,3 c]pyrazole ring system [r.m.s deviation = 0.031 (2) A] is 86.71 (14) degrees . In the crystal, the pyrazole mol-ecules are linked by N-H?N hydrogen bonds, forming a layer parallel to (10-1). The pyrazole and dimethyl sulfoxide mol-ecules are connected by an N-H?O hydrogen bond. PMID- 26279906 TI - Crystal structure of obscurine: a natural product isolated from the stem bark of B. obscura. AB - The title compound, C24H31NO3 {systematic name: (E)-3-[(1R*,2S*,4aS*,8aR*)-2 (benzo[d][1,3]dioxol-5-yl)-1,2,4a,5,6,7,8,8a-octa-hydro-naphthalen-1-yl]-N-iso butyl-acryl-amide}, is a natural product isolated from the stem bark of B. obscura. It is composed of an octa-hydro-naphthalene ring system substituted with an essentially planar benzodioxole ring system [r.m.s. deviation = 0.012 A] and an extended iso-butyl-acryl-amide group. In the crystal, mol-ecules are linked by N-H?O hydrogen bonds, forming chains propagating along [100]. The chains are linked by pairs of C-H?O hydrogen bonds, involving inversion-related benzodioxole ring systems, forming ribbons lying parallel to (010). There are also C-H?pi inter-actions present within the ribbons. PMID- 26279908 TI - Crystal structure of pymetrozine. AB - The title compound, C10H11N5O {systematic name: 6-methyl-4-[(E)-(pyridin-3-yl methyl-idene)amino]-4,5-di-hydro-1,2,4-triazin-3(2H)-one}, C10H11N5O, is used as an anti-feedant in pest control. The asymmetric unit comprises two independent mol-ecules, A and B, in which the dihedral angles between the pyridinyl and triazinyl ring planes [r.m.s. deviations = 0.0132 and 0.0255 ] are 11.60 (6) and 18.06 (4) degrees , respectively. In the crystal, N-H?O, N-H?N, C-H?N and C-H?O hydrogen bonds, together with weak pi-pi inter-actions [ring-centroid separations = 3.5456 (9) and 3.9142 (9) A], link the pyridinyl and triazinyl rings of A mol ecules, generating a three-dimensional network. PMID- 26279909 TI - Crystal structure of the pyridine-diiodine (1/1) adduct. AB - In the title adduct, C5H5N.I2, the N-I distance [2.424 (8) A] is remarkably shorter than the sum of the van der Waals radii. The line through the I atoms forms an angle of 78.39 (16) degrees with the normal to the pyridine ring. PMID- 26279910 TI - Crystal structure of 16-hy-droxy-4,4,10,13,14-penta-methyl-17-(6-methyl-hept-5-en 2-yl)-4,5,6,9,10,11,12,13,14,15,16,17-dodeca-hydro-1H-cyclo-penta-[a]phenanthren 3(2H)-one. AB - The title compound, C30H48O2, contains a fused four-ring triterpenoid system. In the mol-ecule, the two cyclo-hexane rings adopt a chair conformation and a twist boat conformation, respectively, the central cyclo-hexene ring adopts a half chair conformation whereas the five membered ring adopts an envelope conformation. In the crystal, O-H?O hydrogen bonds between the hy-droxy and carbonyl groups of adjacent mol-ecules link the mol-ecules into supra-molecular chains propagating along the b-axis direction. PMID- 26279911 TI - Crystal structure of 2-{[2-meth-oxy-5-(tri-fluoro-meth-yl)phen-yl]iminomethyl}-4 nitro-phenol. AB - In the title compound, C15H11F3N2O4, the N=C bond of the central imine group adopts an E conformation. The dihedral angle between two benzene rings is 6.2 (2) degrees . There is an intra-molecular bifurcated O-H?(N,O) hydrogen bond with S(6) and S(9) ring motifs. In the crystal, mol-ecules are linked by C-H?O hydrogen bonds into a helical chain along the 31 screw axis parallel to c. The CF3 group shows rotational disorder over two sites, with occupancies of 0.39 (2) and 0.61 (2). PMID- 26279912 TI - Crystal structure of 3-amino-1-(4-meth-oxy-phen-yl)-1H-benzo[f]chromene-2-carbo nitrile. AB - In the title compound, C21H16N2O2, the meth-oxy-benzene ring is almost perpendicular to the mean plane of the naphthalene ring system, making a dihedral angle of 83.62 (5) degrees . The 4H-pyran ring fused with the naphthalene ring system is almost planar [maximum deviation = 0.033 (1) A]. In the crystal, mol ecules are linked into inversion dimers by pairs of N-H?N hydrogen bonds. N-H?O hydrogen bonds connect the dimers, forming a helical supra-molecular chain along the a-axis direction. The crystal packing also features C-H?pi inter-actions. PMID- 26279914 TI - Crystal structure of cis-anti-cis-di-cyclo-hexane-18-crown-6 aceto-nitrile disolvate. AB - The title compound (systematic name: cis-anti-cis-2,5,8,15,18,21-hexa-oxatri cyclo-[20.4.0.0(9,14)]hexa-cosane aceto-nitrile disolvate), C20H36O6.2CH3CN, crystallizes from an aceto-nitrile solution of di-cyclo-hexane-18-crown-6 on evaporation. The mol-ecule is arranged around a center of symmetry with half the crown ether mol-ecule and one mol-ecule of aceto-nitrile symmetry independent. All O-C-C-O torsion angles are gauche while all C-O-C-C angles are trans. The sequence of torsion angles is [(tg(+)t)(tg(-)t)]3; the geometry of oxygen atoms is close to pseudo-D 3d with three atoms below and three atoms above the mean plane, with an average deviation of +/-0.16 (1) A from the mean plane. This geometry is identical to that observed in metal ion complexes of di-cyclo-hexane 18-crown-6 but differs significantly from the conformation of a free unsolvated mol-ecule. Each aceto-nitrile mol-ecule connects to a crown ether mol-ecule via two of its methyl group H atoms (C-H?O). Weaker inter-actions exist between the third H atom of the aceto-nitrile methyl group and an O atom of a neighbouring crown ether mol-ecule (C-H?O); and between the N atom of the aceto-nitrile mol ecule and a H atom of another neighbouring crown ether mol-ecule. All these inter molecular inter-actions create a three-dimensional network stabilizing the disolvate. PMID- 26279913 TI - Crystal structure of azimsulfuron. AB - The title compound {systematic name: 1-(4,6-di-meth-oxy-pyrimidin-2-yl)-3-[1 methyl-4-(2-methyl-2H-tetra-zol-5-yl)pyrazol-5-ylsulfon-yl]urea}, C13H16N10O5S, is a sulfonyl-urea herbicide. In this compound, the dihedral angles between the planes of the central pyrazole and the terminal di-meth-oxy-pyrimidine and tetra zole rings are 79.10 (8) and 17.21 (16) degrees , respectively. In the crystal, N H?O hydrogen bonds link adjacent mol-ecules, forming R 2 (2)(8) inversion dimers. In addition, weak C-H?O and C-H?N hydrogen bonds and weak pi-pi inter-actions [ring centroid separation = 3.8255 (12) A] are present, resulting in a three dimensional architecture. PMID- 26279915 TI - Crystal structure of 3-acet-oxy-2-methyl-benzoic acid. AB - In the title mol-ecule, C10H10O4, the carb-oxy-lic acid group is twisted by 11.37 (15) degrees from the plane of the benzene ring and the acet-oxy group is twisted from this plane by 86.60 (17) degrees . In the crystal, mol-ecules are linked by pairs of O-H?O hydrogen bonds, forming inversion dimers with the expected R 2 (2)(8) graph-set motif. PMID- 26279916 TI - Crystal structure of 4-methyl-benzyl N'-[(thio-phen-2-yl)methyl idene]hydrazinecarbodi-thio-ate. AB - In the title compound, C15H16N2S3 {systematic name: [({[(4-methyl-phen-yl)meth yl]sulfan-yl}methane-thio-yl)amino][1-(thio-phen-2-yl)ethyl-idene]amine}, the central CN2S2 residue is almost planar (r.m.s. deviation = 0.0061 A) and forms dihedral angles of 7.39 (10) and 64.91 (5) degrees with the thienyl and p-tolyl rings, respectively; the dihedral angle between these rings is 57.52 (6) degrees . The non-thione S atoms are syn, and with respect to the thione S atom, the benzyl group is anti. In the crystal, centrosymmetrically related mol-ecules self associate via eight-membered {?HNCS}2 synthons. The dimeric aggregates stack along the a axis and are are consolidated into a three-dimensional architecture via methyl-C-H?pi(benzene) and benzene-C-H?pi(thien-yl) inter-actions. PMID- 26279917 TI - Crystal structure of ethyl 2-acetyl-3,7-dimethyl-5-(thio-phen-2-yl)-5H-thia zolo[3,2-a]pyrimidine-6-carboxyl-ate. AB - In the title compound, C17H18N2O3S2, the pyrimidine ring adopts a shallow sofa conformation, with the C atom bearing the axially-oriented thio-phene ring as the flap [deviation = 0.439 (3) A]. The plane of the thio-phene ring lies almost normal to the pyrimidine ring, making a dihedral angle of 79.36 (19) degrees . In the crystal, pairs of very weak C-H?O hydrogen bonds link the mol-ecules related by twofold rotation axes, forming R 2 (2)(18) rings, which are in turn linked by another C-H?O inter-action, forming chains of rings along [010]. In addition, weak C-H?pi(thio-phene) inter-actions link the chains into layers parallel to [001] and pi-pi inter-actions with a centroid-centroid distance of 3.772 (10) A connect these layers into a three-dimensional network. PMID- 26279918 TI - Crystal structure of 2-amino-4,6-di-meth-oxy-pyrimidinium thio-phene-2-carboxyl ate. AB - In the title salt, C6H10N3O2 (+).C5H3O2S(-), the 2-amino-4,6-di-meth-oxy pyrimidinium cation inter-acts with the carboxyl-ate group of the thio-phene-2 carboxyl-ate anion through a pair of N-H?O hydrogen bonds, forming an R 2 (2)(8) ring motif. These motifs are centrosymmetrically paired via N-H?O hydrogen bonds, forming a complementary DDAA array. The separate DDAA arrays are linked by pi-pi stacking inter-actions between the pyrimidine rings, as well as by a number of weak C-H?O and N-H?O inter-actions. In the anion, the dihedral angle between the ring plane and the CO2 group is 11.60 (3) degrees . In the cation, the C atoms of methoxy groups deviate from the ring plane by 0.433 (10) A. PMID- 26279919 TI - Crystal structure of 3-amino-1-(4-chloro-phen-yl)-1H-benzo[f]chromene-2-carbo nitrile. AB - In the title compound, C20H13ClN2O, the chloro-benzene ring is almost perpendicular to the mean plane of the naphthalene ring system, making a dihedral angle of 81.26 (8) degrees . The 4H-pyran ring fused with the naphthalene ring system has a flattened boat conformation. In the crystal, N-H?N hydrogen bonds generate chains along the b-axis direction. Further N-H?N hydrogen bonds link these chains into sheets parallel to (010). The crystal packing also features C H?pi inter-actions. The crystal studied was an inversion twin with a 0.557 (16):0.443 (16) domain ratio. PMID- 26279920 TI - Crystal structure of 15,16-ep-oxy-7beta,9alpha-di-hydroxy-labdane-13(16),14-dien 6-one. AB - In the title mol-ecule, C20H30O4, both cyclo-hexane rings adopt chair conformations. In the crystal, mol-ecules are connected by O-H?O hydrogen bonds forming chains along [100]. In addtion, an intra-molecular O-H?O hydrogen bond forms an S(5) ring. PMID- 26279921 TI - Crystal structure of (E)-5,5-dimethyl-2-[3-(4-nitro-phen-yl)allyl-idene]cyclo hexane-1,3-dione. AB - In the title compound, C17H17NO4, the cylohexane-1,3-dione ring adopts an envelope conformation with the dimethyl-subsituted C atom as the flap. Its mean plane is inclined to the benzene ring by 7.99 (19) degrees . The mol-ecule has a trans conformation about the bridging C=C bonds of the ally-idene chain. In the crystal, mol-ecules are linked via pairs of C-H?O hydrogen bonds, forming inversion dimers. The dimers are linked by further C-H..O hydrogen bonds, forming sheets lying parallel to (10-1). PMID- 26279922 TI - Crystal structure of 1,2-di-benzoyl-ace-naphthyl-ene. AB - The title mol-ecule, C26H16O2, crystallizes as a mol-ecular crystal with no strong inter-molecular inter-actions (the shortest C-H?O contact is longer than 3.4 A). Two flat ace-naphthyl-ene groups of neigboring 1,2-di-benzoyl-ace naphthyl-ene mol-ecules are related by a crystallographic center of symmetry and are stacked with the distance between their mean planes of 3.37 (1) A, apparently making an optimal close packing for these bulky aromatic moieties. Both carbonyl groups are oriented towards the same side of the planar ace-naphthyl-ene. The angles between the flat ace-naphthyl-ene group and the benzoyl groups are 62.6 (1) and 57.8 (1) degrees . Because rotation of the benzoyl groups is sterically hindered, we expect that the mol-ecules will remain locked in this 'pseudo-cis' orientation in solution. As a result, reduction of 1,2-di-benzoyl-ace-naphthyl ene at low temperature with sodium di-thio-nite yields the cis-isomer of 1,2 dibenzoyl-1,2-di-hydro-ace-naphthyl-ene, which is sterically favorable. This isomer is thermodynamically less favorable than the trans isomer, but it converts to the more stable isomer only on long-term heating (Greenberg & Schenendorf (1980 ?). PMID- 26279924 TI - Crystal structure of 2-diazo-imidazole-4,5-dicarbo-nitrile. AB - In the title compound, C5N6, all the atoms are approximately coplanar. In the crystal, mol-ecules are packed with short contact distances of 2.885 (2) (between the diazo N atom connected to the ring and a cyano N atom on a neighboring mol ecule) and 3.012 (2) A (between the terminal diazo N atom and an N atom of a neighboring imidazole ring). PMID- 26279923 TI - Crystal structure of (6-bromo-2-oxo-2H-chromen-4-yl)methyl morpholine-4-carbodi thio-ate. AB - In the title compound, C15H14BrNO3S2, the 2H-chromene ring system is nearly planar, with a maximum deviation of 0.034 (2) A, and the morpholine ring adopts a chair conformation. The dihedral angle between best plane through the 2H-chromene ring system and the morpholine ring is 86.32 (9) degrees . Intra-molecular C-H?S hydrogen bonds are observed. In the crystal, inversion-related C-H?S and C-H?O inter-actions generate R 2 (2)(10) and R 2 (2)(8) rings patterns, respectively. In addition, the crystal packing features pi-pi inter-actions between fused benzene rings [centroid-centroid distance = 3.7558 (12) A]. PMID- 26279925 TI - Crystal structure of 5-(1-benzo-furan-2-yl)-3-(4-methyl-phen-yl)-4,5-di-hydro-1,2 oxazol-5-ol. AB - In the title compound, C18H15NO3, the isoxazole moiety adopts a shallow envelope conformation, with the C atom bearing the OH group displaced by 0.148 (1) A from the mean plane through the other four atoms. The mean plane of this ring (all atoms) subtends dihedral angles of 87.19 (6) and 15.51 (7) degrees with the benzo-furan ring system (r.m.s. deviation = 0.007 A) and the 4-methylphenyl ring, respectively. In the crystal, mol-ecules are linked by O-H?N hydrogen bonds, generating [001] C(5) chains, with adjacent mol-ecules in the chain related by c glide symmetry. Weak C-H?O inter-actions link the chains into a three-dimensional network. PMID- 26279926 TI - Crystal structure of oxadiarg-yl. AB - In the title compound {systematic name: 5-tert-butyl-3-[2,4-di-chloro-5-(prop-2 yn-yloxy)phen-yl]-1,3,4-oxa-diazol-2(3H)-one}, C15H14Cl2N2O3, which is an oxa diazo-lone herbicide, the dihedral angle between the planes of the oxa-diazo-lone and benzene rings is 65.84 (6) degrees . In the crystal, weak inter-molecular Cl?Cl [3.3600 (7) A] short contacts link adjacent mol-ecules, forming chains along the b-axis direction. These chains are linked by C-H?O, C-H?N and C-H?Cl hydrogen bonds, generating a three-dimensional network. Weak C-H?pi inter-actions are also present. PMID- 26279927 TI - Crystal structure of 3-(hy-droxy-meth-yl)chromone. AB - In the title compound, C10H8O3 (systematic name 3-hy-droxy-methyl-4H-chromen-4 one), the fused-ring system is slightly puckered [dihedral angle between the rings = 3.84 (11) degrees ]. The hy-droxy O atom deviates from the heterocyclic ring by 1.422 (1) A. In the crystal, inversion dimers linked by pairs of O-H?O hydrogen bonds generate R 2 (2)(12) loops. The dimers are linked by aromatic pi pi stacking [shortest centroid-centroid distance = 3.580 (3) A], and C-H?O hydrogen bonds, generating a three-dimensional network. PMID- 26279928 TI - Crystal structure of (E)-1-{[(3,5-di-methyl-phen-yl)imino]-meth-yl}naphthalen-2 ol. AB - The title compound, C19H17NO, has an E conformation about the N=C bond. The mol ecule is relatively planar, with the benzene ring and naphthalene ring plane being inclined to one another by 4.28 (10) degrees . There is an intra-molecular O-H?N hydrogen bond generating an S(6) ring motif. In the crystal, mol-ecules are linked via C-H?O hydrogen bonds, forming chains propagating along [100]. Within the chains there are pi-pi inter-actions involving the benzene ring and the naphthalene ring system of an adjacent mol-ecule [inter-centroid distance = 3.6405 (14) A]. PMID- 26279929 TI - Crystal structure of N-[(morpholin-4-yl)(thio-phen-2-yl)meth-yl]benzamide. AB - In the title compound, C16H18N2O2S, the morpholine ring adopts a chair conformation. The thio-phene ring makes a dihedral angle of 63.54 (14) degrees with the mean plane of the four C atoms [maximum deviation = 0.010 (3) A] of the morpholine ring. The benzamide ring is disordered, with four C atoms occupying two sets of sites, with a refined occupancy ratio of 0.502 (4):0.498 (4). These two rings are inclined to one another by 85.2 (4) degrees and to the thio-phene ring by 72.7 (3) and 13.0 (3) degrees for the major and minor components, respectively. In the crystal, mol-ecules are linked via N-H?O hydrogen bonds, forming chains along [001]. PMID- 26279930 TI - Crystal structure of (E)-4,4'-(but-2-ene-1,4-di-yl)bis-(2-meth-oxy-phenol). AB - The title compound, C18H20O4, was synthesized via the ruthenium-catalyzed alkene methathesis dimerization of eugenol. The whole mol-ecule is generated by inversion symmetry; the center of inversion being located at the mid-point of the trans C=C bond. The phenol ring is inclined to the mean plane of the central C C=C-C unit (r.m.s. deviation = 0.014 A) by 68.83 (16) degrees . In the crystal, mol-ecules are linked via O-H?O hydrogen bonds, involving the hy-droxy and meth oxy groups, forming undulating sheets parallel to (010). PMID- 26279931 TI - Crystal structure of (2-hy-droxy-5-methyl-phen-yl)(3-methyl-1-phenyl-1H-pyrazolo [3,4-b]pyridin-5-yl)methanone. AB - In the title compound, C21H17N3O2, the 2-hy-droxy-5-methyl-phenyl ring and the phenyl ring are inclined to the mean plane of the pyrazolo-pyridine moiety (r.m.s. deviation = 0.013 A) by 52.89 (9) and 19.63 (8) degrees , respectively, and to each other by 42.83 (11) degrees . In the mol-ecule, there are intra molecular O-H?O and C-H?N hydrogen bonds, both enclosing an S(6) ring motif. In the crystal, mol-ecules stack along the c-axis direction, forming columns within which there are a number of pi-pi inter-actions [the inter-centroid distances vary from 3.5278 (10) to 3.8625 (10) A]. The columns are linked by C-H?pi inter actions, forming slabs parallel to (100). PMID- 26279932 TI - Crystal structure of (E)-5-di-ethyl-amino-2-({[4-(di-methyl-amino)-phen-yl]imino} meth-yl)phenol. AB - The title Schiff base compound, C19H25N3O, is approximately planar, with a dihedral angle of 9.03 (13) degrees between the planes of the aromatic rings, and has an E conformation about the N=C bond. The mol-ecular structure is stabilized by an intra-molecular O-H?N hydrogen bond, with an S(6) ring motif. In the crystal, mol-ecules are linked by C-H?pi inter-actions, forming sheets parallel to the bc plane. PMID- 26279933 TI - Crystal structure of 1,4-dieth-oxy-9,10-anthra-quinone. AB - The asymmetric unit of the title compound, C18H16O4, contains two crystallographically independent mol-ecules. The anthra-quinone ring systems are slightly bent with dihedral angles of 2.33 (8) and 13.31 (9) degrees between the two terminal benzene rings. In the crystal, the two independent mol-ecules adopt slipped-parallel pi-overlap with an average inter-planar distance of 3.45 A, forming a dimer; the centroid-centroid distances of the pi-pi inter-actions are 3.6659 (15)-3.8987 (15) A. The mol-ecules are also linked by C-H?O inter-actions, forming a tape structure along the a-axis direction. The crystal packing is characterized by a dimer-herringbone pattern. PMID- 26279934 TI - Crystal structure of 1,2-bis-(2,6-di-methyl-phen-yl)-3-phenyl-guanidine. AB - In the title compound, C23H25N3, the dihedral angles between the planes of the benzene ring and the two substituent di-methyl-phenyl rings are 60.94 (7) degrees and 88.08 (7) degrees , and the dihedral angle between the planes of the two di methyl-phenyl rings is 58.01 (7) degrees . In the crystal, weak C-H?N inter actions exist between adjacent mol-ecules. One of the di-methyl-phenyl rings has a small amount of pi-pi overlap with the phenyl ring of an adjacent mol-ecule [centroid-to-centroid distance = 3.9631 (12) A]. PMID- 26279935 TI - Crystal structure of N-[(naphthalen-1-yl)carbamo-thio-yl]cyclo-hexa necarboxamide. AB - The title compound, C18H20N2OS, displays whole-mol-ecule disorder over two adjacent sets of sites with an occupancy ratio of 0.630 (11):0.370 (11). In each disorder component, the cyclo-hexyl ring shows a chair conformation with the exocyclic C-C bond in an equatorial orientation. The dihedral angles between the cyclo-hexyl ring (all atoms) and the naphthyl ring system are 36.9 (6) for the major component and 20.7 (12) degrees for the minor component. Each component features an intra-molecular N-H?O hydrogen bond, which closes an S(5) ring. In the crystal, inversion dimers linked by pairs of N-H?S hydrogen bonds generate R (2) 2(8) loops for both components. Aromatic pi-pi stacking inter-actions [shortest centroid-centroid separation = 3.593 (9) A] and a C-H?pi inter-action are also observed. PMID- 26279936 TI - Crystal structure of 1'-(prop-2-yn-1-yl)-1,4-di-hydro-spiro-[benzo[d][1,3]oxazine 2,3'-indolin]-2'-one. AB - In the title compound, C18H14N2O2, the six-membered oxazine ring adopts a half chair conformation and its mean plane makes a dihedral angle of 83.23 (7) degrees with the pyrrolidine ring of the indoline ring system. In the crystal, mol ecules are linked via N-H?O hydrogen bonds, forming chains along [100]. The chains are linked by C-H?pi inter-actions, forming slabs parallel to (001). PMID- 26279937 TI - Crystal structure of 4-(6-chloro-4-oxo-4H-chromen-3-yl)-2-methyl-amino-3-nitro 4H,5H-pyrano[3,2-c]chromen-5-one chloro-form monosolvate. AB - In the title compound, C23H14Cl4N2O7, the pyran ring has an envelope conformation with the methine C atom as the flap. The chromene rings are almost planar (r.m.s. deviations of 0.027 and 0.018 A) and their mean planes are inclined to one another by 85.61 (10) degrees . The mean planes of the pyran ring and the chromene ring fused to it are inclined to one another by 7.41 (13) degrees . The mol-ecular structure is stabilized by an intra-molecular N-H?O hydrogen bond, generating an S(6) ring motif. In the crystal, mol-ecules are linked by pairs of N-H?O hydrogen bonds, forming inversion dimers with an R (2) 2(12) ring motif. The dimers are linked by pairs of C-H?O hydrogen bonds, enclosing R (2) 2(18) ring motifs, forming chains along [010]. Within the chains there are C-H?pi inter actions. The chains are linked via slipped parallel pi-pi inter-actions, forming a three-dimensional structure [the shortest inter-centroid distance is 3.7229 (19) A]. PMID- 26279938 TI - Crystal structure of ethyl 2-(2,4,5-tri-meth-oxy-phen-yl)quinoline-4-carboxyl ate. AB - In the title compound, C21H21NO5, the dihedral angle between the quinoline ring system (r.m.s. deviation = 0.028 A) and the tri-meth-oxy-benzene ring is 43.38 (5) degrees . The C atoms of the meth-oxy groups deviate from their attached benzene ring by -0.396 (2), -0.049 (2) and 0.192 (2) A for the ortho-, meta- and para-substituents, respectively. The pendant ethyl chain is disordered over two orientations in a 0.527 (5):0.473 (5) ratio. A short intra-molecular C-H?O contact closes an S(6) ring. In the crystal, inversion dimers linked by pairs of weak C-H?O inter-actions generate R 2 (2)(6) loops. The dimers are linked by further C-H?O inter-actions to generate [1-10] chains. PMID- 26279939 TI - Crystal structure of 2-amino-4-phenyl-4H-benzo[h]chromene-3-carbo-nitrile. AB - In the title compound, C20H14N2O, the plane of the phenyl ring is almost normal to that of the naphthalene ring system, forming a dihedral angle of 83.15 (8) degrees . The 4H-pyran ring fused with the naphthalene ring system has a flattened boat conformation. In the crystal, mol-ecules are linked by pairs of N H?N hydrogen bonds, forming inversion dimers with an R 2 (2)(12) ring motif. The dimers are connected by C-H?pi inter-actions, forming supra-molecular chains along [010]. PMID- 26279940 TI - Crystal structure of 4alpha-hy-droxy-5alpha,8beta(H)-eudesm-7(11)-en-8,12-olide monohydrate. AB - The title compound, C15H22O3.H2O, is a natural producr isolated from Chloranthus japonicus, which is a eudesmane sesquiterpenoid. The two trans-fused six-membered rings have chair confomations. In the crystal, O-H?O hydrogen bonds link the components into corrugated layers parallel to the bc plane. There are C-H?O inter actions present within and between the layers. PMID- 26279941 TI - Crystal structure of ethyl (4R)-2-amino-7-hy-droxy-4-phenyl-4H-chromene-3 carboxyl-ate. AB - In the title compound, C18H17NO4, the dihedral angle between the phenyl ring and the fused six-membered ring is 77.65 (4) degrees . The conformation of the mol ecule is determined in part by an intra-molecular N-H?O hydrogen bond between the amino H atom and the carbonyl O atom, forming an S(6) motif. In the crystal, mol ecules are linked into N-H?O hydrogen-bonded inversion dimers which are then connected into chains along [001], forming a two-dimensional network parallel to (100) via O-H?O hydrogen bonds. C-H?O interactions further contribute to the crystal stability. The ethyl group is disordered over two sets of sites in a 0.801 (5):0.199 (5) ratio. PMID- 26279942 TI - Crystal structure of 11-[4-(hex-yloxy)phen-yl]-1,2,4-triazolo[4,3 a][1,10]phenanthroline. AB - The title compound, C25H24N4O, was prepared from 2-chloro-phenanthroline and hexyl-oxyphenyl-tetra-zole. The main difference between the two independent mol ecules (A and B) in the asymmetric unit is the orientation of the all-anti configured hex-yloxy chain: in A the C-O-C-C torsion angle is 175.9 (2) degrees whereas it is -88.3 (3) degrees in B. The benzene substitution in the bay of the triazolophenanthroline results in a helical distorsion of the heterocyclic core, the dihedral angles between the mean planes formed by quinoline and benzotriazole ring systems are 13.73 (9) for mol-ecule A and 14.87 (8) degrees for B. The dihedral angles between the triazole ring and the attached benzene ring are 45.87 (15) in A and 53.93 (14) degrees in B. The angular annulation of four rings and the benzene substituent results in a helical distortion of the aromatic framework. The crystal is formed from layers composed of centrosymmetric pairs of A 2, B 2 mol-ecules with inter-digitating alkyl chains. PMID- 26279943 TI - Crystal structure of 3-bromo-2-hy-droxy-benzo-nitrile. AB - The crystal structure of the title compound, C7H4BrNO, has been determined, revealing a partial mol-ecular packing disorder such that a 180 degrees rotation of the mol-ecule about the phenol C-O bond results in disorder of the bromine and nitrile groups. The disorder has been parameterized as a disorder of only the bromine and nitrile substituents on a unique phenol ring. An intra-molecular O H?Br contact occurs. In the crystal, O-H?Br/O-H?Nnitrile hydrogen bonding is present between the disordered bromine and nitrile substituents and the phenol group, forming a spiral chain about a twofold screw axis extending parallel to the b-axis direction. Within this spiral chain, the mol-ecules also inter-act, forming offset face-to-face pi-stacking inter-actions with plane-to-centroid distance of 3.487 (1) A. PMID- 26279944 TI - Crystal structure of 3,9,9-trimethyl-2,3,3a,4,9,9a-hexa-hydro-1H-cyclo penta[b]quinolin-4-ium chloride. AB - The title mol-ecular salt, C15H22N(+).Cl(-), arose as an unexpected product of the reaction between aniline and melanol in the presence of HCl. The central heterocyclic ring has a half-chair conformation and the five-membered ring has an envelope conformation, with the C atom linked to the N atom as the flap. In the crystal, the ions are linked by N-H?Cl hydrogen bonds, generating chains propagating in the [100] direction. The crystal studied was a merohedral twin with a 0.64 (3):0.36 (3) domain ratio. PMID- 26279945 TI - Crystal structure of (E)-dodec-2-enoic acid. AB - The crystal structure of (E)-dodec-2-enoic acid, C12H22O2, an alpha,beta unsaturated carb-oxy-lic acid with a melting point (295 K) near room temperature, is characterized by carb-oxy-lic acid inversion dimers linked by pairs of O-H?O hydrogen bonds. The carb-oxy-lic acid group and the following three carbon atoms of the chain of the (E)-dodec-2-enoic acid mol-ecule lie almost in one plane (r.m.s. deviation for the four C atoms and two O atoms = 0.012 A), whereas the remaining carbon atoms of the hydro-carbon chain adopt a nearly fully staggered conformation [moduli of torsion angles vary from 174.01 (13) to 179.97 (13) degrees ]. PMID- 26279946 TI - Crystal structure of [(E)-({2-[3-(2-{(1E)-[(carbamo-thioyl-amino)-imino]-meth yl}phen-oxy)prop-oxy]phen-yl}methyl-idene)amino]-thio-urea with an unknown solvate. AB - The title mol-ecule, C19H22N6O2S2, has crystallographically imposed C 2 symmetry, with the central C atom lying on the rotation axis. The O-C-C-C torsion angle for the central chain is -59.22 (16) degrees and the dihedral angle between the planes of the benzene rings is 75.20 (7) degrees . In the crystal, N-H?O and N H?S inter-actions link the mol-ecules, forming a three-dimensional network encompassing channels running parallel to the c axis, which account for about 20% of the unit-cell volume. The contribution to the scattering from the highly disordered solvent mol-ecules in these channels was removed with the SQUEEZE routine [Spek (2015). Acta Cryst. C71, 9-18] in PLATON. The stated crystal data for M r, MU etc. do not take these into account. PMID- 26279947 TI - Histone deacetylase inhibition protects hearing against acute ototoxicity by activating the Nf-kappaB pathway. AB - Auditory hair cells have repeatedly been shown to be susceptible to ototoxicity from a multitude of drugs including aminoglycoside antibiotics. Here, we found that systemic HDAC inhibition using suberoylanilide hydroxamic acid (SAHA) on adult mice offers almost complete protection against hair cell loss and hearing threshold shifts from acute ototoxic insult from kanamycin potentiated with furosemide. We also found that the apparent lack of hair cell loss was completely independent of spontaneous or facilitated (ectopic Atoh1 induction) hair cell regeneration. Rather, SAHA treatment correlated with RelA acetylation (K310) and subsequent activation of the Nf-kappaB pro-survival pathway leading to expression of pro-survival genes such as Cflar (cFLIP) and Bcl2l1 (Bcl-xL). In addition, we also detected increased expression of pro-survival genes Cdkn1a (p21) and Hspa1a (Hsp70), and decreased expression of the pro-apoptosis gene Bcl2l11 (Bim). These data combined provide evidence that class I HDACs control the transcriptional activation of pro-survival pathways in response to ototoxic insult by regulating the acetylation status of transcription factors found at the crossroads of cell death and survival in the mammalian inner ear. PMID- 26279949 TI - Value of Analog in Medicine: Digital Compromise to Teach Old-Timer New Trick. PMID- 26279948 TI - The Role of Community Health Workers in the Re-Engineering of Primary Health Care in Rural Eastern Cape. AB - BACKGROUND: Primary Health Care in South Africa is being re-engineered to create a model of integrated care across different levels of the health care system. From hospitals to clinics, in the community and in the home, health care will focus more on prevention, health-promotion and advocacy for healthy lifestyles and wellbeing, in addition to clinical services. We provide a best practise model of integrating community health workers (CHWs) trained as generalists into a multi-level health system in the Oliver Tambo district of the rural Eastern Cape. METHODS: Based at Zithulele Hospital, a health care network between the hospital, 13 clinics, and 50 CHWs has been created. The functions of each tier of care are different and complementary. This article describes the recruitment, training, supervision, monitoring, and outcomes when CHWs who deliver maternal, child health, nutrition and general care through home visits. RESULTS: CHWs, especially in rural settings, can find and refer new TB/HIV cases, ill children and at-risk pregnant women; rehabilitate malnourished children at home; support TB and HIV treatment adherence; treat diarrhoea, worm infestation and skin problems; and, distribute Vitamin A. CHWs provide follow-up after clinic and hospital care, support families to apply health information, problem-solve the health and social challenges of daily living, and assist in accessing social grants. Case examples of how this model functions are provided. CONCLUSION: This generalist CHW home intervention is a potential model for the re-engineering of the primary health care system in South Africa. PMID- 26279950 TI - Current National Approach to Healthcare ICT Standardization: Focus on Progress in New Zealand. AB - OBJECTIVES: Many countries try to efficiently deliver high quality healthcare services at lower and manageable costs where healthcare information and communication technologies (ICT) standardisation may play an important role. New Zealand provides a good model of healthcare ICT standardisation. The purpose of this study was to review the current healthcare ICT standardisation and progress in New Zealand. METHODS: This study reviewed the reports regarding the healthcare ICT standardisation in New Zealand. We also investigated relevant websites related with the healthcare ICT standards, most of which were run by the government. Then, we summarised the governance structure, standardisation processes, and their output regarding the current healthcare ICT standards status of New Zealand. RESULTS: New Zealand government bodies have established a set of healthcare ICT standards and clear guidelines and procedures for healthcare ICT standardisation. Government has actively participated in various enactments of healthcare ICT standards from the inception of ideas to their eventual retirement. Great achievements in eHealth have already been realized, and various standards are currently utilised at all levels of healthcare regionally and nationally. Standard clinical terminologies, such as International Classification of Diseases (ICD) and Systematized Nomenclature of Medicine - Clinical Terms (SNOMED-CT) have been adopted and Health Level Seven (HL7) standards are actively used in health information exchanges. CONCLUSIONS: The government to New Zealand has well organised ICT institutions, guidelines, and regulations, as well as various programs, such as e-Medications and integrated care services. Local district health boards directly running hospitals have effectively adopted various new ICT standards. They might already be benefiting from improved efficiency resulting from healthcare ICT standardisation. PMID- 26279952 TI - Conformance Analysis of Clinical Pathway Using Electronic Health Record Data. AB - OBJECTIVES: The objective of this study was to confirm the conformance rate of the actual usage of the clinical pathway (CP) using Electronic Health Record (EHR) log data in a tertiary general university hospital to improve the CP by reflecting real-world care processes. METHODS: We analyzed the application and matching rates of clinicians' orders with predefined CP order sets based on data from 164 inpatients who received appendectomies out of all patients who were hospitalized from August 2013 to June 2014. We collected EHR log data on patient information, medication orders, operation performed, diagnosis, transfer, and CP order sets. The data were statistically analyzed. RESULTS: The average value of the actual application rate of the prescribed CP order ranged from 0.75 to 0.89. The application rate decreased when the order date was factored in along with the order code and type. Among CP pre-operation, intra-operation, post-operation, routine, and discharge orders, orders pertaining to operations had higher application rates than other types of orders. Routine orders and discharge orders had lower application rates. CONCLUSIONS: This analysis of the application and matching rates of CP orders suggests that it is possible to improve these rates by updating the existing CP order sets for routine discharge orders to reflect data-driven evidence. This study shows that it is possible to improve the application and matching rates of the CP using EHR log data. However, further research should be performed to analyze the effects of these rates on care outcomes. PMID- 26279951 TI - Review of Social and Organizational Issues in Health Information Technology. AB - OBJECTIVES: This paper reviews organizational and social issues (OSIs) in health information technology (HIT). METHODS: A review and synthesis of the literature on OSIs in HIT was conducted. RESULTS: Five overarching themes with respect to OSIs in HIT were identified and discussed: scope and frameworks for defining OSIs in HIT, context matters, process immaturity and complexity, trade-offs will happen and need to be discussed openly, and means of studying OSIs in HIT. CONCLUSIONS: There is a wide body of literature that provides insight into OSIs in HIT, even if many of the studies are not explicitly labelled as such. The two biggest research needs are more explicit and theoretical studies of OSI in HITs and more research on integrating micro and macro perspectives of HIT use in organizations. PMID- 26279953 TI - Data-Mining-Based Coronary Heart Disease Risk Prediction Model Using Fuzzy Logic and Decision Tree. AB - OBJECTIVES: The importance of the prediction of coronary heart disease (CHD) has been recognized in Korea; however, few studies have been conducted in this area. Therefore, it is necessary to develop a method for the prediction and classification of CHD in Koreans. METHODS: A model for CHD prediction must be designed according to rule-based guidelines. In this study, a fuzzy logic and decision tree (classification and regression tree [CART])-driven CHD prediction model was developed for Koreans. Datasets derived from the Korean National Health and Nutrition Examination Survey VI (KNHANES-VI) were utilized to generate the proposed model. RESULTS: The rules were generated using a decision tree technique, and fuzzy logic was applied to overcome problems associated with uncertainty in CHD prediction. CONCLUSIONS: The accuracy and receiver operating characteristic (ROC) curve values of the propose systems were 69.51% and 0.594, proving that the proposed methods were more efficient than other models. PMID- 26279954 TI - Diffusion of Electronic Medical Record Based Public Hospital Information Systems. AB - OBJECTIVES: This study was conducted to evaluate the adoption behavior of a newly developed Electronic Medical Record (EMR)-based information system (IS) at three public hospitals in Korea with a focus on doctors and nurses. METHODS: User satisfaction scores from four performance layers were analyzed before and two times after the newly develop system was introduced to evaluate the adoption process of the IS with Rogers' diffusion theory. RESULTS: The 'intention to use' scores, the most important indicator for determining whether or not to adopt the IS in Rogers' confirmation stage for doctors, were very high in the third survey (4.21). In addition, the scores for 'reduced medication errors', which is the key indicator for evaluating the success of the IS, increased in the third survey for both doctors and nurses. The factors influencing 'intention to use' with a high odds ratio (>1.5) were the 'frequency of attendance of user training sessions', 'mandatory use of system', 'reduced medication errors', and 'reduced medical record documentation time' for both doctors and nurses. CONCLUSIONS: These findings show that the new EMR-based IS was well accepted by doctors. Both doctors and nurses also positively considered the effects of the new IS on their clinical environments. PMID- 26279955 TI - Healthcare Utilization Monitoring System in Korea. AB - OBJECTIVES: It is important to monitor the healthcare utilization of patients at the national level to make evidence-based policy decisions and manage the nation's healthcare sector. The Health Insurance Review & Assessment Service (HIRA) has run a Healthcare Utilization Monitoring System (HUMS) since 2008. The objective of this paper is to introduce HIRA's HUMS. METHODS: This study described the HUMS's system structure, capacity, functionalities, and output formats run by HIRA in the Republic of Korea. Regarding output formats, this study extracted diabetes related health insurance claims through the HUMS from August 1, 2014 to May 31, 2015. RESULTS: The HUMS has kept records of health insurance claim data for 4 years. It has a 14-terabyte hardware capacity and employs several easy-to-use programs for maintenance of the system, such as MSTR, SAS, etc. Regarding functionalities, users should input diseases codes, target periods, facility types, and types of attributes, such as the number of healthcare utilizations or healthcare costs. It also has a functionality to predict healthcare utilization and costs. When this study extracted diabetes related data, it was found that the trend of healthcare costs for the treatment of diabetes and the number of patients with diabetes were increasing. CONCLUSIONS: HIRA's HUMS works well to monitor healthcare utilization of patients at the national level. The HUMS has a high-capacity hardware infrastructure and several operational programs that allows easy access to summaries as well as details to identify contributing factors for abnormality, but it has a limitation in that there is often a time lag between the provision of healthcare to patients and the filing of health claims. PMID- 26279956 TI - Usability of Academic Electronic Medical Record Application for Nursing Students' Clinical Practicum. AB - OBJECTIVES: Nursing curricula for undergraduate nursing students need to reflect the information technology used in current nursing practice. A smart-device Academic Electronic Medical Record (AEMR) application can help nursing students access and document records for the clinical practicum. We conducted a pilot study to evaluate the usability of an AEMR application before applying it to the clinical nursing practicum. METHODS: A previously developed EMR application was modified as an AEMR to access patient information at bedside and to practice documentation. We added several features to the current EMR application to create an AEMR environment. We created a series of document forms and several useful scales on an external application, which included nursing admission notes, vital signs, and intake/output. The case scenarios and tasks were created by a research team to evaluate aspects of AEMRs, including their usability and functionality. Five nursing students completed 15 tasks using a think-aloud method with a tablet device. RESULTS: Minor usability issues were identified and rectified. All participants indicated that they became familiar with the application with little effort. They said that the application icons were intuitive, which helped them find patient information more quickly and accurately. CONCLUSIONS: The application will improve timely access to patient data and documentation for nursing students. We are confident that this AEMR application will enhance nursing students' experience with their clinical practicum, and help them to better understand patient conditions and document them with ideal accessibility. PMID- 26279957 TI - Application of Telemedicine System to Prehospital Medical Control. AB - OBJECTIVES: Although ambulance-based telemedicine has been reported to be safe and feasible, its clinical usefulness has not been well documented, and different prehospital management systems would yield different results. The authors evaluated the feasibility and usefulness of telemedicine-assisted direct medical control in the Korean emergency medical service system. METHODS: Twenty ambulances in the Busan area were equipped with a telemedicine system. Three-lead electrocardiogram, blood pressure, and pulse oximetry data from the patient and audiovisual input from the scene were transferred to a server. Consulting physicians used desktop computers and the internet to connect to the server. Both requesting emergency medical service (EMS) providers and consulting physicians were asked to fill out report forms and submit them for analysis. RESULTS: In the 41 cases in which telemedicine equipment was used, cellular phones were concomitantly used in 28 cases (68.35%) to compensate for the poor audio quality provided by the equipment. The EMS providers rated the video transmission quality with a 4-point average score (interquartile range [IQR] 2-5) on a 5-point scale, and they rated the biosignal transmission quality as 4 (IQR 3-5). The consulting physicians rated the video quality as 4 (IQR 2.5-4) and the biosignal quality as 4 (IQR 3-4). The physicians' ratings for usefulness for making diagnosis or treatment decisions did not differ significantly in relation to the method of communication used. CONCLUSIONS: Our study did not find any significant advantage of implementing telemedicine over the use of voice calls in delivering on-line medical control. More user-friendly, smaller devices with clear advantages over voice communication would be required before telemedicine can be successfully implemented in prehospital patient care. PMID- 26279958 TI - Clinical Application of Solid Model Based on Trabecular Tibia Bone CT Images Created by 3D Printer. AB - OBJECTIVES: The aim of this work is to use a 3D solid model to predict the mechanical loads of human bone fracture risk associated with bone disease conditions according to biomechanical engineering parameters. METHODS: We used special image processing tools for image segmentation and three-dimensional (3D) reconstruction to generate meshes, which are necessary for the production of a solid model with a 3D printer from computed tomography (CT) images of the human tibia's trabecular and cortical bones. We examined the defects of the mechanism for the tibia's trabecular bones. RESULTS: Image processing tools and segmentation techniques were used to analyze bone structures and produce a solid model with a 3D printer. CONCLUSIONS: These days, bio-imaging (CT and magnetic resonance imaging) devices are able to display and reconstruct 3D anatomical details, and diagnostics are becoming increasingly vital to the quality of patient treatment planning and clinical treatment. Furthermore, radiographic images are being used to study biomechanical systems with several aims, namely, to describe and simulate the mechanical behavior of certain anatomical systems, to analyze pathological bone conditions, to study tissues structure and properties, and to create a solid model using a 3D printer to support surgical planning and reduce experimental costs. These days, research using image processing tools and segmentation techniques to analyze bone structures to produce a solid model with a 3D printer is rapidly becoming very important. PMID- 26279959 TI - Correction: Effects of Health Information Technology on Malpractice Insurance Premiums. AB - [This corrects the article on p. 118 in vol. 21, PMID: 25995964.]. PMID- 26279960 TI - Continuous Shape Estimation of Continuum Robots Using X-ray Images. AB - We present a new method for continuously and accurately estimating the shape of a continuum robot during a medical procedure using a small number of X-ray projection images (e.g., radiographs or fluoroscopy images). Continuum robots have curvilinear structure, enabling them to maneuver through constrained spaces by bending around obstacles. Accurately estimating the robot's shape continuously over time is crucial for the success of procedures that require avoidance of anatomical obstacles and sensitive tissues. Online shape estimation of a continuum robot is complicated by uncertainty in its kinematic model, movement of the robot during the procedure, noise in X-ray images, and the clinical need to minimize the number of X-ray images acquired. Our new method integrates kinematics models of the robot with data extracted from an optimally selected set of X-ray projection images. Our method represents the shape of the continuum robot over time as a deformable surface which can be described as a linear combination of time and space basis functions. We take advantage of probabilistic priors and numeric optimization to select optimal camera configurations, thus minimizing the expected shape estimation error. We evaluate our method using simulated concentric tube robot procedures and demonstrate that obtaining between 3 and 10 images from viewpoints selected by our method enables online shape estimation with errors significantly lower than using the kinematic model alone or using randomly spaced viewpoints. PMID- 26279961 TI - Use of Pearson's Chi-Square for Testing Equality of Percentile Profiles across Multiple Populations. AB - In large sample studies where distributions may be skewed and not readily transformed to symmetry, it may be of greater interest to compare different distributions in terms of percentiles rather than means. For example, it may be more informative to compare two or more populations with respect to their within population distributions by testing the hypothesis that their corresponding respective 10th, 50th, and 90th percentiles are equal. As a generalization of the median test, the proposed test statistic is asymptotically distributed as Chi square with degrees of freedom dependent upon the number of percentiles tested and constraints of the null hypothesis. Results from simulation studies are used to validate the nominal 0.05 significance level under the null hypothesis, and asymptotic power properties that are suitable for testing equality of percentile profiles against selected profile discrepancies for a variety of underlying distributions. A pragmatic example is provided to illustrate the comparison of the percentile profiles for four body mass index distributions. PMID- 26279962 TI - Lemierre's Syndrome Caused by Klebsiella pneumoniae in a Diabetic Patient: A Case Report and Review of the Literature. AB - Lemierre's syndrome is characterized by an oropharyngeal infection with internal jugular vein thrombosis followed by metastatic infections in other organs. This infection is usually caused by Fusobacterium spp. In this report, we present a rare case of Klebsiella pneumoniae-associated Lemierre's syndrome in a patient with poorly-controlled diabetes mellitus. The infection was complicated by septic emboli in many organs, which led to the patient's death, despite combined antibiotics, anticoagulant therapy, and surgical intervention. Therein, a literature review was performed for reported cases of Lemierre's syndrome caused by Klebsiella pneumoniae and the results are summarized here. PMID- 26279963 TI - Improving the Utilization of Human Papillomavirus and Cervical Cytology Co testing for Cervical Cancer Screening in an Obstetrics and Gynecology Resident Clinic. AB - Human Papillomavirus (HPV) testing in combination with cervical cytology (HPV co testing) has been recommended for cervical cancer screening for women 30 to 65 years of age. In several studies, HPV co-testing increased sensitivity for detecting high grade dysplasia and resulted in cost-savings. This retrospective cohort study assessed the prevalence of HPV co-testing in an obstetrics and gynecology resident clinic before and after a brief educational intervention which was designed to reinforce current cervical cancer screening recommendations. The intervention consisted of a short presentation that was given to all residents and medical assistants in October 2011. The proportion of women age 30-65 years of age who had cervical cancer screening with HPV co testing as compared to cervical cytology alone was compared before and after the intervention using chi-square tests. The goal of the intervention was to increase the percentage of patients receiving co-testing from 0.5% to 7.8%. Each arm (pre- and post-intervention) required 130 subjects to achieve 80% power with a significance of P = .05. No significant differences in demographics including age, insurance type, and cytology were noted. HPV co-testing increased from 0% to 55% (P < .001). Of the 72 subjects who had co-testing, 58 (80%) will not need cervical cancer screening for another 5 years. HPV co-testing represents an underutilized cervical cancer screening modality for women 30 years and older. This brief educational intervention, adaptable to any clinical setting, significatnly increased co-testing at the clinical site. PMID- 26279964 TI - Autoimmune Hepatitis in Hawai'i. AB - Autoimmune Hepatitis (AIH) is a poorly understood disease. There has been a paucity of reports on the epidemiology and clinical course of AIH in multiethnic populations. The aim of this study is to examine the clinical and serologic features of AIH in the multiethnic population of Hawai'i. This was a retrospective, cross-sectional study of a cohort of patients seen between 2010 2013 in a tertiary referral center in Hawai'i. All 32 patients were diagnosed according to International Autoimmune Hepatitis Group (IAIHG) criteria. The mean (SD) age of diagnosis was 49.4 (17.5) years, 75% of patients were female, 72% were Asian, 19% were Caucasian, 6% were Pacific Islander, and 3% were African American. When compared to Caucasians, Asians had lower transaminase levels and international normalized ratio (INR), and were more likely to have anti-nuclear antibody (ANA) seropositivity at presentation. Asians were also older at diagnosis and more likely to achieve complete or partial remission. Patients diagnosed before the age of 40 had higher levels of total bilirubin at presentation compared to those diagnosed after the age of 40. No significant differences were observed between genders. Asian patients with type I AIH present later in life with more favorable laboratory values, and have a superior treatment response compared to Caucasians. Diagnosis before the age of 40 is associated with less favorable laboratory values at diagnosis. Further studies are necessary to validate these findings and determine the reason for the ethnic differences. PMID- 26279965 TI - Medical School Hotline: Celebrating 15 Years of the Area Health Education Center at the John A. Burns School of Medicine. PMID- 26279966 TI - Insights in Public Health: Protecting Public Health Through Governmental Transparency: How the Hawai'i Department of Health's New "Stoplight" Placarding Program is Attempting to Influence Behavioral Change in Hawai'i's Food Industry. AB - Reducing the occurrence of and influencing the rapid correction of food illness risk factors is a common goal for all governmental food regulatory programs nationwide. Foodborne illness in the United States is a major cause of personal distress, preventable illness, and death. To improve public health outcomes, additional workforce was required due to long standing staffing shortages and was obtained partially through consolidation of the Hawai'i Department of Health's (HDOH) two food safety programs, the Sanitation Branch, and the Food & Drug Branch in July 2012, and through legislation that amended existing statutes governing the use of food establishment permit fees. Additionally, a more transparent food establishment grading system was developed after extensive work with industry partners based on three possible placards issued after routine inspections: green, yellow, and red. From late July 2014 to May 2015, there were 6,559 food establishments inspected statewide using the placard system with 79% receiving a green, 21% receiving a yellow, and no red placards issued. Sufficient workforce to allow timely inspections, continued governmental transparency, and use of new technologies are important to improve food safety for the public. PMID- 26279968 TI - Expression of synaptophysin protein in different dopaminergic cell lines. AB - Synaptophysin is a specific presynaptic marker for neurons. Loss of synaptophysin occurs in Parkinson's disease, dementia with Lewy bodies and other neurodegenerative diseases. In vitro studies on synaptophysin are important to understand both the function of the protein itself and its implication in the pathogenesis of neurological diseases. In this study, we determined synaptophysin protein expression by Western analysis in 6 different dopaminergic cell lines including one human (SH-SY5Y), two rat (PC12 and N27) and 3 mouse (MN9D, Cath.a and CAD) cell lines. We found that synaptophysin protein is richly expressed in PC12 cells, but much less in other cells we studied. The order of synaptophysin expression from high to low for the other 5 cell lines was CAD> SH-SY5Y> MN9D> Cath.a = N27 cells, with Cath.a and N27 cells expressing almost undetectable content of synaptophysin protein. These data may be useful to other researchers in choosing a dopaminergic cell line as a model system to study the pathophysiology of neuron terminal loss. PMID- 26279969 TI - Histoplasmosis infections worldwide: thinking outside of the Ohio River valley. AB - In the United States, histoplasmosis is generally thought to occur mainly in the Ohio and Mississippi River Valleys, and the classic map of histoplasmosis distribution reflecting this is second nature to many U.S. physicians. With the advent of the HIV pandemic reports of patients with progressive disseminated histoplasmosis and AIDS came from regions of known endemicity, as well as from regions not thought to be endemic for histoplasmosis throughout the world. In addition, our expanding armamentarium of immunosuppressive medications and biologics has increased the diagnosis of histoplasmosis worldwide. While our knowledge of areas in which histoplasmosis is endemic has improved, it is still incomplete. Our contention is that physicians should consider histoplasmosis with the right constellations of symptoms in any febrile patient with immune suppression, regardless of geographic location or travel history. PMID- 26279970 TI - Cryptococcal Meningitis: Diagnosis and Management Update. AB - Recent advances in the diagnosis and management of cryptococcal meningitis are promising and have been improving long-term survival. Point of care testing has made diagnosing cryptococcal meningitis rapid, practical, and affordable. Targeted screening and treatment programs for cryptococcal antigenemia are a cost effective method for reducing early mortality on antiretroviral therapy (ART). Optimal initial management with amphotericin and flucytosine improves survival against alternative therapies, although amphotericin is difficult to administer and flucytosine is not available in middle or low income countries, where cryptococcal meningitis is most prevalent. Controlling increased intracranial pressure with serial therapeutic lumbar punctures has a proven survival benefit. Delaying ART initiation for 4 weeks after the diagnosis of cryptococcal meningitis is associated with improved survival. Fortunately, new approaches have been leading the way toward improving care for cryptococcal meningitis patients. New trials utilizing different combinations of antifungal therapy are reviewed, and we summarize the efficacy of different regimens. PMID- 26279971 TI - Systemic and Mucosal Immune Responses to Cryptosporidium-Vaccine Development. AB - Cryptosporidium spp is a major cause of diarrheal disease worldwide, particularly in malnourished children and untreated AIDS patients in developing countries in whom it can cause severe, chronic and debilitating disease. Unfortunately, there is no consistently effective drug for these vulnerable populations and no vaccine, partly due to a limited understanding of both the parasite and the host immune response. In this review, we will discuss our current understanding of the systemic and mucosal immune responses to Cryptosporidium infection, discuss the feasibility of developing a Cryptosporidium vaccine and evaluate recent advances in Cryptosporidium vaccine development strategies. PMID- 26279972 TI - Recent Patents Pertaining to Immune Modulation and Musculoskeletal Regeneration with Wharton's Jelly Cells. AB - Umbilical cord mesenchymal stromal cells (UCMSCs) are isolated from Wharton's jelly in the umbilical cord at birth, and offer advantages over adult mesenchymal stromal cells (MSCs) such as highly efficient isolation, faster proliferation in vitro, a broader differentiation potential, and non-invasive harvesting procedure. Their expansion and differentiation potential renders them a promising cell source for tissue engineering and clinical applications. This review discusses recent updates on the differentiation strategies for musculoskeletal tissue engineering including cartilage, bone, and muscle. In addition to tissue engineering applications, UCMSCs can be utilized to support hematopoiesis and modulate immune response. We review the patents relevant to the application of MSCs including UCMSCs in hematopoiesis and immune modulation. Finally, the current hurdles in the clinical translation of UCMSCs are discussed. During clinical translation, it is critical to develop large-scale manufacturing of UCMSCs as well as the composition of expansion and differentiation media. Four clinical trials to date have examined the safety and efficacy of UCMSCs. Once public banking of UCMSCs is available to supply matched allogeneic units and once UCMSC manufacturing is standardized, we anticipate that UCMSCs will be more widely used in clinical trials. PMID- 26279973 TI - A Longitudinal Analysis of the Effects of Socioeconomic Factors, Foreign Media, and Attitude toward Appearance on General and Central Adiposity in Chinese Adolescents. AB - OBJECTIVE: This paper explores the longitudinal effects of socioeconomic factors (i.e., parent education and family income level), foreign media, and attitude toward appearance on general and central adiposity among Chinese adolescents. METHOD: A longitudinal analysis was performed using data from the China Seven Cities Study, a health promotion and smoking prevention study conducted in seven cities across Mainland China between 2002 and 2005. Participants included 5,020 middle and high school students and their parents. Explanatory variables included foreign media exposure, attitude toward appearance, parent education, and family income. Three-level, random-effect models were used to predict general adiposity (i.e., body mass index) and central adiposity (i.e., waist circumference). The Generalized Estimating Equation approach was utilized to determine the effect of explanatory variables on overweight status. RESULTS: Among girls, foreign media exposure was significantly negatively associated with general adiposity over time (beta=-0.06, p=0.01 for middle school girls; beta=-0.06, p=0.03 for high school girls). Attitude toward appearance was associated with lesser odds of being overweight, particularly among high school girls (OR=0.86, p<0.01). Among boys, parental education was significantly positively associated with general adiposity (beta=0.62, p<0.01 for middle school boys; beta=0.37, p=0.02 for high school boys) and associated with greater odds of being overweight (OR=1.55, p<0.01 for middle school boys; OR=1.26, p=0.04 for high school boys). Across all gender and grade levels, family income was significantly negatively associated with central adiposity over time. CONCLUSION: Interventions addressing Chinese adolescent overweight/obesity should consider these factors as potential focus areas. PMID- 26279974 TI - New p-Substituted Salicylaldehyde Phenylhydrazone Derivatives: Synthesis, Characterization, and Antioxidant Activities. AB - A series of new p-nitrophenylhydrazone derivatives 3a-f were synthesized, characterized, and investigated for their antioxidant activities. These compounds have been synthesized by refluxing (p-nitrophenyl)hydrazine with 4-sub-stituted salicylaldehydes. The structures of the compounds were established by IR, (1)H- and (13)C-NMR, and MS data. The antioxidant activities (free radical-scavenging activity, reducing power, metal chelating activity, and total anti-oxidant activity) of the hydrazone compounds were evaluated. All of the compounds exhibited significant activities, while compound 3a, with the shortest chain, showed the highest antioxidant activity in all of the tests. PMID- 26279975 TI - Stability-Indicating RP-HPLC Method for the Determination of Ambrisentan and Tadalafil in Pharmaceutical Dosage Form. AB - A simple, rapid, and highly selective RP-HPLC method was developed for the simultaneous determination of Ambrisentan (AMB) and Tadalafil (TADA) drug substances in the fixed dosage strength of 10 mg and 40 mg, respectively. Effective chromatographic separation was achieved using a Hypersil GOLD C18 column (150 mm * 4.6 mm internal diameter, 5 MUm particle size) with a mobile phase composed of methanol, water, and acetonitrile in the ratio of 40:40:20 (by volume). The mobile phase was pumped using a gradient HPLC system at a flow rate of 0.5 mL/min, and quantification of the analytes was based on measuring their peak areas at 260 nm. The retention times for Ambrisentan and Tadalafil were about 2.80 and 7.10 min, respectively. The reliability and analytical performance of the proposed HPLC procedure were statistically validated with respect to system suitability, linearity, ranges, precision, accuracy, specificity, robustness, detection, and quantification limits. Calibration curves were linear in the ranges of 1-20 MUg/mL for Ambrisentan and 4-80 MUg/mL for Tadalafil with correlation coefficients >0.990. The proposed method proved to be selective and stability-indicating by the resolution of the two analytes from the forced degradation (hydrolysis, oxidation, and photolysis) products. The validated HPLC method was successfully applied to the analysis of AMB and TADA in pharmaceutical dosage form. PMID- 26279976 TI - Low Density Lipid Nanoparticles for Solid Tumor Targeting. AB - One of the most significant characteristics of cancer cells is their rapid dividing ability and overexpression of LDL receptors, which offers an opportunity for the selective targeting of these cells. 5-Fluorouracil (5-FU)-encapsulated low density lipid nanoparticles (LDLN) were prepared by the emulsion congealing method which mimics the plasma-derived LDL by acquiring the apolipoprotein B-100 from the blood. The average particle size, transmission electron microscope (TEM), and drug content of the prepared LDLN dispersion were found to be 161+/ 3.5 nm, with spherical shape, and 0.370+/-0.05 mg/mL, respectively. In vitro release studies revealed a sustained profile which decreased with a lapse of time. In vivo studies of 5-FU serum concentration and biodistribution revealed a 5-FU serum concentration of 8.5% in tumor cells and about 2.1% in the liver at the end of 24 hr from LDLN. Tumor growth suppression studies showed 185.42% average tumor growth and 89.76% tumor height as compared to the control exhibiting tumor growth at 1166.47% and tumor height at 176.07%. On the basis of these collective data, it is suggested that a higher accumulation of LDLN, when given as an IV, in solid tumors is attributed to the active uptake of LDLN via LDL receptors via apolipoprotein B-100. PMID- 26279977 TI - Novel antigen delivery systems. AB - Vaccines represent the most relevant contribution of immunology to human health. However, despite the remarkable success achieved in the past years, many vaccines are still missing in order to fight important human pathologies and to prevent emerging and re-emerging diseases. For these pathogens the known strategies for making vaccines have been unsuccessful and thus, new avenues should be investigated to overcome the failure of clinical trials and other important issues including safety concerns related to live vaccines or viral vectors, the weak immunogenicity of subunit vaccines and side effects associated with the use of adjuvants. A major hurdle of developing successful and effective vaccines is to design antigen delivery systems in such a way that optimizes antigen presentation and induces broad protective immune responses. Recent advances in vector delivery technologies, immunology, vaccinology and system biology, have led to a deeper understanding of the molecular and cellular mechanisms by which vaccines should stimulate both arms of the adaptive immune responses, offering new strategies of vaccinations. This review is an update of current strategies with respect to live attenuated and inactivated vaccines, DNA vaccines, viral vectors, lipid-based carrier systems such as liposomes and virosomes as well as polymeric nanoparticle vaccines and virus-like particles. In addition, this article will describe our work on a versatile and immunogenic delivery system which we have studied in the past decade and which is derived from a non pathogenic prokaryotic organism: the "E2 scaffold" of the pyruvate dehydrogenase complex from Geobacillus stearothermophilus. PMID- 26279978 TI - Can antiretroviral therapy be tailored to each human immunodeficiency virus infected individual? Role of pharmacogenomics. AB - Pharmacogenetics refers to the effect of single nucleotide polymorphisms (SNPs) within human genes on drug therapy outcome. Its study might help clinicians to increase the efficacy of antiretroviral drugs by improving their pharmacokinetics and pharmacodynamics and by decreasing their side effects. HLAB*5701 genotyping to avoid the abacavir-associated hypersensitivity reaction (HSR) is a cost effective diagnostic tool, with a 100% of negative predictive value, and, therefore, it has been included in the guidelines for treatment of human immunodeficiency virus (HIV) infection. HALDRB*0101 associates with nevirapine induced HSR. CYP2B6 SNPs modify efavirenz plasma levels and their genotyping help decreasing its central nervous system, hepatic and HSR toxicities. Cytokines SNPs might influence the development of drug-associated lipodystrophy. APOA5, APOB, APOC3 and APOE SNPs modify lipids plasma levels and might influence the coronary artery disease risk of HIV-infected individuals receiving antiretroviral therapy. UGT1A1*28 and ABCB1 (MDR1) 3435C > T SNPs modify atazanavir plasma levels and enhance hyperbilirubinemia. Much more effort needs to be still devoted to complete large prospective studies with multiple SNPs genotyping in order to reveal more clues about the role played by host genetics in antiretroviral drug efficacy and toxicity. PMID- 26279980 TI - Middle-East respiratory syndrome coronavirus: Is it worth a world panic? AB - In 2012 Middle-East respiratory syndrome coronavirus (MERS-CoV) was evolved in the Arabian Peninsula. Tremendous and successful efforts have been conducted to discover the genome structure, epidemiology, clinical signs, pathogenesis, diagnosis and antiviral therapy. Taphozous perforatus bats are the incriminated reservoir host and camels are the currently confirmed animal linker. The virus resulted in less than 1000 infected cases and 355 deaths. The case fatality rate of the MERS-CoV is high, however, many survivors of MERS-CoV infection showed inapparent infections and, in several cases, multiple co-infecting agents did exist. Although MERS-CoV appears to be a dangerous disease, it is argued here that a full assessment of current knowledge about the disease does not suggest that it is a truly scary killer. PMID- 26279979 TI - Is the use of IL28B genotype justified in the era of interferon-free treatments for hepatitis C? AB - In 2009, several groups reported that interleukin-28B (IL28B) genotypes are associated with the response to peginterferon plus ribavirin therapy for chronic hepatitis C virus (HCV) infection in a genome-wide association study, although the mechanism of this association is not yet well understood. However, in recent years, tremendous progress has been made in the treatment of HCV infection. In Japan, some patients infected with HCV have the IL28B major genotype, which may indicate a favorable response to interferon-including regimens; however, certain patients within this group are also interferon-intolerant or ineligible. In Japan, interferon-free 24-wk regimens of asunaprevir and daclatasvir are now available for HCV genotype 1b-infected patients who are interferon-intolerant or ineligible or previous treatment null-responders. The treatment response to interferon-free regimens appears better, regardless of IL28B genotype. Maybe other interferon-free regimens will widely be available soon. In conclusion, although some HCV-infected individuals have IL28B favorable alleles, importance of IL28B will be reduced with availability of oral interferon free regimen. PMID- 26279981 TI - Prion-induced neurotoxicity: Possible role for cell cycle activity and DNA damage response. AB - Protein misfolding neurodegenerative diseases arise through neurotoxicity induced by aggregation of host proteins. These conditions include Alzheimer's disease, Huntington's disease, Parkinson's disease, motor neuron disease, tauopathies and prion diseases. Collectively, these conditions are a challenge to society because of the increasing aged population and through the real threat to human food security by animal prion diseases. It is therefore important to understand the cellular and molecular mechanisms that underlie protein misfolding-induced neurotoxicity as this will form the basis for designing strategies to alleviate their burden. Prion diseases are an important paradigm for neurodegenerative conditions in general since several of these maladies have now been shown to display prion-like phenomena. Increasingly, cell cycle activity and the DNA damage response are recognised as cellular events that participate in the neurotoxic process of various neurodegenerative diseases, and their associated animal models, which suggests they are truly involved in the pathogenic process and are not merely epiphenomena. Here we review the role of cell cycle activity and the DNA damage response in neurodegeneration associated with protein misfolding diseases, and suggest that these events contribute towards prion induced neurotoxicity. In doing so, we highlight PrP transgenic Drosophila as a tractable model for the genetic analysis of transmissible mammalian prion disease. PMID- 26279982 TI - Pharmacogenetics as a tool to tailor antiretroviral therapy: A review. AB - Highly active antiretroviral therapy (HAART) has substantially changed human immunodeficiency virus (HIV) infection from an inexorably fatal condition into a chronic disease with a longer life expectancy. This means that HIV patients should receive antiretroviral drugs lifelong, and the problems concerning with a chronic treatment (tolerability, side effects, adherence to treatment) have now become dominant. In this context, strategies for the treatment personalization have taken a central role in optimizing the therapeutic response and prevention of adverse drug reactions. In this setting, the study of pharmacogenetics features could be a very useful tool in clinical practice; moreover, nowadays the study of genetic profiles allows optimizations in the therapeutic management of People Living With HIV (PLWH) through the use of test introduced into clinical practice and approved by international guidelines for the adverse effects prevention such as the genetic test HLA-B*5701 to detect hypersensitivity to Abacavir. For other tests further studies are needed: CYP2B6 516 G > T testing may be able to identify patients at higher risk of Central Nervous System side effects following standard dosing of Efavirenz, UGT1A1*28 testing before initiation of antiretroviral therapy containing Atazanavir may aid in identifying individuals at risk of hyperbilirubinaemia. Pharmacogenetics represents a research area with great growth potential which may be useful to guide the rational use of antiretrovirals. PMID- 26279983 TI - Non-AIDS definings malignancies among human immunodeficiency virus-positive subjects: Epidemiology and outcome after two decades of HAART era. AB - Highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV) infection has been widely available in industrialized countries since 1996; its widespread use determined a dramatic decline in acquired immunodeficiency syndrome (AIDS)-related mortality, and consequently, a significant decrease of AIDS-defining cancers. However the increased mean age of HIV-infected patients, prolonged exposure to environmental and lifestyle cancer risk factors, and coinfection with oncogenic viruses contributed to the emergence of other malignancies that are considered non-AIDS-defining cancers (NADCs) as a relevant fraction of morbidity and mortality among HIV-infected people twenty years after HAART introduction. The role of immunosuppression in the pathogenesis of NADCs is not well defined, and future researches should investigate the etiology of NADCs. In the last years there is a growing evidence that intensive chemotherapy regimens and radiotherapy could be safely administrated to HIV-positive patients while continuing HAART. This requires a multidisciplinary approach and a close co operation of oncologists and HIV-physicians in order to best manage compliance of patients to treatment and to face drug-related side effects. Here we review the main epidemiological features, risk factors and clinical behavior of the more common NADCs, such as lung cancer, hepatocellular carcinoma, colorectal cancer and anal cancer, Hodgkin's lymphoma and some cutaneous malignancies, focusing also on the current therapeutic approaches and preventive screening strategies. PMID- 26279985 TI - Women's willingness to be tested for human immunodeficiency virus during pregnancy: A review. AB - Mother-to-child-transmission of human immunodeficiency virus (HIV) is a primary cause of pediatric infections with HIV. Many of these infections involve women who were not tested early enough in pregnancy, or who did not receive prevention services. HIV testing of pregnant women is considered to be one of the key strategies for preventing mother-to-child-transmission of HIV, but HIV testing rates among pregnant women in various countries remain suboptimal. Understanding the factors relating to women's willingness to be tested for HIV during pregnancy is critical for developing strategies to increase HIV testing rates among pregnant women. Extensive research points to various factors relating to women's willingness to be tested for HIV during pregnancy, and various recommendations aimed at improving testing rates among pregnant women have been suggested based on the research. In light of the goals set by the United Nations to reduce the rate of infants infected with HIV, it is necessary to summarize what is currently known regarding factors related to women's willingness to be tested for HIV during pregnancy. The purpose of this review is therefore to examine factors related to women's willingness to be tested for HIV during pregnancy, and to summarize recommendations for practice and further research. PMID- 26279986 TI - Insights into human immunodeficiency virus-hepatitis B virus co-infection in India. AB - Shared routes of transmission lead to frequent human immunodeficiency virus (HIV) hepatitis B virus (HBV) co-infection in a host which results in about 10% of HIV positive individuals to have chronic hepatitis B infection worldwide. In post antiretroviral therapy era, liver diseases have emerged as the leading cause of morbidity and mortality in HIV-infected individuals and HBV co-infection have become the major health issue among this population particularly from the regions with endemic HBV infection. In setting of HIV-HBV co-infection, HIV significantly impacts the natural history of HBV infection, its disease profile and the treatment outcome in negative manner. Moreover, the epidemiological pattern of HBV infection and the diversity in HBV genome (genotypic and phenotypic) are also varied in HIV co-infected subjects as compared to HBV mono-infected individuals. Several reports on the abovementioned issues are available from developed parts of the world as well as from sub-Saharan African countries. In contrast, most of these research areas remained unexplored in India despite having considerable burden of HIV and HBV infections. This review discusses present knowledge from the studies on HIV-HBV co-infection in India and relevant reports from different parts of the world. Issues needed for the future research relevant to HIV-HBV co infection in India are also highlighted here, including a call for further investigations on this field of study. PMID- 26279984 TI - Post-transcriptional gene silencing, transcriptional gene silencing and human immunodeficiency virus. AB - While human immunodeficiency virus 1 (HIV-1) infection is controlled through continuous, life-long use of a combination of drugs targeting different steps of the virus cycle, HIV-1 is never completely eradicated from the body. Despite decades of research there is still no effective vaccine to prevent HIV-1 infection. Therefore, the possibility of an RNA interference (RNAi)-based cure has become an increasingly explored approach. Endogenous gene expression is controlled at both, transcriptional and post-transcriptional levels by non-coding RNAs, which act through diverse molecular mechanisms including RNAi. RNAi has the potential to control the turning on/off of specific genes through transcriptional gene silencing (TGS), as well as fine-tuning their expression through post transcriptional gene silencing (PTGS). In this review we will describe in detail the canonical RNAi pathways for PTGS and TGS, the relationship of TGS with other silencing mechanisms and will discuss a variety of approaches developed to suppress HIV-1 via manipulation of RNAi. We will briefly compare RNAi strategies against other approaches developed to target the virus, highlighting their potential to overcome the major obstacle to finding a cure, which is the specific targeting of the HIV-1 reservoir within latently infected cells. PMID- 26279987 TI - Next-generation sequencing in clinical virology: Discovery of new viruses. AB - Viruses are a cause of significant health problem worldwide, especially in the developing nations. Due to different anthropological activities, human populations are exposed to different viral pathogens, many of which emerge as outbreaks. In such situations, discovery of novel viruses is utmost important for deciding prevention and treatment strategies. Since last century, a number of different virus discovery methods, based on cell culture inoculation, sequence independent PCR have been used for identification of a variety of viruses. However, the recent emergence and commercial availability of next-generation sequencers (NGS) has entirely changed the field of virus discovery. These massively parallel sequencing platforms can sequence a mixture of genetic materials from a very heterogeneous mix, with high sensitivity. Moreover, these platforms work in a sequence-independent manner, making them ideal tools for virus discovery. However, for their application in clinics, sample preparation or enrichment is necessary to detect low abundance virus populations. A number of techniques have also been developed for enrichment or viral nucleic acids. In this manuscript, we review the evolution of sequencing; NGS technologies available today as well as widely used virus enrichment technologies. We also discuss the challenges associated with their applications in the clinical virus discovery. PMID- 26279988 TI - Perinatally infected adolescents living with human immunodeficiency virus (perinatally human immunodeficiency virus). AB - The availability of highly potent antiretroviral treatment during the last decades has transformed human immunodeficiency virus (HIV) infection into a chronic disease. Children that were diagnosed during the first months or years of life and received treatment, are living longer and better and are presently reaching adolescence and adulthood. Perinatally HIV-infected adolescents (PHIV) and young adults may present specific clinical, behavior and social characteristics and demands. We have performed a literature review about different aspects that have to be considered in the care and follow-up of PHIV. The search included papers in the MEDLINE database via PubMed, located using the keywords "perinatally HIV-infected" AND "adolescents". Only articles published in English or Portuguese from 2003 to 2014 were selected. The types of articles included original research, systematic reviews, and quantitative or qualitative studies; case reports and case series were excluded. Results are presented in the following topics: "Puberal development and sexual maturation", "Growth in weight and height", "Bone metabolism during adolescence", "Metabolic complications", "Brain development, cognition and mental health", "Reproductive health", "Viral drug resistance" and "Transition to adult outpatient care". We hope that this review will support the work of pediatricians, clinicians and infectious diseases specialists that are receiving these subjects to continue treatment. PMID- 26279989 TI - Purinergic signaling and human immunodeficiency virus/acquired immune deficiency syndrome: From viral entry to therapy. AB - Human immunodeficiency virus (HIV) infection is a serious condition associated to severe immune dysfunction and immunodeficiency. Mechanisms involved in HIV associated immune activation, inflammation and loss of CD4+ T cells have been extensively studied, including those concerning purinergic signaling pathways. Purinergic signaling components are involved in viral entry and replication and disease progression. Research involving the participation of purinergic signaling in HIV infection has been not only important to elucidate disease mechanisms but also to introduce new approaches to therapy. The involvement of purinergic signaling in the pathogenesis of HIV infection and its implications in the control of the HIV infection are reviewed in this paper. PMID- 26279991 TI - Associations among depression, suicidal behavior, and quality of life in patients with human immunodeficiency virus. AB - AIM: To investigate the potential associations among major depression, quality of life, and suicidal behavior in human immunodeficiency virus (HIV) patients. METHODS: A detailed MEDLINE search was carried out to identify all articles and book chapters in English published from January 1995 to January 2015. RESULTS: Based on the main findings, the prevalence of major depressive disorder (MDD) ranged from 14.0% to 27.2%. Furthermore, the prevalence of suicidal ideation varied from 13.6% to 31.0% whereas, attempted suicides were reported to range from 3.9% to 32.7%. Interestingly, various associated risk factors for both depression and suicide were identified in HIV patients. Finally, consistent associations were reported among MDD, suicidal ideation, and poor quality of life in individuals living with HIV. CONCLUSION: Although additional studies are needed to elucidate this complex association, our results suggest the importance of early detection of both MDD and suicidality in patients living with HIV. PMID- 26279990 TI - Diagnostic assays developed for the control of foot-and-mouth disease in India. AB - Foot-and-mouth disease (FMD) is a highly contagious and economically devastating disease of livestock, primarily affecting cattle, buffalo and pigs. FMD virus serotypes O, A and Asia1 are prevalent in India and systematic efforts are on to control and eventually eradicate the disease from the country. FMD epidemiology is complex due to factors like co-circulation, extinction, emergence and re emergence of genotypes/lineages within the three serotypes, animal movement, diverse farm practices and large number of susceptible livestock in the country. Systematic vaccination, prompt diagnosis, strict biosecurity measures, and regular monitoring of vaccinal immunity and surveillance of virus circulation are indispensible features for the effective implementation of the control measures. Availability of suitable companion diagnostic tests is very important in this endeavour. In this review, the diagnostic assays developed and validated in India and their contribution in FMD control programme is presented. PMID- 26279992 TI - High-Resolution Melting Is a Sensitive, Cost-Effective, Time-Saving Technique for BRAF V600E Detection in Thyroid FNAB Washing Liquid: A Prospective Cohort Study. AB - OBJECTIVE: The diagnostic accuracy of thyroid fine needle aspiration biopsy (FNAB) can be improved by the combination of cytological and molecular analysis. In this study, washing liquids of FNAB (wFNAB) were tested for the BRAF V600E mutation, using the sensitive and cost-effective technique called high-resolution melting (HRM). The aim was to demonstrate the feasibility of BRAF analysis in wFNAB and its diagnostic utility, combined with cytology. DESIGN: Prospective cohort study. METHODS: 481 patients, corresponding to 648 FNAB samples, were subjected to both cytological (on cells smeared onto a glass slide) and molecular analysis (on fluids obtained washing the FNAB needle with 1 ml of saline) of the same aspiration. BRAF V600E analysis was performed by HRM after methodological validation for application to wFNAB (technique sensitivity: 5.4%). RESULTS: The cytological results of the FNAB were: 136 (21%) nondiagnostic (THY1); 415 (64%) benign (THY2); 80 (12.4%) indeterminate (THY3); 9 (1.4%) suspicious for malignancy (THY4); 8 (1.2%) diagnostic of malignancy (THY5). The BRAF V600E mutation was found in 5 THY2, 2 THY3, 6 THY4 and 6 THY5 samples. Papillary carcinoma diagnosis was histologically confirmed in all BRAF+ thyroidectomized patients. BRAF combined with cytology improved the diagnostic value compared to cytology alone in a subgroup of 74 operated patients. CONCLUSIONS: HRM was demonstrated to be a feasible method for BRAF analysis in wFNAB. Thanks to its sensitivity and cost-effectiveness, it might be routinely used on a large scale in clinical practice. In perspective, standby wFNAB samples could be analyzed a posteriori in case of indeterminate cytology and/or suspicious findings on ultrasound. PMID- 26279993 TI - Radioiodine Treatment and Thyroid Hormone Suppression Therapy for Differentiated Thyroid Carcinoma: Adverse Effects Support the Trend toward Less Aggressive Treatment for Low-Risk Patients. AB - Over the past decades, the incidence of differentiated thyroid carcinoma (DTC) has steadily increased, with especially a growing number of low-risk patients. Whereas DTC used to be treated rather aggressively, it is now acknowledged that aggressive treatment does not affect outcome for low-risk patients and that it can induce adverse effects. In this review an overview of the most clinically relevant adverse effects of radioiodine treatment and thyroid hormone suppression therapy (THST) is presented, and the trend toward less aggressive treatment for low-risk patients is outlined. Salivary gland dysfunction occurs in roughly 30% of patients, and is probably due to the concentration of radioiodine in the salivary glands by the sodium/iodide symporter. Beta radiation from radioiodine can result in sialoadenitis and eventually fibrosis and loss of salivary function. Furthermore, patients can experience bone marrow dysfunction following radioiodine treatment. Although this is in general subclinical and transient, patients that receive very high cumulative radioiodine doses may be at risk for more severe bone marrow dysfunction. THST can induce adverse cardiovascular effects in patients with DTC, such as diastolic and systolic dysfunction, and also adverse vascular and prothrombotic effects have been described. Finally, the effects of THST on bone formation and resorption are outlined; especially postmenopausal women with DTC on THST seem to be at risk of bone loss. In the past years, advances have been made in preventing low-risk patients from being overtreated. Improved biomarkers are still needed to further optimize risk stratification and personalize medicine. PMID- 26279994 TI - A Prospective Investigation of Graves' Disease and Selenium: Thyroid Hormones, Auto-Antibodies and Self-Rated Symptoms. AB - BACKGROUND: In Graves' thyrotoxicosis tachycardia, weight loss and mental symptoms are common. Recovery takes time and varies between patients. Treatment with methimazole reduces thyroid hormone levels. According to previous research, this reduction has been faster if selenium (Se) is added. OBJECTIVE: The objective was to investigate whether supplementing the pharmacologic treatment with Se could change the immune mechanisms, hormone levels and/or depression and anxiety. METHODS: We prospectively investigated 38 patients with initially untreated thyrotoxicosis by measuring the thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroid receptor antibodies and thyroid peroxidase auto-antibodies before medication and at 6, 18 and 36 weeks after commencing treatment with methimazole and levo-thyroxine, with a randomized blinded oral administration of 200 ug Se/day or placebo. The selenoprotein P concentration was determined in plasma at inclusion and after 36 weeks. The patients were also assessed with questionnaires about depression, anxiety and self-rated symptoms before medication was started and after 36 weeks. RESULTS: FT4 decreased more in the Se group at 18 weeks (14 vs. 17 pmol/l compared to the placebo group, p = 0.01) and also at 36 weeks (15 vs. 18 pmol/l, p = 0.01). The TSH increased more in the Se group at 18 weeks (0.05 vs. 0.02 mIU/l, p = 0.04). The depression and anxiety scores were similar in both groups. In the Se group, the depression rates correlated negatively with FT3 and positively with TSH. This was not seen in the placebo group. CONCLUSIONS: Se supplementation can enhance biochemical restoration of hyperthyroidism, but whether this could shorten clinical symptoms of thyrotoxicosis and reduce mental symptoms must be investigated further. PMID- 26279995 TI - Assessment of the Effect of Two Distinct Restricted Iodine Diet Durations on Urinary Iodine Levels (Collected over 24 h or as a Single-Spot Urinary Sample) and Na(+)/I(-) Symporter Expression. AB - INTRODUCTION: A restricted iodine diet (RID) may be recommended for depletion of the whole-body iodine pool in patients with differentiated thyroid cancer referred for radioiodine treatment or a whole-body scan. Evaluation of the iodine pool is possible through urinary iodide (UI) measurements, which can be collected in 24-hour (24U) or spot urinary (sU) samples. However, the minimum period required for an RID to lower the iodine pool, the measurement of iodine in sU samples as a iodine pool marker, and the influence of the iodine pool on Na(+)/I( ) symporter (NIS) expression are debatable in the literature. OBJECTIVES: To compare the effects of 15- and 30-day RID on UI measurements in 24U and sU samples and the impact of RID on NIS expression. METHODS: Thyroidectomized patients went on a 15- or 30-day RID and collected 24U and sU samples before and after the RID. Twenty healthy individuals were evaluated for mRNA NIS expression before and after the RID. RESULTS: Of 306 patients, only 125 properly complied with both the RID and 24U collection. We observed a correlation between sU and 24U UI before the RID (n = 306, rho = 0.47, p < 0.001), after a 15-day RID (n = 79, rho = 0.49, p < 0.001), and after a 30-day RID (n = 46, rho = 0.73, p < 0.001). There was a significant decrease in UI after the RID. The median UI measurement was 275 MUg/l at baseline and 99 and 80 MUg/l after a 15- and 30-day RID, respectively. There was a significant increase in NIS expression after a 15 day RID. CONCLUSIONS: A 15-day RID is sufficient to deplete the iodine pool. sU can replace 24U UI as a marker for assessing the iodine pool. NIS expression was increased after a 15-day RID. PMID- 26279996 TI - Evaluation of Thyroid Bed Nodules on Ultrasonography after Total Thyroidectomy: Risk for Loco-Regional Recurrence of Thyroid Cancer. AB - OBJECTIVES: We conducted a retrospective chart review of patients with differentiated thyroid cancer who underwent total thyroidectomy to examine the correlation of the persistence of thyroid bed nodules seen on ultrasonography with subsequent loco-regional recurrence. METHODS: A total of 60 patients with differentiated thyroid cancer were identified who underwent total thyroidectomy, received (131)I therapy and had thyroid bed nodules on postoperative surveillance ultrasonography. The ultrasonographic features of the thyroid bed nodules and their progression over time along with serum thyroglobulin (Tg) levels were monitored. Those patients who demonstrated no evidence of recurrence were compared to patients who had recurrence. RESULTS: Of the 60 patients, 25% had documented cancer recurrence. Sixty percent of the patients in the recurrence group had an increase in the size of bed nodules as compared to only 7% of the patients in the group without recurrence. An increase in serum Tg of more than 2 fold was seen in 80% of the patients with recurrence and in only 13% (6/45) of the patients without cancer recurrence. The odds of identifying recurrent thyroid cancer in patients with more than a 2-fold increase in serum Tg were 80.5 greater than in patients with a less than 2-fold increase in serum Tg. The odds of identifying recurrent thyroid cancer in patients with the presence of any suspicious thyroid bed nodule were 31.5 times greater than in patients without suspicious thyroid bed nodules. CONCLUSIONS: Thyroid bed nodules on surveillance ultrasound warrant fine-needle aspiration cytology if they increase in size and number, are persistent and associated with suspicious sonographic features. PMID- 26279997 TI - Incidence and Significance of Incidental Focal Thyroid Uptake on (18)F-FDG PET Study in a Large Patient Cohort: Retrospective Single-Centre Experience in the United Kingdom. AB - OBJECTIVE: To assess the prevalence and pathological nature of incidental focal thyroid uptake on (18)F-FDG (2-[(18)F]-fluoro-2-deoxy-D-glucose) PET (positron emission tomography) and examine the role of the maximum standardised uptake value (SUVmax) to differentiate benign from malignant thyroid pathology. MATERIAL AND METHODS: (18)F-FDG PET reports were retrospectively reviewed. Incidental focal tracer uptake in the thyroid was noted in 147 patients (0.5%). Patients with known primary thyroid malignancy were excluded. The final diagnosis was made following ultrasonography of the neck, fine-needle aspiration cytology (FNAC) or histopathology of the surgically resected specimen where surgery was indicated. A Mann-Whitney U test was used to compare the SUVmax of benign and malignant thyroid pathology. Receiver operating characteristic (ROC) analysis was performed to identify an SUVmax cutoff in differentiating benign from malignant pathology. RESULTS: A final diagnosis was achieved in 47/147 (32%) of the patients. The diagnoses included benign lesions in 36 patients and malignancy in 9 patients. In 2 patients, FNAC demonstrated indeterminate follicular lesions; however, surgical excision was not performed. There was a highly significant difference in the mean SUVmax of malignant focal thyroid uptake (15.7 +/- 5.9) compared to that of benign lesions (7.1 +/- 6.8) with a p value of 0.000123. An SUVmax of 9.1 achieved a sensitivity of 81.6%, specificity of 100% and area under the curve of 0.915 in the ROC analysis differentiating benign from malignant disease. CONCLUSION: The malignancy potential of incidental focal thyroid uptake remains high and warrants prompt and appropriate follow-up by the clinician. The SUVmax may aid in further characterisation of the lesion and its management. PMID- 26279998 TI - Prevalence of Cancer in Patients with Thyroid Nodules in the Island of Cyprus: Predictive Value of Ultrasound Features and Thyroid Autoimmune Status. AB - BACKGROUND: The purpose of this study was to determine the prevalence of thyroid carcinoma in patients who underwent ultrasound-guided fine needle aspiration biopsy (USgFNA) of thyroid nodules in the island of Cyprus. Ultrasound features as well as the presence of autoimmune thyroid disease were evaluated as risk factors for malignancy. METHODS: 322 consecutively examined patients (272 females/50 males, age 13-81) underwent USgFNA of thyroid nodules in a referral endocrine clinic between July 2007 and July 2009. The ultrasonographic characteristics examined were: echogenicity, margin irregularity, composition, calcifications, presence of increased vasculature and nodule size. The presence or absence of autoimmune thyroid disease was recorded. RESULTS: From the 548 nodules examined, 74 (13.6%) were classified as THY3, 4 or 5. 75 patients (123 nodules) underwent surgical resection. 46 patients (64 nodules) proved to have thyroid carcinoma by histology. There was a significant correlation of suspicious/malignant cytology with solid composition, hypoechogenicity, irregular margins and the presence of calcifications. A significant association was also noted between the presence of positive antithyroglobulin antibodies (p < 0.05) and Graves' disease (p = 0.01) with suspicious/malignant cytology. CONCLUSION: The overall prevalence of thyroid cancer was 14.3%. Ultrasound characteristics were highly predictive of thyroid malignancy. Thyroid autoimmunity should be considered as a risk factor. PMID- 26279999 TI - Nonthyroidal Illness Syndrome in Cardiac Illness Involves Elevated Concentrations of 3,5-Diiodothyronine and Correlates with Atrial Remodeling. AB - BACKGROUND: Although hyperthyroidism predisposes to atrial fibrillation, previous trials have suggested decreased triiodothyronine (T3) concentrations to be associated with postoperative atrial fibrillation (POAF). Therapy with thyroid hormones (TH), however, did not reduce the risk of POAF. This study reevaluates the relation between thyroid hormone status, atrial electromechanical function and POAF. METHODS: Thirty-nine patients with sinus rhythm and no history of atrial fibrillation or thyroid disease undergoing cardiac surgery were prospectively enrolled. Serum concentrations of thyrotropin, free (F) and total (T) thyroxine (T4) and T3, reverse (r)T3, 3-iodothyronamine (3-T1AM) and 3,5 diiodothyronine (3,5-T2) were measured preoperatively, complemented by evaluation of echocardiographic and electrophysiological parameters of cardiac function. Holter-ECG and telemetry were used to screen for POAF for 10 days following cardiac surgery. RESULTS: Seven of 17 patients who developed POAF demonstrated nonthyroidal illness syndrome (NTIS; defined as low T3 and/or low T4 syndrome), compared to 2 of 22 (p < 0.05) patients who maintained sinus rhythm. In patients with POAF, serum FT3 concentrations were significantly decreased, but still within their reference ranges. 3,5-T2 concentrations directly correlated with rT3 concentrations and inversely correlated with FT3 concentrations. Furthermore, 3,5 T2 concentrations were significantly elevated in patients with NTIS and in subjects who eventually developed POAF. In multivariable logistic regression FT3, 3,5-T2, total atrial conduction time, left atrial volume index and Fas ligand were independent predictors of POAF. CONCLUSION: This study confirms reduced FT3 concentrations in patients with POAF and is the first to report on elevated 3,5 T2 concentrations in cardiac NTIS. The pathogenesis of NTIS therefore seems to involve more differentiated allostatic mechanisms. PMID- 26280000 TI - Do Not Forget Nephrotic Syndrome as a Cause of Increased Requirement of Levothyroxine Replacement Therapy. AB - Nephrotic syndrome increases L-thyroxine requirements because of urinary loss of free and protein-bound thyroid hormones. We report 2 hypothyroid patients referred to us because of high serum TSH, even though the L-thyroxine daily dose was maintained at appropriate levels or was increased. The cause of nephrotic syndrome was multiple myeloma in one patient and diabetic glomerulosclerosis in the other patient. As part of the periodic controls for diabetes, urinalysis was requested only in the second patient so that proteinuria could be detected. However, as in the first patient, facial puffiness and body weight increase were initially attributed to hypothyroidism, which was poorly compensated by L thyroxine therapy. In the first patient, the pitting nature of the pedal edema was missed at the initial examination. An endocrinologist consulted over the phone by the practitioner hypothesized some causes of intestinal malabsorption of L-thyroxine. This diagnosis would have been accepted had the patient continued taking a known sequestrant of L-thyroxine, i.e. calcium carbonate. The diagnostic workup of patients with increasing requirements of L-thyroxine replacement therapy should not be concentrated on the digestive system alone. Careful history taking and physical examination need to be thorough. Endocrinologists should not forget nephrotic syndrome that, in turn, can be secondary to serious diseases. PMID- 26280001 TI - Biomarkers and Personalized Sorafenib Therapy. PMID- 26280003 TI - Alteration of Epigenetic Profile in Human Hepatocellular Carcinoma and Its Clinical Implications. AB - Hepatocellular carcinoma (HCC) is a common cancer worldwide and develops against a background of chronic liver damage. A variety of HCC-related genes are known to be altered by genetic and epigenetic mechanisms. Therefore, information regarding alteration of the genetic and epigenetic profiles in HCC is essential for understanding the biology of this type of tumor. Methylation at CpG sites in gene promoters is known to affect the transcription of the corresponding genes. Abnormal regional hypermethylation is observed in the 5' region of several tumor suppressor genes (TSGs) in HCC, and this hypermethylation may promote carcinogenesis through the transcriptional inactivation of downstream TSGs. The DNA damage induced by oxidation is a trigger of abnormal DNA methylation and inactivation of TSGs through recruitment of the polycomb repressive complex to the promoter sequence. Thus, oxidative stress may be responsible for the emergence of HCC from chronic hepatitis and liver cirrhosis through the epigenetic alteration of TSGs. There have been several attempts to apply epigenetic information to the diagnosis and treatment of HCC. The predictive value of selected methylation events on survival in HCC patients has been reported, and the methylation profile of background liver could be associated with recurrence-free survival of HCC patients who have undergone hepatectomy. Another study detected methylated DNA from HCC cells in serum, and the circulating tumor DNA was regarded as a potential tumor marker. In addition, several trials of HCC therapy have targeted the epigenetic machinery and were based upon comprehensive analyses of DNA methylation of this type of tumor. Here, we present an overview of research regarding DNA methylation status in human HCC and describe the clinical application of epigenetic information to HCC. PMID- 26280002 TI - Multimodality Management for Barcelona Clinic Liver Cancer Stage C Hepatocellular Carcinoma. AB - This review summarizes the contents of a workshop on multimodality management for Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) held on July 6, 2013, under the auspices of the 4th Asia-Pacific Primary Liver Cancer Expert Meeting Scientific Advisory Committee. BCLC stage C HCC represents a varied disease spectrum and, therefore, further stratification of BCLC stage C should be explored. Although sorafenib is currently the standard treatment for BCLC stage C HCC, the survival benefits are modest and new treatment strategies are still needed. Based on the opinions of Asian experts, there are numerous alternative options aside from sorafenib for the treatment of BCLC stage C HCC, including surgical resection, hepatic arterial infusion chemotherapy, transarterial chemoembolization, and external radiotherapy. Moreover, there are several studies on the multimodality management of BCLC stage C HCC, mainly in the form of retrospective studies and a few phase I and II trials. Multimodality management with combinations of various locoregional therapies or locoregional therapies with systemic targeted therapy using sorafenib needs to be actively investigated. The Asia-Pacific clinical practice guidelines on multimodality management for BCLC stage C HCC need recommendations based on the level of evidence, the strength of the data, and the strength of recommendations of previously reported systems. PMID- 26280005 TI - Using Modified RECIST and Alpha-Fetoprotein Levels to Assess Treatment Benefit in Hepatocellular Carcinoma. AB - BACKGROUND AND AIMS: Assessing treatment responses in hepatocellular carcinoma (HCC) is challenging, and alternative radiologic methods of measuring treatment response are required. Modified Response Evaluation Criteria in Solid Tumors (mRECIST) for HCC and alpha-fetoprotein (AFP) levels were assessed in a post hoc analysis of a phase II study of brivanib, a selective dual inhibitor of fibroblast growth factor and vascular endothelial growth factor signaling. METHODS: HCC patients were treated with first-line (cohort A; n = 55) or second line (cohort B; n = 46) brivanib alaninate 800 mg once daily. Outcomes were compared between World Health Organization (WHO) criteria and (retrospectively by) mRECIST by independent review. The relationship between on-study AFP changes and outcome was analyzed in patients with elevated AFP at baseline. RESULTS: Response rates were higher with mRECIST versus WHO criteria in cohorts A (25.5% vs. 7.3%) and B (10.9% vs. 4.3%). Progressive disease (PD) as assessed by mRECIST was associated with a very short median overall survival (OS; cohort A, 2.8 months; cohort B, 5.3 months); PD as assessed by WHO criteria reflected a mixed population of patients with better outcomes. mRECIST responders tended to have a>50% AFP decrease during therapy. In cohorts A and B pooled, an early AFP response (>20%or >50% decline from baseline within the first 4 weeks) was not associated with longer median OS. CONCLUSIONS: Tumor response as assessed by mRECIST differed from that by WHO criteria, with mRECIST possibly identifying true nonresponders with a poor prognosis. Many patients had AFP decreases correlating with tumor shrinkage, yet an association with long-term benefit was unclear. mRECIST and on-treatment AFP levels are being explored further with brivanib in HCC. PMID- 26280004 TI - Management of Hepatocellular Carcinoma in Cirrhotic Patients with Portal Hypertension: Relevance of Hagen-Poiseuille's Law. AB - BACKGROUND: Hepatic decompensation in cirrhosis heralds an accelerated course with poor survival. An increase in hepatic venous pressure gradient (HVPG), rather than surrogate tests of liver function, appears to be the sole predictor of decompensation after surgical resection. We propose that hepatic sinusoidal walls become less elastic as cirrhosis progresses. Decompensation signals the development of increased vessel wall rigidity. The pressure-flow characteristics then become subject to Hagen-Poiseuille's law, which applies only to rigid, cylindrical vessels. Thereafter, HVPG rises exponentially (by a factor inversely proportional to the fourth power of the net radius of functional sinusoidal vessels, 1/r(4), at any given hepatic blood flow rate. This review attempts to correlate liver stiffness, risk of decompensation and outcomes from hepatocellular carcinoma (HCC) in patients with cirrhosis. SUMMARY: We compare the complexity of autoregulation in the normal elastic liver, which has a unique dual blood supply, with that in the rigid cirrhotic liver. We also review, in the context of background liver cirrhosis, the management of HCC which is in essence, a solid mass of unorganized cells that exacerbates liver stiffness. We discuss the differential effects of various therapeutic modalities such as liver transplantation, loco-regional therapy and drugs on HCC outcomes, based on their effects on HVPG. KEY MESSAGES: Increased hepatic artery supply, or the hepatic artery buffer response, may be the only available method for autoregulation or maintenance of hepatic blood flow in the cirrhotic liver. In HCC, loco-regional therapies, including partial resection of the cirrhotic liver, can exacerbate portal hypertension by increasing blood flow within the remnant organ. We conclude that studies of HVPG reduction as part of HCC management may be beneficial and are warranted. PMID- 26280006 TI - Overexpression of Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 5 (LGR5) Represents a Typical Wnt/beta-Catenin Pathway-Activated Hepatocellular Carcinoma. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common and most frequently lethal cancers worldwide. Although many advances have been made in the analysis of multistage hepatocarcinogenesis, we still lack information to guide adequate clinical management options for HCC. A large number of genetic alterations occur during hepatocarcinogenesis, and many genetic studies have indicated that one of the most frequently mutated oncogenes found in HCC is beta catenin. SUMMARY: Molecular subclassification of HCC based on gene expression signatures has identified a typical hepatocyte-like subclass of HCC harboring beta-catenin mutations; this subclass is characterized by better histological differentiation and a less aggressive nature. We previously identified overexpression of the leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), also known as GPR49, in HCC with beta-catenin mutations. LGR5 has been indicated as one of the downstream target genes of the Wnt signaling pathway; however, the functional role of LGR5 in cancer is largely unknown. We demonstrated that HCC cells transfected with LGR5 exhibited higher colony forming activity and were more resistant to a cytotoxic drug than the control HCC cells were. Overexpression of LGR5 also retarded cell migration. LGR5-transfected HCC cells formed nodule-type tumors in the livers of immunodeficient mice, whereas control cells formed more invasive tumors. Results of our recent research suggest that aberrant expression of LGR5 could regulate the epithelial cell phenotype and promotes HCC cell survival. HCC cells overexpressing LGR5 seem to represent a typical phenotype of a less aggressive HCC. KEY MESSAGES: Recent efforts on the molecular classification of HCC have led us to new strategies for dealing with HCC. These specific signatures may predict the risk of recurrence or the patient survival rate, which affect the outlook and may suggest treatment strategies for HCC patients. PMID- 26280008 TI - The association between periodontal disease and metabolic syndrome among outpatients with diabetes in Jordan. AB - BACKGROUND: To date, conflicting results have been reported about the association between metabolic syndrome (MetS) and periodonttitis. METHODS: Two hundred and eighty patients with type 2 diabetes were recruited from outpatients visiting diabetes clinics in Islamic Hospital, Amman-Jordan. The oral hygiene and the periodontal status of all teeth, excluding third molars, were assessed using the plaque index of Silness and Loe, the gingival index of Loe and Silness, probing pocket depth (PPD), and clinical attachment level (CAL). Data were analyzed using the general linear model multivariate procedure with average PPD, average CAL, percent of teeth with CAL >=3 mm, and percent of teeth with PPD >=3 mm as outcome variables and diabetes, MetS and its individual components as predictors. RESULTS: Overall, 83.2 % of patients with diabetes had MetS. In the multivariate analysis, patients with MetS had a significantly more severe periodontitis, as measured by average PPD and average CAL (P < 0.005). The extent of periodontitis, as measured by the percent of teeth with CAL >=3 mm and the percent of teeth with PPD >=3 mm, was also significantly greater among patients with MetS (P < 0.005). As the number of metabolic components additional to diabetes increased, the odds of having periodontitis increased, and the odds were greatest when all the components additional to diabetes were present (OR = 10.77, 95 % CI: 2.23 51.95). CONCLUSION: Patients with MetS displayed more severe and extensive periodontitis. Having other MetS components additional to diabetes increased the odds of having periodontitis. PMID- 26280007 TI - JSH Consensus-Based Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma: 2014 Update by the Liver Cancer Study Group of Japan. AB - The Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma proposed by the Japan Society of Hepatology was updated in June 2014 at a consensus meeting of the Liver Cancer Study Group of Japan. Three important items have been updated: the surveillance and diagnostic algorithm, the treatment algorithm, and the definition of transarterial chemoembolization (TACE) failure/refractoriness. The most important update to the diagnostic algorithm is the inclusion of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid enhanced magnetic resonance imaging as a first line surveillance/diagnostic tool. Another significant update concerns removal of the term "lipiodol" from the definition of TACE failure/refractoriness. PMID- 26280009 TI - Assessment of functional improvement with temporalis myofascial flap after condylectomy in elderly patients with anterior disc displacement without reduction and an erosive condylar surface. AB - BACKGROUND: The purpose of this study was to investigate the functional effects of temporalis myofascial flap after condylectomy, with or without disc removal, in elderly patients with anterior disc displacement (ADD) without reduction and an erosive condylar surface of the temporomandibular joint (TMJ). METHODS: A total of 15 joints from 11 elderly patients (71-78 years old) were included. The patients had pain, mandibular dysfunction symptoms, and unilateral or bilateral ADD as well as an erosive condylar surface of the TMJ. All patients underwent temporalis myofascial flap reconstruction after condylectomy, with or without disc removal. If the maximal mouth opening (MMO) remained <35 mm after condylectomy, coronoidotomy was also performed. Self-assessed pain and mandibular function, including MMO and protrusive and lateral movements, were evaluated. RESULTS: No patient experienced serious complications. Most measurements improved significantly after surgery compared to preoperatively. Most patients achieved nearly-normal mouth opening at 4 weeks after surgery. Although most patients felt discomfort during active postoperative physiotherapy, no patient reported serious pain during the follow-up period. CONCLUSION: Although nonsurgical therapy is often the first treatment choice for ADD without reduction of the TMJ, surgical intervention involving condylectomy and temporalis myofascial flap reconstruction may be a reasonable first option for elderly patients with an erosive condylar surface of the TMJ. PMID- 26280010 TI - A quantitative, surface plasmon resonance-based approach to evaluating DNA binding by the c-Myc oncoprotein and its disruption by small molecule inhibitors. AB - The use of small molecules to interfere with protein-protein interactions has tremendous therapeutic appeal and is an area of intense interest. Numerous techniques exist to assess these interactions and their disruption. Many, however, require large amounts of protein, do not allow interactions to be followed in real time, are technically demanding or require large capital expenditures and high levels of expertise. Surface plasmon resonance (SPR) represents a convenient alternative to these techniques with virtually none of their disadvantages. We have devised an SPR-based method that allows the heterodimeric association between the c-Myc (Myc) oncoprotein and its obligate partner Max to be quantified in a manner that agrees well with values obtained by other methods. We have adapted it to examine the ability of previously validated small molecules to interfere with Myc-Max heterodimerization and DNA binding. These inhibitors comprised two distinct classes of molecules that inhibit DNA binding by preventing Myc-Max interaction or distorting pre-formed heterodimers and rendering them incapable of DNA binding. Our studies also point out several potential artifacts and pitfalls to be considered when attempting to employ similar SPR-based methods. This technique should be readily adaptable to the study of other protein-protein interactions and their disruption by small molecules. PMID- 26280011 TI - Fatal Granulomatous Amoebic Encephalitis Caused by Acanthamoeba in a Patient With Kidney Transplant: A Case Report. AB - Granulomatous amoebic encephalitis (GAE) due to Acanthamoeba is almost a uniformly fatal infection in immune-compromised hosts despite multidrug combination therapy. We report a case of GAE in a female who received a deceased donor kidney graft. She was treated with a combination of miltefosine, pentamidine, sulfadiazine, fluconazole, flucytosine, and azithromycin. PMID- 26280012 TI - The first anniversary issue. PMID- 26280013 TI - Unique invariant CD8(+) T cell population persists in MS. PMID- 26280014 TI - CSF cytokine profile distinguishes multifocal motor neuropathy from progressive muscular atrophy. AB - OBJECTIVE: We aimed to compare the cytokine and chemokine profiles of patients with multifocal motor neuropathy (MMN) with those of patients with progressive muscular atrophy (PMA) and amyotrophic lateral sclerosis (ALS) to investigate immunologic differences in the CNS. METHODS: CSF from 12 patients with MMN, 8 with PMA, 26 with sporadic ALS, and 10 with other noninflammatory neurologic disorders was analyzed for 27 cytokines and chemokines using the multiplex bead array assay. Cytokine titers of the 4 groups were compared, and correlations between the titers of relevant cytokines and clinical parameters were evaluated. RESULTS: There were no obvious intrathecal changes except for interleukin (IL)-1 receptor antagonist in patients with MMN. In contrast, IL-4, IL-7, IL-17, eotaxin/CCL11, fibroblast growth factor-2 (FGF-2), granulocyte colony-stimulating factor (G-CSF), and platelet-derived growth factor BB titers were significantly elevated in patients with PMA and ALS; of these, FGF-2 and G-CSF titers were elevated compared with those in patients with MMN. IL-4 and IL-10 titers were high in patients with ALS, particularly patients with possible ALS presenting with a slowly progressive course or mild symptoms. CONCLUSIONS: The CSF cytokine profile of patients with MMN is distinct from that of patients with PMA and ALS. The similarity of the cytokine profiles between patients with PMA and ALS suggests that PMA shares common immunologic features with ALS in the CNS, even without clinical evidence of upper motor neuron involvement. PMID- 26280015 TI - Macrophage migration inhibitory factor promotes resistance to glucocorticoid treatment in EAE. AB - OBJECTIVE: Glucocorticoids (GCs) are used as standard treatment for acute attacks of multiple sclerosis (MS). However, GCs eventually lose efficacy and do not prevent disease progression. Macrophage migration inhibitory factor (MIF) is the only known proinflammatory cytokine induced by GCs that inhibits their anti inflammatory effects. Therefore, we investigated whether MIF plays a role in resistance to GC treatment in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. METHODS: EAE was induced in wild-type (Wt) and MIF knockout (MIF(-/-)) mice followed by treatment with dexamethasone (Dex) before or upon disease onset. Splenocytes and brain mononuclear cells were harvested for cytokine ELISPOT assay and flow cytometry analysis. RESULTS: Treatment of EAE with Dex was substantially more efficacious in MIF(-/-) mice than Wt mice. Dex treatment decreased MOG35-55-induced cytokine production by Wt or MIF(-/-) CD4(+) T cells only at the onset of EAE but inhibited upregulation of T-bet during acute and chronic phases of disease, particularly in MIF(-/-) mice. Furthermore, passive EAE induced by adoptive transfer of T cells showed that Dex was highly effective in ameliorating disease induced by MIF(-/-) CD4(+) T cells but not by Wt CD4(+) T cells. The expression of T-bet and VLA-4 was decreased in CD4(+) T cells in MIF(-/-) mice compared with Wt mice. CONCLUSIONS: Our data establish MIF as a key molecule in resistance of pathogenic CD4(+) T cells to GC treatment in EAE and as a potential target to enhance the effectiveness of steroid treatment in neuroinflammatory disorders. PMID- 26280016 TI - Migration, sexual behaviour, and HIV risk: a general population cohort in rural South Africa. AB - BACKGROUND: Increased sexual risk behaviour and HIV prevalence have been reported in migrants compared with nonmigrants in sub-Saharan Africa. We investigated the association of residential and migration patterns with sexual HIV risk behaviours and HIV prevalence in an open, general population cohort in rural KwaZulu-Natal, South Africa. METHODS: In a mainly rural demographic surveillance area in northern KwaZulu-Natal, South Africa, we collected longitudinal demographic, migration, sexual behaviour, and HIV status data through household surveillance twice per year and individual surveillance once per year. All resident household members and a sample of non-resident household members (stratified by sex and migration patterns) were eligible for participation. Participants reported sexual risk behaviours, including data for multiple, concurrent, and casual sexual partners and condom use, and gave a dried blood spot sample via fingerprick for HIV testing. We investigated population-level differences in sexual HIV risk behaviours and HIV prevalence with respect to migration indicators using logistic regression models. FINDINGS: Between Jan 1, 2005, and Dec 31, 2011, the total eligible population at each surveillance round ranged between 21 129 and 22 726 women (aged 17-49 years) and between 20 399 and 22 100 men (aged 17-54 years). The number of eligible residents in any round ranged from 24 395 to 26 664 and the number of eligible non-residents ranged from 17 002 to 18 891 between rounds. The stratified sample of non-residents included between 2350 and 3366 individuals each year. Sexual risk behaviours were significantly more common in non-residents than in residents for both men and women. Estimated differences in sexual risk behaviours, but not HIV prevalence, varied between the migration indicators: recent migration, mobility, and migration type. HIV prevalence was significantly increased in current residents with a recent history of migration compared with other residents in the study area in men(adjusted odds ratio 1.19, 95% CI 1.07 1.33) and in women (1.18, 1.10-1.26). INTERPRETATION: Local information about migrants and highly mobile individuals could help to target intervention strategies that are based on the identification of transmission hotspots.Funding Wellcome Trust. PMID- 26280017 TI - New agents for the treatment of lymphoid leukemia and lymphoma: focus on recent FDA approvals. AB - Leukemia and lymphoma are systemic malignancies that represent half of all childhood cancers, though 90% occur in adults. Various treatment options are available, but therapy is mainly systemic chemotherapy plus appropriate monoclonal antibodies. In certain situations radiotherapy and bone marrow transplantation play a role. Some types/subtypes of these diseases are potentially curable, yet many leukemias and lymphomas do not properly respond to current therapies. Although the FDA (US Food and Drugs Administration) approvals of new drugs have shown a small increasing trend between 2007-2012, overall, the trend of new approvals remains relatively steady between 2006-2013, with a peak of 39 new drugs approved in 2012 and a drop in the new FDA drug approvals in 2013, to 27. Drugs approved for cancer treatment have shown a similar trend. Between 2006-2013, at least one drug was approved every year for the treatment of particular types of lymphoma or leukemia, except in 2010, with a peak of 5 new approvals in 2012. Between January 2013-March 2014, several important new approvals were made: ibrutinib for the treatment of CLL and mantle cell lymphoma (MCL), obinutuzumab for the treatment of CLL (in combination with chlorambucil), and lenalidomide for the treatment of mantle cell lymphoma. The results, importance, adverse effects and mechanisms of action of these agents are discussed in this review. These results held promise and their discovery and approval for the treatment of CLL and MCL is a major step forward. However, the emergence of resistance and the lack of cures need to be addressed by rational development of combination therapy, as well as development of novel drugs with enhanced potency or different mechanism of action, to achieve better overall and complete response rates with decreased toxicity. PMID- 26280018 TI - PLK1 is a binding partner and a negative regulator of FOXO3 tumor suppressor. AB - FOXO family members (FOXOs: FOXO1, FOXO3, FOXO4 and FOXO6) are important transcription factors and tumor suppressors controlling cell homeostasis and cell fate. They are characterized by an extraordinary functional diversity, being involved in regulation of cell cycle, proliferation, apoptosis, DNA damage response, oxidative detoxification, cell differentiation and stem cell maintenance, cell metabolism, angiogenesis, cardiac and other organ's development, aging, and other critical cellular processes. FOXOs are tightly regulated by reversible phosphorylation, ubiquitination, acetylation and methylation. Interestingly, the known kinases phosphorylate only a small percentage of the known or predicted FOXOs phosphorylation sites, suggesting that additional kinases that phosphorylate and control FOXOs activity exist. In order to identify novel regulators of FOXO3, we have employed a proteomics screening strategy. Using HeLa cancer cell line and a Tandem Affinity Purification followed by Mass Spectrometry analysis, we identified several proteins as binding partners of FOXO3. Noteworthy, Polo Like Kinase 1 (PLK1) proto-oncogene was one of the identified FOXO3 binding partners. PLK1 plays a critical role during cell cycle (G2-M transition and all phases of mitosis) and in maintenance of genomic stability. Our experimental results presented in this manuscript demonstrate that FOXO3 and PLK1 exist in a molecular complex through most of the phases of the cell cycle, with a higher occurrence in the G2-M cell cycle phases. PLK1 induces translocation of FOXO3 from the nucleus to the cytoplasm and suppresses FOXO3 activity, measured by the decrease in the pro-apoptotic Bim protein levels and in the cell cycle inhibitor protein p27. Furthermore, PLK1 can directly phosphorylate FOXO3 in an in vitro kinase assay. These results present the discovery of PLK1 proto-oncogene as a binding partner and a negative regulator of FOXO3 tumor suppressor. PMID- 26280019 TI - Biomimetic Material-Assisted Delivery of Human Embryonic Stem Cell Derivatives for Enhanced In Vivo Survival and Engraftment. AB - The ability of human embryonic stem cells (hESCs) and their derivatives to differentiate and contribute to tissue repair has enormous potential to treat various debilitating diseases. However, improving the in vivo viability and function of the transplanted cells, a key determinant of translating cell-based therapies to the clinic, remains a daunting task. Here, we develop a hybrid biomaterial consisting of hyaluronic acid (HA) grafted with 6-aminocaproic acid moieties (HA-6ACA) to improve cell delivery and their subsequent in vivo function using skeletal muscle as a model system. Our findings show that the biomimetic material-assisted delivery of hESC-derived myogenic progenitor cells into cardiotoxin-injured skeletal muscles of NOD/SCID mice significantly promotes survival and engraftment of transplanted cells in a dose-dependent manner. The donor cells were found to contribute to the regeneration of damaged muscle fibers and to the satellite cell (muscle specific stem cells) compartment. Such biomimetic cell delivery vehicles that are cost-effective and easy-to-synthesize could play a key role in improving the outcomes of other stem cell-based therapies. PMID- 26280021 TI - 3D Face Hallucination from a Single Depth Frame. AB - We present an algorithm that takes a single frame of a person's face from a depth camera, e.g., Kinect, and produces a high-resolution 3D mesh of the input face. We leverage a dataset of 3D face meshes of 1204 distinct individuals ranging from age 3 to 40, captured in a neutral expression. We divide the input depth frame into semantically significant regions (eyes, nose, mouth, cheeks) and search the database for the best matching shape per region. We further combine the input depth frame with the matched database shapes into a single mesh that results in a highresolution shape of the input person. Our system is fully automatic and uses only depth data for matching, making it invariant to imaging conditions. We evaluate our results using ground truth shapes, as well as compare to state-of the-art shape estimation methods. We demonstrate the robustness of our local matching approach with high-quality reconstruction of faces that fall outside of the dataset span, e.g., faces older than 40 years old, facial expressions, and different ethnicities. PMID- 26280020 TI - High and low molecular weight hyaluronic acid differentially influence macrophage activation. AB - Macrophages exhibit phenotypic diversity permitting wide-ranging roles in maintaining physiologic homeostasis. Hyaluronic acid, a major glycosaminoglycan of the extracellular matrix, has been shown to have differential signaling based on its molecular weight. With this in mind, the main objective of this study was to elucidate the role of hyaluronic acid molecular weight on macrophage activation and reprogramming. Changes in macrophage activation were assessed by activation state selective marker measurement, specifically quantitative real time polymerase chain reaction, and cytokine enzyme-linked immunoassays, after macrophage treatment with differing molecular weights of hyaluronic acid under four conditions: the resting state, concurrent with classical activation, and following inflammation involving either classically or alternatively activated macrophages. Regardless of initial polarization state, low molecular weight hyaluronic acid induced a classically activated-like state, confirmed by up regulation of pro-inflammatory genes, including nos2, tnf, il12b, and cd80, and enhanced secretion of nitric oxide and TNF-alpha. High molecular weight hyaluronic acid promoted an alternatively activated-like state, confirmed by up regulation of pro-resolving gene transcription, including arg1, il10, and mrc1, and enhanced arginase activity. Overall, our observations suggest that macrophages undergo phenotypic changes dependent on molecular weight of hyaluronan that correspond to either (1) pro-inflammatory response for low molecular weight HA or (2) pro-resolving response for high molecular weight HA. These observations bring significant further understanding of the influence of extracellular matrix polymers, hyaluronic acid in particular, on regulating the inflammatory response of macrophages. This knowledge can be used to guide the design of HA-containing biomaterials to better utilize the natural response to HAs. PMID- 26280022 TI - Can Speed of Processing Training Ameliorate Depressive Symptomatology in Adults with HIV? AB - Despite advances in combination Antiretroviral Therapy (cART), adults with HIV continue to experience cognitive impairments. In addition to these cognitive impairments, research suggests as many as 40% and 20% of adults with HIV are diagnosed with depression and anxiety, respectively. The impact of these cognitive and emotional deficits increases caregiver burden, impairs occupational and driving performance, contributes to poor emotional processing, increases cognitive complaints, and reduces quality of life. Fortunately, cognitive remediation therapy improves targeted cognitive abilities along with general cognitive processes. Speed of processing training, a type of cognitive remediation therapy, has been shown to improve cognitive performance on measures of visual attention, speed of processing, and timed-task performances. Furthermore, studies suggest that speed of processing training could also enhance neuromodulatory systems which have direct implications for improving mood functions (depression and anxiety). The benefits of the improvement in these cognitive and emotional systems are a decrease or slowing in cognitive decline along with the potential to protect against clinically significant depressive symptoms. Studies support the need for deeper investigation into the short-term and long-term benefits of speed of processing training as a behavioral adjunct for the pharmacologically-burdened HIV population. PMID- 26280023 TI - The Vanishing Clot. PMID- 26280025 TI - Cerebral Amyloid Angiopathy: A Hidden Risk for IV Thrombolysis? AB - Recombinant tissue plasminogen activator (t-PA) is the only FDA approved therapy for acute ischemic stroke. Cerebral microbleeds (CMBs) or cerebral amyloid angiopathy (CAA) are currently not contraindications, however, data regarding this complex issue are limited. We report 2 cases of fatal intracerebral hemorrhage (sICH) after IV t-PA, each with evidence of CAA. Patients with CAA may have increased risk for IV thrombolysis-associated sICH. We highlight the severe and catastrophic pattern of ICH, which may be a defining characteristic, and discuss the limitations of our current understanding of the risk of thrombolysis associated ICH in patients with CAA and/or CMBs. PMID- 26280026 TI - Epidemiological Modeling of Bovine Brucellosis in India. AB - The study objective is to develop an epidemiological model of brucellosis transmission dynamics among cattle in India and to estimate the impact of different prevention and control strategies. The prevention and control strategies are test-and-slaughter, transmission rate reduction, and mass vaccination. We developed a mathematical model based on the susceptible infectious-recovered epidemic model to simulate brucellosis transmission dynamics, calibrated to the endemically stable levels of bovine brucellosis prevalence of cattle in India. We analyzed the epidemiological benefit of different rates of reduced transmission and vaccination. Test-and-slaughter is an effective strategy for elimination and eradication of brucellosis, but socio cultural constraints forbid culling of cattle in India. Reducing transmission rates lowered the endemically stable levels of brucellosis prevalence correspondingly. One-time vaccination lowered prevalence initially but increased with influx of new susceptible births. While this epidemiological model is a basic representation of brucellosis transmission dynamics in India and constrained by limitations in surveillance data, this study illustrates the comparative epidemiological impact of different bovine brucellosis prevention and control strategies. PMID- 26280024 TI - A Review of the CD4+ T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population. AB - Childhood asthma and wheezing are very common, especially in those born preterm. Genetic and environmental factors are associated with developing asthma and wheezing. Respiratory syncytial virus and rhinovirus infections have been implicated in playing a causal role in the development of childhood asthma and wheezing, perhaps by altering the development of the immune system. Several subtypes of asthma and wheezing have been described which involve different mechanisms of pathophysiology. Much of the recent work in the field of asthma research has focused on describing unique aspects of these disease subtypes, which could lead to new drug targets. Alterations in CD4+ T cells have been described with alterations in the T helper 1, 2, 17 and regulatory cell balance could provide valuable targets for the development of new treatment strategies for the various subtypes of disease. This review article focuses on factors involved in childhood asthma and wheeze and potential drug targets. PMID- 26280027 TI - Novel ynamide structural analogues and their synthetic transformations. AB - This Highlight accounts for a recent phenomenon in which a series of novel ynamide structural analogues have emerged and caught the attention of the synthetic community. Preparations and reactions of these de novo ynamide variants are delineated here to demonstrate their accessibility as well as their reactivity. This Highlight should help reveal that these unique N-containing alkynes can become highly versatile building blocks in organic syntheses. PMID- 26280028 TI - Dielectric spectroscopy for monitoring human pancreatic islet differentiation within cell-seeded scaffolds in a perfusion bioreactor system. AB - The long-term in vitro culture and differentiation of human pancreatic islets is still hindered by the inability to emulate a suitable microenvironment mimicking physiological extracellular matrix (ECM) support and nutrient/oxygen perfusion. This is further amplified by the current lack of a non-invasive and rapid monitoring system to readily evaluate cellular processes. In this study, we realized a viable method for non-invasively monitoring isolated human pancreatic islets in vitro. Islets are induced to dedifferentiate into proliferative duct like structures (DLS) in preparation for potential and subsequent re differentiation into functional islet-like structures (ILS) in a process reminiscent of islet regeneration strategies. This long-term in vitro process is conducted within a three-dimensional microenvironment involving islets embedded in an optimized ECM gel supported by microfabricated three-dimensional scaffolds. The islet-scaffold is then housed and continuously perfused within chambers of a bioreactor platform. The process in its entirety is monitored through dielectric spectroscopy measurements, yielding an accurate representation of cellular morphology, functionality, and volume fraction. This non-invasive and real-time monitoring tool can be further manipulated to elucidate important information about the optimized cellular microenvironment required for maintaining long-term culture and achieve efficient differentiation for islet regeneration. PMID- 26280029 TI - Novel bamboo leaf shaped CuO nanorod@hollow carbon fibers derived from plant biomass for efficient and nonenzymatic glucose detection. AB - The present paper reports on the preparation of novel bamboo leaf shaped CuO nanorod dispersed hollow carbon fibers (denoted as CuO NR@PCFs). Specially, the new-type hollow carbon fibers (containing abundant micro/meso/macropores and a large specific surface area) were prepared only by simple and fast pyrolysis of the natural product catkins without using any template or surfactant. Meanwhile, a facile method was used to prepare the bamboo leaf shaped CuO nanorod covered PCFs. Thanks to the abundant micro/meso/macropores, large specific surface area, and excellent electrical conduction efficiency of the PCF matrix, the as-prepared CuO NR@PCFs could also afford more catalytic sites, show more excellent reactant transport efficiency, and display more excellent electron transport rates compared with those for the pure CuO balls. Above all, these advantages will result in the excellent oxidation and detection efficiency of the CuO NR@PCF sample to glucose. Electrochemical measurements reveal that the CuO NR@PCF modified electrode can directly catalyze glucose oxidation and display an enhanced current response compared with the pure CuO balls (such as a response time within 4 s, wide linear ranges of 5 * 10(-3)-0.8 mM and 0.8-8.5 mM, good reproducibility, considerable stability, and excellent anti-interference to electroactive molecules and Cl(-)). The superior catalytic activity and selectivity make the CuO NR@PCF catalyst very promising for application in direct detection of glucose. PMID- 26280030 TI - A polyvinyl alcohol-coated silica gel stationary phase for hydrophilic interaction chromatography. AB - Multiple layers of polyvinyl alcohol (PVA) coating are generated onto silica gel by thermal immobilization to form a stationary phase applied for hydrophilic interaction liquid chromatography (HILIC). It offers an easy way to manipulate the thickness of PVA coating and the obtained stationary phase demonstrated high efficiency and high chemical stability. PMID- 26280031 TI - Lipid-conjugated fluorescent pH sensors for monitoring pH changes in reconstituted membrane systems. AB - Accurate real-time measurements of the dynamics of proton concentration gradients are crucial for detailed molecular studies of proton translocation by membrane bound enzymes. To reduce complexity, these measurements are often carried out with purified, reconstituted enzyme systems. Yet the most paramount problem to detect pH changes in reconstituted systems is that soluble pH reporters leak out of the vesicle system during the reconstitution procedure. This requires loading of substantial amounts of pH-sensors into the lumen of unilamellar liposomes during reconstitution. Here, we report the synthesis and detailed characterisation of two lipid-linked pH sensors employing amine-reactive forms of seminaphthorhodafluors (SNARF(r)-1 dye) and rhodamine probes (pHrodoTM Red dye). Lipid-conjugation of both dyes allowed for efficient detergent-based reconstitution of these pH indicators into liposomes. Vesicle-embedded pHrodoTM displayed excellent photostability and an optimal pH-response between 4 and 7. The suitability of the lipid-linked pHrodoTM probe as a pH reporter was demonstrated by assaying the activity of a plant plasma membrane H(+)-ATPase (proton pump) reconstituted in proteoliposomes. PMID- 26280032 TI - Exploring silver ionic liquids for reaction-based gas sensing on a quartz crystal microbalance. AB - Reaction-based, sensitive sensing of aldehyde and ketone gases in real time was effectively achieved on QCM chips thin-coated with silver ionic liquids and , respectively. The method platform developed in this work involves straightforward synthesis of functional silver ionic liquids in water, and is label-free and highly chemoselective with superior gas reactivity for and and, most significantly, totally insensitive to moisture. PMID- 26280033 TI - Rhodium-catalysed alkoxylation/acetalization of diazo compounds: one-step synthesis of highly functionalised quaternary carbon centres. AB - An intermolecular tandem reaction for the rapid build-up of densely functionalised alpha-alkoxy-beta-oxo-esters has been developed. This novel process applies the easy to handle trimethyl orthoformate as a C1-building block in the rhodium(II)-catalysed alkoxylation/acetalization of donor-acceptor substituted diazo compounds. The concomitant C-O/C-C bond formation reaction gives products with unique quaternary carbon centers, substituted by groups of different oxidation level (ester, protected aldehyde and alkoxide). PMID- 26280034 TI - Light-responsive peptide [2]rotaxanes as gatekeepers of mechanised nanocontainers. AB - Novel mechanized silica nanoparticles incorporating a peptide-based molecular shuttle as a photo-responsive interlocked gatekeeper of nanocontainers are described including the uptake and delivery studies of a model cargo. PMID- 26280035 TI - The long underestimated carbonyl function of carbohydrates - an organocatalyzed shot into carbohydrate chemistry. AB - The aggressive and strong development of organocatalysis provides several protocols for the convenient utilization of the carbonyl function of unprotected carbohydrates in C-C-bond formation processes. These amine-catalyzed mechanisms enable multiple cascade-protocols for the synthesis of a wide range of carbohydrate-derived compound classes. Several, only slightly different protocols, have been developed for the application of 1,3-dicarbonyl compounds in the stereoselective chain-elongation of unprotected carbohydrates and the synthesis of highly functionalized C-glycosides of defined configuration. In addition, C-glycosides can also be accessed by amine-catalyzed reactions with methyl ketones. By a one-pot cascade reaction of isocyanides with unprotected aldoses and amino acids access to defined configured glycopeptide mimetics is achieved. Depending on the reaction conditions different origins to control the installation of configuration during the bond-formation process were observed. PMID- 26280036 TI - Alcohol research and eHealth technology. PMID- 26280037 TI - [Editorial -- we are better off than 20 years ago, and for the better]. PMID- 26280038 TI - [Is the Adenoma detection rate really of comparable quality parameters?]. PMID- 26280039 TI - [German Society of Neurosurgery and Motility -- MAGDA -- innformation forum for gastrointestinal disease]. PMID- 26280040 TI - [Hepatic encephalopathy -- flicker frequency analysis as the focal point for a structured treatment]. PMID- 26280041 TI - Preface. PMID- 26280043 TI - [Reply]. PMID- 26280044 TI - Glyco-Engineering. Preface. PMID- 26280045 TI - Proceedings and abstracts of the 15th European Meeting on Complement in Human Disease 2015, June 27-30, 2015, Uppsala, Sweden. PMID- 26280047 TI - Proceedings of the Asian Congress of Biotechnology, December 2013, New Delhi, India. PMID- 26280046 TI - Ben van der Veken honor issue. PMID- 26280048 TI - Response to Fang Fang, MB, PhD, John E. Sanderson, MD, Cheuk-man Yu, MD. PMID- 26280049 TI - Response to Ivan A. Arenas, MD, PhD, Jason Jacobson, MD, Gervasio A. Lamas, MD. PMID- 26280050 TI - In response. PMID- 26280052 TI - Proceedings of the The International Joint Meeting "GEMGERLI - From Membranes to Pathologies", November, 2013, Saint-Jean-Cap-Ferrat, France. PMID- 26280051 TI - Special issue in honor of Jun Haginaka. PMID- 26280053 TI - Special Issue: Dedicated to Arthur A. Spector, M.D. PMID- 26280054 TI - Proceedings of the Initial Meeting of the Society of Hematologic Oncology 2013, September 18-21, 2013, Houston, Texas. PMID- 26280055 TI - Special issue honoring the Life and Work of Robert B. Edgerton. PMID- 26280056 TI - Proceedings from the 34th Annual Conference of the International Society for Clinical Biostatistics, August 25-29, 2013, Munich, Germany. PMID- 26280058 TI - Proceedings of Thirteenth International Conference on Bioinformatics (InCoB2014), 31 July - 2 August, 2014, Sydney, Australia. PMID- 26280057 TI - Special issue honoring Mostafa El-Sayed. PMID- 26280059 TI - Proceedings of Thirteenth International Conference on Bioinformatics (InCoB2014), 31 July - 2 August, 2014, Sydney, Australia. PMID- 26280060 TI - Handling Parameter Uncertainty in Cost-Effectiveness Models Simply and Responsibly. PMID- 26280061 TI - William Earnshaw. PMID- 26280062 TI - Endovascular Embolization of Cerebral Arteriovenous Malformations: Results of the Japanese Registry of Neuroendovascular Therapy (JR-NET) 1 and 2. AB - This retrospective study constitutes a part of the Japanese Registry of Neuroendovascular Therapy (JR-NET) 1 and 2. Its purpose is to evaluate the feasibility, safety, and outcome of endovascular embolization for cerebral arteriovenous malformations (AVMs) in Japan. Nine hundred and eighty-seven embolization procedures were registered with JR-NET 1 and 2 (424 procedures in 122 institutions with JRNET 1 and 563 procedures in 150 institutions with JRNET 2). In total, 790 patients (80.1%) had favourable clinical outcomes defined as modified Rankin Scale (mRS) scores 0-2 at 30 days after embolization. Complete AVM obliteration by embolization alone was achieved in 90 procedures (9.1%). The procedural morbidity and mortality rate was 2.5% and 0.3% per procedure, respectively. In the multivariate logistic regression models, deep venous drainage and embolization of four or more feeding pedicles per session were significantly associated with any treatment-related complications (P=0.02 and P=0.003, respectively). About 6 cm or more in maximum nidus diameter had a negative correlation with complications (P=0.003). Our study shows that embolization of cerebral AVMs was performed with a high degree of safety and a low rate of symptomatic complications in Japan. PMID- 26280063 TI - Endovascular Embolization of Cerebral Arteriovenous Malformations: Results of the Japanese Registry of Neuroendovascular Therapy (JR-NET) 1 and 2. AB - This retrospective study constitutes a part of the Japanese Registry of Neuroendovascular Therapy (JR-NET) 1 and 2. Its purpose is to evaluate the feasibility, safety, and outcome of endovascular embolization for cerebral arteriovenous malformations (AVMs) in Japan. Nine hundred and eighty-seven embolization procedures were registered with JR-NET 1 and 2 (424 procedures in 122 institutions with JRNET 1 and 563 procedures in 150 institutions with JRNET 2). In total, 790 patients (80.1%) had favourable clinical outcomes defined as modified Rankin Scale (mRS) scores 0-2 at 30 days after embolization. Complete AVM obliteration by embolization alone was achieved in 90 procedures (9.1%). The procedural morbidity and mortality rate was 2.5% and 0.3% per procedure, respectively. In the multivariate logistic regression models, deep venous drainage and embolization of four or more feeding pedicles per session were significantly associated with any treatment-related complications (P=0.02 and P=0.003, respectively). About 6 cm or more in maximum nidus diameter had a negative correlation with complications (P=0.003). Our study shows that embolization of cerebral AVMs was performed with a high degree of safety and a low rate of symptomatic complications in Japan. PMID- 26280064 TI - Importance of polypyrrole in constructing 3D hierarchical carbon nanotube@MnO2 perfect core-shell nanostructures for high-performance flexible supercapacitors. AB - This study reports the preparation of 3D hierarchical carbon nanotube (CNT) @MnO2 core-shell nanostructures under the assistance of polypyrrole (PPy). The as prepared CNT@PPy@MnO2 core-shell structures show a perfect coating of MnO2 on each CNT and, more importantly, a robust bush-like pseudocapacitive shell to effectively increase the specific surface area and enhance the ion accessibility. As expected, a high specific capacity of 490-530 F g(-1) has been achieved from CNT@PPy@MnO2 single electrodes. And about 98.5% of the capacity is retained after 1000 charge/discharge cycles at a current density of 5 A g(-1). Furthermore, the assembled asymmetric CNT@PPy@MnO2//AC capacitors show the maximum energy density of 38.42 W h kg(-1) (2.24 mW h cm(-3)) at a power density of 100 W kg(-1) (5.83 mW cm(-3)), and they maintain 59.52% of the initial value at 10,000 W kg(-1) (0.583 W cm(-3)). In addition, the assembled devices show high cycling stabilities (89.7% after 2000 cycles for asymmetric and 87.2% for symmetric), and a high bending stability (64.74% after 200 bending tests). This ability to obtain high energy densities at high power rates while maintaining high cycling stability demonstrates that this well-designed structure could be a promising electrode material for high-performance supercapacitors. PMID- 26280065 TI - On-Surface Synthesis of BN-Substituted Heteroaromatic Networks. AB - We report on the bottom-up fabrication of BN-substituted heteroaromatic networks achieved by surface-assisted polymerization and subsequent cyclodehydrogenation of specifically designed BN-substituted precursor monomers based on a borazine core structural element. To get insight into the cyclodehydrogenation pathway and the influence of molecular flexibility on network quality, two closely related precursor monomers with different degrees of internal cyclodehydrogenation have been employed. Scanning tunneling microscopy shows that, for both monomers, surface-assisted cyclodehydrogenation allows for complete monomer cyclization and the formation of covalently interlinked BN-substituted polyaromatic hydrocarbon networks on the Ag(111) surface. In agreement with experimental observations, density functional theory calculations reveal a significantly lower energy barrier for the cyclodehydrogenation of the conformationally more rigid precursor monomer, which is also reflected in a higher degree of long-range order of the obtained heteroaromatic network. Our proof-of-concept study will allow for the fabrication of atomically precise substitution patterns within BNC heterostructures. PMID- 26280066 TI - Artificial Life Art, Creativity, and Techno-hybridization (editor's introduction). AB - Artists and engineers have devised lifelike technology for millennia. Their ingenious devices have often prompted inquiry into our preferences, prejudices, and beliefs about living systems, especially regarding their origins, status, constitution, and behavior. A recurring fabrication technique is shared across artificial life art, science, and engineering. This involves aggregating representations or re-creations of familiar biological parts-techno-hybridization but the motives of practitioners may differ markedly. This article, and the special issue it introduces, explores how ground familiar to contemporary artificial life science and engineering has been assessed and interpreted in parallel by (a) artists and (b) theorists studying creativity explicitly. This activity offers thoughtful, alternative perspectives on artificial life science and engineering, highlighting and sometimes undermining the fields' underlying assumptions, or exposing avenues that are yet to be explored outside of art. Additionally, art has the potential to engage the general public, supporting and exploring the findings of scientific research and engineering. This adds considerably to the maturity of a culture tackling the issues the discipline of artificial life raises. PMID- 26280067 TI - Emergence, Agency, and Interaction-Notes from the Field. AB - This article describes the development of several interactive installations and robotic artworks developed through the 1990s and the technological, theoretical, and discursive context in which those works arose. The main works discussed are Petit Mal (1989-1995), Sympathetic Sentience (1996-1997), Fugitive I (1996-1997), Traces (1998-1999), and Fugitive II (2001-2004)-full documentation at ( www.simonpenny.net/works ). These works were motivated by a critical analysis of cognitivist computer science, which contrasted with notions of embodied experience arising from the arts. The works address questions of agency and interaction, informed by cybernetics and artificial life. PMID- 26280068 TI - The Life of the Mimetic Starfish, 2000-2012. AB - This article is written from the perspective of the artist, programmer, and exhibitor of the Mimetic Starfish, a gestural responsive ALife artwork first created for the Millennium Dome in 2000 and recently exhibited at the Emocao Art.ficial in Brazil in 2012. The author concludes with the suggestion that despite the advances in technology and the ubiquitous presence of touch and gestural interfaces, it is the underlying aesthetic and socially engaging qualities of the Mimetic Starfish that ensure its currency, presence, relevance, and continuing exhibition. PMID- 26280069 TI - You Pretty Little Flocker: Exploring the Aesthetic State Space of Creative Ecosystems. AB - Artificial life models constitute a rich compendium of tools for the generative arts; complex, self-organizing, emergent behaviors have great interactive and generative potential. But how can we go beyond simply visualizing scientific simulations and manipulate these models for use in design and creative art contexts? You Pretty Little Flocker is a proof-of-concept study in expanding and exploring the aesthetic state space of a model for generative design. A modified version of Reynolds' flocking algorithm (1987) is described in which the space of possible images is extended and navigable in a way that at once provides user control and maintains generative autonomy. PMID- 26280070 TI - Ant- and Ant-Colony-Inspired ALife Visual Art. AB - Ant- and ant-colony-inspired ALife art is characterized by the artistic exploration of the emerging collective behavior of computational agents, developed using ants as a metaphor. We present a chronology that documents the emergence and history of such visual art, contextualize ant- and ant-colony inspired art within generative art practices, and consider how it relates to other ALife art. We survey many of the algorithms that artists have used in this genre, address some of their aims, and explore the relationships between ant- and ant-colony-inspired art and research on ant and ant colony behavior. PMID- 26280071 TI - Accretor: Generative Materiality in the Work of Driessens and Verstappen. AB - Accretor, by the Dutch artists Erwin Driessens and Maria Verstappen, is a generative artwork that adopts and adapts artificial life techniques to produce intricate three-dimensional forms. This article introduces and analyzes Accretor, considering the enigmatic quality of the generated objects and in particular the role of materiality in this highly computational work. Accretor demonstrates a tangled continuity between digital and physical domains, where the constraints and affordances of matter inform both formal processes and aesthetic interpretations. Drawing on Arp's notion of the concrete artwork and McCormack and Dorin's notion of the computational sublime, the article finally argues that Accretor demonstrates what might be called a processual sublime, evoking expansive processes that span both computational and non-computational systems. PMID- 26280072 TI - Living Poetry. AB - We introduce three of our interactive artworks that translate text into artificial creatures or creatures into text by means of user interaction. These installations make use of experimental literature, media archaeology, surrealism, artificial life, and algorithmic methods. PMID- 26280073 TI - On Writing and Reading Artistic Computational Ecosystems. AB - We study the use of the generative systems known as computational ecosystems to convey artistic and narrative aims. These are virtual worlds running on computers, composed of agents that trade units of energy and emulate cycles of life and behaviors adapted from biological life forms. In this article we propose a conceptual framework in order to understand these systems, which are involved in processes of authorship and interpretation that this investigation analyzes in order to identify critical instruments for artistic exploration. We formulate a model of narrative that we call system stories (after Mitchell Whitelaw), characterized by the dynamic network of material and conceptual processes that define these artefacts. They account for narrative constellations with multiple agencies from which meaning and messages emerge. Finally, we present three case studies to explore the potential of this model within an artistic and generative domain, arguing that this understanding expands and enriches the palette of the language of these systems. PMID- 26280074 TI - Performative Apparatus and Diffractive Practices: An Account of Artificial Life Art. AB - Drawing on our own art/science practices and a series of interviews with artificial life practitioners, we explore the entanglement of developments at the artistic edges of artificial life. We start by defining key terms from Karen Barad's agential realism. We then diffractively read artificial life together with agential realism to discuss the potential for interventions in the field. Through a discussion of artificial life computer simulations, ideas of agency are problematized, and artificial life's single purposeful actor, the agent, is replaced by agential, an adjective denoting a relationship rather than a subject object duality. We then seek to reinterpret the difficult-to-define term "emergence." Agency in artificial life emerges through what Barad calls entanglement, in this case between observers and their apparatus, a perpetual engagement between observations of a system and their interpretations. The article explores the differences that this diffractive perspective makes to artificial life and accounts of its materialization. PMID- 26280075 TI - Theater and ALife Art: Modeling Open and Closed Systems. AB - The live art of theater remains curiously missing from ALife art history, despite the fact that its very existence is poised on the cusp of the living and the artificial, and on the modeling of life as artefact-what can be called the containment-versus-continuity dilemma. How far one seeks to affirm autonomy of the creative artwork or, in contrast, how far one seeks to affirm its continuity with its supposed real-life contexts is a question that has forever haunted theater, and that has naturally come to haunt ALife and ALife arts. Investigation of the boundary separating observers from modeled systems is as core to research into the live art of theater as to ALife research. This brief article seeks to open up discussion on links between ALife, ALife art, and the live art of theater, through key thematic threads that traverse these domains: their modeling of universes, the open or closed nature of the resultant modeled systems, and their implications with respect to observers, definitions, and instantiations of life regarding non-life or death as well as attributions of liveness to emergent synthetic biology and metamaterials. PMID- 26280076 TI - Creativity and ALife. AB - Three forms of creativity are exemplified in biology and studied in ALife. Combinational creativity exists as the first step in genetic algorithms. Exploratory creativity is seen in models using cellular automata or evolutionary programs. Transformational creativity can result from evolutionary programming. Even radically novel forms can do so, given input from outside the program itself. Transformational creativity appears also in reaction-diffusion models of morphogenesis. That there are limits to biological creativity is suggested by ALife work bearing on instances of biological impossibility. PMID- 26280077 TI - Computational Social Creativity. AB - This article reviews the development of computational models of creativity where social interactions are central. We refer to this area as computational social creativity. Its context is described, including the broader study of creativity, the computational modeling of other social phenomena, and computational models of individual creativity. Computational modeling has been applied to a number of areas of social creativity and has the potential to contribute to our understanding of creativity. A number of requirements for computational models of social creativity are common in artificial life and computational social science simulations. Three key themes are identified: (1) computational social creativity research has a critical role to play in understanding creativity as a social phenomenon and advancing computational creativity by making clear epistemological contributions in ways that would be challenging for other approaches; (2) the methodologies developed in artificial life and computational social science carry over directly to computational social creativity; and (3) the combination of computational social creativity with individual models of creativity presents significant opportunities and poses interesting challenges for the development of integrated models of creativity that have yet to be realized. PMID- 26280078 TI - Studying Collective Human Decision Making and Creativity with Evolutionary Computation. AB - We report a summary of our interdisciplinary research project "Evolutionary Perspective on Collective Decision Making" that was conducted through close collaboration between computational, organizational, and social scientists at Binghamton University. We redefined collective human decision making and creativity as evolution of ecologies of ideas, where populations of ideas evolve via continual applications of evolutionary operators such as reproduction, recombination, mutation, selection, and migration of ideas, each conducted by participating humans. Based on this evolutionary perspective, we generated hypotheses about collective human decision making, using agent-based computer simulations. The hypotheses were then tested through several experiments with real human subjects. Throughout this project, we utilized evolutionary computation (EC) in non-traditional ways-(1) as a theoretical framework for reinterpreting the dynamics of idea generation and selection, (2) as a computational simulation model of collective human decision-making processes, and (3) as a research tool for collecting high-resolution experimental data on actual collaborative design and decision making from human subjects. We believe our work demonstrates untapped potential of EC for interdisciplinary research involving human and social dynamics. PMID- 26280079 TI - Toxicity mechanisms of ionic silver and polymer-coated silver nanoparticles with interactions of functionalized carbon nanotubes on early development stages of sea urchin. AB - Exposures of aquatic organisms to multiple contaminants are likely to take place in estuarine and coastal areas and combined effects on early life stages have to be examined. Among emerging contaminants, ionic silver (Ag(+)) and silver nanoparticles (AgNps) have demonstrated contrasting effects on marine invertebrates, but their interactions with functionalized carbon nanotubes (f SWCNTs) have not yet been investigated in details. In order to observe the impacts and understand the toxicity mechanism of Ag(+) and polymer-coated AgNps, and their combined effects with f-SWCNTs, successive development stages of embryos of sea urchin, Strongylocentrotus droebachiensis, were exposed to Ag(+), AgNps and f-SWCNTs, separately and in mixtures using moderate environmental concentrations. We also assessed long-term effects of treatments under recovery conditions. Morphological endpoints such as archenteron elongation, primary and secondary mesenchyme cells fate, pigment cells migration, spiculogenic cells and gut development indicated different effects of silver and nanosilver forms during successive development stages. Whereas Ag(+) induced vegetalization and extrusion of mesenchyme cells on early embryos; f-SWCNTs+Ag(+) strongly interfered with gut regionalization in late larvae. Sensitive blastocoelar cells got vacuolized and shapeless with AgNps, but not with mixtures with f-SWCNTs. Increased concentrations of Ag(+) and f-SWCNTs+Ag(+) led to the most disruptive effects during development, but f-SWCNTs+Ag(+) caused the highest mortality rate during the recovery period, which indicated far-reaching effects driven by f-SWCNTs and their ability to keep silver more available during exposure period. PMID- 26280080 TI - Assessment of hematologic parameters before and after bimaxillary orthognathic surgery. AB - PURPOSE: The purpose of the study was to evaluate changes of hematologic parameters in bimaxillary surgery. METHODS: Fifty-three patients were prospectively evaluated and divided into groups based on the surgical procedure and sex (predictor variables). Hemoglobin, red blood cells, hematocrit, and platelet were the primary outcome variables, operation time the secondary outcome, and the patients' age and weight the other variables. TRIAL REGISTRATION: NCT02364765 (U.S. National Institutes of Health, clinicaltrials.gov). RESULTS: There was statistically significant difference between all hematologic parameters before and after surgery, for both men and women, and for all surgical groups. There was a positive correlation between operative time and the decrease (in %) of the hematologic parameters. Linear regression analysis suggested that the Hb values decrease 0.083 % for every minute increase in the operation time, and 0.066, 0.066, and 0.010 % for RBC, Hct, and platelet count, respectively. There was a negative correlation between weight and all hematologic parameters. Correlations between age and hematologic parameters were not statistically significant. Almost all correlations between age, weight, sex, and the surgery group and the hematologic parameters were considered as very weak. Only one patient was transfused. CONCLUSIONS: It is suggested that operation time and patient's weight play a bigger role than patient's age and sex in the decrease of hematologic parameters after bimaxillary surgery. PMID- 26280081 TI - BTK gene targeting by homologous recombination using a helper-dependent adenovirus/adeno-associated virus hybrid vector. AB - X-linked agammaglobulinemia (XLA) is one of the most common humoral immunodeficiencies, which is caused by mutations in Bruton's tyrosine kinase (BTK) gene. To examine the possibility of using gene therapy for XLA, we constructed a helper-dependent adenovirus/adeno-associated virus BTK targeting vector (HD-Ad.AAV BTK vector) composed of a genomic sequence containing BTK exons 6-19 and a green fluorescence protein-hygromycin cassette driven by a cytomegalovirus promoter. We first used NALM-6, a human male pre-B acute lymphoblastic leukemia cell line, as a recipient to measure the efficiency of gene targeting by homologous recombination. We identified 10 clones with the homologous recombination of the BTK gene among 107 hygromycin-resistant stable clones isolated from two independent experiments. We next used cord blood CD34+ cells as the recipient cells for the gene targeting. We isolated colonies grown in medium containing cytokines and hygromycin. We found that the targeting of the BTK gene occurred in four of the 755 hygromycin-resistant colonies. Importantly, the gene targeting was also observed in CD19+ lymphoid progenitor cells that were differentiated from the homologous recombinant CD34+ cells during growth in selection media. Our study shows the potential for the BTK gene therapy using the HD-Ad.AAV BTK vector via homologous recombination in hematopoietic stem cells. PMID- 26280082 TI - The targeted inhibitory effects of human amniotic fluid stem cells carrying CXCR4 promoter and DAL-1 on non-small cell lung carcinoma growth. AB - The differentially expressed in adenocarcinoma of the lung-1 (DAL-1) protein has been demonstrated to be suppressive to various types of tumors including lung cancer. This study aimed to determine the targeted effects of human amniotic fluid stem cells (hAFS cells) carrying CXCR4 promoter driven conditionally replicable adenovirus vector overexpressing DAL-1 (Ad-CXCR4-DAL-1) on non-small cell lung carcinoma (NSCLC) growth. The apoptotic effects of virus vectors were assessed using flow cytometry, and the cytotoxicity analyzed by CCK-8 assay. In vivo imaging system was used to determine the homing capability of hAFS cells. A549 cell xenograft mouse model was created to assess the in vivo effect of DAL-1 overexpression on NSCLC growth. We found that infection of Ad-CXCR4-DAL-1 increased the apoptosis of A549 NSCLC cells but not 16HBE normal human bronchial epithelial cells. Ad-CXCR4-DAL-1 administered via intratumoral injection led to significant reduced growth and greater necrosis of A549 xenograft tumors comparing to null vector treated animals. When infused via tail vein, hAFS cells carrying Ad-CXCR4-DAL-1 homed to lung cancer xenografts, caused virus replication and DAL-1 overexpression, and led to significant lower growth and greater necrosis of A549 cell xenografts comparing to non-treatment control. In conclusion, hAFS cells are capable of carrying Ad-CXCR4-DAL-1 vectors, specifically targeting to lung cancer, and causing oncolytic effects when administered in vivo. PMID- 26280083 TI - MTBP Promotes the Invasion and Metastasis of Hepatocellular Carcinoma by Enhancing the MDM2-Mediated Degradation of E-Cadherin. AB - BACKGROUND: Emerging evidence suggests that MTBP plays a role in cancer development and possibly progression, but its influence on hepatocellular carcinoma (HCC) remains unclear. METHODS: We used real-time PCR and Western blotting to investigate MTBP expression in four HCC cell lines, 120 pairs of tumor and corresponding paracarcinomatous tissues from HCC patients. Immunohistochemistry was performed to examine MTBP expression in HCC and corresponding paracarcinomatous tissues from 120 patients. E-cadherin was only examined in HCC tissues of patients mentioned above. Statistical analyses were applied to evaluate the prognostic value and associations of MTBP expression with clinical parameters. Furthermore, the MTBP gene was overexpressed in HepG2 cell and silenced by siRNA in Hu7 cell, and cell migration and invasion were detected in vitro and in vivo. Moreover, the molecular mechanism of E-cadherin regulation by MTBP was explored. RESULTS: In this study, we first showed that MTBP protein expression is positively correlated with distant metastasis and poor prognosis in HCC patients. We also found that MTBP expression was increased in metastatic cell lines when compared with nonmetastatic cell lines. Consistent with these findings, enhanced expression of MTBP promoted HCC cell invasiveness and metastasis both in vitro and in vivo, whereas the knockdown of MTBP with small interfering RNA resulted in reduced HCC migration and invasion. Ectopic expression of MTBP in HCC cells induced epithelial-to-mesenchymal transition, whereas the silencing of MTBP had the opposite effect. Furthermore, our results show that MTBP and E-cadherin protein expression are inversely correlated in primary HCC tissues. Moreover, our findings indicate that MTBP overexpression decreases E-cadherin expression through the modulation of Mdm2 ubiquitination degradation. CONCLUSIONS: Our data show that MTBP aggravates the invasion and metastasis of HCC by promoting the MDM2-mediated degradation of E-cadherin. PMID- 26280084 TI - Gastric Electric Stimulation for Refractory Gastroparesis: A Prospective Analysis of 151 Patients at a Single Center. AB - BACKGROUND: Gastric electric stimulation (GES) is used to treat patients with refractory gastroparesis symptoms. However, the effectiveness of GES in clinical practice and the effect of GES on specific symptoms of gastroparesis are not well delineated. AIMS: To determine the effectiveness of GES for treatment for refractory symptoms of gastroparesis, the improvement in specific symptoms of gastroparesis, and clinical factors impacting on outcome. METHODS: Enterra GES was used to treat refractory gastroparesis symptoms. Patients filled out a symptom severity questionnaire (PAGI-SYM) prior to insertion. At each follow-up visit, the patient filled out PAGI-SYM and assessed their therapeutic response using the Clinical Patient Grading Assessment Scale (CPGAS). RESULTS: One hundred and fifty-one patients (120 females) with refractory gastroparesis (72 diabetic, 73 idiopathic, 6 other) underwent GES. Of the 138 with follow-up (1.4 +/- 1.0 years), the average CPGAS was 2.4 +/- 0.3 (SEM): 104 patients (75 %) improved (CPGAS > 0) and 34 (25 %) did not (CPGAS <= 0). Sixty patients (43 %) were at least moderately improved (CPGAS score >=4). Clinical improvement was seen in both diabetic and idiopathic patients with the CPGAS in diabetic patients (3.5 +/ 0.3) higher in idiopathic patients (1.5 +/- 0.5; p < 0.05). Symptoms significantly improving the most included nausea, loss of appetite, and early satiety. Vomiting improved in both diabetic and idiopathic patients although the diabetic subgroup experienced a significantly greater reduction in vomiting than the idiopathic subgroup. CONCLUSIONS: In this cohort of patients with refractory gastroparesis, GES improved symptoms in 75 % of patients with 43 % being at least moderately improved. Response in diabetics was better than in nondiabetic patients. Nausea, loss of appetite, and early satiety responded the best. PMID- 26280085 TI - Gastric Electrical Stimulation and Sacral Electrical Stimulation: A Long-Term Follow-Up Study of Dual-Device Treatment. AB - AIMS: The objective of this study was to investigate sacral electrical stimulation (SES) and gastric electrical stimulation (GES) by comparing upper and lower gastrointestinal (GI) and genitourinary (GU) symptoms and quality of life, before treatment and in the long term after treatment. We hypothesized that dual device treatment would greatly improve upper and lower gastrointestinal and genitourinary symptoms, as well as quality of life. METHODS: Fifty-four patients who underwent dual-device treatment (GES and SES) were enrolled in this study. Patients who had surpassed 24 months since the second-device insertion were included. Patients were evaluated before and after both devices were implanted and given a symptom questionnaire regarding their upper GI, lower GI, and GU symptoms and their quality of life. RESULTS: With combined treatment, a statistically significant improvement was seen in upper GI, lower GI, and GU symptoms and quality of life. However, fecal incontinence and fecal urgency improvements did not reach statistical significance, likely due to the small sample size. CONCLUSION: The implantation of two stimulators appears to be safe and effective to improve patients' quality of life for those with upper GI symptoms, bowel problems, and bladder dysfunction. PMID- 26280086 TI - Genetic characterization of livestock and human hydatid cyst isolates from northwest Iran, using the mitochondrial cox1 gene sequence. AB - Cystic echinococcosis (CE), caused by larval stages of the tapeworm Echinococcus granulosus, is one of the most important zoonoses distributed worldwide. Genotype analysis of the parasite isolates from various hosts is required to better understand the host specificity and transmission routes. The aim of this study was to identify the genotypes of E. granulosus isolated from humans and domestic animals from northwest of Iran (Zanjan Province) using the mitochondrial cox1 gene sequence. A total of 86 hydatid cysts including 49 sheep and 28 cattle isolates from the slaughterhouse and nine human isolates from surgical wards of local hospitals were collected. The isolates were subjected to DNA extraction, PCR amplification, and sequence. Eighty-two (95.35 %) isolates, including 47 sheep, 26 cattle, and all nine human isolates, were determined as G1 genotype, and the remaining four (4.65 %), including two sheep and two cattle isolates, were identified as G3 genotype. From the cox1 sequence data, 13 different haplotypes (10 G1s and three G3s) were detected and named as EGH1-EGH13 (GenBank accession numbers, KP859559-KP859571). EGH1 was the major variant among the haplotypes, and it was identified in 46 (53.49 %) isolates (31 sheep, 14 cattle, and one human). Alignment of the partial cox1 sequences showed 12 point mutations including seven (58.3 %) synonymous and five (41.7 %) non-synonymous substitutions. Based on the results, G1 was the major genotype of E. granulosus in northwest of Iran affecting sheep, cattle, and humans. In addition, a minor group of G3 genotype was found to be circulating in this region. PMID- 26280088 TI - [Understanding more from the ECG]. PMID- 26280087 TI - Extended O-GlcNAc on HLA Class-I-Bound Peptides. AB - We report unexpected mass spectrometric observations of glycosylated human leukocyte antigen (HLA) class I-bound peptides. Complemented by molecular modeling, in vitro enzymatic assays, and oxonium ion patterns, we propose that the observed O-linked glycans carrying up to five monosaccharides are extended O GlcNAc's rather than GalNAc-initiated O-glycans. A cytosolic O-GlcNAc modification is normally terminal and does not extend to produce a polysaccharide, but O-GlcNAc on an HLA peptide presents a special case because the loaded HLA class I complex traffics through the endoplasmic reticulum and Golgi apparatus on its way to the cell membrane and is hence exposed to glycosyltransferases. We also report for the first time natural HLA class I presentation of O- and N-linked glycopeptides derived from membrane proteins. HLA class I peptides with centrally located oligosaccharides have been shown to be immunogenic and may thus be important targets for immune surveillance. PMID- 26280089 TI - O,N,B-Containing eight-membered heterocycles by ring expansion of boroles with nitrones. AB - By a ring expansion reaction of boroles with nitrones a straightforward route to eight-membered O,N,B-containing ring systems was developed, which present a new structural motif in heterocyclic chemistry. Formally, these compounds can be considered as BN-analogues of eight-membered ring ethers containing three double bonds. The X-ray crystallographic data of a series of these oxazaborocine derivatives show that they adopt a boat conformation in the solid state. PMID- 26280090 TI - The effects of Kv1.3 and IKCa1 channel inhibition on cytokine production and calcium influx of T lymphocytes in rheumatoid arthritis and ankylosing spondylitis. AB - Kv1.3 and IKCa1 lymphocyte potassium channels have been implicated as important targets of selective immunomodulation. We compared the alterations in cytokine production upon selective inhibition of Kv1.3 or IKCa1 channels (by MGTX and TRAM, respectively) in healthy donors (HD), RA and AS patients. We also determined calcium influx kinetics and its sensitivity to Kv1.3 and IKCa1 channel inhibition following PHA activation in CD4, Th1, Th2 and CD8 cells as well as monocytes. The application of TRAM resulted in a lower production of TNF-a and IL1-RA in all three study groups. Inhibition by TRAM had contrary effects on the production of IL-1b and IL-5: While their production was increased by PBMCs of RA patients, this effect was not observed in HD and AS PBMCs. While treatment with MGTX resulted in a similar decrease in calcium influx in the CD4 and Th2 subsets across all study groups, TRAM treatment had opposite effects on RA and HD samples: It decreased calcium influx in the Th2 and CD8 subsets in RA, while only Th1 cells were affected in HDs. The effects of IKCa1 channel inhibition are controversial in samples of RA and AS patients, since it shifts the inflammatory balance into the pro-inflammatory direction. PMID- 26280091 TI - A diagnosis of the microbiological quality of dehydrated bee-pollen produced in Brazil. AB - Bee-pollen is an apicultural product with potential for medical and nutritional applications; therefore, its microbiology quality should be monitored. In this context, the objective of this study was to diagnose the microbiological quality of 45 dehydrated bee-pollen samples collected from November 2011 to December 2013 in nine Brazilian States. All the samples were negative for sulphite-reducing Clostridium spores, Salmonella, coagulase-positive Staphylococcus and Escherichia coli, which are micro-organisms of public health concern. Total aerobic mesophilic micro-organism counts ranged from <10 to 1.10 * 10(4) CFU g(-1) , with psychrotroph counts ranging from <10 to 1.12 * 10(3) CFU g(-1) and total coliforms from <10 to 2.80 * 10(3) CFU g(-1) , while the values for yeasts and moulds were between <10 to 7.67 * 10(3) CFU g(-1) . According to the literature, the microbiota observed in this study were typical; however, it is important to consider that these micro-organisms may cause spoilage and diminish shelf life, reason by which quality control programs should be implemented. SIGNIFICANCE AND IMPACT OF THE STUDY: Contamination of bee-pollen can occur during production, collection and processing, but there are few studies of the microbiological quality of this product. Brazil is an important producer of dehydrated bee pollen, therefore, a diagnosis of the microbiological status is important to ensure the safety of many consumers. Salmonella sp., genus Clostridium, coagulase positive Staphylococcus, Escherichia coli and even some yeast species are micro organisms of public health concern and their presence must be monitored. Furthermore, the determination of spoilage micro-organisms indicates whether the production and the processing practices carried out by beekeepers and warehouses were adequate. PMID- 26280092 TI - Effect of Florida's Prescription Drug Monitoring Program and Pill Mill Laws on Opioid Prescribing and Use. AB - IMPORTANCE: Prescription Drug Monitoring Program (PDMP) and pill mill laws are among the principal means states use to reduce prescription drug abuse and diversion, yet little high-quality evidence exists regarding their effect. OBJECTIVE: To quantify the effect of Florida's PDMP and pill mill laws on overall and high-risk opioid prescribing and use. DESIGN, SETTING, AND PARTICIPANTS: We applied comparative interrupted time-series analyses to IMS Health LifeLink LRx data to characterize the effect of PDMP and pill mill law implementation on a closed cohort of prescribers, retail pharmacies, and patients from July 2010 through September 2012 in Florida (intervention state) compared with Georgia (control state). We conducted sensitivity analyses, including varying length of observation and modifying requirements for continuous observation of individuals throughout the study period. MAIN OUTCOMES AND MEASURES: Total opioid volume, mean morphine milligram equivalent (MME) per transaction, mean days' supply per transaction, and total number of opioid prescriptions dispensed. Analyses were conducted per prescriber and per patient, in aggregate and after stratifying by volume of baseline opioid prescribing for prescribers and use for patients. RESULTS: From July 2010 through September 2012, a cohort of 2.6 million patients, 431,890 prescribers, and 2829 pharmacies was associated with approximately 480 million prescriptions in Florida and Georgia, 7.7% of which were for opioids. Total monthly opioid volume, MME per transaction, days' supply, and prescriptions dispensed were higher in Florida than Georgia before implementation. Florida's laws were associated with statistically significant declines in opioid volume (2.5 kg/mo, P<.05; equivalent to approximately 500,000 5-mg tablets of hydrocodone bitartrate per month) and MME per transaction (0.45 mg/mo, P<.05), without any change in days' supply. Twelve months after implementation, the policies were associated with approximately a 1.4% decrease in opioid prescriptions, 2.5% decrease in opioid volume, and 5.6% decrease in MME per transaction. Reductions were limited to prescribers and patients with the highest baseline opioid prescribing and use. Sensitivity analyses, varying time windows, and enrollment criteria supported the main results. CONCLUSIONS AND RELEVANCE: Florida's PDMP and pill mill laws were associated with modest decreases in opioid prescribing and use. Decreases were greatest among prescribers and patients with the highest baseline opioid prescribing and use. PMID- 26280093 TI - Development of Smart Semisolid Formulations to Enhance Retinoic Acid Topical Application. AB - Retinoids play a very important role in the topical treatment of acne vulgaris. However, their use is restricted because of the limited photostability responsible for local adverse effects as erythema, dryness, itching, and stinging. In this way, the therapeutic efficacy of such molecules is strongly reduced, resulting, at the same time, harmful for the patient upon light exposure. Thus, a suitable technological strategy is necessary to increase retinoid stability in order to have a product both safe and efficacious. With this aim, new inorganic-organic hybrids based on tretinoin (retinoic acid, RET) and hydrotalcite-like compounds (HTlc) have been prepared and well characterized by X-ray powder diffraction, inductively coupled plasma spectrometry, thermal analyses, scanning electron microscopy, and UV-Vis spectrophotometric measurements. Such hybrids, namely, ZnAl-HTlc-RET and MgAl-HTlc-RET, were formulated as simple gels for topical use and submitted to further studies in order to evaluate their rheological properties, photostability, and RET release capability. The RET photostability resulted improved upon intercalation into HTlc, both in MgAl-HTlc and ZnAl-HTlc, as proved by the data acquired during irradiation of the sample at 366 nm. This strategy is suitable for the realization of safe, efficacious, and compliant topical formulations for acne treatment. PMID- 26280094 TI - Improving Dermatological Care for Elderly People Living in Permanent Healthcare Institutions: Suggestions from Dutch Dermatologists. PMID- 26280095 TI - Continuous feelings of love? The parental bond from pregnancy to toddlerhood. AB - Both prenatal and postnatal parental bonding (i.e., the affective tie from parent to child) have important effects on parental and child functioning. However, research on the continuity and correlates of parental bonding is lacking. Therefore, the goal of the present study was to examine the stability of bonding levels and to explore distinct bonding patterns with a latent class analysis. Moreover, the correlates of these bonding patterns in the parental-, child-, and contextual domain were studied. Levels of maternal (N = 370) and paternal (N = 292) bonding and potential correlates were assessed at 26 weeks of pregnancy, 6 months, and 24 months postpartum. Results showed moderate stability of bonding from pregnancy to toddlerhood. For both mothers and fathers, 4 distinct bonding patterns were found. Parents with low bonding patterns were characterized by increased anxiety and parenting stress, less partner support, less adaptive personality profiles, and children with difficult temperament. These findings indicate the importance of monitoring young children's parents with poor levels of bonding as their bonding patterns remain stable from pregnancy until toddlerhood and because those parents experience problems in multiple domains. PMID- 26280096 TI - Bile canalicular dynamics in hepatocyte sandwich cultures. AB - Many substances are hepatotoxic due to their ability to cause intrahepatic cholestasis. Therefore, there is a high demand for in vitro systems for the identification of cholestatic properties of new compounds. Primary hepatocytes cultivated in collagen sandwich cultures are known to establish bile canaliculi which enclose secreted biliary components. Cholestatic compounds are mainly known to inhibit bile excretion dynamics, but may also alter canalicular volume, or hepatocellular morphology. So far, techniques to assess time-resolved morphological changes of bile canaliculi in sandwich cultures are not available. In this study, we developed an automated system that quantifies dynamics of bile canaliculi recorded in conventional time-lapse image sequences. We validated the hepatocyte sandwich culture system as an appropriate model to study bile canaliculi in vitro by showing structural similarity measured as bile canaliculi length per hepatocyte to that observed in vivo. Moreover, bile canalicular excretion kinetics of CMFDA (5-chloromethylfluorescein diacetate) in sandwich cultures resembled closely the kinetics observed in vivo. The developed quantification technique enabled the quantification of dynamic changes in individual bile canaliculi. With this technique, we were able to clearly distinguish between sandwich cultures supplemented with dexamethasone and insulin from control cultures. In conclusion, the automated quantification system offers the possibility to systematically study the causal relationship between disturbed bile canalicular dynamics and cholestasis. PMID- 26280097 TI - Pretreatment by NaOH swelling and then HCl regeneration to enhance the acid hydrolysis of cellulose to glucose. AB - A simple pretreatment method, NaOH swelling at a low temperature and then HCl regeneration, was developed for depolymerization of cellulose to glucose. Cellulose was transformed into amorphous hydrogel during the treatment; and due to the easy diffusion of H(+) and Cl(-) ions into the cellulose hydrogel network as well as the strong ability of Cl(-) to disrupt the massive hydrogen bond, the hydrolysis rate was greatly enhanced. The method is effective for alpha cellulose, microcrystalline cellulose, filter paper, ramie fiber and absorbent cotton. Even at a high alpha-cellulose concentration of 50g/L, 29.1% yield of glucose was still obtained within 10min at 160 degrees C under microwave irradiation, where up to 16.2g/L of glucose solution was given. The influence of NaOH concentration, HCl concentration, hydrolysis temperature and time on the hydrolysis rate was investigated. The structure of cellulose hydrogel was also studied to confirm the reaction mechanism. PMID- 26280098 TI - Exploration of using stripped ammonia and ash from poultry litter for the cultivation of the cyanobacterium Arthrospira platensis and the green microalga Chlorella vulgaris. AB - Herein a new approach of exploiting poultry litter (PL) is demonstrated. The suggested method includes drying of PL with simultaneously striping and recovery of ammonia, followed by the direct combustion of dried PL. The generated ash after the combustion, and the striped ammonia consequently, could be used as nutrient source for the cultivation of microalgae or cyanobacteria to produce feed additives. The present study explored the application of PL ash and recovered ammonia for the cultivation of Arthrospira platensis and Chlorella vulgaris. For a simultaneously 90% dissolution of ash potassium and phosphorus, a ratio of acid to ash of 0.02mol-H(+)/g was required. The optimum mass of ash required was 0.07-0.08g/g dry biomass, while the addition of ammoniac nitrogen of 8-9mgN per g of dry biomass per day was adequate for a satisfactory production of A. platensis and C. vulgaris. PMID- 26280099 TI - Application of orange peel waste in the production of solid biofuels and biosorbents. AB - This work aimed to study the potential use of pyrolyzed orange peels as solid biofuels and biosorption of heavy metals. The dry biomass and the biofuel showed moderate levels of carbon (44-62%), high levels of oxygen (30-47%), lower levels of hydrogen (3-6%), nitrogen (1-2.6%), sulfur (0.4-0.8%) and ash with a maximum of 7.8%. The activation energy was calculated using Kissinger method, involving a 3 step process: volatilization of water, biomass degradation and volatilization of the degradation products. The calorific value obtained was 19.3MJ/kg. The studies of metal biosorption based on the Langmuir model obtained the best possible data fits. The results obtained in this work indicated that the potential use of waste orange peel as a biosorbent and as a solid biofuel are feasible, this product could be used in industrial processes, favoring the world economy. PMID- 26280100 TI - Biorefineries based on coffee cut-stems and sugarcane bagasse: furan-based compounds and alkanes as interesting products. AB - This work presents a techno-economic and environmental assessment for a biorefinery based on sugarcane bagasse (SCB), and coffee cut-stems (CCS). Five scenarios were evaluated at different levels, conversion pathways, feedstock distribution, and technologies to produce ethanol, octane, nonane, furfural, and hydroxymethylfurfural (HMF). These scenarios were compared between each other according to raw material, economic, and environmental characteristics. A single objective function combining the Net Present Value and the Potential Environmental Impact was used through the Analytic Hierarchy Process approach to understand and select the best configurations for SCB and CCS cases. The results showed that the configuration with the best economic and environmental performance for SCB and CCS is the one that considers ethanol, furfural, and octane production (scenario 1). The global economic margin was 62.3% and 61.6% for SCB and CCS respectively. The results have shown the potential of these types of biomass to produce fuels and platform products. PMID- 26280101 TI - Rapid and Quantitative Detection of Avian Influenza A(H7N9) Virions in Complex Matrices Based on Combined Magnetic Capture and Quantum Dot Labeling. AB - Avian influenza A(H7N9) virus, which emerged in China in the spring of 2013, has infected hundreds of people and resulted in many deaths. Herein, a rapid and quantitative assay is proposed for the one-step detection of H7N9 virions. Immunomagnetic nanospheres (IMNs) and antibody-conjugated quantum dots (Ab-QDs) are simultaneously employed to capture and identify the target virus, leading to a high efficiency, good specificity, and strong anti-interference ability. Moreover, this reliable detection assay, which combines the efficient magnetic enrichment and the unique photophysical properties of QDs, can achieve a high sensitivity for a low detection limit. At the same time, this detection strategy shows great flexibility for employment in a variety of fluorescence detectors, including fluorescence spectrometry, microscope assays, and handheld UV lamp tests. Furthermore, our one-step detection strategy induces very little change in the integrity of the vulnerable virions, which enables additional genotyping testing following the fluorescence detection. The present study, thus, reports a rapid and quantitative approach for the detection of H7N9 virions based on simultaneous magnetic capture and QD labeling, thereby providing a higher probability for detection and therefore faster diagnosis of H7N9-infected patients. PMID- 26280104 TI - Unusual Intramolecular Hydrogen Transfer in 3,5-Di(triphenylethylenyl) BODIPY Synthesis and 1,2-Migratory Shift in Subsequent Scholl Type Reaction. AB - The straightforward synthesis of 3,5-di(triphenylethylenyl) BODIPYs 1-3 from the condensation of 2-(triphenylethylenyl) pyrrole with aryl aldehydes are surprisingly found to produce side products that are hydrogenated at one of the two triphenylethylene substituents. It was also observed that the subsequent Scholl type reaction of 1 resulted in a "1,2-migratory shift" of one triphenylethylene substituent in addition to a ring closing reaction. Preliminary investigations, including DFT calculations and isolation of intermediates, were conducted to study these unusual observations on BODIPY chemistry. PMID- 26280103 TI - A Systematic Research Review Assessing the Effectiveness of Pursuit Interventions in Spatial Neglect Following Stroke. AB - Rehabilitation after stroke is imperative for patients with spatial neglect as it can help improve behavioural, social and cognitive outcomes in these patients, and therefore reduce the financial burden on public health services. The main aim of this review is to investigate the effectiveness of active pursuit eye movements for rehabilitation interventions in patients with spatial neglect following stroke. Potential papers for inclusion were gathered by searching key terms in four main databases (AMED, Global Health, PubMed/Medline and PsychInfo) in addition to screening relevant reference lists. Two reviewers independently selected papers for inclusion based on agreed inclusion criteria (n = 9 with 147 participants). Risk of bias was assessed using the QUADAS-2 tool. All papers reported a statistically significant result in patients who received an intervention which used pursuit eye movements, and this was reported both as a short-term (immediate) effect and as a sustained effect up to 8 weeks after treatment. These effects were also reported in comparison with interventions using saccadic eye movements. One study also reported increased neural activity in a number of brain regions following pursuit-based intervention. Overall, there is good evidence in support of pursuit intervention used in the rehabilitation of stroke and spatial neglect over and above traditional interventions based on saccadic eye movements. Future research should aim to increase sample sizes, provide information on statistical power, record accurate eye movement responses and use randomised designs to reduce selection bias. PMID- 26280105 TI - Life Stressors and Posttraumatic Stress Disorder in a Seriously Mentally Ill Jail Population. AB - Inmates represent a vulnerable population with increased rates of trauma and posttraumatic stress disorder (PTSD). However, little is known about the rates of trauma and PTSD among male inmates with acute psychiatric illness. This prospective, randomized study was conducted to assess the current rates of trauma and PTSD in this population. The sample consisted of 48 patients admitted to a hospital jail psychiatry service in New York City. Subjects were administered the Life Stressor Checklist-Revised and the Structured Clinical Interview for DSM-IV TR Disorders, PTSD Module (SCID-I). The rate of PTSD diagnosis via SCID-I was 46.2% as compared to 2.1% diagnosis via clinical interview. All participants reported a history of at least one stressful and/or traumatic event, and many of these events occurred during incarceration. These results demonstrate that a great deal of trauma and PTSD goes unrecognized and untreated in this population, indicating the need for more effective treatment interventions. PMID- 26280106 TI - Fluorescent Properties of 8-Substituted BODIPY Dyes: Influence of Solvent Effects. AB - Three boron-dipyrrine (BODIPY) based dyes with bulky substituents in 8-position of dipyrrin ligand have been synthesized and characterized. Photophysical properties of the obtained compounds have been investigated in different individual solvents and solvent mixtures. Investigated compounds was found to be intensive fluorescent molecular rotors. The influence of different solvent parameters and the substituent nature on rotor characteristics have been observed and discussed. Minor changes in the nature of 8-substituent does not influence the spectral properties, but the presence of nitrogen donor atom in the phenyl substituent could be used for the sensing of the donor-acceptor interactions with solvent or dissolved compounds. The new approach of spectral properties correlation with solvent parameters was proposed, the viscosity parameter should be taken into account in case of BODIPYs with bulky substituents. The intensity of fluorescence molecular rotor properties decrease gradually with the viscosity increase above 1 cP. PMID- 26280107 TI - Identification of cardiac stem cells within mature cardiac myocytes. AB - Cardiac stem cells are described in a number of mammalian species including humans. Cardiac stem cell clusters consisting of both lineage-negative and partially committed cells are generally identified between contracting cardiac myocytes. In the present study, c-kit(+), Sca(+), and Isl1(+) stem cells were revealed to be located inside the sarcoplasm of cardiac myocytes in myocardial cell cultures derived from newborn, 20-, and 40-day-old rats. Intracellularly localized cardiac stem cells had a coating or capsule with a few pores that opened into the host cell sarcoplasm. The similar structures were also identified in the suspension of freshly isolated myocardial cells (ex vivo) of 20- and 40 day-old rats. The results from this study provide direct evidence for the replicative division of encapsulated stem cells, followed by their partial cardiomyogenic differentiation. The latter is substantiated by the release of multiple transient amplifying cells following the capsule rupture. In conclusion, functional cardiac stem cells can reside not only exterior to but also within cardiomyocytes. PMID- 26280102 TI - Comparison of Visual and Quantitative Florbetapir F 18 Positron Emission Tomography Analysis in Predicting Mild Cognitive Impairment Outcomes. AB - IMPORTANCE: The applicability of beta-amyloid peptide (Abeta) positron emission tomography (PET) as a biomarker in clinical settings to aid in selection of individuals at preclinical and prodromal Alzheimer disease (AD) will depend on the practicality of PET image analysis. In this context, visual-based Abeta PET assessment seems to be the most feasible approach. OBJECTIVES: To determine the agreement between visual and quantitative Abeta PET analysis and to assess the ability of both techniques to predict conversion from mild cognitive impairment (MCI) to AD. DESIGN, SETTING, AND PARTICIPANTS: A longitudinal study was conducted among the Alzheimer's Disease Neuroimaging Initiative (ADNI) sites in the United States and Canada during a 1.6-year mean follow-up period. The study was performed from September 21, 2010, to August 11, 2014; data analysis was conducted from September 21, 2014, to May 26, 2015. Participants included 401 individuals with MCI receiving care at a specialty clinic (219 [54.6%] men; mean [SD] age, 71.6 [7.5] years; 16.2 [2.7] years of education). All participants were studied with florbetapir F 18 [18F] PET. The standardized uptake value ratio (SUVR) positivity threshold was 1.11, and one reader rated all images, with a subset of 125 scans rated by a second reader. MAIN OUTCOMES AND MEASURES: Sensitivity and specificity of positive and negative [18F] florbetapir PET categorization, which was estimated with cerebrospinal fluid Abeta1-42 as the reference standard. Risk for conversion to AD was assessed using Cox proportional hazards regression models. RESULTS: The frequency of Abeta positivity was 48.9% (196 patients; visual analysis), 55.1% (221 patients; SUVR), and 64.8% (166 patients; cerebrospinal fluid), yielding substantial agreement between visual and SUVR data (kappa = 0.74) and between all methods (Fleiss kappa = 0.71). For approximately 10% of the 401 participants in whom visual and SUVR data disagreed, interrater reliability was moderate (kappa = 0.44), but it was very high if visual and quantitative results agreed (kappa = 0.92). Visual analysis had a lower sensitivity (79% vs 85%) but higher specificity (96% vs 90%), respectively, compared with SUVR. The conversion rate was 15.2% within a mean of 1.6 years, and a positive [18F] florbetapir baseline scan was associated with a 6.91-fold (SUVR) or 11.38-fold (visual) greater hazard for AD conversion, which changed only modestly after covariate adjustment for apolipoprotein epsilon4, concurrent fludeoxyglucose F 18 PET scan, and baseline cognitive status. CONCLUSIONS AND RELEVANCE: Visual and SUVR Abeta PET analysis may be equivalently used to determine Abeta status for individuals with MCI participating in clinical trials, and both approaches add significant value for clinical course prognostication. PMID- 26280108 TI - Cross-Contamination of Residual Emerging Contaminants and Antibiotic Resistant Bacteria in Lettuce Crops and Soil Irrigated with Wastewater Treated by Sunlight/H2O2. AB - The sunlight/H2O2 process has recently been considered as a sustainable alternative option compared to other solar driven advanced oxidation processes (AOPs) in advanced treatment of municipal wastewater (WW) to be reused for crop irrigation. Accordingly, in this study sunlight/H2O2 was used as disinfection/oxidation treatment for urban WW treatment plant effluent in a compound parabolic collector photoreactor to assess subsequent cross contamination of lettuce and soil by contaminants of emerging concern (CECs) (determined by QuEChERS extraction and LC-QqLIT-MS/MS analysis) and antibiotic resistant (AR) bacteria after irrigation with treated WW. Three CECs (carbamazepine (CBZ), flumequine (FLU), and thiabendazole (TBZ) at 100 MUg L(-1)) and two AR bacterial strains (E. coli and E. faecalis, at 10(5) CFU mL(-1)) were spiked in real WW. A detection limit (DL) of 2 CFU mL(-1) was reached after 120 min of solar exposure for AR E. coli, while AR E. faecalis was more resistant to the disinfection process (240 min to reach DL). CBZ and TBZ were poorly removed after 90 min (12% and 50%, respectively) compared to FLU (94%). Lettuce was irrigated with treated WW for 5 weeks. CBZ and TBZ were accumulated in soil up to 472 ng g(-1) and 256 ng g(-1) and up-taken by lettuce up to 109 and 18 ng g(-1), respectively, when 90 min treated WW was used for irrigation; whereas no bacteria contamination was observed when the bacterial density in treated WW was below the DL. A proper treatment time (>90 min) should be guaranteed in order to avoid the transfer of pathogens from disinfected WW to irrigated crops and soil. PMID- 26280109 TI - Quantitative Targeted Proteomics of Pancreatic Cancer: Deoxycytidine Kinase Protein Level Correlates to Progression-Free Survival of Patients Receiving Gemcitabine Treatment. AB - The purpose of the present study is to identify the determinant(s) of gemcitabine (dFdC)-sensitivity in pancreatic cancer tissues of patients treated with dFdC alone and in pancreatic cancer cell lines exposed to dFdC in vitro. Protein expression levels of 12 enzymes and 13 transporters potentially involved in transport and metabolism of dFdC in pancreatic cancer cell lines and tissues were quantified by means of our LC-MS/MS-based quantitative targeted proteomics technology. Protein expression levels of deoxycytidine kinase (dCK), uridine monophosphate-cytidine monophosphate (UMP-CMP) kinase, cytosolic nucleotidase III (cN-III), and equilibrative nucleoside transporter 1 (ENT1) were significantly correlated with IC50 or 1/IC50 in five cell lines with different sensitivities to dFdC (p < 0.05). Expression levels of the selected proteins in pancreatic cancer tissues of 10 patients with different progression-free survival (PFS) (49-955 days) were quantified, and their relationship with PFS was examined. Only the protein expression level of dCK was significantly correlated with PFS (p < 0.05). Multiple regression analysis was also performed, and combinations of ENT1, UMP CMP kinase, CTPS1, and dCK were highly correlated with PFS. Our results indicate that the protein expression level of dCK in pancreatic cancer tissue is a good predictor of PFS, and thus dCK may be the best biomarker of dFdC sensitivity in pancreatic cancer patients treated with dFdC, although other proteins would also contribute to dFdC-sensitivity at the cellular level in vivo and in vitro. PMID- 26280111 TI - Severe developmental delay and complete agenesis of corpus callosum in a Noonan syndrome patient with SOS1 mutation. PMID- 26280110 TI - Effects of Statin Treatment on Inflammation and Cardiac Function in Heart Failure: An Adjusted Indirect Comparison Meta-Analysis of Randomized Trials. AB - INTRODUCTION: Statins are known to prevent heart failure (HF). However, it is unclear whether statins as class or type (lipophilic or hydrophilic) improve outcomes of established HF. AIMS: The current meta-analysis was performed to compare the treatment effects of lipophilic and hydrophilic statins on inflammation and cardiac function in HF. Outcomes were indicators of cardiac function [changes in left ventricular ejection fraction (LVEF) and B-type natriuretic peptide (BNP)] and inflammation [changes in highly sensitive C reactive protein (hsCRP) and interluekin-6 (IL-6)]. METHOD: We conducted a search of PubMed, EMBASE, and the Cochrane databases until December 31, 2014 for randomized control trials (RCTs) of statin versus placebo in patients with HF. RCTs with their respective extracted information were dichotomized into statin type evaluated and analyzed separately. Outcomes were pooled with random effect approach, producing standardized mean differences (SMD) for each statin type. Using these pooled estimates, we performed adjusted indirect comparisons for each outcome. RESULTS: Data from 6214 patients from 19 trials were analyzed. Lipophilic statin was superior to hydrophilic statin treatment regarding follow up LVEF (SMD, 4.54; 95% CI, 4.16-4.91; P < 0.001), BNP (SMD, -1.60; 95% CI, -2.56 to -0.65; P < 0.001), hsCRP (SMD, -1.13; 95% CI, -1.54 to -0.72; P < 0.001), and IL-6 (SMD, -3.75; 95% CI, -4.77 to -0.72; P < 0.001) in HF. CONCLUSIONS: Lipophilic statin produces greater treatment effects on cardiac function and inflammation compared with hydrophilic statin in patients with HF. Until data from adequately powered head-to-head trial of the statin types are available, our meta-analysis brings clinicians and researchers a step closer to the quest on which statin--lipophilic or hydrophilic--is associated with better outcomes in HF. PMID- 26280116 TI - Deep Brain Stimulation of Heschl Gyrus: Implantation Technique, Intraoperative Localization, and Effects of Stimulation. AB - BACKGROUND: Tinnitus is a source of considerable morbidity, and neuromodulation has been shown to be a potential treatment option. However, the location of the primary auditory cortex within Heschl gyrus in the temporal operculum presents challenges for targeting and electrode implantation. OBJECTIVE: To determine whether anatomic targeting with intraoperative verification using evoked potentials can be used to implant electrodes directly into the Heschl gyrus (HG). METHODS: Nine patients undergoing stereo-electroencephalogram evaluation for epilepsy were enrolled. HG was directly targeted on volumetric magnetic resonance imaging, and framed stereotaxy was used to implant an electrode parallel to the axis of the gyrus by using an oblique anterolateral-posteromedial trajectory. Intraoperative evoked potentials from auditory stimuli were recorded from multiple electrode contacts. Postoperatively, stimulation of each electrode was performed and participants were asked to describe the percept. Audiometric analysis was performed for 2 participants during subthreshold stimulation. RESULTS: Sounds presented to the contralateral and ipsilateral ears produced evoked potentials in HG electrodes in all participants intraoperatively. Stimulation produced a reproducible sensation of sound in all participants with perceived volume proportional to amplitude. Four participants reported distinct sounds when different electrodes were stimulated, with more medial contacts producing tones perceived as higher in pitch. Stimulation was not associated with adverse audiometric effects. There were no complications of electrode implantation. CONCLUSION: Direct anatomic targeting with physiological verification can be used to implant electrodes directly into primary auditory cortex. If deep brain stimulation proves effective for intractable tinnitus, this technique may be useful to assist with electrode implantation. ABBREVIATIONS: DBS, deep brain stimulatorEEG, electroencephalographyHG, Heschl gyrus. PMID- 26280118 TI - CUR-65 Score for Community-Acquired Pneumonia Predicted Mortality Better Than CURB-65 Score in Low-Mortality Rate Settings. AB - BACKGROUND: It is not clear whether low-blood pressure criterion could be removed from CURB-65 (confusion, urea >7 mmol/L, respiratory rate >=30/min, low blood pressure and age >=65 years) score to orchestrate an improvement in identifying patients with community-acquired pneumonia (CAP) in low-mortality rate settings. METHODS: A retrospective cohort study of 1,230 CAP patients was performed to simplify the CURB-65 scoring system by excluding low-blood pressure variable. The simplification was validated in a prospective 2-center cohort of 1,409 adults with CAP. RESULTS: The hospital mortalities were 1.3% and 3.8% in the retrospective and prospective cohorts, respectively. The mortality rates in the 2 cohorts increased directly with the increasing scores, showing significant increased odds ratios for mortality. The pattern of sensitivity, specificity, positive predictive value and Youden's index of a CUR-65 (Confusion, Urea >7 mmol/L, Respiratory rate >=30/min and age >=65 years) score of >=2 for prediction of mortality was better than that of a CURB-65 score of >=3 in the retrospective cohort. Higher values of corresponding indices were confirmed in the validation cohort. The higher accuracy of CUR-65 score for predicting mortality was illustrated by the area under the receiver operating characteristic curve of 0.937, compared with 0.915 for CURB-65 score in the retrospective cohort (P = 0.0073). The validation cohort confirmed a similar paradigm (0.953 versus 0.907, P = 0.0002). CONCLUSIONS: CURB-65 score could be simplified by removing low blood pressure to orchestrate an improvement in predicting mortality in CAP patients who have a low risk of death. A CUR-65 score of >=2 might be a more valuable cutoff value for severe CAP. PMID- 26280117 TI - Elevated Baseline C-Reactive Protein as a Predictor of Outcome After Aneurysmal Subarachnoid Hemorrhage: Data From the Simvastatin in Aneurysmal Subarachnoid Hemorrhage (STASH) Trial. AB - BACKGROUND: There remains a proportion of patients with unfavorable outcomes after aneurysmal subarachnoid hemorrhage, of particular relevance in those who present with a good clinical grade. A forewarning of those at risk provides an opportunity towards more intensive monitoring, investigation, and prophylactic treatment prior to the clinical manifestation of advancing cerebral injury. OBJECTIVE: To assess whether biochemical markers sampled in the first days after the initial hemorrhage can predict poor outcome. METHODS: All patients recruited to the multicenter Simvastatin in Aneurysmal Hemorrhage Trial (STASH) were included. Baseline biochemical profiles were taken between time of ictus and day 4 post ictus. The t-test compared outcomes, and a backwards stepwise binary logistic regression was used to determine the factors providing independent prediction of an unfavorable outcome. RESULTS: Baseline biochemical data were obtained in approximately 91% of cases from 803 patients. On admission, 73% of patients were good grade (World Federation of Neurological Surgeons grades 1 or 2); however, 84% had a Fisher grade 3 or 4 on computed tomographic scan. For patients presenting with good grade on admission, higher levels of C-reactive protein, glucose, and white blood cells and lower levels of hematocrit, albumin, and hemoglobin were associated with poor outcome at discharge. C-reactive protein was found to be an independent predictor of outcome for patients presenting in good grade. CONCLUSION: Early recording of C-reactive protein may prove useful in detecting those good grade patients who are at greater risk of clinical deterioration and poor outcome. PMID- 26280119 TI - Glucocorticoid-induced tumor necrosis factor receptor-related protein co stimulation facilitates tumor regression by inducing IL-9-producing helper T cells. AB - T cell stimulation via glucocorticoid-induced tumor necrosis factor receptor (TNFR)-related protein (GITR) elicits antitumor activity in various tumor models; however, the underlying mechanism of action remains unclear. Here we demonstrate a crucial role for interleukin (IL)-9 in antitumor immunity generated by the GITR agonistic antibody DTA-1. IL-4 receptor knockout (Il4ra(-/-)) mice, which have reduced expression of IL-9, were resistant to tumor growth inhibition by DTA-1. Notably, neutralization of IL-9 considerably impaired tumor rejection induced by DTA-1. In particular, DTA-1-induced IL-9 promoted tumor-specific cytotoxic T lymphocyte (CTL) responses by enhancing the function of dendritic cells in vivo. Furthermore, GITR signaling enhanced the differentiation of IL-9-producing CD4(+) T-helper (TH9) cells in a TNFR-associated factor 6 (TRAF6)- and NF-kappaB dependent manner and inhibited the generation of induced regulatory T cells in vitro. Our findings demonstrate that GITR co-stimulation mediates antitumor immunity by promoting TH9 cell differentiation and enhancing CTL responses and thus provide a mechanism of action for GITR agonist-mediated cancer immunotherapies. PMID- 26280120 TI - In vivo imaging and tracking of host-microbiota interactions via metabolic labeling of gut anaerobic bacteria. AB - The intestine is densely populated by anaerobic commensal bacteria. These microorganisms shape immune system development, but understanding of host commensal interactions is hampered by a lack of tools for studying the anaerobic intestinal environment. We applied metabolic oligosaccharide engineering and bioorthogonal click chemistry to label various commensal anaerobes, including Bacteroides fragilis, a common and immunologically important commensal. We studied the dissemination of B. fragilis after acute peritonitis and characterized the interactions of the intact microbe and its polysaccharide components in myeloid and B cell lineages. We were able to assess the distribution and colonization of labeled B. fragilis along the intestine, as well as niche competition after coadministration of multiple species of the microbiota. We also fluorescently labeled nine additional commensals (eight anaerobic and one microaerophilic) from three phyla common in the gut- Bacteroidetes, Firmicutes and Proteobacteria--as well as one aerobic pathogen (Staphylococcus aureus). This strategy permits visualization of the anaerobic microbial niche by various methods, including intravital two-photon microscopy and non-invasive whole-body imaging, and can be used to study microbial colonization and host-microbe interactions in real time. PMID- 26280123 TI - A brief psychological intervention to protect subjective well-being in a community sample. AB - PURPOSE: Governments are using measures of subjective well-being in preference to more objective measures of social progress (e.g., gross domestic product), yet interventions to address well-being are often costly. The present study tests the ability of a brief psychological intervention based on self-affirmation theory (Steele in Advances in experimental social psychology, Academic Press, New York, 1988) to protect subjective well-being among a community sample likely to have diminished well-being (i.e., women aged 46 years and older, Inglehart in Int J Comp Sociol 43: 391-408, 2002. doi: 10.1177/002071520204300309). METHODS: One hundred and forty women aged 46 years and older completed baseline measures of subjective well-being, interpersonal feelings and self-esteem at baseline before being randomized to a self-affirmation or control group. Subjective well-being, interpersonal feelings and self-esteem were assessed again at follow-up. RESULTS: Results showed that, controlling for baseline subjective well-being, the well being of women who had self-affirmed was significantly higher at follow-up than those in the control condition. Affirming the self did not significantly influence interpersonal feelings or self-esteem, compared with the control condition. CONCLUSIONS: The findings suggest that a low-cost brief psychological intervention based on self-affirmation theory, with potentially large public health "reach," could be used to protect subjective well-being-a key aim of government policies. PMID- 26280124 TI - The economic case for low carbon waste management in rapidly growing cities in the developing world: The case of Palembang, Indonesia. AB - The provision of appropriate waste management is not only an indicator of development but also of broader sustainability. This is particularly relevant to expanding cities in developing countries faced with rising waste generation and associated environmental health problems. Despite these urgent issues, city authorities often lack the evidence required to make well-informed decisions. This study evaluates the carbon and economic performance of low-carbon measures in the waste sector at a city level, within the context of a developing country. Palembang in Indonesia is used as a case of a medium-sized city in a newly industrialized country, with relevance to other similar cities in the developing world. Evidence suggests that the waste sector can achieve substantial carbon emission reductions, and become a carbon sink, in a cost effective way. Hence there is an economic case for a low carbon development path for Palembang, and possibly for other cities in developing and developed countries facing similar challenges. PMID- 26280121 TI - Tumor necrosis factor-alpha confers cardioprotection through ectopic expression of keratins K8 and K18. AB - Tumor necrosis factor-alpha (TNF-alpha), one of the major stress-induced proinflammatory cytokines, is upregulated in the heart after tissue injury, and its sustained expression can contribute to the development of heart failure. Whether TNF-alpha also exerts cytoprotective effects in heart failure is not known. Here we provide evidence for a cardioprotective function of TNF-alpha in a genetic heart failure model, desmin-deficient mice. The cardioprotective effects of TNF-alpha are a consequence of nuclear factor-kappaB (NF-kappaB)-mediated ectopic expression in cardiomyocytes of keratin 8 (K8) and keratin 18 (K18), two epithelial-specific intermediate filament proteins. In cardiomyocytes, K8 and K18 (K8/K18) formed an alternative cytoskeletal network that localized mainly at intercalated discs (IDs) and conferred cardioprotection by maintaining normal ID structure and mitochondrial integrity and function. Ectopic induction of K8/K18 expression in cardiomyocytes also occurred in other genetic and experimental models of heart failure. Loss of the K8/K18 network resulted in a maladaptive cardiac phenotype following transverse aortic constriction. In human failing myocardium, where TNF-alpha expression is upregulated, K8/K18 were also ectopically expressed and localized primarily at IDs, which did not contain detectable amounts of desmin. Thus, TNF-alpha- and NF-kappaB-mediated formation of an alternative, stress-induced intermediate filament cytoskeleton has cardioprotective function in mice and potentially in humans. PMID- 26280125 TI - A universal calibrated model for the evaluation of surface water and groundwater quality: Model development and a case study in China. AB - Water quality evaluation is an important issue in environmental management. Various methods have been used to evaluate the quality of surface water and groundwater. However, all previous studies have used different evaluation models for surface water and groundwater, and the models must be recalibrated due to changes in monitoring indicators in each evaluation. Water quality managers would benefit from a universal and effective model based on a simple expression that would be suitable for all cases of surface water and groundwater, and which could therefore serve as a standard method for a region or country. To meet this requirement, we attempted to develop a universal calibrated model based on the radial basis function neural network. In the new model, the units and values of the evaluation indicators for surface water and groundwater are normalized simultaneously to make the data directly comparable. The model's training inputs comprise the normalized value in each of a water quality indicator's grades (e.g., the nitrate contents defined in a regulatory standard for grades I to V) for all evaluation indicators. The central vector of the Gaussian function is used as the average of the evaluation indicators' normalized standard values for the five grades. The final calibrated model is expressed as an equation rather than in a programming language, and is therefore easier to use. We used the model in a Chinese case study, and found that the model was feasible (it compared well with the results of other models) and simple to use for the evaluation of surface water and groundwater quality. PMID- 26280122 TI - APP intracellular domain-WAVE1 pathway reduces amyloid-beta production. AB - An increase in amyloid-beta (Abeta) production is a major pathogenic mechanism associated with Alzheimer's disease (AD), but little is known about possible homeostatic control of the amyloidogenic pathway. Here we report that the amyloid precursor protein (APP) intracellular domain (AICD) downregulates Wiskott-Aldrich syndrome protein (WASP)-family verprolin homologous protein 1 (WAVE1 or WASF1) as part of a negative feedback mechanism to limit Abeta production. The AICD binds to the Wasf1 promoter, negatively regulates its transcription and downregulates Wasf1 mRNA and protein expression in Neuro 2a (N2a) cells. WAVE1 interacts and colocalizes with APP in the Golgi apparatus. Experimentally reducing WAVE1 in N2a cells decreased the budding of APP-containing vesicles and reduced cell-surface APP, thereby reducing the production of Abeta. WAVE1 downregulation was observed in mouse models of AD. Reduction of Wasf1 gene expression dramatically reduced Abeta levels and restored memory deficits in a mouse model of AD. A decrease in amounts of WASF1 mRNA was also observed in human AD brains, suggesting clinical relevance of the negative feedback circuit involved in homeostatic regulation of Abeta production. PMID- 26280126 TI - CT of gastro-duodenal obstruction. AB - Gastro-duodenal obstruction encompasses a spectrum of benign and malignant disease. Historically, chronic peptic ulcer disease was the main cause of gastro duodenal obstruction, whereas now malignant cause with gastric carcinomas for gastric obstruction and pancreatic tumors for duodenal obstruction predominate. This paper reviews the role of CT in diagnosing gastro-duodenal obstruction, its level, its cause by identifying intraluminal, parietal, or extrinsic process, and the presence of complication. PMID- 26280127 TI - Pancreatic neuroendocrine tumors: correlation between histogram analysis of apparent diffusion coefficient maps and tumor grade. AB - PURPOSE: To explore the role of histogram analysis of apparent diffusion coefficient (ADC) MRI maps based on entire tumor volume data in determining pancreatic neuroendocrine tumor (PNT) grade. METHODS AND MATERIALS: Retrospective evaluation of 22 patients with PNTs included low-grade (G1; n = 15), intermediate grade (G2; n = 4), and high-grade (G3; n = 3) tumors. Regions of interest containing the lesion were drawn on every section of the ADC map containing the tumor and summated to obtain histograms for entire tumor volume. Calculated histographic parameters included mean ADC (mADC), 5th percentile ADC, 10th percentile ADC, 25th percentile ADC, 50th percentile ADC, 75th percentile ADC (ADC75), 90th percentile ADC (ADC90) and 95th percentile ADC (ADC95), skewness and kurtosis. Histogram parameters were correlated with tumor grade by repeated measures analysis of variance with Tukey-Kramer post hoc comparisons. RESULTS: The mADC, ADC75, ADC90, and ADC95 were significantly higher in G1 tumors (1283 +/ 267; 1404 +/- 300; 1495 +/- 318; 1562 +/- 347 * 10(-6) mm(2)/s) compared to G2 (892 +/- 390; 952 +/- 381; 1036 +/- 384; 1072 +/- 374 * 10(-6) mm(2)/s) and to G3 tumors (733 +/- 225; 864 +/- 284; 1008 +/- 288; 1152 +/- 192 * 10(-6) mm(2)/s) (p value <0.05). Skewness and kurtosis were significantly different between G1 (0.041 +/- 0.466; 2.802 +/- 0.679) and G3 (1.01 +/- 1.140; 5.963 +/- 4.008) tumors (p value <0.05). Tumor volume (mL) was significantly higher on G3 (55 +/- 15.7) compared to G1 (1.9 +/- 2.7) and G2 (4.5 +/- 3.6) tumors (p value <0.05). In this small sample size, we did not detect statistically significant parameters between G2 (n = 4) and G3 (n = 3) tumors. CONCLUSIONS: Histographic analysis of ADC maps on the basis of the entire tumor volume can be useful in differentiating histologic grades of PNTs. PMID- 26280128 TI - Diets Containing alpha-Linolenic (omega3) or Oleic (omega9) Fatty Acids Rescues Obese Mice From Insulin Resistance. AB - Subclinical systemic inflammation is a hallmark of obesity and insulin resistance. The results obtained from a number of experimental studies suggest that targeting different components of the inflammatory machinery may result in the improvement of the metabolic phenotype. Unsaturated fatty acids exert antiinflammatory activity through several distinct mechanisms. Here, we tested the capacity of omega3 and omega9 fatty acids, directly from their food matrix, to exert antiinflammatory activity through the G protein-coupled receptor (GPR)120 and GPR40 pathways. GPR120 was activated in liver, skeletal muscle, and adipose tissues, reverting inflammation and insulin resistance in obese mice. Part of this action was also mediated by GPR40 on muscle, as a novel mechanism described. Pair-feeding and immunoneutralization experiments reinforced the pivotal role of GPR120 as a mediator in the response to the nutrients. The improvement in insulin sensitivity in the high-fat substituted diets was associated with a marked reduction in tissue inflammation, decreased macrophage infiltration, and increased IL-10 levels. Furthermore, improved glucose homeostasis was accompanied by the reduced expression of hepatic gluconeogenic enzymes and reduced body mass. Thus, our data indicate that GPR120 and GPR40 play a critical role as mediators of the beneficial effects of dietary unsaturated fatty acids in the context of obesity-induced insulin resistance. PMID- 26280129 TI - Bile Acids Trigger GLP-1 Release Predominantly by Accessing Basolaterally Located G Protein-Coupled Bile Acid Receptors. AB - Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein-coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear farnesoid receptor and the apical sodium-coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release and to determine whether bile acids target their receptors on GLP-1 secreting L-cells from the apical or basolateral compartment. Using transgenic mice expressing fluorescent sensors specifically in L-cells, we observed that taurodeoxycholate (TDCA) and taurolithocholate (TLCA) increased intracellular cAMP and Ca(2+). In primary intestinal cultures, TDCA was a more potent GLP-1 secretagogue than taurocholate (TCA) and TLCA, correlating with a stronger Ca(2+) response to TDCA. Using small-volume Ussing chambers optimized for measuring GLP 1 secretion, we found that both a GPBAR1 agonist and TDCA stimulated GLP-1 release better when applied from the basolateral than from the luminal direction and that luminal TDCA was ineffective when intestinal tissue was pretreated with an ASBT inhibitor. ASBT inhibition had no significant effect in nonpolarized primary cultures. Studies in the perfused rat gut confirmed that vascularly administered TDCA was more effective than luminal TDCA. Intestinal primary cultures and Ussing chamber-mounted tissues from GPBAR1-knockout mice did not secrete GLP-1 in response to either TLCA or TDCA. We conclude that the action of bile acids on GLP-1 secretion is predominantly mediated by GPBAR1 located on the basolateral L-cell membrane, suggesting that stimulation of gut hormone secretion may include postabsorptive mechanisms. PMID- 26280130 TI - Protective Hematopoietic Effect of Estrogens in a Mouse Model of Thrombosis: Respective Roles of Nuclear Versus Membrane Estrogen Receptor alpha. AB - We recently reported that chronic 17beta-estradiol (E2) treatment in mice decreases platelet responsiveness, prolongs the tail-bleeding time and protects against acute thromboembolism via the hematopoietic estrogen receptor alpha (ERalpha), and independently of ERbeta. Here, we have explored the respective roles of membrane vs nuclear actions of ERalpha in this process, using: 1) the selective activator of membrane ERalpha: estrogen dendrimer conjugate, and 2) mouse models with mutations in ERalpha. The selective targeting of activation function 2 of ERalpha provides a model of nuclear ERalpha loss-of-function, whereas mutation of the ERalpha palmitoylation site leads to a model of membrane ERalpha deficiency. The combination of pharmacological and genetic approaches including hematopoietic chimera mice demonstrated that absence of either membrane or nuclear ERalpha activation in bone marrow does not prevent the prolongation of the tail-bleeding time, suggesting a redundancy of these two functions for this E2 effect. In addition, although hematopoietic membrane ERalpha is neither sufficient nor necessary to protect E2-treated mice from collagen/epinephrine induced thromboembolism, the protection against death-induced thromboembolism is significantly reduced in the absence of hematopoietic nuclear ERalpha activation. Overall, this study emphasizes that hematopoietic cells (likely megakaryocytes and possibly immune cells) constitute an important target in the antithrombotic effects of estrogens, and delineate for the first time in vivo the respective roles of membrane vs nuclear ERalpha effects, with a prominent role of the latter. PMID- 26280131 TI - Bioinspired Nonheme Iron Catalysts for C-H and C?C Bond Oxidation: Insights into the Nature of the Metal-Based Oxidants. AB - Recent efforts to design synthetic iron catalysts for the selective and efficient oxidation of C-H and C?C bonds have been inspired by a versatile family of nonheme iron oxygenases. These bioinspired nonheme (N4)Fe(II) catalysts use H2O2 to oxidize substrates with high regio- and stereoselectivity, unlike in Fenton chemistry where highly reactive but unselective hydroxyl radicals are produced. In this Account, we highlight our efforts to shed light on the nature of metastable peroxo intermediates, which we have trapped at -40 degrees C, in the reactions of the iron catalyst with H2O2 under various conditions and the high valent species derived therefrom. Under the reaction conditions that originally led to the discovery of this family of catalysts, we have characterized spectroscopically an Fe(III)-OOH intermediate (EPR g(max) = 2.19) that leads to the hydroxylation of substrate C-H bonds or the epoxidation and cis dihydroxylation of C?C bonds. Surprisingly, these organic products show incorporation of (18)O from H2(18)O, thereby excluding the possibility of a direct attack of the Fe(III)-OOH intermediate on the substrate. Instead, a water assisted mechanism is implicated in which water binding to the iron(III) center at a site adjacent to the hydroperoxo ligand promotes heterolytic cleavage of the O-O bond to generate an Fe(V)(O)(OH) oxidant. This mechanism is supported by recent kinetic studies showing that the Fe(III)-OOH intermediate undergoes exponential decay at a rate enhanced by the addition of water and retarded by replacement of H2O with D2O, as well as mass spectral evidence for the Fe(V)(O)(OH) species obtained by the Costas group. The nature of the peroxo intermediate changes significantly when the reactions are carried out in the presence of carboxylic acids. Under these conditions, spectroscopic studies support the formation of a (kappa(2)-acylperoxo)iron(III) species (EPR g(max) = 2.58) that decays at -40 degrees C in the absence of substrate to form an oxoiron(IV) byproduct, along with a carboxyl radical that readily loses CO2. The alkyl radical thus formed either reacts with O2 to form benzaldehyde (as in the case of PhCH2COOH) or rebounds with the incipient Fe(IV)(O) moiety to form phenol (as in the case of C6F5COOH). Substrate addition leads to its 2-e(-) oxidation and inhibits these side reactions. The emerging mechanistic picture, supported by DFT calculations of Wang and Shaik, describes a rather flat reaction landscape in which the (kappa(2)-acylperoxo)iron(III) intermediate undergoes O-O bond homolysis reversibly to form an Fe(IV)(O)((*)OC(O)R) species that decays to Fe(IV)(O) and RCO2(*) or isomerizes to its Fe(V)(O)(O2CR) electromer, which effects substrate oxidation. Another short-lived S = 1/2 species just discovered by Talsi that has much less g-anisotropy (EPR g(max) = 2.07) may represent either of these postulated high-valent intermediates. PMID- 26280133 TI - Plastic responses in the metabolome and functional traits of maize plants to temperature variations. AB - Environmentally inducible phenotypic plasticity is a major player in plant responses to climate change. However, metabolic responses and their role in determining the phenotypic plasticity of plants that are subjected to temperature variations remain poorly understood. The metabolomic profiles and metabolite levels in the leaves of three maize inbred lines grown in different temperature conditions were examined with a nuclear magnetic resonance metabolomic technique. The relationship of functional traits to metabolome profiles and the metabolic mechanism underlying temperature variations were then explored. A comparative analysis showed that during heat and cold stress, maize plants shared common plastic responses in biomass accumulation, carbon, nitrogen, sugars, some amino acids and compatible solutes. We also found that the plastic response of maize plants to heat stress was different from that under cold stress, mainly involving biomass allocation, shikimate and its aromatic amino acid derivatives, and other non-polar metabolites. The plastic responsiveness of functional traits of maize lines to temperature variations was low, while the metabolic responsiveness in plasticity was high, indicating that functional and metabolic plasticity may play different roles in maize plant adaptation to temperature variations. A linear regression analysis revealed that the maize lines could adapt to growth temperature variations through the interrelation of plastic responses in the metabolomes and functional traits, such as biomass allocation and the status of carbon and nitrogen. We provide valuable insight into the plastic response strategy of maize plants to temperature variations that will permit the optimisation of crop cultivation in an increasingly variable environment. PMID- 26280132 TI - Health, work and working conditions: a review of the European economic literature. AB - Economists have traditionally been very cautious when studying the interaction between employment and health because of the two-way causal relationship between these two variables: health status influences the probability of being employed and, at the same time, working affects the health status. Because these two variables are determined simultaneously, researchers control endogeneity skews (e.g., reverse causality, omitted variables) when conducting empirical analysis. With these caveats in mind, the literature finds that a favourable work environment and high job security lead to better health conditions. Being employed with appropriate working conditions plays a protective role on physical health and psychiatric disorders. By contrast, non-employment and retirement are generally worse for mental health than employment, and overemployment has a negative effect on health. These findings stress the importance of employment and of adequate working conditions for the health of workers. In this context, it is a concern that a significant proportion of European workers (29 %) would like to work fewer hours because unwanted long hours are likely to signal a poor level of job satisfaction and inadequate working conditions, with detrimental effects on health. Thus, in Europe, labour-market policy has increasingly paid attention to job sustainability and job satisfaction. The literature clearly invites employers to take better account of the worker preferences when setting the number of hours worked. Overall, a specific "flexicurity" (combination of high employment protection, job satisfaction and active labour-market policies) is likely to have a positive effect on health. PMID- 26280134 TI - Autistic Traits Moderate the Impact of Reward Learning on Social Behaviour. AB - A deficit in empathy has been suggested to underlie social behavioural atypicalities in autism. A parallel theoretical account proposes that reduced social motivation (i.e., low responsivity to social rewards) can account for the said atypicalities. Recent evidence suggests that autistic traits modulate the link between reward and proxy metrics related to empathy. Using an evaluative conditioning paradigm to associate high and low rewards with faces, a previous study has shown that individuals high in autistic traits show reduced spontaneous facial mimicry of faces associated with high vs. low reward. This observation raises the possibility that autistic traits modulate the magnitude of evaluative conditioning. To test this, we investigated (a) if autistic traits could modulate the ability to implicitly associate a reward value to a social stimulus (reward learning/conditioning, using the Implicit Association Task, IAT); (b) if the learned association could modulate participants' prosocial behaviour (i.e., social reciprocity, measured using the cyberball task); (c) if the strength of this modulation was influenced by autistic traits. In 43 neurotypical participants, we found that autistic traits moderated the relationship of social reward learning on prosocial behaviour but not reward learning itself. This evidence suggests that while autistic traits do not directly influence social reward learning, they modulate the relationship of social rewards with prosocial behaviour. PMID- 26280136 TI - Fluoride: The Family Physician's Role. PMID- 26280137 TI - Primary Care Physicians Are More Likely to Participate in Medicare EHR Incentives than Other Eligible Physicians. PMID- 26280139 TI - Rosacea: Diagnosis and Treatment. AB - Rosacea is a chronic facial skin condition of unknown cause. It is characterized by marked involvement of the central face with transient or persistent erythema, telangiectasia, inflammatory papules and pustules, or hyperplasia of the connective tissue. Transient erythema, or flushing, is often accompanied by a feeling of warmth. It usually lasts for less than five minutes and may spread to the neck and chest. Less common findings include erythematous plaques, scaling, edema, phymatous changes (thickening of skin due to hyperplasia of sebaceous glands), and ocular symptoms. The National Rosacea Society Expert Committee defines four subtypes of rosacea (erythematotelangiectatic, papulopustular, phymatous, and ocular) and one variant (granulomatous). Treatment starts with avoidance of triggers and use of mild cleansing agents and moisturizing regimens, as well as photoprotection with wide-brimmed hats and broad-spectrum sunscreens (minimum sun protection factor of 30). For inflammatory lesions and erythema, the recommended initial treatments are topical metronidazole or azelaic acid. Once daily brimonidine, a topical alpha-adrenergic receptor agonist, is effective in reducing erythema. Papulopustular rosacea can be treated with systemic therapy including tetracyclines, most commonly subantimicrobial-dose doxycycline. Phymatous rosacea is treated primarily with laser or light-based therapies. Ocular rosacea is managed with lid hygiene, topical cyclosporine, and topical or systemic antibiotics. PMID- 26280140 TI - Management of Spontaneous Vaginal Delivery. AB - Most of the nearly 4 million births in the United States annually are normal spontaneous vaginal deliveries. In the first stage of labor, normal birth outcomes can be improved by encouraging the patient to walk and stay in upright positions, waiting until at least 6 cm dilation to diagnose active stage arrest, providing continuous labor support, using intermittent auscultation in low-risk deliveries, and following the Centers for Disease Control and Prevention guidelines for group B streptococcus prophylaxis. Most women with a low transverse uterine incision are candidates for a trial of labor after cesarean delivery and should be counseled accordingly. Pain management during labor includes complementary modalities and systemic opioids, epidural anesthesia, and pudendal block. Outcomes in the second stage of labor can be improved by using warm perineal compresses, allowing women more time to push before intervening, and offering labor support. Delayed pushing increases the length of the second stage of labor and does not affect the rate of spontaneous vaginal delivery. A tight nuchal cord can be clamped twice and cut before delivery of the shoulders, or the baby may be delivered using a somersault maneuver in which the cord is left nuchal and the distance from the cord to placenta minimized by pushing the head toward the maternal thigh. After delivery, skin-to-skin contact with the mother is recommended. Beyond 35 weeks' gestation, there is no benefit to bulb suctioning the nose and mouth. Postpartum maternal and neonatal outcomes can be improved through delayed cord clamping, active management to prevent postpartum hemorrhage, careful examination for external anal sphincter injuries, and use of absorbable synthetic suture for second-degree perineal laceration repair. Practices that will not improve outcomes and may result in negative outcomes include discontinuation of epidurals late in labor and routine episiotomy. PMID- 26280141 TI - Common Skin Rashes in Children. AB - Because childhood rashes may be difficult to differentiate by appearance alone, it is important to consider the entire clinical presentation to help make the appropriate diagnosis. Considerations include the appearance and location of the rash; the clinical course; and associated symptoms, such as pruritus or fever. A fever is likely to occur with roseola, erythema infectiosum (fifth disease), and scarlet fever. Pruritus sometimes occurs with atopic dermatitis, pityriasis rosea, erythema infectiosum, molluscum contagiosum, and tinea infection. The key feature of roseola is a rash presenting after resolution of a high fever, whereas the distinguishing features in pityriasis rosea are a herald patch and a bilateral and symmetric rash in a Christmas tree pattern. The rash associated with scarlet fever usually develops on the upper trunk, then spreads throughout the body, sparing the palms and soles. Impetigo is a superficial bacterial infection that most commonly affects the face and extremities of children. Erythema infectiosum is characterized by a viral prodrome followed by the "slapped cheek" facial rash. Flesh-colored or pearly white papules with central umbilication occur with molluscum contagiosum, a highly contagious viral infection that usually resolves without intervention. Tinea is a common fungal skin infection in children that affects the scalp, body, groin, feet, hands, or nails. Atopic dermatitis is a chronic, relapsing inflammatory skin condition that may present with a variety of skin changes. PMID- 26280142 TI - Beyond Meaningful Use: Reconciling Medications. PMID- 26280143 TI - Hyperpigmented Plaques on the Feet. PMID- 26280149 TI - Tap Water vs. Sterile Saline for Wound Irrigation. PMID- 26280150 TI - Rosacea. PMID- 26280151 TI - Perceived Stress and Elder Abuse: A Population-Based Study of Adult Protective Services Cases in Chicago. AB - OBJECTIVES: To characterize the relationship between perceived stress and Adult Protective Services (APS) elder abuse cases in a population-based sample. DESIGN: Cross-sectional. SETTING: Chicago. PARTICIPANTS: community-dwelling, older adults (N = 8,558; mean age 74 +/- 7, 62% female, 64% African American). MEASUREMENTS: Perceived Stress Scale (PSS), APS database linkage. RESULTS: Bivariate and adjusted analyses showed that perceived stress was significantly higher in APS clients than in participants without any APS interaction for various subtypes of abuse (e.g., abuse from a perpetrator and self-neglect). This relationship was strongest for those with a confirmed history of abuse from a perpetrator, with a medium-large effect size (t = -5.8, P < .001, Cohen D = -0.6). Those in the highest stress tertile had a likelihood of having confirmed history of abuse from a perpetrator that was nearly three times as great as that of those in lower stress tertiles (odds ratio = 2.7, 95% confidence interval = 1.2-6.2). Analyses of individual PSS items revealed a robust relationship between distress items and APS involvement. Items reflecting coping were inconsistently associated with elder abuse. CONCLUSION: Clients of APS have higher levels of perceived stress, and abuse from a perpetrator strengthens this relationship. Therefore, victims of abuse from a perpetrator may be at the highest risk of stress-related consequences and should be targeted for intervention efforts that enhance empowerment and effective coping strategies. PMID- 26280152 TI - Accelerated Submonomer Solid-Phase Synthesis of Peptoids Incorporating Multiple Substituted N-Aryl Glycine Monomers. AB - N-Aryl glycines are a chemically diverse class of peptoid monomers that have strong structure-inducing propensities. Yet their use has been limited due to the sluggish reactivity of the weakly nucleophilic aniline submonomers. Here, we report up to a 76-fold rate acceleration of the displacement reaction using aniline submonomers in solid-phase peptoid synthesis. This is achieved by adding halophilic silver salts to the displacement reaction, facilitating bromide abstraction and AgBr precipitation. Mechanistic insight derived from analysis of a series of 15 substituted anilines reveals that the silver-mediated reaction proceeds through a transition state that has considerably less positive charge buildup on the incoming nucleophile and an enhanced leaving group. This straightforward enhancement to the submonomer method enables the rapid room temperature synthesis of a wide variety of N-aryl glycine-rich peptoid oligomers, possessing both electron-withdrawing and -donating substituents, in good yields. PMID- 26280154 TI - Polymorphisms at IL28B gene as predictors of viral relapse in genotype 4 Egyptian hepatitis C patients. AB - Chronic HCV is one of the commonest causes of chronic liver disease worldwide with about 15% of population infected in Egypt. Certain single nucleotide polymorphisms (SNPs) lying near the IL28B gene were found to affect the spontaneous clearance as well as treatment outcome of HCV. To examine the association between different IL28B variants and the relapse of HCV infection after combined therapy with ribavirin and pegylated interferon (pegIFN). Hundered HCV genotype four patients received 1.5 mg/kg/week peginterferon alfa-2b plus 800 1400 mg/d ribavirin (weight-adjusted) for 48 weeks. IL28B polymorphisms (rs12980275, rs12979860, and 1 rs8099917) were studied in responders and relapsers at week 72. Out of 69 patients receiving treatment, 13 (18.8%) were relapsers. By stratifying patients on the basis of the IL-28/60 genotype (CC vs. CT/TT), CC patients showed lower relapse rates (2.3%) compared with CT/TT patients (46.2%) (P < 0.001). On the basis of the IL-28/75 genotype (GG vs. GA/AA), the GG patients achieved higher relapse rates (62.5%) compared with GA/AA patients (13.1%) (P = 0.004). Moreover, no statistical significant difference was observed between the TT patients compared with GG/GT patients on the basis of the IL-28/17 genotype. SNPs at IL-28/60 and IL-28/75 are possible predictors of relapse in patients receiving dual treatment. PMID- 26280153 TI - Dementia with Lewy bodies can be well-differentiated from Alzheimer's disease by measurement of brain acetylcholinesterase activity-a [11C]MP4A PET study. AB - OBJECTIVE: To investigate the diagnostic performance of brain acetylcholinesterase (AChE) activity measurement using N-[(11) C]-methyl-4 piperidyl acetate (MP4A) and PET in patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). METHODS: Participants were 14 DLB patients, 25 AD patients and 18 age-matched healthy controls (HC). All subjects underwent PET scans and MP4A to measure regional brain AChE activity. We performed anatomical standardization of each brain image, and k3 values, an index of AChE activity, in each voxel were estimated by nonlinear least squares analysis. Volumes of interest (VOIs) were identified on parametric k3 images in frontal, temporal, parietal and occipital cortices, and in anterior and posterior cingulate gyri (ACG and PCG). In each VOI, the differential diagnostic performance between AD and DLB of k3 values was assessed by area under the curve (AUC) of the receiver operating characteristic. Voxel-based statistical analyses were also performed. RESULTS: Mean cortical AChE activities in AD patients (-8.2% compared with normal mean) and DLB patients (-27.8%) were lower than HCs (p < 0.05, p < 0.001, respectively). There was a significant difference in mean cortical AChE activities between AD and DLB patients (p < 0.001). All regional brain AChE activities of defined VOIs except ACG were able to well discriminate DLB from AD, and notably performance was the most significant in PCG (AUC = 0.989, 95% CI: 0.965-1.000). CONCLUSIONS: Brain cholinergic deficit is consistently prominent in DLB compared with AD. PET measurement of brain AChE activity may be useful for the differential diagnosis between DLB and AD. PMID- 26280155 TI - Reply to it is not all black and white: Future incidence of stomach cancer will be substantially higher than projected due to the effects of immigration and increasing Hispanic and Asian populations in the United States. PMID- 26280156 TI - Continuous vs. tapering application of the potent topical corticosteroid mometasone furoate in the treatment of vulvar lichen sclerosus: results of a randomized trial. AB - BACKGROUND: Topical corticosteroids are the first-line treatment for vulvar lichen sclerosus (VLS). However, evidence on the most appropriate treatment regimen is lacking. OBJECTIVES: To compare the effectiveness and tolerability of tapering vs. continuous application of mometasone furoate (MMF) 0.1% ointment in the treatment of active VLS. METHODS: Sixty-four patients with VLS who enrolled in a 12-week active treatment phase were randomized to apply MMF either (i) once daily for 5 days per week for 4 weeks, then on alternate days for 4 weeks, then twice weekly for 4 weeks (group A) or (ii) for five consecutive days per week for the entire treatment duration (group B). The efficacy parameters were the response rate, the proportion of patients achieving an improvement from baseline of >= 75% in subjective and objective scores, and the mean reduction in subjective and objective scores. RESULTS: By the end of the active treatment phase, 27 patients (84%) were considered to be responders in group A, and 25 patients (78%) in group B; 69% and 47% of patients in group A and 62% and 28% in group B achieved >= 75% improvement in subjective and objective scores, respectively. The decreases in mean symptom and sign scores were significant compared with baseline with both regimens. No significant differences were found in any of the assessed efficacy end points between the two treatment protocols. Both regimens were well tolerated. CONCLUSIONS: Both tapering and continuous application of MMF showed similar efficacy and tolerability in the treatment of active VLS, without any difference in patient adherence to therapy. PMID- 26280157 TI - An Evaluation of Educational Neurological Eye Movement Disorder Videos Posted on Internet Video Sharing Sites. AB - BACKGROUND: Internet video sharing sites allow the free dissemination of educational material. This study investigated the quality and educational content of videos of eye movement disorders posted on such sites. METHODS: Educational neurological eye movement videos were identified by entering the titles of the eye movement abnormality into the search boxes of the video sharing sites. Also, suggested links were followed from each video. The number of views, likes, and dislikes for each video were recorded. The videos were then rated for their picture and sound quality. Their educational value was assessed according to whether the video included a description of the eye movement abnormality, the anatomical location of the lesion (if appropriate), and the underlying diagnosis. RESULTS: Three hundred fifty-four of these videos were found on YouTube and Vimeo. There was a mean of 6,443 views per video (range, 1-195,957). One hundred nineteen (33.6%) had no form of commentary about the eye movement disorder shown apart from the title. Forty-seven (13.3%) contained errors in the title or in the text. Eighty (22.6%) had excellent educational value by describing the eye movement abnormality, the anatomical location of the lesion, and the underlying diagnosis. Of these, 30 also had good picture and sound quality. The videos with excellent educational value had a mean of 9.84 "likes" per video compared with 2.37 for those videos without a commentary (P < 0.001). The videos that combined excellent educational value with good picture and sound quality had a mean of 10.23 "likes" per video (P = 0.004 vs videos with no commentary). There was no significant difference in the mean number of "dislikes" between those videos that had no commentary or which contained errors and those with excellent educational value. CONCLUSIONS: There are a large number of eye movement videos freely available on these sites; however, due to the lack of peer review, a significant number have poor educational value due to having no commentary or containing errors. The number of "likes" can help to identify videos with excellent educational value but the number of "dislikes" does not help in discerning which videos have poor educational value. PMID- 26280158 TI - Laser Fabrication of Polymer Ferroelectric Nanostructures for Nonvolatile Organic Memory Devices. AB - Polymer ferroelectric laser-induced periodic surface structures (LIPSS) have been prepared on ferroelectric thin films of a poly(vinylidene fluoride trifluoroethylene) copolymer. Although this copolymer does not absorb light at the laser wavelength, LIPSS on the copolymer can be obtained by forming a bilayer with other light-absorbing polymers. The ferroelectric nature of the structured bilayer was proven by piezoresponse force microscopy measurements. Ferroelectric hysteresis was found on both the bilayer and the laser-structured bilayer. We show that it is possible to write ferroelectric information at the nanoscale. The laser-structured ferroelectric bilayer showed an increase in the information storage density of an order of magnitude, in comparison to the original bilayer. PMID- 26280159 TI - Roma Women's Perspectives on End-of-Life Decisions. AB - Spain's Roma community has its own cultural and moral values. These values influence the way in which end-of-life decision-making is confronted. The objective of this study was to explore the perspective of Roma women on end-of life decision-making. It was a qualitative study involving thirty-three Roma women belonging to groups for training and social development in two municipalities. We brought together five focus groups between February and December 2012. Six mediators each recruited five to six participants. We considered age and care role to be the variables that can have the most influence on opinion regarding end-of-life decision-making. We considered the discussion saturated when the ideas expressed were repeated. Data analysis was carried out according to five steps: describing, organizing, connecting, corroborating/legitimating, and representing the account. The main ideas gleaned from the data were as follows: (1) the important role of the family in end-of life care, especially the role of women; (2) the large influence of community opinion over personal or family decisions, typical of closed societies; (3) the different preferences women had for themselves compared to that for others regarding desired end-of-life care; (4) unawareness or rejection of advance directives. Roma women wish for their healthcare preferences to be taken into account, but "not in writing." The study concluded that the success of end-of life healthcare in Roma families and of their involvement in the making of healthcare decisions depends upon considering and respecting their idiosyncrasy. PMID- 26280160 TI - Psychophysiological evidence for the role of emotion in adaptive memory. AB - Studies demonstrating a mnemonic benefit for encoding words in a survival scenario have revived interest in how human memory is shaped by evolutionary pressures. Prior work on the survival-processing advantage has largely examined cognitive factors as potential proximate mechanisms. The current study, by contrast, focused on the role of perceived threat. Guided by the idea that a survival scenario implies threat, we combined measures of heart rate (HR) with affective ratings to probe the potential presence of fear bradycardia as a marker of freezing--a parasympathetically dominated HR deceleration that reflects the initial stage of the defensive engagement. We replicated the mnemonic advantage in behavior and found that the survival scenario was rated higher in perceived negative arousal than a commonly used control scenario. Critically, words encountered in the survival scenario were associated with more extensive HR deceleration, and this effect was directly related to subsequent recall performance. Our findings point to a role for the involvement of neurobiological fear responses in producing the survival processing advantage, as well as potential links between autonomic changes and cognitive processing in adaptive memory. PMID- 26280161 TI - Post-Traumatic Neuroma After Hair Transplantation. PMID- 26280162 TI - A New Tool to Maximize Donor Harvesting With Safer Closure. AB - BACKGROUND: Scalp laxity is a major factor in achieving the maximum number of grafts in donor harvesting during hair restoration surgery. Proper assessment is important for each individual but especially so in patients presenting tight scalp. OBJECTIVE: To validate cross beam laser (CBL) for scalp laxity assessment in comparison with Mayer elasticity scale (MES). MATERIALS AND METHODS: In a retrospective study of 165 patients, both CBL and MES were used to evaluate scalp laxity in vertical plane at the center and lateral area before surgery. The real width (RW) of donor strip during surgery was considered the gold standard. RESULTS: Spearman correlation coefficient revealed that the CBL width was significantly correlated with the MES width in the following subgroups: (1) subjects undergoing their first session, (2) subsequent session patients, and (3) patients who required maximum number of grafts. Although the CBL width was statistically significant when compared with the RW in certain areas, whereas the MES width was statistically significant in all areas, the differences between the CBL width and the RW were minimal and clinically insignificant. CONCLUSION: The accuracy of scalp laxity measurements using the CBL procedure establishes CBL as a reliable tool for hair restoration surgery. PMID- 26280163 TI - Poly(vinyl pyrrolidone)-assisted hydrothermal synthesis and enhanced visible light photocatalytic performance of oxygen-rich bismuth oxychlorides. AB - A series of novel oxygen-rich bismuth oxychloride (Bi12O17Cl2) were synthesized through a facile poly(vinyl pyrrolidone) (PVP)-assisted hydrothermal route. These obtained Bi12O17Cl2 samples were characterized by various physicochemical techniques. It was found that a proper addition amount of PVP could promote the transformation of Bi12O17Cl2 morphology from irregular clusters to three dimensional hierarchical flower-like microspheres that were nominated as sample BP2. As-synthesized samples were subjected to a photocatalytic degradation of dye Rhodamine B (RhB) or 2,4-dichlorophenol (2,4-DCP) under visible light. Among all candidates, the sample BP2 with a hierarchical flower-like morphology showed the best degradation efficiency for RhB and 2,4-DCP. The apparent rate constant of sample BP2 in terms of degradation of RhB was nearly 5.7 and 45 times that of unmodified BP0 and N-TiO2. The enhanced photocatalytic performance could be ascribed to synergetic effects including unique hierarchical morphologies, large specific surface area, small particle size, good crystallinity, and suitable band structures. A possible mechanism of catalytic degradation was finally proposed basing upon the active species trapping experiments. PMID- 26280164 TI - Moving Forward with School Nutrition Policies: A Case Study of Policy Adherence in Nova Scotia. AB - Many Canadian school jurisdictions have developed nutrition policies to promote health and improve the nutritional status of children, but research is needed to clarify adherence, guide practice-related decisions, and move policy action forward. The purpose of this research was to evaluate policy adherence with a review of online lunch menus of elementary schools in Nova Scotia (NS) while also providing transferable evidence for other jurisdictions. School menus in NS were scanned and a list of commonly offered items were categorized, according to minimum, moderate, or maximum nutrition categories in the NS policy. The results of the menu review showed variability in policy adherence that depended on food preparation practices by schools. Although further research is needed to clarify preparation practices, the previously reported challenges of healthy food preparations (e.g., cost, social norms) suggest that many schools in NS are likely not able to use these healthy preparations, signifying potential noncompliance to the policy. Leadership and partnerships are needed among researchers, policy makers, and nutrition practitioners to address the complexity of issues related to food marketing and social norms that influence school food environments to inspire a culture where healthy and nutritious food is available and accessible to children. PMID- 26280165 TI - Body Mass Index, High-Sensitivity C-Reactive Protein and Mortality in Chinese with Coronary Artery Disease. AB - BACKGROUND: To investigate single and joint associations of body mass index (BMI) and serum high-sensitivity C-reactive protein (hsCRP) with death. METHODS: The study included 1871 coronary artery disease (CAD) patients aged 40-85 year-old recruited from 2008 to 2011. Cox regression models were used to estimate the association of BMI and hsCRP with mortality. The data was analyzed in 2014. RESULTS: During 3.1 years follow-up, 141 deaths were recorded, 110 died of cardiovascular disease (CVD). After adjustment of major CVD risk factors, there was a J-shaped association between BMI and all-cause and CVD mortality, and a positive association between hsCRP and mortality. The J-shaped association of BMI with mortality was present among patients who never smoked or with elevated hsCRP (>=3.0 mg/L). Compared with overweight (BMI 24-27.9 kg/m2) patients with normal hsCRP (<3.0 mg/L), obese patients (BMI>=28 kg/m2) with elevated hsCRP had a 3.41 fold risk of all-cause mortality (95% CI 1.49-7.80) and a 3.50-fold risk of CVD mortality (1.40-8.75), lean patients (BMI<24 kg/m2) with elevated hsCRP concentration had a 2.54-fold risk of all-cause mortality (1.36-4.74) and a 2.36 fold risk of CVD mortality (1.19-4.70). CONCLUSIONS: The association pattern between baseline BMI and mortality changed among different baseline hsCRP concentrations, indicating that low-grade inflammation may be related to BMI and secondary prognosis of CAD. PMID- 26280166 TI - Species Delimitation in the Genus Moschus (Ruminantia: Moschidae) and Its High Plateau Origin. AB - The authenticity of controversial species is a significant challenge for systematic biologists. Moschidae is a small family of musk deer in the Artiodactyla, composing only one genus, Moschus. Historically, the number of species in the Moschidae family has been debated. Presently, most musk deer species were restricted in the Tibetan Plateau and surrounding/adjacent areas, which implied that the evolution of Moschus might have been punctuated by the uplift of the Tibetan Plateau. In this study, we aimed to determine the evolutionary history and delimit the species in Moschus by exploring the complete mitochondrial genome (mtDNA) and other mitochondrial gene. Our study demonstrated that six species, M. leucogaster, M. fuscus, M. moschiferus, M. berezovskii, M. chrysogaster and M. anhuiensis, were authentic species in the genus Moschus. Phylogenetic analysis and molecular dating showed that the ancestor of the present Moschidae originates from Tibetan Plateau which suggested that the evolution of Moschus was prompted by the most intense orogenic movement of the Tibetan Plateau during the Pliocene age, and alternating glacial-interglacial geological eras. PMID- 26280167 TI - Prevalence of cardiovascular risk factors and management practices of acute coronary syndrome in a tertiary care hospital. AB - BACKGROUND: A prospective study of patients with acute coronary syndrome (ACS), who met the inclusion criteria, was carried out. It was conducted in the cardiology department of tertiary care referral hospital in Kerala. An attempt was made to identify and determine the prevalence of cardiovascular risk factors in patients presenting with ACS and to evaluate the current treatment practice pattern of ACS and to compare it with standard treatment guidelines, thereby improving the quality of life of patients. METHODS: Data of patients who met the inclusion criteria were collected in specially designed data collection form. The form included the patient data such as demographics, risk factors, procedures performed during the hospital stay, and in-hospital and discharge drug therapy. Patients with ACS included those with ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina (UA). Descriptive statistics were performed. All statistical analysis was done using Statistical Package for Social Sciences (SPSS) software version 16.0. RESULTS: A total of 100 patients were studied having mean age of 62.57 years+/-12.18 years. Fifty-one percent were having NSTEMI, 33% were having STEMI, and 16% were having UA. Hypertension (63%) and diabetes (51%) were more prevalent in both men and women. Smoking among males was consistently high (48.6%), being highest among adults. Cardiac procedures performed include percutaneous transluminal coronary angioplasty (PTCA) in 45%, coronary angiogram (CAG) in 20%, and coronary artery bypass graft surgery (CABG) in 7%. In-hospital medications were antiplatelets (100%), thrombolytics (28%), statins (97%), anticoagulants (80%), nitrates (73%), beta-blocker (32%), angiotensin-converting enzyme inhibitor (6%), angiotensin receptor blocker (9%), potassium opener (7%), vasodilator (1%), calcium channel blocker (9%), alpha-blocker (7%), and alpha+beta blocker (7%). CONCLUSIONS: The contemporary profile of treatment patterns for patients with ACS indicates an improved adherence to the guidelines. The alarmingly high rate of modifiable risk factors remains a cause of concern and a challenge that needs to be tackled, as better control of cardiovascular risk factors is expected to have a favorable impact on the incidence of ACS. PMID- 26280168 TI - Neuroprotective effect of hydroxy safflor yellow A against cerebral ischemia reperfusion injury in rats: putative role of mPTP. AB - BACKGROUND: Hydroxy safflor yellow A (HSYA) has been translated clinically for cardiovascular diseases. HSYA is also greatly acknowledged for its protective effects against cerebral ischemic-reperfusion (I/R) injury. Although the precise mechanism of cerebral I/R injury is not fully understood, oxygen-derived free radicals and mitochondrial permeability transition pore (mPTP) opening during I/R injury are widely recognized as an important contributor to neuronal injury. Thus, we speculated that the neuroprotective effects of HSYA against cerebral I/R injury may be associated with mPTP modulation. METHODS: Induction of I/R injury was achieved by 60 min of middle cerebral artery occlusion, followed by reperfusion for 24 h. For behavior and cognitive assessment, neurological scoring (NSS), rotarod, and Y-maze task were performed. Oxidative damage was measured in terms of markers such as malondialdehyde, reduced glutathione, and catalase levels and cerebral infarct volumes were quantified using 2,3,5-triphenyl tetrazolinium chloride staining. I/R injury-induced inflammation was determined using tumor necrosis factor-alpha (TNF-alpha) levels. RESULTS: Animals exposed to I/R injury showed neurological severity, functional and cognitive disability, elevated oxidative markers, and TNF-alpha levels along with large infarct volumes. HSYA treatment during onset of reperfusion ameliorated performance in NSS, rotarod and Y-maze attenuated oxidative damage, TNF-alpha levels, and infarction rate. However, treatment with carboxyatractyloside, an mPTP opener, 20 min before HSYA, attenuated the protective effect of HSYA. CONCLUSIONS: Our study confirmed that protective effect of HSYA may be conferred through its free radical scavenger action followed by inhibiting the opening of mPTP during reperfusion and HSYA might act as a promising therapeutic agent against cerebral I/R injury. PMID- 26280169 TI - Immune response modulatory effect of Emilia sonchifolia (L.) DC: an in vivo experimental study. AB - BACKGROUND: This study was performed in order to provide a scientific basis for the conventional use of Emilia sonchifolia in the traditional Indian Ayurvedic medicine possibly through modulation of the host immune defense. METHODS: Emilia sonchifolia methanolic extract (25 mg/kg body weight) was administered intraperitoneally in mice, and hematological parameters, relative organ weights, bone marrow cellularity, and alpha-esterase activity were assessed. Humoral immune response was evaluated by hemagglutinating antibody (HA) titer and plaque forming cell (PFC) assay. Blastogenesis assays of lymphoid organs were done in the presence and absence of various mitogens such as phytohemagglutinin, concanavalin A, pokeweed mitogen, and lipopolysaccharide. Cytotoxic T lymphocyte (CTL) production was assessed by Winn's neutralization test. The levels of cytokines interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were evaluated by ELISA. RESULTS: Emilia sonchifolia significantly enhanced the total white blood cell count (9995+/-535 cells/mm3), bone marrow cellularity, alpha-esterase activity, and weight of lymphoid organs (p<0.001). The effect on humoral immune response was evident from the enhanced HA titer and increased number of PFCs (p<0.001). The blastogenic effects of mitogens were also stimulated to significant levels by E. sonchifolia treatment. Emilia sonchifolia treatment augmented cell-mediated immune response by enhancing the killing activity of CTLs and by enhanced production of IL-2 and IFN-gamma. CONCLUSIONS: From these results, it was very evident that E. sonchifolia, an indigenous medicinal plant, is a potent immune response modulator, and the present report is so far the first study to demonstrate the immunoregulatory activity of E. sonchifolia. PMID- 26280170 TI - Protective effect of dietary fenugreek (Trigonella foenum-graecum) seeds and garlic (Allium sativum) on induced oxidation of low-density lipoprotein in rats. AB - BACKGROUND: Dietary fenugreek seeds (Trigonella foenum-graecum) and garlic (Allium sativum) have been previously observed to have cardioprotective influence in experimentally induced myocardial infarction in rats. Since low-density lipoprotein (LDL) oxidation is a key factor in the arteriosclerotic process, we evaluated their potential in minimizing the LDL oxidation in rats. METHODS: Fenugreek seeds, garlic, and their combination were included along with a high cholesterol diet for 8 weeks. RESULTS: Iron-induced oxidation of LDL in vivo was considerably lowered by dietary fenugreek and garlic. The extent of copper induced oxidation of isolated LDL in vitro was also significantly lesser in fenugreek-fed or fenugreek+garlic-fed rats. Anodic electrophoretic mobility of the oxidized LDL on agarose gel in case of spice-fed animals was decreased and hence consistent with the observed protective influence on LDL oxidation. Dietary fenugreek, garlic, and their combination significantly lowered lipid peroxide levels in plasma, liver, and heart in iron (II)-administered rats. The results suggest that these two dietary spices have protective effect on LDL oxidation under normal situation as well as in hypercholesterolemic situation. The protective effect of the combination of dietary fenugreek and garlic on LDL oxidation both in vivo and in vitro was greater than that of the individual spices. CONCLUSIONS: The protective effect of dietary fenugreek and garlic on LDL oxidation both in vivo and in vitro as evidenced in the present study is suggestive of their cardioprotective potential since LDL oxidation is a key factor in the arteriosclerotic process. PMID- 26280171 TI - The emerging role of the endocannabinoid system in the pathogenesis and treatment of kidney diseases. AB - Endocannabinoids (eCBs) are endogenous lipid ligands that bind to cannabinoid receptors that also mediate the effects of marijuana. The eCB system is comprised of eCBs, anandamide, and 2-arachidonoyl glycerol, their cannabinoid-1 and cannabinoid-2 receptors (CB1 and CB2, respectively), and the enzymes involved in their biosynthesis and degradation. It is present in both the central nervous system and peripheral organs including the kidney. The current review focuses on the role of the eCB system in normal kidney function and various diseases, such as diabetes and obesity, that directly contributes to the development of renal pathologies. Normally, activation of the CB1 receptor regulates renal vascular hemodynamics and stimulates the transport of ions and proteins in different nephron compartments. In various mouse and rat models of obesity and type 1 and 2 diabetes mellitus, eCBs generated in various renal cells activate CB1 receptors and contribute to the development of oxidative stress, inflammation, and renal fibrosis. These effects can be chronically ameliorated by CB1 receptor blockers. In contrast, activation of the renal CB2 receptors reduces the deleterious effects of these chronic diseases. Because the therapeutic potential of globally acting CB1 receptor antagonists in these conditions is limited due to their neuropsychiatric adverse effects, the recent development of peripherally restricted CB1 receptor antagonists may represent a novel pharmacological approach in treating renal diseases. PMID- 26280172 TI - Human Vection Perception Using Inertial Nulling and Certainty Estimation: The Effect of Migraine History. AB - Vection is an illusory perception of self-motion that can occur when visual motion fills the majority of the visual field. This study examines the effect of the duration of visual field movement (VFM) on the perceived strength of self motion using an inertial nulling (IN) and a magnitude estimation technique based on the certainty that motion occurred (certainty estimation, CE). These techniques were then used to investigate the association between migraine diagnosis and the strength of perceived vection. Visual star-field stimuli consistent with either looming or receding motion were presented for 1, 4, 8 or 16s. Subjects reported the perceived direction of self-motion during the final 1s of the stimulus. For the IN method, an inertial nulling motion was delivered during this final 1s of the visual stimulus, and subjects reported the direction of perceived self-motion during this final second. The magnitude of inertial motion was varied adaptively to determine the point of subjective equality (PSE) at which forward or backward responses were equally likely. For the CE trials the same range of VFM was used but without inertial motion and subjects rated their certainty of motion on a scale of 0-100. PSE determined with the IN technique depended on direction and duration of visual motion and the CE technique showed greater certainty of perceived vection with longer VFM duration. A strong correlation between CE and IN techniques was present for the 8s stimulus. There was appreciable between-subject variation in both CE and IN techniques and migraine was associated with significantly increased perception of self-motion by CE and IN at 8 and 16s. Together, these results suggest that vection may be measured by both CE and IN techniques with good correlation. The results also suggest that susceptibility to vection may be higher in subjects with a history of migraine. PMID- 26280173 TI - A Longitudinal Study of Disability, Cognition and Gray Matter Atrophy in Early Multiple Sclerosis Patients According to Evidence of Disease Activity. AB - New treatment options may make "no evidence of disease activity" (NEDA: no relapses or disability progression and no new/enlarging MRI lesions, as opposed to "evidence of disease activity" (EDA) with at least one of the former), an achievable goal in relapsing-remitting multiple sclerosis (RRMS). The objective of the present study was to determine whether early RRMS patients with EDA at one year follow-up had different disability, cognition, treatment and gray matter (GM) atrophy rates from NEDA patients and healthy controls (HC). RRMS patients (mean age 34 years, mean disease duration 2.2 years) were examined at baseline and one-year follow-up with neurological (n = 72), neuropsychological (n = 56) and structural MRI (n = 57) examinations. Matched HC (n = 61) were retested after three years. EDA was found in 46% of RRMS patients at follow-up. EDA patients used more first line and less second line disease modifying treatment than NEDA (p = 0.004). While the patients groups had similar disability levels at baseline, they differed in disability at follow-up (p = 0.010); EDA patients progressed (EDSS: 1.8-2.2, p = 0.010), while NEDA patients improved (EDSS: 2.0-1.7, p<0.001). Cognitive function was stable in both patient groups. Subcortical GM atrophy rates were higher in EDA patients than HC (p<0.001). These results support the relevance of NEDA as outcome in RRMS and indicate that pathological neurodegeneration in RRMS mainly occur in patients with evidence of disease activity. PMID- 26280174 TI - Electronic Properties of Chlorine, Methyl, and Chloromethyl as Substituents to the Ethylene Group--Viewed from the Core of Carbon. AB - "Substituent effects" is an important and useful concept in organic chemistry. Although there are many approaches to parametrizing the electronic and steric effects of substituents, the physical basis for the parameters is often unclear. The purpose of the present work is to explore the properties of chemical shifts in carbon 1s energies as a well-defined basis for characterizing substituents to an ethylene C?C moiety. To this end, high-resolution carbon 1s photoelectron spectra of six chloro-substituted ethenes and seven chloro-substituted propenes have been measured in the gas phase. Site-specific adiabatic ionization energies have been determined from the spectra using theoretical ab initio calculations to predict the vibrational structures. For two molecules, 3-chloropropene and 2,3 dichloropropene, the spectral analyses give quantitative results for the conformer populations. The observed shifts have been analyzed in terms of initial state (potential) and relaxation effects, and charge relaxation has also been analyzed by means of natural resonance theory. On the basis of core-level spectroscopy and models, chlorine, methyl, and chloromethyl have been characterized in terms of their effect on the carbon to which they are attached (alpha site) as well as the neighboring sp(2) carbon (beta site). The derived spectroscopic substituent parameters are characterized by both inductive (electronegativity) effects and the ability of each substituent to engage in electron delocalization via the pi system. Moreover, the adopted approach is extended to include substituent-substituent interaction parameters. PMID- 26280175 TI - Visually induced motion sickness when viewing visual oscillations of different frequencies along the fore-and-aft axis: keeping velocity versus amplitude constant. AB - Exposure to visual oscillations (VOs) can lead to visually induced motion sickness (VIMS). The level of VIMS among viewers has been shown to vary when the frequency of the VOs is changed either by manipulating their amplitude or velocity. The present study investigates whether the level of VIMS would change if we keep the root mean square (rms) velocity or amplitude of VOs constant while manipulating the VO frequency. A total of 25 individuals were exposed to random dot and checkerboard VOs along the fore-and-aft axis in two experiments. Changing the amplitude (or frequency) of VOs while keeping the rms velocity constant did not affect the level of VIMS; however, increasing the rms velocity (or frequency) of VOs while keeping the amplitude constant made VIMS significantly worse. Practitioner Summary: Exposure to VOs of the same frequency can cause different levels of nausea depending on the combination of oscillation amplitude and velocity. Results suggest an opportunity for game designers to reduce symptoms of game sickness by using the correct combinations of velocity and amplitude of the visual motions. PMID- 26280176 TI - Impact of Depression on Risk of Myocardial Infarction, Stroke and Cardiovascular Death in Patients with Psoriasis: A Danish Nationwide Study. AB - Psoriasis is associated with depression, myocardial infarction (MI) and stroke. Patients with depression have increased cardiovascular risk. However, the link between psoriasis, depression and cardiovascular disease is unclear. This link was investigated in a nationwide Danish cohort of patients with psoriasis (n = 29,406). Incidence rates were calculated, and incidence rate ratios (IRRs) adjusted for age, gender, socio-economic status, medication and comorbidity were estimated by Poisson regression models. Risk of MI (IRR 1.57, 95% confidence interval (95% CI) 1.07-2.29), stroke (IRR 1.95, 95% CI 1.43-2.66), and cardiovascular death (IRR 2.24, 95% CI 1.53-3.26) were increased significantly during acute depression, and risk of stroke (IRR 1.51, 95% CI 1.19-1.90) was increased significantly in chronic depression. During remission from depression, only the risk of stroke was increased. In conclusion, in patients with psoriasis, depression is associated with increased risk of MI, stroke and cardiovascular death, especially during acute depression. PMID- 26280178 TI - Analysis of a cancer dormancy model and control of immuno-therapy. AB - The goal of this paper is to analyze a model of cancer-immune system interactions from [16], and to show how the introduction of control in this model can dramatically improve the hypothetical patient response and in effect prevent the cancer from growing. We examine all the equilibrium points of the model and classify them according to their stability properties. We identify an equilibrium point corresponding to a survivable amount of cancer cells which are exactly balanced by the immune response. This situation corresponds to cancer dormancy. By using Lyapunov stability theory we estimate the region of attraction of this equilibrium and propose two control laws which are able to stabilize the system effectively, improving the results of [16]. Ultimately, the analysis presented in this paper reveals that a slower, continuous introduction of antibodies over a short time scale, as opposed to mere inoculation, may lead to more efficient and safer treatments. PMID- 26280177 TI - Caregiver responses to early cleft palate care: A mixed method approach. AB - OBJECTIVE: This study sought to understand caregivers' (CGs') responses to early cleft lip/palate care for their infants. METHOD: A prospective, mixed methods multicenter longitudinal study was conducted among CGs (N = 118) seeking treatment for their infants' cleft lip and palate or cleft lip only at 1 of 6 cleft treatment centers in the United States. Participants were in 1 of 2 treatment groups: traditional care only or nasoalveolar molding (NAM) plus traditional care. The CGs completed semistructured interviews and standardized questionnaires assessing psychosocial well-being and family impact at 3 time points: the beginning of treatment (~1 month of age), prelip surgery (~3-5 months of age), and postpalate surgery (~12-13 months of age). Multilevel modeling was used to longitudinally assess CGs' psychosocial outcomes. RESULTS: Although the first year was demanding for all CGs, NAM onset and the child's lip surgery were particularly stressful times. CGs used optimism, problem-solving behavior, and social support to cope with this stress. Qualitatively, CGs' ability to balance cleft treatment demands with their psychosocial resources and coping strategies influenced family adaptation. Qualitative and quantitative results indicated CGs of NAM-treated infants experienced more rapid declines in anxiety and depressive symptoms and better coping skills over time than CGs whose infants had traditional care. CONCLUSION: CGs of NAM-treated infants experienced more positive psychosocial outcomes than CGs whose infants had traditional care. Results from the mixed model support the family adjustment and adaptation response model as used in pediatric chronic condition research. PMID- 26280179 TI - Ebola outbreak in West Africa: real-time estimation and multiple-wave prediction. AB - Based on the reported data until 18 March 2015 and numerical fitting via a simple formula of cumulative case number, we provide real-time estimation on basic reproduction number, inflection point, peak time and final outbreak size of ongoing Ebola outbreak in West Africa. From our simulation, we conclude that the first wave has passed its inflection point and predict that a second epidemic wave may appear in the near future. PMID- 26280180 TI - Combining robust state estimation with nonlinear model predictive control to regulate the acute inflammatory response to pathogen. AB - The inflammatory response aims to restore homeostasis by means of removing a biological stress, such as an invading bacterial pathogen. In cases of acute systemic inflammation, the possibility of collateral tissue damage arises, which leads to a necessary down-regulation of the response. A reduced ordinary differential equations (ODE) model of acute inflammation was presented and investigated in [10]. That system contains multiple positive and negative feedback loops and is a highly coupled and nonlinear ODE. The implementation of nonlinear model predictive control (NMPC) as a methodology for determining proper therapeutic intervention for in silico patients displaying complex inflammatory states was initially explored in [5]. Since direct measurements of the bacterial population and the magnitude of tissue damage/dysfunction are not readily available or biologically feasible, the need for robust state estimation was evident. In this present work, we present results on the nonlinear reachability of the underlying model, and then focus our attention on improving the predictability of the underlying model by coupling the NMPC with a particle filter. The results, though comparable to the initial exploratory study, show that robust state estimation of this highly nonlinear model can provide an alternative to prior updating strategies used when only partial access to the unmeasurable states of the system are available. PMID- 26280181 TI - Parameters identification for a model of T cell homeostasis. AB - In this study, we consider a model of T cell homeostasis based on the Smith Martin model. This nonlinear model is structured by age and CD44 expression. First, we establish the mathematical well-posedness of the model system. Next, we prove the theoretical identifiability regarding the up-regulation of CD44, the proliferation time phase and the rate of entry into division, by using the experimental data. Finally, we compare two versions of the Smith-Martin model and we identify which model fits the experimental data best. PMID- 26280182 TI - Stochastic modelling of PTEN regulation in brain tumors: A model for glioblastoma multiforme. AB - This work is the outcome of the partnership between the mathematical group of Department DISBEF and the biochemical group of Department DISB of the University of Urbino "Carlo Bo" in order to better understand some crucial aspects of brain cancer oncogenesis. Throughout our collaboration we discovered that biochemists are mainly attracted to the instantaneous behaviour of the whole cell, while mathematicians are mostly interested in the evolution along time of small and different parts of it. This collaboration has thus been very challenging. Starting from [23,24,25], we introduce a competitive stochastic model for post transcriptional regulation of PTEN, including interactions with the miRNA and concurrent genes. Our model also covers protein formation and the backward mechanism going from the protein back to the miRNA. The numerical simulations show that the model reproduces the expected dynamics of normal glial cells. Moreover, the introduction of translational and transcriptional delays offers some interesting insights for the PTEN low expression as observed in brain tumor cells. PMID- 26280183 TI - Order reduction for an RNA virus evolution model. AB - A mathematical or computational model in evolutionary biology should necessary combine several comparatively fast processes, which actually drive natural selection and evolution, with a very slow process of evolution. As a result, several very different time scales are simultaneously present in the model; this makes its analytical study an extremely difficult task. However, the significant difference of the time scales implies the existence of a possibility of the model order reduction through a process of time separation. In this paper we conduct the procedure of model order reduction for a reasonably simple model of RNA virus evolution reducing the original system of three integro-partial derivative equations to a single equation. Computations confirm that there is a good fit between the results for the original and reduced models. PMID- 26280184 TI - Change detection in the dynamics of an intracellular protein synthesis model using nonlinear Kalman filtering. AB - A method for early diagnosis of parametric changes in intracellular protein synthesis models (e.g. the p53 protein - mdm2 inhibitor model) is developed with the use of a nonlinear Kalman Filtering approach (Derivative-free nonlinear Kalman Filter) and of statistical change detection methods. The intracellular protein synthesis dynamic model is described by a set of coupled nonlinear differential equations. It is shown that such a dynamical system satisfies differential flatness properties and this allows to transform it, through a change of variables (diffeomorphism), to the so-called linear canonical form. For the linearized equivalent of the dynamical system, state estimation can be performed using the Kalman Filter recursion. Moreover, by applying an inverse transformation based on the previous diffeomorphism it becomes also possible to obtain estimates of the state variables of the initial nonlinear model. By comparing the output of the Kalman Filter (which is assumed to correspond to the undistorted dynamical model) with measurements obtained from the monitored protein synthesis system, a sequence of differences (residuals) is obtained. The statistical processing of the residuals with the use of x2 change detection tests, can provide indication within specific confidence intervals about parametric changes in the considered biological system and consequently indications about the appearance of specific diseases (e.g. malignancies). PMID- 26280185 TI - Heteroclinic bifurcation for a general predator-prey model with Allee effect and state feedback impulsive control strategy. AB - In this paper, we analyze a general predator-prey model with state feedback impulsive harvesting strategies in which the prey species displays a strong Allee effect. We firstly show the existence of order-1 heteroclinic cycle and order-1 positive periodic solutions by using the geometric theory of differential equations for the unperturbed system. Based on the theory of rotated vector fields, the order-1 positive periodic solutions and heteroclinic bifurcation are studied for the perturbed system. Finally, some numerical simulations are provided to illustrate our main results. All the results indicate that the harvesting rate should be maintained at a reasonable range to keep the sustainable development of ecological systems. PMID- 26280186 TI - Global stability of a multi-group model with vaccination age, distributed delay and random perturbation. AB - A multi-group epidemic model with distributed delay and vaccination age has been formulated and studied. Mathematical analysis shows that the global dynamics of the model is determined by the basic reproduction number R0: the disease-free equilibrium is globally asymptotically stable if R0 <= 1, and the endemic equilibrium is globally asymptotically stable if R0 > 1. Lyapunov functionals are constructed by the non-negative matrix theory and a novel grouping technique to establish the global stability. The stochastic perturbation of the model is studied and it is proved that the endemic equilibrium of the stochastic model is stochastically asymptotically stable in the large under certain conditions. PMID- 26280187 TI - Cilium height difference between strokes is more effective in driving fluid transport in mucociliary clearance: A numerical study. AB - Mucociliary clearance is the first line of defense in our airway. The purpose of this study is to identify and study key factors in the cilia motion that influence the transport ability of the mucociliary system. Using a rod-propel fluid model, we examine the effects of cilia density, beating frequency, metachronal wavelength, and the extending height of the beating cilia. We first verify that asymmetry in the cilia motion is key to developing transport in the mucus flow. Next, two types of asymmetries between the effective and recovery strokes of the cilia motion are considered, the cilium beating velocity difference and the cilium height difference. We show that the cilium height difference is more efficient in driving the transport, and the more bend the cilium during the recovery stroke is, the more effective the transport would be. It is found that the transport capacity of the mucociliary system increases with cilia density and cilia beating frequency, but saturates above by a threshold value in both density and frequency. The metachronal wave that results from the phase lag among cilia does not contribute much to the mucus transport, which is consistent with the experimental observation of Sleigh (1989). We also test the effect of mucus viscosity, whose value is found to be inversely proportional to the transport ability. While multiple parts have to interplay and coordinate to allow for most effective mucociliary clearance, our findings from a simple model move us closer to understanding the effects of the cilia motion on the efficiency of this clearance system. PMID- 26280188 TI - Thermal detection of a prevascular tumor embedded in breast tissue. AB - This paper presents a mathematical model of heat transfer in a prevascular breast tumor. The model uses the steady state temperature of the breast at the skin surface to determine whether there is an underlying tumor and if so, verifies whether the tumor is growing or dormant. The model is governed by the Pennes equations and we present numerical simulations for versions of the model in two and three dimensions. PMID- 26280190 TI - Multi-host transmission dynamics of schistosomiasis and its optimal control. AB - In this paper we formulate a dynamical model to study the transmission dynamics of schistosomiasis in humans and snails. We also incorporate bovines in the model to study their impact on transmission and controlling the spread of Schistosoma japonicum in humans in China. The dynamics of the model is rigorously analyzed by using the theory of dynamical systems. The theoretical results show that the disease free equilibrium is globally asymptotically stable if R0 < 1, and if R0 > 1 the system has only one positive equilibrium. The local stability of the unique positive equilibrium is investigated and sufficient conditions are also provided for the global stability of the positive equilibrium. The optimal control theory are further applied to the model to study the corresponding optimal control problem. Both analytical and numerical results suggest that: (a) the infected bovines play an important role in the spread of schistosomiasis among humans, and killing the infected bovines will be useful to prevent transmission of schistosomiasis among humans; (b) optimal control strategy performs better than the constant controls in reducing the prevalence of the infected human and the cost for implementing optimal control is much less than that for constant controls; and PMID- 26280189 TI - Uncertainty quantification in modeling HIV viral mechanics. AB - We consider an in-host model for HIV-1 infection dynamics developed and validated with patient data in earlier work [7]. We revisit the earlier model in light of progress over the last several years in understanding HIV-1 progression in humans. We then consider statistical models to describe the data and use these with residual plots in generalized least squares problems to develop accurate descriptions of the proper weights for the data. We use recent parameter subset selection techniques [5,6] to investigate the impact of estimated parameters on the corresponding selection scores. Bootstrapping and asymptotic theory are compared in the context of confidence intervals for the resulting parameter estimates. PMID- 26280191 TI - The Electronic Influence of Abasic Sites in DNA. AB - Abasic sites in DNA are prevalent as both naturally forming defects and as synthetic inclusions for biosensing applications. The electronic impact of these defects in DNA sensor and device configurations has yet to be clarified. Here we report the effect of an abasic site on the rate and yield of charge transport through temperature-controlled analysis of DNA duplex monolayers on multiplexed devices. Transport yield through the abasic site monolayer strongly increases with temperature, but the yield relative to an undamaged monolayer decreases with temperature. This is opposite to the increasing relative yield with temperature from a mismatched base pair, and these effects are accounted for by the unique structural impact of each defect. Notably, the effect of the abasic site is nearly doubled when heated from room temperature to 37 degrees C. The rate of transport is largely unaffected by the abasic site, showing Arrhenius-type behavior with an activation energy of ~300 meV. Detailed abasic site investigation elucidates the electrical impact of these biologically spontaneous defects and aids development of biological sensors. PMID- 26280192 TI - Correction to Impact of Coordination Geometry, Bite Angle, and Trans Influence on Metal-Ligand Covalency in Phenyl-Substituted Phosphine Complexes of Ni and Pd. PMID- 26280193 TI - 3D Band Diagram and Photoexcitation of 2D-3D Semiconductor Heterojunctions. AB - The emergence of a rich variety of two-dimensional (2D) layered semiconductor materials has enabled the creation of atomically thin heterojunction devices. Junctions between atomically thin 2D layers and 3D bulk semiconductors can lead to junctions that are fundamentally electronically different from the covalently bonded conventional semiconductor junctions. Here we propose a new 3D band diagram for the heterojunction formed between n-type monolayer MoS2 and p-type Si, in which the conduction and valence band-edges of the MoS2 monolayer are drawn for both stacked and in-plane directions. This new band diagram helps visualize the flow of charge carriers inside the device in a 3D manner. Our detailed wavelength-dependent photocurrent measurements fully support the diagrams and unambiguously show that the band alignment is type I for this 2D-3D heterojunction. Photogenerated electron-hole pairs in the atomically thin monolayer are separated and driven by an external bias and control the "on/off" states of the junction photodetector device. Two photoresponse regimes with fast and slow relaxation are also revealed in time-resolved photocurrent measurements, suggesting the important role played by charge trap states. PMID- 26280194 TI - What Keeps Them Together? Insights into Sex Offender Couples Using Qualitative Content Analyses. AB - Research on sex offenders' relationships is scarce. The aim of this qualitative study was to investigate sex offenders' relationships as well as their female partners' adjustment strategies by means of interview analysis. Both partners profit from the relationship in terms of mutual support and acceptance. The sexual offense is a taboo subject, and the female partners were found to demonstrate cognitive distortions. The imbalance of power found in the sex offenders' relationships is discussed, as is the finding that those sexual offenders interviewed live out their need for dominance and sometimes their aggression. The women interviewed were found to cling to their partners as a result of their insecure attachment style. We discuss couples counseling and therapy as possibilities for addressing the imbalance of power and casting light upon the sexual aspect of the relationship. PMID- 26280195 TI - Hannelore Wass: Death Education--An Enduring Legacy. AB - Hannelore Wass's enduring contribution to the field of thanatology focused on death education In addition to developing a journal initially focused on that topic, Wass also created one of the first text books in the field. This article explores the factors that caused death education to emerge in the late 1960s as well as issues that death education still faces as it continues to evolve. PMID- 26280196 TI - The expanding territories of condensin II. PMID- 26280197 TI - The use of dialdehyde starch derivatives in the phytoremediation of soils contaminated with heavy metals. AB - Products of the reaction between dialdehyde starch and Y-NH2 compounds (e.g. semicarbazide or hydrazine) are effective ligands for metal ions. The usefulness of these derivatives was tested in the experiment, both in terms of the immobilization of heavy metal ions in soil and the potential application in phytoextraction processes. The experimental model comprised maize and the ions of such metals as: Zn(II), Pb(II), Cu(II), Cd(II), and Ni(II). The amount of maize yield, as well as heavy metal content and uptake by the aboveground parts and roots of maize, were studied during a three-year pot experiment. The results of the study indicate the significant impact of heavy metals on reduced yield and increased heavy metal content in maize. Soil-applied dialdehyde starch derivatives resulted in lower yields, particularly disemicarbazone (DASS), but in heavy metal-contaminated soils they largely limited the negative impact of these metals both on yielding and heavy metal content in plants, particularly dihydrazone (DASH). It was demonstrated that the application of dihydrazone (DASH) to a soil polluted with heavy metals boosted the uptake of Zn, Pb, Cu, and Cd from the soil, hence there is a possibility to use this compound in the phytoextraction of these metals from the soil. Decreased Ni uptake was also determined, hence the possibility of using this compound in the immobilization of this metal. The study showed that dialdehyde starch disemicarbazone was ineffective in the discussed processes. PMID- 26280198 TI - Crystal Structures of Escherichia coli Branching Enzyme in Complex with Linear Oligosaccharides. AB - Branching enzyme is responsible for all branching of glycogen and starch. It is an unusual member of the alpha-amylase family because it has both alpha-1,4 amylase activity and alpha-1,6-transferase activity [Drummond, G. S., et al. (1972) Eur. J. Biochem. 26, 168-176]. It also does not react with shorter glucans, though it will bind much longer substrates and substrate mimics [Binderup, K., et al. (2002) Arch. Biochem. Biophys. 397, 279-285]. In an effort to better understand how branching enzyme interacts with its polymeric substrate, we have determined the structure of Delta112 Escherichia coli branching enzyme bound to maltoheptaose and maltohexaose. Together, these structures define six distinct oligosaccharide binding sites on the surface of E. coli branching enzyme. Most of these binding sites surround the edge of the beta-barrel domain and are quite far from the active site. Surprisingly, there is no evidence of oligosaccharide binding in the active site of the enzyme. The closest bound oligosaccharide resides almost 18 A from the active site. Mutations to conserved residues in binding sites I and VI had a debilitating effect on the activity of the enzyme. PMID- 26280199 TI - Self-aligned placement and detection of quantum dots on the tips of individual conical plasmonic nanostructures. AB - Hybrid structures of few or single quantum dots (QDs) coupled to single optical antennas are of prime interest for nano-optical research. The photoluminescence (PL) signal from single nanoemitters, such as QDs, can be enhanced, and their emission characteristics modified, by coupling them to plasmonic nanostructures. Here, a self-aligned technique for placing nanoscale QDs with about 10 nm lateral accuracy and well-defined molecular distances to the tips of individual nanocones is reported. This way the QDs are positioned exactly in the high near-field region that can be created near the cone apex. The cones are excited in the focus of a radially polarized laser beam and the PL signal of few or single QDs on the cone tips is spectrally detected. PMID- 26280200 TI - Intriguing multichannel photoinduced electron transfer in lanthanide(iii) diphenylamine systems. AB - Photoinduced electron transfer (PET) and charge transfer (CT) interactions of trivalent lanthanide ions (Ln(3+)) with a fluorogenic diphenylamine (DPA) donor in aqueous solution have been investigated. Present donor-acceptor systems have a relevance to the leaching out and mitigation of lanthanide ions in the geoenvironment where DPA finds its presence as industrial and agricultural waste. The formation of weak ground state CT complexes in the present systems is confirmed from ground state absorption studies. There is no emissive exciplex formation as evidenced from steady-state (SS) fluorescence measurements. SS fluorescence quenching results, however, indicate substantial static quenching, attributed to ground state complex formation. Time-resolved (TR) fluorescence quenching results show a quite efficient dynamic quenching process. It is established that the TR fluorescence quenching of DPA by lanthanide ions is not due to energy transfer but due to PET from excited DPA to Ln(3+). Direct evidence for the PET mechanism is obtained from laser flash photolysis measurements where a transient absorption band at around 670 nm for the DPA cation is clearly evident. The time constant for DPA cation growth confirms that PET occurs from the excited S1 state of DPA to lanthanide ions. No correlation is, however, observed for the estimated quenching constants with the free energy changes of the PET reactions, due to the participation of multiple PET channels involving vacant electronic states of lanthanide ions. As realized, lanthanide ions are complex electron acceptors in the PET reactions and many extensive follow up studies are expected to understand the details of the multichannel PET in these geologically important redox systems. PMID- 26280202 TI - ADIPOSITY-RELATED CANCER AND FUNCTIONAL IMAGING OF BROWN ADIPOSE TISSUE. AB - OBJECTIVE: Brown adipose tissue (BAT) is involved in energy dissipation and cytokine production and is potentially beneficial for the human body. The aim of the paper is to review the literature on adiposity-related cancer and functional imaging of BAT. METHODS: We performed a review on adiposity-related cancer and functional imaging of BAT. We extensively researched papers for information on BAT molecular biology, as well as functional imaging modalities. RESULTS: Adipose tissue is linked to the development of many cancers. Multiple drugs including fenofibrate, spironolactone, and other substances, as well as experimental agents like beta-3 receptor agonists, caffeine, green tea extract, medium chain triglycerides (MCTs), and adenosine are known to stimulate and activate BAT. However, cold and nonshivering thermogenesis are the main activators of BAT. BAT has been detected on both magnetic resonance imaging (MRI) and 18F fluorodexoxyglucose positron emission tomography (18F-FDG-PET)-based imaging in multiple studies. Different methods of cold stimulation and static and dynamic protocols have been used to detect and image BAT. Factors like sex, fasting or fed state, surface skin temperature, and/or body mass index (BMI) may influence PET-based BAT detection. BAT has also been detected using MRI, (99m)Technetium (Tc)-sestamibi, and 123I-metaiodobenzylguanidine single-photon emission computed tomography/computed tomography (MIBG SPECT/CT). CONCLUSIONS: Stimulation of BAT offers promise in the management of obesity-related conditions. Tracers like [(15)O]-H2O, [(11)C] acetate, and 18F-fluoro-6-thia-heptadecanoic acid (18F-FTHA) that measure BAT blood flow, oxygen utilization, and nonessential fatty acid (NEFA) uptake, respectively, have been studied in humans. Future studies should focus on BAT tissue generation by altering the genetic pathways of adiposity linked genes. PMID- 26280203 TI - SAFETY AND EFFICACY OF A PERI-OPERATIVE PROTOCOL FOR PATIENTS WITH DIABETES TREATED WITH CONTINUOUS SUBCUTANEOUS INSULIN INFUSION WHO ARE ADMITTED FOR SAME DAY SURGERY. AB - OBJECTIVE: The number of people with diabetes using continuous subcutaneous insulin infusions (CSII) with an insulin pump has risen dramatically, creating new challenges when these patients are admitted to the hospital for surgical or other procedures. There is limited literature guiding CSII use during surgical procedures. METHODS: The study was carried out in a large, urban, tertiary care hospital. We enrolled 49 patients using insulin pump therapy presenting for 57 elective surgeries. We developed a CSII peri-operative glycemic management protocol (PGMP) to standardize insulin pump management in patients admitted to a same-day surgery unit (SDSU). The purpose was evaluate the safety (% capillary blood glucose (CBG) <70 mg/dL and/or pump incidents) and efficacy (first postoperative CBG <=200 mg/dL) of the CSII PGMP. We determine the contribution of admission CBG, type of anesthesia, surgery length, and peri-operative steroid use on postoperative glycemic control. RESULTS: Overall, 63% of patients treated according to the CSII PGMP had a first postoperative CBG <=200 mg/dL. There were no episodes of intra- or postoperative hypoglycemia. For patients treated with the CSII PGMP, the mean postoperative CBG was lower in patients with anticipated or actual surgical length <=120 minutes (158.1 +/- 53.9 vs. 216 +/- 77.7 mg/dL, P<.01). No differences were observed with admission CBG, type of anesthesia, or steroid use. CONCLUSIONS: This study demonstrates that a CSII PGMP is both safe and effective for patients admitted for elective surgical procedures and provides an example of a standardized protocol for use in clinical practice. PMID- 26280204 TI - Expression of TNFR2 by regulatory T cells in peripheral blood is correlated with clinical pathology of lung cancer patients. AB - CD4(+)FoxP3(+) regulatory T cells (Tregs) represent a major cellular mediator of cancer immune evasion. The expression of tumor necrosis factor receptor type II (TNFR2) on Tregs is reported to identify the maximally suppressive Treg population in both mice and human. We therefore investigated the phenotype and function of TNFR2(+) Tregs present in the peripheral blood (PB) of 43 lung cancer patients. Further, the association of TNFR2 expression on Tregs with clinicopathological factors was analyzed. The results showed that in the PB of lung cancer patients, Tregs expressed markedly higher levels of TNFR2 than conventional T cells (Tconvs). Expression of TNFR2 appeared to correlate better than CD25(+) and CD127(-) with FoxP3 expression. PB TNFR2(+) Tregs in lung cancer patients were more proliferative and expressed higher levels of the immunosuppressive molecule CTLA-4, and consequently more potently suppressed IFNgamma production by cocultured CD8 CTLs. More importantly, higher TNFR2 expression levels on Tregs were associated with lymphatic invasion, distant metastasis and more advanced clinical stage of lung cancer patients. Therefore, our study suggests that TNFR2(+) Tregs play a role in promoting tumor progressive metastasis and expression of TNFR2 by PB Tregs may prove to be a useful prognostic marker in lung cancer patients. PMID- 26280205 TI - Development of sensitive direct chemiluminescent enzyme immunoassay for the determination of dihydroartemisinin in plasma. AB - Despite significant progress in prevention and therapy, malaria is still one of the world's leading major diseases due to its high morbidity and mortality. Recommended treatments by the World Health Organization include the use of artemisinin and artemisinin derivative-based combination therapies. To allow efficient patient monitoring during antimalarial therapy without the use of expensive apparatus, we developed a sensitive direct chemiluminescent enzyme immunoassay for the determination of dihydroartemisinin in biological fluids. To produce specific antibodies against dihydroartemisinin (DHA), a synthetic DHA derivative was coupled to bovine serum albumin as the immunogen. In parallel, a new, rapid, and efficient procedure to covalently link glycoprotein to all amine containing molecules has been established and the enzyme tracer was prepared by chemically coupling the DHA derivative in combination with SBP rather than the more commonly used HRP. It allowed us to develop, after optimization of the luminescent reagent, a sensitive and stable luminescent EIA, with a LLOQ of 90 pg mL(-1). This assay compares favorably with the most efficient HPLC methods previously reported with a LLOQ close to 1 ng mL(-1) and shows good precision and efficiency since recovery from human plasma spiked with DHA ranged between 91 and 103%, with coefficients of variation of <13%. To date, no immunoassay for DHA has been applied to plasma analysis and this EIA should be very useful in all clinical laboratories for rapid and cost-effective analysis. PMID- 26280206 TI - Simultaneous determination of ten anticoagulant rodenticides in tissues by column switching UHPLC-ESI-MS/MS. AB - This paper describes the development of a method for the simultaneous determination of ten anticoagulant rodenticides (coumafuryl, warfarin, pindone, coumatetralyl, coumachlor, difenacoum, bromadiolone, brodifacoum, chlorophacinone and flocoumafen) in the liver and kidney based on column-switching liquid chromatography coupled with heated electrospray ionization tandem mass spectrometry. The simple sample preparation includes extraction with methanol. A C18 trapping column was used for online solid-phase extraction before analytical separation with the mobile phase comprising a mixture of 0.1% formic acid in water, methanol and acetonitrile. Chromatographic separation was achieved using a Thermo Hypersil ultra high-performance liquid chromatography (UHPLC) C18 column with the mobile phase consisting of 5 mM ammonium formate buffer (pH = 9) and methanol. The column-switching procedure ensured no matrix effects during electrospray ionization (ESI). Extraction recoveries ranged between 91 and 100% for liver and between 89 and 97% for kidney. The method showed good linearity up to 750 ng g(-1). The limit of detection ranged between 0.001 and 0.022 ng g(-1) for liver and between 0.001 and 0.028 ng g(-1) for kidney. The developed method was successfully used in several animal poisoning cases. PMID- 26280207 TI - Quantitative determination of five hydroxy acids, precursors of relevant wine aroma compounds in wine and other alcoholic beverages. AB - A method for the quantitative determination of 2-hydroxy-2-methylbutanoic (2OH2MB), 2-hydroxy-3-methylbutanoic (2OH3MB), 3-hydroxy-3-methylbutanoic (3OH3MB), 2-hydroxy-4-methylpentanoic (2OH4MP) and 3-hydroxybutanoic (3OHB) acids has been optimized, validated and applied to a set of wines and other alcoholic beverages. The analytes were preconcentrated in a solid phase extraction cartridge and derivatized with 2,3,4,5,6-pentafluorobenzyl bromide at room temperature for 30 min, followed by GC-MS analysis. Detection limits were between 0.5 and 29 MUg L(-1), and linearity was maintained up to 3 or 12 mg L(-1), depending on the analyte. Recovery values were between 85 and 106 %, and reproducibility was better than 12 % RSD in most cases. The first specific study of these analytes in wine and other alcoholic beverages is herein reported. Concentrations ranged from the method detection limits to 7820, 519, 8510, 3470 and 2500 MUg L(-1) for 2OH2MB, 2OH3MB, 3OH3MB, 2OH4MP and 3OHB, respectively, which may have relevant sensory effects. These products were not found in distillates (except 3OHB) but were all present in beer. 2OH2MB, 3OH3MB and 3OHB were found in unfermented grape derivatives. Sherry wines had the highest levels of all except for 3OHB. PMID- 26280208 TI - Duration of protective immunity after a single vaccination with a live attenuated bivalent bluetongue vaccine. AB - The prevention of bluetongue is typically achieved with mono- or polyvalent modified- live-attenuated virus (MLV) vaccines. MLV vaccines typically elicit a strong antibody response that correlates directly with their ability to replicate in the vaccinated animal. They are inexpensive, stimulate protective immunity after a single inoculation, and have been proven effective in preventing clinical bluetongue disease. In this study, we evaluated the safety, immunogenicity, and efficacy of a bluetongue vaccine against Bluetongue virus serotypes 4 and 16 in sheep. All the animals remained clinically healthy during the observation period. The vaccinated animals showed no clinical signs except fever (>40.8 degrees C) for 2-4 days. Rapid seroconversion was observed in the sheep, with the accumulation of high antibody titers in the vaccinated animals. No animal became ill after the challenge, indicating that effective protection was achieved. Therefore, this vaccine, prepared from attenuated bluetongue virus strains, is safe, immunogenic, and efficacious. PMID- 26280210 TI - Comparative Immunogenicity of TNF Inhibitors: Impact on Clinical Efficacy and Tolerability in the Management of Autoimmune Diseases. A Systematic Review and Meta-Analysis. AB - BACKGROUND: Tumor necrosis factor (TNF) inhibitors are a mainstay in the treatment of rheumatoid arthritis (RA), as well as in the management of spondyloarthritis (SpA) and inflammatory bowel diseases (IBD). Unfortunately, a portion of patients taking these drugs require escalating doses within the approved label to achieve response, while others lose response altogether. This may be due to the development of antibodies against TNFi agents. OBJECTIVES: Our objective was to examine the immunogenicity of TNF inhibitors (adalimumab, infliximab, etanercept, golimumab, and certolizumab) in RA, SpA, and IBD, and to examine the potential effect of anti-drug antibodies (ADABs) on the loss of clinical response through a systematic literature review and meta-analysis. METHODS: We conducted a comprehensive literature search using three databases (PubMed, Web of Science, and the Cochrane library) to identify studies examining the immunogenicity of TNF inhibitors in autoimmune diseases between 1966 and 31 December 2013. Inclusion criteria required that studies be in English, be randomized controlled trials, observational studies, or case reports involving more than five patients, and that the patients be aged 18 years or older. Studies were excluded if they were strictly genetic with no clinical correlate, if the patients had concomitant cancer within 5 years of the study, or if the patients had a renal disease requiring dialysis. Double extraction was followed by a third extraction if needed. Consensus was reached by discussion when disagreements occurred. Random-effect models were generated for the meta-analysis of 68 studies to estimate the odds ratio (OR) of the ADAB effects on TNF inhibitor response. Regression analysis was used to compare among the drugs and diseases. RESULTS: A total of 68 studies (14,651 patients) matched the inclusion/exclusion criteria. Overall, the cumulative incidence of ADABs was 12.7 % [95 % confidence interval (CI) 9.5-16.7]. Of the patients using infliximab, 25.3 % (95 % CI 19.5-32.3) developed ADABs compared with 14.1 % (95 % CI 8.6-22.3) using adalimumab, 6.9 % (95 % CI 3.4-13.5) for certolizumab, 3.8 % (95 % CI 2.1-6.6) for golimumab, and 1.2 % (95 % CI 0.4-3.8) for etanercept. ADABs reduced the odds of clinical response by 67 % overall, although most of the data were derived from articles involving infliximab (nine) and adalimumab (eight). The summary effect for infliximab yielded an estimated OR (with ADABs vs. without) of 0.42 (95 % CI 0.30 0.58); the summary effect for adalimumab yielded an estimated OR (as above) of 0.13 (95 % CI 0.08-0.22); and the OR (as above) for golimumab was 0.42 (95 % CI 0.22-0.81). All figures were statistically significant. ADABS decreased response by 27 % in RA and 18 % in SpA, both of which were statistically significant. However, the effect of ADABS on response was not statistically significant for IBD when we only included the studies that reported the duration of exposure in the regression analysis. The use of concomitant immunosuppressives (methotrexate, 6-mercaptopurine, azathioprine, and others) reduced the odds of ADAB formation in all patients by 74 %. The OR for risk with immunosuppressives versus without was 0.26 (95 % CI 0.21-0.32). CONCLUSION: ADABs developed in 13 % of patients. All five TNF inhibitors were associated with ADABs, but to varying degrees depending on the specific TNF inhibitor and the disease. ADABs are associated with reduced clinical response and an increased incidence of infusion reactions and injection site reactions. Concomitant use of immunosuppressives can reduce ADAB formation. PMID- 26280209 TI - Intraoperative indocyanine green fluorescence angiography to predict wound complications in complex ventral hernia repair. AB - INTRODUCTION: Complex ventral hernia repair (VHR) is associated with a greater than 30% wound complication rate. Perfusion mapping using indocyanine green fluorescence angiography (ICG-FA) has been demonstrated to predict skin and soft tissue necrosis in many reconstructive procedures; however, it has yet to be evaluated in VHR. METHODS: Patients undergoing complex VHR involving component separation and/or extensive subcutaneous advancement flaps were included in a prospective, blinded study. Patients with active infection were excluded. ICG-FA was performed prior to incision and prior to closure, but the surgeon was not allowed to view it. An additional blinded surgeon documented wound complications and evaluated postoperative photographs. The operative ICG-FA was reviewed blinded, and investigators were then unblinded to determine its ability to predict wound complications. RESULTS: Fifteen consecutive patients were enrolled with mean age of 56.1 years and average BMI of 34.9, of which 60% were female. Most (73.3%) had prior hernia repairs (average of 1.8 prior repairs). Mean defect area was 210.4 cm2, mean OR time was 206 min, 66.6% of patients underwent concomitant panniculectomy, and 40% had component separation. Mean follow-up was 7 months. Two patients developed wound breakdown requiring reoperation, while 1 had significant fat necrosis and another a wound infection, requiring operative intervention. ICG-FA was objectively reviewed and predicted all 4 wound complications. Of the 12 patients without complications, 1 had an area of low perfusion on ICG-FA. This study found a sensitivity of 100% and specificity of 90.9% for predicting wound complications using ICG-FA. CONCLUSION: In complex VHR patients, subcutaneous perfusion mapping with ICG-FA is very sensitive and has the potential to reduce cost and improve patient quality of life by reducing wound complications and reoperation. PMID- 26280211 TI - Predictors of Obesity in a Cohort of Children Enrolled in WIC as Infants and Retained to 3 Years of Age. AB - This longitudinal study of children enrolled as infants in the New York State (NYS) Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) examined predictors of obesity (body mass index >= 95th percentile) at 3 years of age. NYS WIC administrative data which included information from parent interviews and measured heights and weights for children were used. All 50,589 children enrolled as infants in WIC between July to December 2008 and July to December 2009 and retained in WIC through age three were included. At 3 years of age, 15.1% of children were obese. Multiple logistic regression analysis showed that children of mothers who received the Full Breastfeeding Food Package when their infant was enrolled in WIC (adjusted OR = 0.52) and children with <=2 h screen time daily at age 3 (adjusted OR = 0.88) were significantly less likely to be obese (p < 0.001) controlling for race/ethnicity, birth weight, and birthplace. In this cohort of NYS WIC participants, maternal receipt of the Full Breastfeeding Food Package (a surrogate measure of exclusive breastfeeding) is associated with lower levels of obesity in their children at age 3. The relationships between participation in WIC, exclusive breastfeeding, and obesity prevention merit further study. PMID- 26280212 TI - Ulcerative colitis in a patient with non-small-cell lung cancer receiving bevacizumab. AB - Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, is anticipated to prolong survival with inhibition of angiogenesis in patients with non-small-cell lung cancer. Rare life-threatening adverse events affecting the digestive tract have been reported, such as gastrointestinal hemorrhage and bowel perforation. A 62-year-old Japanese woman who was diagnosed as having stage IIIB (cT4N2M0) lung adenocarcinoma received chemotherapy with bevacizumab, pemetrexed and carboplatin every 3 weeks for four cycles, which resulted in a partial response, and then continued with maintenance bevacizumab monotherapy. Fourteen days after completion of the seventh cycle of bevacizumab maintenance therapy, the patient developed sudden abdominal pain with more than 10 episodes of hematochezia per day. On the basis of colonoscopic and pathological findings, ulcerative colitis (UC) with severe pancolitis was diagnosed. This case was unresponsive to medical treatment and required subtotal colectomy for management of the ulcerative colitis. This is the first reported case of ulcerative colitis occurring during bevacizumab therapy. The anti angiogenesis activity of bevacizumab may have been involved in the development and exacerbation of UC in this patient. PMID- 26280214 TI - Isobutanol production from an engineered Shewanella oneidensis MR-1. AB - Shewanella oneidensis MR-1 is one of the most well-known metal-reducing bacteria and it has been extensively studied for microbial fuel cell and bioremediation aspects. In this study, we have examined S. oneidensis MR-1 as an isobutanol producing host by assessing three key factors such as isobutanol synthetic genes, carbon sources, and electron supply systems. Heterologous Ehrlich pathway genes, kivD encoding ketoisovalerate decarboxylase and adh encoding alcohol dehydrogenase, were constructed in S. oneidensis MR-1. Among the composition of carbon sources examined, 2% of N-acetylglucosamine, 1.5% of pyruvate and 2% of lactate were found to be the most optimal nutrients and resulted in 10.3 mg/L of isobutanol production with 48 h of microaerobic incubation. Finally, the effects of metal ions (electron acceptor) and direct electron transfer systems on isobutanol production were investigated, and Fe(2+) ions increased the isobutanol production up to 35%. Interestingly, deletion of mtrA and mtrB, genes responsible for membrane transport systems, did not have significant impact on isobutanol production. Finally, we applied engineered S. oneidensis to a bioelectrical reactor system to investigate the effect of a direct electron supply system on isobutanol production, and it resulted in an increased growth and isobutanol production (up to 19.3 mg/L). This report showed the feasibility of S. oneidensis MR-1 as a genetic host to produce valuable biochemicals and combine an electron supplying system with biotechnological applications. PMID- 26280215 TI - Purification, biochemical characterization and antifungal activity of a novel Aspergillus tubingensis glucose oxidase steady on broad range of pH and temperatures. AB - This study was carried out to evaluate the in vitro and in vivo antifungal efficiency of Aspergillus tubingensis CTM 507 glucose oxidase (GOD) against plant pathogenic fungi. GOD displayed a wide inhibitory spectrum toward different fungi at a concentration of 20 AU. The GOD had a strong inhibitor effect on mycelia growth and spore germination of Pythium ultimum. Interestingly, the GOD exhibited a potent in vivo antifungal effect against P. ultimum responsible for potato plants disease. The antifungal GOD was purified 13-fold with 27 % yield and a specific activity of 3435 U/mg. The relative molecular mass of the GOD was 180 kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The GOD activity was optimum at pH 4.5 and 60 degrees C. It was found to be stable over a large pH range (3-9). It also displayed a marked thermostability with a 50 min half-life at 65 degrees C. The 10 residues of the N-terminal sequence of the purified GOD (S-K-G-S-A-V-T-T-P-D) showed no homology to the other reported GOD, identifying a novel GOD. FTIR spectroscopic analysis revealed the presence of C-O and C=O groups corresponding to a D-glucono-lactone. The findings indicated that GOD is the first A. tubingensis-produced fungicide ever reported to exhibit such promising biological properties. It could become a natural alternative to synthetic fungicides to control certain important plant microbial diseases. PMID- 26280213 TI - Expression Patterns of TRPC1 in Cortical Lesions from Patients with Focal Cortical Dysplasia. AB - Focal cortical dysplasia (FCD) is known as a common cause of chronic refractory epilepsy, but the underlying mechanisms of the factors that lead to FCD-related epilepsy are unclear. Previous studies have shown that canonical transient receptor potential channels (TRPCs) might be involved in the process of epileptogenesis. Canonical transient receptor potential channel 1 (TRPC1), which is ubiquitously expressed in the brain, has been shown to be involved in epileptiform bust firing in knockout mice. In this study, we examined the expression of TRPC1 in FCD type Ia (FCDIa), FCD type IIa (FCDIIa), and FCD type IIb (FCDIIb) surgical specimens from patients and age-matched autopsy control samples. Real-time quantitative PCR and western blotting indicated that TRPC1 mRNA and protein levels were increased in FCDIa, FCDIIa, and FCDIIb samples compared to control samples. Immunohistochemistry results revealed that TRPC1 was mainly distributed in microcolumns, dysmorphic neurons, and balloon cells. Further double immunofluorescent staining showed that TRPC1 was co-localized with glutamatergic and GABAergic markers. Taken together, our results demonstrate that the overexpression and specific cellular location of TRPC1 might be related to the epileptogenesis of FCD. PMID- 26280216 TI - Postural change in volunteers: sympathetic tone determines microvascular response to cardiac preload and output increases. AB - PURPOSE: Microvascular perfusion may be a non-invasive indicator of fluid responsiveness. We aimed to investigate which of the microvascular perfusion parameters truly reflects fluid responsiveness independent of sympathetic reflexes. METHODS: Fifteen healthy volunteers underwent a postural change from head up tilt (HUT) to the supine position, diminishing sympathetic tone, followed by a 30 degrees passive leg raising (PLR) with unaltered tone. Prior to and after the postural changes, stroke volume (SV) and cardiac output (CO) were measured, as well as sublingual microcirculatory perfusion (sidestream dark field imaging), skin perfusion, and oxygenation (laser Doppler flowmetry and reflectance spectroscopy). RESULTS: In responders (subjects with >10 % increase in CO), the HUT to supine change increased CO, SV, and pulse pressure, while heart rate, systemic vascular resistance, and mean arterial pressure decreased. Additionally, microvascular flow index, laser Doppler flow, and microvascular hemoglobin oxygen saturation and concentration also increased. CONCLUSION: When preload and forward flow increase in association with a decrease in sympathetic activity, microvascular blood flow increases in the skin and in the sublingual area. When preload and forward flow increase with little to no change in sympathetic activity, only sublingual functional capillary density increases. Therefore, our results indicate that sublingual functional capillary density is the best parameter to use when evaluating fluid responsiveness independent of changes in sympathetic tone. PMID- 26280217 TI - Cerebral blood flow during HUTT in young patients with orthostatic intolerance. AB - PURPOSE: To investigate patterns of change in cerebral perfusion during head-up tilt testing (HUTT) in children and young adults with autonomic dysfunction. METHODS: We utilized near-infrared spectroscopy (NIRS) to estimate bilateral cerebral perfusion patterns during HUTT in 71 adolescents and young adults with a diagnosis of autonomic dysfunction. In addition, we used transthoracic impedance to measure cardiac stroke volume and thus infer autonomic tone, heart rate, and blood pressure during the test. Cerebral blood-flow wave-patterns were then visually analyzed and associated with clinical symptoms and measures of cardiovascular and autonomic function. RESULTS: Visual analysis of contour changes in head NIRS values during phases of HUTT revealed variable patterns of cerebral blood flow, some specifically associated with severe symptomatology (i.e., syncope). We also observed an inequality in blood flow of the cerebral hemispheres in many patients. Finally, we observed changes in cardiac stroke volume during HUTT, as previously reported, that related to changes in head NIRS. CONCLUSION: These results confirm a decrease in cerebral blood flow during HUTT as assessed by head NIRS in patients with autonomic dysfunction. Specifically, we have profiled the cerebral blood flow contours throughout the phases of HUTT, which add insight into the clinical spectrum of the disorder and may correlate with clinical severity. PMID- 26280219 TI - Prevention of recurrent autonomic dysreflexia: a survey of current practice. AB - OBJECTIVE: There is a dearth of literature on the treatment of chronic recurrent autonomic dysreflexia (AD), a well-known complication of spinal cord injury that can have life-threatening implications. This study sought to identify clinical practices regarding the treatment of AD, both acute and recurrent, in patients with spinal cord injury (SCI). METHODS: Online survey regarding AD management in SCI composed of 11 questions designed to obtain information on respondent characteristics, AD treatment options, and causes of AD. SETTING: Veterans Administration health care system. PARTICIPANTS: Veterans Health Administration National SCI Staff Physicians were sent an electronic email to participate in the anonymous web-based survey. INTERVENTION: None applicable. RESULTS: The response rate was 52%. The most commonly prescribed medications for minor and severe acute manifestations of AD were nitrates. For recurrent AD, clonidine was the most commonly prescribed medication. INTERPRETATION: Anti-hypertensive medications continue to be the mainstay in the management of both acute and chronic recurrent AD. Current literature is lacking in prospective randomized controlled trials investigating the relative efficacy of AD interventions. Evidence-based practice guidelines are necessary to improve clinical care. PMID- 26280218 TI - Association between cardiovagal baroreflex sensitivity and baseline cerebral perfusion of the hippocampus. AB - PURPOSE: A failure to control perfusion pressure due to impaired baroreflex sensitivity (BRS) could potentially cause chronic brain hypoperfusion, leading to cognitive dysfunction. The primary aim of this study was to determine whether BRS was associated with regional cerebral blood flow as measured by MRI arterial spin labeling (ASL) technique. METHODS: Baroreflex sensitivity was measured using the Valsalva maneuver technique in 52 middle-aged normotensive adults (49 +/- 1 years), and phase IV of the Valsalva maneuver was used for analyses. Cerebral perfusion was measured using the ASL MRI technique in 10 pre-determined brain regions of interest. RESULTS: Hippocampal perfusion was correlated with BRS (R (2) = 0.17, P = 0.01). No association was observed between BRS and cerebral perfusion in the other brain regions of interest. Partial correlational analyses revealed that BRS was an important predictor of hippocampal perfusion, explaining 11 % of the variability independent of other covariates. When participants were divided into tertiles of BRS (11.8 +/- 1.9 and 3.5 +/- 0.1 ms/mmHg for the highest and lowest tertiles), regional cerebral perfusion of the hippocampus was significantly lower in the lowest BRS tertile than in the highest tertile (39.1 +/- 4.3 and 60.5 +/- 8.4 ml/100 g/min). CONCLUSIONS: Baroreflex sensitivity in midlife is positively associated with regional cerebral perfusion of the hippocampus, and impaired BRS appears to be related to brain hypoperfusion even in apparently healthy middle-aged adults. Future longitudinal studies based on the present cross-sectional findings may help to further define the relationship between BRS to cognitive dysfunction. PMID- 26280220 TI - Characterization and pharmacologic targeting of EZH2, a fetal retinal protein and epigenetic regulator, in human retinoblastoma. AB - Retinoblastoma (RB) is the most common primary intraocular cancer in children, and the third most common cancer overall in infants. No molecular-targeted therapy for this lethal tumor exists. Since the tumor suppressor RB1, whose genetic inactivation underlies RB, is upstream of the epigenetic regulator EZH2, a pharmacologic target for many solid tumors, we reasoned that EZH2 might regulate human RB tumorigenesis. Histologic and immunohistochemical analyses were performed using an EZH2 antibody in sections from 43 samples of primary, formalin fixed, paraffin-embedded human RB tissue, cryopreserved mouse retina, and in whole cell lysates from human RB cell lines (Y79 and WERI-Rb1), primary human fetal retinal pigment epithelium (RPE) and fetal and adult retina, mouse retina and embryonic stem (ES) cells. Although enriched during fetal human retinal development, EZH2 protein was not present in the normal postnatal retina. However, EZH2 was detected in all 43 analyzed human RB specimens, indicating that EZH2 is a fetal protein expressed in postnatal human RB. EZH2 expression marked single RB cell invasion into the optic nerve, a site of invasion whose involvement may influence the decision for systemic chemotherapy. To assess the role of EZH2 in RB cell survival, human RB and primary RPE cells were treated with two EZH2 inhibitors (EZH2i), GSK126 and SAH-EZH2 (SAH). EZH2i impaired intracellular adenosine triphosphate (ATP) production, an indicator of cell viability, in a time and dose-dependent manner, but did not affect primary human fetal RPE. Thus, aberrant expression of a histone methyltransferase protein is a feature of human RB. This is the first time this mechanism has been implicated for an eye, adnexal, or orbital tumor. The specificity of EZH2i toward human RB cells, but not RPE, warrants further in vivo testing in animal models of RB, especially those EZH2i currently in clinical trials for solid tumors and lymphoma. PMID- 26280221 TI - Novel regenerative peptide TP508 mitigates radiation-induced gastrointestinal damage by activating stem cells and preserving crypt integrity. AB - In recent years, increasing threats of radiation exposure and nuclear disasters have become a significant concern for the United States and countries worldwide. Exposure to high doses of radiation triggers a number of potentially lethal effects. Among the most severe is the gastrointestinal (GI) toxicity syndrome caused by the destruction of the intestinal barrier, resulting in bacterial translocation, systemic bacteremia, sepsis, and death. The lack of effective radioprotective agents capable of mitigating radiation-induced damage has prompted a search for novel countermeasures that can mitigate the effects of radiation post exposure, accelerate tissue repair in radiation-exposed individuals, and prevent mortality. We report that a single injection of regenerative peptide TP508 (rusalatide acetate, Chrysalin) 24 h after lethal radiation exposure (9 Gy, LD100/15) appears to significantly increase survival and delay mortality by mitigating radiation-induced intestinal and colonic toxicity. TP508 treatment post exposure prevents the disintegration of GI crypts, stimulates the expression of adherens junction protein E-cadherin, activates crypt cell proliferation, and decreases apoptosis. TP508 post-exposure treatment also upregulates the expression of DCLK1 and LGR5 markers of stem cells that have been shown to be responsible for maintaining and regenerating intestinal crypts. Thus, TP508 appears to mitigate the effects of GI toxicity by activating radioresistant stem cells and increasing the stemness potential of crypts to maintain and restore intestinal integrity. These results suggest that TP508 may be an effective emergency nuclear countermeasure that could be delivered within 24 h post exposure to increase survival and delay mortality, giving victims time to reach clinical sites for advanced medical treatment. PMID- 26280223 TI - Large-area high-quality 2D ultrathin Mo2C superconducting crystals. AB - Transition metal carbides (TMCs) are a large family of materials with many intriguing properties and applications, and high-quality 2D TMCs are essential for investigating new physics and properties in the 2D limit. However, the 2D TMCs obtained so far are chemically functionalized, defective nanosheets having maximum lateral dimensions of ~10 MUm. Here we report the fabrication of large area high-quality 2D ultrathin alpha-Mo2C crystals by chemical vapour deposition (CVD). The crystals are a few nanometres thick, over 100 MUm in size, and very stable under ambient conditions. They show 2D characteristics of superconducting transitions that are consistent with Berezinskii-Kosterlitz-Thouless behaviour and show strong anisotropy with magnetic field orientation; moreover, the superconductivity is also strongly dependent on the crystal thickness. Our versatile CVD process allows the fabrication of other high-quality 2D TMC crystals, such as ultrathin WC and TaC crystals, which further expand the large family of 2D materials. PMID- 26280222 TI - Partial denervation of sub-basal axons persists following debridement wounds to the mouse cornea. AB - Although sensory reinnervation occurs after injury in the peripheral nervous system, poor reinnervation in the elderly and those with diabetes often leads to pathology. Here we quantify sub-basal axon density in the central and peripheral mouse cornea over time after three different types of injury. The mouse cornea is highly innervated with a dense array of sub-basal nerves that form a spiral called the vortex at the corneal center or apex; these nerves are readily detected within flat mounted corneas. After anesthesia, corneal epithelial cells were removed using either a dulled blade or a rotating burr within an area demarcated centrally with a 1.5 mm trephine. A third wound type, superficial trephination, involved demarcating the area with the 1.5 mm trephine but not removing cells. By 7 days after superficial trephination, sub-basal axon density returns to control levels; by 28 days the vortex reforms. Although axon density is similar to control 14 days after dulled blade and rotating burr wounding, defects in axon morphology at the corneal apex remain. After 14 days, axons retract from the center leaving the sub-basal axon density reduced by 37.2 and 36.8% at 28 days after dulled blade and rotating burr wounding, respectively, compared with control. Assessment of inflammation using flow cytometry shows that persistent inflammation is not a factor in the incomplete reinnervation. Expression of mRNAs encoding 22 regeneration-associated genes involved in axon targeting assessed by QPCR reveals that netrin-1 and ephrin signaling are altered after wounding. Subpopulations of corneal epithelial basal cells at the corneal apex stop expressing ki67 as early as 7 days after injury and by 14 and 28 days after wounding, many of these basal cells undergo apoptosis and die. Although sub basal axons are restored to their normal density and morphology after superficial trephination, sub-basal axon recovery is partial after debridement wounds. The increase in corneal epithelial basal cell apoptosis at the apex observed at 14 days after corneal debridement may destabilize newly reinnervated sub-basal axons and lead to their retraction toward the periphery. PMID- 26280224 TI - Orientational order of motile defects in active nematics. AB - The study of liquid crystals at equilibrium has led to fundamental insights into the nature of ordered materials, as well as to practical applications such as display technologies. Active nematics are a fundamentally different class of liquid crystals, driven away from equilibrium by the autonomous motion of their constituent rod-like particles. This internally generated activity powers the continuous creation and annihilation of topological defects, which leads to complex streaming flows whose chaotic dynamics seem to destroy long-range order. Here, we study these dynamics in experimental and computational realizations of active nematics. By tracking thousands of defects over centimetre-scale distances in microtubule-based active nematics, we identify a non-equilibrium phase characterized by a system-spanning orientational order of defects. This emergent order persists over hours despite defect lifetimes of only seconds. Similar dynamical structures are observed in coarse-grained simulations, suggesting that defect-ordered phases are a generic feature of active nematics. PMID- 26280225 TI - Design principles for solid-state lithium superionic conductors. AB - Lithium solid electrolytes can potentially address two key limitations of the organic electrolytes used in today's lithium-ion batteries, namely, their flammability and limited electrochemical stability. However, achieving a Li(+) conductivity in the solid state comparable to existing liquid electrolytes (>1 mS cm(-1)) is particularly challenging. In this work, we reveal a fundamental relationship between anion packing and ionic transport in fast Li-conducting materials and expose the desirable structural attributes of good Li-ion conductors. We find that an underlying body-centred cubic-like anion framework, which allows direct Li hops between adjacent tetrahedral sites, is most desirable for achieving high ionic conductivity, and that indeed this anion arrangement is present in several known fast Li-conducting materials and other fast ion conductors. These findings provide important insight towards the understanding of ionic transport in Li-ion conductors and serve as design principles for future discovery and design of improved electrolytes for Li-ion batteries. PMID- 26280227 TI - Chemical vapour deposition: Transition metal carbides go 2D. PMID- 26280226 TI - Phage-mediated counting by the naked eye of miRNA molecules at attomolar concentrations in a Petri dish. AB - The ability to count biomolecules such as cancer-biomarker miRNAs with the naked eye is seemingly impossible in molecular diagnostics. Here, we show an ultrasensitive naked-eye-counting strategy for quantifying miRNAs by employing T7 phage-a bacteria-specific virus nanoparticle-as a surrogate. The phage is genetically engineered to become fluorescent and capable of binding a miRNA capturing gold nanoparticle (GNP) in a one-to-one manner. Target miRNAs crosslink the resultant phage-GNP couple and miRNA-capturing magnetic microparticles, forming a sandwich complex containing equimolar phage and miRNA. The phage is then released from the complex and developed into one macroscopic fluorescent plaque in a Petri dish by plating it in a host bacterial medium. Counting the plaques by the naked eye enables the quantification of miRNAs with detection limits of ~3 and ~5 aM for single-target and two-target miRNAs, respectively. This approach offers ultrasensitive and convenient quantification of disease biomarkers by the naked eye. PMID- 26280228 TI - Clinical Spectrum of Encephalitis Associated With Antibodies Against the alpha Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor: Case Series and Review of the Literature. AB - IMPORTANCE: The clinical features of autoimmune encephalitis associated with antibodies against the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR-Abs) remain poorly defined. OBJECTIVES: To describe 7 patients with encephalitis and AMPAR-Abs and to provide a review of the literature on this disease entity. DESIGN, SETTING, AND PARTICIPANTS: The setting was the Centre National de Reference pour les Syndromes Neurologiques Paraneoplasiques (Lyon, France), and participants were 7 consecutive patients diagnosed as having encephalitis and AMPAR-Abs between January 1, 2010, and December 1, 2014. Patients' clinical data were analyzed, with a median follow-up period of 12 months (range, 2-31 months). Relevant articles were identified in the MEDLINE database using the keywords autoimmune encephalitis and AMPA receptor antibodies until February 15, 2015. MAIN OUTCOMES AND MEASURES: Modes of onset, full clinical presentations, and cancer prevalence. RESULTS: The patients included 4 women and 3 men (median age, 56 years). Four main modes of encephalitis onset were observed, including confusion (3 patients), epileptic (1 patient), amnestic (1 patient), and a severe form of fulminant encephalitis (2 patients). In contrast with previous reports, we observed only 1 patient with seizures. Two patients had cancer (1 lung carcinoma and the other thymic carcinoma). Analysis of the literature identified 35 published cases of encephalitis and AMPAR-Abs, including 18 with clinical data. The same modes of encephalitis onset were observed, including confusion (12 patients), epileptic (1 patient), amnestic (3 patients), and fulminant encephalitis (2 patients). Eleven patients were initially seen with a neoplasm (lung, breast, thymoma, or ovary). CONCLUSIONS AND RELEVANCE: The clinical spectrum of AMPAR encephalitis is variable. Cancer was found in 13 of 27 patients (48%) with known cancer status. Most patients are seen with symptoms suggestive of autoimmune limbic encephalitis, although they can be paucisymptomatic or may manifest severe panencephalitis that evolves to a minimally conscious state and diffuse cortical atrophy. Patients suspected of having autoimmune encephalitis should undergo screening for serum and cerebrospinal fluid AMPAR-Abs. PMID- 26280230 TI - Global Health: It Matters Now More Than Ever. PMID- 26280231 TI - Diagnosis and Management of Osteoporosis. AB - Osteoporosis-related fractures affect approximately one in two white women and one in five white men in their lifetime. The impact of fractures includes loss of function, significant costs, and increased mortality. The U.S. Preventive Services Task Force recommends using dual energy x-ray absorptiometry to screen all women 65 years and older, and younger women who have an increased fracture risk as determined by the World Health Organization's FRAX Fracture Risk Assessment Tool. Although guidelines are lacking for rescreening women who have normal bone mineral density on initial screening, intervals of at least four years appear safe. The U.S. Preventive Services Task Force found insufficient evidence to recommend screening for osteoporosis in men; other organizations recommend screening all men 70 years and older. In patients with newly diagnosed osteoporosis, suggested laboratory tests to identify secondary causes include serum 25-hydroxyvitamin D, calcium, creatinine, and thyroid-stimulating hormone. First-line treatment to prevent fractures consists of fall prevention, smoking cessation, moderation of alcohol intake, and bisphosphonate therapy. Clinicians should consider discontinuing bisphosphonate therapy after five years in women without a personal history of vertebral fractures. Raloxifene, teriparatide, and denosumab are alternative effective treatments for certain subsets of patients and for those who are unable to take or whose condition does not respond to bisphosphonates. The need for follow-up bone mineral density testing in patients receiving treatment for osteoporosis is uncertain. PMID- 26280232 TI - Counseling on Early Childhood Concerns: Sleep Issues, Thumb-Sucking, Picky Eating, School Readiness, and Oral Health. AB - Family physicians are often a source of information and advice on early childhood concerns regarding sleep, thumb-sucking/pacifier use, picky eating, school readiness, and oral health. Evidence indicates that family variables are important in the genesis of sleep difficulties, and that traditional behavioral methods are not as effective as previously thought. Attention to family psychosocial well-being, especially maternal functioning, is important in addressing childhood sleep difficulties. Thumb-sucking and pacifier use may be associated with negative consequences if they persist, and referral is recommended after four years of age if appropriate behavioral interventions are ineffective. Picky eating is heavily influenced by environmental factors, and food neophobia is a normal stage of development. The main approaches to childhood eating problems include social modeling of normal eating behaviors, repeated exposures to new foods, and positive mealtime experiences. School readiness focuses on supporting the psychosocial variables that are associated with school success. Reading with the child enhances literacy skills. Quality early childhood education programs are also effective in enhancing school success. Delaying school entry is not beneficial and may be detrimental. School readiness includes the schools' role in supporting the learning needs of all children regardless of their abilities and skills. Oral health is increasingly recognized as an important contributor to overall health. Oral health should be incorporated into well-child visits beginning at the eruption of the first tooth. PMID- 26280233 TI - Sexual Dysfunction in Women: A Practical Approach. AB - Sexual dysfunction in women is a common and often distressing problem that has a negative impact on quality of life and medication compliance. The problem is often multifactorial, necessitating a multidisciplinary evaluation and treatment approach that addresses biological, psychological, sociocultural, and relational factors. Criteria for sexual interest/arousal disorder require the presence of at least three specific symptoms lasting for at least six months. Lifelong anorgasmia may suggest the patient is unfamiliar or uncomfortable with self stimulation or sexual communication with her partner. Delayed or less intense orgasms may be a natural process of aging due to decreased genital blood flow and dulled genital sensations. Genito-pelvic pain/penetration disorder includes fear or anxiety, marked tightening or tensing of the abdominal and pelvic muscles, or actual pain associated with attempts toward vaginal penetration that is persistent or recurrent for at least six months. Treatment depends on the etiology. Estrogen is effective for the treatment of dyspareunia associated with genitourinary syndrome of menopause. Testosterone, with and without concomitant use of estrogen, is associated with improvements in sexual functioning in naturally and surgically menopausal women, although data on long-term risks and benefits are lacking. Bupropion has been shown to improve the adverse sexual effects associated with antidepressant use; however, data are limited. Psychotherapy or sex therapy is useful for management of the psychological, relational, and sociocultural factors impacting a woman's sexual function. Clinicians can address many of these issues in addition to providing education and validating women's sexual health concerns. PMID- 26280234 TI - Discoloration in the Hands. PMID- 26280235 TI - Screening for Hepatitis B Virus Infection in Nonpregnant Adolescents and Adults. PMID- 26280236 TI - Vorapaxar (Zontivity) for the Prevention of Thrombotic Cardiovascular Events. PMID- 26280239 TI - Screening for Speech and Language Delay and Disorders in Children Aged 5 Years or Younger: Recommendation Statement. PMID- 26280240 TI - When Knowing More About a Patient Enables Us to Do Less. PMID- 26280241 TI - One-Pot Selective Homodimerization/Hydrogenation Strategy for Sequential Dicarba Bridge Formation. AB - The installation of interlocked dicarba bridges into peptide sequences requires the development of a regioselective and chemoselective methodology. This manuscript describes a one-pot, chemoselective synthesis of three 2,7 diaminosuberic acid derivatives from an alkyne, a cobalt-carbonyl protected alkyne, and an alkene using metathesis and homogeneous hydrogenation catalysis. PMID- 26280242 TI - Are preoperative blood neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios useful in predicting malignancy in surgically-treated mucin-producing pancreatic cystic neoplasms? AB - INTRODUCTION: The aim of this study was to determine if neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were predictive of malignancy in mucin-producing pancreatic cystic neoplasms (MpPCN). METHODS: One hundred and twenty patients with MpPCN were retrospectively reviewed. Malignant neoplasms were defined as neoplasms harbouring invasive carcinoma or high grade dysplasia. A high NLR and PLR were defined as >=2.551 and >=208.1, respectively. RESULTS: High NLR was significantly associated with symptomatic tumors, larger tumors, solid component, main-duct IPMN, and Sendai high risk category. High PLR was significantly associated with jaundice and Sendai high risk category. On univariate analyses, symptomatic tumors, jaundice, solid component, dilated pancreatic duct, and both a high NLR and PLR were significant predictors of malignant and invasive MpPCN. On multivariate analyses, solid component and dilated pancreatic duct were independent predictors of malignant and invasive MpPCN. PLR was an independent predictor for invasive MpPCN. When MpPCN were stratified by the Fukuoka and Sendai Guidelines, both a high NLR and PLR were significantly associated with malignant neoplasms within the high risk categories. CONCLUSIONS: PLR is an independent predictor of invasive carcinoma. The addition of PLR as a criterion to the FCG and SCG significantly improved the predictive value of these guidelines in detecting invasive neoplasms. PMID- 26280243 TI - Exploring the Impacts of Ordinary Laboratory Alterations During Forensic DNA Processing on Peak Height Variation, Thresholds, and Probability of Dropout. AB - Impacts of validation design on DNA signal were explored, and the level of variation introduced by injection, capillary changes, amplification, and kit lot was surveyed by examining a set of replicate samples ranging in mass from 0.25 to 0.008 ng. The variations in peak height, heterozygous balance, dropout probabilities, and baseline noise were compared using common statistical techniques. Data indicate that amplification is the source of the majority of the variation observed in the peak heights, followed by capillary lots. The use of different amplification kit lots did not introduce variability into the peak heights, heterozygous balance, dropout, or baseline. Thus, if data from case samples run over a significant time period are not available during validation, the validation must be designed to, at a minimum, include the amplification of multiple samples of varying quantity, with known genotype, amplified and run over an extended period of time using multiple pipettes and capillaries. PMID- 26280244 TI - Non-Saccharomyces yeasts protect against epithelial cell barrier disruption induced by Salmonella enterica subsp. enterica serovar Typhimurium. AB - The human gastrointestinal epithelium makes up the largest barrier separating the body from the external environment. Whereas invasive pathogens cause epithelial barrier disruption, probiotic micro-organisms modulate tight junction regulation and improve epithelial barrier function. In addition, probiotic strains may be able to reduce epithelial barrier disruption caused by pathogenic species. The aim of this study was to explore non-Saccharomyces yeast modulation of epithelial cell barrier function in vitro. Benchmarking against established probiotic strains, we evaluated the ability of four nonpathogenic yeast species to modulate transepithelial electrical resistance (TER) across a monolayer of differentiated human colonocytes (Caco-2 cells). Further, we assessed yeast modulation of a Salmonella Typhimurium-induced epithelial cell barrier function insult. Our findings demonstrate distinct patterns of non-Saccharomyces yeast modulation of epithelial cell barrier function. While the established probiotic yeast Saccharomyces boulardii increased TER across a Caco-2 monolayer by 30%, Kluyveromyces marxianus exhibited significantly stronger properties of TER enhancement (50% TER increase). In addition, our data demonstrate significant yeast-mediated modulation of Salmonella-induced epithelial cell barrier disruption and identify K. marxianus and Metschnikowia gruessii as two non Saccharomyces yeasts capable of protecting human epithelial cells from pathogen invasion. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates distinct patterns of non-Saccharomyces yeast modulation of epithelial cell barrier function in vitro. Further, our data demonstrate significant yeast-mediated modulation of Salmonella Typhimurium-induced epithelial cell barrier disruption and identify Kluyveromyces marxianus and Metschnikowia gruessii as two non Saccharomyces yeasts capable of protecting human epithelial cells from pathogen invasion. This study is the first to demonstrate significant non-Saccharomyces yeast-mediated epithelial cell barrier protection from Salmonella invasion, thus encouraging future efforts aimed at confirming the observed effects in vivo and driving further strain development towards novel yeast probiotics. PMID- 26280245 TI - Facile Synthesis of Au Nanoparticles Embedded in an Ultrathin Hollow Graphene Nanoshell with Robust Catalytic Performance. AB - Au nanoparticles (NPs) uniformly embedded into an ultrathin hollow graphene nanoshell (Au@HGN) are synthesized using a facile template-based procedure. The obtained Au@HGN catalyst exhibits robust and stable catalytic performance in the reduction of 4-nitrophenol to 4-aminophenol, compared with that of traditional Au/TiO2 and previously reported Au- and Ag-based catalysts. PMID- 26280246 TI - CHARACTERIZATION AND FUNCTIONAL STUDY OF A PUTATIVE JUVENILE HORMONE DIOL KINASE IN THE COLORADO POTATO BEETLE Leptinotarsa decemlineata (Say). AB - Juvenile hormone diol kinase (JHDK) is an enzyme involved in JH degradation. In the present article, a putative JHDK cDNA (LdJHDK) was cloned from the Colorado potato beetle Leptinotarsa decemlineata. The cDNA consists of 814 bp, containing a 555 bp open reading frame encoding a 184 amino acid protein. LdJHDK reveals a high degree of identity to the previously reported insect JHDKs. It possesses three conserved purine nucleotide-binding elements, and contains three EF-hand motifs (helix-loop-helix structural domains). LdJHDK mRNA was mainly detected in hindgut and Malpighian tubules. Besides, a trace amount of LdJHDK mRNA was also found in thoracic muscles, brain-corpora cardiaca-corpora allata complex, foregut, midgut, ventral ganglia, fat body, epidermis, and hemocytes. Moreover, LdJHDK was expressed throughout all developmental stages. Within the first, second, and third larval instar, the expression levels of LdJHDK were higher just before and right after the molt, and were lower in the intermediate instar. In the fourth larval instar, the highest peak of LdJHDK occurred 56 h after ecdysis. Ingestion of double-stranded RNA (dsRNA) against LdJHDK successfully knocked down the target gene, increased JH titer, and significantly upregulated LdKr-h1 mRNA level. Knockdown of LdJHDK significantly impaired adult emergence. Thus, we provide a line of experimental evidence in L. decemlineata to support that LdJHDK encodes function protein involved in JH degradation. PMID- 26280247 TI - The Effect of a Cardiovascular Polypill Strategy on Pill Burden. AB - AIMS: Recent trials of cardiovascular polypills in high-risk populations show improvements in the use of cardiovascular preventive treatments, compared to usual care. We describe patterns of pill burden in Australian practice, define the impact of polypill therapy on pill burden, and explore how physicians add medication to polypill therapy. METHODS: The Kanyini Guidelines Adherence with the Polypill Study was an open-label trial involving 623 participants in Australia which randomized participants to a polypill strategy (containing a statin, antiplatelet agent, and two blood-pressure-lowering medications) or usual care. Participants either had established cardiovascular disease or were at high calculated risk (>=15% over 5 years). Current medications, daily pill burden, and self-reported use of combination treatment were recorded prior to randomization and at study end. Median pill burden at baseline and study end was compared in both arms. Subgroup analysis of the polypill strategy on trial primary outcomes was conducted by pill burden at baseline. RESULTS: Median total and cardiovascular pill burdens of the polypill group decreased from 7 to 5 and from 4 to 2, respectively (median change -2; IQR -3, 0), with no change in the usual care group (comparison of change; P < 0.001). No change was seen for noncardiovascular medications. Of those still using the polypill at study end, 43.8% were prescribed additional medications; 84.5% of these additional medications were blood-pressure-lowering medications. Within the polypill group, lower pill burden at baseline was associated with greater increases in the use of indicated cardiovascular preventive medications at study end compared to those with higher pill burdens. No trend was observed between the level of baseline pill burden and the effect of poylpill treatment on systolic blood pressure or total cholesterol. CONCLUSION: A cardiovascular polypill in contemporary Australian practice reduces cardiovascular and total pill burdens, despite frequent prescription of additional medications. PMID- 26280248 TI - Preserving the peritoneal membrane in long-term peritoneal dialysis patients. AB - WHAT IS KNOWN AND OBJECTIVE: Peritoneal dialysis (PD) has been widely used by patients with end-stage renal disease. However, chronic exposure of the peritoneal membrane to bioincompatible PD solutions, and peritonitis and uraemia during long-term dialysis result in peritoneal membrane injury and thereby contribute to membrane changes, ultrafiltration (UF) failure, inadequate dialysis and technical failure. Therefore, preserving the peritoneal membrane is important to maintain the efficacy of PD. This article reviews the current literature on therapeutic agents for preserving the peritoneal membrane. METHODS: A literature search of PubMed was conducted using the search terms peritoneal fibrosis, peritoneal sclerosis, membrane, integrity, preserve, therapy and peritoneal dialysis, but not including peritonitis. Published clinical trials, in vitro studies, experimental trials in animal models, meta-analyses and review articles were identified and reviewed for relevance. RESULTS AND DISCUSSION: We focus on understanding how factors cause peritoneal membrane changes, the characteristics and mechanisms of peritoneal membrane changes in patients undergoing PD and the types of therapeutic agents for peritoneal membrane preservation. There have been many investigations into the preservation of the peritoneal membrane, including PD solution improvement, the inhibition of cytokine and growth factor expression using renin-angiotensin-aldosterone system (RAAS) blockade, glycosaminoglycans (GAGs), L-carnitine and taurine additives. In addition, there are potential future therapeutic agents that are still in experimental investigations. WHAT IS NEW AND CONCLUSION: The efficacy of many of the therapeutic agents is uncertain because there are insufficient good-quality clinical studies. Overall membrane preservation and patient survival remain unproven in using more biocompatible PD solutions. With RAAS blockade, results are still inconclusive, as many of the clinical studies were retrospective. With GAGs, L-carnitine and taurine additives, there is no sufficiently long follow-up clinical study with a large sample size to support its efficacy. Therefore, better quality clinical studies within this area should be performed. PMID- 26280249 TI - Decomposition of Organometal Halide Perovskite Films on Zinc Oxide Nanoparticles. AB - Solution processed zinc oxide (ZnO) nanoparticles (NPs) with excellent electron transport properties and a low-temperature process is a viable candidate to replace titanium dioxide (TiO2) as electron transport layer to develop high efficiency perovskite solar cells on flexible substrates. However, the number of reported high-performance perovskite solar cells using ZnO-NPs is still limited. Here we report a detailed investigation on the chemistry and crystal growth of CH3NH3PbI3 perovskite on ZnO-NP thin films. We find that the perovskite films would severely decompose into PbI2 upon thermal annealing on the bare ZnO-NP surface. X-ray photoelectron spectroscopy (XPS) results show that the hydroxide groups on the ZnO-NP surface accelerate the decomposition of the perovskite films. To reduce the decomposition, we introduce a buffer layer in between the ZnO-NPs and perovskite layers. We find that a commonly used buffer layer with small molecule [6,6]-phenyl-C61-butyric acid methyl ester (PC61BM) can slow down but cannot completely avoid the decomposition. On the other hand, a polymeric buffer layer using poly(ethylenimine) (PEI) can effectively separate the ZnO-NPs and perovskite, which allows larger crystal formation with thermal annealing. The power conversion efficiencies of perovskite photovoltaic cells are significantly increased from 6.4% to 10.2% by replacing PC61BM with PEI as the buffer layer. PMID- 26280254 TI - Depression as a risk factor for cognitive impairment in later life: the Health In Men cohort study. AB - BACKGROUND: Depression is an established risk factor for dementia in later life, but it is unclear if this relationship is causal. This study aimed to determine if clinically significant depressive symptoms are likely to be causally related to cognitive impairment in later life. METHODS: Observational cohort study of 4568 men aged 70-89 years living in Perth, Western Australia, who were free of cognitive impairment at the beginning of follow-up. Current clinically significant depressive symptoms were defined by a score of 7 or more on the Geriatric Depression Scale 15 items. Past depression was ascertained via electronic medical records, by self-report or use of antidepressants. A score of 27 or less on the Telephone Interview for Cognitive Status modified or a recorded diagnosis of dementia in electronic medical records established the presence of cognitive impairment. RESULTS: During the 5-year follow-up, 534 men developed cognitive impairment, 811 died and 1455 were lost. The presence of clinically significant depressive symptoms at study entry was associated with increased risk rate (RR) of cognitive impairment (RR = 2.59, 95% confidence interval: 95%CI = 1.57-4.27), death (RR = 5.07, 95%CI = 3.32-7.75) and loss to follow-up (RR = 2.03, 95%CI = 1.32-3.13). These associations remained statistically significant after adjustment for age, country of birth, education, smoking history, and prevalence hypertension, diabetes, coronary heart disease and stroke. History of past clinically significant depressive symptoms was not associated with incident cognitive impairment (RR = 1.09, 95%CI = 0.78-1.52). CONCLUSIONS: The lack of association between past depression and cognitive impairment suggests that the link between depression and cognitive impairment is not causal and that the presence of clinically significant depressive symptoms in later life may herald the onset of cognitive impairment in at least some people. PMID- 26280255 TI - Lateralization of Brain Networks and Clinical Severity in Toddlers with Autism Spectrum Disorder: A HARDI Diffusion MRI Study. AB - Recent diffusion tensor imaging studies in adolescents and children with Autism Spectrum Disorder (ASD) have reported a loss or an inversion of the typical left right lateralization in fronto-temporal regions crucial for sociocommunicative skills. No studies explored atypical lateralization in toddlers and its correlation with clinical severity of ASD. We recruited a cohort of 20 subjects aged 36 months or younger receiving a first clinical diagnosis of ASD (15 males; age range 20-36 months). Patients underwent diffusion MRI (High-Angular Resolution Diffusion Imaging protocol). Data from cortical parcellation were combined with tractography to obtain a connection matrix and diffusion indexes (DI ) including mean fractional anisotropy (DFA ), number of tracts (DNUM ), and total tract length (DTTL ). A laterality index was generated for each measure, and then correlated with the Autism Diagnostic Observation Schedule-Generic (ADOS G) total score. Laterality indexes of DFA were significantly correlated with ADOS G total scores only in two intrafrontal connected areas (correlation was positive in one case and negative in the other). Laterality indexes of DTTL and DNUM showed significant negative correlations (P < 0.05) in six connected areas, mainly fronto-temporal. This study provides first evidence of a significant correlation between brain lateralization of diffusion indexes and clinical severity in toddlers with a first diagnosis of ASD. Significant correlations mainly involved regions within the fronto-temporal circuits, known to be crucial for sociocommunicative skills. It is of interest that all correlations but one were negative, suggesting an inversion of the typical left-right asymmetry in subjects with most severe clinical impairment. PMID- 26280253 TI - Cost-effectiveness analysis of papillary thyroid cancer surveillance. AB - BACKGROUND: The recent overdiagnosis of subclinical, low-risk papillary thyroid cancer (PTC) coincides with a growing national interest in cost-effective health care practices. The aim of this study was to measure the relative cost effectiveness of disease surveillance of low-risk PTC patients versus intermediate- and high-risk patients in accordance with American Thyroid Association risk categories. METHODS: Two thousand nine hundred thirty-two patients who underwent thyroidectomy for differentiated thyroid cancer between 2000 and 2010 were identified from the institutional database; 1845 patients were excluded because they had non-PTC cancer, underwent less than total thyroidectomy, had a secondary cancer, or had <36 months of follow-up. In total, 1087 were included for analysis. The numbers of postoperative blood tests, imaging scans and biopsies, clinician office visits, and recurrence events were recorded for the first 36 months of follow-up. Costs of surveillance were determined with the Physician Fee Schedule and Clinical Lab Fee Schedule of the Centers for Medicare and Medicaid Services. RESULTS: The median age was 44 years (range, 7-83 years). In the first 36 months after thyroidectomy, there were 3, 44, and 22 recurrences (0.8%, 7.8%, and 13.4%) in the low-, intermediate-, and high-risk categories, respectively. The cost of surveillance for each recurrence detected was US $147,819, US $22,434, and US $20,680, respectively. CONCLUSIONS: The cost to detect a recurrence in a low-risk patient is more than 6 and 7 times greater than the cost for intermediate- and high-risk PTC patients. It is difficult to justify this allocation of resources to the surveillance of low-risk patients. Surveillance strategies for the low-risk group should, therefore, be restructured. PMID- 26280256 TI - The Dietary Approaches to Stop Hypertension Diet and New and Recurrent Root Caries Events in Men. AB - OBJECTIVES: To examine the effect of overall dietary quality on number of teeth with new or recurrent root caries events during follow-up (root caries increment). DESIGN: Prospective study with dental examinations approximately every 3 years over 20 years. SETTING: Veterans Affairs Dental Longitudinal Study in greater Boston, Massachusetts, area. PARTICIPANTS: Men aged 47 to 90 (N = 533). MEASUREMENTS: A single calibrated examiner assessed root caries and restorations, calculus, probing pocket depth, and attachment loss on each tooth at each examination. The adjusted root caries increment (root-ADJCI) was computed from new and recurrent root caries events on teeth with recession of 2 mm or more. Dietary information was obtained from food frequency questionnaires. An adherence score was computed by comparing consumption frequency of 10 food groups (fruits, vegetables, total dairy, low-fat dairy, meat, total grains, high-fiber grains, legumes, fats, sweets) from the Dietary Approaches to Stop Hypertension (DASH) diet guidelines. Mean root-ADJCIs were compared according to DASH adherence score quartile using generalized linear negative binomial regression models, controlling for age, number of teeth at risk of root caries, time at risk of root caries, calculus, presence of removable denture, history of dental prophylaxis, body mass index, and smoking status. RESULTS: Men with DASH adherence scores in the highest quartile had a 30% lower mean root-ADJCI (1.86 teeth) than those in the lowest quartile (2.68 teeth) (P = .03). Root-ADJCI was lower with greater adherence to recommendations for vegetables and total grains and greater with greater sugar-sweetened carbonated beverage consumption. Root caries incidence rate did not vary significantly between quartiles. CONCLUSION: A higher-quality diet may reduce root caries risk in older men. PMID- 26280257 TI - Traumatic Brain Injury: A Major Medical Problem That Could Be Treated Using Transcranial, Red/Near-Infrared LED Photobiomodulation. PMID- 26280258 TI - Impact of antipsoriatic therapy on endothelial function. AB - BACKGROUND: Endothelial function (EF) impairment is one of the first events in the process of atherosclerosis, which is known to be associated with psoriasis. Nevertheless, the effect of antipsoriatic treatments, some of them with atherogenic risks, on cardiovascular morbidity and EF is still unclear. OBJECTIVES: To investigate the effect of short-term antipsoriatic treatments on EF values as a potential marker of their effect on cardiovascular morbidity. METHODS: EF was evaluated in 26 patients with moderate-to-severe psoriasis by measuring microvascular blood flow, expressed as the reactive hyperaemia index (RHI), before and after phototherapy (8 weeks) or systemic antipsoriatic treatment (12 weeks). RESULTS: Antipsoriatic intervention was effective (46% achieving >= 75% improvement in Psoriasis Area and Severity Index), while the average RHI did not improve during the study (1.73 +/- 0.48. vs. 1.66 +/- 0.35, average difference -0.12 +/- 0.43, not significant). Patients with baseline preserved EF exhibited a decline in RHI (difference -0.2 +/- 0.4, P = 0.053), while patients with abnormal baseline RHI presented nonsignificant RHI improvement (RHI difference 0.1 +/- 0.2). CONCLUSIONS: There was no positive effect on EF of short-term antipsoriatic treatment. It is possible that a longer period of treatment and EF evaluation would uncover a positive endothelial effect, especially in patients with baseline abnormal EF. PMID- 26280259 TI - The vista paradox: Framing or contrast? AB - The vista paradox is the illusion in which an object seen through a window appears to shrink in apparent size (and appears farther away) as the observer approaches the window. Paradoxically, the distal object appears smaller as its visual angle increases. We investigated the effect in four experiments varying object size, distance, point of fixation, and texture of the frame and of the object. In the first experiment, we tried to confirm the illusion and to test the robustness of the phenomenon. In the second experiment, we manipulated where subjects fixated (on the frame or on the object) as well as the texture of the object and the frame. Fixation was essential for the illusion: fixating the frame led to an apparent shrinking of the object, whereas fixation on the object did not. Texture of the frame intensified the apparent shrinking of the object. In a third experiment, we separated the point of fixation from the frame in a between subjects design. Finally, in Experiment 4, we showed that the paradox does not require a frame, but it requires a fixation on a location different from the object. That is, the window or frame is dispensable for the vista paradox, but fixation is critical. PMID- 26280260 TI - Fearful faces have a sensory advantage in the competition for awareness. AB - Only a subset of visual signals give rise to a conscious percept. Threat signals, such as fearful faces, are particularly salient to human vision. Research suggests that fearful faces are evaluated without awareness and preferentially promoted to conscious perception. This agrees with evolutionary theories that posit a dedicated pathway specialized in processing threat-relevant signals. We propose an alternative explanation for this "fear advantage." Using psychophysical data from continuous flash suppression (CFS) and masking experiments, we demonstrate that awareness of facial expressions is predicted by effective contrast: the relationship between their Fourier spectrum and the contrast sensitivity function. Fearful faces have higher effective contrast than neutral expressions and this, not threat content, predicts their enhanced access to awareness. Importantly, our findings do not support the existence of a specialized mechanism that promotes threatening stimuli to awareness. Rather, our data suggest that evolutionary or learned adaptations have molded the fearful expression to exploit our general-purpose sensory mechanisms. PMID- 26280261 TI - Probability shapes perceptual precision: A study in orientation estimation. AB - Probability is known to affect perceptual estimations, but an understanding of mechanisms is lacking. Moving beyond binary classification tasks, we had naive participants report the orientation of briefly viewed gratings where we systematically manipulated contingent probability. Participants rapidly developed faster and more precise estimations for high-probability tilts. The shapes of their error distributions, as indexed by a kurtosis measure, also showed a distortion from Gaussian. This kurtosis metric was robust, capturing probability effects that were graded, contextual, and varying as a function of stimulus orientation. Our data can be understood as a probability-induced reduction in the variability or "shape" of estimation errors, as would be expected if probability affects the perceptual representations. As probability manipulations are an implicit component of many endogenous cuing paradigms, changes at the perceptual level could account for changes in performance that might have traditionally been ascribed to "attention." PMID- 26280262 TI - Attentional orienting to social and nonsocial cues in early deaf adults. AB - In 2 experiments we investigated attentional orienting to nonpredictive social and nonsocial cues in deaf observers. In Experiment 1a, 22 early deaf adults and 23 hearing controls performed a peripheral shape-discrimination task, while uninformative central gaze cues validly and invalidly cued the location of the target. As an adaptation to the lack of audition, we expected deaf adults to show a larger impact of gaze cuing on attentional orienting compared with hearing controls. However, contrary to our predictions, deaf participants did not respond faster to cued compared with uncued targets (gaze-cuing effect; GCE), and this behavior partly correlated with early sign language acquisition. Experiment 1b showed a reliable GCE in 13 hearing native signers, thus excluding a key role of early sign language acquisition in explaining the lack of GCE in the response times of deaf participants. To test whether the resistance to uninformative central cues extends to nonsocial cues, in Experiment 2 nonpredictive arrow cues were presented to 14 deaf and 14 hearing participants. Both groups of participants showed a comparable arrow-cuing effect. Together, our findings suggest that deafness may selectively limit attentional-orienting triggered by central irrelevant gaze cues. Possible implications for plasticity related to deafness are discussed. PMID- 26280263 TI - Decreasing auditory Simon effects across reaction time distributions. AB - The Simon effect for left-right visual stimuli previously has been shown to decrease across the reaction time (RT) distribution. This decrease has been attributed to automatic activation of the corresponding response, which then dissipates over time. In contrast, for left-right tone stimuli, the Simon effect has not been found to decrease across the RT distribution but instead tends to increase. It has been proposed that automatic activation occurs through visuomotor information transmission, whereas the auditory Simon effect reflects cognitive coding interference and not automatic activation. In 4 experiments, we examined distributions of the auditory Simon effect for RT, percentage error (PE), and an inverse efficiency score [IES = RT/(1 - PE)] as a function of tone frequency and duration to determine whether the activation-dissipation account is also applicable to auditory stimuli. Consistent decreasing functions were found for the RT Simon effect distribution with short-duration tones of low frequency and for the PE and IES Simon effect distributions for all durations and frequency sets. Together, these findings provide robust evidence that left and right auditory stimuli also produce decreasing Simon effect distribution functions suggestive of automatic activation and dissipation of the corresponding response. PMID- 26280264 TI - Sleep and native language interference affect non-native speech sound learning. AB - Adults learning a new language are faced with a significant challenge: non-native speech sounds that are perceptually similar to sounds in one's native language can be very difficult to acquire. Sleep and native language interference, 2 factors that may help to explain this difficulty in acquisition, are addressed in 3 studies. Results of Experiment 1 showed that participants trained on a non native contrast at night improved in discrimination 24 hr after training, while those trained in the morning showed no such improvement. Experiments 2 and 3 addressed the possibility that incidental exposure to perceptually similar native language speech sounds during the day interfered with maintenance in the morning group. Taken together, results show that the ultimate success of non-native speech sound learning depends not only on the similarity of learned sounds to the native language repertoire, but also to interference from native language sounds before sleep. PMID- 26280265 TI - Illumination frame of reference in the object-reviewing paradigm: A case of luminance and lightness. AB - The present study combines the object-reviewing paradigm (Kahneman, Treisman, & Gibbs, 1992) with the checkershadow illusion (Adelson, 1995) to contrast the effects of objects' luminance versus lightness on the object-specific preview benefit. To this end, we manipulated objects' luminance and the amount of illumination given by an informative background scene in experiments. In line with previous studies (Moore, Stephens, & Hein, 2010), there was no object specific preview benefit when objects were presented on a uniformly colored background and luminance switched between objects. In contrast, when objects were presented on the checkershadow illusion background which provided an explanation for the luminance switch, a reliable object-specific preview benefit was observed. This suggests that object correspondence as measured by the object reviewing paradigm can be influenced by scene-induced, perceived lightness of objects' surfaces. We replicated this finding and moreover showed that the scene context only influences the object-specific preview benefit if the objects are perceived as part of the background scene. PMID- 26280266 TI - Towards a resolution of the attentional-capture debate. AB - The relative contributions of stimulus-driven and goal-directed control of attention have been extensively studied by investigating which irrelevant stimuli capture attention. Although much of this research has focused on color-singleton distractors, the circumstances under which these capture attention remain controversial. In search for a target with a unique known color (known-singleton search), whether singletons in an irrelevant color can be successfully ignored is a hotly debated issue. In search for a target that is not a singleton (feature search), no capture by irrelevant-color singletons is typically observed, but a reverse cueing effect was occasionally reported in the spatial-cueing paradigm. In 3 experiments, we resolve these controversies, by showing that the net spatial effect observed in the spatial-cueing paradigm reflects the sum of 3 separate effects. (a) A same-location benefit, which is determined by the match between the cue and the target colors and indexes contingent attentional capture. (b) A same-location cost, which is also determined by the match between the cue and the target colors, but occurs after selection and indexes processes related to visual working memory; and (c) task-dependent capture by singletons that occurs only when the target is consistently a singleton. Crucially, we show that the same location cost is strongly determined by cue exposure duration, which explains previous failures to isolate it. The implications of these findings for the attentional capture debate are discussed. PMID- 26280267 TI - Grasping the sound: Auditory pitch influences size processing in motor planning. AB - Growing evidence shows that individuals consistently match auditory pitch with visual size. For instance, high-pitched sounds are perceptually associated with smaller visual stimuli, whereas low-pitched sounds with larger ones. The present study explores whether this crossmodal correspondence, reported so far for perceptual processing, also modulates motor planning. To address this issue, we carried out a series of kinematic experiments to verify whether actions implying size processing are affected by auditory pitch. Experiment 1 showed that grasping movements toward small/large objects were initiated faster in response to high/low pitches, respectively, thus extending previous findings in the literature to more complex motor behavior. Importantly, auditory pitch influenced the relative scaling of the hand preshaping, with high pitches associated with smaller grip aperture compared with low pitches. Notably, no effect of auditory pitch was found in case of pointing movements (no grasp implied, Experiment 2), as well as when auditory pitch was irrelevant to the programming of the grip aperture, that is, in case of grasping an object of uniform size (Experiment 3). Finally, auditory pitch influenced also symbolic manual gestures expressing "small" and "large" concepts (Experiment 4). In sum, our results are novel in revealing the impact of auditory pitch on motor planning when size processing is required, and shed light on the role of auditory information in driving actions. PMID- 26280268 TI - Dimension-based statistical learning of vowels. AB - Speech perception depends on long-term representations that reflect regularities of the native language. However, listeners rapidly adapt when speech acoustics deviate from these regularities due to talker idiosyncrasies such as foreign accents and dialects. To better understand these dual aspects of speech perception, we probe native English listeners' baseline perceptual weighting of 2 acoustic dimensions (spectral quality and vowel duration) toward vowel categorization and examine how they subsequently adapt to an "artificial accent" that deviates from English norms in the correlation between the 2 dimensions. At baseline, listeners rely relatively more on spectral quality than vowel duration to signal vowel category, but duration nonetheless contributes. Upon encountering an "artificial accent" in which the spectral-duration correlation is perturbed relative to English language norms, listeners rapidly down-weight reliance on duration. Listeners exhibit this type of short-term statistical learning even in the context of nonwords, confirming that lexical information is not necessary to this form of adaptive plasticity in speech perception. Moreover, learning generalizes to both novel lexical contexts and acoustically distinct altered voices. These findings are discussed in the context of a mechanistic proposal for how supervised learning may contribute to this type of adaptive plasticity in speech perception. PMID- 26280270 TI - A dynamic neural field model of temporal order judgments. AB - Temporal ordering of events is biased, or influenced, by perceptual organization figure-ground organization-and by spatial attention. For example, within a region assigned figural status or at an attended location, onset events are processed earlier (Lester, Hecht, & Vecera, 2009; Shore, Spence, & Klein, 2001), and offset events are processed for longer durations (Hecht & Vecera, 2011; Rolke, Ulrich, & Bausenhart, 2006). Here, we present an extension of a dynamic field model of change detection (Johnson, Spencer, Luck, & Schoner, 2009; Johnson, Spencer, & Schoner, 2009) that accounts for both the onset and offset performance for figural and attended regions. The model posits that neural populations processing the figure are more active, resulting in a peak of activation that quickly builds toward a detection threshold when the onset of a target is presented. This same enhanced activation for some neural populations is maintained when a present target is removed, creating delays in the perception of the target's offset. We discuss the broader implications of this model, including insights regarding how neural activation can be generated in response to the disappearance of information. PMID- 26280269 TI - New perspectives on the measurement and time course of auditory enhancement. AB - A target sound can become more audible and may "pop out" from a simultaneously presented masker if the masker is presented first by itself, as a precursor. This phenomenon, known as auditory enhancement, may reflect the general perceptual principle of contrast enhancement, which facilitates adaptation to ongoing acoustic conditions and the detection of new events. Little is known about the mechanisms underlying enhancement, and potential confounding factors have made the size of the effect and its time course a point of contention. Here we measured enhancement as a function of precursor duration and delay between precursor offset and target onset, using 2 single-interval pitch comparison tasks, which involve either same-different or up-down judgments, to avoid the potential confounds of earlier studies. Although these 2 tasks elicit different levels of performance and may reflect different underlying mechanisms, they produced similar amounts of enhancement. The effect decreased with decreasing precursor duration, but remained present for precursors as short as 62.5 ms, and decreased with increasing gap between the precursor and target, but remained measurable 1 s after the precursor. Additional conditions, examining the effect of precursor/masker similarity and the possible role of grouping and cueing, suggest multiple sources of auditory enhancement. PMID- 26280271 TI - Retraction of Anderson et al. (2013). AB - Reports the retraction of "Selection and storage of perceptual groups is constrained by a discrete resource in working memory" by David E. Anderson, Edward K. Vogel and Edward Awh (Journal of Experimental Psychology: Human Perception and Performance, 2013[Jun], Vol 39[3], 824-835). At the request of the authors, the following article from the June 2013 issue is being retracted. (The following abstract of the original article appeared in record 2012-27552-001.) Perceptual grouping can lead observers to perceive a multielement scene as a smaller number of hierarchical units. Past work has shown that grouping enables more elements to be stored in visual working memory (WM). Although this may appear to contradict so-called discrete resource models that argue for fixed item limits in WM storage, it is also possible that grouping reduces the effective number of "items" in the display. To test this hypothesis, we examined how mnemonic resolution declined as the number of items to be stored increased. Discrete resource models predict that precision will reach a stable plateau at relatively early set sizes, because no further items can be stored once putative item limits are exceeded. Thus, we examined whether the precision by set size function was bilinear when storage was enhanced via perceptual grouping. In line with the hypothesis that each perceptual group counted as a single "item," precision still reached a clear plateau at a set size determined by the number of stored groups. Moreover, the maximum number of elements stored was doubled, and electrophysiological measures showed that selection and storage-related neural responses were the same for a single element and a multielement perceptual group. Thus, perceptual grouping allows more elements to be held in working memory while storage is still constrained by a discrete item limit. (PsycINFO Database Record PMID- 26280272 TI - MiR-133b-5p regulates the expression of the heat shock protein 70 during rat neuronal cell apoptosis induced by the gp120 V3 loop peptide. AB - Neuronal cell dysfunction and apoptosis, the main causes of HIV-associated dementia, and its underlying mechanism are important unsolved health problems. Many research reports suggest that miRNAs regulate HIV-1-induced apoptosis. We used the HIV-1 gp120 V3 Loop peptide to induce primary rat cortical neurons apoptosis. Next, we used a microRNA microarray to identify the significant changes of miRNA in the rat cortical neurons treated with the gp120 V3 loop peptide. We used western blot and real-time PCR to measure the regulation of heat shock protein 70 by rno-miR-133b-5p. In response to the gp120 V3 loop peptide treatment, rat cortical neurons exhibited 11 up-regulated and 21 down-regulated miRNAs. We further examined miR-133b-5p, a microRNA that was up-regulated more than 118-fold. In addition, both HSP70 mRNA and protein expression were dose dependent in rats cortical neurons treated with gp120 V3 loop peptide for 48 hr. MiR-133b-5p could regulate heat shock protein 70 (HSP70) at both transcription and translation levels. Rno-miR-133b-5p might be less significant for the gp120 V3 loop peptide induced neuron apoptosis. Thus, we discovered a potential new target for the regulation of HIV-1 gp120- induced apoptosis. PMID- 26280273 TI - Intermittent claudication due to peripheral artery disease: best modern medical and endovascular therapeutic approaches. AB - Peripheral artery disease (PAD) is ubiquitous in the USA and is associated with a high burden of morbidity and mortality. Clinical manifestations of PAD are broad and range from the asymptomatic patient to intermittent claudication (IC) to critical limb ischemia (CLI). The efficacy of non-invasive treatment strategies for PAD has been well documented. These include smoking cessation, supervised exercise programs, and medical therapy. Strategies for invasive management of PAD are more controversial due to variability in the manifestations of PAD including lesion length, location, severity, and clinical presentation. This has made formal comparative effectiveness of interventional therapies in PAD challenging. The current review aims to summarize the most recent clinical research in the field of PAD in patients with IC, with a focus on the latest studies regarding risk factor modification and endovascular revascularization therapies. PMID- 26280274 TI - Examining the Cultural Competence of Third- and Fourth-Year Nutrition Students: A Pilot Study. AB - The purpose of this study was to provide preliminary Canadian research assessing nutrition students' cultural competence and to identify areas for future education initiatives in dietetic education that could ultimately improve dietitians' cultural competence. A mixed-methods study was conducted using a 24 item questionnaire that was administered to students enrolled in third- and fourth-year undergraduate nutrition classes (n = 133). In total, 115 questionnaires were analyzed for quantitative data, and 109 were analyzed for qualitative data. The students scored an overall medium-high level of cultural competence. Out of the 5 areas examined (skills, attitudes, awareness, desires, knowledge), students' multicultural knowledge scores were the lowest. It was found that a lower number of barriers to learning about other cultures were significantly associated with a higher overall cultural competence score, and taking a course in cultural foods significantly increased the students' knowledge and overall cultural competence (P <= 0.05). The qualitative data found that students felt the cultural competence curriculum had gaps and identified several ideas for improvement. In conclusion, this research data provides novel insights into the cultural competence of Canadian dietetic students and additionally supports future research and curriculum development to enhance cultural competence. PMID- 26280275 TI - The rostral prefrontal cortex underlies individual differences in working memory capacity: An approach from the hierarchical model of the cognitive control. AB - Neuroimaging and behavioral evidence has suggested that the lateral prefrontal cortex is involved in individual differences in working memory capacity (WMC). However, few studies have localized the neural structures that differentiate high and low WMC individuals, considering the functional architecture of the prefrontal cortex. The present study aimed to identify a frontal region that underlies individual differences from the perspective of the hierarchical architecture of the frontal cortex. By manipulating an episodic factor of cognitive control (control in selecting an appropriate task set according to a temporal context) and using a parametric modulation analysis, we found that both high- and low- WMC individuals have similar activation patterns in the premotor cortex (BA6, 8), caudal prefrontal cortex (BA44, 45), and frontopolar cortex (BA10, 11), but differed in the rostral part of the prefrontal cortex (BA46/47); high WMC individuals showed greater activation in the higher episodic control condition, whereas low WMC individuals showed reduced activation when episodic control was required. Similar patterns of activation were found in the right inferior parietal and middle/inferior temporal cortices. These results indicate that the rostral prefrontal cortex, which supports episodic cognitive control, possibly by sending a weighting signal toward the inferior parietal and middle/inferior temporal cortices that modulate saliency and sensory processing, underlies individual differences in WMC. Episodic control account, which considers the organization of the prefrontal cortex, fits well with previous findings of individual differences in WMC. PMID- 26280276 TI - Nrf2 activity as a potential biomarker for the pan-epigenetic anticancer agent, RRx-001. AB - Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulatory transcription factor that plays an important role in the antioxidant response pathway against anticancer drug-induced cytotoxic effects. RRx-001 is a new anticancer agent that generates reactive oxygen and nitrogen species, and leads to epigenetic alterations in cancer cells. Here we report the RRx-001 mediated nuclear translocation of Nrf2 and the activation of expression of its downstream enzymes HO-1 and NQO1 in tumor cells. Inhibition of intrinsic Nrf2 expression by Nrf2-specific siRNA increased cell sensitivity to RRx-001. Molecular imaging of tumor cells co-expressing pARE-Firefly luciferase and pCMV-Renilla luciferase mRFP in vitro and in vivo in mice revealed that RRx-001 significantly increased ARE-FLUC signal in cells in a dose- and time-dependent manner, suggesting that RRx-001 is an effective activator of the Nrf2-ARE signaling pathway. The pre treatment level of ARE-FLUC signal in cells, reflecting basal activity of Nrf2, negatively correlated with the tumor response to RRx-001. The results support the concept that RRx-001 activates Nrf2-ARE antioxidant signaling pathways in tumor cells. Hence measurement of Nrf2-mediated activation of downstream target genes through ARE signaling may constitute a useful molecular biomarker for the early prediction of response to RRx-001 treatment, and thereby guide therapeutic decision-making. PMID- 26280278 TI - Quantitative characterization of the interface roughness of (GaIn)As quantum wells by high resolution STEM. AB - The physical properties of semiconductor quantum wells (QW), like (GaIn)As/GaAs, are significantly influenced by the interface morphology. In the present work, high angle annular dark field imaging in (scanning) transmission electron microscopy ((S)TEM), in combination with contrast simulation, is used to address this question at atomic resolution. The (GaIn)As QWs were grown with metal organic vapor phase epitaxy on GaAs (001) substrates under different, precisely controlled conditions. In order to be able to compare different samples, a carefully applied method to gain reliable results from high resolution STEM micrographs was used. The thickness gradient of the TEM samples, caused by sample preparation, was compensated by the intensity of group V atomic columns, where no alloying takes place. After that, the In concentration map was plotted for the investigated regions based on the intensity of the group III atomic columns. The composition maps show that the Indium distribution across the quantum well is not homogeneous. The growth temperature of the QW can greatly influence the composition fluctuation and the interface morphology, with higher growth temperature resulting in larger composition fluctuations in the QWs and slightly wider interfaces, i.e. larger In-segregation. Growth interruptions are shown to significantly homogenize the elemental depth profile especially along the (GaIn)As/GaAs interface and hence have a positive effect on interface smoothness. PMID- 26280277 TI - Going viral: a review of replication-selective oncolytic adenoviruses. AB - Oncolytic viruses have had a tumultuous course, from the initial anecdotal reports of patients having antineoplastic effects after natural viral infections a century ago to the development of current cutting-edge therapies in clinical trials. Adenoviruses have long been the workhorse of virotherapy, and we review both the scientific and the not-so-scientific forces that have shaped the development of these therapeutics from wild-type viral pathogens, turning an old foe into a new friend. After a brief review of the mechanics of viral replication and how it has been modified to engineer tumor selectivity, we give particular attention to ONYX-015, the forerunner of virotherapy with extensive clinical testing that pioneered the field. The findings from those as well as other oncolytic trials have shaped how we now view these viruses, which our immune system has evolved to vigorously attack, as promising immunotherapy agents. PMID- 26280279 TI - Differentiating characteristic microstructural features of cancerous tissues using Mueller matrix microscope. AB - Polarized light imaging can provide rich microstructural information of samples, and has been applied to the detections of various abnormal tissues. In this paper, we report a polarized light microscope based on Mueller matrix imaging by adding the polarization state generator and analyzer (PSG and PSA) to a commercial transmission optical microscope. The maximum errors for the absolute values of Mueller matrix elements are reduced to 0.01 after calibration. This Mueller matrix microscope has been used to examine human cervical and liver cancerous tissues with fibrosis. Images of the transformed Mueller matrix parameters provide quantitative assessment on the characteristic features of the pathological tissues. Contrast mechanism of the experimental results are backed up by Monte Carlo simulations based on the sphere-cylinder birefringence model, which reveal the relationship between the pathological features in the cancerous tissues at the cellular level and the polarization parameters. Both the experimental and simulated data indicate that the microscopic transformed Mueller matrix parameters can distinguish the breaking down of birefringent normal tissues for cervical cancer, or the formation of birefringent surrounding structures accompanying the inflammatory reaction for liver cancer. With its simple structure, fast measurement and high precision, polarized light microscope based on Mueller matrix shows a good diagnosis application prospect. PMID- 26280280 TI - Solvation-Dependent Latency of Photoacid Dissociation and Transient IR Signatures of Protonation Dynamics. AB - We elucidate the characteristic proton pathways and the transient infrared signatures of intermediate complexes during the first picoseconds of photoinduced protonation dynamics of a photoacid (N-methyl-6-hydroxyquinolinium) in aqueous solution from first-principles molecular dynamics simulations. Our results indicate that the typical latency time between photoexcitation and proton dissociation ranges from 1 ps to longer time time scales (~100 ps). The rate limiting step for the actual dissociation of the proton into the solvent is the solvation structure of the first accepting water molecule. The nature of the proton pathway in water (stepwise or concerted) is not unique but determined by the coordination number of the accepting water molecules along the hydrogen bond chain. We find a characteristic uncommon infrared mode at ~1300 cm(-1) of the transient photobase-Eigen cation complex immediately after photodissociation that we predict to be observable experimentally in time-resolved IR spectroscopy. A broad continuous absorption band from 1500 to 2000 cm(-1) arises from the acidic proton imminently before dissociation. PMID- 26280281 TI - Development of an LC-MS/MS method for simultaneous determination of memantine and donepezil in rat plasma and its application to pharmacokinetic study. AB - Recently, a fixed dose combination (FDC) of memantine (MM) and donepezil (DPZ) has been approved for the treatment of Alzheimer's disease (AD). In the present work, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of MM and DPZ was developed and validated in rat plasma over the linearity range of 0.2-400ng/mL using amantadine (AM) as an internal standard. Both the analytes and IS were extracted using one step liquid liquid extraction procedure. The analytes were separated on C18 reversed phase column with mobile phase consisting of a mixture of methanol and 10mM ammonium acetate, pH 5 (92:8 v/v) at a flow rate of 0.7mL/min. The detection of the analytes was done on triple quadrupole mass spectrometer operated in positive electrospray ionization mode (ESI) and quantified using multiple reaction monitoring (MRM). The method was fully validated in terms of linearity, accuracy, precision, recovery, matrix effect, dilution integrity, carry-over effect and stability. The within- and between-run precisions were <10% and accuracy was all within +/-10%. The mean recovery of MM and DPZ was found to be greater than 80%. The % RSD value at higher as well as lower concentration was well within the acceptable range (+/-15%) in all the stability experiments. The method was successfully applied to the oral pharmacokinetics and drug-drug interaction study of MM and DPZ in male Sprague Dawley (SD) rats. PMID- 26280282 TI - Development of reversed-phase high performance liquid chromatography methods for quantification of two isomeric flavones and the application of the methods to pharmacokinetic studies in rats. AB - Isomers 5,7-dihydroxy-3,6,8-trimethoxy-2-phenyl-4H-chromen-4-one (5,7-dihydroxy 3,6,8 trimethoxy flavone) (flavone A) and 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl 4H-chromen-4-one (3,5-dihydroxy-6,7,8-trimethoxy flavone) (flavone B) have recently demonstrated differential antineoplastic activities against pancreatic cancer in vitro. These studies also indicated that these compounds target highly tumorigenic cells while sparing normal cells. The in vivo antitumor activities of these flavones have not been determined, and detection protocols for these compounds are needed to conduct pre-clinical assays following intravenous dosing. Here, we report methods developed using acetonitrile to extract two flavone isomers and corresponding internal standards, celecoxib and diclofenac, from rat plasma. Separation was achieved using a Shimadzu liquid chromatography system with a C18 column and mobile phase acetonitrile/water (60:40 and 70:30 for flavones A and B, respectively) containing 0.2% acetic acid and 0.05% triethylamine at a flow rate of 0.4mL/min and detection at 245nm. Calibration curves ranging from 250 to 2500ng/mL and 2500 to 100,000ng/mL for both flavones were linear (r(2)>=0.99) with the lower limits of quantification being 250ng/mL. Recovery of concentrations 250, 1000, 2500, 5000, and 100,000ng/mL ranged from 87 to 116% and 84 to 103% (n=3) for flavone A and B, respectively. Stability of both flavones after a freezing/thawing cycle yielded a mean peak ratio >=0.92 when compared to freshly extracted samples. Intravenous administration of a 20mg/kg dose in rats yielded half-lives of 83.68+/-56.61 and 107.45+/-53.31min with clearance values of 12.99+/-13.78 and 80.79+/-35.06mL/min/kg for flavones A and B, respectively. PMID- 26280283 TI - The study of grinding patterns and factors influencing the grinding areas during sleep bruxism. AB - OBJECTIVE: The purpose of this study is to investigate the grinding patterns and discuss the factors influencing the position relationship between intercuspal position (ICP) and grinding area during sleep bruxism. METHODS: Lateral condylar inclination, inclination of lateral incisal path and freedom in long centric of thirty subjects were measured. The grinding patterns during sleep bruxism were recorded with a bruxism recording device, BruxChecker. The position relationship between ICP and the grinding area was examined. Spearman's rank correlation coefficient was used for correlation analysis between grinding area and free factors (grinding patterns, freedom in long centric and discrepancy between lateral condylar inclination and inclination of lateral incisal path). RESULTS: All 12 subjects with 0mm-freedom in long centric exhibited that ICP of both sides located within the grinding areas. 4 subjects showed that ICP of both sides located outside the grinding areas. There is a significant correlation between 0mm-freedom in long centric and ICP within the grinding areas (p <0.01). CONCLUSIONS: Freedom in long centric has a significant effect on position relationship between intercuspal position and the grinding area. PMID- 26280284 TI - Halo traction, single-segment circumferential fixation treating cervical tubercular spondylitis with kyphosis. AB - OBJECTIVE: To evaluate the clinical efficacy and feasibility of twenty patients with cervical tubercular spondylitis with kyphosis (CTSK) treated by halo traction, single-segment circumferential instrumented fusion combined anterior debridement, decompression and bone grafting. METHODS: Retrospective review of data on twenty patients who suffered from CTSK admitted to our hospital between January 2007 and December 2012. All of them were performed by halo traction, single-segment circumferential instrumented fusion (anterior titanium plate and posterior pedicle or lateral mass fixation) combined anterior debridement, decompression and titanium mesh cage (TMC) filled with allograft bone particles. X-ray and computed tomographic (CT) images were used to determined sagittal balance and bone fusion. The clinical efficacy was evaluated using statistical analysis about the visual analogue scale (VAS) scores of pain, neurological status according to the Frankel classification and erythrocyte sedimentation rate (ESR), which were collected at certain time. RESULTS: The average follow-up period was 34.1 +/- 7.0 months (24-48 months). In the 20 cases, no obvious postoperative complications related to instrumentation and bone grafting and neurologic function was improved in various degrees. The average pretreatment ESR was 46.4 +/- 21.7 mm/h, which got normal within 3 months in all patients. The average VAS on admission was 6.7 +/- 1.7, which decreased to 1.6 +/- 1.1 postoperatively. All patients got bony fusion within 3.4-5.5 months after surgery. The Cobb angle of 30.8 +/- 10.5 degrees on admission reduced to 2.9 +/- 3.9 degrees performed by preoperative halo traction, became to -5.1 +/- 4.0 degrees after operation and remained at -4.3 +/- 3.8 degrees , with 0.9 +/- 0.7 degrees of correction loss. CONCLUSIONS: Halo traction, single-segment circumferential instrumented fusion combined anterior debridement, decompression and TMC can be an effective and safe treatment method for the treatment of cervical tubercular spondylitis with kyphosis and the preoperative halo traction should be laid on much emphasis. PMID- 26280286 TI - Chronic Kidney Disease and Carotid Atherosclerosis in Patients With Acute Stroke. AB - BACKGROUND AND PURPOSE: Chronic kidney disease (CKD) is increasingly recognized as an independent risk factor for cardiovascular disease and stroke. Our aim was to examine the association between estimated glomerular filtration rate (eGFR) and carotid plaques, stenosis and occlusions, and to assess whether CKD and its severity affect carotid atherosclerosis in a cohort of unselected patients with acute stroke. METHODS: A total of 249 consecutive patients with acute stroke (ischemic or hemorrhagic) were included in this study and baseline eGFR, carotid intima-media thickness (cIMT), and carotid stenosis were evaluated. The eGFR was calculated using the modified Modification of Diet in Renal Disease equation, which was adjusted for data from Chinese CKD patients. An eGFR rate of <60 mL/min/1.73 m was defined as CKD. The cIMT and carotid plaques were detected by carotid ultrasound. RESULTS: CKD, defined as eGFR<60 mL/min/1.73 m, was found in 66 individuals (26.50%). Among the 5 subtypes, the level of low-density lipoprotein cholesterol was significantly higher in the moderate and severe stenosis groups compared with the normal, elevated cIMT and mild stenosis groups (P<0.01). The value of eGFR gradually decreased with increasing degree of carotid stenosis, and the differences between the groups were statistically significant (P<0.01). On linear regression analysis, eGFR was negatively correlated with the degree of carotid stenosis (r=0.03; P<0.05). On ordinal logistic regression analysis, eGFR was an independent risk factor associated with carotid atherosclerosis (1.05; 95% confidence interval, 0.47-1.63). CONCLUSIONS: There was a significant burden of atherosclerosis among individuals with CKD. CKD is an independent predictor of carotid plaques, stenoses, and occlusions in patients with acute stroke. PMID- 26280285 TI - Inactivation of Byssochlamys nivea ascospores in strawberry puree by high pressure, power ultrasound and thermal processing. AB - Byssochlamys nivea is a mold that can spoil processed fruit products and produce mycotoxins. In this work, high pressure processing (HPP, 600 MPa) and power ultrasound (24 kHz, 0.33 W/mL; TS) in combination with 75 degrees C for the inactivation of four week old B. nivea ascospores in strawberry puree for up to 30 min was investigated and compared with 75 degrees C thermal processing alone. TS and thermal processing can activate the mold ascospores, but HPP-75 degrees C resulted in 2.0 log reductions after a 20 min process. For a 10 min process, HPP 75 degrees C was better than 85 degrees C alone in reducing B. nivea spores (1.4 vs. 0.2 log reduction), demonstrating that a lower temperature in combination with HPP is more effective for spore inactivation than heat alone at a higher temperature. The ascospore inactivation by HPP-thermal, TS and thermal processing was studied at different temperatures and modeled. Faster inactivation was achieved at higher temperatures for all the technologies tested, indicating the significant role of temperature in spore inactivation, alone or combined with other physical processes. The Weibull model described the spore inactivation by 600 MPa HPP-thermal (38, 50, 60, 75 degrees C) and thermal (85, 90 degrees C) processing, whereas the Lorentzian model was more appropriate for TS treatment (65, 70, 75 degrees C). The models obtained provide a useful tool to design and predict pasteurization processes targeting B. nivea ascospores. PMID- 26280287 TI - Which Comorbidities and Complications Predict Ischemic Stroke Recovery and Length of Stay? AB - OBJECTIVES: Stroke is the second most common cause of death worldwide and can lead to significant disability and long-term costs. Length of stay (LOS) is the most predictive factor in determining inpatient costs. In the present study, factors that affect disability and LOS among ischemic stroke patients admitted to an urban community hospital and 2 university-based teaching hospitals were assessed. METHODS: Data for consecutive patients with acute ischemic strokes were collected, by reviewing discharge diagnosis International Classification of Diseases codes. A data mining process was used to analyze admission data. Data regarding comorbidities and complications were abstracted by mining the secondary diagnoses for their respective International Classification of Diseases-9 codes. The primary outcome was LOS, calculated from the dates of admission and dates of discharge. The second outcome of interest was disability, which was evaluated by the modified Rankin score at the time of discharge. RESULTS: LOS progressively increased with greater disability. Greater age and higher National Institute of Health Stroke Scale at admission were associated with both higher disability and longer LOS. Presence of congestive heart failure or chronic kidney disease, atrial fibrillation, other arrhythmias (preexisting or new onset), and development of acute renal failure were associated with greater LOS but not greater disability status. Patients with a previous stroke and those that developed urinary tract infection as a complication had higher disability. CONCLUSIONS: Greater age and higher National Institute of Health Stroke Scale at admission were associated with both higher disability and longer LOS. Congestive heart failure, CRF, presence of arrhythmias, and development of acute renal failure were associated with greater LOS. The development of urinary tract infection caused higher disability. PMID- 26280288 TI - Neuromyelitis Optica Spectrum Disorder Associated With Autoimmune Hemolytic Anemia and Lymphoma. AB - Neuromyelitis optica (NMO) is an inflammatory demyelinating disorder characterized by monophasic or recurrent attacks of optic neuritis (ON) and transverse myelitis. NMO spectrum disorders include patients who are seropositive for NMO-IgG antibody and have experienced at least 1 demyelinating attack. NMO has been associated with other autoimmune conditions. We describe a patient diagnosed with autoimmune hemolytic anemia and marginal zone lymphoma, who later developed NMO-IgG seropositive ON. The coexistence of multiple immunologic abnormalities in this patient points to a generalized dysfunction of the humoral immune system. History of autoimmunity should alert the clinician to the possibility of NMO spectrum disorder in a patient presenting with isolated ON. PMID- 26280289 TI - Contrasts Between Patients With Lewy Body Dementia Syndromes and APOE epsilon3/epsilon3 Patients With Late-onset Alzheimer Disease Dementia. AB - INTRODUCTION: Neuropsychiatric and epidemiological patterns may compensate for insufficient specificity of diagnostic criteria of Lewy body dementia (LBD) syndromes in differential analysis with Alzheimer disease (AD) dementia. We aimed to compare and distinguish demographic and neuropsychiatric features between LBD and APOE-epsilon3/epsilon3 late-onset AD. METHODS: A total of 39 consecutive patients with Parkinson disease dementia or dementia with Lewy bodies were matched with 39 APOE-epsilon3/epsilon3 patients with late-onset AD according to sex and Mini-Mental State Examination scores, and evaluated for education, age at disease onset, lifetime sanitary conditions, anthropometric measures, alcohol use, smoking, history of head trauma or bacterial infections, family history of neurodegenerative diseases, caregiver burden, functional independence, cognitive decline, neuropsychiatric symptoms, and pharmacological treatment. RESULTS: Family history of parkinsonism and worse motor performance were more prevalent in Parkinson disease dementia, also impacting sleep satisfaction and physical self maintenance. Patients with AD had higher systolic blood pressure, were more independent, and had better performance in visuospatial tasks and calculations, whereas patients with LBD were more oriented and previously lived longer in rural areas without sanitation. Among neuropsychiatric symptoms, hallucinations, apathy, dysphoria, anxiety, and aberrant motor behavior were the most significant for discrimination amidst dementia diagnoses. CONCLUSIONS: Functional performance, visuospatial skills, and behavioral symptoms are helpful for differential diagnoses between LBD and AD. Cerebrovascular risk might be more important for AD pathogenesis, whereas environmental factors might impact development of LBD. PMID- 26280290 TI - Risk of Gastrointestinal Events During Vandetanib Therapy in Patients With Cancer: A Systematic Review and Meta-analysis of Clinical Trials. AB - Vandetanib, a tyrosine kinase inhibitor used as an anticancer therapeutic agent, has adverse events associated with treatment resulting in noncompliance and withdrawal from the therapy. Here, we performed meta-analysis of published clinical trials to determine relative risk (RR) and incidence of gastrointestinal events during vandetanib therapy in patients with cancer. A comprehensive literature search was performed and summary incidence, RR, and 95% confidence intervals (CIs) were calculated employing fixed- or random-effects models, depending on the heterogeneity of trials. Twenty-two trials with 6382 patients were included summary incidences of all-grade gastrointestinal events in patients with cancer were anorexia 24% (95% CI, 20%-28%), constipation 17% (95% CI, 13% 20%), diarrhea 46% (95% CI, 40%-53%), nausea 29% (95% CI, 25%-33%), and vomiting 17% (95% CI, 14%-21%). Incidences of vandetanib-associated gastrointestinal events stratified by tumor histology were statistically insignificant. Vandetanib was associated with a significant risk of all-grade diarrhea (RR 1.75, 95% CI, 1.42-2.16) and high-grade diarrhea (RR 1.94, 95% CI, 1.43-2.64) and significantly decreased risk of all-grade constipation (RR 0.80, 95% CI, 0.71-0.91). Summary RR showed a significant risk of vandetanib-associated constipation (RR 0.82, 95% CI, 0.72-0.93) and diarrhea (all-grade: RR 1.68, 95% CI, 1.31-2.14 and high-grade: RR 1.57, 95% CI, 1.14-2.17) in patients with non-small-cell lung cancer. This study revealed a significantly increased risk of diarrhea and a reduced risk of constipation in patients with cancer receiving vandetanib, suggesting that appropriate and frequent clinical monitoring should be emphasized. PMID- 26280291 TI - Etanercept for the Treatment of Transplantation-Related Lung Injury After Hematopoietic Stem Cell Transplantation. AB - Although some data suggest favorable outcomes with use of etanercept for treatment of transplantation-related lung injury, concerns, such as development of new infections, still exist. The objective of this study was to describe the usage of etanercept at our institution and to evaluate the efficacy and safety of etanercept for this indication. Adult patients receiving at least one dose of etanercept for the treatment of pulmonary complications in patients after hematopoietic stem cell transplant from January 2005 to December 2010 were retrospectively evaluated. Outcomes included hospital mortality, incidence of new infection after etanercept administration, and time from administration of first dose of etanercept to infection. Seventeen patients who received etanercept at our institution from January 2005 to December 2010 were included. Four patients (24%) survived their hospital stay, and 3 patients (18%) were alive at both 100 days and 1 year from the initiation of etanercept therapy. Four patients (24%) developed at least one confirmed new infection after the initiation of etanercept therapy. Both moderate and long-term survival in our cohort was low. Caution and careful assessment of the risks and benefits of therapy should be taken before initiation of etanercept for transplantation-related lung injury. PMID- 26280292 TI - Preadmission Use of Calcium Channel Blockers and Outcomes After Hospitalization With Pneumonia: A Retrospective Propensity-Matched Cohort Study. AB - In sepsis, an overwhelming immune response, as mediated by the release of various inflammatory mediators, can lead to shock, multiple organ damage, and even death. Pneumonia is the leading cause of sepsis. In animal septic models, sepsis could induce uncontrolled calcium (Ca) leaking, raising cytosolic Ca to a toxic level, causing irreversible cellular injuries and organ failure. All types of calcium channel blockers (CCBs), by inhibiting Ca influx, have been shown to decrease overall mortality in various septic animal models. However, to our best knowledge, no clinical study had been conducted to investigate the beneficial effect(s) of CCBs in sepsis. We conducted a retrospective propensity-matched cohort study after screening 2214 patients hospitalized for pneumonia from year 2012 to 2014 at our institution. We identified 387 preadmission CCB users and 387 nonusers by propensity score matching. Logistic regression analysis was then used to determine the association between preadmission CCB use and outcomes in pneumonia. Our study showed that the odds for development of severe sepsis was significantly lower in the CCB user group [odds ratio (OR), 0.466; 95% confidence interval (CI), 0.311-0.697; P = 0.002]. Preadmission CCB use was associated with a lower risk of contracting bacteremia (OR, 0.498; 95% CI, 0.262-0.99; P = 0.0327), lower risk of acute respiratory insufficiency (OR, 0.573; 95% CI, 0.412 0.798; P = 0.001), lower risk of intensive care unit admission (OR, 0.602; 95% CI, 0.432-0.840; P = 0.0028). In conclusion, our study suggested preadmission CCB use was associated with a reduction in the risks of development of respiratory insufficiency, bacteremia, and severe sepsis in patients admitted to the hospital with pneumonia. PMID- 26280293 TI - Operative Intervention of Supracondylar Humerus Fractures More Complicated in July: Analysis of the July Effect. AB - BACKGROUND: The "July Effect" involves the influx of new interns and residents early in the academic year (July and August), which may have greater potential for poorer patient outcomes. Current orthopaedic literature does not demonstrate the validity of this concept in arthroplasty, spine, hand, and arthroscopy. No study has investigated the possibility of this effect on common pediatric orthopaedic procedures, such as closed reduction and percutaneous pin fixation of supracondylar humerus fractures. METHODS: A retrospective review of all type II or III supracondylar humerus fractures that underwent primary closed reduction and percutaneous pin fixation (CPT code 24538) at a single pediatric level 1 trauma center from July 2009 to June 2013. Patients were grouped according to time in the academic year: early (July and August) and late (May and June). Demographic data included length of follow-up, age at surgery, sex, side of injury, and Wilkin's modified Gartland classification. Outcomes included length of operation, number of pins used, length of stay, complications, and the need for repeat surgery. RESULTS: There were 245 patients, 101 in the early and 144 in the late group. There was no increase in surgical time [33.32+/-24.74 (early) vs. 28.63+/-10.06 (late) min, P=0.07) or complication rates [7.0% (early) vs. 2.1% (late), P=0.06) between the early and the late groups. Cases performed with junior residents demonstrated longer operative (31.72+/-17.07 vs. 28.96+/-18.71 min, P=0.02) and fluoroscopy (48.63+/-30.96 vs. 34.12+/-27.38 s, P=0.01) times. CONCLUSIONS: The academic orthopaedic surgeon must ensure the education of residents, while providing the highest level of safety to patients. Our study shows that education of young residents early in the academic year results in no increase in operative times, radiation exposure, or complications. LEVEL OF EVIDENCE: Level III. PMID- 26280294 TI - The Fate of DDH Hips Showing Cartilaginous or Fibrous Tissue-filled Joint Spaces Following Primary Reduction. AB - BACKGROUND: Because the use of magnetic resonance imaging is still not universal for the patients with developmental dysplasia of the hip patients, orthopaedists do not generally distinguish widened joint spaces which are "empty" after primary treatment (and therefore still reducible), from those which are filled and much more difficult to treat. To date no studies have focused on the latter hips. We treated and observed the outcomes for 19 hips which showed filled joint spaces after primary treatment. METHODS: We retrospectively reviewed 19 cases of developmental dysplasia of the hip: (1) who showed a widened joint space on radiographs after primary treatment; and (2) whose magnetic resonance imaging showed that the widened joint space was accompanied by acetabular cartilage hypertrophy and/or was filled with fibrous tissues. All patients were over 1 year old at the time of primary reduction (reduction was closed in 4 patients, open in 6, and open with pelvic osteotomy in 9). Thirteen patients received at least 1 secondary treatment. Final results were classified using a modified Severin classification. RESULTS: Final outcomes were satisfactory in 10 (52.6%) and unsatisfactory in 9 (47.4%). The widened joint spaces gradually filled with bone, resulting in a shallow acetabulum in the patients with unsatisfactory results. Of 9 patients who underwent combined pelvic osteotomy at the time of primary reduction, results were satisfactory in 6 (66.7%), whereas all patients who had only closed or open primary reduction had unsatisfactory results. CONCLUSIONS: Combined pelvic osteotomy at the time of primary reduction is advisable in hips with widened joint spaces. However, hips with filled joint spaces after primary treatment often have unsatisfactory results even after additional pelvic and/or femoral osteotomy. LEVEL OF EVIDENCE: Level IV-prognostic study. PMID- 26280295 TI - The Use of an "Internal Fixator Technique" to Stabilize Pathologic Fractures Developing Secondary to Osteomyelitis. AB - BACKGROUND: There is no consensus on the materials and the techniques to use in fixing pathologic fractures secondary to osteomyelitis. This study reports the results of the fixation of pathologic fractures secondary to osteomyelitis using the "internal fixator technique." METHODS: The internal fixator technique was performed on 11 children and adolescents with fractures secondary to osteomyelitis between 2003 and 2010. A retrospective chart review was conducted to record the following: age, sex, the anatomic region of infection, the time delay from symptom onset to fracture, the classification of chronic osteomyelitis, the Cierny-Mader classification, the causative organism, surgeries, the length of hospitalization, the location and the pattern of fracture, the duration of infection, the length of follow-up, and complications. RESULTS: The patients included 7 male and 4 female patients with a mean age of 8.7 (range, 6 to 13) years. Pathologic fractures were as follows: 7 femur and 4 tibia. Nine of them were in the metaphysis and 2 others were located in the diaphysis. The time delay from symptom onset to fracture was 3.36 (1 to 9) months. The anatomic region of infection was the diaphysis in 2 cases and the metaphysis in 9 cases. Fractures patterns were short oblique and transverse. The length of hospitalization was a mean of 7 days. The duration of infection ranged from 1 to 12 (mean, 4.38) months. The mean duration of follow-up was 57.09 (range, 36 to 73) months from the initial presentation. Only 2 patients developed shortening, for which no additional intervention was performed. CONCLUSIONS: This case series demonstrates that the "internal fixator technique" is an acceptable alternative to the management of pathologic fractures of the femur or the tibia in children and adolescents with unresolved acute and chronic osteomyelitis. Infections were resolved in all cases and fractures were sufficiently stabilized to allow union with a low complication rate. LEVEL OF EVIDENCE: Level IV therapeutic. PMID- 26280296 TI - Predicting the Need for Surgical Intervention in Patients With Idiopathic Clubfoot. PMID- 26280297 TI - Thermal and cardiovascular strain imposed by motorcycle protective clothing under Australian summer conditions. AB - Motorcycle protective clothing can be uncomfortably hot during summer, and this experiment was designed to evaluate the physiological significance of that burden. Twelve males participated in four, 90-min trials (cycling 30 W) across three environments (25, 30, 35 degrees C [all 40% relative humidity]). Clothing was modified between full and minimal injury protection. Both ensembles were tested at 25 degrees C, with only the more protective ensemble investigated at 30 and 35 degrees C. At 35 degrees C, auditory canal temperature rose at 0.02 degrees C min(-1) (SD 0.005), deviating from all other trials (p < 0.05). The thresholds for moderate (>38.5 degrees C) and profound hyperthermia (>40.0 degrees C) were predicted to occur within 105 min (SD 20.6) and 180 min (SD 33.0), respectively. Profound hyperthermia might eventuate in ~10 h at 30 degrees C, but should not occur at 25 degrees C. These outcomes demonstrate a need to enhance the heat dissipation capabilities of motorcycle clothing designed for summer use in hot climates, but without compromising impact protection. Practitioner's Summary: Motorcycle protective clothing can be uncomfortably hot during summer. This experiment was designed to evaluate the physiological significance of this burden across climatic states. In the heat, moderate (>38.5 degrees C) and profound hyperthermia (>40.0 degrees C) were predicted to occur within 105 and 180 min, respectively. PMID- 26280299 TI - Distinct processing of social and monetary rewards in late adolescents with trait anhedonia. AB - OBJECTIVE: Anticipatory and consummatory dissociation of hedonic experience may manifest as trait anhedonia in healthy and clinical populations. It is still unclear whether the underlying neural mechanisms of the monetary-based and affect based incentive delay paradigms are distinct from each other. The present study aimed to examine the similarities and differences between the Affect Incentive Delay (AID) and the Monetary Incentive Delay (MID) imaging paradigms in relation to brain activations. METHOD: We administered the AID and the MID imaging tasks to 28 adolescent participants. A cue signaling the type of forthcoming feedback (reward or punishment) was displayed to the participants, followed by a target hit task with corresponding reward or punishment. RESULTS: The striatal and limbic regions were activated during the anticipatory phase of MID, while there was no brain activation during the anticipatory phase of AID. In the consummatory phase, the MID task activated the medial frontal cortex, while the AID task activated the frontal and dorsal limbic regions. We further found that the anhedonic group exhibited significant hypoactivation than the nonanhedonic group at the left pulvinar, the left claustrum and the left insula to positive cues in the anticipatory phase of the AID task. CONCLUSIONS: The results suggest that the AID and the MID tasks have unique activation patterns. Our findings also suggest that the AID task may be more sensitive in detecting anhedonia in people with trait anhedonia. PMID- 26280298 TI - Reduced immune responses in chimeric mice engrafted with bone marrow cells from mice with airways inflammation. AB - OBJECTIVE: During respiratory inflammation, it is generally assumed that dendritic cells differentiating from the bone marrow are immunogenic rather than immunoregulatory. Using chimeric mice, the outcomes of airways inflammation on bone marrow progenitor cells were studied. METHODS: Immune responses were analyzed in chimeric mice engrafted for >16 weeks with bone marrow cells from mice with experimental allergic airways disease (EAAD). RESULTS: Responses to sensitization and challenge with the allergen causing inflammation in the bone marrow-donor mice were significantly reduced in the chimeric mice engrafted with bone marrow cells from mice with EAAD (EAAD-chimeric). Responses to intranasal LPS and topical fluorescein isothiocyanate (non-specific challenges) were significantly attenuated. Fewer activated dendritic cells from the airways and skin of the EAAD-chimeric mice could be tracked to the draining lymph nodes, and may contribute to the significantly reduced antigen/chemical-induced hypertrophy in the draining nodes, and the reduced immune responses to sensitizing allergens. Dendritic cells differentiating in vitro from the bone marrow of >16 weeks reconstituted EAAD-chimeric mice retained an ability to poorly prime immune responses when transferred into naive mice. CONCLUSIONS: Dendritic cells developing from bone marrow progenitors during airways inflammation are altered such that daughter cells have reduced antigen priming capabilities. PMID- 26280300 TI - Executive functions and the contribution of short-term memory span in children with specific language impairment. AB - OBJECTIVE: An increasing number of results show that specific language impairment (SLI) is often associated with impairments in executive functions (EF), but the nature, extent, and generality of these deficits is yet unclear. The aim of the paper is to present results from verbal and nonverbal tasks examining EF in children with SLI and their age-matched typically developing (TD) peers. METHOD: 31 children with SLI were tested on verbal and nonverbal versions of simple and complex span, fluency, N-back, and Stroop tasks. Their performance was compared with 31 TD children matched on age and nonverbal IQ. The design allows us to examine whether executive functions are similarly affected in SLI in verbal and nonverbal tasks. RESULTS: The SLI group showed difficulties in verbal versions of complex span (listening span task) and fluency but not in inhibition (Stroop tasks) relative to TD age-matched children. Including simple verbal span (digit span) as a covariate eliminated group differences on both verbal tasks. CONCLUSIONS: Children with SLI were found to be impaired on several verbal measures of EF, but these differences were largely due to more fundamental deficits in verbal short-term span. PMID- 26280301 TI - Distinguishing Alzheimer's disease and dementia with Lewy bodies using cognitive and olfactory measures. AB - OBJECTIVE: Given poor sensitivity of the diagnostic criteria in identifying dementia with Lewy bodies (DLB), the use of cognitive and olfactory measures to distinguish Alzheimer's disease (AD) from DLB was assessed. METHOD: Twenty-six patients with DLB and 60 patients with AD were administered several cognitive measures and the Brief Smell Identification Task (BSIT). RESULT: Patients with DLB performed significantly worse on the BSIT and visuoconstruction tasks than patients with AD, but significantly better on delayed recall of a word list. Sensitivity and specificity of these measures in identifying DLB are presented for each of these tasks alone and in combination. The best balance of sensitivity and specificity was found with a combination of the Hopkins Verbal Learning Test and BSIT (81% sensitivity, 90% specificity). CONCLUSIONS: These data have practical implications by providing cut scores than can be used to emphasize either specificity or sensitivity in identifying patients with DLB. PMID- 26280302 TI - Inhibition of Cancer-Associated Mutant Isocitrate Dehydrogenases by 2 Thiohydantoin Compounds. AB - Somatic mutations of isocitrate dehydrogenase 1 (IDH1) at R132 are frequently found in certain cancers such as glioma. With losing the activity of wild-type IDH1, the R132H and R132C mutant proteins can reduce alpha-ketoglutaric acid (alpha-KG) to d-2-hydroxyglutaric acid (D2HG). The resulting high concentration of D2HG inhibits many alpha-KG-dependent dioxygenases, including histone demethylases, to cause broad histone hypermethylation. These aberrant epigenetic changes are responsible for the initiation of these cancers. We report the synthesis, structure-activity relationships, enzyme kinetics, and binding thermodynamics of a novel series of 2-thiohydantoin and related compounds, among which several compounds are potent inhibitors of mutant IDH1 with Ki as low as 420 nM. X-ray crystal structures of IDH1(R132H) in complex with two inhibitors are reported, showing their inhibitor-protein interactions. These compounds can decrease the cellular concentration of D2HG, reduce the levels of histone methylation, and suppress the proliferation of stem-like cancer cells in BT142 glioma with IDH1 R132H mutation. PMID- 26280303 TI - Validating psychological classification criteria in the context of somatoform disorders: A one- and four-year follow-up. AB - When revising the former somatoform diagnoses to somatic symptom disorders, DSM-5 introduced psychological classification criteria in addition to somatic symptoms. The authors investigated the relevance of these and further cognitive, affective, and behavioral features as well as their predictive value concerning (a) somatic symptoms that are not better explained by a general medical condition (MUS) and somatoform disorders (SD), (b) impairment, and (c) health care utilization. A general population sample of 321 participants (M = 47.0 years, 63% women) was interviewed at baseline and reinterviewed 1 year (N = 244) and 4 years (N = 219) later. The authors assessed a list of 49 somatic complaints including medical causes, the symptom-related subjective impairment, doctor visits during the previous 12 months, depressive/anxiety disorders (SCID), and 9 psychological features with potential use for classification. Most psychological features were more frequent in subjects with SD compared to nonsufferers. Reassurance seeking, body checking, a self-concept of bodily weakness, catastrophizing of physical sensations, avoidance of physical activities, and negative affectivity incrementally predicted medium- and long-term standard deviation: The odds ranged from 2.4 to 9.8 (95% confidence intevals: [1.1, 5.0], [1.7-57.9]), with up to 90% correct predictions for the overall model. Lower somatic symptom attribution and higher health anxiety were incremental predictors of the number of MUS after 4 years. Long-term impairment and health care use were not incrementally predicted by psychological features. To conclude, psychological criteria showed relevance and predictive value for the classification of somatoform symptoms. Therefore, the inclusion seems warranted, although the DSM-5 selection of psychological features needs further investigation. PMID- 26280304 TI - Unique Optical Oxygen-Sensing Performance of [Ru(IP)2(HNAIP)](2+) during the Groove-Binding-Induced B-to-Z DNA Conformational Transition. AB - The oxygen-sensing performance of [Ru(IP)2(HNAIP)](2+) (Ru1, IP = imidazo[4,5 f][1,10]phenanthroline and HNAIP = 2-(2-hydroxy-1-naphthyl)imidazo [4,5 f][1,10]phenanthroline) in the presence of DNA conformational transition has been investigated by means of absorption spectroscopy, steady-state and time-resolved fluorescence spectroscopies, and circular dichroism spectroscopy. Ru1 shows a good linear response toward oxygen between pure nitrogen and pure oxygen with an on-off emission intensity ratio (I0/I100) of up to 9.3 via a dynamic quenching mechanism. Compared with [Ru(IP)2(DHPIP)](2+) (Ru2, DHPIP = 2-(2,4 dihydroxyphenyl)imidazo[4,5-f][1,10]phenanthroline, I0/I100 = 5.8), the HNAIP ligand endows Ru1 with favorable oxygen binding sites to achieve larger energy and electron transfer rates. Simultaneously, Ru1 can induce the B-to-Z DNA conformational transition via a groove interaction with an intrinsic binding constant (K(b)) of 7.9 * 10(4) M(-1), whereas there is no same phenomenon for Ru2 intercalated into DNA (Kb = 3.3 * 10(5) M(-1)). Furthermore, the B-to-Z DNA conformational transition is interestingly found to decrease the Ru1-based oxygen sensing rate by about 33%. PMID- 26280305 TI - Broadband High-Performance Infrared Antireflection Nanowires Facilely Grown on Ultrafast Laser Structured Cu Surface. AB - Infrared antireflection is an essential issue in many fields such as thermal imaging, sensors, thermoelectrics, and stealth. However, a limited antireflection capability, narrow effective band, and complexity as well as high cost in implementation represent the main unconquered problems, especially on metal surfaces. By introducing precursor micro/nano structures via ultrafast laser beforehand, we present a novel approach for facile and uniform growth of high quality oxide semiconductor nanowires on a Cu surface via thermal oxidation. Through the enhanced optical phonon dissipation of the nanowires, assisted by light trapping in the micro structures, ultralow total reflectance of 0.6% is achieved at the infrared wavelength around 17 MUm and keeps steadily below 3% over a broad band of 14-18 MUm. The precursor structures and the nanowires can be flexibly tuned by controlling the laser processing procedure to achieve desired antireflection performance. The presented approach possesses the advantages of material simplicity, structure reconfigurability, and cost-effectiveness for mass production. It opens a new path to realize unique functions by integrating semiconductor nanowires onto metal surface structures. PMID- 26280306 TI - Introduction to the Special Issue. Festschrift for Hannelore Wass, Founding Editor of Death Studies. PMID- 26280307 TI - The long-term variation of Cd and Zn hyperaccumulation by Noccaea spp and Arabidopsis halleri plants in both pot and field conditions. AB - Three Cd and Zn hyperaccumulating plant species Noccaea caerulescens Noccaea praecox and Arabidopsis halleri (Brassicacceae) were cultivated in seven subsequent vegetation seasons in both pot and field conditions in soil highly contaminated with Cd, Pb, and Zn. The results confirmed the hyperaccumulation ability of both plant species, although A. halleri showed lower Cd uptake compared to N. caerulescens. Conversely, Pb phytoextraction was negligible for both species in this case. Because of the high variability in plant yield and element contents in the aboveground biomass of plants, great variation in Cd and Zn accumulation was observed during the experiment. The extraction ability in field conditions varied in the case of Cd from 0.2 to 2.9 kg ha(-1) (N. caerulescens) and up to 0.15 kg ha(-1) (A. halleri), and in the case of Zn from 0.2 to 6.4 kg ha(-1) (N. caerulescens) and up to 13.8 kg.ha(-1) (A. halleri). Taking into account the 20 cm root zone of the soil, the plants were able to extract up to 4.1% Cd and 0.2% Zn in one season. However, cropping measures should be optimized to improve and stabilize the long-term phytoextraction potential of these plants. PMID- 26280309 TI - A new approach to the 8b-azaacenaphthylene ring system. AB - A stereoselective approach to the 8b-azaacenaphthylene ring system is described. This new route features a dichloroketene-enol ether [2 + 2] cycloaddition, a vinylogous Mannich reaction, and an aza-Prins cyclization as key stereoselective transformations. PMID- 26280308 TI - Improved age determination of blood and teeth samples using a selected set of DNA methylation markers. AB - Age estimation from DNA methylation markers has seen an exponential growth of interest, not in the least from forensic scientists. The current published assays, however, can still be improved by lowering the number of markers in the assay and by providing more accurate models to predict chronological age. From the published literature we selected 4 age-associated genes (ASPA, PDE4C, ELOVL2, and EDARADD) and determined CpG methylation levels from 206 blood samples of both deceased and living individuals (age range: 0-91 years). This data was subsequently used to compare prediction accuracy with both linear and non-linear regression models. A quadratic regression model in which the methylation levels of ELOVL2 were squared showed the highest accuracy with a Mean Absolute Deviation (MAD) between chronological age and predicted age of 3.75 years and an adjusted R(2) of 0.95. No difference in accuracy was observed for samples obtained either from living and deceased individuals or between the 2 genders. In addition, 29 teeth from different individuals (age range: 19-70 years) were analyzed using the same set of markers resulting in a MAD of 4.86 years and an adjusted R(2) of 0.74. Cross validation of the results obtained from blood samples demonstrated the robustness and reproducibility of the assay. In conclusion, the set of 4 CpG DNA methylation markers is capable of producing highly accurate age predictions for blood samples from deceased and living individuals. PMID- 26280310 TI - The Kra Isthmus Canal: A New Strategic Solution for China's Energy Consumption Scenario? AB - This paper is a conceptual study that examines the viability of the construction of the Kra Isthmus within the context of the five dimensions of megaproject success of Sovacool and Cooper (The governance of energy megaprojects: politics, hubris, and energy security, 2013)-social (governance), technological (systems), democratic (politics), externalities (economics, ecology), and risks assessments (accountability), and its possible impact on China's strategic energy supply chain. One of the objectives of this study is also to discuss the current impacts, perceived benefits, and risks of China's dependence on its multinational and transnational pipelines. China could see the construction of Kra Canal as an alternative option for its strategic sourcing activities especially crude oil and gas at much lower costs. The megaproject would become a passageway that connects the Indian Ocean, Andaman Sea, and the Gulf of Siam at the choke point of Isthmus region in Thailand. However, this megaproject could also trigger the internal conflicts of Thailand, and affect the ASEAN countries' political and economic relationships. PMID- 26280311 TI - Does Place Attachment Predict Wildfire Mitigation and Preparedness? A Comparison of Wildland-Urban Interface and Rural Communities. AB - Wildfires are a common occurrence in many countries and are predicted to increase as we experience the effects of climate change. As more people are expected to be affected by fires, it is important to increase people's wildfire mitigation and preparation. Place attachment has been theorized to be related to mitigation and preparation. The present study examined place attachment and wildfire mitigation and preparation in two Australian samples, one rural and one on the wildland urban interface. The study consisted of 300 participants who responded to questionnaires about their place attachment to their homes and local areas, as well as describing their socio-demographic characteristics and wildfire mitigation and preparedness. Hierarchical regression showed that place attachment to homes predicted wildfire mitigation and preparedness in the rural sample but not in the wildland-urban interface sample. The results suggest that place attachment is a motivator for mitigation and preparation only for people living rurally. Reminding rural residents of their attachment to home at the beginning of wildfire season may result in greater mitigation and preparedness. Further research focusing on why attachment does not predict mitigation and preparedness in the wildland-urban interface is needed. PMID- 26280312 TI - Scaling properties of the shear modulus of polyelectrolyte complex coacervates: a time-pH superposition principle. AB - We analyze the scaling properties of pH-dependent shear modulus spectra of complex coacervates made of weak polyanions and strong polycations. For the first time, we report on a "time-pH superposition principle". This principle implies that the charge density in complex coacervates made of not fully charged polyions only influences the time scale of the relaxation dynamics, but not the mechanisms of the underlying dynamics. PMID- 26280313 TI - "Unfocus" on foc.us: commercial tDCS headset impairs working memory. AB - In this study, we tested whether the commercial transcranial direct current stimulation (tDCS) headset foc.us improves cognitive performance, as advertised in the media. A single-blind, sham-controlled, within-subject design was used to assess the effect of online and off-line foc.us tDCS-applied over the prefrontal cortex in healthy young volunteers (n = 24) on working memory (WM) updating and monitoring. WM updating and monitoring, as assessed by means of the N-back task, is a cognitive-control process that has been shown to benefit from interventions with CE-certified tDCS devices. For both online and off-line stimulation protocols, results showed that active stimulation with foc.us, compared to sham stimulation, significantly decreased accuracy performance in a well-established task tapping WM updating and monitoring. These results provide evidence for the important role of the scientific community in validating and testing far-reaching claims made by the brain training industry. PMID- 26280314 TI - Temporal and spatial constraints of action effect on sensory binding. AB - Previous studies have shown that asynchrony in perceived changes in the visual attributes of an object is attenuated when the object is the target of a manual reaching action (e.g. Corveleyn et al. in J Vis, 2012. doi: 10.1167/12.11.20 ). In the present study, we examined the temporal and spatial constraints associated with the effect of action on sensory binding. Participants performed a temporal order judgment task which required them to judge which changed first, the position or the colour of a visual stimulus, either while performing a concurrent motor task (manual acquisition of a visual target) or not (perceptual task). In Experiment 1, the fixed-attribute change (colour or position) occurred 0, 250, 500 or 1000 ms following the end of the motor action or the presentation of an auditory cue, while the variable-attribute change (position or colour) occurred randomly within an interval of +/-200 ms from the fixed-attribute change. In Experiment 2, the visual stimulus was presented at a distance of 0, 2, 4 or 8 cm from a central fixation cross which was the target in the motor task. The fixed attribute (colour or position) changed 700 ms after an auditory cue (perceptual task) or when the hand reached the visual target (motor task). The variable attribute change (position or colour) again occurred within an interval of +/-200 ms from the fixed-attribute change. Statistical analysis of the point of subjective simultaneity revealed that performing a motor action reduced the perceived temporal asynchrony in the perceptual task, but only when the visual changes occurred less than 500 ms (for the fixed attribute) following movement execution (Exp. 1) and at a distance of less than 4 cm from the movement endpoint (Exp. 2). These results indicate that action-induced sensory binding requires temporal contiguity and spatial congruency between the endpoint of the action and its visual consequences. PMID- 26280315 TI - Relative errors can cue absolute visuomotor mappings. AB - When repeatedly switching between two visuomotor mappings, e.g. in a reaching or pointing task, adaptation tends to speed up over time. That is, when the error in the feedback corresponds to a mapping switch, fast adaptation occurs. Yet, what is learned, the relative error or the absolute mappings? When switching between mappings, errors with a size corresponding to the relative difference between the mappings will occur more often than other large errors. Thus, we could learn to correct more for errors with this familiar size (Error Learning). On the other hand, it has been shown that the human visuomotor system can store several absolute visuomotor mappings (Mapping Learning) and can use associated contextual cues to retrieve them. Thus, when contextual information is present, no error feedback is needed to switch between mappings. Using a rapid pointing task, we investigated how these two types of learning may each contribute when repeatedly switching between mappings in the absence of task-irrelevant contextual cues. After training, we examined how participants changed their behaviour when a single error probe indicated either the often-experienced error (Error Learning) or one of the previously experienced absolute mappings (Mapping Learning). Results were consistent with Mapping Learning despite the relative nature of the error information in the feedback. This shows that errors in the feedback can have a double role in visuomotor behaviour: they drive the general adaptation process by making corrections possible on subsequent movements, as well as serve as contextual cues that can signal a learned absolute mapping. PMID- 26280316 TI - Comparison and preparation of multilayered polylactic acid fabric strengthen calcium phosphate-based bone substitutes for orthopedic applications. AB - An attempt to maintain the three-dimensional space into restorative sites through the conveniently pack porous fillers are general used strategy. Advancement in the manufacturing protective shells in the scaffolds, which would be filled with brittle ceramic grafts for the development of highly connective pores provides the approach to solve crack problem for generating the tissues. Therefore, multilayered braided and alkalized poly(lactic acid) (PLA) composites with calcium phosphate bone cement (CPC) were synthesized and compared. The PLA/CPC composites were divided into various groups according to a series of heat treatment temperatures (100-190 degrees C) and periods (1-3 h) and then characterized. The effects of 24-h immersion on the strength decay resistance of the samples were compared. Results showed that the residual oil capped on the surfaces of alkalized PLA braid was removed, and the structure was unaltered. However, the reduced tensile stress of alkalized PLA braids was due to ester group formation by hydrolysis. Mechanical test results of PLA/CPC composites showed that the strength significantly increased after heat treatment, except when the heating temperature was higher than the PLA melting point at approximately 160-170 degrees C. The degree of PLA after recrystallization became higher than that of unheated composites, thereby leading to reduced strength and toughness of the specimen. Braiding fibers of biodegradable PLA reinforced and toughened the structure particularly of the extra-brittle material of thin-sheet CPC after implantation. PMID- 26280317 TI - Adaptive correlation dimension method for analysing heart rate variability during the menstrual cycle. AB - Correlation dimension (CD) is used for analysing the chaotic behaviour of the nonlinear heart rate variability (HRV) time series. In CD, the autocorrelation function is used to calculate the time delay. However, it does not provide optimum values of time delays, which leads to an inaccurate estimation of the HRV between phases of the menstrual cycle. Thus, an adaptive CD method is presented here to calculate the optimum value of the time delay based upon the information content in the HRV signal. In the proposed method, the first step is to divide the HRV signal into overlapping windows. Afterwards, the time delay is calculated for each window based on the features of the signal. This procedure of finding the optimum time delay for each window is known as adaptive autocorrelation. Then, the CD for each window is calculated using optimum time delays. Finally, adaptive CD is calculated by averaging the CD of all windows. The proposed method is applied on two data sets: (i) the standard Physionet dataset and (ii) the dataset acquired using BIOPAC((r))MP150. The results show that the proposed method can accurately differentiate between normal and diseased subjects. Further, the results prove that the proposed method is more accurate in detecting HRV variations during the menstrual cycles of 74 young women in lying and standing postures. Three statistical parameters are used to find the effectiveness of adaptive autocorrelation in calculating time delays. The comparative analysis validates the superiority of the proposed method over detrended fluctuation analyses and conventional CD. PMID- 26280319 TI - The correlation of resistance exercise-induced myostatin with insulin resistance and plasma cytokines in healthy young men. AB - PURPOSE: This study was designed to examine the correlation of resistance exercise (RE)-induced myostatin (MSTN) with insulin resistance and plasma cytokines in healthy young men. METHODS: Twenty-four healthy men were randomly divided into RE (n = 12) and control (n = 12) group. After a session of familiarization, one repetition maximum (1-RM) was calculated. Circuit RE program involved 3 sets of 15 repetitions at 55 % of 1-RM. Blood samples were collected before and 24 h after the exercise. Paired t test, independent t test, and Pearson's correlation were used for analyzing data. RESULTS: A significant decrease in plasma level of MSTN, glucose, insulin, interleukin-6 (IL-6), and homeostasis model assessment of insulin resistance (HOMA-IR) and a significant increase in plasma interleukin-10 (IL-10) were found in RE group 24 h post exercise versus pre-exercise (p < 0.05). Furthermore, except plasma IL-10, a significant decrease in metabolic variables was found in RE group versus control group (p < 0.05). A significantly positive correlation of plasma MSTN with HOMA IR and plasma IL-6 and a significantly negative correlation of plasma MSTN with plasma IL-10 were found in RE group versus control group (p < 0.05). CONCLUSIONS: It seems that a circuit RE bout by reducing HOMA-IR and changing plasma cytokines (decreased IL-6 and increased IL-10) can decrease plasma level of MSTN in healthy young men. In other word, the beneficial effect of acute RE may be reflected by changes in MSTN in healthy young individuals. PMID- 26280318 TI - Improving the diagnosis of 11beta-hydroxylase deficiency using home-made MLPA probes: identification of a novel chimeric CYP11B2/CYP11B1 gene in a Sicilian patient. AB - PURPOSE: 11beta-Hydroxylase deficiency (11OHD) represents the second most common cause of congenital adrenal hyperplasia. It is caused by mutations in the CYP11B1 gene localized about 40 kb from the CYP11B2 gene with which it shares a homology of 95 %. The asymmetric recombination of these two genes is involved both in 11OHD and in glucocorticoid-remediable aldosteronism (GRA). Our objective was to set up an easy and rapid method to detect these hybrid genes and other kinds of deletions, to improve the molecular diagnosis of 11OHD. METHODS: A set of 8 specific probes for both the CYP11B1 and the CYP11B2 genes to be used for multiplex ligation-dependent probe amplification (MLPA) analysis was designed to detect rearrangements of these genes. RESULTS: The method developed was tested on 15 healthy controls and was proved to be specific and reliable; it led us to identify a novel chimeric CYP11B2/CYP11B1 gene in one patient that carried the known A306V mutation on the other allele. Specific amplification and sequencing of the hybrid gene confirmed the breakpoint localization in the second intron. CONCLUSIONS: The MLPA kit developed enables the detection of deletions, duplications or chimeric genes and represents an optimal supplement to DNA sequence analysis in patients with 11OHD. In addition, it can also be used to show the presence of the opposite chimaera associated with GRA. PMID- 26280320 TI - Comparison of histopathological features and prognosis of classical and follicular variant papillary thyroid carcinoma. AB - PURPOSE: To compare the histopathological features and the outcomes of the follicular variant and classical variant of papillary thyroid carcinoma. MATERIAL AND THE METHODS: Demographic data, histopathological features (tumor size, thyroid capsule invasion, extrathyroidal extension, vascular invasion and multicentricity), lymph node metastasis, local recurrence, distant metastasis and mortality during the follow-up of 258 C-PTC and 153 FVPTC patients who underwent total thyroidectomy were compared. The dynamic risk assessment system was used to refine postoperative risk estimates based on the assessment of response to initial treatment. RESULTS: The demographic data showed no significant difference between the two groups. The mean tumor size showed no significant difference between the two groups. The rate of thyroid capsule invasion, extrathyroidal extension, and lymph node metastasis was significantly higher in C-PTC than in FVPTC group, whereas multicentricity and bilobar involvement were significantly higher in FVPTC group than in C-PTC group. Central lymph node metastasis was significantly more frequent in patients with C-PTC than in those with FVPTC (p < 0.0001). Local recurrence was found in 22 (5.3 %) patients overall and was significantly more common in C-PTC group than in FVPTC group. In patients >=45 years, the local recurrence rate was significantly higher in patients with CPTC than in those with FVPTC. The local recurrence rate in patients <45 years was not significantly different between the two groups of patients. The multicentricity rate was significantly higher in the FVPTC group for both age groups. Dynamic risk assessment showed that the rate of intermediate- and high-risk groups showed no significant difference between C-PTC and FVPTC patients but the rate of low risk patients was higher in FVPTC group than in C-PTC group (p = 0.04). The recurrence rate in low-risk group was found higher in C-PTC compared to FVPTC patients (4.7 vs. 0.7 %, p = 0.04, respectively). The recurrence rate showed no significant difference in both intermediate- and high-risk groups in C-PTC and FVPTC patients. During the follow-up, the rate of distant metastasis and disease specific mortality was not significantly different between the two groups (p = 0.25). CONCLUSION: FVPTC is a common subtype of PTC and has a higher rate of multicentricity with bilobar involvement. Although aggressive histopathologic features, such as thyroid capsule invasion, extrathyroidal extension, and lymph node metastasis, are significantly more frequent in CPTC than in FVPTC, the long term outcome is similar in both subtypes after appropriate initial surgery and postoperative RAI ablation treatment. PMID- 26280322 TI - Key Agreement Schemes in Wireless Body Area Networks: Taxonomy and State-of-the Art. AB - Advances in wearable and implantable biosensors have enabled the applicability and usability of wireless body area networks (WBANs). A WBAN allows biosensors to collect and communicate human physiological data using wireless communication. The communication security of the collected data in WBAN is a major concern. Because of the dependability of cryptographic schemes for key management, these have become an important aspect of this security. However, the extremely constrained nature of biosensors has made designing key management schemes a challenging task. For this reason, many lightweight key management schemes have been proposed to overcome these constraints. In this article, we present a review of the state of the art of these solutions. We classify the WBAN schemes into three classes and evaluate them based on adequate metrics for key management in WBAN. PMID- 26280321 TI - The impact of the presence of antithyroid antibodies on pregnancy outcome following intracytoplasmatic sperm injection-ICSI and embryo transfer in women with normal thyreotropine levels. AB - PURPOSE: The aim of our study was to investigate the impact of anti-thyroid peroxidase antibodies (Anti-TPO) on pregnancy outcome following the in vitro fertilization and embryo transfer (IVF-ET) in general groups and in subgroups divided according to AMH level and age. METHODS: A total of 114 patients positive for anti-thyroid peroxidase antibodies (Anti-TPO+ group) and 495 infertile women negative for anti-thyroid peroxidase antibodies (Anti-TPO- group) undergoing IVF with ICSI from April 2010 to April 2012 were analyzed retrospectively. RESULTS: There were no significant differences in age, BMI, basal FSH, LH, AMH levels and duration of infertility between the two main groups. No significant differences in terms of the days of ovarian stimulation, estradiol level in day 8, total gonadotropin dose, number of oocytes retrieved, available embryos and blastocysts, number of embryos transferred nor in rates of fertilization, implantation, clinical pregnancy, live birth and abortion rate between two main groups were found. The only statistically significant difference among the groups with different anti-TPO antibodies levels was found in basal FSH concentration and BMI. Among the clinical outcomes of IVF with respect to the different anti TPO levels, the only significant difference was found for the number of oocytes retrieved. Analysis of the baseline parameters in relationship to age categories and AMH levels found significant differences between women positive and negative for thyroid antibodies with respect to basal FSH and LH levels for women >37 years and for basal FSH in AMH <0.6 subgroup. CONCLUSIONS: The present study reveals that patients with anti-TPO antibodies showed no significant differences in fertilization, implantation, pregnancy rates, live birth rates and no higher risk for miscarriage following IVF-ET when compared with those negative for anti thyroid antibodies. PMID- 26280323 TI - Informativeness of minisatellite and microsatellite markers for genetic analysis in papaya. AB - The objective of this study was to evaluate information on minisatellite and microsatellite markers in papaya (Carica papaya L.). Forty minisatellites and 91 microsatellites were used for genotyping 24 papaya accessions. Estimates of genetic diversity, genetic linkage and analyses of population structure were compared. A lower average number of alleles per locus was observed in minisatellites (3.10) compared with microsatellites (3.57), although the minisatellites showed rarer alleles (18.54 %) compared with microsatellite (13.85 %). Greater expected (He = 0.52) and observed (Ho = 0.16) heterozygosity was observed in the microsatellites compared with minisatellites (He = 0.42 and Ho = 0.11), possibly due to the high number of hermaphroditic accessions, resulting in high rates of self-fertilization. The polymorphic information content and Shannon Wiener diversity were also higher for microsatellites (from 0.47 to 1.10, respectively) compared with minisatellite (0.38 and 0.85, respectively). The probability of paternity exclusion was high for both markers (>0.999), and the combined probability of identity was from 1.65(-13) to 4.33(-38) for mini- and micro-satellites, respectively, which indicates that both types of markers are ideal for genetic analysis. The Bayesian analysis indicated the formation of two groups (K = 2) for both markers, although the minisatellites indicated a substructure (K = 4). A greater number of accessions with a low probability of assignment to specific groups were observed for microsatellites. Collectively, the results indicated higher informativeness of microsatellites. However, the lower informative power of minisatellites may be offset by the use of larger number of loci. Furthermore, minisatellites are subject to less error in genotyping because there is greater power to detect genotyping systems when larger motifs are used. PMID- 26280324 TI - Cloning and Overexpression of the als, pflA, and adhB Genes in Streptococcus thermophilus and Their Effects on Metabolite Formation. AB - Streptococcus thermophilus is a lactic acid bacterium and used as starter culture in the dairy industry, mainly in the manufacture of yoghurt, with Lactobacillus delbrueckii subsp. bulgaricus. It produces lactic acid as a major fermentation end product and some carbonyl compounds through sugar metabolism. The level of metabolites could be improved using molecular biotechnology. The genes of als, encoding alpha-acetolactate synthase (Als), the pflA, encoding pyruvate-formate lyase activating enzyme (PflA), and the adhB which encodes alcohol dehydrogenase (AdhB) of S. thermophilus NCFB2393 strain were amplified by polymerase chain reaction and separately cloned into the overexpression vector pNZ276 under the control of the lacA promoter. The strains were transformed individually with the constructed plasmids. Their abilities to generate important metabolites such as pyruvate, lactate, formate, acetaldehyde, acetoin, ethanol, and 2,3-butanediol in LM17 medium were analyzed using high-performance liquid chromatography. High level of 2,3-butanediol was obtained by overexpressing the als gene. The level of formate increased slightly by overexpressing the pflA gene. The overexpression of the adhB gene, on the other hand, resulted in a significant increase in the ethanol level. PMID- 26280325 TI - Prevalence of microorganisms co-infections in human papillomaviruses infected women in Northern China. AB - PURPOSE: Due to scarce data on the prevalence of genital microorganism infections among individuals with human papillomavirus (HPV) infections, the present study aimed to evaluate microorganism co-infections and associated risk factors in HPV infected women in Northern China. METHODS: Cervical samples of 4290 enrolled female patients were collected to detect HPV, bacterial and yeast infections in gynecologic outpatients. Serum samples collected were analyzed for the presence of serological markers for human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV) and Treponema pallidum infections. HPV typing was carried out by polymerase chain reaction and flow-through hybridization on cervical brush specimens. Chlamydia trachomatis was identified by strand displacement amplification, and other microorganisms were detected by conventional methods. Odds ratio of co-infection was assessed between HPV-positive and -negative patients. RESULTS: Overall, co-infections among HPV-infected patients showed a trend for risk compared with HPV-negative patients. In this cross-sectional study on 4290 female outpatients, statistical analyses revealed a significant association between HPV and detection of anti-HBV antibodies, bacterial vaginosis, C. trachomatis and Ureaplasma urealyticum; no correlation was found between HPV infection and anti-HIV, anti-HCV, T. pallidum, Trichomonas vaginalis and Neisseria gonorrhoeae, which were detected only in few cases among either HPV positive or -negative patients. CONCLUSION: The study demonstrated a significant association between HPV and HBV, bacterial vaginosis, C. trachomatis and U. urealyticum. The study results suggest that it may be important to screen for the simultaneous presence of different microorganism co-infections with HPV that may have synergistic pathological effects. PMID- 26280326 TI - Assessment of uterine enhancement rate after abdominal radical trachelectomy using dynamic contrast-enhanced magnetic resonance imaging. AB - PURPOSE: The purpose of this study was to assess uterine enhancement rate after abdominal radical trachelectomy (ART) using dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging. METHODS: Ten patients with early uterine cervical cancer, who were treated by ART, were included in this study. Each patient underwent DCE MR imaging using a 3 T unit to assess uterine enhancement rate at three times (before surgery and 1 and 3 months after surgery). The radiologist calculated mean signal intensities of the anterior and posterior myometrium and also measured the signal intensities of the urine in the bladder on the same image, which was expressed as the myometrium-to-urine signal intensity ratio. In the time-intensity ratio curve, enhancement parameters (peak signal intensity ratio and peak time) of the uterine body were compared across the three MR examinations. RESULTS: The peak signal intensity ratio was 6.96 +/- 0.98 on MR examinations before surgery, 6.14 +/- 0.81 1 month after surgery, and 6.26 +/- 0.63 3 months after surgery (p = 0.069). The peak time was 57.6 +/- 3.4 s on MR examinations before surgery, 56.4 +/- 4.4 s 1 month after surgery, and 53.2 +/- 8.0 s 3 months after surgery (p = 0.304). No significant differences were found in either the peak signal intensity ratio or peak time across the three MR examinations. CONCLUSIONS: That no significant decrease of uterine enhancement rate was found after surgery suggests the uterine function and fertility may be preserved after ART. PMID- 26280327 TI - Thoughts in space: the impact of environmental surround on cognitive processing. AB - The embodied cognition perspective has provided a formalization of the idea that the motor state is a characteristic of being that permeates all of human processing. We review this perspective and experimental evidence supporting its claim. It is further considered that the motor behaving human moves within various spaces, each affording different actions. To this end, it is proposed that the environmental surround is a critical variable in the embodied cognition perspective. Thoughts, inasmuch as they may be grounded in simulation of motor behavioural responses, require time but also space. We suggest that these time space considerations occur within a proposed concept of the potentiated state. PMID- 26280328 TI - EMRinger: side chain-directed model and map validation for 3D cryo-electron microscopy. AB - Advances in high-resolution cryo-electron microscopy (cryo-EM) require the development of validation metrics to independently assess map quality and model geometry. We report EMRinger, a tool that assesses the precise fitting of an atomic model into the map during refinement and shows how radiation damage alters scattering from negatively charged amino acids. EMRinger (https://github.com/fraser-lab/EMRinger) will be useful for monitoring progress in resolving and modeling high-resolution features in cryo-EM. PMID- 26280329 TI - Ultrahigh-throughput single-molecule spectroscopy and spectrally resolved super resolution microscopy. AB - By developing a wide-field scheme for spectral measurement and implementing photoswitching, we synchronously obtained the fluorescence spectra and positions of ~10(6) single molecules in labeled cells in minutes, which consequently enabled spectrally resolved, 'true-color' super-resolution microscopy. The method, called spectrally resolved stochastic optical reconstruction microscopy (SR-STORM), achieved cross-talk-free three-dimensional (3D) imaging for four dyes 10 nm apart in emission spectrum. Excellent resolution was obtained for every channel, and 3D localizations of all molecules were automatically aligned within one imaging path. PMID- 26280330 TI - Wirelessly powered, fully internal optogenetics for brain, spinal and peripheral circuits in mice. AB - To enable sophisticated optogenetic manipulation of neural circuits throughout the nervous system with limited disruption of animal behavior, light-delivery systems beyond fiber optic tethering and large, head-mounted wireless receivers are desirable. We report the development of an easy-to-construct, implantable wireless optogenetic device. Our smallest version (20 mg, 10 mm(3)) is two orders of magnitude smaller than previously reported wireless optogenetic systems, allowing the entire device to be implanted subcutaneously. With a radio-frequency (RF) power source and controller, this implant produces sufficient light power for optogenetic stimulation with minimal tissue heating (<1 degrees C). We show how three adaptations of the implant allow for untethered optogenetic control throughout the nervous system (brain, spinal cord and peripheral nerve endings) of behaving mice. This technology opens the door for optogenetic experiments in which animals are able to behave naturally with optogenetic manipulation of both central and peripheral targets. PMID- 26280331 TI - ChIPmentation: fast, robust, low-input ChIP-seq for histones and transcription factors. AB - Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is widely used to map histone marks and transcription factor binding throughout the genome. Here we present ChIPmentation, a method that combines chromatin immunoprecipitation with sequencing library preparation by Tn5 transposase ('tagmentation'). ChIPmentation introduces sequencing-compatible adaptors in a single-step reaction directly on bead-bound chromatin, which reduces time, cost and input requirements, thus providing a convenient and broadly useful alternative to existing ChIP-seq protocols. PMID- 26280332 TI - Superconductivity: Extraordinarily conventional. PMID- 26280333 TI - Conventional superconductivity at 203 kelvin at high pressures in the sulfur hydride system. AB - A superconductor is a material that can conduct electricity without resistance below a superconducting transition temperature, Tc. The highest Tc that has been achieved to date is in the copper oxide system: 133 kelvin at ambient pressure and 164 kelvin at high pressures. As the nature of superconductivity in these materials is still not fully understood (they are not conventional superconductors), the prospects for achieving still higher transition temperatures by this route are not clear. In contrast, the Bardeen-Cooper Schrieffer theory of conventional superconductivity gives a guide for achieving high Tc with no theoretical upper bound--all that is needed is a favourable combination of high-frequency phonons, strong electron-phonon coupling, and a high density of states. These conditions can in principle be fulfilled for metallic hydrogen and covalent compounds dominated by hydrogen, as hydrogen atoms provide the necessary high-frequency phonon modes as well as the strong electron phonon coupling. Numerous calculations support this idea and have predicted transition temperatures in the range 50-235 kelvin for many hydrides, but only a moderate Tc of 17 kelvin has been observed experimentally. Here we investigate sulfur hydride, where a Tc of 80 kelvin has been predicted. We find that this system transforms to a metal at a pressure of approximately 90 gigapascals. On cooling, we see signatures of superconductivity: a sharp drop of the resistivity to zero and a decrease of the transition temperature with magnetic field, with magnetic susceptibility measurements confirming a Tc of 203 kelvin. Moreover, a pronounced isotope shift of Tc in sulfur deuteride is suggestive of an electron phonon mechanism of superconductivity that is consistent with the Bardeen-Cooper Schrieffer scenario. We argue that the phase responsible for high-Tc superconductivity in this system is likely to be H3S, formed from H2S by decomposition under pressure. These findings raise hope for the prospects for achieving room-temperature superconductivity in other hydrogen-based materials. PMID- 26280334 TI - Structural insights into the bacterial carbon-phosphorus lyase machinery. AB - Phosphorus is required for all life and microorganisms can extract it from their environment through several metabolic pathways. When phosphate is in limited supply, some bacteria are able to use phosphonate compounds, which require specialized enzymatic machinery to break the stable carbon-phosphorus (C-P) bond. Despite its importance, the details of how this machinery catabolizes phosphonates remain unknown. Here we determine the crystal structure of the 240 kilodalton Escherichia coli C-P lyase core complex (PhnG-PhnH-PhnI-PhnJ; PhnGHIJ), and show that it is a two-fold symmetric hetero-octamer comprising an intertwined network of subunits with unexpected self-homologies. It contains two potential active sites that probably couple phosphonate compounds to ATP and subsequently hydrolyse the C-P bond. We map the binding site of PhnK on the complex using electron microscopy, and show that it binds to a conserved insertion domain of PhnJ. Our results provide a structural basis for understanding microbial phosphonate breakdown. PMID- 26280335 TI - An atomic structure of human gamma-secretase. AB - Dysfunction of the intramembrane protease gamma-secretase is thought to cause Alzheimer's disease, with most mutations derived from Alzheimer's disease mapping to the catalytic subunit presenilin 1 (PS1). Here we report an atomic structure of human gamma-secretase at 3.4 A resolution, determined by single-particle cryo electron microscopy. Mutations derived from Alzheimer's disease affect residues at two hotspots in PS1, each located at the centre of a distinct four transmembrane segment (TM) bundle. TM2 and, to a lesser extent, TM6 exhibit considerable flexibility, yielding a plastic active site and adaptable surrounding elements. The active site of PS1 is accessible from the convex side of the TM horseshoe, suggesting considerable conformational changes in nicastrin extracellular domain after substrate recruitment. Component protein APH-1 serves as a scaffold, anchoring the lone transmembrane helix from nicastrin and supporting the flexible conformation of PS1. Ordered phospholipids stabilize the complex inside the membrane. Our structure serves as a molecular basis for mechanistic understanding of gamma-secretase function. PMID- 26280337 TI - Multimetallic catalysed cross-coupling of aryl bromides with aryl triflates. AB - The advent of transition-metal catalysed strategies for forming new carbon-carbon bonds has revolutionized the field of organic chemistry, enabling the efficient synthesis of ligands, materials, and biologically active molecules. In cases where a single metal fails to promote a selective or efficient transformation, the synergistic cooperation of two distinct catalysts--multimetallic catalysis- can be used instead. Many important reactions rely on multimetallic catalysis, such as the Wacker oxidation of olefins and the Sonogashira coupling of alkynes with aryl halides, but this approach has largely been limited to the use of metals with distinct reactivities, with only one metal catalyst undergoing oxidative addition. Here, we demonstrate that cooperativity between two group 10 metal catalysts--(bipyridine)nickel and (1,3 bis(diphenylphosphino)propane)palladium--enables a general cross-Ullmann reaction (the cross-coupling of two different aryl electrophiles). Our method couples aryl bromides with aryl triflates directly, eliminating the use of arylmetal reagents and avoiding the challenge of differentiating between multiple carbon-hydrogen bonds that is required for direct arylation methods. Selectivity can be achieved without an excess of either substrate and originates from the orthogonal reactivity of the two catalysts and the relative stability of the two arylmetal intermediates. While (1,3-bis(diphenylphosphino)propane)palladium reacts preferentially with aryl triflates to afford a persistent intermediate, (bipyridine)nickel reacts preferentially with aryl bromides to form a transient, reactive intermediate. Although each catalyst forms less than 5 per cent cross coupled product in isolation, together they are able to achieve a yield of up to 94 per cent. Our results reveal a new method for the synthesis of biaryls, heteroaryls, and dienes, as well as a general mechanism for the selective transfer of ligands between two metal catalysts. We anticipate that this reaction will simplify the synthesis of pharmaceuticals, many of which are currently made with pre-formed organometallic reagents, and lead to the discovery of new multimetallic reactions. PMID- 26280338 TI - Substance Abuse and Other Adverse Outcomes for Military-Connected Youth in California: Results From a Large-Scale Normative Population Survey. AB - IMPORTANCE: Military families and military-connected youth exhibit significant strengths; however, a sizeable proportion of these families appear to be struggling in the face of war-related stressors. Understanding the consequences of war is critical as a public health concern and because additional resources may be needed to support military families. OBJECTIVE: To determine whether rates of adverse outcomes are higher for military-connected adolescents during war compared with nonmilitary peers. DESIGN, SETTING, AND PARTICIPANTS: This study is a secondary data analysis of a large, normative, and geographically comprehensive administrative data set (2013 California Healthy Kids Survey) to determine whether military-connected youth are at risk for adverse outcomes, including substance use, experiencing violence and harassment, and weapon carrying, during wartime. These outcomes are of particular concern because they affect socioemotional adjustment and academic success. Data were collected in March and April 2013 and participants included 54,679 military-connected and 634,034 nonmilitary-connected secondary school students from public civilian schools in every county and almost all school districts in California. MAIN OUTCOMES AND MEASURES: Outcomes included lifetime and recent use of alcohol, tobacco, marijuana, prescription medications, and other drugs, as well as experiences of physical and nonphysical violence and harassment and weapon carrying during the last year. RESULTS: Multivariable logistic regression models indicated that military-connected youth had greater odds of substance use, experience of physical violence and nonphysical harassment, and weapon carrying. For example, military-connected youth had 73% greater odds of recent other drug use (eg, cocaine and lysergic acid diethylamide; odds ratio [OR], 1.73; 95% CI, 1.66-1.80) and twice the odds of bringing a gun to school (OR, 2.20; 95% CI, 2.10-2.30) compared with nonmilitary-connected peers. Their odds of being threatened with a weapon or being in a fight were also significantly higher than their civilian counterparts (OR, 1.87; 95% CI, 1.80-1.95 and OR, 1.67; 95% CI, 1.62-1.71, respectively). CONCLUSIONS AND RELEVANCE: Most military-connected youth demonstrate resilience. However, results suggest that during wartime, military connected youth are at increased risk for adverse outcomes. Further, when compared with data from 2011, the rates of these negative outcomes appear to be increasing. These findings suggest a need to identify and intervene with military connected adolescents and reflect a larger concern regarding the well-being of military families during wartime. PMID- 26280336 TI - Architecture of the synaptotagmin-SNARE machinery for neuronal exocytosis. AB - Synaptotagmin-1 and neuronal SNARE proteins have central roles in evoked synchronous neurotransmitter release; however, it is unknown how they cooperate to trigger synaptic vesicle fusion. Here we report atomic-resolution crystal structures of Ca(2+)- and Mg(2+)-bound complexes between synaptotagmin-1 and the neuronal SNARE complex, one of which was determined with diffraction data from an X-ray free-electron laser, leading to an atomic-resolution structure with accurate rotamer assignments for many side chains. The structures reveal several interfaces, including a large, specific, Ca(2+)-independent and conserved interface. Tests of this interface by mutagenesis suggest that it is essential for Ca(2+)-triggered neurotransmitter release in mouse hippocampal neuronal synapses and for Ca(2+)-triggered vesicle fusion in a reconstituted system. We propose that this interface forms before Ca(2+) triggering, moves en bloc as Ca(2+) influx promotes the interactions between synaptotagmin-1 and the plasma membrane, and consequently remodels the membrane to promote fusion, possibly in conjunction with other interfaces. PMID- 26280339 TI - Metabolic Syndrome: Foreword. PMID- 26280340 TI - Metabolic Syndrome: Insulin Resistance and Prediabetes. AB - Metabolic syndrome is a cluster of conditions that synergistically increase the risk of cardiovascular disease, type 2 diabetes, and premature mortality. The components are abdominal obesity, impaired glucose metabolism, dyslipidemia, and hypertension. Prediabetes, which is a combination of excess body fat and insulin resistance, is considered an underlying etiology of metabolic syndrome. Prediabetes manifests as impaired fasting glucose and/or impaired glucose tolerance. Impaired fasting glucose is defined as a fasting blood glucose level of 100 to 125 mg/dL; impaired glucose tolerance requires a blood glucose level of 140 to 199 mg/dL 2 hours after a 75-g oral intake of glucose. In patients with prediabetes, the rate of progression to diabetes within 3 years can be decreased by approximately 58% with lifestyle modifications. These include weight loss through exercise (30 minutes or more of moderate physical activity on most, preferably all, days of the week) and dietary modifications. Recommended diets are high in fruits, vegetables, whole grains, and fish. Consumption of sweetened beverages, including diet soda, should be avoided. For patients who do not achieve goals with lifestyle modifications, metformin can be considered. Weight loss drugs and bariatric surgery are appropriate for select patients. Hypertension and dyslipidemia should be managed according to current guidelines. PMID- 26280341 TI - Metabolic Syndrome: Hyperlipidemia. AB - Metabolic syndrome is associated with an elevated risk of cardiovascular disease and premature mortality. When metabolic syndrome includes lipid abnormalities, management goals are weight loss and cardiovascular risk management through lifestyle modifications (eg, diet, exercise), and, when appropriate, lowering of lipid levels with pharmacotherapy. Healthy diets are recommended, particularly the Mediterranean diet. Patients also should set a goal of at least 30 minutes of moderate to vigorous exercise on most, preferably all, days of the week. Guidelines provide criteria for statin treatment based on overall cardiovascular risk. High-intensity statin treatment (eg, rosuvastatin 20 to 40 mg, atorvastatin 40 to 80 mg) typically is recommended unless the patient cannot tolerate therapy. Approximately 5% of patients experience statin-induced myalgia, in which case moderate-intensity treatment can be tried. Lipid levels should be reevaluated 4 to 12 weeks after initiating therapy; lipid levels can be measured without fasting. A lack of improvement often indicates nonadherence. Bile acid sequestrants, fibric acids, and niacin can be used if other drugs are not tolerated. The evidence to support use of integrative medicine is limited, but the strongest evidence of benefit is for garlic (Allium sativum). PMID- 26280342 TI - Metabolic Syndrome: Nonalcoholic Fatty Liver Disease. AB - Although nonalcoholic fatty liver disease (NAFLD) is not one of the defining criteria for metabolic syndrome, it is a common hepatic manifestation. NAFLD includes a spectrum of histologic findings ranging from simple steatosis, known as nonalcoholic fatty liver, to nonalcoholic steatohepatitis (NASH). To make the diagnosis of NAFLD, other etiologies of steatosis or hepatitis, such as hepatotoxic drugs, excessive alcohol intake, congenital errors of metabolism, or viral hepatitis, must be ruled out. After ruling out other conditions, the diagnosis of NAFLD often is made clinically, but a definitive diagnosis of NASH requires liver biopsy. As with other complications of metabolic syndrome, insulin resistance is thought to be an underlying etiology of NAFLD. Management strategies attempt to reverse or improve insulin resistance while minimizing liver damage. The strongest evidence supports lifestyle modifications with weight loss, but there is some evidence to support bariatric surgery, medical therapy with insulin-sensitizing agents, and/or pharmacotherapy to promote weight loss. Cardiovascular disease is the major cause of mortality in patients with NAFLD, so management must include modification of cardiovascular risk factors. PMID- 26280343 TI - Metabolic Syndrome: Polycystic Ovary Syndrome. AB - Polycystic ovary syndrome (PCOS) is a heterogeneous condition characterized by androgen excess, ovulatory dysfunction, and polycystic ovaries. It is the most common endocrinopathy among women of reproductive age, affecting between 6.5% and 8% of women, and is the most common cause of infertility. Insulin resistance is almost always present in women with PCOS, regardless of weight, and they often develop diabetes and metabolic syndrome. The Rotterdam criteria are widely used for diagnosis. These criteria require that patients have at least two of the following conditions: hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. The diagnosis of PCOS also requires exclusion of other potential etiologies of hyperandrogenism and ovulatory dysfunction. The approach to PCOS management differs according to the presenting symptoms and treatment goals, particularly the patient's desire for pregnancy. Weight loss through dietary modifications and exercise is recommended for patients with PCOS who are overweight. Oral contraceptives are the first-line treatment for regulating menstrual cycles and reducing manifestations of hyperandrogenism, such as acne and hirsutism. Clomiphene is the first-line drug for management of anovulatory infertility. Metformin is recommended for metabolic abnormalities such as prediabetes, and a statin should be prescribed for cardioprotection if the patient meets standard criteria for statin therapy. PMID- 26280344 TI - Obstacles to Developing Cost-Lowering Health Technology: The Inventor's Dilemma. PMID- 26280345 TI - Sleep Deprivation Is Associated with Bicycle Accidents and Slip and Fall Injuries in Korean Adolescents. AB - OBJECTIVE: This study sought to evaluate associations between sleep time and bicycle accidents, falls under various circumstances, and dental injuries in adolescents. METHODS: A total of 61,696 participants ranging from 12 to 18 years of age who completed the Korea Youth Risk Behavior Web-based Survey (KYRBWS) in 2013 were enrolled in this study. Bicycle riding accidents were analyzed for 17,232 bicycle-riding participants. Data were collected regarding the weekday sleep duration for the most recent 7 days, which was categorized as < 5.5 h, 5.5 6.5 h, 6.5-7.5 h, or >= 7.5 h per day, and the incidence of bicycle accidents, slips and falls under various circumstances, and dental injuries in the most recent 12 months. Adjusted odds ratios (aORs) were calculated among sleep groups for bicycle accidents, slips and falls, and dental injuries using simple and multiple logistic regression analyses with complex sampling. RESULTS: Bicycle riding accidents and slips and falls in classrooms, corridors, the ground, toilets, stairs, and other unspecified situations showed positive correlations with sleep deprivation. Comparisons of groups with >= 7.5 h sleep, < 5.5 h, 5.5 6.5 h sleep, and 6.5-7.5 h sleep revealed increased associations with slips and falls under various circumstances. In particular, the aORs were higher in the groups with less sleep (aOR of the 5.5 h group > the 5.5-6.5 h group > the 6.5 7.5 h group). There was no significant relationship between sleep deprivation and dental injury. CONCLUSIONS: This study demonstrated that sleep deprivation among Korean adolescents was associated with bicycle accidents and falls at home and school. Thus, adequate sleep may be needed to prevent accidents and falls. PMID- 26280347 TI - Stereoselective Synthesis of 4-Substituted Cyclic Sulfamidate-5-Phosphonates by Using Rh-Catalyzed, Asymmetric Transfer Hydrogenation with Accompanying Dynamic Kinetic Resolution. AB - Dynamic kinetic resolution driven, asymmetric transfer hydrogenation of 4 substituted cyclic sulfamidate imine-5-phosphonates produces the corresponding cyclic sulfamidate-5-phosphonates. The process employs a HCO2H/Et3N mixture as the hydrogen source and the chiral Rh catalysts, (R,R)- or (S,S)-Cp*RhCl(TsDPEN), and it takes place at room temperature within 1 h with high yields and high levels of stereoselectivity. PMID- 26280346 TI - Higher Matrix Stiffness Upregulates Osteopontin Expression in Hepatocellular Carcinoma Cells Mediated by Integrin beta1/GSK3beta/beta-Catenin Signaling Pathway. AB - Increased stromal stiffness is associated with hepatocellular carcinoma (HCC) development and progression. However, the molecular mechanism by which matrix stiffness stimuli modulate HCC progress is largely unknown. In this study, we explored whether matrix stiffness-mediated effects on osteopontin (OPN) expression occur in HCC cells. We used a previously reported in vitro culture system with tunable matrix stiffness and found that OPN expression was remarkably upregulated in HCC cells with increasing matrix stiffness. Furthermore, the phosphorylation level of GSK3beta and the expression of nuclear beta-catenin were also elevated, indicating that GSK3beta/beta-catenin pathway might be involved in OPN regulation. Knock-down analysis of integrin beta1 showed that OPN expression and p-GSK3beta level were downregulated in HCC cells grown on high stiffness substrate compared with controls. Simultaneously, inhibition of GSK-3beta led to accumulation of beta-catenin in the cytoplasm and its enhanced nuclear translocation, further triggered the rescue of OPN expression, suggesting that the integrin beta1/GSK-3beta/beta-catenin pathway is specifically activated for matrix stiffness-mediated OPN upregulation in HCC cells. Tissue microarray analysis confirmed that OPN expression was positively correlated with the expression of LOX and COL1. Taken together, high matrix stiffness upregulated OPN expression in HCC cells via the integrin beta1/GSK-3beta/beta-catenin signaling pathway. It highlights a new insight into a pathway involving physical mechanical signal and biochemical signal molecules which contributes to OPN expression in HCC cells. PMID- 26280348 TI - Radiation-Induced Glycogen Accumulation Detected by Single Cell Raman Spectroscopy Is Associated with Radioresistance that Can Be Reversed by Metformin. AB - Altered cellular metabolism is a hallmark of tumor cells and contributes to a host of properties associated with resistance to radiotherapy. Detection of radiation-induced biochemical changes can reveal unique metabolic pathways affecting radiosensitivity that may serve as attractive therapeutic targets. Using clinically relevant doses of radiation, we performed label-free single cell Raman spectroscopy on a series of human cancer cell lines and detected radiation induced accumulation of intracellular glycogen. The increase in glycogen post irradiation was highest in lung (H460) and breast (MCF7) tumor cells compared to prostate (LNCaP) tumor cells. In response to radiation, the appearance of this glycogen signature correlated with radiation resistance. Moreover, the buildup of glycogen was linked to the phosphorylation of GSK-3beta, a canonical modulator of cell survival following radiation exposure and a key regulator of glycogen metabolism. When MCF7 cells were irradiated in the presence of the anti-diabetic drug metformin, there was a significant decrease in the amount of radiation induced glycogen. The suppression of glycogen by metformin following radiation was associated with increased radiosensitivity. In contrast to MCF7 cells, metformin had minimal effects on both the level of glycogen in H460 cells following radiation and radiosensitivity. Our data demonstrate a novel approach of spectral monitoring by Raman spectroscopy to assess changes in the levels of intracellular glycogen as a potential marker and resistance mechanism to radiation therapy. PMID- 26280349 TI - Regret Expression and Social Learning Increases Delay to Sexual Gratification. AB - OBJECTIVE: Modification and prevention of risky sexual behavior is important to individuals' health and public health policy. This study employed a novel sexual discounting task to elucidate the effects of social learning and regret expression on delay to sexual gratification in a behavioral task. METHODS: Amazon Mechanical Turk Workers were assigned to hear one of three scenarios about a friend who engages in similar sexual behavior. The scenarios included a positive health consequence, a negative health consequence or a negative health consequence with the expression of regret. After reading one scenario, participants were asked to select from 60 images, those with whom they would have casual sex. Of the selected images, participants chose one image each for the person they most and least want to have sex with and person most and least likely to have a sexually transmitted infection. They then answered questions about engaging in unprotected sex now or waiting some delay for condom-protected sex in each partner condition. RESULTS: Results indicate that the negative health outcome scenario with regret expression resulted in delayed sexual gratification in the most attractive and least STI partner conditions, whereas in the least attractive and most STI partner conditions the negative health outcome with and without regret resulted in delayed sexual gratification. CONCLUSIONS: Results suggest that the sexual discounting task is a relevant laboratory measure and the framing of information to include regret expression may be relevant for prevention of risky sexual behavior. PMID- 26280350 TI - Voice disorders in the elderly: A national database study. AB - OBJECTIVES/HYPOTHESIS: To determine the type, frequency, and factors associated with voice disorders in the elderly. STUDY DESIGN: Retrospective analysis of data from a large national administrative US claims database. METHODS: Elderly outpatients (>65 years old) with a laryngeal/voice disorder (LVD) diagnosis based on International Classification of Diseases, Ninth Revision, Clinical Modification codes from January 1, 2004 to December 31, 2008, seen by an otolaryngologist or primary care physician (PCP) were included. Data regarding age, gender, comorbid conditions, geographic location, employment history, and type of physician providing the diagnosis were collected, and multiple logistic regression was used to determine the influence of these factors in otolaryngologist-determined LVD diagnoses. RESULTS: Of the almost 55 million individuals in the database, 60,773 unique patients (mean age = 74.9 years, standard deviation = 6.6 years, range = 65-105 years) had an encounter with a PCP or otolaryngologist and received an LVD diagnosis. The most frequent diagnoses overall were acute and chronic laryngitis, nonspecific dysphonia, and benign vocal fold lesions. PCPs more commonly diagnosed acute laryngitis, whereas otolaryngologists more commonly diagnosed nonspecific dysphonia and laryngeal changes/lesions. In the otolaryngology group, odds of nonspecific dysphonia and vocal fold paralysis/paresis diagnoses increased with advancing age, whereas benign laryngeal pathology, and acute and chronic laryngitis decreased. As compared to men, women had lower odds of paralysis/paresis and laryngeal cancer but higher odds of acute laryngitis and nonspecific dysphonia. Odds of specific LVDs also varied depending upon comorbid conditions and geographic location. CONCLUSIONS: Age, gender, comorbid conditions, geographic location, and physician type were significantly associated with specific LVD diagnoses within the elderly. LEVEL OF EVIDENCE: 4. PMID- 26280351 TI - Determination of Corynebacterium pseudotuberculosis prevalence and antimicrobial susceptibility pattern of isolates from lymph nodes of sheep and goats at an organic export abattoir, Modjo, Ethiopia. AB - Corynebacterium pseudotuberculosis is the causative agent of caseous lymphadenitis, a suppurative abscessation in the superficial and internal lymph nodes and internal organs of small ruminants. This study was conducted on the superficial lymph nodes and carcasses of 768 small ruminants slaughtered at a slaughterhouse during the study period; 82 had abscesses or caseous lymphadenitis. The most frequent sites of abscesses in goats were the prescapular (34, 5.54%) and prefemoral lymph nodes (24, 3.91%) respectively. Similar patterns were observed in sheep. The prevalence of caseous lymphadenitis was found to be significantly higher in adult than in young animals, in both species (P < 0.05). The age-wise prevalence rates of lesions on post-mortem inspection, at 95% CI, were 2.7% (2.3-3.1%) and 3.1% (2.8-3.4%) in young sheep and goats, respectively, and 24.4% (17.4-31.4%) and 27.5% (23.8-31.2%) in adult sheep and goats respectively. Corynebacterium pseudotuberculosis isolates were recovered from 72% (59/82) of animals found to have post-mortem evidence of abscesses. The Coryne. pseudotuberculosis isolates were susceptible to the antibiotics norfloxacin, tetracycline, doxycyline HCl and kanamycine; however, resistance was observed against ampicillin, clindamycin and doxycyline HCl. In conclusion, this study reported the magnitude of the problem in the country for the first time and the authors recommend a thorough investigation of wider study areas. SIGNIFICANCE AND IMPACT OF THE STUDY: This work presents data on the prevalence of caseous lymphadenitis in slaughtered sheep and goats as well as the isolation and antibiotic susceptibility pattern of Corynebacterium pseudotuberculosis for the first time in Ethiopia. The carcasses of small ruminants are the major livestock product exported from the country and serves as an important source of foreign currency. Assessing the impact of diseases such as caseous lymphadenitis in the industry would be of great significance. This work forms initial data that call for further wider investigations to gain complete understanding of its impact in the country. PMID- 26280352 TI - Transient State Machine Enabled from the Colliding and Coalescence of a Swarm of Autonomously Running Liquid Metal Motors. AB - Internally triggered motion of an object owns important potential in diverse application areas ranging from micromachines, actuator or sensor, to self assembly of superstructures. A new conceptual liquid metal machine style has been presented here: the transient state machine that can work as either a large size robot, partial running elements, or just divide spontaneously running swarm of tiny motors. According to need, the discrete droplet machines as quickly generated through injecting the stream of a large liquid metal machine can combine back again to the original one. Over the process, each tiny machine just keeps its running, colliding, bouncing, or adhesion states until finally assembling into a single machine. Unlike the commonly encountered rigid machines, such transient state system can be reversible in working shapes. Depending on their surface tension, the autonomously traveling droplet motors can experience bouncing and colliding before undergoing total coalescence, arrested coalescence, or total bounce. This finding would help mold unconventional robot in the sense of transient state machine that could automatically transform among different geometries such as a single or swarm, small or large size, assembling and interaction, etc. It refreshes people's basic understandings on machines, liquid metal materials, fluid mechanics, and micromotors. PMID- 26280353 TI - First Study on Phosphonite-Coordinated Ruthenium Sensitizers for Efficient Photocatalytic Hydrogen Evolution. AB - For the first time we report the design and syntheses of phosphonite coordinated ruthenium(II) sensitizers bearing CNN ligand and/or terpyridine derivatives carboxylate anchor (GS11, GS12. and GS13) and its application for hydrogen production over Pt-TiO2 system. These heteroleptic complexes exhibit broad metal to-ligand charge transfer transition band over the whole visible regime extending up to 900 nm. DFT calculations of these complexes show that the HOMO is distributed over the Ru and Cl atom whereas; LUMO is localized on the polypyridile ligand, which are anchored on TiO2 surface. Among the sensitizers tested for photocatalytic hydrogen evolution, GS12 exhibited a maximum turnover number (TON) 8605 (for 8 h), which is very high compared to the reference sensitizer (N719) with TON 163 under similar evaluation condition. The dependence of the hydrogen evolution rate at different pH using GS11, GS12, GS13, and DX-1 sensitized Pt-TiO2 has been studied and the maximum H2 production yield was obtained at pH 7 for all sensitizers. PMID- 26280354 TI - Colorectal Polyps Missed with Optical Colonoscopy Despite Previous Detection and Localization with CT Colonography. AB - PURPOSE: To retrospectively evaluate and characterize nondiminutive colorectal polyps prospectively detected by using computed tomographic (CT) colonography but not confirmed with subsequent nonblinded optical colonoscopy (OC). MATERIALS AND METHODS: This study was institutional review board approved; the need for signed informed consent was waived. Over 113 months, 9336 adults (mean age, 57.1 years) underwent CT colonography, which yielded 2606 nondiminutive (>=6 mm) polyps. Of 1731 polyps that underwent subsequent nonblinded OC (ie, endoscopists provided advanced knowledge of specific polyp size, location, and morphologic appearance at CT colonography), 181 (10%) were not confirmed with initial endoscopy (ie, discordant), of which 37 were excluded (awaiting or lost to follow-up). After discordant polyp review, 66 of the 144 lesions were categorized as likely CT colonography false-positive findings (no further action) and 78 were categorized as potential OC false-negative (FN) findings. RESULTS: Thirty-one of 144 (21.5%) of all discordant lesions were confirmed as FN findings at OC, including 40% (31 of 78) of those with OC and/or CT colonography follow-up. OC FN lesions were an average of 8.5 mm +/- 3.3 in diameter and were identified with higher confidence at prospective CT colonography (on a 3-point confidence scale: mean, 2.8 vs 2.3; P = .001). OC FN findings were more likely than concordant polyps to be located in the right colon (respectively, 71% [22 of 31] vs 47% [723 of 1535]; P = .010). Most (81% [21 of 26]) OC FN lesions that were ultimately resected were neoplastic (adenomas or serrated lesions), of which 43% (nine of 21) were characterized as advanced lesions, and 89% (eight of nine) of advanced lesions occurred in the right colon. CONCLUSION: In clinical practice, polyps prospectively identified with CT colonography but not confirmed with subsequent nonblinded (ie, despite a priori knowledge of the CT colonography findings) OC require additional review because a substantial proportion may be FN findings. Most FN findings found with OC demonstrated clinically significant histopathologic results, and a majority of advanced lesions occurred in the right colon. PMID- 26280355 TI - Category cued recall evokes a generate-recognize retrieval process. AB - The experiments reported here were designed to replicate and extend McCabe, Roediger, and Karpicke's (2011) finding that retrieval in category cued recall involves both controlled and automatic processes. The extension entailed identifying whether distinctive encoding affected 1 or both of these 2 processes. The first experiment successfully replicated McCabe et al., but the second, which added a critical baseline condition, produced data inconsistent with a 2 independent process model of recall. The third experiment provided evidence that retrieval in category cued recall reflects a generate-recognize strategy, with the effect of distinctive processing being localized to recognition. Overall, the data suggest that category cued recall evokes a generate-recognize retrieval strategy and that the subprocesses underlying this strategy can be dissociated as a function of distinctive versus relational encoding processes. PMID- 26280356 TI - Chemicals on plant surfaces as a heretofore unrecognized, but ecologically informative, class for investigations into plant defence. AB - Plants produce and utilize a great diversity of chemicals for a variety of physiological and ecological purposes. Many of these chemicals defend plants against herbivores, pathogens and competitors. The location of these chemicals varies within the plant, some are located entirely within plant tissues, others exist in the air- (or water-) space around plants, and still others are secreted onto plant surfaces as exudates. I argue herein that the location of a given defensive chemical has profound implications for its ecological function; specifically, I focus on the characteristics of chemical defences secreted onto plant surfaces. Drawing from a broad literature encompassing ecology, evolution, taxonomy and physiology, I found that these external chemical defences (ECDs) are common and widespread in plants and algae; hundreds of examples have been detailed, yet they are not delineated as a separate class from internal chemical defences (ICDs). I propose a novel typology for ECDs and, using existing literature, explore the ecological consequences of the hypothesized unique characteristics of ECDs. The axis of total or proportional investment in ECDs versus ICDs should be considered as one axis of investment by a plant, in the same way as quantitative versus qualitative chemical defences or induced versus constitutive defences is considered. The ease of manipulating ECDs in many plant systems presents a powerful tool to help test plant defence theory (e.g. optimal defence). The framework outlined here integrates various disciplines of botany and ecology and suggests a need for further examinations of exudates in a variety of contexts, as well as recognition of the effects of within-plant localization of defences. PMID- 26280357 TI - Mass spectrometry in the pharmacokinetic studies of anticancer natural products. AB - In the history of medicine, nature has represented the main source of medical products. Indeed, the therapeutic use of plants certainly goes back to the Sumerian and Hippocrates and nowadays nature still represents the major source for new drugs discovery. Moreover, in the cancer treatment, drugs are either natural compounds or have been developed from naturally occurring parent compounds firstly isolated from plants and microbes from terrestrial and marine environment. A critical element of an anticancer drug is represented by its severe toxicities and, after administration, the drug concentrations have to remain in an appropriate range to be effective. Anyway, the drug dosage defined during the clinical studies could be inappropriate for an individual patient due to differences in drug absorption, metabolism and excretion. For this reason, personalized medicine, based on therapeutic drug monitoring (TDM), represents one of most important challenges in cancer therapy. Mass spectrometry sensitivity, specificity and fastness lead to elect this technique as the Golden Standard for pharmacokinetics and drug metabolism studies therefore for TDM. This review focuses on the mass spectrometry-based methods developed for pharmacokinetic quantification in human plasma of anticancer drugs derived from natural sources and already used in clinical practice. Particular emphasis was placed both on the pre-analytical and analytical steps, such as: sample preparation procedures, sample size required by the analysis and the limit of quantification of drugs and metabolites to give some insights on the clinical practice applicability. (c) 2015 Wiley Periodicals, Inc. Mass Spec Rev. 36:213-251, 2017. PMID- 26280358 TI - Live-Cell Labeling of Specific Protein Glycoforms by Proximity-Enhanced Bioorthogonal Ligation. AB - Reagents for detecting post-translational modifications in the context of their protein scaffold are powerful tools, but are challenging to develop for glycosylated epitopes. We describe a strategy for detecting protein-specific glycosylation through the use of cyclooctyne-aptamer conjugates. These molecules selectively ligate to azidosugar-labeled glycans exclusively on a target protein on live cells. We characterized aptamer conjugates against two different cell surface glycoproteins and show that these reagents are amenable to detecting protein sialoforms by mass spectrometry, Western blotting, and flow cytometry. Given the abundance of aptamers that bind cell surface targets, we expect this technology will be a useful platform for investigating the roles of protein specific glycosylation in various cellular contexts. PMID- 26280359 TI - Incidence of testicular germ cell tumors among US men by census region. AB - BACKGROUND: The incidence of testicular germ cell tumors (TGCTs) in the United States is notably higher among white men versus other men. Previously, however, it was reported that rates were rising among Hispanics in certain areas. To determine whether this finding was evident in a wider area of the United States, data from 39 US cancer registries were examined. METHODS: Racial/ethnic-specific incidence rates per 100,000 man-years were calculated overall and by census region for the period of 1998-2011. Annual percentage changes (APCs) were estimated, and joinpoint models were fit. Differences in incidence by region were examined with the Wald test. RESULTS: From 1998 to 2011, 88,993 TGCTs were recorded. The TGCT incidence was highest among non-Hispanic whites (6.57 per 100,000), who were followed by Hispanics (3.88), American Indians/Alaska Natives (2.88), Asians/Pacific Islanders (A/PIs; 1.60), and non-Hispanic blacks (1.20). The incidence significantly increased among Hispanics (APC, 2.31; P < .0001), with rates rising in all regions except the South. Rates rose slightly among non Hispanic whites (APC, 0.51; P = .0076). Significant differences in rates by region were seen for Hispanics (P = .0001), non-Hispanic whites (P < .0001), and A/PIs (P < .0001), with the highest rates among Hispanics in the West and with the highest rates among non-Hispanic whites and A/PIs in the Northeast. CONCLUSIONS: Although the incidence of TGCTs remained highest among non-Hispanic whites between 1998 and 2011, the greatest increase was experienced by Hispanics. Rising rates of TGCTs among Hispanics in the United States suggest that future attention is warranted. Reasons for the increase may include variability in birthplace, changing exposures, genetic susceptibility, and the length of US residence. PMID- 26280360 TI - Slowed Search in the Context of Unimpaired Grouping in Autism: Evidence from Multiple Conjunction Search. AB - In multiple conjunction search, the target is not known in advance but is defined only with respect to the distractors in a given search array, thus reducing the contributions of bottom-up and top-down attentional and perceptual processes during search. This study investigated whether the superior visual search skills typically demonstrated by individuals with autism spectrum disorder (ASD) would be evident in multiple conjunction search. Thirty-two children with ASD and 32 age- and nonverbal IQ-matched typically developing (TD) children were administered a multiple conjunction search task. Contrary to findings from the large majority of studies on visual search in ASD, response times of individuals with ASD were significantly slower than those of their TD peers. Evidence of slowed performance in ASD suggests that the mechanisms responsible for superior ASD performance in other visual search paradigms are not available in multiple conjunction search. Although the ASD group failed to exhibit superior performance, they showed efficient search and intertrial priming levels similar to the TD group. Efficient search indicates that ASD participants were able to group distractors into distinct subsets. In summary, while demonstrating grouping and priming effects comparable to those exhibited by their TD peers, children with ASD were slowed in their performance on a multiple conjunction search task, suggesting that their usual superior performance in visual search tasks is specifically dependent on top-down and/or bottom-up attentional and perceptual processes. PMID- 26280361 TI - A NONOVARY-SPECIFIC VITELLOGENIN RECEPTOR FROM THE ORIENTAL FRUIT FLY, Bactrocera dorsalis (HENDEL). AB - The yolk protein precursor, vitellogenin (Vg), is absorbed into growing oocytes via receptor-mediated endocytosis for embryonic development. In this study, a Vg receptor (VgR) cDNA of the oriental fruit fly (Bactrocera dorsalis Hendel) was cloned via RT-PCR and RACE (GenBank accession no. KR535603) and its expression analyzed. The BdVgR cDNA has a length of 6,585 bp encoding 1,923 amino acids. It has a conserved motif arrangement with other insect VgRs, and showed high identity to the B. cucurbitae VgR (91.4%). The expression of BdVgR mRNA and proteins was shown in both ovary and fat body. This is the first report on a nonovary-specific VgR from a nonsocial insect. In ovary, the expression of BdVgR mRNA and proteins was inconsistent, with the transcription, but not protein, level high on D0. In fat body, the expression levels of BdVgR mRNA and proteins were high on days 5 and 6. The function of BdVgR in the fat body is not clear. However, it may be involved in reuptake of yolk proteins from the hemolymph as an amino acid reservoir or as autocrine regulation of yolk protein expression. PMID- 26280362 TI - Parametrization of macrolide antibiotics using the force field toolkit. AB - Macrolides are an important class of antibiotics that target the bacterial ribosome. Computer simulations of macrolides are limited as specific force field parameters have not been previously developed for them. Here, we determine CHARMM compatible force field parameters for erythromycin, azithromycin, and telithromycin, using the force field toolkit (ffTK) plugin in VMD. Because of their large size, novel approaches for parametrizing them had to be developed. Two methods for determining partial atomic charges, from interactions with TIP3P water and from the electrostatic potential, as well as several approaches for fitting the dihedral parameters were tested. The performance of the different parameter sets was evaluated by molecular dynamics simulations of the macrolides in ribosome, with a distinct improvement in maintenance of key interactions observed after refinement of the initial parameters. Based on the results of the macrolide tests, recommended procedures for parametrizing very large molecules using ffTK are given. PMID- 26280363 TI - Tissue Factor Pathway Inhibitor-Coated Stents Inhibit Restenosis in a Rabbit Carotid Artery Model. AB - INTRODUCTION: Our aim was to study the efficacy and safety of tissue factor pathway inhibitor (TFPI)-coated stents in inhibiting restenosis in a rabbit carotid artery model. METHODS: Subculture was conducted in aorta smooth muscle cell, which was taken from male Wistar rat, and the 3-5-generation cells were taken for plasmid transfection and cytotoxicity experiment. TFPI microspheres were made of a TFPI plasmid which was enwrapped by poly-l-glutamic acid (PLGA). TFPI-coated stents (n = 7) and bare metal stents (n = 6) were implanted into prepared carotid artery stenosis model of New Zealand white rabbits. The transfection efficiency of TFPI gene and its influence on animal tissue, restenosis inhibition, and biochemical indicator were observed. RESULT: Tissue factor pathway inhibitor microspheres can transfect successfully into cells, and present no cytotoxicity. Autopsy results showed no pathological changes in liver and spleen of rabbits after implanting TFPI-coated stents. TFPI gene could transfect and express successfully in vessel wall cells, and thrombus was found in some lumens of bare metal stents group after 7 day, while no such thrombus was observed in coated stents group. Degree of hyperplasia of coronary endarterectomy in bare metal stents group was evidently higher than those in coated stents group. Obvious stent restenosis was discovered only in one case in bare metal stents group (diameter stenosis >=50%). However, no case in coated stents group showed with stent restenosis. CONCLUSION: Tissue factor pathway inhibitor-coated stents could successfully transfect TFPI gene into vessel wall cells, thereby inhibiting restenosis without obvious side effect in the rabbit carotid artery model. PMID- 26280365 TI - Systematic review on the maintenance of response during systemic antipsoriatic therapy. AB - As a chronic disease psoriasis often requires long-term treatment. Successful continuation of therapy during a maintenance phase is therefore important. A systematic review was performed on the efficacy of psoriasis drugs during maintenance treatment in patients who had achieved sufficient treatment success during the induction period. Maintenance therapy is defined as treatment during the period after successful induction therapy. Inclusion criteria were prospective studies with systemic therapies recommended by the 2009 European psoriasis guidelines (plus ustekinumab), and a study population that had achieved a defined treatment response criterion after induction therapy within a period of >= 6 months. Maintenance studies on conventional treatments were identified for ciclosporin (CSA) only (no studies investigating acitretin, methotrexate or ustekinumab were found). Compared with placebo, CSA was shown to be effective in maintenance therapy, yet CSA 1.5 mg kg(-1) seems to be insufficient to maintain disease control. Based on the evidence, it is uncertain whether there is any difference between daily or intermittent treatment. For biologics, maintenance data were available for adalimumab, etanercept and infliximab. No differences in 75% improvement in Psoriasis Area and Severity Index (PASI 75) response were identified between adalimumab 40 mg once and twice a month. Continuous infliximab treatment was shown to be superior to as-needed treatment. For etanercept, only observational postrandomized controlled trial data were available, indicating a maintained PASI 75 response in approximately three-quarters of patients during long-term treatment. Only limited evidence is available for a conclusion on how patients with an adequate response should be optimally treated during the maintenance period. A clear ranking of the available treatments is not yet possible. PMID- 26280366 TI - Where Should We Eat? Lunch Source and Dietary Measures Among Youth During the School Week. AB - PURPOSE: To examine lunch sources during the school week among students and the associations with fruits and vegetable (F&V) and sugar-sweetened beverage (SSB) consumption. METHODS: Students (n = 23 680) from 43 Ontario, Canada, secondary schools completed a health behaviour survey in the Year 1 COMPASS study. Analysis used generalized linear mixed effects models. RESULTS: The most frequently reported lunch source was home (2.9 days per school week), then the school cafeteria (1.1) and fast-food places or restaurants (FFRs) (0.9). Eating a home lunch was associated with having less spending money, white ethnicity, and females; whereas cafeteria lunch was associated with more spending money, lower school grade, and females. A FFR lunch was associated with males, more spending money, and higher physical activity. Greater frequency of a home lunch was associated with greater F&V consumption. Greater frequency of a FFR lunch was associated with more frequent SSB consumption. Cafeteria lunches were associated with increases in both SSB and F&V. CONCLUSIONS: Eating a lunch obtained from outside of the home is a regular behaviour among students. Sources of school-week lunches may have an important influence on dietary intake among youth. These findings reinforce the need for strategies to promote healthier lunch sources and healthier food options. PMID- 26280364 TI - Mechanisms of Beta Cell Dysfunction Associated With Viral Infection. AB - Type 1 diabetes (T1D) results from genetic predisposition and environmental factors leading to the autoimmune destruction of pancreatic beta cells. Recently, a rapid increase in the incidence of childhood T1D has been observed worldwide; this is too fast to be explained by genetic factors alone, pointing to the spreading of environmental factors linked to the disease. Enteroviruses (EVs) are perhaps the most investigated environmental agents in relationship to the pathogenesis of T1D. While several studies point to the likelihood of such correlation, epidemiological evidence in its support is inconclusive or in some instances even against it. Hence, it is still unknown if and how EVs are involved in the development of T1D. Here we review recent findings concerning the biology of EV in beta cells and the potential implications of this knowledge for the understanding of beta cell dysfunction and autoimmune destruction in T1D. PMID- 26280367 TI - Combined Effects from gamma Radiation and Fluoranthene Exposure on Carbon Transfer from Phytoplankton to Zooplankton. AB - Risk assessment does not usually take into account mixtures of contaminants, thus potentially under- or overestimating environmental effects. We investigated how the transfer of carbon between a primary producer, Pseudokirchneriella subcapitata, and a consumer, Daphnia magna, is affected by acute exposure of gamma radiation (GR) in combination with the polycyclic aromatic hydrocarbon fluoranthene (FA). We exposed D. magna to five concentrations of FA and five acute doses of GR as single contaminants and in nine binary combinations. We compared the observed data for three end points (incorporation of carbon by D. magna, D. magna ingestion rates, and growth) to the predicted joint effects of the mixed stressors based on the independent action (IA) concept. There were deviations from the IA predictions, especially for ingestion rates and carbon incorporation by D. magna, where antagonistic effects were observed at the lower doses, while synergism was seen at the highest doses. Our results highlight the importance of investigating the effects of exposure to GR in a multistressor context. In mixtures of GR and FA, the IA-predicted effects seem to be conservative as antagonism between the two stressors was the dominant pattern, possibly due to stimulation of cellular antioxidative stress mechanisms. PMID- 26280369 TI - Occurrence, fluxes and sources of perfluoroalkyl substances with isomer analysis in the snow of northern China. AB - In this study, perfluoroalkyl substances (PFASs) and the isomers of perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) were analyzed in fresh snow samples collected from 19 cities in northern China, 2013. The levels of total PFASs in the snow samples were 33.5-229 ng/L, suggesting heavy atmospheric pollution of PFASs in northern China. PFOA (9.08-107 ng/L), PFOS (3.52-54.3 ng/L), perfluoroheptanoate (PFHpA) (3.66-44.8 ng/L), and perfluorohexanoate (PFHxA) (3.21-23.6 ng/L) were predominant with a summed contribution of 82% to the total PFASs. The particulate matters (PMs) associated PFASs contributed 21.5-56.2% to the total PFASs in the snow, suggesting PMs are vital for the transport and deposition of airborne PFASs. Partitioning of PFASs between PM and dissolved phases was dependent on the carbon chain length and end functional groups. Isomer profiles of PFOA and PFOS in the snow were in agreement with the signature of the historical 3M electrochemical fluorination (ECF) products, suggesting that the ECF products were still produced and used in China. Further source analysis showed that the airborne PFASs in urban area were mainly due to direct release rather than degradation of their precursors. PMID- 26280368 TI - Replacement of dietary soy- with air classified faba bean protein concentrate alters the hepatic transcriptome in Atlantic salmon (Salmo salar) parr. AB - The production of carnivorous fish such as Atlantic salmon (Salmo salar) is dependent on the availability of high quality proteins for feed formulations. For a number of nutritional, strategic and economic reasons, the use of plant proteins has steadily increased over the years, however a major limitation is associated with the presence of anti-nutritional factors and the nutritional profile of the protein concentrate. Investigating novel raw materials involves understanding the physiological consequences associated with the dietary inclusion of protein concentrates. The primary aim of the present study was to assess the metabolic response of salmon to increasing inclusion of air-classified faba bean protein concentrate (BPC) in feeds as a replacement for soy protein concentrate (SPC). Specifically, we tested treatments with identical contents of fishmeal (222.4gkg(-1)) and progressively higher inclusion of BPC (0gkg(-1), 111.8gkg(-1), 223.6gkg(-1), 335.4gkg(-1), 447.2gkg(-1)) substituting SPC. This study demonstrated a dose-dependent metabolic response to a plant ingredient and was the first to compare the nutrigenomic transcriptional responses after substitution of terrestrial feed ingredients such as BPC and SPC without withdrawal of marine ingredients. It was found that after eight weeks a major physiological response in liver was only evident above 335.4gkg(-1) BPC and included decreased expression of metabolic pathways, and increased expression of genes regulating transcription and translation processes and the innate immune response. Furthermore, we showed that the nutritional stress caused by BPC resembled, at least at hepatic transcriptional level, that caused by soybean meal (included as a positive control in our experimental design). The outcomes of the present study suggested that Atlantic salmon parr might efficiently utilize moderate substitution of dietary SPC with BPC, with the optimum inclusion level being around 120gkg(-1)in the type of feeds tested here. PMID- 26280370 TI - Arsenic and lead uptake by Brassicas grown on an old orchard site. AB - Arugula (Eruca sativa) and collards (Brassica oleracea var. acephala), were grown at a former orchard where soils had been variably contaminated by lead arsenate pesticides. To test for the effect of compost on As and Pb transfer into plants, compost was added (0, 5, and 10% DW) to five plots representing a wide range of soil Pb and As. Arugula accumulated about 5 times higher As concentrations in above-ground tissues than collards, with high variability in individual plant concentrations. Soil to arugula transfer (uptake) coefficients were higher for As than for Pb, and increased with soil As. Crop concentrations of Pb varied widely within replicate samples of both arugula and collards. Arugula contamination by Pb was significantly correlated to soil total Pb, but collard contamination was not. Evidence was found using Al as an indicator of soil particle contamination of plant tissues that Pb in arugula was primarily due to soil particle deposition on foliar surfaces. Compost amendments reduced 0.01 M CaCl2 -extractable Pb but increased extractable As in the orchard soils. However, compost had the beneficial effect of reducing both As and Pb concentrations in harvested arugula grown on most of the plots. PMID- 26280371 TI - Investigation on the efficiency and mechanism of Cd(II) and Pb(II) removal from aqueous solutions using MgO nanoparticles. AB - In this study, the removal of Cd(II) and Pb(II) from aqueous solutions using MgO nanoparticles prepared by a simple sol-gel method was investigated. The efficiency of Cd(II) and Pb(II) removal was examined through batch adsorption experiments. For the single adsorption of Cd(II) and Pb(II), The adsorption kinetics and isotherm data obeyed well Pseudo-second-order and Langmuir models, indicating the monolayer chemisorption of heavy metal ions. The maximum adsorption capacities calculated by Langmuir equation were 2294 mg/g for Cd(II) and 2614 mg/g for Pb(II), respectively. The adsorption process was controlled simultaneously by external mass transfer and intraparticle diffusion. In the binary system, a competitive adsorption was observed, showing preference of adsorption followed Pb(II) >Cd(II). Significantly, the elution experiments confirmed that neither Cd(II) nor Pb(II) could be greatly desorbed after water washing even for five times. XRD and XPS measurements revealed the mechanism of Cd(II) and Pb(II) removal by MgO nanoparticles was mainly involved in precipitation and adsorption on the surface of MgO, resulting from the interaction between active sites of MgO and heavy metal ions. Easy preparation, remarkable removal efficiency and firmly adsorptive ability make the MgO nanoparticles to be an efficient material in the treatment of heavy metal contaminated water. PMID- 26280372 TI - Effect of cations in the background electrolyte on the adsorption kinetics of copper and cadmium and the isoelectric point of imogolite. AB - Modification of surface charge and changes in the isoelectric point (IEP) of synthetic imogolite were studied for various cations in the background electrolyte (K(+), NH4(+), Mg(2+), and Ca(2+)). From the electrophoretic mobility data, it was established that the K(+) (KCl) concentration does not affect the IEP of imogolite; therefore, KCl is a suitable background electrolyte. In terms of the magnitude of changes in the IEP and surface charge, the cations may be ranked in the following order: Mg(2+)~Ca(2+)>>NH4(+)>>K(+). Four different kinetic models were used to evaluate the influence of Mg(2+), Ca(2+), NH4(+), and K(+) on the adsorption of Cd and Cu on synthetic imogolite. When adsorption occurs in the presence of cations with the exception of K(+), the kinetics of the process is well described by the pseudo-first order model. On the other hand, when adsorption is conducted in the presence of K(+), the adsorption kinetics is well described by the pseudo-second order, Elovich, and Weber-Morris models. From the surface charge measurements, the affinity between imogolite and the cations and their effect on the adsorption of trace elements, namely Cu and Cd, were established. PMID- 26280374 TI - Higher serum total testosterone levels correlate with increased risk of depressive symptoms in Caucasian women through the entire menopausal transition. AB - BACKGROUND: Despite the high prevalence of depressive symptoms in women, the precise role of sex hormones in mood changes during the menopausal transition is unclear. Previous studies have been inconsistent with regard to identifying the association of androgens, namely total testosterone, with depressive symptoms. OBJECTIVE: The objectives of this study were to evaluate changes in serum total testosterone levels and depressive symptoms during the entire menopausal transition, and examine the impact of covariates on the association between concurrent serum total testosterone levels and depressive symptoms during this time period. METHODS: A longitudinal cohort study (428 women at baseline with 3634 repeated measures) using data from the Penn Ovarian Aging Study, a population-based cohort of late reproductive-aged women, followed through the menopausal transition. Serum hormone parameters and depression scores using the Center for Epidemiological Studies of Depression scale (CES-D) were measured at each annual visit over a 14-year period. General linear (for testosterone) and a generalized negative-binomial model (for depressive symptoms) for repeated measures were used for analysis. RESULTS: Serum total testosterone levels increased progressively over the study period and were significantly associated with older age and with current smoking (p<0.001, respectively). In the post menopause total testosterone levels were significantly higher in African Americans compared to Caucasians (p=0.012). The proportion of women with CES-D >=16 significantly decreased with increasing age and in the post-menopausal period, and were higher in women with a history of depression and hot flashes (p<0.001). The association between concurrent testosterone levels and high depressive symptoms (CES-D >=16) differed by race (p=0.008). In Caucasians, but not African Americans, higher serum testosterone levels were associated with increased depressive symptoms after controlling for several variables including age, obesity status, hot flashes and menopausal status (RR 1.09, 95% CI 1.00 1.17, p=0.042). CONCLUSION: In our cohort, testosterone levels were low but progressively increased from premenopause through post menopause. In addition to age and history of depression, we identified race to have a significant interaction between the association of testosterone levels and depressive symptoms. This study further supports the associations between sex hormones and increased risk of having depressive symptoms, although the precise underlying mechanisms for this association remain unclear. PMID- 26280373 TI - Expression profiling of nuclear receptors in breast cancer identifies TLX as a mediator of growth and invasion in triple-negative breast cancer. AB - The Nuclear Receptor (NR) superfamily of transcription factors comprises 48 members, several of which have been implicated in breast cancer. Most important is estrogen receptor-alpha (ERalpha), which is a key therapeutic target. ERalpha action is facilitated by co-operativity with other NR and there is evidence that ERalpha function may be recapitulated by other NRs in ERalpha-negative breast cancer. In order to examine the inter-relationships between nuclear receptors, and to obtain evidence for previously unsuspected roles for any NRs, we undertook quantitative RT-PCR and bioinformatics analysis to examine their expression in breast cancer. While most NRs were expressed, bioinformatic analyses differentiated tumours into distinct prognostic groups that were validated by analyzing public microarray data sets. Although ERalpha and progesterone receptor were dominant in distinguishing prognostic groups, other NR strengthened these groups. Clustering analysis identified several family members with potential importance in breast cancer. Specifically, RORgamma is identified as being co expressed with ERalpha, whilst several NRs are preferentially expressed in ERalpha-negative disease, with TLX expression being prognostic in this subtype. Functional studies demonstrated the importance of TLX in regulating growth and invasion in ERalpha-negative breast cancer cells. PMID- 26280375 TI - Unconscious biases in task choices depend on conscious expectations. AB - Recent studies highlight the influence of non-conscious information on task-set selection. However, it has not yet been tested whether this influence depends on conscious settings, as some theoretical models propose. In a series of three experiments, we explored whether non-conscious abstract cues could bias choices between a semantic and a perceptual task. In Experiment 1, we observed a non conscious influence on task-set selection even when perceptual priming and cue target compound confounds did not apply. Experiments 2 and 3 showed that, under restrictive conditions of visibility, cues only biased task selection when the conscious task-setting mindset led participants to search for information during the time period of the cue. However, this conscious strategy did not modulate the effect found when a subjective measure of consciousness was used. Altogether, our results show that the configuration of the conscious mindset determines the potential bias of non-conscious information on task-set selection. PMID- 26280376 TI - Expand Your Horizon: A programme that improves body image and reduces self objectification by training women to focus on body functionality. AB - This study tested Expand Your Horizon, a programme designed to improve body image by training women to focus on the functionality of their body using structured writing assignments. Eighty-one women (Mage=22.77) with a negative body image were randomised to the Expand Your Horizon programme or to an active control programme. Appearance satisfaction, functionality satisfaction, body appreciation, and self-objectification were measured at pretest, posttest, and one-week follow-up. Following the intervention, participants in the Expand Your Horizon programme experienced greater appearance satisfaction, functionality satisfaction, and body appreciation, and lower levels of self-objectification, compared to participants in the control programme. Partial eta-squared effect sizes were of small to medium magnitude. This study is the first to show that focusing on body functionality can improve body image and reduce self objectification in women with a negative body image. These findings provide support for addressing body functionality in programmes designed to improve body image. PMID- 26280378 TI - Impact of residential schooling and of child abuse on substance use problem in Indigenous Peoples. AB - Residential schools were the institutions, in operation from the 19th century to the late 20th century, which Indigenous children in Canada were forced to attend. The literature shows that many young people who attended these institutions were victims of neglect and abuse. Negative psychological effects resulting from child abuse have been amply documented. However, very few studies on this subject have been carried out among Canada's Indigenous Peoples. The objective of this study is to evaluate, for an Indigenous population in Quebec (Canada), the impact of residential schooling as well as self-reported experiences of sexual and physical abuse during childhood on the development of alcohol and drug use problems in adulthood. A total of 358 Indigenous participants were interviewed (164 men [45.8%] and 194 women [54.2%]). Alcoholism was evaluated using the Michigan Alcoholism Screening Test (MAST). Drug abuse was assessed with the Drug Abuse Screening Test-20 (DAST). Child abuse and residential schooling were assessed with dichotomous questions (yes/no). Among the participants, 28.5% (n=102) had attended residential schools, 35.2% (n=121) reported having experienced sexual abuse, and 34.1% (n=117) reported having experienced physical abuse before adulthood. Results of the exact logistic regression analyses indicated that residential school attendance was linked to alcohol problems, while child abuse was related to drug use problems. The results of this study highlight the importance of considering the consequences of historical traumas related to residential schools to better understand the current situation of Indigenous Peoples in Canada. PMID- 26280377 TI - All physical activity may not be associated with a lower likelihood of adolescent smoking uptake. AB - OBJECTIVE: Research has documented that physical activity is associated with a lower risk of adolescent smoking uptake, yet it is unclear whether this relationship exists for all types of physical activity. We sought to determine whether certain types of physical activity are associated with a decreased or an increased risk of adolescent smoking uptake. METHODS: In this longitudinal cohort study, adolescents (n=1356) were surveyed every six months for four years (age 14 18years old). Smoking and physical activity were measured at each of the eight time-points. Physical activity that was negatively associated with smoking across the eight waves was considered positive physical activities (i.e., PPA; linked to not smoking such as racquet sports, running, and swimming laps). Physical activity that was positively associated with smoking across the eight waves were considered negative physical activities (i.e., NPA; linked to smoking such as skating, walking, bicycling, sport fighting, and competitive wrestling). RESULTS: Associative Processes Latent Growth Curve Modeling revealed that each 30-minute increase in NPA per week at baseline was associated with a 4-fold increased odds of smoking progression (OR=4.10, 95% CI=2.14, 7.83). By contrast, each 30-minute increase in PPA at baseline was associated with a 51% decrease in the odds of smoking progression (OR=.49, 95% CI=.25, .93). CONCLUSIONS: The type of physical activity that an adolescent engages appears to be important for the uptake of cigarette smoking among adolescents. These associative relationships warrant consideration in interventions to increase overall physical activity and those promoting physical activity to prevent smoking uptake. PMID- 26280379 TI - Cognitive and Functional Correlates of NPI-Q Scores and Symptom Clusters in Mildly Demented Alzheimer Patients. AB - Previous research has demonstrated an association between the emotional and behavioral symptoms of dementia, known as neuropsychiatric symptoms, and cognitive and functional decline among patients with Alzheimer disease (AD). The present study aimed to identify associations between neuropsychiatric symptoms as measured by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) and cognitive and functional performance. Participants were 256 AD patients enrolled in the Alzheimer's Disease and Memory Disorders Center at Baylor College of Medicine. An exploratory factor analysis of the NPI-Q indicated a 2-factor structure consisting of Negative/Oppositional and Anxiety/Restlessness factors. Regression analyses revealed significant associations between greater total severity of neuropsychiatric symptoms and poorer performance on basic and Instrumental Activities of Daily Living. Greater severity of Anxiety/Restlessness symptoms was associated with poor performance on measures of visuospatial functioning and basic and instrumental activities of daily living. The Negative/Oppositional factor was not related to cognition or functioning. In summary, neuropsychiatric symptoms (particularly Anxiety/Restlessness symptoms) were related to cognition and everyday functioning. Proper assessment and treatment of these symptoms is essential for improving cognition and functioning in AD patients. PMID- 26280381 TI - Predictive discomfort of supine humans in whole-body vibration and shock environments. AB - This work presents a predictive model to evaluate discomfort associated with supine humans during transportation, where whole-body vibration and repeated shock are predominant. The proposed model consists of two parts: (i) static discomfort resulting from body posture, joint limits and ambient discomfort; and (ii) dynamic discomfort resulting from the relative motion between the body segments as a result of transmitted vibration. Twelve supine subjects were exposed to single and 3D random vibrations and 3D shocks mixed with vibrations. The subjects' reported discomfort and biodynamic response were analysed under different support conditions, including a rigid surface, a stretcher and a stretcher with a spinal backboard. The results demonstrated good correlations between the predictive discomfort and the reported discomfort for the different conditions under consideration, with R(2) = 0.69-0.94 for individual subjects and R(2) = 0.94 for the group mean. The results also indicated a strong relationship between the head-neck and trunk angular velocities and discomfort during supine transportation. Practitioner Summary: The quantification of discomfort of supine humans under vibration and shocks by using a predictive model is an important contribution to this field, whereby the efficacy of different transport systems can be compared. The predictive discomfort model can be used as design criteria for ergonomic enhancement in supine transportation of humans. PMID- 26280380 TI - Impact of Gender-Specific Human Papillomavirus Vaccine Recommendations on Uptake of Other Adolescent Vaccines: Analysis of the NIS-Teen (2008-2012). AB - In the United States, human papillomavirus vaccination was routinely recommended for adolescent females in 2006 and provisionally recommended for adolescent males in 2009. We evaluated the hypothesis that gender-specific human papillomavirus vaccination recommendations would impact gender-specific uptake of other vaccines using National Immunization Survey-Teen public use data sets (2008-2012). Female adolescents had higher coverage than males of at least 1 other adolescent vaccine in 2008 (3.0% higher) and 2009 (4.3% higher). Gender differences abated in 2010, 2011, and 2012 (0.2%, 0.9%, and 0.4%, respectively). To evaluate unintended consequences of gender-based recommendations, countries with female-only human papillomavirus vaccination recommendations should evaluate gender-specific uptake of other adolescent vaccines. PMID- 26280382 TI - Tractography of Association Fibers Associated with Language Processing. AB - INTRODUCTION: Several major association fiber tracts are known to be part of the language processing system. There is evidence that high angular diffusion-based MRI is able to separate these fascicles in a constant way. In this study, we wanted to proof this thesis using a novel whole brain "global tracking" approach and to test for possible lateralization. METHODS: Global tracking was performed in six healthy right-handed volunteers for the arcuate fascicle (AF), the medial longitudinal fascicle (MdLF), the inferior fronto-occipital fascicle (IFOF), and the inferior longitudinal fascicle (ILF). These fiber tracts were characterized quantitatively using the number of streamlines (SL) and the mean fractional anisotropy (FA). RESULTS: We were able to characterize the AF, the MdLF, the IFOF, and the ILF consistently in six healthy volunteers using global tracking. A left-sided dominance (LI > 0.2) for the AF was found in all participants. The MdLF showed a left-sided dominance in four participants (one female, three male). Regarding the FA, no lateralization (LI > 0.2) could be shown in any of the fascicles. CONCLUSION: Using a novel global tracking algorithm we confirmed that the courses of the primary language processing associated fascicles can consistently be differentiated. Additionally we were able to show a streamline based left-sided lateralization in the AF of all right-handed healthy subjects. PMID- 26280384 TI - Age differences in experiential and deliberative processes in unambiguous and ambiguous decision making. AB - Older adults experience declines in deliberative decisional capacities, while their affective or experiential abilities tend to remain intact (Peters & Bruine de Bruin, 2012). The current study used this framework to investigate age differences in description-based and experience-based decision-making tasks. Description-based tasks emphasize deliberative processing by allowing decision makers to analyze explicit descriptions of choice-reward information. Experience based tasks emphasize affective or experiential processing because they lack the explicit choice-reward information, forcing decision makers to rely on feelings and information derived from past experiences. This study used the Columbia Card Task (CCT) as a description-based task where probability information is provided and the Iowa Gambling Task (IGT) as an experience-based task, where it is not. As predicted, compared to younger adults (N = 65), older adults (N = 65) performed more poorly on the CCT but performed similarly on the IGT. Deliberative capacities (i.e., executive control and numeracy abilities) explained the relationship between age and performance on the CCT, suggesting that age-related differences in description-based decision-making tasks are related to declines in deliberative capacities. However, deliberative capacities were not associated with performance on the IGT for either older or younger adults. Nevertheless, on the IGT, older adults reported more use of affect-based strategies versus deliberative strategies, whereas younger adults reported similar use of these strategies. This finding offers partial support for the idea that decision-making tasks that rely on deliberate processing are more likely to demonstrate age effects than those that are more experiential. PMID- 26280383 TI - The STEP model: Characterizing simultaneous time effects on practice for flight simulator performance among middle-aged and older pilots. AB - Understanding the possible effects of the number of practice sessions (practice) and time between practice sessions (interval) among middle-aged and older adults in real-world tasks has important implications for skill maintenance. Prior training and cognitive ability may impact practice and interval effects on real world tasks. In this study, we took advantage of existing practice data from 5 simulated flights among 263 middle-aged and older pilots with varying levels of flight expertise (defined by U.S. Federal Aviation Administration proficiency ratings). We developed a new Simultaneous Time Effects on Practice (STEP) model: (a) to model the simultaneous effects of practice and interval on performance of the 5 flights, and (b) to examine the effects of selected covariates (i.e., age, flight expertise, and 3 composite measures of cognitive ability). The STEP model demonstrated consistent positive practice effects, negative interval effects, and predicted covariate effects. Age negatively moderated the beneficial effects of practice. Additionally, cognitive processing speed and intraindividual variability (IIV) in processing speed moderated the benefits of practice and/or the negative influence of interval for particular flight performance measures. Expertise did not interact with practice or interval. Results indicated that practice and interval effects occur in simulated flight tasks. However, processing speed and IIV may influence these effects, even among high-functioning adults. Results have implications for the design and assessment of training interventions targeted at middle-aged and older adults for complex real-world tasks. PMID- 26280385 TI - How your executive functioning impacts me: Findings from a normative sample of older couples. AB - Although executive functioning (EF) has implications for one's emotional functioning and interpersonal behavior, and EF skills become more variable as we age, little research has investigated whether normative age-related changes in EF impact social-emotional outcomes in close others. The current study used a dyadic approach to examine the impact of individual differences in core aspects of EF on indices of well-being in 91 married or cohabiting couples aged 55 years and older. Participants in each dyad completed EF tasks of inhibition, working memory, and task switching, control tasks of language and short-term memory (STM) in which EF demands were comparatively minimal, and self-report measures of depression and quality of life. Dyadic analyses showed that individuals with lower levels of EF self-reported more depressive symptoms, though there was no significant association between an individual's EF and their partner's self reported mood. Conversely, individuals with lower levels of EF had partners who endorsed a lower quality of life, though there was no significant association between an individual's EF and their own quality of life ratings. Control tasks did not predict either aspect of well-being in either member of the dyad. Taken together, these findings highlight EF-and not simply cognition in general-as a potential determinant of well-being in oneself and one's partner among aging couples. PMID- 26280387 TI - Platinum(II) Complexes with O,S Bidentate Ligands: Biophysical Characterization, Antiproliferative Activity, and Crystallographic Evidence of Protein Binding. AB - We recently characterized a series of novel platinum(II) compounds bearing a conserved O,S binding moiety as a bifunctional ligand and evaluated their solution behavior and antiproliferative properties in vitro against a representative cancer cell line. On the whole, those platinum compounds showed an appreciable stability in mixed dimethyl sulfoxide-aqueous buffers and promising in vitro cytotoxic effects; yet they manifested a rather limited solubility in aqueous media making them poorly suitable for further pharmaceutical development. To overcome this drawback, four new derivatives of this series were prepared and characterized based on a careful choice of substituents on the O,S bidentate ligand. The solubility and stability profile of these novel compounds in a reference buffer was determined, as well as the ligands' log P(o/w) value (P(o/w) = n-octanol-water partition coefficient) as an indirect measure for the complexes' lipophilicity. The antiproliferative properties were comparatively evaluated in a panel of three cancer cell lines. The protein binding properties of the four platinum compounds were assessed using the model protein hen egg white lysozyme (HEWL), and the molecular structures of two relevant HEWL metallodrug adducts were solved. Overall, it is shown that a proper choice of the substituents leads to a higher solubility and enables a selective fine-tuning of the antiproliferative properties. The implications of these results are thoroughly discussed. PMID- 26280388 TI - Measurement Back-Action in Stacked Graphene Quantum Dots. AB - We present an electronic transport experiment in graphene where both classical and quantum mechanical charge detector back-action on a quantum dot are investigated. The device consists of two stacked graphene quantum dots separated by a thin layer of boron nitride. This device is fabricated by van der Waals stacking and is equipped with separate source and drain contacts to both dots. By applying a finite bias to one quantum dot, a current is induced in the other unbiased dot. We present an explanation of the observed measurement-induced current based on strong capacitive coupling and energy dependent tunneling barriers, breaking the spatial symmetry in the unbiased system. This is a special feature of graphene-based quantum devices. The experimental observation of transport in classically forbidden regimes is understood by considering higher order quantum mechanical back-action mechanisms. PMID- 26280386 TI - Novel Pyrazolo[1,5-a]pyrimidines as Translocator Protein 18 kDa (TSPO) Ligands: Synthesis, in Vitro Biological Evaluation, [(18)F]-Labeling, and in Vivo Neuroinflammation PET Images. AB - A series of novel pyrazolo[1,5-a]pyrimidines, closely related to N,N-diethyl-2-(2 (4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide (2, DPA-714), were synthesized and biologically in vitro evaluated for their potential to bind the translocator protein 18 kDa (TSPO), a protein today recognized as an early biomarker of neuroinflammatory processes. This series is composed of fluoroalkyl- and fluoroalkynyl- analogues, prepared from a common iodinated intermediate via Sonogashira coupling reactions. All derivatives displayed subnanomolar affinity for the TSPO (0.37 to 0.86 nM), comparable to that of 2 (0.91 nM). Two of them were radiolabeled with fluorine-18, and their biodistribution was investigated by in vitro autoradiography and positron emission tomography (PET) imaging on a rodent model of neuroinflammation. Brain uptake and local accumulation of both compounds in the AMPA-mediated lesion confirm their potential as in vivo PET-radiotracers. In particular, [(18)F]23 exhibited a significantly higher ipsi- to contralateral ratio at 60 min than the parent molecule [(18)F]2 in vivo. PMID- 26280389 TI - Asia-Pacific women's experiences of stillbirth: A metasynthesis of qualitative literature. AB - Literature related to Asia-Pacific women's lived experiences of stillbirth was reviewed through metasynthesis of selected empirical studies. An overarching construct of "interconnectedness" between complex experiences influenced by cultural and systemic factors became apparent. Four experiential themes emerged: "acts of accusation," "rocky relationships," "entangled emotions," and "routines of reconciliation." These were influenced by two systemic factors: "contexts of culture" and "health care matters." Women's sociocultural experiences and their engagement with health care systems influenced how they managed and reconciled their loss. This study contributes to the literature on women's experiences of stillbirth, furthering theory creation and generating future research agendas. PMID- 26280390 TI - Chronic Disease and Chemical Dependency Treatment in Primary Care Patients With Problem Drug Use. AB - This article examines whether chronic disease is associated with chemical dependency treatment in primary care patients with problem drug use. Chronic disease was common in 781 disadvantaged individuals who had problem drug use and were seen in primary care clinics affiliated with a public safety-net hospital. Individuals had, on average, 5.4 chronic medical conditions, and overall 57% had low severity chronic disease. In the year following enrollment, 14% had chemical dependency treatment. Severity of chronic disease was not associated with chemical dependency treatment (p = .26). In summary, chronic disease neither hindered chemical dependency treatment, nor did it facilitate such treatment. PMID- 26280392 TI - Lead removal by Spirulina platensis biomass. AB - In this investigation, we report on the biosorption of Pb (II) from aqueous solutions by the nonliving biomass of the micro-alga (cyanobacterium) Spirulina platensis. Propagation of the micro-alga was carried out in outside oblong raceway ponds. The biomass was cleaned, dried and used for the investigation. The effects of pH, adsorbent dose, temperature, initial concentration of Pb (II), and contact time on the adsorption of lead by the dry biomass were studied. The experiments were carried out in 250 ml conical flasks containing 100 ml of test solutions using an orbital incubator at 150 rpm. Concentrations of the metal before and after the experiments were measured using Atomic Absorption Spectrophotometer. Very high levels of Pb (II) removal (>91%) were obtained. The optimum conditions for maximal adsorption by S. platensis were found to be pH 3; 2 g of adsorbent dose; incubation at 26 degrees C; 100 mg/l of lead initial concentration and 60 minutes of contact time. The experimental data fitted well with Freundlich isotherm equation with R(2) values greater than 0.97. Based on our results, we recommend the utilization of S. platensis biomass for heavy metal removal from aqueous solutions. PMID- 26280391 TI - Principles of protein targeting to the nucleolus. AB - The nucleolus is the hallmark of nuclear compartmentalization and has been shown to exert multiple roles in cellular metabolism besides its main function as the place of rRNA synthesis and assembly of ribosomes. Nucleolar proteins dynamically localize and accumulate in this nuclear compartment relative to the surrounding nucleoplasm. In this study, we have assessed the molecular requirements that are necessary and sufficient for the localization and accumulation of peptides and proteins inside the nucleoli of living cells. The data showed that positively charged peptide entities composed of arginines alone and with an isoelectric point at and above 12.6 are necessary and sufficient for mediating significant nucleolar accumulation. A threshold of 6 arginines is necessary for peptides to accumulate in nucleoli, but already 4 arginines are sufficient when fused within 15 amino acid residues of a nuclear localization signal of a protein. Using a pH sensitive dye, we found that the nucleolar compartment is particularly acidic when compared to the surrounding nucleoplasm and, hence, provides the ideal electrochemical environment to bind poly-arginine containing proteins. In fact, we found that oligo-arginine peptides and GFP fusions bind RNA in vitro. Consistent with RNA being the main binding partner for arginines in the nucleolus, we found that the same principles apply to cells from insects to man, indicating that this mechanism is highly conserved throughout evolution. PMID- 26280393 TI - Discovering functional, non-proteinogenic amino acid containing, peptides using genetic code reprogramming. AB - The protein synthesis machinery of the cell, the ribosome and associated factors, is able to accurately follow the canonical genetic code, that which maps RNA sequence to protein sequence, to assemble functional proteins from the twenty or so proteinogenic amino acids. A number of innovative methods have arisen to take advantage of this accurate, and efficient, machinery to direct the assembly of non-proteinogenic amino acids. We review and compare these routes to 'reprogram the genetic code' including in vitro translation, engineered aminoacyl tRNA synthetases, and RNA 'flexizymes'. These studies show that the ribosome is highly tolerant of unnatural amino acids, with hundreds of unusual substrates of varying structure and chemistries being incorporated into protein chains. We also discuss how these methods have been coupled to selection techniques, such as phage display and mRNA display, opening up an exciting new avenue for the production of proteins and peptides with properties and functions beyond that which is possible using proteins composed entirely of the proteinogenic amino acids. PMID- 26280394 TI - Progress towards high-power Li/CFx batteries: electrode architectures using carbon nanotubes with CFx. AB - Carbon monofluoride (CFx) has a high energy density, exceeding 2000 W h kg(-1), yet its application in primary lithium batteries is limited by its power capability. Multi-walled carbon nanotubes (CNTs) are appealing additives for high power batteries, due to their outstanding electronic transport properties, high aspect ratio necessitating low volume fraction for percolation, and high tensile strength. This perspective describes the current state of the art in lithium carbon monofluoride (Li/CFx) batteries and highlights the opportunities for the development of high-power Li/CFx batteries via utilization of carbon nanotubes. In this report, we generated several electrode architectures using CFx/CNT combinations, and demonstrated the effectiveness of CNTs in enhancing the rate capability and energy density of Li/CFx batteries. First, we investigated the resistivity of CFx combined with CNTs and compared the CFx/CNT composites with conventional carbon additives. Second, we built CFx-CNT electrodes without metallic current collectors using CNTs as substrates, and compared their electrochemical performance with conventional CFx electrodes using aluminum foil as a current collector. Furthermore, we fabricated multi-layered CNT-CFx-CNT composite electrodes (sandwich electrodes) and studied the impact of the structure on the performance of the electrode. Our work demonstrates some of the opportunities for utilization of CNTs in CFx electrodes and the resultant implementation of CFx as a battery cathode in next-generation high-power batteries. PMID- 26280395 TI - Liposomal cytarabine in prophylaxis or curative treatment of central nervous system involvement in Burkitt leukemia/lymphoma. AB - In recent years, the outcome of Burkitt leukemia/lymphoma (BL) has improved significantly. Central nervous system (CNS) involvement continues to be a poor prognostic indicator. High doses of intravenous polychemotherapy, intrathecal chemotherapy, and cranio-spinal radiation therapy are used by numerous groups. Majority of patients are cured after this strategy. The next challenge is to decrease toxicities of treatment, including long-term toxicities secondary to cranio-spinal radiation therapy observed in these cured patients. Liposomal cytarabine could be a good alternative to cranio-spinal radiation therapy as already reported in acute lymphoblastic leukemia. We report here eleven patients treated in our center for BL, with liposomal cytarabine instead of cranio-spinal radiation therapy as prophylactic or curative treatment for CNS involvement. Treatment was safe with no short-term grade >3 adverse events. Moreover, no long term side effects and no impact on outcome were observed. We conclude that LC could be a good option to decrease short/long-term side effects of cranio-spinal radiation therapy in BL and could be evaluated in a future clinical trial. PMID- 26280396 TI - Effects of Ni stress on the uptake and translocation of Ni and other mineral nutrition elements in mature wheat grown in sierozems from northwest of China. AB - Effects of heavy metal on uptake of mineral nutrition elements in plants have attracted widespread interest and been widely explored. This paper reports the translocation and accumulation behaviors of Ni in the organs of mature wheat plants by means of pot experiment using the sierozem collected from northwestern China as experimental soil. Effect of Ni on accumulation of Cu, Mn, Ca, and Mg is also demonstrated. It was found that influence of Ni on wheat plants differed greatly at different Ni levels. Ni content in the organs of wheat plants increased with the increase in Ni level, and the increasing rate decreased when the Ni level was higher than 400 mg/kg. Ni was mainly accumulated in the roots and less distributed in the shoots, shells, and grains. When the Ni level was lower than 400 mg/kg, the bioconcentration factor (BCF) of the roots was higher than 1, suggesting that Ni was taken in against a concentration gradient. The average translocation factor (TF) of wheat plants was 0.221, indicating the weak ability of wheat plants in translocating Ni toward the aboveground parts. Since Ni is readily accumulated in the grains of wheat plants at lower Ni level, concerns in health risks might be raised. Excess Ni in wheat plants could inhibit the transfer of Cu, Mn, and Mg to grains, leading to the accumulation of Ca, Mg, and Mn in the shoots and shells of wheat plants. The increase in Ni content can disturb the uptake and distribution of mineral nutrition elements in the organs of plants, resulting in the toxic effect of Ni on wheat plants. Results from this study provide a scientific support to prevent or control heavy metal pollution in an arid region. PMID- 26280399 TI - Antibacterial effects and action modes of asiatic acid. AB - In this study, the antibacterial effects and action modes of asiatic acid against the foodborne bacterial pathogens Escherichia coli O157:H7, Salmonella Typhimurium DT104, Pseudomonas aeruginosa, Listeria monocytogenes, Staphylococcus aureus, Enterococcus faecalis, and Bacillus cereus were examined. Minimal inhibitory concentrations (MICs) of asiatic acid against these bacteria were in the range of 20-40 MUg/mL. Minimum bactericidal concentrations of asiatic acid were in the range of 32-52 MUg/mL. Asiatic acid at 2X MIC effectively reduced bacterial numbers from 6 log10 to < 2 log10 in all test bacteria within 6 h (P < 0.05). The antibacterial activity of asiatic acid was not affected by heat treatments from 25 to 100 degrees C. Asiatic acid at 1 or 2X MICs caused 40-56% and 71-89% membrane damage in test bacteria within 2 h, respectively In addition, asiatic acid at 1 or 2X MICs led to 1.5-2.4 ppm and 2.9-4.1 ppm K(+) release within 2 hr, respectively. Asiatic acid treatments dose-dependently increased bacterial nucleotide leakage (P < 0.05). After 3 days of storage at 25 degrees C, the addition of asiatic acid dose-dependently inhibited the growth of test bacteria in ground beef (P < 0.05), in which 8 mg asiatic acid treatments led to bacterial levels (log CFU/g) in said ground beef lower than 2. These findings suggest that asiatic acid might be a potent antibacterial agent to prevent food contamination. PMID- 26280398 TI - Using gastric juice lncRNA-ABHD11-AS1 as a novel type of biomarker in the screening of gastric cancer. AB - Long noncoding RNAs (lncRNAs) play vital roles in tumorigenesis. However, the diagnostic values of most lncRNAs are largely unknown. To investigate whether gastric juice lncRNA-ABHD11-AS1 can be a potential biomarker in the screening of gastric cancer, 173 tissue samples and 130 gastric juice from benign lesion, gastric dysplasia, gastric premalignant lesions, and gastric cancer were collected. ABHD11-AS1 levels were detected by reverse transcription-polymerase chain reaction. Then, the relationships between ABHD11-AS1 levels and clinicopathological factors of patients with gastric cancer were investigated. The results showed that ABHD11-AS1 levels in gastric cancer tissues were significantly higher than those in other tissues. Its levels in gastric juice from gastric cancer patients were not only significantly higher than those from cases of normal mucosa or minimal gastritis, atrophic gastritis, and gastric ulcers but also associated with gender, tumor size, tumor stage, Lauren type, and blood carcinoembryonic antigen (CEA) levels. More importantly, when using gastric juice ABHD11-AS1 as a marker, the positive detection rate of early gastric cancer patients was reached to 71.4 %. Thanks to the special origin of gastric juice, these results indicate that gastric juice ABHD11-AS1 may be a potential biomarker in the screening of gastric cancer. PMID- 26280397 TI - Pharmacological Inhibition of Protein Lipidation. AB - Lipid modifications of mammalian proteins are widespread, modifying thousands of targets involved in all aspects of cellular physiology cellular physiology. Broadly, lipidations serve to increase protein hydrophobicity and association with cellular membranes. Often, these modifications are absolutely essential for protein stability and localization, and serve critical roles in dynamic regulation of protein function. A number of lipidated proteins are associated with diseases, including parasite infections, neurological diseases, diabetes, and cancer, suggesting that lipid modifications represent potentially attractive targets for pharmacological intervention. This review briefly describes the various types of posttranslational protein lipid modifications, proteins modified by them, and the enzymatic machinery associated with these. We then discuss several case studies demonstrating successful development of lipidation inhibitors of potential (and more rarely, realized) clinical value. Although this field remains in its infancy, we believe these examples demonstrate the potential utility of targeting protein lipidation as a viable strategy for inhibiting the function of pathogenic proteins. PMID- 26280400 TI - Developmental Trajectories of Youth Character: A Five-Wave Longitudinal Study of Cub Scouts and Non-Scout Boys. AB - Youth development programs, such as the Boy Scouts of America, aim to develop positive attributes in youth (e.g., character virtues, prosocial behaviors, and positive civic actions), which are necessary for individuals and societies to flourish. However, few developmental studies have focused on how specific positive attributes develop through participation in programs such as the Boy Scouts of America. As part of the Character and Merit Project, this article examined the developmental trajectories of character and other positive attributes, which are of focal concern of the Boy Scouts of America and the developmental literature. Data were collected from 1398 Scouts (M = 8.59 years, SD = 1.29 years, Range 6.17-11.92 years) and 325 non-Scout boys (M = 9.06 years, SD = 1.43 years, Range 6.20-11.81 years) over five waves of testing across a two and-half-year period. Latent growth-curve analyses of self-report survey data examined the developmental trajectories of the attributes. Older youth rated themselves lower than younger participants on helpfulness, reverence, thriftiness, and school performance. However, all youth had moderately high self ratings on all the attributes. Across waves, Scouts' self-ratings increased significantly for cheerfulness, helpfulness, kindness, obedience, trustworthiness, and hopeful future expectations. Non-Scout boys' self-ratings showed no significant change for any attributes except for a significant decrease in religious reverence among non-Scout boys from religious institutions. We discuss implications for positive youth development and for the role of the Boy Scouts of America programming in character development. PMID- 26280402 TI - Evidence-based recommendations of postoperative radiotherapy in lung cancer from Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society). AB - Locally advanced non-small cell lung cancer (NSCLC) is a diversified illness in which postoperative radiation therapy (PORT) for complete resection with positive hiliar (pN1) and/or mediastinal (pN2) lymph nodes is controversial. Although several studies have shown that PORT has beneficial effects, randomized trials are needed to demonstrate its impact on overall survival. In this review, the Spanish Radiation Oncology Group for Lung Cancer describes the most relevant literature on PORT in NSCLC patients stage pN1-2. In addition, we have outlined the current recommendations of different national and international clinical guidelines and have also specified practical issues regarding treatment volume definition, doses and fractionation. PMID- 26280401 TI - Predictors of Age of Diagnosis for Children with Autism Spectrum Disorder: The Role of a Consistent Source of Medical Care, Race, and Condition Severity. AB - Having a consistent source of medical care may facilitate diagnosis of autism spectrum disorders (ASD). This study examined predictors of age of ASD diagnosis using data from the 2011-2012 National Survey of Children's Health. Using multiple linear regression analysis, age of diagnosis was predicted by race, ASD severity, having a consistent source of care (CSC), and the interaction between these variables after controlling for birth cohort, birth order, poverty level, parental education, and health insurance. While African American children were diagnosed earlier than Caucasians, this effect was moderated by ASD severity and CSC. Having a CSC predicted earlier diagnosis for Caucasian but not African American children. Both physician and parent behaviors may contribute to diagnostic delays in minority children. PMID- 26280403 TI - Role of SPECT-CT in breast cancer sentinel node biopsy when internal mammary chain drainage is observed. AB - INTRODUCTION: SPECT-CT in the detection of the sentinel lymph node (SLN) of breast cancer offers known advantages over conventional planar lymphoscintigraphy. Sometimes, it shows atypical findings like mediastinal lymphatic drainage. We have evaluated these atypical findings showed by SPECT-CT performed in patients with migration to the internal mammary chain (IMC) and their roles in the management of the patients. MATERIALS AND METHODS: We reviewed the 56 lymphoscintigraphies (planar and SPECT-CT) of 56 women (average age: 55 years) diagnosed with breast cancer with IMC migration observed in the planar images. We compared the two techniques, obtaining the number of depicted nodes, atypical locations, their exact anatomical location and their role in the management of the patient. RESULTS: Planar images showed a total number of 81 IMC nodes. SPECT-CT showed 74 nodes in the IMC territory and 14 mediastinal lymphatic nodes in 6 patients. Out of the 81 IMC nodes reported by planar images, seven corresponded to mediastinal nodes. Planar and hybrid images showed 110 and 130 axillary nodes, respectively. SPECT-CT showed additional findings in five patients: three infraclavicular and two supraclavicular nodes that were exactly located. One intramammary node was discarded by the SPECT-CT as a focal skin contamination. CONCLUSION: Mediastinal nodes are unexpected, but not uncommon findings that are important in the planning of SLN biopsy. SPECT-CT found more nodes than planar images, being able to separate mediastinal and IMC nodes, helping to exactly depict the SLN and its relations with anatomical structures. PMID- 26280405 TI - Objective Measurement of Cough Frequency During COPD Exacerbation Convalescence. AB - Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Cough and sputum production are associated with adverse outcomes in COPD and are common during COPD exacerbation (AE-COPD). This study of objective cough monitoring using the Hull Automated Cough Counter and Leicester Cough Monitor software confirms that this system has the ability to detect a significant decrease in cough frequency during AE-COPD convalescence. The ability to detect clinically meaningful change indicates a potential role in home monitoring of COPD patients. PMID- 26280404 TI - Reversal of muscle atrophy by Zhimu and Huangbai herb pair via activation of IGF 1/Akt and autophagy signal in cancer cachexia. AB - PURPOSE: Muscle atrophy is the prominent clinical feature of cancer-induced cachexia. Zhimu and Huangbai herb pair (ZBHP) has been used since ancient China times and have been phytochemically investigated for constituents that might cause anti-cancer, diabetes, and their complication. In this study, the effects and mechanisms of ZBHP on reversal of muscle atrophy were explored. METHODS: C57BL/6 mice implanted with colon-26 adenocarcinoma were chosen to develop cancer cachexia for evaluating the effects of ZBHP on reversal of muscle atrophy. The body weight, survival time, inflammatory cytokines, and pathological changes of muscle were monitored. In addition, IGF-1/Akt and autophagy pathway members were analyzed to interpret the mechanism of drug response. RESULTS: The function and morphology of skeletal muscle in cachexia model were significantly disturbed, and the survival time was shortened. Consistently, inflammatory cytokines and muscle atrophy-related atrogin-1, MuRF1, and FOXO3 were significantly increased, and IGF 1/Akt and autophagy signal pathways were depressed. Treatment with ZBHP significantly alleviated tumor-free body weight reduction and cachexia-induced changes in cytokines and prolonged survival. ZBHP treatment not only inhibited the muscle atrophy-related genes but also activated the IGF-1/Akt and autophagy signal pathways to facilitate the protein synthesis. CONCLUSIONS: The results revealed that ZBHP treatment could inhibit the muscle atrophy induced by cancer cachexia and prolong the survival time, and ZBHP may be of value as a pharmacological alternative in treatment of cancer cachexia. PMID- 26280406 TI - Biosensors: Microcantilevers to lift biomolecules. PMID- 26280407 TI - Three-terminal energy harvester with coupled quantum dots. AB - Rectification of thermal fluctuations in mesoscopic conductors is the key idea behind recent attempts to build nanoscale thermoelectric energy harvesters to convert heat into useful electric power. So far, most concepts have made use of the Seebeck effect in a two-terminal geometry, where heat and charge are both carried by the same particles. Here, we experimentally demonstrate the working principle of a new kind of energy harvester, proposed recently, using two capacitively coupled quantum dots. We show that, due to the novel three-terminal design of our device, which spatially separates the heat reservoir from the conductor circuit, the directions of charge and heat flow become decoupled. This enables us to manipulate the direction of the generated charge current by means of external gate voltages while leaving the direction of heat flow unaffected. Our results pave the way for a new generation of multi-terminal nanoscale heat engines. PMID- 26280408 TI - Information storage and retrieval in a single levitating colloidal particle. AB - The binary switch is a basic component of digital information. From phase-change alloys to nanomechanical beams, molecules and atoms, new strategies for controlled bistability hold great interest for emerging technologies. We present a generic methodology for precise and parallel spatiotemporal control of nanometre-scale matter in a fluid, and demonstrate the ability to attain digital functionalities such as switching, gating and data storage in a single colloid, with further implications for signal amplification and logic operations. This fluid-phase bit can be arrayed at high densities, manipulated by either electrical or optical fields, supports low-energy, high-speed operation and marks a first step toward 'colloidal information'. The principle generalizes to any system where spatial perturbation of a particle elicits a differential response amenable to readout. PMID- 26280409 TI - Decoupling competing surface binding kinetics and reconfiguration of receptor footprint for ultrasensitive stress assays. AB - Cantilever arrays have been used to monitor biochemical interactions and their associated stress. However, it is often necessary to passivate the underside of the cantilever to prevent unwanted ligand adsorption, and this process requires tedious optimization. Here, we show a way to immobilize membrane receptors on nanomechanical cantilevers so that they can function without passivating the underlying surface. Using equilibrium theory, we quantitatively describe the mechanical responses of vancomycin, human immunodeficiency virus type 1 antigens and coagulation factor VIII captured on the cantilever in the presence of competing stresses from the top and bottom cantilever surfaces. We show that the area per receptor molecule on the cantilever surface influences ligand-receptor binding and plays an important role on stress. Our results offer a new way to sense biomolecules and will aid in the creation of ultrasensitive biosensors. PMID- 26280410 TI - Effect of Early Adversity and Childhood Internalizing Symptoms on Brain Structure in Young Men. AB - IMPORTANCE: Early adversity is an important risk factor that relates to internalizing symptoms and altered brain structure. OBJECTIVE: To assess the direct effects of early adversity and child internalizing symptoms (ie, depression, anxiety) on cortical gray matter (GM) volume, as well as the extent to which early adversity associates with variation in cortical GM volume indirectly via increased levels of internalizing symptoms. DESIGN, SETTING, AND PARTICIPANTS: A prospective investigation of associations between adversity within the first 6 years of life, internalizing symptoms during childhood and early adolescence, and altered brain structure in late adolescence (age, 18-21 years) was conducted in a community-based birth cohort in England (Avon Longitudinal Study of Parents and Children). Participants from the cohort included 494 mother-son pairs monitored since the mothers were pregnant (estimated date of delivery between April 1, 1991, and December 31, 1992). Data collection for the present study was conducted between April 1, 1991, and November 30, 2010; the neuroimaging data were collected between September 1, 2010, and November 30, 2012, and data analyses for the present study occurred between January 25, 2013, and February 15, 2015. Risk factors were adversity within the first 6 years of the child's life (including prenatal exposure) and the child's internalizing symptoms between age 7 and 13 years. EXPOSURES: Early childhood adversity. MAIN OUTCOMES AND MEASURES: The main outcome was GM volume of cortical regions previously associated with major depression measured through T1-weighted magnetic resonance images collected in late adolescence. RESULTS: Among 494 young men included in this analysis, early adversity was directly associated with lower GM volumes in the anterior cingulate cortex (beta = -.18; P = .01) and higher GM volume in the precuneus (beta = .18; P = .009). Childhood internalizing symptoms were associated with lower GM volume in the right superior frontal gyrus (beta = -.20; P = .002). Early adversity was also associated with higher levels of internalizing symptoms (beta = .37; P < .001), which, in turn, were associated with lower superior frontal gyrus volume (ie, an indirect effect) (beta = -.08; 95% CI, -0.14 to -0.01; P = .02). CONCLUSIONS AND RELEVANCE: Adversity early in life was associated with higher levels of internalizing symptoms as well as with altered brain structure. Early adversity was related to variation in brain structure both directly and via increased levels of internalizing symptoms. These findings may suggest that some of the structural variation often attributed to depression might be associated with early adversity in addition to the effect of depression. PMID- 26280411 TI - Massively parallel high-order combinatorial genetics in human cells. AB - The systematic functional analysis of combinatorial genetics has been limited by the throughput that can be achieved and the order of complexity that can be studied. To enable massively parallel characterization of genetic combinations in human cells, we developed a technology for rapid, scalable assembly of high-order barcoded combinatorial genetic libraries that can be quantified with high throughput sequencing. We applied this technology, combinatorial genetics en masse (CombiGEM), to create high-coverage libraries of 1,521 two-wise and 51,770 three-wise barcoded combinations of 39 human microRNA (miRNA) precursors. We identified miRNA combinations that synergistically sensitize drug-resistant cancer cells to chemotherapy and/or inhibit cancer cell proliferation, providing insights into complex miRNA networks. More broadly, our method will enable high throughput profiling of multifactorial genetic combinations that regulate phenotypes of relevance to biomedicine, biotechnology and basic science. PMID- 26280412 TI - High-throughput phosphoproteomics reveals in vivo insulin signaling dynamics. AB - Mass spectrometry has enabled the study of cellular signaling on a systems-wide scale, through the quantification of post-translational modifications, such as protein phosphorylation. Here we describe EasyPhos, a scalable phosphoproteomics platform that now allows rapid quantification of hundreds of phosphoproteomes in diverse cells and tissues at a depth of >10,000 sites. We apply this technology to generate time-resolved maps of insulin signaling in the mouse liver. Our results reveal that insulin affects ~10% of the liver phosphoproteome and that many known functional phosphorylation sites, and an even larger number of unknown sites, are modified at very early time points (<15 s after insulin delivery). Our kinetic data suggest that the flow of signaling information from the cell surface to the nucleus can occur on very rapid timescales of less than 1 min in vivo. EasyPhos facilitates high-throughput phosphoproteomics studies, which should improve our understanding of dynamic cell signaling networks and how they are regulated and dysregulated in disease. PMID- 26280414 TI - Treatment of blood cholesterol to reduce risk for atherosclerotic cardiovascular disease: grand rounds discussion from the beth Israel Deaconess Medical Center. AB - In November 2013, the American College of Cardiology and the American Heart Association released a clinical practice guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease (ASCVD) risk in adults. The recommendation identifies 4 patient groups with strong evidence that the benefits of reduction in ASCVD events from statin therapy exceed adverse events. For these patients, initiating statin therapy of an appropriate intensity to reduce ASCVD risk and minimize adverse effects is recommended. A new risk estimator based on a pooled cohort equation is presented for estimating 10-year ASCVD risk. There is also a recommendation to engage in a clinician-patient discussion before initiating a statin, especially for primary prevention of ASCVD. This paper summarizes a discussion between a cardiologist and an internist about how each clinician would balance these factors and what treatment they would suggest for an individual patient. PMID- 26280413 TI - Overexpression of receptor-like kinase ERECTA improves thermotolerance in rice and tomato. AB - The detrimental effects of global warming on crop productivity threaten to reduce the world's food supply. Although plant responses to changes in temperature have been studied, genetic modification of crops to improve thermotolerance has had little success to date. Here we demonstrate that overexpression of the Arabidopsis thaliana receptor-like kinase ERECTA (ER) in Arabidopsis, rice and tomato confers thermotolerance independent of water loss and that Arabidopsis er mutants are hypersensitive to heat. A loss-of-function mutation of a rice ER homolog and reduced expression of a tomato ER allele decreased thermotolerance of both species. Transgenic tomato and rice lines overexpressing Arabidopsis ER showed improved heat tolerance in the greenhouse and in field tests at multiple locations in China during several seasons. Moreover, ER-overexpressing transgenic Arabidopsis, tomato and rice plants had increased biomass. Our findings could contribute to engineering or breeding thermotolerant crops with no growth penalty. PMID- 26280417 TI - Aggressive case finding: a clinical strategy for the documentation of thyroid dysfunction. PMID- 26280418 TI - Celebrating the ACP centennial: from the annals archive-non-A, non-B hepatitis. PMID- 26280419 TI - On being a doctor: shining a light on the dark side. PMID- 26280420 TI - Our family secrets. PMID- 26280421 TI - Type 2 diabetes. PMID- 26280422 TI - Type 2 diabetes. PMID- 26280423 TI - Firearm-related injury and death in the United States. PMID- 26280424 TI - Firearm-related injury and death in the United States. PMID- 26280425 TI - Firearm-related injury and death in the United States. PMID- 26280426 TI - Firearm-related injury and death in the United States. PMID- 26280427 TI - Reducing firearm-related harms. PMID- 26280428 TI - Reducing firearm-related harms. PMID- 26280429 TI - What should we regard as an "elevated" C-reactive protein level? PMID- 26280430 TI - Insurance plan presentation and decision support on HealthCare.gov and state based web sites created for the Affordable Care Act. PMID- 26280431 TI - Web Exclusives. The consult guys - shoot from the hip? surgery with aortic stenosis. PMID- 26280432 TI - ACP Journal Club: in early septic shock, early goal-directed therapy did not reduce 90-day mortality. PMID- 26280433 TI - ACP Journal Club: anatomical and functional testing did not differ for reducing CV events in suspected obstructive CAD. PMID- 26280434 TI - ACP Journal Club: baseline plus 1-hour high-sensitivity cardiac troponin T improved early rule-out and rule-in of acute MI. PMID- 26280435 TI - ACP Journal Club: in hospital rehabilitation units, adding individualized fall prevention education to usual care reduced falls. PMID- 26280436 TI - ACP Journal Club: review: ambulatory blood pressure monitoring predicts cardiovascular events. PMID- 26280437 TI - ACP Journal Club: David Lawrence Sackett, MD, MSc (Epidemiology), 1934-2015. PMID- 26280438 TI - ACP Journal Club: transcatheter and surgical aortic valve replacement did not differ for mortality in severe aortic stenosis. PMID- 26280439 TI - ACP Journal Club: transcatheter aortic valve replacement reduced mortality more than usual care in inoperable severe aortic stenosis. PMID- 26280440 TI - ACP Journal Club: adding neurovascular thrombectomy to IV t-PA reduced disability in acute ischemic stroke. PMID- 26280441 TI - ACP Journal Club: review: in lacunar stroke, single antiplatelet therapy reduces recurrent stroke more than placebo. PMID- 26280442 TI - ACP Journal Club: in palliative care, discontinuation of statins did not differ from continuation for mortality. PMID- 26280443 TI - ACP Journal Club: review: some commercial or proprietary weight-loss programs increase weight loss. PMID- 26280444 TI - ACP Journal Club: combination intensive DMARD therapy is noninferior to TNF inhibitors for reducing disability in active RA. PMID- 26280445 TI - Synthesis of Allenyl Sulfones via a TBHP/TBAI-Mediated Reaction of Propargyl Alcohols with Sulfonyl Hydrazides. AB - A new TBHP/TBAI-mediated reaction of propargyl alcohols with sulfonyl hydrazides in the presence of HOAc has been established, in which a wide variety of allenyl sulfones were obtained in moderate to excellent yields. Mechanistic studies indicate that this transformation involves HOAc-promoted sulfonohydrazide intermediate formation, sequential C-O, C-N, and N-S bond cleavage, and C-S bond formation. Significantly, this sulfonohylation proceeds in a radical process and shows highly functional group compatibility and excellent regioselectivity, with a short reaction time and inexpensive reagents. PMID- 26280446 TI - Modelling mesoporous alumina microstructure with 3D random models of platelets. AB - This work focuses on a mesoporous material made up of nanometric alumina 'platelets' of unknown shape. We develope a 3D random microstructure to model the porous material, based on 2D transmission electron microscopy (TEM) images, without prior knowledge on the spatial distribution of alumina inside the material. The TEM images, acquired on samples with thickness 300 nm, a scale much larger than the platelets's size, are too blurry and noisy to allow one to distinguish platelets or platelets aggregates individually. In a first step, the TEM images correlation function and integral range are estimated. The presence of long-range fluctuations, due to the TEM inhomogeneous detection, is detected and corrected by filtering. The corrected correlation function is used as a morphological descriptor for the model. After testing a Boolean model of platelets, a two-scale model of microstructure is introduced to replicate the statistical dispersion of platelets observed on TEM images. Accordingly, a set of two-scale Boolean models with varying physically admissible platelets shapes is proposed. Upon optimization, the model takes into account the dispersion of platelets in the microstructure as observed on TEM images. Comparing it to X-ray diffraction and nitrogen porosimetry data, the model is found to be in good agreement with the material in terms of specific surface area. PMID- 26280447 TI - LCZ696 (Valsartan/Sacubitril)--A Possible New Treatment for Hypertension and Heart Failure. AB - The aim of this MiniReview was to introduce the newly invented dual-acting drug valsartan/sacubitril (LCZ696), which combines an angiotensin receptor blocker (valsartan) with sacubitril, a specific inhibitor of the neutral endopeptidase (NEP) that degrades vasoactive peptides, including natriuretic peptides ANP and BNP, but also glucagon, enkephalins and bradykinin, among others. The MiniReview presents the data of four available trials NCT01193101, NCT00549770, NCT00887588 and NCT01035255 and provides the current knowledge about LCZ696 effects in patients with hypertension and heart failure. Presently, patients suffering from hypertension and heart failure are treated with ACE inhibitors or angiotensin receptor antagonists often in combination with other drugs. These current medications lead to a reduction in blood pressure in hypertensive patients and a decreased mortality and morbidity in patients with heart failure with reduced ejection fraction, but not in patients with heart failure with preserved ejection fraction. LCZ696 had been tested to utilize the beneficial properties of natriuretic peptides in combination with angiotensin receptor antagonism. It induces even greater blood pressure reductions and decreased mortality and morbidity in patients with heart failure with reduced ejection fraction, while patients with heart failure with preserved ejection fraction show lowered blood pressure and decreased NT-pro-BNP levels. Although long-term studies remain to be performed, these initial data suggest that there is a potential clinical benefit of LCZ696 in the treatment of hypertension and heart failure. PMID- 26280448 TI - Fabrication of Polystyrene/ZnO Micronano Hierarchical Structure Applied for Light Extraction of Light-Emitting Devices. AB - Polystyrene(PS)/ZnO micronano hierarchical structures were fabricated on a flat surface by depositing ZnO nanoparticles from a cluster beam at oblique incidence on the surface predeposited with PS microspheres. The hierarchical structure was composed of submicron-sized PS particle layers covered with dense films of columnar ZnO nanoparticle piles separated with nanoscale pores. It was demonstrated that the cooperative effect that combines the microlens function of the PS microspheres and the enhanced Rayleigh scattering of the ZnO nanoparticle porous layers can be used to greatly reduce the total internal reflection at the medium-air interface. The PS/ZnO hierarchical structures were fabricated on the surface of GaN-based light-emitting diode (LED) chips to enhance the light extraction efficiency. A 77.7% improvement on the light-output power was realized, which was much greater than that obtained with the PS microstructures alone. PMID- 26280449 TI - When Eating Right, Is Measured Wrong! A Validation and Critical Examination of the ORTO-15 Questionnaire in German. AB - The characteristic trait of individuals developing a pathological obsession and preoccupation with healthy foods and a restrictive and avoidant eating behavior is described as orthorexia nervosa (ON). For ON, neither universal diagnosis criteria nor valid tools for large-scale epidemiologic assessment are available in the literature. The aim of the current study is to analyze the psychometric properties of a translated German version of the ORTO-15 questionnaire. The German version of the ORTO-15, a eating behavior and dieting habits questionnaire were completed by 1029 German-speaking participants (74.6% female) aged between 19 and 70 years (M = 31.21 +/- 10.43 years). Our results showed that after confirmatory factor analysis, the best fitting model of the original version is a single-factor structure (9-item shortened version: ORTO-9-GE). The final model showed only moderate internal consistency (Cronbach's alpha = .67), even after omitting 40% of the original question. A total of 69.1% participants showed orthorectic tendencies. Orthorectic tendencies are associated with special eating behavior features (dieting frequency, vegetarian and vegan diet). Education level did not influence ON tendency and nutritional students did not show higher ON tendency compared to students from other disciplines. This study is the first attempt to translate and to evaluate the psychometric properties of a German version of the ORTO-15 questionnaire. The ORTO-9-GE questionnaire, however, is only a mediocre tool for assessing orthorectic tendencies in individuals and shows moderate reliability and internal consistency. Our research suggests, that future studies are needed to provide more reliable and valid assessment tools to investigate orthorexia nervosa. PMID- 26280450 TI - JMS: An Open Source Workflow Management System and Web-Based Cluster Front-End for High Performance Computing. AB - Complex computational pipelines are becoming a staple of modern scientific research. Often these pipelines are resource intensive and require days of computing time. In such cases, it makes sense to run them over high performance computing (HPC) clusters where they can take advantage of the aggregated resources of many powerful computers. In addition to this, researchers often want to integrate their workflows into their own web servers. In these cases, software is needed to manage the submission of jobs from the web interface to the cluster and then return the results once the job has finished executing. We have developed the Job Management System (JMS), a workflow management system and web interface for high performance computing (HPC). JMS provides users with a user friendly web interface for creating complex workflows with multiple stages. It integrates this workflow functionality with the resource manager, a tool that is used to control and manage batch jobs on HPC clusters. As such, JMS combines workflow management functionality with cluster administration functionality. In addition, JMS provides developer tools including a code editor and the ability to version tools and scripts. JMS can be used by researchers from any field to build and run complex computational pipelines and provides functionality to include these pipelines in external interfaces. JMS is currently being used to house a number of bioinformatics pipelines at the Research Unit in Bioinformatics (RUBi) at Rhodes University. JMS is an open-source project and is freely available at https://github.com/RUBi-ZA/JMS. PMID- 26280451 TI - Diversity and antimicrobial activity of endophytic fungi isolated from Cephalotaxus hainanensis Li, a well-known medicinal plant in China. AB - About 1051 endophytic fungi were isolated from leaves, branches, barks and stems of Cephalotaxus hainanensis Li from four sites in Hainan, China. The fungi were identified as 21 genera by morphology and ITS sequences. One dominant species was Phomopsis quercella in Hainan Tropical Botanical Garden and Bawangling Nature Reserve, with relative frequency of 42.06 and 34.88% respectively. Another dominant species was Colletotrichum boninense in Wuzhishan and Jianfengling Nature Reserves, with relative frequency of 36.84 and 46.97% respectively. Among the selected 21 endophytic fungi, 17 strains (80.95%) had activity against at least one pathogenic bacteria, and 14 strains (66.67%) exhibited activity against at least one fungal pathogens. Neonectria macroconidialis showed strong inhibition against Staphylococcus aureus (inhibition zone being 20 mm), Bacillus subtilis (14 mm) and Streptococcus agalactiae (28 mm). Xylaria sp. showed strong inhibition against Escherichia coli (20 mm), Rhizoctonia solani (20 mm) and Sclerotinia sclerotiorum (17 mm). Verticillium bulbillosum showed great activity against Strep. agalactiae (32 mm) and Fusarium oxysporum (22 mm). These endophytic fungi showed potentials in medicine development. SIGNIFICANCE AND IMPACT OF THE STUDY: Endophytic fungi from medicinal plants are an important source of novel and viable drugs. Cephalotaxus hainanensis Li is well known for leukaemia treatment and its endophytic fungi were isolated to investigate the diversity and antimicrobial activity. It was found that Ce. hainanensis Li had rich endophytic fungi, and some fungi showed strong antimicrobial activity against certain pathogens. These fungi can be used in medicine development. PMID- 26280452 TI - Task-specific kinetic finger tremor affects the performance of carrom players. AB - We aimed to determine the effect of task-specific kinetic finger tremor, as indexed by surface electromyography (EMG), on the accuracy of a carrom stroke. Surface EMG of extensor digitorum communis muscle of the playing arm was recorded during rest, isometric contraction and stroke execution in 17 male carrom players with clinically observed finger tremor and 18 skill- and age-matched controls. Log-transformed power spectral densities (LogPSDs) of surface EMG activity (signifying tremor severity) at a 1-s pre-execution period correlated with angular error of the stroke. LogPSDs in 4-10 Hz range were higher in players with tremor than controls during pre-execution (P < 0.001), but not during the resting state (P = 0.067). Pre-execution tremor amplitude correlated with angular deviation (r = 0.45, P = 0.007). For the first time, we document a task-specific kinetic finger tremor in carrom players. This finger tremor during the immediate pre-execution phase appears to be a significant determinant of stroke accuracy. PMID- 26280453 TI - Structural Determinants for the Binding of Morphinan Agonists to the MU-Opioid Receptor. AB - Atomistic descriptions of the MU-opioid receptor (MUOR) noncovalently binding with two of its prototypical morphinan agonists, morphine (MOP) and hydromorphone (HMP), are investigated using molecular dynamics (MD) simulations. Subtle differences between the binding modes and hydration properties of MOP and HMP emerge from the calculations. Alchemical free energy perturbation calculations show qualitative agreement with in vitro experiments performed in this work: indeed, the binding free energy difference between MOP and HMP computed by forward and backward alchemical transformation is 1.2+/-1.1 and 0.8+/-0.8 kcal/mol, respectively, to be compared with 0.4+/-0.3 kcal/mol from experiment. Comparison with an MD simulation of MUOR covalently bound with the antagonist beta-funaltrexamine hints to agonist-induced conformational changes associated with an early event of the receptor's activation: a shift of the transmembrane helix 6 relative to the transmembrane helix 3 and a consequent loss of the key R165-T279 interhelical hydrogen bond. This finding is consistent with a previous proposal suggesting that the R165-T279 hydrogen bond between these two helices indicates an inactive receptor conformation. PMID- 26280454 TI - Do rural and urban women experience differing rates of maternal rehospitalizations? AB - INTRODUCTION: Conditions such as postpartum complications and mental disorders of new mothers contribute to a relatively large number of maternal rehospitalizations and even some deaths. Few studies have examined rural-urban differences in hospital readmissions, and none of them have addressed maternal readmissions. This research directly compares readmissions for patients who delivered in rural versus urban hospitals. METHODS: The data for this cross sectional study were drawn from the 2011 California Healthcare Cost and Utilization Project. Readmission rates were reported to demonstrate rural-urban differences. Generalized estimating equation models were also used to estimate the likelihood of a new mother being readmitted over time. RESULTS: The 323 051 women who delivered with minor assistance and 158 851 women who delivered by cesarean section (C-section) were included in this study. Of those, seven maternal mortalities occurred after vaginal deliveries and 14 occurred after C section procedures. Fewer than 1% (0.98% or 3171) women with normal deliveries were rehospitalized. The corresponding number for women delivering via C-section was 1.41% (2243). For both types of deliveries, women giving birth in a rural hospital were more likely to be readmitted. CONCLUSIONS: This is the first study examining rural-urban differences in maternal readmissions. The results indicate the importance of monitoring and potentially improving the quality of maternal care, especially when the delivery involves a C-section. More studies investigating rural health disparities in women's health are clearly necessary. PMID- 26280456 TI - Localization of the bioluminescence system in the pileus of Mycena chlorophos. AB - Mycena chlorophos, which is primarily distributed in Southeast Asia, is a luminous fungus that emits a bright green light from its pileus for about 2 days at approximately 20 degrees C and high relative humidity. The distribution of bioluminescent tissues in the whole pileus and its sections was heterogeneous. The light intensity in the cap and the upper region of the gill was greater than that in the lower region of the gill. At the microscopic level, the light was predominantly emitted from the membranes of hymenium and basidia cells on the gill. The emission was both cell and region specific. The luminescence system was localized in the cell membrane, and a part of the system was on the cell membrane surface. PMID- 26280455 TI - Combined Salvianolic Acid B and Ginsenoside Rg1 Exerts Cardioprotection against Ischemia/Reperfusion Injury in Rats. AB - Lack of pharmacological strategies in clinics restricts the patient prognosis with myocardial ischemia/reperfusion (I/R) injury. The aim of this study was to evaluate the cardioprotection of combined salvianolic acid B (SalB) and ginsenoside Rg1 (Rg1) against myocardial I/R injury and further investigate the underlying mechanism. I/R injury was induced by coronary artery ligation for Wistar male rats and hypoxia/reoxygenation injury was induced on H9c2 cells. Firstly, the best ratio between SalB and Rg1was set as 2:5 based on their effects on heart function detected by hemodynamic measurement. Then SalB-Rg1 (2:5) was found to maintain mitochondrial membrane potential and resist apoptosis and necrosis in H9c2 cell with hypoxia/reoxygenation injury. Companying with same dose of SalB or Rg1 only, SalB-Rg1 showed more significant effects on down regulation of myocardial infarct size, maintenance of myocardium structure, improvement on cardiac function, decrease of cytokine secretion including TNF alpha, IL-1beta, RANTES and sVCAM-1. Finally, the SalB-Rg1 improved the viability of cardiac myocytes other than cardiac fibroblasts in rats with I/R injury using flow cytometry. Our results revealed that SalB-Rg1 was a promising strategy to prevent myocardial I/R injury. PMID- 26280458 TI - High-quality digital photomicrography utilizing a smartphone without adapter. PMID- 26280459 TI - Gene Expression of Monocarboxylate Transporters and Oocyte-secreted Factors in Bovine Cumulus-oocyte Complexes Selected by Brilliant Cresyl Blue. AB - Oocyte selection based on the brilliant cresyl blue (BCB) staining test has been successfully used to differentiate between competent and incompetent bovine oocytes. Here, the expression of genes involved in transport of monocarboxylates (Mct1-4) and oogenesis specific genes (Bmp15, Gdf9 and Has2) in BCB+ and BCB- selected immature and mature bovine cumulus-oocyte complexes (COC) was evaluated. In order to find specific molecular markers to characterize successful oocyte maturation, our study was also aimed at identifying the expression of Mcts and oogenesis specific genes in denuded oocytes and cumulus cells. Immature COCs morphological appropriate were (i) stained with 26 mm BCB for 90 min before IVM, (ii) exposed to same incubation conditions as stained COCs, but without BCB (holding group) or (iii) transferred into a maturation medium immediately after morphological selection (control group). mRNA expression was investigated by RT PCR in COCs before and after IVM. No relationship was observed in the relative expression of Has2, Gdf9, Bmp15 or Mct1, 2 and 4 transcripts between BCB+ and BCB COCs. Transcripts analysis showed that Gdf9 and Bmp15 in BCB+, BCB- and holding groups were up-regulated (p < 0.05) before IVM, while Has2 was up-regulated (p < 0.01) after IVM in the control group. Other genes remained stable during maturation (Mct1, 2 and 4). Our results showed, for the first time, Mct1, 2 and 4 expression in bovine COCs. Mct1 and Mct4 transcripts were present in denuded oocytes and cumulus cell, while Mct2 was detected only in cumulus cells. These differences between the three isoforms in localization suggest unique roles for each in monocarboxylate transport during maturation. PMID- 26280460 TI - Long-term visual outcome after chemotherapy for optic pathway glioma in children: Site and age are strongly predictive. AB - BACKGROUND: Optic pathway gliomas (OPGs) are commonly noted in pediatric oncology services. Radiotherapy is effective at controlling tumors, but has many undesirable late effects, especially in patients with neurofibromatosis. Chemotherapy is commonly used to preserve vision and delay or eliminate the need for radiotherapy. Despite visual threat being a common reason to initiate chemotherapy in patients with OPG, reports of visual outcome after chemotherapy are not common and reports of long-term visual outcome are even scarcer. METHODS: In a single institution, all patients with OPG who had received chemotherapy or radiotherapy between 1996 and 2013 were identified from hospital databases. Visual, treatment, and radiological data were recorded. Categorized visual acuity was the primary outcome measure. RESULTS: Of 43 patients identified, visual data were available for 42 patients. Approximately 14% of patients experienced an improvement in visual acuity during therapy, 9% of patients experienced a deterioration, and the remainder were stable. At a mean follow-up of 78 months, 26% of patients were legally blind. Children aged <2 years and patients with a chiasmatic/hypothalamic tumor site were overrepresented in this category. An intraconal location was predictive of poor visual outcome for that eye but was unilateral with normal vision in the contralateral eye. CONCLUSIONS: Risk factors for long-term visual deterioration are young age, chiasmatic/hypothalamic tumor site, and intraconal tumor site for the involved eye. The most common visual outcome for children with OPG after treatment with chemotherapy is stability. This stability is maintained over the long term for >90% of children without these risk factors. PMID- 26280461 TI - Transcriptome analysis of Streptococcus gordonii Challis DL1 indicates a role for the biofilm-associated fruRBA operon in response to Candida albicans. AB - Multiple levels of interkingdom signaling have been implicated in maintaining the ecological balance between Candida albicans and commensal streptococci to assure a state of oral health. To better understand the molecular mechanisms involved in the initial streptococcal response to the presence of C. albicans that can initiate oral surface colonization and biofilm formation, hypha-forming cells were incubated with Streptococcus gordonii cells for 30 min to assess the streptococcal transcriptome response. A genome-wide microarray analysis and quantitative polymerase chain reaction validation of S. gordonii transcripts identified a number of genes, the majority of which were involved in metabolic functions that were differentially expressed in the presence of hyphae. The fruR, fruB, and fruA genes encoding the transcriptional regulator, fructose-1-phosphate kinase, and fructose-specific permease, respectively, of the phosphoenolpyruvate dependent fructose phosphotransferase system, were consistently upregulated. An S. gordonii mutant in which these genes were deleted by allelic replacement formed an architecturally distinct, less robust biofilm with C. albicans than did parental strain cells. Complementing the mutant with plasmid borne fruR, fruB, and fruA genes caused phenotype reversion, indicating that the genes in this operon played a role in dual-species biofilm formation. This genome-wide analysis of the S. gordonii transcriptional response to C. albicans has identified several genes that have potential roles in interkingdom signaling and responses. PMID- 26280462 TI - "Best Case/Worst Case": Qualitative Evaluation of a Novel Communication Tool for Difficult in-the-Moment Surgical Decisions. AB - OBJECTIVES: To evaluate a communication tool called "Best Case/Worst Case" (BC/WC) based on an established conceptual model of shared decision-making. DESIGN: Focus group study. SETTING: Older adults (four focus groups) and surgeons (two focus groups) using modified questions from the Decision Aid Acceptability Scale and the Decisional Conflict Scale to evaluate and revise the communication tool. PARTICIPANTS: Individuals aged 60 and older recruited from senior centers (n = 37) and surgeons from academic and private practices in Wisconsin (n = 17). MEASUREMENTS: Qualitative content analysis was used to explore themes and concepts that focus group respondents identified. RESULTS: Seniors and surgeons praised the tool for the unambiguous illustration of multiple treatment options and the clarity gained from presentation of an array of treatment outcomes. Participants noted that the tool provides an opportunity for in-the-moment, preference-based deliberation about options and a platform for further discussion with other clinicians and loved ones. Older adults worried that the format of the tool was not universally accessible for people with different educational backgrounds, and surgeons had concerns that the tool was vulnerable to physicians' subjective biases. CONCLUSION: The BC/WC tool is a novel decision support intervention that may help facilitate difficult decision-making for older adults and their physicians when considering invasive, acute medical treatments such as surgery. PMID- 26280464 TI - SCC-DFTB parameters for simulating hybrid gold-thiolates compounds. AB - We present a parametrization of a self-consistent charge density functional-based tight-binding scheme (SCC-DFTB) to describe gold-organic hybrid systems by adding new Au-X (X = Au, H, C, S, N, O) parameters to a previous set designed for organic molecules. With the aim of describing gold-thiolates systems within the DFTB framework, the resulting parameters are successively compared with density functional theory (DFT) data for the description of Au bulk, Aun gold clusters (n = 2, 4, 8, 20), and Aun SCH3 (n = 3 and 25) molecular-sized models. The geometrical, energetic, and electronic parameters obtained at the SCC-DFTB level for the small Au3 SCH3 gold-thiolate compound compare very well with DFT results, and prove that the different binding situations of the sulfur atom on gold are correctly described with the current parameters. For a larger gold-thiolate model, Au25 SCH3 , the electronic density of states and the potential energy surfaces resulting from the chemisorption of the molecule on the gold aggregate obtained with the new SCC-DFTB parameters are also in good agreement with DFT results. PMID- 26280463 TI - Validation of a contemporary adherence measure for children with Type 1 diabetes: the Diabetes Management Questionnaire. AB - AIMS: To evaluate the psychometric properties of the Diabetes Management Questionnaire, a brief, self-report measure of adherence to contemporary diabetes management for young people with Type 1 diabetes and their caregivers. METHODS: A total of 273 parent-child dyads completed parallel versions of the Diabetes Management Questionnaire. Eligible children (aged 8-18 years) had Type 1 diabetes for >=1 year. A multidisciplinary team designed the Diabetes Management Questionnaire as a brief, self-administered measure of adherence to Type 1 diabetes management over the preceding month; higher scores reflect greater adherence. Psychometrics were evaluated for the entire sample and according to age of the child. RESULTS: The children (49% female) had a mean +/- sd (range) age 13.3 +/- 2.9 (8-18) years and their mean +/- sd HbA1c was 71 +/- 15 mmol/mol (8.6 +/- 1.4%). Internal consistency was good for parents (alpha = 0.83) and children (alpha = 0.79). Test-retest reliability was excellent for parents (intraclass correlation coefficient =0.83) and good for children (intraclass correlation coefficient = 0.65). Parent and child scores had moderate agreement (intraclass correlation coefficient = 0.54). Diabetes Management Questionnaire scores were inversely associated with HbA1c (parents: r = -0.41, P < 0.0001; children: r = -0.27, P < 0.0001). Psychometrics were stronger in the children aged >=13 years compared with those aged < 13 years, but were acceptable in both age groups. Mean +/- sd Diabetes Management Questionnaire scores were higher among children who were receiving insulin pump therapy (n = 181) than in children receiving multiple daily injections (n = 92) according to parent (75.9 +/- 11.8 vs. 70.5 +/- 15.5; P = 0.004) and child report (72.2 +/- 12.1 vs. 67.6 +/- 13.9; P = 0.006). CONCLUSIONS: The Diabetes Management Questionnaire is a brief, valid self-report measure of adherence to contemporary diabetes self-management for people aged 8-18 years who are receiving either multiple daily injections or insulin pump therapy. PMID- 26280465 TI - Incomplete erythropoietic protoporphyria caused by a splice site modulator homozygous IVS3-48C polymorphism in the ferrochelatase gene. AB - Erythropoietic protoporphyria (EPP) is an inherited cutaneous porphyria caused by both the partial deficiency of ferrochelatase (FECH) and the existence of cytosine at IVS3-48 in trans to a mutated FECH allele. However, physicians occasionally encounter patients with EPP with a mild phenotype associated with a slight increase in the erythrocyte-free protoporphyrin concentration and no FECH gene mutations. In this study, genetic analyses were performed on three patients with a mild phenotype of EPP, with photosensitivity, slightly increased erythrocyte-free protoporphyrin concentrations and only a few fluorocytes in the peripheral blood. After obtaining the patients' and their parents' informed consent, a direct sequence analysis of the FECH gene and a restriction fragment length polymorphism analysis were performed on samples from the patients. The FECH gene mutation was not detected in the direct sequence analyses in any of the patients. However, all three patients had the homozygous IVS3-48C polymorphism. These findings suggest that homozygous IVS3-48C polymorphism of the FECH gene is associated with a slight elevation of the protoporphyrin level in erythrocytes, resulting in a mild EPP phenotype. PMID- 26280467 TI - How do Student Clients of a University-based Food Bank Cope with Food Insecurity? AB - PURPOSE: To describe the food security status, food insecurity coping strategies, characteristics, and experiences of student clients of the Campus Food Bank (CFB) at the University of Alberta in Edmonton, Alberta, Canada. METHODS: A convenience sample of 58 students completed a survey from April 2013 to April 2014. Food security status was determined using the "Adult Food Security Survey Module". RESULTS: Ninety percent of CFB student clients who participated in this study were food insecure, which included both moderately and severely food insecure groups. The most prevalent coping strategies for food insecurity included applying for a loan or bursary (86.2%), seeking employment or working more hours (84.5%), and purchasing food using a credit card (77.6%). Participants were a diverse mix of students, including graduate students (50.0%), international students (46.6%), and caregivers of children (24.1%). The most common primary sources of income were government student loans (29.3%) and research assistantships (20.7%). Most participants (82.8%) liked the food they received from the food bank. CONCLUSIONS: Food insecurity is highly prevalent among student clients of this university-based food bank. Students used a variety of coping strategies to increase their disposable income, highlighting the need for additional strategies to alleviate food insecurity among vulnerable students. PMID- 26280466 TI - The Current and Potential Clinical Relevance of Heart Failure Biomarkers. AB - Heart failure is a growing epidemic, and our understanding of the intricacies of its pathophysiology continues to evolve. Over the last decade, biomarkers of heart failure have been extensively investigated, particularly for diagnosis and risk stratification. While the natriuretic peptides remain the gold standard heart failure biomarker, they are plagued by their non-specific nature; furthermore, the strategy of natriuretic peptide-guided care remains elusive. Multiple candidate markers indicative of other physiologic aspects of heart failure have been identified and studied, including soluble ST2, galectin-3, and high-sensitivity cardiac troponins. Each of these biomarkers has the potential to provide unique therapeutically relevant information. Ultimately, a multi-marker approach may be applied to improve care of patients with heart failure. Definitive clinical trials and the use of advanced statistical analytic techniques are needed to truly determine the optimal strategy of biomarker assisted diagnosis, prognostication, and management of patients who suffer from this devastating condition. PMID- 26280468 TI - The role of vaccinia termination factor and cis-acting elements in vaccinia virus early gene transcription termination. AB - Vaccinia virus early gene transcription termination requires the virion form of the viral RNA polymerase (vRNAP), Nucleoside Triphosphate Phosphohydrolase I (NPHI), ATP, the vaccinia termination factor (VTF), and a U5NU termination signal in the nascent transcript. VTF, also the viral mRNA capping enzyme, binds U5NU, and NPHI hydrolyzes ATP to release the transcript. NPHI can release transcripts independent of VTF and U5NU if vRNAP is not actively elongating. However, VTF and U5NU are required for transcript release from an elongating vRNAP, suggesting that the function of VTF and U5NU may be to stall the polymerase. Here we demonstrate that VTF inhibits transcription elongation by enhancing vRNAP pausing. Hence VTF provides the connection between the termination signal in the RNA transcript and viral RNA polymerase to initiate transcription termination. We also provide evidence that a second cis-acting element downstream of U5NU influences the location and efficiency of early gene transcription termination. PMID- 26280470 TI - Nutrient database improvement project: Separable components and proximate composition of raw and cooked retail cuts from the beef loin and round. AB - Beef nutrition research has become increasingly important domestically and internationally for the beef industry and its consumers. The objective of this study was to analyze the nutrient composition of ten beef loin and round cuts to update the nutrient data in the USDA National Nutrient Database for Standard Reference. Seventy-two carcasses representing a national composite of Yield Grade, Quality Grade, sex classification, and genetic type were identified from six regions across the U.S. Beef short loins, strip loins, tenderloins, inside rounds, and eye of rounds (NAMP # 173, 175, 190A, 169A, and 171C) were collected from the selected carcasses and shipped to three university meat laboratories for storage, retail fabrication, and raw/cooked analysis of nutrients. Sample homogenates from each animal were analyzed for proximate composition. These data provide updated information regarding the nutrient status of beef, in addition, to determining the influence of Quality Grade, Yield Grade, and sex classification on nutrient composition. PMID- 26280471 TI - Adsorption and degradation processes of tributyltin and trimethyltin in landfill leachates treated with iron nanoparticles. AB - Biotic and abiotic degradation of toxic organotin compounds (OTCs) in landfill leachates is usually not complete. In this work adsorption and degradation processes of tributyltin (TBT) and trimethyltin (TMeT) in leachate sample treated with different iron nanoparticles (FeNPs): Fe(0) (nZVI), FeO and Fe3O4 were investigated to find conditions for their efficient removal. One sample aliquot was kept untreated (pH 8), while to the others (pH 8) FeNPs dispersed with tetramethyl ammonium hydroxide (TMAH) or by mixing were added and samples shaken under aerated conditions for 7 days. The same experiments were done in leachates in which the pH was adjusted to 3 with citric acid. Size distribution of TBT and TMeT between particles >5 um, 0.45-5 um, 2.5-0.45 um, and <2.5 nm was determined by sequential filtration and their concentrations in a given fraction by gas chromatography coupled to inductively coupled plasma mass spectrometry (GC-ICP MS). Results revealed that most of the TBT or TMeT was present in fractions with particles >2.5 or <2.5 nm, respectively. At pH 8 adsorption of TBT to FeNPs prevailed, while at pH 3, the Fenton reaction provoked degradation of TBT by hydroxyl radicals. TBT was the most effectively removed (96%) when sequential treatment of leachate with nZVI (dispersed by mixing) was applied first at pH 8, followed by nZVI treatment of the aqueous phase, previously acidified to pH 3 with citric acid. Such treatment less effectively removed TMeT (about 40%). It was proven that TMAH provoked methylation of tin, so mixing was recommended for dispersion of nZVI. PMID- 26280469 TI - Variation in interferon sensitivity and induction between Usutu and West Nile (lineages 1 and 2) viruses. AB - Given the pivotal role of monocyte-derived dendritic cells (DCs) in determining the magnitude of the antiviral innate immune response, we sought to determine whether Usutu virus (USUV) and West Nile virus (WNV) lineages (L)1 and L2 can infect DCs and affect the rate of type I interferon (IFN) activation. The sensitivity of these viruses to types I and III IFNs was also compared. We found that USUV can infect DCs, induce higher antiviral activities, IFN alpha subtypes and the IFN stimulated gene (ISG)15 pathway, and is more sensitive to types I and III IFNs than WNVs. In contrast, we confirmed that IFN alpha/beta subtypes were more effective against WNV L2 than WNV L1. However, the replication kinetics, induction of IFN alpha subtypes and ISGs in DCs and the sensitivity to IFN lambda 1-3 did not differ between WNV L1 and L2. PMID- 26280472 TI - Dynamic Distraction External Fixation for Contracture of the Metacarpophalangeal Joint. AB - Metacarpophalangeal (MP) joint contractures are common after traumatic injury, and can be difficult to manage. After surgical capsulectomy, it remains challenging to maintain motion that was obtained at the time of surgery. Our group uses a novel, prefabricated digital external fixator to provide both distraction, and motion therapy across the MP joint after surgical treatment of MP contracture. The purpose of this technique is to demonstrate the effectiveness of an adjunctive dynamic distraction external fixator for the maintenance of joint motion after surgical treatment of MP contractures of the border digits. PMID- 26280473 TI - Neosaxitoxin in Rat Sciatic Block: Improved Therapeutic Index Using Combinations with Bupivacaine, with and without Epinephrine. AB - BACKGROUND: Neosaxitoxin (NeoSTX) is a site-1 sodium channel blocker undergoing clinical trials as a prolonged-duration local anesthetic. Rat sciatic block and intravenous infusion models were used to assess efficacy and local and systemic toxicities for NeoSTX in saline (NeoSTX-Saline), bupivacaine (Bup), and their combination (NeoSTX-Bup). Exploratory studies evaluated the effects of addition of epinephrine to NeoSTX-Bup (NeoSTX-Bup-Epi). METHODS: Rats received percutaneous sciatic blocks with escalating doses of NeoSTX-Saline or NeoSTX-Bup. Sensory-nocifensive block was assessed using modified hotplate and Von Frey filaments. Motor-proprioceptive function was assessed by extensor postural thrust. Nerves were examined histologically after 7 days and scored on the Estebe Myers scale. Median lethal dose was estimated for NeoSTX-Saline and in combinations. Accidental intravenous overdose was simulated in isoflurane anesthetized, spontaneously breathing rats receiving NeoSTX-Saline (n = 6), Bup (n = 7), or NeoSTX-Bup (n = 13), with respiratory, hemodynamic, and electrocardiographic endpoints. Additional groups received blocks with NeoSTX-Bup Epi (n = 80). Investigators were blinded for behavioral and histologic studies. RESULTS: NeoSTX-Bup produced more prolonged sensory and motor block compared with NeoSTX-Saline or Bup. NeoSTX-Bup-Epi further prolonged median time to near complete recovery for 3 MUg/kg NeoSTX-Bup (hotplate: 48 vs. 6 h, P < 0.001). With sciatic injections, addition of Bup did not worsen the systemic toxicity (median lethal dose) compared with NeoSTX-Saline. Intravenous NeoSTX-Saline infusion had significantly longer times to apnea, first arrhythmia, and asystole compared with Bup (P < 0.001 for each). Histologic injury scores overall were low for all groups, with median scores of 0 (interquartile range, 0 to 0) on a 5-point scale. CONCLUSION: NeoSTX-Bup and NeoSTX-Bup-Epi hold promise for prolonged-duration local anesthesia. PMID- 26280474 TI - Computed Tomography Screening for Lung Cancer in the National Lung Screening Trial: A Cost-effectiveness Analysis: Erratum. PMID- 26280485 TI - Early Periimplant Tissue Healing on 1-Piece Implants With a Concave Transmucosal Design: A Histomorphometric Study in Dogs. AB - INTRODUCTION: The purpose of our study was to investigate the early healing phase of marginal bone and soft tissues around unloaded 1-piece implants with a concave transmucosal design, in a dog model. METHODS: Twenty-four 1-piece implants with a concave transmucosal neck were inserted 1 mm subcrestally in the mandibular ridge of 8 beagle dogs. Four animals were sacrificed after 3 and 12 weeks of healing. Histomorphometric analysis was performed to measure the height of the periimplant tissues. RESULTS AND DISCUSSION: The overall height of the periimplant mucosa was, respectively, 2.67 and 2.52 mm, after 3 and 12 weeks. In the connective tissue, a soft tissue O-ring seal was observed in the healing area provided by the transmucosal concavity, after 12 weeks. The location of the first bone-to implant contact facing the implant shoulder was 0.00 and +0.18 mm, respectively, after 3 and 12 weeks of healing. Some bone apposition occurred on the implant shoulder during the healing. CONCLUSION: Within the limits of the present study, a concave transmucosal design in 1-piece implants was associated with a short vertical value of biological width and promoted a mechanical interlocking of the implant body at the connective tissue and marginal bone levels. PMID- 26280486 TI - Emergency resuscitative thoracotomy performed in European civilian trauma patients with blunt or penetrating injuries: a systematic review. AB - PURPOSE: Emergency resuscitative thoracotomy (ERT) is a lifesaving procedure in selected patients. Indications are still being debated, but outcome in blunt trauma is believed to be poor. Recent reports from European populations, where blunt trauma predominates, have suggested favorable outcome also in blunt trauma. Our aim was to identify all European studies reported over the last decade and compare reported outcomes to existing knowledge. METHODS: We performed a systematic literature search according to PRISMA guidelines (January 1st, 2004 to December 31st, 2014). The "grey literature" was included by searching Google Scholar. Qualitative comparison of studies and outcomes was done. RESULTS: A total of 8 articles from Europe were included originating from Croatia, Norway (n = 2), Denmark, Iceland, the Netherlands, Scotland, and Switzerland. Of 376 resuscitative thoracotomies, 193 (51.3 %) were for blunt trauma. Male:female distribution was 3.5:1. The collectively reported overall survival was 42.8 % (n = 161), with 25.4 % (49 of 193) blunt trauma and 61.2 % (112 of 183) penetrating injuries. When strictly including those ERTs designated as done in the emergency department for blunt mechanism (n = 139) only, a total of 18 patients survived (12.9 %). Survival after EDTs for penetrating trauma was 41.6 % (37 of 89). Neurological outcome (reported in 5 of 8 studies) reported favorable neurological long-term outcome in the majority of survivors, even after blunt trauma. None referred to Glasgow Outcome Score. Heterogeneity in the studies prevented outcome analyses by formal quantitative meta-analysis. CONCLUSION: The reported outcome after ERT in European civilian trauma populations is favorable, with one in every four ERTs in the ED surviving. Notably, outcome is at variance with previously reported collective data, in particular for blunt trauma. Multicenter, prospective, observational data are needed to validate the modern role of ERT in blunt trauma. PMID- 26280488 TI - How differentiated do children experience affect? An investigation of the within- and between-person structure of children's affect. AB - Research on the structure of children's affect is limited. It is possible that children's perception of their own affect might be less differentiated than that of adults. Support for the 2-factor model of positive and negative affect and the pleasure-arousal model suggests that children in middle childhood can distinguish positive and negative affect as well as valence and arousal. Whether children are able to differentiate further aspects of affect, as proposed by the 3-dimensional model of affect (good-bad mood, alertness-tiredness, calmness-tension), is an unresolved issue. The aim of our study was the comparison of these 3 affect models to establish how differentiated children experience their affect and which model best describes affect in children. We examined affect structures on the between- and within-person level, acknowledging that affect varies across time and that no valid interpretation of either level is feasible if both are confounded. For this purpose, 214 children (age 8-11 years) answered affect items once a day for 5 consecutive days on smartphones. We tested all affect models by means of 2-level confirmatory factor analysis. Although all affect models had an acceptable fit, the 3-dimensional model best described affect in children on both the within- and between-person level. Thus, children in middle childhood can already describe affect in a differentiated way. Also, affect structures were similar on the within- and between-person level. We conclude that in order to acquire a thorough picture of children's affect, measures for children should include items of all 3 affect dimensions. (PsycINFO Database Record PMID- 26280487 TI - Development and validation of the Acculturative Stress Scale for Chinese College Students in the United States (ASSCS). AB - Chinese students are the biggest ethnic group of international students in the United States. This study aims to develop a reliable and valid scale to accurately measure their acculturative stress. A 72-item pool was sent online to Chinese students and a five-factor scale of 32 items was generated by exploratory factor analysis. The five factors included language insufficiency, social isolation, perceived discrimination, academic pressure, and guilt toward family. The Acculturative Stress Scale for Chinese Students demonstrated high reliability and initial validity by predicting depression and life satisfaction. It was the first Chinese scale of acculturative stress developed and validated among a Chinese student sample in the United States. In the future, the scale can be used as a diagnostic tool by mental health professionals and a self-assessment tool by Chinese students. PMID- 26280489 TI - Psychometric properties of the Spanish version of the UPPS-P Impulsive Behavior Scale: A Rasch rating scale analysis and confirmatory factor analysis. AB - The present study was aimed at determining the psychometric properties of the Spanish version of the UPPS-P Impulsive Behavior Scale in a sample of college students. Participants were 318 college students (36.2% men; mean age = 20.9 years, SD = 6.4 years). The psychometric properties of this Spanish version were analyzed using the Rasch model, and the factor structure was examined using confirmatory factor analysis. The verification of the global fit of the data showed adequate indexes for persons and items. The reliability estimates were high for both items and persons. Differential item functioning across gender was found for 23 items, which likely reflects known differences in impulsivity levels between men and women. The factor structure of the Spanish version of the UPPS-P replicates previous work with the original UPPS-P Scale. Overall, results suggest that test scores from the Spanish version of the UPPS-P show adequate psychometric properties to accurately assess the multidimensional model of impulsivity, which represents the most exhaustive measure of this construct. PMID- 26280490 TI - Development of N-(Functionalized benzoyl)-homocycloleucyl-glycinonitriles as Potent Cathepsin K Inhibitors. AB - Cathepsin K is a major drug target for osteoporosis and related-bone disorders. Using a combination of virtual combinatorial chemistry, QSAR modeling, and molecular docking studies, a series of cathepsin K inhibitors based on N (functionalized benzoyl)-homocycloleucyl-glycinonitrile scaffold was developed. In order to avoid previous problems of cathepsin K inhibitors associated with lysosomotropism of compounds with basic character that resulted in off-target effects, a weakly- to nonbasic moiety was incorporated into the P3 position. Compounds 5, 6, and 9 were highly selective for cathepsin K when compared with cathepsins L and S, with the Ki values in the 10-30 nM range. The kinetic studies revealed that the new compounds exhibited reversible tight binding to cathepsin K, while the X-ray structural studies showed covalent and noncovalent binding between the nitrile group and the catalytic cysteine (Cys25) site. PMID- 26280491 TI - Interest in spiritually integrated psychotherapy among acute psychiatric patients. AB - OBJECTIVE: Spiritually integrated psychotherapy (SIP) is increasingly common, though systematic assessment of interest in such treatments, and predictors of such interest, has not yet been conducted among acute psychiatric patients. METHODS: We conducted a survey with 253 acute psychiatric patients (95-99% response rate) at a private psychiatric hospital in Eastern Massachusetts to assess for interest in SIP, religious affiliation, and general spiritual or religious involvement alongside clinical and demographic factors. RESULTS: More than half (58.2%) of patients reported "fairly" or greater interest in SIP, and 17.4% reported "very much" interest. Demographic and clinical factors were not significant predictors except that current depression predicted greater interest. Religious affiliation and general spiritual or religious involvement were associated with more interest; however, many affiliated patients reported low or no interest (42%), and conversely many unaffiliated patients reported "fairly" or greater interest (37%). CONCLUSIONS: Many acute psychiatric patients, particularly individuals with major depression, report interest in integrating spirituality into their mental health care. Assessment of interest in SIP should be considered in the context of clinical care. PMID- 26280493 TI - In-Plane Anisotropy in Mono- and Few-Layer ReS2 Probed by Raman Spectroscopy and Scanning Transmission Electron Microscopy. AB - Rhenium disulfide (ReS2) is a semiconducting layered transition metal dichalcogenide that exhibits a stable distorted 1T phase. The reduced symmetry of this system leads to in-plane anisotropy in various material properties. Here, we demonstrate the strong anisotropy in the Raman scattering response for linearly polarized excitation. Polarized Raman scattering is shown to permit a determination of the crystallographic orientation of ReS2 through comparison with direct structural analysis by scanning transmission electron microscopy (STEM). Analysis of the frequency difference of appropriate Raman modes is also shown to provide a means of precisely determining layer thickness up to four layers. PMID- 26280494 TI - K2Ca4[(UO2)(Si2O7)2]: A Uranyl Silicate with a One-Dimensional Chain Structure. AB - A new uranyl silicate, K2Ca4[(UO2)(Si2O7)2], with a 1D chain structure has been synthesized from a solution of mixed alkali- and alkaline-earth-metal cations under hydrothermal conditions at 550 degrees C and 1400 bar and characterized by single-crystal X-ray diffraction and photoluminescence spectroscopy. It crystallizes in the triclinic space group P1 (No. 2) with a = 6.6354(2) A, b = 6.6791(2) A, c = 9.6987(3) A, alpha = 98.324(2) degrees , beta = 93.624(2) degrees , gamma = 112.310(2) degrees , and Z = 1. Its crystal structure consists of a 1D chain of uranyl disilicate formed of corner-sharing UO6 tetragonal bipyramids and Si2O7 double groups. The adjacent chains are separated by K(+) and Ca(2+) cations. It is the first example of uranyl silicate with a 1D chain structure. PMID- 26280492 TI - The mental health of sexual minority adults in and out of the closet: A population-based study. AB - OBJECTIVES: Previous studies have found that sexual orientation concealment affords escape from stigma and discrimination but also creates a psychological toll. While disclosure alleviates the mental burden of concealment, it invites the stress of navigating a new public identity. Population-based samples that include both "in" and "out" sexual minorities provide an ideal opportunity to resolve limitations and inconsistencies of previous nonprobability investigations into the mental health correlates of concealment and disclosure. METHOD: Sexual minority participants in the California Quality of Life Survey (n = 2,083) indicated whether and when they first disclosed their sexual orientation to others. Prevalence of 1-year major depressive disorder and generalized anxiety disorder was derived from the Composite International Diagnostic Interview-Short Form. RESULTS: Closeted men (n = 84) were less likely to be depressed than out men, n = 1,047; odds ratio (OR) = 0.41; 95% CI [0.17, 0.996]. Men who were recently out (n = 201) experienced higher odds of major depressive disorder, OR = 6.21; 95% CI [1.53, 24.47], and generalized anxiety disorder, OR = 5.51; 95% CI [1.51, 20.13], as compared to closeted men. Men who were distantly out (n = 846) also experienced higher odds of major depressive disorder than men who were closeted, OR = 2.91; 95% CI [1.10, 7.69]. Recently out women (n = 243) experienced lower odds of depression than closeted women, n = 63; OR = 0.21; 95% CI [0.05, 0.96]. CONCLUSION: Whether being in or out of the closet is associated with depression and anxiety largely depends on gender. Clinical and policy implications are discussed in terms of the unique stressors facing men and women both in and out of the closet. PMID- 26280495 TI - News From the International Council on Women's Health Issues. PMID- 26280496 TI - Exploring the functional locus of language switching: evidence from a PRP paradigm. AB - To identify the stages of language processing at which language switching takes place, we examined the effect of partially temporally overlapping language processing on language switch costs in a dual-task study, in which we varied the stimulus onset asynchrony (SOA), the language (German-English), and the language sequence (language repetition trials and language switch trials). Using language comprehension tasks, the data revealed an effect of SOA (i.e., the "PRP" effect) and language switch costs. However, we did not find any influence of SOA on language switch costs, which suggests that language switches occur at the stages of lexical selection or post-selection processing. Thus, the findings of the present study provide evidence for models that assume language control to occur during or after lexical selection. PMID- 26280497 TI - Retrieval monitoring is influenced by information value: the interplay between importance and confidence on false memory. AB - The perceived value of information can influence one's motivation to successfully remember that information. This study investigated how information value can affect memory search and evaluation processes (i.e., retrieval monitoring). In Experiment 1, participants studied unrelated words associated with low, medium, or high values. Subsequent memory tests required participants to selectively monitor retrieval for different values. False memory effects were smaller when searching memory for high-value than low-value words, suggesting that people more effectively monitored more important information. In Experiment 2, participants studied semantically-related words, and the need for retrieval monitoring was reduced at test by using inclusion instructions (i.e., endorsement of any word related to the studied words) compared with standard instructions. Inclusion instructions led to increases in false recognition for low-value, but not for high-value words, suggesting that under standard-instruction conditions retrieval monitoring was less likely to occur for important information. Experiment 3 showed that words retrieved with lower confidence were associated with more effective retrieval monitoring, suggesting that the quality of the retrieved memory influenced the degree and effectiveness of monitoring processes. Ironically, unless encouraged to do so, people were less likely to carefully monitor important information, even though people want to remember important memories most accurately. PMID- 26280498 TI - How do Young Adults View 12-Step Programs? A Qualitative Study. AB - Given the limited research on young adults' reactions to 12-step programs, the purpose of this study was to explore young adults' views of Alcoholics Anonymous and Narcotics Anonymous. Qualitative interviews with 26 young adults who had attended Alcoholics Anonymous or Narcotics Anonymous were conducted. Most participants viewed 12-step programs favorably, reporting that the programs provided hope and emotional support. Participants who rejected the programs often refused to accept the concepts of powerlessness and a higher power. Many participants who rejected Alcoholics Anonymous and Narcotics Anonymous were unaware of some of the key tenets of the programs, suggesting that 12-step facilitation would benefit this population. PMID- 26280500 TI - Following up on ISBER 2015: Call for Environmental Biobanking Papers. PMID- 26280499 TI - Nucleocytoplasmic shuttling of tRNAs and implication of the cytosolic Hsp70 system in tRNA import. AB - tRNAs, a class of non-coding RNAs essential for translation, are unique among cytosolic RNA species in that they shuttle between the nucleus and cytoplasm during their life. Although their export from the nucleus has been studied in detail, limited information on import machinery was available. Our group recently reported that Ssa2p, one of major cytosolic Hsp70s in Saccharomyces cerevisiae, acts as a crucial factor for tRNA import upon nutrient starvation. Ssa2p can bind tRNAs and a nucleoporin directly in an ATP-sensitive manner, suggesting that it acts as a nuclear import carrier for tRNAs, like importin-beta proteins. In vitro assays revealed that Ssa2p binds tRNA specifically but has preference for loosely folded tRNAs. In this Extra View, these features of Ssa2p as a new import factor is discussed with other recent findings related to nucleocytoplasmic transport of tRNAs reported from other groups. PMID- 26280501 TI - Cryopreservation of Human Mesenchymal Stem Cells for Clinical Applications: Current Methods and Challenges. AB - Mesenchymal stem cells (MSCs) hold many advantages over embryonic stem cells (ESCs) and other somatic cells in clinical applications. MSCs are multipotent cells with strong immunosuppressive properties. They can be harvested from various locations in the human body (e.g., bone marrow and adipose tissues). Cryopreservation represents an efficient method for the preservation and pooling of MSCs, to obtain the cell counts required for clinical applications, such as cell-based therapies and regenerative medicine. Upon cryopreservation, it is important to preserve MSCs functional properties including immunomodulatory properties and multilineage differentiation ability. Further, a biosafety evaluation of cryopreserved MSCs is essential prior to their clinical applications. However, the existing cryopreservation methods for MSCs are associated with notable limitations, leading to a need for new or improved methods to be established for a more efficient application of cryopreserved MSCs in stem cell-based therapies. We review the important parameters for cryopreservation of MSCs and the existing cryopreservation methods for MSCs. Further, we also discuss the challenges to be addressed in order to preserve MSCs effectively for clinical applications. PMID- 26280502 TI - Banking Brain Tumor Specimens Using a University Core Facility. AB - Within the past three decades, the significance of banking human cancer tissue for the advancement of cancer research has grown exponentially. The purpose of this article is to detail our experience in collecting brain tumor specimens in collaboration with the University of Miami/Sylvester Tissue Bank Core Facility (UM-TBCF), to ensure the availability of high-quality samples of central nervous system tumor tissue for research. Successful tissue collection begins with obtaining informed consent from patients following institutional IRB and federal HIPAA guidelines, and it needs a well-trained professional staff and continued maintenance of high ethical standards and record keeping. Since starting in 2011, we have successfully banked 225 brain tumor specimens for research. Thus far, the most common tumor histology identified among those specimens has been glioblastoma (22.1%), followed by meningioma (18.1%). The majority of patients were White, non-Hispanics accounting for 45.1% of the patient population; Hispanic/Latinos accounted for 23%, and Black/African Americans accounted for 14%, which represent the particular population of the State of Florida according to the 2010 census data. The most common tumors found in each subgroup were as follows: Black/African American, glioblastoma and meningioma; Hispanic, metastasis and glioblastoma; White, glioblastoma and meningioma. The UM-TBCF is a valuable repository, offering high-quality tumor samples from a unique patient population. PMID- 26280503 TI - Optimized Treatment of Heparinized Blood Fractions to Make Them Suitable for Analysis. AB - BACKGROUND: It has been known for decades that many cytokines, such as IL-2, IL 6, and IL-12, bind to heparin. Even though some enzyme-linked immunosorbent assays (ELISA) use antibody-recognizing epitopes not affected by this binding, ELISA manufacturers often warn that heparinized plasma or serum fractions containing more than 3 IU (international units)/mL of heparin should not be used in assays so as to prevent heparin interference in the reaction. In addition, enzyme-based nucleic acid amplifications from heparinized samples have been shown defective by several research groups. The aim of this study was to determine optimal degradation and/or removal of heparin from heparinized blood samples to best turn them into fractions for appropriate ELISA and RT-PCR analysis. METHODS AND RESULTS: A colorimetric reporter assay based on the metachromatic effect of the binding of heparin to toluidine blue was shown to be a low-cost effective method to discriminate assay compatible blood fractions with heparin levels below 3 IU/mL. Heparin removal from human blood fractions was best achieved by treatment with either Bacteroides Heparinase II or the less expensive Heparinase I at a final concentration of 0.1 U/MUL and incubations at 30 degrees C for a period between 30 min and 4 h, or by adsorption to Ecteola slurries at a concentration of 20 mg/mL for 20 min at room temperature (RT). The fact that both enzymatic and resin-based optimized treatments allowed for replication of the readings obtained with heparin-free equivalent fractions in both ELISA and RT-PCR assays indicates they should be appropriate for quantitative studies such as expression profiling at both the protein and nucleic acid level. CONCLUSIONS: The cost-effective protocols developed in this study could make heparinized, otherwise unusable, blood-derived collections suitable for analysis by ELISA and RT-PCR amplifications, among other analyses, enhancing the possibilities for studying valuable bio-banked heparinized human samples. PMID- 26280504 TI - The Bank of Biological Material (BBM) of the First Faculty of Medicine of Charles University in Prague, Czech Republic. PMID- 26280505 TI - The EUPRIM-Net Primates Biobank. PMID- 26280508 TI - Synthesis of quinoxalines or quinolin-8-amines from N-propargyl aniline derivatives employing tin and indium chlorides. AB - Pyrazino compounds such as quinoxalines are 1,4-diazines with widespread occurrence in nature. Quinolin-8-amines are isomerically related and valuable scaffolds in organic synthesis. Herein, we present intramolecular main group metal Lewis acid catalyzed formal hydroamination as well as hydroarylation methodology using mono-propargylated aromatic ortho-diamines. The annulations can be conducted utilizing equal aerobic conditions with either stannic chloride or indium(iii) chloride and represent primary examples for main group metal catalyzed 6-exo-dig and 6-endo-dig, respectively, cyclizations in such settings. Both types of reactions can also be utilized in a one-pot manner starting from ortho-nitro N-propargyl anilines using stoichiometric amounts SnCl2.2H2O or In powder. Mechanistic considerations are presented regarding the substituent depending regioselectivity. PMID- 26280510 TI - Whole-Genome Sequencing of Growth Hormone (GH)-Secreting Pituitary Adenomas. AB - CONTEXT: The somatic landscape of pituitary adenomas is largely unknown. Identification of somatic alterations aims at better understanding of tumor pathology. OBJECTIVE: The objective of the study was a genome-wide characterization of somatic single-nucleotide variants, structural variants, and copy-number aberrations in somatotropinomas. DESIGN AND SETTING: Whole-genome sequencing and single-nucleotide polymorphism array analyses were performed on 12 fresh-frozen somatotropinomas and their corresponding blood samples. All the coding somatic variants were confirmed by Sanger sequencing. PATIENTS: Studied tumors were somatotropinomas. Apart from one AIP mutation-positive patient, all cases were mutation negative for the established germline mutations associated with pituitary adenomas. INTERVENTION(S): There were no interventions. MAIN OUTCOME MEASURES: Somatic variants were identified with an established computational pipeline and filtered against germline data. Somatic copy number alteration analyses were performed using segmentation-based approaches. RESULTS: A genome-wide analysis revealed on average 129 somatic single-nucleotide variants per tumor. Further analysis of coding regions showed on average 2.3 single nucleotide variants per tumor. The only recurrent somatic events were the oncogenic GNAS mutation (p.Arg201Cys) and shared chromosome losses (chromosomes 1, 6, 13, 14, 15, 16, 18, 22). Analysis of somatic structural variants revealed one tumor with a complex chromosomal rearrangement. CONCLUSIONS: Somatotropinomas showed a low number of somatic genetic alterations. Whereas no novel recurrently mutated genes could be identified, the somatic landscape has potential to affect the Ca(2+) and ATP pathways known to be involved in the pituitary tumorigenesis. Further studies, eg, methylome and transcriptome analyses, are needed to investigate possible interplay between the recurrent chromosome losses and epigenetic factors. PMID- 26280509 TI - alpha-Klotho Expression in Human Tissues. AB - CONTEXT: alpha-Klotho has emerged as a powerful regulator of the aging process. To date, the expression profile of alpha-Klotho in human tissues is unknown, and its existence in some human tissue types is subject to much controversy. OBJECTIVE: This is the first study to characterize systemwide tissue expression of transmembrane alpha-Klotho in humans. We have employed next-generation targeted proteomic analysis using parallel reaction monitoring in parallel with conventional antibody-based methods to determine the expression and spatial distribution of human alpha-Klotho expression in health. RESULTS: The distribution of alpha-Klotho in human tissues from various organ systems, including arterial, epithelial, endocrine, reproductive, and neuronal tissues, was first identified by immunohistochemistry. Kidney tissues showed strong alpha Klotho expression, whereas liver did not reveal a detectable signal. These results were next confirmed by Western blotting of both whole tissues and primary cells. To validate our antibody-based results, alpha-Klotho-expressing tissues were subjected to parallel reaction monitoring mass spectrometry (data deposited at ProteomeXchange, PXD002775) identifying peptides specific for the full-length, transmembrane alpha-Klotho isoform. CONCLUSIONS: The data presented confirm alpha Klotho expression in the kidney tubule and in the artery and provide evidence of alpha-Klotho expression across organ systems and cell types that has not previously been described in humans. PMID- 26280511 TI - [Tumor-associated macrophages: Function and differentiation]. AB - Macrophages are important factors in the pathogenesis and prognosis of malignant tumors and represent a possible target for therapeutic intervention. Depending on the tumor entity and the prevalent polarization status, macrophages can be associated with a favorable or unfavorable clinical outcome. It is becoming clear, however, that the conventional definitions of M1 polarized tumor inhibitory and M2 polarized tumor promoting macrophages do not adequately reflect the heterogeneity and plasticity of macrophages. Macrophages can support tumor growth through direct interactions with the neoplastic cells, by promoting tissue remodeling and angiogenesis and by inhibiting local immune reactions. To achieve comparability of clinical studies, it will be necessary to reach a consensus nomenclature of macrophage polarization. Furthermore, methods for the quantitative characterization of macrophage populations in malignant tumors will have to be standardized. It is unlikely that single marker immunohistochemistry will be adequate in this context. In any case it is necessary to provide unequivocal information regarding the markers or marker combinations used. PMID- 26280514 TI - Retinal shows its true colours: photoisomerization action spectra of mobility selected isomers of the retinal protonated Schiff base. AB - Retinal is one of Nature's most important and widespread chromophores, exhibiting remarkable versatility in its function and spectral response, depending on its protein environment. Reliable spectroscopic and photochemical data for the isolated retinal molecule are essential for calibrating theoretical approaches that seek to model retinal's behaviour in complex protein environments. However, due to low densities and possible co-existence of multiple isomers, retinal is a challenging target for gas-phase investigations. Here, the photoisomerization behaviour of the trans isomer of the retinal protonated Schiff base (RPSB) is investigated in the gas phase by irradiating mobility-selected RPSB ions with tunable light in a tandem ion mobility spectrometer. trans RPSB ions are converted to single cis isomers and also more compact isomers through irradiation with visible light. The S1<- S0 photoisomerization action spectrum of trans RPSB, obtained by monitoring production of cis isomers as a function of wavelength, exhibits a single well-defined peak with a maximum at 618 +/- 5 nm. Corresponding action spectra of cis RPSB isomers exhibit broader peaks, conclusively demonstrating an isomeric dependence for the RPSB spectrum in the gas phase. PMID- 26280513 TI - Acute effects of ethanol on action potential and intracellular Ca(2+) transient in cardiac ventricular cells: a simulation study. AB - Alcohol consumption may result in electrocardiographic changes and arrhythmias, at least partly due to effects of ethanol on cardiac ionic currents. Contractility and intracellular Ca(2+) dynamics seem to be altered as well. In this study, we integrated the available (mostly animal) experimental data into previously published models of the rat and human ventricular myocytes to assess the share of ionic current components in ethanol-induced changes in AP configuration and cytosolic Ca(2+) transient in ventricular cardiomyocytes. The rat model reproduced well the experimentally observed changes in AP duration (APD) under ethanol (slight prolongation at 0.8 mM and shortening at >=8 mM). These changes were almost exclusively caused by the ethanol-induced alterations of I K1. The cytosolic Ca(2+) transient decreased gradually with the increasing ethanol concentration as a result of the ethanol-induced inhibition of I Ca. In the human model, ethanol produced a dose-dependent APD lengthening, dominated by ethanol effect on I Kr, the key repolarising current in human ventricles. This effect might contribute to the clinically observed proarrhythmic effects of ethanol in predisposed individuals. PMID- 26280512 TI - Sound transmission in porcine thorax through airway insonification. AB - Many pulmonary injuries and pathologies may lead to structural and functional changes in the lungs resulting in measurable sound transmission changes on the chest surface. Additionally, noninvasive imaging of externally driven mechanical wave motion in the chest (e.g., using magnetic resonance elastography) can provide information about lung structural property changes and, hence, may be of diagnostic value. In the present study, a comprehensive computational simulation (in silico) model was developed to simulate sound wave propagation in the airways, lung, and chest wall under normal and pneumothorax conditions. Experiments were carried out to validate the model. Here, sound waves with frequency content from 50 to 700 Hz were introduced into airways of five porcine subjects via an endotracheal tube, and transmitted waves were measured by scanning laser Doppler vibrometry at the chest wall surface. The computational model predictions of decreased sound transmission with pneumothorax were consistent with experimental measurements. The in silico model can also be used to visualize wave propagation inside and on the chest wall surface for other pulmonary pathologies, which may help in developing and interpreting diagnostic procedures that utilize sound and vibration. PMID- 26280515 TI - Arterial spin-labeling MR imaging of cerebral hemorrhages. AB - INTRODUCTION: The purpose of this study is to identify the characteristics of brain perfusion measured by arterial spin-labeling magnetic resonance imaging (ASL-MRI) in cerebral hemorrhages. METHODS: Brain blood flow values (CBF-ASL values) for cerebral and cerebellar hemispheres and segmented cerebral regions were measured by ASL-MRI in 19 putaminal hemorrhage patients and 20 thalamic hemorrhage patients in acute or subacute stages. We assessed the lateralities of CBF-ASL values and the relationships between CBF-ASL values and other imaging findings and clinical manifestations. RESULTS: Both the 19 putaminal hemorrhage patients and the 20 thalamic hemorrhage patients had significantly low CBF-ASL values of the contralateral cerebellum in subacute stage, suggesting that ASL-MRI might delineate crossed cerebellar diaschisis (CCD). Ipsilateral low CBF-ASL values were observed in frontal lobes and thalami with a putaminal hemorrhage and lentiform nuclei, temporal lobes, and parietal lobes with a thalamic hemorrhage, suggesting that ASL-MRI showed the ipsilateral cerebral diaschisis (ICD). In the putaminal hemorrhage patients, the hematoma volume negatively affected both the bilateral cerebellar and cerebral hemispheric CBF-ASL values. In the thalamic hemorrhage patients, a concomitant intraventricular hemorrhage caused low cerebral hemispheric CBF-ASL values. CONCLUSION: The use of ASL-MRI is sensitive to the perfusion abnormalities and could thus be helpful to estimate functional abnormalities in cerebral hemorrhage patients. PMID- 26280516 TI - MR image features predicting hemorrhagic transformation in acute cerebral infarction: a multimodal study. AB - INTRODUCTION: The aims of this study were to observe magnetic resonance imaging (MRI) features and the frequency of hemorrhagic transformation (HT) in patients with acute cerebral infarction and to identify the risk factors of HT. METHODS: We first performed multimodal MRI (anatomical, diffusion weighted, and susceptibility weighted) scans on 87 patients with acute cerebral infarction within 24 hours after symptom onset and documented the image findings. We then performed follow-up examinations 3 days to 2 weeks after the onset or whenever the conditions of the patients worsened within 3 days. We utilized univariate statistics to identify the correlations between HT and image features and used multivariate logistical regression to correct for confounding factors to determine relevant independent image features of HT. RESULTS: HT was observed in 17 out of total 87 patients (19.5 %). The infarct size (p = 0.021), cerebral microbleeds (CMBs) (p = 0.004), relative apparent diffusion (rADC) (p = 0.023), and venous anomalies (p = 0.000) were significantly related with HT in the univariate statistics. Multivariate analysis demonstrated that CMBs (odd ratio (OR) = 0.082; 95 % confidence interval (CI) = 0.011-0.597; p = 0.014), rADC (OR = 0.000; 95 % CI = 0.000-0.692; p = 0.041), and venous anomalies (OR = 0.066; 95 % CI = 0.011-0.403; p = 0.003) were independent risk factors for HT. CONCLUSIONS: The frequency of HT is 19.5 % in this study. CMBs, rADC, and venous anomalies are independent risk factors for HT of acute cerebral infarction. PMID- 26280517 TI - Comparative proteomic analysis of silkworm fat body after knocking out fibroin heavy chain gene: a novel insight into cross-talk between tissues. AB - Cross-talk between tissues plays key roles in development of organisms; however, there are few researches on cross-talk between tissues in insects. Our previous studies showed that the pupal body weight was elevated after knocking out the fibroin heavy chain gene (BmFib-H), whereas the gene specifically expressed in silk glands of silkworm. Hence, the mutant is a good material for studying the cross-talk between tissues. It is considered that the fat body of silkworm during larval stage is used to store nutrients for pupal development. Herein, comparative proteomic of fat body on the 5th day of fifth instar was performed between BmFib-H gene knock-out Bombyx mori line (FGKO) and its wide-type Dazao. These results revealed that a single gene knock-out in silk gland triggered large scale metabolic pathways changes in fat body. The levels of proteins involved in glycolysis/gluconeogenesis, pentose phosphate pathway, and glycine-serine biosynthetic pathway were down-regulated in the FGKO fat body. In contrast, the abundances of many proteins participating in protein synthesis, including ribosomal proteins, eukaryotic translation initiation factor, and elongation factor, were up-regulated. Moreover, the concentrations of glycogen and proteins in the FGKO fat body were greatly increased. These findings provided a novel insight into the cross-talk between silk gland and fat body in silkworm, and the presence of cross-talk between silk gland and fat body could regulate the redistribution of nutrients in the FGKO fat body leading to the increase of the pupal weight. PMID- 26280518 TI - MmoSTI restriction endonuclease, isolated from Morganella morganii infecting a tropical moth, Actias selene, cleaving 5'-|CCNGG-3' sequences. AB - A type II restriction endonuclease, MmoSTI, from the pathogenic bacterium Morganella morganii infecting a tropical moth, Actias selene, has been detected and biochemically characterized, as a potential etiological differentiation factor. The described REase recognizes interrupted palindromes, i.e., 5'-CCNGG-3' sequences and cleaves DNA leaving 5-nucleotide (nt) long, single-stranded (ss), 5'-cohesive ends, which was determined by three complementary methods: (i) cleavage of custom and standard DNA substrates, (ii) run-off sequencing of cleavage products, and (iii) shotgun cloning and sequencing of bacteriophage lambda (lambda) DNA digested with MmoSTI. MmoSTI, the first 5'-CCNGG-3' REase characterized from M. morganii, is a neoschizomer of ScrFI, which cleaves DNA leaving 1-nt long, ss, 5'-cohesive ends. It is a high-frequency cutter and can be isolated from easily cultured bacteria, thus it can potentially serve as a tool for DNA manipulations. PMID- 26280519 TI - An Experience with Auricular Free Flap Epiglottis Reconstruction after Supraglottic Laryngectomy. PMID- 26280520 TI - Decellularized Nerves for Upper Limb Nerve Reconstruction: A Systematic Review of Functional Outcomes. AB - BACKGROUND: This is a systematic review for evaluating the evidence for functional outcomes after decellularized nerve use in clinical setting. Decellularized nerves are allografts whose antigenic components have been removed, leaving only a scaffold that promotes the full regeneration of axons. METHODS: Literature research was performed using the PubMed/MEDLINE database for English language studies with the keywords "decellularized nerve" and "processed nerve allograft." Inclusion criteria were prospective and retrospective case reviews in clinical settings. Exclusion criteria were case reports and case series. RESULTS: We retrieved six level VIII studies and one level VI study (classified according to the Jovell and Navarro-Rubio scale) with a total of 131 reconstructions. The basic data ranges of the studies were as follows: patient age, 18 to 86 years; duration between initial injury and nerve reconstruction procedure, 8 hours to 4 years; and follow-up period, 40 days to 2 years. The maximum lengths of the nerve gap for chemically washed decellularized nerves and cryopreserved decellularized nerves were 50 and 100 mm, respectively. Quantitatively, the functional outcome ranges were as follows: static two-point discrimination, 3 to 5 mm; and moving two-point discrimination, 2 to 15 mm. For motor assessment, all patients had a > M3 Medical Research Council score. It is also important to notice that a large variability occurs in almost every factor in the reviewed studies. CONCLUSION: Our study is the first to summarize the clinical results of decellularized nerves. Decellularized nerves have been used to bridge nerve gaps ranging from 5 to 100 mm with associated satisfactory outcomes in static and moving two-point discriminations. PMID- 26280521 TI - Use of Polymethyl Methacrylate-Based Cement for Cosmetic Correction of Donor-Site Defect following Transposition of Temporalis Myofascial Flap and Evaluation of Results after Adjuvant Radiotherapy. AB - BACKGROUND: Temporalis myofascial flap is a versatile flap for reconstruction of the oral cavity defects, but results in an esthetically compromised deformity at the donor site. We used polymethyl methacrylate (PMMA) cement to correct the volume loss defect caused by temporalis myofascial flap and evaluated its results before and after adjuvant radiotherapy. METHODS: We discuss our experience of using PMMA cement to augment donor-site deformity in 25 patients (17 males, 8 females) between years 2005 and 2009. The primary defect was a result of the ablative surgery for squamous cell carcinoma of the upper alveolar and the buccoalveolar sulcus. A modified curved hemicoronal incision was used as an access for better cosmetic outcome. The volume of cement required was decided during the surgery. RESULTS: All patients are in regular follow-up, alive and free of complications at implant site, except one patient who developed wound dehiscence. The condition of the implant was evaluated by postoperative computed tomographic scan, repeated after adjuvant radiotherapy in cases required. There were no radiation-induced changes in the contour and volume of the implants. Cosmetic result of the implant was reported satisfactory by the patients postoperatively. CONCLUSION: Restoration of the temporal area defect after the temporalis myofascial flap harvest with the use of PMMA cement is an easy and safe method, with excellent esthetic results. The implant is stable and resistant to any changes in contour and loss of volume even after adjuvant radiotherapy, with no added morbidity to the patients. PMID- 26280523 TI - Interleukin 28B.rs12979860 genotype does not affect hepatitis C viral load in Egyptians with genotype 4 chronic infection. AB - Several host and viral factors affect the natural history of Hepatitis C Virus (HCV) infection. Interleukin 28B (IL28B).rs12979860 single nucleotide polymorphism (SNP) was found to predict viral clearance with and without therapy. Subjects with the CC (favorable) genotype of IL28B.rs12979860 were more likely to spontaneously clear the infection and respond favorably to therapy. These data suggest that subjects with the "favorable" CC genotype might have a lower viral load when compared to those with the "unfavorable" TT genotype. Therefore, we examined the effect of IL28B.rs12979860 SNP on HCV viral load and clearance among HCV-infected Egyptians. This cross sectional study was conducted on 375 HCV antibody-positive subjects. Detection and quantification of HCV-RNA was determined by RT-PCR. IL28B.rs12979860 genotyping was performed using SYBR green real-time PCR and specific primers. Of 375 HCV-antibody positive subjects, 239 (63.7%) had chronic HCV infection while the remaining 136 (36.3%) subjects had spontaneously cleared the virus. The frequency of IL28-B CC, CT, and TT genotypes among spontaneous resolvers were 54.4%, 39.0%, and 6.6% while among the chronically infected subjects, they were 31.4%, 49.8%, and 18.8%, respectively. As expected, IL28 genotype predicted spontaneous HCV clearance (p < 0.001). The average HCV viral loads were 1.5 +/- 0.69 x 10(6), 0.62 +/- 0.11 x 10(6) and 0.51 +/- 0.14 x 10(6) IU/ml among chronic subjects with the IL28B.rs12979860 CC, CT and TT genotypes, respectively (p > 0.05). In conclusion, our results show that IL28B.rs12979860 genotype does not affect viral load among chronic HCV infected Egyptians. These findings further confirm the complexity of viral host interactions in determining HCV infection outcome. PMID- 26280524 TI - Development of novel antibodies against non-structural proteins nsP1, nsP3 and nsP4 of chikungunya virus: potential use in basic research. AB - Chikungunya virus (CHIKV) has reemerged recently as an important pathogen, causing several large epidemics worldwide. This necessitates the development of better reagents to understand its biology and to establish effective and safe control measures. The present study describes the development and characterization of polyclonal antibodies (pAbs) against synthetic peptides of CHIKV non-structural proteins (nsPs; nsP1, nsP3 and nsP4). The reactivity of these pAbs was demonstrated by ELISA and Western blot. Additionally, in vitro infection studies in a mammalian system confirmed that these pAbs are highly sensitive and specific for CHIKV nsPs, as these proteins were detected very early during viral replication. Homology analysis of the selected epitope sequences revealed that they are conserved among all of the CHIKV strains of different genotypes, while comparison with other alphavirus sequences showed that none of them are 100% identical to the epitope sequences (except Onyong-nyong and Igbo Ora viruses, which show 100% identity to the nsP4 epitope). Interestingly, two different forms of CHIKV nsP1 and three different forms of nsP3 were detected in Western blot analysis during infection; however, further experimental investigations are required to confirm their identity. Also, the use of these antibodies demonstrated faster and enhanced expression profiles of all CHIKV nsPs in 2006 Indian outbreak strains when compared to the CHIKV prototype strain, suggesting the epidemic potential of the 2006 isolate. Accordingly, it can be suggested that the pAbs reported in this study can be used as sensitive and specific tools for experimental investigations of CHIKV replication and infection. PMID- 26280522 TI - Neuroprotective efficacy of naringin on 3-nitropropionic acid-induced mitochondrial dysfunction through the modulation of Nrf2 signaling pathway in PC12 cells. AB - Oxidative stress and mitochondrial dysfunction are implicated in neuronal apoptosis associated with Huntington's disease. Naringin is the flavanone present in grapefruit and related citrus species possess diverse pharmacological and therapeutic properties including antioxidant, anti-apoptotic, and neuroprotective properties. The aim of this study was to investigate the protective effect of naringin on 3-nitropropionic acid (3-NP)-induced neurotoxicity in pheochromocytoma cells (PC12) cells and to explore its mechanism of action. Naringin protects PC12 cells from 3-NP neurotoxicity, as evaluated the by cell viability assays. The lactate dehydrogenase release was decreased upon naringin treatment in 3-NP-induced PC12 cells. Naringin treatment enhances the antioxidant defense by increasing the activities of enzymatic antioxidants and the level of reduced glutathione. The increase in levels of reactive oxygen species and lipid peroxidation induced by 3-NP were significantly decreased by naringin. PC12 cells induced with 3-NP showed decrease in the mitochondrial membrane potential and mitochondrial respiratory complex enzymes, succinate dehydrogenase and cytochrome c oxidase activities, and it was significantly altered to near normal upon naringin treatment. Naringin reduced the 3-NP-induced apoptosis through the modulation in expressions of B-cell lymphoma 2 and Bcl-2-associated X protein. Further, naringin enhances the nuclear translocation of Nrf2 and induces the NAD(P)H: quinone oxidoreductase-1 and Heme oxygenase-1 expressions through the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway. Taken together, the above findings suggest that naringin augments cellular antioxidant defense capacity and reduces the 3-NP-induced neurotoxicity in PC12 cells through the PI 3K/Akt-dependent Nrf2 activation in PC12 cells. PMID- 26280525 TI - Novel method for genotyping clinical herpes simplex virus type 1 isolates. AB - Up to now, three distinct genotypes, A, B and C, of herpes simplex virus type 1 (HSV-1), based on polymorphisms in the US4 and US7 genes, have been reported. Here, we propose to include an additional polymorphism of the US2 gene. The refined genotyping method was validated using 423 clinical isolates from patients with different HSV-1 diseases. The proportions of three US2 genotypes were A, 46.6%; B, 23.2%; and C, 30.2 %. Genotype A of US2 and US4/US7 showed a highly significant correlation. In addition, the frequency of genotype A was significantly higher in women than in men with herpes labialis. PMID- 26280526 TI - Sewage surveillance reveals the presence of canine GVII norovirus and canine astrovirus in Uruguay. AB - Canine norovirus (NoV) and astrovirus (AstV) were studied in 20 domestic sewage samples collected in two cities in Uruguay. Four samples were characterized as canine AstV after phylogenetic analysis clustering with strains detected in Italy and Brazil in 2008 and 2012, respectively. One sample was characterized as canine NoV and clustered with a strain detected in Hong Kong and recently classified as GVII. This study shows the occurrence of a canine NoV GVII strain for the first time in the American continent and also warns about possible zoonotic infection, since canine strains were detected in domestic sewage. PMID- 26280527 TI - Investigating the optimal preconception TSH range for patients undergoing IVF when controlling for embryo quality. AB - PURPOSE: The ideal thyroid-stimulating hormone (TSH) range for infertile women attempting conception has not been determined. Current recommendations include optimizing the preconception TSH value to <=2.5 mIU/L, which is the established goal for pregnant women. The aim of this study was to determine if there is a distinct range of TSH <=2.5 mIU/L for infertile women undergoing in vitro fertilization (IVF) that improves reproductive outcomes. METHODS: One thousand five hundred ninety-nine euploid blastocyst transfer cycles were evaluated in which TSH measurements were obtained 8 days after embryo transfer. Only euploid embryo transfers were included in an effort to control for embryo quality. Patients were separated into TSH groups utilizing 0.5 mIU/L increments. Implantation, live birth, and miscarriage rates among the TSH groups were compared. Outcomes for individuals on thyroid hormone supplementation and those not requiring supplementation were evaluated. RESULTS: There was no difference in implantation (p = 0.56), live birth (p = 0.36), or miscarriage rates (p = 0.10) between TSH groups. Receiver operating characteristic (ROC) curves for implantation, live birth, and miscarriage approached the line of no discrimination, signifying that there is no value of TSH within the recommended range for pregnancy (<=2.5 mIU/L) that predicts IVF outcomes better than other values in this range. Live birth rates for patients requiring thyroid hormone supplementation and those not on medication were similar (p = 0.86). CONCLUSIONS: The recommended TSH range for pregnancy (<=2.5 mIU/L) may be applied to infertile patients attempting conception without a need for further adjustment. PMID- 26280528 TI - Solid-state NMR sequential assignments of the N-terminal domain of HpDnaB helicase. AB - We present solid-state NMR assignments of the N-terminal domain of the DnaB helicase from Helicobacter pylori (153 residues) in its microcrystalline form. We use a sequential resonance assignment strategy based on three-dimensional NMR experiments. The resonance assignments obtained are compared with automated resonance assignments computed with the ssFLYA algorithm. An analysis of the (13)C secondary chemical shifts determines the position of the secondary structure elements in this alpha-helical protein. PMID- 26280529 TI - Sequence-specific 1H, 15N, and 13C resonance assignments of the autophagy-related protein LC3C. AB - Autophagy is a versatile catabolic pathway for lysosomal degradation of cytoplasmic material. While the phenomenological and molecular characteristics of autophagic non-selective (bulk) decomposition have been investigated for decades, the focus of interest is increasingly shifting towards the selective mechanisms of autophagy. Both, selective as well as bulk autophagy critically depend on ubiquitin-like modifiers belonging to the Atg8 (autophagy-related 8) protein family. During evolution, Atg8 has diversified into eight different human genes. While all human homologues participate in the formation of autophagosomal membrane compartments, microtubule-associated protein light chain 3C (LC3C) additionally plays a unique role in selective autophagic clearance of intracellular pathogens (xenophagy), which relies on specific protein-protein recognition events mediated by conserved motifs. The sequence-specific (1)H, (15)N, and (13)C resonance assignments presented here form the stepping stone to investigate the high-resolution structure and dynamics of LC3C and to delineate LC3C's complex network of molecular interactions with the autophagic machinery by NMR spectroscopy. PMID- 26280530 TI - Alcohol Expectancies and Inhibition Conflict as Moderators of the Alcohol Unprotected Sex Relationship: Event-Level Findings from a Daily Diary Study Among Individuals Living with HIV in Cape Town, South Africa. AB - Literature from sub-Saharan Africa and elsewhere supports a global association between alcohol and HIV risk. However, more rigorous studies using multiple event level methods find mixed support for this association, suggesting the importance of examining potential moderators of this relationship. The present study explores the assumptions of alcohol expectancy theory and alcohol myopia theory as possible moderators that help elucidate the circumstances under which alcohol may affect individuals' ability to use a condom. Participants were 82 individuals (58 women, 24 men) living with HIV who completed daily phone interviews for 42 days which assessed daily sexual behavior and alcohol consumption. Logistic generalized estimating equation models were used to examine the potential moderating effects of inhibition conflict and sex-related alcohol outcome expectancies. The data provided some support for both theories and in some cases the moderation effects were stronger when both partners consumed alcohol. PMID- 26280532 TI - Recruitment and activation of the ATM kinase in the absence of DNA-damage sensors. AB - Two kinases, ATM and DNA-PKcs, control rapid responses to DNA double-strand breaks (DSBs). The paradigm for ATM control is recruitment and activation by the Mre11-Rad50-NBS1 (MRN) sensor complex, whereas DNA-PKcs requires the sensor Ku (Ku70-Ku80). Using mouse cells containing targeted mutant alleles of Mre11 (Mre11a) and/or Ku70 (Xrcc6), together with pharmacologic kinase inhibition, we demonstrate that ATM can be activated by DSBs in the absence of MRN. When MRN is deficient, DNA-PKcs efficiently substitutes for ATM in facilitating local chromatin responses. In the absence of both MRN and Ku, ATM is recruited to chromatin, where it phosphorylates H2AX and triggers the G2-M cell-cycle checkpoint, but the DNA-repair functions of MRN are not restored. These results suggest that, in contrast to straightforward recruitment and activation by MRN, a complex interplay between sensors has a substantial role in ATM control. PMID- 26280533 TI - Recognition of the bacterial alarmone ZMP through long-distance association of two RNA subdomains. AB - The bacterial alarmone 5-aminoimidazole-4-carboxamide riboside 5'-triphosphate (AICAR triphosphate or ZTP), derived from the monophosphorylated purine precursor ZMP, accumulates during folate starvation. ZTP regulates genes involved in purine and folate metabolism through a cognate riboswitch. The linker connecting this riboswitch's two subdomains varies in length by over 100 nucleotides. We report the cocrystal structure of the Fusobacterium ulcerans riboswitch bound to ZMP, which spans the two subdomains whose interface also comprises a pseudoknot and ribose zipper. The riboswitch recognizes the carboxamide oxygen of ZMP through an unprecedented inner-sphere coordination with a Mg(2+) ion. We show that the affinity of the riboswitch for ZMP is modulated by the linker length. Notably, ZMP can simultaneously bind to the two subdomains even when they are synthesized as separate RNAs. The ZTP riboswitch demonstrates how specific small-molecule binding can drive association of distant noncoding-RNA domains to regulate gene expression. PMID- 26280531 TI - Structure and mechanism of activity-based inhibition of the EGF receptor by Mig6. AB - Mig6 is a feedback inhibitor that directly binds, inhibits and drives internalization of ErbB-family receptors. Mig6 selectively targets activated receptors. Here we found that the epidermal growth factor receptor (EGFR) phosphorylates Mig6 on Y394 and that this phosphorylation is primed by prior phosphorylation of an adjacent residue, Y395, by Src. Crystal structures of human EGFR-Mig6 complexes reveal the structural basis for enhanced phosphorylation of primed Mig6 and show how Mig6 rearranges after phosphorylation by EGFR to effectively irreversibly inhibit the same receptor that catalyzed its phosphorylation. This dual phosphorylation site allows Mig6 to inactivate EGFR in a manner that requires activation of the target receptor and that can be modulated by Src. Loss of Mig6 is a driving event in human cancer; analysis of 1,057 gliomas reveals frequent focal deletions of ERRFI1, the gene that encodes Mig6, in EGFR-amplified glioblastomas. PMID- 26280534 TI - Iron Supplementation in Iron-Replete and Nonanemic Pregnant Women in Tanzania: A Randomized Clinical Trial. AB - IMPORTANCE: Anemia is common in pregnancy and increases the risk of adverse outcomes. Iron deficiency is a leading cause of anemia in sub-Saharan Africa, and iron supplementation is the standard of care during pregnancy; however, recent trials among children have raised concerns regarding the safety of iron supplementation in malaria-endemic regions. There is limited evidence on the safety of iron supplementation during pregnancy in these areas. OBJECTIVE: To evaluate the safety and efficacy of iron supplementation during pregnancy in a malaria-endemic region. DESIGN, SETTING, AND PARTICIPANTS: We conducted a randomized, double-blind, placebo-controlled clinical trial among pregnant women presenting for antenatal care in Dar es Salaam, Tanzania, from September 28, 2010, through October 4, 2012. Iron-replete, nonanemic women were eligible if they were uninfected with human immunodeficiency virus, primigravidae or secundigravidae, and at or before 27 weeks of gestation. Screening of 21,316 women continued until the target enrollment of 1500 was reached. Analyses followed the intent-to-treat principle and included all randomized participants. INTERVENTIONS: Participants were randomized to receive 60 mg of iron or placebo, returning every 4 weeks for standard prenatal care, including malaria screening, prophylaxis with the combination of sulfadoxine and pyrimethamine, and treatment, as needed. MAIN OUTCOMES AND MEASURES: The primary outcomes were placental malaria, maternal hemoglobin level at delivery, and birth weight. RESULTS: Among 1500 study participants (750 randomized for each group), 731 in iron group and 738 in placebo group had known birth outcomes and 493 in iron group and 510 in placebo group had placental samples included in the analysis. Maternal characteristics were similar at baseline in the iron and placebo groups, and 1354 (91.7%) used malaria control measures. The risk of placental malaria was not increased by maternal iron supplementation (relative risk [RR], 1.03; 95% CI, 0.65-1.65), and iron supplementation did not significantly affect birth weight (3155 vs 3137 g, P = .89). Compared with placebo, iron supplementation significantly improved the mean increase from baseline to delivery for hemoglobin (0.1 vs -0.7 g/dL, P < .001) and serum ferritin (41.3 vs 11.3 ug/L, P < .001). Iron supplementation significantly decreased the risk of anemia at delivery by 40% (RR, 0.60; 95% CI, 0.51-0.71) but not severe anemia (RR, 0.68; 95% CI, 0.41 1.14). Iron supplementation significantly reduced the risk of maternal iron deficiency at delivery by 52% (RR, 0.48; 95% CI, 0.32-0.70) and the risk of iron deficiency anemia by 66% (RR, 0.34; 95% CI, 0.19-0.62). CONCLUSIONS AND RELEVANCE: Prenatal iron supplementation among iron-replete, nonanemic women was not associated with an increased risk of placental malaria or other adverse events in the context of good malaria control. Participants receiving supplementation had improved hematologic and iron status at delivery compared with the placebo group. These findings provide support for continued administration of iron during pregnancy in malaria-endemic regions. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01119612. PMID- 26280536 TI - Deubiquitylase OTUD3 regulates PTEN stability and suppresses tumorigenesis. AB - PTEN is one of the most frequently mutated tumour suppressors and reduction in PTEN protein stability also plays a role in tumorigenesis. Although several ubiquitin ligases for PTEN have been identified, the deubiquitylase for de polyubiquitylation and stabilization of PTEN is less defined. Here, we report OTUD3 as a deubiquitylase of PTEN. OTUD3 interacts with, de-polyubiquitylates and stabilizes PTEN. Depletion of OTUD3 leads to the activation of Akt signalling, induction of cellular transformation and cancer metastasis. OTUD3 transgenic mice exhibit higher levels of the PTEN protein and are less prone to tumorigenesis. Reduction of OTUD3 expression, concomitant with decreased PTEN abundance, correlates with human breast cancer progression. Furthermore, we identified loss of-function OTUD3 mutations in human cancers, which either abolish OTUD3 catalytic activity or attenuate the interaction with PTEN. These findings demonstrate that OTUD3 is an essential regulator of PTEN and that the OTUD3-PTEN signalling axis plays a critical role in tumour suppression. PMID- 26280535 TI - mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype. AB - Senescent cells secrete a combination of factors collectively known as the senescence-associated secretory phenotype (SASP). The SASP reinforces senescence and activates an immune surveillance response, but it can also show pro tumorigenic properties and contribute to age-related pathologies. In a drug screen to find new SASP regulators, we uncovered the mTOR inhibitor rapamycin as a potent SASP suppressor. Here we report a mechanism by which mTOR controls the SASP by differentially regulating the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1. In turn, MAPKAPK2 phosphorylates the RNA-binding protein ZFP36L1 during senescence, inhibiting its ability to degrade the transcripts of numerous SASP components. Consequently, mTOR inhibition or constitutive activation of ZFP36L1 impairs the non-cell-autonomous effects of senescent cells in both tumour-suppressive and tumour-promoting contexts. Altogether, our results place regulation of the SASP as a key mechanism by which mTOR could influence cancer, age-related diseases and immune responses. PMID- 26280537 TI - Secreted and O-GlcNAcylated MIF binds to the human EGF receptor and inhibits its activation. AB - Activation of epidermal growth factor receptor (EGFR), which occurs in many types of tumour, promotes tumour progression. However, no extracellular antagonist of human EGFR has been identified. We found that human macrophage migration inhibitory factor (MIF) is O-GlcNAcylated at Ser 112/Thr 113 at its carboxy terminus. The naturally secreted and O-GlcNAcylated MIF binds to EGFR, thereby inhibiting the binding of EGF to EGFR and EGF-induced EGFR activation, phosphorylation of ERK and c-Jun, cell invasion, proliferation and brain tumour formation. Activation of EGFR through mutation or its ligand binding enhances the secretion of MMP13, which degrades extracellular MIF, and results in abrogation of the negative regulation of MIF on EGFR. The finding that EGFR activation downregulates its antagonist in the tumour microenvironment represents an important feedforward mechanism for human tumour cells to enhance EGFR signalling and promote tumorigenesis. PMID- 26280539 TI - Spectral wide-field microscopic fluorescence resonance energy transfer imaging in live cells. AB - With its precise, sensitive, and nondestructive features, spectral unmixing-based fluorescence resonance energy transfer (FRET) microscopy has been widely applied to visualize intracellular biological events. In this report, we set up a spectral wide-field microscopic FRET imaging system by integrating a varispec liquid crystal tunable filter into a wide-field microscope for quantitative FRET measurement in living cells. We implemented a representative emission-spectral unmixing-based FRET measurement method on this platform to simultaneously acquire pixel-to-pixel images of both FRET efficiency (E ) and acceptor-to-donor concentration ratio (R C ) in living HepG2 cells expressing fusion proteins in the presence or absence of free donors and acceptors and obtained consistent results with other instruments and methods. This stable and low-cost spectral wide-field microscopic FRET imaging system provides a new toolbox for imaging molecular events with high spatial resolution in living cells. PMID- 26280538 TI - Distinct regulatory mechanisms governing embryonic versus adult adipocyte maturation. AB - Pathological expansion of adipose tissue contributes to the metabolic syndrome. Distinct depots develop at various times under different physiological conditions. The transcriptional cascade mediating adipogenesis is established in vitro, and centres around a core program involving PPARgamma and C/EBPalpha. We developed an inducible, adipocyte-specific knockout system to probe the requirement of key adipogenic transcription factors at various stages of adipogenesis in vivo. C/EBPalpha is essential for all white adipogenic conditions in the adult stage, such as adipose tissue regeneration, adipogenesis in muscle and unhealthy expansion of white adipose tissue during high-fat feeding or due to leptin deficiency. Surprisingly, terminal embryonic adipogenesis is fully C/EBPalpha independent, but does however depend on PPARgamma; cold-induced beige adipogenesis is also C/EBPalpha independent. Moreover, C/EBPalpha is not vital for adipocyte survival in the adult stage. We reveal a surprising diversity of transcriptional signals required at different stages of adipogenesis in vivo. PMID- 26280540 TI - Three-dimensional image analytical detection of intussusceptive pillars in murine lung. AB - A variety of diseases can lead to loss of lung tissue. Currently, this can be treated only symptomatically. In mice, a complete compensatory lung growth within 21 days after resection of the left lung can be observed. Understanding and transferring this concept of compensatory lung growth to humans would greatly improve therapeutic options. Lung growth is always accompanied by a process called angiogenesis forming new capillary blood vessels from preexisting ones. Among the processes during lung growth, the formation of transluminal tissue pillars within the capillary vessels (intussusceptive pillars) is observed. Therefore, pillars can be understood as an indicator for active angiogenesis and microvascular remodelling. Thus, their detection is very valuable when aiming at characterization of compensatory lung growth. In a vascular corrosion cast, these pillars appear as small holes that pierce the vessels. So far, pillars were detected visually only based on 2D images. Our approach relies on high-resolution synchrotron microcomputed tomographic images. With a voxel size of 370 nm we exploit the spatial information provided by this imaging technique and present the first algorithm to semiautomatically detect intussusceptive pillars. An at least semiautomatic detection is essential in lung research, as manual pillar detection is not feasible due to the complexity and size of the 3D structure. Using our algorithm, several thousands of pillars can be detected and subsequently analysed, e.g. regarding their spatial arrangement, size and shape with an acceptable amount of human interaction. In this paper, we apply our novel pillar detection algorithm to compute pillar densities of different specimens. These are prepared such that they show different growing states. Comparing the corresponding pillar densities allows to investigate lung growth over time. PMID- 26280541 TI - Concurrent Use of Low-Dose Aspirin and Omega-3 Fatty Acids and Risk of Upper Gastrointestinal Complications: A Cohort Study with Nested Case-Control Analysis. AB - The risk of upper gastrointestinal complications (UGIC) due to low-dose aspirin (LDA) can be further increased by the concurrent exposure to other antithrombotic agents. Little is known on the combined therapy with LDA and medications containing omega-3 (OM3) fatty acids, which also exert antiplatelet activity. The aim of this study was to investigate the risk of UGIC in patients exposed to LDA OM3 combination. The Italian Health Search IMS Health Longitudinal Patients Database was used to perform a population-based cohort study. Patients aged >=18 years with cardio- or cerebrovascular ischaemic disease recorded between 2002 and 2012 (cohort entry) were selected. All UGIC cases (index date) observed up to December 2013 were identified. According to a nested case-control analysis, up to 10 controls were matched to each case on age, sex and calendar period. The risk of UGIC was investigated among current (up to 30 days preceding index date), recent (31-60 days) and past users (61-365 days) of the LDA-OM3 combination. Exposure assessment was lagged by 30 days to minimize reverse causation. Additionally, a duration-response analysis was performed. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Non-users of the LDA-OM3 combination were the reference category. Current (OR = 0.66; 95% CI: 0.44-1.00), recent (OR = 0.83; 95% CI: 0.52-1.33) and past users (OR = 0.81; 95% CI: 0.57-1.15) did not statistically significantly increase the risk of UGIC. No duration-response relationship was found. Our results suggest that LDA-OM3 combination therapy does not affect the UGIC risk in patients with cardio- or cerebrovascular ischaemic diseases. Given the novelty of these findings, further studies are needed. PMID- 26280542 TI - Computational Study and Kinetic Analysis of the Aminolysis of Thiolactones. AB - The aminolysis of three differently alpha-substituted gamma-thiolactones (C4H5OSX, X = H, NH2, and NH(CO)CH3) is modeled based on CBS-QB3 calculated free energies corrected for solvation using COSMO-RS. For the first time, quantitative kinetic and thermodynamic data are provided for the concerted path and the stepwise path over a neutral tetrahedral intermediate. These paths can take place via an unassisted, an amine-assisted, or a thiol-assisted mechanism. Amine assistance lowers the free energy barriers along both paths, while thiol assistance only lowers the formation of the neutral tetrahedral intermediate. Based on the ab initio calculated rate coefficients, a kinetic model is constructed that is able to reliably describe experimental observations for the aminolysis of N-acetyl-dl-homocysteine thiolactone with n-butylamine in THF and CHCl3. Reaction path analysis shows that for all conditions relevant for applications in polymer synthesis and postpolymer modification, an assisted stepwise mechanism is operative in which the formation of the neutral tetrahedral intermediate is rate-determining and which is mainly amine-assisted at low conversions and thiol-assisted at high conversions. PMID- 26280543 TI - Comparative analysis of virulence genes, antibiotic resistance and gyrB-based phylogeny of motile Aeromonas species isolates from Nile tilapia and domestic fowl. AB - The nucleotide sequence analysis of the gyrB gene indicated that the fish Aeromonas spp. isolates could be identified as Aeromonas hydrophila and Aeromonas veronii biovar sobria, whereas chicken Aeromonas spp. isolates identified as Aeromonas caviae. PCR data revealed the presence of Lip, Ser, Aer, ACT and CAI genes in fish Aer. hydrophila isolates, ACT, CAI and Aer genes in fish Aer. veronii bv sobria isolates and Ser and CAI genes in chicken Aer. caviae isolates. All chicken isolates showed variable resistance against all 12 tested antibiotic discs except for cefotaxime, nitrofurantoin, chloramphenicol and ciprofloxacin, only one isolate showed resistance to chloramphenicol and ciprofloxacin. Fish Aeromonads were sensitive to all tested antibiotic discs except amoxicillin, ampicillin-sulbactam and streptomycin. SIGNIFICANCE AND IMPACT OF THE STUDY: Many integrated fish farms depend on the application of poultry droppings/litter which served as a direct feed for the fish and also acted as pond fertilizers. The application of untreated poultry manure exerts an additional pressure on the microbial world of the fish's environment. Aeromonas species are one of the common bacteria that infect both fish and chicken. The aim of this study was to compare the phenotypic traits and genetic relatedness of aeromonads isolated from two diverse hosts (terrestrial and aquatic), and to investigate if untreated manure possibly enhances Aeromonas dissemination among cohabitant fish with special reference to virulence genes and antibiotic resistant traits. PMID- 26280545 TI - Fabrication of Collagen Gel Hollow Fibers by Covalent Cross-Linking for Construction of Bioengineering Renal Tubules. AB - Collagen, the most used natural biomacromolecule, has been extensively utilized to make scaffolds for cell cultures in tissue engineering, but has never been fabricated into the configuration of a hollow fiber (HF) for cell culture due to its poor mechanical properties. In this study, renal tubular cell-laden collagen hollow fiber (Col HF) was fabricated by dissolving sacrificial Ca-alginate cores from collagen shells strengthened by carbodiimide cross-linking. The inner/outer diameters of the Col HF were precisely controlled by the flow rates of core alginate/shell collagen solution in the microfluidic device. As found, the renal tubular cells self-assembled into renal tubules with diameters of 50-200 MUm post to the culture in Col HF for 10 days. According to the 3D reconstructed confocal images or HE staining, the renal cells appeared as a tight tubular monolayer on the Col HF inner surface, sustaining more 3D cell morphology than the cell layer on the 2D flat collagen gel surface. Moreover, compared with the cultures in either a Transwell or polymer HF membrane, the renal tubules in Col HF exhibited at least 1-fold higher activity on brush border enzymes of alkaline phosphatase and gamma-glutamyltransferase, consistent with their gene expressions. The enhancement occurred similarly on multidrug resistance protein 2 and glucose uptake. Such bioengineered renal tubules in Col HF will present great potential as alternatives to synthetic HF in both clinical use and pharmaceutical investigation. PMID- 26280544 TI - Allergens in veterinary medicine. AB - Allergic diseases in animals are increasingly gaining importance in veterinary practice and as research models. For intradermal testing and allergen immunotherapy, a good knowledge of relevant allergens for the individual species is of great importance. Currently, the knowledge about relevant veterinary allergens is based on sensitization rates identified by intradermal testing or serum testing for allergen-specific IgE; crude extracts are the basis for most evaluations. Only a few studies provide evidence about the molecular structure of (particularly) dust mite, insect and mould allergens in dogs and horses, respectively. In those species, some major allergens differ from those in humans. This position paper summarizes the current knowledge about relevant allergens in dogs, cats and horses. PMID- 26280546 TI - Tongue Volume Influences Lowest Oxygen Saturation but Not Apnea-Hypopnea Index in Obstructive Sleep Apnea. AB - OBJECTIVES: The aim of this study was to identify correlations between sleep apnea severity and tongue volume or posterior airway space measured via three dimensional reconstruction of volumetric computerized tomography (CT) images in patients with obstructive sleep apnea (OSA) for use in predicting OSA severity and in surgical treatment. We also assessed associations between tongue volume and Mallampati score. METHODS: Snoring/OSA male patients (n = 64) who underwent polysomnography, cephalometry, and CT scans were enrolled in this retrospective study. OSA was diagnosed when the apnea-hypopnea index (AHI) was greater than 5 (mild 5-14; moderate 15-29; severe>30). The patients were also categorized into the normal-mild group (n = 22) and the moderate-severe group (n = 42). Using volumetric CT images with the three-dimensional reconstruction technique, the volume of the tongue, posterior airway space volume, and intra-mandibular space were measured. The volumes, polysomnographic parameters, and physical examination findings were compared, and independent factors that are related to OSA were analysed. RESULTS: No associations between tongue volume or posterior airway space and the AHI were observed. However, multivariate linear analyses showed that tongue volume had significantly negative association with lowest O2 saturation (r = 0.365, p = 0.027). High BMI was related to an increase in tongue volume. Modified Mallampati scores showed borderline significant positive correlations with absolute tongue volume (r = 0.251, p = 0.046) and standardized tongue volume (absolute tongue volume / intramandibular area; r = 0.266, p = 0.034). Between the normal-mild and moderate-severe groups, absolute tongue volumes were not different, although the standardized tongue volume in the moderate-severe group was significantly higher. CONCLUSION: Absolute tongue volume showed stronger associations with lowest O2 saturation during sleep than with the severity of AHI. We also found that high BMI was a relevant factor for an increase in absolute tongue volume and modified Mallampati grading was a useful physical examination to predict tongue size. PMID- 26280547 TI - Multivariate analysis of ball possessions effectiveness in elite futsal. AB - The aim of the present study was to identify the importance of ball possessions effectiveness in elite futsal according to space- and task-related indicators and situational variables. The sample was composed of 2327 ball possessions, corresponding to 9 close matches (1 goal of score difference) and selected from the playoff matches of the Spanish Futsal League (2012-2013). The binary logistic regression and classification tree (Exhaustive-Chi-squared Automatic Interaction Detection) multivariate models were used to identify the best predictor variables on the most successful ball possessions. Results from binomial logistic regression emphasised the relationships of ending in the goalkeeper's area and half-court defensive pressure with effectiveness. The individual defence, set play, and 0-3 passes used were found to be related to unsuccessful ball possessions. The classification tree results identified higher effectiveness during stopped balls or during set play that ended in zones 80, 60, 41, 20 and 10, and used more than 4 passes. Additionally, negative effects were observed in set plays that used less than 4 passes, individual defences and ended in zones 90, 70, 61, 40 and 30. The identified trends allow coaches to improve strategic plans that involve selecting the most appropriate offensive and defensive approaches when performing ball possessions in futsal. PMID- 26280548 TI - A High Burden Human Immunodeficiency Virus and Tuberculosis Resource Limited Setting, Gains from Including Xpert MTB/RIF in the Diagnostic Algorithm of Fluid Specimens Submitted for Exclusion of Lymphoma by Immunophenotypic Analysis. AB - This study investigated the benefit of incorporating Xpert MTB/RIF into the diagnostic algorithm of fluid specimens received for immunophenotypic analysis to exclude lymphoma. It was found that in a high burden HIV/TB setting, like South Africa, 130/229 (57%) of fluid specimens referred for immunophenotypic analysis to exclude lymphoma are not referred for concurrent MTBC liquid culture testing by the treating clinician. Of 99/229 (43%) specimens with corresponding culture results, Xpert sensitivity and specificity were 50% (CI:26-75%) and 99% (CI:91 100%) respectively. This demonstrates that incorporation of Xpert into the laboratory diagnostic algorithm in the immunophenotypic laboratory would improve patient work-up and care. PMID- 26280554 TI - A new silver nanochain SERS analytical platform to detect trace hexametaphosphate with a rhodamine S molecular probe. AB - Using AgNO3 as the precursor, stable silver nanochain (AgNC) sols, orange-red in color, were prepared using hydrazine hydrate. A strong surface plasmon resonance Rayleigh scattering (RRS) peak occurred at 420 nm plus two surface plasmon resonance (SPR) absorption peaks at 410 nm and 510 nm. Rhodamine S (RhS) cationic dye was absorbed on the as-prepared AgNC substrate to obtain a RhS-AgNC surface enhanced Raman scattering (SERS) nanoprobe that exhibited a strong SERS peak at 1506 cm(-1) and a strong RRS peak at 375 nm. Upon addition of the analyte sodium hexametaphosphate (HP), it reacted with RhS, which resulted in a decrease in the SERS and RRS peaks that was studied in detail. The decreased SERS and RRS intensities correlated linearly with HP concentration in the range of 0.0125-0.3 umol/L and 0.05-1.0 umol/L, with a detection limit of 6 nmol/L and 20 nmol/L HP respectively. Due to advantages of high sensitivity, good selectivity and simple operation, the RhS molecular probes were used to determine HP concentration in real samples. PMID- 26280555 TI - Minimization of Synthetic Polymer Ligands for Specific Recognition and Neutralization of a Toxic Peptide. AB - Synthetic polymer ligands (PLs) that recognize and neutralize specific biomacromolecules have attracted attention as stable substitutes for ligands such as antibodies and aptamers. PLs have been reported to strongly interact with target proteins and can be prepared by optimizing the combination and relative proportion of functional groups, by molecular imprinting polymerization, and/or by affinity purification. However, little has been reported about a strategy to prepare PLs capable of specifically recognizing a peptide from a group of targets with similar molecular weight and amino acid composition. In this study, we show that such PLs can be prepared by minimization of molecular weight and density of functional units. The resulting PLs recognize the target toxin exclusively and with 100-fold stronger affinity from a mixture of similar toxins. The target toxin is neutralized as a result. We believe that the minimization approach will become a valuable tool to prepare "plastic aptamers" with strong affinity for specific target peptides. PMID- 26280556 TI - Abnormal resting-state functional connectivity of the nucleus accumbens in multi year abstinent heroin addicts. AB - Functional neuroimaging studies suggest that abnormal brain functional connectivity may be the neural underpinning of addiction to illicit drugs and of relapse after successful cessation therapy. Aberrant brain networks have been demonstrated in addicted patients and in newly abstinent addicts. However, it is not known whether abnormal brain connectivity patterns persist after prolonged abstinence. In this cross-sectional study, whole-brain resting-state functional magnetic resonance images (8 min) were collected from 30 heroin-addicted individuals after a long period of abstinence (more than 3 years) and from 30 healthy controls. We first examined the group differences in the resting-state functional connectivity of the nucleus accumbens (NAc), a brain region implicated in relapse-related processes, including craving and reactivity to stress following acute and protracted withdrawal from heroin. We then examined the relation between the duration of abstinence and the altered NAc functional connectivity in the heroin group. We found that, compared with controls, heroin dependent participants exhibited significantly greater functional connectivity between the right ventromedial prefrontal cortex and the NAc and weaker functional connectivity between the NAc and the left putamen, left precuneus, and supplementary motor area. However, with longer abstinence time, the strength of NAc functional connectivity with the left putamen increased. These results indicate that dysfunction of the NAc functional network is still present in long term-abstinent heroin-dependent individuals. PMID- 26280557 TI - How the Plant Temperature Links to the Air Temperature in the Desert Plant Artemisia ordosica. AB - Plant temperature (Tp) is an important indicator of plant health. To determine the dynamics of plant temperature and self-cooling ability of the plant, we measured Tp in Artemisia ordosica in July, in the Mu Us Desert of Northwest China. Related factors were also monitored to investigate their effects on Tp, including environmental factors, such as air temperature (Ta), relative humidity, wind speed; and physiological factors, such as leaf water potential, sap flow, and water content. The results indicate that: 1) Tp generally changes in conjunction with Ta mainly, and varies with height and among the plant organs. Tp in the young branches is most constant, while it is the most sensitive in the leaves. 2) Correlations between Tp and environmental factors show that Tp is affected mainly by Ta. 3) The self-cooling ability of the plant was effective by midday, with Tp being lower than Ta. 4) Increasing sap flow and leaf water potential showed that transpiration formed part of the mechanism that supported self-cooling. Increased in water conductance and specific heat at midday may be additional factors that contribute to plant cooling ability. Therefore, our results confirmed plant self-cooling ability. The response to high temperatures is regulated by both transpiration speed and an increase in stem water conductance. This study provides quantitative data for plant management in terms of temperature control. Moreover, our findings will assist species selection with taking plant temperature as an index. PMID- 26280558 TI - Does Clinical Treatment with Phenylbutazone and Meloxicam in the Pre-ovulatory Period Influence the Ovulation Rate in Mares? AB - The presence of anovulatory haemorrhagic follicles during the oestrous cycle of mares causes financial impacts, slowing conception and increasing the number of services per pregnancy. Non-steroidal anti-inflammatory drugs (NSAIDs) such as meloxicam and phenylbutazone are used in the treatment of several disorders in mares, and these drugs can impair the formation of prostaglandins (PGs) and consequently interfere with reproductive activity. This study aimed to evaluate the effects of treatment with NSAIDs on the development of pre-ovulatory follicles in mares. In total, 11 mares were studied over three consecutive oestrous cycles, and gynaecological and ultrasound examinations were performed every 12 h. When 32-mm-diameter follicles were detected, 1 mg of deslorelin was administered to induce ovulation. The first cycle was used as a control, and the mares received only a dose of deslorelin. In the subsequent cycles, in addition to receiving the same dose of deslorelin, each mare was treated with NSAIDs. In the second cycle, 4.4 mg/kg of phenylbutazone was administered, and in the third cycle, 0.6 mg/kg of meloxicam was administered once a day until ovulation or the beginning of follicular haemorrhage. All of the mares ovulated between 36 and 48 h after the induction in the control cycle. In the meloxicam cycle, 10 mares (92%) did not ovulate, while in the phenylbutazone cycle, nine mares (83%) did not ovulate. In both treatments, intrafollicular hyperechoic spots indicative of haemorrhagic follicles were observed on ultrasound. Thus, our results suggested that treatment with meloxicam and phenylbutazone at therapeutic doses induced intrafollicular haemorrhage and luteinization of anovulatory follicles. PMID- 26280560 TI - Response to "Is the Reg3alpha (HIP/PAP) Protein Really an Obesogenic Factor?". PMID- 26280559 TI - Addition of radiotherapy to adjuvant chemotherapy is associated with improved overall survival in resected pancreatic adenocarcinoma: An analysis of the National Cancer Data Base. AB - BACKGROUND: The optimal treatment for resected pancreatic cancer is controversial because direct comparisons of adjuvant chemotherapy (CT) alone and chemotherapy and radiotherapy (CRT) are limited. This study assessed outcomes of CT versus CRT in a national cohort to provide a modern estimate of comparative effectiveness. METHODS: Patients with pT1-3N0-1M0 pancreatic adenocarcinoma after pancreatectomy were identified in the National Cancer Data Base. Overall survival (OS) was compared for CT and CRT groups with Cox regression and propensity score matching. Subset analyses by clinicopathologic characteristics were performed. RESULTS: This study identified 6165 patients treated with CT (n = 2334 or 38%) or CRT (n = 3831 or 62%). Most were classified as pT3 (72%), pN1 (67%), and status-post R0 resection (84%). For CRT patients, the median radiotherapy dose was 50.4 Gy. Compared with CT, CRT was associated with improved OS in a univariate analysis (median, 20.0 vs 22.3 months; at 5 years, 16.5% vs 19.6%; P < .001) and a multivariate analysis (hazard ratio [HR], 0.893; 95% confidence interval [CI], 0.837-0.953; P = .001). CRT remained associated with improved OS after propensity score matching (HR, 0.851; 95% CI, 0.793-0.913; P < .001). Subset analyses showed that CRT was associated with improved OS among patients with pT3 (HR, 0.892; 95% CI, 0.828-0.962; P = .003) or pN1 disease (HR, 0.856; 95% CI, 0.793-0.924; P < .001) and both R0 resection (HR, 0.901; 95% CI, 0.839-0.969; P = .005) and R1 resection (HR, 0.842; 95% CI, 0.722-0.983; P = .030). CONCLUSIONS: CRT was independently associated with improved OS after the resection of pancreatic adenocarcinoma in a large national cohort and particularly among patients with R1 resection and pN1 disease. Well-designed randomized comparisons of CRT and CT are urgently needed. PMID- 26280562 TI - Age- and Functional Status-Dependent Association Between Blood Pressure and Cognition: The Milan Geriatrics 75+ Cohort Study. AB - OBJECTIVES: To evaluate whether the relationship between blood pressure (BP) measures and cognitive function is different according to age and functional status in older outpatients. DESIGN: Cross-sectional. SETTING: Outpatient hospital-based Milan Geriatrics 75+ Cohort Study. PARTICIPANTS: Individuals aged 75 and older (N = 1,540). MEASUREMENTS: Blood pressure, Mini-Mental State Examination (MMSE), basic activities of daily living (ADLs), and instrumental activities of daily living (IADLs) were assessed. Associations between BP measures and MMSE score were first analyzed in the total population using linear regression models and were then further examined according to strata of age, ADLs, and IADLs. All analyses were adjusted for sociodemographic factors and presence of comorbidities. RESULTS: In the total population, higher systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP), and mean arterial pressure (MAP) were all associated with higher MMSE score (all P < .05). Each 10-mmHg higher SBP and DBP was associated with a 0.26- and 0.55-point higher MMSE score, respectively. The associations between MMSE score and SBP, DBP, and MAP differed materially according to strata of age and functioning and were most pronounced in those aged 85 and older, with ADL impairments, and with IADL impairments. CONCLUSION: Higher BP is associated with better cognitive function in the oldest old and in those with impaired functional status. PMID- 26280561 TI - Surface display of Aggregatibacter actinomycetemcomitans autotransporter Aae and dispersin B hybrid act as antibiofilm agents. AB - Among the various proteins expressed by the periodontopathogen Aggregatibacter actinomycetemcomitans, two proteins play important roles for survival in the oral cavity. The autotransporter Aae facilitates the attachment of the pathogen to oral epithelial cells, which act as a reservoir, while the biofilm-degrading glycoside hydrolase dispersin B facilitates the movement of daughter cells from the mature biofilm to a new site. The objective of this study was to use the potential of these two proteins to control biofilms. To this end, we generated a hybrid construct between the Aae C-terminal translocating domain and dispersin B, and mobilized it into Escherichia coli Rosetta (DE3) pLysS cells. Immunofluorescence analysis of the modified E. coli cells confirmed the presence of dispersin B on the surface. Further, the membrane localization of the displayed dispersin B was confirmed with Western blot analysis. The integrity of the E. coli cells displaying the dispersin B was confirmed through FACS analysis. The hydrolytic activity of the surface-displayed dispersin B was confirmed by using 4-methylumbelliferyl-beta-d-glucopyranoside as the substrate. The detachment ability of the dispersin B surface-displaying E. coli cells was shown using Staphylococcus epidermidis and Actinobacillus pleuropneumoniae biofilms in a microtiter assay. We concluded that the Aae beta-domain is sufficient to translocate foreign enzymes in the native folded form and that the method of Aae mediated translocation of surface displayed enzymes might be useful for control of biofilms. PMID- 26280564 TI - Binding affinities by alchemical perturbation using QM/MM with a large QM system and polarizable MM model. AB - The most general way to improve the accuracy of binding-affinity calculations for protein-ligand systems is to use quantum-mechanical (QM) methods together with rigorous alchemical-perturbation (AP) methods. We explore this approach by calculating the relative binding free energy of two synthetic disaccharides binding to galectin-3 at a reasonably high QM level (dispersion-corrected density functional theory with a triple-zeta basis set) and with a sufficiently large QM system to include all short-range interactions with the ligand (744-748 atoms). The rest of the protein is treated as a collection of atomic multipoles (up to quadrupoles) and polarizabilities. Several methods for evaluating the binding free energy from the 3600 QM calculations are investigated in terms of stability and accuracy. In particular, methods using QM calculations only at the endpoints of the transformation are compared with the recently proposed non-Boltzmann Bennett acceptance ratio (NBB) method that uses QM calculations at several stages of the transformation. Unfortunately, none of the rigorous approaches give sufficient statistical precision. However, a novel approximate method, involving the direct use of QM energies in the Bennett acceptance ratio method, gives similar results as NBB but with better precision, ~3 kJ/mol. The statistical error can be further reduced by performing a greater number of QM calculations. PMID- 26280565 TI - Developing and Pilot Testing the Readiness and Motivation Interview for Families in Pediatric Weight Management. AB - Clinical acumen is often used to assess families' motivation prior to initiating pediatric obesity management due to a lack of available tools. The purpose of this pilot study was to (i) develop and (ii) pilot test the "Readiness and Motivation Interview for Families" (RMI-Family) in pediatric weight management. We conducted 5 focus groups with parents (n = 15), youth with obesity (n = 11), and health care providers (n = 8) to explore perceptions of barriers to making healthy behaviour changes, which led to the creation of the RMI-Family as a semi structured interview. Five domains (treat foods, overeating, emotional eating, total physical activity, and screen time) emerged from the focus groups to inform the development of the RMI-Family, which was then pilot tested with a sample of youth with obesity and their parents (n = 11 dyads). Interviewers administered the RMI-Family to youth (age 12.8 +/- 1.7 years; body mass index [BMI] z-score: 2.71 +/- 0.43) and parents (age 47.1 +/- 3.7 years; BMI: 33.5 +/- 10.1 kg/m(2)). The RMI-Family was feasible to administer, easily understood by families, and may be a useful tool for assessing families' motivation. Research is underway to determine the psychometric properties and utility of the RMI-Family in predicting clinical outcomes in pediatric weight management. PMID- 26280566 TI - Environment learning using descriptions or navigation: The involvement of working memory in young and older adults. AB - This study examined age-related differences between young and older adults in the involvement of verbal and visuo-spatial components of working memory (WM) when paths are learned from verbal and visuo-spatial inputs. A sample of 60 young adults (20-30 years old) and 58 older adults (60-75 years old) learned two paths from the person's point of view, one displayed in the form of a video showing the path, the other presenting the path in a verbal description. During the learning phase, participants concurrently performed a verbal task (articulatory suppression, AS group), or a visuo-spatial task (spatial tapping, ST group), or no secondary task (control, C group). After learning each path, participants completed tasks that involved the following: (1) recalling the sequential order and the location of landmarks; and (2) judging spatial sentences as true or false (verification test). The results showed that young adults outperformed older adults in all recall tasks. In both age groups performance in all types of task was worse in the AS and ST groups than in the C group, irrespective of the type of input. Overall, these findings suggest that verbal and visuo-spatial components of WM underpin the processing of environmental information in both young and older adults. The results are discussed in terms of age-related differences and according to the spatial cognition framework. PMID- 26280567 TI - Validation of a combined autosomal/Y-chromosomal STR approach for analyzing typical biological stains in sexual-assault cases. AB - DNA testing is an established part of the investigation and prosecution of sexual assault. The primary purpose of DNA evidence is to identify a suspect and/or to demonstrate sexual contact. However, due to highly uneven proportions of female and male DNA in typical stains, routine autosomal analysis often fails to detect the DNA of the assailant. To evaluate the forensic efficiency of the combined application of autosomal and Y-chromosomal short tandem repeat (STR) markers, we present a large retrospective casework study of probative evidence collected in sexual-assault cases. We investigated up to 39 STR markers by testing combinations of the 16-locus NGMSElect kit with both the 23-locus PowerPlex Y23 and the 17-locus Yfiler kit. Using this dual approach we analyzed DNA extracts from 2077 biological stains collected in 287 cases over 30 months. To assess the outcome of the combined approach in comparison to stand-alone autosomal analysis we evaluated informative DNA profiles. Our investigation revealed that Y-STR analysis added up to 21% additional, highly informative (complete, single-source) profiles to the set of reportable autosomal STR profiles for typical stains collected in sexual-assault cases. Detection of multiple male contributors was approximately three times more likely with Y-chromosomal profiling than with autosomal STR profiling. In summary, 1/10 cases would have remained inconclusive (and could have been dismissed) if Y-STR analysis had been omitted from DNA profiling in sexual-assault cases. PMID- 26280568 TI - Effect of multiple allelic drop-outs in forensic RMNE calculations. AB - Technological advances such as massively parallel sequencing enable increasing amounts of genetic information to be obtained from increasingly challenging samples. Certainly on low template, degraded and multi-contributor samples, drop outs will increase in number for many profiles simply by analyzing more loci, making it difficult to probabilistically assess how many drop-outs have occurred and at which loci they might have occurred. Previously we developed a Random Man Not Excluded (RMNE) method that can take into account allelic drop-out while avoiding detailed estimations of the probability that drop-outs have occurred, nor making assumptions about at which loci these drop-outs might have occurred. The number of alleles that have dropped out, does not need to be exactly known. Here we report a generic Python algorithm to calculate the RMNE probabilities for any given number of loci. The number of allowed drop-outs can be set between 0 and twice the number of analyzed loci. The source code has been made available on https://github.com/fvnieuwe/rmne. An online web-based RMNE calculation tool has been made available on http://forensic.ugent.be/rmne. The tool can calculate these RMNE probabilities from a custom list of probabilities of the observed and non-observed alleles from any given number of loci. Using this tool, we explored the effect of allowing allelic drop-outs on the evidential value of random forensic profiles with a varying number of loci. Our results give insight into how the number of allowed drop-outs affects the evidential value of a profile and how drop-out can be managed in the RMNE approach. PMID- 26280570 TI - Generating the Nighttime Light of the Human Settlements by Identifying Periodic Components from DMSP/OLS Satellite Imagery. AB - Nighttime lights of the human settlements (hereafter, "stable lights") are seen as a valuable proxy of social economic activity and greenhouse gas emissions at the subnational level. In this study, we propose an improved method to generate the stable lights from Defense Meteorological Satellite Program/Operational Linescan System (DMSP/OLS) daily nighttime light data for 1999. The study area includes Japan, China, India, and other 10 countries in East Asia. A noise reduction filter (NRF) was employed to generate a stable light from DMSP/OLS time series daily nighttime light data. It was found that noise from amplitude of the 1-year periodic component is included in the stable light. To remove the amplitude of the 1-year periodic component noise included in the stable light, the NRF method was improved to extract the periodic component. Then, new stable light was generated by removing the amplitude of the 1-year periodic component using the improved NRF method. The resulting stable light was evaluated by comparing it with the conventional nighttime stable light provided by the National Oceanic and Atmosphere Administration/National Geophysical Data Center (NOAA/NGDC). It is indicated that DNs of the NOAA stable light image are lower than those of the new stable light image. This might be attributable to the influence of attenuation effects from thin warm water clouds. However, due to overglow effect of the thin cloud, light area in new stable light is larger than NOAA stable light. Furthermore, the cumulative digital numbers (CDNs) and number of light area pixels (NLAP) of the generated stable light and NOAA/NGDC stable light were applied to estimate socioeconomic variables of population, electric power consumption, gross domestic product, and CO2 emissions from fossil fuel consumption. It is shown that the correlations of the population and CO2FF with new stable light data are higher than those in NOAA stable light data; correlations of the EPC and GDP with NOAA stable light data are higher those in the new stable light data. PMID- 26280569 TI - Posttraumatic Headache: Clinical Characterization and Management. AB - Headache is the most common symptom after traumatic brain injury (TBI). TBI has become a global health concern with an estimated 2.5 million reported TBIs per year in the USA alone. Recent longitudinal studies of posttraumatic headache (PTH) show a high cumulative incidence of 71 % after moderate or severe TBI and an even higher cumulative incidence of 91 % after mild TBI (mTBI) at 1 year after injury. Prevalence remains high at over 44 % throughout the year after moderate or severe TBI and over 54 % after mTBI. A prior history of headache is associated with a higher risk for PTH, whereas older age appears to be protective. Gender does not appear to be a risk factor for PTH. Most PTH has clinical diagnostic criteria meeting that of migraine or probable migraine when primary headache disorder classification criteria are used, followed by tension-type headache. There are no evidence-based treatment guidelines for PTH management; however, expert opinion has suggested treating the PTH using primary headache disorder treatment recommendations according to its type. PMID- 26280571 TI - Ag-Decorated ATaO3 (A = K, Na) Nanocube Plasmonic Photocatalysts with Enhanced Photocatalytic Water-Splitting Properties. AB - Tantalate semiconductor nanocrystals have been at the forefront of the photocatalytic conversion of solar energy to supply hydrogen owing to their favorable and tunable optical and electronic properties as well as advances in their synthesis. However, a narrow band gap is required for response to improve the efficiency of the photocatalysts. Here we propose an efficient enhancement of the H2 generation under simulated sunlight and visible light irradiation by a dispersion of Ag-decorated KTaO3 and NaTaO3 nanocubes. X-ray diffraction and UV vis diffuse reflectance spectra are used to characterize the products. Transmission electron microscope (TEM) and high-resolution high-angle annular dark-field scanning TEM (HAADF-STEM) images show that the Ag nanoparticles (NPs) are uniformly loaded on the surfaces of KTaO3 and NaTaO3. The photocatalytic water-splitting results over Ag-decorated KTaO3 and NaTaO3 show that the rate for H2 evolution from aqueous CH3OH solutions is up to 185.60 and 3.54 MUmol/h.g under simulated sunlight and the rate for H2 evolution is more than 2 times than that of pure NaTaO3 and KTaO3 materials. However, under purely visible light illumination the highest H2 evolution of 25.94 and 0.83 MUmol/h.g is observed in the case of Ag-decorated KTaO3 and NaTaO3 nanocubes. To the best of our knowledge, this is the first time that the photocatalytic water-splitting activity of the prepared Ag-decorated KTaO3 and NaTaO3 nanocubes has been reported. PMID- 26280572 TI - Tuning the Electronic Structure of Graphene by Molecular Dopants: Impact of the Substrate. AB - A combination of ultraviolet and X-ray photoelectron spectroscopy, X-ray absorption spectroscopy, and first principle calculations was used to study the electronic structure at the interface between the strong molecular acceptor 1,3,4,5,7,8-hexafluorotetracyano-naphthoquinodimethane (F6TCNNQ) and a graphene layer supported on either a quartz or a copper substrate. We find evidence for fundamentally different charge redistribution mechanisms in the two ternary systems, as a consequence of the insulating versus metallic character of the substrates. While electron transfer occurs exclusively from graphene to F6TCNNQ on the quartz support (p-doping of graphene), the Cu substrate electron reservoir induces an additional electron density flow to graphene decorated with the acceptor monolayer. Remarkably, graphene on Cu is n-doped and remains n-doped upon F6TCNNQ deposition. On both substrates, the work function of graphene increases substantially with a F6TCNNQ monolayer atop, the effect being more pronounced (~1.3 eV) on Cu compared to quartz (~1.0 eV) because of the larger electrostatic potential drop associated with the long-distance graphene-mediated Cu-F6TCNNQ electron transfer. We thus provide a means to realize high work function surfaces for both p- and n-type doped graphene. PMID- 26280573 TI - Experimental and Theoretical Investigations of Infrared Multiple Photon Dissociation Spectra of Glutamine Complexes with Zn(2+) and Cd(2.). AB - Complexes of glutamine (Gln) cationized with Zn(2+) and Cd(2+) were examined by infrared multiple photon dissociation (IRMPD) action spectroscopy using light generated from a free-electron laser. Electrospray ionization yielded complexes of deprotonated Gln with Zn(2+), [Zn(Gln-H)](+), and intact Gln with CdCl(+), CdCl(+)(Gln). For each complex, the spectra obtained were compared with those for low-energy conformers found using quantum chemical calculations to identify the structures present experimentally. Calculations were performed at the B3LYP/6 311+G(d,p) level for [Zn(Gln-H)](+) and at the B3LYP/def2-TZVP level with an SDD effective core potential on cadmium for CdCl(+)(Gln). The main binding motif observed for the Cd(2+) complex was a charge-solvated, tridentate [N,CO,COsc] structure in which the metal binds to the backbone amino group and the carbonyl oxygens of the carboxylic acid and side-chain amide groups. The Zn(2+) system similarly preferred a [N,CO(-),COsc] binding motif, where binding was observed at the carboxylate site along with the backbone amino and side-chain carbonyl groups. In both cases, the theoretically determined lowest-energy conformers explain the experimental [Zn(Gln-H)](+) and CdCl(+)(Gln) spectra well. PMID- 26280574 TI - Mucosally transplanted mesenchymal stem cells stimulate intestinal healing by promoting angiogenesis. AB - Mesenchymal stem cell (MSC) therapy is an emerging field of regenerative medicine; however, it is often unclear how these cells mediate repair. Here, we investigated the use of MSCs in the treatment of intestinal disease and modeled abnormal repair by creating focal wounds in the colonic mucosa of prostaglandin deficient mice. These wounds developed into ulcers that infiltrated the outer intestinal wall. We determined that penetrating ulcer formation in this model resulted from increased hypoxia and smooth muscle wall necrosis. Prostaglandin I2 (PGI2) stimulated VEGF-dependent angiogenesis to prevent penetrating ulcers. Treatment of mucosally injured WT mice with a VEGFR inhibitor resulted in the development of penetrating ulcers, further demonstrating that VEGF is critical for mucosal repair. We next used this model to address the role of transplanted colonic MSCs (cMSCs) in intestinal repair. Compared with intravenously injected cMSCs, mucosally injected cMSCs more effectively prevented the development of penetrating ulcers, as they were more efficiently recruited to colonic wounds. Importantly, mucosally injected cMSCs stimulated angiogenesis in a VEGF-dependent manner. Together, our results reveal that penetrating ulcer formation results from a reduction of local angiogenesis and targeted injection of MSCs can optimize transplantation therapy. Moreover, local MSC injection has potential for treating diseases with features of abnormal angiogenesis and repair. PMID- 26280575 TI - SLFN14 mutations underlie thrombocytopenia with excessive bleeding and platelet secretion defects. AB - Inherited thrombocytopenias are a group of disorders that are characterized by a low platelet count and are sometimes associated with excessive bleeding that ranges from mild to severe. We evaluated 36 unrelated patients and 17 family members displaying thrombocytopenia that were recruited to the UK Genotyping and Phenotyping of Platelets (GAPP) study. All patients had a history of excessive bleeding of unknown etiology. We performed platelet phenotyping and whole-exome sequencing (WES) on all patients and identified mutations in schlafen 14 (SLFN14) in 12 patients from 3 unrelated families. Patients harboring SLFN14 mutations displayed an analogous phenotype that consisted of moderate thrombocytopenia, enlarged platelets, decreased ATP secretion, and a dominant inheritance pattern. Three heterozygous missense mutations were identified in affected family members and predicted to encode substitutions (K218E, K219N, and V220D) within an ATPase AAA-4, GTP/ATP-binding region of SLFN14. Endogenous SLFN14 expression was reduced in platelets from all patients, and mutant SLFN14 expression was markedly decreased compared with that of WT SLFN14 when overexpressed in transfected cells. Electron microscopy revealed a reduced number of dense granules in affected patients platelets, correlating with a decreased ATP secretion observed in lumiaggregometry studies. These results identify SLFN14 mutations as cause for an inherited thrombocytopenia with excessive bleeding, outlining a fundamental role for SLFN14 in platelet formation and function. PMID- 26280578 TI - All the Good People. PMID- 26280577 TI - Sex ratio following preconception low-dose aspirin in women with prior pregnancy loss. AB - BACKGROUND: Several lines of evidence suggest that male embryos may have greater vulnerability than female embryos to disordered inflammation; therefore, antiinflammatory drugs, such as low-dose aspirin (LDA), may alter the sex ratio. Here, we assessed the effect of LDA on male live birth and male offspring, incorporating pregnancy losses (n = 56) via genetic assessment, as part of a parallel-design, block-randomized, placebo-controlled trial of preconception LDA. METHODS: Participants (615 treated with LDA, 613 treated with placebo) ranged in age from 18 to 40 years of age, with 1 to 2 prior pregnancy losses. We estimated the intention-to-treat (ITT) risk ratio (RR) and 95% CI and assessed interaction with baseline high-sensitivity C-reactive protein (hsCRP) serum concentration - a marker of systemic inflammation. RESULTS: Among the 1,078 women who completed follow-up (535 treated with LDA, 543 treated with placebo), the male live birth ITT RR equaled 1.31 (95% CI: 1.07-1.59). With increasing tertile of hsCRP, the proportion of males at birth decreased in the placebo group, and the effect of LDA on male live birth increased (first tertile: 48% male in LDA vs. 52% in placebo, ITT RR = 0.97, 95% CI: 0.70-1.35; second tertile: 57% male in LDA vs. 43% in placebo, ITT RR = 1.36, 95% CI: 0.98-1.90; third tertile: 53% male in LDA vs. 35% in placebo, ITT RR = 1.70, 95% CI: 1.13-2.57; P interaction = 0.03). Analysis of pregnancy with male offspring yielded similar results. CONCLUSION: Initiation of LDA prior to conception restored numbers of male live births and pregnancy with male offspring among women with 1 to 2 prior pregnancy losses. Moreover, our data suggest that LDA modulates inflammation that would otherwise reduce the conception or survival of male embryos. TRIAL REGISTRATION: ClinicalTrials.gov NCT00467363. FUNDING: Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. PMID- 26280576 TI - HDAC inhibitor-dependent transcriptome and memory reinstatement in cognitive decline models. AB - Aging and increased amyloid burden are major risk factors for cognitive diseases such as Alzheimer's disease (AD). Effective therapies for these diseases are lacking. Here, we evaluated mouse models of age-associated memory impairment and amyloid deposition to study transcriptome and cell type-specific epigenome plasticity in the brain and peripheral organs. We determined that aging and amyloid pathology are associated with inflammation and impaired synaptic function in the hippocampal CA1 region as the result of epigenetic-dependent alterations in gene expression. In both amyloid and aging models, inflammation was associated with increased gene expression linked to a subset of transcription factors, while plasticity gene deregulation was differentially mediated. Amyloid pathology impaired histone acetylation and decreased expression of plasticity genes, while aging altered H4K12 acetylation-linked differential splicing at the intron-exon junction in neurons, but not nonneuronal cells. Furthermore, oral administration of the clinically approved histone deacetylase inhibitor vorinostat not only restored spatial memory, but also exerted antiinflammatory action and reinstated epigenetic balance and transcriptional homeostasis at the level of gene expression and exon usage. This study provides a systems-level investigation of transcriptome plasticity in the hippocampal CA1 region in aging and AD models and suggests that histone deacetylase inhibitors should be further explored as a cost effective therapeutic strategy against age-associated cognitive decline. PMID- 26280579 TI - Introduction of Francis S. Collins. PMID- 26280582 TI - Placental Sonolucencies in the First Trimester: Incidence and Clinical Significance. AB - OBJECTIVES: The aims of this study were to determine the incidence of placental sonolucencies on first-trimester screening sonograms in a general obstetric population and assess whether these findings are associated with adverse obstetric outcomes. METHODS: A retrospective cohort analysis of 201 pregnant patients screened at a high-risk prenatal diagnostic center was conducted with first-trimester cine clips reviewed by 2 radiologists. Placental sonolucencies were defined as intraplacental anechoic or heterogeneous areas 0.7 cm or greater. Obstetric and neonatal outcomes were collected by chart review. RESULTS: Placental sonolucencies 0.7 cm or greater were seen in 45 (22.4%) of first trimester ultrasound examinations. The ultrasonographic presence of a placenta previa, marginal sinus, and subchorionic hemorrhage was not more common in those with placental sonolucencies 0.7 cm or greater (P > 0.05). Sonolucencies were not associated with prior cesarean deliveries (P > 0.05). Both the groups with and without sonolucencies 0.7 cm or greater had similar rates of antepartum hemorrhage, preeclampsia, preterm delivery, cesarean delivery, postpartum hemorrhage, and delivery of small-for-gestational-age infants. One placenta accreta and no fetal demises occurred in the study population. CONCLUSIONS: Placental sonolucencies detected on first-trimester screening sonograms in the general obstetric population are not predictive of poor obstetric outcomes. PMID- 26280581 TI - Analysis of conditional heterozygous STXBP1 mutations in human neurons. AB - Heterozygous mutations in the syntaxin-binding protein 1 (STXBP1) gene, which encodes Munc18-1, a core component of the presynaptic membrane-fusion machinery, cause infantile early epileptic encephalopathy (Ohtahara syndrome), but it is unclear how a partial loss of Munc18-1 produces this severe clinical presentation. Here, we generated human ES cells designed to conditionally express heterozygous and homozygous STXBP1 loss-of-function mutations and studied isogenic WT and STXBP1-mutant human neurons derived from these conditionally mutant ES cells. We demonstrated that heterozygous STXBP1 mutations lower the levels of Munc18-1 protein and its binding partner, the t-SNARE-protein Syntaxin 1, by approximately 30% and decrease spontaneous and evoked neurotransmitter release by nearly 50%. Thus, our results confirm that using engineered human embryonic stem (ES) cells is a viable approach to studying disease-associated mutations in human neurons on a controlled genetic background, demonstrate that partial STXBP1 loss of function robustly impairs neurotransmitter release in human neurons, and suggest that heterozygous STXBP1 mutations cause early epileptic encephalopathy specifically through a presynaptic impairment. PMID- 26280580 TI - RAP1-mediated MEK/ERK pathway defects in Kabuki syndrome. AB - The genetic disorder Kabuki syndrome (KS) is characterized by developmental delay and congenital anomalies. Dominant mutations in the chromatin regulators lysine (K)-specific methyltransferase 2D (KMT2D) (also known as MLL2) and lysine (K) specific demethylase 6A (KDM6A) underlie the majority of cases. Although the functions of these chromatin-modifying proteins have been studied extensively, the physiological systems regulated by them are largely unknown. Using whole exome sequencing, we identified a mutation in RAP1A that was converted to homozygosity as the result of uniparental isodisomy (UPD) in a patient with KS and a de novo, dominant mutation in RAP1B in a second individual with a KS-like phenotype. We elucidated a genetic and functional interaction between the respective KS-associated genes and their products in zebrafish models and patient cell lines. Specifically, we determined that dysfunction of known KS genes and the genes identified in this study results in aberrant MEK/ERK signaling as well as disruption of F-actin polymerization and cell intercalation. Moreover, these phenotypes could be rescued in zebrafish models by rebalancing MEK/ERK signaling via administration of small molecule inhibitors of MEK. Taken together, our studies suggest that the KS pathophysiology overlaps with the RASopathies and provide a potential direction for treatment design. PMID- 26280583 TI - Application of Thyroid Imaging Reporting and Data System in the Ultrasound Assessment of Thyroid Nodules According to Physician Experience. AB - OBJECTIVE: The aim of this study was to investigate and compare the diagnostic performances of the Thyroid Imaging Reporting and Data System (TIRADS) in differentiating benign and malignant thyroid nodules according to the level of physician experience. MATERIALS AND METHODS: From March to October 2013, 1102 patients with 1128 thyroid nodules who underwent initial ultrasound-guided fine needle aspiration were included in this study. Thyroid nodules were categorized according to TIRADS. Diagnostic performances of ultrasound were compared according to performer experience using the chi test or Fisher exact test. RESULTS: Of 1128 thyroid nodules, 281 were malignant, and 847 were benign. The risk of malignancy of each TIRADS category by the experienced and less experienced physicians were as follows: category 3 (0.9% vs 0%), category 4a (3.5% vs 1.3%), category 4b (7.3% vs 12.1%), category 4c (67.5% vs 44.9%), and category 5 (97.7% vs 76.5%). Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 99.1%, 35.9%, 52.5%, 35.5%, and 99.1%, respectively, for experienced physicians and 100%, 20.9%, 37.6%, 35.2%, and 100%, respectively, for less experienced physicians. Specificity, accuracy, and positive predictive value were statistically higher for experienced physicians than those for less experienced physicians (P < 0.001, 0.001, and 0.004). There was a significant difference in areas under the curve between the 2 groups (P < 0.001). CONCLUSIONS: In conclusion, the diagnostic performance of the stratification of malignancy risk according to TIRADS categories was comparable between the experienced and less experienced physician groups. The application of TIRADS is reproducible, and it was easy to predict the probability of thyroid malignancy in both the experienced and less experienced physician groups. PMID- 26280584 TI - Comparison of U(VI) adsorption onto nanoscale zero-valent iron and red soil in the presence of U(VI)-CO3/Ca-U(VI)-CO3 complexes. AB - The influence of U(VI)-CO3 and Ca-U(VI)-CO3 complexes on U(VI) adsorption onto red soil and nanoscale zero-valent iron (NZVI) was investigated using batch adsorption and fixed-bed column experiments to simulate the feasibility of NZVI as the reactive medium in permeable- reactive barriers (PRB) for in situ remediation of uranium-contaminated red soils. The adsorption capacity (qe) and distribution constant (Kd) of NZVI and red soil decreased with increasing pH, dissolved carbonate and calcium concentrations, but the qe and Kd values of NZVI were 5-10 times higher than those of red soil. The breakthrough pore volume (PV) values increased with the decrease of pH, dissolved carbonate and calcium concentration; however, the breakthrough PV values of the PRB column filled with 5% NZVI were 2.0-3.5 times higher than the 100% red soil column. The U(VI)-CO3 complexes adsorbed onto the surface of red soil/NZVI (=SOH) to form SO-UO2CO3(-) or SO-UO2 (CO3)2(3-). XPS and XRD analysis further confirmed the reduction of U(VI) to U(IV) and the formation of FeOOH on NZVI surfaces. The findings of this study are significant to the remediation of uranium-contaminated red soils and the consideration of practical U(VI) species in the natural environment. PMID- 26280586 TI - Role of Postoperative Radiotherapy in Nonlocalized Thymoma: Propensity-Matched Analysis of Surveillance, Epidemiology, and End Results Database. AB - INTRODUCTION: Because of a lack of randomized trials, the role of postoperative radiotherapy (PORT) in thymomas has not been established. This study evaluated the prognostic impact of the adjuvant treatment in surgically resected nonlocalized thymomas. METHODS: Patients diagnosed between 2000 and 2010 were identified from the Surveillance, Epidemiology, and End Results database (1973 2011 registry). Cases with localized or organ-confined tumors were not included. Propensity-matched analysis was conducted considering baseline characteristics. RESULTS: A total of 529 patients were identified. The median age was 57 years (range, 18-86), and 345 (65%) patients received PORT. Before and after propensity score matching, overall survival (OS; p = 0.018 and 0.008, respectively) and disease-specific survival (DSS; p = 0.007 and 0.008, respectively) were better in the PORT group. In multivariate analyses of the matched population, no receipt of PORT induced poorer OS (hazard ratio [HR], 1.98; 95% confidence interval [CI], 1.27-3.09) and DSS (HR, 2.64; 95% CI, 1.32-5.29). Primary tumor extensions of adjacent organs or structures and further contiguous extensions also resulted in worse outcomes (p < 0.001 and equal to 0.039 for OS; p = 0.006 and 0.009 for DSS, respectively). In the subgroup analyses, PORT was associated with favorable OS in stages III and IV (p = 0.049 and 0.012, respectively) and DSS in stage III (p = 0.005). CONCLUSION: Regarding the independent prognostic significance of PORT, this population-based analysis demonstrates the survival benefits of PORT in relation to nonlocalized thymomas. We recommend consideration of PORT in the poor prognostic subset of stages III to IV in the contemporary era. PMID- 26280585 TI - The Antinociceptive and Antiinflammatory Properties of 3-furan-2-yl-N-p-tolyl acrylamide, a Positive Allosteric Modulator of alpha7 Nicotinic Acetylcholine Receptors in Mice. AB - BACKGROUND: Positive allosteric modulators (PAMs) facilitate endogenous neurotransmission and/or enhance the efficacy of agonists without directly acting on the orthosteric binding sites. In this regard, selective alpha7 nicotinic acetylcholine receptor type II PAMs display antinociceptive activity in rodent chronic inflammatory and neuropathic pain models. This study investigates whether 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2), a new putative alpha7-selective type II PAM, attenuates experimental inflammatory and neuropathic pains in mice. METHODS: We tested the activity of PAM-2 after intraperitoneal administration in 3 pain assays: the carrageenan-induced inflammatory pain, the complete Freund adjuvant-induced inflammatory pain, and the chronic constriction injury-induced neuropathic pain in mice. We also tested whether PAM-2 enhanced the effects of the selective alpha7 agonist choline in the mouse carrageenan test given intrathecally. Because the experience of pain has both sensory and affective dimensions, we also evaluated the effects of PAM-2 on acetic acid-induced aversion by using the conditioned place aversion test. RESULTS: We observed that systemic administration of PAM-2 significantly reversed mechanical allodynia and thermal hyperalgesia in inflammatory and neuropathic pain models in a dose- and time-dependent manner without motor impairment. In addition, by attenuating the paw edema in inflammatory models, PAM-2 showed antiinflammatory properties. The antinociceptive effect of PAM-2 was inhibited by the selective competitive antagonist methyllycaconitine, indicating that the effect is mediated by alpha7 nicotinic acetylcholine receptors. Furthermore, PAM-2 enhanced the antiallodynic and antiinflammatory effects of choline, a selective alpha7 agonist, in the mouse carrageenan test. PAM-2 was also effective in reducing acetic acid-induced aversion in the conditioned place aversion assay. CONCLUSIONS: These findings suggest that the administration of PAM-2, a new alpha7-selective type II PAM, reduces the neuropathic and inflammatory pain sensory and affective behaviors in the mouse. Thus, this drug may have therapeutic applications in the treatment and management of chronic pain. PMID- 26280587 TI - Community Health Workers Promoting Physical Activity: Targeting Multiple Levels of the Social Ecological Model. AB - The effectiveness of community health workers (CHWs) as health educators and health promoters among Latino populations is widely recognized. The Affordable Care Act created important opportunities to increase the role of CHWs in preventive health. This article describes the implementation of CHW-led, culturally specific, faith-based program to increase physical activity among churchgoing Latinas. This study augments previous research by describing the recruitment, selection, training, and evaluation of CHWs for a physical activity intervention targeting multiple levels of the Social Ecological Model. PMID- 26280588 TI - [Delayed indications for additive ventral treatment of thoracolumbar burst fractures : What correction loss is to be expected]. AB - INTRODUCTION: There is a general consensus that unstable vertebral body fractures of the thoracolumbar junction with a B type fracture or a high load shear index need to be surgically stabilized, primarily by a dorsal approach. The authors believe that there are indications for an additional ventral spondylodesis in cases of reduction loss or a relevant intervertebral disc lesion in magnetic resonance imaging (MRI) 6 weeks after dorsal stabilization. However, in cases of unstable vertebral fractures it remains unclear if a delayed anterior spondylodesis will lead to unacceptable loss of initial reduction. MATERIAL AND METHODS: A total of 59 patients were included in this study during 2013 and 2014. All patients suffered from a traumatic vertebral fracture of the thoracolumbar junction and were initially treated with a dorsal short segment stabilization. All vertebral body fractures had a load shear index of at least 5 or were B type fractures. An x-ray control was carried out after 2 and 6 weeks and MRI was additionally performed after 6 weeks. An additional ventral spondylodesis was recommended in patients showing a reduction loss of at least 5 degrees and in patients with relevant intervertebral disc lesions. The extent of the reduction loss was analyzed. Other parameters of interest were the fracture level, fracture classification, patient age and surgical technique (e.g. implant, index screw, laminectomy and cement augmentation). RESULTS: The patient collective consisted of 23 women and 36 men (average age 51 years +/- 17 years). The mean reduction loss was 5.1 degrees (+/- 5.2 degrees ) after a mean follow-up of 60 days (+/- 56 days). The reduction loss was significantly higher when polyaxial implants were used compared to monoaxial dorsal fixators (10.8 degrees versus 4.0 degrees , p < 0.001). There was a significantly higher reduction loss in those patients who received a laminectomy (11.3 degrees versus 4.3 degrees , p = 0.01) but there were no significant differences if an index screw was used (4.5 degrees versus 5.3 degrees ). Additionally, there was a significantly lower reduction in the subgroup of patients 60 years or older who were stabilized using cement augmented screws (3.9 degrees versus 11.3 degrees , p = 0.02). The mean reduction loss was 2.8 degrees (+/- 2.5 degrees ) in patients treated with a monoaxial implant, cement-augmented if 60 years or older and without laminectomy (n = 39). There was no significant correlation between reduction loss and the other parameters of interest, such as fracture morphology with classification according to the working group on questions of osteosynthesis (AO) and McCormack or fracture level. CONCLUSION: Delayed indications for an additional ventral spondylodesis in patients with unstable thoracolumbar vertebral fractures and initial dorsal stabilization will cause no relevant reduction loss if monoaxial implants are used and laminectomy can be avoided. Additionally, cement augmentation of the pedicle screws seems to be beneficial in patients 60 years of age or older. PMID- 26280589 TI - Contingency management for cigarette smokers with depressive symptoms. AB - Despite depressive symptoms being very common among smokers from the general population, few studies have examined the effects of depressive symptoms on smoking treatment outcomes, and even less research has been carried out in the context of contingency management (CM). The authors conducted a secondary analysis to assess the interrelation between treatment condition, depressive symptoms and treatment outcomes among treatment-seeking smokers. The sample was made up of 147 treatment-seeking smokers who were randomly allocated 2 treatment conditions: cognitive behavioral treatment (CBT; n = 74), or CBT + CM (n = 73). CBT was applied in 1-hr group-based sessions over 6 weeks. The CM protocol was voucher-based with maximum earnings of ?300 (US$339). Depressive symptoms were assessed using the Beck Depression Inventory-II. Smoking abstinence was verified though cotinine and carbon monoxide. Several analyses were conducted to explore the effect of treatment condition and baseline depressive symptoms on treatment outcomes, as well as the effect of treatment condition and smoking status on depressive symptoms. The CBT + CM condition was more effective than CBT, independent of depressive symptoms. The presence of depressive symptoms decreased the number of days of continuous smoking abstinence. Participants with a greater number of days of continuous smoking abstinence had fewer depressive symptoms than those with fewer days of continuous smoking abstinence. Findings suggest that health care providers should consider encouraging their patients with depressive symptoms to seek smoking cessation services that include both smoking cessation protocols and behavioral activation for mood management, thus maximizing both smoking and depressive outcomes. PMID- 26280590 TI - Experimental study on the effects of anxiety sensitivity and somatosensory amplification on the response to the 35% CO2 challenge in abstinent smokers. AB - The relationship between nicotine abstinence and panic onset is still not well understood and the role of catastrophic misinterpretation, as possible moderator or mediator of this relationship, is unknown. We tested whether nicotine abstinence influences the response to a CO2 panic challenge and whether catastrophic misinterpretation (measured via the Anxiety Sensitivity [ASI] and the SomatoSensory Amplification Scale [SSAS]) exerts a moderating or mediating effect on the relationship between nicotine abstinence and panic. Eighty regular smokers underwent a 35% CO2 challenge after the transdermal administration of nicotine or placebo. Physiological and psychological variables were measured at baseline, directly before and after the challenge. Fear reactivity to the challenge was similar in both conditions. ASI (post-Test Visual Analogous Scale of Fear: DeltaR2 = 0.043, p < .05) and SSAS (post-Test Visual Analogous Scale of Anxiety: DeltaR2 = 0.036, p < .05; post-Test Panic Symptom List: DeltaR2 = 0.035, p < .05) influenced anxiety as response to the challenge. We found no support for the moderational and the mediational hypotheses. The findings regarding fear reactivity when group status is considered partly confirm the literature. The positive findings observed for ASI and SSAS as factors influencing the response to the challenge, together with the lack of evidence for a moderational and a mediational hypothesis, confirm that anxiety sensitivity and somatosensory amplification are independent constructs and suggest that they directly influence the response to the challenge. PMID- 26280591 TI - A modified exponential behavioral economic demand model to better describe consumption data. AB - Behavioral economic demand analyses that quantify the relationship between the consumption of a commodity and its price have proven useful in studying the reinforcing efficacy of many commodities, including drugs of abuse. An exponential equation proposed by Hursh and Silberberg (2008) has proven useful in quantifying the dissociable components of demand intensity and demand elasticity, but is limited as an analysis technique by the inability to correctly analyze consumption values of zero. We examined an exponentiated version of this equation that retains all the beneficial features of the original Hursh and Silberberg equation, but can accommodate consumption values of zero and improves its fit to the data. In Experiment 1, we compared the modified equation with the unmodified equation under different treatments of zero values in cigarette consumption data collected online from 272 participants. We found that the unmodified equation produces different results depending on how zeros are treated, while the exponentiated version incorporates zeros into the analysis, accounts for more variance, and is better able to estimate actual unconstrained consumption as reported by participants. In Experiment 2, we simulated 1,000 datasets with demand parameters known a priori and compared the equation fits. Results indicated that the exponentiated equation was better able to replicate the true values from which the test data were simulated. We conclude that an exponentiated version of the Hursh and Silberberg equation provides better fits to the data, is able to fit all consumption values including zero, and more accurately produces true parameter values. PMID- 26280592 TI - A feasibility study of home-based contingency management with adolescent smokers of rural Appalachia. AB - Cigarette smoking among adolescents remains a significant public health concern. This problem is compounded in regions such as rural Appalachia where rates of smoking are consistently higher than national averages and access to treatments is limited. The current research evaluated a home-based contingency management program completed over the Internet with adolescent smokers recruited from rural Appalachia. Participants (N = 62) submitted 3 video recordings per day showing their breath carbon monoxide (CO) levels using a handheld CO monitor. Participants were assigned to either an active treatment condition (AT; n = 31) in which reductions in breath CO were reinforced or a control treatment condition (CT; n = 31) in which providing timely video recordings were reinforced with no requirement to reduce breath CO. Results revealed that participants in the AT condition reduced their breath CO levels significantly more so during treatment than participants in the CT condition. Within-group comparisons revealed that participants in both conditions significantly reduced their breath CO, self reported smoking, and nicotine dependence ratings during treatment. However, only participants in the AT condition significantly reduced urinary cotinine levels during treatment, and only participants in this condition maintained all reductions until 6-week post treatment. Participants in the CT condition only maintained self-reported smoking reductions until posttreatment assessments. These results support the feasibility and initial efficacy of this incentive based approach to smoking cessation with adolescent smokers living in rural locations. PMID- 26280593 TI - An event-level investigation of hangovers' relationship to age and drinking. AB - Animal and human data suggest that adolescents experience hangover effects that are distinct from adults. The present study used ecological momentary assessment (EMA) methods to examine the temporal relationships between drinking and hangovers, and how this varied by age and sex. We hypothesized that alcohol's dose-dependent effects on hangover severity are more pronounced among adolescents and young adults than older drinkers. We also explored whether greater hangover severity would lead to a lower likelihood and volume of alcohol use later the same day. Data were pooled from 4 studies of drinkers (N = 274; ages 15 to 66 years) who completed a 4- to 14-day (M = 7.46, SD = 1.13) EMA monitoring period. Each morning, participants recorded how much alcohol they consumed the day before and rated their hangover severity. Participants who consumed a greater quantity of alcohol the prior day reported more severe hangover symptoms; however, there was an interaction between drinking volume and age, such that hangover was more severe among younger drinkers, especially at higher drinking levels. More severe hangover symptoms did not predict the likelihood of drinking later that day; however, on drinking days, more severe hangover symptoms predicted lower quantities of alcohol use later that day. This event-level effect did not vary as a function of age. Study outcomes did not vary by sex. Our findings suggest that younger drinkers experience more severe hangovers, and that greater hangover results in lighter drinking later that same day regardless of age. PMID- 26280594 TI - Upregulation of Collagen Expression via PPARbeta/delta Activation in Aged Skin by Magnesium Lithospermate B from Salvia miltiorrhiza. AB - This study investigated the agonistic activity of magnesium lithospermate B (1), isolated from Salvia miltiorrhiza, on peroxisome proliferator-activated receptor (PPARbeta/delta) and the expressions of collagen genes (COL1A1 and COL3A1) and transforming growth factor-beta1 (TGF-beta1) in models of skin aging. The action of compound 1 as a PPARbeta/delta agonist was determined by reporter gene assay, immunostaining, and Western blotting. To determine the antiaging effects of compound 1 on skin, aged Sprague-Dawley rat skin and ultraviolet B (UVB) irradiated human skin fibroblasts were used. The results show that 1 presented a marked enhancement of both nuclear protein levels and activity of PPARbeta/delta in fibroblasts. In addition, 1 prevented downregulation of PPARbeta/delta activity in aged rat skin and UVB-induced fibroblasts. Furthermore, 1 increased the expressions of COL1A1, COL3A1, and TGF-beta1 in vivo and in a cell culture system. Therefore, the present study shows that compound 1 prevents collagen degradation in aged rat skin and UVB-exposed fibroblasts through PPARbeta/delta activation. The therapeutic and cosmetic applications of compound 1 need further investigation. PMID- 26280595 TI - Asymmetries of amyloid-beta burden and neuronal dysfunction are positively correlated in Alzheimer's disease. AB - Clinical Alzheimer's disease affects both cerebral hemispheres to a similar degree in clinically typical cases. However, in atypical variants like logopenic progressive aphasia, neurodegeneration often presents asymmetrically. Yet, no in vivo imaging study has investigated whether lateralized neurodegeneration corresponds to lateralized amyloid-beta burden. Therefore, using combined (11)C Pittsburgh compound B and (18)F-fluorodeoxyglucose positron emission tomography, we explored whether asymmetric amyloid-beta deposition in Alzheimer's disease is associated with asymmetric hypometabolism and clinical symptoms. From our database of patients who underwent positron emission tomography with both (11)C Pittsburgh compound B and (18)F-fluorodeoxyglucose (n = 132), we included all amyloid-positive patients with prodromal or mild-to-moderate Alzheimer's disease (n = 69). The relationship between (11)C-Pittsburgh compound B binding potential and (18)F-fluorodeoxyglucose uptake was assessed in atlas-based regions of interest covering the entire cerebral cortex. Lateralizations of amyloid-beta and hypometabolism were tested for associations with each other and with type and severity of cognitive symptoms. Positive correlations between asymmetries of Pittsburgh compound B binding potential and hypometabolism were detected in 6 of 25 regions (angular gyrus, middle frontal gyrus, middle occipital gyrus, superior parietal gyrus, inferior and middle temporal gyrus), i.e. hypometabolism was more pronounced on the side of greater amyloid-beta deposition (range: r = 0.41 to 0.53, all P < 0.001). Stronger leftward asymmetry of amyloid-beta deposition was associated with more severe language impairment (P < 0.05), and stronger rightward asymmetry with more severe visuospatial impairment (at trend level, P = 0.073). Similarly, patients with predominance of language deficits showed more left-lateralized amyloid-beta burden and hypometabolism than patients with predominant visuospatial impairment and vice versa in several cortical regions. Associations between amyloid-beta deposition and hypometabolism or cognitive impairment were predominantly observed in brain regions with high amyloid-beta load. The relationship between asymmetries of amyloid-beta deposition and hypometabolism in cortical regions with high amyloid-beta load is in line with the detrimental effect of amyloid-beta burden on neuronal function. Asymmetries were also concordant with lateralized cognitive symptoms, indicating their clinical relevance. PMID- 26280596 TI - GABAergic inhibition shapes interictal dynamics in awake epileptic mice. AB - Epilepsy is characterized by recurrent seizures and brief, synchronous bursts called interictal spikes that are present in-between seizures and observed as transient events in EEG signals. While GABAergic transmission is known to play an important role in shaping healthy brain activity, the role of inhibition in these pathological epileptic dynamics remains unclear. Examining the microcircuits that participate in interictal spikes is thus an important first step towards addressing this issue, as the function of these transient synchronizations in either promoting or prohibiting seizures is currently under debate. To identify the microcircuits recruited in spontaneous interictal spikes in the absence of any proconvulsive drug or anaesthetic agent, we combine a chronic model of epilepsy with in vivo two-photon calcium imaging and multiunit extracellular recordings to map cellular recruitment within large populations of CA1 neurons in mice free to run on a self-paced treadmill. We show that GABAergic neurons, as opposed to their glutamatergic counterparts, are preferentially recruited during spontaneous interictal activity in the CA1 region of the epileptic mouse hippocampus. Although the specific cellular dynamics of interictal spikes are found to be highly variable, they are consistently associated with the activation of GABAergic neurons, resulting in a perisomatic inhibitory restraint that reduces neuronal spiking in the principal cell layer. Given the role of GABAergic neurons in shaping brain activity during normal cognitive function, their aberrant unbalanced recruitment during these transient events could have important downstream effects with clinical implications. PMID- 26280597 TI - Rhesus monkeys (Macaca mulatta) adaptively adjust information seeking in response to information accumulated. AB - Metacognition consists of monitoring and control processes. Monitoring has been inferred when nonhumans use a "decline test" response to selectively escape difficult test trials. Cognitive control has been inferred from selective information-seeking behavior by nonhumans ignorant of needed knowledge. Here we describe a computerized paradigm that extends previous work and assesses dynamic interactions between monitoring and control. Monkeys classified images as containing birds, fish, flowers, or people. To-be-classified images were initially masked, and monkeys were trained to gradually reveal the images by touching a "reveal button." Monkeys could choose to classify images at any time or to reveal more of the images. Thus, they had the opportunity to assess when enough of an image had been revealed to support accurate classification. In Experiment 1, monkeys made more reveal responses before classifying when smaller amounts of the image were revealed by each button touch. In Experiment 2, to-be classified images were shrunk and covered by 1 critical blocker among other blockers that did not provide information when removed. Monkeys made more reveal responses as the critical blocker was removed later in the trial. In Experiment 3, monkeys were presented with previously classified images with either more or fewer blockers obscuring the image than was the case when they chose to classify that image previously. Monkeys made more reveal responses when information was insufficient than when it was excessive. These results indicate that monkeys dynamically monitor evolving decision processes and adaptively collect information as necessary to maintain accuracy. PMID- 26280598 TI - Quantitative fluorine NMR to determine carbohydrate density on glyconanomaterials synthesized from perfluorophenyl azide-functionalized silica nanoparticles by click reaction. AB - A quantitative fluorine NMR ((19)F qNMR) method was developed to determine the carbohydrate density on glyconanomaterials. Mannose (Man)- and galactose (Gal) conjugated silica nanoparticles (SNPs) were synthesized from perfluorophenyl azide (PFPA)-functionalized SNPs and propargylated Man or Gal by copper-catalyzed azide-alkyne cycloaddition (click reaction). After treating PFPA-SNPs or Man-SNPs with hydrofluoric acid followed by lyophilization, the remaining residues were directly subjected to (19)F NMR analysis. The density of PFPA on PFPA-SNP was determined to be 7.7 +/- 0.2 * 10(-16) nmol/nm(2) and Man on Man-SNP to be 6.4 +/ 0.2 * 10(-16) nmol/nm(2) giving a yield of ~83% for the click coupling reaction. The apparent dissociation constant (Kd) of Man-SNPs with fluorescein isothiocyanate (FITC)-concanavalin A (Con A) was determined using a fluorescence competition assay to be 0.289 +/- 0.003 MUM, which represents more than 3 orders of magnitude affinity increase compared to free Man with Con A. PMID- 26280599 TI - Speciation of the Potential Antitumor Agent Vanadocene Dichloride in the Blood Plasma and Model Systems. AB - The speciation of the potential antitumor agent vanadocene dichloride ([Cp2VCl2], abbreviated with VDC) in the blood plasma was studied by instrumental (EPR, ESI MS, MS-MS, and electronic absorption spectroscopy) and computational (DFT) methods. The behavior of VDC at pH 7.4 in aqueous solution, the interaction with the most important bioligands of the plasma (oxalate, carbonate, phosphate, lactate, citrate, histidine, and glycine among those with low molecular mass and transferrin and albumin between the proteins) was evaluated. The results suggest that [Cp2VCl2] transforms at physiological pH to [Cp2V(OH)2] and that only oxalate, carbonate, phosphate, and lactate are able to displace the two OH(-) ions to yield [Cp2V(ox)], [Cp2V(CO3)], [Cp2V(lactH(-1))], and [Cp2V(HPO4)]. The formation of the adducts with oxalate, carbonate, lactate, and hydrogen phosphate was confirmed also by ESI-MS and MS-MS spectra. The stability order is [Cp2V(ox)] ? [Cp2V(CO3)] > [Cp2V(lactH(-1))] > [Cp2V(HPO4)]. No interaction between VDC and plasma proteins was detected under our experimental conditions. Several model systems containing the bioligands (bL) in the same relative ratio as in the blood samples were also examined. Finally, the speciation of VDC in the plasma was studied. The results obtained show that the model systems behave as the blood plasma and indicate that when V concentration is low (10 MUM) VDC is transported in the bloodstream as [Cp2V(ox)]; when V concentration is high (100 MUM) oxalate binds only 9.2 MUM of [Cp2V](2+), whereas the remaining part distributes between [Cp2V(CO3)] (main species) and [Cp2V(lactH(-1))] (minor species); and when V concentration is in the range 10-100 MUM [Cp2V](2+) distributes between [Cp2V(ox)] and [Cp2V(CO3)]. PMID- 26280600 TI - International consensus on periprosthetic joint infection. PMID- 26280601 TI - International consensus on periprosthetic joint infection. AB - The purpose of this manuscript is to document results and complications of use of a regenerative dermal matrix skin substitute for coverage of extremity wounds. A retrospective review at 3 institutions identified 28 patients and 34 wounds who had undergone use of this material (Integra). Complications included failure in two patients (4 wounds). However, overall "take" of the regenerative matrix was 86.1%. In most cases, a split thickness skin graft was applied on average at 25 days following the initial procedure. Failures were associated with infection and irradiation of the surgical field. In this series, use of the dermal regenerative matrix was associated with a high rate of success for wound coverage, obviating the need for flap coverage or prolonged dressing changes in most cases. Further series are likely to refine the known indications and contraindications to use of this method. PMID- 26280602 TI - Evaluation of prominence of straight plates and precontoured clavicle plates using automated plate-to-bone alignment. AB - Hardware prominence after plate fixation for clavicle fracture is a common complication. The aim of the study was to perform a 3D analysis of the prominence of different types of superior clavicle plates. An automated fitting of 3 straight and 10 precontoured plates was performed on 52 3D-CT-scan reconstructed cadaver clavicles. The mean and maximum bone-plate distance and maximum prominence was significant higher with the straight plates compared to the precontoured plates. The mean and maximum boneplate distance was significant higher with the precontoured DePuy-Synthes plates compared to the precontoured Acumed plates but when evaluating the maximum prominence there was no significant difference between the most commonly used 8-holes plates. To conclude, precontoured plates of the clavicula diminish significantly hardware prominence. There exists a difference in hardware prominence between different brands of precontoured plates but this difference is limited and in most cases not significant. PMID- 26280604 TI - Reversed Revised: What to do when it goes wrong? AB - Reversed total shoulder arthroplasty (RTSA) has well known indications and good to excellent results are described in the literature. When the arthroplasty fails however, revision remains a technical challenge with many questions unanswered. To analyse retrospectively and consecutively the indications and results of primary RTSA-revision. All patients that underwent revision RTSA between 2004 and 2009 were included. Indications for surgery, surgical details and clinical evaluation with the preand postoperative Constant-score (CS) were analyzed. 37 Revisions (37 patients) of RTSA were analysed with an average follow up of 41.2 months (24-84). Indications were infection (23), glenoid loosening (9), instability (2) malpositioning (2) and suprascapular nerve irritation (1). 25 patients obtained a one-stage conversion to a new reversed prosthesis; 4 patients obtained a two-stage revision; 8 patients got a megahead prosthesis. No difference in reinfection rate is seen between one- and two stage techniques. An overall lower CS is seen for the mega-head prosthesis. CONCLUSIONS: The main indication for revision was infection. Revision of RTSA to a new reversed prosthesis is to prefer even when several procedures are necessary in one patient. When this is impossible, a mega-head prosthesis is to consider and gives reasonable results. PMID- 26280603 TI - Reduction and internal fixation for acute midshaft clavicular fractures by mini incision using cannulated screws. AB - Open reduction and internal fixation of fracture clavicle has typically been done by variable types of plates. Plates carry the disadvantages of longer incisions, prominence of the plates and wound complications. The purpose of this study is to present an alternative surgical technique for acute midshaft clavicular fracture using cannulated 6.5 screws with minimal incision over the fracture site. Twenty seven adult patients with acute midshaft clavicular fractures were surgically treated with mini open technique using 6.5mm cannulated screws. The modified shoulder rating scale by Chuang was used for outcome evaluation. Union occurred in a mean of 8.3 weeks range 6-12 weeks. Restoration of clavicular length was achieved in all cases. Twenty-four patients experienced no pain on all activity at latest follow-up. All patients expressed their willingness to have the surgery again should they have the same problem. One patient stated that she would not have the surgery again. CONCLUSION: reduction and internal fixation with a cannulated screw is an alternative economic technique for the treatment of acute midshaft clavicular fractures that is useful in selected cases where surgery is indicated. PMID- 26280605 TI - Evaluating the success of preoperative imaging for diagnosing rotator cuff tears in a regional centre. AB - To review the diagnostic performance of ultrasonography (US) and magnetic resonance imaging (MRI) for the detection of rotator-cuff tears, we performed a retrospective audit of patients who underwent shoulder arthroscopy at Hinchingbrooke hospital. The diagnostic accuracies of US for full and partial thickness tears were 82% and 28% respectively. Those of MRI were 82% and 81% respectively. These were lower than expected from the literature. This discrepancy is likely to be the consequence of over-diagnosis in imaging and under-diagnosis at arthroscopy. PMID- 26280606 TI - Carpal Tunnel Syndrome etiology update: where do we stand? PMID- 26280607 TI - Cup positioning in total hip arthroplasty. AB - The "optimal" positioning of the cup in total hip arthroplasty can improve hip function and reduce wear, impingement and dislocation. The cup position is described as the spatial relation between the hip rotation centre and the pelvis and, as the cup orientation around the rotation centre. The first parameter affects hip balance and, if not managed properly, might result in poor function and leg length discrepancy. The second parameter is often "silent", unless impingement or dislocation occurs. However, inappropriate cup orientation can accelerate wear and cause early failure. As such, it is mandatory to get both right, taking into account multiple parameters: the stem position, the approach, the bearing surface, the cup coverage and the pelvic orientation during loading. In most cases a "standard" cup position is adequate. However, specific anatomic features might require an individualized approach. This paper aims at reviewing the parameters that impact on the optimal cup position. This should allow for more judicious choices in those particular cases. PMID- 26280608 TI - Total hip arthroplasty in Belgium: the contribution of a social health insurer to the debate. AB - This study describes current clinical practice and outcomes of Total Hip Arthroplasty in Belgian hospitals. Orthopaedic registries concentrate on implant related analyses and sometimes on patient reported outcomes. Our aim was to describe the extent and to generate hypotheses about the determinants of the variability of health care practices and of prosthesis survival in Belgium. Only unilateral elective primary Total Hip Arthroplasties were included. Length of stay, costs, transfusion rates and other care activities were analysed over 2008 and 2009 together. Prosthesis survival was studied using Kaplan-Meier and Cox regression hazard ratio computations over the period 2000-2009. 36798 elective Total Hip Arthroplasties have been included in a study of all members of the Belgian Christian Sickness Fund. The non-standardised ten year Total Hip Arthroplasty survival rate is 93% (Kaplan-Meier). Quality has progressed notably compared with 10 years earlier. Important variations still persist though between hospitals, for all studied indicators. PMID- 26280609 TI - Re-revision of failed revision Total Hip Arthroplasty acetabular components. AB - While revision of total hip arthroplasty (THA) is being performed with increasing frequency, outcomes of repeated revisions have been rarely reported in the literature. The purpose of this study was to report mid-term outcomes of re revision of failed revision THA acetabular components. We performed at least two revisions of the failed acetabular component in 57 patients (57 hips) between August 1996 and April 2008. Of these, 15 patients with infection were excluded and one died before 4-year evaluation. The final study cohort consisted of 41 patients (41 hips) with a mean age of 55.5 years (range, 37 to 82). Preoperative acetabular bone defects was classified as Paprosky Type IIA in 4 hips, Type IIB in 6, Type IIC in 9, Type IIIA in 16, and Type IIIB in 6. The mean duration of follow-up was 7.2 years (range, 4 to 15). Mean Harris hip score improved 45 points preoperatively to 83 points postoperatively. Six hips (14.6%) required additional revision procedure: 3 for aseptic loosening, 2 for deep infection, and 1 for recurrent instability. Complications included 2 dislocations and 1 peroneal nerve palsy. Kaplan-Meier survivorship with an end point of reoperation for any reason was 88.5% (95% CI, 78.0% to 100%) at 7.2 years. For aseptic loosening of the acetabular component, the survival was 91.8% (95% CI, 80.8% to 100%) at 7.2 years. Rerevision with contemporary uncemented cup or antiprotrusio cage for failed revision THA acetabular components showed encouraging mid-term outcomes for this technically challenging condition. PMID- 26280610 TI - Shape memory embracing fixator for Vancouver type B and type C periprosthetic femoral fractures. AB - The purpose of this study was to analyze clinical and radiographical results of a group of patients with periprosthetic femoral fractures treated with the shape memory embracing fixator. We retrospectively reviewed twelve patients in whom a total of twelve periprosthetic femoral fractures were treated with the shape memory embracing fixator between August 2004 and February 2013. The patients were 3 men and 9 women (mean age, 69.9 years; range 42-92 years). The average duration of follow-up was 39.3 months (range 4-103 months). In one case, bone grafting was used. Postoperative evaluation was based on radiographs and Harris hip scores. All fractures healed at on average 4.4 months (range: 3 to 6 months) after surgery. None of the patients developed nonunion or malunion during the follow up. And there was no implant failure and no infection during follow up. The average Harris hip score at the final follow-up examination was 84.8 points. Results show that the shape memory embracing fixator is a safe and effective means for Vancouver type B and type C periprosthetic femoral fractures following hip arthroplasty. PMID- 26280611 TI - Primary total hip arthroplasty with hydroxyapatite coated titanium femoral stems. Does design philosophy influence long term outcome?: Results of a prospective randomised controlled trial with follow-up of 10-15 years. AB - We present results of a prospective randomised controlled trial examining two cohorts of patients treated with proximally (Group A) and fully coated (Group B) femoral components with long term follow up. Patients were reviewed preoperatively and 6, 12, 26 and 52 weeks post operatively then annually. The Merle d'Aubigne Postel (MDP) hip score was used to assess clinical outcome. A Visual Analog Score (VAS) was also recorded. Statistical calculation was performed using the student's t- test and Kaplan Meier survival analysis. One hundred and four patients were included in group A and 103 patients in group B. Mean age was 60.4 years and 60.8 years respectively. Mean follow- up was 12.9 years. Mean pre-operative MDP scores were 8.8 and 9.5 in Groups A and B respectively. Mean pre-operative VAS score 7.8 and 7.4 respectively. At final follow up mean MDP and VAS were 16.9, 16.6 and 2.1, 2.4 respectively. Three femoral revisions occurred in Group A. Seven revisions occurred in Group B. Survival of the femoral component with revision for any reason as the end point was 96% in Group A and 94.8% in Group B. Both components produced symptomatic relief and similar revision rates. Thigh pain occurred only in Group A. PMID- 26280612 TI - Treatment of distal femur fractures with locking plates: Comparison of periprosthetic fractures above total knee arthroplasty and non-periprosthetic fractures. AB - The purpose of the present study was to compare the results and plate fit of periprosthetic and non-periprosthetic distal femur fractures fixed with locking plates. Twenty-one periprosthetic fractures above a TKA and 27 non-periprosthetic fractures were retrospectively reviewed. The primary healing rate, bone union time, clinical and radiographic results, complications, and additional surgeries were compared between the two groups. The quality of the plate fit on the bone was also compared. There were no differences in the primary healing rate, bone union time, clinical and radiographic results between the two groups. The incidence of overall complication and additional surgeries did not differ (3/21 vs. 5/27, 1/21 vs. 4/27). Plate fit trouble was observed more frequently in periprosthetic fractures (10/21 vs. 1/27, p = 0.004). Fixation of distal femur fractures with locking plates provided satisfactory results with a low risk of complications and additional surgeries in both periprosthetic and non periprosthetic fractures. PMID- 26280613 TI - Can anterior cruciate ligament reconstruction be performed routinely in day clinic? AB - Anterior cruciate ligament reconstruction is performed as an outpatient procedure in selected cases. Whether it can be safely performed on a routine basis in day clinic remains unclear. Our hypothesis was that routinely performing outpatient anterior cruciate ligament reconstruction would be equally safe as compared to inpatient procedures. A cohort of 355 patients who underwent outpatient primary reconstruction was analysed at an average follow-up of 3.8 years. Four patients (1.1%) could not be discharged or were readmitted within 24 hours. The 1-month readmission rate was 1.4%. The overall complication rate was 12.1% (43 cases) of which 4.2% (15 patients) occurred within the first 30 days. Performing anterior cruciate ligament reconstructions routinely in day clinic is associated with almost negligible readmission rates and has similar complication rates as for standard in-hospital anterior cruciate ligament reconstructions. Outpatient anterior cruciate ligament reconstructions can therefore be safely performed without specific preoperative patient selection protocols. PMID- 26280614 TI - Hip resurfacing arthroplasty: A new method to assess and quantify learning phase. AB - Hip resurfacing had initially gained acceptance and popularity as it helps preserve femoral bone stock. In this study we tried to answer the following questions; 1. Whether there is a learning curve for hip resurfacing? 2. Is it present in surgeons from non-developer centres? 3. Is it present in surgeons from developer centres as well? The Oswestry outcome centre was setup to serve an independent international registry for collecting, analysing and reporting outcomes following hip resurfacing. Over a 10 year period, 4535 patients (5000 hips) were recruited from different countries and within the UK from different centres in this study by 139 surgeons from 37 different countries. Our study has shown that function can be used to assess the level of surgical competence. The results from this multilevel analysis have helped to answer the questions posed in the introduction. Hip resurfacing is a surgical procedure with a learning phase and this learning effect is more pronounced in non-developer surgeons as compared to developer surgeons. Hip scores can be used to assess proficiency and competence of surgeons undertaking hip resurfacing arthroplasty. PMID- 26280615 TI - Meniscal transplantation: still experimental surgery? A review. AB - INTRODUCTION: The objective of this review is to give a state of affairs of meniscal transplantation, with the accent on preservation and surgical techniques. MATERIALS AND METHODS: All articles were selected by performing a search on the literature by using relevant keywords. The most relevant articles were selected with close attention to the publication date. RESULTS: When a meniscal tear is diagnosed, suture can be an option in the vascular zone, whereas the more frequently affected avascular zone heals poorly. A meniscectomy however is not without consequences, wherefore meniscal transplantation can be seen as a therapeutic option for pain reduction and improvement of function when the meniscus is lost. The meniscal scaffold, allograft and autograft can be currently withheld as possible grafts, where the meniscal scaffolds hold great promise as an alternative to the allograft. Various fixation techniques are therefore developed, where viable, deep frozen as well as cryopreservated allografts seem to give the most promising short term results. The transplantation can be performed using an open as well as an arthroscopic technique, using soft tissue fixation, bone plugs or blocks. De primacy of one technique can't be proven. In general meniscal transplantation can be considered as an acceptable procedure. DISCUSSION: Since the outcomes of different studies are difficult to compare, an attempt should be made to limit new studies to the comparison of one aspect. We can conclude that larger, more comparative randomised controlled long-term studies are necessary to resolve which techniques can give the best long-term results. PMID- 26280616 TI - Medial malleolar screw hemiepiphysiodesis for ankle valgus in children with spina bifida. AB - Medial malleolar screw hemiepiphysiodesis has been shown to be an effective procedure for the treatment of ankle valgus in children with spina bifida. The purpose of this study was to highlight the guided growth technique and discuss its efficacy. We retrospectively reviewed 10 spina bifida patients with 18 ankle valgus deformities treated with medial malleolar screw hemiepiphysiodesis. Medical reports were obtained to document age at surgery, gender, concurrent operative procedures and postoperative early and late complications. Anteroposterior and lateral weight bearing radiographs of both ankles were evaluated using the tibiotalar angle, pre and postoperatively. The average age at operation was 10.05 years. Average follow up was 15.33 months (11-21 months). During follow-up, the average preoperative distal tibiotalar angle of 16.27 degrees improved to an average of 2.88 degrees with statistical significance (p < 0.05). No major complications were detected. In conclusion, hemiepiphysiodesis is a safe and sufficient method to correct ankle valgus deformity in children with spina bifida, with a low incidence. PMID- 26280617 TI - The role of Taylor Spatial Frame for the treatment of acquired and congenital tibial deformities in children. AB - This study evaluates the use of the Taylor Spatial Frame (TSF) for the correction of acquired and congenital tibial deformities in children. The purpose is to underline problems, obstacles and complications that can be observed during treatment to reveal the learning curve and potential risk factors and to propose solutions to avoid difficulties during its use 86 tibia deformities were corrected in 66 children during a period of 7 years and were classified according to anatomical and dominant type of deformity. Follow up was 54.2 months. Gradual correction was performed according to the individualized time schedule. We faced 42 difficulties: 29 problems, 10 obstacles and 3 complications, distributed across all years. Significant correlation was found between patient's age and number of difficulties. The incidence of the difficulties was equally spread over the different etiologies, but it was statistically significant across the years. Proximal tibia and complex multi-plane deformities seem to be related to an increased incidence of postoperative difficulties. TSF can yield accurate results, is easy to handle and provides an excellent concomitant 3-direction correction. PMID- 26280619 TI - The management of myxofibrosarcoma - a ten-year experience in a single specialist centre. AB - The aim of this study was to assess the management of myxofibrosarcoma in a single specialist centre, and examine factors contributing to local recurrence, metastasis and patient survival. Retrospective analysis of the referral, diagnosis, and management were obtained. Outcome measures including local recurrence, metastasis and death were recorded. 30 patients (mean age of 65.8 years) were treated for myxofibrosarcoma with limb salvage surgery between January 2003 and July 2012. 25 patients were treated for primary disease. Mean follow-up was 49 months (range 10-122). Larger tumours were most likely to metastasise (p = 0.041). Tumour size, resection margin and grade did not predict local recurrence or death. Local recurrence developed in eight patients (26.7%) with six subsequently requiring amputation, and four patients (16.7%) developed metastasis. Our results regarding local control and patient survival compare with that of the literature regarding limb salvage for primary disease, but amputation may be required for recurrent disease. PMID- 26280618 TI - The treatment of infected tibial nonunion by bone transport using the Ilizarov external fixator and a systematic review of infected tibial nonunion treated by Ilizarov methods. AB - BACKGROUND: This study was designed to evaluate the effectiveness of the treatment of infected tibial nonunion by bone transport using the Ilizarov external fixator. We retrospectively reviewed 66 patients with infected tibial nonunion treated by bone transport using the Ilizarov external fixator. Our study included 62 males and 4 females with a mean of age 37.06 years. The average length of the bone defects after radical debridement was 6.27 cm (range 3-13 cm). The mean follow-up after removal of the apparatus was 25.91 months (18-46 months). 6 patients were lost to follow-up. All the patients achieved bone union and no recurrence of infection was observed. The mean external fixation index was 1.38 months/cm (range 1.15-1.58 months/cm). According to Association for the Study and Application of the Method of Ilizarov (ASAMI) classification, bone results were excellent in 44, good in 15, fair in 5 and poor in 2; functional results were excellent in 24, good in 26, fair in 10 and no poor. CONCLUSIONS: CONCLUSIONS: Our study and the current evidence suggested that Ilizarov methods in the treatment of infected tibial nonunion acquired satisfied effects in bone results and functional results. Radical debridement is the key step to control bone infection. PMID- 26280620 TI - Drugging the Ral GTPase. AB - The RAL GTPases have emerged as important drivers of tumor growth and metastasis in lung, colon, pancreatic and other cancers. We recently developed the first small molecule inhibitors of RAL that exhibited antitumor activity in human lung cancer cell lines. These compounds are non-competitive inhibitors that bind to the allosteric site of GDP-bound RAL. The RAL inhibitors have the potential to be used in combination therapy with other inhibitors of the RAS signaling pathway. They also provide insights toward directly targeting other GTPases. PMID- 26280622 TI - Guiding of Electrons in a Few-Mode Ballistic Graphene Channel. AB - In graphene, the extremely fast charge carriers can be controlled by electron optical elements, such as waveguides, in which the transmissivity is tuned by the wavelength. In this work, charge carriers are guided in a suspended ballistic few mode graphene channel, defined by electrostatic gating. By depleting the channel, a reduction of mode number and steps in the conductance are observed, until the channel is completely emptied. The measurements are supported by tight-binding transport calculations including the full electrostatics of the sample. PMID- 26280621 TI - Materials from Mussel-Inspired Chemistry for Cell and Tissue Engineering Applications. AB - Current advances in biomaterial fabrication techniques have broadened their application in different realms of biomedical engineering, spanning from drug delivery to tissue engineering. The success of biomaterials depends highly on the ability to modulate cell and tissue responses, including cell adhesion, as well as induction of repair and immune processes. Thus, most recent approaches in the field have concentrated on functionalizing biomaterials with different biomolecules intended to evoke cell- and tissue-specific reactions. Marine mussels produce mussel adhesive proteins (MAPs), which help them strongly attach to different surfaces, even under wet conditions in the ocean. Inspired by mussel adhesiveness, scientists discovered that dopamine undergoes self-polymerization at alkaline conditions. This reaction provides a universal coating for metals, polymers, and ceramics, regardless of their chemical and physical properties. Furthermore, this polymerized layer is enriched with catechol groups that enable immobilization of primary amine or thiol-based biomolecules via a simple dipping process. Herein, this review explores the versatile surface modification techniques that have recently been exploited in tissue engineering and summarizes polydopamine polymerization mechanisms, coating process parameters, and effects on substrate properties. A brief discussion of polydopamine-based reactions in the context of engineering various tissue types, including bone, blood vessels, cartilage, nerves, and muscle, is also provided. PMID- 26280624 TI - Arginine-glycine-aspartic acid functional branched semi-interpenetrating hydrogels. AB - For the first time a series of functional hydrogels based on semi interpenetrating networks with both branched and crosslinked polymer components have been prepared and we show the successful use of these materials as substrates for cell culture. The materials consist of highly branched poly(N isopropyl acrylamide)s with peptide functionalised end groups in a continuous phase of crosslinked poly(vinyl pyrrolidone). Functionalisation of the end groups of the branched polymer component with the GRGDS peptide produces a hydrogel that supports cell adhesion and proliferation. The materials provide a new synthetic functional biomaterial that has many of the features of extracellular matrix, and as such can be used to support tissue regeneration and cell culture. This class of high water content hydrogel material has important advantages over other functional hydrogels in its synthesis and does not require post-processing modifications nor are functional-monomers, which change the polymerisation process, required. Thus, the systems are amenable to large scale and bespoke manufacturing using conventional moulding or additive manufacturing techniques. Processing using additive manufacturing is exemplified by producing tubes using microstereolithography. PMID- 26280626 TI - Samuel Baron (1928-2015). PMID- 26280625 TI - Biomaterials for mRNA delivery. AB - Messenger RNA (mRNA) has recently emerged with remarkable potential as an effective alternative to DNA-based therapies because of several unique advantages. mRNA does not require nuclear entry for transfection activity and has a negligible chance of integrating into the host genome which excludes the possibility of potentially detrimental genomic alternations. Chemical modification of mRNA has further enhanced its stability and decreased its activation of innate immune responses. Additionally, mRNA has been found to have rapid expression and predictable kinetics. Nevertheless, the ubiquitous application of mRNA remains challenging given its unfavorable attributes, such as large size, negative charge and susceptibility to enzymatic degradation. Further refinement of mRNA delivery modalities is therefore essential for its development as a therapeutic tool. This review provides an exclusive overview of current state-of-the-art biomaterials and nanotechnology platforms for mRNA delivery, and discusses future prospects to bring these exciting technologies into clinical practice. PMID- 26280627 TI - Case-based update: primary intraventricular brain abscess in a 10-year-old child. AB - BACKGROUND: Intraventricular abscesses are very rare and usually result from secondary rupture of a brain abscess. In the few published cases, clinical presentation was subacute and different pathogens were found. The diagnosis might be mistaken as an intraventricular tumor. CASE REPORT: This is a case of a 10 year-old girl suffering from cyanotic heart disease that was presented with subacute onset of headache, vomiting, and some signs of inflammation. Symptoms lead to early brain imaging (CT/MRI) demonstrating left ventricular horn lesion affecting adjacent brain structures. Neuroradiologists suspected an intraventricular tumor, but cardiac history and signs of inflammation led to lumbar puncture and evidence of CNS infection, and intraventricular abscess was suspected. Navigated aspiration was performed, and multi-sensitive Eikenella corrodens was cultivated. Broad antibiotic treatment and dexamethasone were initiated, and symptoms disappeared. Follow-up imaging demonstrated gradual regression of the intraventricular abscess. The girl underwent regular professional teeth cleaning which was discussed as possible cause of infection. CONCLUSIONS: Although an isolated intraventricular abscess is a very rare event, typical predisposing cardiac history together with central nervous symptoms and an intracranial contrasting mass should always lead to the differential diagnosis of a brain abscess and be biopsied first. E. corrodens is a typical organism of the mouth flora, but a rare cause for a brain abscess. Harmless teeth cleaning procedures may cause hematogenic spread and lead to CNS infections, e.g., in patients with predisposing diseases. To our knowledge, there are only six previous reports of primary intraventricular brain abscess. PMID- 26280628 TI - Pre-operative evaluation in pediatric patients with cortical dysplasia. AB - INTRODUCTION: Focal cortical dysplasia (FCD) is an important cause of refractory seizures and catastrophic epilepsy in infants and children who had epilepsy surgery. AIMS OF THE REVIEW: This manuscript will discuss age-related unique clinical characteristics in evaluation of infants and young children because the understanding of these age-related features is critical in selecting children who can benefit from epilepsy surgery. In addition, we will review the non-invasive tools available for the presurgical evaluation of children with FCD and their individual contribution to the formulation of the presurgical hypothesis. PMID- 26280629 TI - The human occipital bone: review and update on its embryology and molecular development. AB - INTRODUCTION: The formation of the occipital bone is intricate and has been extensively studied with many controversial conclusions, but with minimal effort being focused on the genes and molecular interactions necessary for its formation. A better understanding of this bone of the calvarial and skull base may shed light on pathologies where the occiput is often considered the offending entity. METHODS: A review of the germane medical literature using textbooks and standard search engines was performed to gather information about previous conclusions as it pertains to the embryology and ossification of the occipital bone. RESULTS: The occipital bone has both membranous and cartilaginous origin with ossification occurring as early as week 9 of fetal gestation. Its formations is dependent on complex interacts between genes and molecules with pathologies resulting from disruption of this delicate process. CONCLUSION: There has been much controversy in the past in regards to the development and ossification process necessary for occipital bone formation, which has only recently been clarified with documentation of the genes and molecular interactions necessary for its formation. Lastly, this improved knowledge might improve our understanding of such congenital derailments as the Chiari malformations. PMID- 26280630 TI - Perineal pain secondary to tethered cord syndrome: retrospective review of single institution experience. AB - OBJECT: Tethered cord syndrome (TCS) encompasses a spectrum of neurological dysfunction related to excessive tension on the distal spinal cord resulting in anatomic deformation and metabolic disturbance. Symptoms typically manifest as back/leg pain, neurogenic bladder dysfunction, constipation, sphincter abnormalities, and scoliosis. To date, among the least well-described symptoms of TCS is pain or hypersensitivity in the perineal region. The authors reviewed their experience with spinal cord detethering to identify and further characterize those who present with perineal pain or hypersensitivity. METHODS: Cases of spinal cord detethering at a single institution were retrospectively reviewed. Patients were initially identified by procedural codes. Cases were reviewed for presenting symptoms, specifically perineal pain or hypersensitivity. Magnetic resonance image (MRI) findings, clinical outcome, and length of follow up were also noted. RESULTS: Of the 491 patients identified, seven patients (1.4%) were identified as having preoperative perineal pain or hypersensitivity. All of these patients had complete resolution of perineal pain/hypersensitivity at the time of last follow-up. Furthermore, five (71%) of these patients experienced resolution of all initial symptoms. CONCLUSION: Perineal pain or hypersensitivity can be an important symptom of spinal cord tethering. Spinal cord detethering may result in a good outcome and relief of perineal pain or hypersensitivity. PMID- 26280631 TI - Comprehensive anatomical and immunohistochemical review of the innervation of the human spine and joints with application to an improved understanding of back pain. AB - BACKGROUND: Pain of spinal origin contributes significantly to cervical, thoracic, and lower back pain presentations. Such pain originates in the nerve fibers supplying the joints or the surrounding ligaments and intervertebral discs. Although there has been little detailed discussion of spinal bony innervation patterns in the literature, the clinical implications of these patterns are anatomically and medically significant. METHODS: The present review provides a detailed analysis of the innervation of the spine, identifying the unique features of each part via online search engines. CONCLUSIONS: The clinical implications of these various studies lie in the importance of the innervation patterns for the mechanism of spinal pain. Immunohistochemical studies have provided further evidence regarding the nature of the innervation of the spine. PMID- 26280632 TI - Cerebral ventriculomegaly after the bidirectional Glenn (BDG) shunt: a single institution retrospective analysis. AB - PURPOSE: The bidirectional Glenn (BDG) procedure involves the anastomosis of the superior vena cava (SVC) to the pulmonary artery, increasing central venous pressure (CVP). We hypothesize that this increase in CVP triggers an acute neurologic insult, leading to ventriculomegaly. METHODS: In this retrospective analysis in a tertiary care children's hospital, we identified 167 patients who underwent the BDG procedure between August 2006 and July 2013. Within this initial cohort, 24 patients had head imaging (CT, MRI, or ultrasound) performed both before and after the BDG. RESULTS: From head imaging available from these 24 patients, we measured the frontal-occipital horn ratio (FOR), a well-validated measure of lateral ventricle size. Using central venous catheter data, we assessed postoperative CVP at 12, 24, and 48 h. Paired t tests and linear regression were used to evaluate our cohort. Median age at surgery was 4.9 months. Paired analysis revealed that median FOR significantly increased between preoperative (median 0.38, IQR 0.37-0.41) and postoperative (median 0.42, IQR 0.40-0.45) head images (p = 0.005). Increasing change in FOR was associated with increased 12-h (R(2) = 0.369, p = 0.003) but not 24- or 48-h postoperative CVP. CONCLUSIONS: To our knowledge, our study is the first to demonstrate ventriculomegaly developing after the BDG. Physiologically, increasing CVP after the BDG was associated with greater change in lateral ventricle size. This supports the contention that increasing CVP produced during the BDG may damage the developing brain. This study has informed a prospective evaluation of a link between the BDG procedure and neurologic outcomes. PMID- 26280633 TI - Is low b-factors-based apparent diffusion coefficient helpful in assessing renal dysfunction? AB - PURPOSE: To investigate whether low b-factors-based apparent diffusion coefficient (ADC) is helpful in assessing renal dysfunction. MATERIALS AND METHODS: Forty-four subjects were recruited, and classified as having severe renal injury group (sRI) or not (non-sRI) according to a threshold of estimated glomerular filtration rate (eGFR) = 30 ml/min/1.73 m(2). A free-breathing DWI with 7 b-factors (0, 20, 40, 80, 200, 400, and 800 s/mm(2)) was performed. After choosing an anatomical section that covered the largest part of right kidney, the regions of interest covered the renal parenchyma. For each subject, two apparent diffusion coefficients based on all b-factors less than 400 s/mm(2) (ADC0-400) and 800 s/mm(2) (ADC0-800) were calculated by fitting the signal intensity at different b-factors to a mono-exponential decay, respectively. It was found that the examination time of the free-breathing DWI sequence in this study can be reduced from 3.27 to 2.55 min if the b-factor (800 s/mm(2)) is removed. RESULTS: ADC0-400 was larger than ADC0-800 in each group (P < 0.05). Both ADC0-400 and ADC0-800 were smaller in the sRI group than those in the non-sRI group (P < 0.01), and they were linearly related with eGFR (P < 0.05). While a significant difference was not found between the two coefficients to differentiate sRI from non-sRI participants (P > 0.05), a strong correlation was present between ADC0 400 and ADC0-800 (r = 0.856, P < 0.001). CONCLUSION: The low b-factors-based ADC was an economical option for reducing the examination time without sacrificing its diagnostic performance. PMID- 26280634 TI - Building solids inside nano-space: from confined amorphous through confined solvate to confined 'metastable' polymorph. AB - The nanocrystallisation of complex molecules inside mesoporous hosts and control over the resulting structure is a significant challenge. To date the largest organic molecule crystallised inside the nano-pores is a known pharmaceutical intermediate - ROY (259.3 g mol(-1)). In this work we demonstrate smart manipulation of the phase of a larger confined pharmaceutical - indomethacin (IMC, 357.8 g mol(-1)), a substance with known conformational flexibility and complex polymorphic behaviour. We show the detailed structural analysis and the control of solid state transformations of encapsulated molecules inside the pores of mesoscopic cellular foam (MCF, pore size ca. 29 nm) and controlled pore glass (CPG, pore size ca. 55 nm). Starting from confined amorphous IMC we drive crystallisation into a confined methanol solvate, which upon vacuum drying leads to the stabilised rare form V of IMC inside the MCF host. In contrast to the pure form, encapsulated form V does not transform into a more stable polymorph upon heating. The size of the constraining pores and the drug concentration within the pores determine whether the amorphous state of the drug is stabilised or it recrystallises into confined nanocrystals. The work presents, in a critical manner, an application of complementary techniques (DSC, PXRD, solid-state NMR, N2 adsorption) to confirm unambiguously the phase transitions under confinement and offers a comprehensive strategy towards the formation and control of nano crystalline encapsulated organic solids. PMID- 26280635 TI - Appendiceal ultrasound: the importance of conveying probability of disease. PMID- 26280636 TI - Appendiceal ultrasound: the importance of determinacy. PMID- 26280637 TI - Pediatric appendiceal ultrasound: accuracy, determinacy and clinical outcomes. AB - BACKGROUND: Ultrasonography is considered the most appropriate initial imaging study in the evaluation of acute appendicitis in children but has recently come under criticism with reports of low specificity and high indeterminate study rates, particularly when used in obese patients and patients early in the course of their disease, or when performed by sonographers with limited experience. OBJECTIVE: To (1) assess the impact of patient factors (gender, age, body mass index, and symptom duration) and system factors (call status or year of exam) on pediatric appendiceal US accuracy and indeterminate study rate, (2) assess the impact of indeterminate study results on follow-up CT and negative laparotomy rates and (3) present strategies to reduce the rate of indeterminate US studies and improve accuracy. MATERIALS AND METHODS: We retrospectively reviewed all US reports performed for the assessment of acute appendicitis in children <18 years old at Mayo Clinic Rochester from January 2010 to June 2014. RESULTS: A total of 790 US examinations were performed in 452 girls (57%) and 338 boys (43%). The prevalence of appendicitis was 18.5% (146/790). There were 109 true-positive, 440 true-negative, 17 false-positive, 6 false-negative, 218 equivocal and 41 technically inadequate US studies. A definitive interpretation was made in 72% of the studies, with an accuracy, sensitivity and specificity of 0.960, 0.948 and 0.963, respectively. No patient or system factors significantly affected US accuracy. Indeterminate studies (28%) had significantly higher CT utilization (46% vs. 11%) and normal appendectomy rates (6.9% vs. 3.5%). CONCLUSION: US should be the initial imaging study of choice for pediatric appendicitis. When a definitive interpretation was given, the accuracy was 96%, was independent of patient and system factors and resulted in reduced follow-up CTs and negative laparotomies. Accuracy can be increased by requiring the presence of periappendiceal inflammatory changes prior to interpreting a mildly distended appendix as positive for acute appendicitis. The indeterminate study rate can be reduced by not requiring visualization of the normal appendix for the exclusion of acute appendicitis. PMID- 26280638 TI - Development and validation of an ultrasound scoring system for children with suspected acute appendicitis. AB - BACKGROUND: To facilitate consistent, reliable communication among providers, we developed a scoring system (Appy-Score) for reporting limited right lower quadrant ultrasound (US) exams performed for suspected pediatric appendicitis. OBJECTIVE: The purpose of this study was to evaluate implementation of this scoring system and its ability to risk-stratify children with suspected appendicitis. MATERIALS AND METHODS: In this HIPAA compliant, Institutional Review Board-approved study, the Appy-Score was applied retrospectively to all limited abdominal US exams ordered for suspected pediatric appendicitis through our emergency department during a 5-month pre-implementation period (Jan 1, 2013, to May 31, 2013), and Appy-Score use was tracked prospectively post implementation (July 1, 2013, to Sept. 30,2013). Appy-Score strata were: 1 = normal completely visualized appendix; 2 = normal partially visualized appendix; 3 = non-visualized appendix, 4 = equivocal, 5a = non-perforated appendicitis and 5b = perforated appendicitis. Appy-Score use, frequency of appendicitis by Appy Score stratum, and diagnostic performance measures of US exams were computed using operative and clinical finding as reference standards. Secondary outcome measures included rates of CT imaging following US exams and negative appendectomy rates. RESULTS: We identified 1,235 patients in the pre implementation and 686 patients in the post-implementation groups. Appy-Score use increased from 24% (37/155) in July to 89% (226/254) in September (P < 0.001). Appendicitis frequency by Appy-Score stratum post-implementation was: 1 = 0.5%, 2 = 0%, 3 = 9.5%, 4 = 44%, 5a = 92.3%, and 5b = 100%. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 96.3% (287/298), 93.9% (880/937), 83.4% (287/344), and 98.8% (880/891) pre implementation and 93.0% (200/215), 92.6% (436/471), 85.1% (200/235), and 96.7% (436/451) post-implementation - only NPV was statistically different (P = 0.012). CT imaging after US decreased by 31% between pre- and post-implementation, 8.6% (106/1235) vs. 6.0% (41/686); P = 0.048). Negative appendectomy rates did not change (4.4% vs. 4.1%, P = 0.8). CONCLUSION: A scoring system and structured template for reporting US exam results for suspected pediatric appendicitis was successfully adopted by a pediatric radiology department at a large tertiary children's hospital and stratifies risk for children based on their likelihood of appendicitis. PMID- 26280640 TI - Diffusion-weighted imaging and the apparent diffusion coefficient on 3T MR imaging in the differentiation of craniopharyngiomas and germ cell tumors. AB - The apparent diffusion coefficient (ADC) on diffusion-weighted imaging (DWI) plays an important role in diagnosing intracranial tumors and predicting the histopathological grade of the tumor. However, the differences in the ADC values between craniopharyngiomas and germ cell tumors (GCTs) have not been clarified. We therefore evaluated the DWI and ADC values at b = 1000 and b = 4000 s/mm(2) on 3T magnetic resonance (MR) imaging and assessed the possibility of differentiating between craniopharyngiomas and GCTs. We retrospectively reviewed 19 patients with craniopharyngioma and 24 patients with GCT who underwent surgery and received a histopathological diagnosis. Thirty-four patients underwent DWI with b = 1000 and b = 4000 s/mm(2) and nine patients underwent periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) DWI with b = 1000 s/mm(2). The ADC was determined by manually placing regions of interests (ROIs) in the respective tumor regions on the ADC maps and is expressed as the minimum (ADC(MIN)), mean (ADC(MEAN)), and maximum (ADC(MAX)) absolute values. The craniopharyngiomas showed lower intensity on DWI at b = 1000 and b = 4000 s/mm(2) than the GCTs. Furthermore, the craniopharyngiomas demonstrated significantly high ADC values (ADC(MIN), ADC(MEAN), and ADC(MAX)) in comparison with the GCTs on DWI at b = 1000 and b = 4000 s/mm(2). The logistic discriminant analysis clarified the advantage of ADC(MIN) at b = 4000 s/mm(2) in differentiating between craniopharyngiomas and GCTs compared with the other ADC values. DWI and the ADC values may help clinicians to differentiate between craniopharyngiomas and GCTs. The ADC(MIN) at b = 4000 s/mm(2) is particularly useful for differentiation. PMID- 26280641 TI - Peter Henry Dawson, May 28, 1937-June 12, 2015. PMID- 26280639 TI - Hearing loss in hydrocephalus: a review, with focus on mechanisms. AB - While neither hydrocephalus nor cerebrospinal fluid (CSF) shunt placement is traditionally considered in the differential diagnosis of hearing loss, there is substantial evidence that CSF circulation and pressure abnormalities can produce auditory dysfunction. Several indirect mechanisms may explain association between hydrocephalus and hearing loss, including mass effect, compromise of the auditory pathway, complications of prematurity, and genetically mediated hydrocephalus and hearing loss. Nevertheless, researchers have proposed a direct mechanism, which we term the hydrodynamic theory. In this hypothesis, the intimate relationship between CSF and inner ear fluids permits relative endolymphatic or perilymphatic hydrops in the setting of CSF pressure disturbances. CSF is continuous with perilymph, and CSF pressure changes are known to produce parallel perilymphatic pressure changes. In support of the hydrodynamic theory, some studies have found an independent association between hydrocephalus and hearing loss. Moreover, surgical shunting of CSF has been linked to both resolution and development of auditory dysfunction. The disease burden of hydrocephalus-associated hearing loss may be large, and because hydrocephalus and over-shunting are reversible, this relationship merits broader recognition. Hydrocephalic patients should be monitored for hearing loss, and hearing loss in a patient with shunted hydrocephalus should prompt further evaluation and possibly adjustment of shunt settings. PMID- 26280642 TI - "You hoped we would sleep walk into accepting the collection of our data": controversies surrounding the UK care.data scheme and their wider relevance for biomedical research. AB - An 'Information Centre' has recently been established by law which has the power to collect, collate and provide access to the medical information for all patients treated by the National Health Service in England, whether in hospitals or by General Practitioners. This so-called 'care.data' scheme has given rise to major and ongoing controversies. We will sketch the background of the scheme and look at the responses it has elicited from citizens and medical professionals. In Autumn 2013, NHS England set up a care.data website where citizens could record their concerns regarding the collection of health-related data by the Information Centre. We have reviewed all the comments on this website up until June 2015. We have also analysed the readers' comments on the coverage of the care.data scheme in one of the main national UK newspapers. When discussing the responses of citizens, we will make a distinction between the problems that citizens detect and the solutions they propose. The solutions that are being perceived as the most relevant ones can be summarized as follows: citizens wish to further the common good without being manipulated into doing it, while at the same time being safeguarded against various abuses. The issue of trust turns out to figure prominently. Our analysis of reactions to the scheme in no way pretends to be exhaustive, yet it provides various relevant insights into the concerns identified by citizens as well as medical professionals. These concerns, moreover, have a more general relevance in relation to other contexts of medical data-mining as well as biobank research. Our analysis also offers important pointers as to how those concerns might be addressed. PMID- 26280643 TI - [Avulsion of the Globe after Bicycle Accident--Clinical and Histopathological Evaluation]. AB - BACKGROUND: Potential pathological mechanisms and complications of traumatic avulsio bulbi will be discussed based on the history, clinical, and histopathological findings of two patients. HISTORY AND SIGNS: Both patients were heavily affected by alcohol and had a bicycle accident with subsequent perforation of the upper eyelid by the handlebar-mounted hand brake levers. The accident resulted in disruption of the optic nerve and anterior displacement of the globe. THERAPY AND OUTCOME: In one patient, it was possible to reposition the globe into the orbit; however, the second patient's eye had to be enucleated. Functional testing demonstrated permanent loss of vision of the primary involved eyes, visual field defects, and visual impairment of one fellow eye. CONCLUSION: Avulsio bulbi describes a severe trauma to the eye often induced by sport and traffic accidents. Special attention should be addressed to the primary non affected fellow eye with regard to potential functional defects. PMID- 26280644 TI - [Relevant Parameters of Optic Nerve Analysis from Spectral Domain OCT for Glaucoma Diagnostics]. AB - BACKGROUND: In early diagnosis and follow-up of patients with glaucoma anatomic diagnostic examinations have become more important in addition to static perimetry. Patients with open angle glaucoma suffer a slow visual field loss due to the loss of ganglion cells, which these examinations could detect earlier than perimetry can. METHODS: Parameters of the optical coherence tomography (OCT) were analysed in 89 patients (175 eyes) with advanced open angle glaucoma. In a prospective study, the functional findings from static perimetry (HFA-II, 24-2 programme) and the anatomic parameters of optic nerve analysis with SD-OCT (Cirrus-OCT) were evaluated. RESULTS: The results showed a mean deviation (MD) in perimetry of - 8.31 +/- 9.76 dB and in the analysis of the optic nerve head of 71.93 +/- 15.86 um retinal nerve fibre layer (RNFL) as well as 85.54 +/- 28.2 um RNFL for the inferior quadrant, 0.95 +/- 0.46 mm(2) for the rim area and 0.69 +/- 0.18 for the vertical CD ratio. There was a significant correlation (p < 0.05) between MD und RNFL (r = 0.603), as well as RNFL of the inferior quadrant (r = 0.620), rim area (r = 0.552) and average CD ratio (r = - 0.551). The best correlation for the optical nerve head analysis was found between MD and vertical CD ratio (r = - 0.568). CONCLUSIONS: There was a good correlation between functional and anatomic parameters in perimetry and OCT. In particular, the mean and inferior retinal nerve fibre layer thickness, the rim area, and the vertical CD ratio revealed to be significant parameters in glaucomatous eyes. PMID- 26280645 TI - [TGC Repeats in Intron 2 of the TCF4 Gene have a Good Predictive Power Regarding to Fuchs Endothelial Corneal Dystrophy]. AB - BACKGROUND: Fuchs endothelial corneal dystrophy (FECD) is one of the most common indications for corneal transplants. FECD is associated with various genes, e.g., COL8A2 or SLC4A11. Among other things a TGC trinucleotide repeat expansion in intron 2 of the TCF4 gene has been characterised in FECD patients and the allele G of the polymorphism rs613872 in intron 3 of the same gene has been associated with this disease. Our intention was to investigate sources in molecular genetics in the German population and to calculate the odds ratio as indicator for the chance to suffer from FECD. PATIENTS AND METHOD: 42 unrelated FECD patients, 93 unrelated controls and 17 members of a family with four FECD affected patients have been examined for the described changes in the TCF4 gene. After amplification of the TGC repeats with specific PCR the obtained products were electrophoretically divided according to their length and investigated with a triplet-primed PCR. Polymorphism rs613872 was analysed by Sanger sequencing. All coding exons of the adjacent genes TCF4 and LOXHD1 were sequenced in six patients in order to exclude potential disease associated mutations. RESULTS: 33 out of 42 unrelated analysed patients (79 %) had a TGC repeat expansion (> 50 TGC repeats) in intron 2 of the TCF4 gene. Out of 93 controls only 10 (10.8 %) showed an expanded allele. In the family the four diseased and four healthy subjects of the 17 examined family members had an expanded allele. Analysis of the polymorphism rs613872 in intron 3 of the TCF4 gene exhibited 33 of 42 unrelated patients (78.6 %) heterozygous TG and four homozygous GG (9.5 %). 65 of 93 controls were homozygous TT (69.9 %) and only 21 heterozygous TG (22.6 %). Of the 17 family members nine had the genotype TG, including the four FECD patients. Sequencing of the coding exons of TCF4 and LOXHD1 in six patients showed no variant described with FECD. The odds ratio as indicator for being affected by FECD in our data for the expanded TGC allele is 30. The chance of being affected is thus 30 times higher when someone exhibits the expanded allele. For a carrier of the risk allele G the chance is 16.5 times higher. DISCUSSION: An expanded TGC allele with more than 50 TGC repeats in intron 2 and the described risk allele G of the polymorphism rs613872 in intron 3 of the TCF4 gene appear as an association to FECD. The chance to be affected by FECD is up to 30 times higher. With molecular genetics also donors with clinically unknown FECD may be detected. PMID- 26280646 TI - [The Influence of Intravitreal Injections on Outpatient Cataract Operations in Germany]. AB - PURPOSE: The number of outpatient operations in Germany is not registered in a centralised manner. To estimate the development of the outpatient intraocular surgery especially since the implementation of the intravitreal injections, surveys among ophthalmic surgeons were analysed. METHODS: Between 2006 and 2013 surveys were done among ophthalmic surgeons in Germany using questionnaires. An average of 318 completed questionnaires were sent back. The mean participation ratio was 37 %. RESULTS: Between 2006 and 2013 an extrapolated mean of 347 564 cataract operations and 139 946 intravitreal injections were reported. Whereas the number of cataract operations was constant in the observation period, the number of injections increased considerably from 35 135 in 2006 to 274 714 in 2013. CONCLUSION: A saturation in the development of the numbers of the intravitreal injections could not yet be observed. Other outpatient operations, especially cataract procedures were not replaced by the increase of the injections in the recent years. PMID- 26280647 TI - [Fundus Autofluorescence Imaging]. AB - Fundus autofluorescence (FAF) imaging allows for non-invasive mapping of changes at the level of the retinal pigment epithelium/photoreceptor complex and of alterations of macular pigment distribution. This imaging method is based on the visualisation of intrinsic fluorophores and may be easily and rapidly used in routine patient care. Main applications include degenerative disorders of the outer retina such as age-related macular degeneration, hereditary and acquired retinal diseases. FAF imaging is particularly helpful for differential diagnosis, detection and extent of involved retinal areas, structural-functional correlations and monitoring of changes over time. Recent developments include - in addition to the original application of short wavelength light for excitation ("blue" FAF imaging) - the use of other wavelength ranges ("green" or "near infrared" FAF imaging), widefield imaging for visualisation of peripheral retinal areas and quantitative FAF imaging. PMID- 26280649 TI - Sensitive Detection of ssDNA Using an LRET-Based Upconverting Nanohybrid Material. AB - Water-dispersible, optical hybrid nanoparticles are preferred materials for DNA biosensing due to their biocompatibility. Upconverting nanoparticles are highly desirable optical probes in sensors and bioimaging owing to their sharp emission intensity in the visible region. We herein report a highly sensitive ss-DNA detection based on an energy transfer system that uses a nanohybrid material synthesized by doping NaYF4:Tm(3+)/Yb(3+) upconverting nanoparticles (UCNPs) on silica coated polystyrene-co-acrylic acid (PSA) nanoparticles (PSA/SiO2) as the donor, and gold nanoparticles (AuNPs) decorated with Ir(III) complex as the acceptor. UCNPs tagged on PSA/SiO2 and the cyclometalated Ir(III)/AuNP conjugates were then linked through the ss-DNA sequence. Sequential addition of the target DNA to the probe molecular beacon complex resulted in the separation of the optical nanohybrid material and the quencher, leading to a measurable increase in the blue fluorescence emission intensity. Our results have shown a linear relationship between the fluorescence intensity and target DNA concentration down to the picomolar. PMID- 26280650 TI - Visuo-vestibular information processing by unipolar brush cells in the rabbit flocculus. AB - The unipolar brush cell (UBC) is a glutamatergic granular layer interneuron that is predominantly located in the vestibulocerebellum and parts of the vermis. In rat and rabbit, we previously found using juxtacellular labeling combined with spontaneous activity recording that cells with highly regular spontaneous activity belong to the UBC category. Making use of this signature, we recorded from floccular UBCs in both anesthetized and awake rabbits while delivering visuo vestibular stimulation by using sigmoidal rotation of the whole animal. In the anesthetized rabbit, the activity of the presumed UBC units displayed a wide variety of modulation profiles that could be related to aspects of head velocity or acceleration. These modulation profiles could also be found in the awake rabbit where, in addition, they could also carry an eye position signal. Furthermore, units in the awake rabbit could demonstrate rather long response latencies of up to 0.5 s. We suggest that the UBCs recorded in this study mostly belong to the type I UBC category (calretinin-positive) and that they can play diverse roles in floccular visuo-vestibular information processing, such as transformation of velocity-related signals to acceleration-related signals. PMID- 26280651 TI - Microvascular responses to (hyper-)gravitational stress by short-arm human centrifuge: arteriolar vasoconstriction and venous pooling. AB - PURPOSE: We hypothesized that lower body microvessels are particularly challenged during exposure to gravity and hypergravity leading to failure of resistance vessels to withstand excessive transmural pressure during hypergravitation and gravitation-dependent microvascular blood pooling. METHODS: Using a short-arm human centrifuge (SAHC), 12 subjects were exposed to +1Gz, +2Gz and +1Gz, all at foot level, for 4 min each. Laser Doppler imaging and near-infrared spectroscopy were used to measure skin perfusion and tissue haemoglobin concentrations, respectively. RESULTS: Pretibial skin perfusion decreased by 19% during +1Gz and remained at this level during +2Gz. In the dilated area, skin perfusion increased by 24 and 35% during +1Gz and +2Gz, respectively. In the upper arm, oxygenated haemoglobin (Hb) decreased, while deoxy Hb increased with little change in total Hb. In the calf muscle, O2Hb and deoxy Hb increased, resulting in total Hb increase by 7.5 +/- 1.4 and 26.6 +/- 2.6 umol/L at +1Gz and +2Gz, respectively. The dynamics of Hb increase suggests a fast and a slow component. CONCLUSION: Despite transmural pressures well beyond the upper myogenic control limit, intact lower body resistance vessels withstand these pressures up to +2Gz, suggesting that myogenic control may contribute only little to increased vascular resistance. The fast component of increasing total Hb indicates microvascular blood pooling contributing to soft tissue capacitance. Future research will have to address possible alterations of these acute adaptations to gravity after deconditioning by exposure to micro-g. PMID- 26280652 TI - Early resistance training-induced increases in muscle cross-sectional area are concomitant with edema-induced muscle swelling. AB - PURPOSE: It has been proposed that skeletal muscle shows signs of resistance training (RT)-induced muscle hypertrophy much earlier (i.e., ~3-4 weeks of RT) than previously thought. We determined if early increases in whole muscle cross sectional area (CSA) during a period of RT were concomitant with edematous muscle swelling and thus not completely attributable to hypertrophy. METHODS: We analyzed vastus lateralis muscle ultrasound CSA images and their respective echo intensities (CSA-USecho) at the beginning (T1), in the 3rd week of RT (T2) and at the end (T3) of a 10-week RT period in ten untrained young men. Functional parameters [training volume (TV = load * reps * sets) and maximal voluntary contraction (MVC)] and muscle damage markers (myoglobin and interleukin-6) were also assessed. RESULT: Muscle CSA increased significantly at T2 (~2.7%) and T3 (~10.4%) versus T1. Similarly, CSA-USecho increased at T2 (~17.2%) and T3 (~13.7%). However, when CSA-USecho was normalized to the increase in muscle CSA, only T2 showed a significantly higher USecho versus T1. Additionally, TV increased at T2 and T3 versus T1, but MVC increased only at T3. Myoglobin and Interleukin-6 were elevated at T2 versus T1, and myoglobin was also higher at T2 versus T3. CONCLUSION: We propose that early RT-induced increases in muscle CSA in untrained young individuals are not purely hypertrophy, since there is concomitant edema-induced muscle swelling, probably due to muscle damage, which may account for a large proportion of the increase. Therefore, muscle CSA increases (particularly early in an RT program) should not be labeled as hypertrophy without some concomitant measure of muscle edema/damage. PMID- 26280654 TI - Urothelial cells undergo epithelial-to-mesenchymal transition after exposure to muscle invasive bladder cancer exosomes. AB - Bladder cancer, the fourth most common noncutaneous malignancy in the United States, is characterized by high recurrence rate, with a subset of these cancers progressing to a deadly muscle invasive form of disease. Exosomes are small secreted vesicles that contain proteins, mRNA and miRNA, thus potentially modulating signaling pathways in recipient cells. Epithelial-to-mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell-cell adhesion and gain migratory and invasive properties to become mesenchymal stem cells. EMT has been implicated in the initiation of metastasis for cancer progression. We investigated the ability of bladder cancer-shed exosomes to induce EMT in urothelial cells. Exosomes were isolated by ultracentrifugation from T24 or UMUC3 invasive bladder cancer cell conditioned media or from patient urine or bladder barbotage samples. Exosomes were then added to the urothelial cells and EMT was assessed. Urothelial cells treated with bladder cancer exosomes showed an increased expression in several mesenchymal markers, including alpha-smooth muscle actin, S100A4 and snail, as compared with phosphate-buffered saline (PBS)-treated cells. Moreover, treatment of urothelial cells with bladder cancer exosomes resulted in decreased expression of epithelial markers E-cadherin and beta-catenin, as compared with the control, PBS-treated cells. Bladder cancer exosomes also increased the migration and invasion of urothelial cells, and this was blocked by heparin pretreatment. We further showed that exosomes isolated from patient urine and bladder barbotage samples were able to induce the expression of several mesenchymal markers in recipient urothelial cells. In conclusion, the research presented here represents both a new insight into the role of exosomes in transition of bladder cancer into invasive disease, as well as an introduction to a new platform for exosome research in urothelial cells. PMID- 26280655 TI - ST-Segment Elevation Interpretation on Electrocardiogram: To Cath or Not to Cath? PMID- 26280653 TI - How the effects of aging and stresses of life are integrated in mortality rates: insights for genetic studies of human health and longevity. AB - Increasing proportions of elderly individuals in developed countries combined with substantial increases in related medical expenditures make the improvement of the health of the elderly a high priority today. If the process of aging by individuals is a major cause of age related health declines then postponing aging could be an efficient strategy for improving the health of the elderly. Implementing this strategy requires a better understanding of genetic and non genetic connections among aging, health, and longevity. We review progress and problems in research areas whose development may contribute to analyses of such connections. These include genetic studies of human aging and longevity, the heterogeneity of populations with respect to their susceptibility to disease and death, forces that shape age patterns of human mortality, secular trends in mortality decline, and integrative mortality modeling using longitudinal data. The dynamic involvement of genetic factors in (i) morbidity/mortality risks, (ii) responses to stresses of life, (iii) multi-morbidities of many elderly individuals, (iv) trade-offs for diseases, (v) genetic heterogeneity, and (vi) other relevant aging-related health declines, underscores the need for a comprehensive, integrated approach to analyze the genetic connections for all of the above aspects of aging-related changes. The dynamic relationships among aging, health, and longevity traits would be better understood if one linked several research fields within one conceptual framework that allowed for efficient analyses of available longitudinal data using the wealth of available knowledge about aging, health, and longevity already accumulated in the research field. PMID- 26280657 TI - Automatic quantification of mitochondrial fragmentation from two-photon microscope images of mouse brain tissue. AB - The morphology of mitochondria can inform about their functional state and, thus, about cell vitality. For example, fragmentation of the mitochondrial network is associated with many diseases. Recent advances in neuronal imaging have enabled the observation of mitochondria in live brains for long periods of time, enabling the study of their dynamics in animal models of diseases. To aid these studies, we developed an automatic method, based on supervised learning, for quantifying the degree of mitochondrial fragmentation in tissue images acquired via two photon microscopy from transgenic mice, which exclusively express Enhanced cyan fluorescent protein (ECFP) under Thy1 promoter, targeted to the mitochondrial matrix in subpopulations of neurons. We tested the method on images prior to and after cardiac arrest, and found it to be sensitive to significant changes in mitochondrial morphology because of the arrest. We conclude that the method is useful in detecting morphological abnormalities in mitochondria and, likely, in other subcellular structures as well. PMID- 26280658 TI - Erythrocyte Shrinkage and Cell Membrane Scrambling after Exposure to the Ionophore Nonactin. AB - The ionophore antibiotic nonactin permeabilizes cell membranes to NH4+ and K(+) . Treatment of erythrocytes with nonactin is expected to trigger cellular K(+) loss with subsequent cell shrinkage, which in turn is known to trigger suicidal death of a wide variety of cells including erythrocytes. This study explored whether nonactin exposure induces eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and translocation of cell membrane phosphatidylserine to the erythrocyte surface. Signalling of eryptosis includes increase in cytosolic Ca(2+) activity [(Ca(2+) )i ] and stimulation of protein kinase C (PKC) as well as p38 mitogen-activated protein kinase. Phosphatidylserine abundance at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter (FSC) and (Ca(2+) )i from Fluo3-fluorescence. A 48-hr treatment of human erythrocytes with nonactin significantly decreased FSC (>=10 ng/ml) and significantly increased the percentage of annexin-V-binding cells (>=10 ng/ml), effects paralleled by increase in (Ca(2+) )i (>=50 ng/ml) and virtually abrogated by increase in extracellular K(+) concentration to 120 mM at the expense of Na(+) . The up-regulation of annexin-V-binding after nonactin treatment was significantly blunted but not abolished by the removal of extracellular Ca(2+) and by addition of either PKC inhibitor staurosporine (0.4 MUM) or p38 kinase inhibitor SB203580 (2 MUM). In conclusion, exposure of erythrocytes to the K(+) ionophore nonactin induces erythrocyte shrinkage and subsequent erythrocyte membrane scrambling, effects involving cellular K(+) loss, Ca(2+) entry and activation of staurosporine as well as SB203580-sensitive kinases. PMID- 26280656 TI - LAPTM4B facilitates late endosomal ceramide export to control cell death pathways. AB - Lysosome-associated protein transmembrane-4b (LAPTM4B) associates with poor prognosis in several cancers, but its physiological function is not well understood. Here we use novel ceramide probes to provide evidence that LAPTM4B interacts with ceramide and facilitates its removal from late endosomal organelles (LEs). This lowers LE ceramide in parallel with and independent of acid ceramidase-dependent catabolism. In LAPTM4B-silenced cells, LE sphingolipid accumulation is accompanied by lysosomal membrane destabilization. However, these cells resist ceramide-driven caspase-3 activation and apoptosis induced by chemotherapeutic agents or gene silencing. Conversely, LAPTM4B overexpression reduces LE ceramide and stabilizes lysosomes but sensitizes to drug-induced caspase-3 activation. Together, these data uncover a cellular ceramide export route from LEs and identify LAPTM4B as its regulator. By compartmentalizing ceramide, LAPTM4B controls key sphingolipid-mediated cell death mechanisms and emerges as a candidate for sphingolipid-targeting cancer therapies. PMID- 26280660 TI - Composite Films of Poly(vinyl alcohol) and Bifunctional Cross-linking Cellulose Nanocrystals. AB - Long and flexible cellulose nanofibrils or stiff and short cellulose nanocrystals (CNCs) are both promising lightweight materials with high strength and the potential to serve as reinforcing agents in many polymeric materials. In this study, bifunctional reactive cellulose nanocrystals (RCNCs) with carboxyl and aldehyde functionalities were used as reinforcements to prepare acetal-bonding cross-linked poly(vinyl alcohol) (PVA) films. Two RCNCs were obtained through the mechanical homogenization of partially carboxylated dialdehyde cellulose (DAC) with a residual aldehyde content of 0.55 and 1.93 mmol/g and a carboxyl content of 1.65 and 1.93 mmol/g, respectively. The mechanical, thermal, and barrier properties of PVA-RCNC films with a variable mass ratio of RCNCs (0.5-10%) were determined. Reference CNCs without reactive aldehydes were obtained through the reduction of aldehyde functionalities to primary hydroxide groups, and their reinforcing effect was compared to RCNCs. With the addition of 10% acetal-bonding RCNCs with respect to PVA weight, the tensile strength and Young's modulus were up to 2-fold greater than those of pure PVA film. An addition of only 0.5% RCNCs improved the tensile strength of the PVA film by 66% and the modulus by 61%. In comparison, a significantly lower reinforcing effect (19% with CNC loading of 0.5%) was found using reference CNCs. PVA's effective oxygen barrier and thermal properties were preserved when RCNCs were introduced into the films. PMID- 26280659 TI - The imagined itch: brain circuitry supporting nocebo-induced itch in atopic dermatitis patients. AB - BACKGROUND: Psychological factors are known to significantly modulate itch in patients suffering from chronic itch. Itch is also highly susceptible to both placebo and nocebo (negative placebo) effects. Brain activity likely supports nocebo-induced itch, but is currently unknown. METHODS: We collected functional MRI (fMRI) data from atopic dermatitis (AD) patients, in a within-subject design, and contrast brain response to nocebo saline understood to be allergen vs open label saline control. Exploratory analyses compared results to real allergen itch response and placebo responsiveness, evaluated in the same patients. RESULTS: Nocebo saline produced greater itch than open saline control (P < 0.01). Compared to open saline, nocebo saline demonstrated greater fMRI response in caudate, dorsolateral prefrontal cortex (dlPFC), and intraparietal sulcus (iPS) - brain regions important for cognitive executive and motivational processing. Exploratory analyses found that subjects with greater dlPFC and caudate activation to nocebo-induced itch also demonstrated greater dlPFC and caudate activation, respectively, for real allergen itch. Subjects reporting greater nocebo-induced itch also demonstrated greater placebo reduction of allergen evoked itch, suggesting increased generalized modulation of itch perception. CONCLUSIONS: Our study demonstrates the capacity of nocebo saline to mimic both the sensory and neural effects of real allergens and provides an insight to the brain mechanisms supporting nocebo-induced itch in AD, thus aiding our understanding of the role that expectations and other psychological factors play in modulating itch perception in chronic itch patients. PMID- 26280661 TI - Maxillary canine-first premolar bilateral transposition in a Class III patient: A case report. AB - Tooth transposition is a rare dental anomaly that often represents a challenge for the clinician. The case of a girl with skeletal Class III malocclusion and concomitant maxillary canine-first premolar bilateral transposition, followed from 7 to 17 years of age, is presented. After a first phase of treatment aimed at resolving the Class III malocclusion, the transposition was maintained and the case finalized with a multibracket appliance. PMID- 26280662 TI - A randomized controlled trial evaluating antioxidant-essential oil gel as a treatment for gingivitis in orthodontic patients. AB - OBJECTIVE: To evaluate the treatment effect of an antioxidant-essential oil gel on orthodontic patients with generalized gingivitis. The gel contains the essential oils menthol and thymol and the antioxidants ferulic acid and phloretin. MATERIALS AND METHODS: Thirty patients from the university's orthodontic clinic were screened for gingivitis and randomly allocated into treatment and placebo-control groups. Each patient was evaluated at three orthodontic treatment visits (T1, T2, and T3). A periodontal examination, including probing depth (PD), bleeding on probing (BOP), gingival index (GI), and plaque index (PI) was performed at each visit. Between T1 and T2, patients were instructed to apply a topical gel (active or placebo) to their gingiva twice daily after brushing. From T2 to T3, patients were instructed to discontinue use of the gel. RESULTS: The treatment group showed statistically significant (P < .05) reductions of BOP (-13.6 percentage points) and GI (-0.14) between T1 and T2, and significant increases in BOP (13.3 percentage points) and GI (0.14) between T2 and T3. Except for an increase in the GI between T2 and T3, the control group showed no significant changes in BOP or GI over time. The only other significant changes that occurred pertained to the treatment group, which showed significant increases in PD (0.08 mm) and PI (0.18) between T2 and T3. CONCLUSION: Application of a topical antioxidant-essential oil gel is an effective means of reducing inflammation in orthodontic patients with gingivitis. PMID- 26280667 TI - Electrochemistry at a Metal Nanoparticle on a Tunneling Film: A Steady-State Model of Current Densities at a Tunneling Ultramicroelectrode. AB - Here, a new methodology is proposed for treating electrochemical current densities in metal-insulator-metal nanoparticle (M-I-MNP) systems. The described model provides broad, practical insights about MNP-mediated electron transfer to redox species in solution, where electron transfer from the underlying electrode to a MNP via tunneling and heterogeneous electron transfer from the MNP to redox species in solution are treated as sequential steps. Tunneling is treated through an adaptation of the Simmons model of tunneling in metal-insulator-metal structures, and explicit equations are provided for tunneling currents, which demonstrate the effect of various experimental parameters, such as insulator thickness and MNP size. Overall, a general approach is demonstrated for determining experimental conditions where tunneling will have a measurable impact on the electrochemistry of M-I-MNP systems. PMID- 26280666 TI - The Sexual Acceptability of Intrauterine Contraception: A Qualitative Study of Young Adult Women. AB - CONTEXT: The IUD is extremely effective but infrequently used by young adult women, who disproportionately experience unintended pregnancies. Research has not examined how IUD use may affect sexuality, which could in turn affect method acceptability, continuation and marketing efforts. METHODS: Focus group discussions and interviews were conducted in 2014 with 50 women between the ages of 18 and 29-either University of Wisconsin students or women from the surrounding community who received public assistance-to explore their thoughts about whether and how IUD use can affect sexual experiences. A modified grounded theory approach was used to identify common themes in terms of both experienced and anticipated sexual acceptability of the IUD. RESULTS: Six themes emerged: security (IUD's efficacy can reduce sexual inhibition), spontaneity (IUD can allow for free-flowing sex), sexual aspects of bleeding and cramping (IUD's side effects can affect sex), scarcity of hormones (IUD has a low level of or no hormones, and reduces libido less than hormonal methods, such as the pill), string (IUD's string can detract from a partner's sexual experience) and stasis (IUD use can have no impact on sex). Some reported sexual aspects of IUD use were negative, but most were positive and described ever-users' method satisfaction and never-users' openness to use the method. DISCUSSION: Future research and interventions should attend to issues of sexual acceptability: Positive sexual aspects of the IUD could be used promotionally, and counseling about sexual concerns could increase women's willingness to try the method. PMID- 26280668 TI - Hepatitis B: 50 years after the discovery of Australia antigen. AB - It is an honour to be invited to recount the progress in our understanding and management of hepatitis B 50 years after the discovery of Australia antigen (Au Ag). During this half century, we have gone from identifying the causative agent- hepatitis B virus (HBV), understanding its biology and the disease it causes, to having vaccines that can prevent HBV infection and antiviral therapy that can suppress HBV replication and prevent progression of HBV-related liver disease. As a result of the progress, prevalence of HBV infection and morbidity and mortality from chronic HBV infection has declined. PMID- 26280669 TI - A Clinical Algorithm to Identify HIV Patients at High Risk for Incident Active Tuberculosis: A Prospective 5-Year Cohort Study. AB - BACKGROUND: Predicting the risk of tuberculosis (TB) in people living with HIV (PLHIV) using a single test is currently not possible. We aimed to develop and validate a clinical algorithm, using baseline CD4 cell counts, HIV viral load (pVL), and interferon-gamma release assay (IGRA), to identify PLHIV who are at high risk for incident active TB in low-to-moderate TB burden settings where highly active antiretroviral therapy (HAART) is routinely provided. MATERIALS AND METHODS: A prospective, 5-year, cohort study of adult PLHIV was conducted from 2006 to 2012 in two hospitals in Taiwan. HAART was initiated based on contemporary guidelines (CD4 count < = 350/MUL). Cox regression was used to identify the predictors of active TB and to construct the algorithm. The validation cohorts included 1455 HIV-infected individuals from previous published studies. Area under the receiver operating characteristic (ROC) curve was calculated. RESULTS: Seventeen of 772 participants developed active TB during a median follow-up period of 5.21 years. Baseline CD4 < 350/MUL or pVL >= 100,000/mL was a predictor of active TB (adjusted HR 4.87, 95% CI 1.49-15.90, P = 0.009). A positive baseline IGRA predicted TB in patients with baseline CD4 >= 350/MUL and pVL < 100,000/mL (adjusted HR 6.09, 95% CI 1.52-24.40, P = 0.01). Compared with an IGRA-alone strategy, the algorithm improved the sensitivity from 37.5% to 76.5%, the negative predictive value from 98.5% to 99.2%. Compared with an untargeted strategy, the algorithm spared 468 (60.6%) from unnecessary TB preventive treatment. Area under the ROC curve was 0.692 (95% CI: 0.587-0.798) for the study cohort and 0.792 (95% CI: 0.776-0.808) and 0.766 in the 2 validation cohorts. CONCLUSIONS: A validated algorithm incorporating the baseline CD4 cell count, HIV viral load, and IGRA status can be used to guide targeted TB preventive treatment in PLHIV in low-to-moderate TB burden settings where HAART is routinely provided to all PLHIV. The implementation of this algorithm will avoid unnecessary exposure of low-risk patients to drug toxicity and simultaneously, reduce the burden of universal treatment on the healthcare system. PMID- 26280670 TI - Astaxanthin Normalizes Epigenetic Modifications of Bovine Somatic Cell Cloned Embryos and Decreases the Generation of Lipid Peroxidation. AB - Astaxanthin is an extremely common antioxidant scavenging reactive oxygen species (ROS) and blocking lipid peroxidation. This study was conducted to investigate the effects of astaxanthin supplementation on oocyte maturation, and development of bovine somatic cell nuclear transfer (SCNT) embryos. Cumulus-oocyte complexes were cultured in maturation medium with astaxanthin (0, 0.5, 1.0, or 1.5 mg/l), respectively. We found that 0.5 mg/l astaxanthin supplementation significantly increased the proportion of oocyte maturation. Oocytes cultured in 0.5 mg/l astaxanthin supplementation were used to construct SCNT embryos and further cultured with 0, 0.5, 1.0 or 1.5 mg/l astaxanthin. The results showed that the supplementation of 0.5 mg/l astaxanthin significantly improved the proportions of cleavage and blastulation, as well as the total cell number in blastocysts compared with the control group, yet this influence was not concentration dependent. Chromosomal analyses revealed that more blastomeres showed a normal chromosomal complement in 0.5 mg/l astaxanthin treatment group, which was similar to that in IVF embryos. The methylation levels located on the exon 1 of the imprinted gene H19 and IGF2, pluripotent gene OCT4 were normalized, and global DNA methylation, H3K9 and H4K12 acetylation were also improved significantly, which was comparable to that in vitro fertilization (IVF) embryos. Moreover, we also found that astaxanthin supplementation significantly decreased the level of lipid peroxidation. Our findings showed that the supplementation of 0.5 mg/l astaxanthin to oocyte maturation medium and embryo culture medium improved oocyte maturation, SCNT embryo development, increased chromosomal stability and normalized the epigenetic modifications, as well as inhibited overproduction of lipid peroxidation. PMID- 26280672 TI - A Developmental Analysis of Caregiving Modalities Across Infancy in 38 Low- and Middle-Income Countries. AB - Caregiving is requisite to wholesome child development from the beginning of life. A cross-sectional microgenetic analysis of six caregiving practices across the child's 1st year (0-12 months) in 42,539 families from nationally representative samples in 38 low- and middle-income countries is reported. Rates of caregiving varied tremendously within and across countries. However, caregiving practices followed one of two developmental trajectories: (a) greater proportions of caregivers read, told stories, and named, counted, and drew with each additional month of infant age, and (b) proportions of caregivers who played, sang songs, and took their infants outside increased each month from birth but reached an asymptote at 4-5 months. Rates and growth functions of caregiving have implications for infant care and development. PMID- 26280673 TI - Vitamin D Induces Cyclooxygenase 2 Dependent Prostaglandin E2 Synthesis in HaCaT Keratinocytes. AB - The active metabolite of vitamin D calcitriol and its analogs are well-known for their anti-inflammatory action in the skin, while their main side effect associated with topical treatment of inflammatory disorders is irritant contact dermatitis. Prostaglandin E2 (PGE2 ) is pro-inflammatory at the onset of inflammation and anti-inflammatory at its resolution. We hypothesized that induction of PGE2 synthesis by calcitriol in epidermal keratinocytes may contribute both to its pro-inflammatory and anti-inflammatory effects on the skin. Treatment of human immortalized HaCaT keratinocytes with calcitriol (3-100 nM, 2-24 h) increased PGE2 production due to increased mRNA and protein expression of COX-2, but not to increase of COX-1 or release of arachidonic acid. The effect of calcitriol on COX-2 mRNA was observed also in primary human keratinocytes. The increase in COX-2 mRNA is associated with COX-2 transcript stabilization. Calcitriol exerts this effect by a rapid (2 h) and protein synthesis independent mode of action that is dependent on PKC and Src kinase activities. Treatment with a COX-2 inhibitor partially prevented the attenuation of the keratinocyte inflammatory response by calcitriol. We conclude that upregulation of COX-2 expression with the consequent increase in PGE2 synthesis may be one of the mechanisms explaining the Janus face of calcitriol as both a promoter and attenuator of cutaneous inflammation. J. Cell. Physiol. 231: 837 843, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26280674 TI - Caprylic acid-induced impurity precipitation from protein A capture column elution pool to enable a two-chromatography-step process for monoclonal antibody purification. AB - This article presents the use of caprylic acid (CA) to precipitate impurities from the protein A capture column elution pool for the purification of monoclonal antibodies (mAbs) with the objective of developing a two chromatography step antibody purification process. A CA-induced impurity precipitation in the protein A column elution pool was evaluated as an alternative method to polishing chromatography techniques for use in the purification of mAbs. Parameters including pH, CA concentrations, mixing time, mAb concentrations, buffer systems, and incubation temperatures were evaluated on their impacts on the impurity removal, high-molecular weight (HMW) formation and precipitation step yield. Both pH and CA concentration, but not mAb concentrations and buffer systems, are key parameters that can affect host-cell proteins (HCPs) clearance, HMW species, and yield. CA precipitation removes HCPs and some HMW species to the acceptable levels under the optimal conditions. The CA precipitation process is robust at 15 25 degrees C. For all five mAbs tested in this study, the optimal CA concentration range is 0.5-1.0%, while the pH range is from 5.0 to 6.0. A purification process using two chromatography steps (protein A capture column and ion exchange polishing column) in combination with CA-based impurity precipitation step can be used as a robust downstream process for mAb molecules with a broad range of isoelectric points. Residual CA can be effectively removed by the subsequent polishing cation exchange chromatography. PMID- 26280676 TI - Breaking a bottleneck: Accurate extrapolation to "gold standard" CCSD(T) energies for large open shell organic radicals at reduced computational cost. AB - Open Shell organic radicals are principal species involved in many diverse areas such as combustion, photochemistry, and polymer chemistry. Computational studies of such species with an accurate method like coupled-cluster with single and double and perturbative triple (CCSD(T)) may be restricted to systems of modest size due to the steep computational scaling of the method. Herein, we assess the accuracy of extrapolated CCSD(T) energies determined using the connectivity-based hierarchy (CBH) method on medium to large sized radicals. In our method, an MP2 calculation on the target radical is coupled with CCSD(T) energies of fragments determined uniquely by our hierarchy to perform accurate extrapolations. A careful assessment is done with a robust CBH-rad49 test set comprising of 49 diverse cyclic and acyclic radicals with a variety of functional groups. We demonstrate that the extrapolation method with CBH-2 or CBH-3 is sufficient to obtain sub-kcal accuracy. ROMP2 and PMP2 calculations with both Pople-style and Dunning-style basis-sets resulted in mean absolute errors for CCSD(T) extrapolation (full CCSD(T)-extrapolated CCSD(T)) within 0.5 kcal/mol. Further speedup for such CCSD(T) extrapolations are obtained with ROHF-based RI-MP2 calculations. Challenging systems with (a) high ring strain, (b) delocalized character, and (c) spin contamination are identified and analyzed in detail. Finally, we apply our extrapolation method on 10 larger radicals containing 10-15 heavy atoms, where accurate CCSD(T) energies are obtained at a fractional cost of full CCSD(T) calculations. PMID- 26280671 TI - Chinese Systemic Lupus Erythematosus Treatment and Research Group Registry VI: Effect of Cigarette Smoking on the Clinical Phenotype of Chinese Patients with Systemic Lupus Erythematosus. AB - OBJECTIVES: Our study aimed to investigate the effect of cigarette smoking on the clinical phenotype of patients registered in the Chinese Systemic Lupus Erythematosus (SLE) Treatment and Research (CSTAR) group registry database, the first online registry of Chinese patients with SLE. METHODS: A prospective cross sectional study of Chinese SLE patients was conducted using the CSTAR. Our case control analysis was performed on age- and gender-matched subjects to explore the potential effect of cigarette smoking on the clinical manifestation of SLE. RESULTS: Smokers comprised 8.9% (65/730) of patients, and the ratio of females/males was 19/46. Thirty-nine patients were current smokers, and 26 were ex-smokers. Data showed significant differences between smokers and nonsmokers in the following areas: nephropathy (58.5% vs. 39.2%; p = 0.003), microscopic hematuria (30.8% vs. 19.1%; p = 0.025), proteinuria (53.8% vs. 34.4%; p = 0.002), and SLE Disease Activity Index(DAI) scores (12.38+/-8.95 vs. 9.83+/-6.81; p = 0.028). After adjusting for age and gender, significant differences between smokers and nonsmokers were found with photosensitivity (35.9% vs. 18%; p = 0.006), nephropathy (59.4% vs. 39.8%; p = 0.011), and proteinuria (54.7% vs. 35.2%). Although smokers tended to have greater disease severity compared with nonsmokers (SLEDAI scores: 12.58+/-8.89 vs.10.5+/-7.09), the difference was not significant (p = 0.081). CONCLUSIONS: Cigarette smoking triggers the development and exacerbation of SLE, especially with respect to renal involvement. Chinese smokers with SLE should be advised to discontinue cigarette use. PMID- 26280675 TI - Estimating the Effect of Influenza Vaccination on Nursing Home Residents' Morbidity and Mortality. AB - OBJECTIVES: To estimate the effect of influenza vaccination on hospitalization and mortality in nursing home (NH) residents. DESIGN: Retrospective cohort study. SETTING: Medicare claims data linked to NH Minimum Data Set assessments and Centers for Disease Control and Prevention (CDC) surveillance data from 122 U.S. cities. PARTICIPANTS: More than 1 million Medicare fee-for-service, long-stay NH residents between 2000 and 2009. MEASUREMENTS: Weekly facility outcome aggregates of NH resident pneumonia and influenza (P&I) hospitalizations and all-cause mortality and city-level P&I mortality as reported by the CDC were created. The seasonal vaccine match rate for influenza A/H1N1, A/H3N2, and B strains was calculated, and each outcome was compared in seasons of high and low match rates using facility fixed-effects regression models separately for full-year and nonsummer months. RESULTS: Average weekly all-cause mortality varied across seasons from 3.74 to 4.13 per 1,000 NH residents per week, and hospitalization for P&I varied from 2.05 to 2.43. Vaccine match rates were invariably high for H1N1 but variable across seasons for the other two types. The association between vaccine match and reduction in overall mortality and P&I hospitalizations was strongest for A/H3N2, the influenza strain typically responsible for the most severe influenza cases. Given the approximately 130,000 deaths and 77,000 P&I hospitalizations of long-stay NH residents during the 32 nonsummer weeks, the model estimated that a 50-percentage-point increase in the A/H3N2 match rate (from <25% to >75%) reduced long-stay NH resident deaths by 2.0% and P&I hospitalizations by 4.2%. CONCLUSION: Well-matched influenza vaccine prevents P&I hospitalizations and mortality in NH residents. PMID- 26280678 TI - Construct Validation of Three Nutrition Questions Using Health and Diet Ratings in Older Canadian Males Living in the Community. AB - Brief nutrition screening tools are desired for research and practice. Seniors in the Community: Risk Evaluation for Eating and Nutrition (SCREEN-II, 14 items) and the abbreviated version SCREEN-II-AB (8 items) are valid and reliable nutrition screening tools for older adults. This exploratory study used a retrospective cross-sectional design to determine the construct validity of a subset of 3 items (weight loss, appetite, and swallowing difficulty) currently on the SCREEN-II and SCREEN-II-AB tools. Secondary data on community-dwelling senior males (n = 522, mean +/- SD age = 86.7 +/- 3.0 years) in the Manitoba Follow-up Study (MFUS) study were available for analysis. Participants completed the mailed MFUS Nutrition Survey that included SCREEN-II items and questions pertaining to self rated health, diet healthiness, and rating of the importance of nutrition towards successful aging as the constructs for comparison. Self-perceived health status (F = 14.7, P < 0.001), diet healthiness (rho = 0.17, P = 0.002) and the rating of nutrition's importance to aging (rho = 0.10, P = 0.03) were correlated with the 3 item score. Inferences were consistent with associations between these construct variables and the full SCREEN-II. Three items from SCREEN-II and SCREEN-II-AB demonstrate initial construct validity with self-perceived health status and diet healthiness ratings by older males; further exploration for criterion and predictive validity in more diverse samples is needed. PMID- 26280677 TI - Expression and Characterization of Recombinant, Tetrameric and Enzymatically Active Influenza Neuraminidase for the Setup of an Enzyme-Linked Lectin-Based Assay. AB - Developing a universal influenza vaccine that induces broad spectrum and longer term immunity has become an important potentially achievable target in influenza vaccine research and development. Hemagglutinin (HA) and neuraminidase (NA) are the two major influenza virus antigens. Although antibody responses against influenza virus are mainly directed toward HA, NA is reported to be more genetically stable; hence NA-based vaccines have the potential to be effective for longer time periods. NA-specific immunity has been shown to limit the spread of influenza virus, thus reducing disease symptoms and providing cross-protection against heterosubtypic viruses in mouse challenge experiments. The production of large quantities of highly pure and stable NA could be beneficial for the development of new antivirals, subunit-based vaccines, and novel diagnostic tools. In this study, recombinant NA (rNA) was produced in mammalian cells at high levels from both swine A/California/07/2009 (H1N1) and avian A/turkey/Turkey/01/2005 (H5N1) influenza viruses. Biochemical, structural, and immunological characterizations revealed that the soluble rNAs produced are tetrameric, enzymatically active and immunogenic, and finally they represent good alternatives to conventionally used sources of NA in the Enzyme-Linked Lectin Assay (ELLA). PMID- 26280679 TI - High incidence of germline BRCA mutation in patients with ER low-positive/PR low positive/HER-2 neu negative tumors. AB - BACKGROUND: The 2015 National Comprehensive Cancer Network guidelines recommend that genetic counseling and germline BRCA mutation testing be offered to women under age 60 with triple-negative breast cancer (TNBC). As a result of the 2010 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for breast cancer, patients with breast cancers that are estrogen receptor (ER) or progesterone receptor (PR) low-positive (1%-9% on immunohistochemistry) are no longer strictly considered to have TNBC and may not be referred for genetic counseling. However, the incidence of BRCA mutation in patients with hormone receptor (HR) low-positive breast cancers remains unknown, and current ASCO/CAP guidelines may result in undertesting for BRCA mutations. METHODS: A prospectively maintained research database of breast cancer patients evaluated at The University of Texas MD Anderson Cancer Center between 2004 and 2014 was reviewed; 314 patients were identified with HER2/neu-negative breast cancers expressing ER and PR <10% with known BRCA mutation status. RESULTS: Three hundred fourteen patients had breast cancers expressing ER and PR <10%; 238 (75.8%) had HR-negative cancers (<1% ER and PR), and 76 (24.2%) had HR-low positive cancers (1%-9% ER and/or PR). Among patients with HR-negative tumors, 86 of 238 (36.1%) had a BRCA1/2 mutation, whereas in the HR-low-positive group, 30 of 76 (39.5%) had a BRCA1/2 mutation. In multivariate analysis, HR status (<1% vs 1%-9%) was not significantly associated with BRCA1/2 mutations. CONCLUSIONS: The incidence of BRCA1/2 mutations is similar in patients with HR-low-positive breast cancer and patients with HR-negative breast cancer. Genetic counseling and BRCA testing should be offered to patients under age 60 who have HR-low-positive breast cancers. Cancer 2015;121:3435-43. (c) 2015 American Cancer Society. PMID- 26280680 TI - Effects of aging on cardiac extracellular matrix in men and women. AB - PURPOSE: Aging has severe implications for tissue damage and is a major risk factor for disease. However, the effects of aging on cardiac extracellular matrix (ECM) components in individuals free of cardiovascular disease are incompletely understood. We aimed at the characterization of the effects of aging on major ECM proteins in the heart of men and women. EXPERIMENTAL DESIGN: Left ventricular (LV) samples of nondiseased human hearts technically unusable for transplantation obtained from general organ donors (n = 31; age 17-68 years; 48% women) were used for protein isolation. We separated the group into 17-40 years (n = 7 men and 7 women) and 50-68 years (n = 9 men and 8 women). RESULTS: Analysis of ECM proteins demonstrated an age-dependent sex-specific regulation of collagen type I and III (interaction p < 0.05), type VI (interaction p = 0.01), tissue inhibitor of metalloproteinase 3 (interaction p < 0.05), SMAD2 (interaction p < 0.05), and SMAD3 (interaction p = 0.001). Overall, the levels of these proteins in younger individuals were lower in women than men, while in older individuals they were higher in women than men. CONCLUSIONS AND CLINICAL RELEVANCE: This age-mediated myocardial ECM remodeling might play a key role in the limited ability of the aging heart to adapt adequately to altered work load and to respond to tissue damage. Therapeutic agents that target ECM homeostasis represent promising prevention strategies. PMID- 26280682 TI - Letter to the Editor: Does the Risk Assessment and Prediction Tool Predict Discharge Disposition After Joint Replacement? PMID- 26280681 TI - Treatment of Periprosthetic Knee Infection With a Two-stage Protocol Using Static Spacers. AB - BACKGROUND: Two-stage exchange arthroplasty is a standard approach for treating total knee arthroplasty periprosthetic joint infection in the United States, but whether this should be performed with a static antibiotic spacer or an articulating one that allows range of motion before reimplantation remains controversial. It is unclear if the advantages of articulating spacers (easier surgical exposure during reimplantation and improved postoperative flexion) outweigh the disadvantages of increased cost and complexity in the setting of similar rates of infection eradication. QUESTIONS/PURPOSES: The purposes of this study were (1) to determine the ultimate range of motion; and (2) to determine the proportion of patients who remained free of infection at a minimum 2 years after treatment with static antibiotic spacers as part of a two-stage revision TKA for the treatment of periprosthetic joint infection. METHODS: Between 1999 and 2011, we treated 121 patients with chronically infected TKAs, of whom three had medical comorbidities precluding a two-stage exchange, four had died before 2 year followup for reasons other than the surgical intervention, and seven were lost to followup. The remaining 107 patients (109 knees; 53 men and 54 women) were treated using a two-stage approach with static spacers and are evaluated here at a mean of 3.7 years (range, 2.0-9.8 years); no patients were treated with articulating spacers during this study period. Twenty-five percent (27 of 109) of the organisms isolated the first-stage procedure were resistant to methicillin and/or vancomycin. Median age at the time of reimplantation was 67 years (range, 42-89 years). Range of motion was measured by an independent physical therapist with a standard goniometer. Knee Society knee and function scores were calculated before the first stage and at the 2-year mark. Because many of these patients were treated before consensus definitions of infection were established, we made the diagnosis of infection (and established that a patient was believed to be free of infection) using the approaches prevalent at that time, which generally included presence of a sinus tract communicating directly with the implant, two positive tissue cultures, or a combination of cultures, fluid analysis, and serology. RESULTS: Postoperatively, 67 knees had full extension and no patients had a flexion contracture > 10 degrees . Median flexion was 100 degrees (range, 60 degrees -139 degrees ). Thirty-nine knees had postoperative flexion > 120 degrees . Ninety-four percent of patients were clinically free of infection at last followup. CONCLUSIONS: Our two-stage exchange protocol with static spacers yielded comparable flexion and infection eradication when compared with other recent studies that have used articulating spacers. The large proportion of resistant organisms is alarming. Future multicenter studies should compare static with articulating spacers and should evaluate both cost and efficacy, because our study suggests that adequate range of motion can be achieved without the added cost of the articulating spacer. LEVEL OF EVIDENCE: Level IV, therapeutic study. PMID- 26280683 TI - CORR Insights((r)): Can an Arthroplasty Registry Help Decrease Transfusions in Primary Total Joint Replacement? A Quality Initiative. PMID- 26280684 TI - Identification of Anaerobic Aniline-Degrading Bacteria at a Contaminated Industrial Site. AB - Anaerobic aniline biodegradation was investigated under different electron accepting conditions using contaminated canal and groundwater aquifer sediments from an industrial site. Aniline loss was observed in nitrate- and sulfate amended microcosms and in microcosms established to promote methanogenic conditions. Lag times of 37 days (sulfate amended) to more than 100 days (methanogenic) were observed prior to activity. Time-series DNA-stable isotope probing (SIP) was used to identify bacteria that incorporated (13)C-labeled aniline in the microcosms established to promote methanogenic conditions. In microcosms from heavily contaminated aquifer sediments, a phylotype with 92.7% sequence similarity to Ignavibacterium album was identified as a dominant aniline degrader as indicated by incorporation of (13)C-aniline into its DNA. In microcosms from contaminated canal sediments, a bacterial phylotype within the family Anaerolineaceae, but without a match to any known genus, demonstrated the assimilation of (13)C-aniline. Acidovorax spp. were also identified as putative aniline degraders in both of these two treatments, indicating that these species were present and active in both the canal and aquifer sediments. There were multiple bacterial phylotypes associated with anaerobic degradation of aniline at this complex industrial site, which suggests that anaerobic transformation of aniline is an important process at the site. Furthermore, the aniline degrading phylotypes identified in the current study are not related to any known aniline degrading bacteria. The identification of novel putative aniline degraders expands current knowledge regarding the potential fate of aniline under anaerobic conditions. PMID- 26280685 TI - Stabilization of Phenolic Radicals on Graphene Oxide: An XPS and EPR Study. AB - A graphene oxide-gallic acid hybrid material was synthesized by the immobilization of gallic acid (3,4,5-trihydroxobenzoic acid) on graphene oxide. The grafting was achieved via the formation of amide bonds between the amine groups on the organofunctionalized graphite oxide surface and the carboxyl groups of the gallic acid molecules. The EPR signal of the gallic acid radicals in this hybrid material remained almost unaltered over at least 500 days, with less than 3% signal decay over that period, pointing to the truly remarkable stability of these radicals. The produced material was characterized by Fourier transform infrared, X-ray photoelectron, and electron paramagnetic resonance spectroscopies as well as by thermogravimetric analysis and the Kaiser test. The stability of the radicals in the material was studied in powder form and in aqueous solution vs pH. We demonstrate that in the graphene oxide-gallic acid hybrid material a radical is favorably stabilized on the ring-O while the oxidation of the second OH is precluded, and this results in long-term stabilization of the gallic acid radicals in solid hybrid material. Thus, in applications where it will be used under O2-free and humidity-free conditions, the graphene oxide-gallic acid hybrid material is a reliable spintronics scaffold. PMID- 26280686 TI - Thermal Conductive and Mechanical Properties of Polymeric Composites Based on Solution-Exfoliated Boron Nitride and Graphene Nanosheets: A Morphology-Promoted Synergistic Effect. AB - In this work, we reported a synergistic effect of boron nitride (BN) with graphene nanosheets on the enhancement of thermal conductive and mechanical properties of polymeric composites. Here, few layered BN (s-BN) and graphene (s GH) were used and obtained by liquid exfoliation method. The polystyrene (PS) and polyamide 6 (PA) composites were obtained via solution blending method and subsequently hot-pressing. The experimental results suggested that the thermal conductivity (TC) of the PS and PA composites increases with additional introduction of s-BN. For example, compared with the composites containing 20 wt % s-GH, additional introduction of only 1.5 wt % s-BN could increase the TC up to 38 and 34% in polystyrene (PS) and polyamide 6 (PA) matrix, respectively. Meanwhile, the mechanical properties of the composites were synchronously enhanced. It was found that s-BN filled in the interspaces of s-GH sheets and formed s-BN/s-GH stacked structure, which were helpful for the synchronously improving TC and mechanical properties of the polymeric materials. PMID- 26280687 TI - Nonlinear optical properties of rhenium(I) complexes: Influence of the extended pi-conjugated connectors and proton abstraction. AB - The photoinduced proton-coupled electron transfer chemistry is very crucial to the development of nonlinear optical (NLO) materials with large first hyperpolarizability contrast. We have performed a systematic investigation on the geometric structures, NLO switching, and simulated absorption spectra of rhenium(I) complexes via density functional theory (DFT). The results show that the first hyperpolarizabilities (betavec) increase remarkably with further extending of the organic connectors. In addition, the solvent leads to a slight enhancement of the hyperpolarizability and frequency dependent hyperpolarizability. Furthermore, the proton abstraction plays an important role in tuning the second-order NLO response. It is found that deprotonation not only increases the absolute value of betavec but also changes the sign of betavec from positive to negative. This different sign can be explained by the opposite dipole moments. The efficient enhancement of first hyperpolarizability is attributed to the better delocalization of the pi-electron system and the more obvious degree of charge transfer. Therefore, these kinds of complexes might be promising candidates for designed as proton driven molecular second-order NLO switching. PMID- 26280688 TI - Identification of novel allosteric modulator binding sites in NMDA receptors: A molecular modeling study. AB - The dysfunction of N-methyl-d-Aspartate receptors (NMDARs), a subtype of glutamate receptors, is correlated with schizophrenia, stroke, and many other neuropathological disorders. However, not all NMDAR subtypes equally contribute towards these disorders. Since NMDARs composed of different GluN2 subunits (GluN2A-D) confer varied physiological properties and have different distributions in the brain, pharmacological agents that target NMDARs with specific GluN2 subunits have significant potential for therapeutic applications. In our previous research, we have identified a family of novel allosteric modulators that differentially potentiate and/or inhibit NMDARs of differing GluN2 subunit composition. To further elucidate their molecular mechanisms, in the present study, we have identified four potential binding sites for novel allosteric modulators by performing molecular modeling, docking, and in silico mutations. The molecular determinants of the modulator binding sites (MBS), analysis of particular MBS electrostatics, and the specific loss or gain of binding after mutations have revealed modulators that have strong potential affinities for specific MBS on given subunits and the role of key amino acids in either promoting or obstructing modulator binding. These findings will help design higher affinity GluN2 subunit-selective pharmaceuticals, which are currently unavailable to treat psychiatric and neurological disorders. PMID- 26280689 TI - A 11.7-Mb Paracentric Inversion in Chromosome 1q Detected in Prenatal Diagnosis Associated with Familial Intellectual Disability. AB - Most apparent balanced chromosomal inversions are usually clinically asymptomatic; however, infertility, miscarriages, and mental retardation have been reported in inversion carriers. We present a small family with a paracentric inversion 1q42.13q43 detected in routine prenatal diagnosis. Molecular cytogenetic methods defined the size of the inversion as 11.7 Mb and excluded other unbalanced chromosomal alterations in the patients. Our findings suggest that intellectual disability is caused by dysfunction, disruption, or position effects of genes located at or near the breakpoints involved in this inversion. PMID- 26280690 TI - The role of exaggerated patellar tendon reflex in knee joint position sense in patients with cerebral palsy. AB - The aim of this pilot study was to determine if exaggerated patellar tendon jerk affects knee joint position sense (JPS) in cerebral palsy (CP) patients, by comparing JPS of the knee between participants with normal and exaggerated reflexes. The thresholds for reflex classification were based upon the data from able-bodied volunteers. JPS was measured as the ability of a subject (with eyes closed) to replicate a knee joint position demonstrated by an examiner. Tendon jerk was measured as the moment of force in response to patellar tendon taps. Data was collected from 27 limbs of CP patients (N=14) and 36 limbs of able bodied volunteers (N=18). JPS was less accurate (p=0.014) in limbs with non exaggerated reflexes (50.28+/-43.63%) than in control limbs (11.84+/-10.85%). There was no significant difference (p=0.08) in JPS accuracy between limbs with exaggerated reflexes (18.66+/-15.50%) and control limbs. Our data suggests that one component of sensorimotor impairment, JPS, is not as commonly affected in CP patients as previously reported. JPS of the knee is reduced in limbs with non exaggerated reflexes; however in limbs with exaggerated reflexes which is seen in the majority of CP patients, JPS is not affected. PMID- 26280691 TI - Improvements in manual dexterity relate to improvements in cognitive planning after assisted cycling therapy (ACT) in adolescents with down syndrome. AB - We have previously reported beneficial effects of acute (i.e., single session) Assisted Cycling Therapy (ACT) on manual dexterity and cognitive planning ability in adolescents with Down syndrome (DS). In the present study, we report the chronic effects of eight weeks of ACT, voluntary cycling (VC), and no cycling (NC), on the same measures in adolescents with DS. Participants completed 8 weeks of ACT, VC, or NC. Those in the ACT and VC groups completed 30min sessions three times per week on a stationary bicycle. During ACT, the mechanical motor of the bicycle augmented the cadence to a rate which was on average 79% faster than the voluntary cadence. During VC, the participants pedaled at a self-selected rate. Unimanual dexterity scores as measured with the Purdue Pegboard test (PPT) improved significantly more for the ACT and VC groups compared to the NC group. ACT lead to greater improvements than VC and NC in the assembly sub-test, which is a task that requires more advanced temporal and spatial processing. The ACT group improved significantly more than the VC group and non-significantly more than the NC group in cognitive planning ability as measured by the Tower of London test (ToL). There were also significant correlations between the assembly subtest of the PPT and all measures of the ToL. These correlations were stronger during post-testing than pre-testing. Pre-post changes in the combined PPT score and ToL number of correct moves correlated positively in the ACT group. These results support the efficacy of the salutary effects of ACT on global fine motor function and executive function in DS. Additionally, the performance on complex bimanual dexterity tasks appears to be related to the capacity of cognitive planning ability. This research has important implications for persons with movement deficits that affect activities of daily living. PMID- 26280692 TI - Active involvement of people with intellectual disabilities in health research - A structured literature review. AB - Actively involving people with intellectual disabilities (ID) in health research, also known as inclusive health research, is increasingly popular. Currently, insight into experiences of this type of research is scarce. To gain insight into this topic, a structured literature review was conducted focussing on (1) existing theories, (2) inclusive methods, (3) added value and (4) barriers and facilitators. Literature published between January 2000 and January 2014 was included covering keywords related to ID and inclusive health research. Searches were performed in Pubmed, CINAHL, PsycINFO, EMBASE and MEDLINE databases, resulting in 26 included papers. Papers were quality assessed and analysed using qualitative data analysis software. Four theories were often simultaneously addressed: participatory research, emancipatory research, inclusive research and Arnstein's ladder. Barriers and facilitators could be divided into preparing, undertaking and finalising phases of research. Authors indicated that their motivation to conduct inclusive health research was based on demands by policy and funding bodies or was based on ethical considerations (i.e., ethical notions and giving people with ID a voice). Upon completion, authors perceived increased quality and validity of their research and several benefits for stakeholders (i.e., people with ID, researchers and healthcare professionals). Overall, there was consistency in their perception of the most important aspects of inclusive health research. Based on the analysis of included papers, four recommendations of inclusive health research with people with ID were found. Inclusive health research should be: (1) tailoring to the specific study; (2) anticipating all stakeholders; (3) considering its added value; and (4) providing insight into its process. PMID- 26280693 TI - Factors influencing waiting times for diagnosis of Autism Spectrum Disorder in children and adults. AB - AIMS: To identify the main factors predicting delays in diagnosis for Autism Spectrum Disorder (ASD) at three stages in the diagnostic process: wait for first appointment; assessment duration, and total wait for diagnosis. METHOD: Data were gathered from 150 case notes (80 child and 70 adult cases) from 16 diagnosing services across Scotland. RESULTS: Having more information pre-assessment was associated with a reduced duration of the diagnostic process for children. This relationship was partially mediated by a reduction in the number of contacts required for diagnosis. In adults, having more factors associated with ASD (increased risk) reduced the wait time from referral to first appointment, but increased the overall duration of the diagnostic process. The latter relationship was partially mediated by an increase in the number of contacts required for diagnosis. CONCLUSION: Within children's services, increasing the amount of relevant information available pre-assessment is likely to reduce total duration of the assessment process by reducing number of contacts required. Having a high risk of ASD as an adult appears to result in being seen more quickly following referral, but also to increase the number of contacts needed and assessment duration. As a result, it increases and total duration overall. PMID- 26280695 TI - Misguided statements construed as evidence-driving policy that affects patient care. PMID- 26280694 TI - Application of Volumetric Modulated Arc Therapy and Simultaneous Integrated Boost Techniques to Prepare "Safe Margin" in the Rabbit VX2 Limb Tumor Model. AB - BACKGROUND: In this study, we aimed to establish the rabbit VX2 limb tumor model, and then prepare a "necrotic zone" as a safe margin by volumetric modulated arc therapy and simultaneous integrated boost (VMAT-SIB) technique applied in the areas where the tumor is located adjacent to the bone (GTVboost area). MATERIAL AND METHODS: Rabbits in the control group (n=10) were not treated, while those in the test group (n=10) were treated with the SIB schedule delivering a dose of 40Gy, 35Gy, 30Gy, and 25Gy to the GTVboost, GTV (gross tumor volume), CTV (clinical target volume), and PTV (planning target volume) in 10 fractions. Magnetic resonance diffusion-weighted imaging (MRDWI), 3-dimensional power Doppler angiography (3D-PDA), and histological changes were observed after radiotherapy. RESULTS: After radiotherapy, the two groups showed a significant difference in the GTVboost area. In the test group, the tumor necrosis showed a significantly low signal in DWI and high signal in apparent diffusion coefficient (ADC) maps. The 3D-PDA observation showed that tumor vascular structures decreased significantly. Histological analysis demonstrated that a necrotic zone could be generated in the GTVboost area, and microscopic examination observed cell necrosis and fibroplasia. CONCLUSIONS: This studies demonstrated the feasibility of using VMAT-SIB technique in the rabbit VX2 limb tumor model. The formation of a necrotic zone can be effectively defined as safe margin in the GTVboost area. showing potential clinical applicability. PMID- 26280698 TI - Did you notice that CMS's medically unlikely edits were significantly revised? PMID- 26280699 TI - Randomized, controlled study of innovative spray formulation containing ozonated oil and alpha-bisabolol in the topical treatment of chronic venous leg ulcers. AB - OBJECTIVE: Ozone therapy has a large clinical application in many therapeutic areas because of its well-known antimicrobial, immunological, and oxygenating properties. Recently, interest has grown regarding the application of ozonated oil for vascular leg ulcer treatment. The efficacy of an innovative spray formulation of ozonated oil and alpha-bisabolol combination in the topical treatment of chronic venous leg ulcers was evaluated compared with standard epithelialization cream. DESIGN: A randomized controlled trial was conducted. SETTING: A total of 29 patients older than 18 years with chronic venous leg ulcers for less than 2 years' duration were assessed. PATIENTS: Patients were randomized to receive daily application of both ozonated oil and alpha-bisabolol or the control cream (vitamin A, vitamin E, talc, and zinc oxide) for 30 days. MAIN OUTCOME MEASURES: Patients were evaluated on 4 different visits: at days 0, 7, 14, and 30. At each visit, the wound surfaces were measured. Wound area ratio and the speed of ulcer healing were calculated. MAIN RESULTS: At the end of treatment, the proportion of patients with complete ulcer healing was higher with ozonated oil and alpha-bisabolol formulation (25% vs 0%). Furthermore, the changes in ulcer surface area were significant for ozonated oil and alpha bisabolol formulation only (P < .05), in particular, observing a significant and progressive reduction of the wound surface by 34%, 59%, and 73%, after 7, 14, and 30 days of treatment, respectively. CONCLUSION: The innovative spray formulation of ozonated oil and alpha-bisabolol combination shows promise as an important new therapeutic option in the adjuvant treatment of venous ulcers. PMID- 26280700 TI - Comparison of the cytotoxicities and wound healing effects of hyaluronan, carbomer, and alginate on skin cells in vitro. AB - OBJECTIVE: To compare the cytotoxicities and efficacy of hyaluronan (HA), carbomer, and sodium alginate on repairing thermal-injured cells and promoting cell migration. DESIGN: The 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetra zoliumromide method was used to evaluate the cytotoxicities of HA, carbomer, and sodium alginate on L929 mouse fibroblasts and their repairing ability to thermal injured HaCaT keratinocytes. A scratch test was used to observe the effects of the 3 materials on cell migration. RESULTS: Hyaluronan with different molecular weights were nontoxic, even at the concentration of 0.5%, whereas carbomer and sodium alginate showed mild or moderate cytotoxicities when their concentrations were higher than 0.1%. Cell viability and cell density of the thermal-injured keratinocytes treated with HA (600, 1070, and 1500 kDa) were increased significantly compared with that of model control (P < .05), whereas carbomer aggravated cell injury, and sodium alginate had no obvious repairing ability. Hyaluronan promoted cell migration significantly with higher cell density in the scratch area, compared with the control after culture for 48 hours; both carbomer and sodium alginate inhibited the cell migration, and carbomer altered the cell morphology completely. CONCLUSIONS: Hyaluronan can repair cell injury and promote cell migration and proliferation. It also has good biocompatibility. As a new type of hydrogel matrix, HA is superior to carbomer and sodium alginate if it is used in wound caring preparations. PMID- 26280701 TI - Secondary analysis of office of inspector general's pressure ulcer data: incidence, avoidability, and level of harm. AB - PURPOSE: To provide information about a secondary analysis of pressure ulcer data regarding incidence, avoidability, and level of harm. TARGET AUDIENCE: This continuing activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES: After participating in this educational activity, the participant should be better able to:1. Summarize the data provided in the Office of Inspector General (OIG) study regarding incidence of pressure ulcers (PrUs) found in hospitals and skilled nursing facilities (SNFs).2. Identify the classification systems used that designate levels of harm to patients and the avoidability of PrUs. OBJECTIVE: To investigate in greater detail the government data on pressure ulcer (PrU) incidence, avoidability, and level of harm. DESIGN: The authors performed a secondary analysis of PrU data published in 2 studies by the Office of Inspector General (OIG) on adverse events in hospitals and skilled nursing facilities (SNFs). SETTING: Acute care hospitals and Medicare-certified SNFs across the United States. PATIENTS: The hospital sample included 780 Medicare beneficiaries randomly selected from 999,645 discharges during October 2008. The SNF population included 653 Medicare beneficiaries randomly selected from 100,771 patients whose stay began within 1 day of hospital discharge, who had a length of stay of 35 days or less, and whose stay ended in August 2011. MAIN OUTCOME MEASURES: Pressure ulcer incidence with stage, location, avoidability, and level of harm using the Modified National Coordinating Council for Medication Errors Reporting and Prevention Index. MAIN RESULTS: The PrU incidence in hospitals was 2.9%, and the incidence in SNFs was 3.4%. Most PrUs were Stages I and II, with 78.3% in hospitals and 54.5% in SNFs. The avoidability of PrUs was similar in both locations, with 39.1% unavoidable in hospitals and 40.9% unavoidable in SNFs. All hospital-acquired PrUs and 90.9% of SNF-acquired PrUs were designated level E on the National Coordinating Council for Medication Errors Reporting and Prevention Index, indicating a temporary harm event. CONCLUSIONS: The OIG studies captured few Stage III PrUs and no Stage IV PrUs, and they underestimate the level of harm generated from PrUs in hospitals and SNFs. The studies offer a structured algorithm for avoidability determination, but lack measures of reliability and validity. Nonetheless, the high rate of unavoidable ulcers leads to questions on the reliability of PrUs as a quality indicator. There are several weaknesses in OIG methodology with regard to PrUs; however, its structured algorithm can be viewed as a starting point for future studies of PrU avoidability. PMID- 26280703 TI - Know your coverage policies. PMID- 26280704 TI - A major host plant volatile, 1-octen-3-ol, contributes to mating in the legume pod borer, Maruca vitrata (Fabricius) (Lepidoptera: Crambidae). AB - Previous studies on the legume pod borer, Maruca vitrata Fabricius (Lepidoptera: Crambidae), a serious pest of cowpea, Vigna unguiculata (L.) Walp. (Fabales: Fabaceae), in sub-Saharan Africa have focused on sex pheromones, but the role of the host plant on sexual behavior has not been explored. We investigated this interaction in the laboratory using behavioral assays and chemical analyses. We found that the presence of cowpea seedlings and a dichloromethane extract of the leaf increased coupling in the legume pod borer by 33 and 61 %, respectively, compared to the control, suggesting the involvement of both contact and olfactory cues. We used coupled gas chromatography-electroantennographic detection (GC/EAD) and GC-mass spectrometry (GC/MS) to identify compounds from the cowpea leaf extract, detected by M. vitrata antenna. We found that the antennae of the insect consistently detected four components, with 1-octen-3-ol identified as a common and dominant component in both the volatiles released by the intact cowpea plant and leaf extract. We therefore investigated its role in the coupling of M. vitrata. In dose-response assays, 1-octen-3-ol increased coupling in M. vitrata with increasing dose of the compound compared to the control. Our results suggest that the cowpea volatile 1-octen-3-ol contributes to M. vitrata sexual behavior. PMID- 26280705 TI - Frequency and Cause of Persistent Symptoms in Celiac Disease Patients on a Long term Gluten-free Diet. AB - GOALS: To estimate the frequency and cause of nonresponsive celiac disease (CD). BACKGROUND: Treatment of CD is based on life-long adherence to a gluten-free diet (GFD). Some celiac patients experience persistence of symptoms despite a GFD. This condition is defined as nonresponsive CD. STUDY: Celiac patients on a GFD for at least 12 months underwent diet compliance assessment, laboratory tests, breath tests, endoscopic, and histologic evaluations according to the symptoms/signs reported. RESULTS: Seventy of 321 (21.8%) patients had persistent or recurrent symptoms/signs. The cause of symptom persistence was evaluated in 56 of 70 patients. Thirteen of 56 (23%) patients were antiendomysial antibody positive. Among the patients with negative serology, 1 had fibromyalgia, and 3 had evidence that disproved the diagnosis of CD. The remaining 39 patients with negative serology underwent duodenal biopsy sampling, which evidenced histologic alterations in 24 patients. Among the 15 patients with normal histology 3 were lactose intolerant, 9 had irritable bowel syndrome, 2 had gastroesophageal reflux disease, and in 1 patient a cause for the persistent symptom was not identified. In patients with confirmed diagnosis of CD, exposure to dietary gluten was the main cause of persistence of symptoms/signs, and consistently after dietary modification, symptoms resolved in 63% of the patients at later time points during follow-up. CONCLUSION: Nonresponsive CD occurs in nearly one fifth of celiac patients on GFD and its occurrence suggests further investigations to optimize the management of celiac patients. PMID- 26280706 TI - The Association of Drugs With Severity and Specific Causes of Acute Lower Gastrointestinal Bleeding: A Prospective Study. AB - OBJECTIVES: Studies on the association of acute lower gastrointestinal bleeding (ALGIB) and drugs are scarce. We aimed to investigate the association of drugs and ALGIB, especially regarding specific causes of ALGIB, and their role in the severity of ALGIB. MATERIALS AND METHODS: The study was prospective and included all patients undergoing colonoscopy in 2010 and 2013 at the National University Hospital of Iceland. Use of nonsteroidal anti-inflammatory drugs (NSAIDs), low dose aspirin (LDA), and warfarin before ALGIB was registered. Clinically significant bleeding was defined as: hemoglobin <100 g/L, hemodynamic instability, blood transfusion, surgery, or death. RESULTS: Overall, 2392 patients underwent 2751 colonoscopies, of those, 325 (14%) had ALGIB, mean age 64 years (+/-20). The commonest diagnoses were diverticulosis (22%) and ischemic colitis (14%). In multivariate analysis, NSAIDs, LDA, and warfarin use was associated with ALGIB, odds ratio (OR) 3.3 [95% confidence interval (95% CI), 1.99-5.82], OR 1.5 (95% CI, 1.01-2.13), and OR 2.7 (95% CI, 1.61-4.57), respectively. Clinically significant bleeders were more likely than nonclinically significant bleeders to use NSAIDs or LDA+warfarin, OR 2.3 (95% CI, 1.26-3.76) and OR 33.0 (95% CI, 6.74-595), respectively. Patients with diverticular bleeding had greater odds than controls of NSAID, LDA, and warfarin use, OR 8.3 (95% CI, 3.8-18.3), OR 2.1 (95% CI, 1.15-3.67), and OR 2.6 (95% CI, 1.24-5.56), respectively. Patients with ischemic colitis were more likely than controls to use LDA, OR 2.3 (95% CI, 1.14-4.45). CONCLUSIONS: NSAIDs, LDA, and warfarin were associated with ALGIB and diverticular bleeding. These drugs may have a role in other etiologies of ALGIB and seem to increase the risk of clinically significant bleeding. PMID- 26280708 TI - Initial Findings of an Open-Label Trial of Low-Dose Naltrexone for Symptomatic Mesenteric Panniculitis. PMID- 26280707 TI - Prophylactic Efficacy of 3- or 5-cm Pancreatic Stents for Preventing Post-ERCP Pancreatitis: A Prospective, Randomized Trial. AB - BACKGROUND AND STUDY AIMS: Prophylactic pancreatic stent placement is effective for preventing postendoscopic retrograde cholangiopancreatography pancreatitis (PEP). The most effective type of stent, however, remains unclear. Therefore, we prospectively compared the prophylactic efficacy for PEP prevention between short (3 cm) and long (5 cm) pancreatic stent. PATIENTS AND METHODS: Between July 2012 and June 2014, 240 consecutive patients requiring therapeutic endoscopic retrograde cholangiopancreatography to remove a choledocholith or for bile drainage for obstructive jaundice were prospectively enrolled and randomized to undergo prophylactic insertion with unflanged, 5 Fr, 3 or 5-cm pancreatic stent. An efficacy of each stent for preventing PEP was evaluated as a primary endpoint. The period until stent dislodgement and the total adverse event rate were also evaluated as a secondary endpoint. RESULTS: Per-protocol analysis revealed that the PEP rate was significantly lower with the short stent than with the long stent (2.0% vs. 8.8%, P=0.035), although they were not significantly different in intention-to-treat analysis. The adverse event rate excluding PEP did not differ significantly between groups (3.0% vs. 0.9%, P=0.293). The median period until dislodgement of the short stent was significantly shorter than that of the long stent (2 vs. 4 d, P<0.001). CONCLUSIONS: The present study revealed a superiority of 3-cm stents compared with 5-cm stents for prophylactic pancreatic stent. On the basis of the past reports and the result of the present study, we recommend using a 5 Fr, 3-cm unflanged stent.This study was registered on the UMIN Clinical Trial Registry (UMIN000008290). PMID- 26280709 TI - Remission of symptoms in community-based psychosocial rehabilitation services for individuals with schizophrenia. AB - OBJECTIVE: The aims of this study were to determine the prevalence of remission in individuals with schizophrenia at baseline and 6 months after admission to community-based psychosocial rehabilitation and whether baseline intrapersonal and environmental resources predicted remission at 6 months, controlling for relevant demographic and clinical variables. METHOD: The sample featured 187 individuals with schizophrenia spectrum disorder. To determine remission status, consensus-based criteria proposed by the Remission in Schizophrenia Working Group were adapted to identify predictors of remission outcomes, direct binary logistic regression analysis was performed. RESULTS: Findings indicated that 34.57% and 55.61% of the sample was in remission at baseline and 6 months, respectively. Remission at 6 months was predicted by shorter length of illness and being in remission at admission. CONCLUSIONS: Remission of schizophrenia is an achievable outcome in community psychosocial rehabilitation settings. Clinical characteristics exerted a significantly stronger influence on remission outcomes compared with psychosocial factors. PMID- 26280710 TI - A meta-analysis of confidence and judgment accuracy in clinical decision making. AB - The overconfidence bias occurs when clinicians overestimate the accuracy of their clinical judgments. This bias is thought to be robust leading to an almost universal recommendation by clinical judgment scholars for clinicians to temper their confidence in clinical decision making. An extension of the Meta-Analysis of Clinical Judgment (Spengler et al., 2009) project, the authors synthesized over 40 years of research from 36 studies, from 1970 to 2011, in which the confidence ratings of 1,485 clinicians were assessed in relation to the accuracy of their judgments about mental health (e.g., diagnostic decision making, violence risk assessment, prediction of treatment failure) or psychological issues (e.g., personality assessment). Using a random effects model a small but statistically significant effect (r = .15; CI = .06, .24) was found showing that confidence is better calibrated with accuracy than previously assumed. Approximately 50% of the total variance between studies was due to heterogeneity and not to chance. Mixed effects and meta-regression moderator analyses revealed that confidence is calibrated with accuracy least when there are repeated judgments, and more when there are higher base rate problems, when decisions are made with written materials, and for earlier published studies. Sensitivity analyses indicate a bias toward publishing smaller sample studies with smaller or negative confidence-accuracy effects. Implications for clinical judgment research and for counseling psychology training and practice are discussed. PMID- 26280711 TI - Quantitative host cell protein analysis using two dimensional data independent LC MS(E). AB - Host cell proteins (HCPs) are bioprocess-related impurities arising from cell death or secretion from nonhuman cells used for recombinant protein production. Clearance of HCPs through downstream purification (DSP) is required to produce safe and efficacious therapeutic proteins. While traditionally measured using anti-HCP ELISA, more in-depth approaches for HCP characterization may ensure that risks to patients from HCPs are adequately assessed. Mass spectrometry methods provide rationale for targeted removal strategies through the provision of both qualitative and quantitative HCP information. A high pH, low pH, reversed-phase data independent 2D-LC-MS(E) proteomic platform was applied to determine HCP repertoires in the Protein A purified monoclonal antibody (mAb) samples as a function of culture harvest time, elution buffer used for DSP and also following inclusion of additional DSP steps. Critical quality attributes (CQAs) were examined for mAbs purified with different Protein A elution buffers to ensure that the selected buffers not only minimized the HCP profile but also exhibited no adverse effect on product quality. Results indicated that an arginine based Protein A elution buffer minimized the levels of HCPs identified and quantified in a purified mAb sample and also demonstrated no impact on product CQAs. It was also observed that mAbs harvested at later stages of cell culture contained higher concentrations of HCPs but that these were successfully removed by the addition of DSP steps complementary to Protein A purification. Taken together, our results showed how mass spectrometry based methods for HCP determination in conjunction with careful consideration of processing parameters such as harvest time, Protein A elution buffers, and subsequent DSP steps can reduce the HCP repertoire of therapeutic mAbs. PMID- 26280713 TI - The spine: so many areas left to explore! PMID- 26280712 TI - Synthesis and Structural Elucidation of Triazolylmolybdenum(VI) Oxide Hybrids and Their Behavior as Oxidation Catalysts. AB - A large family of bifunctional 1,2,4-triazole molecular tectons (tr) has been explored for engineering molybdenum(VI) oxide hybrid solids. Specifically, tr ligands bearing auxiliary basic or acidic groups were of the type amine, pyrazole, 1H-tetrazole, and 1,2,4-triazole. The organically templated molybdenum(VI) oxide solids with the general compositions [MoO3(tr)], [Mo2O6(tr)], and [Mo2O6(tr)(H2O)2] were prepared under mild hydrothermal conditions or by refluxing in water. Their crystal structures consist of zigzag chains, ribbons, or helixes of alternating cis-{MoO4N2} or {MoO5N} polyhedra stapled by short [N-N]-tr bridges that for bitriazole ligands convert the motifs into 2D or 3D frameworks. The high thermal (235-350 degrees C) and chemical stability observed for the materials makes them promising for catalytic applications. The molybdenum(VI) oxide hybrids were successfully explored as versatile oxidation catalysts with tert-butyl hydroperoxide (TBHP) or aqueous H2O2 as an oxygen source, at 70 degrees C. Catalytic performances were influenced by the different acidic-basic properties and steric hindrances of coordinating organic ligands as well as the structural dimensionality of the hybrid. PMID- 26280714 TI - Non-union of osteoporotic vertebral fractures - identification and treatment of an underestimated pathology in elderly patients with persistent back pain. AB - OBJECTIVE: Non-union of osteoporotic vertebra fractures are a seldom entity. However, when back pain persists in the course of conservatively treated osteoporotic vertebra fractures, a non-union should be considered. We thus sought to validate our diagnostic algorithm in patients with known osteoporotic vertebra fractures presenting persistent back pain and advert to the diagnosis and treatment of vertebral non-unions. PATIENTS AND METHODS: Patients admitted with preexisting osteoporotic vertebra fractures and therapy-resistant back pain were retrospectively analysed. All admitted patients were subject to standard plain radiographs in erect position and conventional CT or MR imaging of the spine, respectively. In addition, patients with suspected non-union were subject to lateral fulcrum radiographs in supine position. RESULTS: From a total of 172 admitted patients, four patients presented with non-union of a fractured osteoporotic vertebra (2%). The subsequent surgical therapy included cement augmented rod-and-screw stabilization, with or without additional correction of deformity, and kyphoplasty (N = 3) or kyphoplasty alone (N = 1). All surgical interventions were successful in pain reduction and allowed immediate and improved postoperative mobilisation. CONCLUSIONS: Non-union of osteoporotic vertebra fractures must be considered when symptoms outlast conservative treatment. In these cases, plain lateral fulcrum radiographs are a simple and effective adjunct to the conventional diagnostic methods. Surgical stabilization then proves to be the effective treatment of choice. PMID- 26280715 TI - Fate of kyphosis in tuberculosis of subaxial cervical spine treated non operatively. AB - OBJECTIVE: Observation of post treatment kyphotic angle in patient of cervical spine tuberculosis managed non operatively. BACKGROUND: The incidence of tuberculosis of cervical spine is about 6-9%. The most dreaded complications of spinal tuberculosis are neural involvement and spinal deformity. Due to destruction of the vertebra tuberculosis of spine usually leads to variable amount of kyphotic deformity. METHODS: We retrospectively reviewed 13 patients with clinico-radiological diagnosis of cervical spine tuberculosis managed in our centre between 2004 to 2011. The patients were started on antitubercular therapy. Crutchfield tongs traction was applied 8 to 12 weeks followed by mobilization with four post collar. The kyphotic angles were measured by radiograph at presentation and last available follow up radiograph. OBSERVATIONS: The mean age of the patients was 20 years. C3-C4 vertebra was the most commonly involved area. One patient had single vertebra involvement, five patients had two vertebrae involvement, five patients had three vertebrae involvement and two patients had four vertebrae involvement. The average number of vertebrae involved was 2.6 vertebrae. 9 out of 13 patients had neural deficit at the time of initial presentation. The mean follow up was 21.23 months (12 to 42 months). All patients responded favorably and had neural recovery. At final follow up, 10 out of 13 patients had improvement in kyphotic angle, two patients had deterioration of kyphotic angle and one patient had no change in kyphotic angle. Only one patient had significant deterioration in kyphotic angle. CONCLUSIONS: Non operative treatment of cervical spine tuberculosis by initial traction and antitubercular therapy improves the pretreatment deformity irrespective of the number of vertebra involved. PMID- 26280716 TI - Growing rod instrumentation in the treatment of early onset scoliosis. AB - The goal of the treatment of early onset scoliosis (EOS) is correction of the deformity while still allowing for spinal growth. The aim of this study was to determine the safety and effectiveness of the single and dual growing rod techniques and which technique was the most effective in the management of EOS respectively. From 2003 to 2009, 23 patients underwent single (15) or dual (8) growing rod procedures using a pedicle screw construct and tandem connectors. The etiology of the patients' spinal deformities were as follows; infantile, juvenile idiopathic, congenital and neuromuscular. Clinical evaluation included age, sex, diagnosis, follow-up, number and frequency of lengthenings, and complications. Radiographic evaluation included measured changes in Cobb angle, kyphosis, lordosis, frontal and sagittal balance. Overall 46 lengthening procedures were performed, the average number of lengthening procedures being 2.1 +/- 1.14 per patient. The average time between two lengthening procedures was 13 (2-28) months. Average follow-up time was 40.8 +/- 20.6 months.The mean coronal Cobb angle was improved from 64.8 degrees +/- 16.6 degrees to 39.7 degrees +/- 16.4 degrees .Statistically, at the final follow-up, early postoperative measurements in the coronal plane were better in the dual growing rod group than in the single rod group. Nine patients underwent fusion surgery. Their mean age was 11 (10-14) years, with a follow-up of 34.6 (14-54) months. The mean Cobb angle before fusion was 58.7 degrees (40 degrees -75 degrees ). There were 0.9 complications per patient in all groups, 0.38 in the dual rod and 1.2 in the single rod group, respectively. Dual growing rods result in better deformity correction and stability of correction with an acceptable complication rate. PMID- 26280717 TI - Should a Lumbar MRI for back pain routinely include the sacro-iliac joint? AB - BACKGROUND: Back pain is a common problem and has been shown to affect approximately 85% of the adult population at any one time. The source of this pain can be difficult to identify and the sacroiliac joint (SIJ) has been proposed as a possible pain source. Its percentage contribution to lower back pain is controversial. Clinical provocative tests for SIJ pathology have been developed but these have high intra and inter-observer variability and the significant of positive findings is unclear. This study proposes that the SIJ should not be imaged as part of a routine MRI lumbar spine series. METHODS: We retrospectively reviewed the images of 353 patients who had MRI lumbar spine scans. 130 had the SIJ imaged. We recorded the clinical findings and diagnosis at referral. We reviewed the images and documented the radiological findings. RESULTS: SI joint pathology was most frequently identified when clinical suspected. Overall SIJ pathology found on MRI in only 0.02% of patients. CONCLUSIONS: We conclude that routinely imaging the SIJ in MRI lumbar spine series is not cost-effective or a useful use of resources. The SIJ should be imaged only if significant clinical findings are demonstrated. PMID- 26280718 TI - The surgical treatment of far lateral lumbar disc herniation: 33 cases. AB - Surgical approaches to far lateral disc herniation are challenging because of the anatomical limitations in the region. We describe an extraforaminal approach for far lateral lumbar disc herniation (FLLDH) in a group of patients and discuss the results in patients with far lateral disc protrusion or extrusion operated on by an approach to the extraforaminal region via an intertransverse route with median or paramedian incisions. The two methods are compared in terms of the pre- and postoperative visual analogue scale (VAS) pain scores, duration of the operation, amount of bleeding, and long-term functional recovery. In addition, data on age, incidence, radiological features and clinical signs and symptoms are compared with reported series. Between January 2006 and January 2011, 33 patients (18 females, 15 males; mean age, 51.2 years) underwent surgery for FLLDH. The majority of patients had herniation at disc levels L3-4 (12 patients) or L4-5 (15 patients). All patients were operated on via either median-paramuscular (20 patients, 61%) or paramedian-intermuscular (13 patients, 39%) approaches. Overall, the mean VAS score improved from 7.3 preoperatively to 2.8 in the short term. Analyzing the long-term functional outcome of surgery according to the MacNab Criteria, the recovery was excellent, good, fair, and poor in 18, 11, 4, and 0 patients, respectively. The far-lateral approach for FLLDH is a safe, effective procedure that avoids the risk of secondary spinal instability. In treating FLLDH, the use of a long median incision together with an extraforaminal approach is safer and less invasive than a laminectomy together with a medial or total facetectomy. PMID- 26280719 TI - Kyphoplasty versus vertebroplasty in the treatment of painful osteoporotic vertebral compression fractures: two-year follow-up in a prospective controlled study. AB - A total of 112 patients with a single-level osteoporotic vertebral compression fracture who did not respond to conservative therapy were included and allocated to either kyphoplasty or vertebroplasty treatment. The Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) were used to assess back pain and disability. Anterior, midline, posterior vertebral body heights, and kyphotic angle at the fractured vertebra were measured for radiographic evaluation. Clinical and radiographic follow-up examinations were performed postoperatively at 3, 6, 12 and 24 months. Complications and patient satisfaction with the surgical procedure were also recorded. The follow-up rate was 73.3% in the kyphoplasty group and 80.8% in the vertebroplasty group (P = 0.737). There were no significant differences between the 2 groups with regard to improvement in VAS and ODI scores (P > 0.05) at all postoperative intervals. Both treatment groups achieved marked vertebral height restoration and kyphotic angle reduction, but the radiographic parameters were significantly better in the kyphoplasty group (P < 0.05). The incidence of asymptomatic cement leakage per treated vertebrae in the kyphoplasty group was 11.4% versus 31% in the vertebroplasty group (P < 0.001). Three adjacent level fractures in the kyphoplasty group and 2 in the vertebroplasty group occurred during 2-year follow-up, and no difference in patient satisfaction was detected between the 2 groups. Kyphoplasty and vertebroplasty achieved similar improvement of clinical outcomes and patient satisfaction at 2 years after surgery, albeit kyphoplasty had more ability to markedly reduce vertebral deformity and resulted in less cement leaks compared with vertebroplasty. PMID- 26280720 TI - Comparison of two treatment strategy for Lenke I adolescent idiopathic scoliosis. AB - The aim of the study study is to determine whether bilateral pedicle screw placement and posterior only spinal fusion improves sagittal correction parameters compared to alternate posterior segmental fixation in adolescent idiopathic scoliosis. 49 patients with Lenke Type 1 main thoracic curves who underwent single stage posterior only instrumentation and spinal fusion at a single center were retrospectively evaluated according to coronal radiological parameters. Patients divided into two groups of treatment strategy. Bilateral segmental fixation group's results were similar to alternate fixation group. Although quality of life or cosmetic evaluation of patients not involved in this study, alternate fixation provides similar results as bilateral segmental fixation in adolescen idiopathic scoliosis. PMID- 26280721 TI - The treatment of osteoporotic thoracolumbar severe burst fractures with short pedicle screw fixation and vertebroplasty. AB - BACKGROUND: To investigate the clinical and radiological results of short pedicle screw fixation and vertebroplasty in osteoporotic thoracolumbar severe burst fractures. METHODS: From September 2006 to August 2010, 19 consecutive patients sustained osteoporotic thoracolumbar severe burst fractures with or without neurologic deficit and were included in this prospective study. All patients underwent short pedicle screw fixation and vertebroplasty. Segmental kyphosis, AVBHr and PVBHr, and Canal compromise were calculated on radiographs pre operatively, post-operative and at final follow up. VAS, ODI and SF-36 were calculated pre-operatively and at final follow up. RESULTS: Mean operative time was 70.8 min (range 60~100 min) and mean blood loss was 92 ml (range 60~160 ml). The mean duration of their hospital stay was 4.5 days (range 3-7 days). The operative incisions were healing well. Average follow up time was 40.1 months (range 24~72 months). The AVBHr was corrected from preoperative (48.1 +/- 6.8) % to postoperative (94.1 +/- 1.7) % (P < 0.001). The PVBHr was corrected from preoperative (62.7 +/- 4.8) % to postoperative (92.8 +/- 1.8) % (P < 0.001). Canal compromise was corrected from preoperative (37.3 +/- 5.8) % to postoperative (5.9 +/- 2.3) % (P < 0.001). The segmental kyphosis was corrected from preoperative (20.6 +/- 5.3) degree to postoperative (2.0 +/- 3.2) degree (P < 0.001). VAS scores were reduced from preoperative 7.21 +/- 0.86 to 2.21 +/- 0.98 at final follow up (P < 0.001). SF-36 Bodily pain was reduced from preoperative 75.31 +/- 13.85 to 13.74 +/- 13.24 at final follow up (P < 0.001), and SF-36 Role Physical was reduced from preoperative 59.21 +/- 26.63 to 19.74 +/ 22.94 at final follow up (P < 0.001). The ODI scores were reduced from preoperative 81.68 +/- 4.44 to 15.37 +/- 5.54 at final follow up (P < 0.001). All 4 patients with partial neurological deficit initially had improvement. Cement leakage was observed in 3 cases (two anterior to vertebral body and one into the disc without sequela). There were no instances of instrumentation failure and no patient had persistent postoperative back pain. CONCLUSIONS: Vertebroplasty and short pedicle screw fixation has the advantages of both radiographic and functional results for treating osteoporotic thoracolumbar severe burst fractures using a purely posterior approach. PMID- 26280722 TI - Computed tomography-guided percutaneous focal catheter infusion in the treatment of spinal tuberculosis. AB - The study aimed to investigate the efficacy of computed tomography (CT)-guided percutaneous focal catheter infusion for the treatment of spinal tuberculosis. Clinical and follow-up data from 27 spinal tuberculosis patients who underwent CT guided intervertebral catheterized infusion chemotherapy from May 2008 to October 2011 were retrospectively analyzed; treatment included pure intervertebral infusion chemotherapy and catheter drainage for continuous abscess washing during infusion chemotherapy. All surgeries were successfully completed under CT guidance without complications. The C-reactive protein levels of most patients rebounded within the first postoperative week but significantly decreased after the second and fourth postoperative weeks. CT-guided percutaneous focal catheter infusion was effective for the treatment of spinal tuberculosis and induced little trauma; this treatment could also relieve the symptoms and improve the quality of life of elderly patients with poor general conditions. PMID- 26280723 TI - Geographic Origin of Publications in Major Spine Journals. AB - Aim of the present study was to assess the contribution of each country in the field of spine surgery. Three major spine journals were included in our study and the search conducted in PubMed for a 5-year period (2007-2012). Publications on spine surgery were assessed according to the country. A total of 6312 articles were identified and 5842 were included. Fifteen countries generated 86.9% of publications, with 31.7% by the United States, followed by Japan (9.6%), China (8.1%) and Canada (5.2%). After correction for population size Switzerland (19 studies per 106 inhabitants), the Netherlands (10), Sweden (9), Canada (9) and Australia (6) ranked the top. The USA was placed 7th after correction for population size. Small European countries with modest research funding and non native English speaking population are more productive in relation to their population size, despite the fact that the contribution of USA is the greatest in the field of the major peer-reviewed indexed spine surgery journals. PMID- 26280724 TI - Anatomical assessment of iliac crest graft size for anterior spondylodesis. AB - Standard procedure for monosegmental anterior spondylodesis often combines anterior stabilization with autologous iliac crest graft. Recent publications defined a minimum size of the graft as a technical specification for this procedure. The cross sectional area of the graft to be transplanted should be at least 23.9% of the cross sectional area of the vertebral bodies to be fused. We investigated whether the required minimum size of autologous graft, as identified both experimentally and clinically, is compatible with the anatomical conditions in central european patients. Computed tomography scans (n = 348) of polytraumatized patients were obtained in the course of initial diagnosis. The scans were evaluated for vertebral body size and the possible size of autologous bone graft in the region of the anterior superior iliac crest. The evaluation of 348 CT scans demonstrated that 95% of the quantified iliac crest grafts would achieve the size recommended for anterior spinal fusion between T10 and T12. In 90% of all cases the planned iliac crest graft exceeded the size limit of 23,9% between concerning the endplates T10 and L2. In 85% the planned iliac crest graft exceeded the size limit of 23,9% between T10 and L3. The recommendation to take this value into account for monosegmental anterior spondylodesis should gain in importance in clinical practice. PMID- 26280725 TI - Correlation between clinical outcomes and spinopelvic parameters in osteoporosis. AB - INTRODUCTION: Little data is available on the relationship between sagittal spinopelvic parameters and health related quality of life (HRQOL) in osteoporotic patients. The aim of this study was to identify relationships between spinopelvic parameters and HRQOL in osteoporosis. MATERIAL AND METHODS: The patient and control groups comprised 138 osteoporotic patients and 40 controls. All underwent anteroposterior and lateral radiography of the whole spine, including hip joints, and completed clinical questionnaires. The radiographic parameters examined were; sacral slope, pelvic tilt, pelvic incidence, thoracic kyphosis, lumbar lordosis, and sagittal vertical axis. Lumbar spinal bone mineral density (LSBMD) and femoral neck BMD (FNBMD) of the non-dominant proximal femur were measured. A Visual Analogue Scale (VAS: 0-10) was used to assess back pain, and the Oswestry disability index (ODI) questionnaire and the Scoliosis Research Society (SRS-22) questionnaire to evaluate QOL. Statistical analysis was performed to identify significant differences between the patient and control groups. In addition, correlations between radiological parameters and clinical questionnaires were sought. RESULTS: Patients and controls were found to differ significantly in terms of sagittal vertical axis, sacral slope, pelvic tilt, lumbar lordosis, and thoracic kyphosis. However, no significant intergroup difference was observed for pelvic incidence (P > 0.05). Correlation analysis revealed significant relationships between radiographic parameters and clinical outcomes. Multiple regression analysis was performed to identify predictors of clinical outcome, and the results obtained revealed that sagittal vertical axis, sacral slope, and FNBMD significantly predicted VAS, ODI, and SRS-22 scores and that LSBMD predicted SRS-22 scores. CONCLUSIONS: Osteoporotic patients and controls were found to be significantly different in terms of sagittal spinopelvic parameters. Correlation analysis revealed significant relationships between radiographic parameters and clinical outcome variables. In particular, sagittal vertical axis, sacral slope, and FNBMD significantly predicted clinical outcomes in osteoporotic patients. PMID- 26280726 TI - Comparison of microendoscopic discectomy system and anterior open approach in treatment of unstable odontoid fracture with cannulated screw internal fixation. AB - This study intended to investigate the safety and efficacy of microendoscopic discectomy system compared with anterior open approach in the treatment of odontoid fracture with cannulated screw internal fiation. Thirty-two patients (25 male and 7 female) were enrolled and randomly assigned to different treatments. 15 patients were treated with microendoscopic discectomy system (Group MED) and 17 patients were treated with anterior open approach (Group AOA). The operating time, volume of blood loss, occurrence of complications, and fracture healing rate were compared. In Group MED, the mean operating time and blood loss volume were significant lower than those in Group AOA (P < 0.05). Nevertheless, all patients in both groups obtained bony union and cervical range of motion without significant difference statistically (P > 0.05). Three patients in Group AOA complained of transient dysphagia. We concluded that microendoscopic discectomy system for odontoid fracture treatment with cannulated screw is a safe, reliable and minimal invasive procedure compared with traditional open surgery. PMID- 26280727 TI - Study on the anatomy of the lumbosacral anterior great vessels pertinent to L5/S1 anterior interbody surgery with computer tomography angiography. AB - We investigate the anatomy of the lumbosacral anterior great vessels using computer tomography (CT) angiography before L5/S1 anterior interbody surgery. Sixty-two adult patients were selected. The location of the abdominal aortic bifurcation and common iliac venous confluence in the lumbar vertebrae and the anatomic parameters of the iliac vascular space (e.g., distances from the included angle vertex of the iliac vascular space to the median sagittal plane and to the inferior boundary of L5 and distances between the left and right iliac vessels on the inferior boundary of L5 and on the superior boundary of S1) were analysed. Overall, 67.73% of the 62 cases had an abdominal aortic bifurcation located at L4 and L4/5 intervertebral disc; 61.29%, the common iliac venous confluence located at L5. The four distances mentioned above were 0.98 cm +/- 0.38 cm, 2.01 cm +/- 1.26 cm, 3.11 cm +/- 1.35 cm and 4.34 cm +/- 1.10 cm, respectively. A classification system of types A, B and C was developed. The calculated L5/S1 intervertebral space exposure percentages of types A, B and C were 32.21%, 82.58% and 54.68%, respectively. During L5/S1 anterior interbody surgery, type B intervertebral discs can be exposed conveniently, preventing injury of the iliac vessels, which was also observed in 54.68% and 32.21% of the type C and type A discs, respectively. Because the type A intervertebral disc has minimal exposure, the risk of iliac vascular injury is relatively high in these patients. PMID- 26280728 TI - Validity of creatine kinase as an indicator of muscle injury in spine surgery and its relation with postoperative pain. AB - PURPOSE: To confirm the validity of postoperative creatine kinase (CK) values as an indicator of muscle lesion, assess the relationship of CK with variables indicating surgical invasiveness and investigate an association between CK values and excessive postoperative pain. MATERIAL AND METHODS: The study included 96 patients (mean age 62.8 years) who underwent instrumented spine fusion for degenerative lumbosacral disease. Serum CK concentration was determined on the first postoperative day. All patients received intravenous paracetamol and metamizole, and in cases of intense pain, rescue analgesia with iv meperidine. Patients were categorized according to whether or not they required rescue analgesia. Data on the number of levels fused, the duration of surgery, and operative bleeding were recorded in each patient. RESULTS: CK values were higher in men and in younger patients. Significant correlations were found between CK and the number of fused levels and duration of surgery. Only 17.7% of patients required rescue analgesia. CK levels did not significantly differ between patients who did not need rescue analgesia (1135 IU/L) and those who did (1421.5 IU/L). CONCLUSIONS: Serum CK concentration is a valid marker of surgical muscle injury and is affected by the age and sex. Factors such as the magnitude and duration of surgery show a relationship with postoperative CK values. The incidence of severe postoperative pain is not significantly related to CK level. PMID- 26280729 TI - Cement augmentation for vertebral fractures in patients with multiple myeloma. AB - Objective of our study was to assess the outcome of cement augmentation in patients with multiple myeloma. We reviewed 12 patients with 48 vertebral fractures. Mean age was 62.5 years. Average length of follow-up was 27.5 months. Expected survival was less than 12 months in 2 patients and more than 12 months in the remaining patients. After surgery mean survival was 32.5 months. Mean correction in vertebral angle was 3.6 degrees . Karnofsky score was more than 70 in 5 patients, 50-70 in 6 and less than 50 in 1 patient preoperatively, while it was more than 70 in all patients postoperatively. Preoperative mean ODI was 72%. After surgery it was 46% at 6 weeks and 14% at 12 months. All patients reported improvement in their pain status after surgery. Cement augmentation is a safe and effective way of treating symptoms of multiple myeloma, which occur due to vertebral metastases. It results in excellent pain control and improvement in quality of life. PMID- 26280730 TI - A cervical "zero-profile" cage with integrated angle-stable fixation: 24-months results. AB - The purpose of this prospective mono-centric case series study is to investigate the mid-term (minimum follow-up 24 months) safety and efficacy using a new "zero profile" stand-alone cage with integrated angle-stable fixation in single- and multilevel anterior cervical fusions. 53 consecutive patients with radiculopathy/myelopathy at one to three levels underwent an anterior cervical discectomy and fusion procedure using the "zero-profile" implant (97 levels operated). A CT-scan at 12-months was taken to assess fusion status, implant failure, subsidence and migration. The overall fusion rate was 97%. 3 out of 45 patients (6.6%) complained about mild dysphagia related symptoms at 24 months follow-up . There was no recorded incidence of hardware failure. The new cervical stand-alone anterior fusion device allows a safe anterior cervical decompression and stabilisation, a low rate of chronic dysphagia and achieves a high fusion rate. Prospective randomised trials are necessary to confirm these results. PMID- 26280731 TI - Is OPLL-induced canal stenosis a risk factor of cord injury in cervical trauma? AB - The purpose of this study is to identify the relationship between trauma severity and the degree of cord injury in patients with ossification of posterior longitudinal ligament (OPLL). Four-hundred-one patients were classified into Group A (OPLL(+)), Group B (spinal stenosis (+) and OPLL(-)), and Group C (OPLL ( ) and spinal stenosis(-)). Trauma severity and neurological injury severity were compared according to presence of OPLL and spinal stenosis. OPLL was associated with a higher incidence of neurological injury with statistical significance (p = 0.002), whereas spinal stenosis did not (p = 0.408). With Group B+C (no OPLL group) in M (minimal) trauma group as baseline, Group A in M trauma group showed about 5 times, and Group A in S (severe) trauma group showed about 16 times as many cord injury. Patients with OPLL more frequently sustained spinal cord injury from minimal trauma. PMID- 26280732 TI - Significance of spinal canal and dural sac dimensions in predicting treatment of lumbar disc herniation. AB - This retrospective study was performed to investigate the significance of quantitative MRI measurements of spinal canal and dural sac dimensions for treatment decisions and clinical outcome of lumbar disc herniation. 182 patients (111 nonsurgical patients and 71 surgical patients) were included, while 78 nonsurgical patients and 50 surgical patients were enrolled in the final follow up. The initial JOA score in nonsurgical patients was significantly superior to surgical patients (t-test: p < 0.001), whereas the final JOA score and the rate of improvement were not significantly different between the two groups of patients (t-test: p > 0.05). 88.46% of nonsurgical patients and 90.00% of surgical patients had a good or excellent outcome (chi-square test: p > 0.05). However, if the 16 recurrent cases were included, the proportions dropped to 75.82% and 84.90% for nonsurgical and surgical patients, respectively. Compared with nonsurgical patients, quantitative parameters, such as midsagittal diameter and available diameter of spinal canal, lateral recess width and cross-sectional areas of spinal canal and dural sac, were significantly smaller in surgical patients (t-test: p < 0.001), and was reflected in the initial JOA score (128 cases; Spearman rank correlation coefficient: r 0.01 = 0.486, 0.499, 0.493, 0.507, 0.484; p < 0.001). The spinal canal and dural sac dimensions were important predictive factors for treatment selection of lumbar disc herniation. PMID- 26280734 TI - Blood Components Interactions to Ionic and Nonionic Glyconanogels. AB - Nanogels are prominent examples of "smart" nanomaterials, which are designed to incorporate biologically relevant (macro)molecules for systemic delivery. Although these systems are carefully engineered, only a handful of studies discuss the blood compatibility of nanogels, and no systematic studies are available on how the presence of net or surface charges impacts the hemocompatibility of these nanomaterials. Therefore, in this study, temperature responsive, galactose based nanogels bearing net positive, negative, or neutral charges, either in the core or shell of nanogels, are prepared and are subsequently evaluated for their blood compatibility profiles. The nanogels containing neutral core and shell, cationic core with neutral shell, anionic core with neutral shell, neutral core with cationic shell, and neutral core with anionic shell are prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization approach. The evaluation of complement activation, blood clot formation, platelet activation, red blood cells aggregation, and hemolysis provides a detailed analysis of structure activity relationship of blood compatibility profile of these nanogels. The data reveal that the physical and biological (blood compatibility) properties can be carefully tuned by embedding the charges in the core of temperature-responsive nanomaterials, protected by neutral carbohydrate based shells. PMID- 26280735 TI - High-Efficiency All-Dielectric Metasurfaces for Ultracompact Beam Manipulation in Transmission Mode. AB - Metasurfaces are two-dimensional structures enabling complete control on light amplitude, phase, and polarization. Unlike plasmonic metasurfaces, silicon structures facilitate high transmission, low losses, and compatibility with existing semiconductor technologies. We experimentally demonstrate two examples of high-efficiency polarization-sensitive dielectric metasurfaces with 2pi phase control in transmission mode (45% transmission efficiency for the vortex converter and 36% transmission efficiency for the beam steering device) at telecommunication wavelengths. Silicon metasurfaces are poised to enable a versatile platform for the realization of all-optical circuitry on a chip. PMID- 26280733 TI - Progesterone and the Repression of Myometrial Inflammation: The Roles of MKP-1 and the AP-1 System. AB - Progesterone (P4) maintains uterine quiescence during pregnancy and its functional withdrawal is associated with increased prostaglandin synthesis and the onset of labor. In primary human myometrial cells, the glucocorticoid receptor (GR) rather than the P4 receptor mediates P4 antagonism of IL-1beta induced cyclooxygenase-2 (COX-2) expression, the rate-limiting enzyme in prostaglandin synthesis. We now report that P4 also acts via GR to induce MAPK phosphatase (MKP)-1 and knockdown of MKP-1 impairs the ability of P4 to repress IL-1beta-dependent COX-2 induction. Microarray analysis revealed that P4 repressed preferentially activator protein-1-responsive genes in response to IL 1beta. Consistent with these observations, we found that the ability of P4 to reduce c-Jun activation was lost upon GR as well as MKP-1 knockdown. Interestingly, c-Jun levels in human myometrial cells declined upon GR and MKP-1 knockdown, which suggests the presence of an activator protein-1 feedback loop. This is supported by our observation that c-Jun levels declined after an initial rise in primary myometrial cells treated with phorbol 12-myrisatate 13-acetate, a potent activator of c-Jun N-terminal kinase. Finally, we show that MKP-1 is an intermediate in P4-mediated repression of some but not all IL-1beta-responsive genes. For example, P4 repression of IL11 and IRAK3 was maintained upon MKP-1 knockdown. Taken together, the data show that P4 acts via GR to drive MKP-1 expression, which in turn inhibits IL-1beta-dependent c-Jun activation and COX-2 expression. PMID- 26280736 TI - Impact of a Short-Term Nutrition Education Child Care Pilot Intervention on Preschool Children's Intention To Choose Healthy Snacks and Actual Snack Choices. AB - BACKGROUND: Novel interventions within child care settings are needed for childhood obesity prevention. The aim of this study was to determine the impact of a short-term nutrition education pilot intervention on preschool-age children's snack food choices. METHODS: Children ages 3-5 years (n = 49) from one child care setting participated in a short-term nutrition education intervention (nine 30-minute interactive lessons) taught over a 2-week period. Pre-post assessments included snack knowledge and snack preference questionnaires and an observed snack selection trial to allow children to choose between a healthy and unhealthy snack choice similar to the current food environment. Children's height and weight were measured and BMI z-scores calculated. Parental reports of demographics and child's food preferences were also collected at baseline. RESULTS: Children significantly improved their preference of healthier snacks (p = 0.03) and the ability to distinguish them (p = 0.03) from other snacks. However, they did not significantly improve (p > 0.05) their snack choice between a healthy and unhealthy choice immediately after the short-term nutrition education program. Children who were younger (p = 0.003) or who had higher nutrition knowledge scores (p = 0.002) were more likely to select the healthy snack after the intervention. CONCLUSIONS: This study provides evidence that a short-term nutrition education program improves preschool children's knowledge about healthy snacks, but does not translate to immediate healthier snack selections for all children. Future research should investigate the optimal duration of a nutrition education program in a child care setting and other external influences (parents, policy) most influential on snack choice and eventual obesity risk. PMID- 26280737 TI - Synthesis and high-throughput characterization of structural analogues of molecular glassformers: 1,3,5-trisarylbenzenes. AB - We report the synthesis and characterization of an analogous series of small organic molecules derived from a well-known glass former, 1,3-bis(1-naphthyl)-5 (2-naphthyl)benzene (alpha,alpha,beta-TNB). Synthesized molecules include alpha,alpha,beta-TNB, 3,5-di(naphthalen-1-yl)-1-phenylbenzene (alpha,alpha-P), 9 (3,5-di(naphthalen-1-yl)phenyl)anthracene (alpha,alpha-A), 9,9'-(5-(naphthalen-2 yl)-1,3-phenylene)dianthracene (beta-AA) and 3,3',5,5'-tetra(naphthalen-1-yl) 1,1'-biphenyl (alpha,alpha,alpha,alpha-TNBP). The design of molecules was based on increasing molecular weight with varied pi-pi interactions in one or more substituents. The synthesis is based on Suzuki cross-coupling of 1-bromo-3-chloro 5-iodobenzene with arylboronic acids, which allows attachment of various substituents to tailor the chemical structure. The bulk compounds were characterized using NMR spectroscopy and differential scanning calorimetry (DSC). Thin films of these compounds were produced using physical vapor deposition and were subsequently annealed above the glass transition temperatures (Tg). For each molecular glass, cooling rate-dependent glass transition temperature measurements (CR-Tg) were performed using ellipsometry as a high-throughput method to characterize thin film properties. CR-Tg allows rapid characterization of glassy properties, such as Tg, apparent thermal expansion coefficients, apparent activation energy at Tg and fragility. DSC measurements confirmed the general trend that increasing molecular weight leads to increasing melting point (Tm) and Tg. Furthermore, CR-Tg provided evidence that the introduction of stronger pi interacting substituents in the chosen set of structural analogues increases fragility and decreases the ability to form glasses, such that beta-AA has the largest fragility and highest tendency to crystallize among all the compounds. These strong interactions also significantly elevate Tg and promote more harmonic intermolecular potentials, as observed by decreasing value of the apparent thermal expansion coefficient. PMID- 26280738 TI - Pt(II)-Catalyzed photosynthesis for H2 evolution cycling between singly and triply reduced species. AB - A PtCl2(bpy) derivative tethered to two viologen (MV(2+)) moieties drives photochemical H2 evolution via forming a three-electron-reduced species possessing a bpy(-)-based (or MV(0)-based) reducing equivalent. Such species can only form after one electron reduction of both the MV(2+) sites because of rapid intramolecular electron transfer from bpy(-) to MV(2+). PMID- 26280739 TI - Kaempferol Isolated from Nelumbo nucifera Inhibits Lipid Accumulation and Increases Fatty Acid Oxidation Signaling in Adipocytes. AB - Stamens of Nelumbo nucifera Gaertn have been used as a Chinese medicine due to its antioxidant, hypoglycemic, and antiatherogenic activity. However, the effects of kaempferol, a main component of N. nucifera, on obesity are not fully understood. We examined the effect of kaempferol on adipogenesis and fatty acid oxidation signaling pathways in 3T3-L1 adipocytes. Kaempferol reduced cytoplasmic triglyceride (TG) accumulation in dose and time-dependent manners during adipocyte differentiation. Accumulation of TG was rapidly reversed by retrieving kaempferol treatment. Kaempferol broadly decreased mRNA or protein levels of adipogenic transcription factors and their target genes related to lipid accumulation. Kaempferol also suppressed glucose uptake and glucose transporter GLUT4 mRNA expression in adipocytes. Furthermore, protein docking simulation suggests that Kaempferol can directly bind to and activate peroxisome proliferator-activated receptor (PPAR)-alpha by forming hydrophobic interactions with VAL324, THR279, and LEU321 residues of PPARalpha. The binding affinity was higher than a well-known PPARalpha agonist fenofibrate. Consistently, mRNA expression levels of PPARalpha target genes were increased. Our study indicates while kaempferol inhibits lipogenic transcription factors and lipid accumulation, it may bind to PPARalpha and stimulate fatty acid oxidation signaling in adipocytes. PMID- 26280740 TI - Evaluating the socioeconomic and cultural factors associated with pediatric burn injuries in Maputo, Mozambique. AB - BACKGROUND: Pediatric burn injuries are one of the leading causes of preventable morbidity and mortality in Sub-Saharan Africa. Research on the complex system of social, economic and cultural factors contributing to burn injuries in this setting is much needed. METHODS: We conducted a prospective questionnaire-based analysis of pediatric burn patients presenting to the Hospital Central de Maputo. A total of 39 patients were included in the study. Interviews were conducted with the children's caretakers by two trained medical students at the Eduardo Mondlane Medical School in Maputo with the aid of local nursing staff. RESULTS: Most burns occurred from scald wounds (26/39) particularly from bathwater, followed by fire burns (11/39). Burns occurred more frequently in the afternoon (16/39) and evening (16/39). Over one quarter of burns (9/33) occurred in the absence of a caretaker. One-third (12/36) of participants attempted to treat the burn at home prior to bringing the child into the hospital, and roughly two-thirds (24/37) reported using traditional remedies for burn care. The average household had just 2 rooms for an average of 5 family members. Most burns were second degree (25/37). CONCLUSIONS: Prevention efforts in this setting are much needed and can be implemented taking complex cultural and social factors into account. Education regarding regulation of water temperature for baths is important, given the prevalence of scald burns. Moreover, the introduction of low-cost, safer cooking technology can help mitigate inhalation injury and reduce fire burns. Additionally, burn care systems must be integrated with local traditional medical interventions to respect local cultural medicinal practices. PMID- 26280742 TI - Effectiveness of short-term endoscopic surgical skill training for young pediatric surgeons: a validation study using the laparoscopic fundoplication simulator. AB - PURPOSE: Pediatric surgeons require highly advanced skills when performing endoscopic surgery; however, their experience is often limited in comparison to general surgeons. The aim of this study was to evaluate the effectiveness of endoscopic surgery training for less-experienced pediatric surgeons and then compare their skills before and after training. METHODS: Young pediatric surgeons (n = 7) who participated in this study underwent a 2-day endoscopic skill training program, consisting of lectures, box training and live tissue training. The trainees performed the Nissen construction tasks before and after training using our objective evaluation system. A statistical analysis was conducted using the two-tailed paired Student's t tests. RESULTS: The time for task was 984 +/- 220 s before training and 645 +/- 92.8 s after training (p < 0.05). The total path length of both forceps was 37855 +/- 10586 mm before training and 22582 +/- 3045 mm after training (p < 0.05). The average velocity of both forceps was 26.1 +/- 3.68 mm/s before training and 22.9 +/- 2.47 mm/sec after training (p < 0.1). The right and left balance of suturing was improved after training (p < 0.05). CONCLUSION: Pediatric surgery trainees improved their surgical skills after receiving short-term training. We demonstrated the effectiveness of our training program, which utilized a new laparoscopic fundoplication simulator. PMID- 26280741 TI - Surgical approaches for neonatal congenital diaphragmatic hernia: a systematic review and meta-analysis. AB - PURPOSE: The optimal surgical approach for neonatal congenital diaphragmatic hernia (CDH) remains unclear. We conducted a systematic review and meta-analysis of the effectiveness of endoscopic surgery (ES) for neonatal CDH. METHODS: A systematic literature search was conducted using MEDLINE and the Cochrane Library. Studies that compared surgical approaches for neonatal CDH were selected. Mortality and recurrence of herniation were analyzed as primary endpoints. Each study was evaluated following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: Eight observational studies comparing ES and open surgery (OS) met the criteria. As compared with the OS group, the ES group showed both a significantly lower mortality rate [risk ratio (RR) 0.18, 95 % confidence interval (CI) 0.09-0.38, p < 0.0001] and a significantly higher recurrence rate (RR 3.10, 95 % CI 1.95-4.88, p < 0.00001). However, serious selection bias was seen in seven of the eight studies-because the indication of ES had been determined intentionally, the ES groups may have included less severe cases. CONCLUSION: Although the evidence was insufficient, ES was clearly associated with more recurrence than was OS. Therefore, ES should not be the routine treatment for every neonate. It is crucially important to select suitable cases for ES. PMID- 26280743 TI - Extraosseous Ewing sarcoma in the mesentery: the first report of cases in children. AB - Extraosseous ewing sarcoma (EES) is a rare soft-tissue tumor usually found in the extremities or paraspinal region. We describe the case of a 4-year-old boy with a large cystic mass in the mesentery diagnosed as mesenteric lymphangioma preoperatively and as EES after partial resection and histopathological examination. EES in the mesentery is extremely rare, with only 2 reports described in the English literature. This represents the first report of EES in a child. PMID- 26280744 TI - Specific effects in microwave chemistry explored through reactor vessel design, theory, and spectroscopy. AB - Microwave chemistry has revolutionized synthetic methodology for the preparation of organics, pharmaceuticals, materials, and peptides. The enhanced reaction rates commonly observed in a microwave have led to wide speculation about the function of molecular microwave absorption and whether the absorption leads to microwave specific effects and enhanced molecular heating. The comparison of theoretical modeling, reactor vessel design, and dielectric spectroscopy allows the nuance of the interaction to be directly understood. The study clearly shows an unaltered silicon carbide vessel allows measurable microwave penetration and therefore, molecular absorption of the microwave photons by the reactants within the reaction vessel cannot be ignored when discussing the role of molecular heating in enhanced molecular reactivity for microwave synthesis. The results of the study yield an improved microwave reactor vessel design that eliminates microwave leakage into the reaction volume by incorporating a noble metal surface layer onto a silicon carbide reaction vessel. The systematic study provides the necessary theory and measurements to better inform the arguments in the field. PMID- 26280745 TI - Assembly of Active Bacterial and Fungal Communities Along a Natural Environmental Gradient. AB - Dormancy is thought to promote biodiversity within microbial communities, but how assembly of the active community responds to changes in environmental conditions is unclear. To measure the active and dormant communities of bacteria and fungi colonizing decomposing litter in maple forests, we targeted ribosomal genes and transcripts across a natural environmental gradient. Within bacterial and fungal communities, the active and dormant communities were phylogenetically distinct, but patterns of phylogenetic clustering varied. For bacteria, active communities were significantly more clustered than dormant communities, while the reverse was found for fungi. The proportion of operational taxonomic units (OTUs) classified as active and the degree of phylogenetic clustering of the active bacterial communities declined with increasing pH and decreasing C/N. No significant correlations were found for the fungal community. The opposing pattern of phylogenetic clustering in dormant and active communities and the differential response of active communities to environmental gradients suggest that dormancy differentially structures bacterial and fungal communities. PMID- 26280746 TI - The Diversity and Co-occurrence Patterns of N2-Fixing Communities in a CO2 Enriched Grassland Ecosystem. AB - Diazotrophs are the major organismal group responsible for atmospheric nitrogen (N2) fixation in natural ecosystems. The extensive diversity and structure of N2 fixing communities in grassland ecosystems and their responses to increasing atmospheric CO2 remain to be further explored. Through pyrosequencing of nifH gene amplicons and extraction of nifH genes from shotgun metagenomes, coupled with co-occurrence ecological network analysis approaches, we comprehensively analyzed the diazotrophic community in a grassland ecosystem exposed to elevated CO2 (eCO2) for 12 years. Long-term eCO2 increased the abundance of nifH genes but did not change the overall nifH diversity and diazotrophic community structure. Taxonomic and phylogenetic analysis of amplified nifH sequences suggested a high diversity of nifH genes in the soil ecosystem, the majority belonging to nifH clusters I and II. Co-occurrence ecological network analysis identified different co-occurrence patterns for different groups of diazotrophs, such as Azospirillum/Actinobacteria, Mesorhizobium/Conexibacter, and Bradyrhizobium/Acidobacteria. This indicated a potential attraction of non-N2 fixers by diazotrophs in the soil ecosystem. Interestingly, more complex co occurrence patterns were found for free-living diazotrophs than commonly known symbiotic diazotrophs, which is consistent with the physical isolation nature of symbiotic diazotrophs from the environment by root nodules. The study provides novel insights into our understanding of the microbial ecology of soil diazotrophs in natural ecosystems. PMID- 26280747 TI - A population-based study on the associations between chronic periodontitis and the risk of cancer. AB - BACKGROUND: To date, the associations between chronic periodontitis (CP) and cancer lack large-scale population-based epidemiological evidence. This study aimed to investigate the subsequent risk for cancers among subjects with CP. METHODS: This study cohort included 40,140 subjects with CP and 40,140 subjects who were matched for a comparison cohort. We individually tracked each patient for a 5-year period following their index date to identify those who had received a diagnosis of cancer. RESULTS: The incidence rate of cancer during the 5-year follow-up period was 14.80 (95 % CI 14.28-15.34) per 1,000 person-years in subjects with CP. Cox proportional hazards regression revealed that the hazard ratio of cancer during the 5-year follow-up period for subjects with CP was 1.23 (95 % CI 1.20-1.27) compared to that of the comparison cohort. CONCLUSION: We observed an increased risk for the subsequent development of a number of cancers among subjects with CP. PMID- 26280748 TI - Growth rate of chemotherapy-naive lung metastasis from colorectal cancer could be a predictor of early relapse after lung resection. AB - PURPOSE: The aim of this study was to elucidate a potential risk factor for early relapse after pulmonary metastasectomy of colorectal cancer and to propose an optimal treatment strategy for lung metastasis with an aggressive nature. METHODS: Seventy patients who underwent pulmonary metastasectomy for diachronically measurable pulmonary lesions were retrospectively analyzed. We calculated the tumor doubling time (TDT) as the growth rate of lung metastasis and divided the study population into two groups: Rapid (TDT <= 100 days) and Slow (TDT > 100 days). RESULTS: The patients consisted of 47 males and 23 females, with a mean age of 63 years. Forty-two patients had a relapse after pulmonary metastasectomy with a median follow-up duration of 24 months. There was a significant difference in relapse-free survival between the Rapid and Slow groups (p = 0.047). Using a multivariate analysis, no preoperative chemotherapy and a high level of serum carcinoembryonic antigen were proven to be significant risk factors for relapse after metastasectomy. Meanwhile, multivariate analyses among 37 patients without preoperative chemotherapy indicated that TDT was the sole significant factor for relapse-free survival. In addition, eight of nine patients with relapse within 12 months were placed into the Rapid group. CONCLUSIONS: Although this was a preliminary study with a small number of patients, it suggested that lung metastases demonstrating a TDT of 100 days or less have a high risk of early relapse after metastasectomy. PMID- 26280749 TI - Influencing Factor Investigation on Dynamic Hydrothermal Growth of Gapped Hollow BaTiO3 Nanospheres. AB - Gapped hollow BaTiO3 nanospheres with an apparent diameter of 93 +/- 19 nm (shell thickness of 10-20 nm) were synthesized via a dynamic hydrothermal process using TiO2 sols and Ba(2+) ions as the Ti and Ba sources in alkaline aqueous solutions. The phases and morphologies of the BaTiO3 samples were characterized by X-ray diffraction (XRD), SEM, TEM, and Raman spectra. The effects of the hydrothermal temperatures and durations, NaOH concentrations, and Ba/Ti ratios on the formation of gapped hollow BaTiO3 nanospheres were systematically investigated. The optimum conditions for forming gapped hollow BaTiO3 nanospheres are hydrothermal treatment at 180 degrees C for 10-20 h under a continuous magnetic stirring with NaOH concentrations of about 1 mol/L and molar Ba/Ti ratios of 1.2 1.5. The formation mechanism of the gapped hollow BaTiO3 nanospheres is understood as the combination of the orientated attachment and reversed crystal growth. PMID- 26280750 TI - Disorder to Order Transition and Ordered Morphology of Coil-Comb Block Copolymer by Self-Consistent Field Theory. AB - The disorder to order transition and the ordered patterns near the disordered state of coil-comb copolymer A-b-(B m + 1-g-C m ) are investigated by the self consistent field theory. The phase diagrams of coil-comb copolymer are obtained by varying the composition of the copolymer with the side chain number m = 1, 2, and 3. The disorder to order transition is far more complex compared with the comb copolymer or linear block copolymer. As the side chain number m increases, the Flory-Huggins interaction parameter of disorder to order transition (DOT) increases and the lowest DOT occurs when the volume fractions of blocks A, B, and C are approximately equal. When one component is the minority, the disorder to order transition curve is similar with binary copolymer, but the curve shows the asymmetric property. The comb copolymer is more stable with larger side chain number m and shorter side chain. The ordered patterns from the disordered state are discussed. The results are helpful for designing coil-comb copolymers and obtaining the ordered morphology. PMID- 26280752 TI - Wearable and Implantable Mechanical Energy Harvesters for Self-Powered Biomedical Systems. AB - In this issue of ACS Nano, Tang et al. investigate the ability of a triboelectric nanogenerator (TENG) to self-power a low-level laser cure system for osteogenesis by studying the efficiency of a bone remodeling laser treatment that is powered by a skin-patch-like TENG instead of a battery. We outline this field by highlighting the motivations for self-powered biomedical systems and by discussing recent progress in nanogenerators. We note the overlap between biomedical devices and TENGs and their dawning synergy, and we highlight key prospects for future developments. Biomedical systems should be more autonomous. This advance could improve their body integration and fields of action, leading to new medical diagnostics and treatments. However, future self-powered biomedical systems will need to be more flexible, biocompatible, and biodegradable. These advances hold the promise of enabling new smart autonomous biomedical systems and contributing significantly to the Internet of Things. PMID- 26280751 TI - Structural Image Analysis of the Brain in Neuropsychology Using Magnetic Resonance Imaging (MRI) Techniques. AB - Magnetic resonance imaging (MRI) of the brain provides exceptional image quality for visualization and neuroanatomical classification of brain structure. A variety of image analysis techniques provide both qualitative as well as quantitative methods to relate brain structure with neuropsychological outcome and are reviewed herein. Of particular importance are more automated methods that permit analysis of a broad spectrum of anatomical measures including volume, thickness and shape. The challenge for neuropsychology is which metric to use, for which disorder and the timing of when image analysis methods are applied to assess brain structure and pathology. A basic overview is provided as to the anatomical and pathoanatomical relations of different MRI sequences in assessing normal and abnormal findings. Some interpretive guidelines are offered including factors related to similarity and symmetry of typical brain development along with size-normalcy features of brain anatomy related to function. The review concludes with a detailed example of various quantitative techniques applied to analyzing brain structure for neuropsychological outcome studies in traumatic brain injury. PMID- 26280753 TI - Shear bond strength of different types of adhesive systems to dentin and enamel of deciduous teeth in vitro. AB - OBJECTIVES: The present study aimed to evaluate the suitability of self-etch adhesives for restoration of deciduous teeth compared with etch and rinse approaches. MATERIALS AND METHODS: One hundred twenty primary teeth were divided into five groups, each being assigned to an adhesive system. Self-etch adhesives XenoV (XV) and Clearfil S(3) Bond (CB), Prime&Bond NT with (PBE)/without preliminary etching (PBN), and Optibond FL (OBFL) as an etch and rinse system were included. Enamel and dentin specimens were prepared (n = 36/group), adhesives applied, and compomer cylinders polymerized. After 24-h storage in 37 degrees C distilled water and thermo-cycling (1440 cycles, 5/55 degrees C, 27 s), shear bond tests and fracture mode classification based on SEM investigation were performed. Statistical analysis involved ANOVA and Scheffe procedure with Bonferroni-Holm correction (p <= 0.005). RESULTS: High shear bond strengths to primary enamel were determined for PBE (mean [M] = 22.48 +/- 7.7 MPa) > OBFL (M = 19.06 +/- 5.62 MPa) > CB (M = 17.6 +/- 6.55 MPa), and XV (M = 16.85 +/- 5.38 MPa) and PBN (M = 8.26 +/- 4.46 MPa) formed significantly less reliable enamel-resin interfaces (p <= 0.005). PBE generated the highest bond strength on primary dentin (M = 21.97 +/- 8.02 MPa); significantly lower values were measured for XV (M = 13.44 +/- 5.43 MPa) and OBFL (M = 12.92 +/- 4.31 MPa) (p <= 0.005). CONCLUSIONS: Adhesives requiring preliminary etching ensure optimal bond strength to primary enamel. If separate etching is to be avoided, selected self-etch adhesives obtain acceptable shear bond values on primary enamel and dentin. CLINICAL RELEVANCE: The treatment of pediatric patients presents a great challenge in dental practice, and optimization of treatment processes is important. PMID- 26280754 TI - Deliberative and intuitive risk perceptions as predictors of colorectal cancer screening over time. AB - Cancer risk perceptions may involve intuitions-including both affect as well as gut-level thoughts about risk-and deliberative risk magnitudes. Yet, little research has examined the potentially diverse relations between risk perceptions and behavior across time. A highly diverse primary care sample (N = 544, aged >=50) was utilized to compare how deliberative and intuitive perceptions of risk relate to chart-confirmed colorectal cancer screening at cross-sectional and prospective time points. At baseline, deliberative and intuitive risk perceptions were negatively associated with chart-confirmed colorectal cancer screening adherence in bivariable but not multivariable analyses. Among those who were non adherent with colorectal cancer screening at baseline, deliberative and intuitive risk perceptions were positively associated with prospective uptake of chart confirmed colorectal cancer screening adherence at 12-months in bivariable analyses; only deliberative risk perceptions remained significant in the multivariable model. This study indicates that diverse risk perceptions are differentially important for screening at different time points. PMID- 26280756 TI - Pharmacokinetics, Pharmacodynamics, and Safety of Canagliflozin in Japanese Patients with Type 2 Diabetes Mellitus. AB - INTRODUCTION: Canagliflozin is a sodium glucose co-transporter 2 inhibitor approved worldwide for the treatment of patients with type 2 diabetes mellitus (T2DM). The present study evaluated pharmacokinetics, pharmacodynamics, and safety of canagliflozin in Japanese patients with T2DM. METHODS: Canagliflozin, at doses of 25, 100, 200, or 400 mg, was administered as a single dose and, after a washout of 1 day, in repeated doses for 14 consecutive days to 61 subjects in a randomized, double-blind, placebo-controlled study. Plasma concentrations of canagliflozin and urinary glucose excretion (UGE) were measured, and renal threshold for glucose excretion (RTG) was calculated. Safety was evaluated on the basis of adverse event (AE) reports, blood and urine laboratory parameters, and vital signs. RESULTS: Plasma canagliflozin maximum concentration and area under the concentration-time curve (AUC) values increased in a dose-dependent manner with the time to maximum concentration (t max) of 1.0 h and elimination half-life (t 1/2) of 10.22-13.26 h on Day 1. No significant changes in t max and t 1/2 were observed after multiple-dose administration. The linearity factors, as calculated from the ratios of AUC0-24h on Day 16 to AUC0-infinity on Day 1, were close to 1 in all canagliflozin groups. Canagliflozin increased UGE0-24h (80-110 g/day with canagliflozin >=100 mg) and decreased RTG from the first day of treatment; these effects were sustained during the entire period of multiple administration. No significant AEs were noted. Urine volume was slightly increased on Day 1, but subsequent changes after repeated doses for 14 days were small. Urinary sodium tended to be higher in the early treatment period, whereas no particular change was observed in serum osmolality and hematocrit. CONCLUSION: Canagliflozin increased UGE, decreased RTG, and was well tolerated throughout the entire period of multiple administrations in Japanese patients with T2DM. FUNDING: Mitsubishi Tanabe Pharma Corporation. TRIAL REGISTRATION: ClinicalTrials.gov#NCT00707954. PMID- 26280755 TI - Does colorectal cancer risk perception predict screening behavior? A systematic review and meta-analysis. AB - Although health behavior theories postulate that risk perception should motivate colorectal cancer (CRC) screening, this relationship is unclear. This meta analysis aims to examine the relationship between CRC risk perception and screening behavior, while considering potential moderators and study quality. A search of six databases yielded 58 studies (63 effect sizes) that quantitatively assessed the relationship between CRC risk perception and screening behavior. Most included effect sizes (75 %) reported a positive association between CRC risk perception and screening behavior. A random effects meta-analysis yielded an overall effect size of z = 0.13 (95 % CI 0.10-0.16), which was heterogeneous (I (2) = 99 %, tau(2) = 0.01). Effect sizes from high-quality studies were significantly lower than those from lower quality studies (z = 0.02 vs. 0.16). We found a small, positive relationship between CRC risk perception and reported screening behavior, with important identified heterogeneity across moderators. Future studies should focus on high quality study design. PMID- 26280757 TI - Progress in Alkaptonuria--are we near to an effective therapy? PMID- 26280758 TI - Generation and the subjective feeling of "aha!" are independently related to learning from insight. AB - It has been proposed that sudden insight into the solutions of problems can enhance long-term memory for those solutions. However, the nature of insight has been operationalized differently across studies. Here, we examined two main aspects of insight problem-solving-the generation of a solution and the subjective "aha!" experience-and experimentally evaluated their respective relationships to long-term memory formation (encoding). Our results suggest that generation (generated solution vs. presented solution) and the "aha!" experience ("aha!" vs. no "aha!") are independently related to learning from insight, as well as to the emotional response towards understanding the solution during encoding. Moreover, we analyzed the relationship between generation and the "aha!" experience and two different kinds of later memory tests, direct (intentional) and indirect (incidental). Here, we found that the generation effect was larger for indirect testing, reflecting more automatic retrieval processes, while the relationship with the occurrence of an "aha!" experience was somewhat larger for direct testing. Our results suggest that both the generation of a solution and the subjective experience of "aha!" indicate processes that benefit long-term memory formation, though differently. This beneficial effect is possibly due to the intrinsic reward associated with sudden comprehension and the detection of schema-consistency, i.e., that novel information can be easily integrated into existing knowledge. PMID- 26280759 TI - Risk of Cardiovascular Implantable Electronic Device Malfunction With Radiation Therapy: Location, Dose, or Energy? PMID- 26280761 TI - Molecular Response Theory in Terms of the Uncertainty Principle. AB - We investigate the time response of molecular transitions by observing the pulse reshaping of femtosecond THz-pulses propagating through polar vapors. By precisely modeling the pulse interaction with the molecular vapors, we derive detailed insight into this time response after an excitation. The measurements, which were performed by applying the powerful technique of THz time domain spectroscopy, are analyzed directly in the time domain or parallel in the frequency domain by Fourier transforming the pulses and comparing them with the molecular response theory. New analyses of the molecular response allow a generalized unification of the basic collision and line-shape theories of Lorentz, van Vleck-Weisskopf, and Debye described by molecular response theory. In addition, they show that the applied THz experimental setup allows the direct observation of the ultimate time response of molecules to an external applied electric field in the presence of molecular collisions. This response is limited by the uncertainty principle and is determined by the inverse spitting frequency between adjacent levels. At the same time, this response reflects the transition time of a rotational transition to switch from one molecular state to another or to form a coherent superposition of states oscillating with the splitting frequency. The presented investigations are also of fundamental importance for the description of the far-wing absorption of greenhouse gases like water vapor, carbon dioxide, or methane, which have a dominant influence on the radiative exchange in the far-infrared. PMID- 26280760 TI - GABAergic mechanisms regulated by miR-33 encode state-dependent fear. AB - Fear-inducing memories can be state dependent, meaning that they can best be retrieved if the brain states at encoding and retrieval are similar. Restricted access to such memories can present a risk for psychiatric disorders and hamper their treatment. To better understand the mechanisms underlying state-dependent fear, we used a mouse model of contextual fear conditioning. We found that heightened activity of hippocampal extrasynaptic GABAA receptors, believed to impair fear and memory, actually enabled their state-dependent encoding and retrieval. This effect required protein kinase C-betaII and was influenced by miR 33, a microRNA that regulates several GABA-related proteins. In the extended hippocampal circuit, extrasynaptic GABAA receptors promoted subcortical, but impaired cortical, activation during memory encoding of context fear. Moreover, suppression of retrosplenial cortical activity, which normally impairs retrieval, had an enhancing effect on the retrieval of state-dependent fear. These mechanisms can serve as treatment targets for managing access to state-dependent memories of stressful experiences. PMID- 26280762 TI - Rational Design of Glycomimetic Compounds Targeting the Saccharomyces cerevisiae Transglycosylase Gas2. AB - The transglycosylase Saccharomyces cerevisiae Gas2 (ScGas2) belongs to a large family of enzymes that are key players in yeast cell wall remodeling. Despite its biologic importance, no studies on the synthesis of substrate-based compounds as potential inhibitors have been reported. We have synthesized a series of docking guided glycomimetics that were evaluated by fluorescence spectroscopy and saturation-transfer difference (STD) NMR experiments, revealing that a minimum of three glucose units linked via a beta-(1,3) linkage are required for achieving molecular recognition at the binding donor site. The binding mode of our compounds is further supported by STD-NMR experiments using the active site mutants Y107Q and Y244Q. Our results are important for both understanding of ScGas2-substrate interactions and setting up the basis for future design of glycomimetics as new antifungal agents. PMID- 26280765 TI - The association between linoleic acid levels in colostrum and child cognition at 2 and 3 y in the EDEN cohort. PMID- 26280766 TI - Sterilization of rotary NiTi instruments within endodontic sponges. AB - AIM: To determine whether the following can be sterilized by autoclaving - endodontic sponges, rotary nickel-titanium (NiTi) instruments within endodontic sponges, and rotary NiTi instruments with rubber stoppers. METHODOLOGY: Sixty four samples of eight different endodontic sponges (n = 512) were placed into brain heart infusion broth (BHI) for 72 h. An aliquot of this was then spread onto horse blood agar and cultured aerobically and anaerobically to test sterility at purchase. Bacterial suspensions of Enterococcus faecalis, Porphyromonas gingivalis and Geobacillus stearothermophilus in BHI were used to contaminate sterile sponges and rotary NiTi instruments (with and without rubber stoppers) inserted into sponges. The various samples were autoclaved and then cultured aerobically and anaerobically. Success of sterilization was measured qualitatively as no growth. The experiment was repeated with clinically used rotary NiTi instruments (n = 512). All experiments were conducted in quadruplicate. RESULTS: No sponges on purchase had microbial growth when anaerobically cultured but some did when aerobically cultured. All autoclaved sponges and instruments (within or without sponges, and with or without rubber stoppers) were associated with no microbial growth. All nonautoclaved positive control samples showed microbial growth. CONCLUSIONS: Autoclaving was effective in the sterilization of sponges and endodontic instruments. Endodontic sponges should be autoclaved before clinical use. For clinical efficiency and cost effectiveness, rotary NiTi instruments can be sterilized in endodontic sponges without removal of rubber stoppers. PMID- 26280764 TI - Diagnostic screening for subclinical celiac disease using a rapid test in children aged 2-4. AB - BACKGROUND: Our aim is to study the prevalence of subclinical celiac disease (CD) and analyze the diagnostic yield of a new rapid test in children aged 2-4. METHODS: We carried out a cross-sectional study in a sample population of children aged 2-4 from the same metropolitan area. We recruited apparently healthy subjects, and collected clinical, anthropometric, analytical, and serological variables. We also tested for anti-gliadin IgA and anti transglutaminase IgG and IgA using a rapid immunochromatographic test CD1WB and CD2WB (Operon, Zaragoza, Spain). RESULTS: One hundred and ninety-eight children were recruited, signed the informed consent form, and completed the protocol (mean age 32.3 +/- 9.2 mo, 53% males). CD prevalence according to the serological tests was 3% (CI 95%, 1.4-6.4%). Biopsies were used to confirm the diagnosis in all suspected cases. The sensitivity and negative predictive value of the CD2WB immunochromatographic test strip were 100% and 1, respectively. The sensitivity of CD1WB was 16.6% and its specificity was high (89.1%). CONCLUSION: The prevalence of subclinical CD in the sample group of 2-4-y old was higher than that found by other authors. The CD2WB immunochromatographic test strip is an excellent diagnostic screening tool with high sensitivity and negative predictive value. PMID- 26280767 TI - Risk Stratification of Necrotizing Fasciitis Based on the Initial Procalcitonin Concentration: A Single Center Observational Study. AB - BACKGROUND: Necrotizing fasciitis (NF) is a potentially fatal subcutaneous tissue and fascia infection. We studied the role of serum procalcitonin in the identification and assessment of severity of sepsis in patients with NF. METHODS: A retrospective analysis was conducted from January 2000 to December 2013 for all patients who admitted to surgical intensive care with provisional diagnosis of NF. Patients were categorized into four groups based on the initial procalcitonin concentrations (Group I: <0.5 low risk, Group II: >=0.5-<2 moderate risk, Group III: >=2-<10 high risk, and Group IV: >=10 ng/mL high likelihood of severe sepsis). RESULTS: During the study period, 331 cases were identified to have NF with a mean age of 51 +/- 14 years. Serum procalcitonin was tested in 62 cases (only between 2011 and December 2013) and all were positive (Group I: 22%, Group II: 18%, Group III: 21%, and Group IV: 39%). The most common affected regions were thigh and chest in Group II (46% and 9%, respectively), lower limbs in Group III (46%), and perineum and abdomen in Group IV (25% and 21%, respectively). In the four groups, 21 patients developed septic shock (Group I: 0%, Group II: 14%, Group III: 24%, and Group IV: 62%). The cut off procalcitonin value for septic shock was 5.6 ng/mL. Using receiver-operating characteristic curve, this cut off with the Area under the Curve (AUC) of 0.77 was found to have sensitivity 81% and specificity 67%. Sequential Organ Failure Assessment (SOFA) score was substantially greater in Group III and Group IV in comparison to Group I and Group II, p = 0.006. Procalcitonin levels were correlated well with SOFA score (r = 0.34, p = 0.007). There were 17 deaths in the four groups (Group I: 6%, Group II: 23%, Group III: 12%, and Group IV: 59%). CONCLUSION: Initial procalcitonin concentration in NF carries an important prognostic value and it correlates well with SOFA score and can predict the development of septic shock early in patients with NF. PMID- 26280768 TI - Healthcare Professionals' Perceptions and Knowledge of the USPSTF Guidelines on Breast Self-Examination. AB - OBJECTIVES: In 2009, the US Preventive Services Task Force (USPSTF) published revised guidelines for breast cancer screening, which recommended against teaching breast self-examination (BSE). The objective of this study was to assess providers' perceptions and knowledge regarding these updated guidelines. METHODS: A cross-sectional survey study was administered to 205 attending and resident physicians, nurse practitioners, physician's assistants, and registered nurses working in five medical and gynecological practices affiliated with a large academic teaching hospital in western Massachusetts. The survey solicited demographic data and inquired about practitioners' perceptions and knowledge of the revised guidelines. RESULTS: Fewer than half (41.1%) of respondents correctly identified the new USPSTF guidelines for BSE. Among those who stated they were aware of guidelines, only 37.1% adhered to them. Overall, 70% report that they teach patients to perform BSE. Teaching BSE was associated with female sex (odds ratio [OR] 2.64, 95% confidence interval [CI] 1.11-6.29), a belief that BSE reduces morbidity and mortality (OR 2.91, 95% CI 1.08-7.81), and internal medicine residency (OR 0.18, 95% CI 0.06-0.59). CONCLUSIONS: Knowledge of the 2009 USPSTF guidelines is suboptimal and greater efforts should be made to educate healthcare professionals about them. PMID- 26280769 TI - Limited Uptake of Planned Intrauterine Devices During the Postpartum Period. AB - OBJECTIVES: The primary objective of this study was to determine the percentage of women with a documented plan for postpartum intrauterine device (IUD) insertion who had a device inserted within 8 weeks of delivery. The secondary objective was to determine factors associated with successful initiation of postpartum IUDs as planned. METHODS: We conducted a retrospective chart review of women who had at least one prenatal visit and delivered a viable pregnancy at our academic medical center. Methods of planned and established postpartum contraceptive methods were recorded, as well as demographic information and documented reasons for failure to initiate planned intrauterine contraception. RESULTS: A total of 110 women planned postpartum IUD placement. Of these women, 84 (76%) presented for at least one postpartum appointment. Only 22.6% (95% confidence interval 13.7-31.5) of those presenting for postpartum follow-up underwent IUD placement within 8 weeks of delivery. Women planning postpartum IUD insertion were just as likely as women with no planned postpartum contraceptive method to fail to establish contraception within 8 weeks (P = 0.55). CONCLUSIONS: Failure to establish planned postpartum intrauterine contraception occurs frequently, even in a setting with a high rate of postpartum follow-up. PMID- 26280770 TI - Commentary on "Limited Uptake of Planned Intrauterine Devices During the Postpartum Period". PMID- 26280771 TI - Empathy, Sense of Power, and Personality: Do They Change During Pediatric Residency? AB - OBJECTIVES: Empathy is a critical competency in medicine. Prior studies demonstrate a longitudinal decrease in empathy during residency; however, they have not included pediatric residents. The relations among the expression of empathy, sense of power (ability to influence other's behavior), and personality traits in residents also have not been addressed. Lastly, there are no data on how residents compare with the general nonmedical population in their expression of empathy. The purposes of our study were to assess whether empathy, sense of power, and personality type were statistically correlated; if resident empathy declines over time; and how resident empathy compares with that of nonmedical peers. METHODS: In 2010, a cohort of individuals entering pediatric residency were given three validated survey instruments at the beginning of their first and third years of training to explore longitudinal changes in empathy, sense of power, and major personality traits. RESULTS: We found no decrease in resident empathy in 2 years of pediatric training, no changes in their sense of power, and no statistically significant correlation between empathetic tendencies and sense of power. When compared with the general nonmedical population, pediatric residents rated themselves higher in empathy. As expected, the two components of empathy (empathic concern and perspective taking) were moderately correlated. Of the major personality traits, only agreeableness showed significant correlation with empathy. CONCLUSIONS: Pediatric resident empathy did not decrease longitudinally, unlike studies in other residents. There was no inverse relation between self-perceptions of sense of power and empathy as is present in the business literature. Finally, pediatric resident empathy was significantly higher when compared with a general nonmedical population. PMID- 26280772 TI - Commentary on "Empathy, Sense of Power, and Personality: Do They Change During Pediatric Residency?". PMID- 26280774 TI - Being Cultured While Culturing. PMID- 26280773 TI - Number of General Medicine Hospital Admissions Performed by Internal Medicine Residents Before and After the 2011 Duty-Hour Regulations. AB - OBJECTIVES: In July 2011 the Accreditation Council for Graduate Medical Education implemented new resident duty-hour regulations in an effort to improve resident well-being, clinical performance, and patient care. These regulations have the potential, however, to reduce the number of new patient encounters handled by trainees and thereby could be detrimental to resident education. Our objective was to describe how the 2011 duty-hour regulations affected the volume of new inpatient general medicine encounters at two large academic medical centers. We looked specifically at new patient encounters because we assumed they provided the richest learning opportunities. We hypothesized that the implementation of the Accreditation Council for Graduate Medical Education regulations would be associated with a reduction in the number of new admissions per day and result in a decrease in the number of annual admissions performed by first-year medical residents. METHODS: We conducted a retrospective ecological study. We reviewed general medicine admissions data from two large academic hospitals affiliated with the University of Washington: Harborview Medical Center and the University of Washington Medical Center. We abstracted the number of admissions, source of admission, and average intern census on 56 randomly selected days before and after the regulations were implemented (academic years 2010-2011 [AY11] and 2011 2012 [AY12]). We generated descriptive statistics (means, proportions, and 95% confidence intervals) and then used a two-sample t test to compare the number of admissions per day, admission source, and average daily intern census between AY11 and AY12. RESULTS: At the University of Washington Medical Center, single intern teams admitted 4.5 patients per day in AY11 compared with 3.1 in AY12 (P < 0.001). At Harborview Medical Center, two-intern teams admitted 11.1 patients per day in AY11 versus 7.9 in AY12 (P < 0.001). Night interns admitted 0.9 patients per shift in AY11 versus 2.4 in AY12 (P < 0.001). After implementing the new duty hours, daytime admissions from the emergency department decreased and admissions as transfers from the intensive care unit increased. The average intern census was not affected by the duty-hour regulations. CONCLUSIONS: Medicine residents admit fewer patients on daytime inpatient general medicine services under the new duty-hour regulations; however, this is completely offset by an increase in the number of admissions performed on the night rotation, resulting in no net change in the total number of new inpatient encounters handled by first-year medical residents during the course of the academic year. Although this is reassuring, changes that were made in response to the work-hour rules have altered how new admissions are distributed to teams, which has important implications for curricular design and supervision. PMID- 26280776 TI - Commentary on "Updated Prevalence and Demographic Characteristics for ALS Cases in Texas, 2009-2011". PMID- 26280775 TI - Updated Prevalence and Demographic Characteristics for ALS Cases in Texas, 2009 2011. AB - OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a rare motor neuron disease with incidence rates ranging from 1 to 2/100,000 person-years. The Texas Department of State Health Services previously conducted surveillance for ALS in three metropolitan areas of Texas. This project provides an update to this research, while expanding its scope to the entire state. METHODS: The Texas Department of State Health Services contacted neurologists throughout Texas to determine whether they diagnose or treat patients with ALS. Those neurologists who cared for Texas residents with ALS between 2009 and 2011 were asked to complete a one-page case reporting form for each patient. RESULTS: A total of 1422 unique cases were received. The average crude annual incidence rate was 1.30/100,000 person-years and the 2009 period prevalence rate was 2.92/100,000 individuals. Reported cases were most likely to be 60 to 69 years old, non Hispanic, white, and men. CONCLUSIONS: This project provides an update to previously published Texas-specific epidemiological data regarding ALS; also, we note that our findings are consistent with previously published studies. PMID- 26280778 TI - Commentary on "Understanding the Health Needs and Barriers to Seeking Health Care of Veteran Students in the Community". PMID- 26280777 TI - Understanding the Health Needs and Barriers to Seeking Health Care of Veteran Students in the Community. AB - OBJECTIVES: Access to care at Veterans Affairs facilities may be limited by long wait times; however, additional barriers may prevent US military veterans from seeking help at all. We sought to understand the health needs of veterans in the community to identify possible barriers to health-seeking behavior. METHODS: Focus groups were conducted with veteran students at a community college until thematic saturation was reached. Qualitative data analysis involved both an inductive content analysis approach and deductive elements. RESULTS: A total of 17 veteran students participated in 6 separate focus groups. Health needs affecting health-seeking behavior were identified. Themes included lack of motivation to improve health, concern about social exclusion and stigma, social interactions and behavior, limited access to affordable and convenient health care, unmet basic needs for self and family, and academics competing with health needs. CONCLUSIONS: Veterans face a range of personal, societal, and logistical barriers to accessing care. In addition to decreasing wait times for appointments, efforts to improve the transition to civilian life; reduce stigma; and offer assistance related to work, housing, and convenient access to health care may improve health in veteran students. PMID- 26280779 TI - Comportment and Communication Patterns among Hospitalist Physicians: Insight Gleaned Through Observation. AB - OBJECTIVES: By 2014, there were more than 40,000 hospitalists delivering the majority of inpatient care in US hospitals. No empiric research has characterized hospitalist comportment and communication patterns as they care for patients. METHODS: The chiefs of hospital medicine at five different hospitals were asked to identify their best hospitalists. These hospitalists were watched during their routine clinical care of patients. An observation tool was developed that focused on elements believed to be associated with excellent comportment and communication. One observer watched the physicians, taking detailed quantitative and qualitative field notes. RESULTS: A total of 26 hospitalists were shadowed. The mean age of the physicians was 38 years, and their average experience in hospital medicine was 6 years. The hospitalists were observed for a mean of 5 hours, during which time they saw an average of 7 patients (patient encounters observed N = 181). Physicians spent an average of 11 minutes with each patient. There was large variation in the extent to which desirable behaviors were performed. For example, most physicians (76%) started encounters with an open ended question, and relatively few (30%) attempted to integrate nonmedical content into conversation with patients. CONCLUSIONS: This study represents a first step in trying to characterize comportment and communication in hospital medicine. Because hospitalists spend only a small proportion of their clinical time in direct patient care, it is imperative that excellent comportment and communication are clearly defined and established as a goal for every encounter. PMID- 26280781 TI - Commentary on "Age-Related Macular Degeneration and Coronary Artery Disease in a VA Population". PMID- 26280780 TI - Age-Related Macular Degeneration and Coronary Artery Disease in a VA Population. AB - OBJECTIVES: Age-related macular degeneration (AMD) is the leading cause of blindness in the United States. Although AMD shares multiple risk factors with coronary artery disease (CAD), the association between AMD and CAD has not been established. The objective of our study was to demonstrate an association between the diagnosis of AMD and CAD and/or major cardiovascular risk factors. METHODS: We performed a retrospective chart review of >13,000 patients at the Lexington Veterans Affairs Medical Center. Patients diagnosed as having AMD served as cases, and patients diagnosed with cataract and no AMD served as controls. We examined the prevalence of CAD and associated risk factors in both groups using univariate analysis followed by multivariate analyses to examine the association between AMD and CAD after adjusting for known common risk factors. RESULTS: We identified 3950 patients with AMD and 9166 controls. Patients with AMD were on average 6 years older than controls (P < 0.001) and had a significantly higher prevalence of CAD (39% vs 34%) and hypertension (88% vs 83%) but lower incidence of diabetes mellitus and smoking. Estimated odds ratio relating CAD to AMD was 1.22 (95% confidence interval 1.13-1.32; P < 0.001). The association between CAD and AMD remained significant in multivariate analyses in older individuals (76 years and older). When we conducted a secondary analysis and matched the AMD and non-AMD groups based on age, the association between CAD and AMD remained significant (39.4% in the AMD group vs 36.6% in the non-AMD group; P = 0.011). CONCLUSIONS: These findings support the existence of an association between CAD and AMD, particularly in older adult patients in the predominantly male Veterans Affairs population. Such an association between AMD and systemic vascular disease justifies the potential coscreening for these conditions. PMID- 26280782 TI - Immunohistochemistry should undergo robust validation equivalent to that of molecular diagnostics. AB - Immunohistochemistry (IHC) is a widely available and highly utilised tool in diagnostic histopathology and is used to guide treatment options as well as provide prognostic information. IHC is subjected to qualitative and subjective assessment, which has been criticised for a lack of stringency, while PCR-based molecular diagnostic validations by comparison are regarded as very rigorous. It is essential that IHC tests are validated through evidence-based procedures. With the move to ISO15189 (2012), not just of the accuracy, specificity and reproducibility of each test need to be determined and managed, but also the degree of uncertainty and the delivery of such tests. The recent update to ISO 15189 (2012) states that it is appropriate to consider the potential uncertainty of measurement of the value obtained in the laboratory and how that may impact on prognostic or predictive thresholds. In order to highlight the problems surrounding IHC validity, we reviewed the measurement of Ki67and p53 in the literature. Both of these biomarkers have been incorporated into clinical care by pathology laboratories worldwide. The variation seen appears excessive even when measuring centrally stained slides from the same cases. We therefore propose in this paper to establish the basis on which IHC laboratories can bring the same level of robust validation seen in the molecular pathology laboratories and the principles applied to all routine IHC tests. PMID- 26280783 TI - Diagnostic accuracy of haemoglobin colour strip (HCS-HLL), a digital haemoglobinometer (TrueHb) and a non-invasive device (TouchHb) for screening patients with anaemia. AB - AIM: Estimation of haemoglobin (Hb) remains a challenge, particularly in outreach settings. There is a need to have a simple and cost-effective device to detect anaemia. Three devices (haemoglobin colour scale (HCS)-HLL (Hindustan Lifecare Limited), TrueHb V.1.1, TouchHb Alpha 1.1- non-invasive) have been developed in India recently. This study aimed to determine the diagnostic accuracy of these tests (index) for the screening of anaemia against haematological autoanalyzer (reference). METHODS: The study was conducted in four medical colleges of India. All consenting adult patients (>18 years of age) undergoing routine investigations were included. Each patient underwent the reference test and at least one index test. Outcome assessors for the index tests were blinded to the results of the reference test. Diagnostic accuracy was calculated using cut-offs proposed by WHO. RESULTS: A total of 5244 patients underwent the reference test while HCS-HLL, TrueHb and TouchHb tests were conducted on 2745, 2331 and 2874 patients respectively. The positive likelihood ratio of HCS-HLL using capillary blood (1.2), venous blood (1.7) and TouchHb (1.5) was lower than TrueHb capillary (3.7; 95% CI 3.3 to 4.2) and venous blood (5.7; 95% CI 4.9 to 6.6). TrueHb had a sensitivity of 74.4% (95% CI 71.9% to 76.8%) for venous and 82.0% (95% CI 79.8% to 89.2%) for capillary samples. The specificity was high (>75.0%). The area under receiver operating characteristic was close to 80.0%. Consistent results were seen for detection of severe anaemia. CONCLUSIONS: The digital method (TrueHb) emerged as a better diagnostic method for screening anaemia. Its effectiveness should be established in outreach settings before further recommendation. PMID- 26280784 TI - The Role of RAAS Inhibition by Aliskiren on Paracetamol-Induced Hepatotoxicity Model in Rats. AB - Paracetamol is one of the most popular and widely used analgesic and antipyretic agents, but an overdose can cause hepatotoxicity and lead to acute liver failure. Aliskiren directly inhibits renin which downregulates the renin-angiotensin aldosterone system (RAAS). Recent findings suggest that RAAS system takes part in the pathogenesis of liver fibrosis. We aimed to reveal the relationship between hepatotoxicity and the RAAS by examining paracetamol induced hepatotoxicity. Rats were separated into five groups as follows: control, 100 mg/kg aliskiren (p.o.), 2 g/kg paracetamol (per os (p.o.)), 2 g/kg paracetamol + 50mg/kg aliskiren (p.o.), and 2 g/kg paracetamol + 100 mg/kg aliskiren(p.o.). Samples were analyzed at the biochemical, molecular, and histopathological levels. Paracetamol toxicity increased alanine aminotransferases (ALT), aspartate aminotransferases (AST), renin, and angiotensin II levels in the serum samples. In addition, the SOD activity and glutathione (GSH) levels decreased while Lipid Peroxidation (MDA) levels increased in the livers of the rats treated with paracetamol. Paracetamol toxicity caused a significant increase in TNF-alpha and TGF-beta. Both aliskiren doses showed an improvement in ALT, AST, oxidative parameters, angiotensin II, and inflammatory cytokines. Only renin levels increased in aliskiren treatment groups due to its pharmacological effect. A histopathological examination of the liver showed that aliskiren administration ameliorated the paracetamol-induced liver damage. In immunohistochemical staining, the expression of TNF-alpha in the cytoplasm of the hepatocytes was increased in the paracetamol group but not in other treatment groups when compared to the control group. In light of these observations, we suggest that the therapeutic administration of aliskiren prevented oxidative stress and cytokine changes and also protected liver tissues during paracetamol toxicity by inhibiting the RAAS. PMID- 26280785 TI - Giant Rugby Ball [{Cp(Bn)Fe(eta(5)-P5)}24Cu96Br96] Derived from Pentaphosphaferrocene and CuBr2. AB - The self-assembly of [Cp(Bn)Fe(eta(5)-P5)] (Cp(Bn) = eta(5)-C5(CH2Ph)5) with CuBr2 leads to the formation of an unprecedented rugby ball-shaped supramolecule consisting of 24 units of the pentaphosphaferrocene and an extended CuBr framework, which does not follow the fullerene topology. The resulting scaffold of 312 noncarbon atoms reveals three different coordination modes of the cyclo-P5 ligand including a novel pi-coordination. The outer dimensions of 3.7 * 4.6 nm of the sphere approach the range of the size of proteins. With a value of 32.1 nm(3), it is 62 times larger in volume than a C60 molecule. Surprisingly, this giant rugby ball is also slightly soluble in CH2Cl2. PMID- 26280787 TI - Stronger Together. PMID- 26280786 TI - Ledipasvir/sofosbuvir treatment of hepatitis C virus is associated with reduction in serum apolipoprotein levels. AB - The interaction of lipoproteins with hepatitis C virus (HCV) has pathogenic and therapeutic implications. Our aim was to evaluate changes in the apolipoprotein profile of patients with chronic hepatitis C during and after successful cure with ledipasvir and sofosbuvir (LDV/SOF) with and without ribavirin (RBV). One hundred HCV genotype 1 patients who had achieved SVR-12 after treatment with 12 weeks of LDV/SOF +/- RBV were selected from the ION-1 clinical trial. Frozen serum samples from baseline, end of treatment and week 4 of follow-up were used to assay apolipoproteins (apoAI, apoAII, apoB, apoCII, apoCIII, apoE) using the Multiplex platform to assess for changes in the apolipoprotein levels. At the end of treatment compared to baseline, a significant reduction in apoAII levels ( 14.97 +/- 63.44 MUg/mL, P = 0.0067) and apoE levels (-4.38 +/- 12.19 MUg/mL, P < 0.001) was noted. These declines from baseline in apoAII (-16.59 +/-66.15 MUg/mL, P = 0.0075) and apoE (-2.66 +/- 12.64 MUg/mL, P = 0.015) persisted at 4 weeks of post-treatment follow-up. In multivariate analysis, treatment with LDV/SOF + RBV was independently associated with reduction in apoE (beta = 5.31 MUg/mL, P = 0.002) (compared to RBV-free LDV/SOF) (P < 0.05). In contrast, apoCII levels overall increased from baseline to end of treatment (+2.74 +/-11.76 MUg/mL, P = 0.03) and persisted at 4 weeks of follow-up (+4.46 +/- 12.81 MUg/mL from baseline, P = 0.0005). Subgroup analysis revealed an increase in apoCII during treatment only in patients receiving LDV/SOF without RBV (+5.52 +/- 11.92 MUg/mL, P = 0.0007) but not in patients receiving LDV/SOF + RBV (P = 0.638). Treatment with LDV/SOF +/- RBV is associated with a persistent reduction in the apolipoprotein AII and E after achieving cure. These data suggest that treatment with LDV/SOF +/- RBV may be associated with alterations in serum apolipoproteins which could potentially impact viral eradication. PMID- 26280788 TI - Nutrition Support for Athletes. PMID- 26280789 TI - Dietitians' Perspectives on Interventions to Enhance Adherence to Dietary Advice for Chronic Diseases in Adults. AB - PURPOSE: To assess dietitians' perspectives on the importance and applicability of interventions to enhance adherence to dietary advice for preventing and managing chronic diseases in adults in the Canadian context. METHODS: Based on a Cochrane systematic review, we identified 8 promising interventions for enhancing adherence to dietary advice: behavioural contracts, exchange lists, feedback based on self-monitoring, individualized menu suggestions, multiple interventions, portion size awareness, telephone follow-up, and videos. Thirty two dietitians then completed a 3-round Delphi study by responding to an electronic questionnaire asking them to rate the importance and applicability in their practice of the 8 interventions on a 7-point Likert scale. RESULTS: Using a >=75% level of agreement, 4 interventions showed strong consensus: multiple interventions, feedback based on self-monitoring, portion size awareness, and videos. Among these, the most significant were (means +/- SD for importance and applicability, respectively) feedback based on self-monitoring (6.97 +/- 0.18 and 6.72 +/- 0.46), portion size awareness (6.69 +/- 0.54 and 6.75 +/- 0.51), and multiple interventions (6.94 +/- 0.25 and 6.81 +/- 0.40). CONCLUSIONS: These findings can guide the development of educational training sessions for dietitians to help them provide practice-relevant interventions that will increase the likelihood that patients adhere to their advice regarding prevention and management of chronic diseases. PMID- 26280790 TI - Bioavailability and Safety of Vitamin D3 from Pizza Baked with Fortified Mozzarella Cheese: A Randomized Controlled Trial. AB - PURPOSE: To assess the bioavailability and safety of vitamin D3 from fortified mozzarella cheese baked on pizza. METHODS: In a randomized, double-blind trial, 96 apparently healthy, ethnically diverse adults were randomized to consume 200 IU or 28 000 IU vitamin D3 fortified mozzarella cheese with pizza once weekly for a total of 8 weeks. Blood and urine samples were collected at baseline (week 1) and final (week 10) visits for serum 25-hydroxyvitamin D and other biochemical measures. The primary outcome compared serum 25-hydroxyvitamin D between groups at 10 weeks. The secondary outcome evaluated the safety of vitamin D dosing protocol as measured by serum and urine calcium, phosphate, creatinine, and serum parathyroid hormone (PTH). RESULTS: Serum 25-hydroxyvitamin D increased by 5.1 +/ 11 nmol/L in the low-dose group (n = 47; P = 0.003), and by 73 +/- 22 nmol/L in the high-dose group (n = 49; P < 0.0001). None of the subjects in either group developed any adverse events during the supplementation protocol. Serum PTH significantly decreased in the high-dose group only (P < 0.05). CONCLUSIONS: Vitamin D3 is safe and bioavailable from fortified mozzarella cheese baked on pizza. PMID- 26280791 TI - Socioeconomic and Cultural Correlates of Diet Quality in the Canadian Arctic: Results from the 2007-2008 Inuit Health Survey. AB - PURPOSE: We examined the impact of socioeconomic and cultural factors on dietary quality in adult Inuit living in the Canadian Arctic. METHODS: Interviews and a 24-h dietary recall were administered to 805 men and 1292 women from Inuit regions in the Canadian Arctic. We examined the effect of age, sex, education, income, employment, and cultural variables on respondents' energy, macronutrient intake, sodium/potassium ratio, and healthy eating index. Logistic regression was used to assess the impact of socioeconomic status (SES) on diet quality indicators. RESULTS: Age was positively associated with traditional food (TF) consumption and greater energy from protein but negatively associated with total energy and fibre intake. Associations between SES and diet quality differed considerably between men and women and there was considerable regional variability in diet quality measures. Age and cultural variables were significant predictors of diet quality in logistic regression. Increased age and use of the Inuit language in the home were the most significant predictors of TF consumption. CONCLUSIONS: Our findings are consistent with studies reporting a nutrition transition in circumpolar Inuit. We found considerable variability in diet quality and complex interaction between SES and cultural variables producing mixed effects that differ by age and gender. PMID- 26280792 TI - Impact Evaluation of an After-school Cooking Skills Program in a Disadvantaged Community: Back to Basics. AB - PURPOSE: Few efficacious child obesity interventions have been converted into ongoing community programs in the after-school setting. The aim of this study was to evaluate the impact of phase 2 of the Back to Basics cooking club on dietary behaviours and fruit and vegetable variety in a population at risk of obesity at a low income school with > 10% indigenous population. METHODS: Baseline and 3 month dietary intake and social cognitive theory (SCT) constructs were collected in 51 children, mean age 9 years, 61% female. McNemar tests were used for comparison of proportions between categorical variables. Cohen's d was used to compare effect sizes across different measures. RESULTS: Consumption of one or more fruit servings per day significantly increased from 41% to 67% (P = 0.02, d = 0.13) and there was a trend for increasing the weekly variety of fruit and vegetables. The SCT constructs assessed within the current study improved significantly (P < 0.05), with moderate to large effect sizes (d = 0.33-0.78). CONCLUSION: This study documents that a previous efficacious healthy lifestyle program can be adapted for use as an obesity prevention program addressing improvements in vegetable and fruit intakes in a low income community with a relatively high indigenous population. PMID- 26280793 TI - The Impact of School Gardening on Cree Children's Knowledge and Attitudes toward Vegetables and Fruit. AB - PURPOSE: School-based interventions may increase children's preferences for vegetables and fruit (V&F). This Canadian study measured changes in Indigenous First Nations schoolchildren's V&F knowledge, preferences, and home consumption following the implementation of a gardening and V&F snack program. METHODS: At baseline, 7 months, and 18 months, children in grades 1-6 (i) listed at least 5 V&F they knew, (ii) tasted and indicated their preferences towards 9 vegetables and 8 fruit using a 6-point Likert scale, and (iii) indicated their home consumption of 17 V&F. RESULTS: At all 3 time points, 56.8% (n = 66/116) of children provided data. Children listed a greater number of V&F at 18 months (4.9 +/- 0.1) than at baseline (4.5 +/- 1.0) or 7 months (4.7 +/- .07) (F(1.6,105.6) = 6.225, P < 0.05). Vegetable preferences became more positive between baseline (37.9 +/- 9.3) and 7 months (39.9 +/- 9.2), but returned to baseline levels at 18 months (37.3 +/- 8.7) (F(1.6,105.8) = 4.581, P < 0.05). Fruit preferences at 18 months (42.7 +/- 3.0) were greater than at baseline (41.1 +/- 4.3) and at 7 months (41.9 +/- 5.1) (F(1.7,113.3) = 3.409, P < 0.05). No change in V&F consumption occurred at home. CONCLUSIONS: Despite improvements in V&F knowledge and preferences, home consumption of V&F did not occur. Complementing school based programs with home-based components may be needed to influence V&F intake of children. PMID- 26280794 TI - Food Literacy: Definition and Framework for Action. AB - The term food literacy is emergent, and as a result the literature reflects a great variety of definitions. Simultaneously, new research and food literacy programming is being developed without an agreed upon definition of what food literacy is and how food skills, food security, and health literacy may fit with the definition. We undertook a scoping review and conceptual analysis to identify how the term is understood and to determine shared components of definitions. We found that although most definitions included a nutrition and food skills component, there was great variation in how the ability to access, process, and enjoy food was affected by our complex food system. We propose a definition of food literacy that includes the positive relationship built through social, cultural, and environmental experiences with food enabling people to make decisions that support health. We offer a framework that situates food literacy at the intersection between community food security and food skills, and we assert that behaviours and skills cannot be separated from their environmental or social context. The proposed definition and framework are intended to be guiding templates for academics and practitioners to position their work in education and advocacy, bringing together separate spheres for collective action. PMID- 26280795 TI - Awareness and Knowledge of Recommendations from Canada's Food Guide. AB - PURPOSE: To examine use and content knowledge of Canada's Food Guide recommendations. METHODS: A total of 1048 intercept exit surveys were conducted with adults who had purchased food that day at 2 hospital cafeterias in Ottawa, Ontario. RESULTS: Most respondents (85.9%) reported looking at Canada's Food Guide over their lifetime; however, less than half reported looking at the food guide in the past year. Milk and Alternatives were the most commonly recalled food group (80.1%) and Grain Products were least commonly recalled (66.0%). Of the entire sample, 42.8% correctly recalled all 4 food groups. Overall, 0.8% correctly recalled the correct number of servings for all 4 food groups. Females, younger respondents, white respondents, respondents with higher annual income, and respondents who had reported looking at Canada's Food Guide recalled more food groups (P < 0.05 for all). CONCLUSIONS: Despite high levels of awareness, the study found relatively low levels of reported use and very low levels of knowledge of Canada's Food Guide, particularly among population subgroups that face health disparities. Improving awareness, knowledge, and use of Canada's Food Guide may contribute to improving the nutrition profile of Canadians. PMID- 26280796 TI - A Lifetime Pursuit of a Sports Nutrition Practice. AB - Sports nutrition in Canada has significantly evolved over the years from providing fundamental training dietary advice to applied precise assessment of nutritional status in a variety of settings, especially with the establishment of Canadian Sport Institutes and Centres across Canada. This progression has enhanced the level of dietary support to manage athletes' nutrition in a holistic perspective. Athletes are now educated about food fundamentals (acquiring foods, menu planning, preparing, food safety), personal accountability of hydration and energy monitoring (urinary and body weight assessments), individualized supplementation protocols, and customized nutrition for variable daily training environments according to their Yearly Training Plan. Sport dietitians are an important member of Integrated Sport Teams where collaboration exists amongst professionals who coordinate the athletes' personalized training and performance programming. Dietitians in sport are encouraged to continue to lobby for nutrition programming at the elite, varsity, provincial, and club levels to ensure that athletes receive accurate guidance from nutrition experts. PMID- 26280798 TI - Pregnancy Rates to Fixed Embryo Transfer of Vitrified IVP Bos indicus, Bos taurus or Bos indicus * Bos taurus Embryos. AB - The pregnancy rates obtained after the transfer of cryopreserved in vitro produced (IVP) embryos are usually low and/or inconsistent. The objective of this study was to evaluate the pregnancy rates of Holstein, Gyr and Holstein * Gyr cattle after the transfer of vitrified IVP embryos produced with X-sorted sperm. Seventy-two Gyr and 703 Holstein females were subjected to ovum pickup (OPU) sessions, followed by in vitro embryo production using semen from sires of the same breeds. Embryos (1636 Holstein, 241 Gyr and 1515 Holstein * Gyr) were exposed to forskolin for 48 h prior to vitrification. The pregnancy rate achieved with Gyr dam and sire was 46.1%, which was similar (p = 0.11) to that of Holstein dam and Gyr sire (40.3%). Crossing Gyr dams with Holstein sires resulted in a pregnancy rate of 38.9% and did not differ (p = 0.58) from the pregnancy rate obtained with the cross between Holstein dams and Gyr sires. The rate obtained with Holstein dam and sire was 32.5%. The average pregnancy rate was 36.6%, and no difference was found in the proportion of female foetuses (88.8%, in average) among breeds (p > 0.05). In conclusion, transfer of cryopreserved X-sorted embryos represents an interesting choice for dairy cattle. Despite the small differences between pregnancy rates, we highlight the efficiency of this strategy for all of the racial groups studied. PMID- 26280799 TI - Aggregation and Stability of Reduced Graphene Oxide: Complex Roles of Divalent Cations, pH, and Natural Organic Matter. AB - The aggregation and stability of graphene oxide (GO) and three successively reduced GO (rGO) nanomaterials were investigated. Reduced GO species were partially reduced GO (rGO-1h), intermediately reduced GO (rGO-2h), and fully reduced GO (rGO-5h). Specifically, influence of pH, ionic strength, ion valence, and presence of natural organic matter (NOM) were studied. Results show that stability of GO in water decreases with successive reduction of functional groups, with pH having the greatest influence on rGO stability. Stability is also dependent on ion valence and the concentration of surface functional groups. While pH did not noticeably affect stability of GO in the presence of 10 mM NaCl, adding 0.1 mM CaCl2 reduced stability of GO with increased pH. This is due to adsorption of Ca(2+) ions on the surface functional groups of GO which reduces the surface charge of GO. As the concentration of rGO functional groups decreased, so did the influence of Ca(2+) ions on rGO stability. Critical coagulation concentrations (CCC) of GO, rGO-1h, and rGO-2h were determined to be ~ 200 mM, 35 mM, and 30 mM NaCl, respectively. In the presence of CaCl2, CCC values of GO and rGO are quite similar, however. Long-term studies show that a significant amount of rGO-1h and rGO-2h remain stable in Call's Creek surface water, while effluent wastewater readily destabilizes rGO. In the presence NOM and divalent cations (Ca(2+), Mg(2+)), GO aggregates settle from suspension due to GO functional group bridging with NOM and divalent ions. However, rGO-1h and rGO-2h remain suspended due to their lower functional group concentration and resultant reduced NOM-divalent cation bridging. Overall, pH, divalent cations, and NOM can play complex roles in the fate of rGO and GO. PMID- 26280800 TI - Fermentanomics: Relating quality attributes of a monoclonal antibody to cell culture process variables and raw materials using multivariate data analysis. AB - Fermentanomics is an emerging field of research and involves understanding the underlying controlled process variables and their effect on process yield and product quality. Although major advancements have occurred in process analytics over the past two decades, accurate real-time measurement of significant quality attributes for a biotech product during production culture is still not feasible. Researchers have used an amalgam of process models and analytical measurements for monitoring and process control during production. This article focuses on using multivariate data analysis as a tool for monitoring the internal bioreactor dynamics, the metabolic state of the cell, and interactions among them during culture. Quality attributes of the monoclonal antibody product that were monitored include glycosylation profile of the final product along with process attributes, such as viable cell density and level of antibody expression. These were related to process variables, raw materials components of the chemically defined hybridoma media, concentration of metabolites formed during the course of the culture, aeration-related parameters, and supplemented raw materials such as glucose, methionine, threonine, tryptophan, and tyrosine. This article demonstrates the utility of multivariate data analysis for correlating the product quality attributes (especially glycosylation) to process variables and raw materials (especially amino acid supplements in cell culture media). The proposed approach can be applied for process optimization to increase product expression, improve consistency of product quality, and target the desired quality attribute profile. PMID- 26280801 TI - Thermodynamic and Probabilistic Metabolic Control Analysis of Riboflavin (Vitamin B2) Biosynthesis in Bacteria. AB - In this study, we applied a coupled in silico thermodynamic and probabilistic metabolic control analysis methodology to investigate the control mechanisms of the commercially relevant riboflavin biosynthetic pathway in bacteria. Under the investigated steady-state conditions, we found that several enzyme reactions of the pathway operate far from thermodynamic equilibrium (transformed Gibbs energies of reaction below about -17 kJ mol(-1)). Using the obtained thermodynamic information and applying enzyme elasticity sampling, we calculated the distributions of the scaled concentration control coefficients (CCCs) and scaled flux control coefficients (FCCs). From the statistical analysis of the calculated distributions, we inferred that the control over the riboflavin producing flux is shared among several enzyme activities and mostly resides in the initial reactions of the pathway. More precisely, the guanosine triphosphate (GTP) cyclohydrolase II activity, and therefore the bifunctional RibA protein of Bacillus subtilis because it catalyzes this activity, appears to mainly control the riboflavin producing flux (mean FCCs = 0.45 and 0.55, respectively). The GTP cyclohydrolase II activity and RibA also exert a high positive control over the riboflavin concentration (mean CCCs = 2.43 and 2.91, respectively). This prediction is consistent with previous findings for microbial riboflavin overproducing strains. PMID- 26280802 TI - Screening of Phosphorus-Accumulating Fungi and Their Potential for Phosphorus Removal from Waste Streams. AB - While bacteria have been primarily studied for phosphorus (P) removal in wastewater treatment, fungi and their ability to accumulate intracellular polyphosphate are less investigated. P-accumulating fungal strains were screened from soybean plants and surrounding soil by flask cultivation with potato dextrose broth and KH2PO4 in this study. Mucor circinelloides was selected for its high efficiency in P removal efficiency and high cellular P content. Neisser staining and growth-curve analysis confirmed that M. circinelloides stored polyphosphate intracellularly by luxury phosphate uptake. The effect of culture medium compositions on P removal efficiency and cellular P content was also investigated. Monosaccharides (such as glucose and fructose) and organic nitrogen (N, such as urea, and peptone) promoted fungi growth and P accumulation. M. circinelloides also preferred organic phosphates. When glucose, urea, and phytic acid sodium salt were used as the carbon, N, and P source, respectively, the maximum utilization efficiency was 40.1% for P and 7.08% for cellular P content. In addition, the potential of M. circinelloides for P removal from waste streams was investigated. Compared with the non-inoculated control culture, inoculation with M. circinelloides improved the soluble P removal in treating wastewater centrate, screened manure, and digested manure. PMID- 26280803 TI - Strategy to Overcome Effect of Raw Materials on Enzymatic Process of Biodiesel from Non-edible Oils Using Candida sp. 99-125 Lipase. AB - Non-edible oils are preferred raw materials for biodiesel production. However, the properties of raw materials significantly affect the synthesis process, leading to difficulties to design one process suitable for any kind of raw material. In this study, the composition of five typical non-edible oils was analyzed. The major difference was the content of free fatty acids, reflected from their acid values. The influence of different oils was investigated by using lipase from Candida sp. 99-125. At low lipase dosage and low water content, the conversion was found proportional to the acid value. However, by increasing the water content or lipase dosage, we observed that the conversions for all kinds of oils used in this study could exceed 80%. Time course analysis indicates that the lipase used in this study catalyzed hydrolysis followed by esterification, rather than direct transesterification. Accumulation of free fatty acids at the very beginning was necessary. A high water content facilitated the hydrolysis of oils with low acid value. This lipase showed capability to transform all the oils by controlling the water content. PMID- 26280804 TI - Texting while driving as impulsive choice: A behavioral economic analysis. AB - The goal of the present study was to examine the utility of a behavioral economic analysis to investigate the role of delay discounting in texting while driving. A sample of 147 college students completed a survey to assess how frequently they send and read text messages while driving. Based on this information, students were assigned to one of two groups: 19 students who frequently text while driving and 19 matched-control students who infrequently text while driving but were similar in gender, age, years of education, and years driving. The groups were compared on the extent to which they discounted, or devalued, delayed hypothetical monetary rewards using a delay-discounting task. In this task, students made repeated choices between $1000 available after a delay (ranging from 1 week to 10 years) and an equal or lesser amount of money available immediately. The results show that the students who frequently text while driving discounted delayed rewards at a greater rate than the matched control students. The study supports the conclusions that texting while driving is fundamentally an impulsive choice made by drivers, and that a behavioral economic approach may be a useful research tool for investigating the decision-making processes underlying risky behaviors. PMID- 26280805 TI - Intravenous anesthesia in treatment of nonconvulsive status epilepticus: Characteristics and outcomes. AB - OBJECTIVE: To determine factors associated with continuous anesthetic drug (IVAD) use in nonconvulsive status epilepticus (NCSE). METHODS: Retrospective cohort study of patients who met clinical and EEG criteria of NCSE from 2009 to 2014 at a tertiary academic medical center. Patients were categorized according to IVAD use. Outcome variables were response to treatment and in-hospital death. We used descriptive analyses for baseline characteristics and outcome variable differences among patients who did and did not receive IVAD. RESULTS: Forty-three patients had a total of 45 NCSE episodes. IVAD was used in 69% of the episodes. Patients treated with IVAD were younger (53.1 +/- 14.1 vs 64.1 +/- 13.3, p = 0.019). The episodes treated with IVAD occurred more frequently in patients with an acute neurologic pathology (58% vs 21%, p = 0.024) and those presenting in a coma (39% vs 7%, p = 0.030). NCSE resolved in 74% of the patients who received IVAD. Duration of NCSE did not differ significantly by treatment group. There were total 13 in-hospital deaths: ten in IVAD users vs three in the no-IVAD group (p > 0.05). Only one in-hospital death appeared to be a direct consequence of IVAD use. Mortality was more common among episodes that were not treated according to the published status epilepticus treatment guidelines compared to the episodes where guidelines were followed. CONCLUSION: Our findings showed that factors such as younger age, acute neurologic pathology and coma at presentation were associated with IVAD use in patients with NCSE. These factors should be controlled in the future outcome and effectiveness studies to determine the effect of IVAD use on outcome of NCSE. PMID- 26280806 TI - Improving the inter-rater agreement of hypsarrhythmia using a simplified EEG grading scale for children with infantile spasms. AB - BACKGROUND: There is poor inter-rater agreement in determining the presence or absence of hypsarrhythmia among patients with infantile spasms. Yet, remission of hypsarrhythmia has been used as a clinical and research outcome measure. Two important features of hypsarrhythmia are the burden of epileptiform discharges and the amplitudes of background slow waves. We hypothesized that an electroencephalogram (EEG) grading scale emphasizing epileptiform discharge burden and the amplitudes of background slow waves would improve inter-rater agreement in interpreting hypsarrhythmia. Our aim was to assess inter-rater agreement of hypsarrhythmia using a novel and simplified EEG grading scale called the 'BASED' (Burden of Amplitudes and Epileptiform Discharges) score and compare this to the traditional method of EEG analysis. METHODS: Twenty patients with infantile spasms were prospectively evaluated and electroclinical outcomes were determined. Forty EEG clips (20 pre-treatment and 20 post-treatment), representing the most severely abnormal five minute sleep epoch of each study, were assessed by three reviewers blinded to treatment and clinical outcome. Fleiss' kappa (K) was used to assess the inter-rater agreement in the interpretation of hypsarrhythmia when using the BASED score compared to the traditional method of EEG analysis. RESULTS: Reviewers had favorable inter-rater agreement using the BASED score in interpreting hypsarrhythmia (K: 0.87) compared to when using the traditional method of EEG analysis to interpret hypsarrhythmia (K: 0.09). The three reviewers all agreed on the presence or absence of hypsarrhythmia in 37/40 (93%) epochs using the BASED score but in only 15/40 (38%) epochs using the traditional method of EEG analysis, p=<0.001. CONCLUSION: When compared to the traditional method of EEG analysis, the BASED score allowed for better inter-rater agreement in the interpretation of hypsarrhythmia. Future infantile spasms clinical trials must better define criteria for hypsarrhythmia. PMID- 26280808 TI - Overweight and obesity decreased in Greek schoolchildren from 2009 to 2012 during the early phase of the economic crisis. AB - AIM: We examined the weight status of Greek schoolchildren from November 2009 to May 2012, shortly before, and during the early years, of the Greek economic crisis. METHODS: This was a mixed longitudinal study that formed part of the West Attica Growth Study and followed children at the ages of 6-7, 9-10, 12-13 and 15 16 years every six months for 2.5 years. Each child's height and weight were measured and their body mass index calculated. We were able to determine the weight status of 1327 children (53% boys) based on their first and last measurements. Overweight, obesity and underweight were defined using the International Obesity Task Force criteria. RESULTS: During the 2.5-year study period, there was a decrease in the total prevalence of overweight and obesity, which reached a statistical significance for both sexes. It decreased from 43% to 37.3% (p = 0.02) in boys and from 33.4% to 26.9% (p = 0.0056) in girls. There was also a statistically significant increase in normal weight children and a slight but insignificant increase in underweight children of both sexes. CONCLUSION: During the initial years of the Greek economic crisis, there was a statistically significant reduction in overweight and obesity in children from six to 16 years of age. PMID- 26280807 TI - G Protein-Coupled Receptor 120 Signaling Negatively Regulates Osteoclast Differentiation, Survival, and Function. AB - G protein-coupled receptor 120 (GPR120) plays an important role in the regulation of inflammation and lipid metabolism. In this study, we investigated the role of GPR120 in osteoclast development and found that GPR120 regulates osteoclast differentiation, survival and function. We observed that GPR120 was highly expressed in osteoclasts compared to their precursors, bone marrow-derived macrophages (BMMs). Activation of GPR120 by its ligand GW9508 suppressed receptor activator of NF- kappaB ligand (RANKL)-induced osteoclast differentiation and the expression of nuclear factor of activated T cells c1 (NFATc1), a key modulator of osteoclastogenesis. GPR120 activation further inhibited the RANKL-stimulated phosphorylation of IkappaBalpha and JNK. In addition to osteoclast differentiation, GPR120 activation increased the apoptosis of mature osteoclasts by inducing caspase-3 and Bim expression. Activation of GPR120 also interfered with cell spreading and actin cytoskeletal organization mediated by M-CSF but not by RANKL. Coincident with the impaired cytoskeletal organization, GPR120 activation blocked osteoclast bone resorbing activity. Furthermore, knockdown of GPR120 using small hairpin RNA abrogated all these inhibitory effects on osteoclast differentiation, survival, and function. Together, our findings identify GPR120 as a negative modulator of osteoclast development that may be an attractive therapeutic target for bone-destructive diseases. J. Cell. Physiol. 231: 844-851, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26280809 TI - Sorption of Water and Initial Stages of Swelling of Thin PNIPAM Films Using in Situ GISAXS Microfluidics. AB - The sorption of low-molecular penetrants by thin polymer films, as well as structural changes provoked therein, is of high relevance for many fields of application. Complex permeation, diffusion, swelling, and dissolution processes are often induced within films by solvents or gases. Here, we use a novel in situ microfluidics-grazing incidence small-angle X-ray scattering (GISAXS) setup to examine changes in film thickness and in the surface structure of a thin polymer film that sorbs a good solvent. Thus, this technique is highly complementary to the established techniques on the field of diffusion in polymers. The initial stages of water uptake and swelling are resolved for a 50 nm thin, hydrophilic poly(N-isopropylacrylamide) (PNIPAM) film, before its dissolution sets in. The initial stages of swelling are tentatively described by anomalous swelling induced by a time- and space-dependent diffusion coefficient. PMID- 26280810 TI - Enhanced Power-Conversion Efficiency in Inverted Bulk Heterojunction Solar Cells using Liquid-Crystal-Conjugated Polyelectrolyte Interlayer. AB - Two novel liquid-crystal-conjugated polyelectrolytes (LCCPEs) poly[9,9-bis[6-(4 cyanobiphenyloxy)-hexyl]-fluorene-alt-9,9-bis(6-(N,N-diethylamino)-hexyl) fluorene] (PF6Ncbp) and poly[9,9-bis[6-(4-cyanobiphenyloxy)-hexyl]-fluorene-alt 9,9-bis(6-(N-methylimidazole)-hexyl]-fluorene] (PF6lmicbp) are obtained by covalent linkage of the cyanobiphenyl mesogen polar groups onto conjugated polyelectrolytes. After deposition a layer of LCCPEs on ZnO interlayer, the spontaneous orientation of liquid-crystal groups can induce a rearrangement of dipole moments at the interface, subsequently leading to the better energy-level alignment. Moreover, LCCPEs favors intimate interfacial contact between ZnO and the photon harvesting layer and induce active layer to form the nanofibers morphology for the enhancement of charge extraction, transportation and collection. The water/alcohol solubility of the LCCPEs also enables them to be environment-accepted solvent processability. On the basis of these advantages, the poly(3-hexylthiophene) (P3HT):[6,6]-phenyl-C60-butyric acid methyl ester (PC60BM)-based inverted polymer solar cells (PSCs) combined with ZnO/PF6Ncbp and ZnO/PF6lmicbp bilayers boost the power conversion efficiency (PCE) to 3.9% and 4.2%, respectively. Incorporation of the ZnO/PF6lmicbp into the devices based on a blend of a narrow band gap polymer thieno[3,4-b]thiophene/benzodithiophene (PTB7) with [6,6]-phenyl C70-butyric acid methyl ester (PC71BM) affords a notable efficiency of 7.6%. PMID- 26280811 TI - Screening for Elder Abuse and Neglect. PMID- 26280812 TI - The Tsimane' Amazonian Panel Study (TAPS): Nine years (2002-2010) of annual data available to the public. AB - This brief communication contains a description of the 2002-2010 annual panel collected by the Tsimane' Amazonian Panel Study team. The study took place among the Tsimane', a native Amazonian society of forager-horticulturalists. The team tracked a wide range of socio-economic and anthropometric variables from all residents (633 adults >=16 years; 820 children) in 13 villages along the Maniqui River, Department of Beni. The panel is ideally suited to examine how market exposure and modernization affect the well-being of a highly autarkic population and to examine human growth in a non-Western rural setting. PMID- 26280813 TI - Functionalized Agarose Self-Healing Ionogels Suitable for Supercapacitors. AB - Agarose has been functionalized (acetylated/carbanilated) in an ionic liquid (IL) medium of 1-butyl-3-methylimidazolium acetate at ambient conditions. The acetylated agarose showed a highly hydrophobic nature, whereas the carbanilated agarose could be dissolved in water as well as in the IL medium. Thermoreversible ionogels were obtained by cooling the IL sols of carbanilated agarose at room temperature. The ionogel prepared from a protic-aprotic mixed-IL system (1-butyl 3-methylimidazolium chloride and N-(2-hydroxyethyl)ammonium formate) demonstrated a superior self-healing property, as confirmed from rheological measurements. The superior self-healing property of such an ionogel has been attributed to the unique inter-intra hydrogen-bonding network of functional groups inserted in the agarose. The ionogel was tested as a flexible solid electrolyte for an activated carbon-based supercapacitor cell. The measured specific capacitance was found to be comparable with that of a liquid electrolyte system at room temperature and was maintained for up to 1000 charge-discharge cycles. Such novel functionalized biopolymer self-healing ionogels with flexibility and good conductivity are desirable for energy-storage devices and electronic skins with superior lifespans and robustness. PMID- 26280814 TI - Laser ablation therapy: An alternative treatment for medically resistant mesial temporal lobe epilepsy after age 50. AB - Selective anterior mesial temporal lobe (AMTL) resection is considered a safe and effective treatment for medically refractory mesial temporal lobe epilepsy (MTLE). However, as with any open surgical procedure, older patients (aged 50+) face greater risks. Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has shown recent potential as an alternative treatment for MTLE. As a less invasive procedure, MRgLITT could be particularly beneficial to older patients. To our knowledge, no study has evaluated the safety and efficacy of MRgLITT in this population. Seven consecutive patients (aged 50+) undergoing MRgLITT for MTLE were followed prospectively to assess surgical time, complications, postoperative pain control, length of stay (LOS), operating room (OR) charges, total hospitalization charges, and seizure outcome. Five of these patients were assessed at the 1-year follow-up for seizure outcome. These data were compared with data taken from 7 consecutive patients (aged 50+) undergoing AMTL resection. Both groups were of comparable age (mean: 60.7 (MRgLITT) vs. 53 (AMTL)). One AMTL resection patient had a complication of aseptic meningitis. One MRgLITT patient experienced an early postoperative seizure, and two MRgLITT patients had a partial visual field deficit. Seizure-freedom rates were comparable (80% (MRgLITT) and 100% (AMTL) (p>0.05)) beyond 1year postsurgery (mean follow-up: 1.0years (MRgLITT) vs. 1.8years (AMTL)). Mean LOS was shorter in the MRgLITT group (1.3days vs. 2.6days (p<0.05)). Neuropsychological outcomes were comparable. Short-term follow-up suggests that MRgLITT is safe and provides outcomes comparable to AMTL resection in this population. It also decreases pain medication requirement and reduces LOS. Further studies are necessary to assess the long-term efficacy of the procedure. PMID- 26280816 TI - Fractional laser-assisted drug delivery: Active filling of laser channels with pressure and vacuum alteration. AB - BACKGROUND AND OBJECTIVE: Ablative fractional laser (AFXL) is rapidly evolving as one of the foremost techniques for cutaneous drug delivery. While AFXL has effectively improved topical drug-induced clearance rates of actinic keratosis, treatment of basal cell carcinomas (BCCs) has been challenging, potentially due to insufficient drug uptake in deeper skin layers. This study sought to investigate a standardized method to actively fill laser-generated channels by altering pressure, vacuum, and pressure (PVP), enquiring its effect on (i) relative filling of individual laser channels; (ii) cutaneous deposition and delivery kinetics; (iii) biodistribution and diffusion pattern, estimated by mathematical simulation. METHODS: Franz diffusion chambers (FCs) were used to evaluate the PVP-technique, comparing passive (AFXL) and active (AFXL + PVP) channel filling. A fractional CO2-laser generated superficial (225 um;17.5 mJ/channel) and deep (1200 um; 130.5 mJ/channel) channels, and PVP was delivered as a 3-minutes cycle of 1 minute pressure (+1.0 atm), 1 minute vacuum (-1.0 atm), and 1 minute pressure (+1.0 atm). Filling of laser channels was visualized with a colored biomarker liquid (n = 12 FCs, n = 588 channels). Nuclear magnetic resonance quantified intracutaneous deposition of topically applied polyethylene glycol (PEG400) over time (10 minutes, 1 hour, and 4 hours), investigated with (n = 36 FCs) and without (n = 30 FCs) PVP-filling. Two-dimensional mathematical simulation was used to simulate intradermal biodistribution and diffusion at a depth of 1,000 um. RESULTS: Active filling with application of PVP increased the number of filled laser channels. At a depth of 1,000 um, filling increased from 44% (AFXL) to 94% with one PVP cycle (AFXL + PVP; P < 0.01). Active filling greatly enhanced intracutaneous deposition of PEG400, resulting in a rapid delivery six-folding uptake at 10 minutes (AFXL 54 ug/ml vs. AFXL + PVP 303 ug/ml, P < 0.01). AFXL alone generated an inhomogeneous uptake of PEG400, which greatly improved with active filling, resulting in a uniform uptake within the entire tissue. CONCLUSION: Active filling with PVP secures filling of laser channels and induces a deeper, greater, more rapid delivery than conventional AFXL. This delivery technique has promise to improve treatment efficacy for medical treatments of dermally invasive lesions, such as BCCs. PMID- 26280815 TI - Assessment of long-term outcomes associated with urinary prostate cancer antigen 3 and TMPRSS2:ERG gene fusion at repeat biopsy. AB - BACKGROUND: In men with clinically localized prostate cancer who have undergone at least 1 previous negative biopsy and have elevated serum prostate-specific antigen (PSA) levels, long-term health outcomes associated with the assessment of urinary prostate cancer antigen 3 (PCA3) and the transmembrane protease, serine 2 (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) gene fusion (T2:ERG) have not been investigated previously in relation to the decision to recommend a repeat biopsy. METHODS: The authors performed a decision analysis using a decision tree for men with elevated PSA levels. The probability of cancer was estimated using the Prostate Cancer Prevention Trial Risk Calculator (version 2.0). The use of PSA alone was compared with the use of PCA3 and T2:ERG scores, with each evaluated independently, in combination with PSA to trigger a repeat biopsy. When PCA3 and T2:ERG score evaluations were used, predefined thresholds were established to determine whether the patient should undergo a repeat biopsy. Biopsy outcomes were defined as either positive (with a Gleason score of <7, 7, or >7) or negative. Probabilities and estimates of 10-year overall survival and 15-year cancer-specific survival were derived from previous studies and a literature review. Outcomes were defined as age-dependent and Gleason score dependent 10-year overall and 15-year cancer-specific survival rates and the percentage of biopsies avoided. RESULTS: Incorporating the PCA3 score (biopsy threshold, 25; generated based on the urine PCA3 level normalized to the amount of PSA messenger RNA) or the T2:ERG score (biopsy threshold, 10; based on the urine T2:ERG level normalized to the amount of PSA messenger RNA) into the decision to recommend repeat biopsy would have avoided 55.4% or 64.7% of repeat biopsies for the base-case patient, respectively, and changes in the 10-year survival rate were only 0.93% or 1.41%, respectively. Multi-way sensitivity analyses suggested that these results were robust with respect to the model parameters. CONCLUSIONS: The use of PCA3 or T2:ERG testing for repeat biopsy decisions can substantially reduce the number of biopsies without significantly affecting 10-year survival. PMID- 26280817 TI - Isolation and structural characterization of Coryxin, a novel cyclic lipopeptide from Corynebacterium xerosis NS5 having emulsifying and anti-biofilm activity. AB - Herein we reported the structure and several properties of a new biosurfactants produced by Corynebacterium xerosis strain NS5. This strain was capable of producing a novel lipopeptide biosurfactant that we have named coryxin. The biosurfactant structure was characterized by using Fourier transform infrared spectroscopy (FTIR), Nuclear magnetic resonance spectroscopy (NMR), and Liquid chromatography-mass spectrometry (LC-MS). It contained a hydrophobic moiety of 3 hydroxydecanoic acid and a peptide part predicted as a sequence of seven amino acids including Asn-Arg-Asn-Gln-Pro-Asn-Ser. Coryxin lowered the surface tension of water to 31.4 mN/m, with a critical micelle concentration of 25mg/l. It was a strong emulsifier with an emulsification index of 61% against n-hexane. Coryxin showed antibacterial activity against test organisms belonging to Gram-positive and Gram-negative bacteria and disrupted preformed biofilms of Staphylococcus aureus (82.5%), Streptococcus mutans (80%), Escherichia coli (66%) and Pseudomonas aeruginosa (30%). In conclusion, microbial surfactant from C. xerosis exhibited inhibitory and disruptive activities against biofilm formation that could be of use in biofilm-related menace. PMID- 26280818 TI - Lipid nanocapsules as a new delivery system in copepods: Toxicity studies and optical imaging. AB - In this paper, we investigated the potential of lipid nanocapsules (LNCs) as a delivery system of small hydrophobic molecules, polycyclic aromatic hydrocarbons (PAHs) - pyrene, fluoranthene, phenanthrene, in the copepod Acartia tonsa. The LNCs were produced by a phase inversion process with a nominal size of 50 nm. These nanocapsules were obtained without organic solvent and with pharmaceutically acceptable excipients. The PAHs-LNCs displayed a stable monodisperse size distribution and a good stability in sea water for 7 days. By using fluorescent LNCs, it was possible to evidence LNCs ingestion by the copepods using confocal laser scanning microscopy. While blank LNCs are not toxic to copepods at tested concentrations, PAH-loaded LNCs were found to be very toxic on A. tonsa with a high mortality rate reaching 95% after 72 h exposure to 200 nM pyrene-loaded LNCs. On the other hand, when acetone is used to dissolve an equivalent concentration of PAHs in sea water, the copepod mortality is 10 times lower than using LNCs as nano-delivery system. This confirms the efficiency of using LNCs to deliver molecules directly in the gut or copepod carapace. The small size and non toxicity of these delivery nano-systems make them suitable for drug delivery to copepods. PMID- 26280819 TI - Chromenone-conjugated magnetic iron oxide nanoparticles. Toward conveyable DNA binders. AB - Magnetic nanoparticles can transport drug and possibly target cancer. DNA-binding of ligands loaded in dextran coated magnetic nanoparticles, could aid their better target-specific binding. In this work, we report the loading of chromenones onto aminoethylamino-modified dextran coated iron oxide nanoparticles, their loading efficiency, and openness for binding to DNA. The magnetic behavior, the size, and the morphology of the nanoparticles are analyzed. The crystallite size of the magnetic nanoparticles is around 40 nm. The chromenones are present on the surface of the dextran shell, as revealed by their cyclodextrin-binding characteristics, which is a new approach in comprehending the accessibility of the surface-bound molecules by macromolecules. The mode of binding of the chromenones to DNA is not altered on surface loading on dextran shell, although the binding strength is generally diminished, compared to the strength of binding of the free chromenones to DNA. PMID- 26280820 TI - Combination of elastic liposomes and low frequency ultrasound for skin permeation enhancement of hyaluronic acid. AB - HYPOTHESIS: The synergistic approach of using elastic liposomes (ELs) and low frequency ultrasound (LFU) was developed to enhance transepidermal delivery of hydrophilic macromolecules, hyaluronic acid (HA). EXPERIMENT: HA loaded ELs were prepared with varying cholesterol contents by reverse phase evaporation technique. Their mean sizes were evaluated using dynamic light scattering. Entrapment efficacy (%EE) was determined by UV-vis spectrophotometry. In vitro permeation studies using porcine ear epidermis were investigated. In addition, skin barrier disruption was assessed by transepidermal water loss and histology. FINDINGS: The HA loaded ELs showed mostly elliptical shaped with a mean size of ~ 700 nm and a zeta potential of ~-40 mV. Up to 77% drug entrapment efficiency was achieved. As ELs cholesterol content decreased, vesicle size, elasticity of liposomes and HA permeation profile increased. The in vitro permeation studies demonstrated that HA solution cannot permeate through the porcine epidermis. The combination of ELs/LFU showed greater HA permeation than ELs and HA/LFU, 2.1 times and 6.4 times, respectively. Increased LFU exposure times augmented HA permeation, but greater skin disruption was observed. Nevertheless, no skin damage was observed at the optimized 1 min exposure time. This ELs/LFU combination provides an efficacious protocol for transcutaneous drug delivery. PMID- 26280821 TI - Systemic complications of traumatic brain injury. AB - PURPOSE OF REVIEW: Increased understanding of the pathophysiology in traumatic brain injury (TBI) has resulted in the development of core physiological targets and therapies to preserve cerebral oxygenation, and in doing so prevent secondary insult. This review addresses the many systemic complications of TBI that make achieving these targets challenging and can influence outcome. RECENT FINDINGS: There are a wide range of systemic complications following TBI. Complications involve the cardiovascular, respiratory, immunological, haematological and endocrinological systems amongst others, and can influence early management and long-term outcomes. SUMMARY: Effective management of TBI should go beyond formulaic-based pursuit of physiological targets and requires a detailed understanding of the multisystem response of the body. PMID- 26280822 TI - Pain after surgery in children: clinical recommendations. AB - PURPOSE OF REVIEW: This article summarizes recent data related to the safety and efficacy of postoperative analgesia in children that influence clinical practice recommendations. RECENT FINDINGS: Postoperative pain continues to be experienced by hospitalized children and following discharge after short stay or ambulatory surgery. Updated recommendations for post-tonsillectomy analgesia exclude codeine and suggest regular administration of paracetamol and NSAID, but evidence for the most appropriate dose and type of opioid for rescue analgesia is limited. The incidence of opioid-related respiratory depression/oversedation in hospitalized children ranges from 0.11 to 0.41%, with recent large series identifying high risk groups and contributory factors that can be targeted to minimize the risk of serious or permanent harm. Data demonstrating feasibility and safety of regional analgesic techniques is increasing, but additional and procedure-specific evidence would improve technique selection and inform discussions of efficacy and safety with patients and families/carers. Persistent postsurgical pain is increasingly recognized following major surgery in adolescents. Evaluation of potential predictive factors in clinical studies and investigation of underlying mechanisms in laboratory studies can identify targets for both pharmacological and nonpharmacological interventions. SUMMARY: Recommendations for postoperative pain in children continue to evolve, with data incorporated from randomized controlled trials, case series and large audits. Management of pain following surgery in children needs to not only encompass efficacy and safety in the immediate perioperative period, but also consider pain following discharge after ambulatory surgery and the potential risk of persistent postsurgical pain following major surgery. PMID- 26280823 TI - Effect of Extra Virgin Olive Oil on Biomarkers of Inflammation in HIV-Infected Patients: A Randomized, Crossover, Controlled Clinical Trial. AB - BACKGROUND: Premature atherosclerosis in HIV-infected patients is associated with chronic infection by itself and adverse effects of antiretroviral treatment (ART). Extra virgin olive oil (EVOO) has a beneficial effect on the cardiovascular system because of its anti-inflammatory properties. The objective of this study was to determine whether the consumption of EVOO improves inflammation and atherosclerosis biomarkers in HIV-infected patients receiving ART. MATERIAL AND METHODS: This randomized, crossover, controlled trial included 39 HIV-positive male participants who consumed 50 mL of EVOO or refined olive oil (ROO) daily. Four participants dropped out of the study. Leukocyte count, erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hsCRP), interleukin-6, fibrinogen, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, malondialdehyde, glutathione-peroxidase, superoxide dismutase, oxidized LDL and von Willebrand factor were determined before the first and after each of the 2 intervention periods. Intervention and washout periods lasted for 20 and 14 days, respectively. RESULTS: In participants with >90% compliance (N=30), hsCRP concentrations were lower after EVOO intervention (geometric mean [GM], 1.70 mg/L; 95% confidence interval [CI], 1.15-2.52) compared to ROO administration (GM, 2.92 mg/L; 95% CI, 1.95-4.37) (p=0.035). In participants using lopinavir/ritonavir, ESR and hsCRP concentrations decreased 62% and 151%, respectively, after EVOO administration. In the whole study population (N=35) we found no difference in analyzed biomarkers after EVOO administration. CONCLUSIONS: Our exploratory study suggests that EVOO consumption could lower hsCRP in patients on ART. PMID- 26280824 TI - Proposal of Venous Drainage-Based Classification System for Carotid Cavernous Fistulae With Validity Assessment in a Multicenter Cohort. AB - BACKGROUND: Carotid cavernous fistulae (CCFs) are most commonly classified based on arterial supply. Symptomatology and treatment approach, however, are largely influenced by venous drainage. OBJECTIVE: To propose an updated classification system using venous drainage. METHODS: CCFs with posterior/inferior drainage only, posterior/inferior and anterior drainage, anterior drainage only, and retrograde drainage into cortical veins with/without other drainage channels were designated as types 1, 2, 3, and 4, respectively. CCFs involving a direct connection between the internal carotid artery and cavernous sinus were designated as type 5. This system was retrospectively applied to 29 CCF patients. RESULTS: Our proposed classification was significantly associated with symptomatology (P < .001). Type 2 was significantly associated with coexisting ocular/orbital and cavernous symptoms only (P < .001), type 3 with ocular/orbital symptoms only (P < .01), and type 4 demonstrated cortical symptoms with/without ocular/orbital and cavernous symptoms (P < .01), respectively. There was a significant association of our classification system with the endovascular treatment approach (P < .001). Types 1 and 2 were significantly associated with endovascular treatment through the inferior petrosal sinus (P < .01). Type 3 was significantly associated with endovascular treatment through the ophthalmic vein (P < .01) and type 5 with transarterial approach (P < .01), respectively. Types 2 (27.6%) and 3 (34.5%) were most prevalent in this series, whereas type 1 was rare (6.9%), suggesting that some degree of thrombosis is present, with implications for spontaneous resolution. Type 2 CCFs demonstrated a trend toward partial resolution after endovascular treatment (P = .07). CONCLUSION: Our proposed classification system is easily applicable in clinical practice and demonstrates correlation with symptomatology, treatment approach, and outcome. PMID- 26280825 TI - Added Benefit of Stent Retriever Technology for Acute Ischemic Stroke: A Pooled Analysis of the NINDS tPA, SWIFT, and STAR Trials. AB - BACKGROUND: Endovascular treatment is increasingly being used in acute stroke care. However, although stent retrievers show improved flow restoration rates, their clinical benefits have been uncertain. OBJECTIVE: To assess the incremental effect of using stent retrievers compared with intravenous tissue plasminogen activator (IV tPA; alteplase) alone or placebo/control. METHODS: We conducted a pooled analysis of 4 studies using stent retrievers (Solitaire), IV tPA, or placebo/control. We applied the ischemic stroke risk score (www.sorcan.ca/iscore) to each participant to adjust for differences in baseline characteristics. We used a shift analysis to account for the potential benefits across the entire modified Rankin scale score at 90 days, adjusting for time-to-treatment, baseline Alberta Stroke Program Early CT score, and ischemic stroke risk score. RESULTS: Of the 915 participants in this analysis, 312 (34.1%) patients received placebo, 312 (34.1%) received tPA alone, 131 (14.4%) received stent retrievers alone, and 160 (17.5) received combined therapy (IV tPA plus stent retrievers). The shift analysis revealed that more patients remained independent at 90 days if receiving stent retrievers alone (number needed to treat 3.5) or combined with tPA (number needed to treat 3.1) compared with tPA alone. After adjustment, participants receiving stent retrievers alone (odds ratio, 2.95; 95% confidence interval, 1.48 5.89) or combined with tPA (odds ratio, 4.45; 95% confidence interval, 2.40-8.27) were more likely to be independent at 90 days compared with tPA alone. CONCLUSION: Patients with acute ischemic stroke who received IV tPA or revascularization therapies had a higher likelihood of achieving independence at 3 months. Stent retriever technology combined with tPA was associated with the greatest benefit compared with placebo, tPA alone, or endovascular therapy alone. PMID- 26280826 TI - Johann Friedrich Horner and the Repeated Discovery of Oculosympathoparesis: Whose Syndrome Is It? AB - Disruption of cranial sympathetic tone leads to the symptom complex of miosis, ptosis, and hemifacial anhidrosis. It is widely believed that this phenomenon was discovered in 1869 by the Swiss ophthalmologist Johann Friedrich Horner, and as a result, the term Horner syndrome has become synonymous with the clinical presentation. However, the syndrome that would become Horner syndrome had actually been described several times before his report. Francois Pourfour du Petit documented the ocular effects of sympathetic trunk lesions in animal studies in 1727. Claude Bernard identified the full clinical triad in animal studies in 1852, and as a result, the condition is sometimes called Bernard syndrome. There were also 2 previous reports of ptosis and miosis resulting from sympathetic nerve damage in humans: 1 by Edward Selleck Hare in 1838 associated with brachial plexus tumor, and the other by Silas Weir Mitchell in 1864 associated with a gunshot wound to the neck. Although Horner was the first to objectively characterize the co-occurrence of vasomotor and ocular changes in a human patient, he did not identify the etiology of the condition, discuss its relationship to the sympathetic nervous system, or reference any of the previous studies in animals or humans. It is possible that a lack of familiarity with previous investigations delayed the full appreciation of the mechanism underlying this disorder. PMID- 26280828 TI - Response to Journal Club: Real-time Magnetic Resonance-Guided Stereotactic Laser Amygdalohippocampotomy for Mesial Temporal Lobe Epilepsy. PMID- 26280831 TI - Indoor Air Pollution by Methylsiloxane in Household and Automobile Settings. AB - This study examines characteristics of atmospheric methylsiloxane pollution in indoor settings where interior renovation/redecoration is being undertaken, in addition to ordinary family homes and inside family cars. Concentrations of atmospheric methylsiloxane in these locations were approximately one order of magnitude higher than that in outdoor areas. The average indoor concentration of methylsiloxane where renovation was being undertaken was 9.4 MUg/m3, which is slightly higher than that in an ordinary family home (7.88 MUg/m3), while samples from family cars showed lower concentration (3.10 MUg/m3). The indoor atmospheric concentration during renovation/redecoration work was significantly positively correlated with the duration of the work. The structure of atmospheric methylsiloxane pollution is basically the same in these three venues. The concentration of annulus siloxane was much higher than that of linear compounds (85% of the total methylsiloxane concentrations). Household dust in average family homes showed total methylsiloxane concentration of 9.5 MUg/m3 (average); the structure mainly consisted of linear siloxane (approximately 98% of total concentration), thereby differing from that of atmospheric methylsiloxane pollution. The comparatively high concentration of methylsiloxane in these three venues indicates that interior renovation and decoration work, and even travelling in cars, can involve exposure to more serious siloxane contamination during everyday activities. PMID- 26280830 TI - Mathematical Model of Ammonia Handling in the Rat Renal Medulla. AB - The kidney is one of the main organs that produces ammonia and release it into the circulation. Under normal conditions, between 30 and 50% of the ammonia produced in the kidney is excreted in the urine, the rest being absorbed into the systemic circulation via the renal vein. In acidosis and in some pathological conditions, the proportion of urinary excretion can increase to 70% of the ammonia produced in the kidney. Mechanisms regulating the balance between urinary excretion and renal vein release are not fully understood. We developed a mathematical model that reflects current thinking about renal ammonia handling in order to investigate the role of each tubular segment and identify some of the components which might control this balance. The model treats the movements of water, sodium chloride, urea, NH3 and [Formula: see text], and non-reabsorbable solute in an idealized renal medulla of the rat at steady state. A parameter study was performed to identify the transport parameters and microenvironmental conditions that most affect the rate of urinary ammonia excretion. Our results suggest that urinary ammonia excretion is mainly determined by those parameters that affect ammonia recycling in the loops of Henle. In particular, our results suggest a critical role for interstitial pH in the outer medulla and for luminal pH along the inner medullary collecting ducts. PMID- 26280833 TI - Concentrations and Toxic Equivalency of Polychlorinated Biphenyls in Polish Wastewater Treatment Plant Effluents. AB - Wastewater treatment plants (WWTPs) are widely recognized as important sources of toxic contaminants such as polychlorinated biphenyls (PCBs). An example is given in the present paper, where concentrations of 12 dioxin-like PCBs (dl-PCBs) congeners were investigated in effluents from 14 WWTPs of different sizes, using gas chromatography tandem-mass spectrometry. The results obtained demonstrate that the smallest WWTPs are characterized by the highest total dl-PCB concentration of 102.69 pg/L, roughly twice those of medium-size and large WWTPs, i.e. 41.14 and 48.29 pg/L, respectively. In all cases, the concentrations obtained were generated mostly by increased contributions of PCB-77, PCB-105 and PCB-118 which constituted 48 %-59 % of the mean dl-PCB concentration. The results also reveal a predominance of mono-ortho over non-ortho PCBs. All three types of WWTP effluent were found to have similar toxic equivalency (TEQ) values, ranging from 0.31 for large to 0.37 pg TEQ/L for medium WWTPs. PMID- 26280832 TI - Characterization of Fosfomycin Resistant Extended-Spectrum beta-Lactamase Producing Escherichia coli Isolates from Human and Pig in Taiwan. AB - To investigate the efficacy of fosfomycin against extended-spectrum beta lactamases (ESBL) producing Escherichia coli in Taiwan and the resistance mechanisms and characterization of human and pig isolates, we analyzed 145 ESBL producing isolates collected from two hospitals (n = 123) and five farms (n = 22) in Taiwan from February to May, 2013. Antimicrobial susceptibilities were determined. Clonal relatedness was determined by PFGE and multi-locus sequence typing. ESBLs, ampC, and fosfomycin resistant genes were detected by PCR, and their flanking regions were determined by PCR mapping and sequencing. The fosfomycin resistant mechanisms, including modification of the antibiotic target (MurA), functionless transporters (GlpT and UhpT) and their regulating genes such as uhpA, cyaA, and ptsI, and antibiotic inactivation by enzymes (FosA and FosC), were examined. The size and replicon type of plasmids carrying fosfomycin resistant genes were analyzed. Our results revealed the susceptibility rates of fosfomycin were 94% for human ESBL-producing E. coli isolates and 77% for pig isolates. The PFGE analysis revealed 79 pulsotypes. No pulsotype was found existing in both human and pig isolates. Three pulsotypes were distributed among isolates from two hospitals. ISEcp1 carrying blaCTX-M-group 9 was the predominant transposable elements of the ESBL genes. Among the thirteen fosfomycin resistant isolates, functionless transporters were identified in 9 isolates. Three isolates contained novel amino acid substitutions (Asn67Ile, Phe151Ser and Trp164Ser, Val146Ala and His159Tyr, respectively) in MurA (the target of fosfomycin). Four isolates had fosfomycin modified enzyme (fosA3) in their plasmids. The fosA3 gene was harboured in an IncN-type plasmid (101 kbp) in the three pig isolates and an IncB/O-type plasmid (113 kbp) in the human isolate. In conclusion, we identified that 6% and 23% of the ESBL-producing E. coli from human and pigs were resistant to fosfomycin, respectively, in Taiwan. No clonal spread was found between human and pig isolates. Functionless transporters were the major cause of fosfomycin resistance, and the fosA3-transferring plasmid between isolates warrants further monitoring. PMID- 26280834 TI - Determination of TiO2 and AgTiO2 Nanoparticles in Artemia salina: Toxicity, Morphological Changes, Uptake and Depuration. AB - In this study, aquatic stability and toxic effects of TiO2 and AgTiO2 nanoparticles (NPs) were investigated on Artemia salina nauplii. AgTiO2 was found to be more toxic to nauplii compared to TiO2. The mortality rate in nauplii increased significantly with increasing concentrations and duration of exposure. TiO2 eliminations ranged between 27.8% and 96.5% at 50 and 1 mg/L TiO2 exposed to nauplii, respectively. Accumulation and elimination of Ag in AgTiO2 exposed nauplii were similar except at 1 mg/L AgTiO2. When NPs were mixed with water, the hydrodynamic dimensions of NPs significantly increased because of aggregation in saltwater but NP size decreased over time. NPs-exposed nauplii showed changes in eye formation, enlargement of the intestine, malformations in the outer shell and antennae loss were also observed. Since accumulation and toxicity of AgTiO2 NPs was higher than TiO2 alone, inevitably release of AgTiO2 into aqueous environments can cause ecological risks. PMID- 26280835 TI - Association of PCK1 with Body Mass Index and Other Metabolic Features in Patients With Psychotropic Treatments. AB - Weight gain is a major health problem among psychiatric populations. It implicates several receptors and hormones involved in energy balance and metabolism. Phosphoenolpyruvate carboxykinase 1 is a rate-controlling enzyme involved in gluconeogenesis, glyceroneogenesis and cataplerosis and has been related to obesity and diabetes phenotypes in animals and humans. The aim of this study was to investigate the association of phosphoenolpyruvate carboxykinase 1 polymorphisms with metabolic traits in psychiatric patients treated with psychotropic drugs inducing weight gain and in general population samples. One polymorphism (rs11552145G > A) significantly associated with body mass index in the psychiatric discovery sample (n = 478) was replicated in 2 other psychiatric samples (n1 = 168, n2 = 188), with AA-genotype carriers having lower body mass index as compared to G-allele carriers. Stronger associations were found among women younger than 45 years carrying AA-genotype as compared to G-allele carriers (-2.25 kg/m, n = 151, P = 0.009) and in the discovery sample (-2.20 kg/m, n = 423, P = 0.0004). In the discovery sample for which metabolic parameters were available, AA-genotype showed lower waist circumference (-6.86 cm, P = 0.008) and triglycerides levels (-5.58 mg/100 mL, P < 0.002) when compared to G-allele carriers. Finally, waist-to-hip ratio was associated with rs6070157 (proxy of rs11552145, r = 0.99) in a population-based sample (N = 123,865, P = 0.022). Our results suggest an association of rs11552145G > A polymorphism with metabolic related traits, especially in psychiatric populations and in women younger than 45 years. PMID- 26280836 TI - The Effects of BDNF Val66Met Gene Polymorphism on Serum BDNF and Cognitive Function in Methamphetamine-Dependent Patients and Normal Controls: A Case Control Study. AB - Studies suggest that a functional polymorphism of the brain-derived neurotrophic factor gene (BDNF Val66Met) may contribute to methamphetamine dependence. We hypothesized that this polymorphism had a role in cognitive deficits in methamphetamine-dependent patients and in the relationship of serum BDNF with cognitive impairments. We conducted a case-control study by assessing 194 methamphetamine-dependent patients and 378 healthy volunteers without history of drug use on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the presence of the BDNF Val66Met polymorphism and serum BDNF levels. We showed no significant differences in genotype and allele distributions between the methamphetamine-dependent patients and controls. Some aspects of cognitive function significantly differed in the 2 groups. The serum BDNF levels in methamphetamine-dependent patients were significantly higher than those of the healthy controls. In the patients, partial correlation analysis showed a significant positive correlation between serum BDNF and the delayed memory index score. The RBANS scores showed statistically significant BDNF level * genotype interaction. Further regression analyses showed a significant positive association between BDNF levels and the RBANS total score, immediate memory or attention index among Val homozygote patients, whereas a significant negative association of BDNF levels with the RBANS total score, visuospatial/constructional, or language index was found among Met/Val heterozygous patients. We demonstrated significant impairment on some aspects of cognitive function and increased BDNF levels in methamphetamine-dependent patients as well as genotypic differences in the relationships between BDNF levels and RBANS scores on the BDNF Val66Met polymorphism only in these patients. PMID- 26280837 TI - Metformin for Weight Gain and Metabolic Abnormalities Associated With Antipsychotic Treatment: Meta-Analysis of Randomized Placebo-Controlled Trials. AB - This meta-analysis examined the effectiveness and safety of metformin to prevent or treat weight gain and metabolic abnormalities associated with antipsychotic drugs. We systematically searched in both English- and Chinese-language databases for metformin randomized controlled clinical trials (RCTs) using placebo in patients taking antipsychotics. Twenty-one RCTs (11 published in English and 10 in Chinese) involving 1547 subjects (778 on metformin, 769 on placebo) were included in this meta-analysis. Metformin was significantly superior to placebo (standard mean differences, -0.69 to -0.51; P = 0.01-0.0001) in the primary outcome measures (body weight, body mass index, fasting glucose, fasting insulin, triglycerides, and total cholesterol). Metformin was significantly superior to placebo in some secondary outcome measures but not in others. Significantly higher frequencies of nausea/vomiting and diarrhea were found in the metformin group, but no differences were found in other adverse drug reactions. In the metformin group, the frequency of nausea/vomiting was 14%, and of diarrhea, 7%. Subgroup and sensitivity analyses demonstrated that primary outcomes were influenced by ethnicity, treatment style (intervention vs prevention), metformin dose, study duration, and mean age. Body weight standard mean difference was 0.91 (confidence interval [CI], -1.40 to -0.41) in 3 prevention RCTs in naive patients, -0.66 (CI, -1.02 to -0.30) in 5 intervention RCTs during the first year, and -0.50 (CI, -0.73 to -0.27) in 9 intervention RCTs in chronic patients. This meta-analysis suggests that adjunctive metformin is an effective, safe, and reasonable choice for antipsychotic-induced weight gain and metabolic abnormalities. PMID- 26280839 TI - Are traits useful? Explaining trait manifestations as tools in the pursuit of goals. AB - Traits and motivation mainly have been treated separately for almost a century. The purpose of these studies is to test the proposal that traits and motivation are intricately linked. Specifically, that 1 explanation for traits, at least in terms of their descriptiveness of what people actually do, is the goals people pursue. Study 1 used experience-sampling methodology to show that almost half the variance in extraversion and conscientiousness manifestation was explained by goal pursuit differences. Both why people enacted more of extraversion and/or conscientiousness than others, and why people enacted extraversion and/or conscientiousness at any given moment were explained by the goals people were pursuing at those moments. Study 2 used experimental methodology to show that extraversion and conscientiousness enactment was in fact caused by the goal pursuit. Study 3 employed observer ratings to show that the goal-dependent enactments of traits were observer-verified actual behaviors. In all 3 studies, different goals affected different traits discriminatively. Thus, these findings provided strong evidence for 1 explanation of traits, that they are useful for accomplishing goals. These findings provided 1 answer to long-standing questions about the conceptual relations between traits and motivation. And these findings clarified the meaning and nature of extraversion and conscientiousness by revealing part of what these traits are for. PMID- 26280838 TI - Daily physical activity and life satisfaction across adulthood. AB - Physical activity is considered a valuable tool for enhancing life satisfaction. However, the processes linking these constructs likely differ across the adult life span. In older adults the association between physical activity and life satisfaction appears to involve usual levels of physical activity (i.e., a between-person association driven by differences between more and less active people). In younger adults the association has consistently been based on day-to day physical activity (i.e., a within-person association driven by differences between more and less active days). To resolve this inconsistency, a daily diary study was conducted with a life span sample of community-dwelling adults (age 18 89 years; N = 150) over three 21-day measurement bursts. Usual physical activity was positively associated with life satisfaction in middle and older adulthood; however, this association was not present in young adulthood. When present, this between-person association was mediated by physical and mental health. A within person association between physical activity and life satisfaction was also present (and did not differ across age). Generally, on days when people were more physically active then was typical for them, they experienced greater life satisfaction. Age differences in life satisfaction followed a cubic trajectory: lower during emerging adulthood, higher during midlife, and lower during older adulthood. This study adds to accumulating evidence that daily fluctuations in physical activity have important implications for well-being regardless of age, and clarifies developmental differences in life satisfaction dynamics that can inform strategies for enhancing life satisfaction. PMID- 26280840 TI - Affective contingencies in the affiliative domain: Physiological assessment, associations with the affiliation motive, and prediction of behavior. AB - According to classical motive disposition theory, individuals differ in their propensity to derive pleasure from affiliative experiences. This propensity is considered a core process underlying the affiliation motive and a pervasive cause of motivated behavior. In this study, we tested these assumptions. We presented participants with positive affiliative stimuli and used electromyography to record changes in facial muscular activity that are indicative of subtle smiling. We were thus able to physiologically measure positive affect following affiliative cues. Individual differences in these affective contingencies were internally consistent and temporally stable. They converged with affiliation motive self- and informant reports and picture story exercise scores, indicating that they are partly accessible to the self, observable to outsiders, and overlap with implicit systems. Finally, they predicted affiliative behavior in terms of situation selection and modification across a wide variety of contexts (i.e., in daily life, the laboratory, and an online social network). These findings corroborate the long-held assumption that affective contingencies represent a motivational core aspect of affiliation. PMID- 26280841 TI - Social responses to expressive suppression: The role of personality judgments. AB - Why do people who suppress their emotion-expressive behavior have difficulty forming close, supportive relationships? Previous studies have found that suppression disrupts the dynamics of social interactions and existing relationships. We evaluated a complementary hypothesis: that suppression functions as a behavioral cue leading others to form negative personality impressions of suppressors, even at zero-acquaintance. In 2 studies, participants reported personality judgments and other impressions of targets who either suppressed or expressed their emotion-expressive behavior in response to amusing or sad film clips. In findings replicated across studies, targets who suppressed either amusement or sadness were judged as less extraverted, less agreeable, and more interpersonally avoidant and anxious than targets who expressed emotions, and participants were less interested in affiliating with suppressors compared with expressers. Effects were amplified when targets suppressed amusement (compared with sadness) and when participants knew the emotional context (compared with when they did not) and, thus, could form expectations about what emotions targets should be showing. Extraversion and agreeableness judgments mediated the effect of suppression on participants' disinterest in affiliating. In Study 2, which extended Study 1 in several ways, effects were pronounced for the enthusiasm aspect of extraversion and the compassion aspect of agreeableness. We also found evidence that judgments of suppressors do not simply fall between neutral and fully expressing targets; rather, judgments of suppressors are qualitatively different. We discuss implications for understanding the social consequences of emotion regulation-in particular, how beyond disrupting relationships, suppression may prevent some relationships from even forming in the first place. PMID- 26280842 TI - When bias binds: Effect of implicit outgroup bias on ingroup affiliation. AB - We tested a novel process we term implicit homophily in which perceivers' implicit outgroup bias shapes their affiliative responses toward ingroup targets with outgroup friends as a function of perceived similarity. Across 4 studies, we tested implicit homophily in the context of racial groups. We found that White participants with higher implicit anti-Black bias reported less affiliative responses toward White targets with Black friends compared with White targets with White friends, and this effect persisted above and beyond the effects of implicit pro-White bias and explicit racial bias (Studies 1-3). We further found evidence that this relationship between implicit anti-Black bias and affiliation exists because participants infer how comfortable targets are around outgroup members (Preliminary Study) and use this information to infer similarity on this dimension (Studies 1-3). Our findings also suggested that stigma transference and expectancy violation were not viable alternative mediators (Preliminary Study and Study 1). Finally, women's implicit anti-Black bias predicted their likelihood of having Facebook friends with Black friends, providing ecological and behavioral evidence of implicit homophily (Study 4). Implications for research on stigma by association, extended contact, affiliation, and network formation are discussed. PMID- 26280843 TI - Correction to Carey et al. (2015). PMID- 26280846 TI - Bimetallic Complexes Supported by a Redox-Active Ligand with Fused Pincer-Type Coordination Sites. AB - The remarkable chemistry of mononuclear complexes featuring tridentate, meridionally chelating "pincer" ligands has stimulated the development of ligand frameworks containing multiple pincer sites. Here, the coordination chemistry of a novel pentadentate ligand (L(N3O2)) that provides two closely spaced NNO pincer type compartments fused together at a central diarylamido unit is described. The trianionic L(N3O2) chelate supports homobimetallic structures in which each M(II) ion (M = Co, Cu, Zn) is bound in a meridional fashion by the bridging diarylamido N atom and O,N-donors of the salicyaldimine arms. The metal centers are also coordinated by a mono- or bidentate auxiliary ligand (L(aux)), resulting in complexes with the general form [M2(L(N3O2))(L(aux))2](+) (where L(aux) = 1 methyl-benzimidazole (1MeBI), 2,2'-bipyridine (bpy), 4,4'-dibromo-2,2'-bipyridine (bpy(Br2)), or (S)-2-(4-isopropyl-4,5-dihydrooxazolyl)pyridine (S-(iPr)OxPy)). The fused nature of the NNO pincer sites results in short metal-metal distances ranging from 2.70 A for [Co2(L(N3O2)) (bpy)2](+) to 3.28 A for [Zn2(L(N3O2)) (bpy)2](+), as revealed by X-ray crystallography. The complexes possess C2 symmetry due to the twisting of the aryl rings of the MU-NAr2 core; spectroscopic studies indicate that chiral L(aux) ligands, such as S-(iPr)OxPy, are capable of controlling the helical sense of the L(N3O2) scaffold. Since the four- or five coordinate M(II) centers are linked solely by the amido moiety, each features an open coordination site in the intermetallic region, allowing for the possibility of metal-metal cooperativity in small-molecule activation. Indeed, the dicobalt(II) complex [Co2(L(N3O2)) (bpy(Br2))2](+) reacts with O2 to yield a dicobalt(III) species with a MU-1,2-peroxo ligand. The bpy-containing complexes exhibit rich electrochemical properties due to multiple metal- and ligand-based redox events across a wide (3.0 V) potential window. Using electron paramagnetic resonance (EPR) spectroscopy and density functional theory (DFT), it was determined that one-electron oxidation of [Co2(L(N3O2)) (bpy)2](+) results in formation of a S = 1/2 species with a L(N3O2)-based radical coupled to low-spin Co(II) centers. PMID- 26280844 TI - Sortase A Inhibitors: Recent Advances and Future Perspectives. AB - Here, we describe the most promising small synthetic organic compounds that act as potent Sortase A inhibitors and cater the potential to be developed as antivirulence drugs. Sortase A is a polypeptide of 206 amino acids, which catalyzes two sequential reactions: (i) thioesterification and (ii) transpeptidation. Sortase A is involved in the process of bacterial adhesion by anchoring LPXTG-containing proteins to lipid II. Sortase A inhibitors do not affect bacterial growth, but they restrain the virulence of pathogenic bacterial strains, thereby preventing infections caused by Staphylococcus aureus or other Gram-positive bacteria. The efficacy of the most promising inhibitors needs to be comprehensively evaluated in in vivo models of infection, in order to select compounds eligible for the treatment of bacterial infections in humans. PMID- 26280845 TI - Effects of Nanoparticle Size on Multilayer Formation and Kinetics of Tethered Enzymes. AB - Despite numerous applications, we lack fundamental understanding of how variables such as nanoparticle (NP) size influence the activity of tethered enzymes. Previously, we showed that biomimetic oriented immobilization yielded higher specific activities versus nonoriented adsorption or carboxyl-amine binding. Here, we standardize NP attachment strategy (oriented immobilization via hexahistidine tags) and composition (Ni-NTA coated gold NPs), to test the impact of NP size (?5, 10, 20, and 50 nm) on multilayer formation, activity, and kinetic parameters (kcat, KM, kcat/KM) of enzymes representing three different classes: glucose-6-phosphate isomerase (GPI), an isomerase; Glyceraldehyde-3-phosphate dehydrogenase S (GAPDHS), an oxidoreductase; and pyruvate kinase (PK), a transferase. Contrary to other reports, we observed no trend in kinetic parameters for individual enzymes when found in monolayers (<100% enzyme coverage), suggesting an advantage for oriented immobilization versus other attachment strategies. Saturating the NPs to maximize activity per NP resulted in enzyme multilayer formation. Under these conditions, total activity per NP increased with increasing NP size. Conversely, specific activity for all three enzymes was highest when tethered to the smallest NPs, retaining a remarkable 73 94% of the activity of free/untethered enzymes. Multilayer formations caused a clear trend of kcat decreasing with increasing NP size, yet negligible change in KM. Understanding the fundamental relationships between NP size and tethered enzyme activity enables optimized design of various applications, maximizing activity per NP or activity per enzyme molecule. PMID- 26280847 TI - Arthroscopy in knee osteoarthritis: a systematic review of the literature. AB - Knee arthroscopy has historically been a common treatment for knee osteoarthritis. A Cochrane review of the literature up to 2006 has resulted in guidance that arthroscopy is not effective in knee osteoarthritis. It cited that deficiencies in the evidence base prevented widespread acceptance of the recommendations. The aim of this review is to update the evidence base for the efficacy of arthroscopy in knee osteoarthritis. The authors searched CINHAL, EMBASE, MEDLINE, and CENTRAL for randomised controlled trials that compared arthroscopic surgery in knee osteoarthritis with a control group (e.g. lavage, best medical care). The primary outcome measure was patient reported functional outcome. The study methodology was registered on Prospero, a systematic review register: Registration number CRD42012002891. Five randomised controlled trials included 516 patients, almost double the 271 episodes contained in previous reviews. Two high quality studies, according to the Jadad classification, published since the Cochrane review, addressed many of the methodological flaws criticised in previous reviews. However, certain subgroup analyses (e.g. patients with meniscal tears and mechanical symptoms) are still underpowered. PMID- 26280848 TI - Fixation of the greater tuberosity in proximal humeral fractures: FiberWire(r) or wire cerclage? AB - Proximal humeral fractures remain a surgical challenge, and scientific discussions are commonly focused on their ideal treatment. One possible treatment involves the use of an angle stable plate osteosynthesis. However, which material can most feasibly be used to attach the greater tuberosity to the implant remains unknown. In two prospective, non-randomized trials, we compared the results of a FiberWire(r) and a wire cerclage. A total of 104 patients with 3- and 4-part fractures were included in this examination. In 25 cases, the greater tuberosity was fixated with a FiberWire(r), size 2, while 79 cases received a wire cerclage. Plate osteosynthesis was constantly performed via the anterolateral delta-split approach using the NCB(r)-PH-plate by Zimmer(r). The patients were followed clinically at discharge, 6 weeks and 6 months postoperatively and were examined for relevant complications. Age and gender were equally distributed in both groups. Concerning the follow-up after 6 weeks, a significant benefit concerning shoulder function was observed in the FiberWire(r)-group (wire cerclage: 39.20+/ 11.85, 95% CI 32.37-44.56, FiberWire(r): 45.84+/-16.80, 95% CI 28.34-61.56: p=0.049). After 6 months, the difference between the groups was not significant (wire cerclage: 58.13+/-18.73, 95% CI 50.25-72.40, FiberWire(r): 68.85+/-23.10, 95% CI 46.83-99.53: p=0.06). PMID- 26280849 TI - Treatment of large diaphyseal bone defect of the tibia by the "fibula pro tibia" technique: application in developing countries. AB - Large segmental bone defects of the tibia may be due to infections, high-energy fractures, congenital diseases or tumors and represent a challenge for both the physician and the patient. In developing countries, the use of expansive techniques is not possible so that amputation is sometimes proposed. However, an alternative technique for limb salvage, applicable in developing countries consists of tibialization of the ipsilateral fibula. This technique is also called "Fibula pro Tibia", fibular transfer to the tibia or fibular centralization. We report this transfer in 4 patients with an average defect length of 11.8 cm. Union between the transferred fibula and the tibia was obtained in all patients, for both proximal and distal junctions, after an average time of 8.5 months (range, 4 to 18 months). Three patients returned to a normal walking function while one was still limping, but was able to walk independently without need of crutches. PMID- 26280850 TI - Use of Calscan for improving osteoporosis care in the older patient admitted with hip fracture. AB - To determine whether bone mineral density measurement using the Calscan successfully predicts the actual bone mineral density, as measured by dual-energy X-ray absorptiometry. We included all patients>=65 years with a hip fracture screened on osteoporosis by both dual-energy X-ray absorptiometry and the Calscan during the period April 2008 to April 2011. The bone mineral density was expressed as a T-score. For the Calscan T-score, thresholds were defined such that patients with and without osteoporosis could be identified with 90% certainty. Patients with a Calscan T-score above the upper threshold were considered to be non-osteoporotic and those with a Calscan T-score below the lower threshold considered osteoporotic. Patients whose Calscan T-score lay between the two thresholds could only be classified by means of DXA. The correlation between dual-energy X-ray absorptiometry and the Calscan was 0.61. The Calscan identified approximately 25% of patients as osteoporotic and 25% as non-osteoporotic. The upper threshold was found to be -1.8SD and the lower threshold -3.5SD. Osteoporosis screening by dual-energy X-ray absorptiometry had been carried out in 44% of patients. This percentage could theoretically rise to >70% if the Calscan is implemented in osteoporosis screening, while costs of such screening appear to be lower, as long as a sufficient number of patients are screened. PMID- 26280851 TI - Clinical results of cementless total hip arthroplasty with shortening osteotomy for high dislocation with developmental dysplasia. AB - Total hip arthroplasty for severe developmental dysplasia of the hip is a technically challenging procedure. Subtrochanteric femoral osteotomy enables reducing the femoral head and restoring abductor muscle strength without compromising proximal femoral bone stock in advanced dysplasia.We aimed to retrospectively evaluate Crowe type III or IV developmental dysplasia of the hip who underwent reconstruction with cementless total hip arthroplasty combined with a transverse subtrochanteric femoral osteotomy. Sixty hips of 52 patients (11 male, 49 female) with Crowe type III (n: 37) or IV (n: 23) developmental dysplasia of the hip were included. The average age was 51.4 years. Surgery was performed in lateral decubitis position with posterolateral approach. Subtrochanteric transverse femoral osteotomy were used with cementless components. 40 of the femoral components were Secur-Fit type, and 20 of them were secur-fit plus max type. Ceramic-ceramic coupling was used in 24 cases and metal polyethylene coupling was used in 36 cases. Merle D'Aubigne and Harris Hip score were used to rate the clinical outcome at the final follow up. All femoral shortening osteotomies were united at a mean of 5.7 months. Mean Merle D'Aubigne pain score was increased from 3.1 to 5.4, and mean Harris Hip score improved from 39 to 92.8, postoperatively (p<0.01). There was no significant difference in time to union between different types of stems. 4 femoral stems had asymptomatic radiolucent lines. There was no significant difference in time to union between different types of stems. PMID- 26280852 TI - Association between the capitate-triquetrum distance and carpal collapse in scaphoid nonunion. AB - The effect of the lunate type on carpal collapse in cases of scaphoid nonunion has not been thoroughly investigated. The purpose of the present study was to determine whether any association exists or not between the capitate-triquetrum distance and occurrence of carpal collapse in cases of scaphoid nonunion. In a retrospective study, 76 patients with scaphoid nonunion formed two groups based on the capitate-triquetrum distance: forty-three patients with distance of less than 5 mm and 33 patients with distance of 5 mm or more. The two groups were comparable with respect to sex distribution, age, dominant hand involvement, manual labor, nonunion location and time from injury to final x-rays. Six patients (13.9%) in the capitate-triquetrum<5 mm group and 13 patients (39.4%) in the capitate-triquetrum>=5 mm group had no signs of collapse, with significant difference (p<0.05). Capitate-triquetrum distance could contribute in the decision making process for cases of scaphoid nonunion without straightforward indication for surgical intervention. PMID- 26280853 TI - Effects of body mass index, infrapatellar fat pad volume and age on patellar cartilage defect. AB - The aim of this study was to evaluate the associations between patellar cartilage defects and body mass index (BMI), infrapatellar fat pad (IPFP) volume and age. 100 patients who met the inclusion criteria and were aged 18 to 60, were evaluated retrospectively. For detecting and measuring patellar cartilage defects, axial sequences were used and sagittal sequences were used to evaluate IPFP volumes. In total, 40 patients had patellar cartilage defects. In this group, age and BMI were higher in both sexes when compared with the controls (p<0.05). The IPFP volume was lower in the group with the patellar cartilage defect when compared with the control group (p<0.05). The IPFP volume was statistically significantly lower in women (p<0.05). Patellar cartilage defect was found to be related to age and BMI. In women, the decrease in IPFP volume seems to be one of the causative factors for patellar cartilage defect. PMID- 26280854 TI - Intra- and periarticular osteoid osteoma: Percutaneous destruction and alcoholisation. AB - Intra- or periarticular osteoid osteoma (00) is uncommon, and therefore a diagnostic challenge. Symptoms are: chronic synovitis, decreased range of motion, joint effusion, and joint contracture. Radiographically, the classical perifocal sclerotic margin is often absent, which leads to a significant delay in diagnosis. The authors retrospectively studied 50 cases of intra- and peri articular OO, treated with percutaneous destruction and alcoholisation. The mean follow-up period was 8.7 years (range, 1 to 15 years). The diagnosis was only made after +/-14 months (range, 8 to 18 months), due to atypical symptoms (nightly pain absent in 38%) and uselessness of plain radiographs (in 100%). CT scan, contrast enhanced MRI and bone scan brought the solution. The technique was successful in 48 out of 50 cases (96%): incomplete excision occurred in 2 patients. The diagnosis of intra- or periarticular OO should be considered in case of unexplained joint pain where conservative treatment is inefficient. PMID- 26280855 TI - Short versus standard duration tourniquet use during Total Knee Replacement: A pilot study. AB - We performed a prospective, randomized, controlled trial to know whether a short duration of tourniquet application affects surgical time, post-operative swelling, pain, early rehabilitation and complications compared to standard use of tourniquet throughout the procedure. Sixty knees were randomized. There were no differences in terms of surgical time and pain experienced between the two groups. Patients in the short duration tourniquet group had significantly less thigh swelling (3.7+/-1.6 versus 4.8+/-2.35 p<0.01). There were no differences in the early rehabilitation between the groups. Soft tissue complications were higher in standard duration group. The use of tourniquet only during cementation of the implants reduces the thigh swelling and soft tissue complications associated with tourniquet use throughout the procedure. PMID- 26280856 TI - The modified scarf osteotomy in the treatment of tailor's bunion: midterm follow up. AB - The aim of this study was to present the midterm results of modified scarf osteotomy in the treatment of tailor's bunion. From 2004 to 2011, 23 modified scarf osteotomies (with the fifth metatarsal shortening) were performed in group of 18 patients for the treatment of tailor's bunion. The mean follow-up period was 58.8 (range: 24-89) months. Patients were evaluated retrospectively- clinically and radiographically, using the American Orthopaedic Foot & Ankle Society scoring system with weight-beared radiographs at the end of 2013. Five males and thirteen females (mean age: 46.5 years) were included in the study. Two males and three females were operated bilaterally. Average American Orthopaedic Foot & Ankle Society scores were 59.8 preoperatively and 92.3 at the final follow up. Three patients had complications: delayed union, superficial wound infection and distal screw migration. The modified scarf osteotomy in the correction of tailor's bunion offers promising results in the midterm. PMID- 26280857 TI - Dorsal nail plate versus percutaneous k-wire fixation in the treatment of displaced distal radius fractures. AB - Distal radius fractures are the most common fractures in the elderly, yet the treatment is controversial and still debated in the literature. Twenty four patients aged older than sixty with distal radial fractures were treated by dorsal nail plate. We compared them with twenty four similar matched patients treated by percutaneous Kirschner wiring surgical method. The patients were operated on by a surgeon experienced in carrying out hand surgery. The purpose of this retrospective review was to compare the clinical and radiological outcomes in elderly patients with displaced distal radial fractures who were treated with either the dorsal nail plate or percutaneous Kirschner wiring surgical procedures. Both groups had high union rates and low complication rates for the treatment of displaced distal radius fractures in elderly patients. However, better functional results can be expected in dorsal nail plate. PMID- 26280858 TI - Review of quality of x-rays for templating for total hip arthroplasty. AB - Digital templating of x-rays for total hip arthroplasty is used routinely for pre operative planning. This is to assure that appropriately sized implants are selected to replicate patient's hip biomechanics. Multiple studies have shown that templating does not always correspond to the final implants used. The aim of this study was to assess the suitability of the x-rays taken pre-operatively for templating for total hip arthroplasty. We undertook a review of a series of pre operative templating pelvis x-rays in 100 consecutive patients undergoing total hip arthroplasty. These x-rays were compared against set criteria to determine their suitability for use for templating. We determined that six x-rays met the criteria whereas ninety four x-rays did not meet the criteria for suitable x rays. Twenty patients had repeat x-rays. The reasons for unsuitability were inadequate opposite femur (66%), absence or incomplete template (54%), inadequate femur length (47%), external rotation (39%), absence of opposite hip (4%). The twenty repeated x-rays were also reviewed for the same parameters and two (10%) satisfied the established criteria. It is imperative that x-rays for templating for total hip arthroplasty are done to a strict standard to obtain an x-ray that is appropriate for templating and there is minimal exposure of the patient to irradiation. PMID- 26280859 TI - Endo medullary extractability of cementless full HA coated femoral stem: Results from 19 cases. AB - The Aura cementless full HA coated stem is an anatomical femoral component with a different surface treatment in the metaphyseal and diaphyseal areas. We have studied the feasibility of isolated endo-medullar extraction of the stem. 19 patients (6 infections, 6 neck fractures, 3 stems with risk of fracture, 3 head fractures, and 1 recurrent dislocation) were subjected to the removal of a stable and bone integrated implant at a mean of 4.5 years after surgery. The 19 cases represent the entire population of Aura cementless integrated stem requiring revision during the period of 2003 through 2011, excluding periprosthetic bone fracture cases. The technique consisted of a careful release of the metaphyseal part of the implant with thin osteotomes, followed by the use of a highly efficient extractor. The re-implanted procedure always utilised standard stems: 17 cementless stems full HA coated (13 had the same size as the removed implant, 4 cases had larger sizes) and two received cemented stems. The 19 stems were extracted by simple endo-medullary approach, without the need for additional action. Several complications were encountered, 1 intraoperative diaphyseal fracture, requiring a wiring, 1 fracture of the lesser trochanter at 15 days post surgery, requiring a revision and 2 postoperative dislocations. Except for the early revision due to fracture, no other stem was revised. There was no recurrence of infection and the functional results were satisfactory (PMA 15-18). 3 patients showed metaphyseal lucent lines on X-Ray leading us to advise the use of a standard stem with larger size after distal reaming, combined with preventive circulate of the calcar. The use of dedicated instrumentation allows successful extraction of full HA coated short stem by endomedullary approach. PMID- 26280860 TI - MRI following UKA: The component-bone interface. AB - BACKGROUND: Loosening is one of the major long-term failure modes in unicondylar knee arthroplasty (UKA). The aim of the study is to describe and characterize implant-bone interface of femoral and tibial components after UKA by means of magnet resonance imaging (MRI). MATERIAL AND METHODS: MRI tailored to reduce metallic artefact of the knee after medial UKA was performed in 10 patients as a pilot study. The component-bone interface at femoral and tibial components was evaluated by two independent investigators. They gave degree of confidence to their evaluation of each parameter on a five-point scale. Inter-observer reliability was determined. RESULTS: Artefacts provoked by the implants were rare. Inter-observer reliability and confidence were excellent for the femoral interface. They were lower at the tibial interface but results were still satisfactory. CONCLUSIONS: Tailored MRI allows reproducible analysis of the component-bone interface after UKA. It is helpful in assessment of suspected loosening after UKA. PMID- 26280861 TI - Sport and physical activity in patients after derotational corticotomies with the Ilizarov method. AB - BACKGROUND: Torsional distortion causes numerous musculoskeletal pathologies. Effective treatment allows restoring limb function and return to sport activity. Objectives was to assess the sport activity in patients with derotational corticotomies using the Ilizarov method. METHODS: It was case series retrospective study. The study examined 56 patients. The control group consisted of 54 patients. A mean follow-up time was 5 years and 6 months. A mean age at the start of treatment was 19 years and 10 months. Patients underwent derotational corticotomies of distal epiphysis of the femur or proximal epiphysis of the tibia using the Ilizarov method. The effect of etiology, type of treatment strategy, and rate, size, and level of derotation on the scores of four activity scales was evaluated; additionally, the activity was compared with the control group. RESULTS: There were no differences in the scales of activity before and after treatment in the study and control groups. In the study group, higher activity after treatment was reported in the level of GRIMBY activity. Patients with internal torsion had a higher VAS activity level after treatment as compared to patients with external torsion. CONCLUSIONS: Derotational corticotomies allow returning to or increasing physical and sport activity: they do not have a negative influence on physical activity after treatment as compared to the control group. PMID- 26280862 TI - A minimum three-year clinical and radiological follow up of the utilisation of a Cementless Multihole Mega cups in conversion hip arthroplasty--a prospective analysis. AB - The introduction of multihole mega cup has proposed innovative answers in the management of acetabular impediments that ensued from the use of bipolar hemiarthroplasty. This study bestows a prospective analysis of the outcome of conversion surgery from bipolar hemiarthroplasty to total hip replacement in patients with acetabular complications.Forty-two patients, 22 men and 20 women, with a mean age of 59 years (range 46-69 years) who experienced complex acetabular deficiencies following bipolar hemiarthroplasty, were converted to total hip replacement between January 2008 and June 2010. Pain was the main complaint in all cases. It was primarily confined to the groin region. Limping due to shortening of the affected limb was the second main complaint (30 cases). All cases had erosion of the acetabulum with varying degrees of protrusion. Cementless mutihole cups with augmentation by autogenous bone graft from the iliac crest and large metal heads' sizes were used for conversion in all cases. After a minimum follow-up of 36 months, Harris hip scores (HHS) improved from a mean of 36.8+/-6.8 (range 21-59) preoperatively to a mean of 85.9+/-5.6 (range 71 to 94) postoperatively. Thirty six (85.7%) patients experienced no groin pain postoperatively while six patients (14.3%) described limited improvement. Postoperative complications included: dislocation in two cases which were reduced and did not result in a poor outcome later on. No patients were lost to follow up. CONCLUSIONS: Short-term results at minimum three years follow-up of multihole mega cup were encouraging regarding high capability of acetabular reconstruction with less morbidity of recipient site. Significant pain and functional improvement were noticeable, however further longer term studies are consequently recommended. PMID- 26280863 TI - Is conservative treatment still defensible in grade III acromioclavicular dislocation? Are there predictive factors of poor outcome? AB - The optimal treatment of grade III acromioclavicular (AC) dislocation is still controversial. Recent studies recommend surgery at that stage whereas meta analysis favours conservative management. The objective of the present investigation was to analyse a clinical series of non-operated grade III AC dislocations and to determine their functional status. Thirty-five patients treated conservatively with a grade III acromioclavicular dislocation were retrospectively reviewed. Simple shoulder test, Oxford shoulder and bilateral Constant shoulder score were used for assessment. Various predictive criteria of poor outcome, particularly scapular dyskinesis were taken into account for analysis. Overall mean and median Constant Score of the injured side were 92.9 and 94, whilst the contralateral shoulder values were respectively 94.9 and 95 (mean and median scores). Ten patients had scapular dyskinesis. Laterality, shoulder activity and scapular dyskinesis were not statistically related to worse outcome. Twenty-eight (80%) patients resumed normal activity within six months. All but two patients were subjectively very satisfied or satisfied. Conservative treatment provided satisfactory results whatever the shoulder activity. No risk factors were predictive of a poorer outcome. Conservative management should remain the first option to manage these injuries. PMID- 26280864 TI - Sample size calculations in orthopaedics randomised controlled trials: revisiting research practices. AB - The purpose of this study was to identify how often sample size calculations were reported in recent orthopaedic randomized controlled trials (RCTs) and to determine what proportion of studies that failed to find a significant treatment effect were at risk of type II error. A pre-defined computerized search was performed in MEDLINE to identify RCTs published in 2012 in the 20 highest ranked orthopaedic journals based on impact factor. Data from these studies was used to perform post hoc analysis to determine whether each study was sufficiently powered to detect a small (0.2), medium (0.5) and large (0.8) effect size as defined by Cohen. Sufficient power (1-beta) was considered to be 80% and a two tailed test was performed with an alpha value of 0.05. 120 RCTs were identified using our stated search protocol and just 73 studies (60.80%) described an appropriate sample size calculation. Examination of studies with negative primary outcome revealed that 68 (93.15%) were at risk of type II error for a small treatment effect and only 4 (5.48%) were at risk of type II error for a medium sized treatment effect. Although comparison of the results with existing data from over 10 years ago infers improved practice in sample size calculations within orthopaedic surgery, there remains an ongoing need for improvement of practice. Orthopaedic researchers, as well as journal reviewers and editors have a responsibility to ensure that RCTs conform to standardized methodological guidelines and perform appropriate sample size calculations. PMID- 26280865 TI - A comparative study of less invasive stabilization system and titanium elastic nailing for subtrochanteric femur fractures in older children. AB - The objective of this study was to compare prospectively the complications and the radiographic and clinical outcomes of reverse less invasive stabilization system (LISS) and titanium elastic nailing (TEN) for the treatment of subtrochanteric femur fractures in older children. From April 2004 to February 2012, 52 children aged from 10 to 15 years old with subtrochanteric fractures were included in this study. 26 patients were treated with reverse LISS (LISS group) and 26 children treated with titanium elastic nails (TEN group) respectively. Perioperative care was standardized. Surgical time, blood loss, length of hospitalization, hospital costs, fracture union time, full weight bearing time and complications were analyzed. The radiologic results as well as hip functional outcomes were evaluated. The average follow-up time of LISS group was 36.5+/-9.3 months and TEN group was 40.2+/-10.6 months. No significant difference between these two groups was found in union time, full weight-bearing time and average length of hospitalization. However, the patients of LISS group had longer operation time (60.0+/-10.6 min vs. 40.5+/-7.4 min, p<0.01), more blood loss (130.0+/-45.0 ml vs. 15.5+/-10.2 ml, p<0.01), and more hospital costs (25000+/-700 RMB vs. 10800+/-500 RMB, p<0.01). The overall complication rate was significantly higher in the LISS group than in the TEN group (12/26 vs. 5/26, p=0.039). There was no significant difference between the two groups in terms of early and late radiological results. Using the Sanders score system, there were 13 excellent, 6 good and 7 fair results in the LISS group compared with 22 excellent and 4 good results in the TEN group. The excellent and good rate was significantly different between the two groups (p=0.010). Our results indicated that TEN fixation of subtrochanteric femur fractures in older children was associated with better function scores and a lower overall complication rate when compared with reverse LISS. PMID- 26280866 TI - Functional outcome following primary total knee arthroplasty cannot be predicted using the initial post-operative radiograph. AB - Obtaining standardised post-operative radiographs following total knee arthroplasty is common practice. Little is known regarding how measurements taken from the initial post-operative radiograph correlate to functional outcome. The initial post-operative radiographs for 110 primary total knee arthroplasties were reviewed retrospectively. Femoral and tibial component alignment was measured by two independent consultant radiologists. Functional outcome was assessed by the Oxford Knee Score pre-operatively and one year post-operatively. Correlation was determined by Pearson correlation analysis. There was no significant correlation between the radiographic measurements with the one year post-operative Oxford Knee Score nor was there significant correlation with the difference in pre operative and post-operative scores. The initial post-operative radiograph cannot be used as a tool to reliably predict functional outcome at one year. PMID- 26280867 TI - Arthroscopic treatment of avulsed tibial spine fractures using a transosseous sutures technique. AB - Severely displaced tibial spine fractures should be treated surgically to restore joint congruity and cruciate integrity with reduction and fixation through an arthrotomy or arthroscopic techniques. Arthroscopy is preferred as it allows for accurate diagnosis and treatment of associated injuries and reduction and fixation of all types of tibial spine fractures while reducing the morbidity associated with open techniques. We report the clinical and radiographical results of 11 cases treated with a technique of arthroscopic internal fixation with non-absorbable sutures, after an average follow-up of 16.3 months (range, 11 to 21 months). The clinical examination using the IKDC system revealed all patients to have a negative Lachman test and no quadriceps weakness except one patient with some laxity (hard end 1+ Lachman test). One patient had a minor extension deficit of approximately 5 degrees . The other patients showed a full range of motion without extension loss. This technique is simple, reproducible and very useful in dealing with these fractures. PMID- 26280868 TI - Anterior transfer of tibialis posterior tendon for treating drop foot: Technique of enforcing tendon implantation to improve success rate. AB - An absolutely convincing technique of anterior transfer of the tibialis posterior (TP) tendon for treating drop foot has not been developed. Thirty-seven consecutive adult patients with drop foot owing to deep peroneal nerve injury were treated with bone-to-bone TP tendon transfer. The TP tendon with a small bony attachment was procured from the undersurface of the navicula and then transferred through a tunnel of the interosseous membrane. The navicular attachment was implanted in the tunnel of the navicula or intermediate cuneiform. Cancellous bone graft procured from the distal tibial metaphysis was packed into the tunnel inlet. Side-to-side tendon suturing was performed between the TP tendon and tibialis anterior tendon. Thirty-one patients were followed for a mean of 2.8 years (range, 1.2-4.8 years), and all achieved satisfactory outcome for the ankle. All patients achieved a normal gait after one year and at the latest follow-up. CONCLUSIONS: The described technique may provide a high success rate. This surgical technique is not complex, and complications are few. PMID- 26280869 TI - Isolated subtalar arthrodesis. AB - The aim of this study is to review the results of isolated subtalar arthrodesis in adults and to make a comparative analysis of the clinical outcomes between the patients with posttraumatic subtalar arthritis and the ones with other etiologic factors, and to evaluate the effects of grafting. This study included 19 men and 12 women. The mean postoperative follow-up was 36.8 months. The mean AOFAS hindfoot score improved from a mean of 46 preoperatively to a mean of 77.3 postoperatively. Thirty-one of 33 arthrodeses achieved bony union at a mean time of 15.7 weeks. The mean increase in the talocalcaneal height was 3.8 mm in the feet operated without grafting, whereas it was 8.1 mm in the feet for which grafting was performed. Improvement in talocalcaneal angle was significantly better in the feet operated with bone grafting. The feet with posttraumatic subtalar arthritis were more prone to Reflex Sympathetic Dystrophy. PMID- 26280870 TI - Acute acromioclavicular dislocation: a cheaper, easier and all-arthroscopic system. Is it effective in nowadays economical crisis? AB - The objective of this manuscript is to show an effective, easier and cheaper way to reduce acute acromioclavicular (AC) dislocation type III and V (Rockwood classification). Numerous procedures have been described for surgical management of acromioclavicular joint disruption. Newest devices involve an arthroscopic technique that allows nonrigid anatomic fixation of the acromioclavicular joint. Arthroscopically assisted treatment of acute AC joint dislocation is advantageous because it provides good clinical results and few complications. It also allows reviewing glenohumeral associated lesions. This surgical technique requires no specific implants to achieve a correct AC reduction. Actually, economical advantages are very important factors to decide the use of determinate surgical techniques. PMID- 26280871 TI - Proteomic study of pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome in rats. AB - Pyrrolizidine alkaloids (PAs) are a group of phytotoxins that can induce human liver injury, particularly hepatic sinusoidal obstruction syndrome (HSOS). To date, the molecular targets of PA-induced HSOS are largely unknown. In this study, retrorsine (RTS), a known hepatotoxic PA, was used as a representative PA for proteomic studies. Toxicological assessment demonstrated that 35 mg/kg RTS (designated as RTS-L) caused early lesions of HSOS at 24 h after dosing. A proteomic approach revealed 17 up-regulated and 31 down-regulated proteins in RTS L-treated rats. Subsequently, bioinformatic analysis suggested that two proteins, carbamoyl-phosphate synthase (CPS1) (p < 0.05) and ATP synthase subunit beta (ATP5B) (p < 0.01) were associated with RTS-L intoxication. Using immunohistochemical staining, we further verified the down-regulation of CPS1 and ATP5B in RTS-L-treated rats. These findings indicated that CPS1 and ATP5B were altered in the RTS-induced early lesions of HSOS in rats, and therefore, these two proteins and their involved pathways might play important roles in the initiation of HSOS. To the best of our knowledge, our study using a proteomic approach combined with conventional toxicological assessment is the first systems toxicology study on PA-induced HSOS. The results of this study provide novel findings on protein profiles in response to PA exposure, which can serve as a starting point to further investigate potential protein targets and their interactions with PAs to induce HSOS. PMID- 26280872 TI - An Obtuse Rhombohedral Superlattice Assembled by Pt Nanocubes. AB - We grew large single three-dimensional supercrystals from colloidal Pt nanocubes (NCs) suspended in hexane. A synchrotron-based two circle diffractometer was used to obtain an unprecedented level of detail from full sets of small/wide-angle X ray scattering (SAXS/WAXS) patterns. Automatic indexing and simulations of X-ray patterns enabled detailed reconstruction of NC translation and shape orientation within the supercrystals from atomic to mesometric levels. The supercrystal has an obtuse rhombohedral (Rh) superlattice with space group R3m and a trigonal cell angle of 106.2 degrees . Individual NCs orient themselves in a manner of atomic Pt[111] parallel to superlattice Rh[111]. We analyzed the superlattice structure in context of three spatial relationships of proximate NCs including face-to face, edge-to-edge, and corner-to-corner configurations. Detailed analysis of supercrystal structure reveals nearly direct corner-to-corner contacts and a tight interlocking NC structure. We employed the correlations between strain and lattice distortion and established the first structural correlating mechanism between five superlattice polymorphs to elucidate the superlattice transformations and associated developing pathways. Together, the experimental and modeling results provide comprehensive structural information toward controlling design and efficient materials-processing for large fabrication of nanobased functional materials with tailored structures and desired properties. PMID- 26280873 TI - Isolated Lingual Dyskinesia in Multiple Sclerosis. PMID- 26280874 TI - Testing Variations on Family-Style Feeding To Increase Whole Fruit and Vegetable Consumption among Preschoolers in Child Care. AB - BACKGROUND: Preschoolers do not consume whole fruit and vegetables (FVs) in recommended quantities. Two strategies to increase FV intake were tested. METHODS: One Head Start preschool participated. Two variations of family-style feeding were compared to usual practice: (1) Fruits, vegetables, and milk were served before the main meal (first course); and (2) fruits, vegetables, and milk were served before the main meal and meats and grains were removed from the table after the first serving (combination). A within-subject crossover design was used to test each condition for three meals. The amount of food served and consumed was weighed and converted to Child and Adult Care Feeding Program (CACFP) standard serving sizes for analysis. RESULTS: Eighty-five children ages 3-5 participated. The sample was 81% Hispanic with diverse racial backgrounds. Thirty percent of the children were overweight. FV consumption was at CACFP recommended levels at baseline and remained consistent across conditions. The average amount served for each meal component was at or above CACFP recommendations for all foods except milk, which was consistently served in small portions. Meat and grains servings were frequently 2-3 times larger than CACFP recommendations. Milk consumption was significantly higher in the Combined intervention for two meals. Children ate significantly less meat during the Combined intervention for one meal. CONCLUSIONS: The intervention led to significant increases in milk consumption, which was the only underconsumed meal component. These strategies should be tested with children who have lower baseline intake of FVs. PMID- 26280876 TI - INFLAMMATORY MARKERS ASSOCIATED WITH TRAUMA AND INFECTION IN RED-TAILED HAWKS (BUTEO JAMAICENSIS) IN THE USA. AB - Changes in inflammatory marker concentrations or activity can be used to monitor health and disease condition of domestic animals but have not been applied with the same frequency to wildlife. We measured concentrations or activity of six inflammatory markers (ceruloplasmin, haptoglobin, mannan-binding lectin-dependent complement [MBL/complement], unsaturated iron-binding capacity (UIBC) and total iron-binding capacity (TIBC), and plasma iron) in apparently healthy and sick or injured Red-tailed Hawks (Buteo jamaicensis). Haptoglobin and ceruloplasmin activities were consistently elevated in sick or injured hawks (2.1 and 2.5 times higher, respectively), and plasma iron concentrations decreased (0.46 times lower), relative to those of healthy birds. There were no differences between healthy and unhealthy hawks in TIBC and UIBC concentrations or MBL/complement activity. Therefore, haptoglobin, ceruloplasmin, and plasma iron would be useful inclusions in a panel of inflammatory markers for monitoring health in raptors. PMID- 26280875 TI - A combined clinical and biomarker approach to predict diuretic response in acute heart failure. AB - BACKGROUND: Poor diuretic response in acute heart failure is related to poor clinical outcome. The underlying mechanisms and pathophysiology behind diuretic resistance are incompletely understood. We evaluated a combined approach using clinical characteristics and biomarkers to predict diuretic response in acute heart failure (AHF). METHODS AND RESULTS: We investigated explanatory and predictive models for diuretic response--weight loss at day 4 per 40 mg of furosemide--in 974 patients with AHF included in the PROTECT trial. Biomarkers, addressing multiple pathophysiological pathways, were determined at baseline and after 24 h. An explanatory baseline biomarker model of a poor diuretic response included low potassium, chloride, hemoglobin, myeloperoxidase, and high blood urea nitrogen, albumin, triglycerides, ST2 and neutrophil gelatinase-associated lipocalin (r(2) = 0.086). Diuretic response after 24 h (early diuretic response) was a strong predictor of diuretic response (beta = 0.467, P < 0.001; r(2) = 0.523). Addition of diuretic response after 24 h to biomarkers and clinical characteristics significantly improved the predictive model (r(2) = 0.586, P < 0.001). CONCLUSIONS: Biomarkers indicate that diuretic unresponsiveness is associated with an atherosclerotic profile with abnormal renal function and electrolytes. However, predicting diuretic response is difficult and biomarkers have limited additive value. Patients at risk of poor diuretic response can be identified by measuring early diuretic response after 24 h. PMID- 26280878 TI - THE PARADOX OF EUTHANIZING KOALAS (PHASCOLARCTOS CINEREUS) TO SAVE POPULATIONS FROM ELIMINATION. AB - Koala (Phascolarctos cinereus) populations in the wild are in sharp decline in Australia due to deforestation, road accidents, dog attacks, and disease from infection with sexually transmitted Chlamydia spp. Severely diseased koalas that are captured are euthanized for humane reasons because antibiotics are not effective. Paradoxically, we propose that euthanizing more koalas could help to increase koala population numbers. We investigated the potential impact of systematically euthanizing diseased koalas. Using data from a well-studied koala population, and an individual-based computer simulation model, we predict that such a program would result in a larger population of koalas after 7 yr than would exist without the program. If terminally diseased and sterile koalas are euthanized and other infected captured koalas are given antibiotics, chlamydial infection could be eliminated and population growth observed after 4 yr. The practical implementation of such a program would be facilitated with further development of tools to diagnose infection and internal disease in the field. PMID- 26280877 TI - Identification of Novel Gammaherpesviruses in Ocelots (Leopardus pardalis) and Bobcats (Lynx rufus) in Panama and Colorado, USA. AB - Gammaherpesviruses (GHVs) have been identified in many species and are often associated with disease. Recently, we characterized three novel felid GHVs in domestic cats (Felis catus), bobcats (Lynx rufus), and pumas (Puma concolor). We investigated whether free-ranging ocelots (Leopardus pardalis) and bobcats are infected with additional GHVs. We screened DNA samples from ocelots on Barro Colorado Island, Panama, and bobcats in western Colorado, US, by using a degenerate nested PCR that targets the GHV glycoprotein B gene. We identified a novel GHV glycoprotein B sequence in two ocelots and a second novel sequence in a bobcat, which is distinct from the previously characterized bobcat GHV (Lynx rufus GHV 1). Utilizing additional degenerate and virus-specific PCRs, we extended these sequences to include 3.4 kilobases of the GHV glycoprotein B and DNA polymerase genes. These sequences identify the first GHV detected in ocelots and the second GHV in bobcats. These viruses were provisionally named L. pardalis GHV 1 and Lynx rufus GHV 2, respectively. The viruses are most closely related to recently identified GHVs of the Percavirus genus found in domestic cats (F. catus GHV 1) and bobcats (L. rufus GHV 1), suggesting that a cluster of felid GHVs exists within the Percavirus genus. PMID- 26280879 TI - DENTAL ABNORMALITIES OF EIGHT WILD QINLING GIANT PANDAS (AILUROPODA MELANOLEUCA QINLINGENSIS), SHAANXI PROVINCE, CHINA. AB - Eight adult (six male and two female) wild Qinling giant pandas (Ailuropoda melanoleuca qinlingensis) from China National Foping Nature Reserve were tracked, and their dental data collected and recorded from October 2010 to April 2014. Each panda had dental abnormalities of varying severity. Dental wear and fracture were the most common conditions. Absent teeth were common, with premolars missing most often. Mild caries were present in five molar teeth between two animals. Different degrees of dental plaque and calculus occurred in all animals but without severe periodontal disease. Two animals with severe dental abnormalities died due to intestinal problems. Large segments of bamboo were found in their intestinal tracts, and intestinal perforation and ulcers were evident, indicating dental abnormalities can be an important factor in the health of wild giant pandas and may lead to death. Further research with larger sample sizes of wild and captive giant pandas will be required to substantiate the relationship between dental abnormalities and mortality in giant pandas. PMID- 26280880 TI - Hematologic and Serum Biochemical Reference Intervals for the Bilby (Macrotis lagotis). AB - Hematologic and serum biochemistry blood reference intervals were established for the endangered marsupial, the bilby (Macrotis lagotis). Blood samples were collected from 135 bilbies that were housed in a captive breeding colony or were free ranging in a 10-ha exclosure. Statistical analyses were undertaken, and significant differences in parameters were found depending on age, sex, and captive or free-ranging status of animals. These reference intervals will assist ongoing health and conservation management of this endangered marsupial species. PMID- 26280881 TI - The Parasite Fauna of the Gyrfalcon (Falco rusticolus) in Iceland. AB - We examined 46 Gyrfalcon (Falco rusticolus) carcasses from Iceland for parasites, including 29 first-year birds and 17 second-year birds and older. Endoparasites observed were the trematodes Cryptocotyle lingua (prevalence 8%), Cryptocotyle concavum (4%), and Strigea sp. (8%); the cestode Mesocestoides sp. (27%); and the nematodes Eucoleus contortus (76%) and Serratospiculum guttatum (7%). Ectoparasites included the astigmatan mite Dubininia accipitrina (47%), a mesostigmatan rhynonyssid mite (4%), the tick Ixodes caledonicus (20%), the mallophagans Degeeriella rufa (90%) and Nosopon lucidum (7%), the flea Ceratophyllus vagabundus (7%), and the louse fly Ornithomya chloropus (7%). Cryptocotyle lingua, C. concavum, S. guttatum, D. accipitrina, I. caledonicus, and N. lucidum are new host records. Of the five most common parasites (prevalence >= 20%) only Mesocestoides sp. showed a significant age relationship, being more prevalent in adult falcons (P = 0.021). Eucoleus contortus was also more prevalent in adults with marginal statistical significance (P = 0.058). Frounce, caused by E. contortus (possibly also by Trichomonas gallinae, which was not searched for in the survey) was highly prevalent (43%), but did not show a relationship with host age (P = 0.210). Birds with frounce were in poorer body condition than healthy birds (P = 0.015). PMID- 26280883 TI - Multiphase Postmortem Computed Tomography Angiography in Pediatrics: A Case Report. AB - Postmortem imaging techniques, especially postmortem computed tomography, have become integral tools in forensic investigations. Multiphase postmortem computed tomography angiography (MPMCTA) visualizes the vascular system in detail and makes it possible to evaluate the perfusion of even the smallest vessels. Although the technique has been well described for adults, no pediatric cases have been reported and no pediatric protocol has been established for this type of investigation. We present the case a 7-year-old child for which we used a previously described MPMCTA protocol and adapted values of perfusion, with the same technical equipment as for adult cases. Our main objective was to propose a perfusion protocol adapted for the investigation of infants and children. Moreover, we discuss both the difficulties that we encountered and possible ways to further improve the investigation of pediatric cases by MPMCTA. PMID- 26280882 TI - Symptomatic sensorineural hearing loss in patients with ulcerative colitis. AB - BACKGROUND: Sensorineural hearing loss has been reported as an extraintestinal manifestation of inflammatory bowel disease, especially in adult patients with ulcerative colitis. However, to date only a few series have been reported in the literature, and none from Italy. The aim of the present investigation was to assess the prevalence of symptomatic sensorineural hearing loss in Italian patients with ulcerative colitis. METHODS: We retrospectively assessed the charts of all patients with ulcerative colitis who underwent otolaryngologic investigation in a 10-year period. RESULTS: Complete charts of 57 patients were available for the observation period. Reasons for head and neck investigation were transient, mild hearing loss and sporadic vertigo. Clinical and instrumental head and neck examination was unremarkable in all but one woman who complained of mild hearing loss without vertigo or tinnitus, in whom sensorineural hearing loss was diagnosed. CONCLUSIONS: In our series, sensorineural hearing loss was found in less than 2 % of adult patients with ulcerative colitis evaluated in a department of otolaryngology. Systematic evaluation for this extraintestinal manifestation should not be carried out unless hearing loss is present. PMID- 26280884 TI - Nontraumatic Retroperitoneal Hematoma After Warfarin Administration: Fatal Case Report and Review of the Literature. AB - Spontaneous retroperitoneal hematoma after warfarin therapy is an extremely rare event. Here, we report a 25-year-old man who was brought in to the emergency service with confusion. On arrival, the patient had hypotension, tachycardia, tachypnea, low-grade fever, and Glasgow Coma Scale score of 12. Abdominal examination revealed distention and mild tenderness in the right upper quadrant of the abdomen. The patient had a history of aortic valve replacement surgery and was on warfarin treatment at an international normalized ratio of 2.4. Our patient progressed to cardiorespiratory arrest. The resuscitation was initiated promptly. Despite all resuscitation measures, including transfusion and administration of high doses of catecholamine, the patient died of hypovolemic shock 3 hours after admission. At autopsy, the external surface of the abdominal great vessels (descending aorta and mesenteric vessels) showed scattered petechial hemorrhages without any visible site of perforation. After comprehensive exploration of the abdomen, no evidence of traumatic event was identified and the cause of internal blood loss was noted as warfarin adverse effect. PMID- 26280885 TI - Use of renal risk drugs in patients with renal impairment. AB - BACKGROUND: Renal impairment often goes unrecognised until the most advanced stages. Patients with renal impairment use a variety of drugs and the pharmacokinetics and drug effects are prone to change. OBJECTIVE: Describe drug related problems in a population of patients with renal impairment, investigate possible risk factors, and investigate whether the clinical pharmacist can propose relevant measures to solve the problems. SETTING: The internal medicine department at Innlandet Hospital Trust Gjovik, Norway. METHOD: A prospective study enrolling patients (>=18 years) with moderate and severe renal impairment, i.e. with glomerular filtration rate of 30-59 and 15-29 ml/min/1.73 m(2), respectively, and using at least one drug. The clinical pharmacist reviewed the patients' drug regimen with focus on drug related problems, related to renal function. Problems identified were discussed with the multidisciplinary team, or directly with the physician. MAIN OUTCOME MEASURE: The number of drug related problems. RESULTS: The results are based on data from 79 patients, 21 with severe and 58 with moderate renal impairment. Most patients, 92.4 %, used 5 or more drugs; in average 10.2 (range 2-27). In total, 88 drug related problems were identified in 49 patients, i.e. in 62 %. The most frequently occurring problems were incorrect dose (45.5 %) and inappropriate drug (41.0 %). There was a significant correlation between both the degree of renal impairment and the number of drugs, and the number of drug related problems. The acceptance rate of the clinical pharmacist's interventions was 95.7 %. The drugs most frequently associated with drug related problems were metformin, benzylpenicillin and furosemide. CONCLUSION: Drug related problems often occur in patients with renal impairment. Incorrect drug dose and inappropriate drug choice according to the patients' renal function were the most common problems. Patients with the most complex drug treatment, i.e. with increasing degree of renal impairment and increasing number of drugs, are at greater risk of drug related problems. The high acceptance rate for the pharmacist's interventions supports the inclusion of a clinical pharmacist in the multidisciplinary treatment team to increase awareness and optimisation of the drug treatment in this patient group. PMID- 26280886 TI - Monoterpenoid Indole Alkaloids from Inadequately Dried Leaves of Alstonia scholaris. AB - Six new indole alkaloids, named alstoniascholarines L-Q (1-6), together with nineteen known analogues were isolated from the inadequately dried leaves of Alstonia scholaris. Their structures were elucidated on the basis of extensive analysis of spectroscopic data and by comparison of their physical and spectroscopic data with the literature values. In addition, the new alkaloids were tested for their cytotoxic and neurite outgrowth-promoting activities. PMID- 26280887 TI - Immune Regulation by Dead Cell Clearance. AB - When cell death occurs in vivo, cell corpses are not left untreated, but are recognized and engulfed by phagocytes, such as macrophages and dendritic cells. In the past, cell death had been considered the final process of a cell's life, and cell corpses had been viewed as debris that is simply to be cleared by phagocytes. Recently, however, it has become clearer that various biological responses are induced with dead cells as the starting point. Most of these biological responses followed by cell death are thought to be mediated by macrophages and dendritic cells. In this review, we present the overview of molecular mechanisms and biological significance of dead cell clearance. PMID- 26280888 TI - Hormonal and intrauterine methods for contraception for women aged 25 years and younger. AB - BACKGROUND: Women between the ages of 15 and 24 years have high rates of unintended pregnancy; over half of women in this age group want to avoid pregnancy. However, women under age 25 years have higher typical contraceptive failure rates within the first 12 months of use than older women. High discontinuation rates may also be a problem in this population. Concern that adolescents and young women will not find hormonal or intrauterine contraceptives acceptable or effective might deter healthcare providers from recommending these contraceptive methods. OBJECTIVES: To compare the contraceptive failure (pregnancy) rates and to examine the continuation rates for hormonal and intrauterine contraception among young women aged 25 years and younger. SEARCH METHODS: We searched until 4 August 2015 for randomized controlled trials (RCTs) that compared hormonal or intrauterine methods of contraception in women aged 25 years and younger. Computerized databases included the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, POPLINE, CINAHL, and LILACS. We also searched for current trials via ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: We considered RCTs in any language that reported the contraceptive failure rates for hormonal or intrauterine contraceptive methods, when compared with another contraceptive method, for women aged 25 years and younger. The other contraceptive method could have been another intrauterine contraceptive, another hormonal contraceptive or different dose of the same method, or a non-hormonal contraceptive. Treatment duration must have been at least three months. Eligible trials had to include the primary outcome of contraceptive failure rate (pregnancy). The secondary outcome was contraceptive continuation rate. DATA COLLECTION AND ANALYSIS: One author conducted the primary data extraction and entered the information into Review Manager. Another author performed an independent data extraction and verified the initial entry. For dichotomous outcomes, we computed the Mantel-Haenszel odds ratio (OR) with 95% confidence interval (CI). Because of disparate interventions and outcome measures, we did not conduct meta-analysis. MAIN RESULTS: Five trials met the inclusion criteria. The studies included a total of 1503 women, with a mean of 301 participants. The trials compared the following contraceptives: combined oral contraceptive (COC) versus transdermal contraceptive patch, vaginal contraceptive ring, or levonorgestrel intrauterine system 20 ug/day (LNG-IUS 20); LNG-IUS 12 ug/day (LNG-IUS 12) versus LNG-IUS 16 ug/day (LNG-IUS 16); and LNG-IUS 20 versus the copper T380A intrauterine device (IUD). In the trials comparing two different types of methods, the study arms did not differ significantly for contraceptive efficacy or continuation. The sample sizes were small for two of those studies. The only significant outcome was that a COC group had a higher proportion of women who discontinued for 'other personal reasons' compared with the group assigned to the LNG-IUS 20 (OR 0.27, 95% CI 0.09 to 0.85), which may have little clinic relevance. The trial comparing LNG-IUS 12 versus LNG-IUS 16 showed similar efficacy over one and three years. In three trials that examined different LNG-IUS, continuation was at least 75% at 6 to 36 months. AUTHORS' CONCLUSIONS: We considered the overall quality of evidence to be moderate to low. Limitations were due to trial design or limited reporting. Different doses in the LNG-IUS did not appear to influence efficacy over three years. In another study, continuation of the LNG-IUS appeared at least as high as that for the COC. The current evidence was insufficient to compare efficacy and continuation rates for hormonal and intrauterine contraceptive methods in women aged 25 years and younger. PMID- 26280889 TI - High resolution FDG-microPET of carotid atherosclerosis: plaque components underlying enhanced FDG uptake. AB - This study sought to discover which atherosclerotic plaque components co-localize with enhanced [(18)F]-fluorodeoxyglucose (FDG) uptake in carotid positron emission tomography (PET) images. Although in vivo PET currently lacks the resolution, high-resolution ex vivo FDG-microPET with histology validation of excised carotid plaque might accomplish this goal. Thirteen patients were injected with FDG before carotid endarterectomy. After excision, the plaque specimens were scanned by microPET and magnetic resonance imaging, and then serially sectioned for histological analysis. Two analyses were performed using generalized linear mixed models: (1) a PET-driven analysis which sampled high and low FDG uptake areas from PET images to identify their components in matched histology specimens; and (2) a histology-driven analysis where specific plaque components were selected and matched to corresponding PET images. In the PET driven analysis, regions of high FDG uptake were more likely to contain inflammatory cells (p < 0.001) and neovasculature (p = 0.008) than regions of low FDG uptake. In the histology-driven analysis, regions with inflammatory cells (p = 0.001) and regions with loose extracellular matrix (p = 0.001) were associated with enhanced FDG uptake. Furthermore, areas of complex inflammatory cell infiltrate (co-localized macrophages, lymphocytes and foam cells) had the highest FDG uptake among inflammatory subgroups (p < 0.001). In conclusion, in carotid plaque, regions of inflammatory cell infiltrate, particularly complex one, co localized with enhanced FDG uptake in high-resolution FDG-microPET images. Loose extracellular matrix and areas containing neovasculature also produced FDG signal. This study points to the potential ability of FDG-PET to detect the cellular components of the vulnerable plaque. PMID- 26280890 TI - Plaque assessment by coronary CT. AB - Coronary CT angiography (CTA) has emerged as a highly reliable and non-invasive modality for the exclusion of coronary artery disease. Recent technological advancements in coronary CTA imaging allow for robust qualitative and quantitative assessment of atherosclerotic plaques. Furthermore, CTA is a promising modality for functional evaluation of coronary lesions. Individual plaque features, the extent and severity of atherosclerotic plaque burden were proposed to improve cardiovascular risk stratification. It has been suggested that total atherosclerotic plaque burden is a stronger predictor of coronary events than total ischemia burden. The quest to noninvasively detect individual vulnerable plaques still remains. In the current review we sought to summarize state-of-the-art coronary artery plaque assessment by CTA. PMID- 26280892 TI - Pregnancy Outcome in Patients with Common Variable Immunodeficiency. AB - PURPOSE: The aim of our retrospective study was to clarify fertility, pregnancy complications and outcomes in common variable immunodeficiency (CVID) females. METHODS: Retrospective data were obtained from three Czech referral centres. The data were compared with data obtained from the Czech National Registry of Reproduction Health. RESULTS: Our cohort of patients comprised 54 women with 115 pregnancies; 88 pregnancies in 50 females were finished with live births (77 %). In only 8 women (15%) was the diagnosis of CVID established before the first pregnancy. Replacement immunoglobulin therapy was performed in 10 patients without any moderate or severe adverse effects. Compared with the Czech population, the CVID patients suffered significantly more frequently from the threat of preterm labour (p < 0.0001), vaginal bleeding (p = 0.0001), eclampsia/preeclampsia (p = 0.009) and a higher number of stillbirths (p < 0.0001). Furthermore, the frequency of babies with low birth weight (less than 2500 g) born to the CVID patients was increased compared with the normal population (p < 0.0001). Serum IgG, IgA and IgM determination was done in 57 children of 50 mothers showing 13 cases of IgA deficiency (23%). There was no significant difference among the non-symptomatic, symptomatic untreated and symptomatic treated females in any of the determined gynaecological complications. The number of unsuccessful pregnancies was higher in the symptomatic untreated women. CONCLUSIONS: Fertility in CVID patients is not decreased, and their pregnancies could be considered more risky compared with those of the general population. PMID- 26280893 TI - Effects of preoperative and intraoperative glucose administration on glucose use and fat catabolism during laparotomy under sevoflurane anesthesia in fasted rats. AB - Preoperative fasting as well as surgical stress significantly modifies metabolisms. Recent studies reported the possible advantageous effects of glucose administration on perioperative metabolisms; however, the underlying mechanisms have not been fully elucidated. Rats were allocated to three groups. During the fasting period, groups A and B were administered water, but group C was administered glucose. During laparotomy and the insulin tolerance test (ITT) under sevoflurane anesthesia, group A was administered saline, but groups B and C were administered glucose. During laparotomy, group C showed higher glucose levels and lower beta-hydroxybutyrate (beta-OHB) levels than group A, and group B showed more decreases in beta-OHB levels than group A without differences in changes in glucose levels. Insulin levels and insulin sensitivity during laparotomy were similar among the three groups. No significant difference in insulin sensitivity was also confirmed in ITT. In conclusion, perioperative glucose administration suppresses lipolysis without affecting insulin secretion and sensitivity. PMID- 26280891 TI - The Ying and Yang of STAT3 in Human Disease. AB - The transcription factor signal transducer and activator of transcription 3 (STAT3) is a critical regulator of multiple, diverse cellular processes. Heterozgyous, germline, loss-of-function mutations in STAT3 lead to the primary immune deficiency Hyper-IgE syndrome. Heterozygous, somatic, gain-of-function mutations in STAT3 have been reported in malignancy. Recently, germline, heterozygous mutations in STAT3 that confer a gain-of-function have been discovered and result in early-onset, multi-organ autoimmunity. This review summarizes what is known about the role of STAT3 in human disease. PMID- 26280894 TI - Expression of SIRT1 and apoptosis-related proteins is predictive for lymph node metastasis and disease-free survival in luminal A breast cancer. AB - Luminal A breast cancer can present with early, unexpected lymph node metastasis, and sentinel lymph node biopsy has been reported false negative in some cases. We aimed to construct a biomarker-based model that predicts lymph node metastasis in luminal A breast cancer, using expression of silent mating type information regulation 2 homolog 1 (SIRT1) and apoptosis-related factors, which are known to be closely related. We selected tissue samples of 278 cases of luminal A invasive ductal carcinoma, constructed tissue microarrays, and performed immunohistochemical staining for SIRT1 and four apoptosis-related proteins. In constructing the best predictive model for lymph node metastasis, six clinicopathological parameters and five molecular markers were considered. Independent factors predictive of lymph node metastasis were pT stage (OR 1.829, p = 0.027), lymphovascular invasion (OR 4.128, p < 0.001), and decreased expression of caspase-3 (OR 0.535, p = 0.034) and of SIRT1 (OR 0.526, p = 0.053). A combination nuclear grade, lymphovascular invasion, increased B-cell lymphoma 2 (Bcl-2) expression, and reduced expression of caspase-3 and of SIRT1 yielded the strongest predictive performance for lymph node metastasis with an area under the curve (AUC) of 0.696. This combination was also predictive of shortened disease free survival (73.1 vs. 67.7 months, p = 0.003). Our data support a role of SIRT1 protein as tumor suppressor in luminal A breast cancer, in association with apoptosis-related proteins. Our model based upon a combination of these biomarkers is expected to increase accuracy of prediction of lymph node metastasis in luminal A breast cancer. This might serve as a valuable tool in determining the optimal surgical strategy in breast cancer patients. PMID- 26280896 TI - Symptom Burden Among Patients Who Were Hospitalized for Heart Failure. PMID- 26280895 TI - Spatio-temporal Use of Oral Rabies Vaccines in Fox Rabies Elimination Programmes in Europe. AB - In Europe, the elimination of wildlife rabies using oral rabies vaccination [ORV] of foxes for more than 30 years has been a success story. Since a comprehensive review on the scope of the different oral rabies vaccine baits distributed across Europe has not been available yet, we evaluated the use of different vaccine baits over the entire period of ORV [1978-2014]. Our findings provide valuable insights into the complexity of ORV programs in terms of vaccine related issues. More than 10 oral vaccines against rabies were used over the past four decades. Depending on many factors, the extent to which oral rabies virus vaccines were used varied considerably resulting in huge differences in the number of vaccine doses disseminated in ORV campaigns as well as in large spatial and temporal overlaps. Although vaccine virus strains derived from the SAD rabies virus isolate were the most widely used, the success of ORV campaigns in Europe cannot be assigned to a single oral rabies virus vaccine alone. Rather, the successful elimination of fox rabies is the result of an interaction of different key components of ORV campaigns, i.e. vaccine strain, vaccine bait and strategy of distribution. PMID- 26280897 TI - Disability Pensions due to Skin Diseases: A Cohort Study in Swedish Construction Workers. AB - Disability pensions due to skin diseases in Swedish male construction workers were studied by linking data from pension registers and an occupational health service. Incidence rates of disability pensions for cement workers, painters and plumbers were compared with 2 control groups. A total of 623 disability pensions were granted during 4 decades of follow-up. The main diagnoses were eczema (36%) and psoriasis (49%). Pensions were mostly granted in the age range 55-64 years. Among painters, cement workers and plumbers the incidence rates for disability pensions were 33.3, 24.5 and 20.4 cases/100,000 person-years, respectively, compared with 13.7 and 9.2 cases/100,000 person-years in control groups. Relative risks were highest for eczema, and were notable for psoriasis. Attributable fractions for eczema were 90% in cement workers and painters and 75% in plumbers compared with control groups. Attributable fractions for psoriasis in the occupational groups studied were in the range 54-67%. In conclusion, eczema and psoriasis have a high impact on loss of work ability, as reflected by disability pensions. PMID- 26280898 TI - Synthesis and Biological Evaluation of Fluorinated 3-Phenylcoumarin-7-O-Sulfamate Derivatives as Steroid Sulfatase Inhibitors. AB - In the present work, we report the initial results of our study on a series of 3 phenylcoumarin sulfamate-based compounds containing C-F bonds as novel inhibitors of steroid sulfatase. The new compounds are potent steroid sulfatase inhibitors, possessing more than 10 times higher inhibitory potency than coumarin-7-O sulfamate. In the course of our investigation, compounds 2b and 2c demonstrated the highest inhibitory effect on the enzymatic steroid sulfatase assay; both had IC50 values of 0.27 MUm (the IC50 value of coumarin-7-O-sulfamate is 3.5 MUm, used as a reference). PMID- 26280899 TI - Complement Modulation of Anti-Aging Factor Klotho in Ischemia/Reperfusion Injury and Delayed Graft Function. AB - Klotho is an anti-aging factor mainly produced by renal tubular epithelial cells (TEC) with pleiotropic functions. Klotho is down-regulated in acute kidney injury in native kidney; however, the modulation of Klotho in kidney transplantation has not been investigated. In a swine model of ischemia/reperfusion injury (IRI), we observed a remarkable reduction of renal Klotho by 24 h from IRI. Complement inhibition by C1-inhibitor preserved Klotho expression in vivo by abrogating nuclear factor kappa B (NF-kB) signaling. In accordance, complement anaphylotoxin C5a led to a significant down-regulation of Klotho in TEC in vitro that was NF-kB mediated. Analysis of Klotho in kidneys from cadaveric donors demonstrated a significant expression of Klotho in pre-implantation biopsies; however, patients affected by delayed graft function (DGF) showed a profound down-regulation of Klotho compared with patients with early graft function. Quantification of serum Klotho after 2 years from transplantation demonstrated significant lower levels in DGF patients. Our data demonstrated that complement might be pivotal in the down-regulation of Klotho in IRI leading to a permanent deficiency after years from transplantation. Considering the anti-senescence and anti-fibrotic effects of Klotho at renal levels, we hypothesize that this acquired deficiency of Klotho might contribute to DGF-associated chronic allograft dysfunction. PMID- 26280902 TI - Effects of Se on the Diversity of SelT Synthesis and Distribution in Different Smooth Muscle Tissues in Rats. AB - Selenium (Se) is a nutritionally essential trace element associated with health and disease, including many muscle diseases. Selenoprotein T (SelT) has been identified as a member of the redoxin protein family that includes selenocysteine, localizing to the endoplasmic reticulum. The synthesis of selenoprotein is influenced by Se. However, there is currently no data concerning the pattern of SelT expression in smooth muscle tissues. To investigate the effects of dietary Se on the expression of SelT, 90 rats were randomly allocated into three groups: LG, NG, and HG. The LG group was fed a basal diet deficient in Se (containing 0.023 mg/kg Se); the NG and HG groups were fed Se-supplemented diets containing either 0.3 or 1.5 mg/kg Se, respectively, for 90 days. The smooth muscle of the esophagus, trachea, stomach, intestine, and blood vessels was collected when the rats were 90 days old. The Se content in the blood and tissues was examined. The messenger RNA (mRNA) of selenocysteine-tRNA([Ser]Sec) synthase (SecS), selenophosphate synthetase 1 (SPS1), selenophosphate synthetase 2 (SPS2), and SelT were examined using qPCR, and SelT protein was detected by Western blotting. The results indicated that Se had an effect on the mRNA levels of SecS, with little effect on those of SPS1 in smooth muscle tissues. SelT was expressed in the smooth muscle tissues of blood vessels, esophagus, bronchus, stomach, and intestine, and the transcription of the SelT was very sensitive to dietary Se. Thus, SelT may play a major role in the mechanisms underlying the biological activity of Se in smooth muscle tissues. PMID- 26280901 TI - Absence of canonical marks of active chromatin in developmentally regulated genes. AB - The interplay of active and repressive histone modifications is assumed to have a key role in the regulation of gene expression. In contrast to this generally accepted view, we show that the transcription of genes temporally regulated during fly and worm development occurs in the absence of canonically active histone modifications. Conversely, strong chromatin marking is related to transcriptional and post-transcriptional stability, an association that we also observe in mammals. Our results support a model in which chromatin marking is associated with the stable production of RNA, whereas unmarked chromatin would permit rapid gene activation and deactivation during development. In the latter case, regulation by transcription factors would have a comparatively more important regulatory role than chromatin marks. PMID- 26280900 TI - Germline duplication of ATG2B and GSKIP predisposes to familial myeloid malignancies. AB - No major predisposition gene for familial myeloproliferative neoplasms (MPN) has been identified. Here we demonstrate that the autosomal dominant transmission of a 700-kb duplication in four genetically related families predisposes to myeloid malignancies, including MPN, frequently progressing to leukemia. Using induced pluripotent stem cells and primary cells, we demonstrate that overexpression of ATG2B and GSKIP enhances hematopoietic progenitor differentiation, including of megakaryocytes, by increasing progenitor sensitivity to thrombopoietin (TPO). ATG2B and GSKIP cooperate with acquired JAK2, MPL and CALR mutations during MPN development. Thus, the germline duplication may change the fitness of cells harboring signaling pathway mutations and increases the probability of disease development. PMID- 26280903 TI - cAMP/PKA Signaling Pathway Induces Apoptosis by Inhibited NF-kappaB in Aluminum Chloride-Treated Lymphocytes In Vitro. AB - To explore the apoptosis mechanism in lymphocytes of rats induced by aluminum chloride (AlCl3) by activating cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway, the splenic lymphocytes of rats were cultured and exposed to different concentrations of AlCl3 for 24 h. The final concentrations of AlCl3 (AlCl3 . 6H2O) in supernatant were 0 (control group, CG), 0.3 mmol/L (low-dose group, LG), 0.6 mmol/L (mid-dose group, MG), and 1.2 mmol/L (high-dose group, HG), respectively. Lymphocytes Apoptosis rate, intracellular cAMP content, PKA, survivin, B cell lymphoma/leukemia-2 (Bcl-2) and Bcl-2 associated X protein (Bax) mRNA expressions, and the mRNA and protein expressions of nuclear factor-kappa-gene binding (NF-kappaB, p65) were detected, respectively. The results showed that apoptosis index of lymphocytes, cAMP content in intracellular and PKA mRNA expression were significantly upregulated, whereas NF-kappaB and survivin mRNA expressions, nuclear NF-kappaB (p65) protein expression, and the ratio of Bcl-2 and Bax mRNA expression were downregulated in the AlCl3-treated groups compared with those in CG. The results indicated that the activated cAMP/PKA signaling pathway induces apoptosis by inhibited NF-kappaB in AlCl3-treated lymphocytes in vitro. PMID- 26280904 TI - Comparison of three retreatment techniques with ultrasonic activation in flattened canals using micro-computed tomography and scanning electron microscopy. AB - AIM: To use micro-CT to quantitatively evaluate the amount of residual filling material after using several techniques to remove root fillings with and without ultrasonic activation and to analyse the cleanliness of the root canal walls and dentine tubules with scanning electron microscopy (SEM). METHODOLOGY: The root canals of one hundred and eight human mandibular incisors were selected and instrumented with rotary files using the BioRace system up to file size 40, .04 taper. After instrumentation, the teeth were filled using a hybrid technique with gutta-percha and sealer then divided into three groups according to the method used for removing the root filling: G1-Reciproc (using only instrument R50), G2 ProTaper Universal retreatment system and G3-Manual (hand files and Gates-Glidden burs). All groups were divided into two subgroups depending on whether ultrasonic agitation was used with the irrigants. Micro-CT scans were taken before and after removal of the filling material to detect residual material in the canal. After micro-CT analysis, the roots were cut in half, imaged by SEM and scored based on the amount of surface covered by root filling remnants. The data were analysed statistically using a significance level of 5%. RESULTS: All groups had retained material in the root canals after instrumentation. The Reciproc method was associated with less retained material than the ProTaper and Manual methods. Ultrasonic activation significantly reduced the amount of residual root filling in all groups (P < 0.05). CONCLUSION: None of the instrumentation methods were able to completely remove root filling material. Ultrasonic activation improved the removal of root filling material in all groups. PMID- 26280905 TI - Mechanistic Study on the Formation of Cl-/Br-/I-Trihalomethanes during Chlorination/Chloramination Combined with a Theoretical Cytotoxicity Evaluation. AB - Chlorination followed by chloramination can be used to mitigate the formation of potentially toxic iodinated disinfection byproducts (I-DBPs) while controlling the formation of regulated chloro-bromo-DBPs (Cl-/Br-DBPs). Water samples containing dissolved organic matter (DOM) isolates were subjected to 3 disinfection scenarios: NH2Cl, prechlorination followed by ammonia addition, and HOCl alone. A theoretical cytotoxicity evaluation was carried out based on the trihalomethanes (THMs) formed. This study demonstrates that the presence of bromide not only enhances the yield and rate of iodate formation, it also increases the formation of brominated I-THM precursors. A shift in the speciation from CHCl2I to the more toxic CHBr2I, as well as increased iodine incorporation in THMs, was observed in the presence of bromide. For low bromide concentrations, a decrease in I-THM formation and theoretical cytotoxicity was achieved only for high prechlorination times, while for high bromide concentrations, a short prechlorination time enabled the full conversion of iodide to iodate. For low DOM concentrations or DOM with low reactivity, Br-/I-THMs were preferentially formed for short prechlorination times, inducing high cytotoxicity. However, for high chlorine exposures, the cytotoxicity induced by the formation of regulated THMs might outweigh the benefit of I-THM mitigation. For high DOM concentrations or DOM with higher reactivity, mixed I-THMs were formed together with high concentrations of regulated THMs. In this case, based on the cytotoxicity of the THMs formed, the use of NH2Cl is recommended. PMID- 26280906 TI - Rugby Football: Fascinating Sport, Exceptional History and Developments, Immense Potential for Research. PMID- 26280907 TI - Kinetics of Multielectron Transfers and Redox-Induced Structural Changes in N Aryl-Expanded Pyridiniums: Establishing Their Unusual, Versatile Electrophoric Activity. AB - A combined electrochemical and theoretical study of a series of pyridinium-based electrophores, consisting of reference N-alkyl-2,4,6-triarylpyridiniums (1-3) and N-aryl-expanded pyridiniums (EPs), i.e. N-aryl-2,4,6-triarylpyridiniums (4-10), is presented with the aim of elucidating multifaceted mechanisms underpinning the complex electrophoric activity of fluxional EP systems. Series 1-10 constitutes a library of model electrophores showing an incremental variation of their composition, charge, and steric hindrance. By kinetic mapping of the first two heterogeneous electron transfers (ETs) of 1-10 and computational mapping, at the density functional theory level, of their electronic and geometrical features in various redox states, it is established that, depending on whether EPs are made of one (4, 5) or two "head-to-tail"-connected pyridinium rings (6-10), the nature of the redox-triggered distortions (when allowed) is different, namely, N pyramidalization due to hybridization change in the former case versus saddle shaped distortion originating from conflicting intramolecular interactions in the latter case (8-10). When skeletal relaxations are sterically hampered, zwitterionic states and electron delocalization with quinoidal features are promoted as alternative relaxation modes. It follows that "potential compression" is changed to "potential expansion" (i.e., a further separation of redox potentials) in single-pyridinium EPs (4, 5), whereas "potential inversion" (i.e., single-step two-electron transfer; 8-10) is changed to stepwise ETs of the Weitz type for two-pyridinium EPs (6, 7). Overall, kinetic rate constants not only consistently indicate the most prominent mechanistic aspects of the reduction pathways of EPs, but they are also instrumental in establishing EPs as a unique class of electrophores. PMID- 26280908 TI - Physiologic significance of coronary collaterals in chronic total occlusions. AB - Chronic total occlusions (CTOs) are commonly found in patients with coronary artery disease, and a system of collateral connections are found in almost all of these patients. These collateral vessels serve to prevent myocardial necrosis but are not sufficient to prevent myocardial ischemia during exercise. Unfortunately, the presence of well-developed collaterals has been used as argument against CTO revascularization. Many continue to falsely believe that these patients are "protected" by collaterals and, therefore, CTO recanalization is not indicated. Our knowledge of the physiologic significance of coronary collaterals has increased significantly over the past several years. Studies utilizing coronary pressure and flow velocity have answered a number of basic physiologic questions. We therefore sought to review the evidence for coronary collateral flow and their clinical significance in patients with CTOs. PMID- 26280909 TI - Knowledge, attitudes and beliefs of parents regarding fever in children: a Danish interview study. AB - AIM: Fever and febrile illness are some of the most common conditions managed by parents. The aim of this study was to examine the knowledge, attitudes and beliefs of parents around fever in children under five years of age. METHODS: Between July and August 2014, a convenience sample of parents was invited to participate in this study in Copenhagen, Denmark. Results were analysed thematically using a constant comparison method. RESULTS: Twenty-one parents participated in the study. Five themes emerged from the data: parental concern, help-seeking behaviour, parental knowledge, parent fever management practices and initiatives. Parents used a range of information sources to obtain their knowledge on management of fever; however, due to issues of trust with these sources, reassurance was often sought from healthcare practitioners. There was a desire amongst most parents for initiatives to be introduced which provide general information on how to manage fever in children. CONCLUSION: Parents were very concerned when their child was febrile and instigated practices obtained from accessible information sources. This study has identified a need for specific and reliable information initiatives to be introduced as a means of reducing parental concern and ensuring evidence-based strategies for managing a child with fever. PMID- 26280910 TI - Visual Acuity Testing Using a Random Method Visual Acuity Application. AB - BACKGROUND: A visual acuity (VA) testing application for the iPad(r) (Apple, Cupertino, CA) tablet computer using the mirroring technique was developed that randomly presented letters categorized by cognoscibility. The aim of this study was to assess whether measurements of distance VA using this application were in agreement with existing standard clinical tests of VA in adults with normal vision. MATERIALS AND METHODS: Forty-three normally sighted subjects were tested using the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart. The log minutes of arc (logMAR) VA results were compared with those from the iPad-based application, which contains a Snellen chart, a Tumbling E chart, a Landolt C chart, and a VA chart consisting of Arabic figures. After a 10-min break, subjects were retested with each test in the same order. Agreement was assessed by determining the 95% limits of agreement +/- 1.96 standard deviation of the differences between tests. RESULTS: The logMAR VA showed no significant difference between the ETDRS chart and the iPad Snellen chart (p = 0.66) and iPad Arabic figure chart (p = 0.29). The logMAR VA of the ETDRS chart was significantly better than that of the iPad Tumbling E chart (p < 0.01) or iPad Landolt C chart (p < 0.01). The subjects showed chart letter memory of the ETDRS chart (p < 0.05), Tumbling E chart (p = 0.03), and Landolt C chart (p = 0.001) but not of the iPad Snellen chart (p = 0.62) and iPad Arabic figure chart (p = 0.12). CONCLUSIONS: The iPad-based application of VA charts showed similar repeatability and may be a rapid and convenient alternative to some existing measures. The mirroring technique provides portability and accessibility for VA charts. PMID- 26280911 TI - Bimodal emotion congruency is critical to preverbal infants' abstract rule learning. AB - Extracting general rules from specific examples is important, as we must face the same challenge displayed in various formats. Previous studies have found that bimodal presentation of grammar-like rules (e.g. ABA) enhanced 5-month-olds' capacity to acquire a rule that infants failed to learn when the rule was presented with visual presentation of the shapes alone (circle-triangle-circle) or auditory presentation of the syllables (la-ba-la) alone. However, the mechanisms and constraints for this bimodal learning facilitation are still unknown. In this study, we used audio-visual relation congruency between bimodal stimulation to disentangle possible facilitation sources. We exposed 8- to 10 month-old infants to an AAB sequence consisting of visual faces with affective expressions and/or auditory voices conveying emotions. Our results showed that infants were able to distinguish the learned AAB rule from other novel rules under bimodal stimulation when the affects in audio and visual stimuli were congruently paired (Experiments 1A and 2A). Infants failed to acquire the same rule when audio-visual stimuli were incongruently matched (Experiment 2B) and when only the visual (Experiment 1B) or the audio (Experiment 1C) stimuli were presented. Our results highlight that bimodal facilitation in infant rule learning is not only dependent on better statistical probability and redundant sensory information, but also the relational congruency of audio-visual information. A video abstract of this article can be viewed at https://m.youtube.com/watch?v=KYTyjH1k9RQ. PMID- 26280912 TI - Inguinoscrotal herniation of the ureter: Description of five cases. AB - INTRODUCTION: Descent of the ureter into the inguinal canal or scrotum is rare but undoubtedly underreported. Most known cases were recognized at the time of surgery for hernia repair. We encountered five cases recently. PRESENTATION OF CASE: We reviewed the records and CT images of five patients with inguinal hernias containing a segment of the ureter. All of our cases, like most reported cases, featured obese adult males. Our cases had different outcomes, ranging from inadvertent injury of the displaced ureter to correction of the anomaly at the time of hernia repair. DISCUSSION: In all of our cases, the affected ureter was displaced anteriorly from the psoas muscle by greater than 1cm at the level of the L4 vertebra on abdominal CT. This association has not been previously described. CONCLUSION: Pre-operative diagnosis by CT can prevent injury to the ureter. We hypothesize that anterior displacement of the ureter at the level of L4 as seen on CT may be predictive of inguinoscrotal herniation of the ureter. PMID- 26280913 TI - Ultrafast STR Separations on Short-Channel Microfluidic Systems for Forensic Screening and Genotyping. AB - There are situations in which it is important to quickly and positively identify an individual. Examples include suspects detained in the neighborhood of a bombing or terrorist incident, individuals detained attempting to enter or leave the country, and victims of mass disasters. Systems utilized for these purposes must be fast, portable, and easy to maintain. DNA typing methods provide the best biometric information yielding identity, kinship, and geographical origin, but they are not portable and rapid. This study details the development of a portable short-channel microfluidic device based on a modified Agilent 2100 bioanalyzer for applications in forensic genomics. The system utilizes a denaturing polymer matrix with dual-channel laser-induced fluorescence and is capable of producing a genotype in 80 sec. The device was tested for precision and resolution using an allelic ladder created from 6 short tandem repeat (STR) loci and a sex marker (amelogenin). The results demonstrated a precision of 0.09-0.21 bp over the entire size range and resolution values from 2.5 to 4.1 bp. Overall, the results demonstrate the chip provides a portable, rapid, and precise method for screening amplified short tandem repeats and human identification screening. PMID- 26280915 TI - Response to Dr. XinQi Dong. PMID- 26280914 TI - Quantification of the Contact Area at the Head-Stem Taper Interface of Modular Hip Prostheses. AB - Corrosion of modular taper junctions of hip implants may be associated with clinical failure. Taper design parameters, as well as the intraoperatively applied assembly forces, have been proposed to affect corrosion. Fretting corrosion is related to relative interface shear motion and fluid ingress, which may vary with contact force and area. It was hypothesised in this study that assembly forces modify the extent and distribution of the surface contact area at the taper interface between a cobalt chrome head and titanium stem taper with a standard threaded surface profile. Local abrasion of a thin gold coating applied to the stem taper prior to assembly was used to determine the contact area after disassembly. Profilometry was then used to assess permanent deformation of the stem taper surface profile. With increasing assembly force (500 N, 2000 N, 4000 N and 8000 N) the number of stem taper surface profile ridges in contact with the head taper was found to increase (9.2+/-9.3%, 65.4+/-10.8%, 92.8+/-6.0% and 100%) and the overall taper area in contact was also found to increase (0.6+/-0.7%, 5.5+/-1.0%, 9.9+/-1.1% and 16.1+/-0.9%). Contact was inconsistently distributed over the length of the taper. An increase in plastic radial deformation of the surface ridges (-0.05+/-0.14 MUm, 0.1+/-0.14 MUm, 0.21+/-0.22 MUm and 0.96+/-0.25 MUm) was also observed with increasing assembly force. The limited contact of the taper surface ridges at lower assembly forces may influence corrosion rates, suggesting that the magnitude of the assembly force may affect clinical outcome. The method presented provides a simple and practical assessment of the contact area at the taper interface. PMID- 26280916 TI - Near Room Temperature, Fast-Response, and Highly Sensitive Triethylamine Sensor Assembled with Au-Loaded ZnO/SnO2 Core-Shell Nanorods on Flat Alumina Substrates. AB - Chemiresistive gas sensors with low power consumption, fast response, and reliable fabrication process for a specific target gas have been now created for many applications. They require both sensitive nanomaterials and an efficient substrate chip for heating and electrical addressing. Herein, a near room working temperature and fast response triethylamine (TEA) gas sensor has been fabricated successfully by designing gold (Au)-loaded ZnO/SnO2 core-shell nanorods. ZnO nanorods grew directly on Al2O3 flat electrodes with a cost-effective hydrothermal process. By employing pulsed laser deposition (PLD) and DC sputtering methods, the construction of Au nanoparticle-loaded ZnO/SnO2 core/shell nanorod heterostructure is highly controllable and reproducible. In comparison with pristine ZnO, SnO2, and Au-loaded ZnO, SnO2 sensors, Au-ZnO/SnO2 nanorod sensors exhibit a remarkably high and fast response to TEA gas at working temperatures as low as 40 degrees C. The enhanced sensing property of the Au ZnO/SnO2 sensor is also discussed with the semiconductor depletion layer model introduced by Au-SnO2 Schottky contact and ZnO/SnO2 N-N heterojunction. PMID- 26280917 TI - Energy Status Characteristics of Porcine Oocytes During In Vitro Maturation is Influenced by Their Meiotic Competence. AB - The characteristics of energy status in porcine oocytes as related to their meiotic competence and in vitro maturation were studied. Cycling pubertal gilts in the early luteal to early follicular phases of the ovarian cycle were used as oocyte donors. The oocytes recovered from medium (MF) or small follicles (SF) were considered meiotically more or less competent, respectively. A half of oocytes from each category was matured by the standard protocol. The oocytes were examined before or after maturation by confocal microscopy, a bioluminescent cell assay and Western blotting. Four experiments, each in triplicate, were performed to assess both SF and MF oocytes in terms of metabolic units formed by mitochondria and lipids, ATP and lipid consumption and lipid droplets with adipose differentiation-related protein (ADRP) expression. The proportion of oocytes with metabolic units, the mean ATP content and the number of lipid droplets per oocyte, and the relative number of lipid droplets with ADRP expression were significantly higher in the MF compared to SF oocytes before maturation. On the other hand, after maturation, there was an increase in the proportion of oocytes with metabolic units and the relative number of lipid droplets with ADRP expression in the SF compared to MF oocytes. In conclusion, specific differences in energy characteristics between porcine oocytes with different meiotic competence were found. Meiotically more competent oocytes are more advanced in terms of energy reserves before maturation, while meiotically less competent oocytes are more active in replenishing energy stores during maturation. PMID- 26280918 TI - An Automated and Intelligent Medical Decision Support System for Brain MRI Scans Classification. AB - A wide interest has been observed in the medical health care applications that interpret neuroimaging scans by machine learning systems. This research proposes an intelligent, automatic, accurate, and robust classification technique to classify the human brain magnetic resonance image (MRI) as normal or abnormal, to cater down the human error during identifying the diseases in brain MRIs. In this study, fast discrete wavelet transform (DWT), principal component analysis (PCA), and least squares support vector machine (LS-SVM) are used as basic components. Firstly, fast DWT is employed to extract the salient features of brain MRI, followed by PCA, which reduces the dimensions of the features. These reduced feature vectors also shrink the memory storage consumption by 99.5%. At last, an advanced classification technique based on LS-SVM is applied to brain MR image classification using reduced features. For improving the efficiency, LS-SVM is used with non-linear radial basis function (RBF) kernel. The proposed algorithm intelligently determines the optimized values of the hyper-parameters of the RBF kernel and also applied k-fold stratified cross validation to enhance the generalization of the system. The method was tested by 340 patients' benchmark datasets of T1-weighted and T2-weighted scans. From the analysis of experimental results and performance comparisons, it is observed that the proposed medical decision support system outperformed all other modern classifiers and achieves 100% accuracy rate (specificity/sensitivity 100%/100%). Furthermore, in terms of computation time, the proposed technique is significantly faster than the recent well-known methods, and it improves the efficiency by 71%, 3%, and 4% on feature extraction stage, feature reduction stage, and classification stage, respectively. These results indicate that the proposed well-trained machine learning system has the potential to make accurate predictions about brain abnormalities from the individual subjects, therefore, it can be used as a significant tool in clinical practice. PMID- 26280919 TI - Niche and Neutral Processes Together Determine Diversity Loss in Response to Fertilization in an Alpine Meadow Community. AB - Fertilization via nutrient deposition and agricultural inputs is one of the most important factors driving decreases in plant diversity. However, we still do not fully understand which processes (niche process or neutral process) are more important in leading to decreases in plant diversity caused by fertilization. A hypothesis-based approach was used to test the relative importance of niche versus neutral processes along a fertilization gradient in an alpine meadow community on the eastern Tibetan plateau, China. Niche overlap values were calculated for species biomass, and the null model was used to generate the values of niche overlap expected at random. A linear regression modeling was used to evaluate the relationship between functional traits (specific leaf area, leaf dry matter content, and leaf total nitrogen concentration) and species relative abundance. Our results demonstrated that observed niche overlap for species biomass was significantly higher than expected at lower fertilization gradients. Moreover, we also found a significantly negative correlation between species relative abundance and specific leaf area and leaf dry matter content, but a significantly positive correlation between relative abundance and leaf nitrogen concentration at lower fertilization gradients. However, these relationships were not significant at higher fertilization gradients. We concluded that community assembly is dynamic progression along the environmental gradients, and niche and neutral processes may together determine species diversity loss in response to fertilization. PMID- 26280920 TI - Linked pyridinyl-thiadiazoles: Design and synthesis as potential candidate for treatment of XDR and MDR tuberculosis. AB - Multi-drug resistant (MDR) and extremely drug resistant (XDR) Mycobacterium tuberculosis strains have turned tuberculosis (TB) as "on the verge of eradication" to "most life threatening" disease. Furthermore, synergy with HIV and other immunosuppressive disease have strengthened its prevalence. This research reports small molecule anti-infectives which are specifically potent against several strains and isolates of TB. The hit compound 7f has also proved to be active against almost 25 clinical isolates comparable to marketed anti-TB agents. PMID- 26280921 TI - Synthesis and in vitro antitumor evaluation of betulin acid ester derivatives as novel apoptosis inducers. AB - Nineteen betulin derivatives modified at the C-3 and C-28 positions were synthesized and assessed for antitumor activities against the MGC-803, PC3, Bcap 37, A375, and MCF-7 human cancer cell lines in vitro by MTT assay. Some derivatives (compounds 3a-3d and 5) displayed strong antitumor properties, with IC50 values between 4 and 18 MUM. Compound 3c, containing piperidine group at C 28 position, had IC50 values of 4.3, 4.5, 5.2, 7.5, and 5.2 MUM on the five cancer cell lines, respectively. Subsequent fluorescence staining and flow cytometric analysis indicated that compound 3c induced apoptosis in MGC-803 cell line, with an apoptosis ratio of 31.11% after 36 h of treatment at 10 MUM 3c. PMID- 26280922 TI - Synthesis, cytotoxicity and inhibition of NO production of ivangustin enantiomer analogues. AB - The eight novel ivangustin enantiomer analogues possessing alpha-methylene-gamma butyrolactone moiety have been synthesized using (4S6R, 4S6S)-4-tert butyldimethylsilyloxy-6-methylcyclohex-2-en-1-one (1) as starting material. These transformations were mainly carried out by aldol condensation reaction and one pot annelation procedure. The stereochemistry of these synthesized analogues was determined by NOE analysis. Their cytoxicity was evaluated against the human cancer cell lines HCT-116 (colon), HL-60 (leukemia), QGY-7701 (liver), SMMC-7721 (liver), A549 (lung), MCF-7 (breast). The results showed that these analogues were more selective against the cell lines HL-60 and QGY-7701. Analogue 17 exhibited potent cytotoxicity and high selectivity toward HL-60 cell line with IC50 value of 1.02 MUM, which suggested that it might be a promising anti-cancer lead compound. The inhibitory activities against NO production and the cytotoxicities in RAW 264.7 macrophages were determined at the same time. All of the analogues significantly inhibited the NO production with IC50 value in the range of 3.44-6.99 MUM. Analogues 17, 22, 23 and 7 showed higher cytotoxicities, indicated their inhibitory activities against NO production may be influenced by the cytotoxicities. PMID- 26280923 TI - Recent Advances in Platinum (IV) Complex-Based Delivery Systems to Improve Platinum (II) Anticancer Therapy. AB - Cisplatin and its platinum (Pt) (II) derivatives play a key role in the fight against various human cancers such as testicular, ovarian, head and neck, lung tumors. However, their application in clinic is limited due to dose- dependent toxicities and acquired drug resistances, which have prompted extensive research effort toward the development of more effective Pt (II) delivery strategies. The synthesis of Pt (IV) complex is one such an area of intense research fields, which involves their in vivo conversion into active Pt (II) molecules under the reducing intracellular environment, and has demonstrated encouraging preclinical and clinical outcomes. Compared with Pt (II) complexes, Pt (IV) complexes not only exhibit an increased stability and reduced side effects, but also facilitate the intravenous-to-oral switch in cancer chemotherapy. The overview briefly analyzes statuses of Pt (II) complex that are in clinical use, and then focuses on the development of Pt (IV) complexes. Finally, recent advances in Pt (IV) complexes in combination with nanocarriers are highlighted, addressing the shortcomings of Pt (IV) complexes, such as their instability in blood and irreversibly binding to plasma proteins and nonspecific distribution, and taking advantage of passive and active targeting effect to improve Pt (II) anticancer therapy. PMID- 26280924 TI - Tracking of crystalline-amorphous transition of carvedilol in rotary spun microfibers and their formulation to orodispersible tablets for in vitro dissolution enhancement. AB - Physicochemical characterization of microfibers including powder X-ray diffraction, differential scanning calorimetry, attenuated total reflectance Fourier transform infrared spectroscopy, and positron annihilation spectroscopy were used to track the crystalline-amorphous transition of carvedilol during formulation and stability testing. The applied methods unanimously indicated the amorphous transition of carvedilol in the course of rotary spinning, furthermore a supramolecular ordering of chains of polymer matrix was revealed out by positron annihilation spectroscopy. The accelerated stability study (40+/-2 degrees C/75+/-5% RH, for 4 weeks) indicated a large stress tolerance capacity of fibers, since only a partial crystallization of the active compound was observable at the last sampling point. To demonstrate possible utilization of microfibers, orodispersible tablets containing 10mg of carvedilol were successfully prepared by direct compression applying common tableting excipients. All of the investigated tablet parameters (hardness, friability, in vitro disintegration time) complied with the pharmacopoeial requirements. The performed dissolution (pH 1.0 and 6.8) study indicated that the drug dissolution from the microfiber based formula was rapid, complete and independent from the pH of the applied media, while the dissolution from the control tablets, containing crystalline carvedilol was incomplete and was strongly influenced by the pH of the applied media. PMID- 26280925 TI - Exploring in vitro, in vivo metabolism of mogroside V and distribution of its metabolites in rats by HPLC-ESI-IT-TOF-MS(n). AB - Mogroside V, a cucurbitane-type saponin, is not only the major bioactive constituent of traditional Chinese medicine Siraitiae Fructus, but also a widely used sweetener. To clarify its biotransformation process and identify its effective forms in vivo, we studied its metabolism in a human intestinal bacteria incubation system, a rat hepatic 9000g supernatant (S9) incubation system, and rats. Meanwhile, the distribution of mogroside V and its metabolites was also reported firstly. Seventy-seven new metabolites, including 52 oxidation products formed by mono- to tetra- hydroxylation/dehydrogenation, were identified with the aid of HPLC in tandem with ESI ion trap (IT) TOF multistage mass spectrometry (HPLC-ESI-IT-TOF-MS(n)). Specifically, 14 metabolites were identified in human intestinal bacteria incubation system, 4 in hepatic S9 incubation system, 58 in faeces, 29 in urine, 14 in plasma, 34 in heart, 33 in liver, 39 in spleen, 39 in lungs, 42 in kidneys, 45 in stomach, and 51 in small intestine. The metabolic pathways of mogroside V were proposed and the identified metabolic reactions were deglycosylation, hydroxylation, dehydrogenation, isomerization, glucosylation, and methylation. Mogroside V and its metabolites were distributed unevenly in the organs of treated rats. Seven bioactive metabolites of mogroside V were identified, among which mogroside IIE was abundant in heart, liver, spleen and lung, suggesting that it may contribute to the bioactivities of mogroside V. Mogroside V was mainly excreted in urine, whereas its metabolites were mainly excreted in faeces. To our knowledge, this is the first report that a plant constituent can be biotransformed into more than 65 metabolites in vivo. These findings will improve understanding of the in vivo metabolism, distribution, and effective forms of mogroside V and congeneric molecules. PMID- 26280926 TI - Analytical and statistical comparability of generic enoxaparins from the US market with the originator product. AB - Low-molecular-weight heparins (LMWHs) are complex anticoagulant drugs, made from heparin porcine mucosa starting material. Enoxaparin sodium manufactured by Sanofi is one of the most widely prescribed LMWHs and has been used since 1993 in the USA. In 2010, US Food and Drug Administration approval for supplying generic enoxaparin was granted to Sandoz and subsequently to Amphastar. Little is known, however, of the differences in composition of these preparations. In this study, samples from several batches of generic enoxaparins were purchased on the US market and analyzed with state of the art methodologies, including disaccharide building blocks quantification, nuclear magnetic resonance (NMR), and a combination of orthogonal separation techniques. Direct high-performance liquid chromatography analysis of the different enoxaparin batches revealed distinct process fingerprints associated with each manufacturer. Disaccharide building block analysis showed differences in the degree of sulfation, the presence of glycoserine derivatives, as well as in proportions of disaccharides. Results were compared by statistical approaches using multivariate analysis with a partial least squares discriminant analysis methodology. The variations were statistically significant and allowed a clear distinction to be made between the enoxaparin batches according to their manufacturer. These results were further confirmed by orthogonal analytical techniques, including NMR, which revealed compositional differences of oligosaccharides both in low- and high-affinity antithrombin fractions of enoxaparin. PMID- 26280927 TI - Modeling of Methane Migration in Shallow Aquifers from Shale Gas Well Drilling. AB - The vertical portion of a shale gas well, known as the "tophole" is often drilled using an air-hammer bit that may introduce pressures as high as 2400 kPa (350 psi) into groundwater while penetrating shallow aquifers. A 3-D TOUGH2 model was used to simulate the flow of groundwater under the high hydraulic heads that may be imposed by such trapped compressed air, based on an observed case in West Virginia (USA) in 2012. The model realizations show that high-pressure air trapped in aquifers may cause groundwater to surge away from the drill site at observable velocities. If dissolved methane is present within the aquifer, the methane can be entrained and transported to a maximum distance of 10.6 m per day. Results from this study suggest that one cause of the reported increase in methane concentrations in groundwater near shale gas production wells may be the transport of pre-existing methane via groundwater surges induced by air drilling, not necessarily direct natural gas leakage from the unconventional gas reservoir. The primary transport mechanisms are advective transport of dissolved methane with water flow, and diffusive transport of dissolved methane. PMID- 26280928 TI - A 4-week study of four 3-monochloropropane-1,2-diol diesters on lipid metabolism in C57BL/6J mice. AB - 3-Monochloropropane-1,2-diol (3-MCPD) esters have been detected in many foods, which have become a new safety issue worldwide. In the study, we investigated the effect of four 3-MCPD diesters (palmitate diester: CDP; stearate diester: CDS; oleate diester: CDO; linoleate diester: CDL) on lipid metabolism in C57BL/6J mice. The results showed that CDP, CDS, CDO and CDL significantly increased the serum TC, LDL-C levels and liver TG, TC levels at dose of 16.5MUmol/kg/day. These results indicated that 3-MCPD diesters could potentially cause hyperlipidemia in C57BL/6J mice. Moreover, oil red O staining confirmed fat accumulation in liver induced by 3-MCPD diesters. Our work will provide more information for safety evaluation of 3-MCPD diesters. However, whether free 3-MCPD or free fatty acids or combined action compensates for the hyperlipidemia effects should be elucidated in the future. PMID- 26280929 TI - Kolaviron protects against benzo[a]pyrene-induced functional alterations along the brain-pituitary-gonadal axis in male rats. AB - Exposure to benzo[a]pyrene (B[a]P) is well reported to be associated with neurological and reproductive dysfunctions. The present study investigated the influence of kolaviron, an isolated biflavonoid from the seed of Garcinia kola, on functional alterations along the brain-pituitary-gonadal axis in male rats exposed to B[a]P. Benzo[a]pyrene was orally administered at a dose of 10mg/kg alone or orally co-administered with kolaviron at 100 and 200mg/kg for 15 consecutive days. Administration of B[a]P significantly (p<0.05) decreased plasma levels of pituitary hormones namely follicle-stimulating hormone (FSH) and prolactin but increased luteinizing hormone (LH) by 47%, 55% and 20.9%, respectively, when compared with the control. The significant decrease in gonadosomatic index (GSI) was accompanied by significant decrease in testosterone production and sperm functional parameters in the B[a]P-treated rats. Moreover, B[a]P-treated rats showed significant elevation in the circulatory concentrations of pro-inflammatory cytokines and oxidative stress indices in the brain, testes and sperm of B[a]P-treated rats. Light microscopy revealed severe necrosis of the Purkinje cells in the cerebellum, neuronal degeneration of the cerebral cortex, neuronal necrosis of the hippocampus and testicular atrophy in B[a]P-treated rats. Kolaviron co-treatment significantly ameliorated B[a]P mediated damages by suppressing pro-inflammatory mediators and enhancing the antioxidant status, neuroendocrine function, sperm characteristics and improving the architecture of the brain and testes in B[a]P-treated rats. The findings in the present investigation highlight that kolaviron may be developed to novel therapeutic agent against toxicity resulting from B[a]P exposure. PMID- 26280930 TI - It is not all black and white: Future incidence of stomach cancer will be substantially higher than projected due to the effects of immigration and increasing Hispanic and Asian populations in the United States. PMID- 26280931 TI - Memory engram storage and retrieval. AB - A great deal of experimental investment is directed towards questions regarding the mechanisms of memory storage. Such studies have traditionally been restricted to investigation of the anatomical structures, physiological processes, and molecular pathways necessary for the capacity of memory storage, and have avoided the question of how individual memories are stored in the brain. Memory engram technology allows the labeling and subsequent manipulation of components of specific memory engrams in particular brain regions, and it has been established that cell ensembles labeled by this method are both sufficient and necessary for memory recall. Recent research has employed this technology to probe fundamental questions of memory consolidation, differentiating between mechanisms of memory retrieval from the true neurobiology of memory storage. PMID- 26280932 TI - Erratum to: Fluid challenges in intensive care: the FENICE study: A global inception cohort study. PMID- 26280933 TI - What is new in selective decontamination of the digestive tract? PMID- 26280936 TI - Proton Conduction Study on Water Confined in Channel or Layer Networks of La(III)M(III)(ox)3.10H2O (M = Cr, Co, Ru, La). AB - Proton conduction of the La(III)M(III) compounds, LaM(ox)3.10H2O (abbreviated to LaM; M = Cr, Co, Ru, La; ox(2-) = oxalate) is studied in view of their networks. LaCr and LaCo have a ladder structure, and the ladders are woven to form a channel network. LaRu and LaLa have a honeycomb sheet structure, and the sheets are combined to form a layer network. The occurrence of these structures is explained by the rigidness versus flexibility of [M(ox)3](3-) in the framework with large La(III). The channel networks of LaCr and LaCo show a remarkably high proton conductivity, in the range from 1 * 10(-6) to 1 * 10(-5) S cm(-1) over 40 95% relative humidity (RH) at 298 K, whereas the layer networks of LaCr and LaCo show a lower proton conductivity, ~3 * 10(-8) S cm(-1) (40-95% RH, 298 K). Activation energy measurements demonstrate that the channels filled with water molecules serve as efficient pathways for proton transport. LaCo was gradually converted to La(III)Co(II)(ox)2.5.4H2O, which had no channel structure and exhibited a low proton conductivity of less than 1 * 10(-10) S cm(-1). The conduction-network correlation of LaCo(ox)2.5.4H2O is reported. PMID- 26280937 TI - An update on RNA-targeting therapies for neuromuscular disorders. AB - PURPOSE OF REVIEW: Antisense-mediated modulation of transcripts is a dynamic therapeutic field, especially for neuromuscular disorders. RECENT FINDINGS: For three diseases, this approach has advanced to the clinical trial phase, that is Duchenne muscular dystrophy, spinal muscular atrophy and myotonic dystrophy. In parallel, numerous proof-of-concept studies in cell and animal models have been reported for additional neuromuscular disorders. SUMMARY: This review discusses the most notable advances in preclinical and clinical studies in the past year. For Duchenne muscular dystrophy, spinal muscular atrophy and myotonic dystrophy trials are ongoing to assess safety and efficacy, while in parallel preclinical studies are being conducted to identify ways to improve efficiency and delivery. For other neuromuscular diseases, progress is made as well warranting future clinical trials. However, towards clinical trial readiness, it is important not only to optimize the therapy preclinically but to also develop the infrastructure that is needed to conduct trials. PMID- 26280938 TI - Duchenne muscular dystrophy: clinical trials and emerging tribulations. AB - PURPOSE OF REVIEW: This article reviewed the most recent clinical trials investigating potential treatments for Duchenne muscular dystrophy (DMD). In the development of these studies, investigators have encountered unexpected challenges that reveal limitations in our understanding of the clinical trial design for this disease. RECENT FINDINGS: Recent clinical trials for DMD have revealed limitations in our understanding of the natural history of this disease. As a result of these revelations, there has been a significant effort to document the natural history of Duchenne and develop valid outcome measure that could be used in clinical trials in different subsets of patients. SUMMARY: Treatment for DMD is a rapidly changing field. Some of the drugs that are currently under investigation will receive Food and Drug Administration approval in the near future. These would become part of clinical practice. This article summarizes the different therapeutic approaches under investigation and illustrates the importance of defining sound research methods that are specific to the disease and population under investigation. PMID- 26280940 TI - General Ambient Temperature Benzylic Metalations Using Mixed-Metal Li/K-TMP Amide. AB - Highly regioselective benzylic metalations in hydrocarbon solvent have been achieved at rt and 0 degrees C using a mixed-metal Li/K-TMP amide comprised of KOtBu, BuLi, and 2,2,6,6,-tetramethylpiperidine (TMP(H)). Mixing of KOtBu, BuLi, and TMP(H) in heptane gave a solution of the base mixture which when used in deuterium labeling experiments confirmed the requirement of the three reagent components for both reactivity and selectivity. The reaction protocol is operationally straightforward and found to be applicable to a broad range of substrates. Upon generation of the metalated products, they are reacted in heptane at ambient temperature in a variety of synthetically useful ways. Illustrated examples include generation of the benzyltrimethylsilanes and alpha,alpha-bis(trimethylsilyl)toluenes reagents, which are bench-stable surrogates of benzyl anions and alpha-silyl carbanions utilized for nucleophilic addition and Peterson olefination reactions. Direct C-C couplings mediated by 1,2 dibromoethane provided entries into bibenzyls and [2.2]metacyclophanes. Comparison of reaction outcomes with the same reactions carried out in THF at -78 degrees C showed no negative effects for conducting the reactions under these milder more user-friendly conditions. PMID- 26280939 TI - Changes in Copper, Zinc, and Malondialdehyde Levels and Superoxide Dismutase Activities in Pre-Eclamptic Pregnancies. AB - BACKGROUND: Preeclampsia (PE) is a hypertensive disorder that occurs in 2% to 8% of pregnancies. Although numerous studies have investigated the etiology and pathophysiology of preeclampsia, the precise pathological mechanisms remain poorly understood. Hence, in the present study malondialdehyde (MDA) levels and SOD expression, and Cu and Zn concentrations and ratios were correlated with birth weights in pregnant women with and without PE, and in non-pregnant females of reproductive age. MATERIAL AND METHODS: Malondialdehyde (MDA) levels and superoxide dismutase (SOD) activities were determined spectrophotometrically, and Cu and Zn levels were determined using atomic absorption spectrometry in serum from 42 non-pregnant women (NP), 40 healthy pregnant women (HP), and 38 pre eclamptic pregnant (PE) women. Subsequently, Cu/Zn ratios were calculated and associations with birth weights were analyzed using Spearman correlations. RESULTS: Cu, Zn, and MDA levels and Cu/Zn ratios were significantly higher in the PE group than in the HP and NP groups, and were significantly higher in the HP than in the NP group (p<0.001 and p<0.001; respectively). In contrast, serum Zn and SOD levels were significantly lower in the PE group than in HP and NP groups, and were significantly lower in the HP group than in the NP group (p<0.001 and p<0.001; respectively). However, only Cu and Zn levels were significantly associated with fetal birth weights (r=-0.433, p<0.001). CONCLUSIONS: Serum Cu/Zn ratios may reflect vascular complications of PE, and the ensuing increases in lipid peroxidation may play important pathogenic roles. PMID- 26280941 TI - Recyclable lanthanide-functionalized MOF hybrids to determine hippuric acid in urine as a biological index of toluene exposure. AB - A lanthanide-functionalized MOF with extremely high water tolerance was developed as a fluorescent probe for hippuric acid (HA) in urine which is considered as the biological indicators of toluene exposure. For the first time, the urinary HA was detected by fluorescence spectrometry based on a recyclable Ln-MOF sensor. PMID- 26280942 TI - Bioconjugated Hydrogels for Tissue Engineering and Regenerative Medicine. AB - Hydrogels are hydrophilic polymer networks with high water content, which have played an important role as scaffolds for cells, as carriers for various biomolecules (e.g., drugs, genes, and soluble factors), and as injectable biomaterials in tissue engineering (TE) and regenerative medicine. Bioconjugation is an approach for improving the performance of hydrogels using cell-responsive components, such as proteins and peptides, which have high affinity to regulate cellular behaviors and tissue morphogenesis. However, the current knowledge on the role of those bioconjugated moieties in controlling cellular functions and tissue morphogenesis and bioconjugation methods are limited in the context of TE and organogenesis. Moreover, micro- and nanofabrication techniques have been used to manipulate bioconjugated hydrogels for regulating cell behaviors and function. This Review therefore describes synthesis, characteristics, and manipulation of various bioconjugated hydrogels and their potential in TE applications with special emphasis on preclinical/clinical translation. PMID- 26280943 TI - Solution-Processed Transistors Using Colloidal Nanocrystals with Composition Matched Molecular "Solders": Approaching Single Crystal Mobility. AB - Crystalline silicon-based complementary metal-oxide-semiconductor transistors have become a dominant platform for today's electronics. For such devices, expensive and complicated vacuum processes are used in the preparation of active layers. This increases cost and restricts the scope of applications. Here, we demonstrate high-performance solution-processed CdSe nanocrystal (NC) field effect transistors (FETs) that exhibit very high carrier mobilities (over 400 cm(2)/(V s)). This is comparable to the carrier mobilities of crystalline silicon based transistors. Furthermore, our NC FETs exhibit high operational stability and MHz switching speeds. These NC FETs are prepared by spin coating colloidal solutions of CdSe NCs capped with molecular solders [Cd2Se3](2-) onto various oxide gate dielectrics followed by thermal annealing. We show that the nature of gate dielectrics plays an important role in soldered CdSe NC FETs. The capacitance of dielectrics and the NC electronic structure near gate dielectric affect the distribution of localized traps and trap filling, determining carrier mobility and operational stability of the NC FETs. We expand the application of the NC soldering process to core-shell NCs consisting of a III-V InAs core and a CdSe shell with composition-matched [Cd2Se3](2-) molecular solders. Soldering CdSe shells forms nanoheterostructured material that combines high electron mobility and near-IR photoresponse. PMID- 26280944 TI - Effect of Presymptomatic Body Mass Index and Consumption of Fat and Alcohol on Amyotrophic Lateral Sclerosis. AB - IMPORTANCE: Because dietary intake may influence pathophysiologic mechanisms in sporadic amyotrophic lateral sclerosis (ALS), the association between premorbid dietary intake and the risk of sporadic ALS will provide insight into which mechanisms are possibly involved in ALS pathophogenesis. OBJECTIVE: To systematically determine the association between premorbid dietary intake and the risk of sporadic ALS. DESIGN, SETTING, AND PARTICIPANTS: A population-based case control study was conducted in a general community setting in the Netherlands from January 1, 2006, to September 30, 2011. Analysis was conducted April 1, 2013, to November 15, 2014. All patients with a new diagnosis of possible, probable (laboratory supported), or definite ALS according to the revised El Escorial criteria were included and multiple sources were used to ensure complete case ascertainment. Of 986 eligible patients, 674 gave informed consent and returned a complete questionnaire; 2093 controls randomly selected from the general practitioners' registers and frequency matched to the patients for sex and age were included. MAIN OUTCOMES AND MEASURES: We studied the premorbid intake of nutrients in association with the risk of ALS by using a 199-item food frequency questionnaire adjusted for confounding factors and corrected for multiple comparisons while minimizing recall bias. RESULTS: Presymptomatic total daily energy intake in patients, reported as mean (SD), was significantly higher compared with controls (2258 [730] vs 2119 [619] kcal/day; P < .01), and presymptomatic body mass index (calculated as weight in kilograms divided by height in meters squared) was significantly lower in patients (25.7 [4.0] vs 26.0 [3.7]; P = .02). With values reported as odds ratio (95% CI), higher premorbid intake of total fat (1.14; 1.07-1.23; P < .001), saturated fat (1.43; 1.25-1.64; P < .001), trans-fatty acids (1.03; 1.01-1.05; P < .001), and cholesterol (1.08; 1.05-1.12; P < .001) was associated with an increased risk of ALS; higher intake of alcohol (0.91; 0.84-0.99; P = .03) was associated with a decreased risk of ALS. These associations were independent of total energy intake, age, sex, body mass index, educational level, smoking, and lifetime physical activity. No significant associations between dietary intake and survival were found. CONCLUSIONS AND RELEVANCE: The combination of independent positive associations of a low premorbid body mass index and a high fat intake together with prior evidence from ALS mouse models transgenic for SOD1 and earlier reports on premorbid body mass index support a role for increased resting energy expenditure before clinical onset of ALS. PMID- 26280945 TI - Flavonoid-rich orange juice is associated with acute improvements in cognitive function in healthy middle-aged males. AB - PURPOSE: Epidemiological evidence suggests that chronic consumption of fruit based flavonoids is associated with cognitive benefits; however, the acute effects of flavonoid-rich (FR) drinks on cognitive function in the immediate postprandial period require examination. The objective was to investigate whether consumption of FR orange juice is associated with acute cognitive benefits over 6 h in healthy middle-aged adults. METHODS: Males aged 30-65 consumed a 240-ml FR orange juice (272 mg) and a calorie-matched placebo in a randomized, double blind, counterbalanced order on 2 days separated by a 2-week washout. Cognitive function and subjective mood were assessed at baseline (prior to drink consumption) and 2 and 6 h post consumption. The cognitive battery included eight individual cognitive tests. A standardized breakfast was consumed prior to the baseline measures, and a standardized lunch was consumed 3 h post-drink consumption. RESULTS: Change from baseline analysis revealed that performance on tests of executive function and psychomotor speed was significantly better following the FR drink compared to the placebo. The effects of objective cognitive function were supported by significant benefits for subjective alertness following the FR drink relative to the placebo. CONCLUSIONS: These data demonstrate that consumption of FR orange juice can acutely enhance objective and subjective cognition over the course of 6 h in healthy middle-aged adults. PMID- 26280947 TI - Skin-to-Skin Contact: A Comforting Place With Comfort Food. AB - Birth and the newborn environment are stressful, especially for preterm infants who have to contend with medical conditions while adapting to the extrauterine world. Therefore, preterm newborns are excellent candidates for comforting measures. Skin-to-skin contact is the best way to provide comfort in several of the realms of Kolcaba's Comfort Theory. Evidence suggests that skin-to-skin contact between the mother and newborn changes the discomforting newborn environment into one that is profoundly comforting. Skin-to-skin contact promotes infant physiologic stability and warmth, helps in organizing infant sleep, reduces stress and pain, and makes breast milk readily available. Comfort to the newborn can be effectively accomplished by skin-to-skin contact. PMID- 26280946 TI - L-Arginine supplementation does not enhance blood flow and muscle performance in healthy and physically active older women. AB - PURPOSE: The purpose of this study was to examine the effects of acute L-arginine (L-arg) supplementation on peripheral vasodilatation and muscle performance in older women. METHODS: In a double-blind, randomized, placebo-controlled study, 20 elderly women were randomly assigned in a double-blind fashion to either an L-arg (ARG, N = 10) or placebo (PLA, N = 10) group. During the first visit, both groups underwent a Doppler ultrasound exam (to assess the femoral artery vasodilatation) at rest (baseline), and immediately before and after the isokinetic strength test (performed at 80 min after supplementation). On the second and third visits, the groups completed a battery of muscle performance tests (to assess the isometric and functional strength), initiated at the same time point (80 min after supplementation). RESULTS: The femoral artery blood flow (ARG: 443.9 +/- 42.8 vs. PLA: 373.1 +/- 40.8 ml/min; P > 0.05) and area (ARG: 0.45 +/- 0.03 vs. PLA: 0.41 +/- 0.02 cm(2); P > 0.05) were similar between the groups at basal conditions, and they remained unchanged after supplementation. Following exercise, blood flow increased ~160 % above the basal level, and there was no significant (P > 0.05) difference between the ARG and PLA groups. Additionally, there were no significant (P > 0.05) differences between the ARG and PLA groups for any strength variable (isokinetic, isometric, and functional). CONCLUSION: These results show that acute L-arg supplementation provides no ergogenic effect on blood flow and muscle performance in older women. PMID- 26280948 TI - Short and long-term phototoxicity in cells expressing genetic reporters under nanosecond laser exposure. AB - Nanosecond-duration laser pulses are exploited in a plethora of therapeutic and diagnostic applications, such as optoacoustic imaging. However, phototoxicity effects of pulsed radiation in living cells, in particular those expressing genetic reporters, are not well understood. We established a three-dimensional fluorescent protein expressing cellular model in order to reliably investigate the extent and major exposure parameters responsible for both photobleaching and phototoxicity under pulsed laser exposure, unveiling a variety of possible effects on living cells, from reversible photobleaching to cytotoxicity and cell death. Significant losses of fluorescence levels were identified when exposing the cells to illumination conditions considered safe under common standards for skin exposure in diagnostic imaging applications. Thus, the use of photolabile fluorescent proteins and their in vivo exposure parameters have to be designed carefully for all applications using pulsed nanosecond radiation. In particular, loss of signal due to bleaching may significantly alter signals in longitudinal measurements, making data quantification challenging. PMID- 26280949 TI - Urethral tissue regeneration using collagen scaffold modified with collagen binding VEGF in a beagle model. AB - Extensive urethral defects have a serious impact on quality of life, and treatment is challenging. A shortage of material for reconstruction is a key limitation. Improving the properties of biomaterials and making them suitable for urethral reconstruction will be helpful. Previously, we constructed a fusion protein, collagen-binding VEGF (CBD-VEGF), which can bind to collagen scaffold, stimulate cell proliferation, and promote angiogenesis and tissue regeneration. We proposed that CBD-VEGF could improve the performance of collagen in reconstruction of extensive urethral defects. Our results showed that collagen scaffolds modified with CBD-VEGF could promote urethral tissue regeneration and improve the function of the neo-urethra in a beagle extensive urethral defect model. Thus, modifying biomaterials with bioactive factors provides an alternative strategy for the production of suitable biomaterials for urethral reconstruction. PMID- 26280950 TI - Single-layer tungsten oxide as intelligent photo-responsive nanoagents for permanent male sterilization. AB - Permanent male sterilization has been recognized as useful tools for the development of neuter experimental animals and fattening livestock, as well as efficient control of pet overpopulation. Traditional routes such as surgical ways, chemical injections, and anti-fertility vaccines have addressed these crucial problems with idea outcomes. However, these routes usually bring out serious pain and infection towards animals, as well as induce long-term adverse reaction and immune suppression. Thus, a convenient, but non-surgical strategy for male sterilization under a mild manner is highly desirable. Here, for the first time, we demonstrate a novel platform for male sterilization by using single-layer WO2.72 nanosheets as smart photo-responsive sterilants. Upon a 980 nm irradiation, these nanoagents can possess intrinsic NIR-induced hyperthermia and sensitize the formation of singlet oxygen due to the cooperation of photothermal and photodynamic effects. Mechanism of cellular injury can be attributed to the denaturation of protein and apoptosis-related death. Moreover, long-term toxicity and possible metabolism route after testicular injection are discussed, indicating the neglectable systemic toxicity and high bio compatibility of our nanoagents. Overall, our strategy can extremely overcome the shortcomings in various routine routes and suggest the new biological application of nanomaterials. PMID- 26280952 TI - Role of motor end plate-targeted Botulinum toxin type A injections in children with cerebral palsyitle. AB - Botulinum toxin type A (BTX) injections are frequently used in children with cerebral palsy (CP) to control spasticity. Injection variables still lead to variable outcomes of this treatment. Using instrumented spasticity assessment and muscle volume assessment the most effective location of the injection was demonstrated for gracilis and psoas muscles in children with CP. It was found that this treatment is most effective when injected in the motor endplate zones of the selected muscles. This review article presents all available research on the role of motor endplate-targeting of BTX injections in children with CP. PMID- 26280953 TI - Surgical treatment of the adult acquired flexible flatfoot. AB - In this review article, the authors give an overview of the currently available soft tissue and bony procedures in the treatment of the adult acquired flexible flatfoot. Instead of starting from the classification for posterior tibial tendon dysfunction, described by Johnson and Storm, the authors address the flatfoot from a more anatomical point of view. Based on this, they will try to define a treatment algorithm. PMID- 26280954 TI - Antibiotic-loaded bone cement in total joint arthroplasty. AB - Periprosthetic joint infection is a devastating complication after total joint replacement. Prevention is mandatory and systemic antibiotic prophylaxis is nowadays a recognized cornerstone. Further addition of local antibiotics eluting from bone cement is a real possibility but its routine use is controversial. Pros and cons of its routine use in primary and revision total joint arthroplasty will be discussed. Cement spacers carrying high doses of antibiotic(s) are currently accepted during two-stage treatment of infected prosthetic joints. Several issues such as alternatives to classic antibiotics, optimal dosages and others will also be explored. PMID- 26280951 TI - MRI evaluation of injectable hyaluronic acid-based hydrogel therapy to limit ventricular remodeling after myocardial infarction. AB - Injectable biomaterials are an attractive therapy to attenuate left ventricular (LV) remodeling after myocardial infarction (MI). Although studies have shown that injectable hydrogels improve cardiac structure and function in vivo, temporal changes in infarct material properties after treatment have not been assessed. Emerging imaging and modeling techniques now allow for serial, non invasive estimation of infarct material properties. Specifically, cine magnetic resonance imaging (MRI) assesses global LV structure and function, late gadolinium enhancement (LGE) MRI enables visualization of infarcted tissue to quantify infarct expansion, and spatial modulation of magnetization (SPAMM) tagging provides passive wall motion assessment as a measure of tissue strain, which can all be used to evaluate infarct properties when combined with finite element (FE) models. In this work, we investigated the temporal effects of degradable hyaluronic acid (HA) hydrogels on global LV remodeling, infarct thinning and expansion, and infarct stiffness in a porcine infarct model for 12 weeks post-MI using MRI and FE modeling. Hydrogel treatment led to decreased LV volumes, improved ejection fraction, and increased wall thickness when compared to controls. FE model simulations demonstrated that hydrogel therapy increased infarct stiffness for 12 weeks post-MI. Thus, evaluation of myocardial tissue properties through MRI and FE modeling provides insight into the influence of injectable hydrogel therapies on myocardial structure and function post-MI. PMID- 26280955 TI - Hand disorders associated with diabetes: a review. AB - The diabetes may cause damage many structures and organs of a human body and predispose to secondary disorders, including involvement of the hand. Carpal tunnel syndrome, trigger finger or Dupuytren's disease occur more frequently in diabetic patients as well as other, poorer recognized conditions such as limited joint mobility, or hand weakness. The paper presents these disorders, emphasizes differences in clinical presentation, methods and outcomes of treatment, comparing to the non-diabetic patients. Although there are not call complications, some evidence suggests that they may be, as their prevalence is related to the duration of the diabetes, poor metabolic control and occurrence of other disorders such as retino- and nephropathy. PMID- 26280956 TI - Efficacy of hip resurfacing arthroplasty: 6 year results from an international multisurgeon prospective cohort study. AB - Metal-on-metal hip resurfacing is undertaken worldwide. This procedure helps preserve femoral bone stock and allows patients to return to high activity sports. Most outcome studies are individual surgeon case series from single centers where the results and outcomes are evaluated by the same surgeon. One method of increasing the external validity of a follow-up study is to have a multi-centre study design with independent assessment of the outcomes. We present an independent assessment of eleven year follow-up of hip resurfacing outcomes from an international hip resurfacing register. The purpose of this study was to assess: Implant survival at maximum follow-up for revision due to any reason, implant survival at maximum follow-up for revision due to major causes of failure, hip function following hip resurfacing and factors affecting hip function, effect of gender and age on hip function and implant survival, effect of femoral component size on hip function and implant survival. 4535 patients (5000 hips) entered into the registry during 1997-2002 were studied. In summary, at a maximum follow-up of 11 years hip resurfacing has a good implant survival of 96.2% and excellent post-operative function. This is excellent given the international and multisurgeon nature of this cohort where majority of the surgeons were in their learning curve. PMID- 26280957 TI - Unusual localizations of unicameral bone cysts and aneurysmal bone cysts: A retrospective review of 451 cases. AB - Unicameral bone cysts (UBC) and aneurysmal bone cysts (ABC) are benign cystic lesions of bone which are easily diagnosed. However, unusual locations may lead to a false diagnosis. Therefore the aim of this retrospective study was to determine the frequency of unusual localizations. The authors studied 451 cases with histopathologically confirmed diagnosis of UBC or ABC, seen between 1981 and 2012. In the UBC group (352 cases) humerus, femur and calcaneus were found to be the most common sites, while acetabulum, scapula, scaphoid, lunatum, metacarpals, metatarsals, toe phalanges and ulna each accounted for less than 1%. In the ABC group (99 cases) the most common sites of involvement were femur, humerus and tibia, while finger phalanges, ilium, acetabulum, pubis, calcaneus, cuboid, and toe phalanges each accounted for only 1%. The differential diagnosis of cystic bone lesions should include both UBC and ABC. Pain complaints plead for the latter, except in case of fracture. PMID- 26280958 TI - Comparison of surgical treatments for mucous cysts of the distal interphalangeal joint. AB - Mucous cysts of the interphalangeal joints are common. Several surgical techniques have been described, but none has proven to be superior. We compared three techniques that entail complete removal of the cyst together with the concomitant osteophytes. In group A wound closure was obtained by full thickness skin graft, in group B by primary closure and in group C by a local skin graft. Sixty-four patients with 70 cysts were reviewed. An overall recurrence rate of 8.6% was observed. Forty-five of the studied patients received a full thickness skin graft (4 out of 45 recurred), 23 were closed primarily (2 out of 23 recurred) and 2 by a local skin graft (no recurrences). Full thickness skin graft showed no significant higher recurrence compared to primary closure. Full thickness skin graft showed no significant higher pain or satisfaction compared to primary closure. Patients with a recurrent cyst were less satisfied and had more pain than those without recurrences. PMID- 26280959 TI - Radiological predictive factors for the outcome of surgically treated calcaneus fractures. AB - Calcaneus fractures are fairly common and clinically relevant due to their poor outcome. Thus, solving the controversy regarding treatment and outcome prediction should be a target. This study intends to evaluate the predictive ability of common radiologic tools for the surgical outcome of calcaneus fractures, regardless of treatment modality. 44 patients' records, with operated calcaneus fractures between 2008 and 2013, were retrospectively assessed and imagiology was blindly evaluated. Patients were submitted to percutaneous or open lateral approach. No relevant correlations were found between the measurements on the plain lateral radiograph and the outcome. Fractures were also graded according to the Sanders classification. Type 4 fractures predicted the occurrence of any hazard, such as skin or pain related complications and need for secondary surgery (p=0.051, odds=14.00 [CI=1.30-150.89]). However, it's still not possible to accurately target patients with high risk of postoperative complications. Until then, follow-up protocols should be maintained indiscriminately. PMID- 26280960 TI - Long-term follow-up of a cemented titanium stem. AB - We present the outcome of 270 cemented titanium alloy femoral stems. These patients were followed up annually both clinically and radiologically, and were included up until their last follow-up. 120 patients completed a 10-year follow up. The 10-year survival of the Ultima Straight Stem cemented femoral component (defined by revision of the femoral stem) was 90.1% (95% CI=84.0-94.0%), with aseptic loosening being the major reason for failure. The preoperative Harris Hip Score improved from 35.3 to 79.3 at 10 years. There were 17 cases of stem subsidence, radiolucent lines in 11 hips, 5 cases of cement fracture and 18 hips had osteolysis in 2 adjacent Gruen zones. This is the largest study in the English literature of this implant, and reflects UK district general hospital practice with surgery performed by a variety of surgical grades and via different surgical approaches. Although the outcome of this implant was within the previous standard set by the National Institute for Health and Clinical Excellence and is comparable to other series of titanium stems, it is inferior to that of more modern cemented and uncemented implants, and falls outside the new NICE recommendation of <5% revision rate at ten year. As a result this implant is no longer used in our institution, and it has also now been withdrawn from the market. We suggest that patients with this implant should be followed up radiologically due to the relatively high rate of stem subsidence and lucency between the cement and prosthesis, to identify those who may be at risk of failure. PMID- 26280961 TI - Outcomes of bilateral sacroiliac joint fusions and the importance of understanding potential coexisting lumbosacral pathology that might also require surgical treatment. AB - Only one study in the literature describes performing a bilateral sacroiliac joint fusion, and the results were poor. Many patients needing a bilateral sacroiliac joint fusion frequently have had previous lumbosacral surgeries and present with lumbosacral pain as well. This study reviews our results in consecutive patients having had a bilateral sacroiliac joint fusion over a five year period. Fifteen patients had bilateral sacroiliac joint fusions with 13 having concurrent lumbosacral fusions. The modified posterior midline fascial splitting approach, first described by Belanger was utilized. Patients were followed for an average of 30.3 months. There were no infections, neurovascular injuries, lasting morbidity or deaths. One non-union of a sacroiliac joint (7%) occurred, which after revision was satisfactory. There was a statistically significant drop in pain (p=0.01488) using the VAS, and patient satisfaction rates were 86%. With all those patients saying they would have the surgery again for the same result. There was no significant increase in functionality. Patients needing bilateral sacroiliac joint fusions frequently fall into the "failed back" category, and it is important to evaluate both the sacroiliac joints and the lumbosacral spine for potential pain generators. This study shows that by treating all the pain generators in both areas there were significant decreases in pain, low complications, low re-operation rates, and high patient satisfaction scores. Overall functionality, however, was not positively affected. PMID- 26280962 TI - The effect of the intercondylar notch width index on anterior cruciate ligament injuries: a study on groups with unilateral and bilateral ACL injury. AB - BACKGROUND: To evaluate the relationship of the intercondylar notch width with unilateral and bilateral ACL injury by using MR images. MATERIAL AND METHODS: The intercondylar notch width index was measured on the MR images of 18 patients with a bilateral ACL injury, 38 patients with a unilateral ACL injury and 53 healthy subjects with a normal ACL and the results of all groups were compared with each other. RESULTS: The mean NWI values were 0,227 (+/-0.008) in bilateral injured; 0,245 (+/-0.009) in unilateral injured and 0,272 (+/-0.01) in control groups and 0,251(+/-0.01) in unaffected side of the unilateral group. There were statistically significant differences in intercondylar notch width index (NWI) values between all groups and there was a significant difference between the affected and the unaffected sides in group with unilateral ACL injury. A cutoff value of 0.25 for NWI gave an odds ratio of 26.5 for bilateral and 3.23 for unilateral ACL injuries. CONCLUSIONS: The finding that NWI is significantly narrowed in patients with bilateral and unilateral ACL tears compared with the healthy controls suggest a relationship between a narrow NWI and an increased risk of ACL injury. The patients with a narrow NWI should also be screened contralaterally for assessment of ACL injury risk on the other knee. So, specialized training programmes for the people with narrow NWI can be prepared for preventing ACL injuries. PMID- 26280963 TI - A new compression design that increases proximal locking screw bending resistance in femur compression nails. AB - The aim is to present our new method of compression, a compression tube instead of conventional compression screw and to investigate the difference of proximal locking screw bending resistance between compression screw application (6 mm wide contact) and compression tube (two contact points with 13 mm gap) application. We formed six groups each consisting of 10 proximal locking screws. On metal cylinder representing lesser trochanter level, we performed 3-point bending tests with compression screw and with compression tube. We determined the yield points of the screws in 3-point bending tests using an axial compression testing machine. We determined the yield point of 5 mm screws as 1963+/-53 N (mean+/-SD) with compression screw, and as 2929+/-140 N with compression tubes. We found 51% more locking screw bending resistance with compression tube than with compression screw (p=0,000). Therefore compression tubes instead of compression screw must be preferred at femur compression nails. PMID- 26280964 TI - One-year follow-up of platelet-rich plasma infiltration to treat chronic proximal patellar tendinopathies. AB - Infiltration of Platelet-Rich Plasma (PRP) may be considered as a recent therapeutic option for chronic tendinopathies. The aim of this study is to evaluate the clinical status and the return to sports activities in patients with chronic proximal patellar tendinopathies. Twenty subjects with chronic proximal patellar tendinopathy benefited from 1 infiltration of PRP coupled with a standardized eccentric rehabilitation. The follow-up (up to 1 year) was assessed by means of a Visual Anologue Scale (VAS), the International Knee Documentation Committee (IKDC) form and the Victorian Institute of Sport Assessment (VISA-P) score. Moreover, subjects had to answer an information questionnaire concerning their life and sports activities. Seventy percents of the patients reported a favourable evolution with decrease of pain, and returned to sports activities. With time, VAS dropped significantly and both IKDC and VISA-P scores improved also significantly. This study confirms that a local injection of PRP coupled with a program of eccentric rehabilitation for treating a chronic jumper's knee, improves pain symptoms and the functionalities of the subjects' knee up to 1 year after injection. PMID- 26280965 TI - The Muller acetabular reinforcement ring--still an option in acetabular revision of Paprosky 2 defects? Longterm results after 10 years. AB - BACKGROUND: Aim of this study was to measure the clinical and radiological longterm outcome after acetabular revision arthroplasty (RTHA) using the Muller acetabular reinforcement ring. MATERIAL AND METHODS: 86 patients with 90 revision arthroplasties and a mean age of 68 years (41 to 84) were included. The mean follow-up was 10 years (range 7-12). The Harris Hip Score and the WOMAC Index were used to assess pain and functional outcome. Furthermore clinical examination of range of motion and radiologic examinations were performed in 34 patients. RESULTS: The radiologic analysis reports no signs of loosening in 79%, 15% showed possibly loosening and 6% probable loosening. Definite radiologic loosening has not been detected. In the meantime 12 patients (13.3%) of 90 revision total hip arthroplasty underwent a revision of the acetabulum with change of the acetabular component which means a survival rate of 86.7% after 10 years follow-up. The mean center of rotation of the hip moved 0.15 cm (SD 0.74 cm) laterally and 0.1 cm (SD 0.97 cm) cranially based on the geometrically reconstructed center of rotation. A mean score of 58 points for the Harris Hip Score (range 14-93) indicated a poor functional outcome, while a mean value of 96 points (range 0-223) for the WOMAC Index indicated good results for functional outcome in daily living. CONCLUSIONS: The revision arthroplasty in cases with acetabular defects using the Muller acetabular reinforcement ring shows acceptable longterm results. LEVEL OF EVIDENCE: Level IV. PMID- 26280966 TI - Mid-term results for hip resurfacing in patients under 30 years old with childhood hip disorders. AB - The aim of our study was to assess survivorship and function in young patients with hip resurfacing for degenerative arthritis secondary to childhood hip diseases. Data was collected retrospectively using the institutional database and patient notes. Between 1999 and 2012, there were 156 hip resurfacings performed in 143 patients (82 females, 73 males). Mean age at the time of surgery was 21.4 years (12.3 to 30.0). The main indications for surgery included; DDH, AVN, Perthes' and SUFE. Median follow-up was 4.1 years (1.0 to 13.2). Median Oxford scores improved from 54.2 pre-op to 18.8 post-op at a minimum of 2 years follow up. There were 14 failures. Median head size was 46 mm (45 mm in the failures) For the failures, median cup inclination was 44.4 degrees and anteversion 7.6 degrees. We report the largest single surgeon series of resurfacing hip arthroplasty in the under 30's for childhood hip disorders. 90% 5-year survivorship and good functional outcome can be achieved. PMID- 26280967 TI - Grade 3C open femur fractures with vascular repair in adults. AB - Grade 3C open femur fractures are challenging injuries with higher rates of complications. This is a retrospective review of grade 3C open femur fractures with vascular repair between 2002 and 2012. Outcomes included initial MESS score, additional injuries, duration of operation, complications, secondary operations or amputations, and social life implications. Thirty-one of 39 total patients were selected for revascularization and fracture fixation based on soft tissue injury and MESS score. The intra-operative approach included temporary arterial shunt replacement, orthopedic fixation, arterial reconstruction venous and/or nerve repair and routine fasciotomies. An external fixation and reverse saphenous vein graft was used in a majority of the patients (respectively; 93.5%, 90.3%). The mean follow up was 5.4 years (range 2.2-10). The decision to amputate versus salvage should be left up to patients and their care teams after discussing options and future possibilities rather than using a scoring system. PMID- 26280968 TI - The young patient and the medial unicompartmental knee replacement. AB - PURPOSE: Younger patients with unicompartmental degenerative knee joint diseases present a therapeutic dilemma. The purpose of this study is to evaluate the long term results of the Oxford phase III unicompartmental knee replacement through a minimally invasive approach in the young patient. METHODS: We have studied a total of 51 patients (59 interventions) who underwent the Oxford Phase III Unicompartmental Knee Replacement. A clinical, radiographical and functional evaluation was performed twelve years after intervention. RESULTS: According to the American Knee Society Score using Insall's criteria overall results of unicompartmental knee arthroplasty showed an excellent or good outcome for 53 knees (96.36%), fair for 1 (1.81%) and poor for 1 (1.81%) in the postoperative long term. The survival rate of the implants was close to 95% at follow-up. CONCLUSIONS: Twelve years follow-up results of UKA through a minimally invasive exposure in young patients demonstrate predictably good outcomes. PMID- 26280969 TI - Injuries in male versus female soccer players: epidemiology of a nationwide study. AB - The aim of this study is to analyse soccer injuries on a national scale over one decade and to compare injury rates by gender. Detailed injury data obtained from the Royal Belgian Football Association from seasons 1999-2000 and 2009-2010 were recorded and gender differences in incidences of injuries, type of injury, affected body part and timing of injury were compared. A significant decrease in injuries from 7.56 to 5.96 injuries per 100 players was seen (p<0.0001). Overall male players sustained more cont usions, fractures, joint dislocations and musculotendinous injuries than female players. Proportionally, females sustained more severe injuries than men (p<0.0001). Significantly more injuries where sustained during competition in both males and females. The number of injuries in male and female soccer players has decreased over the past decade. A higher injury rate was seen in men but proportionally, females sustained more severe injuries. PMID- 26280970 TI - Treatment of mallet fracture using a percutaneous fixation technique with an 18 gauge needle. AB - The purpose of this paper is to introduce a simple and intuitive treatment method using an 18-gauge needle for mallet fractures that involve more than one-third of the articular surface. We performed a retrospective review of 17 patients who underwent closed reduction using an 18-gauge needle with transfixation of Kirschner wire between March 2007 and October 2013. According to the Wehbe and Schneider classification, 15 cases were type IB, 1 was type IIB, and 1 was type IIC. The mean size of bony fragments at the time of injury was 53 percent of the articular surface of the distal phalanx. According to Crawford's criteria, 6 of 17 patients had an excellent result, 9 had a good result and 2 had fair results. Our method of percutaneous reduction using an 18-gauge needle with transfixation of Kirschner wire is minimally invasive and is useful for the fixation of mallet fractures. PMID- 26280971 TI - A retrospective analysis of osteochondroma of scapula following excision biopsy. AB - Scapula is an uncommon site for osteochondroma. There is a paucity of information regarding postoperative complications, recurrence of osteochondroma, functional improvement. A retrospective analysis of 9 patients treated for osteochondroma scapula over a period of 4 years was undertaken to assess postoperative complications, recurrence, and functional improvement following excision biopsy for osteochondroma scapula. All patients of any age group who were diagnosed with osteochondroma scapula and treated with excision biopsy in the past 6 years were included in the study. Patients were followed up for recurrence, postoperative complications and functional assessment using modified UCLA shoulder rating scale. The mean age at presentation was 13.7 years. Boys were more commonly affected than girls with a male to female ratio of 7:2. There was no incidence of recurrence of osteochondroma, postoperative wound complications or functional limitation following excision biopsy of osteochondroma scapula. We conclude that preoperative functional restriction in osteochondroma of scapula is mainly due to location of tumour especially when present over ventral or ventromedial aspect scapula. After complete excision they do not cause any functional limitations. PMID- 26280972 TI - Measurement of ulnar variance and radial inclination on X-rays of healed distal radius fractures. With the axis of the distal radius or ulna? AB - Ulnar variance and radial inclination are radiological parameters frequently used to evaluate displacement of distal radius fractures. In most studies measurements are based on the long central axis of the distal radius, although the axis of the distal ulna can also be used. The purpose of this study was to determine which axis is more reliable. Four observers performed measurements on standard anteroposterior digital wrist X-rays of 20 patients taken 1 and 2 months after sustaining an extra-articular distal radius fracture. Intraobserver reliability was similar with both methods. No difference was found in interobserver reliability between both methods for ulnar variance, but for radial inclination it was better with the axis through the radius. Measurements on two X-rays of the same wrist taken at a different moment were similar with both methods. It can be concluded that the central axis of the distal radius can remain the basis to determine ulnar variance and radial inclination. PMID- 26280973 TI - Platelet-Rich-Plasma injection seems to be effective in treatment of plantar fasciitis: a case series. AB - Plantar fasciitis is the most common cause of heel pain. Diverse non-operative treatment options are available. The purpose of this study was to determine if a single platelet-rich-plasma injection at the origin of the plantar fascia in patients with plantar fasciitis gives a functional improvement. Patients with plantar fasciitis and failed conservative treatment were included in this retrospective study. Included patients were sent four questionnaires after platelet-rich-plasma injection. Primary outcome is functional improvement, determined by foot function index in which lower scores correlates with a better foot function. A total of 61 feet in 58 patients were included. The median foot function index before treatment was 69.4 and after treatment 31.8, which is a significant decrease. In 80.3% of the patients the foot function index decreased. Therefore platelet-rich-plasma injection seems to be effective in treatment of patients with plantar fasciitis when conservative treatment failed. PMID- 26280974 TI - Evaluation of current treatment techniques for distal radius fractures amongst Belgian orthopaedic surgeons. AB - This online questionnaire was initiated to investigate if a consensus on the treatment of distal radius fractures amongst orthopaedic surgeons in Belgium exist. Two cases were presented: an extra-articular fracture, with dorsal displacement (Frykman type I) and a displaced intra-articular fracture (Frykman type VII). Treatment of choice and rationale of choice were investigated. 158 responses were collected. In case of a Frykman type I, the majority of surgeons would have performed a closed reduction and intrafocal K-wiring (37.3%) or volar plating (34.8%). In case of a Frykman type VII, volar plating was the primary treatment of choice (66.5%), closed reduction and K-wiring was chosen in 24.7% and external fixation in 4.4%. We cannot conclude on a consensus in treatment choice amongst Belgian orthopaedic surgeons. Compared to previous research, an increase in the use of volar plating in intra- as well as in extra-articular distal radius fractures was noticed. PMID- 26280975 TI - A descriptive study on the surgery and the microbiology of Gustilo type III fractures in an university hospital in Switzerland. AB - OBJECTIVE: To describe the epidemiology, the surgical treatment, the microbiology, the antibiotic prophylaxis and the outcome of patients with the most severe type of open fractures. METHODS: Retrospective chart reviews of patients with Gustilo type III open fracture admitted to an university hospital in Switzerland between January 2007 and December 2011. The patient's and fracture's characteristics, surgery, antibiotic prophylaxis, and microbiology findings at the initial and at the revision surgery were described. RESULTS: Thirty patients were included (83% male, mean age 41 years). More than half of the patients had polytrauma. In all patients, debridement and stabilization surgery (70% using external fixation) were performed at admission. Soft tissue reconstruction was performed in 87% and in 23% immediate bone graft was performed. Antibiotic prophylaxis were given in all patients for a median duration of 9 days (60% received amoxicillin/clavulanic acid). Positive bacterial culture was found in 53% of the patients at initial surgery and in 88% at revision surgery. At initial and revision surgery, 47% and 88% of the pathogens were amoxicillin/clavulanic acid-resistant. Treatment outcome was favorable in 24 of 30 patients (80%) and in six cases (20%) an amputation had to be performed. None of the patients had chronic bone infection. CONCLUSIONS: Positive cultures were found often in open fractures. Amoxicillin/clavulanic acid which is often mentioned in many guidelines as prophylaxis in open fractures does not cover the most common isolated organisms. The combination of surgery and antibiotic prophylaxis leads to good outcome in Gustilo type III fracture. PMID- 26280976 TI - Minimally invasive unicompartmental knee arthroplasty in treatment of osteonecrosis versus osteoarthritis: a matched-pair comparison. AB - This study was conducted to compare the differences of the outcome and surgical technique for minimally invasive unicompartmental knee arthroplasty(UKA) in treatment of osteonecrosis versus osteoarthritis. Twenty-nine spontaneous osteonecrosis of the knee (SONK) cases were reviewed retrospectively. An equal number of patients with osteoarthritis (OA) performed in the same period were selected and matched with respect to age, preoperative range of motion and radiological grade of knee arthrosis. The mean follow up time were 44.14+/-14.05 and 44.45+/-14.45 months, respectively. The preoperative hospital for special surgery knee score and visual analogue score were significantly better in group OA than those of group SONK. However, the results were comparable in terms of postoperative pain, knee score, range of motion and axial alignment. From a technical point of view, the osteonecrosis stage and bone defect must be taken into account when using UKA for SONK. PMID- 26280977 TI - A novel freehand method for patellar resurfacing in total knee replacement. AB - Patellar resurfacing in the context of primary total knee replacement (TKR) and in the presence of patella-femoral osteoarthritis is common and widespread practice, as it reduces the rate of re-operation and anterior knee pain. There are several measuring devices and cutting jigs available in the market, which aim to aid with accurately resecting the patellar articular surface. A common characteristic of these jigs is that the patella needs to be everted at some stage to apply them and use them. The senior author of this paper has developed a method of performing patellar resection with the use of simple instruments with no need to evert it and while it engages the trochlea in a physiological position. We propose that this method is reproducible and produces cuts that are parallel to the trochlea. PMID- 26280978 TI - Preventing mechanical complications of hip spacer implantation: technical tips and pearls. AB - Periprosthetic joint infection is a frequent complication after total hip replacement. Two-stage exchange with the use of a temporary cement spacer is commonplace. Several complications are possible with its use. In addition to infection persistence, mechanical complications such as dislocation or fractures are among the most common. Several risk factors can and should be addressed during first stage or spacer implantation surgery in order to minimize complications. Technical aspects as well as practical tips and pearls to overcome common nuisances such as spacer instability or femoral and acetabular bone loss will be discussed. PMID- 26280979 TI - Males in Dietetics, What Can Be Learned from the Nursing Profession? A Narrative Review of the Literature. AB - In Canada 95% of dietitians are female despite serving a sex-diverse population. Literature examining why there are so few male dietitians is limited. However, nursing, like dietetics, is female dominated but has a large body of literature examining sex diversity within the profession. Therefore, a narrative literature review was conducted to find articles that examined the following questions: (i) What are the barriers and motivating factors for prospective male nursing students? and (ii) What are the perceived sex-based challenges that male nursing students encounter during their education? A total of 38 articles were included in the final review and the results are presented under the following headings: barriers, motivators, and educational experiences both in the classroom and during clinical rotations. The review outlines the current state of knowledge regarding sex as it relates to nursing and how this information compares with the current dietetics literature. Conclusions and recommendations are drawn about what changes could be made in dietetic education immediately and how further research could provide insight towards reducing the barriers and facilitating easier access to dietetics education for males. PMID- 26280980 TI - Assessment of endothelial function and myocardial flow reserve using (15)O-water PET without attenuation correction. AB - PURPOSE: Myocardial blood flow (MBF) measurement using positron emission tomography (PET) from the washout rate of (15)O-water is theoretically independent of tissue attenuation. The aim of this study was to evaluate the impact of not using attenuation correction in the assessment of coronary endothelial function and myocardial flow reserve (MFR) using (15)O-water PET. METHODS: We retrospectively processed 70 consecutive (15)O-water PET examinations obtained at rest and during cold pressor testing (CPT) in patients with dilated cardiomyopathy (n = 58), or at rest and during adenosine infusion in heart transplant recipients (n = 12). Data were reconstructed with attenuation correction (AC) and without attenuation correction (NAC) using filtered backprojection, and MBF was quantified using a single compartmental model. The agreement between AC and NAC data was assessed using Lin's concordance correlation coefficient followed by Bland-Altman plot analysis. RESULTS: Regarding endothelial function, NAC PET showed poor reproducibility and poor agreement with AC PET data. Conversely, NAC PET demonstrated high reproducibility and a strong agreement with AC PET for the assessment of MFR. CONCLUSION: Non attenuation-corrected (15)O-water PET provided an accurate measurement of MFR compared to attenuation-corrected PET. However, non-attenuation-corrected PET data were less effective for the assessment of endothelial function using CPT in this population. PMID- 26280981 TI - Impact of PET/CT image reconstruction methods and liver uptake normalization strategies on quantitative image analysis. AB - BACKGROUND: In oncological imaging using PET/CT, the standardized uptake value has become the most common parameter used to measure tracer accumulation. The aim of this analysis was to evaluate ultra high definition (UHD) and ordered subset expectation maximization (OSEM) PET/CT reconstructions for their potential impact on quantification. PATIENTS AND METHODS: We analyzed 40 PET/CT scans of lung cancer patients who had undergone PET/CT. Standardized uptake values corrected for body weight (SUV) and lean body mass (SUL) were determined in the single hottest lesion in the lung and normalized to the liver for UHD and OSEM reconstruction. Quantitative uptake values and their normalized ratios for the two reconstruction settings were compared using the Wilcoxon test. The distribution of quantitative uptake values and their ratios in relation to the reconstruction method used were demonstrated in the form of frequency distribution curves, box-plots and scatter plots. The agreement between OSEM and UHD reconstructions was assessed through Bland-Altman analysis. RESULTS: A significant difference was observed after OSEM and UHD reconstruction for SUV and SUL data tested (p < 0.0005 in all cases). The mean values of the ratios after OSEM and UHD reconstruction showed equally significant differences (p < 0.0005 in all cases). Bland-Altman analysis showed that the SUV and SUL and their normalized values were, on average, up to 60 % higher after UHD reconstruction as compared to OSEM reconstruction. CONCLUSION: OSEM and HD reconstruction brought a significant difference for SUV and SUL, which remained constantly high after normalization to the liver, indicating that standardization of reconstruction and the use of comparable SUV measurements are crucial when using PET/CT. PMID- 26280982 TI - Tropomodulin3 as the link between insulin-activated AKT2 and cortical actin remodeling in preparation of GLUT4 exocytosis. AB - It is well established that insulin-induced remodeling of actin filaments into a cortical mesh is required for insulin-stimulated GLUT4 exocytosis. Akt2 and its downstream effectors play a pivotal role in mediating the translocation and membrane fusion of GLUT4-storage vesicle (GSV). However, the direct downstream effector underlying the event of cortical actin reorganization has not been elucidated. In a recent study in Nature Communications, (1) Lim et al identify Tropomodulin3 (Tmod3) as a downstream target of the Akt2 kinase and describe the role of this pointed-end actin-capping protein in regulating insulin-dependent exocytosis of GSVs in adipocytes through the remodeling of the cortical actin network. Phosphorylation of Tmod3 by Akt2 on Ser71 modulates insulin-induced actin remodeling, a key step for GSV fusion with the plasma membrane (PM). Furthermore, the authors establish Tm5NM1 (Tpm3.1 in new nomenclature) (2) as the cognate tropomyosin partner of Tmod3, and an essential role of Tmod3-Tm5NM1 interaction for GSV exocytosis and glucose uptake. This study elucidates a novel effector of Akt2 that provides a direct mechanistic link between Akt2 signaling and actin reorganization essential for vesicle fusion, and suggests that a subset of actin filaments with specific molecular compositions may be dedicated for the process of vesicle fusion. PMID- 26280983 TI - Nanofiber Yarn/Hydrogel Core-Shell Scaffolds Mimicking Native Skeletal Muscle Tissue for Guiding 3D Myoblast Alignment, Elongation, and Differentiation. AB - Designing scaffolds that can mimic native skeletal muscle tissue and induce 3D cellular alignment and elongated myotube formation remains an ongoing challenge for skeletal muscle tissue engineering. Herein, we present a simple technique to generate core-shell composite scaffolds for mimicking native skeletal muscle structure, which comprise the aligned nanofiber yarn (NFY) core and the photocurable hydrogel shell. The aligned NFYs are prepared by the hybrid composition including poly(caprolactone), silk fibroin, and polyaniline via a developed dry-wet electrospinning method. A series of core-shell column and sheet composite scaffolds are ultimately obtained by encapsulating a piece and layers of aligned NFY cores within the hydrogel shell after photo-cross-linking. C2C12 myoblasts are seeded within the core-shell scaffolds, and the good biocompatibility of these scaffolds and their ability to induce 3D cellular alignment and elongation are successfully demonstrated. Furthermore, the 3D elongated myotube formation within core-shell scaffolds is also performed after long-term cultivation. These data suggest that these core-shell scaffolds combine the aligned NFY core that guides the myoblast alignment and differentiation and the hydrogel shell that provides a suitable 3D environment for nutrition exchange and mechanical protection to perform a great practical application for skeletal muscle regeneration. PMID- 26280984 TI - Nano-Structured Bio-Inorganic Hybrid Material for High Performing Oxygen Reduction Catalyst. AB - In this study, we demonstrate a non-Pt nanostructured bioinorganic hybrid (BIH) catalyst for catalytic oxygen reduction in alkaline media. This catalyst was synthesized through biomaterial hemin, nanostructured Ag-Co alloy, and graphene nano platelets (GNP) by heat-treatment and ultrasonically processing. This hybrid catalyst has the advantages of the combined features of these bio and inorganic materials. A 10-fold improvement in catalytic activity (at 0.8 V vs RHE) is achieved in comparison of pure Ag nanoparticles (20-40 nm). The hybrid catalyst reaches 80% activity (at 0.8 V vs RHE) of the state-of-the-art catalyst (containing 40% Pt and 60% active carbon). Comparable catalytic stability for the hybrid catalyst with the Pt catalyst is observed by chronoamperometric experiment. The hybrid catalyst catalyzes 4-electron oxygen reduction to produce water with fast kinetic rate. The rate constant obtained from the hybrid catalyst (at 0.6 V vs RHE) is 4 times higher than that of pure Ag/GNP catalyst. A catalytic model is proposed to explain the oxygen reduction reaction at the BIH catalyst. PMID- 26280985 TI - Calculations of hyperfine coupling constant of copper(II) in aqueous environment. Finite temperature molecular dynamics and relativistic effects. AB - The presented paper is focused on the calculation of hyperfine coupling constants (HFCC) of Cu (2+) ion in water environment. To simulate the conditions of the electron paramagnetic resonance (EPR) experiment in aqueous phase, molecular dynamics using the density functional theory (DFT) was employed. In total three different functionals (BLYP, B3LYP, M06) were employed for studying their suitability in describing coordination of Cu (2+) by water molecules. The system of our interest was composed of one Cu (2+) cation surrounded by a selected number (between thirty and fifty) of water molecules. Besides the non relativistic HFCCs (Fermi contact terms) of Cu (2+) also the four-component relativistic HFCC calculations are presented. The importance of the proper evaluation of HFCCs, the inclusion of spin-orbit term, for Cu (2+) containing systems (Neese, J. Chem. Phys. 118, 3939 2003; Almeida et al., Chem. Phys. 332, 176 2007) is confirmed at the relativistic four-component level of theory. PMID- 26280987 TI - Hidden Bond Anomalies: The Peculiar Case of the Fluorinated Amine Chalcogenides. AB - Bond anomalies have been investigated for a set of 53 molecules with either N-F, Ti-P, Cr-H, Pb-C, or Pb-F bonds for which reverse rather than inverse bond length bond strength relationships have been previously claimed. The intrinsic strength of each bond investigated was determined utilizing the associated local stretching force constant obtained at the CCSD(T)/aug-cc-pVTZ level of theory. For the metal containing molecules, LC-omegaPBE calculations with the aug-cc-pVTZ (Cr, Pb) and the 6-31++G(d,p) basis set (Ti) were carried out. For bonds containing a metal atom, any bond anomaly could not be confirmed. Previously reported results were due to ill-defined bond strength descriptors or lacking accuracy. In the case of the fluoro amines, methyl fluoro amines, and the fluoro amine oxides, direct or hidden bond anomalies were detected, which result from two or more opposing electronic effects: a dominant bond shortening effect due to electron withdrawal and a bond weakening due to lone pair repulsion or hybridization defects. Bond anomalies can be disguised by a complex interplay of electronic effects. These hidden bond anomalies could be identified in this work for the fluoro amine chalcogenides. PMID- 26280986 TI - Lethal and Demographic Impact of Chlorpyrifos and Spinosad on the Ectoparasitoid Habrobracon hebetor (Say) (Hymenoptera: Braconidae). AB - The appropriate use of biological agents and chemical compounds is necessary to establish successful integrated pest management (IPM) programs. Thus, the off target effects of pesticides on biological control agents are essential considerations of IPM. In this study, the effects of lethal and sublethal concentrations of chlorpyrifos and spinosad on the demographic parameters of Habrobracon hebetor (Say) (Hymenoptera: Braconidae) were assessed. Bioassays were carried out on immature and adult stages by using dipping and contact exposure of dry pesticide residue on an inert material, respectively. The lethal concentration (LC)50 values of chlorpyrifos and spinosad were 3.69 and 151.37 ppm, respectively, on the larval stage and 1.75 and 117.37 ppm, respectively, on adults. Hazard quotient (HQ) values for chlorpyrifos and spinosad were 400 and 2.2, respectively, on the larval stage and 857.14 and 2.84, respectively, on adults. A low lethal concentration (LC30) was used to assess the sublethal effects of both pesticides on the surviving females. In each treatment, 25 survivors were randomly selected and transferred into 6-cm Petri dishes. Adults were provided daily with last instars of Anagasta kuehniella (Zeller) as a host until all of the females died. The number of eggs laid, percent of larvae hatched, longevity, and sex ratio were recorded. Stable population growth parameters were estimated by the Jackknife method. In control, chlorpyrifos, and spinosad treatments, the intrinsic rates of increase (r m) values were 0.23, 0.10, and 0.21, respectively. The results of this study suggest a relative compatibility between spinosad use and H. hebetor. Finally, further studies should be conducted under natural conditions to verify the compatibility of spinosad with H. hebetor in IPM programs. PMID- 26280988 TI - Real-life Data on Patient Characteristics, Cost and Effectiveness of Field directed Treatment for Actinic Keratoses: An Observational Study. AB - Actinic keratoses (AK) occur frequently; however, real-life clinical data on personalized treatment choice and costs are scarce. This multicentre one-year observational study investigated patient-characteristics, cost and effectiveness of methylaminolaevulinate photodynamic therapy (MAL-PDT), imiquimod (IMI) and 5 fluorour-acil (5-FU) in patients with AKs on the face/scalp. A total of 104 patients preferred MAL-PDT, 106 preferred IMI and 110 preferred 5-FU. At baseline, significant differences between treatment groups were found; most patients were severely affected (mean 32.5 AK in PDT-group, 20.2 in IMI-group, 22.8 in 5-FU-group). A mean reduction in lesions of 81% after MAL-PDT, 82% after IMI and 88% after 5-FU was found after one year. Annual costs were ?1,950 for MAL PDT, ?877 for IMI and ?738 for 5-FU. These results show that, compared with clinical trials, in the real-life clinical setting AK patients are usually more severely affected and treatment costs are much higher. Furthermore, patient characteristics are important factors in treatment choice. PMID- 26280989 TI - Self-Reported Memory Failures: Associations with Future Dementia in a Population Based Study with Long-Term Follow-Up. AB - OBJECTIVES: To examine the association between self-reported memory failures and incident dementia in individuals aged 60 and older. DESIGN: Longitudinal, community based. SETTING: Betula Prospective Cohort Study, a population-based study in Umea, Sweden. PARTICIPANTS: Individuals with a mean age of 71.5 +/- 8.8 (range 60-90) (N = 1,547). MEASUREMENTS: Participants rated the frequency of everyday memory failures using the 16-item Prospective and Retrospective Memory Questionnaire (PRMQ) and underwent objective memory testing at baseline. Participant self-reports of complaints of poor memory by family and friends were evaluated. Dementia status was followed-up for 10 to 12 years. RESULTS: Over the study period, 225 participants developed dementia (132 with Alzheimer's disease (AD)). In Cox proportional hazard regression models adjusted for demographic factors, PRMQz-scores predicted incident dementia (hazard ratio (HR) = 1.21 for all-cause dementia; HR = 1.25 for AD, Ps < .01). The significant associations remained when depressive symptoms and objective memory performance were adjusted for, when low performers on objective memory (>=1 standard deviations below the age group mean) were excluded, and in analyses with delayed entry (survival time >= 5 years). Similar patterns were observed for the prospective and retrospective subscales, although including how often participants self-reported that others complained about their poor memory eliminated the association between PRMQ scores and dementia and itself emerged as a significant predictor. CONCLUSION: Self reported memory failure predicted future dementia or AD independent of objective memory performance. Subjective reports of complaints by family and friends appear to be an even more-important indicator of preclinical impairments, and physicians should not ignore them, even in the absence of objective memory deficits. PMID- 26280990 TI - Urinalysis Orders Among Patients Admitted to the General Medicine Service. PMID- 26280992 TI - A comparative study of colorimetric cell proliferation assays in immune cells. AB - Cell proliferation assays are basic and essential techniques for assessing cellular function. Various colorimetric assays, such as MTT-, WST-1-, and resazurin-based assays, are available; however, studies directly comparing the suitability of each method for immune cell proliferation are scarce. Thus, we aimed to determine the best reagent and its optimal conditions based on variables such as cell number range, stimulation dose, kinetics, and compatibility with the cell division assay using CFSE fluorescence dye which is able to directly monitor divided cells by flow cytometry. In the absence of stimulation, MTT solubilized with SDS (MTT-SDS) and resazurin appeared to accurately reflect the cell numbers in a linear fashion. On the other hand, WST-1 exhibited a higher stimulation index following strong stimulation, whereas MTT-SDS and resazurin exhibited a better sensitivity to weak stimulation. A longer duration for stimulation did not necessarily increase sensitivity. CFSE staining revealed incremental cell division in response to anti-CD3 antibody stimulation in a dose-dependent manner. The cell numbers indirectly estimated from cell division profiles were consistent with the dose-response curve in the absorbance of MTT-SDS and resazurin. The absorbance does not increase before cell division, irrespective of T cell activation status, suggesting that these reagents reflect the cell number but not the cellular volume. Collectively, resazurin and MTT-SDS seem to be more reliable than others, and thus appear applicable in various conditions for the immune cell experiments. PMID- 26280991 TI - Mechanisms of Quality of Life and Social Support in Inflammatory Bowel Disease. AB - Cognitive and social factors are essential considerations in inflammatory bowel disease (IBD) patient management, but existing research is limited. This study aims to expand the IBD literature by examining the relationship between social supports and QoL, while examining mechanisms in these relationships. Consenting patients attending an IBD outpatient clinic were provided a survey package (N = 164). Regressions evaluated predictors of IBD-QoL, and catastrophizing and optimism were examined as mediators between social support and IBD-QoL. Diminished IBD-QoL was predicted by younger age, greater negative spousal responses, and less perceived spousal support. Mediation models showed helplessness catastrophizing to be the lone mediator, acting as a mechanism between both negative spousal responses and perceived spousal support with IBD QoL. Social interaction variables are associated with IBD-QoL, but patients' experience of helplessness acts to reduce their ability to benefit from social support. Patient care should consider supportive social and cognitive factors to improve IBD-QoL. PMID- 26280994 TI - Primary prevention of neural tube defects in Brazil: insights into anencephaly. PMID- 26280995 TI - Genetic professionals' views on genetic counsellors: a French survey. AB - The genetic counselling profession was established in France in 2004. Eight years later, 122 genetic counsellors have graduated from the unique educational French program which awards the Professional Master Degree of Human Pathology, entitled "Master of Genetic Counselling and Predictive Medicine". As part of a global evaluation of this new profession by health genetic professionals, we undertook a national survey investigating various aspects such as employment, work responsibilities and integration. To our knowledge, this is the first study to investigate the views of genetic professionals on the genetic counsellors' role. Of 422 French professionals invited to take part in this study, 126 participated. The survey underlines that this profession is significantly recognized by physicians practicing within genetics departments. French genetic counsellors are allowed to manage consultations independently, without the necessary presence of a qualified medical geneticist but under his or her responsibility. Genetic counsellors participate in a wide range of consultations. They provide both information for relevant and for genetic testing and sometimes disclose the genetic test result to patient. Eventually, the role of genetic counsellors appears to be directly dependent from the relationship of trust between the two health professions. PMID- 26280993 TI - The Future of Pharmaceutical Manufacturing Sciences. AB - The entire pharmaceutical sector is in an urgent need of both innovative technological solutions and fundamental scientific work, enabling the production of highly engineered drug products. Commercial-scale manufacturing of complex drug delivery systems (DDSs) using the existing technologies is challenging. This review covers important elements of manufacturing sciences, beginning with risk management strategies and design of experiments (DoE) techniques. Experimental techniques should, where possible, be supported by computational approaches. With that regard, state-of-art mechanistic process modeling techniques are described in detail. Implementation of materials science tools paves the way to molecular based processing of future DDSs. A snapshot of some of the existing tools is presented. Additionally, general engineering principles are discussed covering process measurement and process control solutions. Last part of the review addresses future manufacturing solutions, covering continuous processing and, specifically, hot-melt processing and printing-based technologies. Finally, challenges related to implementing these technologies as a part of future health care systems are discussed. PMID- 26280996 TI - Social determinants of family health history collection. AB - Family health history (FHH) is the most basic form of genomic information. Although public health efforts have been made to promote FHH collection, empirical data on the extent to which community residents in rural areas actively collect FHH is limited. Therefore, we examined rates of FHH collection in a community-based sample of South Carolina residents. We conducted a structured telephone survey in a random sample of black and white South Carolina residents. Respondents were asked if they had ever actively collected FHH from relatives using an item developed by the Centers for Disease Control and Prevention. Overall, 42 % of respondents reported that they had actively collected their FHH. Blacks were significantly more likely than whites to have collected their FHH in bivariate analysis, but race did not have a significant association with FHH collection in the multivariate model (OR = 1.36, 95 % CI = 0.79, 2.35, p = 0.26). The likelihood of collecting FHH was increased among respondents whose last medical visit occurred in the past year compared to those whose last medical visit was more than 1 year ago (OR = 2.00, 95 % CI = 1.12, 3.56, p = 0.02). In addition, older respondents had a reduced likelihood of collecting their FHH (OR = 0.69, 95 % CI = 0.53, 0.90, p = .01). Lastly, women were about twice as likely as men to have collected their FHH (OR = 1.83, 95 % CI = 1.12, 2.99, p = 0.02). Greater efforts are needed to increase the collection of FHH information; these efforts may need to target men, the elderly, and individuals who have not had a recent medical visit. PMID- 26280997 TI - Ad Integrum Functional and Volumetric Recovery in Right Lobe Living Donors: Is It Really Complete 1 Year After Donor Hepatectomy? AB - The partial liver's ability to regenerate both as a graft and remnant justifies right lobe (RL) living donor liver transplantation. We studied (using biochemical and radiological parameters) the rate, extent of, and predictors of functional and volumetric recovery of the remnant left liver (RLL) during the first year in 91 consecutive RL donors. Recovery of normal liver function (prothrombin time [PT] >=70% of normal and total bilirubin [TB] <=20 umol/L), liver volumetric recovery, and percentage RLL growth were analyzed. Normal liver function was regained by postoperative day's 7, 30, and 365 in 52%, 86%, and 96% donors, respectively. Similarly, mean liver volumetric recovery was 64%, 71%, and 85%; whereas the percentage liver growth was 85%, 105%, and 146%, respectively. Preoperative PT value (p = 0.01), RLL/total liver volume (TLV) ratio (p = 0.03), middle hepatic vein harvesting (p = 0.02), and postoperative peak TB (p < 0.01) were predictors of early functional recovery, whereas donor age (p = 0.03), RLL/TLV ratio (p = 0.004), and TLV/ body weight ratio (p = 0.02) predicted early volumetric recuperation. One-year post-RL donor hepatectomy, though functional recovery occurs in almost all (96%), donors had incomplete restoration (85%) of preoperative total liver volume. Modifiable predictors of regeneration could help in better and safer donor selection, while continuing to ensure successful recipient outcomes. PMID- 26280998 TI - TCF-1 upregulation identifies early innate lymphoid progenitors in the bone marrow. AB - The cellular and molecular events that drive the early development of innate lymphoid cells (ILCs) remain poorly understood. We show that the transcription factor TCF-1 is required for the efficient generation of all known adult ILC subsets and their precursors. Using novel reporter mice, we identified a new subset of early ILC progenitors (EILPs) expressing high amounts of TCF-1. EILPs lacked efficient T and B lymphocyte potential but efficiently gave rise to NK cells and all known adult helper ILC lineages, indicating that they are the earliest ILC-committed progenitors identified so far. Our results suggest that upregulation of TCF-1 expression denotes the earliest stage of ILC fate specification. The discovery of EILPs provides a basis for deciphering additional signals that specify ILC fate. PMID- 26280999 TI - Pyrethroids and Nectar Toxins Have Subtle Effects on the Motor Function, Grooming and Wing Fanning Behaviour of Honeybees (Apis mellifera). AB - Sodium channels, found ubiquitously in animal muscle cells and neurons, are one of the main target sites of many naturally-occurring, insecticidal plant compounds and agricultural pesticides. Pyrethroids, derived from compounds found only in the Asteraceae, are particularly toxic to insects and have been successfully used as pesticides including on flowering crops that are visited by pollinators. Pyrethrins, from which they were derived, occur naturally in the nectar of some flowering plant species. We know relatively little about how such compounds--i.e., compounds that target sodium channels--influence pollinators at low or sub-lethal doses. Here, we exposed individual adult forager honeybees to several compounds that bind to sodium channels to identify whether these compounds affect motor function. Using an assay previously developed to identify the effect of drugs and toxins on individual bees, we investigated how acute exposure to 10 ng doses (1 ppm) of the pyrethroid insecticides (cyfluthrin, tau fluvalinate, allethrin and permethrin) and the nectar toxins (aconitine and grayanotoxin I) affected honeybee locomotion, grooming and wing fanning behaviour. Bees exposed to these compounds spent more time upside down and fanning their wings. They also had longer bouts of standing still. Bees exposed to the nectar toxin, aconitine, and the pyrethroid, allethrin, also spent less time grooming their antennae. We also found that the concentration of the nectar toxin, grayanotoxin I (GTX), fed to bees affected the time spent upside down (i.e., failure to perform the righting reflex). Our data show that low doses of pyrethroids and other nectar toxins that target sodium channels mainly influence motor function through their effect on the righting reflex of adult worker honeybees. PMID- 26281000 TI - Interventricular septum metastasis in neuroendocrine tumour. PMID- 26281001 TI - Intensification of insulin therapy with basal-bolus or premixed insulin regimens in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. AB - The purpose of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the effect of intensified insulin regimens (basal-bolus versus premixed) on glycemic control in patients with type 2 diabetes. We conducted an electronic search until March 2015 on many electronic databases including online registries of ongoing trials. All RCTs comparing basal bolus with premixed insulin regimens, with a duration of >12 weeks and with >30 patients per arm, were included. Investigators extracted data on study characteristics, outcome measures, and methodological quality. We found thirteen RCTs lasting 16-60 weeks and involving 5255 patients assessed for the primary endpoint (reduction of HbA1c from baseline). Meta-analysis of change in HbA1c level between basal-bolus and premixed insulin regimens resulted in a small and non-significant difference of 0.09% (95% CI -0.03 to 0.21), with substantial heterogeneity between studies (I(2) = 74.4%). There was no statistically significant difference in the event rate for overall hypoglycemia (0.16 episode/patient/year, 95%CI -2.07 to 2.3), weight change (-0.21 kg, -0.164 to 0.185), and daily insulin dose (-0.54 U/day, -2.7 to 1.6). The likelihood for reaching the HbA1c <7% was 8% higher (3-13%, I(2) = 68.8%) with the basal-bolus as compared with the premixed regimen. There is no clinically relevant difference in the efficacy of basal-bolus versus premixed insulin regimens for HbA1c decrease in type 2 diabetic patients. These findings may be helpful to adapt treatment to individual patient needs. PMID- 26281002 TI - Cytotoxicity, genotoxicity and antibacterial effectiveness of a bioceramic endodontic sealer. AB - AIM: To compare the characteristics of bioceramic endodontic sealer Endosequence BC sealer with those of AH Plus sealer. METHODOLOGY: Cytotoxicity and genotoxicity were analysed on human gingival fibroblasts submitted to cell culture medium conditioned by sealers using the MTT reduction assay and micronucleus formation test (MNT), respectively. Cells grown on fresh medium served as controls. Cell viabilities were measured at 1, 3, 5 and 7 days. The antibacterial activity was analysed on an Enterococcus faecalis strain (ATCC 29212) using both on agar diffusion test (ADT) and a direct contact test (DCT). The inhibition zones in ADT were measured after 48 h and the colony-forming units counting in the DCT after 1, 24, 72 and 168 h. Data were compared by anova and Tukey's test and MNT by Fisher's exact test (P < 0.05). RESULTS: Cultures submitted to Endosequence BC sealer had a significantly higher number of viable cells (P < 0.01) and less micronucleus formation (P < 0.05) than AH Plus sealer. Endosequence BC sealer exhibited significantly smaller inhibition zones (6.00 +/- 0.03 mm) than AH Plus sealer (10.31 +/- 0.21 mm) (P < 0.05). Moreover, Endosequence BC sealer had significantly smaller antibacterial activity than AH Plus sealer up to 1 h of direct contact (P < 0.05). On other exposure times, both materials had similar antibacterial effectiveness (P > 0.05). CONCLUSIONS: Bioceramic-based sealer had less cytotoxicity and genotoxicity and similar antibacterial effect against E. faecalis in comparison with AH Plus sealer. PMID- 26281003 TI - Kinetics of Heterogeneous Reaction of Sulfur Dioxide on Authentic Mineral Dust: Effects of Relative Humidity and Hydrogen Peroxide. AB - Heterogeneous reaction of SO2 on mineral dust seems to be an important sink for SO2. However, kinetic data about this reaction on authentic mineral dust are scarce and are mainly limited to low relative humidity (RH) conditions. In addition, little is known about the role of hydrogen peroxide (H2O2) in this reaction. Here, we investigated the uptake kinetics of SO2 on three authentic mineral dusts (i.e., Asian mineral dust (AMD), Tengger desert dust (TDD), and Arizona test dust (ATD)) in the absence and presence of H2O2 at different RHs using a filter-based flow reactor, and applied a parameter (effectiveness factor) to the estimation of the effective surface area of particles for the calculation of the corrected uptake coefficient (gammac). We found that with increasing RH, the gammac decreases on AMD particles, but increases on ATD and TDD particles. This discrepancy is probably due to the different mineralogy compositions and aging extents of these dust samples. Furthermore, the presence of H2O2 can promote the uptake of SO2 on mineral dust at different RHs. The probable explanations are that H2O2 rapidly reacts with SO2 on mineral dust in the presence of adsorbed water, and OH radicals, which can be produced from the heterogeneous decomposition of H2O2 on the mineral dust, immediately react with adsorbed SO2 as well. Our results suggest that the removal of SO2 via the heterogeneous reaction on mineral dust is an important sink for SO2 and has the potential to alter the physicochemical properties (e.g., ice nucleation ability) of mineral dust particles in the atmosphere. PMID- 26281004 TI - Synthesis of oligo- and polysaccharides by Lactobacillus reuteri 121 reuteransucrase at high concentrations of sucrose. AB - GTFA, a glucansucrase enzyme of the probiotic bacterium Lactobacillus reuteri 121, is capable of synthesizing an alpha-glucan polysaccharide with (1 -> 4) and (1 -> 6) linkages from sucrose. With respect to its biosynthesis, the present study has shown that the ratio of oligosaccharide versus polysaccharide synthesized was directly proportional to the concentration of sucrose. It appears that the size distribution of products is kinetically controlled, but the linkage distribution in the polysaccharide material is not changed. At high sucrose concentrations the sucrose isomers leucrose and trehalulose were synthesized, using the accumulated fructose as acceptor, together with 4'- and 6'-alpha-D glucosyl-leucrose and 6'-alpha-D-glucosyl-trehalulose. The finding of an additional branched hexasaccharide demonstrates that the enzyme is able to introduce branch-points already in relatively short oligosaccharides. PMID- 26281005 TI - Synthesis of hierarchical NiCo2O4 hollow nanorods via sacrificial-template accelerate hydrolysis for electrochemical glucose oxidation. AB - Hierarchical NiCo2O4 hollow nanorods (HR) were directly grown on stainless steel via a sacrificial template accelerated hydrolysis and post calcination using ZnO nanorod as a template. The composition of the NiCo2O4 HR electrode was determined using X-ray diffraction and X-ray photoelectron spectroscopy. The morphology of the NiCo2O4 HR is comprised of nanoflakes that were characterized with scanning electron microscopy and transmission electron microscopy. The mixed-valence metal oxide and hollow structure provided high chemical reactivity and a large surface area for glucose oxidation in an alkaline solution. Under an optimal applied potential of +0.6 V, the developed NiCo2O4 HR electrode showed a broad detection range of 0.0003-1.0 mM, a sensitivity of 1685.1 MUA mM-1 cm-2, and a low detection limit of 0.16 MUM. These results represent a significant improvement over both NiO and Co3O4 HR. The developed NiCo2O4 HR electrode not only demonstrated excellent selectivity in the presence of several electro-active species, but also exhibited high stability following a 200 cycles voltammetry test. PMID- 26281006 TI - Controlling Solid-Gas Reactions at Nanoscale for Enhanced Thin Film Morphologies and Device Performances in Solution-Processed Cu2ZnSn(S,Se)4 Solar Cells. AB - Using Cu2ZnSn(S,Se)4 (CZTSSe) as a model system, we demonstrate the kinetic control of solid-gas reactions at nanoscale by manipulating the surface chemistry of both sol-gel nanoparticles (NPs) and colloidal nanocrystals (NCs). Specifically, we first identify that thiourea (commonly used as sulfur source in sol-gel processes for metal sulfides) can transform into melamine upon film formation, which serves as surface ligands for as-formed Cu2ZnSnS4 (CZTS) NPs. We further reveal that the presence of these surface ligands can significantly affect the outcome of the solid-gas reactions, which enables us to effectively control the selenization process during the fabrication of CZTSSe solar cells and achieve optimal film morphologies (continuous large grains) by fine-tuning the amount of surface ligands used. Such enhancement leads to better light absorption and allows us to achieve 6.5% efficiency from CZTSSe solar cells processed via a sol-gel process using nontoxic, low boiling point mixed solvents. We believe our discovery that the ligand of particulate precursors can significantly affect solid-gas reactions is universal to solid-state chemistry and will boost further research in both understanding the fundamentals of solid-state reactions at nanoscale and taking advantage of these reactions to fabricate crystalline thin film semiconductors with better morphologies and performances. PMID- 26281007 TI - Antihypertensive and neuroprotective actions of pyridoxine and its derivatives. AB - Vitamin B6 plays a crucial role in the nervous system as the amino acid decarboxylases involved in the synthesis of all putative neurotransmitters requires the coenzyme pyridoxal phosphate. Vitamin B6 in its various forms has antioxidant properties. Pyridoxal phosphate has a role in regulating cellular calcium transport through both the voltage-mediated and ATP-mediated purinergic mechanisms of cellular calcium influx and, hence, has a role in the control of hypertension. Pharmacological doses of vitamin B6 appear to decrease the high blood pressure associated with both genetic and nongenetic models of hypertension. Vitamin B6 has a crucial role in the normal function of the central and peripheral nervous systems. It also protects against ischemia and glutamate induced neurotoxicity. PMID- 26281008 TI - Amelioration of Osteoporosis and Hypovitaminosis D by Sunlight Exposure in Hospitalized Elderly Women With Alzheimer's Disease: A Randomized Controlled Trial. PMID- 26281010 TI - Impact of Question Content on e-Consultation Outcomes. AB - BACKGROUND: By facilitating direct communication of primary care providers (PCPs) with specialists for advice, electronic consult (e-consult) services can reduce the need for patients to wait for and travel to face-to-face consultations with specialists. An association between avoiding face-to-face referrals using an e consult service and specific content within each e-consult has not been rigorously explored. MATERIALS AND METHODS: Cases submitted to the Champlain Building Access to Specialists through eConsultation service between April 2011 to May 2013 were evaluated. Factors analyzed include question type (e.g., diagnosis or management), formulation (if interventions or outcomes were specified), and the addressed specialty. An avoided referral was present if the PCP indicated so in a mandatory close-out survey. A discrepancy was present if the PCP made a referral when the specialist did not indicate one was necessary, or if the PCP did not request a referral despite the specialist recommending one. RESULTS: There were 426 (40%) avoided referrals among 1,055 cases analyzed. Questions associated with the highest avoided referral rates included ones pertaining to diagnosis (44%), nonspecific requests for direction (44%), questions without specified interventions or outcomes (47%), and dermatology cases (49.5%). Specialists agreed on the need for a referral in 82% of cases, with most discrepancies due to the PCP making a referral without the specialist recommending one. CONCLUSIONS: Referral outcomes are associated with the type of question being asked, the formulation of each question, and the specialty being addressed. Discrepancies among PCPs and specialists regarding which patients require face-to-face referrals may help identify knowledge gaps and guide professional development. PMID- 26281011 TI - Cyclophilin polymorphism and virus infection. AB - Viruses are obligate intracellular parasites. All stages of their replication cycle depend on support by host-encoded factors. However, sequence variation also exists in host factors mostly in the form of single nucleotide polymorphisms (SNPs). Several coding and non-coding genetic variants in the PPIA gene encoding for CypA have been described, but there is only limited information about their influence on the course of viral infection. This paper reviews PPIA polymorphisms and what is known about their impact on the replication cycle and course of disease for different viral infections. PMID- 26281012 TI - Development and validation of an epidermolysis bullosa family/parental burden score. AB - BACKGROUND: The notion of the individual burden associated with a disease has been introduced to determine 'disability' in the broadest sense: psychological, social, economic and physical. Subtypes of epidermolysis bullosa (EB) are rare, life-threatening, untreatable chronic genodermatoses. OBJECTIVES: To develop and validate a specific questionnaire assessing the burden on families of children with EB: Epidermolysis Bullosa Burden of Disease (EB-BoD). METHODS: Items were generated by a verbatim report from parents of children with EB. Subsequently, a study was implemented for psychometric analysis. An epidermolysis bullosa burden of-disease questionnaire was refined via item reduction according to inter question correlations, consensus among experts and exploratory factor analysis. Internal consistency was determined by calculating Cronbach's alpha. Concurrent validity was determined by calculating the correlation between EB-BoD and the Short-Form 12 items (SF-12) questionnaire. RESULTS: From a primary list of 30 items, EB-BoD was reduced to a 20-item questionnaire, covering four disease aspects based on the exploratory factor analysis. Construct validity was demonstrated and the EB-BoD questionnaire showed good internal consistency (Cronbach's alpha = 0.9). The resulting EB-BoD score was significantly correlated to the mental dimension of SF-12 (r = -0.61), but it was not correlated to it's physical dimension (r = 0.04). EB-BoD scores were significantly discriminating between EB subtypes. CONCLUSIONS: The EB-BoD questionnaire appears to be a useful assessment tool regarding medical and socioeconomic issues in patients with EB and their families. EB-BoD scores correlate well with the family/parental burden experienced by the families of patients with EB. PMID- 26281013 TI - Maternal Determinants of Birth Weight in Northern Ghana. AB - OBJECTIVES: Weight at birth is usually considered as an indicator of the health status of a given society. As a result this study was designed to investigate the association between birth weight and maternal factors such as gestational weight gain, pre-pregnancy BMI and socio-economic status in Northern Ghana. METHODS: The study was a facility-based cross-sectional survey conducted in two districts in the Northern region of Ghana. These districts were purposively sampled to represent a mix of urban, peri-urban and rural population. The current study included 419 mother-infant pairs who delivered at term (37-42 weeks). Mother's height, pre-pregnancy weight and weight changes were generated from the antenatal records. Questionnaires were administered to establish socio-economic and demographic information of respondents. Maternal factors associated with birth weight were examined using multiple and univariate regressions. RESULTS: The mothers were generally well nourished before conception (Underweight 3.82%, Normal 57.76%, Overweight 25.06% and Obesity 13.37%) but approximately half of them could not gain adequate weight according to Institute of Medicine recommendations (Low weight gain 49.64%, Adequate weight gain 42.96% and Excessive weight gain 7.40%). Infants whose mothers had excess weight gain were 431g (95% CI 18-444) heavier compared to those whose mothers gained normal weight, while those whose mothers gained less were 479g (95% CI -682- (-276) lighter. Infants of mothers who were overweight and obese before conception were 246g (95% CI 87-405) and 595g (95% CI 375-815) respectively heavier than those of normal mothers, whereas those whose mothers were underweight were 305g (95% CI 565 -(-44) lighter. The mean birth weight observed was 2.98 +/- 0.68 kg. CONCLUSION: Our findings show that pre-pregnancy body mass index and weight gain during pregnancy influence birth weight. Therefore, emphasis should be placed on counseling and assisting pregnant women to stay within the recommended weight gain ranges. PMID- 26281014 TI - Contrasting Strategies of Alfalfa Stem Elongation in Response to Fall Dormancy in Early Growth Stage: The Tradeoff between Internode Length and Internode Number. AB - Fall dormancy (FD) in alfalfa (Medicago sativa L.) can be described using 11 FD ratings, is widely used as an important indicator of stress resistance, productive performance and spring growth. However, the contrasting growth strategies in internode length and internode number in alfalfa cultivars with different FD rating are poorly understood. Here, a growth chamber study was conducted to investigate the effect of FD on plant height, aboveground biomass, internode length, and internode number in alfalfa individuals in the early growth stages. In order to simulate the alfalfa growth environment in the early stage, 11 alfalfa cultivars with FD ratings from one to 11 were chosen and seeded at the greenhouse, and then were transplanted into an artificial growth chamber. The experimental design was a randomized complete block in a split-plot arrangement with three replicates. Plant height, above-ground biomass, internode length, and internode number were measured in early growth stage in all individuals. Our findings showed that plant height and the aboveground biomass of alfalfa did not significantly differ among 11 different FD rated cultivars. Also, internode length and internode number positively affected plant height and the aboveground biomass of alfalfa individuals and the average internode length significantly increased with increasing FD rating. However, internode number tended to sharply decline when the FD rating increased. Moreover, there were no correlations, slightly negative correlations, and strongly negative correlations between internode length and internode number in alfalfa individuals among the three scales, including within-FD ratings, within-FD categories and inter-FD ratings, respectively. Therefore, our results highlighted that contrasting growth strategies in stem elongation were adopted by alfalfa with different FD ratings in the early growth stage. Alfalfa cultivars with a high FD rating have longer internodes, whereas more dormant alfalfa cultivars have a larger number of internodes. There were tradeoffs between internode length and internode number in response to FD in alfalfa, which reflected certain scale-dependence. PMID- 26281016 TI - Influence of Chemical Composition and Structure in Silicon Dielectric Materials on Passivation of Thin Crystalline Silicon on Glass. AB - In this study, various silicon dielectric films, namely, a-SiOx:H, a-SiNx:H, and a-SiOxNy:H, grown by plasma enhanced chemical vapor deposition (PECVD) were evaluated for use as interlayers (ILs) between crystalline silicon and glass. Chemical bonding analysis using Fourier transform infrared spectroscopy showed that high values of oxidant gases (CO2 and/or N2), added to SiH4 during PECVD, reduced the Si-H and N-H bond density in the silicon dielectrics. Various three layer stacks combining the silicon dielectric materials were designed to minimize optical losses between silicon and glass in rear side contacted heterojunction pn test cells. The PECVD grown silicon dielectrics retained their functionality despite being subjected to harsh subsequent processing such as crystallization of the silicon at 1414 degrees C or above. High values of short circuit current density (Jsc; without additional hydrogen passivation) required a high density of Si-H bonds and for the nitrogen containing films, additionally, a high N-H bond density. Concurrently high values of both Jsc and open circuit voltage Voc were only observed when [Si-H] was equal to or exceeded [N-H]. Generally, Voc correlated with a high density of [Si-H] bonds in the silicon dielectric; otherwise, additional hydrogen passivation using an active plasma process was required. The highest Voc ~ 560 mV, for a silicon acceptor concentration of about 10(16) cm(-3), was observed for stacks where an a-SiOxNy:H film was adjacent to the silicon. Regardless of the cell absorber thickness, field effect passivation of the buried silicon surface by the silicon dielectric was mandatory for efficient collection of carriers generated from short wavelength light (in the vicinity of the glass-Si interface). However, additional hydrogen passivation was obligatory for an increased diffusion length of the photogenerated carriers and thus Jsc in solar cells with thicker absorbers. PMID- 26281015 TI - Generation of iPSCs as a Pooled Culture Using Magnetic Activated Cell Sorting of Newly Reprogrammed Cells. AB - Although significant advancement has been made in the induced pluripotent stem cell (iPSC) field, current methods for iPSC derivation are labor intensive and costly. These methods involve manual selection, expansion, and characterization of multiple clones for each reprogrammed cell sample and therefore significantly hampers the feasibility of studies where a large number of iPSCs need to be derived. To develop higher throughput iPSC reprogramming methods, we generated iPSCs as a pooled culture using rigorous cell surface pluripotent marker selection with TRA-1-60 or SSEA4 antibodies followed by Magnetic Activated Cell Sorting (MACS). We observed that pool-selected cells are similar or identical to clonally derived iPSC lines from the same donor by all criteria examined, including stable expression of endogenous pluripotency genes, normal karyotype, loss of exogenous reprogramming factors, and in vitro spontaneous and lineage directed differentiation potential. This strategy can be generalized for iPSC generation using both integrating and non-integrating reprogramming methods. Our studies provide an attractive alternative to clonal derivation of iPSCs using rigorously selected cell pools and is amenable to automation. PMID- 26281017 TI - Advanced Glycation End Products Modulate Structure and Drug Binding Properties of Albumin. AB - The extraordinary ligand binding properties of albumin makes it a key player in the pharmacokinetics and pharmacodynamics of many vital drugs. Albumin is highly susceptible for nonenzymatic glycation mediated structural modifications, and there is a need to determine structural and functional impact of specific AGEs modifications. The present study was aimed toward determining the AGE mediated structure and function changes, primarily looking into the effect on binding affinity of drugs in the two major drug binding sites of albumin. The impact of the two most predominant AGEs modifications, i.e., carboxyethyllysine (CEL) and argpyrimidine (Arg-P), was studied on the basis of the combination of in vitro and in silico experiments. In vitro studies were carried out by AGEs modification of bovine serum albumin (BSA) for the formation of Arg-P and CEL followed by drug interaction studies. In silico studies involved molecular dynamics (MD) simulations and docking studies for native and AGEs modified BSAs. In particular the side chain modification was specifically carried out for the residues in the drug binding sites, i.e., Arg-194, Arg-196, Arg-198, and Arg-217, and Lys-204 (site I) and Arg-409 and Lys-413 (site II). The equilibrated structures of native BSA (n-BSA) and glycated BSA (G-BSA) as obtained from MD were used for drug binding studies using molecular docking approach. It was evident from the results of both in vitro and in silico drug interaction studies that AGEs modification results in the reduced drug binding affinity for tolbutamide (TLB) and ibuprofen (IBP) in sites I and II. Moreover, the AGEs modification mediated conformational changes resulted in the shallow binding pockets with reduced accessibility for drugs. PMID- 26281018 TI - The efficacy of short-term psychodynamic psychotherapy for depression: A meta analysis update. AB - OBJECTIVES: The efficacy of short-term psychodynamic psychotherapy (STPP) for depression is debated. Recently, a number of large-scale and high-quality studies have been conducted. We examined the efficacy of STPP by updating our 2010 meta analysis. RESULTS: After a thorough literature search, 54 studies (33 randomized clinical trials) totaling 3946 subjects were included. STPP was significantly more effective than control conditions at post-treatment on depression, general psychopathology and quality of life measures (d=0.49 to 0.69). STPP pre-treatment to post-treatment changes (d=0.57 to 1.18) indicated significant improvements on all outcome measures, which either significantly improved further (d=0.20 to 1.04) or were maintained from post-treatment to follow-up. No significant differences were found between individual STPP and other psychotherapies at post treatment (d=-0.14) and follow-up (d=-0.06) in analyses that were adequately powered to detect a clinically relevant difference. STPP was significantly more efficacious than other psychotherapies on anxiety measures at both post-treatment (d=0.35) and follow-up (d=0.76). CONCLUSION: We found clear indications that STPP is effective in the treatment of depression in adults. Although more high-quality studies are needed, particularly to assess the efficacy of STPP compared to control conditions at follow-up and to antidepressants, these findings add to the evidence-base of STPP for depression. PMID- 26281019 TI - Reactions of Azine Anions with Nitrogen and Oxygen Atoms: Implications for Titan's Upper Atmosphere and Interstellar Chemistry. AB - Azines are important in many extraterrestrial environments, from the atmosphere of Titan to the interstellar medium. They have been implicated as possible carriers of the diffuse interstellar bands in astronomy, indicating their persistence in interstellar space. Most importantly, they constitute the basic building blocks of DNA and RNA, so their chemical reactivity in these environments has significant astrobiological implications. In addition, N and O atoms are widely observed in the ISM and in the ionospheres of planets and moons. However, the chemical reactions of molecular anions with abundant interstellar and atmospheric atomic species are largely unexplored. In this paper, gas-phase reactions of deprotonated anions of benzene, pyridine, pyridazine, pyrimidine, pyrazine, and s-triazine with N and O atoms are studied both experimentally and computationally. In all cases, the major reaction channel is associative electron detachment; these reactions are particularly important since they control the balance between negative ions and free electron densities. The reactions of the azine anions with N atoms exhibit larger rate constants than reactions of corresponding chain anions. The reactions of azine anions with O atoms are even more rapid, with complex product patterns for different reactants. The mechanisms are studied theoretically by employing density functional theory; spin conversion is found to be important in determining some product distributions. The rich gas phase chemistry observed in this work provides a better understanding of ion-atom reactions and their contributions to ionospheric chemistry as well as the chemical processing that occurs in the boundary layers between diffuse and dense interstellar clouds. PMID- 26281021 TI - Guest Editorial: 'The voice of the child in oral health research'. PMID- 26281020 TI - Analysis of cytotoxic effects of silver nanoclusters on human peripheral blood mononuclear cells 'in vitro'. AB - The antimicrobial properties of silver nanoparticles (AgNPs) have made these particles one of the most used nanomaterials in consumer products. Therefore, an understanding of the interactions (unwanted toxicity) between nanoparticles and human cells is of significant interest. The aim of this study was to assess the in vitro cytotoxicity effects of silver nanoclusters (AgNC, < 2 nm diameter) on peripheral blood mononuclear cells (PBMC). Using flow cytometry and comet assay methods, we demonstrate that exposure of PBMC to AgNC induced intracellular reactive oxygen species (ROS) generation, DNA damage and apoptosis at 3, 6 and 12 h, with a dose-dependent response (0.1, 1, 3, 5 and 30 ug ml(-1)). Advanced electron microscopy imaging of complete and ultrathin-sections of PBMC confirmed the cytotoxic effects and cell damage caused by AgNC. The present study showed that AgNC produced without coating agents induced significant cytotoxic effects on PBMC owing to their high aspect ratio and active surface area, even at much lower concentrations (<1 ug ml(-1)) than those applied in previous studies, resembling what would occur under real exposure conditions to nanosilver functionalized consumer products. PMID- 26281022 TI - Socioeconomic inequalities in prostate cancer survival: A review of the evidence and explanatory factors. AB - Although survival rates after prostate cancer diagnosis have improved in the past two decades, survival analyses regarding the socioeconomic status (SES) suggest inequalities indicating worse prognosis for lower SES groups. An overview of the current literature is lacking and moreover, there is an ongoing discussion about the underlying causes but evidence is comparatively sparse. Several patient, disease and health care related factors are discussed to have an important impact on disparities in survival. Therefore, a systematic review was conducted to sum up the current evidence of survival inequalities and the contribution of different potential explanatory factors among prostate cancer patients. The PubMed database was screened for relevant articles published between January 2005 and September 2014 revealing 330 potentially eligible publications. After systematic review process, 46 papers met the inclusion criteria and were included in the review. About 75% of the studies indicate a significant association between low SES and worse survival among prostate cancer patients in the fully adjusted model. Overall, hazard ratios (low versus high SES) range from 1.02 to 3.57. A decrease of inequalities over the years was not identified. 8 studies examined the impact of explanatory factors on the association between SES and survival by progressive adjustment indicating mediating effects of comorbidity, stage at diagnosis and treatment modalities. Eventually, an apparent majority of the obtained studies indicates lower survival among patients with lower SES. The few studies that intend to explain inequalities found out instructive results regarding different contributing factors but evidence is still insufficient. PMID- 26281023 TI - Epidemiology of Traumatic Brain Injury After Small-Wheeled Vehicle Trauma in Utah. AB - BACKGROUND: Recreational use of small-wheeled vehicles (SWVs), which include skateboards, longboards, nonmotorized scooters, ice skates, and roller skates or rollerblades, results in numerous injuries in the United States. OBJECTIVE: To describe the nature and severity of traumatic brain injuries (TBIs) that result from the use of SWVs in Utah. METHODS: Patients who were admitted to any Utah hospital after a SWV-related injury from 2001 through 2010 were identified from the Utah State Trauma Registry. Patients who sustained TBI were identified by International Classification of Diseases, Ninth Revision, codes. RESULTS: Of 907 patients admitted with SWV injury, 392 (43%) had a TBI (85% male). Their mean age was 19.8 +/- 0.5 years, including 234 (60%) aged <=18 and 119 (30%) aged 19 to 29. Most patients sustained TBI while using a skate- or longboard (87%). Mean Glasgow Coma Scale score in the emergency department was 12.8 +/- 0.2. Thirty nine percent were admitted to an intensive care unit, and 6% (23) underwent emergent neurosurgical intervention. Thirty-three (8.4%) patients had a concussion; the rest had nonoperative intracranial hemorrhage. Among patients for whom helmet use data were available, 8 out of 291 (2.7%) patients with TBI were wearing a helmet, whereas 24 out of 190 (12.6%) non-TBI patients were wearing helmets (P < .001). Overall mortality was higher in TBI patients than in non-TBI patients (2.3% vs 0.2%, P = .003). CONCLUSION: Young people, especially males, who ride SWVs in Utah are at risk for serious TBI, admission to the intensive care unit, neurosurgical intervention, and death. Helmet use in these patients is likely rare, but may reduce the risk of TBI and death. ABBREVIATIONS: ED, emergency departmentSWV, small-wheeled vehicleTBI, traumatic brain injury. PMID- 26281025 TI - In Reply: Different Facets in Management of Congenital Atlantoaxial Dislocation and Basilar Invagination. PMID- 26281026 TI - Walter Dandy (1886-1946): A Personal Retrospective. PMID- 26281027 TI - Airborne Thermal Remote Sensing for Estimation of Groundwater Discharge to a River. AB - Traditional methods for studying surface water and groundwater interactions have usually been limited to point measurements, such as geochemical sampling and seepage measurement. A new methodology is presented for quantifying groundwater discharge to a river, by using river surface temperature data obtained from airborne thermal infrared remote sensing technology. The Hot Spot Analysis toolkit in ArcGIS was used to calculate the percentage of groundwater discharge to a river relative to the total flow of the river. This methodology was evaluated in the midstream of the Heihe River in the arid and semiarid northwest China. The results show that the percentage of groundwater discharge relative to the total streamflow was as high as 28%, which is in good agreement with the results from previous geochemical studies. The data analysis methodology used in this study is based on the assumption that the river water is fully mixed except in the areas of extremely low flow velocity, which could lead to underestimation of the amount of groundwater discharge. Despite this limitation, this remote sensing-based approach provides an efficient means of quantifying the surface water and groundwater interactions on a regional scale. PMID- 26281028 TI - Systematic review of acupuncture to control hot flashes in cancer patients. AB - Hot flashes (HFs) are a common side effect of cancer treatment. The purpose of this systematic review was to evaluate evidence related to the use of acupuncture for HFs in cancer patients. EMBASE, MEDLINE, Cochrane (all databases), PubMed, the Cumulative Index to Nursing and Allied Health Literature, and Scopus were searched from their inception through December 2014. Included studies had to be randomized controlled trials with a usual-care and/or placebo comparison group that investigated acupuncture to treat HFs in cancer patients. No language limits were applied. The risk of bias (ROB) was rated as low, high, or unclear according to Cochrane criteria. Both within-group and between-group changes were evaluated. Four hundred two items were identified, and 192 duplicates were omitted; this left 210 publications to be screened. Eight studies met the inclusion criteria, and all involved women with breast cancer. All studies showed significant within group improvement from the baseline for true acupuncture (TA). One study showed significant improvement in favor of TA over sham acupuncture (SA; P < .001), 1 study found in favor of TA over SA for nighttime HFs only (P = .03), and 1 study found in favor of TA over SA or untreated controls (P < .01 and P < .001, respectively). Between-group (TA vs SA) effect size (ES) estimates for daytime and nighttime HFs were calculated (ES range, 0.04-0.9) whenever possible. No studies were rated with a low ROB. In conclusion, the current level of evidence is insufficient to either support or refute the benefits of acupuncture for the management of HFs in cancer patients. Future studies should provide within-group and between-group ES estimates in addition to P values. PMID- 26281029 TI - Safety and feasibility of romiplostim treatment for patients with persistent thrombocytopenia after allogeneic stem cell transplantation. PMID- 26281030 TI - Impact of novel agents followed by autologous hematopoietic stem cell transplantation for multiple myeloma patients aged 65 years or older: a retrospective single Institutional analysis. PMID- 26281031 TI - Autologous stem cell transplantation for adult acute leukemia in 2015: time to rethink? Present status and future prospects. AB - The use of autologous stem cell transplantation (ASCT) as consolidation therapy for adult patients with acute leukemia has declined over time. However, multiple randomized studies in the past have reported lower relapse rates after autologous transplantation compared with chemotherapy and lower non-relapse mortality rates compared with allogeneic transplantation. In addition, quality of life of long term survivors is better after autologous transplantation than after allogeneic transplantation. Further, recent developments may improve outcomes of autograft recipients. These include the use of IV busulfan and the busulfan+melphalan combination, better detection of minimal residual disease (MRD) with molecular biology techniques, the introduction of targeted therapies and post-transplant maintenance therapy. Therefore, ASCT may nowadays be reconsidered for consolidation in the following patients if and when they reach a MRD-negative status: good- and at least intermediate-1 risk acute myelocytic leukemia in first CR, acute promyelocytic leukemia in second CR, Ph-positive acute lymphocytic leukemia. Conversely, patients with MRD-positive status or high-risk leukemia should not be considered for consolidation with ASCT. PMID- 26281032 TI - Incidence and risk factors of post-engraftment invasive fungal disease in adult allogeneic hematopoietic stem cell transplant recipients receiving oral azoles prophylaxis. AB - Studies that analyze the epidemiology and risk factors for invasive fungal disease (IFD) after engraftment in alloSCT are few in number. This single-center retrospective study included 404 alloSCT adult recipients surviving >40 days who engrafted and were discharged without prior IFD. All patients who received ?20 mg/day of prednisone were assigned to primary oral prophylaxis (itraconazole or low-dose voriconazole). The primary end point was the cumulative incidence (CI) of probable/proven IFD using the European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG) criteria. The independent prognostic factors after multivariate analyses were used to construct a post engraftment IFD risk score. The 1-year CI of IFD was 11%. The non-relapse mortality was 40% in those developing IFD and 16% in those who did not. The intent-to-treat analysis showed that 17% of patients abandoned the assigned prophylaxis. Age >40 years, ?1 previous SCT, pre-engraftment neutropenia >15 days, extensive chronic GVHD and CMV reactivation were independent risk factors. The post-engraftment IFD score stratified patients into low risk (0-1 factor, CI 0.7%), intermediate risk (2 factors, CI 9.9%) and high risk (3-5 factors, CI 24.7%) (P<0.0001). The antifungal prophylaxis strategy failed to prevent post engraftment IFD in 11% of alloSCT. Our risk score could be useful to implement risk-adapted strategies using antifungal prophylaxis after engraftment. PMID- 26281034 TI - A simple stochastic model for the feedback circuit between p16INK4a and p53 mediated by p38MAPK: implications for senescence and apoptosis. AB - The mechanisms leading to the cell fate decision between apoptosis and senescence upon DNA damage are still unclear and have stochastic features. Cellular oxidative stress can generate DNA damage and activate the important mitogen activated protein kinase 14 (p38MAPK) that is involved in pathologies like Alzheimer's disease. Based on experimental evidence we propose a simple network that might operate at the core of the cell control machinery for the choice between apoptosis and senescence involving the cross-talk between p38MAPK, the tumor suppressor protein p53 and the cyclin-dependent kinase inhibitor (p16INK4a). We have performed two types of analyses, deterministic and stochastic, exploring the system's parameter space, in the first, we calculated the fixed points of the deterministic model and, in the second, we numerically integrated the master equation for the stochastic version. The model shows a variety of behaviors dependent on the parameters including states of high expression levels of p53 or p16INK4a that can be associated with an apoptotic or senescent phenotype, respectively, in agreement with experimental data. In addition, we observe both monostable and bistable behavior (where bistability is a phenomenon in which two stable steady states coexist for a fixed set of control parameter values) which here we suggest to be involved in the cell fate decision problem. PMID- 26281035 TI - Advances in mechanical assist devices and artificial hearts for children. AB - PURPOSE OF REVIEW: Mechanical circulatory support (MCS) has rapidly evolved toward continuous flow technology in adults. In the pediatric population, the Berlin EXCOR, a paracorporeal pulsatile pump, is the only MCS device specifically approved for pediatric use. The current era of pediatric MCS includes an increasing application of adult continuous flow pumps to pediatric patients. RECENT FINDINGS: The Berlin EXCOR pulsatile pump has been studied in over 200 patients. The major limitations of this device are neurologic dysfunction (which occurs in about 30% of supported patients) and the requirement for in-hospital care until transplant. Two continuous flow pumps (HVAD and HeartMate II) have been successfully applied in children and adolescents, and the SynCardia total artificial heart has been used in adolescents. The National Heart, Lung, and Blood Institute - sponsored Pediatric Mechanically Assisted Circulatory Support registry has collected pediatric MCS data since 2012 and will provide valuable outcomes data to help refine this field. Survival with these durable devices has been generally good (except for small infants and patients with complex congenital heart disease), with nearly 50% receiving a heart transplant within 6 months. Patients with single ventricle physiology continue to pose major challenges. Two clinical trials for miniaturized adult continuous flow devices and one trial for a new pediatric pump will begin within the next year. SUMMARY: New continuous flow devices are entering or poised to enter clinical trials. If approved, these devices will enhance the safety and variety of options for longer term pediatric support. PMID- 26281033 TI - Post-autologous transplant maintenance therapies in lymphoid malignancies: are we there yet? AB - Disease relapse after autologous hematopoietic transplant (auto-HCT) remains the number one cause of post-transplant therapy failure and mortality. The last decade has seen a proliferation of clinical studies looking at the prevention of post-auto-HCT therapy failure with various maintenance strategies. The benefit of such therapies is in turn dependent on disease histology and timing of transplantation. Although high dose therapy (HDT) provides durable responses in chemosensitive relapsed diffuse large B-cell lymphoma (DLBCL), a sizable subset experiences disease relapse. Unfortunately, the addition of rituximab as a post auto-HCT maintenance strategy did not improve survival outcomes. The preliminary results with programmed death -1 (PD-1) Ab as post-auto maintenance in DLBCL is promising but requires randomized validation. In follicular lymphoma, the 5- and 10-year PFS rates are ~60% and 31%, respectively. Although the addition of rituximab improved PFS, there is no survival benefit, to date. Disease relapse after auto-HCT in mantle cell lymphoma (MCL) is not uncommon. Rituximab maintenance in this setting provides a PFS benefit. Given the poor prognosis of post-auto-HCT failures in MCL, maintenance can be considered on a case-by-case basis. In chemosensitive relapsed Hodgkin lymphoma, addition of brentuximab vedotin after auto-HCT improved 2-year PFS (65 vs 45%) and can be considered as an option for maintenance therapy post auto-HCT, in select higher risk patients. Ongoing trials evaluating the efficacy of post-auto-HCT maintenance with novel agents (for example, immunomodulators, proteasome inhibitors, PD-1 inhibitors, Bruton's tyrosine kinase inhibitors and so on) will likely change the practice landscape for lymphoma patients following HDT and auto-HCT. PMID- 26281036 TI - The Fontan operation: the long-term outlook. AB - PURPOSE OF REVIEW: As perioperative survival following the Fontan procedure has improved and more patients are reaping the benefits of physiologic palliation, the costs of longstanding systemic venous hypertension and the functional limitations of a single ventricle are becoming clearer. Arrhythmias, heart failure, protein-losing enteropathy, hepatic cirrhosis, pulmonary hypertension, and ventricular dysfunction are common in late survivors and result in significant morbidity and mortality. Current research is focused on characterizing late morbidities and developing risk-prediction models for worse outcomes in long-term survivors. RECENT FINDINGS: Ten-year survival following the Fontan procedure is now 94-98%; however, estimated conditional survival in survivors aged above 18 years is 60% at 40 years of age. Atrial arrhythmias and heart failure are the leading causes of morbidity and mortality. Hypoplastic left heart syndrome, hepatic dysfunction, decreased exercise tolerance, lower quality of life, and markers of neurohormonal activation have been associated with worse outcome. Improvements in exercise tolerance are seen with selective pulmonary vasodilator therapy and exercise training. Heart transplant continues to be an effective therapy for end-stage Fontan failure, and reports of the use of traditional mechanical assist devices and the development of right heart assist devices in the setting of passive venous flow are ongoing. SUMMARY: Over a generation has passed since the Fontan procedure revolutionized the care of patients with a single ventricle. Data generated from retrospective and prospective observational studies in long-term survivors are identifying patients at risk. PMID- 26281037 TI - Long-term challenges in congenital heart disease. PMID- 26281038 TI - Barriers and facilitators of mental health screening in pregnancy. AB - BACKGROUND: Access to mental health services during pregnancy is most commonly mobilized through formal mental health screening. However, few studies to date have identified barriers and facilitators that affect pregnant women's responses to mental health screening. The objective was to identify barriers and facilitators that influence pregnant women's responses to the screening process and factors associated with their identification. METHODS: This multi-site, cross sectional survey recruited pregnant women >16 years of age who spoke/read English in Alberta, Canada. Main outcomes were barriers and facilitators of mental health screening. Descriptive statistics were generated to identify the most common barriers and facilitators and multivariable logistic regression models were conducted to determine factors associated with barriers and facilitators. RESULTS: Study participation rate was 92% (460/500). Women's most common barriers were: significant others normalizing their emotional difficulties; desiring to handle mental health problems on their own; preferring to discuss feelings with significant others; and not knowing what emotions were 'normal'. Women who identified these barriers were more likely not to have been treated previously for mental illness, were primiparous, and could not be completely honest with their provider. Main facilitators were provider characteristics (sensitive, interested), reassurance that mental healthcare is a part of routine prenatal care, hearing that other women have emotional problems during pregnancy and knowing that help was available. LIMITATIONS: The sample comprised largely Caucasian, well-educated, and partnered women, which limits generalizability of the findings. CONCLUSIONS: Personal and stigma-related barriers influence pregnant women's responses to mental health screening. Efforts to minimize barriers and enhance facilitators should be explored as potential strategies for optimizing prenatal mental health screening. PMID- 26281039 TI - The serotonin transporter in depression: Meta-analysis of in vivo and post mortem findings and implications for understanding and treating depression. AB - BACKGROUND: Altered serotonin transporter levels have been reported in blood and brain of patients with major depressive disorders. However, the strength and consistency of the evidence for altered serotonin transporter availability in major depressive disorder is not clear. METHODS: To address this, a comprehensive meta-analysis was conducted of all available in vivo neuroimaging and post mortem studies reporting serotonin transporter availability in patients with depression compared with healthy controls. RESULTS: The final sample consisted of fifty (n=27 in vivo and n=25 post mortem) studies including 877 patients with depression (mean age: 42.9 years) and 968 healthy controls (mean age: 42.7 years). In vivo neuroimaging studies indicated reduced serotonin transporter binding in the striatum (g=-0.39, p=0.01), the amygdala (g=-0.37, p=0.01) and the brainstem (g=-0.31, p=0.01), including the midbrain (g=-0.27, p=0.02), but no significant alteration in the thalamus or the hippocampus. The post mortem findings indicated no significant change in serotonin transporter binding in depression in the brainstem (p=0.64), the frontal cortex (p=0.75) and the hippocampus (p=0.32, corrected for publication bias). Although there were too few studies for a meta-analysis, the post mortem studies in the amygdala and striatum showed reduced SERT binding in MDD in absolute terms, consistent with the imaging findings. LIMITATIONS: A number of potential factors might have biased the results of the present meta-analysis such as the imaging modality (post mortem or in vivo neuroimaging), partial volume effects, susceptibility of some radiotracers to synaptic serotonin levels or binding to other monoamine transporters. CONCLUSIONS: The results indicate that serotonin transporter availability in depressed patients is reduced in key regions of the limbic system. This provides direct support for the serotonin hypothesis of depression, and underlines the importance of the serotonin transporter as a target of pharmacological treatments. PMID- 26281040 TI - Value of the P Value. PMID- 26281042 TI - Effects of Edge Directions on the Structural Controllability of Complex Networks. AB - Recent advances indicate that assigning or reversing edge direction can significantly improve the structural controllability of complex networks. For directed networks, approaching the optimal structural controllability can be achieved by detecting and reversing certain "inappropriate" edge directions. However, the existence of multiple sets of "inappropriate" edge directions suggests that different edges have different effects on optimal controllability that is, different combinations of edges can be reversed to achieve the same structural controllability. Therefore, we classify edges into three categories based on their direction: critical, redundant and intermittent. We then investigate the effects of changing these edge directions on network controllability, and demonstrate that the existence of more critical edge directions implies not only a lower cost of modifying inappropriate edges but also better controllability. Motivated by this finding, we present a simple edge orientation method aimed at producing more critical edge directions-utilizing only local information-which achieves near optimal controllability. Furthermore, we explore the effects of edge direction on the controllability of several real networks. PMID- 26281045 TI - Outbreak news. Chikungunya, Spain. PMID- 26281044 TI - Development of the Tardivo Algorithm to Predict Amputation Risk of Diabetic Foot. AB - Diabetes is a chronic disease that affects almost 19% of the elderly population in Brazil and similar percentages around the world. Amputation of lower limbs in diabetic patients who present foot complications is a common occurrence with a significant reduction of life quality, and heavy costs on the health system. Unfortunately, there is no easy protocol to define the conditions that should be considered to proceed to amputation. The main objective of the present study is to create a simple prognostic score to evaluate the diabetic foot, which is called Tardivo Algorithm. Calculation of the score is based on three main factors: Wagner classification, signs of peripheral arterial disease (PAD), which is evaluated by using Peripheral Arterial Disease Classification, and the location of ulcers. The final score is obtained by multiplying the value of the individual factors. Patients with good peripheral vascularization received a value of 1, while clinical signs of ischemia received a value of 2 (PAD 2). Ulcer location was defined as forefoot, midfoot and hind foot. The conservative treatment used in patients with scores below 12 was based on a recently developed Photodynamic Therapy (PDT) protocol. 85.5% of these patients presented a good outcome and avoided amputation. The results showed that scores 12 or higher represented a significantly higher probability of amputation (Odds ratio and logistic regression-IC 95%, 12.2-1886.5). The Tardivo algorithm is a simple prognostic score for the diabetic foot, easily accessible by physicians. It helps to determine the amputation risk and the best treatment, whether it is conservative or surgical management. PMID- 26281046 TI - Chikungunya: case definitions for acute, atypical and chronic cases. Conclusions of an expert consultation, Managua, Nicaragua, 20-21 May 2015. PMID- 26281043 TI - Evaluation of Stability and Biological Activity of Solid Nanodispersion of Lambda Cyhalothrin. AB - Pesticides are essential agrochemicals used to protect plants from diseases, pests and weeds. However, the formulation defects of conventional pesticides cause food toxicity and ecological environmental problems. In this study, a novel, efficient and environmentally friendly formulation of lambda-cyhalothrin, a solid nanodispersion, was successfully developed based on melt-emulsification and high-speed shearing methods. The solid nanodispersion presented excellent advantages over conventional pesticide formulations in such formulation functions as dispersibility, stability and bioavailability. The formulation is free of organic solvents, and the use of surfactant is reduced. Therefore, the application of the solid nanodispersion in crop production will improve efficacy and reduce the occurrence of both pesticide residues in food and environmental pollution from pesticides. PMID- 26281047 TI - WHO Global Influenza Surveillance and Response System working group on surveillance of influenza antiviral susceptibility. PMID- 26281048 TI - [Chronic rhinosinusitis and osteitis]. PMID- 26281049 TI - [Sublingual immunotherapy of allergic rhinitis]. PMID- 26281050 TI - [Discussion on single nucletide polymorphism of allergic rhinitis]. PMID- 26281051 TI - [Clinical analysis of nasal resistance and pulmonary function testing in patients with chronic nasal-sinusitis and nasal polyps]. AB - OBJECTIVE: To study the pulmonary function and nasal resistance characteristics of patients with chronic nose-sinusitis and nasal polyps (CRSwNP), to explore the evaluation role of nasal resistance in nasal ventilation function and the effect of endoscopic sinus surgery on pulmonary function in patients with CRSwNP. METHOD: Fifty CRSwNP patients that met the study criteria were selected . The patients were performed endoscopic surgeries according to Messerklinger surgical procedures under general anesthesia. Extent of surgery was based on preoperative CT showing the range of the lesion of disease and endoscopic findings. Perioperative treatments contained intranasal corticosteroids, cephalosporin or penicillin antibiotics, nasal irrigation and other treatments. Main outcome measures included visual analog scale (VAS), endoscopic Lind-Kennedy scores, nasal resistence, pulmonary function in patientsone week before and after surgery, three months and six months after surgery. Pulmonary function includes forced expiratory volume in one second (FEV1), forced vital capacity FEV1/FVC and peak expiratory flow (PEF). RESULT: The study found that there were significantly positive correlations among VAS score, Lund-Kennedy score and nasal resistance (P < 0.05) in CRSwNP patients, but there is a significantly negative correlation between VAS score, Lund-Kennedy score, nasal resistance and pulmonary function indexes of FEV1, FVC and PEF (P < 0.05). The VAS score, Lund-Kennedy score and nasal resistance values of CRSwNP patients were decreased significantly after comprehensive treatments with nasal endoscopic operation as the major one, the difference was statistically different (P < 0.05). And the pulmonary function indexs (FEV1, FVC, PEF) were significantly increased after surgery in CRSwNP patients. CONCLUSION: The nasal resistance can objectively and reliably reflect the degree of nasal congestion and the recovery of nasal function in CRSwNP patients after endoscopic sinus surgery. The detection method of nasal resistance is simple. Functional endoscopic sinus surgery can effectively improve the pulmonary ventilation function in CRSwNP patients, providing some clinical references about the prevention and treatment of CRS related lower respiratory disease. PMID- 26281052 TI - [Clinical observation of functional endoscopic sinus surgery associated with radiofrequency ablation of inferior turbinate for chronic rhinosinusitis]. AB - OBJECTIVE: To explore the clinical efficacy of functional endoscopic sinus surgery (FESS) associated with radiofrequency ablation on chronic sinusitis. METHOD: Fifty-four patients with chronic sinusitis were divided randomly into two groups: the study group and the control group, The study group received FESS associated with inferior turbinate lateral fracture and radiofrequency ablation treatment, while the control group received FESS associated with inferior turbinate lateral fracture treatment. RESULT: The SNOT-20 score, Lund-Kennedy score, mucociliary clearance time and nasal airway resistance of the patients in the two groups after treatment were significantly improved than those before treatment (P < 0.05), and the sense of nasal congestion, headache and face pain, purulent rhinorrhea, postnasal drip, and other symptoms were also relieved. After treatment, the scores of SNOT-20 and the scores of Lund-Kennedy in the study group were significantly lower than those in the control group (P < 0.05), but no significant difference was found in mucociliary clearance time between the two groups after treatment. CONCLUSION: FESS associated with radiofrequency ablation surgery is safe and effective for chronic sinusitis. PMID- 26281054 TI - [Clinical comprehensive treatment of refractory chronic rhinosinusitis]. AB - OBJECTIVE: To study the methods and efficacy of comprehensive treatment on retractory chronic rhinosinusitis(CRS). METHOD: Thirty-two cases of patients with refractory rhinosinusitis took part in individualized comprehensive treatment program, that is, a healthy diet and moderate exercise, psychological counseling, and reasonable operation and gauze changing, and rational use of drug therapy. RESULT: All patients were followed up for 6 months or more, 26 cases (81.3%) were completely controlled of the disease, 6 cases (18.7%) were partially controlled; the total effective rate was 100%. CONCLUSION: In the current situation that CRS etiology and pathogenesis studies have not yet made a breakthrough, and we have not developed a new and effective drug, comprehensive treatment focusing on internal and external factors of refractory rhinosinusitis at the same time, that is, to take a rational healthy diet, moderate exercise, psychological counseling, and reasonable operation and gauze changing, and rational use of drug therapy ect. can obtain better effect. PMID- 26281053 TI - [The efficacy and safety of budesonide inhalation suspension via transnasal nebulization compared with oral corticosteroids in chronic rhinosinusitis with nasal polyps]. AB - OBJECTIVE: To evaluate the efficacy and safety of a short course of nebulized budesonide via transnasal inhalation in chronic rhinosinusitis with nasal polyps. METHOD: Fifty patients with severe eosinophilic nasal polyps were randomized devided into study group (n = 25) and control group (n = 25). The study group received budesonide inhalation suspension (1 mg twice daily) via transnasal nebulization for one week and the control group received oral prednisone (24 mg QD). Visual analogue scales (VAS) of nasal symptoms, endoscopic polyp scores (kennedy scores) and morning serum cortisol concentrations were assessed in both groups pre- and post-treatment. Operation time and surgical field bleeding were evaluated. RESULT: Four subjects dropped out in control group. Budesonide transnasal nebulization caused a significant improvement in all nasal symptoms especially nasal obstruction (baseline: 8.25 +/- 0.53; after treatment: 4.97 +/- 0.97, P < 0.01) and reduced polyp size significantly (baseline: 4.64 +/- 0.63; after treatment: 3.40 +/- 0.76, P < 0.01) compared to pre-treatment. The patients treated with oral prednisone, however, showed more obvious improvement in nasal symptoms and polyp size, shorter operation time and better surgical field than budesonide group. Additionally, the morning serum cortisol concentration was mildly decreased after one week treatment in budesonide group [baseline (17.18 +/ 2.83) MUg/dl, after treatment (16.24 +/- 2.93) MUg/dl, P > 0.05], but all values were still located in normal range (normal range: 5-25 MUg/dl). Conversely, the morning serum cortisol concentration in oral prednisone group was lower than normal limit [baseline (18.19 +/- 2.81) MUg/dl, after treatment (2.26 +/- 0.70) MUg/dl, P < 0.01]. CONCLUSION: Twice daily budesonide transnasal nebulization is an effective and safe treatment as evidenced by significant improvements in nasal symptoms and reduction in polyp size, coupled with an absence of hypothalamic pituitary-adrenal axis suppression, which is safer than the systemic corticosteroids. Budesonide transnasal nebulization offers a viable treatment option for CRSwNP before operation. PMID- 26281055 TI - [Clinical analysis of revision endoscopic sinus surgery for recurrent chronic rhinosinusitis]. AB - OBJECTIVE: To investigate the therapeutic effect of revision endoscopic sinus surgery for recurrent chronic rhinosinusitis. METHOD: Clinical data of 45 cases of recurrent rhinosinusitis treated in our hospital were retrospectively analyzed. Revision endoscopic sinus surgery was performed in all the patients. RESULT: All the patients were followed up for a period of 1 to 2 years after operation. No serious complication occured. The cure rate was 75.6% (34 cases), 8 cases (17.8%) improved, while other 3 cases (6.6%) were of no effect. CONCLUSION: Recurrent rhinosinusitis is closely related with medical treatment before the surgery, adhesion in nasal cavity after the surgery, deviation of nasal septum, treatment of superior turbine and inferior turbine and regular medicament management after the surgery. Revision endoscopic sinus surgery is an effective method for recurrent recurrent rhinosinusitis. The efficacy of revision endoscopic sinus surgery can be greatly improved by reasonable perioperative management, skilled operation and regular follow-up postoperatively. PMID- 26281056 TI - [Clinical efficacy analysis of adult sinonasal rhabdomyosarcoma]. AB - OBJECTIVE: To investigate the clinical prognostic impact factors of adult sinonasal rhabdomyosarcoma (SNRMS). METHOD: The clinical features, treatment methods, and disease outcome were reviewed retrospectively for twenty-three adult SNRMS between 2006 January and 2014 December. The survival analysis was performed by Kaplan-Meier estimate and the comparison between groups by Log-rank test. Multivariate analysis was carried out by Cox proportional hazard model. RESULT: Patients' ages ranged from 18 to 59 years (median, 23.2 years). With a median follow-up of 20 moths (3-47 moths), 14 cases dead and 9 cases alive, the 1-year and 2-year overall survival (OS) rates were 77.1% and 35.0%, respectively. Within the 1-year and 2-year OS rates,early stage group had a higher overall survival rates than advanced diease group (100.0%, 66.7% and 83.3%, 10.5%, P < 0.05); combined therapy group had a higher overall survival rates than single treatment group (86.7%, 50.0% and 50.8%, 0, P < 0.05). In the non-metastasis group (21 cases), 1-year and 2-year distant metastasis rates were 38.1% and 70.5%, respectively. Multivariate analysis showed that radiotherapy, chemotherapy and tumor diameter less than 5 cm were good prognostic factors (P < 0.05), while the lymph node metastasis, meningeal involvement and orbital involvement were poor prognostic factors (P < 0 05). In the 14 cases of dead patients, 92 8% (13/14) died of distant metastasis. CONCLUSION: Adult RMS had a high advanced rate with poor prognosis. Distant metastasis is the leading cause of death. Controlling distant metastasis is a key to improve the survival rate. PMID- 26281057 TI - [Discussion IL-33 and its receptor ST2 associated with the pathogenesis of allergic rhinitis]. AB - OBJECTIVE: To study the expression of IL-33 and its receptor ST2 in the nasal mucosa of allergic rhinitis (AR) patients, and to explore the role of IL-33 and ST2 in the pathogenesis of AR. METHOD: Collected 24 cases of nasal septum deviation of patients with AR as AR group,and selected 20 patients with simple septum deviation as normal control. In addition, collected 20 cases diagnosed with AR, who accepted standardized specific immunotherapy(SIT). RESULT: Immunohistochemical results found more positively stained cells of IL-33 and ST2 in AR patients than normal control group, the difference was statistically significant (P < 0.05), Western-Blot detected that IL-33 and ST2 protein level were significantly higher in AR than the normal control group (P < 0.01), PCR detected that the expression of IL-33mRNA and ST2mRNA were increased in AR group compared with the control group, the difference was statistically significant (P < 0.05). While, the serum IL-33 levels in AR were decreased before treatment (72.37 +/- 16.18) ng/L than after six months of SIT (47.35 +/- 10.59) ng/L,and the difference was statistically significant (P < 0.05). CONCLUSION: IL-33 and its receptor ST2 were highly expressed in the nasal mucosa of patients with AR, suggesting that IL-33/ST2 may play an important role in the pathogenesis of allergic rhinitis. Serum levels of IL-33 were significantly decreased after SIT treatment, suggesting that IL-33 may have a positive correlation with the severity of AR. PMID- 26281058 TI - [Anti-EGFR monoclonal antibodies in locally advanced head and neck squamous cell carcinoma: a Meta-analysis]. AB - OBJECTIVE: To perform a Meta-analysis of all randomized controlled trials that compared the efficacy and adverse events profile of Mabs for LA HNSCC. METHOD: Several databases were searched, including CBM, PUBMED, EMBASE, and CENTRAL. Primary outcomes included overall response rate (ORR), overall survival (OS), progression-free survival (PFS). Secondary outcomes included serious adverse events, such as grade 3-4 skin reaction, dysphagia, mucositis, and nausea/vomiting. The results were expressed as relative ratio (RR) or hazard rate (HR) with their corresponding 95% CI. RESULT: The final analysis included 10 trials. The primary analyses indicated that Mabs did not improve ORR and PFS, except OS for locoregionally advanced (LA) HNSCC [ORR 1.21, 95% CI (0.97 - 1.49); PFS 0.87, 95% CI (0.75 - 1.01); OS 0.82, 95% CI (0.71 - 0.95)]. Analysis of adverse effects demonstrated that grade 3 - 4 skin reaction ERR 1.87, 95% CI (1.11 - 3.16)] was statistically significantly associated with Mabs except dysphagia ERR 0. 95, 95% CI (0.75 - 1.19)], Mucositis ERR 1.03, 95% CI (0.67 - 1.57)], and nausea/vomiting ERR 1.15, 95% CI (0.71 - 1.86)]. CONCLUSION: Anti EGFR Mabs may be satisfactory for improving OS of LA HNSCC. During the Mabs therapy, skin reaction should be much more monitored. PMID- 26281059 TI - [Application of gastric pharyngeal anastomosis assisted by laparoscope and a report of 4 cases]. AB - OBJECTIVE: To explore the clinical application of gastric pharyngeal anastomosis assisted by laparoscope. METHOD: Apply laparoscope in the gastric pharyngeal anastomosis for 4 cases of advanced hypopharyngeal carcinoma and cervical esophageal carcinoma patients. RESULT: Gastric pharyngeal anastomosis assisted by laparoscope were successfully completed in all 4 patients, all patients avoided thoracotomy or laparotomy, one patient occurred pharyngeal fistula, and died six months later. One patient had cervical lymph node metastasis a year and a half later, without treatment again because of economicissue. The remaining two patients were still alive, one patient had survived 3 years and a half after operation, the other had survived 2 years and a half after operation. CONCLUSION: Gastric pharyngeal anastomosis assisted by laparoscope is feasible. It can reduce the operation wound, improve the safety of operation and patients' life quality. PMID- 26281060 TI - [The impact of hypoxia improvement on laryngeal squamous cell carcinoma chemotherapy]. AB - OBJECTIVE: To evaluate the effect of hypoxia improvement in Hep-2 cell on cisplatin-induced apoptosis. METHOD: Human laryngeal squamous cell carcinoma Hep 2 cells and HIF-1alpha-RNAi-Hep-2 cells were cultured in normoxic, hypoxic and reoxygenation condition. The inhibition of cisplatin on cell proliferation was evaluated by MTT assay. The influence of cisplatin on cell cycle and apoptosis were detected by flow cytometry. RESULT: The inhibition of cisplatin on cell proliferation was reduced by hypoxia. After HIF-1alpha gene was silenced, the inhibition of cisplatin on Hep-2 cell proliferation was increased apparently, but was still interfered partly by hypoxia. Hypoxia could induce cell apoptosis decreased and enhance chemotherapeutic resistance. After reoxygenation, cell apoptosis induced by cisplatin was increased significantly (P < 0.05). HIF-1alpha RNAi-Hep-2 cells under hypoxia also showed certain resistance to apoptosis but the sensitivity to cisplatin was higher than that of Hep-2 cells. When cells were returned from hypoxic condition to normoxic condition for some time, the apoptosis induced by cisplatin was increased significantly (P < 0.05). CONCLUSION: The improvement of hypoxic microenvironment with HIF-1alpha gene knockout could increase the sensitivity of Hep-2 cells to chemotherapy. PMID- 26281061 TI - [Clinical analysis of 6 cases with sinonasal malignant melanoma]. AB - OBJECTIVE: To explore clinical characteristics of sinonasal malignant melanoma and curative effect of the combined modality therapy. METHOD: Clinical data of 6 cases with sinonasal malignant melanoma was retrospectively analyzed. All patients received surgery and postoperative radiotherapy. In addition, 3 cases received postoperative chemotherapy which scheme was CDBT and bioimmunotherapy consisted of INF-alpha and IL-2 after surgery, of which, 2 cases received one cycle of preoperative chemotherapy. RESULT: Six cases were followed up. The survival time ranged from 15 months to 98 months. The average survival time was 62.7 months. Analyzed by direct method, the 1-year, 3-year and 5-year survival rates were 100%, 83% and 67% respectively. Three cases which received the combined modality therapy, of whch, 2 cases received preoperative chemotherapy have survived by now. CONCLUSION: The combined modality therapy should be adopted in case of sinonasal malignant melanoma with operation indication. For the patients who can not be operated recently Postbiopsy, it was beneficial to improve the efficacy of therapy that one cycle of preoperative chemotherapy and bioimmunotherapy should be implemented. PMID- 26281062 TI - [Effect of microRNA-205 on proliferation of laryngeal carcinoma cell line Hep-2]. AB - OBJECTIVE: To study the effect of microRNA-205 (miRNA-205) on proliferation of laryngeal carcinoma cell line Hep-2. METHOD: The expressions of miRNA-205 in 27 cases laryngeal carcinoma tissues and adjacent normal tissues were detected by Real-time quantitative PCR, the expression of PTEN protein was detected by Western blot. The expressions of PTEN were detected by Western blot after miRNA 205 inhibitor or miRNA-205 mimics was transfected into Hep-2 cells and Hep-2 cells proliferation was measured by CCK-8 kit. RESULT: The expression level of miRNA-205 was significantly higher in laryngeal carcinoma tissues than in adjacent normal tissues (P < 0.01), and the expression of PTEN protein was lower in laryngeal carcinoma tissues than in adjacent normal tissues (P < 0.01). The proliferation rate of Hep-2 cells was decreased significantly and the expression of PTEN protein in Hep-2 cells was increased significantly after miRNA-205 inhibitor was transfected into (P < 0.01), and the proliferation rate of Hep-2 cells was increased significantly and the expression of PTEN protein in Hep-2 cells was decreased significantly after miRNA-205 mimics was transfected into (P < 0.01). CONCLUSION: miRNA-205 might promote the proliferation of Hep-2 cells by regulating the expression of PTEN. PMID- 26281063 TI - [Surgical treatment for primary papillary thyroid cancer: a Meta-analysis]. AB - OBJECTIVE: To assess and compare the two procedures, total thyroidectomy (TT) and partial thyroidectomy (PT), for papillary thyroid cancer in terms of associated injuries, postoperative complication, recurrence rate and survival, so as to provide a reference and basis for surgical procedure option of this disease. METHOD: Strictly specified into the exclusion criteria, the combination of computer retrieval and manual retrieval and retrieval systems such as CNKI, Wang Fan, PubMed, central, CBM database. Total thyroidectomy and partial thyroidectomy for the treatment of patients with thyroid papillary cancer related literature were compared, with the retrieval time until December 31, 2013. RESULT: According to the retrieval strategy 4630 literatures were found, and 20 witch matched the exclusion criteria were left, all were retrospective study. TT and PT group of recurrent laryngeal nerve injury rate are 5.9%, 2.0% respectively [OR = 0.39, 95% CI (0.17 - 0.90), P < 0.05], TT and PT group of parathyroid injury rate are respectively 4.9%, 0.8% respectively [OR = 0.23, 95% CI (0.08 - 0.68), P < 0.01]. The TT group of 10 years survival rate is 95.24% - 100%, and the PT group is 96.8% - 99.2% [OR = 0.03, 95% CI (0 - 0.34), P < 0.01]. Unstaged, unstaged TT group' postoperative recurrence rate is 4.7%, while PT group is 12.6% [OR = 3.21, 95% CI (1.57 - 6.57), P < 0. 01]. Postoperative recurrence of stage I TT group and PT group are 4.9%, 7.8% respectively [OR = 3.82, 95% CI (1. 07-13.66) P < 0.05]; The rate of stage II TT group is 0.5%, while the rate of PT group is 15.9% [OR = 17.23, 95% CI (4.03 - 73.73), P < 0.01]. CONCLUSION: Different methods of primary thyroid papillary carcinoma surgical treatment can all obtaina good survival, but the rate of laryngeal recurrent nerve injury and parathyroid injury caused by partal throidectomy is relatively lower. As a result, partial thyroidectomy can be a good choice for early stage thyroid papillary carcinoma. PMID- 26281064 TI - [Expression and its significance of CD44 in SP cells of nasopharyngeal carcinoma]. AB - OBJECTIVE: Discussion of expression and its significance of CD44 in SP cells of nasopnaryngeal carcinoma. METHOD: Flow cytometry was used to sort cultured CNE-2 cells of nasopharyngeal carcinoma for obtaining CD44-SP and CD44+SP cells. Biological differences of CNE-2, CNE-2 SP, CNE-2 NSP, CNE-2 CD44+SP and CNE-2 CD44-SP cells were statistically analyzed by experiments such as cell migration experiments, plate clone formation assay, cell cycle analysis and sensitivity tests to chemotherapeutics. RESULT: Two point 3 perent of SP cells were extracted from CNE-2 cells of nasopharyngeal carcinoma, among which 36.5% was CD44+SP cells. Abilities of proliferation, cell migration and plate clone of CD44+SP cells were significantly higher than other cells (P < 0.01), and its tolerance to chemotherapeutics was significantly higher too (P < 0.01). CONCLUSION: The proportion of SP cells in nasopharyngeal carcinoma cells was small, but SP cells had strong activeness in the aspect of cell proliferation with a "seed" characteristic of tumor cells. As CD44+SP cells played an important role in proliferation and chemotherapy resistance of nasopharyngeal carcinoma, it indicated that CD44 can be one of the surface markers of SP cells of nasopharyngeal carcinoma. PMID- 26281065 TI - [Effect of intermittent hypoxia of sleep apnea on embryonic rat cortical neurons in vitro]. AB - OBJECTIVE: To investigate the effects of different pattens of intermittent hypoxia on the activity and apoptosis of primary cultured rat embryonic cortical neurons, and to evaluate the role of intermittent hypoxia in the mechanism of obstructive sleep syndrom induced cognitive function loss. METHOD: The embryonic cerebral cortical neurons were cultured in vitro and were identified by immunofluorescence. Cultured neurons were randomly divided into intermittent hypoxia group, intermittent normal oxygen group, persistent hypoxia group and the control group, and intermittent hypoxia group was divided into five subgroups according to different frequency and time-bound. Neurons were exposed in different modes of hypoxia. MTT colorimetry was used to detect the viability of the neurons, and DAPI colorated measurement was used to calculate the percentages of neuron apoptosis. RESULT: There were significantly different effects between all subgroups of intermittent hypoxia and the continued hypoxia group on neuronal activity and apoptosis (P < 0.01); Intermittent hypoxia groups with different frequency and time had no difference in neuronal activity and apoptosis (P > 0.05). CONCLUSION: The effect of intermittent hypoxia was more serious than that of continued hypoxia on neuronal activity and apoptosis; The impact of intermittent hypoxia on neuronal activity and apoptosis may be an important factor in obstructive sleep apnea related cognitive impairment. PMID- 26281066 TI - [Malignant meningioma in nasal cavity and paranasal sinuses: a case report]. AB - Female patients, 50 years old, have a recurrent unilateral aggravating headache for 5 years. Without runny nose, sneezing, nasal hemorrhage, smell or vision loss. Prefessional examination: there is a visible hoar neoplasm in the right middle nasal meatus With smooth surface and rich in vascular. The nasopharyngeal MRI shows that there is a occupancy lesion in the right nasal cavity and sinuses, well-demarcated, about 21. 5 mm x 25.5 mm x 37.0 mm. Angiofibroma is the most likely diagnosis. Postoperative pathological section shows that tumor are hypercellular, which contains big nucleus. Cells are spindle or short fusiform shape, there are stripes and nuclear division in some cells. There are vortex structures in partial region. Immunohistochemical examination shows: CD34(++), Ki 67 (< 5%), CD68(-), Des (-), NSE(+), S-100(++), SMA(-), EMA (+). Histopathologic diagnosis: atypical meningioma, some were differentiated to rhabdoid meningioma. The final diagnosis is malignant meningioma in nasal cavity and paranasal sinuses. PMID- 26281067 TI - [Giant nasal septalhaemangioma in pregnancy: one case report]. AB - A pregnant lady in her third trimester presented with a rapidly growing right sided nasal mass associated with epistaxis and nasal obstruction for six months. Examination showed a non tender, protruding mass completely occluding her right nostril. Wide surgical excision was done under anaesthesia. Histopathology revealed capillary haemangioma. In a gravid patient with a rapidly growing intranasal lesion, capillary haemangioma should be considered as a differential diagnosis. PMID- 26281068 TI - [Adult of Drosophila melanogaster parasitized in human nasal cavity: a case report]. AB - We reported a case of adult Drosophila melanogaster parasitized in nasal cavity of a 81-year-old woman who was living in Xuancheng City, Anhui Province now. She was admitted for treatment of cerebral infarction and water accumulation in the lungs in 2014 June. The patient was also suffering from secretory otitis media, a history of hypertension and heart stents were placed in 2007. A foreign body was found in the left nasal cavity during the preoperative examination process, and then the part of the inflammatory tissue was removed through the nasal endoscopy, and sent to our department for identification. There are three adults of Drosophila in paraffin-embedded biopsy specimens. The parasites length is approximately 3mm, with huge red compound eyes. The end of the body is tip, with 5 ring lines in back, has no dark spots. The abdomen of the parasites have seven sections. Tarsus of foot I have no sex comb on base, and they are male adult of Drosophila melanogaster after identification. After a thorough reviewing of medical history, we knew the patient began to sneeze violently and frequently six years ago. But there was no clear or purulent nasal discharge flowing, therefore did not attract attention. After removing the parasites the sneezing symptoms were relieved, and had no abnormal symptoms in the follow-up 6 months. PMID- 26281069 TI - [Hemangiopericytoma in nasal cavity: a case report]. AB - We report a case of a 46 year old female patient with nasal hemangiopericytoma. She complained of left nasal congestion, pus snot for 10 years, sometimes with left nasal bleeding. Physical examination: in the left nasal tract saw red soft neoplasm, roughness surface, easy bleeding when touched. Sinus CT shows: bilateral maxillary sinus, ethmoid sinus, sphenoid sinus and the left posterior nasal cavity lesions, considering inflammation with the formation of polyps, tumor not excluded. The left nasal cavity neoplasm biopsy shows: hemangioma of left nasal cavity. After admission in general anesthesia, we do transnasal endoscopic sinus openning operation and the left nasal cavity neoplasm resection. Postoperative pathological examination shows: the left nasal cavity hemangiopericytoma. Immunohistochemical showed: Vimentin(+), Smooth muscle actin(+), Desmin(-), endothelial cells CD31(-) and CD34(-). No postoperative radiotherapy or chemotherapy, no tumor recurrence. After one year of follow-up, the contact was lost. PMID- 26281070 TI - [Endoscopic removal of foreign body in nasal apex: a case report]. AB - We present a rare case report of foreign body of the nasal apex in a 22-year man who were hospitalized because of a bit of metal rebounded. There was slight bleeding at wound site with a feeling of pain and swelling. On physical examination, the apex lied in the median position with a bleeding cut about 3 millimeter in length. There was no visible stump on the cut or rupture in the nasal vestibular. Computed tomographic scan showed the abnormal high-density shadow in the nasal apex while the foreign body was located in the subcutaneous tissue of the antero-upper part of septal cartilage. The admitting diagnosis was foreign body in nasal apex. Endoscopic surgery was adopted to remove the foreign body. PMID- 26281071 TI - [Adult nasal metal foreign bodies: 2 cases report]. AB - To analysis the data of 2 patients who had nasal metal foreign bodies after the pressure cooker explosion, the main clinical symptoms include head facial swelling after trauma, nose bleeding, or vision loss, etc. Specialized examination: facial swelling, the left eye content of one patient has been removed, the other patient's right side of the nasal dorsal skin was missing, which diameter was about 1.5 cm, and nasal cavity was interlinked. We could see that metal foreign bodies blocked the bilateral nasal cavity of the two patients. And emergency CT examination showed that most of the nasal cavity reserved for high-density foreign body. Two patients were diagnosed: (1) metal foreign bodies after nasal trauma; (2) nose bleeding. PMID- 26281072 TI - [Progress in application of mesenchymal stem cells for nasal inflammation disease]. AB - Mesenchymal stem cells (MSCs) are adult stem cells which derived from the embryonic mesoderm. They have a high proliferative ability and can differentiate into various tissues of mesodermal origin including bone, cartilage and adipose tissue in vitro. Moreover, MSCs have also been shown to produce anti-inflammatory molecules which can modulate cellular and humoral immune responses. Because of their easy preparation, the capacity for self-renewal, multi-lineage differentiation and immunoregulatory effect, MSCs therapy becomes a promising tool in the treatment of tissue regeneration, anti-inflammation, and autoimmune diseases. In this review we will focus on the application of MSCs for nasal inflammation disease. PMID- 26281073 TI - [Laryngeal and tracheal stenosis caused by Wegener's granulomatosis]. AB - Wegener's granulomatosis (WG) is a multisystem disease characterized by necrotizing granulomatous inflammation and vasculitis. WG classically involves the upper airway, lung and kidneys. Otolaryngologic manifestations are often the presenting symptoms in WG, Subglottic stenosis is a less common, but a life threatening manifestation of WG, This paper studies about the laryngeal and tracheal stenosis diagnosis and surgical treatment of Wegener's granulomatosis in the past 20 years. PMID- 26281074 TI - [Localization of sentinel lymph node with indirect lymphography and the application in head and neck tumor]. AB - Whether the sentinel lymph node (SLN) metastasis has important clinical significance for the therapy and prognosis of tumor. Sentinel lymph node biopsy (SLNB) has became the most accurate clinical method to confirm the status of sentinel lymph node. And the key of the success of SLNB is the localization of SLN. The methods used to locate SLN mainly are blue dye tracer method, radionuclide tracer technique, blue dye tracer method combined with radionuclide tracer technique, indirect lymphography, NIR imaging, and photoacoustic imaging. This article demonstrates the principle, application method and contrast agents of the indirect lymphography and the application in head and neck tumor. PMID- 26281075 TI - [PUBLIC MEDICINE AND RESEARCH-- IMPORTANT AND CHALLENGING]. AB - Fellows who travel to the US are familiar with the American concept of combining clinical medicine and research. Research activity enforces reading, being updated, thinking creatively initiating, opening horizons, and being in contact with researchers all over the world. Thus, performing research is advantageous not only for research itself, the public, the patients and the knowledge, but also for the development of the researcher, the hospital, and the academic institute with which the hospital is affiliated. However, given the huge clinical workload and obligations, along with the shortage of physicians, the time consuming nature of research activity and the difficulties in obtaining research funds, it is certainly not obvious that clinicians can manage to conduct research and publish it. Decision makers, policy determinants and the individual drive to academic progress, encourage research activity by physicians, albeit the external support is commonly theoretical and moral, and is not commonly combined with time or appropriate resource allocation. In the current issue of "Harefuah", physicians from the Lady Davis Carmel Medical Center publish their own research and review articles. The hospital is the second largest in the Haifa region, providing services to a population of over a million people. The manuscripts reflect only a small sample of the research and clinical activities of the hospital. PMID- 26281076 TI - [CHALLENGING THE OPTIMAL NUMBER OF RETRIEVED OOCYTES AND ITS IMPACT ON PREGNANCY AND LIVE BIRTH RATES IN IVF/ICSI CYCLES]. AB - INTRODUCTION: Large numbers of retrieved oocytes are associated with higher chances of having cryopreservation of embryos. However, the process entailed exposes women to increased risk for ovarian hyperstimulation syndrome. Furthermore, mild ovary stimulation protocols are more patient-friendly and with less adverse effects. Only limited reports exist on the significance of the number of retrieved oocytes achieved in a single stimulation cycle. AIM: To investigate the optimal number of retrieved oocytes to achieve pregnancy and live birth. METHODS: This retrospective analysis included 1590 IVF cycles. Oocytes maturation, fertilization, cleavage, as well as pregnancy and live birth rates were analyzed according to the number of retrieved oocytes. RESULTS: Oocyte maturation, fertilization and cleavage rates were lower in cycles with more than 10 retrieved oocytes compared with other groups. Live birth rates were highest when the number of retrieved oocytes was 11-15. CONCLUSIONS: Retrieval of more than 15 oocytes was not associated with a significant increase in chances of conception and birth. DISCUSSION: The better oocyte quality with 10 or less oocytes retrieved could be the result of a possible interference with the natural selection, or the minimized exposure of growing follicles to the potentially negative effects of ovarian stimulation. Although the average number of available embryos was higher when more than 10 oocytes were retrieved, achievement of more than 15 oocytes did not improve IVF outcome in terms of pregnancy and delivery rates. SUMMARY: Analysis of 1590 IVF cycles including the frozen-thawed transfers shows that the best outcomes were achieved with an optimal number of 11-15 oocytes. PMID- 26281077 TI - [BRONCHIECTASIS--REVIEW OF LITERATURE AND CLINICAL CHARACTERISTICS OF BRONCHIECTASIS PATIENTS TREATED IN THE BRONCHIECTASIS CLINIC AT THE CARMEL MEDICAL CENTER]. AB - AIMS: Bronchiectasis is a suppurative lung disease characterized by wide and distorted bronchi, with daily cough and sputum production punctuated by infectious exacerbations. Etiologies are diverse, and treatment is multidisciplinary, consisting of lung hygiene with mucolytic agents and physiotherapy, anti-inflammatory agents and antimicrobial agents, as needed. This study aims to review the literature and describe the clinical and radiological characteristics of patients with bronchiectasis treated at the Bronchiectasis clinic at Carmel Medical Center. METHODS: We included patients with Lung bronchiectasis according to chest HRCT treated at the Bronchiectasis clinic. We reviewed retrospective data regarding etiologic work up, age symptoms developed, extension of bronchiectasis, Lung function, microbiology of sputum, number of exacerbations and hospitalizations. RESULTS: Seventy four,patients were included, 39 women, mean age--65.7 years. Average lung involvement was two Lobes. Etiologies were: 42% idiopathic, 19% post-infectious and immune deficiency 5.6%. Cultures were positive for S. aureus in 9.5%, H. influenza in 19%, S pneumonia (4.8%), P aeruginosa (41.3%), non tuberculous mycobacteria (9.5%) and other bacteria in 11%. Patients suffered an average of 2.2 exacerbations per year, with 0.45 hospitalizations per year due to exacerbation of bronchiectasis. Mean predicted FEVI in spirometry was 74.32 +/- 25%. Patients colonised with P aeruginosa suffered significantly more exacerbations and hospitalizations than patients without P aeruginosa colonization. CONCLUSIONS: Bronchiectasis led to significant morbidity with infectious complications. We suspect that there is under- diagnosis and under-referral of this condition. PMID- 26281078 TI - [VERTEBRAL OSTEOMYELITIS CAUSED BY RARE PATHOGENS--THE NEED FOR HIGH INDEX OF SUSPICION]. AB - Vertebral OsteomyeLitis (V.O.) is a rare event that usually presents insidiously and follows an indolent clinical course, making early diagnosis difficult. The most important infecting organism in V.O. is Staphylococcus aureus, followed by gram-negative bacilli. We describe herein two cases of V.O. hospitalized in our department during the same week, caused by rare pathogens--Streptococcus sanguis (viridans) and Bacteroides fragilis. V.O. must be recognized rapidly because delay in diagnosis and treatment can result in neurologic compromise and high mortality. Its prompt and accurate diagnosis depends on detailed knowledge of the disease along with a high index of suspicion, even in face of rare pathogens on bacteriology results. PMID- 26281079 TI - [OUTCOMES OF HEPATIC, PANCREATIC AND GASTRIC SURGERY IN THE ELDERLY POPULATION: MORBIDITY, MORTALITY AND RESPONSE TO ONCOLOGIC TREATMENT]. AB - INTRODUCTION: There is a continuous rise in the proportion of elderly people in the general population. Previously, old age was a contraindication for numerous medical procedures. AIM: To assess the postoperative outcome of elderly patients who underwent major surgery of the liver, pancreas and stomach. MATERIALS AND METHODS: A retrospective analysis of patients aged 75 and older who underwent elective operations for malignant tumors of the stomach, pancreas and liver between January 2005 and December 2009 in the Department of Surgery A, at Carmel Medical Center. RESULTS: Of 258 operations, 80 (31%) were performed on patients older than 75 years; 46 (57.5%) were for males and 34 (42.5%) for females, with a mean age of 79 years. One patient was operated on twice. In 68 Patients (85%) the disease was primary and in 12 (15%) it was metastatic; 28 (35.4%) tumors were in the distal stomach, 13 (16.5%) in the proximal stomach; in the pancreas 13 tumors (16.5%) were in the head and 8 (10.1%) in the body/tail; 17 patients had liver metastases (21.5%1; 68 operations (85%) were performed in an open approach and 12 (15%) laparoscopically. Median hospital stay was 12 (+/-7.48) days and median ICU stay was 2 (+/-3.53) days. Median followup was 23 (+/-23) months. Complete records of 76 patients showed that 33 (43.4%) are alive with no evidence of disease; 12 (15.8%) were alive with stable disease; 25 (32.89%) died of cancer and 6 (7.8%) of other causes. DISCUSSION: These favorable results allow us to offer elderly patients the entire spectrum of surgical and medical procedures without considering advanced age as an absolute contraindication. CONCLUSIONS: Chronological age as a single parameter should not be a contraindication for radical medical treatment. PMID- 26281080 TI - [MYCOTIC ANEURYSM OF THE ASCENDING AORTA AND CEREBRAL INFARCTS IN A 17-MONTH OLD CHILD WITH KINGELLA KINGAE ENDOCARDITIS]. AB - Endocarditis is an uncommon presentation of Kingella kingae infection in children. A previously healthy 17 month old child was referred to our emergency department for evaluation of fever lasting eleven days, aphthous stomatitis and a new systolic murmur. Within a few hours of admission, antibiotic therapy was initiated for a presumptive diagnosis of bacteremia and within 24 hours after admission, gram negative coccobacilli were growing in the blood culture. In addition, echocardiography demonstrated a mycotic aneurysm of the ascending aorta with a mobile vegetation. The presumptive diagnosis of Kingella kingae endocarditis was made. Further evaluation by MRI revealed frontal and occipital cerebral infarcts. Due to the presence of presumed septic emboli in conjunction with progressive left ventricular dysfunction, the child was urgently taken to the operating room where aggressive debridement of the infected tissue was performed and the aortic aneurysm was repaired. The patient had an uneventful post-operative course. This case emphasizes the need for a high index of suspicion when evaluating children with community acquired infection. In addition, it also demonstrates the importance of early diagnosis and appropriate treatment of K. kingae endocarditis. PMID- 26281081 TI - [CYSTIC FIBROSIS SURVIVAL TRENDS IN CARMEL MEDICAL CENTER]. AB - INTRODUCTION: Cystic fibrosis (CF) is an autosomal recessive disorder. The disorder is caused by a mutation in the gene that encodes a protein which functions as a chloride channel. The chloride channel, cystic fibrosis transmembrane conductance regulator (CFTR) exists in the apical membrane of exocrine epithelial cells in the body. In the last 75 years the survival of CF patients has risen dramatically from a few months to the average age of 37 years. The rise in life expectancy is due to several reasons: improved medical treatment, treating patients in specialized CF centers, early diagnosis, respiratory physiotherapy and liver or lung transplantation. The purpose of this study was to review characteristics of our oldest living patients, transplantations and mortality of CF patients in our center. METHODS: Retrospective data have been collected regarding survival and other features in CF patients who were admitted to Carmel Medical Center in the years 2000 to 2013. RESULTS: One hundred and four CF patients were registered at the CF center between the years 2000 and 2013. Over this period 6 patients have passed away, all of whom were females. The average age of death was 21.4 years (not including one 10 months old baby who died from metabolic syndrome, not CF) with SD of 7 years, median of 20 and range of 17 years. The average age at the clinic is 22.5 years. The death incidence was less than 1% per year; the leading cause of death was respiratory failure. Of the living patients, ten patients are above the average survival age of 37 years. Four percent of the patients have undergone lung transplantation. CONCLUSIONS: CF is a multisystem disorder. In our center the mean age of death is in the third decade with an incidence of less than 1% per year, which is comparable to CF registries worldwide. Four percent of the patients have undergone lung transplantation. A gender gap with more female than male deaths was observed, a finding which was previously described in the literature. Life expectancy continues to rise as a result of early diagnosis, improved medical treatment and lung transplantation. As the age of survival rises, physicians with knowledge of adult internal medicine are needed to treat CF patients. PMID- 26281082 TI - [CLINICAL APPROACH TO PEDIATRIC SEROUS OTITIS MEDIA]. AB - Serous otitis media (also known as otitis media with effusion) is one of the most prevalent pediatric diagnoses. However, the recommended clinical approach and significance of this entity are controversial. Pathogenesis is usually based upon a combination of factors as overviewed in the body of the article. The cognitive and behavioral effects amongst children suffering serous otitis media were extensively studied and data points to little if any effects during long term follow-ups in otherwise healthy children. The therapeutic approach can be divided into watchful waiting, systemic drugs, topical drugs, mechanical therapies and surgical therapy (i.e. ventilation tube insertion). The reviewed literature mainly supports the effectiveness of the surgical approach in carefully selected cohorts of patients. PMID- 26281083 TI - [STATINS FOR THE PREVENTION OF CARDIOVASCULAR DISEASE AND DIABETES INCIDENCE--THE BENEFITS VERSUS THE RISKS]. AB - Statins (HMG-CoA reductase inhibitors) are first-line agents for the management of hyperlipidemia in patients at high risk of cardiovascular events and their use for cardiovascular disease prevention is clearly supported by clinical evidence. Although safe and generally well tolerated, there is growing evidence to suggest that statins are associated with an elevated occurrence of new-onset diabetes mellitus. The incidence of this adverse effect is not negligible, especially for specific subsets of patients. Statins remain the cornerstone for primary and secondary cardiovascular prevention, but specific attention to glucose metabolism and metabolic syndrome features should be given before and during statin treatment, especially in cohorts at greater risk, and a potential tailored statin treatment based on the patient's cardiovascular and metabolic risk profile might emerge as the safest therapeutic approach. The main purpose of this review is to discuss the clinical evidence regarding the association of statin use with new onset diabetes mellitus, the cardiovascular benefit/risk ratio with statins, and the rationale for individualized statin therapy. Future trials with adequate and long follow-up designed to assess the benefit/risk ratio of a specific statin will further refine the basis of this strategy. PMID- 26281084 TI - [PRENATAL GENETIC DIAGNOSIS-- "DAYS OF FUTURE PAST"]. AB - This review describes the history and the evolvement of prenatal genetic screening tests. We start in the era prior to the understanding that certain syndromes are genetic, continue through the identification of their genetic basis and the changes in markers in the pregnant woman's serum and conclude in the present when assays such as cell free D.N.A are offered to high risk women. PMID- 26281085 TI - [FROM STATISTICAL ASSOCIATIONS TO SCIENTIFIC CAUSALITY]. AB - The pathogenesis of most chronic diseases is complex and probably involves the interaction of multiple genetic and environmental risk factors. One way to learn about disease triggers is from statistically significant associations in epidemiological studies. However, associations do not necessarily prove causation. Associations can commonly result from bias, confounding and reverse causation. Several paradigms for causality inference have been developed. Henle Koch postulates are mainly applied for infectious diseases. Austin Bradford Hill's criteria may serve as a practical tool to weigh the evidence regarding the probability that a single new risk factor for a given disease is indeed causal. These criteria are irrelevant for estimating the causal relationship between exposure to a risk factor and disease whenever biological causality has been previously established. Thus, it is highly probable that past exposure of an individual to definite carcinogens is related to his cancer, even without proving an association between this exposure and cancer in his group. For multifactorial diseases, Rothman's model of interacting sets of component causes can be applied. PMID- 26281086 TI - [CANNABIS AND GLAUCOMA: AN ANCIENT LEGEND OR A NOVEL THERAPEUTIC HORIZON?]. AB - Glaucoma causes damage to the optic nerve and compromises the visual field. The main risk factor of the disease is the level of the intra-ocular pressure. Therapeutic options include medical and surgical treatment, aimed to lower the intra-ocular pressure. Consumption of the cannabis plant (Cannabis Satival has been known since ancient times. It can be consumed orally, topically, intra venous or by inhalation. The main active ingredient of cannabis is THC (Tetra Hydro-Cannabinol). One of THC's reported effects is the reduction of intra-ocular pressure. Several studies have demonstrated temporary intra-ocular pressure decrease in both healthy subjects and glaucoma patients following topical application or systemic consumption. The effect was a short term one. It was followed by the development of resistance to the drug after prolonged intake and it was also accompanied by topical and systemic side effects. Cannabis may be considered as a therapeutic option in glaucoma. Its limited effect, development of resistance, acquired side effects and the accompanying psycho-active influence limit its advantage and cause its efficacy to be dubious. Therefore, cannabis treatment for glaucoma currently seems impractical and is not recommended by either the Israeli or the American glaucoma societies. PMID- 26281087 TI - [THE ROLE OF SIMULATION IN SURGICAL TRAINING--A NEW ERA]. AB - Surgical training, which was traditionally based on the apprentice model, is undergoing a fundamental change since the introduction of virtual reality simulators into the training program of surgical residents. With the introduction of these simulators we can expect to see an improvement in the surgical abilities of new surgeons and a decrease in costs--as seen in the aviation world. Virtual reality simulators include a visual and tactile interface which is meant to train young surgeons in full procedure before the actual surgery. The available operation encompasses a multitude of surgical disciplines--gynecology, urology, orthopedics, vascular surgery, general surgery and more. The simulator allows the surgeon to practice complicated procedures and to be exposed to emergency situations without risking the patient's life. We opened in the Carmel Medical Center a multi disciplinary simulation center 18 months ago. The center includes simulators for gynecology, orthopedics, urology, general surgery, vascular surgery and advanced cardiac life support. The center cooperates with the Faculty of Medicine at the Technion in order to train young surgeons in all surgical disciplines. In this period of time we followed the improvement in the endoscopic abilities of the basic skills course participants. PMID- 26281088 TI - With changing technologies, changing models, and changing times ... What should lab directors consider when evaluating LIS options?. PMID- 26281089 TI - Collaborative data sharing and robust laboratory informatics solutions. PMID- 26281090 TI - Companion diagnostics: the key to personalized treatment of breast and ovarian cancer. PMID- 26281091 TI - Novel HER2 dual in situ hybridization (DISH): technique and implementation in routine laboratory testing.. PMID- 26281092 TI - Mitochondrial genetic disorders. PMID- 26281093 TI - 2015 LAB of the YEAR Children's Hospital of Wisconsin. PMID- 26281094 TI - Digital imaging: transformative new technology. PMID- 26281095 TI - An update on diagnostics for hepatitis C. PMID- 26281096 TI - CDC's HIV test algorithm matchesprotocol with latest technology. PMID- 26281097 TI - Diagnostic patenting since Myriad: an update. PMID- 26281098 TI - Cytology information systems revisited. PMID- 26281099 TI - Improving population health outcomes: top tips for care team collaboration. PMID- 26281101 TI - Laboratory preparedness: Ebola and other emerging infectious diseases. Now that the immediate crisis has passed, what have hospitals in the United States learned? PMID- 26281102 TI - Emerging viruses of North America: are labs ready? PMID- 26281103 TI - CDC updates Guidance for managing and testing possible Ebola clinical specimens. PMID- 26281104 TI - The renin-angiotensin-aldosterone system: increasingly complex and prevalent. PMID- 26281105 TI - The science of technology in the laboratory. PMID- 26281106 TI - The advent of digital microbiology. What are some of the benefits for early adopters in North America?. PMID- 26281107 TI - Copy number variation detection with next generation sequencing data: the impact on pharmacogenetics. PMID- 26281108 TI - The 2015 MLO annual salary survey. PMID- 26281109 TI - Epigenetics: DNA methylation assays. PMID- 26281110 TI - Prostate cancer diagnostic options: Past, present, and future. PMID- 26281111 TI - Presidential order combating antibiotic resistance will fuel laboratory and diagnostic innovation. PMID- 26281112 TI - Predictability of urinalysis parameters in the diagnosis of urinary tract infection: a case study. AB - Early diagnostic strategies to rule out uncomplicated urinary tract infections (UTI) or test of exclusion could significantly improve patient management in addition to providing optimal cost-effectiveness. We evaluated the predictability of dipstick parameters, with particular emphasis on leukocyte esterase (LE) and nitrite (NT) tests and microscopic urine sediment analysis as predictors of urinary tract infection in the setting of an urban university hospital. A total of 9,845 culture positive urine samples (7,095 females, 2,750 males; 8,938 clean catch, 907 catheterized specimens) collected over a period of twelve months from all patients seen at Temple University Hospital, Philadelphia, were included in this retrospective study. Dipstick and urinalysis data were independently correlated and compared with positive culture results. Either individually or in combination, LE and NT were positive in 30% (2,912/9,845), while both LE and NT were negative in 70% (6,933/9,845) of the total culture positive urine samples. There was no correlation of several other measured variables to culture positive urine samples. This study demonstrates that the uses of LE and/or NT are poor screening parameters as predictors of UTI, in the absence of additional clinical information. PMID- 26281113 TI - Determining myocardial infarction after PCI: CK-MB, troponin, both, or neither? PMID- 26281114 TI - IQCP and more: what's on the horizon for 2015? PMID- 26281115 TI - Quality control in clinical laboratory samples. PMID- 26281116 TI - Molecular monitoring for minimal residual disease. PMID- 26281118 TI - Achieving excellent drugs-of-abuse analysis starts with the proper sample preparation technique. PMID- 26281117 TI - Drugs of abuse: a challenging landscape for laboratories. PMID- 26281119 TI - ASM offers "enhanced precautions" for handling specimens from suspected Ebola, patients. PMID- 26281120 TI - U.S. transport labels: two changes to know about. PMID- 26281122 TI - The UNOS Renal Transplant Registry: Review of the Last Decade. AB - Kidney transplantation has become a preferred treatment for end-stage renal disease (ESRD) as transplant recipients enjoy freedom from dialysis and improvement in both quality and quantity of life. More patients are being placed on the transplant waiting list, although the waiting list patients still only represent a very small fraction of ESRD patients. The characteristics of both waitlisted and transplanted patients have changed considerably in the last decade, as the ESRD population has aged and waiting list times have increased. Over the last 10 years, we have witnessed an increasingly severe shortage of kidney donors. Even with increasing efforts of the transplant community to expand the donor pool by including larger numbers of high risk deceased donor transplants, the overall number of kidney transplants has remained relatively stable. Those who do receive transplants, however, benefit from excellent transplant outcomes. The use of paired exchange/chain transplant donors has increased the living donor pool significantly and with outstanding results. Belatacept, a costimulation blockage drug, represents a new class of transplant immunosuppression. It has been used sparingly in the first few years of its approval. Most kidney transplant patients are still maintained on immunosuppressive agents that were approved almost two decades ago. In the next decade, we will certainly continue to deal with an organ shortage as the number of eligible and waitlisted patients is likely to increase. Effective and efficient organ allocation policies will be increasingly necessary to address this scarcity. Optimizing the transplant candidate work-up, improving maintenance of waitlisted patients, and providing optimal post-transplant medical care will be vital to the continued success of kidney transplantation. PMID- 26281123 TI - Trends of Immunosuppression and Outcomes Following Liver Transplantation: An Analysis of the United Network for Organ Sharing Registry. AB - Advances in immunosuppression (IS) agents and strategies have resulted in reduced rejection rates and improved survival outcomes after liver transplantation. The use of induction and maintenance IS agents is both associated with reductions in acute rejection (AR) risk within the first 6 to 12 months posttransplant and with superior failure-free survival. With the lowered incidence of allograft losses attributable to rejection, the long-term sequelae of IS have become the major therapeutic challenge. The long-term use of calcineurin inhibitors and corticosteroids in maintenance immunotherapy regimens has been implicated in the development of renal dysfunction, infections, metabolic derangements, de novo and recurrent malignancies, and the propagation of hepatitis C virus reinfection. Our analysis of the United Network for Organ Sharing registry shows the use of induction and maintenance therapy is each associated with reductions in AR risk, thereby improving post-transplant survival. The administration of intensive induction regimens appears to be safe and exhibits an additive beneficial effect. Therefore, the use of intensive induction regimens may be warranted to allow for reductions in long-term maintenance IS to minimize drug toxicities while preserving graft outcomes. PMID- 26281124 TI - An Update on Cardiac Transplantation in the United States. AB - Heart transplantation in the United States remains an important option for those with heart failure. Survival rates over the last 25 years have improved with the advent of newer immunosuppressive agents, innovation, and a better understanding of managing risk. However, many patients continue to experience allograft failure after transplantation. Innovations in modalities to reduce acute and chronic rejection are needed to improve the long-term success of heart transplantation. PMID- 26281125 TI - Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients 2014 Data Report: Intestine. AB - As of September 19, 2014, 2441 cases of intestinal transplantation have been performed in 46 centers (2400 deceased, 41 living). Eight centers did more than 100 transplants. Annual case numbers peaked in 2007 (N = 198) and steadily decreased to 109 cases in 2013. Short gut syndrome (68%) and functional bowel problems (15%) are two major indications for intestinal transplantation. The 3 major types of transplants involving the intestine include: isolated intestine transplant (I); simultaneous intestine, liver, and pancreas transplant (I+L+P); and, combined intestine and liver (I+L) transplant. Graft survival has significantly improved in recent years, mainly due to improved first year graft survival. The 1-, 5-, and 10-year graft survivals were: 74%, 42%,and 26%, respectively (I); 70%, 50%, and 40%, respectively (I+L+P); and 61%, 46%, and 40%, respectively (I+L). The longest graft survivals for I, l+L+P, and l+L were 19 years, 16 years, and 23 years, respectively. Steroids, Thymoglobulin, and rituximab are 3 major induction agents used in recent years. Prograf, steroids, and Cellcept are 3 major maintenance agents. Induction recipients (68% of all patients) had a significantly lower acute rejection rate than nonrecipients before discharge (60% versus 75%, p < 0.001). Most of the patients received 2 (53%) or 3 (25%) maintenance immunosuppressants. Acute rejection episodes were usually treated with one (60%) or two agents (27%). Steroids were most commonly used (50-60%). OKT3 has been replaced with antithymocyte globulin (since 1999) and rituximab (since 2006). During 1990-2000, 94% (N = 445) of patients received ABO identical intestinal transplants, while 6% (N = 29) received ABO compatible transplants. ABO identical transplant recipients had a significantly higher 5 year graft survival rate than ABO compatible recipients (39% versus 21%, p < 0.0001). In recent years (2001- 2012), more patients received ABO compatible (N = 188, 11%) than in the early decade (p < 0.01). 5-year graft survival rates of ABO compatible transplants were lower than those of ABO identical transplants. However, the difference did not reach statistical significance (46% versus 49%, p = 0.07). The effect of ABO compatibility on graft outcome was further confirmed by Cox Analysis. ABO incompatible transplants are still rarely performed (N = 4) in intestine. In conclusion, annual case numbers of intestinal transplants have been decreasing, regardless of improved graft survival. ABO compatible intestinal transplants previously had a significantly lower graft survival rate than ABO identical transplants. However, the graft survival difference became less significant in recent years, possibly due to, or at least partly due to the use of new immunosuppressive agents. PMID- 26281126 TI - Intestinal Transplantation: International Outcomes. AB - Intestinal transplantation has continued to evolve over the past decade. Fewer patients have received intestine transplants in the past 5 years, perhaps due to efforts in intestine rehabilitation. Despite improvement in earlier outcomes, long-term survival has remained steady over the past decade. This is potentially due to the complications of immunosuppression, as well as inherent poor graft half-life due to chronic rejection. Improvements in outcome will require multidisciplinary efforts to understand the long-term mechanisms of intestine graft acceptance and to properly optimize and individualize immunosuppression for the transplant recipient. PMID- 26281127 TI - Deceased Donor Kidney Transplantation in Taiwan in 2015. AB - There were 1997 deceased donor renal transplants reported to the Taiwan Organ Registry and Sharing Center between April 1, 2005, and December 31, 2014. The median age of transplant recipients was 45 years, with most patients between 35 and 64 years old. The number of male patients was comparable to that of female patients. There were more blood type O patients than any other blood type. The 1 , 3-, and 5-year patient survival rates were 96%, 93%, and 89%, respectively. Graft survival rates at 1, 3, and 5 years were 94%, 88%, and 82%, respectively. Overall patient survival was significantly worse in patients with hepatitis B surface antigen (P = 0.0058). However, with respect to overall graft survival, there was no significant difference between patients with or without hepatitis B surface antigen (P = 0.100). Overall patient survival was significantly worse in patients with hepatitis C virus antibody (HCV Ab) compared to patients without HCV Ab (P < 0.0001). Likewise, overall graft survival was significantly worse in patients with HCV Ab compared to patients without HCV Ab (P < 0.0001). In order to promote willingness to be an organ donor, the following law was passed: if any person becomes a deceased organ donor, up to three of his or her blood relatives would have priority to receive a deceased donor organ should they be on the waiting list for transplantation. We do wish this organ allocation priority will be an incentive for deceased organ donors' families to think "to give is to take". PMID- 26281128 TI - Kidney Transplant Program at the Mayo Clinic in Arizona. AB - Since 1999, we have performed 2,302 kidney transplants at the Mayo Clinic in Arizona. Transplant volume has increased by 45% since 2010. Our center performed 269 kidney transplants in 2013. Our growth is related to multiple factors, including an experienced, committed team and strong support from our institution and referring nephrologists. Areas of program innovation at our center include: transplanting deceased donors with acute kidney injury, outcomes in older kidney transplant recipients, alemtuzumab induction with steroid avoidance, living donor paired kidney exchange-3 site experience, and other non-traditional deceased donor kidney transplants. Of the 162 acute kidney injury (AKI) donor transplants done at our program, 71% had severe AKI. The AKI donor kidneys had more delayed graft function; but graft survival, estimated glomerular filtration rate, and biopsy findings at 1 year were not different form the control group. We have transplanted 188 patients >= 70 years old at the time of transplantation. Graft survival at 1, 3, and 5 years was similar to that of patients < 70. Since 2008, 778 (37%) patients received alemtuzumab induction, therapy with excellent patient and graft survival. We have used steroid avoidance immunosuppression with excellent outcomes since 2003. Since starting kidney paired donation in 2009, it has resulted in 54 kidney transplants, including 4 compatible pairs. More than half of the deceased donor transplants done at our center are from non traditional donors such as Public Health Service increased risk, donation after cardiac death, extended criteria donors/high kidney donor profile index, and pediatric en-bloc donors. One- and 3-year graft survival of the non-traditional deceased donor kidney transplants are not different than the traditional deceased donor kidney transplants. PMID- 26281129 TI - 25 Years of Kidney Transplantation--A Period of Change. AB - At the University of Cologne Hospital, 1062 kidney transplants in adults and 136 pediatric transplants were performed between 1990 and 2014. Immunosuppressive therapy was changed during this time period from a therapy with anti-lymphocyte globulin induction followed by a triple therapy to a period using induction (IL2 receptor antagonists) followed by low dose tacrolimus, mycophenolate mofetil and steroids. Antiviral therapy has been constant during the 25 years, consisting of ganciclovir or valganciclovir. Major change occurred in the age of donors and recipients, with more than a third of both now being older than 65 years. Living donation has increased in number and proportion, at the same time the number of deceased donors rapidly declined. Longer time periods on dialysis resulted not only in an increased risk profile of the recipients, but were also accompanied by a significantly higher number of mismatches for the allocated kidney, since the relative importance of waiting time in the allocation process increased. Multivariate analysis showed that immunological factors such as HLA-match and panel reactive antibody are relevant factors, even in a single center analysis. PMID- 26281130 TI - The Thirty-Six Year Experience in Kidney Transplantation at Changzheng Hospital. AB - Between June 1978 and June 2014, 4,199 kidney transplants were performed at the Transplantation Center of PLA, Changzheng Hospital, Second Military Medical University. In our initial practice period (1978-1985), graft and patient survivals were 48.2% and 56.5%, 27.3% and 31.7%, 22.5% and 24.4%, 20.1% and 23.2%, and 16.5% and 20.8%, at 1, 5, 10, 15, and 20 years, respectively. These results improved tremendously after cyclosporine A (1986-1998) was used at our center. The rates of 1-, 5-, 10-, 15-, and 20-year graft and patient survival were 84.3% and 88.5%, 72.3% and 76.7%, 60.4% and 65.4%, 55.1% and 58.2%, and 49.0% and 51.8%, respectively. Tacrolimus (1999-2014) further increased graft survival to 95.1%, 84.4%, 77.1%, and 70.9%, and patient survival to 98.3%, 90.4%, 80.7%, and 73.4%, at 1, 5, 10, and 15 years, respectively. Multivariate Cox analysis suggested that transplant year, delayed graft function, rejection, immunosuppressive regimen, and original disease were independent predictors of graft survival and that poor HLA matching with 5-6 mismatches had an adverse effect on graft survival compared with 1-2 mismatches. The major causes of patient death included infection (38.1%), cardio-cerebral accident (30.2%), and malignancy (16.3%). As one of the pioneer transplant centers in China, our greatest contribution to organ transplantation in China is our self-developed organ preservation solution (HC-A), which has been used in more than 100,000 grafts and for more than 30 years. PMID- 26281131 TI - Liver Transplantation at Mayo Clinic Florida. AB - Over the sixteen year history of liver transplantation (LT) at Mayo Clinic in Jacksonville, Florida (MCF), we have maintained a practice devoted to excellence in pre- and post-LT management for patients suffering from end stage liver disease. With an emphasis on quality, MCF has made several adjustments with the goal of better utilizing marginal grafts for both successful post-transplant outcomes and minimizing waitlist mortality. This systematic approach is most exemplified in our experience with donation after cardiac death (DCD) liver allografts. Understanding the events during procurement has been critical to reducing the complications associated with donor warm ischemia time that are unique to DCD allografts. Better matching of donors to recipients has helped identify patients who are safe to receive more marginal grafts with successful patient and graft survival. Recognizing the spectrum of degree of sickness in patients undergoing LT, we implemented a multidisciplinary approach that allows for the avoidance of the intensive care unit after LT. In these ways, MCF continues to distinguish itself as an innovator in the field of transplantation for the benefit of continued better care for our patients suffering from end stage liver disease. PMID- 26281132 TI - The New Zealand Liver Transplant Unit: Auckland District Health Board. AB - New Zealand is a geographically isolated country with 4.55 million inhabitants. It has endemic hepatitis B (HBV) infection that is especially evident in Maori and Pacific Island communities and impacts indications for liver transplantation. The country has a socialised medical system that allows for full coverage of the assessment for, and completion of liver transplants in suitable recipients. Between February 1998 and December 2014, the New Zealand Liver Transplant Unit (NZLTU) had performed 595 liver transplants in 568 patients, indicating a crude re-transplant rate of 4.8%. Overall 1, 5, and 10 year patient survival rates for all adult (96%, 89%, and 81%, respectively) and pediatric (93%, 92%, and 92%, respectively) recipients compare very favourably with international outcomes from Europe and the United States. Eligibility criteria could be modestly expanded if deceased donor rates improved from the current level of around 10 per million of population per year. This somewhat meagre supply of deceased donor organs, along with significant waiting list attrition, has necessitated the use of living donors, which have been used in more than 50 recipients to date. Despite these limitations, the NZLTU has contributed to improvements in the outcome of transplantation for HBV and hepatitis C through the development of effective antiviral prophylaxis regimes. Furthermore, innovative changes have been made to the manner in which pediatric patients are transitioned to the adult service. PMID- 26281133 TI - The Alfred Hospital Lung Transplant Experience. AB - The management of patients undergoing lung transplantation has continued to evolve, leading to improvements in 90-day and 1-year survival. The significant advancements in donor management and utilization at our center have led to significant increases in lung transplant activity without any compromise in recipient outcomes. Through the use of a patient-centered multidisciplinary model of care involved in all aspects of recipient management, from assessment and waitlisting to pre-, peri- and post-operative care, our lung transplant outcomes represent 2015 world's best lung transplant practice. PMID- 26281134 TI - Efficacy of Intravenous Immunoglobulin in the Treatment of Persistent BK Viremia and BK Virus Nephropathy in Renal Transplant Recipients. AB - BK virus associated nephropathy (BKVN) can cause clinically significant viral infections in renal transplant recipients, leading to allograft dysfunction and loss. The usual management of BKVN involves reduction of immunosuppression and the addition of leflunomide, quinolones, and cidofovir, but the rate of graft loss remains high. The aim of this study was to assess the impact of treatment with intravenous immunoglobulin (IVIG) on the outcome of BKVN in renal transplant recipients. Upon diagnosis of BKVN, patients remained on anti-polyomavirus treatment consisting of reduction of immunosuppression and the use of leflunomide therapy. Treatment with IVIG was given only to patients who did not respond to 8 weeks of the adjustment of immunosuppression and leflunomide. All 30 patients had persistent BK viremia and BKVN with their mean BK viral loads higher than the baseline (range 15,000 - 2 millions copies/mL). Mean peak BK load was 205,314 copies/mL compared to 697 copies/mL after one year follow-up. Twenty-seven patients (90%) had positive responses in clearing viremia. The actuarial patient and graft survival rates after 12 months were 100% and 96.7%, respectively. IVIG administration appeared to be safe and effective in treating BK viremia and BKVN and in preventing graft loss in patients who had inadequate response to immunosuppression reduction and leflunomide therapy. PMID- 26281135 TI - Renal Transplant Outcomes in Waitlist Candidates with a Previous Inactive Status Due to Being Temporarily Too Sick. AB - BACKGROUND: In 2003, the United Network for Organ Sharing (UNOS) changed its policy to allow candidates with 'inactive' status to accrue time on the waitlist. In this study, we assessed the transplant outcomes among deceased donor kidney transplant (DDKT) recipients who were temporarily inactive specifically due to medical reason, i.e., being temporarily too sick (reason 7). METHODS: Using the UNOS database, adult DDKT recipients were divided into two groups: those who had never been inactivated (active group) and those with a history of being inactive due to reason 7 (reason 7 group). Patient and graft survival, 3-year risk of death, and graft failure were examined and compared. RESULTS: After 3 years of follow-up, patient survival in the reason 7 group was significantly lower than that of the active group (88.14% versus 91.93%, p < 0.01). The reason 7 group had a 20% increased risk of death (hazard ratio, HR 1.20, confidence interval, CI 1.04 - 1.38), a 16% increase in graft failure (HR 1.16, CI 1.06-1.28), and a 15% decrease in death-censored graft failure (HR 1.15, CI 1.01-1.31). CONCLUSION: Recipients with a history of reason 7 have lower patient and graft survival when compared to the active group. Nonetheless, the margins of difference are minimal. Candidates with a history of reason 7 should not be discouraged from transplantation once they return to active status. Standardized criteria for placing candidates on inactive status should be developed to reduce disparities among transplant centers. PMID- 26281136 TI - Update on Alloantibodies in Solid Organ Transplantation. AB - In the last few years, there have been studies published on serial testing and longitudinal analysis of anti-human leukocyte antigen (anti-HLA) antibodies. The focus of these studies was to determine specific characteristics of the impact of donor specific anti-HLA antibodies (DSA) in organ transplant dysfunction. These publications have led to an increasing concern about DSA and a growing effort to better understand DSA and to develop treatment for patients with DSA. In 2014, several reports were published that either confirm or expand upon both the understanding of the humoral theory and the clinical applications of DSA testing. This review delves into these publications and reports how their findings fit into the humoral theory of transplant. PMID- 26281137 TI - The Virtual Crossmatch: An Essential Tool for Transplanting Sensitized Patients. AB - Improved virtual crossmatch assessments following the implementation of solid phase HLA antibody immunoassays has significantly impacted transplantation of sensitized candidates, using either deceased or living donor organs. In deceased donor transplants, the virtual crossmatch has reduced the number of unexpected positive crossmatch tests resulting in improved organ allocation and reduced ischemia and wait times. The virtual crossmatch has also improved access to living donor transplantation by expediting donor evaluation by impacting clinical decisions regarding desensitization, and through implementation of successful kidney paired donation programs. However, continued improvements in predicting actual crossmatch outcomes are needed to further improve access to transplantation for sensitized candidates. Improved accuracy in HLA antibody strength assessments will allow for better correlations between transplant centers and the opportunity for collaborative trials to analyze transplant strategies and outcomes. PMID- 26281138 TI - Improved Long-Term Survival in Kidney Transplant Recipients with Donor-Specific HLA Antibodies After Mycophenolic Acid Escalation. AB - The development of donor specific antibodies (DSA) post transplant has been associated with chronic rejection and graft failure. In a longitudinal study, we have shown that increases in DSA precede rejection by months, thus allowing time for intervention. We hypothesized that mycophenolic acid (MPA) dose increases may reduce and/or stabilize DSA strength and also preserve renal function. Thirty stable DSA positive kidney transplant recipients participated in this Institutional Review Board approved, exploratory, open-label, single center study to assess the efficacy of MPA dose escalation in patients with DSA. MPA escalation was well tolerated and most patients were able to take higher doses for at least two years (duration of the study). In addition, MPA escalation is safe and participants had no significant side effects such as cytomegalovirus and BK infections. Long-term allograft survival of the MPA escalation group was superior when compared with the control group (p = 0.018). This pilot study indicates that escalation of MPA is safe and may stabilize DSA. In addition, five year follow up demonstrates improved long-term survival with MPA escalation compared with DSA positive recipients receiving the standard of care. Additional studies using larger cohorts are warranted. PMID- 26281139 TI - Impact of Donor Specific HLA Antibody Monitoring After Kidney Transplantation. AB - Kidney transplantation (KT) recipients with donor specific HLA antibodies (DSA) encounter higher rates of acute rejection and inferior allograft survival. We report our single center experience with prospective DSA monitoring and provide details of treatments utilized to overcome the potential impact of DSA in a cohort of predominantly African American adult KT recipients. Seventy-five flow crossmatch negative KT recipients underwent periodic screening for DSA utilizing the single antigen bead assay at 3, 6, 9, and 12 months post-transplant. Allograft biopsies were performed in the presence of DSA and/or evidence of graft dysfunction. The incidence of DSA was 23%, with a predominance of Class II antibodies. The rate of rejection was 6 times higher in DSA positive KT recipients compared to DSA negative patients (41% versus 7%, p = 0.004). In the DSA positive group, rejections occurred exclusively in the presence of de novo DSA and were predominantly antibody-mediated or mixed rejections. Despite a higher incidence of rejection in KT recipients with DSA, there were no significant differences in serum creatinine, graft survival, and patient survival between DSA positive and negative recipients at median follow-up of 18 months. DSA positive patients had significantly higher proteinuria compared to DSA negative recipients at 6 months, 1 year, and 3 years of follow-up. In conclusion, the detrimental effects of DSA on allograft function could be mitigated by serial DSA surveillance, protocol biopsies, and alterations in immunosuppression. With these measures, the improvement in graft survival in DSA positive KT recipients, at least at short-term, is encouraging. PMID- 26281140 TI - The Role of Donor-Specific Antibodies in Intestinal Transplantation: Experience at the University of California Los Angeles and Literature Review. AB - Intestinal transplantation is a viable treatment strategy for patients with irreversible intestinal failure for whom parenteral nutrition is no longer an option. Although improvements have been made in short-term post-transplant survival outcomes, long-term allograft loss, mainly to acute or chronic rejection, remains a major obstacle to successful transplantation. In all types of solid organ transplants, there is increasing evidence that antibodies directed against human leukocyte antigens, and in particular donor-specific antibodies (DSA), contribute to acute and chronic rejection as well as allograft loss. In this single-center review of intestinal transplant recipients, we report that the presence of pretransplant circulating DSA and the de novo induction of DSA posttransplant are both associated with increased risks of allograft loss. Although the cumulative incidence of acute rejection was not significantly affected by the presence of DSA, the power of this single-center study may be limited. Prospective, multicenter studies are needed to further elucidate the role of DSA in intestinal transplant recipients. In the published literature, there is a clear link between the presence of pre-formed DSA and early injury to the mucosal vasculature of the allograft. Two groups have reported an association between pretransplant DSA and the frequency of acute rejection episodes and subsequent graft loss. Similarly, studies investigating the effects of de novo DSA have demonstrated a relationship between the presence of post-transplant circulating antibodies and the occurrence of acute rejection and the risk of allograft failure. The use of a liver-containing graft appears to facilitate the clearance of pre-formed antibodies and prevents the de novo induction of post transplant antibodies. The most recent report stated that the de novo induction of DSA is concurrently accompanied by signs or rejection, such that the detection of circulating antibodies may signify impending graft injury, and supports the potential utility of DSA as a non-invasive biomarker for rejection in intestinal transplantation. PMID- 26281141 TI - High-Dose Intravenous Immunoglobulin Therapy for Donor Specific Antibodies in Kidney Transplant Recipients with Acute and Chronic Graft Dysfunction: Updates on Previously Reported Cohorts. AB - Kidney allograft damage resulting from donor-specific anti-HLA antibody (DSA) activity has been identified as a key component of long-term graft attrition. DSA that persists following acute antibody-mediated rejection (AMR) episodes and/or DSA associated with chronic graft dysfunction have been shown to be particularly pathogenic. Despite the significantly negative effects of DSA on graft survival, there are currently no accepted treatment modalities. We have previously reported our experience using a regimen of high-dose (5 mg/kg) intravenous immunoglobulin (IVIG) treatment over 6 months for kidney recipients with detectable DSA either following an acute AMR episode or in association with chronic graft dysfunction. In this manuscript, we report further follow-up on this cohort of patients treated with a single regimen of high-dose IVIG. We show a continued significant lowering effect on DSA present following AMR, particularly class I DSA, while DSA associated with chronic graft dysfunction, particularly class II, remains resistant to the immunomodulatory effects of IVIG. PMID- 26281142 TI - Highly Sensitized Patients: Miami Transplant Institute Experience. AB - BACKGROUND: Transplantation continues to be challenging in highly sensitized patients. Herein, we compared induction immunosuppression (IS) based on immunologic risk stratification and desensitization with intravenous immunoglobulin (IVIG). METHODS: Of the 42 highly sensitized kidney and 3 kidney pancreas transplant recipients who underwent IVIG for desensitization from 2008 2014, 10 (Control group) received standard induction IS with antithymocyte globulin, basiliximab, and methylprednisolone, and 35 (Rituximab group) received standard IS with rituximab +/- IVIG +/- plasmapheresis. Immunologic risk stratification was based on donor specific antibodies (DSA), flow crossmatch ratio, and calculated panel reactive antibody. All patients received tacrolimus, mycophenolate, and steroids for maintenance IS. Unacceptable antigen cut-offs for class I and II DSA were 6000 and 9000 mean fluorescence intensity and 2.0 and 4.4 channel shift ratios for T and B cell flow cytometry crossmatch, respectively. All complement dependent cytotoxicity T cell crossmatch negative patients were transplanted. RESULTS: Characteristics between groups, including high risk level, previous transplantation rate, number of human leukocyte antigen mismatches, delayed graft function rate, rejection rate, serum creatinine, and estimated glomerular filtration rate at 1 year (1.48 +/- 0.6 and 50 +/- 17 versus 1.1 +/- 0.4 mg/dl and 66 25 ml/min) were not statistically significant between the Control and the Rituximab groups, respectively. Waiting time for the Control group was 6.4 years versus 4.1 years for the Rituximab group (p = 0.009). The cumulative proportion of patients who remain free of death or allograft failure was significantly higher in the Rituximab (87%) versus the Control group (60%) (p = 0.047). CONCLUSIONS: In highly sensitized patients who received desensitization with IVIG, the addition of Rituximab to our standard IS (and/or IVIG and plasmapheresis as per the immunologic risk stratification model) resulted in higher cumulative patient and graft survival. PMID- 26281143 TI - Beyond Criteria and Definitions: Outcome of a Standardized Antibody-Mediated Rejection Protocol with a Diagnostic Schema Different from the Banff 2009 Criteria. AB - A new clinical diagnostic schema is needed for the diagnosis of antibody-mediated rejection (AMR) in kidney transplant recipients due to the limited utility of C4d staining, lack of standardized quantitative tests for donor specific antibodies, and potential new diagnostic markers. The treatment of AMR remains controversial because previous studies included heterogeneous treatment modalities, small sample sizes, and short follow-up time. At the University of Michigan Transplant Center, 26 patients were diagnosed with AMR based on our diagnostic protocol including C4d-negative AMR in thesetting of graft dysfunction and Banff tissue injury type II (capillaritis) or type III (arteritis). After diagnosis, these patients received six sessions of plasmapheresis (PP) and IVIG (100 mg/kg after the first to fifth PP and 500 mg/kg with the last PP). Our novel finding in this analysis was the association between persistent C1q detection and graft loss. We confirmed that C4d positivity at diagnosis is associated with worse outcomes. Also, we found that response to our treatment protocol is dependent on C4d staining and Banff tissue injury type. PMID- 26281145 TI - Effects of Two Preemptive Post-transplant Desensitization Regimens Upon Renal Allograft Survival and DSA Elaboration. AB - We used a simple point-based algorithm to identify patients who might benefit from desensitization because of their higher risk of antibody-mediated chronic rejection and graft failure. Points were assigned to known but easily determined risk factors (panel reactive antibody, flow crossmatch, delayed graft function) and calculated immediately after deceased donor kidney transplantation. Point totals were used to identify: 1) which patients would receive desensitization; and, 2) which regimen each patient would receive. This standardized approached resulted in improved overall graft survival in both modalities compared to historically untreated sensitized patients. While preemptive desensitization positively impacted clinical metrics, the improvements were unequal between regimens. PP/IVIG treatment clearly resulted in greater elimination of preexisting donor specific antibodies against HLA antigens (DSA), fewer late rejections, and superior 3-year graft survival among patients who resolved their DSA as well as those with persistent DSA. Since graft survival among PP/IVIG recipients was excellent even when preexisting DSA were still present one year post-transplant, it suggests that the benefit of this regimen is two-fold: first to increase DSA elimination among patients, and secondly, to minimize downstream immune activating events such as rejection. In contrast, IVIG patients with persistent DSA had more rejections and graft survival only slightly better than if they had no treatment at all. Since the IVIG group also had a preponderance of Class II directed DSA, we cannot discount the influence of that specificity upon graft outcomes. Additional studies are needed to confirm our findings and to allow more effective assessment of the impact of DSA specificity upon desensitization efficacy and graft success. PMID- 26281144 TI - Late Antibody-Mediated Rejection in a Large Prospective Cross-Sectional Study of Kidney Allograft Recipients--Preliminary Results of the Screening Phase of the BORTEJECT Trial. AB - There is limited data on the rate of late antibody-mediated rejection (ABMR) in unselected transplant cohorts. Here, we investigated the prevalence and characteristics of ABMR in a large cohort of long-term kidney allograft recipients. Patients were screened in the context of a randomized controlled trial (BORTEJECT study; ClinicalTrials.gov: NCT01873157) designed to investigate the impact of bortezomib on the course of late ABMR. The study (initiation in October 2013) includes a cross-sectional ABMR screening (key inclusion criterion: functioning graft at >= 180 days) to identify 44 recipients eligible for inclusion in the intervention trial. Patients were screened for donor-specific antibodies (DSA) applying solid phase technology and DSA+ recipients underwent protocol biopsies. Through November 2014, ABMR screening (after a median of 6.5 years post-transplantation) had been completed for 714 recipients. One hundred one patients (14%) had DSA above a threshold of 1,000 mean fluorescence intensity (MFI). Forty-four of 78 DSA+ recipients (6% of the overall cohort) subjected to biopsy were diagnosed with C4d-positive (n = 17) or -negative (n = 27) ABMR and 40 consented to participate in the intervention trial. DSA+ABMR+ and DSA+ABMR- patients differed significantly with respect to the MFI of the highest level DSA (P < 0.001), whereby ABMR or C4d positivity were moderately predicted by MFI values (area under the receiver operating characteristic curve: 0.75 and 0.84, respectively). In conclusion, the results of this cross-sectional analysis suggest a >= 6% prevalence of late ABMR. We demonstrate that the more frequent finding of circulating DSA may not necessarily associate with ABMR diagnosis, especially in patients with low antibody levels. PMID- 26281146 TI - Early Intervention in Living Kidney Transplantation Based on Dynamic Monitoring of Donor Specific Antibodies. AB - This study aims to analyze the clinical application of HLA donor specific antibodies (DSA) detected by Luminex single antigen beads and to discuss the impact of early intervention on renal function in DSA positive kidney transplant patients. In 64 cases of living-related renal transplantation, DSA was detected using Luminex single antigen bead assays before and after transplantation. The positive recipients were given intravenous immunoglobulin (IVIG) and increased doses of mycophenolate mofetil (MMF). The relationship between DSA and renal function was analyzed. In all transplant recipients, DSA was negative prior to transplantation. Ten DSA positive recipients were found after HLA mismatched transplantations. With intervention, two DSA positive recipients became DSA negative. In six cases, the patients' DSA intensity decreased more than 50%. In the remaining two cases, DSA intensity did not significantly decline, and within 3-6 months, antibody-mediated rejection (AMR) appeared and renal function was impaired. From our research, we conclude that dynamic monitoring of DSA using Luminex single antigen beads may help predict future changes in renal function. In addition, early application of IVIG and increasing doses of MMF can reduce the incidence of AMR. PMID- 26281147 TI - Higher Serum Trough Levels of Tacrolimus Increase 5-Year Allograft Survival in Antibody Positive Renal Transplant Patients. AB - BACKGROUND: The presence of human leukocyte antigen (HLA) and major histocompatibility complex class I chain-related gene-A (MICA) antibodies after transplantation is correlated with rejection episodes, proteinuria, and renal allografts loss. We assessed the clinical value of high-dose tacrolimus on post transplant HLA and MICA antibodies and proteinuria after renal transplantation. METHODS: Post-transplant sera of 310 renal transplantation patients who were negative for antibodies prior to transplant were tested by Luminex flow cytometry for HLA antibodies and MICA antibodies posttransplant. Once a patient was found to be antibody positive (Ab+), tacrolimus was dosed at two different concentrations: high tacrolimus Ab+ group (11 +/- 1.36 ng/mL average tacrolimus trough) or low tacrolimus Ab+ group (7 +/- 1.28 ng/mL average tacrolimus trough). Antibody negative (Ab-) patients were also studied and were given comparable tacrolimus doses to the low tacrolimus Ab+ group (7 +/- 1.28 ng/mL average tacrolimus trough). Proteinuria was measured using the pyrogallol method. All patients were followed for 5 years after renal transplantation. Associations between tacrolimus, proteinuria, and survival were analyzed. RESULTS: In the HLA or MICA Ab+ patients, proteinuria decreased after 5 years in the high tacrolimus Ab+ group unlike the low tacrolimus Ab+ group. Allograft survival in the high tacrolimus Ab+ group was significantly higher than the low tacrolimus Ab+ group and was similar to that of the Ab- group. CONCLUSIONS: High-dose tacrolimus might play a role in improving allograft survival in HLA or MICA Ab+ post-transplant patients. Increasing tacrolimus concentration might be a plausible treatment for Ab+ post-transplant patients. PMID- 26281148 TI - Combination of Total Lymphoid Irradiation, Low-Dose IVIG and ATG as Rescue Therapy for Highly Sensitized and Antibody-Mediated Rejection Renal Transplant Recipients. AB - Background: It is now clear that antibody- mediated rejection (AMR) is a major cause of graft failure. To avoid AMR, transplantation is preferably performed in non- or low-sensitized patients. For patients with pre-existing HLA antibodies due to pre-transplant sensitization or those with de novo HLA antibodies due to transplantation, elimination or reduction of HLA antibodies becomes critical to prevent AMR. Materials and Methods: In this clinical trial, we test the efficacy of a combination therapy of total lymphoid irradiation (TLI), low- dose intravenous immunoglobulin (IVIG), and anti-thymocyte globulin (ATG) with or without plasmapheresis (PP) in treating patients with HLA antibodies. Thirteen HLA antibody positive patients receiving renal transplants during 2009-2011 were enrolled in this study. Two cases with pre-existing HLA antibodies received combined therapy of TLI, PP, low-dose IVIG, and ATG induction. Eleven cases with de novo HLA antibodies and biopsy-proven AMR received TLI, low-dose IVIG, and ATG with or without PP. RESULTS: Two sensitized patients with pre-existing HLA antibodies were successfully desensitized and able to accept renal transplantation without an observable AMR episode in 12 months of post-transplant follow-up. In 11 AMR cases with de novo HLA antibodies, only one patient failed to respond to the therapy and lost the allograft. In the other ten cases, the follow-up biopsies at one year post transplant showed no evidence of rejection and the patients had stable renal function. B cell proliferation was persistently inhibited in both desensitization and AMR patients. CONCLUSIONS: Combined therapy of TLI, PP, low-dose IVIG, and ATG is an effective therapeutic measure to reduce the level of HLA antibodies and therefore to desensitize recipients pre transplant and to reverse AMR post transplant. The potential mechanism of the therapy involves inhibition of B cell proliferation. PMID- 26281149 TI - Treatment of Biopsy-Proven Acute Antibody-Mediated Rejection Using Thymoglobulin (ATG) Monotherapy and a Combination of Rituximab, Intravenous Immunoglobulin, and Plasmapheresis: Lesson Learned from Primary Experience. AB - BACKGROUND: Three strategies have been previously proposed to treat or prevent antibody-mediated rejection (AMR): (1) inhibition/depletion of antibody producing cells; (2) removal/blockage of antibodies; and, (3) inhibition of antibody mediated tissue injury. Here we test the efficacy of lymphocyte-depleting agent antithymocyte globulin (ATG) and triple therapy of rituximab, intravenous immunoglobulin (IVIG), and plasmapheresis in treating AMR. MATERIALS AND METHODS: Five biopsy-proven AMR patients were enrolled in this acute AMR treatment study. All patients received renal transplants from HLA highly mismatched donation after cardiac death (DCD) donors. Four patients received thymoglobulin (ATG) monotherapy at a dose of 75 mg/day for 5-8 days. One patient received a combination of rituximab (375 mg/m2), IVIG (50 g/day x2 days), and double filtration plasmapheresis (4x). Donor specific HLA antibodies (DSA), serum creatinine, and clinical signs and symptoms were used to determine the efficacy of anti-AMR treatment. RESULTS: All 5 patients developed AMR within 2 weeks after transplant. Two patients had class I DSA and 2 patients had class II DSA. One patient had both class I & II DSA. DSA in four patients (#1, 2, 4, 5) were pre existing and the levels of these DSA surged significantly within a week following transplant. The only patient (#3) without pre-existing DSA developed de novo DSA within 2 weeks post-transplant that rose rapidly regardless of anti-rejection treatment. All patients had positive C4d staining in peritubular capillaries. The proportion of B cells in all patients increased significantly above baseline level when patients experienced AMR. Even though both ATG and rituximab therapies successfully reduced the B cell proportion one week post anti-AMR treatment, their effects on DSA were not ideal. Patient #1 with mild AMR responded well to ATG monotherapy and DSA level steadily decreased from 2 weeks post-ATG treatment and became negative in the last follow-up test. The DSA levels in patient #2 with moderate AMR (ATG), #4 with mild AMR (ATG), and #5 with severe AMR (rituximab+IVIG+plasmapheresis) were reduced post treatment but remained at a level of 4,000-7,000 mean fluorescence intensity. Patients #2 and #4 had impaired renal graft function and severe AMR case #5 lost graft function and was back on dialysis from post-transplant day 12. Patient #3 with mild AMR (ATG) suffered from severe pneumonia 4 days after ATG treatment, which rapidly resulted in heart failure and the patient died on post-transplant day 36. CONCLUSIONS: All 5 AMR cases occurred in patients who received renal transplants from HLA highly mismatched DCD donors. Both ATG and rituximab had a significant depleting effect on B cells, but their effects on DSA were not ideal. Mild or moderate acute AMR was ameliorated but not cured by ATG monotherapy. For AMR patient with severe biopsy-proven graft injuries, B cell- and antibody-targeted therapies were not successful since they do not have immediate inhibitory or blocking effects on antibody-caused tissue injury. Therefore, anti-inflammatory, anti-coagulation and complement blockage agents should also be considered as part of an AMR treatment regimen in addition to strategies to remove or block DSA and to inhibit antibody production. PMID- 26281150 TI - Early De Novo Donor Specific Antibody Involvement in Delayed Graft Function After Kidney Transplantation: A Report of 2 Cases. AB - Kidney tubular damage caused by ischemia-reperfusion injury is considered the major cause of delayed graft function (DGF) after renal transplantation. It is not clear whether early generated de novo donor specific antibodies (DSA) play a role in DGF. Here, we report 2 cases of renal transplant with DGF, which seems to be associated with de novo DSA. When the early produced de novo DSA are not potent enough to mediate acute rejection, they may cause mild intra-graft injury, which has a significant impact on the degree of DGF and its recovery. Antibody targeted therapy seems to be beneficial to the recovery of patients with DGF. PMID- 26281151 TI - Allo-Hematopoietic Stem Cell Transplant in China: 2014 Update. AB - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides powerful curative weapons for patients with certain hematological diseases. Great improvements have been made within recent years, particularly in the fields of haploidentical HSCT, allo-HSCT for aplastic anemia, and strategies to overcome relapse and graft versus host disease. This review updates the current state of allo-HSCT in China. PMID- 26281152 TI - The Role of HLA Antibodies in HLA Mismatched Allogeneic Hematopoietic Stem Cell Transplantation. AB - Published reports suggest that engraftment failure after hematopoietic stem cell transplantation (HSCT) is closely associated with the presence of donor-specific HLA antibodies (DSA). Herein, we report a single cohort retrospective analysis of 567 cases of HLA mismatched allogeneic HSCT patients from the Lu Dao-pei Hematology Center, transplanted between September 11, 2012, and November 20, 2014. Of these cases, 306 patients underwent HLA class I and II antibody testing within one month before transplantation. For patients with HLA antibody screening resulting in an HLA antibody with a mean fluorescence intensity (MFI) > 1000, single antigen bead HLA class I and II testing was performed. Then, according to donor HLA genotype, we determined whether DSA were present. Of the 306 patients with pre-transplant HLA antibody screening (LABScreen Mixed Antigen), HLA class I antibodies were present in 51 cases (16.7%). HLA class II antibodies were present in 24 cases (7.8%). Of all antibody positive cases, 20 cases were positive for HLA antibodies on single antigen beads at an MFI > 1000. Half of these cases were DSA positive. Of the non-DSA antibody cases (n = 1 0), there was one case of primary graft failure after HSCT. In the ten DSA positive patients, the HSCT was chosen from the reactive donor. Seven of these cases were treated prior to HSCT with 1-2 times plasmapheresis or high-dose intravenous immunoglobulin (IVIG) therapy. The other three cases had no special treatment to decrease HLA antibodies before transplantation. All 10 DSA positive cases achieved successful engraftment. There was one case of primary graft failure in the group of 273 patients who were HLA antibody negative. Out of the group of 261 patients who did not undergo HLA antibody screening, there were 7 cases of primary engraftment failure. The incidence of engraftment failure was lower in the group of patients who had been screened for HLA antibodies prior to transplant than it was for the patients who had not been screened (2/306 versus 7/261, p = 0.054). Five of the 7 cases of engraftment failure were screened for HLA antibodies at 30 days after first transplantation. The results of five of the cases were negative for HLA antibodies and the patients underwent second transplants, all achieving successful engraftment. This cohort researched HLA antibodies and their effect on engraftment of HSCT in Chinese cases. We compared 306 patients who underwent HLA antibody screening and were given the appropriate treatment before HSCT if DSA were positive, with 261 patients who were not screened for HLA antibodies. We found that the incidence of primary graft failure significantly decreased. Although not directly determined, HLA antibodies (especially DSA) are the cause of engraftment failure and our findings reflect the importance of HLA antibody screening prior to transplantation. We suggest that patients with pre-existing DSA should be treated with plasma exchange or IVIG therapy before transplantation. PMID- 26281153 TI - [PEDIATRIC GASTROENTEROLOGY: ORIGINS, PROBLEMS, AND PROSPECTS OF THE RESEARCH]. AB - The nomenclature of digestive diseases in children was supplemented by the "new" diseases: of esophagus--gastroesophageal reflux disease (GERD), Barrett's esophagus, Zenker's diverticulum; of stomach and duodenum--gastroduodenitis, peptic ulcer disease, polyps, ectopic pancreas in the stomach wall; of the intestine--jejunitis, ileocolitis, Crohn's disease, celiac disease, bacterial overgrowth syndrome in the small intestine; of biliary tract--cholelithiasis, gallbladder cholesterosis, anomalies of the biliary tract; of pancreas--acute and chronic pancreatitis, annular pancreas (2). The features of gastrointestinal diseases in children experiencing the action of factors, not always positively affecting the growing organism, were established. These features include: presence of allergic background; high level of neuro-autonomous and psycho emotional changes in modern children, not only in schoolchildren, but even in preschoolers; polymorbidity or a combination (syntropy) of lesions of the digestive system; adverse outcomes of certain diseases as chronization, complications development, and as a consequence--a high risk of disability in children; "rejuvenation" of certain diseases of the digestive system (cholelithiasis, gallbladder cholesterosis, Crohn's disease), typical for adults. It is important to emphasize the clinical and social importance of gastroenterological diseases in childhood. Axiomatic is that the origins of many diseases of the digestive organs in adults lie in childhood. Early manifestation of certain diseases such as peptic ulcer disease, gluten enteropathy, Crohn's disease, and others, significantly impact the quality of life of sick children and their parents. It is worth to emphasize high costs of medical and prophylactic (tertiary prevention) activities using the drugs of latest generations. All this causes problems in both applied and scientific pediatric gastroenterology. PMID- 26281154 TI - [MORPHOFUNCTIONAL CONDITION OF THE UPPER GASTROINTESTINAL TRACT IN CHILDREN WITH OBESITY]. AB - The article is about the characteristics of the morphofunctional state of the upper gastrointestinal tract (UGIT) in children with obesity. Under supervision there were 130 children aged 10-16 years: study group--80 children with obesity (42 boys and 38 girls) (SDS BMI 2.0), the comparison group--50 children with normal body weight (32 boys and 18 girls) (SDS BMI from -0.99 to +0.99) with different disease UGIT. It is established that in children of the study group has a higher frequency of isolated motor-evacuation disorders (6.3% and 2.0%), and combinations inflammatory and functional disorders of UGIT (48.8% and 38.0%) compared with the comparison group. It is shown that functional changes UGIT in children with obesity are characterized by high frequency motor disorders, signs moderately expressed active chronic gastritis associated with H. pylori (58.3%), occurring against the background of minimal clinical symptoms, with a prevalence of focal nature of the inflammatory process on common. PMID- 26281155 TI - [METHOD FOR DETERMINING EROSIVE LESIONS OF THE GASTRIC MUCOUSA IN CHILDREN WITH JUVENILE ARTHRITIS]. AB - To detect the clinical diagnostic criteria for non-invasive diagnosis of erosive gastritis in children with juvenile arthritis have been studied the 92 children aged 9 to 16 years (mean age-13,9 +/- 2,3 years) with verified diagnosis of juvenile arthritis, of whom 10 had erosive gastritis (group 1) and 82 without erosions (group 2). A comparison of the groups on 23 grounds by analysis of contingency tables and the subsequent discriminant analysis, has developed a new non-invasive method for determining the erosive lesions of the mucous membrane of the stomach in children with juvenile arthritis, including a score of history, complaints and the results of laboratory studies the level of the G-17, pepsinogen I, pepsinogen II, and the ratio of pepsinogen I to pepsinogen II, the presence of autoantibodies to the H+, K+/ATPase of the parietal cells of the stomach, the test for occult blood "Colon View Hb and Hb/Hp". Developed a diagnostic table, including 11 features with scores each. The total score 27 or higher allows a high degree of probability to determine the erosive lesions of the gastric mucosa in children with juvenile arthritis. PMID- 26281156 TI - [DYNAMICS OF APOPTOTIC MARKERS (INTERLEUKIN-2 AND TNF-alpha) IN THE BLOOD SERUM OF CHILDREN WITH CHRONIC GASTRODUODENITES]. AB - The aim was to investigate apoptotic dynamics by IL-2 and TNF-alpha levels in the blood serum of children with chronic gastroduodenites. MATERIALS AND METHODS: There were examined 90 children with chronic gastroduodenitis. Cytokine level in the serum was studied at admission and in dynamics. RESULTS: Chronic gastroduodenitis is accompanied by the increase of IL-2 and TNF-alpha concentration thus reflecting the activity of apoptotic processes. The decrease of the markers' (IL-2 and TNF-alpha) levels after 10-11 days, 3 and 9 months after treatment indicates the decrease of apoptotic activity. In hyperplastic and atrophic gastritis there has been registered the highest and the lowest concentration of the markers, respectively. H. pylori contributes to the TNF alpha production mainly. PMID- 26281157 TI - [THE CORRECTION OF TROPHIC DISORDERS IN CHILDREN OF CHRONIC GASTRODUODENITIS WITH METHOD LOW-FREQUENCY LIGHT-MAGNETOTHERAPY]. AB - The results of a survey of school children with chronic gastroduodenitis when applying at an early period the medical rehabilitation with method low-frequency light-magnetotherapy. During treatment of hospital was evaluated vegetative trophic status with methods of cardiointervalography and thermovision functional tests. In normalizes clinical parameters was correction in dynamics of the vegetative status in children, it confirms the effectiveness of the therapy. It is proved, that the use of low-frequency light-magnetotherapy has a positive effect on the vegetative--trophic provision an organism and normalizes the vegetative dysfunction. PMID- 26281158 TI - [DETERMINING THE DEGREE OF DISRUPTION OF THE STRUCTURE OF THE LIVER AND THE SEVERITY OF PORTAL HYPERTENSION IN CHILDREN]. AB - AIM: To develop a system to define the degree of liver disruption and severity of portal hypertension in children based on the International Classification of Functioning, Disability and Health (ICF). PATIENTS AND METHODS: Studied the results of laboratory and instrumental methods 382 children: 267 patients with various liver diseases, including 49 patients who underwent liver transplantation, and 115 children without liver disease. RESULTS: Based on analysis of statistical data obtained were identified 10 indicators, a set of changes which can be used to assess the degree of disruption of the structure of the liver and the severity of portal hypertension: indicators that reflect the severity of fibrosis and cirrhosis of the liver (METAVIR score on a scale at fibroelastometrii, scores are Desmet at morphological study of the liver) and indicators that reflect the severity of portal hypertension (the diameter of the portal vein, splenic vein diameter, the length of the spleen, recanalization of the umbilical vein, esophageal varices, ascites, hydropericardium, hydrothorax). Each of the indicators was assessed on a 5-point system. Number of points reflects the sum of the changes of these parameters. Decrease the number of points on 0-4% (38-40 points) is regarded as a lack of structural failure of the liver and the severity of portal hypertension by 5-24% (30-37 points)--minor violations on 25-49% (20-29 points) -moderation disorders, 50-95% (3-12 points)- severe handicaps, 96-100% (0-2 points)--absolute violation. Studied the dynamics of children with autoimmune hepatitis, Wilson's disease and chronic hepatitis C. CONCLUSION: The proposed scoring system for assessing the degree of disruption of the structure of the liver and the severity of portal hypertension can be used as an objective criterion of the severity of the pathological process, to estimate the dynamics of defeat against the background of the therapy, determining the prognosis of the disease and as a criterion of the indications for liver transplantation. PMID- 26281159 TI - DIAGNOSTIC POSSIBILITIES OF HYDROCOLONIC ECHOGRAPHY AT CHRONIC CONSTIPATION IN CHILDREN. AB - On the basis of 15 years' of experience the criteria of assessment of the colon was developed when performing hydrocolonic echography (HCE) and the possibilities of HCE are evaluated at chronic constipations (CC) in children. A retrospective cross research of results of HCE in 263 children with CC aged from 14 days to 17 years was conducted. HCE allowed to evaluate the position of the colon in the abdominal cavity, gave information on lengthening and lumen of the colon, structure of the intestinal wall, haustra, peculiarities of the functioning of the colon in real time. Secondary changes of the colon due to CC, depending on intensity of CC are identified. Echographical characteristics of dolihocolon (light constipations) and dolihomegacolon (severe constipations) are given. Possibilities of echographical identification of the surgical provenance (diseases of Hirschsprung, Payr) of constipation in children are defined. CONCLUSION: Hydrocolonic echography grants high possibilities of diagnostics and allows identifying the organic reason of constipation in due time. In case of functional constipation, HCE narrows down the amount of additional examinations. Identification of secondary changes of the colon due to CC does hydrocolonic echography by the instrument of quality control of conservative treatment with the advantage of HCE of lacking radiation and the possibility of unlimited replication. PMID- 26281160 TI - [PROBIOTICS, NUTRITIONAL STATUS AND RESISTANCE TO RESPIRATORY INFECTIONS IN INFANTS]. AB - Aim of this study was to investigate the efficacy of prophylactic use of a liquid probiotic form based on Enterococcus faecium L3 in children first year of life to increase resistance to acute respiratory infections (ARI) in the winter-spring period and improve nutritional status. In a specialized (psychoneurologic) orphanage of St. Petersburg within three months of winter-spring period in 2014 observed 29 children in the first year of life. Observed children were randomly divided into two groups. The main group (n = 14) within three months received daily per os liquid probiotic form based on E.faecium L3 in a daily dose of 1.5 x 10(9) CFU. A control group of children (n = 15) was comparable with the main group by gender and age. The children observed groups studied the incidence of ARI; number of vaccinated children; the number of children who received two or more vaccinations at the same time; the number of children with acute infectious diseases within 1 month after vaccination; dynamics of Chulitskaya index, body mass index, body weight and length. The data obtained are subjected to statistical analysis, the results were considered significant at p < 0.05. The results showed that the use of probiotic forms E.faecium L3 in infants helped to reduce the average number of ARI cases per child (0.29 +/- 0.13 vs. 0.73 +/- 0.12 in the control group; p < 0.05) only in the first month of the observation that combined with a significantly higher BMI values increase this month (0.54 +/- 0.25 vs. 0.07 +/- 0.22 kg/m2 in the control group; p < 0.05). Use the liquid probiotic form E.faecium L3 in infants had a positive impact on overall health, which is reflected in the implementation of routine vaccination activities--in the main group, the number of children who received two or more vaccinations at the same time was 18.1% more. PMID- 26281161 TI - [ENZYME THERAPY OF POSTCHOLECYSTECTOMY SYNDROME IN CHILDREN]. AB - The article provides pathogenetic justification of the need and the effectiveness of enzyme replacement therapy (ERT) of postcholecystectomy syndrome (PHES) in children. Special focus will be on the possibility of using the ERT in PHES in children of different age groups. Personal experience with these drugs in children with cholelithiasis is provided, considering their mechanism of action and side effects of ERT. Advantages of Creon are demonstrated for correction of exocrine pancreatic function in PHES in children. PMID- 26281162 TI - [STEPPED DIET THERAPY OF ACUTE ENTERIC INFECTIONS IN CHILDREN]. AB - The article describes the main principles of stepped diet therapy of acute intestinal infections in children developed on the basis of nutritive support staging, depending on patients' age, stage and severity of disease. Significance of functional food products for diet therapy tactics in patients with mild and moderately severe forms of infection is demonstrated. PMID- 26281163 TI - [COMPARATIVE STUDY OF DE-NOL AND NOVOBISMOL IN REGIMENS ERADICATION IN PATIENTS WITH H. PYLORI--ASSOCIATED DISEASES]. AB - AIMS: The aim of this study is to assess efficacy and safety of reinforced H. pylori eradication therapy. METHODS: During 2013-2014, 40 outpatients were examined. The study included men and women 18-65 y.o. They have been devided in to 2 group by randomized choice (20 patients in each group). Patients were treated with the reinforced H. pylori eradication therapy: PPI (40 mg,/q12h), clarithromycin (500mg/q12h), amoxicillin (1000 mg/q12h), bismuth subcitrate (240 mg/q12h) for 10 days. The first group given bismuth subcitrate--De-Nol, the second group given Novobismol. Eradication was confirmed by a 13C-urea breath test and monoclonal stool antigen test 6-8 weeks after therapy. RESULTS: A total of 34 patients underwent eradication treatment. Two were lost to follow-up (one patient in each group), four patients (two patients in each group) did not complete treatment due to adverse events. The eradication rates were 97.1% (95% CI, 88.9% -100.0%) by per-protocol (PP) and 82.5% (95% CI, 69.4% - 92.5%) by intention-to-treat (ITT) in the two groups. The ITT analyses resulted in rates of 85% (95% CI, 66.5-96.9) for the 10-d reinforced therapy with DeNol and was 80% (95% CI: 60.2-94.1) for the 10-d reinforced therapy with Novobismol (P = 0.68), while the PP analyses resulted in 100% (95% CI, 94.5-100.0) and 94.1% (95% CI: 78.3-99.9), respectively (P = 0.31). CONCLUSION: The reinforced H. pylori eradication therapy (10-day high-dose PPI bismuth-containing standard triple therapy) achieves a significantly high eradication rates in patients with H. pylori - associated diseases. Both drugs (De- Nol and Novobismol) are both effective and safe for the first-line eradication of H. pylori. PMID- 26281164 TI - [LAPAROSCOPIC FUNDOPLICATION NISSEN--GOLD STANDARD TREATMENT OF GASTROESOPHAGEAL REFLUX IN CHILDREN]. AB - Gastroesophageal reflux is very common in children and often leads to reflux esophagitis, peptic esophageal strictures, Barrett's esophagus. If the conservative treatment fails a patient needs surgical treatment as well as those who suffer from complications and hiatal hernia. The most popular operation is laparoscopic Nissen fundoplication with the efficiency of more than 80%. However, the main challenge is redo fundoplications. Hiatal hernia and operation technique are considered to be the most probable risk-factors.In our study we introduce the new technique of laparoscopic Nissen procedure. It implies different way of the fundoplication wrap construction: in the first row we use sutures through all the layers of the stomach wall instead of seromuscular ones. Since 2010 more than 180 patients have been operated on with the incidence of recurrent reflux 2 times lower. PMID- 26281165 TI - [PRACTICAL RECOMMENDATIONS FOR SURGICAL TREATMENT OF COMPLICATIONS OF CROHN'S DISEASE IN CHILDREN]. AB - Practical recommendations are presented Grade 4. The article covered all possible methods of surgery, depending on the type and severity of the disease. It is noted that, despite the need for surgery and reoperations high frequency in most patients with complicated Crohn's disease yet there is a significant improvement, and pain disappeared for a while. Stressed that to achieve success in the surgical treatment of Crohn's disease by a single intervention can be extremely rare. A comprehensive approach to the treatment of complicated Crohn's disease, an important component of which is the appointment of preventive treatment after surgery. PMID- 26281166 TI - [CONGENITAL CHYLOUS ASCITES: A CASE REPORT]. AB - Congenital chylous ascites is a rare polietiologic entity, requiring close study of the infant's organism by visualization methods in order to diagnose the bening or malignant underlying pathology. In the article is given a report on case of congenital chylous ascites in infant, caused by lymphangioma in the peritoneal cavity. Atypical clinic and the lack of diagnostic standards led to the later detection of the ascite's origin. PMID- 26281167 TI - [THE CASE OF A COMBINATION OF TWO AUTOIMMUNE DISEASES: AUTOIMMUNE HEPATITIS AND IMMUNE THROMBOCYTOPENIA IN THE SAME PATIENT 13 YEARS OLD]. AB - The paper presents the case of a combination of two autoimmune diseases in the same patient. Describes the current ideas about the etiology of diseases and their treatment. Highlighted timely verification of diagnosis and differential approach to immunosuppressive therapy. PMID- 26281168 TI - [REPORT ON THE CONDUCT OF CONFERENCE "LATE DIAGNOSTICS OF CROHN DISEASE IN CHILDHOOD" (KANSHINA'S READINGS)]. AB - This article presents the conference report, summarizes the goals and directions of the conference, the review of reports. PMID- 26281169 TI - [EPIDEMIOLOGICAL STUDIES IN GASTROENTEROLOGY: LONG-TERM SIBERIAN EXPERIENCE OF HELICOBACTER PYLORI AND RELATED DISEASES]. AB - The paper presents the long-term experience of Siberian epidemiological studies in the field of gastroenterology (cross-sectional and prospective). High prevalence of Helicobacterpylori infection (75-85%) in the adult population of Siberia, and the association with dyspeptic symptoms in different age groups are shown. The dynamics of infection in children and adolescents, the high detection rates of CagA-positive strains, the prevalence of the different phenotypes of gastritis and the predictive value of gastric atrophy biomarkers in relation to gastric cancer were studied. The importance of epidemiological studies for the formation of groups at risk for a number of diseases and the development of prevention programs is demonstrated. PMID- 26281170 TI - [GASTROESOPHAGEAL REFLUXED DISEASE IN PERSONS WITH OBESITY AND LEPTIN RESISTANCE]. AB - AIM OR OBJECTIVE: to examine the levels of leptin and its soluble receptor in the serum of patients with gastroesophageal refluxed disease (GERD) with different weight. METHODS: We examined 125 patients with GERD. We asked patients, assessed an anthropometric indices, did a biochemical analysis of blood, ultrasonic studies of abdominal, endoscope examination of the esophagus and stomach, pH monitoring, assessed levels leptin and its soluble receptor. We separated patients in two groups: the main group (n = 105) - patients with overweight and obesity, the comparison group (n = 20) - with normal weight. RESULTS: Values of waist circumference, the hips, its relationship, level of glucose and triglycerides was higher in main group (p<0, (10) (10)3, p<0,00002, p<0,0096, p<0,02, p<0,008, respectively). Leptin levels in patients with obesity and overweight was significantly higher and the level of its receptors was significantly lower (mediana of leptin levels 29,81 (12,63-45,62) in main group versus 4,13 (3,03-5,79), mediana of leptin's receptors 18,74 (14,98-25,11) versus 31,82 (27,81-34,43), respectively). Between these indicators in main group was revealed negative correlation of moderate strength (rs= (-0,452), p<0,0004). In group with overweight and obesity a fairly significant correlation between the level of adipokines and severity of symptoms of GERD were found: negative correlation of moderate intensity between leptin and severity of dysphagia (rs= ( 0,259), p<0,05) and positive correlation of moderate intensity between leptin's receptor and severity of belching (rs= (-0,295), p<0,02). As well as a fairly significant positive association of moderate strength between leptin levels and the maximum value of pH in the stomach (rs= (-0,499), p<0,03) and between leptin's receptor and index relationship of pH in the cardia of the stomach to the body (rs= (-0,505), p<0,04) were found. CONCLUSIONS: leptinresistance in individuals with overweight and obesity is associated with features of GERD. PMID- 26281171 TI - [THE ROLE OF OXIDATIVE STRESS IN THE PATHOGENESIS OF GASTROESOPHAGEAL REFLUX DISEASE]. AB - AIM: To study features of lipid peroxidation in patients with different types of gastroesophageal reflux disease (GERD). METHODS: We examined 120 patients with different clinical variants of GERD and 25 healthy individuals. It was determined the concentration of diene conjugates (DC) ketodienes (KD), conjugated trienes (CT) by biochemical methods in serum and mucosal biopsies of the lower third of the esophagus. RESULTS: In biopsies of esophagus mucosa the content of DK, CD, CT was increased in patients with complications of GERD (ulcerative esophagitis and Barrett's esophagus) in 2,2-5,3 times compared with healthy individuals. In blood serum registered similar but less pronounced regularities. CONCLUSION: It was revealed a significant intensification of free radical oxidation in the tissues of the esophagus and the blood of patients with GERD, which was exacerbated in proportion to the severity of the disease. PMID- 26281172 TI - [ESPECIALLY CHRONIC RHINOSINUSITIS ASSOCIATED WITH GASTROESOPHAGEAL REFLUX DISEASE]. AB - OBJECTIVE: to study the clinical and laboratory features of chronic rhinosinusitis (CRS) associated with gastroesophageal reflux disease (GERD). MATERIALS AND METHODS: The study involved 87 patients with complaints of difficulty in nasal breathing and 30 healthy volunteers with no pathology ENT and GERD. The diagnosis of CRS met the criteria EPOS 2012. Diagnosis of GERD was performed based on the recommendations of the Montreal consensus. All investigated conducted a survey for the presence of esophageal and extraesophageal manifestations of GERD, fibroesophagogastroduodenoscopy, LOR examination with the use of endoscopes, rhinoscopy, laryngoscopy, computed tomography of the paranasal sinuses, pH-metry mucous secretions of the nose and pharynx using visual test - strips, microbiological examination of discharge from the middle of the nose stroke. Association of CRS with GERD with GERD compared with impaired nasal breathing inflammatory and non-inflammatory genesis in the absence of GERD and healthy volunteers accompanied by a large variety and frequency of symptoms, endoscopic signs of laryngitis back, reducing the pH of the pharynx, the change in quantitative and qualitative characteristics of the microflora of the nasal mucosa and paranasal sinuses. PMID- 26281173 TI - [NONINVASIVE DIAGNOSTICS OF THE PHENOTYPE OF GASTRITIS: ANALISIS OF THE FIRST THOUSAND OF CASES]. AB - The analysis of noninvasive diagnostics of a phenotype of gastritis among 1050 people aged from 18 till 80 years which consistently addressed to policlinic is presented in the article. The instrument of diagnostics was a <>, including a complex of biomarkers - so-called <> (pepsinogen I, pepsinogen II, gastrin-17 and IgG- antibodies to Helicobacter Pylori). High frequency of different variants of atrophic gastritis (25%) with a gastric cancer risk and conditions with a risk of erosive and ulcer damages of the stomach mucous (26 %) was shown. Clinical and economical expediency of noninvasive screening of a phenotype of gastritis is postulated. PMID- 26281174 TI - [THE EFFECTIVENESS OF ERADICATION IN PATIENTS WITH PEPTIC ULCER DISEASE ASSOCIATED WITH HELICOBACTER PYLORI, DEPENDING ON THE GENOTYPE OF THE DRUGMETABOLISM OF PROTON PUMP INHIBITORS]. AB - One of the most likely causes of the lack of effectiveness of eradication therapy of peptic ulcer associated with Helicobacter pylori, is a feature of omeprazole metabolism by cytochrome CYP2C19. The paper work presents evidence that the rate of reduction of the clinical picture and the likelihood of scarring ulcers and eradication rates higher in patients slow metabolizers of omeprazole. PMID- 26281175 TI - [FECAL NONINVASIVE TESTS (CALPROTECTIN, TRANSFERRIN, HEMOGLOBIN) IN COMPLEX DIAGNOSIS OF DISEASES OF INTESTINES]. AB - A research objective was the assessment of informational content of fecal noninvasive tests (calprotectin, transferrin, hemoglobin) in complex diagnosis of diseases of intestines. Open kogortny research by method of a cross cut included 52 patients (middle age - 38,6 years) with IBS-like symptoms (abdominal pain or discomfort, change of frequency and/or character of a chair). Sensitivity of dough on calprotectin for diagnosis of organic pathology of intestines made (89%), for dough on calprotectin and hemoglobin - also 89%. At patients at incomplete compliance of clinical signs to diagnostic criteria of IBS and lack of endoscopic signs of damage of a large intestine research on fecal biomarkers allows to increase efficiency of diagnostics. PMID- 26281176 TI - [ALLELES C282Y AND H63D HFE GENE, INSULIN RESISTANCE AND SUSCEPTIBILITY TO DISTURBANCE OF PORPHYRIN METABOLISM IN NON-ALCOHOLIC FATTY LIVER DISEASE]. AB - THE PURPOSE OF THE STUDY: The aim of the present work was to study the frequency of genotypes and alleles of C282Y and H63D HFE gene that may be associated with impaired porphyrin metabolism, as well as possible reasons for the formation of dysmetabolism porphyrins with NAFLD. MATERIALS AND METHODS: The study involved 65 patients (52 men and 13 women) aged 21 to 69 years (mean age 48.5+/-1.5 years). Excretion uroporphyrin, coproporphyrin, 6-aminolevulinic acid of porphobilinogen in urine was determined by chromatography and spectrophotometry calculated total excretion of porphyrins. Allele frequencies C282Y and H63D were determined during the molecular genetic analysis of DNA using the polymerase chain reaction followed by analysis of length polymorphism restraktsionnyh fragments. Condition of carbohydrate metabolism was evaluated by the level of fasting blood glucose and standard glucose tolerance test. Diagnosis of insulin resistance was performed according to the criteria proposed by the European Group for the Study of insulin resistance (EGIR). RESULTS: Skill test for the C282Y mutation carriage and H63D in the HFE gene in 65 patients with non-alcoholic fatty liver disease. Disturbances in the metabolism of porphyrins were recorded in 43 (66.2%) patients. H63D and C282Y mutations were found in 18 (27.7%) patients, of whom 13 (72.2%) people with different options dismetabolism porphyrins and signs of insulin resistance. In 47 (72.3%) patients without mutations studied porphyrin metabolism disorders were detected in 30 (63.8 %), of which insulin resistance is registered only in 16 (34.0 %). CONCLUSION: Detection of mutations C282Y and H63D in the HFE gene in combination with disorders of porphyrin metabolism on the background of insulin resistance is likely to allow such patients considered as candidates for inclusion in the higher risk of formation of diabetes. PMID- 26281178 TI - [CLINICAL EFFICACY AND SAFETY OF LITHOLYTIC THERAPY WITH LIVODEXA IN PATIENTS WITH CHRONIC CHOLECYSTITIS AND BILIARY SLUDGE]. AB - The authors present their own experience litholytic therapy of 68 patients with chronic cholecystitis and biliary sludge using the Livodexa (Sun Pharmaceutical Industries Ltd, India) at 12 and 24-week course of treatment. In a prospective 24 week investigation was estimated decrease in biliary sludge in the gallbladder as an integral indicator of the effective ness of litholytic therapy and decline of adverse event during treatment, as an indicator of the safety of treatment. PMID- 26281177 TI - [IMMUNOGENETICS AND PROGRESSION OF CHRONIC VIRAL HEPATITES]. AB - AIM OF INVESTIGATION: To estimate the role of polymorphic variants of genes IL4 (C-590T), IL4RA (I50V), TNF (G-308A) and SLC1IAI (D543N) in chronic viral hepatitis progression. MATERIAL AND METHODS: Overall 121 patients with chronic viral hepatitis C and B. RESULTS: Study results have demonstrated, that of all investigated polymorphic variants of genes IL4 (C-590T), IL4RA (150V), TNF (G 308A) and SLC11A1 (D543N) in patients with chronic liver diseases of various etiology the <> IL4RA gene variant (II50Val) is associated with HBV infection chronization. The allele <> gene TNF-alpha (G-308A) is protective for chronic viral hepatitis and is associated with a low level of production by mononuclear cells of TNF-alpha and IL-12, high secretion of IL-4 and low degree of collagenopathy in the liver. Genotype <> of IL4 (C-590T) gene is an adverse marker for progression of chronic viral hepatitis B. There was significant correlation of polymorphic variants TNF (G-308A) and IL4 (C-590T) genes with production of the key interleukins, that determine type of immune response (Th-1, Th-2) and products of collagen metabolism that testifies genetic determination of system immune response and collagen formation processes in the liver at chronic viral hepatitis. PMID- 26281179 TI - [CLINICAL AND ECONOMIC ANALYSIS OF ALTERNATIVE SCHEMES OF ANTIVIRAL THERAPY OF CHRONIC HEPATITIS C GENOTYPE 1 IN PATIENTS WHO DID NOT ANSWER TO THE PRIOR THERAPY, IN THE RUSSIAN FEDERATION]. AB - We conducted clinical and economic analysis of the protease inhibitor simeprevir versus currently available in Russia protease inhibitors (boceprevir and telaprevir) in combination with pegylated interferon and ribavirin and dual therapy with pegylated interferon and ribavirin in patients with chronic hepatitis C genotype 1 without polymorphism Q80K, who had not responded to previous treatment. Global cost-effectiveness model was adapted to the Russian health care system. We calculated differences in direct medical costs between the antiviral therapy schemes, treatment of long-term complications of chronic hepatitis C and the costs of achieving sustained virological response (SVR) to treatment. The incremental cost-effectiveness ratio - additional cost per life year saved was calculated as well. Available published data and the tariffs of the Russian healthcare system were used for the calculations. Simeprevir was shown to be more effective than dual therapy with acceptable additional costs and more effective than boceprevir and telaprevir in the number of life years saved being less costly therapy option. PMID- 26281180 TI - [ISCHEMIC REPERFUSION INJURY OF HEPATOCYTES IN THE PRESERVATION OF THE LIVER TRANSPLANT]. AB - This review is dedicated to one of the problems of liver transplantation and how to solve it. The incidence of complications after liver transplantation depends on ischemia-reperfusion injury of the graft. The global shortage of donor organs, using different technologies for conservation and graft function. This article describes the basic pathogenesis and proposed a new method for the prevention of ischemia reperfusion injury of the liver. PMID- 26281181 TI - [MODERN METHODS OF PHYSICAL-CHEMICAL RESEARCH IN GASTROENTEROLOGY PRACTICE: THE EXPERIENCE OF INTERACTION]. AB - The aim of this work was to assess the potential of some physical and chemical methods for studying erythrocytes and blood serum in gastroenterological practice by the example of colorectal cancer (CC). MATERIALS AND METHODS: A total of 26 persons with various stages of colorectal cancer and 16 healthy (control group) were examined. Parameters of erythrocytes and blood serum were investigated by light microscopy, dielectrophoresis in a non-uniform alternating electric field (DEF in NUAEF), terahertz spectroscopy, ellipsometry, Raman-spectroscopy. RESULTS: Polymorphism of erythrocytes, rigidity, viscosity, indexes of aggregation and destruction were significantly higher in patients with CC and polarizability, amplitude of erythrocyte deformation in NUAEF being lower than those in the controls. The study of erythrocytes by terahertz spectroscopy revealed the low levels of amplitude transmittance over the whole frequency range in CC patients compared to the controls. The increasing of refractive index, degree of heterogeneity of thin films obtained from the serum in CC patients were observed in considering the ellipsometric parameters. We found a significant increasing of the concentration of antigens to CD24 at the early stage of the disease. The areas of some peaks in Raman spectra were significantly lower in patients with CC compared to the healthy ones, it is possible due to a carotin deficiency. Most of the studied parameters were correlated with the stage of the disease. A set of optical methods for studying blood serum compared with those of histology and radiological methods of diagnosis showed their high sensitivity and specificity, positive and negative predictive value (80 % and above). CONCLUSION: The obtained results of the pilot study demonstrate the prospects of using physical and chemical methods of research of erythrocytes and blood serum for early diagnosis, stage of disease and monitoring the effectiveness of treatment of CC. PMID- 26281182 TI - [GASTROENTEROLOGICAL SYMPTOM IN DIABETES MELLITUS TYPE 2]. AB - The data of the literature and own data on the frequency and mechanisms of gastrointestinal symptoms in patients with diabetes mellitus type 2 are discussed. Changes in the gastrointestinal tract with diabetes mellitus type 2 are detected over its entire length and occur more frequently than in the general population. Among the reasons of it the presence of autonomic neuropathy, factor of hyperglycemia, increased anxiety and depression in patients are discussed. PMID- 26281183 TI - [CHANGES IN THE ORGANS AND TISSUES OF THE ORAL CAVITY WITH DIGESTIVE SYSTEM DISEASES]. AB - A substantial part of the pathology of organs and tissues of the oral cavity make common manifestations or systemic diseases. Accordingly, the dosage systemic therapy of these diseases can affect the condition of the eye. Changes in organs and tissues of the oral cavity and the appropriate advice a dentist can help the gastroenterologist in the diagnosis and adequate treatment of the patient. The article discusses possible changes in the organs and tissues of the oral cavity in diseases of the digestive system, as well as changes occurring under the influence of drug therapy of these diseases. PMID- 26281184 TI - [ABOUT PERSONALIZED MEDICINE AND STRATEGIES FOR ACTIVE LONGEVITY]. AB - The article gives a broad overview of the factors of cancer, presents biopsychosocial model of development of oncological diseases. The Program of medical and psychosocial care to patients with cancer with positions of personalized medicine was proposed. PMID- 26281185 TI - [MICROSCOPIC COLITIS: THE CLINICAL CASE]. AB - During past years incidence and prevalence of microscopic colitis (MC) have increased, that is possible caused to the improvement of knowledge of doctors about the disease. This article contain modern views on epidemiology, diagnostic and variant of microscopic colitis treatment. A typical clinical picture of MC in the form of recurrent a watery diarrhea, with the absence of pathologic changes at roentgenologic and endoscopic investigations is described with the example of a clinical case. PMID- 26281186 TI - [CLINICAL CASE OF CROHN'S DISEASE: A DIFFICULT PATH TO DIAGNOSIS]. AB - This article presents a case of Crohn's disease in a man who was veracity of 30 years from the onset of the disease. This case demonstrating complexity of diagnostic search, even with the classic version of the disease. And it demonstrates the need for a thorough medical history, differential diagnosis. PMID- 26281187 TI - [THE OUTBOUND PLENARY SESSION OF GASTROENTEROLOGICAL SCIENTIFIC SOCIETY OF RUSSIA "DISEASES OF THE DIGESTIVE ORGANS IN THE 21ST CENTURY: A MULTIDISCIPLINARY APPROACH. GASTROENTEROLOGY IN THE AGE ASPECT" SARATOV, RUSSIA 12-13 FEBRUARY 2015]. PMID- 26281188 TI - [Acute glomerulonephritis in the 21-st century]. AB - The paper discusses the specific features of the current course of acute glomerulonephritis, the spectrum of its etiological factors, and clinical manifestations. The factors influencing the course and outcomes of acute glomerulonephritis, including the risk of its progression to chronic kidney disease, are specially depicted. PMID- 26281190 TI - [Cystatin C is a new marker for left ventricular hypertrophy in patients with chronic kidney disease]. AB - AIM: To estimate the diagnostic value of serum cystatin C in the development of left ventricular hypertrophy (LVH) in patients with chronic kidney disease (CKD). SUBJECTS AND METHODS: The investigation enrolled 86 patients (53% men, 47% women; mean age, 45 +/- 13 years) with nondiabetic CKD. According to the magnitude of glomerular filtration rate (GFR) decrease, the patents were divided into 3 groups: 1) 33 patients with a GFR of 89-45 ml/min; 2) 33 with a GFR of 15 ml/min; 3) 20 hemodialysis patients with a GFR of < 15 ml/min. A control group included 20 individuals with a GFR of > 90 ml/min. In all the patients, physical examination and transthoracic echocardiography were performed and serum cystatin C levels were measured. RESULTS: In Groups 1, 2, and 3, LVH was detected in 42.4, 63.6, and 80% of cases, respectively. It was not found in the control group. In these groups, serum cystatin C levels were 1489.49 +/- 520.76, 2533.13 +/- 621.66, 5166.02 +/- 1586.61, and 820.08 +/- 224.54 ng/ml, respectively. An association was found between cystatin C and LVH (p = 0.5; p < 0.001). The level of cystatin C was shown to predict the development of LVH with a sensitivity of 78% and a specificity of 62% for predialysis CKD patients. Multivariate analysis of left ventricular mass index (LVMI), E-velocity/A-velocity, (E/A) ratio, and hypertension showed that the cystatin C levels were independently correlated with LVMI only (p < 0.05; p = 0.3) in all the groups. CONCLUSION: Serum cystatin C levels may be regarded as an early LVH marker detectable in patients with the earliest stages of CKD. PMID- 26281189 TI - [Role of the morphogenetic proteins FGF-23 and Klotho and the glycoprotein sclerostin in the assessment of the risk of cardiovascular diseases and the prognosis of chronic kidney disease]. AB - AIM. To analyze changes in the serum concentrations of the morphogenetic proteins fibroblast growth factor 23 (FGF-23) and Klotho, as well as sclerostin, an osteocyte-secreted glycoprotein, in relation to the degree of hypertension, left ventricular (LV) hypertrophy, and arterial stiffness in patients with chronic kidney disease (CKD) at its different stages. SUBJECTS AND METHODS: Sixty-five patients (33 men and 32 women) aged 20-65 years, including 25 with chronic glomerulonephritis, 15 with tubulointerstitial nephritis, and 25 with hypertensive nephrosclerosis, were examined. A control group consisted of 15 healthy volunteers matched to the study group patients for age and gender. Serum FGF-23 concentrations and blood pressure (BP) were measured in the all subjects. Patients with BPs > 140/80 mm Hg underwent echocardiography, followed by determination of LV mass (LVM) and calculation of LVM index. Vascular circulation, pulse wave velocity, cardiac and vascular calcifications, and vascular functional properties were estimated. RESULTS: There was a strong direct Correlation between the serum concentration of FGF-23 and the stage of CKD and an inverse correlation between the levels of Klotho and sclerostin and the stage of CKD. As the glomerular filtration rate became lower, the concentration of FGF-23 increased and that of Klotho and sclerostin decreased just in Stage III CKD while hyperphosphatemia and elevated parathyroid hormone levels were noted in Stages IV V CKD. As CKD progressed, the serum concentrations of Klotho and sclerostin were inversely correlated with the levels of phosphorus and parathyroid hormone. The degree of blood pressure elevation correlated positively with serum FGF-23 concentrations and inversely with Klotho levels. There was no significant correlation of the level of sclerostin with the degree of BP increase. The direct correlation between higher FGF-23 level and higher VLM is most pronounced in hypertensive patients. There was a strong direct relationship between FGF-23 and Klotho levels and a strong inverse relationship between sclerostin levels and pulse wave velocity. Lower Klotho concentrations were associated with the detection rate of calcifications in the heart valves and large arteries (the abdominal aorta). The reduced serum levels of Klotho and sclerostin were also correlated with concentric LV remodeling. CONCLUSION: It was demonstrated that there was a clear link between increased serum FGF-23 and decreased Klotho concentration as CKD progressed, and that between arterial stiffness and calcification and myocardial remodelling regardless of traditional risk factors. More experimental and clinical studies are required to clarify the role of sclerostin in CKD. PMID- 26281192 TI - [Prognostic value of renal resistance index in estimating the progression of chronic kidney disease]. AB - AIM: To study a relationship between main renal and intraparenchymal renal arterial resistance indices (RIs) measured by Doppler ultrasonography and clinical and laboratory parameters and to determine their prognostic value in estimating the progression of chronic kidney disease (CKD). SUBJECTS AND METHODS: The investigation enrolled 53 CKD patients divided into groups: glomerular and interstitial diseases. Glomerular filtration rate (GFR) calculated using the CKD EPI formula, proteinuria (PU) severity, kidney sizes, renal parenchyma thickness, parenchyma/collecting index, and main and intrarenal vessel RIs were determined at the first hospitalization. The mean follow-up was 14 +/- 2.64 months. The rate of GFR decline was estimated at the rehospitalization. RESULTS: Main renal and intrarenal vessel RIs depend on patient age and pulse pressure. The RIs are associated with GFR and PU in the group of glomerular diseases and with kidney sizes and structure in that of interstitial diseases. The interlobar arterial RI is the most sensitive predictor for worsening renal function with a threshold of 0.65, which is comparable to the prognostic value of PU. CONCLUSION: The main renal and intrarenal vessel RIs may be considered as a predictor for worsening renal function. PMID- 26281191 TI - [Endogenous erythropoietin, acute kidney injury, and prognosis in patients with acute coronary syndrome]. AB - AIM: To investigate the prognostic value of serum endogenous erythropoietin (EPO) in patients with acute coronary syndrome (ACS), including that in the development of acute kidney injury (AKI). SUBJECTS AND METHODS: Eighty-four patients (46 men, 38 women; mean age 63 +/- 11 years) with ACS were examined. Twenty-one (25%) patents were diagnosed with ECG ST-segment elevation acute myocardial infarction (STSEAMI), 12 (14%) had ECG non-STSEAMI, and 51 (61%) had unstable angina. Thrombolytic therapy was performed in 10 (48%) patients with STSEAMI. The patients whom had not undergone coronarography were included in the investigation to exclude the nephrotoxic effect of X-ray contrast agents. RESULTS: AKI was observed in 7 of the patients with acute myocardial infarction and in only 1 of those with unstable angina. Four (5%) patients died during hospitalization. The EPO level of > 10.5 IU/ml predicted the development of AKI in the ACS patients with a sensitivity of 71% and a specificity of 67%. That of > 13.7 IU/ml was associated with hospital death in the ACS patients with a sensitivity of 100% and a specificity of 75% (AUC = 0.93%). CONCLUSION: High serum EPO levels in an ACS patent during his hospital stay may serve as a biomarker for a high risk for AKI and high death rates. PMID- 26281193 TI - [Urinary biomarkers for podocyte injury: Significance for evaluating the course and prognosis of chronic glomerulonephritis]. AB - AIM: To estimate the degree of podocyte injury in patients with different types of chronic glomerulonephritis (CGN) from the urinary level of podocyte markers and to determine the significance of these indicators as criteria for disease activity and prognosis. SUBJECTS AND METHODS: Seventy-three patients with CGN, including 20 with inactive nephritis (Group 1), 23 with obvious urological syndrome (Group 2), 30 with nephrotic syndrome (NS) (Group 3), among them there were 7 patients with severe NS and 7 with NS concurrent with acute nephritic syndrome, were examined. A control group consisted of 8 healthy individuals. In the examined groups, the degree of podocyturia (PCU) was investigated by flow cytometry using podocalyxin-labeled antibodies and the levels of nephrinuria (NU), heat shock protein 27 (HSP27) in urine, interleukin 6 (IL-6), caspase 9, and vascular endothelial growth factor (VEGF) were estimated by ELISA. RESULTS: The patients with active CGN were found to have a high level of markers for podocyte injury: PCU and NU, which correlate with the magnitude of proteinuria, severity of NS, and degree of podocytopenia. Those with the severest NS, that concurrent with renal dysfunction in particular, were observed to have a progressive imbalance of inflammatory (IL-6), apoptotic (caspase-9), and defensive (HSP27 and VEGF) factors, which displays the incompetence of self defense mechanisms in podocytes and contributes to the torpid course of CGN. Progressive PCU and NU are a poor prognostic sign indicating the risk of glomerulonephritis. CONCLUSION: The indicators considered are universal for all patients with CGN running with proteinuria and may be used to monitor the course of the disease; moreover, the damaging factors should be considered in conjunction with the defensive factors. PMID- 26281194 TI - [Impact of interleukin-10 and interleukin-28 gene polymorphisms on the development and course of lupus nephritis]. AB - AIM: To assess the relationship of the carriage of IL-10-1080 G/A and IL-28 rs8099917 C/T polymorphisms to the course of lupus nephritis (LN). SUBJECTS AND METHODS: Ninety-nine patients with systemic lupus erythematosus (SLE), including 68 with LN, were examined. Gene polymorphisms were analyzed using standard molecular genetic techniques. The frequency of the clinical manifestations of LN was analyzed; renal survival (RS) was estimated by the Kaplan-Meier method. RESULTS: Ten-year RS rates were 80 and 86% of the patients with and without the mutant IL-10 allele, respectively (p = 0.78). The 10-year RS was lower (75%) in carriers of the mutant IL-28 rsl2979860 allele than in patients without this mutant allele (83%; p = 0.049) and in those of the mutant IL28 rs8099917 allele than in patients without the above mutant allele (67 and 88%, respectively; p = 0.047). LN patients, carriers of the mutant IL-10-1028 G/A allele, were observed to have higher-grade proteinuria in the presence of nephritic syndrome (mean 6.1 g/l) than those without the mutant allele of this gene (mean 2.9 g/l; p = 0.034). However, the mutant allele carriers responded to treatment better (p = 0.050). The mutant IL-10 and IL-28 alleles were unassociated with the development of rapidly progressive nephritis, the activity of a renal lupus process, and the rate of onset of SLE and LN. CONCLUSION: In the LN patients, the carriage of the mutant IL-10 allele A is associated with a better response to treatment and that of the mutant IL-28 allele is linked to the severe course of the disease. PMID- 26281195 TI - [Increased serum concentrations of inflammatory cytokines in type 2 diabetic patients with chronic kidney disease]. AB - AIM: To study the relationship between serum inflammatory cytokine levels in chronic kidney disease patients with type 2 diabetes. SUBJECTS AND METHODS: Sixty four patients aged 43 to 70 years with a glomerular filtration rate (GFR) of > 30 ml/min/1.73 m2 were examined. A control group consisted of 15 healthy individuals. The serum concentration of macrophage colony-stimulating factor (M CSF), macrophage inflammatory protein 1alpha (MIP-1alpha), macrophage migration inhibitory factor (MIF), interleukin 6 (IL-6), as well as the urinary excretion of albumin and type IV collagen was determined by enzyme immunoassay. RESULTS: In patients with a GFR of > 60 ml/min/1.73 m2, M-CSF and MIF concentrations proved to be significantly higher than those in the control group (p = 0.0003 and p = 0.001, respectively). In those with a GFR of 30-59 ml/min/1.73 m2, there was an increase in the levels of M-CSF (p < 0.0001), MIP-1alpha (p = 0.002), MIF (p = 0.02), and IL-6 (p = 0.02). The decline in GFR was associated with the higher levels of M-CSF (p = 0.02) and MIP-1alpha (p = 0.02) and with the higher urinary excretion of type IV collagen (p = 0.01). M-CSF, MIP-1alpha, and IL-6 correlated positively with the urinary excretion of albumin (r = 0.34, r = 0.28, and r = 0.28, respectively; all p < 0.05) and type IV collagen (r = 0.31, r = 0.4, and r = 0.43, respectively; all p < 0.05). CONCLUSION: The findings confirm the concept that chronic inflammation is involved in the development of diabetic kidney disease. PMID- 26281196 TI - [Contrast-induced acute kidney injury after primary percutaneous coronary interventions: Prevalence, predictive factors, and outcomes]. AB - AIM: To study the incidence, severity, predictive factors, and prognostic value of contrast-induced acute kidney injury (CIAKI) in patients with ST-segment elevation acute coronary syndrome (STSEACS), who have undergone primary percutaneous coronary intervention (PCI). SUBJECTS AND METHODS: The 2012 KDIGO criteria were used to estimate the incidence of CIAKI in 216 patients (mean age, 64 +/- 13 years) admitted to Moscow City Clinical Hospital Sixty-Four and underwent primary PCI for STSEACS (hypertension in 90%, prior myocardial infarction in 27%, chronic kidney disease in 7%, type 2 diabetes mellitus in 21%). Logistic regression analysis was performed to identify predictive factors for CIAKI; following 12 months, its prognosis was assessed by phone. RESULTS: Forty-three (20%) patients were diagnosed with Stages I (81%) and II (19%) CIAKI. The patients with CIAKI were older; they had higher baseline serum creatinine levels, a higher volume of contrast agent, a higher ratio of contrast medium volume to glomerular filtration rate, and lower left ventricular ejection fraction. Independent predictive factors for CIAKI were identified; these were chronic kidney disease, multivascular injury in the coronary bed, hospital therapy with loop diuretics, nephrotoxic antibiotics, or mineralocorticoid receptor antagonists. CONCLUSION: The development of CIAKI is associated with poor outcomes, such as higher 30-day mortality and more frequent cardiovascular disease readmissions. PMID- 26281197 TI - [Hemodynamic effects of succinate-containing dialyzing solution]. AB - AIM: To assess the results of using an acetate-free succinate-containing dialyzing solution (SDS) against natremia and blood pressure (BP) in patients on chronic hemodialysis (HD). SUBJECTS AND METHODS: Ninety-two patients were transferred from 3 Saint Petersburg HD centers to 3-month HD treatment using SDS. The investigators measured blood biochemical indicators immediately before and 1 and 3 months after the investigation, BP before and after a successive HD session, and the patients' weight and its gain in the period between HD sessions. Hypotensive and hypertensive episodes were recorded during HD sessions throughout the investigation. RESULTS: Following 3-month treatment using SDS, there were statistically significant decreases in blood sodium levels and systolic BP (SBP) prior to a HD session. At the same time, patients with a baseline pre-HD SBP of less than 100 mm Hg were observed to have a statistically significant increase in this indicator by the end of the investigation. Pre-dialysis diastolic BP (DBP) and post- dialysis SBP and DBP substantially unchanged. After 3 months of SDS use, there was a statistically significant reduction in weight gain in the period between HD sessions. When SDS was administered, the frequency of hypertensive episodes tended to decline after a HD session. CONCLUSION: The use of SDS causes a drop in pre-dialysis blood sodium levels, ensuring adequate dehydration in patients and improving hypertension control. In doing so, SDS prevents hypotension during a HD session. PMID- 26281198 TI - [Use of the Charlson comorbidity index and the Barthel disability index in the integrated assessment of the sociomedical status of patients receiving continuous renal replacement therapy with hemodialysis]. AB - AIM: To make an integrated assessment of the sociomedical status of patients receiving continuous renal replacement therapy (RRT) with hemodialysis (HD), by using the Charlson comorbidity index (CCI) and the Barthel disability index (BI) and to analyze the compliance of these indices with the disability severity estimated according to disability group (DG). SUBJECTS AND METHODS: The medical records of 605 HD patients (323 men, 282 women) whose mean age was 56.4 +/- 13.9 years and mean RRT duration was 65.6 +/- 62.8 months, were analyzed. The patients were grouped according to DG, CCI, BI, employment, and a history of diabetes mellitus. Data on basic laboratory parameters were collected. RESULTS: According to DG, the patients were grouped as follows: 1) 292 (51%); 2) 212 (37%); 3) 15 (3%) and 4) 48 (9%) without DG. The disability severity estimated according to DG was found to be correlated with RRT duration (r = -0.35; p < 0.001) and employment (r = 0.36; p < 0.001). CCI averaged 6.3 +/- 3.1 scores (n = 486). The mean BI was 86 +/- 14 scores (n = 224). Among the respondents completing the BI questionnaire, 26 (20%) patients with DG 1 showed an uncomplicated comorbid background (CCI, 2-5 scores), no significant disability (BI, 90-100 scores), while 33 (48%) patients with DG 2 exhibited a high comorbidity index (ICC, more than 5 scores) and obvious disability (BI, less than 90 scores). The indicators relating to restricted self-movement in some BI scales were of the most importance. CONCLUSION: The disability severity estimated in view of DG does not correspond to the severity of comorbidities (CCI) and the magnitude of functional limitations (BI) in some patients with CKD 5D. While determining DG, it is advisable to take into account CCI as an indicator of the severity of physical disorders to objectify the estimate of the sociomedical status of patients with CKD 5D, as well as BI to determine the degree of disability. PMID- 26281199 TI - [Fibroblast growth factor 23 and a novel high-sensitivity troponin I: Early markers and alternative ways of damaging the heart in chronic kidney disease]. AB - AIM: To establish possible pathogenetic relationships between the marker of bone mineral metabolism fibroblast growth factor 23 (FGF-23) and the markers of cardiovascular diseases characterizing the state of cardiomyocytes and that of the vascular wall of the aorta and large vessels in chronic kidney disease (CKD). SUBJECTS AND METHODS: A total of 110 patients (57 men and 53 women) aged 25 to 65 years (mean age 56 +/- 2.2 years) with different stages of CKD were examined. FGF 23 and troponin I in the sera from all the patients were investigated using enzyme immunoassay kits. Doppler echocardiography was carried out to evaluate the morphofunctional state of the left ventricle (LV). Peak systolic blood flow velocity in the aortic arch and common carotid intima-media thickness were estimated to assess the wall of the aorta and large arteries. RESULTS: As renal failure progressed, just at the early CKD stages the patients were found to have elevating FGF-23 and troponin I levels forestalling an increase in parathyroid hormone concentrations and changes in other calcium-phosphorus metabolism indicators. The levels of FGF-23 and the morphofunctional indicators of LV lesion showed a strong direct correlation that preserved its significance in analyzing the factors under study in relation to the function of the kidneys. CONCLUSION: The morphogenetic protein FGF-23 seems to play a significant role not only in bone remodeling processes, but also in the development of cardiovascular events in CKD. However, the mechanisms of its implication in the development of heart disease, like the possibilities of using its level changes as early diagnostic criteria for cardiovascular involvement, call for further investigation. PMID- 26281200 TI - [Urinary excretion of angiogenesis regulatory factors and renal injury markers in chronic glomerulonephritis: Significance in the assessment of progression]. AB - AIM: To study the urinary excretion of the molecular factors regulating angiogenesis, such as vascular endothelial growth factor type A (VEGF-A), thrombospondin 1 (THBS1), and angiopoietin 2 (ANGPT2), versus that of the urinary markers of renal injury and fibrogenesis, such as neutrophil gelatinase associated lipocalin (NGAL), type IV collagen (COL4), and known clinical risk factors for accelerated disease progression to estimate the prognostic value of urinary excretion in patients with chronic glomerulonephritis (CGN). SUBJECTS AND METHODS: Eighty-two patients (45% men, 55% women; mean age, 36.5 years) with a clinical diagnosis of CGN were examined. 31.7% of the examinees presented with nephrotic syndrome; 31.7% had a glomerular filtration rate (GFR) of less than 60 ml/min/1.73 m2. Morning urine samples were analyzed by Elisa to determine the urinary excretion of biomarkers (VEGF-A, THBS1, ANGPT2, NGAL, and COL4). The results were adjusted to urinary creatinine concentrations. RESULTS: The urinary excretion of the angiogenesis regulators VEGF-A, THBS1, and ANGPT2 correlated between them, with that of the renal injury markers NGAL and COL4, with the level of proteinuria. That was found to be unassociated with blood pressure and GFR. In the presence and absence of nephrotic syndrome, high (> 75th percentile) urinary excretion rates were 46.2 and 14.8% for VEGF-A (p < 0.01); 50 and 13% for THBS1 (p < 0.001); and 46.2 and 14.8% for ANGPT2 (p < 0.01), respectively. That for ANGPT2 was also high in the presence of anemia (63.2 versus 11.7%; p < 0.001). CONCLUSION: The finding of the high urinary excretion of the angiogenesis regulators VEGF-A, THBS1, and ANGPT2 and its association with that of kidney injury markers in the patients with the proteinuric forms of CGN suggest that this excretion may be considered as an integral index that displays glomerular injury and indicates tubulointerstitial proteinuric/hypoxic remodeling. PMID- 26281201 TI - [Efficiency of tacrolimus therapy for perianal Crohn's disease]. AB - AIM: To determine the efficacy of 0.1% tacrolimus ointment in patients with perianal Crohn's disease (CD). SUBJECTS AND METHODS: This prospective randomized trial enrolled 20 patients with perianal CD as anal fissures and rectal fistulas. The inclusion criteria were rectovaginal or extrasphincteric fistulas and purulent leakages. A study group comprised 11 patients, including 9 with anal fissures and 2 with fistulas. A control group included 9 patients, including 8 with fissures and 1 with fistulas. The study group received systemic therapy with azathioprine 2 mg/kg/day and tacrolimus ointment 2 mg/day; the control group had systemic therapy with azathioprine 2 mg/kg/day, hormone ointment 1 mg/day, and metronidazole suppositories 250 mg/day. Control examination and perianal CD activity index (PCDAI) determination were done 6 and 12 weeks after therapy initiation. RESULTS: At 6 weeks after beginning the study, local examination revealed the signs of anal fissure epithelialization in 5 (45.5%) of the 11 patients in the study group and in 3 (33.3%) of the 9 patients in the control one. At 12 weeks, fissure epithelialization and fistula obliteration were stated in 6 (54%) patients in the study group and in 3 (33%) of the 9 patients in the control group. At 12 weeks, PCDAI in the study and control groups was 2.00 and 4.44 scores (p = 0.01). CONCLUSION: The findings suggest that topical 0.1% tacrolimus ointment versus antibacterial suppositories and hormone ointments is effective in treating patients with perianal CD. Topical 0.1% tacrolimus ointment therapy caused a reduction in PCDAI. PMID- 26281202 TI - [Meta-analysis of clinical trials of cardiovascular effects of magnesium orotate]. AB - AIM: To make a meta-analysis of clinical trials of magnerot (magnesium orotate) used in cardiac patients. SUBJECTS AND METHODS: The meta-analysis covered the data of 19 randomized trials including a total of 603 patients treated with magnerot (a case group) and 587 receiving placebo (a control group). The patients' mean age was 36 +/- 19 years. On the average, the patients took magnerot 1878 +/- 823 mg/day for 4.2 +/- 29 months. RESULTS: Associations between the intake of magnerot and the risk of 50 pathological conditions were analyzed. Significant associations were established between the drug's administration and the reduced risk of conditions, such as hypomagnesemia (relative risk (RR) = 0.06; 95% confidence intervals (C): 0.04 to 0.09; p = 2 . 10(-46)), exercise intolerance (RR = 0.41; 95% CI: 0.27 to 0.62; p = 0.0004), dysautonomia (RR = 0.08; 95% CI: 0.04 to 0.14; p = 2 . 10(-21)), morning headache (RR = 0.16; 95% CI: 0.09 to 0.29; p = 1.5-10(-6)), tension headache (RR = 0.16; 95% Cl: 0.09 to 0.27; p = 5 . 10(-10)), dizziness (RR = 0.28; 95% CI: 0.15 to 0.50; p = 0.0004), first-degree mitral valve prolapse (MVP) (RR = 0.05; 95% CI: 0.03 to 0.09; p = 1.2 . 10(-25)), grade 1 regurgitation (RR = 0.29; 95 CI: 0.14 to 0.60; p = 0.0075), supraventricular (RR = 0.30; 95% CI: 0.21 to 0.44; p = 1 . 10(-8)) and ventricular (RR = 0.48; 95% CI: 0.30 to 0.76; p = 0.019) premature contraction, paroxysmal supraventricular tachycardia (RR = 0.28; 95% CI: 0.15 to 0.50; p = 0.0002), and hypertension (RR = 0.32; 95% CI: 0.17 to 0.58; p = 0.0027). CONCLUSION: The use of magnesium orotate is promising not only in treating MVP and compensating for hypomagnesemia, but also in preventing and treating cardiac arrhythmias, regulating blood pressure, and improving the function of the autonomic nervous system. PMID- 26281203 TI - [The concurrence of light-chain deposition disease, AL-amyloidosis, and cast nephropathy in a patient with multiple myeloma]. AB - Despite of the fact that their clinical manifestations are similar, AL amyloidosis (AL-A) and light chain deposition disease (LCDD) are individual nosological entities in view of considerable differences in their pathogenesis and pathomorphology. The paper describes a rare case of the concurrence of LCDD and AL-A in a patient with multiple myeloma. Clinically, there was dialysis dependent renal failure, flail leg syndrome, myocardiopathy, and rhabdomyolysis. At the disease onset, his nephrobiopsy specimen could diagnose LCDD and myeloma or cast nephropathy. The disease was characterized by an aggressive course. Despite the administration of innovative agents, the patient had a short-term remission and died from disease progression. Autopsy additionally revealed amyloid deposition in the heart and kidney. The development of AL-A in the presence of prior LCDD may reflect the progression of the tumor and the appearance of an additional subclone of plasma cells that produce amyloidogenic light chains. The uncommonness of this case is that renal amyloid was found in the tubular casts and absent in the glomeruli, which may be considered as a special form--tubular AL-amyloidosis. PMID- 26281204 TI - [Algorithm for the diagnosis, treatment, and prevention of stress (for general practitioners)]. AB - By inducing physical and mental disorders, human stresses are known to lead to long-term serious consequences and frequent use of more medical resources. Owing to long-term clinical trials, a management algorithm based on the principles of personalized medicine has been elaborated to minimize the consequences of stress, to activate natural adaptation mechanisms and to enhance stress resistance. PMID- 26281205 TI - [Kidney injury associated with monoclonal gammopathies: Perspectives on diagnosis and treatment]. AB - It is currently well justified that monoclonal gammopathies are the most important predictor for kidney diseases, including glomerulonephritis. To determine a correlation of nephropathy with oligosecretory gammopathy is of fundamental importance, as the treatment of these patients necessitates the use of special chemotherapy regimens to eliminate a pathological clone of lymphocytes or plasmocytes. If this clone is not eliminated, injury of the organ may recur to develop its failure. The principles of this therapy have been presently tried out by the example of AL-amyloidosis and showed its efficiency and relatively low toxicity. PMID- 26281206 TI - [Cryoglobulinemic vasculitis with renal involvement: A historic aspect of the problem]. AB - The paper presents the steps for studying cryoglobulinemia from essential to cryoglobulinemic vasculitis associated with hepatitis C virus. It shows advances in the study of the etiology of cryoglobulinemia, diagnosis, specific features of renal injury, and current approaches to treating HCV infection-related cryoglobulinemic vasculitis with renal involvement, by using 3 clinical cases (with a difference of a few decades during a follow-up). PMID- 26281207 TI - [PHENOTYPIC CHARACTERIZATION AND FUNCTIONAL FEATURES OF MEMORY T- AND B-CELLS]. AB - In this review, we systematized the data that characterize phenotypic properties and functional features of T- and B-lymphocytes of immune memory. We examin the organization of T-cells of immune memory in a population, and their selective distribution in the organism according to their effector potential. PMID- 26281208 TI - [ON THE PLURALITY OF THE WAYS OF RADIATION ADAPTIVE RESPONSE FORMATION IN HUMAN PERIPHERAL BLOOD LYMPHOCYTES]. AB - The current review summarizes the results of investigations on the phenomenon of the decrease of cell radiosensitivity after the impact of various damaging factors in small doses. This phenomenon is known as an adaptive response (AR). It has been described in a number of biological objects, but the author has reviewed only the researches that have been done on human peripheral blood lymphocytes. Lymphocyte AR is specifically characterized by the fact that the entire cascade of events that decrease radiosensitivity occurs during one mitotic cycle. This feature distinguishes lymphocyte AR from the phenomenon of cell adaptation to chronic small dose irradiation. In this review, the author pays special attention to research on the initial stages of the AR formation. The author presumes that the AR occurs as a result of nonspecific intracellular changes that are a signal of the disruption in cell homeostasis. Several researchers define the state that results from this as the state of stress. After a cell transfers to this state there is a launch of biochemical processes that are able to protect the cell in case of future exposure to large doses of damaging factors (including irradiation). These processes are not determined strictly by the initial stimulus and are not initiated directly by the impact of the external factor that induced the AR. The particular method of decreasing radiosensitivity has not been determined and its selection depends on cell genotype, conditions of the experiment, etc. This might be the synthesis of various types of reparation enzymes, the synthesis of antioxidant enzymes, the activation of cell division or apoptosis. Cells that do not turn into the stress state do not form an AR. If there is no damaging shock-like impact after the cell enters the stress, the cell gets back to the normal rest state and the ability to form an AR disappears. PMID- 26281209 TI - [DNA CONTENT IN INDIVIDUAL CHROMOSOMES OF NORMAL CHINESE HAMSTER KARYOTYPE AND CHROMOSOMES OF CONSTANT HAMSTER CELL LINES CHL V-79 RJK AND Vebr-5]. AB - Using cytometry and an microfluorimetry, we have determined the genome size in Chinese hamster Cricetulus griseus, as well as absolute and relative DNA content of its individual chromosomes and of chromosomes in the transformed Chinese hamster cell lines V-79 RJK and Vebr-5 after prolonged cultivation. It has been shown that the genome size in male and female Chinese hamster is 6.660 and 6.746 pg, respectively. Absolute content of chromosomal DNA of both studied cell lines differed significantly from the content of the corresponding chromosomal DNA of the Chinese hamster normal karyotype. During long-term cellular cultivation, changes in the DNA content of certain chromosomes in both cell lines (generally upward) reached 20-25 %. The level of DNA amplification in the p-arm of chromosome Z6, registered at the beginning of the experiment, in the course of further cellular cultivation (over 20 years) remained stable. The data obtained allow us to conclude that the malignant transformation of cells and subsequent adaptation to the conditions in vitro leads to a profound restructuring of its genome, which affects almost all chromosomes. PMID- 26281210 TI - [FEATURES OF tRNA GENES AND YOUNG SUBFAMILIES Alu-REPEATS EXPRESSION IN PROLIFERATION AND APOPTOSIS]. AB - Using human U937 cell culture, we studied the expression of the RNA polymerase III-directeci genes--tRNAi(Met)1, tRNA(His) and Alu-repeats belonging to the youngest subfamilies AluY (AluYa5 and AluYb8) - du- ring camptothecin-induced apoptosis. The level of tRNAiMetl increased 1.5-fold, tRNAHis level did not change, and the level of AluY-RNA increased 4-10-fold after 6 hours of CAM treatment compared to control (non-apoptotic) cells. We also studied the level of AluYb8 DNA methylation at apoptosis U937. We have shown that the level of AluYb8 DNA methylation does not change at different stages of apoptosis, and does not differ in apoptotic and control cells. We assume that the increase in gene expression of young AluY repeats and tRNAi(Met)1 plays a role in the apoptosis pathway realization in the cell. PMID- 26281211 TI - [THE INDUCTION OF CD25 EXPRESSION IN Jurkat T CELLS]. AB - The expression of an alpha-subunit of interleukin-2 receptor (IL-2Ralpha) was assessed by quantifying activation-induced upregulation of CD25 in IL-2 independent Jurkat leukemic cell line. It has been found that in growing Jurkat culture within 24 h, phytohemagglutinin (PHA, 5 MUg/ml) or PHA in combination with 12,13-phorbol dibutirate (PDBu, 10(-8)M) increase the number of CD25+ cells to 32.3 +/- 3.4% (n = 11) and 44.8 +/- 8.6% (n = 6) respectively. Interleukin-2 (IL-2, 200 U/ml) alone or in combination with PDBu did not induce CD25 expression in Jurkat cells. All the tested stimulatory agencies affected neither the proliferation status no the growth of Jurkat cell cultures. In contrast to human blood T cells, WHI-P131, a selective pharmacological inhibitor of JAK/STAT signaling and CD25 expression, did not decrease the number of induced CD25+ cells in Jurkat culture. Flow cytometry analysis revealed a dose-dependent decrease in the proportion of cells in G1 phase and an increase in the proportion of cells in G2/M phase in WHI-P131-treated Jurkat cultures. It has been also found that WHI P131 induces G2/M arrest in the absence of PHA or PDBu. We have concluded that (1) the IL-2-independent T cells of Jurkat line had not loss the mechanism for IL 2Ralpha expression in response to T cell receptor activation, (2) in the transformed T cells, WHI-P131 can arrest cell cycle at G2/M phase and has effects on targets other than IL-2 receptor-associated tyrosine kinase JAK3. PMID- 26281212 TI - [LIGHT-DEPENDENT SYNTHESIS OF CELL MEMBRANES IN THE Brc-1 MUTANT OF CHLAMYDOMONAS REINHARDTII]. AB - The structural organization of cells of the Brc-1 mutant of the unicellular green algae Chlamydomonas reinhardtii grown in the light and in the dark has been studied. The Brc-1 mutant contains the brc-1 mutation in the nucleus gene LTS3. In the light, all membrane structures in mutant cells form normally and are well developed. In the dark under heterotrophic conditions, the mutant cells grew and divided well, however, all its cell membranes: plasmalemma, tonoplast, mitochondrial membranes, membranes of the nucleus shell and chloroplast, thylakoids, and the membranes of dictiosomes of the Golgi apparatus were not detected. In the dark under heterotrophic conditions, mutant cells well grow and divide. It were shown that a short-term (1-10 min) exposure of Brc-1 mutant cells to light leads to the restoration of all above-mentioned membrane structures. Possible reasons for the alterations of membrane structures are discussed. PMID- 26281214 TI - [SPREADING OF NCTC CLONE 929 CELLS AFTER RESEEDING]. AB - The period (1 h after reseeding) of behaviour of mouse NCTC clone 929 cells to the conditions of artificial cultivation was studied. The time-lapse imaging followed the processing of the cells with ImageJ program was applied. To characterize the parametres cell status we used the cell area (projection of the cell on substrate) and Rp/Ra ratio introduced earlier as a spreading coefficient (Kuz'minykh, Petrov, 2004). After attaching a substratum, cells have a form of sphere (the phase "sphere") as the daughter cells after a mitosis. We revealed however that after this phase the reseeded cells do not start usual spreading and migration along substratum. They pass a phase of equally spreading in all directions and shaping their area as a circle (phase "circle"). This phase is absent of the daughter cells spreading after mitosis. We assume that the phase "circle" is a result of adaptation of the cells to reseedings at artificial cultivation. It is necessary for formation of a substrate composed of own extracellular matrix components (ECM) of the cells. Own ECM facilitates transition of the cells to their usual spreading and migration along substratum. PMID- 26281213 TI - [THE EFFECTS OF LONG-TERM METFORMIN TREATMENT ON THE ACTIVITY OF ADENYLYL CYCLASE SYSTEM AND NO-SYNTHASES IN THE BRAIN AND THE MYOCARDIUM OF RATS WITH OBESITY]. AB - Biguanide metformin, which is widely used for the treatment of type 2 diabetes mellitus, improves carbohydrate and lipid metabolism and shows a pronounced cardio- and neuroprotective effects. It is assumed that an important role in these effects of metformin plays its ability to positively influence the activity of NO-synthase catalyzing the synthesis of NO, the most important vasodilator, and the activity of hormone-sensitive adenylyl cyclase signaling system (ACSS. To prove this, we have carried out a study whose purpose was to study the effect of long-term metformin treatment on the metabolic rates in obese rats, as well as on the activity of ACSS and NO-synthase in the myocardium and the brain of these animals. The metformin treatment of Wistar rats with obesity induced by high-fat diet was carried out for 2 months (daily dose of 200 mg/kg). The treatment with metformin led to a decrease in body weight and body fat, reduced glucose and insulin levels as well as reduced insulin resistance index HOMA-IR, improved glucose tolerance, and decreased the level of atherogenic forms of cholesterol. In the myocardium of obese rats, the attenuation of ACSS stimulation induced by the agonists of beta1/beta2-adrenergic receptors (AR) and the strengthening of beta3-AR signaling has been found. At the same time, in the myocardium of animals treated with metformin, the regulation of ACSS by adrenergic agonists was restored, and the ratio of beta-AR-signaling pathways returned to normal. In the brain of rats treated with metformin, adenylyl cyclase stimulating effects of serotonin and agonists of type 4 melanocortin receptors, which had been weakenend for obesity, were restored. Metformin treatment completely restored activity of total and endothelial NO-synthase in the myocardium decreased in obesity. It as also shown that metformin treatment induced hyperactivation of NO-synthase in the myocardium and brain of healthy animals. Thus, we conclude that the effects of metformin identified by us in rats with long-term treatment of obesity may explain cardio- and neuroprotective influence of this drug. PMID- 26281215 TI - [HISTOLOGYCAL AND HISTOCHEMICAL CHARACTERISTICS OF AREOLAE IN THE PIG PLACENTA]. AB - Rounded white lustreless dome-shaped wheels are detected by visually from allantochorion side in the in fetal areas epiteliochorial pig's placenta on day 30 of pregnancy. These structures are located over the opening of the uterine glands. Areolaes consist from maternal and foetal parts. Areola include glandular epithelium, chorial and endometrial stroma at the mouth of the uterine glands, areolar cavity-enhanced formed by endometrial and chorial invaginations. Chorion gives in cavity radial folds lining differences high epithelium. Glycogen, neutral and acid sulfated glycoproteins, proteoglycans, glycosaminoglycans, hyaluronates, total and cationic protein, RNA, arginine, gistidine, lysin were founded in structural components of areoles during gestation period. Numerous areolas serve as specialized sites for absorption the secrets of uterine glands; they are form a powerful functional system of histotrophic nutrition. PMID- 26281216 TI - [MOTION AFTEREFFECT AS A UNIVERSAL PHENOMENON IN SENSORY SYSTEMS INVOLVED IN SPACE ORIENTATION. II. AUDITORY MOTION AFTEREFFECT]. AB - Adaptation to sound source motion can cause noticeable changes in spatial perception of the following sound stimuli. Neural mechanisms of selective sensitivity to motion are the basis of this phenomenon, called the auditory motion aftereffect. The auditory motion aftereffects were demonstrated under different stimulation conditions, both after the presentation of different motion models and in the real sound source motion. The auditory aftereffects are specifically characterized by its spatial and frequency selectivity as well as by the optimal motion velocity at which the effect is maximal. These features and the presence of the intersensory motion adaptation effects indicate a common nature of the auditory and visual motion aftereffects and allow suggesting the existence of the common system of motion adaptation for different modalities that provide spatial orientation. PMID- 26281217 TI - [THE ROLE OF FOOD OBJECTS AND ENTERAL MICROBIOTA PROTEASES IN NUTRITIVE AND TEMPERATURE ADAPTATIONS OF THE DIGESTIVE SYSTEM IN FISH]. AB - The review presents data on the activity and some temperature characteristics of proteases in the potential food objects of fishes and some enteral microbiota representatives that provide induced autolysis and symbiotic digestion. It is shown that during the active feeding period the total protease activity in the prey tissues exceeds the total protease activity in the fish gastric mucosa by 5 10 times. At low temperature, the relative activity of the prey tissue lysosomal hydrolases (20-35%) and the enteral microbiota enzymes (up to 45%) may exceed that of proteases synthesized by the hepatopancreas and functioning in the consumers' intestinal mucosa (less than 10% maximal activity). The data presented indicate the important role of proteases of food objects and enteral microbiota in nutritive adaptations of the fish digestive system. PMID- 26281218 TI - [SENSITIVITY OF LIVER MONOAMINE OXIDASE IN THE LAMPREY LAMPETRA FLUVIATILIS TO SOME TRICYCLIC COMPOUNDS]. AB - A comparative analysis of the effect of the five acridine, three phenothiazine and one xanten (pyronine G) derivatives on the activity of liver mitochondrial monoamine oxidase (MAO) in sexually mature male river lampreys Lampetra fluviatilis has been conducted. Tyramine, dopamine, serotonin, noradrenaline, benzylamine, beta-phenylethylamine and N-methylhistamine have been used as substrates for analyzing the monoamine oxidase activity of heterocyclic compounds. The analyzed synthetic hexamerous tricyclic compounds exhibit irreversible inhibition of the enzyme but no specificity depending on the desaminated substrate. The number and identity of heteroatoms in the analyzed heterocyclic compounds have been established to influence their inhibitory efficiency. The data of substrate-inhibitory analysis obtained with the use of the specific substrates provide indirect evidence for the existence of a single MAO form in the lamprey liver. PMID- 26281219 TI - [BETA-ADRENERGIC REGULATION OF THE ADENYLYL CYCLASE SIGNALING SYSTEM IN MYOCARDIUM AND BRAIN OF RATS WITH OBESITY AND TYPES 2 DIABETES MELLITUS AND THE EFFECT OF LONG-TERM INTRANASAL INSULIN TREATMENT]. AB - The stimulating effect of norepinephrine, isoproterenol and selective beta adrenoceptor (beta3-AR) agonists BRL 37344 and CL 316.243 on the adenylyl cyclase signaling system (ACSS) in the brain and myocardium of young and mature rats (disease induction at 2 and 4 months, respectively) with experimental obesity and type 2 diabetes mellitus (DM2), and the influence of long-term treatment of animals with intranasal insulin (I-I) were studied. The AC stimulatory effects of beta-agonist isoproterenol in animals with obesity and DM2 was shown to be practically unchanged. The respective effects of norepinephrine on the AC activity were attenuated in the brain of young and mature rats and in the myocardium if mature rats, and the I-I treatment led to their partial recovery. In the brain and myocardium of mature rats with obesity and DM2, the enhancement of the AC stimulatory effects of beta3-AR agonists was observed, white in young rats the influence of the same pathological conditions was lacking. The I-I treatment decreased the AC stimulatory effects of beta3-agonists to their levels in the control. Since functional disruption of the adrenergic agonist-sensitive ACSS can lead to metabolic syndrome and DM2, the recovery of this system by the I I treatment offers one of the ways to correct these diseases and their complications in the nervous and cardiovascular systems. PMID- 26281220 TI - [MECHANISMS OF THE EFFECT OF Li+ ON MYOCARDIUM OF VERTEBRATES]. AB - The effect of Li+ on the frog Rana temporaria myocardium and its influence on the ion transport in the rat heart mitochondria (RHM) were studied. Li+ added to the normal Ringer solution (Li(+)-R) was found to attenuate myocardial tension, decrease the maximal rate of tension development and its half-relaxation time. Comparison of the cardiac muscle contraction parameters in the Li(+)-R with the effect of the voltage-gated Ca(2+)-channels (Cav1.2), verapamil and CdCl2, showed that the negative inotropic effect of the Na+ replacement by Li+ in the limited intermembrane ("fuzzy") space is underlain by the blocking of Ca2+ influx into the myoplasm via the reverse Ca2+/Na(+)-exchanger in the plasma membrane (PM). This, in turn, prevents Ca(2+)-induced massive Ca2+ release into the myoplasm via the RYR2-channels in the sarcoplasmic reticulum (SR) leading in aggregate to suppression of Ca(2+)-dependent myocardial contractions. In the experimental studies of the Li+ effect on the RHM it was established that Li+ just slightly increases the passive permeability of the inner mitochondrial membrane (IMM) for K+ and H+ and decreases the intensity of ion pumping out of the energized mitochondrial matrix to the external medium. This may also indicate the lack of relationship between the mitochondrial oxidative processes and the reduction in the myocardial contractile activity under the Na+ replacement by Li+. PMID- 26281221 TI - [THE EFFECT OF HYPOXIA ON THE DEVELOPMENT OF HONEY BEE WORKERS AT PREPUPAL AND PUPAL STAGES]. AB - The effect of different levels of hypoxia on viability, physiological condition and morphometric characters of the honey bee (Apis mellifera L.) workers at the prepupal and pupal stages was traced. A high tolerance of the honey bee brood to hypoxia was established. Excess CO2 by more than two orders of magnitude relative to its content in the atmosphere and beehive at the optimal temperature for a bee family exhibits a mimimum lethality. Morphological anomalies manifested as wing and proboscis hypoplasia were found at the CO2 concentration raised by 10-15 %. This leads to a reduction on the number of frenulum hooks on the hind wings and affects their asymmetry variability. The wing lengths and the number of frenulum books are in inverse while masses of the head, thorax and abdomen--in direct relationship with the CO2 concentration. PMID- 26281222 TI - [PLASTICITY OF THE THERMAL REACTION NORMS FOR DEVELOPMENT IN THE EUROPEAN PEACOCK BUTTERLY INACHIS IO (LEPIDOPTERA, NYMPHALIDAE)]. AB - The goal of this study was to examine the plasticity of the thermal reaction norms for development in the European Peacock butterfly Inachis io under the effect of different photoperiodic conditions and group versus individual maintenance. The overwintered imagoes were collected in Old Peterhof (near Saint Petersburg) in May, 2010 and 2012-2013. 12 experimental regimens were used: 4 temperatures (16, 18, 20 and 22 degrees C) and 3 photoperiods (12, 18 and 22 h of light a day). It was found that under short-day conditions (12 h) the caterpillars developed a little faster than under long-day ones (22 h). The developmental temperature thresholds in these two cases did not differ. A linear regression coefficient characterizing thermal sensitivity of development was significantly higher only in males with their development affected by short-day photoperiod stronger than in females. At 18-h day length, the caterpillar development was less temperature-sensitive and characterized by a lower threshold than in shorter and longer days. The influence of short-day photoperiod on the caterpillar development manifested itself most distinctly in the emerging pupae' weight changes: in all the temperature regimens the pupae were lighter at short than at long days. The pupal weight increased as the temperature rose. The found dependence does not agree with the "temperature-size rule". Individual rearing led to a longer duration and lower thermal sensitivity of caterpillar and pupal development as well as to a reduced weight of the pupae. Individual rearing had a stronger impact on the mineral of females than males. PMID- 26281223 TI - [COMPARATIVE STUDY OF NIGROSTRIATAL SYSTEMS IN WISTAR RATS AND RATS PRONE TO SEIZURES]. AB - In this work we analyzed the levels of functional activity of dopaminergic, GABA ergic and glutamatergic neurons in the nigrostriatal system of control Wistar rats and Krushinsky-Molodkina (KM) rats prone to audiogenic seizures. In KM rats we have revealed disturbed activity of GABA- and dopaminergic neurons in substania nigra whereas the level of glutamatergic neurotransmission remained unchanged. We have also observed no significant differences in GAD65/67 and phospho-tyrosine hydroxylase contents in the striatum of KM and control Wistar rats. However, a high level of D1 dopamine receptor and a decreased level of D2 receptor found can mediate the upregulation of glutamatergic neurotransmission. Indeed, the expression of vesicular glutamate transporter type 2 (VGlut2) and NR2B subunit of NMDA receptor was increased in the striatum of KM rats. In striatal glutamatergic fibers phosphorylated ERK1/2 kinases have been revealed; at the same time, in KM rats an increased ERK1/2 activity has been detected both in striatum and substantia nigra. This finding correlated with activation of exocytosis rate as evidenced by downregulation of SNAP25 level. Apart from other reasons, the activation of glutamatergic system may be a result of disruption of the inhibitory effect of the dopamine- and GABAergic systems of substantia nigra that innervate striatum. We suppose that the increased activity of striatal glutamatergic neurons of KM rats without an adequate inhibition by GABA- and dopaminergic systems may be one of the reasons of high convulsive susceptibility in KM rats. PMID- 26281224 TI - [APPLICATION OF FLOW CYTOMETRY FOR THE ANALYSIS OF CIRCULATING HEMOCYTE POPULATIONS IN THE ASCIDIAN HALOCYNTHIA AURANTIUM (PALLAS, 1787)]. AB - This study addresses the potentialities of flow cytometry in analyzing the composition of circulating hemocyte populations in the ascidian Halocynthia aurantium (Pallas, 1787) both using monoclonal antibodies (mAbs) against some human leukocyte conservative adhesion molecules and without mAbs. Flow cytometry, based on the assessment of forward and side scattering revealed five hemocyte populations. From the wide panel of antibodies against human leukocyte adhesion molecules (CD15, CD29, CD34, CD54, CD62L, CD62P, CD90, CD94, CD117, CD 166), only two mAbs (against CD54, CD90) displayed cross-reactivity with the H. aurantium hemocyte surface antigens. Distribution patterns of these antigens across the hemocyte populations have been analyzed. PMID- 26281225 TI - [COMPARATIVE ANALYSIS OF THE FLUORESCENT PROTEIN REABSORPTION IN FROG AND RAT KIDNEYS]. PMID- 26281226 TI - [General and Specific Mechanisms of Visual Cognitive Function Impairment in People with FMRP Deficit]. AB - The purpose of this article is to provide the overview of visual cognitive development in subjects with FMRP deficit. Description of fragile X mental retardation syndrome is presented in the article, that is the most common cause of inherited intellectual disability and one of the most prevalent genetic causes of autism spectrum disorder. The syndrome is associated with deficit of fragile X mental retardation protein following FMR1-gene mutation. Researches of static and dynamic object perception, face perception and oculomotor control are discussed in the article. The results obtained by subjects with FX syndrome are compared with ASD data, syndrome with closed behavioral phenotype. Several factors that underlie visual cognitive deficit are discussed in the article. PMID- 26281227 TI - [Stem Cells in the Brain of Mammals and Human: Fundamental and Applied Aspects]. AB - Brain stem cells represent an extremely intriguing phenomenon. The aim of our review is to present an integrity vision of their role in the brain of mammals and humans, and their clinical perspectives. Over last two decades, investigations of biology of the neural stem cells produced significant changes in general knowledge about the processes of development and functioning of the brain. Researches on the cellular and molecular mechanisms of NSC differentiation and behavior led to new understanding of their involvement in learning and memory. In the regenerative medicine, original therapeutic approaches to neurodegenerative brain diseases have been elaborated due to fundamental achievements in this field. They are based on specific regenerative potential of neural stem cells and progenitor cells, which possess the ability to replace dead cells and express crucially significant biologically active factors that are missing in the pathological brain. For the needs of cell substitution therapy in the neural diseases, adequate methods of maintaining stem cells in culture and their differentiation into different types of neurons and glial cells, have been developed currently. The success of modern cellular technologies has significantly expanded the range of cells used for cell therapy. The near future may bring new perspective and distinct progress in brain cell therapy due to optimizing the cells types most promising for medical needs. PMID- 26281228 TI - [The Influence of Long-Term Meditation Practice on Early Emotional Processing in the Brain: an ERP Study]. AB - The main aim was to study effects of long-term meditation practice on event related brain potentials (ERPs) during affective picture viewing. The meditators' (N = 20), contrary to control (N = 20), did not demonstrate arousal-related increases in the mid-latency (200-400 ms) ERP positivity over the right hemisphere. We also found in the same time window stronger ERP negativity for meditators over central regions, regardless of picture valence. We assume that long-term meditation practice enhances frontal top-down control over fast automatic detection of stimulus salience. PMID- 26281229 TI - [Complex Neurophysiological Examination of Patients with Affective Disorders]. AB - In order to find objective physiological correlates of affective disorders we have carried out the complex examination of patients comparing with the control group. Psychophysiological tests, EEG and speech signal parameters have shown statistically significant difference between the groups. At clinical practice our conclusions might be used on the diagnostics stage. PMID- 26281230 TI - [Association between the 5-HTTLPR Polymorphism of Serotonin Transporter Gene and EEG in Young and Postmenopausal Women]. AB - Effect of ovarian steroids on serotonin neurotransmission suggests that the modulating effect of polymorphisms of the serotonin transporter gene on brain activity in women may change with age related changes in hormonal status. Objective of the study was to identify relationships between 5-HTTLPR polymorphism of the serotonin transporter gene and characteristics of baseline EEG in healthy young women (19-35 years, N = 85) and in women in post menopause (55-80 years, N = 44). It was shown that in S'/S'(SA/SA, SA/LG) and L'/L' (LA/LA) genotypes carriers' women of the older age group had lower delta, alpha 2 and alpha 3 band power than the young. In older women genetic differences in the power of these rhythms were due to lower values in carriers of S'/S' and L'/L' compared with S'/L' genotype. S'/L' genotype was characterized by higher beta 1 rhythm power in elderly compared with young women. These results demonstrate the difference in the neurophysiological mechanisms of age-related changes in brain activity which are associated with the polymorphism of 5-HTTLPR. PMID- 26281231 TI - [Macroscopic Functional Networks of the Human Brain when Viewing and Recalling Short Videos]. AB - Macroscopic functional network of the human brain were identified by use of the independent component analysis (ICA) of fMRI while viewing and imaging/recalling stories. The networks were relatively stable in structure, but had a specific dynamics in different experimental conditions. When comparing detected networks with previously detected resting state networks it was found that they coincide on localization. We. discovered also the specificity of activating the peripheral and central parts of retinotopic projections in the visual cortex. The peripheral areas were activated during subject viewing and imaging/recalling. On the contrary, the central departments strengthened their activation when viewing and reduced activity during the imaging/recalling. PMID- 26281232 TI - [Vulnerability to Depression and Oscillatory Resting-State Networks]. AB - Depression is the most commonly observed mood disorder, which is accompanied by changes in emotional processes and the default mode network (DMN) activity. In this study, we aimed to investigate how predisposition to depression shows up in the emotional coloring of spontaneous thoughts and the activity of oscillatory resting-state networks, as revealed by source localization and independent component analysis techniques. Depressive symptoms correlated positively with the prevalence of negative emotion during EEG registration and with delta and theta activity in the orbitofrontal cortex and negatively with theta activity in the DMN. Since an increase of low-frequency oscillations in the orbitofrontal cortex is observed in aversive states, whereas their decrease in the DMN reflects an activation of this network, which is related to self-referenced processing, our results are consistent with the notion that vulnerability to depression is associated with general negative emotional disposition and excessive focus on the self. PMID- 26281233 TI - [How Sound Modulates Response to Light when Using Various Temporal Intervals between Stimuli of Different Modalities]. AB - Extracellular activity of 34 primary visual cortex neurons of the rabbit was recorded in response to audiovisual stimulation with stimulus onset asynchronies (SOA) in range from -750 to + 150 ms (15 ranges in total). Auditory stimulus: 2000 Hz, 70 dB, 40 ms. Visual stimuli: two weak intensities 0.3 and 1 cd/m2. Sound by itself did not elicit a neuronal response. Factor analysis ANOVA revealed that SOA significantly influence on neuronal responses. Neuronal reaction included responses to increase (on-response) and decrease (off-response) of light intensity. Earliest phase of response (40-100 ms from visual stimuli substitution) is most affected by sound. Neuronal reactions of the every interval of SOA comprised both increase and decrease of discharge in response to addition of a sound. We used a Wilcoxon signed-rank test to show the differences between reactions in response to visual and audio-visual stimuli. Audio-visual on responses statistically exceeded the responses to visual stimuli at -150, -40 and 0 ms SOA for the all neurons. Two groups of neurons were revealed. The first group (n = 16) showed dependence of on-re- sponses on sound in a wide range of SOA: -150, -40, -20, 0, +20, +50 and +100 ms. Also the first group showed maximum increase of spike number (18-28%) in response to audio-visual stimulation. For the second group of neurons there were no significant SOA for on-responses. We haven't found a significant decrease of audio-visual response compared to a visual response. However, we found the tendency to reduction of audio-visual discharge at intervals SOA -750 and -80 ms (p < 0.07) for the first group and at SOA -500 and +20 ms (p < 0.1) for the second group of neurons. Also we revealed that on-responses are more influenced by sound than off-responses. We have researched the audio-visual interaction in the second phase of neuronal discharges (120-160 ms and later, n = 23). Sound influence on a second phase is weaker than on a first phase. Significant SOA for on-responses: 0 ms; for off responses: +100 and +150 ms. This study has revealed similarities of audio-visual interaction range for animal and psychophysical researches. Our results allows. to research cross-modal integration in more detail. PMID- 26281234 TI - [Delta-, theta-Modulation of the Ventral Tegmental Area Fast-Gamma Activity in the Course of Performance of Conditioned Avoidance Reflex in Rat]. AB - The prestimulus expectation period of conditioned avoidance reflex features synchronized Delta-rhythm (1-4 Hz) in the medial prefrontal cortex and the ventral tegmental area (VTA), and synchronized theta-rhythm (6-8 Hz) in the above mentioned structures and the hippocampus. According to "Granger causality" Delta- and theta-rhythms flow (are predictors) in the direction from the prefrontal cortex and the hippocampus to the VTA. Performance of conditioned avoidance reflex was marked by Delta-rhythm elimination simultaneously with generation of high-frequency (8-11 Hz) synchronized theta-rhythm. Delta-rhythm was shifted from the pre- to poststimulus period and prefrontal cortex--VTA theta-synchrony was eliminated in the cases of mistaken reaction withdrawal, Pavlovian fear conditioning scheme, conditioned signal presentation in the safe chamber part. The phase of Delta-, theta-rhythm modulates the amplitude of VTA fast (70-160 Hz) gamma-activity envelope, VTA/cortex and VTA/hippocampus gamma-phase synchronization and phase lag indexes, and frequency of simultaneously recorded VTA neuronal activity. PMID- 26281235 TI - [Nitrergic Activity of the Medial Prefrontal Cortex in Rats with High and Low Conditioned Fear Generalization]. AB - For Sprague-Dawley rats by means of in vivo microdialysis combined with HPLC analysis it was shown that an acquisition of a conditioned fear response (paired presentation of an auditory conditioned stimulus (CS+) and unescapable footshock) caused the increase in extracellular levels of citrulline (an NO co-product) in the medial prefrontal cortex which was almost completely prevented by local infusions of 1 mM NOmega-propil-L-arginine, a neuronal NO synthase inhibitor and was not observed in control rats. The magnitude of this increase was high in rats showing later low freezing to conditioned stimulus previously not paired with footshock (CS-) and it was low in rats characterized by high freezing to CS-, but it did not interfere with freezing to the conditioned stimulus CS+ previously paired with footshock. The data obtained indicate for the first time that the conditioned fear acquisition is accompanied by nitrergic activation within the medial prefrontal cortex which is associated with conditioned fear generalization but not with conditioned fear expression. PMID- 26281236 TI - Expert History and the Tribulations of Trials. PMID- 26281237 TI - Bridging Troubled Waters: Historians, Natural Resource Litigation, and the Expert Witness Phenomenon. AB - This special issue of The Public Historian examines the nature and scope of the historian's role as a consultant and expert witness in natural resource litigation. The introductory essay identifies the major issues and challenges that historians face when they bring their knowledge, skills, and professional best standards into law offices and courtrooms, while also positing a conceptual framework for public history practitioners to better understand and appreciate the larger stakes in conducting research for environmental litigation. The author delineates his own experience as an expert in certain water rights cases in the American Southwest where knowledge of the Spanish and Mexican civil law of property is essential. PMID- 26281238 TI - The Advocate's Devil: The Maritime Public Historian as Expert Witness. AB - The maritime historian working as litigation support and expert witness faces many challenges, including identifying and analyzing case law associated with admiralty subjects, cultural resource management law, and general historical topics. The importance of the unique knowledge of the historian in the maritime context is demonstrated by a case study of attempts to salvage the shipwreck Atlantic, the remains of a merchant vessel built and enrolled in the United States and lost in the Canadian waters of Lake Erie in 1852. PMID- 26281239 TI - Bury My Documents in Lenexa, Kansas: Expert Witness Work and the American Indian Records Repository. AB - Restricted access to the American Indian Records Repository (AIRR) poses significant problems for expert witness historians working outside the federal government, as well as for academic historians and tribes. The authors discuss the creation of the AIRR in 2004, the records housed there, and the challenges they have experienced as expert witnesses seeking access to the AIRR. Although the AIRR preserves a far greater volume of federal records than might have otherwise occurred, the lack of public access may ultimately impede historians' ability to examine modern topics in Native American history and United States tribal relations. PMID- 26281240 TI - Why Litigation-Driven History Matters: Lessons Learned from the Secret History of TCE. AB - Litigation drives extensive historical research but often allows only select observers to see the results. Historians have conducted untold studies for litigation that become "secret histories" because these histories are not published. An example is the historical use and regulation of the chemical trichloroethylene (TCE), a hazardous chemical at issue in much environmental litigation, but a topic virtually absent in the secondary literature. This practice seems to contravene accepted standards of open scholarship. Although not directly aligned with the traditional academic model of historical practice, however, historical research and writing for litigation achieve legitimate and important results without abandoning the discipline's professional standards. History done by consultants for litigation is neither a history of compromised standards nor as "secret" as feared. PMID- 26281241 TI - Indigenous Space and the Landscape of Settlement: A Historian as Expert Witness. AB - This essay examines my work as expert witness in the case of U.S. v. Michigan, a Indigenous use-rights case. I was charged with parsing the intention of a specific article of the 1836 Treaty of Washington compelling land cession by Anishinaabe peoples and with writing a history of land use in the area from that date to the present for the Chippewa Ottawa Resource Authority (my employer). The challenges were not only methodological (how do you estimate use from ownership?) and epistemological (what constitutes proof that will satisfy both historians and lawyers?), but also sociological and psychological: what happens when an associate professor puts her progress toward full professor on hold for the sake of a court case? PMID- 26281242 TI - From Archive to Evidence: Historians and Natural Resource Litigation. AB - Within the field of natural resource law are several specific areas that are well suited for the historian's skillset and knowledge. The deployment of the historian's tool box when conducting research in the legal world, however, can result in deliverables which vary significantly from those found in the academy, as they range widely in both size and scope and do not always use the full range of a historian's skills. New technological platforms provide consulting historians with creative opportunities to disseminate valuable information and sources and enhance important scholarly debates. PMID- 26281243 TI - Documentary Evidence and the Construction of Narratives in Legal and Historical Contexts. AB - Based on her experiences as an expert witness in Canadian litigation related to Aboriginal peoples, the author shares some personal reflections on the use of the written record as "evidence" in a legal context. As end users in a litigation context will be constructing their own narratives, a historian can add value in the courtroom by sharing skills in analyzing and providing context for written materials as well as providing a narrative based on their content. This process of simultaneously constructing and deconstructing a narrative can support the legitimacy of multiple narratives and provide space for evidence of other types, particularly oral evidence. PMID- 26281244 TI - The Pragmatic Roots of Public History Education in the United States. PMID- 26281245 TI - [Modern concepts of trauma care and multiple trauma management in oral and maxillofacial region]. AB - Multiple trauma management requires the application of modem trauma care theories. Optimal treatment results can be achieved by reinforcing cooperation and stipulating a treatment plan together with other disciplines. Based on modem theories in trauma care and our understanding of the theoretical points, this paper analyzes the injury assessment strategies and methods in oral and maxillofacial multiple trauma management. Moreover, this paper discusses operating time and other influencing factors as well as proposed definitive surgical timing and indications in comprehensive management of oral and maxillofacial multiple trauma patients associated with injuries in other body parts. We hope that this paper can help stomatological physicians deepen their understanding of modem trauma care theories and improve their capacity and results in the treatment of oral and maxillofacial multiple trauma. PMID- 26281246 TI - [The study of the colorimetric characteristics of the cobalt-chrome alloys abutments covered by four different all-ceramic crowns by using dental spectrophotometer]. AB - OBJECTIVE: This study aims to evaluate the optical data of the different sites of the cobalt-chrome (Co-Cr) alloy abutments covered by four different all-ceramic crowns and the color difference between the crowns and target tab using a digital dental spectrophotometer. METHODS: Ten Co-Cr alloy abutments were made and tried in four different groups of all-ceramic crowns, namely, Procera aluminia, Procera zirconia, Lava zirconia (Lava-Zir), and IPS E.max glass-ceramic lithium disilicate-reinforced monolithic. The color data of the cervical, body, and incisal sites of the samples were recorded and analyzed by dental spectrophotometer. The CIE L*, a*, b* values were again measured after veneering. The color difference between the abutments covered by all-ceramic crowns and A2 dentine shade tab was evaluated. RESULTS: The L* and b* values of the abutments can be increased by all of the four groups of all-ceramic copings, but a* values were decreased in most groups. A statistical difference was observed among four groups. After being veneered, the L* values of all the copings declined slightly, and the values of a*, b* increased significantly. When compared with A2 dentine shade tab, the DeltaE of the crowns was below 4. CONCLUSION: Four ceramic copings were demonstrated to promote the lightness and hue of the alloy abutments effecttively. Though the colorimetric baseline of these copings was uneven, veneer porcelain can efficiently decrease the color difference between the samples and thee target. PMID- 26281247 TI - [Comparison of magnetic resonance imaging artifacts of five common dental materials]. AB - OBJECTIVE: To compare five materials commonly used in dentistry, including three types of metals and two types of ceramics, by using different sequences of three magnetic resonance imaging (MRI) field strengths (0.35, 1.5, and 3.0 T). METHODS: Three types of metals and two types of ceramics that were fabricated into the same size and thickness as an incisor crown were placed in a plastic tank filled with saline. The crowns were scanned using an magnetic resonance (MR) machine at 0.35, 1.5, and 3.0 T field strengths. The TlWI and T2WI images were obtained. The differences of various materials in different artifacts of field MR scans were determined. RESULTS: The zirconia crown presented no significant artifacts when scanned under the three types of MRI field strengths. The artifacts of casting ceramic were minimal. All dental precious metal alloys, nickel-chromium alloy dental porcelain, and cobalt-chromium ceramic alloy showed varying degrees of artifacts under the three MRI field strengths. CONCLUSION: Zirconia and casting ceramics present almost no or faint artifacts. By contrast, precious metal alloys, nickel-chromium alloy dental porcelain and cobalt-chromium ceramic alloy display MRI artifacts. The artifact area increase with increasing magnetic field. PMID- 26281248 TI - [Experimental study on the effects of the nerve growth factor regulating calcitonin gene-related peptide in promoting the proliferation of MG-63 in vitro]. AB - OBJECTIVE: To investigate the nerve growth factor (NGF) regulating the expression of calcitonin gene-related peptide (CGRP) in promoting the proliferation of osteoblast-like cell (MG-63) and thus illustrate the mechanism of the NGF in wound healing. METHODS: Different concentrations of NGF were used to stimulate MG 63. The expression of CGRP was detected by real-time quantitative polymerase chain reaction (RT-QPCR) and enzyme-linked immunosorbent assay after 1, 2, 3, and 4 days. The proliferation of MG-63 was detected by cell counting kit-8 (CCK-8). The expression of CGRP mRNA and the proliferation of MG-63 were then detected by RT-QPCR and CCK-8 after adding the NGF receptor blocker. RESULTS: Compared with the blank control group, the expression of CGRP significantly increased by stimulating the NGF. The expression of CGRP was positively related to the concentration of NGF (P<0.05). Moreover, the expression of CGRP increased by prolonging the NGF stimulation time. The proliferation of MG-63 increased after stimulating the NGF (P<0.05). After adding the NGF receptor blocker, the expression of CGRP and the proliferation of MG-63 correspondingly decreased (P<0.05). CONCLUSION: NGF can up-regulate the expression of CGRP and increase the proliferation of MG-63. Therefore, NGF plays a significant role in wound healing. PMID- 26281249 TI - [Culturing and characterization of human gingival mesenchymal stem cells and their chemotactic responses to stromal cell-derived factor-1]. AB - OBJECTIVE: To investigate the expression of chemokine stromal cell-derived factor 1 (SDF-1) receptor CXCR4 in human gingival mesenchymal stem cells (GMSCs) and the migration potential of GMSCs stimulated with SDF-1. METHODS: Human GMSCs were isolated by single-cell cloning method. Their cell surface markers were characterized by flow cytometry, and the rate of colony formation was evaluated. Differentiation assay was used to detect the differentiation potential of GMSCs. The expression of chemokine SDF-l receptor CXCR4 in GMSCs was detected by immunocytochemical staining. The chemotactic effect of SDF-1 on GMSCs was detected using a 24-multiwell Transwell cell culture chamber. The number of net migrated cells was counted in different microscope fields. RESULTS: Human GMSCs possessed high self-renewal potential and formed single-cell colonies cultured in vitro. GMSCs expressed mesenchymal stem cells-associated markers CD44, CD73, CD90, CD105, and CD166, and the expression of hemopoietic stem cell surface markers CD14, CD34, and CD45 was negative. GMSCs differentiated into osteoblasts and adipocytes under defined culture conditions. The colony forming unit fibroblastic for GMSCs was 21.4%/+/-2.8%. Immunocytochemical staining demonstrated that GMSCs expressed chemokine SDF-1 receptor CXCR4. The number of GMSCs migrating at concentrations of 100 ng.mL-1 and 200 ng.mL-1 of SDF-l in the Transwell cell culture chamber was significantly higher than that of the negative control (189.3+/-4.4, 164.6+/-4.9 cells/field vs. 47.8+/-2.5 cells/field, P<0.01). Treatment with the CXCR4 neutralizing antibody, an antagonist for CXCR4, significantly reduced the migratory effect compared with the negative controls (29.0+/-2.4 cells/field vs. 47.8+/-2.5 cells/field, P<0.01). CONCLUSION: Human GMSCs express chemokine SDF-l receptor CXCR4. SDF-1 may participate in regulating chemotaxis of human GMSCs. Results suggest that the migration induced by SDF-1 is mediated by CXCR4. PMID- 26281250 TI - [Immunoexpression and clinical significance of interleukin-21 and receptor activator of nuclear factor kappaB ligand in human periapical granulomas and radicular cysts]. AB - OBJECTIVE: This study aimed to detect the immunoexpression of interleukin-21 (IL 21) and receptor activator. of nuclear factor KB ligand (RANKL) in periapical granulomas (PGs) and radicular cysts (RCs). The interaction of IL-21 with RANKL and its role in periapical pathogenesis were also speculated. METHODS: A total of 32 PGs and 23 RCs were selected as experimental samples. Lesion size and occurrence of tenderness were recorded. Up to 10 healthy gingival tissues were collected as normal control samples. All tissues were subjected to immunohistocheincal analysis with anti-human IL-21 and RANKL polyclonal antibodies. The correlations of IL-21 with RANKL, lesion size, and the occurrence of tenderness of the PGs and RCs were evaluated. RESULTS: IL-21-positive cells were detected in all periapical lesion tissues but not in normal tissues. In the cyst group and granuloma group, the corresponding expression levels of IL-21 were 59.92+/-6.57 and 36.80+/- 6.81, whereas those of RANKL were 68.81+/-18.59 and 36.12+/-14.87, respectively. Moreover, t-test revealed a significantly higher expression of IL-21 and RANKL in RCs than in PGs (P<0.05). IL-21 and RANKL were positively correlated in both PGs and RCs (P<0.05). Furthermore, IL-21 was correlated with lesion size (P<0.05). CONCLUSION: This study demonstrated that IL 21 is potentially involved in the pathogenesis of apical periodontitis lesions. A role in the exacerbation of chronic inflammation, as well as in bone resorption, is suspected. Further studies are required to elucidate the specific functions of IL-21 in periradicular inflammatory processes. PMID- 26281251 TI - [Interleukin-23 strengthens the anti-apoptotic and drug resistance of human tongue squamous cell carcinoma through the Wingless-related integration site/beta catenin pathway]. AB - OBJECTIVE: This study aims to detect the expression level of interleukin-23 (IL 23) in tongue squamous cell carcinoma tissues and its relationship with clinical prognosis, as well as explore the anti-apoptotic and drug resistance of the tongue squamous cell line-SCC9 before and after treatment with IL-23. METHODS: The expression of IL-23 in tumor tissues from 28 tongue cancer patients was analyzed by immunohistochemistry assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression of Wingless-related integration site (Wnt)1 and c-myc in SCC9 cells treated with different IL-23 concentrations. After interferencing the beta-catenin with small interfering RNA (siRNA), the expression of beta-catenin, B-cell lymphoma-2 (Bcl-2), ATP-binding cassette sub-family G member 2 (ABCG2), and permeability-glycoprotein (P-gp) in SCC9 was measured by Western blot analysis. The effect of IL-23 on the apoptotic resistance of SCC9 to cisplatin was examined by methyl thiazolyl tetrazolium test. RESULTS: The expression of IL-23 in tongue cancer tissues was correlated with lymphatic metastasis, nerve invasion, and the recurrence after therapy (P<0.05). After dealing with IL-23, SCC9 showed the upregulation effect of Bcl-2, ABCG2 and P-gp expressions. IL-23 was closely related to the activation level of the Wnt pathway and significantly strengthened the resistance to cisplatin (P<0.01). CONCLUSION: IL-23 activates the Wnt pathway in tongue squamous cell carcinoma, thereby enhancing its resistance to apoptosis and drug. PMID- 26281252 TI - [Integrated assessment of middle ear dysfunction in cleft palate patients and optimization of therapeutic schedule]. AB - OBJECTIVE: To explore evaluation strategies for middle ear dysfunction in cleft palate patients, to optimize the diagnosis and treatment of this dysfunction, and ultimately to improve the comprehensive treatment of cleft palate. METHODS: The relationship among abnormal tympanic types (B, C, and Anomaly), effusion rate, tympanic pressure, and hearing loss were analyzed. We collected relevant information on 469 ears of cleft palate patients and traced one-year longitudinal changes in the tympana of 124 ears from 62 patients with both cleft lip and cleft palate. RESULTS: The effusion rates of cleft palate patients with type B, type C, and type Anomaly were 50.3% (97/193), 34.8% (8/23), and 20.9% (53/253), respectively. The tympanic pressure of the ears with and without effusion showed no significant difference (P>0.05). The hearing loss in type B cleft palate patients with middle ear effusion was worse than that in patients without effusion (P=0.001). However, the hearing loss in type Anomaly showed no difference (P>0.05). The constituent ratio of each tympanic type remained constant during the period between cheiloplasty and palatoplasty for cleft lip and palate patients (P>0.05). CONCLUSION: Cleft palate patients of all tympanic types may all suffer from middle ear effusion at different rates. Examination by centesis is suggested for ears with abnormal tympanic types. Early aggressive therapy is essential for type B cleft palate patients with middle ear effusion to avoid hearing loss. However, catheterization may be not necessary for type Anomaly patients, and conservative observation should be performed instead. Myringotomy with grommet insertion during palatoplasty does not delay treatment timing for patients with both cleft lip and cleft palateg. PMID- 26281253 TI - [Clinical comparative study on the treatment characteristics of secretory otitis media between cleft and non-cleft palate patients]. AB - OBJECTIVE: To discuss the treatment characteristics of secretory otitis media (SOM) in cleft palate children. METHODS: A total of 319 patients (524 ears) with SOM and cleft palate (3-14 years old) who accepted treatment were divided into experiment group A, group B, and group C according to effusion characteristics in the middle ear and tympanic pressure. Group A included 112 patients with serous effusion (198 ears). Group B included 162 patients with mucinous effusion (248 ears). Group C included 45 patients (78 ears) with negative pressure in the middle ear without effusion and an acoustic immittance. A total of 208 patients (246 ears) with SOM and tonsil and adenoid hypertrophy were divided into control group Al, group B1, and group Cl matched with the same effusion characteristics in the middle ear and tympanic pressure. Group A and Al accepted puncture in the tympanic cavity, group B and B1 accepted tympanostomy tubes, and group C and Cl accepted puncture in the tympanic cavity after palatoplasty, adenoidectomy, and tonsillectomy. All groups were treated with antibiotics and ear drops. Cure rate and recurrence rate between the experiment group and the control group were compared. RESULTS: The control group had a better cure rate [93.09% (229/246)] than the experiment group [77.29% (405/524)] 12 months after treatment. The experiment group had a higher recurrence rate [14.57% (59/405)] than the control group [3.93% (9/229)]. Statistical differences were observed between the two groups (P<0.05). SOM with cleft palate initially had a low cure rate, and thus it was treated repeatedly for many times. CONCLUSION: SOM with cleft palate is different from normal otitis media in terms of clinical manifestation, treatment, outcome, and prognosis. This case should be considered a special otitis media to be treated with special examination and therapy to obtain better results. Repeated puncture in the tympanic cavity and tympanostomy tubes for six months according to effusion characteristics are better treatment options for patients with SOM and cleft palate. PMID- 26281254 TI - [Three years retrospective clinical evaluation of endodontically treated premolars restored by cast ceramic onlays]. AB - OBJECTIVE: This study aimed to evaluate the success and survival rate of endodontically treated premolars restored by ceramic onlays by comparing restored by quartz fiber posts and metal ceramic crowns. METHODS: Ninety-four patients with 126 endodontically treated premolars were enrolled in this study and divided into 4 groups according to the remaining axial walls and restorative methods. The observation time was 36 months. The success and survival rates of the restorations, as well as causes of failures, were analyzed. RESULTS: At the final follow-up, the success and survival rates of the mild defect endodontically treated premolars were restored by quartz fiber posts and the crowns were at 96.3% and 98.1%; the success and survival rates of the severe defect premolars restored by quartz fiber posts and crowns were at 88.5% and 96.2%. The success and survival rates of the mild defect premolars restored by cast ceramic onlays were both at 96.6%, the success and survival rates of the severe defect premolars restored by cast ceramic onlays were at 94.1% and 100%, respectively. The success and survival rates of the different groups were no significant difference (P>0.05). CONCLUSION: Based on the results and within the limits of this study, cast ceramic onlays is a very reliable method to restore endodontically treated premolars. PMID- 26281255 TI - [Stability of the anterior teeth and hard tissue of skeletal class III malocclusion after orthodontic surgery: systematic review]. AB - OBJECTIVE: This study aims to analyze the long-term stability of the anterior teeth and hard tissue of skeletal class III malocclusion after a three-year orthodontic surgery by systematic review. METHODS: All studies about skeletal class III malocclusion with orthodontic-surgery were searched by computer-based retrieval and manual retrieval; the deadline is December 2013. The literature, filtered according to the inclusion criteria and exclusion criteria, was performed with quality. assessment. The same indicators of the anterior location and hard tissue stability were combined and evaluated with metaanalysis and descriptive analysis by Rev Man5.2. RESULTS: Four before-and-after comparison study articles with 180 cases were included. The grades of the four literature evaluation were A. The meta-analysis results showed that comparing the three-year post-orthodontic-surgery and post-orthodontic-surgery, the total weighted mean difference (WMD) of Ul-SN was 4.29 (P<0.05); the WMD of Ll-MP, OB, OJ, SNA, SNB, ANB, and MP-SN were -1.58, 0, -0.41, -0.58, 0.25, -0.70, and 0.39, respectively (P>0.05). The measurement methods of A and B point position were different, hence the qualitative description were as follows: point A remained at a relatively stable position, and point B had some replacement compared with post-operative (P<0.05). CONCLUSION: To the skeletal class III malocclusion after three-year orthodontic-surgery, the position of the lower anterior teeth could be kept stable, as well as the overbite and the overjet of the anterior teeth; only the upper inci- sor has a lip-inclined relapse. The maxillary could also be kept stable, and the mandibular had a little relapse. PMID- 26281256 TI - [Reconstruction of the orbital fracture with enophthalmos using customized titanium mesh combined with Medpor]. AB - OBJECTIVE: This study aims to evaluate the effect of customized titanium mesh, which was designed by mirror imaging and rapid prototyping technique, with Medpor applied for orbital fracture with enophthalmos. METHODS: Orbital axial, coronal, and sagittal CT scan, and three-dimension CT examination were performed routinely in. 18 cases of orbital fracture with enophthalmos preoperatively. Based on the CT data, prosthesis model was designed by reverse engineering and rapid prototyping technique. The customized titanium mesh and Medpor were applied for orbital reconstruction and enophthalmos correction. Orbital reduction and globe projection were evaluated by postoperative CT scan and clinical follow-up visits. RESULTS: CT scans revealed that the customized titanium mesh with Medpor had great accuracy to reconstruct the orbital fracture and correct the enophthalmos in all patients without serious complications. The eye and facial appearance and function recovered significantly. No serious complication occurred in the operation and after operation. CONCLUSION: The customized titanium mesh, based on mirror imaging and rapid prototyping technique, can accurately reconstruct the orbital fractures with enophthalmos. The application of Medpor can effectively correct enophthalmos and eyeball mobility malformation. PMID- 26281257 TI - [Chimeric deep circumflex iliac artery perforator flap for the simultaneous reconstruction of the composite oromandibular defect]. AB - OBJECTIVE: To evaluate the feasibility and outcomes of chimeric deep circumflex iliac artery perforator flap (DCIAPF) applied in the simultaneous reconstruction of the oromandibular defect. METHODS: Six patients underwent simultaneous oromandibular reconstruction using DCIAPF following segmental mandibulectomy in Xiangya Hospital from March 2014 to July 2014. The skin paddle was designed to be centered on the pre-operative perforator mapping. Retrograde dissection was performed through the underlying abdominal wall to raise the skin paddle. The pedicle was isolated from the groin, and the iliac crest was cut. The deep iliac circumflex vessels were dissected until the skin paddle was reached. Finally, the donor site was strictly sutured layer by layer to avoid ventral hernia. RESULTS: The skin paddles ranged from 3.5 cmx5.0 cm to 7.0 cmx 10.0 cm. The length of the bone components was 5.0 cm to 11.0 cm. All donor sites closed primarily without skin grafting. DCIAPF was harvested successfully in five patients, except for one patient whose perforator originated from the superficial iliac circumflex vessels. An additional pair of anastomoses was performed. All iliac flaps survived. However, slight skin-edge necrosis and exfoliation caused by flap thinning occurred in one patient and healed after pruning and dressing change. The heights of all alveolar ridges were significantly restored, and no serious donorsite complication was observed during the three to six months' follow-up. CONCLUSION: DCIAPF is a reconstructive option for mandibular defects because of its adequate bone tissue and rich blood supply. Satisfactory alveolar ridge restoration greatly facilitates future denture retention. DCIAPF also has a great degree of mobility between the skin paddle and the bone component when appliedin composite oromandibular defect reconstruction. PMID- 26281258 TI - [Application of 1,212 anterolateral thigh myocutaneous flaps in the repair of oral and maxillofacial defects]. AB - OBJECTIVE: To examine the benefits of anterolateral thigh myocutaneous flaps in reconstruction of oral and maxillofacial defects. METHODS: Patients were recruited from February 2002 to June 2013 in the Department of Oral and Maxillofacial Surgery of Central South University. All patients (1,185 patients, 1,212 transferred flaps) underwent reconstructive surgery employing anterolateral thigh myocutaneous flaps. Basic information for all patients including defect side, flap size and type, recipient vessel processing method, donor complications, and postoperative quality of life were recorded and statistically analyzed. RESULTS: Among the 1 212 transferred flaps, 1 176 survived and 36 showed necrosis, for a survival rate of about 97.0%. No cases presented with local serious complications, and 90% of patients achieved good functional recovery and aesthetically acceptable results after reconstruction of oral and maxillofacial defects at various locations using anterolateral thigh myocutaneous flaps. The time for anastomosis of one vein was significantly less than that for two veins (P=-0.000 3), which indicated one vein anastomosis could significantly reduce the operating time. The incidence of venous crisis, the survival rate after treatment, and the rate of venous crisis resulting in flap necrosis were comparable between the groups (P>0.05). CONCLUSION: Anterolateral thigh myocutaneous flaps can be easily obtained and provide a good amount of muscle for filling dead space and fascia lata. These flaps can meet the various requirements of oral and maxillofacial defects. Therefore, the anterolateral thigh myocutaneous free flaps are more suitable for oral and maxillofacial defects than other flaps. PMID- 26281259 TI - [Evaluation of the stress distribution in tooth implant-supported fixed partial prostheses on different bone types under dynamic loads]. AB - OBJECTIVE: This study aims to evaluate the influence of different bone types on the stress distribution in tooth implant-supported fixed partial prostheses by using finite element (FE) analysis. METHODS: Four FE models of mandibular arch containing one implant splinted to the mandibular second premolar were built according to bone types I, II, III, and IV. Dynamic loads of 250 N were applied to the buccal and lingual cusps of the prostheses in different directions to simulate the masticatory cycle. The maximum Von Mises stresses were calculated using the FE analysis software. RESULTS: The maximum Von Mises stresses of the cortical bones were 89.229, 91.860, 125.840, and 158.420 MPa, increasing from type I to type IV, respectively. The maximum Von Mises stresses of the trabecular bone were 58.584, 43.645, 21.688, and 18.249 MPa, decreasing from type I to type IV, respectively. During the process of dynamic loading, the maximum Von Mises stresses of the cortical and trabecular bones followed the order buccal to tongue loading>tongue to buccal loading>vertical loading. CONCLUSION: The results showed that bone type significantly influenced the stress distribution in bones, and that for tooth implant-supported fixed partial prostheses, bone types I and II were a better choice than bone types III and IV. More caution should be exercised when restoring missing teeth using tooth implant-supported fixed partial prostheses in softer bone regions. PMID- 26281260 TI - [Three-dimensional finite element analysis of maxillary anterior teeth retraction force system in light wire technique]. AB - OBJECTIVE: This study aims to construct a three-dimensional finite element model of a maxillary anterior teeth retraction force system in light wire technique and to investigate the difference of hydrostatic pressure and initial displacement of upper anterior teeth under different torque values of tip back bend. METHODS: A geometric three-dimensional model of the maxillary bone, including all the upper teeth, was achieved via CT scan. To construct the force model system, lingual brackets and wire were constructed by using the Solidworks. Brackets software, and wire were assembled to the teeth. ANASYS was used to calculate the hydrostatic pressure and the initial displacement of maxillary anterior teeth under different tip-back bend moments of 15, 30, 45, 60, and 75 Nmm when the class II elastic force was 0.556 N. RESULTS: Hydrostatic pressure was concentrated in the root apices and cervical margin of upper anterior teeth. Distal tipping and relative intrusive displacement were observed. The hydrostatic pressure and initial displacement of upper canine were greater than in the central and lateral incisors. This hydrostatic pressure and initial intrusive displacement increased with an increase in tip-back bend moment. CONCLUSION: Lingual retraction force system of maxillary anterior teeth in light wire technique can be applied safely and controllably. The type and quantity of teeth movement can be controlled by the alteration of tip-back bend moment. PMID- 26281261 TI - [Reliability of iWitness photogrammetry in maxillofacial application]. AB - OBJECTIVE: This study aims to test the accuracy and precision of iWitness photogrammetry for measuring the facial tissues of mannequin head. METHODS: Under ideal circumstances, the 3D landmark coordinates were repeatedly obtained from a mannequin head using iWitness photogrammetric system with different parameters, to examine the precision of this system. The differences between the 3D data and their true distance values of mannequin head were computed. RESULTS: Operator error of 3D system in non-zoom and zoom status were 0.20 mm and 0.09 mm, and the difference was significant (P 0.05). Image captured error of 3D system was 0.283 mm, and there was no significant difference compared with the same group of images (P>0.05). Error of 3D systen with recalibration was 0.251 mm, and the difference was not statistically significant compared with image captured error (P>0.05). Good congruence was observed between means derived from the 3D photos and direct anthropometry, with difference ranging from -0.4 mm to +0.4 mm. CONCLUSION: This study provides further evidence of the high reliability of iWitness photogrammetry for several craniofacial measurements, including landmarks and inter-landmark distances. The evaluated system can be recommended for the evaluation and documentation of the facial surface. PMID- 26281262 TI - [Study on the antibacterial activity of four kinds of nano-hydroxyapatite composites against Enterococcus faecalis]. AB - OBJECTIVE: This study aims to compare and determine a kind of nano-hydroxyapatite composite material with good antibacterial efficacy on Enterococcusfaecalis (E. faecalis) in vitro. METHODS: We investigated the antimicrobial activity of four kinds of nano-hydroxyapatite composites, namely, silver/hydroxyapatite composite nanoparticles (Ag/nHA), yttrium/hydroxyapatite composite nanoparticles (Yi/nHA), cerium/hydroxyapatite composite nanoparticles (Ce/nHA), and hydroxyapatite nanoparticles (nHA), against E. faecalis in vitro using the agar diffusion and broth dilution method by measuring the growth inhibition zone and the minimum inhibitory concentration (MIC), respectively. RESULTS: The agar diffusion test results showed that Ag/nHA displayed an obvious growth inhibition zone, whereas Yi/nHA, Ce/nHA, and nHA showed no influence on E. faecalis. The MIC value of Ag/nHA was 1.0 g.L-1, and the three other materials had no effect on E.faecalis even at the high concentration of 32.0 g.L-1. CONCLUSION: Ag/nHA display a potential antimicrobial efficacy to planktonic E.faecalis. Whereas, the three other kinds of nano-hydroxyapatite composites (Yi/nHA, Ce/nHA, nHA) show no influence. PMID- 26281263 TI - [Effect of different dentin cleaning agents on the bond strength of self-adhesive resin cement to dentin]. AB - OBJECTIVE: This study aims to evaluate the bond strength of a self-adhesive resin cement to dentin by ethylene diamine tetraacetic acid (EDTA) and NaClO. METHODS: Twenty-seven freshly extracted non-carious human premolars were prepared to expose the buccal dentin and randomly divided into three groups: control group (A group), EDTA group (B group) and NaClO group (C group). All teeth were bonded to dentin using a self-adhesive resin cement after the teeth in the A group were processed with distilled water. The B and C group were processed with 3%EDTA and 1%NaClO, respectively. After 24 hours at 37 degrees C water, the shear bond strengths of the twenty-four specimens were measured. All statistical analysis was performed using SPSS 17.0 software package. Each fractured specimen was examined under dental microscope. Three new specimens were cut, and the morphologies of the cement-dentin interface were observed under scanning electron microscope (SEM). RESULTS: The shear bond strength in the A group, B group and C group was (8.55+/-0.63), (8.47+/-0.56) and (12.97+/- 0.59) MPa, respectively. The difference between A group and B group was no statistically significant (P>0.05), whereas the difference between C group and B group (or A group) was statistically significant (P<0.05). SEM observation of the cement-dentin interface in the C group showed good adaptation, but resin tags were not observed. The other two groups showed poor bonding interface. Most of the fractured adhesive dentin surfaces exhibited cohesive failure in the A group and B group. All the fractured adhesive dentin surfaces exhibited cohesive failure in the C group. CONCLUSION: 1% NaClO can increase the bond strength of self-adhesive resin cement to dentin, but 3%EDTA has no effect. PMID- 26281264 TI - [Analysis of different endodontic sealers and strategies of root canal irrigation on the bond strength of fiber posts]. AB - OBJECTIVE: To evaluate the influence of eugenol-containing and resin-containing endodontic sealers on the bond strength of fiber posts using different strategies of root canal irrigation. METHODS: Forty-eight mandibular premolars were endodontically treated. The specimens were randomly assigned into two groups according to different endodontic sealers. Group A used Endofil (eugenol containing endodontic sealer), and group B used AH-plus (resin-containing endodontic sealer). After post space preparation, each group was randomly assigned into three subgroups according to the strategies of root canal irrigation (eight premolars in each subgroup). Group Al and B1: 0.9%NaCl irrigation; Group A2 and B2: 17% ethylene diamine tetraacetic acid (EDTA)+5.25%NaClO+0.9%NaCl irrigation; Group A3 and B3: ultrasonic agitation associated with 1 7%EDTA+5.25%NaClO+0.9%NaCl. One week after the cementation of fiber posts using RelyXTM Unicem, a push-out test was performed to measure the bond strength of the posts. The microstructure of the root canal surface was examined under scanning electron microscope (SEM). RESULTS: The bond strengths of the six groups were as follows: Al (7.96+/-2.23) MPa, A2 (9.95+/-2.89) MPa, A3 (18.88+/-3.69) MPa, B1 (11.41+/-3.71) MPa, B2 (14.00+/-4.04) MPa, and B3 (19.14+/ 3.27) MPa. Statistical analysis revealed a significant interaction between the different endodontic sealers and the strategies of root canal irrigation (P<0.05). Lower bond strength was found in group Al but not in group BI (P<0.05), and the same result was revealed when comparing group A2 and B2. No significant difference was observed between group A3 and B3 (P>0.05). SEM showed that the root canal in group A3 and B3 achieved the cleanest surface with nearly all dentine tubules opened. CONCLUSION: The eugenol-containing endodontic sealer can impair the bond strength of fiber posts compared with the resin-containing sealer when the root canal is irrigated by 0.9% NaCl or 17%EDTA+5.25%NaClO+0.9%NaC. No difference was observed between the two sealers when using 17%EDTA+5.25% NaCIO+0.9%NaCl combined with ultrasonic irrigation. PMID- 26281265 TI - [Precision stomatology: current status and challenges]. AB - The completion of human genome project and the progress in medical practice have inevitably lead to the development of precision medicine, which is a medical model that proposes the customization of medical care including medical decisions, practices, and/or medical products with patient's genetic background, environmental factors and life behavior being taken into account. The current work proposed precision stomatology for the first time, and by integrating data reported in recent literature, we described the current practice of precision stomatology in multiple disciplines in modem dentistry. The clinical significance of precision stomatology and its future challenges have also been discussed. PMID- 26281266 TI - [Application of surgical navigation technology in the treatment of zygomatic fracture]. AB - Zygomatic fracture is one of the most common mid-facial fractures. Zygomatic fracture often leads to open-mouth and chewing dysfunctions, which are often associated with pronounced zygomatic facial deformity, causing psychological and physiological problems in patients. The complicated anatomical structures associated with zygomatic fracture often make treatment difficult. Surgical navigation technology provides a new auxiliary method for improving the treatment results for zygomatic fracture. This review aims to provide a comprehensive overview of the application of surgical navigation technology in the treatment of zygomatic fracture. PMID- 26281267 TI - [Perforated maxillofacial defect repaired by anteromedial thigh flap instead of anterolateral thigh flap: a case report]. AB - Anterolateral thigh flap is perfect for reconstructing maxillofacial soft tissue defects. This tissue has been widely used by clinicians, but often causes operation difficulties because of vascular variation. In this paper, we report a case where anteromedial thigh was used as new donor site when the vascular anatomic variation of anterolateral thigh perforator flap induced a failure in the flap harvest. Moreover, this paper discusses the anatomy and application of anteromedial thigh flap. PMID- 26281268 TI - [Maxillary first molar with twin-root canal in palatal side: two case reports]. AB - Maxillary first molar with twin-root canal in palatal side is rare. This article described two cases of maxillary first molar with twin-root canal. A properly designed and prepared access of the cavity is helpful for the diagnosis and negotiation of the root canal morphology. PMID- 26281269 TI - Medical-Legal Partnerships: Making A Difference in Children's Health Care. PMID- 26281270 TI - Handle with Care: Top Ten Tips a Nurse Should Know Before Caring For a Hospitalized Child with Autism Spectrum Disorder. AB - The diagnosis of autism spectrum disorder is on the rise in the United States. More children with this disorder are requiring hospitalization and have an extended length of stay once hospitalized. The pediatric nurse is often unaware of or unprepared to offer the care that this special population requires. Sharing information obtained through repeated encounters with this population may lead to a less stressful and safer hospital stay for the child with autism, the family, and the pediatric nurse. Items about which the nurse should be aware when caring for a child with autism include the symptoms of autism spectrum disorder, the importance of family involvement, identifying the best way to communicate with the child, minimizing change, incorporating the child's home routine into the stay, creating a safe environment, identifying emotional disturbances, involving a multi-disciplinary team of experts on admission, listening to the family, and creating a record of this information to be shared among staff members. PMID- 26281271 TI - What Is It Like to Be a Child with Type 1 Diabetes Mellitus? AB - Diabetes mellitus is a complex disease that requires significant changes in lifestyle upon diagnosis, which may be difficult for children because of differences in growth and developmental levels. The purpose of this study was to increase our understanding of "what it is like" to be a child with type 1 diabetes mellitus and explore factors that interfere with disease management. Qualitative interviews using puppets constructed by children 7 to 12 years of age were conducted during clinic visits. The interviewer engaged in conversations to examine thoughts, feelings, and daily experiences with the management of diabetes. Results indicated that the children (N = 19) expressed emotions and psychosocial factors that may interfere with their ability to manage diabetes. These included conflicting desires, insecurity, fear, pain, inadequate knowledge, worry about long-term effects, prejudice, rejection, and shame. Findings suggest that during patient teaching at the time of diagnoses and follow-up clinic visits, clinicians address not only the physical aspects of the disease (blood sugar monitoring, insulin administration, diet and exercise management) but also examine emotional and psychosocial needs, and discuss strategies that will promote positive coping as children live with the complexities of growing up with diabetes. PMID- 26281272 TI - Child Witness to Domestic Abuse: Baseline Data Analysis for a Seven-Year Prospective Study. AB - Children who witness the abuse of their mother by an intimate partner suffer negative effects on behavioral functioning. In this study, 300 abused women seeking services for abuse were interviewed regarding how often their child had witnessed the abuse. Baseline data for this study found that boys who witnessed abuse had externalizing and internalizing behavioral problems comparable to boys in clinical treatment. Girls did not display clinically significant behaviors. For evidence-based programs to interrupt the effect of witness to violence on children, empirical data that are gender-specific are needed. Findings support the need to screen mothers for abuse during well-child visits and offer education to all mothers on the possible effects of child witness to violence in the home. PMID- 26281273 TI - Prospective Studies: Looking for Correlations. PMID- 26281274 TI - Parental Vigilance in Caring for Their Children with Hypoplastic Left Heart Syndrome. AB - Hypoplastic left heart syndrome (HLHS) is a complex heart malformation that requires life-saving treatments. Parents experience numerous challenges as they learn to parent a child with complex care requirements. The following research question guided this qualitative study: Is the parenting process among parents of a child with HLHS characterized by exaggerated vigilant parental action, and if so, how does this influence parental response? Situated within a larger program of pediatric cardiology research, this study included data from two grounded theory studies with parents of children with HLHS. This secondary analysis involved a thematic content analysis using sensitizing concepts of uncertainty, protectiveness, support, and mastery of complex care. Transcribed data from 55 interviews with 24 mothers and 17 fathers of young children with HLHS were analyzed for relevant and recurring themes. In mastering skills required to care for their child with HLHS, parents contrasted what was in their hands with what was out of their hands. Vigilant parental actions were evident as parents became skilled at providing complex care. Parents said they were sometimes excessive in their vigilant actions. In retrospect they viewed this vigilance as appropriate in some situations but exaggerated in other situations. Understanding parents' vigilant actions in response to their child's complex care can guide health care providers' interactions with families. Long-term follow up, both clinically and through research, is needed to assess the long-term consequences of exaggerated vigilant parental action on the child, parent, and family, and to determine and evaluate appropriate and timely intervention. PMID- 26281275 TI - Climate Change: It's Our Problem. PMID- 26281276 TI - A 16-Year-Old Female with Nipple Discharge. PMID- 26281277 TI - Risk-Adjusted Staffing to Improve Patient Value. AB - The presence of hospital-acquired conditions, infections, or other adverse events are a reflection of inadequate patient safety and can have short and long-term impacts of quality of life for patients as well as financial implications for the hospital. Using unit-level information to develop a tool, the Patient Risk Assessment Profile, nurses on an inpatient surgical unit proactively assessed patient risk to guide staffing decisions and nurse-patient assignment with the goal to improve patient value, reduce adverse events, and avoid unnecessary hospital costs. Findings showed decreased adverse event rates for patient falls, catheter-acquired urinary tract infection, central line-acquired blood stream infection, and pressure ulcer prevalence after the intervention was implemented. In addition, end-of-shift over-time and patient cost per case decreased as well yielding an operational impact in hospital financial performance. PMID- 26281278 TI - Nurse Fatigue and Shift Length: A Pilot Study. AB - Increasing emphasis on patient quality and concerns about the impact of health care worker fatigue has stimulated efforts for leaders to address patient quality and caregiver satisfaction. Shift length has been associated with nurse fatigue and has become a growing concern in the United States with the routine shift length of 12 hours. In this project, shift lengths from 12 hours to 8 hours for a 4-week period to evaluate fatigue levels associated with 12-hour and 8-hour shifts. Lessons learned from this experience: nurses are agreeable to try a proposed change, numerous ideas should be tried to develop additional innovative solutions to the issue of nurse fatigue, and nurses may not want to work 5 days per week. PMID- 26281279 TI - Modifying State Laws for Nurse Practitioners and Physician Assistants Can Reduce Cost Of Medical Services. AB - "Bending the cost curve" for health care services in the United States challenges policymakers. A cost analysis was undertaken based on what would occur if more physician assistants (PAs) and nurse practitioners (NPs) per capita were deployed over a 10-year period. The State of Alabama was used as a case study because it is one of a handful of U.S. states with restrictive legislation impacting the scope of practice of PAs and NPs. Changing PA and NP scope of practice legislation in Alabama to match states in the upper quartile of collaborative legislation such as Washington and Arizona would increase the employment and distribution of PAs and NPs. Even modest changes in legislation will result in a net savings of $729 million over the 10-year period. Underutilization of PAs and NPs by restrictive licensure inhibits the cost benefits of increasing the supply of PAs and NPs and reducing the reliance on a stagnant supply of primary care physicians in meeting the needs of its citizens. PMID- 26281281 TI - Greater than the Sum of the Parts. PMID- 26281280 TI - The Relationship Between Registered Nurses and Nursing Home Quality: An Integrative Review (2008-2014). AB - Nursing home care is expensive; second only to acute hospital care for inpatient Medicare costs. The increased focus on costs of care accrued by Medicare beneficiaries in nursing homes presents a valuable opportunity for registered nurses (RNs) to further demonstrate quantitatively the value they add to the capacity of the nursing home nursing skill mix to provide cost-effective and efficient quality care. Most of the studies included in this review consistently reported that higher RN staffing and higher ratios of RNs in the nursing skill mix are related to better NH quality. Concerns about the costs of employing more highly skilled RNs and directors of nursing that have the potential to positively influence members of the nursing skill mix will continue to influence nursing home industry hiring practices. For both the advancement of nursing as an applied science and the benefit of society at large, nursing researchers are challenged to better demonstrate how the increased presence of a RN on each shift has the potential to enhance the cost effectiveness, efficiency, and quality of nursing homes. PMID- 26281282 TI - The World Health Organization: Is It Still Relevant? AB - The World Health Organization (WHO) is the United Nation's lead agency for directing and coordinating health. As leaders, nurse executives must advocate for a stronger nursing and midwifery health policy agenda at the global level and a seat at the table on WHO's technical advisory bodies and expert committees. There are no more borders as nurse executives; we are global citizens, leading global change. Nurse leaders hold the master key to shape the world's policies for sustainable global development. PMID- 26281283 TI - The Disease of 'Busyness'. AB - Busyness is anything but impressive, especially when coming from a leader. Sadly, busyness keeps nurse leaders from more worthwhile and important things in their lives, such as authentic, vulnerable relationships. Our collective busyness has become an offensive disease. We have the ability to change our lives internally and externally, professionally and personally. We have nothing to lose but stress and the voice of an unnecessary taskmaster who is continually demanding more and is never satisfied. We'll gain a sense of peace, purpose, health, mindful leadership, and a good dose of meaning and self-respect. PMID- 26281284 TI - [10 years Scientific Institute of Private Health Insurance (WIP)]. PMID- 26281286 TI - [Patients' rights--doctors' duties]. AB - On 26 February 2013 the new "Law on Patients' Rights" (hereinafter also the "Law") became effective. This Law strengthens patients' rights vis-a-vis the insurdnce company and also regulates patients' rights regarding their relation to the doctor. This has consequences for the laws on medical liability all doctors must consider. The doctor's performance is and remains a service and such service does not hold any guarantee of success. Nevertheless, this Law primarily reads as a "law on the duties of physicians". To duly take into account these duties and to avoid mistakes and misinterpretation of the Law, the Ethics Committee of the Consortium of Osteosynthesis Trauma Germany (AOTRAUMA-D) has drafted comments on the Law. Brief summaries of its effects are to be found at the end of the respective comment under the heading "Consequences for Practice". The text of the law was influenced particularly by case law, as continuously developed by the German Federal Court of Justice ("BGH"). The implementation of the Law on Patients' Rights was effected by the newly inserted sections 630a to 630h of the German Civil Code (the "BGB"), which are analysed below. The following comments are addressed to physicians only and do not deal with the specific requirements and particularities of the other medical professions such as physiotherapy, midwifery and others so on. Special attention should be paid to the comments on the newly inserted Duty to inform, which has to be fullfilled prior to any diagnostic or therapeutic procedure (sec. 630c para 2 sentence 1 BGB). Under certain conditions the doctor also has to inform the patient about the circumstances that lead to the presumed occurance of a therapeutic or diagnostic malpractice (sec. 630c para. 2 sentence 2 BGB), based on the manifestation of an undesired event or an undesired outcome. As before, the patient's valid consent to any procedure (sec. 630d BGB) is directly linked to the comprehensive and timely provision of information (sec. 630e BGB). Comprehensive documentation obligations regarding all procedures are stipulated in sec. 630f BGB. As before, the burden of proof still rests with the patient, unless a severe malpractice has been established (sec. 630h BGB). The definition of "severe malpractice" remains unchanged and is based on the case law of the Federal Court of Justice (BGH). The patient's obligations to preserve his or her health and to actively support the process of recovery and securing a positive outcome of the treatment are not explicitly mentioned in the Law. Nevertheless, the patient and the physician need to work closely together to achieve a successful result of the treatment. In case the patient does not give his or her cooperation, the physician should consider terminating the treatment relationship. PMID- 26281285 TI - [Financial incentives on weight loss after rehabilitation]. AB - INTRODUCTION: Increasing rates of obesity and associated diseases and their consequences make the implementation of preventive and counteracting measures necessary. The aim of this study was the examination of the long-term effects of financial incentives on weight loss in obese patients and the identification of influencing factors. METHODS: 700 obese patients were randomly assigned to one of three study conditions: For reaching a pre-defined target weight within 4 months they were rewarded with Euro 150, Euro 300 or not at all. The effect of the incentives on weight loss in different subgroups was compared. After 18 months, other possible influences on weight loss were analyzed by comparing responders and non-responders. RESULTS: Financial rewards led to significant weight loss in all subgroups, whereupon the height of the incentive only mattered in some. After 22 months, for several subgroups, the incentive's effect was still visible. Furthermore, responders showed more healthy behaviour, were better informed and reported more social support. CONCLUSION: Especially for patient groups who do not lose weight in orthodox treatments alone, financial incentives can be an effective supplement. In addition it became clear that this kind of reward programme can be implemented area-wide. PMID- 26281287 TI - [How do physicians code the motoric variable of the Glasgow-Coma-Score?]. AB - A mere 14% gave the right answer according the guidelines: Code the "best motoric answer" of the "upper limb". 86% coded the Glasgow-Coma-Score for the motoric variable falsely and inconsistently. Additionally, the rate of correct answers were higher in physicians in training (37.5%) than in qualified and certified emergency doctors (5%). Emergency doctors post training stated in 68% instances that the variable should be coded according to the neurological results at the upper or lower extremity. Furthermore, they stated that the worst neurological result should be coded (43%). From our data, it appears that the coding of the motoric variable is not done according to the guidelines or is done inconsistently. There are compelling reasons for coding the worst result. However, this procedure is contrary to the guidelines presented by literature. These guideline have never been withdrawn. Emergency doctors obviously code the motoric variable of the Glasgow-Coma-Score with knowledge about the pathophysiology of traumatic brain injuries. The Glasgow-Coma-Score is used for coding the level of consciousness at the site of accident, on admission, for prognosis, in clinical studies and in forensic controversies. Its sensitivity for depth of coma depends on the quality of coding the motoric answer. We interviewed 165 emergency doctors (in training and post training) about the guidelines for coding the motoric variable of the Glasgow-Coma-Score. PMID- 26281288 TI - [The relevance of multiple sclerosis drugs in private health insurance (PHI)]. AB - The development of expenses and prescriptions in the pharmacotherapy for multiple sclerosis (MS) is examined on the basis of prescription data of 14 PHI firms. The drugs for the treatment of MS are among the most top-selling drugs in the PHI. From 2007 to 2012, the expenses increase 2.33-fold. The main cause is the increas of the prescription figures. In 2012, about 8,400 privately insured persons receive an MS drug. The prevalence of MS is 2.3 times higher in women than in men Impro ved diagnostic possibilities and expensive new drugs will lead to a dynamic cost de velopment in the next years. PMID- 26281289 TI - [Chronic elevation of IGF-1 concentrations in a 54-year-old female with acromegalic appearance and somatoform disorder as a challenge to medical opinion]. AB - A 54-year-old woman was referred to the psychiatric clinic with complex somatic whole-body complaints. In absence of organic findings, the diagnosis of somatoform disorder (somatization disorder ICD 10 F45.0) was made. Additionally, due to the typical appearance and chronically elevated IGF-1 (somatomedin C) concentrations, the critical diagnosis of acromegaly was postulated, although no hypophyseal adenoma was detected. The patient was variously assessed and 16 medical and rehabilitation opinions were given with regard to invalidity, particularly by orthopaedic and neurologic specialists. The results varied, even diametrically opposed. However, somatoform disorders or acromegalic appearance and possible medical consequences were not considered sufficiently. The case report encourages experts to deal with complex psychosomatic complaints objectively and unemotionally in medical opinions. PMID- 26281290 TI - [Guideline and medical standard]. PMID- 26281291 TI - [Will work disability due to PTSD soon no longer be an option?]. PMID- 26281292 TI - [How much physical therapy in chronic pain of the musculoskeletal system is medically necessary?]. PMID- 26281293 TI - [Treatment of back pains with biophysical quantum medicine. Is the biofield test a medically necessary diagnostic technique?]. PMID- 26281294 TI - [Insurance medicine evaluation of traumatic rotator cuff rupture]. PMID- 26281295 TI - [ Comment on G.-M Ostendorf: Current treatment concepts in traditional Chinese medicine. Versicherungsmedizin 66 (2014) Heft 4, S. 208]. PMID- 26281296 TI - [Comment on R. Hakimi]. PMID- 26281298 TI - [Exploration of novel therapeutic targets for neuropathic pain based on the regulation of immune cells]. AB - The pathogenesis of neuropathic pain is quite complicated and diverse. Because pre-existing analgesics, such as opioid analgesics and nonsteroidal anti inflammatory drugs, are not sufficient to treat it, it is a serious task to establish a strategy of remedy for neuropathic pain. Recently, increasing evidence suggests that immune cell-mediated neuroinflammation in the nervous system induces central and peripheral sensitization, resulting in chronic pain. Initially, the immune system plays an important role in host defense. Although intravital homeostasis is kept constant by innate and adaptive immunity, the immune system is activated excessively due to infection, stress and tissue injury. Activated immune cells produce and release several kinds of inflammatory mediators, which act directly on sensory neurons and promote a recruitment of immune cells, developing the feedback loop of inflammatory exacerbation. We've focused on the role of crosstalk between immune cells and neurons in peripheral neuroinflammation, and explored a novel candidate for a remedy of neuropathic pain. In this review, we will introduce recent reports and our research work that suggest the functional significance of neuroinflammation in neuropathic pain, and survey possibilities of new strategies for chronic pain from the point of view of basic research. PMID- 26281299 TI - [Association between GSK3beta polymorphisms and the smoking habits in young Japanese]. AB - Schizophrenia and bipolar disorder show high comorbidity with smoking dependence. Several previous studies reported that glycogen synthase kinase 3beta (GSK3beta), which is widely expressed in the brain including the dopamine projection areas such as the amygdala, nucleus accumbens and hippocampus, may play a role in neuropsychiatric disorders and dopamine- and serotonin-mediated behavior. In this study, we have analyzed the association of three single nucleotide polymorphisms (SNPs) within GSK3beta gene (rs3755557, rs334558, rs6438552) with the smoking habits and age at smoking initiation in a sample of 384 young adult Japanese, which included 172 smokers and 212 non-smokers. As a result, rs334558 was significantly associated with smoking habits in genotype frequency and allelic frequency (P < 0.05). Furthermore, higher haplotype 3 (T-T-T) and haplotype 5 (A T-C) frequencies were observed in non-smokers than smokers (P < 0.05). Three functional polymorphisms examined in this study reportedly increase transcriptional activity when they have a high-activation allele such as the A allele of -1727A/T (rs3755557), the T allele of -50T/C (rs334558) or T allele of 157T/C (rs6438552). Thus, it was suggested in this study that changes in GSK3beta activity may have an impact on smoking habits. PMID- 26281300 TI - [Molecular biological properties of the Epstein-Barr virus LMP1 gene: structure, function and polymorphism]. AB - Recent studies indicate that the latent membrane protein 1 (LMP1) encoded by the same name gene of the Epstein-Barr virus (EBV) plays an extremely important role in the pathogenesis of a number of malignant neoplasia. Specifically, LMP1 has the ability to transform human B-lymphocytes in vivo and in vitro and rodent fibroblasts (Rat-1) in vitro. The introduction of the latter into athymic mice leads to tumor development. In addition, expression of the oncoprotein has been often found in EBV-associated tumors at the DNA and constantly at the RNA levels. Having pleiotropic effects, LMP1, participates in the transmission and activation of multiple intracellular signals. It is also involved in the inhibition of key tumor suppressors, has significant influence on proliferation, apoptosis and morphological alteration of the infected cells finally resulting in their transformation. General characteristics of EBV and LMP1 gene as well as functional activity of the encoded LMP1 protein and a brief description of human pathologies associated with the virus have been discussed in this review. The questions concerning the polymorphism LMP1 in EBV-associated pathologies have been also analyzed in details. PMID- 26281301 TI - [The vaccines based on the replicon of the venezuelan equine encephalomyelitis virus against viral hemorrhagic fevers]. AB - The status of the various recombinant DNA and RNA-derived candidate vaccines, as well as the Venezuelan equine encephalomyelitis virus (VEEV) replicon vaccine system against extremely hazardous viral hemorrhagic fevers, were reviewed. The VEEV-based replication-incompetent vectors offer attractive features in terms of safety, high expression levels of the heterologous viral antigen, tropism to dendritic cells, robust immune responses, protection efficacy, low potential for pre-existing anti-vector immunity and possibility of engineering multivalent vaccines were tested. These features of the VEEV replicon system hold much promise for the development of new generation vaccine candidates against viral hemorrhagic fevers. PMID- 26281302 TI - [Comparison of the influenza epidemics in Russia caused by the pandemic virus A(H1N1)pdm09 within the period from 2009 to 2013]. AB - Comparative analysis of the three past epidemics with the participation of the pandemic influenza A(H1N1)pdm09 was conducted according to the results of the epidemiological trials of two WHO National influenza centers for the morbidity, hospitalization, and mortality of the influenza in 59 cities of Russia for the period from 2009 to 2013. The first wave of the pandemic of 2009 was the most severe. Compared with this wave, during the next epidemics of 2011 and 2013, the involvement of urban population in the epidemic was reduced, as well as the morbidity in the people 15-64 years old and schoolchildren 7-14 years old. The duration of the epidemic among the adult population, the mortality rate of the total population, and the mortality rates in all age groups were also decreased. Vice versa, the incidence in the children of preschool age and the elderly people and the duration of the epidemic among children (especially preschool children) were increased. The share of patients 65 years and older, children 0-2 years old, and patients with pathology of the cardiovascular systems among the deceased patients increased to 33.6%. PMID- 26281303 TI - [Comparative study of carbon nanotubes and polymer composites with silver as sorbents of the influenza A and B viruses]. AB - The comparative examination of the interaction of the influenza A and B viruses and fragments of DNA with the carbon nanotubes--composites of polyaniline (PANI) nanotubes and granules containing Ag and without Ag was performed. The increased absorption of the allantois viruses and DNA was demonstrated in composites with Ag. The influence of temperature in the range of 4-36 degrees C was not found to be essential. The intensive absorption took place within the first 15 min of the contact with the sorbents. In total, the properties of the composites of PANI nanotubes + Ag 30% are the most promising for the influenza viruses and DNA absorption in water solutions. PMID- 26281304 TI - [The prevalence of the human rhinoviruses and coronaviruses circulating in the Moscow region during 2007-2012]. AB - The rhinoviruses and coronaviruses are the most common causative agents of the acute upper respiratory tract infection in humans. They include several species that vary in the pathogenicity, some causing severe respiratory tract diseases. In this work, the species prevalence of rhinoviruses and coronaviruses was studied in 92 virus-positive clinical patients that were collected at the area of the Moscow region during the period from 2007 to 2012. Using the real-time PCR the virus circulation has been established for all species common in humans, including three rhinoviruses, HRV A, HRV B, and HRV C, and four coronaviruses, HCoV-NL63, HCoV-229E, HCoV-OC43, and HCoV-HKU1. For eight patients, the identity of the rhinoviruses, including 4 cases of HRV-C, 3 cases of HRV-A, and a single case of HRV-B, was corroborated using partial sequencing of the 5 non-coding regions and phylogenetic analysis. The viruses of HRV-C, HCoV-NL63, and HCoV-OC43 were prevalent in children with severe respiratory diseases. PMID- 26281305 TI - [The ARI etiology among children in Belarus in 2011-2012]. AB - The seasonal distribution of the respiratory viruses for the period of 2011-2012 is presented. The ARI etiological structure among children 0-17 years, who were admitted to the hospital for respiratory disease in Belarus, was defined by the PCR-method. It was found that the etiological agents of the infections were not only influenza viruses A and B, parainfluenza types 1-4, adeno- and respiratory syncytial viruses, but also described boca- and metapneumoviruses. The most complete spectrum of the respiratory viruses was detected among children aged 0-4 years. PMID- 26281306 TI - [A study of the HIV-1 regulatory genes using the polymerase chain reaction]. AB - In this work, a total of 200 samples from the HIV-infected individuals were analyzed: 50 samples from the Saha Republic (Yakutia), 50 samples from the Vologda Region (City of Cherepovets), and 100 samples from the Moscow Region (Moscow and Moscow Region). All samples were obtained from the patients who were not undergoing antiretroviral therapy. It was detected that the regulatory genes vif, vpr, vpu, rev, tat, and nef were amplified with moderate sensitivity after one-stage amplification. When those samples were analyzed by the nested PCR the detection ratio was much higher. While studying nef-gene the phenomena of the splicing in cells cores was detected at the advanced stages of the HIV-infection (3 and 4 stages). At the same time, the splicing was not detected at the earlier stages of the HIV-infection. This effect might be the cause of the transition from asymptomatic stage of the infection to the advanced stage. It was also shown for the first time that the variability of the regulatory genes correlated with the virus subtype. PMID- 26281307 TI - [Detection of potential sites of recombination in the Tick-borne encephalitis virus by the methods of comparative genomics]. AB - The results of the bioinformatic search for the potential sites of the recombination in the genome-wide structures of the tick-borne encephalitis virus (TBEV) through a series of software techniques were presented in this work. The genomes of the 55 TBEV strains were assayed, 21 of them showed the presence of the recombination sites. Recombinant strains belonged to the Far Eastern (19 strains) and European (2 strains) genotypes. 22 sites of the recombination attributed were identified to five types based on position, strain, and regional characteristics. The parental strains were identified based on the genotypic and geographical parameters, which do not contradict the possibility of the formation of the recombinants. Nearly two-thirds of the sites are located in the regions of NS4a and NS4b genes, which are the "hot spots" of the recombination, most of them being concentrated in the gene NS4. It was shown that the recombination processes did not occur at the level of the genotypes (European genotype) or certain groups within the genotype (Far East) and were typical of the peripheral populations. PMID- 26281308 TI - Does Glp-2 have a protective effect on cerebral ischemia/reperfusion model? AB - BACKGROUND/AIM: To investigate the neuroprotective effects of glucagon-like peptide 2 (Glp-2), which increases cerebral blood flow, on the hippocampal complex after cerebral ischemia/reperfusion (I/R) injury in rats. MATERIALS AND METHODS: Animals were randomized into 4 groups: sham, I/R + 0.9% NaCl, I/R + pre Glp-2, and I/R + post-Glp-2. Cerebral ischemia was performed via the occlusion of the bilateral internal carotid artery for 40 min and continued with a reperfusion process. At the end of 6 h of reperfusion, animals were decapitated in all groups and brain tissues were removed. Malondialdehyde (MDA) and natural intracellular antioxidant glutathione (GSH) levels and myeloperoxidase (MPO) activities were measured in the left hippocampal tissue. The right hippocampal tissues of all group members were taken for histopathologic study. RESULTS: MDA levels and MPO activities increased from Group I to Group II and decreased from Group II to Groups III and IV. On the other hand, GSH levels were not significantly different among the groups. The number of apoptotic hippocampal tissue cells increased from Group I to Group II and decreased from Group II to Groups III and IV. CONCLUSION: Our preliminary study revealed that Glp-2 treatment may decrease oxidative damage from I/R in cerebral tissue. PMID- 26281309 TI - Effects of prenatally exposed diclofenac sodium on rat heart tissue: a stereological and histological study. AB - BACKGROUND/AIM: Diclofenac sodium (DS) can cross the placental barrier and affect the fetus, and its consumption during pregnancy may cause developmental malformation of embryos. This study investigates the effect of prenatally applied DS on the quantitative morphology of the adult rat heart. MATERIALS AND METHODS: Pregnant rats were divided into three groups (control, sham, and test). The rats in the test group were injected with DS; the control group received physiological saline (1 mL; 1 mg/kg, i.m.) from the 5th to the 20th day of pregnancy; and the rats in the sham group were not injected at all. At the 20th postnatal week, all the offspring were euthanized under deep anesthesia and tissue samples were obtained by perfusion fixation. After routine histological procedures, the paraffin sections were stained with hematoxylin and eosin and examined stereologically and histologically. RESULTS: The volume of the cardiac ventricle wall of each offspring rat was estimated using Cavalieri's principle. The volume of the ventricle walls of the test group was found to be significantly less than that of the controls. CONCLUSION: Further studies are required to determine how DS has this effect, by reducing the number of myocytes and decreasing the size of these cells affecting the connective tissue. PMID- 26281310 TI - The expression profile of aquaporin 1 in rat myocardium after severe burns. AB - BACKGROUND/AIM: To investigate the myocardial expression profile of aquaporin 1 (AQP1) in rats after severe burns. MATERIALS AND METHODS: Ninety healthy male adult Wistar rats were randomly assigned to the following treatments: sham operation (control group, n = 6), immediate fluid resuscitation treatment post scalding (IF group, n = 42), and delayed fluid resuscitation treatment after scalding (DF group, n = 42). At 3, 6, 12, 24, 48, 72, and 120 h after scalding, myocardial water contents were assayed and AQP1 expressions were detected by real time polymerase chain reaction and western blot. The AQP levels in the myocardium at 12 h after scalding were assayed by gene microarrays. RESULTS: Scald injuries resulted in significantly synchronized increases in the myocardial water contents and the myocardial mRNA and protein expression of AQP1, with a peak at 12 h after scalding. Rats receiving delayed fluid resuscitation treatment had more severe myocardial edema and significantly higher myocardial AQP1 expressions than the rats receiving immediate fluid resuscitation treatment. The mRNAs of 6 other AQPs (AQP2, 3, 4, 6, 7, and 12b) were found to be changed in the myocardium among rats with different treatments. CONCLUSION: AQP1 may play a functional role in the development of myocardial edema after scalding. Targeting AQP1 may provide opportunities for therapeutic intervention in myocardial edema following severe burns. PMID- 26281311 TI - Effects of grape seed extract on oxidative stress and antioxidant defense markers in streptozotocin-induced diabetic rats. AB - BACKGROUND/AIM: To evaluate the effects of grape seed extract (GSE) supplementation on oxidative stress and antioxidant markers in streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: Thirty-six male rats were divided into the following four groups: control, GSE-supplemented control, diabetic, and GSE-supplemented diabetic. Beginning on day 7 after STZ injection, the rats were administered GSE (100 mg kg(-1) day(-1) in drinking water for 6 weeks. At the end of week 6, rats were sacrificed by cardiac puncture. Plasma nitric oxide (NO) levels and xanthine oxidase (XO), adenosine deaminase (ADA), and glutathione peroxidase (GPx) activities were analyzed. RESULTS: Both XO and ADA activities increased and NO levels decreased in diabetic rats (P < 0.05). GSE supplementation normalized all of these changes. Antioxidant enzyme activities decreased in diabetic rats compared to the controls (P < 0.05). GSE supplementation increased antioxidant enzyme activities in both diabetic and healthy rats (P < 0.05). CONCLUSION: These findings suggest that 6 weeks of oral GSE supplementation may prevent oxidative stress and improve antioxidant status in diabetic rats. PMID- 26281312 TI - Toxic potentials of ten herbs commonly used for aphrodisiac effect in Turkey. AB - BACKGROUND/AIM: Sexual dysfunction is a serious problem worldwide. In Turkey, herbal products are used by some people suffering from sexual dysfunction. Despite their therapeutic advantages, some constituents of herbs are potentially toxic and pose health risks because they can be bought from the market without a prescription. Therefore, we aimed to determine the safety of herbs possessing aphrodisiac effects, chosen on the basis of their frequency of medicinal use and commercial importance in Turkey. MATERIALS AND METHODS: Ten herbs (Anethum graveolens, Carthamus tinctorius, Citrus aurantium, Cocos nucifera, Glycyrrhiza glabra, Melissa officinalis, Nigella arvensis, Pinus pinea, Prunus mahaleb, and Zingiber officinale) were extracted with water, methanol, and chloroform. The cyto- and genotoxic potentials of the extracts were assessed using an MTT test on a rat kidney cell line and an Ames assay in Salmonella typhimurium strains, respectively. RESULTS: In the cytotoxic evaluation, IC50 values were 1.51-31.4 mg/mL for the methanol and chloroform extracts, while the water extracts were not cytotoxic. In the genotoxic evaluation, it was revealed that the water extracts had more mutagenic activity than the chloroform and methanol extracts. Water extract of M. officinalis was shown to have the most genotoxic activities to TA100 (+/-S9) and TA98 (-S9). CONCLUSION: These results might be useful in determining the toxic effects of herbs and lead to precautions being taken in regards to their consumption. PMID- 26281313 TI - Prevention of methotrexate-induced nephrotoxicity by concomitant administration of garlic aqueous extract in rat. AB - BACKGROUND/AIM: Methotrexate (MTX) has been widely used for treatment of cancer and rheumatoid arthritis, but its use has been limited by its nephrotoxicity. This study was carried out to determine whether garlic exerts a protective effect against MTX-induced nephrotoxicity. MATERIALS AND METHODS: Nephrotoxicity was induced in rats after a single i.p. injection of MTX (20 mg/kg). Garlic extract (1 mL/100 g b.w.) was given orally for 7 days before and after MTX administration. Serum samples were collected to evaluate urea, creatinine, sodium, phosphorous, potassium, and calcium. Reduced glutathione, catalase, adenosine deaminase, nitric oxide, and malondialdehyde were measured in renal tissue. Tubular injury was evaluated by histopathological examination. RESULTS: MTX increased urea and creatinine levels and led to imbalances in some electrolytes. It also depleted renal antioxidant enzyme levels and increased malondialdehyde, adenosine deaminase, and nitric oxide levels. Histopathological examination showed glomerular and tubular alterations. Pretreatment with garlic significantly improved renal function and increased renal antioxidant enzyme activities. Furthermore, garlic reduced renal oxidative stress and prevented alterations in renal morphology. CONCLUSION: Garlic treatment has a reversible biochemical and histological effect upon MTX-induced nephrotoxicity. PMID- 26281314 TI - The effect of vitamin E and L-carnitine against methotrexate-induced injury in rat testis. AB - BACKGROUND/AIM: Methotrexate (MTX), used commonly as an antimetabolite drug in cancer therapy, leads to acute toxic side effects in tissues or organs containing rapidly dividing cells, such as bone marrow, gastrointestinal mucosa, and seminiferous tubules. In this study, we investigated the protective effects of vitamin E and L-carnitine against MTX-induced injury in rat testis. MATERIALS AND METHODS: Rats were divided into 4 groups, including the control group. The study took 17 days and the animals received daily doses of 0.5 mL/kg saline, 250 mg/kg vitamin E, or 500 mg/kg L-carnitine intraperitoneally. The experimental groups received 20 mg/kg methotrexate intraperitoneally on days 3 and 10. RESULTS: Weight loss, testicular weight loss and marked histological injuries, increased malondialdehyde levels, and decreased superoxide dismutase levels were only observed in the MTX-treated groups. Vitamin E and L-carnitine treatments did not affect MTX-induced weight loss or testicular weight loss, but they inhibited MTX induced testicular histological injuries. Vitamin E and L-carnitine treatments suppressed the increases in malondialdehyde levels and the decreases in superoxide dismutase levels. CONCLUSION: Vitamin E and L-carnitine treatments decreased MTX-induced testicular histological injuries, and these results were supported by biochemical measurements. PMID- 26281315 TI - Chronology of estrogen receptor expression in testes of mouse embryos. AB - BACKGROUND/AIM: To localize and determine the time of expression of estrogen receptors (ERs) in testes of mouse embryos by histology and immunohistochemistry. MATERIALS AND METHODS: Fifty-four mature Swiss-Webster mice (Mus musculus) were used. Group 1 consisted of 34 mature pregnant females, 3 of which were sacrificed every day from 10.5 to 20.5 days postcoitus (dpc). One testis was removed from their embryos and processed for histology and immunohistochemistry. Group 2 consisted of 20 postnatal mice: 5 postpartum (P0) males, 5 males 4 weeks old, 5 males 8 weeks old, and 5 females 4 weeks old. RESULTS: The first nuclear detection of ERs was observed in embryonic male gonads at 11.5 dpc, and a highly significant increase (P < 0.01) was observed at embryonic days 11.5, 13.5, 15.5, 16.5, 17.5, and 19.5, with a peak at 17.5 dpc and continuing to 20.5 dpc. ER expression increased further after birth. CONCLUSION: Expression of ERs occurred at certain days during mouse embryonic development, indicating the need for estrogen for certain metabolic or morphological events occurring at these days. After birth, estrogen played an important role in proliferation and maturation of certain cells in the testes. Another rise in ER expression occurred during puberty in the mature testis. PMID- 26281316 TI - Caffeic acid phenethyl ester protects lung alveolar epithelial cells from cigarette smoke-induced damage. AB - BACKGROUND/AIM: To evaluate the influence of caffeic acid phenethyl ester (CAPE) on cigarette smoke (CS)-induced cell damage, oxidative stress, and inflammation in human alveolar epithelial cells. MATERIALS AND METHODS: A549 alveolar epithelial cells were divided into control, CS exposure, CAPE, and CS+CAPE treatment groups. Undiluted CS-exposed medium (100%) and three dilutions (50%, 25%, and 10%) of CS-exposed media were applied to cultured A549 cells, which were analyzed after 3 h of incubation. Viability was measured by MTT assay, the gene expressions were evaluated by real-time PCR, and spectrophotometric techniques were used for biochemical assessments. RESULTS: While CS exposure markedly reduced cellular viability by 32% after 3 h of incubation, 2.5 uM CAPE treatments prevented CS-induced cell death by 40% in the cells. CS exposure triggered lipid peroxidation and depleted antioxidant capacity through inhibiting catalase activity and depleting glutathione levels. Moreover, CS increased nitric oxide production via upregulation of iNOS expression. CAPE treatment significantly restored antioxidant capacity and prevented lipid peroxidation. Cigarette smoke exposure induced inflammation by significantly upregulating TNF-alpha, IL-1beta, and COX-2 mRNA expressions (3-, 2- and 25-fold, respectively). CAPE treatment of A549 cells significantly reversed the inflammation. CONCLUSION: CAPE may potentially represent a new therapeutic option in the prevention of CS-induced lung damages. PMID- 26281317 TI - Effect of pioglitazone, quercetin, and hydroxy citric acid on vascular endothelial growth factor messenger RNA (VEGF mRNA) expression in experimentally induced nonalcoholic steatohepatitis (NASH). AB - BACKGROUND/AIM: Vascular endothelial growth factor (VEGF) is associated with various ischemic and inflammatory diseases, and plays an important role in the development of liver fibrosis and hepatocarcinogenesis in nonalcoholic steatohepatitis (NASH). In this study, the comparative effect of pioglitazone, quercetin, and hydroxy citric acid on VEGF mRNA in experimentally induced NASH was investigated. MATERIALS AND METHODS: The experimental protocol consisted of five groups: control, NASH, NASH + pioglitazone, NASH + quercetin, and NASH + hydroxy citric acid. The VEGF mRNA expression was evaluated by reverse transcription polymerase chain reaction (RT- PCR) analysis for all experimental groups, and the levels of VEGF mRNA were quantitatively measured by densitometry. RESULTS: A higher expression of VEGF mRNA was found in the hepatic cells of rats with experimentally induced NASH compared to the control group. A very mild increase in VEGF mRNA expression was observed in the rats treated with quercetin. In contrast, a mild increase in the expression of VEGF mRNA was observed in the rats treated with pioglitazone and hydroxy citric acid. CONCLUSION: Quercetin exhibited an effective inhibition of VEGF mRNA expression, while a lower inhibition of the VEGF mRNA level was observed in the hydroxy citric acid- and the pioglitazone-treated rats. PMID- 26281318 TI - Characterization of HCV genotype 4d infections in Kayseri, Turkey. AB - BACKGROUND/AIM: The frequency of genotype 4 hepatitis C virus (HCV) infections is significantly higher in Kayseri compared to other provinces in Turkey. We aimed to characterize genotype 4 infections in Kayseri by analyzing the demographic and laboratory data of218 HCV RNA-positive, treatment-naive patients admitted to the Kayseri Training and Research Hospital in 2010 and 2011. MATERIALS AND METHODS: The distributions of sex, age, and viral loads of these patients with respect to HCV genotypes were analyzed. We also characterized the type 4 sequences at the subtype level. Randomly selected sera from 32 of the 72 genotype 4 patients from this cohort were subjected to PCR amplification in the NS5B region and further characterized by sequencing and phylogenetic and molecular clock analysis. RESULTS: Distribution rates of HCV genotypes 1, 4, and 2 in the 218 patients were 62.4%, 33.0%, and 4.6%, respectively. Most of the patients infected with types 1 and 4 were over the age of 40 and female. The NS5B sequences of 32 Kayseri genotype 4 isolates were closely related with type 4d sequences but formed a separate cluster. CONCLUSION: The introduction of type 4d HCV into the Kayseri region probably took place 30-75 years ago, as predicted by molecular clock analysis. PMID- 26281319 TI - Differences in the effectiveness of serum biomarkers for the diagnosis of bacterial infections in adult and elderly patients admitted to the emergency department. AB - BACKGROUND/AIM: This study aimed to evaluate the superiority of procalcitonin (PCT), C-reactive protein (CRP) levels, white blood cell (WBC) counts, and erythrocyte sedimentation rate (ESR) in discriminating among infection, systemic inflammatory response syndrome (SIRS), and sepsis, and their differences according to age groups. MATERIALS AND METHODS: The patients were divided into an adult group and a geriatric group (over 65 years) and classified according to the presence of infection, SIRS, and sepsis. The patients' laboratory values (PCT, CRP, WBC, ESR), demographic characteristics, and vital signs were taken into consideration. RESULTS: When the laboratory parameters were evaluated, there were no significant differences in the PCT, WBC, and ESR values between the age groups (P > 0.05). CRP was significantly higher in the adult patient group compared to the geriatric group (P < 0.001). When the two groups were compared in terms of infection, there were no significant differences in the PCT levels and the WBC count (P > 0.05) in SIRS and sepsis. In addition, the CRP levels and the ESR were significantly higher in the adult sepsis patients when compared with the geriatric patients (P < 0.001). CONCLUSION: PCT levels do not distinguish among infection, SIRS, and sepsis in adult and geriatric age groups. PMID- 26281320 TI - Prospective investigation of the hypothalamo-pituitary-adrenal axis in patients with tularemia. AB - BACKGROUND/AIM: To investigate prospectively the hypothalamo-pituitary-adrenal (HPA) axis by adrenocorticotropic hormone (ACTH) stimulation test. MATERIALS AND METHODS: Tularemia was diagnosed according to guidelines. An ACTH stimulation test (1 ug) and a dexamethasone suppression test (DST; 1 mg) were performed in patients in the acute phase of tularemia before antibiotic treatment and in the chronic phase. RESULTS: Nineteen patients (mean age: 41.0 +/- 13.2 years; 57.9% female) with tularemia were enrolled in the study in 2011 and 2012. Cortisol response to ACTH stimulation test was sufficient in all patients during the acute phase. After the DST, the cortisol was not suppressed during the acute phase in only one patient. The median control time of 11 patients after acute tularemia was 13 months. During the chronic phase, cortisol response to ACTH stimulation was normal in all patients, and after DST cortisol was suppressed in all patients. The peak cortisol level after the ACTH stimulation test in the acute phase was higher than that in the chronic phase, but the difference was not statistically significant. CONCLUSION: The HPA axis of patients with tularemia was not significantly affected in the acute and chronic phases. PMID- 26281321 TI - Clinical characteristics of 75 pandemic H1N1 influenza patients from Turkey; risk factors for fatality. AB - BACKGROUND/AIM: The 2009 influenza A (H1N1) pandemic caused mild to severe illnesses and led to death in some cases. In this study, we aimed to evaluate the relationship between the serum D-dimer levels, CURB-65 scores, and the severity of pneumonia among patients with H1N1 infections. MATERIALS AND METHODS: Sixty eight patients who had probable H1N1 infections were evaluated by clinical, radiological, and laboratory methods. The H1N1 strain was specified by reverse transcription-polymerase chain reaction. Of 55 patients diagnosed with pneumonia, 18 exhibited H1N1 positivity and 37 patients did not. RESULTS: CURB-65 scores of pneumonia patients with H1N1 (group 1) were higher than those of patients without H1N1 (group 2) (P = 0.02). The D-dimer levels of group 1 were higher than those of group 2 (P = 0.001). Moreover, there was a positive correlation between D dimer levels and CURB-65 scores in patients with H1N1-associated pneumonia (P = 0.001; r = 0.89). CONCLUSION: Increased D-dimer levels were observed in pneumonia patients with H1N1 infection, which predicted the severity of pneumonia. PMID- 26281322 TI - Correlation between antibiotic resistance and virulence of Pseudomonas aeruginosa clinical isolates. AB - BACKGROUND/AIM: Virulent Pseudomonas aeruginosa. is frequently life-threatening and often challenging to treat, and the emergence of multidrug-resistant isolates presents a critical problem for patients. The aim of the study was concerned with molecular analysis of the virulence factors and antimicrobial resistance profile of multidrug-resistant P. aeruginosa (MDRPA). MATERIALS AND METHODS: Out of 44 MDRPA isolates, 12 isolates representing different resistance profiles and sources of samples were selected for further molecular studies. Polymerase chain reaction (PCR) approaches were applied to identify the genes implicated in antimicrobial resistance or virulence factors in the selected MDRPA isolates. RESULTS: Multidrug-resistance (pstS), beta-lactamase (IMP7, IMP10, IMP13, and IMP25), and extended spectrum beta-lactamase (blaOXA50) genes were detected in all of the selected MDRPA isolates. However, only 4 (33%) MDRPA isolates were positive for the presence of the extended spectrum beta-lactamase (blaOXA2) gene. Furthermore, the hemolytic phospholipase C precursor gene (plcH) was detected in all PCR products of the tested MDRPA isolates while the exotoxin A (toxA) gene was absent. Other virulence genes were detected with variable percentage in tested isolates. CONCLUSION: The statistical analysis revealed a significantly positive correlation (r = 0.779, P = 0.002) between virulence factors and antimicrobial resistance marker profiles of the tested MDRPA isolates. PMID- 26281323 TI - Diagnostic and prognostic value of procalcitonin and sTREM-1 levels in sepsis. AB - BACKGROUND/AIM: Sepsis is still a major cause of morbidity and mortality despite the improvements in diagnosis and treatment. The aim of this study was to investigate the values of procalcitonin and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in the differential diagnosis of patients with sepsis and noninfectious systemic inflammatory response syndrome (NI-SIRS) and measure their importance in the prognosis of patients with sepsis. MATERIALS AND METHODS: This prospective study included 41 NI-SIRS and 33 sepsis patients hospitalized in Celal Bayar University Hospital, Manisa, Turkey. Blood samples were taken from NI-SIRS patients on days 0 and 3 and from sepsis patients on days 0, 3, 4, 7, and 14. Clinical status of the patients was determined with the SOFA scoring system. RESULTS: The SOFA scoring system and procalcitonin and sTREM-1 measurements were significant in the differential diagnosis of sepsis and NI-SIRS patients. The SOFA scoring system was considered the most important indicator in determining the prognosis of sepsis patients. Procalcitonin and sTREM-1 levels increased progressively in nonsurvivors and decreased in survivors, but changes were statistically insignificant. CONCLUSION: In the differentiation of sepsis and NI-SIRS, and evaluation of the prognosis of sepsis, combined measurements of procalcitonin and sTREM-1 levels are important. PMID- 26281324 TI - Comparison of the contamination rates of culture media used for isolation and identification of dermatophytes. AB - BACKGROUND/AIM: Mycological media that promote spore production are essential for the diagnosis of dermatophytosis. However, these culture media frequently become contaminated by multiple fungal or bacterial species during culture. The aim of this study was to compare the contamination rates of 6 culture media used for the isolation and identification of dermatophytes, including Borelli's lactritmel agar (BLA), brain-heart infusion agar (BHIA), Lowenstein-Jensen agar (LJA), malt extract agar (MEA), potato dextrose agar (PDA), and Sabouraud glucose agar (SGA). MATERIALS AND METHODS: Agar plates were inoculated with 43 well-characterized dermatophyte strains, belonging to the genera Arthroderma, Epidermophyton, Microsporum, or Trichophyton. The agar plates were incubated at 26 degrees C and examined every 5 days for 1 month. RESULTS: By the end of the incubation period, 97 of the 258 plates (37.6%) were contaminated by fungi. No bacteria were detected. Overall, BLA demonstrated the lowest rate of contamination, followed by SGA, MEA, BHIA, PDA, and LJA. Sequencing of the internal transcribed spacer region rDNA of the contaminant fungi revealed that Aspergillus and Penicillium species were the most common contaminants. CONCLUSION: These results suggest that nonenriched culture media types, such as BLA or SGA, reduced contamination during dermatophyte subculture. PMID- 26281325 TI - Elevated serum matrix metalloproteinase-2 and -9 and their correlations with severity of disease in patients with community-acquired pneumonia. AB - BACKGROUND/AIM: To determine the role of matrix metalloproteinases (MMPs) and their relationship with the clinical course of community-acquired pneumonia (CAP). MATERIALS AND METHODS: Sixty-two consecutively hospitalized patients with CAP were enrolled and their pneumonia severity index (PSI), time to clinical stability (TCS), treatment response, and complications were recorded. The pre- and posttreatment serum concentrations of MMPs and their inhibitors were analyzed by ELISA. The activities of MMPs were evaluated by gelatin zymography. RESULTS: MMP-2 and -9 serum levels and their activities were higher in CAP patients than controls (P < 0.001 and P < 0.001, respectively). Low-risk patients had lower levels of MMP-2 and TIMP-1 than high-risk patients (P = 0.044, P = 0.001, respectively). Pretreatment serum TIMP-1 level was higher in patients with TCS of >3 days (P = 0.004) and was correlated with oxygenation and PSI scores. Posttreatment serum levels of MMP-9 and TIMP-1 were decreased after antibiotics (P = 0.000 1 and P = 0.0 17, respectively). CONCLUSION: Although MMP-2, MMP-9, and TIMP-1 correlate with many poor prognostic factors, more studies are required to prove their possible role in predicting the severity of CAP. PMID- 26281326 TI - Comparison of helmet and facial mask during noninvasive ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease: a randomized controlled study. AB - BACKGROUND/AIM: Noninvasive mechanical ventilation (NIMV) is an approach to prevent complications in acute respiratory failure. In this study we aimed to compare the efficacy of a full face mask and a helmet in chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Fifty patients were divided randomly into 2 groups as full face mask (Group F) and helmet (Group H). Demographic data, forced expiratory volume at 1 s (FEV1), additional disease, hemodynamic parameters, respiratory rate, APACHE II score, peripheral O2 saturation (SpO2), arterial blood gases (ABG), patient tolerance scale (PTS) score, and fraction of inspired oxygen (FiG2) were recorded. Parameters were recorded as follows: 20 min before the NIMV; every 30 min of NIMV until 120 min; 30 min, 24 h, and 48 h after NIMV; and prior to intensive care unit discharge. RESULTS: The SpO2, PTS, ABG, complication rate, and APACHE II scores were not different between the groups (P > 0.05). The decrease in PaCO2 was statistically significant at 60 min in Group F (P < 0.05), and there was no statistical difference in Group H (P < 0.05) according to initial PaCO2 values. CONCLUSION: Both masks are efficient in improving the patients' outcome in COPD, but the decrease in PaCO2in the helmet group was slower than in the full face mask group. PMID- 26281327 TI - The expression and clinical effects of alpha-methylacyl-CoA racemase (AMACR/ P504S) as an immunohistochemical marker in malign pleural mesothelioma. AB - BACKGROUND/AIM: Alpha-methylacyl-CoA racemase (AMACR), an intracellular enzyme involved in lipid metabolism, has emerged as an immunohistochemical marker for many types of cancer. Recent studies about the role of lipid metabolism in pathogenesis of mesothelioma have brought up some positive results. This study was conducted to investigate AMACR expression in the diagnosis of malignant pleural mesothelioma (MPM) and the correlation of this marker with clinical characteristics and survival. MATERIALS AND METHODS: The clinicopathologic characteristics and resection materials of 71 patients were reviewed retrospectively. AMACR expression was evaluated immunohistochemically. The correlations among AMACR expression, clinicopathologic factors, and survival were investigated. RESULTS: AMACR expression was detected in 42.3% of the study group. The specificity and sensitivity of AMACR immunostaining in detecting mesothelioma were 41.1% and 42.3%, respectively. AMACR-positive and negative groups were similar for age, sex, smoking history, tumor diameter, lymph node involvement, differentiation, T-N factor, and stage. Overall survival was not significantly different between the groups, either. CONCLUSION: The sensitivity of immunostaining was not high enough to use AMACR as a diagnostic tool in MPM. AMACR expression did not have a prognostic value in MPM, either. PMID- 26281328 TI - Short-term effect of transcatheter aortic valve implantation on QT dispersion. AB - BACKGROUND/AIM: Electrophysiological changes are observed following mechanical stretches due to pressure overload in patients with severe aortic stenosis (AS). The electrical instability occurs after depolarization and dispersion of repolarization. The aim of this study was to evaluate changes in ventricular repolarization following transcatheter aortic valve implantation (TAVI). MATERIALS AND METHODS: Thestudypopulationincluded 100 consecutive patients with severe AS thatunderwent TAVI. Electrocardiography (ECG) was performed at baseline, immediately after TAVI, and 1 week after TAVI. RESULTS: The mean age of the patients was 78.2 +/- 7.2 years. Thirty-four (34%) of the patients were male and 66 (66%) were female. Compared to the baseline, mean QT dispersion (QTd) immediately after TAVI and 1 week after TAVI decreased significantly (82.8 +/- 26.5,75.6 +/- 25.2, and 65.8 +/- 28.3, respectively, P < 0.001). Likewise, compared to the baseline, mean corrected QTd (QTcd) immediately after TAVI and 1 week after TAVI decreased significantly (84.7 +/- 25.2, 76.7 +/- 30.8, and 69.1 +/- 31.4, respectively, P < 0.001). CONCLUSION: QTd is indicative of heterogeneity of ventricular refractoriness and is prolonged in patients with AS. Following TAVI, a decrease in QTd might reduce the risk of ventricular arrhythmia in patients with severe AS. PMID- 26281330 TI - Correlation between serum levels of vitamin B12 and anti-Helicobacter pylori IgA antibodies in vitamin B12 deficient Palestinian patients. AB - BACKGROUND/AIM: H. pylori infection and vitamin B12 (vB12) deficiency have high prevalence rates among Palestinians. It was observed that most people who suffered from vB12 deficiency were positive for H. pylori. MATERIALS AND METHODS: The correlation between H. pylori infection and vB12 deficiency was investigated in a representative segment of the Palestinian population. ELISA was used to determine levels of vitamin B12 (vB12) and anti-H. pylori IgA in sera from 238 participants from Al-Khalil district (Hebron), Palestine. RESULTS: There was a strong negative Pearson's correlation coefficient (r = -0.45; P = 0.00001) between levels of anti-H. pylori IgA and vB12 levels in sera drawn from 238 participants (133 patients and 105 control subjects). Two important contaminating variables were identified in this study: healthy control subjects with elevated anti-H. pylori IgA titers and vB12-deficient patients testing negative for anti H. pylori IgA antibodies. The exclusion of the sources of contamination resulted in a stronger negative correlation; r = -0.58 (P = 0.00001). CONCLUSION: The study provided a good screening system that may predict vB12 deficiency before its actual manifestation. If not treated, asymptomatic subjects showing increased anti-H.pylori IgA titers (> 15 NTU/mL) are likely to be at risk of developing vB12 deficiency. PMID- 26281329 TI - Serum Lp-PLA2: as a novel viewpoint in periodontal treatment of hyperlipidaemics. AB - BACKGROUND/AIM: To evaluate the effects of periodontal treatment on serum lipoprotein-associated phospholipase A2 (Lp-PLA2) and C-reactive protein (CRP) levels in hyperlipidaemic patients with periodontitis. MATERIALS AND METHODS: The study included 52 hyperlipidaemics and 28 systemically healthy controls (C) with periodontitis. Of the 52 hyperlipidaemics, 29 received a suggested diet (HD), and 23 of them were prescribed statin (HS). Clinical periodontal parameters, serum lipids, Lp-PLA2, and CRP levels were assessed at the baseline and 2 months after the completion of the nonsurgical periodontal treatment (2MPT). Serum parameters were also evaluated 1 week following the periodontal treatment (1WPT). RESULTS: At the baseline, patients in the HS group had a higher percentage of bleeding on probing than those in the C and HD groups. Hyperlipidaemics had higher serum triglyceride levels than the control group at 2MPT compared to the baseline. At 2MPT, the levels of Lp-PLA2 in the HS group were significantly higher compared to the baseline and 1WPT. There were no statistically significant differences in CRP levels between study periods for all groups. CONCLUSION: The periodontal treatment may affect the inflammatory control of hyperlipidaemic patients with periodontitis via increased Lp-PLA2 levels and severity of the impaired lipid metabolism. These findings may be important regarding the therapeutic strategies for hyperlipidaemics with periodontitis. PMID- 26281331 TI - Relationship among MIF, MCP-1, viral loads, and HBs Ag levels in chronic hepatitis B patients. AB - BACKGROUND/AIM: To determine whether macrophage migration inhibitory factor (MIF) and monocyte chemoattractant protein-1 (MCP-1) levels in patients with hepatitis B (HB) are different than in normal individuals and whether the HB surface antigen (HBs Ag) level and viral load are correlated with each other and with the two aforementioned parameters. MATERIALS AND METHODS: Sera were obtained from 52 chronic active HB (CAHB) patients and 33 healthy controls, and their MIF and MCP 1 levels were measured. Statistical analyses were performed. A value of P < 0.05 was considered statistically significant. RESULTS: The MIF and MCP-1 values of the control group were increased compared to those of the CAHB group. The MIF and MCP-1 levels were negatively correlated with HBs Ag levels and viral loads. The MIF and MCP-1 levels were positively correlated. The HBs Ag levels and the log10 of the viral loads were positively correlated. CONCLUSION: We conclude that the negative correlation of MIF and MCP-1 with viral load and HBs Ag levels may be due to T-cell deficiency, antinuclear antibody seropositivity, and/or inhibition of chemokine ligand 2 receptors by viral antigens. More studies with a greater number of subjects are needed to evaluate the potential role of MIF and MCP in CAHB. PMID- 26281332 TI - In vitro efficacy of frozen erythrocytes: implementation of new strategic blood stores to alleviate resource shortage (issue revisited). AB - BACKGROUND/AIM: Currently, the provision of blood products largely depends on walking blood banks and limited amounts of stored blood with short shelf lives. We aimed to compare the efficacy of erythrocyte concentrate (ECs) by pre- and postfreezing in vitro tests. MATERIALS AND METHODS: In our study, 10 ECs were glycerolized, frozen, thawed, and then deglycerolized using the Naval Blood Research Laboratory method. In addition to using the standard tests, ATP and 2,3 DPG levels and the viability of erythrocytes were also determined. RESULTS: The prefreezing mean viability rates of erythrocytes changed from 89.7 +/- 13.7% to 98.6 +/- 1.8% after thawing and deglycerolization. Prefreezing and day 0 ATP levels (1.64 +/- 0.15 umol/g Hb and 1.81 +/- 0.14 umol/g Hb, respectively) were similar. The 2,3-DPG levels decreased from 18.09 +/- 4.78 umol/g Hb measured before the procedure to 10.41 +/- 4.58 umol/g Hb on day 0. The mean hemolysis rates and supernatant Hb levels changed from 0.21 +/- 0.11% to 0.36 +/- 0.12% and 1 +/- 0.5 g/L to 1.5 +/- 0.5 g/L, respectively. CONCLUSION: The test results showed the efficacy of the frozen-thawed ECs to be used in humans for a broad spectrum of clinical indications. As a part of a contingency plan, national frozen blood reserves need to be established. PMID- 26281333 TI - Sp1 binding site polymorphism of a collagen gene (rs 1800012) in women aged 45 and over and its association with bone density. AB - BACKGROUND/AIM: Sp1 polymorphism of type I collagen genes is accompanied with bone collagen disorders and severe clinical phenotypes such as osteogenesis imperfecta. The aim of this study was to study the association between COLIA1 Sp1 polymorphism and bone density rate. MATERIALS AND METHODS: In this descriptive, analytical study conducted in 2013 in southwestern Iran, 200 blood samples, per the Cochran sample size formula, were taken from women aged 45 and older. DNA was extracted from the samples using the phenol-chloroform method and the genomic fragments in question were proliferated using the polymerase chain reaction (PCR) method. RESULTS: The genotype distribution of Sp1 polymorphism for the SS, Ss, and ss genotypes was 57.1%, 31.4%, and 11.4%, respectively, in the control group and 9.2%, 75.4%, and 15.4%, respectively, in the patients. Statistically, Sp1 polymorphism in patients had a significant deviation (P = 0.00 1, chi2 = 34.25) and there was no Hardy-Weinberg equilibrium. In the control group, there was no significant deviation for Sp1 polymorphism (P = 0.226, chi2 = 2.97). Sp1 polymorphism was significantly associated with bone density. Women with the SS genotype had the highest bone density. CONCLUSION: Sp1 gene polymorphism is associated with bone density rate in women aged 45 and over, and is more commonly observed in homozygosity. Determining this genotype's polymorphism is valuable to identify the women at risk of developing osteoporosis. PMID- 26281334 TI - Central corneal thickness in type II diabetes mellitus: is it related to the severity of diabetic retinopathy? AB - BACKGROUND/AIM: To compare the central corneal thickness (CCT) of type II diabetes mellitus patients with age- and sex-matched healthy subjects and to determine the association of the severity of diabetic retinopathy and CCT. MATERIALS AND METHODS: Type II diabetes mellitus patients without retinopathy, with nonproliferative retinopathy, and with proliferative retinopathy were organized as the three subgroups of the study group, and an age- and sex-matched control group was formed. All subjects underwent full ophthalmological examination and CCT measurement with ultrasonographic pachymetry. CCT values were compared between diabetic and healthy subjects and between the three diabetic subgroups. Correlation analysis was performed to determine any relationship between CCT and intraocular pressure. RESULTS: The average CCT was significantly higher in diabetic patients than in the control group (P = 0.04). CCT in diabetic patients without retinopathy did not significantly differ from that of patients with retinopathy (P = 0.64). Similarly, there was no significant difference in CCT between nonproliferative and proliferative diabetic retinopathy patients (P = 0.47). In the whole study population, CCT was significantly correlated with intraocular pressure (P < 0.01). CONCLUSION: CCT is significantly increased in type II diabetes mellitus patients with respect to controls. Retinal disease severity does not seem to have an effect on corneal thickness. PMID- 26281335 TI - High-risk febrile neutropenia and its management in children with solid tumors and lymphoma. AB - BACKGROUND/AIM: The clinical characteristics and treatment results of febrile neutropenia attacks that occurred in patients with lymphoma and solid tumors were analyzed. MATERIALS AND METHODS: A total of 50 patients with 94 high-risk attacks were evaluated for malignant diseases in this study. RESULTS: The fever etiology was determined as clinical (50%), microbiological (5.31%), clinical microbiological (5.31%), or unknown (39.3%). A few of the attacks (21.3%) were observed in lymphoma cases and 77.7% were observed in patients with solid tumors. Patients who were in remission had 59.6% of the attacks, and 39.4% occurred in patients not in remission. Among the groups tested, 73% (the imipenem/amikacin group) and 47.9% (the piperacillin-tazobactam/amikacin group) of patients were in remission. Glycopeptide addition rates in these groups were 22.2% and 40.8% and antifungal addition rates were 8.8% and 18.3%, respectively. CONCLUSION: Clinical progress was more problematic in patients who were not in remission during the attacks. This was due to the fact that some patients had other factors that placed them in the high-risk group, as well as increased C reactive protein and procalcitonin values on the first day. Therefore, it may not be accurate to associate the success achieved in the different treatment regimens with antibiotics alone. PMID- 26281336 TI - The hematologic manifestations of pediatric celiac disease at the time of diagnosis and efficiency of gluten-free diet. AB - BACKGROUND/AIM: To determine the hematologic manifestations at the time of diagnosis of celiac disease in children and the effects of a gluten-free diet on hematologic signs upon follow-up. MATERIALS AND METHODS: The records ofpatients with celiac disease who received a follow up examination at the Pediatric Gastroenterology Clinic between June 2006 and June 2013 were retrospectively examined. RESULTS: Ninety-one patients were included in the study. The mean age at diagnosis was 8.1 +/- 4.21 years and 59 patients (64.8%) were female. Thirty two patients (35.2%) had hematologic signs at the time of diagnosis. Anemia (24.2%) was the most common hematologic sign, followed by thrombocytosis (16.5%) and leukopenia (4.4%). The tTG IgA titers were screened in 80 of the 91 patients during diagnosis. Follow-up examinations found that remission for anemia (P = 0.0 17), thrombocytosis (P = 0.039), and decreases in tTG IgA titers (P = 0.034) were more prominent in patients who had followed a strict gluten-free diet. CONCLUSION: Approximately one-third of the celiac disease patients had hematologic manifestations at the time of diagnosis. Remission in hematologic signs and decrease in tTG IgA titers were more prominent in patients who had adhered to a gluten-free diet. PMID- 26281337 TI - Serologic testing for celiac disease in young people with elevated transaminases. AB - BACKGROUND/AIM: A cryptogenic elevation of transaminases is the most common hepatic manifestation in celiac disease (CD). In adult patients and pediatric patients with cryptogenic hypertransaminasemia, the prevalence of CD was 4% and 12%, respectively. However, there are no related data from China in this regard. We aimed to investigate the status of CD in young Chinese patients with elevated transaminases. MATERIALS AND METHODS: A total of 125 patients with elevated transaminases and 125 healthy individuals as controls with matched age and sex were involved in the study. Serum markers of hepatitis B were determined in patients with elevated transaminases. All subjects were screened for CD by testing serum IgA antitissue transglutaminase antibodies (anti-tTG IgA), and total serum IgA was determined in order to rule out IgA deficiency. RESULTS: None of the subjects were seropositive to IgA anti-tTG antibodies. No association between CD and elevated transaminases was found. Hepatitis B viral infections were one of the main causes of raised transaminases. CONCLUSION: Before the exclusion of every known cause of raised transaminase levels, routine serological screening for CD should not be recommended for patients who only present elevated transaminases. PMID- 26281338 TI - Evaluation of the effect of isotretinoin on salivary gland function by Tc-99m pertechnetate imaging in acne vulgaris patients. AB - BACKGROUND/AIM: Isotretinoin is an effective drug utilized in the management of acne vulgaris and is known to cause dry mouth. In this study, we aimed to evaluate this effect of isotretinoin on the salivary gland function in patients with acne vulgaris using technetium-99m (Tc-99m) pertechnetate imaging of the salivary glands. MATERIALS AND METHODS: The study population consisted of 28 patients with acne vulgaris (6 males and 22 females, mean age 20.2 +/- 2.3 years), who were treated with isotretinoin for 6 months. We performed radionuclide imaging of the salivary glands pretreatment and at months 3 and 6 of treatment. After 185 MBq (5 mCi) of Tc-99m pertechnetate was intravenously administered, imaging of the salivary glands was performed over a 25-min period. We measured the following glandular function parameters for the parotid and submandibular salivary glands via time-activity curves: uptake ratio, maximum accumulation, and ejection fraction. RESULTS: Statistically significant differences were observed in the values obtained at months 3 and 6 of treatment, compared with the pretreatment values. CONCLUSION: This study demonstrated that radionuclide imaging of the salivary glands can clearly show the glandular functions that are affected by drugs such as isotretinoin. PMID- 26281339 TI - Burnout in caregivers of patients with schizophrenia. AB - BACKGROUND/AIM: To evaluate the burnout of schizophrenia patients' caregivers and to determine the possible relationships between sociodemographic characteristics, symptomatology, perceived social support, and the burnout profile of the caregivers. MATERIALS AND METHODS: Subjects included in the study are 76 schizophrenia patients, diagnosed according to DSM-IV-TR criteria, and their caregivers. A sociodemographic form, the Scale for the Assessment of Positive Symptoms, and the Scale for the Assessment of Negative Symptoms were applied to evaluate the severity of the symptoms. The Maslach Burnout Inventory for Caregivers and the Multidimensional Scale of Perceived Social Support were applied to the caregivers of the patients. The collected data were analyzed via Student's t-test, one-way analysis of variance, and Pearson's correlation analysis. RESULTS: The burnout profile of the caregivers was highly correlated with the perceived social support of the caregivers and was also correlated with negative symptoms of the patients. Lower perceived social support was related to all subscales of the Maslach Burnout Inventory. CONCLUSION: Perceived social support is a major factor for caregiver burnout and it was highly correlated with all subscales in our study. We think that having social support provides caregivers with better feelings and so they provide better help to the patients. Appropriate approaches should be taken to intervene in the social and clinical factors that may exacerbate the burnout process. PMID- 26281340 TI - Efficacy of diffusion-weighted magnetic resonance imaging in the evaluation of extrahepatic cholestasis-related hepatic fibrosis. AB - BACKGROUND/AIM: To investigate the efficacy of diffusion-weighted magnetic resonance imaging (DWI) in the diagnosis and staging of fibrosis induced by experimental bile duct ligation (BDL). MATERIALS AND METHODS: Twenty-four rats were divided randomly into four groups: control, BDL--3 days, BDL--2 weeks, and BDL--4 weeks. DWI was performed with b-values of 100 and 500 on the rats from control group at day zero, on the rats from the BDL--3 days group at the end of day 3, on the rats from the BDL--2 weeks group at the end of day 14, and on the rats from the BDL--4 weeks at the end of day 28. RESULTS: When fibrosis scores generated in all groups were evaluated together, a strong negative correlation was detected between fibrosis scores and apparent diffusion coefficient (ADC) values measured using b 100 and b 500. ADC values obtained using b 100 were found to be significantly higher compared to the fibrosis observed in both the BDL--2 weeks and BDL--4 weeks groups (P < 0.003 and P < 0.001, respectively). CONCLUSION: We think that DWI may be an alternative to liver biopsy for the diagnosis and staging of hepatic fibrosis with underlying extrahepatic cholestasis. PMID- 26281341 TI - Comparison of local infiltration anesthesia and peripheral nerve block: a randomized prospective study in hand lacerations. AB - BACKGROUND/AIM: To compare local infiltration anesthesia (LIA) and peripheral nerve block (PNB) in repairing hand lacerations. MATERIALS AND METHODS: This prospective study was designed as a randomized, controlled, unblinded trial. Fifty four patients with hand lacerations were included in the study. While 23 of these patients had LIA, PNB was performed in the remaining 31 patients. Lidocaine hydrochloride 2% and 27 gauge needles were used. Onset time of the anesthesia, response to the injection and suturing procedures, need for additional anesthetic, and patient satisfaction were compared. RESULTS: No significant differences were noted between the groups in terms of response to injection pain and suture pain (Mann-Whitney U; P = 0.220/P = 0.316). There were also no significant differences between the groups when patient satisfaction (chi-square; P = 0.785) and need for additional local anesthetics (Fisher's exact; P = 0.628) were evaluated. The time to loss of pinprick sensation in the local infiltration group was 1.3 min, whereas in the nerve block group it was 2.2 min. The difference was statistically significant (Mann-Whitney U; P < 0.001). CONCLUSION: Despite the fact that performing PNB in emergency departments requires some experience, it still counts as a convenient method comparable to LIA. PMID- 26281342 TI - Efficacy of wound infiltration with lornoxicam for postoperative analgesia following thyroidectomy: a prospective, randomized, double-blind study. AB - BACKGROUND/AIM: Postoperative pain control constitutes a major problem and studies have focused on reducing opioid requirements using regional techniques. We aimed to investigate the efficacy of wound infiltration with lornoxicam on postoperative pain control following thyroidectomy. MATERIALS AND METHODS: In this prospective, randomized-controlled study, 80 patients scheduled for thyroidectomy were randomly assigned to 2 groups. After the thyroidectomy was performed, patients in group I underwent wound infiltration with 4 mg of lornoxicam and patients in group II received the same amount of saline. Rescue analgesia was provided with additional doses oflornoxicam delivered by an on demand patient-controlled analgesia device. Total analgesic consumption during the postoperative 24 h, and pain intensities assessed using a visual analog scale score at 0, 2, 4, 8, 12 and 24 h postoperatively were recorded. RESULTS: Pain scores during the postoperative 24 h were slightly lower in group I than in group II, but the difference was not significant (P > 0.05). The mean analgesic consumption was 8.87 +/- 1.87 mg and 10.33 +/- 1.25 mg in groups I and II, respectively (P > 0.05). CONCLUSION: Wound infiltration with lornoxicam neither improved postoperative pain control nor decreased total analgesic consumption. PMID- 26281343 TI - Comparison of endometrial biopsies of fertile women and women with repeated implantation failure at the ultrastructural level. AB - BACKGROUND/AIM: The aim of this study was to compare the cellular properties of endometrial tissues from fertile patients and patients having at least 3 previous in vitro fertilization failures, during the implantation window. The ultrastructural evaluation of the endometrium in the implantation window may shed light on the complexity of the implantation failure paradigm. MATERIALS AND METHODS: The study involved 23 women, 14 infertile with a clinical diagnosis of repeated implantation failure (RIF) and 9 fertile, defined as the control group. Endometrial samples were examined by transmission electron microscopy (TEM). RESULTS: In the control group, secretory vacuoles and cytoplasmic projections filled with secretory material, called pinopodes, were noted; microvilli were observed on some apical surfaces; and ciliated cells were absent. In the RIF group, the number of pinopodes was remarkably lower, with some of them being immature. Moreover, decidualization of stromal cells was not frequent and fewer epithelial cells with poor secretory vacuoles were discerned. CONCLUSION: TEM analyses of endometrial samples from the RIF group revealed dramatic differences at the ultrastructural level compared to the controls, which may well be an underlying cause of their infertility. PMID- 26281344 TI - Fetal health locus of control in a sample of pregnant Turkish women. AB - BACKGROUND/AIM: To examine the relationship between sociodemographic and pregnancy features and fetal health locus of control (FHLC) in a sample of pregnant Turkish women. MATERIALS AND METHODS: The study was conducted with 256 pregnant women. Data were collected by demographic questionnaire and the FHLC Scale consisting of 3 components: 1) Internality Scale (FHLC-I), 2) Powerful Others Scale (FHLC-P), and 3) Chances Scale (FHLC-C). RESULTS: The age of marriage was found to have a positive relation with FHLC-I (r = 0.141) and a negative relation with FHLC-C (r = -0.145) (P < 0.05). The age of first pregnancy was found to have a positive relation with FHLC-I (r = 0.127). Those who have a low educational level (r = -0.258) and income (r = -0.149), who are unemployed (r = -2.839), whose number of pregnancies is high (r = 0.152), who get pregnant unplanned (r = 3.839), and who come to their first prenatal examination late (r = -0.142) have a significantly high score of FHLC-C (P <0.05). CONCLUSION: It may be helpful for better outcomes of prenatal care to identify pregnant women who believe that their behavior has little effect on the health of their fetus and that it is controlled by chance. PMID- 26281345 TI - Intrahepatic cholestasis of pregnancy may lead to low birth weight. AB - BACKGROUND/AIM: To evaluate patients hospitalized in our clinic in the last 5 years with the diagnosis of intrahepatic cholestasis of pregnancy (ICP). MATERIALS AND METHODS: One hundred and fifty patients hospitalized with a diagnosis of ICP between January 2008 and May 2013 were evaluated retrospectively and age, week at diagnosis, gestational age at delivery, period between diagnosis and delivery, fetal weight, transaminases, and coagulation parameters were recorded. Patients were divided into groups according to their diagnosis weeks and gravida. Accordingly, patients diagnosed before 32 weeks formed group A (n = 49) and those after 32 weeks formed group B (n = 101). Data were evaluated with SPSS 16.0. RESULTS: There was a significant difference between group A and group B in terms of delivery period and fetal weights (P = 0.001, P 0.035). Accordingly, the period between diagnosis and delivery and fetal weight were found to be longer and lower, respectively, in the early-onset group. In terms of distribution of ICP according to time of diagnosis, patients were diagnosed mostly in the spring season (60 cases, 40%) and in the month of March (27 cases, 18%). CONCLUSION: According to our study, the birth weight of fetuses of patients with ICP diagnosed before 32 weeks are lower, although they have the same gestational age at delivery as the fetuses of the patients with ICP diagnosed after 32 weeks. PMID- 26281346 TI - Human semen quality and sperm DNA damage assessed by comet assay in clinical groups. AB - BACKGROUND/AIM: About 10%-15% of couples around the world suffer from infertility. Male infertility is responsible directly or indirectly in approximately 60% of cases. A deficiency in semen is the most common cause of male infertility. MATERIALS AND METHODS: The study included 180 male subjects aged 18-50 years with 26 fertile and 154 infertile. The infertile subjects were further subdivided according to the WHO guidelines of semen analysis (2010) into different clinical groups. Sperm DNA damage was estimated using a neutral comet assay. Plasma gonadotropin and testosterone levels were measured using a chemiluminescence assay. RESULTS: The results of the study revealed no significant differences, in semen volume, pH, and liquefaction time between the fertile and all infertile groups. However, sperm concentration, sperm vitality, and sperm motility were significantly lower in all infertile groups as compared to the fertile males. The morphological forms of the sperm and its DNA fragmentation varied significantly between the fertile and infertile males. Reproductive hormone levels were observed to be significantly lower in the infertile than in the fertile males. CONCLUSION: Sperm DNA fragmentation was higher in all of the infertile subjects as compared to the fertile ones. Reproductive hormone levels varied significantly between the infertile patients and the fertile ones. PMID- 26281347 TI - Suspension of Arthroderma and Trichophyton species in RPMI-1640 medium provided long-term viability at room temperature. PMID- 26281348 TI - Distribution and antifungal resistance of Candida species isolated from intensive care units. PMID- 26281349 TI - Myelodysplastic features and cellular senescence in autoimmune disorders: a pilot study on patients with collagen tissue disorders and immune thrombocytopenic purpura. PMID- 26281350 TI - [Molecular therapeutic strategies for Huntington's disease]. AB - Huntington's disease is a progressive neurodegenerative disorder of genetic origin that still lacks an effective treatment. Recently, a number of new attempts have been undertaken to develop a successful molecular therapy for this incurable condition. The novel approaches employ, among others, some new methods to selectively silence the mutated gene or to neutralize its toxic protein product. This paper reviews all major strategies that are currently considered for molecular therapy of Huntington's disease while discussing their potential effectiveness regarding the treatment of both the Huntington's disease and a large group of related neurodegenerative disorders associated with abnormal protein aggregation. PMID- 26281351 TI - [Angiogenesis - possibilities, problems and perspectives]. AB - Angiogenesis is the formation of new blood vessels from existing vessels. This process occurs via budding endothelial cells in postnatal period, which is essential to many physiological phenomena (e.g. wound healing, formation of the placenta) and pathological ones such as cancer, ischemic diseases, and chronic inflammation. Various mechanisms of the formation of new blood vessels have been discovered and a number of pro-angiogenic and anti-angiogenic factors have been found. Understanding the function of these factors contributes to the creation of new tools and applications in the treatment of pathological processes. Article describes the regulation of angiogenesis and is a review of the most significant angiogenic factors and their inhibitors. It shows the selected mechanisms which underlie the action of currently used anti-angiogenic drugs and is a review of research which use these factors in anti-angiogenic therapy. PMID- 26281352 TI - [Torsin 1A and the pathomechanism of torsion dystonia type 1]. AB - Torsin 1A is a protein mutated in torsion dystonia type 1, a hereditary neurological disorder of early onset and variable clinical picture. The basic cellular function of torsin 1A, a polypeptide localized predominantly in the endoplasmic reticulum and nuclear envelope, remains unknown, although the protein is suspected of being involved in many different cellular processes, including regulating a proper structure and function of nuclear envelope, contributing to the synaptic vesicular trafficking, or assisting in proper folding of misfolded proteins. This review summarizes the current state of knowledge regarding the potential functions of torsin 1A in the context of hypothetical pathomechanisms responsible for torsion dystonia type 1. PMID- 26281353 TI - [Multifunctionality of MDM2 protein and its role in genomic instability of cancer cells]. AB - Numerous studies have revealed that MDM2 oncoprotein is upregulated in different types of cancer. Additionally, it was demonstrated that in some cases, MDM2 may inhibit the neoplastic transformation process. In other words, MDM2 protein can be considered as an oncogene or as a tumor suppressor depending on the appropriate cellular context. MDM2 functions on different levels in the cell, which is a consequence of its complex structure, a plethora of interacting partners and regulation through numerous postranslational modifications. Thus, an alteration of the delicate balance in MDM2 activity can influence transformation and cancer development. Genomic instability is a hallmark of cancer, which inversely correlates to the activity of DNA damage response. In the case of not transformed cells MDM2 inhibits double strand brakes (DSBs) repair, hence stimulating carcinogenesis. In cancer cells MDM2 stimulates cytostatic-induced DSBs repair, thus leading to chemoresistance. PMID- 26281354 TI - [GPER receptor - the new player in estrogen signaling]. AB - Recent studies reveal that estrogens act on cells and tissues, not only through two canonical estrogen receptors ERalpha and ERbeta, but also through the receptor coupled with G proteins, named GPER, formerly GPR30, and member of seven transmembrane receptor superfamily. GPER was found to be implicated both in rapid non-genomic estrogen response and in transcriptional regulation. Effects of GPER include activation of MAPK and PI3K signaling pathways, stimulation of adenyl cyclase, and mobilization of calcium ions from intracellular stores, as well as upregulation of genes such as FOS and CTGF. Identification of agonists and antagonists of GPER allowed not only to shed light on the participation of estrogen signaling in the biology and pathobiology of hormone-dependent tissues, but also its importance in the estrogen and antiestrogen therapies. Antiestrogens tamoxifen, raloxifene, or fulvestrant proved,to be agonists of GPER, which undoubtedly is not without significance for the efficacy of the therapy. PMID- 26281355 TI - [Cytokinins and photosynthesis]. AB - Almost six decades of studies explained many aspects of cytokinin complex metabolism, such as, biogenesis, degradation, signal perception and interaction with other phytohormones (mainly with auxins). A dual character of cytokinins' action on the nuclear genes (activation and repression) has been explained by recognition of the two types on nuclear receptors, which ensure a precise mechanism of self-control. Cytokinins promote the process of photosynthesis at different levels of plant- and cellular organization (development of leaves and plastids, influence on the photosynthetic proteins, activation of photosynthetic genes, etc.). An anti-senescing action of these hormones has been recently attributed to the activation of intra-cellular invertase, which suppress floem loading and change the sink-source pattern of the leaf. PMID- 26281356 TI - [Acyltransferases involved in plant secondary metabolism: classification, structure, reaction mechanism]. AB - Acyltransferases'participate in many metabolic pathways in plants, especially in secondary metabolism pathways. These enzymes catalyse transfer of an acyl group from energy-rich donor molecule to nucleophilic group of an acceptor molecule resulting in ester bond formation. Plant acyltransferases can be divided into two families: serine carboxypeptidase-like acyltransferases (SCPL) and BAHD acyltransferases (named after its first four characterized enzymes). Based on differences in substrate specificity and aminoacid sequence, BAHD acyltransferas es have been classified into five clades. SCPL acyltransferases utilise energy rich 1-O-beta-D-glucose esters as donors of an acyl group, instead of coenzyme A thioesters, which are substrates for acyltransferases from more abundant BAHD family. SCPL acyliransferases are homologous to hydrolases from serine carboxypeptidases family. They share some structural elements, such as conserved catalitic triad or alphabeta hydrolase fold. PMID- 26281357 TI - [Plant signaling peptides. Cysteine-rich peptides]. AB - Recent bioinformatic and genetic analyses of several model plant genomes have revealed the existence of a highly abundant group of signaling peptides that are defined as cysteine-rich peptides (CRPs). CRPs are usually in size between 50 and 90 amino acid residues, they are positively charged, and they contain 4-16 cysteine residues that are important for the correct conformational folding. Despite the structural differences among CRP classes, members from each class have striking similarities in their molecular properties and function. The present review presents the recent progress in research on signaling peptides from several families including: EPF/EPFL, SP11/SCR, PrsS, RALF, LURE, and some other peptides belonging to CRP group. There is convincing evidence indicating multiple roles for these CRPs as signaling molecules during the plant life cycle, ranging from stomata development and patterning, self-incompatibility, pollen tube growth and guidance, reproductive processes, and nodule formation. PMID- 26281358 TI - [Cathelicidins - endogenous antimicrobial peptides]. AB - Within the last decade, several antimicrobial peptides (AMPs) have been discovered. Cathelicidins are one family of AMPs characterized by a conserved cathelin domain and a variable C-terminal cationic antimicrobial domain. These peptides are produced by different cells, including leukocytes, epithelial cells and keratinocytes. Besides their direct antimicrobial function, cathelicidins can also regulate the course of inflammation and influence the mechanisms of innate immunity. In this review we discuss the biology of animal cathelicidins, their structure, expression and function. PMID- 26281359 TI - [Arabidopsis thaliana accessions - a tool for biochemical and phylogentical studies]. AB - Arabidopsis thaliana since a few decades is used as a model for biological and plant genetic research. Natural variation of this species is related to its geographical range which covers different climate zones and habitats. The ability to occupy such a wide area by Arabidopsis is possible due to its stress tolerance and adaptability. Arabidopsis accessions exhibit phenotypic and genotypic variation, which is a result of adaptation to local environmental conditions. During development, plants are subjected to various stress factors. Plants show a spectrum of reactions, processes and phenomena that determine their survival in these adverse conditions. The response of plants to stress involves signal detection and transmission. These reactions are different and depend on the stressor, its intensity, plant species and life strategy. It is assumed that the populations of the same species from different geographical regions acclimated to the stress conditions develop a set of alleles, which allow them to grow and reproduce. Therefore, the study of natural variation in response to abiotic stress among Arabidopsis thaliana accessions allows to find key genes or alleles, and thus the mechanisms by which plants cope with adverse physical and chemical conditions. This paper presents an overview of recent findings, tools and research directions used in the study of natural variation in Arabidopsis thaliana accessions. Additionally, we explain why accessions can be used in the phylogenetic analyses and to study demography and migration of Arabidopsis thaliana. PMID- 26281361 TI - Questions Answered about RightSize Dental Plan. PMID- 26281360 TI - Governor Proposes HKD, Adult Dental Expansion in 2016 Budget Request. PMID- 26281362 TI - Make Your Annual Session Plans Now! PMID- 26281363 TI - State Program Provides Student Loan Relief; Deadline Coming Soon. PMID- 26281365 TI - Support the MDA Dental PAC 2015 Action Campaign. PMID- 26281364 TI - New MDA Public Education Campaign Off to Good Start. PMID- 26281366 TI - MDA Journal Goes Digital! Current Issue Now Posted Online. PMID- 26281367 TI - ADA Expert to Discuss Dentistry's Future. PMID- 26281368 TI - Benefit of the Month: COVER Program. PMID- 26281369 TI - Reminder: MDA Offers CE Tracking. PMID- 26281370 TI - Postal Service: Mail Delivery Will Be Slower in Michigan. PMID- 26281372 TI - MDA Seeking Volunteers for Michigan Mobile Smile Link Directory. PMID- 26281373 TI - MDA Visa Card Program Lets You Earn Cash Back. PMID- 26281374 TI - Get High-limit Disability Insurance without Medical Exam. PMID- 26281375 TI - Legislative Advocacy: Get Involved! PMID- 26281376 TI - Is It Legal to Have More than One Fee Schedule? PMID- 26281371 TI - Macomb Half-Day Seminar Coming to Warren March 20. PMID- 26281377 TI - A Culture of Respect: Little Things Can Make a Big Difference. PMID- 26281378 TI - 'Cooking the Books' Redux. PMID- 26281379 TI - JADA Publishes an Important Re-analysis of the Evidence Behind Delta's RightSize Plan. PMID- 26281380 TI - Capitol Outlook 2015. What's Ahead for Dentistry in Lansing. PMID- 26281381 TI - MDA Grass Roots Legislative Program: Easy, Fun and Very Important! PMID- 26281382 TI - Foreign Body Gingivitis. AB - Foreign body gingivitis (FBG) is a non-plaque induced chronic inflammatory process involving the marginal and/or attached gingiva. It results from the introduction of foreign particulate material, primarily dental prophylaxis paste and restorative dental materials, into the gingival tissues. Clinical presentation varies from an erythematous to vesiculoerosive-like process that may mimic a localized form of desquamative gingivitis or an erosive lichenoid process. Rarely, it may also present with a granular appearance. We describe the clinical presentation, differential diagnosis and clinical management of a 52 year-old Woman who presented with localized chronic inflammation of the maxillary anterior and left posterior gingiva secondary to the presence of foreign material. PMID- 26281383 TI - Insurance Changes--Buyer Beware (and Be Informed). The Potential Impact of Third Party Administrators. PMID- 26281384 TI - Dr. Donald French Honored with 2014 Silent Bell Award. PMID- 26281385 TI - Fall Protection for Iron Workers. PMID- 26281386 TI - The ABCs of Personal Fall Arrest Systems. PMID- 26281387 TI - Heads Up! PMID- 26281388 TI - The Ripple Effect of Missed GHS Deadlines. PMID- 26281389 TI - Hazmat Identification, Control, and Emergency Response: The Fundamental Weakness in the System. PMID- 26281390 TI - Three Hazmat Rules Every Employee Can Remember. PMID- 26281391 TI - The MoreThings Change.... PMID- 26281392 TI - OSHA-Related Documents: Creation and Retention. PMID- 26281393 TI - Plan, Prepare and Recover: How Businesses Can Manage Through Emergencies. PMID- 26281394 TI - OSHA's New Confined Space Standard. PMID- 26281395 TI - Adult Learning Principles for Safety Training. PMID- 26281396 TI - The Scary Thing About Safety Training. PMID- 26281397 TI - Coordinating Guidelines and the ANSI Z358.1 Standard. PMID- 26281398 TI - What Were You Thinking? The Key to Communicating More Effectively. PMID- 26281399 TI - Climate and Culture Before, Not After, Behavior-Based Safety. PMID- 26281400 TI - Curing Cultural Cancer? PMID- 26281401 TI - Nursing: the answer to the primary health care dilemma. PMID- 26281402 TI - Rainbows: a primary health care initiative for primary schools. AB - Within the current Australian health system is the understanding of a need to change from the predominate biomedical model to incorporate a comprehensive primary health care centred approach, embracing the social contexts of health and wellbeing. Recent research investigated the benefits of the primary health care philosophy and strategies in relation to the Rainbows programme which addresses grief and loss in primary school aged students in Western Australia. A multidisciplinary collaboration between the Western Australian Departments of Health and Education enabled community school health nurse coordinators to train teacher facilitators in the implementation of Rainbows, enabling support for students and their parents. The results of this qualitative study indicate that all participants regard Rainbows as effective, with many perceived benefits to students and their families. PMID- 26281403 TI - Nursing students' intentions to enter primary health care as a career option: Findings from a national survey. AB - This paper reports findings from the first phase of a national study conducted to identify the intention of nursing students' to work in a Primary Health Care setting following registration. An online survey of final year nursing students enrolled at Australian universities offering education leading to eligibility for registration as a nurse with the Australian Health Practitioner Regulation Agency was undertaken during July-August 2014. Data were collected about students' intention to enter Primary Health Care as a career option, as well as their exposure to primary health care during their nursing education and whether they had undertaken practice placements in a primary health care setting. Analysis was conducted on 456 completed surveys. The findings demonstrated that, despite the majority (98.2%; n = 447) of students being exposed to Primary Health Care during their studies, less than a quarter (22.8%; n = 104) of the students who responded identified this as an area in which they intended to work following registration. No association was found between students' clinical experiences and their identification of primary health care as a career preference. Given the ageing population in Australia, the increased prevalence of chronic health issues and the predicted ongoing primary health care workforce shortages, educational and workplace strategies aimed at attracting new graduate nurse into Primary Health Care settings are imperative. PMID- 26281404 TI - The nurse practitioner role: Solution or servant in improving primary health care service delivery. AB - In New Zealand, as in many other countries, the demand for health services is escalating as chronic disease, population ageing and health disparities increase. It has been argued that a more comprehensive primary health care approach is needed combining biomedical approaches with a social determinants and social justice based approach. The contemporary development of the nurse practitioner (NP) role in New Zealand (NZ) offers the possibility of taking up a more critical approach to strengthen and extend primary health care services (PHC). Nurse practitioners could simply be utilised to shore up the nature and style of existing primary care (PC) service configurations or, more usefully, they could lead a revolution in traditional approaches towards genuine primary health care delivery. PMID- 26281405 TI - Nursing students' experiences of clinical placement in community settings: a qualitative study. AB - BACKGROUND: Changing community demographics and the rising incidence of chronic and complex conditions has exacerbated the primary care workload. Encouraging beginning nurses to view primary care nursing as a viable career option will help alleviate the workforce stress of this specialty. Whilst higher education institutions (HEI's) have increased the exposure of pre-registration nurses to community settings, there has been limited exploration of this experience from the perspective of pre-registration nurses. As potential key service providers, it is important to identify factors which influence how pre-registration nurses view primary care placements in the community. AIM: This study seeks to explore the experiences of pre-registration nursing students following community based clinical placements and to explore the impact of this placement on their learning. DESIGN: A qualitative design was employed in this study. PARTICIPANTS: Nine pre-registration nursing students were recruited from a research intensive single campus of an Australian university. METHODS: In-depth semi-structured interviews. FINDINGS: Findings are presented in the following four themes: (1) autonomy in practice: "you make your own decisions", (2) working with highly skilled nurses: "their knowledge was just incredible", (3) focusing on holistic care: "they'd obviously built rapport with these people", and (4) showing genuine interest in educating students: "they got me involved". CONCLUSION: Exposure to community settings was a positive learning experience for pre-registration nursing students. Further research needs to focus on the impact of these placements on both clinical skills acquisition and job choices into the future. PMID- 26281406 TI - An investigation of barriers and enablers to advanced nursing roles in Australian general practice. AB - Over the past decade, there has been substantial increase in nurses' roles in primary health care, particularly in general practice settings. Simultaneously, there has been an expansion of advanced roles for nurses across a range of clinical environments. This paper draws upon findings from a study that sought to develop a framework to support development of advanced nursing roles in general practice. It presents findings from one part of that study that explored barriers and facilitators to the development of these roles. Twenty-three key leaders from nursing, general practice and professional organisations participated in semi structured interviews. Data were analysed using thematic analysis. A range of factors was identified as key to developing advanced roles in general practice. These included increasing awareness and attractiveness of practice nursing, health reform activities, practice limitations, education and professional development. Understanding complex systems and workforce issues is required to promote active intervention that can facilitate development of advanced nursing roles in Australian general practice. PMID- 26281407 TI - Building chronic disease management capacity in General Practice: The South Australian GP Plus Practice Nurse Initiative. AB - AIM: This paper draws on the implementation experience of the South Australian GP Plus Practice Nurse Initiative in order to establish what is needed to support the development of the chronic disease management role of practice nurses. BACKGROUND: The Initiative was delivered between 2007 and 2010 to recruit, train and place 157 nurses across 147 General Practices in Adelaide. The purpose was to improve chronic disease management in General Practice, by equipping nurses to work as practice nurses who would coordinate care and establish chronic disease management systems. METHOD: Secondary analysis of qualitative data contained in the Initiative evaluation report, specifically drawing on quarterly project records and four focus groups conducted with practice nurses, practice nurse coordinators and practice nurse mentors. FINDINGS: As evidenced by the need to increase the amount of support provided during the implementation of the Initiative, nurses new to General Practice faced challenges in their new role. Nurses described a big learning curve as they dealt with role transition to a new work environment and learning a range of new skills while developing chronic disease management systems. Informants valued the skills development and support offered by the Initiative, however the ongoing difficulties in implementing the role suggested that change is also needed at the level of the Practice. While just over a half of the placement positions were retained, practice nurses expressed concern with having to negotiate the conditions of their employment. CONCLUSION: In order to advance the role of practice nurses as managers of chronic disease support is needed at two levels. At one level support is needed to assist practice nurses to build their own skills. At the level of the Practice, and in the wider health workforce system, support is also needed to ensure that Practices are organisationally ready to include the practice nurse within the practice team. PMID- 26281408 TI - Satisfaction and comfort with nursing in Australian general practice. AB - The practice nursing workforce has grown exponentially in recent years. Whilst evidence has shown the important contributions of nurses to general practice service delivery, the consumer perspective of nursing in general practice has received limited attention. Given that acceptability of nurses is influenced by patient satisfaction which can in turn improve both treatment adherence and clinical outcomes, this is an important area for investigation. The primary aim of this study was to evaluate consumer satisfaction with chronic disease management by nurses in general practice (NiGP) and comfort with the tasks undertaken by nurses in general practice. Consumers receiving chronic disease services from nurses in general practice participating in a larger study were recruited to complete a survey. The survey comprised of demographic information, and items related to satisfaction with the nurse encounter (SPN-9) and consumer comfort with nurse roles in general practice (CPN-18). Eighty-one consumers participated in the study. Cronbach's alpha values of the SPN-9 and the CPN-18 were 0.95 and 0.97 respectively. SPN-9 results demonstrated high levels of satisfaction with PN consultations. Bivariate analysis did not show any significant differences within the consumer group relating to satisfaction. However, those who presented for diabetes-related reasons were more likely to report high comfort levels with the nurse encounter compare to those who presented to general practice for other chronic disease conditions (38% versus 14%, p = 0.016). The results of this study demonstrate that consumers are generally satisfied with nursing consultations in general practice related to chronic disease. However, further research evaluating consumer confidence, comfort and satisfaction with nursing care is needed to ensure that nursing services meet consumer needs. PMID- 26281409 TI - Impact of nursing care in Australian general practice on the quality of care: A pilot of the Patient Enablement and Satisfaction Survey (PESS). AB - BACKGROUND: Nursing roles in general practice have undergone significant expansion, but as yet there are few tools to measure the quality of nursing care in general practice. This study piloted the Patient Enablement and Satisfaction Survey (PESS) to evaluate two aspects of quality of care in this setting. METHODS: Participants were patients attending nurse-led general and chronic disease clinics in two general practices The survey was posted to 180 consecutive patients attending these clinics over one week (response rate, 28% for general clinic, 40% chronic diseases clinic; n = 57). Scores were calculated for enablement and satisfaction and free text comments were analysed. Comparisons were made between patients who had attended the general clinic for influenza vaccination and for other conditions, and those who attended the chronic diseases clinic. FINDINGS: Overall results indicate high levels of satisfaction (M = 68.3/75 SD = 8.1) and moderate enablement (M = 4.7/8 SD = 3.2). Significant differences were observed between satisfaction scores for patients attending the chronic disease clinic and the general clinic for influenza vaccinations alone, and between those attending the general clinic for influenza vaccinations versus treatment of other conditions. Patients attending the chronic disease clinic had higher enablement scores than patients receiving influenza vaccinations at the general clinic. Analysis of free-text comments in the survey supported these findings. CONCLUSION: All patients reported satisfaction with nursing care. Patients receiving chronic disease management reported high levels of enablement. This pilot indicated that the PESS can distinguish between two aspects of the quality of nursing care that may impact on patient outcomes. PMID- 26281410 TI - Health-promoting lifestyles and cardio-metabolic risk factors among international students in South Korea. AB - This study examined the health-promoting lifestyles and cardio-metabolic risks among international students in Korea. This descriptive, cross-sectional study design enrolled a convenience sample of 118 international students at a university in Korea. Collected data included items from the Health-promoting Lifestyle Profile (II) scale and cardiovascular risk factors. The participants had a moderately health-promoting lifestyle (2.5 of 4). Men engaged in more physical activity than did women (p = .002). The most prevalent risk factor was elevated blood lipid profiles (26.3%), followed by overweight/obesity (25.4%), elevated blood pressure (17.8%), and elevated fasting glucose levels (5.1%). More than half of the participants (54.2%) had one or more cardiac risk factors, and these participants also scored lower in health-promoting lifestyle factors than other students (p = .034). Regular health check-ups are needed to identify the cardio-metabolic risks of international students. A university-based programme aimed at promoting healthy lifestyles could help prevent cardio-metabolic risks among international students. PMID- 26281411 TI - Trust and decision-making: How nurses in Australian general practice negotiate role limitations. AB - AIM: To explore the importance of role recognition and relationships between the opportunities for decision-making, social support, and skill development, in a sample of nurses working in general practice in New South Wales, Australia. BACKGROUND: Understanding how nurses make decisions about patients and their care in general practice will benefit organisations and public policy. This understanding is important as the role changes and opportunities for further role development emerge. DESIGN: A sequential mixed methods design was used. Study 1 utilised the internationally validated Job Content Questionnaire to collect data about decision making, social support, skill development, and identity derived from the role. In 2008 a purposive sample of nurses working in general practice (n = 160) completed and submitted an online Job Content Questionnaire. Study 2 used a set of open-ended questions informed by Study 1 to guide semi-structured interviews. In 2010 fifteen interviews were undertaken with nurses in general practice. Demographic characteristics of both samples were compared, and the findings of both studies were integrated. RESULTS: The integration of findings of Study 1 and 2 suggests that nurses defined their expertise as being able to identify patient need and communicate this to the general practitioner, the ability to do so led to the development of trusting relationships. Trusting relationships led to greater support from the general practitioner and this support allowed the nurse greater freedom to make decisions about patient care. CONCLUSIONS: Nurses gained influence in clinical decision-making by building trusting relationships with patients and medical colleagues. They actively collaborated in and made decisions about patient care. These results suggest that there is a need to consider how nursing can more effectively contribute to care in general practice settings. PMID- 26281412 TI - Feasibility, acceptability and safety of a nurse led hepatitis B clinic based in the community. AB - AIM: The aim of this study was to investigate if a community based hepatitis B (HBV) nurse clinic is a feasible, acceptable and safe strategy to improve access to best practice chronic hepatitis B care (CHB) in Sydney Local Health District. METHODS: The weekly clinic commenced in an Inner West Sydney Health Centre in November 2012. The CNC responsibilities included patient assessment, management, education, triage, the development of care plans for GPs and GP support. Nursing practice was guided by recommendations from internationally and nationally endorsed CHB Guidelines. Information on patient demographics, clinical findings, triage decisions and sources of referral were collected and used to assess the feasibility, acceptability and safety of the nurse clinic. Patients were also invited to complete a self-administered survey. The survey included questions on attitudes towards the clinic and opinions on barriers to accessing treatment and care. Data was collated and analysed in both Excel and SPPS. RESULTS: In the first 18 months of the clinic 66 people attended, 56 (80%) had CHB, 51 (77%) were born in an Asian country. An equal number of males and females attended. 11 (17%) required further management at a hospital based liver clinic and were referred. 5 (8%) have commenced anti-viral treatment. 24 (36%) met the criteria for six monthly HCC screening and were commenced on HCC surveillance. Twenty-two GPs referred patients. 11 (17%) patients returned the survey and they reported a high level of satisfaction with the clinic and willingness to engage in future CHB care. CONCLUSIONS: This study of a community based CHB nurse clinic shows it is a feasible, acceptable, and safe initiative. The nurse improved access to best practice care and supported patients to effectively manage their CHB. We have confirmed a nurse can have a central role in triage, case management and GP support. Given the high CHB prevalence in our LHD a higher number of GP referrals were expected. Further research on how to increase engagement with GPs and people living with CHB is needed. We plan to expand our model with the CHB nurse conducting assessments and education in GP practices. PMID- 26281413 TI - President's 'proud moment' shared. PMID- 26281414 TI - The life and death of heating efficiency. PMID- 26281417 TI - Controlling humidity for healthier hospital. PMID- 26281416 TI - A strategic approach in Scotland outlined. PMID- 26281420 TI - Transformational change called for. PMID- 26281421 TI - Washroom safety in the spotlight. PMID- 26281415 TI - Hospitals single-room design evaluated. PMID- 26281422 TI - Anti-ligature: striking the right balance. PMID- 26281423 TI - Systems keeping up with latest technology. PMID- 26281419 TI - Search for efficiency savings continues. PMID- 26281418 TI - Importance of regular inspection stressed. PMID- 26281425 TI - Switchgear project meticulously managed. AB - Electrical engineering and estates personnel at Sodexo--which manages a wide range of soft and hard facilities management services for five hospitals under a PFI contract at the Manchester Royal Infirmary--have successfully planned, managed, and co-ordinated, a complex electrical engineering project which saw high voltage (HV) switchgear in the site's main intake sub-station dismantled by the supplier to repair a potential earthing mechanism fault which would have prevented individual switchgear panels being shut down, to, for example, cater for renovation of electrical cabling or components cross the site's high voltage network. With detailed planning, including provision for bringing onto site temporary bulk generators, and the formulation of a 600-step switching programme, the replacement of potential faulty driver components in the disconnect mechanism for 20 HV switchgear panels was completed in just four weeks, with minimal interruption to the vast complex's power supply. PMID- 26281424 TI - Concerted drive to cut carbon footprint. AB - In 2013 Peter Sellars, head of Profession for Estates & Facilities Policy at the Department of Health, successfully bid for L50 million from the Treasury to help finance a range of 'spend-to-save' energy efficiency initiatives across the NHS in England. In all 117 energy efficiency projects were initiated across 48 English NHS organisations--funded through a dedicated NHS Energy Efficiency Fund. An independent analysis for the DH, NHS Energy Efficiency Fund Final Report, Summary 2014, by Professor Alan Short of Cambridge University's Department of Architecture, says the projects are already on track to save 100.6 million kg of CO2 annually, and some 2.4% of the entire 2012 NHS building energy-related carbon footprint, delivering annual energy savings of 160.5 million kWh (equivalent to boiling 3.34 billion cups of tea a year.) The Report--reproduced in large part here--summarises the schemes' preliminary outcomes, and makes recommendations for policy-makers implementing similar energy-saving funding schemes in the future. PMID- 26281426 TI - Correct sizing decisions key to success. AB - According to specialist in optimised resource management, Veolia, combined heat and power (CHP) 'has been proven for its effectiveness in reducing carbon emissions, thanks to the efficient way that the technology simultaneously derives power and heat from the combustion process'. However, as Mark Atkinson, the company's operations manager, explains, it is only through specifying and designing the plant accurately that the correct load, and therefore the desired savings, can be realized. PMID- 26281427 TI - Design and technology combine to good effect. AB - As flooring specialist, Gerflor, marks over 60 years supplying the healthcare sector, Virginia Harris, the company's Scottish sales and specification executive, takes a look at some of the recent trends in healthcare flooring, where attractive aesthetics, sustainability, a hard-wearing and robust construction, and cleaning and infection control considerations, are among the key criteria on specifiers' lists. She also considers the crossover between design and new product development. PMID- 26281429 TI - Flexible materials can adapt throughout life. PMID- 26281428 TI - Tough by name, tough by nature. AB - Few beds, one would imagine, could withstand three-quarters of a ton landing on them, but this was the challenge successfully met by a box bed from a furniture manufacturer for challenging behaviour environments, Tough Furniture, when, to reassure a customer that the bed could accommodate 30-stone patients, 13 of the company's staff jumped repeatedly on it to ensure that it would survive intact in a real-world setting. Such testing may seem extreme, but is vital, since much of the company's furniture is destined for environments where patients will abuse, and indeed attempt to destroy, components. As MD David Vesty explained to HEJ editor, Jonathan Baillie, when he visited the company's Shropshire headquarters, it is through manufacturing premium quality cabinet furniture that is both attractive and distinctly non-institutional, but will equally withstand the harshest use, that the company has ensured that its products can live up to the brand name. PMID- 26281430 TI - A 'compelling case' for bioliquids'. AB - Bioliquid is often overlooked by organisations when they look to reduce carbon emissions by moving heating or power generation away from fossil fuels to 'renewables'. According to Andrew Monaghan, commercial director at a specialist bioliquid producer, UK Renewable Fuels (UKRF), "although it doesn't have the glamour of some of the 'new' technologies, and bioliquids suffer something of a bad press from the environmental lobby, by any rational and informed reasoning, it really should be first on the list". Here he outlines why, as he puts it, 'second generation bioliquids should be the renewable of choice for many applications, as either the primary or a supplementary source of energy'. PMID- 26281431 TI - Giving credit where credit is due: Our commitment to ethical publishing. PMID- 26281432 TI - The Possibilities for Activity Scale (PActS): Development, validity, and reliability. AB - BACKGROUND: Laliberte Rudman proposed the concept of occupational possibilities to represent what older adults feel they "should be" and "could be" doing. PURPOSE: This study aimed to develop and validate a measure of perceived occupational possibilities: the Possibilities for Activity Scale (PActS). METHOD: Two factors of the PActS, activity expectations and activity self-efficacy, were operationalized in a 14-item instrument. The instrument was then evaluated with a sample of older adults diagnosed with cancer (n = 179). FINDINGS: The PActS demonstrated promising internal consistency reliability (stratified coefficient alpha = .77) and construct-related (r = .58; p < .0001), structural (chi-square = 61.57; CFI = .97; RMSEA = .05; TLI = .96; NFL = .91) and known-groups validity. IMPLICATIONS: The PActS appears to be a useful measure of internalized occupational possibilities for participation in activity for older adults with cancer. This scale can enhance the measurement of participation in activity by evaluating the perceptions of occupational possibilities. PMID- 26281433 TI - The development of the Pediatric Motivation Scale for rehabilitation. AB - BACKGROUND: Clinicians recognize that client motivation is key to optimizing rehabilitation; however, they are limited in its assessment by a paucity of motivation measures. PURPOSE: This paper presents the preliminary psychometrics of the Pediatric Motivation Scale (PMOT) designed to measure motivation from a child's perspective. METHOD: Content validity of the PMOT was measured through expert feedback (n = 12), and field testing ocurred with 41 children, 21 in rehabilitation and 20 healthy. Pearson product-moment correlations were used to analyze subscale correlations, test-retest reliability, and convergent validity with the Pediatric Volitional Questionnaire (PVQ). Internal consistency was measured using Cronbach's alpha. FINDINGS: Preliminary psychometric evaluation indicates strong internal consistency for PMOT total (alpha = .96) and subscales (alpha = .79-.91). The PMOT and PVQ moderately correlated in the rehabilitation subsample (r = .71, p < .01); no correlation was found in the healthy subsample (p > .05). Test-retest reliability was excellent (r = .97). IMPLICATIONS: This study provides preliminary psychometric evidence of the PMOT for children undergoing rehabilitation. These pilot findings warrant ongoing scale development. PMID- 26281434 TI - An international systematic mapping review of fieldwork education in occupational therapy. AB - BACKGROUND: Owing to its importance in preparing occupational therapists, fieldwork education has generated numerous studies. These have not been collected and reviewed, leaving researchers without a map for growing a science of fieldwork education. PURPOSE: This study aimed to systematically categorize the topics, research designs, methods, levels of impact, and themes that have and have not been addressed in fieldwork education scholarship. METHOD: Guided by a systematic mapping review design, 124 articles, identified through database searches and inclusion coding, were studied. Data were collected using a data extraction instrument and analyzed using Microsoft Access queries. FINDINGS: Papers primarily addressed curriculum (n = 51) and students (n = 32). Conceptual/descriptive inquiry methods (n = 57) were predominant. Qualitative (n = 48) and quantitative methods (n = 49) were used equally. Research outcomes mainly targeted perceived participation in fieldwork. Recurring themes included student perceptions, external influences, and transition to practice. IMPLICATIONS: Three recommendations were identified: strengthen procedures for studying singular fieldwork experiences, broaden rationales for studying fieldwork, and translate educational concepts for occupational therapy. PMID- 26281435 TI - Developing occupational therapy students' practice habits via qualitative inquiry education. AB - BACKGROUND: Accreditation standards and practice competencies underscore the importance of research for occupational therapy practice, but they do not guide how occupational therapy education addresses research. Despite the prominence of qualitative research in the health professions, there exists a need to articulate how and why qualitative inquiry is taught in occupational therapy education. PURPOSE: We discuss how qualitative inquiry education can develop habits of reflection and reflexivity, criticality, and active engagement in preparation for occupational therapy practice. KEY ISSUES: We hold that our students' professional abilities to practice in a well-reasoned, ethical, and responsive manner are enhanced by experiences with qualitative inquiry and suggest that there is potential in linking qualitative inquiry experiences to professional habit formation in occupational therapy education. IMPLICATIONS: In addition to teaching research for its own sake, we suggest that educators can adopt a broader view of how qualitative inquiry functions within occupational therapy education. PMID- 26281436 TI - [Home safety and severe mental disorders: Developing an evaluation tool]. AB - BACKGROUND: Home safety evaluation is an important issue within the context of current perspectives on accommodation for people with a serious mental illness who favour a more independent way of life. PURPOSE: This paper describes the development and content validation of the Evaluation de la securite a domicile et de la gestion des risques (ESGR), an occupational therapy assessment tool for people with a serious mental illness. METHOD: The ESGR was developed from scientific knowledge and clinical experience. Assessing content validity was done in two phases and involved the consultation of 11 experts. FINDINGS: In its current form, the ESGR includes 67 items organized into three categories (environment, occupation, person). IMPLICATIONS: According to the experts consulted, there is a clinical interest in using the ESGR to support occupational therapists in the assessment of home safety for people with serious mental illness. The statements are clear and representative of the concept and the target audience. PMID- 26281437 TI - Alternative approaches for the control of gastrointestinal nematodes in sheep farming: a review. AB - Gastrointestinal nematodes (GIN) are a serious health problem and represent the most significant constraint in sheep grazing operations. Problems tend to be worse in organic sheep farming systems, as a consequence of a less restricted access of animals to outdoor environment with a higher exposure to infective larvae. In domestic animals, GIN are effectively controlled by an aggressive prophylactic administration of commercially available anthelmintics. As a consequence to a common overdose and misuse of readily available antiparasitic treatments, there is an inevitable development of populations of GIN resistant to all major classes of anthelmintics. Also, the control of GIN that is based entirely on the anthelmintic use, threatens sustainability of the sheep farming worldwide. The combination of the optimized use of anthelmintic drugs and alternative approaches seem to be a reasonable choice in sustainable parasitic control programs that offer a substantial reduction of anthelmintic treatments and conservation of anthelmintic efficacy. In that aspect, a "targeted selective treatment (TST)" directed towards animals clinically diagnosed with GIN, seems to be an effective approach to leave some parasite populations unexposed to anthelmintics (refugia) and to reduce development of anthelmintic resistance. Also, many current research efforts aim to find and validate sustainable non chemotherapeutic approaches to GIN control, including changes in grazing management, optimized nutrition, dietary supplementation, consumption of plants with anthelmintic properties, biological control by nematophagous fungi, copper oxide wire particles (COWP), and homeopathic treatments. This manuscript outlines (outlines) and discusses relevant alternative approaches for GIN control in modern sheep farming systems. PMID- 26281438 TI - [Detection of Coxiella burnetii in dairy cattle bulk tank milk and single tank milk samples by confirmatory testing]. AB - Q fever is a worldwide zoonotic disease caused by the pathogen Coxiella (C.) burnetii. A wide range of animal species is susceptible to this intracellular bacterium with great importance in ruminants. Human infections occur mainly by airborne transmission. C burnetii was detected in animal products such as raw milk, raw-milk cheese and butter prepared from raw milk as well as in the meat of infected animals. In cattle milk, the pathogen was detected up to 13 months after calving. The risk of human foodborne C. Burnetii infection is still considered to be low, but cannot be completely ruled out and remains under discussion. The aim of this study was to compare different laboratory diagnostic methods for C. burnetii in milk sample. The bulk tank and individual milk samples were sent and studied at the National Reference Laboratory for Q-fever in the context of confirmatory laboratory testing after clinical suspicion or retesting of previously antibody detection was in the analysis of 888 individual milk samples a match of 93.3% (Cohen-kappa). A total of 173 bulk milk samples and 2,807 individual milk samples from bovine herds for the presence of C. burnetii DNA and antibodies were tested against the pathogen. The pathogen was detected in 62.5% of the bulk milk samples and up to 60% in individual milk samples. The highest proportion of positive bulk milks was determined as 68.3% in 2012. In individual milk samples, the highest proportion of seropositive samples was 62.2%. PMID- 26281439 TI - Spontaneous bacterial and fungal infections in genetically engineered mice: Is Escherichia coli an emerging pathogen in laboratory mouse? AB - The impact of particular microbes on genetically engineered mice depends on the genotype and the environment. Infections resulting in clinical disease have an obvious impact on animal welfare and experimentation. In this study, we investigated the bacterial and fungal aetiology of spontaneous clinical disease of infectious origin among the genetically engineered mice from our institution in relation to their genotype. A total of 63 mice belonging to 33 different mice strains, from severe immunodeficient to wild-type, were found to display infections as the primary cause leading to their euthanasia. The necropsies revealed abscesses localized subcutaneously as well as in the kidney, preputial glands, seminal vesicles, in the uterus, umbilicus or in the lung. In addition, pneumonia, endometritis and septicaemia cases were recorded. Escherichia coli was involved in 21 of 44 (47.72%) of the lesions of bacterial origin, whereas [Pasteurella] pneumotropica was isolated from 19 of 44 (43.18%) cases. The infections with the two agents mentioned above included three cases of mixed infection with both pathogens. Staphylococcus aureus was considered responsible for five of 44 (11.36%) cases whereas Enterobacter cloacae was found to cause lesions in two of 44 (4.54%) mice. Overall, 16 of the 44 (36.36%) cases of bacterial aetiology affected genetically engineered mice without any explicit immunodeficiency or wild-type strains. The remaining 19 cases of interstitial pneumonia were caused by Pneumocystis murina. In conclusion, the susceptibility of genetically modified mice to opportunistic infections has to be regarded with precaution, regardless of the type of genetic modification performed. Beside the classical opportunists, such as [Pasteurella] pneumotropica and Staphylococcus aureus, Escherichia coli should as well be closely monitored to evaluate whether it represents an emerging pathogen in the laboratory mouse. PMID- 26281440 TI - [Severe purulent and necrotizing glossitis in a fallow deer (Dama dama) due to an infection with the involvement of Mannheimia granulomatis]. AB - Post mortem examination of a young fallow deer (Dama dama) revealed a severe purulent and necrotizing glossitis as well as a multifocal necrotizing and ulcerative rumenitis and typhlitis. The animal was cachectic. Mannheimia (M.) sp. was isolated from the tongue lesions and identified as M. granulomatis by MALDI TOF MS and 16S rRNA sequencing. Mycosis and BVDV infection were excluded. Few publications are dealing with similar macroscopic findings associated with the isolation of M. granulomatis in cattle and roe deer. Therefore, M. granulomatis should also be taken into consideration when such lesions occur in other ruminants. Based on our findings in case of gross pathological lesions of the tongue of ruminants a Mannheimia granulomatis-infection should be investigated as well as the possible role of Fusobacterium necrophorum, Actinobacillus lignieresii or Actinomyces bovis. PMID- 26281441 TI - Platelet function in dogs with bacterial infections and leishmaniasis. AB - The objective of this study was to examine the influence of bacterial infections or leishmaniasis on primary haemostasis in dogs. Capillary bleeding time, automatic platelet function analysis (PFA-100), turbidimetric platelet aggregation, impedance aggregometry, platelet count and, in addition, the haematocrit were investigated in 25 dogs with bacterial infections or leishmaniasis . Results of these diseased dogs were compared to the control group and additionally classified into two subgroups based on criteria of systemic inflammatory response syndrome (SIRS) (groups "SIRS" and "Non-SIRS"). Dogs with infections had a significantly prolonged closure time of the PFA-100 using both cartridges (e. g., collagen/ADP: 83 [55-301] vs. 65 [47-99 s; median [minimum maximum]; p < 0.0001), a significant decrease in maximal aggregation of the turbidimetric aggregometry (e. g., ADP-induced: 45.2 +/- 26.8 vs. 67.3 +/- 21.8%; mean +/- SD; P = 0.003), a significant increase of collagen-induced impedance aggregometry and a significant suppression of arachidonic acid-induced impedance aggregometry. An enhanced collagen-induced impedance aggregation was the only significant difference between subgroups "SIRS"and "Non-SIRS". In conclusion, although individual tests indicate enhanced platelet aggregation, most of the in vitro tests revealed a normal to moderately reduced functionality. The reduced aggregabiity may partly indicate preactivation of platelets. PMID- 26281442 TI - [Prevalence of antibodies against Tick-Borne Encephalitis virus in dogs from Saxony, Germany]. AB - Tick-borne encephalitis (TBE) is the most important tick-transmitted viral disease in Europe and is caused by the TBE virus (TBEV), a member of the Flaviviridae family. In Germany, the vast majority of human TBE cases occurs in the south in so-called risk areas. However, in areas with only sporadic TBE cases, the respective risk assessment is hard to achieve. We therefore intend to use the prevalence of antibodies against TBEV in dogs as an indicator to trace such TBE endemic areas. Between August 2012 and March 2014, a total of 331 blood sera were collected from dogs all over Saxony, which hadn't left the state for the past five years. For the detection of antibodies against TBE-virus a commercial ELISA was used. Ten sera with positive or borderline ELISA results were retested by serum neutralization test. All seven ELISA-positive serum samples could be verified to contain TBE-virus-specific antibodieswith SNT titres between 1:15 and more than 1:40. We therefore found 2.1% seroprevalence in our samples. We conclude, that dogs can very well be used as sentinels, especially in areas with only sporadic TBE cases, although larger sample sizes are desired. PMID- 26281443 TI - Comparison of the prevalence of Mycoplasma species in dogs with and without respiratory disease. AB - Aim of the study was to investigate the prevalence of Mycoplasma species in dogs with and without signs of respiratory disease. Bronchoalveolarlavage fluid (BALF) and pharyngeal swabs were collected from 29 dogs with respiratory diseases (RD) and 16 dogs without signs of RD that were euthanised because of other diseases. Samples were tested for Mycoplasma species by PCR and culture, and sequencing was performed in Mycoplasma species-positive BALF samples. Pharyngeal swabs were positive for Mycoplasma species by PCR in 91.7% of dogs with RD and 86.7% of dogs without signs of RD (p = 1.000); BALF samples were PCR-positive in 37.9% of dogs with RD and 18.8% of dogs without signs of RD (p = 0.194) Mycoplasmo culture of BALF was positive in 28.6% of dogs with RD and in 18.8% without signs of RD (p = 0.730). When culture and PCR were compared, there was no significant difference in the detection rate of Mycoplasma species (p = 0.658) Sequencing detected different Mycoplasma species. Out of these, however, Mycoplasma cynos was isolated from four dogs with RD. There is no significant difference in the prevalence of Mycoplasma species between dogs with RD and dogs without evidence of RD; however, Mycoplasma cynos seems to be associated with respiratory disease. PMID- 26281444 TI - The occurrence of Anaplasma phagocyto- philum in wild bison from the Bialowieza Primeval Forest in Eastern Poland. AB - The aim of the present study was to investigate the occurrence of Anaplasma spp. in a group of 120 wild bison (Bison bonasus) from the Bialowieza Primeval Forest in eastern Poland and to determine which species of Anaplasma could infect these animals based on a PCR of a part of the 16S rRNA gene followed by sequencing. The PCR technique showed the presence of 16S rRNA Anaplasma spp. genetic material in the blood of 22 from a total of 120 animals. DNA amplification by means of the primers EHR 521 and EHR 747 gave a product size of 252-bp. The sequences of the PCR products obtained showed 100% homology with each other and 100% homology with the Anaplasma phagocytophilum GU 183908 sequence from our earlier study, isolated from a horse with a clinical case of anaplasmosis. The similarity of the sequences with the sequences of the 16S rRNA gene isolated from various Anaplasma species deposited in the GeneBank, ranged between 95.8% and 98.8%. Based on the results of molecular analysis, bacterial DNA detected in the blood of 22 wild bison was identified as Anaplasma phagocytophilum. PMID- 26281445 TI - Ectoparasites of hedgehogs (Erinaceus concolor) from Turkey. AB - Hedgehogs are small, nocturnal, spiny-coated animals that have been growing in popularity as exotic pets. However, these animals are host to a wide variety of viruses, bacteria, fungi and parasites, some of which are of zoonotic character. Thus, because hedgehogs have a potential role to transmit zoonoses including arthropod-borne diseases, we examined them for their ectoparasites. The study was carried out on hedgehogs found dead mainly due to road casualties in the Bursa province of Turkey. The ectoparasites were collected by both insecticide spraying of the body and inspection on a white paper carefully. Totally three species of ticks (Rhipicephalus sanguineus, Hyalomma aegyptium, Haemophysalis parvo) and one flea species (Archeopsylla erinacei) were detected. The prevalence of mixed infestation with both ticks and fleas was 45.5%. Haemaphysalis parva was reported for the first time from hedgehogs (Erinaceus concolor) in Turkey. The occurrence of ectoparasites and their potential role as vectors of certain zoonotic diseases are briefly discussed. PMID- 26281446 TI - [Relationship and repeatability of body condition scoring and backfat thickness measurement in dairy cows by different investigators]. AB - The determination of the body condition of dairy cows is a helpful instrument to assess the energy situation of individual cows and herds. Two methods for determining the body condition are well established in bovine practice, body condition scoring (BCS) and measurement of backfat thickness (BFT). The objectives of this study were to evaluate the repeatability of BCS on a five point scale with 0.25-points increments and the measurement of BFT by ultrasound (5 MHz linear probe) as well as the repeatability of measuring BFT at both sides of the cows back. Five investigators with different experience with BCS and BFT assessed a total of 94 cows repeatedly, resulting in 1806 BCS-measurements and 1723 (left) and 1733 (right) BFT-values. Weighted kappa coefficient was used to evaluate the agreement of repeated measurements and correlations were calculated for linear associations. Within-observer agreement of BCS and BFT was good for both methods (K = 0.67 and 0.78, respectively). Agreement was moderate to substantial for BCS and BFT depending on the investigator. Within-observer agreement of BFT at the right and left body side was substantial (K = 0.75). There was a high correlation between repeated measurements of BCS and BFT (r = 0.93 and r(c) = 0.91, respectively), and between BFT measured at the left and right body side (r(c) = 0.90). The correlation between BCS and BFT was moderate (r = 0.67). Overall, both methods demonstrated good repeatability applied by different investigators. In summary, BCS and BFT measurements are practical tools to contribute beneficially to herd health management. PMID- 26281447 TI - Effectiveness of salicylic acid paste for treatment of digital dermatitis in dairy cows compared with tetracycline spray and hydrotherapy. AB - The effectiveness of salicylic acid paste (PASTE) was tested for topical treatment of 25 acute and 25 chronic digital dermatitis (DD) lesions. Control groups with the same number of acute and chronic DD lesions were treated with topical oxytetracycline spray (SPRAY) and by washing only with water (HYDRO) respectively. The therapeutic effects were evaluated using a pain score, the healing rate, the lesion size and other parameters. Pre-treatment and control examinations were carried out on day 0, 4, 14 and 21. In the PASTE group, 76.0% of acute DD lesions were pain free and 64.0% of acute DD lesions were healed on day 21 showing a normal skin surface (MO). Only 28.0% of acute DD lesions treated with SPRAY and 16.0% treated with HYDRO had healed on day 21. A significantly higher healing rate was revealed in acute lesions for the PASTE compared to the HYDRO group (p < 0.05) for all three re-checks, and for the PASTE group compared with the SPRAY group (p < 0.05) for day 4 and day 14. Healing rates of chronic DD lesions were higher in the PASTE group with 44.0% on day 14 and 36.0% on day 21, compared with 16.0% in the SPRAY and 32.0% in the HYDRO group on day 14, and 20.0% (SPRAY) and 28.0% (HYDRO) on day 21 respectively. The recurrence rate of lesions after they had healed during the study period was 14.5% in total. Digital dermatitis lesions treated with salicylic acid paste and a wrap showed significantly higher healing rates within the study period, odds ratios for healing of acute lesions with PASTE were 4.5 to 6.7 times higher than with SPRAY, and 9.3 to 36.4 higher compared with HYDRO. PMID- 26281448 TI - Elevated testosterone levels in a racing horse due to an XY testicular disorder of sexual development. AB - A female thoroughbred successful in horse racing was positively tested for high testosterone values. This horse neither showed stallion-like-behaviour nor signs of ambiguous external genitalia. The karyotype of this horse was 2n = 64,XY and the sex-determining region of Y (SRY) PCR was positive. Hair samples tested for naturally testosterone revealed values normal for stallions, and tests for eight synthetic testosterone esters remained negative. The phenotype, ultrasonographic examination, hormone status, cytogenetic evaluation and molecular diagnostics lead to the diagnosis of an XY testicular disorder of sexual development (DSD) due to a complete androgen insensitivity syndrome. To our knowledge this is the first report about a thoroughbred in racing sports with an XY testicular disorder of sexual development. To date, intersex racing horses have never been described in thoroughbreds or a regulation for intersexes in regard to horse races has been issued. PMID- 26281449 TI - Mercury concentrations in feathers of Common Swifts (Apus apus). AB - Mercury (Hg) has been well studied as a bioaccumulated contaminant in aquatic ecosystems worldwide. It has been found to have negative effects on carnivorous and piscivorous bird species with the highest Hg concentrations at the top of the food chain. The objective of this study was to increase our knowledge of mercury exposure in insectivorous birds, especially in a species of the family Apodidae. The Common Swift (Apus apus) that specialises on feeding on aerial plankton molts and winters as a long-distance migrant in Sub-Saharan Africa. In the breeding seasons 2011-2013 the concentrations of Hg in primary flight feathers (P8-P10) in juvenile (n = 35) and adult (n = 25) injured Common Swifts were examined in the area of Hannover, Lower Saxony, Germany using cold vapour atomic absorption spectrometry. As a first reference, it was possible to determine feather Hg levels in adult (Mean +/- SD: 0.53 mg/kg wet weight +/- 0.37; Xmin-Xmax: 0.04 1.45 mg/kg; n = 25) as well as in juvenile Swifts (Mean +/- SD: 0.11 mg/kg wet weight +/- 0.06; Xmin-Xmax: 0.04-0.25 mg/kg; n = 35). The significant differences between the ages (p <= 0.001) are probably caused by differences in the feather growth, in accumulation of mercury for a longer time in adults as well as particularly in differences between mercury pollution in breeding and wintering ground. The mercury levels detected in swifts in this study are all below the range found by other authors to cause behavioural changes or reduced reproduction (5 mg/kg). PMID- 26281450 TI - Dry Decontamination. A white-powder letter sparks a workplace hazmat scare. PMID- 26281452 TI - Specialty Vehicles Assist Disaster Response. Five considerations for effectively preparing for MCIs. PMID- 26281451 TI - The Boston Bombing Review: What Went right and Wrong? Report evaluates the response to the 2013 terrorist attack. PMID- 26281453 TI - Evidence-based EMS: Psychological First Aid During Disaster Response. What's the best we can do for those who are suffering mentally? PMID- 26281454 TI - How FirstNet Will broaden communications. The wireless broadband network will connect police, fire and EMS through mobile devices. PMID- 26281455 TI - SMART Triage, World Leader in MCI Response. PMID- 26281456 TI - Telehealth Project Helps Cut Transports in Houston. PMID- 26281457 TI - Treatment Options for Hypoglycemia: Should It Be Gluca-gone? PMID- 26281458 TI - The payers perspective on MIH-CP programs. How to make a case for funding your project. AB - Here are some key points to consider when engaging in conversations with potential payers for EMS-based MIH-CP programs. The realignment of fiscal incentives within the healthcare system has created an environment that encourages providers and payers to work together to right-size utilization. Providers and payers are often unaware of the true value EMS agencies can bring to their patients through proactive and innovative patient navigation services. You need to tell them--or, better yet, show them. You may need to do a small demonstration project with a handful of patients to prove you can make a difference. In order to understand the new environment, you need to become well versed in healthcare metrics, specifically as they relate to the partners to whom you'll be proposing. Be sure you know things like readmission rates and penalties, value-based purchasing penalties, HCAHPS scores, MSPB and other motivating factors you. can use to help build the business case for your audience. For many in EMS, crafting partnerships for. payment of services not related to ambulance transport is a new and scary thing. Hopefully the examples provided here from payers paying for MIH services have demonstrated that their perspective is not much different from ours. We are all trying to do the right things for our patients, improve their experience of care and reduce the cost of the healthcare system. PMID- 26281459 TI - Altruism. PMID- 26281460 TI - In memoriam Esther Richwine. PMID- 26281461 TI - Tools for Taking the Measure Of Cancer Drugs. PMID- 26281462 TI - The Supremes Have Spoken And ACA Keeps On Hangin' On. PMID- 26281463 TI - Necessity of Payment Reform May Mother Big Data Into Being . PMID- 26281464 TI - Hospitals running amok with markups, pointing to need for oversight, say researchers. PMID- 26281465 TI - Tuning in to Telemedicine. PMID- 26281466 TI - Cost, Outcomes Mixed for Tele-ICU. PMID- 26281467 TI - HSAs Surge, Leaving HRAs in a Niche. PMID- 26281468 TI - Cancer Immunotherapies--and Their Cost--Take Center Stage at ASCO's 2015 Annual Meeting. PMID- 26281469 TI - Breakthrough Plug-and-Play Device Offers More Flexible Bronchoscopies. PMID- 26281470 TI - Half of American adults may have chronic kidney disease in their future.... PMID- 26281471 TI - Health Care Efficiency: Measuring the Cost Associated With Quality. PMID- 26281472 TI - Payers may cloud pharma's sunny outlook. PMID- 26281473 TI - Occupation--One of the Main Causative Factors for Hypertension. PMID- 26281474 TI - Hypertension, Prehypertension and Normotension among Police Personnel in a District of West Bengal, India. AB - OBJECTIVES: We conducted the present study to assess the prevalence of hypertension, prehypertension, normotension and the associated factors along with awareness, treatment and control of hypertension among police personnel in Bankura, West Bengal, India. METHODS: We collected information on individual, lifestyle, service-related and anthropometric characteristics of 1817 police personnel. We also measured blood pressure (BP) and plasma glucose level of the participants. Individuals were classified as hypertensive (BP >= 140/ 90 mmHg), prehypertensive (BP 120-139/ 80-89 mmHg) and normotensive (BP < 120/ 80 mmHg) on the basis of BP and their prevalence were expressed in percentages. Relation of individual, lifestyle, service-related and anthropometric characteristics with hypertension and/or prehypertension was examined with binary logistic regression. RESULTS: Prevalence of hypertension, prehypertension and normotension are 41.9%, 42.9% and 15.2% respectively. Even one-quarter of below 40 years subjects have hypertension. Mean BP remains in the prehypertensive range. Prevalence of hypertension and mean BP increases with age. Cardiovascular risk factors show clustering in higher age and with hypertension. Older age group, male gender, abdominal obesity, diabetes and service length are positively associated with hypertension and/or prehypertension. Around 40% of hypertensive knew their status, three-quarter of aware subjects received treatment and only one-third of treated subjects have controlled BP (< 140/ 90 mmHg). CONCLUSION: High prevalence of hypertension and prehypertension, high mean BP, mean age above 40 years and clustering of other risk factors pose a greater risk of cardiovascular morbidity in the current study population. PMID- 26281475 TI - Combining Fasting Plasma Glucose with Gamma-glutamyl Transferase Improves the Sensitivity to Predict Incident Diabetes in Asian Indian Men with Impaired Glucose Tolerance. AB - OBJECTIVE: To study the associations of baseline gamma-glutamyltransferase (GGT) and alanine transaminase (ALT) with incident diabetes among Asian Indian men with impaired glucose tolerance (IGT). METHODS: In a 2 year prospective, randomised, controlled primary prevention study of diabetes, among 537 IGT men aged 35-55 years, 123 incident diabetes (DM) cases occurred. Anthropometric {body mass index (BMI), waist circumference (WC)}, and laboratory measurements (fasting, 30 min and 2 hr plasma glucose (2 hr PG), HbA1c and plasma insulin, lipid profile, ALT, GGT) were estimated at baseline (Clinical Trial Identification No: NCT00819455). Predictive associations of baseline GGT and ALT values during the study were assessed using appropriate statistical methods. RESULTS: Baseline GGT but not ALT was significantly higher in incident diabetes cases. Mean (95% CI) GGT decreased in subjects who reverted to normal glucose tolerance (NGT), whereas it increased in subjects who deteriorated to diabetes (NGT:-3.5 (-6.4 to -0.6); IGT:0.3 (-3.0 to 2.4); DM:8.3 (3.6 to 13.0) UL(-1); P < 0.0001). The risk of DM significantly increased with increasing baseline GGT after adjusting for confounders such as BMI, alcohol drinking, 2 hr PG and insulin resistance (2.02[1.35-3.02]; P = 0.001). Receiver operating characteristic curve showed that the model comprising of baseline fasting plasma glucose (FPG) and GGT (area-under-curve(AUC)[95% CI]: 0.668 [0.613-0.722]; P < 0.0001) was equally sensitive in identifying subjects with risk of diabetes as compared to 2 hr PG (AUC [95% CI]: 0.670 [0.614-0.725]; P < 0.0001) and HbA1c (AUC [95% CI]: 0.677 [0.619-0.734]; P < 0.0001) alone. CONCLUSIONS: GGT was an independent predictor of incident diabetes. Combination of GGT and FPG offers a simple and sensitive tool to identify subjects at high risk of developing diabetes. PMID- 26281476 TI - Hypertension as a Risk Factor for Haemorrhagic Stroke in Females. AB - AIM: To study the effect of hypertension as a risk factor for haemorrhagic stroke in women compared to men. METHOD: Confirmed cases of haemorrhagic stroke by Computed Tomography scan were included in this study. The participants underwent detailed clinical examination based on preset questionnaire. Relevant laboratory investigations were done in this group. 100 consecutive cases were studied comparing the baseline characteristics with male patients admitted with haemorrhagic stroke. OBSERVATIONS: Among all the risk factors studied hypertension was the single most important risk factor causing intracerebral bleed. Forty seven point four percentage (47.4%) of females were hypertensive as against 61% in males. Blood pressure recording of females showed lower systolic and diastolic measurement compared to males and the difference was statistically significant with a p value of 0.000. Majority of the female patients were overweight with a significant difference in body mass index compared to males. (p value 0.006). CONCLUSION: Hypertension is an important risk factor for intracerebral bleed. Females developed intracerebral bleed at a lower blood pressure measurement compared to males. Females require better control of hypertension than males to prevent intracerebral bleed. PMID- 26281477 TI - Radiographic Abnormalities in the Feet of Diabetic Patients with Neuropathy and Foot Ulceration. AB - OBJECTIVE: People with diabetic neuropathy are frequently prone to several bone and joint abnormalities. Simple radiographic findings have been proven to be quite useful in the detection of such abnormalities, which might be helpful not only for early diagnosis but also in following the course of diabetes through stages of reconstruction of the ulcerated foot.The present study was designed to identify the common foot abnormalities in south Indian diabetic subjects with and without neuropathy using radiographic imaging. METHODS: About 150 (M:F 94:56) subjects with type 2 diabetes were categorised into three groups: Group I (50 diabetic patients), Group II (50 patients with neuropathy), and Group III (50 diabetic patients with both neuropathy and foot ulceration). Demographic details, duration of diabetes and HbA1c values were recorded. Vibration perception threshold was measured for assessment of neuropathy. Bone and joint abnormalities in the feet and legs of the study subjects were identified using standardised dorsi-plantar and lateral weight-bearing radiographs. RESULTS: Radiographic findings of the study subjects revealed that those with both neuropathy and foot ulceration and a longer duration of diabetes had more number of bone and joint abnormalities. Subjects with neuropathy alone also showed presence of several abnormalities, including periosteal reaction, osteopenia, and Charcot changes. CONCLUSIONS: The present findings highlight the impact of neuropathy and duration of diabetes on the development of foot abnormalities in subjects with diabetes. Using radiographic imaging can help in early identification of abnormalities and better management of the diabetic foot. PMID- 26281479 TI - Magnetic Susceptibility Effect in Diagnosis of Isolated Cortical Venous Thrombosis. PMID- 26281478 TI - Frailty Syndrome: A Review. AB - Frailty is a condition associated with ageing, co-morbidity and disability. Frailty was an elusive concept earlier despite efforts at consensus. There is now a better understanding of the multisystem dysfunction and the instability involved and an apparent clarity on measures that could correct deficits and ameliorate symptoms. The syndrome of frailty describes older people at a higher risk for adverse health outcomes such as illnesses, hospitalisations, disability and mortality. Clinically, it is diagnosed on combination of specific symptoms such as weight loss, muscle weakness/fatigue, low physical activity and slow walking speed. It can be identified by a multi-domain assessment of function. Interventions aimed at causative factors may help prevent conversion of frailty into disability. Current management measures are related to promoting physical activity including resistance training, clinical nutrition modifications in protein/amino-acids intakes, and usage of pharmacologic agents-ACE inhibitors, hormones-GH /testosterone in carefully investigated and selected patients. Large healthcare interventions and pharmacological trials are in progress. PMID- 26281480 TI - Chronic Necrotising Aspergillosis Presenting as Secondary Spontaneous Pneumothorax in an Immunocompetent Patient. PMID- 26281481 TI - Laryngeal Lymphoma: Before and After Chemotherapy. PMID- 26281482 TI - A Case Report of Complete Heart Block in an Uncommon Disease Entity: Kearns Sayre Syndrome. AB - Complete heart block has a varied aetiology; commoner being ischaemia and senile degeneration of AV node. In this article we report a case of complete heart block (AV nodal) in patient of Kearns Sayre Syndrome who has incidently SA node disease also which is further rarer in this disorder. PMID- 26281483 TI - A Rare Association of Parachute Mitral Valve with Double Outlet Right Ventricle and Severe Pulmonary Hypertension in an Adult. AB - Congenital mitral stenosis (MS) is a rare congenital cardiac malformation and the obstruction to the flow across the mitral valve can be caused by supramitral ring, commissural fusion, short chordae, anomalous mitral arcade, anomalous position of the papillary muscles and the so-called'parachute mitral valve'. We describe here the case of a 47 year old male diagnosed to have a double outlet right ventricle (DORV), subaortic ventricular septal defect (VSD) with no pulmonary stenosis, severe pulmonary hypertension and congenital MS due to parachute mitral valve. PMID- 26281484 TI - Rare Ocular Manifestations of Systemic Lupus Erythematosus--Two Case Reports. AB - In systemic lupus erythematosus (SLE), ocular involvement is common (prevalence up to 30%) but extremely varied.The most common manifestation is keratoconjunctivitis sicca (in about 25%). Though posterior segment disease is not uncommon, choroidal involvement and optic neuropathy are rare. Visual loss from neuro-ophthalmic involvement is often due to lupus optic neuropathy. Less than five percent of patients only present with sole ocular involvement at diagnosis. We report two patients who presented with decreased visual acuity and rare posterior eye changes as presenting features of SLE in the absence of other clinical manifestations and later developed lupus nephritis. PMID- 26281485 TI - Hypopituitarism and AutoimmuneThyroiditis Following Snake Bite: An Unusual Clinical Scenario. AB - Snake venom can cause local tissue damage and lead to coagulopathy, shock, neurotoxicity and acute kidney injury. Hypopituitarism is a rare complication following snake bite. It has been described following Russell's viper bite from Burma and South India. Herein we describe a patient who presented with severe thyrotoxicosis and partial hypopituitarism following snake bite. PMID- 26281486 TI - Neurological Manifestations in a Patient of Kikuchi's Disease. AB - Kikuchi's disease is a rare condition that mainly presents in young females along with lymphadenitis. Involvement of the nervous system is rare. We report a young female who presented with fever, headache, vomiting, lymphadenopathy and neurological manifestations in the form of aseptic meningitis, ataxia and paraparesis. Since the disease can be mistaken clinically and histologically for SLE, lymphoma and tuberculosis it is important to differentiate it from these conditions. Also our case emphasizes the importance of recognising this disorder in diagnosing patients with meningitis. PMID- 26281487 TI - A Case of Emphysematous Pyelonephritis. AB - Emphysematous pyelonephritis is a rare but dangerous condition in patients with D.M. and urinary tract infection. We report a case of emphysematous pyelonephritis who presented to us with acute abdomen and sepsis. Her CT abdomen showed air in the collecting system of left kidney. She was managed with, I. V. fluids, antibiotics, insulin, and percutaneous nephrostomy. But she died on the 3rd day of hospitalisation due to Multiorgan failure with sepsis. PMID- 26281488 TI - Allopurinol Induced DRESS Syndrome. AB - A 45 years old female on allopurinol for 3 months presented with itching, rash, facial oedema and eosinophilia with hepatic and renal dysfunction. Skin biopsy revealed interface dermatitis, suggesting the diagnosis of DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) syndrome. PMID- 26281489 TI - Leptospiral Uveitis. AB - Leptospirosis is widely regarded as the most widespread zoonosis in the world. Systemic leptospirosis is a biphasic illness. Ocular involvement in leptospirosis has been reported to be extremely variable, ranging from 2% to 90%. Ocular involvement is seen both in the systemic bacteraemic phase as well as in the immunological phase. Leptospiral uveitis is a common entity in the tropical countries. However it remains underdiagnosed mainly because ocular manifestations are noted in the second phase of illness. The primary anatomical location of inflammation is either in the anterior segment or pan uveitis. We report the case of a 40 year old lady who had presented to us with leptospiral uveitis. PMID- 26281490 TI - Dr. Hulusi Behcet. PMID- 26281491 TI - Dr. Hans Eggenberger. PMID- 26281492 TI - Benjamin Franklin. PMID- 26281493 TI - Dyke-Davidoff-Masson Syndrome--Revisited. PMID- 26281494 TI - Reply from Author. PMID- 26281495 TI - Spontaneous Radial Artery Thrombosis Recanalised by Intravenous Streptokinase--An Unconventional Successful Approach. PMID- 26281496 TI - Acute Acalculus Cholecystitis in Dengue Fever. PMID- 26281497 TI - Reply from Author. PMID- 26281498 TI - HPLC: its continuing role in diabetes monitoring. PMID- 26281499 TI - Glycated hemoglobin in the diabetic patient. PMID- 26281500 TI - Laboratory testing and pathological identification of cancer. PMID- 26281501 TI - Rapid testing for HIV: the state of the art, and a look ahead. PMID- 26281502 TI - Essential upgrades: the ASCP lends a hand in sub-Saharan Africa. PMID- 26281504 TI - CLIA-waived molecular diagnostic tests are poised to transform clinical Microbiology. PMID- 26281503 TI - Combating antibiotic-resistant bacteria: the Microbiology lab answers the challenge. PMID- 26281505 TI - Next-generation rapid diagnostics for HAIs and MDROs. PMID- 26281506 TI - Remembering Rosalind Franklin. PMID- 26281507 TI - March 2015 issue [p.4] describing the contribution made by Rosalind Franklin. PMID- 26281508 TI - Annual salary survey. PMID- 26281509 TI - Interpretation of qPCR curve shapes. PMID- 26281511 TI - UDI: What does it mean for the clinical laboratory? PMID- 26281510 TI - UVC irradiation. Is it the future of infection prevention in the clinical laboratory? PMID- 26281513 TI - The Internet of Things and keeping samples safe. PMID- 26281512 TI - Automated temperature monitoring systems: things to consider. PMID- 26281514 TI - There's No Place Like Home. PMID- 26281515 TI - How do you get a posterior baby, or even a breech baby, to turn into a more favorable position? PMID- 26281516 TI - Marion's Message. Disseminated Intravascular Coagulation. PMID- 26281517 TI - Posterior Perspective. PMID- 26281518 TI - Posterior Arrest. PMID- 26281519 TI - My Experience with OP Babies. PMID- 26281520 TI - The Emotional Impact of the Posterior Position. PMID- 26281521 TI - The Making of a Midwife. Elimination as a Foundation of Health. PMID- 26281522 TI - Wise Nutrition for Pregnancy. PMID- 26281523 TI - Posterior Birth and Babies. PMID- 26281524 TI - Posterior Questions and Answers. PMID- 26281525 TI - Homebirth Cesarean. Changing the Prenatal Conversation. PMID- 26281526 TI - Primal Heath Research vs. the NIH. PMID- 26281527 TI - Daisy C.H.A.I.N. Offering Free Postpartum Services to Families in Lane County, Oregon. PMID- 26281528 TI - Global Birth Models. PMID- 26281529 TI - The Art of Breastmilk Project. PMID- 26281530 TI - Giving Birth. Learning to Let Go. PMID- 26281531 TI - Elizabeth Nihell: A Feisty English Midwife (1723-1776). PMID- 26281532 TI - History of Midwifery in Japan. PMID- 26281533 TI - Do You Use Pelvimetry? Why or Why Not? PMID- 26281536 TI - [Review of scientific preservation techniques for traditional Chinese medicine becoming mouldy during storage]. AB - All kinds of traditional Chinese medicines (TCMs) differed from each other with different chemical components and properties. Owing to poor conditions and technologies, and the lack of scientific preservation, most TCMs will easily become mouldy during the processes of growth, harvest, handling, translation and especially storage, which will not only influence the quality, safety and efficacy of TCMs, but also cause serious waste and economic losses, and even do great harm to human health. The process of storage is closely related to the qualities of TCMs with many interference factors. Therefore, scientific preservation of TCM during storage is crucial to prevent them from being mouldy. This review analyzed the important harm of mouldy TCMs, summarized the internal and external factors of resulting in TCMs to become mouldy. Based on the above discussion, together with the characteristics and limitations of current TCM preservation techniques, we prospect novel, scientific and reasonable preservation techniques, expecting to provide references for scientific preservation of TCMs to avoid becoming mouldy and guarantee their qualities. PMID- 26281537 TI - [Advances in studies on pharmacological action of main chemical constituent of Curcuma Zedoary in preventing in-stent restenosis]. AB - Traditional Chinese medicine Curcuma Zedoary ( E'Zhu) contains essential oil, curcuminoid and other effective constituents, with such pharmacological actions as anti-platelet aggregation, lowing blood lipid, anti-oxidation and anti inflammation. In recent years, studies have showed that certain extracts and chemical components of E'Zhu could mitigate myocardial cell mitochondria injury and protect vascular endothelium by enhancing heme oxygenase-1 activity, inhibit nuclear factor NF-kappaB, target genes interleukin-associated kinase-1 (IRAK-1), tumor necrosis factor receptor-6 (TRAF-6) and vascular cell adhesion molecule-1 (VCAM-1), reduce inflammatory infiltration, and inhibit growth factor-induced smooth muscle cells (SMCs) proliferation and migration by impacting oxidation of cellular phosphatases. Due to its different functions in vascular endothelial cells and smooth muscle cells, E'Zhu has been applied in drug-eluting stents, with a potential effect in preventing in-stent restenosis and thrombogenesis. In this paper, studies on pharmacological effects and mechanisms of extracts and main chemical constituents from E'Zhu in preventing vascular restenosis were summarized. PMID- 26281538 TI - [Application of zebrafish in drug screens for active ingredients]. AB - Zebrafish has unique advantages over other animal models in the aspect of drug screens for active ingredients and gains more and more attentions in drug research and development recently. Thus, this article reviews the recent advance of zebrafish-based drug screens in Chinese traditional medicine (TCM) effective part research, monomer drug screening, activity evaluation of natural products, discovery of new uses for old drugs, and toxicity assessment in early-phase drug discovery. PMID- 26281539 TI - [Advance in studies on food allergy mechanism based on gut barrier]. AB - Food allergies, as a type of adverse immune-mediated reactions to ingested food proteins, have become a serious public health issue that harms children and adults health, with increasing incidence year by year. However, without effective therapy for food allergies, doctors-have mostly advised to avoid allergens and provided symptomatic treatment. According to the findings of many studies, allergic diseases are correlated with intestinal barrier function injury, as evidenced by the significant increase in the intestinal permeability among patients with food allergies. In this paper, recent studies on correlations between food allergies and intestinal barrier functions, intestinal barrier function injury mechanisms of allergic foods and food allergy intervention strategies based on intestinal barrier functions were summarized to provide reference for laboratory researches and clinical treatment of food allergic diseases. PMID- 26281540 TI - [Advance on chemical compounds of Ainsliaea genus]. AB - Plants in Ainsliaea genus, belongs to Compositae family, are traditional Chinese medicine and widely used in folk. These plants contain various types of chemical components, and main components are sesquiterpene lactone and its glycosides. In addition, there are triterpenoids, flavonoids, steroids, phenolic acid, long chain fatty acid and volatile oils. Recently, much attention has been payed to varlous research of A. fragrans. This paper reviewed and summarized the chemical components to provide the theoretical basis for the use of Ainsliaea. PMID- 26281541 TI - [Advances in studies on bear bile powder]. AB - In this paper, a detailed analysis was made on relevant literatures about bear bile powder in terms of chemical component, pharmacological effect and clinical efficacy, indicating bear bile powder's significant pharmacological effects and clinical application in treating various diseases. Due to the complex composition, bear bile powder is relatively toxic. Therefore, efforts shall be made to study bear bile powder's pharmacological effects, clinical application, chemical composition and toxic side-effects, with the aim to provide a scientific basis for widespread reasonable clinical application of bear bile powder. PMID- 26281542 TI - [Cloning and prokaryotic expression analysis of squalene synthase 2 (SQS2) from Salvia miltiorrhiza f. alba]. AB - According to the designed specific primers of gene fragment based on the Salvia miltiorrhiza transcriptome data, a full-length cDNA sequence of SQS2 from S. miltiorrhiza f. alba was cloned by the method of reverse transcription polymerase chain reaction (RT-PCR). The SmSQS2 cDNA sequence was obtained, this sequence is named SmSQS2 and its GenBank registration number is KM244731. The full length of SmSQS2 cDNA was 1245 bp, encoding 414 amino acids including 5'UTR 115 bp and 3'UTR 237 bp. Sequence alignment and phylogenetic analysis demonstrated that SmSQS2 had relative close relationship to the SQS2 of S. miltiorrhiza. The induction of E. coli [pET28-SQS2] in different temperature, induction time, IPTG concentrations and density of inducing host bacterium (A600) were performed, Shaking the culture at 30 degrees C until the A600 is approximately 0.6 and add IPTG to final concentration of 0.2 mmol x L(-1), and then the optimal expression of SmSQS2 recombinant protein were accumulated after the induction time of 20 h. The research provided important base for the study of sterol and terpene biosynthesis of SQS2 in S. miltiorrhiza f. alba. PMID- 26281543 TI - [Interaction relationship between secondary metabolites in Glycyrrhiza uralensis at condition of short-term exogenous glycyrrhizic acid simulation]. AB - In order to study the interaction relationship between secondary metabolites in Glycyrrhiza uralensis, and find out which secondary metabolite is significantly related to the content of glycyrrhizic acid, artificial applying ammonium glycyrrhetate solution was used to establish a high glycyrrhizic acid environment. The change of the 4 secondary metabolites was analyzed within 72 h after glycyrrhizic acid stimulation, while correlation statistical soft was applied to analyze the correlation of glycyrrhizic acid and other compositions. It turned out that it is feasible to establish high glycyrrhizic acid environment by glycyrrhizic acid root soaking in the concentration of 1.0 mmol x L(-1). There was significant positive correlation between glycyrrhizic acid and liquorice glycosides in short-term glycyrrhizic acid stimulation environment. It is concluded that glycyrrhizic acid accumulation internal of G. uralensis could be effected by artificial exogenous glycyrrhizic acid stimulation in certain case, and its accumulation was significantly related to the content of liquorice glycosides. PMID- 26281544 TI - [Study on microscopic identification of Astragalus complanatus and A. adsurgens seeds]. AB - Astragalus adsurgens seed is one of the most common adulterants of Astragali Complanati Semen in the market, whose morphological characteristics are very similar with A. complanatus seeds (Astragali Complanati Semen). Many identification methods have been reported, such as morphological identification, fluorescence method, ultraviolet spectrophotometry, TLC, HPLC, protein electrophoresis and so on, but there's no much about microscopic identification. In the present study, the morphological characteristics and microscopic characteristics of these two seeds were investigated, which could provide scientific evidence for the identification and classification of Astragali Complanati Semen. Our results showed that these two seeds were slightly different in the color and the appearance, but significantly different in the microstructure of the seed coat and the hilum, and the distribution of fat droplets in the cotyledon cells. So these microscopic characteristics can be applied for the identification of Astragali Complanati Semen. PMID- 26281545 TI - [Establishment of prokaryotic expression and optimization ox expression conditions of Eleutherococcus senticosus P450 gene]. AB - According to the sequence of P450 cDNA of Eleutherococcus senticosus, specific primers were designed. Frokaryotic ex pression vector pET30a-P450 was constructed and the prokaryotic expression conditions were optimized. Results showed that the BL21 after being transformed with the recombinant expression vector accumulated the high amount of recombinant protein. SDS-PAGE analysis showed that the recombinant protein was about 53 kDa. The recombinant accumulated the highest amount of recombinant protein af ter IPTG (1 mmol x L(-1)) at 27-37 degrees C for 24 h. Consequently P450 gene of E. senticosus could be expressed successfully by prokaryotic expression vector pET30a-P450. Induction temperature, IPTG concentration, medium type and amount of induction time could all influence the expression of target protein, but the impact strength was different. PMID- 26281546 TI - [Comparative study on identification of Clematidis Radix et Rhizoma from different origins based on microstructure and NIRS method]. AB - Microscopic identification and NIRS methods were applied to identify Clematidis Radix et Rhizoma of two different origins. The results showed that both methods could identify the samples. NIRS could identify the two samples nondestructively, and provides a basis for establishment of a standard herbs radix clematidis NIRS fingerprint in the future. PMID- 26281547 TI - [Exploring effective components of laxative effect of Anemarrhenae Rhizoma based on Chinese herbal processing theory]. AB - Anemarrhena asphodeloides processed by salt and raw product was compared including both chemical composition and laxative function in order to find the possible active substance to cure constipation. Processed and raw Anemarrhenae laxative effect on experimental constipation models was observed as well as chemical composition using UPLC-MS technology and the total sugar content was determined by phenol sulfuric acid method. Processed Anemarrhenae water extract improved excrement more than raw which has significant difference compared with the blank group (P < 0.05). On the other hand, the total ion flow spectrum showed no significant difference in most substance, but the total sugar content was significantly higher than raw product. Anemarrhenae ancient be recognized benefitting for draining body water in traditional Chinese medicine which has been lost in modern books because it is manifested as excellent laxative effect not diuretic effect. Saccharides carbohydrate may have closely relationship with this magically effect. PMID- 26281548 TI - [Synthesis, identification of artificial antigen of catalpol and preliminary study of immunogenicity]. AB - The method of monoclonal antibody-based immunoassay has a great importance in the study of quality control of traditional Chinese medicine (TCM) and detection of trace components in vivo animals. Synthesis of small molecule artificial antigen is the prerequisite for the establishment of this method. In present study, catalpol-BSA was synthesized by sodium periodate oxidation method. Matrix assisted laser desorption ionization-time-of-flight mass spectrometry ( MALDI-TOF MS) and molecular exclusion chromatography showed that catalpol was successfully conjugated with BSA. The mice could specifically produce anti-catalpol antibodies with titer up to 1:8000. The artificial antigen of catalpol was successfully synthesized. PMID- 26281549 TI - [Optimization of extraction process of compound Clematidis Radix spray by support vector machine]. AB - L9 (3(4)) orthogonal experiment was used to design the extraction technology of compound Clematidis Radix spray. Weight coefficients of active ingredients and dry extract rate were solved by information entropy. Support vector machine (SVM) was established and the model parameters were optimized through the genetic algorithm. Grid search algorithm was used for optimization of extraction technology of Clematidis Radix spray. The optimal extraction technology was to extract Clematidis Radix spray in water with 6 times the weight of herbal medicine for 3 times, with 2 h once. Bias of value between real and predicted by SVM was 1.23%. SVM was compared with traditional intuitive analysis of orthogonal design. It indicates that the new method used to optimize the extraction parameters of compound Clematidis Radix spray is more accurate and reliable. PMID- 26281550 TI - [Analysis of triterpenoids in Ganoderma lucidum by microwave-assisted continuous extraction]. AB - For further improving the extraction efficiency of microwave extraction, a microwave-assisted contijuous extraction (MACE) device has been designed and utilized. By contrasting with the traditional methods, the characteristics and extraction efficiency of MACE has also been studied. The method was validated by the analysis of the triterpenoids in Ganoderma lucidum. The extraction conditions of MACE were: using 95% ethanol as solvent, microwave power 200 W and radiation time 14.5 min (5 cycles). The extraction results were subsequently compared with traditional heat reflux extraction ( HRE) , soxhlet extraction (SE), ultrasonic extraction ( UE) as well as the conventional microwave extraction (ME). For triterpenoids, the two methods based on the microwaves (ME and MACE) were in general capable of finishing the extraction in 10, 14.5 min, respectively, while other methods should consume 60 min and even more than 100 min. Additionally, ME can produce comparable extraction results as the classical HRE and higher extraction yield than both SE and UE, however, notably lower extraction yield than MASE. More importantly, the purity of the crud extract by MACE is far better than the other methods. MACE can effectively combine the advantages of microwave extraction and soxhlet extraction, thus enabling a more complete extraction of the analytes of TCMs in comparison with ME. And therefore makes the analytic result more accurate. It provides a novel, high efficient, rapid and reliable pretreatment technique for the analysis of TCMs, and it could potentially be extended to ingredient preparation or extracting techniques of TCMs. PMID- 26281551 TI - [Simultaneously preparation of grams of high purity tyrosol, crenulatin and salidroside from Rhodiola crenulata]. AB - Tyrosol, crenulatin and salidroside are the main active constituents of Rhodiola crenulata, with extensive pharmacological activities. In the study, grams of high purity tyrosol, crenulatin and salidroside were simultaneously separated from R. crenulata by the first time. Firstly, R. crenulata was extracted by 70% alcohol. Then, with the yields of three compounds as the index, the macroporous resin was optimized. At last, grams of high purity tyrosol, crenulatin and salidroside were isolated by D-101 macroporousresin, purified by column chromatography. Detected by HPLC, the purity of three compounds were higher than 98%. This method has the advantages of simple process and operation, less dosage of organic solvent, highly yield and reproducibility, suitable for the simultaneously preparation of tyrosol, crenulatin and salidroside. PMID- 26281552 TI - [Analysis of four flavonoids in Lysimachia clethroides using ionic liquid assisted extraction]. AB - In order to established a method for simultaneous determination of isoquercitrin, astragaline, quercetin and kaempferol in Lysimachia clethroides, the ionic liquid 1-hexyl-3-methylimidazolium hexafluorophosphate ([HMIM]PF6) methanol was used as the ultrasound-assisted extraction solvent combing with RP-HPLC. A Purospher star RP-C1 column was used with the mobile phase of aceto- nitrile, methanol and 0. 4% phosphate acid by gradient elution at the detection wavelength of 360 nm. The flow rate was 0.7 mL x min(-1), and the column temperature was the room temperature. Under the optimized conditions, the linear ranges were 2.54 x 10(-2) 2. 54, 2.50 x 10(-2)- 2.50, 1.54 x 10(-3)-0.154, 1.49 x 10(-3)-0.149 microg for isoquercitrin, astragaline, quercetin and kaempferol, respectively. The average recoveries of the four constituents were 101.1%, 98.90%, 101.0%, 101.6%, respectively. The method was green, simple, rapid and accurate, and provided a valid method for analysis of isoquercitrin, astragaline, quercetin and kaempferol in L. clethroides. PMID- 26281553 TI - [Simultaneous determination of beta-elemene, curcumol, germacrone and neocurdione in volatile oil of Curcuma phaeocaulis and vinegar products by GC-MS]. AB - This study aims to develop a method for determination of beta-elemene, curcumol, germacrone and neocurdione in the volatile oil of Curcuma phaeocaulis, and to provide the basis of the quality control method for the volatile oil of C. phaeocaulis and the related preparations. Based on GC-MS, the 4 main compounds were simultaneously determined, with the internal standard n-tridecane. The Agilent 19091S-433 column (0.25 microm x 250 microm x 30 m) was adopted at the temperature of 250 degrees C, the programmed temperature method (60 degrees C for 1 min, 5 degrees C x min x to 110 degrees C for 5 min, 1 degrees C x min(-1) to 140 degrees C, 5 degrees C x min(-1) to 160 degrees C, 10 degrees C x min(-1) to 240 degrees C) was used. Helium gas was used as the carrier gas at a constant flow rat of 1 mL x min(-1), with an injection volume of 1 RL. Mass spectra were taken at 70 eV; the ion-source temperature was 200 degrees C. The relation time and character acteristic ions for each target compound were determined by full scan mode and SIM, and m/z 85.1, 93.1, 121.1, 107.1 and 180.1 were the detection ions of n-tridecane, beta-elemene, curcumol, germacrone and neocurdione. As a result, beta-elemene, curcumol, germacrone and neocurdione were all detected with good separation. They were all in a good linear relationship within each concentration scope. The average recovery rates were in the range of 98.2%-101%. So, the method can be used to control the quality of the volatile of C. phaeocaulis Val. and the preparations related. PMID- 26281554 TI - [A new benzaldehyde from aerial part of Rehmannia glutinosa]. AB - A new benzaldehyde, 3-hydroxy-4-(4-(2-hydroxyethyl) phenoxy) henzaldehyde(1), together with six known compounds, including isovanillic acid(2), pyrocatechol(3), glutinosalactone A(4), chrysoeriol(5), apigenin(6) and luteolin(7) were isolated from aerial part of Rehmannia glutinosa. The compounds were isolated by macroporous resin, silica gel, Sephadex LH-20 and HPLC chromatographies. The chemical structures of 1-7 were elucidated on the basis of spectral analysis (MS, 1D NMR and 2D NMR). PMID- 26281555 TI - [Chemical constituents from culture of Streptomyces sp. CPCC 202950]. AB - Eleven compounds were isolated from the culture of Streptomyces sp. CPCC 202950 by a combination of various chromatographic techniques including column chromatography over macroporous resin HP-20, MCI, and reversed-phase HPLC. Their structures were identified as 1H-pyrrole-2-carboxamide(1),5'-deoxy-5' methylthioinosine(2), vanillamide(3), trans-3-methylthioacrylamide(4), 1,2,3,4 Tetraydro-1H-pyrido[3,4-b]indole-3-carboxylic acid(5), cyclo(L-pro-L-tyr) (6), N [2-(4-hydroxyphenyl)]ethylacetamide(7), benzamide (8), cyclo ('L-leucyl-trans-4 hydroxy-L-proline)(9), cyclo-(Phe-Gly) (10), and tryptophan (11). Among them, compounds 1 and 2 were new natural products. In the preliminary assays, none of the compounds exhibited obvious inhibition of HIV-1 protease activity (IC50 > 10 micromol x L(-1)). PMID- 26281556 TI - [Studies on chemical compounds of Chlorella sorokiniana]. AB - Chemical constituents of Chlorella sorokiniana were isolated and purified by repeated column chromatographies, over silicagel and Sephadex LH-20. Their structures were identified on the basis of physicochemical properties and spectroscopic data analysis. Five compounds were obtained from the petroleum ether extract of Chlorella sorokiniana, and their structures were identified as (22E, 24R)-5alpha, 3beta-epidioxiergosta-6, 22-dien-3beta-ol(1),(24S)-ergosta-7 en-3beta-ol(2), loliolide(3), stigmasta-7,22-dien-3beta,5alpha,6alpha-triol(4), and 3beta-hydroxy-5alpha,6alpha-epoxy-7-megastigmen-9-one(5). The main liposoluble fractions from Chlorella sorokiniana maiuly contain fatty acids, alkyl acids and olefine acids. Components 1-5 were isolated from the genus Chlorella for the first time. PMID- 26281557 TI - [Study on chemical constituents of Achillea alpina]. AB - Twelve compounds were isolated from the aerial parts of Achillea alpina by column chromatographies on silica gel, Sephadex LH-20, and semi-preparative HPLC. The structures were elucidated on the basis of spectral analysis. The compounds were identified as pellitorine(1), 8,9-dehydropellitorine(2), (E,E)-2,4-undecadien-8, 10-diynoic acid isobutylamide(3), (E,E)-2,4-tetradecadien-8,10-diynoic acid isobutylamide(4),sintenin(5), 4',5,7,8-tetramethoxyflavone(6), chrysoplenetin(7), formononetin(8), aurantiamide(9), asperglaucide(10), artemetin(11), and eupatorin(12). compounds 1-5 were isolated from this plant for the first time, and compounds 6-10 were isolated from the genus Achillea for the first time. PMID- 26281558 TI - [Fragmentation pathways of five furocoumarine using line ion trap with orbitrapmass spectrometry]. AB - OBJECTIVE: The multiple levels fragmentations of five furocoumarine (psoralen, xanthotoxin, bergapten, oxypeucedanin, and byakangelicol) in Angelica dahurica have been demonstrated using LTQ-Orbitrap mass spectrometry with high resolution and high mass accuracy to discover the possible,fragmentation regularity. METHOD: Duringcollsion-induced dissociation (CID), the MS(n) data of the five compoundswhich were gained in the positive ion mode at 35ev collision energy by direct injection syrings method were analyzed using Xcalibar 2.0 Software to infer the formula of these fragmentations. RESULT: The results indicated that the five compounds have similar fragmentation process with CO meutral lost at C5,C8 subsituents and furan ring, meanwhile the meutralloss of CO2 occurred easily at lactone group. CONCLUSION: This method is helpful in identifying the structures of other furocoumarinein Angelica dahuricaand their metabolites in vivo. PMID- 26281559 TI - [Simultaneous determination of benzophenones and xanthone in leaves of Aquilaria sinensis by RP-HPLC-UV]. AB - This study is to develop a sensitive method by using reversed-phase high performance liquid chromatography coupled with UV detector (HPLC-UV) to simultaneously determine four bioactive compounds, iriflophenone 3-C-beta-D glucoside, iriflophenone 3,5-C-beta-D-diglucoside, mangiferin, and iriflophenone 2-O-alpha-L-rhamnoside in the leaves of Aquilaria sinensis. An Agilent Zorbax SB C, column (4, 6 mm x 250 mm, 5 microm) was used, and the gradient elution was performed with mobile phase of 0.1% aqueous phosphoric acid and acetonitrile at a flow rate of 1 mL x min(-1). The detection wavelength was 280 nm, and the column temperature was 25 degrees C. The four marker compounds were well separated with good linearity (R2 > 0.9990), precision, stability and repeatabili y. The recovery rates were in the range of 98.80%-101.39%. For 15 branch of the leaves, the contents of iriflophenone 3-C-beta-D-gluoside, iriflophenone 3,5-C-beta-D diglucoside, mangiferin, and iriflophenone 2-O-alpha-L-rhamnoside were between 0.41-14.48, 0.72-3.85, 4.30-29.07, 0.24-5.06 mg, respectivley. This method is precise, accurate and reliable, which provides an efficient way for the quality control of the leaves of A. sinensis. This will promote the comprehensive usage of this plant. PMID- 26281560 TI - [Rapid identification of chemical composition in safflower with UHPLC-LTQ Orbitrap]. AB - The UHPLC-LTQ-Orbitrap high resolution mass spectrometer was used to explore the chemical compositions in safflower. The rapid separation of the compositions was conducted by the UHPLC, following by high resolution full scan and MS2 scan, under the positive and negative ion mode. The chemical formula of compositions were deduced by full scan data in less than 5, then the potential structures were confirmed by the MS2 data. Forty-nine compounds were detected, of which 26 was identified, and 5 compounds was validated by the standard substances. PMID- 26281561 TI - [Effect of sesamin on pulmonary vascular remodeling in rats with monocrotaline induced pulmonary hypertension]. AB - OBJECTIVE: To observe the effect of sesamin (Ses) on pulmonary vascular remodeling in rats with monocrotaline ( MCT)-induced pulmonary hypertension (PH). METHOD: Totally 48 male Sprague-Dawley (SD) rats were fed adaptively for one week and then divided into the normal control group, the MCT group, the MCT +Ses (50 mg x kg(-1)) group and the MCT + Ses (100 mg x kg(-1)) group, with 12 rats in each group. The PH rat model was induced through the subcutaneous injection with MCT(60 mg x kg(-1)). After the administration for four weeks, efforts were made to measure the right ventricular systolic pressure( RVSP) and mean pulmonary artery pressure (mPAP) through right jugular vein catheterization, and isolate right ventricle( RV) and left ventricle( LV) +septum (S) and measure their length to calculate RV/ ( LV + S) and ratio of RV to tibial length. Pathologic changes in arterioles were observed by HE staining. Masson's trichrome stain was used to demonstrate changes in collagen deposition of arterioles. The alpha-smooth muscle actin (alpha-SMA) expression in pulmonary arteries was measured by immunohistochemisty. The total antioxidative capacity (T-AOC) and malondialdehyde (MDA) content in pulmonary arteries were determined by the colorimetric method. The protein expressions of collagen I, NOX2 and NOX4 were analyzed by Real-time PCR and Western blot. RESULT: After the administration for 4 weeks, Ses could attenuate RVSP and mPAP induced by MCT, RV/ (LV + S) and ratio of RV to Tibial length, alpha-SMA and collagen I expressions and remodeling of pulmonary vessels and right ventricle. Meanwhile, Ses could obviously inhibit the expressions of NOX2, NOX4 and MDA content and increase T-AOC. CONCLUSION: Sesamin could ameliorate pulmonary vascular remodeling induced by monocrotaline in PH rats. Its mechanism may be related to expressions of NOX2 and NOX4 expression and reduction in oxidative stress injury. PMID- 26281562 TI - [Effect of Xianxiong decoction on acute lung injury mice induced by lipopolysaccharide]. AB - OBJECTIVE: To investigate the effect of Xianxiong decoction on the mice with acute lung injury induced by lipopolysaccharide. METHOD: Eighty female ICR mice were randomly divided into 8 groups: model group, Xianxiong decoction group, Daxianxiong decoction group, Xianxiong decoction group without Kansui Radix group, Xianxiong decoction group without Glycyrrhizae Radix et Rhizoma group, Glycyrrhizae Radix et Rhizoma and Kansui Radix group, normal group and control group. Animals of each group, except normal group, were undertaken intraperitoneal injection and intranasal inhalation of lipopolysaccharide (LPS) on day 1, 2, 3 to establish acute lung injury (ALI) model. 30 min after modeling, 0.2 mL corresponding drugs were administrated to each mice, dexam ethasone and normal saline were given to the mice of control group and normal group respectively. White blood cell in blood, neutrophil percentage of blood and bronchoalveolar lavage fluid (BALF) supernatant, the ratio of wet and dry lung tissue ( W/D), histopathological changes of lung tissue were estimated. Sixty ICR mice were randomly divided into normal, model, control, high, middle and low dose Xianxiong decoction groups and were modeled in the same way. ELISA was applied to detect the level of NF-kappaB, TNF-alpha and IL-6 in BALF, PCR for NF-kappaB and TNF-alpha mRNA in lung tissue, and Western blot for NF-kappaB and TNF-alpha. Half of 20 ICR mice were administrated with Xianxiong decoction of its maximum tolerant normal saline. RESULT: Compared with model group, the number of WBC in blood of Xianxiong decoction group mice decreased (P < 0.01), percentage of neutrophils in both blood and BALF decreased as well (P < 0.01, P < 0.05); it also significantly reduced the ratio of W/D (P < 0.01); and found the alveolar wall, the number of inflammatory cells infiltrating improved, compared with model group. Xianxiong decoction reduced the level of NF-kappaB, TNF-alpha and IL-6 in BALF (P < 0.01, P < 0.01, P < 0.05); its high and low dose groups only found TNF alpha level declined. Five mice died 24 h after administration of Xianxiong decoction which indicated its toxicity when other influential factors were considered. CONCLUSION: Xianxiong decoction is effective on the ALI mice induced by LPS, but it is of toxicity at 3 g x mL(-1). PMID- 26281563 TI - [Study on inhibitory effect of water extract of Polygonum multiflorum on CYP1A2 and CYP2E1 enzymatic activities and mRNA expressions in rat liver]. AB - Rats were continuously given different doses of water extract of Polygonum multiflorum (1, 10 g x kg(-1)) for 7 days to prepare liver microsomes. Cocktail in vitro incubation approach and Real-time quantitative PCR technology were used to observe the effect of water extract of P. multiflorum on CYP450 enzymatic activities and mRNA expressions in rat liver. Compared with the blank control group, both 1, 10 g x kg(-1) water extract of P. multiflorum treated groups showed significant inhibitions in CYP2E1 enzymatic activities and mRNA expressions (enzymatic activities of CYP2E1, P < 0.01; mRNA expression of CYP2E1, P < 0.05 in 1 g x kg(-1) group, P < 0.01 in 10 g x kg(-1) group). They revealed a significant increase in the enzymatic activity of CYP3A1 (P < 0.01), but without significant change in mRNA expressions. The 10 g x kg(-1) group showed a significant inhibition in CYP1A2 enzymatic activities and mRNA expressions in rat livers (P < 0.01). PMID- 26281564 TI - [Study on inhibitory effect of EGCG on Calcium oxalate nephrolithiasis in rats and its related mechanism]. AB - In the study, the inhibitory effect of epigallocatechin gallate (EGCG) on Calcium oxalate nephrolithiasis and its possible mechanism were investigated. The rat Calcium oxalate nephrolithiasis model was induced through the combined oral administration of ethylene glycol and ammonium chloride, which was intervened with EGCG. Rat blood samples were collected to detect blood creatinine (Cr), blood urea nitrogen (BUN) and blood calcium. Rat urine samples were collected to observe and compare 24-hour urine volume, oxalic acid (Ox) and calcium in urine. Renal samples were collected to prepare tissue slices and observe the pathological changes in Calcium oxalate nephrolithiasis. The expression of osteopontin (OPN) in renal tissues was evaluated by Real-time PCR and Western blot. According to the results, compared with normal rats, rats in the nephrolithiasis model showed significant increases in Cr, BUN, urine Calcium, urine Ox and renal OPN expression (P < 0.05), but obvious decrease in 24-hour urine volume (P < 0.05); Compared with rats with nephrolithiasis, those processed with EGCG revealed remarkable declines in Cr, BUN, urine Calcium and urine Ox (P < 0.05), with significant rise in 24-hour urine volume (P < 0.05) in a concentration-dependent manner. Additionally, compared with the control group, nephrolithiasis rats showed significant pathological changes in Calcium oxalate calculus. After ECCG treatment, the renal pathological changes and OPN expression attenuated significantly in a concentration-dependent manner. The results showed that EGCG inhibits the formation of calcium oxalate nephrolithiasis in rats and shows a notable protective effect on renal functions. PMID- 26281565 TI - [Bioassay for enrich-blood bioactivity of Agelicae Sinensis Radix]. AB - Danggui, Agelicae Sinensis Radix, is a widely used Chinese herb to enrich blood, but its quality cannot be effectively assessed by the known chemical markers such as ferulic acid, ligustilide, polysaccharides, etc. A new bioassay was therefore developed to quantify the Enrich-Blood Bioactivity (EBB) for the quality assessment of Danggui raw materials. Danggui sample was first extracted with ethanol and water, respectively. Then the ethanolic extract and water extract were mixed as a test sample to quantify the amount of EBB by mice experiment. The blood deficiency mode in mice was developed by intraperitoneal injecting cyclophospharmide and phenylhdrazine hydrochloride. The quantity of red blood cell was chosen as EBB marker. Cyclosporine A was chosen as a control substance. EBB in analytes was quantified by the amount reaction of parallel line analysis (3, 3') method. The results indicated that the reliability test for quantifying EBB was passed through and the measured value was valid. The analytes showed the significant EBB (P < 0.05). The correlation coefficient was 0.9984 (n=5) between the amount of cyclosporine A (0.035-0.56 g x kg(-1)) and the increased number of red blood cell. The relative standard deviation (RSY) on the amount of EBB was estimated to be 6.15% (n = 6) by six replicated tests, and the confidence limit rate was 26.68% (n = 6). Five Danggui samples, which were collected from different cultivation areas with various morphological characters, showed the variety of EBB in the range of 21.95-44.16 U x g(-1). It is concluded that the developed method is accurate to quantify the EBB of Danggui raw materials, and is therefore suitable to assess its quality. PMID- 26281566 TI - [Effect of Paridis Rhizoma total saponins on apoptosis of human gastric cancer cell MKN-45 and Fas/FasL signaling pathway]. AB - OBJECTIVE: The study aimed to test if Paridis Rhizoma total saponins (PRTS) could induce apoptosis of human gastric cancer cell MKN-45. METHOD: Based on the previous researches, PRTS was set by different concentrations to treat human gastric cancer cell for 12 h (5, 10, 20 mg x L(-1)). Fluorescent staining methods were adopted to observe apoptotic morphological changes of MKN-45. The apoptosis rates were analyzed by flow cytometry with Annexin V-FITC/PI staining. The enzymatic activities of caspase-3 and caspase-8 were measured by ELISA. The protein levels of Fas and FasL were detected by Western blotting. RESULT: Under a fluorescence microscope, MKN-45 treated by PRTS was seen typical apoptotic morphological features. PRTS significantly increased the rate of apoptosis. Compared with the control group, there exsited significant differences in apoptosis rate of PRTS concentration of 20 mg x L(-1) (P < 0.01); besides, the enzymatic activities of caspase-3 and caspase-8 were promoted obviously after the effect of PRTS on MKN-45 cells for 12 h (P < 0.01). The protein levels of Fas and FasL in the MKN-45 were upgraded significantly. CONCLUSION: PRTS can induce apoptosis of human gastric cancer cell MKN-45 , which is concerned with caspase-3 and caspase-8 and upgraded Fas and FasL. PMID- 26281567 TI - [Effect of Draconis Sanguis-containing serum on NGF, BDNF, CNTF, LNGFR, TrkA, GDNF, GAP-43 and NF-H expressions in Schwann cells]. AB - OBJECTIVE: To observe the effect of Draconis Sanguis-containing serum on the expressions of NGF, BDNF, CNTF, LNG-FR, TrkA, GDNF, GAP-43 and NF-H in Schwann cells, and investigate the possible mechanism of Draconis Sanguis to promote peripheral nerve regeneration. METHOD: SD rats were randomly divided into 2 groups: the Draconis Sanguis group (orally administered with Draconis Sanguis containing balm solution) and the blank group (equivoluminal balm) to prepare Draconis Sanguis-containing serum and blank control serum. Schwann cells were extracted from double sciatic nerves of three-day-old SD rats, divided into 2 groups: the Draconis Sanguis group and the blank control group, and respectively cultured with 10% Draconis Sanguis-containing serum or blank control serum. The mRNA expressions of NGF, BDNF, CNTF and other genes in Schwann cells were measured by RT-PCR analysis 48 hours later. RESULT: Most of the Schwann cells were bipolar spindle and arranged shoulder to shoulder or end to end under the microscope and identified to be positive with the immunocytochemical method. To compare with the blank group, mRNA expressions of NGF, LNGFR, GDNF and GAP-43 significantly increased (P < 0.01). Whereas that of BDNF decreased significantly (P < 0.05), and so did that of TrkA, CNTF (P < 0.01), with no remarkable difference in NF-H-mRNA. CONCLUSION: Traditional Chinese medicine Draconis Sanguis may show effect in nerve regeneration by up-regulating mRNA expressions of NGF, LNGFR, GDNF and GAP-43 and down-regulating mRNA expressions of TrkA, BDNF and CNTF. PMID- 26281568 TI - [Effects of Tongxinluo capsule on sciatic nerve apoptosis in spontaneous type II diabetic KK/Upj-Ay mice and mechanism research]. AB - To investigate the effects of Tongxinluo capsule on sciatic nerve apoptosis in spontaneous type II diabetic KK/Upj-Ay mice, in order to explore its mechanism for improving diabetic peripheral neuropathy (DPN). KK/Upj-Ay mice were selected as the DPN animal model and randomly divided into the model, Tongxinluo low, middle and high group (1, 2, 4 g x kg(-1)). C57BL/6 mice were selected as the control group. Mice were given intragastrically for 12 weeks. Paw withdrawal latency, motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) were detected. Apoptotic rate were detected by FCM. Bcl-2, Bax, Caspase-3 mRNA and protein expression in sciatic nerve were examined by Real-time PCR and Western blot. p38MAPK, p-p38MAPK expression were examined by Western blot. In this study,the authors found that Tongxinluo capsule could increase paw withdrawal latency, MNCV and SNCV. Apoptotic rate of sciatic, the expression of Bax and caspase-3 were lower, while Bcl-2 expression was higher in Tongxinluo group than those in model mice. The expression of p-p38MAPK significantly decreased in Tongxinluo group. The results showed that Tongxinluo capsule has protective effects on diabetic peripheral neuropathy of mice via inhibiting cell apoptosis and suppressing the expression of p-p38MAPK. PMID- 26281569 TI - [Effect of Psoraleae Fructus and Myristicae Semen in "Ershen pill" on serum metabonomics in spleen-kidney Yang deficiency diarrhea rats before and after processing]. AB - The metabonomics method was used to study the intervention effect of Psoraleae Fructus and Myristicae Semen in "Ershen pill" on the changes in serum endogenous metabolites in spleen-kidney Yang deficiency diarrhea rats before and after processing, screen out differentiated metabolites related to spleen-kidney Yang deficiency diarrhea and explore the metabolic patterns related to spleen-kidney Yang deficiency diarrhea and the processing synergy mechanism of Psoraleae Fructus and Myristicae Semen in "Ershen pill". Efforts were made to detect SOD and MDA of each group, test rat serum metabolic fingerprints in different stages by using GC-MS, analyze by PCA and PLS-DA methods and screen out potential biomarks through VIP and t test. The results revealed that "Ershen pill" could enhance the level of SOD and decrease the level of MDA and identified 10 differentiated metabolites related to spleen-kidney Yang deficiency diarrhea. Compared with the model group, all of metabolites recovered to varying levels after being intervened with "Ershen pill", with the best effect shown in the "Ershen pill" IV group (salt-processed Psoraleae Fructus + bran-roasted Myristicae Semen). It is speculated that that Psoraleae Fructus and Semen Myristicae in "Ershen pill" show a synergistic effect by inhibiting peroxide, improving aglucolipid, amino acids and energy metabolism, with multiple target sites. PMID- 26281571 TI - [Current application of placebo in Chinese clinical studies in past 30 years]. AB - To analyze and discuss placebo-related information in clinical research literatures in the past 30 years, including placebo's dosage form, ingredients, preparation process and quality control. Effort were made to research the CNKI. full-text database to preliminary find 700 placebo-related clinical research literature, screen out 301 eligible articles by hand, read the literatures to extract placebo-related information and make statistics and discussions. According to the results, Chinese randomized placebo-controlled clinical studies were characterized by diverse dosage forms of placebo with lack of reports for components, as evidenced by the only 17 literatures describing placebo's preparation or specific composition among the 301 literatures. Placebo-controlled clinical trials covered a wide range of disease spectra, but with a specific tropism of diseases in terms of system classification. Although placebo plays a key role in blinded clinical studies, researchers made less records of placebo, perhaps because they paid less attention to placebo or more attention to the research process or restricted by other objective conditions. Moreover, placebo production, quality control and quality evaluation also need to be further standardized. PMID- 26281570 TI - [Predictive analysis on Shenmai injection-induced adverse reactions with Logistic model and ROC curve]. AB - To study relevant risk factors of Shenmai injection induced adverse reactions by using Logistic model and ROC curve, and made the prediction for the occurrence of relevant adverse reactions/events. Case data of patients treated with Shenmai injection were collected by using the prospective, multi-center, large-sample, nested-case control method, in order to analyze the risk factors of Shenmai injection-induced adverse reactions/events, establish the logistic model and draw the receiver operating characteristic (ROC) curve for risk factors. During the study, 7632 patients (including 3 477 males and 4 155 females) were included, and eight of them suffered adverse reactions/events. Based on a multi-factor Logistic model analysis, the age (> or = 50 years) (OR = 5.061, 95% CI: 2.197-7.924; P = 0.001), the total number of medication days (OR = -1.020, 95% CI: -l.652 - 0.388; P = 0.002) and the single dose (OR = 0.245, 95% CI: 0.127-0.364; P = 0.000) were significant independent risk factors for Shenmai injection-induced adverse reactions/events. According to the results, ROC curves were drawn with age (> or = 50 years), the total number of days of inedication and single dose; The area under ROC curves the joint predictor (0.9753, 95% CI: 0.9443-1.000, P < 0.005) was larger than that of the other three single indexes, with a higher risk prediction value. The independent risk factors for Shenmai injection-induced adverse reactions/events included the age (> or = 50 years), the total number of days of medication and single dose. In clinical practice, the age (> or = 50 years), the total number of days of medication and the medication dose can be substituted in the joint predictor calculation formula (P = 1 / [1 + e(-(-21.58 + 5.061 x Xage - 1.020 x Xd + 0.245 x X(mL)] to predict the potential adverse reactions of patients and adjust the dosage regimen. PMID- 26281572 TI - [A randomized, placebo controlled study on Fangfeng Tongsheng granule in treatment of sub-acute eczema]. AB - The clinical study was conducted to further evaluation the effectiveness and safety of Fangfeng Tongsheng granule in the treatment of sub-acute eczema (superficial cold and interior heat syndrome, exterior and interior sthenic syndrome). In the block randomized, multi-centered study, totally 108 patients were enrolled and assigned to two groups: 72 patients in the test group and 36 patients in the placebo control group. Those in the test group took Fangfeng Tongsheng granule with the dose of 3 g, twice a day, while those in the control group were give simulated agent granules with the same dose. The therapeutic course lasted for 14 days. Their efficacies in TCM syndrome, dermal symptoms and adverse events were observed. According to the test results, except for the one exit case, all of the remaining 108 cases, including 71 in the test group, and 36 in the control group, completed the clinical trial. As for the efficacy of TCM syndrome, after the medication for 2 weeks, the cure rate was 33.81% (24/71) in the test group and 0% (0/36) in the control group (P < 0.01), with a statistical difference between the two groups. Regarding the TCM score, after the medication for 2 weeks, the test group decreased by (12.82 +/- 7.96), while the control group decreased by (3.67 +/- 4.12), indicating a statistical difference between the two groups. As for the efficacy of dermal symptoms, after the medication for 2 weeks, the cure rate was 25.35% (18/71) in the test group and 0% (0/36) in the control group, with a statistical difference between the two groups. Regarding the dermal symptom score, after the medication for 2 weeks., the test group decreased by (10.04 +/- 7.17), while the control group decreased by (2.33 +/- 3.57), indicating a statistical difference between the two groups. There was no significant adverse event caused by Fangfeng Tongsheng granule. In conclusion, Fangfeng Tongsheng granule was effective and safe in treating subcute eczema (superficial cold and interior heat syndrome, exterior and interior sthenic syndrome). PMID- 26281573 TI - [Analysis of varieties and standards of labiatae medicinal plants used in Tibetan medicine]. AB - In this paper, an analysis was made on the varieties and standards of labiatae medicinal plants used in Tibetan medicine. The results showed 71 species of labiatae plants in 21 genera (including varieties) recorded in relevant literatures, involving 44 varieties of medicinal materials. Specifically, seven species (9.9%) were intersected with traditional Chinese medicines (TCM), 19 varieties (43%) were recorded in Chinese medicinal material standards at all levels, and 27 species (38%) were source plants. In Tibetan medicine standards and literatures, there are great differences between Tibetan names and translated Chinese names and among varieties of source plants. Apart from a few of varieties intersected with traditional Chinese medicines had complete standards and regulations in Chinese Pharmacopoeia, most of species only had characters, microscopic, physical and chemical identifications in Standards Issued by Ministry of Health-Tibetan Medicine, Tibetan Medicine Standard and local standards. Therefore, the Tibetan medicinal material variety-source specification and quality standard system shall be promoted on the basis of literatures research, investigations for resources and current applications and modern pharmaceutical studies. PMID- 26281574 TI - [Progress in study of spectrum-effect relationship of traditional Chinese medicine and discussions]. AB - Spectrum-effect relationship of traditional Chinese medicine is a scientific method based on fingerprint of traditional Chinese medicine, which studied the correlations between fingerprint and activity. The method revealed the activity related peaks and clarified the active components. It provided directions and thoughts for the clarification of pharmacodynamic material basis and establishment of evaluation method to reflect the inherent quality of traditional Chinese medicine. In this text we would make a systematic review about the progress in the study of spectrum-effect relationship of traditional Chinese medicine after summarized the latest years of investigations from researchers at home and abroad, including the establishment of fingerprint, efficacy evaluation, and data processing. The key problems in each part were clarified and corresponding discussions were made, providing thoughts and advices for the following study of spectrum-effect relationship of traditional Chinese medicine. At last we made a expecting on the development trend of spectrum-effect relationship of traditional Chinese medicine. PMID- 26281575 TI - [Autotoxic effect of ginsenoside extrats on growth of American ginseng in different medium]. AB - Ginsenosides are the abundant secondary metabolites in American ginseng (Panax quinquefolium), it could be released into soil through root exudation and decomposition during plant growth. This study determined ginsenoside contents in American ginseng cultivated soil by HPLC. Three ginsenosides, Rb1, Rb2 and Rd, were detected in the rhizosphere soil of 3-4 years old American ginseng cultivated in Huairou District, Beijing, and their contents were 0.80-3.19 mg x kg(-1). Correspondingly, the contents of the three ginsenosides in soil solution were 4-16 mg x L(-1) at field water-holding capacity of 20%. According to the field soil test data, we designed the concentration of ginsenosides for bioassays (0.2-125 mg x L(-1) in solution or 0.2-125 mg x kg(-1) in soil). The results showed that radicle lengths of American ginseng were reduced by 6%-23% in solution containing 0.2-125 mg x L(-1) ginsenoside extract, and a significant difference was observed at concentration of 125 mg x L(-1) (P < 0.05). The shoot lengths of American ginseng were not significantly inhibited by 0.2-125 mg x L( 1) ginsenosides extractions. After 20 days of growth in nutrient solution amended with 25 mg x L(-1) ginsenosides extraction, plant height of 3-year-old American ginseng seedling was decreased by 28% compared to the control, and the biomass of aerial parts was also reduced by 50% (P < 0.05). However, the growth of newly grown fibrous root was not significantly inhibited. Comparatively, when American ginseng embryos were cultivated into sterile or non-sterile soil, neither radicle lengths nor shoot lengths were significantly affected by 0.2-125 mg x kg(-1) ginsenoside extracts. In conclusion, ginsenosides showed autotoxic effect on growth of American ginseng radicle and adult seedling, however, this effect was weakened in field soil. PMID- 26281576 TI - [RNA interference and its effect of CYP76AH1 in biosynthesis of tanshinone]. AB - Tanshinones, the main bioactive compounds of Salvia miltiorrhiza, are the diterpenoid pigments, multiple genes were proved to be involved in their biosynthesis in plants. CYP76AH1 is the initial P450 gene in the tanshinones biosynthetic pathway, its function has been validated by yeast expression and in vitroenzymatic reaction. In order to clarify the function of CYP76AH1 in vivo, in this study, we constructedthe RNA interference of CYP7AH1 in S. miltiorrhiza hairy root. The RNA interference vector with a hairpin structure was constructed using the Gateway technology, and then the interference fragment was integrated into the genome of S. miltiorrhiza mediated by Agrobacterium rhizogenes. Several highly CYP76AH1 interference S. miltiorrhiza hairy roots were obtained for further analysis. PMID- 26281577 TI - [Correlation analysis of nutrients and microorganisms in soils with polyphenols and total flavonoids of Houttuynia cordata]. AB - The relationship of nutrients and microorganisms in soils with polyphenols and total flavonoids of Houttuynia cordata were investigated by measuring nutrients, enzyme activity, pH, concentrations of microbe phospholipid fatty acids (PLFAs) in soils, and determining concentrations of polyphenols and total flavonoids of H. cordata. The research is aimed to understand characteristics of the planting soils and improve the quality of cultivated H. cordata. The soils at different sample sites varied greatly in nutrients, enzyme activity, pH, microbic PLFAs and polyphenols and all flavonoids. The content of total PLFAs in sample sites was following: bacteria > fungi > actinomyces > nematode. The content of bacteria PLFAs was 37.5%-65.0% at different sample sites. Activities of polyphenol oxidease, concentrations of available P and content of PLFAs of bacteria, actinomyces and total microorganisms in soils were significantly and positively related to the concentrations of polyphenols and total flavonoids of H. cordata, respectively (P < 0.05) . The Content of fungi PLFAs in soils was significantly and negatively related to concentrations of polyphenols and total flavonoids of H. cordata, respectively (P < 0.05). This study provides evidence that effectiveness of the soil nutrient, which may be improved due to transformation of soil microorganisms and enzymes to N and P in the soils, was beneficial to adaptation of H. cordata adapted to different soil conditions, and significantly affects metabolic accumulation of polyphenols and flavonoids of H. cordata. PMID- 26281578 TI - [Identification and analysis of Corydalis boweri, Meconopsis horridula and their close related species of the same genus by using ITS2 DNA barcode]. AB - The study is aimed to ensure the quality and safety of medicinal plants by using ITS2 DNA barcode technology to identify Corydalis boweri, Meconopsis horridula and their close related species. The DNA of 13 herb samples including C. boweri and M. horridula from Lhasa of Tibet was extracted, ITS PCR were amplified and sequenced. Both assembled and web downloaded 71 ITS2 sequences were removed of 5. 8S and 28S. Multiple sequence alignment was completed and the intraspecific and interspecific genetic distances were calculated by MEGA 5.0, while the neighbor joining phylogenetic trees were constructed. We also predicted the ITS2 secondary structure of C. boweri, M. horridula and their close related species. The results showed that ITS2 as DNA barcode was able to identify C. boweri, M. horridula as well as well as their close related species effectively. The established based on ITS2 barcode method provides the regular and safe detection technology for identification of C. boweri, M. horridula and their close related species, adulterants and counterfeits, in order to ensure their quality control, safe medication, reasonable development and utilization. PMID- 26281579 TI - [Identication of pearl powder and conch powder from different origins by differential scanning calorimetry]. AB - The paper is aimed to establish a methods for identication of pearl powder and conch powder from different origins. Hermetic aluminum pan was used to encapsulate samples. The optimal testing conditions were: heating rate 10 degrees C x min(-1), sample weight 3 mg and nitrogen gas flow rate 40 mL x min(-1). The enthalpy values of pearl powder and conch powder was obvious different. Identication of pearl powder and conch powder by DSC is a practical method for its accuracy, convenience and practificality. PMID- 26281580 TI - [Preparation and identification of artificial antigen for rhein]. AB - The Rhei Radix et Rhizoma was one of the most widely used traditional Chinese medicine for its special biological activities. The content of rhein, one of its major compounds, was an important standard for the quantity control of Rhei Radix et Rhizoma. The major method used for the detection of rhein was instrumental analysis like HPLC, but it was complex, time-consuming and cannot detect large samples at the same time. The enzyme-linked imunmosorbent assay (ELISA) was accurate, reliable, simple, low costs, and of a high-throughout. Recently, it was widely used for the determination of those small molecule compounds in some traditional Chinese medicinal plants. In this study, an artificial antigen were synthesized by the carbodiimide (CDI) method. Rhein-bovine (rhein-BSA) conju gate and rhein-ovalbumin (rhein-OVA) conjugate, were produced as the immunogen and coating antigen, respectively. The conjugate and the hapten number in the conjugate were determined by UV-Vis spectrophotometry (UV). The conjugation ratio of Rhein and BSA was about 4.0:1, rhein acid and OVA was 2.6 : 1, respectively. Rhein-BSA conjugate was used to immunize Bal b/c mice to produce antiserum. The antiserum titer of the Rhein were higher than 8000 detected by ELISA. The successfully synthesized conjugate antigen rhein-BSA implies its feasibility in the establishment of fast immunoassay for the rhein content determination. PMID- 26281581 TI - [Effect of strains and parts on amino acids of Dendrobium officinale]. AB - The aim of the paper is to reveals the variations of Dendrobium officinale amino acids in different strains and parts for breeding excellent varieties, and providing scientific basis for the expanding of medicinal or edible parts. The contents of 17 amino acids in 11 strains of D. officinale were determined by hydrochloric acid hydrolysis method. The total amino acids content of leaves was from 6.76 to 7.97 g per 100 g, and the stems was from 1.61 to 2.44 g per 100 g. As the content of amino acids in leaves was significantly higher than that of stems, and the composition was close to the ideal protein standard proposed by FAO/WHO. The leaves of D. officinale had the good prospect for the development of functional foods. The 9 x 66 strain which with high yield and polysaccharide content had the highest amino acids content both in stems and leaves, indicated crossbreeding could improve the quality of varieties. Compared the amino acids content of D. officinale in two main harvest periods, the harvest time has a significant impact on amino acids content of D. officinale. This study demonstrates that the harvesting time of D. officinale stems is suitable for leaves as well, which is the period before bolssom. PMID- 26281582 TI - [Study on change rule of 6 ester-type alkaloids in process of Heishunpian]. AB - To study the variation of six ester-type alkaloids and characteristic fingerprints in the process from Radix Aconite Lateralis to Heishunpian and lay a foundation for the study of the processing principle of Heishunpian, HPLC. analysis was performed on a Phenomenex Gemini C18 (4.6 mm x 250 mm, 5 microm) with acetonitrile and 40 mmol x L(-1) ammonium acetate (adjusted to pH 10 with concentrated ammonia water) as mobile phase. The detection wavelength was set at 235 nm. The flow rate was set at 0.8 mL x min(-1) and the injection volume was 10 20 microL. Six ester-type alkaloids were determined and characteristic fingerprints of the process were established. As the process continues, the contents of diester diterpene alkaloids were decreased step by step, while the contents varia tion of monoester diterpene alkaloids were not obvious. Each sample showed significant difference in characteristic fingerprints. With the exception of 6 known monoester diterpene alkaloids and diester diterpene alkaloids, 13 peaks were marked in the characteristic fingerprints, of which the total change rule of the other 7 unknown peaks were similar with 3 diester diterpene alkaloids. The established method is accurate, reliable and repeatable, and can provide reference for revealing change rule of index components and illuminating processing principle in the process of Heishunpian. PMID- 26281583 TI - [Fingerprint and spectrum-effect relationships on Tripterygium glycosides preparation]. AB - Tripterygium glycosides preparation which extracted from the traditional Chinese herb Tripterygium wilfordii (TWHY), was widely used to treat the autoimmune diseases. Previous works demonstrated that TWHF had potent anti-inflammatory and immunosuppressive properties. But the different quality and high incident rate of side effects of different manufactures inhibited its clinical application. Since TWHF had been generally known to play a therapeutical effect by synergism of multiple constituents, it was necessary to build the relationship between the HPLC fingerprint and bioactivity so as to ensure the quality safety and efficacy. The HPLC fingerprint showed that description and content of peaks from different manufactures were diverse. Only 11 common peaks were found. In this study, mice spleen cells stimulated by Con A were used to test the proliferation inhibition bioactivity of TWHF preparations, which were incubated with 30, 15, 7.5, 3.75, 1.88 and 0.94 mg x L(-1) TWHF preparations for 48 h. The results showed that mice spleen cells proliferation was inhibited by all TWHF preparations significantly compared with the control group, which suggested the TWHF preparations showed immune suppress activity. The TWHF preparations from 7 manufacture showed different IC50 value, which might belong to different contents which showed in the HPLC fingerprint. Moreover, a relationship between the HPLC fingerprint and the bioactivity were established to identify important constituents by grey relational analysis (GRA). The result showed that all the contents were relative with the IC50, especially No. 5 and 10 peaks, but No. 1 peak, which was proved to be triptolide, had few contribute to the inhibition of mice spleen cells proliferation. The study of relationship between the HPLC fingerprint and the IC50 by GRA could help to investigate mechanism of bioactive and provide an evidence for the quantification of multi-constituents. PMID- 26281584 TI - [Study on sustained release preparations of Epimedium component]. AB - The formulation for sustained release tablet of Epinedium component was selected and the evaluation equation of in vitro release was established. The liquidity of component was improved with the help of colloidal silica aided by spray drying, which would be the main drug in the sustained release tablets. Dissolution was selected as an evaluation index to investigate skeletal material type, fillers, impact porogen, lubricants and other materials on the quality of sustained release tablet. The sustained release tablets were prepared by dry compression. Formulation of sustained release preparations was main drug 35%, HPMC K(4M) 20% and HPMC K(15M) 10% as skeleton material, MCC 31% as filler, PEG6000 2% as porogen and magnesium stearate 2% as lubricant. The sustained release tablets released up to 80% in 8 h. The zero order equation, primary equation and Higuchi equation could simulate the release characteristics of sustained release tablets in vitro, the correlation coefficients r were larger than 0.96. The primary equation was most similar in vitro release characteristics and its correlation coefficient r was 0.9950. The preparation method is simple and the results of formulation selection are reliable. It can be used to guide the production of Epimedium component sustained release preparations. PMID- 26281585 TI - [Studies on structure characteristic of polysaccharide P1A from Dicliptera chinensis]. AB - The chemical structures of P1 A was identified by complete acid hydrolysis, partial acid hydrolysis, periodate oxidation-Smith degradation, methylation analysis, IR and NMR. The results showed that P1 A had a backbone consisting rhamnose, mannose, glucose and galactose. The side chain possessed arabinose and xylose. 1-->, 1-->6 and non-reducing terminal linkages existed in polysaccharide P1A, but there are doubling amount of 1-->2 and 1-->4 linkages. Oxidable linkage of P1 A accounted for 45%, and inoxidable linkage of P1A accounted for 55%. Mannose, glucose and galactose were mainly linked by 1-->2 linkage. Rhamnose, arabinose and xylose were mainly linked by 1-->2 and 1-->4 linkages. PlA contained beta-Glc(1,6)-,beta-Gal(1,3)-,beta-Man(1,4)-beta-Rha,-Glc(1,4)-, Glc(1) ,-Gal(1,4)- and Man(1)-. PMID- 26281586 TI - [Study on effect of pH on rectum permeability of active ingredients in Reduning suppositories in vitro]. AB - OBJECTIVE: To investigate the effect of different pH on rectum permeability of chlorogenic acid and geniposide. METHOD: Four kinds of Reduning suppositories of different pH were separated and put into the rectum to study the suppositories in vitro and the content of chlorogenic acid and geniposide samples was determined by HPLC to calculate the permeation in 24 hours. RESULT: With increase of pH within 2.5-7.4, the steady state flux of chlorogenic acid was increased, but the steady state flux of geniposidesamples was steady. CONCLUSION: Adjusted the pH can increase the rectum permeability of active ingredients in Reduning auppositories. PMID- 26281587 TI - [Isolation, purification and identification of polysaccharides from Gynura divaricata]. AB - The purpose of this study was to isolate and purify polysaccharide from Gynura divaricata and analyze its monosaccharide composition. A water-soluble crude polysaccharide was obtained by hot water extraction, ethanol precipitation and deproteinization after degreasing. The crude polysaccharide then purified with DEAE-Sepharose Fast Flow column chromatography and dialysis. The monosaccharide composition and structure were analyzed by HPLC, UV spectrophotometer and 1H-NMR. The results showed that the purity and molecular weight of GDPS-2 and GDPS-3 were 87.3%, 2.03 x 10(4) Da and 90.9%, 4.29 x 10(4) Da, respectively. The UV spectrophotometer and 1H-NMR data suggested that glycosidic bond of GDPS-2 and GDPS-3 were a type. Both GDPs-2 and GDPs-3 were homogeneous polysaccharides, and GDPs-2 was mainly composed of glucuronic acid and xylose at a molar ratio of 1.1:0.63. GDPs-3 was mainly composed of rhamnose, glucuronic acid, galactose, xylose and galacturonic acid at a molar ratio of 0.32:6.0:0.21:1.75:4.3. PMID- 26281588 TI - [Flavone C-glycosides from seeds of Ziziphus jujuba var. spinosa]. AB - Five flavone C-glycosides were isolated from the methanol extract of the degrease seeds of Ziziphus jujuba var. spinosa though various column chromatography methods including silica gel, MPLC, and HPLC. The structures were elucidated as 6"-feruloyl- 6'''-vanillylspinosin(1), 6",6'"-diferuloylspinosin(2), spinosin(3), swertisin(4) and isoswertisin(5) based on the NMR and MS spectral data. 1 is a new compound. PMID- 26281589 TI - [Studies on non-alkaloid constituents from Ochrosia elliptica]. AB - The chemical consituents from Ochrosia elliptica were separated and purified by column chromatographies on silica gel, Sephadex LH-20, ODS and RP-HPLC. The structures of the isolated compounds were identified on the basis of physicochemical properties and spectroscopic analysis, as well as comparisons with the data in the literature. 18 compounds were isolated and elucidated as (+) -pinoresinol(1), (+) -medioresinol (2), (+) -lariciresinol (3), (+) -5'-methoxy lariciresinol(4), (+) -isolariciresinol (5), syringaresinol(6), episyringaresinol (7), ciwujiatone (8), zhebeiresinol (9), 7-hydroxycoumarin (10), 7 methoxycoumarin (11), scopoletin(12), isofraxidin(13), caffeic acid ethyl ester (14), ferulic acid (15), p-hydroxybenzaldehyde (16), vanillin (17), and vanillic acid(18). All compounds were isolated from the genus Ochrosia for the first time. PMID- 26281590 TI - [Studies on sesquiterpenes from Solanum septemlobum]. AB - By means of preparative HPTLC and column chromatography over silica gel and Sephadex LH-20, ten sesquiterpenes were isolated and purified from the whole plants of Solanum septemlobum Bunge. Based on the physico-chemical properties and spectral data, their structures were elucidated and identified as: lyratol D(1), solajiangxin B(2), 1 ,2-dehydrocyperone(3), solanerianone A (4), dehydrocarissone(5), ligucyperonol(6), nardoeudesmol A(7), solajiangxin F(8), and lyratol B(9), solajiangxin D(10). For the first time, compounds 1-10 were isolated from Solanum septemlobum, and compounds 5-7 were obtained from the genus Solanum. PMID- 26281591 TI - [Chemical constituents of Sapium sebiferum leaves]. AB - Chemical constituents of ethyl acetate extract of Sapium sebiferum leaves were isolated and purified by various chromatographic methods, including column chromatographies over silica gel, macroporous adsorption resin, and Sephadex LH 20, as well as preparative TLC and semi preparative HPLC. As a results, 15 compounds were separated from Sapium sebiferum leaves and their structures were examined by spectral analysis including NMR and MS data and identified as( + ) (7R,7'R,7"S,7'"S,8S,8'S,8"S,8'"S)-4", 4"'-dihydroxy-3,3',3",3',5,5'-hexamethoxy 7,9';7',9-diepoxy-4,8";4',8'"-bisoxy-8,8'-dineo-lignan-7",7"',9",9"'-tetraol(1) ,1-(4'- hydroxy-3'-methoxyphenyl)-2-[4"-(3-hydroxypropyl) -2", 6" dimethoxyphenoxy] propane-1, 3-diol (2), Thero-2, 3-bis-(4-hydroxy-3- methoxypheyl)-3-methoxy-propanol(3) , threo-5-hydroxy-3,7-dimethoxyphenyl propane 8,9-diol (4), boropinol B (5), threo-8S-7-methoxysyringylglycerol(6), 5 hydroxymethylfurfural(7), 5-( methoxy-methyl)-1H-pyrrole-2-carbaldehyde (8), quercetin (9) , kaempferol (10), ethyl gallate(11), coniferaldehyde(12), vanillin(13), 7-hydroxy-6-methoxy-2H-1-henzopyran-2-one(14),and 1-heptacosanol (15). All compounds except for compounds 9-11,14 were separated from this plant for the first time. PMID- 26281592 TI - [In vitro anti-inflammatory and free radical scavenging activities of flavans from Ilex centrochinensis]. AB - This study was carried out to evaluate the anti-inflammatory and free radical scavenging activities of flavans from flex centrochinensis S. Y. Hu in vitro and their structure-activity relationship. LPS-stimulated RAW 264.7 macrophage was used as inflammatory model. MTT assay for cell availability, Griess reaction for nitric oxide (NO) production, the content of TNF-alpha, IL-1beta, IL-6 and PGE, were detected with ELISA kits; DPPH, superoxide anion and hydroxyl free radicals scavenging activities were also investigated. According to the result, all flavans tested exhibited anti-inflammatory effect in different levels. Among them, compounds 1, 3, 4 and 6 showed potent anti-inflammatory effect through the inhibition of NO, TNF-alpha, IL-lp and IL-6, of which 1 was the most effective inhibitor, however, 2 and 5 were relatively weak or inactive. The order of free radical scavenging activities was similar to that of anti-inflammatory activities. Therefore, these results suggest that 3, 4 and 6, especially of 1, were,in part responsible for the anti-inflammatory and free radical scavenging activity of Ilex centrochinensis. Hydroxyl group at 4'-position of B-ring plays an important role in the anti-inflammatory and free radical scavenging capacities. PMID- 26281593 TI - [Quality assessment of Periplocae Cortex from different habitats by UPLC fingerprint and quantitative analysis]. AB - Ultra performance liquid chromatography (UPLC) was employed for simultaneous determination of three components and fingerprint analysis of Periplocae Cortex with gradient elution of mehtanol and water containing 0.1% phosphoric acid as mobile phase. Three components including chlorogenic acid, 4 methoxysalicylaldehyde and periplocoside were well separated under the analytical condition. Seventeen peaks were selected as the common peaks of 30 batches of Periplocae Cortex. The results showed that there is a significant difference in contents of periplocoside between the samples collected from Henan and Shanxi province. Based on the results of three components quantification and fingerprint analysis, hierarchical clustering analysis ( HCA) and principle component analysis (PCA) were used to further prove the differences between two group samples, and the results indicated that quality of Periplocae Cortex from Shanxi was more stable than that from Henan. The established UPLC fingerprint and quantitative analysis methods could be used efficiently in the quality control of Periplocae Cortex, and this study might contribute to the reasonable clinical application. PMID- 26281594 TI - [Research on inorganic elements of Asari Radix et Rhizoma from different localities and species]. AB - OBJECTIVE: To explore the character of inorganic elements in Asari Radix et Rhizoma (Xixin). METHOD: The contents of 53 inorganic elements in Xixin samples from different localities and species were determined by ICP-AES and ICP-MS. The statistical data were made using SAS. RESULT: The result demonstrated that Xixin has the high contents of Fe, Cr, Li. It has been observed that the content of Cu and Pb of the samples are much higher than the standard level. The results of hierarchical cluster analysis revealed two groups which correspond with the species of the samples. No correlations between the contents of the inorganic elements and the localities of the samples were found. Some characteristic elements were displayed in some specific areas. The difference of the contents of the 53 inorganic elements between root and rhizome of Xixin was reported for the first time. The primary form of inorganic elements in Xixin has been studied for the first time. The result demonstrated that the extraction rate between different elements varied, with the average extraction rate of (22.25 +/- 24.96)%. CONCLUSION: The inorganic elements analysis of Xixin can provide evidence of its identification, cultivation and application. PMID- 26281595 TI - [Determination of six C-Glycoside flavones and antitumor activity of water soluble total flavonoids from Isodon lophanthoides var. gerardianus]. AB - This research established an HPLC method for determination of six C-Glycoside flavones of warer-soluble total flavonoids from Isodon lophanthoides var. gerardianus (Benth.) H. Hara, and studied the antitumor activity of the warer soluble total flavonoids. The HPLC system consisted of Kromasil 100-5 C18 (4.6 mm x 250 mm, 5 microm) column and a solution system of methanol, acetonitrile and 0.5% formic acid gradient elution at a flow rate of 0. 8 mL x min(-1) and the wavelength of detector was at 334 nm. The column temperature was 25 degrees C. The antitumor activity of water-soluble flavonoids was assayed using HepG2 cell as the tested cell. The linear ranges of vicenin II, vicenin III, isoschaftoside, schaftoside, vitexin, 6, 8-di-C-a-L-arabinosylapigenin were 0.25-2.53, 0.12-1.20, 0.37-3.69, 0.16-1.63, 0.19-1.92, 0.14-1.42 microg, respectively. The average recoveries (n = 6) were 99.6% (RSD 0.87%), 100.2% (RSD 2.0%), 99.6% (RSD 1.8%), 97.9% (RSD 1.5%), 98.8% (RSD 1.2%), 98.6% (RSD 1.2%), respectively. After exposure in 24, 48, 72 h, the total flavonoids showed inhibitory effect on the proliferation of HepG2 cells with IC50 as the evaluation index, the IC50 values of 1.89, 1.71, 1.51 g x L(-1), respectively. The method is quick, simple and accurate with good re- producibility, and can be used for determination of vicenin II, vicenin III, isoschaftoside, schaftoside, vitexin, 6, 8-di-C-a-L arabino- sylapigenin in the warer-soluble total flavonoids from L lophanthoides var. gerardianus. The warer-soluble total flavonoids from L lophanthoides have inhibitory effect on the proliferation of HepG2 cells. PMID- 26281596 TI - [Regulatory effect of coptisine on key genes involved in cholesterol metabolism]. AB - To study the effect of cholesterol and 25-OH-cholesterol on cholesterol metabolism in HepG2 cells and the effect of coptisine (Cop) extracted from Coptidis Rhizoma (CR) in reducing and regulating cholesterol. In this study, TC, TG, LDL-c and HDL-c were measured by biochemical analysis; mRNA and protein expressions of LDLR, HMGCR and CYP7A1 were detected by qRT-PCR and Western blot. According to the results, cholesterol and 25-OH-cholesterol inducing could decrease in mRNA and protein expressions of LDLR and CYP7A1, so as to increase TC and LDL-c contents. However, Cop could up-regulate mRNA and protein expressions of LDLR and CYP7A1 and down-regulate that of HMGCR, so as to reduce TC and LDL-c levels. These findings suggested that Cop has potential pharmacological activity for reducing cholesterol, and may reduce cholesterol by regulating mRNA and protein expressions of key genes involved in cholesterol metabolism, such as LDLR, CYP7A1 and HMGCR. This study laid a firm theoretical foundation for developing new natural drugs with the cholesterol-lowering activity. PMID- 26281597 TI - [Protective effect of ginsenoside Rg1 again PC-12 cells in OGD injury through mTOR/Akt/FoxO3 signaling pathway]. AB - OBJECTIVE: To investigate the protective effect of ginsenoside Rg1 on oxygen glucose deprivation (OGD) in PC-12 cells, and preliminarily discuss the potential molecular mechanism of mTOR/Akt/FoxO3 signaling pathway. METHOD: The OGD PC-12 cell model was established. The cell viability was measured by MTT assay. After the pretreatment with Rg1 with the concentration of 10, 20, 40 micromol x L(-1) for 24 h, the cell viability was observed. Lactate dehydrogenase (LDH) release, superoxide dismutase (SOD) ac- tivity and malondialdehyde (MDA) level were detected by colorimetry assay. mTOR, p-Akt(ser473), p-Akt(tjr308), Akt, p-FoxO3, FoxO3 in cytoplasm and nucleus, and total FoxO3 protein expression were detected by Western blot assay. RESULT: OGD could significantly in- hibit cell proliferation in 4-24 h in a time-dependent manner. After pretreatment for 24 h, Rg1 (20, 40 micromol x L(-1)) could notably elevate the cell viability and SOD viability and reduce the LDH release and MDA content. Besides, Rg1 also inhibited OGD-induced mTOR and p-Akt(ser473) decreases. After treatment for 6 h, OGD could reduce FoxO3 phosphorylation and promote FoxO3 in cytoplasm. This data suggested that Rg1 could protect PC-12 cell injury through mTOR/p-Akt/FoxO3 signaling pathway. CONCLUSION: Ginsenoside Rg1 could attenuate OGD-induced PC-12 cell injury. Its action mechanism may be closely related to activation of mTOR/p Akt/FoxO3 signaling pathway. PMID- 26281598 TI - [Effect of improper diets on blood viscosity in SD rats in high-salt and fat diet and alcohol abuse simulation model]. AB - OBJECTIVE: To observe the effect of composite factors, like long-term high-salt & fat diet and alcohol abuse on blood viscosity and blood pressure in rats, and compare with a model induced by high molecular dextran, in order to build a chronic hyperviscosity aminal model which is similar to human hyperviscosity in clinic and lay a foundation for efficacy evaluation on traditional Chinese medicines. METHOD: Male SD rats were randomly divided into the normal group, the high molecular dextran (HMD) group and the high salt & fat and alcohol (HSFA) group. The HMD group was given normal diet and water for 23 day and then 10% HMD through tail vein for 5 days. The HSFA group was fed with high salt and high fat diets every day and alcohol for 20 h x d(-1) for 13 weeks. After the modeling, whole blood viscosity and plasma viscosity were measured in the 5th, 8th and 11th week. Blood pressure was measured in the 5d, 7h, and 10th week. Red cell count (RBC) and hematocrit (HCT) were measured in the 11th week. PAgT, Fb, ET-1, NO, PGI, TXA2 contents of the normal group and the HSFA group were measured in the 13th week, and IECa21 content was measured with flow cytometry. Result: After the modeling, the HMD group was in good conditions with glossy hairs and active behaviors. The HSFA group was depressed with withered hairs and less activities. During the 5th-11th weeks, the HMD group and the HSFA group showed higher values in high and low shear whole blood viscosity (WBV) than the normal control group. The plasma viscosity (PV) of HMD rats was significantly increased only in the 5th week, and that of HSFA rats significantly increased in the 8"' and 11th week, particularly in the 11'h week. In the 111h week, the HSFA group showed significant increases in RBC and HCT. After the modeling, the blood pressure of HMD rats showed no significant changes, but the blood pressure of HSFA rats significantly increased during 7' and 101h weeks, particularly in the 10"' week. In the 13th week, PAgT, IECa2+, Fb, ET-1 of HSFA rats significantly increased, but with decreases in NO and PGI2. CONCLUSION: Long-term high salt & fat and alcohol diets can cause abnormal blood viscosity in rats. WBV significantly increased since the 5th week in rats, and PV increased since the 8th week. The mechanism for increasing BV may be: (1) increases in RBC, HCT, and IECa2+, (2) PAgT increase, (3) Fb content increase, or (4) TXA2/PGI2, ET-1/NO imbalance. Although the modeling time with the method is longer than that with the HMD method, the model is more stable and moderate, and could lead to abnormal increases in WBV and PV; Whereas the HMD method only induced transient increase in plasma viscosity and abnormal increase in SBP. The model is more similar to traditional Chinese medicine syndromes and pathogenesis, with higher value for studies on efficacy of traditional Chinese medicines. PMID- 26281599 TI - [Anti-inflammatory mechanism research of flavonoid compounds in Dalbergiae Odoriferae Lignum by module-based network analysis]. AB - Dalbergiae Odoriferae Lignum as a traditional Chinese medicine (TCM) has been widely used for promoting blood circulation and removing blood stasis. Flavonoid compounds are main chemical constituents of Dalbergiae Odoriferae Lignum, which exert anti-inflammatory property. However, the underlying anti-inflammatory mechanisms of flavonoid compounds are incompletely understood. It has been reported that isoliquiritigenin, liquiritigenin, naringenin and butein possess anti-inflammatory property. The purpose of this study is to illuminate the anti inflammatory mechanism of flavonoid compounds based on the protein interaction network (PIN) analysis on molecular network level. 130 targets of the main medicinal ingredients of flavonoid compounds were gained though database retrieval. A protein interaction network of flavonoid compounds was constructed with 589 nodes and 216 interactions. By a graph theoretic clustering algorithm Molecular Complex Detection (MCODE), 26 modules were identified and analyzed by Gene ontology (GO) enrichment. Two modules were associated with anti-inflammatory actions. The most interesting finding of this study was that the anti inflammatory effect of flavonoid compounds may be partly attributable to inhibite FOS, PTGS2 expression, inhibite of IL-1beta release, and block the MAPK pathway and toll-like receptor pathway. PMID- 26281600 TI - [R-value comprehensive evaluation of effect of three methods for lung-kidney comprehensive evaluation study on R value of three methods for regulating and invigorating lung and kidney in regulating lung inflammation signaling pathways in COPD rats]. AB - Previous studies showed that three methods for regulating and invigorating lung and kidney (lung invigorating and spleen strengthening, lung invigorating and kidney tonifying, and Qi supplementing and kidney nourishing) could regulate inflammatory signaling pathways of chronic obstructive pulmonary disease (COPD) in rats, so as to alleviate inflammation. In the present study, R-value comprehensive evaluation method was used to evaluate the comprehensive effect of three methods for regulating and invigorating lung and kidney on inflammatory signaling pathways. Rats were randomly divided into control, model, lung invigorating and spleen strengthening, lung invigorating and kidney tonifying, Qi supplementing and kidney nourishing and aminophylline groups. The COPD rat models were established by cigarette smoking combined with bacterial infection, and orally administered with drugs between the 9th and 20th week. Afterwards, efforts were made to observe the long-term effects between the drug withdrawal and the 32rd week and detect indicators in two batches in the 20th week and 32th week. Specifically, (1) Linking JAK/STAT signaling pathway: JAK2 mRNA, and protein expressions of STAT-1, STAT-3, STAT-5, JAK-2; (2) NF-kappaB signaling pathway: Smad2 mRNA and protein expressions of I-kappaB, NF-kappaB, TGF-beta1; (3) PPARgamma and antioxidant signaling pathway: SOD, PGE mRNA, PPARgamma protein. According to the results, 5 indicators in JAK/STAT pathway, 4 indicators in NF kappaB pathway, and 3 indicators in PPARgamma pathway were significantly rectified by three methods for regulating and invigorating lung and kidney in between the 20th week and 32nd week. Between the 20th and 32nd week, the recipes for rectifying JAK/STAT pathway with intensity from high to low were recipes for lung invigorating and spleen strengthening, Qi supplementing and kidney nourishing, lung invigorating and kidney tonifying, aminophylline, particularly those for lung invigorating and spleen strengthening; The recipes for rectifying NF-kappaB pathway with intensity from high to low were recipes for lung invigorating and spleen strengthening, lung invigorating and kidney tonifying, Qi supplementing and kidney nourishing and aminophylline, particularly the first three types of drugs. The recipes for rectifying PPARgamma and antioxidant signaling pathway with intensity from high to low were recipes for lung invigorating and kidney tonifying, Qi supplementing and kidney nourishing, lung invigorating and spleen strengthening and aminophylline. Therefore, three methods for regulating and invigorating lung and kidney showed better long-term effects in regulating COPD lung inflammation signaling pathways. Specifically, recipe for lung invigorating and spleen strengthening showed a better effect in JAK/STAT and NF-kappaB pathways, while recipe for lung invigorating and kidney tonifying and Qi supplementing and kidney nourishing showed better effects in PPARgamma and antioxidant signaling pathways. In conclusion, R-value comprehensive evaluation method can evaluate the comprehensive effect of medicines and define the ranking of multiple drugs and their main targets. PMID- 26281601 TI - [Effects of compound Daqiqi decoction combined cisplatin on Bcl-2/Bax expression of nude mice ovarian cancer subcutaneous transplanted tumor]. AB - OBJECTIVE: To determine the compound Daqiqi decoction( CDQD) combined cisplatin plays on the cell apoptosis of subcutaneous transplanted ovarian cancer in nude mice, to provide theory evidence for clinical treatment. METHOD: Making the models of subcutaneous transplanted ovarian cancer in nude mice, and divide the 40 mice with tumor into 5 groups (n = 8), the model control group, CDQD low dosed group, CDQD high dosed group, cisplatin group, cisplatin combined CDQD group, killing all the mice after 3 weeks' treatment and stripping tumors. Measure the volume and weight of the tumor and calculate tumor growth curve damps, the inhibition rate. Examining the expression of the Bcl-2(B-cell leukemia /lymphoma 2) and Bax (Bcl-2 associated x protein) mRNA and protein by the RT-PCR and the Western blot. RESULT: (O)The tumor weight shows that there was certain lighter effect in each CDQD group, and compared with cisplatin groups has no statistical significance, the cisplatin combined CDQD group is obviously lighter than that of the other group(P <0.01). The tumor growth curve damps shows that compared with model control group, the treatment group tumors had some extent narrowing (P < 0.01). (2) RT-PCR results: Bax (Bcl-2 associated x protein) mRNA expression shows that compared with model control group, the treatment group has increased (P < 0.01), and the cisplatin combined CDQD group compared with the other group is the highest, there was significant difference with the rest of the treatment group (P < 0.01). In the Bcl-2 mRNA express lowest in cisplatin combined CDQD group (P < 0.01), there has no difference between CDQD high dose group and cisplatin group. (Western blot shows: compared with model control group, the Bax protein of treatment group has increased expression (P < 0.01), the expression of Bax protein in cisplatin combined CDQD group is the highest(P < 0.01). There has no difference between CDQD high dose group and cisplatin group. The Bcl-2 protein expression of the cisplatin combined CDQD group is the lowest (P < 0.01), there has no difference between CDQD high dose group and cisplatin group. CONCLUSION: The effect of CDQD on subcutaneous transplantation ovarian tumor has promoting apoptosis function, its mechanism may be related to downgrade the Bcl-2 expression, higher expression of bax, stimulation on the apoptosis of tumor cells; cisplatin combined CDQD have synergistic effect. PMID- 26281602 TI - [Intervention effect and mechanism of compound Ginkgo biloba preparations on nonalcoholic fatty liver]. AB - OBJECTIVE: To investigate the intervention effect and mechanism of compound Ginkgo biloba (CGB) preparations on nonalcoholic fatty liver disease (NAFLD). METHOD: The C57BL/6 mouse NAFLD model was induced with high fat diets. Since the 2nd week after modeling, the mice were orally administered with 600 and 200 mg x kg(-1) x d(-1) CGB for eight weeks. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), cholesterol (CHOL) and LPS in serum, as well as pathological changes and expression of tumor necrosis factor alpha (TNF-alpha) in hepatic tissues were observed. Changes in intestinal tight junction proteins ZO-1, Occludin, Claudin-1 in intestinal tissues were determined under microscopy. RESULT: Compared with the normal group, the model group showed obvious fatty degeneration in rat livers, with notable increase in TNF-alpha expression (P < 0.01), significant increases in ALT, AST, TG, CHOL and LPS in serum (P < 0.01, P < 0.05), injury in intestinal tight junction proteins, and remarkable declines in ZO-1, Occludin and Claudin-1 (P < 0.01). Compared with the model group, CGB high and low dose groups showed obvious relieves in fatty degeneration in rat livers and injury in intestinal tight junction proteins, significant reductions in TNF-alpha expression (P < 0.01, P < 0.05) and AST, TG, CHOL and LPS in serum (P < 0.01, P < 0.05) and remarkable increases in ZO-1 and Occludin expressions (P < 0.05). CONCLUSION: CGB can protect intestinal tight junction proteins, reduce intestinal leakage, relieve fatty degeneration and inflammations in livers and prevent NAFLD occurrence and development. PMID- 26281604 TI - [Study on compatibility of Salviae Miltiorrhizae Radix et Rhizoma and Chuanxiong Rhizoma based on pharmacokinetics of effective components salvianolic acid B and ferulic acid in rat plasma]. AB - A study was made on the pharmacokinetic regularity of effective components salvianolic acid B and ferulic acid in Salviae Miltiorrhizae Radix et Rhizoma (SMRR) and Chuanxiong Rhizoma(CR) in rats, so as to discuss the compatibility mechanism of Salviae Miltiorrhizae Radix et Rhizoma and Chuanxiong Rhizoma. Rats were randomly divided into three groups and intravenously injected with 50 mg x kg(-1) salvianolic acid B for the single SMRR extracts group, 0.5 mg x kg(-1) ferulic acid for the single CR extracts group and 50 mg x kg(-1) salvianolic acid B + 0.5 mg x kg(-1) ferulic acid for the SMRR and CR combination group. The blood samples were collected at different time points and purified by liquid-liquid extraction with ethyl acetate. With chloramphenicol as internal standard (IS), UPLC was adopted to determine concentrations of salvianolic acid B and ferulic acid. The pharmacokinetic parameters of salvianolic acid B and ferulic acid were calculated with WinNonlin 6.2 software and analyzed by SPSS 19.0 statistical software. The UPLC analysis method was adopted to determine salvianolic acid B and ferulic acid in rat plasma, including linear equation, stability, repeatability, precision and recovery. The established sample processing and analysis methods were stable and reliable, with significant differences in major pharmacokinetic parameters, e.g., area under the curve (AUC), mean residence time (MRT) and terminal half-life (t(1/2)). According to the experimental results, the combined application of SMRR and CR can significantly impact the pharmacokinetic process of their effective components in rats and promote the wide distribution, shorten the action time and prolong the in vivo action time of salvianolic acid B and increase the blood drug concentration and accelerate the clearance of ferulic acid in vivo. PMID- 26281603 TI - [Sodium houttuyfonate inhibits virulence related motility of Pseudomonas aeruginosa]. AB - Sodium houttuyfonate (SH) is a derivative of effective component of a Chinese material medica, Houttuynia cordata, which is applied in anti-infection of microorganism. But, the antimicrobial mechanisms of SH still remain unclear. Here, we firstly discovered that SH effectively inhibits the three types of virulence related motility of.Pseudomonas aeruginosa, i.e., swimming, twitching and swarming. The plate assay results showed that the inhibitory action of SH against swimming and twitching in 24 h and swarming in 48 h is dose-dependent; and bacteria nearly lost all of the motile activities under the concentration of 1 x minimum inhibitory concentration (MIC) (512 mg x L(-1) same as azithromycin positive group (1 x MIC, 16 mg x L(-1)). Furthermore, we found that the expression of structural gene flgB and pilG is down-regulated by SH, which implies that inhibitory mechanism of SH against motility of P. aeruginosa may be due to the inhibition of flagella and pili bioformation of P. aeruginosa by SR Therefore, our presented results firstly demonstrate that SH effectively inhibits the motility activities of P. aeruginosa, and suggest that SH could be a promising antipseudomonas agents in clinic. PMID- 26281605 TI - [Summary and analysis of safety warning on clinical application of anti-cold Chinese patent medicine preparations]. AB - In China, many surveys have shown that most people do not have a correct understanding about cold and administration of anti-cold Chinese patent medicine preparations. The author conducted a systematic summary and analysis on the actual application of anti-cold Chinese patent medicine preparations as well as the warning on safe application of anti-cold Chinese patent medicine preparations in Clinical Medication Information of China Pharmacopoeia, in the expectation of reducing the blind application of anti-cold Chinese patent medicine preparations and providing traditional Chinese medicine pharmacists new ideas in monitoring the safe application of exterior syndrome-relieving Chinese patent medicine preparations. PMID- 26281606 TI - [Study on professor Yan Zhenghua's medication regularity in treating heart diseases based on association rules and entropy cluster]. AB - In this study, Professor Yan Zhenghua's recipes for treating heart diseases were collected to determine the frequency and association rules among drugs by such data mining methods as apriori algorithm and complex system entropy cluster and summarize Pro- fessor Yan Zhenghua's medication experience in treating heart diseases. The results indicated that frequently used drugs included Salviae Miltiorrhizae Radix et Rhizoma, Parched Ziziphi Spinosae Semen, Polygoni Multiflori Caulis, Ostreae Concha, Poria; frequently used drug combinations included "Ostreae Concha, Draconis Os", "Polygoni Multiflori Caulis, Parched Ziziphi Spinosae Semen" , and "Salviae Miltiorrhizae Radix et Rhizoma, Parched Ziziphi Spinosae Semen". The drug combinations with the confidence of 1 included "Dalbergiae Odoriferae Lignum-->Salviae Miltiorrhizae Radix et Rhizoma", "Allii Macrostemonis Bulbus-->Parched Ziziphi Spinosae Semen", "Draconis Os-->Ostreae Concha", and "Salviae Miltiorrhizac Radix et Rhizoma, Draconis Os-->Ostreae Concha". The core drug combinations included" Chrysanthemi Flos-Gastrodiae Rhizoma-Tribuli Fructus", "Dipsaci Radix-Taxillus sutchuenensis-Achyranthis Bidentatae Radix", and "Margaritifera Concha-Polygoni Multiflori Caulis Platycladi Semen-Draconis Os". PMID- 26281607 TI - [Observation on clinical efficacy of Baoerkang san on spleen-deficiency and dampness-obstructing diarrhea in children]. AB - The study aims to observe the clinical efficacy of Baoerkang san on spleen deficiency and dampness-obstructing diarrhea in children. Children diarrhea divided into acute diarrhea (group I) and chronic persistent diarrhea (group II). A randomized, double-blind, positive control test was conducted for dose finding. The 340 cases with acute diarrhea in group I were divided into three groups: the high dose group (112 patients), the low dose group (113 patients) and the positive control group (115 patients), which were treated for 3 days. Their clinical efficacies were compared to evaluate the clinical safety of Baoerkang san. The 167 patients with chronic persistent diarrhea in group If were divided into the high dose group (56 patients), the low dose group (55 patients) and the control group (56 patients), which were treated for 5 days. Their clinical efficacy were compared to evaluate the clinical safety of Baoerkang san. According to the results, the cure rate and the effective rate of acute diarrhea and chronic persistent diarrhea in the high dose group and the low dose group were significantly higher than that of the positive control group (P <0. 05, P < 0.01). In the treatment of spleen-deficiency and dampness-obstructing diarrhea with traditional Chinese medicines, the cure rate and the effective rate of acute diarrhea and chronic persistent diarrhea in the high dose group and the low dose group were significantly higher than that of the positive control group (P < 0.05, P < 0.01). During the test, all of the three groups did not suffer any adverse event, with no any abnormality in general physical indexes. In conclusion, Baoerkang san shows a significant efficacy in treating acute diarrhea and chronic persistent diarrhea (spleen-deficiency and dampness-obstructing) and safe clinical application. PMID- 26281608 TI - [Mining analysis on composition and medication of menstruation prescriptions in Fu Qingzhu's Obstetrics and Gynecology]. AB - In this paper, menstruation prescriptions were selected from "Fu Qingzhu's Obstetrics and Gynecology" and analyzed by using GRI algorithm, correlation analysis, hierarchical clustering method through SPSS, Clementine and traditional Chinese medicine (TCM) inheritance auxiliary systems, in order to screen out 15 menopathy prescriptions, which involve 45 traditional Chinese medicine herbs. In the study, blood-tonifying and qi-tonifying herbs were found to be frequent in the prescriptions. The most frequent single herb was white paeony root, accounting for 9.6% in the total number of prescriptions; The most frequent herb pairs were white paeony root-radix rehmanniae preparata and paeony root-angelica sinensis. Among Fu Shan's menopathy prescriptions, 61 herbal pairs showed a correlation coefficient exceeding 0.05, which evolved into 16 pairs of core combinations. The analysis showed that menopathy prescriptions in volume 1 of "Fu Qingzhu's Obstetrics and Gynecology" focused on tonic traditional Chinese medicines involving liver, spleen and kidney and were adjusted according to changes in qi, blood, cold, hot and wet, which could provide a specific reference for further studies on Fu Shan's academic thoughts and traditional Chinese medicine clinical treatment of menopathy. PMID- 26281609 TI - [Study on composition, antibiotic activity and antioxidant activity of volatile oils from uyghur medicine Althaea rosea]. AB - Althaea rosea is a type of mallow plant. Its dry flowers are one of common herb in Uyghur medicines and recorded to have several efficacies such as external application for detumescence, moistening lung and arresting cough, sweating and relieving asthma, diminishing swelling and promoting eruption, soothing the nerves and strengthening heart. However, there are only fewer studies on effective components of A. rosea and no literature about its volatile oil and pharmacological activity. In this paper, the volatile oil of A. rosea was obtained by using the chemical distillation and extraction method. The individual chemical components were separated from the volatile oil and identified by the Gas Chromatograph-Mass Spectrometer technique (GC-MS). The antioxidant activity against free radicals was detected by the'ultraviolet and visible spectrophotometer method. The antibiotic activity was detected by the filter paper diffusion method. The experimental results showed nearly 70 compounds in the volatile oil, with complex chemical components. With a low content, most of the compounds were aromatic and aliphatic compounds and their derivatives. A. rosea had a better antibiotic activity for common microorganisms, with a wide antibacterial spectrum. According to the results, the volatile oil of A. rosea will have a good application value in medicine, food and cosmetic industries, which provided a scientific basis for the development of natural A. rosea resources. PMID- 26281610 TI - [Enlightenment of adverse reaction monitoring on safety evaluation of traditional Chinese medicines]. AB - The adverse reaction monitoring is important in warning the risks of traditional Chinese medicines at an early stage, finding potential quality problems and ensuring the safe clinical medication. In the study, efforts were made to investigate the risk signal mining techniques in line with the characteristics of traditional Chinese medicines, particularly the complexity in component, processing, compatibility, preparation and clinical medication, find early risk signals of traditional Chinese medicines and establish a traditional Chinese medicine safety evaluation system based on adverse reaction risk signals, in order to improve the target studies on traditional Chinese medicine safety, effective and timely control risks and solve the existing frequent safety issue in traditional Chinese medicines. PMID- 26281611 TI - [Study on meridian tropism of medicinal property theory for Chines medicines by supramolecular chemistry (I)]. AB - In this paper, based on the special influence of supramolecular chemistry on the basic theory of Chinese medicines ( CM) , the authors further analyzed the history of meridian tropism and natural origins of CM organisms and explained CM ingredients and the universal regularity of the automatic action of the supramolecular "imprinting templates" hole channel structure. After entering human bodies, CMs, as the aggregation of supramolecular "imprinting templates" , automatically seek supramolecular subjects that are matched with their "imprinting templates" in human meridians and organs for the purpose of self recognition, self-organization, self-assembly and self-replication, so as to generate specific efficacy in meridians and organs, which is reflected as the meridian tropism phenomena at macro level. This regularity can be studied by in vitro and in vivo experimental studies. In vitro methods are mostly supra molecular structure analysis and kinetic and thermodynamic parameter calculation; Whereas in vivo methods are dominated by the analysis on object component distribution, chromatopharmacodynamic parameters and network chromatopharmacodynamic parameters; Particularly, the acupoint-medicine method can simplify to study the supramolecular subject-object relations. Consequently, CM's'meridian tropism reveals the universal regularity for interactions of macromolecular and micromolecular "imprinting templates" of subjects and objects in natural organisms. As the first barrier for the material base of the CM theory and breakthrough in the modernization of the basic CM theory, meridian tropism plays an important role in studies on basic theories of the basic CM theory. PMID- 26281612 TI - [Study on incompatibility of traditional Chinese medicines]. AB - The incompatibility of traditional Chinese medicines is related to the clinical medication safety, so has attracted wide attentions from the public. With the deepening of studies on the incompatibility of traditional Chinese medicines represented by 18 incompatible herbs, the incompatibility of theory traditional Chinese medicines has raised to new heights. From the origin of incompatibility theory of traditional Chinese medicines, relationship of herbs, harms of incompatible herbs and principle of prevention to toxic effects of specific incompatible medicines, the innovation and development of the traditional Chinese medicine incompatibility theory was explored. Structurally, the incompatibility of traditional Chinese medicines refers to the opposition of two herbs based on seven emotions and clinical experience. The combination of incompatible herbs may lead to human harms, especially latent harm and inefficacy of intervention medicines. The avoidance of the combination of incompatible herbs and the consideration of both symptoms and drug efficacy are the basic method to prevent adverse reactions. The recent studies have revealed five characteristics of incompatible herbs. Toxicity potentiation, toxication, efficacy reduction and inefficacy are the four manifestations of the incompatible relations. The material changes can reflect the effects of toxicity potentiation and toxication of opposite herbs. The accumulation of toxicity and metabolic changes are the basis for latent harms. The antagonistic effect of main efficacies and the coexistence of positive and negative effects are the distinctive part of the incompatibility. The connotation of incompatible herbs plays an important role in the innovation of the traditional Chinese medicine incompatibility theory. PMID- 26281613 TI - Gritting (or should that be baring?) our teeth. PMID- 26281615 TI - Lengthy peer review times: What can be done? PMID- 26281614 TI - Will NOHP be toothless? PMID- 26281616 TI - Reply from the Honorary Editor. PMID- 26281617 TI - Quiz. External cervical root resorption. PMID- 26281618 TI - Every breath you take. PMID- 26281619 TI - Letter published in The Irish Times. PMID- 26281620 TI - You're in it together. PMID- 26281621 TI - Big Bad Ben. PMID- 26281622 TI - Management of an anxious child in the dental setting--a step-by-step approach. PMID- 26281623 TI - The occurrence of paraesthesia of the maxillary division of the trigeminal nerve after dental local anaesthetic use: a case report. AB - Paraesthesia can be a complication of surgical intervention. Its occurrence after dental local anaesthetic use is a rare event in general dental practice. Reported cases have mainly described its presentation for the mandibular division of the trigeminal nerve with very few reports for the maxillary division of this nerve. This report describes a case of paraesthesia in the maxillary region following local anaesthetic use prior to removal of an upper molar tooth. PMID- 26281624 TI - Adverse reactions to facial dermal fillers: a case report. AB - AIM: To describe an early-onset adverse reaction following the injection of facial fillers, and to summarise the current legislation and research regarding cosmetic dermal fillers. To emphasise that dermal fillers should be considered as part of a general dental practitioner's differential diagnosis for lower lip swelling. OBJECTIVES: (1) To describe the types of adverse reactions associated with dermal fillers in the literature; (2) to summarise the current European and Irish legislation and guidance regarding the use of these products; and, (3) to present a case study of an early-onset adverse reaction. CONCLUSION: Dentists should question patients regarding the use of cosmetic dermal fillers as part of the differential diagnosis of any intra-oral painless swelling where other pathology cannot be identified. PMID- 26281625 TI - Dentists' requirements for continuing professional development in Ireland. A pilot study conducted at University College Cork. AB - AIMS: To determine the self-assessed continuing professional development (CPD) needs of dental practitioners and identify how each discipline can best be served by a dental CPD programme. To set findings in the context of the available literature and contribute to the development of CPD programmes. METHOD: Topics were arranged into eight disciplines: practice management; paediatric dentistry; preventive dentistry; orthodontics; behaviour management; dentistry for people with a disability; oral medicine and surgery; and, restorative dentistry. A web based questionnaire was constructed and administered using a MarkClass 2.21 online survey tool. RESULTS: Fifty-six self-reported assessment responses were received, with three-quarters of participants having graduated within the past 10 years. Topics in oral medicine and surgery attracted consistently high levels of interest. A tendency to favour topics with a perceived direct clinical application was observed. Topics recommended by the Dental Council as core areas for CPD were given a high level of priority by respondents. CONCLUSIONS: Traditional lectures remain a valued mode of CPD participation. Practical courses were valued across all dental topics offered. A varied approach to determining the requirements of dentists is essential to appropriately support the practitioner. PMID- 26281626 TI - Reply: Spastic paraplegia in 'dominant optic atrophy plus' phenotype due to OPA1 mutation. PMID- 26281627 TI - [First delection of Borrelia burgdorferi sensu stricto genotype from Hyalomma asiaticum in Karamay, Xinjiang Uygur Autonomous Region of China]. PMID- 26281628 TI - Reply: Intravitreal injection of bevacizumab (Avastin) for treatment of stage 3 retinopathy of prematurity in zone I or posterior zone II. PMID- 26281629 TI - AMSN Lights the Way For Nursing Opportunities. PMID- 26281630 TI - Restating the Foci Of Nursing. PMID- 26281631 TI - Self-Efficacy Measurement and Enhancement Strategies for Medical-Surgical Clinical Nurses. AB - The Nursing Care Self-Efficacy Scale, a tool for measuring nurses' confidence in their nursing abilities, was developed and tested in a subset of medical-surgical clinical nurses. Scale construction, nurses 'self-efficacy, beliefs, and strategies for enhancing self-efficacy are described. PMID- 26281632 TI - Implementing a Comprehensive Functional Model of Care in Hospitalized Older Adults. AB - The implementation of a functional model of care in hospitalized older adults has had a positive impact on length of stay (LOS), 30-day re-admission rate, and fall rate. Estimated savings associated with the 3-month post-intervention LOS reduction was $200,000. PMID- 26281633 TI - Postoperative Ileus. AB - Postoperative ileus (POI) is a possible complication after abdominal surgery. The exact pathophysiology is unknown. Nurses should be aware of associated symptoms and evidence-based treatments to prevent or reduce the time of POI. PMID- 26281634 TI - Recognizing Signs of Prescription Drug Abuse and Addiction, Part I. AB - Prescription drug abuse/misuse is increasing. Nonmedical use of prescription medications, especially opioid analgesics, now is considered an epidemic in the United States. Medical-surgical nurses are in a strategic position to help address substance abuse problems in patients. PMID- 26281635 TI - Development of an In-House Review Course to Increase Med-Surg Certification. PMID- 26281636 TI - Acute Appendicitis: A Case Study Describing Standards of Care. PMID- 26281637 TI - Lasting Impressions: Using the Perspective of the Funeral Director to Guide Post Mortem Nursing Care Practice. PMID- 26281638 TI - Nurse Managers' Expectations and Utilization of Travel Nurses. PMID- 26281639 TI - Explaining Health Care and The Law to Patients. PMID- 26281640 TI - "Feed the Patient"--A Barrier Removed. PMID- 26281641 TI - Is Your Unit Up to Date With Quality Issues? PMID- 26281642 TI - 'That's What I Mean by a Hundred Little, a Thousand Little Deaths...': A Case Study of the Grief Experienced by the Mother of a Substance Abusing Child. AB - Parents of substance abusers experience stigma, regret, disrupted lives, loss of support, and loss of quality of life. Health professionals are in a unique position to locate or provide resources to support the family of the substance abusing individual. PMID- 26281643 TI - Improving Preceptors' Knowledge on Medication Error Reduction Strategies. AB - Preceptors are in an ideal position to change the paradigm for medication error reduction and detection. However, they must receive ongoing training and preparation for this role. An online learning module with specific focus on medication error reduction strategies could help preceptors meet the challenge of orienting novice nurses about safe medication administration. PMID- 26281644 TI - Implementation of Physician and Nurse Patient Rounding on a 42-Bed Medical Unit. AB - Physician-nurse collaborative relationships not only have an impact on the daily work environment, but also on positive patient outcomes. The purpose of this study was to evaluate physician and nurse perceptions of collaboration before and after implementation of collaborative patient rounding. PMID- 26281645 TI - Comparison of Robotic vs. Standard Surgical Procedure on Postoperative Nursing Care of Women Undergoing Total Abdominal Hysterectomy. AB - This exploratory study was conducted to determine if the postoperative course is different for women undergoing robotic-assisted total abdominal hysterectomy (TAH) compared to women undergoing traditional (open) TAH. This study adds to the evidence regarding potential benefits and complications of robotic-assisted gynecologic surgery, and identifies specific areas for further research. PMID- 26281646 TI - Understanding Case Studies. PMID- 26281647 TI - Management of Attention. PMID- 26281649 TI - [SURGEON IN THE PAST AND FUTURE]. PMID- 26281648 TI - Patient Engagement and Self-Management Across the Care Continuum. PMID- 26281650 TI - [MESSAGE FROM "CLINICAL STUDY PROMOTION COMMITTEE" OF JAPAN SURGICAL SOCIETY]. PMID- 26281651 TI - [PARADIGM SHIFT IN VARICOSE VEIN THERAPY AND ITS IMPACT ON SURGEONS]. PMID- 26281652 TI - [MANAGEMENT STANDARDS FOR QUALIFIED PHYSICIANS AND MEDICAL FACILITIES FOR ENDOVENOUS ABLATION OF VARICOSE VEINS]. AB - Endovenous ablation of saphenous veins using laser energy was approved by the Japanese Ministry of Health, Labor and Welfare in 2011 as a more effective, less invasive method than classical treatment for varicose veins. New medical laser and radiofrequency devices for this purpose were also approved in 2014. A requirement for the treatment of varicose veins with health insurance reimbursement using these devices is a physician with sufficient knowledge of endovenous ablation. The management standards for endovenous ablation set by varicose vein specialist medical societies are used to accredit qualified physicians who have basic clinical experience in the treatment of varicose veins, qualified instructors, and safe, effective medical facilities. PMID- 26281653 TI - [ADVANCES IN STRIPPING SURGERY FOR INCOMPETENT SAPHENOUS VEINS]. AB - A classic Babcock procedure that removes the whole length of incompetent great saphenous veins (GSV) is known to be associated with massive surgical stress. With the use of tumescent local anesthesia and stripping wire to remove the femoral segment of the GSV in an invagination technique, day surgery has become possible. PMID- 26281654 TI - [ENDOVENOUS LASER TREATMENT FOR VARICOSE VEINS]. AB - Varicose veins are a common condition attecting approximately 10 million patients in Japan. The main cause of varicose veins is reflux of the saphenous vein, and conventional treatment for several decades was stripping the affected saphenous vein and phlebectomy. Endovenous laser treatment (EVLT) is a less-invasive treatment method in which the saphenous vein is ablated with a laser under local anesthesia. EVLT has been approved by the Japanese Ministry of Health, Labor and Welfare since 2011, and we have performed EVLT on 5,160 legs with saphenous insufficiency with no severe complications including deep vein thrombosis except for one case of arteriovenous fistula. EVLT appears to be a safe, effective treatment option for varicose veins with saphenous insufficiency. PMID- 26281655 TI - [RADIOFREQUENCY ABLATION FOR THE TREATMENT OF VARICOSE VEINS]. AB - Significant advances in the endovenous technique for treating incompetent saphenous veins could change the surgical strategy in patients with varicose veins. Radiofrequency ablation (RFA) was approved as a new technique for the treatment of varicose veins in Japan in June 2014. In RFA, the ablation temperature is controlled by a sensor at the upper end of the catheter. The vein wall is heated with stable conductive power of 120 degrees C, resulting in endothelial denudation. The RFA method was approved in 1998 in Europe and in 1999 in the USA. The ClosurePLUS catheter was developed in 2003 and ClosureFAST in 2006. High occlusion rates and lower postoperative complication rates were reported with ClosureFAST than with ClosurePLUS. It is expected that this new ablation technique will control saphenous vein reflux with less pain and less ecchymosis after surgery. The treatment of varicose veins is less invasive with RFA devices and will become widely accepted as an alternative to conventional surgery for varicose veins in Japan. PMID- 26281656 TI - [SUBFASCIAL ENDOSCOPIC PERFORATOR VEIN SURGERY IN THE TREATMENT OF SEVERE VARICOSE VEINS]. AB - Surgical treatment of severe varicose veins (CEAP classification : C4b-C6) should involve not only interruption of incompetent superficial veins to prevent venous regurgitation due to valve incompetence but also interruption of incompetent perforator veins. Subfascial endoscopic perforator vein surgery (SEPS) is performed via a small skin incision and involves interruption of perforator veins by the insertion of an endoscope into the subfascial space. SEPS produces good surgical outcomes: it is accurate in detecting and transecting perforator veins; has a low frequency of surgical wound complications; prevents lipodermatosclerosis and formation of pigmented skin lesions; and is minimally invasive compared with Linton's operation. Thus, SEPS is an excellent procedure for patients with incompetent perforator veins. SEPS has been covered by the Japanese national health insurance system since April 2014, and it is expected that SEPS will be further developed and become more widespread in use. PMID- 26281658 TI - [PROBLEM AND PERSPECTIVE OF JAPANESE CLINICAL TRIALS]. PMID- 26281659 TI - [STATISTICAL VIEWPOINTS ON DESIGNING INVESTIGATOR INITIATED CLINICAL TRIALS]. PMID- 26281657 TI - [NEGATIVE IMPACT OF THE PARADIGM SHIFT IN THE TREATMENT OF VARICOSE VEINS AND ITS COUNTERMEASURES]. AB - Lower-extremity varicose veins are a representative common condition among the various pathologies that general surgeons are responsible for treating. Their treatment also provides opportunities for students and young physicians to appreciate how interesting the practice of surgery is as well as opportunities for training. Recently, intravenous endoablation has caused a paradigm shift in this important field, resulting in a dramatic decrease in the number of stripping operations performed; a change from inpatient to outpatient care; the introduction of plastic surgeons, dermatologists, and radiologists into this field; and, finally, a change in the place where care is provided (from acute care hospitals to outpatient clinics). If surgeons do not take action, we may lose opportunities to recruit and train young surgeons. To minimize this negative impact, we created a vein clinic that is managed by and for young surgeons in training. Furthermore, we advocate the modification of regulatory hurdles that hamper the performance of endovenous ablation therapy by surgeons. PMID- 26281660 TI - [WHAT WE CAN LEARN FROM A CASE OF MEDICAL MALPRACTICE-PHYSICIANS ACQUITTED OF NEGLIGENCE FOR PRESCRIBING THE DRUG IN QUESTION BECAUSE OF A LEGITIMATE REASON FOR NOT ADHERING TO THE PRECAUTIONS DESCRIBED IN THE PACKAGE INSERTS FOR ALL PRESCRIPTION DRUGS]. PMID- 26281661 TI - [STRICTUREPLASTY FOR STENOTIC LESION OF CROHN'S DISEASE]. PMID- 26281662 TI - [ADVANTAGES AND PROBLEMS OF "SHORT TIME EMPLOYMENT" FOR WOMEN SURGEONS]. PMID- 26281663 TI - [FEMALE SURGEONS SHOULD BE AWARE OF THE IMPORTANCE OF A CLEAR VISION FOR THEIR CAREER AND LIFE PLANS TO ACHIEVE THEIR CAREER DEVELOPMENT.: A SURVEY OF 20 FEMALE SURGEONS AT THE DEPARTMENT OF SURGERY AND ONCOLOGY, KYUSHU UNIVERSITY]. AB - A shortage of surgeons has been a serious problem in recent years. There is an urgent need to utilize female surgeons who tend to resign because of bearing and raising of children. To examine possible measures to deal with the issue, we performed questionnaire survey about work-life balance and career planning on 20 female surgeons in the Department of Surgery and Oncology, Kyushu University. The response rate was 80.0%. In the 16 respondents, seven were unmarried and nine were married. A large fraction of the respondents recognized the importance of work-life-balance. Female surgeons have many difficulties to continue working with good work-life balance; therefore, understanding and cooperation of both their spouses and coworkers is considered to be necessary. Married female surgeons considered that improvement of the working environment and sufficient family support were more important for good work-life balance compared to those who were unmarried. Female surgeons should recognize the importance of improvement of their environment, including the workplace and the family to continue working with good work-life balance in youth and should have the prospects about their career plan of their own. PMID- 26281664 TI - [PROBLEMS OF WORKING FEMALE SURGEONS INVOLVING THEIR FIRST-GRADE ELEMENTARY SCHOOL-AGE CHILDREN: THE FIRST-GRADE BARRIER]. PMID- 26281665 TI - Physician Assistants in the United States--Lessons Learned. PMID- 26281666 TI - [BIOSTATISTICS FOR CANCER CLINICAL TRIALS]. PMID- 26281667 TI - [USEFULNESS OF NATIONAL CLINICAL DATABASE FOR CLINICAL SURGICAL RESEARCH]. PMID- 26281668 TI - [WORLD WIDE CLINICAL TRIALS FROM JAPAN]. PMID- 26281669 TI - [SURGICAL CLINICAL RESEARCH AND WOMEN SURGEONS]. PMID- 26281670 TI - [CLINICAL RESEARCH FOR GENERAL THORACIC SURGERY IN JAPAN]. PMID- 26281671 TI - [SURGICAL CLINICAL STUDY OF ESOPHAGO-GASTRIC JUNCTION CANCER]. PMID- 26281672 TI - [CLINICAL RESEARCH IN THE FIELD OF ENDOSCOPIC SURGERY]. PMID- 26281673 TI - [Bio-imaging and molecular targeted therapy of cancer]. PMID- 26281675 TI - [Targeted molecular therapy based on advanced cancer stem cell model]. AB - Improvement of cell purification and transplantation techniques have contributed to the identification of cell populations known as tumor-initiating cells (TICs). Although it was hypothesized that tumors are organized as hierarchies of tumor cells that are sustained by rare TICs, like normal tissue stem cells, there are several controversies towards such cancer stem cell model, e.g. reversible change of stem cell like population based on epigenetic changes, clonal genetic evolution and problems in xenotransplantation system. Despite complexity in cancer stem cell models, studies in cancer stem cell field have revealed that there are close relationship between cancer malignancy and stem cell properties, called "stemness". Understanding molecular mechanisms for controlling stemness would contribute to establishment of novel diagnostics or therapeutics for cancer. PMID- 26281674 TI - [Discovery and clinical application of mutations in the cancer genome]. AB - Cancer genome/epigenome analyses have identified a wide array of somatic mutations that can confer cancer cell characteristics. These genomic/epigenomic alterations can be targeted for cancer treatment, and, indeed, inhibitors against oncogenic protein-tyrosine kinases have been proved clinically effective. Other types of molecularly targeted therapies, such as epigenetic modifiers, are currently under clinical testing. In addition to the discovery of such driver mutations, profiling of genome/epigenome in cancer becomes especially important in the selection of most appropriate drug in for given cancer patient. PMID- 26281676 TI - [Development of novel epigenetic molecular-targeting agents]. AB - Cancer is known to be a genetic disease, which is caused by abnormalities of oncogenes and/or tumor-suppressor genes. Genetic abnormalities include mutation, deletion or amplification of DNA sequences. Based on the findings of the genetic abnormalities in malignant tumors, many molecular-targeting agents, e.g. Bcr-Abl kinase inhibitors and EGFR kinase inhibitors, have been developed and approved. In addition to genetic abnormalities, epigenetic abnormalities, e.g. DNA methylation, histone methylation and histone acetylation, are also involved in carcinogenesis and tumor development. Based on the findings of the epigenetic abnormalities in malignant tumors, the novel epigenetic molecular-targeting agents, e.g. DNA(DNMT) methyltransferase inhibitors and histone deacetylase (HDAC) inhibitors, have also been developed and approved. Moreover, histone methyltransferase(HMT) inhibitors and histone demethylase(HDM) inhibitors have been also discovered and some agents are in clinical trials. PMID- 26281677 TI - [Metabolomics and molecular targeted therapy of cancer]. AB - Metabolomics is defined as the quantitative measurement of the dynamic multiparametric metabolites. Recent technological advances in the quantification of cellular metabolites, such as capillary electrophoresis (CE) -TOFMS, have prompted the comprehensive analysis of the global metabolism. Now, metabolomics has been used in the identification of new biomarker for toxicology and disease diagnosis, and the elucidation of fermentation processes. Moreover, it is considered that metabolomics would be a powerful tool for the target identification of small molecular bioactive compounds. Here we introduce our recent study that metabolomics was applied to identify the molecular target of glucopiericidin A, which was isolated through a screening of natural products for an inhibitor of cellular filopodia protrusion in carcinoma cells. PMID- 26281678 TI - [Chemical biology and novel molecular-targeted agents in cancer therapy]. AB - Target-based screening and cell-based screening are major approaches to identify anticancer drug candidates. Cell-based screening often contributes to the discovery of first-in-class drugs, but identification of the cellular targets of obtained compounds is a time-consuming step. To overcome this problem, affinity purification with small-molecule probes, which is a classic, but still the most common approach, has become more sophisticated and diversified. In addition, recent advances in omics studies and imaging analyses have allowed us to profile the biological effects of small molecules globally and quantitatively. Consequently, new therapeutic targets/drug leads involved in cancer cell cycle, transcription and redox regulation have been discovered. PMID- 26281679 TI - [Tumor microenvironment: promising therapeutic target]. AB - Tumors are complex tissues composed of cancer cells, various types of stromal cells and extracellular matrix. Recent studies have shown that the tumor microenvironment(TME) plays an important role in both malignant tumor progression and treatment response. Thus, it is essential to improve our understanding of the mechanism of communication between cancer cells and their TME. Much effort has been devoted to developing agents that interfere with the interaction between cancer cells and their TME. In this review, we show a brief overview over the current knowledge about the TME-targeting agents and describe therapeutic strategies that have been designed to target components of the TME. PMID- 26281680 TI - [Isolation and applications of transformation suppressor genes]. AB - A common strategy to identify tumor suppressor genes has been positional cloning, taking advantages of chromosomal abnormalities, linkage to polymorphic markers, etc. We have been taking another approach, based on shotgun cloning with cDNA expression library, to isolate genes suppressing an aspect of transformed phenotypes. Genes identified in such an artificial system, however, require subsequent validation for their clinical relevance through independent approaches, such as finding mutations and altered expression in human cancers. Whether the parental genes act as oncogenes or tumor suppressors needs to be deduced from available annotations and/or new experimental data. Once validated, such genes, being isolated by virtue of their biological activities, are likely to be useful in developing new strategies for tumor prognosis, tumor stratification, and drug discovery. PMID- 26281681 TI - [Therapeutic strategies targeting cancer--specific metabolism]. AB - Basic, clinical and translational metabolic researches in cancer area have been extensively tried to discover and develop novel cancer metabolism drugs. Since tumor cells have metabolic dependencies that distinguish them from their normal counterparts, targeted inhibition of these metabolic dependencies is considered a promising therapeutic strategy against cancer. For example the representative cancer metabolism is that cancer cells exhibit profound metabolic alterations by choosing aerobic glycolysis to metabolize glucose to lactate regardless of the presence of adequate oxygen, although normal cells which mainly utilize glucose by using mitochondrial oxidative phosphorylation to generate ATP. In this review, we focus on several important oncogenes and enzymes, whose alterations have contributed extensively to the metabolic phenotype of cancer cells, with an emphasis on the therapeutic targets. PMID- 26281682 TI - [Development of anti-cancer drugs mediated by apoptosis and autophagy]. AB - Apoptosis and autophagy usually function to eliminate damaged cells and damaged proteins, respectively. Dysfunction of these events induces oncogenesis and cancer development. Therefore, small compounds that activate apoptosis and autophagy are good candidates for anti-cancer chemotherapeutics to combat cancers. This review focuses on recent advances in apoptosis/autophagy and their relationship with tumorigenesis. PMID- 26281683 TI - [Development of biomarkers for molecular target drugs]. AB - In general, the molecular target drugs were superior in the effect, less toxic and realized personalized medicine, resulting in progress in the cancer therapy. The rise in development cost of the molecular target drug and a decrease of the development efficiency become the problem of the drug industry recently. As the solution, development of the excellent biomarker associated with the drug development is considered to be the most important issue. Therefore, the development of the companion diagnostic agent which can evaluate the biomarker precisely is prosperous. A search of the biomarker and the simultaneous development of the companion diagnostic agent enter the mainstream of the development of new molecular target drug. Whereas the process of the drug development is complicated than before. PMID- 26281684 TI - [PI3K and mTOR pathway and molecular targeted agents]. AB - Molecular alteration of PI3K and mTOR pathways is frequently detected in various types of cancers. PIK3CA mutations are the predictive markers for anti-EGFR antibodies, trastuzumab, and lapatinib. The p110 isoform selective PI3K inhibitors has been developed in the clinical settings to reduced off-target induced adverse events. Feedback loop for PI3K signal leads the resistance to PI3K inhibitors. Dual PI3K/mTOR inhibitors and mutation selective PI3K inhibitors are under evaluation to circumvent the resistance. PMID- 26281685 TI - [Kinase inhibitors and their resistance]. AB - Kinase cascades are involved in all stages of tumorigenesis through modulation of transformation and differentiation, cell-cycle progression, and motility. Advances in molecular targeted drug development allow the design and synthesis of inhibitors targeting cancer-associated signal transduction pathways. Potent selective inhibitors with low toxicity can benefit patients especially with several malignancies harboring an oncogenic driver addictive signal. This article evaluates information on solid tumor-related kinase signals and inhibitors, including receptor tyrosine kinase or serine/threonine kinase signals that lead to successful application in clinical settings. In addition, the resistant mechanisms to the inhibitors is summarized. PMID- 26281686 TI - [Cancer therapy by PARP inhibitors]. AB - Poly(ADP-ribose) polymerases(PARP) synthesize the ADP-ribose polymers onto proteins and play a role in DNA repair. PARP inhibitors block the repair of single-strand breaks, which in turn gives rise to double-strand breaks during DNA replication. Thus, PARP inhibitors elicit synthetic lethality in cancer with BRCA1/2 loss-of-function mutations that hamper homologous recombination repair of double-strand breaks. Olaparib, the first-in-class PARP inhibitor, was approved for treatment of BRCA-mutated ovarian cancer in Europe and the United States in 2014. Other PARP inhibitors under clinical trials include rucaparib, niraparib, veliparib, and the "PARP-trapping" BMN-673. BRCA1/2 sequencing is an FDA-approved companion diagnostics, which predicts the cancer vulnerability to PARP inhibition. Together, synthetic lethal PARP inhibition is a novel promising strategy for cancer intervention even in cases without prominent driver oncogenes. PMID- 26281688 TI - [Novel signal transduction pathways: the molecular basis for targeted cancer therapies in Hedgehog/Notch/Wnt pathway]. AB - Aberrant activation of the Wnt, Notch and Hedgehog pathways via mutations or ligand overexpression has been implicated in a large number of cancer types where they are involved in functions ranging from tumor initiation to cancer stem cell (CSC) maintenance and angiogenesis. Agents targeting each one of these three pathways have now reached clinical trials, and the first one of these, Vismodegib, a hedgehog pathway inhibitor, was approved in 2012 by US FDA for the treatment of advanced basal cell carcinoma. Development of agents that target critical steps in these pathways as novel signal transduction pathways will be complicated by signaling cross-talk. The role that embryonic signaling pathways play in the function of CSCs, the development of new anti-CSC therapeutic agents, and the complexity of potential CSC signaling cross-talk are being explored coupled with early phase I clinical studies. PMID- 26281687 TI - [Anti-angiogenesis and molecular targeted therapies]. AB - Tumor angiogenesis contributes to the development of tumor progression. Several vascular endothelial growth factor(VEGF)-targeted agents, administered either as single agents or in combination with chemotherapy, have been shown to benefit patients with advanced-stage malignancies. In particular, bevacizumab is a humanized monoclonal antibody that specifically targets VEGF, inhibiting angiogenesis, thereby impeding tumor growth and survival. It is also possible that combined VEGF and the epidermal growth factor (EGFR) pathway blockade could further enhance antitumor efficacy and help prevent resistance to therapy. Preclinical and clinical studies have shown new various molecular targets and the functional characteristics of tumor angiogenesis, which may provide strategies for improving the therapeutic benefit. PMID- 26281689 TI - [Impact of molecular targeting therapy on tumor immunity]. AB - Emerging evidence has been unveiled that major oncogenic pathways, which serve as a main focus for the molecular targeting therapies, play a pivotal role in establishing immunosuppressive tumor microenvironments. The modulation of various immune modulatory pathways, such as upregulation of PD-L1 by various oncogenic mutations such as EGFR, BRAF, activation of PI3K and JAK-Stat3 on tumor cells, may be critical in modulating tumor immune responses. Given the potential clinical impact of immune checkpoint blockade and other immunotherapeutic regimens as a future anticancer regimen, it is critical to clarify the mechanisms by which molecularly targetable oncogenes and tumor microenvironments influence quality of tumor immunosurveillance, which should provide a new strategy for suitable combinatorial approaches composing of molecular targeting and immunotherapies. PMID- 26281690 TI - [Pharmacokinetic issues on cancer pharmacotherapy]. AB - Efficacy of cancer pharmacotherapy depends upon drug exposure to the body and responsiveness of the tumor to the drug treatment. Drug exposure is determined by pharmacokinetics and dose, whereas responsiveness is intrinsically variable by tumor heterogeneity. Molecular targeting drugs are used as promising therapy for cancers, and most of them are coupled with particular diagnostics which can predict responders and non-responders before treatment. On the other hand, lower drug exposure to the body can lead to insufficient efficacy. A number of important evidences have been published recently on exposure-response relationships for molecular targeting drugs including monoclonal antibodies and small molecules. In this chapter, two examples are presented; anti-HER2 antibody and tyrosine kinase inhibitor. Patients with the lowest trough concentrations of trastuzumab in cycle 1 showed shorter overall survival in metastatic gastric cancer study. Efficacy of imatinib in chronic myelogenous leukemia depended on plasma concentration of imatinib, and therapeutic drug monitoring (TDM) of imatinib is expected to improve the therapeutic outcome in CML. PMID- 26281691 TI - [Molecular targeted therapy and genomic evolution of breast cancer]. AB - Owing to development of next generation sequencer (NGS), deep biological insights of breast cancer have been provided. Information of genomic mutations and rearrangements in patients' tumors is required to understand the mechanism in resistance of molecular targeted medicine. To date, NGS analyses illustrated not only base substitution patterns and lists of driver mutations and key rearrangements, but also a manner of tumor evolution. Breast cancer genome is dynamically changing and evolving during cancer development course and treatment procedures. Liquid biopsy is a non-invasive method to detect the genomic evolution of breast cancer, which is now under development for future application to clinical practice of cancer treatment. In this article, latest knowledge regarding breast cancer genome, especially in terms of 'evolution', is summarized. PMID- 26281692 TI - [Challenge of gene-based personalized lung cancer medicine]. AB - Up to the present, several genes have been identified as drivers for lung carcinogenesis, and their aberrations have been shown to be linked with differential response to therapy. Optimized treatments are, therefore, important in the situation that we have options for treatments by driver gene aberrations. Recently, comprehensive analyses of DNA and RNA from lung tumor tissues have been actively performed and have been pushing the lung cancer medicine forwards. In addition, circulating cell-free tumor DNA in plasma as a "liquid biopsy" opens a great hope for noninvasive molecular diagnosis. This article will highlight findings of recent comprehensive genome analysis to improve precision lung cancer medicine. PMID- 26281693 TI - [Molecular mechanisms of targeted drug resistance in lung cancer and its therapeutic strategy]. AB - Several driver oncogenes, including EGFR mutations and ALK rearrangement, have been identified in lung cancer. The EGFR tyrosine kinase inhibitors (TKIs) and ALK-TKIs show dramatic effects against lung cancer with EGFR activating mutations and ALK rearrangements, respectively. However, 20% of EGFR mutant lung cancer patients show intrinsic resistance, and the responders almost invariably acquire resistance to EGFR-TKIs within several years. Several mechanisms, including secondary mutations in EGFR or ALK, activation of alternative pathway, have been reported to contribute to resistance to EGFR-TKIs and ALK-TKIs. New generation TKIs for overcoming resistance to EGFR-TKI or ALK-TKI are being evaluated in clinical trials. Further investigations to develop optimal therapy based on accurate diagnosis of resistant mechanism are warranted to improve the success of treatment with targeted drugs in lung cancer. PMID- 26281694 TI - [Targeted therapies for metastatic colorectal cancer]. AB - Targeted therapies against vascular endothelial growth factor (VEGF), VEGF receptor and epidermal growth factor receptor (EGFR) have improved survival in patients with metastatic colorectal cancer (mCRC). Clinical studies have demonstrated that the following 6 targeted agents showed antitumor activity in patients with mCRC: bevacizumab, aflibercept, ramucirumab, cetuximab, panitumumab and regorafenib. KRAS exon 2 (codons 12 and 13) mutations were negative predictive biomarkers for efficacy of anti-EGFR antibody therapy. Expanded RAS mutations (including KRAS exon 2, exon 3 and exon 4 mutations as well as NRAS mutations) can further predict the therapeutic effects of this therapy. It seems to be necessary to identify new predictive biomarkers and develop new targeted agents for personalized treatment for mCRC. PMID- 26281695 TI - [Molecular target therapies for skin cancers]. AB - Over the three decades, advances in the fields of cancer genetics and immunology have elucidated mechanisms that cause the growth of cutaneous malignancies. This has contributed to the rational design of molecular target therapies. In this review, the molecular pathways and cancer immunology critical to the development of cutaneous malignancies are discussed. Included is a review of the following novel pharmacologic agents; BRAF inhibitors, MEK inhibitors, anti-CTLA-4 antibody and anti-PD-1 antibodies for melanoma, cetuximab and gefitinib for squamous cell carcinoma, vismodegib for basal cell carcinoma and nevoid basal cell carcinoma syndrome, imiquimod for extramammary Paget's disease, imatinib for dermatofibrosarcoma protuberans and vorinostat and mogamulizumab for cutaneous T cell lymphoma. PMID- 26281696 TI - [Molecular targeted drugs for soft tissue sarcoma and neuroendocrine tumor]. AB - Both the soft tissue sarcomas and the neuroendocrine tumors are rare diseases. Therefore the recruiting of these patients was more difficult than other cancer species, and the development of the new therapy for these diseases did not readily advance. However, the identification of driver molecules for each sub type enabled us to the development of the molecular targeted drugs. As for the GIST, several TKIs are used, but in late years it is found that susceptibility of TKIs varies according to difference in second mutation. In this chapter, the molecular target drug for the soft tissue sarcoma and the neuroendocrine tumor is reviewed. PMID- 26281697 TI - [International comparison and regulatory issues of the molecular targeted therapy development]. AB - In July 2013 from the Ministry of Health, Labour and Welfare of Japan notified "Approval application for in vitro companion diagnostics and corresponding therapeutic products" (manager notification). They recommended concurrent development of molecular targeted therapies and companion diagnostics. However, there are specific difficulties; cooperation between diagnostic company and pharmaceutical company, indeterminacy of profitability outlook etc. Moreover, it is also a problem how to supervise and to secure the quality and safety of the examination. In the future, multiplex diagnostic examination, which detect multiple molecular targets abnormalities at once, is developed commercially. In this paper, we outline the issues as well as international comparison in the current state of the approval and application system. PMID- 26281698 TI - [Pathologic characteristics of malignant neoplasms occurring in the elderly]. AB - Malignant neoplasm preferentially occurs in the elderly. Common cancers in the elderly are gastric, colorectal, lung and prostate cancers in men whereas colorectal, lung, gastric and pancreatic cancers in women. There are several characteristic features such as tumor location, histology, biological behavior and pathway of carcinogenesis in malignant neoplasms occurring in the elderly. Multiple cancers increase with aging. Although it is generally believed that carcinoma in the elderly shows well differentiation, slow growth, low incidence of metastasis and favorable prognosis, the tumor does not always show such features. Regarding biological behavior of malignant tumor in the elderly, age related alterations of the host such as stromal weakness and decreased immune response against cancer cell invasion should be considered as well as characteristics of tumor cell itself. Thus, we need a specific strategy for treatment for malignant neoplasms in the elderly. PMID- 26281699 TI - [Targeted therapy for solid tumors in the elderly]. AB - The majority of cancer incidences and deaths occur in the elderly. Elderly patients are a heterogeneous population in terms of physical reserve, comorbidity, polypharmacy, and other geriatric conditions. The elderly has been under-represented in clinical trials of cancer therapy, even in the era of targeted therapy. It is widely believed that targeted therapy, which interferes with specific pathways required for tumor development and growth, is more effective and less toxic than cytotoxic chemotherapy. However, some toxicities are concerned in the elderly such as arterial thromboembolism associated with the use of bevacizumab and cardiotoxicity with trastuzumab. This article reviews the available evidence on the efficiency and toxicity of targeted therapy for solid tumors in the elderly. PMID- 26281701 TI - Face the change. PMID- 26281702 TI - A year of self-discovery. PMID- 26281700 TI - [Current status and future prospects of research on Fukuyama muscular dystrophy]. AB - Fukuyama congenital muscular dystrophy(FCMD) is a second common childhood muscular dystrophy in Japan. All FCMD patients have ancestral insertion of the SVA retrotransposal element into fukutin. We show that aberrant mRNA splicing induced by SVA exon-trapping caused FCMD. Introduction of 3 cocktailed antisense oligonucleotides(AONs) targeting around these splice sites prevented pathogenic splicing in FCMD patient cells and model mice, and normalized protein production and functions of Fukutin as well as O-glycosylation of alpha-dystroglycan. We show the promise of splicing modulation therapy as the first radical clinical treatment for FCMD in the near future. We also show that fukutin is prerequisite to ameliorate muscular dystrophic phenotype by myofiber-selective LARGE expression. Recent advances in FCMD are discussed. PMID- 26281703 TI - Coming home. PMID- 26281704 TI - Follow the clues ... EVIDENTALY. PMID- 26281705 TI - Dental transitions. PMID- 26281706 TI - Sleep apnoea for the dental practitioner. PMID- 26281707 TI - Smoking cessation and the role of the dental practitioner. AB - As dentists we are uniquely positioned to influence the rate of tobacco smoking and could contribute to a decrease in the associated mortality and morbidity. The detrimental effects of smoking on oral health are well established; thus, a structured approach to initiate smoking cessation, help to manage the initial phase of withdrawal symptoms, and provide long-term support is an important role for our profession. It has been shown that smoking cessation advice for even a few minutes increases long-term smoking abstinence rates by 5%, which can be increased by 50-70% with the use of adjunctive pharmacotherapy, e.g., nicotine replacement therapy, for withdrawal symptoms. This article aims to give a brief overview of smoking in relation to oral health, review the management of tobacco smoking dependence, and discuss how we as dentists can help our patients to quit smoking. PMID- 26281708 TI - Mandibular implant-supported overdentures: attachment systems, and number and locations of implants--Part I. AB - The use of dental implants in replacing missing teeth is an integral part of restorative dental treatment. Use of conventional complete dentures is associated with several problems such as lack of denture stability, support and retention. However, when mandibular complete dentures were used with two or more implants, an improvement in the patients' psychological and social well-being could be seen. There is general consensus that removable implant-supported overdentures (RISOs) with two implants should be considered as the first-choice standard of care for an edentulous mandible. This treatment option necessitates the use of attachment systems that connect the complete denture to the implant. Nevertheless, each attachment system has its inherent advantages and disadvantages, which should be considered when choosing a system. The first part of this article provides an overview on options available to restore the mandibular edentulous arch with dental implants. Different types of attachment systems, their features and drawbacks are also reviewed. PMID- 26281709 TI - Characterization of the Catalytic Domain of Human APOBEC3B and the Critical Structural Role for a Conserved Methionine. AB - Human APOBEC3B deaminates cytosines in DNA and belongs to the AID/APOBEC family of enzymes. These proteins are involved in innate and adaptive immunity and may cause mutations in a variety of cancers. To characterize its ability to convert cytosines into uracils, we tested several derivatives of APOBEC3B gene for their ability to cause mutations in Escherichia coli. Through this analysis, a methionine residue at the junction of the amino-terminal domain (NTD) and the carboxy-terminal domain (CTD) was found to be essential for high mutagenicity. Properties of mutants with substitutions at this position, examination of existing molecular structures of APOBEC3 family members and molecular modeling suggest that this residue is essential for the structural stability of this family of proteins. The APOBEC3B CTD with the highest mutational activity was purified to homogeneity and its kinetic parameters were determined. Size exclusion chromatography of the CTD monomer showed that it is in equilibrium with its dimeric form and matrix-assisted laser desorption ionization time-of-flight analysis of the protein suggested that the dimer may be quite stable. The partially purified NTD did not show intrinsic deamination activity and did not enhance the activity of the CTD in biochemical assays. Finally, APOBEC3B was at least 10-fold less efficient at mutating 5-methylcytosine (5mC) to thymine than APOBEC3A in a genetic assay and was at least 10-fold less efficient at deaminating 5mC compared to C in biochemical assays. These results shed light on the structural organization of APOBEC3B catalytic domain, its substrate specificity and its possible role in causing genome-wide mutations. PMID- 26281710 TI - beta-Structure within the Denatured State of the Helical Protein Domain BBL. AB - Protein denatured states are the origin of both healthy and toxic conformational species. Denatured states of ultrafast folding proteins are of interest in mechanistic studies because they are energetically close to the kinetic bottleneck of folding. However, their transient nature makes them elusive to experiment. Here, we generated the denatured state of the helical domain BBL that is poised to fold in microseconds by a single-point mutation and combined circular dichroism spectroscopy, single-molecule fluorescence fluctuation analysis, and computer simulation to characterize its structure and dynamics. Circular dichroism showed a largely unfolded ensemble with marginal helix but significant beta-sheet content. Main-chain structure and dynamics were unaffected by side-chain interactions that stabilize the native state, as revealed by site directed mutagenesis and nanosecond loop closure kinetics probed by fluorescence correlation spectroscopy. Replica-exchange and constant-temperature molecular dynamics simulations showed a highly collapsed, hydrogen-bonded denatured state containing turn and beta-sheet structure and few nucleating helices in an otherwise unfolded ensemble. An irregular beta-hairpin element that connects helices in the native fold was poised to be formed. The surprising observation of beta-structure in regions that form helices in the native state is reconciled by a generic low-energy pathway from the northwest quadrant of Ramachandran space to the helical basin present under folding conditions, proposed recently. Our results show that, indeed, rapid nucleation of helix emanates from beta-structure formed early within a collapsed ensemble of unfolded conformers. PMID- 26281711 TI - Selection of High-Affinity Peptidic Serine Protease Inhibitors with Increased Binding Entropy from a Back-Flip Library of Peptide-Protease Fusions. AB - We have developed a new concept for designing peptidic protein modulators, by recombinantly fusing the peptidic modulator, with randomized residues, directly to the target protein via a linker and screening for internal modulation of the activity of the protein. We tested the feasibility of the concept by fusing a 10 residue-long, disulfide-bond-constrained inhibitory peptide, randomized in selected positions, to the catalytic domain of the serine protease murine urokinase-type plasminogen activator. High-affinity inhibitory peptide variants were identified as those that conferred to the fusion protease the lowest activity for substrate hydrolysis. The usefulness of the strategy was demonstrated by the selection of peptidic inhibitors of murine urokinase-type plasminogen activator with a low nanomolar affinity. The high affinity could not have been predicted by rational considerations, as the high affinity was associated with a loss of polar interactions and an increased binding entropy. PMID- 26281712 TI - Seed bank characteristics of the Nymphoides peltata population in Lake Taihu. AB - The Nymphoides peltata (N. peltata) population has shown rapid expansion in Lake Taihu, China, in recent years. The core question is whether N. peltata seeds have contributed to the expansion. To address this, we randomly selected three N. peltata stands to investigate the seed bank characteristics of N. peltata in Lake Taihu. Results showed that N. peltata had high seed production, with a maximum seed yield of 1763 seeds per m(2). Density of intact and fragmented seeds decreased rapidly with sediment depth. Few intact or fragmented seeds were distributed at depths greater than 4 cm in the sediment. Spatial distribution of the seed bank indicated that most seeds sank to the sediment within the N. peltata stands, and few seeds took advantage of their floating ability. Seeds recovered from the sediment during April to June had a low germination rate, and no seeds germinated during October to April. Cold exposure treatment increased the germination rate remarkably. No seedlings were found in the field from January 2012 to December 2012, indicating that few seeds were successfully established in the surveyed area. The results suggested that sexual reproduction had little direct contribution to the N. peltata expansion in this large shallow lake. PMID- 26281713 TI - Low incidence of CALR gene mutations in patients with cerebral venous thrombosis without overt chronic myeloproliferative neoplasm. PMID- 26281714 TI - Using six-colour flow cytometry to analyse the activation and interaction of platelets and leukocytes--A new assay suitable for bench and bedside conditions. AB - INTRODUCTION: Platelets are main effector cells in haemostasis and also promote inflammation. Platelet-leukocyte complexes are key mediators in a variety of thromboinflammatory disorders and consecutive organ failure. Cell-specific epitopes and activation markers on platelets and leukocytes can be measured using flow cytometry. However, until recently a major restriction has been a paucity in antibody combinations and lack of detection strategies. We aimed to develop a six colour flow cytometry method which depicts multiple aspects of platelet and leukocyte interactions in human whole blood. MATERIALS AND METHODS: Platelets, including microparticles and aggregates, were detected in flow cytometry using a platelet-specific anti-CD41-FITC antibody and size-defined regions. The morphology of platelet-leukocyte complexes (including granulocyte and monocyte content) were depicted using anti-CD45-PerCP, anti-CD66b-PE-Cy7, and anti-CD14 APC antibodies in a single sample. Expression of platelet and leukocyte activation markers P-selectin and CD11b were detected using anti-CD62P-PE and anti-CD11b-BV421 antibodies, respectively. RESULTS: The sensitivity of this assay to detect the effects of various agonists (TRAP-6, ADP, collagen, epinephrine, TNF-alpha and LPS) is demonstrated. Furthermore, the assay is shown to detect platelet and leukocyte activation induced by extracorporeal circulation in vitro. The suitability of this assay for bedside analysis is demonstrated exemplarily in a patient treated with mechanical circulatory life support. CONCLUSIONS: Using the concurrent assessment of multiple parameters, this method gives detailed insights into the complexity and dynamics of platelet-leukocyte interactions. This assay carries the potential to increase our understanding of the mechanisms and pathophysiology of platelet-leukocyte interaction in the research laboratory and clinical setting. PMID- 26281715 TI - Low Dopamine D2 Receptor Increases Vulnerability to Obesity Via Reduced Physical Activity, Not Increased Appetitive Motivation. AB - BACKGROUND: The dopamine D2 receptor (D2R) has received much attention in obesity studies. Data indicate that D2R is reduced in obesity and that the TaqA1 D2R variant may be more prevalent among obese persons. It is often suggested that reduced D2R generates a reward deficiency and altered appetitive motivation that induces compulsive eating and contributes to obesity. Although dopamine is known to regulate physical activity, it is often neglected in these studies, leaving open the question of whether reduced D2R contributes to obesity through alterations in energy expenditure and activity. METHODS: We generated a D2R knockdown (KD) mouse line and assessed both energy expenditure and appetitive motivation under conditions of diet-induced obesity. RESULTS: The KD mice did not gain more weight or show increased appetitive motivation compared with wild-type mice in a standard environment; however, in an enriched environment with voluntary exercise opportunities, KD mice exhibited dramatically lower activity and became more obese than wild-type mice, obtaining no protective benefit from exercise opportunities. CONCLUSIONS: These data suggest the primary contribution of altered D2R signaling to obesity lies in altered energy expenditure rather than the induction of compulsive overeating. PMID- 26281718 TI - [Tele-cooperation for innovative care using the example of the University Hospital Aachen. Telematics in intensive care medicine, emergency medicine, and telemedical intersectoral rehabilitation planning in geriatric trauma]. AB - The demographic challenge of the ageing society is associated with increasing comorbidity. On the other hand, there will be an ageing workforce in medicine, resulting in an imbalance between the demand and supply of medical care in the near future. In rural areas in particular, this imbalance is already present today. Based on three best practice projects carried out by our telemedical center in Aachen, including emergency medicine, intensive care medicine, and the rehabilitation planning of geriatric trauma care, some experience and the potential of the intersectoral provision of care, supported by telemedicine, are demonstrated. Telemedicine is the provision of medical services over a geographical distance by using tele-communication and data transfer. It has been proven to ensure a constant quality of health care. Telemedical support enables shared expertise independent of time and space, and allows efficient allocation of resources. A review of international experience supports this notion. PMID- 26281717 TI - Sympathetic Release of Splenic Monocytes Promotes Recurring Anxiety Following Repeated Social Defeat. AB - BACKGROUND: Neuroinflammatory signaling may contribute to the pathophysiology of chronic anxiety disorders. Previous work showed that repeated social defeat (RSD) in mice promoted stress-sensitization that was characterized by the recurrence of anxiety following subthreshold stress 24 days after RSD. Furthermore, splenectomy following RSD prevented the recurrence of anxiety in stress-sensitized mice. We hypothesize that the spleen of RSD-exposed mice became a reservoir of primed monocytes that were released following neuroendocrine activation by subthreshold stress. METHODS: Mice were subjected to subthreshold stress (i.e., single cycle of social defeat) 24 days after RSD, and immune and behavioral measures were taken. RESULTS: Subthreshold stress 24 days after RSD re-established anxiety-like behavior that was associated with egress of Ly6C(hi) monocytes from the spleen. Moreover, splenectomy before RSD blocked monocyte trafficking to the brain and prevented anxiety-like behavior following subthreshold stress. Splenectomy, however, had no effect on monocyte accumulation or anxiety when determined 14 hours after RSD. In addition, splenocytes cultured 24 days after RSD exhibited a primed inflammatory phenotype. Peripheral sympathetic inhibition before subthreshold stress blocked monocyte trafficking from the spleen to the brain and prevented the re-establishment of anxiety in RSD-sensitized mice. Last, beta adrenergic antagonism also prevented splenic monocyte egress after acute stress. CONCLUSIONS: The spleen served as a unique reservoir of primed monocytes that were readily released following sympathetic activation by subthreshold stress that promoted the re-establishment of anxiety. Collectively, the long-term storage of primed monocytes in the spleen may have a profound influence on recurring anxiety disorders. PMID- 26281716 TI - Abnormal Gamma Oscillations in N-Methyl-D-Aspartate Receptor Hypofunction Models of Schizophrenia. AB - N-methyl-D-aspartate receptor (NMDAR) hypofunction in parvalbumin-expressing (PV+) inhibitory neurons (INs) may contribute to symptoms in patients with schizophrenia (SZ). This hypothesis was inspired by studies in humans involving NMDAR antagonists that trigger SZ symptoms. Animal models of SZ using neuropharmacology and genetic knockouts have successfully replicated some of the key observations in human subjects involving alteration of gamma band oscillations (GBO) observed in electroencephalography and magnetoencephalography signals. However, it remains to be seen if NMDAR hypofunction in PV+ neurons is fundamental to the phenotype observed in these models. In this review, we discuss some of the key computational models of GBO and their predictions in the context of NMDAR hypofunction in INs. While PV+ INs have been the main focus of SZ studies in animal models, we also discuss the implications of NMDAR hypofunction in other types of INs using computational models for GBO modulation in the visual cortex. PMID- 26281719 TI - Methane Emissions from United States Natural Gas Gathering and Processing. AB - New facility-level methane (CH4) emissions measurements obtained from 114 natural gas gathering facilities and 16 processing plants in 13 U.S. states were combined with facility counts obtained from state and national databases in a Monte Carlo simulation to estimate CH4 emissions from U.S. natural gas gathering and processing operations. Total annual CH4 emissions of 2421 (+245/-237) Gg were estimated for all U.S. gathering and processing operations, which represents a CH4 loss rate of 0.47% (+/-0.05%) when normalized by 2012 CH4 production. Over 90% of those emissions were attributed to normal operation of gathering facilities (1697 +189/-185 Gg) and processing plants (506 +55/-52 Gg), with the balance attributed to gathering pipelines and processing plant routine maintenance and upsets. The median CH4 emissions estimate for processing plants is a factor of 1.7 lower than the 2012 EPA Greenhouse Gas Inventory (GHGI) estimate, with the difference due largely to fewer reciprocating compressors, and a factor of 3.0 higher than that reported under the EPA Greenhouse Gas Reporting Program. Since gathering operations are currently embedded within the production segment of the EPA GHGI, direct comparison to our results is complicated. However, the study results suggest that CH4 emissions from gathering are substantially higher than the current EPA GHGI estimate and are equivalent to 30% of the total net CH4 emissions in the natural gas systems GHGI. Because CH4 emissions from most gathering facilities are not reported under the current rule and not all source categories are reported for processing plants, the total CH4 emissions from gathering and processing reported under the EPA GHGRP (180 Gg) represents only 14% of that tabulated in the EPA GHGI and 7% of that predicted from this study. PMID- 26281721 TI - Multiple Nonthermal Reaction Steps for the Photooxidation of CO to CO2 on Reduced TiO2(110). AB - The photooxidation of CO on reduced, rutile TiO2(110) is studied on a millisecond time scale. For CO coadsorbed with a saturation coverage of chemisorbed O2 (thetasat), the CO2 photon-stimulated desorption (PSD) signal is initially zero, increases to a maximum after several tens of milliseconds, and then decreases at longer times. The initial CO2 PSD signal increases ~5 times more quickly for an oxygen coverage of 0.5thetasat. The initial rate of increase of the CO2 PSD signal is proportional to the flux of UV photons. The results show that two or more nonthermal reaction steps are required to photooxidize CO adsorbed on TiO2(110). The intermediate species involved in the reactions is stable for at least 100 s at 30 K. Previous models had suggested that CO photooxidation required only one nonthermal reaction. The likely initial and final charge states of the system suggest that an electron-mediated reaction and a hole-mediated reaction are needed for the complete photooxidation reaction. PMID- 26281722 TI - Unconventional Peroxy Chemistry in Alcohol Oxidation: The Water Elimination Pathway. AB - Predictive simulation for designing efficient engines requires detailed modeling of combustion chemistry, for which the possibility of unknown pathways is a continual concern. Here, we characterize a low-lying water elimination pathway from key hydroperoxyalkyl (QOOH) radicals derived from alcohols. The corresponding saddle-point structure involves the interaction of radical and zwitterionic electronic states. This interaction presents extreme difficulties for electronic structure characterizations, but we demonstrate that these properties of this saddle point can be well captured by M06-2X and CCSD(T) methods. Experimental evidence for the existence and relevance of this pathway is shown in recently reported data on the low-temperature oxidation of isopentanol and isobutanol. In these systems, water elimination is a major pathway, and is likely ubiquitous in low-temperature alcohol oxidation. These findings will substantially alter current alcohol oxidation mechanisms. Moreover, the methods described will be useful for the more general phenomenon of interacting radical and zwitterionic states. PMID- 26281723 TI - Engineered CuInSexS2-x Quantum Dots for Sensitized Solar Cells. AB - Colloidal CuInSexS2-x quantum dots (QDs) are an attractive less-toxic alternative to PbX and CdX (X = S, Se, and Te) QDs for solution-processed semiconductor devices. This relatively new class of QD materials is particularly suited to serving as an absorber in photovoltaics, owing to its high absorption coefficient and near-optimal and finely tunable band gap. Here, we engineer CuInSexS2-x QD sensitizers for enhanced performance of QD-sensitized TiO2 solar cells (QDSSCs). Our QD synthesis employs 1-dodecanethiol (DDT) as a low-cost solvent, which also serves as a ligand, and a sulfur precursor; addition of triakylphosphine selenide leads to incorporation of controlled amounts of selenium, reducing the band gap compared to that of pure CuInS2 QDs. This enables significantly higher photocurrent in the near-infrared (IR) region of the solar spectrum without sacrificing photovoltage. In order to passivate QD surface recombination centers, we perform a surface-cation exchange with Cd prior to sensitization, which enhances chemical stability and leads to a further increase in photocurrent. We use the synthesized QDs to demonstrate proof-of-concept QDSSCs with up to 3.5% power conversion efficiency. PMID- 26281724 TI - Does Coherence Enhance Transport in Photosynthesis? AB - Recent observations of coherence in photosynthetic complexes have led to the question of whether quantum effects can occur in vivo, not under femtosecond laser pulses but in incoherent sunlight and at steady state, and, if so, whether the coherence explains the high exciton transfer efficiency. We introduce the distinction between state coherence and process coherence and show that although some photosynthetic pathways are partially coherent processes, photosynthesis in nature proceeds through stationary states. This distinction allows us to rule out several mechanisms of transport enhancement in sunlight. In particular, although they are crucial for understanding exciton transport, neither wavelike motion nor microscopic coherence, on their own, enhance the efficiency. By contrast, two partially coherent mechanisms-ENAQT and supertransfer-can enhance transport even in sunlight and thus constitute motifs for the optimization of artificial sunlight harvesting. Finally, we clarify the importance of ultrafast spectroscopy in understanding incoherent processes. PMID- 26281725 TI - Highly Efficient Pumping of Vibrationally Excited HD Molecules via Stark-Induced Adiabatic Raman Passage. AB - A primary prerequisite to study reactivity of vibrationally excited species is to efficiently prepare reacting species in a well-defined vibrational level. Efficient pumping of IR active vibrational modes in a molecule can be achieved by direct IR absorption. For vibrational modes that are only Raman active, however, efficient preparation of vibrationally excited states in those modes is not easily attainable. In this work, we have shown that highly efficient preparation of the HD(v = 1) state using the Stark-induced adiabatic Raman passage (SARP) scheme is feasible. As high as 91% population transfer from v = 0 to 1 of HD has been demonstrated in our experiment. This method provides new opportunities for future experimental studies on the dynamics of vibrational state molecules, especially H2, in both gas-phase and beam-surface reactions. PMID- 26281726 TI - Spatial and Electronic Correlations in the PE545 Light-Harvesting Complex. AB - The recent discovery of long-lasting quantum coherence effects in photosynthetic pigment-protein complexes has challenged our view of the role that protein motions play in light-harvesting processes. Several groups have suggested that correlated fluctuations involving the pigments site energies and couplings could be at the origin of such unexpected behavior. Here we combine molecular dynamics simulations with quantum mechanics/molecular mechanics calculations to analyze the degree of correlated fluctuations in the PE545 complex of Rhodomonas sp. strain CS24. We find that correlations between the motions of the chromophores, which are significantly assisted by the water solvent, do not translate into appreciable site energy correlations but do lead to significant cross correlations of energies and couplings. Such behavior, not observed in a recent study on the Fenna-Mathews-Olson complex, seems to provide phycobiliproteins with an additional fundamental mechanism to control quantum coherence and light harvesting efficiency compared with chlorophyll-containing complexes. PMID- 26281727 TI - Monolayer to Bilayer Structural Transition in Confined Pyrrolidinium-Based Ionic Liquids. AB - Ionic liquids can be intricately nanostructured in the bulk and at interfaces resulting from a delicate interplay between interionic and surface forces. Here we report the structuring of a series of dialkylpyrrolidinium-based ionic liquids induced by confinement. The ionic liquids containing cations with shorter alkyl chain substituents form alternating cation-anion monolayer structures on confinement to a thin film, whereas a cation with a longer alkyl chain substituent leads to bilayer formation. The crossover from monolayer to bilayer structure occurs between chain lengths of n = 8 and 10 for these pyrrolidinium based ionic liquids. The bilayer structure for n = 10 involves full interdigitation of the alkyl chains; this is in contrast with previous observations for imidazolium-based ionic liquids. The results are pertinent to these liquids' application as electrolytes, where the electrolyte is confined inside the pores of a nanoporous electrode, for example, in devices such as supercapacitors or batteries. PMID- 26281728 TI - Coherent High-Frequency Vibrational Dynamics in the Excited Electronic State of All-Trans Retinal Derivatives. AB - Coherent vibrational dynamics of retinal in excited electronic states are of primary importance in the understanding of photobiology. Using pump-DFWM, we demonstrate for the first time the existence of coherent double-bond high frequency modulations (>1300 cm(-1)) in the excited electronic state of different retinal derivatives. All-trans retinal as well as retinal Schiff bases exhibit a partial frequency downshift of the C?C double-bond mode from ~1580 cm(-1) in the ground state to 1510 cm(-1) in the excited state. In addition, a new vibrational band at ~1700 cm(-1) assigned to the C?N stretching mode in retinal Schiff bases in the excited state is detected. The newly reported bands are observed only in specific spectral regions of excited-state absorption. Implications regarding the observation of vibrational coherences in naturally occurring retinal protonated Schiff bases in rhodopsins are discussed. PMID- 26281729 TI - Understanding Trends in the Electrocatalytic Activity of Metals and Enzymes for CO2 Reduction to CO. AB - We develop a model based on density functional theory calculations to describe trends in catalytic activity for CO2 electroreduction to CO in terms of the adsorption energy of the reaction intermediates, CO and COOH. The model is applied to metal surfaces as well as the active site in the CODH enzymes and shows that the strong scaling between adsorbed CO and adsorbed COOH on metal surfaces is responsible for the persistent overpotential. The active site of the CODH enzyme is not subject to these scaling relations and optimizes the relative binding energies of these adsorbates, allowing for an essentially reversible process with a low overpotential. PMID- 26281730 TI - Physical Chemistry Research Toward Proton Exchange Membrane Fuel Cell Advancement. AB - Hydrogen fuel cells, the most common type of which are proton exchange membrane fuel cells (PEMFCs), are on a rapid path to commercialization. We credit physical chemistry research in oxygen reduction electrocatalysis and theory with significant breakthroughs, enabling more cost-effective fuel cells. However, most of the physical chemistry has been restricted to studies of platinum and related alloys. More work is needed to better understand electrocatalysts generally in terms of properties and characterization. While the advent of such highly active catalysts will enable smaller, less expensive, and more powerful stacks, they will require better understanding and a complete restructuring of the diffusion media in PEMFCs to facilitate faster transport of the reactants (O2) and products (H2O). Even Ohmic losses between materials become more important at high power. Such lessons from PEMFC research are relevant to other electrochemical conversion systems, including Li-air batteries and flow batteries. PMID- 26281731 TI - Efficient Dual-Modal NIR-to-NIR Emission of Rare Earth Ions Co-doped Nanocrystals for Biological Fluorescence Imaging. AB - A novel approach has been developed for the realization of efficient near infrared to near-infrared (NIR-to-NIR) upconversion and down-shifting emission in nanophosphors. The efficient dual-modal NIR-to-NIR emission is realized in a beta NaGdF4/Nd(3+)@NaGdF4/Tm(3+)-Yb(3+) core-shell nanocrystal by careful control of the identity and concentration of the doped rare earth (RE) ion species and by manipulation of the spatial distributions of these RE ions. The photoluminescence results reveal that the emission efficiency increases at least 2-fold when comparing the materials synthesized in this study with those synthesized through traditional approaches. Hence, these core-shell structured nanocrystals with novel excitation and emission behaviors enable us to obtain tissue fluorescence imaging by detecting the upconverted and down-shifted photoluminescence from Tm(3+) and Nd(3+) ions, respectively. The reported approach thus provides a new route for the realization of high-yield emission from RE ion doped nanocrystals, which could prove to be useful for the design of optical materials containing other optically active centers. PMID- 26281732 TI - Tunable Infrared Phosphors Using Cu Doping in Semiconductor Nanocrystals: Surface Electronic Structure Evaluation. AB - In this Letter, we report the study of the effect of ligands on the surface electronic structure of the nanocrystal by exploiting the mechanism of the Cu related optical transition, obtained by coupling the nanocrystal conduction band to the Cu ion state in Cu-doped II-VI semiconductor nanocrystals. Systematic study of steady-state luminescence and lifetime decay dynamics of this Cu-related emission in cadmium-based chalcogenides shows that the role of oleic acid in surface passivation is unexpectedly quite different for various chalcogenides. Further, using these leads in Cu-doped CdS nanocrystals, we develop near-infrared emitting phosphor materials that have tunable, high quantum yield (~35%) emission with a single-exponential lifetime decay. Surprisingly, unlike the emission from other Cu-doped II-VI nanocrystals, emission from Cu doping in CdS nanocrystals is found to exhibit high thermal stability, being essentially unchanged up to 100 degrees C, making them more viable for use in various practical applications. PMID- 26281733 TI - Surface Chemistry Exchange of Alloyed Germanium Nanocrystals: A Pathway Toward Conductive Group IV Nanocrystal Films. AB - We present an expansion of the mixed-valence iodide reduction method for the synthesis of Ge nanocrystals (NCs) to incorporate low levels (~1 mol %) of groups III, IV, and V elements to yield main-group element-alloyed Ge NCs (Ge1-xEx NCs). Nearly every main-group element (E) that surrounds Ge on the periodic table (Al, P, Ga, As, In, Sn, and Sb) may be incorporated into Ge1-xEx NCs with remarkably high E incorporation into the product (>45% of E added to the reaction). Importantly, surface chemistry modification via ligand exchange allowed conductive films of Ge1-xEx NCs to be prepared, which exhibit conductivities over large distances (25 MUm) relevant to optoelectronic device development of group IV NC thin films. PMID- 26281720 TI - Discovery and resupply of pharmacologically active plant-derived natural products: A review. AB - Medicinal plants have historically proven their value as a source of molecules with therapeutic potential, and nowadays still represent an important pool for the identification of novel drug leads. In the past decades, pharmaceutical industry focused mainly on libraries of synthetic compounds as drug discovery source. They are comparably easy to produce and resupply, and demonstrate good compatibility with established high throughput screening (HTS) platforms. However, at the same time there has been a declining trend in the number of new drugs reaching the market, raising renewed scientific interest in drug discovery from natural sources, despite of its known challenges. In this survey, a brief outline of historical development is provided together with a comprehensive overview of used approaches and recent developments relevant to plant-derived natural product drug discovery. Associated challenges and major strengths of natural product-based drug discovery are critically discussed. A snapshot of the advanced plant-derived natural products that are currently in actively recruiting clinical trials is also presented. Importantly, the transition of a natural compound from a "screening hit" through a "drug lead" to a "marketed drug" is associated with increasingly challenging demands for compound amount, which often cannot be met by re-isolation from the respective plant sources. In this regard, existing alternatives for resupply are also discussed, including different biotechnology approaches and total organic synthesis. While the intrinsic complexity of natural product-based drug discovery necessitates highly integrated interdisciplinary approaches, the reviewed scientific developments, recent technological advances, and research trends clearly indicate that natural products will be among the most important sources of new drugs also in the future. PMID- 26281734 TI - Atom-Cage Charge Transfer in Endohedral Metallofullerenes: Trapping Atoms Within a Sphere-Like Ridge of Avoided Crossings. AB - Endohedral fullerences have great potential for a variety of techological applications. Here we consider B@C60 and show that the amount of charge transfer from the semimetal boron atom to the cage is a strong function of the radial distance of the atom from the center of the fullerene, and it is controlled by multistate conical intersections whose associated ridge of avoided crossings has the topology of a Euclidean sphere. The potential energy surfaces of B@C60 are characterized by two kinds of local minima: those with a boron atom located in the geometric center of the fullerene, and those with a boron atom bound to the fullerene inner wall. At the lowest-energy minimum, at the center, the boron atom is neutral, whereas the transition to the wall is accompanied by an electron transfer from boron to the fullerene cage. The two kinds of minima are separated by a ridge of avoided crossings that forms a surface with a nearly spherical shape. The properties of such systems may be altered by controlling the populations of the two kinds of minima, for example, by application of an external field. Such switchable atom-cage charge transfer may find applications in novel molecular devices. PMID- 26281735 TI - A New Route to Nondestructive Top-Contacts for Molecular Electronics on Si: Pb Evaporated on Organic Monolayers. AB - Thermally evaporated Pb preserves the electronic properties of an organic monolayer (ML) on Si and surface passivation of the Si surface itself. The obtained current-voltage characteristics of Pb/ML/Si junctions agree with results obtained with the well-established Hg contact and preserve both the molecule induced dipole effect on, and length-attenuation of, the current. We rationalize our findings by the lack of interaction between the Pb and the Si substrate. This method is fast, scalable, and compatible with standard semiconductor processing, results in close to 100% yield, and can help the development of large-scale utilization of silicon-organic hybrid electronics. Our experimental data show a dependence of the transport across the molecules on the substrate orientation, expressed in the smaller distance decay parameter with Si(100) than that with Si(111). PMID- 26281737 TI - Observation of Optical Chemical Shift by Precision Nuclear Spin Optical Rotation Measurements and Calculations. AB - Nuclear spin optical rotation (NSOR) is a recently developed technique for detection of nuclear magnetic resonance via rotation of light polarization, instead of the usual long-range magnetic fields. NSOR signals depend on hyperfine interactions with virtual optical excitations, giving new information about the nuclear chemical environment. We use a multipass optical cell to perform the first precision measurements of NSOR signals for a range of organic liquids and find clear distinction between proton signals for different compounds, in agreement with our earlier theoretical predictions. Detailed first-principles quantum mechanical NSOR calculations are found to be in agreement with the measurements. PMID- 26281736 TI - Fragility of an Isochorically Confined Polymer Glass. AB - We report the effect of isochoric confinement on the dynamic fragility of a polymeric glass-former, that is, polystyrene (PS). Utilizing silica-capped PS nanospheres as a model system, the fictive temperature (Tf) and the isochoric heat capacity (Cv) are measured as a function of diameter via differential scanning calorimetry. By examining Tf as a function of cooling rate for each sample, the isochoric fragility (mv) is obtained, which decreases significantly as the diameter of the nanospheres is reduced from 260 to 129 nm. Hence, the temperature dependence of structural relaxation near the glass transition is weakened with isochoric confinement. PMID- 26281738 TI - Panchromatic "Dye-Doped" Polymer Solar Cells: From Femtosecond Energy Relays to Enhanced Photo-Response. AB - There has been phenomenal effort synthesizing new low-band gap polymer hole conductors which absorb into the near-infrared (NIR), leading to >10% efficient all-organic solar cells. However, organic light absorbers have relatively narrow bandwidths, making it challenging to obtain panchromatic absorption in a single organic semiconductor. Here, we demonstrate that (poly[2,6-(4,4-bis-(2 ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b0]dithiophene)-alt-4,7-(2,1,3-benzothiadia zole)] (PCPDTBT) can be "photo-sensitized" across the whole visible spectrum by "doping" with a visible absorbing dye, the (2,2,7,7-tetrakis(3-hexyl-5-(7-(4 hexylthiophen-2-yl)benzo[c][1,2,5]thiadiazol-4-yl)thiophen-2-yl)-9,9 spirobifluorene) (spiro-TBT). Through a comprehensive sub-12 femtosecond nanosecond spectroscopic study, we demonstrate that extremely efficient and fast energy transfer occurs from the photoexcited spiro-TBT to the PCPDTBT, and ultrafast charge injection happens when the system is interfaced with ZnO as a prototypal electron-acceptor compound. The visible photosensitization can be effectively exploited and gives panchromatic photoresponse in prototype polymer/oxide bilayer photovoltaic diodes. This concept can be successfully adopted for tuning and optimizing the light absorption and photoresponse in a broad range of polymeric and hybrid solar cells. PMID- 26281739 TI - Vibrational Spectra of a Mechanosensitive Channel. AB - We report the simulated vibrational spectra of a mechanosensitive membrane channel in different gating states. Our results show that while linear absorption is insensitive to structural differences, linear dichroism and sum-frequency generation spectroscopies are sensitive to the orientation of the transmembrane helices, which is changing during the opening process. Linear dichroism cannot distinguish an intermediate structure from the closed structure, but sum frequency generation can. In addition, we find that two-dimensional infrared spectroscopy can be used to distinguish all three investigated gating states of the mechanosensitive membrane channel. PMID- 26281740 TI - Charge Transfer or J-Coupling? Assignment of an Unexpected Red-Shifted Absorption Band in a Naphthalenediimide-Based Metal-Organic Framework. AB - We investigate and assign a previously reported unexpected transition in the metal-organic framework Zn2(NDC)2(DPNI) (1; NDC = 2,6-naphthalenedicarboxylate, DPNI = dipyridyl-naphthalenediimide) that displays linear arrangements of naphthalenediimide ligands. Given the longitudinal transition dipole moment of the DPNI ligands, J-coupling seemed possible. Photophysical measurements revealed a broad, new transition in 1 between 400 and 500 nm. Comparison of the MOF absorption spectra with that of a charge transfer (CT) complex formed by manual grinding of DPNI and H2NDC led to the assignment of the new band in 1 as arising from an interligand CT. Constrained density functional theory utilizing a custom long-range-corrected hybrid functional was employed to determine which ligands were involved in the CT transition. On the basis of relative oscillator strengths, the interligand CT was assigned as principally arising from pi-stacked DPNI/NDC dimers rather than the alternative orthogonal pairs within the MOF. PMID- 26281741 TI - The Absolute Shielding Constants of Heavy Nuclei: Resolving the Enigma of the (119)Sn Absolute Shielding. AB - We demonstrate that the apparent disagreement between experimental determinations and four-component relativistic calculations of the absolute shielding constants of heavy nuclei is due to the breakdown of the commonly assumed relation between the electronic contribution to the nuclear spin-rotation constants and the paramagnetic contribution to the NMR shielding constants. We demonstrate that this breakdown has significant consequences for the absolute shielding constant of (119)Sn, leading to errors of about 1000 ppm. As a consequence, we expect that many absolute shielding constants of heavy nuclei will be in need of revision. PMID- 26281742 TI - Electron Spin Manipulation via Encaged Cluster: Differing Anion Radicals of Y2@C82-Cs, Y2C2@C82-Cs, and Sc2C2@C82-Cs. AB - Endohedral metallofullerene species with controllable electron spin have attracted increasing attention along with their potential application in quantum information processing. In this paper, we report the electron spin manipulation via encage cluster through comparative studies on the anion radicals of metallofullerene Y2@C82-Cs, Y2C2@C82-Cs, and Sc2C2@C82-Cs. Although these three radical species have the same parent fullerene cage, we found that the unpaired spin characteristics as well as metal-spin couplings of them can be greatly affected by endohedral clusters. Furthermore, based on theoretical calculations, it was revealed that the encaged clusters can affect the electronic population of pristine endohedral metallofullerenes and eventually manipulate the spin distribution of their corresponding anion radicals. Our findings are referential to the spin coherence in information processing due to the variable paramagnetism of these metallofullerene radicals. PMID- 26281743 TI - CO2 Preactivation in Photoinduced Reduction via Surface Functionalization of TiO2 Nanoparticles. AB - Salicylate and salicylic acid derivatives act as electron donors via charge transfer complexes when adsorbed on semiconducting surfaces. When photoexcited, charge is injected into the conduction band directly from their highest occupied molecular orbital (HOMO) without needing mediation by the lowest unoccupied molecular orbital (LUMO). In this study, we successfully induce the chemical participation of carbon dioxide in a charge transfer state using 3-aminosalicylic acid (3ASA). We determine the geometry of CO2 using a combination of ultraviolet visible spectroscopy (UV-vis), surface enhanced Raman scattering (SERS), (13)C NMR, and electron paramagnetic resonance (EPR). We find CO2 binds on Ti sites in a carbonate form and discern via EPR a surface Ti-centered radical in the vicinity of CO2, suggesting successful charge transfer from the sensitizer to the neighboring site of CO2. This study opens the possibility of analyzing the structural and electronic properties of the anchoring sites for CO2 on semiconducting surfaces and proposes a set of tools and experiments to do so. PMID- 26281744 TI - Nanoscopic Amyloid Pores Formed via Stepwise Protein Assembly. AB - Protein aggregation leading to various nanoscale assemblies is under scrutiny due to its implications in a broad range of human diseases. In the present study, we have used ovalbumin, a model non-inhibitory serpin, to elucidate the molecular events involved in amyloid assembly using a diverse array of spectroscopic and imaging tools such as fluorescence, laser Raman, circular dichroism spectroscopy, and atomic force microscopy (AFM). The AFM images revealed a progressive morphological transition from spherical oligomers to nanoscopic annular pores that further served as templates for higher-order supramolecular assembly into larger amyloid pores. Raman spectroscopic investigations illuminated in-depth molecular details into the secondary structural changes of the protein during amyloid assembly and pore formation. Additionally, Raman measurements indicated the presence of antiparallel beta-sheets in the amyloid core. Overall, our studies revealed that the protein conformational switch in the context of the oligomers triggers the hierarchical assembly into nanoscopic amyloid pores. Our results will have broad implications in the structural characterization of amyloid pores derived from a variety of disease-related proteins. PMID- 26281745 TI - Seven Conformers of Neutral Dopamine Revealed in the Gas Phase. AB - The rotational spectrum of neutral dopamine has been investigated for the first time using a combination of Fourier transform microwave spectroscopy with laser ablation. The parameters extracted from the analysis of the spectrum unequivocally identify the existence of seven conformers of dopamine. (14)N nuclear quadrupole coupling interactions have been used to determine the orientation of the amino group probing the existence of stabilizing N-H...pi interactions for all observed conformers. PMID- 26281746 TI - Optimizing Electromagnetic Hotspots in Plasmonic Bowtie Nanoantennae. AB - Sensitivity is a key factor in the improvement of nanoparticle-based biosensors. Bowtie nanoantennae have shown high sensitivity for both surface-enhanced Raman scattering (SERS)- and localized surface plasmon resonance (LSPR)-based biosensing. In this work, optical bowtie nanoantennae with varying geometries were simulated, fabricated, and characterized. We successfully fabricated sub-5 nm gaps between prisms. The gap between prisms, the prism size, and the radius of curvature of the prism corners were characterized for their effects on the optical and electromagnetic properties. Bowties were characterized using LSPR, SERS, and photochemical near-field imaging. The results indicate that the radius of curvature of the prism corners has an important effect on the SERS abilities of a nanoparticle array. The trends described herein can be utilized to intelligently design highly sensitive SERS and LSPR biosensing substrates. PMID- 26281747 TI - Polarization Properties of Semiconductor Nanorod Heterostructures: From Single Particles to the Ensemble. AB - Semiconductor heterostructured seeded nanorods exhibit intense polarized emission, and the degree of polarization is determined by their morphology and dimensions. Combined optical and atomic force microscopy were utilized to directly correlate the emission polarization and the orientation of single seeded nanorods. For both the CdSe/CdS sphere-in-rod (S@R) and rod-in-rod (R@R), the emission was found to be polarized along the nanorod's main axis. Statistical analysis for hundreds of single nanorods shows higher degree of polarization, p, for R@R (p = 0.83), in comparison to S@R (p = 0.75). These results are in good agreement with the values inferred by ensemble photoselection anisotropy measurements in solution, establishing its validity for nanorod samples. On this basis, photoselection photoluminescence excitation anisotropy measurements were carried out providing unique information concerning the symmetry of higher excitonic transitions and allowing for a better distinction between the dielectric and the quantum-mechanical contributions to polarization in nanorods. PMID- 26281748 TI - On the Impact of Solvation on a Au/TiO2 Nanocatalyst in Contact with Water. AB - Water, the ubiquitous solvent, is also prominent in forming liquid-solid interfaces with catalytically active surfaces, in particular, with promoted oxides. We study the complex interface of a gold nanocatalyst, pinned by an F center on titania support, and water. The ab initio simulations uncover the microscopic details of solvent-induced charge rearrangements at the metal particle. Water is found to stabilize charge states differently from the gas phase as a result of structure-specific charge transfer from/to the solvent, thus altering surface reactivity. The metal cluster is shown to feature both "cationic" and "anionic" solvation, depending on fluctuation and polarization effects in the liquid, which creates novel active sites. These observations open up an avenue toward "solvent engineering" in liquid-phase heterogeneous catalysis. PMID- 26281749 TI - Molecular Design of Porphyrins for Dye-Sensitized Solar Cells: A DFT/TDDFT Study. AB - To design efficient sensitizers for dye-sensitized solar cells (DSSCs), a series of porphyrin sensitizers with different electron-donating and withdrawing substituents are investigated using the density functional theory (DFT) and time dependent DFT approach. We found that the designed dyes have smaller highest occupied molecular orbital to lowest unoccupied molecular orbital (HOMO-LUMO) energy gap values, and the absorption bands are broadened and shifted to longer wavelengths compared to the so far best sensitizer (YD2-o-C8). Importantly, our designed dyes have larger contributions of the anchoring group to the LUMOs, which enhance the electron injection process. Our calculation results indicated that the new systems should have better performance than the existing efficient dyes due to their improved optical properties. PMID- 26281750 TI - Observation of the Bending Mode of Interfacial Water at Silica Surfaces by Near Infrared Vibrational Sum-Frequency Generation Spectroscopy of the [Stretch + Bend] Combination Bands. AB - Vibrational sum-frequency generation (SFG) spectroscopy of interfacial water at mineral/aqueous interfaces is extended to the near-IR range containing the low cross section stretch + bend combination bands (nucomb = nuOH + deltaHOH) of liquid water at silica surfaces near 5000-5300 cm(-1), for the first time. The assignments of SFG spectra are supported by FTIR and Raman spectroscopic measurements of the bulk water nucomb modes. The SFG spectra contain significant contributions from two combinations, [nus + delta] ~ 5060 cm(-1) and [nuas + delta] ~ 5300 cm(-1). These measurements provide the first, to our knowledge, reported probe of the bending mode of water at buried interfaces. The data suggest that the interfacial water bending mode is blue-shifted from that of bulk water. PMID- 26281751 TI - Chemistry of NOx on TiO2 Surfaces Studied by Ambient Pressure XPS: Products, Effect of UV Irradiation, Water, and Coadsorbed K(.). AB - Self-cleaning surfaces containing TiO2 nanoparticles have been postulated to efficiently remove NOx from the atmosphere. However, UV irradiation of NOx adsorbed on TiO2 also was shown to form harmful gas-phase byproducts such as HONO and N2O that may limit their depolluting potential. Ambient pressure XPS was used to study surface and gas-phase species formed during adsorption of NO2 on TiO2 and subsequent UV irradiation at lambda = 365 nm. It is shown here that NO3(-), adsorbed on TiO2 as a byproduct of NO2 disproportionation, was quantitatively converted to surface NO2 and other reduced nitrogenated species under UV irradiation in the absence of moisture. When water vapor was present, a faster NO3(-) conversion occurred, leading to a net loss of surface-bound nitrogenated species. Strongly adsorbed NO3(-) in the vicinity of coadsorbed K(+) cations was stable under UV light, leading to an efficient capture of nitrogenated compounds. PMID- 26281752 TI - Theoretical Design of Molecular Electrocatalysts with Flexible Pendant Amines for Hydrogen Production and Oxidation. AB - The design of hydrogen oxidation and production electrocatalysts is important for the development of alternative renewable energy sources. The overall objective is to maximize the turnover frequency and minimize the overpotential. We use computational methods to examine a variety of nickel-based molecular electrocatalysts with pendant amines. Our studies focus on the proton-coupled electron transfer (PCET) process involving electron transfer between the complex and the electrode and intramolecular proton transfer between the nickel center and the nitrogen of the pendant amine. The concerted PCET mechanism, which tends to require a lower overpotential, is favored by a smaller equilibrium Ni-N distance and a more flexible pendant amine ligand, thereby decreasing the energetic penalty for the nitrogen to approach the nickel center for proton transfer. Our calculations provide predictions about designing catalysts that incorporate these properties. These design principles will be useful for developing the next generation of hydrogen catalysts. PMID- 26281753 TI - A Novel Mechanism for Nitric Oxide Production in Nitroalkyl Radicals that Circumvents Nitro-Nitrite Isomerization. AB - In this study, we present a novel mechanism for NO loss from nitroalkyl radicals that circumvents the traditional higher-energy nitro-nitrite isomerization. We characterize the intrinsic reaction coordinate at the B3LYP/6-311++g(3df,2p) level of theory and calculate the transition-state energies using the G4 composite method; the subsequent dynamics en route to the highly exothermic NO + acetone product channel proceeds through a three-membered ring intermediate. Crossed laser-molecular beam scattering experiments on the 2-nitro-2-propyl radical confirm the importance of this new mechanism in determining the product branching. PMID- 26281754 TI - Lithium Economy: Will It Get the Electric Traction? PMID- 26281755 TI - Gadd45b Mediates Electroconvulsive Shock Induced Proliferation of Hippocampal Neural Stem Cells. AB - BACKGROUND: Electroconvulsive shock (ECS), also known as an electroconvulsive therapy (ECT), is an effective and safe treatment for neuropsychiatric disorders including pharmacoresistant major depressive disorder. Previous research in animal models suggests ECS efficacy is achieved by Gadd45b-mediated increases in adult hippocampal neurogenesis. OBJECTIVE/HYPOTHESIS: The present study aims to delineate the role of Gadd45b in mediating proliferation of neural stem cell types including quiescent radial glia-like (RGL) and amplifying non-radial glia like (non-RGL) neural precursors following ECS. METHODS: RGL and non-RGL neural stem cell populations defined by co-localization of MCM2+ and nestin+ cells and morphologically by the presence of radial processes were stereologically analyzed. RESULTS: ECS increased hippocampal density of both quiescent RGLs and amplifying non-RGLs. CONCLUSIONS: Gadd45b mediates the action of ECS-induced proliferation through activation of quiescent neural stem cells. PMID- 26281756 TI - Morphological and ultrastructural examination of senescence in Morchella elata. AB - In recent years, the artificial cultivation of Morchella mushrooms that belong to Elata Clade, including Morchella elata, has been developed rapidly in China. However, the prominent problem of spawn aging has been frustrating the morel farming. In this paper, aging in M. elata was achieved from 12 to 17 subcultures and lifespan of 1536-2256 h by successive subculturing. The lifespan can be roughly divided into juvenile phase and senescent phase with respect to the mycelia linear growth rate. After a certain period of rapid growth with almost constant rate at the juvenile phase, the isolate entered the senescent phase characterized by slow down of mycelia growth, producing pigments ahead of time and final death of the apical hyphae. The period of the senescent phase was definitely 240-288 h; while that of the juvenile phase was diverse relying on different isolates. Moreover, microscopic study showed that angles between the leading and primary hyphae increased constantly with aging. In senesced hyphal cells of M. elata, the typical characteristics of autophagy (enlargement of vacuoles and existence of organelles sequestrated lysosomes) and apoptosis (condensation of the cytoplasm and nuclear and plasmolysis) were observed. In addition, in the final stage of senescence, the apical hyphae collapsed with the plasma membrane and all the cellular organelles disrupted, indicated a necrotic mode of cell death. Taken together, these data revealed the involvement of autophagy, apoptosis and necrosis in senescence of M. elata. The characterization and molecular mechanism of autophagy, apoptosis and necrosis need further study and the systematic study of morel aging will be beneficial for the healthy development of morel farming. PMID- 26281757 TI - Isolation and characterization of endochitinase and exochitinase of Setaria cervi. AB - Chitin metabolism has been shown to have a role in the development of parasitic nematodes including filarial parasites and the enzymes associated with chitin metabolism have been considered as potential vaccine and drug target. Chitinases are members of the enzyme superfamily of glycoside hydrolases, which are characterized by the ability to hydrolyze glycosidic bonds in chitin chain by either an endolytic or an exolytic mechanism. In the present study, we have demonstrated the chitinase (exochitinase and endochitinase) activity in different stages of Setaria cervi (bovine filarial parasite) and have also purified and characterized the endochitinase from microfilarial stage of the parasite. The chitinase activity has been detected in adult and microfilarial stages of S. cervi using the fluorescent substrates. The S. cervi adult stage was found to have high activity of exochitinase (28.72+/-0.25 nmol/min/mg) while microfilarial stage showed high activity of endochitinase (24.40+/-0.25 nmol/min/mg). Native polyacrylamide gel electrophoresis, followed by staining of enzyme activity with fluorescent substrates, revealed single isoenzymic form of exochitinase in adults and endochitinase in microfilariae of S. cervi. The endochitinase from S. cervi microfilariae was purified employing chitin affinity matrix and DEAE-Sephacel ion exchange chromatography. The enzyme was purified about 55 fold with an enzyme recovery of 22.33%. The purified enzyme exhibited a doublet of protein bands on SDS-PAGE at 65-70 kDa. The closantel (chitinase inhibitor) strongly inhibited the enzyme activity of S. cervi microfilariae endochitinase with a Ki value of 4.3+/ 0.18 MUM. PMID- 26281758 TI - Quality of life impact related to foot health in a sample of sea workers. AB - BACKGROUND: People working at sea show a marked presence of musculoskeletal pain as well as an important coexistence of pain in diverse anatomical regions, which is believed to have a harmful effect on the quality of life related to foot health. The aim is to describe and compare the impact in a sample of sea workers and people who work on the ground in the light of the scores obtained with regard foot health and health in general. METHODS: A sample of 94 participants of a mean age of 41.29 +/- 10.603 came to a health centre where self-reported data were registered, informants' professional activity was determined and the scores obtained were compared in the Foot Health Status Questionnaire. RESULTS: The sea workers group showed a worse quality of life related to health in general and to foot health specifically. Differences between the two groups were evaluated by means of a t-test for independent samples, showing statistical significance (P < 0.05) for the dimensions of pain and general health related to the foot. CONCLUSIONS: People working at sea present a negative impact on the quality of life related to foot health, which appears to be associated with the presence of deformities, sprains, plantar warts and fungus. PMID- 26281759 TI - Head west or left, east or right: interactions between memory systems in neurocognitive aging. AB - Cognitive aging is accompanied by decline in multiple domains of memory. Here, we developed a T-maze task that required rats to learn competing hippocampal, and striatal navigation strategies in succession, across days. A final session increased demands on cognitive flexibility and required within-day switching between strategies, emphasizing capacities that engage the prefrontal cortex. Background characterization in young and aged rats used a water maze protocol optimized for individual differences in hippocampal integrity. Consistent with earlier work, young adults acquired place strategies in the T-maze faster than response, whereas the opposite was observed in aged rats with impaired spatial memory. The novel result was that aged animals with preserved spatial memory displayed a qualitatively distinct pattern, acquiring place and response strategies equally rapidly, without disruption when switching between them. Subsequent in situ hybridization for the plasticity-related immediate-early gene Arc revealed that while increasing demands on cognitive flexibility and within day strategy switching potently engaged the prefrontal cortex in young adult and aged-impaired rats, Arc expression was insensitive in aged rats with normal spatial memory and superior switching abilities. Together, the results indicate that cognitive aging is an emergent property of the interactions between memory systems, and that successful cognitive outcomes reflect a distinct neuroadaptive process rather than a slower rate of aging. PMID- 26281761 TI - Comparison of global inventories of CO2 emissions from biomass burning during 2002-2011 derived from multiple satellite products. AB - This study compared five widely used globally gridded biomass burning emissions inventories for the 2002-2011 period (Global Fire Emissions Database 3 (GFED3), Global Fire Emissions Database 4 (GFED4), Global Fire Assimilation System 1.0 (GFAS1.0), Fire INventory from NCAR 1.0 (FINN1.0) and Global Inventory for Chemistry-Climate studies-GFED4 (G-G)). Average annual CO2 emissions range from 6521.3 to 9661.5 Tg year(-1) for five inventories, with extensive amounts in Africa, South America and Southeast Asia. Coefficient of Variation for Southern America, Northern and Southern Africa are 30%, 39% and 48%. Globally, the majority of CO2 emissions are released from savanna burnings, followed by forest and cropland burnings. The largest differences among the five inventories are mainly attributable to the overestimation of CO2 emissions by FINN1.0 in Southeast Asia savanna and cropland burning, and underestimation in Southern Africa savanna and Amazon forest burning. The overestimation in Africa by G-G also contributes to the differences. PMID- 26281760 TI - The role of conduct disorder in the relationship between alcohol, nicotine and cannabis use disorders. AB - BACKGROUND: Genetic influences contribute significantly to co-morbidity between conduct disorder and substance use disorders. Estimating the extent of overlap can assist in the development of phenotypes for genomic analyses. METHOD: Multivariate quantitative genetic analyses were conducted using data from 9577 individuals, including 3982 complete twin pairs and 1613 individuals whose co twin was not interviewed (aged 24-37 years) from two Australian twin samples. Analyses examined the genetic correlation between alcohol dependence, nicotine dependence and cannabis abuse/dependence and the extent to which the correlations were attributable to genetic influences shared with conduct disorder. RESULTS: Additive genetic (a(2) = 0.48-0.65) and non-shared environmental factors explained variance in substance use disorders. Familial effects on conduct disorder were due to additive genetic (a(2) = 0.39) and shared environmental (c(2) = 0.15) factors. All substance use disorders were influenced by shared genetic factors (rg = 0.38-0.56), with all genetic overlap between substances attributable to genetic influences shared with conduct disorder. Genes influencing individual substance use disorders were also significant, explaining 40-73% of the genetic variance per substance. CONCLUSIONS: Among substance users in this sample, the well-documented clinical co-morbidity between conduct disorder and substance use disorders is primarily attributable to shared genetic liability. Interventions targeted at generally reducing deviant behaviors may address the risk posed by this shared genetic liability. However, there is also evidence for genetic and environmental influences specific to each substance. The identification of these substance-specific risk factors (as well as potential protective factors) is critical to the future development of targeted treatment protocols. PMID- 26281762 TI - Effect of biochar aging on surface characteristics and adsorption behavior of dialkyl phthalates. AB - The implications of biochar aging regarding their material properties as well as their interactions with other contaminants are not vivid. We report the role of biochar aging on sorption behavior of di-alkyl phthalates (PAEs). Biochars used in this study were produced from peanut-shell and their aging was simulated by chemical oxidation. The structural composition and morphology of the obtained biochars, before and after oxidation with HNO3/H2SO4, were analyzed by element composition, XPS, DRIFT, and SEM/EDX. Several experimental results unequivocally showed oxygen enrichment in the mixed acid treated samples compared to their precursors. Despite surface area reduction and pore destruction, increased PAEs sorption on oxidized biochar surfaces portrayed existence of strong PAEs binding sites. The adsorption of PAEs on oxidized biochar surface is a cumulative influence of hydrophobic interactions and pi-pi electron donor-acceptor interactions. Our results suggest that imminent aging of biochar upon environmental exposure may change their sorbent properties. PMID- 26281763 TI - Methylated derivatives of myricetin enhance life span in Caenorhabditis elegans dependent on the transcription factor DAF-16. AB - Only certain flavonoids have been shown to enhance life span. This was pointed out for e.g. myricetin in the nematode Caenorhabditis elegans. However, the structural requirements responsible for this effect are not known. We used methylated derivatives of myricetin (laricitrin, syringetin, myricetintrimethylether) to investigate if free OH moieties in the B-ring are necessary for the life span extending effect. In analogy to myricetin, all derivatives increased the life span, decreased oxidative stress (DCF) and decreased the accumulation of lipofuscin. In contrast to myricetin, the methylated compounds strongly enhanced the resistance against thermal stress. Furthermore, treatment with the derivatives induced a much stronger nuclear localization of the DAF-16 transcription factor (FoxO homologue). Additionally, no antioxidant effects and only minor effects on life span prolongation and stress resistance were detectable for the methylated compounds in a DAF-16 deficient nematode strain. Comparable to the dietary flavonoid myricetin, the methylated myricetin derivatives laricitrin, syringetin and myricetintrimethylether strongly enhance the life span of C. elegans. Therefore, OH groups of ring B are not necessary for this effect. Only the methylated compounds increase the stress resistance of the nematode which was dependent on DAF-16. These findings suggest that methylation of myricetin increases the biofunctionality. PMID- 26281764 TI - J.B.S. Haldane as I knew him, with a brief account of his contribution to mutation research. AB - J.B.S. Haldane made important contributions to several sciences although he did not possess an academic qualification in any branch of science. A classical scholar, who grew up in a scientific household in Oxford, Haldane was taught the principles of scientific experimentation from his childhood by his father, the distinguished physiologist John Scott Haldane. Collaborating with his father, Haldane contributed to respiratory physiology but soon switched to genetics, especially population genetics. He investigated mathematically the dynamics of selection - mutation balance in populations - concluding that it is mutation that determines the course of evolution. Besides genetics, Haldane was noted for his important contributions to enzyme kinetics, origin of life, biometry, cybernetics, cosmology and deep sea diving, among others. PMID- 26281765 TI - Engineered mutations in fibrillin-1 leading to Marfan syndrome act at the protein, cellular and organismal levels. AB - Fibrillins are the major components of microfibrils in the extracellular matrix of elastic and non-elastic tissues. They are multi-domain proteins, containing primarily calcium binding epidermal growth factor-like (cbEGF) domains and 8 cysteine/transforming growth factor-beta binding protein-like (TB) domains. Mutations in the fibrillin-1 gene give rise to Marfan syndrome, a connective tissue disorder with clinical complications in the cardiovascular, skeletal, ocular and other organ systems. Here, we review the consequences of engineered Marfan syndrome mutations in fibrillin-1 at the protein, cellular and organismal levels. Representative point mutations associated with Marfan syndrome in affected individuals have been introduced and analyzed in recombinant fibrillin-1 fragments. Those mutations affect fibrillin-1 on a structural and functional level. Mutations which impair folding of cbEGF domains can affect protein trafficking. Protein folding disrupted by some mutations can lead to defective secretion in mutant fibrillin-1 fragments, whereas fragments with other Marfan mutations are secreted normally. Many Marfan mutations render fibrillin-1 more susceptible to proteolysis. There is also evidence that some mutations affect heparin binding. Few mutations have been further analyzed in mouse models. An extensively studied mouse model of Marfan syndrome expresses mouse fibrillin-1 with a missense mutation (p.C1039G). The mice display similar characteristics to human patients with Marfan syndrome. Overall, the analyses of engineered mutations leading to Marfan syndrome provide important insights into the pathogenic molecular mechanisms exerted by mutated fibrillin-1. PMID- 26281767 TI - Conditional mutations in Drosophila melanogaster: On the occasion of the 150th anniversary of G. Mendel's report in Brunn. AB - The basis for modern genetics was laid by Gregor Mendel. He proposed that traits belonging to the intraspecific variability class be studied. However, individuals of one species possess traits of another class. They are related to intraspecific similarity. Individuals never differ from each other in these traits. By analogy with traits varying within a species and determined by genes, it is conjectured that intraspecific similarity is determined by genes, too. If so, mutations in these genes can be obtained. This paper provides a review of works published in 2000-2014 that: (1) propose breeding methods for detection of mutations in Drosophila melanogaster genes that lead intraspecific similarity; these mutations were called conditional; (2) describe collections of conditional mutations in chromosomes X, 2, and 3 of Drosophila; (3) show unusual features of epigenetic nature in the mutants; and (4) analyze these features of the mutants. Based on the peculiarities of manifestation it is supposed that the recognized conditional mutations occur in genes responsible for intraspecific similarity. The genes presumably belong to the so-called regulatory network of the Drosophila genome. This approach expands the scope of breeding analysis introduced by G. Mendel for heredity studies 150 years ago. PMID- 26281768 TI - Theoretical considerations for thresholds in chemical carcinogenesis. AB - There is increasing evidence for non-linear relationships for gene mutations, chromosomal aberrations and even tumor incidences in response to low doses of genotoxic carcinogens. To attain the biological relevance of such non-linear responses, there is a need to identify the underlying defense mechanisms that allow tolerance to low doses of genotoxicants. This communication discusses presumptive cancer prevention mechanisms that may contribute to thresholds, i.e. points of departure, for each endpoint, from initial DNA lesion to tumor formation. We discuss a sequential order of genome protection during carcinogenesis where genotoxicant scavenging, cellular efflux, DNA repair, elimination of damaged cells by apoptosis, autophagy, silencing by DNA damage triggered replicative senescence, and finally, elimination of transformed (premalignant) cells by the immune system are thought to be responsible for a threshold in tumor formation. We highlight DNA repair, for which experimental evidence has been recently provided to dictate a role in PoDs. In conclusion, from a theoretical perspective it is reasonable to posit that tolerance to low dose levels exists for each requisite step of tumor formation and these tolerance mechanisms are critical in determining thresholds in chemical carcinogenesis. PMID- 26281769 TI - Supramolecular fluorescence enhancement via coordination-driven self-assembly in bis-picolylcalixarene blue-emitting M2L2Xn macrocycles. AB - The lower-rim functionalised distal bis-(4-picolyl)-p-tert-butylcalix[4]arene () selectively and quantitatively self-assembles into a series of discrete [2 + 2] blue-emitting metallacycles of general formula M2L2Xn with diverse metal salts (M = Zn(2+), Pd(2+), Ag(+), and Cd(2+); X = Cl(-), NO3(-), ClO4(-), BF4(-) , CF3SO3( ), PF6(-), SbF6(-); n = 2, 4). Macrocycle assembly has been corroborated by 2D DOSY NMR and ESI-MS analyses, which further indicate that the M2L2Xn entities are quite stable and persist as robust and discrete macrocyclic species in solution. While free units display modest blue emission (lambdamax = 307-405 nm), self assembly of M2L2Xn results in amplified fluorescence (up to 13-fold). This remarkable enhancement may be primarily ascribed to the increase in conformational rigidity imposed on the units by supramolecular assembly formation upon metal coordination to the pyridyl groups; in addition, subtle intensity emission modulation may be provided by the different metal components. Titrations aimed at exploring the possibilities for ratiometric detection of metal cations or sensing of nitroaromatic species, revealed that the M2L2Xn platform may be a suitable "turn-on/off" system. Our results provide valuable insights into luminescence enhancement within the context of coordination-driven assemblies, which may be engineered to increase their fluorescence by imposing rigidity on the chromophores. PMID- 26281770 TI - Treatment with the combination of ibandronate plus eldecalcitol has a synergistic effect on inhibition of bone resorption without suppressing bone formation in ovariectomized rats. AB - Bisphosphonates are widely used in the treatment of osteoporosis and contribute to the reduction of bone fractures. Ibandronate (IBN) is a highly potent, nitrogen-containing bisphosphonate, which is administered orally or intravenously at extended dosing intervals. Vitamin D or active vitamin D3 derivatives are also used in the treatment of osteoporosis, and are often used in combination with other drugs. In this study, we investigated the effect of treatment with the combination of once-monthly s.c. dosing of IBN plus once-daily oral eldecalcitol (ELD), an active vitamin D3 derivative, using aged ovariectomized (OVX) rats. Treatment was started the day after OVX, and analyses were performed 4, 8, and 12 weeks thereafter by determination of bone markers, bone mineral density, biomechanical properties, and histomorphometry. The combination treatment showed a synergistic effect in increasing both lumbar and femoral BMD, and resulted in a significant increase in bone ultimate load. The combination of IBN plus ELD acted synergistically to reduce bone resorption, whereas bone formation did not decrease any more than with monotherapy with either IBN or ELD. Bone formation independent of bone resorption (a process known as 'minimodeling') was not changed in vehicle treated OVX rats despite the increase in bone turnover. ELD upregulated minimodeling, which was however not diminished in the combination treatment. In conclusion, treatment with the combination of IBN plus ELD was beneficial in the treatment of osteoporosis in aged OVX rats. It exhibited a synergistic inhibitory effect on bone resorption and keeps bone formation at the level of sham controls. This uncoupling of bone resorption/bone formation was affected, to some extent, by minimodeling-based bone formation which is independent of bone resorption. This combination regimen which showed synergistic effect on BMD and bone ultimate load without inhibition of bone formation may be beneficial in long-term osteoporosis treatment to prevent bone fractures. PMID- 26281766 TI - Response of transposable elements to environmental stressors. AB - Transposable elements (TEs) comprise a group of repetitive sequences that bring positive, negative, as well as neutral effects to the host organism. Earlier considered as "junk DNA," TEs are now well-accepted driving forces of evolution and critical regulators of the expression of genetic information. Their activity is regulated by epigenetic mechanisms, including methylation of DNA and histone modifications. The loss of epigenetic control over TEs, exhibited as loss of DNA methylation and decondensation of the chromatin structure, may result in TEs reactivation, initiation of their insertional mutagenesis (retrotransposition) and has been reported in numerous human diseases, including cancer. Accumulating evidence suggests that these alterations are not the simple consequences of the disease, but often may drive the pathogenesis, as they can be detected early during disease development. Knowledge derived from the in vitro, in vivo, and epidemiological studies, clearly demonstrates that exposure to ubiquitous environmental stressors, many of which are carcinogens or suspected carcinogens, are capable of causing alterations in methylation and expression of TEs and initiate retrotransposition events. Evidence summarized in this review suggests that TEs are the sensitive endpoints for detection of effects caused by such environmental stressors, as ionizing radiation (terrestrial, space, and UV radiation), air pollution (including particulate matter [PM]-derived and gaseous), persistent organic pollutants, and metals. Furthermore, the significance of these effects is characterized by their early appearance, persistence and presence in both, target organs and peripheral blood. Altogether, these findings suggest that TEs may potentially be introduced into safety and risk assessment and serve as biomarkers of exposure to environmental stressors. Furthermore, TEs also show significant potential to become invaluable surrogate biomarkers in clinic and possible targets for therapeutic modalities for disease treatment and prevention. PMID- 26281771 TI - Analysis of 17 neurotransmitters, metabolites and precursors in zebrafish through the life cycle using ultrahigh performance liquid chromatography-tandem mass spectrometry. AB - An ultrahigh performance liquid chromatography-tandem mass spectrometry method for the identification and quantification of neurotransmitters, metabolites and precursors at different stages in zebrafish life was developed. Betaine, glutamine, glutamic acid, gamma-aminobutyric acid, phosphocholine, glycerophosphocholine, cytidine 5'-diphosphocholine, choline, acetylcholine, dopamine, norepinephrine, serotonin, tyrosine, epinephrine, tryptophan, 5 hydroxyindolacetic acid and agmatine were selected as analytes. The method consisted of a simple deproteinization of samples using methanol and formic acid, subsequent injection onto the chromatographic equipment and quantification with a triple quadrupole mass spectrometer detector using an electrospray ionization interface in positive mode. Limits of detection ranged from 0.02 to 11ngmL(-1) and limits of quantification from 0.1 to 38ngmL(-1), depending on the analyte. The method was validated according to US Food and Drugs Administration (FDA) guideline for bioanalytical assays. Precision, expressed as relative standard deviation (%RSD), was lower than 15% in all cases, and the determination coefficient (R(2)) was equal or higher than 99.0% with a residual deviation for each calibration point lower than +/-25%. Mean recoveries were between 85% and 115%. The method was applied to determine of these compounds in zebrafish from early stages of development to adulthood and showed the time-course of neurotransmitters and others neurocompounds through the life cycle. The possibility of measuring up to 17 compounds related with the main neurotransmitter systems in a simple analytical method will complement and reinforce the use of zebrafish in multiple applications in the field of neurosciences. The proposed method will facilitate future studies related with brain development. PMID- 26281773 TI - Liquid chromatography/tandem mass spectrometry method for simultaneous quantification of eight endogenous nucleotides and the intracellular gemcitabine metabolite dFdCTP in human peripheral blood mononuclear cells. AB - Quantification of endogenous nucleotides is of interest for investigation of numerous cellular biochemical processes, such as energy metabolism and signal transduction, and may also be applied in cancer and antiretroviral therapies in which nucleoside analogues are used. For these purposes we developed and validated a sensitive and high accuracy ion-pair liquid chromatography tandem mass spectrometry (IP LC-MS/MS) method for simultaneous quantification of eight endogenous nucleotides (ATP, CTP, GTP, UTP, dATP, dCTP, dGTP, dTTP) and 2',2' difluoro-2'-deoxycytidine triphosphate (dFdCTP), an intracellular metabolite of the nucleoside analogue gemcitabine. The assay was validated using 200MUL aliquots of peripheral blood mononuclear cell (20*10(6)cells/ml, 4*10(6)cells) extracts, pretreated with activated charcoal and spiked with unlabeled nucleotides, deoxynucleotides and dFdCTP. Analytes were extracted by simple precipitation with cold 60% methanol containing isotope labeled internal standards and separated on a porous graphitic carbon column. For method validation, the concentration ranges were: 0.125-20.8pmol injected for deoxynucleotides, 0.25-312.5pmol injected for dFdCTP and 5-3200pmol injected for nucleotides. The highest coefficients of variation (CV) were 12.1% for within run assay and 11.4% for between run assay, both representing the precision at the lowest analyte concentrations. The method was applied to monitor dFdCTP and changes in endogenous nucleotides in patients who were receiving gemcitabine infusions. PMID- 26281772 TI - Quantitation of celecoxib and four of its metabolites in rat blood by UPLC-MS/MS clarifies their blood distribution patterns and provides more accurate pharmacokinetics profiles. AB - A sensitive UPLC-MS/MS method was established and validated for the quantitation of celecoxib and its metabolites in rat blood. The analytes were extracted from rat blood samples by a salting-out liquid-liquid extraction method followed by the UPLC chromatography. The mass analysis of effluent was performed on an API 5500 Qtrap mass spectrometer via multiple reactions monitoring (MRM). The linear response ranges were 0.3-20000nM for celecoxib, and 1.2-20000nM, 0.3-20000nM, 2.0 2000nM, 1.5-6000nM for its metabolites carboxycelecoxib (M2), hydroxycelecoxib (M3), hydroxycelecoxib glucuronide (M1), and carboxycelecoxib glucuronide (M5), respectively. The inter-day and intra-day accuracies were within 85-115%, and the inter-day and intra-day precision were acceptable (<12%) for all analytes. Recoveries were above 70% and no obvious matrix effects were observed. The validated UPLC-MS/MS method was successfully applied to a pharmacokinetics study of oral celecoxib (20mg/kg) in Sprague-Dawley rats, and the rat blood concentrations (0-48h) of celecoxib and two of its metabolites M2 and M3 were successfully determined. Using the same method, we also showed preferential distributions of celecoxib, M2 and M3 in the blood cells as compared to the plasma. In conclusion, our results showed that our validated LC-MS/MS method can be successfully used for the pharmacokinetic studies of celecoxib and that the blood cells are a very important compartment for this drug such that profiles of celecoxib and its metabolites in whole blood will be more comprehensive and accurate representation of their profiles in vivo than the plasma. PMID- 26281774 TI - Increase of chromium tolerance in Scenedesmus acutus after sulfur starvation: Chromium uptake and compartmentalization in two strains with different sensitivities to Cr(VI). AB - In photosynthetic organisms sulfate constitutes the main sulfur source for the biosynthesis of GSH and its precursor Cys. Hence, sulfur availability can modulate the capacity to cope with environmental stresses, a phenomenon known as SIR/SED (Sulfur Induced Resistance or Sulfur Enhanced Defence). Since chromate may compete for sulfate transport into the cells, in this study chromium accumulation and tolerance were investigated in relation to sulfur availability in two strains of the unicellular green alga Scenedesmus acutus with different Cr sensitivities. Paradoxically, sulfur deprivation has been demonstrated to induce a transient increase of Cr-tolerance in both strains. Sulfur deprivation is known to enhance the sulfate uptake/assimilation pathway leading to important consequences on Cr-tolerance: (i) reduced chromate uptake due to the induction of high affinity sulfate transporters (ii) higher production of cysteine and GSH which can play a role both through the formation of unsoluble complexes and their sequestration in inert compartments. To investigate the role of the above mentioned mechanisms, Cr accumulation in total cells and in different cell compartments (cell wall, membranes, soluble and miscellaneous fractions) was analyzed in both sulfur-starved and unstarved cells. Both strains mainly accumulated chromium in the soluble fraction, but the uptake was higher in the wild-type. In this type a short period of sulfur starvation before Cr(VI) treatment lowered chromium accumulation to the level observed in the unstarved Cr tolerant strain, in which Cr uptake seems instead less influenced by S starvation, since no significant decrease was observed. The increase in Cr tolerance following S-starvation seems thus to rely on different mechanisms in the two strains, suggesting the induction of a mechanism constitutively active in the Cr-tolerant strain, maybe a high affinity sulfate transporter also in the wild-type. Changes observed in the cell wall and membrane fractions suggest a strong involvement of these compartments in Cr-tolerance increase following S starvation. PMID- 26281775 TI - Is chemosensitisation by environmental pollutants ecotoxicologically relevant? AB - The active cellular efflux of toxicants is an efficient biological defense mode present in all organisms. By blocking this so-called multixenobiotic resistance transport-a process also referred to as chemosensitisation-, cellular bioaccumulation and the sensitivity of organisms towards environmental pollutants can increase. So far, a wide range of compounds, including pesticides, pharmaceuticals, fragrances, and surfactants, have been identified as chemosensitisers. Although, significant on a cellular level, the environmental impact of chemosensitisation on the organism level is not yet understood. Critically evaluating existing data, this paper identifies research needs to support our tentative conclusion that chemosensitisation may well enhance the risks of chemical exposure to aquatic organisms. Our conclusion is based on studies investigating the impact of individual chemicals and complex environmental mixtures on aquatic wildlife and a chemosensitiser mixture toxicity model which, however, is subject to great uncertainty due to substantial knowledge gaps. Those uncertainties include the inconsistent reporting of effect data, the lack of representative environmental contaminants tested for chemosensitisation, and the publishing of highly unreliable nominal exposure concentrations. In order to confirm the tentative conclusion of this paper, we require the significant and systematic investigation of a broader set of chemicals and environmental samples with a harmonised set of bioassays and rigorously controlled freely dissolved effect concentrations. PMID- 26281776 TI - Unilateral linear papulosquamous rash in a healthy young man. PMID- 26281777 TI - Towards destination therapy with left ventricular assist devices in Japan. PMID- 26281778 TI - Commentary: A Quest for a Novel Peripheral Biomarker for Narcolepsy. PMID- 26281779 TI - The puzzling character of repetitive DNA in Phodopus genomes (Cricetidae, Rodentia). AB - Three novel repetitive DNA sequences are described, presenting a similar heterochromatic chromosomal location in two hamster species: Phodopus roborovskii and Phodopus sungorus (Cricetidae, Rodentia). Namely, two species-specific repetitive sequences (PROsat from P. roborovskii and PSUchr1sat from P. sungorus) surrounding a third one (PsatDNA), that is shared by both hamster genomes. Fiber FISH analyses revealed that PROsat intermingles with PsatDNA in P. roborovskii and PSUchr1sat intermingles with PsatDNA in P. sungorus. A model explaining the evolution of this intricate chromosomal distribution is proposed, which can explain better the evolution of these very derivative genomes (in comparison to the ancestral Muroidea). The most plausible evolutionary scenario seems to be the expansion of a number of repeats into other's domain, most probably resulting in its intermingling, followed by the subsequent spread of these complex repeats from a single chromosomal location to other chromosomes. Evidences of an association between repetitive sequences and the chromosome evolution process were observed, namely for PROsat. Most probably, the evolutionary breakpoints that shaped PRO and PSU chromosomes (pericentric inversions and fusions) occurred within the boundaries of PROsat blocks in the ancestor. The repeats high diversity at the heterochromatic regions of Phodopus chromosomes, together with its complex organization, suggests that these species are important models for evolutionary studies, namely in the investigation of a possible relationship between repetitive sequences and the occurrence of chromosomal rearrangements and consequently, in genome evolution. PMID- 26281780 TI - Epigenetics: Chromatin reorganization on a 'mega' scale. PMID- 26281784 TI - The dynamics of mitochondrial DNA heteroplasmy: implications for human health and disease. AB - Common genetic variants of mitochondrial DNA (mtDNA) increase the risk of developing several of the major health issues facing the western world, including neurodegenerative diseases. In this Review, we consider how these mtDNA variants arose and how they spread from their origin on one single molecule in a single cell to be present at high levels throughout a specific organ and, ultimately, to contribute to the population risk of common age-related disorders. mtDNA persists in all aerobic eukaryotes, despite a high substitution rate, clonal propagation and little evidence of recombination. Recent studies have found that de novo mtDNA mutations are suppressed in the female germ line; despite this, mtDNA heteroplasmy is remarkably common. The demonstration of a mammalian mtDNA genetic bottleneck explains how new germline variants can increase to high levels within a generation, and the ultimate fixation of less-severe mutations that escape germline selection explains how they can contribute to the risk of late-onset disorders. PMID- 26281785 TI - Knocking down disease: a progress report on siRNA therapeutics. AB - Small interfering RNAs (siRNAs), which downregulate gene expression guided by sequence complementarity, can be used therapeutically to block the synthesis of disease-causing proteins. The main obstacle to siRNA drugs - their delivery into the target cell cytosol - has been overcome to allow suppression of liver gene expression. Here, we review the results of recent clinical trials of siRNA therapeutics, which show efficient and durable gene knockdown in the liver, with signs of promising clinical outcomes and little toxicity. We also discuss the barriers to more widespread applications that target tissues besides the liver and the most promising avenues to overcome them. PMID- 26281786 TI - S argassum muticum-synthesized silver nanoparticles: an effective control tool against mosquito vectors and bacterial pathogens. AB - Mosquito-borne diseases represent a deadly threat for millions of people worldwide. Furthermore, pathogens and parasites polluting water also constitute a severe plague for populations of developing countries. In this research, silver nanoparticles (AgNP) were synthesized using the aqueous extract of the seaweed Sargassum muticum. The production of AgNP was confirmed by surface plasmon resonance band illustrated in UV-vis spectrophotometry. AgNP were characterized by FTIR, SEM, EDX, and XRD analyses. AgNP were mostly spherical in shape, crystalline in nature, with face-centered cubic geometry, and mean size was 43-79 nm. Toxicity of AgNP was assessed against Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus. In laboratory, AgNP were highly toxic against larvae and pupae of the three mosquito species. Maximum efficacy was observed against A. stephensi larvae, with LC50 ranging from 16.156 ppm (larva I) to 28.881 ppm (pupa). In the field, a single treatment with AgNP (10 * LC50) in water storage reservoirs was effective against the three mosquito vectors, allowing complete elimination of larval populations after 72 h. In ovicidal experiments, egg hatchability was reduced by 100% after treatment with 30 ppm of AgNP. Ovideterrence assays highlighted that 10 ppm of AgNP reduced oviposition rates of more than 70% in A. aegypti, A. stephensi, and C. quinquefasciatus (OAI = -0.61, 0.63, and -0.58, respectively). Antibacterial properties of AgNP were evaluated against Bacillus subtilis, Klebsiella pneumoniae, and Salmonella typhi using the agar disk diffusion and minimum inhibitory concentration protocol. AgNP tested at 50 ppm evoked growth inhibition zones larger than 5 mm in all tested bacteria. Overall, the chance to use S. muticum-synthesized AgNP for control of mosquito vectors seems promising since they are effective at low doses and may constitute an advantageous alternative to build newer and safer mosquito control tools. This is the first report about ovicidal activity of metal nanoparticles against mosquito vectors. PMID- 26281787 TI - Pneumocystis jirovecii--from a commensal to pathogen: clinical and diagnostic review. AB - Pneumocystis pneumonia is an opportunistic disease caused by invasion of unicellular fungus Pneumocystis jirovecii. Initially, it was responsible for majority of morbidity and mortality cases among HIV-infected patients, which later have been reduced due to the introduction of anti-retroviral therapy, as well as anti-Pneumocystis prophylaxis among these patients. Pneumocystis pneumonia, however, is still a significant cause of mortality among HIV-negative patients being under immunosuppression caused by different factors, such as transplant recipients as well as oncologically treated ones. The issue of pneumocystosis among these people is particularly emphasized in the article, since rapid onset and fast progression of severe symptoms result in high mortality rate among these patients, who thereby represent the group of highest risk of developing Pneumocystis pneumonia. In contrast, fungal invasion in immunocompetent people usually leads to asymptomatic colonization, which frequent incidence among healthy infants has even suggested the possibility of its association with sudden unexpected infant death syndrome. In the face of emerging strains with different epidemiological profiles resulting from genetic diversity, including drug-resistant genotypes, the colonization phenomenon desires particular attention, discussed in this article. We also summarize specific and sensitive methods, required for detection of Pneumocystis invasion and for distinguish colonization from the disease. PMID- 26281788 TI - Reproductive Patterns in the Non-Breeding Season in Asinina de Miranda Jennies. AB - This study aims to characterize the reproductive patterns in Asinina de Miranda jennies during the non-breeding season. Reproductive activity was surveyed in 12 females, aged between 3 and 18 years old, using ultrasound and teasing with a jack. The animals were monitored from September to April, six in each consecutive year. Of these 12 females, nine showed disruption to the normal pattern of ovarian activity during the non-breeding season. Loss of normal cyclicity included anoestrus (41.7%), silent ovulatory oestrus (25%), and persistence of corpus luteum (8.3%). Only three females maintained a regular cyclic pattern with oestrous behaviour during the non-breeding season. Anoestrus began in early November and lasted for an average of 147 +/- 28 days (113-191 days), ending near to the spring equinox. Onset of silent oestrous cycles began more erratically, between October and February. In both groups the first behavioural ovulation of the year occurred around the time of the spring equinox. Disrupted reproductive activity was preceded by a shorter oestrous cycle only in females entering anoestrus. The mean follicle size in the first ovulation of the year was larger than in the reproductive season (44.7 +/- 2.45 mm vs 39.2 +/- 3.60 mm) in anoestrous jennies with protracted oestrus. Though age and body condition score (BCS) were associated, changes in BCS below a threshold of four points (for anoestrus) and five points (for silent oestrus) contributed greatly to disruption of reproductive cycles. BCS in females with regular oestrous cycles during the winter season remained unchanged or exceeded five points prior to the winter solstice. PMID- 26281789 TI - Highlights of the Faraday Discussion on Nanoparticle Synthesis and Assembly, Argonne, USA, April 2015. PMID- 26281791 TI - Verrucous lesions arising in lymphedema and diabetic neuropathy: Elephantiasis nostras verrucosa or verrucous skin lesions on the feet of patients with diabetic neuropathy? AB - Verrucous skin lesions on the feet in diabetic neuropathy (VSLDN) develop in areas with sensory loss in diabetic patients. Although various types of chronic stimulation, such as pressure or friction, are considered an important factor in the development of such lesions, the precise pathogenesis of VSLDN remains obscure, and there is currently no established treatment for this disease. Here, we present a case of VSLDN on the dorsum of the right foot. However, because lymphedema was also observed at the same site, this lesion could also be diagnosed as elephantiasis nostras verrucosa arising in diabetic neuropathy. The lesion was successfully treated with a combination of elastic stocking and mixed killed bacterial suspension and hydrocortisone ointment, which suggested that VSLDN might have been exacerbated by the pre-existing lymphedema. Because various types of chronic stimulation can trigger VSLDN, treatment plans should be devised on a case-by-case basis. Therefore, it is important to investigate the presence of factors that can induce or exacerbate chronic inflammatory stimulation, such as lymphedema in our case, in each patient with VSLDN. PMID- 26281792 TI - Reducing eating disorder risk factors: A pilot effectiveness trial of a train-the trainer approach to dissemination and implementation. AB - OBJECTIVE: Impediments limit dissemination and implementation of evidence-based interventions (EBIs), including lack of sufficient training. One strategy to increase implementation of EBIs is the train-the-trainer (TTT) model. The Body Project is a peer-led body image program that reduces eating disorder (ED) risk factors. This study examined the effectiveness of a TTT model at reducing risk factors in Body Project participants. Specifically, this study examined whether a master trainer could train a novice trainer to train undergraduate peer leaders to administer the Body Project such that individuals who received the Body Project (i.e., participants) would evidence comparable outcomes to previous trials. We hypothesized that participants would evidence reductions in ED risk factors, with effect sizes similar to previous trials. METHOD: Utilizing a TTT model, a master trainer trained a novice trainer to train undergraduate peer leaders to administer the Body Project to undergraduate women. Undergraduate women aged 18 years or older who received the Body Project intervention participated in the trial and completed measures at baseline, post-treatment, and five-month follow-up. Primary outcomes included body dissatisfaction, thin ideal internalization, negative affect, and ED pathology. RESULTS: Participants demonstrated significant reductions in thin ideal internalization, ED pathology and body dissatisfaction at post-treatment and 5-month follow-up. At 5 months, using three different strategies for managing missing data, effect sizes were larger or comparable to earlier trials for 3 out of 4 variables. DISCUSSION: Results support a TTT model for Body Project implementation and the importance of utilizing sensitivity analyses for longitudinal datasets with missing data. PMID- 26281794 TI - The risk of ureteric injury associated with hysterectomy: a 10-year retrospective cohort study. AB - OBJECTIVE: To evaluate the rates of ureteric injury among women undergoing hysterectomy. DESIGN: Retrospective cohort. SETTING: English National Health Service hospitals. POPULATION: Women undergoing hysterectomy in 2001-2010. METHODS: Unadjusted rates of ureteric injury, within 1 year of hysterectomy, calculated by indication and type of procedure. Multivariable logistic regression used to assess the risk of ureteric injury with year of surgery. MAIN OUTCOME MEASURES: Ureteric injury within a year of the hysterectomy. RESULTS: In 2001 2010, 377 073 women underwent hysterectomy, of whom 1792 (0.5%) experienced a ureteric injury. In both benign and malignant groups the rate of injury was higher in 2006-2010 than 2001-2005. After 2006, ureteric injuries were most common for abdominal radical hysterectomy for uterine cancer (10.7%; 95% CI 7.3 15.1%). The proportion of women having a ureteric injury was similar for ovarian and cervical cancer (1.9-4.0% depending on type of procedure). For benign conditions, the rate of injury tended to be lower, typically <1%. Women with endometriosis had the highest risk among this group (1.7% following total abdominal hysterectomy; 95% CI 1.4-2.0%). CONCLUSION: The risk of ureteric injury within 1 year of hysterectomy varied by type of hysterectomy for benign and malignant conditions. The rates of injury have increased between 2001 and 2010. TWEETABLE ABSTRACT: Ten-year study shows ureteric injury rates have increased. PMID- 26281793 TI - Structural basis for the neutralization of MERS-CoV by a human monoclonal antibody MERS-27. AB - The recently reported Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness in humans with an approximately 30% mortality rate. The envelope spike glycoprotein on the surface of MERS-CoV mediates receptor binding, membrane fusion, and viral entry. We previously reported two human monoclonal antibodies that target the receptor binding domain (RBD) of the spike and exhibit strong neutralization activity against live and pesudotyped MERS-CoV infection. Here we determined the crystal structure of MERS-CoV RBD bound to the Fab fragment of MERS-27 antibody at 3.20 A resolution. The MERS-27 epitope in the RBD overlaps with the binding site of the MERS-CoV receptor DPP4. Further biochemical, viral entry, and neutralization analyses identified two critical residues in the RBD for both MERS-27 recognition and DPP4 binding. One of the residues, Trp535, was found to function as an anchor residue at the binding interface with MERS-27. Upon receptor binding, Trp535 interacts with the N-linked carbohydrate moiety of DPP4. Thus, MERS-27 inhibits MERS-CoV infection by directly blocking both protein-protein and protein-carbohydrate interactions between MERS-CoV RBD and DPP4. These results shed light on the molecular basis of MERS-27 neutralization and will assist in the optimization of MERS-27 as a tool to combat MERS-CoV infection. PMID- 26281795 TI - The effects of reinforcement magnitude on skill acquisition for children with autism. AB - We examined the effects of reinforcement magnitude on skill acquisition during discrete-trial training. After conducting a magnitude preference assessment, we compared acquisition during conditions with large and small magnitudes of edible reinforcement to a praise-only condition. Although all participants showed a preference for the large-magnitude reinforcer, preference did not predict the magnitude that produced the fastest skill acquisition. PMID- 26281797 TI - Rights and duties policy implementation in Chile: health-care professionals' perceptions. AB - OBJECTIVE: To explore the perceptions of health professionals in an integrated network of public provision of health services regarding the implementation of the Law on Rights and Duties of People in Chile. METHOD: Qualitative descriptive study. A stratified qualitative sample of 53 professionals from five low complexity centres and one from a high complexity centre, all part of the integrated network of health services in Valdivia, Los Rios Region, Chile, were selected according to the criteria of an overall saturation of the explored dimensions. The information was gathered through a semi-structured, in-depth interview carried out after signing the informed consent. Data were analysed using an inductive approach of content analysis. RESULTS: Three categories emerged from the interviews: conceptualization and knowledge, factors influencing the implementation and recommendations for strengthening the implementation, and seven subcategories. It was highlighted that health professionals in the health care network perceived difficulties in implementing the Law on rights and duties of patients. Among them were the lack of knowledge about the Law, poor exposure and a lack of resources for its implementation. They suggested adapting the infrastructure of the institution and offering training as recommendations to improve the implementation of the Law. CONCLUSIONS: There are hindering factors for the implementation of the Law related to organizational and professional gaps in the institutions providing health care. PMID- 26281798 TI - Assessing an Adolescent's Capacity for Autonomous Decision-Making in Clinical Care. AB - The purpose of this article is to provide policy guidance on how to assess the capacity of minor adolescents for autonomous decision-making without a third party authorization, in the field of clinical care. In June 2014, a two-day meeting gathered 20 professionals from all continents, working in the field of adolescent medicine, neurosciences, developmental and clinical psychology, sociology, ethics, and law. Formal presentations and discussions were based on a literature search and the participants' experience. The assessment of adolescent decision-making capacity includes the following: (1) a review of the legal context consistent with the principles of the Convention on the Rights of the Child; (2) an empathetic relationship between the adolescent and the health care professional/team; (3) the respect of the adolescent's developmental stage and capacities; (4) the inclusion, if relevant, of relatives, peers, teachers, or social and mental health providers with the adolescent's consent; (5) the control of coercion and other social forces that influence decision-making; and (6) a deliberative stepwise appraisal of the adolescent's decision-making process. This stepwise approach, already used among adults with psychiatric disorders, includes understanding the different facets of the given situation, reasoning on the involved issues, appreciating the outcomes linked with the decision(s), and expressing a choice. Contextual and psychosocial factors play pivotal roles in the assessment of adolescents' decision-making capacity. The evaluation must be guided by a well-established procedure, and health professionals should be trained accordingly. These proposals are the first to have been developed by a multicultural, multidisciplinary expert panel. PMID- 26281799 TI - Squared ligament of the elbow: anatomy and contribution to forearm stability. AB - OBJECTIVE: The present study describes the macroscopic and microscopic features of the squared ligament of the elbow (SLE). In addition, the SLE biomechanical behavior and contribution to the forearm stability were also examined. MATERIALS AND METHODS: Ten forearms from freshly frozen cadavers were used for this work. Each forearm was mounted in an experimental frame for quantification of longitudinal and transverse stability. Macroscopic features and biomechanical behavior were analyzed on dynamic videos obtained during forearm rotation. Then, the SLE was harvested from the 10 forearms for microscopic analysis on histological slices stained with hematoxylin-eosin-saffron. RESULTS: Two main SLE configurations were identified. One in which the SLE had three distinct bundles (anterior, middle, posterior) and another in which it was homogeneous. The anterior part of the SLE had a mean length of 11.2 mm (+/-2.4 mm) and a mean width of 1.2 mm (+/-0.2 mm) while the posterior part had a mean length of 9.9 mm (+/-2.2 mm) and a mean width of 1 mm (+/-0.2 mm). Microscopic examination showed that the SLE is composed of a thin layer of arranged collagen fibers. During forearm rotation, the SLE progressively tightens upon pronation and supination by wrapping around the radial neck. Tightening of the SLE during forearm rotation provides transverse and longitudinal stability to the forearm, mainly in maximal pronation and supination. CONCLUSION: The SLE is a true ligament and provides forearm stability when it is stretched in pronation and supination. PMID- 26281800 TI - Persistent hypoglossal artery versus type I proatlantal artery. PMID- 26281801 TI - New tools for emergency managers: an assessment of obstacles to use and implementation. AB - This paper focuses on the role of the formal response community's use of social media and crowdsourcing for emergency managers (EMs) in disaster planning, response and recovery in the United States. In-depth qualitative interviews with EMs on the Eastern seaboard at the local, state and federal level demonstrate that emergency management tools are in a state of transition--from formal, internally regulated tools for crisis response to an incorporation of new social media and crowdsourcing tools. The first set of findings provides insight into why many EMs are not using social media, and describes their concerns that result in fear, uncertainty and doubt. Second, this research demonstrates how internal functioning and staffing issues within these agencies present challenges. This research seeks to examine the dynamics of this transition and offer lessons for how to improve its outcomes--critical to millions of people across the United States. PMID- 26281802 TI - Exposure to Macaque Monkey Bite. AB - BACKGROUND: The herpes B virus is a zoonotic agent that is endemic among macaque monkeys only, but can cause fatal encephalomyelitis in humans. CASE REPORT: A 26 year-old female presented to a U.S. emergency department after being bitten by a wild macaque monkey. The emergency medicine team administered rabies immunoglobulin and rabies vaccine. The team also prescribed acyclovir for prophylactic coverage against herpes B, a deadly zoonotic agent that is endemic among macaque monkeys. A discussion of background, exposure, transmission, symptoms, treatment for herpes B, including latest data available, literature, and Centers for Disease Control and Prevention guidelines are included. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Zoonotic exposures can cause infectious diseases, which are unfamiliar and deadly. The emergency physician's knowledge of the association between the deadly herpes B infection and wild macaque monkey may expedite treatment and be instrumental in patient morbidity and survival. PMID- 26281803 TI - A WINning Technique: The Wire-in-Needle Feasibility Study. AB - BACKGROUND: Dynamic ultrasound guidance reduces complications associated with central venous catheter placement. However, successful central venous cannulation often remains challenging, particularly in hypotensive patients. The new wire-in needle (WIN) technique can further increase periprocedural safety. Here, a needle is "preloaded" with a guidewire that is then advanced toward the tip of needle. The vein is then cannulated using long-axis ultrasound guidance. OBJECTIVE: To evaluate the feasibility and safety profile of the WIN technique. METHODS: Medical students, and resident and attending physicians participated in this study. After a brief lecture and practice session on the WIN technique, they underwent a skills assessment evaluating different aspects of both techniques. Participants then completed a survey assessing their prior experience regarding procedural ultrasound, and their assessment of the WIN technique. RESULTS: Sixty clinicians participated. The assessment of both techniques revealed no significant differences in the number of needle redirections, cannulation attempts, number of arterial punctures, or overall dexterity with the procedure. The WIN technique was faster (45.9 vs. 61.5 s, p = 0.0005) than the traditional technique. More participants confirmed the accurate position of the guidewire in the vein (75% vs. 95%, p = 0.002). More than 90% of study participants met the predefined safety aspects of the WIN technique. Almost all participants reported that they plan on using the WIN technique in their clinical practice. CONCLUSION: This study demonstrates that the WIN technique can be learned quickly and easily by clinicians with various levels of training. In this study, using manikins, it was as successful and safe as the traditional short-axis approach. PMID- 26281804 TI - Oropharyngeal Edema in an 8-Month-Old Girl after Woolly Bear Caterpillar Exposure. AB - BACKGROUND: Lepidopterism refers to the manifestations of contact from any number of moths, butterflies, and caterpillars. Various symptoms have been described, ranging from localized skin irritation to systemic anaphylactic reactions. CASE REPORT: We present a case of airway edema in an 8-month-old child from oral exposure to Woolly Bear Caterpillar (Pyrrharctia Isabella). After prompt emergency department recognition, her symptoms necessitated urgent operating room management by a team of otolaryngologists and close monitoring in a pediatric intensive care unit. A similar presentation in this species has not been described previously in the English literature. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Leptidopterism is rare, but recognition by the emergency practitioner is necessary for prompt and appropriate treatment. Rapid identification by the emergency physician of oral exposure and careful spine removal can be lifesaving in cases of significant oropharyngeal edema. PMID- 26281805 TI - The Use of Intraosseous Fluid Resuscitation in a Pediatric Patient with Ebola Virus Disease. AB - BACKGROUND: Vomiting, diarrhea, and severe dehydration are common manifestations of Ebola virus disease (EVD), leading to its high mortality. Mortality is especially high in patients older than 45 years, younger than 5 years, and in pregnant women and their fetuses. The majority of patients with EVD are not able to tolerate the quantities of oral hydration solutions necessary to rehydrate properly. Although some have speculated that IV and intraosseous lines are not practical in the austere, resource-constrained settings of an Ebola treatment unit during an epidemic, it is necessary to provide parenteral fluids and electrolyte replacements to significantly decrease mortality. Due to the inability to spend long periods of time working in hot environments wearing personal protective equipment, it is necessary to maximize the use of rapidly obtainable and safe parenteral access. CASE REPORT: The authors present a case of a 9-month-old patient with EVD in Sierra Leone in whom an intraosseous line was lifesaving. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians respond to international crises, such as the most recent Ebola epidemic in West Africa. It is important for such responders, as well as their responding organizations, to know and understand that intraosseous access is an important and safe modality to use in patients with EVD and in the austere settings often found in disaster settings. PMID- 26281806 TI - Life, Trauma, Death: A Resident Physician's Perspective. PMID- 26281807 TI - Hypovolemia Resulting in Platypnea-Orthodeoxia Syndrome. AB - BACKGROUND: Platypnea-orthodeoxia syndrome is a rare disease entity that is characterized by dyspnea and desaturation in the upright position that resolves when the patient is in the supine position. CASE REPORT: An 80-year-old man presented with epistaxis but was noted to be hypoxic and was unresponsive to supplemental oxygenation. His oxygen saturation improved with supine positioning, however, which is consistent with platypnea-orthodeoxia syndrome. This improved with overnight intravenous hydration. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: In patients with hypoxia and paradoxical improvement in oxygen saturation with supine positioning, consider platypnea-orthodeoxia as a potential cause. PMID- 26281808 TI - Ambulatory Care Sensitive Hospitalizations Through the Emergency Department by Payer: Comparing 2003 and 2009. AB - BACKGROUND: Ambulatory care sensitive hospitalizations (ACSHs) are hospitalizations that may have been preventable with timely and effective outpatient care. Approximately 75% of all ACSHs occur through the emergency department (ED). ACSHs through the ED (ED ACSHs) have significant implications for costs and ED crowding. OBJECTIVE: This study compares rates of ED ACSHs for 2003 and 2009 among patients 18 to 64 years of age with private insurance, Medicaid, or no insurance. METHODS: Nationally representative estimates of ED ACSHs, defined by the Agency for Healthcare Research and Quality (AHRQ) prevention quality indicators (PQIs), were generated from the 2003 and 2009 Nationwide Inpatient Samples. Census data were used to calculate direct age- and sex-standardized ACSH rates by non-Medicare payers for both years. RESULTS: Between 2003 and 2009, the overall rate of ED ACSHs decreased from 7.6 (95% confidence interval [CI] 7.57-7.75) to 7.3 (95% CI 7.2-7.4) per 1000 18- to 64 year-old non-Medicare patients. ED ASCH rates declined significantly from 42.4 (95% CI 42.0-42.8) to 25.3 (95% CI 25.0-25.6) per 1000 patients with Medicaid, and declined modestly from 3.8 (95% CI 3.8-3.9) to 3.3 (95% CI 3.2-3.4) per 1000 patients with private insurance. However, the ED ACSH rate increased for the uninsured population from 5.4 (95% CI 5.2-5.7) to 6.2 (95% CI 5.9-6.4) per 1000 patients. CONCLUSION: Expansion of Medicaid over the study period was not associated with an increase in ED ACSHs for Medicaid patients. However, an increase in the uninsured population was associated with an increase in the rate of ED ACSH for uninsured patients. PMID- 26281809 TI - Left Ventricle Tissue Doppler Imaging Predicts Disease Severity in Septic Patients Newly Admitted in an Emergency Unit. AB - BACKGROUND: Assessment of sepsis severity is challenging. Available scoring systems require laboratory data. Therefore, a rapid tool would be useful. OBJECTIVE: To determine the role of mitral valve tissue Doppler imaging (TDI) as a prognostic tool in septic patients. METHODS: For this prospective cohort, newly admitted septic patients received TDI measurements of s wave (s), e' wave (e'), and E/e' ratio (E/e') within 5 min of resuscitation. Results were compared with sepsis severity measured by Mortality in Emergency Department Sepsis (MEDS), Simplified Acute Physiology Score (SAPS) 3, and Sequential Organ Failure Assessment (SOFA). RESULTS: Over 3 months, 63 patients were enrolled. TDI parameters correlated with MEDS, SAPS 3, and SOFA (r = -0.53, r = -0.55, r = 0.36, respectively, for s, p < 0.005; r = -0.56, r = -0.49, r = -0.40, respectively, for e', p < 0.005; and r = 0.56; r = 0.48; r = 0.46, respectively, for E/e', p < 0.005). Mean s and e' decreased among sepsis, severe sepsis, and septic shock patients (14.2; 12.05; 10.14 cm/s, respectively, for s, p = 0.0048 and 18.28; 15.14; 12.12 cm/s, respectively, for e', p = 0.003), whereas mean E/e' increased among sepsis stages (4.76; 6.51; and 8.14, respectively, p = 0.001). Mean s and e' were higher in survivors (13.25 vs. 7.33 cm/s, for s, p < 0.0001; and 16.4 vs. 9 cm/s for e', p = 0.0025); mean E/e' was higher in nonsurvivors (10.85 vs. 5.63, p < 0.0001). On univariate analysis, odds ratios (ORs) for death related to s, e', and E/e' were, respectively, 0.517 (95% confidence interval [CI] 0.344-0.775), 0.60 (95% CI 0.433-0.833), and 1.953 (95% CI 1.256-3.008); p < 0.05 for all. Multiple logistic analysis showed an OR of 1.737 (95% CI 1.037 2.907, p = 0.035) for death related to E/e'. CONCLUSION: TDI may be useful to assess disease severity and prognosis in newly diagnosed septic patients. PMID- 26281810 TI - Febrile Man with Pneumoperitoneum. PMID- 26281811 TI - Barriers to Homeless Persons Acquiring Health Insurance Through the Affordable Care Act. AB - BACKGROUND: Medicaid expansion under the Affordable Care Act (ACA) is intended to provide a framework for increasing health care access for vulnerable populations, including the 1.2 million who experience homelessness each year in the United States. OBJECTIVE: We sought to characterize homeless persons' knowledge of the ACA, identify barriers to their ACA enrollment, and determine access to various forms of communication that could be used to facilitate enrollment. METHODS: At an urban county Level I trauma center, we interviewed all noncritically ill adults who presented to the emergency department (ED) during daytime hours and were able to provide consent. We assessed access to communication, awareness of the ACA, insurance status, and barriers preventing subjects from enrolling in health insurance and compared homeless persons' responses with concomitantly enrolled housed individuals. RESULTS: Of the 650 enrolled subjects, 134 (20.2%) were homeless. Homeless subjects were more likely to have never heard of the ACA (26% vs. 10%). "Not being aware if they qualify for Medicaid" was the most common (70%) and most significant (30%) barrier to enrollment reported by uninsured homeless persons. Of homeless subjects who were unsure if they qualified for Medicaid, 91% reported an income < 138% of the federal poverty level, likely qualifying them for enrollment. Although 99% of housed subjects reported access to either phone or internet, only 74% of homeless subjects reported access. CONCLUSIONS: Homeless persons report having less knowledge of the ACA than their housed counterparts, poor understanding of ACA qualification criteria, and limited access to phone and internet. ED-based outreach and education regarding ACA eligibility may increase their enrollment. PMID- 26281812 TI - Progressive Organ Failure After Ingestion of Wild Garlic Juice. AB - BACKGROUND: Wild garlic and related plants are increasingly sought after by fans of natural products. They can be confused with other plants containing colchicine and cause potentially fatal intoxications. CASE REPORT: We report a case of accidental poisoning by Colchicum autumnale, which was mistaken for wild garlic (Allium ursinum). The patient initially presented with mild gastrointestinal symptoms, but progressed rapidly to agranulocytosis, paraparesis, and delirium before the causative agent was identified. The laboratory tests revealed rhabdomyolysis, coagulopathy, alteration of liver tests, and prerenal azotemia. Botanical examination confirmed the incriminated plant (Colchicum autumnale). Serum and urine analysis confirmed the presence of colchicine. The patient required intensive support therapy, and she fully recovered within 8 weeks. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Colchicine poisoning should be considered in the differential diagnosis of patients presenting with gastroenteritis after ingestion of wild garlic. PMID- 26281813 TI - "Why Is This Patient Being Sent Here?": Communication from Urgent Care to the Emergency Department. AB - BACKGROUND: Despite patients' increasing use of urgent care centers (UCC), little is known about how urgent care clinicians communicate with the emergency department (ED). OBJECTIVES: To assess ED clinicians' perceptions of the quality and consistency of communication when patients are referred from UCCs to EDs. METHODS: Emergency medicine department chairs distributed a brief, electronic survey to a statewide sample of ED clinicians via e-mail. The survey included multiple-choice and free-text questions focused on types of communication desired and received from UCCs, types of test results available on transfer, and suggestions for improvement. RESULTS: Of 199 ED clinicians, 102 (51.3%) responded. More than four out of five respondents "somewhat" or "strongly agreed" that each of the following would be helpful: a telephone call, the reason for referral, specific concern, a copy of the chart, and UCC contact information. However, ED clinicians reported not consistently receiving these: only a fifth (21.6%) of clinicians reported receiving the specific concern for their last 5 patients transferred from a UCC, and 34.3% recalled receiving a copy of the chart. Overall, 54.9% reported receiving laboratory test results "often or almost always," 49.0% electrocardiograms, and 44.1% imaging reports. Qualitative analysis revealed several themes: incomplete data when patients are referred; barriers to discussion between ED and urgent care clinicians; and possible solutions to improve communication. CONCLUSIONS: Our findings highlight variation in communication from UCCs to EDs, indicating a need to improve communication standards and practices. We identify several potential ways to improve this clinical information hand-off. PMID- 26281814 TI - The Safety of Topical Anesthetics in the Treatment of Corneal Abrasions: A Review. AB - BACKGROUND: Despite the fact that topical anesthetics provide superb analgesia to the painful eye, they are not prescribed routinely to patients when they are discharged from the emergency department because of concerns for delayed healing and corneal erosion. OBJECTIVE: To summarize the evidence for the safety of topical proparacaine and tetracaine for pain relief in patients with corneal abrasions. METHODS: This is a systematic review looking at the use of topical anesthetic agents in the treatment of corneal abrasions in the emergency department. RESULTS: Our literature search produced two emergency department based, randomized, double blind, placebo-controlled studies on human patients with corneal abrasions. Additionally, we found four studies that investigated the application of topical anesthetics in patients who underwent photorefractive keratectomy. All six studies demonstrated that a short course of dilute topical anesthetic provided efficacious analgesia without adverse effects or delayed epithelial healing. CONCLUSION: Limited available data suggests that the use of dilute topical ophthalmologic proparacaine or tetracaine for a short duration of time is effective, though their safety for outpatient use is inconclusive. PMID- 26281815 TI - Erythema Multiforme. PMID- 26281816 TI - Retrospective Evaluation of Two Fast-track Strategies to Rule Out Acute Coronary Syndrome in a Real-life Chest Pain Population. AB - BACKGROUND: The European Society of Cardiology (ESC) guideline on non-ST elevation acute coronary syndrome (N-STE ACS) proposed a new ACS rule-out protocol. OBJECTIVES: To evaluate this new tool, which uses diagnostic levels of high-sensitivity troponin T (hs-TnT; > 14 ng/L) in a slightly modified version and compare this to a recently proposed approach using undetectable levels of hs TnT to rule out patients. METHODS: There were 534 consecutive patients with suspected ACS included. Protocol 1: symptom duration, hs-TnT at 0 and 6-9 h, Global Registry of Acute Coronary Events (GRACE) score, and symptom status at 6-9 h. Protocol 2: a single blood sample of hs-TnT. The primary endpoint was a discharge diagnosis of ACS by blinded adjudication. Secondary endpoints were ACS re-admission < 30 days and 1-year mortality. RESULTS: Protocol 1 classified 434/534 (81%) patients, with 27.9% being ruled out. All myocardial infarctions were correctly ruled in, but 15 cases of unstable angina were missed, resulting in a sensitivity and negative predictive value of 87.3% (79.6-92.5%) and 87.6% (80.4-92.9%), respectively. Protocol 2 ruled out 17.5% of the population, yielding a sensitivity and negative predictive value of 94.1% (88.2-97.6%) and 90.8% (81.9-96.2%), respectively. Both protocols correctly ruled in 2/3 patients with ACS re-admission < 30 days and 55/56 1-year fatalities. CONCLUSION: The present study confirms the diagnostic value of a modified version of the ESC rule out protocol (Protocol 1) in N-STE ACS patients, but also suggests that a simpler protocol using undetectable levels of hs-TnT (Protocol 2) could provide a similar or even superior sensitivity. PMID- 26281817 TI - A Rare but Lethal Cause of Chest Pain. PMID- 26281818 TI - Facing the Unexpected: Chest Wall Swelling 7 Years After A Stab Injury. PMID- 26281819 TI - Impact of an Opioid Prescribing Guideline in the Acute Care Setting. AB - BACKGROUND: Death from opioid abuse is a major public health issue. The death rate associated with opioid overdose nearly quadrupled from 1999 to 2008. Acute care settings are a major source of opioid prescriptions, often for minor conditions and chronic noncancer pain. OBJECTIVE: Our aim was to determine whether a voluntary opioid prescribing guideline reduces the proportion of patients prescribed opioids for minor and chronic conditions. METHODS: A retrospective chart review was performed on records of adult emergency department visits from January 2012 to July 2014 for dental, neck, back, or unspecified chronic pain, and the proportion of patients receiving opioid prescriptions at discharge was compared before and after the guideline. Attending emergency physicians were surveyed on their perceptions regarding the impact of the guideline on prescribing patterns, patient satisfaction, and physician-patient interactions. RESULTS: In our sample of 13,187 patient visits, there was a significant (p < 0.001) and sustained decrease in rates of opioid prescriptions for dental, neck, back, or unspecified chronic pain. The rate of opioid prescribing decreased from 52.7% before the guideline to 29.8% immediately after its introduction, and to 33.8% at an interval of 12 to 18 months later. The decrease in opioid prescriptions was observed in all of these diagnosis groups and in all age groups. All 31 eligible prescribing physicians completed a survey. The opioid prescribing guideline was supported by 100% of survey respondents. CONCLUSIONS: An opioid prescribing guideline significantly decreased the rates at which opioids were prescribed for minor and chronic complaints in an acute care setting. PMID- 26281820 TI - Risk Factors for Posttraumatic Stress Disorder in Polish Paramedics: A Pilot Study. AB - BACKGROUND: Working as a paramedic carries the risk of witnessing events and personal experiences associated with emergency life-threatening circumstances that may result in symptoms associated with posttraumatic stress. This problem is well known but still underestimated. OBJECTIVES: The specific study objectives were to 1) assess the influence of sociodemographic and occupational factors on posttraumatic stress disorder (PTSD) among paramedics, and 2) suggest preventive strategies in this population. METHODS: This prospective, descriptive study examined a sample of 100 paramedics who agreed to complete the Author Questionnaire comprising demographic questions and the Impact of Event Scale Revised. RESULTS: The total prevalence of PTSD in the examined group was 40.0% (women = 64.3%, men = 36.1%). It was more frequently reported in paramedics working under an employer's contract than among those who were self-employed. It occurred less frequently in persons with more education. Other sociodemographic factors studied showed no significant impact. A statistically significant effect of exposure to certain types of traumatic events on the incidence of PTSD was found. There was no significant correlation between the prevalence of PTSD and the occurrence of problem situations in respondents' workplaces. CONCLUSIONS: Polish paramedics who agreed to take part in the survey were shown to have a high rate of PTSD. Multi-center screening and early supportive management is recommended. PMID- 26281821 TI - Resistance Patterns of Escherichia coli in Women with Uncomplicated Urinary Tract Infection Do Not Correlate with Emergency Department Antibiogram. AB - BACKGROUND: Urine cultures are not always performed for female Emergency Department (ED) patients with uncomplicated urinary tract infection (UTI). Accordingly, hospital, and even ED-specific, antibiograms might be skewed toward elderly patients with many comorbidities and relatively high rates of antimicrobial resistance, and thus do not accurately reflect otherwise healthy women. Our ED antibiogram indicates Escherichia coli resistance rates for ciprofloxacin, levofloxacin, and trimethoprim-sulfamethoxazole (TMP-SMX) of 42%, 26%, and 33%, respectively. OBJECTIVES: This study aims to compare resistance rates of urinary E. coli from otherwise healthy women with uncomplicated UTI and pyelonephritis in the ED to rates in our ED antibiogram. METHODS: Females > 18 years old with acute onset of urinary frequency, urgency, or dysuria with pyuria identified on urinalysis (white blood cell count > 10/high-power field) were prospectively enrolled in the ED of an urban, academic medical center. Exclusion criteria indicating a complicated UTI were consistent with Infectious Diseases Society of America guidelines. Susceptibility patterns of E. coli to ciprofloxacin, levofloxacin, and TMP-SMX in the study group were compared to our ED antibiogram. RESULTS: Forty-five patients grew E. coli. Pyelonephritis was suspected in nine (20%) subjects. Compared with the ED antibiogram, significantly lower rates of resistance to ciprofloxacin (2% vs. 42%, p < 0.001), levofloxacin (2% vs. 26%, p < 0.001), and TMP-SMX (16% vs. 33%, p = 0.016) were observed. Six patients grew non-E. coli uropathogens. All were susceptible to both levofloxacin and TMP-SMX. CONCLUSIONS: ED antibiograms may overestimate resistance rates for uropathogens causing uncomplicated UTIs. In cases where nitrofurantoin cannot be used, fluoroquinolones and possibly TMP-SMX may remain viable options for treatment of uncomplicated UTI and pyelonephritis in women. PMID- 26281822 TI - Acute Myeloid Leukemia in Adolescents and Young Adults Treated in Pediatric and Adult Departments in the Nordic Countries. AB - BACKGROUND: Studies on adolescents and young adults with acute lymphoblastic leukemia suggest better results when using pediatric protocols for adult patients, while corresponding data for acute myeloid leukemia (AML) are limited. PROCEDURE: We investigated disease characteristics and outcome for de novo AML patients 10-30 years old treated in pediatric or adult departments. We included 166 patients 10-18 years of age with AML treated according to the pediatric NOPHO protocols (1993-2009) compared with 253 patients aged 15-30 years treated in hematology departments (1996-2009) in the Nordic countries. RESULTS: The incidence of AML was 4.9/million/year for the age group 10-14 years, 6.5 for 15 18 years, and 6.9 for 19-30 years. Acute promyelocytic leukemia (APL) was more frequent in adults and in females of all ages. Pediatric patients with APL had similar overall survival as pediatric patients without APL. Overall survival at 5 years was 60% (52-68%) for pediatric patients compared to 65% (58-70%) for adult patients. Cytogenetics and presenting white blood cell count were the only independent prognostic factors for overall survival. Age was not an independent prognostic factor. CONCLUSIONS: No difference was found in outcome for AML patients age 10-30 years treated according to pediatric as compared to adult protocols. PMID- 26281823 TI - The Association between Intravitreal Steroids and Post-Injection Endophthalmitis Rates. AB - PURPOSE: To determine whether there is a difference in the risk of endophthalmitis after an intravitreal steroid injection compared with an anti vascular endothelial growth factor (VEGF) agent injection. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 75,249 beneficiaries in a large national US medical claims database representing 406 380 intravitreal injections. METHODS: Data were searched for all intravitreal injections (Current Procedural Terminology 67028) performed between 2003 and 2012. Cohorts were created on the basis of injections using anti-VEGF agents (bevacizumab, ranibizumab, aflibercept, and pegaptanib) and intraocular steroids (triamcinolone and dexamethasone). Endophthalmitis was defined as having a new endophthalmitis diagnosis (International Classification of Diseases 9th Revision 360.0x) and a "tap-and-inject" procedure (Current Procedural Terminology 67015, 67025), a vitrectomy (67036), or an intravitreal antibiotic injection on the same day, between 1 and 14 days post-injection. Exclusion occurred for any history of endophthalmitis, <6 months in the plan, or <1 month follow-up. The main outcome measure was the odds of endophthalmitis using logistic regression while controlling for injection-associated diagnosis, age, race, and gender. RESULTS: A total of 387,714 anti-VEGF injections and 18 666 steroid intravitreal injections were performed and followed by 73 (rate=0.019% or 1/5283 anti-VEGF injections) and 24 (rate=0.13% or 1/778 steroid injections) cases of endophthalmitis, respectively. After controlling for diagnosis, age, race, and gender, the odds ratio (OR) for endophthalmitis occurring was 6.92 (95% confidence interval, 3.54 13.52, P<0.001) times higher post-steroid injection compared with anti-VEGF injections. CONCLUSIONS: The rate of endophthalmitis post-intravitreal steroid injection in a national cohort was 0.13% (1/778 injections). This rate conferred a significantly increased OR of 6.92 for endophthalmitis compared with anti-VEGF agents. PMID- 26281824 TI - [Evidence-based practice competence in undergraduate Nursing Degree students]. AB - AIM: Evidence-based practice (EBP) learning has become a key issue for nurses. An EPB subject was included in the 4(th) year in the new syllabus of the Nursing Degree at University of Murcia (UM). To know the competence level in EBP of undergraduate nursing students at UM and compare the results between all four years. METHOD: Observational descriptive study with a cross-sectional approach. STUDY POPULATION: undergraduate nursing students from all four years at Nursing Degree at the Faculty of Social and Healthcare Science at UM in the year 2013-14. EBP evaluation of competence of the nursing students consisted of attitude, skills and knowledge on EBP. A validated questionnaire, the EBP-COQ, was used. The scale range is 1 point "lowest level" to 5 points "higher level".The SPSS 21.0 program has been used to carry out descriptive and bivariate analyses. RESULTS: 144 students were included, 76.4% was female, and the median age was 23 years, 84.7% attended more than 75% class hours. The mean differences in the questionnaire between first and fourth years were 0.58 points in attitude, 0.60 in skills, 1.6 in knowledge and 0.83 in global competence in EBP. Significant differences in mean scores between the fourth and the remaining years in the global competence in EBP were observed, as well as in the three dimensions (p <0.05). CONCLUSION: The undergraduate-nursing students studied here have acquired an appropriate competence level in EBP, with a gradual increase by year. The biggest increase was in the fourth year students. PMID- 26281825 TI - Quality of Life in Relation to Pain Response to Radiation Therapy for Painful Bone Metastases. AB - PURPOSE: To study quality of life (QoL) in responders and nonresponders after radiation therapy for painful bone metastases; and to identify factors predictive for a pain response. PATIENTS AND METHODS: The prospectively collected data of 956 patients with breast, prostate, and lung cancer within the Dutch Bone Metastasis Study were used. These patients, irradiated for painful bone metastases, rated pain, QoL, and overall health at baseline and weekly afterward for 12 weeks. Using generalized estimating equations analysis, the course of QoL was studied, adjusted for primary tumor. To identify predictive variables, proportional hazard analyses were performed, taking into account death as a competing risk, and C-statistics were calculated for discriminative value. RESULTS: In total, 722 patients (76%) responded to radiation therapy. During follow-up, responders had a better QoL in all domains compared with nonresponders. Patients with breast or prostate cancer had a better QoL than patients with lung cancer. In multivariate analysis, baseline predictors for a pain response were breast or prostate cancer as primary tumor, younger age, good performance status, absence of visceral metastases, and using opioids. The discriminative ability of the model was low (C-statistic: 0.56). CONCLUSIONS: Responding patients show a better QoL after radiation therapy for painful bone metastases than nonresponders. Our model did not have enough discriminative power to predict which patients are likely to respond to radiation therapy. Therefore, radiation therapy should be offered to all patients with painful bone metastases, aiming to decrease pain and improve QoL. PMID- 26281826 TI - Radical Radiation Therapy After Lung-Sparing Surgery for Malignant Pleural Mesothelioma: Survival, Pattern of Failure, and Prognostic Factors. AB - PURPOSE: To prospectively assess the survival, patterns of failure, and prognostic factors in a large cohort of patients with malignant pleural mesothelioma who had undergone a novel trimodal therapeutic approach, including lung-sparing surgery, chemotherapy, and subsequent treatment with high doses of intensity modulated radiation therapy (IMRT) to the whole hemithorax. METHODS AND MATERIALS: The analysis was conducted on the data from 69 patients. Of the 69 patients, 35 underwent extended pleurectomy/decortication (P/D), with resection of the entire pleura, along with portions of the pericardium and diaphragm and 34, partial pleurectomy, defined as partial removal of parietal or visceral pleura for diagnostic purposes, leaving gross tumor behind in all cases. All patients received cisplatin/pemetrexed chemotherapy. Postoperative IMRT was delivered to the entire hemithorax, excluding the intact lung. The IMRT dose was 50 Gy in 25 fractions. Any fluorodeoxyglucose-avid areas or regions of particular concern for residual disease were given a simultaneous boost to 60 Gy. RESULTS: The median follow-up duration was 19 months. No difference was seen in overall survival and locoregional control between the extended P/D group and the partial pleurectomy group. The 2-year overall survival was 65% and 58% in the extended P/D and partial pleurectomy groups, respectively (P=.94). Locoregional control at 2 years was 65% and 64% in the extended P/D and partial pleurectomy groups, respectively (P=.75). The predominant pattern of failure was distant: 19 patients (27.5%) developed distant metastases as the first site of relapse. Gross residual disease after surgery was significantly associated with overall survival (hazard ratio 3.45). One fatal pneumonitis was reported; 14 cases (20%) of grade 2 to 3 pneumonitis were documented. CONCLUSIONS: Radical IMRT after lung-sparing surgery and chemotherapy for malignant pleural mesothelioma leads to promising survival results and acceptable toxicity rates. The similarity of survival between patients treated with extended P/D or partial pleurectomy observed in our study is intriguing. PMID- 26281827 TI - Cartographic Mapping and Travel Burden to Assess and Develop Strategies to Improve Minority Access to National Cancer Clinical Trials. AB - PURPOSE: To assess how accrual to clinical trials is related to US minority population density relative to clinical trial site location and distance traveled to Radiation Therapy Oncology Group (RTOG) clinical trial sites. METHODS AND MATERIALS: Data included member site address and ZIP codes, patient accrual, and patient race or ethnicity and ZIP code. Geographic Information System maps were developed for overall, Latino, and African American accrual to trials by population density. The Kruskal-Wallis test was used to assess differences in distance traveled by site, type of trial, and race or ethnicity. RESULTS: From 2006 to 2009, 6168 patients enrolled on RTOG trials. The RTOG US site distribution is generally concordant with overall population density. Sites with highest accrual are located throughout the United States and parts of Canada and do not cluster, nor does highest minority accrual cluster in areas of highest US minority population density. Of the 4913 US patients with complete data, patients traveled a median of 11.6 miles to participate in clinical trials. Whites traveled statistically longer distances (12.9 miles; P<.0001) to participate, followed by Latinos (8.22 miles) and African Americans (5.85 miles). Patients were willing to drive longer distances to academic sites than community sites, and there was a trend toward significantly longer median travel for therapeutic versus cancer control or metastatic trials. CONCLUSIONS: Location matters, but only to a degree, for minority compared with nonminority participation in clinical trials. Geographic Information System tools help identify gaps in geographic access and travel burden for clinical trials participation. Strategies that emerged using these tools are discussed. PMID- 26281828 TI - Impact of Using Audit Data to Improve the Evidence-Based Use of Single-Fraction Radiation Therapy for Bone Metastases in British Columbia. AB - PURPOSE: To assess the impact of a population-based intervention to increase the consistency and use of single-fraction radiation therapy (SFRT) for bone metastases. METHODS AND MATERIALS: In 2012, an audit of radiation therapy prescriptions for bone metastases in British Columbia identified significant interphysician and -center (26%-73%) variation in the use of SFRT. Anonymous physician-level and identifiable regional cancer center SFRT use data were presented to all radiation oncologists, together with published guidelines, meta analyses, and recommendations from practice leaders. The use of SFRT for bone metastases from 2007 through 2011 was compared with use of SFRT in 2013, to assess the impact of the audit and educational intervention. Multilevel logistic regression was used to assess the relationship between the usage of SFRT and the timing of the radiation while controlling for potentially confounding variables. Physician and center were included as group effects to account for the clustered structure of the data. RESULTS: A total of 16,898 courses of RT were delivered from 2007 through 2011, and 3200 courses were delivered in 2013. The rates of SFRT use in 2007, 2008, 2009, 2010, 2011, and 2013 were 50.5%, 50.9%, 48.3%, 48.5%, 48.0%, and 59.7%, respectively (P<.001). Use of SFRT increased in each of 5 regional centers: A: 26% to 32%; B: 36% to 56%; C: 39% to 57%; D: 49% to 56%; and E: 73% to 85.0%. Use of SFRT was more consistent; 3 of 5 centers used SFRT for 56% to 57% of bone metastases RT courses. The regression analysis showed strong evidence that the usage of SFRT increased after the 2012 intervention (odds ratio 2.27, 95% confidence interval 2.06-2.50, P<.0001). CONCLUSION: Assessed on a population basis, an audit-based intervention increased utilization of SFRT for bone metastases. The intervention reversed a trend to decreasing SFRT use, reduced costs, and improved patient convenience. This suggests that dissemination of programmatic quality indicators in oncology can lead to increased utilization of evidence-based practice. PMID- 26281829 TI - Response to Hron et al. AB - Hron et al. provide transcriptome evidence that three (1.1 %) of the 274 genes reported by Lovell et al. as missing in birds may actually be 'hidden' as a result of high GC content. Although this factor may explain some gene absences from genomic assemblies, we believe it is insufficient to account for the extensive syntenic losses described in Lovell et al. Please see related article: www.dx.doi.org/10.1186/s13059-015-0724-z. PMID- 26281830 TI - Elevated expression of periostin in diabetic cardiomyopathy and the effect of valsartan. AB - BACKGROUND: Periostin, an extracellular matrix protein, plays a significant role in adverse cardiac remodeling. However, no report has documented the function of periostin in left ventricular remodeling of streptozototin (STZ)-induced diabetic rats. The aim of the present study was to observe the expression of periostin in Wistar rat's myocardium of diabetic cardiomyopathy (DCM) and the effect of valsartan on it. METHODS: Immunohistochemistry, real-time polymerase chain reaction, and Western blot analysis were used to determine the degree of expression and location of periostin, transforming growth factor (TGF)-beta1, TGF beta1 type II receptor (TGF-beta1 R II), and Type I and III collagens in the myocardium of STZ-induced diabetic rats. RESULTS: Periostin, TGF-beta1, TGF-beta1 R II, and Type I and III collagens were significantly increased in the myocardium of diabetic rats compared with control group on both messenger ribonucleic acid and protein levels. In addition, diabetic rats treated with valsartan could have reduced expression of periostin and improved cardiac remodeling of DCM. CONCLUSIONS: Periostin may play a crucial role in cardiac remodeling and myocardial interstitial fibrosis process of DCM and it could be one of the important mechanisms for valsartan to improve the ventricular remodeling of DCM. PMID- 26281831 TI - Archival search for historical atypical scrapie in sheep reveals evidence for mixed infections. AB - Natural scrapie in sheep occurs in classical and atypical forms, which may be distinguished on the basis of the associated neuropathology and properties of the disease-associated prion protein on Western blots. First detected in 1998, atypical scrapie is known to have occurred in UK sheep since the 1980s. However, its aetiology remains unclear and it is often considered as a sporadic, non contagious disease unlike classical scrapie which is naturally transmissible. Although atypical scrapie tends to occur in sheep of prion protein (PRNP) genotypes that are different from those found predominantly in classical scrapie, there is some overlap so that there are genotypes in which both scrapie forms can occur. In this search for early atypical scrapie cases, we made use of an archive of fixed and frozen sheep samples, from both scrapie-affected and healthy animals (~1850 individuals), dating back to the 1960s. Using a selection process based primarily on PRNP genotyping, but also on contemporaneous records of unusual clinical signs or pathology, candidate sheep samples were screened by Western blot, immunohistochemistry and strain-typing methods using tg338 mice. We identified, from early time points in the archive, three atypical scrapie cases, including one sheep which died in 1972 and two which showed evidence of mixed infection with classical scrapie. Cases with both forms of scrapie in the same animal as recognizable entities suggest that mixed infections have been around for a long time and may potentially contribute to the variety of scrapie strains. PMID- 26281832 TI - Measuring depression with CES-D in Chinese patients with type 2 diabetes: the validity and its comparison to PHQ-9. AB - BACKGROUND: The validity of the 20-item Center for Epidemiological Studies Depression (CES-D) scale for depression screening in Hong Kong Chinese patients with type 2 diabetes remains unknown. We aimed to validate CES-D, compare its psychometric properties with the 9-item Patient Health Questionnaire (PHQ-9), and explore whether one of the two is more suitable for depression screening in Chinese patients with type 2 diabetes. METHODS: Between June 2010 and July 2011, 545 consecutive Chinese patients with type 2 diabetes who underwent structured comprehensive assessments completed the CES-D and PHQ-9. Forty patients were retested within 2-4 weeks by telephone interview and 97 patients were randomly selected to undergo the Mini International Neuropsychiatric Interview (MINI) by psychiatrists for clinical diagnosis of depression. RESULTS: The internal consistency (Cronbach's alpha) of CES-D was 0.85, with a test-retest correlation coefficient of 0.64. The area under the curve for CES-D compared to the clinical diagnosis of major depression was 0.85. A cut-off score of >=21 for CES-D provided the optimal balance between sensitivity (78.3 %) and specificity (74.3 %) and identified 17.8 % (n = 97) of patients with depression. CES-D and PHQ-9 showed moderate agreement in depression screening (Cohen's Kappa: 0.45). Compared to non-depressed patients, those who screened positive by PHQ-9 had a higher HbA1c whereas the glycemic differences were not significant when using CES-D. CONCLUSION: The CES-D is a valid screening tool for depression in Chinese type 2 diabetic patients although the PHQ-9 was more discriminative in identifying those with suboptimal glycemic control. PMID- 26281833 TI - Randomized multicenter follow-up trial on the effect of radiotherapy on painful heel spur (plantar fasciitis) comparing two fractionation schedules with uniform total dose: first results after three months' follow-up. AB - BACKGROUND: Our first trial on radiotherapy for painful heel spur published in 2012 comparing the analgesic effect of a standard dose (6 * 1.0 Gy within three weeks) to that of a very low one (6 * 0.1 Gy within three weeks) resulted in a highly significant superiority of the standard dose arm. In the meantime, experimental data have shown that lower single doses in the range of 0.5 - 0.7 Gy might be even more effective than the current standard dose of 1.0 Gy. Therefore, we conducted a second trial comparing the analgesic effect of standard single doses of 1.0 Gy to that of low single doses of 0.5 Gy using uniform total doses of 6 Gy. PATIENTS AND METHODS: One hundred twenty-seven patients were randomized to receive radiation therapy either with a total dose of 6.0 Gy applied in 6 fractions of 1.0 Gy twice weekly (standard dose) or with the same total dose applied in 12 fractions of 0.5 Gy three times weekly (experimental dose). In all patients lateral opposing 6MV photon beams were used. The results were measured using Visual analogue scale (VAS), Calcaneodynia score (CS) and SF-12 health survey. The first phase of this trial ended after a three months' follow-up; it will be continued up to 48 weeks. RESULTS: Nine patients had to be excluded after randomization either due to the withdrawal of informed consent to radiotherapy by the patients or radiotherapy with an incorrect dosage. The groups were comparable concerning biographical and disease data. The mean calcaneodynia score (CS) was higher in the experimental group (p = 0.002). After three months' follow-up, we saw a very favorable pain relief in both arms (decline of VAS score: standard arm 42 points, experimental arm 44 points (n.s.), but we did not notice any statistically significant difference between the arms neither concerning the pain parameters nor the quality of life parameters. No relevant acute side effects were recorded. CONCLUSIONS: Favorable laboratory results could not be translated into an enhanced pain relief in our patients. This trial was terminated after the interim analysis (127 patients randomized). Further trials will be necessary to explore the best fractionation schedule. This trial has been approved by the expert panel of the DEGRO as well as by the Ethics committee of the Saarland Physicians' chamber. TRIAL REGISTRATION: Current trial registration at German Clinical Trials Register with the number DRKS00004458. PMID- 26281834 TI - Insulin and IGF-1, but not 17beta-estradiol, alter the subcellular localization of MIER1alpha in MCF7 breast carcinoma cells. AB - BACKGROUND: MIER1alpha is a transcriptional regulator that interacts with estrogen receptor alpha and inhibits estrogen-stimulated growth of breast carcinoma cells. Interestingly, analysis of MIER1alpha subcellular localization in breast samples revealed a stepwise shift from the nucleus to the cytoplasm during progression to invasive carcinoma. Previously, we demonstrated that MIER1alpha is nuclear in MCF7 cells yet it does not contain a nuclear localization signal. Instead MIER1alpha is targeted to the nucleus through interaction and co-transport with HDAC 1 and 2. RESULTS: In this study, we demonstrate that treatment of MCF7 breast carcinoma cells with either insulin or insulin-like growth factor affects the subcellular localization of MIER1alpha. Both factors reduce the percentage of cells with nuclear MIER1alpha from 81 and 89 to 41 and 56%, respectively. Treatment with 17beta-estradiol, on the other hand, had no effect and MIER1alpha remained nuclear. CONCLUSIONS: Our data demonstrate that insulin and IGF-1 can contribute to loss of nuclear MIER1alpha in the MCF7 breast carcinoma cell line. PMID- 26281835 TI - Editorial: Current Issues and Future Directions in Paediatric Imaging. PMID- 26281836 TI - Early functional rehabilitation or cast immobilisation for the postoperative management of acute Achilles tendon rupture? A systematic review and meta analysis of randomised controlled trials. AB - OBJECTIVE: To determine which postoperative rehabilitation regime is superior following surgical repair of acute Achilles tendon rupture. The primary outcomes were patient safety and satisfaction. DESIGN: Intervention meta-analysis. DATA SOURCES: The MEDLINE and CINAHL electronic databases were searched from their date of inception until June 2015 using keywords related to acute Achilles tendon rupture, surgical repair and rehabilitation. The electronic database search was supplemented with forward citation tracking using the Web of Science. ELIGIBILITY CRITERIA: Randomised controlled trials comparing clinical and/or patient-reported outcomes between patients receiving early functional postoperative ankle motion and weight bearing (bracing group), and traditional ankle immobilisation with a non-weight bearing rigid cast (cast group) were eligible for inclusion. Fourteen articles were identified as potentially eligible; 10 sufficient-quality randomised controlled trials involving 570 patients were included for meta analysis. MAIN RESULTS: A high proportion of patients were able to return to prior employment and sporting activity in both groups. Five of the six trials measuring the time interval showed a faster return to prior sporting level in the bracing group. Subjective patient outcomes were significantly better in the bracing group (for good and excellent results, p=0.01; OR, 3.13; 95% CI 1.30 to 7.53). There was no difference in major complications between the two groups (p=0.21; RD, -0.03; 95% CI -0.06 to 0.01). Dynamometry and anthropometry measurements favoured functional rehabilitation at 6-12 weeks postoperation; however, by 6 months postoperative, the differences were negligible. CONCLUSIONS: Compared to traditional ankle immobilisation, with a non-weight bearing cast following surgical repair of acute Achilles tendon rupture, early dynamic functional rehabilitation is as safe with higher patient satisfaction. PMID- 26281837 TI - Caring for Patients With Advanced Cancer: The Role of the Chair, and Other Reflections From 3 Decades in the Clinic. PMID- 26281838 TI - Treatment of Peripheral T-Cell Lymphoma: Many Shades of Gray. AB - Previously obscured within other designations of aggressive lymphomas, peripheral T-cell lymphoma (PTCL) now represents 23 different subtypes of non-Hodgkin lymphoma (NHL). Despite the many subtypes now recognized, PTCL represents only approximately 10% of all NHL cases diagnosed. Positron emission tomography/computed tomography has become essential to accurate staging and response-evaluation for PTCL. In comparison to aggressive B-cell NHL, patients with PTCL will more often be refractory to initial therapy, and chemosensitive patients will have shorter disease-free periods. Anthracycline-based regimens, often with the inclusion of etoposide, are commonly used during induction therapy. Consolidation with high-dose therapy and autologous stem cell transplantation (ASCT) in first chemosensitive remission appears to provide the best outcome in common nodal PTCL subtypes. The commonly defined nodal subtypes are PTCL not otherwise specified, angioimmunoblastic T-cell lymphoma, and anaplastic lymphoma kinase (ALK)-positive or ALK-negative anaplastic large-cell lymphoma (ALCL). Four agents have been approved by the US Food and Drug Administration for use in the relapsed/refractory (rel/ref) setting, including belinostat (2014), romidepsin (2011), brentuximab vedotin (2011), and pralatrexate (2009). Brentuximab vedotin was approved only for the ALCL subtype. These agents continue to be studied as combinations in the rel/ref setting and as additions or substitutions for other agents in upfront multiagent chemotherapy regimens. Patients who have responded to treatment in the rel/ref setting and are considered transplant-eligible should be considered for allogeneic stem cell transplantation, especially those with previous ASCT. Upfront allogeneic stem cell transplantation remains a research question in the majority of PTCL subtypes, but data are emerging. PMID- 26281839 TI - Therapy for Peripheral T-Cell Lymphomas: Where We Are and Where We Hope to Be. PMID- 26281840 TI - Improving Long-Term Survival in Patients With Locally Advanced Pancreatic Cancer via the Delivery of Definitive Radiotherapy Doses. PMID- 26281841 TI - Advance Care Planning Discussions: Why They Should Happen, Why They Don't, and How We Can Facilitate the Process. AB - Recent data suggest that we are not successfully getting the message across about the importance of advance care planning for patients who have a life-ending illness. Half to three-quarters of patients with incurable cancer think that they might be cured by chemotherapy, radiation, or surgery. The source of this denial may lie with them, it may be traceable to their physicians, or it may be a combination of the two. This avoidance has consequences, since those patients with "prognostic awareness" have end-of-life care pathways that involve little use of the hospital, ICU, end-of-life chemo, or "codes" with almost no chance of success, and much more dying at home with hospice care. If we can successfully initiate advance care planning discussions with our patients and families, their end-of-life processes will improve, resulting in better care, less use of the hospital, and more honoring of newly discerned choices. We show how this can be done in regular oncology practice by introducing the Johns Hopkins "Palliative Care Temporary Tattoo" and by providing some ways to discuss cardiopulmonary resuscitation in settings where it will not be helpful. PMID- 26281842 TI - Advance Care Planning: We Can Do It! PMID- 26281843 TI - Biphenotypic extramedullary blast crisis of chronic myeloid leukemia with variant Philadelphia chromosome translocation. PMID- 26281844 TI - A Multidisciplinary Approach to Perianal and Intra-Abdominal Infections in the Neutropenic Cancer Patient. AB - The chemotherapeutic treatment of both hematologic and solid organ malignancies has increased in recent decades, resulting in increased neutropenia-related perianal and intra-abdominal infections. Nearly 30% of neutropenia-related infections arise in the gastrointestinal tract. The management of these patients is often not straightforward, and the indications for and timing of surgical intervention continue to be unclear. The management strategy must take into account such factors as recent chemotherapy toxicity, stage and prognosis of the malignancy, performance status, comorbidities, degree of neutropenia, immunosuppression, thrombocytopenia, and corticosteroid use. The degree and duration of neutropenia is a key determinant of infection resolution. The focus of this review will be the multidisciplinary approach to management of anorectal infection, neutropenic enterocolitis, appendicitis, and cholecystitis in the neutropenic cancer patient. PMID- 26281845 TI - ACR Appropriateness Criteria(r) Resectable Stomach Cancer. AB - For resectable gastric cancer, perioperative chemotherapy or adjuvant chemoradiation with chemotherapy are standards of care. The decision making for adjuvant therapeutic management can depend on the stage of the cancer, lymph node positivity, and extent of surgical resection. After gastric cancer resection, postoperative chemotherapy combined with chemoradiation should be incorporated in cases of D0 lymph node dissection, positive regional lymph nodes, poor clinical response to induction chemotherapy, or positive margins. In the setting of a D2 lymph node dissection, especially those with negative regional lymph nodes, adjuvant chemotherapy alone could be considered. The American College of Radiology (ACR) Appropriateness Criteria(r) are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review includes an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. PMID- 26281846 TI - In Vivo Imaging of Human MDR1 Transcription in the Brain and Spine of MDR1 Luciferase Reporter Mice. AB - P-glycoprotein (Pgp) [the product of the MDR1 (ABCB1) gene] at the blood-brain barrier (BBB) limits central nervous system (CNS) entry of many prescribed drugs, contributing to the poor success rate of CNS drug candidates. Modulating Pgp expression could improve drug delivery into the brain; however, assays to predict regulation of human BBB Pgp are lacking. We developed a transgenic mouse model to monitor human MDR1 transcription in the brain and spinal cord in vivo. A reporter construct consisting of ~10 kb of the human MDR1 promoter controlling the firefly luciferase gene was used to generate a transgenic mouse line (MDR1-luc). Fluorescence in situ hybridization localized the MDR1-luciferase transgene on chromosome 3. Reporter gene expression was monitored with an in vivo imaging system following D-luciferin injection. Basal expression was detectable in the brain, and treatment with activators of the constitutive androstane, pregnane X, and glucocorticoid receptors induced brain and spinal MDR1-luc transcription. Since D-luciferin is a substrate of ABCG2, the feasibility of improving D luciferin brain accumulation (and luciferase signal) was tested by coadministering the dual ABCB1/ABCG2 inhibitor elacridar. The brain and spine MDR1-luc signal intensity was increased by elacridar treatment, suggesting enhanced D-luciferin brain bioavailability. There was regional heterogeneity in MDR1 transcription (cortex > cerebellum) that coincided with higher mouse Pgp protein expression. We confirmed luciferase expression in brain vessel endothelial cells by ex vivo analysis of tissue luciferase protein expression. We conclude that the MDR1-luc mouse provides a unique in vivo system to visualize MDR1 CNS expression and regulation. PMID- 26281847 TI - Positive selection in development and growth rate regulation genes involved in species divergence of the genus Radix. AB - BACKGROUND: Life history traits like developmental time, age and size at maturity are directly related to fitness in all organisms and play a major role in adaptive evolution and speciation processes. Comparative genomic or transcriptomic approaches to identify positively selected genes involved in species divergence can help to generate hypotheses on the driving forces behind speciation. Here we use a bottom-up approach to investigate this hypothesis by comparative analysis of orthologous transcripts of four closely related European Radix species. RESULTS: Snails of the genus Radix occupy species specific distribution ranges with distinct climatic niches, indicating a potential for natural selection driven speciation based on ecological niche differentiation. We then inferred phylogenetic relationships among the four Radix species based on whole mt-genomes plus 23 nuclear loci. Three different tests to infer selection and changes in amino acid properties yielded a total of 134 genes with signatures of positive selection. The majority of these genes belonged to the functional gene ontology categories "reproduction" and "genitalia" with an overrepresentation of the functions "development" and "growth rate". CONCLUSIONS: We show here that Radix species divergence may be primarily enforced by selection on life history traits such as (larval-) development and growth rate. We thus hypothesise that life history differences may confer advantages under the according climate regimes, e.g., species occupying warmer and dryer habitats might have a fitness advantage with fast developing susceptible life stages, which are more tolerant to habitat desiccation. PMID- 26281848 TI - Analysis of Polygenic Mutants Suggests a Role for Mediator in Regulating Transcriptional Activation Distance in Saccharomyces cerevisiae. AB - Studies of natural populations of many organisms have shown that traits are often complex, caused by contributions of mutations in multiple genes. In contrast, genetic studies in the laboratory primarily focus on studying the phenotypes caused by mutations in a single gene. However, the single mutation approach may be limited with respect to the breadth and degree of new phenotypes that can be found. We have taken the approach of isolating complex, or polygenic mutants in the lab to study the regulation of transcriptional activation distance in yeast. While most aspects of eukaryotic transcription are conserved from yeast to human, transcriptional activation distance is not. In Saccharomyces cerevisiae, the upstream activating sequence (UAS) is generally found within 450 base pairs of the transcription start site (TSS) and when the UAS is moved too far away, activation no longer occurs. In contrast, metazoan enhancers can activate from as far as several hundred kilobases from the TSS. Previously, we identified single mutations that allow transcription activation to occur at a greater-than-normal distance from the GAL1 UAS. As the single mutant phenotypes were weak, we have now isolated polygenic mutants that possess strong long-distance phenotypes. By identification of the causative mutations we have accounted for most of the heritability of the phenotype in each strain and have provided evidence that the Mediator coactivator complex plays both positive and negative roles in the regulation of transcription activation distance. PMID- 26281850 TI - Heart rate variability as a potential indicator of positive valence system disturbance: A proof of concept investigation. AB - One promising avenue toward a better understanding of the pathophysiology of positive emotional disturbances is to examine high-frequency heart rate variability (HRV-HF), which has been implicated as a potential physiological index of disturbances in positive emotional functioning. To date, only a few psychopathology relevant studies have systematically quantified HRV-HF profiles using more ecologically valid methods in everyday life. Using an experience sampling approach, the present study examined both mean levels and intra individual variability of HRV-HF - as well as comparison measures of cardiovascular arousal, sympathetic activity, and gross somatic movement - in everyday life, using ambulatory psychophysiological measurement across a six-day consecutive period among a spectrum of community adult participants with varying degrees of positive valence system disturbance, including adults with bipolar I disorder (BD; n=21), major depressive disorder (MDD; n=17), and healthy non psychiatric controls (CTL; n=28). Groups did not differ in mean HRV-HF, but greater HRV-HF instability (i.e., intra-individual variation in HRV-HF) was found in the BD compared to both MDD and CTL groups. Subsequent analyses suggested that group differences in HRV-HF variability were largely accounted for by variations in clinician-rated manic symptoms. However, no association was found between HRV HF variability and dimensional measures of positive affectivity. This work provides evidence consistent with a quadratic relationship between HRV-HF and positive emotional disturbance and represents a valuable step toward developing a more ecologically valid model of positive valence system disturbances and their underlying psychophysiological mechanisms within an RDoC framework. PMID- 26281849 TI - Construction and comparative evaluation of different activity detection methods in brain FDG-PET. AB - AIM: We constructed and evaluated reference brain FDG-PET databases for usage by three software programs (Computer-aided diagnosis for dementia (CAD4D), Statistical Parametric Mapping (SPM) and NEUROSTAT), which allow a user independent detection of dementia-related hypometabolism in patients' brain FDG PET. METHODS: Thirty-seven healthy volunteers were scanned in order to construct brain FDG reference databases, which reflect the normal, age-dependent glucose consumption in human brain, using either software. Databases were compared to each other to assess the impact of different stereotactic normalization algorithms used by either software package. In addition, performance of the new reference databases in the detection of altered glucose consumption in the brains of patients was evaluated by calculating statistical maps of regional hypometabolism in FDG-PET of 20 patients with confirmed Alzheimer's dementia (AD) and of 10 non-AD patients. Extent (hypometabolic volume referred to as cluster size) and magnitude (peak z-score) of detected hypometabolism was statistically analyzed. RESULTS: Differences between the reference databases built by CAD4D, SPM or NEUROSTAT were observed. Due to the different normalization methods, altered spatial FDG patterns were found. When analyzing patient data with the reference databases created using CAD4D, SPM or NEUROSTAT, similar characteristic clusters of hypometabolism in the same brain regions were found in the AD group with either software. However, larger z-scores were observed with CAD4D and NEUROSTAT than those reported by SPM. Better concordance with CAD4D and NEUROSTAT was achieved using the spatially normalized images of SPM and an independent z score calculation. The three software packages identified the peak z-scores in the same brain region in 11 of 20 AD cases, and there was concordance between CAD4D and SPM in 16 AD subjects. CONCLUSION: The clinical evaluation of brain FDG PET of 20 AD patients with either CAD4D-, SPM- or NEUROSTAT-generated databases from an identical reference dataset showed similar patterns of hypometabolism in the brain regions known to be involved in AD. The extent of hypometabolism and peak z-score appeared to be influenced by the calculation method used in each software package rather than by different spatial normalization parameters. PMID- 26281851 TI - Psychological status of patients with nephrotic syndrome undergoing percutaneous renal biopsy. AB - BACKGROUND: Nephrotic syndrome (NS) is a common clinical disease with four main clinical manifestations: hypoalbuminemia (<30 g/L), macro-proteinuria (>3.5 g/24 h), edema, and hyperlipidemia. There is a variety of pathological types that are associated with NS. Percutaneous renal biopsy (PRB) plays an important role in clinical practice in that it can be used to establish a histological diagnosis, to provide information for an ultimate NS diagnosis, and subsequent prognosis. Our aim was to observe the psychological status of patients with NS before and after PRB and investigate the factors affecting their psychological status. METHODS: Two hundred and thirty-five patients with NS were enrolled in the present study. We evaluated the psychological status of patients 24 hours before and 6 hours after PRB by using the Symptom Check List-90 and State-Trait Anxiety Inventory. RESULTS: We analyzed the factors affecting the psychological status of the study participants before and after this important NS procedure. Before the PRB procedure was administered, the factorial anxiety and phobic anxiety scores were higher than normal (p < 0.0.5). After PRB, only anxiety was determined to be higher than normal in the somatization score (p < 0.05). In general, there were higher scores among males rather than the female study participants (p < 0.05). Scores of all indices decreased significantly in all patients after PRB (p < 0.05). CONCLUSION: Psychological status was common in patients who underwent PRB and were affected by many factors. PMID- 26281852 TI - Fibre intake and incident colorectal cancer depending on fibre source, sex, tumour location and Tumour, Node, Metastasis stage. AB - Studies on fibre intake and incident colorectal cancer (CRC) indicate inverse associations. Differences by tumour stage have not been examined. We examined associations between fibre intake and its sources, and incidental CRC. Separate analyses were carried out on the basis of sex, tumour location and the Tumour, Node, Metastasis (TNM) classification. The Malmo Diet and Cancer Study is a population-based cohort study, including individuals aged 45-74 years. Dietary data were collected through a modified diet history method. The TNM classification was obtained from pathology/clinical records and re-evaluated. Among 27 931 individuals (60% women), we found 728 incident CRC cases during 428 924 person-years of follow-up. Fibre intake was inversely associated with CRC risk (P(trend) = 0.026). Concerning colon cancer, we observed borderline interaction between fibre intake and sex (P = 0.052) and significant protective association restricted to women (P(trend) = 0.013). Intake of fruits and berries was inversely associated with colon cancer in women (P(trend) = 0.022). We also observed significant interactions between intakes of fibre (P = 0.048) and vegetables (P = 0.039) and sex on rectal cancer, but no significant associations were seen between intake of fibre, or its sources, in either of the sexes. Except for inverse associations between intake of fibre-rich cereal products and N0- and M0-tumours, we did not observe significant associations with different TNM stages. Our findings suggest different associations between fibre intake and CRC depending on sex, tumour site and fibre source. High fibre intake, especially from fruits and berries, may, above all, prevent tumour development in the colon in women. No clear differences by TNM classification were detected. PMID- 26281853 TI - Evaluating the effects of mindfulness-based interventions for informal palliative caregivers: A systematic literature review. AB - BACKGROUND: There is a need to identify proactive, evidence-based interventions to support informal palliative caregivers. Mindfulness-based interventions, evidenced in the literature as providing physical and mental health benefits for diverse populations, may have application in the setting of palliative caregiving. AIM: To describe, evaluate and synthesise the peer-reviewed literature on the effects of mindfulness-based interventions for informal palliative caregivers. DESIGN: A Systematic Literature Review according to the Preferred Reporting Items for Systematic Review and Meta Analyses guidelines and a Narrative synthesis. DATA SOURCES: The Cochrane Library, CINAHL, MEDLINE, PsycINFO and EMBASE databases, searched from inception to February 2014 and references of included studies. RESULTS: A total of 13 articles, reporting 10 studies (n = 432 participants) were included. All studies were conducted in the last 5 years. Dementia caregivers were the most frequently researched population (n = 7). Results suggest that mindfulness-based interventions are feasible and acceptable to offer to informal palliative caregivers and may provide benefit, particularly in terms of reducing depression and caregiver burden and increasing quality of life. However, effects were not as robust as findings in the wider mindfulness intervention literature. CONCLUSION: This is the first systematic literature review on this topic. Results suggest both feasibility and potential benefit. Further qualitative research is required to explore the outcomes identified by informal caregivers themselves as the reduced magnitude of effect may suggest that we are not measuring the right outcomes in this context. This would inform more sensitive outcome measures for future intervention studies and guide the development and application of mindfulness-based models in this area. PMID- 26281854 TI - A multimethod analysis of shared decision-making in hospice interdisciplinary team meetings including family caregivers. AB - BACKGROUND: Much of the existing research on shared decision-making in hospice and palliative care focuses on the provider-patient dyad; little is known about shared decision-making that is inclusive of family members of patients with advanced disease. AIM: We sought to describe shared decision-making as it occurred in hospice interdisciplinary team meetings that included family caregivers as participants using video-conferencing technology. DESIGN: We conducted a multimethod study in which we used content and thematic analysis techniques to analyze video-recordings of hospice interdisciplinary team meetings (n = 100), individual interviews of family caregivers (n = 73) and hospice staff members (n = 78), and research field notes. SETTING/PARTICIPANTS: Participants in the original studies from which data for this analysis were drawn were hospice family caregivers and staff members employed by one of five different community based hospice agencies located in the Midwestern United States. RESULTS: Shared decision-making occurred infrequently in hospice interdisciplinary team meetings that included family caregivers. Barriers to shared decision-making included time constraints, communication skill deficits, unaddressed emotional needs, staff absences, and unclear role expectations. The hospice philosophy of care, current trends in healthcare delivery, the interdisciplinary nature of hospice teams, and the designation of a team leader/facilitator supported shared decision-making. CONCLUSION: The involvement of family caregivers in hospice interdisciplinary team meetings using video-conferencing technology creates a useful platform for shared decision-making; however, steps must be taken to transform family caregivers from meeting attendees to shared decision-makers. PMID- 26281855 TI - Becoming a person with HIV: experiences of Cambodian women infected by their spouses. AB - We conducted an interpretive phenomenological investigation in order to understand, within a Cambodian sociocultural context, the lived experiences of women infected with HIV by their husbands as they navigated the tasks of discovering, disclosing and dealing with the diagnosis. Using an open-ended interview protocol and an interpretive phenomenological approach, data were analysed from 15 women (aged 28-42 years) who self-identified the HIV transmission as coming from their spouses. Using qualitative inductive analysis, we were able to identify three main themes: (1) finding oneself to be HIV positive, (2) encountering HIV--accepting an unwelcomed guest and (3) going public--dealing with the fear of discrimination. Participants consistently delayed testing for HIV and, after receiving an HIV-positive diagnosis, had to deal with painful emotions and discrimination within their social network. The complexity of gender roles and the sociocultural status of the women acted as behavioural determinants of their responses to HIV transmission from their spouses. PMID- 26281856 TI - Axenfeld-Rieger syndrome: a case report. AB - Axenfeld-Rieger syndrome (ARS) is a rare autosomal dominant condition manifesting as a heterogeneous group of features. Of particular note are the ocular and craniofacial anomalies and dental features such as hypodontia, microdontia, taurodontism, enamel hypoplasia, conical-shaped teeth, shortened roots and delayed eruption. To treat cases with ARS effectively, a multidisciplinary approach is required, and this report describes the complex and long-term management of a case with input from Paediatric Dentistry, Orthodontics, Restorative Dentistry, Speech and Language Therapy, Oral and Maxillofacial Surgery and Radiology. PMID- 26281857 TI - Acceptance and commitment group therapy (ACT-G) for health anxiety: a randomized controlled trial. AB - BACKGROUND: Severe health anxiety is frequent and costly, yet rarely diagnosed or treated. Earlier treatment studies show problems with recruitment, dropout and recovery. In the current study, the authors aimed to test the effect of acceptance and commitment group therapy (ACT-G) compared to waitlist in patients with severe health anxiety. METHOD: During March 2010 to April 2012, 126 consecutively referred patients meeting research criteria for severe health anxiety were block-randomized (1:1) to ACT-G or a 10 months' waitlist (Clinicaltrials.gov, no. NCT01158430). Patients allocated to ACT-G were treated in seven groups of nine patients between December 2010 and October 2012 and received nine weekly 3-h group sessions and a booster session consisting of ACT techniques. The primary outcome was decided a priori as the mean change in self reported illness worry on the Whiteley-7 Index (WI) from baseline to 10 months' follow-up. Secondary outcomes were improvement in emotional distress and health related quality of life at 10 months' follow-up. RESULTS: Intention-to-treat analysis showed a statistically significant mean difference of 20.5 points [95% confidence interval (CI) 11.7-29.4, p < 0.001] on the WI between the groups at 10 months, and the between-group effect sizes were large (Cohen's d = 0.89, 95% CI 0.50-1.29). The number needed to treat was 2.4 (95% CI 1.4-3.4, p < 0.001). Diagnosis and treatment were well accepted by the patients. CONCLUSIONS: ACT-G seems feasible, acceptable and effective in treating severe health anxiety. PMID- 26281860 TI - Risk of recurrence estimates with IHC4+C are tolerant of variations in staining and scoring: an analytical validity study. AB - AIMS: The IHC4+C score combines assessment of oestrogen receptor (ER), progesterone receptor (PgR), HER2 and Ki67 with clinicopathological parameters to identify the risk of distant disease recurrence in patients with breast cancer, so, aiding treatment decision-making on adjuvant chemotherapy. Despite low cost and wide availability, the reported use of IHC4+C remains limited; one explanation for this is the perception that immunohistochemistry (IHC)-based methods and assessment of them lack precision, reproducibility and portability. We examined the effects of decentralised testing and easily reproducible estimate based scoring methods on IHC4+C scores to determine its suitability for wider adoption. METHODS: Sections from a breast cancer tissue micro-array (TMA) were distributed to three centres undertaking diagnostic breast cancer IHC. Centres stained sections using their standard procedures, and returned them for central assessment. The results were compared with those obtained at IHC4+C's originating hospital (Royal Marsden Hospital (RMH)). In parallel, TMA sections stained at RMH were scored by a variety of simplified non-counting-based methods. The results were compared with those produced using counting. RESULTS: There was a high degree of correlation between individual IHC results produced by external centres and those of RMH (r: 0.797-0.982), and between risk of distant recurrence scores derived from them (r: 0.972-0.984). Scoring methods for ER and PgR could be adapted to require less precision without significantly affecting correlation with counted results (r: 0.933 and 0.980, respectively), but correlation between estimating and counting for Ki67 was poorer (r: 0.855). CONCLUSIONS: IHC4+C is tolerant of variation in staining and scoring methods. Although additional confirmatory comparative studies are required, these data support use of IHC4+C in clinical practice outside RMH. PMID- 26281861 TI - High Ki67 expression is an independent good prognostic marker in colorectal cancer. AB - AIMS: To correlate Ki67 expression with outcome in colorectal cancer (CRC). METHODS: Ki67 labelling index (Ki67LI) was analysed by immunohistochemistry on a tissue microarray containing 1800 CRCs. The results were compared with clinicopathological and molecular parameters. RESULTS: Ki67LI was considered low in 26.3%, moderate in 56.7% and high in 17.0% of 1653 interpretable CRCs. High Ki67 expression was associated with low tumour stage (p<0.0001) and nodal status (p=0.0315), but not with tumour grade (p=0.8639), histological tumour type (p=0.1542) or tumour localisation, and was an independent prognosticator of favourable survival (p=0.0121). High Ki67 expression was also significantly associated with high-level nuclear beta-catenin and p53 expression (p<0.0001 and p=0.0095, respectively). CONCLUSIONS: In summary, our data show that high Ki67 expression in CRCs is associated with good clinical outcome. Ki67, p53 and beta catenin overexpression seem to be linked to CRC, and indicate a cellular state of high proliferative activity. Finally, our findings strongly argue for a clinical utility of Ki67 immunostaining as an independent prognostic biomarker in CRC. PMID- 26281862 TI - Tissue factor is unregulated in microvascular endothelial cells of patients with heart failure. AB - AIMS: Several lines of evidence point to hypercoagulability as an important factor for heart failure (HF) pathogenesis. METHODS: We hypothesised that endothelial tissue factor (TF) expression reflects altered tissue haemostasis which is related to the severity of HF. Accordingly, we investigated TF expression in the biopsies of 60 patients with HF and 22 without HF. In addition, we assessed the relationship between endothelial TF expression and clinical markers of HF severity. RESULTS: The control subjects without HF presented absent or weak TF expression in few microvessels, while the endomyocardial biopsies of patients with HF, capillary vessels presented both weak and severe staining patterns by immunohistochemistry usually with regional distribution. This was collaborated by the immune electron microscopic study. The severe microvessel TF antigen expression was found in 11 (18.3%) patients with HF. The endothelial TF expression was inversely associated with left ventricular ejection fraction (r= 0.42, p=0.001) and positively with N-terminal brain natriuretic peptide (r=0.36, p<0.023), markers of HF severity. CONCLUSIONS: Regional upregulation of the TF in the capillary endothelial cells suggests local myocardial thrombogenicity. Furthermore, the relationship between endothelial TF and HF severity would be keeping in line with the hypothesis that an altered tissue haemostasis is most profoundly expressed in patients with severe HF. Weak TF expression found in several microvessels of the biopsy specimens patients without HF pathology might be potentially related to a low basal level of activation of the clotting system in normal individuals. PMID- 26281863 TI - An immunohistochemical comparison of two TTF-1 monoclonal antibodies in atypical squamous lesions and sarcomatoid carcinoma of the lung, and pleural malignant mesothelioma. AB - Immunohistochemical detection of thyroid transcription factor-1 (TTF-1) plays an important role in the diagnosis and subclassification of non-small cell carcinomas of the lung in biopsy and some cytology samples, specifically for identification of squamous cell carcinoma (classically negative) and non-mucinous adenocarcinoma (positive in most cases) and for discrimination between lung adenocarcinoma and pleural malignant mesothelioma (classically negative). AIMS AND METHODS: We carried out a comparison of the widely used mouse monoclonal TTF 1 antibody based on the 8G7G3/1 clone versus the more recently introduced rabbit monoclonal antibody (MAb) based on the SP141 clone. RESULTS: Both antibodies labelled alveolar epithelium in normal lung parenchyma, but the SP141 antibody also labelled bronchial mucosal basal cells. All 13 cases of atypical squamous lesions (including one case of bronchial squamous dysplasia) were negative with the 8G7G3/1 antibody, but 6/13 cases of squamous carcinoma/dysplasia showed positive nuclear labelling with the SP141 antibody in the same tissue biopsy. All 35 cases of adenocarcinoma of the lung were positive with both antibodies. For 12 cases of sarcomatoid carcinoma of the lung, two cases were labelled with the 8G7G3/1 antibody, whereas positive labelling of 4/12 cases was observed with SP141. All 66 cases of epithelioid malignant mesothelioma were negative with both antibodies, but 8/19 cases of sarcomatoid mesothelioma showed positive nuclear labelling with the SP141 antibody (0/19 with 8G7G3/1). CONCLUSIONS: Our findings indicate differences in the rates of positive and negative labelling with these two antibodies, and suggest the potential for misclassification of a proportion of squamous carcinomas of the lung as adenocarcinoma, and for misdiagnosis of some sarcomatoid mesotheliomas as sarcomatoid carcinoma of the lung. If the results of SP141 are assigned overriding significance, our findings further indicate that in isolation, neither negative labelling with either 8G7G3/1 or SP141 nor positive labelling with the SP141 MAb discriminates between sarcomatoid carcinoma and sarcomatoid mesothelioma, whereas positive labelling with the 8G7G3/1 MAb favours a diagnosis of sarcomatoid carcinoma. The literature suggests that these seemingly 'aberrant' results with the SP141 antibody are not 'false' positives, but rather real detection of low levels of TTF-1 protein in a broader range of tumours than is widely recognised. PMID- 26281865 TI - Li-O2 Kinetic Overpotentials: Tafel Plots from Experiment and First-Principles Theory. AB - We report the current dependence of the fundamental kinetic overpotentials for Li O2 discharge and charge (Tafel plots) that define the optimal cycle efficiency in a Li-air battery. Comparison of the unusual experimental Tafel plots obtained in a bulk electrolysis cell with those obtained by first-principles theory is semiquantitative. The kinetic overpotentials for any practical current density are very small, considerably less than polarization losses due to iR drops from the cell impedance in Li-O2 batteries. If only the kinetic overpotentials were present, then a discharge-charge voltaic cycle efficiency of ~85% should be possible at ~10 mA/cm(2) superficial current density in a battery of ~0.1 m(2) total cathode area. We therefore suggest that minimizing the cell impedance is a more important problem than minimizing the kinetic overpotentials to develop higher current Li-air batteries. PMID- 26281864 TI - Correlation between DPYD gene variation and KRAS wild type status in colorectal cancer. AB - AIMS: Failure and side effects of combined cytotoxic therapy are challenges in the treatment of metastatic colorectal cancer (CRC). DPYD gene variations can potentially predict toxicity to 5-fluorouracil (FU)-based therapy and KRAS-, NRAS , BRAF-, PIK3CA-wild type status is a known prerequisite for epidermal growth factor receptor (EGFR) inhibitor therapy. This study was performed to search for a possible link between these therapeutic markers. METHODS: The DPYD gene variations c.496A>G, c.1679T>G, c.2846A>T and KRAS/NRAS/BRAF/PIK3CA mutational status were determined in non-neoplastic, primary CRC and metastatic CRC tissue from 115 patients. RESULTS: The polymorphism c.496A>G was the DPYD gene variant with the highest detection rate (12.9%), occurred predominantly in females (86.7%, p=0.0044) and was exclusively seen in KRAS wild type primary CRC (15/65 (23.1%) vs 0/51 (0%) in KRAS-mutated primary CRC, respectively, p=0.0001). CONCLUSIONS: This genetic profile could define a patient group requiring alternative combined therapeutic approaches. Global testing of large patient cohorts is necessary to prove this concept. PMID- 26281866 TI - Exploration of Structures of Two-Dimensional Boron-Silicon Compounds with sp(2) Silicon. AB - The most stable structures of two-dimensional (2D) boron-silicon (B-Si) compounds containing planar sp(2)-bonding silicon (sp(2)-Si) are explored using the first principles calculation-based particle-swarm optimization method. Among 10 B-Si compounds considered, we find that for BSi4, BSi3, BSi, B2Si, B3Si, B5Si, and B6Si, each Si atom is bonded with three B or Si atoms within the same plane, representing a preference of planar sp(2)-Si structure in B-Si compounds. For BSi2 and B4Si, the predicted lowest-energy structures entail a small out-of-plane buckling. Furthermore, a planar-tetracoordinated Si (ptSi) atom bonded with four B atoms within the same plane is observed in the lowest-energy structure of B7Si compound. Dynamical stabilities of the predicted 10 2D B-Si compounds are confirmed via phonon-spectrum calculation. The lowest-energy 2D B-Si compounds are all metals, regardless of the B-Si stoichiometry considered in this study. PMID- 26281867 TI - A Noble-Metal-Free Hydrogen Evolution Catalyst Grafted to Visible Light-Absorbing Semiconductors. AB - We report a method for facile connection of a nickel bisdiphosphine-based functional mimic of the active site of hydrogenase to photocathodes that are relevant to artificial photosynthesis. This procedure exploits the UV-induced immobilization chemistry of alkenes to gallium phosphide and silicon surfaces. The photochemical grafting provides a means for patterning molecular linkers with attachment points to catalysts. Successful grafting is characterized by grazing angle attenuated total reflection Fourier transform infrared spectroscopy (GATR FTIR), which shows catalyst vibrational modes, as well as X-ray photoelectron spectroscopy (XPS), which confirms the presence of intact Ni complex on the surface. The modular nature of this approach allows independent modification of the light absorber, bridging material, anchoring functionality, or catalyst as new materials and discoveries emerge. PMID- 26281868 TI - How Crystals Nucleate and Grow in Aqueous NaCl Solution. AB - Large-scale molecular dynamics simulations (64 000 particles) are used to examine the microscopic mechanism of crystal nucleation and growth in a slightly supersaturated solution of NaCl in water at 300 K and 1 atm. Early-stage nucleation is observed, and the growth of a single crystal is followed for ~140 ns. It is shown that the nucleation and growth process is better described by Ostwald's rule of stages than by classical nucleation theory. Crystal nucleation originates in a region where the local salt concentration exceeds that of the bulk solution. The early-stage nucleus is a loosely ordered arrangement of ions that retains a significant amount of water. The residual water is slowly removed as the crystal grows and evolves toward its stable anhydrous state. PMID- 26281869 TI - On the Biexponential Decay of the Photoluminescence of the Two Crystallographically-Independent Molecules in Crystals of [Cu(I)(phen)(PPh3)2][BF4]. AB - [Cu(I)(phen)(PPh3)2][BF4] crystallizes with two nonsymmetry-related molecules in the asymmetric unit. Synchrotron time-resolved X-ray diffraction experiments have shown that the two independent molecules distort differently on MLCT excitation. The luminescence decay of the crystals is biexponential with two different Stokes shifts, the more rapid decay corresponding to the shorter wavelength emission. Its amplitude diminishes rapidly with an increase in temperature, indicating that this emission is not due to a thermal activation to a higher state. The double emission is attributed to the presence of two independent molecules with drastically different packing environments. It is concluded that the solid-state environment must be analyzed whenever photochemical properties of molecular solids are reported. PMID- 26281870 TI - Extremely Slow Dynamics of an Abiotic Helical Assembly: Unusual Relevance to the Secondary Structure of Proteins. AB - Serendipitously, we found that isoleucine methylester functionalized perylenediimide 1 undergoes an extremely slow supramolecular helical assembly over a day's time. Surprisingly, heating led to irreversible chiral denaturation. However, reversible helical assembly could be achieved only in the presence of nondenatured aggregates of 1, which act as seeds. The intriguing functional relevance deduced from 1 was employed to draw parallels with the secondary structure of proteins, envisaging its plausible implications. PMID- 26281871 TI - Single-Molecule Conductance in a Series of Extended Viologen Molecules. AB - Single-molecule conductance in a series of extended viologen molecules was measured at room temperature using a gold-molecule-gold scanning tunneling microscopy break junction arrangement. Conductance values for individual molecules change from 4.8 +/- 1.2 nS for the shortest compound to 2.9 +/- 1.0 nS for the compound with six repeating units and length of 11 nm. The latter value is almost 3 orders of magnitude higher than that reported for all-carbon-based aromatic molecular wires of comparable length. On the basis of the length of the molecules, an attenuation factor of only 0.06 +/- 0.004 nm(-1) (0.006 +/- 0.0004 A(-1)) was obtained. To the best of our knowledge, this is the smallest value reported for the conductance attenuation in a series of molecular wires. PMID- 26281872 TI - Ultrafast Photochemistry of a Manganese-Tricarbonyl CO-Releasing Molecule (CORM) in Aqueous Solution. AB - Ultraviolet irradiation of a manganese-tricarbonyl CO-releasing molecule (CORM) in water eventually leads to the liberation of some of the carbon monoxide ligands. By ultraviolet pump/mid-infrared probe femtosecond transient absorption spectroscopy in combination with quantum chemical calculations, we could disclose for the exemplary compound [Mn(CO)3(tpm)](+) (tpm = tris(2-pyrazolyl)methane) that only one of the three carbonyl ligands is photochemically dissociated on an ultrafast time scale and that some molecules may undergo geminate recombination. PMID- 26281873 TI - Correction to "Unraveling the Complex Nature of the Hydrated Electron". PMID- 26281874 TI - Supercharged Low-Temperature Oxygen Storage Capacity of Ceria at the Nanoscale. AB - We provide an explanation for the experimental finding of a dramatically enhanced low-temperature oxygen storage capacity for small ceria nanoparticles. At low temperature, small octahedral ceria nanoparticles will be understoichiometric at both oxidizing and reducing conditions without showing explicit oxygen vacancies. Instead, rather than becoming stoichiometric at oxidizing conditions, such particles are stabilized through oxygen adsorption forming superoxo (O2(-)) ions and become in this way supercharged with oxygen. The supercharging effect is size dependent and largest for small nanoparticles where it gives a direct increase in the oxygen storage capacity and simultaneously provides a source of active oxygen species at low temperatures. PMID- 26281875 TI - Cryogenic Single-Nanocrystal Spectroscopy: Reading the Spectral Fingerprint of Individual CdSe Quantum Dots. AB - Spectroscopically resolved emission from single nanocrystals at cryogenic temperatures provides unique insight into physical processes that occur within these materials. At low temperatures, the emission spectra collapse to narrow lines, revealing a rich spectroscopic landscape and unexpected properties, completely hidden at the ensemble level. Since these techniques were first used, the technology of nanocrystal synthesis has matured significantly, and new materials with outstanding photostability have been reported. In this perspective, we show how cryogenic spectroscopy of single nanocrystals probes the fundamental excitonic structure of the band edge, revealing spectral fingerprints that are highly sensitive to a range of photophysical properties as well as nanocrystal morphology. In particular, spectral and temporal signatures of biexciton and trion emission are revealed, and their relevance to emerging technologies is discussed. Overall we show how cryogenic single nanocrystal spectroscopy can be used as a tool for understanding fundamental photophysics and guiding the synthesis of new nanocrystal materials. PMID- 26281876 TI - Molecular Density Functional Theory of Water. AB - Three-dimensional implementations of liquid-state theories offer an efficient alternative to computer simulations for the atomic-level description of aqueous solutions in complex environments. In this context, we present a (classical) molecular density functional theory (MDFT) of water that is derived from first principles and is based on two classical density fields, a scalar one, the particle density, and a vectorial one, the multipolar polarization density. Its implementation requires as input the partial charge distribution of a water molecule and three measurable bulk properties, namely, the structure factor and the k-dependent longitudinal and transverse dielectric constants. It has to be complemented by a solute-solvent three-body term that reinforces tetrahedral order at short-range. The approach is shown to provide the correct 3-D microscopic solvation profile around various molecular solutes, possibly possessing H-bonding sites, at a computer cost two to three orders of magnitude lower than with explicit simulations. PMID- 26281877 TI - The Complex Interaction of Spectroscopic Shifts and Electronic Properties in Semiconductor Nanocrystal Films. AB - Absorption spectroscopy has traditionally served as a powerful technique for the study of solution synthesized semiconductor nanocrystals, enabling information on the size, dispersity, concentration, and overall quality of a sample to be obtained quickly and easily. When thin, densely packed films of these materials are produced through ligand exchange, spectroscopic shifts to both higher and lower energy are observed. Reduction of the internanocrystal distance can result in both a change to the overall dielectric constant of the film as well as increased electronic coupling, producing a redshift. At the same time, surface oxidation has the effect of increasing the confinement, producing a blueshift. This Perspective focuses on PbSe, a material of current interest, and the potential for correlating these spectroscopic shifts to optoelectronic properties, highlighting both recent work in the literature and areas in need of additional study. PMID- 26281878 TI - Correction to "Electron at the Surface of Water: Dehydrated or Not?". PMID- 26281879 TI - Optical Properties of Strongly Coupled Quantum Dot-Ligand Systems. AB - This Perspective describes the mechanisms by which organic surfactants, in particular, phenyldithiocarbamates (PTCs), couple electronically to the delocalized states of semiconductor quantum dots (QDs). This coupling reduces the confinement energies of excitonic carriers and, in the case of PTC, the optical band gap of metal chalcogenide QDs by up to 1 eV by selectively delocalizing the excitonic hole. The reduction of confinement energy for the hole is enabled by the creation of interfacial electronic states near the valence band edge of the QD. The PTC case illuminates the general minimal requirements for surfactants to achieve observable bathochromic or hypsochromic shifts of the optical band gap of QDs; these include frontier orbitals with energies near the relevant semiconductor band edge, the correct symmetry to mix with the orbitals of the relevant band, and an adsorption geometry that permits spatial overlap between the orbitals of the ligand and those of the relevant band (Se 4p orbitals for CdSe, for example). The shift is enhanced by energetic resonance of frontier orbitals of the surfactant with a high density of states region of the band, which, for CdSe, is ~1 eV below the band edge. The Perspective discusses other examples of strong-coupling surfactants and compares the orbital mixing mechanism with other mechanisms of surfactant-induced shifts in the QD band gap. PMID- 26281880 TI - Alternating Plasmonic Nanoparticle Heterochains Made by Polymerase Chain Reaction and Their Optical Properties. AB - Organization of nanoparticles (NPs) of different materials into superstructures of higher complexity represents a key challenge in nanotechnology. Polymerase chain reaction (PCR) was used in this study to fabricate chains consisting of plasmonic NPs of different sizes, thus denoted heterochains. The NPs in such chains are connected by DNA oligomers, alternating in a sequence big-small-big small-... and spanning lengths in the range of 40-300 nm by varying the number of PCR cycles. They display strong plasmonic chirality at 500-600 nm, the chiral activity revealing nonmonotonous dependence on the length of heterochains. We find the strength of surface-enhanced Raman scattering (SERS) to increase with chain length, while the chiral response initially increased and then decreased with the number of PCR cycles. The relationship between the optical properties of the heterochains and their structure/length is discussed. The length-dependent intense optical response of the plasmonic NP heterochains holds great potential for biosensing applications. PMID- 26281881 TI - Attractive Forces between Charged Colloidal Particles Induced by Multivalent Ions Revealed by Confronting Aggregation and Direct Force Measurements. AB - Interactions involving charged particles in the presence of multivalent ions are relevant in wide-range of phenomena, including condensation of nucleic acids, cement hardening, or water treatment. Here, we study such interactions by combining direct force measurements with atomic force microscopy (AFM) and aggregation studies with time-resolved light scattering for particles originating from the same colloidal suspension for the first time. Classical DLVO theory is found to be only applicable for monovalent and divalent ions. For ions of higher valence, charge inversion and additional non-DLVO attractive forces are observed. These attractive forces can be attributed to surface charge heterogeneities, which leads to stability ratios that are calculated from direct force measurements to be higher than the experimental ones. Ion-ion correlations are equally important as they induce the charge inversion in the presence of trivalent or tetravalent ions, and they enhance the surface charge heterogeneities. Such heterogeneities therefore play an essential role in controlling interactions in particle suspensions containing multivalent ions. PMID- 26281882 TI - Molecular Chemistry to the Fore: New Insights into the Fascinating World of Photoactive Colloidal Semiconductor Nanocrystals. AB - Colloidal semiconductor nanocrystals possess unique properties that are unmatched by other chromophores such as organic dyes or transition-metal complexes. These versatile building blocks have generated much scientific interest and found applications in bioimaging, tracking, lighting, lasing, photovoltaics, photocatalysis, thermoelectrics, and spintronics. Despite these advances, important challenges remain, notably how to produce semiconductor nanostructures with predetermined architecture, how to produce metastable semiconductor nanostructures that are hard to isolate by conventional syntheses, and how to control the degree of surface loading or valence per nanocrystal. Molecular chemists are very familiar with these issues and can use their expertise to help solve these challenges. In this Perspective, we present our group's recent work on bottom-up molecular control of nanoscale composition and morphology, low temperature photochemical routes to semiconductor heterostructures and metastable phases, solar-to-chemical energy conversion with semiconductor-based photocatalysts, and controlled surface modification of colloidal semiconductors that bypasses ligand exchange. PMID- 26281883 TI - In Situ Raman Spectroscopic Study of Gypsum (CaSO4.2H2O) and Epsomite (MgSO4.7H2O) Dehydration Utilizing an Ultrasonic Levitator. AB - We present an original apparatus combining an acoustic levitator and a pressure compatible process chamber. To characterize in situ the chemical and physical modifications of a levitated, single particle while heated to well-defined temperatures using a carbon dioxide laser, the chamber is interfaced to a Raman spectroscopic probe. As a proof-of-concept study, by gradually increasing the heating temperature, we observed the variations in the Raman spectra as 150 MUg of crystals of gypsum and epsomite were dehydrated in anhydrous nitrogen gas. We display spectra showing the decreasing intensities of the nu1 symmetric and nu3 asymmetric stretching modes of water with time and the simultaneous shift of the nu1(SO4(2-)) symmetric stretch mode to higher wavenumbers. Our results demonstrate that the new apparatus is well suited to study the dehydration of levitated species such as minerals and offers potential advantages compared with previous experiments on bulk samples. PMID- 26281884 TI - Defect-Electron Spreading on the TiO2(110) Semiconductor Surface by Water Adsorption. AB - The dissociative adsorption of water at oxygen-vacancy defect sites on the TiO2(110) surface spatially redistributes the defect electron density originally present at subsurface sites near the defect sites. This redistribution of defect electrons makes them more accessible to Ti(4+) ions surrounding the defects. The redistribution of electron density decreases the O(+) desorption yield from surface lattice O(2-) ions in TiO2, as excited by electron-stimulated desorption (ESD). A model in which OH formation on defect sites redistributes defect electrons to neighboring Ti(4+) sites is proposed. This switches off the Knotek Feibelman mechanism for ESD of O(+) ions from lattice sites. Conversely, enhanced O(+) reneutralization could also be induced by redistribution of defect electrons. The redistribution of surface electrons by adsorption is further verified by the use of donor and acceptor molecules that add or remove electron density. PMID- 26281885 TI - Colloidal Quantum Dots: A Model Nanoscience System. PMID- 26281886 TI - Nanoherding: Plasma-Chemical Synthesis and Electric-Charge-Driven Self Organization of SiO2 Nanodots. AB - We report on the chemical synthesis of the arrays of silicon oxide nanodots and their self-organization on the surface via physical processes triggered by surface charges. The method based on chemically active oxygen plasma leads to the rearrangement of nanostructures and eventually to the formation of groups of nanodots. This behavior is explained in terms of the effect of electric field on the kinetics of surface processes. The direct measurements of the electric charges on the surface demonstrate that the charge correlates with the density and arrangement of nanodots within the array. Extensive numerical simulations support the proposed mechanism and prove a critical role of the electric charges in the self-organization. This simple and environment-friendly self-guided process could be used in the chemical synthesis of large arrays of nanodots on semiconducting surfaces for a variety of applications in catalysis, energy conversion and storage, photochemistry, environmental and biosensing, and several others. PMID- 26281887 TI - Fracking: What Can Physical Chemistry Offer? PMID- 26281888 TI - Indirect Exciton Formation due to Inhibited Carrier Thermalization in Single CdSe/CdS Nanocrystals. AB - Temperature-dependent single-particle spectroscopy is used to study interfacial energy transfer in model light-harvesting CdSe/CdS core-shell tetrapod nanocrystals. Using alternating excitation energies, we identify two thermalized exciton states in single nanoparticles that are attributed to a strain-induced interfacial barrier. At cryogenic temperatures, emission from both states exemplifies the effects of intraparticle disorder and enables their simultaneous characterization, revealing that the two states are distinct in regards to emission polarization, spectral diffusion, and blinking. PMID- 26281889 TI - Critical Materials Recovery from Solutions and Wastes: Retrospective and Outlook. PMID- 26281890 TI - Increasing Boiling Heat Transfer using Low Conductivity Materials. AB - We report the counterintuitive mechanism of increasing boiling heat transfer by incorporating low-conductivity materials at the interface between the surface and fluid. By embedding an array of non-conductive lines into a high-conductivity substrate, in-plane variations in the local surface temperature are created. During boiling the surface temperature varies spatially across the substrate, alternating between high and low values, and promotes the organization of distinct liquid and vapor flows. By systematically tuning the peak-to-peak wavelength of this spatial temperature variation, a resonance-like effect is seen at a value equal to the capillary length of the fluid. Replacing ~18% of the surface with a non-conductive epoxy results in a greater than 5x increase in heat transfer rate at a given superheat temperature. This drastic and counterintuitive increase is shown to be due to optimized bubble dynamics, where ordered pathways allow for efficient removal of vapor and the return of replenishing liquid. The use of engineered thermal gradients represents a potentially disruptive approach to create high-efficiency and high-heat-flux boiling surfaces which are naturally insensitive to fouling and degradation as compared to other approaches. PMID- 26281891 TI - CaMKII regulates the strength of the epithelial barrier. AB - Epithelial cells define the boundary between the outside and the inside of our body by constructing the diffusion barrier. Tight junctions (TJs) of epithelial cells function as barriers against invasion of harmful microorganisms into the human body and free diffusion of water or ions from the body. Therefore, formation of TJs has to be strictly controlled in epithelial cells. However, the molecular mechanisms governing this regulation are largely unknown. In this study, we identified Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) as a regulator of the barrier function of TJs. CaMKII inhibition led to enlargement of TJ-areas and up-regulation of the barrier function. CaMKII inhibition induced excess TJ formation in part by the activation of AMP-activated protein kinase (AMPK) and subsequent phosphorylation of claudin-1. As up-regulation of epithelial barriers is essential for the prevention of chronic inflammatory diseases, the identification of CaMKII as a modulator of TJ function paves the way for the development of new drugs to treat these diseases. PMID- 26281893 TI - Obesity: Older age and high BMI are associated with increased risk of loss of kidney function. PMID- 26281894 TI - Transplantation: Optimizing ECD graft outcomes. PMID- 26281892 TI - Kidney-brain crosstalk in the acute and chronic setting. AB - Patients with kidney disease often exhibit multiple organ dysfunction that is caused, in part, by marked connectivity between the kidney and other organs and tissues. Substantial crosstalk occurs between the kidney and the brain, as indicated by the frequent presentation of neurological disorders, such as cerebrovascular disease, cognitive impairment, and neuropathy during the natural history of chronic kidney disease. The underlying pathophysiology of such comorbid neurological disorders in kidney disease is governed by shared anatomic and vasoregulatory systems and humoral and non-humoral bidirectional pathways that affect both the kidney and the brain. During acute kidney injury, the brain and kidney might interact through the amplification of cytokine-induced damage, extravasation of leukocytes, oxidative stress, and dysregulation of sodium, potassium, and water channels. The advent of dialysis and renal transplantation programmes has led to a reduction in the rate of neurological complications associated with uraemia, but a new set of complications have arisen as a consequence of the effects of dialysis on the central nervous system over the short and long term. This Review discusses the clinical complications of acute and chronic renal failure from a neurologic perspective, and highlights current understanding of the underlying pathophysiologies. PMID- 26281899 TI - [Measurement of disease severity in dermatology]. AB - In order to determine the appropriate therapy for dermatological diseases, numerous measurement instruments are available to measure disease severity. Due to the lack of laboratory parameters for some dermatological diseases to objectify the disease severity (e.g., atopic dermatitis, psoriasis), questionnaires are used. Laboratory as well as questionnaire-based measurements should be reliable, valid, and sensitive to change. In addition, measurement instruments should be feasible. Classifications of disease severity which are based on inadequate measurement properties result in incorrect clinical decisions and limit evidence-based healthcare. Therefore, systematically developed and evidence-based recommendations for the use of individual measurement instruments should be taken into consideration. PMID- 26281900 TI - Vertical scapular osteotomy in congenital high scapula. AB - PURPOSE: Children with congenital high scapula (CHS) have a cosmetic and functional problem due to limited shoulder abduction. Treatment options include excision of the prominent superior angle, scapular relocation procedures and subtotal scapulectomy. Excision of the superomedial angle results only in cosmetic improvement. Subtotal scapulectomy and relocation procedures are associated with ugly scars, extensive bleeding and high incidence of brachial plexus injuries. Vertical scapular osteotomy (VSO) is another surgical option that provides cosmetic and functional improvement. The aim of this study is to assess medium to long term results of VSO in treatment of CHS. METHODS: This is a prospective case series study. Seven children with CHS were treated at our unit. Age ranged from 5-13 years with an average of 8.4 years. All children were females with unilateral affection. All children underwent a VSO as described by Campbell. We used the Cavendish grading system together with combined shoulder abduction for assessment. Follow up averaged 4.6 years. RESULTS: All children and parents were extremely satisfied with the results of surgery. All patients experienced an improvement in global shoulder abduction with an average gain in abduction of 52.9 degrees . All patients experienced an improvement in cosmetic appearance with better shoulder levelling. The Cavendish grade improved in all patients. CONCLUSION: This study emphasizes the results of previous authors demonstrating that CHS can be treated successfully with a VSO. The procedure is simple and its results are reproducible. PMID- 26281898 TI - A Lentiviral Vector Allowing Physiologically Regulated Membrane-anchored and Secreted Antibody Expression Depending on B-cell Maturation Status. AB - The development of lentiviral vectors (LVs) for expression of a specific antibody can be achieved through the transduction of mature B-cells. This approach would provide a versatile tool for active immunotherapy strategies for infectious diseases or cancer, as well as for protein engineering. Here, we created a lentiviral expression system mimicking the natural production of these two distinct immunoglobulin isoforms. We designed a LV (FAM2-LV) expressing an anti HCV-E2 surface glycoprotein antibody (AR3A) as a membrane-anchored Ig form or a soluble Ig form, depending on the B-cell maturation status. FAM2-LV induced high level and functional membrane expression of the transgenic antibody in a nonsecretory B-cell line. In contrast, a plasma cell (PC) line transduced with FAM2-LV preferentially produced the secreted transgenic antibody. Similar results were obtained with primary B-cells transduced ex vivo. Most importantly, FAM2-LV transduced primary B-cells efficiently differentiated into PCs, which secreted the neutralizing anti-HCV E2 antibody upon adoptive transfer into immunodeficient NSG (NOD/SCIDgammac(-/-)) recipient mice. Altogether, these results demonstrate that the conditional FAM2-LV allows preferential expression of the membrane anchored form of an antiviral neutralizing antibody in B-cells and permits secretion of a soluble antibody following B-cell maturation into PCs in vivo. PMID- 26281895 TI - Genetic, environmental, and epigenetic factors involved in CAKUT. AB - Congenital anomalies of the kidney and urinary tract (CAKUT) refer to a spectrum of structural renal malformations and are the leading cause of end-stage renal disease in children. The genetic diagnosis of CAKUT has proven to be challenging due to genetic and phenotypic heterogeneity and incomplete genetic penetrance. Monogenic causes of CAKUT have been identified using different approaches, including single gene screening, and gene panel and whole exome sequencing. The majority of the identified mutations, however, lack substantial evidence to support a pathogenic role in CAKUT. Copy number variants or single nucleotide variants that are associated with CAKUT have also been identified. Numerous studies support the influence of epigenetic and environmental factors on kidney development and the natural history of CAKUT, suggesting that the pathogenesis of this syndrome is multifactorial. In this Review we describe the current knowledge regarding the genetic susceptibility underlying CAKUT and the approaches used to investigate the genetic basis of CAKUT. We outline the associated environmental risk factors and epigenetic influences on CAKUT and discuss the challenges and strategies used to fully address the involvement and interplay of these factors in the pathogenesis of the disease. PMID- 26281901 TI - Cell-based assay system for high-throughput screening of anti-photo-aging agents in fibroblast transfectants. AB - The matricellular protein CCN1 is significantly elevated in acutely ultraviolet irradiated human skin and negatively regulates collagen homeostasis by suppressing collagen synthesis and increasing collagen degradation. In this study, we established a stable cell line, termed CCN1-GFs, by transfection of the pAcGFP1-1-CCN1 promoter plasmid and examined its usefulness as a cell-based assay system for screening anti-aging ingredients. The promoter of the reporter plasmid pAcGFP1-1-CCN1 promoter was transfected into NIH3T3 cells using the Lipofectamine reagent. G418-resistant cells were selected and further cloned. To confirm whether AcGFP1-1-CCN1 promoter plasmid recombined in the NIH3T3 cells, the level of AcGFP1-1-CCN1 was measured by PCR analysis. To determine if NIH3T3 cells expressed the gene encoding green fluorescence protein in a CCN1 promoter dependent manner, the reporter enzyme activities were assayed using a fluorimeter and flow cytometer. To determine if CCN1 inhibitor, which was selected through this system, exerted a direct effect on the downstream signal, mRNA expression of collagen1 and MMP1A was checked by using real-time PCR. UVB irradiation of CCN1 GFs resulted in increased CCN1 promoter activity. Treatment with retinoic acid, a CCN1 inhibitor, inhibited UV-induced CCN1 promoter activity. Subsequent use of this assay system to screen anti-aging ingredients revealed that CCN1-GFs treated with sclareol showed decreased levels of UVB-induced CCN1 expression. Sclareol attenuated UVB-induced photo-aging by an increase in collagen synthesis and decrease in MMP-1 activity. PMID- 26281902 TI - Small Sample Research: Considerations Beyond Statistical Power. AB - Small sample research presents a challenge to current standards of design and analytic approaches and the underlying notions of what constitutes good prevention science. Yet, small sample research is critically important as the research questions posed in small samples often represent serious health concerns in vulnerable and underrepresented populations. This commentary considers the Special Section on small sample research and also highlights additional challenges that arise in small sample research not considered in the Special Section, including generalizability, determining what constitutes knowledge, and ensuring that research designs match community desires. It also points to opportunities afforded by small sample research, such as a focus on and increased understanding of context and the emphasis it may place on alternatives to the randomized clinical trial. The commentary urges the development and adoption of innovative strategies to conduct research with small samples. PMID- 26281904 TI - Erratum to: Early laparoscopic cholecystectomy is superior to delayed acute cholecystitis: a meta-analysis of case-control studies. PMID- 26281903 TI - Clinical safety and outcomes of laparoscopic surgery versus open surgery for palliative resection of primary tumors in patients with stage IV colorectal cancer: a meta-analysis. AB - BACKGROUND: This study was performed to compare the clinical safety and outcomes of laparoscopic versus open surgery for primary tumors in patients with stage IV colorectal cancer. METHODS: Pertinent studies were selected from the MEDLINE, EMBASE, and Cochrane Library databases; references from published articles; and reviews. Both prospective and retrospective studies were included for the meta analysis. Clinical outcomes included safety, complications, mortality, and survival. RESULTS: Six trials involving 1802 patients were included. The operative time was longer for laparoscopic than for open surgery (mean difference (MD) = 44.20, 95 % confidence interval (CI) 17.31-71.09, Z = 3.22, P = 0.001). Laparoscopic surgery was also associated with fewer postoperative complications (odds ratio 0.53, 95 % CI 0.37-0.78, Z = 3.29, P = 0.001) and less operative blood loss (MD = -65.40, 95 % CI -102.37 to -28.42, Z = 3.47, P = 0.0005). Median survival ranged from 11.4 to 30.1 months. The total hospital stay was 1.68 days shorter for laparoscopic than for open surgery (95 % CI -1.83 to -1.53, Z = 21.64, P < 0.00001). CONCLUSION: Laparoscopic surgery for palliative resection of stage IV colorectal cancer is associated with better perioperative outcomes than open surgery. PMID- 26281906 TI - A foreign body in the nasopharynx: missing tooth mystery solved. PMID- 26281905 TI - Twenty-year experience with laparoscopic and retroperitoneoscopic nephrectomy in children: considerations and details of technique. AB - BACKGROUND: Nephrectomy is probably the most common urological indication for minimally invasive surgery (MIS) in children. The authors reported their experience in laparoscopic and retroperitoneoscopic nephrectomy analyzing their 20 years of experience in this procedure. METHODS: In a 20-year period (1995 2015), the authors performed 149 nephrectomies in children using MIS (87 left, 62 right). One hundred and one nephrectomies were performed using laparoscopy (LN) and 48 using retroperitoneoscopy (RN). Patients included 90 girls and 59 boys (average age 5.7 years). All the removed kidneys were nonfunctioning because of benign diseases: VUR (84), UPJO (38), MKDK (20), xanthogranulomatosis pyelonephritis (4), nephropathy causing uncontrollable hypertension (2) and nephrolithiasis (1). RESULTS: We had no conversion in laparoscopy. As for RN, we had 2 conversions to laparoscopy at the beginning of experience due to peritoneal opening. Operative time varied from 30 to 130 min in laparoscopy (average 47 min) and from 60 to 150 min (average 78 min) in retroperitoneoscopy. We recorded 8 complications (5.3 %): 3 small bleedings (2 RN, 1 LN) during dissection, 2 peritoneal perforations during RN requiring conversion in LN, 1 abdominal abscess in case of xanthogranulomatosis pyelonephritis after LN requiring a redo surgery to drain the abscess, 1 instrumentation failure (LN) and 1 refluxing ureteral stump after RN requiring a redo surgery to remove it. CONCLUSIONS: LN is easier and faster to perform compared to RN. Complication rate was higher after RN compared to LN. In case of xanthogranulomatous pyelonephritis or other kidney infections or in case of previous renal surgery, retroperitoneoscopy is contraindicated. In case of VUR, LN is preferable to RN because it is fundamental to remove all the ureter. On the basis of our 20-year experience, we clearly prefer to perform nephrectomy using laparoscopy rather than retroperitoneoscopy leaving the indication to adopt RN only for the rare cases of MKDK. PMID- 26281908 TI - Can Cochrane Reviews inform decisions to improve indigenous people's health? PMID- 26281907 TI - A phase I open-label trial evaluating the cardiovascular safety of regorafenib in patients with advanced cancer. AB - PURPOSE: To characterize the cardiovascular safety profile of regorafenib in patients with advanced cancer. METHODS: Patients received regorafenib 160 mg/day for 21 days followed by a 7-day break. The primary endpoint was the change from baseline in QTcF at the regorafenib t(max) (Day 21, Cycle 1 or 2) and changes in left ventricular ejection fraction (LVEF) from baseline on Cycle 2, Day 21. Secondary objectives were pharmacokinetics, safety, anti-tumor activity and effects on electrocardiogram intervals. QT intervals were corrected using the methods of Fridericia (QTcF) and Bazett (QTcB). LVEF was assessed by multigated acquisition scanning. RESULTS: Fifty-three patients were enrolled, and all received at least one dose of regorafenib 160 mg. Twenty-five patients received regorafenib for 21 days without dose reduction. The mean change from baseline in QTcF at t(max) was (-)2 ms (90 % CI -8, 3). No patient experienced a change from baseline in QTcF > 60 ms, and two had QTcF changes between 30 and 60 ms. No patient had a QTcF or QTcB > 480 ms. In 27 patients who received at least 80 mg of regorafenib, the mean change from baseline in LVEF% +/- SD was 1.7 +/- 7.8. In 14 patients without a dose reduction, the mean change from baseline in LVEF% was (-)0.1 +/- 8.6 at Cycle 2, Day 21. Four patients experienced a LVEF decrease between 10 and 20 %. CONCLUSION: The effects of regorafenib on the QT/QTc interval and LVEF were modest and unlikely to be of clinical significance in the setting of advanced cancer therapy. PMID- 26281909 TI - Improving health outcomes for indigenous peoples: What are the challenges? PMID- 26281911 TI - Perspectives in the Medicinal Chemistry. PMID- 26281910 TI - Associations between dietary intakes of first-time fathers and their 20-month-old children are moderated by fathers' BMI, education and age. AB - Children's learning about food is considerable during their formative years, with parental influence being pivotal. Research has focused predominantly on maternal influences, with little known about the relationships between fathers' and children's diets. Greater understanding of this relationship is necessary for the design of appropriate interventions. The aim of this study was to investigate the associations between the diets of fathers and their children and the moderating effects of fathers' BMI, education and age on these associations. The diets of fathers and their first-born children (n 317) in the Melbourne Infant Feeding Activity and Nutrition Trial (InFANT) Program were assessed using an FFQ and 3 * 24-h recalls, respectively. The InFANT Program is a cluster-randomised controlled trial in the setting of first-time parents groups in Victoria, Australia. Associations between father and child fruit, vegetable, non-core food and non core drink intakes were assessed using linear regression. The extent to which these associations were mediated by maternal intake was tested. Moderation of associations by paternal BMI, education and age was assessed. Positive associations were found between fathers' and children's intake of fruit, sweet snacks and take-away foods. Paternal BMI, education and age moderated the relationships found for the intakes of fruit (BMI), vegetables (age), savoury snacks (BMI and education) and take-away foods (BMI and education). Our findings suggest that associations exist at a young age and are moderated by paternal BMI, education and age. This study highlights the importance of fathers in modelling healthy diets for their children. PMID- 26281912 TI - Current Progress in the Development of Metalloprotein Inhibitors. PMID- 26281913 TI - Fluid intelligence and executive functioning more alike than different? AB - OBJECTIVE: Fluid intelligence (Gf) has been related to executive functioning (EF) in previous studies, and it is also known to be correlated with crystallized intelligence (Gc). The present study includes representative measures of Gf, Gc, and EF frequently used in clinical practice to examine this Gf-EF relation. It is hypothesised that the Gf-EF relation is higher than the Gc-EF relation, and that working memory in particular (as a measure of EF) shows a high contribution to this relation. METHOD: Confirmatory factor analysis was performed on a mixed neuropsychiatric and non-clinical sample consisting of 188 participants, using the Kaufman Adolescent and Adult Intelligence Test, and three executive tasks of the Cambridge Neuropsychological Test Automated Battery, covering working memory, planning skills, and set shifting. RESULTS: The model fitted the data well [chi2(24)=35.25, p=0.07, RMSEA=0.050]. A very high correlation between Gf and EF was found (0.91), with working memory being the most profound indicator. A moderate to high correlation between Gc and EF was present. Current results are consistent with findings of a strong relation between Gf and working memory. CONCLUSION: Gf and EF are highly correlated. Gf dysfunction in neuropsychiatric patients warrants further EF examination and vice versa. It is discussed that results confirm the need to distinguish between specific versus general fluid/executive functioning, the latter being more involved when task complexity and novelty increase. This distinction can provide a more refined differential diagnosis and improve neuropsychiatric treatment indication. PMID- 26281914 TI - A hazard of lingual orthodontic attachments: a case report. AB - A case is presented of an unusual trauma to the floor of mouth caused by an unused lingual orthodontic button. This resulted in a vein being stripped from the floor of mouth and was associated with severe pain and restricted tongue movement. Management was by ligation and excision of the loop of the vessel under local anaesthesia. PMID- 26281915 TI - Effects of sodium methyldithiocarbamate on selected parameters of innate immunity and clearance of bacteria in a mouse model of sepsis. AB - AIMS: Sodium methyldithiocarbamate (SMD), the third most widely used conventional pesticide in the United States, has been reported to inhibit several parameters associated with inflammation and to decrease resistance to infection. In a previous study, survival time was markedly decreased when mice were treated orally with SMD shortly before challenge with a high dose of Escherichia coli (E. coli) that was lethal to most of the control mice. In the present study, we evaluated selected parameters of the innate immune system using a lower challenge dose of E. coli, to determine which (if any) of these parameters reflected continued changes through 24h. MAIN METHODS: Bacterial clearance from the peritoneal cavity, production of chemokines and cytokines, and body temperature were measured. KEY FINDINGS: All these parameters were reduced by SMD up to 12h after bacterial challenge, but the concentration of the anti-inflammatory cytokine IL-10 was increased. Even so, mice in the control and SMD-treated groups cleared most bacteria by 24h. Other parameters (cytokine concentrations and body temperature) were also normal or near normal by 24h. The same dosage of SMD administered intranasally also did not significantly decrease survival. Hypothermia from 16 to 28 h correlated with lethal outcome, but SMD significantly increased hypothermia only at 2 and 4h after challenge. SIGNIFICANCE: In spite of substantial early inhibition by SMD of parameters known to be important for resistance to infection, bacterial clearance and survival were not altered, suggesting immunological reserve and/or rapid recovery after transient effects of SMD. PMID- 26281916 TI - Y chromosome DNA in cervicovaginal self-collected samples of childbearing age women: Implications for epitheliotropic sexually transmitted infections? AB - AIMS: Assuming a possible association between Y chromosome (Yc)-DNA and sexually transmitted infection (STI) transmission rate, could Yc-DNA be related to an increased prevalence of Human Papillomavirus (HPV), Herpes Simplex Virus (HSV 1/2) and Chlamydia trachomatis (CT)? Could Yc-DNA be used to validate self reported condom use and sexual behaviors? MAIN METHODS: Cervicovaginal (CV) self collected samples of 612 Portuguese women at childbearing age were tested for Yc, HPV, HSV-1/2 and CT by polymerase chain reaction (PCR). KEY FINDINGS: The prevalence of Yc, HPV, CT and HSV-2 was 4.9%, 17.6%, 11.6% and 2.8%, respectively. There was a statistically significant trend for increased Yc-DNA prevalence in HPV positive samples [odds ratio (OR) 2.35, 95% confidence interval (CI) 1.03-5.31] and oral contraceptive (OC) use (OR 4.73, 95% CI 1.09-20.44). A protective effect of condom use was observed in Yc-DNA detection (OR 0.40, 95% CI 0.18-0.89). No statistically significant difference was found between Yc-DNA, CT and HSV-2 infection. HPV infection risk increased with age (>20 years), young age at first sexual intercourse (FSI) (<=18 years), >1 lifetime sexual partner (LSP) and OC use. Risk factors for CT infection were young age (<=20 years) and young age at FSI (<=18 years). HSV-2 infection risk increased with age (>20 years) and >1 LSP. SIGNIFICANCE: Considering the prevalence of HPV and CT in Yc positive samples, we hypothesize a current infection due to recent sexual activity. The study of Yc PCR may add information as (i) a predictor of STI transmission and (ii) an indicative biomarker to validate self-reported condom use. PMID- 26281917 TI - Moderate-intensity exercise training elevates serum and pancreatic zinc levels and pancreatic ZnT8 expression in streptozotocin-induced diabetic rats. AB - AIMS: Diabetes mellitus is associated with disturbed zinc homeostasis and down regulation of zinc transporter 8 (ZnT8); these changes contribute to the defective biosynthesis, storage, and secretion of insulin. Previous studies have reported an improvement in diabetic status and insulin levels in diabetic rats that underwent moderate exercise training, but the mechanisms underlying this effect remain unclear. Evidence shows that exercise training increases the zinc content in the muscle, liver, and kidney of diabetic rats and increases the expression of several types of zinc transporters in the rat hippocampus. We hypothesised that moderate exercise training may increase serum and pancreatic zinc levels, as well as pancreatic ZnT8 expression, in diabetic rats. MAIN METHODS: Wistar rats were divided into 3 equally sized groups: sedentary normal control, sedentary diabetic, and exercise-trained diabetic groups. Diabetes was induced by an intraperitoneal injection of streptozotocin. The 6-week exercise training intervention involved 30 min of moderate-intensity running on a treadmill once daily (5 days/week). At the end of the study, the concentrations of serum and pancreatic zinc were determined using atomic absorptive spectrophotometry. Pancreatic ZnT8 expression was analysed by quantitative real time RT-PCR. KEY FINDINGS: Diabetes caused reductions in the serum and pancreatic zinc levels and pancreatic ZnT8 expression. Following moderate exercise training, there was a significant increase in all of these parameters. SIGNIFICANCE: The ability of moderate exercise training to ameliorate the reductions in serum and pancreatic zinc levels and pancreatic ZnT8 expression can partly explain the beneficial effects of exercise training in diabetes. PMID- 26281918 TI - The potential physiological crosstalk and interrelationship between two sovereign endogenous amines, melatonin and homocysteine. AB - The antioxidant melatonin and the non-proteinogenic excitotoxic amino acid homocysteine (Hcy) are very distinct but related reciprocally to each other in their mode of action. The elevated Hcy level has been implicated in several disease pathologies ranging from cardio- and cerebro-vascular diseases to neurodegeneration owing largely to its free radical generating potency. Interestingly, melatonin administration potentially normalizes the elevated Hcy level, thereby protecting the cells from the undesired Hcy-induced excitotoxicity and cell death. However, the exact mechanism and between them remain obscure. Through literature survey we have found an indistinct but a vital link between melatonin and Hcy i.e., the existence of reciprocal regulation between them, and this aspect has been thoroughly described herein. In this review, we focus on all the possibilities of co-regulation of melatonin and Hcy at the level of their production and metabolism both in basal and in pathological conditions, and appraised the potential of melatonin in ameliorating homocysteinemia-induced cellular stresses. Also, we have summarized the differential mode of action of melatonin and Hcy on health and disease states. PMID- 26281920 TI - Unraveling the Degradation Process of LiNi0.8Co0.15Al0.05O2 Electrodes in Commercial Lithium Ion Batteries by Electronic Structure Investigations. AB - The degradation of LiNi0.8Co0.15Al0.05O2 (LNCAO) is reflected by the electrochemical performance in the fatigued state and correlated with the redox behavior of these cathodes. The detailed electrochemical performance of these samples is investigated by galvanostatic and voltammetric cycling as well as with the galvanostatic intermittent titration technique (GITT). Near-edge X-ray absorption fine structure (NEXAFS) spectroscopy was used to investigate the oxidation state of all three materials at the Ni L2,3, O K, and Co L2,3 edges at five different states of charge. Surface and more bulklike properties are distinguished by total electron yield (TEY) and fluorescence yield (FY) measurements. The electrochemical investigations revealed that the changes in the cell performance of the differently aged materials can be explained by considering the reaction kinetics of the intercalation/deintercalation process. The failure of the redox process of oxygen and nickel at low voltages leads to a significant decrease of the reaction rates in the fatigued cathodes. The accompanied cyclic voltammogram (CV) peaks appear as two peaks because of the local minimum of the reaction rate, although it is one peak in the CV of the calendarically aged LNCAO. The absence of the oxidation/reduction process at low voltages can be traced back to changes in the surface morphology (formation of a NiO-like structure). Further consequences of these material changes are overpotentials, which lead to capacity losses of up to 30% (cycled with a C/3 rate). PMID- 26281919 TI - Intermittent cold exposure improves glucose homeostasis associated with brown and white adipose tissues in mice. AB - AIMS: The discovery of different shades of fat has been implicated in the pathogenesis of obesity-related metabolic disorders. However, the effects of early and intermittent exposure to cold temperature on systemic metabolic changes in adult life remain unclear. MAIN METHODS: To elucidate the impact of cold temperature exposure on metabolic function of adipose tissues, we investigated the glucose homeostasis, activation of brown adipose tissue (BAT) and "browning" of white adipose tissue (WAT) in mice in response to intermittent cold exposure. Mice were exposed to 4 degrees C, 2h per day and 5 days per week, for 14 weeks. Glucose homeostasis was tested via intraperitoneal glucose tolerance test and insulin tolerance test; body fat mass was evaluated using in vivo magnetic resonance imaging; BAT activity was detected primarily by positron emission tomography/computed tomography; and WAT "browning" was evaluated using immunohistochemistry. KEY FINDINGS: Our results showed that a 14-week cold exposure improved glucose tolerance and enhanced insulin sensitivity, reduced the relative weights of epididymal and retroperitoneal WAT, increased expressions of UCP1 and PGC1alpha in subcutaneous adipose tissue. SIGNIFICANCE: Intermittent exposure to cold temperature in early life may improve systemic glucose homeostasis and induce WAT "browning", suggesting that an ambient cold temperature exposure may serve as a promising intervention to metabolic disorders. PMID- 26281921 TI - Charge Transport Limitations in Self-Assembled TiO2 Photoanodes for Dye Sensitized Solar Cells. AB - Solid-state dye-sensitized solar cells offer the possibility of high-power conversion efficiencies due to theoretically lower fundamental losses in dye regeneration. Despite continuous progress, limitations in charge diffusion through the mesoporous photoanode still constrain the device thickness and hence result in reduced light absorption with the most common sensitizers. Here we examine block copolymer-assembled photoanodes with similar surface area and morphology but a large variation in crystal size. We observe that the crystal size has a profound effect on the electron transport, which is not explicable by considering solely the ratio between free and trapped electrons. Our results are consistent with the long-range mobility of conduction band electrons being strongly influenced by grain boundaries. Therefore, maximizing the crystal size while maintaining high enough surface area will be an important route forward. PMID- 26281922 TI - Simple Analytic Description of Collection Efficiency in Organic Photovoltaics. AB - The collection of charge carriers is a fundamental step in the photovoltaic conversion process. In disordered organic films, low mobility and disorder can make collection the performance-limiting step in energy conversion. We derive two analytic relationships for carrier collection efficiency in organic photovoltaics that account for the presence or absence of carrier-selective electrodes. These equations directly include drift and diffusive carrier transport in the device active layers and account for possible losses from Langevin and Shockley-Read Hall recombination mechanisms. General relationships among carrier mobility, contact selectivity, recombination processes, and organic photovoltaic figures of merit are established. Our results suggest that device collection efficiency remains mobility-limited for many materials systems, and a renewed emphasis should be placed on materials' purity. PMID- 26281923 TI - The Active Site Loop Modulates the Reorganization Energy of Blue Copper Proteins by Controlling the Dynamic Interplay with Solvent. AB - Understanding the factors governing the rate of electron transfer processes in proteins is crucial not only to a deeper understanding of redox processes in living organisms but also for the design of efficient devices featuring biological molecules. Here, molecular dynamics simulations performed on native azurin and four chimeric cupredoxins allow for the calculation of the reorganization energy and of structure-related quantities that were used to clarify the molecular determinants to the dynamics/function relationship in blue copper proteins. We find that the dynamics of the small, metal-binding loop region controls the outer-sphere reorganization energy not only by determining the exposure of the active site to solvent but also through the modulation of the redox-dependent rearrangement of the whole protein scaffold and of the surrounding water molecules. PMID- 26281924 TI - Photoisomerization of Pre- and Provitamin D3 in EPA at 77 K: One-Bond-Twist, Not Hula-Twist. AB - The photoisomerizations of previtamin D3 (Pre) and provitamin D3 (Pro) in EPA at 77 K were monitored using fluorescence spectroscopy. In the glassy EPA medium equilibrated tachysterol (Tachy) exists as a mixture of three conformers, the major of which we assign to s-trans,s-cis- and s-cis,s-cis-conformers (tEc- and cEc-Tachy). By contrast, Pre exists exclusively as the s-cis,s-cis-conformer (cZc Pre) and undergoes cis -> trans photoisomerization to cEc-Tachy. Light-induced ring-opening of Pro gives three Pre conformers, the major of which is tZc-Pre instead of the expected cZc-Pre. Curve resolution based on singular value decomposition yields the fluorescence spectra of the conformers. Structural assignments are based on experimental and theoretical evidence showing that the s cis,s-cis-conformers of Pre and Tachy absorb UV light to the red of s-trans-s-cis conformers. The photoisomerizations of tZc- and cZc-Pre in EPA proceed by the one bond twist (OBT) mechanism to give tEc- and cEc-Tachy, respectively. PMID- 26281925 TI - CuInS2-Sensitized Quantum Dot Solar Cell. Electrophoretic Deposition, Excited State Dynamics, and Photovoltaic Performance. AB - Ternary metal chalcogenides such as CuInS2 offer new opportunities to design quantum dot solar cells (QDSC). Chemically synthesized CuInS2 quantum dots (particle diameter, 2.6 nm) have been successfully deposited within the mesoscopic TiO2 film using electrophoretic deposition (150 V cm(-1) dc field). The primary photoinduced process of electron injection from excited CuInS2 into TiO2 occurs with a rate constant of 5.75 * 10(11) s(-1). The TiO2/CuInS2 films are photoactive and produce anodic photocurrent with a power conversion efficiency of 1.14%. Capping the TiO2/CuInS2 film with a CdS layer decreases the interfacial charge recombination and thus offers further improvement in the power conversion efficiency (3.91%). The synergy of using CdS as a passivation layer in the composite film is also evident from the increased external quantum efficiency of the electrode in the red region where only CuInS2 absorbs the incident light. PMID- 26281926 TI - Surface-Accelerated Decomposition of delta-HMX. AB - Despite extensive efforts to study the explosive decomposition of HMX, a cyclic nitramine widely used as a solid fuel, explosive, and propellant, an understanding of the physicochemical processes, governing the sensitivity of condensed HMX to detonation initiation is not yet achieved. Experimental and theoretical explorations of the initiation of chemistry are equally challenging because of many complex parallel processes, including the beta-delta phase transition and the decomposition from both phases. Among four known polymorphs, HMX is produced in the most stable beta-phase, which transforms into the most reactive delta-phase under heat or pressure. In this study, the homolytic NO2 loss and HONO elimination precursor reactions of the gas-phase, ideal crystal, and the (100) surface of delta-HMX are explored by first principles modeling. Our calculations revealed that the high sensitivity of delta-HMX is attributed to interactions of surfaces and molecular dipole moments. While both decomposition reactions coexist, the exothermic HONO-isomer formation catalyzes the N-NO2 homolysis, leading to fast violent explosions. PMID- 26281927 TI - Dynamics of Charge-Transfer Processes with Time-Dependent Density Functional Theory. AB - We show that whenever an electron transfers between closed-shell molecular fragments, the exact correlation potential of time-dependent density functional theory develops a step and peak structure in the bonding region. This structure has a density dependence that is nonlocal both in space and in time that even the exact adiabatic ground-state exchange-correlation functional fails to capture it. For charge-transfer between open-shell fragments, an initial step and peak vanish as the charge-transfer state is reached. The inability of usual approximations to develop these structures leads to inaccurate charge-transfer dynamics. This is illustrated by the complete lack of Rabi oscillations in the dipole moment under conditions of resonant charge transfer for an exactly solvable model system. The results transcend the model and are applicable to more realistic molecular complexes. PMID- 26281928 TI - Polarity-Free Epitaxial Growth of Heterostructured ZnO/ZnS Core/Shell Nanobelts. AB - Surface-polarity-induced formation of ZnO/ZnS heterojunctions has a common characteristic that ZnS (or ZnO) is exclusively decorated on a Zn-terminated (0001) surface of ZnO (or ZnS) due to its comparatively chemically active nature to an O (or S)-terminated (000-1) surface. Here, we report a polarity-free and symmetrical growth of ZnS on both ZnO+/-(0001) surfaces to form a new heterostructured ZnO/ZnS core/shell nanobelt via a thermal evaporation method. Remarkably, the ZnS shell is single-crystalline and preserves the structure and orientation of the inner ZnO nanobelt with an epitaxial relationship of (0001)ZnO//(0001)ZnS; [2-1-10]ZnO//[2-1-10]ZnS. Through this case, we demonstrate that an anion-terminated polar surface could also drive the nucleation and growth of nanostructures as the cation-terminated surface by controlling the growth kinetics. Considering high-performance devices based on ZnO/ZnS heterojunctions, the current ZnO/ZnS nanobelt is advantageous for optoelectronic applications due to its single-crystalline nature and relatively more efficient charge separation along 3D heterointerfaces. PMID- 26281929 TI - Functional Role of Pyridinium during Aqueous Electrochemical Reduction of CO2 on Pt(111). AB - Recent breakthroughs in electrochemical studies have reported aqueous CO2 reduction to formic acid, formaldehyde, and methanol at low overpotentials (-0.58 V versus SCE), with a Pt working electrode in acidic pyridine (Pyr) solutions. We find that CO2 is reduced by H atoms bound to the Pt surface that are transferred as hydrides to CO2 in a proton-coupled hydride transfer (PCHT) mechanism activated by pyridinium (PyrH(+)), CO2 + Pt-H + PyrH(+) + e(-) -> Pyr + Pt + HCO2H. The surface-bound H atoms consumed by CO2 reduction is replenished by the one-electron reduction of PyrH(+) through the proton-coupled electron transfer (PCET), PyrH(+) + Pt + e(-) -> Pyr + Pt-H. Pyridinium is essential to establish a high concentration of Bronsted acid in contact with CO2 and with the Pt surface, much higher than the concentration of free protons. These findings are particularly relevant to generate fuels with a carbon-neutral footprint. PMID- 26281930 TI - Graphene-Based Photocatalysts for Hydrogen Generation. AB - Graphene-based photocatalysts have gained increasing interest as a viable alternate to increase photocatalytic H2 production performance in converting solar energy into chemical energy. The use of graphene to enhance the efficiency of photocatalysts has been proved due to its unique two-dimensional conjugated structure and electronic properties. In this Perspective, we have summarized the recent significant advances on the design and applications of graphene-based photocatalytic composites. The rational designs for high-performance photocatalysts using graphene-based materials are described. The applications of the new materials in photocatalytic hydrogen evolution are presented. Finally, the ongoing challenges and opportunities for the future development of graphene based photocatalysts are also proposed. PMID- 26281931 TI - Luminophores and Carbon Nanotubes: An Odd Combination? AB - Studies on the exohedral and endohedral functionalization of carbon nanotubes (CNTs) with organic or inorganic chromophores and luminophores have increased substantially in recent years, making use of covalent, supramolecular, electrostatic, and host-guest preparative strategies. Research in this field has fundamental interest because the mixing of two radically different components (molecule/metal complex versus CNT) typically affords materials with exceptional electronic and structural properties while also offering the possibility of studying in detail the interactions between molecules/complexes and nanomaterials. Application perspectives can be also envisaged, particularly in the areas of light-to-electricity (e.g., photovoltaics) and electricity-to-light (e.g., electroluminescence) conversion. Here, we focus in particular on some recent results obtained in the preparation of luminescent hybrids in which suitably designed emitting moieties, placed inside or outside of carbon nanotubes through noncovalent interactions, can afford brightly glowing black photoluminescent nanostructures. PMID- 26281933 TI - Calcium and the Hydrogen-Bonded Water Network in the Photosynthetic Oxygen Evolving Complex. AB - In photosynthesis, photosystem II evolves oxygen from water at a Mn4CaO5 cluster (OEC). Calcium is required for biological oxygen evolution. In the OEC, a water network, extending from the calcium to four peptide carbonyl groups, has recently been predicted by a high-resolution crystal structure. Here, we use carbonyl vibrational frequencies as reporters of electrostatic changes to test the presence of this water network. A single flash, oxidizing Mn(III) to Mn(IV) (the S1 to S2 transition), upshifted the frequencies of peptide C?O bands. The spectral change was attributable to a decrease in C?O hydrogen bonding. Strontium, which supports a lower level of steady state activity, also led to an oxidation-induced shift in C?O frequencies, but treatment with barium and magnesium, which do not support activity, did not. This work provides evidence that calcium maintains an electrostatically responsive water network in the OEC and shows that OEC peptide carbonyl groups can be used as solvatochromic markers. PMID- 26281932 TI - Negative Ion Photoelectron Spectroscopy Reveals Thermodynamic Advantage of Organic Acids in Facilitating Formation of Bisulfate Ion Clusters: Atmospheric Implications. AB - Recent lab and field measurements have indicated critical roles of organic acids in enhancing new atmospheric aerosol formation. Such findings have stimulated theoretical studies with the aim of understanding the interaction of organic acids with common aerosol nucleation precursors like bisulfate (HSO4(-)). We report a combined negative ion photoelectron spectroscopic and theoretical investigation of molecular clusters formed by HSO4(-) with succinic acid (SUA, HO2C(CH2)2CO2H), HSO4(-)(SUA)n (n = 0-2), along with HSO4(-)(H2O)n and HSO4( )(H2SO4)n. It is found that one SUA molecule can stabilize HSO4(-) by ca. 39 kcal/mol, three times the corresponding value that one water molecule is capable of (ca. 13 kcal/mol). Molecular dynamics simulations and quantum chemical calculations reveal the most plausible structures of these clusters and attribute the stability of these clusters to the formation of strong hydrogen bonds. This work provides direct experimental evidence showing significant thermodynamic advantage by involving organic acid molecules to promote formation and growth in bisulfate clusters and aerosols. PMID- 26281934 TI - Ultrafast Exciton Self-Trapping upon Geometry Deformation in Perylene-Based Molecular Aggregates. AB - Femtosecond time-resolved experiments demonstrate that the photoexcited state of perylene tetracarboxylic acid bisimide (PBI) aggregates in solution decays nonradiatively on a time-scale of 215 fs. High-level electronic structure calculations on dimers point toward the importance of an excited state intermolecular geometry distortion along a reaction coordinate that induces energy shifts and couplings between various electronic states. Time-dependent wave packet calculations incorporating a simple dissipation mechanism indicate that the fast energy quenching results from a doorway state with a charge transfer character that is only transiently populated. The identified relaxation mechanism corresponds to a possible exciton trap in molecular materials. PMID- 26281935 TI - Prediction of the Critical Micelle Concentration of Nonionic Surfactants by Dissipative Particle Dynamics Simulations. AB - Micellization of surfactant solutions is a ubiquitous phenomenon in natural systems and technological processes, and its theoretical description represents one of the cornerstone problems in the physical chemistry of colloidal systems. However, successful attempts of quantitative modeling confirmed by experimental data remains limited. We show, for the first time, that the dissipative particle dynamics with rigorously defined soft repulsion interaction and rigidity parameters is capable of predicting micellar self-assembly of nonionic surfactants. This is achieved due to a novel approach suggested for defining the interaction parameters by fitting to the infinite dilution activity coefficients of binary solutions formed by reference compounds that represent coarse-grained fragments of surfactant molecules. Using this new parametrization scheme, we obtained quantitative agreement with the experimental critical micelle concentration and aggregation number for several typical surfactants of different chemical structures. The proposed approach can be extended to various colloidal and polymeric systems beyond nonionic surfactant solutions. PMID- 26281936 TI - Limits on the Fill Factor in Organic Photovoltaics: Distinguishing Nongeminate and Geminate Recombination Mechanisms. AB - In this Letter, we present transient optoelectronic experimental studies of the recombination processes limiting the fill factor (FF) in three conjugated polymer:fullerene systems, poly(3-hexylthiophene) (P3HT) and two lower-band-gap polymers that exhibit lower FFs poly[2,6-(4,4-bis-(2-ethylhexyl)-4H cyclopenta[2,1-b;3,4-b']dithiophene)-alt-4,7-(2,1,3-benzothiadiazole) (PCPDTBT) and poly(2,7-(9,9-dioctylfluorene)-alt-5,5-(4',7'-di-2-thienyl-2',1',3' benzothiadiazole)) (APFO-3). Using transient absorption spectroscopy, charge extraction, and transient photovoltage experiments, we show that the lower FF observed for the PCPDTBT-based device results from enhanced nongeminate recombination even at short circuit, In contrast, we show that for APFO-3 devices, the FF is primarily limited by a voltage-dependent free charge generation, which we assign to a geminate recombination process. PMID- 26281937 TI - Charge Transport in Pentacene-Graphene Nanojunctions. AB - We investigate charge transport in pentacene-graphene nanojunctions employing density functional theory (DFT) electronic structure calculations and the Landauer transport formalism. The results show that the unique electronic properties of graphene strongly influence the transport in the nanojunctions. In particular, edge states in graphene electrodes with zigzag termination result in additional transport channels close to the Fermi energy, which deeply affects the conductance at small bias voltages. Investigating different linker groups as well as chemical substitution, we demonstrate how the transport properties are furthermore influenced by the molecule-lead coupling and the energy level lineup. PMID- 26281938 TI - Water-Peptide Dynamics during Conformational Transitions. AB - Transitions between metastable conformations of a dipeptide are investigated using classical molecular dynamics simulation with explicit water molecules. The distribution of the surrounding water at different moments before the transitions and the dynamical correlations of water with the peptide's configurational motions indicate that the water molecules represent an integral part of the molecular system during the conformational changes, in contrast with the metastable periods when water and peptide dynamics are essentially decoupled. PMID- 26281939 TI - Propagative Sidewall Alkylcarboxylation that Induces Red-Shifted Near-IR Photoluminescence in Single-Walled Carbon Nanotubes. AB - Semiconducting single-walled carbon nanotubes (SWCNTs) are direct band gap materials in which exciton photoluminescence (PL) occurs at the same wavelength as excitation. Here, we show that propagative sidewall alkylation can induce a new PL peak in (6,5) SWCNTs red-shifted from the E11 near-infrared exciton excitation and emission by ~140 meV. The magnitude of the red-shift is weakly dependent on the terminal functional group. This new emission peak is relatively bright even after a high degree of functionalization because the reaction occurs by propagating outward from initial defects, creating bands of functional groups while maintaining the number of effective defect sites. Density functional theory computations suggest that the covalently attached alkyl functional groups introduce a new, optically allowed, low-lying state from which this new emission may arise. This method of shifting nanotube PL away from the bare nanotube excitation may find applications in near-infrared (IR) fluorescence imaging by allowing both excitation and emission to occur in the optically transparent window for biological tissues. PMID- 26281940 TI - Graphene Films for Flexible Organic and Energy Storage Devices. AB - Graphene and its derivatives have been the subject of extensive research in fundamental science and have viable applications in current and future technology. The exceptionally high electronic and thermal conductivity, optical transparency, and high specific surface area, combined with excellent mechanical flexibility and environmental stability leave graphene poised to be a material of the future. This perspective introduces the importance of graphene electrodes, discusses the synthesis of graphene and transfer onto desired substrates and the role of graphene in electrodes for a broad range of flexible devices such as photovoltaic, electronic, and electrochemical energy storage. PMID- 26281941 TI - Nanocarbon Hybrids: Interactions with Luminophores to Applications in Energy Harvesting and Solar Fuel Production. PMID- 26281942 TI - [The frontage and the other headlines]. PMID- 26281943 TI - Impact of Weight Changes After the Diagnosis of Stage III Colon Cancer on Survival Outcomes. AB - BACKGROUND: Weight modification after a diagnosis of colon cancer and its impact on outcomes remain unclear. Thus we aimed to examine the association of obesity and weight changes from baseline oncology consultation with recurrence-free survival (RFS) and overall survival (OS) in patients with stage III colon cancer. METHODS: Patients aged >= 18 years who were diagnosed with stage III colon cancer in British Columbia from 2008 to 2010 and who received adjuvant chemotherapy were included in the study. Cox proportional hazards regression models were fitted to evaluate the impact of different body compositions and degree of weight changes from baseline assessment with outcomes while controlling for potentially confounding covariates, such as age and sex. RESULTS: A total of 539 patients with stage III colon cancer were included: median age was 69 years (range, 26-94 years), 52% were men, and 53% had Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Those with weight gains of >= 10% had a median RFS of 37 months compared with 49 months in those with weight gains of < 10% (hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.56-1.59; P = .82). However, this finding was not significant. In Cox models, patients who exhibited weight losses of >= 10% experienced significantly inferior RFS (HR, 3.45; 95% CI, 1.44 8.13; P = .0046) and OS (HR, 2.63; 95% CI, 1.04-6.67; P = .041) compared with those who experienced weight losses of < 10%. Weight gains, losses, or changes of equal or less magnitude did not show any significant associations with outcomes (all P > .05). CONCLUSIONS: Weight losses of >= 10% from baseline evaluation bodes a worse prognosis among patients with stage III colon cancer. PMID- 26281944 TI - Alpha-1 antitrypsin deficiency caused by a novel mutation (p.Leu263Pro): Pi*ZQ0gaia - Q0gaia allele. AB - Severe alpha-1 antitrypsin deficiency (AATD) is generally associated with PI*ZZ genotype and less often with combinations of PI*Z, PI*S, and other rarer deficiency or null (Q0) alleles. Severe AATD predisposes patients to various diseases, including pulmonary emphysema. Presented here is a case report of a young man with COPD and AATD. The investigation of the AATD showed a novel mutation p.Leu263Pro (c.860T>C), which was named Q0gaia (Pi*ZQ0gaia). Q0gaia is associated with very low or no detectable serum concentrations of AAT. PMID- 26281946 TI - Manual Physical Therapy Versus Surgery for Carpal Tunnel Syndrome: A Randomized Parallel-Group Trial. AB - This randomized clinical trial investigated the effectiveness of surgery compared with physical therapy consisting of manual therapies including desensitization maneuvers in carpal tunnel syndrome (CTS). The setting was a public hospital and 2 physical therapy practices in Madrid, Spain. One hundred twenty women with CTS were enrolled between February 2013 and January 2014, with 1-year follow-up completed in January 2015. Interventions consisted of 3 sessions of manual therapies including desensitization maneuvers of the central nervous system (physical therapy group, n = 60) or decompression/release of the carpal tunnel (surgical group, n = 60). The primary outcome was pain intensity (mean pain and the worst pain), and secondary outcomes included functional status and symptoms severity subscales of the Boston Carpal Tunnel Questionnaire and the self perceived improvement. They were assessed at baseline and 1, 3, 6, and 12 months by a blinded assessor. Analysis was by intention to treat. At 12 months, 111 (92%) women completed the follow-up (55/60 physical therapy, 56/60 surgery). Adjusted analyses showed an advantage (all, P < .01) for physical therapy at 1 and 3 months in mean pain (Delta -2.0 [95% confidence interval (CI) -2.8 to 1.2]/-1.3 [95% CI -2.1 to -.6]), the worst pain (Delta -2.9 [-4.0 to -2.0]/-2.0 [ 3.0 to -.9]), and function (Delta -.8 [-1.0 to -.6]/-.3 [-.5 to -.1]), respectively. Changes in pain and function were similar between the groups at 6 and 12 months. The 2 groups had similar improvements in the symptoms severity subscale of the Boston Carpal Tunnel Questionnaire at all follow-ups. In women with CTS, physical therapy may result in similar outcomes on pain and function to surgery. TRIAL REGISTRATION: http://www.clinicaltrials.gov, ClinicalTrials.gov, NCT01789645. PERSPECTIVE: This study found that surgery and physical manual therapies including desensitization maneuvers of the central nervous system were similarly effective at medium-term and long-term follow-ups for improving pain and function but that physical therapy led to better outcomes in the short term. PMID- 26281947 TI - Effects of a Guided Internet-Delivered Self-Help Intervention for Adolescents With Chronic Pain. AB - Cognitive-behavioral therapy (CBT) is effective in reducing the frequency and intensity of chronic pain in adolescents. However, CBT seems not to be considered acceptable by all adolescents. The main aim of our study was therefore to evaluate the effects of guided Internet-delivered self-help for adolescents with chronic pain. Adolescents (N = 69) were assessed on the outcome measures of pain, coping, disability, catastrophizing, rewarding of pain behavior by parents, and quality of life. Measures were taken 7 weeks before treatment and at pretreatment, posttreatment, and 3-month follow-up. Multilevel modeling was used for longitudinal analysis of the data. Pain intensity, interference caused by pain, rewarding of pain behavior by parents, and sleep problems significantly decreased during the intervention. The quality-of-life scores for pain, general behavior, mental health, family activities, and health changes also significantly improved during the intervention. With regard to coping, only problem-focused avoidance behavior significantly increased. No significant differences were found for pain-related disability and pain catastrophizing. Contrary to expectations, guided Internet-delivered self-help for chronic pain is difficult to use in adolescents, resulting in treatment attrition and loss to follow-up. TRIAL REGISTRATION: Dutch Trial Register NTR1926. PERSPECTIVE: The results of this trial suggest that Internet-based self-management is effective in decreasing pain intensity in adolescents with chronic pain. Because the intervention is grounded in CBT, we expect the underlying mechanism to be a change in self-management skills and in the ability of challenging dysfunctional thoughts. PMID- 26281948 TI - Evidence for Sustained Mechanical Pain Sensitization in Women With Chronic Temporomandibular Disorder Versus Healthy Female Participants. AB - Generalized dysfunction of the nociceptive system has been hypothesized to be an important pathophysiologic process underlying temporomandibular disorder (TMD) pain. Studies have not identified sensitization to painful stimuli administered prospectively across consecutive days among participants with TMD with chronic pain. We attempted to isolate an empirically derived laboratory-based marker of sustained mechanical pain sensitization. We examined whether this index accounted for variance in prospective assessments of clinical TMD pain. Participants were women with a clinical diagnosis of chronic TMD (n = 30) and healthy female controls (n = 30). Pain thresholds were assessed using digital algometry 4 times at 12-hour intervals over 48 consecutive hours and clinical TMD pain via follow up telephone assessments. Sustained mechanical pain sensitization, defined by statistically significant linear decrements in pressure pain thresholds across the consecutive testing sessions, discriminated chronic TMD and control participants. An index of sustained sensitization at the masseter accounted for unique variance in clinical TMD pain over the subsequent 3-month assessment period, even controlling for mean pain threshold and baseline pain severity. These preliminary findings highlight discriminant and predictive validity characteristics of a novel marker of protracted pain sensitization among women with chronic TMD pain. PERSPECTIVE: A laboratory-based and empirically defined marker of sustained mechanical pain sensitization over the course of days with acceptable discriminant and predictive validity was identified. This marker may represent a clinically useful marker of chronic TMD pain in women. PMID- 26281949 TI - Polyphenols: From Plants to a Variety of Food and Nonfood Uses. AB - Polyphenols are major plant secondary metabolites, structurally extremely diverse, essential for a variety of functions in plants, responsible for major organoleptic and nutritional properties of plant-derived foods, and useful for numerous practical applications. During the 27th International Conference on Polyphenols and 8th Tannin Conference, held jointly in September 2014 in Nagoya, Japan (ICP2014), the latest advances in polyphenol research have been presented. These include advances in polyphenol chemistry, physicochemistry, and materials science; their biosynthesis, genetics, and metabolic engineering; and their role in plant interactions with the environment, in nutrition and health, and in natural medicine. This special issue presents a selection of research papers presented at the meeting, covering these different fields. Major recent progress and perspectives in these areas are also outlined in this introductory paper. PMID- 26281950 TI - [Anti-NMDA antibody encephalitis secondary to herpes simplex virus infection]. PMID- 26281945 TI - Nrf2--a therapeutic target for the treatment of neurodegenerative diseases. AB - The brain is very sensitive to changes in redox status; thus maintaining redox homeostasis in the brain is critical for the prevention of accumulating oxidative damage. Aging is the primary risk factor for developing neurodegenerative diseases. In addition to age, genetic and environmental risk factors have also been associated with disease development. The primary reactive insults associated with the aging process are a result of oxidative stress (OS) and nitrosative stress (NS). Markers of increased oxidative stress, protein and DNA modification, inflammation, and dysfunctional proteostasis have all been implicated in contributing to the progression of neurodegeneration. The ability of the cell to combat OS/NS and maintain a clearance mechanism for misfolded aggregating proteins determines whether or not it will survive. A critical pathway in this regard is the Nrf2 (nuclear factor erythroid 2-related factor 2)- antioxidant response element (ARE) pathway. Nrf2 activation has been shown to mitigate a number of pathologic mechanisms associated with Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. This review will focus on the role of Nrf2 in these diseases and the potential for Nrf2 activation to attenuate disease progression. PMID- 26281951 TI - [Open de doors on the ICU. An unavoidable necessity]. PMID- 26281953 TI - What Is Evidence-Based About Myofascial Chains: A Systematic Review. AB - OBJECTIVE: To provide evidence for the existence of 6 myofascial meridians proposed by Myers based on anatomic dissection studies. DATA SOURCES: Relevant articles published between 1900 and December 2014 were searched in MEDLINE (PubMed), ScienceDirect, and Google Scholar. STUDY SELECTION: Peer-reviewed human anatomic dissection studies reporting morphologic continuity between the muscular constituents of the examined meridians were included. If no study demonstrating a structural connection between 2 muscles was found, articles on general anatomy of the corresponding body region were targeted. DATA EXTRACTION: Continuity between 2 muscles was documented if 2 independent investigators agreed that it was reported clearly. Also, 2 independent investigators rated methodologic quality of included studies by means of a validated assessment tool (Quality Appraisal for Cadaveric Studies). DATA SYNTHESIS: The literature search identified 6589 articles. Of these, 62 article met the inclusion criteria. The studies reviewed suggest strong evidence for the existence of 3 myofascial meridians: the superficial back line (all 3 transitions verified, based on 14 studies), the back functional line (all 3 transitions verified, based on 8 studies) and the front functional line (both transitions verified, based on 6 studies). Moderate-to strong evidence is available for parts of the spiral line (5 of 9 verified transitions, based on 21 studies) and the lateral line (2 of 5 verified transitions, based on 10 studies). No evidence exists for the superficial front line (no verified transition, based on 7 studies). CONCLUSIONS: The present systematic review suggests that most skeletal muscles of the human body are directly linked by connective tissue. Examining the functional relevance of these myofascial chains is the most urgent task of future research. Strain transmission along meridians would both open a new frontier for the understanding of referred pain and provide a rationale for the development of more holistic treatment approaches. PMID- 26281952 TI - Conjugates of gamma-Carbolines and Phenothiazine as new selective inhibitors of butyrylcholinesterase and blockers of NMDA receptors for Alzheimer Disease. AB - Alzheimer disease is a multifactorial pathology and the development of new multitarget neuroprotective drugs is promising and attractive. We synthesized a group of original compounds, which combine in one molecule gamma-carboline fragment of dimebon and phenothiazine core of methylene blue (MB) linked by 1-oxo and 2-hydroxypropylene spacers. Inhibitory activity of the conjugates toward acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and structurally close to them carboxylesterase (CaE), as well their binding to NMDA-receptors were evaluated in vitro and in silico. These newly synthesized compounds showed significantly higher inhibitory activity toward BChE with IC50 values in submicromolar and micromolar range and exhibited selective inhibitory action against BChE over AChE and CaE. Kinetic studies for the 9 most active compounds indicated that majority of them were mixed-type BChE inhibitors. The main specific protein-ligand interaction is pi-pi stacking of phenothiazine ring with indole group of Trp82. These compounds emerge as promising safe multitarget ligands for the further development of a therapeutic approach against aging related neurodegenerative disorders such as Alzheimer and/or other pathological conditions. PMID- 26281954 TI - Physiotherapy Rehabilitation for People With Progressive Multiple Sclerosis: A Systematic Review. AB - OBJECTIVE: To assess the efficacy of physiotherapy interventions, including exercise therapy, for the rehabilitation of people with progressive multiple sclerosis. DATA SOURCES: Five databases (Cochrane Library, Physiotherapy Evidence Database [PEDro], Web of Science Core Collections, MEDLINE, Embase) and reference lists of relevant articles were searched. STUDY SELECTION: Randomized experimental trials, including participants with progressive multiple sclerosis and investigating a physiotherapy intervention or an intervention containing a physiotherapy element, were included. DATA EXTRACTION: Data were independently extracted using a standardized form, and methodologic quality was assessed using the PEDro scale. DATA SYNTHESIS: Thirteen studies (described by 15 articles) were identified and scored between 5 and 9 out of 10 on the PEDro scale. Eight interventions were assessed: exercise therapy, multidisciplinary rehabilitation, functional electrical stimulation, botulinum toxin type A injections and manual stretches, inspiratory muscle training, therapeutic standing, acupuncture, and body weight-supported treadmill training. All studies, apart from 1, produced positive results in at least 1 outcome measure; however, only 1 article used a power calculation to determine the sample size and because of dropouts the results were subsequently underpowered. CONCLUSIONS: This review suggests that physiotherapy may be effective for the rehabilitation of people with progressive multiple sclerosis. However, further appropriately powered studies are required. PMID- 26281955 TI - Moderators, Mediators, and Nonspecific Predictors of Treatment Outcome in an Intervention for Everyday Task Improvement in Persons With Executive Deficits After Brain Injury. AB - OBJECTIVE: To identify moderators, mediators, and predictors of everyday task performance after an experimental combination of errorless learning and goal management training. DESIGN: Predictor analysis of a randomized controlled intervention trial. SETTING: Outpatient rehabilitation centers. PARTICIPANTS: Patients (N=60) with acquired brain injury of nonprogressive nature with a minimal postonset time of 3 months. INTERVENTIONS: Participants were randomly allocated to 8 sessions of errorless or conventional goal management training. MAIN OUTCOME MEASURE: Everyday task performance, assessed at baseline and after treatment by evaluating correct, ineffective, and missing task steps. RESULTS: Demographic variables, neuropsychological test performance, subjective cognitive function, and quality of life were selected as candidate predictors. The results showed that age (P=.03) and estimated intelligence quotient (IQ) (P=.02) emerged as moderators. Higher age was associated with better everyday task performance after conventional goal management training, whereas higher IQ was associated with better performance after errorless goal management training. Higher executive function scores after training predicted improved everyday task performance across the 2 treatment conditions (P=.04). CONCLUSIONS: The identified predictors may contribute to a more tailored cognitive rehabilitation approach in which treatments and patients are better matched when clinicians decide to train everyday tasks. PMID- 26281956 TI - Imaging Cells in Flow Cytometer Using Spatial-Temporal Transformation. AB - Flow cytometers measure fluorescence and light scattering and analyze multiple physical characteristics of a large population of single cells as cells flow in a fluid stream through an excitation light beam. Although flow cytometers have massive statistical power due to their single cell resolution and high throughput, they produce no information about cell morphology or spatial resolution offered by microscopy, which is a much wanted feature missing in almost all flow cytometers. In this paper, we invent a method of spatial-temporal transformation to provide flow cytometers with cell imaging capabilities. The method uses mathematical algorithms and a spatial filter as the only hardware needed to give flow cytometers imaging capabilities. Instead of CCDs or any megapixel cameras found in any imaging systems, we obtain high quality image of fast moving cells in a flow cytometer using PMT detectors, thus obtaining high throughput in manners fully compatible with existing cytometers. To prove the concept, we demonstrate cell imaging for cells travelling at a velocity of 0.2 m/s in a microfluidic channel, corresponding to a throughput of approximately 1,000 cells per second. PMID- 26281957 TI - Putting flu on the agenda: New voices, new partners. PMID- 26281958 TI - Exercise motives and positive body image in physically active college women and men: Exploring an expanded acceptance model of intuitive eating. AB - The acceptance model of intuitive eating posits that body acceptance by others facilitates body appreciation and internal body orientation, which contribute to intuitive eating. Two domains of exercise motives (functional and appearance) may also be linked to these variables, and thus were integrated into the model. The model fit the data well for 406 physically active U.S. college students, although some pathways were stronger for women. Body acceptance by others directly contributed to higher functional exercise motives and indirectly contributed to lower appearance exercise motives through higher internal body orientation. Functional exercise motives positively, and appearance exercise motives inversely, contributed to body appreciation. Whereas body appreciation positively, and appearance exercise motives inversely, contributed to intuitive eating for women, only the latter association was evident for men. To benefit positive body image and intuitive eating, efforts should encourage body acceptance by others and emphasize functional and de-emphasize appearance exercise motives. PMID- 26281959 TI - Degradation of flumequine in aqueous solution by persulfate activated with common methods and polyhydroquinone-coated magnetite/multi-walled carbon nanotubes catalysts. AB - In recent years, flumequine (FLU) has been ubiquitously detected in surface waters and municipal wastewaters. In light of its potential negative impacts to aquatic species, growing concern has been arisen for the removal of this antibiotic from natural waters. In this study, the kinetics, degradation mechanisms and pathways of aqueous FLU by persulfate (PS) oxidation were systematically determined. Three common activation methods, including heat, Fe(2+) and Cu(2+), and a novel heterogeneous catalyst, namely, polyhydroquinone coated magnetite/multi-walled carbon nanotubes (Fe3O4/MWCNTs/PHQ), were investigated to activate PS for FLU removal. It was found that these three common activators enhanced FLU degradation obviously, while several influencing factors, such as solution pH, inorganic ions (especially HCO3(-) at 5 mmol/L) and dissolved organic matter extracts, exerted their different effects on FLU removal. The catalysts were characterized, and an efficient catalytic degradation performance, high stability and excellent reusability were observed. The measured total organic carbon levels suggested that FLU can be effectively mineralized by using the catalysts. Radical mechanism was studied by combination of the quenching tests and electron paramagnetic resonance analysis. It was assumed that sulfate radicals predominated in the activation of PS with Fe3O4/MWCNTs/PHQ for FLU removal, while hydroxyl radicals also contributed to the catalytic oxidation process. In addition, a total of fifteen reaction intermediates of FLU were identified, from which two possible pathways were proposed involving hydroxylation, decarbonylation and ring opening. Overall, this study represented a systematical evaluation regarding the transformation process of FLU by PS, and showed that the heterogeneous catalysts can efficiently activate PS for FLU removal from the water environment. PMID- 26281960 TI - Identification of phototransformation products of the antiepileptic drug gabapentin: Biodegradability and initial assessment of toxicity. AB - The anticonvulsant drug Gabapentin (GAB) is used for the treatment of various diseases (e.g. epilepsy, bipolar disorder, neuropathic pain) and is being consumed in high amounts. As GAB is not metabolized and shows a weak elimination in sewage treatment plants (STPs), it has been detected in surface water and even in raw potable water. Moreover, the confirmed teratogenic effects of GAB indicate the need for further investigations regarding options for the elimination of GAB in the water cycle. Little is known about the behavior of GAB during treatment with UV light, which is normally used for the disinfection of potable water and discussed for advanced wastewater treatment. In this study, GAB was exposed to polychromatic UV irradiation at different initial concentrations in aqueous solution. Afterwards the structures of the resulting phototransformation products (PTPs) were identified and elucidated by means of high-resolution mass spectrometry. GAB and photolytic mixtures were submitted to the Closed Bottle Test (CBT; OECD 301 D) to assess biodegradability. Furthermore, the toxicity of GAB and its photolytic mixtures was initially addressed on screening level using a modified luminescent bacteria test (LBT) and the umu-test (ISO/FDIS 13829). Environmentally realistic concentrations of GAB were disclosed by predicting STP influent concentrations (24.3 and 23.2 MUg L(-1)). GAB with initial concentration of 100 mg L(-1) was eliminated by 80% after 128 min of direct UV irradiation, but just 9% of non-purgeable organic carbon (NPOC) was removed indicating the formation of dead-end transformation products (TPs). Structures of different PTPs were elucidated and several identical PTPs could also be identified at lower initial treatment concentrations (20 mg L(-1), 5 mg L(-1), 1 mg L(-1) and 0.1 mg L(-1)). GAB was classified as not readily biodegradable. Moreover, photo treatment did not result in better biodegradable PTPs. With increasing UV treatment duration, photolytic mixtures of GAB showed an increased inhibition of both, the bacterial luminescence emission as well as the growth in the modified LBT. In the umu-test no significant induction of the umuC gene as an indicator of genotoxicity was observed. Our results show that UV irradiation of GAB containing water would lead to the formation of recalcitrant PTPs. Considering that GAB was found in raw drinking water, the formation of toxic PTPs during drinking water treatment with UV light might be possible. Therefore, further studies should be conducted regarding the fate and effects on human health and the environment of GAB and the PTPs identified within this study. PMID- 26281961 TI - Cerebral aneurysms: Cerebral aneurysm guidelines-more guidance needed. PMID- 26281962 TI - Motor neuron disease: Are diabetes and amyotrophic lateral sclerosis related? PMID- 26281963 TI - Traumatic brain injury: Long-term tau elevation linked to chronic symptoms after brain injury. PMID- 26281964 TI - Motor neuron disease: Diaphragm pacing is associated with reduced survival in ALS patients with respiratory insufficiency. PMID- 26281965 TI - In vitro activity of essential oils extracted from condiments against fluconazole resistant and -sensitive Candida glabrata. AB - In the present study, the antifungal activity of essential oils obtained from Origanum vulgare (oregano), Cinnamomum zeylanicum (cinnamon), Lippia graveolens (Mexican oregano), Thymus vulgaris (thyme), Salvia officinalis (sage), Rosmarinus officinalis (rosemary), Ocimum basilicum (basil) and Zingiber officinale (ginger) were assessed against Candida glabrata isolates. One group contained 30 fluconazole-susceptible C. glabrata isolates, and the second group contained fluconazole-resistant isolates derived from the first group after the in vitro induction of fluconazole-resistance, for a total of 60 tested isolates. The broth microdilution methodology was used. Concentrations of 50MUg/mL, 100MUg/mL, 200MUg/mL, 400MUg/mL, 800MUg/mL, 1600MUg/mL and 3200MUg/mL of the essential oils were used, and the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were determined. Thyme, sage, rosemary, basil and ginger essential oils showed no antifungal activity at the tested concentrations. Antimicrobial activity less than or equal to 3200MUg/mL was observed for oregano, Mexican oregano and cinnamon essential oils. Both the oregano and Mexican oregano essential oils showed high levels of antifungal activity against the fluconazole susceptible C. glabrata group, whereas the cinnamon essential oil showed the best antifungal activity against the fluconazole-resistant C. glabrata isolates. PMID- 26281966 TI - New study on the correlation between carbon dioxide concentration in the environment and radon monitor devices. AB - The influence of high geogenic carbon dioxide concentrations on monitoring devices might present a significant challenge to the measurement of radon concentrations in environments with a high level of carbon dioxide concentration such as volcano sites, mofettes, caves, etc. In this study, the influence of carbon dioxide concentration on several different types of radon monitor devices including Alpha Spectrometry (Sarad RTM 2200, EQF 3220, RAD7), Ionizing Chamber (AlphaGUARD PQ2000 PRO) and Active Cell (Active scintillation cell, Pylon 300A) - was examined to represent new aspects of radon measuring in environments with carbon dioxide. In light of the results, all measuring devices were exposed to variable conditions affected by carbon dioxide concentration, except for the AlphaGUARD, which was kept in a steady state throughout the experiment. It was observed that alpha spectroscopy devices were affected by carbon dioxide, since measured radon concentrations decreased in the presence of 70% and 90% carbon dioxide concentrations by 26.5 +/- 2% and 14.5 +/- 2.5% for EQF 3220, and 32 +/- 2% and 35.5 +/- 2% for RTM 2200. However, the ionizing chamber instrument was unaffected by changes in carbon dioxide concentration. It was determined that the RAD7 performed relatively inefficiently in the presence of carbon dioxide concentrations higher than 67% by an overall efficiency factor of approximately 0.52, confirming that it is not an admissible radon monitor instrument in environments with high carbon dioxide concentrations. PMID- 26281967 TI - Dysfunctional resting-state connectivities of brain regions with structural deficits in drug-naive first-episode schizophrenia adolescents. AB - OBJECTIVE: Individuals with adolescent-onset schizophrenia (AOS) are a subgroup of patients who present clinical symptoms between 13 and 18years of age. Little is known about neurodevelopmental abnormalities in this patient population. The present study was to examine possible resting-state dysfunctional connectivity of brain regions with altered gray matter volume in AOS. METHODS: Gray matter volume was investigated by voxel-based morphometry (VBM) analysis. Resting-state functional connectivity analysis was used to examine the correlations between regions with structural deficits and the remaining regions. RESULTS: Thirty-seven first-episode schizophrenia adolescents and 30 healthy controls were enrolled. Compared to the controls, the patients showed significantly decreased gray matter volumes in the right superior temporal gyrus (STG) and middle temporal gyrus (MTG) (ps<0.05). With the right STG as seed, significantly reduced connectivities were found within the frontal-temporal networks in the patient group (ps<0.05). With the right MTG as seed, the patient group showed significantly reduced connectivities in the default-mode networks and visual networks (ps<0.05). Compared to significant correlations in the controls (p=0.02), the patients had no observed correlations between functional connectivity of the right STG and gray matter volume of this region. Significant positive correlations were found between functional connectivity of the right STG with the left middle frontal gyrus and the Positive and Negative Syndrome Scale total scores (p=0.048) after controlling the confounding variables. CONCLUSIONS: These findings show dysfunctional resting-state connectivities of the right STG and MTG with decreased gray matter volume in adolescents with AOS, suggesting that neurodevelopmental abnormalities may be present in AOS. PMID- 26281968 TI - Flawed analyses undermine proposed relationship between childhood cat ownership and schizophrenia. PMID- 26281969 TI - The hidden history: Her son was killed in Vietnam. PMID- 26281970 TI - Undiagnosed cognitive impairment, health status and depressive symptoms in patients with type 2 diabetes. AB - AIMS: Type 2 diabetes (T2DM) is associated with cognitive impairment. We examined whether undiagnosed cognitive impairment in T2DM-patients is associated with a reduced health status and depressive symptoms. METHODS: In an observational study, 225 T2DM-patients aged >=70years were examined at their homes and (some of them) at a memory clinic for undiagnosed cognitive impairment (dementia or mild cognitive impairment [MCI], defined according to internationally accepted criteria). Questionnaires assessing health status (SF-36, EQ-5D, EQ-VAS) and depressive symptoms (CES-D) were filled out. Health status and depressive symptoms were compared between patients with and without cognitive impairment. RESULTS: Patients with cognitive impairment (n=57) showed significantly lower scores on the physical and mental summary scores of the SF-36 than patients with normal cognition (difference: 3.5 (95%-CI 0.7-6.3, p=0.02, effect size 0.41) and 2.9 (95%-CI 0.3-5.6; p=0.03, effect size 0.37). EQ-5D index and EQ-VAS scores were significantly lower in patients with cognitive impairment. Depression (CES D>=16) occurred almost twice as often in patients with cognitive impairment (RR 1.8; 95%-CI: 1.1-3.0). CONCLUSIONS: Undiagnosed cognitive impairment in T2DM patients is associated with a reduced health status and more depressive symptoms. Detection of cognitive impairment in T2DM-patients identifies a vulnerable patient group that could benefit from tailored treatment and care. PMID- 26281971 TI - Non-invasive vascular assessment in the foot with diabetes: sensitivity and specificity of the ankle brachial index, toe brachial index and continuous wave Doppler for detecting peripheral arterial disease. AB - BACKGROUND & AIMS: Non-invasive lower limb vascular assessment in people at risk of peripheral arterial disease (PAD) including those with diabetes is crucial. There is evidence that standard assessment techniques such as the ankle-brachial index (ABI) may be less effective in people with diabetes. However there is limited evidence for other frequently used tests including continuous wave Doppler (CWD), and the toe-brachial index (TBI). The aim of this study was to determine the sensitivity and specificity of, ABI, CWD and TBI in a population with, and without diabetes. METHODS: Participants with and without diabetes who met current guidelines for vascular screening were recruited, and CWD waveforms, an ABI and a TBI were obtained from the right lower limb. Diagnostic accuracy was determined using colour duplex ultrasound (CFDU). Receiver operating characteristic curves were calculated. RESULTS: 117 participants were recruited, seventy-two with diabetes and forty-five without diabetes. CWD had the highest sensitivity in people with diabetes (74%) and without (84%). CWD also had the highest specificity in people with diabetes (74%) and without (84%) compared to both TBI and ABI. In participants with diabetes, the ABI was a poor test, area under the curve: 0.58 (p=0.27). CONCLUSIONS: CWD waveform is more likely to detect significant PAD compared to ABI and TBI in people with and without diabetes. PMID- 26281972 TI - Combination therapy with insulin glargine plus metformin but not insulin glargine plus sulfonylurea provides similar glycemic control to triple oral combination therapy in patients with type 2 diabetes uncontrolled with dual oral agent therapy. AB - AIMS: Evaluate substituting insulin glargine (GLAR) for a thiazolidinedione (TZD) versus adding a third oral antidiabetes drug (OAD) in patients with uncontrolled type 2 diabetes mellitus (T2DM) on TZD+metformin or TZD+sulfonylurea. METHODS: In this multicenter, open-label study, 337 T2DM patients with a glycated hemoglobin A1c (A1C) of 7.5-12.0% despite>=3months of treatment with a TZD plus metformin or a sulfonylurea were randomized to a third OAD (3OAD; metformin or glyburide) or GLAR+1 OAD (metformin or sulfonylurea) with TZD cessation, titrated to a fasting blood glucose<=94mg/dL. RESULTS: Substitution of GLAR for a TZD led to an adjusted mean A1C change from baseline of-1.66% versus-1.86% in the 3OAD arm (adjusted mean difference 0.20 [95% confidence interval, - 0.11, 0.51], not meeting the noninferiority criteria). This difference was driven by the GLAR+sulfonylurea stratum. GLAR+metformin was as effective as 3OAD in achieving glycemic control but with greater improvements in lipid parameters, less weight gain, and lower hypoglycemia rates. CONCLUSIONS: These findings favor substitution of GLAR for a TZD in T2DM patients not controlled on TZD+metformin. GLAR+sulfonylurea was less effective at lowering A1C than 3OAD and not associated with the benefits observed with GLAR+metformin. PMID- 26281974 TI - Zinc(II) and copper(II) complexes with hydroxypyrone iron chelators. AB - High stability of the complexes formed at physiological pH is one of the basic requisites that a good iron chelator must possess. At the same time the chelating agent must be selective toward iron, i.e., the stability of iron complexes must be significantly higher than that of the complexes formed with essential metal ions, in order that these last ones do not perturb iron chelation. In the frame of our research on iron chelators we have designed and synthesized a series of tetradentate derivatives of kojic acid, and examined their binding properties toward Fe(3+) and Al(3+). In this paper, for a characterization of the behavior of the proposed iron chelating agents in biological fluids, their complex formation equilibria with copper(II) and zinc(II) ions have been fully characterized together with a speciation study, showing the degree at which the iron chelators interfere with the homeostatic equilibria of these two essential metal ions. PMID- 26281973 TI - Behavior of the potential antitumor V(IV)O complexes formed by flavonoid ligands. 2. Characterization of sulfonate derivatives of quercetin and morin, interaction with the bioligands of the plasma and preliminary biotransformation studies. AB - The biotransformation in the plasma and red blood cells of two potential antitumor V(IV)O complexes formed by flavonoid ligands (quercetin or que and morin or mor) and their sulfonic derivatives (quercetin-5'-sulfonic acid or que(S) and morin-5'-sulfonic acid or mor(S)) was studied by spectroscopic (EPR, Electron Paramagnetic Resonance) and computational (DFT, Density Functional Theory) methods. Que and que(S) form with V(IV)O stable complexes, and in the systems with apo-transferrin (apo-hTf) and albumin (HSA) VO(que)2 and VO(que(S))2 remain unchanged. VO(mor)2 and VO(mor(S))2 undergo displacement reactions to give the partial formation of (VO)x(HSA) and (VO)(apo-hTf)/(VO)2(apo-hTf); moreover, mor(S) forms with apo-transferrin and albumin mixed species VO-mor(S)-apo-hTf and VO-mor(S)-HSA. In the systems with apo-hTf and HSA anisotropic EPR spectra at room temperature are detected in which the protein is not directly coordinated to V(IV)O(2+) ion. This is explained assuming that the bis-chelated complexes interact strongly with the proteins through a network of hydrogen bonds with the polar groups present on the protein surface. It is suggested that this "indirect" transport of V(IV)O species could be common to all the species containing ligands which can interact with the blood proteins. Uptake experiments by red blood cells were also carried out, using vanadium concentration of 5.0*10(-4)M and incubation time in the range 0-160min. VO(que)2/VO(que(S))2 and VO(mor)2/VO(mor(S))2 cross the erythrocytes membrane and in the cytosol VO(que)2/VO(que(S))2 do not transform, whereas VO(mor)2/VO(mor(S))2 give the partial formation of mixed species with hemoglobin (Hb) and other V(IV)O complexes. PMID- 26281975 TI - Integrative Utilization of Microenvironments, Biomaterials and Computational Techniques for Advanced Tissue Engineering. AB - This review aims to propose the integrative implementation of microfluidic devices, biomaterials, and computational methods that can lead to a significant progress in tissue engineering and regenerative medicine researches. Simultaneous implementation of multiple techniques can be very helpful in addressing biological processes. Providing controllable biochemical and biomechanical cues within artificial extracellular matrix similar to in vivo conditions is crucial in tissue engineering and regenerative medicine researches. Microfluidic devices provide precise spatial and temporal control over cell microenvironment. Moreover, generation of accurate and controllable spatial and temporal gradients of biochemical factors is attainable inside microdevices. Since biomaterials with tunable properties are a worthwhile option to construct artificial extracellular matrix, in vitro platforms that simultaneously utilize natural, synthetic, or engineered biomaterials inside microfluidic devices are phenomenally advantageous to experimental studies in the field of tissue engineering. Additionally, collaboration between experimental and computational methods is a useful way to predict and understand mechanisms responsible for complex biological phenomena. Computational results can be verified by using experimental platforms. Computational methods can also broaden the understanding of the mechanisms behind the biological phenomena observed during experiments. Furthermore, computational methods are powerful tools to optimize the fabrication of microfluidic devices and biomaterials with specific features. Here we present a succinct review of the benefits of microfluidic devices, biomaterial, and computational methods in the case of tissue engineering and regeneration medicine. Furthermore, some breakthroughs in biological phenomena including the neuronal axon development, cancerous cell migration and blood vessel formation via angiogenesis by virtue of the aforementioned approaches are discussed. PMID- 26281976 TI - beta-Lactoglobulin mutant Lys69Asn has attenuated IgE and increased retinol binding activity. AB - beta-Lactoglobulin (beta-LG) is a member of lipocalin superfamily of transporters for small hydrophobic molecules such as retinoids, fatty acids, drugs, and vitamins. beta-LG also is one of the major allergens in milk. Despite a lot of research on decreasing cow's milk allergenicity, the effects of mutations of beta LG on recognition by IgE from cow's milk allergy (CMA) patients have not been investigated. We describe here the expression in the yeast Pichia pastoris of a mutant bovine beta-LG, in which lysine at position 69, in the main epitopes of the protein, was changed into asparagine (Lys69Asn). The purity and native like folded structure of the recombinant Lys69Asn beta-LG was confirmed by HPLC, SDS PAGE, mass spectrometry and circular dichroism. Lys69Asn beta-LG has a fourfold stronger affinity than the wild-type protein for retinol, palmitic acid, and resveratrol, as determined by quenching of the intrinsic tryptophan fluorescence. At the same time the Lys69Asn mutant had a 9 fold attenuated, compared with the wild-type, affinity for IgE of sera from patients suffering from cow's milk allergy, whereas no difference could be detected between mutant and wild-type for binding of the IgGs of four monoclonal antibodies. The results of this study demonstrated the significant role of Lys69 residue on the binding and immuoreactivity properties of beta-LG. PMID- 26281978 TI - Management of Isolated Musculocutaneous Injury: Comparing Double Fascicular Nerve Transfer With Conventional Nerve Grafting. AB - PURPOSE: To compare the functional outcomes of nerve grafts and nerve transfers in the management of isolated musculocutaneous nerve (MCN) injuries. METHODS: We performed a retrospective case-control study of isolated MCN injury managed at a tertiary care center. The study group was composed of 12 patients managed with double nerve transfer whereas the 8 patients in the grafted group constituted the control group. RESULTS: In the study group, stab and missile injuries constituted most cases with a denervation period ranging between 3 and 9 months. Eleven patients in this group experienced a full range of active elbow flexion whereas one had antigravity flexion of 120 degrees . Electromyography revealed the first sign of reinnervation of biceps at 10 +/- 2 weeks, compared with 20 +/- 2 weeks in the grafted group. The overall trend was for patients in the study group to have earlier return of active elbow flexion and better restoration of elbow flexion strength and range of (presumably active) elbow motion than those treated with grafting, although none of these measures reached statistical significance. CONCLUSIONS: We found that distal nerve transfer was a superior method of managing isolated MCN injury compared with conventional nerve grafting. PMID- 26281977 TI - Pyrocarbon Metacarpophalangeal Joint Arthroplasty in Noninflammatory Arthritis: Minimum 5-Year Follow-Up. AB - PURPOSE: To report the outcomes, complications, and survivorship of pyrocarbon metacarpophalangeal joint arthroplasty in noninflammatory arthropathy at a minimum 5-year follow-up. METHODS: A retrospective review of 51 implants in 36 patients was undertaken. Patient demographics, complications, further surgery, and implant revision were recorded. Objective outcome was assessed by grip strength, range of motion, and radiological assessment of alignment, loosening, and subsidence. Subjective outcome was assessed by Patient Evaluation Measure, Quick Disabilities of the Arm, Shoulder and Hand score, and visual analog scores (0, best; 10, worst) for appearance, satisfaction, and pain. RESULTS: There were 35 index and 16 middle fingers. The average follow-up was 103 months (range, 60 172 months). The mean arc of motion was 54 degrees (range, 20 degrees to 80 degrees ). There was no difference in grip strength between operated and nonsurgical side. Six implants were revised, and 3 of these required additional surgery. The average Patient Evaluation Measure and Quick Disabilities of the Arm, Shoulder and Hand scores were 27 (range, 10-54) and 29 (range, 0-57), respectively. Mean visual analog scores for pain, satisfaction, and appearance were all 1 with the respective ranges being 0-7, 0-4, and 0-6. Most implants were Herren grade 1 lucency with the remaining 5 proximal and 12 distal implants being grade 2. Mean subsidence in the proximal component was 2 mm (range, 0-4 mm) and 1 mm (range, 0-3 mm) in the distal component. The degree of loosening or subsidence did not correlate with outcome. Implant survival as assessed by Kaplan-Meier was 88% at 10 years. CONCLUSIONS: Good pain relief, a functional range of motion, and high satisfaction were seen in the majority of patients. All implant revisions were performed within 18 months of the index procedure. This may represent technical issues rather than problems with the implant. PMID- 26281979 TI - The evolutionary conservation of rps3 introns and rps19-rps3-rpl16 gene cluster in Adiantum capillus-veneris mitochondria. AB - Ferns are a large and evolutionarily critical group of vascular land plants for which quite limited mitochondrial gene content and genome organization data are, currently, available. This study reports that the gene for the ribosomal protein S3 (rps3) is preserved and physically clustered to an upstream rps19 and a downstream overlapping rpl16 locus in the mitochondrial DNA of the true fern Adiantum capillus-veneris L. Sequence analysis also revealed that the rps3 gene is interrupted by two cis-splicing group II introns, like the counterpart in lycopod and gymnosperm representatives. A preliminary polymerase chain reaction (PCR) survey confirmed a scattered distribution pattern of both the rps3 introns also in other fern lineages. Northern blot and reverse transcription (RT)-PCR analyses demonstrated that the three ribosomal protein genes are co-transcribed as a polycistronic mRNA and modified by RNA editing. Particularly, the U-to-C type editing amends numerous genomic stop codons in the A. capillus-veneris rps19, rps3 and rpl16 sequences, thus, assuring the synthesis of complete and functional polypeptides. Collectively, the findings from this study further expand our knowledge of the mitochondrial rps3 architecture and evolution, also, bridging the significant molecular data gaps across the so far underrepresented ferns and all land plants. PMID- 26281980 TI - Age and pro-inflammatory gene polymorphisms influence adjacent segment disc degeneration more than fusion does in patients treated for chronic low back pain. AB - PURPOSE: Does lumbar fusion lead to accelerated adjacent segment disc degeneration (ASDD) or is it explained by genetics and aging? The influence of genetics on ASDD remains to be explored. This study assesses whether the disc space height adjacent to a fused segment is associated with candidate gene single nucleotide polymorphisms (SNPs). METHODS: Patients with low back pain from four RCTs (N = 208 fusion; 77 non-operative treatment) underwent standing plain radiography and genetic analyses at 13 +/- 4 years follow-up. Disc space height was measured using a validated computer-assisted distortion-compensated roentgen analysis technique and reported in standard deviations from normal values. Genetic association analyses included 34 SNPs in 25 structural, inflammatory, matrix degrading, apoptotic, vitamin D receptor and OA-related genes relevant to disc degeneration. These were analysed for their association with disc space height (after adjusting for age, gender, smoking, duration of follow-up and treatment group) first, separately, and then together in a stepwise multivariable model. RESULTS: Two SNPs from the IL18RAP gene (rs1420106 and rs917997) were each associated with a lower disc space height at the adjacent level (B = -0.34, p = 0.04 and B = -0.35, p = 0.04, respectively) and the MMP-9 gene SNP rs20544 was associated with a greater disc space height (B = 0.35, p = 0.04). Age (p < 0.001) and fusion (p < 0.008) were also significant variables in each analysis. The total explained variance in disc space height was for each SNP model 13-14 %, with 11-12 % of this being accounted for by the given SNP, 64-67 % by age and 19 22 % by fusion. In the multivariable regression analysis (with nine SNPs selected for entry, along with the covariates) the total explained variance in disc space height was 23 %, with the nine SNPs, age and fusion accounting for 45, 45 and 7 % of this, respectively. CONCLUSIONS: Age was the most significant determinant of adjacent segment disc space height followed by genetic factors, specifically inflammatory genes. Fusion explained a statistically significant but small proportion of the total variance. Much of the variance remained to be explained. PMID- 26281982 TI - The occurrence of vascular displacement into intervertebral disc space following the compensated sagittal imbalance of the spine: a case report and review of literature. AB - BACKGROUND: It is known that sagittal compensating mechanisms are created for counteracting sagittal imbalance problems; however, they can sometimes be associated with incidents which affect the plan of management. PURPOSE: The purpose of this study was to report a case of the occurrence of common iliac vessel displacement into the intervertebral disc space following one of the spinal compensatory mechanisms. MATERIAL AND METHODS: The authors demonstrated this case by showing the patient history, physical examination, imaging studies, and treatment strategy as well as by reviewing some related literature. RESULTS: An 81-year-old woman presented with a long history of low back pain with claudication. An upright plain radiograph and flexion-extension study demonstrated a progressive local thoracolumbar kyphosis and losing of lumbar lordosis with significant widening of the intervertebral disc space of L4-L5. An MRI scan and 3D volume rendering spiral computed tomography (3D-CT) revealed an abnormal content which was depicted as common iliac vessels inside the disc space of L4-L5. Consequently, a rare case of the occurrence of common iliac vessel displacement into the intervertebral disc space following one of the spinal compensatory mechanisms was reported. CONCLUSION: The occurrence of vascular displacement into the intervertebral disc space related to lumbar hyperextension, as a compensating mechanism, is a rare incident but can occur. Consequently, when this mechanism presents with abnormal widening of the intervertebral disc space, especially at the low lumbar level, it should raise surgeon's concern about the probability of vascular injury when performing a disc procedure. Thorough investigation with imaging studies and selecting the optimum surgical treatment are warranted. PMID- 26281981 TI - Prevalence of C5 nerve root palsy after cervical decompressive surgery: a meta analysis. AB - PURPOSE: To investigate the epidemiological prevalence of C5 palsy in patients following cervical decompressive surgery. METHODS: We searched the PUBMED database for relevant studies that mentioned the incidence of C5 palsy after cervical surgery. We also manually screened reference lists for additional qualified articles. Relevant prevalence estimates were calculated by an appropriate meta-analysis. Subgroup analysis, sensitivity analysis, and publication bias assessment were also performed, respectively. RESULTS: Finally, a total of 79 studies, with 704 C5 palsy cases in 13,621 patients, were included in our meta-analysis. The overall pooled prevalence of C5 palsy was 5.3% (95% CI 4.6-6.0%). Individuals after posterior cervical surgery (5.8%) had a slightly higher prevalence than those after anterior surgery (5.2%), and a similar trend was observed between ossification of posterior longitudinal ligament (OPLL) (5.8%) and cervical spondylotic myelopathy (CSM) (4.5%). The highest prevalence (11.0%) was found in patients who underwent laminectomy and fusion (LIF), while those who received anterior cervical discectomy and fusion (ACDF) had the lowest prevalence (3.3%). Other intermediate prevalence estimates increased gradually, from cervical laminoplasty-only (CLP-only) (5.1%), to CLP plus other posterior procedures (6.5%) and anterior cervical corpectomy and fusion (ACCF) (7.5%). The prevalence was significantly higher in male (5.2%) than in female (2.2%) patients. In most cases, C5 palsy was unilateral and transient, and diagnosed within 3 days (3.4%). CONCLUSION: Cervical surgery is associated with high risk of C5 palsy, particularly in patients who received LIF and in male patients. These figures may be useful in the estimation of the probability of C5 palsy following cervical surgery. PMID- 26281984 TI - Retraction Note to: Effect of NS-398, a cyclooxygenase-2 selective inhibitor, on the cytotoxicity of cytotoxic T lymphocytes to ovarian carcinoma cells. PMID- 26281985 TI - Retraction Note to: Comparison of hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and combined HCC-CC (CHC) with each other based on microarray dataset. PMID- 26281986 TI - Retraction Note to: Silencing of the Smad nuclear interacting protein 1 (SNIP1) by siRNA inhibits proliferation and induces apoptosis in pituitary adenoma cells. PMID- 26281983 TI - CRL4-DCAF1 ubiquitin E3 ligase directs protein phosphatase 2A degradation to control oocyte meiotic maturation. AB - Oocyte meiosis is a specialized cell cycle that gives rise to fertilizable haploid gametes and is precisely controlled in various dimensions. We recently found that E3 ubiquitin ligase CRL4 is required for female fertility by regulating DNA hydroxymethylation to maintain oocyte survival and to promote zygotic genome reprogramming. However, not all phenotypes of CRL4-deleted oocytes could be explained by this mechanism. Here we show that CRL4 controls oocyte meiotic maturation by proteasomal degradation of protein phosphatase 2A scaffold subunit, PP2A-A. Oocyte-specific deletion of DDB1 or DCAF1 (also called VPRBP) results in delayed meiotic resumption and failure to complete meiosis I along with PP2A-A accumulation. DCAF1 directly binds to and results in the poly ubiquitination of PP2A-A. Moreover, combined deletion of Ppp2r1a rescues the meiotic defects caused by DDB1/DCAF1 deficiency. These results provide in vivo evidence that CRL4-directed PP2A-A degradation is physiologically essential for regulating oocyte meiosis and female fertility. PMID- 26281987 TI - Retraction Note to: Promoter methylation of DAPK gene may contribute to the pathogenesis of nonsmall cell lung cancer: a meta-analysis. PMID- 26281988 TI - Retraction Note to: Relationship between VEGF protein expression and lymph node metastasis in papillary thyroid carcinoma among Asians: a meta-analysis. PMID- 26281989 TI - Retraction Note to: Correlations of IFN-gamma genetic polymorphisms with susceptibility to breast cancer: a meta-analysis. PMID- 26281990 TI - Retraction Note to: relationships between PTEN gene mutations and prognosis in glioma: a meta-analysis. PMID- 26281991 TI - Retraction Note to: Relationships between genetic polymorphisms in inflammation related factor gene and the pathogenesis of nasopharyngeal cancer. PMID- 26281993 TI - Retraction Note to: Aberrant promoter methylation of the CHD1 gene may contribute to the pathogenesis of breast cancer: a meta-analysis. PMID- 26281992 TI - Retraction Note to: Single-nucleotide polymorphisms of LIG1 associated with risk of lung cancer. PMID- 26281994 TI - Retraction Note to: Prognostic value of CD133 expression in cancer patients treated with chemoradiotherapy: a meta-analysis. PMID- 26281995 TI - Retraction Note to: Common polymorphism in the MMP-13 gene may contribute to the risk of human cancers: a meta-analysis. PMID- 26281996 TI - Retraction Note to: Relationship of serum MMP-7 levels for colorectal cancer: a meta-analysis. PMID- 26281997 TI - Retraction Note to: Correlation of IL-1F genetic polymorphisms with the risk of colorectal cancer among Chinese populations. PMID- 26281998 TI - Retraction Note to: A comprehensive analysis of candidate genes and pathways in pancreatic cancer. PMID- 26281999 TI - Retraction Note to: Identification of core miRNA based on small RNA-seq and RNA seq for colorectal cancer by bioinformatics. PMID- 26282000 TI - Hyperuricemia has an adverse impact on the prognosis of patients with osteosarcoma. AB - Patients with osteosarcoma have poor prognosis and are often at high risk of death. Identification of prognostic biomarkers for osteosarcoma may aid in improving the survival. Hyperuricemia had been suggested as a poor prognostic factor of several cancers, but the prognostic role of hyperuricemia in osteosarcoma patients had not been assessed. In the present study, we investigated the prognostic role of hyperuricemia at baseline on the overall survival of patients with osteosarcoma. Sixty osteosarcoma patients with hyperuricemia were matched (1:2) to 120 osteosarcoma patients without hyperuricemia with similar age and gender. Data from those patients with osteosarcoma were evaluated retrospectively. The role of hyperuricemia on overall survival was firstly analyzed using the Kaplan-Meier method. Univariate and multivariate Cox regression models were also used to further evaluate the prognostic significance of hyperuricemia. None of the clinicopathological parameters except distant metastasis was associated with hyperuricemia. Kaplan Meier method showed that patients with hyperuricemia had shorter overall survival compared with those with normouricemia (P < 0.0001, log-rank test). In univariate analysis, hyperuricemia was associated with poorer overall survival in osteosarcoma patients (HR = 2.71, 95 % CI 1.75-4.20; P < 0.0001). In the multivariate analysis, after adjusting for age, gender, serum alkaline phosphatase, stage, tumor size, and metastasis, hyperuricemia was independently associated with poorer overall survival in osteosarcoma patients (HR = 2.28, 95 % CI 1.41-3.69; P = 0.001). In conclusion, hyperuricemia at baseline is associated with poorer overall survival in osteosarcoma patients, and it has an adverse impact on the prognosis of osteosarcoma patients. PMID- 26282001 TI - MicroRNA-218 regulates cisplatin (DPP) chemosensitivity in non-small cell lung cancer by targeting RUNX2. AB - Downregulation of microRNA-218 (miR-218) is found in various human cancers, including non-small cell lung cancer (NSCLC). However, the involvement of chemosensitivity to cisplatin (DDP) and the underlying molecular mechanism remain unclear. In this study, we investigate whether miR-218 mediates NSCLC cell functions associated with chemoresistance. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect miR-218 expression in NSCLC cell lines A549/DDP and/or A549. The cell activity was measured by MTT assay. Cell cycle and cell apoptosis were detected by flow cytometry. Luciferase reporter assays and Western blots were used to validate runt-related transcription factor 2 (RUNX2) as a direct target gene of miR-218. miR-218 was significantly reduced in A549/DDP cells compared with parent A549 cells. Upregulation of miR-218 altered cell cycle-induced cell apoptosis and enhanced the sensitivity of A549/DDP cells to cisplatin. Mechanistically, RUNX2 was identified as a direct and functional target of miR-218, and RUNX2 executed the former on lung cancer chemoresistance. Our present study demonstrated for the first time that downregulation of miR-218 may contribute to the chemoresistance of NSCLC cells to cisplatin, which leads to upregulation of RUNX2. Uncovering the mechanism represents a novel approach to enhance the efficacy of chemotherapy during cancer treatment. PMID- 26282002 TI - Expression of eukaryotic translation initiation factor 5A-2 (eIF5A-2) associated with poor survival in gastric cancer. AB - Altered expression of eukaryotic translation initiation factor 5A-2 (eIF5A-2) was associated with human carcinogenesis and progression. This study assessed eIF5A-2 expression in gastric cancer tissues for association with clinicopathological parameters and survival of patients. A total of 436 gastric cancer tissues and 92 normal mucosal blocks were collected for construction of tissue microarrays and immunohistochemical assessment of eIF5A-2 expression. The data were statistically analyzed for association with clinicopathological factors and survival of patients. Immunohistochemical data showed that eIF5A-2 protein was highly expressed in gastric cancer tissues (p < 0.001). Upregulated expression of eIF5A 2 protein was associated with tumor Lauren classification, size, location, invasion, TNM stages, and lymph node and distant metastases. The 3- and 5-year cumulative survival rates of these 436 patients were 88.5 and 58.1 %, respectively. In contrast, the mean survival time of patients with increased tumor eIF5A-2 was 30.22 +/- 1.23 vs. 51.29 +/- 0.86 months for those with low tumor eIF5A-2 (p < 0.001). Multivariate analysis showed that eIF5A-2 expression and related tumor parameters were independent indicators of overall survival in gastric cancer patients. In conclusion, the current study indicates that overexpression of eIF5A-2 protein was associated with poor overall survival of gastric cancer patients. PMID- 26282003 TI - Antibody response to HER2 extracellular domain and subdomains in mouse following DNA immunization. AB - Human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-20 % of breast cancer patients and is an appropriate target for immunotherapy in these patients. Monoclonal antibodies (mAbs) specific to HER2 are currently applied to treat breast cancer patients with HER2 overexpression. Active immunization with HER2 DNA or protein has been considered as a suitable alternative. The aim of this study is to evaluate anti-HER2 antibody response in serum of mice immunized with DNA constructs containing full extracellular domain (fECD) or subdomains of human HER2. Four extracellular subdomains and also fECD of HER2 were cloned into pCMV6-Neo vector. Different groups of Balb/C mice were immunized with HER2 DNA constructs and boosted with HER2 recombinant protein. The anti-HER2 antibody was subsequently determined by ELISA, flow cytometry, and immunohistochemistry. Anti HER2 antibody was detected only in serum of mice immunized with fECD DNA. None of HER2 extracellular subdomains induced appreciable levels of anti-HER2 antibody. However, boosting with fECD or extracellular subdomain III (DIII) recombinant protein resulted in enhanced anti-HER2 fECD as well as anti-HER2 subdomain antibody responses. In this regard, almost all (99 %) of HER2-overexpressing BT474 cells could be detected by serum antibody from mice immunized with HER2 subdomain DNA and boosted with recombinant HER2 protein by flow cytometry. Similarly, serum of mice immunized with DIII DNA construct and boosted with recombinant DIII protein could also recognize these cells, but to a lesser extent (50 %). Our findings suggest that combination of HER2 DNA and protein immunization could effectively induce anti-HER2 antibody response in Balb/C mice. PMID- 26282004 TI - AdipoRon: a possible drug for colorectal cancer prevention? AB - Colorectal cancer (CRC) is in the third place of the most common cancers. Certain risk factors can increase the development of CRC, including diet and inheritance. Several studies have shown that there is a potential link between obesity and CRC. Adipose tissue is known to be a largest endocrine organ in the body, with the ability to produce various cytokines including adiponectin. Two types of adiponectin receptor, AdipoR1 and AdipoR2, have been detected in various cancer tissues such as CRC. There is mounting evidence that AdipoR1 signaling occurs mainly through 5' AMP-activated protein kinase (AMPK) and adiponectin inhibits colorectal cancer cell growth via activation of AMPK, thereby suppression of the mammalian target of rapamycin (mTOR) pathway. Thus, adiponectin replacement-based therapies may represent a novel approach in CRC cell growth inhibition in early stages. AdipoRon is an adiponectin-like synthetic small molecule that activated both adiponectin receptors 1 and 2. We hypothesize that AdipoRon has antiproliferative effects of adiponectin and may suppress the CRC cell growth. With clarification of this drug's role in CRC, it can be used as chemoprevention in patients at risk of developing the disease. PMID- 26282005 TI - Prognostic value of long noncoding RNA MALAT1 in various carcinomas: evidence from nine studies. AB - RNA-sequencing technology is progressing day by day. Numerous researches have showed that long noncoding RNAs (lncRNAs) play oncogenic or tumor suppressor roles in tumor biological processes. To our knowledge, many studies have identified a lot of lncRNAs with aberrant expression in several types of cancers. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a newly discovered lncRNA, has been reported that is overexpressed in several types of cancers. But the clinical value of MALAT1 in cancers remains unclear. Therefore, in this present study, we aimed to investigate potential clinical application role of MALAT1 as a prognostic biomarker in malignant tumors. We performed a detailed search in PubMed, Embase, Medline, and Cochrane Library until July 2015. According to the inclusion and exclusion criteria, nine studies with a total of 941 patients were selected to explore the relationship between high expression of MALAT1 and overall survival in cancers. The result showed that overexpression of MALAT1 could predict poor overall survival (OS) in cancer patients, with pooled hazard ratio (HR) of 1.90 [95 % confidence interval (CI) 1.68-2.16, P < 0.0001]. In conclusion, the present meta-analysis demonstrated that high expression of MALAT1 might be served as a novel prognostic biomarker in different types of cancers. PMID- 26282006 TI - The effectiveness of a preventive health program and vitamin D status in improving health-related quality of life of older Canadians. AB - PURPOSE: To assess the effectiveness of a preventive health program and vitamin D status in improving the health-related quality of life (HRQOL) of older residents of Canada. DESIGN: We analyzed baseline and follow-up data of 2119 volunteers of a community program that promotes healthy lifestyles and encourages vitamin D supplementation. We examined the program effect on each of the five dimensions of the EQ-5D-5L, HRQOL score, and quality-adjusted life years (QALYs) using multivariable regression methods. We further examined the specific contribution of vitamin D status as quantified by serum 25-hydroxyvitamin D (25(OH)D). RESULTS: Problems with mobility, usual activities, pain/discomfort, and depression/anxiety were reported less during follow-up compared to baseline. On average, participants' HRQOL had improved by 0.018 units at 6 months and 0.025 units at 1 year of follow-up. Improvements in vitamin D status were independently associated with improvements in HRQOL and in QALYs. As per 25 nmol/L increase in 25(OH)D, there was a 0.002 increase in HRQOL and a 0.001 increase in QALYs. CONCLUSIONS: This study documents the benefits of a real-world preventive health program to HRQOL. It is the first to reveal that improvements in vitamin D status parallel improvements in HRQOL among healthy community dwellers. The study further suggests that the preventive health program and supplementation with vitamin D are cost-effective interventions. PMID- 26282007 TI - Dimensionality of the Center for Epidemiologic Studies Depression Scale: an exploratory bi-factor analytic study. AB - OBJECTIVE: The Center for Epidemiologic Studies Depression Scale (CES-D) is a widely used instrument for measuring depressive symptoms. Though conventional factor analytic evaluations supported the use of four sub-scales for the CES-D, existing studies have yet to adopt the bi-factor analytic approach in psychometric assessment of the 20-item inventory. The present study aimed to apply both confirmatory factor analysis and exploratory bi-factor analysis to evaluate the dimensionality of the CES-D. METHODS: Current scoring practice of the CES-D (single-factor, four-factor, and second-order models) was tested using confirmatory factor analyses in a sample of 706 Chinese persons with insomnia and depressive symptoms. As an alternative, exploratory bi-factor analysis was conducted to examine the utility of the general depression factor and specific factors. RESULTS: Existing measurement models on the CES-D did not provide an adequate model fit to the data in terms of model fit indices and discriminant validity. The bi-factor model revealed a general depression factor that accounted for the majority of the item variance. The three specific factors (somatic symptoms, positive affect, and interpersonal problems) provided little unique information over and above the general factor and plausibly represent a methodological artifact rather than a substantive factor. CONCLUSION: The present study demonstrated empirical support for the bi-factor model as a realistic representation of the underlying structure of the CES-D. Researchers and clinicians are better served by simply using a single measure of depression. PMID- 26282008 TI - Optimization of the monitoring network on the River Tisza (Central Europe, Hungary) using combined cluster and discriminant analysis, taking seasonality into account. AB - The most essential requirement for water management is efficient and informative monitoring. Operating water quality monitoring networks is a challenge from both the scientific and economic points of view, especially in the case of river sections ranging over hundreds of kilometers. Therefore, spatio-temporal optimization is vital. In the present study, the optimization of the monitoring system of the River Tisza, the second largest river in Central Europe, is presented using a generally applicable and novel method, combined cluster and discriminant analysis (CCDA). This area for the study was chosen because, spatial inhomogeneity of a river's monitoring network can more easily be studied in a mostly natural watershed - as in the case of the River Tisza - since the effects of man-made obstacles: e.g water barrage systems, hydroelectric power plants, artificial lakes, etc. are more pronounced. Furthermore, since the temporal sampling frequency was bi-weekly, the opportunity of optimizing the monitoring system on a temporal (monthly) scale arose. In the research, 15 water quality parameters measured at 14 sampling sites in the Hungarian section of the River Tisza were assessed for the time period 1975-2005. First, four within-year sections ("hydrochemical seasons") were determined, characterized with unequal lengths, namely 2, 4, 2, and 4 months long starting with spring. Homogeneous groups of sampling sites were determined in space for every season, with the main separating factors being the tributaries and man-made obstacles. Similarly, an overall pattern of homogeneity was determined. As an overall result, the 14 sampling sites could be grouped into 11 homogeneous groups leading to the possibility of reducing the number of sampling locations and thus making the monitoring system more cost-efficient. PMID- 26282009 TI - Molecular study of Stenoponia tripectinata tripectinata (Siphonaptera: Ctenophthalmidae: Stenoponiinae) from the Canary Islands: taxonomy and phylogeny. AB - In the present work, we carried out a comparative molecular study of Stenoponia tripectinata tripectinata isolated from Mus musculus from the Canary Islands, Spain. The Internal Transcribed Spacers 1 and 2 (ITS1, ITS2) and 18S ribosomal RNA partial gene and cytochrome c-oxidase 1 (cox1) mitochondrial DNA partial gene sequences of this subspecies were determined to clarify the taxonomic status of this subspecies and to assess inter-population variation and inter-specific sequence differences. In addition, we have carried out a comparative phylogenetic study with other species of fleas using Bayesian, Maximum Parsimony, Maximum Likelihood and Neighbor-Joining analysis. A geographical signal was detected between the cox1 partial gene sequences of S. t. tripectinata isolated from M. musculus from different islands and those isolated from Apodemus sylvaticus from the Iberian Peninsula. Our results assess the monophyletic origin of Stenoponiinae and a different genetic lineage from Ctenophthalmidae. Thus, the elevation of subfamily Stenoponiinae to family level (Stenoponiidae) is suggested. PMID- 26282010 TI - Solid-state structure, solution-state behaviour and catalytic activity of electronically divergent C,N-chelating palladium-N-heterocyclic carbene complexes. AB - A family of electronically diverse pyridyl- and picolyl-substituted imidazolium salts have been prepared and coordinated to palladium in a single step, to deliver a variety of palladium(ii)-N-heterocyclic carbene (NHC) complexes. Neutral Pd(NHC)X2, cationic [Pd(NHC)2X]X and dicationic [Pd(NHC)2]X2-type complexes have been isolated and fully characterised, with single-crystal X-ray analysis revealing a variety of coordination environments around the palladium centres. The pre-formed complexes have been employed in a model Suzuki-Miyaura cross-coupling reaction to yield a sterically congested tetra-ortho-substituted biaryl product, showcasing turnover numbers comparable to Pd-PEPPSI-IPr catalyst. PMID- 26282012 TI - The shifting conceptualization of elder abuse in the United States: from social services, to criminal justice, and beyond. PMID- 26282013 TI - Guiding pancreatic beta cells to target electrodes in a whole-cell biosensor for diabetes. AB - We are developing a cell-based bioelectronic glucose sensor that exploits the multi-parametric sensing ability of pancreatic islet cells for the treatment of diabetes. These cells sense changes in the concentration of glucose and physiological hormones and immediately react by generating electrical signals. In our sensor, signals from multiple cells are recorded as field potentials by a micro-electrode array (MEA). Thus, cell response to various factors can be assessed rapidly and with high throughput. However, signal quality and consequently overall sensor performance rely critically on close cell-electrode proximity. Therefore, we present here a non-invasive method of further exploiting the electrical properties of these cells to guide them towards multiple micro electrodes via electrophoresis. Parameters were optimized by measuring the cell's zeta potential and modeling the electric field distribution. Clonal and primary mouse or human beta-cells migrated directly to target electrodes during the application of a 1 V potential between MEA electrodes for 3 minutes. The morphology, insulin secretion, and electrophysiological characteristics were not altered compared to controls. Thus, cell manipulation on standard MEAs was achieved without introducing any external components and while maintaining the performance of the biosensor. Since the analysis of the cells' electrical activity was performed in real time via on-chip recording and processing, this work demonstrates that our biosensor is operational from the first step of electrically guiding cells to the final step of automatic recognition. Our favorable results with pancreatic islets, which are highly sensitive and fragile cells, are encouraging for the extension of this technique to other cell types and microarray devices. PMID- 26282014 TI - Homeostatic regulation in physiological systems: A versatile Ansatz. AB - A generic modelling formalism is described for homeostatic dynamics in physiological systems. The method is particularly suited where the peripheral, physiological system itself is well-characterised, but the details of the central, regulatory component (the nervous and endocrine systems) have not necessarily been characterised in full detail. The method is applied to temperature regulation in Cardinalis cardinalis, C. sinuatus, Lepus alleni, and Passer domesticus, and furthermore to hydromineral regulation in Lymnaea stagnalis. These case studies demonstrate that the method allows a comprehensive analysis and integration of the available data and is capable of furnishing physiologically relevant predictions. We discuss the method in relation to optimal control theory as well as more conventional modelling approaches. PMID- 26282015 TI - Effectiveness of an audience response system on orthodontic knowledge retention of undergraduate dental students--a randomised control trial. AB - OBJECTIVE: To determine the effect of an audience response system (ARS) on knowledge retention of dental students and to gauge student perceptions of using the ARS. DESIGN: Randomised control study. SETTING: School of Dentistry, Cardiff University. PARTICIPANTS: Seventy four second-year dental students were stratified by gender and randomised anonymously to one of two groups. METHODS: One group received a lecture on orthodontic terminology and diagnosis in a traditional didactic format and the other received the same lecture integrated with ARS slides. Students completed an assessment of multiple-choice questions (MCQs) scored out of 20, before and immediately after the lecture. Students were also asked to complete a self-reported questionnaire on their perceptions of ARS. RESULTS: Both groups had statistically significant increases in MCQ scores post lecture (ARS mean increase 3.6 SD2.0, 95% CI 2.2-3.5 and Didactic mean increase 2.9 SD2.3, 95% CI 2.8-4.3). A mixed-design analysis of variance showed that ARS led to an improved MCQ score (by 0.8 or 25%) compared to the didactic group, although this effect was not significant (P = 0.15). The effect of gender at baseline (P = 0.49), post-lecture (P = 0.73) and increase in MCQ score split by group (P = 0.46) was also not significant. Students reported that the ARS was easy to use, helped them engage with the lecture and encouraged them to work harder. CONCLUSION: The ARS did not lead to a significant increase in short-term orthodontic knowledge recall of students compared with didactic teaching. However, the use of ARS within orthodontic teaching could make lectures more interactive and engaging. PMID- 26282016 TI - Art, architecture, and the molecular frontier. PMID- 26282017 TI - Reply: To PMID 26123517. PMID- 26282018 TI - Editorial Comment. PMID- 26282019 TI - Editorial Comment. PMID- 26282020 TI - Correction to "Engineered CuInSexS2-x Quantum Dots for Sensitized Solar Cells". PMID- 26282021 TI - Mechanisms of Morphological Evolution of Li2O2 Particles during Electrochemical Growth. AB - Li-O2 batteries, wherein solid Li2O2 is formed at the porous air cathode during discharge, are candidates for high gravimetric energy (3212 Wh/kgLi2O2) storage for electric vehicles. Understanding and controlling the nucleation and morphological evolution of Li2O2 particles upon discharge is key to achieving high volumetric energy densities. Scanning and transmission electron microscopy were used to characterize the discharge product formed in Li-O2 batteries on electrodes composed of carpets of aligned carbon nanotubes. At low discharge rates, Li2O2 particles form first as stacked thin plates, ~10 nm in thickness, which spontaneously splay so that secondary nucleation of new plates eventually leads to the development of a particle with a toroidal shape. Li2O2 crystallites have large (001) crystal faces consistent with the theoretical Wulff shape and appear to grow by a layer-by-layer mechanism. In contrast, at high discharge rates, copious nucleation of equiaxed Li2O2 particles precedes growth of discs and toroids. PMID- 26282022 TI - Mapping the Relation between Stacking Geometries and Singlet Fission Yield in a Class of Organic Crystals. AB - By generating two free charge carriers from a single high-energy photon, singlet fission (SF) promises to significantly improve the efficiency of a class of organic photovoltaics (OPVs). However, SF is generally a very inefficient process with only a small number of absorbed photons successfully converting into triplet states. In this Letter, we map the relation between stacking geometry and SF yield in crystals based on perylenediimide (PDI) derivatives. This structure function analysis provides a potential explanation for the SF yield discrepancies observed among similar molecular crystals and may help to identify favorable geometries that lead to an optimal SF yield. Exploring the subtle relationship between stacking geometry and SF yield, this Letter suggests using crystal structure engineering to improve the design of SF-based OPVs. PMID- 26282023 TI - Understanding Plasmonic Properties in Metallic Nanostructures by Correlating Photonic and Electronic Excitations. AB - A large number of optical phenomena rely on the excitation of localized surface plasmon resonances (LSPR) in metallic nanostructures. Electron-energy loss spectroscopy (EELS) in a scanning transmission electron microscope (STEM) has emerged as a technique capable of mapping plasmonic properties on length scales 100 times smaller than optical wavelengths. While this technique is promising, the connection between electron-driven plasmons, encountered in EELS, and photon driven plasmons, encountered in plasmonic devices, is not well understood. This Perspective highlights some of the contributions that have been made in correlating optical scattering and STEM/EELS from the exact same nanostructures. The experimental observations are further elucidated by comparison with theoretical calculations obtained from the electron-driven discrete dipole approximation, which provides a method to calculate EEL spectra for nanoparticles of arbitrary shape. Applications of plasmon mapping to the electromagnetic hot spots encountered in single-molecule surface-enhanced Raman scattering and electron beam induced damage in silver nanocubes are discussed. It is anticipated that the complementarity of both techniques will address issues in fundamental and applied plasmonics going forward. PMID- 26282024 TI - b2 Peaks in SERS Spectra of 4-Aminobenzenethiol: A Photochemical Artifact or a Real Chemical Enhancement? AB - Strong b2 peaks (1142, 1391, 1438, and 1583 cm(-1)) in the SERS spectra of 4 aminobenzenethiol (ABT) have been regarded by many as a textbook example of chemically enhanced SERS signals. However, this interpretation is in serious doubt after the recent claim that they arise from 4,4'-dimercaptoazobenzenes (DMAB) photogenerated during the acquisition of SERS, not the genuine chemically enhanced signals of ABT. Subsequent attempts to prove or disprove this claim have failed to provide any decisive verdict. Here we present spectroscopic and mass spectrometric evidence that further support the photogeneration of DMABs from ABTs on an Ag surface. Furthermore, we show that the amount of the DMAB is sufficient to explain the b2 intensities of ABT. PMID- 26282025 TI - Electron Conduction and Photocurrent Generation of a Light-Harvesting/Reaction Center Core Complex in Lipid Membrane Environments. AB - To reveal the structure-function relationship of membrane proteins, a membrane environment is often used to establish a suitable platform for assembly, functioning, and measurements. The control of the orientation of membrane proteins is the main challenge. In this study, the electron conductivity and photocurrent of a light-harvesting/reaction center core complex (LH1-RC) embedded in a lipid membrane were measured using conductive atomic force microscopy (C AFM) and photoelectrochemical analysis. AFM topographs showed that LH1-RC molecules were well-orientated, with their H-subunits toward the membrane surface. Rectified conductivity was observed in LH1-RC under precise control of the applied force on the probe electrode (<600 pN). LH1-RC embedded in a membrane generated photocurrent upon irradiation when assembled on an electrode. The observed action spectrum was consistent with the absorption spectrum of LH1-RC. The control of the orientation of LH1-RC by lipid membranes provided well-defined conductivity and photocurrent. PMID- 26282026 TI - Molecular Orbitals Strictly Localized on Small Molecular Fragments from X-ray Diffraction Data. AB - Nowadays, the electron density is recognized as a fundamental property that contains most of the information concerning the electronic structure of molecules, and, therefore, its determination from high-resolution X-ray diffraction data is becoming more and more important. In this context, we propose a new strategy for the charge density analysis, strategy in which the chemical interpretability of the multipole model is combined with the quantum mechanical rigor of the wave function-based approaches. In particular, this novel technique aims at extracting molecular orbitals strictly localized on small molecular fragments (e.g., atoms, bonds, or functional groups) from a set of measured structure factors amplitudes. Preliminary tests have shown that their determination is really straightforward and, given their reliable transferability, we envisage the possibility of constructing new extremely localized molecular orbital databases as an alternative to the existing pseudoatom libraries. PMID- 26282027 TI - No Graphene Etching in Purified Hydrogen. AB - A systematic study has been conducted to investigate the role of hydrogen in the etching reaction of graphene films grown on copper foils. The results at 825 degrees C and 500 mTorr showed no evidence of graphene etching by purified ultrahigh purity (UHP)-grade hydrogen, whereas graphene films exposed to unpurified UHP-grade hydrogen were considerably etched due to the presence of oxygen or other oxidizing impurities. This finding reveals not only the major impact of oxidizing impurities in the graphene etching reaction, but also entails understanding and controlling the graphene chemical vapor deposition mechanism on copper substrates. PMID- 26282028 TI - IR Spectra of the Water Hexamer: Theory, with Inclusion of the Monomer Bend Overtone, and Experiment Are in Agreement. AB - Signature IR spectra of isomers of the water hexamer in the spectral range 3000 3800 cm(-1) have been reported by experimentalists, but crucial theoretical interpretation has still not been definitive. Using ab initio potential and dipole moment surfaces and a fully coupled quantum treatment of the intramolecular modes, the ring and book are assigned to spectra obtained in the He nanodroplet and Ar tagging experiments, respectively. The overtone of the intramolecular bend at ca. 3200 cm(-1) is a new calculated feature that completes an important missing piece in previous experimental and theoretical comparisons and leads to a consistent assignment of these two experimental spectra. Calculated IR spectra for the lowest energy forms of the water heptamer and octomer are also presented and compared to experiment. In all the calculated spectra, the bend overtone is demonstrated to be a noticeable feature, and this is one important conclusion from the work. Also, the danger in using scaled double-harmonic spectra to assign spectra is demonstrated. PMID- 26282029 TI - Probing the Structure-Property Interplay of Plasmonic Nanoparticle Transducers Using Femtosecond Laser Spectroscopy. AB - The characteristic feature of noble metal nanoparticles is the localized surface plasmon resonance (LSPR). Plasmon-supporting nanoparticles can function as transducers because of the LSPR's ability to amplify electromagnetic fields and its sensitivity to changes in the surrounding dielectric. The performance of these materials in transducer applications is inherently related to nanoparticle structure. This Perspective describes the use of femtosecond laser-based spectroscopies to elucidate the nanoscale structure-property interplay. First, femtosecond time-resolved transient extinction measurements that probe the LSPR following nanoparticle photoexcitation are described. These measurements illustrate how nanostructure dimensions influence sensitivity to changes in the interfacial dielectric. The combination of single-particle nonlinear optical (NLO) measurements and electron microscopy is also used to describe the symmetry of plasmon surface fields in nanoparticle assemblies. In particular, the use of continuous polarization variation-detected second-harmonic generation to describe electric and magnetic dipolar contributions to NLO properties is discussed. PMID- 26282030 TI - Two-Dimensional Hexagonal Transition-Metal Oxide for Spintronics. AB - Two-dimensional materials have been the hot subject of studies due to their great potential in applications. However, their applications in spintronics have been blocked by the difficulty in producing ordered spin structures in 2D structures. Here we demonstrated that the ultrathin films of recently experimentally realized wurtzite MnO can automatically transform into a stable graphitic structure with ordered spin arrangement via density functional calculation, and the stability of graphitic structure can be enhanced by external strain. Moreover, the antiferromagnetic ordering of graphitic MnO single layer can be switched into half-metallic ferromagnetism by small hole-doping, and the estimated Curie temperature is higher than 300 K. Thus, our results highlight a promising way toward 2D magnetic materials. PMID- 26282031 TI - Carbon Nanotube-Patterned Surface-Based Recognition of Carcinoembryonic Antigens in Tumor Cells for Cancer Diagnosis. AB - It has been of high significance to devise a biochemical analytical tool kit enabling the detection of few circulating tumor cells (CTCs) for early diagnosis of cancer. Despite recent effort made to detect few CTCs, it is still challenging to sense such cells with their low concentration and/or the minute amount of marker proteins expressed on few CTCs. In this work, we report the label-free recognition of carcinoembryonic antigens (CEAs) expressed on few CTCs by using a carbon nanotube (CNT) sensor coupled with scanning probe microscopy imaging for cancer diagnosis. It is shown that a CNT-patterned surface is able to specifically capture the CEA molecules in the whole cell lysate of CTCs with their concentration even up to 10(-3) cells/mL. Our work sheds light on our bioassay based on a CNT-patterned surface for highly sensitive, label-free detection of marker proteins expressed on few tumor cells, which may open a new avenue in early diagnosis of cancer by providing a novel biochemical analysis tool kit. PMID- 26282032 TI - Local Ionization Dynamics Traced by Photoassisted Scanning Tunneling Microscopy: A Theoretical Approach. AB - For tracing the spatiotemporal evolution of electronic systems, we suggest and analyze theoretically a setup that exploits the excellent spatial resolution based on scanning tunneling microscopy techniques combined with the temporal resolution of femtosecond pump-probe photoelectron spectroscopy. As an example, we consider the laser-induced, local vibrational dynamics of a surface-adsorbed molecule. The photoelectrons released by a laser pulse can be collected by the scanning tip and utilized to access the spatiotemporal dynamics. Our proof-of principle calculations are based on the solution of the time-dependent Schrodinger equation supported by the ab initio computation of the matrix elements determining the dynamics. PMID- 26282033 TI - Nanoscale Morphology of Water in Silica Colloidal Crystals. AB - We show a simple method to visualize the morphology of water adsorbed within the pore network of colloidal crystals made of submicrometer silica spheres. Water is replicated into silica by modified silicon tetrachloride hydrolysation under standard ambient conditions, making it visible to standard electronic microscopy and thus allowing one to discern the original water distribution. Different distribution patterns are identified depending on the water content, surface condition, and spheres arrangement. The dimension and shape of wetting layers (covering the submicrometer spheres) and capillary bridges (joining them) are measurable at the nanoscale. We finally use these findings to demonstrate proof of-principle of fabrication of isolated and freestanding silica nanorings by using hydrophobic polymeric templates and selective etching. PMID- 26282034 TI - Inelastic Neutron Scattering Investigation in Glassy SiSe2: Complex Dynamics at the Atomic Scale. AB - A detailed investigation of the THz dynamics in glassy SiSe2 by means of neutron inelastic scattering is presented. To carefully map the translational dynamics and the region of the boson peak, we carried out two different experiments with sharp and broad resolutions coupled with a narrow and a wide kinematic range, respectively. Data show a complex pattern of excitations made up of three components. The most intense one is the prolongation of the longitudinal acoustic mode while two other modes appear in the boson peak region below 3 meV. We propose an interaction model that allows for a consistent identification of the nature of these modes. PMID- 26282035 TI - Aberration-Corrected TEM Imaging of Oxygen Occupancy in YSZ. AB - We present atomic-scale imaging of oxygen columns and show quantitative analysis on the occupancy of the columns in yttria-stabilized zirconia (YSZ) using aberration-corrected TEM operated under the negative Cs condition. Also, individual contributions both from oxygen column occupancy and the static displacement of oxygen atoms due to occupancy change to the observed column intensities of TEM images were systematically investigated using HRTEM simulation. We found that oxygen column intensity is governed primarily by column occupancy rather than by static displacement of oxygen atoms. Utilizing the aberration-corrected TEM capability and HRTEM simulation results, we experimentally verified that oxygen vacancies segregate near the single grain boundary of a YSZ bicrystal. The methodology and the high spatial resolution characterization tool employed in the present study provide insights into the distribution of oxygen vacancies in the bulk as well as near grain boundaries and pave the way for further investigation and atomic-scale analysis in other important oxide materials. PMID- 26282036 TI - Transition-Metal Nanoparticle Oxidation in a Chemically Nonhomogenous Environment Revealed by 2p3d Resonant X-ray Emission. AB - X-ray absorption spectroscopy (XAS) is often employed in fields such as catalysis to determine whether transition-metal nanoparticles are oxidized. Here we show 2p3/2 XAS and 2p3d resonant X-ray emission spectroscopy (RXES) data of oleate coated cobalt nanoparticles with average diameters of 4.0, 4.2, 5.0, 8.4, and 15.2 nm. Two particle batches were exposed to air for different periods of time, whereas the others were measured as synthesized. In the colloidal nanoparticles, the cobalt sites can have different chemical environments (metallic/oxidized/surface-coordinated), and it is shown that most XAS data cannot distinguish whether the nanoparticles are oxidized or surface-coated. In contrast, the high-energy resolution RXES spectra reveal whether more than the first metal layer is oxidized based on the unique energetic separation of spectral features related to the formal metal (X-ray fluorescence) or to a metal oxide (d-d excitations). This is the first demonstration of metal 2p3d RXES as a novel surface science tool. PMID- 26282037 TI - Single-Molecule Surface-Enhanced Raman Scattering Sensitivity of Ag-Core Au-Shell Nanoparticles: Revealed by Bi-Analyte Method. AB - Single-molecule surface-enhanced Raman scattering (SM-SERS) is an important application of localized surface plasmons in metallic nanostructures. Conventionally, Ag nanoparticles are used in solution-based SM-SERS experiments, but their usage is limited due to toxicity and oxidation issues. Au nanoparticle solutions are relatively biocompatible and SERS-active, but they do not facilitate large-scale SERS enhancement factors, which is an important prerequisite for SM-SERS. Under such constraints, silver-core gold-shell nanoparticles can be an excellent alternative for SM-SERS. Motivated by this, herein we report on the experimental evidence of SM-SERS sensitivity of Ag-core Au-shell nanoparticles by employing bianalyte method. Additionally, by detecting resonant molecules at femtomolar concentrations, we show that Ag-core Au-shell nanoparticle can be harnessed for ultrasensitive detection of molecules. The provided evidence will further motivate usage of such gold-shell-based bimetallic nanostructures for SM-SERS in biological environments. PMID- 26282038 TI - Expeditious Stochastic Calculation of Random-Phase Approximation Energies for Thousands of Electrons in Three Dimensions. AB - A fast method is developed for calculating the random phase approximation (RPA) correlation energy for density functional theory. The correlation energy is given by a trace over a projected RPA response matrix, and the trace is taken by a stochastic approach using random perturbation vectors. For a fixed statistical error in the total energy per electron, the method scales, at most, quadratically with the system size; however, in practice, due to self-averaging, it requires less statistical sampling as the system grows, and the performance is close to linear scaling. We demonstrate the method by calculating the RPA correlation energy for cadmium selenide and silicon nanocrystals with over 1500 electrons. We find that the RPA correlation energies per electron are largely independent of the nanocrystal size. In addition, we show that a correlated sampling technique enables calculation of the energy difference between two slightly distorted configurations with scaling and a statistical error similar to that of the total energy per electron. PMID- 26282039 TI - Can Surface Plasmon Fields Provide a New Way to Photosensitize Organic Photoreactions? From Designer Nanoparticles to Custom Applications. AB - In this Perspective, we explore the opportunities that plasmon excitation may offer for the practitioners in organic chemistry. Beyond the interesting physical properties and lively colors of colloidal solutions of noble metal nanostructures, excitation of plasmon transitions can trigger a variety of processes, from the simple heat delivery with pinpoint precision, to the enhanced generation of excited states in the immediate vicinity of the nanoparticle, to electron- and hole-transfer processes that can readily participate in photoredox processes. In understanding how particles are produced, what properties they have, and the diversity of nanostructures and environments in which they can be produced, we aim at providing the small steps toward a paradigm that will allow organic chemists to take advantage of the opportunities that await in the area of plasmon-assisted processes. PMID- 26282040 TI - More Is Different: Experimental Results on the Effect of Biomolecules on the Dynamics of Hydration Water. AB - Biological interfaces characterized by a complex mixture of hydrophobic, hydrophilic, or charged moieties interfere with the cooperative rearrangement of the hydrogen-bond network of water. In the present study, this solute-induced dynamical perturbation is investigated by extended frequency range depolarized light scattering experiments on an aqueous solution of a variety of systems of different nature and complexity such as small hydrophobic and hydrophilic molecules, amino acids, dipeptides, and proteins. Our results suggest that a reductionist approach is not adequate to describe the rearrangement of hydration water because a significant increase of the dynamical retardation and extension of the perturbation occurs when increasing the chemical complexity of the solute. PMID- 26282041 TI - Plasmonics. Electron Oscillations and Beyond. PMID- 26282042 TI - Dispersive Electronic States of the pi-Orbitals Stacking in Single Molecular Lines on the Si(001)-(2*1)-H Surface. AB - One-dimensional (1D) molecular assemblies have been considered as one of the potential candidates for miniaturized electronic circuits in organic electronics. Here, we present the quantitative experimental measurements of the dispersive electronic feature of 1D benzophenone molecular assemblies on the Si(001)-(2*1) H. The well-aligned molecular lines and their certain electronic state dispersion were observed by scanning tunneling microscopy (STM) and angle-resolved ultraviolet photoemission spectroscopy (ARUPS), respectively. Density functional theory (DFT) calculations reproduced not only the experimental STM image but also the dispersive features that originated from the stacking phenyl pi-orbitals in the molecular assembly. We obtained the effective mass of 2.0me for the hole carrier along the dispersive electronic state, which was comparable to those of the single-crystal molecules widely used in organic electronic applications. These results ensure the one-dimensionally delocalized electronic states in the molecular lines, which is requisitely demanded for a charge-transport wire. PMID- 26282043 TI - Conductivity and Solvation Dynamics in Ionic Liquids. AB - It was shown recently that a simple dielectric continuum model predicts the integral solvation time of a dipolar solute ?tausolv? to be inversely proportional to the electrical conductivity sigma0 of an ionic solvent or solution. In this Letter, we provide a more general derivation of this connection and show that available data on coumarin 153 (C153) in ionic liquids generally support this prediction. The relationship between solvation time and conductivity can be expressed by ln(?tausolv?/ps) = 4.37 - 0.92 ln (sigma0/S m(-1)) in 34 common ionic liquids. PMID- 26282044 TI - Mechanism of Sequential Water Transportation by Water Loading and Release in Single-Walled Carbon Nanotubes. AB - Water in carbon nanotubes (CNTs) displays unique behaviors such as ring-like structure formation, anomalous hydrogen bonds, and fast transportation. We demonstrated the structures and stability of water in loading and release processes using a combination of X-ray diffraction analysis and hybrid reverse Monte Carlo simulations. Water formed nanoclusters in water loading, whereas layered structures were formed in water release. The water nanoclusters formed in water loading were well stabilized in CNTs. In contrast, in water release, the water layers were less stable than the water nanoclusters. The significant stabilization of nanoclusters in water loading and the relatively low stability of water layers in water release suggest easy water loading and release through CNTs, providing sequential water transportation through CNTs. PMID- 26282045 TI - Novel Ultrathin Membranes Composed of Organic Ions. AB - Until recently, construction of bilayers was an exclusive mission of nature. It requires careful choice of compounds, whose delicate interplay between head group attraction and chain repulsion engenders a truly unique balance over a narrow temperature range. We report the investigation of artificial bilayers composed of long-chained organic ions, such as dodecyltrimethylammonium (DMA(+)) and perfluorooctaonate (PFO(-)). Various ratios of DMA/PFO surfactants result in bilayers of different stability, thickness, area per molecule, and density profiles. In our quest for water filtration, we incorporated aquaporin protein into the DMA/PFO bilayer but did not observe sufficient stability of the system. We discuss further steps to utilize these surfactant bilayers as highly selective, salt-impermeable membranes. PMID- 26282046 TI - Gait variability and motor control in people with knee osteoarthritis. AB - Knee osteoarthritis (OA) is a common disease that impairs walking ability and function. We compared the temporal gait variability and motor control in people with knee OA with healthy controls. The purpose was to test the hypothesis that the temporal gait variability would reflect a more stereotypic pattern in people with knee OA compared with healthy age-matched subjects. To assess the gait variability the temporal structure of the ankle and knee joint kinematics was quantified by the largest Lyapunov exponent and the stride time fluctuations were quantified by sample entropy and detrended fluctuation analysis. The motor control was assessed by the soleus (SO) Hoffmann (H)-reflex modulation and muscle co-activation during walking. The results showed no statistically significant mean group differences in any of the gait variability measures or muscle co activation levels. The SO H-reflex amplitude was significantly higher in the knee OA group around heel strike when compared with the controls. The mean group difference in the H-reflex in the initial part of the stance phase (control-knee OA) was -6.6% Mmax (95% CI: -10.4 to -2.7, p=0.041). The present OA group reported relatively small impact of their disease. These results suggest that the OA group in general sustained a normal gait pattern with natural variability but with suggestions of facilitated SO H-reflex in the swing to stance phase transition. We speculate that the difference in SO H-reflex modulation reflects that the OA group increased the excitability of the soleus stretch reflex as a preparatory mechanism to avoid sudden collapse of the knee joint which is not uncommon in knee OA. PMID- 26282047 TI - Upper extremity coordination strategies depending on task demand during a basic daily activity. AB - Injury conditions affecting the upper extremity may lead to severe functional impairment and an accurate evaluation is needed in order to select the most effective treatment in a rehabilitation program. This study focused on simultaneous electromyographic and kinematic analysis to assess movement patterns of upper extremity during a basic daily activity, considering different demands existing within the task. Twenty-five healthy subjects, average age 19.8 ys SD 1.7 ys, with no upper extremity impairment, were assessed by means of electromyography (EMG) and a 3D motion capture system while performing a task that required reach, transport and release. Integrated EMG (iEMG), timing of muscle onset and active range of motion (AROM) were calculated for each subject. Data were compared within each phase and between the three phases and a repeated measure ANOVA was used for statistical analysis. We found early activation of upper trapezius associated with high activity of serratus anterior for proximal stability while anterior deltoid and triceps brachii performed shoulder flexion and elbow extension, in Reach phase. In Transport phase there was early and higher activation of upper trapezius, higher muscle activity of almost all muscles and increased AROM of all joints. No change in flexion/extension wrist posture with increased forearm muscles activity were identified as the main control strategy to keep optimal grasping. Triceps brachii was found to act as an important synergist in shoulder abduction and extension in free load conditions. Such information can lead clinicians to more specific assessment and subsequent better intervention in upper extremity rehabilitation. PMID- 26282048 TI - A Comment on 'Low Socioeconomic Status Is an Independent Risk Factor for Ischemic Stroke: A Case-Control Study in North Indian Population'. PMID- 26282049 TI - Congenital Short Bowel Syndrome: from clinical and genetic diagnosis to the molecular mechanisms involved in intestinal elongation. AB - Congenital Short Bowel Syndrome (CSBS) is a rare gastrointestinal disorder in which the mean length of the small intestine is substantially reduced when compared to its normal counterpart. Families with several affected members have been described and CSBS has been suggested to have a genetic basis. Recently, our group found mutations in CLMP as the cause of the recessive form of CSBS, and mutations in FLNA as the cause of the X-linked form of the disease. These findings have improved the quality of genetic counselling for CSBS patients and made prenatal diagnostics possible. Moreover, they provided a reliable starting point to further investigate the pathogenesis of CSBS, and to better understand the development of the small intestine. In this review, we present our current knowledge on CSBS and discuss hypotheses on how the recent genetic findings can help understand the cause of CSBS. PMID- 26282050 TI - Seat belt Morel-Lavallee seroma. PMID- 26282051 TI - Ipsilateral breast cancer recurrence after Deep Inferior Epigastric Perforator (DIEP) flap reconstruction: Incidence and radiological presentation. AB - PURPOSE: To assess the incidence and presentation of ipsilateral cancer recurrences (ICR) after deep inferior epigastric perforator (DIEP) flap reconstruction for breast cancer. PATIENTS AND METHODS: Data of 247 consecutive women with DIEP flap reconstruction after breast cancer in our institution between 1997 and 2009 were retrospectively reviewed. RESULTS: Mean follow-up time was 4.1years+/-3.2 (SD) (median: 3years; range: 1month - 14years). Thirty-one patients (12.5%, 95%CI: =8.7-17.3) presented 34 relapses, in average 4.1years+/ 2.6 after mastectomy: 14 (41%) were ipsilateral, 6 (18%) contralateral and 14 (41%) metastatic. ICRs occurred earlier (3.9 vs. 5.8years; P<0.05) than non-ICRs. Most ICRs (10/14, 71%) involved the periphery of the flap and presented as palpable nodules. The remaining (4/14, 29%) involved the axilla and 3/4 (75%) were palpable. Imaging procedures detected infra-clinical ICRs in 3 of 10 imaged patients (30%). CONCLUSION: ICRs after DIEP flap reconstruction are more frequent than contralateral recurrences suggesting the need for imaging follow-up of the reconstructed breast. PMID- 26282052 TI - Radiography of scoliosis: Comparative dose levels and image quality between a dynamic flat-panel detector and a slot-scanning device (EOS system). AB - PURPOSE: To compare radiation dose and image quality between a slot-scanning system (SSS) and a dynamic flat-panel detector (DFD) in assessing scoliosis in children. METHODS: An experimental study was first performed with a phantom to assess the quality of each device. The clinical part included a prospective observational dosimetric and qualitative comparative study with acquisition of whole-spine X-ray: SSS (31 children), DFD (26 children). Institutional review board approval and informed consent were obtained. Dosimetric statistical analysis was performed from dose area product (DAP) and entrance skin dose measured by thermo-luminescent dosimeters localized in the cervical, thoracic and sacral areas. Assessment of the diagnostic quality (phantom and clinical) was realized by independent evaluation by 3 observers, using statistical analysis of quality score and inter-observer reproducibility. RESULTS: DAP was equivalent with the 2 systems. Entrance skin dose was significantly higher with DFD in thoracic and pelvic regions (P<0.05). Image quality scores of the SSS were significantly better than DFD for a majority of criteria, in both phantom and clinical evaluations. CONCLUSION: For scoliosis evaluation, the SSS, compared to the DFD system, offers enhanced image quality while reducing the entrance skin dose in the most radiosensitive areas. PMID- 26282053 TI - Maize orthologs of rice GS5 and their trans-regulator are associated with kernel development. AB - Genome information from model species such as rice can assist in the cloning of genes in a complex genome, such as maize. Here, we identified a maize ortholog of rice GS5 that contributes to kernel development in maize. The genome-wide association analysis of the expression levels of ZmGS5, and 15 of its 26 paralogs, identified a trans-regulator on chromosome 7, which was a BAK1-like gene. This gene that we named as ZmBAK1-7 could regulate the expression of ZmGS5 and three of the paralogs. Candidate-gene association analyses revealed that these five genes were associated with maize kernel development-related traits. Linkage analyses also detected that ZmGS5 and ZmBAK1-7 co-localized with mapped QTLs. A transgenic analysis of ZmGS5 in Arabidopsis thaliana L. showed a significant increase in seed weight and cell number, suggesting that ZmGS5 may have a conserved function among different plant species that affects seed development. PMID- 26282054 TI - SCUBIDOO: A Large yet Screenable and Easily Searchable Database of Computationally Created Chemical Compounds Optimized toward High Likelihood of Synthetic Tractability. AB - De novo drug design is widely assisted by computational approaches that enable the generation of a tremendous amount of new virtual molecules within a short time frame. While the novelty of the computationally generated compounds can easily be assessed, such approaches often neglect the synthetic feasibility of the molecules, thus creating a potential hurdle that can be a barrier to further investigation. Therefore, we have developed SCUBIDOO, a freely accessible database concept that currently holds 21 million virtual products originating from a small library of building blocks and a collection of robust organic reactions. This large data set was reduced to three representative and computationally tractable samples denoted as S, M, and L, containing 9994, 99,977, and 999,794 products, respectively. These small sets are useful as starting points for ligand identification and optimization projects. The generated products come with synthesis instructions and alerts of possible side reactions, and we show that they exhibit drug-like properties while still extending into unexplored quadrants of chemical space, thus suggesting novelty. We show multiple examples that demonstrate how SCUBIDOO can facilitate the search around initial hits. This database might be a useful idea generator for early ligand discovery projects since it allows a focus on those molecules that are likely to be synthetically feasible and can therefore be studied further. Together with its modular building block construction principle, this database is also suitable for structure-activity relationship studies or fragment-growing strategies. PMID- 26282055 TI - Zingerone activates VMAT2 during MPP(+) -induced Cell Death. AB - Parkinson's disease (PD) is characterized by a progressive and selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and striatum. 1 Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is used to produce an animal model for PD, and it is converted to 1-methyl-4-phenylpyridine (MPP(+)) in animals. MPP(+) accumulation leads to neuronal cell death. Vesicular monoamine transporter 2 (VMAT2) regulates the accumulation of monoamine neurotransmitters into synaptic vesicles and is involved in neuroprotection against neurotoxin induced cell death. Recently, zingerone has been reported to reduce oxidative stress and inhibit inflammation. Therefore, we examined the effect of zingerone on neuronal cell death in a PD model. In an MPP(+) and MPTP-mediated PD model, neuronal cell survival was increased by zingerone without modifying neuroinflammation or reactive oxygen species generation. Zingerone also induced ERK activation and VMAT2 expression, leading to the attenuation of MPP(+)-induced neuronal cell death. Our current results suggest that zingerone has a neuroprotective effect in a PD model. PMID- 26282056 TI - Pulsed dye laser in treatment of steroid-induced atrophy. AB - BACKGROUND: One of the important and distressing cutaneous side effects of steroid therapy is skin atrophy, which has no definite and effective treatment. To the best of our knowledge, laser therapy for steroid-induced atrophic scars has not been investigated to date. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of pulsed dye laser in the treatment of steroid induced atrophic scars. METHODS: In this pilot study, 15 patients with at least one atrophic patch were treated with the 585-nm pulsed dye laser at 4-week interval sessions until achieving complete improvement or until patient were lost to follow-up. Clinical outcome was assessed via standard photographic method before each treatment session and after the final visit. An independent dermatologist evaluated the photographs. RESULT: All of the patients (13 females and two males) with 25-59 years of age experienced some degree of improvement, except one patient who withdrew from the treatment after three sessions. The treatment was well tolerated. CONCLUSION: The results of our study indicated that pulsed dye laser therapy could be employed as a new method in the treatment of steroid-induced atrophic scars. Pulsed dye laser might affect the lesions through inducing collagen deposition and production of more superficial dermal elastin as well as less unidirectional collagen in clusters. PMID- 26282057 TI - Use of transposase and ends of IS608 enables precise and scarless genome modification for modulating gene expression and metabolic engineering applications in Escherichia coli. AB - Various methods have been developed for gene disruption in bacteria; however, extra in vitro manipulation steps or the residual presence of a scar in the host chromosome limits the use of such methods. By utilizing the unique properties of ISHp608, we have developed a simple and precise method for genome manipulation in Escherichia coli that alters the gene sequence without leaving foreign DNA in the chromosome. This strategy involves PCR amplification of a DNA cassette containing ISHp608-LE (left end)-antibiotic resistance gene-counterselection marker-ISHp608 RE (right end) by using primers containing extensions homologous to the adjacent regions of the target gene on the chromosome. The lambda Red mediated recombination of the PCR product and antibiotic resistance screening results in transformants with a modified gene target. The ISHp608-LE-antibiotic resistance gene-counterselection marker-ISHp608-RE cassette can then be excised using a temperature sensitive plasmid expressing the TnpA transposase, which precisely cleaves ISHp608-LE and ISHp608-RE without leaving a scar sequence. We demonstrated lacZ gene point mutation repair, two precise disruptions of the lacZ gene and constructed a library of lacZ variants having variable beta galactosidase activity by changing its ribosome binding site sequences using the ISHp608 system. This technique can be used in E. coli genome modification and could be extended for use in other bacteria. PMID- 26282058 TI - Future goals of adolescents and young adults with chronic musculoskeletal pain. AB - BACKGROUND: Chronic non-specific musculoskeletal pain is a common problem among adolescents. This study investigates the importance of future goals and goal frustration for adolescents and young adults with chronic musculoskeletal pain compared to healthy adolescents. It also explores the impact that pain intensity, pain catastrophizing and depressive symptoms have on goal frustration for adolescents with chronic pain. METHODS: Using a cross-sectional design, we compared the importance and frustration of future goals for 42 adolescents and young adults with chronic musculoskeletal pain (41 women, 1 man) to those of 42 adolescents without pain (35 women, 7 men). For the adolescents with chronic pain, we also examined levels of pain intensity, pain catastrophizing and depressive symptoms to assess their ability to explain goal frustration levels. Statistics included t-tests, Mann-Whitney test and multivariate regression analysis. RESULTS: We found no differences in the importance of future goals, except for goals related to health, which were more important for adolescents with chronic pain (p = 0.03). Furthermore, adolescents with chronic pain perceived higher levels of goal frustration in all domains, except that related to school (p = 0.16). Depression explained goal frustration related to personal values (p = 0.02), social acceptance (p < 0.01), self-acceptance (p < 0.01) and health (p < 0.01). CONCLUSIONS: Dealing with chronic pain in adolescence and early adulthood does not seem to change future goals, but is associated with perceiving barriers to achieving them. The level of depressive symptoms seems to influence this relationship. Some caution is required in generalizing the results due to the relatively low number of male participants. PMID- 26282059 TI - Motor development in visually impaired children. PMID- 26282061 TI - Livelihoods, conflict and aid programming: is the evidence base good enough? AB - In conflict-affected situations, aid-funded livelihood interventions are often tasked with a dual imperative: to generate material welfare benefits and to contribute to peacebuilding outcomes. There may be some logic to such a transformative agenda, but does the reality square with the rhetoric? Through a review of the effectiveness of a range of livelihood promotion interventions- from job creation to microfinance--this paper finds that high quality empirical evidence is hard to come by in conflict-affected situations. Many evaluations appear to conflate outputs with impacts and numerous studies fail to include adequate information on their methodologies and datasets, making it difficult to appraise the reliability of their conclusions. Given the primary purpose of this literature--to provide policy guidance on effective ways to promote livelihoods- this silence is particularly concerning. As such, there is a strong case to be made for a restrained and nuanced handling of such interventions in conflict affected settings. PMID- 26282060 TI - MRSI via fully-refocused spatiotemporal encoding with polychromatic spectral pulses. AB - A novel method for the rapid acquisition of quality multi-slice 2D images targeting a small number of spectroscopic resonances, is introduced and illustrated. The method exploits the robustness derived from recently proposed spatiotemporal encoding (SPEN) methods, when operating in the so-called "fully refocused" mode. Fully-refocused SPEN provides high-fidelity single-shot images thanks to its refocusing of all offset-derived effects throughout the course of the acquisition. This refocusing, however, prevents exploiting such robustness for spectroscopic imaging. We propose here a solution to this limitation, based on the use of polychromatic refocusing pulses. It is shown that if used to address a series of a priori known resonance positions, these pulses can lead to quality spectroscopic images in a small number of scans - generally equal or slightly larger than the number of targeted peaks. Such strategy is explored in combination with both fully-refocused SPEN and echo-planar-imaging (EPI) acquisitions. The expected SPEN advantages were observed in both phantom-based models, and in in vivo results of fat and water separation in mice at 7 T. PMID- 26282062 TI - Phase III clinical study of maxacalcitol ointment in patients with palmoplantar pustulosis: A randomized, double-blind, placebo-controlled trial. AB - Palmoplantar pustulosis (PPP) often shows resistance to treatment. Vitamin D3 analog (VitD3 ) has been widely used for the treatment of psoriasis, however, the efficacy and safety of topical VitD3 treatment of PPP are not fully confirmed. Maxacalcitol topical ointment (22-oxacalcitriol [OCT]) was applied twice daily for 8 weeks. Evaluation of efficacy was based on scored skin findings for three main symptoms (erythema, pustules/vesicles and keratinization/scales). The primary and secondary end-points were the total and symptom-specific scores of skin findings, respectively. A total of 188 patients with moderate or severe PPP were enrolled in the study and were randomized into either the OCT group (n = 95) or placebo group (n = 93). The total scores (mean +/- standard error) of skin findings at the last observation adjusting for those on day 1 were 5.0 +/- 0.20 in the OCT group and 6.9 +/- 0.20 in the placebo group. There was a significant decrease in the total score of skin findings in the OCT group compared with the placebo group (P < 0.0001). In particular, the score of pustules/vesicles drastically decreased in the OCT group. In terms of safety, the incidence of adverse reactions in the OCT and placebo groups were 11.6% and 9.7%, respectively. These results indicate that OCT is effective and highly safe in the management of PPP. Topical OCT treatment was found to show a potent action on pustules/vesicles thereby contributing to the cure of PPP. PMID- 26282063 TI - Hybrid use of combined and sequential delivery of growth factors and ultrasound stimulation in porous multilayer composite scaffolds to promote both vascularization and bone formation in bone tissue engineering. AB - In this study, a multilayer coating technology would be adopted to prepare a porous composite scaffold and the growth factor release and ultrasound techniques were introduced into bone tissue engineering to finally solve the problems of vascularization and bone formation in the scaffold whilst the designed multilayer composite with gradient degradation characteristics in the space was used to match the new bone growth process better. The results of animal experiments showed that the use of low intensity pulsed ultrasound (LIPUS) combined with growth factors demonstrated excellent capabilities and advantages in both vascularization and new bone formation in bone tissue engineering. The degradation of the used scaffold materials could match new bone formation very well. The results also showed that only RGD-promoted cell adhesion was insufficient to satisfy the needs of new bone formation while growth factors and LIPUS stimulation were the key factors in new bone formation. PMID- 26282064 TI - Picking and nibbling in children and adolescents with eating disorders. AB - OBJECTIVE: Picking and nibbling (P&N), defined as eating in an unplanned and repetitious way between meals and snacks, is prevalent among adults with eating disorders (EDs), but unexamined among youth with EDs. This study sought to assess the prevalence of P&N in youth with EDs and its association with ED and comorbid pathology. METHOD: Youth (N = 515; ages 7-18) who presented to one outpatient ED research-clinical program were assessed for ED and comorbid pathology. RESULTS: Two-fifths (n = 214, 41.6%) of youth endorsed P&N. These individuals were older (p < .001) and had a higher percent expected body weight (p = .006) than those who denied P&N. Controlling for age and percent expected body weight, P&N was only associated with global ED pathology in youth with anorexia nervosa (AN) or atypical AN (p = .007). P&N was not associated with ED diagnosis, ED pathology in youth with bulimia nervosa or subclinical bulimia nervosa, binge eating, compensatory behaviors, secret eating, or the presence of a mood or anxiety disorder (p's > .05). DISCUSSION: Consistent with research in adults, P&N is prevalent but not significantly associated with ED pathology, except for global ED pathology in youth with AN/atypical AN, or comorbid disorders. PMID- 26282065 TI - Detection of Intraparenchymal Hemorrhage After Endovascular Therapy in Patients with Acute Ischemic Stroke Using Immediate Postprocedural Flat-Panel Computed Tomography Scan. AB - PURPOSE: To assess the diagnostic value of parenchymal hyperdense lesions visualized on the flat-panel CT scan in detecting/excluding intraparenchymal hemorrhage (IPH) after the endovascular treatment of acute stroke patients. METHODS: Two separate cohorts of acute ischemic stroke patients who underwent endovascular treatment were evaluated. In the first group, patients were evaluated for hyperdense parenchymal lesions immediately after the treatment with flat-panel CT scan; whereas, in the second group, patients underwent multidetector CT scan post procedure. IPH was defined as hyperdensity that persisted for >24 hours on follow up CT scan. RESULTS: A total of 30 patients were evaluated with flat panel, and 135 with multidetector CT scan immediately after the endovascular treatment. Hyperdense lesions were visualized on 7/30 (23%) of those evaluated with flat-panel CT versus 74/135 (55%) of those evaluated with multidetector CT scan. Based on 24-hour follow up imaging, hyperdense parenchymal lesions on immediate postprocedural flat-panel or multidetector CT studies had 100% sensitivity and negative predictive value for IPH; whereas, the specificity, and positive predictive value of such lesions were 88% and, 57% on the flat panel; and 53% and, 27% on the multidetector CT study, respectively. CONCLUSION: The absence of hyperdense lesions on immediate postprocedural flat-panel CT scan of ischemic stroke patients can exclude IPH with a high sensitivity and negative predictive value. The hyperdense parenchymal lesions visualized on flat-panel versus multidetector CT studies may have comparable sensitivity and negative predictive value for the detection of IPH. PMID- 26282067 TI - Experimental Demonstration of Underwater Acoustic Scattering Cancellation. AB - We explore an acoustic scattering cancellation shell for buoyant hollow cylinders submersed in a water background. A thin, low-shear, elastic coating is used to cancel the monopole scattering from an air-filled, neutrally buoyant steel shell for all frequencies where the wavelength is larger than the object diameter. By design, the uncoated shell also has an effective density close to the aqueous background, independently canceling its dipole scattering. Due to the significantly reduced monopole and dipole scattering, the compliant coating results in a hollow cylindrical inclusion that is simultaneously impedance and sound speed matched to the water background. We demonstrate the proposed cancellation method with a specific case, using an array of hollow steel cylinders coated with thin silicone rubber shells. These experimental results are matched to finite element modeling predictions, confirming the scattering reduction. Additional calculations explore the optimization of the silicone coating properties. Using this approach, it is found that scattering cross sections can be reduced by 20 dB for all wavelengths up to k0a = 0.85. PMID- 26282066 TI - The exercise-induced biochemical milieu enhances collagen content and tensile strength of engineered ligaments. AB - Exercise stimulates a dramatic change in the concentration of circulating hormones, such as growth hormone (GH), but the biological functions of this response are unclear. Pharmacological GH administration stimulates collagen synthesis; however, whether the post-exercise systemic milieu has a similar action is unknown. We aimed to determine whether the collagen content and tensile strength of tissue-engineered ligaments is enhanced by serum obtained post exercise. Primary cells from a human anterior cruciate ligament (ACL) were used to engineer ligament constructs in vitro. Blood obtained from 12 healthy young men 15 min after resistance exercise contained GH concentrations that were ~7 fold greater than resting serum (P < 0.001), whereas IGF-1 was not elevated at this time point (P = 0.21 vs. rest). Ligament constructs were treated for 7 days with medium supplemented with serum obtained at rest (RestTx) or 15 min post exercise (ExTx), before tensile testing and collagen content analysis. Compared with RestTx, ExTx enhanced collagen content (+19%; 181 +/- 33 vs. 215 +/- 40 MUg per construct P = 0.001) and ligament mechanical properties - maximal tensile load (+17%, P = 0.03 vs. RestTx) and ultimate tensile strength (+10%, P = 0.15 vs. RestTx). In a separate set of engineered ligaments, recombinant IGF-1, but not GH, enhanced collagen content and mechanics. Bioassays in 2D culture revealed that acute treatment with post-exercise serum activated mTORC1 and ERK1/2. In conclusion, the post-exercise biochemical milieu, but not recombinant GH, enhances collagen content and tensile strength of engineered ligaments, in association with mTORC1 and ERK1/2 activation. PMID- 26282068 TI - Health and economic burden of running-related injuries in runners training for an event: A prospective cohort study. AB - Prospective running-related injury (RRI) data from runners training for an event are scarce, especially with regard to RRI-associated costs. Therefore, the aim of this study was to investigate the prevalence and economic burden of RRIs in runners participating in an organized training program preparing them for an event. This was a prospective cohort study with 18 weeks of follow-up. Individuals aged 18 or older and registered to participate in an organized running program were eligible. Follow-up surveys were sent every 2 weeks to collect data about running exposure, RRIs, and costs. Of the 161 potential participants, 53 (32.9%) were included in this study. A total of 32 participants reported 41 RRIs. The mean prevalence during follow-up was 30.8% [95% confidence interval (CI) 25.6-36.0%]. Overuse was the main mechanism of RRI (85.4%, n = 35). An RRI was estimated to have an economic burden of ?57.97 (95% CI ?26.17-94.00) due to healthcare utilization (direct costs) and ?115.75 (95% CI ?10.37-253.73) due to absenteeism from paid work (indirect costs). These results indicate that the health and economic burden of RRIs may be considered significant for public health. Therefore, prevention programs are needed for runners participating in organized training programs. PMID- 26282069 TI - Thick corpus callosum in the second trimester can be transient and is of uncertain significance. AB - OBJECTIVES: Depiction of a thick corpus callosum (CC) in utero is rare, and is generally associated with severe brain anomalies. Our aim was to describe a group of fetuses diagnosed during second-trimester ultrasound examination as having an apparently isolated thick CC, which normalized subsequently in the cases followed to term. METHODS: Among 59 fetuses referred to the Ob-Gyn Ultrasound Division of Lis Maternity Hospital with suspected callosal anomalies between January 2013 and June 2014, we identified nine cases with an apparently isolated thick CC for inclusion in this retrospective cohort study. Length and body thickness of the CC were compared with previously published nomograms. Fetuses with a suspected isolated thick CC were identified and followed until delivery or termination of pregnancy (TOP). Evaluation consisted of chromosomal analysis, at least one magnetic resonance imaging (MRI) examination and repeat ultrasound examinations. Postnatal evaluation included brain ultrasound examination, MRI when indicated and neurodevelopmental assessment through validated pediatric questionnaires. RESULTS: The nine fetuses were diagnosed with an apparently isolated thick CC at a mean gestational age of 23 + 5 (range, 21-29) weeks. Eight exhibited a CC body thickness >= 2SD above the mean for gestational age and one exhibited only a thickened genu. Six also exhibited a relatively short CC. Two patients opted for TOP but declined autopsy. In five of the seven remaining fetuses, the CC thickness normalized during follow-up. In the remaining two, the increased CC thickness was a variant of the cingulate sulcus. The CC length remained <= 2SD in five of the six fetuses with a short CC. Fetal MRI was performed and confirmed the diagnosis in six fetuses. The karyotype was normal in all fetuses. Short-term neurodevelopmental outcome was reported as normal in all six children with complete follow-up. CONCLUSIONS: Although the number of fetuses in our study is relatively small, it seems that an apparently isolated thick CC is not necessarily associated with poor prognosis. In such cases, a definitive diagnosis should not be reached based on a single measurement and repeat follow-up examinations during the third trimester are recommended. Copyright (c) 2015 ISUOG. Published by John Wiley & Sons Ltd. PMID- 26282070 TI - Indigenous tropical spastic paraparesis in Madrid (Spain). Experience on screening of human T-lymphotropic virus. AB - We have recently documented a case of tropical spastic paraparesis by HTLV-I in a Spanish patient. HTLV-I infection is rare in Europe, and hardly ever is accompanied by symptoms, but if it does it could trigger a major health issue. This case is presented here, as well as a discussion on the situations in which HTLV-I detection is justified. An analysis was made of the HTLV diagnostic requests at our centre during 2014-2015 (n=123). The diagnostic algorithm was: 1) Enzyme immunoassay, 2) Reverse hybridization, and 3) Proviral DNA detection by PCR. The results showed several situations of HTLV screening, emphasising those related to paraparesis (22%). Seven cases of HTLV-I infection were found: five in patients from endemic regions, one in an HIV-infected patient, and the case of TSP mentioned above. HTLV-I surveillance in non-endemic regions is a challenging issue, as the cost-benefit ratio is not well-established. This case report emphasises the importance of including HTLV within the differential diagnosis of insidious spastic paraparesis. PMID- 26282072 TI - Is mitochondrial free radical theory of aging getting old? PMID- 26282071 TI - Home-based versus centre-based cardiac rehabilitation. AB - BACKGROUND: Cardiovascular disease is the most common cause of death globally. Traditionally, centre-based cardiac rehabilitation programmes are offered to individuals after cardiac events to aid recovery and prevent further cardiac illness. Home-based cardiac rehabilitation programmes have been introduced in an attempt to widen access and participation. This is an update of a review originally published in 2009. OBJECTIVES: To compare the effect of home-based and supervised centre-based cardiac rehabilitation on mortality and morbidity, health related quality of life, and modifiable cardiac risk factors in patients with heart disease. SEARCH METHODS: To update searches from the previous Cochrane review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 9, 2014), MEDLINE (Ovid, 1946 to October week 1 2014), EMBASE (Ovid, 1980 to 2014 week 41), PsycINFO (Ovid, 1806 to October week 2 2014), and CINAHL (EBSCO, to October 2014). We checked reference lists of included trials and recent systematic reviews. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared centre-based cardiac rehabilitation (e.g. hospital, gymnasium, sports centre) with home-based programmes in adults with myocardial infarction (MI), angina, heart failure or who had undergone revascularisation. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the eligibility of the identified trials and data were extracted by a single author and checked by a second. Authors were contacted where possible to obtain missing information. MAIN RESULTS: Seventeen trials included a total of 2172 participants undergoing cardiac rehabilitation following an acute MI or revascularisation, or with heart failure. This update included an additional five trials on 345 patients with heart failure. Authors of a number of included trials failed to give sufficient detail to assess their potential risk of bias, and details of generation and concealment of random allocation sequence were particularly poorly reported. In the main, no difference was seen between home- and centre-based cardiac rehabilitation in outcomes up to 12 months of follow up: mortality (relative risk (RR) = 0.79, 95% confidence interval (CI) 0.43 to 1.47, P = 0.46, fixed-effect), cardiac events (data not poolable), exercise capacity (standardised mean difference (SMD) = -0.10, 95% CI -0.29 to 0.08, P = 0.29, random-effects), modifiable risk factors (total cholesterol: mean difference (MD) = 0.07 mmol/L, 95% CI -0.24 to 0.11, P = 0.47, random-effects; low density lipoprotein cholesterol: MD = -0.06 mmol/L, 95% CI -0.27 to 0.15, P = 0.55, random-effects; systolic blood pressure: mean difference (MD) = 0.19 mmHg, 95% CI -3.37 to 3.75, P = 0.92, random-effects; proportion of smokers at follow up (RR = 0.98, 95% CI 0.79 to 1.21, P = 0.83, fixed-effect), or health-related quality of life (not poolable). Small outcome differences in favour of centre-based participants were seen in high density lipoprotein cholesterol (MD = -0.07 mmol/L, 95% CI -0.11 to 0.03, P = 0.001, fixed-effect), and triglycerides (MD = -0.18 mmol/L, 95% CI 0.34 to -0.02, P = 0.03, fixed-effect, diastolic blood pressure (MD = -1.86 mmHg; 95% CI -0.76 to -2.95, P = 0.0009, fixed-effect). In contrast, in home-based participants, there was evidence of a marginally higher levels of programme completion (RR = 1.04, 95% CI 1.01 to 1.07, P = 0.009, fixed-effect) and adherence to the programme (not poolable). No consistent difference was seen in healthcare costs between the two forms of cardiac rehabilitation. AUTHORS' CONCLUSIONS: This updated review supports the conclusions of the previous version of this review that home- and centre-based forms of cardiac rehabilitation seem to be equally effective for improving the clinical and health-related quality of life outcomes in low risk patients after MI or revascularisation, or with heart failure. This finding, together with the absence of evidence of important differences in healthcare costs between the two approaches, supports the continued expansion of evidence-based, home-based cardiac rehabilitation programmes. The choice of participating in a more traditional and supervised centre-based programme or a home-based programme should reflect the preference of the individual patient. Further data are needed to determine whether the effects of home- and centre-based cardiac rehabilitation reported in these short-term trials can be confirmed in the longer term. A number of studies failed to give sufficient detail to assess their risk of bias. PMID- 26282074 TI - Superior biofunctionality of dental implant fixtures uniformly coated with durable bioglass films by magnetron sputtering. AB - Bioactive glasses are currently considered the suitable candidates to stir the quest for a new generation of osseous implants with superior biological/functional performance. In congruence with this vision, this contribution aims to introduce a reliable technological recipe for coating fairly complex 3D-shaped implants (e.g. dental screws) with uniform and mechanical resistant bioactive glass films by the radio-frequency magnetron sputtering method. The mechanical reliability of the bioactive glass films applied to real Ti dental implant fixtures has been evaluated by a procedure comprised of "cold" implantation in pig mandibular bone from a dead animal, followed by immediate tension-free extraction tests. The effects of the complex mechanical strains occurring during implantation were analysed by scanning electron microscopy coupled with electron dispersive spectroscopy. Extensive biocompatibility assays (MTS, immunofluorescence, Western blot) revealed that the bioactive glass films stimulated strong cellular adhesion and proliferation of human dental pulp stem cells, without promoting their differentiation. The ability of the implant coatings to conserve a healthy stem cell pool is promising to further endorse the fabrication of new osseointegration implant designs with extended lifetime. PMID- 26282073 TI - Systemic modeling myeloma-osteoclast interactions under normoxic/hypoxic condition using a novel computational approach. AB - Interaction of myeloma cells with osteoclasts (OC) can enhance tumor cell expansion through activation of complex signaling transduction networks. Both cells reside in the bone marrow, a hypoxic niche. How OC-myeloma interaction in a hypoxic environment affects myeloma cell growth and their response to drug treatment is poorly understood. In this study, we i) cultured myeloma cells in the presence/absence of OCs under normoxia and hypoxia conditions and did protein profiling analysis using reverse phase protein array; ii) computationally developed an Integer Linear Programming approach to infer OC-mediated myeloma cell-specific signaling pathways under normoxic and hypoxic conditions. Our modeling analysis indicated that in the presence OCs, (1) cell growth-associated signaling pathways, PI3K/AKT and MEK/ERK, were activated and apoptotic regulatory proteins, BAX and BIM, down-regulated under normoxic condition; (2) beta1 Integrin/FAK signaling pathway was activated in myeloma cells under hypoxic condition. Simulation of drug treatment effects by perturbing the inferred cell specific pathways showed that targeting myeloma cells with the combination of PI3K and integrin inhibitors potentially (1) inhibited cell proliferation by reducing the expression/activation of NF-kappaB, S6, c-Myc, and c-Jun under normoxic condition; (2) blocked myeloma cell migration and invasion by reducing the expression of FAK and PKC under hypoxic condition. PMID- 26282075 TI - A stochastic model for soft tissue failure using acoustic emission data. AB - The strength of soft tissues is due mainly to collagen fibers. In most collagenous tissues, the arrangement of the fibers is random, but has preferred directions. The random arrangement makes it difficult to make deterministic predictions about the starting process of fiber breaking under tension. When subjected to tensile stress the fibers are progressively straighten out and then start to be stretched. At the beginning of fiber breaking, some of the fibers reach their maximum tensile strength and break down while some others remain unstressed (this latter fibers will assume then bigger stress until they eventually arrive to their failure point). In this study, a sample of human esophagi was subjected to a tensile breaking of fibers, up to the complete failure of the specimen. An experimental setup using Acoustic Emission to detect the elastic energy released is used during the test to detect the location of the emissions and the number of micro-failures per time unit. The data were statistically analyzed in order to be compared to a stochastic model which relates the level of stress in the tissue and the probability of breaking given the number of previously broken fibers (i.e. the deterioration in the tissue). The probability of a fiber breaking as the stretch increases in the tissue can be represented by a non-homogeneous Markov process which is the basis of the stochastic model proposed. This paper shows that a two-parameter model can account for the fiber breaking and the expected distribution for ultimate stress is a Frechet distribution. PMID- 26282076 TI - Synthesis of fluorinated dimethacrylate monomer and its application in preparing Bis-GMA free dental resin. AB - With the aim to reduce human exposure to Bis-phenol A derivatives, a novel fluorinated dimethacrylate monomer FUDMA was synthesized and mixed with triethyleneglycol dimethacrylate (TEGDMA) to prepare 2,2-bis[4-(2-hydroxy-3 methacryloy- loxypropyl)phenyl]propane (Bis-GMA) free dental resin system. Physicochemical properties, such as double bond conversion (DC), polymerization shrinkage (VS), water sorption (WS) and solubility (SL), flexural strength (FS) and modulus (FM), and fracture energy of FUDMA/TEGDMA resin system were investigated. Bis-GMA/TEGDMA resin system was used as a control. The results showed that, compared with Bis-GMA/TEGDMA resin system, FUDMA/TEGDMA had advantages like higher DC, lower VS, and higher fracture energy, but had no disadvantages. Therefore, FUDMA/TEGDMA resin system had better comprehensive physicochemical properties than Bis-GMA/TEGDMA resin system, and FUDMA had potential to be used as a substitute for Bis-GMA. PMID- 26282077 TI - Compressive fatigue and fracture toughness behavior of injectable, settable bone cements. AB - Bone grafts used to repair weight-bearing tibial plateau fractures often experience cyclic loading, and there is a need for bone graft substitutes that prevent failure of fixation and subsequent morbidity. However, the specific mechanical properties required for resorbable grafts to optimize structural compatibility with native bone have yet to be established. While quasi-static tests are utilized to assess weight-bearing ability, compressive strength alone is a poor indicator of in vivo performance. In the present study, we investigated the effects of interfacial bonding on material properties under conditions that re-capitulate the cyclic loading associated with weight-bearing fractures. Dynamic compressive fatigue properties of polyurethane (PUR) composites made with either unmodified (U-) or polycaprolactone surface-modified (PCL-) 45S5 bioactive glass (BG) particles were compared to a commercially available calcium sulfate and phosphate-based (CaS/P) bone cement at physiologically relevant stresses (5 30 MPa). Fatigue resistance of PCL-BG/polymer composite was superior to that of the U-BG/polymer composite and the CaS/P cement at higher stress levels for each of the fatigue failure criteria, related to modulus, creep, and maximum displacement, and was comparable to human trabecular bone. Steady state creep and damage accumulation occurred during the fatigue life of the PCL-BG/polymer and CaS/P cement, whereas creep of U-BG/polymer primarily occurred at a low number of loading cycles. From crack propagation testing, fracture toughness or resistance to crack growth was significantly higher for the PCL-BG composite than for the other materials. Finally, the fatigue and fracture toughness properties were intermediate between those of trabecular and cortical bone. These findings highlight the potential of PCL-BG/polyurethane composites as weight-bearing bone grafts. PMID- 26282078 TI - Effects of aging procedures on the molecular, biochemical, morphological, and mechanical properties of vacuum-formed retainers. AB - The influence of intraoral exposure procedures on the physical characteristics of thermoplastic vacuum-formed retainers (VFRs) is still unclear. The effects of thermoforming and intraoral use on the molecular, chemical, morphological, and mechanical properties of thermoplastic VFRs were investigated. VFRs with a 0.8-mm thick thermoplastic PETG sheet acquired from 48 patients were investigated with two aging procedures, including vacuum forming and intraoral exposure, for 2-week and 6-month. Eight evaluating sites for thermoplastic VFRs were assessed with seven analytical techniques. LM, SEM, and AFM microscopic findings showed that the surface characteristics increased with increasing in vivo exposure time (a four-fold increase) and varied depending on the sites evaluated (an occlusal surface). Raman and EDX spectroscopic findings showed that aging procedures led to a significant change in the molecular composition of VFRs, leading to a decrease in the composition rate of carbon (C) and the presence of silicon (Si), phosphorus (P), and calcium (Ca). Compressive strength and tensile tests showed that aging procedures led to a significant increase (P<0.01) in ultimate tensile strength, elastic modulus, the stored energy at a 6-mm deflection (u6 mm), and the compressed load at a 3-mm deflection (sigma3 mm). Thermoforming led to a smoother surface and no crystallization of PETG sheets. Intraoral exposure accelerated changes in surface morphology, tensile strength, and elastic modulus of VFRs. This change was site-specific and enhanced with an increase in intraoral exposure time. Therefore, thermoforming and in vivo oral exposure procedures led to the molecular, morphological, and mechanical properties of thermoplastic VFRs. PMID- 26282079 TI - Neural changes associated with semantic processing in healthy aging despite intact behavioral performance. AB - Semantic memory recruits an extensive neural network including the left inferior prefrontal cortex (IPC) and the left temporoparietal region, which are involved in semantic control processes, as well as the anterior temporal lobe region (ATL) which is considered to be involved in processing semantic information at a central level. However, little is known about the underlying neuronal integrity of the semantic network in normal aging. Young and older healthy adults carried out a semantic judgment task while their cortical activity was recorded using magnetoencephalography (MEG). Despite equivalent behavioral performance, young adults activated the left IPC to a greater extent than older adults, while the latter group recruited the temporoparietal region bilaterally and the left ATL to a greater extent than younger adults. Results indicate that significant neuronal changes occur in normal aging, mainly in regions underlying semantic control processes, despite an apparent stability in performance at the behavioral level. PMID- 26282080 TI - Biosimilars in rheumatology: current perspectives and lessons learnt. AB - Biosimilars, based on biopharmaceuticals approved by regulatory agencies that are no longer under patent protection, have efficacy and safety comparable to their reference products, and are a new therapeutic option to treat inflammatory diseases. Biosimilars must be distinguished from 'biomimics' or 'biocopies', which are marketed in some countries but have not been evaluated according to the stringent regulatory pathway used for biosimilars. CT-P13, based on infliximab, was the first biosimilar approved for the treatment of inflammatory diseases; however, some countries did not allow extrapolation of indications to all eight diseases for which the reference drug infliximab is approved. Antidrug antibodies can reduce drug levels and affect clinical efficacy, but although available data suggest that biosimilars and their reference products have comparable immunogenicity, this important property might differ between individual biopharmaceuticals. This Review discusses biosimilars already approved within the past 3 years to treat rheumatic diseases, as well as others that are currently under development. The main challenges posed by biosimilars are also addressed, such as the extrapolation of indications to diseases only studied for the reference drug, and the definition of strategies for adequate pharmacovigilance to monitor biosimilars after marketing approval. PMID- 26282081 TI - Autoinflammation. Management of hereditary recurrent fevers--SHARE experience. AB - Although new therapeutic options are available for patients with autoinflammatory diseases, evidence-based treatment guidelines are lacking. An initiative in European paediatric rheumatology aims to develop best-practice recommendations for the management of these rare disorders. PMID- 26282083 TI - Connective tissue diseases. Skin gene expression profiles in SSc. PMID- 26282082 TI - Cardiovascular comorbidity in rheumatic diseases. AB - Patients with rheumatoid arthritis (RA) and other inflammatory joint diseases (IJDs) have an increased risk of premature death compared with the general population, mainly because of the risk of cardiovascular disease, which is similar in patients with RA and in those with diabetes mellitus. Pathogenic mechanisms and clinical expression of cardiovascular comorbidities vary greatly between different rheumatic diseases, but atherosclerosis seems to be associated with all IJDs. Traditional risk factors such as age, gender, dyslipidaemia, hypertension, smoking, obesity and diabetes mellitus, together with inflammation, are the main contributors to the increased cardiovascular risk in patients with IJDs. Although cardiovascular risk assessment should be part of routine care in such patients, no disease-specific models are currently available for this purpose. The main pillars of cardiovascular risk reduction are pharmacological and nonpharmacological management of cardiovascular risk factors, as well as tight control of disease activity. PMID- 26282084 TI - Clinical characteristics associated with BRAF, NRAS and KIT mutations in Japanese melanoma patients. AB - BACKGROUND: The importance of the genetic background of melanoma cells to the individual susceptibility to treatment has become apparent. In Caucasians, BRAF mutations are frequently detected in lesions on the skin of younger patients compared to NRAS and KIT mutations. However, clinical and pathological characteristics associated with BRAF, NRAS and KIT mutations have not been fully evaluated in East Asians. OBJECTIVE: To clarify clinical and pathological characteristics associated with BRAF, NRAS and KIT mutations in Japanese melanoma patients. METHODS: Clinical data were retrospectively collected from 11 hospitals in Japan. BRAF, NRAS and KIT mutations were evaluated with polymerase chain reaction and Sanger sequencing. The relationships between these gene mutations and pathological and clinical findings were analyzed. RESULTS: The number of cases examined was 171 (primary: 135, metastases: 11, paired: 25), and all were Japanese patients. The detection rates of BRAF, NRAS and KIT mutations were 30.4%, 12.3% and 12.9%, respectively. Compared with the wild type, the presence of BRAF mutations was significantly associated with younger age (median, 50.0 years vs. 70.0 years, p<0.001). BRAF mutation was frequently detected in the lesions of the scalp (80%; 4/5), trunk (72.0%; 18/25), extremities (56.7%; 17/30) and neck (44.4%; 4/9), and the least prevalent were the face (22.2%; 2/9), nail (12.5%; 3/24), palm or sole (8.9%; 4/45) and mucosa (0%). NRAS mutations were prevalent in the face (33.3%) and palm or sole (20.0%), and the median age of these patients was 70.5 years. A KIT mutation was observed in the nail apparatus (25%), palm or sole (15.6%) and mucosa (18.2%). The median age of the patients with a KIT mutation was 63.0 years. Heterogeneity of mutations between primary and metastatic lesions was detected in six of 25 cases (24%). Solar elastosis was identified in 12 of 71 cases (15.3%), among which four cases harbored BRAF(V600E) (2 cases), BRAF(V600K), NRAS(Q61K) or NRAS(Q61L), respectively. CONCLUSION: Some clinical characteristics associated with BRAF, NRAS and KIT mutations were observed in Japanese patients, and we observed both similarities to and differences from those of Caucasians. Our findings could provide useful information in efforts to clarify the tumor genesis of malignant melanomas. PMID- 26282085 TI - Effects of rhododendrol and its metabolic products on melanocytic cell growth. AB - BACKGROUND: Rhododendrol (RD), a skin-whitening agent, is believed to be associated with cases of cosmetics-related leukoderma that have been reported in Japan. Recently, we have shown that RD is catalyzed by tyrosinase to produce putative toxic metabolites RD-catechol and RD-cyclic catechol. OBJECTIVE: To examine the cytotoxicity and production of reactive oxygen species (ROS) in melanocytic cells by RD and its metabolic products. METHODS: The growth inhibitory effect of RD or its metabolite on the normal human epidermal melanocyte (NHEM) and B16F1 cells was assessed by cell counting or WST assay. ROS production was detected by flow cytometry and confocal microscopy after cells were treated with 2',7'-dichlorofluorescein and RD or its metabolite. RESULTS: Growth of NHEM derived from African American (NHEMb) and B16F1 cells was suppressed by 300MUM or more RD. Growth inhibitory activity of RD (IC50 of B16F1: 671MUM) was weaker than hydroquinone (IC50 of B16F1: 28.3MUM) or resveratrol (IC50 of B16F1: 27.1MUM). Flow cytometric analysis detected ROS production in the NHEMb and B16F1 cells exposed to RD. However, neither RD nor H2O2 increased the subG1 fraction of these melanocytic cells. RD-catechol and RD-cyclic catechol inhibited growth of NHEMb and B16F1 cells much more strongly than did RD. RD catechol, as well as RD, produced ROS detected by both flow cytometry and immunostaining, while RD-cyclic catechol produced a hardly detectable amount of ROS in B16F1 cells. CONCLUSIONS: These results suggest that RD exerts the cytotoxicity in melanocytic cells through its oxidative metabolites and that ROS plays a role in RD-mediated cytotoxicity. PMID- 26282086 TI - Removal of atrazine in water by combination of activated carbon and dielectric barrier discharge. AB - Efficiency of modern wastewater treatment plants to remove or decompose persistent contaminants in low concentration is often insufficient to meet the demands imposed by governmental laws. Novel, efficient and cheap methods are required to address this global issue. We developed a new type of plasma reactor, in which atrazine decomposition by atmospheric dielectric barrier discharge (DBD) in dry air is combined with micropollutant adsorption on activated carbon textile and with extra bubbling of generated ozone. Investigation of reaction kinetics and by-product analysis shows that increasing input power with a factor 3.5 leads to deeper atrazine oxidation without significantly changing energy yield of atrazine removal. By-products of first and later generations are detected with HPLC-MS analysis in water and adsorbed on the activated carbon textile. Our reactor is compared in energy efficiency with reactors described in literature, showing that combination of plasma discharge with pollutant adsorption and ozone recycling is attractive for future applications of water treatment. PMID- 26282087 TI - Selective adsorption of silver(I) ions over copper(II) ions on a sulfoethyl derivative of chitosan. AB - This study presents a simple and effective method of preparation of N-(2 sulfoethyl) chitosan (NSE-chitosan) that allows obtaining a product with a degree of modification up to 1.0. The chemical structure of the obtained polymers was confirmed by FT-IR and 1H NMR spectroscopies. Cross-linking of N-(2-sulfoethyl) chitosans by glutaraldehyde allows preparation of sorbents for removal and concentration of metal ions. Capacity of sorbents towards hydroxide ions was determined depending on the degree of sulfoethylation under static and dynamic conditions. Dissociation constants of functional amino groups of the analyzed sorbents were determined by potentiometric titration. It was shown that basicity of the amino groups decreased (wherein pKa decreased from 6.53 to 5.67) with increase in degree of sulfoethylation. It explains the significant influence of sulfo groups on selectivity of sorption of metal ions on N-(2-sulfoethyl) chitosan-based sorbents. The investigated substances selectively remove copper(II) and silver(I) ions from solutions of complex composition. Wherein the selectivity coefficient KAg/Cu increased to 20 (pH 6.5, ammonium acetate buffer solution) with increase in degree of sulfoethylation of the sorbent up to 1.0. PMID- 26282088 TI - Utilization of the dilute acidic sulfate effluent as resources by coupling solvent extraction-oxidation-hydrolysis. AB - The pollution risk of dilute acidic sulfate effluent (DASE),which is discharged from titanium dioxide factories heavily every year, has sparked the recycling of sulfuric acid, iron and water. In this study, a new green recovery process for the DASE is proposed based on coupling solventextraction-oxidation-hydrolysis. Compared to the conventional ways, this innovative method allows the effective extraction of sulfuric acid and the precipitation of FexOy.nH2O in onestep without adding inorganic neutralizer or precipitant. Trioctylamine (TOA) in kerosene (20-50%) was used as an organic phase for solvent extraction. The hydrolytic productions and the raffinate purified by a cation exchange were evaluated using XRD and ICP-OES, respectively. The initial pH of 0.63 and Fe(II) concentration of 0.1 mol/L in the DASE, the volume ratio of organic toaqueous phase (O/A) of 3/1, and reaction temperature of 25 degrees C were determined as the optimal conditions. Under this conditions, Fe(II) was transformed as yellow precipitation which was characterized as alpha-FeOOH, and pH of raffinate was in the range of 3.6-3.8. PMID- 26282089 TI - Immunization Equity. AB - Health inequities are the unjust differences in health among different social groups. Unfortunately, inequities are the norm, both in terms of health status and access to, and use of, health services. Childhood immunizations reduce the incidence of vaccine-preventable diseases and represent a cost-effective way to foster health equity. This paper reflects a 2015 review of data from surveys conducted in developing countries from 2005 to 2011 that show significant inequities in immunization coverage and discusses several initiatives currently underway (including Gavi, the Vaccine Alliance) that are directed at increasing childhood immunizations or reducing or abolishing overall health inequities. These initiatives have already had a significant impact on disease burden and childhood mortality and give rise to optimism that health disparities may further be reduced and health equity achieved as a result of investments made in immunization. PMID- 26282090 TI - Impairment of the accumulation of decidual T cells, NK cells, and monocytes, and the poor vascular remodeling of spiral arteries, were observed in oocyte donation cases, regardless of the presence or absence of preeclampsia. AB - In oocyte donation (OD) pregnancies, a fetus is a complete allograft to the maternal host and OD pregnancies are an independent risk factor for preeclampsia. Immunocompetent cells contribute to spiral artery remodeling and the failure of this process could contribute to the pathophysiology of preeclampsia. Recent data have shown that impaired autophagy of extravillous trophoblasts (EVT) may induce poor vascular remodeling in preeclampsia. We have studied the distribution of T cells, NK cells and macrophages in the decidua basalis of 14 normotensive OD pregnancies, 5 preeclamptic OD cases, 16 normotensive pregnancy cases, and 13 preeclamptic cases in natural pregnancy or autologous oocyte IVF-ET (NP/IVF). The populations of decidual CD3(+)T cells, CD8(+)T cells, CD4(+)T cells, Foxp3(+)Treg cells, CD56(+)NK cells, and CD68(+) macrophages in preeclampsia were significantly smaller than those in normal pregnancy in NP/IVF. Those frequencies in normotensive OD pregnancies or preeclamptic cases in OD pregnancies were similar to those in preeclamptic cases in NP/IVF. Impaired vascular remodeling was observed in OD pregnancies, regardless of the presence or absence of preeclampsia. The expression of p62, an impaired autophagy marker in EVT of normotensive or preeclamptic OD pregnancies, was significantly higher than that in normal pregnancies in NP/IVF. Immunological change in the decidua basalis and impairment of autophagy in EVT may induce impairment of spiral artery remodeling in OD pregnancies. PMID- 26282091 TI - Is pretreatment cystometry important in predicting response to mirabegron in women with overactive bladder symptoms? AB - INTRODUCTION AND HYPOTHESIS: The aim of this study was to evaluate for any association between pretreatment cystometry results and outcome of treatment with mirabegron in women with overactive bladder (OAB) symptoms. METHODS: This was a prospective observational study of women with OAB symptoms that proved refractory to conservative management. All women underwent filling and voiding subtraction cystometry prior to further treatment. Women were treated with mirabegron 50 mg once daily, and outcomes were evaluated after 6 weeks' treatment. The primary outcome measure was change in symptoms as indicated by response to the Patient Global Impression of Improvement (PGI-I) scale. The presence of detrusor overactivity (DO), the highest detrusor pressure recorded during the filling phase, the presence of urodynamic stress incontinence (USI), cystometric capacity, voided volume, maximum flow rate and detrusor pressure at maximum flow were all compared between responders and nonresponders. RESULTS: The study population consisted of 169 women; response rate to mirabegron was 69.8 %. There was no association between the presence of DO or maximum detrusor pressure during filling and USI, cystometric capacity, maximum flow rate and detrusor pressure at maximum flow and treatment response. In a subgroup with OAB symptoms refractory to previous treatment with antimuscarinics, there was an association between the presence of DO and a positive treatment response (p = 0.02). CONCLUSIONS: Overall, there is no association between urodynamic findings and response to treatment with mirabegron. This may reflect the fact that mirabegron's mode of action mechanisms are not measurable using cystometry. In women with refractory symptoms, however, the presence of DO is associated with a positive response to treatment. PMID- 26282092 TI - Management of arterial and venous hemorrhage during sacrospinous ligament fixation: cases and review of the literature. AB - INTRODUCTION AND HYPOTHESIS: Sacrospinous ligament fixation (SSLF) for pelvic organ prolapse repair can incur significant intraoperative hemorrhage. Management of vascular injury is challenging because of limited visualization of the surrounding pararectal space and is not well described in the literature. METHODS: We evaluate cases of intraoperative venous and arterial hemorrhage during SSLF. Based on a review of the literature, we present a systematic approach to the treatment of venous and arterial hemorrhage associated with SSLF. RESULTS: Vascular injury to the hypogastric and pudendal venous plexi may be controlled using directed compression and topical hemostatic agents. Vascular injury to the inferior gluteal artery, its coccygeal branch, or other arteries, may require embolization. CONCLUSION: Life-threatening bleeding is a rare complication of transvaginal SSLF. Knowledge of surrounding pelvic vascular anatomy, treatment options, and communication with ancillary staff is essential for the treatment of sacrospinous ligament hemorrhage. PMID- 26282093 TI - Abdominal sacral colpopexy versus sacrospinous ligament fixation: a cost effectiveness analysis. AB - INTRODUCTION AND HYPOTHESIS: For the surgical correction of apical prolapse the abdominal approach is associated with better outcomes; however, it is more expensive than the transvaginal approach. This cost-effectiveness analysis compares abdominal sacral colpopexy (ASC) with sacrospinous ligament fixation (SSLF) to determine if the improved outcomes of ASC justify the increased expense. METHODS: A decision-analytic model was created comparing ASC with SSLF using data-modeling software, TreeAge Pro (2013), which included the following outcomes: post-operative stress urinary incontinence (SUI) with possible mid urethral sling (MUS) placement, prolapse recurrence with possible re-operation, and post-operative dyspareunia. Cost-effectiveness was defined as an incremental cost-effectiveness ratio (ICER) of less than $50,000 per quality-associated life year (QALY). Base-case, threshold, and one-way sensitivity analyses were performed. RESULTS: At the baseline, ASC is more expensive than SSLF ($13,988 vs $11,950), but is more effective (QALY 1.53 vs 1.45) and is cost-effective (ICER $24,574/QALY) at 2 years. ASC was not cost-effective if the following four thresholds were met: the rate of post-operative SUI was above 36 % after ASC or below 28 % after SSLF; the rate of MUS placement for post-operative SUI was above 60 % after ASC or below 13 % after SSLF; the rate of recurrent prolapse was above 15 % after ASC or below 4 % after SSLF; the rate of post-operative dyspareunia was above 59 % after ASC or below 19 % after SSLF. CONCLUSIONS: Abdominal sacral colpopexy can be cost-effective compared with sacrospinous ligament fixation; however, as the post-operative outcomes of SSLF improve, SSLF can be considered a cost-effective alternative. PMID- 26282094 TI - Impact of pelvic floor muscle training in the postpartum period. AB - INTRODUCTION AND HYPOTHESIS: Our study piloted a novel, two-tiered approach to delivering pelvic floor muscle training (PFMT) to postpartum women involving a standardized group workshop followed by the opportunity to self-select for individual PFMT sessions. The aim of the study was to evaluate the outcomes in women who self-selected for individual PFMT using validated quality of life (QoL) questionnaires, the Pelvic Floor Distress Inventory-20 (PFDI-20), the Pelvic Floor Impact Questionnaire-7 (PFIQ-7), the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12 (PISQ-12), as well as the Modified Oxford Scale (MOS) for strength. Women's satisfaction with the program was also assessed. METHODS: This was a single-center prospective cohort study conducted between December 2013 and September 2014. Changes from baseline to postintervention QoL and MOS scores were tested using the Wilcoxon signed-rank test. RESULTS: Two hundred and eighteen women attended the workshop, 54 enrolled in PFMT sessions, and 50 completed follow-up. Significant improvements were seen in the PFDI-20 (mean change -41.8, p < 0.001) and PFIQ-7 (mean change -23.0, p < 0.001) questionnaires. Results for the PISQ-12 could not be tabulated, as there were too many missing responses. The MOS score was significantly improved from baseline (4; range {0-5} compared with 3; range {0-4}; p < 0.001). Forty-nine of 50 women's expectations for the program were met [9 of 10; standard deviation (SD) 1.4]. CONCLUSION: Results suggest that a two-tiered, self-selection approach to administering PFMT in the postpartum period contributes to significant improvements in pelvic floor function, QoL, MOS strength, and to high satisfaction rates. PMID- 26282095 TI - Quantification of vehicle mixture effects on in vitro transdermal chemical flux using a random process diffusion model. AB - The effect of vehicle mixtures on transdermal permeation has been studied using transient flux profiles from porcine skin flow through diffusion cells. Such data characteristically exhibit a large amount of variability between treatments (vehicle and penetrant combinations) as well as noise within treatments. A novel mathematical model has been used that describes longitudinal variation as a time varying diffusivity. Between treatment variability was described by a mixed effects model. A quantitative structure property relationship (QSPR) was developed to describe the effects of the penetrant and vehicle mixture properties on the mean diffusivity and partition coefficient in the membrane. The relationship included terms for the logP and molecular weight of the penetrant and the refractive index of the vehicle mixture with R(2)>0.95 for K and >0.9 for partition coefficient (as K?D). This analysis improved on previous work, finding a more parsimonious model with higher predictability, while still identifying the mixture refractive index as a key descriptor in predicting vehicle effects. The concordance with established and expected relationships lends confidence to this new methodology for evaluating transient, finite dose, transdermal flux data collected using traditional experimental methods. PMID- 26282096 TI - Enzyme sensitive, surface engineered nanoparticles for enhanced delivery of camptothecin. AB - To achieve a drug delivery system combining the programmable long circulation and targeting ability, surface engineering nanoparticles (NPs), having a sandwich structure consisting of a long circulating outmost layer, a targeting middle layer and a hydrophobic innermost core were constructed by mixing a matrix metalloproteinase MMP2 and MMP9-sensitive copolymers (mPEG-Pep-PCL) and folate receptor targeted copolymers (FA-PEG-PCL). Their physiochemical traits including morphology, particle size, drug loading content, and in vitro release profiles were studied. In vitro studies validated that the inhibition efficiency of tumor cells was effectively correlated with NP concentrations. Furthermore, The PEG layer would detach from the NPs due to the up-regulated extracellular MMP2 and MMP9 in tumors, resulting in the exposure of folate to enhance the cellular internalization via folate receptor mediated endocytosis, which accelerated the release rate of CPT in vivo. The antitumor efficacy, tumor targeting ability and bio-distribution of the NPs were examined in a B16 melanoma cells xenograft mouse model. These NPs showed improved tumor target ability and enhanced aggregation of camptothecin (CPT) in tumor site and prominent suppression of tumor growth. Thus this mPEG-Pep-PCL@FA-PEG-PCL core-shell structure NP could be a better candidate for the tumor specific delivery of hydrophobic drug. PMID- 26282097 TI - Liposomes loaded with a STING pathway ligand, cyclic di-GMP, enhance cancer immunotherapy against metastatic melanoma. AB - Malignant melanomas escape immunosurveillance via the loss/down-regulation of MHC I expression. Natural killer (NK) cells have the potential to function as essential effector cells for eliminating melanomas. Cyclic di-GMP (c-di-GMP), a ligand of the stimulator of interferon genes (STING) signal pathway, can be thought of as a new class of adjuvant against cancer. However, it is yet to be tested, because technologies for delivering c-di-GMP to the cytosol are required. Herein, we report that c-di-GMP efficiently activates NK cells and induces antitumor effects against malignant melanomas when loaded in YSK05 lipid containing liposomes, by assisting in the efficient delivery of c-di-GMP to the cytosol. The intravenous administration of c-di-GMP encapsulated within YSK05 liposomes (c-di-GMP/YSK05-Lip) into mice efficiently induced the production of type I interferon (IFN) as well as the activation of NK cells, resulting in a significant antitumor effect in a lung metastasis mouse model using B16-F10. This antitumor effect was dominated by NK cells. The infiltration of NK cells was observed in the lungs with B16-F10 melanomas. These findings indicate that the c di-GMP/YSK05-Lip induces MHC-I non-restricted antitumor immunity mediated by NK cells. Consequently, c-di-GMP/YSK05-Lip represents a potentially new adjuvant system for use in immunotherapy against malignant melanomas. PMID- 26282098 TI - Notch1 targeting siRNA delivery nanoparticles for rheumatoid arthritis therapy. AB - Notch pathway plays a pivotal role in synoviocytes involved in progression of rheumatoid arthritis (RA). Herein, we designed the Notch1 targeting siRNA delivery nanoparticles (siRNA-NPs) in order to confirm the anti-inflammatory effect in collagen-induced arthritis (CIA) model. The siRNA-NPs were successfully produced by encapsulating polymerized siRNA (poly-siRNA) into thiolated glycol chitosan (tGC) nanoparticles in aqueous condition. The in vitro Notch1 inhibition of siRNA-NPs in murine macrophage cell (RAW 264.7) was confirmed using confocal microscopy and real time PCR. Fluorescently labeled siRNA-NPs were successfully transfected in RAW 264.7 and modulated the expression of Notch1 in mRNA level. For in vivo study, siRNA-NPs exhibited the higher targeting efficiency in the arthritic joins of CIA mice, confirmed by the near-infrared fluorescence (NIRF) imaging. Furthermore, inhibition of Notch1 with siRNA-NPs resulted in retarded progression of inflammation, bone erosion, and cartilage damage in CIA mice. Novel Notch1 targeting siRNA delivery system of siRNA-NPs showed effective RA treatment by suppressing Notch1 signaling pathway without undesirable severe toxicity. Thus, Notch1 inhibiting siRNA-NPs demonstrated the great potential in RA therapeutics that was hard to be achieved using conventional drugs. PMID- 26282099 TI - Efficacy and safety of the first and repeated intradetrusor injections of abobotulinum toxin A 750 U for treating neurological detrusor overactivity. AB - PURPOSE: To assess clinical and urodynamic efficacy of the first and repeated intradetrusor injections of abobotulinum toxin A (Dysport((r)), Ipsen((r)), France) in patients with neurogenic detrusor overactivity (NDO) refractory to anticholinergic treatment. METHODS: A single-center retrospective study was conducted in 81 consecutive patients who had never received any botulinum toxin intradetrusor injections. They were treated with at least one 750 U intradetrusor injection of abobotulinum toxin A. All patients performed clean intermittent self catheterization (CIC) before injections. Success was defined as a combination of no incontinence episode, a number of catheterization <8 reported in a 3-day bladder diary and the lack of detrusor overactivity. RESULTS: Six weeks after the first injection, the success rate was 64.2 %. The proportion of continent patients was 80.2 %, the mean number of CIC per 24 h reduced (-3.55, p < 0.0001) and the mean catheterization volume increased (+237.3 ml, p < 0.0001). Regarding urodynamics, mean maximum cystometric capacity and mean volume at the first uninhibited contraction increased (+132.7 ml, p < 0.0001 and +180 ml, p < 0.0001, respectively) and mean maximum bladder pressure decreased significantly (-21.5 cm H2O, p < 0.0001). Mean reinjection number was 3.9 and mean interval between reinjection was 8.8 +/- 3 months. The clinical efficacy rate after each reinjection (up to fourteen) was at least 86.7 %. Out of 55 patients who underwent repeated injections, secondary resistance was noted in 2 (3.6 %). CONCLUSION: The results of the present study are in favor of a long-term safety and efficacy of abobotulinum toxin A 750 U for NDO. PMID- 26282100 TI - Molecular mechanisms of extracellular vesicle-induced vessel destabilization in diabetic retinopathy. AB - AIMS: Diabetic retinopathy (DR) is characterized by early dropout of capillary pericytes, leading to loss of control on endothelial proliferation and, subsequently, angiogenesis. We have demonstrated that extracellular vesicles (EV) derived from mesenchymal stem cells (MSC) maintained in diabetic-like conditions may play a role in vessel destabilization, thus contributing to angiogenesis through paracrine signalling. In particular, a role for MMP-2 was described. This study was aimed at further investigating the molecular mechanisms of EV-induced vessel destabilization. METHODS: We evaluated miR-126 expression, the subsequent HIF-1alpha and VEGF modulation, Ang-2 and PDGF signalling pathways in human retinal pericytes (HRP) after exposure to MSC-derived EV obtained in diabetic like conditions (high glucose and/or hypoxia). RESULTS: HRP express miR-126, and this expression is down-regulated in intermittent high glucose. MSC-derived EV obtained in hyperglycaemic/hypoxic conditions down-regulate miR-126 expression in pericytes, leading to increased expression of angiogenic molecules, such as VEGF and HIF-1alpha. No modulation of Ang-2 and PDGF signalling pathways in pericytes was observed following EV exposure. CONCLUSIONS: HRP express miR-126, and this expression is down-regulated in diabetic-like conditions. Exposure of HRP to EV obtained in diabetic-like conditions is able to decrease miR-126 expression, consistently with previous observations of its involvement in DR and providing further insights into the role of EV in vessel destabilization. In contrast, PDGF and Ang-2 signalling pathways do not seem to be involved in these mechanisms. PMID- 26282101 TI - Excision versus trichloroacetic acid (TCA) chemocauterization for branchial sinus of the pyriform fossa. AB - PURPOSE: We analyzed the outcomes of open surgical excision and endoscopic trichloroacetic acid (TCA) chemocauterization for the treatment of branchial sinus of the pyriform fossa (BSPF). METHOD: We retrospectively reviewed the records of 27 patients (16 males and 11 females) who were treated for BSPF at the Asan Medical Center between 1996 and 2013. RESULTS: The median age of the 27 patients was 4.5years (range, 0 to 15years). Before definitive surgery, 19 (70.3%) of the patients had histories of neck infection, and 16 (59.2%) patients had neck abscesses that were drained. The lesions were predominantly located on the left side (26 of 27; 96.2%). Excisions were performed for 14 (48.1%) patients. TCA chemocauterizations were performed for 13 patients. After a median follow-up period of 5.5years, 11 patients developed recurrence. The recurrence rates were not significantly different between the excision and chemocauterization groups (35.7% vs 46.1%, respectively, p=0.704). All of the recurred patients were successfully treated with repeated chemocauterization or reexcision. Analyses of the risk factors for recurrence revealed that a previous infection history tended to increase the rate of recurrence (90.9% vs 56.2%, p=0.090). CONCLUSION: Our experience suggests that the outcomes of excision and TCA chemocauterization are not significantly different. Additional studies are needed to reach a consensus regarding the best treatment strategy for BSPF. PMID- 26282102 TI - MRI-based relationships between spine pathology, intervertebral disc degeneration, and muscle fatty infiltration in chondrodystrophic and non chondrodystrophic dogs. AB - BACKGROUND CONTEXT: Human studies have revealed a link between muscle degeneration and low back pain, although the cause and effect of this relationship is not clear. Dogs provide a naturally developing model of intervertebral disc (IVD)-related low back pain that may provide insight into relationships between IVD and muscle degeneration. PURPOSE: This study aimed to quantify, via magnetic resonance imaging (MRI), the magnitude and location of fatty infiltration in spine muscles of chondrodystrophic (CD) and non chondrodystrophic (NCD) dogs suffering from both intervertebral disc herniation (IVDH) and non-disc-related spinal disorders, and relate this to intervertebral disc degeneration (IVDD). STUDY DESIGN: This study used retrospective MRI-based analysis of IVDD and muscle fatty infiltration in CD and NCD dogs. METHODS: A portion of this study was funded ($1,000) by the Pet Trust Fund, Ontario Veterinary College. Magnetic resonance imaging from 180 dogs were separated into four groups: (1) CD with IVDH; (2) CD with non-IVDH spinal pathology; (3) NCD with IVDH; (4) NCD with non-IVDH spinal pathology. For each dog at intervertebral levels T12-T13 to L6-L7, IVDD was subjectively graded and muscle-fat indices (MFIndices) were quantified for multifidus, erector spinae, and psoas muscle groups. RESULTS: Intervertebral disc degeneration grade was higher (p<.0001) for CD compared with NCD dogs, and for dogs diagnosed with IVDH compared with dogs with non-IVDH pathology. Muscle-fat indices of multifidus and psoas were higher (p<.01), indicating greater fatty infiltration, for NCD compared with CD dogs, and for dogs with non-IVDH pathology compared with dogs with IVDH. Erector spinae demonstrated higher (p<.0001) MFIndices compared with multifidus and psoas; however, this level of fatty infiltration was not dependent upon breed or pathology. CONCLUSIONS: Dog groups with higher average IVDD grades demonstrated less fatty infiltration within their multifidus and psoas muscles, compared with groups with lower IVDD grades. This finding was consistent across both CD and NCD breeds as well as across dogs presenting with IVDH and those presenting with a non-IVDH spinal pathology. Thus, the presence or severity of IVDD is not uniquely related to fatty infiltration in these muscles, but rather the presence, or possibly severity or chronicity, of general spine pathology is likely a better predictor of fatty infiltration. PMID- 26282103 TI - Classification of patients with incident non-specific low back pain: implications for research. AB - BACKGROUND CONTEXT: Comparing research studies of low back pain is difficult because of heterogeneity. There is no consensus among researchers on inclusion criteria or the definition of an episode. PURPOSE: This study aimed to determine pattern(s) of recurrent non-specific low back pain from data collected over 27 months. STUDY DESIGN/SETTING: This study used retrospective cohort study using administrative claims from multiple payers. Although claims are designed for capturing costs, not clinical complexity, they are valid for describing utilization patterns, which are not affected by potential "upcoding." PATIENT SAMPLE: The patient sample consisted of population-based, nationally generalizable sample of 65,790 adults with continuous medical and pharmaceutical commercial health insurance who received health care for incident, non-specific low back pain. Potential subjects were excluded for plausible cause of the pain, severe mental illness, or cognitive impairment. OUTCOME MEASURES: Diagnostic and therapeutic health-care services, including medical, surgical, pharmaceutical, and complementary, received in inpatient, outpatient, and emergency settings were the outcome measures for this study. METHODS: The methods used for this study were latent class analysis of health-care utilization over 27 months (9 quarters) following index diagnosis of non-specific low back pain occurring in January March 2009 and an analysis sample with 60% of subjects (n=39,597) and validation sample of 40% (n=26,193). RESULTS: Four distinct groups of patients were identified and validated. One group (53.4%) of patients recovered immediately. One third of patients (31.7%) may appear to recover over 6 months, but maintain a 37-48% likelihood of receiving care for low back pain in every subsequent quarter, implying frequent relapse. Two remaining groups of patients each maintain very high probabilities of receiving care in every quarter (65-78% and 84-90%), predominantly utilizing therapeutic services and pain medication, respectively. Probabilistic grouping relative to alternatives was very high (89.6 99.3%). Grouping was not related to demographic or clinical characteristics. CONCLUSIONS: The four distinct sets of patient experiences have clear implications for research. Inclusion criteria should specify incident or recurrent cases. A 6-month clean period may not be sufficiently long to assess incidence. Reporting should specify the proportion recovering immediately to prevent mean recovery rates from masking between-group differences. Continuous measurement of pain or disability may be more reliable than measuring outcomes at distinct endpoints. PMID- 26282104 TI - The relationship between the Tampa Scale of Kinesiophobia and low back pain rehabilitation outcomes. AB - BACKGROUNDCONTEXT: The Tampa Scale for Kinesiophobia (TSK) is commonly used in clinical practice to quantify levels of pain-related fear of activity or re injury in patients presenting with back pain. Patients with high levels of kinesiophobia are often considered at greater risk of developing long-term activity limitation and chronicity. There is, however, little evidence to support this assumption. PURPOSE: The purpose of this study was to assess the role of the TSK in determining eventual outcome in a cohort of low back pain patients completing a multidisciplinary rehabilitation program. STUDY DESIGN/SETTING: A prospective cohort study was used. PATIENT SAMPLE: The sample consisted of 313 low back pain patients treated at one of six rehabilitation clinics in New Zealand over a 4-year period. OUTCOME MEASURES: The outcome measures for this study are the TSK, Numeric Pain Scale (NPS), Modified Low Back Outcome Score (m LBOS), and vocational status (working or not working). METHODS: TSK questionnaire scores and three additional quality of life (QoL) measures (NPS, m-LBOS, and vocational status) were recorded at the initial assessment and after a 6- to 12 week period of rehabilitation. Statistical analysis was performed to determine the relationships between TSK scores and the QoL values recorded at initial assessment and postrehabilitation checkpoints. RESULTS: The correlations between initial TSK, NPS, and m-LBOS values recorded at assessment were statistically significant, but the relationships were weak. More importantly, there was no correlation between baseline TSK scores and changes in the numeric pain rating, perceived function, or vocational status after a period of rehabilitation. Correlations between changes in TSK scores and changes in NPS and m-LBOS values after rehabilitation were statistically significant, but the relationships were weak. CONCLUSIONS: The TSK provides no benefit as a screening tool to predict pain, functional and work outcomes following rehabilitation. Measured changes in TSK scores following rehabilitation do not correlate strongly with similar, concordant changes in pain scores, functional levels, or return-to-work outcomes. PMID- 26282105 TI - Influence of graft size on spinal instability with anterior cervical plate fixation following in vitro flexion-distraction injuries. AB - BACKGROUND CONTEXT: Anterior cervical discectomy and fusion with plating (ACDFP) is commonly used for the treatment of distractive-flexion cervical spine injuries. Despite the prevalence of ACDFP, there is little biomechanical evidence for graft height selection in the unstable trauma scenario. PURPOSE: This study aimed to investigate whether changes in graft height affect the kinematics of instrumented ACDFP C5-C6 motion segments in the context of varying degrees of simulated facet injuries. STUDY DESIGN: In vitro cadaveric biomechanical study was used as study design. METHODS: Seven C5-C6 motion segments were mounted in a custom spine simulator and taken through flexibility testing in axial rotation, lateral flexion, and flexion-extension. Specimens were first tested intact, followed by a standardized injury model (SIM) for a unilateral facet perch at C5 C6. The stability of the ACDFP approach was then examined with three graft heights (computed tomography-measured disc space height, disc space height undersized by 2.5 mm, and disc space height oversized by 2.5 mm) within three increasing unstable injuries (SIM, an added unilateral facet fracture, and a simulated bilateral facet dislocation injury). RESULTS: In all motions, regardless of graft size, ACDFP reduced range of motion (ROM) from the SIM state. For flexion-extension, the oversized graft had a larger decrease in ROM compared with the other graft sizes (p<.05). Between graft sizes and injury states, there were a number of interactions in axial rotation and lateral flexion, where specifically in the most severe injury, the undersized graft had a larger decrease in ROM than the other two sizes (p<.05). CONCLUSIONS: This study found that graft size did affect the kinematic stability of ACDFP in a series of distractive-flexion injuries; the undersized graft resulted in both facet overlap and locking of the uncovertebral joints leading to decreased ROM in lateral bending and axial rotation, whereas an oversized graft provided larger ROM decreases in flexion-extension. As such, a graft that engages the uncovertebral joint may be more advantageous in providing a rigid environment for fusion with ACDFP. PMID- 26282106 TI - Primary stability of three different iliosacral screw fixation techniques in osteoporotic cadaver specimens-a biomechanical investigation. AB - BACKGROUND: The incidence of osteoporotic and insufficiency fractures of the pelvic ring is increasing. Closed reduction and percutaneous fixation with cannulated sacroiliac screws is well-established in the operative treatment of osteoporotic posterior pelvic ring fractures. However, osteoporotic bone quality might lead to the risk of screw loosening. For this reason, cement augmentation of the iliosacral screws is more frequently performed and recommended. PURPOSE: The aim of the present biomechanical study was to evaluate the primary stability of three methods of iliosacral screw fixation in human osteoporotic sacrum specimens. STUDY DESIGN/SETTING: This study used methodical cadaver study. METHODS: A total of 15 fresh frozen human cadaveric specimens with osteoporosis were used (os sacrum). After matched pair randomization regarding bone quality (T score), three operation technique groups were generated: screw fixation (cannulated screws) without cement augmentation (Group A); screw fixation with cement augmentation before screw placement (cannulated screws) (Group B); and screw fixation with perforated screws and cement augmentation after screw placement (Group C). In all specimens both sides of the os sacrum were used for operative treatment, resulting in a group size of 10 specimens per group. One operation technique was used on each side of the sacral bone to compare biomechanical properties in the same bone quality. Pull-out tests were performed with a rate of 6 mm/min. A load versus displacement curve was generated. RESULTS: Subgroup 1 (Group A vs. Group B): Screw fixation without cement augmentation: 594.4 N+/-463.7 and screw fixation with cement augmentation before screw placement: 1,020.8 N+/-333.3; values were significantly different (p=.025). Subgroup 2 (Group A vs. Group C): Screw fixation without cement augmentation: 641.8 N+/-242.0 and perforated screw fixation with cement augmentation after screw placement: 1,029.6 N+/-326.5; values were significantly different (p=.048). Subgroup 3 (Group B vs. Group C): Screw fixation with cement augmentation before screw placement: 804.0 N+/-515.3 and perforated screw fixation with cement augmentation after screw placement: 889.8 N+/-503.3; values were not significantly different (p=.472). CONCLUSIONS: Regarding iliosacral screw fixation in osteoporotic bone, the primary stability of techniques involving cement augmentation is significantly higher compared with screw fixation without cement augmentation. Perforated screws with the same primary stability as that of conventional screw fixation in combination with cement augmentation might be a promising alternative in reducing complications of cement leakage. These biomechanical results have to be transferred into clinical practice and prove their clinical value. PMID- 26282107 TI - Gender differences in mortality among treated opioid dependent patients. AB - AIMS: To assess gender differences in characteristics, mortality rates, and the causes and predictors of death among treated opioid-dependent individuals. METHODS: Linked vital statistics data were obtained for all individuals first enrolled in publicly funded pharmacological treatment for opioid dependence in California from 2006 to 2010. Standardized mortality ratios (SMR) were calculated by gender. Cox proportional hazards models with time-varying covariates were fitted to determine the effect of gender on the hazard of all-cause mortality, controlling for covariates. RESULTS: Over a median 2.6 years (interquartile range: 1.4-3.7), 1.031 deaths were observed, including 2.2% (259/11,564) of women and 3.7% (772/20,758) of men. Women had a greater increased risk of mortality compared to the general population (SMR 5.1 95% CI: 4.5, 5.7) than men (SMR 4.3 95% CI: 4.0, 4.6). The relative risk of death for women compared with men was 1.18 (95% CI: 1.02, 1.36). Women had a lower instantaneous hazard of all-cause mortality than men (HR 0.58, 95% CI 0.50, 0.68), controlling for other factors. Significant interaction effects indicated that among men, mortality risk was decreased by full-time employment and increased by non-daily heroin use (relative to daily use) and medical problems. Concurrent opioid and methamphetamine/cocaine use increased mortality risk among women and decreased it among men. CONCLUSIONS: Treatment for opioid dependence is likely to reduce mortality risk among men by addressing employment and medical problems, and via interventions to reduce overdose risk after heroin abstinence, and among women by attending to the concurrent use of methamphetamine/cocaine and opioids. PMID- 26282108 TI - Trends and socioeconomic differences in policy triggers for thinking about quitting smoking: Findings from the International Tobacco Control (ITC) Europe Surveys. AB - INTRODUCTION: The aim of the current study is to investigate trends and socioeconomic differences in policy triggers for thinking about quitting in six European countries. METHODS: Data were derived from all available survey waves of the International Tobacco Control (ITC) Europe Surveys (2003-2013). France conducted three survey waves (n=1420-1735), Germany three waves (n=515-1515), The Netherlands seven waves (n=1420-1668), Ireland three waves (n=582-1071), Scotland two waves (n=461-507), and the rest of the United Kingdom conducted seven survey waves (n=861-1737). Smokers were asked whether four different policies (cigarette price, smoking restrictions in public places, free or lower cost medication, and warning labels on cigarette packs) influenced them to think about quitting. Generalized Estimating Equation (GEE) models were estimated for each country. RESULTS: Cigarette price was mentioned most often in all countries and across all waves as trigger for thinking about quitting. Mentioning cigarette price and warning labels increased after the implementation of price increases and warning labels in some countries, while mentioning smoking restrictions decreased after their implementation in four countries. All studied policy triggers were mentioned more often by smokers with low and/or moderate education and income than smokers with high education and income. The education and income differences did not change significantly over time for most policies and in most countries. CONCLUSIONS: Tobacco control policies work as a trigger to increase thoughts about quitting, particularly in smokers with low education and low income and therefore have the potential to reduce health inequalities in smoking. PMID- 26282109 TI - The use of psychoactive prescription drugs among DUI suspects. AB - BACKGROUND: The study seeks to increase understanding of the use of psychoactive prescription drugs among persons suspected of driving under the influence (DUI). We studied whether the use of prescribed psychoactive medication was associated with DUI, and examined the difference in the use of prescription drugs between DUI recidivists and those arrested only once. METHODS: In this register-based study, persons suspected of DUI (n=29470) were drawn from the Register of DUI suspects, and an age- and gender-matched reference population (n=30043) was drawn from the Finnish general population. Data on prescription drug use was obtained by linkage to the National Prescription Register. The associations of DUI arrest and use of psychoactive prescription drugs in different DUI groups (findings for alcohol only, prescription drugs, prescription drugs and alcohol, illicit drugs) were estimated by using mixed-effect logistic regression. RESULTS: The use of psychoactive prescription drugs and DUI appeared to be strongly associated, with DUI suspects significantly more likely to use psychoactive prescription drugs compared to the reference population. Gender differences existed, with the use of benzodiazepines being more common among female DUI suspects. Moreover, DUI recidivists were more likely to use psychoactive prescription drugs compared to those arrested only once. CONCLUSIONS: In addition to alcohol and/or illicit drug use, a significant proportion of DUI suspects were using psychoactive prescription drugs. When prescribing psychoactive medication, especially benzodiazepines, physicians are challenged to screen for possible substance use problems and also to monitor for patients' alcohol or illicit drug use while being medicated. PMID- 26282110 TI - Systematic chromatin state comparison of epigenomes associated with diverse properties including sex and tissue type. AB - Epigenomic data sets provide critical information about the dynamic role of chromatin states in gene regulation, but a key question of how chromatin state segmentations vary under different conditions across the genome has remained unaddressed. Here we present ChromDiff, a group-wise chromatin state comparison method that generates an information-theoretic representation of epigenomes and corrects for external covariate factors to better isolate relevant chromatin state changes. By applying ChromDiff to the 127 epigenomes from the Roadmap Epigenomics and ENCODE projects, we provide novel group-wise comparative analyses across sex, tissue type, state and developmental age. Remarkably, we find that distinct sets of epigenomic features are maximally discriminative for different group-wise comparisons, in each case revealing distinct enriched pathways, many of which do not show gene expression differences. Our methodology should be broadly applicable for epigenomic comparisons and provides a powerful new tool for studying chromatin state differences at the genome scale. PMID- 26282112 TI - Reducing pawing in horses using positive reinforcement. AB - Aversive control is a common method to reduce undesirable behavior in horses. However, it often results in unintended negative side effects, including potential abuse of the animal. Procedures based on positive reinforcement, such as differential reinforcement of other behavior (DRO), may reduce undesirable behaviors with fewer negative consequences. The current study used DRO schedules to reduce pawing using a multiple baseline design across 3 horses. Results indicated that DRO schedules were effective at reducing pawing. However, individual differences in sensitivity to DRO and reinforcer efficacy may be important considerations. PMID- 26282111 TI - Relationship between body mass index and left atrial appendage thrombus in nonvalvular atrial fibrillation. AB - Atrial fibrillation and obesity are two major growing epidemics in the United States and globally. Obese people are at the increased risk of developing atrial fibrillation. The contribution of obesity as an independent risk factor for stroke in the setting of atrial fibrillation remains unclear. We tested the hypothesis that non-valvular atrial fibrillation (NVAF) patients with increased body mass index (BMI) would be at increased risk for the development of left atrial appendage thrombus (LAAT). Consecutive, anticoagulation naive patients with NVAF referred for a transesophageal echocardiogram (TEE) between January 1, 2007 and October 21, 2009 were approached for study participation. All clinical, laboratory, and TEE measurement data were collected prospectively. Within a group of 400 anticoagulation naive NVAF patients (mean age 63 +/- 15 years, 28 % women; 17 % with LAAT) the prevalence of LAAT was similar across all BMI categories (normal 13 %, overweight 19 %, obese 16 %, morbidly obese 16 %; p = 0.71). Despite a higher CHADS2 score and a higher prevalence of both hypertension and diabetes mellitus, elevated BMI was not an independent predictor of LAAT when analyzed as either a continuous variable, across BMI WHO categories, a dichotomous variable stratified at values above versus below 27 kg/m(2), or BMI stratified on atrial fibrillation duration. Despite a higher prevalence of major risk factors for thromboembolism, the prevalence of LAAT was not increased in overweight, obese, and morbidly obese patients. PMID- 26282114 TI - Insights into the formation of chiral second sphere coordination complexes with aromatic tris amines: combined single crystal X-ray crystallography and molecular modeling analyses. AB - A family of isostructural, chiral supramolecular networks have been obtained in the solid state by exploiting second sphere coordination interactions in the self assembly of achiral tris amines and with tetrahalometallate and halide ions. Quantum-Mechanical (QM) calculations specific for solid phases provided additional insights into the intramolecular and packing interactions which determine chirality, pointing to a direct effect of the methyl groups of the central benzene ring. PMID- 26282113 TI - Up-regulation of PSMB4 is associated with neuronal apoptosis after neuroinflammation induced by lipopolysaccharide. AB - Proteasomes are major intracellular extralysosomal organelle for protein degradation and a central source of antigenic peptides in the endogenous pathway. Proteasome beta-4 subunit (PSMB4) was recently identified as potential cancer driver genes in several tumors. However, information regarding its regulation and possible function in the central nervous system is still limited. The present study was designed to elucidate dynamic changes in PSMB4 expression and distribution in the cerebral cortex in a lipopolysaccharide (LPS)-induced neuroinflammation rat model. It was found that PSMB4 expression was increased significantly in apoptotic neurons in the brain cortex after LPS injection. Moreover, there was a concomitant up-regulation of active caspase-3, cyclin D1, and CDK4 in vivo and vitro studies. In addition, these three proteins in cortical primary neurons were decreased after knocking down PSMB4 by siRNA. Collectively, these results suggested that PSMB4 may be involved in neuronal apoptosis in neuroinflammation after LPS injection. PMID- 26282115 TI - Principles of shared decision-making within teams. AB - In the domain of paediatric and congenital cardiac care, the stakes are huge. Likewise, the care of these children assembles a group of "A+ personality" individuals from the domains of cardiac surgery, cardiology, anaesthesiology, critical care, and nursing. This results in an environment that has opportunity for both powerful collaboration and powerful conflict. Providers of healthcare should avoid conflict when it has no bearing on outcome, as it is clearly a squandering of individual and collective political capital. Outcomes after cardiac surgery are now being reported transparently and publicly. In the present era of transparency, one may wonder how to balance the following potentially competing demands: quality healthcare, transparency and accountability, and teamwork and shared decision-making. An understanding of transparency and public reporting in the domain of paediatric cardiac surgery facilitates the implementation of a strategy for teamwork and shared decision-making. In January, 2015, the Society of Thoracic Surgeons (STS) began to publicly report outcomes of paediatric and congenital cardiac surgery using the 2014 Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHSD) Mortality Risk Model. The 2014 STS-CHSD Mortality Risk Model facilitates description of Operative Mortality adjusted for procedural and patient-level factors. The need for transparency in reporting of outcomes can create pressure on healthcare providers to implement strategies of teamwork and shared decision-making to assure outstanding results. A simple strategy of shared decision-making was described by Tom Karl and was implemented in multiple domains by Jeff Jacobs and David Cooper. In a critical care environment, it is not unusual for healthcare providers to disagree about strategies of management of patients. When two healthcare providers disagree, each provider can classify the disagreement into three levels: * SDM Level 1 Decision: "We disagree but it really does not matter, so do whatever you desire!" * SDM Level 2 Decision: "We disagree and I believe it matters, but I am OK if you do whatever you desire!!" * SDM Level 3 Decision: "We disagree and I must insist (diplomatically and politely) that we follow the strategy that I am proposing!!!!!!" SDM Level 1 Decisions and SDM Level 2 Decisions typically do not create stress on the team, especially when there is mutual purpose and respect among the members of the team. SDM Level 3 Decisions are the real challenge. Periodically, the healthcare team is faced with such Level 3 Decisions, and teamwork and shared decision-making may be challenged. Teamwork is a learned behaviour, and mentorship is critical to achieve a properly balanced approach. If we agree to leave our egos at the door, then, in the final analysis, the team will benefit and we will set the stage for optimal patient care. In the environment of strong disagreement, true teamwork and shared decision-making are critical to preserve the unity and strength of the multi-disciplinary team and simultaneously provide excellent healthcare. PMID- 26282117 TI - A cost-effective fluorescence mini-microscope for biomedical applications. AB - We have designed and fabricated a miniature microscope from off-the-shelf components and a webcam, with built-in fluorescence capability for biomedical applications. The mini-microscope was able to detect both biochemical parameters, such as cell/tissue viability (e.g. live/dead assay), and biophysical properties of the microenvironment such as oxygen levels in microfabricated tissues based on an oxygen-sensitive fluorescent dye. This mini-microscope has adjustable magnifications from 8-60*, achieves a resolution as high as <2 MUm, and possesses a long working distance of 4.5 mm (at a magnification of 8*). The mini-microscope was able to chronologically monitor cell migration and analyze beating of microfluidic liver and cardiac bioreactors in real time, respectively. The mini microscope system is cheap, and its modularity allows convenient integration with a wide variety of pre-existing platforms including, but not limited to, cell culture plates, microfluidic devices, and organs-on-a-chip systems. Therefore, we envision its widespread application in cell biology, tissue engineering, biosensing, microfluidics, and organs-on-chips, which can potentially replace conventional bench-top microscopy where long-term in situ and large-scale imaging/analysis is required. PMID- 26282119 TI - Myelin plasticity in the central nervous system. AB - Myelin sheaths, specialized segments of oligodendrocyte (OL) plasma membranes in the central nervous system (CNS), facilitate fast, saltatory conduction of action potentials down axons. Changes to the fine structure of myelin in a neural circuit, including sheath thickness and internode length (length of myelin segments between nodes of Ranvier), are expected to affect conduction velocity of action potentials. Myelination of the mammalian CNS occurs in a stereotyped, progressive pattern and continues well into adulthood in humans. Recent evidence from zebrafish, rodents, non-human primates, and humans suggests that myelination may be sensitive to experiences during development and adulthood, and that varying levels of neuronal activity may underlie these experience-dependent changes in myelin and myelin-forming cells. Several cellular, molecular, and epigenetic mechanisms have been investigated as contributors to myelin plasticity. A deeper understanding of myelin plasticity and its underlying mechanisms may provide insights into diseases involving myelin damage or dysregulation. This article is part of the Special Issue entitled 'Oligodendrocytes in Health and Disease'. PMID- 26282118 TI - Small molecule TrkB agonist deoxygedunin protects nigrostriatal dopaminergic neurons from 6-OHDA and MPTP induced neurotoxicity in rodents. AB - Dopaminergic neurons loss in the substantia nigra (SN) and dopamine (DA) content loss in the striatum correlate well with disease severity in Parkinson's disease (PD). Brain-derived neurotrophic factor (BDNF) is a member of neurotrophin family and is necessary for the survival and development of DA neurons in the SN. Deficits in BDNF/TrkB receptors signaling contribute to the dysfunction of PD. Deoxygedunin, a derivative of gedunin produced from Indian neem tree, binds TrkB receptor and activates TrkB and its downstream signaling cascades in a BDNF independent manner, and possesses neuroprotective effects in vitro and in vivo. In this study, we tested the neuroprotective effects of deoxygedunin in 6 hydroxydopamine (6-OHDA)-lesioned rat model and 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-induced mice model of Parkinson's disease. Rats were treated with deoxygedunin 5 mg/kg (i.p.) for one month started two weeks before 6 OHDA lesion (pre-treatment), or for two weeks right after lesion (post treatment), with isovolumetric vehicle as control and normal. Mice were given deoxygedunin 5 mg/kg (i.p.) for 2 weeks and administrated with MPTP twice at the dose of 20 mg/kg (i.p.) on day 7. The results revealed that pretreatment with deoxygedunin improved PD models' behavioral performance and reduced dopaminergic neurons loss in SN, associated with the activation of TrkB receptors and its two major signaling cascades involving mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K). Thus, our current study indicates that deoxygedunin, as a small molecule TrkB agonist, displays prominent neuroprotective properties, providing a novel therapeutic strategy for treating Parkinson's disease. PMID- 26282120 TI - Histamine and histamine receptors in Tourette syndrome and other neuropsychiatric conditions. AB - The potential contributions of dysregulation of the brain's histaminergic modulatory system to neuropsychiatric disease, and the potential of histamine targeting medications as therapeutic agents, are gradually coming into focus. The H3R receptor, which is expressed primarily in the central nervous system, is a promising pharmacotherapeutic target. Recent evidence for a contribution of histamine dysregulation to Tourette syndrome and tic disorders is particularly strong; although specific mutations in histamine-associated genes are rare, they have led to informative studies in animal models that may pave the way for therapeutic advances. A controlled study of an H3R antagonist in Tourette syndrome is ongoing. Preclinical studies of H3R antagonists in schizophrenia, attention deficit disorder, and narcolepsy have all shown promise. Recently reported controlled studies have been disappointing in schizophrenia and attention deficit disorder, but the H3R antagonist pitolisant shows promise in the treatment of narcolepsy and excessive daytime sleepiness and is currently under regulatory review for these conditions. This article is part of the Special Issue entitled 'Histamine Receptors'. PMID- 26282121 TI - Enamel surface roughness of preferred debonding and polishing protocols. AB - OBJECTIVE: This study investigated the surface roughness of enamel after debonding and instrumentation with commonly used methods. METHODS: Part I: a survey was sent to active members of the American Association of Orthodontists to determine popular bonding, debonding, and polishing protocols. Part II: brackets were bonded to the buccal surface of 30 extracted human premolar teeth. After debonding, residual adhesive was removed with 12-, 16-, and 20-fluted titanium carbide burs as based upon the survey results. The teeth were scanned with a surface profilometer for surface roughness. Part III: the teeth were further polished using a Reliance Renew polishing point or a prophy cup with pumice and rescanned for surface roughness. RESULTS: Part I: the majority of respondents used a generic bracket-removing plier to remove fixed appliances (53%) and a high speed handpiece for adhesive removal (85%). The most popular bur was a 12-fluted carbide bur without water spray. The majority of respondents used pumice paste and/or Reliance Renew points after adhesive removal. Part II: there was a significant difference in enamel surface roughness when 12-, 16-, and 20-fluted carbide burs were compared via surface profilometry. Part III: further polishing with a Reliance Renew point or a prophy cup and pumice did not provide a significantly smoother surface. CONCLUSIONS: The results show large variation in debonding and polishing techniques. Creating a smooth enamel surface is equally possible with 12- or 20-fluted carbide burs. Further polishing with pumice and prophy cup or Renew point does not provide an enamel smoother surface. PMID- 26282122 TI - Associations between risk factors in childhood (12-13 years) and adulthood (48-49 years) and subclinical atherosclerosis: the Kaunas Cardiovascular Risk Cohort Study. AB - BACKGROUND: The data on the childhood determinants of adult cardiovascular disease (CVD) are lacking in populations of Eastern Europe that are characterised by substantially high CVD mortality. From a public health perspective, it is important to identify high-risk individuals as early as possible in order to have the greatest benefit of preventive interventions. The aim of this study was to evaluate the associations of childhood and adulthood traditional risk factors with subclinical atherosclerosis and arterial stiffness in a Lithuanian cohort followed up for 35 years. METHODS: The study cohort consisted of 380 adults aged 48-49 from Kaunas Cardiovascular Risk Cohort study, who were followed up since childhood (12-13 years). The baseline survey (1977) included blood pressure (BP) and anthropometric measurements and sexual maturity scale. In the follow-up survey (2012), BP, anthropometric and lipids measurements, interview about smoking, measurement of carotid intima-media thickness (IMT) and determination of pulse wave velocity (PWV) were performed. Two types of general linear models were applied to test the associations of childhood and adulthood risk factors with IMT and PWV. Model 1 included only childhood variables. In model 2, adulthood variables were added to childhood variables. RESULTS: In linear regression model with childhood variables childhood systolic BP (beta = 0.014; p = 0.016) and BMI (beta = 0.006; p = 0.003) were directly associated with IMT only in women. When adulthood variables were included into regression model, the association between childhood systolic BP and IMT remained significant (beta = 0.013; p = 0.021), while childhood BMI was not associated with IMT (beta = 0.003; p = 0.143). Additionally, association of adult smoking and IMT was found in women (beta = 0.033; p = 0.018). IMT of men was directly related to adult systolic BP (beta = 0.022; p = 0.018) and inversely to HDL cholesterol level (beta = -0.044; p = 0.021). PWV was directly associated only with adult systolic BP in both genders (beta = 0.729 for men and beta = 0.476 for women; p = 0.001). CONCLUSIONS: Sex differences in the associations between childhood and adulthood risk factors and subclinical atherosclerosis were found. The results of the study support efforts to reduce conventional risk factors both in childhood and adulthood for the primary prevention of atherosclerosis. PMID- 26282123 TI - Variability and pathogenicity of hepatitis E virus genotype 3 variants. AB - Infection with hepatitis E virus (HEV) can be clinically inapparent or produce symptoms and signs of hepatitis of varying severity and occasional fatality. This variability in clinical outcomes may reflect differences in host susceptibility or the presence of virally encoded determinants of pathogenicity. Analysis of complete genome sequences supports the division of HEV genotype 3 (HEV-3) variants into three major clades: 3ra comprising HEV isolates from rabbits, and 3efg and 3abchij comprising the corresponding named subtypes derived from humans and pigs. Using this framework, we investigated associations between viral genetic variability of HEV-3 in symptomatic and asymptomatic infections by comparing HEV-3 subgenomic sequences previously obtained from blood donors with those from patients presenting with hepatitis in the UK (54 blood donors, 148 hepatitis patients), the Netherlands (38 blood donors, 119 hepatitis patients), France (24 blood donors, 55 hepatitis patients) and Germany (14 blood donors, 36 hepatitis patients). In none of these countries was evidence found for a significant association between virus variants and patient group (P>0.05 Fisher's exact test). Furthermore, within a group of 123 patients in Scotland with clinically apparent HEV infections, we found no evidence for an association between variants of HEV-3 and disease severity or alanine aminotransferase level. The lack of detectable virally encoded determinants of disease outcomes in HEV-3 infection implies a more important role for host factors in its clinical phenotype. PMID- 26282124 TI - Munchausen syndrome revealed by subcutaneous limb emphysema: a case report. AB - INTRODUCTION: Limb subcutaneous emphysema secondary to a Munchausen syndrome represents a rare and severe entity because it involves the functional prognosis of the limb and vital prognosis of the patient. CASE PRESENTATION: We report the case of an 18-year-old Moroccan woman patient who presented to our hospital with a subcutaneous emphysema of the shoulder girdle and the right arm, caused by our patient. Treatment was aggressive, with a wide surgical debridement, parenteral antibiotic therapy and hyperbaric oxygen therapy. The results have been favorable. CONCLUSIONS: The correlation of anamnestic data and clinical and para clinical exams were essential for the diagnosis of Munchausen syndrome in this case. In this regard, we report a rare case of subcutaneous limb emphysema secondary to Munchausen syndrome. PMID- 26282125 TI - A new instrument for estimation of survival in elderly patients irradiated for metastatic spinal cord compression from breast cancer. AB - BACKGROUND: Elderly patients become more important in oncology. In this group, personalized treatment approaches taking into account survival prognoses and comorbidities play a major role. Predictive instruments are necessary to estimate the survival of elderly cancer patients. The importance of separate instruments for different tumor entities has been recognized. In this study, an instrument was generated to estimate the survival of elderly patients developing metastatic spinal cord compression (MSCC) from breast cancer. METHODS: In 218 elderly patients (age >=65 years) irradiated for MSCC from breast cancer, nine factors were evaluated for survival: fractionation regimen, age, time from breast cancer diagnosis to RT of MSCC, visceral metastases, other bone metastases, time developing motor deficits, pre-radiotherapy ambulatory status, number of involved vertebrae, and Eastern Cooperative Oncology Group (ECOG) performance score. Factors significantly associated with survival in the Cox regression analysis were included in the prognostic instrument. Scores for each factor were calculated by dividing the 6-months survival rates by 10. The sums of these scores represented the patients' scores. RESULTS: On multivariate analyses, visceral metastases (p < 0.001), time developing motor deficits (p < 0.001), ambulatory status (p < 0.001), number of involved vertebrae (p = 0.032), and ECOG performance score (p < 0.001) were significant and included in the prognostic instrument. Based on the patients' scores, three groups were designed: 18-27 points, 28-39 points and 40-42 points. Six-months survival rates were 4, 62 and 100%, respectively (p < 0.001). CONCLUSIONS: This new instrument contributes to personalized treatment in elderly patients with MSCC from breast cancer by predicting an individual patient's survival prognosis. PMID- 26282126 TI - Depression in late adolescence: a cross-sectional study in senior high schools in Greece. AB - BACKGROUND: Depression is a common mental health problem in adolescents worldwide. The aim of the present study was to investigate the prevalence, comorbidity and sociodemographic and socioeconomic associations of depression and depressive symptoms, as well as the relevant health services use in a sample of adolescents in Greece. METHODS: Five thousand six hundred fourteen adolescents aged 16-18 years old and attending 25 senior high schools were screened and a stratified random sample of 2,427 were selected for a detailed interview. Psychiatric morbidity was assessed with a fully structured psychiatric interview, the revised Clinical Interview Schedule (CIS-R). The use of substances, such as alcohol, nicotine and cannabis, and several sociodemographic and socioeconomic variables have been also assessed. RESULTS: In our sample the prevalence rates were 5.67 % for the depressive episode according to ICD-10 and 17.43 % for a broader definition of depressive symptoms. 49.38 % of the adolescents with depressive episode had at least one comorbid anxiety disorder [OR: 7.76 (5.52 10.92)]. Only 17.08 % of the adolescents with depression have visited a doctor due to a psychological problem during the previous year. Anxiety disorders, substance use, female gender, older age, having one sibling, and divorce or separation of the parents were all associated with depression. In addition, the presence of financial difficulties in the family was significantly associated with an increased prevalence of both depression and depressive symptoms. CONCLUSIONS: Prevalence and comorbidity rates of depression among Greek adolescents are substantial. Only a small minority of depressed adolescents seek professional help. Significant associations with financial difficulties are reported. PMID- 26282127 TI - The evolutionary dynamics of tRNA-gene copy number and codon-use in E. coli. AB - BACKGROUND: The introduction of foreign DNA by Lateral Gene Transfer (LGT) can quickly and drastically alter genome composition. Problems can arise if the genes introduced by LGT use codons that are not suited to the host's translational machinery. Here we investigate compensatory adaptation of E. coli in response to the introduction of large volumes of codons that are rarely used by the host genome. RESULTS: We analyze genome sequences from the E. coli/Shigella complex, and find that certain tRNA genes are present in multiple copies in two pathogenic Shigella and O157:H7 subgroups of E. coli. Furthermore, we show that the codons that correspond to these multi-copy number tRNA genes are enriched in the high copy number Selfish Genetic Elements (SGE's) in Shigella and laterally introduced genes in O157:H7. We analyze the duplicate copies and find evidence for the selective retention of tRNA genes introduced by LGT in response to the changed codon content of the genome. CONCLUSION: These data support a model where the relatively rapid influx of LGT genes and SGE's introduces a large number of genes maladapted to the host's translational machinery. Under these conditions, it becomes advantageous for the host to retain tRNA genes that are required for the incorporation of amino acids at these codons. Subsequently, the increased number of copies of these specific tRNA genes adjusts the cellular tRNA pool to the demands set by global shifts in codon usage. PMID- 26282130 TI - Retraction for Leung et al., A Negative-Feedback Loop between the Detoxification/Antioxidant Response Factor SKN-1 and Its Repressor WDR-23 Matches Organism Needs with Environmental Conditions. PMID- 26282129 TI - Endothelial cells induce cancer stem cell features in differentiated glioblastoma cells via bFGF. AB - BACKGROUND: Glioblastoma multiforme (GBM) is a rapidly growing malignant brain tumor, which has been reported to be organized in a hierarchical fashion with cancer stem cells (CSCs) at the apex. Recent studies demonstrate that this hierarchy does not follow a one-way route but can be reverted with more differentiated cells giving rise to cells possessing CSC features. We investigated the role of tumor microvascular endothelial cells (tMVECs) in reverting differentiated glioblastoma cells to CSC-like cells. METHODS: We made use of primary GBM lines and tMVECs. To ensure differentiation, CSC-enriched cultures were forced into differentiation using several stimuli and cultures consisting solely of differentiated cells were obtained by sorting on the oligodendrocyte marker O4. Reversion to the CSC state was assessed phenotypically by CSC marker expression and functionally by evaluating clonogenic and multilineage differentiation potential. RESULTS: Conditioned medium of tMVECs was able to replenish the CSC pool by phenotypically and functionally reverting differentiated GBM cells to the CSC state. Basic fibroblast growth factor (bFGF), secreted by tMVECs, recapitulated the effects of the conditioned medium in inducing re-expression of CSC markers and increasing neurosphere formation ability of differentiated GBM cells. CONCLUSIONS: Our findings demonstrate that the CSC-based hierarchy displays a high level of plasticity showing that differentiated GBM cells can acquire CSC features when placed in the right environment. These results point to the need to intersect the elaborate network of tMVECs and GBM CSCs for efficient elimination of GBM CSCs. PMID- 26282128 TI - Catastrophic health expenditure and 12-month mortality associated with cancer in Southeast Asia: results from a longitudinal study in eight countries. AB - BACKGROUND: One of the biggest obstacles to developing policies in cancer care in Southeast Asia is lack of reliable data on disease burden and economic consequences. In 2012, we instigated a study of new cancer patients in the Association of Southeast Asian Nations (ASEAN) region - the Asean CosTs In ONcology (ACTION) study - to assess the economic impact of cancer. METHODS: The ACTION study is a prospective longitudinal study of 9,513 consecutively recruited adult patients with an initial diagnosis of cancer. Twelve months after diagnosis, we recorded death and household financial catastrophe (out-of-pocket medical costs exceeding 30% of annual household income). We assessed the effect on these two outcomes of a range of socio-demographic, clinical, and economic predictors using a multinomial regression model. RESULTS: The mean age of participants was 52 years; 64% were women. A year after diagnosis, 29% had died, 48% experienced financial catastrophe, and just 23% were alive with no financial catastrophe. The risk of dying from cancer and facing catastrophic payments was associated with clinical variables, such as a more advanced disease stage at diagnosis, and socioeconomic status pre-diagnosis. Participants in the low income category within each country had significantly higher odds of financial catastrophe (odds ratio, 5.86; 95% confidence interval, 4.76-7.23) and death (5.52; 4.34-7.02) than participants with high income. Those without insurance were also more likely to experience financial catastrophe (1.27; 1.05-1.52) and die (1.51; 1.21-1.88) than participants with insurance. CONCLUSIONS: A cancer diagnosis in Southeast Asia is potentially disastrous, with over 75% of patients experiencing death or financial catastrophe within one year. This study adds compelling evidence to the argument for policies that improve access to care and provide adequate financial protection from the costs of illness. PMID- 26282131 TI - Retraction for Leung et al., Direct Interaction between the WD40 Repeat Protein WDR-23 and SKN-1/Nrf Inhibits Binding to Target DNA. PMID- 26282133 TI - Harnessing Dynamic Covalent Bonds in Patchy Nanoparticles: Creating Shape Shifting Building Blocks for Rational and Responsive Self-Assembly. AB - Using computational modeling, we suggest and demonstrate a novel class of building blocks for nanoparticle self-assembly, that is, shape-shifting patchy nanoparticles. These nanoparticles are designed by harnessing dynamic covalent bonds between nanoparticles and patches decorated on them. The breaking and reforming of these bonds in response to their environment allow the patches to undergo a structural rearrangement that shifts the location or number of patches. Our simulations for the assembled superstructures and kinetic pathway of two types of these building blocks demonstrate that shape-shifting patchy nanoparticles delicately meet two emerging design concepts of next generation materials: rational self-assembly and responsive matter. In this context, these nanoparticles may enable new generations of materials with reconfigurable property as well as controllable topologies in a dynamical manner. PMID- 26282134 TI - Enhanced Electrocatalytic Properties of Transition-Metal Dichalcogenides Sheets by Spontaneous Gold Nanoparticle Decoration. AB - Here, we report that transition-metal dichalcogenides such as MoS2 and WS2 can be decorated with gold nanoparticles by a spontaneous redox reaction with hexachloroauric acid in water. The resulting gold nanoparticles tend to grow at defective sites, and therefore, selective decorations at the edges and the line defects in the basal planes of bulk single crystals were observed. The lithium intercalation-exfoliation process makes the basal planes of chemically exfoliated MoS2 and WS2 sheets much more defective than their single-crystalline counterparts, leading to a more uniform and higher-density deposition of gold nanoparticles. Due to the greatly improved charge transport between adjacent sheets, the resulting MoS2/Au and WS2/Au hybrids show significantly enhanced electrocatalytic performance toward hydrogen evolution reactions. PMID- 26282135 TI - Effect of Protonation State on the Stability of Amyloid Oligomers Assembled from TTR(105-115). AB - Amyloid fibrils are self-assembled aggregates of polypeptides that are implicated in the development of several human diseases. A peptide derived from amino acids 105-115 of the human plasma protein transthyretin forms homogeneous and well defined fibrils and, as a model system, has been the focus of a number of studies investigating the formation and structure of this class of aggregates. Self assembly of TTR(105-115) occurs at low pH, and this work explores the effect of protonation on the growth and stability of small cross-beta aggregates. Using molecular dynamics simulations of structures up to the decamer in both protonated and deprotonated states, we find that, whereas hexamers are more stable for protonated peptides, higher order oligomers are more stable when the peptides are deprotonated. Our findings imply a change in the acid pK of the protonated C terminal group during the formation of fibrils, which leads to stabilization of higher-order oligomers through electrostatic interactions. PMID- 26282136 TI - Confinement Effects on UV-Visible Absorption Spectra: beta-Carotene Inside Carbon Nanotube as a Test Case. AB - The effect of the confinement in a single-wall carbon nanotube on the optical properties of beta-carotene is studied at the time-dependent density functional theory level. A complex computational protocol has been developed, based on a multilayered ONIOM approach making use of a recent range-separated hybrid functional as well as dispersion corrections. The role of both mechanical and electronic embedding has been clearly pointed out, showing how the inclusion of the latter is mandatory for a correct description of the experimental data. The correct calculation of the bathochromic shift experimentally observed upon encapsulation (0.23 eV) shows the ability of this computational protocol to reproduce all the physics behind such a complex host-guest interaction. From a more chemical point of view, this study allows one to show how such a shift is related to both geometrical and polarization effects. PMID- 26282137 TI - Graphene Materials for Electrochemical Capacitors. AB - Electrochemical capacitors (ECs) have been widely applied in electronics, electric vehicles, aircrafts, energy storage devices, uninterrupted or emergency power supplies, and so on. An ideal EC should have high energy and/or powder density, good rate capability, and long cycling life. Recently, graphene, graphene derivatives, and their composites have been explored as the electrode materials of ECs to satisfy these requirements. In this Perspective, we review the recent development in synthesizing graphene materials for ECs and discuss the strategies of fabricating graphene-based macroscopic electrodes. Particularly, we highlight the importance of the specific surface area, conductivity, and heteroatom-doping of graphene sheets and the micro/nanostructures of their electrodes for controlling the performances of graphene-based ECs. PMID- 26282138 TI - Highly Active, Nonprecious Metal Perovskite Electrocatalysts for Bifunctional Metal-Air Battery Electrodes. AB - Perovskites are of great interest as replacements for precious metals and oxides used in bifunctional air electrodes involving the oxygen evolution reaction (OER) and oxygen reduction reaction (ORR). Herein, we report the synthesis and activity of a phase-pure nanocrystal perovskite catalyst that is highly active for the OER and ORR. The OER mass activity of LaNiO3, synthesized by the calcination of a rapidly dried nanoparticle dispersion and supported on nitrogen-doped carbon, is demonstrated to be nearly 3-fold that of 6 nm IrO2 and exhibits no hysteresis during oxygen evolution. Moreover, strong OER/ORR bifunctionality is shown by the low total overpotential (1.02 V) between the reactions, on par or better than that of noble metal catalysts such as Pt (1.16 V) and Ir (0.92 V). These results are examined in the context of surface hydroxylation, and a new OER cycle is proposed that unifies theory and the unique surface properties of LaNiO3. PMID- 26282139 TI - Microscopic Insights into the Electrochemical Behavior of Nonaqueous Electrolytes in Electric Double-Layer Capacitors. AB - Electric double-layer capacitors (EDLCs) are electrical devices that store energy by adsorption of ionic species at the inner surface of porous electrodes. Compared with aqueous electrolytes, ionic liquid and organic electrolytes have the advantage of larger potential windows, making them attractive for the next generation of EDLCs with superior energy and power densities. The performance of both ionic liquid and organic electrolyte EDLCs hinges on the judicious selection of the electrode pore size and the electrolyte composition, which requires a comprehension of the charging behavior from a microscopic view. In this Perspective, we discuss predictions from the classical density functional theory (CDFT) on the dependence of the capacitance on the pore size for ionic liquid and organic electrolyte EDLCs. CDFT is applicable to electrodes with the pore size ranging from that below the ionic dimensionality to mesoscopic scales, thus unique for investigating the electrochemical behavior of the confined electrolytes for EDLC applications. PMID- 26282140 TI - High-Energy Cathode Materials (Li2MnO3-LiMO2) for Lithium-Ion Batteries. AB - Lithium-rich layered oxide materials xLi2MnO3.(1-x)LiMO2 (M = Mn, Ni, Co, Fe, Cr, etc.) have attracted much attention for the use of cathode materials in lithium ion batteries in recent years. However, there are many issues still unclear (the structure and reaction mechanism are ambiguous until now), and numerous scientific challenges (low initial Coulombic efficiency, poor rate capability, and voltage degradation during cycling) of these materials that must be overcome to realize their utilization in commercial lithium-ion batteries. This Perspective focuses on the challenges and prospects associated with the current researching results of these lithium-rich layered cathode materials. Specifically, their average/local structures, reaction mechanisms, and electrochemical properties are discussed. PMID- 26282141 TI - Vanadium Flow Battery for Energy Storage: Prospects and Challenges. AB - The vanadium flow battery (VFB) as one kind of energy storage technique that has enormous impact on the stabilization and smooth output of renewable energy. Key materials like membranes, electrode, and electrolytes will finally determine the performance of VFBs. In this Perspective, we report on the current understanding of VFBs from materials to stacks, describing the factors that affect materials' performance from microstructures to the mechanism and new materials development. Moreover, new models for VFB stacks as well as structural design will be summarized as well. Finally, the challenges, the overall cost evaluation, and future research directions will be briefly proposed. PMID- 26282142 TI - In Charge of the World: Electrochemical Energy Storage. PMID- 26282143 TI - Acceptor-Enhanced Local Order in Conjugated Polymer Films. AB - Disorder in conjugated polymers is a general drawback that limits their use in organic electronics. We show that an archetypical conjugated polymer, MEH-PPV, enhances its local structural and electronic order upon addition of an electronic acceptor, trinitrofluorenone (TNF). First, acceptor addition in MEH-PPV results in a highly structured XRD pattern characteristic for semicrystalline conjugated polymers. Second, the surface roughness of the MEH-PPV films increases upon small acceptor addition, implying formation of crystalline nanodomains. Third, the low frequency Raman features of the polymer are narrowed upon TNF addition and indicate decreased inhomogeneous broadening. Finally, the photoinduced absorption and surface photovoltage spectroscopy data show that photoexcited and dark polymer intragap electronic states assigned to deep defects disappear in the blend. We relate the enhanced order to formation of a charge-transfer complex between MEH-PPV and TNF in the electronic ground state. These findings may be of high importance to control structural properties as they demonstrate an approach to increasing the order of a conjugated polymer by using an acceptor additive. PMID- 26282144 TI - Tailoring the Electronic Structure of Nanoelectrocatalysts Induced by a Surface Capping Organic Molecule for the Oxygen Reduction Reaction. AB - Capping organic molecules, including oleylamine, strongly adsorbed onto Pt nanoparticles during preparation steps are considered undesirable species for the oxygen reduction reaction due to decreasing electrochemical active sites. However, we found that a small amount of oleylamine modified platinum nanoparticles showed significant enhancement of the electrochemical activity of the oxygen reduction reaction, even with the loss of the electrochemically active surface area. The enhancement was correlated with the downshift of the frontier d band structure of platinum and the retardation of competitively adsorbed species. These results suggest that a capping organic molecule modified electrode can be a strategy to design an advanced electrocatalyst by modification of electronic structures. PMID- 26282145 TI - Identification of a Methane Oxidation Intermediate on Solid Oxide Fuel Cell Anode Surfaces with Fourier Transform Infrared Emission. AB - Fuel interactions on solid oxide fuel cell (SOFC) anodes are studied with in situ Fourier transform infrared emission spectroscopy (FTIRES). SOFCs are operated at 800 degrees C with CH4 as a representative hydrocarbon fuel. IR signatures of gas-phase oxidation products, CO2(g) and CO(g), are observed while cells are under load. A broad feature at 2295 cm(-1) is assigned to CO2 adsorbed on Ni as a CH4 oxidation intermediate during cell operation and while carbon deposits are electrochemically oxidized after CH4 operation. Electrochemical control provides confirmation of the assignment of adsorbed CO2. FTIRES has been demonstrated as a viable technique for the identification of fuel oxidation intermediates and products in working SOFCs, allowing for the elucidation of the mechanisms of fuel chemistry. PMID- 26282146 TI - Electronic Population Inversion in HCCO/DCCO Products from Hyperthermal Collisions of O((3)P) with HCCH/DCCD. AB - The dynamics of hyperthermal O((3)P) reactions with acetylene have been investigated with the use of crossed molecular beams techniques, employing both mass spectrometric and optical detection of products. With collision energies of 40-150 kcal mol(-1), O((3)P) + HCCH/DCCD -> HCCO/DCCO + H/D may follow multiple pathways to form the ketenyl radical (HCCO or DCCO) in ground doublet states or in electronically excited quartet and doublet states. Theoretical calculations support the assignment of the various reaction pathways. The fraction of electronic excitation is substantial. At the highest collision energy studied, ~65% of the ketenyl radical products that survive are electronically excited, with the majority of the excited products in a quartet state. In this case, a population inversion exists between the electronically excited quartet and ground doublet states of the ketenyl product. Such significant electronic excitation in products is unusual in bimolecular reactions, especially when ground-state products are accessible by spin-allowed pathways. PMID- 26282147 TI - Raman Optical Activity Probing Structural Deformations of the 4-Hydroxycinnamyl Chromophore in Photoactive Yellow Protein. AB - Many biological cofactors, such as light-absorbing chromophores in photoreceptors, contain a pi-electron system and are planar molecules. These cofactors are, however, usually nonplanar within a protein environment, and such structural distortions have been shown to be functionally important. Because the nonplanar structure makes the molecule chiral, Raman optical activity (ROA) provides a wealth of stereochemical information about the structural and conformational details of cofactors. The present study applied a near-infrared excited ROA to photoactive yellow protein, a blue light receptor. We successfully obtained the ROA spectra of the 4-hydroxycinnamyl chromophore embedded in a protein environment. Furthermore, calculations of the ROA spectra utilizing density functional theory provide detailed structural information, such as data on out-of-plane distortions of the chromophore. The structural information obtained from the ROA spectra includes the positions of hydrogen atoms, which are usually not detected in the crystal structures of biological samples. PMID- 26282148 TI - Intrinsic Charge Separation and Tunable Electronic Band Gap of Armchair Graphene Nanoribbons Encapsulated in a Double-Walled Carbon Nanotube. AB - Recent synthesis of nanocomposite structures of graphene nanoribbons (GNRs) encapsulated in a carbon nanotube (CNT) has opened a new avenue for exploring new functionalities for applications in nanotechnology. This new class of carbon nanocomposites is expected to possess electronic properties beyond those offered by the constituent parts of nanotubes and nanoribbons; unveiling such new properties and understanding the underlying physics are among the most pressing issues in the study of these promising materials. Here, we report on first principles calculations of the electronic properties of armchair GNRs encapsulated in a zigzag double-walled CNT. This unique structural configuration produces an intrinsic charge separation with electrons and holes localized in the outer tube and the ribbon, respectively, while the inner tube remains charge neutral, forming an n-type/intrinsic/p-type semiconducting heterojunction due to the staggered lineup of the band structures of the constituent parts. The electronic band gap of the nanocomposite can be tuned sensitively by the changing width of encapsulated GNRs. Such intrinsic charge separation and widely tunable electronic properties without doping or an external field make this class of new carbon nanocomposites promising candidates for photovoltaic and electronics applications. PMID- 26282149 TI - Interpretation of Cyclic Voltammetry Measurements of Thin Semiconductor Films for Solar Fuel Applications. AB - A simple model is proposed that allows interpretation of the cyclic voltammetry diagrams obtained experimentally for photoactive semiconductors with surface states or catalysts used for fuel production from sunlight. When the system is limited by charge transfer from the traps/catalyst layer and by detrapping, it is shown that only one capacitive peak is observable and is not recoverable in the return voltage scan. If the system is limited only by charge transfer and not by detrapping, two symmetric capacitive peaks can be observed in the cathodic and anodic directions. The model appears as a useful tool for the swift analysis of the electronic processes that limit fuel production. PMID- 26282150 TI - Electronic Structure of Semiconducting and Metallic Tubes in TiO2/Carbon Nanotube Heterojunctions: Density Functional Theory Calculations. AB - The electronic structure of the TiO2(110) surface interfaced with both a semiconducting and metallic carbon nanotube (CNT) was investigated by density functional theory. Our simulations rationalized visible light photocatalytic activity of CNT/TiO2 hybrid materials higher than that under ultraviolent irradiation and showed that the photoactivity of a semiconducting CNT decorating TiO2 is better than that of the metallic CNT/TiO2 system due to efficient charge separation across the interface. This suggests that semiconducting CNT/TiO2 could be a potential photovoltaic material. In contrast, strong interaction between a metallic CNT and TiO2 leads to large charge transfer. Such charge transfer reduces the built-in potential, in turn resulting in inefficient charge separation. Functionalizing the metallic CNT with a small platinum cluster can increase the built-in potential and drive charge separation. These observations indicate that the CNT/TiO2 interface can be a potential photovoltaic material by a metal cluster decorating a CNT despite a real tube being composed of the mixture of metallic and semiconducting CNTs. PMID- 26282151 TI - Inkjet Printing of High Conductivity, Flexible Graphene Patterns. AB - The ability to print high conductivity, conformal, and flexible electrodes is an important technological challenge in printed electronics, especially for large area formats with low cost considerations. In this Letter, we demonstrate inkjet printed, high conductivity graphene patterns that are suitable for flexible electronics. The ink is prepared by solution-phase exfoliation of graphene using an environmentally benign solvent, ethanol, and a stabilizing polymer, ethyl cellulose. The inkjet-printed graphene features attain low resistivity of 4 mOmega.cm after a thermal anneal at 250 degrees C for 30 min while showing uniform morphology, compatibility with flexible substrates, and excellent tolerance to bending stresses. PMID- 26282152 TI - Geometric Dependence of the Line Width of Localized Surface Plasmon Resonances. AB - For the same number of electrons and plasmon frequencies, longitudinal plasmon resonances in metallic nanorods exhibit narrower line widths than plasmon modes in spherical particles. We show that this property is a general feature of high aspect ratio nanostructures and can be explained very simply by incorporating retardation effects into a harmonic oscillator model. The origin of the effect is dynamic depolarization, which renormalizes the mass of the electrons and the oscillating electron liquid. The scattering spectrum derived from our model agrees very well with FDTD simulations. Because plasmon damping determines many important features and applications of LSPR, such as the Q factor of plasmonics devices and the magnitude of the induced field enhancements, our study will play an important role for the design of nanostructures with narrow plasmon resonances. PMID- 26282153 TI - Broad-Band Impulsive Vibrational Spectroscopy of Excited Electronic States in the Time Domain. AB - We demonstrate that transient absorption spectroscopy performed with an ultrashort pump pulse and a chirped, broad-band probe pulse is capable of recording full vibrational spectra of excited electronic states in the time domain. The resulting spectra do not suffer from the nontrivial baselines and line shapes often encountered in frequency domain techniques and enable optimal and automated subtraction of background signatures. Probing the molecular dynamics continuously over a broad energy bandwidth makes it possible to confidently assign the vibrational coherences to specific electronic states and suggests the existence of mode-specific absorption spectra reminiscent of resonance Raman intensity analysis. The first observation of the nominally forbidden one-photon ground to first excited electronic state transition in beta carotene demonstrates the high sensitivity of our approach. Our results provide a first glimpse of the immense potential of broad-band impulsive vibrational spectroscopy (BB-IVS) to study ultrafast chemical reaction dynamics. PMID- 26282154 TI - Surgical management of recurrent lumbar disc herniation and the role of fusion. AB - This systematic review was performed to evaluate the various operative management strategies for recurrent lumbar disc herniation (RLDH), including the efficacy of instrumented spinal fusion (ISF) at repeat discectomy, and whether the operative approach for repeat discectomy, minimally invasive (MID) or conventional open discectomy (CD), affected the outcomes. RLDH is one of the most common complications of lumbar discectomies. Whilst repeat discectomy is the standard procedure performed, the routine addition of ISF has been advocated to improve outcomes and prevent reherniation. A comprehensive search of the MEDLINE, EMBASE, CINAHL and Cochrane databases was performed. The measured outcomes included the rate of satisfactory clinical outcome, improvement in leg and back pain, Japanese Orthopaedic Association (JOA) recovery score, and complication rates. In total, 37 studies met our inclusion criteria, with 1483 patients. The rate of satisfactory outcomes was found to be statistically similar between the patients undergoing a discectomy with or without fusion (77.8% with ISF versus 79.5% without ISF; p=0.665). Back pain and JOA scores showed greater improvements in the patients undergoing discectomy and fusion, compared to discectomy alone. The rate of satisfactory outcomes was marginally higher in the patients undergoing MID compared to CD (MID 81.2% versus CD 77.5%; p=0.248). However, the leg pain improvement was similar. The postoperative back pain improvement was greater in the MID group (52.5% MID versus 36.3% CD), but with lower complication rates, specifically durotomies (MID 5.2% versus CD 15.3%; p<0.001). There is no evidence to recommend the routine addition of ISF in the management of RLDH. The data suggest that MID has lower complication rates than CD in the setting of RLDH, yet unequivocal evidence is lacking. PMID- 26282155 TI - Risk factors for surgical site infections following spinal surgery. AB - The aim of this study was to determine the risk factors for postoperative infection after spinal surgery, in order to prevent its occurrence. We searched the Pubmed, Embase, and Cochrane library databases, and identified 25 case control studies. The pooled results revealed that the major factors associated with infection were diabetes mellitus (odds ratio [OR] 2.04; 95% confidence interval [CI] 1.69-2.46), obesity (OR 2.13; 95% CI 1.55-2.93), smoking (OR 1.17; 95% CI 1.03-1.32), urinary tract infection (OR 3.19; 95% CI 1.68-6.06), hypertension (OR 1.67; 95% CI 1.26-2.22), transfusion (OR 3.64; 95% CI 2.60 5.08), and cerebrospinal fluid leak (OR 3.22; 95% CI 1.07-9.67). There was insufficient evidence to suggest that male sex, age, alcohol use, and steroid use increased the incidence of infection after spinal surgery. Our analyses suggest strategies to prevent surgical site infection. However, the results should be interpreted with caution because of heterogeneity amongst the included studies. PMID- 26282156 TI - [Not Available]. PMID- 26282157 TI - Vitamin D and calcium regulation of epidermal wound healing. AB - Wound healing is essential for survival. This is a multistep process involving a number of different cell types. In the skin wounding triggers an acute inflammatory response, with the innate immune system contributing both to protection against invasive organisms and to triggering the invasion of inflammatory cells into the wounded area. These cells release a variety of cytokines and growth factors that stimulate the proliferation and migration of dermal and epidermal cells to close the wound. In particular, wounding activates stem cells in the interfollicular epidermis (IFE) and hair follicles (HF) to proliferate and send their progeny to re-epithelialize the wound. beta-catenin and calcium signaling are important for this activation process. Mice lacking the VDR when placed on a low calcium diet have delayed wound healing. This is associated with reduced beta-catenin transcriptional activity and proliferation in the cells at the leading edge of wound closure. These data suggest that vitamin D and calcium signaling are necessary components of the epidermal response to wounding, likely by regulating stem cell activation through increased beta-catenin transcriptional activity. PMID- 26282158 TI - An Hourly Dose-Escalation Desensitization Protocol for Aspirin-Exacerbated Respiratory Disease. AB - BACKGROUND: Aspirin desensitization followed by maintenance therapy effectively improves symptom control in patients with aspirin exacerbated respiratory disease (AERD). The majority of current desensitization protocols use 3-hour dosing intervals and often require 2 to 3 days to complete. OBJECTIVE: We evaluated hourly dose escalations in a subset of patients with chronic rhinosinusitis, nasal polyps, and asthma who historically reacted to aspirin within 1 hour or were avoiding aspirin with the goal of developing a safe and efficient desensitization protocol. METHODS: Fifty-seven aspirin desensitizations were performed under the hourly protocol. All patients had refractory nasal polyposis as an indication for aspirin desensitization. The clinical characteristics of each subject were analyzed in relation to aspects of his or her reactions during the procedure. RESULTS: Ninety-eight percent of study patients were successfully treated under the hourly protocol, including those with a history of severe reactions and intubation. None required further medication than is available in an outpatient allergy clinic. A total of 96% of reactors recorded a bronchial or naso-ocular reaction within 1 hour of the preceding dose. Of the total patients on this protocol, 40% were able to complete the procedure in a single day, and 60% within 2 days. CONCLUSION: Patients with AERD who have a history of symptoms less than 1 hour after aspirin exposure can be safely desensitized with a 1-hour dose-escalation protocol that can often be completed in a single day. PMID- 26282159 TI - Anaphylaxis to oats after cutaneous sensitization by oatmeal in skin products used for the treatment of atopic dermatitis. PMID- 26282160 TI - Adherent uncontrolled adult persistent asthma: Characteristics and asthma outcomes. PMID- 26282162 TI - Evaluation of the Wilma-SIE Virtual Screening Method in Community Structure Activity Resource 2013 and 2014 Blind Challenges. AB - Prospective assessments of the Wilma-SIE (solvated interaction energy) platform for ligand docking and ranking were performed during the 2013 and 2014 editions of the Community Structure-Activity Resource (CSAR) blind challenge. Diverse targets like a steroid-binding protein, a serine protease (factor Xa), a tyrosine kinase (Syk), and a nucleotide methyltransferase (TrmD) were included. Pose selection was achieved with high precision; in all 24 tests Wilma-SIE top-ranked the native pose among carefully generated sets of decoy conformations. Good separation for the native pose was also observed indicating robustness in pose scoring. Cross-docking was also accomplished with high accuracy for the various systems, with ligand median-RMSD values around 1 A from the crystal structures. Larger deviations were occasionally obtained due to the rigid-target approach even if multiple target structures were used. Affinity ranking of congeneric ligands after cross-docking was reasonable for three of the four systems, with Spearman ranking coefficients around 0.6. Poor affinity ranking for FXa is possibly due to missing structural domains, which are present during measurements. Assignment of protonation states is critical for affinity scoring with the SIE function, as shown here for the Syk system. Including the FiSH model improved cross-docking but worsened affinity predictions, pointing to the need for further fine-tuning of this newer solvation model. The consistently strong performance of the Wilma-SIE platform in recent CSAR and SAMPL blind challenges validates its applicability for virtual screening on a broad range of molecular targets. PMID- 26282163 TI - Multi-chromatic magnetic resonance imaging using frequency lock-in suppression. AB - This study developed a multi-chromatic MR contrast using the frequency lock-in technique. An electronic feedback device that generates a specific narrow frequency-bandwidth RF field is presented. The effects of this RF field on MR images are assessed both theoretically and experimentally. Spectroscopy and imaging experiments were performed. Frequency tuning allowed the selected spectral peak to be suppressed. Phantom tests using methanol, ethanol, and water showed different contrasts using different feedback RF field frequencies. The frequency lock-in was also found to help differentiate among the small structural variations in biological tissues. The contrast achieved in in vivo mouse brain imaging using the lock-in suppressed technique indicated a better spatial discrimination when compared with that achieved using conventional imaging methods, especially in the hippocampus region. Selective lock-in suppressed imaging is a new approach to provide frequency information in MRI; rather than determining the evolution of image contrast over time, this approach allows small susceptibility variations to be distinguished by tuning the frequency of the narrow-bandwidth lock-in RF field. A new and enhanced contrast can be achieved using this technique. PMID- 26282164 TI - A supplementation of DHA and AA to human milk-fed VLBW infants has no significant cognitive improvement or measurable neuroanatomical effects when evaluated at 8 years of age. PMID- 26282166 TI - The miR-146b-3p/PAX8/NIS Regulatory Circuit Modulates the Differentiation Phenotype and Function of Thyroid Cells during Carcinogenesis. AB - The presence of differentiated thyroid cells in thyroid cancer is critical for the antitumor response to radioactive iodide treatment, and loss of the differentiated phenotype is a key hallmark of iodide-refractory metastatic disease. The role of microRNAs (miRNA) in fine-tuning gene expression has become a major regulatory mechanism by which developmental and pathologic processes occur. In this study, we performed next-generation sequencing and expression analysis of eight papillary thyroid carcinomas (PTC) to comprehensively characterize miRNAs involved in loss of differentiation. We found that only a small set of abundant miRNAs is differentially expressed between PTC tissue and normal tissue from the same patient. In addition, we integrated computational prediction of potential targets and mRNA sequencing and identified a master miRNA regulatory network involved in essential biologic processes such as thyroid differentiation. Both mature products of mir-146b (miR-146b-5p and -3p) were among the most abundantly expressed miRNAs in tumors. Specifically, we found that miR-146b-3p binds to the 3'-untranslated region of PAX8 and sodium/iodide symporter (NIS), leading to impaired protein translation and a subsequent reduction in iodide uptake. Furthermore, our findings show that miR-146b and PAX8 regulate each other and share common target genes, thus highlighting a novel regulatory circuit that governs the differentiated phenotype of PTC. In conclusion, our study has uncovered the existence of a miR-146b-3p/PAX8/NIS regulatory circuit that may be exploited therapeutically to modulate thyroid cell differentiation and iodide uptake for improved treatment of advanced thyroid cancer. PMID- 26282165 TI - STAT3 Blockade Inhibits Radiation-Induced Malignant Progression in Glioma. AB - High grade gliomas (HGG) are classified into four subgroups based on transcriptional signatures and phenotypic characteristics. In particular, the proneural-to-mesenchymal transition (PMT) is associated with increased malignancy, poor prognosis, and disease recurrence, but the underlying causes of PMT are still unclear. In this study, we investigated whether radiotherapy promotes PMT using a genetically engineered mouse model of proneural HGG. We found that cranial ionizing radiation induced robust and durable PMT in tumors. Additionally, we isolated primary proneural HGG cells from mouse and human tumors and demonstrate that radiation induced a sustained cell-intrinsic mesenchymal transition associated with increased invasiveness and resistance to the alkylating agent temozolomide. Expectedly, irradiation-induced PMT was also associated with activation of the STAT3 transcription factor, and the combination of STAT3 blockade using JAK2 inhibitors with radiation abrogated the mesenchymal transition and extended survival of mice. Taken together, our data suggest that clinical JAK2 inhibitors should be tested in conjunction with radiation in patients with proneural HGG as a new strategy for blocking the emergence of therapy-resistant mesenchymal tumors at relapse. PMID- 26282168 TI - High-Resolution Rapid Diagnostic Imaging of Whole Prostate Biopsies Using Video Rate Fluorescence Structured Illumination Microscopy. AB - Rapid assessment of prostate core biopsy pathology at the point-of-procedure could provide benefit in a variety of clinical situations. Even with advanced transrectal ultrasound guidance and saturation biopsy protocols, prostate cancer can be missed in up to half of all initial biopsy procedures. In addition, collection of tumor specimens for downstream histologic, molecular, and genetic analysis is hindered by low tumor yield due to inability to identify prostate cancer grossly. However, current point-of-procedure pathology protocols, such as frozen section analysis (FSA), are destructive and too time- and labor-intensive to be practical or economical. Ex vivo microscopy of the excised specimens, stained with fast-acting fluorescent histology dyes, could be an attractive nondestructive alternative to FSA. In this work, we report the first demonstration of video-rate structured illumination microscopy (VR-SIM) for rapid high-resolution diagnostic imaging of prostate biopsies in realistic point-of procedure timeframes. Large mosaic images of prostate biopsies stained with acridine orange are rendered in seconds and contain excellent contrast and detail, exhibiting close correlation with corresponding hematoxylin and eosin histology. A clinically relevant review of VR-SIM images of 34 unfixed and uncut prostate core biopsies by two independent pathologists resulted in an area under the receiver operative curve (AUC) of 0.82-0.88, with a sensitivity ranging from 63% to 88% and a specificity ranging from 78% to 89%. When biopsies contained more than 5% tumor content, the sensitivity improved to 75% to 92%. The image quality, speed, minimal complexity, and ease of use of VR-SIM could prove to be features in favor of adoption as an alternative to destructive pathology at the point-of-procedure. PMID- 26282167 TI - Hepatocyte Growth Factor/cMET Pathway Activation Enhances Cancer Hallmarks in Adrenocortical Carcinoma. AB - Adrenocortical carcinoma is a rare malignancy with poor prognosis and limited response to chemotherapy. Hepatocyte growth factor (HGF) and its receptor cMET augment cancer growth and resistance to chemotherapy, but their role in adrenocortical carcinoma has not been examined. In this study, we investigated the association between HGF/cMET expression and cancer hallmarks of adrenocortical carcinoma. Transcriptomic and immunohistochemical analyses indicated that increased HGF/cMET expression in human adrenocortical carcinoma samples was positively associated with cancer-related biologic processes, including proliferation and angiogenesis, and negatively correlated with apoptosis. Accordingly, treatment of adrenocortical carcinoma cells with exogenous HGF resulted in increased cell proliferation in vitro and in vivo while short hairpin RNA-mediated knockdown or pharmacologic inhibition of cMET suppressed cell proliferation and tumor growth. Moreover, exposure of cells to mitotane, cisplatin, or radiation rapidly induced pro-cMET expression and was associated with an enrichment of genes (e.g., CYP450 family) related to therapy resistance, further implicating cMET in the anticancer drug response. Together, these data suggest an important role for HGF/cMET signaling in adrenocortical carcinoma growth and resistance to commonly used treatments. Targeting cMET, alone or in combination with other drugs, could provide a breakthrough in the management of this aggressive cancer. PMID- 26282169 TI - Intratumoral Heterogeneity in EGFR-Mutant NSCLC Results in Divergent Resistance Mechanisms in Response to EGFR Tyrosine Kinase Inhibition. AB - Non-small cell lung cancers (NSCLC) that have developed resistance to EGF receptor (EGFR) tyrosine kinase inhibitor (TKI), including gefitinib and erlotinib, are clinically linked to an epithelial-to-mesenchymal transition (EMT) phenotype. Here, we examined whether modulating EMT maintains the responsiveness of EGFR-mutated NSCLCs to EGFR TKI therapy. Using human NSCLC cell lines harboring mutated EGFR and a transgenic mouse model of lung cancer driven by mutant EGFR (EGFR-Del19-T790M), we demonstrate that EGFR inhibition induces TGFbeta secretion followed by SMAD pathway activation, an event that promotes EMT. Chronic exposure of EGFR-mutated NSCLC cells to TGFbeta was sufficient to induce EMT and resistance to EGFR TKI treatment. Furthermore, NSCLC HCC4006 cells with acquired resistance to gefitinib were characterized by a mesenchymal phenotype and displayed a higher prevalence of the EGFR T790M mutated allele. Notably, combined inhibition of EGFR and the TGFbeta receptor in HCC4006 cells prevented EMT but was not sufficient to prevent acquired gefitinib resistance because of an increased emergence of the EGFR T790M allele compared with cells treated with gefitinib alone. Conversely, another independent NSCLC cell line, PC9, reproducibly developed EGFR T790M mutations as the primary mechanism underlying EGFR TKI resistance, even though the prevalence of the mutant allele was lower than that in HCC4006 cells. Thus, our findings underscore heterogeneity within NSCLC cells lines harboring EGFR kinase domain mutations that give rise to divergent resistance mechanisms in response to treatment and anticipate the complexity of EMT suppression as a therapeutic strategy. PMID- 26282171 TI - TIF1gamma Suppresses Tumor Progression by Regulating Mitotic Checkpoints and Chromosomal Stability. AB - The transcription accessory factor TIF1gamma/TRIM33/RFG7/PTC7/Ectodermin functions as a tumor suppressor that promotes development and cellular differentiation. However, its precise function in cancer has been elusive. In the present study, we report that TIF1gamma inactivation causes cells to accumulate chromosomal defects, a hallmark of cancer, due to attenuations in the spindle assembly checkpoint and the post-mitotic checkpoint. TIF1gamma deficiency also caused a loss of contact growth inhibition and increased anchorage-independent growth in vitro and in vivo. Clinically, reduced TIF1gamma expression in human tumors correlated with an increased rate of genomic rearrangements. Overall, our work indicates that TIF1gamma exerts its tumor-suppressive functions in part by promoting chromosomal stability. PMID- 26282173 TI - Selective Inhibition of Parallel DNA Damage Response Pathways Optimizes Radiosensitization of Glioblastoma Stem-like Cells. AB - Glioblastoma is the most common form of primary brain tumor in adults and is essentially incurable. Despite aggressive treatment regimens centered on radiotherapy, tumor recurrence is inevitable and is thought to be driven by glioblastoma stem-like cells (GSC) that are highly radioresistant. DNA damage response pathways are key determinants of radiosensitivity but the extent to which these overlapping and parallel signaling components contribute to GSC radioresistance is unclear. Using a panel of primary patient-derived glioblastoma cell lines, we confirmed by clonogenic survival assays that GSCs were significantly more radioresistant than paired tumor bulk populations. DNA damage response targets ATM, ATR, CHK1, and PARP1 were upregulated in GSCs, and CHK1 was preferentially activated following irradiation. Consequently, GSCs exhibit rapid G2-M cell-cycle checkpoint activation and enhanced DNA repair. Inhibition of CHK1 or ATR successfully abrogated G2-M checkpoint function, leading to increased mitotic catastrophe and a modest increase in radiation sensitivity. Inhibition of ATM had dual effects on cell-cycle checkpoint regulation and DNA repair that were associated with greater radiosensitizing effects on GSCs than inhibition of CHK1, ATR, or PARP alone. Combined inhibition of PARP and ATR resulted in a profound radiosensitization of GSCs, which was of greater magnitude than in bulk populations and also exceeded the effect of ATM inhibition. These data demonstrate that multiple, parallel DNA damage signaling pathways contribute to GSC radioresistance and that combined inhibition of cell-cycle checkpoint and DNA repair targets provides the most effective means to overcome radioresistance of GSC. PMID- 26282172 TI - Transcriptome Sequencing Reveals PCAT5 as a Novel ERG-Regulated Long Noncoding RNA in Prostate Cancer. AB - Castration-resistant prostate cancers (CRPC) that arise after the failure of androgen-blocking therapies cause most of the deaths from prostate cancer, intensifying the need to fully understand CRPC pathophysiology. In this study, we characterized the transcriptomic differences between untreated prostate cancer and locally recurrent CRPC. Here, we report the identification of 145 previously unannotated intergenic long noncoding RNA transcripts (lncRNA) or isoforms that are associated with prostate cancer or CRPC. Of the one third of these transcripts that were specific for CRPC, we defined a novel lncRNA termed PCAT5 as a regulatory target for the transcription factor ERG, which is activated in approximately 50% of human prostate cancer. Genome-wide expression analysis of a PCAT5-positive prostate cancer after PCAT5 silencing highlighted alterations in cell proliferation pathways. Strikingly, an in vitro validation of these alterations revealed a complex integrated phenotype affecting cell growth, migration, invasion, colony-forming potential, and apoptosis. Our findings reveal a key molecular determinant of differences between prostate cancer and CRPC at the level of the transcriptome. Furthermore, they establish PCAT5 as a novel oncogenic lncRNA in ERG-positive prostate cancers, with implications for defining CRPC biomarkers and new therapeutic interventions. PMID- 26282170 TI - A Quantitative System for Studying Metastasis Using Transparent Zebrafish. AB - Metastasis is the defining feature of advanced malignancy, yet remains challenging to study in laboratory environments. Here, we describe a high throughput zebrafish system for comprehensive, in vivo assessment of metastatic biology. First, we generated several stable cell lines from melanomas of transgenic mitfa-BRAF(V600E);p53(-/-) fish. We then transplanted the melanoma cells into the transparent casper strain to enable highly quantitative measurement of the metastatic process at single-cell resolution. Using computational image analysis of the resulting metastases, we generated a metastasis score, MU, that can be applied to quantitative comparison of metastatic capacity between experimental conditions. Furthermore, image analysis also provided estimates of the frequency of metastasis-initiating cells (~1/120,000 cells). Finally, we determined that the degree of pigmentation is a key feature defining cells with metastatic capability. The small size and rapid generation of progeny combined with superior imaging tools make zebrafish ideal for unbiased high-throughput investigations of cell-intrinsic or microenvironmental modifiers of metastasis. The approaches described here are readily applicable to other tumor types and thus serve to complement studies also employing murine and human cell culture systems. PMID- 26282174 TI - Enhanced Chemokine Receptor Recycling and Impaired S1P1 Expression Promote Leukemic Cell Infiltration of Lymph Nodes in Chronic Lymphocytic Leukemia. AB - Lymphocyte trafficking is orchestrated by chemokine and sphingosine 1-phosphate (S1P) receptors that enable homing and egress from secondary lymphoid organs (SLO). These receptors undergo rapid internalization and plasma membrane recycling to calibrate cellular responses to local chemoattractants. Circulating chronic lymphocytic leukemia (CLL) cells display an abnormal increase in the surface levels of the homing receptors CCR7 and CXCR4 concomitant with low S1P receptor 1 (S1P1) expression. In this study, we investigated the role of receptor recycling on CXCR4/CCR7 surface levels in CLL cells and addressed the impact of quantitative alterations of these receptors and S1P1 on the ability of leukemic cells to accumulate in SLOs. We show that recycling accounts, to a major extent, for the high levels of surface CXCR4/CCR7 on CLL cells. In addition, increased expression of these receptors, together with S1P1 deficiency, is detectable not only in circulating leukemic cells, but also in SLOs of CLL patients with lymphoadenopathy. We further provide evidence that ibrutinib, a Btk inhibitor that promotes mobilization of leukemic cells from SLOs, normalizes the imbalance between CXCR4/CCR7 and S1P1. Taken together, our results highlight the relevance of chemokine and S1P receptor recycling in CLL pathogenesis and clinical outcome. PMID- 26282176 TI - Noncultured epidermal-melanocyte cell suspension and dermal-fat grafting for the reconstruction of an irregular, atrophic, and depigmented forehead scar: an innovative approach. AB - Scars on the face 'eclipse' patient social life and provide challenge for the treating surgeon. 'Forehead' is difficult area on face to re-construct because of the inelastic, relatively immobile skin and subcutaneous tissue. The surgical correction of scar depends upon the site, size, type of scar and general condition of the patient. We describe an innovative approach to treat a depressed, de-pigmented, irregular scar placed vertically in the centre of forehead, in a young girl.. PMID- 26282175 TI - Ligand-Independent EGFR Signaling. AB - Constitutive activation of the EGFR is common in cancer due to EGFR wild-type (EGFRwt) overexpression or the presence of mutant EGFR. Signaling by constitutively active NSCLC EGFR mutants or the EGFRvIII mutant in glioblastoma has been studied intensively and the downstream signals are known. Normally, the EGFRwt is activated when it is exposed to ligand, resulting in activation of canonical signals such as ERK and Akt. The EGFRwt also becomes tyrosine phosphorylated and constitutively activated without ligand when it is overexpressed, but downstream signals are unclear. Recent studies have identified a noncanonical form of signaling triggered by EGFRwt exclusively in the absence of ligand that does not involve ERK or Akt activation but, instead, results in activation of the transcription factor IRF3. The addition of ligand turns off IRF3-dependent transcription and activates ERK and Akt. Thus, the EGFR triggers distinct and mutually exclusive signaling networks, depending on the presence of ligand. Furthermore, noncanonical EGFRwt signaling may influence response to treatment in cancer. Also, there are reports of both synergistic and antagonistic interactions between ligand-dependent EGFRwt and EGFRvIII signaling. Here, we discuss ligand-independent EGFR signal transduction by oncogenic EGFR mutants and EGFRwt, and review the interplay between EGFRwt and EGFRvIII. PMID- 26282178 TI - Understanding patient beliefs regarding the use of imaging in the management of low back pain. AB - BACKGROUND: Imaging for low back pain (LBP) remains common despite guidelines recommending against routine imaging. Patient beliefs about imaging may contribute to the problem. This study aimed to quantitatively investigate patient beliefs regarding the need for imaging in managing LBP and to investigate whether personal characteristics, pain characteristics or back pain beliefs are associated with imaging beliefs. METHODS: A survey was performed of consecutive patients presenting to general medical practitioners in Sydney, Australia. Nine medical clinics were selected across varied socioeconomic regions. Survey questions assessed beliefs about the importance of imaging for LBP, collected demographic information, LBP history and general beliefs about back pain. Descriptive statistics and multivariate logistic regression were used to analyse findings. RESULTS: Three hundred completed surveys were collected with a 79.6% response rate. The mean age was 44 years and 60.7% of respondents were women. Exactly, 54.3% (95% CI: 48.7-58.9%) believed that imaging was necessary for the best medical care for LBP. Exactly, 48.0% (95% CI: 42.4-53.6%) believed that everyone with LBP should obtain imaging. Increased age, lower education level, non-European or non-Anglo-saxon cultural background, history of previous imaging and Back Beliefs Questionnaire scores were associated with beliefs that imaging was necessary. CONCLUSION: Approximately, half of all patients presenting to a medical doctor consider low back imaging to be necessary. This may have important implications for overutilization of low back imaging investigations. Knowledge of the factors associated with the patient's belief that imaging is necessary may be helpful in designing appropriate interventions to reduce unnecessary imaging for LBP. PMID- 26282177 TI - Adherence to Medication Regimens is an Effective Indicator of Cognitive Dysfunction in Elderly Individuals. AB - BACKGROUND: Cognitive abilities strongly influence medication adherence among elderly individuals. We aimed to evaluate the relationship between medication adherence and cognitive decline using Lawton's instrumental activities of daily living (IADL) scoring system and the Mini-Mental State Examination (MMSE). METHODS: Receiver-operating characteristic (ROC) curves were used to evaluate the IADL scores and MMSE results. RESULTS: The ROC curve analysis of the IADL and MMSE results revealed that the shopping (MMSE cutoff = 22 points, sensitivity = 0.726, and specificity = 0.683) and responsibility for own medications (MMSE cutoff = 22 points, sensitivity = 0.759, and specificity = 0.720) categories were associated with declining IADL scores during early stage cognitive dysfunction. CONCLUSION: Declining IADL scores in the shopping and responsibility for own medications categories may be effective indices for predicting early-stage cognitive dysfunction in elderly individuals. Cognitive dysfunction screening at pharmacy counters may be useful. PMID- 26282179 TI - Synthesis and In Vitro Evaluation of a Photosensitizer-BODIPY Derivative for Potential Photodynamic Therapy Applications. AB - A new photosensitizer (1) based on the 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) scaffold has been synthesized. 1 is water soluble and showed an intense absorption band at 490 nm (E=77,600 cm(-1) m(-1)) and an emission at 514 nm. In vitro toxicity of 1 in the presence of light and in darkness has been studied with HeLa, HaCaT, MCF-7, and SCC-13 cell lines. Moreover, internalization studies of 1 in these cell lines were also performed. These results suggested that 1 is more toxic for SCC-13 and HeLa carcinoma cells than for the HaCaT non-cancerous immortal human keratinocytes. Toxicity upon light irradiation was due to the formation of singlet oxygen and reactive oxygen species (ROS). Cellular co localization experiments revealed preferential localization of the dye in the endoplasmic reticulum. PMID- 26282180 TI - Morbidity and medication in a large population of individuals with Down syndrome compared to the general population. AB - AIM: The aim of this study was to describe the incidence of morbidities and the prevalence of medical prescriptions in a large Down syndrome population. METHOD: A retrospective cohort study was carried out using the UK Clinical Practice Research Datalink from 1 January 2004 to 31 December 2013. We matched individuals with Down syndrome to randomly selected control participants by practice site, sex, birth year, and recording period. RESULTS: A total of 6430 individuals with Down syndrome (3009 females, 3421 males) and 19 176 controls (8966 females, 10,210 males) were included in the study. The incidence of cardiovascular disorders, gastrointestinal diseases (incidence rate ratio [IRR] 7.9 at 3 to <6y: yearly prevalence ratio [YPR] for laxatives 4.7), and sleeping disorders (IRR 4.8 in 3 to <6y) was increased in children with Down syndrome versus control participants. New onset of congenital heart malformation, ear diseases, eye disorders, autism, hypothyroidism, diabetes, and obesity were more frequent in childhood and remained elevated in adulthood (overall IRR 35.5, 1.7, 3.1, 4.4, 13.1, 1.3, and 2.6 respectively), whereas the gap widened in adulthood for epilepsy and intellectual disability (IRR 15.2 and 158 respectively, in participants older than 30y). At >= 30 years, the incidence of hypotension and dementia was raised (IRR 3.0 and 92.1 respectively; YPR for dementia drugs: 76.3); and that of hypertension, depression and anxiety was lowered (IRR 0.2, 0.5, and 0.4 respectively). INTERPRETATION: The profile of newly occurring morbidities in Down syndrome varies across the developmental lifespan. PMID- 26282182 TI - Arts as a vehicle for community building and post-disaster development. AB - Use of the arts in international aid is common in an ad hoc form, but it has not been systematically theorised or evaluated. The arts have the potential to be a culturally contextualised and sustainable intervention for adults and children in the aftermath of war or disaster. On the micro level, the arts are a method to enable the retrieval and reprocessing of traumatic memories that are often encoded in images rather than in words. On a macro level, they can help to reconstruct a group narrative of a disaster as well as mobilise people back into control of their lives. This paper researches a long-term project using arts in Sri Lanka following the civil war and tsunami. A central finding is the need to understand arts within their cultural context, and their usefulness in strengthening the voices and problem-solving capacities of the victims of the disaster. PMID- 26282183 TI - Lymphomatoid papulosis associated with follicular B-cell lymphoma in lymph nodes. PMID- 26282181 TI - p53 modulates the activity of the GLI1 oncogene through interactions with the shared coactivator TAF9. AB - The GLI1 oncogene and p53 tumor suppressor gene function in an inhibitory loop that controls stem cell and tumor cell numbers. Since GLI1 and p53 both interact with the coactivator TATA Binding Protein Associated Factor 9 (TAF9), we hypothesized that competition between these transcription factors for TAF9 in cancer cells may contribute to the inhibitory loop and directly affect GLI1 function and cellular phenotype. We showed that TAF9 interacts with the oncogenic GLI family members GLI1 and GLI2 but not GLI3 in cell-free pull-down assays and with GLI1 in rhabdomyosarcoma and osteosarcoma cell lines. Removal of the TAF9 binding acidic alpha helical transactivation domain of GLI1 produced a significant reduction in the ability of GLI1 to transform cells. We then introduced a point mutation into GLI1 (L1052I) that eliminates TAF9 binding and a point mutation into GLI3 (I1510L) that establishes binding. Wild-type and mutant GLI proteins that bind TAF9 showed enhanced transactivating and cell transforming activity compared with those that did not. Therefore, GLI-TAF9 binding appears important for oncogenic activity. We then determined whether wild-type p53 down regulates GLI function by sequestering TAF9. We showed that p53 binds TAF9 with greater affinity than does GLI1 and that co-expression of p53 with GLI1 or GLI2 down-regulated GLI-induced transactivation, which could be abrogated using mutant forms of GLI1 or p53. This suggests that p53 sequesters TAF9 from GLI1, which may contribute to inhibition of GLI1 activity by p53 and potentially impact therapeutic success of agents targeting GLI-TAF9 interactions in cancer. PMID- 26282184 TI - Matrix metalloproteases inhibition and biocompatibility of gold and platinum nanoparticles. AB - Matrix metalloprotease (MMP) inhibitors improve the longevity of dental adhesives/tooth bonds; however, biocompatibility is required for their clinical use. This study evaluated the inhibition of MMPs and toxicity of two gold (AuNPs) and platinum nanoparticles (PtNPs) as possible compounds for use in dental adhesives. The MMP assay for studying the interaction of MMPs and nanoparticles (NPs) was evaluated by an MMP assay kit and gelatin zymography. Cultured L929 fibroblast cells or RAW264 macrophages were exposed to NPs. The cellular responses to NPs were examined using cytotoxic (cell viability) and genotoxic assays (comet assay), and transmission electron microscopic (TEM) analysis. The mechanical properties (elastic modulus) of the experimental resin loaded with NPs were examined using thermomechanical analysis. All NPs inhibited MMP activity at relatively low concentrations. The NPs inhibit MMPs by chelating with the Zn(2+) bound in the active sites of MMPs. No cytotoxic and genotoxic effects were found in AuNPs, whereas the PtNPs possessed both adverse effects. In TEM analysis, the NPs were localized mainly in lysosomes without penetration into nuclei. The mechanical properties of the resins increased when AuNPs were added in resins, but not by PtNPs. AuNPs are attractive candidates to inhibit MMPs and improve the mechanical properties of resins without cytotoxic/genotoxic effects to cells, and therefore should be suitable for applications in adhesive resin systems. PMID- 26282185 TI - Identifying health outcomes in healthcare databases. AB - PURPOSE: The purpose of this review is to assist researchers in developing, using, and interpreting case-identifying algorithms in electronic healthcare databases. METHODS: We review clinical characteristics of health outcomes, data settings and informatics, and epidemiologic and statistical methods aspects as they pertain to the development and use of case-identifying algorithms. RESULTS: We offer a framework for thinking critically about the use of electronic health insurance data and electronic health records to identify the occurrence of health outcomes. Accuracy of case ascertainment in database research depends on many factors, including clinical and behavioral aspects of the health outcome, and details of database construction as it pertains to completeness and reliability of database content. Existing methods for diagnostic and screening tests, misclassification, validation studies, and predictive modelling can be usefully applied to improve case ascertainment in database research. CONCLUSIONS: Good case-identifying algorithms are based on a sound understanding of care-seeking behavior and patterns of clinical diagnosis and treatment in the study population and details about the construction and characteristics of the database. Researchers should use quantitative bias analyses to take into account the performance characteristics of case-identifying algorithms and their impact on study results. PMID- 26282187 TI - Plasmonic Gold Decorated MWCNT Nanocomposite for Localized Plasmon Resonance Sensing. AB - The synergism of excellent properties of carbon nanotubes and gold nanoparticles is used in this work for bio-sensing of recombinant bovine growth hormones (rbST) by making Multi Wall Carbon Nanotubes (MWCNT) locally optically responsive by augmenting it optical properties through Localized Surface Plasmon Resonance (LSPR). To this purpose, locally gold nano particles decorated gold-MWCNT composite was synthesized from a suspension of MWCNT bundles and hydrogen chloroauric acid in an aqueous solution, activated ultrasonically and, then, drop casted on a glass substrate. The slow drying of the drop produces a "coffee ring" pattern that is found to contain gold-MWCNT nanocomposites, accumulated mostly along the perimeter of the ring. The reaction is studied also at low-temperature, in the vacuum chamber of the Scanning Electron Microscope and is accounted for by the local melting processes that facilitate the contact between the bundle of tubes and the gold ions. Biosensing applications of the gold-MWCNT nanocomposite using their LSPR properties are demonstrated for the plasmonic detection of traces of bovine growth hormone. The sensitivity of the hybrid platform which is found to be 1 ng/ml is much better than that measuring with gold nanoparticles alone which is only 25 ng/ml. PMID- 26282186 TI - Haematological rather than skeletal muscle adaptations contribute to the increase in peak oxygen uptake induced by moderate endurance training. AB - It remains unclear whether improvements in peak oxygen uptake (V(O2peak)) following endurance training (ET) are primarily determined by central and/or peripheral adaptations. Herein, we tested the hypothesis that the improvement in V(O2peak) following 6 weeks of ET is mainly determined by haematological rather than skeletal muscle adaptations. Sixteen untrained healthy male volunteers (age = 25 +/- 4 years, V(O2peak) = 3.5 +/- 0.5 l min(-1)) underwent supervised ET (6 weeks, 3-4 sessions per week). V(O2peak), peak cardiac output (Q(peak)), haemoglobin mass (Hb(mass)) and blood volumes were assessed prior to and following ET. Skeletal muscle biopsies were analysed for mitochondrial volume density (Mito(VD)), capillarity, fibre types and respiratory capacity (OXPHOS). After the post-ET assessment, red blood cell volume (RBCV) was re-established at the pre-ET level by phlebotomy and V(O2peak) and Q(peak) were measured again. We speculated that the contribution of skeletal muscle adaptations to the ET-induced increase in V(O2peak) would be revealed when controlling for haematological adaptations. V(O2peak) and Q(peak) were increased (P < 0.05) following ET (9 +/- 8 and 7 +/- 6%, respectively) and decreased (P < 0.05) after phlebotomy (-7 +/- 7 and -10 +/- 7%). RBCV, plasma volume and Hb(mass) all increased (P < 0.05) after ET (8 +/- 4, 4 +/- 6 and 6 +/- 5%). As for skeletal muscle adaptations, capillary to-fibre ratio and total Mito(VD) increased (P < 0.05) following ET (18 +/- 16 and 43 +/- 30%), but OXPHOS remained unaltered. Through stepwise multiple regression analysis, Q(peak), RBCV and Hb(mass) were found to be independent predictors of V(O2peak). In conclusion, the improvement in V(O2peak) following 6 weeks of ET is primarily attributed to increases in Q(peak) and oxygen-carrying capacity of blood in untrained healthy young subjects. PMID- 26282188 TI - CFTR genotype-related body water and electrolyte balance during a marathon. AB - The aim of this investigation was to determine the influence of CFTR genotype on body water and electrolyte balance during a marathon. Fifty-one experienced runners completed a marathon race. Before and after the race, body mass and a sample of venous blood were obtained. During the race, sweat samples were collected using sweat patches, and fluid and electrolyte intake were obtained using self-reported questionnaires. Thirty-eight participants (74.5% of the total) were 7T/7T homozygotes, 11 (21.6%) were 7T/9T heterozygotes, and one participant presented the rare genotype 5T/7T. Another participant with 9T/9T presented the mutation p.L206W. Participants with 7T/7T showed higher sweat sodium concentrations (42.2 +/- 21.6 mmol/L) than 7T/9T (29.0 +/- 24.7 mmol/L; P = 0.04). The runner with the 5T/7T genotype (10.2 mmol/L) and the participant with the p.L206W mutation (20.5 mmol/L) exhibited low-range sweat sodium concentrations. However, post-race serum sodium concentration was similar in 7T/7T and 7T/9T (142.1 +/- 1.3 and 142.4 +/- 1.6 mmol/L, respectively; P = 0.27) and did not show abnormalities in participants with the 5T/7T genotype (140.0 mmol/L) and the p.L206W mutation (143.0 mmol/L). Runners with the CFTR-7T/7T genotype exhibited increased sweat sodium concentrations during a marathon. However, this phenotype was not related with increased likelihood of suffering body water and electrolyte imbalances during real competitions. PMID- 26282189 TI - Assessing Technology in the Absence of Proof: Trust Based on the Interplay of Others' Opinions and the Interaction Process. AB - OBJECTIVE: The present research addresses the question of how trust in systems is formed when unequivocal information about system accuracy and reliability is absent, and focuses on the interaction of indirect information (others' evaluations) and direct (experiential) information stemming from the interaction process. BACKGROUND: Trust in decision-supporting technology, such as route planners, is important for satisfactory user interactions. Little is known, however, about trust formation in the absence of outcome feedback, that is, when users have not yet had opportunity to verify actual outcomes. METHOD: Three experiments manipulated others' evaluations ("endorsement cues") and various forms of experience-based information ("process feedback") in interactions with a route planner and measured resulting trust using rating scales and credits staked on the outcome. Subsequently, an overall analysis was conducted. RESULTS: Study 1 showed that effectiveness of endorsement cues on trust is moderated by mere process feedback. In Study 2, consistent (i.e., nonrandom) process feedback overruled the effect of endorsement cues on trust, whereas inconsistent process feedback did not. Study 3 showed that although the effects of consistent and inconsistent process feedback largely remained regardless of face validity, high face validity in process feedback caused higher trust than those with low face validity. An overall analysis confirmed these findings. CONCLUSION: Experiential information impacts trust even if outcome feedback is not available, and, moreover, overrules indirect trust cues-depending on the nature of the former. APPLICATION: Designing systems so that they allow novice users to make inferences about their inner workings may foster initial trust. PMID- 26282190 TI - The Effects of Age, Gender, and Hand on Force Control Capabilities of Healthy Adults. AB - OBJECTIVE: The present study examined the effects of age (20s to 70s), gender (male and female), and hand (dominant and nondominant) on force control capabilities (FCCs) in four force control phases (initiation, development, maintenance, and termination). BACKGROUND: Normative data of FCCs by force control phase are needed for various populations in age and gender to identify a type of motor performance reduction and its severity. METHOD: FCCs of 360 participants (30 for each combination of age group and gender) were measured using a finger dynamometer and quantified in terms of initiation time (IT), development time (DT), maintenance error (ME), and termination time (TT). RESULTS: Although gradual increases (1%~28%) by age were shown in IT, DT, and TT, a dramatic increase in ME was observed among participants in their 50s (26%), 60s (68%), and 70s (160%) compared to those in their 20s~40s. The most distinctive interaction effect of age and gender was found in ME out of the four FCC measures. Lastly, hand and its related interactions were not found significant. CONCLUSION: Normative FCC data were established for four age groups (20s~40s, 50s, 60s, and 70s) and gender. APPLICATION: The normative FCC data can be used for evaluating an individual's motor performance, screening patients with brain disorders, and designing input devices triggered and/or operated by the finger. PMID- 26282191 TI - Detect Long-term Complications After ICD Replacement (DECODE): Rationale and Study Design of a Multicenter Italian Registry. AB - The replacement of implantable cardioverter-defibrillators (ICDs) may give rise to considerable clinical consequences, the importance of which is underrated by the medical community. Replacement-related adverse events are difficult to identify and require monitoring of both short-term complications and long-term patient outcome. The aim of this study is to perform a structured evaluation of both short- and long-term adverse events and a cost analysis of consecutive ICD replacement procedures. Detect Long-term Complications After ICD Replacement (DECODE) is a prospective, single-arm, multicenter cohort study designed to estimate long-term complication rates (at 12 months and 5 years) in patients undergoing ICD generator replacement. The study will also evaluate predictors of complications, patient management before and during the replacement procedure in clinical practice, and the costs related to use of health care resources. About 800 consecutive patients with standard indications for ICD generator replacement will be enrolled in this study. The decision to undertake generator replacement/upgrade will be made according to the investigators' own judgment (which will be recorded). Patients will be followed for 60 months through periodic in-hospital examinations or remote monitoring. Detailed data on complications related to ICD replacement in current clinical practice are still lacking. The analysis of adverse events will reveal the value of new preventive strategies, thereby yielding both clinical and economic benefits. Moreover, assessment of complication rates after ICD replacement in a real-life setting will help estimate the actual long-term cost of ICD therapy and assess the real impact of increasing ICD longevity on cost-effectiveness. PMID- 26282192 TI - Talking to pregnant women about stillbirth: Evaluating the effectiveness of an information workshop for midwives using pre and post intervention surveys. AB - OBJECTIVE: The project aimed to establish the level of knowledge a group of midwives had about risk factors for stillbirth and identify their current willingness to raise and discuss stillbirth with pregnant women during standard antenatal care. DESIGN: Surveys were administered pre and post an education intervention. The intervention consisted of a half day education workshop. A change in knowledge pre and post intervention was measured as a means to determine the effectiveness of the workshop. SETTINGS: The workshop first provided participants with up-to-date information about modifiable and preventative risk factors for stillbirth and then provided them with the opportunity to practice a range of strategies to assist them to becoming confident in raising and discussing the topic of stillbirth. PARTICIPANTS: Three workshops were offered and a total of 109 qualified midwives attended. METHODS: In order to explore the level of knowledge increase and retention of knowledge about stillbirth as well as participants willingness to discuss stillbirth with pregnant women, comparisons were made between the pre workshop survey responses and those given to the two follow-up surveys immediately following and 3 months after the workshop. RESULTS: There was a statistically significant improvement in knowledge about stillbirth as well as in participant willingness to engage the pregnant women in their care in a conversation about stillbirth. KEY CONCLUSIONS: Providing a workshop on stillbirth for registered midwives is quite effective in raising their awareness about stillbirth. However, before substantial changes can be made in stillbirth awareness, ways and means to sensitively promote public awareness of stillbirth need to be explored and anxieties and taboos addressed. Research could explore whether or not a stillbirth awareness message actually does make women anxious, and if so the nature of this anxiety and how this anxiety might best be ameliorated. PMID- 26282193 TI - Beginning and advanced students' perceptions of the use of low- and high-fidelity mannequins in nursing simulation. AB - BACKGROUND: There is little research evidence that demonstrates the difference between the use of low- and high-fidelity mannequins in assisting students to acquire their skills when students are at different points in their nursing education experience. OBJECTIVES: Our study examined differences between the use of low- and high-fidelity mannequins on student outcomes with both beginner and advanced students. DESIGN: A quasi-experimental investigation. SETTINGS: Participants performed two simulations, one simulation using a low-fidelity mannequin and the other simulation using a high-fidelity mannequin. PARTICIPANTS: First and fourth semester pre-licensure students from a Bachelor of Science in Nursing program and an accelerated nursing entry program participated in this study. METHODS: A Students' Satisfaction and Self-confidence Scale and Simulation Design Scale were used to obtain data. Statistical analysis was performed using the Statistical Package for the Social Sciences for Windows version 17.0. The results obtained from scales were compared using Wilcoxon sign test and Mann Whitney U test. A p value of <0.05 was considered statistically significant. RESULTS: The student satisfaction score of the students in the low-fidelity mannequin group was 3.62+/-1.01, while that of the students in the high-fidelity mannequin group was 4.67+/-0.44'dir (p=0.01). The total score of the simulation design scale in the low-fidelity mannequin group was 4.15+/-0.63, while it was 4.73+/-0.33 in the high-fidelity mannequin group (p=0.01). CONCLUSIONS: Students' perceptions of simulation experiences using high-fidelity mannequins were found to be higher in contrast to their perceptions of experiences using low-fidelity mannequins. PMID- 26282194 TI - Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia. AB - BACKGROUND: Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate host defence against infections, which remains a cause of morbidity and death. Suppression commonly occurs in the first days after cessation of glucocorticoid therapy, but the exact duration is unclear. This review is an update of a previously published Cochrane review. OBJECTIVES: To examine the occurrence and duration of HPA axis suppression after (each cycle of) glucocorticoid therapy for childhood ALL. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 6, 2014), MEDLINE/PubMed (from 1945 to June 2014), and EMBASE/Ovid (from 1980 to June 2014). In addition, we searched reference lists of relevant articles, conference proceedings (the International Society for Paediatric Oncology and the American Society of Clinical Oncology from 2005 to 2013), and ongoing trial databases (the ISRCTN register and the NIH register via http://www.controlled-trials.com in June 2014). SELECTION CRITERIA: All study designs, except case reports and patient series with fewer than 10 children, examining the effect of glucocorticoid therapy for childhood ALL on the HPA axis function. DATA COLLECTION AND ANALYSIS: Two review authors independently performed the study selection. One review author performed the data extraction and 'Risk of bias' assessment, which another review author checked. MAIN RESULTS: We identified eight studies (total of 218 children), including two randomised controlled trials (RCTs), that assessed the adrenal function. None of the studies assessed the HPA axis at the level of the hypothalamus, pituitary, or both. Due to substantial differences between studies, we could not pool results. All of the studies had some methodological limitations. The included studies demonstrated that adrenal insufficiency occurs in nearly all children in the first days after cessation of glucocorticoid treatment for childhood ALL. The majority of children recovered within a few weeks, but a small number of children had ongoing adrenal insufficiency lasting up to 34 weeks. In the RCTs, the occurrence and duration of adrenal insufficiency did not differ between the prednisone and dexamethasone arms. In one study, it appeared that treatment with fluconazole prolonged the duration of adrenal insufficiency. Furthermore, one of the studies evaluated the presence of infections or stress episodes, or both as a risk factor for adrenal insufficiency. The authors found no relationship between the presence of infection/stress and adrenal insufficiency. AUTHORS' CONCLUSIONS: We concluded that adrenal insufficiency commonly occurs in the first days after cessation of glucocorticoid therapy for childhood ALL, but the exact duration is unclear. Since no data on the level of the hypothalamus and the pituitary were available, we cannot make any conclusions regarding those outcomes. Clinicians should consider prescribing glucocorticoid replacement therapy during periods of serious stress in the first weeks after cessation of glucocorticoid therapy for childhood ALL to reduce the risk of life-threatening complications. However, more high quality research is needed for evidence-based guidelines for glucocorticoid replacement therapy.Special attention should be paid to patients receiving fluconazole therapy, and perhaps similar antifungal drugs, as this may prolong the duration of adrenal insufficiency.Finally, it would be relevant to further investigate the relationship between present infection/stress and adrenal insufficiency in a larger, separate study specially designed for this purpose. PMID- 26282195 TI - Small animal cardiovascular MR imaging and spectroscopy. AB - The use of MR imaging and spectroscopy for studying cardiovascular disease processes in small animals has increased tremendously over the past decade. This is the result of the remarkable advances in MR technologies and the increased availability of genetically modified mice. MR techniques provide a window on the entire timeline of cardiovascular disease development, ranging from subtle early changes in myocardial metabolism that often mark disease onset to severe myocardial dysfunction associated with end-stage heart failure. MR imaging and spectroscopy techniques play an important role in basic cardiovascular research and in cardiovascular disease diagnosis and therapy follow-up. This is due to the broad range of functional, structural and metabolic parameters that can be quantified by MR under in vivo conditions non-invasively. This review describes the spectrum of MR techniques that are employed in small animal cardiovascular disease research and how the technological challenges resulting from the small dimensions of heart and blood vessels as well as high heart and respiratory rates, particularly in mice, are tackled. PMID- 26282196 TI - Solid-state NMR methods for oriented membrane proteins. AB - Oriented-sample solid-state NMR represents one of few experimental methods capable of characterising the membrane-bound conformation of proteins in the cell membrane. Since the technique was developed 25 years ago, the technique has been applied to study the structure of helix bundle membrane proteins and antimicrobial peptides, characterise protein-lipid interactions, and derive information on dynamics of the membrane anchoring of membrane proteins. We will review the major developments in various aspects of oriented-sample solid-state NMR, including sample-preparation methods, pulse sequences, theory required to interpret the experiments, perspectives for and guidelines to new experiments, and a number of representative applications. PMID- 26282198 TI - Theoretical tools for the design of NMR relaxation dispersion pulse sequences. AB - Recent decades have witnessed tremendous progress in the development of new experimental methods for studying biomolecules, particularly in the field of NMR relaxation dispersion. Here we review the theoretical frameworks that provided the insights necessary for such progress. The effect of radio-frequency manipulations on spin systems is discussed using Average Hamiltonian Theory (AHT), Average Liouvillian Theory (ALT), and Bloch-Wangsness-Redfield (BWR) relaxation theory. We illustrate these concepts using the case of Heteronuclear Double Resonance (HDR) methods. PMID- 26282199 TI - Fenofibrate activates Nrf2 through p62-dependent Keap1 degradation. AB - Peroxisome proliferator-activated receptor alpha (PPARalpha) activates the beta oxidation of fatty acids in the liver. Fenofibrate is a potent agonist of PPARalpha and is used in the treatment of hyperlipidemia. Fenofibrate treatment often induces the production of intracellular reactive oxygen species (ROS), leading to cell death. The nuclear factor erythroid 2-related factor 2 (Nrf2) Kelch-like ECH-associated protein 1 (Keap1) pathway is an essential component of the defense mechanism against oxidative stress. However, the molecular mechanism underlying the regulation of the Nrf2-Keap1 pathway in fenofibrate-induced cell death is not known. In this study, we demonstrated that fenofibrate induces Keap1 degradation and Nrf2 activation. This fenofibrate-mediated Keap1 degradation is partly dependent on autophagy. Furthermore, fenofibrate-induced Keap1 degradation followed by Nrf2 activation is mainly mediated by p62, which functions as an adaptor protein in the autophagic pathway. Consistent with these findings, ablation of p62 increased fenofibrate-mediated apoptotic cell death associated with ROS accumulation. These results strongly suggest that p62 plays a crucial role in preventing fenofibrate-induced cell death. PMID- 26282200 TI - Different roles of GPR120 and GPR40 in the acquisition of malignant properties in pancreatic cancer cells. AB - Free fatty acids (FFAs) act as extracellular signaling molecules through binding to G-protein-coupled FFA receptors (FFARs). GPR120 and GPR40 are identified as FFARs for medium- and long-chain fatty acids. In the present study, we investigated roles of GPR120 and GPR40 in cellular functions of pancreatic cancer PANC-1 cells, using GPR120 and GPR40 knockdown cells (PANC-sh120 and PANC-sh40 cells respectively). In cell motility assay, PANC-sh120 cells showed the low cell motility, compared with control cells. In contrast, the cell motility of PANC sh40 cells was significantly higher than that of control cells. Activity levels of matrix metalloproteinases (MMPs) were measured by gelatin zymography. While PANC-sh120 cells indicated the reduced MMP-2 activity, MMP-2 activity in PANC sh40 cells was significantly higher than that in control cells. On the other hand, no activation of MMP-9 was detected in all cells. In colony assay, the large sized colonies were markedly formed in PANC-sh40 cells. No colony formation was observed in PANC-sh120 cells as well as control cells. These results suggest that distinct effects of GPR120 and GPR40 are involved in the acquisition of malignant property in pancreatic cancer cells. PMID- 26282201 TI - A network-based approach to identify disease-associated gene modules through integrating DNA methylation and gene expression. AB - Formation and progression of complex diseases are generally the joint effect of genetic and epigenetic disorders, thus an integrative analysis of epigenetic and genetic data is essential for understanding mechanism of the diseases. In this study, we integrate Illuminate 450k DNA methylation and gene expression data to calculate the weights of gene network using Principal Component Analysis (PCA) and Canonical Correlation Analysis (CCA). The approach considers all methylation values of CpG sites in a gene, rather than averaging them which was used in other studies ignoring the variability of the methylation sites. Through comparing topological features of control network with those of case network, including global and local features, candidate disease-associated genes and gene modules are identified. We apply the approach to real data, breast invasive carcinoma (BRCA). It successfully identifies susceptibility breast cancer-related genes, such as TP53, BRCA1, EP300, CDK2, MCM7 and so forth, within which most are previously known to breast cancer. Also, GO and pathway enrichment analysis indicate that these genes enrich in cell apoptosis and regulation of cell death which are cancer-related biological processes. Importantly, through analyzing the functions and comparing expression and methylation values of these genes between cases and controls, we find some genes, such as VASN, SNRPD3, and gene modules, targeted by POLR2C, CHMP1B and TAF9, which might be novel breast cancer-related biomarkers. PMID- 26282197 TI - Mechanisms of amyloid formation revealed by solution NMR. AB - Amyloid fibrils are proteinaceous elongated aggregates involved in more than fifty human diseases. Recent advances in electron microscopy and solid state NMR have allowed the characterization of fibril structures to different extents of refinement. However, structural details about the mechanism of fibril formation remain relatively poorly defined. This is mainly due to the complex, heterogeneous and transient nature of the species responsible for assembly; properties that make them difficult to detect and characterize in structural detail using biophysical techniques. The ability of solution NMR spectroscopy to investigate exchange between multiple protein states, to characterize transient and low-population species, and to study high molecular weight assemblies, render NMR an invaluable technique for studies of amyloid assembly. In this article we review state-of-the-art solution NMR methods for investigations of: (a) protein dynamics that lead to the formation of aggregation-prone species; (b) amyloidogenic intrinsically disordered proteins; and (c) protein-protein interactions on pathway to fibril formation. Together, these topics highlight the power and potential of NMR to provide atomic level information about the molecular mechanisms of one of the most fascinating problems in structural biology. PMID- 26282202 TI - Overexpression of porcine lipoprotein-associated phospholipase A2 in swine. AB - Lipoprotein-associated phospholipase A 2 (Lp-PLA2) is associated with the risk of vascular disease. It circulates in human blood predominantly in association with low-density lipoprotein cholesterol (LDL-C) and hydrolyses oxidized phospholipids into pro-inflammatory products. However, in the mouse circulation, it predominantly binds to high-density lipoprotein cholesterol (HDL-C) and exhibits anti-inflammatory properties. To further investigate the effects of Lp-PLA2 in the circulation, we generated over-expressed Lp-PLA2 transgenic swine. The eukaryotic expression plasmid of porcine Lp-PLA2 which driven by EF1alpha promoter was constructed and generate transgenic swine via SCNT. The expression and activity of Lp-PLA2 in transgenic swine were evaluated, and the total cholesterol (TC), HDL-C, LDL-C and triglyceride (TG) levels in the fasting and fed states were also assessed. Compared with wild-type swine controls, the transgenic swine exhibited elevated Lp-PLA2 mRNA levels and activities, and the activity did not depend on the feeding state. The TC, HDL-C and LDL-C levels were not significantly increased. There was no change in the TG levels in the fasting state between transgenic and control pigs. However, in the fed state, the TG levels of transgenic swine were slightly increased compared with the control pigs and were significantly elevated compared with the fasting state. In addition, inflammatory gene (interleukin [IL]-6, monocyte chemotactic protein [MCP]-1 and tumor necrosis factor [TNF]-alpha) mRNA levels in peripheral blood mononuclear cells (PBMCs) were significantly increased. The results demonstrated that Lp-PLA2 is associated with triglycerides which may be helpful for understanding the relationship of this protein with cardiovascular disease. PMID- 26282203 TI - A model for non-obligate oligomer formation in protein aggregration. AB - Using solvent-exposed intramolecular backbone hydrogen bonds as physico-chemical descriptors for protein packing, a role for transient, non-obligate oligomers in the formation of aberrant protein aggregates is presented. Oligomeric models of the both wild type (wt) and select mutant variants of superoxide dismutase (SOD1) are proposed to provide a structural basis for investigating the etiology of Amyotrophic Lateral Sclerosis (ALS). PMID- 26282204 TI - Human RNA polymerase II associated factor 1 complex promotes tumorigenesis by activating c-MYC transcription in non-small cell lung cancer. AB - Human RNA polymerase II (RNAPII)-associated factor 1 complex (hPAF1C) plays a crucial role in protein-coding gene transcription. Overexpression of hPAF1C has been implicated in the initiation and progression of various human cancers. However, the molecular pathways involved in tumorigenesis through hPAF1C remain to be elucidated. The current study suggested hPAF1C expression as a prognostic biomarker for early stage non-small cell lung cancer (NSCLC) and patients with low hPAF1C expression levels had significantly better overall survival. Furthermore, the expression of hPAF1C was found to be positively correlated with c-MYC expression in patient tumor samples and in cancer cell lines. Mechanistic studies indicated that hPAF1C could promote lung cancer cell proliferation through regulating c-MYC transcription. These results demonstrated the prognostic value of hPAF1C in early-stage NSCLC and the role of hPAF1C in the transcriptional regulation of c-MYC oncogene during NSCLC tumorigenesis. PMID- 26282205 TI - Inhibition of long-chain acyl-CoA synthetase 4 facilitates production of 5, 11 dihydroxyeicosatetraenoic acid via the cyclooxygenase-2 pathway. AB - Long chain acyl-CoA synthetases (ACSLs) are a family of enzymes that convert free long chain fatty acids into their acyl-CoA forms. Among ACSL enzymes, ACSL4 prefers arachidonic acid (AA) as a substrate and plays an important role in re esterification of free AA. We previously reported that the suppression of ACSL4 activity by treatment with an ACSL inhibitor or a small interfering RNA markedly enhanced interleukin-1beta (IL-1beta)-dependent prostaglandin (PG) biosynthesis in rat fibroblastic 3Y1 cells. We show here that in addition to these prostanoids, cytokine-dependent production of 5,11-dihydroxyeicosatetraenoic acid (5,11-diHETE), a cyclooxygenase product of 5-hydroxyeicosatetraenoic acid (5 HETE), was enhanced by the inhibition of ACSL4 activity. Treatment of several types of cells with an ACSL inhibitor, triacsin C, markedly enhanced IL-1beta dependent production of 5,11-diHETE. siRNA-mediated knockdown of ACSL4 also enhanced IL-1beta-dependent production of 5,11-diHETE from 3Y1 cells. The production of 5,11-diHETE was significantly decreased by a cyclooxygenase (COX)-2 selective inhibitor, NS-398, but not by a 5-lipoxygenase activating protein (FLAP) inhibitor, MK-886. The inhibition of ACSL enzymes significantly facilitated release of not only 5-HETE but also 8-HETE, 9-HETE, 11-HETE, 12-HETE, and 15-HETE, independently of IL-1beta stimulation. In vitro analysis showed that a recombinant COX-2 enzyme more effectively metabolized 5(S)-HETE to 5-11-diHETE compared to COX-1 enzyme. From these results, we proposed the following mechanism of 5,11-diHETE biosynthesis in these cells: 1) inhibition of ACSL4 causes accumulation of free AA; 2) the accumulated AA is nonspecifically converted into various HETEs; and 3) among these HETEs, 5-HETE is metabolized into 5,11-diHETE by cytokine-induced COX-2. PMID- 26282206 TI - Serum peptidome profiling analysis for the identification of potential biomarkers in cervical intraepithelial neoplasia patients. AB - Cervical intraepithelial neoplasia (CIN) is a precancerous disease of cervical squamous cell carcinoma. We Used Mass Spectrometry based peptidome profile study to predict the transformation of CIN1, which is the primary stage of this lesion. . Serum samples of 34 Cervical squamous cell carcinoma patients, 31 healthy controls, and 29 CIN1 samples were analyzed. Peptides were purified by WCX magnetic beads (Bioyong), and analyzed by MALDI TOF (Bruker). Raw data were analyzed by BioExplorer software (Bioyong). The results showed 14 mass peaks with significant differences. The diagnosis model is established by analyzing peptide profiles of 15 SCC patients and 20 healthy women serum, with a sensitivity of 100% and specificity of 100.00%. In validation set, the SCC diagnosis model also had good performance with a sensitivity of 80%, a specificity of 100%. In addition, this model could predict 29 CIN1 patients with accuracy of 55.17%. These results would provide a new method to predict the trend of CIN1 and take effective measures for high risk group timely. PMID- 26282207 TI - The E-box-like sterol regulatory element mediates the insulin-stimulated expression of hepatic clusterin. AB - Clusterin (also known as apolipoprotein J) is a highly conserved glycoprotein involved in various biological processes, including attenuation of complement activity, sperm maturation, apoptosis, and reverse lipid transport. Although clusterin is reportedly associated with metabolic diseases, the metabolic regulation of clusterin expression is largely unknown. We investigated the effect of insulin on hepatic clusterin expression and its underlying mechanisms. Insulin increased the mRNA and protein levels of clusterin in primary hepatocytes and hepatoma cell lines. Serial deletion and mutant analysis of the clusterin promoter demonstrated that insulin-stimulated transactivation is mediated via a non-canonical E-box (NCE-box) motif in the proximal upstream region. Interestingly, sterol regulatory element binding protein-1c (SREBP-1c) co transfection showed the same transactivation pattern as insulin stimulation in serial deletion and mutant promoter analysis. In contrast, co-transfection with a dominant negative form of SREBP-1c inhibited insulin-stimulated clusterin expression. Furthermore, insulin increased the recruitment of SREBP-1c to the NCE box of the clusterin promoter region. Taken together, our results suggest that an NCE-box within the clusterin promoter is necessary for insulin-stimulated hepatic expression of clusterin via SREBP-1c. PMID- 26282208 TI - Functional Analysis and Characterization of Differential Coexpression Networks. AB - Differential coexpression analysis is emerging as a complement to conventional differential gene expression analysis. The identified differential coexpression links can be assembled into a differential coexpression network (DCEN) in response to environmental stresses or genetic changes. Differential coexpression analyses have been successfully used to identify condition-specific modules; however, the structural properties and biological significance of general DCENs have not been well investigated. Here, we analyzed two independent Saccharomyces cerevisiae DCENs constructed from large-scale time-course gene expression profiles in response to different situations. Topological analyses show that DCENs are tree-like networks possessing scale-free characteristics, but not small world. Functional analyses indicate that differentially coexpressed gene pairs in DCEN tend to link different biological processes, achieving complementary or synergistic effects. Furthermore, the gene pairs lacking common transcription factors are sensitive to perturbation and hence lead to differential coexpression. Based on these observations, we integrated transcriptional regulatory information into DCEN and identified transcription factors that might cause differential coexpression by gain or loss of activation in response to different situations. Collectively, our results not only uncover the unique structural characteristics of DCEN but also provide new insights into interpretation of DCEN to reveal its biological significance and infer the underlying gene regulatory dynamics. PMID- 26282210 TI - Paediatrics: Guidelines for UTI and antenatal hydronephrosis should be gender specific. PMID- 26282211 TI - Incontinence: Preoperative urodynamics--self evident or evidently unnecessary? PMID- 26282212 TI - Prostate cancer: Novel xenografts in mice--a new wave of preclinical models. PMID- 26282213 TI - Infection: HipA and multidrug tolerance in urinary tract infection. PMID- 26282214 TI - [Radiotherapy in elderly patients, recommendations for the main localizations: Breast, prostate and gynaecological cancers]. AB - Modifications of radiotherapy indications or schedules because of age could be discussed in view of a different evolution of the disease or because of specific toxicities. One important aim is to decrease the number of hospital transports. For breast cancer, the rate of local relapse after lumpectomy is lower in old patients; moreover, characteristics of the disease are often more favourable (hormonosensitivity, low grade). However, adjuvant irradiation decreases significantly the incidence of breast relapse and must be systematically proposed. Hypofractionnated schedules must be recommended; limited data are available for accelerated partial breast irradiation in old women and these techniques must not be used in routine. For low or intermediate risk prostate cancer, assessment of comorbidities is crucial before considering any invasive treatment. A life expectancy of at least 10 years is required if a curative approach, potentially toxic is proposed. In this case, radiotherapy is often the good choice, giving less sequelae than surgery. The indication of androgen deprivation must take into account cardiovascular and bone history. Management of gynaecological cancers must follow the same recommendations as in young women. Exclusive postoperative brachytherapy must be recommended in early stage endometrial carcinomas. Brachytherapy must be also systematically integrated in the radiotherapy program for cervix cancers, even in old women. PMID- 26282215 TI - [Which constraints for which organs at risk in radiotherapy for adult patients?]. AB - The delineation of organs at risk is a part of the planning of irradiation treatments. With the delineation of the target volumes, this task is essential and is followed by the appropriate calculations of a dose distribution from radiation beams and the validation of the treatment plan. The contouring of organs at risk could influence the dosimetric parameters, treatment planning and also the outcome of the patient. The treatment intent (curative or palliative), doses and fractionations and also the type of organs at risk have an impact on the delineation. Optimized radiation techniques and reirradiations make delineation and definition of doses constraints more difficult. The second edition of the guidelines established by the French society of radiation oncologists (SFRO) includes a chapter dedicated to the delineation of organs at risk and dose constraints. The transposition of these recommendations in current practice remains the responsibility of the radiation oncologist who implements them and who has to judge their relevance. PMID- 26282216 TI - [Follow-up after radiation therapy for cervical cancer]. AB - Radiation therapy plays a central role in treatment strategies of cervical cancer. Follow-up after external pelvic radiation therapy and brachytherapy is based upon French and international specific recommendations. It aims to assess early tumour response, and to detect local or metastatic recurrences which can be suitable for salvage treatment. Follow-up after radiation therapy for cervical cancer should also assess gastro-intestinal, urinary and sexual toxicities which may have an impact on quality of life. This is a major concern in the evaluation of the results of intensity-modulated radiation therapy (IMRT) and MRI-guided brachytherapy, which should lead to a better local control and to a better bowel tolerance. PMID- 26282217 TI - MiR-661 contributed to cell proliferation of human ovarian cancer cells by repressing INPP5J expression. AB - Accumulating evidence has emerged important roles for microRNAs (miRNAs) participating in oncogenesis and growth of various cancers. We hypothesized that miR-661 played an important role in cell growth of ovarian cancer. Here, we found miR-661 was upregulated in human ovarian cancer cell lines and clinical tumor tissues. Our results revealed that miR-661 directly targeted INPP5J, thereby acting as tumor promoter in ovarian cancer cells by blocking cell proliferation. Importantly, we identified miR-661 as a positive regulator of INPP5J-induced AKT pathway. Taken together, our study sheds light onto the role of miR-661 as tumor promoter by targeting the INPP5J gene, and then promoting cell proliferation of ovarian cancer. PMID- 26282209 TI - Safety considerations for synthetic sling surgery. AB - Implantation of a synthetic midurethral sling (SMUS) is the most commonly performed anti-incontinence operation in women worldwide. The effectiveness of the SMUS is comparable to that of the historical gold standards--autologous fascial slings and the Burch colposuspension. Much controversy, however, has evolved regarding the safety of this type of sling. Overall, the quality of the studies with respect to assessing risks of SMUS-associated complications is currently poor. The most common risks in patients with SMUS include urethral obstruction requiring surgery (2.3% of patients with SMUS), vaginal, bladder and/or urethral erosion requiring surgery (1.8%) and refractory chronic pain (4.1%); these data likely represent the minimum risks. In addition, the failure rate of SMUS implantation surgery is probably at least 5% in patients with stress urinary incontinence (SUI). Furthermore, at least one-third of patients undergoing sling excision surgery develop recurrent SUI. Considering the additional risks of refractory overactive bladder, fistulas and bowel perforations, among others, the overall risk of a negative outcome after SMUS implantation surgery is >=15%. PMID- 26282218 TI - Schisandrin B shows neuroprotective effect in 6-OHDA-induced Parkinson's disease via inhibiting the negative modulation of miR-34a on Nrf2 pathway. AB - BACKGROUND: MiR-34 family members have been previously shown to play potential functional role in Parkinson's disease (PD) pathogenesis. However, the regulatory role of miR-34a has not been demonstrated in PD yet. This study aims to clarify the potential neuroprotective effect of Schisandrin B (Sch B) involving miR-34a function in 6-OHDA-induced PD model. METHODS: The expression changes of miR-34a and Nrf2 pathway related genes were detected in 6-OHDA-treated SH-SY5Y cells under Sch B pretreatment. Cell viability and PD feathers of 6-OHDA-induced PD mice were measured for neuroprotection assessment. The regulation of miR-34a on Nrf2 activity and expression was demonstrated through gain-of-function and loss of-function studies, while the regulatory role of miR-34a in the neuroprotection of Sch B was investigated both in vitro and in vivo. RESULTS: Sch B pretreatment ameliorated 6-OHDA-induced changes in vitro, like upregulated miR-34a expression, inhibited Nrf2 pathways and decreased cell survival, and PD feathers in vivo. Moreover, Nrf2 was negatively regulated by miR-34a, while miR-34a overexpression inhibited the neuroprotection of Sch B in both dopaminergic SH-SY5Y cells and PD mice. CONCLUSION: Sch B showed neuroprotective effect in 6-OHDA-induced PD pathogenesis, which could be inhibited by miR-34a, involving the negative regulatory mechanism of miR-34a on Nrf2 pathways. PMID- 26282219 TI - Non-thermal plasma-activated water inactivation of food-borne pathogen on fresh produce. AB - Non-thermal plasma has been widely considered to be an effective method for decontamination of foods. Recently, numerous studies report that plasma-activated water (PAW) also has outstanding antibacterial ability. This study presents the first report on the potential of PAW for the inactivation of Staphylococcus aureus (S. aureus) inoculated on strawberries. PAW treatments achieved a reduction of S. aureus ranging from 1.6 to 2.3 log at day-0 storage, while 1.7 to 3.4 log at day-4 storage. The inactivation efficiency depended on the plasma activated time for PAW generation and PAW-treated time of strawberries inoculated with S. aureus. LIVE/DEAD staining and scanning electron microscopy results confirm that PAW could damage the bacterial cell wall. Moreover, optical emission spectra and oxidation reduction potential results demonstrate the inactivation is mainly attributed to oxidative stress induced by reactive oxygen species in PAW. In addition, no significant change was found in color, firmness and pH of the PAW treated strawberries. Thus, PAW can be a promising alternative to traditional sanitizers applied in the fresh produce industry. PMID- 26282220 TI - Hydrogeochemistry of co-occurring geogenic arsenic, fluoride and iodine in groundwater at Datong Basin, northern China. AB - Abnormal levels of co-occurring arsenic (As), fluorine (F) and iodine (I) in groundwater at Datong Basin, northern China are geochemically unique. Hydrochemical, (18)O and (2)H characteristics of groundwater were analyzed to elucidate their mobilization processes. Aqueous As, F and I ranged from 5.6 to 2680 MUg/L, 0.40 to 3.32 mg/L and 10.1 to 186 MUg/L, respectively. High As, F and I groundwater was characterized by moderately alkaline, high HCO3(-), Fe(II), HS( ) and DOC concentrations with H3AsO3, F(-) and I(-) as the dominant species. The plots of delta(18)O values and Cl/Br ratios versus Cl(-) concentration demonstrate build-up of more oxidizing conditions and precipitation of carbonate minerals induced by vertical recharge and intensive evaporation facilitate As retention to Fe (hydr) oxides, but enhance F and I mobilization from host minerals. Under reducing conditions, As and I can be simultaneously released via reductive dissolution of Fe (hydr) oxides and reduction of As(V) and I(V) while F migration may be retarded due to effects of dissolution-precipitation equilibria between carbonate minerals and fluorite. With the prevalence of sulfate-reducing condition and lowering of HCO3(-) concentration, As and I may be sequestered by Fe(II) sulfides and F is retained to fluorite and on clay mineral surfaces. PMID- 26282221 TI - Effect of sound frequency and initial concentration on the sonochemical degradation of perfluorooctane sulfonate (PFOS). AB - Perfluoooctanesulfonic acid (PFOS) is a perfluorinated compound (PFC) highly resistant to conventional advance oxidation processes, which was widely used in industrial activities due to its surfactant nature, olephobic-hydrophobic properties, and chemical inertness. Sonochemical treatment has been suggested as an effective approach to treat aqueous solutions containing minimal levels of PFCs. This study investigates PFOS sonochemical degradation and its dependency on the initial concentration (10-460 MUM), and the applied sound frequency (25 and 500 kHz, and 1 MHz). PFOS was degraded by sonochemical treatment at concentrations as high as 460 MUM, as demonstrated by fluoride release and total organic content data. PFOS degradation rate was higher at megasonic frequencies (1MHz) compared to ultrasonic frequencies (25-500 kHz). PFOS degradation was controlled by saturation kinetics as indicated by an increase in PFOS degradation rate with increasing PFOS concentration until a maximum, after which the degradation rate was independent of the concentration. The saturation conditions were dependent on the sound frequency, and they were reached at a lower concentration under 1 MHz (100 MUM) compared to the 500 kHz frequency (>460 MUM). Overall, the results of this study demonstrate that high PFOS concentration can be effectively sonochemically treated using megasonic frequencies. PMID- 26282223 TI - Comparison between bioconcentration factor (BCF) data provided by industry to the European Chemicals Agency (ECHA) and data derived from QSAR models. AB - The bioconcentration factor (BCF) is the ratio of the concentration of a chemical in an organism to the concentration in the surrounding environment at steady state. It is a valuable indicator of the bioaccumulation potential of a substance. BCF is an essential environmental property required for regulatory purposes within the Registration, Evaluation, Authorization and restriction of Chemicals (REACH) and Globally Harmonized System (GHS) regulations. In silico models for predicting BCF can facilitate the risk assessment for aquatic toxicology and reduce the cost and number of animals used. The aim of the present study was to examine the correlation of BCF data derived from the dossiers of registered chemicals submitted to the European Chemical Agency (ECHA) with the results of a battery of Quantitative Structure-Activity Relationship (QSAR). After data pruning, statistical analysis was performed using the predictions of the selected models. Results in terms of R(2) had low rating around 0.5 for the pruned dataset. The use of the model applicability domain index (ADI) led to an improvement of the performance for compounds falling within it. The variability of the experimental data and the use of different parameters to define the applicability domain can influence the performance of each model. All available information should be adapted to the requirements of the regulation to obtain a safe decision. PMID- 26282222 TI - A Meta-Analysis of Executive Dysfunction and Antidepressant Treatment Response in Late-Life Depression. AB - OBJECTIVE: Depressed older adults with executive dysfunction (ED) may respond poorly to antidepressant treatment. ED is a multifaceted construct and different studies have measured different aspects of ED, making it unclear which aspects predict poor response. Meta-analytic methods were used to determine whether ED predicts poor antidepressant treatment response in late-life depression and to determine which domains of executive functioning are responsible for this relationship. METHODS: A Medline search was conducted to identify regimented treatment trials contrasting executive functioning between elderly responders and nonresponders; only regimented treatment trials for depressed outpatients aged 50 and older were included. Following the most recent PRISMA guidelines, 25 measures of executive functioning were extracted from eight studies. Six domains were identified: cognitive flexibility, planning and organization, response inhibition, selective attention, verbal fluency, and the Dementia Rating Scale Initiation/Perseveration composite score (DRS I/P). Hedge's g was calculated for each measure of executive functioning. A three-level Bayesian hierarchical linear model (HLM) was used to estimate effect sizes for each domain of executive functioning. RESULTS: The effect of planning and organization was significantly different from zero (Bayesian HLM estimate of domain effect size: 0.91; 95% CI: 0.32-1.58), whereas cognitive flexibility, response inhibition, selective attention, verbal fluency, and the DRS I/P composite score were not. CONCLUSION: The domain of planning and organization is meaningfully associated with poor antidepressant treatment response in late-life depression. These findings suggest that therapies that focus on planning and organization may provide effective augmentation strategies for antidepressant nonresponders with late-life depression. PMID- 26282225 TI - Serum perfluoroalkyl acids and time to pregnancy in nulliparous women. AB - BACKGROUND: Previous studies on the exposure to perfluoroalkyl acids (PFAAs) and female fertility have provided conflicting results. We aimed to investigate the association between several PFAAs and time to pregnancy among nulliparous women. METHODS: From 2008 to 2013, we included 1372 women from the Aarhus Birth Cohort, Aarhus University Hospital, Denmark, who provided data on time to pregnancy and a blood sample before 20 gestational weeks. We measured the levels of 16 PFAAs in maternal serum and report data for seven compounds with quantifiable values in at least 50% of samples. Fecundability ratios according to PFAA levels (quartiles or continuous levels) were estimated by discrete-time survival analyses, adjusted for potential confounders. We further investigated the association between PFAAs and infertility (time to pregnancy>12 months or infertility treatment prior to the studied pregnancy) by multivariable logistic regression. RESULTS: Median levels of perfluorooctane sulfonate and perfluorooctanoate were 8.3 and 2.0 ng/mL. Overall, no obvious associations were found between any PFAAs and fecundability or infertility. Adjusted fecundability ratios (95% confidence intervals) were 1.09 (0.92-1.29) for perfluorooctane sulfonate and 1.10 (0.93 1.30) for perfluorooctanoate (highest versus lowest quartile). CONCLUSIONS: We found no evidence of an association between present serum levels of PFAAs and longer time to pregnancy or infertility in nulliparous women. This study further adds to the sparse knowledge on PFAAs besides perfluorooctane sulfonate and perfluorooctanoate. PMID- 26282224 TI - Residential proximity to major roadways and incident hypertension in post menopausal women. AB - Living near major roadways has been associated with increased risk of cardiovascular morbidity and mortality, presumably from exposure to elevated levels of traffic-related air and/or noise pollution. This association may potentially be mediated through increased risk of incident hypertension, but results from prior studies are equivocal. Using Cox proportional hazards models we examined residential proximity to major roadways and incident hypertension among 38,360 participants of the Women's Health Initiative (WHI) Clinical Trial cohorts free of hypertension at enrollment and followed for a median of 7.9 years. Adjusting for participant demographics and lifestyle, trial participation, and markers of individual and neighborhood socioeconomic status, the hazard ratios for incident hypertension were 1.13 (95% CI: 1.00, 1.28), 1.03 (0.95, 1.11), 1.05 (0.99, 1.11), and 1.05 (1.00, 1.10) for participants living <=50, >50 200, >200-400, and >400-1000 m vs >1000 m from the nearest major roadway, respectively (ptrend=0.013). This association varied substantially by WHI study region with hazard ratios for women living <=50 m from a major roadway of 1.61 (1.18, 2.20) in the West, 1.51 (1.22, 1.87) in the Northeast, 0.89 (0.70, 1.14) in the South, and 0.94 (0.75, 1.19) in the Midwest. In this large, national cohort of post-menopausal women, residential proximity to major roadways was associated with incident hypertension in selected regions of the U.S. If causal, these results suggest residential proximity to major roadways, as a marker for air, noise and other traffic-related pollution, may be a risk factor for hypertension. PMID- 26282226 TI - Race/ethnicity and gender differences in mental health diagnoses among Iraq and Afghanistan veterans. AB - Veterans who served in Operation Enduring Freedom (OEF; predominantly in Afghanistan) and Operations Iraqi Freedom and New Dawn (OIF and OND; predominantly in Iraq) and are enrolled in the VA are comprised of a growing cohort of women and higher proportions of racial/ethnic minorities than civilians. To compare rates of mental health disorders by race/ethnicity and gender for this diverse cohort, we conducted a retrospective analysis of existing records from OEF/OIF/OND veterans who were seen at the VA 10/7/01-8/1/2013 (N=792,663). We found that race/ethnicity was related to diagnoses of mental health disorders. Asian/Pacific Islanders (A/PIs) were diagnosed with all disorders at lower rates than whites, and American Indian/Alaska Native (AI/AN) males were diagnosed with most disorders at higher rates than white males. Research is needed to identify contributing factors to differential rates of diagnoses based on race/ethnicity and gender. A/PIs and AI/ANs have unique patterns of mental health diagnoses indicating they should be considered separately to present a comprehensive picture of veteran mental health. PMID- 26282227 TI - Immigration and psychotic experiences in the United States: Another example of the epidemiological paradox? AB - In Europe, it is widely established that immigration increases risk for psychotic disorder. However, research has yet to confirm this association in the United States, where immigrants paradoxically report better health status than their native-born counterparts. Further, few studies have examined this topic with respect to sub-threshold psychotic experiences, which are more common than psychotic disorders in the general population. This study analyzes the (1) National Comorbidity Survey-Replication, (2) the National Latino and Asian American Survey, and (3) the National Survey of American Life, in order to determine whether generation status had any impact on risk for lifetime and 12 month PE, and whether these associations vary across racial/ethnic groups, adjusting for demographic variables and socioeconomic status. We found an absence of an immigration effect on PE across various ethnic groups and across various geographic areas, and found that immigration is actually protective among Latinos, supporting the idea that the epidemiological paradox extends to the psychosis phenotype. PMID- 26282228 TI - Influence of personality and neuropsychological ability on social functioning and self-management in bipolar disorder. AB - A majority of bipolar patients (BD) show functional difficulties even in remission. In recent years cognitive functions and personality characteristics have been associated with occupational and psychosocial outcomes, but findings are not consistent. We assessed personality and cognitive functioning through a range of tests in BD and control participants. Three cognitive domains-verbal memory, facial-executive, and spatial memory-were extracted by principal component analysis. These factors and selected personality dimensions were included in hierarchical regression analysis to predict psychosocial functioning and the use of self-management strategies while controlling for mood status. The best determinants of good psychosocial functioning were good verbal memory and high self-directedness. The use of self-management techniques was associated with a low level of harm-avoidance. Our findings indicate that strategies to improve memory and self-directedness may be useful for increasing functioning in individuals with bipolar disorder. PMID- 26282229 TI - Persistence with denosumab and persistence with oral bisphosphonates for the treatment of postmenopausal osteoporosis: a retrospective, observational study, and a meta-analysis. AB - The objectives of this study were to estimate persistence with denosumab and put these results in context by conducting a review of persistence with oral bisphosphonates. Persistence with denosumab was found to be higher than with oral bisphosphonates. PURPOSE: This study had two objectives: to analyse persistence in Swedish women initiating denosumab for treatment of postmenopausal osteoporosis (PMO) and to put these findings in context by conducting a literature review and meta-analysis of persistence data for oral bisphosphonates. METHODS: The study used the Swedish Prescribed Drug Register and included women aged at least 50 years initiating denosumab between May 2010 and July 2012. One injection of denosumab was defined as 6-month persistence. Women were considered persistent for another 6 months if they filled their next prescription within 6 months + 56 days and survival analysis applied to the data. A literature search was conducted in PubMed to identify retrospective studies of persistence with oral bisphosphonates and pooled persistence estimates were calculated using a random-effects model. RESULTS: The study identified 2,315 women who were incident denosumab users. Mean age was 74 years and 61% had been previously treated for PMO. At 12 and 24 months, persistence with denosumab was 83% (95% CI, 81-84%) and 62% (95% CI, 60-65%), respectively. The literature search identified 40 articles for inclusion in the meta-analysis. At 12 and 24 months, persistence with oral bisphosphonates ranged from 10% to 78% and from 16% to 46%, with pooled estimates of 45% and 30%, respectively. CONCLUSION: These data from the Swedish Prescribed Drug Register and literature review suggest that persistence was higher with denosumab than with oral bisphosphonates. PMID- 26282230 TI - Evaluation of a simplified hip structure analysis method for the prediction of incident hip fracture events. AB - Many attempts have been made to improve the predictive ability of areal bone mineral density (aBMD) which integrates bone mass and area. The addition of an extra variable derived from the hip dual-energy X-ray (DXA) image TR_sigma, which describes distribution of mass within the scanned area of the trochanter, improved prediction of 15-year hip fracture probability in elderly women. INTRODUCTION: Two-dimensional DXA imaging of the proximal femur to produce an aBMD is a clinically useful predictor of future fracture risk. Further analysis of the DXA image to produce an eight-variable hip structure analysis (Beck HSA) has been developed to improve understanding of structural factors determining hip bone strength at each of three proximal femur sites, the narrow femoral neck (NN), intertrochanter (TR) and shaft (S). Recently, data on four measurements derived from the currently used eight Beck HSA variables were used to capture population variation in bone structure at each site. These include two previously used variables, the localised aBMD and the sub-periosteal width (W) applying to 5 mm sections (at each sites), and two new variables, standard deviation of normalised mineral-mass projection profile distribution (sigma), and displacement between centre-of-mineral mass and geometric centre-of-mineral mass of projection profile (delta). METHODS: Using a cohort of 1159 women, mean baseline age 75, who sustained 139 hip fractures over 15 years, we determined whether these measures significantly improved 15-year hip fracture prediction compared to current approach utilising age and total hip aBMD. To describe the most parsimonious model for hip fracture risk prediction, the 12 base measures (4 from each site), total hip aBMD and age were evaluated in stepwise logistic regression models. RESULTS: The final model included TR_sigma, total hip aBMD and age and provided improved utility for hip fracture prediction compared to total hip aBMD and age alone (C-statistic 0.73 vs. 0.69, P = 0.009 and net reclassification improvement 0.164, P < 0.001, respectively). CONCLUSIONS: Addition of TR_sigma to total hip aBMD and age substantially improved prediction of 15-year hip fracture risk in this cohort of elderly women. PMID- 26282231 TI - CD147 reprograms fatty acid metabolism in hepatocellular carcinoma cells through Akt/mTOR/SREBP1c and P38/PPARalpha pathways. AB - BACKGROUND & AIMS: CD147 is a transmembrane glycoprotein which is highly expressed in various human cancers including hepatocellular carcinoma (HCC). A drug Licartin developed with (131)Iodine-labeled antibody against CD147 has been approved by the Chinese Food and Drug Administration (FDA) and enters into clinical use for HCC treatment. Increasing lines of evidence indicate that CD147 is implicated in the metabolism of cancer cells, especially glycolysis. However, the molecular mechanism underlying the relationship between CD147 and aberrant tumor lipid metabolism remains elusive. METHODS: We systematically investigated the role of CD147 in the regulation of lipid metabolism, including de novo lipogenesis and fatty acid beta-oxidation, in HCC cells and explored the underlying molecular mechanisms. RESULTS: Bioinformatic analysis and experimental evidence demonstrated that CD147 significantly contributed to the reprogramming of fatty acid metabolism in HCC cells mainly through two mechanisms. On one hand, CD147 upregulated the expression of sterol regulatory element binding protein 1c (SREBP1c) by activating the Akt/mTOR signaling pathway, which in turn directly activated the transcription of major lipogenic genes FASN and ACC1 to promote de novo lipogenesis. On the other hand, CD147 downregulated peroxisome proliferator activated receptor alpha (PPARalpha) and its transcriptional target genes CPT1A and ACOX1 by activating the p38 MAPK signaling pathway to inhibit fatty acid beta oxidation. Moreover, in vitro and in vivo assays indicated that the CD147 mediated reprogramming of fatty acid metabolism played a critical role in the proliferation and metastasis of HCC cells. CONCLUSION: Our findings demonstrate that CD147 is a critical regulator of fatty acid metabolism, which provides a strong line of evidence for this molecule to be used as a drug target in cancer treatment. PMID- 26282232 TI - Preventive administration of UDCA after liver transplantation for primary biliary cirrhosis is associated with a lower risk of disease recurrence. AB - BACKGROUND & AIMS: Recurrence of primary biliary cirrhosis (PBC) after liver transplantation (LT) is not rare and can occasionally lead to severe graft dysfunction and retransplantation. Ursodeoxycholic acid (UDCA) is a safe and effective treatment for PBC. However, whether preventive administration of UDCA after LT could lower the incidence of PBC recurrence is unknown. METHODS: Patients transplanted for PBC in five French and Swiss centers from 1988 to 2010 were included. Most patients from a single center received UDCA (10-15 mg/kg/d) preventively. Recurrence of PBC was histologically defined from biopsies routinely performed at 1, 5, 10, and 15 years of follow-up, and at any time when clinically indicated. RESULTS: A total of 90 patients with a 1-year minimum follow-up were studied retrospectively, including 19 (21%) patients receiving preventive UDCA. The mean follow-up was 12 years. Recurrence was diagnosed in 48 (53%) patients. The recurrence rates at 5, 10, and 15 years were 27%, 47%, and 61%, respectively. In a multivariate proportional hazards model adjusted for potential confounders and risk factors, preventive UDCA was the only factor affecting the risk of recurrence significantly (HR=0.32; 95% CI: 0.11-0.91). The 5, 10, and 15-year rates of recurrence were 11%, 21%, and 40%, respectively, under preventive UDCA, and 32%, 53%, and 70%, respectively, without preventive UDCA. Seven patients with recurrence (15%) progressed to cirrhosis, requiring retransplantation in one. However, neither recurrence nor preventive UDCA had a significant impact on survival. CONCLUSIONS: Preventive treatment with UDCA reduces the risk of PBC recurrence after LT. PMID- 26282233 TI - Serotonergic modulation of social status-dependent behavioural plasticity of the crayfish avoidance reaction. AB - Small crayfish usually showed escape-like dart responses to mechanical stimulation of the tailfan. Following agonistic bouts with conspecifics, dominant crayfish showed a defensive-like turn response to the same sensory stimulus. During the dart response, both uropods closed and animals walked forwards with the abdomen extended, while during the turn response the uropod on the stimulated side opened and animals turned towards the stimulus source with the abdomen frequently flexed. Using an isolated nerve cord preparation, we found that the spike activities of both the abdominal postural and uropod motor neurones in response to sensory stimulation of the exopodite reversed in dominant animals. In naive and subordinate animals, extensor motor neurones were excited and antagonistic flexor motor neurones inhibited in response to sensory stimulation. Furthermore, the spike frequency of uropod closer motor neurones increased while that of the antagonistic opener motor neurones decreased. By contrast, in more than half of the dominant animals, flexor and opener motor neurones showed excitatory responses while extensor and closer motor neurones showed inhibitory responses to the same sensory stimulation. This reverse of activity of the abdominal postural and uropod motor neurones was also observed when serotonin of more than 12.5 MUM in concentration was applied. PMID- 26282234 TI - Coding-complete sequencing classifies parrot bornavirus 5 into a novel virus species. AB - In this study, we determined the sequence of the coding region of an avian bornavirus detected in a blue-and-yellow macaw (Ara ararauna) with pathological/histopathological changes characteristic of proventricular dilatation disease. The genomic organization of the macaw bornavirus is similar to that of other bornaviruses, and its nucleotide sequence is nearly identical to the available partial parrot bornavirus 5 (PaBV-5) sequences. Phylogenetic analysis showed that these strains formed a monophyletic group distinct from other mammalian and avian bornaviruses and in calculations performed with matrix protein coding sequences, the PaBV-5 and PaBV-6 genotypes formed a common cluster, suggesting that according to the recently accepted classification system for bornaviruses, these two genotypes may belong to a new species, provisionally named Psittaciform 2 bornavirus. PMID- 26282235 TI - The complete genome sequences of two isolates of cnidium vein yellowing virus, a tentative new member of the family Secoviridae. AB - We determined the complete genome sequences of two isolates of cnidium vein yellowing virus (CnVYV-1 and -2) that co-infected all field samples collected from Cnidium officinale in Korea. Unlike CnVYV-2, however, CnVYV-1 was sap transmissible to Nicotiana benthamiana. CnVYV-1 and -2 have bipartite genomes of 7,263 and 3,110 nucleotides and 7,278 and 3,112 nucleotides, respectively, excluding the poly(A) tails. Phylogenetic analysis of the CnVYV-1 and -2 sequences indicated close relationships to strawberry latent ringspot virus, an unassigned member of the family Secoviridae. CnVYV-1 and CnVYV-2 are closely related viruses that may represent a tentative new species of the family Secoviridae. PMID- 26282236 TI - Comprehensive Assessment of Transcriptional Regulation Facilitates Metabolic Engineering of Isoprenoid Accumulation in Arabidopsis. AB - In plants, two spatially separated pathways provide the precursors for isoprenoid biosynthesis. We generated transgenic Arabidopsis (Arabidopsis thaliana) lines with modulated levels of expression of each individual gene involved in the cytosolic/peroxisomal mevalonate and plastidial methylerythritol phosphate pathways. By assessing the correlation of transgene expression levels with isoprenoid marker metabolites (gene-to-metabolite correlation), we determined the relative importance of transcriptional control at each individual step of isoprenoid precursor biosynthesis. The accumulation patterns of metabolic intermediates (metabolite-to-gene correlation) were then used to infer flux bottlenecks in the sterol pathway. The extent of metabolic cross talk, the exchange of isoprenoid intermediates between compartmentalized pathways, was assessed by a combination of gene-to-metabolite and metabolite-to-metabolite correlation analyses. This strategy allowed the selection of genes to be modulated by metabolic engineering, and we demonstrate that the overexpression of predictable combinations of genes can be used to significantly enhance flux toward specific end products of the sterol pathway. Transgenic plants accumulating increased amounts of sterols are characterized by significantly elevated biomass, which can be a desirable trait in crop and biofuel plants. PMID- 26282237 TI - Direct Recording of Trans-Plasma Membrane Electron Currents Mediated by a Member of the Cytochrome b561 Family of Soybean. AB - Trans-plasma membrane electron transfer is achieved by b-type cytochromes of different families, and plays a fundamental role in diverse cellular processes involving two interacting redox couples that are physically separated by a phospholipid bilayer, such as iron uptake and redox signaling. Despite their importance, no direct recordings of trans-plasma membrane electron currents have been described in plants. In this work, we provide robust electrophysiological evidence of trans-plasma membrane electron flow mediated by a soybean (Glycine max) cytochrome b561 associated with a dopamine beta-monooxygenase redox domain (CYBDOM), which localizes to the plasma membrane in transgenic Arabidopsis (Arabidopsis thaliana) plants and CYBDOM complementary RNA-injected Xenopus laevis oocytes. In oocytes, two-electrode voltage clamp experiments showed that CYBDOM-mediated currents were activated by extracellular electron acceptors in a concentration- and type-specific manner. Current amplitudes were voltage dependent, strongly potentiated in oocytes preinjected with ascorbate (the canonical electron donor for cytochrome b561), and abolished by mutating a highly conserved His residue (H292L) predicted to coordinate the cytoplasmic heme b group. We believe that this unique approach opens new perspectives in plant transmembrane electron transport and beyond. PMID- 26282238 TI - Changes in the Common Bean Transcriptome in Response to Secreted and Surface Signal Molecules of Rhizobium etli. AB - Establishment of nitrogen-fixing symbiosis requires the recognition of rhizobial molecules to initiate the development of nodules. Using transcriptional profiling of roots inoculated with mutant strains defective in the synthesis of Nod Factor (NF), exopolysaccharide (EPS), or lipopolysaccharide (LPS), we identified 2,606 genes from common bean (Phaseolus vulgaris) that are differentially regulated at early stages of its interaction with Rhizobium etli. Many transcription factors from different families are modulated by NF, EPS, and LPS in different combinations, suggesting that the plant response depends on the integration of multiple signals. Some receptors identified as differentially expressed constitute excellent candidates to participate in signal perception of molecules derived from the bacteria. Several components of the ethylene signal response, a hormone that plays a negative role during early stages of the process, were down regulated by NF and LPS. In addition, genes encoding proteins involved in small RNA-mediated gene regulation were regulated by these signal molecules, such as Argonaute7, a specific component of the trans-acting short interfering RNA3 pathway, an RNA-dependent RNA polymerase, and an XH/XP domain-containing protein, which is part of the RNA-directed DNA methylation. Interestingly, a number of genes encoding components of the circadian central oscillator were down-regulated by NF and LPS, suggesting that a root circadian clock is adjusted at early stages of symbiosis. Our results reveal a complex interaction of the responses triggered by NF, LPS, and EPS that integrates information of the signals present in the surface or secreted by rhizobia. PMID- 26282239 TI - Overaccumulation of gamma-Glutamylcysteine in a Jasmonate-Hypersensitive Arabidopsis Mutant Causes Jasmonate-Dependent Growth Inhibition. AB - Glutathione (GSH) is essential for many aspects of plant biology and is associated with jasmonate signaling in stress responses. We characterized an Arabidopsis (Arabidopsis thaliana) jasmonate-hypersensitive mutant (jah2) with seedling root growth 100-fold more sensitive to inhibition by the hormone jasmonyl-isoleucine than the wild type. Genetic mapping and genome sequencing determined that the mutation is in intron 6 of GLUTATHIONE SYNTHETASE2, encoding the enzyme that converts gamma-glutamylcysteine (gamma-EC) to GSH. The level of GSH in jah2 was 71% of the wild type, while the phytoalexin-deficient2-1 (pad2-1) mutant, defective in GSH1 and having only 27% of wild-type GSH level, was not jasmonate hypersensitive. Growth defects for jah2, but not pad2, were also seen in plants grown to maturity. Surprisingly, all phenotypes in the jah2 pad2-1 double mutant were weaker than in jah2. Quantification of gamma-EC indicated these defects result from hyperaccumulation of this GSH precursor by 294- and 65 fold in jah2 and the double mutant, respectively. gamma-EC reportedly partially substitutes for loss of GSH, but growth inhibition seen here was likely not due to an excess of total glutathione plus gamma-EC because their sum in jah2 pad2-1 was only 16% greater than in the wild type. Further, the jah2 phenotypes were lost in a jasmonic acid biosynthesis mutant background, indicating the effect of gamma-EC is mediated through jasmonate signaling and not as a direct result of perturbed redox status. PMID- 26282241 TI - Unilateral Ptosis. PMID- 26282240 TI - High-Resolution Three-Dimensional Structural Data Quantify the Impact of Photoinhibition on Long-Term Carbon Gain in Wheat Canopies in the Field. AB - Photoinhibition reduces photosynthetic productivity; however, it is difficult to quantify accurately in complex canopies partly because of a lack of high resolution structural data on plant canopy architecture, which determines complex fluctuations of light in space and time. Here, we evaluate the effects of photoinhibition on long-term carbon gain (over 1 d) in three different wheat (Triticum aestivum) lines, which are architecturally diverse. We use a unique method for accurate digital three-dimensional reconstruction of canopies growing in the field. The reconstruction method captures unique architectural differences between lines, such as leaf angle, curvature, and leaf density, thus providing a sensitive method of evaluating the productivity of actual canopy structures that previously were difficult or impossible to obtain. We show that complex data on light distribution can be automatically obtained without conventional manual measurements. We use a mathematical model of photosynthesis parameterized by field data consisting of chlorophyll fluorescence, light response curves of carbon dioxide assimilation, and manual confirmation of canopy architecture and light attenuation. Model simulations show that photoinhibition alone can result in substantial reduction in carbon gain, but this is highly dependent on exact canopy architecture and the diurnal dynamics of photoinhibition. The use of such highly realistic canopy reconstructions also allows us to conclude that even a moderate change in leaf angle in upper layers of the wheat canopy led to a large increase in the number of leaves in a severely light-limited state. PMID- 26282242 TI - Predicting violent behavior: The role of violence exposure and future educational aspirations during adolescence. AB - Few researchers have explored future educational aspirations as a promotive factor against exposure to community violence in relation to adolescents' violent behavior over time. The present study examined the direct and indirect effect of exposure to community violence prior to 9th grade on attitudes about violence and violent behavior in 12th grade, and violent behavior at age 22 via 9th grade future educational aspirations in a sample of urban African American youth (n = 681; 49% male). Multi-group SEM was used to test the moderating effect of gender. Exposure to violence was associated with lower future educational aspirations. For boys, attitudes about violence directly predicted violent behavior at age 22. For boys, future educational aspirations indirectly predicted less violent behavior at age 22. Implications of the findings and suggestions for future research are discussed. PMID- 26282243 TI - The molecular mechanism of Zinc acquisition by the neisserial outer-membrane transporter ZnuD. AB - Invading bacteria from the Neisseriaceae, Acinetobacteriaceae, Bordetellaceae and Moraxellaceae families express the conserved outer-membrane zinc transporter zinc uptake component D (ZnuD) to overcome nutritional restriction imposed by the host organism during infection. Here we demonstrate that ZnuD is required for efficient systemic infections by the causative agent of bacterial meningitis, Neisseria meningitidis, in a mouse model. We also combine X-ray crystallography and molecular dynamics simulations to gain insight into the mechanism of zinc recognition and transport across the bacterial outer-membrane by ZnuD. Because ZnuD is also considered a promising vaccine candidate against N. meningitidis, we use several ZnuD structural intermediates to map potential antigenic epitopes, and propose a mechanism by which ZnuD can maintain high sequence conservation yet avoid immune recognition by altering the conformation of surface-exposed loops. PMID- 26282244 TI - Targeted stellate decentralization: Implications for sympathetic control of ventricular electrophysiology. AB - BACKGROUND: Selective bilateral cervicothoracic sympathectomy has proven to be effective for managing ventricular arrhythmias in the setting of structural heart disease. In the procedure currently used, the caudal portions of both stellate ganglia along with thoracic chain ganglia down to T4 ganglia are removed. OBJECTIVE: The purpose of this study was to define the relative contributions of the T1-T2 and T3-T4 paravertebral ganglia in modulating ventricular electrical function. METHODS: In anesthetized vagotomized porcine subjects (n = 8), the heart was exposed via sternotomy along with right and left paravertebral sympathetic ganglia to the T4 level. A 56-electrode epicardial sock was placed over both ventricles to assess epicardial activation-recovery intervals (ARIs) in response to individually stimulating right and left stellate vs T3 paravertebral ganglia. Responses to T3 stimuli were repeated after surgical removal of the caudal portions of stellate ganglia and T2 bilaterally. RESULTS: In intact preparations, stellate ganglion vs T3 stimuli (4 Hz, 4-ms duration) were titrated to produce equivalent decreases in global ventricular ARIs (right side: 85 +/- 6 ms vs 55 +/- 10 ms; left side: 24 +/- 3 ms vs 17 +/- 7 ms). Threshold of stimulus intensity applied to T3 ganglia to achieve threshold was 3 times that of T1 threshold. ARIs in unstimulated states were unaffected by bilateral stellate-T2 ganglion removal. After acute decentralization, T3 stimulation failed to change ARIs. CONCLUSION: Preganglionic sympathetic efferents arising from the T1-T4 spinal cord that project to the heart transit through stellate ganglia via the paravertebral chain. Thus, T1-T2 surgical excision is sufficient to functionally interrupt central control of peripheral sympathetic efferent activity. PMID- 26282246 TI - Preface. PMID- 26282245 TI - Cardiac sodium channel mutation associated with epinephrine-induced QT prolongation and sinus node dysfunction. AB - BACKGROUND: Long-QT syndrome (LQTS) is an inherited arrhythmia characterized by prolonged ventricular repolarization and malignant tachyarrhythmias. LQT1, LQT2, and LQT3 are caused by mutations in KCNQ1 (LQT1), KCNH2 (LQT2), and SCN5A (LQT3), which account for approximately 90% of genotyped LQTS patients. Most cardiac events in LQT1 patients occur during exercise, whereas patients with LQT3 tend to have arrhythmic events during rest or asleep. OBJECTIVE: The study aimed to identify a genetic mutation in a Japanese man who presented with sinus node dysfunction and prolonged QT interval on exercise and epinephrine stress tests, as well as to clarify the electrophysiological properties of mutant channels. METHODS: LQTS-related genes were screened in this patient. Electrophysiological functional assays were conducted with a heterologous expression system. RESULTS: We identified a heterozygous missense SCN5A mutation, V2016M, which changes the last amino acid of the cardiac sodium channel. Electrophysiological analyses revealed that the mutant channels exhibited a loss-of-function feature, decreased peak sodium current densities (wild type 175.2 +/- 17.6 pA/pF; V2016M 97.2 +/- 16.0 pA/pF; P < .01). In addition, the mutant channels showed gain-of-function features: increased late sodium currents by protein kinase A activation (wild type 0.07 +/- 0.01%; V2016M 0.17 +/- 0.03%; P < .05) and impaired inactivation of sodium channels by protein kinase A or C activation. CONCLUSION: We identified an SCN5A mutation in a patient with sinus node dysfunction and epinephrine-induced QT prolongation, which was an atypical phenotype for LQT3. The electrophysiological properties of the mutant channels might be associated with the overlapping clinical features of the patient. PMID- 26282247 TI - In vitro and in vivo biocompatibility, bioavailability and tolerance of an injectable vehicle for adipose-derived stem/stromal cells for plastic surgery indications. AB - Soft tissue reconstruction is a challenge in plastic surgery, when replacing lost materials and correcting contour defects. Many permanent and temporary fillers have been used to restore the volume of these lesions, but often with poor results and even complications. Adipose-derived stem/stromal cells (ASCs) and adipose tissue engineering have been suggested as valuable alternatives. In order to inject these cultured cells, it was essential to find a suitable vehicle. The purpose of this study was to evaluate Cytocare((r)), an injectable medical device, composed of hyaluronic acid plus amino acids, vitamins and mineral salts. First, ASC viability and bioavailability in the 3 different available Cytocare((r)) formulations using the MTT test were assessed; then an animal experiment, testing the tolerance after intradermal injections of both Cytocare((r)) alone and with ASCs was carried out. Our in vitro results demonstrate a high biocompatibility of Cytocare((r)) resulting in a better viability of ASCs when cultured in Cytocare((r)) compared to culture medium (p < 0.05, Mann and Whitney). Cytocare((r)) also permits their bioavailability and proliferation, making it a potential transfer vehicle that can retain the cells before their integration around the recipient site. Finally, our animal experiment shows that the ASC + Cytocare((r)) combination is well tolerated. In conclusion, Cytocare((r)) can be used as a biocompatible scaffold for cultured ASCs in therapeutic treatments, ensuring ASC bioavailability, as well as evidence of excellent tolerance in nude mice. PMID- 26282248 TI - Orthostatic hypotension and right heart failure as the initial manifestation of intravenous leiomyomatosis. AB - A 36-year-old woman, who had a history of myomectomy, presented with lightheadedness after changing position from sitting to standing and effort related shortness of breath. Echocardiography demonstrated a hyperechoic elongated mobile mass extending from the inferior caval vein to the right atrium. The mass was surgically removed, and histological examination established the diagnosis of intravenous leiomyomatosis. This case caught the attention of our cardiology group to consider the diagnosis when an inferior caval vein or right atrium mass is found in a patient with a history of uterine leiomyomatosis. PMID- 26282249 TI - An Applied Mereology of the City: Unifying Science and Philosophy for Urban Planning. AB - Based on their research showing that growing cities follow basic principles, two theoretical physicists, Luis Bettencourt and Geoffrey West, call for researchers and professionals to contribute to a grand theory of urban sustainability. In their research, they develop a 'science of the city' to help urban planners address problems that arise from population increases. Although they provide valuable insights for understanding urban sustainability issues, they do not give planners a manageable way to approach such problems. I argue that developing an applied mereology to understand the concept of 'city identity' gives planners a theoretical device for addressing urban affairs, including ethical concerns. In turn, I devise a model of city identity to show how a 'philosophy of the city' contributes to a grand theory of urban sustainability. PMID- 26282251 TI - Preclinical research in critical care - the Australasian perspective. PMID- 26282250 TI - Acute toluene intoxication--clinical presentation, management and prognosis: a prospective observational study. AB - BACKGROUND: Toluene is one of the most widely abused inhaled drugs due to its acute neurologic effects including euphoria and subsequent depression. However, dangerous metabolic abnormalities are associated to acute toluene intoxication. It has been previously reported that rhabdomyolysis and acute hepatorenal injury could be hallmarks of the condition, and could constitute risk factors for poor outcomes. The objective was to describe the clinical presentation, to characterize the renal and liver abnormalities, the management and prognosis associated to acute toluene intoxication. METHODS: We prospectively assessed 20 patients that were admitted to a single center's emergency department from September 2012 to June 2014 with clinical and metabolic alterations due to acute toluene intoxication. RESULTS: The main clinical presentation consisted of weakness associated to severe hypokalemia and acidosis. Renal glomerular injury (proteinuria) is ubiquitous. Biliary tract injury (alkaline phosphatase and gamma glutamyl transpeptidase elevations) disproportional to hepatocellular injury is common. Rhabdomyolysis occurred in 80% of patients, probably due to hypokalemia and hypophosphatemia. There were three deaths, all female, and all associated with altered mental status, severe acidosis, hypokalemia and acute oliguric renal failure. The cause of death was in all cases due to cardiac rhythm abnormalities. CONCLUSION: The hallmarks of acute toluene intoxication are hypokalemic paralysis and metabolic acidosis. Liver injury and rhabdomyolysis are common. On admission, altered mental status, renal failure, severe acidemia and female gender (not significant in our study, but present in all three deaths) could be associated with a poor outcome, and patients with these characteristics should be considered to be treated in an intensive care unit. PMID- 26282252 TI - Persistent critical illness characterised by Australian and New Zealand ICU clinicians. AB - OBJECTIVE: To identify the characteristics of patients with "persistent critical illness" (PerCI), as perceived by Australian and New Zealand intensive care unit clinicians. Patients with PerCI were defined as those whose reason for being in the ICU was now more related to their ongoing critical illness than their original reason for admission to the ICU. DESIGN AND PARTICIPANTS: Using a web based survey, we recruited clinicians affiliated with the Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group (CTG) who cared for adults. Clinicians included doctors, nurses, physiotherapists, dietitians, research managers and others. We used the ANZICS-CTG mailing list to email a single request for anonymous participation. RESULTS: A total of 101 eligible clinicians responded to our survey. PerCI was believed to develop after a median of 10 days (IQR, 7-14 days), and to be somewhat uncommon (occurring in 10% of all ICU patients [IQR, 5%-15%], and in 50% of all patients with a prolonged ICU length of stay [IQR, 20%-60%]). Ninety per cent of respondents thought that patients with PerCI required ongoing invasive mechanical ventilation, and the most common problems were thought to be respiratory insufficiency (68%), delirium (59%) and acquired neuromuscular disease (54%). Ten per cent of patients with PerCI were expected to be alive and well and at home 6 months after ICU discharge, with another 15% alive and at home but requiring significant help. The remainder were expected to die within 6 months or to need institutional care. CONCLUSION: Patients with PerCI appear to be an identifiable group of ICU patients, with definable characteristics, substantial stress associated with their care, and poor perceived long-term outcomes. PMID- 26282253 TI - What do ICU doctors do? A multisite time and motion study of the clinical work patterns of registrars. AB - OBJECTIVE: To quantify the time that intensive care unit registrars spend on different work tasks with other health professionals and patients and using information resources, and to compare them with those of clinicians in general wards and the emergency department (ED). DESIGN, SETTING AND PARTICIPANTS: A prospective, observational time-and-motion study of two ICUs with a total of 71 beds at two major teaching hospitals in Sydney. Twenty-six registrars were observed between 08:00 and 18:00 on weekdays for a total of 160.52 hours. MAIN OUTCOME MEASURES: Proportions of time spent on different tasks, using specific information resources, working with other health professionals and patients, and rates of multitasking and interruptions. RESULTS: A total of 12 043 distinct tasks were observed. Registrars spent 69.2% of time working at patients' bedsides, 49.6% in professional communication and 39.0% accessing information resources. Half of their time (53.8%) was spent with other ICU doctors and 29.2% with nurses. Compared with doctors and nurses on general wards, and doctors in the ED, ICU registrars were more likely to multitask (40.1 times/hour [24.4% of their time]). ICU registrars had a higher interruption rate than ward clinicians, (4.2 times/hour), but a lower rate than ED doctors. CONCLUSIONS: Face-to-face communication and information seeking consume a vast proportion of ICU registrars' time. Multitasking and handling frequent interruptions characterise their work, and such behaviours may create an increased risk of task errors. Electronic clinical information systems may be particularly beneficial in this information-rich environment. PMID- 26282254 TI - Clinical review criteria and medical emergency teams: evaluating a two-tier rapid response system. AB - OBJECTIVES: To assess the prevalence of patients fulfilling clinical review criteria (CRC), to determine activation rates for CRC assessments, to compare baseline characteristics and outcomes of patients who fulfilled CRC with patients who did not, and to identify the documented nursing actions in response to CRC values. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional study using a retrospective medical record audit, in a universityaffiliated, tertiary referral hospital with a two-tier rapid response system in Melbourne, Australia. We used a convenience sample of hospital inpatients on general medical, surgical and specialist service wards admitted during a 24-hour period in 2013. MAIN OUTCOME MEASURES: Medical emergency team (MET) or code blue activation, unplanned intensive care unit admissions, hospital length of stay and inhospital mortality. For patients who fulfilled CRC or MET criteria during the 24- hour period, the specific criteria fulfilled, escalation treatments and outcomes were collected. RESULTS: Of the sample (N = 422), 81 patients (19%) fulfilled CRC on 109 occasions. From 109 CRC events, 66 patients (81%) had at least one observation fulfilling CRC, and 15 patients (18%) met CRC on multiple occasions. The documented escalation rate was 58 of 109 events (53%). The number of patients who fulfilled CRC and subsequent MET call activation criteria within 24 hours was significantly greater than the number who did not meet CRC (P < 0.001). CONCLUSIONS: About one in five patients reached CRC during the study period; these patients were about four times more likely to also fulfil MET call criteria. Contrary to hospital policy, escalation was not documented for about half the patients meeting CRC values. Despite the clarity of escalation procedures on the graphic observation chart, escalation remains an ongoing problem. Further research is needed on the impact on patient outcomes over time and to understand factors influencing staff response. PMID- 26282255 TI - Initial levels of organ failure, microbial findings and mortality in intensive care-treated primary, secondary and tertiary sepsis. AB - OBJECTIVE: Analysis of whether patients with primary, secondary and tertiary sepsis, defined by the presence or absence of recent systemic inflammation inducing events before the onset of sepsis, differ in clinical presentation, microbiological test results, treatment received and outcome. DESIGN, SETTING AND PARTICIPANTS: A retrospective observational study in a single, general intensive care unit, of all patients treated for severe sepsis or septic shock from 2006 to 2011. Patients with haematological malignancies, with immunosuppressive diseases or being treated with immunosuppressive drugs were excluded. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Sequential Organ Failure Assessment score, incidence of organ failure, microbiological results of blood cultures and mortality. RESULTS: We included 213 patients, who were classified as having primary (n = 121), secondary (n = 65) or tertiary sepsis (n = 27). The groups differed significantly in SOFA score, the incidence of kidney failure and coagulation failure at onset of sepsis in the ICU, as well as in blood culture findings. No differences in 7 day or 28-day mortality were seen, but the time of death occurred earlier among nonsurvivors in the primary sepsis group. CONCLUSIONS: Inflammatory insults before the onset of sepsis affect the clinical picture, blood microbial findings, and in non-survivors, the time of death. These results could, if validated in a prospective study, form a basis for a novel and simple strategy for stratifying patients in clinical studies for immunomodulation therapies in sepsis. PMID- 26282256 TI - Nutrition therapy in adult patients receiving extracorporeal membrane oxygenation: a prospective, multicentre, observational study. AB - OBJECTIVES: To describe current nutrition delivery practices and to identify barriers to nutrition in patients receiving venovenous or venoarterial extracorporeal membrane oxygenation (ECMO) in multiple centres in Australia and New Zealand. DESIGN, SETTING AND PARTICIPANTS: A prospective, multicentre, observational study, set in eight intensive care units in Australia and New Zealand, of adults treated with ECMO who were expected to receive enteral nutrition (EN) or parenteral nutrition (PN) therapy for > 72 hours. Data were collected from the start of ECMO until 7 days after ECMO cessation. RESULTS: There were 107 patients enrolled, with a median age of 42 years (interquartile range [IQR], 31-56 years), and 54 patients (50%) were men. EN was the most commonly delivered mode of nutrition (on 84% of days) although it was interrupted on 53% of days. The median interruption duration was 8 hours (IQR, 4-5 hours] per episode. The two most common barriers to EN delivery were fasting for a therapeutic or diagnostic procedure and high gastric residual volumes. Median daily calorie and protein deliveries from EN and/or PN were 1680 kcal (IQR, 960 2100 kcal) and 72 g (IQR, 42-98 g) of protein. For patients who received EN and/or PN, median calorie and protein deficits during the study period were -7118 kcal (IQR, -11 614 to -4510 kcal) and -325 g (IQR, - 525 to -188 g) of protein. CONCLUSIONS: EN was the most commonly used nutrition-delivery mode during ECMO treatment but was frequently interrupted. Compared with estimated calorie and protein requirements, lesser but reasonably acceptable amounts were delivered, although calorie and protein deficits still existed. PMID- 26282257 TI - Continuous intra-arterial blood glucose monitoring using quenched fluorescence sensing in intensive care patients after cardiac surgery: phase II of a product development study. AB - PURPOSE: Variations in blood glucose (BG), hyperglycaemia and hypoglycaemia are associated with adverse clinical outcomes in intensive care unit patients. Continuous glucose monitoring (CGM) offers the potential to improve BG control, leading to improved patient outcomes. In our product development study, we determined the safety and performance of the GluCath Intravascular CGM System for up to 48 hours in 20 patients admitted to the ICU after cardiac surgery. METHODS: The GluCath system uses a quenched chemical fluorescence mechanism to optically measure glucose in blood. After undergoing elective cardiac surgery, 20 patients had a GluCath sensor inserted through a preexisting radial artery (RA) catheter, and BG was monitored for up to 48 hours. Qualitative measures included effects on patient care, blood pressure monitoring, and ease of blood sampling through the arterial catheter. Safety assessment of the sensor involved ultrasound (US) monitoring for intra-arterial thrombi. Quantitative measures were the accuracy of the sensor in comparison with the reference analyser, and the proportion of paired BG measurements that were compliant with the ISO15197:2003 and CLSI POCT 12-A3 accuracy reference standards. BG was managed according to usual protocols. RESULTS: Twenty sensors were successfully deployed through pre-existing RA catheters and stayed in the RA of the 20 patients for between 6 and 48 hours, with a median time of 45.0 hours (interquartile range, 42.0-47.3 hours). Sixteen of the inserted sensors (80%) remained in situ for more than 40 hours. Three catheters were removed due to clinically significant sampling difficulty or waveform dampening. Two patients had US evidence of a thrombus; in neither patient was the sensor removed early, and there were no significant sequelae or adverse effects detected. For the 758 paired measurements available for performance analysis, reference BG values ranged between 5.3 mmol/L and 12.8 mmol/L. Of the 758 paired sensor measurements, 735 (97.0%) met the ISO15197:2003 criteria (within 20% of a reference measurement when BG is >= 4.2 mmol/L [75 mg/dL]), and 648 (85.5%) met the CLSI POCT 12-A3 criteria (within 12.5% of a reference measurement when the BG level is >= 5.6 mmol/L [100mg/dL] and within 0.67 mmol/L [12 mg/dL] when the BG level is < 5.6mmol/L [100 mg/dL]). The aggregate mean absolute relative difference (MARD) between the sensor and the reference BG was 6.4%, with individual sensor MARDs ranging from 3.6% to 12.4%. CONCLUSIONS: The GluCath system, using quenched fluorescence sensing, was safe and showed acceptable accuracy when deployed for up to 48 hours in ICU patients after elective cardiac surgery. PMID- 26282258 TI - High-flow nasal cannula use in a paediatric intensive care unit over 3 years. AB - OBJECTIVE: High-flow nasal cannula (HFNC) therapy is increasingly used in paediatric intensive care unit (PICU) patients, despite a paucity of studies. We describe its use over the 3 years since its implementation in our tertiary intensive care unit. DESIGN: The clinical database was used to identify PICU patients on HFNC therapy from 2011 to 2013. Patients were assessed for risk factors, underlying diagnosis, viral test results and cardiorespiratory parameters before and after HFNC therapy. RESULTS: Fifty-four children were included with a median age of 3.5 months (interquartile range [IQR], 1-10 months) and 59% were females. The commonest diagnosis was bronchiolitis (79%). HFNC therapy was successful in 78% of patients and failed for 12 (seven patients went on to CPAP treatment and five were intubated). The median time to HFNC therapy failure was 5.5 hours (IQR, 3.6-9 hours), with 75% of patients experiencing therapy failure by 8.25 hours. The failure rate was 50% in children with a primary diagnosis of congenital heart disease. There was a statistically significant difference between the mean respiratory rate at 1 hour in the success and failure groups (P = 0.037), despite similar respiratory rates at onset. HFNC therapy failure was associated with a longer PICU LOS (P = 0.04). CONCLUSION: HFNC therapy was successful in most patients. Most failures occurred within 8.25 hours. Use of HFNC for heart disease was associated with a high therapy failure rate (50%). PMID- 26282259 TI - Oxygenation targets, monitoring in the critically ill: a point prevalence study of clinical practice in Australia and New Zealand. AB - BACKGROUND: Many critically ill patients require supplemental oxygen. However, the optimal oxygen saturation measured by pulse oximetry (SpO2) in intensive care unit patients is unknown. OBJECTIVE: To evaluate clinical practice in Australia and New Zealand ICUs in relation to SpO2monitoring, prescription of SpO2targets by doctors, and upper and lower limits of tolerance of high and low SpO2levels by ICU bedside nurses. METHOD: Cross-sectional, observational study conducted on 2 days in 2013 involving adult patients in Australia and New Zealand ICUs. RESULTS: Data from 350 adult ICU patients were included. SpO2alarms were less likely to be disabled in patients who were invasively ventilated than in patients not receiving supplemental oxygen (4.8% v 15.1%; P = 0.02). In mechanically ventilated patients and non-ventilated patients receiving supplemental oxygen, the lower prescribed SpO2limit and the ICU bedside nurses' stated limits for action for low SpO2levels were 92% (interquartile range, 90%-94%). Upper SpO2limits were less frequently prescribed than lower SpO2limits (4.9% [95% CI, 3.0%- 7.7%] v 36.6% [95% CI, 31.7%-41.7%]); P < 0.01) and the observed SpO2exceeded the prescribed upper limit on 10/17 occasions (59%) when an upper limit was prescribed. CONCLUSION: Our findings suggest a relatively low level of vigilance in relation to prevention of high SpO2compared with low SpO2for adult patients in Australian and New Zealand ICUs. PMID- 26282260 TI - A practical approach to end-of-life care rapid response team calls. AB - ICU registrars frequency encounter RRT calls associated with EOLC during their training. Interventions involving EOLC appear to be some of the commonest interventions performed during RRT review. Therefore, training about the assessment an management of such calls should be provided to registrars who participate in RRT calls. The approach outlined here provides a framework for such training. PMID- 26282261 TI - Acid-base physiology: comments on 10 contentious assertions. PMID- 26282262 TI - Towards defining persistent critical illness and other varieties of chronic critical illness. AB - We hypothesise that there exists a substantial and growing group of "persistently critically ill" patients who appear to be intensive care unit-dependent because of a cascade of critical illnesses rather than their original ICU admitting diagnosis. These persistently critically ill patients are those who remain in the ICU because of ongoing complications of care that continue after their reason for admission has been treated and is no longer active. We believe such patients can be distinguished from patients currently labelled as "chronic critical illness" or "prolonged mechanical ventilation". We further believe that their primary problem is not simply failure to wean from mechanical ventilation due to muscle weakness and impaired gas exchange. We outline a program of clinician consultation, epidemiological research, consensus conference and validation to develop a useful definition of persistent critical illness, with the aim of supporting investigations in preventing persistence, and improving the care of patients so affected. PMID- 26282263 TI - Bedside placement of an endobronchial valve to aid invasive ventilation and weaning from extracorporeal membrane oxygenation. AB - A bronchopleural fistula (BPF) is a life-threatening complication of cardiothoracic surgery and acute illness. There is no consensus on how best to treat a BPF. Recently, endobronchial one-way valves, designed for bronchoscopic lung volume reduction in emphysema, have been used to treat BPFs. We describe the use of an endobronchial oneway valve, placed at the bedside via flexible bronchoscopy, to treat a BPF in a patient with hypoxic respiratory failure, supported by extracorporeal membrane oxygenation (ECMO), secondary to pneumonia. We believe that this is the first published description of this technique being used in a patient needing ECMO support. PMID- 26282264 TI - Loop diuretic therapy in the critically ill: a survey. AB - OBJECTIVES: To describe the self-reported practice of loop diuretic therapy (LDT) administration by intensivists in Australia and New Zealand and to ascertain the anticipated clinical and physiological effects of LDT for several common clinical indications. DESIGN: Structured online questionnaire distributed to intensivists via the Australian and New Zealand Intensive Care Society Clinical Trials Group email contact list. Descriptive statistics were used to analyse the results. PARTICIPANTS: Intensivists in Australia and New Zealand. RESULTS: A total of 146 intensivists responded to the survey with most (99 [67.8%]) being Fellows of the College of Intensive Care Medicine or the Joint Faculty of Intensive Care Medicine. Overall, 88 (60.2%) had worked in ICUs for 10 years or more. A positive fluid balance, acute pulmonary oedema (APO) and acute lung injury (ALI) were considered key indications for LDT (> 80.0% positive response), in contrast to an elevated central venous pressure (CVP) (20.3%) and acute kidney injury (AKI) (3.8%), which were not. LDT by bolus therapy was preferred (by 60.0%-89.4%, according to indication) over continuous infusion (3.6%- 11.1%, according to indication). The dominant initial LDT dose was furosemide 40 mg as an intravenous (IV) bolus. There was a lack of consensus regarding what would be an adequate response, and for many of the clinical indications, no target was specified. CONCLUSIONS: Australian and New Zealand intensivists typically give frusemide as a 40 mg IV bolus for a positive fluid balance, ALI and APO, but not for an elevated CVP or AKI. However, such therapy is given without explicit definitions of an adequate response under these different clinical circumstances. PMID- 26282265 TI - Single molecule magnet behaviour in a rare trinuclear {Cr(III)Dy} methoxo-bridged complex. AB - The reaction of the chromium(iii) chloride tetrahydrofuran complex with the dipivaloylmethane ligand, the lanthanide alcoholic salt DyCl3.CH3OH and the 1,1,1 tris(hydroxymethyl)-ethane ligand resulted in the formation of a new trinuclear chromium-dysprosium complex. Magnetic investigations revealed that the new 3d-4f complex exhibits single molecule magnet behaviour. PMID- 26282266 TI - Mild traumatic brain injury presenting with delayed intracranial hemorrhage in warfarin therapy: a case report. AB - INTRODUCTION: Current literature estimates the risk of delayed intracranial hemorrhage as between 0.6 and 6% after mild head injury for patients on warfarin. Due to resource allocation issues, the need to actually diagnose delayed intracranial haemorrhage has been questioned, especially if it does not require surgery. The purpose of our case report is to consider the functional implications during the six months following a mild traumatic brain injury complicated by delayed intracranial hemorrhage in a patient undergoing warfarin therapy. To the best of our knowledge, the rehabilitative and functional considerations of delayed intracranial haemorrhage in head injury have not been previously described in the literature. CASE PRESENTATION: A previously independent 74-year-old Lebanese man living in Australia sustained mild traumatic brain injury following an unwitnessed fall from the height of two meters while on warfarin therapy, with an international normalized ratio of 4.2. He was found to have amnesia of the event and extensive facial bruising. His Glasgow Coma Scale score was 14 to 15 throughout observation. Following a non-diagnostic initial computerised tomography scan, a repeat scan at 24 hours from the injury identified large intracerebral, subdural and subarachnoid hemorrhages. A detailed examination demonstrated visuospatial and cognitive impairments. He required inpatient rehabilitation for three weeks, and outpatient rehabilitation for two months. By six months, he had returned to his pre-injury level of functioning, but was unable to resume driving. CONCLUSIONS: We describe rehabilitation outcomes of delayed intracranial haemorrhage and mild traumatic brain injury, with diminishing disability over six months. In our case report, the complication of the delayed intracranial haemorrhage resulted in significant activity limitations and participation restrictions, which affected the clinical management, including the need for multidisciplinary rehabilitation. The risk of delayed intracranial haemorrhage in mild head injury remains a significant problem requiring further research. PMID- 26282267 TI - Xist localization and function: new insights from multiple levels. AB - In female mammals, one of the two X chromosomes in each cell is transcriptionally silenced in order to achieve dosage compensation between the genders in a process called X chromosome inactivation. The master regulator of this process is the long non-coding RNA Xist. During X-inactivation, Xist accumulates in cis on the future inactive X chromosome, triggering a cascade of events that provoke the stable silencing of the entire chromosome, with relatively few genes remaining active. How Xist spreads, what are its binding sites, how it recruits silencing factors and how it induces a specific topological and nuclear organization of the chromatin all remain largely unanswered questions. Recent studies have improved our understanding of Xist localization and the proteins with which it interacts, allowing a reappraisal of ideas about Xist function. We discuss recent advances in our knowledge of Xist-mediated silencing, focusing on Xist spreading, the nuclear organization of the inactive X chromosome, recruitment of the polycomb complex and the role of the nuclear matrix in the process of X chromosome inactivation. PMID- 26282268 TI - The effects of a dynamic patellar realignment brace on disease determinants for patellofemoral instability in the upright weight-bearing condition. AB - BACKGROUND: Patellar stabilizing braces are used to alleviate pain and prevent subluxation/dislocation by having biomechanical effects in terms of improved patellar tracking. The purpose of this study is to analyze the effects of the dynamic patellar realignment brace, Patella Pro (Otto Bock GmbH, Duderstadt, Germany), on disease determinants in subjects with patellofemoral instability using upright weight-bearing magnetic resonance imaging (MRI). METHODS: Twenty subjects (8 males and 12 females) with lateral patellofemoral instability were studied in an open-configuration magnetic resonance imaging scanner in an upright weight-bearing position at full extension (0 degrees flexion) and 15 degrees and 30 degrees flexion with and without the realignment brace. Disease determinants were defined by common patellofemoral indices that included the Insall-Salvati Index, Caton-Deschamps Index, and the Patellotrochlear Index to determine patella height and patella tilt angle, bisect offset, and tuberositas tibiae-trochlear groove (TT-TG) distance to determine patellar rotation and translation with respect to the femur and the alignment of the extensor mechanism. RESULTS: Analyses of variance revealed a significant effect of the brace with reduction of the three patellar height ratios, patella tilt angle, and bisect offset as well as TT-TG distance. Post hoc pairwise comparisons of the corresponding conditions with and without the realignment brace revealed significantly reduced patella height ratios, patella tilt angles, and bisect offsets at full extension and 15 degrees and 30 degrees flexion. No significant differences between the TT-TG distances at full extension but significant reductions at 15 degrees and 30 degrees flexion were observed when using the realignment brace compared to no brace. CONCLUSIONS: This study suggests that the dynamic patellar realignment brace is capable of improving disease determinants in the upright weight-bearing condition in the range of 0 degrees to 30 degrees flexion in patients with patellofemoral instability. PMID- 26282269 TI - Multistage carcinogenesis and the incidence of thyroid cancer in the US by sex, race, stage and histology. AB - BACKGROUND: Thyroid cancer has the fastest growing incidence in the US. However, the underlying causes are still under debate. METHODS: We analyzed thyroid cancer incidence in the SEER-9 registry from 1973-2010 using multistage carcinogenesis and age-period-cohort models. Multistage models were used to investigate differences in initiation, promotion and malignant conversion rates of thyroid tumors by sex, race, stage, and histology. Models were adjusted for period and cohort trends to investigate the contributions of each factor, and determine whether birth- or diagnosis-year better correlate with observed incidence patterns. RESULTS: Significant increases in thyroid cancer incidence by period or calendar-year were found for all sex, race, stage and histology combinations, particularly for localized cases (a 3- and 4-fold increase from 1973-2010 for females and males, respectively). Multistage analyses suggest that the 3-fold higher incidence in women could be explained by 1.5-fold higher initiation and promotion rates. Analyses by race suggest that the lower incidence in blacks can be attributed to lower promotion rates versus whites. Analysis by histology showed considerable decreases in follicular cancer incidence by birth-cohort since the early 1900s. CONCLUSIONS: Multistage modeling suggests that variations in thyroid cancer initiation and promotion can explain the observed differences in incidence by sex, race and histology. The consistent increases in incidence by calendar-year for all sex-race-histology-stage combinations suggest that the rise may be predominantly due to more intensive screening-diagnostics, although an environmental factor may be also at play. Our analyses constitute a first step towards the development of thyroid cancer natural history models. PMID- 26282270 TI - Morphology of the oxyurid nematodes Trypanoxyuris (T.) cacajao n. sp. and T. (T.) ucayalii n. sp. from the red uakari monkey Cacajao calvus ucayalii in the Peruvian Amazon. AB - Cacajao calvus ucayalii (Thomas, 1928) (Primates: Pitheciidae), a subspecies endemic to the Peruvian Amazon, occurs in patchy and sometimes isolated populations in north-eastern Peru and is in a vulnerable situation, mainly due to habitat loss and hunting. This rareness and remote distribution means that, until now, parasitical studies have been limited. Based on optical and scanning electron microscopy of specimens of both sexes, we report two new species of Trypanoxyuris pinworms occurring in the large intestine of the Peruvian red uakari, namely Trypanoxyuris (Trypanoxyuris) cacajao and Trypanoxyuris (Trypanoxyuris) ucayalii. Both species showed a distinct morphology of the lips and cephalic structure. Sexual dimorphism in the lateral alae was observed in both male and the female worms, with ventral ornamentation being shown in the oesophageal teeth. The finding of these new pinworm species highlights the possibility of discovering other species. PMID- 26282271 TI - Within-host evolution decreases virulence in an opportunistic bacterial pathogen. AB - BACKGROUND: Pathogens evolve in a close antagonistic relationship with their hosts. The conventional theory proposes that evolution of virulence is highly dependent on the efficiency of direct host-to-host transmission. Many opportunistic pathogens, however, are not strictly dependent on the hosts due to their ability to reproduce in the free-living environment. Therefore it is likely that conflicting selection pressures for growth and survival outside versus within the host, rather than transmission potential, shape the evolution of virulence in opportunists. We tested the role of within-host selection in evolution of virulence by letting a pathogen Serratia marcescens db11 sequentially infect Drosophila melanogaster hosts and then compared the virulence to strains that evolved only in the outside-host environment. RESULTS: We found that the pathogen adapted to both Drosophila melanogaster host and novel outside host environment, leading to rapid evolutionary changes in the bacterial life history traits including motility, in vitro growth rate, biomass yield, and secretion of extracellular proteases. Most significantly, selection within the host led to decreased virulence without decreased bacterial load while the selection lines in the outside-host environment maintained the same level of virulence with ancestral bacteria. CONCLUSIONS: This experimental evidence supports the idea that increased virulence is not an inevitable consequence of within-host adaptation even when the epidemiological restrictions are removed. Evolution of attenuated virulence could occur because of immune evasion within the host. Alternatively, rapid fluctuation between outside-host and within-host environments, which is typical for the life cycle of opportunistic bacterial pathogens, could lead to trade-offs that lower pathogen virulence. PMID- 26282272 TI - The camelliagenin from defatted seeds of Camellia oleifera as antibiotic substitute to treat chicken against infection of Escherichia coli and Staphylococcus aureus. AB - BACKGROUND: Escherichia coli and Staphylococcus aureus are the main pathogens infectious to poultry, and their resistances against antibiotics have become troublesome currently. Biofilm formation is an important reason for drug resistance. Our previous research has found that the extract of Camellia oleifera seeds has lots of pharmacological effects. In order to find the substitute for antibiotics, the saponin was isolated from the defatted C. oleifera seeds with structural identification. Its efficacy was evaluated by the inhibition on amoxicillin-resistant E. coli and erythromycin-resistant S. aureus and therapeutic effect on chicks infected by the two bacteria. RESULTS: The bacterial growth inhibition rate increased and the bacterial count in vivo decreased significantly in dose dependence after administration of the saponin and its combination with amoxicillin or erythromycin, suggesting its antibacterial effect. The saponin identified as camelliagenin shows significant inhibition on the biofilm of E. coli and S. aureus, and it is related to the decrease of mannitol dehydrogenase (MDH) activity and extracellular DNA (eDNA) content. Molecular simulation reveals the strong interaction existing between the saponin and MDH or eDNA. CONCLUSIONS: The mechanism of camelliagenin's improvement on antibiotic effects is its interaction with MDH and eDNA in biofilm. The saponin is a prospective substitute of antibiotics, and molecular simulation is a convenient alternative method to find out hopeful candidates of antibiotics substitute. PMID- 26282274 TI - Asymmetric top-down modulation of ascending visual pathways in pigeons. AB - Cerebral asymmetries are a ubiquitous phenomenon evident in many species, incl. humans, and they display some similarities in their organization across vertebrates. In many species the left hemisphere is associated with the ability to categorize objects based on abstract or experience-based behaviors. Using the asymmetrically organized visual system of pigeons as an animal model, we show that descending forebrain pathways asymmetrically modulate visually evoked responses of single thalamic units. Activity patterns of neurons within the nucleus rotundus, the largest thalamic visual relay structure in birds, were differently modulated by left and right hemispheric descending systems. Thus, visual information ascending towards the left hemisphere was modulated by forebrain top-down systems at thalamic level, while right thalamic units were strikingly less modulated. This asymmetry of top-down control could promote experience-based processes within the left hemisphere, while biasing the right side towards stimulus-bound response patterns. In a subsequent behavioral task we tested the possible functional impact of this asymmetry. Under monocular conditions, pigeons learned to discriminate color pairs, so that each hemisphere was trained on one specific discrimination. Afterwards the animals were presented with stimuli that put the hemispheres in conflict. Response patterns on the conflicting stimuli revealed a clear dominance of the left hemisphere. Transient inactivation of left hemispheric top-down control reduced this dominance while inactivation of right hemispheric top-down control had no effect on response patterns. Functional asymmetries of descending systems that modify visual ascending pathways seem to play an important role in the superiority of the left hemisphere in experience-based visual tasks. PMID- 26282275 TI - The Muller-Lyer illusion affects visuomotor updating in the dorsal visual stream. AB - To guide our actions, the brain has developed mechanisms to code target locations in egocentric coordinates (i.e., with respect to the observer), and to update these when the observer moves. The latter mechanism, called visuomotor updating, is implemented in the dorsal visual stream of the brain. In contrast, the ventral visual stream is assumed to transform target locations into an allocentric reference frame that is highly sensitive to visual contextual illusions. Here, we tested the effect of the Muller-Lyer illusion on visuomotor updating in a double step saccade task. Using the same paradigm in a 3T fMRI scanner, we investigated the effect of the illusion on the neural correlate of the updating process. Participants briefly viewed the Brentano version of the Muller-Lyer illusion with a target at its middle vertex, while fixating at one of the two endpoints of the illusion. Shortly after the disappearance of the stimulus, the eyes' fixation point moved to a position outside the illusion. After a delay, participants made a saccade to the remembered position of the target. The landing position of this saccade was systematically displaced in a manner congruent with the perceptual illusion, showing that visuomotor updating is affected by the illusion. fMRI results showed that the BOLD response in the occipito-parietal cortex (area V7) and the intraparietal sulcus related to planning of the saccade to the updated target was also modulated by the configuration of the illusion. This suggests that the dorsal visual stream represents perceived rather than physical locations of remembered saccade targets. PMID- 26282276 TI - Inferior frontal oscillations reveal visuo-motor matching for actions and speech: evidence from human intracranial recordings. AB - The neural correspondence between the systems responsible for the execution and recognition of actions has been suggested both in humans and non-human primates. Apart from being a key region of this visuo-motor observation-execution matching (OEM) system, the human inferior frontal gyrus (IFG) is also important for speech production. The functional overlap of visuo-motor OEM and speech, together with the phylogenetic history of the IFG as a motor area, has led to the idea that speech function has evolved from pre-existing motor systems and to the hypothesis that an OEM system may exist also for speech. However, visuo-motor OEM and speech OEM have never been compared directly. We used electrocorticography to analyze oscillations recorded from intracranial electrodes in human fronto-parieto temporal cortex during visuo-motor (executing or visually observing an action) and speech OEM tasks (verbally describing an action using the first or third person pronoun). The results show that neural activity related to visuo-motor OEM is widespread in the frontal, parietal, and temporal regions. Speech OEM also elicited widespread responses partly overlapping with visuo-motor OEM sites (bilaterally), including frontal, parietal, and temporal regions. Interestingly a more focal region, the inferior frontal gyrus (bilaterally), showed both visuo motor OEM and speech OEM properties independent of orolingual speech-unrelated movements. Building on the methodological advantages in human invasive electrocorticography, the present findings provide highly precise spatial and temporal information to support the existence of a modality-independent action representation system in the human brain that is shared between systems for performing, interpreting and describing actions. PMID- 26282279 TI - Obesity, paternalism and fairness. AB - Many liberal theories are committed to the promotion of population health, and the principle of non-interference in individual life plans. Public health interventions often bring out a tension between these two values. In this paper, I examine this tension by assessing the justifiability of liberty-restricting policies in the field of obesity prevention. As I want to show, a 'soft' form of paternalism, which interferes with people's choices to safeguard their true interests, goes some way in justifying such policies, but it leaves unaddressed the problem of limiting the liberty of those whose true interest is in pursuing an unhealthy lifestyle. I argue that in this latter case, the key to reconcile the promotion of population health with the respect for individual liberty is distributive justice: when we cannot help those who care about their health without doing the same for those who do not, fairness will often require us to do so. PMID- 26282280 TI - Experimental and computational studies of fatty acid distribution networks. AB - Unbalanced uptake of Omega 6/Omega 3 (omega-6/omega-3) ratios could increase chronic disease occurrences, such as inflammation, atherosclerosis, or tumor proliferation, and methylation methods for measuring the ruminal microbiome fatty acid (FA) composition/distribution play a vital role in discovering the contribution of food components to ruminant products (e.g., meat and milk) when pursuing a healthy diet. Hansch's models based on Linear Free Energy Relationships (LFERs) using physicochemical parameters, such as partition coefficients, molar refractivity, and polarizability, as input variables (Vk) are advocated. In this work, a new combined experimental and theoretical strategy was proposed to study the effect of omega-6/omega-3 ratios, FA chemical structure, and other factors over FA distribution networks in the ruminal microbiome. In step 1, experiments were carried out to measure long chain fatty acid (LCFA) profiles in the rumen microbiome (bacterial and protozoan), and volatile fatty acids (VFAs) in fermentation media. In step 2, the proportions and physicochemical parameter values of LCFAs and VFAs were calculated under different boundary conditions (cj) like c1 = acid and/or base methylation treatments, c2 = with/without fermentation, c3 = FA distribution phase (media, bacterial, or protozoan microbiome), etc. In step 3, Perturbation Theory (PT) and LFER ideas were combined to develop a PT-LFER model of a FA distribution network using physicochemical parameters (V(k)), the corresponding Box-Jenkins (DeltaV(kj)) and PT operators (DeltaDeltaV(kj)) in statistical analysis. The best PT-LFER model found predicted the effects of perturbations over the FA distribution network with sensitivity, specificity, and accuracy > 80% for 407 655 cases in training + external validation series. In step 4, alternative PT LFER and PT-NLFER models were tested for training Linear and Non-Linear Artificial Neural Networks (ANNs). PT-NLFER models based on ANNs presented better performance but are more complicated than the PT-LFER model. Last, in step 5, the PT-LFER model based on LDA was used to reconstruct the complex networks of perturbations in the FA distribution and compared the giant components of the observed and predicted networks with random Erdos-Renyi network models. In short, our new PT-LFER model is a useful tool for predicting a distribution network in terms of specific fatty acid distribution. PMID- 26282281 TI - Peritoneal dialysis as a treatment option in autosomal dominant polycystic kidney disease. AB - PURPOSE: When choosing a dialysis option for ADPKD patients, peritoneal dialysis (PD) is often discouraged, due to its potential drawbacks: risk of abdominal hernias and dialysis fluid leaks, risk of peritonitis and insufficient dialysis adequacy. The present study was designed to compare the outcomes and dialysis efficacy in ADPKD patients treated with PD, in comparison with non-ADPKD subjects. METHODS: This study was a retrospective analysis of the data from the national PD registry in which 106 ADPKD and 1606 non-ADPKD incident PD patients were evaluated. Data on dialysis adequacy, risk of dialysis-associated complications, as well as patient and technique survival were compared between the groups. RESULTS: The ADPKD patients did not differ from the non-ADPKD controls in terms of dialysis adequacy. After a median observation time of 32 months, there were no differences in patient or technique survival. The risk of abdominal hernias and dialysis fluid leaks was twice as high in ADPKD subjects, compared to the non-ADPKD group. However, these complications did not result in a need for a permanent transfer to hemodialysis. CONCLUSIONS: Dialysis adequacy, and patient and technique survival are similar in the ADPKD and non-ADPKD patients treated with PD. PD seems a feasible treatment option for end-stage renal failure in the course of ADPKD. PMID- 26282282 TI - Serine/arginine-rich splicing factor 3 (SRSF3) regulates homologous recombination mediated DNA repair. AB - BACKGROUND: Our previous work found that serine/arginine-rich splicing factor 3 (SRSF3) was overexpressed in human ovarian cancer and the overexpression of SRSF3 was required for ovarian cancer cell growth and survival. The mechanism underlying the role of SRSF3 in ovarian cancer remains to be addressed. METHODS: We conducted microarray analysis to profile the gene expression and splicing in SRSF3-knockdown cells and employed quantitative PCR and western blotting to validate the profiling results. We used chromatin immunoprecipitation to study transcription and the direct repeat green fluorescent protein reporter assay to study homologous recombination-mediated DNA repair (HRR). RESULTS: We identified 687 genes with altered expression and 807 genes with altered splicing in SRSF3 knockdown cells. Among expression-altered genes, those involved in HRR, including BRCA1, BRIP1 and RAD51, were enriched and were all downregulated. We demonstrated that the downregulation of BRCA1, BRIP1 and RAD51 expression was caused by decreased transcription and not due to increased nonsense-mediated mRNA decay. Further, we found that SRSF3 knockdown impaired HRR activity in the cell and increased the level of gamma-H2AX, a biomarker for double-strand DNA breaks. Finally, we observed that SRSF3 knockdown changed splicing pattern of KMT2C, a H3K4-specific histone methyltransferase, and reduced the levels of mono- and trimethylated H3K4. CONCLUSION: These results suggest that SRSF3 is a new regulator of HRR process, which possibly regulates the expression of HRR-related genes indirectly through an epigenetic pathway. This new function of SRSF3 not only explains why overexpression of SRSF3 is required for ovarian cancer cell growth and survival but also offers a new insight into the mechanism of the neoplastic transformation. PMID- 26282273 TI - Cannabinoids and Epilepsy. AB - Cannabis has been used for centuries to treat seizures. Recent anecdotal reports, accumulating animal model data, and mechanistic insights have raised interest in cannabis-based antiepileptic therapies. In this study, we review current understanding of the endocannabinoid system, characterize the pro- and anticonvulsive effects of cannabinoids [e.g., Delta9-tetrahydrocannabinol and cannabidiol (CBD)], and highlight scientific evidence from pre-clinical and clinical trials of cannabinoids in epilepsy. These studies suggest that CBD avoids the psychoactive effects of the endocannabinoid system to provide a well tolerated, promising therapeutic for the treatment of seizures, while whole-plant cannabis can both contribute to and reduce seizures. Finally, we discuss results from a new multicenter, open-label study using CBD in a population with treatment resistant epilepsy. In all, we seek to evaluate our current understanding of cannabinoids in epilepsy and guide future basic science and clinical studies. PMID- 26282283 TI - Increased vitamin D levels at birth and in early infancy increase offspring allergy risk-evidence for involvement of epigenetic mechanisms. PMID- 26282284 TI - Group 2 innate lymphoid cells mediate ozone-induced airway inflammation and hyperresponsiveness in mice. AB - BACKGROUND: Asthmatic patients are highly susceptible to air pollution and in particular to the effects of ozone (O3) inhalation, but the underlying mechanisms remain unclear. OBJECTIVE: Using mouse models of O3-induced airway inflammation and airway hyperresponsiveness (AHR), we sought to investigate the role of the recently discovered group 2 innate lymphoid cells (ILC2s). METHODS: C57BL/6 and BALB/c mice were exposed to Aspergillus fumigatus, O3, or both (3 ppm for 2 hours). ILC2s were isolated by means of fluorescence-activated cell sorting and studied for Il5 and Il13 mRNA expression. ILC2s were depleted with anti-Thy1.2 mAb and replaced by means of intratracheal transfer of ex vivo expanded Thy1.1 ILC2s. Cytokine levels (ELISA and quantitative PCR), inflammatory cell profile, and AHR (flexiVent) were assessed in the mice. RESULTS: In addition to neutrophil influx, O3 inhalation elicited the appearance of eosinophils and IL-5 in the airways of BALB/c but not C57BL/6 mice. Although O3-induced expression of IL-33, a known activator of ILC2s, in the lung was similar between these strains, isolated pulmonary ILC2s from O3-exposed BALB/c mice had significantly greater Il5 and Il13 mRNA expression than C57BL/6 mice. This suggested that an altered ILC2 function in BALB/c mice might mediate the increased O3 responsiveness. Indeed, anti-Thy1.2 treatment abolished but ILC2s added back dramatically enhanced O3-induced AHR. CONCLUSIONS: O3-induced activation of pulmonary ILC2s was necessary and sufficient to mediate asthma-like changes in BALB/c mice. This previously unrecognized role of ILC2s might help explain the heightened susceptibility of human asthmatic airways to O3 exposure. PMID- 26282286 TI - Piezoelectric Effects of Applied Electric Fields on Hydrogen-Bond Interactions: First-Principles Electronic Structure Investigation of Weak Electrostatic Interactions. AB - The piezoelectric properties of 2-methyl-4-nitroaniline crystals were explored qualitatively and quantitatively using an electrostatically embedded many-body (EE-MB) expansion scheme for the correlation energies of a system of monomers within the crystal. The results demonstrate that hydrogen bonding is an inherently piezoelectric interaction, deforming in response to the electrostatic environment. We obtain piezo-coefficients in excellent agreement with the experimental values. This approach reduces computational cost and reproduces the total resolution of the identity (RI)-Moller-Plesset second-order perturbation theory (RI-MP2) energy for the system to within 1.3 * 10(-5)%. Furthermore, the results suggest novel ways to self-assemble piezoelectric solids and suggest that accurate treatment of hydrogen bonds requires precise electrostatic evaluation. Considering the ubiquity of hydrogen bonds across chemistry, materials, and biology, a new electromechanical view of these interactions is required. PMID- 26282285 TI - GATA3 haploinsufficiency does not block allergic sensitization or atopic disease. PMID- 26282287 TI - Surface Plasmon Coupling of Compositionally Heterogeneous Core-Satellite Nanoassemblies. AB - Understanding plasmon coupling between compositionally heterogeneous nanoparticles in close proximity is intriguing and fundamentally important because of the energy mismatch between the localized surface plasmons of the associated nanoparticles and interactions beyond classical electrodynamics. In this Letter, we explore surface plasmon coupling between silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs), assembled in the form of core-satellite structures. A recently developed assembly method allows us to prepare ultrapure core-satellite nanoassemblies in solution, where 50 nm AgNPs are surrounded by 13 nm AuNPs via alkanedithiol linkers. We observe changes in the plasmon coupling between the AgNP core and AuNP satellites as the core-to-satellite gap distance varies from 2.3 to 0.7 nm. Comparison with theoretical studies reveals that the traditional hybridized plasmon modes are abruptly replaced by charge-transfer plasmons at a ~1 nm gap. Changes with the number of satellites are also discussed. PMID- 26282288 TI - Role of Oxygen Mass Transport in Rechargeable Li/O2 Batteries Operating with Ionic Liquids. AB - The use of ionic liquid (IL)-based electrolytes and porous carbonaceous cathodes is today one of the most promising strategies for the development of rechargeable Li/O2 batteries. Enhancing Li/O2 battery cyclability at high discharge rate is a key issue for automotive applications. O2 reduction at a meso-macroporous carbon electrode in N-butyl-N-methyl pyrrolidinium bis(trifluoromethanesulfonyl)imide (PYR14TFSI):LiTFSI 9:1 is here investigated. The study demonstrates that oxygen electrode response in IL at high discharge currents is dominated by O2 mass transport in IL. A novel configuration of flow-Li/O2 battery that operates at high discharge rate is reported. PMID- 26282289 TI - Excited-State Proton-Transfer Processes of DHICA Resolved: From Sub-Picoseconds to Nanoseconds. AB - Excited-state proton transfer has been hypothesized as a mechanism for UV energy dissipation in eumelanin skin pigments. By using time-resolved fluorescence spectroscopy, we show that the previously proposed, but unresolved, excited-state intramolecular proton transfer (ESIPT) of the eumelanin building block 5,6 dihydroxyindole-2-carboxylic acid (DHICA) occurs with a time constant of 300 fs in aqueous solution but completely stops in methanol. The previously disputed excited-state proton transfer involving the 5- or 6-OH groups of the DHICA anion is now found to occur from the 6-OH group to aqueous solvent with a rate constant of 4.0 * 10(8) s(-1). PMID- 26282290 TI - Chiral Hydrogen Bond Environment Providing Unidirectional Rotation in Photoactive Molecular Motors. AB - Generation of a chiral hydrogen bond environment in efficient molecular photoswitches is proposed as a novel strategy for the design of photoactive molecular motors. Here, the following strategy is used to design a retinal-based motor presenting singular properties: (i) a single excitation wavelength is needed to complete the unidirectional rotation process (360 degrees ); (ii) the absence of any thermal step permits the process to take place at low temperatures; and (iii) the ultrafast process permits high rotational frequencies. PMID- 26282291 TI - Stable Organic Monolayers on Oxide-Free Silicon/Germanium in a Supercritical Medium: A New Route to Molecular Electronics. AB - Oxide-free Si and Ge surfaces have been passivated and modified with organic molecules by forming covalent bonds between the surfaces and reactive end groups of linear alkanes and aromatic species using single-step deposition in supercritical carbon dioxide (SCCO2). The process is suitable for large-scale manufacturing due to short processing times, simplicity, and high resistance to oxidation. It also allows the formation of monolayers with varying reactive terminal groups, thus enabling formation of nanostructures engineered at the molecular level. Ballistic electron emission microscopy (BEEM) spectra performed on the organic monolayer on oxide-free silicon capped by a thin gold layer reveals for the first time an increase in transmission of the ballistic current through the interface of up to three times compared to a control device, in contrast to similar studies reported in the literature suggestive of oxide-free passivation in SCCO2. The SCCO2 process combined with the preliminary BEEM results opens up new avenues for interface engineering, leading to molecular electronic devices. PMID- 26282292 TI - Remarkable Photophysics and Amplified Quenching of Conjugated Polyelectrolyte Oligomers. AB - We report the photophysics and fluorescence quenching of a series of monodisperse, anionic pi-conjugated oligomers that are molecularly dissolved in aqueous solution. These structurally well-defined oligomers feature oligo(phenylene ethynylene) backbones with two -CH2COO(-) units on each repeat unit, with overall lengths of 5, 7, and 9 repeats. The ionic oligomers display a structured fluorescence band with high quantum efficiency in water, in contrast to the low fluorescence quantum efficiency and pronounced aggregation displayed by structurally similar oligomeric and polymeric (phenylene ethynylene) conjugated polyelectrolytes studied previously. Stern-Volmer (SV) fluorescence quenching studies using cationic charge- and energy-transfer quenchers reveal that all of the oligomers give rise to SV quenching constants (KSV) in excess of 10(6) M(-1), with values increasing with oligomer length, consistent with the amplified quenching effect. The amplified quenching effect is proposed to occur due to the formation of comparatively small oligomer aggregates. PMID- 26282293 TI - Catalytic Role of Surface Oxygens in TiO2 Photooxidation Reactions: Aqueous Benzene Photooxidation with Ti(18)O2 under Anaerobic Conditions. PMID- 26282294 TI - Ionic and Molecular Liquids: Working Together for Robust Engineering. AB - Because of their outstanding versatility, room-temperature ionic liquids (RTILs) are utilized in an ever increasing number of novel and fascinating applications, making them the Holy Grail of modern materials science. In this Perspective, we address the fundamental research and prospective applications of RTILs in combination with molecular liquids, concentrating on three significant areas: (1) the use of molecular liquids to decrease the viscosity of RTILs; (2) the role of RTIL micelle formation in water and organic solvents; and (3) the ability of RTILs to adsorb pollutant gases. Current achievements are examined, and future directions for the potential uses of RTILs are outlined. PMID- 26282295 TI - Beyond the Periodic Table of Elements: The Role of Superatoms. AB - Atomic clusters composed of homo or heteroatomic species constitute an intermediate phase of matter where every atom counts and whose properties depend on their size, shape, composition, and charge. If specific clusters mimicking the chemistry of atoms can be produced, they can be thought of as man-made superatoms forming the building blocks of a new three-dimensional periodic table. Novel materials with tailored properties can then be synthesized by assembling these superatoms. This invited Perspective presents a brief summary of the pioneering works that led to this concept, and highlights the recent breakthroughs that hold promise for a new era in materials science. PMID- 26282296 TI - Carrier Mobility in Graphyne Should Be Even Larger than That in Graphene: A Theoretical Prediction. AB - We show here that the carrier mobility in the novel sp-sp(2) hybridization planar 6,6,12-graphyne sheet should be even larger than that in the graphene sheet. Both graphyne and graphene exhibit a Dirac cone structure near the Fermi surface. However, due to the sp-sp(2) hybridization forming the triple bonds in graphyne, the electron-phonon scattering is reduced compared with that of graphene. The carrier mobility is calculated at the first-principles level by using the Boltzmann transport equation coupled with the deformation potential theory. The intrinsic mobility of the 6,6,12-graphyne is 4.29 * 10(5) cm(2) V(-1) s(-1) for holes and 5.41 * 10(5) cm(2) V(-1) s(-1) for electrons at room temperature, which is found to be larger than that of graphene (~ 3 * 10(5) cm(2) V(-1) s(-1)). PMID- 26282297 TI - Reproducible Deep-UV SERRS on Aluminum Nanovoids. AB - Surface-enhanced Raman scattering (SERS) with deep-UV excitation is of particular interest because a large variety of biomolecules such as amino acids exhibit electronic transitions in the UV spectral range and resonant excitation dramatically increases the cross section of the associated vibrational modes. Despite its potential, UV-SERS is still little-explored. We present a novel straightforward scalable route to fabricate aluminum nanovoids for reproducible SERS in the deep-UV without the need of expensive lithographic techniques. We adopt a modified template stripping method utilizing a soluble template and self assembled polymer spheres to create nanopatterned aluminum films. We observe high surface enhancement of approximately 6 orders of magnitude, with excitation in the deep-UV (244 nm) on structures optimized for this wavelength. This work thus enables sensitive detection of organics and biomolecules, normally nonresonant at visible wavelengths, with deep-UV surface-enhanced resonant Raman scattering on reproducible and scalable substrates. PMID- 26282298 TI - Effect of Packing on Formation of Deep Carrier Traps in Amorphous Conjugated Polymers. AB - We theoretically investigate the role of conformational disorder and intermolecular interactions on the localization properties of electronic states, leading to the formation of carrier traps in amorphous aggregates of conjugated polymers. Samples of amorphous conformations of poly(p-phenylene vinylene) (PPV), poly2-methoxy-5-(2-ethyl-hexyloxy)PPV (MEH-PPV), and [poly-(9,9'-dioctyluorene)] (PFO) oligomers are simulated by classical molecular dynamics, while their electronic structure is calculated using first-principles density functional theory. Localization and delocalization properties of molecular orbitals are studied based on the participation ratio analysis, an approach commonly used in inorganic semiconductors. Our simulations confirm that the alkyl side chains insignificantly affect the conformational disorder in amorphous polymers while having a dramatic effect on the intermolecular disorder and packing. The nature of the disorder and its impact on charge-carrier localization in amorphous polymers with alkyl side chains differ drastically from those of disordered polymers without side chains, such as PPVs. Thus, long-range intermolecular interactions and sparse packing are responsible for the formation of multiple, deep, highly localized trap states in amorphous MEH-PPVs and PFOs, while close packing in combination with conformational disorder leads to the trap states distributed mostly near the bandgap edges in PPV aggregates. PMID- 26282299 TI - Metrological Investigation of the (6,5) Carbon Nanotube Absorption Cross Section. AB - Using single-nanotube absorption microscopy, we measured the absorption cross section of (6,5) carbon nanotubes at their second-order optical transition. We obtained a value of 3.2 * 10(-17) cm(2)/C atom with a precision of 15% and an accuracy below 20%. This constitutes the first metrological investigation of the absorption cross section of chirality-identified nanotubes. Correlative absorption-luminescence microscopies performed on long nanotubes reveal a direct manifestation of exciton diffusion in the nanotube. PMID- 26282300 TI - Single-Nanocrystal Photoluminescence Spectroscopy Studies of Plasmon-Multiexciton Interactions at Low Temperature. AB - Using thick-shell or "giant" CdSe/CdS nanocrystal quantum dots (g-NQDs), characterized by strongly suppressed Auger recombination, we studied the influence of plasmonic interactions on multiexciton emission. Specifically, we assessed the separate effects of plasmonic absorption and plasmonic emission enhancement by a systematic analysis of the pump fluence dependence of low temperature photoluminescence (low-T PL) derived from individual CdSe/CdS g-NQDs deposited on nanoroughened silver films. Our study reveals that (1) the multiexciton (MX) emissions in g-NQD coupled to silver films were enhanced not only through the creation of more excitons via enhancement of absorption but also through the direct modification of the competition between the radiative and nonradiative recombination processes of MXs; (2) strong enhancement in absorption is not necessary for strong multiexciton emission; and (3) the emission of MXs can become stronger with the increase of multiexciton order. We also exploited the strong enhancement of MX emission to perform second-order photon correlation and cross-correlation experiments using very low pump fluences and observed a strong photon bunching that decays with increasing pump fluence. PMID- 26282301 TI - Nature of Excess Electrons in Polar Fluids: Anion-Solvated Electron Equilibrium and Polarized Hole-Burning in Liquid Acetonitrile. PMID- 26282302 TI - Differences in Ion Interactions for Isoelectronic Ionic Liquid Homologs. AB - Specific cation-anion interactions for two pairs of isoelectronic ionic liquids (ILs) have been investigated using nuclear Overhauser effect (NOE) 2D NMR methods to explore proximities between ions. The four ILs comprise the bis(trifluoromethylsulfonyl)amide anion paired with the following cations: triethyloctylammonium, (2-ethoxyethoxy)ethyltriethylammonium, triethyloctylphosphonium, and (2-ethoxyethoxy)ethyltriethylphosphonium. Substantial interactions are observed between the anion (19)F nuclei and all of the protons on the triethyl chains for each of the four cationic head groups. Significantly different interactions are observed for each of the four cationic tail groups and the anions. PMID- 26282303 TI - Structural Modification of Graphene Sheets to Create a Dense Network of Defect Sites. AB - Pt/graphene composites were synthesized by loading platinum nanoparticles onto graphene and etched at 1000 degrees C in a hydrogen atmosphere. This results in the formation of a dense array of nanostructured defect sites in the graphene, including trenches, nanoribbons, islands, and holes. These defect sites result in an increase in the number of unsaturated carbon atoms and, consequently, enhance the interaction of the CO2 molecules with the etched graphene. This leads to a high capacity for storing CO2; 1 g of the etched samples can store up to 76.3 cm(3) of CO2 at 273 K under ambient pressure. PMID- 26282304 TI - Nanocarbon Hybrids: The Paradigm of Nanoscale Self-Ordering/Self-Assembling by Means of Charge Transfer/Doping Interactions. AB - The scope of this Perspective is to highlight the potential of nanoscale self ordering/self-assembling nanocarbons-fullerenes, single-wall carbon nanotubes, and graphene-en route toward novel charge transfer hybrids that unify several functions such as light harvesting, charge separation, and, eventually, catalysis. All of the given examples are fully characterized by a broad range of spectroscopic as well as microscopic techniques and, as such, document the success in tuning the electronic structure of functional nanocarbons by means of charge transfer/doping interactions. PMID- 26282305 TI - Combined Ab Initio Computational and Infrared Spectroscopic Study of the cis- and trans-Bis(glycinato)copper(II) Complexes in Aqueous Environment. AB - The cis- and trans-bis(glycinato)copper(II) complexes in aqueous solution have been investigated by means of a combined theoretical and experimental approach. The conducted quantum mechanical charge field molecular dynamics (QMCF-MD) studies, being the first quantum mechanical simulations of organometallic complexes by this method, yielded accurate structural details of the investigated isomers as well as novel dynamic data, which has successfully been confirmed and extended by subsequent mid-infrared measurements. The spectroscopic results, critically assessed by adjacent multivariate data analysis, indicate an isomeric stability at ambient conditions, vanishing at elevated temperatures. PMID- 26282306 TI - When and Why Like-Sized, Oppositely Charged Particles Assemble into Diamond-like Crystals. AB - Like-sized, oppositely charged nanoparticles are known to assemble into large crystals with diamond-like (ZnS) ordering, in sharp contrast to analogous molecular ions and micrometer-scale colloids, which invariably favor more closely packed structures (NaCl or CsCl). Here, we show that these experimental observations can be understood as a consequence of ionic screening and the slight asymmetry in surface charge present on the assembling particles. With this asymmetry taken into account, free-energy calculations predict that the diamond like ZnS lattice is more favorable than other 1:1 ionic structures, namely, NaCl or CsCl, when the Debye screening length is considerably larger than the particle size. A thermodynamic model describes how the presence of neutralizing counterions within the interstitial regions of the crystal acts to bias the formation of low-volume-fraction structures. The results provide general insights into the self-assembly of non-close-packed structures via electrostatic interactions. PMID- 26282307 TI - In Situ Studies of the Temperature-Dependent Surface Structure and Chemistry of Single-Crystalline (001)-Oriented La0.8Sr0.2CoO3-delta Perovskite Thin Films. AB - Perovskites are used to promote the kinetics of oxygen electrocatalysis in solid oxide fuel cells and oxygen permeation membranes. Little is known about the surface structure and chemistry of perovskites at high temperatures and partial oxygen pressures. Combining in situ X-ray reflectivity (XRR) and in situ ambient pressure X-ray photoelectron spectroscopy (APXPS), we report, for the first time, the evolution of the surface structure and chemistry of (001)-oriented perovskite La0.8Sr0.2CoO3-delta (LSC113) and (La0.5Sr0.5)2CoO4+delta (LSC214)-decorated LSC113 (LSC113/214) thin films as a function of temperature. Heating the (001) oriented LSC113 surface leads to the formation of surface LSC214-like particles, which is further confirmed by ex situ Auger electron spectroscopy (AES). In contrast, the LSC113/214 surface, with activities much higher than that of LSC113, is stable upon heating. Combined in situ XRR and APXPS measurements support that Sr enrichment may occur at the LSC113 and LSC214 interface, which can be responsible for its markedly enhanced activities. PMID- 26282308 TI - Effect of Organic and Inorganic Passivation in Quantum-Dot-Sensitized Solar Cells. AB - The effect of semiconductor passivation on quantum-dot-sensitized solar cells (QDSCs) has been systematically characterized for CdS and CdS/ZnS. We have found that passivation strongly depends on the passivation agent, obtaining an enhancement of the solar cell efficiency for compounds containing amine and thiol groups and, in contrast, a decrease in performance for passivating agents with acid groups. Passivation can induce a change in the position of TiO2 conduction band and also in the recombination rate and nature, reflected in a change in the beta parameter. Especially interesting is the finding that beta, and consequently the fill factor can be increased with the passivation treatment. Applying this strategy, record cells of 4.65% efficiency for PbS-based QDSCs have been produced. PMID- 26282309 TI - Quantitative Measurement of Local Infrared Absorption and Dielectric Function with Tip-Enhanced Near-Field Microscopy. AB - Scattering-type scanning near-field optical microscopy (s-SNOM) and Fourier transform infrared nanospectroscopy (nano-FTIR) are emerging tools for nanoscale chemical material identification. Here, we push s-SNOM and nano-FTIR one important step further by enabling them to quantitatively measure local dielectric constants and infrared absorption. Our technique is based on an analytical model, which allows for a simple inversion of the near-field scattering problem. It yields the dielectric permittivity and absorption of samples with 2 orders of magnitude improved spatial resolution compared to far field measurements and is applicable to a large class of samples including polymers and biological matter. We verify the capabilities by determining the local dielectric permittivity of a PMMA film from nano-FTIR measurements, which is in excellent agreement with far-field ellipsometric data. We further obtain local infrared absorption spectra with unprecedented accuracy in peak position and shape, which is the key to quantitative chemometrics on the nanometer scale. PMID- 26282310 TI - Effect of Different Hole Transport Materials on Recombination in CH3NH3PbI3 Perovskite-Sensitized Mesoscopic Solar Cells. AB - We report on perovskite (CH3NH3)PbI3-sensitized solid-state solar cells using spiro-OMeTAD, poly(3-hexylthiophene-2,5-diyl) (P3HT) and 4 (diethylamino)benzaldehyde diphenylhydrazone (DEH) as hole transport materials (HTMs) with a light to electricity power conversion efficiency of 8.5%, 4.5%, and 1.6%, respectively, under AM 1.5G illumination of 1000 W/m(2) intensity. Photoinduced absorption spectroscopy (PIA) shows that hole transfer occurs from the (CH3NH3)PbI3 to HTMs after excitation of (CH3NH3)PbI3. The electron lifetime (taue) in these devices are in the order Spiro-OMeTAD > P3HT > DEH, while the charge transport time (ttr) is rather similar. The difference in taue can therefore explain the lower efficiency of the devices based on P3HT and DEH. This report shows that the nature of the HTM is essential for charge recombination and elucidates that finding an optimal HTM for the perovskite solar cell includes controlling the perovskite/HTM interaction. Design routes for new HTMs are suggested. PMID- 26282311 TI - Factors Controlling the Reactivity of Catalytically Active Monolayers on Metal Substrates. AB - The focus of this work is on the Pt/MS structures (MS = Au, Ir, Ru, or Pt substrate), as promising electrocatalysts and a prototype for more general systems: (active element monolayer)/(metal substrate) (AE/MS). We evaluate from first principles the effects of AE monolayer strain and the interlayer AE-MS electronic state hybridization on surface reactivity and reveal rationale for the interlayer hybridization to dominate over the strain effect in determining the AE/MS surface reactivity. We find, however, that, if AE is weakly bound to MS, the surface electronic structure does not suffice to characterize the surface reactivity, because of involvement of other factors related to lattice response to adsorption of a reaction intermediate. Guided by our findings, we trace surface reactivity to a newly introduced hybridization parameter that reflects important features of the electronic structure of the AE/MS surface, which are not taken into account in the original d-band center model. PMID- 26282312 TI - Different Plasmon Sensing Behavior of Silver and Gold Nanorods. AB - Silver nanorods (AgNRs) of ~20 nm diameter and different lengths, which were increased up to ~100 nm by increasing the reduction time, were prepared by a seedless synthetic approach. A linear relationship between the AgNRs aspect ratios and the LSPR peak position was observed experimentally and confirmed theoretically. The Raman signal enhancement by silver nanorods is more efficient than by gold nanorods (AuNRs) because the plasmon field intensity of AgNRs is stronger than that of AuNRs, as shown by the discrete dipole approximation calculation. The Rayleigh scattering by AuNRs is stronger than that by the AgNRs. Therefore, AuNRs are recommended for optical plasmon imaging, while AgNRs are more efficient in plasmon sensing. PMID- 26282313 TI - Temperature- and Light-Induced Spin Crossover Observed by X-ray Spectroscopy on Isolated Fe(II) Complexes on Gold. AB - Using X-ray absorption techniques, we show that temperature- and light-induced spin crossover properties are conserved for a submonolayer of the [Fe(H2B(pz)2)2(2,2'-bipy)] complex evaporated onto a Au(111) surface. For a significant fraction of the molecules, we see changes in the absorption at the L2,3 edges that are consistent with those observed in bulk and thick film references. Assignment of these changes to spin crossover is further supported by multiplet calculations to simulate the X-ray absorption spectra. As others have observed in experiments on monolayer coverages, we find that many molecules in our submonolayer system remain pinned in one of the two spin states. Our results clearly demonstrate that temperature- and light-induced spin crossover is possible for isolated molecules on surfaces but that interactions with the surface may play a key role in determining when this can occur. PMID- 26282314 TI - New Protocols for the Synthesis of Stable Ag and Au Nanocluster Molecules. AB - "Catching" metals in the nonmetallic form in solution, as they grow to bulk, is one of the most exciting areas of contemporary materials research. A new kind of stabilization to catch the nonmetallic form of noble metals with small thiols has evolved as an exciting area of synthesis during the past decade. Gold clusters stay in the frontline of this research, yielding new "molecules" composed of a few to several hundreds of atoms. By taking guidelines from gold cluster research, various new protocols for silver nanoclusters were developed. In this Perspective, we highlight the recent advances on the synthesis of atomically precise silver, gold, and their alloy clusters with a special emphasis on silver. As a result of intense efforts of the recent past, clusters such as Ag7,8(SR)7,8, Ag7(-S-R-S-)4, Ag9(SR)7, Ag32(SR)19, Ag44(SR)30, Ag140(SR)53, Ag280(SR)140, and Ag152(SR)60 (SR and S-R-S refer to thiolate and dithiolate ligands, respectively) were added to the literature. Moreover, "silver-covered" and "gold-covered" alloy clusters have also been synthesized. Early reports of the crystallization of such clusters are available. Several of these clusters are shown to act as sensors, catalysts, and pesticide degradation agents, which suggests that these materials may find applications in daily life in the foreseeable future. PMID- 26282315 TI - Hybrid Titania Photoanodes with a Nanostructured Multi-Layer Configuration for Highly Efficient Dye-Sensitized Solar Cells. AB - To construct a hybrid titania photoanode containing nanoparticles and nanorods of varied size in a multilayer (ML) configuration for dye-sensitized solar cells, the essence of our ML design is a bilayer system with additional layers of nanorods of well-controlled size inserted between the transparent and the scattering layers to enhance the light-harvesting capability for photosensitizers with small absorptivity, such as Z907. We measured charge-extraction and intensity-modulated photoelectric spectra to show the advantages of one dimensional nanorods with an improved electron-transport property and an upward shift of the potential band edge; a favorable ML configuration was constructed to have a cascade potential feature for feasible electron transport from long nanorods, to normal nanorods, to small nanoparticles. On the basis of the ML system reported herein, we demonstrate how the performance of a Z907 device is improved to attain eta ~10%, which is a milestone for its future commercialization. PMID- 26282316 TI - How to Make Your Next Paper Scientifically Effective. PMID- 26282317 TI - Preparation, regulation and biological application of a Schiff base fluorescence probe. AB - A facile fluorescence switch with Schiff base units was designed and achieved by nucleophilic addition and dehydration reaction. The fluorescence of the probe can be regulated by metal ions (Al(3+) and Cu(2+)). The whole process shows that the weak fluorescence of the probe enhances with the addition of Al(3+), and then the strong fluorescence of the probe/Al(3+) ensemble reduces by introducing Cu(2+). Meanwhile, the solution color changes of the probe with metal ions can be observed under 365 nm UV-vis light from weak light, pale green, green, pale green to weak light. Noticeably, the photo regulation processes of the probe by metal ions can be realized in the biological system and applied in cells imaging. The work provides a new strategy for designing facile regulation probe and develops a new application for Schiff base derivatives. PMID- 26282318 TI - Computational insights into the molecular interaction and ion-pair structures of a novel zinc-functionalized ionic liquid, [Emim][Zn(TFSI)3]. AB - The ion pair structures of a novel CO2 capture material in the form of a metal chelate anion-containing room temperature ionic liquid (IL), 1-ethyl-3 methylimidazolium tri[bis(trifluoromethylsulfonyl)imide]zincate(II), [Emim][Zn(TFSI)3], were elucidated by correlating the infrared spectra generated using density functional theory (DFT) calculations with the experimental spectrum derived from a room temperature infrared spectroscopic measurement. A free volume energy minimization algorithm revealed stable structures where the zinc ion forms an octahedral, homoleptic complex with the ligand bis(trifluoromethylsulfonyl)imide through coordination with the oxygen of the sulfone group, with 1-ethyl-3-methylimidazolium acting as the counterion. The method of analysis was built around 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [Emim][TFSI], involving direct comparison with published data, and extended to the more complex [Emim][Zn(TFSI)3] system. The DFT calculations reproduced the vibrational spectra of [Emim][Zn(TFSI)3] and [Emim][TFSI] using their optimized geometries, with correlation slopes of 0.9996 and 1.0022, respectively. Comparison of the vibrational modes of [Emim][TFSI] and [Emim][Zn(TFSI)3] provided insights into the ion pair structure of, and molecular interactions in the ILs analyzed. PMID- 26282319 TI - Unidirectional growth of large size urea doped L-cysteine hydrochloride monohydrate NLO organic crystal and investigations of its crystalline and optical properties. AB - Organic crystals of urea doped L-cysteine hydrochloride monohydrate have been grown by unidirectional solution growth technique. The crystal grown by this technique has high growth rate as compared to the crystals grown using conventional slow cooling method. This method is ideally suited to grow crystals along a specific direction. The growth process was monitored at regular intervals of time in a time-lapsed manner to estimate the growth rate and also monitor its quality visually. The grown crystal was subjected to different characterizations in order to confirm the phase of the grown crystal, its crystalline perfection and optical properties. The X-ray diffraction confirmed the phase of the crystal. The rocking curve recorded using high resolution X-ray diffraction (HRXRD) technique reveals that the crystal grown using conventional slow cooling method has internal gain boundaries whereas that grown by unidirectional technique has high degree of crystalline perfection. The bonding environment present in the crystal was characterized by FTIR spectroscopy where vibrational frequencies of the different functional groups present were identified. The optical quality of the crystal was characterized using UV-vis-NIR spectrophotometer and Mach-Zehnder interferometer. The nonlinear optical response of the crystal was measured using Kurtz-Perry method and found to be 1.4 times that of a KDP crystal. PMID- 26282320 TI - Spectroscopic studies of porphyrin functionalized multiwalled carbon nanotubes and their interaction with TiO2 nanoparticles surface. AB - UV-vis and fluorescence investigations about the non-covalent interaction, in ethanolic solutions, of multi-wall carbon nanotube (MWCNT) with Coproporphyrin-I, and its Cu(II) and Zn(II) complexes (MCPIs) have been reported. Evidence of binding between MWCNTs and porphyrins was discovered from spectral adsorption decrease with respect to free porphyrins and by the exhibition of photoluminescence quenching with respect to free porphyrins demonstrating that MWCNT@MCPIs are potential donor-acceptor complexes. Equilibrium and kinetic aspects in the interactions with monolayer transparent TiO2 thin films with the obtained MWCNT@MCPIs are clarified showing their effective adsorption by porphyrin links on the TiO2 monolayer support, with respect to not only MWCNTs, according to the Langmuir model and with pseudo-first-order kinetics. Morphological description of the adsorption of MWCNT@MCPIs on TiO2 with scanning electron microscopy has been reported. The obtained experimental evidences describe therefore MWCNT@MCPIs as potential sensitizers in the DSSC (Dye Sensitized Solar Cell) applications. PMID- 26282321 TI - Accurate predictions of spectroscopic and molecular properties of 27 Lambda-S and 73 Omega states of AsS radical. AB - The PECs are calculated for the 27 Lambda-S states and their corresponding 73 Omega states of AsS radical. Of these Lambda-S states, only the 2(2)Delta and 5(4)Pi states are replulsive. The 1(2)Sigma(+), 2(2)Sigma(+), 4(2)Pi, 3(4)Delta, 3(4)Sigma(+), and 4(4)Pi states possess double wells. The 3(2)Sigma(+) state possesses three wells. The A(2)Pi, 3(2)Pi, 1(2)Phi, 2(4)Pi, 3(4)Pi, 2(4)Delta, 3(4)Delta, 1(6)Sigma(+), and 1(6)Pi states are inverted with the SO coupling effect included. The 1(4)Sigma(+), 2(4)Sigma(+), 2(4)Sigma(-), 2(4)Delta, 1(4)Phi, 1(6)Sigma(+), and 1(6)Pi states, the second wells of 1(2)Sigma(+), 3(4)Sigma(+), 4(2)Pi, 4(4)Pi, and 3(4)Delta states, and the third well of 3(2)Sigma(+) state are very weakly-bound states. The PECs are extrapolated to the CBS limit. The effect of SO coupling on the PECs is discussed. The spectroscopic parameters are evaluated, and compared with available measurements and other theoretical ones. The vibrational properties of several weakly-bound states are determined. The spectroscopic properties reported here can be expected to be reliably predicted ones. PMID- 26282322 TI - Larger aggregates of mutant seipin in Celia's Encephalopathy, a new protein misfolding neurodegenerative disease. AB - Celia's Encephalopathy (MIM #615924) is a recently discovered fatal neurodegenerative syndrome associated with a new BSCL2 mutation (c.985C>T) that results in an aberrant isoform of seipin (Celia seipin). This mutation is lethal in both homozygosity and compounded heterozygosity with a lipodystrophic BSCL2 mutation, resulting in a progressive encephalopathy with fatal outcomes at ages 6 8. Strikingly, heterozygous carriers are asymptomatic, conflicting with the gain of toxic function attributed to this mutation. Here we report new key insights about the molecular pathogenic mechanism of this new syndrome. Intranuclear inclusions containing mutant seipin were found in brain tissue from a homozygous patient suggesting a pathogenic mechanism similar to other neurodegenerative diseases featuring brain accumulation of aggregated, misfolded proteins. Sucrose gradient distribution showed that mutant seipin forms much larger aggregates as compared with wild type (wt) seipin, indicating an impaired oligomerization. On the other hand, the interaction between wt and Celia seipin confirmed by coimmunoprecipitation (CoIP) assays, together with the identification of mixed oligomers in sucrose gradient fractionation experiments can explain the lack of symptoms in heterozygous carriers. We propose that the increased aggregation and subsequent impaired oligomerization of Celia seipin leads to cell death. In heterozygous carriers, wt seipin might prevent the damage caused by mutant seipin through its sequestration into harmless mixed oligomers. PMID- 26282325 TI - The Psychosomatic Factor in Clinical Practice. 23rd World Congress on Psychosomatic Medicine, Glasgow, August 20-22, 2015: Abstracts. PMID- 26282323 TI - Mitochondria and endoplasmic reticulum crosstalk in amyotrophic lateral sclerosis. AB - Physical and functional interactions between mitochondria and the endoplasmic reticulum (ER) are crucial for cell life. These two organelles are intimately connected and collaborate to essential processes, such as calcium homeostasis and phospholipid biosynthesis. The connections between mitochondria and endoplasmic reticulum occur through structures named mitochondria associated membranes (MAMs), which contain lipid rafts and a large number of proteins, many of which serve multiple functions at different cellular sites. Growing evidence strongly suggests that alterations of ER-mitochondria interactions are involved in neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), a devastating and rapidly fatal motor neuron disease. Mutations in proteins that participate in ER-mitochondria interactions and MAM functions are increasingly being associated with genetic forms of ALS and other neurodegenerative diseases. This evidence strongly suggests that, rather than considering the two organelles separately, a better understanding of the disease process can derive from studying the alterations in their crosstalk. In this review we discuss normal and pathological ER-mitochondria interactions and the evidence that link them to ALS. PMID- 26282326 TI - Lack of agreement between computer navigation and post-operative 2-dimensional computed tomography (CT) measurements for component and limb alignment in total knee arthroplasty (TKA). AB - BACKGROUND: The purpose of this study was to assess the degree of mismatch between intraoperative navigation data using imageless computer navigation and post-operative CT scan measurements with respect to bone cuts, component and limb alignment during TKA. METHODS: Intraoperative navigation data including bone cut verification and overall limb alignment during TKA was compared to postoperative CT measurements of component and limb alignment according to the Perth protocol. The proportion of cases with mismatch between navigation and CT measurements at two and three degree thresholds was identified. RESULTS: In a total sample of 50 primary TKAs, 20% of cases showed a mismatch of more than two degrees between navigation and CT obtained measurements for coronal femoral alignment, 42% for femoral rotation, 16% for tibial component coronal alignment and 32% for overall limb alignment. CONCLUSION: Mismatch between intraoperative navigation data and postoperative CT measurements suggests that postoperative CT scan alignment data should be interpreted with caution. A surgeon should consider a multitude of factors when analysing component and limb alignment postoperatively. PMID- 26282324 TI - Selective reduction of striatal mature BDNF without induction of proBDNF in the zQ175 mouse model of Huntington's disease. AB - Huntington's disease (HD) is a neurodegenerative disorder characterized by massive loss of medium spiny neurons in the striatum. However, the mechanisms by which mutant huntingtin leads to this selective neuronal death remain incompletely understood. Brain-derived neurotrophic factor (BDNF) has been shown to be neuroprotective on HD striatal neurons both in vitro and in vivo. ProBDNF, the precursor of mature BDNF (mBDNF), also can be secreted but promotes apoptosis of neurons expressing p75(NTR) and sortilin receptors. Although a reduction of total striatal BDNF protein has been reported in HD patients and mouse models, it remains unclear whether conversion of proBDNF to mBDNF is altered in HD, and whether the proBDNF receptors, p75(NTR) and sortilin are dysregulated, leading to impaired striatal neuron survival. To test these hypotheses, we generated bdnf-HA knock-in (KI) mice on the zQ175 HD background to accurately quantitate the levels of both proBDNF and mBDNF in the HD striatum. In aged zQ175 HD mice, we observed a significant loss of mBDNF and decreased TrkB activation, but no increase of proBDNF or p75(NTR) levels either in the sensorimotor cortex or the striatum. However, immunoreactivities of p75(NTR) and sortilin receptor are both increased in immature striatal oligodendrocytes, which associate with significant myelin defects in the HD striatum. Taken together, the present study indicates that diminished mature BDNF trophic signaling through the TrkB receptor, rather than an induction in proBDNF, is a main contributing factor to the vulnerability of striatal neurons in the zQ175 HD mouse model. PMID- 26282327 TI - Third Report on Chicken Genes and Chromosomes 2015. PMID- 26282329 TI - Properties of human immunodeficiency virus type 1 reverse transcriptase recombination upon infection. AB - Reverse transcription (RT) is one of the hallmark features of retroviruses. During RT, virus encoded reverse transcriptase (RTase) must transfer from one end to the other end of the viral genome on two separate occasions to complete RT and move on to the production of proviral DNA. In addition, multiple strand-transfer events between homologous regions of the dimerized viral genome by RTase are also observed, and such recombination events serve as one of the driving forces behind human immunodeficiency virus (HIV) genome sequence diversity. Although retroviral recombination is widely considered to be important, several features of its mechanism are still unclear. We constructed an HIV-1 vector system to examine the target sequences required for virus recombination, and elucidated other necessary prerequisites to harbor recombination, such as the length, homology and the stability of neighbouring structures around the target sequences. PMID- 26282328 TI - Single-voxel (1)H spectroscopy in the human hippocampus at 3 T using the LASER sequence: characterization of neurochemical profile and reproducibility. AB - The hippocampus is crucial for long-term episodic memory and learning. It undergoes structural change in aging and is sensitive to neurodegenerative and psychiatric diseases. MRS studies have seldom been performed in the hippocampus due to technical challenges. The reproducibility of MRS in the hippocampus has not been evaluated at 3 T. The purpose of the present study was to quantify the concentration of metabolites in a small voxel placed in the hippocampus and evaluate the reproducibility of the quantification. Spectra were measured in a 2.4 mL voxel placed in the left hippocampus covering the body and most of the tail of the structure in 10 healthy subjects across three different sessions and quantified using LCModel. High-quality spectra were obtained, which allowed a reliable quantification of 10 metabolites including glutamate and glutamine. Reproducibility of MRS was evaluated with coefficient of variation, standard errors of measurement, and intraclass correlation coefficients. All of these measures showed improvement with increased number of averages. Changes of less than 5% in concentration of N-acetylaspartate, choline-containing compounds, and total creatine and of less than 10% in concentration of myo-inositol and the sum of glutamate and glutamine can be confidently detected between two measurements in a group of 20 subjects. A reliable and reproducible neurochemical profile of the human hippocampus was obtained using MRS at 3 T in a small hippocampal volume. PMID- 26282330 TI - The role of haplotype in 15q25.1 locus in lung cancer risk: results of scanning chromosome 15. AB - The role of haplotypes and the interaction of haplotypes and smoking in lung cancer risk have not been well characterized. We analyzed data from an Italian population-based, case-control study with 1815 lung cancer patients and 1959 healthy controls in discovery, and performed a validation using a case-control study with 2983 lung cancer patients and 3553 healthy controls of European ancestry for replication. Sliding window haplotype analysis within chromosome 15, evaluating 4722250 haplotypes and pair-wise haplotype analysis identified that CHRNA5 rs588765-rs16969968 was the most significant haplotype associated with lung cancer risk (omnibus P = 8.35*10(-15) in discovery and 7.26*10(-14) in replication), and improved the prediction of case status over that provided by the individual SNPs rs16969968 or rs588765 (likelihood ratio test P = 0.006 for rs16969968 and 3.83*10(-14) for rs588765 in discovery, 0.009 for rs16969968 and 4.62*10(-13) for rs588765 in replication, compared with rs588765-rs16969968). Compared with the wild-type homozygous diplotype, CA/CA homozygote exhibited an approximately 2-fold increase risk for lung cancer (OR = 2.12; 95% CI 1.46-3.07 in discovery, and OR = 2.01; 95% CI 1.51-2.67 in replication). Even among never smokers, CA/CA homozygote showed an increased risk of lung cancer with borderline significance in discovery (adjusted OR = 1.75, 95% CI 0.96-3.19) and statistical significance in replication (adjusted OR = 2.10, 95% CI 1.12-3.96), compared with combined genotypes (CG/CG + CG/TG). Accordingly, rs588765-rs16969968 may be a genetic marker to lung cancer risk, even among never-smokers. PMID- 26282331 TI - Cross-cultural comparisons between the earthquake preparedness models of Taiwan and New Zealand. AB - Taiwan and New Zealand are both located in the Pacific Rim where 81 per cent of the world's largest earthquakes occur. Effective programmes for increasing people's preparedness for these hazards are essential. This paper tests the applicability of the community engagement theory of hazard preparedness in two distinct cultural contexts. Structural equation modelling analysis provides support for this theory. The paper suggests that the close fit between theory and data that is achieved by excluding trust supports the theoretical prediction that familiarity with a hazard negates the need to trust external sources. The results demonstrate that the hazard preparedness theory is applicable to communities that have previously experienced earthquakes and are therefore familiar with the associated hazards and the need for earthquake preparedness. The paper also argues that cross-cultural comparisons provide opportunities for collaborative research and learning as well as access to a wider range of potential earthquake risk management strategies. PMID- 26282332 TI - Measuring Quality in Ambulatory Orthopedic Surgery. PMID- 26282333 TI - Timing and content of interventions to enhance cognitive performance of very-low birthweight children. PMID- 26282334 TI - Watching your pain site reduces pain intensity in chronic back pain patients. AB - BACKGROUND: Chronic back pain (CBP) is a frequent debilitating and often treatment-resistant disorder. The awareness of one's own body seems to be essential in pain reduction through visual input. Visual feedback of the back reduces experimental pain perception in CBP at this site and watching the back during repeated lumbar spine movements reduces movement-evoked pain. In this study, we tested whether visual feedback alone can reduce habitual pain in CBP. METHODS: In a within-subject design, 19 CBP patients participated in an online visual feedback condition, watching one's own back. This was compared to several control conditions, such as watching a neutral object (book), a video of another person of the same sex, a picture of the own back, and keeping one's eyes closed in randomized order on five separate days. In each experimental session, participants rated habitual pain intensity and unpleasantness before and after the experimental manipulation. RESULTS: We present evidence that visual feedback by watching the site of chronic pain on a video screen alone is sufficient to reduce habitual chronic pain. No additional manipulation or movement was necessary. CONCLUSIONS: These results suggest that online video feedback may be helpful in alleviating chronic pain. PMID- 26282335 TI - Predicting growth and mortality of bivalve larvae using gene expression and supervised machine learning. AB - It is commonly known that the nature of the diet has diverse consequences on larval performance and longevity, however it is still unclear which genes have critical impacts on bivalve development and which pathways are of particular importance in their vulnerability or resistance. First we show that a diet deficient in essential fatty acid (EFA) produces higher larval mortality rates, a reduced shell growth, and lower postlarval performance, all of which are positively correlated with a decline in arachidonic and eicosapentaenoic acids levels, two EFAs known as eicosanoid precursors. Eicosanoids affect the cell inflammatory reactions and are synthesized from long-chain EFAs. Second, we show for the first time that a deficiency in eicosanoid precursors is associated with a network of 29 genes. Their differential regulation can lead to slower growth and higher mortality of Mytilus edulis larvae. Some of these genes are specific to bivalves and others are implicated at the same time in lipid metabolism and defense. Several genes are expressed only during pre-metamorphosis where they are essential for muscle or neurone development and biomineralization, but only in stress-induced larvae. Finally, we discuss how our networks of differentially expressed genes might dynamically alter the development of marine bivalves, especially under dietary influence. PMID- 26282337 TI - Case of syringomatous carcinoma: Positive immunohistochemical staining of c-KIT and phosphorylated-extracellular signal-regulated kinase 1/2. PMID- 26282336 TI - A naturalistic examination of the temporal patterns of affect and eating disorder behaviors in anorexia nervosa. AB - OBJECTIVE: Evidence supports the presence of significant variability in the timing of affective experiences and eating disorder (ED) behaviors across ED populations. This study examined the naturalistic timing of affective states and ED behaviors in anorexia nervosa (AN). METHODS: Women (N = 118) with full or subthreshold DSM-IV AN completed 2 weeks of ecological momentary assessment (EMA) involving self-reports of affect and ED behaviors. Patterns of positive affect, negative affect, and tension/anxiety across hours of the day and days of the week were examined using linear mixed models. Variation in ED behavior occurrence (i.e., binge eating, vomiting, exercise, meal skipping, and self-weighing) across hours of the day and days of the week was examined using general estimating equations. RESULTS: Results revealed significant variation in tension/anxiety across hours of the day; there were no significant associations between time of day and negative or positive affect. All affective variables significantly varied across days of the week, with both negative affect and tension/anxiety highest in the middle of the week and lowest on the weekends. The ED behaviors all significantly varied across hours of the day, with binge eating and vomiting most common in later hours, exercise and self-weighing most common in earlier hours, and meal skipping most common at times corresponding to breakfast and lunch. ED behaviors did not significantly vary across days of the week. CONCLUSION: The significant patterns of variation in the timing of affective experiences and ED behaviors may have utility in informing theories and interventions for AN. PMID- 26282338 TI - Nitrogen-Enriched Fe3O4@Carbon Nanospheres Derived from Fe3O4@3 Aminophenol/Formaldehyde Resin Nanospheres Based on a Facile Hydrothermal Strategy: Towards a Robust Catalyst Scaffold for Platinum Nanocrystals. AB - Robust nitrogen-enriched Fe3O4@carbon nanospheres have been fabricated as a catalyst scaffold for Pt nanoparticles. In this work, core-shell Fe3O4@3 aminophenol/formaldehyde (APF) nanocomposites were first synthesized by a simple hydrothermal method, and subsequently carbonized to Fe3O4@N-Carbon nanospheres for in situ growth of Pt nanocrystals. Abundant amine groups were distributed uniformly onto Fe3O4@N-Carbon nanospheres, which not only improved the dispersity and stability of the Pt nanocrystals, but also endowed the Pt-based catalysts with good compatibility in organic solvents. The dense three-dimensional cross linked carbon shell protects the Fe3O4 cores against damage from harsh chemical environments, even in aqueous HCl (up to 1.0 M) or NaOH (up to 1.0 M) solutions under ultrasonication for 24 hours, which indicates that it can be used as a robust catalyst scaffold. In the reduction of nitrobenzene compounds, the Fe3O4@N Carbon@Pt nanocatalysts show outstanding catalytic activity, stability, and recoverability. PMID- 26282339 TI - Factors associated with illicit methadone injecting in a Canadian setting. AB - BACKGROUND AND OBJECTIVES: While methadone is well established as an evidence based treatment for opioid use disorder, safety concerns persist regarding its diversion. The authors examine the prevalence of and risk factors associated with injection of methadone in an urban population. METHODS: Between December 2005 and November 2013, data were derived from two open prospective studies of persons who inject drugs (PWID) in Vancouver, Canada. Generalized estimating equations (GEE) logistic regression was used to determine factors independently associated with illicit methadone injecting. RESULTS: During the study, 1911 individuals (34% women) were recruited; 134 (7%) participants reported methadone injecting at least once. In multivariable analysis, Caucasian ethnicity [adjusted odds ratio (AOR) = 1.90, 95% confidence interval (CI) = 1.20-3.00]; homelessness (AOR = 1.46, 95% CI = 1.09-1.95); drug dealing (AOR = 2.10, 95% CI = 1.50-2.93); >=daily heroin injection (AOR = 1.57, 95% CI = 1.08-2.26); >=daily crack smoking (AOR = 2.06, 95% CI = 1.44-2.95); being a victim of violence (AOR = 1.48, 95% CI = 1.04 2.12); and non-fatal overdose (AOR = 1.67, 95% CI = 1.67 (1.00-2.79) were independently and positively associated with methadone injection; female gender (AOR = 0.47, 95% CI = 0.30-0.75) was negatively associated. DISCUSSION AND CONCLUSIONS: The diversion of methadone for illicit injection in this urban setting was associated with several markers of addiction severity and other health and social vulnerabilities. SCIENTIFIC SIGNIFICANCE: These findings underscore the need to ensure methadone accessibility while limiting diversion related risk. PMID- 26282340 TI - Introduction to the diagnosis and classification of monocytic-lineage leukemias by flow cytometry. AB - Despite diagnostic criteria are currently available for the distinct subtypes of monocytic-lineage neoplasias, a number of partially overlapping features still remain evident, which may hamper their differential diagnosis. An accurate identification and characterization of monocytic cells is of major relevance for the diagnosis and classification of these neoplasias. In this regard, as compared to other conventional techniques, flow cytometry has shown the highest sensitivity for detection of early monocytic commitment of (normal and neoplastic) bone marrow CD34+ hematopoietic precursors as well as of monocytic aberrations and maturation blockades, which are frequently associated with clonal myeloid disorders. In the present paper we provide basic principles and criteria for multiparameter flow cytometry identification and characterization of bone marrow monocytic cells that contribute to an improved diagnostic and classification of monocytic lineage-associated acute leukemias in clinical settings, particularly when using the EuroFlow antibody panels. (c) 2015 International Clinical Cytometry Society. PMID- 26282341 TI - Facing the environment: onset and development of UV markings in young fish. AB - Most colour patterns in animals represent an elegant compromise between conspicuousness to ensure effective communication with preferred receivers and camouflage to avoid attracting the attention of unwanted predators. Many species, including several coral reef fishes, overcome this conflict by using ultraviolet (UV) colouration and signalling, as these colours are visible only over short distances and are often invisible to their predators. Despite a great interest in their behavioural significance and ecological influence on survival, little is known about when these colours first develop on the bodies of free-living animals. Here we show for the first time that the UV facial patterns of a coral reef fish do not develop in captivity but only when juveniles experience the socio-behavioural conditions of their natural environment. Using field and laboratory experiments, we determined that the onset and early development of these UV facial markings did not occur at metamorphosis. Instead, juveniles developed the UV markings during their first two weeks on the reef. Exposure to different reef environments revealed significant plasticity in the development of these markings. The direct or indirect (through intraspecific interactions) exposure to predators is a likely candidate trigger for the plastic development of these UV markings in the wild. PMID- 26282343 TI - Effects of strength training on muscle cellular outcomes in prostate cancer patients on androgen deprivation therapy. AB - Androgen deprivation therapy (ADT) improves life expectancy in prostate cancer (PCa) patients, but is associated with adverse effects on muscle mass. Here, we investigated the effects of strength training during ADT on muscle fiber cross sectional area (CSA) and regulators of muscle mass. PCa patients on ADT were randomized to 16 weeks of strength training (STG) (n = 12) or a control group (CG; n = 11). Muscle biopsies were obtained from m. vastus lateralis and analyzed by immunohistochemistry and western blot. Muscle fiber CSA increased with strength training (898 MUm(2) , P = 0.04), with the only significant increase observed in type II fibers (1076 MUm(2) , P = 0.03). There was a trend toward a difference in mean change between groups myonuclei number (0.33 nuclei/fiber, P = 0.06), with the only significant increase observed in type I fibers, which decreased the myonuclear domain size of type I fibers (P = 0.05). Satellite cell numbers and the content of androgen receptor and myostatin remained unchanged. Sixteen weeks of strength training during ADT increased type II fiber CSA and reduced myonuclear domain in type I fibers in PCa patients. The increased number of satellite cells normally seen following strength training was not observed. PMID- 26282342 TI - Identification of critical functional determinants of kainate receptor modulation by auxiliary protein Neto2. AB - KEY POINTS: Kainate receptors (KARs) are ionotropic glutamate receptors (iGluRs) that modulate synaptic transmission and intrinsic neuronal excitability. KARs associate with the auxiliary proteins neuropilin- and tolloid-like 1 and 2 (Neto1 and Neto2), which act as allosteric modulators of receptor function impacting all biophysical properties of these receptors studied to date. M3-S2 linkers play a critical role in KAR gating; we found that individual residues in these linkers bidirectionally influence Neto2 modulation of KAR desensitization in an agonist specific manner. We also identify the D1 dimer interface as a novel site of Neto2 modulation and functionally correlate the actions of Neto2 modulation of desensitization with modulation of cation sensitivity. We identify these domains as determinants of Neto2 modulation. Thus, our work contributes to the understanding of auxiliary subunit modulation of KAR function and could aid the development of KAR-specific modulators to alter receptor function. ABSTRACT: Kainate receptors (KARs) are important modulators of synaptic transmission and intrinsic neuronal excitability in the CNS. Their activity is shaped by the auxiliary proteins Neto1 and Neto2, which impact KAR gating in a receptor subunit and Neto isoform-specific manner. The structural basis for Neto modulation of KAR gating is unknown. Here we identify the M3-S2 gating linker as a critical determinant contributing to Neto2 modulation of KARs. M3-S2 linkers control both the valence and magnitude of Neto2 modulation of homomeric GluK2 receptors. Furthermore, a single mutation in this domain abolishes Neto2 modulation of heteromeric receptor desensitization. Additionally, we found that cation sensitivity of KAR gating is altered by Neto2 association, suggesting that stability of the D1 dimer interface in the ligand-binding domain (LBD) is an important determinant of Neto2 actions. Moreover, modulation of cation sensitivity was eliminated by mutations in the M3-S2 linkers, thereby correlating the action of Neto2 at these structurally discrete sites on receptor subunits. These results demonstrate that the KAR M3-S2 linkers and LBD dimer interface are critical determinants for Neto2 modulation of receptor function and identify these domains as potential sites of action for the targeted development of KAR specific modulators that alter the function of auxiliary proteins in native receptors. PMID- 26282344 TI - Effect of Low-Density Lipoprotein Cholesterol Lowering by Ezetimibe/Simvastatin on Outcome Incidence: Overview, Meta-Analyses, and Meta-Regression Analyses of Randomized Trials. AB - This analysis investigated the extent of different outcome reductions from low density lipoprotein cholesterol (LDL-C) lowering following ezetimibe/simvastatin treatment and the proportionality of outcome to LDL-C reductions. The authors searched PubMed between 1997 and mid-June 2015 (any language) and the Cochrane Library to identify all randomized controlled trials comparing ezetimibe/simvastatin with placebo or less intensive LDL-C lowering. Risk ratios (RR) and 95% confidence intervals (CIs), standardized to 20 mg/dL LDL-C reduction, were calculated for 5 primary outcomes (fatal and nonfatal) and 4 secondary outcomes (non-cardiovascular [CV] death, cancer, myopathy, and hepatopathy). Five ezetimibe/simvastatin RCTs (30 051 individuals) were eligible, 2 comparing ezetimibe/simvastatin vs placebo and 3 vs less intensive treatment. Outcomes reduced almost to the same extent were stroke (RR: -13%, 95% CI: -21% to -3%), coronary heart disease (CHD; RR: -12%, 95% CI: -19% to -5%), and composite of stroke and CHD (RR: -14%, 95% CI: -20% to -8%). Absolute risk reductions: 5 strokes, 10 CHD events, and 16 stroke and CHD events prevented for every 1000 patients treated for 5 years. Residual risk was almost 7* higher than absolute risk reduction for all the above outcomes. All death outcomes were not reduced, and secondary outcomes did not differ between groups. Logarithmic risk ratios were not associated with LDL-C lowering. Our meta-analysis provides evidence that, in patients with different CV disease burden, major CV events are safely reduced by LDL-C lowering with ezetimibe/simvastatin, while raising the hypothesis that the extent of LDL-C lowering might not be accompanied by incremental clinical-event reduction. PMID- 26282345 TI - Consumption of and satisfaction with health care among opioid users with chronic non-malignant pain. PMID- 26282347 TI - Premature Ventricular Complexes and Premature Ventricular Complex Induced Cardiomyopathy. AB - Presentation, prognosis, and management of premature ventricular complexes (PVCs) vary significantly among patients and depend on PVC characteristics as well as patient comorbidities. Presentation can range from incidental discovery in an asymptomatic patient to debilitating heart failure. Prognosis depends on, among other factors, the presence or absence of structural heart disease, PVC burden and other factors detailed in this review. Our understanding of the clinical significance of frequent PVCs, particularly as it relates to development of cardiomyopathy, has advanced greatly in the past decade. In this article, we explore the mechanisms governing PVC initiation and discuss prevalence and frequency of PVCs in the general population. We also explore prognostic implications based on PVC frequency as well as the presence or absence of underlying heart disease. We then take a focused look at PVC-induced cardiomyopathy and identify predictors for developing cardiomyopathy. Finally, we discuss clinical evaluation and management of patients presenting with frequent PVCs. Management can include clinical observation, addressing reversible causes, lifestyle modification, pharmacotherapy, or catheter ablation. PMID- 26282348 TI - CysLT2 receptor mediates lipopolysaccharide-induced microglial inflammation and consequent neurotoxicity in vitro. AB - Neuroinflammation induced by microglial activation plays a critical role in many neurodegenerative diseases, including Parkinson's disease (PD). Recent studies have indicated that cysteinyl leukotriene receptor 2 (CysLT2R) is involved in inflammation and brain injury after cerebral ischemia. However, the role of CysLT2R in microglial responses associated with PD remains unclear. In the present study, we determined the regulatory roles of CysLT2R in microglial inflammation and subsequent neurotoxicity in an in vitro brain inflammation model induced by the microglial activator lipopolysaccharide (LPS). We found that LPS induced phagocytosis of a murine microglial cell line (BV-2 cells) and increased production of the proinflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1beta (IL-1beta). The expression of CysLT2R protein was up-regulated and the nuclear translocation of CysLT2R was induced in LPS-activated BV-2 cells. CysLT2R selective antagonist HAMI 3379 significantly inhibited LPS-induced phagocytosis and overproduction of the cytokines in BV-2 cells. Similarly, the CysLT2R silencing by specific short hairpin RNA (shRNA) had the same effects as those of HAMI 3379, suggesting that the effect might be CysLT2R-dependent. Furthermore, the conditioned medium (CM) derived from LPS-treated BV-2 cells induced the cell death of a rat adrenal pheochromocytoma cell line (PC12). HAMI 3379 and CysLT2R shRNA attenuated neuronal death by suppressing the production of neurotoxic cytokines released from LPS-activated microglia. Collectively, these results suggest that CysLT2R mediates LPS-induced microglial inflammation and consequent neurotoxicity. CysLT2R may be a promising molecular target that modulates microglia-related neuroinflammation in neurodegenerative disorders, such as PD. PMID- 26282349 TI - The mature/pro nerve growth factor ratio is decreased in the brain of diabetic rats: Analysis by ELISA methods. AB - Nerve growth factor (NGF) is essential for the survival and functional maintenance of forebrain cholinergic neurons projecting mainly to the cortex and hippocampus. NGF is produced in these brain areas but while mature NGF (mNGF) has a survival/differentiative effect its precursor proNGF elicits apoptosis in cholinergic neurons. Impaired neurotransmission, loss of cholinergic phenotype and abnormal NGF content characterize the cholinergic circuitries in animal models of diabetic encephalopathy (DE). It is not known whether defective production or maturation of NGF could play a key role in cholinergic neurodegeneration in DE. Quantification of the mNGF/proNGF ratio is therefore needed to characterize the development and progression of NGF-related neuronal diseases. In our work, we aimed at developing ELISA methods to measure either mNGF or proNGF tissue concentration; and to define the mNGF/proNGF ratio in the rat cortex and hippocampus during the early stage of streptozotocin-induced type 1 diabetes. Using commercially available NGF ELISA kits and antibodies, we set up ELISAs for human and rat mNGF and proNGF. We then analyzed the mNGF/proNGF ratio in the cortex and hippocampus of DE rats and found that it decreased in both tissues starting from the fourth week after diabetes induction. In diabetic brain the increase in proNGF involves accumulation of the isoforms with molecular weights of 50 and 34 kDa. Our study for the first time specifically quantifies the absolute content of mature and proNGF and the mNGF/proNGF ratio in brain tissues, suggesting that early progression of experimental DE is characterized by defective maturation of NGF. PMID- 26282350 TI - ABCG2 transporter inhibitor restores the sensitivity of triple negative breast cancer cells to aminolevulinic acid-mediated photodynamic therapy. AB - Photosensitizer protoporphyrin IX (PpIX) fluorescence, intracellular localization and cell response to photodynamic therapy (PDT) were analyzed in MCF10A normal breast epithelial cells and a panel of human breast cancer cells including estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) positive and triple negative breast cancer (TNBC) cells after treatment with PpIX precursor aminolevulinic acid (ALA). Although PpIX fluorescence was heterogeneous in different cells, TNBC cells showed significantly lower PpIX level than MCF10A and ER- or HER2-positive cells. PpIX fluorescence in TNBC cells also had much less mitochondrial localization than other cells. There was an inverse correlation between PpIX fluorescence and cell viability after PDT. Breast cancer cells with the highest PpIX fluorescence were the most sensitive to ALA-PDT and TNBC cells with the lowest PpIX level were resistant to PDT. Treatment of TNBC cells with ABCG2 transporter inhibitor Ko143 significantly increased ALA-PpIX fluorescence, enhanced PpIX mitochondrial accumulation and sensitized cancer cells to ALA-PDT. Ko143 treatment had little effect on PpIX production and ALA PDT in normal and ER- or HER2-positive cells. These results demonstrate that enhanced ABCG2 activity renders TNBC cell resistance to ALA-PDT and inhibiting ABCG2 transporter is a promising approach for targeting TNBC with ALA-based modality. PMID- 26282352 TI - Re: comparative analysis of transperineal template saturation prostate biopsy versus magnetic resonance imaging targeted biopsy with magnetic resonance imaging ultrasound fusion guidance. PMID- 26282351 TI - Treatment of Periodontitis for the Prevention of Endothelial Dysfunction: A Narrative Review. AB - Endothelial dysfunction (ED) is the initial step in the development of atherosclerosis, leading to cardiovascular disease (CVD). It has been suggested that periodontal disease (PD) could be associated to pathogenesis of atherosclerosis, since it is able to trigger a host response with systemic inflammation. Although a number of epidemiological studies have shown that periodontitis could be associated with ED, it is still unclear whether periodontal treatment could improve ED and therefore cardiovascular outcomes. In this narrative review we analysed the literature in the databases of Medline under ''endothelial function OR dysfunction OR vasodilatation'', AND ''periodontal disease" OR periodontal treatment" AND "cardiovascular disease" OR atherosclerosis AND "endothelial biomarker". Research articles, systematic reviews and clinical trials were screened. ED could be related to periodontitis as well as to CVD. Periodontal treatment reduces the risk of teeth loss and may improve ED and the risk of CVD. Since controversial results exist, there is an urgent need for well-designed clinical trials to find and validate novel biomarkers of endothelial function, such as circulating endothelial progenitors, which may be crucial for further investigation of the association of PD with endothelial function and CVD. PMID- 26282353 TI - Re: comparison of MR/ultrasound fusion-guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer. PMID- 26282354 TI - Re: nadir testosterone within first year of androgen-deprivation therapy (ADT) predicts for time to castration-resistant progression: a secondary analysis of the PR-7 trial of intermittent versus continuous ADT. PMID- 26282355 TI - Re: effect of bipolar androgen therapy for asymptomatic men with castration resistant prostate cancer: results from a pilot clinical study. PMID- 26282356 TI - Re: renal ischemia and function after partial nephrectomy: a collaborative review of the literature. PMID- 26282357 TI - Re: comparative effectiveness of shock wave lithotripsy and ureteroscopy for treating patients with kidney stones. PMID- 26282359 TI - Utility of event-related potentials in predicting antidepressant treatment response: An iSPOT-D report. AB - It is essential to improve antidepressant treatment of major depressive disorder (MDD) and one way this could be achieved is by reducing the number of treatment steps by employing biomarkers that can predict treatment outcome. This study investigated differences between MDD patients and healthy controls in the P3 and N1 component from the event-related potential (ERP) generated in a standard two tone oddball paradigm. Furthermore, the P3 and N1 are investigated as predictors for treatment outcome to three different antidepressants. In the international Study to Predict Optimized Treatment in Depression (iSPOT-D)--a multi-center, international, randomized, prospective practical trial--1008 MDD participants were randomized to escitalopram, sertraline or venlafaxine-XR. The study also recruited 336 healthy controls. Treatment response and remission were established after eight weeks using the 17-item Hamilton Rating Scale for Depression. P3 and N1 latencies and amplitudes were analyzed using a peak-picking approach and further replicated by using exact low resolution tomography (eLORETA). A reduced P3 was found in MDD patients compared to controls by a peak-picking analysis. This was validated in a temporal global field power analysis. Source density analysis revealed that the difference in cortical activity originated from the posterior cingulate and parahippocampal gyrus. Male non-responders to venlafaxine XR had significantly smaller N1 amplitudes than responders. This was demonstrated by both analytical methods. Male non-responders to venlafaxine-XR had less activity originating from the left insular cortex. The observed results are discussed from a neural network viewpoint. PMID- 26282360 TI - The neuroplastic index p-FADD/FADD and phosphoprotein PEA-15, interacting at GABAA receptor, are upregulated in brain cortex during midazolam-induced hypnosis in mice. AB - Fas-associated death domain (FADD) adaptor is involved in the signaling of metabotropic G protein-coupled receptors, whose agonists stimulate its phosphoryaltion (p) increasing p-FADD/FADD ratio in brain. Whether FADD might also participate in the activation of dissimilar receptors such as the ligand gated ion channels is not known. This study investigated the role of FADD and phosphoprotein-enriched in astrocytes of 15 kDa (PEA-15, a FADD partner) in the activation of gamma-aminobutyric acid-A (GABAA) receptor, which mediates the hypnotic effect of midazolam. The main findings revealed that during the time course of midazolam (60 mg/kg)-induced hypnosis in mice (about 2 h) p-FADD (and p FADD/FADD ratio) as well as p-PEA (and its phosphorylating Akt1 kinase) were markedly increased (36-80%) in brain cortex, and these effects were partially (only p-FADD) or fully prevented by flumazenil (a neutral allosteric ligand) and FG 7142 (a partial negative allosteric ligand) acting at GABAA receptors. The upregulation of cortical p-FADD/FADD was exclusively observed in the nucleus (up to 2.8-fold), where the transciption factor NF-kappaB was also increased (up to 46%), and that of p-PEA/p-Akt1 only in the cytosol (up to 53%), suggesting that p FADD/p-PEA/p-Akt1 are involved in sleep-induced neuroplasticity. Repeated treatment with midazolam (60 mg/kg, 4 days) induced behavioral (prolonged sleep latency and reduced sleeping time) and neurochemical (reduced p-FADD/p-PEA contents) tolerance. These findings indicated that p-FADD/p-PEA are novel molecules in GABAA receptor signaling and that cortical p-PEA and p-FADD, working in tandem, are involved in the complex molecular processes leading to the hypnotic effect of midazolam in mice. PMID- 26282361 TI - [Mycobacterial pulmonary infection due to Mycobacterium simiae]. AB - INTRODUCTION: Mycobacterium simiae pulmonary infections remain exceptional in France. CASE REPORT: We report a case of M. simiae lung infection and a 10-year follow-up in a non-immunocompromised host. CONCLUSION: This case emphasizes the difficulties of choosing the appropriate drugs and their side effects in the absence of any existing gold standard. PMID- 26282362 TI - Use of a Hunter Rod for Staged Reconstruction of Peroneal Tendons. AB - Peroneal tendon pathology is a commonly reported cause of lateral ankle pain. The causes include cavovarus foot type, overuse, chronic tendinosis, peroneal subluxation or dislocation, acute traumatic split tears, and traumatic rupture. The purpose of the present report is to describe an alternative approach for surgical reconstruction of the peroneal tendons in patients when repair might no longer be effective. The use of a Hunter rod was originally described by Hunter in 1971 for 2-stage reconstruction of tendons in the hand. We present a 2-stage surgical technique with the use of a Hunter rod as a temporary implant to stimulate generation of a healthy peroneal tendon sheath to host a flexor hallucis longus tendon transfer. This has proved to be a successful treatment option for patients with severe peroneal tendon damage and scarring along the peroneal tendon sheath. We offer a sample case to illustrate a patient with such indications. PMID- 26282363 TI - Time to pause, look back and plan for the future. PMID- 26282364 TI - Enhancing the contribution of research to health care policy-making: a case study of the Dutch Health Care Performance Report. AB - OBJECTIVES: The Dutch Health Care Performance Report, issued by the National Institute of Public Health and the Environment, aims to monitor health care performance in The Netherlands. Both the National Institute and the Ministry of Health wish to increase the contribution of the Report to health care policy making. Our aim was to identify ways to achieve that. METHOD: We used contribution mapping as a theoretical framework that recognizes alignment of research as crucial to managing contributions to policy-making. To investigate which areas need alignment efforts by researchers and/or policy-makers, we interviewed National Institute researchers and policy-makers from the Ministry of Health and assessed the process for developing the 2010 Report. RESULTS: We identified six areas where alignment is specifically relevant for enhancing the contributions of future versions of the Dutch Health Care Performance Report: well-balanced information for different ministerial directorates; backstage work; double role actors; reports of other knowledge institutes; data collection/generation and presentation forms. CONCLUSION: The contribution of health care performance reporting to policy-making is complex and requires continuous alignment efforts between researchers and policy-makers. These efforts should form an inseparable part of health care performance reporting and although this demands considerable resources, it is worth considering since it may pay back in better contributions to policy-making. PMID- 26282365 TI - Protection of the elite athlete is the responsibility of all of us in sports medicine. PMID- 26282366 TI - Because not all blows to the head are the same. PMID- 26282367 TI - Preventing penetrating hand injuries in sabre fencing: an application and critique of the van Mechelen model by the Federation Internationale d'Escrime. AB - BACKGROUND/AIM: To address the unusual phenomenon of unbroken blades causing penetrating hand injuries in sabre fencing by applying the van Mechelen model of the 'sequence of prevention'. METHODS: Cases were collected from three surveillance systems and snowball sampling, and examined for potential aetiological factors. Presumed contributing factors were evaluated against the available evidence to compile a viable list for change. Determining a prevention strategy was guided by the philosophy of developing an approach that was most likely to produce a meaningful reduction in these injuries with the least disruption to the current norms of competitive sabre fencing. RESULTS: Nine factors which contributed, either individually or in some combination, to these injuries were grouped under three headings relating to: (1) the nature of modern sabre fencing, (2) the design of the sabre blade and (3) the vulnerability of the hand. Changes to the design and integrity of sabre gloves were selected as the most feasible option and new standards were introduced as compulsory in international competitions from 1 April 2014. The effect of this change is now being monitored via available surveillance systems. CONCLUSIONS: The van Mechelen model is a useful framework for sports federations to apply to reduce injury risk, even for rare injuries. However, this research model has limitations in guiding the realities of sometimes competing interests among the scientific, political, financial and technical aspects of injury prevention interventions. PMID- 26282368 TI - Injury and illness surveillance during the 24th Men's Handball World Championship 2015 in Qatar. AB - BACKGROUND: The IOC encourages international federations to establish systematic athlete injury and illness surveillance programmes. OBJECTIVE: To describe pattern of injuries and illnesses during the 24th Men's Handball World Championship 2015 by implementing the IOC injury and illness surveillance protocol. METHODS: The medical staff of participating teams (n=24) were requested to report all new injuries and illnesses during matches and/or training on a daily basis throughout the event (15 January to 1 February, 2015). Exposure (number of player-hours) during all matches was calculated for all players (n=384) and for each of the 4 player positions (wing, back, line and goalkeeper). RESULTS: Medical staff of all teams submitted 96.7% (n=325) of the daily report forms. In total, 27.1% of the players were injured, and of the 132 injuries reported, 40% were time-loss injuries. The total incidence of injuries was 104.5 per 1000 player-hours. The highest risk of injury was found among line players, and more injuries occurred during the first half of the matches. The most frequent injury location was the ankle, followed by the thigh, knee and head/face. The majority of injuries were contusion, sprain or strain. In total, 10.9% of the players were affected by an illness during the event. Of the 42 cases recorded, 31 (73.8%) were reported as respiratory tract infection. CONCLUSIONS: The risk of injury in handball is high among Olympic sports. Preventive measures should focus on contusions, ankle sprains, and thigh muscle strains, as well as measures aimed to reduce upper respiratory tract infections. PMID- 26282369 TI - Acute infection with bovine viral diarrhea virus of low or high virulence leads to depletion and redistribution of WC1(+) gammadelta T cells in lymphoid tissues of beef calves. AB - The objective of this study was to determine the abundance and distribution of gammadelta T lymphocytes in lymphoid tissue during acute infection with high (HV) or low virulence (LV) non-cytopathic bovine viral diarrhea virus (BVDV) in beef calves. This study was performed using tissue samples from a previous experiment in which thirty beef calves were randomly assigned to 1 of 3 groups: LV [n=10; animals inoculated intranasally (IN) with LV BVDV-1a (strain SD-1)], HV [n=10; animals inoculated IN with HV BVDV-2 (strain 1373)], and control (n=10; animals inoculated with cell culture medium). On day 5 post inoculation, animals were euthanized, and samples from spleen and mesenteric lymph nodes (MLN) were collected to assess the abundance of WC1(+) gammadelta T cells. A higher proportion of calves challenged with BVDV showed signs of apoptosis and cytophagy in MLN and spleen samples compared to the control group. A significantly lower number of gammadelta T cells was observed in spleen and MLN from calves in HV and LV groups than in the control calves (P<0.05). In conclusion, acute infection with HV or LV BVDV resulted in depletion of WC1(+) gammadelta T cells in mucosal and systemic lymphoid tissues at five days after challenge in beef calves. This reduction in gammadelta T cells in the studied lymphoid tissues could be also due to lymphocyte trafficking to other tissues. PMID- 26282370 TI - Amygdaloid zif268 participated in the D-cycloserine facilitation effect on the extinction of conditioned fear. AB - RATIONALE: The involvement of glutamate in fear extinction is perhaps the most promising in terms of facilitating clinical interventions for posttraumatic stress disorder (PTSD). This study was aimed at elucidating the possible role of zif268 on the D-cycloserine (DCS) facilitation effect on extinction. OBJECTIVE: We investigated the association between zif268 and the extinction of conditioned fear by using antisense oligodeoxynucleotide (ODN) of zif268 and the fear potentiated startle paradigm. METHODS: Male adult Wistar rats were injected DCS (15 mg/kg, IP) 15 min prior to the extinction training, administered with antisense or sense ODN (800 pmol) of zif268 and subjected for fear-potentiated startle paradigm (FPS) and Western blot. RESULTS: Either context exposure or cue exposure elevated the expression of zif268 in the basolateral nucleus of the amygdala (BLA) (p < 0.05 and p < 0.01, respectively) compared to the control group. Additionally, zif268 expression in BLA was further elevated by the glutamate NMDA receptor agonist DCS administration. Intra-amygdaloid injection of the antisense ODN of zif268 blocked the facilitation effect of DCS on the extinction of conditioned fear. Subsequent control experiments indicated that administration of vehicle or zif268 sense ODN did not alter the facilitation of DCS and that the blockage effect of zif268 antisense ODN was not due to lasting damage to the amygdala. CONCLUSIONS: Our results suggest that zif268 within the amygdala participates in the DCS facilitation effect on the extinction of conditioned fear. PMID- 26282371 TI - Assessment of total silver and silver nanoparticle extraction from medical devices. AB - There is concern over the release of silver nanoparticles (AgNPs) from medical devices due to their potential toxicological consequences inside the body. Towards developing the exposure component of a risk assessment model, the purpose of this study was to determine the amount and physical form of silver released from medical devices. Scanning electron microscopy was used to confirm that three of five marketed medical devices contained nanosilver coatings (mean feature sizes 115-341 nm). Aqueous device extracts (water, saline and human plasma) were analyzed with inductively coupled plasma mass spectrometry, ultraviolet-visible spectroscopy, dynamic light scattering, transmission electron microscopy, and nanoparticle tracking analysis. The amount of silver extracted from the devices ranged from 1 * 10(-1) to 1 * 10(6) ng/cm(2) (conditions ranged from 37 to 50 degrees C, over one hour to seven days). The results further indicated that one of the five devices (labeled MD1) released significantly more AgNPs than the other devices. This data suggests that some but not all devices that are formulated with nanosilver may release detectable levels of AgNPs upon extraction. Further work is underway to quantitate the proportion of silver released as AgNPs and to incorporate this data into a risk assessment for AgNP exposure from medical devices. PMID- 26282372 TI - Potential toxic effects of glyphosate and its commercial formulations below regulatory limits. AB - Glyphosate-based herbicides (GlyBH), including Roundup, are the most widely used pesticides worldwide. Their uses have increased exponentially since their introduction on the market. Residue levels in food or water, as well as human exposures, are escalating. We have reviewed the toxic effects of GlyBH measured below regulatory limits by evaluating the published literature and regulatory reports. We reveal a coherent body of evidence indicating that GlyBH could be toxic below the regulatory lowest observed adverse effect level for chronic toxic effects. It includes teratogenic, tumorigenic and hepatorenal effects. They could be explained by endocrine disruption and oxidative stress, causing metabolic alterations, depending on dose and exposure time. Some effects were detected in the range of the recommended acceptable daily intake. Toxic effects of commercial formulations can also be explained by GlyBH adjuvants, which have their own toxicity, but also enhance glyphosate toxicity. These challenge the assumption of safety of GlyBH at the levels at which they contaminate food and the environment, albeit these levels may fall below regulatory thresholds. Neurodevelopmental, reproductive, and transgenerational effects of GlyBH must be revisited, since a growing body of knowledge suggests the predominance of endocrine disrupting mechanisms caused by environmentally relevant levels of exposure. PMID- 26282374 TI - Stability and synchronization of memristor-based fractional-order delayed neural networks. AB - Global asymptotic stability and synchronization of a class of fractional-order memristor-based delayed neural networks are investigated. For such problems in integer-order systems, Lyapunov-Krasovskii functional is usually constructed, whereas similar method has not been well developed for fractional-order nonlinear delayed systems. By employing a comparison theorem for a class of fractional order linear systems with time delay, sufficient condition for global asymptotic stability of fractional memristor-based delayed neural networks is derived. Then, based on linear error feedback control, the synchronization criterion for such neural networks is also presented. Numerical simulations are given to demonstrate the effectiveness of the theoretical results. PMID- 26282373 TI - Delirium superimposed on dementia: A quantitative and qualitative evaluation of patient experience. AB - OBJECTIVE: Delirium superimposed on dementia is common and is associated with adverse outcomes. Yet little is known about the patients' personal delirium experiences. We used quantitative and qualitative methods to assess the delirium superimposed on dementia experience among older patients. METHODS: We conducted a prospective cohort study among patients with delirium superimposed on dementia who were admitted to a rehabilitation ward. Delirium was diagnosed using DSM-IV TR criteria. Delirium severity and symptoms were evaluated with the Delirium-O Meter (D-O-M). The experience of delirium was assessed after delirium resolution (T0) and one month later (T1) with a standardized questionnaire and a qualitative interview. Level of distress was measured with the Delirium Experience Questionnaire. RESULTS: Of the 30 patients included in the study, 50% had mild dementia; 33% and 17% had moderate and severe dementia. Half of the patients had evidence of the full range of D-O-M delirium symptoms. We evaluated 30 patients at T0 and 20 at T1. At T0, half of the patients remembered being confused as part of the delirium episode, and reported an overall moderate level of related distress. Patients reported high distress related to memories of anxiety/fear, delusions, restlessness, hypokinesia, and impaired orientation. Qualitative interviews revealed six main aspects of patient delirium experiences: Emotions; Cognitive Impairment; Psychosis; Memories; Awareness of Change; and Physical Symptoms. CONCLUSIONS: The study provides novel information on the delirium experience in patients with dementia. These findings are the key for health care providers to improve the everyday care of this important group of frail older patients. PMID- 26282375 TI - The effect of force-controlled biting on human posture control. AB - Several studies have confirmed the neuromuscular effects of jaw motor activity on the postural stability of humans, but the mechanisms of functional coupling of the craniomandibular system (CMS) with human posture are not yet fully understood. The purpose of our study was, therefore, to investigate whether submaximum biting affects the kinematics of the ankle, knee, and hip joints and the electromyographic (EMG) activity of the leg muscles during bipedal narrow stance and single-leg stance. Twelve healthy young subjects performed force controlled biting (FB) and non-biting (NB) during bipedal narrow stance and single-leg stance. To investigate the effects of FB on the angles of the hip, knee, and ankle joints, a 3D motion-capture system (Vicon MX) was used. EMG activity was recorded to enable analysis of the coefficient of variation of the muscle co-contraction ratios (CVR) of six pairs of postural muscles. Between FB and NB, no significant differences were found for the mean values of the angles of the ankle, knee, and hip joints, but the standard deviations were significantly reduced during FB. The values of the ranges of motion and the mean angular velocities for the three joints studied revealed significant reduction during FB also. CVR was also significantly reduced during FB for five of the six muscle pairs studied. Although submaximum biting does not change the basic strategy of posture control, it affects neuromuscular co-contraction patterns, resulting in increased kinematic precision. PMID- 26282376 TI - Experimental colitis in SIV-uninfected rhesus macaques recapitulates important features of pathogenic SIV infection. AB - Mucosal damage to the gastrointestinal (GI) tract with resulting microbial translocation is hypothesized to significantly contribute to the heightened and persistent chronic inflammation and immune activation characteristic to HIV infection. Here we employ a non-human primate model of chemically induced colitis in SIV-uninfected rhesus macaques that we developed using dextran sulfate sodium (DSS), to directly test this hypothesis. DSS treatment results in GI barrier damage with associated microbial translocation, inflammation and immune activation. The progression and severity of colitis are longitudinally monitored by a magnetic resonance imaging approach. DSS treatment of SIV-infected African green monkeys, a natural host species for SIV that does not manifest GI tract damage or chronic immune activation during infection, results in colitis with elevated levels of plasma SIV RNA, sCD14, LPS, CRP and mucosal CD4+ T-cell loss. Together these results support the hypothesis that GI tract damage leading to local and systemic microbial translocation, and associated immune activation, are important determinants of AIDS pathogenesis. PMID- 26282378 TI - Induction of oxidative stress by Taxol(r) vehicle Cremophor-EL triggers production of interleukin-8 by peripheral blood mononuclear cells through the mechanism not requiring de novo synthesis of mRNA. AB - Understanding the ability of cytotoxic oncology drugs, and their carriers and formulation excipients, to induce pro-inflammatory responses is important for establishing safe and efficacious formulations. Literature data about cytokine response induction by the traditional formulation of paclitaxel, Taxol(r), are controversial, and no data are available about the pro-inflammatory profile of the nano-albumin formulation of this drug, Abraxane(r). Herein, we demonstrate and explain the difference in the cytokine induction profile between Taxol(r) and Abraxane(r), and describe a novel mechanism of cytokine induction by a nanosized excipient, Cremophor EL, which is not unique to Taxol(r) and is commonly used in the pharmaceutical industry for delivery of a wide variety of small molecular drugs. FROM THE CLINICAL EDITOR: Advances in nanotechnology have enabled the production of many nano-formulation drugs. The cellular response to drugs has been reported to be different between traditional and nano-formulations. In this article, the authors investigated and compared cytokine response induction profiles between Taxol(r) and Abraxane(r). The findings here provided further understanding to create drugs with better safety profiles. PMID- 26282379 TI - Assessment of beta-lapachone loaded in lecithin-chitosan nanoparticles for the topical treatment of cutaneous leishmaniasis in L. major infected BALB/c mice. AB - Patients affected by cutaneous leishmaniasis need a topical treatment which cures lesions without leaving scars. Lesions are produced not only by the parasite but also by an uncontrolled and persistent inflammatory immune response. In this study, we proposed the loading of beta-lapachone (beta-LP) in lecithin-chitosan nanoparticles (NP) for targeting the drug to the dermis, where infected macrophages reside, and promote wound healing. Although the loading of beta-LP in NP did not influence the drug antileishmanial activity it was critical to achieve important drug accumulation in the dermis and permeation through the skin. When topically applied in Leishmania major infected BALB/c mice, beta-LP NP achieved no parasite reduction but they stopped the lesion progression. Immuno histopathological assays in CL lesions and quantitative mRNA studies in draining lymph nodes confirmed that beta-LP exhibited anti-inflammatory activity leading to the down-regulation of IL-1beta and COX-2 expression and a decrease of neutrophils infiltrate. FROM THE CLINICAL EDITOR: Cutaneous leishmaniasis often leaves patients with unsightly scars due to the body's inflammatory response to the infection. The authors in this paper described topical treatment using beta lapachone (beta- LP) loaded in lecithin-chitosan nanoparticles (NP) in an animal model. Results confirmed the reduction of inflammatory response without affecting the parasite killing efficacy. These findings would pave way for further clinical testing in the near future. PMID- 26282377 TI - Design considerations for nanotherapeutics in oncology. AB - Nanotherapeutics have improved the quality of life of cancer patients, primarily by reducing the adverse effects of chemotherapeutic agents, but improvements in overall survival are modest. This is in large part due to the fact that the enhanced permeability and retention effect, which is the basis for the use of nanoparticles in cancer, can be also a barrier to the delivery of nanomedicines. A careful design of nanoparticle formulations can overcome barriers posed by the tumor microenvironment and result in better treatments. In this review, we first discuss strengths and limitations of clinically-approved nanoparticles. Then, we evaluate design parameters that can be modulated to optimize delivery. The benefits of active tumor targeting and drug release rate on intratumoral delivery and treatment efficacy are also discussed. Finally, we suggest specific design strategies that should optimize delivery to most solid tumors and discuss under what conditions active targeting would be beneficial. FROM THE CLINICAL EDITOR: Advances in nanotechnology have seen the introduction of new treatment modalities for cancer. The principle of action using nanocarriers for drug delivery is based mostly on the Enhanced Permeability and Retention effect. This phenomenon however, can also be a hindrance. In this article, the authors performed an in depth review on various nanoparticle platforms in cancer therapeutics. They also suggested options to improve drug delivery, in terms of carrier design. PMID- 26282380 TI - In vitro anti-cancer effects of artemisone nano-vesicular formulations on melanoma cells. AB - Artemisone is a 10-amino-artemisinin derivative that is markedly superior in vitro and in vivo to current artemisinins against malaria and also possesses antitumor activity. In seeking to capitalise on the last property, we have examined the encapsulation of artemisone in nano-vesicular niosomes and solid lipid nanoparticles, and have evaluated efficacies of the free and encapsulated artemisone against human melanoma A-375 cells and effects on human keratinocytes (HaCaT). Artemisone is successfully encapsulated into the nano-vesicles with encapsulation efficiencies of 67+/-6% and 79+/-5%, and with average particle sizes being 211+/-10nm and 295+/-18nm respectively. The formulations displayed highly selective cytotoxicity towards the melanoma cells with negligible toxicity towards the normal skin cells. The artemisone-loaded nano-vesicles almost completely inhibited the melanoma cells compared to the free drug. The results overall suggest a potentially more useful therapeutic strategy that needs to be evaluated for the treatment of melanoma and other cancers. FROM THE CLINICAL EDITOR: Apart from being an effective anti-malarial drug, a surprising action of artemisone also has antitumor activity. Nonetheless, its low water solubility and bioavailability has limited its clinical use. In this article, the authors enacapsulated artemisone in nano- vesicles and solid lipid nano-particles (SLNs). In-vitro studies confirmed the selective cytotoxicity towards melanoma cells. Further in-vivo and pre-clinical studies are awaited. PMID- 26282382 TI - Whole-animal mounts of Caenorhabditis elegans for 3D imaging using atomic force microscopy. AB - The 3D surface of Caenorhabditis elegans was imaged at nanometer resolution using atomic force microscopy (AFM). Oscillation of a medium stiffness silicon AFM cantilever at the upper second amplitude peak, typically 6 times above the fundamental frequency, vastly improved image quality on the moist, sticky, and soft worms. Whole-animal mounts of normal and double-headed mutants of the nematode worm were prepared and scanned. Well-preserved anatomical features including annuli, furrows, alae, and rows of never before seen nanometer-sized pores dotting the molted worm's outermost surface coat were resolved. Well preserved anatomical features including annuli, furrows, alae, and rows of nanometer-sized pores or struts dotting the molted worm's outermost surface were resolved. This AFM method represents a simple and rapid new approach for nanometer-resolved 3D imaging and analysis of whole-animal specimens of C. elegans. FROM THE CLINICAL EDITOR: In this interesting article the authors describe a new AFM sampling method to allow better images on whole-animal mounts such as C. elegans. This method would generate more information and in the future may be useful for differentiating even individual animals with different genetic backgrounds. PMID- 26282383 TI - Silver nanoparticles promote osteogenesis of mesenchymal stem cells and improve bone fracture healing in osteogenesis mechanism mouse model. AB - The potential use of osteo-conducive biomaterials in the promotion of bone fracture healing has attracted wide attention. This study investigated if silver nanoparticles (AgNps) could promote the proliferation and osteogenesis of mesenchymal stem cells (MSCs), and improve bone fracture healing. We showed that AgNps promoted MSCs' proliferation and osteogenic differentiation in vitro. Using a mouse femoral facture model, AgNps encapsulated in collagen promoted the formation of fracture callus, and induced early closure of the fracture gap. AgNps may promote the formation of the callus and the subsequent end joining of the fracture bone via multiple routes: (i) chemo-attraction of MSCs and fibroblasts to migrate to the fracture site; (ii) induction of the proliferation of MSCs; (iii) induction of osteogenic differentiation of MSCs via induction/activation of TGF-beta/BMP signaling in MSCs. We concluded that AgNps might be beneficial as an adjunct treatment for bone fracture healing clinically. FROM THE CLINICAL EDITOR: Silver nanoparticles are widely used in wound management in the clinical setting. In this article, the authors demonstrated a novel application in that these nanoparticles were efficient in promoting osteoblastic differentiation in both in-vitro and in-vivo studies. The findings may provide a new treatment direction for bone fracture in the future. PMID- 26282384 TI - The influence of intraocular pressure and air jet pressure on corneal contactless tonometry tests. AB - The air puff is a dynamic contactless tonometer test used in ophthalmology clinical practice to assess the biomechanical properties of the human cornea and the intraocular pressure due to the filling fluids of the eye. The test is controversial, since the dynamic response of the cornea is governed by the interaction of several factors which cannot be discerned within a single measurement. In this study we describe a numerical model of the air puff tests, and perform a parametric analysis on the major action parameters (jet pressure and intraocular pressure) to assess their relevance on the mechanical response of a patient-specific cornea. The particular cornea considered here has been treated with laser reprofiling to correct myopia, and the parametric study has been conducted on both the preoperative and postoperative geometries. The material properties of the cornea have been obtained by means of an identification procedure that compares the static biomechanical response of preoperative and postoperative corneas under the physiological IOP. The parametric study on the intraocular pressure suggests that the displacement of the cornea's apex can be a reliable indicator for tonometry, and the one on the air jet pressure predicts the outcomes of two or more distinct measurements on the same cornea, which can be used in inverse procedures to estimate the material properties of the tissue. PMID- 26282381 TI - 3D tumor tissue analogs and their orthotopic implants for understanding tumor targeting of microenvironment-responsive nanosized chemotherapy and radiation. AB - An appropriate representation of the tumor microenvironment in tumor models can have a pronounced impact on directing combinatorial treatment strategies and cancer nanotherapeutics. The present study develops a novel 3D co-culture spheroid model (3D TNBC) incorporating tumor cells, endothelial cells and fibroblasts as color-coded murine tumor tissue analogs (TTA) to better represent the tumor milieu of triple negative breast cancer in vitro. Implantation of TTA orthotopically in nude mice, resulted in enhanced growth and aggressive metastasis to ectopic sites. Subsequently, the utility of the model is demonstrated for preferential targeting of irradiated tumor endothelial cells via radiation-induced stromal enrichment of galectin-1 using anginex conjugated nanoparticles (nanobins) carrying arsenic trioxide and cisplatin. Demonstration of a multimodal nanotherapeutic system and inclusion of the biological response to radiation using an in vitro/in vivo tumor model incorporating characteristics of tumor microenvironment presents an advance in preclinical evaluation of existing and novel cancer nanotherapies. FROM THE CLINICAL EDITOR: Existing in vivo tumor models are established by implanting tumor cells into nude mice. Here, the authors described their approach 3D spheres containing tumor cells, enodothelial cells and fibroblasts. This would mimic tumor micro-environment more realistically. This interesting 3D model should reflect more accurately tumor response to various drugs and would enable the design of new treatment modalities. PMID- 26282385 TI - A simple, effective and clinically applicable method to compute abdominal aortic aneurysm wall stress. AB - Abdominal aortic aneurysm (AAA) is a permanent and irreversible dilation of the lower region of the aorta. It is a symptomless condition that if left untreated can expand to the point of rupture. Mechanically-speaking, rupture of an artery occurs when the local wall stress exceeds the local wall strength. It is therefore desirable to be able to non-invasively estimate the AAA wall stress for a given patient, quickly and reliably. In this paper we present an entirely new approach to computing the wall tension (i.e. the stress resultant equal to the integral of the stresses tangent to the wall over the wall thickness) within an AAA that relies on trivial linear elastic finite element computations, which can be performed instantaneously in the clinical environment on the simplest computing hardware. As an input to our calculations we only use information readily available in the clinic: the shape of the aneurysm in-vivo, as seen on a computed tomography (CT) scan, and blood pressure. We demonstrate that tension fields computed with the proposed approach agree well with those obtained using very sophisticated, state-of-the-art non-linear inverse procedures. Using magnetic resonance (MR) images of the same patient, we can approximately measure the local wall thickness and calculate the local wall stress. What is truly exciting about this simple approach is that one does not need any information on material parameters; this supports the development and use of patient-specific modelling (PSM), where uncertainty in material data is recognised as a key limitation. The methods demonstrated in this paper are applicable to other areas of biomechanics where the loads and loaded geometry of the system are known. PMID- 26282386 TI - Estimating usual intakes mainly affects the micronutrient distribution among infants, toddlers and pre-schoolers from the 2012 Mexican National Health and Nutrition Survey. AB - OBJECTIVE: To compare estimates from one day with usual intake estimates to evaluate how the adjustment for within-person variability affected nutrient intake and adequacy in Mexican children. DESIGN: In order to obtain usual nutrient intakes, the National Cancer Institute's method was used to correct the first 24 h dietary recall collected in the entire sample (n 2045) with a second 24 h recall collected in a sub-sample (n 178). We computed estimates of one-day and usual intakes of total energy, fat, Fe, Zn and Na. SETTING: 2012 Mexican National Health and Nutrition Survey. SUBJECTS: A total of 2045 children were included: 0-5.9 months old (n 182), 6-11.9 months old (n 228), 12-23.9 months old (n 537) and 24-47.9 months old (n 1098). From these, 178 provided an additional dietary recall. RESULTS: Although we found small or no differences in energy intake (kJ/d and kcal/d) between one-day v. usual intake means, the prevalence of inadequate and excessive energy intake decreased somewhat when using measures of usual intake relative to one day. Mean fat intake (g/d) was not different between one-day and usual intake among children >6 months old, but the prevalence of inadequate and excessive fat intake was overestimated among toddlers and pre schoolers when using one-day intake (P6 months. CONCLUSIONS: There was overall low variability in energy and fat intakes but higher for micronutrients. Because the usual intake distributions are narrower, the prevalence of inadequate/excessive intakes may be biased when estimating nutrient adequacy if one day of data is used. PMID- 26282387 TI - Psychosocial Factors Predict Pain and Physical Health After Lower Extremity Trauma. AB - BACKGROUND: There has been increasing evidence to support the importance of psychosocial factors to poor outcomes after trauma. However, little is known about the contribution of pain catastrophizing and fear of movement to persistent pain and disability. QUESTIONS/PURPOSES: Therefore, we aimed to determine whether (1) high pain catastrophizing scores are independently associated with pain intensity or pain interference; (2) high fear of movement scores are independently associated with decreased physical health; and (3) depressive symptoms are independently associated with pain intensity, pain interference, or physical health at 1 year after accounting for patient characteristics of age and education. METHODS: Of 207 eligible patients, we prospectively enrolled 134 patients admitted to a Level I trauma center for surgical treatment of a fracture to the lower extremity. Sixty percent of patients (80 of 134) had an isolated lower extremity injury and the remainder sustained additional minor injury to the head/spine, abdomen/thorax, or upper extremity. Pain catastrophizing was measured with the Pain Catastrophizing Scale, fear of movement with the Tampa Scale for Kinesiophobia, and depressive symptoms with the Patient Health Questionnaire. Pain and physical health outcomes were assessed with the Brief Pain Inventory and the SF-12, respectively. Assessments were completed at 4 weeks and 1 year after hospitalization. Multiple variable hierarchical linear regression analyses were used to address study hypotheses. One hundred ten patients (82%) completed the 1 year followup. RESULTS: Pain catastrophizing at 4 weeks was associated with pain intensity (beta = 0.67; p < 0.001) and pain interference (beta = 0.38; p = 0.03) at 1 year. No association was found between fear of movement and physical health (beta = 0.15; p = 0.34). Depressive symptoms at 4 weeks were associated with pain intensity (beta = 0.49; p < 0.001), pain interference (beta = 0.51; p < 0.001), and physical health (beta = -0.32; p = 0.01) at 1 year. CONCLUSIONS: Catastrophizing behavior patterns and depressive symptoms are associated with more severe pain and worse function after traumatic lower extremity injury. Cognitive and behavioral strategies that have proven effective for chronic pain populations may be beneficial for trauma patients. Future research is needed to determine whether the early identification and treatment of subgroups of at-risk patients based on catastrophizing behavior or depressive symptoms can improve long-term outcomes. LEVEL OF EVIDENCE: Level I, prognostic study. PMID- 26282388 TI - Global Rating Scales and Motion Analysis Are Valid Proficiency Metrics in Virtual and Benchtop Knee Arthroscopy Simulators. AB - BACKGROUND: Work-hour restrictions and fatigue management strategies in surgical training programs continue to evolve in an effort to improve the learning environment and promote safer patient care. In response, training programs must reevaluate how various teaching modalities such as simulation can augment the development of surgical competence in trainees. For surgical simulators to be most useful, it is important to determine whether surgical proficiency can be reliably differentiated using them. To our knowledge, performance on both virtual and benchtop arthroscopy simulators has not been concurrently assessed in the same subjects. QUESTIONS/PURPOSES: (1) Do global rating scales and procedure time differentiate arthroscopic expertise in virtual and benchtop knee models? (2) Can commercially available built-in motion analysis metrics differentiate arthroscopic expertise? (3) How well are performance measures on virtual and benchtop simulators correlated? (4) Are these metrics sensitive enough to differentiate by year of training? METHODS: A cross-sectional study of 19 subjects (four medical students, 12 residents, and three staff) were recruited and divided into 11 novice arthroscopists (student to Postgraduate Year [PGY] 3) and eight proficient arthroscopists (PGY 4 to staff) who completed a diagnostic arthroscopy and loose-body retrieval in both virtual and benchtop knee models. Global rating scales (GRS), procedure times, and motion analysis metrics were used to evaluate performance. RESULTS: The proficient group scored higher on virtual (14 +/- 6 [95% confidence interval {CI}, 10-18] versus 36 +/- 5 [95% CI, 32-40], p < 0.001) and benchtop (16 +/- 8 [95% CI, 11-21] versus 36 +/- 5 [95% CI, 31-40], p < 0.001) GRS scales. The proficient subjects completed nearly all tasks faster than novice subjects, including the virtual scope (579 +/-169 [95% CI, 466-692] versus 358 +/- 178 [95% CI, 210-507] seconds, p = 0.02) and benchtop knee scope + probe (480 +/- 160 [95% CI, 373-588] versus 277 +/- 64 [95% CI, 224 330] seconds, p = 0.002). The built-in motion analysis metrics also distinguished novices from proficient arthroscopists using the self-generated virtual loose body retrieval task scores (4 +/- 1 [95% CI, 3-5] versus 6 +/- 1 [95% CI, 5-7], p = 0.001). GRS scores between virtual and benchtop models were very strongly correlated (rho = 0.93, p < 0.001). There was strong correlation between year of training and virtual GRS (rho = 0.8, p < 0.001) and benchtop GRS (rho = 0.87, p < 0.001) scores. CONCLUSIONS: To our knowledge, this is the first study to evaluate performance on both virtual and benchtop knee simulators. We have shown that subjective GRS scores and objective motion analysis metrics and procedure time are valid measures to distinguish arthroscopic skill on both virtual and benchtop modalities. Performance on both modalities is well correlated. We believe that training on artificial models allows acquisition of skills in a safe environment. Future work should compare different modalities in the efficiency of skill acquisition, retention, and transferability to the operating room. PMID- 26282389 TI - Musculoskeletal Medicine Is Underrepresented in the American Medical School Clinical Curriculum. AB - BACKGROUND: Musculoskeletal (MSK) conditions are common, and their burden on the healthcare system is increasing as the general population ages. It is essential that medical students be well prepared to evaluate and treat MSK disorders in a confident manner as they enter the workforce. Recent studies and the American Association of Medical Colleges have raised concern that medical schools may not give sufficient instruction on this topic. Other authors have shown that preclinical instruction has increased over the past decade; however, it is unclear if required clinical instruction also has followed that trend. QUESTIONS/PURPOSES: The purposes of this study were: (1) to assess the presence and duration of required or selective instruction in a MSK medicine specialty within the clinical years of undergraduate medical education; and (2) to assess the current state of requirements of clinical clerkships or rotations in other surgical and nonsurgical fields for comparison with the initial findings. METHODS: The web sites of all 141 US medical schools were assessed to determine the content of their clinical curricula for the 2014-2015 academic year; five were excluded because they had not yet had a graduating class by the conclusion of the 2014-2015 academic year. Complete information on required rotations was obtained through the schools' web sites for all 136 (100%) medical schools. For selective experience during the surgery clerkships, complete information was available for 130 of the remaining 136 (96%) web sites. RESULTS: Mean (in weeks, +/- SD) duration of core clerkships were as follows: internal medicine (10 +/- 2), surgery (8 +/- 2), pediatrics (7 +/- 1), obstetrics/gynecology (6 +/- 1), and psychiatry (5 +/- 1). Other common required clerkships were: family medicine (required in 96% [131 of 136] of schools, mean duration of 6 +/- 2 weeks), neurology (81% [110], 4 +/- 1), and emergency medicine (55% [75], 3 +/- 1). Required MSK instruction, at a mean of 2 +/- 1 weeks, was only present in 15% (20 of 136) of medical schools. In addition, clinical MSK instruction was offered as a selective (eg, students pick from a selection of subspecialties such as orthopaedics, plastics, or urology during a general surgery clerkship) in 34% (44 of 130) of all medical schools. This is less than other non-core specialties: geriatrics/ambulatory care (required in 40% [54 of 136] of schools, mean duration of 3 +/- 1 weeks), critical care (30% [41], mean of 3 +/- 1 weeks), radiology (26% [35], mean of 3 +/- 1 weeks), anesthesiology (23% [31], mean of 2 +/- 1 weeks), and other surgical subspecialties (19% [26], mean of 3 +/- 1weeks). CONCLUSIONS: Traditional core clerkships continue to be well represented in the clinical years, whereas three newer specialties have gained a larger presence: family medicine, neurology, and emergency medicine; these comprise the "big eight" of clinical clerkships. Given the high prevalence and burden of MSK disorders, required experience in MSK medicine continues to be underrepresented. Further discussion at a national level is needed to determine appropriate representation of MSK medicine specialties during the clinical years. PMID- 26282390 TI - Major Ozonated Autohemotherapy Preconditioning Ameliorates Kidney Ischemia Reperfusion Injury. AB - Medical ozone has therapeutic properties as an antimicrobial, anti-inflammatory, modulator of antioxidant defense system. Major ozonated autohemotherapy (MOA) is a new therapeutic approach that is widely used in the treatment of many diseases. The objective of the present study was to determine whether preischemic application of MOA would attenuate renal ischemia-reperfusion injury (IRI) in rabbits. Twenty-four male New Zealand white rabbits were divided into four groups, each including six animals: (1) Sham-operated group, (2) Ozone group (the MOA group without IRI), (3) IR group (60 min ischemia followed by 24 h reperfusion), and (4) IR + MOA group (MOA group). The effects of MOA were examined by use of hematologic and biochemical parameters consisting of neutrophil to lymphocyte ratio (NLR), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), ischemia-modified albumin (IMA), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI). In addition, the histopathological changes including the tubular brush border loss (TBBL), tubular cast (TC), tubular necrosis (TN), intertubular hemorrhage and congestion (IHC), dilatation of bowman space (DBS), and interstitial inflammatory cells infiltration (IECI) were evaluated. In the IR group, compared to the Sham group, biochemical parameters indicating oxidative stress, NLR, IL-6, TNF-alpha, IMA, TOS, and OSI have increased. MOA reduced inflammation and oxidative stress parameters. Although TAS values have decreased in the IR group and increased in the MOA-pretreated group, no significant changes in TAS values were detected between the IR and MOA groups. The total score was obtained by summing all the scores from morphological kidney damage markers. The total score has increased with IR damage when compared with the Sham group (13.83 +/- 4.30 vs 1.51 +/- 1.71; p = 0.002). But, the total score has decreased significantly after application of MOA (5.01 +/- 1.49; p = 0.002; compared with the IR group). MOA preconditioning is effective in reducing tissue damage induced in kidney ischemia reperfusion injury. The protective effect of MOA is mediated via reducing inflammatory response and regulating of reactive oxygen species (ROS). Renal histology also showed convincing evidence regarding MOA's protective nature against kidney injury induced renal ischemia-reperfusion. Consequently, MOA might be helpful in protecting the kidneys from IR-induced damage in humans, probably through the anti-inflammatory effect and reducing the total oxidant status. PMID- 26282391 TI - Piperazine linked salicylaldoxime and salicylaldimine-based dicopper(ii) receptors for anions. AB - The syntheses and single crystal X-ray analyses of five strapped salicylaldoxime/salicylaldimine based dicopper(ii) receptors utilising a new piperazine linker are described. The complexes form 2 + 2 metallocycles and the molecular structures of all four complexes possess a small internal cavity with the utilisation of a short piperazine linker. The molecular structures of complexes [Cu2(L(4) - H)(L(4) - 2H) ? DMF]BF4.DMF, and [Cu2(L(4) - H)2Br]Br.1.25DMSO.H2O.MeOH, show that intramolecular H-bonding interactions due to the presence of -OH (oxime moiety) groups lead to a Pacman-like cleft arrangement of the two metal coordinating subunits in the metallo-macrocycle. The geometrical constraints brought about by this constrained cleft make the receptor coordinate strongly to a bromide anion involving both metal centres as evidenced by whereas in the larger tetrafluroborate anion is excluded. Absence of the oxime moiety around the metal coordination site of the ligand as demonstrated in the complexes [Cu2(L(5))2BF4](BF4)3, and [Cu2(L(5))2Br]Br3.2MeOH, resulted in less constrained dicopper(ii) helicate forms. For these complexes no anion size discrimination was observed. The addition of pyridine solvent to a slightly modified piperazine-linked ligand produces an expanded 3 + 3 tube-like tricopper complex [Cu3(L(4a) - H)3Py3](BF4)2.(MeOH)3.PF6.(H2O)3, , with two coordinated pyridine molecules occupying the newly formed cavity. PMID- 26282392 TI - Global travel patterns and risk of measles in Ontario and Quebec, Canada: 2007 2011. AB - BACKGROUND: In 2011 the largest measles outbreak in North America in a decade occurred in Quebec, Canada with over 700 cases. In contrast, measles activity in neighbouring province Ontario remained low (8 cases). Our objective was to determine the extent to which the difference could be explained by differing travel patterns. METHODS: We explored the relationship between measles cases over 2007-2011, by importation classification, in Quebec and Ontario in relation to global travel patterns to each province using an ecological approach. Global measles exposure was estimated by multiplying the monthly traveler volume for each country of origin into Quebec or Ontario by the yearly measles incidence rate for the corresponding country. Visual inspection of temporal figures and calculation of Pearson correlation coefficients were performed. RESULTS: Global measles exposure was similar in Ontario and Quebec. In Quebec, there was a nearly perfectly linear relationship between annual measles cases and its global measles exposure index over 2007-2011 (r = 0.99, p = 0.001). In contrast, there was a non significant association in Ontario. The 2011 rise in Quebec's index was largely driven by a dramatic increase in measles activity in France the same year. CONCLUSIONS: Global measles activity was associated with measles epidemiology in Quebec. Global measles exposure risk is higher in Ontario than Quebec. Differences in measles epidemiology between Ontario and Quebec from 2007-2011 are not explained by greater exposure in Quebec. A combination of alternative factors may be responsible, including differences in population susceptibility. PMID- 26282393 TI - Predictive factors for post-operative drainage after partial superficial parotidectomy: a case-control study. AB - OBJECTIVES: This study aimed to identify the pattern of post-operative drainage following partial superficial parotidectomy with and without the use of a bipolar vessel-sealing device. METHODS: Of the 49 patients undergoing parotidectomies, a bipolar vessel-sealing device was used for 20. Predictive factors included in the analysis were age, sex, body weight, operating time, tumour pathology, and diabetes mellitus, hypertension and smoking status. RESULTS: In multivariate analyses, body weight (p = 0.026) and non-use of a bipolar vessel-sealing device (p = 0.009) were significantly associated with increased post-operative drainage after 24 hours. There was also a trend towards increased drainage in diabetic patients. Operating times were significantly shorter in the bipolar vessel sealing device group. CONCLUSION: Although 24-hour drainage appears adequate for most patients, in obese and diabetic individuals there is a risk of requiring increased drainage. Therefore, the drain should be left in place for a longer period. The bipolar vessel-sealing device is safe and time-efficient, and decreases the post-operative drainage period. PMID- 26282395 TI - Rheumatic Diseases as the Fuel to Inflamm-aging. PMID- 26282394 TI - Intralesional injection of adipose-derived stem cells reduces hypertrophic scarring in a rabbit ear model. AB - INTRODUCTION: Redundant collagen deposition at sites of healing dermal wounds results in hypertrophic scars. Adipose-derived stem cells (ADSCs) exhibit promise in a variety of anti-fibrosis applications by attenuating collagen deposition. The objective of this study was to explore the influence of an intralesional injection of ADSCs on hypertrophic scar formation by using an established rabbit ear model. METHODS: Twelve New Zealand albino rabbits were equally divided into three groups, and six identical punch defects were made on each ear. On postoperative day 14 when all wounds were completely re-epithelialized, the first group received an intralesional injection of ADSCs on their right ears and Dulbecco's modified Eagle's medium (DMEM) on their left ears as an internal control. Rabbits in the second group were injected with conditioned medium of the ADSCs (ADSCs-CM) on their right ears and DMEM on their left ears as an internal control. Right ears of the third group remained untreated, and left ears received DMEM. We quantified scar hypertrophy by measuring the scar elevation index (SEI) on postoperative days 14, 21, 28, and 35 with ultrasonography. Wounds were harvested 35 days later for histomorphometric and gene expression analysis. RESULTS: Intralesional injections of ADSCs or ADSCs-CM both led to scars with a far more normal appearance and significantly decreased SEI (44.04 % and 32.48 %, respectively, both P <0.01) in the rabbit ears compared with their internal controls. Furthermore, we confirmed that collagen was organized more regularly and that there was a decreased expression of alpha-smooth muscle actin (alpha SMA) and collagen type Iota in the ADSC- and ADSCs-CM-injected scars according to histomorphometric and real-time quantitative polymerase chain reaction analysis. There was no difference between DMEM-injected and untreated scars. CONCLUSIONS: An intralesional injection of ADSCs reduces the formation of rabbit ear hypertrophic scars by decreasing the alpha-SMA and collagen type Iota gene expression and ameliorating collagen deposition and this may result in an effective and innovative anti-scarring therapy. PMID- 26282396 TI - Retraction Note to: Comprehensive gene expression analysis reveals multiple signal pathways associated with prostate cancer. PMID- 26282397 TI - Social housing conditions and oxytocin and vasopressin receptors contribute to ethanol conditioned social preference in female mice. AB - Social behavior modulates response to alcohol. Because oxytocin (OXT) and vasopressin (AVP) contribute to rewarding social behavior, the present study utilized a genetic strategy to determine whether OXT and AVP receptors (OXTR, AVPR1a) are essential for female mice to demonstrate a conditioned social preference for ethanol. The study compared wild-type (WT) and knock-out (KO) females lacking either Oxtr or Avpr1a in a conditioned social preference (CSP) test. KO females and WT females from Het-Het crosses were pair-housed: KO and WT(ko). WT females from Het-WT crosses were pair-housed: WT(wt). Test mice received 2g/kg ethanol or saline ip, and were paired four times each with one stimulus female (CS-) after saline, and with another female (CS+) following ethanol. After pairing, the time spent with CS+ and CS- females was measured. WT(wt) females showed conditioned preference for the CS+ female paired with ethanol, demonstrated by greater interaction time (p<0.05). In both KO lines, ethanol significantly reduced interaction with the CS+ female (p<0.05), and there was no change in interaction for WT(ko) females. Response to odors by habituation dishabituation was unaffected in both KO lines, and the response to a hypnotic dose of ethanol also was the same as in WT mice. However, anxiety, measured as time on the open arms of the elevated plus maze, was reduced in KO(Oxtr) females compared with WT(wt). The results suggest that Oxtr and Avpr1a are required for conditioned effects of an ethanol-associated social stimulus. The lack of CSP in WT(ko) females suggests that the quality of social interactions during postnatal and postweaning life may modulate development and expression of normal social responses. PMID- 26282398 TI - EPS8L2 is a new causal gene for childhood onset autosomal recessive progressive hearing loss. AB - BACKGROUND: More than 70 % of the cases of congenital deafness are of genetic origin, of which approximately 80 % are non-syndromic and show autosomal recessive transmission (DFNB forms). To date, 60 DFNB genes have been identified, most of which cause congenital, severe to profound deafness, whereas a few cause delayed progressive deafness in childhood. We report the study of two Algerian siblings born to consanguineous parents, and affected by progressive hearing loss. METHOD: After exclusion of GJB2 (the gene most frequently involved in non syndromic deafness in Mediterranean countries), we performed whole-exome sequencing in one sibling. RESULTS: A frame-shift variant (c.1014delC; p.Ser339Alafs*15) was identified in EPS8L2, encoding Epidermal growth factor receptor Pathway Substrate 8 L2, a protein of hair cells' stereocilia previously implicated in progressive deafness in the mouse. This variant predicts a truncated, inactive protein, or no protein at all owing to nonsense-mediated mRNA decay. It was detected at the homozygous state in the two clinically affected siblings, and at the heterozygous state in the unaffected parents and one unaffected sibling, whereas it was never found in a control population of 150 Algerians with normal hearing or in the Exome Variant Server database. CONCLUSION: Whole-exome sequencing allowed us to identify a new gene responsible for childhood progressive hearing loss transmitted on the autosomal recessive mode. PMID- 26282399 TI - Experiences with workflows for automating data-intensive bioinformatics. AB - High-throughput technologies, such as next-generation sequencing, have turned molecular biology into a data-intensive discipline, requiring bioinformaticians to use high-performance computing resources and carry out data management and analysis tasks on large scale. Workflow systems can be useful to simplify construction of analysis pipelines that automate tasks, support reproducibility and provide measures for fault-tolerance. However, workflow systems can incur significant development and administration overhead so bioinformatics pipelines are often still built without them. We present the experiences with workflows and workflow systems within the bioinformatics community participating in a series of hackathons and workshops of the EU COST action SeqAhead. The organizations are working on similar problems, but we have addressed them with different strategies and solutions. This fragmentation of efforts is inefficient and leads to redundant and incompatible solutions. Based on our experiences we define a set of recommendations for future systems to enable efficient yet simple bioinformatics workflow construction and execution. PMID- 26282401 TI - Adiponectin and leptin gene polymorphisms in patients with post-transplant diabetes mellitus. AB - BACKGROUND: Post-transplant diabetes mellitus (PTDM) is a common metabolic complication after organ transplantation and may be associated with the use of calcineurin inhibitors (tacrolimus and cyclosporine). Leptin and adiponectin are adipokines and play an important role in the regulation of insulin secretion as well as glucose and lipid metabolism. AIM: The aim of this study was to examine the association between adiponectin and leptin gene polymorphisms and development of PTDM. MATERIALS & METHODS: The study included 323 patients who received kidney transplants and were treated with calcineurin inhibitors (tacrolimus or cyclosporine). RESULTS: The association between adiponectin and leptin gene polymorphisms and PTDM was studied in three models of Cox regression analysis- additive, dominant and recessive. In these three models, the LEP rs2167270 gene polymorphism was statistically significantly associated with increased risk of PTDM. The association between the LEP rs2167270 polymorphism and PTDM was confirmed by multivariate regression analysis. CONCLUSION: The results of our study suggest an association between the leptin rs2167270 gene A allele and PTDM. Original submitted 27 February 2015; Revision submitted 22 May 2015. PMID- 26282403 TI - Mentorship: an unspoken obligation. PMID- 26282400 TI - Harmful practices in the management of childhood diarrhea in low- and middle income countries: a systematic review. AB - BACKGROUND: Harmful practices in the management of childhood diarrhea are associated with negative health outcomes, and conflict with WHO treatment guidelines. These practices include restriction of fluids, breast milk and/or food intake during diarrhea episodes, and incorrect use of modern medicines. We conducted a systematic review of English-language literature published since 1990 to assess the documented prevalence of these four harmful practices, and beliefs, motivations, and contextual factors associated with harmful practices in low- and middle-income countries. METHODS: We electronically searched PubMed, Embase, Ovid Global Health, and the WHO Global Health Library. Publications reporting the prevalence or substantive findings on beliefs, motivations, or context related to at least one of the four harmful practices were included, regardless of study design or representativeness of the sample population. RESULTS: Of the 114 articles included in the review, 79 reported the prevalence of at least one harmful practice and 35 studies reported on beliefs, motivations, or context for harmful practices. Most studies relied on sub-national population samples and many were limited to small sample sizes. Study design, study population, and definition of harmful practices varied across studies. Reported prevalence of harmful practices varied greatly across study populations, and we were unable to identify clearly defined patterns across regions, countries, or time periods. Caregivers reported that diarrhea management practices were based on the advice of others (health workers, relatives, community members), as well as their own observations or understanding of the efficacy of certain treatments for diarrhea. Others reported following traditionally held beliefs on the causes and cures for specific diarrheal diseases. CONCLUSIONS: Available evidence suggests that harmful practices in diarrhea treatment are common in some countries with a high burden of diarrhea-related mortality. These practices can reduce correct management of diarrheal disease in children and result in treatment failure, sustained nutritional deficits, and increased diarrhea mortality. The lack of consistency in sampling, measurement, and reporting identified in this literature review highlights the need to document harmful practices using standard methods of measurement and reporting for the continued reduction of diarrhea mortality. PMID- 26282404 TI - Bottom-up synthesis of high-performance nitrogen-enriched transition metal/graphene oxygen reduction electrocatalysts both in alkaline and acidic solution. AB - Oxygen reduction electrocatalysts with low cost and excellent performance are urgently required for large-scale application in fuel cells and metal-air batteries. Though nitrogen-enriched transition metal/graphene hybrids (N-TM/G, TM = Fe, Co, and Ni and related compounds) have been developed as novel substitutes for precious metal catalysts (PMCs) towards oxygen reduction reaction (ORR), a significant challenge still remains for simple and efficient synthesis of N-TM/G catalysts with satisfactory electrocatalytic behavior. Herein, we demonstrate a universal bottom-up strategy for efficient fabrication of strongly-coupled N-TM/G catalysts. This strategy is implemented via direct polymerization of transition metal phthalocyanine (TMPc) in the two-dimensional confined space of in situ generated g-C3N4 and a subsequent pyrolysis. Such a space-confined bottom-up synthesis route successfully constructs a strongly-coupled triple junction of transition metal-graphitic carbon-nitrogen-doped graphene (TM-GC-NG) with extensive controllability over the specific surface area, nitrogen content/types as well as the states of metal. As a result, the optimized N-Fe/G materials have promising potential as high-performance NPMCs towards ORR both in alkaline and acidic solution. PMID- 26282405 TI - Genetic diversity and genetic structure of the Siberian roe deer (Capreolus pygargus) populations from Asia. AB - BACKGROUND: The roe deer, Capreolus sp., is one of the most widespread meso mammals of Palearctic distribution, and includes two species, the European roe deer, C. capreolus inhabiting mainly Europe, and the Siberian roe deer, C. pygargus, distributed throughout continental Asia. Although there are a number of genetic studies concerning European roe deer, the Siberian roe deer has been studied less, and none of these studies use microsatellite markers. Natural processes have led to genetic structuring in wild populations. To understand how these factors have affected genetic structure and connectivity of Siberian roe deer, we investigated variability at 12 microsatellite loci for Siberian roe deer from ten localities in Asia. RESULTS: Moderate levels of genetic diversity (H(E) = 0.522 to 0.628) were found in all populations except in Jeju Island, South Korea, where the diversity was lowest (H(E) = 0.386). Western populations showed relatively low genetic diversity and higher degrees of genetic differentiation compared with eastern populations (mean Ar = 3.54 (east), 2.81 (west), mean F(ST) = 0.122). Bayesian-based clustering analysis revealed the existence of three genetically distinct groups (clusters) for Siberian roe deer, which comprise of the Southeastern group (Mainland Korea, Russian Far East, Trans-Baikal region and Northern part of Mongolia), Northwestern group (Western Siberia and Ural in Russia) and Jeju Island population. Genetic analyses including AMOVA (F(RT) = 0.200), Barrier and PCA also supported genetic differentiation among regions separated primarily by major mountain ridges, suggesting that mountains played a role in the genetic differentiation of Siberian roe deer. On the other hand, genetic evidence also suggests an ongoing migration that may facilitate genetic admixture at the border areas between two groups. CONCLUSIONS: Our results reveal an apparent pattern of genetic differentiation among populations inhabiting Asia, showing moderate levels of genetic diversity with an east-west gradient. The results suggest at least three distinct management units of roe deer in continental Asia, although genetic admixture is evident in some border areas. The insights obtained from this study shed light on management of Siberian roe deer in Asia and may be applied in conservation of local populations of Siberian roe deer. PMID- 26282406 TI - Activity of the DNA minor groove cross-linking agent SG2000 (SJG-136) against canine tumours. AB - BACKGROUND: Cancer is the leading cause of death in older dogs and its prevalence is increasing. There is clearly a need to develop more effective anti-cancer drugs in dogs. SG2000 (SJG-136) is a sequence selective DNA minor groove cross linking agent. Based on its in vitro potency, the spectrum of in vivo and clinical activity against human tumours, and its tolerability in human patients, SG2000 has potential as a novel therapeutic against spontaneously occurring canine malignancies. RESULTS: In vitro cytotoxicity was assessed using SRB and MTT assays, and in vivo activity was assessed using canine tumour xenografts. DNA interstrand cross-linking (ICL) was determined using a modification of the single cell gel electrophoresis (comet) assay. Effects on cell cycle distribution were assessed by flow cytometry and measurement of gamma-H2AX by immunofluorescence and immunohistochemistry. SG2000 had a multi-log differential cytotoxic profile against a panel of 12 canine tumour cell lines representing a range of common tumour types in dogs. In the CMeC-1 melanoma cell line, DNA ICLs increased linearly with dose following a 1 h treatment. Peak ICL was achieved within 1 h and no removal was observed over 48 h. A relationship between DNA ICL formation and cytotoxicity was observed across cell lines. The formation of gamma-H2AX foci was slow, becoming evident after 4 h and reaching a peak at 24 h. SG2000 exhibited significant anti-tumour activity against two canine melanoma tumour models in vivo. Anti-tumour activity was observed at 0.15 and 0.3 mg/kg given i.v. either once, or weekly x 3. Dose-dependent DNA ICL was observed in tumours (and to a lower level in peripheral blood mononuclear cells) at 2 h and persisted at 24 h. ICL increased following the second and third doses in a repeated dose schedule. At 24 h, dose dependent gamma-H2AX foci were more numerous than at 2 h, and greater in tumours than in peripheral blood mononuclear cells. SG2000-induced H2AX phosphorylation measured by immunohistochemistry showed good correspondence, but less sensitivity, than measurement of foci. CONCLUSIONS: SG2000 displayed potent activity in vitro against canine cancer cell lines as a result of the formation and persistence of DNA ICLs. SG2000 also had significant in vivo antitumour activity against canine melanoma xenografts, and the comet and gamma H2AX foci methods were relevant pharmacodynamic assays. The clinical testing of SG2000 against spontaneous canine cancer is warranted. PMID- 26282407 TI - Emtricitabine seminal plasma and blood plasma population pharmacokinetics in HIV infected men in the EVARIST ANRS-EP 49 study. AB - We aimed to describe blood plasma (BP) and seminal plasma (SP) pharmacokinetics of emtricitabine (FTC) in HIV-1-infected men, assess its penetration in the male genital tract, and evaluate its impact on seminal plasma HIV load (spVL) detection. Men from the EVARIST ANRS EP49 study receiving combined antiretroviral therapy with FTC and with suppressed BP viral load were included in the study. A total of 236 and 209 FTC BP and SP concentrations, respectively, were available. A population pharmacokinetic model was developed with Monolix 4.1.4. The impact of FTC seminal exposure on spVL detection was explored by receiver operating characteristic (ROC) curves and mixed-effects logistic regressions. FTC BP pharmacokinetics was described by a two-compartment model. The addition of an effect compartment with different input and output constants best described FTC SP pharmacokinetics. No covariates were found to explain the variability in SP. FTC exposures (area under the concentration-time curve from 0 to 24 h [AUC0-24]) were higher in SP than in BP (median AUC0-24, 38.04 and 12.95 mg . liter(-1) . h, respectively). The median (range) SP-to-BP AUC0-24 ratio was 2.91 (0.84 to 10.08). Less than 1% of FTC AUC0-24 ratios were lower than 1. The impact of FTC SP AUC0-24 or FTC SP-to-BP AUC0-24 ratio on spVL detection was not significant (P = 0.943 or 0.893, respectively). This is the first population model describing FTC pharmacokinetics simultaneously in both BP and SP. FTC distributes well in the male genital tract with higher FTC concentrations in SP than in BP. FTC seminal plasma exposures were considered efficient in the majority of men. PMID- 26282408 TI - Loss of hypermucoviscosity and increased fitness cost in colistin-resistant Klebsiella pneumoniae sequence type 23 strains. AB - In this study, we investigated the effects of colistin resistance on virulence and fitness in hypermucoviscous (HV) Klebsiella pneumoniae sequence type 23 (ST23) strains. Colistin-resistant mutants were developed from three colistin susceptible HV K. pneumoniae ST23 strains. The lipid A structures of strains were analyzed by matrix-assisted laser desorption ionization-time of flight (MALDI TOF) mass spectrometry. Changes in HV were investigated using the string test, and extracellular polysaccharide production was quantified. The expression levels of the phoQ, pmrD, pmrB, pbgP, magA, and p-rmpA2 genes, serum resistance, and biofilm-forming activity were determined. The fitness of colistin-resistant mutants compared to that of the parental strains was examined by determining the competitive index (CI). The colistin-resistant mutants exhibited reduced HV, which was accompanied by decreased formation of capsular polysaccharides (CPS) and reduced expression of genes (magA and p-rmpA2). While there was enhanced expression of pmrD and pbgP in all colistin-resistant derivatives, there were differences in the expression levels of phoQ and pmrB between strains. MALDI-TOF analysis detected the addition of aminoarabinose or palmitate to the lipid A moiety of lipopolysaccharide in the colistin-resistant derivatives. In addition, survival rates in the presence of normal human serum were decreased in the mutant strains, and CI values (0.01 to 0.19) indicated significant fitness defects in the colistin-resistant derivatives compared to the respective parental strains. In hypervirulent HV K. pneumoniae strains, the acquisition of colistin resistance was accompanied by reduced CPS production, impaired virulence, and a significant fitness cost. PMID- 26282409 TI - Ceftolozane-tazobactam activity against phylogenetically diverse Clostridium difficile strains. AB - Ceftolozane-tazobactam (C/T) is approved for the treatment of complicated intra abdominal and urinary tract infections and has varied activity against anaerobic bacteria. Here, we evaluate the activity of C/T against a phylogenetically diverse collection of Clostridium difficile isolates and report uniformly high MICs (>=256 MUg/ml) to C/T. PMID- 26282410 TI - Outbreak caused by Enterobacteriaceae harboring NDM-1 metallo-beta-lactamase carried in an IncFII plasmid in a tertiary care hospital in Mexico City. AB - Carbapenem-resistant Enterobacteriaceae carrying New Delhi metallo-beta-lactamase 1 (NDM-1) have rarely been reported in Latin America. We report of an outbreak caused by a blaNDM-1-harboring plasmid spread through different bacterial species, including Escherichia coli (ST617) and Enterobacter cloacae (ST182) isolates from the same patient and three Klebsiella pneumoniae isolates (ST22) derived from three epidemiologically related patients. IncFII plasmids were found in all strains. Measures to control the outbreak were applied successfully. PMID- 26282411 TI - Darunavir and ritonavir total and unbound plasmatic concentrations in HIV-HCV coinfected patients with hepatic cirrhosis compared to those in HIV-monoinfected patients. AB - Our objective was to describe the pharmacokinetic (PK) parameters of total and unbound darunavir and ritonavir concentrations in HIV-hepatitis C virus (HCV) coinfected patients with cirrhosis, as ritonavir-boosted darunavir is mainly metabolized in the liver, and hepatic cirrhosis might modify darunavir-ritonavir concentrations. This was a prospective, case-control, and unicenter study. HIV HCV-coinfected patients with compensated cirrhosis (cases) and HIV-monoinfected patients with normal liver function (controls) were included. Darunavir-ritonavir was given at 800/100 mg once daily. Patients were followed for 24 weeks to assess safety and efficacy. A steady-state 12-h PK study was performed. Total and unbound concentrations were determined by liquid chromatography-tandem mass spectrometry. The unbound fraction was obtained by ultrafiltration. The plasma area under the concentration-time curve (AUC) and oral clearance (CL/F) were assessed by noncompartmental models. Thirty patients (20 cases and 10 controls) were included. Among cirrhotic patients, the Child-Pugh score was C in 4 cases, B in 1 case, and A in 15 cases; the median (interquartile range) transient elastography values were 20 kPa (14 to 26 kPa), and 5 patients had prior clinical decompensations. There were no significant differences in the darunavir PK parameters between cases and controls except for longer time to maximum plasma concentrations (Tmax) and half-lives in the cirrhotic patients. There were no significant differences in ritonavir total concentrations, but the unbound concentrations were higher in cirrhotic patients. There were significant correlations between the darunavir total and unbound concentrations in both cirrhotic patients and controls. There were no differences in PK parameters based on Child-Pugh score, liver elasticity, gender, or use of concomitant medications. In conclusion, in HIV-HCV-coinfected patients with clinically compensated cirrhosis receiving darunavir-ritonavir at 800/100 mg once daily, the darunavir total and unbound concentrations are similar to those observed in noncirrhotic patients, and dose adjustments are not necessary. PMID- 26282412 TI - Population pharmacokinetic analysis of isoniazid, acetylisoniazid, and isonicotinic acid in healthy volunteers. AB - In this study, we aimed to quantify the effects of the N-acetyltransferase 2 (NAT2) phenotype on isoniazid (INH) metabolism in vivo and identify other sources of pharmacokinetic variability following single-dose administration in healthy Asian adults. The concentrations of INH and its metabolites acetylisoniazid (AcINH) and isonicotinic acid (INA) in plasma were evaluated in 33 healthy Asians who were also given efavirenz and rifampin. The pharmacokinetics of INH, AcINH, and INA were analyzed using nonlinear mixed-effects modeling (NONMEM) to estimate the population pharmacokinetic parameters and evaluate the relationships between the parameters and the elimination status (fast, intermediate, and slow acetylators), demographic status, and measures of renal and hepatic function. A two-compartment model with first-order absorption best described the INH pharmacokinetics. AcINH and INA data were best described by a two- and a one compartment model, respectively, linked to the INH model. In the final model for INH, the derived metabolic phenotypes for NAT2 were identified as a significant covariate in the INH clearance, reducing its interindividual variability from 86% to 14%. The INH clearance in fast eliminators was 1.9- and 7.7-fold higher than in intermediate and slow eliminators, respectively (65 versus 35 and 8 liters/h). Creatinine clearance was confirmed as a significant covariate for AcINH clearance. Simulations suggested that the current dosing guidelines (200 mg for 30 to 45 kg and 300 mg for >45 kg) may be suboptimal (3 mg/liter <= Cmax <= 6 mg/liter) irrespective of the acetylator class. The analysis established a model that adequately characterizes INH, AcINH, and INA pharmacokinetics in healthy Asians. Our results refine the NAT2 phenotype-based predictions of the pharmacokinetics for INH. PMID- 26282413 TI - Ethanol and isopropanol in concentrations present in hand sanitizers sharply reduce excystation of Giardia and Entamoeba and eliminate oral infectivity of Giardia cysts in gerbils. AB - Enteric protozoan parasites, which are spread by the fecal-oral route, are important causes of diarrhea (Giardia duodenalis) and amebic dysentery (Entamoeba histolytica). Cyst walls of Giardia and Entamoeba have a single layer composed of fibrils of beta-1,3-linked GalNAc and beta-1,4-linked GlcNAc (chitin), respectively. The goal here was to determine whether hand sanitizers that contain ethanol or isopropanol as the active microbicide might reduce transmission of these parasites. We found that treatment with these alcohols with or without drying in a rotary evaporator (to model rapid evaporation of sanitizers on hands) kills 85 to 100% of cysts of G. duodenalis and 90 to 100% of cysts of Entamoeba invadens (a nonpathogenic model for E. histolytica), as shown by nuclear labeling with propidium iodide and failure to excyst in vitro. Alcohols with or without drying collapsed the cyst walls of Giardia but did not collapse the cyst walls of Entamoeba. To validate the in vitro results, we showed that treatment with alcohols eliminated oral infection of gerbils by 1,000 G. duodenalis cysts, while a commercial hand sanitizer (Purell) killed E. invadens cysts that were directly applied to the hands. These results suggest that expanded use of alcohol-based hand sanitizers might reduce the transmission of Giardia and Entamoeba. PMID- 26282414 TI - Characterization of the global stabilizing substitution A77V and its role in the evolution of CTX-M beta-lactamases. AB - The widespread use of oxyimino-cephalosporin antibiotics drives the evolution of the CTX-M family of beta-lactamases that hydrolyze these drugs and confer antibiotic resistance. Clinically isolated CTX-M enzymes carrying the P167S or D240G active site-associated adaptive mutation have a broadened substrate profile that includes the oxyimino-cephalosporin antibiotic ceftazidime. The D240G substitution is known to reduce the stability of CTX-M-14 beta-lactamase, and the P167S substitution is shown here to also destabilize the enzyme. Proteins are marginally stable entities, and second-site mutations that stabilize the enzyme can offset a loss in stability caused by mutations that enhance enzyme activity. Therefore, the evolution of antibiotic resistance enzymes can be dependent on the acquisition of stabilizing mutations. The A77V substitution is present in CTX-M extended-spectrum beta-lactamases (ESBLs) from a number of clinical isolates, suggesting that it may be important in the evolution of antibiotic resistance in this family of beta-lactamases. In this study, the effects of the A77V substitution in the CTX-M-14 model enzyme were characterized with regard to the kinetic parameters for antibiotic hydrolysis as well as enzyme expression levels in vivo and protein stability in vitro. The A77V substitution has little effect on the kinetics of oxyimino-cephalosporin hydrolysis, but it stabilizes the CTX-M enzyme and compensates for the loss of stability resulting from the P167S and D240G mutations. The acquisition of global stabilizing mutations, such as A77V, is an important feature in beta-lactamase evolution and a common mechanism in protein evolution. PMID- 26282415 TI - Effects of selection pressure and genetic association on the relationship between antibiotic resistance and virulence in Escherichia coli. AB - Antibiotic selection pressure and genetic associations may lead to the cooccurrence of resistance and virulence in individual pathogens. However, there is a lack of rigorous epidemiological evidence that demonstrates the cooccurrence of resistance and virulence at the population level. Using samples from a population-based case-control study in 25 villages in rural Ecuador, we characterized resistance to 12 antibiotics among pathogenic (n = 86) and commensal (n = 761) Escherichia coli isolates, classified by the presence or absence of known diarrheagenic virulence factor genes. The prevalences of resistance to single and multiple antibiotics were significantly higher for pathogenic isolates than for commensal isolates. Using a generalized estimating equation, antibiotic resistance was independently associated with virulence factor carriage, case status, and antibiotic use (for these respective factors: odds ratio [OR] = 3.0, with a 95% confidence interval [CI] of 1.7 to 5.1; OR = 2.0, with a 95% CI of 1.3 to 3.0; and OR = 1.5, with a 95% CI of 0.9 to 2.5). Virulence factor carriage was more strongly related to antibiotic resistance than antibiotic use for all antibiotics examined, with the exception of fluoroquinolones, gentamicin, and cefotaxime. This study provides epidemiological evidence that antibiotic resistance and virulence factor carriage are linked in E. coli populations in a community setting. Further, these data suggest that while the cooccurrence of resistance and virulence in E. coli is partially due to antibiotic selection pressure, it is also genetically determined. These findings should be considered in developing strategies for treating infections and controlling for antibiotic resistance. PMID- 26282416 TI - Lack of mutational hot spots during decitabine-mediated HIV-1 mutagenesis. AB - Decitabine has previously been shown to induce lethal mutagenesis of human immunodeficiency virus type 1 (HIV-1). However, the factors that determine the susceptibilities of individual sequence positions in HIV-1 to decitabine have not yet been defined. To investigate this, we performed Illumina high-throughput sequencing of multiple amplicons prepared from proviral DNA that was recovered from decitabine-treated cells infected with HIV-1. We found that decitabine induced an ~4.1-fold increase in the total mutation frequency of HIV-1, primarily due to a striking ~155-fold increase in the G-to-C transversion frequency. Intriguingly, decitabine also led to an ~29-fold increase in the C-to-G transversion frequency. G-to-C frequencies varied substantially (up to ~80-fold) depending upon sequence position, but surprisingly, mutational hot spots (defined as upper outliers within the mutation frequency distribution) were not observed. We further found that every single guanine position examined was significantly susceptible to the mutagenic effects of decitabine. Taken together, these observations demonstrate for the first time that decitabine-mediated HIV-1 mutagenesis is promiscuous and occurs in the absence of a clear bias for mutational hot spots. These data imply that decitabine-mediated G-to-C mutagenesis is a highly effective antiviral mechanism for extinguishing HIV-1 infectivity. PMID- 26282417 TI - Emergence of TR46/Y121F/T289A in an Aspergillus fumigatus isolate from a Chinese patient. PMID- 26282418 TI - Hepatitis C virus genotype 4 resistance and subtype demographic characterization of patients treated with ombitasvir plus paritaprevir/ritonavir. AB - Hepatitis C virus (HCV) genotype 4 (GT4) is genetically diverse, with 17 confirmed subtypes, and comprises approximately 13% of infections worldwide. In this study, we identified GT4 subtypes by phylogenetic analysis, assessed differences in patient demographics across GT4 subtypes, examined baseline sequence variability among subtypes and the potential impact on treatment outcome, and analyzed the development of viral resistance in patients who received a regimen of ombitasvir (nonstructural protein 5A [NS5A] inhibitor) plus ritonavir-boosted paritaprevir (NS3/4A inhibitor) with or without ribavirin (RBV) for the treatment of HCV GT4 infection. Phylogenetic analysis of HCV NS3/4A, NS5A, and NS5B nucleotide sequences identified 7 subtypes (4a, 4b, 4c, 4d, 4f, 4g/4k, and 4o) among 132 patient samples. Subtype prevalence varied by country, and the distributions of patient birth cohort and race were significantly different across GT4 subtypes 4a, 4d, and non-4a/4d. Baseline amino acid variability was detected in NS5A across GT4 subtypes but had no impact on treatment outcome. Three patients experienced virologic failure and were infected with subtype 4d, and the predominant resistance-associated variants at the time of failure were D168V in NS3 and L28V in NS5A. Overall, high response rates were observed among patients infected with 7 HCV GT4 subtypes, with no impact of baseline variants on treatment outcome. GT4 subtype distribution in this study differed based on patient demographics and geography. PMID- 26282419 TI - Investigating clinically adequate concentrations of oseltamivir carboxylate in end-stage renal disease patients undergoing hemodialysis using a population pharmacokinetic approach. AB - End-stage renal disease (ESRD) patients receiving hemodialysis (HD) are at heightened risk for influenza, but the optimal oseltamivir dosage regimen for treating or preventing influenza in this high-risk population is still uncertain. Pharmacokinetic data for 24 adults with ESRD were pooled from a single-dose and a multiple-dose study to develop a population pharmacokinetic model using nonlinear mixed-effects modeling. The final model comprised five compartments, two each to describe the systemic pharmacokinetics of oseltamivir phosphate and its metabolite, oseltamivir carboxylate (OC), and a delay compartment to describe oseltamivir metabolism. Estimated OC clearance in the model was markedly faster during HD sessions (7.43 liters/min) than at other times (0.19 liter/min). Model simulations showed that 30 mg oseltamivir given after every HD session is the most suitable regimen for influenza treatment, producing trough OC concentrations above the median value achieved with the 75-mg twice-daily regimen in patients with normal renal function and peak concentrations below the highest oseltamivir exposures known to be well tolerated (median exposures after twice-daily dosing of 450 mg). Administration of the first dose following diagnosis of influenza need not wait until after the next HD session: addition of a single 30-mg dose during the 12 h before the next HD session raises OC exposures quickly without posing any safety risk. Further simulation showed that 30 mg oseltamivir given after every other HD session is the most suitable regimen for influenza prophylaxis. PMID- 26282420 TI - Population pharmacokinetics of peramivir in healthy volunteers and influenza patients. AB - Peramivir is an intravenous anti-influenza agent that inhibits viral growth by selectively inhibiting neuraminidase in human influenza A and B viruses. To characterize its pharmacokinetics, a population pharmacokinetic analysis of peramivir was performed using 3,199 plasma concentration data samples from 332 subjects in six clinical studies in Japan and the United States, including studies with renal impairment subjects, elderly subjects, and influenza patients. A three-compartment model well described the plasma concentration data for peramivir, and creatinine clearance was found to be the most important factor influencing clearance. Age and body weight were also found to be covariates for clearance and the volume of distribution, respectively. No difference in pharmacokinetics was found between genders or between Japanese and U.S. SUBJECTS: Small differences in pharmacokinetics were observed between uninfected subjects and influenza patients (clearance was 18% higher and the volume of distribution was 6% lower in influenza patients). Monte Carlo simulations indicated that single adjusted doses of 1/3- and 1/6-fold for patients with moderate and severe renal impairment, respectively, would give areas under the curve comparable to those for patients with normal renal function. The population pharmacokinetic model developed for peramivir should be useful for understanding its pharmacokinetic characteristics and for dose adjustment on the basis of renal function. PMID- 26282421 TI - IMP-51, a novel IMP-type metallo-beta-lactamase with increased doripenem- and meropenem-hydrolyzing activities, in a carbapenem-resistant Pseudomonas aeruginosa clinical isolate. AB - A meropenem-resistant Pseudomonas aeruginosa isolate was obtained from a patient in a medical setting in Hanoi, Vietnam. The isolate was found to have a novel IMP type metallo-beta-lactamase, IMP-51, which differed from IMP-7 by an amino acid substitution (Ser262Gly). Escherichia coli expressing blaIMP-51 showed greater resistance to cefoxitin, meropenem, and moxalactam than E. coli expressing blaIMP 7. The amino acid residue at position 262 was located near the active site, proximal to the H263 Zn(II) ligand. PMID- 26282422 TI - Emergence of Raoultella ornithinolytica coproducing IMP-4 and KPC-2 carbapenemases in China. AB - We report here the emergence of seven IMP-4-producing Raoultella ornithinolytica isolates obtained from one patient. All isolates carried the blaIMP-4 carbapenemase gene, five isolates also carried blaSHV-12, four contained blaTEM 1, and one contained blaOXA-1. Notably, the R. ornithinolytica isolate Ro25724 also expressed Klebsiella pneumoniae carbapenemase (KPC)-2. The blaKPC-2 gene was located on a Tn3-Tn4401 integration structure on a plasmid of ~450 kb. This is the first description of the coexistence of blaKPC-2 and blaIMP-4 from the genus Raoultella. PMID- 26282423 TI - Case-control study and case series of pseudohyperphosphatemia during exposure to liposomal amphotericin B. AB - Pseudohyperphosphatemia due to an interaction between liposomal amphotericin B and the Beckman Coulter PHOSm assay occurs sporadically and remains underrecognized in clinical practice. This retrospective case-control study compares the incidences of hyperphosphatemia in adult inpatients exposed to liposomal amphotericin B or a triazole. A case series of patients with confirmed pseudohyperphosphatemia is described. A total of 80 exposures to liposomal amphotericin B and 726 exposures to triazoles were identified. Among subjects without chronic kidney disease and no concomitant acute kidney injury, hyperphosphatemia occurred more often during liposomal amphotericin B therapy than during triazole therapy (40% [14/35 cases] versus 10% [47/475 cases] of cases; P < 0.01; adjusted odds ratio, 5.2 [95% confidence interval {CI}, 2.3 to 11.9]). Among individuals with chronic kidney disease and no concomitant acute kidney injury, hyperphosphatemia also occurred more often during liposomal amphotericin B exposure (59% [10/17 cases] versus 20% [34/172 cases] of cases; P < 0.01; adjusted odds ratio, 6.0 [95% CI, 2.0 to 18.0]). When acute kidney injury occurred during antifungal exposure, the frequencies of hyperphosphatemia were not different between treatments. Seven episodes of unexpected hyperphosphatemia during liposomal amphotericin B exposure prompted a confirmatory test using an endpoint-based assay that found lower serum phosphorus levels (median difference of 2.5 mg/dl [range, 0.6 to 3.6 mg/dl]). Liposomal amphotericin B exposure confers a higher likelihood of developing hyperphosphatemia than that with exposure to a triazole antifungal, which is likely attributable to pseudohyperphosphatemia. Elevated phosphorus levels in patients receiving liposomal amphotericin B at institutions using the Beckman Coulter PHOSm assay should be interpreted cautiously. PMID- 26282424 TI - Functional analysis of a bacitracin resistance determinant located on ICECp1, a novel Tn916-like element from a conjugative plasmid in Clostridium perfringens. AB - Bacitracins are mixtures of structurally related cyclic polypeptides with antibiotic properties. They act by interfering with the biosynthesis of the bacterial cell wall. In this study, we analyzed an avian necrotic enteritis strain of Clostridium perfringens that was resistant to bacitracin and produced NetB toxin. We identified a bacitracin resistance locus that resembled a bacitracin resistance determinant from Enterococcus faecalis. It contained the structural genes bcrABD and a putative regulatory gene, bcrR. Mutagenesis studies provided evidence that both bcrA and bcrB are essential for bacitracin resistance, and that evidence was supported by the results of experiments in which the introduction of both the bcrA and bcrB genes into a bacitracin susceptible C. perfringens strain was required to confer bacitracin resistance. The wild-type strain was shown to contain at least three large, putatively conjugative plasmids, and the bcrRABD locus was localized to an 89.7-kb plasmid, pJIR4150. This plasmid was experimentally shown to be conjugative and was sequenced. The sequence revealed that it also carries a tpeL toxin gene and is related to the pCW3 family of conjugative antibiotic resistance and toxin plasmids from C. perfringens. The bcr genes were located on a genetic element, ICECp1, which is related to the Tn916 family of integrative conjugative elements (ICEs). ICECp1 appears to be the first Tn916-like element shown to confer bacitracin resistance. In summary, we identified in a toxin-producing C. perfringens strain a novel mobile bacitracin resistance element which was experimentally shown to be essential for bacitracin resistance and is carried by a putative ICE located on a conjugative plasmid. PMID- 26282425 TI - HIV drug resistance testing by high-multiplex "wide" sequencing on the MiSeq instrument. AB - Limited access to HIV drug resistance testing in low- and middle-income countries impedes clinical decision-making at the individual patient level. An efficient protocol to address this issue must be established to minimize negative therapeutic outcomes for HIV-1-infected individuals in such settings. This is an observational study to ascertain the potential of newer genomic sequencing platforms, such as the Illumina MiSeq instrument, to provide accurate HIV drug resistance genotypes for hundreds of samples simultaneously. Plasma samples were collected from Canadian patients during routine drug resistance testing (n = 759) and from a Ugandan study cohort (n = 349). Amplicons spanning HIV reverse transcriptase codons 90 to 234 were sequenced with both MiSeq sequencing and conventional Sanger sequencing methods. Sequences were evaluated for nucleotide concordance between methods, using coverage and mixture parameters for quality control. Consensus sequences were also analyzed for disparities in the identification of drug resistance mutations. Sanger and MiSeq sequencing was successful for 881 samples (80%) and 892 samples (81%), respectively, with 832 samples having results from both methods. Most failures were for samples with viral loads of <3.0 log10 HIV RNA copies/ml. Overall, 99.3% nucleotide concordance between methods was observed. MiSeq sequencing achieved 97.4% sensitivity and 99.3% specificity in detecting resistance mutations identified by Sanger sequencing. Findings suggest that the Illumina MiSeq platform can yield high-quality data with a high-multiplex "wide" sequencing approach. This strategy can be used for multiple HIV subtypes, demonstrating the potential for widespread individual testing and annual population surveillance in resource-limited settings. PMID- 26282426 TI - Optimizing the initial amikacin dosage in adults. AB - We report on the pharmacokinetics (PK) and pharmacodynamics (PD) of high-dose (>15 mg/kg of body weight per day) amikacin. A mean (standard deviation [SD]) maximum drug concentration in the serum (Cmax) and 24-h area under the concentration-time curve (AUC24) of 101 (49.4) mg/liter and 600 (387) mg . h/liter, respectively, were observed (n = 73) with 28.0 (8.47) mg/kg/day doses. An initial amikacin dose of 2,500 mg in adults weighing 40 kg to 200 kg with therapeutic drug monitoring to adjust the maintenance dose will optimize its PK and PD. PMID- 26282427 TI - Phospholipase A1 modulates the cell envelope phospholipid content of Brucella melitensis, contributing to polymyxin resistance and pathogenicity. AB - A subset of bacterial pathogens, including the zoonotic Brucella species, are highly resistant against polymyxin antibiotics. Bacterial polymyxin resistance has been attributed primarily to the modification of lipopolysaccharide; however, it is unknown what additional mechanisms mediate high-level resistance against this class of drugs. This work identified a role for the Brucella melitensis gene bveA (BMEII0681), encoding a predicted esterase, in the resistance of B. melitensis to polymyxin B. Characterization of the enzymatic activity of BveA demonstrated that it is a phospholipase A1 with specificity for phosphatidylethanolamine (PE). Further, lipidomic analysis of B. melitensis revealed an excess of PE lipids in the bacterial membranes isolated from the bveA mutant. These results suggest that by lowering the PE content of the cell envelope, BveA increases the resistance of B. melitensis to polymyxin B. BveA was required for survival and replication of B. melitensis in macrophages and for persistent infection in mice. BveA family esterases are encoded in the genomes of the alphaproteobacterial species that coexist with the polymyxin-producing bacteria in the rhizosphere, suggesting that maintenance of a low PE content in the bacterial cell envelope may be a shared persistence strategy for association with plant and mammalian hosts. PMID- 26282429 TI - The phosphoenolpyruvate:sugar phosphotransferase system is involved in sensitivity to the glucosylated bacteriocin sublancin. AB - The mode of action of a group of glycosylated antimicrobial peptides known as glycocins remains to be elucidated. In the current study of one glycocin, sublancin, we identified the phosphoenolpyruvate:sugar phosphotransferase system (PTS) of Bacillus species as a key player in bacterial sensitivity. Sublancin kills several Gram-positive bacteria, such as Bacillus species and Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). Unlike other classes of bacteriocins for which the PTS is involved in their mechanism of action, we show that the addition of PTS-requiring sugars leads to increased resistance rather than increased sensitivity, suggesting that sublancin has a distinct mechanism of action. Collectively, our present mutagenesis and genomic studies demonstrate that the histidine-containing phosphocarrier protein (HPr) and domain A of enzyme II (PtsG) in particular are critical determinants for bacterial sensitivity to sublancin. PMID- 26282428 TI - Multicenter study of epidemiological cutoff values and detection of resistance in Candida spp. to anidulafungin, caspofungin, and micafungin using the Sensititre YeastOne colorimetric method. AB - Neither breakpoints (BPs) nor epidemiological cutoff values (ECVs) have been established for Candida spp. with anidulafungin, caspofungin, and micafungin when using the Sensititre YeastOne (SYO) broth dilution colorimetric method. In addition, reference caspofungin MICs have so far proven to be unreliable. Candida species wild-type (WT) MIC distributions (for microorganisms in a species/drug combination with no detectable phenotypic resistance) were established for 6,007 Candida albicans, 186 C. dubliniensis, 3,188 C. glabrata complex, 119 C. guilliermondii, 493 C. krusei, 205 C. lusitaniae, 3,136 C. parapsilosis complex, and 1,016 C. tropicalis isolates. SYO MIC data gathered from 38 laboratories in Australia, Canada, Europe, Mexico, New Zealand, South Africa, and the United States were pooled to statistically define SYO ECVs. ECVs for anidulafungin, caspofungin, and micafungin encompassing >=97.5% of the statistically modeled population were, respectively, 0.12, 0.25, and 0.06 MUg/ml for C. albicans, 0.12, 0.25, and 0.03 MUg/ml for C. glabrata complex, 4, 2, and 4 MUg/ml for C. parapsilosis complex, 0.5, 0.25, and 0.06 MUg/ml for C. tropicalis, 0.25, 1, and 0.25 MUg/ml for C. krusei, 0.25, 1, and 0.12 MUg/ml for C. lusitaniae, 4, 2, and 2 MUg/ml for C. guilliermondii, and 0.25, 0.25, and 0.12 MUg/ml for C. dubliniensis. Species-specific SYO ECVs for anidulafungin, caspofungin, and micafungin correctly classified 72 (88.9%), 74 (91.4%), 76 (93.8%), respectively, of 81 Candida isolates with identified fks mutations. SYO ECVs may aid in detecting non-WT isolates with reduced susceptibility to anidulafungin, micafungin, and especially caspofungin, since testing the susceptibilities of Candida spp. to caspofungin by reference methodologies is not recommended. PMID- 26282430 TI - Targeting the parasite's DNA with methyltriazenyl purine analogs is a safe, selective, and efficacious antitrypanosomal strategy. AB - The human and veterinary disease complex known as African trypanosomiasis continues to inflict significant global morbidity, mortality, and economic hardship. Drug resistance and toxic side effects of old drugs call for novel and unorthodox strategies for new and safe treatment options. We designed methyltriazenyl purine prodrugs to be rapidly and selectively internalized by the parasite, after which they disintegrate into a nontoxic and naturally occurring purine nucleobase, a simple triazene-stabilizing group, and the active toxin: a methyldiazonium cation capable of damaging DNA by alkylation. We identified 2-(3 acetyl-3-methyltriazen-1-yl)-6-hydroxypurine (compound 1) as a new lead compound, which showed submicromolar potency against Trypanosoma brucei, with a selectivity index of >500, and it demonstrated a curative effect in animal models of acute trypanosomiasis. We investigated the mechanism of action of this lead compound and showed that this molecule has significantly higher affinity for parasites over mammalian nucleobase transporters, and it does not show cross-resistance with current first-line drugs. Once selectively accumulated inside the parasite, the prodrug releases a DNA-damaging methyldiazonium cation. We propose that ensuing futile cycles of attempted mismatch repair then lead to G2/M phase arrest and eventually cell death, as evidenced by the reduced efficacy of this purine analog against a mismatch repair-deficient (MSH2(-/-)) trypanosome cell line. The observed absence of genotoxicity, hepatotoxicity, and cytotoxicity against mammalian cells revitalizes the idea of pursuing parasite-selective DNA alkylators as a safe chemotherapeutic option for the treatment of human and animal trypanosomiasis. PMID- 26282431 TI - Interplay among membrane-bound lytic transglycosylase D1, the CreBC two-component regulatory system, the AmpNG-AmpDI-NagZ-AmpR regulatory circuit, and L1/L2 beta lactamase expression in Stenotrophomonas maltophilia. AB - Lytic transglycosylases (LTs) are an important class of enzymes involved in peptidoglycan (PG) cleavage, with the concomitant formation of an intramolecular 1,6-anhydromuramoyl reaction product. There are six annotated LT genes in the Stenotrophomonas maltophilia genome, including genes for five membrane-bound LTs (mltA, mltB1, mltB2, mltD1, and mltD2) and a gene for soluble LT (slt). Six LTs of S. maltophilia KJ were systematically mutated, yielding the DeltamltA, DeltamltB1, DeltamltB2, DeltamltD1, DeltamltD2, and Deltaslt mutants. Inactivation of mltD1 conferred a phenotype of elevated uninduced beta-lactamase activity. The underlying mechanism responsible for this phenotype was elucidated by the construction of several mutants and determination of beta-lactamase activity. The expression of the genes assayed was assessed by quantitative reverse transcriptase PCR and a promoter transcription fusion assay. The results demonstrate that DeltamltD1 mutant-mediated L1/L2 beta-lactamase expression involved the creBC two-component regulatory system (TCS) and the ampNG-ampDI-nagZ ampR regulatory circuit. The inactivation of mltD1 resulted in mltB1 and mltD2 upexpression in a creBC- and ampNG-dependent manner. The overexpressed MltB1 and MltD2 activity contributed to the expression of the L1/L2 beta-lactamase genes via the ampNG-ampDI-nagZ-ampR regulatory circuit. These findings reveal, for the first time, a linkage between LTs, the CreBC TCS, the ampNG-ampDI-nagZ-ampR regulatory circuit, and L1/L2 beta-lactamase expression in S. maltophilia. PMID- 26282433 TI - Conscious voiding during bladder obstruction in guinea pigs correlates with contractile activity of isolated bladders. AB - PURPOSE: There are many hypotheses accounting for detrusor overactivity; however, the exact mechanisms are still incompletely understood. We used a model of bladder outlet obstruction in male guinea pigs as a way to produce detrusor overactivity. The objective was to determine whether changes in voiding of obstructed guinea pigs correlates with specific changes in contractile activity of their isolated bladders in vitro. MATERIAL AND METHODS: Conscious voiding activity of sham-operated and obstructed animals was measured in metabolic cages. Contractile activity (spontaneous or evoked by distension, electrical field stimulation or cholinergic agonists) was recorded via a pressure transducer in the isolated bladders in vitro. RESULTS: The frequency of conscious voiding increased (while voiding volume decreased) in the obstructed group, compared with the sham-operated group, 4 weeks after surgical intervention. In comparison to the sham-operated animals, the bladders from the obstructed guinea pigs were enlarged and inflamed, their frequency of spontaneous contractions was higher, while the amplitudes of electrical field stimulation (EFS)-induced contractions and bladder compliance were lower. Changes in conscious voiding during obstruction were significantly associated with alterations in structural parameters (bladder weight, thickness and histological damage score) and functional contractile parameters (frequency of spontaneous contractions, amplitude of EFS-induced contractions and bladder compliance) of their isolated bladders. CONCLUSIONS: Our findings revealed significant association between conscious voiding and structural and contractile activity changes of the isolated bladders in obstruction. The data suggest that change in contractile activity of the bladder itself is a major contributor to obstruction-induced bladder overactivity. PMID- 26282432 TI - FrzA gene protects cardiomyocytes from H2O2-induced oxidative stress through restraining the Wnt/Frizzled pathway. AB - BACKGROUND: Lately, there is accumulating evidence that the Wnt/Frizzled pathway is reactivated after myocardial infarction, the inhibition of the pathway is beneficial since it reduce of myocardial apoptosis and prevents heart failure. FrzA/Sfrp-1, a secreted frizzled-related protein and antagonist for the wnt/frizzled pathway. We assessed the hypothesis that FrzA protects cardiomyocytes from H2O2-Induced Oxidative damage through the inhibition of Wnt/Frizzled pathway activity. METHODS: We used a recombinant AAV9 vector to deliver FrzA gene into neonatal rat ventricle myocytes and developed an oxidative stress model using H2O2. The cell vitality was measured by MTT colorimetric assay. Western blot and RT-PCR were used to evaluate the expressions of Dvl-1, beta-catenin, c-Myc, Bax and Bcl-2. Flow cytometry analysis of cardiomyocytes apoptosis. RESULTS: We confirmed that Wnt/frizzled pathway is involved in H2O2 induced apoptosis in cardiomyocytes. Compared with controls, H2O2 induced the upregulation of Dvl-1, beta-catenin, and c-Myc. FrzA suppressed the expression of Dvl-1, beta-catenin, c-Myc and the activity of the Wnt/frizzled pathway. Furthermore, FrzA over-expression decreased the apoptotic rate, and the Bax/Bcl-2 ratio in cardiomyocytes treated with H2O2. CONCLUSIONS: FrzA, through the inhibition of Wnt/Frizzled pathway activity reduced H2O2-induced cardiomyocytes apoptosis and could be a potential therapeutic target for prevention of cardiac oxidative damage. PMID- 26282434 TI - Melon Genome Study Reveals Recent Impacts of Breeding. PMID- 26282435 TI - A plasmonic nanosensor with inverse sensitivity for circulating cell-free DNA quantification. AB - A plasmonic nanosensor (using gold nanorods) with inverse sensitivity is presented for circulating cell-free DNA quantification. The inverse sensitivity (i.e. the lower the analyte concentration, the higher the response intensity) is achieved by the unusual DNA concentration-dependent gold nanorod aggregation. This assay method can adjust the dynamic range by controlling the concentration of nanoparticles in solution. PMID- 26282436 TI - Ethical considerations in tissue engineering research: Case studies in translation. AB - Tissue engineering research is a complex process that requires investigators to focus on the relationship between their research and anticipated gains in both knowledge and treatment improvements. The ethical considerations arising from tissue engineering research are similarly complex when addressing the translational progression from bench to bedside, and investigators in the field of tissue engineering act as moral agents at each step of their research along the translational pathway, from early benchwork and preclinical studies to clinical research. This review highlights the ethical considerations and challenges at each stage of research, by comparing issues surrounding two translational tissue engineering technologies: the bioartificial pancreas and a tissue engineered skeletal muscle construct. We present relevant ethical issues and questions to consider at each step along the translational pathway, from the basic science bench to preclinical research to first-in-human clinical trials. Topics at the bench level include maintaining data integrity, appropriate reporting and dissemination of results, and ensuring that studies are designed to yield results suitable for advancing research. Topics in preclinical research include the principle of "modest translational distance" and appropriate animal models. Topics in clinical research include key issues that arise in early-stage clinical trials, including selection of patient-subjects, disclosure of uncertainty, and defining success. The comparison of these two technologies and their ethical issues brings to light many challenges for translational tissue engineering research and provides guidance for investigators engaged in development of any tissue engineering technology. PMID- 26282437 TI - Nitrifying bacterial biomass and nitrification activity evaluated by FISH and an automatic on-line instrument at full-scale Fusina (Venice, Italy) WWTP. AB - In this study, monthly variations in biomass of ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) were analysed over a 1-year period by fluorescence in situ hybridization (FISH) at the full-scale Fusina WWTP. The nitrification capacity of the plant was also monitored using periodic respirometric batch tests and by an automated on-line titrimetric instrument (TITrimetric Automated ANalyser). The percentage of nitrifying bacteria in the plant was the highest in summer and was in the range of 10-15 % of the active biomass. The maximum nitrosation rate varied in the range 2.0-4.0 mg NH4 g(-1) VSS h(-1) (0.048-0.096 kg TKN kg(-1) VSS day(-1)): values obtained by laboratory measurements and the on-line instrument were similar and significantly correlated. The activity measurements provided a valuable tool for estimating the maximum total Kjeldahl nitrogen (TKN) loading possible at the plant and provided an early warning of whether the TKN was approaching its limiting value. The FISH analysis permitted determination of the nitrifying biomass present. The main operational parameter affecting both the population dynamics and the maximum nitrosation activity was mixed liquor volatile suspended solids (MLVSS) concentration and was negatively correlated with ammonia-oxidizing bacteria (AOB) (p = 0.029) and (NOB) (p = 0.01) abundances and positively correlated with maximum nitrosation rates (p = 0.035). Increases in concentrations led to decreases in nitrifying bacteria abundance, but their nitrosation activity was higher. These results demonstrate the importance of MLVSS concentration as key factor in the development and activity of nitrifying communities in wastewater treatment plants (WWTPs). Operational data on VSS and sludge volume index (SVI) values are also presented on 11-year basis observations. PMID- 26282438 TI - Assessing metal transfer to vegetation and grazers on reclaimed pyritic Zn and Pb tailings. AB - A study of the concentrations of zinc and lead in an engineered soil capping system overlying sulphide mine tailings was undertaken. Tailings geochemistry, soil cover and vegetation were monitored over a 4-year period, and a cattle grazing demonstration exercise was conducted over a 1-year period. Whilst the tailings had a relatively high pyrite content and demonstrated oxidation, a circum neutral pH was observed for the duration of the study period due to the high dolomitic content. No evidence of metal mobility into the soil cover and vegetation was observed over the monitoring period. Relatively high Zn herbage content is attributed to the glacial till component of the soil cover. Similarly, no evidence of metal transfer to grazing cattle was observed through blood and tissue analysis with Zn content not significantly different from control animals. Pb tissue content was below limit of detection. PMID- 26282440 TI - The sources of streamwater to small mountainous rivers in Taiwan during typhoon and non-typhoon seasons. AB - The dynamics and behaviors of streamwater chemistry are rarely documented for subtropical small mountainous rivers. A 1-year detailed time series of streamwater chemistry, using non-typhoon and typhoon samples, was monitored in two watersheds, with and without cultivation, in central Taiwan. Rainwater, soil leachate, and well water were supplemented to explain the streamwater chemistry. The concentrations of fluoride, chloride, sulfate, magnesium, potassium, calcium, strontium, silicon, and barium of all the water samples were measured. Principal component analysis and residual analysis were applied to examine the mechanisms of solute transport and investigate possible sources contributing to the streamwater chemistry. In addition to the influence of well water and soil leachate on streamwater chemistry during non-typhoon period, overland flow and surface erosion affect streamwater chemistry during the typhoon period. The latter has not been discussed in previous studies. Surface erosion is likely to be an end member and non-conservatively mixed with other end members, resulting in a previously unobserved blank zone in the mixing space. This has a particularly great impact on small mountainous watersheds, which suffer from rapid erosion. Moreover, fertilizer contaminates agricultural soil, making soil water end members more identifiable. To our knowledge, this study is the first to clearly illustrate the dynamics and sources of streamwater chemistry of small mountainous rivers that are analogous to rivers in Oceania. PMID- 26282439 TI - Polychlorinated dibenzo-p-dioxins, dibenzofurans, and dioxin-like polychlorinated biphenyls in sediments from the Yellow and Yangtze Rivers, China. AB - Polychlorinated dibenzodioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) are toxic environmental pollutants that are often found in sediments. The Yangtze and Yellow rivers in China are two of the largest rivers in Asia and are therefore important aquatic ecosystems; however, few studies have investigated the PCDD/F and PCB content in the sediments of these rivers. Accordingly, this study was conducted to generate baseline data for future environmental risk assessments. In the present study, 26 surface sediments from the middle reaches of the Yellow and Yangtze rivers were analyzed for PCDD/Fs and dioxin-like (dl) PCBs by high-resolution gas chromatography and high-resolution mass spectrometry. The ranges of PCDD/F, dl-PCB, and WHO-TEQ content in sediments from the Yellow River were 2.1-19.8, 1.11-9.9, and 0.08-0.57 pg/g (dry weight), respectively. The ranges of PCDD/F, dl-PCB, and WHO-TEQ content in sediments from the Yangtze River were 6.1-84.9, 1.8-24.1, and 0.13-0.29 pg/g (dry weight), respectively. Total organic carbon and dl-PCB contents in the Yellow River were significantly correlated (Spearman's correlation coefficient, r = 0.64, P < 0.05). It is well known that total organic carbon plays a role in the transport and redistribution of dl-PCB. Principal component analysis indicated that PCDD/Fs may arise from pentachlorophenol, sodium pentachlorophenate, and atmospheric deposition, while dl-PCBs likely originate from burning of coal and wood for domestic heating. The dioxin levels in the river sediments examined in this study were relatively low. These findings advance our knowledge regarding eco-toxicity and provide useful information regarding contamination sources. PMID- 26282441 TI - Causal nexus between energy consumption and carbon dioxide emission for Malaysia using maximum entropy bootstrap approach. AB - This study investigates the relationship between energy consumption and carbon dioxide emission in the causal framework, as the direction of causality remains has a significant policy implication for developed and developing countries. The study employed maximum entropy bootstrap (Meboot) approach to examine the causal nexus between energy consumption and carbon dioxide emission using bivariate as well as multivariate framework for Malaysia, over a period of 1975-2013. This is a unified approach without requiring the use of conventional techniques based on asymptotical theory such as testing for possible unit root and cointegration. In addition, it can be applied in the presence of non-stationary of any type including structural breaks without any type of data transformation to achieve stationary. Thus, it provides more reliable and robust inferences which are insensitive to time span as well as lag length used. The empirical results show that there is a unidirectional causality running from energy consumption to carbon emission both in the bivariate model and multivariate framework, while controlling for broad money supply and population density. The results indicate that Malaysia is an energy-dependent country and hence energy is stimulus to carbon emissions. PMID- 26282442 TI - Cancer risk of petrochemical workers exposed to airborne PAHs in industrial Lanzhou City, China. AB - This paper reports the connections between red blood cells abnormality risk of petrochemical workers and their exposure to airborne polycyclic aromatic hydrocarbons (PAHs). Urinary 1-hydroxypyrene (1-OHP), as the biomarker of PAHs exposure, was adopted to assess the exposure risk of the petrochemical workers to PAHs in Xigu, the west suburb of Lanzhou where petrochemical industries are located. Fifty-three workers, sub-grouped to 36 petrochemical workers and 17 office workers, participated in this investigation. Logistic regression model and spearman correlation analysis were performed to estimate the associations between PAHs exposure levels and red blood cells abnormality risk of petrochemical workers. Strong associations between some red cell indices (MCH, MCHC, RDW) and 1 OHP concentration were found. Results also show that the red blood cells abnormality risk increased with increasing PAHs exposure level. Compared with office workers, risk level of red blood cells abnormality in petrochemical workers was higher by 41.7 % (OR, 1.417; 95 % CI: 0.368-5.456) than that in office workers. This result was verified by the tissue-to-human blood partition coefficient for pyrene and 1-OHP. The quantitative assessments of the potential health risk through inhalation exposure to PAHs were conducted using the Incremental Lifetime Cancer Risk (ILCR) model. It was found the ILCR from inhalation exposure to PAHs for the petrochemical workers ranged from 10(-5) to 10(-4) with 95 % probability, indicating that petrochemical plant workers were under a high potential cancer risk level. PMID- 26282443 TI - Evaluation of organic amendment on the effect of cadmium bioavailability in contaminated soils using the DGT technique and traditional methods. AB - Organic amendments have been widely proposed as a remediation technology for metal-contaminated soils, but there exist controversial results on their effectiveness. In this study, the effect of pig manure addition on cadmium (Cd) bioavailability in Cd-contaminated soils was systematically evaluated by one dynamic, in situ technique of diffusive gradients in thin films (DGT) and four traditional methods based on the equilibrium theory (soil solution concentration and the three commonly used extractants, i.e., acetic acid (HAc), ethylenediamine tetraacetic acid (EDTA), and calcium chloride (CaCl2). Wheat and maize were selected for measurement of plant Cd uptake. The results showed that pig manure addition could promote the growth of two plants, accompanied by increasing biomasses of shoots and roots with increasing doses of pig manure addition. Correspondingly, increasing additions of pig manure reduced plant Cd uptake and accumulation, as indicated by the decreases of Cd concentrations in shoots and roots. The bioavailable concentrations of Cd in Cd-contaminated soils reflected by the DGT technique obviously decreased with increasing doses of pig manure addition, following the same changing trend as plant Cd uptake. Changes in soil solution Cd concentration and extractable Cd by HAc, EDTA, and CaCl2 in soils were similar to DGT measurement. Meanwhile, the capability of Cd resupply from solid phase to soil solution decreased with increasing additions of pig manure, as reflected by the decreases in the ratio (R) value of C DGT to C sol. Positive correlations were observed between various bioavailable indicators of Cd in soils and Cd concentrations in the tissues of the two plants. These findings provide stronger evidence that pig manure amendment is effective in reducing Cd mobility and bioavailability in soils and it is an ideal organic material for remediation of Cd-contaminated soils. PMID- 26282444 TI - Relationship between metabolism and ovarian activity in dairy cows with different dry period lengths. AB - The objectives of the present study were to evaluate the effects of dry period length on ovarian activity in cows fed a lipogenic or a glucogenic diet within 100 days in milk (DIM) and to determine relationships between ovarian activity and energy balance and metabolic status in early lactation. Holstein-Friesian dairy cows (n = 167) were randomly assigned to one of three dry period lengths (0, 30, or 60 days) and one of two diets in early lactation (glucogenic or lipogenic diet) resulting in a 3 * 2 factorial design. Cows were monitored for body condition score, milk yield, dry matter intake, and energy balance from calving to week 8 postpartum, and blood was sampled weekly from 95 cows from calving to week 8 postpartum. Milk samples were collected three times a week until 100 DIM postpartum for determination of progesterone concentration. At least two succeeding milk samples with progesterone concentration of 2 ng/mL or greater were used to indicate the occurrence of luteal activity. Normal resumption of ovarian cyclicity was defined as the onset of luteal activity (OLA) occurring at 45 DIM or less, followed by regular ovarian cycles of 18 to 24 days in length. Within 100 DIM postpartum, cows with a 0-day dry period had greater incidence of normal resumption of ovarian cyclicity (53.2%; 25 out of 47 cows) compared with cows with a 60-day dry period (26.0%; 13 out of 50 cows, P = 0.02). Independent of dry period length or diet, cows with OLA at less than 21 DIM had a greater body condition score during weeks 1 and 2 (P = 0.01) and weeks 1 through 8 (P = 0.01) postpartum compared with cows with OLA at greater than 30 DIM. Cows with the first ovarian cycle of medium length (18-24 days) had greater energy balance (P = 0.03), plasma concentrations of insulin (P = 0.03), glucose (P = 0.04), and insulin-like growth factor I (P = 0.04) than cows with long ovarian cycle lengths (>24 days) but had lower plasma beta-hydroxybutyrate (P < 0.01) and liver triacylglycerol (P = 0.02) concentrations than cows with short ovarian cycle lengths (<18 days) during weeks 1 through 8 postpartum. Diet did not affect the measured ovarian activity variables within 100 DIM. In conclusion, omitting the dry period (0 days) increased the incidence of normal resumption of ovarian cyclicity in dairy cows within 100 DIM compared with a conventional dry period (60 days). Short (<18 days) or long (>24 days) ovarian cycles during the first ovarian cycle postpartum were associated with severe negative energy balance and poor metabolic status in early lactation. PMID- 26282445 TI - The bilingual advantage: Elusive but worth the effort? PMID- 26282446 TI - Autism spectrum disorder: Presentation and prevalence in a nationally representative Australian sample. AB - OBJECTIVE: The aim of this study was to identify the prevalence of parent reported autism spectrum disorder diagnosis in Australia, and examine the developmental profile of children with autism spectrum disorder compared to their peers. DESIGN/SETTING: Secondary analyses were undertaken on data from the Longitudinal Study of Australian Children. PARTICIPANTS: Children were recruited at kindergarten (K cohort) and birth (B cohort), and subsequently completed two yearly 'waves' of assessments. MAIN OUTCOMES: Autism spectrum disorder diagnostic status was ascertained at Wave 4 along with age of diagnosis by parent report. Standardised tools were used to assess children's quality of life, behaviour, receptive vocabulary and non-verbal intelligence. RESULTS: Prevalence of autism spectrum disorder was 2.5% (95% confidence interval = [2.0, 3.0]) in the B cohort compared to 1.5% (95% confidence interval = [1.2, 2.0]) in the K cohort. In both cohorts, children with autism spectrum disorder had poorer mean quality of life, emotional-behavioural functioning and receptive vocabulary compared with non autism spectrum disorder peers, and a higher proportion of children with autism spectrum disorder had problems in these areas. However, between 6% and 9% of children with moderate to severe autism spectrum disorder and 12-20% with mild autism spectrum disorder were not reported to have problems with social interaction. CONCLUSION: The prevalence of a parent-reported diagnosis of autism spectrum disorder before age 7 in Australia was higher in the B cohort. Data from future Longitudinal Study of Australian Children waves will clarify whether autism spectrum disorder has been diagnosed earlier in the B cohort or if there is a continued increase in prevalence. Future waves will also provide crucial information about the types and severity of problems experienced during the primary and secondary school years which will assist service planning. PMID- 26282447 TI - Tissue-Based Proteogenomics Reveals that Human Testis Endows Plentiful Missing Proteins. AB - Investigations of missing proteins (MPs) are being endorsed by many bioanalytical strategies. We proposed that proteogenomics of testis tissue was a feasible approach to identify more MPs because testis tissues have higher gene expression levels. Here we combined proteomics and transcriptomics to survey gene expression in human testis tissues from three post-mortem individuals. Proteins were extracted and separated with glycine- and tricine-SDS-PAGE. A total of 9597 protein groups were identified; of these, 166 protein groups were listed as MPs, including 138 groups (83.1%) with transcriptional evidence. A total of 2948 proteins are designated as MPs, and 5.6% of these were identified in this study. The high incidence of MPs in testis tissue indicates that this is a rich resource for MPs. Functional category analysis revealed that the biological processes that testis MPs are mainly involved in are sexual reproduction and spermatogenesis. Some of the MPs are potentially involved in tumorgenesis in other tissues. Therefore, this proteogenomics analysis of individual testis tissues provides convincing evidence of the discovery of MPs. All mass spectrometry data from this study have been deposited in the ProteomeXchange (data set identifier PXD002179). PMID- 26282449 TI - Multiple visions of Indonesia's mud volcano: understanding representations of disaster across discursive settings. AB - The Lapindo mudflow is one of the most controversial disasters in Indonesian history. Despite its unique biophysical features, most consider the mudflow a social disaster as scientific conflicts about its main trigger have evolved into legal disputes over accountability and rights. This paper examines this 'trigger debate', the stakes of scientific contention and the broader social and natural dynamics that shape the terms of this debate. A Latourian impulse drives this analysis, which aims to improve both understandings of--and responses to--complex disasters. This paper also notes that the stakes of representation extend to constructions of its stakeholders, especially to victims. As socionatural disasters become an increasingly common feature of the contemporary world, from mud volcanoes to extreme weather events caused by global warming, it is more important than ever to understand the dynamics of representing disasters and stakeholders. PMID- 26282448 TI - Financial burden among US households affected by cancer at the end of life. AB - OBJECTIVE: Economic burden on families coping with end-stage cancer remains poorly understood. Advanced malignancy threatens financial stability of families, and interventions are needed to buffer them from impoverishment. This study examined the relationship between subjective and objective assessments of financial burden on families (financial strain and stress, respectively) and identified potentially modifiable factors to inform intervention efforts. METHODS: Using national survey data, we analyzed responses from households that had recently experienced a cancer death; 176 of households provided information on financial strain, and 158 provided data on financial stress. In addition to self-reported appraisals of financial burden, measures assessed elements of the cancer care experience, treatment, symptom burden, work impact, insurance coverage, and demographics. RESULTS: Despite being well insured, approximately a quarter of respondents reported that the cost of care was a major financial burden, and a third used all or most of their savings. Financial strain and stress were moderately positively correlated (r = 0.46, p < 0.01). Higher financial stress scores were negatively correlated with decedent's age at death (r = -0.34, p < 0.01), and minority respondents ('other' race) reported much higher financial stress (M = 4.7; SD = 3.2) than White (M = 0.8; SD = 1.4) or Black (M = 1.6; SD = 2.2) respondents (p < 0.001). Financial burden was also associated with no or limited insurance coverage, changes in employment, severe pain and nausea, and provider interactions during the cancer care experience (e.g., whether the MD paid attention to non-medical factors or having unanswered questions about medications) (p < 0.05 for all). CONCLUSIONS: The cancer care experience, symptoms, and work impact were associated with financial burden and have important implications for research and practice. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26282450 TI - The HLA-A*2402/Cw*0102 haplotype is associated with lamotrigine-induced maculopapular eruption in the Korean population. AB - The use of lamotrigine (LTG) can be limited by the occurrence of cutaneous adverse drug reactions (cADRs) that range from maculopapular eruption (MPE) to the more severe Stevens-Johnson syndrome and toxic epidermal necrolysis. A few human leukocyte antigen (HLA)-related genetic risk factors for carbamazepine induced cADR have been identified. However, the HLA-related genetic risk factors associated with LTG-induced cADR are not yet well known. We performed HLA genotyping in 50 Korean patients with epilepsy, including 21 patients presenting LTG-induced MPE and 29 LTG-tolerant patients. A significant association between the HLA-A*2402 allele and LTG-induced MPE was identified, in comparison with the LTG-tolerant group (odds ratio [OR] 4.09, p = 0.025) and the general Korean population (OR 3.949, p = 0.005). The frequencies of the Cw*0102 or Cw*0702 alleles were significantly higher in the LTG-MPE group than in the Korean population, whereas the frequency of the A*3303 allele was lower. The coexistence of the A*2402 and Cw*0102 alleles was significantly associated with the LTG-MPE group when compared to the LTG-tolerant group (OR 7.88, p = 0.007). In addition, the Cw*0701 allele was more frequent in the LTG-tolerant group than in the Korean population. These findings suggest the presence of HLA-related genetic risk factors for LTG-induced MPE in the Korean population. PMID- 26282451 TI - Synthesis, Single Crystal, and Physical Properties of Asymmetrical Thiophene/Selenophene-Fused Twistacenes. AB - Two asymmetrical twistacenes, PyPT and PyPS, have been synthesized and characterized. Single crystal X-ray analyses show that both of them have twisted structures with a torsion angle of 26.65 degrees for PyPT and 26.59 degrees for PyPS measured between plane C5-C23-C25 and plane C13-C15-C26. The thiophene/selenophene-fused acenes emit blue fluorescence with quantum yields of 0.39 for PyPT and 0.04 for PyPS in organic solvents, whereas the all-carbon molecule HBP emits green fluorescence. Meanwhile, PyPT and PyPS show a similar reversible oxide procedure with the onset potentials of 0.73 and 0.72 V, respectively. In addition, PyPT and PyPS can self-assemble to form nanoparticles in a mixture of THF/H2O through re-precipitation method. PMID- 26282452 TI - Carbon monoxide and stroke: A time series study of ambient air pollution and emergency hospitalizations. AB - BACKGROUND: Recent experimental and clinical studies suggested that exogenous carbon monoxide (CO) at low concentrations may have beneficial neuroprotective effects under certain circumstances. However, population-based epidemiological studies of environmentally relevant CO exposure generated mixed findings. The present study aimed to examine the short-term association of ambient CO with emergency stroke hospitalizations. METHODS: A time series study was conducted. Daily air pollution concentrations and emergency hospital admission data from January 2004 to December 2011 in Hong Kong were collected. Generalized additive Poisson models were used to estimate the associations between daily 24-hour mean concentrations of CO and emergency hospital admissions for stroke, while controlling for other traffic related co-pollutants: NO2 and PM2.5. Sensitivity analyses were performed using daily 1-hour maximum concentration of CO as exposure indicator. RESULTS: Negative associations were observed between ambient CO concentrations and emergency hospital admissions for stroke. The previous 1-3 day cumulative exposure to CO was associated with a -2.0% (95%CI, -3.3% to -0.7%) decrease in stroke admissions per interquartile range (IQR) increment in CO concentration (0.3 ppm). Similar results were obtained when using 1-hour maximum concentration of CO as exposure indicator. The negative association was robust to the co-pollutant adjustment for either NO2 or PM2.5. Females and elders appeared to be more sensitive to ambient CO exposure. The negative association tended to be larger in cool season. CONCLUSION: Short-term exposure to ambient CO was associated with decreased risk of emergency hospitalizations for stroke, suggesting some acute protective effects of CO exposure against stroke onsets. PMID- 26282454 TI - PREVENTING CHILD AND ADOLESCENT ANXIETY DISORDERS: OVERVIEW OF SYSTEMATIC REVIEWS. AB - Overviews of systematic reviews (OSRs) provide rapid access to high quality, consolidated research evidence about prevention intervention options, supporting evidence-informed decision-making, and the identification of fruitful areas of new research. This OSR addressed three questions about prevention strategies for child and adolescent anxiety: (1) Does the intervention prevent anxiety diagnosis and/or reduce anxiety symptoms compared to passive controls? (2) Is the intervention equal to or more effective than active controls? (3) What is the evidence quality (EQ) for the intervention? Prespecified inclusion criteria identified systematic reviews and meta-analyses (2000-2014) with an AMSTAR quality score >= 3/5. EQ was rated using Oxford evidence levels EQ1 (highest) to EQ5 (lowest). Three reviews met inclusion criteria. One narrative systematic review concluded school-based interventions reduce anxiety symptoms. One meta analysis pooled 65 randomized controlled trials (RCTs; any intervention) and reported a small, statistically significant reduction in anxiety symptoms and diagnosis incidence. Neither review provided pooled effect size estimates for specific intervention options defined by type (i.e., universal/selective/indicated), intervention content, or comparison group (i.e., passive/active control), thus precluding EQ ratings. One meta-analysis pooled trials of vigorous exercise and reported small, nonstatistically significant reductions in anxiety symptoms for comparisons against passive and active controls (EQ1). Better use of primary studies in meta-analyses, including program specific pooled effect size estimates and network meta-analysis is needed to guide evidence-informed anxiety prevention program choices. RCTs of innovative community/primary care based interventions and web-based strategies can fill knowledge gaps. PMID- 26282455 TI - Undiagnosed cardiac sarcoidosis presenting as complete heart block and ventricular arrhythmia. AB - Cardiac involvement in sarcoidosis has been reported to be as high as 50% of cases and it is well documented that it is associated with a poorer prognosis. Early recognition and treatment is key to reducing the risk of fatal arrhythmias and heart failure. We report a case of undiagnosed systemic sarcoidosis in a young man who initially presented to the emergency department with complete heart block in the context of preserved biventricular systolic function, and then again with ventricular tachycardia and moderately impaired left ventricular systolic function. We discuss how 18F-fluorodeoxyglucose positron emission tomography with CT was used for accurate diagnosis and how its role in the management of sarcoidosis has expanded with recent evidence suggesting it to be a mainstay of management and disease monitoring in cardiac sarcoidosis. PMID- 26282453 TI - Association studies of genomic variants with treatment response to risperidone, clozapine, quetiapine and chlorpromazine in the Chinese Han population. AB - Schizophrenia is a widespread mental disease with a prevalence of about 1% in the world population. Continuous long-term treatment is required to maintain social functioning and prevent symptom relapse of schizophrenia patients. However, there are considerable individual differences in response to the antipsychotic drugs. There is a pressing need to identify more drug-response-related markers. But most pharmacogenomics of schizophrenia have typically focused on a few candidate genes in small sample size. In this study, 995 subjects were selected for discovering the drug-response-related markers. A total of 77 single-nucleotide polymorphisms of 25 genes have been investigated for four commonly used antipsychotic drugs in China: risperidone, clozapine, quetiapine, and chlorpromazine. Significant associations with treatment response for several genes, such as CYP2D6, CYP2C19, COMT, ABCB1, DRD3 and HTR2C have been verified in our study. Also, we found several new candidate genes (TNIK, RELN, NOTCH4 and SLC6A2) and combinations (haplotype rs1544325-rs5993883-rs6269-rs4818 in COMT) that are associated with treatment response to the four drugs. Also, multivariate interactions analysis demonstrated the combination of rs6269 in COMT and rs3813929 in HTR2C may work as a predictor to improve the clinical antipsychotic response. So our study is of great significance to improve current knowledge on the pharmacogenomics of schizophrenia, thus promoting the implementation of personalized medicine in schizophrenia.The Pharmacogenomics Journal advance online publication, 18 August 2015; doi:10.1038/tpj.2015.61. PMID- 26282456 TI - Isolated CNS Whipple's disease: a diagnostic dilemma. PMID- 26282457 TI - A rare case of bilateral chylothorax: a diagnostic challenge--follicular lymphoma versus primary effusion lymphoma. AB - Chylothorax is most common on the left side owing to the position of the thoracic duct. Malignancy-associated chylothorax is not uncommon. However, bilateral chylothorax is rare and malignancy should be a consideration in absence of trauma. We report a case of a patient with follicular lymphoma who presented with bilateral pleural effusion; pleural fluid analysis confirmed chylothorax. The patient did not have any significant peripheral or axial lymphadenopathy, which made the diagnosis difficult in absence of histopathology. Pleural fluid analysis was negative for malignant cells, however, the flow cytometry markers were suggestive of follicular lymphoma. Primary effusion lymphoma, which could have been another possibility, was ruled out by the flow cytometry markers. We conclude that pleural fluid flow cytometry markers play an important role where there is no significant lymphadenopathy and in absence of histopathological diagnosis. This demands further evaluation. PMID- 26282458 TI - Transplantation of placenta-derived mesenchymal stem cells enhances angiogenesis after ischemic limb injury in mice. AB - Mesenchymal stem cell-based therapy has emerged as a promising approach for the treatment of peripheral arterial disease. The purpose of this study was to examine the potential effects of human placenta-derived mesenchymal stem cells (PMSCs) on mouse hindlimb ischemia. PMSCs were isolated from human placenta tissue and characterized by flow cytometry. An in vivo surgical ligation-induced murine limb ischemia model was generated with fluorescent dye (CM-DiI) labelled PMSCs delivered via intramuscular injection. Our data show that PMSCs treatment significantly enhanced microvessel density, improved blood perfusion and diminished pathologies in ischemic mouse hindlimbs as compared to those in the control group. Further immunostaining studies suggested that injected PMSCs can incorporate into the vasculature and differentiate into endothelial and smooth muscle cells to enhance angiogenesis in ischemic hind limbs. This may in part explain the beneficial effects of PMSCs treatment. Taken together, we found that PMSCs treatment might be an effective treatment modality for treatment of ischemia-induced injury to mouse hind limbs by enhancement of angiogenesis. PMID- 26282460 TI - Quick Fabrication of Large-area Organic Semiconductor Single Crystal Arrays with a Rapid Annealing Self-Solution-Shearing Method. AB - In this paper, we developed a new method to produce large-area single crystal arrays by using the organic semiconductor 9, 10-bis (phenylethynyl) anthracene (BPEA). This method involves an easy operation, is efficient, meets the demands of being low-cost and is independent of the substrate for large-area arrays fabrication. Based on these single crystal arrays, the organic field effect transistors exhibit the superior performance with the average mobility extracting from the saturation region of 0.2 cm(2) V(-1)s(-1) (the highest 0.47 cm(2) V( 1)s(-1)) and on/off ratio exceeding 10(5). In addition, our single crystal arrays also show a very high photoswitch performance with an on/off current ratio up to 4.1 * 10(5), which is one of the highest values reported for organic materials. It is believed that this method provides a new way to fabricate single crystal arrays and has the potential for application to large area organic electronics. PMID- 26282459 TI - Dual action of leptin on rest-firing and stimulated catecholamine release via phosphoinositide 3-kinase-driven BK channel up-regulation in mouse chromaffin cells. AB - KEY POINTS: Leptin is an adipokine produced by the adipose tissue regulating body weight through its appetite-suppressing effect and, as such, exerts a relevant action on the adipo-adrenal axis. Leptin has a dual action on adrenal mouse chromaffin cells both at rest and during stimulation. At rest, the adipokine inhibits the spontaneous firing of most cells by enhancing the probability of BK channel opening through the phosphoinositide 3-kinase signalling cascade. This inhibitory effect is absent in db(-) /db(-) mice deprived of Ob receptors. During sustained stimulation, leptin preserves cell excitability by generating well adapted action potential (AP) trains of lower frequency and broader width and increases catecholamine secretion by increasing the size of the ready-releasable pool and the rate of vesicle release. In conclusion, leptin dampens AP firing at rest but preserves AP firing and enhances catecholamine release during sustained stimulation, highlighting the importance of the adipo-adrenal axis in the leptin mediated increase of sympathetic tone and catecholamine release. ABSTRACT: Leptin is an adipokine produced by the adipose tissue regulating body weight through its appetite-suppressing effect. Besides being expressed in the hypothalamus and hippocampus, leptin receptors (ObRs) are also present in chromaffin cells of the adrenal medulla. In the present study, we report the effect of leptin on mouse chromaffin cell (MCC) functionality, focusing on cell excitability and catecholamine secretion. Acute application of leptin (1 nm) on spontaneously firing MCCs caused a slowly developing membrane hyperpolarization followed by complete blockade of action potential (AP) firing. This inhibitory effect at rest was abolished by the BK channel blocker paxilline (1 MUm), suggesting the involvement of BK potassium channels. Single-channel recordings in 'perforated microvesicles' confirmed that leptin increased BK channel open probability without altering its unitary conductance. BK channel up-regulation was associated with the phosphoinositide 3-kinase (PI3K) signalling cascade because the PI3K specific inhibitor wortmannin (100 nm) fully prevented BK current increase. We also tested the effect of leptin on evoked AP firing and Ca(2+) -driven exocytosis. Although leptin preserves well-adapted AP trains of lower frequency, APs are broader and depolarization-evoked exocytosis is increased as a result of the larger size of the ready-releasable pool and higher frequency of vesicle release. The kinetics and quantal size of single secretory events remained unaltered. Leptin had no effect on firing and secretion in db(-) /db(-) mice lacking the ObR gene, confirming its specificity. In conclusion, leptin exhibits a dual action on MCC activity. It dampens AP firing at rest but preserves AP firing and increases catecholamine secretion during sustained stimulation, highlighting the importance of the adipo-adrenal axis in the leptin-mediated increase of sympathetic tone and catecholamine release. PMID- 26282461 TI - Effects of glucose-lowering and multifactorial interventions on cardiovascular and mortality outcomes: a meta-analysis of randomized control trials. AB - INTRODUCTION: The effect of intensive glycaemic control alone or as part of a multifactorial intervention on cardiovascular and mortality outcomes is not fully understood. In addition, the interaction of duration of diabetes diagnosis on cardiovascular and mortality outcomes is unclear. AIM: To quantify the effect of intensive treatment (i.e. intensive glucose lowering either alone or as part of a multifactorial intervention) on non-fatal myocardial infarction (MI), non-fatal stroke, cardiovascular disease (CV) mortality and all-cause mortality in patients with Type 2 diabetes. A secondary objective was to investigate the association between the treatment effect and trial-level characteristics such as average age, duration of Type 2 diabetes, the percentage male and the baseline event rate. METHODS: We searched MEDLINE, Embase and the Cochrane Central Register of Controlled Trials without language restrictions from inception to 13 May 2015. We included randomized controlled trials (RCTs) that evaluated intensive treatment in adult patients with Type 2 diabetes. The review was registered on PROSPERO (registration number 42014013860). We pooled rates across studies using random effects meta-analysis and investigated study-level covariate associations using Bayesian meta-regression. RESULTS: A total of 19 RCTs were included: 16 examined non-fatal MI (n = 79 595), 14 non-fatal stroke (n = 78 568), 18 cardiovascular mortality (n = 83 938) and 18 all-cause mortality (n = 84 266). There was evidence to suggest that compared with standard care, intensive treatment reduced the risk of non-fatal MI [risk ratio (RR) 0.90, 95% confidence interval (CI) 0.83 0.96], but not non-fatal stroke (RR 0.96, 95% CI 0.86-1.07), CV mortality (RR 1.00, 95% CI 0.90-1.11) or all-cause mortality (RR 1.00, 95% CI 0.94-1.06). Compared with standard care, multifactorial interventions alone reduced non-fatal stroke (RR 0.53, 95% CI 0.32-0.0.87) but not non-fatal MI (RR 0.66, 95% CI 0.38 1.03), CV mortality (RR 0.72, 95% CI 0.46-1.14) or all-cause mortality (RR 0.82, 95% CI 0.64-1.05). There was no evidence to suggest that the effect of intensive treatment on cardiovascular and mortality outcomes was associated with mean age, mean duration of Type 2 diabetes and percentage of male patients across trials. There was evidence to suggest that the effectiveness of intensive treatment to reduce mortality outcomes increases as the baseline incidence of cardiovascular mortality [ratio of hazard = 0.82, 95% credible interval (CrI) 0.65-0.99] increased across trials, but not baseline incidence of non-fatal MI, non-fatal stroke and all-cause mortality. Intensive glucose-lowering and multifactorial interventions are predicted to have the desired beneficial effect of reducing CVD mortality in populations where the incidence rate is greater than about 6.3 CVD deaths per 1000 person-years or an average 10-year CVD risk of 6.3%. CONCLUSIONS: Apart from non-fatal MIs, there was no evidence that intensive glucose-lowering and multifactorial interventions reduced or increased the risk of cardiovascular and mortality outcomes. Intensive glucose-lowering and multifactorial interventions are likely to be beneficial in populations with a higher baseline incidence of CV mortality, but there was no evidence of an association with the mean duration of Type 2 diabetes. Multifactorial interventions had a much greater impact on non-fatal MI and non-fatal strokes. (PROSPERO registration no.: 42014013860). PMID- 26282462 TI - Skin perfusion responses under normal and combined loadings: Comparisons between legs with venous stasis ulcers and healthy legs. AB - BACKGROUND: Venous ulcers, also known as stasis ulcers, are skin wounds often found at the medial surface of the lower leg. These wounds are related to chronic venous insufficiencies and affect almost 2.5 million patients every year in the United States. METHOD: Eighteen participants with venous stasis ulcers on at least one leg and twenty healthy participants were tested. Normal and combined normal and shear loadings were applied to each lower leg and local blood perfusion was monitored. Basal perfusion, post-occlusive reactive hyperemia as well as changes in perfusion due to different loadings were compared. FINDINGS: Legs with existing venous stasis ulcers ("wounded legs") had the highest reactive hyperemia and basal perfusion values. Legs without ulcers but from participants with venous stasis ulcers ("non-wounded legs") had intermediate reactive hyperemia, and healthy legs exhibited the lowest values. Wounded legs also exhibited the largest decrease in blood perfusion under both normal and combined loadings. Non-wounded legs decreased perfusion similarly to healthy legs under normal loadings; however, non-wounded legs exhibited larger decreases in blood flow than healthy legs in response to shear and normal loading together. INTERPRETATION: These results suggest that patients with venous stasis disease have abnormal responses to tissue loading and raise the possibility that this technique may have the potential to identify patients at risk for developing a venous stasis ulcer. Moreover, they emphasize the importance of studying shear loading in addition to normal loading in attempting to understand the pathophysiology of this disease. PMID- 26282463 TI - Bone stress in runners with tibial stress fracture. AB - BACKGROUND: Combinations of smaller bone geometry and greater applied loads may contribute to tibial stress fracture. We examined tibial bone stress, accounting for geometry and applied loads, in runners with stress fracture. METHODS: 23 runners with a history of tibial stress fracture & 23 matched controls ran over a force platform while 3-D kinematic and kinetic data were collected. An elliptical model of the distal 1/3 tibia cross section was used to estimate stress at 4 locations (anterior, posterior, medial and lateral). Inner and outer radii for the model were obtained from 2 planar x-ray images. Bone stress differences were assessed using two-factor ANOVA (alpha=0.05). Key contributors to observed stress differences between groups were examined using stepwise regression. FINDINGS: Runners with tibial stress fracture experienced greater anterior tension and posterior compression at the distal tibia. Location, but not group, differences in shear stress were observed. Stepwise regression revealed that anterior posterior outer diameter of the tibia and the sagittal plane bending moment explained >80% of the variance in anterior and posterior bone stress. INTERPRETATION: Runners with tibial stress fracture displayed greater stress anteriorly and posteriorly at the distal tibia. Elevated tibial stress was associated with smaller bone geometry and greater bending moments about the medial-lateral axis of the tibia. Future research needs to identify key running mechanics associated with the sagittal plane bending moment at the distal tibia as well as to identify ways to improve bone geometry in runners in order to better guide preventative and rehabilitative efforts. PMID- 26282464 TI - Recent Patents on Nanoparticles and Nanoformulations for Cancer Therapy. AB - Cancer is a major malignancy which has claimed numerous lives worldwide. Despite huge resources being utilized to develop cancer therapeutics, no effective cure has been found so far. Hence there is a need to look at emerging technologies for a solution. Nanoparticle is one such technology that has become feasible and popular in the past few years. Though, it has not emerged as a drug delivery platform of choice for cancer therapeutics it has shown enormous promise. Different types of materials such as polymer, lipid, magnet, metal based nanoparticles have been developed to enhance the effectiveness of current treatment. This manuscript will review different aspects of nanoparticles and recent research advances and patents for treatment of cancer. PMID- 26282465 TI - Primary cutaneous follicular helper T-cell lymphoma. AB - Follicular helper T-cells (TFH) represent a specific subset of CD4-positive helper T-cells that help B-cells to differentiate into long-lived antibody secreting plasma cells or memory B-cells. The expression of TFH markers in neoplastic T-cells, traditionally related to the angioimmunoblastic (AITL) subgroup of peripheral T-cell lymphomas, is nowadays well-known to be more widespread than previously thought. We report hereby a case of cutaneous T-cell lymphoma in a 75-year-old woman, whose morphological and immunophenotypical features raises the differential diagnosis between cutaneous involvement by AITL and the recently described primary cutaneous T-cell lymphoma with follicular helper-phenotype. PMID- 26282466 TI - Treating ischaemia-reperfusion injury with prostaglandin E1 reduces the risk of early hepatocellular carcinoma recurrence following liver transplantation. AB - BACKGROUND: Surgical stress by hepatic ischaemia-reperfusion (I/R) is supposed to promote intra- and extrahepatic tumour recurrence. Treatment with prostaglandin E1 (PGE1) has been shown to attenuate hepatic I/R injury in liver transplant patients, but the potential anti-cancer effects have not been analysed. AIM: To evaluate the impact of PGE1 therapy on risk of hepatocellular carcinoma (HCC) recurrence in liver transplant patients. METHODS: A retrospective review of 106 liver transplant patients with HCC was conducted. Fifty-nine patients underwent early post-liver transplantation (LT) treatment with the stable PGE1 analogue alprostadil. Administration of alprostadil was correlated with outcome in uni- and multivariate analysis. Subgroup analysis focused on patients with HCC beyond the Milan criteria (Milan Out) on radiographic imaging. RESULTS: Three- and 5 year recurrence-free survival rates were 87.9% and 85.7% in the PGE1-group, but only 65.3% and 63.1% in the non-PGE1-population (P = 0.003). Multivariate Cox regression analysis identified absence of PGE1-treatment (HR = 11.42), along with presence of poor tumour grading (HR = 2.69) and microvascular tumour invasion (HR = 35.8) to be independently associated with early (within 12 months) HCC recurrence. In Milan Out-patients, only therapy with PGE1 (HR = 5.09) and well/moderate tumour differentiation (HR = 6.51) were independent promoters of recurrence-free survival. CONCLUSIONS: Treating hepatic ischaemia-reperfusion injury with alprostadil reduces the risk of early HCC recurrence following LT. In particular patients with HCC exceeding the Milan criteria seem to benefit from PGE1-treatment. The molecular mechanisms of the anti-tumour effects need to be further assessed. PMID- 26282468 TI - Leadless pacemakers: leading us into the future? PMID- 26282467 TI - Dysregulated cytokine expression in lesional and nonlesional skin in hidradenitis suppurativa. AB - BACKGROUND: There is a dearth of information on the precise pathogenesis of hidradenitis suppurativa (HS), but immune dysregulation is implicated. OBJECTIVES: To determine the nature of the immune response in HS. METHODS: Skin biopsies - lesional, perilesional (2 cm away) and uninvolved (10 cm away) - were obtained from patients with HS and healthy controls. The expression of various cytokines was determined by enzyme-linked immunosorbent assay, flow cytometry and real-time polymerase chain reaction. RESULTS: The expression of the inflammatory cytokines interleukin (IL)-17, IL-1beta and tumour necrosis factor-alpha was enhanced in lesional skin of patients with HS. In addition, IL17A and IL1B mRNA were enhanced in clinically normal perilesional skin. CD4(+) T cells produced IL 17 in HS, while CD11c(+) CD1a(-) CD14(+) cells were sources of IL-1beta. Activated caspase-1 was detected in HS skin and was associated with enhanced expression of NLRP3 and IL18. Inhibition of caspase-1 decreased IL-1beta and IL 18 production, suggesting that the caspase-1 pathway participates in IL-1beta and IL-18 expression in HS. Abnormal cytokine expression was detected in perilesional and uninvolved skin, which may suggest that subclinical inflammation is present in HS skin prior to the formation of an active lesion. CONCLUSIONS: This study demonstrates that CD4(+) T cells produce IL-17 in HS and that the IL-17 pathway may be important in HS pathogenesis. CD11c(+) CD1a(-) CD14(+) cells are a source of IL-1beta in HS, the production of which was shown to be mediated, in part, via a caspase-1-dependent pathway. These results suggest that IL-17 and the caspase-1 associated cytokines IL-1beta and IL-18 may play a role in the pathogenesis of HS. PMID- 26282469 TI - Ventricular arrhythmias after cardiac resynchronization therapy: does reverse remodelling reverse risk? PMID- 26282470 TI - Chronic and acute LRRK2 silencing has no long-term behavioral effects, whereas wild-type and mutant LRRK2 overexpression induce motor and cognitive deficits and altered regulation of dopamine release. AB - INTRODUCTION: Germline silencing of the PD-related protein LRRK2 does not alter glutamate or dopamine release in adult mice, but some exploratory abnormalities have been reported with ageing. Contrastingly, high levels of human LRRK2 cause locomotor alterations and cognitive deficits accompanied by reduced striatal dopamine levels, with the latter also observed in G2019S mutant mice. Comparative cognitive and motor behavioral testing of LRRK2 KO, overexpressor and mutant overexpressor mice has not previously been reported. METHODS: Parallel, comparative behavioral characterization was performed assessing motor and cognitive abilities. Striatal antisense oligonucleotide injections were conducted to investigate the effects of acute LRRK2 silencing on behavior and dopamine fiber density. Striatal synaptosomes prepared from hG2019S mice assessed vesicular release of dopamine and its sensitivity to D2 autoreceptor stimulation. RESULTS: Genetic ablation of LRRK2 has no long-term consequences on motor or cognitive function. Consistently, no effects on behavior or dopaminergic fiber density were observed following acute striatal silencing. Conversely, 12-month OE mice show persistent locomotor deficits and worsening of cognitive abilities; whereas, hG2019S mice display early hyperactivity and effective learning and memory that progress to decreased motor and cognitive deficits at older ages. The G2019S mutation does not affect vesicular dopamine release, but decreases its sensitivity to D2-mediated inhibition. CONCLUSION: LRRK2 silencing is well tolerated in mouse, arguing PD does not result from LRRK2 loss of function. High levels of WT and G2019S LRRK2 produce similar but temporally distinct phenotypes, potentially modeling different stages of disease progression. The data implicate gain of LRRK2 function in the pathogenesis of PD. PMID- 26282471 TI - Gene Expression Signatures as Biomarkers of Tumour Hypoxia. AB - Hypoxia is a feature of most solid tumours and is associated with a poor prognosis. The hypoxic environment can reduce the efficacy of radiotherapy and some chemotherapeutics, and has been investigated extensively as a therapeutic target. The clinical use of hypoxia-targeting treatment will benefit from the development of a biomarker to assess tumour hypoxia. There are several possible techniques that measure either the level of oxygen or the tumour molecular response to hypoxia. The latter includes gene expression profiling, which measures the transcriptional response of a tumour to its hypoxic microenvironment. A systematic review identified 32 published hypoxia gene expression signatures. The methods used for their derivation varied, but are broadly classified as: (i) identifying genes with significantly higher or lower expression in cancer cells cultured under hypoxic versus normoxic conditions; (ii) using either previously characterised hypoxia-regulated genes/biomarkers to define hypoxic tumours and then identifying other genes that are over- or under expressed in the hypoxic tumours. Both generated gene signatures useful in furthering our understanding of hypoxia biology. However, signatures derived using the second method seem to be superior in terms of providing prognostic information. Here we summarise all 32 published hypoxia signatures, discuss their commonalities and differences, and highlight their strengths and limitations. This review also highlights the importance of reproducibility and gene annotation, which must be accounted for to transfer signatures robustly for clinical application as biomarkers. PMID- 26282472 TI - Respiratory disease in New Zealand. PMID- 26282473 TI - Have chronic respiratory disease, will travel? PMID- 26282474 TI - How do you deal with burnout in the clinical workplace? PMID- 26282475 TI - Vitamin D supplementation in patients with COPD: Twitter discussions on behalf of the University of Toronto Respirology and Sleep Journal Club. PMID- 26282476 TI - Vitamin D supplementation in patients with COPD: Twitter discussions on behalf of the University of Toronto Respirology and Sleep Journal Club--Authors' Reply. PMID- 26282477 TI - Bronchodilator reversibility and cardiac considerations with use of tiotropium. PMID- 26282478 TI - Blood eosinophil counts as markers of response to inhaled corticosteroids in COPD? PMID- 26282479 TI - Blood eosinophil counts as markers of response to inhaled corticosteroids in COPD?--Authors' reply. PMID- 26282481 TI - Corrections. PMID- 26282480 TI - Occupational asthma from a horticultural nematode, Steinernema feltiae. PMID- 26282482 TI - Invisible suffering: breathlessness in and beyond the clinic--a reply. PMID- 26282483 TI - Shared Decision-Making in Nursing Homes: Factors Associated With the Empowerment of Direct Care Workers. AB - OBJECTIVE: The advantages of empowering direct care workers (DCWs) within nursing homes (NHs) are well documented. Our objective is to identify factors that create DCW empowerment as this has not received adequate attention. METHOD: The data come from a larger study focused on the empowerment of DCWs in NHs. A self administered instrument was completed by 372 DCWs within 11 NHs in the north Texas region. Cluster analysis and ordinary least squares (OLS) regression were performed. RESULTS: Feedback from nurse management to DCWs was positively associated with shared decision-making (SDM) and ranked highest followed by information exchange, trust in management, and wages linked to performance. DISCUSSION: SDM may be enhanced where nurse management shares relevant information with the DCWs, listens to their ideas, provides explanations when DCW suggestions are not used, and does so in a supportive environment. Organizational characteristics of importance include linking wages to DCW performance and providing an accessible training program. PMID- 26282484 TI - Distributions of selected urinary metabolites of volatile organic compounds by age, gender, race/ethnicity, and smoking status in a representative sample of U.S. adults. AB - Data from National Health and Nutrition Examination Survey for the years 2011 2012 were used to evaluate variability in the observed levels of 19 urinary metabolites of 15 parent volatile organic compounds (VOCs) by age, gender, race/ethnicity, and smoking status. Smokers were found to have statistically significantly higher adjusted levels than nonsmokers for selected urinary metabolites of acrolein, acrylamide, acrylonitrile, 1,3-butadiene, carbon disulfide, crotonaldehyde, cyanide, N,N-dimethylformamide, ethylbenzene-styrene, propylene oxide, styrene, and xylene. Female nonsmokers were found to have lower adjusted levels of selected metabolites of acrolein, carbon-disulfide, and N,N dimethylformamide than male nonsmokers but female smokers had higher levels of each of these metabolites than male smokers. In addition, female smokers also had higher adjusted levels of selected metabolites of 1,3-butadiene, crotonaldehyde, cyanide, and ethylbenzene-styrene. Thus, constituents other than VOCs in tobacco smoke affect excretion of certain VOC metabolites differently among males and females. Non-Hispanic whites (NHW) had higher adjusted levels than non-Hispanic blacks (NHB) for 8 metabolites. NHB had statistically significantly lower adjusted levels than Hispanics for 5 VOC metabolites and lower levels than non Hispanic Asians (NHAS) for 6 metabolites. Hispanics had statistically significantly higher levels than NHAS for 5 metabolites. Levels of 11 of the 19 metabolites analyzed increased with increase in age. Exposure to environmental tobacco smoke at home was associated with increased levels of 9 metabolites. Increase in the number of days tobacco products were used during the last five days was associated with increased levels of 12 of the 19 VOC metabolites. PMID- 26282485 TI - Polymorphisms in DNA repair and multidrug resistance genes among Sindhis of Central India. AB - Polymorphisms in DNA repair and multidrug resistance genes might contribute to interindividual and interethnic differences in DNA repair capacity and drug disposition respectively. In the present study, we determined the allele and genotype frequencies of four single nucleotide polymorphisms (SNPs) located in the DNA repair genes, XRCC1, XRCC3, XPD, OGG1, namely XRCC1 Arg399Gln, XRCC3 Thr241Met, XPD Lys751Gln, and OGG1 Ser326Cys, respectively and two SNPs located in the multidrug resistance gene, ABCB1, namely ABCB1 C3435T and ABCB1 C1236T, in 33-35 healthy and unrelated Sindhi individuals, residing in the Vidarbha region of Central India and compared them with the Maharashtrian population from the same geographical region and some other HapMap populations from the HapMap database. The study findings reveal that the Indian Sindhis are closely related to the Maharashtrians as well as Utah residents with Northern and Western European ancestry and Gujarati Indians in Houston, Texas in the HapMap database. PMID- 26282486 TI - Fast determination of underivatized gentamicin C components and impurities by LC MS using a porous graphitic carbon stationary phase. AB - Gentamicin C antibiotics are important because they are active against many multidrug-resistant Gram-negative bacilli. Unfortunately, their clinical usefulness is limited by their toxicity. Because of the difficulty involved in separating its different components, the US and European pharmacopeias both specify that the composition of gentamicin C should be determined by liquid chromatography with pulsed electrochemical detection. Here, we assess the usefulness of a porous graphitic carbon (PGC) HPLC column for separating the components of gentamicin C, and report chromatographic conditions that enable its direct characterization by PGC chromatography directly coupled to electrospray mass spectrometry. Native major components of gentamicin and impurities in commercial formulations were retained and separated on the PGC column without any need for derivatization, using mobile phases basified with ammonium hydroxide. When coupled with detection by conventional electrospray ion trap mass spectrometry (ESI-IT-MS), several previously reported impurities were detected easily, including the most polar gentamicin impurity, garamine. When operating in full-scan mode, it was possible to identify and quantitate gentamicin-related compounds using injected samples of only a few picograms. Under the described conditions, all analytes were eluted in less than 10 min and the LC-MS analyses exhibited excellent stability and linearity. The method's effectiveness was evaluated by analyzing commercial gentamicin batches and in-house formulations. When the PGC chromatographic system was coupled to an evaporative light scattering detector, detection limits of 40-70 ng were achieved for various major gentamicin components. The chromatographic method was applied on a semi preparative scale to purify the five major components. PMID- 26282487 TI - Recent advances in biosensing using magnetic glyconanoparticles. AB - In this critical review we discuss the most recent advances in the field of biosensing applications of magnetic glyconanoparticles. We first give an overview of the main synthetic routes to obtain magnetic-nanoparticle-carbohydrate conjugates and then we highlight their most promising applications for magnetic relaxation switching sensing, cell and pathogen detection, cell targeting and magnetic resonance imaging. We end with a critical perspective of the field, identifying the main challenges to be overcome, but also the areas where the most promising developments are likely to happen in the coming decades. PMID- 26282488 TI - Transrectal Rigid-Hybrid Natural Orifice Translumenal Endoscopic Sigmoidectomy for Diverticular Disease: A Prospective Cohort Study. AB - BACKGROUND: Our goal was to evaluate the feasibility of transrectal rigid hybrid natural orifice translumenal endoscopic surgery (NOTES) sigmoidectomy (trNS) in a series of consecutive prospective patients with diverticular disease. The NOTES for left colectomy offers patients reduced pain and easier recovery. Limited data are available for trNS, which is considered safe for various indications. However, the technique is not standardized, and patients in the reported series are highly selected. STUDY DESIGN: Patients scheduled for trNS were entered into a prospective registry on an intention-to-treat basis. The primary endpoint was trNS feasibility, and secondary endpoints were morbidity, pain, length of stay, and inflammatory response. A medial-to-lateral dissection with full mobilization of the splenic flexure and total intracorporeal anastomosis was performed. The rectum was covered with a wound protector for transrectal extraction. RESULTS: Of 95 elective sigmoidectomies, 81% (n = 77) were enrolled for either transvaginal NOTES resection (n = 37) or trNS (n = 40). There was no difference in body mass index or indication between patients undergoing laparoscopic-assisted sigmoidectomy (LAS), transvaginal resection, or trNS, although trNS patients were younger. Mainly because of a mismatch of bulky specimen and narrow pelvis, 17.5% of trNS were converted to LAS. Major morbidity was 10%, including 2 septic complications. During the study, the anastomosis technique was changed from double stapled end-to-end to side-to-end anastomosis. CONCLUSIONS: Transrectal rigid hybrid natural orifice translumenal endoscopic sigmoidectomy is feasible and safe in a high proportion of unselected consecutive patients with diverticular disease undergoing elective treatment. Intracorporeal side-to-end anastomosis is the preferred technique, and trNS should be offered for elective sigmoidectomy presupposing advanced laparoscopic experience. PMID- 26282489 TI - Preclinical drug metabolism and pharmacokinetics of salinomycin, a potential candidate for targeting human cancer stem cells. AB - There has been a search for new anticancer agents to treat cancer resistance throughout the globe. Salinomycin (SAL), a broad spectrum antibiotic and a coccidiostat has been found to counter tumour resistance and kill cancer stem cells with better efficacy than the existing chemotherapeutic agents; paclitaxel and doxorubicin. This refocused its importance for treatment of human cancers. In this study, we studied the in vitro drug metabolism and pharmacokinetic parameters of SAL. SAL undergoes rapid metabolism in liver microsomes and has a high intrinsic clearance. SAL metabolism is mainly mediated by CYP enzymes; CYP3A4 the major enzyme metabolising SAL. The percent plasma protein binding of SAL in human was significantly lower as compared to mouse and rat plasma. CYP inhibition was carried out by chemical inhibition and recombinant enzyme studies. SAL was found to be a moderate inhibitor of CYP2D6 as well as CYP3A4. As CYP3A4 was the major enzyme responsible for metabolism of SAL, in vivo pharmacokinetic study in rats was done to check the effect of concomitant administration of Ketoconazole (KTC) on SAL pharmacokinetics. KTC, being a selective CYP3A4 inhibitor increased the systemic exposure of SAL significantly to 7-fold in AUC0 alpha and 3-fold increase in Cmax of SAL in rats with concomitant KTC administration. PMID- 26282490 TI - Dihydrotanshinone I inhibits the translational expression of hypoxia-inducible factor-1alpha. AB - The hypoxia-inducible factor-1 (HIF-1) has been known to be correlated to the adaptation and proliferation of tumor cells; therefore HIF-1 has become an important target in the development of anticancer drugs. Dihydrotanshinone I (DHTS) is a phenanthrenequinone compound from Salvia miltiorrhiza Bunge, which has been used in oriental medicine for its antitumor activities. However, the mechanisms by which DHTS inhibits tumor growth are not fully understood. We here demonstrated the effect of DHTS on hypoxia-inducible factor-1 (HIF-1) activation. DHTS dose-dependently decreased the hypoxia-induced accumulation and activation of HIF-1alpha protein. Further analysis revealed that DHTS inhibited HIF-1alpha protein synthesis, without affecting the expression level of HIF-1alpha mRNA or degradation of HIF-1alpha protein. Moreover, the phosphorylation levels of mammalian target of rapamycin (mTOR), extracellular signal-regulated kinase-1/2 (ERK1/2), ribosomal protein S6 kinase (p70S6K), eIF4E binding protein-1 (4E-BP1), and eukaryotic initiation factor 4E (eIF4E) were dose-dependently suppressed by DHTS, but no significant effect on total protein levels was observed. Furthermore, DHTS prevented hypoxia-induced expression of HIF-1 target genes and flow cytometric analysis indicated that DHTS induced G1 phase arrest in HeLa cell. In vivo studies further confirmed the inhibitory effect of DHTS on the expression of HIF-1alpha proteins, leading to a decrease in growth of HeLa cells in a xenograft tumor model. These results show that DHTS inhibited HIF-1alpha protein synthesis by downregulating the mTOR/p70S6K/4E-BP1 and MEK/ERK pathways. These conclusions suggest that DHTS is an effective inhibitor of HIF-1 and provide new perspectives into the mechanism of its anticancer activity. PMID- 26282491 TI - Structurally related ganoderic acids induce apoptosis in human cervical cancer HeLa cells: Involvement of oxidative stress and antioxidant protective system. AB - Ganoderic acids (GAs) produced by Ganoderma lucidum possess anticancer activities with the generation of reactive oxygen species (ROS). However, the role of oxidative stress in apoptotic process induced by GAs is still undefined. In this study, the effects of four structurally related GAs, i.e. GA-T, GA-Mk, and two deacetylated derivatives of GA-T (GA-T1 and GA-T2) on the antioxidant defense system and induced apoptosis in cervical cancer cells HeLa were investigated in vitro. Our results indicated that the tested GAs (5-40 MUM) induced apoptotic cell death through mitochondrial membrane potential decrease and activation of caspase-9 and caspase-3. Furthermore, GAs increased the generation of intracellular ROS and attenuated antioxidant defense system by decreasing glutathione (GSH) level, superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities. The above effects were remarkably blocked by the exogenous antioxidants, i.e. N-acetylcysteine, catalase and diphenyleneiodonium chloride. The potency of the four GAs toward induced apoptosis, generation of ROS and suppression of antioxidant defense system was in the order of: GA-T > GA-Mk ~ GA T1 > GA-T2 in HeLa cells. These findings suggest that GAs induced mitochondria dependent cell apoptosis in HeLa cells are mediated via enhancing oxidative stress and depressing antioxidant defense. Additionally, the acetylation of hydroxyl groups in GAs may contribute to their pro-oxidant activities and cytotoxicity, which is helpful to the development of novel chemotherapy agents. PMID- 26282492 TI - Autologous bone marrow cell transplantation in acute spinal cord injury--an Indian pilot study. AB - STUDY DESIGN: Phase- I/II, prospective, randomized, single-blind, controlled pilot study. PRIMARY OBJECTIVE: To determine the safety and feasibility of autologous bone marrow transplantation in patients with acute spinal cord injury (SCI) via two routes of transplantation as compared with controls. SETTING: Indian Spinal Injuries Center, New Delhi. METHODS: Twenty-one subjects with acute, American Spinal Injury Association Impairment Scale (AIS) A (complete), traumatic SCI with neurological level T1-T12, were recruited and randomized into three groups of seven subjects each. Two groups underwent cell transplantation through the intrathecal or intralesional route, whereas the third served as control. Participants were assessed at baseline and followed up at 6 months and 12-months post enrollment. Safety and tolerability were evaluated by monitoring for any adverse events. Efficacy was assessed through neurological, functional and psychological evaluation, as well as through electrophysiological studies and urodynamics. RESULTS: Surgery was tolerated well by all participants. There were no significant adverse events attributable to the procedure. There was no significant improvement in the neurological, electrophysiological or urodynamic efficacy variables. A statistically significant improvement in functional scores as evaluated by the Spinal Cord Independence Measure and International Spinal Cord Injury Scale was observed in all groups. CONCLUSIONS: The procedure is safe and feasible in AIS A participants with thoracic-level injuries at 12-months follow-up. No efficacy could be demonstrated that could be attributed to the procedure. PMID- 26282493 TI - A paradigm of galvanic vestibular stimulation diminishes the soleus muscle H reflex in healthy volunteers. AB - STUDY DESIGN: In this study, we explored how galvanic vestibular stimulation can modify the soleus H-reflex (Hoffman reflex), that is, the excitability of the spinal cord circuits, in healthy humans. OBJECTIVES: Our aim was to demonstrate H reflex amplitude modulation caused by changing the duration and the intensity of the anodal galvanic vestibular stimulation. Therefore, we measured H-reflex before and after applied vestibular stimulation. SETTINGS: This study was conducted in Rehabilitation Clinic, Belgrade, Serbia. METHODS: The measurements were performed on 5 male volunteers aged 22-30 years. Anodal galvanic stimulation was applied on the right mastoid in prone position. H-reflex was elicited by nervus tibialis stimulation and measured from the right soleus muscle. In three subjects, trains of weak and strong galvanic stimuli (1, 5 and 9) were applied. In two subjects, only a train of 9 strong stimuli was applied. RESULTS: A statistically significant decrease of the H-reflex amplitude after anodal galvanic stimulation was demonstrated in all subjects. The percentage of H-reflex amplitude diminution was between 6 and 18 in subjects with weak and strong stimuli and 5 and 6 in subjects with only 9 strong stimuli. CONCLUSION: We intend to use this paradigm of stimulation to explore whether the vestibulospinal function exists after spinal cord injury (SCI). If it exists, it can be used to influence the preserved spinal cord circuits after SCI. SPONSORSHIP: One of the authors (Nadica Miljkovic) was partly supported by the Ministry of education, science and technological development, Republic of Serbia, grant OS175016. PMID- 26282494 TI - Response to 'Randomised controlled trials do not always give the results we want but that doesn't mean we should abandon randomised controlled trials'. PMID- 26282495 TI - Shoulder kinetics and ultrasonography changes after performing a high-intensity task in spinal cord injury subjects and healthy controls. AB - STUDY DESIGN: This is a prospective and comparative study between two groups. OBJECTIVES: The objective of this study was to compare the changes in shoulder joint forces and their moments, as well as any possible ultrasound changes, when subjects with spinal cord injury (SCI) and healthy controls (CG) undertake a high intensity manual wheelchair propulsion test. SETTING: This study was conducted in an inpatient SCI rehabilitation center. METHODS: A group of 22 subjects with SCI at level T2 or below who use a manual wheelchair (MWU), categorized as AIS grade A or B, were compared with a CG of 12 healthy subjects. Subjects in each group performed a high-intensity wheelchair propulsion test. The variables analyzed were shoulder joint forces and the moments at the beginning and at the end of the test. Ultrasound variables before and after the propulsion test were also analyzed. Correlations were also drawn between the ultrasonography and demographic variables. RESULTS: In both groups, peak shoulder forces and moments increased after the test in almost all directions. No differences in the ultrasound parameters were found. A greater long-axis biceps tendon thickness (LBTT) was associated with more shoulder pain according to WUSPI or VAS (r=0.428, P<0.05 and r=0.452, P<0.05, respectively). CONCLUSIONS: Shoulder joint forces and moments increase after an intense propulsion task. In subjects with SCI, these increases center on forces with less chance of producing subacromial damage. No changes are produced in ultrasonography variables, whereas a poorer clinical and functional evaluation of the shoulder of the MWUs appears to be related to a thicker long-axis biceps tendon. PMID- 26282496 TI - The role of p38MAPK signal pathway in the neuroprotective mechanism of limb postconditioning against rat cerebral ischemia/reperfusion injury. AB - It has been reported that remote ischemic postconditioning was able to protect from a harmful ischemia occurring in brain. In the present study, we investigated the role of p38 MAPK signal pathway in the process of neuroprotection and anti apoptosis following remote limb ischemic postconditioning on rat focal cerebral ischemia/reperfusion (I/R) model. Male Sprague-Dawley rats were divided randomly into four groups: the sham-operated group, I/R group, limb ischemic postconditioning (LPostC) group, and LPostC+SB203580 (p38 MAPK inhibitor) group. Focal ischemia was induced by transient middle cerebral artery occlusion. Limb ischemic postconditioning was implemented by brief cycles of femoral artery occlusion. At 24h after modeling, we analyzed the neurological deficit score, assessed the cerebral tissue morphology by H-E staining, and evaluated neuronal apoptosis by TUNEL staining. The protein expression levels of p-p38 or p-ATF2 (phospho-activating transcription factor 2) in the penumbra region were detected by western blotting or immunohistochemical staining. Our findings revealed that LPostC relieved cerebral ischemia/reperfusion injury by decreasing neurological score, improving neuronal morphological changes in the ischemic penumbra area, and reducing neuronal apoptosis. In addition, LPostC or LPostC+SB203580 attenuated the increase in p-p38 and p-ATF2 levels in ischemia/reperfusion brain tissue. These results indicate that the protective effects of LPostC against cerebral I/R injury may be related to the attenuation of neuronal apoptosis and the suppression of p38 MAPK-ATF2 pathway. PMID- 26282497 TI - Confirming Sterility of an Autoclaved Infected Femoral Component for Use in an Articulated Antibiotic Knee Spacer: A Pilot Study. AB - Antibiotic spacer designs have proven effective at eradicating infection during a two-stage revision arthroplasty. Temporary reuse of the steam-sterilized femoral component and a new all poly tibia component has been described as an effective articulating antibiotic spacer, but sterility concerns persist. Six explanted cobalt chrome femurs from patients with grossly infected TKA's and six stock femurs inoculated with different bacterial species were confirmed to be bacteria free after autoclaving under a standard gravity-displacement cycle. The effect of steam sterilization on cobalt chrome fragments contaminated with MRSA biofilm was analyzed microscopically to quantify remaining biofilm. The autoclave significantly reduced the biofilm burden on the cobalt chrome fragments. This study confirmed sterility of the femur after a standard gravity-displacement cycle (132 degrees C, 27 PSIG, 10 minutes). PMID- 26282498 TI - Low Infection Rates in Total Knee Arthroplasty in End Stage Renal Failure Patients. AB - End stage renal failure is considered a risk factor for postoperative infection and many surgeons are cautious in offering this group of patients total knee arthroplasty for symptomatic osteoarthritis. In this retrospective study, 16 total knee arthroplasties were performed in 13 patients and each case was followed up for an average of 5.1 years. We report no cases of infection and also an overall improvement in multiple validated outcome measures. There were, however, 2 cases of periprosthetic loosening. As the patients in our series were generally younger and none was diagnosed with stroke or peripheral vascular disease at the time of surgery, we believe that careful patient selection is key to reducing infection rates in this challenging group of patients. PMID- 26282499 TI - Accuracy of Component Positioning in 1980 Total Hip Arthroplasties: A Comparative Analysis by Surgical Technique and Mode of Guidance. AB - The purpose of this multi-surgeon study was to assess and compare the accuracy of acetabular component placement, leg length discrepancy (LLD), and global offset difference (GOD) between six different surgical techniques and modes of guidance in total hip arthroplasty (THA). A total of 1980 THAs met inclusion criteria. Robotic- and navigation-guided techniques were more consistent than other techniques in placing the acetabular cup into Lewinnek's safe zone (P<0.005 and P<0.05, respectively). Robotic-guided surgery was more consistent than other techniques in placing the acetabular component within Callanan's safe zone (P<0.005). No statistically significant differences were found between groups in the frequency of patients with excessive LLD. Clinically significant differences between groups were not found in the frequency of patients with excessive GOD. Level of Evidence: IV. PMID- 26282500 TI - Analysis and classification of errors made by teams during neonatal resuscitation. AB - AIM: The Neonatal Resuscitation Program (NRP) algorithm serves as a guide to healthcare professionals caring for neonates transitioning to extrauterine life. Despite this, adherence to the algorithm is challenging, and errors are frequent. Information-dense, high-risk fields such as air traffic control have proven that formal classification of errors facilitates recognition and remediation. This study was performed to determine and characterize common deviations from the NRP algorithm during neonatal resuscitation. METHODS: Audiovisual recordings of 250 real neonatal resuscitations were obtained between April 2003 and May 2004. Of these, 23 complex resuscitations were analyzed for adherence to the contemporaneous NRP algorithm and scored using a novel classification tool based on the validated NRP Megacode Checklist. RESULTS: Seven hundred eighty algorithm driven tasks were observed. One hundred ninety-four tasks were completed incorrectly, for an average error rate of 23%. Forty-two were errors of omission (28% of all errors) and 107 were errors of commission (72% of all errors). Many errors were repetitive and potentially clinically significant: failure to assess heart rate and/or breath sounds, improper rate of positive pressure ventilation, inadequate peak inspiratory and end expiratory pressures during ventilation, improper chest compression technique, and asynchronous PPV and CC. CONCLUSIONS: Errors of commission, especially when performing advanced life support interventions such as positive pressure ventilation, intubation, and chest compressions, are common during neonatal resuscitation and are sources of potential harm. The adoption of error reduction strategies capable of decreasing cognitive and technical load and standardizing communication - strategies common in other industries - should be considered in healthcare. PMID- 26282501 TI - Direct UV photolysis of selected pharmaceuticals, personal care products and endocrine disruptors in aqueous solution. AB - Pharmaceuticals and personal care products (PPCPs), and endocrine disrupting compounds (EDCs) are micropollutants of emerging concern that have been detected in the aquatic environment and in some cases, in drinking water at nanogram per liter levels. The goal of this study was to evaluate the removal of 15 model PPCPs and EDCs from water by direct UV photolysis, using either low (LP)-or medium (MP) -pressure mercury vapor arc lamps. Some of the model compounds are either weak bases or weak acids, and therefore, the pKa values were determined or confirmed for those compounds using spectrophotometric titrations. The molar absorption coefficients of ionized and non-ionized forms were also determined. The quantum yields at 253.7 nm in phosphate buffer solutions of pH 7.2 were determined to be 0.033 +/- 0.004 for sulfamethoxazole, 0.0035 +/- 0.0008 for sulfachloropyridazine, 0.006 +/- 0.002 for acetaminophen, 0.34 +/- 0.07 for triclosan, 0.35 +/- 0.14 for estrone, 0.08 +/- 0.05 for 17alpha-ethinylestradiol, 0.086 +/- 0.012 for ibuprofen. The quantum yield for 4-n-nonylphenol photolysis at 253.7 nm varied with the initial concentration from 0.32 +/- 0.08 at 23 MUg/L to 0.092 +/- 0.006 at 230 MUg/L. The pseudo-first order rate constants determined for direct photolysis at 253.7 nm of the studied micropollutants followed the order: triclosan ~ sulfamethoxazole >> 4-n-nonylphenol ~ sulfachloropyridazine ~ estrone > acetaminophen ~ 17alpha-ethinylestradiol ~ ibuprofen. In contrast to the results observed for the monochromatic radiation (LP lamp), all 15 model compounds photolyzed under exposure to the broadband radiation emitted by the MP lamp. PMID- 26282502 TI - Bioinformatics analysis of microRNA comprehensive regulatory network in congenital microtia. AB - PURPOSE: This study was aimed to reveal the involvement of miRNAs in the progression of microtia by bioinformatics analyses. METHODS: The data in this study came from the paper of Li et al. who analyzed the microRNA (miRNA) expression profiling between congenital microtia and normal controls. Based on the 11 identified differentially expressed miRNAs, we predicted the target genes, long non-coding RNAs (lncRNA) and transcription factors (TFs). Then we constructed the miRNAs-centered comprehensive regulatory network. In addition, we performed functional enrichment analysis to analyze the functions of target genes. RESULTS: From the miRNAs comprehensive regulatory network, we found that has-miR-203 regulated a large number of target genes and lncRNAs, including suppressor of cytokine signaling 3 (SOCS3) and metastasis associated in lung adenocarcinoma transcript 1 (MALAT1). The has-miR-185, has-miR-451 and has-miR 200c were regulated by a host of TFs including signal transducer and activator of transcription 1 (STAT1) and STAT2. Additionally, the target genes of hsa-miR-486 5p were mainly enriched in 17 Gene Ontology terms and target genes of has-miRNA 203 were enriched in 6 pathways. CONCLUSIONS: The expression of has-miR-203, has miR-200c and has-miR-451 were significantly different in microtia. Target gene of SOCS3, TFs of STAT1 and STAT2, and lncRNA of MALAT1 may play important roles in the development of the external ear. PMID- 26282503 TI - Propranolol-responsive cranial nerve palsies in a patient with PHACES syndrome. AB - PHACES syndrome is a neurocutaneous disorder characterized by the presence of segmental hemangiomas with associated anomalies of the posterior fossa, cerebral vasculature, cardiovascular system, eyes, and ventral or midline structures. We present the first case of propranolol-responsive congenital trigeminal and facial nerve palsies secondary to an intracranial hemangioma in a patient with PHACES syndrome. PMID- 26282504 TI - Working memory, short-term memory and reading proficiency in school-age children with cochlear implants. AB - OBJECTIVE: The objective of the study was to examine short-term memory and working memory through both visual and auditory tasks in school-age children with cochlear implants. The relationship between the performance on these cognitive skills and reading as well as language outcomes were examined in these children. METHODS: Ten children between the ages of 7 and 11 years with early-onset bilateral severe-profound hearing loss participated in the study. Auditory and visual short-term memory, auditory and visual working memory subtests and verbal knowledge measures were assessed using the Woodcock Johnson III Tests of Cognitive Abilities, the Wechsler Intelligence Scale for Children-IV Integrated and the Kaufman Assessment Battery for Children II. Reading outcomes were assessed using the Woodcock Reading Mastery Test III. RESULTS: Performance on visual short-term memory and visual working memory measures in children with cochlear implants was within the average range when compared to the normative mean. However, auditory short-term memory and auditory working memory measures were below average when compared to the normative mean. Performance was also below average on all verbal knowledge measures. Regarding reading outcomes, children with cochlear implants scored below average for listening and passage comprehension tasks and these measures were positively correlated to visual short term memory, visual working memory and auditory short-term memory. Performance on auditory working memory subtests was not related to reading or language outcomes. CONCLUSIONS: The children with cochlear implants in this study demonstrated better performance in visual (spatial) working memory and short-term memory skills than in auditory working memory and auditory short-term memory skills. Significant positive relationships were found between visual working memory and reading outcomes. The results of the study provide support for the idea that WM capacity is modality specific in children with hearing loss. Based on these findings, reading instruction that capitalizes on the strengths in visual short term memory and working memory is suggested for young children with early-onset hearing loss. PMID- 26282505 TI - Safety of surgery for neonatal congenital diaphragmatic hernia as reflected by arterial blood gas monitoring: thoracoscopic versus open repair. AB - PURPOSE: We monitored arterial blood gases during thoracoscopic (TR) and open repair (OR) of congenital diaphragmatic hernia (CDH) to assess the safety of intraoperative hypercapnia and acidosis. METHODS: We reviewed 30 neonatal CDH cases (OR = 10, TR = 20) diagnosed prenatally or within 6 h of birth at out institution from 2002 to 2014 not requiring inhaled nitric oxide (NO) intraoperatively. OR, routine until 2006 was replaced by TR in 2007. All subjects were managed identically. RESULTS: Five TR cases requiring conversion to OR were excluded. Prenatal diagnosis, gestational age at birth, gender, birth weight, and side of CDH were similar. Preoperative PaCO2 and pH were not significantly different. However, while intraoperative increase in mean PaCO2 (38.8-62.8 mmHg; p < 0.01) and decrease in mean pH (7.44-7.25; p < 0.01) were significant in TR, intraoperative PaCO2 was <70 mmHg in 12/15 cases and intraoperative pH was >7.20 in 11/15 cases. Both PaCO2 and pH reverted to normal on completion of surgery; pre- and postoperative results were comparable. There were no postoperative complications. CONCLUSIONS: It would appear that neonatal cases of CDH not requiring NO can tolerate TR, despite transient reversible deterioration in acid/base balance, indicating that TR is safe for the treatment of selected cases of CDH. PMID- 26282506 TI - Refining the intraoperative measurement of the distal intrapancreatic part of a choledochal cyst during laparoscopic repair allows near total excision. AB - During surgery for choledochal cyst (CC), any intrapancreatic CC (IPCC) must also be excised to prevent postoperative pancreatitis and stone formation. We report our technique for laparoscopic total IPCC excision (n = 16; mean age 6.0 years). We insert a fine ureteroscope with a light source into the opened CC through an extra 3.9-mm trocar placed in the epigastrium through a minute incision to identify the pancreatic duct orifice. By pulling the end of the ureteroscope emerging from the trocar gently to withdraw the tip from the pancreatic duct to where distal dissection was ceased under laparoscopic view, the IPCC can be measured. If longer than 5 mm, the distal CC is dissected further caudally until it is less than 5 mm. For accuracy, the distal CC is elevated with a suture that is exteriorized and clamped to provide constant traction. The IPCC was able to be measured in 11/16 (68 %). Initial lengths measured were 3-10 mm (5.2 +/- 2.7 mm). Final IPCC were all 5 mm or less. Surgery was uncomplicated without any pancreatic duct injury and postoperative recovery was unremarkable. Follow-up MRI at 32 months showed no IPCC in any case. Measuring the IPCC enables total CC excision, thus reducing the potential for postoperative complications. PMID- 26282507 TI - Assessing the effect of data pretreatment procedures for principal components analysis of chromatographic data. AB - Following publication of the National Academy of Sciences report "Strengthening Forensic Science in the United States: A Path Forward", there has been increasing interest in the application of multivariate statistical procedures for the evaluation of forensic evidence. However, prior to statistical analysis, variance from sources other than the sample must be minimized through application of data pretreatment procedures. This is necessary to ensure that subsequent statistical analysis of the data provides meaningful results. The purpose of this work was to evaluate the effect of pretreatment procedures on multivariate statistical analysis of chromatographic data obtained for a reference set of diesel fuels. Diesel was selected due to its chemical complexity and forensic relevance, both for fire debris and environmental forensic applications. Principal components analysis (PCA) was applied to the untreated chromatograms to assess association of replicates and discrimination among the different diesel samples. The chromatograms were then pretreated by sequentially applying the following procedures: background correction, smoothing, retention-time alignment, and normalization. The effect of each procedure on association and discrimination was evaluated based on the association of replicates in the PCA scores plot. For these data, background correction and smoothing offered minimal improvement, whereas alignment and normalization offered the greatest improvement in the association of replicates and discrimination among highly similar samples. Further, prior to pretreatment, the first principal component accounted for only non-sample sources of variance. Following pretreatment, these sources were minimized and the first principal component accounted for significant chemical differences among the diesel samples. These results highlight the need for pretreatment procedures and provide a metric to assess the effect of pretreatment on subsequent multivariate statistical analysis of complex data. PMID- 26282508 TI - Demonstrating the effect of forensic firearm countermeasures: Bullet characteristics generated due to barrel modifications. AB - Forensic awareness and the declining availability of firearms have resulted in an increase in the use of modified and re-activated firearms in crime. Although some modifications are undertaken to simply acquire a functioning firearm, others are perpetrated as a direct forensic countermeasure to prevent the association between a firearm and a crime. This article describes the effects of these modifications on bullet striation patterns imparted from the barrel to a fired bullet. The key results indicated that the investigated modifications display assessable characteristics. The use of an oversized barrel imparted striations consistent with firing with the absence of typical rifling. Subsequent or consecutively fired bullets possessed striation variations, with the first showing the least evidence of striations. The application of a choke resulted in more obvious bullet elongation compared to a smoothbore barrel. The restriction caused merging of lands and groves of the imparted rifling and obscured their usual definition. Effects of breech adaption were also characterised by observing the buckling and enlargement of the cartridge case. This deformity of the cartridge case was most evident when the barrel pressure increased due to the presence of the choke. From this study it was evident that unique characteristic impressions associated with different modifications most commonly found in criminal investigations can be utilised by a forensic expert and impart significant intelligence to an investigation. PMID- 26282509 TI - A new p-dimethylaminocinnamaldehyde reagent formulation for the photoluminescence detection of latent fingermarks on paper. AB - Dimethylaminocinnamaldehyde was re-evaluated as a wet contact reagent for the treatment of latent fingermarks on porous substrates. A new formulation (consisting of 0.028 g p-dimethylaminocinnamaldehyde, 0.84 mL glacial acetic acid, 6.2 mL ethyl acetate and 0.993 L 40-60 degrees C petroleum spirits) provides quick, sensitive and robust luminescent ridge detail within 3 h of treatment on both plain and thermal paper. Comparisons to existing formulations indicate improved visualisation and/or a more efficient process. PMID- 26282510 TI - Liquid chromatography with tandem mass spectrometry for the determination of flufenoxuron in blood using automatic solid phase extraction and its application to a fatal case of flufenoxuron poisoning. AB - A liquid chromatography/tandem mass spectrometry method with solid phase extraction for the detection and the quantitation of flufenoxuron in an aliquot of blood was developed and validated. Flufenoxuron belongs to a benzoylurea insecticide and is the active ingredient of CascadeTM. The analyte in postmortem specimens was extracted by solid-phase extraction with Bond Elut Certify cartridge. After the elution layer was evaporated, the residue was reconstituted with 70% methanol for LC/MS/MS analysis. Separations were carried out on a Synergi((r)) 2.5u Fusion-RP 100 A column with column temperature kept at 40 degrees C at a flow rate of 0.4 mL/min. The mobile phase was composed of 5mM ammonium formate in 10% methanol and 5 mM ammonium formate in 90% methanol using gradient elution. A triple quadruple mass spectrometer equipped with an electrospray ionization source operated in a positive ion mode with selective reaction monitoring mode. Atrazine-d5 was used as internal standard. The assay was linear over 0.02-1.0 mg/L (r(2)=0.999). Limit of detection (LOD) and limit of quantitation (LOQ) in blood were 0.009 mg/L (S/N=3) and 0.02 mg/L (S/N=10), respectively. The accuracy and the precision were <14.9% of bias% and <8.1% of CV%, which are acceptable criteria according to toxicology laboratory guidelines. Relative recoveries with 0.02, 0.1 and 1.0mg/L (in blood) were 112.3%, 101.2% and 111.0% (n=5), respectively. The developed method was applied in forensic toxicology to determine flufenoxuron in postmortem specimens in a fatal case of flufenoxuron intoxication in a 48-year-old-man who was found dead on bed in a small room after vomiting on the floor. The postmortem heart blood, peripheral blood and gastric contents were analyzed for flufenoxuron with the result of 6.3 mg/L in heart blood, 3.2 mg/L in peripheral blood and 30.6 mg/kg in gastric contents, respectively. The concentration ratio of the heart/peripheral blood of flufenoxuron was 2.0, and the ratio of gastric contents/peripheral blood was 9.4, suggesting possible postmortem redistribution and there may be a massive amount of flufenoxuron orally ingested. This case study is the first report of lethal concentrations of flufenoxuron in postmortem specimens. PMID- 26282511 TI - A comparison between atmospheric/humidity and vacuum cyanoacrylate fuming of latent fingermarks. AB - A number of pseudo-operational trials were set up to compare the atmospheric/humidity and vacuum cyanoacrylate fuming processes on plastic carrier bags. The fuming processes were compared using two-step cyanoacrylate fuming with basic yellow 40 (BY40) staining and a one-step fluorescent cyanoacrylate fuming, Lumicyano 4%. Preliminary work using planted fingermarks and split depletions were performed to identify the optimum vacuum fuming conditions. The first pseudo operational trial compared the different fuming conditions (atmospheric/humidity vs. vacuum) for the two-step process where an additional 50% more marks were detected with the atmospheric/humidity process. None of the marks by the vacuum process could be observed visually; however, a significant number of marks were detected by fluorescence after BY40 staining. The second trial repeated the same work in trial 1 using the one-step cyanoacrylate process, Lumicyano at a concentration of 4%. Trial 2 provided comparable results to trial 1 and all the items were then re-treated with Lumicyano 4% at atmospheric/humidity conditions before dyeing with BY40 to provide the sequences of process A (Lumicyano 4% atmospheric-Lumicyano 4% atmospheric-BY40) and process B (Lumicyano 4% vacuum Lumicyano 4% atmospheric-BY40). The number of marks (visual and fluorescent) was counted after each treatment with a substantial increase in the number of detected marks in the second and third treatments of the process. The increased detection rate after the double Lumicyano process was unexpected and may have important implications. Trial 3 was performed to investigate whether the amount of cyanoacrylate and/or fuming time had an impact on the results observed in trial 2 whereas trial 4 assessed if the double process using conventional cyanoacrylate, rather than Lumicyano 4%, provided an increased detection rate. Trials 3 and 4 confirmed that doubling the amount of Lumicyano 4% cyanoacrylate and fuming time produced a lower detection rate than the double process with Lumicyano 4%. Furthermore, the double process with conventional cyanoacrylate did not provide any benefit. Scanning electron microscopy was also performed to investigate the morphology of the cyanoacrylate polymer under different conditions. The atmospheric/humidity process appears to be superior to the vacuum process for both the two-step and one-step cyanoacrylate fuming, although the two step process performed better in comparison to the one-step process under vacuum conditions. Nonetheless, the use of vacuum cyanoacrylate fuming may have certain operational advantages and its use does not adversely affect subsequent cyanoacrylate fuming with atmospheric/humidity conditions. PMID- 26282512 TI - The harmful chemistry behind "krokodil": Street-like synthesis and product analysis. AB - "Krokodil" is the street name for a drug, which has been attracting media and researchers attention due to its increasing spread and extreme toxicity. "Krokodil" is a homemade injectable mixture being used as a cheap substitute for heroin. Its use begun in Russia and Ukraine, but it is being spread throughout other countries. The starting materials for "krokodil" synthesis are tablets containing codeine, caustic soda, gasoline, hydrochloric acid, iodine from disinfectants and red phosphorus from matchboxes, all of which are easily available in a retail market or drugstores. The resulting product is a light brown liquid that is injected without previous purification. Herein, we aimed to understand the chemistry behind "krokodil" synthesis by mimicking the steps followed by people who use this drug. The successful synthesis was assessed by the presence of desomorphine and other two morphinans. An analytical gas chromatography-electron impact/mass spectrometry (GC-EI/MS) methodology for quantification of desomorphine and codeine was also developed and validated. The methodologies presented herein provide a representative synthesis of "krokodil" street samples and the application of an effective analytical methodology for desomorphine quantification, which was the major morphinan found. Further studies are required in order to find other hypothetical by-products in "krokodil" since these may help to explain signs and symptoms presented by abusers. PMID- 26282513 TI - Rapid determination of benzodiazepines, zolpidem and their metabolites in urine using direct injection liquid chromatography-tandem mass spectrometry. AB - Benzodiazepines and zolpidem are generally prescribed as sedative, hypnotics, anxiolytics or anticonvulsants. These drugs, however, are frequently misused in drug-facilitated crime. Therefore, a rapid and simple liquid chromatography tandem mass spectrometric (LC-MS/MS) method was developed for identification and quantification of benzodiazepines, zolpidem and their metabolites in urine using deuterium labeled internal standards (IS). Urine samples (120 MUL) mixed with 80 MUL of the IS solution were centrifuged. An aliquot (5 MUL) of the sample solution was directly injected into the LC-MS/MS system for analysis. The mobile phases consisted of water and acetonitrile containing 2mM ammonium trifluoroacetate and 0.2% acetic acid. The analytical column was a Zorbax SB-C18 (100 mm * 2.1 mm i.d., 3.5 MUm, Agilent). The separation and detection of 18 analytes were achieved within 10 min. Calibration curves were linear over the concentration ranges of 0.5-20 ng/mL (zolpidem), 1.0-40 ng/mL (flurazepam and temazepam), 2.5-100 ng/mL (7-aminoclonazepam, 1-hydroxymidazolam, midazolam, flunitrazepam and alprazolam), 5.0-200 ng/mL (zolpidem phenyl-4-carboxylic acid, alpha-hydroxyalprazolam, oxazepam, nordiazepam, triazolam, diazepam and alpha hydroxytriazolam), 10-400 ng/mL (lorazepam and desalkylflurazepam) and 10-100 ng/mL (N-desmethylflunitrazepam) with the coefficients of determination (r(2)) above 0.9971. The dilution integrity of the analytes was examined for supplementation of short linear range. Dilution precision and accuracy were tested using two, four and ten-folds dilutions and they ranged from 3.7 to 14.4% and -12.8 to 12.5%, respectively. The process efficiency for this method was 63.0 104.6%. Intra- and inter-day precisions were less than 11.8% and 9.1%, while intra- and inter-day accuracies were less than -10.0 to 8.2%, respectively. The lower limits of quantification were lower than 10 ng/mL for each analyte. The applicability of the developed method was successfully verified with human urine samples from drug users (n=21). Direct urine sample injection and optimized mobile phases were introduced for simple sample preparation and high-sensitivity with the desired separation. PMID- 26282514 TI - Light generation of intracellular Ca(2+) signals by a genetically encoded protein BACCS. AB - Ca(2+) signals are highly regulated in a spatiotemporal manner in numerous cellular physiological events. Here we report a genetically engineered blue light activated Ca(2+) channel switch (BACCS), as an optogenetic tool for generating Ca(2+) signals. BACCS opens Ca(2+)-selective ORAI ion channels in response to light. A BACCS variant, dmBACCS2, combined with Drosophila Orai, elevates the Ca(2+) concentration more rapidly, such that Ca(2+) elevation in mammalian cells is observed within 1 s on light exposure. Using BACCSs, we successfully control cellular events including NFAT-mediated gene expression. In the mouse olfactory system, BACCS mediates light-dependent electrophysiological responses. Furthermore, we generate BACCS mutants, which exhibit fast and slow recovery of intracellular Ca(2+). Thus, BACCSs are a useful optogenetic tool for generating temporally various intracellular Ca(2+) signals with a large dynamic range, and will be applicable to both in vitro and in vivo studies. PMID- 26282515 TI - Etiologic features and utilization of antiepileptic drugs in people with chronic epilepsy in China: Report from the Epilepsy Cohort of Huashan Hospital (ECoH). AB - PURPOSE: Chronic epilepsy is estimated to affect more than 2 million people in China. However, data of its clinical characteristics was rarely reported in China. In the present study, we summarized the etiologic features and utilization patterns of antiepileptic drugs (AEDs) in people with chronic epilepsy in a tertiary medical center in China. METHODS: We prospectively recruited people with chronic epilepsy treated at the Epilepsy Outpatient Clinic of Huashan Hospital during October 2009 to August 2013. Demographic data, clinical characteristics, AED treatment, epilepsy-associated risk factors and medical history, and results of supplementary examinations of each participant were collected retrospectively via an interviewer-administered questionnaire and confirmed by the medical records. RESULTS: Among 554 people with chronic epilepsy, 58.0% of them were male, 66.8% had focal seizure, and 29.2% had symptomatic cause. Developmental anomalies of cerebral structure (16.7%) and cerebral trauma (16.7%) shared the leading cause of symptomatic epilepsy among children with epilepsy. While cerebral trauma (29.1%) and cerebrovascular disorder (36.4%) were the most common causes in groups of adults and elderly. Fifty percent of participants were taking AED monotherapy. Proportions of people with idiopathic, cryptogenic and symptomatic epilepsy treated by multitherapy were 35%, 46% and 45.6%, respectively. Valproic acid (VPA) was the most frequently utilized AED as monotherapy (32.7%) and within multitherapy (62.5%). SIGNIFICANCE: This hospital based study reported that etiologic features were diverse in different age groups of people with chronic epilepsy. VPA was widely utilized to treat chronic epilepsy in mainland China. PMID- 26282516 TI - Impact of Obesity on Surgical Treatment for Endometrial Cancer: A Multicenter Study Comparing Laparoscopy vs Open Surgery, with Propensity-Matched Analysis. AB - OBJECTIVE: To evaluate the impact of obesity on the outcomes of surgical treatment for endometrial cancer in general and also comparing laparoscopic and open abdominal approach. DESIGN: Retrospective case-control study (Canadian Task Force classification II-1). SETTING: Obstetrics and Gynecology Department, University of Insubria, Varese, Catholic University of the Sacred Heart, Rome, International School of Surgical Anatomy, Sacred Heart Hospital, Negrar, and Sant'Orsola-Malpighi Hospital, Bologna, Italy. PATIENTS: Data of consecutive patients who underwent surgery for endometrial cancer in 4 centers were reviewed. Univariate and multivariable analyses were performed. Adjustment for potential selection bias in surgical approach was made using propensity score (PS) matching. INTERVENTIONS: Laparoscopic or open surgical treatment for endometrial cancer. MEASUREMENTS AND MAIN RESULTS: A total of 1266 patients were included, including 764 in the laparoscopy group and 502 in the open surgery group. A total of 391 patients (30.9%) were obese, including 238 (18.8%) with class I obesity, 89 (7%) with class II obesity, and 64 (5.1%) with class III obesity. The total number of complications, risk of wound complications, and venous thromboembolic events were higher in obese women compared with nonobese women. Blood transfusions, incidence/severity of postoperative complications, and postoperative hospital stay were significantly higher in the open surgery group compared with the laparoscopy group, irrespective of obesity. These differences remained significant in both multivariable analysis and PS-matched analysis. The percentage of patients who received lymphadenectomy declined significantly in patients with BMI >=40 in both the laparoscopy and open surgery groups. Conversions from the initially intended minimally invasive approach to open surgery were 1.1% to 2.2% for women with BMI <40, but increased in those with BMI >=40 (8.6%; p = .05). PS analysis showed a lower complication rate, shorter hospital stay, and greater likelihood of receiving lymphadenectomy in obese women in the laparoscopic group. CONCLUSION: Laparoscopy for endometrial cancer retains its advantages over open surgery, even in obese patients. However, operating on obese patients can be challenging regardless of the surgical approach taken, especially in cases of morbid adiposity. PMID- 26282517 TI - Myofibroblastoma of the mandible in a 3-year-old child. AB - Myofibroblastoma is a rare benign tumor of the head and neck region, which is characterized by a large, rapidly growing, and destructive mass. A 3-year-old boy presented with an 8-week history of a rapidly growing swelling of the right mandible. Examination revealed a firm 13-cm mass occupying the entire right body and ramus of the mandible. The clinical and radiological features were suggestive of a sarcoma. An initial biopsy taken in the referring hospital was inconclusive, and the second biopsy showed a myofibroblastic neoplasm consistent with a desmoplastic fibroma. Progressive tumor growth necessitated a tracheostomy. Right hemimandibulectomy was performed, and the defect was reconstructed with free microvascular fibula flap. Histopathology and immunocytochemistry revealed a myofibroblastoma. This entity differs from other myofibroblasts and fibroblast tumors such as inflammatory myofibroblastic tumor (IMT), myofibroma, and desmoplastic fibroma. The child has been followed up for 2 years. CONCLUSION: Differentiation between myofibroblasts and fibroblastic tumors as well as some malignancies can be challenging. Myofibroblastoma can behave as a malignant neoplasm, and the clinical distinction of this entity lies primarily in its recognition as a benign neoplasm. PMID- 26282518 TI - Cranial base growth in adolescence assessed through cone-beam computerized tomographies--pilot study. AB - OBJECTIVE: To assess growth of the middle/posterior cranial base during adolescence based on landmarks located on serial three-dimensional cone-beam computerized tomography (CBCT) images. MATERIALS AND METHODS: CBCT scans from 62 adolescents (11 to 17 years) at baseline and 12 months were used. Eleven landmarks in the cranial base were identified. Linear landmark distances were compared over the two time points using basic descriptive statistics. Shape analysis was carried out using R (R Foundation for Statistical Computing, Austria). Discrete curves were obtained and aligned via a Procrustes transformation and examined for group dimorphism and longitudinal change. RESULTS: Mean differences between linear distances in the cranial base were within 1mm, apart from the difference between the right and left auditory external meatuses, which was 2.25 mm. No statistically significant longitudinal differences in shape were found in relation to the peak growth period. CONCLUSION: Cranial base growth was minimal over the observation period. There were no differences in terms of the amount and pattern of growth. The cranial base is said to complete most of its growth by age 12, but this has only been verified through two-dimensional studies. Our findings using CBCT confirm this, and support the use of the cranial base as a stable anatomical reference structure for superimpositioning. PMID- 26282520 TI - Physiological correction of lingual dysfunction with the "Tongue Right Positioner": Beneficial effects on the upper airways. AB - Several studies have demonstrated the beneficial role of functional tongue therapy in stabilizing treatments for dental malocclusion and treating sleep disordered breathing (SDB). The aim of this retrospective study was to evaluate the effect on the upper airways of the Tongue Right Positioner device (TRP) used for the correction of atypical swallowing. We analyzed lateral headfilms of 94 orthodontic patients aged between 11 and 17, before the start of treatment and after establishment of mature swallowing, treated with the TRP (TRP group) or by reeducation exercises (control group). In the TRP group, the establishment of mature swallowing occurs twice as fast as in the control group. This led to thinning of the floor of the mouth (-8.38%, P<0.001) linked to anteroposterior enlargement of the pharynx (+10.48%, P<0.01), both probably due to an increase in genioglossal and styloglossal muscle tone and correction of cranio-cervical posture (+2.52%, P<0.01). These results are not dependent on the type of orthodontic treatment. They suggest that the TRP could be used in the treatment of SDB. PMID- 26282522 TI - Digital image analysis of testicular and prostatic ultrasonographic echogencity and heterogeneity in dogs and the relation to semen quality. AB - A semi-automated ultrasonographic method was developed to measure echogenicity and heterogeneity of the testes and prostate gland and relationships of these measures with semen quality were assessed in 43 fertile dogs. The relationship between animal age and body weight upon the volume of the testes, epididymal tail volume and prostate volume were also established. Mean testicular echogenicity was negatively correlated with the percentage of morphologically normal live spermatozoa (more echogenic testes were associated with fewer normal sperm) but not with any other semen quality measure. Mean testicular heterogeneity was positively correlated with the total spermatozoal output (more heterogenous testes, being those with anechoic parenchyma and prominent echogenic stippling, were associated with greater sperm output) but not with any other semen quality measure. There was no relationship between either mean prostatic echogenicity or mean prostatic heterogeneity and any semen quality measure. There was no relationship between age and any testicular or prostatic parameter; however bodyweight was significantly correlated with total testicular volume, total epididymal tail volume and total prostatic volume. Testicular and prostatic ultrasonographic echogenicity and heterogeneity can be objectively assessed using digital image analysis and testicular echogenicity and heterogeneity may be useful adjunct measurements in a breeding soundness examination. PMID- 26282523 TI - A field investigation of a modified intravaginal progesterone releasing device and oestradiol benzoate based ovulation synchronisation protocol designed for fixed-time artificial insemination of Brahman heifers. AB - Pregnancy rates (PR) to fixed-time AI (FTAI) in Brahman heifers were compared after treatment with a traditional oestradiol-based protocol (OPO-8) or a modified protocol (OPO-6) where the duration of intravaginal progesterone releasing device (IPRD) was reduced from 8 to 6 days, and the interval from IPRD removal to oestradiol benzoate (ODB) was increased from 24 to 36 h. Rising 2 yo heifers on Farm A: (n = 238 and n = 215; two consecutive days AI); B (n = 271); and C (n = 393) were allocated to OPO-8 or OPO-6. An IPRD was inserted and 1mg ODB i.m. on Day 0 for OPO-8 heifers and Day 2 for OPO-6 heifers. On Day 8, the IPRD was removed and 500 MUg cloprostenol i.m. At 24h, for OPO-8 heifers, and 36 h, for OPO-6 heifers, post IPRD removal all heifers received 1mg ODB i.m. FTAI was conducted at 54 and 72 h post IPRD removal for OPO-8 and OPO-6 heifers. At Farm A, OPO-6 heifers, AI on the second day, the PR was 52.4% to FTAI (P = 0.024) compared to 36.8% for OPO-8 heifers. However, no differences were found between OPO-8 and OPO-6 protocols at Farm A (first day of AI) (39.9 vs. 35.7%), or Farms B (26.2 vs. 35.4%) and C (43.2% vs. 40.3%). Presence of a corpus luteum at IPRD insertion affected PR to FTAI (43.9% vs. 28.8%; P < 0.001). This study has shown that the modified ovulation synchronisation protocol OPO-6 may be a viable alternative to the OPO-8 protocol for FTAI in B. indicus heifers. PMID- 26282524 TI - Seminal plasma protein profiles of ejaculates obtained by internal artificial vagina and electroejaculation in Brahman bulls. AB - The present study was conducted to investigate if differences exist in the seminal plasma protein profile from mature Brahman bulls using two methods of semen collection: internal artificial vagina (IAV) and electroejaculation (EEJ). Semen was collected four times from three bulls on the same day and parameters were assessed immediately post-collection. Seminal plasma proteins were evaluated by 2-D fluorescence difference gel electrophoresis and identified by mass spectrometry. Semen volume was greater (P < 0.05) for EEJ (4.6 +/- 0.35 mL) than for IAV (1.86 +/- 0.24 mL) but sperm concentration was greater in IAV (1505 +/- 189 * 10(6) sperm/mL) than in EEJ samples (344 +/- 87 * 10(6) sperm/mL). Sperm motility and the percentage of normal sperm were not different between treatments. Total concentration of seminal plasma proteins was greater for samples collected by IAV as compared to EEJ (19.3 +/- 0.9 compared with 13.0 +/- 1.8 mg/mL, P < 0.05; respectively). Based on 2-D gels, 22 spots had a greater volume (P < 0.05) in gels derived from IAV samples, corresponding to 21 proteins identified as transferrin, albumin, epididymal secretory glutathione peroxidase, among others. Thirty-three spots, corresponding to 26 proteins, had a greater volume (P < 0.05) in gels derived from EEJ samples. These proteins were identified as spermadhesin-1, Bovine Sperm Protin 1, 3 and 5 isoforms, angiogenin 1, alpha-1B-glycoprotein, clusterin, nucleobindin-1, cathepsins, spermadhesin Z13, annexins, among others. Thus, proteins in greater amounts in samples obtained by IAV and EEJ were mainly of epididymal origin and accessory sex glands, respectively. PMID- 26282525 TI - The Green Eating Project: web-based intervention to promote environmentally conscious eating behaviours in US university students. AB - OBJECTIVE: To investigate the effectiveness of an online, interactive intervention, referred to as the Green Eating (GE) Project, to motivate university students to adopt GE behaviours. DESIGN: The study was quasi experimental and integrated into courses for credit/extra credit. Courses were randomly stratified into experimental or non-treatment control. The 5-week intervention consisted of four modules based on different GE topics. Participants completed the GE survey at baseline (experimental, n 241; control, n 367) and post (experimental, n 187; control, n 304). The GE survey has been previously validated and consists of Transtheoretical Model constructs including stage of change (SOC), decisional balance (DB: Pros and Cons) and self-efficacy (SE: School and Home) as well as behaviours for GE. Modules contained basic information regarding each topic and knowledge items to assess content learning. SETTING: The GE Project took place at a public university in the north-eastern USA. SUBJECTS: Participants were full-time students between the ages of 18 and 24 years. RESULTS: The GE Project was effective in significantly increasing GE behaviours, DB Pros, SE School and knowledge in experimental compared with control, but did not reduce DB Cons or increase SE Home. Experimental participants were also more likely to be in later SOC for GE at post testing. CONCLUSIONS: The GE Project was effective in increasing GE behaviours in university students. Motivating consumers towards adopting GE could assist in potentially mitigating negative consequences of the food system on the environment. Future research could tailor the intervention to participant SOC to further increase the effects or design the modules for other participants. PMID- 26282526 TI - Dietary Selenium Status Regulates the Transcriptions of Selenoproteome and Activities of Selenoenzymes in Chicken Kidney at Low or Super-nutritional Levels. AB - To determine dietary selenium (Se) status regulates the transcriptions of selenoproteome and activities of selenoenzymes in chicken kidney, 1-day-old chickens received low Se (0.028 mg Se per kg of diet) or super-nutritional Se (3.0 or 5.0 mg Se per kg of diet) in their diets for 8 weeks. It was observed that dietary low or super-nutritional Se did not make renal appearance pathological changes in chicken. Low Se significantly reduced total antioxidant capability (T-AOC), glutathione (GSH) content, but malondialdehyde (MDA) content in the kidney increased and decreased glutathione peroxidase (Gpx) and thioredoxin reductase (TrxR) activity with changes in their mRNA levels. Super nutritional Se (3.0 mg/kg) increased T-AOC and GSH contents then made them reduce, but it reduced MDA content significantly, elevated then reduced Gpx activity, and decreased TrxR activity with changes in their mRNA levels. Dietary low Se downregulated the mRNA expressions of Gpx1-4, Txnrd3, Sepn1, Selw, Sepx1, Selh, and SEPSECS. At super-nutritional Se, most selenoproteins were upregulated in chicken kidney, but Sepp2 and Sep15 was only upregulated in Se excess (5.0 mg/kg) bird. These results indicated that dietary Se status stabilizes normal renal physiology function via regulation of the selenoprotemic transcriptions and selenoenzyme activities in avian. PMID- 26282527 TI - Effect of Tauroursodeoxycholic Acid and 4-Phenylbutyric Acid on Metabolism of Copper and Zinc in Type 1 Diabetic Mice Model. AB - Alternations of copper (Cu) and zinc (Zn) status in diabetes have received a great attention. Tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyric acid (PBA) could alleviate the increased endoplasmic reticulum (ER) stress and prevent insulin resistance. This study aimed to investigate the effect of TUDCA and PBA on metabolism of Cu and Zn in diabetic mice model. Diabetes was induced by streptozotocin in FVB mice treated with and without TUDCA and PBA. Determination of Cu and Zn in tissues and serum by acid digestion was followed by ICP-MS. The renal and serum Cu levels were significantly higher, while the hepatic Cu and Zn levels were significantly decreased in the diabetic mice at 2 weeks and 2 months after diabetes onset. The increase of cardiac Cu together with the decrease of muscular Zn was found in the diabetic mice only at 2 months. Cu levels were positively correlated with Zn in the heart, liver, kidney, muscle, spleen, and serum of diabetic and control mice at both 2 weeks and 2 months. Both PBA and TUDCA reduced serum Zn, and PBA reduced hepatic Cu to normal levels in the diabetic mice at two time points, while PBA normalized serum Cu in the diabetic mice only at 2 months. PBA increased hepatic Zn to normal levels in the diabetic mice at 2 weeks, while it partially increased hepatic Zn in the same group at 2 months. Therefore, maintaining homeostasis of Cu and Zn by TUDCA and PBA in diabetes needs to be received with special attention. PMID- 26282528 TI - Generalized seizures in a neural field model with bursting dynamics. AB - The mechanisms underlying generalized seizures are explored with neural field theory. A corticothalamic neural field model that has accounted for multiple brain activity phenomena and states is used to explore changes leading to pathological seizure states. It is found that absence seizures arise from instabilities in the system and replicate experimental studies in numerous animal models and clinical studies. PMID- 26282536 TI - The exceptionally rich coordination chemistry generated by Schiff-base ligands derived from o-vanillin. AB - Ortho-vanillin became very popular in coordination chemistry because of its Schiff bases, which generate a rich variety of complexes, ranging from oligonuclear species to coordination polymers. Some of these organic molecules are particularly useful in metallosupramolecular chemistry for assembling homo- and heterometallic helicates. The Schiff bases obtained using aminoalcohols open the door to the synthesis of homo- and heterometallic clusters with various nuclearities and surprising topologies of the metal centers. Several relevant structural types are reviewed. The heterobinuclear 3d-3d' and 3d-4f complexes are valuable building-blocks for the synthesis of heterotrimetallic systems. Beyond the richness of this chemistry, the complexes obtained from o-vanillin-based Schiff ligands show interesting properties: magnetism, luminescence, chirality, catalysis, cytotoxicity, and ferroelectricity. This paper reviews recent data that illustrate a very fertile and dynamic research field in coordination chemistry and materials science. PMID- 26282529 TI - Impact of dietary fat on the development of non-alcoholic fatty liver disease in Ldlr-/- mice. AB - The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased in parallel with central obesity and is now the most common chronic liver disease in developed countries. NAFLD is defined as excessive accumulation of lipid in the liver, i.e. hepatosteatosis. The severity of NAFLD ranges from simple fatty liver (steatosis) to non-alcoholic steatohepatitis (NASH). Simple steatosis is relatively benign until it progresses to NASH, which is characterised by hepatic injury, inflammation, oxidative stress and fibrosis. Hepatic fibrosis is a risk factor for cirrhosis and primary hepatocellular carcinoma. Our studies have focused on the impact of diet on the onset and progression of NASH. We developed a mouse model of NASH by feeding Ldlr-/- mice a western diet (WD), a diet moderately high in saturated and trans-fat, sucrose and cholesterol. The WD induced a NASH phenotype in Ldlr-/- mice that recapitulates many of the clinical features of human NASH. We also assessed the capacity of the dietary n-3 PUFA, i.e. EPA (20 : 5,n-3) and DHA (22 : 6,n-3), to prevent WD-induced NASH in Ldlr-/- mice. Histologic, transcriptomic, lipidomic and metabolomic analyses established that DHA was equal or superior to EPA at attenuating WD-induced dyslipidemia and hepatic injury, inflammation, oxidative stress and fibrosis. Dietary n-3 PUFA, however, had no significant effect on WD-induced changes in body weight, body fat or blood glucose. These studies provide a molecular and metabolic basis for understanding the strengths and weaknesses of using dietary n-3 PUFA to prevent NASH in human subjects. PMID- 26282539 TI - Incidence of breast cancer among female survivors of Hodgkin lymphoma: a US population-based trend analysis from 1973 to 2011. PMID- 26282538 TI - Mesenchymal stem cells derived from human induced pluripotent stem cells retain adequate osteogenicity and chondrogenicity but less adipogenicity. AB - INTRODUCTION: Previously, we established a simple method for deriving mesenchymal stem cells (MSCs) from human induced pluripotent stem cells (iPSC-MSCs). These iPSC-MSCs were capable of forming osteogenic structures in scaffolds and nanofibers. The objective of this study is to systematically characterize the mesenchymal characteristics of the iPSC-MSCs by comparing them to bone marrow derived MSCs (BM-MSCs). METHODS: Two iPSC-MSC lines (named as mRNA-iPSC-MSC-YL001 and lenti-iPSC-MSC-A001) and one BM-MSC line were used for the study. Cell proliferation, presence of mesenchymal surface markers, tri-lineage differentiation capability (osteogenesis, chondrogenesis, adipogenesis), and expression of "stemness" genes were analyzed in these MSC lines. RESULTS: The iPSC-MSCs were similar to BM-MSCs in terms of cell morphology (fibroblast-like) and surface antigen profile: CD29+, CD44+, CD73+, CD90+, CD105+, CD11b-, CD14-, CD31-, CD34-, CD45- and HLA-DR-. A faster proliferative capability was seen in both iPSC-MSCs lines compared to the BM-MSCs. The iPSC-MSCs showed adequate capacity of osteogenesis and chondrogenesis compared to the BM-MSCs, while less adipogenic potential was found in the iPSC-MSCs. The iPSC-MSCs and the tri lineage differentiated cells (osteoblasts, chondrocytes, adipocytes) all lack expression of "stemness" genes: OCT4, SOX2, GDF3, CRIPTO, UTF1, DPPA4, DNMT3B, LIN28a, and SAL4. CONCLUSIONS: The MSCs derived from human iPSCs with our method have advanced proliferation capability and adequate osteogenic and chondrogenic properties compared to BM-MSCs. However, the iPSC-MSCs were less efficient in their adipogenicity, suggesting that further modifications should be applied to our method to derive iPSC-MSCs more closely resembling the naive BM-MSCs if necessary. PMID- 26282537 TI - Diagnosis of neglected tropical diseases among patients with persistent digestive disorders (diarrhoea and/or abdominal pain >=14 days): Pierrea multi-country, prospective, non-experimental case-control study. AB - BACKGROUND: Diarrhoea still accounts for considerable mortality and morbidity worldwide. The highest burden is concentrated in tropical areas where populations lack access to clean water, adequate sanitation and hygiene. In contrast to acute diarrhoea (<14 days), the spectrum of pathogens that may give rise to persistent diarrhoea (>=14 days) and persistent abdominal pain is poorly understood. It is conceivable that pathogens causing neglected tropical diseases play a major role, but few studies investigated this issue. Clinical management and diagnostic work up of persistent digestive disorders in the tropics therefore remain inadequate. Hence, important aspects regarding the pathogenesis, epidemiology, clinical symptomatology and treatment options for patients presenting with persistent diarrhoea and persistent abdominal pain should be investigated in multi-centric clinical studies. METHODS/DESIGN: This multi-country, prospective, non experimental case-control study will assess persistent diarrhoea (>=14 days; in individuals aged >=1 year) and persistent abdominal pain (>=14 days; in children/adolescents aged 1-18 years) in up to 2000 symptomatic patients and 2000 matched controls. Subjects from Cote d'Ivoire, Indonesia, Mali and Nepal will be clinically examined and interviewed using a detailed case report form. Additionally, each participant will provide a stool sample that will be examined using a suite of diagnostic methods (i.e., microscopic techniques, rapid diagnostic tests, stool culture and polymerase chain reaction) for the presence of bacterial and parasitic pathogens. Treatment will be offered to all infected participants and the clinical treatment response will be recorded. Data obtained will be utilised to develop patient-centred clinical algorithms that will be validated in primary health care centres in the four study countries in subsequent studies. DISCUSSION: Our research will deepen the understanding of the importance of persistent diarrhoea and related digestive disorders in the tropics. A diversity of intestinal pathogens will be assessed for potential associations with persistent diarrhoea and persistent abdominal pain. Different diagnostic methods will be compared, clinical symptoms investigated and diagnosis treatment algorithms developed for validation in selected primary health care centres. The findings from this study will improve differential diagnosis and evidence-based clinical management of digestive syndromes in the tropics. TRIAL REGISTRATION: ClinicalTrials.gov; identifier: NCT02105714 . PMID- 26282540 TI - Structural basis for quinine-dependent antibody binding to platelet integrin alphaIIbbeta3. AB - Drug-induced immune thrombocytopenia (DITP) is caused by antibodies that react with specific platelet-membrane glycoproteins when the provoking drug is present. More than 100 drugs have been implicated as triggers for this condition, quinine being one of the most common. The cause of DITP in most cases appears to be a drug-induced antibody that binds to a platelet membrane glycoprotein only when the drug is present. How a soluble drug promotes binding of an otherwise nonreactive immunoglobulin to its target, leading to platelet destruction, is uncertain, in part because of the difficulties of working with polyclonal human antibodies usually available only in small quantities. Recently, quinine dependent murine monoclonal antibodies were developed that recognize a defined epitope on the beta-propeller domain of the platelet integrin alphaIIb subunit (GPIIb) only when the drug is present and closely mimic the behavior of antibodies found in human patients with quinine-induced thrombocytopenia in vitro and in vivo. Here, we demonstrate specific, high-affinity binding of quinine to the complementarity-determining regions (CDRs) of these antibodies and define in crystal structures the changes induced in the CDR by this interaction. Because no detectable binding of quinine to the target integrin could be demonstrated in previous studies, the findings indicate that a hybrid paratope consisting of quinine and reconfigured antibody CDR plays a critical role in recognition of its target epitope by an antibody and suggest that, in this type of drug-induced immunologic injury, the primary reaction involves binding of the drug to antibody CDRs, causing it to acquire specificity for a site on a platelet integrin. PMID- 26282542 TI - Retraction note to: the plateau in mnemonic resolution across large set sizes indicates discrete resource limits in visual working memory. PMID- 26282541 TI - Fibrin activates GPVI in human and mouse platelets. AB - The glycoprotein VI (GPVI)-Fc receptor gamma (FcRgamma) chain is the major platelet signaling receptor for collagen. Paradoxically, in a FeCl3 injury model, occlusion, but not initiation of thrombus formation, is delayed in GPVI-deficient and GPVI-depleted mice. In this study, we demonstrate that GPVI is a receptor for fibrin and speculate that this contributes to development of an occlusive thrombus. We observed a marked increase in tyrosine phosphorylation, including the FcRgamma chain and Syk, in human and mouse platelets induced by thrombin in the presence of fibrinogen and the alphaIIbbeta3 blocker eptifibatide. This was not seen in platelets stimulated by a protease activated receptor (PAR)-4 peptide, which is unable to generate fibrin from fibrinogen. The pattern of tyrosine phosphorylation was similar to that induced by activation of GPVI. Consistent with this, thrombin did not induce tyrosine phosphorylation of Syk and the FcRgamma chain in GPVI-deficient mouse platelets. Mouse platelets underwent full spreading on fibrin but not fibrinogen, which was blocked in the presence of a Src kinase inhibitor or in the absence of GPVI. Spreading on fibrin was associated with phosphatidylserine exposure (procoagulant activity), and this too was blocked in GPVI-deficient platelets. The ectodomain of GPVI was shown to bind to immobilized monomeric and polymerized fibrin. A marked increase in embolization was seen following FeCl3 injury in GPVI-deficient mice, likely contributing to the delay in occlusion in this model. These results demonstrate that GPVI is a receptor for fibrin and provide evidence that this interaction contributes to thrombus growth and stability. PMID- 26282543 TI - Steroidogenesis in plants--Biosynthesis and conversions of progesterone and other pregnane derivatives. AB - In plants androstanes, estranes, pregnanes and corticoids have been described. Sometimes 17beta-estradiol, androsterone, testosterone or progesterone were summarized as sex hormones. These steroids influence plant development: cell divisions, root and shoot growth, embryo growth, flowering, pollen tube growth and callus proliferation. First reports on the effect of applicated substances and of their endogenous occurrence date from the early twenties of the last century. This caused later on doubts on the identity of the compounds. Best investigated is the effect of progesterone. Main steps of the progesterone biosynthetic pathway have been analyzed in Digitalis. Cholesterol-side-chain cleavage, pregnenolone and progesterone formation as well as the stereospecific reduction of progesterone are described and the corresponding enzymes are presented. Biosynthesis of androstanes, estranes and corticoids is discussed. Possible progesterone receptors and physiological reactions on progesterone application are reviewed. PMID- 26282545 TI - Immune Checkpoint Inhibitors for Cancer Therapy: Clinical Efficacy and Safety. AB - A major breakthrough in cancer immunotherapy was the discovery of immune checkpoint proteins, which function to effectively inhibit the immune system through various mechanisms. The first of such molecules shown to inhibit both T cell proliferation and IL-2 production was cytotoxic T-lymphocyte associated protein 4 (CTLA-4). With this discovery, efforts turned to blocking this inhibitory pathway in an attempt to activate dormant T-cells directed at cancer cells. The first antibody directed against CTLA-4, ipilimumab, was quickly ushered into clinical trials and was approved by the US Food and Drug Administration (FDA) for the treatment of metastatic melanoma in 2011. Following the success of ipilimumab, other immune checkpoints were studied as possible targets for inhibition. One such interaction was that of the programmed cell death-1 (PD-1) T-cell receptor and its ligand found on many cancer cells, programmed death-ligand 1 (PD-L1). Unfortunately, the untoward effects of blocking the immune system's natural inhibitory mechanisms have manifested clinically as diarrhea, rash, and hepatitis. Nevertheless, the exciting field of immune checkpoint inhibitors offers a potential curative option for many cancer patients who previously had a more dismal prognosis. The authors aim to provide a comprehensive review of the literature and update on the use of CTLA-4, PD-1 and PD-L1 targeted therapy in the treatment of cancer and other molecules still in the early development phase. PMID- 26282546 TI - Emerging Drug Target In Pancreatic Cancer: Placing Sirtuin 1 on the Canvas. AB - Sirtuin 1 is a protein deacetylase that regulates a large number of proteins often functionally implicated in tumor development and progression. Its pleiotropic function has turned SIRT1 into an attractive chemotherapeutic target, underscored by very promising preclinical results with SIRT1 inhibitors in the treatment of chronic myeloid leukemia. Here, we revisit the studies on SIRT1 as an emerging target for therapy in pancreatic cancer, a tumor with dismal outcomes for which currently few therapeutic options are available. We highlight those potential SIRT1 target genes that are commonly affected in pancreatic cancer according to recent genomic analyses. PMID- 26282547 TI - Extracellular Ca(2+) Selectively Enhances Adriamycin-induced Cell Death in Human Hepatoma Cells. AB - It has been shown that the regulatory mechanisms of Ca(2+) signaling between tumor and normal cells are different, providing new insight into the pharmacological modulation of anticancer drugs. However, it remains unclear whether there is any difference between hepatoma and normal hepatic cells in their response to extracellular Ca(2+) ([Ca(2+)]e). In the present study, the growth inhibition, apoptosis and necrosis rates of human normal embryo hepatic L02 and human hepatoma HepG2 cells exposed to additional calcium ([Ca(2+)]a)and adriamycin (ADM), a chemotherapeutic agent to treat hepatocellular carcinoma, were measured by MTT and annexin V/PI assays, respectively. The results showed that the growth inhibition, necrosis and apoptosis rates, as well as intracellular Ca(2+) concentrations ([Ca(2+)]i) induced by [Ca(2+)]e in HepG2 cells were higher than those in L02 cells. Moreover, [Ca(2+)]e was able to selectively enhance ADM-induced growth inhibition, apoptosis and necrosis in HepG2 cells, but not in L02 cells. ADM and [Ca(2+)]a co-treatment had a significant interaction effect to increase [Ca(2+)]i in both cell lines, although there was no significant difference in [Ca(2+)]i between the two cells. To further elucidate the mechanisms involved in the selective promotion of [Ca(2+)]e in HepG2 and L02 cells, the levels of these apoptosis regulatory proteins (bcl-2, bax and procaspase-3) and the caspase-3 activity following treatment of HepG2 and L02 cells with ADM or/and [Ca(2+)]a were investigated. The results showed that treating HepG2 cells with [Ca(2+)]a and ADM increased the level of bax protein and caspase-3 activity while decreasing the level of bcl-2 protein, compared with treatment with ADM alone. However, no significant change was noted in L02 cells. These results indicate that hepatoma HepG2 cells are more sensitive to [Ca2+]e than normal hepatic L02 cells and that [Ca(2+)]a can selectively enhance ADM induced cell death in HepG2 cells. The mechanism of this intensive pro-apoptotic effect can be ascribed to up-regulation of bax and the simultaneous down regulation of bcl-2, followed by the switch from procaspase-3 to caspase-3, which executed apoptosis. The present data suggest the potency of the calcium ion as an enhancer of ADM. PMID- 26282548 TI - A New Strategy to Target Acute Myeloid Leukemia Stem and Progenitor Cells Using Chidamide, a Histone Deacetylase Inhibitor. AB - Leukemia stem cells (LSCs) are responsible for treatment failure and relapse in acute myeloid leukemia (AML). Therefore, development of novel LSCs-targeting therapeutic strategies is of crucial clinical importance to improve the treatment outcomes of AML. Histone deacetylase (HDAC) inhibitors have shown potent and specific anticancer stem cell activities in preclinical studies. Chidamide, a novel benzamide-type selectively HDAC inhibitor, has been reported to induce G1 arrest and apoptosis in the relatively mature progenitor population, whereas its effect on primitive LSCs has not been clarified. In this study, we demonstrated that chidamide specifically induces apoptosis in LSC-like cells and primary AML CD34(+) cells in a concentration- and time-dependent manner. Our further molecular mechanistic study uncovered that chidamide induces LSCs death by activation of reactive oxygen species (ROS). It compromises the mitochondria membrane potential, modulates antiapoptotic and pro-apoptotic proteins in BCL2 family and activates caspase-3 leading to PARP degradation. Meanwhile, chidamide activates CD40 and modulates its downstream signaling pathways, JNK and NFkappaB. The results of this study suggest that chidamide may be a novel LSC-targeting agent for AML therapeutics. PMID- 26282549 TI - The Prognosis of Patients with Liver Metastases from Colorectal Cancer still Depends on Anatomical Presentation more than on Treatments. AB - BACKGROUND: The best management of liver metastases from colorectal cancer is still debated and little is known about the true impact of treatments on survival. MATERIALS AND METHODS: The study involved 122 patients (77 males), aged 64.0 +/- 11.0 years (range: 27.8-86.1) at diagnosis of liver metastatization (synchronous in 59). All underwent chemotherapy and at least one procedure of radiofrequency ablation; 53 also had partial hepatic resections. Demographics, tumor characteristics and survival outcomes from liver metastatization were analyzed with univariate and multivariate techniques. This analysis was performed also taking into account relative survival as the best estimate of specific survival. RESULTS: The analysis with observed survival selected the categorized number of involved lymph nodes in the colorectal specimens as the only statistically significant predictor, while the analysis with relative survival also showed site of the primary tumor (above the sigmoid colon or otherwise) and number of liver metastases as significant factors. The standardized mortality ratio was 9.673 (95% CI: 7.668-11.663) and a total of 201.85 years of life were lost in comparison with the survival of the reference population. CONCLUSIONS: The computation of relative survival - better than observed survival - selected a more adequate number of predictors, making investigation of even limited series of patients with confounding factors reliable. The finding that prognosis was mainly dependent on the anatomical presentation of the primary tumor and of liver metastases - instead of treatments - could explain the still contrasting opinions on the role of the available therapies in this field. PMID- 26282550 TI - Thinking outside the boxes: Using current reading models to assess and treat developmental surface dyslexia. AB - Improving the reading performance of children with developmental surface dyslexia has proved challenging, with limited generalisation of reading skills typically reported after intervention. The aim of this study was to provide tailored, theoretically motivated intervention to two children with developmental surface dyslexia. Our objectives were to improve their reading performance, and to evaluate the utility of current reading models in therapeutic practice. Detailed reading and cognitive profiles for two male children with developmental surface dyslexia were compared to the results obtained by age-matched control groups. The specific area of single-word reading difficulty for each child was identified within the dual route model (DRM) of reading, following which a theoretically motivated intervention programme was devised. Both children showed significant improvements in single-word reading ability after training, with generalisation effects observed for untrained words. However, the assessment and intervention results also differed for each child, reinforcing the view that the causes and consequences of developmental dyslexia, even within subtypes, are not homogeneous. Overall, the results of the interventions corresponded more closely with the DRM than other current reading models, in that real word reading improved in the absence of enhanced nonword reading for both children. PMID- 26282551 TI - Results of an online questionnaire to survey calf management practices on dairy cattle breeding farms in Austria and to estimate differences in disease incidences depending on farm structure and management practices. AB - BACKGROUND: Calf disease may result in great economic losses. To implement prevention strategies it is important to gain information on management and to point out risk factors. The objective of this internet based survey was to describe calf management practices on registered dairy breeding farms in Austria and to estimate differences in calf disease incidences depending on farm structure and management practices. RESULTS: A total of 1287 questionnaires were finally analysed (response rate 12.2 %). Herd characteristics and regional distribution of farms indicated that this survey gives a good overview on calf management practices on registered dairy farms in Austria. The median number of cows per farm was 20 (interquartile range 13-30). Significant differences regarding farm characteristics and calf management between small and large farms (<=20 vs >20 cows) were present. Only 2.8 % of farmers tested first colostrum quality by use of a hydrometer. Storing frozen colostrum was more prevalent on large farms (80.8 vs 64.2 %). On 85.1 % of the farms, whole milk, including waste milk, was fed to the calves. Milk replacer and waste milk were more often used on large farms. In accordance with similar studies from other countries, calf diarrhoea was indicated as the most prevalent disease. Multivariable logistic regression analysis revealed that herd size was associated with calf diarrhoea and calf respiratory tract disease, with higher risk of disease on large farms. Furthermore, feeding waste milk to the calves was associated with increasing calf diarrhoea incidence on farm. In the final model with calf respiratory tract disease as outcome, respondents from organic farms reported less often a respiratory tract disease incidence of over 10 % compared with conventional farms [odds ratio (OR) 0.40, 95 % confidence interval (CI) 0.21-0.75] and farmers that housed calves individually or in groups after birth significantly reported more often to have an incidence of respiratory tract disease >10 % compared with farms where all calves were housed individually (OR 2.28, 95 % CI 1.16-4.48). CONCLUSION: The results obtained in this study provide an overview on calf management on dairy breeding farms in Austria and may help to further point out areas to be improved on farm. PMID- 26282552 TI - Graphene-based hybrid films for plasmonic sensing. AB - Graphene, a one-atomic-layer-thick planar sheet of sp(2)-bonded carbon configured in a two-dimensional hexagonal lattice, has attracted considerable research interest with regard to sensing-related applications owing to its extraordinary electronic, optical, chemical, and mechanical properties. Graphene plasmonics may be excited in the mid-infrared-to-terahertz regions with high spatial confinement, low loss, and excellent tunability. Meanwhile, graphene can be utilized to tune the plasmonic properties of conventional metallic nanostructures in the visible and near-infrared regions, allowing it to act as a versatile component in various plasmonic applications. This article reviews the recent progress in graphene-based hybrid films used for plasmonic sensing and detection. We particularly emphasize on the unique roles and advantages of graphene in surface-enhanced Raman scattering (SERS) for bare graphene or graphene-metal hybrid films, and plasmonic refractive index (RI) sensing for graphene-metal or graphene-insulator hybrids, among other plasmonic sensing applications. The preparation of graphene-based hybrid films, their functionalization and signal detection techniques are also reviewed. Finally, the perspectives and current challenges in the use of graphene-based hybrid films for plasmonic sensing are outlined. PMID- 26282553 TI - Sample size calculation for a stepped wedge trial. AB - BACKGROUND: Stepped wedge trials (SWTs) can be considered as a variant of a clustered randomised trial, although in many ways they embed additional complications from the point of view of statistical design and analysis. While the literature is rich for standard parallel or clustered randomised clinical trials (CRTs), it is much less so for SWTs. The specific features of SWTs need to be addressed properly in the sample size calculations to ensure valid estimates of the intervention effect. METHODS: We critically review the available literature on analytical methods to perform sample size and power calculations in a SWT. In particular, we highlight the specific assumptions underlying currently used methods and comment on their validity and potential for extensions. Finally, we propose the use of simulation-based methods to overcome some of the limitations of analytical formulae. We performed a simulation exercise in which we compared simulation-based sample size computations with analytical methods and assessed the impact of varying the basic parameters to the resulting sample size/power, in the case of continuous and binary outcomes and assuming both cross sectional data and the closed cohort design. RESULTS: We compared the sample size requirements for a SWT in comparison to CRTs based on comparable number of measurements in each cluster. In line with the existing literature, we found that when the level of correlation within the clusters is relatively high (for example, greater than 0.1), the SWT requires a smaller number of clusters. For low values of the intracluster correlation, the two designs produce more similar requirements in terms of total number of clusters. We validated our simulation based approach and compared the results of sample size calculations to analytical methods; the simulation-based procedures perform well, producing results that are extremely similar to the analytical methods. We found that usually the SWT is relatively insensitive to variations in the intracluster correlation, and that failure to account for a potential time effect will artificially and grossly overestimate the power of a study. CONCLUSIONS: We provide a framework for handling the sample size and power calculations of a SWT and suggest that simulation-based procedures may be more effective, especially in dealing with the specific features of the study at hand. In selected situations and depending on the level of intracluster correlation and the cluster size, SWTs may be more efficient than comparable CRTs. However, the decision about the design to be implemented will be based on a wide range of considerations, including the cost associated with the number of clusters, number of measurements and the trial duration. PMID- 26282554 TI - Public response to the 2014 chemical spill in West Virginia: knowledge, opinions and behaviours. AB - BACKGROUND: On January 9(th) 2014, a faulty storage tank leaked 10,000 gal of an industrial coal processing liquid into the Elk River in West Virginia (WV), contaminating the drinking water of the nine counties collectively known as the Kanawha Valley. The aim of this study was to 1) explore how and when people obtained information about the water contamination and 2) understand how individual and social factors such as socio-demographic characteristics, timing of information, trust in government, and risk perception influenced compliance with recommended behaviours and the public's views on the need for environmental regulations. METHODS: Between February 7-26, 2014, a survey was conducted of adult residents of West Virginia including geographic areas affected and non affected by the chemical spill. The total population-based sample size was 690 and the survey was administered online. Descriptive statistics and multivariate statistical models were created to determine what factors influenced compliance and public opinions. RESULTS: Findings from this study show that, during the 2014 West Virginia water crisis, information about water contamination spread quickly, as 73 % of survey respondents across the state and 89 % within the affected counties reported they heard about the incident the same day it occurred. Most people received the information promptly, understood what happened, and understood what to do to prevent exposure to the contaminant. The majority of respondents living in affected counties (70 %) followed the recommended behaviours. Among participants who voiced an opinion on the role of government in environmental regulations, the majority of respondents (54 %) reported there is "too little regulation." CONCLUSION: Data from this study show that a higher perception of risk and timely receipt of information are associated with compliance with recommended behaviours, underlying the importance of releasing information to the public as quickly as possible during a crisis. This study also highlights the importance of coordinating risk communication activities beyond the area of the incident to assure public understanding of what measures are recommended, which are not and where. PMID- 26282555 TI - Development of evaporative light scattering detector for capillary electrochromatography and capillary liquid chromatography. AB - The paper describes a microfluidic evaporative light scattering detector (MUELSD) for capillary electrochromatography and capillary liquid chromatography. The detector, consisting of a microfluidic nebulizer, a miniaturized evaporative module, a sheath gas module, and a light scattering chamber, was developed and optimized. Carrier gas exits from an extremely narrow circular gap (about 5 MUm) between the spraying capillary o.d. and the nozzle i.d., impacting on the mobile phase liquid with supersonic velocity, to nebulize the effluent of a few hundred nL/min from the capillary outlet. The evaporation process was found to be accomplished at ambient temperature. A sheath gas module featuring a structural necking subsequent to drift tube endings was found to enhance the reproducibility and increase the S/N. Excellent linearity of the optimal MUELSD was 3 orders of magnitude (0.2-40 ng; R(2) = 0.9998). The limit of detection (LOD) for glucose with a capillary column was 100 pg. Finally, the MUELSD coupled to pressurized capillary eletrochromatography (pCEC) was applied to the analysis of six active components in traditional Chinese medicine extract, demonstrating the feasibility of the detector for capillary liquid separation system. PMID- 26282556 TI - Florfenicol induces early embryonic death in eggs collected from treated hens. AB - BACKGROUND: Florfenicol, a commonly used veterinary antibiotic, was reported to have caused a severe drop in egg hatchability following its off-label use on a broiler breeder farm in South Africa. According to the pharmacovigilance report, hatchability dropped by 80 % for up to a week following a five day course at 10 mg/kg (both males and females treated metaphylactically) to manage an Escherichia coli infection. While mammalian toxicity studies indicate the potential for early embryonic death in utero or testicular damage, no literature is available on the avian toxicity of florfenicol. For this study we investigated the effects of florfenicol at various doses from 10 to 90 mg/kg on the egg hatchability in a breeder flock we kept and established under controlled conditions, with the same cockerels and hens being exposed in a phased manner. RESULTS: Following five days of oral exposure, no toxic signs were evident in any of the cockerels or hens treated at doses up to 90 mg/kg. Treatment of only the cockerels had no effect on egg hatchability, while treatment of only the hens at doses of 60 and 90 mg/kg resulted in decreased hatchability of 0 % in comparison to 70 % of the control as early 24 h after treatment. In all cases, decreased hatchability was associated with embryonic death at 5 days of development. The toxic effects of florfenicol were completely reversible with comparable hatchability being present by day 4 post-treatment withdrawal. Toxicity correlated with total egg florfenicol concentrations with an LC50 of 1.07 MUg/g. CONCLUSION: Florfenicol appears to be toxic to the developing chick embryo at around day 5 of incubation, in the absence of related toxicity in the hen or cockerel. PMID- 26282558 TI - Successful multiple-step management of intravenous leiomyomatosis diagnosed after episode of acute abdominal pain: Case report and review of literature. AB - INTRODUCTION: We present the case of a 37-year old woman diagnosed with intravenous leiomyomatosis (IVL) that was managed uneventfully with multiple-step management. PRESENTATION OF CASE: A 37-year-old woman was admitted because of acute abdominal pain. Emergency Computed Tomography demonstrated a big pelvic mass 5*15cm of heterogenous composition intaking the contrast agent. Total hysterectomy with salpingoophorectomy was proposed to patient, however, patient expressed her will for fertility preservation and gave consent only for the resection of a single ovary. Laparotomy revealed the presence of myoma, multiple lesions of potential adenomyosis and cordon-shaped formations arising from uterus and extending mainly to left ovary. Final histological diagnosis was intravenous leiomyomatosis (IVL). MRI angiography revealed the presence of residual lesions in inferior vena cava. Laparoscopic resection was performed one month after laparotomy and left ovary was resected without complications. Venovenous bypass was finally performed three months later from initial surgery. The process was significantly labored, resulted in the successful resection of intravenous lesions but was complicated intraoperatively by right kidney rupture. After a follow-up of 33 months, case remains uncomplicated without signs or symptoms of potential recurrence. DISCUSSION: Intravenous leiomyomatosis represents a rare clinical entity histologically bening but clinically aggressive. No consensus exists regarding the optimal management, especially in cases with initial will for fertility preservation. CONCLUSION: IVL represents a rare clinical entity often presenting difficulties in diagnosis and optimal treatment. Large case series studies should be encouraged to assess the optimal management. PMID- 26282559 TI - A case report of duplex gallbladder and review of the literature. AB - Gallbladder duplication is a rare congenital abnormality first described by Boyden in 1926. Pre-operative diagnosis is essential in identifying anatomical abnormalities in order to avoid biliary injuries at the time of surgery or performance of an incomplete operation. We present a case of a duplex gallbladder and review of the literature. PMID- 26282557 TI - Accuracy of imputation using the most common sires as reference population in layer chickens. AB - BACKGROUND: Genotype imputation has become a standard practice in modern genetic research to increase genome coverage and improve the accuracy of genomic selection (GS) and genome-wide association studies (GWAS). We assessed accuracies of imputing 60K genotype data from lower density single nucleotide polymorphism (SNP) panels using a small set of the most common sires in a population of 2140 white layer chickens. Several factors affecting imputation accuracy were investigated, including the size of the reference population, the level of the relationship between the reference and validation populations, and minor allele frequency (MAF) of the SNP being imputed. RESULTS: The accuracy of imputation was assessed with different scenarios using 22 and 62 carefully selected reference animals (Ref(22) and Ref(62)). Animal-specific imputation accuracy corrected for gene content was moderate on average (~ 0.80) in most scenarios and low in the 3K to 60K scenario. Maximum average accuracies were 0.90 and 0.93 for the most favourable scenario for Ref(22) and Ref(62) respectively, when SNPs were masked independent of their MAF. SNPs with low MAF were more difficult to impute, and the larger reference population considerably improved the imputation accuracy for these rare SNPs. When Ref(22) was used for imputation, the average imputation accuracy decreased by 0.04 when validation population was two instead of one generation away from the reference and increased again by 0.05 when validation was three generations away. Selecting the reference animals from the most common sires, compared with random animals from the population, considerably improved imputation accuracy for low MAF SNPs, but gave only limited improvement for other MAF classes. The allelic R(2) measure from Beagle software was found to be a good predictor of imputation reliability (correlation ~ 0.8) when the density of validation panel was very low (3K) and the MAF of the SNP and the size of the reference population were not extremely small. CONCLUSIONS: Even with a very small number of animals in the reference population, reasonable accuracy of imputation can be achieved. Selecting a set of the most common sires, rather than selecting random animals for the reference population, improves the imputation accuracy of rare alleles, which may be a benefit when imputing with whole genome re-sequencing data. PMID- 26282560 TI - alpha-linolenic acid and docosahexaenoic acid, alone and combined with trastuzumab, reduce HER2-overexpressing breast cancer cell growth but differentially regulate HER2 signaling pathways. AB - BACKGROUND: Diets rich in the n-3 fatty acid alpha-linolenic acid (ALA) have been shown to reduce breast tumor growth, enhance the effectiveness of the HER2 targeted drug trastuzumab (TRAS) and reduce HER2 signaling in mouse models. It is unclear whether this is due to direct effects of ALA or due to its long-chain n-3 fatty acids metabolites including docosahexaenoic acid (DHA). METHODS: The ability of HER2-overexpressing BT-474 human breast cancer cells to convert ALA to long-chain n-3 fatty acids was determined by measurement of phospholipid fatty acids by gas chromatography following treatment with 100 MUM ALA. The effects of 96 h treatment with ALA or DHA, at serum levels seen in mice (50-100 MUM), alone and combined with TRAS (10 MUg/ml), on BT-474 cell growth measured by trypan blue exclusion, apoptosis measured by flow cytometric analysis of Annexin-V/7-AAD stained cells (ALA and TRAS treatment only) and protein biomarkers HER2 signaling measured by western blot were determined. RESULTS: ALA-treated BT-474 cells had higher phospholipid ALA but no increase in downstream n-3 metabolites including DHA. Both ALA and DHA reduced cell growth with and without TRAS. ALA had no effect on apoptosis. ALA and DHA showed opposite effects on Akt and MAPK phosphorylation; ALA increased and DHA decreased phosphorylation. CONCLUSIONS: Together these data suggest that, while both ALA and its DHA metabolite can reduce HER2-overexpressing breast cancer growth with and without TRAS, they demonstrate for the first time that DHA is responsible for the effects of ALA rich diets on HER2 signaling pathways. PMID- 26282562 TI - Expression of feruloyl esterase A from Aspergillus terreus and its application in biomass degradation. AB - Feruloyl esterases (FAEs) are key enzymes involved in the complete biodegradation of lignocelluloses, which could hydrolyze the ester bonds between hemicellulose and lignin. The coding sequence of a feruloyl esterase A (AtFaeA) was cloned from Aspergillus terreus and the recombinant AtFaeA was constitutively expressed in Pichia pastoris. The SDS-PAGE analysis of purified AtFaeA showed two protein bands owing to the different extent of glycosylation, and the recombinant AtFaeA had an optimum temperature of 50 degrees C and an optimum pH of 5.0. The substrate utilization and primary sequence identity of AtFaeA demonstrated that it is a type-A feruloyl esterase. The hydrolysis of corn stalk and corncob by xylanase from Aspergillus niger could be significantly improved in concert with recombinant AfFaeA. PMID- 26282561 TI - Outcome Reporting in Cardiac Surgery Trials: Systematic Review and Critical Appraisal. AB - BACKGROUND: There is currently no accepted standard for reporting outcomes following cardiac surgery. The objective of this paper was to systematically review the literature to evaluate the current use and definition of perioperative outcomes reported in cardiac surgery trials. METHODS AND RESULTS: We reviewed 5 prominent medical and surgical journals on Medline from January 1, 2010, to June 30, 2014, for randomized controlled trials involving coronary artery bypass grafting and/or valve surgery. We identified 34 trials meeting inclusion criteria. Sample sizes ranged from 57 to 4752 participants (median 351). Composite end points were used as a primary outcome in 56% (n=19) of the randomized controlled trials and as a secondary outcome in 12% (n=4). There were 14 different composite end points. Mortality at any time (all-cause and/or cardiovascular) was reported as an individual end point or as part of a combined end point in 82% (n=28), myocardial infarction was reported in 68% (n=23), and bleeding was reported in 24% (n=8). Patient-centered outcomes, such as quality of life and functional classification, were reported in 29% (n=10). Definition of clinical events such as myocardial infarction, stroke, renal failure, and bleeding varied considerably among trials, particularly for postoperative myocardial infarction and bleeding, for which 8 different definitions were used for each. CONCLUSIONS: Outcome reporting in the cardiac surgery literature is heterogeneous, and efforts should be made to standardize the outcomes reported and the definitions used to ascertain them. The development of standardizing outcome reporting is an essential step toward strengthening the process of evidence-based care in cardiac surgery. PMID- 26282563 TI - Small-Area Estimation of Spatial Access to Care and Its Implications for Policy. AB - Local or small-area estimates to capture emerging trends across large geographic regions are critical in identifying and addressing community-level health interventions. However, they are often unavailable due to lack of analytic capabilities in compiling and integrating extensive datasets and complementing them with the knowledge about variations in state-level health policies. This study introduces a modeling approach for small-area estimation of spatial access to pediatric primary care that is data "rich" and mathematically rigorous, integrating data and health policy in a systematic way. We illustrate the sensitivity of the model to policy decision making across large geographic regions by performing a systematic comparison of the estimates at the census tract and county levels for Georgia and California. Our results show the proposed approach is able to overcome limitations of other existing models by capturing patient and provider preferences and by incorporating possible changes in health policies. The primary finding is systematic underestimation of spatial access, and inaccurate estimates of disparities across population and across geography at the county level with respect to those at the census tract level with implications on where to focus and which type of interventions to consider. PMID- 26282564 TI - The Trauma Response Team: a Community Intervention for Gang Violence. AB - While violent crime has decreased in many cities in the USA, gang-related violence remains a serious problem in impoverished inner city neighborhoods. In Syracuse, New York, gang-related murders and gun shots have topped other New York state cities. Residents of the high-murder neighborhoods suffer trauma similar to those living in civil conflict zones. The Trauma Response Team was established in 2010, in collaboration with the Police Department, health care institutions, and emergency response teams and with the research support of Syracuse University faculty. Since its inception, gang-related homicides and gun shots have decreased in the most severely affected census tracts. PMID- 26282565 TI - Accuracy of Cone-beam Computed Tomography in the Detection of a Second Mesiobuccal Root Canal in Endodontically Treated Teeth: An Ex Vivo Study. AB - INTRODUCTION: There is a high incidence of a second mesiobuccal root canal (MB2) in maxillary molars. The study aim is to assess the accuracy of cone-beam computed tomographic (CBCT) imaging in detecting a second mesiobuccal root canal in endodontically treated maxillary molars. METHODS: The study sample consisted of 60 extracted maxillary molars, which were endodontically opened and examined under a dental operating microscope for the presence of an MB2. The teeth were then further examined using micro-computed tomographic imaging as the gold standard. Root canals were filled (except the MB2) and were then subdivided into an experimental and a control group. After fixing the teeth in a dry human skull, they were scanned using CBCT imaging (AccuiTomo 170; Morita Inc, Tarumi-cho Suita City, Osaka, Japan). The observers for this study were 2 experienced radiologists blinded to the group allocation of controls and experiments; they evaluated the images twice independently. Sensitivity, specificity, and accuracy were calculated as well as the kappa values for both inter- and intraobserver agreement. RESULTS: From 30 teeth, which were diagnosed without an MB2 under examination with a dental operating microscope, 6 teeth proved to have an MB2 using MUCT (20%). Intraobserver reliability was high for both observers 1 (R = 0.85) and 2 (R = 0.96). Interobserver reliability as assessed by the Cohen kappa was excellent (R = 0.89). CBCT sensitivity for detecting an MB2 was 96%, specificity was 100%, and total accuracy was 98%. CONCLUSIONS: CBCT imaging is a suitable diagnostic technique for detecting a missed MB2 in endodontically treated teeth. PMID- 26282566 TI - Improvement of depth dose distribution using multiple-field irradiation in boron neutron capture therapy. AB - It is important that improvements are made to depth dose distribution in boron neutron capture therapy, because the neutrons do not reach the innermost regions of the human body. Here, we evaluated the dose distribution obtained using multiple-field irradiation in simulation. From a dose volume histogram analysis, it was found that the mean and minimum tumor doses were increased using two-field irradiation, because of improved dose distribution for deeper-sited tumors. PMID- 26282567 TI - Evaluation of TK1 targeting carboranyl thymidine analogs as potential delivery agents for neutron capture therapy of brain tumors. AB - In this report we describe studies with N5-2OH, a carboranyl thymidine analog (CTA), which is a substrate for thymidine kinase 1 (TK1), using the F98 rat glioma model. In vivo BNCT studies have demonstrated that intracerebral (i.c.) osmotic pump infusion of N5-2OH yielded survival data equivalent to those obtained with i.v. administration of boronophenylalanine (BPA). The combination of N5-2OH and BPA resulted in a modest increase in MST of F98 glioma bearing rats compared to a statistically significant increase with the RG2 glioma model, as has been previously reported by us (Barth et al., 2008). This had lead us to synthesize a second generation of CTAs that have improved in vitro enzyme kinetics and in vivo tumor uptake (Agarwal et al., 2015). PMID- 26282568 TI - Fatal carotid blowout syndrome after BNCT for head and neck cancers. AB - Boron neutron capture therapy (BNCT) is high linear energy transfer (LET) radiation and tumor-selective radiation that does not cause serious damage to the surrounding normal tissues. BNCT might be effective and safe in patients with inoperable, locally advanced head and neck cancers, even those that recur at previously irradiated sites. However, carotid blowout syndrome (CBS) is a lethal complication resulting from malignant invasion of the carotid artery (CA); thus, the risk of CBS should be carefully assessed in patients with risk factors for CBS after BNCT. Thirty-three patients in our institution who underwent BNCT were analyzed. Two patients developed CBS and experienced widespread skin invasion and recurrence close to the carotid artery after irradiation. Careful attention should be paid to the occurrence of CBS if the tumor is located adjacent to the carotid artery. The presence of skin invasion from recurrent lesions after irradiation is an ominous sign of CBS onset and lethal consequences. PMID- 26282569 TI - Individual patient data meta-analysis of antiplatelet regimens after noncardioembolic stroke or TIA: rationale and design. AB - BACKGROUND: The Cerebrovascular Antiplatelet Trialists' Collaborative Group was formed to obtain and analyze individual patient data from the major randomized trials of common antiplatelet regimens after cerebral ischemia. Although the risk of stroke can be reduced by antiplatelet drugs, there continues to be uncertainty about the balance of risk and benefits of different antiplatelet regimens for an individual patient. AIMS: Our aim is to provide clinicians with a thorough evidence-based answer on these therapeutic alternatives. METHODS: We have identified six large randomized trials and plan to meta-analyze the data on an individual patient level. In total, these trials have enrolled 46 948 patients with cerebral ischemia. Uniquely, the Cerebrovascular Antiplatelet Trialists' Collaborative Group has secured access to the individual data of all of these trials, with the participation of key investigators and pharmaceutical companies. Our principal objective includes deriving a reliable estimate of the efficacy of different antiplatelet regimens on key outcomes including serious vascular events, major ischemic events, major bleeding, and intracranial hemorrhage. RESULTS: We propose to redefine composite outcome events, if necessary, to achieve comparability. Further, we aim to build and validate prognostic models for the risk of major bleeding and intracranial hemorrhage and to build a decision model that may support evidence-based decision making about which antiplatelet regimen would be most effective in different risk groups of patients. CONCLUSIONS: This paper outlines inclusion criteria, outcome measures, baseline characteristics, and planned statistical analysis. PMID- 26282570 TI - Feasibility of the Factorial Survey Method in Aging Research: Consistency Effects Among Older Respondents. AB - BACKGROUND: The factorial survey (FS) method is increasingly used in the social sciences. It is particularly suitable for studying decision situations that are difficult to assess empirically. This article evaluates whether the FS method is suitable for studying decisions in gerontological research. METHODS: The present article draws on data from the Housing Opportunities & Mobility in the Elderly study. A total of 103 respondents (between 55 and 90 years) were asked to make hypothetical relocation decisions. The consistency of these responses was assessed as a function of respondents' age, gender, immigration background, education, household income, employment status, and intention to move. RESULTS: No significant differences in response consistency were attributable to age, gender, education, or immigration background. The personal relevance of the survey topic was positively related to response consistency in multiperson households. CONCLUSION: FS method can, under certain methodological conditions, be used among older adults especially when the topic of the survey is relevant to their daily lives. PMID- 26282571 TI - Honor Thy Parents: An Ethnic Multigroup Analysis of Filial Responsibility, Health Perceptions, and Caregiving Decisions. AB - The present study explores patterns of parity and disparity in the effect of filial responsibility on health-related evaluations and caregiving decisions. Participants who identified as White, Black, Hispanic, or Asian/Pacific Islander read a vignette about an older man needing medical care. They were asked to imagine that they were the man's son and answer questions regarding their likelihood of hiring a health care advocate (HCA) for services related to the father's care. A multigroup (ethnicity) path analysis was performed, and an intercept invariant multigroup model fits the data best. Direct and indirect effect estimation showed that filial responsibility mediated the relationship between both the perceived severity of the father's medical condition and the perceived need for medical assistance and the likelihood of hiring an HCA only for White and Hispanic participants, albeit differently. The findings demonstrate that culture and ethnicity affect health evaluations and caregiving decision making. PMID- 26282572 TI - Palladium-Catalyzed Desulfitative Oxidative Coupling between Arenesulfinic Acid Salts and Allylic Alcohols: A Strategy for the Selective Construction of beta Aryl Ketones and Aldehydes. AB - An efficient palladium-catalyzed desulfitative oxidative coupling of sodium arylsulfinites for highly region-selective Heck-type reaction of allylic alcohols has been developed. The compatibility of the functionalities of -I, -Br, and -F would explore further postfunctionalization of the C-X bonds. This method provides a new and straightforward protocol for the synthesis of beta-aryl ketones and aldehydes. The deuterium labeling experiments indicated that this transformation may proceed via a [1, 2-H] shift process. PMID- 26282573 TI - Public health research in India in the new millennium: a bibliometric analysis. AB - BACKGROUND: Public health research has gained increasing importance in India's national health policy as the country seeks to address the high burden of disease and its inequitable distribution, and embarks on an ambitious agenda towards universalising health care. OBJECTIVE: This study aimed at describing the public health research output in India, its focus and distribution, and the actors involved in the research system. It makes recommendations for systematically promoting and strengthening public health research in the country. DESIGN: The study was a bibliometric analysis of PubMed and IndMed databases for years 2000 2010. The bibliometric data were analysed in terms of biomedical focus based on the Global Burden of Disease, location of research, research institutions, and funding agencies. RESULTS: A total of 7,893 eligible articles were identified over the 11-year search period. The annual research output increased by 42% between 2000 and 2010. In total, 60.8% of the articles were related to communicable diseases, newborn, maternal, and nutritional causes, comparing favourably with the burden of these causes (39.1%). While the burdens from non communicable diseases and injuries were 50.2 and 10.7%, respectively, only 31.9 and 7.5% of articles reported research for these conditions. The north-eastern states and the Empowered-Action-Group states of India were the most under represented for location of research. In total, 67.2% of papers involved international collaborations and 49.2% of these collaborations were with institutions in the UK or USA; 35.4% of the publications involved international funding and 71.2% of funders were located in the UK or USA. CONCLUSIONS: While public health research output in India has increased significantly, there are marked inequities in relation to the burden of disease and the geographic distribution of research. Systematic priority setting, adequate funding, and institutional capacity building are needed to address these inequities. PMID- 26282574 TI - Pulmonary arterial hypertension in a child with stage-IV neuroblastoma after autologous hematopoietic stem cell transplantation and review of the literature. AB - PH is a rare condition with high mortality rate after pediatric HSCT. As clinical presentation is non-specific and may mimic other conditions, a high degree of suspicion is required for diagnosis. Here, we present a patient with stage-IV neuroblastoma who developed PAH after autologous HSCT. After exclusion of other causes of PH, we regarded that this condition was secondary to HSCT. PMID- 26282575 TI - Parenting concerns, quality of life, and psychological distress in patients with advanced cancer. AB - OBJECTIVE: Parents with life-limiting illness anticipate the loss of their parental role and the long-term consequences of their illness on their children. The purpose of this study was to examine relationships between parenting concerns, quality of life (QOL), and symptoms of depression and anxiety in parents with advanced cancer who have dependent children. METHODS: Sixty-three parents diagnosed with a Stage IV solid malignancy completed the Hospital Anxiety Depression Scale (HADS), Parenting Concerns Questionnaire (PCQ), and Functional Assessment of Cancer Therapy-General (FACT-G). The Medical Outcomes Study Social Support Survey (social support) and Eastern Cooperative Oncology Group (ECOG) performance status were assessed as potential covariates. We performed descriptive statistics and multivariable linear regression models for depression, anxiety, and QOL measures. RESULTS: Mean PCQ score was 2.3 (SD 0.9), reflecting mild to moderate parenting concerns. Average depression and anxiety scores were 6.0 (SD 4.2) and 8.2 (SD 3.9), respectively. PCQ scores were associated with depressive symptoms (r = 0.46, p < 0.001), anxiety symptoms (r = 0.52, p < 0.0001), and QOL scores (r = -0.60, p < 0.001). The relationship of PCQ scores to anxiety symptoms (B = 1.5 p = 0.016) and QOL (B = -5.7, p = 0.02) remained significant after controlling for ECOG status, social support, and treatment status. CONCLUSIONS: Parenting concerns are associated with anxiety and depressive symptoms and worse QOL in parents diagnosed with advanced cancer. Further studies that evaluate how parental status affects coping and psychological distress in advanced cancer are needed.Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26282576 TI - Fast automated segmentation of wrist bones in magnetic resonance images. AB - PURPOSE: According to current recommendations in diagnostics of rheumatoid arthritis (RA), Magnetic resonance (MR) images of wrist joints are used to evaluate three main signs of RA: synovitis, bone edema and bone erosions. In this paper we present an efficient method for segmentation of 15 bones present on MR images of the wrist which is inevitable for future computer-assisted diagnosis system for RA lesions. METHOD: The segmentation procedure consists of two stages. The first stage is evaluation of markers (parts of bones working as seeds for the watershed algorithm) for bones in every joint: the distal parts of ulna and radius, the proximal parts of metacarpal bones and carpal bones. In the second stage the watershed from markers algorithm is applied based on the markers determined in the previous stage and the wrist bones are segmented. The markers were found using Multi Otsu algorithm along with custom method for filtering bones from other tissues. RESULTS: We analyzed 34 MR images. The automated segmentations were compared with manual segmentations using metrics: accuracy ACC derived from area under ROC curve AUC, Dice coefficient and mean absolute distance MAD. The mean (standard deviation) values of ACC, Dice and MAD were 0.99 (0.02), 0.98 (0.04) and 1.21 (0.39), respectively. CONCLUSION: The results of this study prove that our method is efficient and gives satisfactory results for segmentation of bones on low-field MR images of the wrist. PMID- 26282577 TI - Latencies from intracranial seizure onset to ictal tachycardia: A comparison to surface EEG patterns and other clinical signs. AB - OBJECTIVE: Information on the relative timing of electroencephalography (EEG) seizure onset, ictal tachycardia (ITC), and first other clinical seizure manifestations is crucial for an understanding of the potential benefit of ITC detection based closed-loop intervention systems for epilepsy treatment. This study analyzes the temporal relation of ITC, other clinical signs, and seizure onset in relation to intracranial and surface EEG. METHODS: Seventy-eight seizures with ITC from 13 patients undergoing invasive EEG recordings with simultaneous recordings of electrocardiography (ECG), intracranial EEG (iEEG) and surface EEG, and video recordings to determine clinical onset were analyzed. Latencies for ITC were calculated for thresholds of 100 bpm and for a 20% heart rate increase above baseline obtained 60 s prior to seizure onset on iEEG. Patient-based, seizure-based, and seizure origin-based analyses were performed. RESULTS: Mean latencies between seizure onset in invasive EEG and the following onset of ITC in the seizure- and patient-based analysis for both thresholds varied between 21.6 and 23.7 s, showing that ITC is an ictal rather a preictal phenomenon. In 10 of 13 patients and in 56 of 78 seizures, at least one of the thresholds for ITC was crossed before any other clinical sign. In the majority of cases, ITC also preceded ictal onset as determined in surface EEG. Latencies to ictal tachycardia were shorter for hippocampal than for extrahippocampal temporal seizure onset. ITC occurred earlier in right than in left temporal seizures. SIGNIFICANCE: iEEG preceded other seizure manifestations, but ictal tachycardia was an early sign particularly in mesial temporal and in right temporal seizure onset and often preceded not only other clinical manifestations but also first visible patterns in surface EEG. Detection of ictal tachycardia was thus the best noninvasively assessed marker for closed-loop interventions in this multimodally assessed patient group. PMID- 26282578 TI - Country logistics performance and disaster impact. AB - The aim of this paper is to deepen the understanding of the relationship between country logistics performance and disaster impact. The relationship is analysed through correlation analysis and regression models for 117 countries for the years 2007 to 2012 with disaster impact variables from the International Disaster Database (EM-DAT) and logistics performance indicators from the World Bank. The results show a significant relationship between country logistics performance and disaster impact overall and for five out of six specific logistic performance indicators. These specific indicators were further used to explore the relationship between country logistic performance and disaster impact for three specific disaster types (epidemic, flood and storm). The findings enhance the understanding of the role of logistics in a humanitarian context with empirical evidence of the importance of country logistics performance in disaster response operations. PMID- 26282579 TI - Is Aerogen-pi Interaction Capable of Initiating the Noncovalent Chemistry of Group 18? AB - The interactions between atoms of noble gases and pi systems are generally considered as van der Waals interaction, which have not attracted attention yet. Herein, we present high-level ab initio calculations to show the unexpected noncovalent interaction between a covalently bonded noble gas atom and a delocalized aromatic pi electron using XeO3?benzene as the prototype. The CCSD(T)/CBS reference data show its strength amounting to -10.2 kcal mol(-1), comparable to a typical H-bond or an anion-pi interaction. The energy decomposition analysis reveals that the aerogen-pi interaction is favored by the electrostatic interaction (27.7%), the induction (13.4%), and the dispersion (21.6%). This interaction may prompt us to consider the noncovalent chemistry of aerogen derivatives in the near future. PMID- 26282580 TI - Doxycycline reduces the migration of tuberous sclerosis complex-2 null cells - effects on RhoA-GTPase and focal adhesion kinase. AB - Lymphangioleiomyomatosis (LAM) is associated with dysfunction of the tuberous sclerosis complex (TSC) leading to enhanced cell proliferation and migration. This study aims to examine whether doxycycline, a tetracycline antibiotic, can inhibit the enhanced migration of TSC2-deficient cells, identify signalling pathways through which doxycycline works and to assess the effectiveness of combining doxycycline with rapamycin (mammalian target of rapamycin complex 1 inhibitor) in controlling cell migration, proliferation and wound closure. TSC2 positive and TSC2-negative mouse embryonic fibroblasts (MEF), 323-TSC2-positive and 323-TSC2-null MEF and Eker rat uterine leiomyoma (ELT3) cells were treated with doxycycline or rapamycin alone, or in combination. Migration, wound closure and proliferation were assessed using a transwell migration assay, time-lapse microscopy and manual cell counts respectively. RhoA-GTPase activity, phosphorylation of p70S6 kinase (p70S6K) and focal adhesion kinase (FAK) in TSC2 negative MEF treated with doxycycline were examined using ELISA and immunoblotting techniques. The enhanced migration of TSC2-null cells was reduced by doxycycline at concentrations as low as 20 pM, while the rate of wound closure was reduced at 2-59 MUM. Doxycycline decreased RhoA-GTPase activity and phosphorylation of FAK in these cells but had no effect on the phosphorylation of p70S6K, ERK1/2 or AKT. Combining doxycycline with rapamycin significantly reduced the rate of wound closure at lower concentrations than achieved with either drug alone. This study shows that doxycycline inhibits TSC2-null cell migration. Thus doxycycline has potential as an anti-migratory agent in the treatment of diseases with TSC2 dysfunction. PMID- 26282581 TI - GABAB receptor-mediated feed-forward circuit dysfunction in the mouse model of fragile X syndrome. AB - KEY POINTS: Cortico-hippocampal feed-forward circuits formed by the temporoammonic (TA) pathway exhibit a marked increase in excitation/inhibition ratio and abnormal spike modulation functions in Fmr1 knock-out (KO) mice. Inhibitory, but not excitatory, synapse dysfunction underlies cortico-hippocampal feed-forward circuit abnormalities in Fmr1 KO mice. GABA release is reduced in TA associated inhibitory synapses of Fmr1 KO mice in a GABAB receptor-dependent manner. Inhibitory synapse and feed-forward circuit defects are mediated predominately by presynaptic GABAB receptor signalling in the TA pathway of Fmr1 KO mice. GABAB receptor-mediated inhibitory synapse defects are circuit-specific and are not observed in the Schaffer collateral pathway-associated inhibitory synapses in stratum radiatum. ABSTRACT: Circuit hyperexcitability has been implicated in neuropathology of fragile X syndrome, the most common inheritable cause of intellectual disability. Yet, how canonical unitary circuits are affected in this disorder remains poorly understood. Here, we examined this question in the context of the canonical feed-forward inhibitory circuit formed by the temporoammonic (TA) branch of the perforant path, the major cortical input to the hippocampus. TA feed-forward circuits exhibited a marked increase in excitation/inhibition ratio and major functional defects in spike modulation tasks in Fmr1 knock-out (KO) mice, a fragile X mouse model. Changes in feed forward circuits were caused specifically by inhibitory, but not excitatory, synapse defects. TA-associated inhibitory synapses exhibited increase in paired pulse ratio and in the coefficient of variation of IPSPs, consistent with decreased GABA release probability. TA-associated inhibitory synaptic transmission in Fmr1 KO mice was also more sensitive to inhibition of GABAB receptors, suggesting an increase in presynaptic GABAB receptor (GABAB R) signalling. Indeed, the differences in inhibitory synaptic transmission between Fmr1 KO and wild-type (WT) mice were eliminated by a GABAB R antagonist. Inhibition of GABAB Rs or selective activation of presynaptic GABAB Rs also abolished the differences in the TA feed-forward circuit properties between Fmr1 KO and WT mice. These GABAB R-mediated defects were circuit-specific and were not observed in the Schaffer collateral pathway-associated inhibitory synapses. Our results suggest that the inhibitory synapse dysfunction in the cortico hippocampal pathway of Fmr1 KO mice causes hyperexcitability and feed-forward circuit defects, which are mediated in part by a presynaptic GABAB R-dependent reduction in GABA release. PMID- 26282582 TI - SRSF1 and hnRNP H antagonistically regulate splicing of COLQ exon 16 in a congenital myasthenic syndrome. AB - The catalytic subunits of acetylcholinesterase (AChE) are anchored in the basal lamina of the neuromuscular junction using a collagen-like tail subunit (ColQ) encoded by COLQ. Mutations in COLQ cause endplate AChE deficiency. An A-to-G mutation predicting p.E415G in COLQ exon 16 identified in a patient with endplate AChE deficiency causes exclusive skipping of exon 16. RNA affinity purification, mass spectrometry, and siRNA-mediated gene knocking down disclosed that the mutation disrupts binding of a splicing-enhancing RNA-binding protein, SRSF1, and de novo gains binding of a splicing-suppressing RNA-binding protein, hnRNP H. MS2 mediated artificial tethering of each factor demonstrated that SRSF1 and hnRNP H antagonistically modulate splicing by binding exclusively to the target in exon 16. Further analyses with artificial mutants revealed that SRSF1 is able to bind to degenerative binding motifs, whereas hnRNP H strictly requires an uninterrupted stretch of poly(G). The mutation compromised splicing of the downstream intron. Isolation of early spliceosome complex revealed that the mutation impairs binding of U1-70K (snRNP70) to the downstream 5' splice site. Global splicing analysis with RNA-seq revealed that exons carrying the hnRNP H binding GGGGG motif are predisposed to be skipped compared to those carrying the SRSF1-binding GGAGG motif in both human and mouse brains. PMID- 26282584 TI - Ambient carbon monoxide associated with alleviated respiratory inflammation in healthy young adults. AB - There is increasing controversy on whether acute exposure to ambient carbon monoxide (CO) is hazardous on respiratory health. We therefore performed a longitudinal panel study to evaluate the acute effects of ambient CO on fractional exhaled nitric oxide (FeNO), a well-established biomarker of airway inflammation. We completed 4-6 rounds of health examinations among 75 healthy young adults during April to June in 2013 in Shanghai, China. We applied the linear mixed-effect model to investigate the short-term associations between CO and FeNO. CO exposure during 2-72 h preceding health tests was significantly associated with decreased FeNO levels. For example, an interquartile range increase (0.3 mg/m(3)) of 2-h CO exposure corresponded to 10.6% decrease in FeNO. This association remained when controlling for the concomitant exposure to co pollutants. This study provided support that short-term exposure to ambient CO might be related with reduced levels of FeNO, a biomarker of lower airway inflammation. PMID- 26282583 TI - Objectively measured sedentary time, physical activity and kidney function in people with recently diagnosed Type 2 diabetes: a prospective cohort analysis. AB - AIM: To assess the prospective association between objectively measured physical activity and kidney function over 4 years in people with Type 2 diabetes. METHODS: Individuals (120 women and 206 men) participating in the ADDITION-Plus trial underwent assessment of sedentary time (SED-time), time spent in moderate to-vigorous-intensity physical activity (MVPA) and total physical activity energy expenditure (PAEE) using a combined heart rate and movement sensor, and kidney function [estimated glomerular filtration rate (eGFR), serum creatinine and urine albumin-to-creatinine ratio (ACR)] at baseline and after 4 years of follow-up. Multivariate regression was used to quantify the association between change in SED-time, MVPA and PAEE and kidney measures at four-year follow-up, adjusting for change in current smoking status, waist circumference, HbA1c , systolic blood pressure, triglycerides and medication usage. RESULTS: Over 4 years, there was a decline in eGFR values from 87.3 to 81.7 ml/min/1.73m(2) (P < 0.001); the prevalence of reduced eGFR (eGFR < 60 ml/min/1.73m(2) ) increased from 6.1 to 13.2% (P < 0.001). There were small increases in serum creatinine (median: 81-84 MUmol/l, P < 0.001) and urine ACR (median: 0.9-1.0 mg/mmol, P = 0.005). Increases in SED-time were associated with increases in serum creatinine after adjustment for MVPA and cardiovascular risk factors (beta = 0.013, 95% CI: 0.001, 0.03). Conversely, increases in PAEE were associated with reductions in serum creatinine (beta = -0.001, 95% CI: -0.003, -0.0001). CONCLUSION: Reducing time spent sedentary and increasing overall physical activity may offer intervention opportunities to improve kidney function among individuals with diabetes. (Trial Registry no. ISRCTN 99175498). PMID- 26282585 TI - On the use of numerical modelling for near-field pollutant dispersion in urban environments--A review. AB - This article deals with the state-of-the-art of experimental and numerical studies carried out regarding air pollutant dispersion in urban environments. Since the simulation of the dispersion field around buildings depends strongly on the correct simulation of the wind-flow structure, the studies performed during the past years on the wind-flow field around buildings are reviewed. This work also identifies errors that can produce poor results when numerically modelling wind flow and dispersion fields around buildings in urban environments. Finally, particular attention is paid to the practical guidelines developed by researchers to establish a common methodology for verification and validation of numerical simulations and/or to assist and support the users for a better implementation of the computational fluid dynamics (CFD) approach. PMID- 26282586 TI - Intraepidermal benign sebaceous neoplasm: apocrine poroma (hidroacanthoma simplex type) with extensive sebaceous differentiation with sebaceoma-like features. AB - We herein report a patient who clinically presented with a yellowish, flat plaque that histopathologically showed a benign lesion mainly composed of intraepidermal basaloid nests with sebaceous differentiation. This lesion was considered to be fundamentally apocrine poroma (hidroacanthoma simplex type) with sebaceous differentiation. Nests composed of typical poroid cells were seen, and the results of immunostaining for lumican supported this diagnosis and excluded the possibility of clonal seborrheic keratosis. The sebaceous differentiation in apocrine poromas mostly occurs in Pinkus type lesions, and is usually seen in only part of the lesions, as solitary, mature sebocytes within the poroma nests. However, our apocrine poroma case was unique not only in that sebaceous differentiation occurred in the hidroacanthoma simplex type, but also in that it was observed extensively (approximately 60% of the nests). We therefore called this lesion an 'intraepidermal benign sebaceous neoplasm'. Although it may be hard to differentiate sebaceous germinative cells (seen in sebaceoma) from poroid cells, in this case, some poroma nests could be judged to neighbor or contain the sebaceoma-like areas. Therefore, the presented apocrine poroma was considered to have some features of (intraepidermal and dermal) sebaceoma. PMID- 26282588 TI - Management of Wire Brush Bristle Ingestion: Review of Literature and Presentation of an Algorithm. AB - OBJECTIVES: To increase awareness of wire brush bristle ingestion, review the literature relating to wire brush bristle ingestion, and describe an algorithm for management of wire brush bristle foreign bodies as well as a technique for bedside removal. METHODS: The authors present a case of an accidental wire bristle ingestion that was successfully treated with bedside removal and describe a successful bedside technique for removal. For the literature review, the PubMed journal database and Google Scholar were queried using the search terms wire bristle, wire brush, grill brush, and grill bristle. RESULTS: Twenty-three wire brush ingestions with upper aerodigestive presentations were identified in the medical literature. Bedside visualization was attempted in 10 patients and successful in 5. The foreign body was able to be removed at the bedside in 3 of these patients. Two patients were managed conservatively. The authors developed an algorithm for management based on these literature findings. CONCLUSION: Wire brush bristle ingestion is increasingly common in the literature, and a definitive algorithm does not exist for management. The authors present an algorithm for management and describe a technique for successful removal at the bedside. PMID- 26282589 TI - Robot-Assisted Neck Dissection Through a Modified Facelift Incision. AB - OBJECTIVES: The aim of this study is to describe the feasibility as well as oncologic outcomes of robot-assisted neck dissection (RAND) through a modified facelift incision in an American population. STUDY DESIGN: Retrospective case series. SETTING: University tertiary care hospital. METHODS: All patients who underwent RAND between November 2012 and December 2014 were included. Medical records were reviewed for demographics, medical histories, staging, operative information, postoperative hospital course and complications, and oncologic outcomes. RESULTS: There were 11 RANDs identified among 10 patients. Five patients had known nodal metastasis at the time of surgery. Two patients had been previously irradiated. The average time of surgery was 284.4 +/- 72.3 minutes, including other associated procedures. The average lymph node yield was 28.5 +/- 9.3 nodes. There were no major complications. Average follow-up was 19.4 months. There was 1 supraclavicular recurrence in a previously irradiated patient. All patients are currently alive and without evidence of disease. CONCLUSIONS: Robot assisted neck dissection is a safe and feasible procedure that can be performed by surgeons with familiarity with neck dissection and robot-assisted surgery and who have been trained in RAND. Appropriate oncologic outcomes can be obtained in a patient wishing to avoid a noticeable scar. PMID- 26282590 TI - Evaluation of fatty acid synthase in prostate cancer recurrence: SUV of [(11) C]acetate PET as a prognostic marker. AB - AIM: High levels of fatty acid synthase have shown to correlate with the aggressiveness of prostate cancer. As [(11) C]acetate exhibits a close correlation with the level of fatty acid synthase, we aimed to assess whether the SUV in [(11) C]acetate PET serves as a suitable prognostic marker in patients with recurrent prostate cancer. MATERIALS AND METHODS: In 123 consecutive patients, examined between 2010 and 2014, the maximum standardized uptake value (SUVmax) of local recurrences as well as lymph node and bone metastases was measured. Choosing the spleen as a standard for relatively high physiological uptake, a ratio of tumor to spleen uptake (SUVts) was calculated for standardizing the uptake, too. The corresponding initial Gleason scores (GS) and serum-PSA levels around the time of the performed PET/CT for each patient were retrospectively collected and PSA doubling together with PSA velocity were determined. For further analysis patients were divided with regard to their initial Gleason score (<=3 + 4 and >= 4 + 3). The median of PSA velocity was calculated to separate patients with a high and low PSA velocity and Mann-Whitney U or Student's t-test were used, testing for significant differences. For correlation Spearmen-Rho test was used. RESULTS: PET was positive for recurrence in 82/123 patients. PSA was significantly higher in PET-positive than in negative patients (5.9 vs. 3.2 ng/ml; P = 0.006). Initial Gleason score did not differ in PET negative and positive patients (P = 0.3), whereas PSA velocity was markedly higher in PET positive patients (0.4 vs. 0.1 ng/ml/month; P = 0.01). Median SUVmax of PET positive patients was 5.23 (mean 5.78; range 0.9-16.8) and meadian SUVts was 0.78 (mean 0.84, range 0.14-2.50). SUVts was significantly higher in patients with high PSA velocity (SUVts 0.76 vs. 0.92; P = 0.009), whereas SUVmax failed statistical significance (5.4 vs. 6.3 ng/ml/month; P = 0.08). Patients with a high SUVmax proved to have a significantly higher median Gleason score compared to low uptake 8.0 vs. 7.0; P = 0.004). Vice versa both SUVmax (GS 6: 5.0; GS 7: 5.6; GS 8: 5.7; GS 9: 6.5; r = 0.30, P = 0.008) and SUVts (GS 6: 0.63; GS 7: 0.68; GS 8: 0.85; GS 9: 0.89; r = 0.30, P = 0.006) significantly correlated with Gleason score. Patients with a Gleason score <= 3 + 4 had a significantly lower SUVmax (4.8 vs. 5.7; P = 0.02) and SUVts (0.67 vs. 0.85; P = 0.02) as compared to a Gleason score >= 4 + 3. CONCLUSION: [(11) C]acetate uptake demonstrated to correlate with initial Gleason score. Furthermore, patients with a high PSA velocity proved to have higher [(11) C]acetate uptake in tumor lesions. PMID- 26282591 TI - Downregulation of Hepatic Carbonyl Reductase Type 1 in End-Stage Renal Disease. AB - The functional expression of several hepatic drug metabolizing enzymes and transporters are altered in patients with end-stage renal disease (ESRD). We aimed to assess the effect of ESRD on the expression and function of hepatic reductases. Cytosolic and microsomal fractions were isolated from liver tissue from deceased ESRD (n=10) and deceased control patients (n=11). Gene and protein expression, and metabolic activity of reductases were assessed by conducting qRT PCR, Western blotting and enzyme kinetics, respectively. A 65% decrease in carbonyl reductase 1 protein expression (p<0.05), and a trend toward decreased reductase mRNA expression and activity was observed in ESRD livers versus controls. These results demonstrate a trend toward decreased functional expression of selective hepatic reductases in ESRD livers, which may partially explain altered pharmacokinetics of CBR1 drug substrates in ESRD. Future studies with larger sample size are warranted to confirm these findings. PMID- 26282592 TI - A Novel Plated Hepatocyte Relay Assay (PHRA) for In Vitro Evaluation of Hepatic Metabolic Clearance of Slowly Metabolized Compounds. AB - OBJECTIVE: Development and validation of a novel assay, the Plated Hepatocyte Relay Assay (PHRA), for the determination of the metabolic fates of slowly metabolized compounds. METHOD: Cryopreserved human hepatocytes were cultured for 4 h followed by incubation with slowly metabolized compounds for 24 h (initial incubation). On the next day, the incubated media were collected and added to hepatocytes was similarly prepared on the day of incubation (48 h incubation; 1(st) relay). The procedures were repeated on the next days (72 h (2(nd) relay), 96 h (3rd relay), and 120 h (4(th) relay) incubations). RESULTS: A proof-of concept study with two low clearance compounds, diazepam and tolbutamide, and a validation study with 15 ultra-low clearance compounds (CLnon-renal < 1 mL/min/kg) and low clearance compounds (CLnon-renal 1- 5.1 mL/min/kg) were performed. Linear time-dependent disappearance of the parent compounds was observed for all compounds. Application of published free fraction values in combination with a correction factor with in vitro hepatic clearance results obtained with the PHRA accurately predicted in vivo hepatic clearance. CONCLUSION: PHRA represents a useful experimental system for the evaluation of the metabolic fates of low clearance compounds in drug development. PMID- 26282594 TI - International expert opinion on the management of infection caused by azole resistant Aspergillus fumigatus. AB - An international expert panel was convened to deliberate the management of azole resistant aspergillosis. In culture-positive cases, in vitro susceptibility testing should always be performed if antifungal therapy is intended. Different patterns of resistance are seen, with multi-azole and pan-azole resistance more common than resistance to a single triazole. In confirmed invasive pulmonary aspergillosis due to an azole-resistant Aspergillus, the experts recommended a switch from voriconazole to liposomal amphotericin B (L-AmB; Ambisome((r))). In regions with environmental resistance rates of >=10%, a voriconazole-echinocandin combination or L-AmB were favoured as initial therapy. All experts recommended L AmB as core therapy for central nervous system aspergillosis suspected to be due to an azole-resistant Aspergillus, and considered the addition of a second agent with the majority favouring flucytosine. Intravenous therapy with either micafungin or L-AmB given as either intermittent or continuous therapy was recommended for chronic pulmonary aspergillosis due to a pan-azole-resistant Aspergillus. Local and national surveillance with identification of clinical and environmental resistance patterns, rapid diagnostics, better quality clinical outcome data, and a greater understanding of the factors driving or minimising environmental resistance are areas where research is urgently needed, as well as the development of new oral agents outside the azole drug class. PMID- 26282595 TI - Involvement of resveratrol in crosstalk between adipokine adiponectin and hepatokine fetuin-A in vivo and in vitro. AB - Metabolic homeostasis is maintained by the coordinated regulation of several physiological processes and organ crosstalk. Especially, the interaction between adipose tissue and liver is critical for the regulation of glucose and lipid metabolism. This study investigated the involvement of resveratrol (RSV) in the crosstalk between adipokine adiponectin and hepatokine fetuin-A. Adipocytes hepatocytes co-culture system and a high-fat (HF) diet-induced obesity (DIO) mouse model were utilized. Protein levels of adiponectin and fetuin-A were analyzed in adipocytes and hepatocytes with the knockdown of adiponectin and fetuin-A, respectively. After six weeks of the HF diet treatment, RSV was delivered via an osmotic pump for four weeks. The experimental groups were lean control fed with a standard diet, HF diet-induced obese control and HF_RSV (8 mg/kg/day). After 4 weeks of each treatment, blood and tissues were collected, and the levels of adiponectin and fetuin-A were analyzed. RNA interference during co-culture of adipocytes and hepatocytes demonstrated the existence of crosstalk between adiponectin and fetuin-A. The four-week RSV treatment resulted in increased serum adiponectin and decreased serum fetuin-A in diet-induced obesity mice. The serum levels of adiponectin and fetuin-A were inversely related. In epididymal fat depots, RSV increased adiponectin, peroxisome proliferator activated receptor (PPAR) alpha, PPAR gamma, sirtuin1 and AMP-activated protein kinase (AMPK). RSV lowered fetuin-A and NF-kappaB, and increased liver AMPK. These results demonstrate the crosstalk between adiponectin and fetuin-A, and suggest that RSV may be involved in adipose tissue and liver crosstalk through the interaction between adiponectin and fetuin-A. PMID- 26282596 TI - Chronic intermittent toluene inhalation in adolescent rats results in metabolic dysfunction with altered glucose homeostasis. AB - BACKGROUND AND PURPOSE: Abuse of toluene-containing inhalants is an increasing public health problem, especially among adolescents. Abuse during adolescence is associated with emaciation, while industrial exposure leads to altered glycaemic control suggesting metabolic instability. However, the relationship between adolescent inhalant abuse and metabolic dysfunction remains unknown. EXPERIMENTAL APPROACH: To model human abuse patterns, we exposed male adolescent Wistar rats [postnatal day (PND) 27] to chronic intermittent inhaled toluene (CIT, 10,000 ppm) or air (control) for 1 h.day(-1) , three times a week for 4 weeks. Feeding and body composition were monitored. After 4 weeks, circulating metabolic hormone concentrations and responses to a glucose tolerance test (GTT) were measured. Dietary preference was measured by giving animals access to either a 'western diet' plus standard chow (WC + SC) or standard chow alone during 4 weeks of abstinence. Metabolic hormones and GTT were subsequently measured. KEY RESULTS: Adolescent CIT exposure significantly retarded weight gain, altered body composition, circulating metabolic hormones and responses to a GTT. While reduced body weight persisted, responses to a GTT and circulating hormones appeared to normalize for animals on standard chow following abstinence. In CIT-exposed WC + SC rats, we observed impaired glucose tolerance associated with altered metabolic hormones. Analysis of hypothalamic genes revealed differential expression profiles in CIT-exposed rats following both the exposure period and abstinence, suggesting a central contribution to inhalant-induced metabolic dysfunction. CONCLUSION AND IMPLICATIONS: CIT exposure during adolescence has long-term effects on metabolic function, which may increase the risk of disorders related to energy balance and glycaemic control. PMID- 26282597 TI - Fluorimetric assays for N-acetylgalactosamine-6-sulfatase and arylsulfatase B based on the natural substrates for confirmation of mucopolysaccharidoses types IVA and VI. AB - BACKGROUND: Treatments have been developed for mucopolysaccharidoses IVA (MPS IVA) and MPS VI suggesting the need for eventual newborn screening. Biochemical enzyme assays are important for diagnosis. Previously reported fluorimetric assays of the relevant enzymes are based on substrates with poor activity or specificity. METHODS: We developed new fluorimetric assays for N acetylgalactosamine-6-sulfatase (GALNS) and arylsulfatase B (ARSB) based on the natural substrates, N-acetylgalactosamine-6-sulfate (and 4-sulfate), which have improved activity and specificity toward the relevant enzymes. The new substrates were tested on dried blood spots on newborn screening cards, and assays showed acceptable linearity in response with the amount of enzyme present (using quality control samples). RESULTS: When tested on dried blood spots from random newborns and affected patients, the assays showed good discrimination between the 2 sample groups. CONCLUSIONS: The analytical range of the new fluorimetric assays, defined as the ratio of enzyme-dependent-to-enzyme-independent assay response, is likely to be insufficient to use these assays for newborn screening. Rather, these new fluorimetric assays should be useful in a diagnostic lab to confirm a diagnosis via biochemical enzyme testing. PMID- 26282598 TI - The changing face of gestational diabetes: the effect of the shift from risk factor-based to comprehensive screening. AB - OBJECTIVE: To evaluate the effect of the change in the gestational diabetes (GDM) screening policy from risk-factor based to comprehensive screening on the prevalence and type of GDM and characteristics of GDM pregnancies. DESIGN: Population-based register study in Finland. Subjects were GDM women who gave birth before (2006, n=5185) and after (2010, n=6683) the policy change. All the other women in those years without pre-pregnancy diabetes acted as controls (51 759 and 52 398 respectively). METHODS: GDM women with singleton pregnancy were identified through The Finnish Medical Birth Register by abnormal oral glucose tolerance test or initiation of insulin. Main outcome measures were prevalence of GDM (total and insulin/diet-treated), and caesarean section rate. RESULTS: The proportion of screened mothers increased from 27.5 to 51.3% and the total prevalence of GDM from 9.1 to 11.3%. This increase consisted mainly of diet treated mothers, while the number and proportion of insulin-treated mothers decreased (21.8% vs13.3%, P<0.001). The proportion of primiparous women increased (34.5-39.4%, P<0.0001) and mean pre-pregnancy BMI decreased (28.6-28.2, P<0.001). The overall caesarean section rate remained the same but increased among women with GDM (20.8-22.1%) adjusted odds ratios being 1.22 (95% CI 1.14, 1.31) during comprehensive and 1.10 (95% CI 1.02, 1.19) during risk factor-based screening. CONCLUSIONS: The shift to comprehensive screening led to a significant increase in women with GDM, who were more often primiparous and had a lower BMI. Comprehensive screening did not perform better in diagnosing women needing insulin treatment. PMID- 26282599 TI - Subclinical hypercortisolism: a state, a syndrome, or a disease? AB - Subclinical hypercortisolism (SH), defined as alterations of the hypothalamus pituitary-adrenal axis in the absence of clinical signs or symptoms related to cortisol secretion, is a common finding in patients with adrenal incidentalomas. The clinical correlates of this pathological condition have become clearer over the last few years. The aim of this review is to summarize the co-morbidities and the clinical outcomes of patients with SH. According to the analysis of the results of the studies published within the last 15 years, hypertension and type 2 diabetes are a common finding in patients with SH, occurring roughly in 2/3 and 1/3 of the patients respectively. Moreover, several additional cardiovascular and metabolic complications, like endothelial damage, increased visceral fat accumulation and impaired lipid metabolism have been shown to increase the cardiovascular risk of those patients. Accordingly, recent independent reports investigating the natural history of the disease in a long-term follow-up setting have shown that patients with SH have a higher incidence of cardiovascular events and related mortality. Moreover, longitudinal studies have also shown increased incidence of osteoporotic vertebral fractures. Future research is needed to improve the diagnostic performance of hormonal tests, by assessment of the complete steroid profile with more accurate assays, and to define the efficacy of surgical vs medical treatment in a randomized-controlled setting. PMID- 26282600 TI - Surfactant-enhanced spreading: Experimental achievements and possible mechanisms. AB - Surfactants are broadly used to improve wetting properties of aqueous formulations. The improvement is achieved by essential reduction of liquid/air and solid/liquid interfacial tensions resulting in the decrease of contact angle. For moderately hydrophobic substrates, there is a range of surfactants providing complete wetting of substrate. With the decrease of substrate surface energy, this range of surfactants reduces very quickly and only trisiloxane surfactant solutions are capable to wet completely such highly hydrophobic substrates as polypropylene and parafilm. That is why these surfactants are referred to as superspreaders. The most intriguing feature of wetting surfactant solutions is their ability to spread much faster than pure liquids with spread area, S, being proportional to time, t, S~t, as compared to S~t(0.2) for pure liquids, which wet completely the solid substrate. Trisiloxane surfactant solutions spread faster than other aqueous surfactant solutions, which also provide complete wetting, being superspreaders in the sense of spreading rate as well. The mechanism of fast spreading of surfactant solutions on hydrophobic substrates and much higher spreading rates for trisiloxane solutions are to be explained. Below the available experimental data on superspreading and surfactant-enhanced spreading are analysed/summarised, and possible mechanisms governing the fast spreading are discussed. PMID- 26282601 TI - BMP signalling differentially regulates distinct haematopoietic stem cell types. AB - Adult haematopoiesis is the outcome of distinct haematopoietic stem cell (HSC) subtypes with self-renewable repopulating ability, but with different haematopoietic cell lineage outputs. The molecular basis for this heterogeneity is largely unknown. BMP signalling regulates HSCs as they are first generated in the aorta-gonad-mesonephros region, but at later developmental stages, its role in HSCs is controversial. Here we show that HSCs in murine fetal liver and the bone marrow are of two types that can be prospectively isolated--BMP activated and non-BMP activated. Clonal transplantation demonstrates that they have distinct haematopoietic lineage outputs. Moreover, the two HSC types differ in intrinsic genetic programs, thus supporting a role for the BMP signalling axis in the regulation of HSC heterogeneity and lineage output. Our findings provide insight into the molecular control mechanisms that define HSC types and have important implications for reprogramming cells to HSC fate and treatments targeting distinct HSC types. PMID- 26282602 TI - Caloric vestibular stimulation modulates nociceptive evoked potentials. AB - Vestibular stimulation has been reported to alleviate central pain. Clinical and physiological studies confirm pervasive interactions between vestibular signals and somatosensory circuits, including nociception. However, the neural mechanisms underlying vestibular-induced analgesia remain unclear, and previous clinical studies cannot rule out explanations based on alternative, non-specific effects such as distraction or placebo. To investigate how vestibular inputs influence nociception, we combined caloric vestibular stimulation (CVS) with psychophysical and electrocortical responses elicited by nociceptive-specific laser stimulation in humans (laser-evoked potentials, LEPs). Cold water CVS applied to the left ear resulted in significantly lower subjective pain intensity for experimental laser pain to the left hand immediately after CVS, relative both to before CVS and to 1 h after CVS. This transient reduction in pain perception was associated with reduced amplitude of all LEP components, including the early N1 wave reflecting the first arrival of nociceptive input to primary somatosensory cortex. We conclude that cold left ear CVS elicits a modulation of both nociceptive processing and pain perception. The analgesic effect induced by CVS could be mediated either by subcortical gating of the ascending nociceptive input, or by direct modulation of the primary somatosensory cortex. PMID- 26282603 TI - Reversible heart rhythm complexity impairment in patients with primary aldosteronism. AB - Excess aldosterone secretion in patients with primary aldosteronism (PA) impairs their cardiovascular system. Heart rhythm complexity analysis, derived from heart rate variability (HRV), is a powerful tool to quantify the complex regulatory dynamics of human physiology. We prospectively analyzed 20 patients with aldosterone producing adenoma (APA) that underwent adrenalectomy and 25 patients with essential hypertension (EH). The heart rate data were analyzed by conventional HRV and heart rhythm complexity analysis including detrended fluctuation analysis (DFA) and multiscale entropy (MSE). We found APA patients had significantly decreased DFAalpha2 on DFA analysis and decreased area 1-5, area 6-15, and area 6-20 on MSE analysis (all p < 0.05). Area 1-5, area 6-15, area 6-20 in the MSE study correlated significantly with log-transformed renin activity and log-transformed aldosterone-renin ratio (all p < = 0.01). The conventional HRV parameters were comparable between PA and EH patients. After adrenalectomy, all the altered DFA and MSE parameters improved significantly (all p < 0.05). The conventional HRV parameters did not change. Our result suggested that heart rhythm complexity is impaired in APA patients and this is at least partially reversed by adrenalectomy. PMID- 26282604 TI - Innovation is mandatory in chronic type B aortic dissection. PMID- 26282605 TI - The no-touch saphenous vein for coronary artery bypass grafting maintains a patency, after 16 years, comparable to the left internal thoracic artery: A randomized trial. AB - OBJECTIVES: This study investigates whether the no-touch (NT) vein graft, at a mean time of 16 years, maintains a significantly higher patency rate than conventional (C) vein grafts and still has patency comparable to that of the left internal thoracic artery (LITA). METHODS: A total of 156 patients accepted for coronary artery bypass grafting were randomly allocated to 1 of 3 groups. In the C group, the saphenous vein (SV) was stripped and distended. In the intermediate group, the SV was stripped but not distended. In the NT group, the SV was neither stripped nor distended, but rather harvested with a fat pedicle. This study is an angiographic follow-up of the C and NT groups, at a mean time of 16 years postoperatively. RESULTS: Fifty-four patients were included (C group = 27; NT group = 27). In all, 72 and 75 vein grafts were completed in groups C and NT, respectively. Crude SV graft patency was 64% in the C group versus 83% in the NT group (P = .03), which was similar to the patency of the LITA (88%). The harvesting technique had a major impact on the patency with a hazard ratio for occlusion of 1.83 for the C group (P = .04). CONCLUSIONS: Harvesting the SV with the NT technique conferred, at a mean time of 16 years, a significantly higher patency than the conventional technique that was still comparable to that of the LITA. PMID- 26282606 TI - Lung adenocarcinoma: Are skip N2 metastases different from non-skip? AB - OBJECTIVE: This study investigated the association between clinical pathologic features, especially adenocarcinoma subtypes and prognosis, and skip N2 metastasis in patients with lung adenocarcinoma. METHODS: In this study, 177 patients with lung adenocarcinoma and N2 metastasis were enrolled. Patients who had N2 lymph node metastases without N1 lymph node involvement were defined as skip N2 and otherwise as non-skip N2. We investigated the difference of clinicopathologic characteristics, recurrence-free survival, overall survival, and spectrum of well-identified molecular alterations in EGFR, KRAS, HER2, BRAF, ALK, ROS1, and RET genes in the 2 groups. RESULTS: Skip N2 metastasis was found in 45 patients, in whom a remarkably lower incidence of lymphovascular invasion was revealed (P = .01). Skip N2 metastasis was also associated with acinar subtype, good differentiation, and right lung cancer. The recurrence-free survival and overall survival were significantly better in the skip N2 group (5 year recurrence-free survival 37.4% vs 5.7%; log-rank P = .005; 5-year overall survival 60.7% vs 32.1%; log-rank P = .024). The predictive value of skip N2 was more significant in patients with lesions in the right lung (5-year recurrence free survival 36.6% vs 0.0%; log-rank P = .002; 5-year overall survival 57.2% vs 27.9%; log-rank P = .016) and in patients whose tumor diameter was no more than 3 cm (5-year recurrence-free survival 43.1% vs 6.7%; log-rank P = .01; 5-year overall survival 74.6 vs 27.6%; log-rank P = .04). CONCLUSIONS: There are distinct differences in clinicopathologic features and prognosis in patients with or without skip N2 metastasis. Considering the results of our study, subclassifications of mediastinal lymph node metastases could have clinical significance for patients with lung adenocarcinoma. PMID- 26282607 TI - Pushing, pulling, or Seldinger technique: What matters is understanding the principles, not the methods. PMID- 26282608 TI - Altered left ventricular vortex ring formation by 4-dimensional flow magnetic resonance imaging after repair of atrioventricular septal defects. AB - OBJECTIVES: During normal left ventricular (LV) filling, a vortex ring structure is formed distal to the left atrioventricular valve (LAVV). Vortex structures contribute to efficient flow organization. We aimed to investigate whether LAVV abnormality in patients with a corrected atrioventricular septal defect (AVSD) has an impact on vortex ring formation. METHODS: Whole-heart 4D flow MRI was performed in 32 patients (age: 26 +/- 12 years), and 30 healthy subjects (age: 25 +/- 14 years). Vortex ring cores were detected at peak early (E-peak) and peak late filling (A-peak). When present, the 3-dimensional position and orientation of the vortex ring was defined, and the circularity index was calculated. Through plane flow over the LAVV, and the vortex formation time (VFT), were quantified to analyze the relationship of vortex flow with the inflow jet. RESULTS: Absence of a vortex ring during E-peak (healthy subjects 0%, vs patients 19%; P = .015), and A-peak (healthy subjects 10% vs patients 44%; P = .008) was more frequent in patients. In 4 patients, this was accompanied by a high VFT (5.1-7.8 vs 2.4 +/- 0.6 in healthy subjects), and in another 2 patients with abnormal valve anatomy. In patients compared with controls, the vortex cores had a more-anterior and apical position, closer to the ventricular wall, with a more-elliptical shape and oblique orientation. The shape of the vortex core closely resembled the valve shape, and its orientation was related to the LV inflow direction. CONCLUSIONS: This study quantitatively shows the influence of abnormal LAVV and LV inflow on 3D vortex ring formation during LV inflow in patients with corrected AVSD, compared with healthy subjects. PMID- 26282609 TI - Selective transfer of polyunsaturated fatty acids from phytoplankton to planktivorous fish in large boreal lakes. AB - Lake size influences various hydrological parameters, such as water retention time, circulation patterns and thermal stratification that can consequently affect the plankton community composition, benthic-pelagic coupling and the function of aquatic food webs. Although the socio-economical (particularly commercial fisheries) and ecological importance of large lakes has been widely acknowledged, little is known about the availability and trophic transfer of polyunsaturated fatty (PUFA) in large lakes. The objective of this study was to investigate trophic trajectories of PUFA in the pelagic food web (seston, zooplankton, and planktivorous fish) of six large boreal lakes in the Finnish Lake District. Docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and alpha linolenic acid (ALA) were the most abundant PUFA in pelagic organisms, particularly in the zooplanktivorous fish. Our results show that PUFA from the n 3 family (PUFAn-3), often associated with marine food webs, are also abundant in large lakes. The proportion of DHA increased from ~4+/-3% in seston to ~32+/-6% in vendace (Coregonus albula) and smelt (Osmerus eperlanus), whereas ALA showed the opposite trophic transfer pattern with the highest values observed in seston (~11+/-2%) and the lowest in the opossum shrimp (Mysis relicta) and fish (~2+/ 1%). The dominance of diatoms and cryptophytes at the base of the food web in the study lakes accounted for the high amount of PUFAn-3 in the planktonic consumers. Furthermore, the abundance of copepods in the large lakes explains the effective transfer of DHA to planktivorous fish. The plankton community composition in these lakes supports a fishery resource (vendace) that is very high nutritional quality (in terms of EPA and DHA contents) to humans. PMID- 26282610 TI - Examination of the Adlerian constructs of activity and social interest with depression among recent Korean retirees: Meaning in life as a mediator. AB - The purpose of the present study was to investigate whether (a) the Adlerian construct of activity and social interest would be related to decreased depression and (b) meaning in life would mediate these relationships among Korean retirees. A total of 219 Korean retirees who had retired within the last three years completed the survey. The survey included the Activity Scale, Social Interest Scale, The Meaning in Life Questionnaire, and Center for Epidemiology Depression Scale. Structural equation modeling was conducted to analyze data. The results indicated that activity was directly associated with depression (beta= .453, p<.001) and indirectly related to depression through meaning in life (indirect path: beta=-.279, p< .05, 95% CI=-.483, ~-.145). Similarly, social interest was found to be directly related to depression (beta=-.710, p<.001) and indirectly related to depression through meaning in life (indirect path: beta= .227, p<.05, 95% CI=-.427, ~-.086). These findings suggest that meaning in life is an important avenue through which activity and social interest are linked to a lower level of depression among Korean retirees. PMID- 26282611 TI - From cloned frogs to patient matched stem cells: induced pluripotency or somatic cell nuclear transfer? AB - Nuclear transfer has seen a remarkable comeback in the past few years. Three groups have independently reported the derivation of stem cell lines by somatic cell nuclear transfer, from either adult, neonatal or fetal cells. Though the ability of human oocytes to reprogram somatic cells to stem cells had long been anticipated, success did not arrive on a straightforward path. Little was known about human oocyte biology, and nuclear transfer protocols developed in animals required key changes to become effective with human eggs. By overcoming these challenges, human nuclear transfer research has contributed to a greater understanding of oocyte biology, provided a point of reference for the comparison of induced pluripotent stem cells, and delivered a method for the generation of personalized stem cells with therapeutic potential. PMID- 26282612 TI - Inhibitory role of ERbeta on anterior pituitary cell proliferation by controlling the expression of proteins related to cell cycle progression. AB - Considering that the role of ERbeta in the growth of pituitary cells is not well known, the aim of this work was to determine the expression of ERbeta in normal and tumoral cells and to investigate its implications in the proliferative control of this endocrine gland, by analyzing the participation of cyclin D1, Cdk4 and p21. Our results showed that the expression of ERbeta decreased during pituitary tumoral development induced by chronic E2 stimulation. The 20 +/- 1.6% of normal adenohypophyseal cells expressed ERbeta, with this protein being reduced in the hyperplastic/adenomatous pituitary: at 20 days the ERbeta+ population was 10.7 +/- 2.2%, while after 40 and 60 days of treatment an almost complete loss in the ERbeta expression was observed (40 d: 1 +/- 0.6%; 60 d: 2 +/ 0.6%). The ERalpha/beta ratio increased starting from tumors at 40 days, mainly due to the loss of ERbeta expression. The cell proliferation was analyzed in normal and hyperplastic pituitary and also in GH3beta- and GH3beta+ which contained different levels of ERbeta expression, and therefore different ERalpha/beta ratios. The over-expression of ERbeta inhibited the GH3 cell proliferation and expression of cyclin D1 and ERalpha. Also, the ERbeta activation by its agonist DPN changed the subcellular localization of p21, inducing an increase in the p21 nuclear expression, where it acts as a tumoral suppressor. These results show that ERbeta exerts an inhibitory role on pituitary cell proliferation, and that this effect may be partially due to the modulation of some key regulators of the cell cycle, such as cyclin D1 and p21. These data contribute significantly to the understanding of the ER effects in the proliferative control of pituitary gland, specifically related to the ERbeta function in the E2 actions on this endocrine gland. PMID- 26282613 TI - Unique genomic organization of a novel Avipoxvirus detected in turkey (Meleagris gallopavo). AB - Avipoxviruses are emerging pathogens affecting over 200 bird species worldwide. Genetic characterization of avipoxviruses is performed by analysis of genomic regions encoding the 4b and DNA polymerase. Whole genome sequence data are limited to a few avipoxvirus isolates. Based on phylogenetic analysis three major genetic clades are distinguished. In this study we report a novel avipoxvirus strain causing skin lesions in domestic turkey. The virus was identified in Hungary during 2011 in a flock of turkey vaccinated against avipoxvirus infection. The genome of the isolated strain, TKPV-HU1124/2011, was uniquely short (~188.5kbp) and was predicted to encode reduced number of proteins. Phylogenetic analysis of the genes encoding the 4b and DNA polymerase separated TKPV-HU1124/2011 from other turkey origin avipoxviruses and classified it into a new genetic clade. This study permits new insight into the genetic and genomic heterogeneity of avipoxviruses and pinpoints the importance of strain diversity in vaccine efficacy. PMID- 26282614 TI - Damage and protection of the photosynthetic apparatus from UV-B radiation. II. Effect of quercetin at different pH. AB - The effect of the exogenously added quercetin against the UV-B inhibition of the photosystem II (PSII) functions in isolated pea thylakoid membranes suspended at different pH of the medium (6.5, 7.6 and 8.4) was investigated. The data revealed that the interaction of this flavonoid with the membranes depends on the pH and influences the initial S0-S1 state distribution of PSII in the dark, the energy transfer between pigment-protein complexes of the photosynthetic apparatus and the membrane fluidity. Quercetin also displays a different UV-protective effect depending on its location in the membranes, as the effect is more pronounced at pH 8.4 when it is located at the membrane surface. The results suggest that quercetin induces structural changes in thylakoid membranes, one of the possible reasons for its protection of the photosynthetic apparatus. PMID- 26282615 TI - Retraction Note to: Gene expression profiling analysis of locus coeruleus in idiopathic Parkinson's disease by bioinformatics. PMID- 26282616 TI - Retraction Note to: Gene expression analyses to explore the biomarkers and therapeutic targets for gliomas. PMID- 26282617 TI - Retraction Note to: Association of Catechol-O-methyltransferase val/met polymorphism with cognitive function in Gilles de la Tourette syndrome patients. PMID- 26282618 TI - How women with high risk pregnancies use lay information when considering place of birth: A qualitative study. AB - INTRODUCTION: Where to give birth is a key decision in pregnancy. Women use information from family, friends and other sources besides healthcare professionals when contemplating this decision. This study explored women's use of lay information during high risk pregnancies in order to examine differences and similarities in the use of information in relation to planned place of birth. Half the participants were planning hospital births and half were planning to give birth at home. METHODS: A qualitative study using semi-structured interviews set in a hospital maternity department in South East England. Twenty-six participants with high risk pregnancies, at least 32 weeks pregnant. Results were analysed using thematic analysis. RESULTS: Three themes emerged: approaches to research - how much information women chose to seek out and from which sources; selection of sources - how women decided which sources they considered reliable; and unhelpful research - information they considered unhelpful. Women planning homebirths undertook more research than women planning to give birth in hospital and were more likely to seek out alternative sources of information. Women from both groups referred to deliberately seeking out sources of information which reflected their own values and so did not challenge their decisions. CONCLUSIONS: There are similarities and differences in the use of lay information between women who plan to give birth in hospital and those who plan homebirths. Professionals working with women with high risk pregnancies should consider these factors when interacting with these women. PMID- 26282619 TI - Formulating policy activities to promote healthy and sustainable diets. AB - OBJECTIVE: To develop a policy formulation tool for strategically informing food and nutrition policy activities to promote healthy and sustainable diets (HSD). DESIGN: A policy formulation tool consisting of two complementary components was developed. First, a conceptual framework of the environment-public health nutrition relationship was constructed to characterise and conceptualise the food system problem. Second, an 'Orders of Food Systems Change' schema drawing on systems dynamics thinking was developed to identify, assess and propose policy options to redesign food systems. SETTING: Food and nutrition policy activities to promote HSD have been politicised, fragmented and lacking a coherent conceptual and strategic focus to tackle complex food system challenges. RESULTS: The tool's conceptual framework component comprises three integrated dimensions: (i) a structure built around the environment and public health nutrition relationship that is mediated via the food system; (ii) internal mechanisms that operate through system dynamics; and (iii) external interactions that frame its nature and a scope within ecological parameters. The accompanying schema is structured around three orders of change distinguished by contrasting ideological perspectives on the type and extent of change needed to 'solve' the HSD problem. CONCLUSIONS: The conceptual framework's systems analysis of the environment public health nutrition relationship sets out the food system challenges for HSD. The schema helps account for political realities in policy making and is a key link to operationalise the framework's concepts to actions aimed at redesigning food systems. In combination they provide a policy formulation tool to strategically inform policy activities to redesign food systems and promote HSD. PMID- 26282621 TI - Impacts of a newly identified behaviour-altering trematode on its host amphipod: from the level of gene expression to population. AB - Changes to host behaviour induced by some trematode species, as a means of increased trophic transmission, represents one of the seminal examples of host manipulation by a parasite. The amphipod Echinogammarus marinus (Leach, 1815) is infected with a previously undescribed parasite, with infected individuals displaying positive phototaxic and negative geotaxic behaviour. This study reveals that the unknown parasite encysts in the brain, nerve cord and the body cavity of E. marinus, and belongs to the Microphallidae family. An 18 month population study revealed that host abundance significantly and negatively correlated with parasite prevalence. Investigation of the trematode's influence at the transcriptomic level revealed genes with putative neurological functions, such as serotonin receptor 1A, an inebriated-like neurotransmitter, tryptophan hydroxylase and amino acid decarboxylase, present consistent altered expression in infected animals. Therefore, this study provides one of the first transcriptomic insights into the neuronal gene pathways altered in amphipods infected with a trematode parasite associated with changes to its host's behaviour and population structure. PMID- 26282622 TI - Corrosive synthesis and enhanced electromagnetic absorption properties of hollow porous Ni/SnO2 hybrids. AB - In this study, novel porous hollow Ni/SnO2 hybrids were prepared by a facile and flexible two-step approach composed of solution reduction and subsequent reaction induced acid corrosion. In our protocol, it can be found that the hydrothermal temperature exerts a vital influence on the phase crystal and morphology of Ni/SnO2 hybrids. Notably, the Ni microspheres might be completely corroded in the hydrothermal process at 220 degrees C. The complex permittivity and permeability of Ni/SnO2 hybrids-paraffin wax composite were measured based on a vector network analyzer in the frequency range of 1-18 GHz. Electromagnetic absorption properties of samples were evaluated by transmission line theory. Ni/SnO2 hybrid composites exhibit superior electromagnetic absorption properties in comparison with pristine Ni microspheres. The outstanding electromagnetic absorption performances can be observed for the hollow porous Ni/SnO2 hybrid prepared at 200 degrees C. The minimum reflection loss is -36.7 dB at 12.3 GHz, and the effective electromagnetic wave absorption band (RL < -10 dB, 90% microwave attenuation) was in the frequency range of 10.6-14.0 GHz with a thin thickness of 1.7 mm. Excellent electromagnetic absorption properties were assigned to the improved impedance match, more interfacial polarization and unique hollow porous structures, which can result in microwave multi-reflection and scattering. This novel hollow porous hybrid is an attractive candidate for new types of high performance electromagnetic wave-absorbing materials, which satisfies the current requirements of electromagnetic absorbing materials, which include wide-band absorption, high-efficiency absorption capability, thin thickness and light weight. PMID- 26282620 TI - HN-NCA heteronuclear TOCSY-NH experiment for (1)H(N) and (15)N sequential correlations in ((13)C, (15)N) labelled intrinsically disordered proteins. AB - A simple triple resonance NMR experiment that leads to the correlation of the backbone amide resonances of each amino acid residue 'i' with that of residues 'i 1' and 'i+1' in ((13)C, (15)N) labelled intrinsically disordered proteins (IDPs) is presented. The experimental scheme, {HN-NCA heteronuclear TOCSY-NH}, exploits the favourable relaxation properties of IDPs and the presence of (1) J CalphaN and (2) J CalphaN couplings to transfer the (15)N x magnetisation from amino acid residue 'i' to adjacent residues via the application of a band-selective (15)N (13)C(alpha) heteronuclear cross-polarisation sequence of ~100 ms duration. Employing non-uniform sampling in the indirect dimensions, the efficacy of the approach has been demonstrated by the acquisition of 3D HNN chemical shift correlation spectra of alpha-synuclein. The experimental performance of the RF pulse sequence has been compared with that of the conventional INEPT-based HN(CA)NH pulse scheme. As the availability of data from both the HCCNH and HNN experiments will make it possible to use the information extracted from one experiment to simplify the analysis of the data of the other and lead to a robust approach for unambiguous backbone and side-chain resonance assignments, a time saving strategy for the simultaneous collection of HCCNH and HNN data is also described. PMID- 26282623 TI - Recognition during recall failure: Semantic feature matching as a mechanism for recognition of semantic cues when recall fails. AB - Research suggests that a feature-matching process underlies cue familiarity detection when cued recall with graphemic cues fails. When a test cue (e.g., potchbork) overlaps in graphemic features with multiple unrecalled studied items (e.g., patchwork, pitchfork, pocketbook, pullcork), higher cue familiarity ratings are given during recall failure of all of the targets than when the cue overlaps in graphemic features with only one studied target and that target fails to be recalled (e.g., patchwork). The present study used semantic feature production norms (McRae et al., Behavior Research Methods, Instruments, & Computers, 37, 547-559, 2005) to examine whether the same holds true when the cues are semantic in nature (e.g., jaguar is used to cue cheetah). Indeed, test cues (e.g., cedar) that overlapped in semantic features (e.g., a_tree, has_bark, etc.) with four unretrieved studied items (e.g., birch, oak, pine, willow) received higher cue familiarity ratings during recall failure than test cues that overlapped in semantic features with only two (also unretrieved) studied items (e.g., birch, oak), which in turn received higher familiarity ratings during recall failure than cues that did not overlap in semantic features with any studied items. These findings suggest that the feature-matching theory of recognition during recall failure can accommodate recognition of semantic cues during recall failure, providing a potential mechanism for conceptually-based forms of cue recognition during target retrieval failure. They also provide converging evidence for the existence of the semantic features envisaged in feature-based models of semantic knowledge representation and for those more concretely specified by the production norms of McRae et al. (Behavior Research Methods, Instruments, & Computers, 37, 547-559, 2005). PMID- 26282624 TI - Androgen Deprivation Therapy and Secondary Hormone Therapy in the Management of Hormone-sensitive and Castration-resistant Prostate Cancer. AB - Androgen deprivation therapy (ADT) is the standard of care for patients with metastatic prostate cancer (mPC). However, nearly all patients with mPC progress to castration-resistant PC (CRPC). Arrays of treatments, including secondary hormonal therapies, are available for the treatment of mPC and CRPC, which show efficacy when administered with ADT. Continuation of ADT is recommended for CRPC treatment as therapies are added. New secondary hormonal therapies include abiraterone, targeting the CYP17 enzyme family, and enzalutamide, an androgen receptor inhibitor with heightened binding specificity. The optimal decision making process for CRPC treatment option remains unclear, pending further research and experience. PMID- 26282625 TI - Infertility, Sexual Dysfunction, and Depression: Recommendations for Future Studies. PMID- 26282626 TI - Changes in impaired self-awareness after acquired brain injury in patients following intensive neuropsychological rehabilitation. AB - The objective of this study was to investigate changes in self-awareness impairments in outpatients with acquired brain injury (ABI) and the effects these changes have on rehabilitation. Participants were 78 patients with ABI (8.3 years post-injury) who followed an intensive outpatient neuropsychological rehabilitation programme. This longitudinal study comprised pre (T1) and post (T2) measurements and a one-year follow-up (T3). Thirty-eight patients completed the study. The main outcome domains were self-awareness, depressive symptoms, psychological and physical dysfunction, and health-related quality of life (HRQoL). Patients were divided into three awareness groups: underestimation, accurate estimation, and overestimation of competencies. Most patients who underestimated their competencies at the start of treatment accurately estimated their competencies directly after treatment (9 out of 11 patients). These patients also exhibited the largest treatment effects regarding depressive symptoms, psychological and physical dysfunction, and HRQoL. Most patients with impaired self-awareness (i.e., overestimation of competencies) at the start of treatment continued to overestimate their competencies after treatment (10 out of 14 patients). These patients exhibited a significant decrease in depressive symptoms but no other treatment effects. The results indicate that changes in outcome are related to changes in awareness, which underline the importance of taking into account different awareness groups with respect to treatment effects. PMID- 26282627 TI - Where is the common ground between bone marrow mesenchymal stem/stromal cells from different donors and species? AB - Mesenchymal stem/stromal cells (MSCs) feature promising potential for cellular therapies, yet significant progress in development of MSC therapeutics and assays is hampered because of remarkable MSC heterogeneity in vivo and in vitro. This heterogeneity poses challenges for standardization of MSC characterization and potency assays as well as for MSC study comparability and manufacturing. This review discusses promising marker combinations for prospective MSC subpopulation enrichment and expansion, and reflects MSC phenotype changes due to environment and age. In order to address animal modelling in MSC biology, comparison of mouse and human MSC markers highlights current common ground of MSCs between species. PMID- 26282628 TI - Arthralgia and blood culture-negative endocarditis in middle Age Men suggest tropheryma whipplei infection: report of two cases and review of the literature. AB - BACKGROUND: Whipple's disease is a rare, often multisystemic chronic infectious disease caused by the rod-shaped bacterium Tropheryma whipplei. Very rarely the heart is involved in the process of the disease, leading to culture-negative infective endocarditis. Up to 20 % of all infective endocarditis are blood culture-negative and therefore a diagnostic challenge. We present two unusual cases of culture-negative infective endocarditis encountered in two different patients with prior history of arthralgia. A history of rheumatic arthritis or even a transient arthralgia should put Tropheryma whipplei on the top of differentials in patients of this age group presenting with culture-negative infective endocarditis, especially in cases of therapy resistance to antirheumatic agents. CASE PRESENTATION: The first patient was a 55 year-old Caucasian male with culture-negative Whipple-related adhesive pericarditis and endocarditis of the aortic valve. Importantly, the patient reported a 15-year history of therapy resistant sero-negative migratory polyarthritis. Aortic valve endocarditis developed during treatment with tocilizumab. The second patient was a 65-year-old male patient with no prior history of the classic Whipple's disease who presented with a culture-negative aortic valve endocarditis. His past medical history revealed episodes of transient arthralgia, which he was not treated for however, due to the self-limiting nature of the symptoms. Both patients underwent aortic valve replacement surgery. During surgery, pericardectomy was necessary in the first patient due to adhesive pericarditis. Post surgery both patients were started on long-term treatment with trimetoprim-sulfamethoxazol. At 1-year follow up of both patients, echocardiographic and clinical assessment revealed no signs of persistent infection. Both men reported negative history of arthralgia during the one year period post surgery. CONCLUSION: Tropheryma whipplei culture negative-infective endocarditis is an emerging clinical entity, predominantly found in middle-aged and older men with a history of arthralgia. These data highlight the need for ruling out Whipple's disease in patients with a history of arthralgia prior to initiation of biological agents in treatment of rheumatoid arthritis. There is also a need to assess for Tropheryma whipplei in all patients with culture- negative infective endocarditis. PMID- 26282629 TI - Systematic Review of Tobacco Use after Lung or Head/Neck Cancer Diagnosis: Results and Recommendations for Future Research. AB - Tobacco use after cancer diagnosis is associated with adverse cancer outcomes, yet reliable prevalence estimates for this behavior are lacking. We conducted a systematic literature review of the prevalence of current tobacco use among individuals with a history of lung or head/neck cancer (CRD #42012002625). An extensive search of electronic databases (MEDLINE, EMBASE, Cochrane Library, CINAHL, PsycINFO, and Web of Science) identified 7,777 potentially relevant articles published between 1980 and 2014 and 131 of these yielded pertinent information. Aggregating results across heterogeneous study designs and diverse patient samples, the overall mean prevalence rate of current tobacco use (mostly cigarette smoking) was 33.0% (median, 31.0%). Among current tobacco users at cancer diagnosis, the mean prevalence rate of current tobacco use (mostly cigarette smoking) was 53.8% (median, 50.3%). In many cases, an operational definition of "current" tobacco use was absent, and biochemical verification of self-reported smoking status was infrequent. These and other observed methodologic limitations in the assessment and reporting of cancer patients' tobacco use underscore the necessity of uniform tobacco use assessment in future clinical research and cancer care. PMID- 26282630 TI - Adherence to Multiple Cancer Screening Tests among Women Living in Appalachia Ohio. AB - BACKGROUND: There is a lack of information about the correlates of completing all three cancer screening tests among women living in Appalachia. METHODS: Cross sectional telephone interviews were conducted (April-September 2013) among women (n = 637) ages 51 to 75 years from 12 Appalachia Ohio counties. Outcomes of within screening guidelines were verified by medical records. Multivariable logistic regression models identified correlates of being within guidelines for all three cancer screening tests. RESULTS: Screening rates included mammography (32.1%), Pap test (36.1%), and a colorectal cancer test (30.1%). Only 8.6% of women were within guidelines for all tests. Having had a check-up in the past 2 years and having received a screening recommendation were significantly related to being within guidelines for all three tests (P < 0.01). Participants with higher annual household incomes [$60,000+; OR, 3.53; 95% confidence interval (CI), 1.49-8.33] and conditions requiring regular medical visits (OR, 3.16; 95% CI, 1.29-7.74) were more likely to be within guidelines for all three screening tests. CONCLUSION: Less than 10% of women had completed screening within guidelines for all three screening tests. Regular contact with the health care system and higher incomes were significant predictors of being within guidelines. IMPACT: Within guidelines rates for the three recommended cancer screening tests are low among women in Appalachia Ohio. This finding illustrates the need for innovative interventions to improve rates of multiple cancer screening tests. PMID- 26282632 TI - Investigation of metabolomic blood biomarkers for detection of adenocarcinoma lung cancer. AB - BACKGROUND: Untargeted metabolomics was used in case-control studies of adenocarcinoma (ADC) lung cancer to develop and test metabolite classifiers in serum and plasma as potential biomarkers for diagnosing lung cancer. METHODS: Serum and plasma were collected and used in two independent case-control studies (ADC1 and ADC2). Controls were frequency matched for gender, age, and smoking history. There were 52 adenocarcinoma cases and 31 controls in ADC1 and 43 adenocarcinoma cases and 43 controls in ADC2. Metabolomics was conducted using gas chromatography time-of-flight mass spectrometry. Differential analysis was performed on ADC1 and the top candidates (FDR < 0.05) for serum and plasma used to develop individual and multiplex classifiers that were then tested on an independent set of serum and plasma samples (ADC2). RESULTS: Aspartate provided the best accuracy (81.4%) for an individual metabolite classifier in serum, whereas pyrophosphate had the best accuracy (77.9%) in plasma when independently tested. Multiplex classifiers of either 2 or 4 serum metabolites had an accuracy of 72.7% when independently tested. For plasma, a multimetabolite classifier consisting of 8 metabolites gave an accuracy of 77.3% when independently tested. Comparison of overall diagnostic performance between the two blood matrices yielded similar performances. However, serum is most ideal given higher sensitivity for low-abundant metabolites. CONCLUSION: This study shows the potential of metabolite-based diagnostic tests for detection of lung adenocarcinoma. Further validation in a larger pool of samples is warranted. IMPACT: These biomarkers could improve early detection and diagnosis of lung cancer. PMID- 26282631 TI - Risk of Sex-Specific Cancers in Opposite-Sex and Same-Sex Twins in Denmark and Sweden. AB - BACKGROUND: Increasing evidence shows that some cancers originate in utero. It is hypothesized that elevated exposure to some steroid hormones might increase cancer risk and that hormone transfer between twin fetuses could result in different prenatal exposure to testosterone. METHODS: This large-scale prospective twin study compared opposite-sex (OS) and same-sex (SS) twins to test the impact of intrauterine exposures on cancer risk. On the basis of the Danish and Swedish twin and cancer registries, we calculated incidence rate ratios for OS and SS twins, whereas standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated for OS/SS twins compared with the general population. RESULTS: A total of 18,001 cancers were identified during 1943-2009. No significant differences were observed between OS and SS twins, neither for the sex-specific cancers nor for cancer at all sites. All-cause cancer was slightly reduced for OS and SS twins compared with the general population, significant for OS males (SIR, 0.95; 95% CI, 0.92-0.98) and for SS males and females (SIR, 0.97; 95% CI, 0.94-0.99). CONCLUSIONS: Our data suggest that having a male co-twin which may entail higher exposure to prenatal testosterone-does not increase the risk of sex-specific cancers in OS females. Furthermore, the study supports that twinning per se is not a risk factor of cancer. IMPACT: Findings are reassuring, as they fail to provide evidence for the hypothesis that endocrine or other difference in the in utero milieu affects the risk of sex-specific cancers. PMID- 26282633 TI - Probing resistivity and doping concentration of semiconductors at the nanoscale using scanning microwave microscopy. AB - We present a new method to extract resistivity and doping concentration of semiconductor materials from Scanning Microwave Microscopy (SMM) S11 reflection measurements. Using a three error parameters de-embedding workflow, the S11 raw data are converted into calibrated capacitance and resistance images where no calibration sample is required. The SMM capacitance and resistance values were measured at 18 GHz and ranged from 0 to 100 aF and from 0 to 1 MOmega, respectively. A tip-sample analytical model that includes tip radius, microwave penetration skin depth, and semiconductor depletion layer width has been applied to extract resistivity and doping concentration from the calibrated SMM resistance. The method has been tested on two doped silicon samples and in both cases the resistivity and doping concentration are in quantitative agreement with the data-sheet values over a range of 10(-3)Omega cm to 10(1)Omega cm, and 10(14) atoms per cm(3) to 10(20) atoms per cm(3), respectively. The measured dopant density values, with related uncertainties, are [1.1 +/- 0.6] * 10(18) atoms per cm(3), [2.2 +/- 0.4] * 10(17) atoms per cm(3), [4.5 +/- 0.2] * 10(16) atoms per cm(3), [4.5 +/- 1.3] * 10(15) atoms per cm(3), [4.5 +/- 1.7] * 10(14) atoms per cm(3). The method does not require sample treatment like cleavage and cross sectioning, and high contact imaging forces are not necessary, thus it is easily applicable to various semiconductor and materials science investigations. PMID- 26282634 TI - High Doses of Antimetabolites Followed by High-Dose Sequential Chemoimmunotherapy and Autologous Stem-Cell Transplantation in Patients With Systemic B-Cell Lymphoma and Secondary CNS Involvement: Final Results of a Multicenter Phase II Trial. AB - PURPOSE: Treatment of secondary CNS dissemination in patients with aggressive lymphomas remains an important, unmet clinical need. Herein, we report the final results of a multicenter phase II trial addressing a new treatment for secondary CNS lymphoma based on encouraging experiences with high doses of antimetabolites in primary CNS lymphoma and with rituximab plus high-dose sequential chemoimmunotherapy (R-HDS) in relapsed aggressive lymphoma. PATIENTS AND METHODS: HIV-negative patients with aggressive B-cell lymphoma and secondary CNS involvement at diagnosis or relapse, age 18 to 70 years, and Eastern Cooperative Oncology Group performance status <= 3 were enrolled and treated with high-doses of methotrexate and cytarabine, followed by R-HDS (cyclophosphamide, cytarabine, and etoposide) supported by autologous stem-cell transplantation (ASCT). Treatment included eight doses of rituximab and four doses of intrathecal liposomal cytarabine. The primary end point was 2-year event-free survival; the planned accrual was 38 patients. RESULTS: Thirty-eight patients were enrolled; CNS disease was detected at presentation in 16 patients. Toxicity was usually hematologic and manageable, with grade 4 febrile neutropenia in 3% of delivered courses and grade 4 nonhematologic toxicity in 2% of delivered courses. Four patients died because of toxicity. Autologous stem cells were successfully collected in 24 (89%) of 27 patients (median, 10 * 10(6)/kg); 20 patients underwent ASCT. Complete response was achieved in 24 patients (complete response rate, 63%; 95% CI, 48% to 78%). At a median follow-up of 48 months, 17 patients remained relapse free, with a 2-year event-free survival rate of 50% +/- 8%. At 5 years, 16 patients were alive, with a 5-year overall survival rate of 41% +/- 8% for the whole series and 68% +/- 11% for patients who received transplantation. Systemic (extra-CNS) and/or meningeal disease did not affect outcome. CONCLUSION: The combination of high doses of antimetabolites, R-HDS, and ASCT is feasible and effective in patients age 18 to 70 years old with secondary CNS lymphoma, and we propose it as a new standard therapeutic option. PMID- 26282636 TI - Identifying Social Distress: A Cross-Sectional Survey of Social Outcomes 12 to 36 Months After Colorectal Cancer Diagnosis. AB - PURPOSE: To establish the prevalence and determinants of poor social outcomes after a diagnosis of colorectal cancer (CRC). PATIENTS AND METHODS: All 12- to 36 month survivors of CRC (International Classification of Diseases [10th revision] codes C18 to C20) diagnosed in 2010 or 2011 and treated in the English National Health Service were identified and sent a questionnaire from their treating cancer hospital. This included the Social Difficulties Inventory, a 16-item scale of social distress (SD) comprising everyday living, money matters, and self and others subscales, plus five single items. Sociodemographic and clinical data were also collected. Analyses using descriptive statistics, chi(2) tests, and logistic regression models were conducted. RESULTS: Response rate was 63.3% (21,802 of 34,467). Of the 21,802 participants, 17,830 (81.8%) completed all SD items; 2,688 (15.1%) of these 17,830 respondents were classified as experiencing SD (everyday living, 19.5%; money matters, 15.6%; self and others, 18.1%). Multivariable analysis demonstrated having >= three long-term conditions was the strongest predictor of SD (odds ratio [OR], 6.64; 95% CI, 5.67 to 7.77 compared with no long-term conditions), followed by unemployment (OR, 5.11; 95% CI, 4.21 to 6.20 compared with being employed), having recurrent or nontreatable disease (OR, 2.75; 95% CI, 2.49 to 3.04 compared with being in remission), and having a stoma (OR, 2.10; 95% CI, 1.86 to 2.36 compared with no stoma). Additional predictors of SD were young age (< 55 years), living in a more deprived area, nonwhite ethnicity, having advanced-stage disease, having undergone radiotherapy, and being a carer. CONCLUSION: Although it is reassuring a majority do not experience social difficulties, a minority reported significant SD 12 to 36 months after diagnosis of CRC. The identified clinical and social risk factors are easy to establish and should be used to target support. PMID- 26282635 TI - Clinical Course of Oxaliplatin-Induced Neuropathy: Results From the Randomized Phase III Trial N08CB (Alliance). AB - PURPOSE: Given that the clinical course of oxaliplatin-induced neuropathy is not well defined, the current study was performed to better understand clinical parameters associated with its presentation. METHODS: Acute and chronic neuropathy was evaluated in patients receiving adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) on study N08CB (North Central Cancer Treatment Group, Alliance). Acute neuropathy was assessed by having patients complete daily questionnaires for 6 days with each cycle of FOLFOX. Before each dose of FOLFOX and as long as 18 months after chemotherapy cessation, chronic neurotoxicity was assessed with use of the 20-item, European Organisation for Research and Treatment of Cancer quality-of-life questionnaire for patients with chemotherapy induced peripheral neuropathy. RESULTS: Three hundred eight (89%) of the 346 patients had at least one symptom of acute neuropathy with the first cycle of FOLFOX; these symptoms included sensitivity to touching cold items (71%), sensitivity to swallowing cold items (71%), throat discomfort (63%), or muscle cramps (42%). Acute symptoms peaked at day 3 and improved, although they did not always resolve completely between treatments. These symptoms were about twice as severe in cycles 2 through 12 as they were in cycle 1. For chronic neurotoxicity, tingling was the most severe symptom, followed by numbness and then pain. During chemotherapy, symptoms in the hands were more prominent than they were in the feet; by 18 months, symptoms were more severe in the feet than they were in the hands. Patients with more severe acute neuropathy during the first cycle of therapy experienced more chronic sensory neurotoxicity (P < .0001). CONCLUSION: Acute oxaliplatin-induced neuropathy symptoms do not always completely resolve between treatment cycles and are only half as severe on the first cycle as compared with subsequent cycles. There is a correlation between the severities of acute and chronic neuropathies. PMID- 26282637 TI - Lymph Node Micrometastases Do Influence Breast Cancer Outcome. PMID- 26282638 TI - Complexity in the Gastric Cancer Genome and a Biomarker-Driven Trial of Poly (ADP Ribose) Polymerase Inhibition in Gastric Cancer. PMID- 26282639 TI - Immune Signature to Predict Trastuzumab Benefit: Potential and Pitfalls. PMID- 26282641 TI - Combined-Modality Therapy for Early-Stage Diffuse Large B-Cell Lymphoma: Knowing When to Quit. PMID- 26282640 TI - Effects of Music Therapy on Anesthesia Requirements and Anxiety in Women Undergoing Ambulatory Breast Surgery for Cancer Diagnosis and Treatment: A Randomized Controlled Trial. AB - PURPOSE: To investigate the effect of live and recorded perioperative music therapy on anesthesia requirements, anxiety levels, recovery time, and patient satisfaction in women experiencing surgery for diagnosis or treatment of breast cancer. PATIENTS AND METHODS: Between 2012 and 2014, 207 female patients undergoing surgery for potential or known breast cancer were randomly assigned to receive either patient-selected live music (LM) preoperatively with therapist selected recorded music intraoperatively (n=69), patient-selected recorded music (RM) preoperatively with therapist-selected recorded music intraoperatively (n=70), or usual care (UC) preoperatively with noise-blocking earmuffs intraoperatively (n=68). RESULTS: The LM and the RM groups did not differ significantly from the UC group in the amount of propofol required to reach moderate sedation. Compared with the UC group, both the LM and the RM groups had greater reductions (P<.001) in anxiety scores preoperatively (mean changes [and standard deviation: -30.9 [36.3], -26.8 [29.3], and 0.0 [22.7]), respectively. The LM and RM groups did not differ from the UC group with respect to recovery time; however, the LM group had a shorter recovery time compared with the RM group (a difference of 12.4 minutes; 95% CI, 2.2 to 22.5; P=.018). Satisfaction scores for the LM and RM groups did not differ from those of the UC group. CONCLUSION: Including music therapy as a complementary modality with cancer surgery may help manage preoperative anxiety in a way that is safe, effective, time-efficient, and enjoyable. PMID- 26282642 TI - Evaluation of the Safety and Benefit of Phase I Oncology Trials for Patients With Primary CNS Tumors. AB - PURPOSE: Patients with high-grade gliomas (HGG) are frequently excluded from first-in-human solid tumor trials because of perceived poor prognosis, excessive toxicities, concomitant drug interactions, and poor efficacy. We conducted an analysis of outcomes from select, single-agent phase I studies in patients with HGG. We compared outcomes to pooled analysis of published studies in solid tumors with various molecular and cytotoxic drugs evaluated as single agents or as combinations. PATIENT AND METHODS: Individual records of patients with recurrent HGG enrolled onto Adult Brain Tumor Consortium trials of single-agent, cytotoxic or molecular agents from 2000 to 2008 were analyzed for baseline characteristics, toxicities, responses, and survival. RESULTS: Our analysis included 327 patients with advanced, refractory HGG who were enrolled onto eight trials involving targeted molecular (n=5) and cytotoxic (n=3) therapies. At enrollment, patients had a median Karnofsky performance score of 90 and median age of 52 years; 62% were men, 63% had glioblastoma, and the median number of prior systemic chemotherapies was one. Baseline laboratory values were in an acceptable range to meet eligibility criteria. Patients were on the study for a median of two cycles (range, =3 nonhematologic and grade>=4 hematologic toxicities were 5% (28 of 565 adverse events) and 0.9% (five of 565 adverse events), respectively, and 66% of these occurred at the highest dose level. There was one death attributed to drug. Overall response rate (complete and partial response) was 5.5%. Median progression-free and overall survival times were 1.8 and 6 months, respectively. CONCLUSION: Patients with HGG who meet standard eligibility criteria may be good candidates for solid tumor phase I studies with single-agent molecular or cytotoxic drugs with favorable preclinical rationale and pharmacokinetic properties in this population. PMID- 26282645 TI - Reply to F. Tomao et al. PMID- 26282644 TI - Immune-Related Adverse Events, Need for Systemic Immunosuppression, and Effects on Survival and Time to Treatment Failure in Patients With Melanoma Treated With Ipilimumab at Memorial Sloan Kettering Cancer Center. AB - PURPOSE: Ipilimumab is a standard treatment for metastatic melanoma, but immune related adverse events (irAEs) are common and can be severe. We reviewed our large, contemporary experience with ipilimumab treatment outside of clinical trials to determine the frequency of use of systemic corticosteroid or anti-tumor necrosis factor alpha (anti-TNFalpha) therapy and the effect of these therapies on overall survival (OS) and time to treatment failure (TTF). PATIENTS AND METHODS: We reviewed retrospectively the medical records of patients with melanoma who had received treatment between April 2011 and July 2013 with ipilimumab at the standard dose of 3 mg/kg. We collected data on patient demographics, previous and subsequent treatments, number of ipilimumab doses, irAEs and how they were treated, and overall survival. RESULTS: Of the 298 patients, 254 (85%) experienced an irAE of any grade. Fifty-six patients (19%) discontinued therapy because of an irAE, most commonly diarrhea. Overall, 103 patients (35%) required systemic corticosteroid treatment for an irAE; 29 (10%) also required anti-TNFalpha therapy. Defining TTF as either starting a new treatment or death, estimated median TTF was 5.7 months. Twelve percent of patients experienced long-term disease control without receiving additional antimelanoma therapy. OS and TTF were not affected by the occurrence of irAEs or the need for systemic corticosteroids. CONCLUSION: IrAEs are common in patients treated with ipilimumab. In our experience, approximately one-third of ipilimumab treated patients required systemic corticosteroids, and almost one-third of those required further immune suppression with anti-TNFalpha therapy. Practitioners and patients should be prepared to treat irAEs and should understand that such treatment does not affect OS or TTF. PMID- 26282643 TI - Obesity, Aspirin, and Risk of Colorectal Cancer in Carriers of Hereditary Colorectal Cancer: A Prospective Investigation in the CAPP2 Study. AB - PURPOSE: In the general population, increased adiposity is a significant risk factor for colorectal cancer (CRC), but whether obesity has similar effects in those with hereditary CRC is uncertain. This prospective study investigated the association between body mass index and cancer risk in patients with Lynch syndrome (LS). PATIENTS AND METHODS: Participants with LS were recruited to the CAPP2 study, in which they were randomly assigned to receive aspirin 600 mg per day or aspirin placebo, plus resistant starch 30 g per day or starch placebo (2 * 2 factorial design). Mean intervention period was 25.0 months, and mean follow-up was 55.7 months. RESULTS: During follow-up, 55 of 937 participants developed CRC. For obese participants, CRC risk was 2.41* (95% CI, 1.22 to 4.85) greater than for underweight and normal-weight participants (reference group), and CRC risk increased by 7% for each 1-kg/m(2) increase in body mass index. The risk of all LS-related cancers in obese people was 1.77* (95% CI, 1.06 to 2.96; P = .03) greater than for the reference group. In subgroup analysis, obesity was associated with 3.72* (95% CI, 1.41 to 9.81) greater CRC risk in patients with LS with MLH1 mutation, but no excess risk was observed in those with MSH2 or MSH6 mutation (P = .5). The obesity-related excess CRC risk was confined to those randomly assigned to the aspirin placebo group (adjusted hazard ratio, 2.75; 95% CI, 1.12 to 6.79; P = .03). CONCLUSION: Obesity is associated with substantially increased CRC risk in patients with LS, but this risk is abrogated in those taking aspirin. Such patients are likely to benefit from obesity prevention and/or regular aspirin. PMID- 26282646 TI - Population-Wide Screening for Germline BRCA1 and BRCA2 Mutations: Too Much of a Good Thing? PMID- 26282647 TI - Reply to L. Antolini et al. PMID- 26282649 TI - Deeper Conversations Need Not Wait Until the End. PMID- 26282648 TI - Treatment of Brain Metastases. AB - Brain metastases (BMs) occur in 10% to 20% of adult patients with cancer, and with increased surveillance and improved systemic control, the incidence is likely to grow. Despite multimodal treatment, prognosis remains poor. Current evidence supports use of whole-brain radiation therapy when patients present with multiple BMs. However, its associated cognitive impairment is a major deterrent in patients likely to live longer than 6 months. In patients with oligometastases (one to three metastases) and even some with multiple lesions less than 3 to 4 cm, especially if the primary tumor is considered radiotherapy resistant, stereotactic radiosurgery is recommended; if the BMs are greater than 4 cm, surgical resection with or without postoperative whole-brain radiation therapy should be considered. There is increasing evidence that systemic therapy, including targeted therapy and immunotherapy, is effective against BM and may be an early choice, especially in patients with sensitive primary tumors. In patients with progressive systemic disease, limited treatment options, and poor performance status, best supportive care may be appropriate. Regardless of treatment goals, use of corticosteroids or antiepileptic medications is helpful in symptomatic patients. In this review, we provide a summary of current therapy, as well as developments in the treatment of BM from solid tumors. PMID- 26282650 TI - Randomized Phase II Trial Comparing Obinutuzumab (GA101) With Rituximab in Patients With Relapsed CD20+ Indolent B-Cell Non-Hodgkin Lymphoma: Final Analysis of the GAUSS Study. AB - PURPOSE: Obinutuzumab (GA101), a novel glycoengineered type II anti-CD20 monoclonal antibody, demonstrated responses in single-arm studies of patients with relapsed/refractory non-Hodgkin lymphoma. This is the first prospective, randomized study comparing safety and efficacy of obinutuzumab with rituximab in relapsed indolent lymphoma. The primary end point of this study was the overall response rate (ORR) in patients with follicular lymphoma after induction and safety in patients with indolent lymphoma. PATIENTS AND METHODS: A total of 175 patients with relapsed CD20(+) indolent lymphoma requiring therapy and with previous response to a rituximab-containing regimen were randomly assigned (1:1) to four once-per-week infusions of either obinutuzumab (1,000 mg) or rituximab (375 mg/m(2)). Patients without evidence of disease progression after induction therapy received obinutuzumab or rituximab maintenance therapy every 2 months for up to 2 years. RESULTS: Among patients with follicular lymphoma (n = 149), ORR seemed higher for obinutuzumab than rituximab (44.6% v 33.3%; P = .08). This observation was also demonstrated by a blinded independent review panel that measured a higher ORR for obinutuzumab (44.6% v 26.7%; P = .01). However, this difference did not translate into an improvement in progression-free survival. No new safety signals were observed for obinutuzumab, and the incidence of adverse events was balanced between arms, with the exception of infusion-related reactions and cough, which were higher in the obinutuzumab arm. CONCLUSION: Obinutuzumab demonstrated a higher ORR without appreciable differences in safety compared with rituximab. However, the clinical benefit of obinutuzumab in this setting remains unclear and should be evaluated within phase III trials. PMID- 26282652 TI - Reply to D. Przepiorka et al. PMID- 26282651 TI - Bevacizumab Combined With Weekly Paclitaxel, Pegylated Liposomal Doxorubicin, or Topotecan in Platinum-Resistant Recurrent Ovarian Cancer: Analysis by Chemotherapy Cohort of the Randomized Phase III AURELIA Trial. PMID- 26282653 TI - Acute Myeloid Leukemia Response Measures Other Than Complete Remission. PMID- 26282654 TI - Mutational Spectrum, Copy Number Changes, and Outcome: Results of a Sequencing Study of Patients With Newly Diagnosed Myeloma. AB - PURPOSE: At the molecular level, myeloma is characterized by copy number abnormalities and recurrent translocations into the immunoglobulin heavy chain locus. Novel methods, such as massively parallel sequencing, have begun to describe the pattern of tumor-acquired mutations, but their clinical relevance has yet to be established. METHODS: We performed whole-exome sequencing for 463 patients who presented with myeloma and were enrolled onto the National Cancer Research Institute Myeloma XI trial, for whom complete molecular cytogenetic and clinical outcome data were available. RESULTS: We identified 15 significantly mutated genes: IRF4, KRAS, NRAS, MAX, HIST1H1E, RB1, EGR1, TP53, TRAF3, FAM46C, DIS3, BRAF, LTB, CYLD, and FGFR3. The mutational spectrum is dominated by mutations in the RAS (43%) and nuclear factor-kappaB (17%) pathways, but although they are prognostically neutral, they could be targeted therapeutically. Mutations in CCND1 and DNA repair pathway alterations (TP53, ATM, ATR, and ZNFHX4 mutations) are associated with a negative impact on survival. In contrast, those in IRF4 and EGR1 are associated with a favorable overall survival. We combined these novel mutation risk factors with the recurrent molecular adverse features and international staging system to generate an international staging system mutation score that can identify a high-risk population of patients who experience relapse and die prematurely. CONCLUSION: We have refined our understanding of genetic events in myeloma and identified clinically relevant mutations that may be used to better stratify patients at presentation. PMID- 26282656 TI - US Food and Drug Administration Efforts to Facilitate the Use of Expanded Access Programs. PMID- 26282655 TI - Diacetylspermine Is a Novel Prediagnostic Serum Biomarker for Non-Small-Cell Lung Cancer and Has Additive Performance With Pro-Surfactant Protein B. AB - PURPOSE: We have investigated the potential of metabolomics to discover blood based biomarkers relevant to lung cancer screening and early detection. An untargeted metabolomics approach was applied to identify biomarker candidates using prediagnostic sera from the Beta-Carotene and Retinol Efficacy Trial (CARET) study. PATIENTS AND METHODS: A liquid chromatography/mass spectrometry hydrophilic interaction method designed to profile a wide range of metabolites was applied to prediagnostic serum samples from CARET participants (current or former heavy smokers), consisting of 100 patients who subsequently developed non small-cell lung cancer (NSCLC) and 199 matched controls. A separate aliquot was used to quantify levels of pro-surfactant protein B (pro-SFTPB), a previously established protein biomarker for NSCLC. On the basis of the results from the discovery set, blinded validation of a metabolite, identified as N(1),N(12) diacetylspermine (DAS), and pro-SFTPB was performed using an independent set of CARET prediagnostic sera from 108 patients with NSCLC and 216 matched controls. RESULTS: Serum DAS was elevated by 1.9-fold, demonstrating significant specificity and sensitivity in the discovery set for samples collected up to 6 months before diagnosis of NSCLC. In addition, DAS significantly complemented performance of pro-SFTPB in both the discovery and validations sets, with a combined area under the curve in the validation set of 0.808 (P < .001 v pro SFTPB). CONCLUSION: DAS is a novel serum metabolite with significant performance in prediagnostic NSCLC and has additive performance with pro-SFTPB. PMID- 26282657 TI - Results of the Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) Trial: A Behavioral Weight Loss Intervention in Overweight or Obese Breast Cancer Survivors. AB - PURPOSE: Obesity increases risk for all-cause and breast cancer mortality and comorbidities in women who have been diagnosed and treated for breast cancer. The Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) study is the largest weight loss intervention trial among survivors of breast cancer to date. METHODS: In this multicenter trial, 692 overweight/obese women who were, on average, 2 years since primary treatment for early-stage breast cancer were randomly assigned to either a group-based behavioral intervention, supplemented with telephone counseling and tailored newsletters, to support weight loss or a less intensive control intervention and observed for 2 years. Weight and blood pressure were measured at 6, 12, 18, and 24 months. Longitudinal mixed models were used to analyze change over time. RESULTS: At 12 months, mean weight loss was 6.0% of initial weight in the intervention group and 1.5% in the control group (P<.001). At 24 months, mean weight loss in the intervention and control groups was 3.7% and 1.3%, respectively (P<.001). Favorable effects of the intervention on physical activity and blood pressure were observed. The weight loss intervention was more effective among women older than 55 years than among younger women. CONCLUSION: A behavioral weight loss intervention can lead to clinically meaningful weight loss in overweight/obese survivors of breast cancer. These findings support the need to conduct additional studies to test methods that support sustained weight loss and to examine the potential benefit of intentional weight loss on breast cancer recurrence and survival. PMID- 26282658 TI - Randomized, Double-Blind Phase II Trial With Prospective Classification by ATM Protein Level to Evaluate the Efficacy and Tolerability of Olaparib Plus Paclitaxel in Patients With Recurrent or Metastatic Gastric Cancer. AB - PURPOSE: Gastric cancer cell lines, particularly those with low levels of ataxia telangiectasia mutated (ATM), a key activator of DNA damage response, are sensitive to the poly (ADP-ribose) polymerase inhibitor olaparib. We compared the efficacy of olaparib plus paclitaxel (olaparib/paclitaxel) with paclitaxel alone in patients with recurrent or metastatic gastric cancer and assessed whether low ATM expression is predictive of improved clinical outcome for olaparib/paclitaxel. PATIENTS AND METHODS: In this phase II, double-blind study (Study 39; NCT01063517), patients were randomly assigned to oral olaparib 100 mg twice per day (tablets) plus paclitaxel (80 mg/m(2) per day intravenously on days 1, 8, and 15 of every 28-day cycle) or placebo plus paclitaxel (placebo/paclitaxel), followed by maintenance monotherapy with olaparib (200 mg twice per day) or placebo. The study population was enriched to 50% for patients with low or undetectable ATM levels (ATMlow). Primary end point was progression free survival (PFS). RESULTS: One hundred twenty-three of 124 randomly assigned patients received treatment (olaparib/paclitaxel, n = 61; placebo/paclitaxel, n = 62). The screening prevalence of ATMlow patients was 14%. Olaparib/paclitaxel did not lead to a significant improvement in PFS versus placebo/paclitaxel (overall population: hazard ratio [HR], 0.80; median PFS, 3.91 v 3.55 months, respectively; ATMlow population: HR, 0.74; median PFS, 5.29 v 3.68 months, respectively). However, olaparib/paclitaxel significantly improved overall survival (OS) versus placebo/paclitaxel in both the overall population (HR, 0.56; 80% CI, 0.41 to 0.75; P = .005; median OS, 13.1 v 8.3 months, respectively) and the ATMlow population (HR, 0.35; 80% CI, 0.22 to 0.56; P = .002; median OS, not reached v 8.2 months, respectively). Olaparib/paclitaxel was generally well tolerated, with no unexpected safety findings. CONCLUSION: Olaparib/paclitaxel is active in the treatment of patients with metastatic gastric cancer, with a greater OS benefit in ATMlow patients. A phase III trial in this setting is under way. PMID- 26282660 TI - Reply to L. Wiener et al. PMID- 26282659 TI - Coffee Intake, Recurrence, and Mortality in Stage III Colon Cancer: Results From CALGB 89803 (Alliance). AB - PURPOSE: Observational studies have demonstrated increased colon cancer recurrence in states of relative hyperinsulinemia, including sedentary lifestyle, obesity, and increased dietary glycemic load. Greater coffee consumption has been associated with decreased risk of type 2 diabetes and increased insulin sensitivity. The effect of coffee on colon cancer recurrence and survival is unknown. PATIENTS AND METHODS: During and 6 months after adjuvant chemotherapy, 953 patients with stage III colon cancer prospectively reported dietary intake of caffeinated coffee, decaffeinated coffee, and nonherbal tea, as well as 128 other items. We examined the influence of coffee, nonherbal tea, and caffeine on cancer recurrence and mortality using Cox proportional hazards regression. RESULTS: Patients consuming 4 cups/d or more of total coffee experienced an adjusted hazard ratio (HR) for colon cancer recurrence or mortality of 0.58 (95% CI, 0.34 to 0.99), compared with never drinkers (Ptrend = .002). Patients consuming 4 cups/d or more of caffeinated coffee experienced significantly reduced cancer recurrence or mortality risk compared with abstainers (HR, 0.48; 95% CI, 0.25 to 0.91; Ptrend = .002), and increasing caffeine intake also conferred a significant reduction in cancer recurrence or mortality (HR, 0.66 across extreme quintiles; 95% CI, 0.47 to 0.93; Ptrend = .006). Nonherbal tea and decaffeinated coffee were not associated with patient outcome. The association of total coffee intake with improved outcomes seemed consistent across other predictors of cancer recurrence and mortality. CONCLUSION: Higher coffee intake may be associated with significantly reduced cancer recurrence and death in patients with stage III colon cancer. PMID- 26282662 TI - Is Endometrial Cancer Risk Reduced by Oral Bisphosphonate Use? PMID- 26282661 TI - Continuous Therapy Versus Fixed Duration of Therapy in Patients With Newly Diagnosed Multiple Myeloma. AB - PURPOSE: Continuous therapy (CT) prolongs progression-free survival 1 (PFS1; time from random assignment until the first progression or death), but chemotherapy resistant relapse may negatively impact overall survival (OS). Progression-free survival 2 (PFS2; time from random assignment until the second progression or death) may represent an additional tool to estimate outcome. This study evaluates the benefit of novel agent-based CT versus fixed duration of therapy (FDT) in patients with newly diagnosed myeloma. METHODS: We included patients enrolled onto three phase III trials that randomly assigned patients to novel agent-based CT versus FDT. Primary analyses were restricted to the intent-to-treat population eligible for CT (patients progression free and alive at 1 year after random assignment). Primary end points were PFS1, PFS2, and OS. All hazard ratios (HRs) and 95% CIs were adjusted for several potential confounders using Cox models. RESULTS: In the pooled analysis of the three trials, 604 patients were randomly assigned to CT and 614 were assigned to FDT. Median follow-up was 52 months. In the intent-to-treat CT population, CT (n = 417), compared with FDT (n = 410), significantly improved PFS1 (median, 32 v 16 months, respectively; HR, 0.47; 95% CI, 0.40 to 0.56; P < .001), PFS2 (median, 55 v 40 months, respectively; HR, 0.61; 95% CI, 0.50 to 0.75; P < .001), and OS (4-year OS, 69% v 60%, respectively; HR, 0.69; 95% CI, 0.54 to 0.88; P = .003). CONCLUSION: In this pooled analysis, CT significantly improved PFS1, PFS2, and OS. The improvement in PFS2 suggests that the benefit reported during first remission is not cancelled by a shorter second remission. PFS2 is a valuable end point to estimate long-term clinical benefit and should be included in future trials. PMID- 26282663 TI - Breast Density and Benign Breast Disease: Risk Assessment to Identify Women at High Risk of Breast Cancer. AB - PURPOSE: Women with proliferative breast lesions are candidates for primary prevention, but few risk models incorporate benign findings to assess breast cancer risk. We incorporated benign breast disease (BBD) diagnoses into the Breast Cancer Surveillance Consortium (BCSC) risk model, the only breast cancer risk assessment tool that uses breast density. METHODS: We developed and validated a competing-risk model using 2000 to 2010 SEER data for breast cancer incidence and 2010 vital statistics to adjust for the competing risk of death. We used Cox proportional hazards regression to estimate the relative hazards for age, race/ethnicity, family history of breast cancer, history of breast biopsy, BBD diagnoses, and breast density in the BCSC. RESULTS: We included 1,135,977 women age 35 to 74 years undergoing mammography with no history of breast cancer; 17% of the women had a prior breast biopsy. During a mean follow-up of 6.9 years, 17,908 women were diagnosed with invasive breast cancer. The BCSC BBD model slightly overpredicted risk (expected-to-observed ratio, 1.04; 95% CI, 1.03 to 1.06) and had modest discriminatory accuracy (area under the receiver operator characteristic curve, 0.665). Among women with proliferative findings, adding BBD to the model increased the proportion of women with an estimated 5-year risk of 3% or higher from 9.3% to 27.8% (P<.001). CONCLUSION: The BCSC BBD model accurately estimates women's risk for breast cancer using breast density and BBD diagnoses. Greater numbers of high-risk women eligible for primary prevention after BBD diagnosis are identified using the BCSC BBD model. PMID- 26282664 TI - Reply to P.G. Gavin et al. PMID- 26282665 TI - Advances in the Treatment of Secondary CNS Lymphoma. PMID- 26282666 TI - Experts call for smoking ban outside pubs and restaurants. PMID- 26282667 TI - The distinct role of NR2B subunit in the enhancement of visual plasticity in adulthood. AB - BACKGROUND: Experience-dependent plasticity is confined to the critical period of early postnatal life, and declines dramatically thereafter. This attenuation promotes the stabilization of cortical circuits, but also limits functional recovery of several brain diseases. The cognitive functions and synaptic plasticity in the hippocampus and prefrontal cortex are elevated following chronic magnesium treatment. Here, we explored the effect of magnesium treatment on visual plasticity and the potential clinical significance. RESULTS: Visual plasticity in adult mice was dramatically enhanced following magnesium treatment, which was concurrent with an increase in the expression of NR2 subunits of N methyl-D-aspartate receptors. Blockade of NR2B activity in both the induction and expression periods of plasticity prevented this reinstatement. However, the plasticity restored via a decrease in cortical inhibition was independent on the activation of NR2B, indicating a different underlying mechanism. The functional excitatory synapses on layer 2/3 pyramidal neurons were increased following magnesium supplementation. Moreover, the synaptic and neuronal responses were reminiscent of that within the critical period, and this rejuvenation of adult visual cortex facilitated the recovery of visual functions in amblyopia. CONCLUSIONS: Collectively, our data reveal two distinct mechanisms underlying the restoration of visual plasticity in adulthood, and the rejuvenation of adult visual cortex following magnesium treatment provides a new avenue to develop clinical therapies for adult amblyopia, as well as to explore plasticity-based treatment of other brain diseases, such as stroke and aphasia. PMID- 26282668 TI - Transverse occiput position: Using manual Rotation to aid Normal birth and improve delivery OUTcomes (TURN-OUT): A study protocol for a randomised controlled trial. AB - BACKGROUND: Fetal occiput transverse position in the form of deep transverse arrest has long been associated with caesarean section and instrumental vaginal delivery. Occiput transverse position incidentally found in the second stage of labour is also associated with operative delivery in high risk cohorts. There is evidence from cohort studies that prophylactic manual rotation reduces the caesarean section rate. This is a protocol for a double blind, multicentre, randomised, controlled clinical trial to define whether this intervention decreases the operative delivery (caesarean section, forceps or vacuum delivery) rate. METHODS/DESIGN: Eligible participants will be >=37 weeks pregnant, with a singleton pregnancy, and a cephalic presentation in the occiput transverse position on transabdominal ultrasound early in the second stage of labour. Based on a background risk of operative delivery of 49%, for a reduction to 35%, an alpha value of 0.05 and a beta value of 0.2, 416 participants will need to be enrolled. Participants will be randomised to either prophylactic manual rotation or a sham procedure. The primary outcome will be operative delivery. Secondary outcomes will be caesarean section, significant maternal mortality and morbidity, and significant perinatal mortality and morbidity. Analysis will be on an intention-to-treat basis. Primary and secondary outcomes will be compared using a chi-squared test. A logistic regression for the primary outcome will be undertaken to account for potential confounders. This study has been approved by the Ethics Review Committee (RPAH Zone) of the Sydney Local Health District, Sydney, Australia, (protocol number: X110410). DISCUSSION: This trial addresses an important clinical question concerning a commonly used procedure which has the potential to reduce operative delivery and its associated complications. Some issues discussed in the protocol include methods of assessing risk of bias due to inadequate masking of a procedural interventions, variations in intervention efficacy due to operator experience and the recruitment difficulties associated with intrapartum studies. TRIAL REGISTRATION: This trial was registered with the Australian New Zealand Clinical Trials Registry (identifier: ACTRN12613000005752 ) on 4 January 2013. PMID- 26282669 TI - Metabolic Syndrome Screening and Assertive Community Treatment: A Quality Improvement Study. AB - Metabolic syndrome defines a collection of cardiometabolic illnesses that predict risk for poor physical health and early death and is highly prevalent among those with serious mental illness. Despite recommendations for routine monitoring, those with serious mental illness frequently do not receive physical health screenings. We conducted a quality improvement (QI) project to increase rates of metabolic syndrome screening in three New York City Assertive Community Treatment (ACT) teams. The project, conducted from December 2010 to May 2011, involved educational sessions for staff and consumers and a systematic screening protocol. We collected complete metabolic syndrome screening measurements for 71% of participating ACT consumers. We found metabolic risk to be nearly universal among participants, with over half diagnosed with metabolic syndrome. We also found high rates of previously undiagnosed hypertension, diabetes, and dyslipidemia. We describe the resources and obstacles we encountered in our QI project to make systematic metabolic screening a routine part of ACT care. This QI project suggests that ACT teams can take a leadership role in screening their consumers for physical health issues, aligning with recent policy trends to better integrate behavioral health and primary care services. PMID- 26282671 TI - A Clinical Translation of the Article Titled, "The Utility of Magnetic Resonance Spectroscopy for Understanding Substance Use Disorders: A Systematic Review of the Literature". AB - BACKGROUND: While magnetic resonance spectroscopy (MRS) is a technique used in research related to substance use, MRS may be less familiar to practitioners. METHOD: This is a clinical translation of a systematic review by Hellem and Shi (this issue of JAPNA). The article provides an overview of the MRS technique and neurometabolites that are commonly studied with MRS in the human brain. The methods and results are presented for the systemic review of MRS studies among adults and focus on alcohol, methamphetamine, MDMA, cocaine, opiates/opioids, marijuana, and nicotine. RESULTS: Thirty-six studies were included in the review of literature. Substance-specific studies indicated inconsistencies with respect to alterations in brain chemistry. A consistent finding across substances (alcohol, methamphetamine, and nicotine) was the decrease of two metabolites (N acetylaspartate and choline). CONCULSION: MRS offers the possibility of identifying brain biomarkers for disease and evaluating treatment response. Needed are studies employing standardized protocols for data acquisition and reporting. PMID- 26282670 TI - The Utility of Magnetic Resonance Spectroscopy for Understanding Substance Use Disorders: A Systematic Review of the Literature. AB - The aim of this article is to present a systematic review of magnetic resonance spectroscopy (MRS) studies of substance use disorders. As a noninvasive and nonionizing imaging technique, MRS is being widely used in substance abuse research to evaluate the effects substances of abuse have on brain chemistry. Nearly 40 peer-reviewed research articles that focused on the utility of MRS in alcohol, methamphetamine, 3,4-methylenedioxymethamphetamine, cocaine, opiates, opioids, marijuana, and nicotine use disorders were reviewed. Findings indicate inconsistencies with respect to alterations in brain chemistry within each substance of abuse, and the most consistent finding across substances was decreased N-acetylaspartate and choline levels with chronic alcohol, methamphetamine, and nicotine use. Variation in the brain regions studied, imaging technique, as well as small sample sizes might explain the discrepancies in findings within each substance. Future well-designed MRS studies offer promise in examining novel treatment approaches in substance use disorders. PMID- 26282672 TI - APNA's Transitions in Practice (ATP) Certificate Program: Building and Supporting the Psychiatric Nursing Workforce. PMID- 26282673 TI - Mental Health Nurses: Are We Ready for a "Learning Health System"? PMID- 26282674 TI - Prospective evaluation of endoscopic ultrasonography-guided double-balloon occluded gastrojejunostomy bypass (EPASS) for malignant gastric outlet obstruction. PMID- 26282675 TI - MicroRNA-21 is a potential link between non-alcoholic fatty liver disease and hepatocellular carcinoma via modulation of the HBP1-p53-Srebp1c pathway. AB - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a major risk factor for hepatocellular carcinoma (HCC). However, the mechanistic pathways that link both disorders are essentially unknown. OBJECTIVE: Our study was designed to investigate the role of microRNA-21 in the pathogenesis of NAFLD and its potential involvement in HCC. METHODS: Wildtype mice maintained on a high fat diet (HFD) received tail vein injections of microRNA-21-anti-sense oligonucleotide (ASO) or miR-21 mismatched ASO for 4 or 8 weeks. Livers were collected after that time period for lipid content and gene expression analysis. Human hepatoma HepG2 cells incubated with oleate were used to study the role of miR-21 in lipogenesis and analysed with Nile-Red staining. microRNA-21 function in carcinogenesis was determined by soft-agar colony formation, cell cycle analysis and xenograft tumour assay using HepG2 cells. RESULTS: The expression of microRNA-21 was increased in the livers of HFD-treated mice and human HepG2 cells incubated with fatty acid. MicroRNA-21 knockdown in those mice and HepG2 cells impaired lipid accumulation and growth of xenograft tumour. Further studies revealed that Hbp1 was a novel target of microRNA-21 and a transcriptional activator of p53. It is well established that p53 is a tumour suppressor and an inhibitor of lipogenesis by inhibiting Srebp1c. As expected, microRNA-21 knockdown led to increased HBP1 and p53 and subsequently reduced lipogenesis and delayed G1/S transition, and the additional treatment of HBP1-siRNA antagonised the effect of microRNA-21-ASO, suggesting that HBP1 mediated the inhibitory effects of microRNA-21-ASO on both hepatic lipid accumulation and hepatocarcinogenesis. Mechanistically, microRNA-21 knockdown induced p53 transcription, which subsequently reduced expression of genes controlling lipogenesis and cell cycle transition. In contrast, the opposite result was observed with overexpression of microRNA-21, which prevented p53 transcription. CONCLUSIONS: Our findings reveal a novel mechanism by which microRNA-21, in part, promotes hepatic lipid accumulation and cancer progression by interacting with the Hbp1-p53-Srebp1c pathway and suggest the potential therapeutic value of microRNA-21-ASO for both disorders. PMID- 26282676 TI - Correspondence: Laparoscopic repair of abdominal wall hernia--"How I do it"- synopsis of a seemingly straightforward technique. AB - Abdominal wall hernia repairs are commonly performed worldwide in general surgery. There is still no agreed consensus on the optimal surgical approach. Since the turn of the twenty-first century, minimally invasive techniques have gained in popularity as they combine the advantages of limited abdominal wall dissection, reduced post-operative pain and risk of complications, and shorter hospital stay. Although the added cost incurred by using sophisticated laparoscopic instruments may be quite substantial, it is precisely counterbalanced by an improved morbidity rate, faster discharge home and time to return to work. Laparoscopic abdominal wall hernia repair is often challenging, as it requires good anatomical knowledge, eye-hand coordination and diversified laparoscopic skills. The objective of this article is not to present another set of personal data and to compare it with already published results on this matter, but simply to offer comprehensive guidelines on the practical aspects of this relatively new technique. Some of these steps have already been discussed but most of the time in a scattered way in the surgical literature, while others are the fruit of a personal expertise grasped over the years. PMID- 26282678 TI - Harmful somatic amino acid substitutions affect key pathways in cancers. AB - BACKGROUND: Cancer is characterized by the accumulation of large numbers of genetic variations and alterations of multiple biological phenomena. Cancer genomics has largely focused on the identification of such genetic alterations and the genes containing them, known as 'cancer genes'. However, the non functional somatic variations out-number functional variations and remain as a major challenge. Recurrent somatic variations are thought to be cancer drivers but they are present in only a small fraction of patients. METHODS: We performed an extensive analysis of amino acid substitutions (AASs) from 6,861 cancer samples (whole genome or exome sequences) classified into 30 cancer types and performed pathway enrichment analysis. We also studied the overlap between the cancers based on proteins containing harmful AASs and pathways affected by them. RESULTS: We found that only a fraction of AASs (39.88 %) are harmful even in known cancer genes. In addition, we found that proteins containing harmful AASs in cancers are often centrally located in protein interaction networks. Based on the proteins containing harmful AASs, we identified significantly affected pathways in 28 cancer types and indicate that proteins containing harmful AASs can affect pathways despite the frequency of AASs in them. Our cross-cancer overlap analysis showed that it would be more beneficial to identify affected pathways in cancers rather than individual genes and variations. CONCLUSION: Pathways affected by harmful AASs reveal key processes involved in cancer development. Our approach filters out the putative benign AASs thus reducing the list of cancer variations allowing reliable identification of affected pathways. The pathways identified in individual cancer and overlap between cancer types open avenues for further experimental research and for developing targeted therapies and interventions. PMID- 26282679 TI - Analysis of electron donors in photosystems in oxygenic photosynthesis by photo CIDNP MAS NMR. AB - Both photosystem I and photosystem II are considerably similar in molecular architecture but they operate at very different electrochemical potentials. The origin of the different redox properties of these RCs is not yet clear. In recent years, insight was gained into the electronic structure of photosynthetic cofactors through the application of photochemically induced dynamic nuclear polarization (photo-CIDNP) with magic-angle spinning NMR (MAS NMR). Non-Boltzmann populated nuclear spin states of the radical pair lead to strongly enhanced signal intensities that allow one to observe the solid-state photo-CIDNP effect from both photosystem I and II from isolated reaction center of spinach (Spinacia oleracea) and duckweed (Spirodela oligorrhiza) and from the intact cells of the cyanobacterium Synechocystis by (13)C and (15)N MAS NMR. This review provides an overview on the photo-CIDNP MAS NMR studies performed on PSI and PSII that provide important ingredients toward reconstruction of the electronic structures of the donors in PSI and PSII. PMID- 26282677 TI - Differential alkylation-based redox proteomics--Lessons learnt. AB - Cysteine is one of the most reactive amino acids. This is due to the electronegativity of sulphur atom in the side chain of thiolate group. It results in cysteine being present in several distinct redox forms inside the cell. Amongst these, reversible oxidations, S-nitrosylation and S-sulfenylation are crucial mediators of intracellular redox signalling, with known associations to health and disease. Study of their functionalities has intensified thanks to the development of various analytical strategies, with particular contribution from differential alkylation-based proteomics methods. Presented here is a critical evaluation of differential alkylation-based strategies for the analysis of S nitrosylation and S-sulfenylation. The aim is to assess the current status and to provide insights for future directions in the dynamically evolving field of redox proteomics. To achieve that we collected 35 original research articles published since 2010 and analysed them considering the following parameters, (i) resolution of modification site, (ii) quantitative information, including correction of modification levels by protein abundance changes and determination of modification site occupancy, (iii) throughput, including the amount of starting material required for analysis. The results of this meta-analysis are the core of this review, complemented by issues related to biological models and sample preparation in redox proteomics, including conditions for free thiol blocking and labelling of target cysteine oxoforms. PMID- 26282681 TI - Effect of cellular products of potential probiotic bacteria on the immune response of Labeo rohita and susceptibility to Aeromonas hydrophila infection. AB - In the present study, the immunological efficacy of cellular components from the potential probiotic bacteria Bacillus subtilis VSG1, Pseudomonas aeruginosa VSG2, and Lactobacillus plantarum VSG3 was evaluated in Labeo rohita fingerlings. Fish were immunized intraperitoneally with 0.1 mL phosphate-buffer solution (PBS) containing 0.1 mg of any of the following cellular components: intercellular products (ICPs) of VSG1 (BS-ICPs), heat-killed whole cell products of VSG2 (PA HKWCPs), or ICPs of VSG3 (LP-ICPs). Fish injected with 0.1 mL PBS served as the control. Various immunological parameters, including the expression of immune related genes, were measured 14 and 21 days post-immunization. The fish were challenged with Aeromonas hydrophila and mortality was recorded up to 21 days post-infection. The results revealed that administration of cellular components significantly increased the activity of serum lysozyme and the alternative complement pathway, phagocytosis, and respiratory bursts throughout the experimental period. Total serum protein, albumin, and globulin levels were significantly higher in experimental groups than in the control up to 14 days post-immunization, and decreased thereafter. With respect to immune-related genes, IL-1beta, COX-2, iNOS, and IL-10 were highly (P < 0.05) up-regulated in fish immunized with cellular components, compared to the control. The expression of TNF-alpha and NF-kappaB was up-regulated in immunized fish up to 14 days post immunization. Interestingly, fish immunized with LP-ICPs exhibited a significantly higher post-challenge relative percent survival (83.32%), followed by PA-HKWCPs (66.66%), and BS-ICPs (50%). These results indicate that cellular components of probiotic bacteria can influence immune responses, enhance disease protection, and stimulate immune-related gene expression in rohu. Hence, these cellular components may be useful as adjuvants for vaccines in aquaculture. PMID- 26282682 TI - Vitellogenin is an immunocompetent molecule for mother and offspring in fish. AB - Our understanding of the function of vitellogenin (Vg) in reproduction has undergone a transformation over the past decade in parallel with new insights into the role of Vg in immunity. Initially, Vg was regarded as a female-specific reproductive protein, which is cleaved into yolk proteins such as phosvitin (Pv) and lipovitellin (Lv), stored in egg, providing the nutrients for developing embryos. Recently, Vg is shown to be an immune-relevant molecule involved in the defense of the host against the microbes including bacterium and virus. Furthermore, Pv and Lv, that both are proteolytically cleaved products of Vg, play a defense role in developing embryos. Importantly, yolk protein-derived small peptides also display antimicrobial activity. These data together indicate that Vg, in addition to being involved in yolk protein formation, plays a non reproductive role via functioning as an immune-relevant molecule in both parent fishes and their offspring. It also shows that yolk proteins and their degraded peptides are novel players in maternal immunity, opening a new avenue to study the functions of reproductive proteins. PMID- 26282683 TI - Identification of in vitro and in vivo disconnects using transcriptomic data. AB - BACKGROUND: Integrating transcriptomic experiments within drug development is increasingly advocated for the early detection of toxicity. This is partly to reduce costs related to drug failures in the late, and expensive phases of clinical trials. Such an approach has proven useful both in the study of toxicology and carcinogenicity. However, general lack of translation of in vitro findings to in vivo systems remains one of the bottle necks in drug development. This paper proposes a method for identifying disconnected genes between in vitro and in vivo toxicogenomic rat experiments. The analytical framework is based on the joint modeling of dose-dependent in vitro and in vivo data using a fractional polynomial framework and biclustering algorithm. RESULTS: Most disconnected genes identified belonged to known pathways, such as drug metabolism and oxidative stress due to reactive metabolites, bilirubin increase, glutathion depletion and phospholipidosis. We also identified compounds that were likely to induce disconnect in gene expression between in vitro and in vivo toxicogenomic rat experiments. These compounds include: sulindac and diclofenac (both linked to liver damage), naphtyl isothiocyanate (linked to hepatoxocity), indomethacin and naproxen (linked to gastrointestinal problem and damage of intestines). CONCLUSION: The results confirmed that there are important discrepancies between in vitro and in vivo toxicogenomic experiments. However, the contribution of this paper is to provide a tool to identify genes that are disconnected between the two systems. Pathway analysis of disconnected genes may improve our understanding of uncertainties in the mechanism of actions of drug candidates in humans, especially concerning the early detection of toxicity. PMID- 26282684 TI - Fat-poor angiomyolipoma with cyst-like changes mimicking a cystic renal cell carcinoma: a case report. AB - Angiomyolipoma is a common benign renal tumor. It is typically composed of adipose tissue and hence is easily diagnosed by using imaging methods such as ultrasonography, computed tomography, and magnetic resonance imaging. However, it is difficult to differentiate an atypical angiomyolipoma such as a fat-poor angiomyolipoma from a malignant tumor by using these imaging methods. We report a case of a fat-poor angiomyolipoma with cyst-like changes in a 35-year-old man. The angiomyolipoma was initially suspected to be a cystic renal cell carcinoma according to preoperative imaging studies. A 5-cm cystic tumor with an enhanced septal wall and exophytic formation was present in the middle section of the left kidney. The patient underwent partial nephrectomy. Pathological findings showed necrosis and hematoma in almost the entire lesion, with a small amount of adipose and muscle tissue. Finally, a fat-poor angiomyolipoma was diagnosed. PMID- 26282685 TI - Internet-based information-seeking behavior for transient ischemic attack. AB - BACKGROUND: In recent years, Internet became an increasingly important tool for accessing health information and is being used more frequently to promote public health. AIMS AND/OR HYPOTHESIS: To use Google search data to explore information seeking behavior for transient ischemic attack. METHODS: We selected two groups of keywords related to transient ischemic attack: 'Transient Ischemic Attack' and 'Mini Stroke'. We obtained all available online search data performed in the United States from the Google search engine for a 10-year span--January 2004 to December 2013. The monthly and daily search data for the selected keywords were analyzed--using moving average--to explore the trends, peaks, and declining effects. RESULTS: There were three significant concurrent peaks in the Google search data for the selected keywords. Each peak was directly associated with media coverage and news headlines related to the incident of transient ischemic attack in a public figure. Following each event, it took three- to seven-days for the search trend to return to its respective average value. Furthermore, the trend was steady for 'Transient Ischemic Attack'; however, the search interest for the keyword 'Mini Stroke' shows a steady increase. The overall search interest for the selected keywords was significantly higher in the southeastern United States. CONCLUSIONS: Our study shows that changes in online search behavior can be associated with media coverage of key events (in our case transient ischemic attack) in public figures. These findings suggest that multimedia health promotion campaigns might be more effective, if increased promptly after similar media coverage. PMID- 26282686 TI - Association of Alcohol Consumption with Perception of Attractiveness in a Naturalistic Environment. AB - AIMS: To investigate the relationship between objectively-assessed alcohol consumption and perception of attractiveness in naturalistic drinking environments, and to determine the feasibility and acceptability of conducting a large-scale study in these environments. METHODS: Observational study conducted simultaneously across three public houses in Bristol, UK. Participants were required to rate the attractiveness of male and female face stimuli and landscape stimuli administered via an Android tablet computer application, after which their expired breath alcohol concentration (BrAC) was measured. RESULTS: Linear regression revealed no clear evidence for relationships between alcohol consumption and either overall perception of attractiveness for stimuli, for faces specifically, or for opposite-sex faces. The naturalistic research methodology was feasible, with high levels of participant engagement and enjoyment. CONCLUSIONS: We found no evidence for a relationship between alcohol consumption and perception of attractiveness in our large-scale naturalistic study. Our study is important given the large sample size, the successful translation of an experimental, laboratory-based paradigm to a naturalistic drinking environment and the high level of public engagement with the study. Future studies should use similarly ecologically-valid methodologies to further explore the conditions under which this effect may be observed and identify the mechanisms underlying any relationships. PMID- 26282687 TI - Immobilization of Thermomyces lanuginosus Xylanase on Aluminum Hydroxide Particles Through Adsorption: Characterization of Immobilized Enzyme. AB - Xylanase plays important roles in a broad range of industrial production as a biocatalyst, and its applications commonly require immobilization on supports to enhance its stability. Aluminum hydroxide, a carrier material with high surface area, has the advantages of simple and low-cost preparation and resistance to biodegradation, and can be potentially used as a proper support for xylanase immobilization. In this work, xylanase from Thermomyces lanuginosus was immobilized on two types of aluminum hydroxide particles (gibbsite and amorphous Al(OH)3) through adsorption, and the properties of the adsorbed enzymes were studied. Both particles had considerable adsorptive capacity and affinity for xylanase. Xylanase retained 75% and 64% of the original catalytic activities after adsorption to gibbsite and amorphous Al(OH)3. Both the adsorptions improved pH and thermal stability, lowered activation energy, and extended lifespan of the immobilized enzyme, as compared with the free enzyme. Xylanase adsorbed on gibbsite and amorphous Al(OH)3 retained 71% and 64% of its initial activity, respectively, after being recycled five times. These results indicated that aluminum hydroxides served as good supports for xylanase immobilization. Therefore, the adsorption of xylanase on aluminum hydroxide particles has promising potential for practical production. PMID- 26282688 TI - Development of Bile Salt-Resistant Leuconostoc citreum by Expression of Bile Salt Hydrolase Gene. AB - Probiotic bacteria must have not only tolerance against bile salt but also no genes for antibiotic resistance. Leuconostoc citreum is a dominant lactic acid bacterium in various fermented foods, but it is not regarded as a probiotic because it lacks bile salt resistance. Therefore, we aimed to construct a bile salt-resistant L. citreum strain by transforming it with a bile salt hydrolase gene (bsh). We obtained the 1,001 bp bsh gene from the chromosomal DNA of Lactobacillus plantarum and subcloned it into the pCB4170 vector under a constitutive P710 promoter. The resulting vector, pCB4170BSH was transformed into L. citreum CB2567 by electroporation, and bile saltresistant transformants were selected. Upon incubation with glycodeoxycholic acid sodium salt (GDCA), the L. citreum transformants grew and formed colonies, successfully transcribed the bsh gene, and expressed the BSH enzyme. The recombinant strain grew in up to 0.3% (w/v) GDCA, conditions unsuitable for the host strain. In in vitro digestion conditions of 10 mM bile salt, the transformant was over 67.6% viable, whereas only 0.8% of the host strain survived. PMID- 26282689 TI - A Liquid-Based Colorimetric Assay of Lysine Decarboxylase and Its Application to Enzymatic Assay. AB - A liquid-based colorimetric assay using a pH indicator was introduced for high throughput monitoring of lysine decarboxylase activity. The assay is based on the color change of bromocresol purple, measured at 595 nm in liquid reaction mixture, due to an increase of pH by the production of cadaverine. Bromocresol purple was selected as the indicator because it has higher sensitivity than bromothymol blue and pheonol red within a broad range and shows good linearity within the applied pH. We applied this for simple determination of lysine decarboxylase reusability using 96-well plates, and optimization of conditions for enzyme overexpression with different concentrations of IPTG on lysine decarboxylase. This assay is expected to be applied for monitoring and quantifying the liquid-based enzyme reaction in biotransformation of decarboxylase in a high-throughput way. PMID- 26282690 TI - Yeast Surface Display of Capsid Protein VP7 of Grass Carp Reovirus: Fundamental Investigation for the Development of Vaccine Against Hemorrhagic Disease. AB - VP7, an outer capsid protein of grass carp reovirus (GCRV), was expressed and displayed on the surface of Saccharomyces cerevisiae for developing an efficient vaccine against hemorrhagic disease of grass carp. The result of flow cytometry analysis indicated that protein VP7 could be displayed on the surface of yeast cells after inducing with galactose. The expression of VP7 was confirmed by western blot analysis and further visualized with confocal microscopy. The specific antibodies against VP7 generated from mice were detectable from all immune groups except the control group, which was immunized with untransformed yeast cells. The displaying VP7 on glycosylation-deficient strain EBYDeltaMnn9 was detected to induce a relatively low level of specific antibody amongst the three strains. However, the antiserum of EBYDeltaM9-VP7 showed relative high capacity to neutralize GCRV. Further neutralization testing assays indicated that the neutralizing ability of antiserum of the EBYDeltaM9-VP7 group appeared concentration dependent, and could be up to 66.7% when the antiserum was diluted to 1:50. This result indicates that appropriate gene modification of glycosylation in a yeast strain has essential effect on the immunogenicity of a yeast-based vaccine. PMID- 26282691 TI - A Double-Blind, Placebo Controlled-Trial of a Probiotic Strain Lactobacillus sakei Probio-65 for the Prevention of Canine Atopic Dermatitis. AB - Canine atopic dermatitis (CAD) is a ubiquitous, chronic inflammatory skin disorder prevalent in dogs, which results in production of abnormal levels of IgE antibodies in reciprocation to an allergen challenge. In this study, administration of the probiotic strain Lactobacillus sakei probio-65 for 2 months significantly reduced the disease severity index in experimental dogs diagnosed with CAD. In addition, one month pre-medication of L. sakei probio-65 revealed significant difference in the PVAS score in experimental dogs for both probio-65 and placebo groups. However, post 2 months treatment resulted in a significant decrease in the CASESI score values in the probio-65-treated group (p < .0.06). PMID- 26282692 TI - Characterization of a Recombinant Thermostable Arylsulfatase from Deep-Sea Bacterium Flammeovirga pacifica. AB - A novel sulfatase gene, ary423 (1,536 bp ORF), encoding a protein of 511 amino acids with a calculated molecular mass of 56 kDa, was identified from Flammeovirga pacifica, which was isolated from deep-sea sediments of west Pacific Ocean. Amino acid sequence analysis revealed that Ary423 possessed a conserved C X-A-X-R motif, which was recognized as the sulfatase signature. Phylogenetic analysis suggested that Ary423 belonged to arylsulfatases. After heterologous expression in Escherichia coli cells, the recombinant Ary423 was purified with a Ni(+) affinity column, and was shown to be highly active at a broad range of temperatures from 30 degrees to 70 degrees C, with maximum activity at 40 degrees C. Furthermore, recombinant Ary423 retained more than 70% and 40% of its maximum activity after 12 h of incubation at 50 degrees C and 60 degrees C, respectively, exhibiting good thermostability at high temperatures. The optimal pH for Ary423 was determined to be 8.0 and the activity of Ary423 could be slightly enhanced by Mg(2+). The recombinant enzyme could hydrolyze sulfate ester bonds in pnitrophenyl sulfate (NPS) and Asparagus crude polysaccharides with a specific activity of 64.8 U/mg and 25.4 U/mg, respectively. These favorable properties could make Ary423 attractive for application in the desulfating process of agar production. PMID- 26282693 TI - Correction to "Simulation of an Electrical Double Layer Model with a Low Dielectric Layer between the Electrode and the Electrolyte". PMID- 26282694 TI - Hospital-treated suicide attempts among Finnish fire setters: a follow-up study. AB - BACKGROUND: High rates of attempted and completed suicide have been reported among offenders, but there has been little attention in this respect to fire setters specifically. Aim Our aim was to investigate hospital-treated suicide attempts among male fire setters. METHODS: For each of a consecutive series of 441 pre-trial fire setters, four controls matched for age, gender and place of birth were randomly selected from the Central Population Register. Data on hospitalisation and causes of death over a 39-year period were obtained from the Finnish national registers. RESULTS: The prevalence of suicide attempts was significantly higher among fire setters than among controls. Approximately every fifth fire setter had made at least one suicide attempt which had required hospital treatment. The most common method chosen was intentional self-poisoning or exposure to noxious substances. More than 1 in 10 fire setters with at least one hospitalisation for suicide-related behaviour eventually completed suicide. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: More attention should be paid to detecting and managing suicidal behaviours among fire setters as they are a high risk group and accurate identification of their needs in this respect may not only be life-saving but also reduce recidivism. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26282695 TI - Cytokine profile of food-allergic post-liver transplant children is identified by high levels of IL-5 and low IL-10 secretion from patients' peripheral blood mononuclear cells. AB - Severe allergic reaction to food following liver transplantation is a well-known phenomenon. However, the mechanisms underlying this phenomenon are not yet elucidated. This study aimed to reveal the nature of the immune response in post transplanted allergic patients and compare them to non-allergic transplanted as well as allergic and non-allergic control subjects, with focus on cytokine milieu. Post-liver transplant patients with and without allergic reactions as well as food-allergic but otherwise healthy and healthy non-allergic control patients were recruited. We reviewed patient records and routine laboratory tests and assayed subjects' PBMCs, studying cytokine secretion profile in response to different stimuli. Post-transplant patients with food allergy showed a unique cytokine profile in response to various stimuli, with extremely elevated IL-5, low IL-10 secretion, and somewhat higher IFN-gamma. T regulatory cell number was not significantly different among the groups of patients and controls. Immune response of food-allergic post-liver transplant patients is identified by a unique cytokine profile when compared to allergic but otherwise healthy individuals. PMID- 26282696 TI - Why do patients choose (not) to participate in an exercise trial during adjuvant chemotherapy for breast cancer? AB - OBJECTIVE: Only between 25% and 50% of patients invited to participate in clinical trial-based physical exercise programs during cancer treatment agree to do so. The purpose of this study was to identify factors associated significantly with the decision (not) to participate in a randomized controlled trial of physical exercise during adjuvant chemotherapy for breast cancer. METHODS: Based on questionnaire data, we compared trial participants and non-participants on a range of sociodemographic, clinical health-related, practical, behavioral, and attitudinal variables. RESULTS: Two hundred thirty of 524 patients agreed to participate in the trial (44%). The 294 (56%) non-participants indicated that they wanted to exercise on their own or that they did not wish to exercise in the context of a trial. Those who preferred to exercise on their own were relatively similar to trial participants but were more likely to be in the maintenance exercise stage. Those non-participants who did not wish to exercise had a significantly lower level of education, were less likely to be working, reported more fatigue and lower health-related quality of life, had lower sense of self efficacy, more negative attitudes towards exercise, less social support, and perceived fewer benefits and more barriers to exercising during treatment than trial participants. CONCLUSION: Minimizing practical barriers to participation, providing educational materials on the potential benefits of exercise, and giving adequate professional and social network encouragement may increase the number of patients willing to exercise during treatment and to participate in such studies. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26282697 TI - Changes in vaginal microbiota following antimicrobial and probiotic therapy. AB - BACKGROUND: The composition of the vaginal microbiota is known to be important for health. When infections occur, antimicrobial therapy is often poorly efficacious. OBJECTIVE AND DESIGN: We used 16S rRNA gene sequencing to characterize changes in the bacterial microbiota following oral antimicrobial and probiotic interventions. RESULTS: While the bacterial vaginal profiles of women with vulvovaginal candidiasis were dominated by lactobacilli as in healthy women, and unchanged by therapy, Gardnerella vaginalis, Prevotella, Atopobium, Sneathia, and Megasphaera dominated the vagina of women with bacterial vaginosis (BV), and treatment with tinidazole plus Lactobacillus reuteri RC-14+L. rhamnosus GR-1 resulted in an increased relative abundance of indigenous L. iners or L. crispatus. CONCLUSIONS: The ability to restore homeostasis provides a rationale for conjoint use of probiotics with antibiotic treatment of BV. PMID- 26282698 TI - Indole - the scent of a healthy 'inner soil'. AB - Tryptophan is an essential amino acid with an indole nucleus. Humans cannot produce this amino acid themselves, but must obtain it through their diet. Much attention is currently paid to the wide physiological and clinical implications of the tryptophan-derived substances, serotonin and kynurenines, generated by human enzymes following the intestinal absorption of tryptophan. However, even before being absorbed, several microbial metabolites of tryptophan are formed, mainly from 'malabsorbed' (incompletely digested) proteins within the colon. The normal smell of human faeces is largely due to indole, one of the major metabolites. Recent studies indicate that this foul-smelling substance is also of utmost importance for our health. PMID- 26282699 TI - Why Prospectively Randomized Clinical Trials Have Been Rare in Reproductive Medicine and Will Remain So? AB - There is almost unanimity that modern medicine should be "evidence based." In this context, lack of prospectively randomized clinical trials (RCTs) is widely lamented in reproductive medicine. Some leading voices, indeed, increasingly suggest that only RCT-based clinical conclusions should be integrated into clinical practice, since lower levels of evidence are inadequate. We have argued that reproductive medicine requires special considerations because, like clinical oncology, fertility treatments (especially in older women) are time dependent. Unlike clinical oncology, reproductive medicine, however, does not receive substantial financial research support from government or industry and, at least in the United States, has, therefore, to be primarily funded via patient revenues. Given a 50% chance of receiving placebo, infertility patients are, understandably, reluctant to fund their own RCTs. We here selectively review this subject, contrasting opposing opinions recently published in the literature by a prominent reproductive scientist and one of the world's leading experts on evidence-based medicine. Placing these recent publications into the evolving context of infertility practice, as also addressed in this journal in recent publications, we conclude that objective reasons explain why relatively few RCTs are performed in reproductive medicine and predict that this will not change in the foreseeable future. Reproductive medicine, therefore, has to find ways to develop satisfactory clinical evidence in other ways, satisfying patients' rights to easy access to potentially beneficial medical treatments with low costs and low risks. The RCTs should be reserved for relatively high risk and/or high cost treatments. PMID- 26282700 TI - Effect of micropatterned TiO2 nanotubes thin film on the deposition of endothelial extracellular matrix: For the purpose of enhancing surface biocompatibility. AB - The vascular endothelial cells (EC) extracellular matrix (ECM) on the biomaterial surface can significantly improve the blood compatibility and cell compatibility of the cardiovascular materials. In the present study, two types of micropatterned TiO2 nanotubes surfaces (gronano and toponano) were fabricated on the titanium surface by photolithography and two-step anodizing technology, for the purpose of enhancing the deposition and loading ability of the EC ECM. The effect of the micropatterned nanotubes on EC ECM deposition and loading was investigated by qualitative and quantitative characterizations of type IV collagen (CoIV). The blood compatibility of the deposited ECM layers was evaluated by platelet adhesion and activation tests, and the endothelialization function of the deposited ECM layers was investigated by EC culture for 3 days. As a result, there was more CoIV on the toponano surface compared with the control. Meanwhile, the ECM loaded toponano (ECM/toponano) possessed better blood compatibility and better endothelialization than the control. This ECM loaded micro-/nanocomposite thin film was anticipated for the potential application of the surface modification of cardiovascular devices based on its excellent biocompatibility. PMID- 26282701 TI - Effects of the 2008 flood on economic performance and food security in Yemen: a simulation analysis. AB - Extreme weather events such as floods and droughts can have devastating consequences for individual well being and economic development, in particular in poor societies with limited availability of coping mechanisms. Combining a dynamic computable general equilibrium model of the Yemeni economy with a household-level calorie consumption simulation model, this paper assesses the economy-wide, agricultural and food security effects of the 2008 tropical storm and flash flood that hit the Hadramout and Al-Mahrah governorates. The estimation results suggest that agricultural value added, farm household incomes and rural food security deteriorated long term in the flood-affected areas. Due to economic spillover effects, significant income losses and increases in food insecurity also occurred in areas that were unaffected by flooding. This finding suggests that while most relief efforts are typically concentrated in directly affected areas, future efforts should also consider surrounding areas and indirectly affected people. PMID- 26282702 TI - Modality interactions alter the shape of acoustic mate preference functions in gray treefrogs. AB - Sexual selection takes place in complex environments where females evaluating male mating signals are confronted with stimuli from multiple sources and modalities. The pattern of expression of female preferences may be influenced by interactions between modalities, changing the shape of female preference functions, and thus ultimately altering the selective landscape acting on male signal evolution. We tested the hypothesis that the responses of female gray treefrogs, Hyla versicolor, to acoustic male advertisement calls are affected by interactions with visual stimuli. We measured preference functions for several call traits under two experimental conditions: unimodal (only acoustic signals presented), and multimodal (acoustic signals presented along with a video animated calling male). We found that females were more responsive to multimodal stimulus presentations and, compared to unimodal playbacks, had weaker preferences for temporal call characteristics. We compared the preference functions obtained in these two treatments to the distribution of male call characteristics to make inferences on the strength and direction of selection expected to act on male calls. Modality interactions have the potential to influence the course of signal evolution and thus are an important consideration in sexual selection studies. PMID- 26282705 TI - Beyond metrics? Utilizing 'soft intelligence' for healthcare quality and safety. AB - Formal metrics for monitoring the quality and safety of healthcare have a valuable role, but may not, by themselves, yield full insight into the range of fallibilities in organizations. 'Soft intelligence' is usefully understood as the processes and behaviours associated with seeking and interpreting soft data-of the kind that evade easy capture, straightforward classification and simple quantification-to produce forms of knowledge that can provide the basis for intervention. With the aim of examining current and potential practice in relation to soft intelligence, we conducted and analysed 107 in-depth qualitative interviews with senior leaders, including managers and clinicians, involved in healthcare quality and safety in the English National Health Service. We found that participants were in little doubt about the value of softer forms of data, especially for their role in revealing troubling issues that might be obscured by conventional metrics. Their struggles lay in how to access softer data and turn them into a useful form of knowing. Some of the dominant approaches they used risked replicating the limitations of hard, quantitative data. They relied on processes of aggregation and triangulation that prioritised reliability, or on instrumental use of soft data to animate the metrics. The unpredictable, untameable, spontaneous quality of soft data could be lost in efforts to systematize their collection and interpretation to render them more tractable. A more challenging but potentially rewarding approach involved processes and behaviours aimed at disrupting taken-for-granted assumptions about quality, safety, and organizational performance. This approach, which explicitly values the seeking out and the hearing of multiple voices, is consistent with conceptual frameworks of organizational sensemaking and dialogical understandings of knowledge. Using soft intelligence this way can be challenging and discomfiting, but may offer a critical defence against the complacency that can precede crisis. PMID- 26282706 TI - "So, is that your 'relative' or mine?" A political-ecological critique of census based area deprivation indices. AB - Census-based deprivation indices have been widely used in Aotearoa/New Zealand, Canada and UK to measure area-based socio-economic inequalities. This paper examines the indicators used in census-based area deprivation indices using a political ecology approach. We question whether the current indicators of deprivation derived from census data are meaningful for the all age groups and minority groups in the population, with a particular focus on deprivation indicators used in New Zealand, Canada and the United Kingdom. We comparatively reviewed methodological papers and reports that describe the indicators of deprivation in Aotearoa/New Zealand, Canada and the UK from 1975 to 2014. We consider the relationship between the notion of standards of living and measurements of deprivation and explore how hegemonic cultural constructs are implicit in measures of deprivation that privilege a Eurocentric, ageist and gender normative construction of statistics. We argue for more political ecological analyses to studying the relationship between social inequalities, geographies, health inequities and political economy to transform structures of oppression and inequality. This requires turning the analytical gaze on the wealthy and privileged instead of defaulting into deficit models to account for inequality. Studies of deprivation and inequality would benefit from understanding the processes and operations of power in the (re)production of socio-economic and health inequities to inform holistic strategies for social justice. PMID- 26282708 TI - The neoliberal diet and inequality in the United States. AB - This paper discusses increasing differentiation of U.S. dietary components by socioeconomic strata and its health implications. While upper-income groups have had increasing access to higher-quality foods, lower-to-middle-income class diets are heavily focused on "energy-dense" fares. This neoliberal diet is clearly associated with the proliferation of obesity that disproportionately affects the poor. We provide a critical review of the debate about obesity from within the critical camp in food studies, between individual-focused and structural perspectives. Using official data, we show how the US diet has evolved since the 1960s to a much greater emphasis on refined carbohydrates and vegetable oils. Inequality is demonstrated by dividing the population into households-income quintiles and how they spend on food. We then introduce our Neoliberal Diet Risk Index (NDR), comprised of measures of food-import dependency, the Gini coefficient, rates of urbanization, female labor-force participation, and economic globalization. Our index serves to measure the risk of exposure to the neoliberal diet comparatively, across time and between nations. We conclude that only a societal actor like the state can redirect the food-production system by modifying its agricultural subsidy policies. Inequality-reducing policies will make the healthier food involved in such change widely available for all. PMID- 26282709 TI - A study on knowledge, attitudes and health behaviours regarding Alzheimer's disease among community residents in Tianjin, China. AB - ACCESSIBLE SUMMARY: What is known on the subject? Several studies have measured the general public's knowledge and attitudes towards Alzheimer's disease; however, much of this work is based on western samples. Due to cultural differences, the western findings may be difficult to generalize to the Chinese general public. In addition, the few studies conducted in China were often restricted to a relatively narrow range of knowledge and attitudes. What this paper adds to existing knowledge? The general public had little knowledge of Alzheimer's disease, especially on the causes, symptoms and risk factors. In terms of attitudes, although the general public held positive attitudes towards persons with Alzheimer's disease, most of them were not sure whether or not to share a diagnosis of Alzheimer's disease with the patient. In daily life, only a low proportion of people kept mentally active. What are the implications for practice? A popularization of a wide range of knowledge about Alzheimer's disease needs to be undertaken, especially focusing on persons with low educational level and emphasizing the causes, symptoms and risk factors. Besides, there is a significant need to draw up evidence-based dietary and lifestyle guidelines for Alzheimer's disease risk reduction. Moreover, health promotion agencies should identify priority groups for Alzheimer's disease risk reduction initiatives, especially those with lower income, a lower level of knowledge on Alzheimer's disease and with chronic diseases. ABSTRACT: AIM: The purpose of this descriptive correlational cross-sectional study was to assess the current level of knowledge, attitudes and health behaviours regarding Alzheimer's disease among community residents in Tianjin, China and to identify factors related to these attributes. METHOD: A convenience sample of 140 community-dwelling adults aged 20 75 years was selected to complete a researcher-designed questionnaire about Alzheimer's disease-related knowledge, attitudes and health behaviours. RESULTS: The findings revealed that 15.7% of the participants knew the risk factors for Alzheimer's disease. With regard to attitude, 138 participants (98.6%) believed that people with Alzheimer's disease should not be discriminated against, and 55.7% were not sure whether to share a diagnosis of Alzheimer's disease with the patient. In daily life, 28.6% of the participants pursued their interests and hobbies. A lower level of health behaviours was associated with lower income, presence of chronic diseases and a lower level of knowledge about Alzheimer's disease. DISCUSSION: These findings provide a strong case for population-level risk reduction initiatives to be undertaken, especially among people with lower income, a lower level of knowledge on Alzheimer's disease and with chronic diseases. PMID- 26282707 TI - The causal effect of education on HIV stigma in Uganda: Evidence from a natural experiment. AB - RATIONALE: HIV is highly stigmatized in sub-Saharan Africa. This is an important public health problem because HIV stigma has many adverse effects that threaten to undermine efforts to control the HIV epidemic. OBJECTIVE: The implementation of a universal primary education policy in Uganda in 1997 provided us with a natural experiment to test the hypothesis that education is causally related to HIV stigma. METHODS: For this analysis, we pooled publicly available, population based data from the 2011 Uganda Demographic and Health Survey and the 2011 Uganda AIDS Indicator Survey. The primary outcomes of interest were negative attitudes toward persons with HIV, elicited using four questions about anticipated stigma and social distance. RESULTS: Standard least squares estimates suggested a statistically significant, negative association between years of schooling and HIV stigma (each P < 0.001, with t-statistics ranging from 4.9 to 14.7). We then used a natural experiment design, exploiting differences in birth cohort exposure to universal primary education as an instrumental variable. Participants who were <13 years old at the time of the policy change had 1.36 additional years of schooling compared to those who were >=13 years old. Adjusting for linear age trends before and after the discontinuity, two-stage least squares estimates suggested no statistically significant causal effect of education on HIV stigma (P-values ranged from 0.21 to 0.69). Three of the four estimated regression coefficients were positive, and in all cases the lower confidence limits convincingly excluded the possibility of large negative effect sizes. These instrumental variables estimates have a causal interpretation and were not overturned by several robustness checks. CONCLUSION: We conclude that, for young adults in Uganda, additional years of education in the formal schooling system driven by a universal primary school intervention have not had a causal effect on reducing negative attitudes toward persons with HIV. PMID- 26282710 TI - Invasive surgery reduces infarct size and preserves cardiac function in a porcine model of myocardial infarction. AB - Reperfusion injury following myocardial infarction (MI) increases infarct size (IS) and deteriorates cardiac function. Cardioprotective strategies in large animal MI models often failed in clinical trials, suggesting translational failure. Experimentally, MI is induced artificially and the effect of the experimental procedures may influence outcome and thus clinical applicability. The aim of this study was to investigate if invasive surgery, as in the common open chest MI model affects IS and cardiac function. Twenty female landrace pigs were subjected to MI by transluminal balloon occlusion. In 10 of 20 pigs, balloon occlusion was preceded by invasive surgery (medial sternotomy). After 72 hrs, pigs were subjected to echocardiography and Evans blue/triphenyl tetrazoliumchloride double staining to determine IS and area at risk. Quantification of IS showed a significant IS reduction in the open chest group compared to the closed chest group (IS versus area at risk: 50.9 +/- 5.4% versus 69.9 +/- 3.4%, P = 0.007). End systolic LV volume and LV ejection fraction measured by echocardiography at follow-up differed significantly between both groups (51 +/- 5 ml versus 65 +/- 3 ml, P = 0.033; 47.5 +/- 2.6% versus 38.8 +/- 1.2%, P = 0.005). The inflammatory response in the damaged myocardium did not differ between groups. This study indicates that invasive surgery reduces IS and preserves cardiac function in a porcine MI model. Future studies need to elucidate the effect of infarct induction technique on the efficacy of pharmacological therapies in large animal cardioprotection studies. PMID- 26282711 TI - Functional traits drive the contribution of solar radiation to leaf litter decomposition among multiple arid-zone species. AB - In arid zones, strong solar radiation has important consequences for ecosystem processes. To better understand carbon and nutrient dynamics, it is important to know the contribution of solar radiation to leaf litter decomposition of different arid-zone species. Here we investigated: (1) whether such contribution varies among plant species at given irradiance regime, (2) whether interspecific variation in such contribution correlates with interspecific variation in the decomposition rate under shade; and (3) whether this correlation can be explained by leaf traits. We conducted a factorial experiment to determine the effects of solar radiation and environmental moisture for the mass loss and the decomposition constant k-values of 13 species litters collected in Northern China. The contribution of solar radiation to leaf litter decomposition varied significantly among species. Solar radiation accelerated decomposition in particular in the species that already decompose quickly under shade. Functional traits, notably specific leaf area, might predict the interspecific variation in that contribution. Our results provide the first empirical evidence for how the effect of solar radiation on decomposition varies among multiple species. Thus, the effect of solar radiation on the carbon flux between biosphere and atmosphere may depend on the species composition of the vegetation. PMID- 26282712 TI - Physico-chemical properties, antioxidant activities and antihypertensive effects of walnut protein and its hydrolysate. AB - BACKGROUND: Some food proteins hydrolysates are found to possess multiple health effects. In this study, walnut protein (WP) was enzymatically hydrolysed by alcalase and trypsin under optimal conditions. The physico-chemical properties, antioxidant and angiotensin-converting enzyme (ACE) inhibitory activities of WP, alcalase-generated walnut protein hydrolysate (AWPH) and trypsin-generated walnut protein hydrolysate (TWPH) were comparatively studied. Stability properties of the walnut protein hydrolysate (WPH) and the antihypertensive activity in spontaneously hypertensive rats (SHRs) were also investigated. RESULTS: The WPH showed higher physico-chemical properties, antioxidant activities, ACE inhibitory activity and stability against thermal treatment and gastrointestinal digestion than WP. The results of antihypertensive effects in SHRs showed that the most potent decrease of AWPH and TWPH in the systolic blood pressure occurred at 4 h ( 26 mmHg) and 6 h (-30 mmHg) after administration. The study indicated that the WPH could significantly decrease the systolic blood pressure (P < 0.05). CONCLUSION: The WPH exhibited high physico-chemical properties, potent inhibitory activities and high stability. TWPH was more effective than AWPH in the detected properties. The results would be helpful for the comprehensive utilisation of the walnut resources. (c) 2015 Society of Chemical Industry. PMID- 26282713 TI - Tumor volume in insignificant prostate cancer: Increasing the threshold is a safe approach to reduce over-treatment. AB - BACKGROUND: There are conflicting results in the literature regarding the tumor volume (TV) threshold that defines insignificant prostate cancer (PCa). In this study, we retrospectively evaluate the association of an increasing TV with biochemical recurrence (BCR) following radical prostatectomy (RP) in order to provide further clarification surrounding the TV threshold definition for insignificant PCa. METHODS: RP patients were recruited from January 2004 to December 2009. Inclusion criteria were localized (stage <=pT2c, negative surgical margins) Gleason 6 PCa with a total TV of <=2.50 cm(3) . BCR was the primary outcome and defined as a PSA of >=0.1. All cases with BCR were re-evaluated by the pathologist with reassessment of tumor grade, pathological stage and surgical margin status. RESULTS: From 1,636 patients, 178 men (10.9%) met all inclusion criteria. Ninety-six patients (53.9%) had a TV <0.5 cm(3) and 82 patients (46.1%) had a TV 0.5-2.5 cm(3) . Three out of 178 patients (1.7%) presented with BCR during follow-up. One of these had TV <0.5 cm(3) and two had TV 0.5-2.5 cm(3) . These three cases of BCR underwent re-review of pathology; one patient was found to have a positive surgical margin and one patient was upgraded to Gleason 3 + 4 = 7. The third patient was re-reported as having positive margins for a benign hyperplastic nodule (incomplete RP specimen). Subsequently, these three cases were excluded from final analysis as they did not fit inclusion criteria. Median follow-up duration was 84 months (IQR 70-102 months). On final analysis, there were no patients with BCR, corresponding with a final BCR rate of 0% for both patients with a TV of <0.5 cm(3) and 0.5-2.5 cm(3) . CONCLUSIONS: Our results have shown that, with a median follow-up of 84 (IQR 70-102) months, patients in our cohort with localized Gleason 6 PCa with a total TV 0.5-2.5 cm(3) have a BCR rate of 0%. We would support a more liberal total TV threshold of 2.5 cm(3) for the further development of algorithms to identify patients suitable for active surveillance. PMID- 26282714 TI - Palliative head and neck radiotherapy with the RTOG 8502 regimen for incurable primary or metastatic cancers. AB - OBJECTIVES: To report on our institutional experience of palliative radiotherapy (RT) of cancers in the head and neck by the RTOG 8502 'QUAD SHOT' regimen. METHODS: Seventy-five patients completed at least 1 cycle of palliative RT to the head and neck for primary or metastatic disease based on the RTOG 8502 regimen (3.7 Gy twice daily over 2 consecutive days at 4 week intervals per cycle) between 2/2005 and 7/2014. RESULTS: Median patient age was 76 years (range 23 97). The most common histologies were squamous cell carcinoma (55%), non anaplastic thyroid carcinoma (10%) and salivary gland carcinoma (9%). Thirty patients (40%) received prior RT at the palliative site. Twenty-eight patients (37%) completed at least three RTOG 8502 cycles. Sixty-five percent of all patients had a palliative response. Median overall survival was 5.67 months (range, 0.20-34.5). Grade 3 toxicity in 4 patients (5%) consisted of acute dermatitis and functional mucositis. Palliative response was significantly correlated with increasing number of RTOG 8502 cycles (p = 0.012), but not KPS, prior RT, palliative chemotherapy, prior surgery, histology or stage. On survival analysis, palliative response (p < 0.001), KPS ? 70 (p = 0.001), and greater number of RTOG 8502 cycles (p = 0.022) remained independent predictors of improved survival. CONCLUSIONS: For patients with incurable malignant disease in the head and neck, the palliative RTOG 8502 'QUAD SHOT' regimen provides excellent rates of palliative response with minimal associated toxicity. Patients who are able to complete greater number of RT cycles have higher rates of palliative response and overall survival. PMID- 26282716 TI - Impacts of stigma on HIV risk for women who inject drugs in Java: A qualitative study. AB - BACKGROUND: People who inject drugs have experienced stigma around the world. Stigma has been found to have negative consequences for individuals in relation to health-service use, psychological wellbeing and physical health; and for populations in terms of health inequalities. Indonesia has experienced a rapid growth in injecting drug use and HIV and little is known about drivers of HIV risk among Indonesian women who inject drugs. The purpose of this paper is to describe and consider the multiple impacts of stigmatization of injecting drug use on injecting behaviors among women who inject drugs in Java. METHODS: In depth interviews were conducted with 19 women who inject drugs in Java. Mean age was 25 years, all but one was employed or at college. The interviewers were Indonesian women. RESULTS: Significant stigma around women's drug use was reported from multiple sources in Java including family, friends and health services, resulting in feelings of shame. To avoid this stigma, most of the study participants hid their drug use. They lived away from family and had few friends outside their drug-injecting circle, resulting in isolation from mainstream society and harm-reduction services. Sharing of injecting equipment was restricted to a small, closed circle of trusted friends, thus limiting possible HIV transmission to a small number of injectors. CONCLUSIONS: The stigmatization of drug use, particularly of drug use by women, in Indonesia appears to have contributed to significant shame, isolation from mainstream society and high rates of sharing injecting equipment with a small group of trusted friends (particularly the partner). PMID- 26282718 TI - Influence of MTHFR polymorphisms on cardiovascular risk markers in elite athletes. AB - OBJECTIVES: To investigate the distribution of MTHFR C677T and A1298C as well as PON1 Q192R gene polymorphisms, known to be involved in hyperhomocysteinemia related cardiovascular risk, in elite athletes. DESIGN AND METHODS: Genetic background at MTHFR and PON1 loci and plasma levels of homocysteine, folate, vitamin B12 and advanced oxidation protein product (AOPP) levels were assessed in thirty-seven 400m male hurdlers and thirty-four sedentary subjects. RESULTS: Homocysteine plasma levels and AOPPs were significantly higher in hurdlers bearing the TT677/AA1298 diplotype than in both hurdlers and sedentary subjects with other diplotypes. A positive dependence between either homocysteine or AOPP plasma levels and MTHFR, but not PON1 genotype, was observed in hurdlers. CONCLUSIONS: Elite hurdlers, having an unfavorable MTHFR genotype are exposed to increased cardiovascular risk, dependent on alterations of homocysteine and AOPP plasma levels. PMID- 26282717 TI - The sGC stimulator riociguat inhibits platelet function in washed platelets but not in whole blood. AB - BACKGROUND AND PURPOSE: Stimulation of soluble guanylyl cyclase (sGC) is a valuable therapeutic strategy for the treatment of several cardiovascular diseases. The sGC stimulator riociguat has been approved for the treatment of two forms of pulmonary hypertension. Platelets contain large amounts of sGC and play a key role in the regulation of haemostasis. Therefore, we investigated the effects of riociguat on platelet function. EXPERIMENTAL APPROACH: The effect of riociguat treatment on human platelet activation and aggregation was investigated. The sGC-specific effects of riociguat were determined by comparing wild-type and platelet-specific sGC-knockout mice. KEY RESULTS: Riociguat induced cGMP synthesis and subsequent PKG activation in human platelets, suggesting that the inhibitory effects are mediated by cGMP signalling. This finding was confirmed when sGC-knockout platelets were not inhibited by riociguat. In washed human platelets, 100 nM riociguat reduced ADP-induced GPIIb/IIIa activation, while a 10-fold higher concentration was required to reduce convulxin-stimulated GPIIb/IIIa activation. Riociguat inhibited ADP-induced platelet shape change and aggregation, while ATP-induced shape change remained unaffected. However, in PRP and whole blood, 50-100 MUM riociguat was required to inhibit platelet activation and aggregation. Riociguat in combination with iloprost significantly inhibited platelet aggregation, even in whole blood. CONCLUSIONS AND IMPLICATIONS: Riociguat inhibits platelet activation in whole blood only at concentrations above 50 MUM, while the plasma concentrations in riociguat-treated patients are 150 to 500 nM. This finding indicates that riociguat treatment does not affect platelet function in patients. Nevertheless, the possibility that riociguat acts synergistically with iloprost to inhibit platelet activation should be considered. PMID- 26282715 TI - Recommendations for the management of hepatitis C virus infection among people who inject drugs. AB - In high income countries, the majority of new and existing hepatitis C virus (HCV) infections occur among people who inject drugs (PWID). In many low and middle income countries large HCV epidemics have also emerged among PWID populations. The burden of HCV-related liver disease among PWID is increasing, but treatment uptake remains extremely low. There are a number of barriers to care which should be considered and systematically addressed, but should not exclude PWID from HCV treatment. The rapid development of interferon-free direct acting antiviral (DAA) therapy for HCV infection has brought considerable optimism to the HCV sector, with the realistic hope that therapeutic intervention will soon provide near optimal efficacy with well-tolerated, short duration, all oral regimens. Further, it has been clearly demonstrated that HCV treatment is safe and effective across a broad range of multidisciplinary healthcare settings. Given the burden of HCV-related disease among PWID, strategies to enhance HCV assessment and treatment in this group are urgently needed. These recommendations demonstrate that treatment among PWID is feasible and provide a framework for HCV assessment and care. Further research is needed to evaluate strategies to enhance testing, linkage to care, treatment, adherence, viral cure, and prevent HCV reinfection among PWID, particularly as new interferon-free DAA treatments for HCV infection become available. PMID- 26282719 TI - Daily intake and serum concentration of menaquinone-4 (MK-4) in haemodialysis patients with chronic kidney disease. AB - OBJECTIVES: Decreased concentration of menaquinone-4 (MK-4) seems to be an important risk factor of vascular calcification in haemodialysis (HD) patients. Optimal dietary intake, as well as serum MK-4 reference range, in HD has not been determined, yet. The aim of the present study was to assess daily vitamin K1 and MK-4 intakes and their relation to serum MK-4 concentration in HD patients. DESIGN AND METHODS: Daily vitamin K1 and MK-4, micro- and macronutrients and energy intakes were assessed using 3-day food diary completed by patients and serum MK-4 concentration was measured by HPLC [limit of quantification (LOQ): 0.055 ng/mL] in 85 HD patients (51 males) and 22 apparently healthy subjects. RESULTS: Daily MK-4 intake was significantly lower (by 29%) among HD, while K1 consumption was similar in both groups. Daily MK-4 intake was associated with fat and protein consumption in HD (r=0.43, p<0.001 and r=0.33, p=0.004, respectively). In HD serum MK-4 concentration was more frequently below LOQ (in 41% HD and 5% controls, p<0.001) and in those HD with quantifiable values was lower than in the controls (by 42%). The correlations between MK-4 concentrations and both MK-4 and K1 daily intakes were weaker in HD (r=0.38 and r=0.30 respectively) than in the control group (r=0.47 and r=0.45, respectively). In multiple regression analysis the variability of serum MK-4 concentrations in HD patients was explained by its daily intake. CONCLUSIONS: Decreased serum MK-4 concentration in HD patients is caused by lower dietary MK-4 intake, mainly due to diminished meat consumption, and in addition, probably reduced K1 conversion. PMID- 26282720 TI - Histamine quantification in human plasma using high resolution accurate mass LC MS technology. AB - BACKGROUND: Histamine (HA) is a small amine playing an important role in anaphylactic reactions. In order to identify and quantify HA in plasma matrix, different methods have been developed but present several disadvantages. Here, we developed an alternative method using liquid chromatography coupled with an ultra high resolution and accurate mass instrument, Q ExactiveTM (Thermo Fisher) (LCHRMS). METHODS: The method includes a protein precipitation of plasma samples spiked with HA-d4 as internal standard (IS). LC separation was performed on a C18 Accucore column (100*2.1mm, 2.6MUm) using a mobile phase containing nonafluoropentanoic acid (3nM) and acetonitrile with 0.1% (v/v) formic acid on gradient mode. Separation of analytes was obtained within 10min. Analysis was performed from full scan mode and targeted MS2 mode using a 5ppm mass window. Ion transitions monitored for targeted MS2 mode were 112.0869>95.0607m/z for HA and 116.1120>99.0855m/z for HA-d4. Calibration curves were obtained by adding standard calibration dilution at 1 to 180nM in TrisBSA. RESULTS: Elution of HA and IS occurred at 4.1min. The method was validated over a range of concentrations from 1nM to 100nM. The intra- and inter-run precisions were <15% for quality controls. Human plasma samples from 30 patients were analyzed by LCHRMS, and the results were highly correlated with those obtained using the gold standard radioimmunoassay (RIA) method. CONCLUSION: Overall, we demonstrate here that LCHRMS is a sensitive method for histamine quantification in biological human plasmas, suitable for routine use in medical laboratories. In addition, LCHRMS is less time-consuming than RIA, avoids the use of radioactivity, and could then be considered as an alternative quantitative method. PMID- 26282721 TI - New horizons in pediatric reference intervals. PMID- 26282722 TI - Reporting of a Publicly Accessible Protocol and Its Association With Positive Study Findings in Cardiovascular Trials (from the Epidemiological Study of Randomized Trials [ESORT]). AB - Selective outcome reporting is common among published randomized trials and is often associated with the reporting of positive study findings. We investigated whether publication of study protocols in publicly accessible formats is associated with the reporting of positive findings. An extended version of the Cochrane highly sensitive search strategy was used to identify reports of randomized trials on cardiovascular disease that were published in December 2012 and indexed in PubMed by November 2013. Study characteristics and methodologic characteristics were extracted in duplicate. The Fisher's exact test and multivariable logistic regression were used to compare characteristics between trials that reported a publicly accessible protocol and those that did not. One hundred ninety-one reports of cardiovascular randomized trials were identified, 23 (12%) of which reported an accessible protocol. Trials reporting an accessible protocol were significantly larger and more likely to report strong trial methods, including reporting a power calculation, attrition, and the use of an intention-to-treat analysis. Despite greater statistical power, trials reporting an accessible protocol were less likely to report positive findings after controlling for known confounders (odds ratio 0.35, 95% confidence interval 0.13 to 0.94). Reporting of an accessible protocol is associated with a reduced likelihood of reporting positive findings. Further investigation is needed to determine if this association is causal. PMID- 26282723 TI - Preoperative Electrocardiogram. PMID- 26282724 TI - Reply: To PMID 26059866. PMID- 26282725 TI - Safety and Efficacy of Staged Percutaneous Coronary Intervention During Index Admission for ST-Elevation Myocardial Infarction With Multivessel Coronary Disease (Insights from the University of Ottawa Heart Institute STEMI Registry). AB - The optimal management strategy for patients with ST-elevation myocardial infarction (STEMI) and multivessel disease has not been well established. In the present cohort study, we sought to examine the safety and efficacy of inhospital staged PCI for patients with STEMI and multivessel disease. We identified all patients with STEMI referred for primary PCI who were found to have multivessel disease (stenosis >=50% in nonculprit vessel) and compared clinical outcomes in relation to the management strategy, staged versus culprit-only PCI, for nonculprit vessel disease. The primary outcome was mortality at 180 days, and secondary outcomes included mortality during the index hospitalization and at 30 days, myocardial infarction, stent thrombosis, stroke, and bleeding. Of the 1,038 patients with STEMI meeting inclusion criteria, 259 (25%) underwent staged PCI and 779 (75%) culprit-only PCI during the index admission. Mortality at 180 days was 0.8% in patients with staged PCI and 5.0% in patients with culprit-only PCI (p = 0.003). The association between staged PCI and reduced mortality persisted after adjusting for baseline differences in patient characteristics and angiographic variables between the 2 cohorts (odds ratio 0.2, 95% confidence interval 0.04 to 0.77, p = 0.02). The rates of inhospital reinfarction in the staged and culprit-only PCI cohorts were 0.8% versus 1.3% (p = 0.50), respectively, stent thrombosis 0.8% versus 1.3% (p = 0.50), and stroke 0.4% versus 1.3% (p = 0.31). There were no inhospital adverse events related to acute occlusion of a nonculprit vessel in either cohort. Staged PCI during index admission is a safe and effective revascularization strategy for patients with STEMI and multivessel disease. PMID- 26282726 TI - Comparison of Characteristics and Outcomes of Dabigatran Versus Warfarin in Hypertensive Patients With Atrial Fibrillation (from the RE-LY Trial). AB - Hypertension is frequent in patients with atrial fibrillation (AF) and is an independent risk factor for stroke. The Randomized Evaluation of Long Term Anticoagulant TherapY (RE-LY) trial found dabigatran 110 mg (D110) and 150 mg twice daily (D150) noninferior or superior to warfarin for stroke reduction in patients with AF, with either a reduction (D110) or similar rates (D150) of major bleeding. Baseline characteristics and outcomes were compared in patients with and without hypertension. The quality of blood pressure control was also assessed. In RE-LY, 14,283 patients (78.9%) had hypertension. The mean blood pressure at baseline was 132.6 +/- 17.6/77.7 +/- 10.6 and 124.8 +/- 16.7/74.6 +/- 10.0 mm Hg for patients with and without hypertension, respectively. More patients with hypertension were diabetic (25.6% vs 14.8%, p <0.001), women (38.6% vs 28.3%, p <0.001), and had greater CHADS2 (2.3 vs 1.4, p <0.001) and CHA2DS2 VASc scores (3.8 vs 2.8, p <0.001). Mean blood pressure in all treatment arms in hypertensive patients was similar (130 +/- 18/76 +/- 11 mm Hg) during the trial. The efficacy and safety of D110 and D150 compared to warfarin were similar (p = nonsignificant) in hypertensive (stroke/systemic embolism rate of 1.47%, 1.20%, and 1.81% and major bleed rate of 2.89%, 3.70%, and 3.69% in the D110, D150, and W, respectively) and normotensive patients (stroke/systemic embolism rate of 1.79%, 0.78%, and 1.36% and major bleed rate of 2.84%, 2.37%, and 3.03% per year in the D110, D150, and W, respectively). Hypertensive patients had more major bleeds (3.39% vs 2.76%; p = 0.007). Intracranial bleeds were similar (0.47% vs 0.31%; p = 0.12). In conclusion, patients with hypertension in RE-LY were more likely female, diabetic, with a greater CHADS2 and CHA2DS2-VASc scores. Blood pressure control in RE-LY was excellent. The benefits of dabigatran over warfarin, including a substantial reduction of intracranial hemorrhage, were similar in both hypertensive and non-hypertensive patients. PMID- 26282727 TI - Using Natriuretic Peptides for Selection of Patients in Acute Heart Failure Clinical Trials. AB - Acute heart failure (AHF) is a complex syndrome with presentations ranging from hypotensive cardiogenic shock to hypertensive emergency with pulmonary edema. Most patients with AHF present with worsening of chronic HF signs and symptoms over days to weeks, and significant heterogeneity exists. It can, therefore, be challenging to characterize the overall population. The complexity of defining the AHF phenotype has been cited as a contributing cause for neutral results in most pharmacologic trials in patients with AHF. Dyspnea has been a routine inclusion criterion for AHF for over a decade, but the utility of current instruments for dyspnea assessment has been called into question. Furthermore, the threshold of clinical severity that prompts patient admission of an HF clinic visit may vary substantially across regions in global trials. Therefore, the inclusion of cardiac-specific biomarkers has been incorporated into AHF trials as 1 strategy to support inclusion of the target patient population and potentially enrich the population with patients at risk for clinical outcomes. In conclusion, we discuss strategies to support appropriate patient selection in AHF trials with an emphasis on using biomarker criteria that may improve the likelihood of success with future AHF clinical trials. PMID- 26282728 TI - Smac-Derived Aza-Peptide As an Aminopeptidase-Resistant XIAP BIR3 Antagonist. AB - The peptidic nature of anti-IAPs N-terminus Smac-derived peptides precludes their utilization as potential therapeutic anticancer agents. Recent advances in the development of novel Smacderived peptidomimetics and non-peptidic molecules with improved anti-IAPs activity and resistance to proteolytic cleavage have been reported and led to a number of candidates that are currently in clinical trials including LCL-161, SM-406/AT-406, GDC-0512/GDC-0917, and birinapant. As an attempt to improve the proteolytic stability of Smac peptides, we developed the Aza-peptide AzaAla- Val-Pro-Phe-Tyr-NH2 (2). Unlike unmodified peptide Ala-Val Pro-Phe-Tyr-NH2 (1), analogue (2) exhibited resistance towards proteolytic cleavage by two aminopeptidases; LAP and DPP-IV, while retaining its IAP inhibitory activity. This was due to the altered planar geometry of the P1 residue side chain. Our findings showed that using aza-isosteres of bioactive peptide sequences imbue the residue with imperviousness to proteolysis; underscoring a potential approach for developing a new generation of Smac-derived Aza-peptidomimetics. PMID- 26282729 TI - Expression, Purification and Immunological Characterization of Recombinant Shiga Toxin A Subunit. AB - Shiga toxin family comprises toxins belonging to two major groups, Stx1 and Stx2, produced by the bacteria Shigella dysenteriae and some strains of Escherichia coli. Shiga toxins are the leading cause of diarrhea associated with life threatening hemolytic uremic syndrome (HUS). StxA is a ribosome inactivating protein (RIP) which inhibits the protein synthesis in most species of prokaryotes and eukaryotes. An in vitro expression system has not been reported to produce full-length biological active StxA subunit; hence substantial progress has been hampered. In the present study, a DNA fragment (955 bp Gene Bank Accn No HM017965) encoding for subunit A of Stx was amplified from Shigella dysenteriae type 1 and subsequently cloned in pGEX-5X-2 vector. We successfully produced recombinant StxA as GST fusion protein in Escherichia coli using pGEX-5X-2-STXA construct under IPTG induction. For the purpose of immunization the GST-tag was removed by factor Xa mediated endoproteolytic cleavage from GST-StxA. Antisera raised against rStxA in mice reacted with recombinant purified protein of rStxA and lysate of Shiga toxin. It was shown that antisera produced against rStxA significantly recognized Stx producing strains of S. dysenteriae and E. coli. The antiserum produced effectively neutralized the Shiga toxin's cytotoxicity towards Vero cells. PMID- 26282730 TI - Adhesive curing through low-voltage activation. AB - Instant curing adhesives typically fall within three categories, being activated by either light (photocuring), heat (thermocuring) or chemical means. These curing strategies limit applications to specific substrates and can only be activated under certain conditions. Here we present the development of an instant curing adhesive through low-voltage activation. The electrocuring adhesive is synthesized by grafting carbene precursors on polyamidoamine dendrimers and dissolving in aqueous solvents to form viscous gels. The electrocuring adhesives are activated at -2 V versus Ag/AgCl, allowing tunable crosslinking within the dendrimer matrix and on both electrode surfaces. As the applied voltage discontinued, crosslinking immediately terminated. Thus, crosslinking initiation and propagation are observed to be voltage and time dependent, enabling tuning of both material properties and adhesive strength. The electrocuring adhesive has immediate implications in manufacturing and development of implantable bioadhesives. PMID- 26282731 TI - Efficacy and tolerability of canagliflozin as add-on to metformin in the treatment of type 2 diabetes mellitus: a meta-analysis. AB - PURPOSE: The aim of this study is to assess the efficacy and tolerability of canagliflozin, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, added on to metformin in patients with type 2 diabetes mellitus (T2DM). METHODS: Literatures were searched from major electronic databases, as well as the Chinese State Food and Drug Administration and clinicaltrials.gov for unpublished studies. Only randomized controlled trials (RCTs) comparing canagliflozin with placebo in combination with metformin were included. Two reviewers independently selected studies, evaluated the risk of bias, and extracted data. The included RCTs were analyzed by the software RevMan 5.3 provided by the Cochrane Collaboration. RESULTS: Six RCTs were chosen for the meta-analysis. Compared to placebo, canagliflozin produced absolute reduction in glycated hemoglobin A1c (HbA1c) ( 0.66% [-0.72%, -0.61%]). The proportion of patients who achieved target HbA1c was significantly greater in the canagliflozin-treated group (1.86 [1.69, 2.03]). Canagliflozin led to greater fasting plasma glucose (FPG) reduction of 1.49 mmol/L (100 mg/day) and 1.80 mmol/L (300 mg/day). Significant body weight loss of 2.09% (100 mg/day) and 2.66% (300 mg/day) with canagliflozin was observed. Canagliflozin was found to improve beta cell function in terms of homeostasis model assessment (HOMA2-%B) (15.59% [12.84%, 18.35%]). Higher incidences of genital mycotic infection/female and pollakiuria (increased urine frequency) were noted with canagliflozin compared with placebo-controlled groups. CONCLUSIONS: Canagliflozin is a potential option as an add-on to metformin based on its improvement in HbA1c, FPG, body weight, and beta cell function, but further studies are demanded to strengthen this evidence. Common adverse events (AEs) like genital mycotic infection/female and pollakiuria were identified. PMID- 26282732 TI - Sustaining dry surfaces under water. AB - Rough surfaces immersed under water remain practically dry if the liquid-solid contact is on roughness peaks, while the roughness valleys are filled with gas. Mechanisms that prevent water from invading the valleys are well studied. However, to remain practically dry under water, additional mechanisms need consideration. This is because trapped gas (e.g. air) in the roughness valleys can dissolve into the water pool, leading to invasion. Additionally, water vapor can also occupy the roughness valleys of immersed surfaces. If water vapor condenses, that too leads to invasion. These effects have not been investigated, and are critically important to maintain surfaces dry under water. In this work, we identify the critical roughness scale, below which it is possible to sustain the vapor phase of water and/or trapped gases in roughness valleys - thus keeping the immersed surface dry. Theoretical predictions are consistent with molecular dynamics simulations and experiments. PMID- 26282733 TI - Associations between metabolic dysregulation and circulating biomarkers of fibrosis: the Cardiovascular Health Study. AB - AIM: Fibrosis is one postulated pathway by which diabetes produces cardiac and other systemic complications. Our aim was to determine which metabolic parameters are associated with circulating fibrosis-related biomarkers transforming growth factor-beta (TGF-beta) and procollagen type III N-terminal propeptide (PIIINP). METHODS: We used linear regression to determine the cross-sectional associations of diverse metabolic parameters, including fasting glucose, fasting insulin, body mass index, fatty acid binding protein 4, and non-esterified fatty acids, with circulating levels of TGF-beta (n = 1559) and PIIINP (n = 3024) among community living older adults in the Cardiovascular Health Study. RESULTS: Among the main metabolic parameters we examined, only fasting glucose was associated with TGF beta (P = 0.03). In contrast, multiple metabolic parameters were associated with PIIINP, including fasting insulin, body mass index, and non-esterified fatty acids (P<0.001, P<0.001, P=0.001, respectively). These associations remained statistically significant after mutual adjustment, except the association between BMI and PIIINP. CONCLUSIONS: Isolated hyperglycemia is associated with higher serum concentrations of TGF-beta, while a broader phenotype of insulin resistance is associated with higher serum PIIINP. Whether simultaneous pharmacologic targeting of these two metabolic phenotypes can synergistically reduce the risk of cardiac and other manifestations of fibrosis remains to be determined. PMID- 26282735 TI - Prophylactic Use of Tranexamic Acid for Postpartum Bleeding Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. AB - Despite multimodal approaches to treatment, postpartum hemorrhage (PPH) is a life threatening condition whose incidence continues to rise. In developing areas, such as sub-Saharan Africa, PPH is the leading cause of maternal mortality. Tranexamic acid (TXA) is a possible prophylactic treatment for the prevention of PPH. We performed a systematic review and meta-analysis of randomized trials comparing prophylactic TXA vs placebo or no treatment in term parturients to quantify the effects of prophylactic TXA administration on peripartum bleeding outcomes. The meta-analysis was performed using a random-effects model. The outcomes assessed were (i) incidence of PPH, (ii) mean blood loss (in milliliters) within 24hours, (iii) incidence of red blood cell transfusion within 24hours, (iv) use of additional uterotonics, (v) minor side effects (ie, nausea, vomiting, headache, etc), (vi) major venous thromboembolism, (vii) length of hospital stay, and (viii) mortality. Eighteen trials (3846 subjects) were included in the quantitative analysis, with 1935 patients receiving TXA. The studies were of poor to moderate quality. Prophylactic TXA administration was associated with a decreased incidence of PPH after delivery (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.17-0.59; P = .0006), a reduction in mean blood loss by 149.1mL (95% CI, 112.9-185.2; P < .00001), and a reduction in red blood cell transfusions (OR, 0.28; 95% CI, 0.15-0.49; P < .00001) while also being associated with a reduction in the use of additional uterotonics (OR, 0.45; 95% CI, 0.30-0.66; P < .00001). Minor side effects were more common in those who received TXA (OR, 2.51; 95% CI, 1.69-3.74; P < .00001). There appeared to be no increased risk of venous thromboembolism and no difference in length of hospital stay associated with TXA use. Although prophylactic TXA administration may be associated with improved peripartum bleeding, existing evidence is insufficient for any definitive recommendations secondary to the poor to moderate quality of the literature. A large well-designed, methodologically sound, randomized controlled trial is needed to better delineate the true effect size and address potential safety concerns. PMID- 26282734 TI - Sonographical parameters of the finger pulley system in healthy adults. AB - INTRODUCTION: To establish normative values of tendon to bone distances (TBDs) to evaluate the A2 and A4 annular pulley integrity, we hypothesized that these values correlate with gender, athletic exercise, occupation, individual's age and body height. METHODS: Ultrasonography of 200 healthy individuals was performed prospectively. TBDs for the A2 and A4 pulley sections were measured for all fingers. Evaluation was performed in resting position and active forced flexion. Examination parameters included gender, age, body height, occupation, athletic exercise level, and hand dominance. Assessment of resting position and active forced flexion was done. RESULTS: No clinically relevant differences of TBDs with respect to the aforementioned parameters were observed. But TBDs were significantly greater in active forced flexion than in resting position for all measured pulley sections. Intraobserver reliability was very satisfactory. CONCLUSIONS: Establishing normative values will help to detect injured pulleys more precisely and examination should be performed both in resting position and active forced flexion. PMID- 26282736 TI - Adoptive Immunotherapies After Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Hematologic Malignancies. AB - Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for patients with chemotherapy-resistant hematologic malignancies that are usually fatal in absence of treatment. Hematopoietic stem cell transplantation is associated with significant early and late morbidity and mortality. Graft-versus host disease, infections, and relapse are the most important causes of mortality after HSCT. Until now, these complications have been managed mainly with pharmacological drugs, but in some situations, this approach clearly shows its limit. As such, there is a significant need for novel therapies for the treatment of complications after allogeneic HSCT. In this review, the currently available adoptive immunotherapies offering an alternative in case of treatment failure of HSCT complications will be described. The results of the main clinical trials based on immune cell infusion will be discussed and the strategies aiming at maximizing cytotoxic T-lymphocyte, regulatory T-cell, natural killer cell, cytokine-induced killer cell, and gammadelta T-cell efficacies in the context of immunotherapy approaches after allogeneic HSCT in patients with hematologic malignancies will be gathered. PMID- 26282737 TI - The influence of environmental factors on protistan microorganisms in grassland soils along a land-use gradient. AB - In this study, we investigated the effect of land use intensity, soil parameters and vegetation on protistan communities in grassland soils. We performed qualitative (T-RFLP) and quantitative (qPCR) analyses using primers specifically targeting the 18S rRNA gene for all Eukarya and for two common flagellate groups, i.e. the Chrysophyceae and the Kinetoplastea. Both approaches were applied to extracted soil DNA and RNA, in order to distinguish between the potentially active protists (i.e. RNA pool) and the total protistan communities, including potentially inactive and encysted cells (i.e. DNA pool). Several environmental determinants such as site, soil parameters and vegetation had an impact on the T RFLP community profiles and the abundance of the quantified 18S rRNA genes. Correlating factors often differed between quantitative (qPCR) and qualitative (T RFLP) approaches. For instance the Chrysophyceae/Eukarya 18S rDNA ratio as determined by qPCR correlated with the C/N ratio, whereas the community composition based on T-RLFP analysis was not affected indicating that both methods taken together provide a more complete picture of the parameters driving protist diversity. Moreover, distinct T-RFs were obtained, which could serve as potential indicators for either active organisms or environmental conditions like water content. While site was the main determinant across all investigated exploratories, land use seemed to be of minor importance for structuring protist communities. The impact of other parameters differed between the target groups, e.g. Kinetoplastea reacted on changes to water content on all sites, whereas Chrysophyceae were only affected in the Schorfheide. Finally, in most cases different responses were observed on RNA- and DNA-level, respectively. Vegetation for instance influenced the two flagellate groups only at the DNA-level across all sites. Future studies should thus include different protistan groups and also distinguish between active and inactive cells, in order to reveal causal shifts in community composition and abundance in agriculturally used systems. PMID- 26282738 TI - Low biosorption of PVA coated engineered magnetic nanoparticles in granular sludge assessed by magnetic susceptibility. AB - When engineered nanoparticles (ENP) enter into wastewater treatment plants (WWTP) their removal from the water phase is driven by the interactions with the biomass in the biological treatment step. While studies focus on the interactions with activated flocculent sludge, investigations on the detailed distribution of ENP in other types of biomass, such as granulated sludge, are needed to assess their potential environmental pollution. This study employed engineered magnetic nanoparticles (EMNP) coated with polyvinyl alcohol (PVA) as model nanoparticles to trace their fate in granular sludge from WWT. For the first time, magnetic susceptibility was used as a simple approach for the in-situ quantification of EMNP with a high precision (error <2%). Compared to other analytical methods, the magnetic susceptibility requires no sample preparation and enabled direct quantification of EMNP in both the aqueous phase and the granular sludge. In batch experiments granular sludge was exposed to EMNP suspensions for 18 h. The results revealed that the removal of EMNP from the water phase (5-35%) and biosorption in the granular sludge were rather low. Less than 2.4% of the initially added EMNP were associated with the biomass. Loosely bounded to the granular sludge, desorption of EMNP occurred. Consequently, the removal of EMNP was mainly driven by physical co-sedimentation with the biomass instead of sorption processes. A mass balance elucidated that the majority of EMNP were stabilized by particulate organic matter in the water phase and can therefore likely be transported further. The magnetic susceptibility enabled tracing EMNP in complex matrices and thus improves the understanding of the general distribution of ENP in technical as well as environmental systems. PMID- 26282739 TI - Assessment of occupational exposure to BTEX compounds at a bus diesel-refueling bay: A case study in Johannesburg, South Africa. AB - Of increasing concern is pollution by volatile organic compounds, with particular reference to five aromatic hydrocarbons (benzene, toluene, ethyl benzene and two isomeric xylenes; BTEX). These pollutants are classified as hazardous air pollutants. Due to the potential health risks associated with these pollutants, BTEX concentrations were monitored at a bus diesel-refueling bay, in Johannesburg, South Africa, using gas chromatography, coupled with a photo ionization detector. Results indicate that o-xylene (29-50%) and benzene (13-33%) were found to be the most abundant species of total BTEX at the site. Benzene was within South African occupational limits, but above international occupational exposure limits. On the other hand, occupational concentrations of toluene, ethyl benzene and xylenes were within national and international occupational limits throughout the monitoring period, based on 8-hour workday weighted averages. Ethyl-benzene and p-xylene concentrations, during winter, correspond to activity at the site, and thus idling of buses during refueling may elevate results. Overall, occupational air quality at the refueling bay is a matter of health concern, especially with regards to benzene exposure, and future reduction strategies are crucial. Discrepancies between national and international limit values merit further investigation to determine whether South African guidelines for benzene are sufficiently precautionary. PMID- 26282740 TI - The role of direct photolysis and indirect photochemistry in the environmental fate of ethylhexyl methoxy cinnamate (EHMC) in surface waters. AB - The aquatic environmental fate of ethylhexyl methoxy cinnamate (EHMC), one of the most used UVB filters worldwide, was studied by assessing its environmental persistence and photoinduced transformations. The role of direct and indirect photolysis was evaluated. Direct photolysis was shown to play a key role, and this process is expected to be the main attenuation route of EHMC in sunlit surface waters. In contrast, the reaction with OH radicals would be negligible and that with (3)CDOM* would at most be a secondary process. The measurement of the quantum yield of direct photolysis and of the rate constants of reaction with photogenerated transient species (or, sometimes, the use of reasonable values for the latter) allowed the prediction of the EHMC half-life time in surface waters, by means of a validated photochemical model. The predicted EHMC lifetime is of the order of hours to a few days in fair-weather summertime, and the main factors controlling the EHMC phototransformation in sunlit surface waters would be the water depth and the dissolved organic carbon (DOC) content. The formation of transformation products (TPs) was followed as well via HPLC/HRMS. Three TPs were detected in the samples exposed to UVA radiation, while one additional TP was detected in the samples exposed to UVB radiation. The detected TPs comprised 4 methoxybenzaldehyde, a hydroxylated derivative and dimeric species. Through the use of heterogeneous photocatalysis with TiO2, seven additional TPs were identified, most of them resulting from the further degradation of primary TPs formed through direct photolysis and that might be detected in aquatic systems as well. The photodegradation of EHMC in the presence of TiO2 yielded more toxic TPs than the parent compound (as determined with the Vibrio fischeri Microtox assay). The increased toxicity is partially accounted for by the formation of 4 methoxybenzaldehyde. PMID- 26282742 TI - Abiotic reversible self-assembly of fulvic and humic acid aggregates in low electrolytic conductivity solutions by dynamic light scattering and zeta potential investigation. AB - The aggregation of humic substances and their interaction with filtration media (membranes, soils) has implications for our understanding of membrane fouling during water treatment, the facilitated transport of contaminants, and the transport of organic matter through the microbial loop. To investigate the aggregation of fulvic and humic acids in low electrolytic conductivity solutions, laboratory studies of simulated environmental water samples as well as actual environmental water samples were examined. Intensity-, volume-, and number-based particle size distributions (PSDs) were obtained by dynamic light scattering. Aggregates were categorized into three ranges, i.e., 10-100 nm, 100-1000 nm, and >1 MUm. Individual biomacromolecules and the aggregates between 10 nm and 1 MUm were presumed to be precursors for the formation of a large 5-MUm-sized-particle. The self-assembly of the large-in-volume, few-in-number, 5-MUm-sized particle was observed in real-time and occurred in unfiltered samples and in samples filtered (0.45 MUm) at a nominal size one order of magnitude smaller. The supramicrometer sized particle formed, dissipated, and spontaneously re-formed over turbulent/quiescent cycles in the presence of sodium azide indicating reversible abiotic self-assembly. Zeta potential analyses demonstrated that colloidal stability increased as concentration increased. DLS studies of the environmental water samples were comparable to those of the simulated laboratory samples. The operational range of the instrumentation used in these experiments was 0.6 nm-6 MUm; therefore, aggregates larger than 6 MUm may exist in these solutions. PMID- 26282741 TI - Pesticide impact on aquatic invertebrates identified with Chemcatcher(r) passive samplers and the SPEAR(pesticides) index. AB - Pesticides negatively affect biodiversity and ecosystem function in aquatic environments. In the present study, we investigated the effects of pesticides on stream macroinvertebrates at 19 sites in a rural area dominated by forest cover and arable land in Central Germany. Pesticide exposure was quantified with Chemcatcher(r) passive samplers equipped with a diffusion-limiting membrane. Ecological effects on macroinvertebrate communities and on the ecosystem function detritus breakdown were identified using the indicator system SPEARpesticides and the leaf litter degradation rates, respectively. A decrease in the abundance of pesticide-vulnerable taxa and a reduction in leaf litter decomposition rates were observed at sites contaminated with the banned insecticide Carbofuran (Toxic Units>=-2.8), confirming the effect thresholds from previous studies. The results show that Chemcatcher(r) passive samplers with a diffusion-limiting membrane reliably detect ecologically relevant pesticide pollution, and we suggest Chemcatcher(r) passive samplers and SPEARpesticides as a promising combination to assess pesticide exposure and effects in rivers and streams. PMID- 26282744 TI - Regional Risk Assessment for climate change impacts on coastal aquifers. AB - Coastal aquifers have been identified as particularly vulnerable to impacts on water quantity and quality due to the high density of socio-economic activities and human assets in coastal regions and to the projected rising sea levels, contributing to the process of saltwater intrusion. This paper proposes a Regional Risk Assessment (RRA) methodology integrated with a chain of numerical models to evaluate potential climate change-related impacts on coastal aquifers and linked natural and human systems (i.e., wells, river, agricultural areas, lakes, forests and semi-natural environments). The RRA methodology employs Multi Criteria Decision Analysis methods and Geographic Information Systems functionalities to integrate heterogeneous spatial data on hazard, susceptibility and risk for saltwater intrusion and groundwater level variation. The proposed approach was applied on the Esino River basin (Italy) using future climate hazard scenarios based on a chain of climate, hydrological, hydraulic and groundwater system models running at different spatial scales. Models were forced with the IPCC SRES A1B emission scenario for the period 2071-2100 over four seasons (i.e., winter, spring, summer and autumn). Results indicate that in future seasons, climate change will cause few impacts on the lower Esino River valley. Groundwater level decrease will have limited effects: agricultural areas, forests and semi-natural environments will be at risk only in a region close to the coastline which covers less than 5% of the total surface of the considered receptors; less than 3.5% of the wells will be exposed in the worst scenario. Saltwater intrusion impact in future scenarios will be restricted to a narrow region close to the coastline (only few hundred meters), and thus it is expected to have very limited effects on the Esino coastal aquifer with no consequences on the considered natural and human systems. PMID- 26282743 TI - The influence of nitrogen fertiliser rate and crop rotation on soil methane flux in rain-fed potato fields in Wuchuan County, China. AB - As one of the important greenhouse gases, the characteristics and principles of methane exchange characteristics in cultivated lands have become hot topics in current climate change research. This study examines the influences of nitrogen fertilisation, temperature and soil water content on methane exchange characteristic and methane exchange functional gene-pmoA gene abundance based on experimental observations of methane exchange fluxes using the static chamber-gas chromatographic method and measurements of methanotroph gene copy numbers in three growing periods by real-time PCR in rain-fed potato fields. The results indicate that the rain-fed potato fields were a CH4 sink with an average annual methane absorption (negative emission) of 940.8+/-103.2 g CH4-C/ha/year. The cumulative methane absorption first exhibited flat and subsequently increasing trend with the increase of nitrogen fertilisation from 0~135 kg N.ha(-1). Methane cumulative absorption significantly increased with the increase of temperature when temperatures were below 19.6 degrees C. Methane oxidation capacity (methanotroph pmoA gene copy numbers) showed an increasing and subsequently decreasing trend with the increase of soil moisture. Crop rotation was observed to increase the methane absorption in rain-fed potato fields and nearly one time higher than that under continuous cropping. A mechanism concept model of the methane exchange in rain-fed potato fields was advanced in this paper. PMID- 26282745 TI - Consequences of phosphate application on glyphosate uptake by roots: Impacts for environmental management practices. AB - Phosphate (PO4(3-)) fertilization is a common practice in agricultural fields also targets for glyphosate application. Due to their chemical similarities, PO4(3-) and glyphosate compete for soil adsorbing sites, with PO4(3-) fertilization increasing glyphosate bioavailability in the soil solution. After PO4(3-) fertilization, its concentration will be elevated in the soil solution and both PO4(3-) and glyphosate will be readily available for runoff into aquatic ecosystems. In this context, man-made riparian buffer strips (RBS) at the interface of agricultural lands and waterways can be used as a green technology to mitigate water contamination. The plants used in RBS form a barrier to agricultural wastes that can limit runoff, and the ability of these plants to take up these compounds through their roots plays an important role in RBS efficacy. However, the implications of PO4(3-) for glyphosate uptake by roots are not yet clearly demonstrated. Here, we addressed this problem by hydroponically cultivating willow plants in nutrient solutions amended with glyphosate and different concentrations of PO4(3-), assuring full availability of both chemicals to the roots. Using a phosphate carrier inhibitor (phosphonophormic acid-PFA), we found that part of the glyphosate uptake is mediated by PO4(3-) transporters. We observed, however, that PO4(3-) increased glyphosate uptake by roots, an effect that was related to increased root cell membrane stability. Our results indicate that PO4(3-) has an important role in glyphosate physiological effects. Under agricultural conditions, PO4(3-) fertilization can amplify glyphosate efficiency by increasing its uptake by the roots of undesired plants. On the other hand, since simultaneous phosphate and glyphosate runoffs are common, non-target species found near agricultural fields can be affected. PMID- 26282746 TI - Seepage patterns of Diuron in a ditch bed during a sequence of flood events. AB - Although ditches limit surface water contamination, groundwater recharge through ditches in Mediterranean catchments may result in groundwater contamination. We analysed the dynamics of pesticide percolation in ditches by conducting an original lab experiment that mimicked the successive percolation processes that occur during a flood season. Nine successive percolation events were operated on an undisturbed soil column collected from a ditch bed. The infiltrating water was doped with (14)C-Diuron at concentrations that were chosen to decrease between the events so as to correspond to values observed during actual flood events. The water and solute fluxes were monitored during each event, and the final extractable and non-extractable Diuron residues in the column were determined. Two main observations were made. First, a high leaching potential was observed through the ditch bed over a succession of infiltrating flood events, with 58.9% of the infiltrated Diuron and its metabolites leaching. Second, compared with the contamination of surface water circulating in the ditches, the contamination of seepage water exhibited smaller peak values and persisted much longer because of the desorption of Diuron residues stored in the ditch bed. Thus, ditches serve as buffering zones between surface and groundwater. However, compared with field plots, ditches appear to be a preferential location for the percolation of pesticides into groundwater at the catchment scale. PMID- 26282747 TI - Tracing dissolved organic matter (DOM) from land-based aquaculture systems in North Patagonian streams. AB - Chile is the second largest producer of salmonids worldwide. The first step in the production of salmonids takes place in land-based aquacultures. However, the effects of the discharge from these aquacultures on stream dissolved organic matter (DOM) content, molecular composition and degradability are unknown. The aim of this study was thus to investigate the inputs of anthropogenic DOM from land-based aquaculture to the predominantly pristine river systems of North Patagonia. We hypothesized, that i) DOM exported from land-based aquaculture mainly consists of protein-like fluorescence (tyrosine and tryptophan) released from fish feces and food remains, and that ii) this DOM is highly degradable and therefore rapidly turned-over within the receiving streams. In the North Patagonian region we conducted a screening of ten land-based aquacultures and an intensive sampling campaign for one aquaculture. This was combined with longitudinal transects and a degradation experiment in order to couple the composition of DOM exported from land-based aquacultures to its degradability in streams. We measured dissolved organic carbon (DOC) concentration by high temperature catalytic oxidation and DOM composition by fluorescence spectroscopy and parallel factor analysis. In the effluent of the ten screened aquacultures and in the repeated sampling of one aquaculture, we consistently found an increase of DOC concentrations and a dominance of protein-like fluorescence. The protein-like fluorescence rapidly disappeared downstream of the aquacultures, and in the degradation experiment. 21% of the DOC export from the repeatedly sampled aquaculture resulted from food addition and 76% from fish production. We conclude that large amounts of degradable DOM are exported from land-based aquacultures. This probably has strong effects on the ecological structure and function of North Patagonian streams, and similarly affected streams worldwide. PMID- 26282748 TI - Habitat and water quality variables as predictors of community composition in an Indonesian coral reef: a multi-taxon study in the Spermonde Archipelago. AB - Assemblages of corals, sponges, foraminifera, sediment bacteria and sediment archaea were assessed at two depths in the Spermonde Archipelago. Our goal was to assess to what extent variation in composition could be explained by habitat and water quality variables. The habitat variables consisted of depth, substrate type and scleractinian coral cover while water quality variables were derived from ocean color satellite imagery, including the colored dissolved organic matter index (CDOM), chlorophyll-a (Chlor-a) and remote sensing reflectance at 645n m (Rrs_645). Together, habitat and water quality variables explained from 31% (sediment bacteria) to 80% (forams) of the variation in composition. The variation in composition of corals, sponges, forams and sediment archaea was primarily related to habitat variables, while the variation in composition of sediment bacteria was primarily related to water quality variables. Habitat and water quality variables explained similar amounts of variation in the composition of corals and sediment bacteria. CDOM (sponges, sediment bacteria and sediment archaea), Chlor-a (corals and forams) and Rrs_645 (sponges and forams) proved significant predictors of variation in composition for the studied taxa. In addition to water quality variables, all taxa responded to a range of habitat variables including depth and the percentage cover of various benthic life forms including coral cover variables, rubble and sand. Sand cover was the most important habitat variable for corals, sponges, sediment bacteria and sediment archaea. Coral life forms including the cover of branching and tabular corals were important habitat variables for sponges and forams. These results show marked differences in how various taxa respond to variation in habitat and water quality in the Spermonde Archipelago. Moreover, our results indicate that variables estimated from ocean color satellite imagery proved to be better predictors of variation in marine community composition than commonly-used proxies such as the distance offshore or distance to the nearest river. PMID- 26282749 TI - The importance of humin in soil characterisation: A study on Amazonian soils using different fluorescence techniques. AB - Soil organic matter (SOM) is a complex mixture of molecules with different physicochemical properties, with humic substances (HS) being the main component as it represents around 20-50% of SOM structure. Soil of the Amazon region is considered one of the larger carbon pools of the world; thus, studies of the humic fractions are important for understanding the dynamics of organic matter (OM) in these soils. The aim of this study was to use laser-induced fluorescence spectroscopy (LIFS) and a combination of excitation-emission matrix (EEM) fluorescence with Parallel Factor Analysis (CP/PARAFAC) to assess the characteristics of humin (HU) extracted from Amazonian soils. The results obtained using LIFS showed that there was an increasing gradient of humification degree with depth, the deeper horizon presenting a higher amount of aromatic groups in the structure of HU. From the EEM, the contribution of two fluorophores with similar behaviour in the structures of HU and whole soil was assessed. Additionally, the results showed that the HU fraction might represent a larger fraction of SOM than previously thought: about 80-93% of some Amazon soils. Therefore, HU is an important humic fraction, thus indicating its role in environmental analysis, mainly in soil analysis. PMID- 26282750 TI - Uptake and toxicity of Cd, Cu and Pb mixtures in the isopod Asellus aquaticus from waterborne exposure. AB - The present study evaluated interactions of waterborne Cd, Cu and Pb mixtures on metal uptake rates in the isopod Asellus aquaticus and related this to mixture effects on toxicity. Secondly, it was assessed whether observed mixture effects were better related to isopod body concentrations compared to exposure concentrations. Isopods were exposed for 10 days to single, binary and tertiary mixtures including five different concentrations of Cd (0.107 to 277 MUg L(-1)), Cu (3.35 to 2117 MUg L(-1)) and Pb (0.782 to 443 MUg L(-1)). Mortality was assessed every day while isopod body concentrations, growth (biomass) and energy reserves (glycogen, lipid and protein reserves) were assessed at the end of the experiment. Synergistic interactions of combined Cd and Pb exposure on Cd and Pb uptake as well as on growth rates and mortality rates were observed. Mixture effects of combined Cd and Pb exposure on toxicity endpoints were directly related to increased Cd uptake in the Cd+Pb treatment. No mixture interactions of Cu on Cd or Pb uptake (and vice versa), nor on toxicity endpoints were observed. All toxicity endpoints were related to body concentrations. However, mixture effects disappeared when growth and mortality rates were expressed on body concentrations instead of exposure concentrations. By combining information of mixture effects on metal uptake with mixture toxicity data, the present study provides more insight in the way metal mixtures interfere with aquatic organisms and how they can induce toxic effects. PMID- 26282751 TI - Pharmaceutical load in sewage sludge and biochar produced by hydrothermal carbonization. AB - We investigated the removal of twelve pharmaceuticals in sewage sludge by hydrothermal carbonization (HTC), which has emerged as a technology for improving the quality of organic waste materials producing a valuable biochar material. In this study, the HTC converted sewage sludge samples to a biochar product within 4h at a temperature of 210 degrees C and a resulting pressure of about 15 bar. Initial pharmaceutical load of the sewage sludge was investigated as well as the residual concentrations in biochar produced from spiked and eight native sewage sludge samples from three waste water treatment plants. Additionally, the solid contents of source material and product were compared, which showed a considerable increase of the solid content after filtration by HTC. All pharmaceuticals except sulfamethoxazole, which remained below the limit of quantification, frequently occurred in the investigated sewage sludges in the MUg/kg dry matter (DM) range. Diclofenac, carbamazepine, metoprolol and propranolol were detected in all sludge samples with a maximum concentration of 800 MUg/kgDM for metoprolol. HTC was investigated regarding its contaminant removal efficiency using spiked sewage sludge. Pharmaceutical concentrations were reduced for seven compounds by 39% (metoprolol) to>=97% (carbamazepine). In native biochar samples the four compounds phenazone, carbamazepine, metoprolol and propranolol were detected, which confirmed that the HTC process can reduce the load of micropollutants. In contrast to the other investigated compounds phenazone concentration increased, which was further addressed in thermal behaviour studies including three structurally similar potential precursors. PMID- 26282752 TI - Pesticide runoff from energy crops: A threat to aquatic invertebrates? AB - The European Union aims to reach a 10% share of biofuels in the transport sector by 2020. The major burden is most likely to fall on already established annual energy crops such as rapeseed and cereals for the production of biodiesel and bioethanol, respectively. Annual energy crops are typically cultivated in intensive agricultural production systems, which require the application of pesticides. Agricultural pesticides can have adverse effects on aquatic invertebrates in adjacent streams. We assessed the relative ecological risk to aquatic invertebrates associated with the chemical pest management from six energy crops (maize, potato, sugar beet, winter barley, winter rapeseed, and winter wheat) as well as from mixed cultivation scenarios. The pesticide exposure related to energy crops and cultivation scenarios was estimated as surface runoff for 253 small stream sites in Central Germany using a GIS-based runoff potential model. The ecological risk for aquatic invertebrates, an important organism group for the functioning of stream ecosystems, was assessed using acute toxicity data (48-h LC50 values) of the crustacean Daphnia magna. We calculated the Ecological Risk from potential Pesticide Runoff (ERPR) for all three main groups of pesticides (herbicides, fungicides, and insecticides). Our findings suggest that the crops potato, sugar beet, and rapeseed pose a higher ecological risk to aquatic invertebrates than maize, barley, and wheat. As maize had by far the lowest ERPR values, from the perspective of pesticide pollution, its cultivation as substrate for the production of the gaseous biofuel biomethane may be preferable compared to the production of, for example, biodiesel from rapeseed. PMID- 26282753 TI - In vitro evaluation of oestrogenic/androgenic activity of the serum organochlorine pesticide mixtures previously described in a breast cancer case control study. AB - Some organochlorine pesticides (OCs) have been individually linked to breast cancer (BC) because they exert oestrogenic effects on mammary cells. However, humans are environmentally exposed to more or less complex mixtures of these organochlorines, and the biological effects of these mixtures must be elucidated. In this work we evaluated the in vitro effects exerted on human BC cells by the OC mixtures that were most frequently detected in two groups of women who participated in a BC case-control study developed in Spain: healthy women and women diagnosed with BC. The cytotoxicity, oestrogenicity, and androgenicity of the most prevalent OC mixtures found in healthy women (H-mixture) and in BC patients (BC-mixture) were tested at concentrations that resembled those found in the serum of the evaluated women. Our results showed that both OC mixtures presented a similar oestrogenic activity and effect on cell viability, but BC mixture showed an additional anti-androgenic effect. These results indicate that although the proliferative effect exerted by these mixtures on human breast cells seems to depend mainly on their oestrogenic action, the BC-mixture might additionally induce cell proliferation due to its anti-androgenic activity, therefore increasing the carcinogenic potential of this mixture. The findings of this study demonstrate that subtle variations in the composition of a mixture may induce relevant changes in its biological action. PMID- 26282754 TI - Tracing dissolved organic carbon and trihalomethane formation potential between source water and finished drinking water at a lowland and an upland UK catchment. AB - Rising dissolved organic carbon (DOC) concentrations in many upland UK catchments represents a challenge for drinking water companies, in particular due to the role of DOC as a precursor in the formation of trihalomethanes (THMs). Whereas traditionally, the response of drinking water companies has been focussed on treatment processes, increasingly, efforts have been made to better understanding the role of land use and catchment processes in affecting drinking water quality. In this study, water quality, including DOC and THM formation potential (THMFP) was assessed between the water source and finished drinking water at an upland and a lowland catchment. Surprisingly, the lowland catchment showed much higher reservoir DOC concentrations apparently due to the influence of a fen within the catchment from where a major reservoir inflow stream originated. Seasonal variations in water quality were observed, driving changes in THMFP. However, the reservoirs in both catchments appeared to dampen these temporal fluctuations. Treatment process applied in the 2 catchments were adapted to reservoir water quality with much higher DOC and THMFP removal rates observed at the lowland water treatment works where coagulation-flocculation was applied. However, selectivity during this DOC removal stage also appeared to increase the proportion of brominated THMs produced. PMID- 26282755 TI - Litter chemistry prevails over litter consumers in mediating effects of past steel industry activities on leaf litter decomposition. AB - Soil pollution has adverse effects on the performance and life history traits of microorganisms, plants, and animals, yet evidence indicates that even the most polluted sites can support structurally-complex and dynamic ecosystems. The present study aims at determining whether and how litter decomposition, one of the most important soil ecological processes leaf, is affected in a highly trace metal polluted site. We postulated that past steel mill activities resulting in soil pollution and associated changes in soil characteristics would influence the rate of litter decomposition through two non-exclusive pathways: altered litter chemistry and responses of decomposers to lethal and sub-lethal toxic stress. We carried out a litter-bag experiment using Populus tremula L. leaf litter collected at, and allowed to decompose in, a trace metal polluted site and in three unpolluted sites used as controls. We designed a fully-factorial transplant experimental design to assess effects of litter origin and exposure site on the rate of litter decomposition. We further determined initial litter chemistry, fungal biomass, mesofauna abundance in litter bags, and the soil macrofauna community. Irrespective of the site of litter exposure, litter originating from the polluted site had a two-fold faster decomposition than litter from the unpolluted sites. Litter chemistry, notably the lignin content, seemed most important in explaining the degradation rate of the leaf litter. Abundance of meso and macro-detritivores was higher at the polluted site than at the unpolluted sites. However, litter decomposition proceeded at similar rates in polluted and unpolluted sites. Our results show that trace metal pollution and associated soil and litter changes do not necessarily weaken consumer control on litter decomposition through lethal and sub-lethal toxic stress. PMID- 26282756 TI - Getting water right: A case study in water yield modelling based on precipitation data. AB - Water yield is a key ecosystem service in river basins and especially in dry regions around the World. In this study we carry out a modelling analysis of water yields in the Chubut River basin, located in one of the driest districts of Patagonia, Argentina. We focus on the uncertainty around precipitation data, a driver of paramount importance for water yield. The objectives of this study are to: i) explore the spatial and numeric differences among six widely used global precipitation datasets for this region, ii) test them against data from independent ground stations, and iii) explore the effects of precipitation data uncertainty on simulations of water yield. The simulations were performed using the ecosystem services model InVEST (Integrated Valuation of Ecosystem Services and Tradeoffs) with each of the six different precipitation datasets as input. Our results show marked differences among datasets for the Chubut watershed region, both in the magnitude of precipitations and their spatial arrangement. Five of the precipitation databases overestimate the precipitation over the basin by 50% or more, particularly over the more humid western range. Meanwhile, the remaining dataset (Tropical Rainfall Measuring Mission - TRMM), based on satellite measurements, adjusts well to the observed rainfall in different stations throughout the watershed and provides a better representation of the precipitation gradient characteristic of the rain shadow of the Andes. The observed differences among datasets in the representation of the rainfall gradient translate into large differences in water yield simulations. Errors in precipitation of +30% (-30%) amplify to water yield errors ranging from 50 to 150% (-45 to -60%) in some sub-basins. These results highlight the importance of assessing uncertainties in main input data when quantifying and mapping ecosystem services with biophysical models and cautions about the undisputed use of global environmental datasets. PMID- 26282757 TI - Toxicity decrease in urban wastewaters treated by a new biofiltration process. AB - We carried out a project aimed to evaluate the possible role played by the freshwater zebra mussel (Dreissena polymorpha) in the possible decrease of some environmental pollutants recalcitrant to tradition wastewater treatments. By the help of a pilot-plant built in the largest wastewater treatment plant of Milan (Italy), we tested several waste mixtures in order to measure the chemicals' abatement made by mussels' biofiltration. This study represents the last step of the wider project and it aimed to evaluate if the decrease in the concentration of some urban pollutants measured in wastewaters was followed by a corresponding toxicity reduction. Thus, we performed 7-day exposures under laboratory conditions to test the toxicity of the raw wastewaters and those preliminary filtered by zebra mussels, through the measurement of different end-points of acute and chronic toxicity. Results showed a clear positive effect of mussels' biofiltration mainly to decrease the acute toxicity made by the two tested wastewater mixtures, while the biomarkers' suite used to evaluate the chronic toxicity showed contradictory results. PMID- 26282758 TI - Wastewater treatment by a modular, domestic-scale reedbed system for safe horticultural irrigation. AB - The aim of the study was to assess the sequential treatment performance of a commercial, domestic-scale modular reedbed system intended to provide safe horticultural irrigation water. Previously only mechanical treatment systems involving forced aeration with subsequent disinfection, usually by tablet chlorination, had been accredited in Australia. The modular design of the hybrid, subsurface-flow reedbed system offered 5 control points where monitoring and management of the treatment train could be carried out. Ten chemical parameters (chemical and biochemical oxygen demand, total organic carbon, total Kjeldahl nitrogen, ammonia nitrogen, nitrite nitrogen, nitrate nitrogen, total nitrogen, dissolved oxygen percentage saturation and suspended solids) and 4 microbial parameters (total coliform, Escherichia coli, enterococci and Clostridium perfringens) reached satisfactory levels as a result of the treatment process. Health requirements for safe horticultural irrigation were met by the outlet of the second reedbed, providing a high level of treatment-backup capacity in terms of the remaining 2 reedbeds. This suggested that chlorination was a redundant backup precaution in treating irrigation water to the acceptable regional guideline level for all horticultural uses, including the spray irrigation of salad crops eaten raw. PMID- 26282759 TI - Influence of liquid-volume and airflow rates on spray application quality and homogeneity in super-intensive olive tree canopies. AB - Olive is a key crop in Europe, especially in countries around the Mediterranean Basin. Optimising the parameters of a spray is essential for sustainable pesticide use, especially in high-input systems, such as the super-intensive hedgerow system. Parameters may be optimised by adjusting the applied volume and airflow rate of sprays, in addition to the liquid to air proportion and the relationship between air velocity and airflow rate. Two spray experiments using a commercial airblast sprayer were conducted in a super-intensive orchard to study how varying the liquid volume rate (testing volumes of 182, 619, and 1603 l ha( 1)) and volumetric airflow rate (with flow rates of 11.93, 8.90, and 6.15 m(3) s( 1)) influences the coverage parameters and the amount and distribution of deposits in different zones of the canopy.. Our results showed that an increase in the application volume raised the mean deposit and percentage coverage, but decreased the application efficiency, spray penetration, and deposit homogeneity. Furthermore, we found that the volumetric airflow rate had a lower influence on the studied parameters than the liquid volume; however, an increase in the airflow rate improved the application efficiency and homogeneity to a certain threshold, after which the spray quality decreased. This decrease was observed in the high-flow treatment. Our results demonstrate that intermediate liquid volume rates and volumetric airflow rates are required for the optimal spraying of pesticides on super-intensive olive crops, and would reduce current pollution levels. PMID- 26282760 TI - Polymorphism of the glucosyltransferase gene (ycjM) in Escherichia coli and its use for tracking human fecal pollution in water. AB - This study examined polymorphism of the glucosyltransferase gene (ycjM) in fecal Escherichia coli isolates and evaluated the use of the sequence polymorphism for measuring human fecal pollution in water. Significant nucleotide variations were observed through comparative analysis of the ycjM sequences of 70 E. coli strains isolated from the feces of humans, domestic livestock, and wild animals. Three distinct types of ycjM sequences were found: universal-ycjM, human/chicken-ycjM, and human-ycjM. Using the human-ycjM sequences, both a polymerase chain reaction (PCR), Hycj-PCR and a quantitative PCR, Hycj-qPCR, were developed. As shown by the Hycj-PCR amplification, the human-ycjM marker appeared to be highly associated with the E. coli strains isolated from human feces, based on the analysis of 370 E. coli strains isolated from humans and seven other animal species. Similarly, the human-ycjM marker was highly linked with human feces, as demonstrated by the Hycj-PCR assay, when using 337 fecal DNA samples from 16 host animal sources, including both domestic and wild animals. Overall, the specificity and sensitivity of the human-ycjM marker for differentiating between the feces of humans and those of nonhuman groups were 99.7% and 100%, respectively; the prevalence of the marker appeared to be greater than 50% in the human-feces-associated E. coli population. In addition, our study showed that the quantification of human E. coli by the Hycj-qPCR was linearly correlated with the anthropogenic activity within a watershed. Our study suggests that this novel human-ycjM marker and the resulting PCR-based methods developed should be useful for measuring human-associated E. coli and human fecal pollution in water. PMID- 26282761 TI - Fighting carbon loss of degraded peatlands by jump-starting ecosystem functioning with ecological restoration. AB - Degradation of ecosystems is a great concern on the maintenance of biodiversity and ecosystem services. Ecological restoration fights degradation aiming at the recovery of ecosystem functions such as carbon (C) sequestration and ecosystem structures like plant communities responsible for the C sequestration function. We selected 38 pristine, drained and restored boreal peatland sites in Finland and asked i) what is the long-term effect of drainage on the peatland surface layer C storage, ii) can restoration recover ecosystem functioning (surface layer growth) and structure (plant community composition) and iii) is the recovery of the original structure needed for the recovery of ecosystem functions? We found that drainage had resulted in a substantial net loss of C from surface layer of drained sites. Restoration was successful in regaining natural growth rate in the peatland surface layer already within 5 years after restoration. However, the regenerated surface layer sequestered C at a mean rate of 116.3 g m(-2) yr(-1) (SE 12.7), when a comparable short-term rate was 178.2 g m(-2) yr(-1) (SE 13.3) at the pristine sites. The plant community compositions of the restored sites were considerably dissimilar to those of pristine sites still 10 years after restoration. We conclude that ecological restoration can be used to jump-start some key peatland ecosystem functions even without the recovery of original ecosystem structure (plant community composition). However, the re-establishment of other functions like C sequestration may require more profound recovery of conditions and ecosystem structure. We discuss the potential economic value of restored peatland ecosystems from the perspective of their C sequestration function. PMID- 26282762 TI - Reactive transport modeling of subsurface arsenic removal systems in rural Bangladesh. AB - Subsurface Arsenic Removal (SAR) is a technique for in-situ removal of arsenic from groundwater. Extracted groundwater is aerated and re-injected into an anoxic aquifer, where the oxygen in the injected water reacts with ferrous iron in the aquifer to form hydrous ferric oxide (HFO). Subsequent extraction of groundwater contains temporarily lower As concentrations, because As sorbs onto the HFO. Injection, storage, and extraction together is called a cycle. A reactive transport model (RTM) was developed in PHREEQC to determine the hydrogeochemical processes responsible for As (im)mobilization during experimental SAR operation performed in Bangladesh. Oxidation of Fe(II) and As(III) were modeled using kinetic-rate expressions. Cation exchange, precipitation of HFO, and surface complexation, were modeled as equilibrium processes. A best set of surface complexation reactions and corresponding equilibrium constants was adopted from previous studies to simulate all 20 cycles of a SAR experiment. The model gives a reasonable match with observed concentrations of different elements in the extracted water (e.g., the r(2) value of As was 0.59 or higher). As concentrations in the extracted water are governed by four major processes. First, As concentration decreases in response to the elevated pH of injection water and likewise increases when native neutral pH groundwater flows in. Second, the sorption capacity for As increases due to the gradual buildup of HFO. Third, As sorption is enhanced by preferential removal of As(V). Fourth, competitive sorption of Si limits the capacity of freshly precipitated HFO for As sorption. Transferability of the developed reactive transport model was demonstrated through successful application of the model, without further calibration, to two additional SAR sites in Bangladesh. This gives confidence that the model could be useful to assess potential SAR performance at locations in Bangladesh based on local hydrogeochemical conditions. PMID- 26282763 TI - Intermittent rainstorms cause pulses of nitrogen, phosphorus, and copper in leachate from compost in bioretention systems. AB - Bioretention systems rely on vegetation and mixtures of soil, sand, and compost to filter stormwater runoff. However, bioretention systems can also leach metals and nutrients, and compost may be a major contributor to this leaching. To safely implement bioretention systems, it is crucial to determine the composition of compost leachate. We characterized and quantified the leachate composition of compost following intermittent, simulated storm events. Columns of municipal compost were irrigated to simulate 6-month, 24-hour rain storms in the Seattle Tacoma region. Outflow was analyzed for pH, electrical conductivity (EC), particulate concentration, surface tension, dissolved organic carbon (DOC), nitrogen, phosphorus, and copper. Results indicate a decrease of chemical concentrations over the course of individual storms and following repeated storms, but each new storm released another peak of constituents. The decrease in phosphorus, copper, and DOC concentrations with repeated storms was slower than for nitrate and EC. Nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR) showed that the DOC consisted mainly of aliphatic and aromatic components typical of fulvic and humic acids. Less than 3% of the original copper content from the compost leached out even after nine storm events. Nonetheless, copper concentrations in the leachate exceeded regulatory discharge standards. Our results show that compost can serve as a sustained source of leaching of nutrients and metals. PMID- 26282764 TI - Occurrence of benzophenone-3 in indoor air from Albany, New York, USA, and its implications for inhalation exposure. AB - Benzophenone-3 (BP-3) is a widespread environmental contaminant and an estrogenic compound. Very little is known with regard to the occurrence in indoor air and the inhalation exposure of humans to BP-3. In this study, 81 indoor air samples were collected from various locations in Albany, New York, USA, in 2014 and analyzed for BP-3 by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). BP-3 was found in all indoor air samples and the overall concentrations in bulk air (vapor plus particulate phases) were in the range of 0.19-72.0 ng/m(3) (geometric mean: 2.67 ng/m(3)). The highest concentrations (geometric mean: 10.7 ng/m(3)) were found in cars, followed by barber shops (6.57) ? public places (5.75)>homes (3.27) ? offices (1.96) ? garages (1.04) ? laboratories (0.47). The estimated geometric mean daily intake (EDI) of BP-3 for infants, toddlers, children, teenagers, and adults through indoor air inhalation from homes was 1.83, 1.74, 1.18, 0.69, and 0.51 ng/kg bw/day, respectively. Although high concentrations of BP-3 were measured in some microenvironments, the estimated contribution of indoor air to total BP-3 intake was <5% of the total BP-3 intake in humans. This is the first survey on the occurrence of BP-3 in indoor air. PMID- 26282765 TI - A hydrological-economic model for sustainable groundwater use in sparse-data drylands: Application to the Amtoudi Oasis in southern Morocco, northern Sahara. AB - A hydrological-economic model is introduced to describe the dynamics of groundwater-dependent economics (agriculture and tourism) for sustainable use in sparse-data drylands. The Amtoudi Oasis, a remote area in southern Morocco, in the northern Sahara attractive for tourism and with evidence of groundwater degradation, was chosen to show the model operation. Governing system variables were identified and put into action through System Dynamics (SD) modeling causal diagrams to program basic formulations into a model having two modules coupled by the nexus 'pumping': (1) the hydrological module represents the net groundwater balance (G) dynamics; and (2) the economic module reproduces the variation in the consumers of water, both the population and tourists. The model was operated under similar influx of tourists and different scenarios of water availability, such as the wet 2009-2010 and the average 2010-2011 hydrological years. The rise in international tourism is identified as the main driving force reducing emigration and introducing new social habits in the population, in particular concerning water consumption. Urban water allotment (PU) was doubled for less than a 100-inhabitant net increase in recent decades. The water allocation for agriculture (PI), the largest consumer of water, had remained constant for decades. Despite that the 2-year monitoring period is not long enough to draw long-term conclusions, groundwater imbalance was reflected by net aquifer recharge (R) less than PI+PU (G<0) in the average year 2010-2011, with net lateral inflow from adjacent Cambrian formations being the largest recharge component. R is expected to be much less than PI+PU in recurrent dry spells. Some low-technology actions are tentatively proposed to mitigate groundwater degradation, such as: wastewater capture, treatment, and reuse for irrigation; storm-water harvesting for irrigation; and active maintenance of the irrigation system to improve its efficiency. PMID- 26282766 TI - Mechanism of waste biomass pyrolysis: Effect of physical and chemical pre treatments. AB - To impart usability in waste based biomass through thermo-chemical reactions, several physical and chemical pre-treatments were conducted to gain an insight on their mode of action, effect on the chemistry and the change in thermal degradation profiles. Two different waste biomasses (Douglas fir, a softwood and hybrid poplar, a hardwood) were subjected to four different pre-treatments, namely, hot water pre-treatment, torrefaction, acid (sulphuric acid) and salt (ammonium phosphate) doping. Post pre-treatments, the changes in the biomass structure, chemistry, and thermal makeup were studied through electron microscopy, atomic absorption/ultra violet spectroscopy, ion exchange chromatography, and thermogravimetry. The pre-treatments significantly reduced the amounts of inorganic ash, extractives, metals, and hemicellulose from both the biomass samples. Furthermore, hot water and torrefaction pre-treatment caused mechanical disruption in biomass fibres leading to smaller particle sizes. Torrefaction of Douglas fir wood yielded more solid product than hybrid poplar. Finally, the salt pre-treatment increased the activation energies of the biomass samples (especially Douglas fir) to a great extent. Thus, salt pre-treatment was found to bestow thermal stability in the biomass. PMID- 26282767 TI - Single, competitive, and dynamic adsorption on activated carbon of compounds used as plasticizers and herbicides. AB - The main aim of this study was to investigate the single, competitive, and dynamic adsorption of phthalic acid (PA), bisphenol A (BPA), diphenolic acid (DPA), 2,4-dichlorophenoxy-acetic acid (2,4-D), and 4-chloro-2 methylphenoxyacetic acid (MCPA) on two activated carbons with different chemical natures and similar textural characteristics. The adsorption mechanism was also elucidated by analyzing the influence of solution pH and ionic strength. The activated carbons demonstrated high adsorption capacity to remove all micropollutants due to the presence of active sites on their surfaces, which increase dispersive interactions between the activated carbon graphene layers and the aromatic ring of pollutants. The adsorption capacity of the activated carbons increased in the order: DPA=2 attempts, and 3 failed to develop a clinical reaction. Four of 14 initiated treatment without a clinical reaction or a previous sensitization. Eleven of 14 patients experienced regrowth, 7 with previous sensitization and 4 without. LIMITATIONS: This observational study is limited by sample size. CONCLUSIONS: SADBE sensitization regimens and reactions vary widely, and the absence of an initial eczematous reaction to sensitization does not predict a failed response with continued SADBE treatment. PMID- 26282798 TI - Point: What's in a name? PMID- 26282799 TI - Counterpoint: The "dysplastic" nevus: What I do and do not believe. PMID- 26282800 TI - What costs nothing is worth nothing!: Is it okay to treat a benign lesion for free as part of an examination that involves treatment of several nonbenign lesions? PMID- 26282801 TI - Seasonal variation of acne and psoriasis: A 3-year study using the Physician Global Assessment severity scale. PMID- 26282802 TI - Psoriasis and herpes simplex virus are highly stigmatizing compared with other common dermatologic conditions: A survey-based study. PMID- 26282803 TI - Reflections on smart phones, tablets, and ultraviolet (UV) light: Should we worry?: An observational study. PMID- 26282804 TI - FLG (filaggrin) null mutations and sunlight exposure: Evidence of a correlation. PMID- 26282805 TI - Dermoscopy of cutaneous neurofibromas associated with neurofibromatosis type 1. PMID- 26282806 TI - Different dermoscopic patterns of palmoplantar and nonpalmoplantar lichen nitidus. PMID- 26282807 TI - Nicotine staining of the hair and nails. PMID- 26282808 TI - Peristomal pyoderma gangrenosum (PG): A simple hydrocolloid dressing technique to promote wound healing. PMID- 26282809 TI - A simple method for maintaining control of sutures to prevent sharps injuries and protect aseptic conditions. PMID- 26282810 TI - Recreation of the alar crease using the inverted horizontal mattress suture technique. PMID- 26282811 TI - Could a simple microbiological culture and an antibiogram guide the treatment of our patients with papulopustular rosacea (PPR)? PMID- 26282812 TI - Reply to: "Could a simple microbiological culture and an antibiogram guide the treatment of our patients with papulopustular rosacea?". PMID- 26282813 TI - Should dermatopathologists disclose serious diagnostic errors to patients? PMID- 26282814 TI - Reply: Medical error disclosure and patient compensation. PMID- 26282815 TI - Comment on "Time to update guidelines on screening for latent tuberculosis infection in dermatologic patients being treated with tumor necrosis factor-alfa inhibitors". PMID- 26282816 TI - Annual screening for tuberculosis in patients on TNF-alfa antagonists. PMID- 26282817 TI - Reply to: "Comment on 'Time to update guidelines on screening for latent tuberculosis infection in dermatologic patients being treated with tumor necrosis factor-alfa inhibitors'". PMID- 26282822 TI - Dermoscopy aids the diagnosis of crusted scabies in an erythrodermic patient. PMID- 26282823 TI - Darier disease: Dermoscopy, confocal microscopy, and histologic correlations. PMID- 26282824 TI - An imidazolyl-pyreno-imidazole conjugate as a cyanide sensor and a set-reset memorized sequential logic device. AB - In this work a pyrenyl-bisimidazole receptor has been synthesized and fully characterized by standard analytical tools and spectroscopic techniques including single crystal X-ray crystallography. Crystal structure analysis shows the occurrence of strong pi-pi and CH-pi interactions among the adjacent Py-BiimzH2 units. Moreover, each NH proton on the imidazole ring is involved in strong intermolecular hydrogen bonding interactions with N atoms of the neighboring unit forming infinite chains. The absorption and both steady state and time-resolved emission properties of the compound were found to be modulated to a significant extent by selective inorganic anions and transition metal cations in solution. Theoretical calculations employing density functional theory (DFT) and time dependent density functional theory (TD-DFT) were carried out and good correlation between the experimental and the TD-DFT calculated results led to the accurate assignment of the main absorption and emission bands of the original compound as well as its anionic and metal complexes. More importantly, the compound can act as an efficient ratiometric optical chemosensor for CN(-) in H2O DMSO (9 : 1) media. The anion sensing properties of the receptor was thoroughly investigated in both neat DMSO as well as mixed H2O-DMSO (9 : 1) media through different channels. From the response profiles in terms of absorption or emission intensity and wavelength towards inorganic ions (Cu(2+) and CN(-)), we developed a molecular system which can mimic sequential Boolean logic functions of XOR, OR, XNOR and NOR logic gates. Moreover, we were able to construct a memory device which nicely demonstrates the "Write-Read-Erase-Read" behavior. PMID- 26282825 TI - Novel roles and therapeutic targets of Epstein-Barr virus-encoded latent membrane protein 1-induced oncogenesis in nasopharyngeal carcinoma. AB - Epstein-Barr virus (EBV) was first discovered 50 years ago as an oncogenic gamma 1 herpesvirus and infects more than 90% of the worldwide adult population. Nasopharyngeal carcinoma (NPC) poses a serious health problem in southern China and is one of the most common cancers among the Chinese. There is now strong evidence supporting a role for EBV in the pathogenesis of NPC. Latent membrane protein 1 (LMP1), a primary oncoprotein encoded by EBV, alters several functional and oncogenic properties, including transformation, cell death and survival in epithelial cells in NPC. LMP1 may increase protein modification, such as phosphorylation, and initiate aberrant signalling via derailed activation of host adaptor molecules and transcription factors. Here, we summarise the novel features of different domains of LMP1 and several new LMP1-mediated signalling pathways in NPC. When then focus on the potential roles of LMP1 in cancer stem cells, metabolism reprogramming, epigenetic modifications and therapy strategies in NPC. PMID- 26282826 TI - Sleeping on the floor decreases insecticide treated bed net use and increases risk of malaria in children under 5 years of age in Mbita District, Kenya. AB - Children who sleep on the floor are less likely to use long-lasting insecticidal nets (LLINs); however, the relationship between sleeping location and Plasmodium falciparum infection has not been investigated sufficiently. This study revealed whether sleeping location (bed vs floor) is associated with P. falciparum infection among children 7-59 months old. More than 60% of children slept on the floor. Younger children were significantly more likely to sleep in beds [odds ratio, OR 2.31 (95% confidence interval (CI) 2.02-2.67)]. Nearly 70% of children slept under LLINs the previous night. LLIN use among children who slept on the floor was significantly less than ones sleeping in beds [OR 0.49 (95% CI 0.35 0.68)]. The polymerase chain reaction (PCR) based P. falciparum infection rate and slide based infection rate were 65.2 and 29.7%, respectively. Both infections were significantly higher among children slept on the floor [OR1.51 (95% CI 1.08 2.10) for PCR base, OR 1.62 (95% CI 1.14-2.30) for slide base] while net availability was not significant. Sleeping location was also significant for slide based infection with fever (? 37.5 degrees C) [2.03 (95% CI 1.14-3.84)] and high parasitemia cases (parasite ? 2500 uL(-1)) [2.07 (95% CI 1.03-4.50)]. The results suggest that sleeping location has a direct bearing on the effectiveness of LLINs. PMID- 26282827 TI - Algorithms that eliminate the effects of calibration artefact and trial-imposed offsets of Masimo oximeter in BOOST-NZ trial. AB - The displayed readings of Masimo pulse oximeters used in the Benefits Of Oxygen Saturation Targeting (BOOST) II and related trials in very preterm babies were influenced by trial-imposed offsets and an artefact in the calibration software. A study was undertaken to implement new algorithms that eliminate the effects of offsets and artefact. In the BOOST-New Zealand trial, oxygen saturations were averaged and stored every 10 s up to 36 weeks' post-menstrual age. Two-hundred and fifty-seven of 340 babies enrolled in the trial had at least two weeks of stored data. Oxygen saturation distribution patterns corresponding with a +3 % or -3 % offset in the 85-95 % range were identified together with that due to the calibration artefact. Algorithms involving linear and quadratic interpolations were developed, implemented on each baby of the dataset and validated using the data of a UK preterm baby, as recorded from Masimo oximeters with the original software and a non-offset Siemens oximeter. Saturation distributions obtained were compared for both groups. There were a flat region at saturations 85-87 % and a peak at 96 % from the lower saturation target oximeters, and at 93-95 and 84 % respectively from the higher saturation target oximeters. The algorithms lowered the peaks and redistributed the accumulated frequencies to the flat regions and artefact at 87-90 %. The resulting distributions were very close to those obtained from the Siemens oximeter. The artefact and offsets of the Masimo oximeter's software had been addressed to determine the true saturation readings through the use of novel algorithms. The implementation would enable New Zealand data be included in the meta-analysis of BOOST II trials, and be used in neonatal oxygen studies. PMID- 26282828 TI - A twist of nature--the significance of atropisomers in biological systems. AB - Recently identified natural atropisomeric compounds with potential medicinal applications are presented. The ability of natural receptors to possess differential binding between atropisomers is an important factor when considering active and inactive atropisomeric drugs, and has required the development of new techniques for atropselective synthesis of desired targets. Advances in this field therefore have significant relevance to modern pharmaceutical and medicinal chemistry. The atropisomeric natural products discussed include hibarimicinone, flavomannins, talaromannins, viriditoxin, rugulotrosin A, abyssomicin C, marinopyrroles, dixiamycins, streptorubin B, ustiloxins A-F, haouamine A, bisnicalaterines, and tedarene B, all of which show significant potential as leads in antibiotic, antiviral and anticancer studies. The importance for the development of common practices regarding atropisomer recognition and classification is also emphasized. PMID- 26282830 TI - Face adaptation in an isolated population of African hunter-gatherers: Exposure influences perception of other-ethnicity faces more than own-ethnicity faces. AB - Previous experiments have demonstrated that exposure to faces can change the perception of normality in new faces, such that faces similar to those at exposure appear more normal. Here we examined how experience influences adaptation effects in African Hadza hunter-gatherers, who have limited experience with White faces. We exposed participants to sets of either Hadza or White European faces that were manipulated to possess either wide-spaced or narrow spaced eyes. We collected normality judgments both pre-exposure and post-exposure by showing pairs of images, one with wide-spaced and one with narrow-spaced eyes. Examining the difference between the pre-exposure and post-exposure judgments revealed that participants selected an increased number of images that were congruent with the faces to which they had been exposed. The change in normality judgments was strongest for White faces, suggesting that representations of White ethnicity faces are more malleable and less robust to adaptation, potentially because of the decreased experience that individuals had with them. A second experiment using the same test stimuli with a sample of White participants revealed equivalent adaptation effects for both Hadza and White faces. These data highlight the role of experience on the high-level visual adaptation of faces. PMID- 26282831 TI - Cell-phone use diminishes self-awareness of impaired driving. AB - Multitasking diminishes the self-awareness of performance that is often essential for self-regulation and self-knowledge. Participants drove in a simulator while either talking or not talking on a hands-free cell phone. Following previous research, participants who talked on a cell phone made more serious driving errors than control participants who did not use a phone while driving. Control participants' assessments of the safeness of their driving and general ability to drive safely while distracted were negatively correlated with the actual number of errors made when they were driving. By contrast, cell-phone participants' assessments of the safeness of their driving and confidence in their driving abilities were uncorrelated with their actual errors. Thus, talking on a cell phone not only diminished the safeness of participants' driving, it diminished their awareness of the safeness of their driving. PMID- 26282829 TI - Perception and action influences on discrete and reciprocal bimanual coordination. AB - For nearly four decades bimanual coordination, "a prototype of complex motor skills" and apparent "window into the design of the brain," has been intensively studied. Past research has focused on describing and modeling the constraints that allow the production of some coordination patterns while limiting effective performance of other bimanual coordination patterns. More recently researchers have identified a coalition of perception-action constraints that hinder the effective production of bimanual skills. The result has been that given specially designed contexts where one or more of these constraints are minimized, bimanual skills once thought difficult, if not impossible, to effectively produce without very extensive practice can be executed effectively with little or no practice. The challenge is to understand how these contextual constraints interact to allow or inhibit the production of complex bimanual coordination skills. In addition, the factors affecting the stability of bimanual coordination tasks needs to be re conceptualized in terms of perception-related constraints arising from the environmental context in which performance is conducted and action constraints resident in the neuromotor system. PMID- 26282833 TI - The use of carbon monoxide as a probe molecule in spectroscopic studies for determination of exposed gold sites on TiO2. AB - The sol immobilisation technique, in which a stabilising ligand (such as polyvinyl alcohol or polyvinyl pyridine) can be used to tune metal particle size and composition, has become a valuable method of making supported nanoparticle catalysts. An unfortunate consequence of the stabilising ligand is that often access of reactant molecules to the metal nanoparticle surface is impeded. Several methods have been proposed for the removal of these ligands, though determination of the degree of their success is difficult. Here, we demonstrate the use of in situ infrared and UV-Vis spectroscopy to elucidate the access of carbon monoxide to the surface of Au/TiO2 catalysts before and after various ligand removal treatments. These were contrasted with a catalyst prepared by deposition precipitation prepared in the absence of stabilising ligand as a control. Changes were observed in the infrared spectrum, with the wavenumber of carbon monoxide linearly bonded to Au for catalysts shifting before and after ligand removal, which correlated well with the activity of the catalyst for carbon monoxide oxidation. Also the extent of shifting of the Au surface resonance plasmon band on the addition of carbon monoxide, observed by UV-Vis, also correlated well with catalyst activity. These simple methods can be used to determine the quantity of exposed metal sites after a ligand removal treatment and so determine the treatments effectiveness. PMID- 26282832 TI - Dietary glycemia as a determinant of health and longevity. AB - The role of diet in extending lifespan and healthspan has been the subject of much research and debate. Our recent epidemiological and in vivo data suggest that carbohydrate quality can be a major determinant in prolonging eye health. Additionally, excessive carbohydrate intake can contribute to the exacerbation of many different diseases. The metabolic diversity of the tissues that are affected by excessive carbohydrate intake suggests that dietary carbohydrate quality may affect cellular homeostasis. PMID- 26282834 TI - New insights into cellular alpha-synuclein homeostasis in health and disease. AB - alpha-Synuclein (alphaSyn) is a highly abundant neuronal protein whose exact structure and function are under debate. Misfolding and aggregation of this normally soluble, 140-residue polypeptide underlies a group of neurodegenerative disorders called synucleinopathies, including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The alphaSyn field has focused increasing attention on the hypotheses that certain aggregates of alphaSyn may be directly toxic to the neurons in which they arise and/or that aggregates can be released from some neurons and diffuse by undefined mechanisms to other neurons to seed alphaSyn in the recipient cells, thus propagating neuropathology by a non-cell autonomous process ('pathogenic spread'). While intense interest in these hypotheses has led to new approaches and tools to model aspects of the disorders, it is important to analyze which molecular events initiate alphaSyn aggregation inside neurons in the first place. Here, we review new insights into how neuronal alphaSyn homeostasis may be maintained under physiological conditions but perturbed by pathological factors. PMID- 26282835 TI - Hybrids of acylated homoserine lactone and nitric oxide donors as inhibitors of quorum sensing and virulence factors in Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa is an opportunistic pathogen causing a variety of life threatening diseases such as cystic fibrosis and nosocomial infections in burn victims. The ability of P. aeruginosa to cause infection is attributed to the production of virulence factors such as pyocyanin and elastases. These virulence factors are under the control of quorum sensing (QS) a cell to cell communication process controlled by small diffusible signalling molecules based on N-acyl homoserine lactones (AHLs) known as autoinducers. The inhibition of QS and thereby virulence factors is seen as a potential new anti-infective strategy. Additionally, the role of nitric oxide (NO) in downstream processes in bacteria such as biofilm dispersal, motility, virulence and antimicrobial defence systems is gaining attention and could be used to control bacterial. Herein we report the design and synthesis of hybrid compounds based on AHL signalling molecules and NO donors as anti-infective agents. A series of AHL-NO hybrids were synthesised and potent inhibitors of QS and virulence factors of P. aeruginosa were identified. This research has led to conversion of agonist AHLs to antagonist AHLs with dual properties of QS inhibition and NO release. PMID- 26282837 TI - Estimating body composition from skinfold thicknesses and bioelectrical impedance analysis in cystic fibrosis patients. AB - BACKGROUND: The accuracy of body composition estimates based on skinfold thickness measurements and bioelectrical impedance analysis (BIA) is not yet adequately explored in cystic fibrosis (CF). Using DXA as reference method we verified the accuracy of these techniques and identified predictors of body composition specific for CF. METHODS: One hundred forty-two CF patients (age range: 8-31 years) underwent a DXA scan. Body fat percentage (BF%) was estimated from skinfolds, while fat free mass (FFM) from single-frequency 50 kHz BIA. RESULTS: Bland-Altman analysis showed poor intra-individual agreement between body composition data provided by DXA and BF% estimated from skinfolds or FFM estimated from BIA. The skinfolds of the upper arm were better predictors of BF% than BMI, while compared to other BIA measurements the best predictor of FFM was the R-index (Height(2)/Resistance). CONCLUSIONS: Due to poor accuracy at individual level, the estimates of body composition obtained from these techniques cannot be part of the standard nutritional assessment of CF patients until reliable CF-specific equations will become available. BMI has limited value in predicting body fatness in CF patients and should be used in combination with other predictors. Skinfolds of the upper arm and R-index are strongly related to BF% and FFM and should be tested in a large CF population to develop specific predictive equations. PMID- 26282836 TI - DNA vaccines encoding the envelope protein of West Nile virus lineages 1 or 2 administered intramuscularly, via electroporation and with recombinant virus protein induce partial protection in large falcons (Falco spp.). AB - As West Nile virus (WNV) can cause lethal diseases in raptors, a vaccination prophylaxis of free-living and captive populations is desirable. In the absence of vaccines approved for birds, equine vaccines have been used in falcons, but full protection against WNV infection was not achieved. Therefore, two DNA vaccines encoding the ectodomain of the envelope protein of WNV lineages 1 and 2, respectively, were evaluated in 28 large falcons. Four different vaccination protocols were used, including electroporation and booster-injections of recombinant WNV domain III protein, before challenge with the live WNV lineage 1 strain NY99. Drug safety, plasmid shedding and antibody production were monitored during the vaccination period. Serological, virological, histological, immunohistochemical and molecular biological investigations were performed during the challenge trials. Antibody response following vaccination was low overall and lasted for a maximum of three weeks. Plasmid shedding was not detected at any time. Viremia, mortality and levels, but not duration, of oral virus shedding were reduced in all of the groups during the challenge trial compared to the non vaccinated control group. Likewise, clinical scoring, levels of cloacal virus shedding and viral load in organs were significantly reduced in three vaccination groups. Histopathological findings associated with WNV infections (meningo encephalitis, myocarditis, and arteritis) were present in all groups, but immunohistochemical detection of the viral antigen was reduced. In conclusion, the vaccines can be used safely in falcons to reduce mortality and clinical signs and to lower the risk of virus transmission due to decreased levels of virus shedding and viremia, but full protection was not achieved in all groups. PMID- 26282838 TI - Tigecycline-induced acute pancreatitis in a cystic fibrosis patient: A case report and literature review. AB - PURPOSE: The purpose of this case report is to increase awareness of tigecycline associated pancreatitis, specifically in patients who may be predisposed to develop pancreatitis. CASE SUMMARY: A 22-year-old male with cystic fibrosis developed acute bronchitis, with sputum cultures significant for Mycobacterium chelonae. He was started on tigecycline on two separate occasions, in each case developing pancreatitis as evidenced by symptomatology, elevated pancreatic enzymes and, in one case, by CT imaging. On both occasions, symptomatology improved and enzymes normalized after discontinuation of tigecycline. DISCUSSION: Current literature including two recent review pieces is discussed. The unique aspects of the case are highlighted, including the particular risk of drug associated pancreatitis in those with cystic fibrosis. CONCLUSION: The results of this case, in the context of current literature, suggest that clinicians should be aware of the potential for pancreatitis when using tigecycline. Clinicians should be particularly mindful of this complication in patients with comorbidities that might increase the risk of pancreatitis above that of the general population. PMID- 26282839 TI - The pharmacokinetics and toxicity of morning vs. evening tobramycin dosing for pulmonary exacerbations of cystic fibrosis: A randomised comparison. AB - BACKGROUND: Circadian variation in renal toxicity of aminoglycosides has been demonstrated in animal and human studies. People with CF are frequently prescribed aminoglycosides. Altered pharmacokinetics of aminoglycosides are predictive of toxicity. AIM: To investigate whether the time of day of aminoglycoside administration modulates renal excretion of tobramycin and toxicity in children with CF. To determine whether circadian rhythms are disrupted in children with CF during hospital admission. METHODS: Children (age 5 18years) with CF scheduled for tobramycin therapy were randomly allocated to receive tobramycin at 0800 or 2000h. Serum tobramycin levels were drawn at 1h and between 3.5 and 5h post-infusion between days 5 and 9 of therapy. Melatonin levels were measured serially at intervals from 1800h in the evening until 1200h on the next day. Circadian rhythm was categorised as normal when dim light melatonin onset was demonstrated between 1800 and 2200h and/or peak melatonin levels were observed during the night. Weight and spirometry were measured at the start and end of the therapy. Urinary biomarkers of kidney toxicity (KIM1, NAG, NGAL, IL-18 and CysC) were assayed at the start and end of the course of tobramycin. RESULTS: Eighteen children were recruited to the study. There were no differences in renal clearance between the morning and evening groups. The increase in urinary KIM-1 was greater in the evening dosage group compared to the morning group (mean difference, 0.73ng/mg; 95% CI, 0.14 to 1.32; p=0.018). There were no differences in the other urinary biomarkers. There was normal circadian rhythm in 7/11 participants (64%). CONCLUSIONS: Renal elimination of tobramycin was not affected by the time of day of administration. Urinary KIM-1 raises the possibility of greater nephrotoxicity with evening administration. Four children showed disturbed circadian rhythm and high melatonin levels (ClinicalTrials.gov NCT01207245). PMID- 26282840 TI - Development of fluconazole resistance in a series of Candida parapsilosis isolates from a persistent candidemia patient with prolonged antifungal therapy. AB - BACKGROUND: Candida parapsilosis was the most common species causing candidemia in the 2010 China Hospital Invasive Fungal Surveillance Net (CHIF-NET) database. Compared to Candida albicans, the description of azole resistance and mechanisms in C. parapsilosis is very limited. We report a patient with C. parapsilosis candidemia over several months, due to a probable intravascular source, who developed fluconazole resistance after prolonged treatment. CASE PRESENTATION: An 82 year-old male had a hospital admission of approximately 1.5 years duration. He was initially admitted with acute pancreatitis. Prior to succumbing to the illness, he developed candidemia and treated with three antifungal drugs for nearly 5 months, at suboptimal doses and without source control. Following treatment, 6 blood cultures were still positive for C. parapsilosis. The last 2 strains were resistant to fluconazole (MICs 32 MUg/mL) and intermediate to voriconazole (MICs 0.5 MUg/mL). Microsatellite multilocus analysis indicated that the 6 isolates from the patient belonged to a single genotype. The first 4 isolates were susceptible to fluconazole (MICs 2 MUg/mL) and voriconazole (MICs 0.015-0.03 MUg/mL), which were slightly higher than susceptible control strains from other patients. Overexpression of MDR1 genes were detected in the two resistant isolates, and this was associated with a homozygous mutation in MRR1 genes (T2957C /T2957C), with the amino acid exchange L986P. CONCLUSIONS: This case corroborates that the resistant C. parapsilosis isolates can emerge in the setting of complicated infections and the extensive use of antifungal agents, emphasizing the need for standardizing and improving the antifungal treatment as well as source control in the treatment of infection diseases. PMID- 26282841 TI - Effects of Polydopamine Functionalization on Boron Nitride Nanotube Dispersion and Cytocompatibility. AB - Boron nitride nanotubes (BNNTs) have unique physical properties, of value in biomedical applications; however, their dispersion and functionalization represent a critical challenge in their successful employment as biomaterials. In the present study, we report a process for the efficient disentanglement of BNNTs via a dual surfactant/polydopamine (PD) process. High-resolution transmission electron microscopy (HR-TEM) indicated that individual BNNTs become coated with a uniform PD nanocoating, which significantly enhanced dispersion of BNNTs in aqueous solutions. Furthermore, the cytocompatibility of PD-coated BNNTs was assessed in vitro with cultured human osteoblasts (HOBs) at concentrations of 1, 10, and 30 MUg/mL and over three time-points (24, 48, and 72 h). In this study it was demonstrated that PD-functionalized BNNTs become individually localized within the cytoplasm by endosomal escape and that concentrations of up to 30 MUg/mL of PD-BNNTs were cytocompatible in HOBs cells following 72 h of exposure. PMID- 26282843 TI - End of life care still requires improvement at nearly half of hospitals, report finds. PMID- 26282842 TI - The efficacy of a photolyase-based device on the cancerization field: a clinical and thermographic study. AB - BACKGROUND: At skin level, a cancerization field (CF) indicates some chronically photoexposed areas in which, besides a primary tumor, histological or biomolecular modifications without clinical signs are present. Active telethermography (ATT) allows us to observe the imaging of a hyperthermic halo (HH) surrounding the tumor . The Authors hypothesize HH as a possible expression of CF. OBJECTIVES: The aim of this study were to verify whether HHs have the same histological or immunohistochemical characteristics as the CF and, secondly, to evaluate the efficacy of a device containing the enzyme photolyase in modifying thermographic parameters in these area. METHODS: The study included 30 patients affected by actinic keratosis, evaluated clinically and by ATT at time 0 and after 3, 6 and 9 months. RESULTS: The ATT showed the presence of HHs in all the patients and, after the treatment, a significant modification of both the extension of these areas and the thermal parameters. In 5 patients for whom, while operated, two other biopsies were performed, respectively on the HH and on a perilesional non-hyperthermic area, in the HH, we detected a p53 and Ki 67 over expression. CONCLUSIONS: Our results indicate that ATT could represent a useful paraclinic method in identifying CFs in subjects at risk. PMID- 26282844 TI - Current genome editing tools in gene therapy: new approaches to treat cancer. AB - Gene therapy suggests a promising approach to treat genetic diseases by applying genes as pharmaceuticals. Cancer is a complex disease, which strongly depends on a particular genetic make-up and hence can be treated with gene therapy. From about 2,000 clinical trials carried out so far, more than 60% were cancer targeted. Development of precise and effective gene therapy approaches is intimately connected with achievements in the molecular biology techniques. The field of gene therapy was recently revolutionized by the introduction of "programmable" nucleases, including ZFNs, TALENs, and CRISPR, which target specific genomic loci with high efficacy and precision. Furthermore, when combined with DNA transposons for the delivery purposes into cells, these programmable nucleases represent a promising alternative to the conventional viral-mediated gene delivery. In addition to "programmable" nucleases, a new class of TALE- and CRISPR-based "artificial transcription effectors" has been developed to mediate precise regulation of specific genes. In sum, these new molecular tools may be used in a wide plethora of gene therapy strategies. This review highlights the current status of novel genome editing tools and discusses their suitability and perspectives in respect to cancer gene therapy studies. PMID- 26282846 TI - Health Related Quality of Life and support needs for sub-arachnoid haemorrhage survivors in New South Wales Australia. AB - BACKGROUND: Subarachnoid haemorrhage (SAH) is commonly a devastating injury with long lasting physical and psychosocial consequences for survivors. Support after hospital discharge through chronic care services for this patient group is limited. This study aimed to measure Health Related Quality of Life (HRQoL) and needs of survivors after discharge from hospital. METHODS: A population of patients that were diagnosed with SAH were contacted, up to 2 years post discharge, to participate in a postal survey including the Short Stroke Specific Quality of Life Scale (SSQoL-12), a service utilisation questionnaire and attitudes towards participating in a support group. FINDINGS: There were 28 responders. HRQoL was lowest in the psychosocial domain and particularly in relation to fatigue and memory. Most notably many responders indicated they wanted to be interviewed but a support group was not favoured with few responders (n=11) indicating interest with most in favour of a face to face format (n=10). CONCLUSIONS: HRQoL was reduced particularly in the psychosocial domain. Although there was low utilisation of support services in the post-acute care phase, these patients may benefit from greater opportunities to participate in both physical and psychosocial rehabilitation programs. PMID- 26282845 TI - Health allowance for improving the nutritional status and development of 3-5-year old left-behind children in poor rural areas of China: study protocol for a cluster randomised trial. AB - BACKGROUND: Left-behind children (LBC) are recognised as a new social group in China. LBC are young children who are abandoned in rural villages whilst their parents travel to distant urban centres for employment (a new generation of migrant workers). Following the rapid growth in the number of migrant workers, the LBC population is also rapidly increasing. These children are usually left to be raised by elderly grandparents, a single parent, or sometimes distant relatives or neighbours who have limited resources, tend to have a poor education and sometimes are in frail health. Over 40 % of the 61 million LBC in China who are under 5 years old are undernourished, which affects their long-term health and abilities. An intervention that combines a conditional cash transfer (CCT) with nutrition education offers a potential solution. METHODS/DESIGN: A cluster randomised controlled trial design will be used to allocate 40 villages to the intervention arm (20 villages) or control arm (20 villages). The caregivers and all of the 3-5-year-old LBC will be the target population. Caregivers in the intervention arm will receive a cash allowance conditional on attending nutrition education sessions, ensuring that the LBC will use basic public health services over a 12-month period. At the baseline, midterm (month 6) and end (month 12) of the intervention period, evaluations will be conducted in all 40 villages. Multilevel generalised linear models will be used to analyse the impact of the intervention on nutrition status and other outcomes, adjusting for baseline levels using an analysis of covariance approach. The cost of the intervention will also be estimated. DISCUSSION: If found to be cost-effective, the findings will inform the development of a sustainable model to improve nutrition status among LBC in rural areas of China. TRIAL REGISTRATION: Chinese Trial Register (ChiCTR) identifier: CTXY-140003-2 . Registered on 19 Aug 2014. PMID- 26282847 TI - Improving the feline veterinary consultation: the usefulness of Feliway spray in reducing cats' stress. AB - OBJECTIVES: Going to the veterinary clinic is a stressful experience for most cats as they feel threatened when entering a new and confined environment. The aim of this research was to investigate if Feliway spray, when used on the table in the consultation room, can decrease cats' stress and ease their handling. METHODS: A randomised, double-blind, placebo-controlled clinical trial was developed, using a total sample of 87 cats of both sexes, castrated or intact, of any breed, aged >26 weeks. A Feliway spray and a placebo solution spray were tested in two different consultation rooms. During the first phase, Feliway spray was applied to the examination table of one room and the placebo spray in the other. After a washout period of 15 days the spray allocation was switched. After the first 15 mins of general questioning and physical examination carried out by the veterinarian, the observer assessed the stress levels of the cats based on a seven-level 'cat stress score', and the ease of handling based on a five-point 'scale of handling' developed by the authors. RESULTS: The study demonstrated that the use of Feliway spray leads to significant (P = 0.01) differences in cats' usual behaviour, according to their owners. With regard to stress, animals exposed to Feliway spray showed significantly lower stress levels than those treated with placebo (P = 0.02). Regarding the scale of handling, the scoring did not differ significantly between cats under the effect of Feliway spray and cats receiving placebo (P = 0.01). CONCLUSIONS AND RELEVANCE: This research shows that the use of Feliway spray on the examination table improves the welfare of cats by reducing their stress during veterinary consultations. Feliway spray significantly changed the behaviour of the cats in this study, and offers a simple and effective way to help decrease stress in cats during the consultation. PMID- 26282848 TI - Aiweixin, a traditional Uyghur medicinal formula, protects against chromium toxicity in Caenorhabditis elegans. AB - BACKGROUND: Aiweixin (AWX) is a traditional Uyghur medicine prescription, and has been mainly used to treat heart and brain diseases for a long time. Previous studies indicated that AWX had therapeutic effects in a rat model of myocardial ischemia reperfusion injury. In this study, we investigate whether AWX has protective effects against chromium toxicity in Caenorhabditis elegans (C. elegans). METHODS: The AWX decoction was the conventional product for clinical use. It was added into M9 buffer in a certain volume for the treatment to the wild-type C. elegans and mutational worms, daf-16, glp-1(notch), daf-2, rsks-1 and eat-2. Assays for hexavalent chromium {Cr(VI)} stress and reactive oxygen species (ROS) production were used. RESULTS: We found that AWX at moderate contents (0.083, 0.1, 0.125 volume of AWX/total volume) increased resistance of C. elegans to Cr(VI) exposure, although higher contents of AWX are toxic for C. elegans. The protective effect of AWX was DAF-16-dependent, but independent on the DAF-2, GLP-1, RSKS-1 and EAT-2. AWX (0.1 volume of AWX/total volume) significantly reduced ROS production of C. elegans induced by Cr(VI) exposure. CONCLUSION: These results indicated the AWX protected against the toxicity of Cr(VI) in C. elegans, and the oxidative stress protective mechanism in worms should be involved. PMID- 26282849 TI - High-Resolution Manometry Evaluation of the Pharynx and Upper Esophageal Sphincter Motility in Patients with Achalasia. AB - The motility of the pharynx and upper esophageal sphincter (UES) is still poorly understood. It is also unclear if the motility of this area may be compromised in patients with achalasia. This study aims to evaluate the motility of the pharynx, UES, and proximal esophagus in patients with esophageal achalasia. Sixty patients with achalasia underwent high-resolution manometry (HRM) (52 % females, mean age 54 years). Esophageal dilatation was classified according to the radiologic diameter in Type I (<4 cm): 6 %; Type II (4-7 cm): 36 %; Type III (7-10 cm): 34 %; and Type IV (>10 cm): 24 %. HRM classified 43 % of the patients as Chicago Type I and 57 % as Type II. Manometric parameters were compared to normal values obtained from a previous study in volunteers. The motility of the velopharynx showed short, premature, and hypertonic contraction. The epiglottis also showed hypertonic contraction. The UES had increased residual pressure. Chicago classification Type II patients had higher UES residual pressure (p = 0.03). The degree of esophageal dilatation did not correlate with manometric parameters. Achalasia may affect the motility of the pharyngo-upper esophageal area. The changes observed may represent functional alterations to prevent aspiration, especially in patients with Chicago classification Type II achalasia. PMID- 26282850 TI - Role and Operative Technique of Portal Venous Tumor Thrombectomy in Patients with Pancreatic Neuroendocrine Tumors. AB - INTRODUCTION: Venous tumor thrombi have been reported in as many as 33 % of patients with pancreatic neuroendocrine tumors (pNETs). Surgical thrombectomy is often used to manage tumor thrombi that develop in association with cancers of the liver or kidney. We have likewise used thrombectomy to extract portal venous tumor thrombi in selected cases of pNET. METHODS: We describe all cases of portal venous thrombectomy that were performed at our institution between 2007 and 2014 and illustrate the thrombectomy techniques we used in detail. In addition, we report the results of a PubMed search for English-language articles that were published between 1990 and 2014 and that described surgical therapy for portal venous thrombus developing in association with pNETs. RESULTS: Among 245 patients with pNET that underwent pancreatectomy at our institution, 26 (11 %) patients required surgical management of tumor involvement of the portal vein or its tributaries concomitant with pancreatectomy, including 9 (3.8 %) patients who underwent portal venous tumor thrombectomy. Eight cases describing surgical management of tumor thrombus including two additional cases of portal venous tumor thrombectomy were identified in the medical literature. Among patients with pNET who underwent thrombectomy at our institution, all nine had non-functioning tumors and eight (89 %) had tumors of the body and/or tail of the pancreas. Six (67 %) were treated with systemic therapy prior to pancreatectomy. Seven (78 %) patients are alive at a median follow-up of 33 months (range 3 to 97). CONCLUSION: Venous tumor thrombectomy may be used to safely and effectively extract thrombi from the portal venous system in selected patients with advanced pNET concomitant with pancreatectomy. PMID- 26282851 TI - SILS v SILS+1: a Case-Matched Comparison for Colorectal Surgery. AB - BACKGROUND: Single-incision laparoscopic surgery (SILS) is safe and feasible for benign and malignant colorectal diseases. SILS has comparable or improved outcomes compared to multiport laparoscopy but technical limitations when operating in the pelvis. To address these limitations, we developed an innovative SILS+1 approach using a single Pfannenstiel incision for pelvis access with one additional umbilical port. Our goal was to compare outcomes for SILS and SILS+1 in lower abdominal and pelvic colorectal surgery. METHODS: Review of a prospectively maintained database identified patients who underwent an elective reduced port laparoscopic lower abdominal/pelvic colorectal procedure from 2009 to 2014. Cases were stratified by approach: SILS versus SILS+1 then matched 1:2 on age, gender, body mass index (BMI), comorbidity, and procedure. Demographic, perioperative, and postoperative outcome variables were evaluated. The main outcome measures were operative time, conversion rate, length of stay, complication, morbidity, and mortality rates. RESULTS: One hundred thirty-two reduced port AR/LAR patients were evaluated-44 SILS and 88 SILS+1. The groups were similar in age, gender, BMI, and ASA class. The primary diagnosis in both cohorts was diverticulitis (90.9 % SILS, 87.5 % SILS+1), and main procedure performed an anterior rectosigmoidectomy (86.4 % SILS, 88.2 % SILS+1). Significantly more SILS+1 patients had previous abdominal surgery (p = 0.01). The operative time was significantly shorter in SILS+1 (mean 166.6 [SD 48.4] vs. 178.0 [SD 70.0], p = 0.03). The conversion rate to multiport or open surgery was also significantly lower with SILS+1 compared to SILS (1.1 vs. 11.4 %, p = 0.02). Postoperatively, the length of stay across the groups was similar. SILS trended towards higher complication and readmission rates (NS). There were no unplanned reoperations or mortality in either group. CONCLUSIONS: SILS+1 facilitates pelvic and lower abdominal colorectal surgery, with shorter operative times and lower conversion rates. The additional port improved visualization and outcomes without any impact on length of stay, readmission, or complication rates. PMID- 26282852 TI - Role of Slit2/Robo1 in trophoblast invasion and vascular remodeling during ectopic tubal pregnancy. AB - INTRODUCTION: For ectopic tubal pregnancy to be viable, it requires a supporting vascular network and functioning trophoblast. Slit2/Robo1 signaling plays an important role in placental angiogenesis during normal pregnancy. Hence, we here investigated whether or not Slit2/Robo1 signaling also had an impact in ectopic tubal pregnancy. METHODS: The Slit2 and Robo1 expression pattern relevant to trophoblast invasive behavior and vascular remodeling was studied in human tubal placenta obtained from patients with ectopic pregnancy (5-8weeks gestation), The trophoblast development, vascular architecture and Robo1 expression pattern were observed in Slit2 overexpression (Slit2-Tg) and C57BL mice placenta (E13.5 and E15.5). RESULTS: Marked with CK-7 and Vimentin, the vessel profiles of fallopian tube were classified into four stages. In the presence of extravillous trophoblast (EVT), stellate-shaped and polygonal-shaped EVTs were observed, and the stellate-shaped EVT showed the higher Slit2 expression (P < 0.01) but lower Robo1 expression (P < 0.05) than polygonal-shaped cells. By contrast, a temporary Slit2 up-regulation in remodeling vessel and Slit2 down-regulation in remodeled vessel of polygonal-shape extravillous trophoblast cells occurred in tubal pregnancies. In Slit2-Tg mice E13.5 and E15.5 placenta, Slit2 overexpression promoted vascular remodeling by increasing in the diameter of the maternal blood sinusoids and fetal capillaries, but enhanced the thickness of trophoblast and vasculature at E15.5 Slit2-Tg mice. CONCLUSIONS: The varying Slit2 and Robo1 expression in EVTs was associated with trophoblast invasion and probably plays an important role in the events of blood vessel remodeling of the fallopian tube tissues. PMID- 26282853 TI - The contribution of Toll-like receptors to placental inflammation in diet-induced maternal obesity. AB - Toll-like receptor (TLR)-regulated protein kinases and inflammatory cytokines were activated in fetal vascular smooth muscle cells (VSMC) treated with palmitate. Tumor necrosis factor (TNFalpha) and interleukin-6 (IL6) were increased and correlated with expression of TLRs in the labyrinth placentae of high fat (HF)-fed rats with increased plasma lipids and visceral adiposity. Thus, local induction of TLR signaling via saturated fatty acids (SFA) may in part contribute to placental inflammation in diet-induced maternal obesity. PMID- 26282854 TI - Transcriptional analysis of immune-related gene expression in p53-deficient mice with increased susceptibility to influenza A virus infection. AB - BACKGROUND: p53 is a tumor suppressor that contributes to the host immune response against viral infections in addition to its well-established protective role against cancer development. In response to influenza A virus (IAV) infection, p53 is activated and plays an essential role in inhibiting IAV replication. As a transcription factor, p53 regulates the expression of a range of downstream responsive genes either directly or indirectly in response to viral infection. We compared the expression profiles of immune-related genes between IAV-infected wild-type p53 (p53WT) and p53-deficient (p53KO) mice to gain an insight into the basis of p53-mediated antiviral response. METHODS: p53KO and p53WT mice were infected with influenza A/Puerto Rico/8/1934 (PR8) strain. Clinical symptoms and body weight changes were monitored daily. Lung specimens of IAV-infected mice were collected for analysis of virus titers and gene expression profiles. The difference in immune-related gene expression levels between IAV infected p53KO and p53WT mice was comparatively determined using microarray analysis and confirmed by quantitative real-time reverse transcription polymerase chain reaction. RESULTS: p53KO mice showed an increased susceptibility to IAV infection compared to p53WT mice. Microarray analysis of gene expression profiles in the lungs of IAV-infected mice indicated that the increased susceptibility was associated with significantly changed expression levels in a range of immune related genes in IAV-infected p53KO mice. A significantly attenuated expression of Ifng (encoding interferon (IFN)-gamma), Irf7 (encoding IFN regulator factor 7), and antiviral genes, such as Mx2 and Eif2ak2 (encoding PKR), were observed in IAV-infected p53KO mice, suggesting an impaired IFN-mediated immune response against IAV infection in the absence of p53. In addition, dysregulated expression levels of proinflammatory cytokines and chemokines, such as Ccl2 (encoding MCP 1), Cxcl9, Cxcl10 (encoding IP-10), and Tnf, were detected in IAV-infected p53KO mice during early IAV infection, reflecting an aberrant inflammatory response. CONCLUSION: Lack of p53 resulted in the impaired expression of genes involved in IFN signaling and the dysregulated expression of cytokine and chemokine genes in IAV-infected mice, suggesting an essential role of p53 in the regulation of antiviral and inflammatory responses during IAV infection. PMID- 26282856 TI - Violating body movement semantics: Neural signatures of self-generated and external-generated errors. AB - How do we recognize ourselves as the agents of our actions? Do we use the same error detection mechanisms to monitor self-generated vs. externally imposed actions? Using event-related brain potentials (ERPs), we identified two different error-monitoring loops involved in providing a coherent sense of the agency of our actions. In the first ERP experiment, the participants were embodied in a virtual body (avatar) while performing an error-prone fast reaction time task. Crucially, in certain trials, participants were deceived regarding their own actions, i.e., the avatar movement did not match the participant's movement. Self generated real errors and false (avatar) errors showed very different ERP signatures and with different processing latencies: while real errors showed a classical frontal-central error-related negativity (Ne/ERN), peaking 100ms after error commission, false errors elicited a larger and delayed parietal negative component (at about 350-400ms). The violation of the sense of agency elicited by false avatar errors showed a strong similarity to ERP signatures related to semantic or conceptual violations (N400 component). In a follow-up ERP control experiment, a subset of the same participants merely acted as observers of the avatar correct and error movements. This experimental situation did not elicit the N400 component associated with agency violation. Thus, the results show a clear neural dissociation between internal and external error-monitoring loops responsible for distinguishing our self-generated errors from those imposed externally, opening new avenues for the study of the mental processes underlying the integration of internal and sensory feedback information while being actors of our own actions. PMID- 26282857 TI - Does personalized medicine exist and can you test it in a clinical trial? AB - The idea that different patients will respond differently to the same treatment is not new. The recent advances in genomics and laboratory medicine have led to the hope that it will be possible to maximize the benefit and minimize the harms of each medical therapy by using an individuals' biomarker status to 'personalize' their treatment. The selection of treatment for each individual would then be determined, not just by their disease status (or an estimate of the risk of developing a disease or disease progression), but also by their genetic makeup or by other measurable characteristics, such as the level of a particular biomarker in the blood. This review discusses the extent to which personalized medicine might be applied in stroke, and the implications for global stroke health care. PMID- 26282855 TI - Multimodal connectivity of motor learning-related dorsal premotor cortex. AB - The dorsal premotor cortex (dPMC) is a key region for motor learning and sensorimotor integration, yet we have limited understanding of its functional interactions with other regions. Previous work has started to examine functional connectivity in several brain areas using resting state functional connectivity (RSFC) and meta-analytical connectivity modelling (MACM). More recently, structural covariance (SC) has been proposed as a technique that may also allow delineation of functional connectivity. Here, we applied these three approaches to provide a comprehensive characterization of functional connectivity with a seed in the left dPMC that a previous meta-analysis of functional neuroimaging studies has identified as playing a key role in motor learning. Using data from two sources (the Rockland sample, containing resting state data and anatomical scans from 132 participants, and the BrainMap database, which contains peak activation foci from over 10,000 experiments), we conducted independent whole brain functional connectivity mapping analyses of a dPMC seed. RSFC and MACM revealed similar connectivity maps spanning prefrontal, premotor, and parietal regions, while the SC map identified more widespread frontal regions. Analyses indicated a relatively consistent pattern of functional connectivity between RSFC and MACM that was distinct from that identified by SC. Notably, results indicate that the seed is functionally connected to areas involved in visuomotor control and executive functions, suggesting that the dPMC acts as an interface between motor control and cognition. PMID- 26282858 TI - Endogenous murine leukemia retroviral variation across wild European and inbred strains of house mouse. AB - BACKGROUND: Endogenous murine leukemia retroviruses (MLVs) are high copy number proviral elements difficult to comprehensively characterize using standard low throughput sequencing approaches. However, high throughput approaches generate data that is challenging to process, interpret and present. RESULTS: Next generation sequencing (NGS) data was generated for MLVs from two wild caught Mus musculus domesticus (from mainland France and Corsica) and for inbred laboratory mouse strains C3H, LP/J and SJL. Sequence reads were grouped using a novel sequence clustering approach as applied to retroviral sequences. A Markov cluster algorithm was employed, and the sequence reads were queried for matches to specific xenotropic (Xmv), polytropic (Pmv) and modified polytropic (Mpmv) viral reference sequences. CONCLUSIONS: Various MLV subtypes were more widespread than expected among the mice, which may be due to the higher coverage of NGS, or to the presence of similar sequence across many different proviral loci. The results did not correlate with variation in the major MLV receptor Xpr1, which can restrict exogenous MLVs, suggesting that endogenous MLV distribution may reflect gene flow more than past resistance to infection. PMID- 26282859 TI - The challenge of sustaining effectiveness over time: the case of the global network to stop tuberculosis. AB - Where once global health decisions were largely the domain of national governments and the World Health Organization, today networks of international organizations, governments, private philanthropies and other entities are actively shaping public policy. However, there is still limited understanding of how global networks form, how they create institutions, how they promote and sustain collective action, and how they adapt to changes in the policy environment. Understanding these processes is crucial to understanding their effectiveness: whether and how global networks influence policy and public health outcomes. This study seeks to address these gaps through the examination of the global network to stop tuberculosis (TB) and the factors influencing its effectiveness over time. Drawing from ~ 200 document sources and 16 interviews with key informants, we trace the development of the Global Partnership to Stop TB and its work over the past decade. We find that having a centralized core group and a strategic brand helped the network to coalesce around a primary intervention strategy, directly observed treatment short course. This strategy was created before the network was formalized, and helped bring in donors, ministries of health and other organizations committed to fighting TB-growing the network. Adaptations to this strategy, the creation of a consensus-based Global Plan, and the creation of a variety of participatory venues for discussion, helped to expand and sustain the network. Presently, however, tensions have become more apparent within the network as it struggles with changing internal political dynamics and the evolution of the disease. While centralization and stability helped to launch and grow the network, the institutionalization of governance and strategy may have constrained adaptation. Institutionalization and centralization may, therefore, facilitate short-term success for networks, but may end up complicating longer-term effectiveness. PMID- 26282860 TI - Participatory planning of a primary care service for people with severe mental disorders in rural Ethiopia. AB - Little is understood about the feasibility and acceptability of primary care based models of task-sharing care for people with severe mental disorders (SMDs) in low- and middle-income countries (LMICs). A participatory planning approach was adopted in preparation for the transition from hospital-delivered psychiatric care for SMD to a primary care-based, task-sharing model in a rural Ethiopian community. In this article, we present findings from community consultation meetings (n = 4), focus group discussions (n = 7) and in-depth interviews (n = 11) with key stakeholders (healthcare administrators and providers, caregivers, service-users and community leaders) which were carried out over a 2-year period in the context of ongoing dialogue with the community. The principle of local delivery of mental health services was agreed upon by all stakeholder groups. Key reasons for supporting local delivery were increased access for the majority due to proximity, reduced cost and reduced stress related to transportation. However, acceptance of the new service was qualified by concerns about the competence of staff to deliver a comprehensive and dependable service of equal quality to that currently provided at the hospital. Adequate training and support, as well as ensuring consistency of medication supply were identified as key components to ensure success. Encouragingly, our results suggest that there is significant support for the service change and an interest for the mobilization of community resources to support this. One of the study strengths was that we were able to present the different perspectives of multiple stakeholder groups. By nesting the study in an ongoing community-based cohort of people with SMD we were able to interview a more representative and empowered group of caregivers and service users than is often available in LMICs. Despite this, the extent to which service users are able to express their opinions is likely limited by their marginalized role in rural Ethiopian society. PMID- 26282862 TI - Defective Self-Renewal and Differentiation of GBA-Deficient Neural Stem Cells Can Be Restored By Macrophage Colony-Stimulating Factor. AB - Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the glucocerebrosidase gene (GBA), which encodes the lysosomal enzyme glucosylceramidase (GCase). Deficiency in GCase leads to characteristic visceral pathology and lethal neurological manifestations in some patients. Investigations into neurogenesis have suggested that neurodegenerative disorders, such as GD, could be overcome or at least ameliorated by the generation of new neurons. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are potential candidates for use in the treatment of neurodegenerative disorders because of their ability to promote neurogenesis. Our objective was to examine the mechanism of neurogenesis by BM-MSCs in GD. We found that neural stem cells (NSCs) derived from a neuronopathic GD model exhibited decreased ability for self-renewal and neuronal differentiation. Co-culture of GBA-deficient NSCs with BM-MSCs resulted in an enhanced capacity for self-renewal, and an increased ability for differentiation into neurons or oligodendrocytes. Enhanced proliferation and neuronal differentiation of GBA-deficient NSCs was associated with elevated release of macrophage colony-stimulating factor (M-CSF) from BM-MSCs. Our findings suggest that soluble M-CSF derived from BM-MSCs can modulate GBA deficient NSCs, resulting in their improved proliferation and neuronal differentiation. PMID- 26282863 TI - Association between sesamoiditis, subclinical ultrasonographic suspensory ligament branch change and subsequent clinical injury in yearling Thoroughbreds. AB - REASONS FOR PERFORMING STUDY: Sesamoiditis is a common radiological finding in yearling Thoroughbreds. The condition is believed to be associated with suspensory ligament branch injury (SLBI), which is known to affect racing performance. The presence of subclinical suspensory ligament branch change (SSLBC) in untrained yearlings has not been investigated. Associations between sesamoiditis, SSLBC and subsequent SLBI would allow more accurate prognoses to be made regarding the development of SLBI. They could also provide opportunity for intervention and prevention of SLBI. OBJECTIVES: To test our hypotheses that untrained yearling Thoroughbreds with sesamoiditis would be more likely to have ultrasonographic findings of SSLBC and those horses with concurrent sesamoiditis and SSLBC would be more likely to develop clinical suspensory ligament branch injury with training. STUDY DESIGN: Prospective, cohort, observational study. METHODS: Yearling Thoroughbreds located at a single training centre were evaluated at the onset of their training careers and for the next 9 months. Radiographic and ultrasonographic examination of bilateral forelimb proximal sesamoid bones and suspensory ligament branches was performed. RESULTS: Fifty horses were eligible, resulting in 200 forelimb sesamoid/suspensory ligament branch pairs. A significant relationship existed between possibly significant (PS) sesamoiditis and PS SSLBC (P<0.001). The odds ratio of sesamoids with PS sesamoiditis also demonstrating concurrent PS SSLBC was 5.1 (95% confidence interval 2.68-9.70, P<0.001). A significant relationship also existed between the concurrent presence of PS sesamoiditis and PS SSLBC and the subsequent development of clinical signs of SLBI (P<0.001, odds ratio 11.7, 95% confidence interval 4.1-33.4). CONCLUSIONS: The associations identified in this study highlight the importance of ultrasonographic examination of suspensory ligament branches in horses with PS sesamoiditis. This information should allow more accurate prognostic advice regarding potential SLBI development and also provide opportunities for intervention and prevention of clinical SLBI. THE SUMMARY IS AVAILABLE IN CHINESE - SEE SUPPORTING INFORMATION. PMID- 26282864 TI - Correlates of unmet needs and psychological distress in adolescent and young adults who have a parent diagnosed with cancer. AB - OBJECTIVE: Young people who have a parent with cancer experience elevated levels of psychological distress and unmet needs. In this study, we examined the associations between demographics, cancer variables and family functioning and levels of distress and unmet needs amongst young people who have a parent diagnosed with cancer. METHODS: Young people aged 12-24 years with a parent with cancer (n = 255) completed the Offspring Cancer Needs Instrument (unmet needs), the Kessler-10 (distress) and the Family Relationship Index (family functioning), along with measures of demographics and cancer variables (such as age, sex and time since cancer diagnosis). Variables associated with distress and unmet needs (including unmet need domains) were assessed using multiple linear regression. RESULTS: Being female and older, having more unmet cancer needs and poorer family functioning were associated with increased distress. Having a father with cancer, a shorter time since diagnosis and poor family functioning were associated with increased unmet needs. Family conflict and expressiveness were particularly important components of family functioning. Having a parent relapse with cancer was also associated with unmet needs in the domains of practical assistance, 'time out' and support from other young people who have been through something similar. CONCLUSIONS: Delineating factors associated with increased distress and unmet needs assist in identifying at-risk young people allowing improved assessment and tailoring of support to improve the psychosocial outcomes of young people impacted by parental cancer. PMID- 26282865 TI - Individual experiences following a 6-month exercise intervention: A qualitative study. AB - PURPOSE: Dropout is a common problem in various exercise interventions. The individual's experience is believed to greatly impact dropout, yet little is known about the individual experiences of taking part in exercise interventions. The aim of this study was to examine individuals' experiences following a self determination theory-based exercise intervention in order to gain understanding of how standardized interventions can be adjusted to fit individuals' specific needs, capacities, and circumstances. METHODS: A qualitative approach with semi structured interviews was conducted with eight informants (three male and five female) aged between 26 and 47 years, whom all had participated in a 6-month exercise intervention with individual coaching based on self-determination theory and motivational interviewing. The interviews were analyzed thematically with an inductive approach. RESULTS: Aspects that influenced the informants' motivation and participation in the exercise intervention were linked to three themes: the frames of the intervention, measurable changes, and the individual's context. The themes present information about the process and to what extent the informants felt that the intervention was adapted to fit their lives and needs. CONCLUSIONS: This study emphasizes the importance of individualizing exercise interventions to support individuals' diverse capacities and psychological needs. PMID- 26282866 TI - Orthorexia nervosa: An integrative literature review of a lifestyle syndrome. AB - Bratman first proposed orthorexia nervosa in the late 1990s, defining it an obsession with eating healthy food to achieve, for instance, improved health. Today, in the Swedish media, excessive exercising plays a central role in relation to orthorexia. A few review articles on orthorexia have been conducted; however, these have not focused on aspects of food and eating, sport, exercise, or a societal perspective. The overall aim of this study was to provide an overview and synthesis of what philosophies of science approaches form the current academic framework of orthorexia. Key questions were: What aspects of food and eating are related to orthorexia? What role do exercise and sports play in relation to orthorexia? In what ways are orthorexia contextualized? Consequently, the concept of healthism was used to discuss and contextualize orthorexia. The method used was an integrative literature review; the material covered 19 empirical and theoretical articles published in peer-reviewed journals. This review demonstrates a multifaceted nature of orthorexia research; this field has been examined from four different philosophies of science approaches (i.e., empirical-atomistic, empirical-atomistic with elements of empirical-holistic, empirical-holistic, and rational-holistic) on individual, social, and societal levels. The majority of the articles followed an empirical atomistic approach that focused on orthorexia as an individual issue, which was discussed using healthism. Our analysis indicates a need for (a) more empirical holistic research that applies interpretive qualitative methods and uses a social perspective of health, e.g., healthism and (b) examining the role of sports and exercise in relation to orthorexia that takes the problematizing of "orthorexic behaviours" within the sports context into account. PMID- 26282867 TI - "I tried so many diets, now I want to do it differently" - A single case study on coaching for weight loss. AB - In this single case study, the author presented an in-depth description and analysis of a coaching intervention with focus on weight loss, conducted over 10 sessions in the course of 17 months. The client was a well-educated woman in her late 30s, who had tried many different forms of dieting over the years-with little and no lasting effect. In his coaching approach, the author went beyond a pure behavioural change model, that is, based on the Health Belief Model, and tried to take a whole-life perspective, where the client learned to link specific events and habits in her work life and everyday life with specific eating habits. In their collaborative practice, coach and coachee initiated changes both in regard to diet, physical activity, and healthy life style, in general. In a theoretical section, the change in understanding with regard to overeating was presented. Finally, an intra-active model-viewing the client as a self-reflective individual-was used as theoretical basis. A narrative analysis of the first session and a cross-session examination was presented to show, analyse, and understand the procedure of the coaching approach. Finally, the voice of the coachee was heard in regard to her personal experiences during the process. The data material was based on audio recordings of selected sessions, notes written by the coach from every session, and final written reflections by the coachee. PMID- 26282868 TI - Understanding physical activity participation in spinal cord injured populations: Three narrative types for consideration. AB - The aim of this study was to identity the types of physical activity narratives drawn upon by active spinal injured people. More than 50 h of semi-structured life-story interview data, collected as part of larger interdisciplinary program of disability lifestyle research, was analysed for 30 physically active male and female spinal cord injury (SCI) participants. A structural narrative analysis of data identified three narrative types which people with SCI draw on: (1) exercise is restitution, (2) exercise is medicine, and (3) exercise is progressive redemption. These insights contribute new knowledge by adding a unique narrative perspective to existing cognitive understanding of physical activity behaviour in the spinal cord injured population. The implications of this narrative typology for developing effective positive behavioural change interventions are critically discussed. It is concluded that the identified narratives types may be constitutive, as well as reflective, of physical activity experiences and therefore may be a useful tool on which to base physical activity promotion initiatives. PMID- 26282869 TI - Future challenges for intervention research in health and lifestyle research - A systematic meta-literature review. AB - The overall aim of this systematic meta-literature review was to (1) summarize the findings of review studies focusing on health determinants, (2) give an overview of intervention studies that have been used to facilitate health and lifestyle, and (3) provide recommendations for future studies in health promotion. A literature review, using a meta-method, was conducted to identify health and lifestyle research based on research articles related to health changes. The search yielded a total of 561 unique citations and finally 24 citations remained. Of those, 11 studies focused on health determinants, whereas 13 focused on interventions for health promotion. Results from this meta synthesis led to four recommendations for the design of future intervention studies. (1) To increase the likelihood of capturing different biopsychosocial aspects of health, researchers from different scientific disciplines should collaborate in the design, implementation, and evaluation of the study. (2) It is recommended to use theoretical frameworks that focus on health determinants in longitudinal studies with a repeated measures design. (3) Studies should involve behavioral interventions. (4) Design face-to-face intervention studies where the participant can interact with other persons. PMID- 26282870 TI - Parent participation plays an important part in promoting physical activity. AB - Although physical activity (PA) is an important and modifiable determinant of health, in Sweden only 15% of boys and 10% of girls aged 15 years old achieve the recommended levels of PA 7 days per week. Adolescents' PA levels are associated with social influence exerted by parents, friends, and teachers. The purpose of this study was to describe parents' experiences of being a part of their adolescents' empowerment-inspired PA intervention. A qualitative interview study was performed at a school in the northern part of Sweden. A total of 10 parents were interviewed, and the collected data were analyzed with qualitative content analysis. Three subthemes were combined into one main theme, demonstrating that parents are one important part of a successful PA intervention. The life of an adolescent has many options and demands that make it difficult to prioritize PA. Although parents felt that they were important in supporting their adolescent, a successful PA intervention must have multiple components. Moreover, the parents noted that the intervention had a positive effect upon not only their adolescents', but also their own PA. Interventions aimed at promoting PA among adolescents should include measures to stimulate parent participation, have an empowerment approach, and preferably be school-based. PMID- 26282871 TI - Editorial to the QHW thematic cluster "Health, Physical Activity and Lifestyle". PMID- 26282872 TI - Evaluating betterment projects. AB - In the past decade Australia has experienced a series of large-scale, severe natural disasters including catastrophic bushfires, widespread and repeated flooding, and intense storms and cyclones. There appears to be a prima facie case for rebuilding damaged infrastructure to a more disaster resilient (that is, to 'betterment') standard. The purpose of this paper is to develop and illustrate a consistent and readily applied method for advancing proposals for the betterment of essential public assets, which can be used by governments at all levels to determine the net benefits of such proposals. Case study results demonstrate that betterment investments have the potential to deliver a positive economic return across a range of asset types and regions. Results, however, are highly sensitive to underlying assumptions; in particular the probability of the natural disaster affecting the infrastructure in the absence of betterment. PMID- 26282873 TI - An evaluation of the Kinect-Ed presentation, a motivating nutrition and cooking intervention for young adolescents in grades 6-8. AB - Recently, public health messaging has included having more family meals and involving young adolescents (YAs) with meal preparation to improve healthful diets and family dinner frequency (FDF). Kinect-Ed, a motivational nutrition education presentation was created to encourage YAs (grades 6-8) to help with meal preparation and ultimately improve FDF. The purpose of this study was to evaluate the Kinect-Ed presentation, with the goals of the presentation being to improve self-efficacy for cooking (SE), food preparation techniques (TECH), food preparation frequency (PREP), family meal attitudes and behaviours, and ultimately increase FDF. A sample of YAs (n = 219) from Southern Ontario, Canada, completed pre- and postpresentation surveys, measuring FDF, PREP, SE, and TECH. Kinect-Ed successfully improved participants' FDF (p < 0.01), PREP (p < 0.01), SE (p < 0.01), and TECH (<0.01). Overall, goals of the presentation were met. Encouraging YAs to help prepare meals and get involved in the kitchen may reduce the time needed from parents to prepare meals, and, in turn, allow more time for frequent family dinners. PMID- 26282874 TI - Conflict of interest and signal interference lead to the breakdown of honest signaling. AB - Animals use signals to coordinate a wide range of behaviors, from feeding offspring to predator avoidance. This poses an evolutionary problem, because individuals could potentially signal dishonestly to coerce others into behaving in ways that benefit the signaler. Theory suggests that honest signaling is favored when individuals share a common interest and signals carry reliable information. Here, we exploit the opportunities offered by bacterial signaling to test these predictions with an experimental evolution approach. We show that: (1) reduced relatedness leads to the relative breakdown of signaling, (2) signaling breaks down by the invasion of mutants that show both reduced signaling and reduced response to signal, (3) the genetic route to signaling breakdown is variable, and (4) the addition of artificial signal, to interfere with signal information, also leads to reduced signaling. Our results provide clear support for signaling theory, but we did not find evidence for previously predicted coercion at intermediate relatedness, suggesting that mechanistic details can alter the qualitative nature of specific predictions. Furthermore, populations evolved under low relatedness caused less mortality to insect hosts, showing how signal evolution in bacterial pathogens can drive the evolution of virulence in the opposite direction to that often predicted by theory. PMID- 26282875 TI - Phospholipase D2 drives mortality in sepsis by inhibiting neutrophil extracellular trap formation and down-regulating CXCR2. AB - We determined the function of phospholipase D2 (PLD2) in host defense in highly lethal mouse models of sepsis using PLD2(-/-) mice and a PLD2-specific inhibitor. PLD2 deficiency not only increases survival but also decreases vital organ damage during experimental sepsis. Production of several inflammatory cytokines (TNF, IL 1beta, IL-17, and IL-23) and the chemokine CXCL1, as well as cellular apoptosis in immune tissues, kidney, and liver, are markedly decreased in PLD2(-/-) mice. Bactericidal activity is significantly increased in PLD2(-/-) mice, which is mediated by increased neutrophil extracellular trap formation and citrullination of histone 3 through peptidylarginine deiminase activation. Recruitment of neutrophils to the lung is markedly increased in PLD2(-/-) mice. Furthermore, LPS induced induction of G protein-coupled receptor kinase 2 (GRK2) and down regulation of CXCR2 are markedly attenuated in PLD2(-/-) mice. A CXCR2-selective antagonist abolishes the protection conferred by PLD2 deficiency during experimental sepsis, suggesting that enhanced CXCR2 expression, likely driven by GRK2 down-regulation in neutrophils, promotes survival in PLD2(-/-) mice. Furthermore, adoptively transferred PLD2(-/-) neutrophils significantly protect WT recipients against sepsis-induced death compared with transferred WT neutrophils. We suggest that PLD2 in neutrophils is essential for the pathogenesis of experimental sepsis and that pharmaceutical agents that target PLD2 may prove beneficial for septic patients. PMID- 26282876 TI - Interleukin 27R regulates CD4+ T cell phenotype and impacts protective immunity during Mycobacterium tuberculosis infection. AB - CD4+ T cells mediate protection against Mycobacterium tuberculosis (Mtb); however, the phenotype of protective T cells is undefined, thereby confounding vaccination efforts. IL-27 is highly expressed during human tuberculosis (TB), and absence of IL-27R (Il27ra) specifically on T cells results in increased protection. IL-27R deficiency during chronic Mtb infection does not impact antigen-specific CD4+ T cell number but maintains programmed death-1 (PD-1), CD69, and CD127 expression while reducing T-bet and killer cell lectin-like receptor G1 (KLRG1) expression. Furthermore, T-bet haploinsufficiency results in failure to generate KLRG1+, antigen-specific CD4+ T cells, and in improved protection. T cells in Il27ra(-/-) mice accumulate preferentially in the lung parenchyma within close proximity to Mtb, and antigen-specific CD4+ T cells lacking IL-27R are intrinsically more fit than intact T cells and maintain IL-2 production. Improved fitness of IL-27R-deficient T cells is not associated with increased proliferation but with decreased expression of cell death-associated markers. Therefore, during Mtb infection, IL-27R acts intrinsically on T cells to limit protection and reduce fitness, whereas the IL-27R-deficient environment alters the phenotype and location of T cells. The significant expression of IL-27 in TB and the negative influence of IL-27R on T cell function demonstrate the pathway by which this cytokine/receptor pair is detrimental in TB. PMID- 26282879 TI - Mediating effect of stress on the association between early trauma and psychological distress in Korean college students: a cross-sectional observational study. AB - ACCESSIBLE SUMMARY: What is known on the subject? Despite the increase of studies into the predictors of psychological distress, few have attempted to address the mediation of stress in the relationship between early trauma and psychological distress. What does this paper add to existing knowledge? In this study, college students with trauma exposure before the age of 18 years reported high levels of college life stress and psychological distress. In addition, of the subcategories of early trauma, emotional abuse was most highly correlated with current stress and psychological distress. This paper confirmed the partial mediating effect of stress between early trauma and psychological distress among Korean college students. In other words, this study found a direct effect of early trauma on current psychological distress and an indirect effect of early trauma on psychological distress mediated through life stress. What are the implications for practice? Early trauma and stress should be considered when developing interventions for college students' mental health, although individuals with trauma exposure have difficulties disclosing their traumatic event. Therefore, we suggest that stress management may be easier to apply and more effective in promoting college students' mental health than trauma-focused interventions. ABSTRACT: INTRODUCTION: Research has shown that early trauma and stress may affect current psychological distress. However, few studies have attempted to address the mediation of stress between early trauma and psychological distress. AIM: This cross-sectional observational study aimed to examine the mediating effects of stress on the association between early trauma and psychological distress in Korean college students. METHOD: Participants included 216 college students (51.4% male) who completed self-report questionnaires assessing early trauma, college life stress, and psychological distress. RESULTS: Early trauma, stress, and psychological distress were significantly correlated. Of the subcategories of early trauma, emotional abuse was most highly correlated with stress and psychological distress. The bootstrapping results indicate that stress is a partial mediator between early trauma and psychological distress after controlling for covariates including socioeconomic status, habitation status, and gender. DISCUSSION: The results imply that both early trauma and stress should be considered when developing interventions for college students' mental health. However, individuals with trauma exposure tend to have difficulties disclosing their traumatic event. Therefore, we suggest that stress management may be more feasible and effective in promoting college students' mental health than trauma focused interventions. PMID- 26282877 TI - Kindlin-3-mediated integrin adhesion is dispensable for quiescent but essential for activated hematopoietic stem cells. AB - Hematopoietic stem cells (HSCs) generate highly dividing hematopoietic progenitor cells (HPCs), which produce all blood cell lineages. HSCs are usually quiescent, retained by integrins in specific niches, and become activated when the pools of HPCs decrease. We report that Kindlin-3-mediated integrin activation controls homing of HSCs to the bone marrow (BM) and the retention of activated HSCs and HPCs but not of quiescent HSCs in their BM niches. Consequently, Kindlin-3 deficient HSCs enter quiescence and remain in the BM when cotransplanted with wild-type hematopoietic stem and progenitor cells (HSPCs), whereas they are hyperactivated and lost in the circulation when wild-type HSPCs are absent, leading to their exhaustion and reduced survival of recipients. The accumulation of HSPCs in the circulation of leukocyte adhesion deficiency type III patients, who lack Kindlin-3, underlines the conserved functions of Kindlin-3 in man and the importance of our findings for human disease. PMID- 26282878 TI - The role of Fc-FcgammaR interactions in IgG-mediated microbial neutralization. AB - Antibodies are bifunctional molecules, containing a variable Fab domain that mediates binding specificity and a constant Fc domain that bridges antibody coated targets with FcgammaR-expressing cells that mediate effector functions. Although traditional mechanisms of antibody-mediated neutralization of microbes have been largely thought to result from Fab-antigen interactions, recent studies suggest that recruitment of FcgammaR-expressing effector cells by antibodies is a major in vivo mechanism of antibody-mediated protection from infection. In this article, we review FcgammaR biology, compare mammalian FcgammaR families, and summarize recent evidence demonstrating the crucial role that Fc-FcgammaR interactions play during in vivo protection from infection. PMID- 26282881 TI - Insertion of N2 into the Channels of AFI Zeolite under High Pressure. AB - We present an experimental study of a new hybrid material where nitrogen is encapsulated in the channels of porous zeolite AlPO4-5 (AFI) single crystals by a high-pressure method. The high-pressure behavior of nitrogen confined inside the AFI nano-channels is then investigated by Raman spectroscopy up to 44 GPa. Under pressure, the Raman modes of confined nitrogen show behaviors different from those of the bulk nitrogen. After the return to atmospheric pressure, it is demonstrated that non-gaseous nitrogen can be effectively stabilized by being confined inside the intact AFI sample. This result provides new insight into nitrogen capture and storage technologies. PMID- 26282880 TI - Gender specific effect of LIPC C-514T polymorphism on obesity and relationship with plasma lipid levels in Chinese children. AB - Hepatic lipase (LIPC) is a key rate-limiting enzyme in lipoprotein catabolism pathways involved in the development of obesity. The C-514T polymorphism in the promoter region is associated with decreased LIPC activity. We performed a case controlled study (850 obese children and 2119 controls) and evaluated the association between LIPC C-514T polymorphism, obesity and plasma lipid profile in Chinese children and adolescents. Additionally, we conducted a meta-analysis of all results from published studies as well as our own data. A significant association between the polymorphism and obesity is observed in boys (P = 0.042), but not in girls. And we observed a significant relationship of the polymorphism with total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) independent of obesity in boys. The T allele carriers have higher levels of low density lipoprotein cholesterol (LDL-C) in obese boys, and triglyceride (TG), TC and LDL-C in non-obese girls (all P < 0.05). In the meta-analysis, under dominant model the T allele increased body mass index (BMI) level in boys, while it decreased BMI in girls, and increased the levels of TC both in the overall and subgroups, TG and HDL-C in the overall and boys, and LDL-C in the overall (all P < 0.05). Our results suggest that the T allele might carry an increased risk of obesity in Chinese boys. The meta-analysis suggests that T allele acts as a risk allele for higher BMI levels in male childhood, while it is a protective allele in female childhood. And the polymorphism is associated with the levels of plasma lipids, which may be modulated by obesity and gender. PMID- 26282882 TI - Ingenane-type diterpene compounds from Euphorbia kansui modulate IFN-gamma production through NF-kappaB activation. AB - BACKGROUND: Euphorbia kansui, a traditional medical herb, has been shown to have anti-tumour and anti-viral activities. Previously, we have reported that E. kansui increases interferon-gamma (IFN-gamma) production in natural killer (NK) cells. However, it is not clear how E. kansui regulates IFN-gamma secretion by NK cells. RESULTS: In this study, E. kansui was separated into six individual compounds from the same chloroform fraction so that the activity of each compound could be compared. E. kansui compounds induced IFN-gamma secretion through the phosphorylation of protein kinase D and IkappaB kinase pathways. Furthermore, E. kansui compounds activated the translocation of p65, a sub-unit of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB), to the nucleus and induced NF-kappaB at the transcriptional level. CONCLUSION: These findings suggest that E. kansui enhances IFN-gamma secretion through the NF-kappaB pathway in NK cells. (c) 2015 Society of Chemical Industry. PMID- 26282883 TI - Cryopreservation of cells: FT-IR monitoring of lipid membrane at freeze-thaw cycles. AB - In the present study, FTIR spectroscopy was used to monitor the freeze-thaw cycle of two cellular lines (HuDe and Jurkat) suspended in three different media: phosphate buffer solution (PBS); dimethylsulfoxide (DMSO)/PBS solution at 0.1 DMSO molar fraction; and CryoSure (0.1 DMSO molar fraction PBS solution+dextran 5% w/v) solution. The Trypan Blue test was also applied before freezing and after thawing each cell sample to estimate the recovery of membrane integrity after thermal treatment, and correlate this datum with spectroscopic results. By following the temperature evolution of two different spectral components (the libration and bending combination mode nuc(H2O) at 2000-2500 cm(-1), and the methylene symmetric stretching vibration nusym(CH2) at about 2850 cm(-1)) in the 120/28 degrees C range, we evidenced the main transition of lipid membrane in connection with cell dehydration, as induced by ice formation in the extracellular medium. In particular, in DMSO/PBS and CryoSure samples we observed a transition to a more rigid state of the lipid membrane together with an increased amount of non-freezable water in the extracellular medium; these results are connected to the role of DMSO as a cryoprotective agent irrespective of the nature of cell type. PMID- 26282884 TI - Cholesteryl-ester transfer protein (CETP): A Kupffer cell marker linking hepatic inflammation with atherogenic dyslipidemia? PMID- 26282886 TI - CXCL12 catches T-ALL at the entrance of the bone marrow. AB - A fraction of patients with T-cell acute lymphoblastic leukemias (T-ALLs) relapse and have a dismal prognosis. Two recent papers in Cancer Cell reveal that endothelial cell-derived CXCL12 is essential for bone marrow involvement and tumor progression in T-ALL patients, suggesting that this chemokine axis presents a potential therapeutic target for the treatment of T-ALL. PMID- 26282887 TI - Does continuous partial attention offer a new understanding of the required vigilance and associated stress for parents of children with complex needs? PMID- 26282885 TI - Tissue instruction for migration and retention of TRM cells. AB - During infection, a subset of effector T cells seeds the lymphoid and non lymphoid tissues and gives rise to tissue-resident memory T cells (TRM). Recent findings have provided insight into the molecular and cellular mechanisms underlying tissue instruction of TRM cell homing, as well as the programs involved in their retention and maintenance. We review these findings here, highlighting both common features and distinctions between CD4 TRM and CD8 TRM cells. In this context we examine the role of memory lymphocyte clusters (MLCs), and propose that the MLCs serve as an immediate response center consisting of TRM cells on standby, capable of detecting incoming pathogens and mounting robust local immune responses to contain and limit the spread of infectious agents. PMID- 26282888 TI - Recovery of copper from PVC multiwire cable waste by steam gasification. AB - Screened multiwire, PVC insulated tinned copper cable was gasified with steam at high temperature (HTSG) under atmospheric pressure for recovery of cooper. Gases from the process were additionally equilibrated at 850 degrees C on the bed of calcined clay granules and more than 98% of C+H content in the cable was transformed to non-condensing species. Granules prepared from local clay were generally resistant for chlorination, there was also almost no deposition of metals, Cu and Sn, on the catalytic bed. It was found that 28% of chlorine reacted to form CaCl2, 71% was retained in aqueous condensate and only 0.6% was absorbed in alkaline scrubber. More than 99% of calcium existed in the process solid residue as a mixture of calcium chloride and calcium oxide/hydroxide. PVC and other hydrocarbon constituents were completely removed from the cable sample. Copper was preserved in original form and volatilization of copper species appeared insignificant. Tin was alloying with copper and its volatilization was less than 1%. Fractionation and speciation of metals, chlorine and calcium were discussed on the basis of equilibrium model calculated with HSC Chemistry software. High temperature steam gasification prevents direct use of the air and steam/water is in the process simultaneously gaseous carrier and reagent, which may be recycled together with hydrocarbon condensates. PMID- 26282890 TI - The impact of covariance misspecification in group-based trajectory models for longitudinal data with non-stationary covariance structure. AB - One purpose of a longitudinal study is to gain a better understanding of how an outcome of interest changes among a given population over time. In what follows, a trajectory will be taken to mean the series of measurements of the outcome variable for an individual. Group-based trajectory modelling methods seek to identify subgroups of trajectories within a population, such that trajectories that are grouped together are more similar to each other than to trajectories in distinct groups. Group-based trajectory models generally assume a certain structure in the covariances between measurements, for example conditional independence, homogeneous variance between groups or stationary variance over time. Violations of these assumptions could be expected to result in poor model performance. We used simulation to investigate the effect of covariance misspecification on misclassification of trajectories in commonly used models under a range of scenarios. To do this we defined a measure of performance relative to the ideal Bayesian correct classification rate. We found that the more complex models generally performed better over a range of scenarios. In particular, incorrectly specified covariance matrices could significantly bias the results but using models with a correct but more complicated than necessary covariance matrix incurred little cost. PMID- 26282889 TI - A review of instrumental variable estimators for Mendelian randomization. AB - Instrumental variable analysis is an approach for obtaining causal inferences on the effect of an exposure (risk factor) on an outcome from observational data. It has gained in popularity over the past decade with the use of genetic variants as instrumental variables, known as Mendelian randomization. An instrumental variable is associated with the exposure, but not associated with any confounder of the exposure-outcome association, nor is there any causal pathway from the instrumental variable to the outcome other than via the exposure. Under the assumption that a single instrumental variable or a set of instrumental variables for the exposure is available, the causal effect of the exposure on the outcome can be estimated. There are several methods available for instrumental variable estimation; we consider the ratio method, two-stage methods, likelihood-based methods, and semi-parametric methods. Techniques for obtaining statistical inferences and confidence intervals are presented. The statistical properties of estimates from these methods are compared, and practical advice is given about choosing a suitable analysis method. In particular, bias and coverage properties of estimators are considered, especially with weak instruments. Settings particularly relevant to Mendelian randomization are prioritized in the paper, notably the scenario of a continuous exposure and a continuous or binary outcome. PMID- 26282891 TI - Crucial role of the orexin-B C-terminus in the induction of OX1 receptor-mediated apoptosis: analysis by alanine scanning, molecular modelling and site-directed mutagenesis. AB - BACKGROUND AND PURPOSE: Orexins (A and B) are hypothalamic peptides that interact with OX1 and OX2 receptors and are involved in the sleep/wake cycle. We previously demonstrated that OX1 receptors are highly expressed in colon cancer tumours and colonic cancer cell lines where orexins induce apoptosis and inhibit tumour growth in preclinical animal models. The present study explored the structure-function relationships of orexin-B and OX1 receptors. EXPERIMENTAL APPROACH: The contribution of all orexin-B residues in orexin-B-induced apoptosis was investigated by alanine scanning. To determine which OX1 receptor domains are involved in orexin-B binding and apoptosis, a 3D model of OX1 receptor docked to the orexin-B C-terminus (AA-20-28) was developed. Substitution of residues present in OX1 receptor transmembrane (TM) domains by site-directed mutagenesis was performed. KEY RESULTS: Alanine substitution of orexin-B residues, L(11) , L(15) , A(22) , G(24) , I(25) , L(26) and M(28) , altered orexin-B's binding affinity. Substitution of these residues and of the Q(16) , A(17) , S(18) , N(20) and T(27) residues inhibited apoptosis in CHO-S-OX1 receptor cells. The K(120) , P(123) , Y(124) , N(318) , K(321) , F(340) , T(341) , H(344) and W(345) residues localized in TM2, TM3, TM6 and TM7 of OX1 receptors were shown to play a role in orexin-B recognition and orexin-B/OX1 receptor-induced apoptosis. CONCLUSIONS AND IMPLICATIONS: The C-terminus of orexin-B (i) plays an important role in its pro apoptotic effect; and (ii) interacts with some residues localized in the OX1 receptor TM. This study defines the structure-function relationship for orexin-B recognition by human OX1 receptors and orexin-B/OX1 receptor-induced apoptosis, an important step for the future development of new agonist molecules. PMID- 26282892 TI - Demographic risk factors impacting timely radiation therapy completion after breast conserving surgery. AB - BACKGROUND: Radiotherapy completion (RTC) is critical to successful breast conserving treatment. Our aim was to identify patient groups at greatest risk of not achieving timely radiotherapy completion (TRTC) in an urban setting. METHODS: This observational cohort study used hospital registry data from 2004 to 2010 for female stage I and II breast conserving treatment patients to assess predictors of RTC and TRTC, defined as RTC of 35 to 49 days. RESULTS: Two hundred sixty-one patients were analyzed. There was no difference in mean days to RTC by ethnicity (black 46.8, white 46.4, Hispanic 48.1 days, P = .75) or total RTC (black 88.2%, white 97.9%, Hispanic 93.3%, P = .09). However, a substantial difference was seen in TRTC by ethnicity (black 51.8%, white 79.2%, Hispanic 57.8%, P = .03). Multivariate logistic regression analysis of failure to achieve TRTC found associations with black race (odds ratio [OR] 2.67), Medicare (OR 3.46), Medicaid (OR 2.19), and age less than 50 years (OR 4.13). CONCLUSIONS: This study demonstrates high overall percentage RTC but demonstrates disparities in TRTC. Those at greatest risk of unsuccessful TRTC were younger, Medicare or Medicaid insured, and black race. PMID- 26282893 TI - Epigenetic modification maintains intrinsic limb-cell identity in Xenopus limb bud regeneration. AB - Many amphibians can regenerate limbs, even in adulthood. If a limb is amputated, the stump generates a blastema that makes a complete, new limb in a process similar to developmental morphogenesis. The blastema is thought to inherit its limb-patterning properties from cells in the stump, and it retains the information despite changes in morphology, gene expression, and differentiation states required by limb regeneration. We hypothesized that these cellular properties are maintained as epigenetic memory through histone modifications. To test this hypothesis, we analyzed genome-wide histone modifications in Xenopus limb bud regeneration. The trimethylation of histone H3 at lysine 4 (H3K4me3) is closely related to an open chromatin structure that allows transcription factors access to genes, whereas the trimethylation of histone H3 at lysine 27 (H3K27me3) is related to a closed chromatin state that blocks the access of transcription factors. We compared these two modification profiles by high-throughput sequencing of samples prepared from the intact limb bud and the regenerative blastema by chromatin immunoprecipitation. For many developmental genes, histone modifications at the transcription start site were the same in the limb bud and the blastema, were stable during regeneration, and corresponded well to limb properties. These results support our hypothesis that histone modifications function as a heritable cellular memory to maintain limb cell properties, despite dynamic changes in gene expression during limb bud regeneration in Xenopus. PMID- 26282894 TI - H(+)/K(+) ATPase activity is required for biomineralization in sea urchin embryos. AB - The bioelectrical signatures associated with regeneration, wound healing, development, and cancer are changes in the polarization state of the cell that persist over long durations, and are mediated by ion channel activity. To identify physiologically relevant bioelectrical changes that occur during normal development of the sea urchin Lytechinus variegatus, we tested a range of ion channel inhibitors, and thereby identified SCH28080, a chemical inhibitor of the H(+)/K(+) ATPase (HKA), as an inhibitor of skeletogenesis. In sea urchin embryos, the primary mesodermal lineage, the PMCs, produce biomineral in response to signals from the ectoderm. However, in SCH28080-treated embryos, aside from randomization of the left-right axis, the ectoderm is normally specified and differentiated, indicating that the block to skeletogenesis observed in SCH28080 treated embryos is PMC-specific. HKA inhibition did not interfere with PMC specification, and was sufficient to block continuing biomineralization when embryos were treated with SCH28080 after the initiation of skeletogenesis, indicating that HKA activity is continuously required during biomineralization. Ion concentrations and voltage potential were abnormal in the PMCs in SCH28080 treated embryos, suggesting that these bioelectrical abnormalities prevent biomineralization. Our results indicate that this effect is due to the inhibition of amorphous calcium carbonate precipitation within PMC vesicles. PMID- 26282895 TI - Stoichiometry for alpha-bungarotoxin block of alpha7 acetylcholine receptors. AB - alpha-Bungarotoxin (alpha-Btx) binds to the five agonist binding sites on the homopentameric alpha7-acetylcholine receptor, yet the number of bound alpha-Btx molecules required to prevent agonist-induced channel opening remains unknown. To determine the stoichiometry for alpha-Btx blockade, we generate receptors comprised of wild-type and alpha-Btx-resistant subunits, tag one of the subunit types with conductance mutations to report subunit stoichiometry, and following incubation with alpha-Btx, monitor opening of individual receptor channels with defined subunit stoichiometry. We find that a single alpha-Btx-sensitive subunit confers nearly maximal suppression of channel opening, despite four binding sites remaining unoccupied by alpha-Btx and accessible to the agonist. Given structural evidence that alpha-Btx locks the agonist binding site in an inactive conformation, we conclude that the dominant mechanism of antagonism is non competitive, originating from conformational arrest of the binding sites, and that the five alpha7 subunits are interdependent and maintain conformational symmetry in the open channel state. PMID- 26282896 TI - Broadband zero-backward and near-zero-forward scattering by metallo-dielectric core-shell nanoparticles. AB - Efficient control of optical radiation at subwavelength scales plays important roles for various applications. Dielectric nanoparticles or dielectric shells with a large refractive index of n ~ 3-4, which are only achievable for limited semiconductors, are involved in most designs so far to control the scattering by overlapping the electric and magnetic dipolar modes of the same magnitude. Here we propose a new mechanism based on the interplay between dipolar and quadrupolar resonances of different amplitudes, both magnetic and electric, to suppress the backward scattering or the forward scattering by using metallo-dielectric core shell nanoparticles with a dielectric shell layer having a refractive index of n = 2.0. We demonstrate that broadband zero-backward or near-zero-forward scattering can be achieved by optimizing the structural parameters. We also demonstrate that the core-shell nanoparticles with identical dielectric shells but metal cores with various sizes are able to suppress the backward or forward scattering at the same wavelength, thus revealing a large tolerance to fabrication errors induced by the size distributions in the metal cores. These features make the proposed core-shell nanoparticles beyond the dipole limit more easily realized in practical experiments. PMID- 26282897 TI - Assessment of Adverse Drug Reaction Due to Cancer Chemotherapy in a Teaching Oncology Hospital in Isfahan, Central of Iran. AB - INTRODUCTION: Adverse Drug Reactions (ADRs) are common in hospitalized oncology patients. The kinds of ADRs experienced by cancer patients are varied. Therefore, the identification of appropriate manner in order to prevent ADRs may improve patient outcome. AIMS: The present study evaluated the incidence, frequency and common types of adverse drug reactions among hospitalized oncology patients. METHODS: Patients hospitalized at a university oncology center (children and adult) during the calendar year 2012 were randomly selected. Data were collected by reviewing of medical records. The outcome measures included the incidence of observed ADRs and ADR-related admissions and achieving strategies to prevent the emergence of chemotherapy side effects. RESULTS: ADRs frequently occurred in the age group less than 20 years (22%). Prevalence of leukemia (27%), colon cancer (16.5%) and breast cancer (14%) was higher in our region. Most ADRs were recorded in patients receiving cisplatin (44%), doxorubicin (24%) and 5-fluouracil (20%) as chemotherapy. The most frequently observed ADRs were nauseavomiting, neutropenia and constipation in both pediatric and adult population. CONCLUSION: This study shows that ADRs occur more frequently in the pediatric group compared to adults. Therefore, optimum use of preventative strategy program may contribute to reducing the incidence and severity of ADRs especially in this group. PMID- 26282898 TI - Prognostic factors after R0 resection of colorectal cancer liver metastases: A systematic review and pooled-analysis. AB - BACKGROUND: Prognostic variables associated with outcome after curative (R0) Resection of Colorectal Cancer (CRC) liver metastases are paramount in identifying high-risk patients after surgery. The aim of this study was to identify risk factors related to Overall Survival (OS) after R0 resection of CRC liver metastases. METHODS: A literature search on prognostic factors after resection of liver metastases was performed. Studies were eligible if covariates associated with OS were reported in patients with R0 resected CRC liver metastases. Independent prognostic factors associated with OS were identified using multivariate analysis. RESULTS: Twenty-four publications with a total of 4855 patients were eligible. In multivariate analyses, a disease-free interval < 12 months (hazard ratio [HR] 1.47, P = 0.0002), the size of the largest metastasis (HR 1.56, P < 0.0001), the total number of metastases (HR 1.73, P < 0.00001), a primary tumor with node-positive status (HR 1.56, P = 0.002), a rectal primary tumor (HR 1.48, P < 0.00001), a high carcinoembryonic antigen level (HR 1.49, P = 0.02), a high tumor grade (HR 2.42, P < 0.00001), and extrahepatic disease (HR 2.03, P < 0.00001) were associated with an increased risk of death after R0 resection of CRC liver metastases in at least 3 studies. CONCLUSION: We identified 9 clinicopathological prognostic factors that could help identify high-risk patients and guide further treatment and follow up decisions. In particular burden of liver and extrahepatic metastases and grade are those associated with a higher risk of death. PMID- 26282899 TI - Irrigation with N,N-dichloro-2,2-dimethyltaurine (NVC-422) in a citrate buffer maintains urinary catheter patency in vitro and prevents encrustation by Proteus mirabilis. AB - Long-term use of indwelling urinary catheters can lead to urinary tract infections and loss of catheter patency due to encrustation and blockage. Encrustation of urinary catheters is due to formation of crystalline biofilms by urease-producing microorganisms such as Proteus mirabilis. An in vitro catheter biofilm model (CBM) was used to evaluate current methods for maintaining urinary catheter patency. We compared antimicrobial-coated urinary Foley catheters, with both available catheter irrigation solutions and investigational solutions containing NVC-422 (N,N-dichloro-2,2-dimethyltaurine; a novel broad-spectrum antimicrobial). Inoculation of the CBM reactor with 10(8) colony-forming units of P. mirabilis resulted in crystalline biofilm formation in catheters by 48 h and blockage of catheters within 5 days. Silver hydrogel or nitrofurazone-coated catheters did not extend the duration of catheter patency. Catheters irrigated daily with commercially available solutions such as 0.25 % acetic acid and isotonic saline blocked at the same rate as untreated catheters. Daily irrigations of catheters with 0.2 % NVC-422 in 10 mM acetate-buffered saline pH 4 or Renacidin maintained catheter patency throughout 10-day studies, but P. mirabilis colonization of the CBM remained. In contrast, 0.2 % NVC-422 in citrate buffer (6.6 % citric acid at pH 3.8) resulted in an irrigation solution that not only maintained catheter patency for 10 days but also completely eradicated the P. mirabilis biofilm within one treatment day. These data suggest that an irrigation solution containing the rapidly bactericidal antimicrobial NVC-422 in combination with citric acid to permeabilize crystalline biofilm may significantly enhance catheter patency versus other approved irrigation solutions and antimicrobial-coated catheters. PMID- 26282900 TI - Nasopharyngeal carcinoma with intracranial extension in the era of intensity modulated radiotherapy: case-control study using propensity score matching method. AB - The objective of the study was to evaluate long-term survival outcomes and toxicity of T4 classification nasopharyngeal carcinoma (NPC) with intracranial extension (IE group) or without intracranial extension (non-IE group) after intensity-modulated radiotherapy (IMRT) using the propensity score matching method. After generating propensity scores given the covariates of age, sex, N classification, and concurrent chemotherapy, 132 patients in each group were matched. The 5-year local failure-free survival rate and the 5-year overall survival rate in the IE group were lower than the patients in the non-IE group (74.6 vs. 88.9 %, p = .008; 51.1 vs. 71.9 %, p = .005). Grade 2 hypothyroidism was more common in the IE group (13.2 vs. 3.4 %, p = .029). For patients with T4 classification NPC after IMRT, patients with intracranial extension need more attention to the thyroid gland function and are more likely to experience local failure and death than patients without intracranial extension. PMID- 26282901 TI - Long-term quality of life after endoscopic removal of sinonasal inverted papillomas: a 6-year cohort analysis in a tertiary academic hospital. AB - Inverted papillomas may affect the (para)nasal cavity. While some of these papillomas can undergo malignant transformation, others grow slowly and cause few if any symptoms. An endoscopic approach is seen as providing a balance between the greatest removal possible and avoiding unnecessary morbidity. However, the actual long-term quality of life of patients having undergone surgery for inverted papillomas has never been studied. Our primary aim is to assess the long term sequelae and the quality of life of patients after endoscopic surgery of sinonasal inverted papillomas. The secondary aim is to establish which nasal symptoms, if any, are the most prevalent before and after surgery. We used the SNOT-22 questionnaire to assess the quality of life of patients who had undergone endoscopic surgery for sinonasal inverted papillomas between 2000 and 2011. Twenty-seven out of 34 patients returned the questionnaire (79 % response rate). Median follow-up was 6 years (range 1-10). Mean age was 58.9 years (range 40-85). Median SNOT-22 score was 12, while the most frequent postoperative symptom was the need to blow the nose (18 patients) and the most frequent preoperative symptom was nasal obstruction. Patients after endoscopic removal of sinonasal inverted papillomas return to an almost normal quality of life, as measured by the disease-specific questionnaire SNOT-22. The most frequent symptom was the need to blow the nose. PMID- 26282902 TI - Expression of inflammasome-related genes in bladder cancer and their association with cytokeratin 20 messenger RNA. AB - BACKGROUND: Inflammation plays a crucial role in different stages of cancer development and has long been associated with various types of cancer. Strong associations between dysregulated inflammasome activity and human heritable and acquired inflammatory diseases highlight the importance of this pathway in the immune response. The inflammasome is a large complex of NOD-like receptors called NLRs and drives growth and progression of different tumors. The aim of the present study was the characterization of some NLR genes, NLRP3, NLRP4, NLRP9, and NAIP, in urine sediment of patients with bladder cancer. Cytokeratin 20 and survivin were used as confirmed markers of bladder cancer. BASIC PROCEDURES: For this study, 3 groups of subjects were considered: patients harboring bladder cancer, subjects affected by bladder inflammation (CTR1), and healthy subjects (CTR0). Total RNA was extracted from urine sediments and resulting complementary DNA was used for amplification by real-time polymerase chain reaction. Results were stratified according to tumor stage, grade, and risk of progression and recurrence. MAIN FINDINGS: The expression of cytokeratin 20 was always significantly higher in patients with bladder cancer when compared with that in both the tumor-free groups. NLRP3, NLRP4, NLRP9, and NAIP were overexpressed in patients with BCa when compared with that in CTR0. Stratification according to tumor stage, grade, and risk of recurrence and progression showed NLRP up regulations in patients with early-stage cancer. NAIP was overexpressed in high risk patients in comparison to CTR0 and in high-grade patients compared with CTR0 and CTR1. PRINCIPAL CONCLUSIONS: These data are relevant to demonstrate the role of inflammasome in urothelial carcinoma, making NLR genes in urine sediment potential candidates for bladder cancer diagnosis. PMID- 26282903 TI - Novel P-TEN-induced putative kinase 1 (PINK1) variant in Indian Parkinson's disease patient. AB - Loss-of-function mutation in PINK1 is known for causing autosomal recessive early onset Parkinsonism accounting approximately 6.5% of PD cases. Recently, PINK1 has also been shown to cause Parkinson's disease (PD) in eastern India. Present study is aimed to see its contribution in north-Indian PD patients. A total of 106 PD patients and 60 ethnically matched healthy controls were included in the study. All the patients were screened for mutation in PINK1 by direct DNA sequence analysis of the PCR amplicons covering all exons and exon-intron boundaries. Identified novel variant was reconfirmed by DNA sequencing of 10 randomly selected TA clones containing the variant amplicon. In vitro functional assay of the mutant protein was performed by transfecting COS-7 cell line with wild type and mutant (created by site-directed-mutagenesis) cDNA construct of PINK1 fused to N' terminal GFP followed by western blot analysis. Two potentially pathogenic, one being novel (p.Q267X) and 6 other apparently non-pathogenic variants were identified. Western blot analysis reveals production of truncated PINK1 fusion protein of ~55kDa in p.Q267X mutant instead of 82/93kDa of wild type PINK1 fusion protein (molecular weight of GFP is ~27kDa). Our study concludes that PINK1 variants are prevalent for causing Parkinson's disease (PD) in India, as revealed by the occurrence of 1.8% (2/106) in PD patients from north Indian population. The novel homozygous variant of PINK1 (c.799C>T) reported here is the plausible cause for disease manifestation in this patient. Future study, however, would be helpful to understand the functional mechanism how this premature PINK1 protein (p.Q267X) responds to cellular stress leading to the PD pathophysiology. PMID- 26282904 TI - Effects of curcumin on TTX-R sodium currents of dorsal root ganglion neurons in type 2 diabetic rats with diabetic neuropathic pain. AB - Type 2 diabetic mellitus (T2DM) has reached pandemic status and shows no signs of abatement. Diabetic neuropathic pain (DNP) is generally considered to be one of the most common complications of T2DM, which is also recognized as one of the most difficult types of pain to treat. As one kind of peripheral neuropathic pain, DNP manifests typical chronic neuralgia symptoms, including hyperalgesia, allodynia, autotomy, and so on. The injured dorsal root ganglion (DRG) is considered as the first stage of the sensory pathway impairment, whose neurons display increased frequency of action potential generation and increased spontaneous activities. These are mainly due to the changed properties of voltage gated sodium channels (VGSCs) and the increased sodium currents, especially TTX-R sodium currents. Curcumin, one of the most important phytochemicals from turmeric, has been demonstrated to effectively prevent and/or ameliorate diabetic mellitus and its complications including DNP. The present study demonstrates that the TTX-R sodium currents of small-sized DRG neurons isolated from DNP rats are significantly increased. Such abnormality can be efficaciously ameliorated by curcumin. PMID- 26282905 TI - Comparison of Secondary and Primary Thyroid Cancers: Patient Characteristics and Postoperative Outcomes: A Cross-Sectional Analysis of Patients with Primary and Secondary Thyroid Cancers. AB - BACKGROUND: Secondary thyroid cancer is believed to lead to a more aggressive clinical course than primary thyroid cancer. We aim to examine the difference between primary and secondary thyroid cancer in terms of patient characteristics and perioperative outcomes at the national level. METHODS: A cross-sectional study utilizing the Nationwide Inpatient Sample database for 2003-2010 was merged with County Health Rankings Data. International Classification of Diseases, Ninth Revision (ICD-9) codes were used to identify adult patients with thyroid cancer. RESULTS: A total of 21,581 discharge records were included. Overall, 16,625 (77.0 %) patients had primary cancer, while the rest (23.0 %) had secondary cancer. Younger (<45 years) and older (>65 years) patients, males, and those of White or Hispanic background were more likely to have secondary cancers (p < 0.05 each). The prevalence of secondary cancer was higher in communities of low health risk (24.0 % vs. 21.1 %; p < 0.024). Secondary cancer was more likely to be managed by total thyroidectomy (odds ratio [OR] 2.40, 95 % CI 2.12-2.73) and to require additional radical neck dissection (OR 12.51, 95 % CI 10.98-14.25). Patients with secondary thyroid cancers were at higher risk of postoperative complications (p < 0.01 each). The cost of secondary cancer management was significantly higher than primary cancer (US$12,449.00 +/- 302.07 vs. US$7848.12 +/- 149.05; p < 0.001). However, compared with intermediate-volume surgeons, the complication risk was lower for high-volume (OR 0.47, 95 % CI 0.24-0.92; p = 0.026). CONCLUSIONS: Secondary thyroid cancer is associated with a higher risk of perioperative complications and higher cost and distinct demographic profile. Patients managed by higher-volume surgeons were less likely to experience disadvantageous outcomes. PMID- 26282906 TI - Palliative Care Training in Surgical Oncology and Hepatobiliary Fellowships: A National Survey of Program Directors. AB - BACKGROUND: Despite previous literature affirming the importance of palliative care training in surgery, there is scarce literature about the readiness of Surgical Oncology and hepatopancreaticobiliary (HPB) fellows to provide such care. We performed the first nationally representative study of surgical fellowship program directors' assessment of palliative care education. The aim was to capture attitudes about the perception of palliative care and disparity between technical/clinical education and palliative care training. METHODS: A survey originally used to assess surgical oncology and HPB surgery fellows' training in palliative care, was modified and sent to Program Directors of respective fellowships. The final survey consisted of 22 items and was completed online. RESULTS: Surveys were completed by 28 fellowship programs (70 % response rate). Only 60 % offered any formal teaching in pain management, delivering bad news or discussion about prognosis. Fifty-eight percent offered formal training in basic communication skills and 43 % training in conducting family conferences. Resources were available, with 100 % of the programs having a palliative care consultation service, 42 % having a faculty member with recognized clinical interest/expertise in palliative care, and 35 % having a faculty member board certified in Hospice and Palliative Medicine. CONCLUSIONS: Our data shows HPB and surgical oncology fellowship programs are providing insufficient education and assessment in palliative care. This is not due to a shortage of faculty, palliative care resources, or teaching opportunities. Greater focus one valuation and development of strategies for teaching palliative care in surgical fellowships are needed. PMID- 26282908 TI - Whole Body Metabolic Tumor Volume and Total Lesion Glycolysis Predict Survival in Patients with Adrenocortical Carcinoma. AB - BACKGROUND: Adrenocortical carcinoma (ACC) is a rare but lethal malignancy with few reliable prognostic markers. FDG-PET metabolic parameters have been shown to predict survival in several cancers. The objective was to determine if metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) could serve as prognostic markers in patients with ACC. METHODS: A total of 30 patients with ACC prospectively underwent 18F-FDG PET/CT prior to treatment. Whole body MTV, TLG, and SUVmax were measured by a semiautomatic method. A median cutoff was used to determine an association with overall survival (OS) from the time of 18F-FDG PET/CT by the Kaplan-Meier method. RESULTS: Patients with high whole body MTV (>87.0 mL),TLG (>229.4 SUVlbm*mL), or SUVmax (>8.9 SUV) had a worse OS compared with those with low whole body MTV (median OS, 24 vs 45.1 months, p < .01), TLG (median OS, 24 vs 40.3 months, p < .005), or SUVmax (median OS, 23.7 vs 35.5 months, p < .02). In patients who had operable disease (n = 23), high whole body MTV (>87.0 mL) and TLG (>229.4 SUVlbm*mL) had a worse OS compared with those with low whole body MTV (median OS, 25.1 vs 45.1 months, p < .05) and TLG (median OS, 25.1 vs 40.3 months, p < .05), but a high SUVmax (>8.9 SUV) was not associated with worse OS (p = .11). CONCLUSIONS: Patients with ACC and a high whole body MTV, TLG, and SUVmax have a worse prognosis and OS. Measurement of whole body MTV and TLG may be helpful for guiding therapy for patients with ACC. PMID- 26282907 TI - Curative Resection of Adrenocortical Carcinoma: Rates and Patterns of Postoperative Recurrence. AB - BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignancy. The aim of this study was to determine the incidence and patterns of recurrence after curative intent surgery for ACC. METHODS: Patients who underwent curative-intent resection for ACC between 1993 and 2014 were identified from 13 academic institutions participating in the United States ACC study group. Patients with metastasis or an R2 margin were excluded. Patterns and rates of recurrence were determined and classified as locoregional and distant recurrence. RESULTS: A total of 180 patients with a median age of 52 years (interquartile range 43-61) were identified. Most patients underwent open surgery (n = 111, 64.5 %) and had an R0 resection margin (n = 117, 75.0 %). At last follow-up, 116 patients (64.4 %) had experienced recurrence (locoregional only, n = 41, 36.3 %; distant only, n = 51, 45.1 %; locoregional and distant, n = 21, 18.6 %). Median time to recurrence was 18.8 months. Several factors were associated with locoregional recurrence, including left-sided ACC location (odds ratio [OR] 2.71, 95 % confidence interval [CI] 1.06-6.89) and T3/T4 disease (reference T1/T2, OR 3.04, 95 % CI 1.19-7.80) (both p < 0.05). Distant recurrence was associated with larger tumor size (OR 1.11, 95 % CI 1.01-1.24) and T3/T4 disease (reference T1/T2, OR 5.23, 95 % CI 1.70-16.10) (both p < 0.05). Patients with combined locoregional and distant recurrence had worse survival (3- and 5-year survival: 39.5, 19.7 %) versus patients with distant-only (3- and 5-year survival 55.1, 43.3 %) or locoregional only recurrence (3- and 5-year survival 81.4, 64.1 %) (p = 0.01). CONCLUSIONS: Nearly two-thirds of patients experienced disease recurrence after resection of ACC. Although a subset of patients experienced recurrence with locoregional disease only, many patients experienced recurrence with distant disease as a component of recurrence and had a poor prognosis. PMID- 26282909 TI - Peroxidase induced oligo-tyrosine cross-links during polymerization of alpha lactalbumin. AB - Horseradish peroxidase (HRP) induced cross-linking of proteins has been reported to proceed through formation of di-tyrosine cross-links. In the case of low molar mass phenolic substrates, the enzymatic oxidation is reported to lead to polymerization of the phenols. The aim of this work was to investigate if during oxidative cross-linking of proteins oligo-tyrosine cross-links are formed in addition to dityrosine. To this end, alpha-lactalbumin (alpha-LA) was cross linked using horseradish peroxidase (HRP) and hydrogen peroxide (H2O2). The reaction products were acid hydrolysed, after which the cross-linked amino acids were investigated by LC-MS and MALDI-MS. To test the effect of the size of the substrate, the cross-linking reaction was also performed with L-tyrosine, N acetyl L-tyrosinamide and angiotensin. These products were analyzed by LC-MS directly, as well as after acid hydrolysis. In the acid hydrolysates of all samples oligo-tyrosine (Yn, n=3-8) was found in addition to di-tyrosine (Y2). Two stages of cross-linking of alpha-LA were identified: a) 1-2 cross-links were formed per monomer until the monomers were converted into oligomers, and b) subsequent cross-linking of oligomers formed in the first stage to form nanoparticles containing 3-4 cross-links per monomer. The transition from first stage to the second stage coincided with the point where di-tyrosine started to decrease and more oligo-tyrosines were formed. In conclusion, extensive polymerization of alpha-LA using HRP via oligo-tyrosine cross-links is possible, as is the case for low molar mass tyrosine containing substrates. PMID- 26282910 TI - Risk factors for reoperation after initial burr hole trephination in chronic subdural hematomas. AB - BACKGROUND: The optimal management of chronic subdural hematomas remains a challenge. Twist drill craniotomy or burr hole trephination are considered optimal initial treatments, but the reoperation rate for hematoma recurrence and other complications is still high. Therefore, evaluation of possible risk factors for initial treatment failure is crucial. In this context, we performed a study to define a possible subpopulation that may benefit from a more invasive initial treatment regime. METHODS: We retrospectively reviewed the medical charts of 193 patients with 250 chronic subdural hematomas who had undergone burr hole trephination as first-line therapy in our institution between January 2005 and October 2012. To identify risk factors for reoperation, a multivariable logistic regression analysis was performed with reoperation as the dependent variable. Surgical complications, including acute rebleeding, infection and chronic hematoma recurrence, were analyzed separately using a logistic regression model. RESULTS: The mean age of the cohort was 71.4 years. The male/female ratio was 137:56. Reoperation was necessary in 56 cases (29%) for recurrent hematomas and surgical complications. Predictors for reoperation for surgical complications were midline shift (odds ratio [OR] (per mm) 1.16, 95% confidence interval [CI]: 1.05-1.29, p=0.006), arterial hypertension (OR 5.44, 95% CI: 1.45-20.41, p=0.012) and bilateral hematomas (OR 4.22, 95% CI: 1.22-14.58, p=0.023). There was a trend toward a higher risk of surgically-relevant hematoma recurrence in patients with prior treatment with vitamin K antagonists (OR 1.76, 95% CI: 0.75-4.13, p=0.191). CONCLUSION: Burr hole trephination is the therapy of choice in most chronic subdural hematomas, but the rate of recurrent hematomas is high. Every hematoma should be treated individually especially in relation to midline-shift and pre existing conditions. Further prospective studies evaluating types of treatment and hematoma density are needed. PMID- 26282911 TI - Analysis of vestibular schwannoma size: A literature review on consistency with measurement techniques. AB - INTRODUCTION: Vestibular schwannoma (VS) tumor size, a significant prognostic indicator, is closely analyzed in patients undergoing observation or treatment. It has historically been reported in terms of linear size; however, volumetric assessments can now be performed routinely. We examine the use of described measurement techniques in large published clinical series to assess their consistency. METHODS: Computerized searches of the MEDLINE database (Pubmed) from 1975 to August 2014 were conducted with the purpose of identifying large series describing the management of VSs. Articles that reported tumor size measurements were included if they described greater than 600 patients. RESULTS: 19 studies were found fitting the inclusion criteria, consisting of large retrospective studies with sample sizes ranging from 614 to 2991. A total of 17 studies reported linear measurements, while 2 studies reported volumetric assessments of tumor size. Significant variations were found regarding methods for linear measurement. Furthermore, several papers did not provide any details regarding the measurement technique. Inclusion of intracanalicular portions of the tumor was highly variable. Volume assessments were performed by segmented volume analysis. CONCLUSIONS: Among the large published series on VSs, significant variation exists regarding the utilized measurement technique to assess size. Volumetric assessments have the greatest clinical utility, sensitivity and accuracy in measuring tumor size and growth. Standardization of volume assessments will provide the best method for producing consistent literature findings. PMID- 26282912 TI - Association Between Daily Time Spent in Sedentary Behavior and Duration of Hyperglycemia in Type 2 Diabetes. AB - Exercise and sedentary behavior have different physiologic effects, which have yet to be fully explained. Time spent in sedentary behavior has been associated with glucose intolerance in adults at risk for type 2 diabetes, but these data have come largely from cross-sectional studies that have not explored this relationship in adults with diabetes. The specific aim of this study was to examine the relationship between time spent in sedentary behavior and glucose levels in adults diagnosed with type 2 diabetes over 3-5 days. METHODS: Using continuous and concurrent data gathered from wrist accelerometry and a Continuous Glucose-Monitoring Sensor (CGMS), we conducted a longitudinal, descriptive study involving 86 patients with type 2 diabetes. RESULTS: More time spent in sedentary behavior was predictive of significant increases in time spent in hyperglycemia (B = 0.12, p < .05). CONCLUSIONS: These findings highlight the relationship between time spent sedentary and time spent in hyperglycemia, as identified through our use of objective, continuous data collection methods for both sedentary behavior and glucose levels across multiple days (Actiwatch, CGMS). For patients with type 2 diabetes, these findings emphasize the need for the development of individualized interventions aimed at decreasing the amount of time spent in hyperglycemia by reducing sedentary time. PMID- 26282913 TI - Efficacy of transverse abdominis plane block in reduction of postoperation pain in laparoscopic cholecystectomy. AB - OBJECTIVE: Transversus abdominis plane (TAP) block is a recently introduced regional anesthesia technique that is used for postoperative pain reduction in some abdominal surgeries. The present study evaluated the efficacy of the TAP block on the post laparoscopic cholecystectomy pain intensity and analgesic consumption. METHODS: Fifty-four patients were enrolled in three groups: TAP block with normal saline (Group 1, n = 18); TAP block with bupivacaine (Group 2, n = 18); and TAP block with bupivacaine plus sufentanil (Group 3, n = 18). The time to the first fentanyl request, fentanyl consumption in the 24 hours following surgery, and postoperative pain intensity at 30 minutes, 1 hour, 6 hours, 12 hours, and 24 hours following discharge for recovery were measured and recorded. RESULTS: The total amount of 24-hour fentanyl consumption was higher in Group 1 (877.8 +/- 338.8 MUg) than either Group 2 (566.7 +/- 367.8 MUg) or Group 3 (555.5 +/- 356.8 MUg; p = 0.03). Postoperative pain score was higher in Group 1 than intervention groups (p = 0.006); however, there was no significant difference in intervention groups. The time to the first fentanyl request in Group 1 (79.44 +/- 42.2) was significantly lower than Group 3 (206.38 +/- 112.7; p = 0.001). CONCLUSION: The present study demonstrated that bilateral TAP block with 0.5% bupivacaine reduces post laparoscopic cholecystectomy pain intensity and fentanyl request and prolongs time to the first analgesic request. Adding sufentanil to the block solution reduced neither pain intensity nor fentanyl further consumption. PMID- 26282914 TI - Pneumorrhachis as a result of epidural anesthesia. PMID- 26282915 TI - Cardiorespiratory responses to haemolytic anaemia in rainbow trout Oncorhynchus mykiss. AB - To quantify cardiorespiratory response to experimental anaemia in rainbow trout Oncorhynchus mykiss, a 24 h phenylhydrazine treatment was used to reduce haematocrit to almost one third of its initial value over 4-5 days. In response, relative blood velocity in the ventral aorta (an index of cardiac output) progressively increased to more than double to its normocythaemic value and there was no significant change in routine oxygen uptake. Thus, the primary compensatory response to anaemia was an increase in cardiac output. PMID- 26282916 TI - Whole-genome amplification: a useful approach to characterize new genes in unculturable protozoan parasites such as Bonamia exitiosa. AB - Bonamia exitiosa is an intracellular parasite (Haplosporidia) that has been associated with mass mortalities in oyster populations in the Southern hemisphere. This parasite was recently detected in the Northern hemisphere including Europe. Some representatives of the Bonamia genus have not been well categorized yet due to the lack of genomic information. In the present work, we have applied Whole-Genome Amplification (WGA) technique in order to characterize the actin gene in the unculturable protozoan B. exitiosa. This is the first protein coding gene described in this species. Molecular analysis revealed that B. exitiosa actin is more similar to Bonamia ostreae actin gene-1. Actin phylogeny placed the Bonamia sp. infected oysters in the same clade where the herein described B. exitiosa actin resolved, offering novel information about the classification of the genus. Our results showed that WGA methodology is a promising and valuable technique to be applied to unculturable protozoans whose genomic material is limited. PMID- 26282917 TI - Neurological outcomes in symptomatic congenital cytomegalovirus-infected infants after introduction of newborn urine screening and antiviral treatment. AB - BACKGROUND: Newborn screening for urinary cytomegalovirus (CMV) and early introduction of antiviral treatment are expected to improve neurological outcomes in symptomatic congenital CMV-infected infants. This cohort study prospectively evaluated neurological outcomes in symptomatic congenital CMV-infected infants following the introduction of hospital-based newborn urinary CMV screening and antiviral treatment. SUBJECTS/METHODS: Following institutional review board approval and written informed consent from their parents, newborns were prospectively screened from 2009 to 2014 for urinary CMV-DNA by PCR within 1 week after birth at Kobe University Hospital and affiliated hospitals. CMV-positive newborns were further examined at Kobe University Hospital, and those diagnosed as symptomatic were treated with valganciclovir for 6 weeks plus immunoglobulin. Clinical neurological outcomes were evaluated at age ?12 months and categorized by the presence and severity of neurologic sequelae. RESULTS: Urine samples of 6348 newborns were screened, with 32 (0.50%) positive for CMV. Of these, 16 were diagnosed with symptomatic infection and 12 received antiviral treatment. Four infants developed severe impairment (33%), three developed mild impairment (25%), and five developed normally (42%). CONCLUSIONS: This is the first Japanese report of neurological assessments in infants with symptomatic congenital CMV infection who received early diagnosis and antiviral treatment. Urinary screening, resulting in early diagnosis and treatment, may yield better neurological outcomes in symptomatic congenital CMV-infected infants. PMID- 26282918 TI - Surfactant Dependent pH Controlled "off-on", "off-on-off" and "on-off" Fluorescent Switches Exhibited by N-Benzylidenenaphthalen-1-Amine. AB - N-benzylidenenaphthalen-1-amine (L) acts as pH dependent "off-on", "off-on-off" and "on-off" fluorescent switch in 1:1 (v/v) CH3CN:H2O depending on the presence of anionic sodiumdocdecyl sulphate (SDS), neutral triton X-100 (TX-100) and cationic cetyltrimethylammonium bromide (CTAB) surfactants respectively. DFT calculation shows the possibility of formation of L.H(+) due to protonation at immine N and L.OH(-) due to introduction of OH(-) group at immine C. The relative stability of these two cationic and anionic species depends on the charge environment provided by surfactants. This influences the photoinduced electron transfer (PET) processes involved and results in different switch behaviour. PMID- 26282920 TI - A microchip integrating cell array positioning with in situ single-cell impedance measurement. AB - This paper presents a novel microarray chip integrating cell positioning with in situ, real-time and long-time impedance measurement on a single cell. The microchip integrates a plurality of quadrupole-electrode units (termed positioning electrodes) patterned into an array with pairs of planar electrodes (termed measuring electrodes) located at the centers of each quadrupole-electrode unit. The positioning electrodes are utilized to trap and position living cells onto the measuring electrodes based on negative dielectrophoresis (nDEP), while the measuring electrodes are used to measure impedances of the trapped single cells. Each measuring electrode has a small footprint area of 7 * 7 MUm(2) to ensure inhabiting only one single cell on it. However, the electrode with a small surface area has a low double-layer capacitance when it is immersed in a liquid solution, thus generating a large double-layer impedance, which reduces the sensitivity for impedance measurement on the single cell. To enlarge the effective surface areas of the measuring electrodes, a novel surface-modification process is proposed to controllably construct gold nanostructures on the surfaces of the measuring electrodes while the positioning electrodes are unstained. The double layer capacitances of the modified electrodes are increased by about one order after surface-modification. The developed microchip is used to monitor the adhering behavior of a single HeLa cell by measuring its impedance spectra in real time. The measured impedance is analyzed and used to extract cellular electrical parameters, which demonstrated that the cell compresses the electrical double layer in the process of adherence and adheres onto the measuring electrodes after 4-5 hours. PMID- 26282919 TI - AID-expressing epithelium is protected from oncogenic transformation by an NKG2D surveillance pathway. AB - Activation-induced deaminase (AID) initiates secondary antibody diversification in germinal center B cells, giving rise to higher affinity antibodies through somatic hypermutation (SHM) or to isotype-switched antibodies through class switch recombination (CSR). SHM and CSR are triggered by AID-mediated deamination of cytosines in immunoglobulin genes. Importantly, AID activity in B cells is not restricted to Ig loci and can promote mutations and pro-lymphomagenic translocations, establishing a direct oncogenic mechanism for germinal center derived neoplasias. AID is also expressed in response to inflammatory cues in epithelial cells, raising the possibility that AID mutagenic activity might drive carcinoma development. We directly tested this hypothesis by generating conditional knock-in mouse models for AID overexpression in colon and pancreas epithelium. AID overexpression alone was not sufficient to promote epithelial cell neoplasia in these tissues, in spite of displaying mutagenic and genotoxic activity. Instead, we found that heterologous AID expression in pancreas promotes the expression of NKG2D ligands, the recruitment of CD8(+) T cells, and the induction of epithelial cell death. Our results indicate that AID oncogenic potential in epithelial cells can be neutralized by immunosurveillance protective mechanisms. PMID- 26282921 TI - Retraction Note to: Profiling of differentially expressed microRNAs (miRNAs) during differentiation of rat hepatic oval cells (HOCs) into hepatocellular carcinoma (HCC) cells. PMID- 26282923 TI - U.S. Border Enforcement and Mexican Immigrant Location Choice. AB - We provide the first evidence on the causal effect of border enforcement on the full spatial distribution of Mexican immigrants to the United States. We address the endogeneity of border enforcement with an instrumental variables strategy based on administrative delays in budgetary allocations for border security. We find that 1,000 additional Border Patrol officers assigned to prevent unauthorized migrants from entering a U.S. state decreases that state's share of Mexican immigrants by 21.9 %. Our estimates imply that if border enforcement had not changed from 1994 to 2011, the shares of Mexican immigrants locating in California and Texas would each be 8 percentage points greater, with all other states' shares lower or unchanged. PMID- 26282924 TI - Membrane tension and membrane fusion. AB - Diverse cell biological processes that involve shaping and remodeling of cell membranes are regulated by membrane lateral tension. Here we focus on the role of tension in driving membrane fusion. We discuss the physics of membrane tension, forces that can generate the tension in plasma membrane of a cell, and the hypothesis that tension powers expansion of membrane fusion pores in late stages of cell-to-cell and exocytotic fusion. We propose that fusion pore expansion can require unusually large membrane tensions or, alternatively, low line tensions of the pore resulting from accumulation in the pore rim of membrane-bending proteins. Increase of the inter-membrane distance facilitates the reaction. PMID- 26282925 TI - A structural biology perspective on NMDA receptor pharmacology and function. AB - N-methyld-aspartate receptors (NMDARs) belong to the large family of ionotropic glutamate receptors (iGluRs), which are critically involved in basic brain functions as well as multiple neurological diseases and disorders. The NMDARs are large heterotetrameric membrane protein complexes. The extensive extracellular domains recognize neurotransmitter ligands and allosteric compounds and translate the binding information to regulate activity of the transmembrane ion channel. Here, we review recent advances in the structural biology of NMDARs with a focus on pharmacology and function. Structural analysis of the isolated extracellular domains in combination with the intact heterotetrameric NMDAR structure provides important insights into how this sophisticated ligand-gated ion channel may function. PMID- 26282926 TI - Structure, mechanism and cooperation of bacterial multidrug transporters. AB - Cells from all domains of life encode energy-dependent trans-membrane transporters that can expel harmful substances including clinically applied therapeutic agents. As a collective body, these transporters perform as a super system that confers tolerance to an enormous range of harmful compounds and consequently aid survival in hazardous environments. In the Gram-negative bacteria, some of these transporters serve as energy-transducing components of tripartite assemblies that actively efflux drugs and other harmful compounds, as well as deliver virulence agents across the entire cell envelope. We draw together recent structural and functional data to present the current models for the transport mechanisms for the main classes of multi-drug transporters and their higher-order assemblies. PMID- 26282927 TI - Nanolubrication by ionic liquids: molecular dynamics simulations reveal an anomalous effective rheology. AB - This article describes molecular dynamics simulations of an ionic liquid (IL) confined between iron oxide surfaces under relatively high pressure and severe shearing, representative of a typical steel-steel lubricated contact. The simulations reveal the presence of hydrodynamic and thermal slip at the walls, despite the wetting nature of the fluid/wall interface. A crucial consequence of the temperature slip is the subsequent increase of the fluid temperature under shear, which modifies its effective rheology, resulting in saturation of the shear stress at high shear rates. Overall, this article provides a methodology for accurate modeling of tribological contacts lubricated by a nanometer-thick IL film. The results contribute to the debate on the saturation of the shear stress at high shear rates, and reveal the rich phenomenology arising in severe tribological conditions, departing from the traditional understanding of nanofluidic transport, mainly built in the linear response regime and standard thermodynamic conditions. PMID- 26282928 TI - ZapC promotes assembly and stability of FtsZ filaments by binding at a different site on FtsZ than ZipA. AB - ZapC, a component of the divisome in Escherichia coli, is known to co-localize with FtsZ at the mid-cell position. A deletion or an overexpression of ZapC has been found to induce elongation of bacterial cells implying a role of ZapC in the cell division. ZapC has also been shown to enhance the assembly of purified FtsZ. In this study, ZapC was found to prevent the dilution-induced disassembly of preformed FtsZ polymers and to decorate FtsZ protofilaments along the length. ZapC interacted with FtsZ with a dissociation constant of 30+/-7nM. Salt had no discernable effect on the binding of ZapC to FtsZ; however, bis-ANS inhibited the binding of ZapC to FtsZ suggesting that the interaction was predominantly hydrophobic in nature. Several of the positive regulators of FtsZ assembly including ZipA are shown to bind FtsZ at the C-terminal tail of FtsZ. Using a 12 residue C-terminal tail peptide (LDIPAFLRKQAD) of FtsZ and a C-terminal tail truncated FtsZ construct, we provided data suggesting that ZapC does not bind at the C-terminal tail of FtsZ. The results indicated that ZapC and ZipA, two functionally similar proteins of the divisome complex, regulate FtsZ assembly through different sites of action on FtsZ. PMID- 26282929 TI - Metal adsorption by agricultural biosorbents: Adsorption isotherm, kinetic and biosorbents chemical structures. AB - Biosorption of Cu(II), Co(II) and Fe(III) ions from aqueous solutions by rice husk, palm leaf and water hyacinth was investigated as a function of initial pH, initial heavy metal ions concentration and treatment time. The adsorption process was examined by two adsorption isotherms: Langmuir and Freundlich isotherms. The experimental data of biosorption process were analyzed using pseudo-first order, pseudo-second order kinetic models. The equilibrium biosorption isotherms showed that the three studied biosorbents possess high affinity and sorption capacity for Cu(II), Co(II) and Fe(III) ions. Rice husk showed more efficiency than palm leaf and water hyacinth. Adsorption of Cu(II) and Co(II) was more efficient in alkaline medium (pH 9) than neutral medium due to the high solubility of metal ion complexes. The metal removal efficiency of each biosorbent was correlated to its chemical structure. DTA studies showed formation of metal complex between the biosorbents and the metal ions. The obtained results showed that the tested biosorbents are efficient and alternate low-cost biosorbent for removal of heavy metal ions from aqueous media. PMID- 26282930 TI - Electrochemical, spectroscopic, and theoretical studies on the interaction between azathioprine and DNA. AB - Possible interaction between immunosuppressive drug, azathioprine, and calf thymus DNA was explored by cyclic voltammetry, spectrophotometry, competitive spectrofluorimetry, circular dichroism spectroscopy (CD), and viscosity measurements. Cyclic voltammetry showed negative shift in the reduction peak of azathioprine in the presence of DNA, and large decrease in peak current, referring to the predominance of electrostatic forces. The binding constant was calculated to be 1.22*10(3)M(-1). Absorption hyperchromism without shift in wavelength was observed when DNA was added to azathioprine solution. Competitive fluorescence experiments were conducted by using Hoechst 33258 and methylene blue as probes for minor groove and intercalation binding modes, respectively. The studies showed that azathioprine could release Hoechst 33258, while negligible effect was detected in the case of methylene blue. Stern-Volmer quenching constant (KSV) and complex formation constant (Kf) were obtained from the fluorescence measurements to be 7.6*10(3)M(-1) and 7.76*10(4)M(-1), respectively, at 298K. Enthalpy and entropy changes during the interaction between azathioprine and DNA were calculated from Van't Hoff plot (DeltaH=-20.2kJmol(-1); DeltaS=26.11Jmol(-1)K(-1) at 298K) which showed an exothermic spontaneous reaction, and involvement of electrostatic forces in the complex formation with DNA. Moreover, circular dichroism studies revealed that azathioprine induced detectable changes in the negative band of DNA spectrum. Viscosity of DNA solution decreased in the presence of azathioprine, showed a non-intercalative mode of interaction. Finally, molecular docking calculations showed that in the lowest energy level of drug-DNA complex, azathioprine approaches the minor grooves of DNA. PMID- 26282931 TI - Temporal distribution of baseline characteristics and association with early mortality among HIV-positive patients at University College Hospital, Ibadan, Nigeria. AB - The first six months of HIV care and treatment are very important for long-term outcome. Early mortality (within 6 months of care initiation) undermines care and treatment goals. This study assessed the temporal distribution in baseline characteristics and early mortality among HIV patients at the University College Hospital, Ibadan, Nigeria from 2006-2013. Factors associated with early mortality were also investigated. This was a retrospective analysis of data from 14 857 patients enrolled for care and treatment at the adult antiretroviral clinic of the University College Hospital, Ibadan, Nigeria. Effects of factors associated with early mortality were summarised using a hazard ratio with a 95% confidence interval obtained from Cox proportional hazard regression models. The mean age of the subjects was 36.4 (SD=10.2) years with females being in the majority (68.1%). While patients' demographic characteristics remained virtually the same over time, there was significant decline in the prevalence of baseline opportunistic infections (2006-2007=55.2%; 2011-2013=38.0%). Overall, 460 (3.1%) patients were known to have died within 6 months of enrollment in care/treatment. There was no significant trend in incidence of early mortality. Factors associated with early mortality include: male sex, HIV encephalopathy, low CD4 count (< 50 cells), and anaemia. To reduce early mortality, community education should be promoted, timely access to care and treatment should be facilitated and the health system further strengthened to care for high risk patients. PMID- 26282932 TI - The Role of Emergency Medical Services in Geriatrics: Bridging the Gap between Primary and Acute Care. AB - Caring for older adults is a major function of emergency medical services (EMS). Traditional EMS systems were designed to treat single acute conditions; this approach contrasts with best practices for the care of frail older adults. Care might be improved by the early identification of those who are frail and at highest risk for adverse outcomes. Paramedics are well positioned to play an important role via a more thorough evaluation of frailty (or vulnerability). These findings may inform both pre-hospital and subsequent emergency department (ED) based decisions. Innovative programs involving EMS, the ED, and primary care could reduce the workload on EDs while improving patient access to care, and ultimately patient outcomes. Some frail older adults will benefit from the resources and specialized knowledge provided by the ED, while others may be better helped in alternative ways, usually in coordination with primary care. Discerning between these groups is a challenge worthy of further inquiry. In either case, care should be timely, with a focus on identifying emergent or acute care needs, frailty evaluation, mobility assessments, identifying appropriate goals for treatment, promoting functional independence, and striving to have the patient return to their usual place of residence if this can be done safely. Paramedics are uniquely positioned to play a larger role in the care of our aging population. Improving paramedic education as it pertains to geriatrics is a critical next step. PMID- 26282933 TI - Global dimensions of chronic kidney disease of unknown etiology (CKDu): a modern era environmental and/or occupational nephropathy? PMID- 26282934 TI - Selective binding and extraction of aqueous dihydrogen phosphate solutions via three-armed thiourea receptors. AB - A series of neutral anion receptors with one to three thiourea arms were synthesized and their binding to tetrabutylammonium chloride, acetate, and dihydrogen phosphate salts in aqueous DMSO mixtures was examined. The three-armed thiourea host was found to strongly and selectively bind H2PO4(-) even in DMSO solutions containing up to 30% water. This enabled the dihydrogen phosphate salt to be extracted from water into chloroform in its dibasic form despite the high heat of the hydration of HPO4(2-). PMID- 26282936 TI - How to use biologic agents in patients with rheumatoid arthritis who have comorbid disease. AB - Although biologic disease modifying anti-rheumatic drugs (bDMARDs) have improved the quality of life of patients with rheumatoid arthritis, side effects remain a problem, especially for patients with pre-existing comorbidities. Randomized controlled trials of such drugs in rheumatoid arthritis typically exclude patients with comorbidities and are of short duration, so they do not provide data on adverse events in these people. Other data sources such as national bDMARD registries are limited by the preselection of patients for both conventional synthetic chemical compound disease modifying anti-rheumatic drugs (csDMARDs) and bDMARDs, and although these databases document comorbidity, they rarely report its severity. This too limits definitive statements on the progression or resolution of pre-existing disease. Although bDMARDs may not be contraindicated in patients with rheumatoid arthritis and certain comorbid diseases, additional assessments or precautions are recommended. This review summarizes current data on the use of bDMARDs in people with rheumatoid arthritis and common comorbid diseases. It provides an evidence base for doctors and their patients when discussing and selecting the appropriate bDMARDs. PMID- 26282935 TI - Intratumoral interleukin-6 predicts ascites formation in patients with epithelial ovarian cancer: A potential tool for close monitoring. AB - BACKGROUND: The implication of IL-6 in the pathogenesis of epithelial ovarian cancer (EOC) is well documented. Accordingly, the clinicopathological significance of this cytokine in patients' ascites fluid or serum has largely been investigated. Since the main source of IL-6 secreted into the biological fluids is the tumor tissue, this study was designed to investigate the status and possible clinical relevance of the IL-6 expression in an array of EOC tissue specimens. METHODS: Tissue samples obtained from ninety-eight consecutive patients with EOC were studied using immunohistochemistry. Clinicopathological characteristics and treatment related factors were collected from patient files. The relationship between the expression of the protein of interest and the study endpoints of disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. For evaluating the predictive value of IL-6, logistic regression and cox proportional hazards models were employed. RESULTS: An upregulation of IL-6 expression was observed in EOC tissues as compared with the normal samples (p < 0.0001). As regards the clinical relevance, IL-6 failed to predict OS, DFS and response to the platinum-based chemotherapy in EOC patients. In multivariate analysis, however, IL-6 was identified as an independent predictive factor for the development of post-treatment ascites (p:0.033). CONCLUSIONS: Having the capability to predict the ascites formation, IL-6 might serve as a biomarker and a useful tool in EOC for monitoring purposes. IL-6 targeting for the prevention of the ascites development is a potential avenue for further investigation. PMID- 26282937 TI - Operative hysteroscopy versus vacuum aspiration for incomplete spontaneous abortion (HY-PER): study protocol for a randomized controlled trial. AB - BACKGROUND: Incomplete spontaneous abortions are defined by the intrauterine retention of the products of conception after their incomplete or partial expulsion. This condition may be managed by expectant care, medical treatment or surgery. Vacuum aspiration is currently the standard surgical treatment in most centers. However, operative hysteroscopy has the advantage over vacuum aspiration of allowing the direct visualization of the retained conception product, facilitating its elective removal while limiting surgical complications. Inadequately powered retrospective studies reported subsequent fertility to be higher in patients treated by operative hysteroscopy than in those treated by vacuum aspiration. These data require confirmation in a randomized controlled trial comparing fertility rates between women undergoing hysteroscopy and those undergoing vacuum aspiration for incomplete spontaneous abortion. METHODS: After providing written informed consent, 572 women with incomplete spontaneous abortion recruited from 15 centers across France will undergo randomization by a centralized computer system for treatment by either vacuum aspiration or operative hysteroscopy. Patients will not be informed of the type of treatment that they receive and will be cared for during their hospital stay in accordance with standard practices at each center. The patients will be monitored for pregnancy or adverse effects by a telephone conversation or questionnaire sent by e-mail or post over a period of two years. In cases of complications, failure of the intervention or diagnosis of uterine cavity disease, patient care will be left to the discretion of the medical center team. DISCUSSION: If our hypothesis is confirmed, this study will provide evidence that the use of operative hysteroscopy can increase the number of pregnancies continuing beyond 22 weeks of gestation in the two-year period following incomplete spontaneous abortion without increasing the incidence of morbidity and peri- and postoperative complications. The standard surgical treatment of this condition would thus be modified. This study would therefore have a large effect on the surgical management of incomplete spontaneous abortion. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02201732 ; registered on 17 July 2014. PMID- 26282938 TI - Anti-inflammatory effects of interleukin-35 in acquired aplastic anemia. AB - Interleukin (IL)-35 is a novel regulatory cytokine primarily produced by regulatory T cells. Accumulating evidence has established that IL-35 plays an important role in the regulation of immune homeostasis, but little is known regarding the function of IL-35 in acquired aplastic anemia (AA). The aim of the present study was to investigate the expression of IL-35 and its effects on T cell response in AA. Our study demonstrated that significantly decreased plasma levels of IL-35 in AA were closely correlated with disease severity. In vitro stimulation experiment further confirmed the anti-inflammatory effects of IL-35, including suppressing the proliferation of CD4(+) and CD8(+) effector T cells, inhibiting the secretion of interferon-gamma, tumor necrosis factor-alpha and IL 17 and promoting the production of transforming growth factor-beta by peripheral blood mononuclear cells from patients with AA. Furthermore, we established that IL-35 inhibited the differentiation of type 1 T cells and T helper 17 cells but promoted the differentiation of type 2 T cells. Accordingly, the expression of T bet and RORgammat was inhibited while the expression of GATA3 was induced after IL-35 treatment. In summary, our findings suggested that decreased IL-35 might contribute to the loss of immune-tolerance and be critically involved in the pathogenesis of AA. PMID- 26282940 TI - Recent Progress in Chemical Modifications of Chlorophylls and Bacteriochlorophylls for the Applications in Photodynamic Therapy. AB - Since photodynamic therapy emerged as a promising cancer treatment, the development of photosensitizers has gained great interest. In this context, the photosynthetic pigments, chlorophylls and bacteriochlorophylls, as excellent natural photosensitizers, attracted much attention. In effect, several (bacterio) chlorophyll-based phototherapeutic agents have been developed and (or are about to) enter the clinics. The aim of this review article is to give a survey of the advances in the synthetic chemistry of these pigments which have been made over the last decade, and which are pertinent to the application of their derivatives as photosensitizers for photodynamic therapy (PDT). The review focuses on the synthetic strategies undertaken to obtain novel derivatives of (bacterio)chlorophylls with both enhanced photosensitizing and tumorlocalizing properties, and also improved photo- and chemical stability. These include modifications of the C- 17-ester moiety, the isocyclic ring, the central binding pocket, and the derivatization of peripheral functionalities at the C-3 and C-7 positions with carbohydrate-, peptide-, and nanoparticle moieties or other residues. The effects of these modifications on essential features of the pigments are discussed, such as the efficiency of reactive oxygen species generation, photostability, phototoxicity and interactions with living organisms. The review is divided into several sections. In the first part, the principles of PDT and photosensitizer action are briefly described. Then the relevant photophysical features of (bacterio)chlorophylls and earlier approaches to their modification are summarized. Next, a more detailed overview of the progress in synthetic methods is given, followed by a discussion of the effects of these modifications on the photophysics of the pigments and on their biological activity. PMID- 26282941 TI - Current Advances in Antitubercular Drug Discovery: Potent Prototypes and New Targets. AB - Tuberculosis (TB) is an infectious disease caused by bacterium of the Mycobacterium genus, mainly by Mycobacterium tuberculosis (MTB). The World Health Organization aims to substantially reduce the number of cases in the coming years; however, the increased number of multidrug-resistant (MDR) and extremely drug-resistant (XDR) forms of the bacterium and the lack of treatment for latent tuberculosis are challenges to be overcome. In this review, we have identified the most potent compounds described in the literature during recent years with MIC values < 7 uM, low toxicity and a high selective index. In addition, emerging targets in MTB are presented to provide new perspectives for the discovery of new antitubercular drugs. This review aims to summarize the current advances in and promote insights into antitubercular drug discovery. PMID- 26282942 TI - Flexibility as a Strategy in Nucleoside Antiviral Drug Design. AB - As far back as Melville Wolfrom's acyclic sugar synthesis in the 1960's, synthesis of flexible nucleoside analogues have been an area of interest. This concept, however, went against years of enzyme-substrate binding theory. Hence, acyclic methodology in antiviral drug design did not take off until the discovery and subsequent FDA approval of such analogues as Acyclovir and Tenofovir. More recently, the observation that flexible nucleosides could overcome drug resistance spawned a renewed interest in the field of nucleoside drug design. The next generation of flexible nucleosides shifted the focus from the sugar moiety to the nucleobase. With analogues such as Seley-Radtke "fleximers", and Herdewijn's C5 substituted 2'-deoxyuridines, the area of base flexibility has seen great expansion. More recently, the marriage of these methodologies with acyclic sugars has resulted in a series of acyclic flex-base nucleosides with a wide range of antiviral properties, including some of the first to exhibit anti coronavirus activity. Various flexible nucleosides and their corresponding nucleobases will be compared in this review. PMID- 26282939 TI - Unfolded Protein Response and PERK Kinase as a New Therapeutic Target in the Pathogenesis of Alzheimer's Disease. AB - Recent evidence suggests that the development of Alzheimer's disease (AD) and related cognitive loss is due to mutations in the Amyloid Precursor Protein (APP) gene on chromosome 21 and increased activation of eukaryotic translation initiation factor-2alpha (eIF2alpha) phosphorylation. The high level of misfolded and unfolded proteins loading in Endoplasmic Reticulum (ER) lumen triggers ER stress and as a result Unfolded Protein Response (UPR) pathways are activated. Stress-dependent activation of the protein kinase RNA-like endoplasmic reticulum kinase (PERK) leads to the significant elevation of phospho-eIF2alpha. That attenuates general translation and, on the other hand, promotes the preferential synthesis of Activating Transcription Factor 4 (ATF4) and secretase beta (BACE1) a pivotal enzyme responsible for the initiation of the amyloidogenic pathway resulting in the generation of the amyloid beta (Abeta) variant with high ability to form toxic senile plaques in AD brains. Moreover, excessive, long-term stress conditions may contribute to inducing neuronal death by apoptosis as a result of the overactivated expression of pro-apoptotic proteins via ATF4. These findings allow to infer that dysregulated translation, increased expression of BACE1 and ATF4, as a result of eIF2alpha phosphorylation, may be a major contributor to structural and functional neuronal loss resulting in memory impairment. Thus, blocking PERK-dependent eIF2alpha phosphorylation through specific, small molecule PERK branch inhibitors seems to be a potential treatment strategy for AD individuals. That may contribute to the restoration of global translation rates and reduction of expression of ATF4 and BACE1. Hence, the treatment strategy can block accelerated beta -amyloidogenesis by reduction in APP cleaving via the BACE1-dependent amyloidogenic pathway. PMID- 26282943 TI - Antibacterial Nucleoside Natural Products Inhibiting Phospho-MurNAc-Pentapeptide Translocase; Chemistry and Structure-Activity Relationship. AB - The continued emergence of drug-resistance to existing antibacterial agents represents a severe and ongoing public health concern, which demands the discovery of new antibiotics. However the number of novel classes of antibacterial drugs launched in the clinic has been remarkably slow since the 1960s, and it is urgent to develop novel antibacterial agents to fight against drug-resistant bacterial pathogens. Peptidoglycan is a component of the bacterial cell wall, which consists of a repeated N-acetylmuramic acid (MurNAc) and Nacetylglucosamine (GluNAc) polymer cross-linked with polypeptides, and is a good target for antibacterial drug discovery. Among enzymes responsible for its biosynthesis, phospho-MurNAc-pentapeptide translocase (MraY) is a novel and promising target. Many nucleoside natural products, which strongly inhibit MraY, have been found in nature. This review will summarize the synthesis and biological properties of selected MraY inhibitory nucleoside natural products and their analogues synthesized in our laboratory and by others. PMID- 26282945 TI - Expression of NLRP3 in subcutaneous adipose tissue is associated with coronary atherosclerosis. AB - OBJECTIVES: The promotion of adipose tissue inflammation by lifestyle-related diseases such as obesity and diabetes accelerates atherogenesis; however, the underlying mechanisms remain incompletely understood. Nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome contributes to chronic inflammation in adipose tissue. Here, we investigated the link between NLRP3 expression in subcutaneous adipose tissue (SAT) and the severity of coronary atherosclerosis. METHODS AND RESULTS: SAT was obtained from 72 patients who underwent heart device implantation and coronary angiography. Expression of NLRP3 inflammasome-related molecules (NLRP3, IL-1beta and IL-18) in SAT were evaluated by quantitative RT-PCR. Laboratory markers related to lifestyle-related diseases were measured. Patients with obesity, dyslipidemia (P < 0.05, respectively), diabetes or hyperuricemia (P < 0.01, respectively) had significantly higher expression of NLRP3. Multivariate analysis demonstrated that body mass index and serum level of uric acid were predictors of NLRP3 expression in SAT. The expression of NLRP3 in SAT correlated negatively with serum adiponectin level (r = -0.23, P < 0.05). Patients with coronary artery disease showed higher NLRP3 expression than patients without significant stenosis (P < 0.01). Furthermore, the expression of NLRP3 in SAT correlated positively with the severity of coronary atherosclerosis as determined by Gensini score (r = 0.47, P < 0.0001) or SYNTAX score (r = 0.55, P < 0.0001). Multiple regression analysis revealed that the expression of NLRP3 in SAT remains as an independent predictors for the severity of coronary atherosclerosis. CONCLUSIONS: The expression of NLRP3 in SAT, which is affected by lifestyle-related diseases, is associated with the severity of coronary atherosclerosis. Our results suggest that NLRP3 inflammasome in SAT may have a role in atherogenesis. PMID- 26282946 TI - Cascade screening of familial hypercholesterolemia must go on. AB - PURPOSE: This study assesses the success of the recently terminated Dutch nationwide cascade screening by examining whether children with familial hypercholesterolemia (FH) were identified through family screening or due to cardiovascular (CVD) events in the FH parent. METHODS: We collected clinical information of all children (0-18 years) with FH with a pathogenic variant at our outpatient lipid clinic between 1992 and 2014 and their FH parents and FH grandparents. RESULTS: We analysed 292 FH children from 205 parents with FH. A history of premature CVD was present in 20% of the parents (29% of the fathers, 9% of the mothers) and 49% of the FH grandparents. CONCLUSION: The fact that CVD is still a presenting event of FH in especially fathers shows that nationwide screening might have been terminated too early. Therefore we recommend to proceed the cascade screening. PMID- 26282944 TI - Adherence and future discontinuation of tyrosine kinase inhibitors in chronic phase chronic myeloid leukemia. A patient-based survey on 1133 patients. AB - Therapeutic approach for chronic myeloid leukemia (CML) patients has undergone a revolutionary change with the introduction of tyrosine kinase inhibitors, which improved overall survival and quality of life. Optimal therapy adherence has become of paramount importance to maximize the benefits in the long-term outcome. Several evidences have been reported that personal factors, such as social support, psychological and subjective perceptions about the drug used and the future, could influence adherence. We here report the results of a questionnaire specifically designed to evaluate factors influencing adherence and perceptions about the future, distributed to patients during regional Italian meetings. Overall, 1133 patients compiled the questionnaire: median age was 57 years. High rate of adherence was reported, but 42% of interviewed patients admitted that they had occasionally postponed a dose and 58% had discontinued therapy mainly for forgetfulness. The majority of patients discussed with personal physician about the importance of adherence and received sufficient information about illness and treatment, but would like to have discussed more about discomfort, anxiety and fear of the future. Summarizing personal drug compliance and estimating how many days a month, on average, the patients did not take the drug, the majority answered that it was less than 3 days (55%) and only a minority (4%) admitted that it was more than 7 days. Interviewed about discontinuation, 49% of patients answered that wouldn't interrupt because of fear of losing all the results achieved so far. This study suggests a higher level of satisfaction with more information received but the need of improving communication about possible future treatment free remission. PMID- 26282948 TI - Erratum to: 'Antitumor and antimetastatic activities of chloroform extract of medicinal mushroom Cordyceps taii in mouse models'. PMID- 26282947 TI - Periodontal microbiota and phospholipases: the Oral Infections and Vascular Disease Epidemiology Study (INVEST). AB - OBJECTIVE: Periodontal infections have been linked to cardiovascular disease, including atherosclerosis, and systemic inflammation has been proposed as a possible mediator. Secretory phospholipase A2 (s-PLA2) and Lipoprotein-associated PLA2 (Lp-PLA2) are inflammatory enzymes associated with atherosclerosis. No data are available on the association between oral microbiota and PLA2s. We studied whether a relationship exists between periodontal microbiota and the activities of these enzymes. METHODS: The Oral Infection and Vascular Disease Epidemiology Study (INVEST) collected subgingival biofilms and serum samples from 593 dentate men and women (age 68.7 +/- 8.6 years). 4561 biofilm samples were collected in the two most posterior teeth of each quadrant (average 7/participant) for quantitative assessment of 11 bacterial species using DNA-DNA checkerboard hybridization. Mean concentration of s-PLA2 and activities of s-PLA2 and Lp-PLA2 were regressed on tertiles of etiologic dominance (ED). ED is defined as the level of presumed periodontopathic species/combined level of all eleven species measured, and represents the relative abundance of periodontopathic organisms. Analyses were adjusted for age, sex, race/ethnicity, education, smoking, BMI, diabetes, LDL cholesterol and HDL cholesterol, and systolic blood pressure. RESULTS: Higher levels of s-PLA2 activity were observed across increasing tertiles of etiologic dominance (0.66 +/- 0.04 nmol ml(-1) min(-1), 0.73 +/- 0.04 nmol ml(-1) min(-1), 0.89 +/- 0.04 nmol ml-1 min-1; p < 0.001), with also a trend of association between Lp-PLA2 activity and ED (p = 0.07), while s-PLA2 concentration was unrelated to ED. CONCLUSION: Increasingly greater s-PLA2 activity at higher tertiles of etiologic dominance may provide a mechanistic explanatory link of the relationship between periodontal microbiota and vascular diseases. Additional studies investigating the role of s-PLA2 are needed. PMID- 26282949 TI - ASGE position statement on endoscopic bariatric therapies in clinical practice. PMID- 26282950 TI - Multilocus phylogeography of the common midwife toad, Alytes obstetricans (Anura, Alytidae): Contrasting patterns of lineage diversification and genetic structure in the Iberian refugium. AB - Recent investigations on the evolutionary history of the common midwife toad (Alytes obstetricans) revealed high levels of geographically structured genetic diversity but also a situation where delineation of major historical lineages and resolution of their relationships are much more complex than previously thought. We studied sequence variation in one mitochondrial and four nuclear genes throughout the entire distribution range of all recognized A. obstetricans subspecies to infer the evolutionary processes that shaped current patterns of genetic diversity and population subdivision. We found six divergent, geographically structured mtDNA haplogroups diagnosing population lineages, and varying levels of admixture in nuclear markers. Given the timeframe inferred for the splits between major lineages, the climatic and environmental changes that occurred during the Pleistocene seem to have shaped the diversification history of A. obstetricans. Survival of populations in allopatric refugia through the Ice Ages supports the generality of the "refugia-within-refugia" scenario for the Iberian Peninsula. However, lineages corresponding to subspecies A. o. almogavarii, A. o. pertinax, A. o. obstetricans, and A. o. boscai responded differently to Pleistocene climatic oscillations after diverging from a common ancestor. Alytes o. obstetricans expanded northward from a northern Iberian refugium through the western Pyrenees, leaving a signal of contrasting patterns of genetic diversity, with a single mtDNA haplotype north of the Pyrenees from SW France to Germany. Both A. o. pertinax and A. o. boscai are widespread and genetically diverse in Iberia, the latter comprising two divergent lineages with a long independent history. Finally, A. o. almogavarii is mostly restricted to the north-eastern corner of Iberia north of the Ebro river, with additional populations in a small region in south-eastern France. This taxon exhibits unparalleled levels of genetic diversity and little haplotype sharing with other lineages, suggesting a process of incipient speciation. PMID- 26282951 TI - Chemotherapeutic effect of a novel temozolomide analog on nasopharyngeal carcinoma in vitro and in vivo. AB - BACKGROUND: Many patients with nasopharyngeal carcinoma (NPC) face poor prognosis. Due to its hidden anatomical location, the tumor is usually diagnosed quite late, and despite initially successful treatment with radiation and cisplatin, many patients will relapse and succumb to the disease. New treatment options are urgently needed. We have performed preclinical studies to evaluate the potential NPC therapeutic activity of a newly developed analog of temozolomide (TMZ), an alkylating agent that is the current chemotherapeutic standard of care for patients with malignant glioma. RESULTS: TMZ was covalently conjugated to the natural monoterpene perillyl alcohol (POH), creating the novel fusion compound NEO212. Its impact on two NPC cell lines was studied through colony formation assays, cell death ELISA, immunoblots, and in vivo testing in tumor-bearing mice. In vitro, NEO212 effectively triggered tumor cell death, and its potency was significantly greater than that of its individual components, TMZ or POH alone. Intriguingly, merely mixing TMZ with POH also was unable to achieve the superior potency of the conjugated compound NEO212. Treatment of NPC cells with NEO212 inactivated the chemoprotective DNA repair protein MGMT (O6 methylguanine methyltransferase), resulting in significant chemosensitization of cells to a second round of drug treatment. When tested in vivo, NEO212 reduced tumor growth in treated animals. CONCLUSION: Our results demonstrate anticancer activity of NEO212 in preclinical NPC models, suggesting that this novel compound should be evaluated further for the treatment of patients with NPC. PMID- 26282953 TI - Assessing the Accuracy of Three National Physician Sampling Frames. PMID- 26282952 TI - The Roles of Cost and Quality Information in Medicare Advantage Plan Enrollment Decisions: an Observational Study. AB - BACKGROUND: To facilitate informed decision-making in the Medicare Advantage marketplace, the Centers for Medicare & Medicaid Services publishes plan information on the Medicare Plan Finder website, including costs, benefits, and star ratings reflecting quality. Little is known about how beneficiaries weigh costs versus quality in enrollment decisions. OBJECTIVE: We aimed to assess associations between publicly reported Medicare Advantage plan attributes (i.e., costs, quality, and benefits) and brand market share and beneficiaries' enrollment decisions. DESIGN, SETTING, PARTICIPANTS: We performed a nationwide, beneficiary-level cross-sectional analysis of 847,069 beneficiaries enrolling in Medicare Advantage for the first time in 2011. MAIN MEASURES: Matching beneficiaries with their plan choice sets, we used conditional logistic regression to estimate associations between plan attributes and enrollment to assess the proportion of enrollment variation explained by plan attributes and willingness to pay for quality. KEY RESULTS: Relative to the total variation explained by the model, the variation in plan choice explained by premiums (25.7 %) and out-of-pocket costs (11.6 %) together explained nearly three times as much as quality ratings (13.6 %), but brand market share explained the most variation (35.3 %). Further, while beneficiaries were willing to pay more in total annual combined premiums and out-of-pocket costs for higher-rated plans (from $4,154.93 for 2.5-star plans to $5,698.66 for 5-star plans), increases in willingness to pay diminished at higher ratings, from $549.27 (95 %CI: $541.10, $557.44) for a rating increase from 2.5 to 3 stars to $68.22 (95 %CI: $61.44, $75.01) for an increase from 4.5 to 5 stars. Willingness to pay varied among subgroups: beneficiaries aged 64-65 years were more willing to pay for higher-rated plans, while black and rural beneficiaries were less willing to pay for higher-rated plans. CONCLUSIONS: While beneficiaries prefer higher-quality and lower-cost Medicare Advantage plans, marginal utility for quality diminishes at higher star ratings, and their decisions are strongly associated with plans' brand market share. PMID- 26282955 TI - Evaluation of genotoxicity using automated detection of gammaH2AX in metabolically competent HepaRG cells. AB - The in situ detection of gammaH2AX was recently reported to be a promising biomarker of genotoxicity. In addition, the human HepaRG hepatoma cells appear to be relevant for investigating hepatic genotoxicity since they express most of drug metabolizing enzymes and a wild type p53. The aim of this study was to determine whether the automated in situ detection of gammaH2AX positive HepaRG cells could be relevant for evaluation of genotoxicity after single or long-term repeated in vitro exposure compared to micronucleus assay. Metabolically competent HepaRG cells were treated daily with environmental contaminants and genotoxicity was evaluated after 1, 7 and 14 days. Using these cells, we confirmed the genotoxicity of aflatoxin B1 and benzo(a)pyrene and demonstrated that dimethylbenzanthracene, fipronil and endosulfan previously found genotoxic with comet or micronucleus assays also induced gammaH2AX phosphorylation. Furthermore, we showed that fluoranthene and bisphenol A induced gammaH2AX while no effect had been previously reported in HepG2 cells. In addition, induction of gammaH2AX was observed with some compounds only after 7 days, highlighting the importance of studying long-term effects of low doses of contaminants. Together, our data demonstrate that automated gammaH2AX detection in metabolically competent HepaRG cells is a suitable high-through put genotoxicity screening assay. PMID- 26282956 TI - Specialized stroke rehabilitation services in seven countries: Preliminary results from nine rehabilitation centers. AB - BACKGROUND: There is a lack of defined levels of rehabilitation, indicating possibly random content and access to specialized services. AIMS AND/OR HYPOTHESIS: The aim of the study was to perform a multinational descriptive study of specialized rehabilitation in persons with stroke, to elucidate what the different centers define as prerequisites for specialized rehabilitation, and to analyze whether these descriptions map to currently applied standards or constructs of specialized rehabilitation. A secondary aim was to look for similarities and differences between therapies and services for persons with stroke in the sub-acute stage in the different institutions. METHODS: Descriptive data of the collaborating centers regarding structure and processes of services were recorded and compared with the British Society of Rehabilitation Medicine and Specialized Services National Definitions sets. RESULTS: Comparisons of the definitions showed that all centers admitted severely disabled persons with stroke, in need of complex rehabilitation, and provided high levels of physical services, with specialized equipment and facilities. However, funding, size, university affiliation, quality accreditation, staffing levels, specialist training, cognitive and vocational services, coordination of the professional teams, admission procedures, time and type of therapies, estimated length of stay, and follow-up procedures differed between the centers. CONCLUSION: This multinational study of specialized stroke rehabilitation centers shows that a universal definition of specialized rehabilitation is possible, even in quite different countries and settings, in terms of general principles. There were however differences in structures and procedures, which may influence patients' outcomes, indicating a need for refinement of the definitions to be globally applicable. PMID- 26282954 TI - Medication Adherence Does Not Explain Black-White Differences in Cardiometabolic Risk Factor Control among Insured Patients with Diabetes. AB - BACKGROUND: Among patients with diabetes, racial differences in cardiometabolic risk factor control are common. The extent to which differences in medication adherence contribute to such disparities is not known. We examined whether medication adherence, controlling for treatment intensification, could explain differences in risk factor control between black and white patients with diabetes. METHODS: We identified three cohorts of black and white patients treated with oral medications and who had poor risk factor control at baseline (2009): those with glycated hemoglobin (HbA1c) >8 % (n = 37,873), low-density lipoprotein cholesterol (LDL-C) >100 mg/dl (n = 27,954), and systolic blood pressure (SBP) >130 mm Hg (n = 63,641). Subjects included insured adults with diabetes who were receiving care in one of nine U.S. integrated health systems comprising the SUrveillance, PREvention, and ManagEment of Diabetes Mellitus (SUPREME-DM) consortium. Baseline and follow-up risk factor control, sociodemographic, and clinical characteristics were obtained from electronic health records. Pharmacy-dispensing data were used to estimate medication adherence (i.e., medication refill adherence [MRA]) and treatment intensification (i.e., dose increase or addition of new medication class) between baseline and follow-up. County-level income and educational attainment were estimated via geocoding. Logistic regression models were used to test the association between race and follow-up risk factor control. Models were specified with and without medication adherence to evaluate its role as a mediator. RESULTS: We observed poorer medication adherence among black patients than white patients (p < 0.01): 50.6 % of blacks versus 39.7 % of whites were not highly adherent (i.e., MRA <80 %) to HbA1c oral medication(s); 58.4 % of blacks and 46.7 % of whites were not highly adherent to lipid medication(s); and 33.4 % of blacks and 23.7 % of whites were not highly adherent to BP medication(s). Across all cardiometabolic risk factors, blacks were significantly less likely to achieve control (p < 0.01): 41.5 % of blacks and 45.8 % of whites achieved HbA1c <8 %; 52.6 % of blacks and 60.8 % of whites achieved LDL-C <100; and 45.7 % of blacks and 53.6 % of whites achieved SBP <130. Adjusting for medication adherence/treatment intensification did not alter these patterns or model fit statistics. CONCLUSIONS: Medication adherence failed to explain observed racial differences in the achievement of HbA1c, LDL-C, and SBP control among insured patients with diabetes. PMID- 26282961 TI - Robotic total endoscopic sutureless aortic valve replacement: proof of concept for a future surgical setting. AB - BACKGROUND: Sutureless valves have recently enabled closed chest aortic valve replacement. This paper evaluates the feasibility of a robotic telemanipulation during thoracoscopic sutureless aortic valve implantation in cadavers. METHODS: Cadavers were prepared with a five thoracosopic trocar setting, with a transthoracic clamp inserted in the first right intercostal space and the optics inserted in the second. Seven sutureless valve implantations were scheduled using 5 Sorin Perceval and 2 Medtronic 3f Enable valves. RESULTS: In all cases performance of pericardial suspension, aortotomy and root exposure required less than 20 min. Native valve excision and sutureless bioprosthesis implantation was technically feasible in all cases. A satisfactory prosthesis sealing was ascertained visually and the absence of paravalvular leakages was assessed with a nerve hook test around the prosthetic flange. CONCLUSIONS: Closed chest and robot assisted sutureless valve implantation is feasible in cadavers. Robotic technology can enhance reproducibility of the technique. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26282962 TI - Surface-Enhanced Infrared Spectroscopic Study of a CO-Covered Pt Electrode in Room-Temperature Ionic Liquid. AB - ATR-SEIRAS is extended for the first time to study potential-induced surface and interface structure variation of a CO-covered Pt electrode in a room-temperature ionic liquid of N-butyl-N-methyl-piperidinium bis((trifluoromethyl)sulfonyl)imide (or [Pip14][TNf2]). Owing to a wide effective potential window of [Pip14][TNf2], a gradual conversion from bridged COad (COB) to terminal COad (COL) is observed in response to positively going potentials, suggesting that [Pip14](+) may be involved in a strong electrostatic interaction with the COad. This site conversion enables the ratio of the apparent absorption coefficient of COL to that of COB to be determined. Also, the spectral results reveal the potential dependent COad frequency variations as well as the potential-induced interfacial ionic reorientation and movement at the Pt/CO/[Pip14][TNf2] interface. PMID- 26282963 TI - Measurement of an Electronic Resonance in a Ground-State, Gas-Phase Acetophenone Cation via Strong-Field Mass Spectrometry. AB - A one-photon ionic resonance is measured in the strong-field regime in acetophenone by recording the mass spectra as a function of excitation wavelength from 800 to 1500 nm. The ratio of the benzoyl to parent ion signals in the mass spectrum varies significantly with excitation wavelength, where the highest ratio observed upon excitation at 1370 nm (0.90 eV) indicates the presence of a one photon resonance. At the resonant wavelength, the ratio of the benzoyl to parent ion signals increases linearly with laser intensity over a range from 1.1 * 10(13) to 6.0 * 10(13) W cm(-2). The ratio increases by a factor of 5 at 1370 nm with increasing pulse duration from 60 to 100 fs. Calculations using the equation of motion coupled cluster method support the existence of a one-photon transition from the ground ionic to a dissociative excited ionic state (0.87 eV), where motion of the acetyl group from a planar to nonplanar structure within the pulse duration enables the otherwise forbidden transition. PMID- 26282964 TI - Atom-Scale Reaction Pathways and Free-Energy Landscapes in Oxygen Plasma Etching of Graphene. AB - We report first-principles molecular dynamics calculations combined with rare events sampling techniques that clarify atom-scale mechanisms of oxygen plasma etching of graphene. The obtained reaction pathways and associated free-energy landscapes show that the etching proceeds near vacancies via a two-step mechanism, formation of precursor lactone structures and the subsequent exclusive CO2 desorption. We find that atomic oxygen among the plasma components is most efficient for etching, providing a guidline in tuning the plasma conditions. PMID- 26282965 TI - Stimulated Emission Properties of Sterically Modified Distyrylbenzene-Based H Aggregate Single Crystals. AB - J-aggregation has been shown to be beneficial for light amplification in single crystals of pi-conjugated organic molecules. In the case of H-aggregation, the criteria for such processes are still under debate. It has also been shown that H aggregate arrangements with considerable pi-pi overlap are detrimental for light amplification. We show here that a proper alignment of the molecules in the crystal lattice, which minimizes pi-pi overlap between adjacent molecules, gives rise to (random) stimulated emission from cofacial arrangements similar to that of the herringbone aggregates. PMID- 26282966 TI - Drug-Drug Interactions within Protein Cavities Probed by Triplet-Triplet Energy Transfer. AB - A new direct and noninvasive methodology based on transient absorption spectroscopy has been developed to probe the feasibility of drug-drug interactions within a common protein binding site. The simultaneous presence of (R)-cinacalcet (CIN) and (S)-propranolol (PPN) within human or bovine alpha1-acid glycoproteins (AAGs) is revealed by detection of (3)CIN* as the only transient species after laser flash photolysis of CIN/PPN/AAG mixtures at 308 nm. This is the result of triplet-triplet energy transfer from (3)PPN* to CIN, which requires close contact between the two drugs within the same biological compartment. Similar results are obtained with nabumetone and CIN as donor/acceptor partners. This new methodology can, in principle, be extended to a variety of drug/drug/biomolecule combinations. PMID- 26282967 TI - Cage-Like Local Structure of Ionic Liquids Revealed by a (129)Xe Chemical Shift. AB - The chemical shift of xenon (at natural abundance) dissolved in a variety of 1 butyl-3-methylimidazolium-based ionic liquids (ILs) has been measured with (129)Xe NMR spectroscopy. The large chemical shift differences observed are mainly related to the type of anion; the strongest deshielding effect is observed ILs with I(-), Br(-), and Cl(-) anions, and the strongest shielding is found for the bis(trifluoromethanesulfonyl)imide ([Tf2N](-))-based IL. The measured (129)Xe chemical shift variations correlate well with the IL structure organization imposed by the anions and with the size of the empty voids due to charge alternation patterns. Descriptors taken from literature data on X-ray and neutron scattering, as well as single-crystal structures where available, support this interpretation. The proposed methodology adds a new investigating tool to the elucidation of the short-range order in ILs. The observed chemical shift trend provides information about how these solvents are organized. PMID- 26282968 TI - Efficient Computational Screening of Organic Polymer Photovoltaics. AB - There has been increasing interest in rational, computationally driven design methods for materials, including organic photovoltaics (OPVs). Our approach focuses on a screening "pipeline", using a genetic algorithm for first stage screening and multiple filtering stages for further refinement. An important step forward is to expand our diversity of candidate compounds, including both synthetic and property-based measures of diversity. For example, top monomer pairs from our screening are all donor-donor (D-D) combinations, in contrast with the typical donor-acceptor (D-A) motif used in organic photovoltaics. We also find a strong "sequence effect", in which the average HOMO-LUMO gap of tetramers changes by ~0.2 eV as a function of monomer sequence (e.g., ABBA versus BAAB); this has rarely been explored in conjugated polymers. Beyond such optoelectronic optimization, we discuss other properties needed for high-efficiency organic solar cells, and applications of screening methods to other areas, including non fullerene n-type materials, tandem cells, and improving charge and exciton transport. PMID- 26282969 TI - Metal Oxide Photoelectrodes for Solar Fuel Production, Surface Traps, and Catalysis. AB - The photoelectrochemical reduction of water or CO2 is a promising route to sustainable solar fuels but hinges on the identification of a stable photoanode for water oxidation. Semiconductor oxides like Fe2O3 and BiVO4 have been gaining significant attention as promising materials. However, they exhibit a major drawback of a large required overpotential for solar water oxidation. In this Perspective, recent efforts to characterize and reduce the overpotential are critically examined. The accumulation of photogenerated holes at the semiconductor-liquid interface, recently observed with multiple techniques, is rationalized with surface state models. Transient absorption spectroscopy and electrochemical impedance spectroscopy suggest that surface treatments designed to either passivate surface traps or increase reaction rates (as catalysts) actually perform identically. This calls into question the definition of a catalyst when coupled to a semiconductor photoelectrode. In contrast, results from transient photocurrent spectroscopy suggest that two separate loss mechanisms are indeed occurring and can be addressed separately. PMID- 26282970 TI - Excitation Nature of Two-Photon Photoluminescence of Gold Nanorods and Coupled Gold Nanoparticles Studied by Two-Pulse Emission Modulation Spectroscopy. AB - Gold nanorods (Au NRs) and coupled gold nanospheres (Au NSs) are known to display strong two-photon photoluminescence (TPPL). Here two-pulse emission modulation (TPEM) and pump-probe measurements were performed on Au NRs and coupled Au NSs to understand their excitation mechanisms. The TPEM cross contributions of Au NRs and coupled Au NSs showed much slower decay compared with a two-photon absorption organic dye. Their decay time constants (4.0 ps for Au NRs and 3.1 ps for coupled Au NSs) match well with the lifetimes of intermediate states measured from pump probe experiments. These results support the fact that strong TPPL in Au NRs and coupled Au NSs arises from two sequential one-photon absorption steps involving real intermediate states instead of coherent two-photon absorption. These results give direct evidence that previously observed aggregation-enhanced TPPL arises from enhanced two-photon excitation efficiency, which was facilitated by two sequential plasmon-coupling-enhanced one-photon absorption steps via real intermediate states. PMID- 26282971 TI - Discontinuous Bubble Nucleation Due to a Metastable Condensation Transition in Polymer-CO2 Mixtures. AB - We combine a newly developed density-functional theory with the string method to calculate the minimum free energy path of bubble nucleation in compressible polymer-CO2 mixtures. Nucleation is initiated by saturating the polymer liquid with high pressure CO2 and subsequently reducing the pressure to ambient condition. Below a critical temperature, we find that there is a discontinuous drop in the nucleation barrier with increased initial CO2 pressure, as a result of an underlying metastable transition from a CO2-rich-vapor phase to a CO2-rich liquid phase. This phenomenon is different from previously proposed nucleation mechanisms involving metastable transitions. PMID- 26282972 TI - Solvent Effects on Vibronic Coupling in a Flexible Bichromophore: Electronic Localization and Energy Transfer induced by a Single Water Molecule. AB - Size and conformation-specific ultraviolet and infrared spectra are used to probe the effects of binding a single water molecule on the close-lying excited states present in a model flexible bichromophore, 1,2-diphenoxyethane (DPOE). The water molecule binds to DPOE asymmetrically, thereby localizing the two electronically excited states on one or the other ring, producing a S1/S2 splitting of 190 cm( 1). Electronic localization is reflected clearly in the OH stretch transitions in the excited states. Since the S2 origin is imbedded in vibronic levels of the S1 manifold, its OH stretch spectrum reflects the vibronic coupling between these levels, producing four OH stretch transitions that are a sum of contributions from S2-localized and S1-localized excited states. The single solvent water molecule thus plays multiple roles, localizing the electronic excitation in the bichromophore, inducing electronic energy transfer between the two rings, and reporting on the state mixing via its OH stretch absorptions. PMID- 26282973 TI - Five Stereoactive Orbitals on Silicon: Charge and Spin Localization in the n Si4Me10(-*) Radical Anion by Trigonal Bipyramidalization. AB - RIUMP2/def2-TZVPPD calculations show that in addition to its usual conformation with charge and spin delocalized over the Si backbone, the isolated Si4Me10(-*) radical anion also has isomeric conformations with localized charge and spin. A structure with localization on a terminal Si atom has been examined in detail. In vacuum, it is calculated to lie 11.5 kcal/mol higher in energy than the charge and-spin delocalized conformation, and in water the difference is as little as 1.6 kcal/mol. According to natural orbital and localized orbital analyses, the charge-and-spin-carrying terminal Si atom uses five stereoactive hybrid orbitals in a trigonal bipyramidal geometry. Four are built mostly from 3s and 3p atomic orbitals (AOs) and are used to attach a Si3(CH3)7 and three CH3 groups, whereas the larger equatorial fifth orbital is constructed from 4s and 4p AOs and acts as a nonbonding (radical) hybrid orbital with an occupancy of about 0.65 e. PMID- 26282974 TI - Vibrational Sum Frequency Generation by the Quadrupolar Mechanism at the Nonpolar Benzene/Air Interface. AB - The interface selectivity of vibrational sum frequency generation (VSFG) spectroscopy is explained under the dipole approximation as resulting from the breakdown of inversion symmetry at the interface. From this viewpoint, VSFG is not expected to occur at the interface consisting of centrosymmetric molecules, because the inversion symmetry is preserved even at the interface. In reality, however, VSFG at the nonpolar benzene/air interface has been observed with traditional homodyne-detected VSFG. Here we report a heterodyne-detected VSFG study of the benzene/air interface. The result strongly indicates that VSFG at this interface cannot be explained within the framework of the dipole approximation. The selection rule and polarization dependence of the observed VSFG signal show that the quadrupole transition plays an essential role because of the field discontinuity at the interface. This finding implies the applicability of interface-selective VSFG to the nonpolar interfaces comprising centrosymmetric molecules, which opens a new possibility of VSFG spectroscopy. PMID- 26282975 TI - Homogeneous Liquid-Liquid Extraction of Metal Ions with a Functionalized Ionic Liquid. AB - Binary mixtures of the ionic liquid betainium bis(trifluoromethylsulfonyl)imide and water show an upper critical solution temperature. This solvent system has been used to extract metal ions by phase-transition extraction, using zwitterionic betaine as extractant. The system is efficient for the extraction of trivalent rare-earth, indium and gallium ions. This new type of metal extraction system avoids problems associated with the use of viscous ionic liquids, namely, the difficulty of intense mixing of the aqueous and ionic liquid phases by stirring. PMID- 26282976 TI - Understanding Li(+)-Solvent Interaction in Nonaqueous Carbonate Electrolytes with (17)O NMR. AB - To understand how Li(+) interacts with individual carbonate molecules in nonaqueous electrolytes, we conducted natural abundance (17)O NMR measurements on electrolyte solutions of 1 M LiPF6 in a series of binary solvent mixtures of ethylene carbonate (EC) and dimethyl carbonate (DMC). It was observed that the largest changes in (17)O chemical shift occurred at the carbonyl oxygens of EC, firmly establishing that Li(+) strongly prefers EC over DMC in typical nonaqueous electrolytes, while mainly coordinating with carbonyl rather than ethereal oxygens. Further quantitative analysis of the displacements in (17)O chemical shifts renders a detailed Li(+)-solvation structure in these electrolyte solutions, revealing that maximum six EC molecules can coexist in the Li(+) solvation sheath, while DMC association with Li(+) is more "noncommittal" but simultaneously prevalent. This discovery, while aligning well with previous fragmental knowledge about Li(+)-solvation, reveals for the first time a complete picture of Li(+) solvation structure in nonaqueous electrolytes. PMID- 26282977 TI - Reaching a Uniform Accuracy for Complex Molecular Systems: Long-Range-Corrected XYG3 Doubly Hybrid Density Functional. AB - An unbiased understanding of complex molecular systems from first-principles critically demands theoretical methods with uniform accuracy for diverse interactions with different natures covering short-, medium-, and long-range correlations. Among the state-of-the-art density functional approximations (DFAs), doubly hybrid (DH) DFAs (e.g., XYG3 in this Letter) provide a remarkable improvement over the conventional DFAs (e.g., B3LYP in this Letter). Even though XYG3 works quite well in many cases of noncovalent bonding interactions (NCIs), it is incomplete in describing the pure long-range dispersive interactions. Here, we address such concerns by adding a scaled long-range contribution from the second-order perturbation theory (PT2). The long-range-corrected XYG3 (lrc-XYG3) is proposed without reparameterizing the three parameters in the original XYG3. Due to its overall excellent performance for all testing sets constructed for various purposes, lrc-XYG3 is the recommended method, which is expected to provide a balanced description of diverse interactions in complex molecular systems. PMID- 26282978 TI - Ligand-Free, Colloidal, and Luminescent Metal Sulfide Nanocrystals. AB - We report here a different kind of binary and ternary colloidal inorganic nanocrystals, where no capping ligand is used. The surfaces of these ligand-free nanocrystals were designed to exhibit negative charges and, therefore, electrostatically repel each other, forming a colloidal dispersion in a polar solvent. Undoped and Mn-doped ZnxCd1-xS nanocrystals were studied both in solution and close-packed films. While undoped samples exhibit poor luminescence because of surface defects, Mn-doped nanocrystals show strong luminescence both in solution (20% quantum efficiency) and the film. Strong Mn emission arises from the inner-core d electrons, which are less sensitive to nonradiative decay channels on the nanocrystal surface. Ligand-free AgInS2 nanocrystals exhibit donor-acceptor type luminescence. Our preliminary results suggest the possibility of electronic coupling between ligand-free nanocrystals in their film, and therefore, they are expected to be more suitable for electronic and optoelectronic applications compared to organic-capped nanocrystals. PMID- 26282979 TI - Dye Sensitized Solar Cells for Economically Viable Photovoltaic Systems. AB - TiO2 nanoparticle-based dye sensitized solar cells (DSSCs) have attracted a significant level of scientific and technological interest for their potential as economically viable photovoltaic devices. While DSSCs have multiple benefits such as material abundance, a short energy payback period, constant power output, and compatibility with flexible applications, there are still several challenges that hold back large scale commercialization. Critical factors determining the future of DSSCs involve energy conversion efficiency, long-term stability, and production cost. Continuous advancement of their long-term stability suggests that state-of-the-art DSSCs will operate for over 20 years without a significant decrease in performance. Nevertheless, key questions remain in regards to energy conversion efficiency improvements and material cost reduction. In this Perspective, the present state of the field and the ongoing efforts to address the requirements of DSSCs are summarized with views on the future of DSSCs. PMID- 26282980 TI - To Hop or Not to Hop? Understanding the Temperature Dependence of Spectral Diffusion in Organic Semiconductors. AB - In disordered organic semiconductors, excited states and charges move by hopping in an inhomogeneously broadened density of states, thereby relaxing energetically ("spectral diffusion"). At low temperatures, transport can become kinetically frustrated and consequently dispersive. Experimentally, this is observed predominantly for triplet excitations and charges, and has not been reported for singlet excitations. We have addressed the origin of this phenomenon by simulating the temperature dependent spectral diffusion using a lattice Monte Carlo approach with either Miller-Abrahams or Forster type transfer rates. Our simulations are in agreement with recent fluorescence and phosphorescence experimental results. We show that frustrated and thus dispersive diffusion appears when the number of available hopping sites is limited. This is frequently the case for triplets that transfer by a short-range interaction, yet may also occur for singlets in restricted geometries or dilute systems. Frustration is lifted when more hopping sites become available, e.g., for triplets as a result of an increased conjugation in some amorphous polymer films. PMID- 26282981 TI - Theory of Covalent Adsorbate Frontier Orbital Energies on Functionalized Light Absorbing Semiconductor Surfaces. AB - Functional hybrid interfaces between organic molecules and semiconductors are central to many emerging information and solar energy conversion technologies. Here we demonstrate a general, empirical parameter-free approach for computing and understanding frontier orbital energies - or redox levels - of a broad class of covalently bonded organic-semiconductor surfaces. We develop this framework in the context of specific density functional theory (DFT) and many-body perturbation theory calculations, within the GW approximation, of an exemplar interface, thiophene-functionalized silicon (111). Through detailed calculations taking into account structural and binding energetics of mixed-monolayers consisting of both covalently attached thiophene and hydrogen, chlorine, methyl, and other passivating groups, we quantify the impact of coverage, nonlocal polarization, and interface dipole effects on the alignment of the thiophene frontier orbital energies with the silicon band edges. For thiophene adsorbate frontier orbital energies, we observe significant corrections to standard DFT (~1 eV), including large nonlocal electrostatic polarization effects (~1.6 eV). Importantly, both results can be rationalized from knowledge of the electronic structure of the isolated thiophene molecule and silicon substrate systems. Silicon band edge energies are predicted to vary by more than 2.5 eV, while molecular orbital energies stay similar, with the different functional groups studied, suggesting the prospect of tuning energy alignment over a wide range for photoelectrochemistry and other applications. PMID- 26282982 TI - Separating Charges at Organic Interfaces: Effects of Disorder, Hot States, and Electric Field. AB - Charge separation at organic-organic (O-O) interfaces is crucial to how many organic-based optoelectronic devices function. However, the mechanism of formation of spatially separated charge carriers and the role of geminate recombination remain topics of discussion and research. We review critically the contributions of the various factors, including electric fields, long-range order, and excess energy (beyond the minimum needed for photoexcitation), to the probability that photogenerated charge carriers will be separated. Understanding the processes occurring at the O/O interface and their relative importance for effective charge separation is crucial to design efficient solar cells and photodetectors. We stress that electron and hole delocalization after photoinduced charge transfer at the interface is important for efficient free carrier generation. Fewer defects at the interface and long-range order in the materials also improve overall current efficiency in solar cells. In efficient organic cells, external electric fields play only a small role for charge separation. PMID- 26282983 TI - Some Insight into Stability of Amorphous Poly(ethylene glycol) Dimethyl Ether Polymers Based on Molecular Dynamics Simulations. AB - Poly(ethylene glycol) dimethyl ether (PEGDME) polymers are widely used as drug solid dispersion reagents. They can cause the amorphization of drugs and improve their solubility, stability, and bioavailability. However, the mechanism about why amorphous PEGDME 2000 polymer is highly stable is unclear so far. Molecular dynamics (MD) simulation is a unique key technique to solve it. In the current work, we systematically investigate structure, aggregate state, and thermodynamic and kinetic behaviors during the phase-transition processes of the PEGDME polymers with different polymerization degree in terms of MD simulations. The melting and glass-transition temperatures of the polymers are in good agreement with experimental values. The amorphous PEGDME2000 exhibits high stability, which is consistent with the recent experiment results and can be ascribed to a combination of two factors, that is, a high thermodynamic driving force for amorphization and a relatively low molecular mobility. PMID- 26282985 TI - Energy Outlook for Planet Earth. PMID- 26282984 TI - Statistical Mechanics of Multilayer Sorption: Surface Tension. AB - Mathematical models of surface tension as a function of solute concentration are needed for predicting the behavior of surface processes relevant to the environment, biology, and industry. Current aqueous surface tension-activity models capture either solutions of electrolytes or those of nonelectrolytes, but a single equation has not yet been found that represents both over the full range of compositions. In prior work, we developed an accurate model of the activity concentration relationship in solutions over the full range of compositions by extending the BET (Brunauer, Emmett, Teller) and GAB (Guggenheim, Anderson, de Boer) isotherms to multiple monolayers of solvent molecules sorbed to solutes. Here, we employ similar statistical mechanical tools to develop a simple equation for the surface tension-activity relationship that differs remarkably from prior formulations in that it (1) works equally well for nonelectrolyte and electrolyte solutes and (2) is accurate over the full range of concentrations from pure solvent to pure solute. PMID- 26282986 TI - Nanoscale Multilayer Transition-Metal Dichalcogenide Heterostructures: Band Gap Modulation by Interfacial Strain and Spontaneous Polarization. AB - Using density functional theory calculations, we unveil intriguing electronic properties of nanoscale multilayer transition-metal dichalcogenide (TMDC) heterostructures, (MoX2)n(MoY2)m (X, Y = S, Se or Te). Our results show that the structural stability and electronic band structure of the TMDC heterostructures depend sensitively on the choice of constituent components and their relative thickness. In particular, the electronic band gap can be tuned over a wide range by the intrinsic mismatch strain and spontaneous electrical polarization at the interface of the heterostructures, which suggests desirable design strategies for TMDC-based devices with an easily adjustable band gap. These interfacial effects also make the electronic properties more susceptible to the influence of a bias electric field, which can induce sensitive and considerable changes in the band gap and even produce a semiconductor-metal transition at relatively low electric fields. Such effective electronic band gap engineering via a combination of internal (i.e., the composition and layer thickness) and external (i.e., a bias field) control makes the TMDC-based heterostructures promising candidates for applications in a variety of nanodevices. PMID- 26282987 TI - Feasibility of Lithium Storage on Graphene and Its Derivatives. AB - Nanomaterials are anticipated to be promising storage media, owing to their high surface-to-mass ratio. The high hydrogen capacity achieved by using graphene has reinforced this opinion and motivated investigations of the possibility to use it to store another important energy carrier - lithium (Li). While the first principles computations show that the Li capacity of pristine graphene, limited by Li clustering and phase separation, is lower than that offered by Li intercalation in graphite, we explore the feasibility of modifying graphene for better Li storage. It is found that certain structural defects in graphene can bind Li stably, yet a more efficacious approach is through substitution doping with boron (B). In particular, the layered C3B compound stands out as a promising Li storage medium. The monolayer C3B has a capacity of 714 mAh/g (as Li1.25C3B), and the capacity of stacked C3B is 857 mAh/g (as Li1.5C3B), which is about twice as large as graphite's 372 mAh/g (as LiC6). Our results help clarify the mechanism of Li storage in low-dimensional materials, and shed light on the rational design of nanoarchitectures for energy storage. PMID- 26282988 TI - Triple-Decker Motif for Red-Shifted Fluorescent Protein Mutants. AB - Among fluorescent proteins (FPs) used as genetically encoded fluorescent tags, the red-emitting FPs are of particular importance as suitable markers for deep tissue imaging. Using electronic structure calculations, we predict a new structural motif for achieving red-shifted absorption and emission in FPs from the GFP family. By introducing four point mutations, we arrive to the structure with the conventional anionic GFP chromophore sandwiched between two tyrosine residues. Contrary to the existing red FPs in which the red shift is due to extended conjugation of the chromophore, in the triple-decker motif, the chromophore is unmodified and the red shift is due to pi-stacking interactions. The absorption/emission energies of the triple-decker FP are 2.25/2.16 eV, respectively, which amounts to shifts of ~40 (absorption) and ~25 nm (emission) relative to the parent species, the I form of wtGFP. Using a different structural motif based on a smaller chromophore may help to improve optical output of red FPs by reducing losses due to radiationless relaxation and photobleaching. PMID- 26282989 TI - Measurements of Light Extinction by Single Aerosol Particles. AB - A Bessel beam optical trap is combined with continuous wave cavity ringdown spectroscopy to measure the extinction cross section of individual aerosol particles. Particles, ~1 MUm in size, can be captured indefinitely and processes that transform size or refractive index studied. The measured light extinction induced by the particle is shown to depend on the position of the particle in the cavity, allowing accurate measurements of the mode structure of a high finesse optical cavity without significant perturbation. The variation in extinction efficiency of a sodium chloride droplet with relative humidity is shown to agree well with predictions from Mie scattering theory. PMID- 26282990 TI - Revealing the Electronic and Molecular Structure of Randomly Oriented Molecules by Polarized Two-Photon Spectroscopy. AB - In this Letter, we explored the use of polarized two-photon absorption (2PA) spectroscopy, which brings additional information when compared to methods that do not use polarization control, to investigate the electronic and molecular structure of two chromophores (FD43 and FD48) based on phenylacetylene moieties. The results were analyzed using quantum chemical calculations of the two-photon transition strengths for circularly and linearly polarized light, provided by the response function formalism. On the basis of these data, it was possible to distinguish and identify the excited electronic states responsible for the lowest energy 2PA-allowed band in both chromophores. By modeling the 2PA circular-linear dichroism, within the sum-over-essential states approach, we obtained the relative orientation between the dipole moments that are associated with the molecular structure of the chromophores in solution. This result allowed to correlate the V-shape structure of the FD48 chromophore and the quantum interference-modulated 2PA strength. PMID- 26282992 TI - R.Graham Cooks. PMID- 26282991 TI - Phylogenomic and functional analyses of salmon lice aquaporins uncover the molecular diversity of the superfamily in Arthropoda. AB - BACKGROUND: An emerging field in biomedical research is focusing on the roles of aquaporin water channels in parasites that cause debilitating or lethal diseases to their vertebrate hosts. The primary vectorial agents are hematophagous arthropods, including mosquitoes, flies, ticks and lice, however very little is known concerning the functional diversity of aquaporins in non-insect members of the Arthropoda. Here we conducted phylogenomic and functional analyses of aquaporins in the salmon louse, a marine ectoparasitic copepod that feeds on the skin and body fluids of salmonids, and used the primary structures of the isolated channels to uncover the genomic repertoires in Arthropoda. RESULTS: Genomic screening identified 7 aquaporin paralogs in the louse in contrast to 42 in its host the Atlantic salmon. Phylogenetic inference of the louse nucleotides and proteins in relation to orthologs identified in Chelicerata, Myriapoda, Crustacea and Hexapoda revealed that the arthropod aquaporin superfamily can be classified into three major grades (1) classical aquaporins including Big brain (Bib) and Prip-like (PripL) channels (2) aquaglyceroporins (Glp) and (3) unorthodox aquaporins (Aqp12-like). In Hexapoda, two additional subfamilies exist as Drip and a recently classified entomoglyceroporin (Eglp) group. Cloning and remapping the louse cDNAs to the genomic DNA revealed that they are encoded by 1 7 exons, with two of the Glps being expressed as N-terminal splice variants (Glp1_v1, -1_v2, -3_v1, -3_v2). Heterologous expression of the cRNAs in amphibian oocytes demonstrated that PripL transports water and urea, while Bib does not. Glp1_v1, -2, -3_v1 and -3_v2 each transport water, glycerol and urea, while Glp1_v2 and the Aqp12-like channels were retained intracellularly. Transcript abundance analyses revealed expression of each louse paralog at all developmental stages, except for glp1_v1, which is specific to preadult and adult males. CONCLUSIONS: Our data suggest that the aquaporin repertoires of extant arthropods have expanded independently in the different lineages, but can be phylogenetically classified into three major grades as opposed to four present in deuterostome animals. While the aquaporin repertoire of Atlantic salmon represents a 6-fold redundancy compared to the louse, the functional assays reveal that the permeation properties of the different crustacean grades of aquaporin are largely conserved to the vertebrate counterparts. PMID- 26282993 TI - MicroRNA-132 promotes estradiol synthesis in ovarian granulosa cells via translational repression of Nurr1. AB - BACKGROUND: Estrogen synthesis is an important function of the mammalian ovary. Estrogen plays important roles in many biological processes, including follicular development, oocyte maturation and endometrial proliferation, and dysfunctions in estrogen synthesis contribute to the development of polycystic ovary syndrome and premature ovarian failure. Classical signaling cascades triggered by follicle stimulating hormone induce estrogen synthesis via the upregulation of Cyp19a1 in granulosa cells (GCs). This study aimed to determine the effect of microRNA-132 (miR-132) on estradiol synthesis in GCs. METHODS: Primary mouse GCs were collected from ovaries of 21-day-old immature ICR mice through follicle puncture. GCs were cultured and treated with the stable cyclic adenosine monophosphate analog 8-Br-cAMP or transfected with miR-132 mimics, Nurr1-specific small interfering RNA oligonucleotides and Flag-Nurr1 plasmids. Concentrations of estradiol and progesterone in culture medium were determined by an automated chemiluminescence-based assay. Quantitative real time PCR and western blot were performed to identify the effect of miR-132 on Cyp19a1, Cyp11a1 and an orphan nuclear receptor-Nurr1 expression in GCs. Direct suppression of Nurr1 via its 3' untranslated region by miR-132 were further verified using luciferase reporter assays. RESULTS: The expression level of miR-132 in cultured mouse GCs was significantly elevated during 48 h of treatment with 8-Br-cAMP. The synthesis of estradiol increased after the overexpression of miR-132 in mouse GCs. The real time PCR results demonstrated that miR-132 induced the expression of Cyp19a1 significantly. Nurr1, an orphan nuclear receptor that suppresses Cyp19a1 expression, was found to be a direct target of miR-132. Nurr1 was suppressed by miR-132, as indicated by a luciferase assay and Western blotting. The knockdown of Nurr1 primarily elevated the synthesis of estradiol and partially attenuated the miR-132-induced estradiol elevation, and the ectopic expression of Flag-Nurr1 abrogated the stimulatory effect of miR-132 on estradiol synthesis in mouse GCs. CONCLUSIONS: Our findings suggest that miR-132 is involved in the cAMP signaling pathway and promotes estradiol synthesis via the translational repression of Nurr1 in ovarian GCs. PMID- 26282994 TI - Shallow whole genome sequencing is well suited for the detection of chromosomal aberrations in human blastocysts. AB - OBJECTIVE: To add evidence that massive parallel sequencing (MPS) is a valuable substitute for array comparative genomic hybridization (arrayCGH) with a resolution that is more appropriate for preimplantation genetic diagnosis (PGD) in translocation carriers. DESIGN: Study of diagnostic accuracy. SETTING: University hospital. PATIENT(S): Fifteen patients with a balanced structural rearrangement were included in the study: eight reciprocal translocations, four Robertsonian translocations, two inversions, and one insertional translocation. INTERVENTION(S): Trophectoderm biopsy was performed on 47 blastocysts. MAIN OUTCOME MEASURE(S): In the current study, shallow whole genome MPS on a NextSeq500 (Illumina) and Ion Proton (Life Technologies) instrument was performed in parallel on 47 whole genome amplified trophectoderm samples. Data analyses were performed using the QDNAseq algorithm implemented in Vivar. RESULT(S): In total, 5 normal and 42 abnormal embryos were analyzed. All aberrations previously detected with arrayCGH could be readily detected in the MPS data using both technologies and were correctly identified. The smallest detected abnormality was a ~ 4.5 Mb deletion/duplication. CONCLUSION(S): This study demonstrates that shallow whole genome sequencing can be applied efficiently for the detection of numerical and structural chromosomal aberrations in embryos, equaling or even exceeding the resolution of the routinely used microarrays. PMID- 26282995 TI - Galectin-8 promotes regulatory T-cell differentiation by modulating IL-2 and TGFbeta signaling. AB - Galectins (Gals) have emerged as potent immunoregulatory molecules that control chronic inflammation through distinct mechanisms. Gal-8, a tandem-repeat type Gal with unique preference for alpha2,3-sialylated glycans, is ubiquitously expressed, but little is known about its role in T-cell differentiation. Here we report that Gal-8 promotes the polyclonal differentiation of primary mouse regulatory T (Treg) cells in vitro. We further show that Gal-8 also facilitates antigen-specific differentiation of Treg cells, and that Treg cells polarized in the presence of Gal-8 express cytotoxic T-lymphocyte antigen-4 and interleukin (IL)-10 at a higher frequency than control Treg cells, and efficiently inhibit proliferation of activated T-cells in vitro. Investigation of the mechanism by which Gal-8 promotes Treg conversion revealed that Gal-8 activates transforming growth factor-beta signaling and promotes sustained IL-2R signaling. Taken together, these data suggest that Gal-8 promotes the differentiation of highly suppressive Treg cells, which has implications for the treatment of inflammatory and autoimmune diseases. PMID- 26282997 TI - SNP Set Association Testing for Survival Outcomes in the Presence of Intrafamilial Correlation. AB - In this work, we propose a single nucleotide polymorphism (SNP) set association test for censored phenotypes in the presence of a family-based design. The proposed test is valid for both common and rare variants. A proportional hazards Cox model is specified for the marginal distribution of the trait and the familial dependence is modeled via a Gaussian copula. Censored values are treated as partially missing data and a multiple imputation procedure is proposed in order to compute the test statistics. The P-value is then deduced analytically. The finite-sample empirical properties of the proposed method are evaluated and compared to existing competitors by simulations and its use is illustrated using a breast cancer data set from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2. PMID- 26282996 TI - Sequence Kernel Association Analysis of Rare Variant Set Based on the Marginal Regression Model for Binary Traits. AB - Recent sequencing efforts have focused on exploring the influence of rare variants on the complex diseases. Gene level based tests by aggregating information across rare variants within a gene have become attractive to enrich the rare variant association signal. Among them, the sequence kernel association test (SKAT) has proved to be a very powerful method for jointly testing multiple rare variants within a gene. In this article, we explore an alternative SKAT. We propose to use the univariate likelihood ratio statistics from the marginal model for individual variants as input into the kernel association test. We show how to compute its significance P-value efficiently based on the asymptotic chi-square mixture distribution. We demonstrate through extensive numerical studies that the proposed method has competitive performance. Its usefulness is further illustrated with application to associations between rare exonic variants and type 2 diabetes (T2D) in the Atherosclerosis Risk in Communities (ARIC) study. We identified an exome-wide significant rare variant set in the gene ZZZ3 worthy of further investigations. PMID- 26282998 TI - A Novel Statistic for Global Association Testing Based on Penalized Regression. AB - Natural genetic structures like genes may contain multiple variants that work as a group to determine a biologic outcome. The effect of rare variants, mutations occurring in less than 5% of samples, is hypothesized to be explained best as groups collectively associated with a biologic function. Therefore, it is important to develop powerful association tests to identify a true association between an outcome of interest and a group of variants, in particular a group with many rare variants. In this article we first delineate a novel penalized regression-based global test for the association between sets of variants and a disease phenotype. Next, we use Genetic Analysis Workshop 18 (GAW18) data to assess the power of the new global association test to capture a relationship between an aggregated group of variants and a simulated hypertension status. Rare variant only, common variant only, and combined variant groups are studied. The power values are compared to those obtained from eight well-regarded global tests (Score, Sum, SSU, SSUw, UminP, aSPU, aSPUw, and sequence kernel association test (SKAT)) that do not use penalized regression and a set of tests using either the SSU or score statistics and least absolute shrinkage and selection operator penalty (LASSO) logistic regression. Association testing of rare variants with our method was the top performer when there was low linkage disequilibrium (LD) between and within causal variants. This was similarly true when simultaneously testing rare and common variants in low LD scenarios. Finally, our method was able to provide meaningful variant-specific association information. PMID- 26283000 TI - Associations of prognostic awareness/acceptance with psychological distress, existential suffering, and quality of life in terminally ill cancer patients' last year of life. AB - PURPOSE: Whether prognostic awareness benefits terminally ill cancer patients' psychological-existential well-being and quality of life (QOL) is unclear because of lack of well-controlled longitudinal studies. This study longitudinally evaluated the associations of accurate prognostic awareness and prognostic acceptance with psychological distress, existential suffering, and QOL while comprehensively controlling for confounders in Taiwanese terminally ill cancer patients' last year of life. PATIENTS AND METHODS: A convenience sample of 325 cancer patients was followed until death. Psychological distress and existential suffering were assessed by severe anxiety and depressive symptoms and high self perceived sense of burden to others, respectively. Dichotomized and continuous (QOL) outcome variables were evaluated by multivariate logistic and linear regression modeling with the generalized estimating equation, respectively. RESULTS: Accurate prognostic awareness was not associated with the likelihood of severe anxiety or depressive symptoms but significantly increased the likelihood of high self-perceived sense of burden to others and was associated with poorer QOL in participants' last year of life. Participants who knew and highly accepted their prognosis were significantly less likely to experience severe anxiety symptoms than those who were unaware of or knew their prognosis but had difficulty accepting it. CONCLUSION: Knowing one's poor prognosis and confronting one's impending death without full acceptance and adequate professional psycho spiritual support may harm more than benefit terminally ill cancer patients' psychological state, existential well-being, and QOL. These findings highlight the importance of tailoring psycho-spiritual support to cancer patients' psychological and existential needs when prognostic information is disclosed. PMID- 26283003 TI - The making of a Barr body: the mosaic of factors that eXIST on the mammalian inactive X chromosome. AB - During X-chromosome inactivation (XCI), nearly an entire X chromosome is permanently silenced and converted into a Barr body, providing dosage compensation for eutherians between the sexes. XCI is facilitated by the upregulation of the long non-coding RNA gene, XIST, which coats its chromosome of origin, recruits heterochromatin factors, and silences gene expression. During XCI, at least two distinct types of heterochromatin are established, and in this review we discuss the enrichment of facultative heterochromatin marks such as H3K27me3, H2AK119ub, and macroH2A as well as pericentric heterochromatin marks such as HP1, H3K9me3, and H4K20me3. The extremely stable maintenance of silencing is a product of reinforcing interactions within and between these domains. This paper "Xplores" the current knowledge of the pathways involved in XCI, how the pathways interact, and the gaps in our understanding that need to be filled. PMID- 26283004 TI - A shift in anterior-posterior positional information underlies the fin-to-limb evolution. AB - The pectoral fins of ancestral fishes had multiple proximal elements connected to their pectoral girdles. During the fin-to-limb transition, anterior proximal elements were lost and only the most posterior one remained as the humerus. Thus, we hypothesised that an evolutionary alteration occurred in the anterior posterior (AP) patterning system of limb buds. In this study, we examined the pectoral fin development of catshark (Scyliorhinus canicula) and revealed that the AP positional values in fin buds are shifted more posteriorly than mouse limb buds. Furthermore, examination of Gli3 function and regulation shows that catshark fins lack a specific AP patterning mechanism, which restricts its expression to an anterior domain in tetrapods. Finally, experimental perturbation of AP patterning in catshark fin buds results in an expansion of posterior values and loss of anterior skeletal elements. Together, these results suggest that a key genetic event of the fin-to-limb transformation was alteration of the AP patterning network. PMID- 26283005 TI - Exposure to war traumatic experiences, post-traumatic stress disorder and post traumatic growth among nurses in Gaza. AB - ACCESSIBLE SUMMARY: What is known on the subject? This study builds on existing research on war-related factors that may affect health-care staff by particularly focusing on trauma exposure in both professional and everyday life, as well as on correlates of later positive psychological changes. What this paper adds to existing knowledge? It shows that one in five nursing staff working in Gaza experienced post-traumatic stress symptoms within the clinical range, 2 years after an incursion on Gaza and after being exposed to substantial trauma during this period. Participants appeared to develop a variety of post-traumatic growth responses following trauma exposure. Although nurses experienced traumatic events both as civilians and in their health-care capacity, personal exposure was strongly associated with PTSD symptoms. What are the implications for practice? Support to nursing and other health-care professionals in war situations should entail different levels, remain available well after an acute conflict, and take into consideration both personal and practice-related traumatic events. Mental health nursing practitioners can play a pivotal role in this. ABSTRACT: AIM: To establish the association between war traumatic experiences, post-traumatic stress disorder (PTSD) symptoms and post-traumatic growth among nurses in the Gaza Strip, 2 years after an incursion on Gaza, and during a period of ongoing trauma exposure. This study builds on existing evidence by considering exposure to personal and work-related traumatic events, and on factors associated with later positive psychological adaptation. METHODS: The sample consisted of 274 randomly selected nurses in Gaza who completed the Gaza Traumatic Events Checklist, PTSD Checklist, and Posttraumatic Growth Inventory. RESULTS: Of the nurses, 19.7% reported full PTSD. There was a significant relationship between traumatic events and PTSD scores; as well as between community-related traumatic events and post-traumatic growth. Participants reported a range of traumatic events, but PTSD and post-traumatic growth scores were more strongly associated with community rather than work-related traumas. DISCUSSION: Nursing professionals experienced high levels of distress 2 years following an acute period of conflict, both as civilians and in their health-care capacity. IMPLICATIONS FOR PRACTICE: There is need for different levels of support for health-care staff in war-affected areas. Mental health nursing professionals have a central role in training, counselling and support to other health-care colleagues. PMID- 26283001 TI - Spontaneous gesture and spatial language: Evidence from focal brain injury. AB - People often use spontaneous gestures when communicating spatial information. We investigated focal brain-injured individuals to test the hypotheses that (1) naming motion event components of manner-path (represented by verbs-prepositions in English) are impaired selectively, (2) gestures compensate for impaired naming. Patients with left or right hemisphere damage (LHD or RHD) and elderly control participants were asked to describe motion events (e.g., running across) depicted in brief videos. Damage to the left posterior middle frontal gyrus, left inferior frontal gyrus, and left anterior superior temporal gyrus (aSTG) produced impairments in naming paths of motion; lesions to the left caudate and adjacent white matter produced impairments in naming manners of motion. While the frequency of spontaneous gestures were low, lesions to the left aSTG significantly correlated with greater production of path gestures. These suggest that producing prepositions-verbs can be separately impaired and gesture production compensates for naming impairments when damage involves left aSTG. PMID- 26283006 TI - Ants medicate to fight disease. AB - Parasites are ubiquitous, and the ability to defend against these is of paramount importance. One way to fight diseases is self-medication, which occurs when an organism consumes biologically active compounds to clear, inhibit, or alleviate disease symptoms. Here, we show for the first time that ants selectively consume harmful substances (reactive oxygen species, ROS) upon exposure to a fungal pathogen, yet avoid these in the absence of infection. This increased intake of ROS, while harmful to healthy ants, leads to higher survival of exposed ants. The fact that ingestion of this substance carries a fitness cost in the absence of pathogens rules out compensatory diet choice as the mechanism, and provides evidence that social insects medicate themselves against fungal infection, using a substance that carries a fitness cost to uninfected individuals. PMID- 26283007 TI - Clinicopathological Significance and Potential Drug Target of CDKN2A/p16 in Endometrial Carcinoma. AB - Previous studies demonstrated that the loss of function of the CDKN2A/p16/INK4A gene is mainly caused by the hypermethylation of CDKN2A, however, whether or not it is associated with the incidence and clinicopathological characteristics of endometrial carcinoma (EC) remains unclear. In this study, we conducted a meta analysis aiming to comprehensively assess the role of CDKN2A hypermethylation in the pathogenesis of EC. A detailed literature search was made to identify the related research publications. Analysis of pooled data was performed. Odds ratio (OR) was calculated and summarized. Final analysis of 638 EC patients from 12 eligible studies was performed. The results showed that CDKN2A hypermethylation was significantly higher in EC than in normal control tissue, the pooled OR from 8 studies including 400 EC patients and 131 controls, OR = 8.39 with 95% CI 4.03 17.45, test for overall effect, Z = 5.69, P < 0.00001. Further analysis showed that CDKN2A hypermethylation was not significantly associated with tumor differentiation and clinical stage status in EC patients. The results of this meta-analysis suggest that CDKN2A hypermethylation may be implicated in the pathogenesis of EC. CDKN2A hypermethylation was not significantly associated with tumor differentiation and clinical stage status in EC patients, indicating that CDKN2A hypermethylation might be early event of EC. PMID- 26283008 TI - Genetic influences on dental enamel that impact caries differ between the primary and permanent dentitions. AB - Clinically, primary and permanent teeth are distinct anatomically and the presentation of caries lesions differs between the two dentitions. Hence, the possibility exists that genetic contributions to tooth formation of the two dentitions are different. The purpose of this study was to test the hypothesis that genetic associations with an artificial caries model will not be the same between primary and permanent dentitions. Enamel samples from primary and permanent teeth were tested for microhardness at baseline, after carious lesion creation, and after fluoride application to verify association with genetic variants of selected genes. Associations were found between genetic variants of ameloblastin, amelogenin, enamelin, tuftelin, tuftelin interactive protein 11, and matrix metallopeptidase 20 and enamel from permanent teeth but not with enamel from primary teeth. In conclusion, our data continue to support that genetic variation may impact enamel development and consequently individual caries susceptibility. These effects may be distinct between primary and permanent dentitions. PMID- 26283009 TI - Is There Another Bite of the Cherry? The Case for Radical Local Therapy for Oligometastatic Disease in Prostate Cancer. PMID- 26283010 TI - Robotic Partial Nephrectomy: The Will Rogers Surgical Effect. AB - Comparison of surgical techniques must be critically and objectively evaluated, ideally in the context of prospective trials. Comprehensive surgical training ensures that patients are offered the most appropriate treatment and highest clinical care. PMID- 26283011 TI - A Multicenter Randomized Noninferiority Trial Comparing GreenLight-XPS Laser Vaporization of the Prostate and Transurethral Resection of the Prostate for the Treatment of Benign Prostatic Obstruction: Two-yr Outcomes of the GOLIATH Study. AB - BACKGROUND: The GOLIATH study is a 2-yr trial comparing transurethral resection of prostate (TURP) to photoselective vaporization with the GreenLight XPS Laser System (GL-XPS) for the treatment of benign prostatic obstruction (BPO). Noninferiority of GL-XPS to TURP was demonstrated based on a 6-mo follow-up from the study. OBJECTIVE: To determine whether treatment effects observed at 6 mo between GL-XPS and TURP was maintained at the 2-yr follow-up. DESIGN, SETTING, AND PARTICIPANTS: Prospective randomized controlled trial at 29 centers in nine European countries involving 281 patients with BPO. INTERVENTION: Photoselective vaporization using the 180-W GreenLight GL-XPS or conventional (monopolar or bipolar) TURP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the International Prostate Symptom Score for which a margin of three was used to evaluate the noninferiority of GL-XPS. Secondary outcomes included Qmax, prostate volume, prostate specific antigen, Overactive Bladder Questionnaire Short Form, International Consultation on Incontinence Questionnaire Short Form, occurrence of surgical retreatment, and freedom from complications. RESULTS AND LIMITATIONS: One hundred and thirty-six patients were treated using GL-XPS and 133 using TURP. Noninferiority of GL-XPS on International Prostate Symptom Score, Qmax, and freedom from complications was demonstrated at 6-mo and was sustained at 2-yr. The proportion of patients complication-free through 24-mo was 83.6% GL XPS versus 78.9% TURP. Reductions in prostate volume and prostate specific antigen were similar in both arms and sustained over the course of the trial. Compared with the 1(st) yr of the study, very few adverse events or retreatments were reported in either arm. Treatment differences in the Overactive Bladder Questionnaire Short Form observed at 12-mo were not statistically significant at 24-mo. A limitation was that patients and treating physicians were not blinded to the therapy. CONCLUSIONS: Twenty-four-mo follow-up data demonstrated that GL-XPS provides a durable surgical option for the treatment of BPO that exhibits efficacy and safety outcomes similar to TURP. PATIENT SUMMARY: The long-term effectiveness and safety of GLP-XLS was similar to conventional TURP for the treatment of prostate enlargement. PMID- 26283012 TI - Human cytomegalovirus-1 and Epstein-Barr virus-1 viral colonization of titanium and zirconia abutments: a split-mouth study. AB - AIM: Human cytomegalovirus-1 (HCMV-1) and Epstein-Barr virus-1 (EBV-1) detection in submarginal plaque is linked to diseased states of the periodontium. In the present study, we evaluated the viral colonization of titanium and zirconia abutments by HCMV-1 and EBV-1 in a split-mouth study. METHODS: Forty dental implant abutments placed in 20 non-smokers were evaluated retrospectively. Each participant had received at least one each of titanium and zirconia abutments (in function for at least 1 year). HCMV-1 and EBV-1 were evaluated in these clinically-healthy peri-implant sites' submarginal plaque biofilm at one titanium and one zirconia abutment, one healthy tooth site, and serum using polymerase chain reaction assays. Related-samples McNemar test and Wilcoxon signed-rank test were used to determine the differences in viral detection frequency and load, respectively. RESULTS: EBV-1 was detected at the titanium abutment in 60% of participants, but in none at their zirconia abutment (P = 0.04). HCMV-1 was detected at the titanium abutments in 90% of participants, and at the zirconia abutments in 70% of participants. This difference was not significant (P = 0.25). The differences in HCMV-1 viral load between the abutment types were insignificant (P = 0.075). CONCLUSION: EBV-1 did not colonize the biofilm at the zirconia abutments as opposed to the titanium abutments in the same participants. Abutment material could contribute to differences in biofilm characteristics. PMID- 26283013 TI - Inactivation of Zika virus in plasma with amotosalen and ultraviolet A illumination. AB - BACKGROUND: Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) transmitted by mosquitoes. The potential for ZIKV transmission through blood transfusion was demonstrated during the ZIKV outbreak that occurred in French Polynesia from October 2013 to April 2014. Pathogen inactivation of blood products is a proactive strategy that provides the potential to reduce transfusion-transmitted diseases. Inactivation of arboviruses by amotosalen and ultraviolet A (UVA) illumination was previously demonstrated for chikungunya, West Nile, and dengue viruses. We report here the efficiency of this process for ZIKV inactivation of human plasma. STUDY DESIGN AND METHODS: Plasma units were spiked with ZIKV. Viral titers and RNA loads were measured in plasma before and after amotosalen and UVA photochemical treatment. RESULTS: The mean ZIKV titers and RNA loads in plasma before inactivation were respectively 6.57 log TCID50 /mL and 10.25 log copies/mL. After inactivation, the mean ZIKV RNA loads was 9.51 log copies/mL, but cell cultures inoculated with inactivated plasma did not result in infected cells and did not produce any replicative virus after one passage, nor detectable viral RNA from the second passage. CONCLUSION: In this study we demonstrate that amotosalen combined with UVA light inactivates ZIKV in fresh-frozen plasma. This inactivation process is of particular interest to prevent plasma transfusion transmitted ZIKV infections in areas such as French Polynesia, where several arboviruses are cocirculating. PMID- 26283014 TI - miR-483-5p and miR-486-5p are down-regulated in cumulus cells of metaphase II oocytes from women with polycystic ovary syndrome. AB - The aim of this study was to compare the expression of microRNAs (miRNAs) in cumulus cells from polycystic ovary syndrome (PCOS) and non-PCOS women. In the present study, miRNA expression profiles of the cumulus cell samples were determined by miRNA microarrays. Quantification of selected miRNAs and predicted target genes was performed using quantitative real-time PCR (qRT-PCR). The results showed that miR-483-5p and miR-486-5p are significantly decreased in cumulus cells of PCOS patients PCOS (fold change >2, false discovery rate <0.001). qRT-PCR found that four predicted genes, SOCS3, SRF, PTEN and FOXO1, were significantly increased in PCOS cumulus cells (all P < 0.001), and IGF2 (host gene of miR-483-5p) was significantly decreased in PCOS cumulus cells (P < 0.001). These results indicated that miR-483-5p might play an important role in reducing insulin resistance, and that miR-486-5p might promote cumulus cell proliferation through activation of PI3K/Akt. The findings from this study provided new insights into the complex molecular mechanisms involved in PCOS by revealing pathways possibly regulated by miRNAs. The differences in miRNAs (miR 483-5p, miR-486-5p) and their target gene expression in cumulus cells may provide clues for future research and help to explain aberrant follicular development and subfertility in women with PCOS. PMID- 26283015 TI - The effect of mode of conception on obstetrical outcomes differs by body mass index. AB - This study compared the odds of adverse obstetrical outcomes of pregnancies in women who conceived from IVF (n = 464) versus spontaneous conception (n = 1171) after stratification into three body mass index (BMI) groups: normal weight (18.5 24.9 kg/m(2)), overweight (25.0-29.9 kg/m(2)) and obese (>30 kg/m(2)). With increasing BMI, incidences of complications between IVF and spontaneously conceived groups narrowed. Among women with normal BMI, IVF pregnancies were associated with increased odds of placental ischaemic disorders (11.3% versus 7.0%, adjusted odds ratio [aOR] = 2.24; 95% confidence interval [CI] = 1.25-4.04) and low birthweight <2500 g (10.6% versus 8.0%, aOR = 2.08; 95% CI = 1.12-3.88). Among overweight women, only low birthweight (<2500 g) was significantly increased (15.6% versus 6.2%, aOR = 4.33; 95%, CI = 1.61-11.63). For obese women, there were no differences between IVF and spontaneously conceived pregnancies for either placental ischaemic disorders (12.5 versus 20.2%, OR = 0.43, 95% CI = 0.17 1.1) or low birthweight (10.0% versus 11.0%, aOR = 0.7, 95% CI = 0.24-2.08). Overall, the odds of adverse obstetrical outcomes were not significantly greater in IVF singleton pregnancies compared with those conceived spontaneously as BMI increased. PMID- 26283017 TI - Assessing ovarian response: antral follicle count versus anti-Mullerian hormone. AB - Oocyte number and quality decline with age; however, fertility varies significantly even among women of the same age. Various measures have been developed to predict response to ovarian stimulation and reproductive potential. Evaluation of ovarian reserve can identify patients who may experience poor response or hyper-response to exogenous gonadotrophins and can aid in the personalization of treatment to achieve good response and minimize risks. In recent years, two key methods, antral follicle count (AFC), an ultrasound biomarker of follicle number, and the concentration of serum anti-Mullerian hormone (AMH), a hormone biomarker of follicle number, have emerged as preferred methods for assessing ovarian reserve. In this review, a live debate held at the American Society for Reproductive Medicine 2013 Annual Meeting is expanded upon to compare the predictive values, merits, and disadvantages of AFC and AMH level. An ovarian reserve measure without limitations has not yet been discovered, although both AFC and AMH have good predictive value. Published evidence, however, as well as the objectivity and potential standardization of AMH level and the convenience of testing any time throughout the menstrual cycle, leans towards AMH level becoming the gold-standard biomarker to evaluate ovarian reserve and predict ovarian response to stimulation. PMID- 26283016 TI - A clinically useful simplified blastocyst grading system. AB - The aim of this study was to investigate whether a new simplified blastocyst grading system (A: fully expanded, clear inner cell mass, cohesive trophectoderm; B: not yet expanded, clear inner cell mass, cohesive trophectoderm; C: small inner cell mass +/- irregular trophectoderm +/- excluded/degenerate cells) was clinically useful. All day-5 single embryo transfers between 15 June 2009 and 29 June 2012 were reviewed. Implantation, clinical pregnancy and live birth rates were related to embryo quality. Five embryologists were asked to grade and decide the clinical fate of 80 images of day-5 embryos on two occasions 4-6 weeks apart. Implantation, clinical pregnancy and live birth rates decreased with deteriorating embryo quality. A highly significant (P < 0.01) difference was observed between the groups. Inter-observer agreement was substantial for grade allocation (K = 0.63) and clinical decision-making (K = 0.66). Intra-observer agreement ranged from substantial (K = 0.71) to almost perfect (K = 0.88) for grade allocation, and was almost perfect for clinical fate determination (K >= 0.84). This grading system is quick and easy to use, effectively predicts IVF outcome and has levels of agreement similar to, if not better than, those associated with more complex grading systems. PMID- 26283018 TI - The Concepts of Risk, Safety, and Security: Applications in Everyday Language. AB - The concepts of risk, safety, and security have received substantial academic interest. Several assumptions exist about their nature and relation. Besides academic use, the words risk, safety, and security are frequent in ordinary language, for example, in media reporting. In this article, we analyze the concepts of risk, safety, and security, and their relation, based on empirical observation of their actual everyday use. The "behavioral profiles" of the nouns risk, safety, and security and the adjectives risky, safe, and secure are coded and compared regarding lexical and grammatical contexts. The main findings are: (1) the three nouns risk, safety, and security, and the two adjectives safe and secure, have widespread use in different senses, which will make any attempt to define them in a single unified manner extremely difficult; (2) the relationship between the central risk terms is complex and only partially confirms the distinctions commonly made between the terms in specialized terminology; (3) whereas most attempts to define risk in specialized terminology have taken the term to have a quantitative meaning, nonquantitative meanings dominate in everyday language, and numerical meanings are rare; and (4) the three adjectives safe, secure, and risky are frequently used in comparative form. This speaks against interpretations that would take them as absolute, all-or-nothing concepts. PMID- 26283019 TI - Trace Element Concentrations in Liver of 16 Species of Cetaceans Stranded on Pacific Islands from 1997 through 2013. AB - The impacts of anthropogenic contaminants on marine ecosystems are a concern worldwide. Anthropogenic activities can enrich trace elements in marine biota to concentrations that may negatively impact organism health. Exposure to elevated concentrations of trace elements is considered a contributing factor in marine mammal population declines. Hawai'i is an increasingly important geographic location for global monitoring, yet trace element concentrations have not been quantified in Hawaiian cetaceans, and there is little trace element data for Pacific cetaceans. This study measured trace elements (Cr, Mn, Cu, Zn, As, Se, Sr, Cd, Sn, Hg, and Pb) in liver of 16 species of cetaceans that stranded on U.S. Pacific Islands from 1997 to 2013, using high resolution inductively coupled plasma mass spectrometry (HR-ICP-MS) (n = 31), and direct mercury analysis atomic absorption spectrometry (DMA-AAS) (n = 43). Concentration ranges (MUg/g wet mass fraction) for non-essential trace elements, such as Cd (0.0031-58.93) and Hg (0.0062-1571.75) were much greater than essential trace elements, such as Mn (0.590-17.31) and Zn (14.72-245.38). Differences were found among age classes in Cu, Zn, Hg, and Se concentrations. The highest concentrations of Se, Cd, Sn, Hg, and Pb were found in one adult female false killer whale (Pseudorca crassidens) at concentrations that are known to affect health in marine mammals. The results of this study establish initial trace element concentration ranges for Pacific cetaceans in the Hawaiian Islands region, provide insights into contaminant exposure of these marine mammals, and contribute to a greater understanding of anthropogenic impacts in the Pacific Ocean. PMID- 26283021 TI - RetFM-J, an ImageJ-based module for automated counting and quantifying features of nuclei in retinal whole-mounts. AB - The present article introduces RetFM-J, a semi-automated ImageJ-based module that detects, counts, and collects quantitative data on nuclei of the inner retina from H&E-stained whole-mounted retinas. To illustrate performance, computer derived outputs were analyzed in inbred C57BL/6J mice. Automated characterization yielded computer-derived outputs that closely matched manual counts. As a method using open-source software that is freely available, inexpensive staining reagents that are robust, and imaging equipment that is routine to most laboratories, RetFM-J could be utilized in a wide variety of experiments benefiting from high-throughput, quantitative, uniform analyses of total cellularity in the inner retina. PMID- 26283020 TI - MERTK signaling in the retinal pigment epithelium regulates the tyrosine phosphorylation of GDP dissociation inhibitor alpha from the GDI/CHM family of RAB GTPase effectors. AB - Photoreceptor outer segments (OS) in the vertebrate retina undergo a process of continual renewal involving shedding of disc membranes that are cleared by phagocytic uptake into the retinal pigment epithelium (RPE). In dystrophic Royal College of Surgeons (RCS) rats, OS phagocytosis is blocked by a mutation in the gene encoding the receptor tyrosine kinase MERTK. To identify proteins tyrosine phosphorylated downstream of MERTK in the RPE, MALDI-mass spectrometry with peptide-mass fingerprinting was used in comparative studies of RCS congenic and dystrophic rats. At times corresponding to peak phagocytic activity, the RAB GTPase effector GDP dissociation inhibitor alpha (GDI1) was found to undergo tyrosine phosphorylation only in congenic rats. In cryosections of native RPE/choroid, GDI1 colocalized with MERTK and the intracellular tyrosine-kinase SRC. In cultured RPE-J cells, and in transfected heterologous cells, MERTK stimulated SRC-mediated tyrosine phosphorylation of GDI1. In OS-fed RPE-J cells, GDI1 colocalized with MERTK and SRC on apparent phagosomes located near the apical membrane. In addition, both GDI1 and RAB5, a regulator of vesicular transport, colocalized with ingested OS. Taken together, these findings identify a novel role of MERTK signaling in membrane trafficking in the RPE that is likely to subserve mechanisms of phagosome formation. PMID- 26283022 TI - Whole-genome sequencing reveals the effect of vaccination on the evolution of Bordetella pertussis. AB - Herd immunity can potentially induce a change of circulating viruses. However, it remains largely unknown that how bacterial pathogens adapt to vaccination. In this study, Bordetella pertussis, the causative agent of whooping cough, was selected as an example to explore possible effect of vaccination on the bacterial pathogen. We sequenced and analysed the complete genomes of 40 B. pertussis strains from Finland and China, as well as 11 previously sequenced strains from the Netherlands, where different vaccination strategies have been used over the past 50 years. The results showed that the molecular clock moved at different rates in these countries and in distinct periods, which suggested that evolution of the B. pertussis population was closely associated with the country vaccination coverage. Comparative whole-genome analyses indicated that evolution in this human-restricted pathogen was mainly characterised by ongoing genetic shift and gene loss. Furthermore, 116 SNPs were specifically detected in currently circulating ptxP3-containing strains. The finding might explain the successful emergence of this lineage and its spread worldwide. Collectively, our results suggest that the immune pressure of vaccination is one major driving force for the evolution of B. pertussis, which facilitates further exploration of the pathogenicity of B. pertussis. PMID- 26283023 TI - 24-Month-Old Children With Larger Oral Vocabularies Display Greater Academic and Behavioral Functioning at Kindergarten Entry. AB - Data were analyzed from a population-based, longitudinal sample of 8,650 U.S. children to (a) identify factors associated with or predictive of oral vocabulary size at 24 months of age and (b) evaluate whether oral vocabulary size is uniquely predictive of academic and behavioral functioning at kindergarten entry. Children from higher socioeconomic status households, females, and those experiencing higher quality parenting had larger oral vocabularies. Children born with very low birth weight or from households where the mother had health problems had smaller oral vocabularies. Even after extensive covariate adjustment, 24-month-old children with larger oral vocabularies displayed greater reading and mathematics achievement, increased behavioral self-regulation, and fewer externalizing and internalizing problem behaviors at kindergarten entry. PMID- 26283024 TI - PDGFRbeta(+) cells in human and experimental neuro-vascular dysplasia and seizures. AB - INTRODUCTION: Neuro-vascular rearrangement occurs in brain disorders, including epilepsy. Platelet-derived growth factor receptor beta (PDGFRbeta) is used as a marker of perivascular pericytes. Whether PDGFRbeta(+) cell reorganization occurs in regions of neuro-vascular dysplasia associated with seizures is unknown. METHODS: We used brain specimens derived from epileptic subjects affected by intractable seizures associated with focal cortical dysplasia (FCD) or temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). Tissues from cryptogenic epilepsy, non-sclerotic hippocampi or peritumoral were used for comparison. An in vivo rat model of neuro-vascular dysplasia was obtained by pre-natal exposure to methyl-axozy methanoic acid (MAM). Status epilepticus (SE) was induced in adult MAM rats by intraperitoneal pilocarpine. MAM tissues were also used to establish organotypic hippocampal cultures (OHC) to further assess pericytes positioning at the dysplastic microvasculature. PDGFRbeta and its colocalization with RECA-1 or CD34 were used to segregate perivascular pericytes. PDGFRbeta and NG2 or IBA1 colocalization were performed. Rat cortices and hippocampi were used for PDGFRbeta western blot analysis. RESULTS: Human FCD displayed the highest perivascular PDGFRbeta immunoreactivity, indicating pericytes, and presence of ramified PDGFRbeta(+) cells in the parenchyma and proximal to microvessels. Tissues deriving from human cryptogenic epilepsy displayed a similar pattern of immunoreactivity, although to a lesser extent compared to FCD. In TLE-HS, CD34 vascular proliferation was paralleled by increased perivascular PDGFRbeta(+) pericytes, as compared to non-HS. Parenchymal PDGFRbeta immunoreactivity co localized with NG2 but was distinct from IBA1(+) microglia. In MAM rats, we found pericyte-vascular changes in regions characterized by neuronal heterotopias. PDGFRbeta immunoreactivity was differentially distributed in the heterotopic and adjacent normal CA1 region. The use of MAM OHC revealed microvascular-pericyte dysplasia at the capillary tree lining the dentate gyrus (DG) molecular layer as compared to control OHC. Severe SE induced PDGFRbeta(+) immunoreactivity mostly in the CA1 region of MAM rats. CONCLUSION: Our descriptive study points to microvascular-pericyte changes in the epileptic pathology. The possible link between PDGFRbeta(+) cells, neuro-vascular dysplasia and remodeling during seizures is discussed. PMID- 26283025 TI - Inhibitory actions of bisabolol on alpha7-nicotinic acetylcholine receptors. AB - Bisabolol is a plant-derived monocyclic sesquiterpene alcohol with antinociceptive and antiinflammatory actions. However, molecular targets mediating these effects of bisabolol are poorly understood. In this study, using a two-electrode voltage-clamp and patch-clamp techniques and live cellular calcium imaging, we have investigated the effect of bisabolol on the function of human alpha7 subunit of nicotinic acetylcholine receptor (nAChR) in Xenopus oocytes, interneurons of rat hippocampal slices. We have found that bisabolol reversibly and concentration dependently (IC50 = 3.1 MUM) inhibits acetylcholine (ACh)-induced alpha7 receptor-mediated currents. The effect of bisabolol was not dependent on the membrane potential. Bisabolol inhibition was not changed by intracellular injection of the Ca(2+) chelator BAPTA and perfusion with Ca(2+) free solution containing Ba(2+), suggesting that endogenous Ca(2+)-dependent Cl( ) channels are not involved in bisabolol actions. Increasing the concentrations of ACh did not reverse bisabolol inhibition. Furthermore, the specific binding of [(125)I] alpha-bungarotoxin was not attenuated by bisabolol. Choline-induced currents in CA1 interneurons of rat hippocampal slices were also inhibited with IC50 of 4.6 MUM. Collectively, our results suggest that bisabolol directly inhibits alpha7-nAChRs via a binding site on the receptor channel. PMID- 26283026 TI - The effects of entrance pupil centration and coma aberrations on myopic progression following orthokeratology. AB - BACKGROUND: The aim was to assess the potential association between entrance pupil location relative to the coaxially sighted corneal light reflex (CSCLR) and the progression of myopia in children fitted with orthokeratology (OK) contact lenses. Additionally, whether coma aberration induced by decentration of the entrance pupil centre relative to the CSCLR, as well as following OK treatment, is correlated with the progression of myopia, was also investigated. METHODS: Twenty-nine subjects aged six to 12 years and with myopia of -0.75 to -4.00 DS and astigmatism up to 1.00 DC were fitted with OK contact lenses. Measurements of axial length and corneal topography were taken at six-month intervals over a two year period. Additionally, baseline and three-month topographic outputs were taken as representative of the pre- and post-orthokeratology treatment status. Pupil centration relative to the CSCLR and magnitude of associated corneal coma were derived from corneal topographic data at baseline and after three months of lens wear. RESULTS: The centre of the entrance pupil was located superio temporally to the CSCLR both pre- (0.09 +/- 0.14 and -0.10 +/- 0.15 mm, respectively) and post-orthokeratology (0.12 +/- 0.18 and -0.09 +/- 0.15 mm, respectively) (p > 0.05). Entrance pupil location pre- and post-orthokeratology lens wear was not significantly associated with the two-year change in axial length (p > 0.05). Significantly greater coma was found at the entrance pupil centre compared with CSCLR both pre- and post-orthokeratology lens wear (both p < 0.05). A significant increase in vertical coma was found with OK lens wear compared to baseline (p < 0.001) but total root mean square (RMS) coma was not associated with the change in axial length (all p > 0.05). CONCLUSION: Entrance pupil location relative to the CSCLR was not significantly affected by either OK lens wear or an increase in axial length. Greater magnitude coma aberrations found at the entrance pupil centre in comparison to the CSCLR might be attributed to centration of orthokeratological treatments at the CSCLR. PMID- 26283028 TI - Response to the Letter Entitled "Comments Concerning Comparison of Airway and Systemic Malondialdehyde Levels for Assessment of Oxidative Stress in Cystic Fibrosis". PMID- 26283027 TI - Association analysis identifies new risk loci for congenital heart disease in Chinese populations. AB - Our previous genome-wide association study (GWAS) identified two susceptibility loci for congenital heart disease (CHD) in Han Chinese. Here we identify additional loci by testing promising associations in an extended 3-stage validation consisting of 6,053 CHD cases and 7,410 controls. We find GW significant (P<5.0 * 10(-8)) evidence of 4 additional CHD susceptibility loci at 4q31.22 (rs1400558, upstream of EDNRA, Pall=1.63 * 10(-9)), 9p24.2 (rs7863990, close to SMARCA2, Pall=3.71 * 10(-14)), 12q24.13 (rs2433752, upstream of TBX3 and TBX5, Pall=1.04 * 10(-10)) and 20q12 (rs490514, in PTPRT, Pall=1.20 * 10(-13)). Moreover, the data from previous European GWAS supports that rs490514 is associated with the risk of CHD (P=3.40 * 10(-3)). These results enhance our understanding of CHD susceptibility. PMID- 26283029 TI - Retraction Note to: Protein-Protein Interaction Network Analysis in Chronic Obstructive Pulmonary Disease. PMID- 26283030 TI - Retraction Note to: ATF3 and Extracellular Matrix-Related Genes Associated with the Process of Chronic Obstructive Pulmonary. PMID- 26283031 TI - Retraction Note to: The Influence of mtDNA Deletion on Lung Cancer Cells Under the Conditions of Hypoxia and Irradiation. PMID- 26283032 TI - Annual trend patterns of phytoplankton species abundance belie homogeneous taxonomical group responses to climate in the NE Atlantic upwelling. AB - Phytoplankton is a sentinel of marine ecosystem change. Composed by many species with different life-history strategies, it rapidly responds to environment changes. An analysis of the abundance of 54 phytoplankton species in Galicia (NW Spain) between 1989 and 2008 to determine the main components of temporal variability in relation to climate and upwelling showed that most of this variability was stochastic, as seasonality and long term trends contributed to relatively small fractions of the series. In general, trends appeared as non linear, and species clustered in 4 groups according to the trend pattern but there was no defined pattern for diatoms, dinoflagellates or other groups. While, in general, total abundance increased, no clear trend was found for 23 species, 14 species decreased, 4 species increased during the early 1990s, and only 13 species showed a general increase through the series. In contrast, series of local environmental conditions (temperature, stratification, nutrients) and climate-related variables (atmospheric pressure indices, upwelling winds) showed a high fraction of their variability in deterministic seasonality and trends. As a result, each species responded independently to environmental and climate variability, measured by generalized additive models. Most species showed a positive relationship with nutrient concentrations but only a few showed a direct relationship with stratification and upwelling. Climate variables had only measurable effects on some species but no common response emerged. Because its adaptation to frequent disturbances, phytoplankton communities in upwelling ecosystems appear less sensitive to changes in regional climate than other communities characterized by short and well defined productive periods. PMID- 26283033 TI - Too Much Information may not always be a Good Thing. PMID- 26283034 TI - Dual Antiplatelet Therapy Prior to Expedited Carotid Surgery Reduces Recurrent Events Prior to Surgery without Significantly Increasing Peri-operative Bleeding Complications. AB - OBJECTIVE: A daily Rapid-Access TIA Clinic was introduced in 2008, where symptomatic patients were started on 75 mg aspirin + 40 mg simvastatin by the referring doctor, before attending the clinic. Following clinic assessment, patients with 50-99% stenoses were transferred to the vascular unit for carotid endarterectomy (CEA). In two audits (n = 212 patients), the median delay from transfer to the vascular unit to undergoing CEA was 3 days, during which time 28 patients (13%) suffered recurrent neurological events. It was hypothesized that early introduction of dual antiplatelet therapy (by adding clopidogrel 75 mg once parenchymal haemorrhage was excluded in the TIA clinic) might significantly reduce recurrent events between transfer to the surgical unit and undergoing CEA. METHODS: Prospective audit in 100 consecutive, recently symptomatic patients receiving dual antiplatelet therapy. Endpoints were: prevalence of recurrent events between transfer from the TIA clinic and undergoing CEA; rates of spontaneous embolization prior to undergoing CEA; and prevalence of haemorrhagic complications RESULTS: The median delay from symptom to CEA was 8 days (IQR 5 15). The median delay between transfer from the TIA clinic to CEA was 3 days (IQR 2-5), during which time three patients (3%) suffered recurrent TIAs. This represents a fivefold reduction compared with previous audit data (OR 4.9, 95% CI 1.5-16.6, p = .01) and was matched by a fourfold reduction in the prevalence of spontaneous embolization from 39/189 (21%) previously to 5/83 (5%) in the current audit (OR 4.1, 95% CI 1.5-10.7, p = .0047). The 30-day death/stroke rate was 1%. There were three haemorrhagic complications: stroke caused by haemorrhagic transformation of an infarct; exploration for neck haematoma; and debridement and skin grafting for spontaneous shin haematoma. CONCLUSION: Early introduction of dual antiplatelet therapy was associated with a significant reduction in recurrent neurological events and spontaneous embolization prior to CEA, without incurring a significant increase in major peri-operative bleeding complications. PMID- 26283035 TI - A phase III study of belagenpumatucel-L, an allogeneic tumour cell vaccine, as maintenance therapy for non-small cell lung cancer. AB - BACKGROUND: Treatment options after first-line chemotherapy are limited in non small cell lung cancer (NSCLC). Belagenpumatucel-L is a therapeutic vaccine comprised of 4 transforming growth factor (TGF)-beta2-antisense gene-modified, irradiated, allogeneic NSCLC cell lines that may be useful for maintenance after initial treatment. METHODS: Stage III/IV NSCLC patients who did not progress after platinum-based chemotherapy were randomised 1:1 to receive maintenance belagenpumatucel-L or placebo. Patients were eligible for randomisation between one and four months from the end of induction chemotherapy. The primary endpoint was overall survival. RESULTS: This phase III trial enrolled 270 patients in the belagenpumatucel-L arm and 262 in the control arm. Belagenpumatucel-L was well tolerated with no serious safety concerns. There was no difference in survival between the arms (median survival 20.3 versus 17.8months with belagenpumatucel-L versus placebo, respectively; hazard ratio (HR) 0.94, p=0.594). There were also no differences in progression-free survival (4.3months versus 4.0 for belagenpumatucel-L vs placebo, respectively; HR 0.99, p=0.947). A prespecified Cox regression analysis demonstrated that the time elapsed between randomisation and the end of induction chemotherapy had a significant impact on survival (p=0.002) and that prior radiation was a positive prognostic factor (median survival 28.4months with belagenpumatucel-L versus 16.0months with placebo; HR 0.61, p=0.032). CONCLUSIONS: Although the overall trial did not meet its survival endpoint, improved survival for belagenpumatucel-L is suggested in patients who were randomised within 12weeks of completion of chemotherapy and in those who had received prior radiation. Further studies of belagenpumatucel-L in NSCLC are warranted. PMID- 26283036 TI - Imatinib in advanced chordoma: A retrospective case series analysis. AB - INTRODUCTION: Imatinib showed activity in 50 chordoma patients treated within a Phase II study. In that study, 70% of patients remained with stable disease (SD), median progression free survival (PFS) was 9 months and median overall survival (OS) was 34 months. We now report on a retrospective series of PDGFB/PDGFRB positive advanced chordoma patients treated with imatinib as a single agent within a compassionate-use programme at Istituto Nazionale Tumori, Milan, Italy (INT) between August 2002 and November 2010, when the programme was closed. METHODS: 48 patients were consecutively treated with imatinib 800 mg/d. All patients had inoperable and progressive disease before starting imatinib. Demographics, treatment duration, toxicity and response rate by Response Evaluation Criteria in Solid Tumors (RECIST) were retrospectively recorded. RESULTS: The median duration of therapy was 7 months (1-46.5). No patient is on therapy at present. 46 patients were evaluable for response. No partial responses were detected. Best response was: stable disease 34 (74%), progressive disease 12 (26%). At a median follow-up of 24.5 months (0.5-117), median PFS was 9.9 months (95% confidence interval (CI) 6.7-13). Eight patients (16.5%) remained on therapy >18 months and 10 patients (21%) remained progression-free >18 months. Median OS was 30 months (95% CI 20-40), with 24 (50%) patients dead at the time of the present analysis. CONCLUSIONS: We confirm the activity of imatinib in locally advanced and metastatic chordoma, in terms of >70% tumour growth arrest in previously progressive patients. Median duration of response lasted almost 10 months, with >20% of patients progression-free at 18+ months. PMID- 26283037 TI - Optimal breast cancer pathology manifesto. AB - This manifesto was prepared by a European Breast Cancer (EBC) Council working group and launched at the European Breast Cancer Conference in Glasgow on 20 March 2014. It sets out optimal technical and organisational requirements for a breast cancer pathology service, in the light of concerns about variability and lack of patient-centred focus. It is not a guideline about how pathology services should be performed. It is a call for all in the cancer community--pathologists, oncologists, patient advocates, health administrators and policymakers--to check that services are available that serve the needs of patients in a high quality, timely way. PMID- 26283038 TI - Adolescent and parental perceptions about asthma and asthma management: a dyadic qualitative analysis. AB - BACKGROUND: Considering that asthma management is a family affair - with specific challenges in adolescence - a better understanding of both adolescent and parental perspectives on asthma and its treatment are needed as these constructs may substantially account for variation in illness-related behaviour and functioning. The present study aimed to (1) explore adolescents' and caregivers' perceptions about asthma and asthma management and (2) examine congruence and dissimilarities within the adolescent-caregiver dyads. METHODS: Data collection was conducted separately for adolescents and caregivers using a focus group approach for the adolescents and telephone interviews for parental data collection. In total, dyadic data from n = 15 adolescent patients with asthma (aged 11-17 years, M = 14.9) and their mothers (aged 37-55 years, M = 46.3) were considered in the study. The interviews were transcribed verbatim and analysed in a dyad-focused multistep qualitative content analysis procedure using the software. RESULTS: The results demonstrated high complexity in the perceptions among adolescents and mothers and reflected 113 specific themes that could be assigned to four main topics: asthma beliefs, representations of asthma treatment, perceptions about individual asthma management and perceptions about family asthma management. Dyadic analyses revealed congruence in the adolescent caregiver dyads in most of the themes. However, we also found issues where divergent perceptions became evident including, for example, perceptions of asthma's general impact on adolescents' life or the question of who takes the main responsibility in asthma management. CONCLUSIONS: Adolescents' and caregivers' perceptions were found to reflect a great variety of beliefs regarding the adolescents' illness and illness-related behaviour on both the individual and the family level. The study adds to the illness perceptions literature by providing a systemic perspective that was rather rarely presented in prior research. PMID- 26283040 TI - Genetic predisposition to higher blood pressure increases risk of incident hypertension and cardiovascular diseases in Chinese. AB - Although multiple genetic markers associated with blood pressure have been identified by genome-wide association studies, their aggregate effect on risk of incident hypertension and cardiovascular disease is uncertain, particularly among East Asian who may have different genetic and environmental exposures from Europeans. We aimed to examine the association between genetic predisposition to higher blood pressure and risk of incident hypertension and cardiovascular disease in 26 262 individuals in 2 Chinese population-based prospective cohorts. A genetic risk score was calculated based on 22 established variants for blood pressure in East Asian. We found the genetic risk score was significantly and independently associated with linear increases in blood pressure and risk of incident hypertension and cardiovascular disease (P range from 4.57*10(-3) to 3.10*10(-6)). In analyses adjusted for traditional risk factors including blood pressure, individuals carrying most blood pressure-related risk alleles (top quintile of genetic score distribution) had 40% (95% confidence interval, 18-66) and 26% (6-45) increased risk for incident hypertension and cardiovascular disease, respectively, when compared with individuals in the bottom quintile. The genetic risk score also significantly improved discrimination for incident hypertension and cardiovascular disease and led to modest improvements in risk reclassification for cardiovascular disease (all the P<0.05). Our data indicate that genetic predisposition to higher blood pressure is an independent risk factor for blood pressure increase and incident hypertension and cardiovascular disease and provides modest incremental information to cardiovascular disease risk prediction. The potential clinical use of this panel of blood pressure associated polymorphisms remains to be determined. PMID- 26283041 TI - Altered retinal flicker response indicates microvascular dysfunction in women with preeclampsia. AB - Flicker-induced dilatation is reduced in patients with cardiovascular risk, and the following arteriolar constriction is reduced with aging, leading to a reduced arteriolar amplitude and, thereby, indicating microvascular endothelial dysfunction. As endothelial dysfunction is associated with preeclampsia, we assessed retinal flicker response during pregnancy and postpartum. Between 2006 and 2013, women were recruited from University Hospital Jena and Prenatal Diagnostic Center Erfurt, Germany, of which 34 women with preeclampsia, 45 women with normal pregnancy, and 22 nonpregnant controls were included in the study. Women with normal pregnancy were matched for age, nulliparity, smoking, previous gestational hypertensive disorders, and family history of cardiovascular disease. Nonpregnant women were age-matched, nulliparous, nonsmoking, without family history of cardiovascular disease. Retinal vessel measurement using Dynamic Vessel Analyzer consisted of 50-seconds baseline acquisition, followed by three 20-second flicker and 80-second relaxation periods. Arteriolar constriction and arteriolar amplitude were reduced during pregnancy (P=0.001 and P=0.008) and postpartum (P=0.018 and P=0.034) in women with preeclampsia, adjusted for age, body mass index, mean arterial pressure, baseline diameter, and family history of cardiovascular disease. Flicker-induced dilatation was unchanged within the groups and throughout the study period. The unchanged flicker-induced dilatation may support a preserved autoregulatory competence of the microvasculature, and the diminished arteriolar amplitude, mainly because of the absence of the arteriolar constriction, indicates a commenced retinal microvascular dysfunction in women with preeclampsia during pregnancy and postpartum. Mechanisms responsible for altered retinal flicker response in preeclampsia need to be clarified in further studies. PMID- 26283039 TI - Rho-associated kinase activity is an independent predictor of cardiovascular events in acute coronary syndrome. AB - Rho-associated kinases play an important role in a variety of cellular functions. Although Rho-associated kinase activity has been shown to be an independent predictor for future cardiovascular events in a general population, there is no information on Rho-associated kinase activity in patients with acute coronary syndrome. We evaluated leukocyte Rho-associated kinase activity by Western blot analysis in 73 patients with acute coronary syndrome and 73 age- and gender matched control subjects. Rho-associated kinase activity within 2 hours of acute coronary syndrome onset was higher in patients with acute coronary syndrome than in the control subjects (0.95+/-0.55 versus 0.69+/-0.31; P<0.001). Rho-associated kinase activity promptly increased from 0.95+/-0.55 to 1.11+/-0.81 after 3 hours and reached a peak of 1.21+/-0.76 after 1 day (P=0.03 and P=0.03, respectively) and then gradually decreased to 0.83+/-0.52 after 7 days, 0.78+/-0.42 after 14 days, and 0.72+/-0.30 after 6 months (P=0.22, P=0.29, and P=0.12, respectively). During a median follow-up period of 50.8 months, 31 first major cardiovascular events (death from cardiovascular causes, myocardial infarction, ischemic stroke, and coronary revascularization) occurred. After adjustment for age, sex, cardiovascular risk factors, and concomitant treatment with statins, increased Rho-associated kinase activity was associated with increasing risk of first major cardiovascular events (hazard ratio, 4.56; 95% confidence interval, 1.98-11.34; P<0.001). These findings suggest that Rho-associated kinase activity is dramatically changed after acute coronary syndrome and that Rho-associated kinase activity could be a useful biomarker to predict cardiovascular events in Japanese patients with acute coronary syndrome. PMID- 26283044 TI - [32nd Congress of French Society of Endocrinology in Angers on October 7-10, 2015]. PMID- 26283043 TI - Endogenous microRNAs in human microvascular endothelial cells regulate mRNAs encoded by hypertension-related genes. AB - The goal of this study was to systematically identify endogenous microRNAs (miRNAs) in endothelial cells that regulate mRNAs encoded by genes relevant to hypertension. Small RNA deep sequencing was performed in cultured human microvascular endothelial cells. Of the 50 most abundant miRNAs identified, 30 had predicted target mRNAs encoded by genes with known involvement in hypertension or blood pressure regulation. The cells were transfected with anti miR oligonucleotides to inhibit each of the 30 miRNAs and the mRNA abundance of predicted targets was examined. Of 95 miRNA-target pairs examined, the target mRNAs were significantly upregulated in 35 pairs and paradoxically downregulated in 8 pairs. The result indicated significant suppression of the abundance of mRNA encoded by ADM by endogenous miR-181a-5p, ATP2B1 by the miR-27 family, FURIN by miR-125a-5p, FGF5 by the let-7 family, GOSR2 by miR-27a-3p, JAG1 by miR-21-5p, SH2B3 by miR-30a-5p, miR-98, miR-181a-5p, and the miR-125 family, TBX3 by the miR 92 family, ADRA1B by miR-22-3p, ADRA2A by miR-30a-5p and miR-30e-5p, ADRA2B by miR-30e-5p, ADRB1 by the let-7 family and miR-98, EDNRB by the miR-92 family, and NOX4 by the miR-92 family, miR-100-5p, and miR-99b-5p (n=3-9; P<0.05 versus scrambled anti-miR). Treatment with anti-miR-21 decreased blood pressure in mice fed a 4% NaCl diet. Inhibition of the miRNAs targeting NOX4 mRNA increased H2O2 release from endothelial cells. The findings indicate widespread, tonic control of mRNAs encoded by genes relevant to blood pressure regulation by endothelial miRNAs and provide a novel and uniquely informative basis for studying the role of miRNAs in hypertension. PMID- 26283042 TI - Clinical effects of phosphodiesterase 3A mutations in inherited hypertension with brachydactyly. AB - Autosomal-dominant hypertension with brachydactyly is a salt-independent Mendelian syndrome caused by activating mutations in the gene encoding phosphodiesterase 3A. These mutations increase the protein kinase A-mediated phosphorylation of phosphodiesterase 3A resulting in enhanced cAMP-hydrolytic affinity and accelerated cell proliferation. The phosphorylated vasodilator stimulated phosphoprotein is diminished, and parathyroid hormone-related peptide is dysregulated, potentially accounting for all phenotypic features. Untreated patients die prematurely of stroke; however, hypertension-induced target-organ damage is otherwise hardly apparent. We conducted clinical studies of vascular function, cardiac functional imaging, platelet function in affected and nonaffected persons, and cell-based assays. Large-vessel and cardiac functions indeed seem to be preserved. The platelet studies showed normal platelet function. Cell-based studies demonstrated that available phosphodiesterase 3A inhibitors suppress the mutant isoforms. However, increasing cGMP to indirectly inhibit the enzyme seemed to have particular use. Our results shed more light on phosphodiesterase 3A activation and could be relevant to the treatment of severe hypertension in the general population. PMID- 26283045 TI - Harnessing microbial gene pools to remediate persistent organic pollutants using genetically modified plants--a viable technology? AB - It has been 14 years since the international community came together to legislate the Stockholm Convention on Persistent Organic Pollutants (POPs), restricting the production and use of specific chemicals that were found to be environmentally stable, often bioaccumulating, with long-term toxic effects. Efforts are continuing to remove these pollutants from the environment. While incineration and chemical treatment can be successful, these methods require the removal of tonnes of soil, at high cost, and are damaging to soil structure and microbial communities. The engineering of plants for in situ POP remediation has had highly promising results, and could be a more environmentally-friendly alternative. This review discusses the characterization of POP-degrading bacterial pathways, and how the genes responsible have been harnessed using genetic modification (GM) to introduce these same abilities into plants. Recent advances in multi-gene cloning, genome editing technologies and expression in monocot species are accelerating progress with remediation-applicable species. Examples include plants developed to degrade 2,4,6-trinitrotoluene (TNT), hexahydro-1,3,5-trinitro 1,3,5-triazine (RDX), trichloroethylene (TCE), and polychlorinated biphenyls (PCBs). However, the costs and timescales needed to gain regulatory approval, along with continued public opposition, are considerable. The benefits and challenges in this rapidly developing and promising field are discussed. PMID- 26283046 TI - Polypyrimidine tract-binding proteins of potato mediate tuberization through an interaction with StBEL5 RNA. AB - Polypyrimidine tract-binding (PTB) proteins are a family of RNA-binding proteins that function in a wide range of RNA metabolic processes by binding to motifs rich in uracils and cytosines. A PTB protein of pumpkin was identified as the core protein of an RNA-protein complex that trafficks RNA. The biological function of the PTB-RNA complex, however, has not been demonstrated. In potato, six PTB proteins have been identified, and two, designated StPTB1 and StPTB6, are similar to the phloem-mobile pumpkin type. RNA binding assays confirmed the interaction of StPTB1 and StPTB6 with discrete pyrimidine-rich sequences of the 3'-untranslated regions of the phloem-mobile mRNA, StBEL5. The promoter of StPTB1 was active in companion cells of phloem in both stem and petioles. Expression of both types was evident in phloem cells of roots and in stolons during tuber formation. RNA accumulation of both PTB proteins was induced by short days in leaves in correlation with enhanced accumulation of StBEL5 RNA. StPTB suppression lines exhibited reduced tuber yields and decreased StBEL5 RNA accumulation, whereas StPTB overexpression lines displayed an increase in tuber production correlated with the enhanced production in stolons of steady-state levels of StBEL5 transcripts and RNA of key tuber identity genes. In StPTB overexpression lines, both the stability and long-distance transport of StBEL5 transcripts were enhanced, whereas in suppression lines stability and transport decreased. Using a transgenic approach, it is shown that the StPTB family of RNA-binding proteins regulate specific stages of development through an interaction with phloem-mobile transcripts of StBEL5. PMID- 26283047 TI - An-2 Encodes a Cytokinin Synthesis Enzyme that Regulates Awn Length and Grain Production in Rice. AB - A wide range of morphological and physiological traits have changed between cultivated rice Oryza sativa and wild rice Oryza rufipogon under domestication. Here, we report cloning of the An-2 gene, encoding the Lonely Guy Like protein 6 (OsLOGL6), which catalyzes the final step of cytokinin synthesis in O. rufipogon. The near-isogenic line harboring a wild allele of An-2 in the genetic background of the awnless indica Guangluai 4 shows that An-2 promotes awn elongation by enhancing cell division, but decreases grain production by reducing grains per panicle and tillers per plant. We reveal that a genetic variation in the An-2 locus has a large impact on reducing awn length and increasing tiller and grain numbers in domesticated rice. Analysis of gene expression patterns suggests that An-1 regulates the formation of awn primordial, and An-2 promotes awn elongation. Nucleotide diversity of the An-2 locus in cultivated rice was found to be significantly reduced compared with that of wild rice, suggesting that the An-2 locus was subjected to artificial selection. We therefore propose that the selection of genetic variation in An-2 was due to reduced awn length and increased grain yield in cultivated rice. PMID- 26283048 TI - Identification of AtOPT4 as a Plant Glutathione Transporter. PMID- 26283049 TI - In Vitro Comparison of Active and Passive Physiological Control Systems for Biventricular Assist Devices. AB - The low preload and high afterload sensitivities of rotary ventricular assist devices (VADs) may cause ventricular suction events or venous congestion. This is particularly problematic with rotary biventricular support (BiVAD), where the Starling response is diminished in both ventricles. Therefore, VADs may benefit from physiological control systems to prevent adverse events. This study compares active, passive and combined physiological controllers for rotary BiVAD support with constant speed mode. Systemic (SVR) and pulmonary (PVR) vascular resistance changes and exercise were simulated in a mock circulation loop to evaluate the capacity of each controller to prevent suction and congestion and increase exercise capacity. All controllers prevented suction and congestion at high levels of PVR (900 dynes s cm(-5)) and SVR (3000 dynes s cm(-5)), however these events occurred in constant speed mode. The controllers increased preload sensitivity (0.198-0.34 L min(-1) mmHg(-1)) and reduced afterload sensitivity (0.0001-0.008 L min(-1) mmHg(-1)) of the VADs when compared to constant speed mode (0.091 and 0.072 L min(-1) mmHg(-1) respectively). The active controller increased pump speeds (400-800 rpm) and pump flow by 2.8 L min(-1) during exercise, thus increasing exercise capacity. By reducing suction and congestion and by increasing exercise capacity, the control systems presented in this study may help increase quality of life of VAD patients. PMID- 26283051 TI - Rapid RBE-Weighted Proton Radiation Dosimetry Risk Assessment. AB - Proton therapy dose is affected by relative biological effectiveness differently than X-ray therapies. The current clinically accepted weighting factor is 1.1 at all positions along the depth-dose profile. However, the relative biological effectiveness correlates with the linear energy transfer, cell or tissue type, and the dose per fraction causing variation of relative biological effectiveness along the depth-dose profile. In this article, we present a simple relative biological effectiveness-weighted treatment planning risk assessment algorithm in 2-dimensions and compare the results with those derived using the standard relative biological effectiveness of 1.1. The isodose distribution profiles for beams were accomplished using matrices that represent coplanar intersecting beams. These matrices were combined and contoured using MATLAB to achieve the distribution of dose. There are some important differences in dose distribution between the dose profiles resulting from the use of relative biological effectiveness = 1.1 and the empirically derived depth-dependent values of relative biological effectiveness. Significant hot spots of up to twice the intended dose are indicated in some beam configurations. This simple and rapid risk analysis could quickly evaluate the safety of various dose delivery schema. PMID- 26283050 TI - MiR-138 inhibits cell proliferation and reverses epithelial-mesenchymal transition in non-small cell lung cancer cells by targeting GIT1 and SEMA4C. AB - Non-small-cell lung cancer (NSCLC) is one of the most common and lethal malignant tumours worldwide with a poor 5-year survival rate. Recent studies indicated that miRNAs have been involved in the tumorigenic driver pathways in NSCLC, but the relevant molecular mechanisms are not well-understood. In this study, we investigated the biological functions and molecular mechanisms of miR-138 in human NSCLC. The effects of miR-138 on the NSCLC cell growth and epithelial mesenchymal transition (EMT) were first examined. Then the targeting connections of miR-138 with G-protein-coupled receptor kinase-interacting protein 1 (GIT1) and semaphorin 4C (SEMA4C) were confirmed by dual luciferase reporter assays. Finally, the effects of GIT1 and SEMA4C on the NSCLC cell growth and EMT were investigated respectively. We found that the ectopic expression of miR-138 resulted in a significant inhibition of NSCLC growth and reversion of EMT. GIT1 and SEMA4C were identified as two novel targets of miR-138. Furthermore, GIT1 and SEMA4C knockdown inhibited the cell growth and reversed EMT, just like the effects of miR-138 overexpression on NSCLC cells, whereas ectopic expression of GIT1 and SEMA4C partly rescued the suppressive effects of miR-138 in NSCLC cells. These data represent a crucial step towards the understanding of the novel roles and molecular mechanism of miR-138, GIT1 and SEMA4C in NSCLC progression, which may provide some new targets or prognostic biomarkers for NSCLC treatment, thus having implications in translational oncology. PMID- 26283052 TI - Association Between the CYP1B1 Polymorphisms and Lung Cancer Risk: A Meta Analysis. AB - The previously published data on the association between the cytochrome P450 1B1 Leu432Val, Asn453Ser, and Ala119Ser polymorphisms and lung cancer risk have remained controversial. Hence, we performed a meta-analysis to investigate the association between cytochrome P450 1B1 Leu432Val, Asn453Ser, and Ala119Ser polymorphisms and lung cancer risk under different inheritance models. A total of 22 studies were identified, including 2881 cases and 3653 controls for Leu432Val polymorphism (from 13 studies), 3009 cases and 3887 controls for Asn453Ser polymorphism (from 5 studies), and 1301 cases and 2045 controls for Ala119Ser polymorphism (from 4 studies). Overall, significant association was observed between cytochrome P450 1B1 Leu432Val polymorphism and lung cancer risk (dominant model: odds ratio = 1.29, 95% confidence interval = 1.08-1.53; recessive model: odds ratio = 1.21, 95% confidence interval = 1.05-1.39; additive model: odds ratio = 1.43, 95% confidence interval = 1.21-1.69) when all the eligible studies were pooled into the meta-analysis. In the further stratified and sensitivity analyses, significantly increased lung cancer risk was also observed in caucasians and smokers. No significant association was observed between cytochrome P450 1B1Asn453Ser and Ala119Ser polymorphisms and lung cancer risk in overall analysis. In summary, this meta-analysis suggests that cytochrome P450 1B1Leu432Val polymorphism is associated with increased lung cancer risk in caucasians and smokers. PMID- 26283053 TI - Evaluating postoperative rotator cuff healing: Prospective comparison of MRI and ultrasound. AB - BACKGROUND: The objective of this prospective comparative single centre study was to compare postoperative rotator cuff healing rates as assessed by magnetic resonance imaging (MRI) versus ultrasonography (US). MATERIAL AND METHODS: Between October 2012 and February 2013, 61 patients underwent arthroscopic repair of postero-superior rotator cuff tears. Each patient underwent MRI and US 6 months later. The findings were assessed independently by two observers. We compared intra-observer and inter-observer levels of agreement regarding healing rates assessed by MRI and US. RESULTS: Intra-observer agreement regarding the MRI interpretation was 95% (kappa coefficient, 0.83) for one observer and 98% (kappa coefficient, 0.94) for the other. Values of kappa for inter-observer agreement ranged across readings from 0.76 to 0.90. When MRI was taken as the reference, US had 80% sensitivity and 98% specificity. DISCUSSION: MRI and US provide similar assessments of postoperative rotator cuff healing, although US is less sensitive. Intra-observer and inter-observer agreements are very good. PMID- 26283054 TI - Measuring fish body condition with or without parasites: does it matter? AB - A fish body condition index was calculated twice for each individual fish, including or excluding parasite mass from fish body mass, and index values were compared to test the effects of parasite mass on measurement of body condition. Potential correlations between parasite load and the two alternative fish condition index values were tested to assess how parasite mass may influence the perception of the actual effects of parasitism on fish body condition. Helminth parasite mass was estimated in common bully Gobiomorphus cotidianus from four New Zealand lakes and used to assess the biasing effects of parasite mass on body condition indices. Results showed that the inclusion or exclusion of parasite mass from fish body mass in index calculations significantly influenced correlation patterns between parasite load and fish body condition indices. When parasite mass was included, there was a positive correlation between parasite load and fish body condition, seemingly indicating that fish in better condition supported higher parasite loads. When parasite mass was excluded, there was no correlation between parasite load and fish body condition, i.e. there was no detectable effect of helminth parasites on fish condition or fish condition on parasite load. Fish body condition tended to be overestimated when parasite mass was not accounted for; results showed a positive correlation between relative parasite mass and the degree to which individual fish condition was overestimated. Regardless of the actual effects of helminth parasites on fish condition, parasite mass contained within a fish should be taken into account when estimating fish condition. Parasite tissues are not host tissues and should not be included in fish mass when calculating a body condition index, especially when looking at potential effects of helminth infections on fish condition. PMID- 26283055 TI - Making a Difference in Family Nursing: History of the Journal of Family Nursing Awards (2005-2011). PMID- 26283056 TI - Transition Needs of Parents of Adolescents and Emerging Adults With Special Health Care Needs and Disabilities. AB - The period of health care transition (HCT) for adolescents and emerging adults with special health care needs and disabilities involves a complex realignment of the parent-child relationship, including alterations in role responsibilities and decision making. The purpose of this systematic review was to analyze the research designs, methodology, and findings reported in studies of parents during this transition period to provide new insights for research and clinical practice. Results showed that parents were unable to clearly envision what the future held for their children and were not well prepared by the service system to anticipate future prospects. These parents have a myriad of needs that are not yet fully understood, as HCT research is in the early stages of development. PMID- 26283057 TI - Dr. Kristofer Arestedt Joins Journal of Family Nursing Editorial Board. PMID- 26283059 TI - Models for managing wildlife disease. AB - Modelling wildlife disease poses some unique challenges. Wildlife disease systems are data poor in comparison with human or livestock disease systems, and the impact of disease on population size is often the key question of interest. This review concentrates specifically on the application of dynamic models to evaluate and guide management strategies. Models have proved useful particularly in two areas. They have been widely used to evaluate vaccination strategies, both for protecting endangered species and for preventing spillover from wildlife to humans or livestock. They have also been extensively used to evaluate culling strategies, again both for diseases in species of conservation interest and to prevent spillover. In addition, models are important to evaluate the potential of parasites and pathogens as biological control agents. The review concludes by identifying some key research gaps, which are further development of models of macroparasites, deciding on appropriate levels of complexity, modelling genetic management and connecting models to data. PMID- 26283061 TI - Immobilisation of a molecular epoxidation catalyst on UiO-66 and -67: the effect of pore size on catalyst activity and recycling. AB - Amino-functionalised metal-organic frameworks UiO-66 and -67 were post synthetically modified with salicylaldehyde. A molybdenum complex was immobilised on the resulting materials. They were characterised by (13)C-MAS-NMR, XPS and PXRD to confirm immobilisation and stability. The immobilised complex is an active and reusable catalyst for olefin epoxidation with tert-butyl hydroperoxide (TBHP) as an oxidant. It is shown that the effective pore size, probed with Brunauer-Emmett-Teller (BET) surface area analysis and the number of amino groups affect the diffusion of reactants and products, as well as catalyst recycling. PMID- 26283060 TI - [Management of pulmonary embolism: A 2015 update]. AB - Pulmonary embolism (PE) is a frequent, serious and multifactorial disease, the incidence of which increases with advanced age. In the absence of pathognomonic clinical signs or symptoms, diagnostic management lies in the evaluation of clinical pre-test probability followed by a laboratory or an imaging test. So far, multidetector computed tomography angiography is the diagnostic test of choice to make a positive diagnosis of PE. Anticoagulants at therapeutic dose for at least 3 months constitute the cornerstones of PE therapeutic management. Duration of anticoagulant treatment is modulated according to the presence of transient (surgery, plaster immobilization, bed rest/hospitalization) and chronic/persistent (age, cancer, clinical or biological thrombophilia...) risk factors of PE. Thrombolysis is usually prescribed only for cases of severe PE with arterial hypotension. Arrival of new oral anticoagulants, which have recently been shown to be as effective and as safe as vitamin K antagonist, should simplify and ease ambulatory management of PE and favor more prolonged treatments with anticoagulant for cases of unprovoked PE or PE provoked by a chronic/persistent risk factor. PMID- 26283062 TI - Clinical and Counseling Experiences of Early Adopters of Whole Exome Sequencing. AB - Currently, there are limited data regarding the practice of genetic counseling for whole exome sequencing (WES). Improved understanding of how genetic counselors and other providers are educating, counseling, and communicating results may identify practice trends, and patient or provider needs. Between April 2013 and December 2014, we surveyed providers who ordered WES testing from GeneDx, a CLIA-certified laboratory. Forty-nine respondents completed the survey; 41 % of participants reported board certification in genetic counseling. Pre-test and post-test counseling was completed in all but one case each. Pre-test counseling lasted less than 1 h for 53 % of cases and 1 to 2 h for 43 %. Topics discussed with all patients included consent for testing, and incidental findings; other topics were variable. In contrast to pre-test counseling, 59 % reported post-test counseling lasting 1 to 2 h and 33 % less than an hour; post testing counseling was significantly longer in cases with a definitive diagnosis than those without (p = 0.0129). The survey findings indicate some variability regarding the amount of time spent on counseling and the topics discussed during pre-test counseling. Additional exploration, patient and provider educational resources, and potentially more specific guidelines regarding counseling for WES may be warranted. PMID- 26283064 TI - Regal electrochemistry: British 5 pence coins provide useful metallic macroelectrode substrates. AB - The utilisation of British Currency (GBP) as an electrode substrate is demonstrated for the first time. Termed Regal electrochemistry, a 5 pence (5p) coin (GBP) is electrically wired using a bespoke electrochemical cell and is electrochemically characterised using the outer-sphere redox probe hexaammineruthenium(III) chloride. The electroanalytical utility of the 5p coin electrode is demonstrated towards the novel, proof-of-concept sensing of lead(II) ions using square-wave voltammetry in model buffer solutions over the linear range 5-2000 nM exhibiting a limit of detection (3sigma) of 1.97 nM. Interestingly, the actual cost of the electrode is 2.5 pence (GBP) since both sides of the coins can be utilised and provide a cheap yet reproducible and disposable metallic electrode substrate that is electrochemically useful. PMID- 26283063 TI - Does parental drinking influence children's drinking? A systematic review of prospective cohort studies. AB - AIMS: To evaluate evidence of the capacity for causal inference in studies of associations between parental and offspring alcohol consumption in the general population. METHODS: A systematic search for, and narrative analysis of, prospective cohort studies of the consequences of drinking, except where assessed prenatally only, or with clinically derived instruments. Primary outcome measures were alcohol use or related problems in offspring, which were collected at least 3 years after exposure measures of parental drinking. The systematic review included 21 studies comprising 26,354 families or parent-child dyads with quantitative effect measures available for each study. Criteria for capacity of causal inference included (1) theory-driven approach and analysis; (2) analytical rigour; and (3) minimization of sources of bias. RESULTS: Four of the 21 included studies filled several, but not all, criteria and were assessed to have some capacity for causal inference. These four studies found some evidence that parental drinking predicted drinking behaviour in adolescent offspring. The remaining 17 studies had little or no such capacity. CONCLUSIONS: There is a fairly large and consistent literature demonstrating that more parental drinking is associated with more drinking in offspring. Despite this, existing evidence is insufficient to warrant causal inferences at this stage. PMID- 26283066 TI - Community of thermoacidophilic and arsenic resistant microorganisms isolated from a deep profile of mine heaps. AB - Soluble arsenic (As) in acidic feed solution may inhibit the copper (Cu) bioleaching process within mine heaps. To clarify the effect of soluble arsenic on the live biomass and bioxidative activity in heaps, toxicological assays were performed using a synthetic feed solution given by a mine company. The microorganisms had previously been isolated from two heap samples at up to 66 m depth, and cultured using specific media for chemolithotrophic acidophiles (pH 1 2) and moderate thermophiles (48 degrees C), for arsenic tolerance assay. The four media with the highest biomass were selected to assay As-resistance; one culture (Q63h) was chosen to assay biooxidative activity, using a heap sample that contained chalcopyrite and covellite. We found that 0.5 g/L of As does not affect living biomass or biooxidative activity on Cu sulfides, but it dissolves Cu, while As precipitates as arsenic acid (H3AsO4.1/2H2O). The arsenic tolerant community, as identified by 16S rDNA gene sequence analysis, was composed of three main metabolic groups: chemolithotrophs (Leptospirillum, Sulfobacillus); chemolithoheterotrophs and organoheterotrophs as Acidovorax temperans, Pseudomonas alcaligenes, P. mendocina and Sphingomonas spp. Leptospirillum spp. and S. thermosulfidooxidans were the dominant taxa in the Q63-66 cultures from the deepest sample of the oldest, highest-temperature heap. The results indicated arsenic resistance in the microbial community, therefore specific primers were used to amplify ars (arsenic resistance system), aio (arsenite oxidase), or arr (arsenate respiratory reduction) genes from total sample DNA. Presence of arsB genes in S. thermosulfidooxidans in the Q63-66 cultures permits H3AsO4-As(V) detoxification and strengthens the community's response to As. PMID- 26283067 TI - Diagnostic performance of S100B protein serum measurement in detecting intracranial injury in children with mild head trauma. AB - OBJECTIVE: To assess the accuracy of S100B serum level to detect intracranial injury in children with mild traumatic brain injury. METHODS: A multicenter prospective cohort study was carried out in the paediatric emergency departments of three tertiary hospitals in Switzerland between January 2009 and December 2011. Participants included children aged <16 years with a mild traumatic brain injury (GCS >=13) for whom a head CT was requested by the attending physician. Venous blood was obtained within 6 h of the trauma in all children for S100B measurement before a head CT was performed. As the S100B value was not available during the acute care period, the patient's management was not altered. The main measures were protein S100B value and the CT result. RESULTS: 20/73 (27.4%) included children had an intracranial injury detected on CT. S100B receiver operating characteristics area under the curve was 0.73 (95% CI 0.60 to 0.86). With a 0.14 ug/L cut-off point, S100B reached an excellent sensitivity of 95% (95% CI 77% to 100%) and 100% (95% CI 81% to 100%) in all children and in children aged >2 years, respectively. The specificity, however, was 34% (95% CI 27% to 36%) and 37% (95% CI 30% to 37%), respectively. CONCLUSIONS: S100B has an excellent sensitivity but poor specificity. It is therefore an accurate tool to help rule out an intracranial injury but cannot be used as the sole marker owing to its specificity. Used with clinical decision rules, S100B may help to reduce the number of unnecessary CT scans. PMID- 26283068 TI - Polymorphic cross-seeding amyloid assemblies of amyloid-beta and human islet amyloid polypeptide. AB - Epidemiological studies have shown that the development of Alzheimer's disease (AD) is associated with type 2 diabetes (T2D), but it still remains unclear how AD and T2D are connected. Heterologous cross-seeding between the causative peptides of Abeta and hIAPP may represent a molecular link between AD and T2D. Here, we computationally modeled and simulated a series of cross-seeding double layer assemblies formed by Abeta and hIAPP peptides using all-atom and coarse gained molecular dynamics (MD) simulations. The cross-seeding Abeta-hIAPP assemblies showed a wide range of polymorphic structures via a combination of four beta-sheet-to-beta-sheet interfaces and two packing orientations, focusing on a comparison of different matches of beta-sheet layers. Two cross-seeding Abeta-hIAPP assemblies with different interfacial beta-sheet packings exhibited high structural stability and favorable interfacial interactions in both oligomeric and fibrillar states. Both Abeta-hIAPP assemblies displayed interfacial dehydration to different extents, which in turn promoted Abeta-hIAPP association depending on interfacial polarity and geometry. Furthermore, computational mutagenesis studies revealed that disruption of interfacial salt bridges largely disfavor the beta-sheet-to-beta-sheet association, highlighting the importance of salt bridges in the formation of cross-seeding assemblies. This work provides atomic-level information on the cross-seeding interactions between Abeta and hIAPP, which may be involved in the interplay between these two disorders. PMID- 26283069 TI - Characterization of chronic and acute ESA hyporesponse: a retrospective cohort study of hemodialysis patients. AB - BACKGROUND: Some patients with chronic kidney disease do not respond adequately to erythropoiesis-stimulating agent (ESA) treatment; these patients are referred to as ESA hyporesponders. There is no widely accepted contemporary definition for chronic ESA hyporesponse. The study objective was to propose and validate an operational definition for chronic ESA hyporesponse. METHODS: This was a retrospective cohort study using electronic health care records. Participants were anemic hemodialysis patients treated during February 2012 and were followed for 15 months. Patients' ESA response (responders) or lack of response (chronic and acute hyporesponders) based on longitudinal patterns of ESA dose and hemoglobin level was assessed. Persistence of hyporesponse, longitudinal iron measures, transfusion rates, and mortality rates were analyzed. Frequency of blood transfusions (monthly) and death rates (quarterly) were calculated. Log normalized serum ferritin concentration was analyzed. RESULTS: Of 97,677 eligible patients, 6632 had acute hyporesponsiveness (ESA responsiveness restituted in <= 4 months) and 3086 had chronic hyporesponsiveness (lack of ESA response for > 4 months). Over months 1-4 among chronic hyporesponders, mean serum ferritin (722 785 ng/mL) and transferrin saturation (TSAT; 26.76 %-27.08 %) were constant, while acute hyporesponsive patients experienced increased ferritin (654-760 ng/mL) and TSAT (25.71-30.88 %) levels. Compared to ESA responders (0.19-0.30 %), chronic hyporesponders were transfused 7-times (1.20-2.17 %) more frequently over follow-up. Quarterly mortality was greatest in chronic ESA hyporesponders (2.98 5.48 %), followed by acute ESA hyporesponders (2.17-3.30 %) and ESA responders (1.43-2.49 %). With consistence over the study, chronic hyporesponders died more frequently than patients in the other study cohorts. CONCLUSIONS: Findings indicate that 4 months of continuous ESA hyporesponsiveness can be used to differentiate acute from chronic hyporesponsiveness. This definition of chronic hyporesponsiveness is supported by outcome data showing higher mortality and transfusion rates in chronic hyporesponders compared to acute hyporesponders. PMID- 26283070 TI - Ultrastructural changes in the melanocytes of aging human choroid. AB - Retinal pigment epithelial cells as well as choroidal melanocytes (CM) possess melanin granules. The former show clear, age-related changes (formation of lipofuscin granules with a concomitant decrease in melanin content); however, data on changes in the CM with aging are fairly limited. We examined CM in human macular and mid-peripheral areas by light- and transmission electron microscopy in 50-94 year-old donor eyes (N=12). Unlike in the choroid of lower ages, the melanocytes from aging choroid (>75 years) showed partial fusion of about 8-15 melanosomes, forming rosettes-like structures. Besides, there was evidence of emptiness in cytoplasm caused by the loss of melanosomes in aged CM, as was confirmed by quantification in macular part of choroid. In advanced aged eyes (85 94-year-old), the CM possessed many lipid droplets as well as irregular lipofuscin granules, the latter had a tendency to fuse with melanosomes, as happens in aged retinal pigment epithelium. Macrophages in their cytoplasm contained abundant irregular as well as clumped melanosomes of variable size, suggesting that damaged granules/melanocytes are cleared by these phagocytes. These obvious changes in the CM are likely to make the choroid prone to damage by visible light. PMID- 26283071 TI - Sick-leave and help seeking among rescue workers after the terror attacks in Norway, 2011. AB - BACKGROUND: Several studies have addressed psychological problems after terror attacks, especially among victims. Fewer have addressed possible health consequences among rescue workers involved with terror attacks. This study's aim was to investigate the levels of sick-leave and psychological help seeking among rescue workers involved in the terror attacks in Norway on July 22, 2011, and to identify associations between sick-leave and background-, exposure- and work related variables. METHODS: This cross-sectional study included five groups of professional rescue personnel and one group of unaffiliated volunteers. The questionnaire was distributed approximately 10 months after the terror attacks, with a response rate of 61.3 % (N = 1790). RESULTS: A total of 9.7 % of participants self-reported sick-leave. The rate varied from 2.4 % among police officers to 14.5 % among unaffiliated volunteers, p < .001. There were 0.0-1.2 % of the professionals who were on sick-leave for more than 2 weeks and 5.5 % among the unaffiliated volunteers. More unaffiliated volunteers (42.6 %) and psychosocial personnel (16.3 %) consulted a psychologist or psychiatrist compared to other groups (3-9 %), p < .001. General healthcare providers (OR 6.1), psychosocial personnel (OR 6.3) and unaffiliated volunteers (OR 5.7) were associated with sick-leave, together with unwanted stress reactions (OR 1.6) and starting work on July 22 (OR 1.6). CONCLUSIONS: A small minority of professional rescue workers reported sick-leave for more than 2 weeks, and few had sought psychological help. Unaffiliated volunteers reported more stress symptoms, longer sick-leave duration and more psychological help seeking. This group may benefit from more support. PMID- 26283072 TI - When are sex-specific effects really sex-specific? AB - We examined developmental programming studies that reported sex-specific effects published between 2012 and 2014, and examined whether the authors reported a statistical approach to explicitly test whether the effect of treatment differed between the sexes, for example, a sex by treatment interaction term. Less than half of the studies that reported sex-specific effects described explicitly testing whether effects were indeed sex-specific; in most cases, an effect was considered 'sex-specific' if it was significant in one sex but not the other. This is not a robust approach, since significance in one sex and lack of significance in the other sex does not imply a significant difference between the sexes. However, sample size often limits statistical power to detect interactions. We suggest that if the effect is significant in only one sex, but the interaction term is not significant, alternative solutions would be to present the confidence intervals for the effect size for each sex, or using Bayesian approaches to calculate the probability that the effect sizes differ between the sexes. We present a simple example of a Bayesian analysis to illustrate that this approach is reasonably easy to implement and interpret. PMID- 26283073 TI - Venturing beyond the Levy flight foraging hypothesis: Reply to comments on "Liberating Levy walk research from the shackles of optimal foraging". PMID- 26283076 TI - BMA attacks government for "chasing headlines" instead of tackling NHS problems. PMID- 26283074 TI - Identifying the role of pre-and postsynaptic GABA(B) receptors in behavior. AB - Although many reviews exist characterizing the molecular differences of GABAB receptor isoforms, there is no current review of the in vivo effects of these isoforms. The current review focuses on whether the GABAB1a and GABAB1b isoforms contribute differentially to behaviors in isoform knockout mice. The roles of these receptors have primarily been characterized in cognitive, anxiety, and depressive phenotypes. Currently, the field supports a role of GABAB1a in memory maintenance and protection against an anhedonic phenotype, whereas GABAB1b appears to be involved in memory formation and a susceptibility to developing an anhedonic phenotype. Although GABAB receptors have been strongly implicated in drug abuse phenotypes, no isoform-specific work has been done in this field. Future directions include developing site-specific isoform knockdown to identify the role of different brain regions in behavior, as well as identifying how these isoforms are involved in development of behavioral phenotypes. PMID- 26283075 TI - The pre-ECMO simplified acute physiology score II as a predictor for mortality in patients with initiation ECMO support at the emergency department for acute circulatory and/or respiratory failure: a retrospective study. AB - BACKGROUND: In the emergency department (ED), extracorporeal membrane oxygenation (ECMO) can be used as a rescue treatment modality for patients with refractory circulatory and/or respiratory failure. Serious consideration must be given to the indication, and the PRESERVE and RESP scores for mortality have been investigated. However these scores were validated to predict survival in patients who received mainly veno-venous (VV) ECMO in the intensive care unit. The aim of the present study was to investigate the factors that predicted the outcomes for patients who received mixed mode (veno-arterial [VA] and VV) ECMO support in the ED. METHODS: This single center retrospective study included 65 patients who received ECMO support at the ED for circulatory or respiratory failure between January 2009 and December 2013. Pre-ECMO SAPS II and other variables were evaluated and compared for predicting mortality. RESULTS: Fifty-four percent of patients received ECMO-cardiopulmonary resuscitation (E-CPR), 31 % received VA and V-AV ECMO, and 15 % received VV ECMO. The 28-day and 60-month mortality rates were 52 % and 63 %. In the multivariate analysis, only the pre-ECMO Simplified Acute Physiology Score II (SAPS II) (odd ratio: 1.189, 95 % confidence interval: 1.032-1.370, p = 0.016) could predict the 28-day mortality. The area under the receiver operating characteristic curve and the optimal cutoff value for pre-ECMO SAPS II in predicting 28-day mortality was 0.852 (95 % CI: 0.753-0.951, p < 0.001) and 80 (sensitivity of 97.1 % and specificity of 71.0 %), respectively. Validation of the 80 cutoff value revealed a statistically significant difference for the 28-day and 60-month mortality rates in the overall, E-CPR, and VA groups (28-day: p < 0.001, p = 0.004, p = 0.005; 60-month: p < 0.001, p = 0.004, p = 0.020). In the Kaplan-Meier analysis, the 28-day and 60-month survival rates were lower among the patients with a pre-ECMO SAPS II of <= 80, compared to those with a score of > 80 (both, p < 0.001). CONCLUSION: The pre-ECMO SAPS II could be helpful for identifying patients with refractory acute circulatory and/or respiratory failure who will respond to ECMO support in the ED. PMID- 26283077 TI - Hyperelastic models for hydration of cellular tissue. AB - In this paper we present hyperelastic models for swelling elastic shells, due to pressurization of the internal cavity. These shells serve as model systems for cells having cell walls, as can be found in bacteria, plants and fungi. The pressurized internal cavity represents the cell vacuole with intact membrane at a certain turgor pressure, and the elastic shell represents the hydrated cell wall. At pressurization the elastic shell undergoes inhomogeneous deformation. Its deformation is governed by a strain energy function. Using the scaling law of Cloizeaux for the osmotic pressure, we obtain approximate analytical expressions of the cell volume versus turgor pressure - which are quite comparable to numerical solutions of the problem. Subsequently, we have simulated the swelling of shells - where the cell wall material is embedded with microfibrils, leading to strain hardening and anisotropic cell expansion. The purpose of our investigations is to elucidate the contribution of cell membrane integrity and turgor to the water holding capacity (hydration) of plant foods. We conclude with a discussion of the impact of this work on the hydration of food material, and other fields like plant science and the soft matter physics of responsive gels. PMID- 26283079 TI - Reduced patient restrictions following total hip arthroplasty: study protocol for a randomized controlled trial. AB - BACKGROUND: Total hip arthroplasty (THA) is a very common procedure in orthopedic surgery. In the Netherlands, 25,642 primary THAs were performed in 2013. Postoperative hip dislocation is one of the major complications and has been reported in 0.5 to 10.6 % of patients after primary THA. Several reports regarding the use of an anterolateral surgical approach have shown that a non restriction or reduced restriction protocol does not increase the dislocation rate. For the posterolateral surgical approach it has been suggested that patient restrictions might be unnecessary but the amount of available literature is scarce. As such, randomized controlled trials aimed at investigating restrictions following THA using a posterior approach are strongly recommended. The aim of this prospective randomized controlled trial is to investigate the non inferiority hypothesis concerning the early dislocation rate after THA in patients with and without the use of a reduced restriction protocol. METHODS/DESIGN: After providing informed consent a group of 456 patients with symptomatic coxarthrosis will be randomized to receive a THA either with care as usual, i.e. receiving postoperative restrictions including the advice to sleep in a supine position for the first 8 weeks postoperatively, or reduced restrictions with no recommendations regarding the position during sleeping. Primary outcome measure will be the percentage of early dislocations within the first 8 weeks after THA. Secondary outcome measures will be patient satisfaction, time to functional recovery, quality of sleep and patient's self-reported compliance with postoperative instructions. DISCUSSION: To our knowledge this will be the first randomized controlled trial that compares a reduced restriction protocol with a restricted protocol following THA using a posterolateral surgical approach. Our hypothesis is that a reduced restriction protocol following THA with use of a posterolateral surgical approach has no influence on the early dislocation rate compared to a restricted protocol. Instead, embracing a reduced restriction protocol might even contribute to a higher quality of sleep, thereby facilitating a faster uptake and return to daily functions in patients after THA. TRIAL REGISTRATION: ClinicalTrials.gov NCT02107248 , registration date 3 April 2014. PMID- 26283080 TI - Molecular Determinants for Unphosphorylated STAT3 Dimerization Determined by Integrative Modeling. AB - Signal transducer and activator of transcription factors (STATs) are proteins that can translocate into the nucleus, bind DNA, and activate gene transcription. STAT proteins play a crucial role in cell proliferation, apoptosis, and differentiation. The prevalent view is that STAT proteins are able to form dimers and bind DNA only upon phosphorylation of specific tyrosine residues in the transactivation domain. However, this paradigm has been questioned recently by the observation of dimers of unphosphorylated STATs (USTATs) by X-ray, Forster resonance energy transfer, and site-directed mutagenesis. A more complex picture of the dimerization process and of the role of the dimers is, thus, emerging. Here we present an integrated modeling study of STAT3, a member of the STAT family of utmost importance in cancer development and therapy, in which we combine available experimental data with several computational methodologies such as homology modeling, protein-protein docking, and molecular dynamics to build reliable atomistic models of USTAT3 dimers. The models generated with the integrative approach presented here were then validated by performing computational alanine scanning for all the residues in the protein-protein interface. These results confirmed the experimental observation of the importance of some of these residues (in particular Leu78 and Asp19) in the USTAT3 dimerization process. Given the growing importance of USTAT3 dimers in several cellular pathways, our models provide an important tool for studying the effects of pathological mutations at the molecular and/or atomistic level, and in the rational design of new inhibitors of dimerization. PMID- 26283078 TI - Characterization of Three-Dimensional Retinal Tissue Derived from Human Embryonic Stem Cells in Adherent Monolayer Cultures. AB - Stem cell-based therapy of retinal degenerative conditions is a promising modality to treat blindness, but requires new strategies to improve the number of functionally integrating cells. Grafting semidifferentiated retinal tissue rather than progenitors allows preservation of tissue structure and connectivity in retinal grafts, mandatory for vision restoration. Using human embryonic stem cells (hESCs), we derived retinal tissue growing in adherent conditions consisting of conjoined neural retina and retinal pigment epithelial (RPE) cells and evaluated cell fate determination and maturation in this tissue. We found that deriving such tissue in adherent conditions robustly induces all eye field genes (RX, PAX6, LHX2, SIX3, SIX6) and produces four layers of pure populations of retinal cells: RPE (expressing NHERF1, EZRIN, RPE65, DCT, TYR, TYRP, MITF, PMEL), early photoreceptors (PRs) (coexpressing CRX and RCVRN), inner nuclear layer neurons (expressing CALB2), and retinal ganglion cells [RGCs, expressing BRN3B and Neurofilament (NF) 200]. Furthermore, we found that retinal progenitors divide at the apical side of the hESC-derived retinal tissue (next to the RPE layer) and then migrate toward the basal side, similar to that found during embryonic retinogenesis. We detected synaptogenesis in hESC-derived retinal tissue, and found neurons containing many synaptophysin-positive boutons within the RGC and PR layers. We also observed long NF200-positive axons projected by RGCs toward the apical side. Whole-cell recordings demonstrated that putative amacrine and/or ganglion cells exhibited electrophysiological responses reminiscent of those in normal retinal neurons. These responses included voltage gated Na(+) and K(+) currents, depolarization-induced spiking, and responses to neurotransmitter receptor agonists. Differentiation in adherent conditions allows generation of long and flexible pieces of 3D retinal tissue suitable for isolating transplantable slices of tissue for retinal replacement therapies. PMID- 26283081 TI - Effect of ethylene glycol dimethacrylate on swelling and on metformin hydrochloride release behavior of chemically crosslinked pH-sensitive acrylic acid-polyvinyl alcohol hydrogel. AB - BACKGROUND: The present work objective was to prepare and to observe the effect of ethylene glycol dimethacrylate on swelling and on drug release behavior of pH sensitive acrylic acid-polyvinyl alcohol hydrogel. METHODS: In the present work, pH sensitive acrylic acid-polyvinyl alcohol hydrogels have been prepared by free radical polymerization technique in the presence of benzoyl peroxide as an initiator. Different crosslinker contents were used to observe its effect on swelling and on drug release. Dynamic and equilibrium swelling studies of prepared hydrogels were investigated in USP phosphate buffer solutions of pH 1.2, 5.5, 6.5 and 7.5 with constant ionic strengths. Hydrogels were evaluated for polymer volume fraction, solvent interaction parameter, molecular weight between crosslinks, number of links per polymer chain, diffusion coefficient, sol-gel fraction and porosity. To demonstrate the release pattern of the drug, zero order, first-order, higuchi and korsmeyer-peppas models were applied. Quality and consistency of hydrogels was examined by FTIR and surface morphology of hydrogels was examined by SEM. RESULTS: Decrease in swelling and in drug release was seen by increasing content of ethylene glycol dimethacrylate. A remarkable high swelling was observed at high pH indicating the potential of this hydrogel for delivery of drugs to intestine. By increasing the concentration of ethylene glycol dimethacrylate, porosity decreased. Order of release was observed first order in all cases and the mechanism was non-fickian diffusion. FTIR confirmed the formation of network. SEM results showed the incorporation of drug. CONCLUSION: The prepared hydrogels can be suitably used for targeted drug delivery to the intestine. PMID- 26283082 TI - Hepatotoxicity and pharmacokinetics of cisplatin in combination therapy with a traditional Chinese medicine compound of Zengmian Yiliu granules in ICR mice and SKOV-3-bearing nude mice. AB - BACKGROUND: Cisplatin (CDDP) is a highly effective chemotherapeutic agent used for therapy of many tumors and has been limited by its toxicity. Zengmian Yiliu granule (ZMYL), a compound preparation of traditional Chinese medicines, has been used in clinic as a complementary and alternative medicine for attenuating CDDP induced toxicities and enhancing the tumor therapeutic effect of CDDP. The aim of the present study is to investigate hepaprotective effect of ZMYL against CDDP induced hepatotoxicity. Further, the pharmacokinetic characteristics of CDDP in SKOV-3-bearing nude mice were observed. METHODS: The ICR mice were dosed orally with ZMYL for 7 days and then CDDP was injected intraperitoneally at a dose of 45 mg/kg body weight. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured to evaluate the liver function. The total glutathione (T-GSH), reduced glutathione (GSH) and glutathione S transferase (GST) levels were determined to evaluate the oxidant damage in liver homogenates. Tissue pathological change in liver was conducted by light microscopy analysis. The pharmacokinetic and tissue distribution of free and total platinum (Pt) after dosing of CDDP alone and combination with ZMYL were determined in SKOV-3-bearing nude mice by ICP-MS. RESULTS: Oral administration of ZMYL prior to the CDDP treatment could prevent the CDDP-induced in lifting of ALT and AST, reduction of T-GSH, R-GSH and GST, and some histopathological alterations in ICR mice. Some differences in pharmacokinetic parameters between the two groups have been observed in higher CL and decreased MRT of free platinum (Pt) in plasma and total Pt in spleen in CDDP co-administration with ZMYL group. It indicated CDDP was cleared more quickly from blood and spleen, and could reduce the accumulation and toxic possibility of CDDP in combination with ZMYL. CONCLUSIONS: ZMYL could be used as a beneficial supplement, which could attenuate CDDP-induced hepatotoxicity during CDDP chemotherapy and did not disturb the pharmacokinetics fate of CDDP significantly. PMID- 26283083 TI - Platelets in the 'Code Red' transfusion request policy initiated by pre-hospital physicians. PMID- 26283084 TI - Defining major trauma using the 2008 Abbreviated Injury Scale. AB - BACKGROUND: The Injury Severity Score (ISS) is the most ubiquitous summary score derived from Abbreviated Injury Scale (AIS) data. It is frequently used to classify patients as 'major trauma' using a threshold of ISS >15. However, it is not known whether this is still appropriate, given the changes which have been made to the AIS codeset since this threshold was first used. This study aimed to identify appropriate ISS and New Injury Severity Score (NISS) thresholds for use with the 2008 AIS (AIS08) which predict mortality and in-hospital resource use comparably to ISS >15 using AIS98. METHODS: Data from 37,760 patients in a state trauma registry were retrieved and reviewed. AIS data coded using the 1998 AIS (AIS98) were mapped to AIS08. ISS and NISS were calculated, and their effects on patient classification compared. The ability of selected ISS and NISS thresholds to predict mortality or high-level in-hospital resource use (the need for ICU or urgent surgery) was assessed. RESULTS: An ISS >12 using AIS08 was similar to an ISS >15 using AIS98 in terms of both the number of patients classified major trauma, and overall major trauma mortality. A 10% mortality level was only seen for ISS 25 or greater. A NISS >15 performed similarly to both of these ISS thresholds. However, the AIS08-based ISS >12 threshold correctly classified significantly more patients than a NISS >15 threshold for all three severity measures assessed. CONCLUSIONS: When coding injuries using AIS08, an ISS >12 appears to function similarly to an ISS >15 in AIS98 for the purposes of identifying a population with an elevated risk of death after injury. Where mortality is a primary outcome of trauma monitoring, an ISS >12 threshold could be adopted to identify major trauma patients. LEVEL OF EVIDENCE: Level II evidence--diagnostic tests and criteria. PMID- 26283085 TI - Dose-finding evaluation of once-daily treatment with olodaterol, a novel long acting beta2-agonist, in patients with asthma: results of a parallel-group study and a crossover study. AB - BACKGROUND: Olodaterol is a novel, inhaled long-acting beta2-agonist (LABA) with >24-hour duration of action investigated in asthma and chronic obstructive pulmonary disease. METHODS: Two multicentre studies examined the efficacy and safety of 4 weeks' once-daily (QD) olodaterol (2, 5, 10 and 20 MUg, with background inhaled corticosteroids) in patients with asthma. One randomised, double-blind, parallel-group study (1222.6; 296 patients) administered treatment in the morning. Pulmonary function tests (PFTs) were performed pre-dose (trough) and <=3 hours post-dose (weeks 1 and 2), and <=6 hours post-dose after 4 weeks; primary end point was trough forced expiratory volume in 1 second (FEV1) response (change from baseline mean FEV1) after 4 weeks. A second randomised, double blind, placebo- and active-controlled (formoterol 12 MUg twice-daily) incomplete block crossover study (1222.27; 198 patients) administered QD treatments in the evening. PFTs were performed over a 24-hour dosing interval after 4 weeks; primary end point was FEV1 area under the curve from 0-24 hours (AUC0-24) response (change from study baseline [mean FEV1] after 4 weeks). RESULTS: Study 1222.6 showed a statistically significant increase in trough FEV1 response with olodaterol 20 MUg (0.147 L; 95 % confidence interval [CI]: 0.059, 0.234; p = 0.001) versus placebo, with more limited efficacy and no evidence of dose response compared to placebo across the other olodaterol doses (2, 5 and 10 MUg). Study 1222.27 demonstrated increases in FEV1 AUC0-24 responses at 4 weeks with all active treatments (p < 0.0001); adjusted mean (95 % CI) differences from placebo were 0.140 (0.097, 0.182), 0.182 (0.140, 0.224), 0.205 (0.163, 0.248) and 0.229 (0.186, 0.272) L for olodaterol 2, 5, 10 and 20 MUg, respectively, and 0.169 (0.126, 0.211) for formoterol, providing evidence of increased efficacy with higher olodaterol dose. Olodaterol was generally well tolerated, with a few events associated with known sympathomimetic effects, mainly with 20 MUg. CONCLUSIONS: The LABA olodaterol has >24-hour duration of action. In patients with asthma, evidence of bronchodilator efficacy was demonstrated with statistically and clinically significant improvements in the primary end point of trough FEV1 response measured in clinics over placebo for the highest administered dose of 20 MUg in Study 1222.6, and statistically and clinically significant improvements versus placebo in FEV1 AUC0-24 responses at 4 weeks for all doses tested in Study 1222.27, which also exhibited a dose response. Bronchodilator efficacy was seen over placebo for all olodaterol doses for morning and evening peak expiratory flow in both studies. All doses were well tolerated. TRIAL REGISTRATIONS: NCT00467740 (1222.6) and NCT01013753 (1222.27). PMID- 26283087 TI - Invited Commentary: Multigenerational Social Determinants of Health-Opportunities and Challenges. AB - An emerging area of social epidemiology examines the relationship between grandparental education and grandchild health. In an accompanying article, Huang et al. (Am J Epidemiol. 2015;182(7):568-578) join the small but growing body of research on this topic. It is useful to contextualize Huang et al.'s work within the much larger body of research examining relationships between education and health within a single generation or across 2 generations. These investigators have generally concluded that higher educational attainment is robustly associated with better health. There are many potential mechanisms through which education and other social exposures may affect health outcomes in a single generation or across generations, and estimating direct and indirect effects can be helpful for assessing specific mechanisms. Researchers conducting multigenerational analyses are faced with several challenges, including limited availability of data for some measures (e.g., educational attainment, and sometimes for 1 grandparent only), limited age ranges of participants, disparate social and political contexts in which study participants of different generations have lived, and patterns of social class reproduction. We encourage future researchers to weave together the careful analytical considerations illustrated by Huang et al. with a rich understanding of the social context for each of the generations studied to help overcome these challenges and advance our understanding of multigenerational social determinants of health. PMID- 26283086 TI - Are Early-Life Socioeconomic Conditions Directly Related to Birth Outcomes? Grandmaternal Education, Grandchild Birth Weight, and Associated Bias Analyses. AB - Grandmaternal education may be related to grandchild birth weight (GBW) through maternal early-life development; however, conventional regression models may be endogenously confounded. Alternative models employing explicit structural assumptions may provide incrementally clearer evidence. We used data from the US National Longitudinal Study of Adolescent to Adult Health (1995-2009; 1,681 mother-child pairs) to estimate "direct effects" of grandmaternal educational level (less than high school, high school diploma or equivalent, or college degree) at the time of the mother's birth on GBW, adjusted for maternal life course factors: maltreatment as a child, education and income as an adult, prepregnancy overweight, and prenatal smoking. Using conventional and marginal structural model (MSM) approaches, we estimated 54-g (95% confidence interval: 14.0, 122.1) and 87-g (95% confidence interval: 10.9, 162.5) higher GBWs per increase in educational level, respectively. The MSM allowed simultaneous mediation by and adjustment for prepregnancy overweight. Estimates were insensitive to alternate structural assumptions and mediator parameterizations. Bias analysis suggested that a single unmeasured confounder would have to have a strong influence on GBW (approximately 150 g) or be greatly imbalanced across exposure groups (approximately 25%) to completely explain the findings. Coupling an MSM with sensitivity analyses provides some evidence that maternal early-life socioeconomic environment is directly associated with offspring birth weight. PMID- 26283089 TI - Huang et al. Respond to "Multigenerational Social Determinants of Health". PMID- 26283090 TI - Simple Estimation of Patient-Oriented Effects From Randomized Trials: An Open and Shut CACE. AB - In randomized controlled trials, the intention-to-treat estimator provides an unbiased estimate of the causal effect of treatment assignment on the outcome. However, patients often want to know what the effect would be if they were to take the treatment as prescribed (the patient-oriented effect), and several researchers have suggested that the more relevant causal effect for this question is the complier average causal effect (CACE), also referred to as the local average treatment effect. Sophisticated approaches to estimating the CACE include Bayesian and frequentist methods for principal stratification, inverse probability-of-treatment-weighted estimators, and instrumental-variable (IV) analysis. All of these approaches exploit information about adherence to assigned treatment to improve upon the intention-to-treat estimator, but they are rarely used in practice, probably because of their complexity. The IV principal stratification estimator is simple to implement but has had limited use in practice, possibly due to lack of familiarity. Here, we show that the IV principal stratification estimator is a modified per-protocol estimator that should be obtainable from any randomized controlled trial, and we provide a closed form for its robust variance (and its uncertainty). Finally, we illustrate sensitivity analyses we conducted to assess inference in light of potential violations of the exclusion restriction assumption. PMID- 26283091 TI - Invited Commentary: The Association Between Marijuana Use and Male Reproductive Health. AB - Approximately 15% of all couples are unable to conceive after a year and are labeled infertile. In recent years, increasing attention has been given to lifestyle factors that may impact fertility. In the United States, it is estimated that there are more than 17 million current users of marijuana with 4.6 million using marijuana almost daily. Although common, to date, little data exist on the impact of marijuana use on male fertility. In the current issue of the Journal, Gundersen et al. (Am J Epidemiol. 2015;182(6):473-481) provide data examining the relationship between marijuana use and semen quality from young men recruited out of the general Danish population. Men who reported daily marijuana use displayed significant lower sperm concentration and sperm counts compared with nonusers, while testosterone levels were higher. The current report provides important information for patients and providers regarding the negative association of marijuana use on semen quality. Although the benefit of marijuana cessation on recovery is uncertain, further study on the impact of marijuana use on male reproductive health is warranted as more states explore marijuana legalization. PMID- 26283092 TI - Association Between Use of Marijuana and Male Reproductive Hormones and Semen Quality: A Study Among 1,215 Healthy Young Men. AB - A total of 1,215 young Danish men aged 18-28 years were recruited between 2008 and 2012 when they attended a compulsory medical examination to determine their fitness for military service. The participants delivered a semen sample, had a blood sample drawn, and underwent a physical examination. They responded to questionnaires including information on marijuana and recreational drug use during the past 3 months (no use, use once per week or less, or use more than once per week). A total of 45% had smoked marijuana within the last 3 months. Regular marijuana smoking more than once per week was associated with a 28% (95% confidence interval (CI): -48, -1) lower sperm concentration and a 29% (95% CI: 46, -1) lower total sperm count after adjustment for confounders. The combined use of marijuana more than once per week and other recreational drugs reduced the sperm concentration by 52% (95% CI: -68, -27) and total sperm count by 55% (95% CI: -71, -31). Marijuana smokers had higher levels of testosterone within the same range as cigarette smokers. Our findings are of public interest as marijuana use is common and may be contributing to recent reports of poor semen quality. PMID- 26283093 TI - PhosphOrtholog: a web-based tool for cross-species mapping of orthologous protein post-translational modifications. AB - BACKGROUND: Most biological processes are influenced by protein post translational modifications (PTMs). Identifying novel PTM sites in different organisms, including humans and model organisms, has expedited our understanding of key signal transduction mechanisms. However, with increasing availability of deep, quantitative datasets in diverse species, there is a growing need for tools to facilitate cross-species comparison of PTM data. This is particularly important because functionally important modification sites are more likely to be evolutionarily conserved; yet cross-species comparison of PTMs is difficult since they often lie in structurally disordered protein domains. Current tools that address this can only map known PTMs between species based on known orthologous phosphosites, and do not enable the cross-species mapping of newly identified modification sites. Here, we addressed this by developing a web-based software tool, PhosphOrtholog ( www.phosphortholog.com ) that accurately maps protein modification sites between different species. This facilitates the comparison of datasets derived from multiple species, and should be a valuable tool for the proteomics community. RESULTS: Here we describe PhosphOrtholog, a web-based application for mapping known and novel orthologous PTM sites from experimental data obtained from different species. PhosphOrtholog is the only generic and automated tool that enables cross-species comparison of large-scale PTM datasets without relying on existing PTM databases. This is achieved through pairwise sequence alignment of orthologous protein residues. To demonstrate its utility we apply it to two sets of human and rat muscle phosphoproteomes generated following insulin and exercise stimulation, respectively, and one publicly available mouse phosphoproteome following cellular stress revealing high mapping and coverage efficiency. Although coverage statistics are dataset dependent, PhosphOrtholog increased the number of cross-species mapped sites in all our example data sets by more than double when compared to those recovered using existing resources such as PhosphoSitePlus. CONCLUSIONS: PhosphOrtholog is the first tool that enables mapping of thousands of novel and known protein phosphorylation sites across species, accessible through an easy-to-use web interface. Identification of conserved PTMs across species from large-scale experimental data increases our knowledgebase of functional PTM sites. Moreover, PhosphOrtholog is generic being applicable to other PTM datasets such as acetylation, ubiquitination and methylation. PMID- 26283095 TI - Design improvement and performance evaluation of solar photocatalytic reactor for industrial effluent treatment. AB - This work reports the details of the design components and materials used in a linear compound parabolic trough reactor constructed with an aim to use the photocatalyst for solar photocatalytic applications. A compound parabolic trough reactor has been designed and engineered to exploit both UV and visible part of the solar irradiation. The developed compound parabolic trough reactor could receive almost 88% of UV radiation along with a major part of visible radiation. The performance of the reactor has been evaluated in terms of degradation of a probe pollutant using the parameters such as rate constant, residence time and photonic efficiency. An attempt has been made to assess the performance in different ranges of solar spectrum. Finally the developed reactor has been employed for the photocatalytic treatment of a paper mill effluent using Degussa P25 as the photocatalyst. The paper mill effluent collected from Nagaon paper mill, Assam, India has been treated under both batch mode and continuous mode using Degussa P25 photocatalyst under artificial and natural solar radiation, respectively. The photocatalytic degradation kinetics of the paper mill effluent has been determined using the reduction in total organic carbon (TOC) values of the effluent. PMID- 26283094 TI - Long term effects of self-determination theory and motivational interviewing in a web-based physical activity intervention: randomized controlled trial. AB - BACKGROUND: Our main objective in the current study was to evaluate the long-term effectiveness (12 months from baseline) of I Move (a web-based computer tailored physical activity intervention, based on self-determination theory and motivational interviewing). To this end, we compared I Move to a web-based computer tailored physical activity intervention based on traditional health behavior theories (Active Plus), and to a no-intervention control group. As a secondary objective, the present study aimed to identify participant characteristics that moderate the long term effects of I Move and Active Plus. METHODS: A randomized controlled trial was conducted, comparing three research conditions: 1) the I Move condition, participants in this condition received I Move; 2) the Active Plus condition, participants in this condition received Active Plus; 3) the control condition; participants in this condition received no intervention and were placed on a waiting list. Main outcome measures were weekly minutes of moderate to vigorous physical activity and weekly days with minimal 30 min of physical activity. All measurements were taken by web-based questionnaires via the study website. Intervention effects were analyzed using multilevel linear regression analyses. RESULTS: At 12 months from baseline, I Move was found to be effective in increasing weekly minutes of moderate to vigorous physical activity (ES = .13), while Active Plus was not. In contrast, Active Plus was found to be effective in increasing weekly days with >= 30 min PA at 12 months (ES = .11), while I Move was not. No moderators of the effects of I Move were found. CONCLUSIONS: The results suggest that web-based computer tailored physical activity interventions might best include elements based on both self determination theory/motivational interviewing and traditional health behavioral theories. To be more precise, it is arguable that the focus of the theoretical foundations, used in new web-based PA interventions should depend on the intended program outcome. In order to draw firm conclusions, however, more research on the effects of self-determination theory and motivational interviewing in web-based physical activity promotion is needed. TRIAL REGISTRATION: Dutch Trial Register NTR4129. PMID- 26283096 TI - Dynamic Detection of Anti-Human Leukocyte Antigen (HLA) Antibodies but not HLA-DP Loci Mismatches Can Predict Acute Graft-versus-Host Disease and Overall Survival in HLA 12/12-Matched Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies. AB - The National Marrow Donor Program and Center for International Blood and Marrow Transplant Research provided guidelines for the use of anti-HLA antibodies and HLA-DP-mismatched loci in unrelated donor hematopoietic stem cell transplantation (HSCT). However, a deeper understanding of other potentially useful biomarkers for predicting clinical outcomes in HLA-A, -B, -C, -DRB1, -DQB1, and -DQA1 (12/12)-matched unrelated donor HSCT is needed to further improve clinical outcomes. We tested HLA genotyping for 123 pairs of patients and donors. Anti-HLA antibodies using the Luminex method was applied to 123, 117, and 106 serum samples collected before and 1 month and 3 months after transplantation. The presences of anti-HLA antibodies at the 3 time points were 37.4% (46 of 123), 40.2% (47 of 117), and 22.6% (24 of 106). Mismatch of HLA-DPB1 and/or DPA1 allele between patient-donor pairs was 83.6% (92 of 110). Patients with anti-HLA antibodies had delayed platelet recovery. The presence of anti-HLA antibodies and their dynamic changes after transplantation were associated with increased occurrence of grades II to IV acute and chronic graft-versus-host disease (GVHD), higher treatment-related mortality, and reduced overall survival (OS) and disease free survival, especially in acute myeloid leukemia and myelodysplastic syndrome patients. Multivariate analysis showed that presence of anti-HLA antibodies before transplantation was a risk factor for GVHD and OS. Furthermore, HLA-DP loci-matched subgroup showed a trend towards a lower rate of acute GVHD and a higher OS in the anti-HLA Abs-negative group. Our results suggest that dynamic changes of anti-HLA antibodies independently predict for a negative outcome of HSCT, independent of HLA-DP loci mismatches. Routine monitoring for anti-HLA antibody dynamics should be conducted before and after HSCT. PMID- 26283098 TI - A simple route to making counter electrode for dye sensitized solar cells (DSSCs) using sucrose as carbon precursor. AB - Dye sensitized solar cells (DSSCs) have attracted much attention in recent years due to low cost fabrication as compared to silicon-based and thin film solar cells. Though, platinum is an excellent catalytic material for use in preparation of counter electrodes (CEs) for DSSCs it is expensive. Alternatives to replacement of platinum (Pt) that have been examined are carbon materials, conductive polymers and hybrids. In this work, counter electrode for DSSCs was fabricated using carbon material obtained from graphitization of sucrose at high temperature. A slurry of the carbon produced from sucrose graphitization was made with polyvinylpyrrolidone (PVP) as a surfactant and a coating was obtained by doctor blading the slurry over the FTO glass substrate. The current density (Jsc) and open circuit voltage (V(OC)) of fabricated cell (area 0.25 cm(2)) was 10.28 mAc m(-2) and 0.76 V respectively. The efficiency of the cell was 4.33% which was just slightly lower than that obtained for similar cells using platinum based counter electrode. PMID- 26283097 TI - Transformable Peptide Nanocarriers for Expeditious Drug Release and Effective Cancer Therapy via Cancer-Associated Fibroblast Activation. AB - A novel cleavable amphiphilic peptide (CAP) was designed to be specifically responsive to fibroblast activation protein-alpha (FAP-alpha), a protease specifically expressed on the surface of cancer-associated fibroblasts. The CAP self-assembled into fiber-like nanostructures in solution, while the presence of hydrophobic chemotherapeutic drugs readily transformed the assemblies into drug loaded spherical nanoparticles. The disassembly of these nanoparticles (CAP-NPs) upon FAP-alpha cleavage resulted in rapid and efficient release of the encapsulated drugs specifically at tumor sites. This Transformers-like drug delivery strategy could allow them to disrupt the stromal barrier and enhance local drug accumulation. Therapeutic results suggested that drug-loaded CAP-NPs hold promising tumor specificity and therapeutic efficacy for various solid tumor models, confirming its potential utility and versatility in antitumor therapy. PMID- 26283099 TI - In-line coagulation with quaternary amine polymer prior to microfiltration of humic-rich water. AB - This work was designed to investigate the feasibility of using a low molecular weight epichlorohydrin/dimethylamine (epi/DMA) polymer as a primary coagulant for the pretreatment of terrestrial humic-rich water prior to the microfiltration (MF) process, without removal of the flocs produced via the coagulation pretreatment. The main issue explored was the effects of different coagulation conditions on the particle characteristics that would also significantly affect the performance of membranes when filtering coagulated humic-rich water. The size distribution and morphological properties of flocs formed through the coagulation of humic-rich water were characterized and the impact of Ca(2+) on these characteristics that were associated with the performance of the MF membrane was also determined. Epi/DMA additions from 50% to 150% of the charge neutralization dose substantially decreased fouling compared to when filtering raw humic-rich water. Short-term fouling was increased when 1 mM Ca(2+) was added, but the charge neutralization coagulation removed almost all of the fouling tendency that had occurred when filtering Ca-humic solution. The median diameter and the fractal dimension of flocs produced were increased as the zeta potential reached close to zero, which resulted in the formation of a cake layer that was easily removed from the surface of the membrane. PMID- 26283100 TI - Bimetallic PtSn/C catalysts obtained via SOMC/M for glycerol steam reforming. AB - A detailed study on the preparation of bimetallic PtSn/C catalysts using surface controlled synthesis methods, and on their catalytic performance in the glycerol steam reforming reaction has been carried out. In order to obtain these well defined bimetallic phases, techniques derived from Surface Organometallic Chemistry on Metals (SOMC/M) were used. The preparation process involved the reaction between an organometallic compound ((C4H9)4Sn) and a supported transition metal (Pt) in a H2 atmosphere. Catalysts with Sn/Pt atomic ratios of 0.2, 0.3, 0.5, and 0.7 were obtained, and characterized using several techniques: ICP, H2 chemisorption, TEM and XPS. These systems were tested in the glycerol steam reforming varying the reaction conditions (glycerol concentration and reaction temperature). The best performance was observed for the catalysts with the lowest tin contents (PtSn0.2/C and PtSn0.3/C). It was observed that the presence of tin increased the catalysts' stability when working under more severe reaction conditions. PMID- 26283101 TI - Diffusiophoresis of polyelectrolytes: Effects of temperature, pH, type of ionic species and bulk concentration. AB - Extending previous analyses on rigid particles to non-rigid ones, we model the diffusiophoresis of a pH-regulated polyelectrolyte (PE) in a solution containing multiple ionic species. For the first time, the effects of temperature, pH, type of ionic species and bulk concentration are taken into account, and therefore, the conditions considered are more comprehensive and closer to reality than those of the available results in the literature. Numerical simulation is conducted to examine the diffusiophoretic behaviors of a PE under various conditions, and empirical relationships are developed for the dependence of its mobility on the factors mentioned above. We show that temperature and pH influence appreciably the charged conditions of a PE, the ionic diffusivities, and the fluid viscosity, yielding complicated and interesting behaviors that are informative to device design. PMID- 26283102 TI - The angiogenic responses induced by release of angiogenic proteins from tumor cell-activated platelets are regulated by distinct molecular pathways. AB - There is mounting evidence that tumor angiogenesis can be regulated by platelets (Plts), which serve as major sources and delivery vehicles of many proangiogenic cytokines including transforming growth factor-beta and vascular endothelial growth factor. Although considerable progress has been made in understanding the role for Plt secretion in tumor angiogenesis, very little is known about the precise mechanisms underlying cancer cell induction of Plt granule release. Here, we demonstrated that nonsmall cell lung cancer (NSCLC) cells directly induced Plt secretion of several angiogenic regulatory cytokines that promoted angiogenesis in concert. Moreover, we discovered that these Plt-derived angiogenesis modulators were regulated by different molecular pathways and could be largely inhibited by combination of multiple signaling inhibitors. Our present studies indicated that manipulation of Plt secretion of angiogenic cytokines without compromising hemostatic functions could provide a novel option for management of tumor angiogenesis and metastasis in NSCLC patients with thrombocytosis. PMID- 26283103 TI - A prospective study comparing radiographer- and clinician-based localization for patients with metastatic spinal cord compression (MSCC) to assess the feasibility of a radiographer-led service. AB - OBJECTIVE: To investigate whether there was parity between treatment fields localized by radiographers and clinicians, by comparing geographical variations and hence determining the feasibility of a radiographer-led service. METHODS: 23 patients with metastatic spinal cord compression (MSCC) were prospectively sampled. Four radiographers not involved in the original planning performed localization on each patient. The 92 localizations that they determined were compared with the clinician-approved fields. Agreement was defined as <=0.5 cm between field length, width and three isocentre co-ordinates. To be feasible, agreement was required in a minimum of 97% of the cases. The potential time saved with a radiographer-led approach was also recorded. RESULTS: Agreement between clinicians and radiographers was 97.8%. For all field parameters, the average differences were <0.3 cm and were significantly different from the 0.5-cm median (p < 0.0001) that would establish no agreement using Wilcoxon signed-rank test. The average (range) delay awaiting clinician approval was 54 min (4-141 min). CONCLUSION: Strong agreement between radiographer and clinician localizations was established. It was also highlighted that time could be saved in the patient's pathway by removing the need to wait for clinician approval. We believe this supports a radiographer-led service. ADVANCES IN KNOWLEDGE: This article is novel, as it is the first known comparison between clinicians and radiographers in the localization of MSCC radiotherapy. These data show the feasibility of introducing radiographer-led practice and a methodology that could be potentially transferred to investigate the localization parity for other treatment sites. PMID- 26283104 TI - Persistent directional selection on body size and a resolution to the paradox of stasis. AB - Directional selection on size is common but often fails to result in microevolution in the wild. Similarly, macroevolutionary rates in size are low relative to the observed strength of selection in nature. We show that many estimates of selection on size have been measured on juveniles, not adults. Further, parents influence juvenile size by adjusting investment per offspring. In light of these observations, we help resolve this paradox by suggesting that the observed upward selection on size is balanced by selection against investment per offspring, resulting in little or no net selection gradient on size. We find that trade-offs between fecundity and juvenile size are common, consistent with the notion of selection against investment per offspring. We also find that median directional selection on size is positive for juveniles but no net directional selection exists for adult size. This is expected because parent offspring conflict exists over size, and juvenile size is more strongly affected by investment per offspring than adult size. These findings provide qualitative support for the hypothesis that upward selection on size is balanced by selection against investment per offspring, where parent-offspring conflict over size is embodied in the opposing signs of the two selection gradients. PMID- 26283105 TI - Ultrastructure of the ampullary organs of Plicofollis argyropleuron (Siluriformes: Ariidae). AB - The morphology of ampullary organs in Plicofollis argyropleuron, collected from a southeast Queensland estuary, was examined by light and electron microscopy to assess the morphological characteristics of teleost ampullary organs in environments with fluctuating salinities. This catfish possesses both macroampullae and microampullae. Both have the typical teleost arrangement of an ampullary pore linked by a canal to a single ampulla that is lined with receptor and supportive cells. The canal wall of macroampullae consists of a collagen sheath, a basement membrane, and two layers of squamous epithelial cells adjacent to the lumen, joined by desmosomes and tight junctions near the surface of the epithelium. Ampullary pore diameters are similar in range for both the macroampullae and the microampullae, with microampullae always arising from the larger pores within a single region of the head. Canal length of the macroampullae is longer than those of the microampullae. Macroampullae also contain approximately 10 times as many receptor cells compared with the microampullae. In both organs, these pear-shaped receptor cells alternate with supportive cells along the entire luminal surface of the ampulla. The apical region of receptor cells extends into the lumen and bears numerous microvilli. The basal region of receptor cells adjoins to either individual or multiple unmyelinated neural terminals. The coexistence of two markedly different ampullary organ morphologies within a single species support theories concerning the possible multifunctionality of these sensory organs. PMID- 26283106 TI - Balancing Electron Transfer and Surface Passivation in Gradient CdSe/ZnS Core Shell Quantum Dots Attached to ZnO. AB - Core-shell (CS) quantum dots (QDs) are promising light absorbers for solar cell applications mainly because of their enhanced photostability compared with bare QDs. Moreover, the superb photostability can be combined with a low number of defects by using CSQDs with a gradient composition change from the core to the shell. Here, we study electron injection from the gradient CSQDs to ZnO nanoparticles. We observe the typical exponential injection rate dependence on the shell thickness (beta = 0.51 A(-1)) and discuss it in light of previously published results on step-like CSQDs. Despite the rapid drop in injection rates with shell thickness, we find that there exists an optimum thickness of the shell layer at ~1 nm, which combines high injection efficiency (>90%) with a superior passivation of QDs. PMID- 26283108 TI - Porphyrin-Based Supramolecular Nanoarchitectures for Solar Energy Conversion. AB - Photofunctional molecular architectures with well-defined shapes and sizes are of great interest because of various applications such as photovoltaics, photocatalysis, and electronics. Porphyrins are promising building blocks for organized nanoscale superstructures, which perform many of the essential light harvesting and photoinduced electron/energy transfer reaction. In this Perspective, we present the recent advances in supramolecular architectures of porphyrins for solar energy conversion. First, we state preparation and light energy conversion properties of porphyrin (donor: D) and fullerene (acceptor: A) based composite spherical nanoassemblies. The interfacial control of D/A molecules based on our supramolecular strategy successfully demonstrates the drastic enhancement of light energy conversion properties as compared to the corresponding nonorganized systems. Then, bar-shaped structures composed of two different D and A molecules with separated inside and outside layers are discussed. This unusual rod formation shows a possibility for a novel zeolite like photoreaction cavity with efficient visible light absorption. Finally, photophysical and phoelectrochemical properties of supramolecular composites between porphyrins and carbon naotubes/graphenes are briefly described. PMID- 26283107 TI - Activating Carrier Multiplication in PbSe Quantum Dot Solids by Infilling with Atomic Layer Deposition. AB - Carrier multiplication-the generation of multiple electron-hole pairs by a single photon-is currently of great interest for the development of highly efficient photovoltaics. We study the effects of infilling PbSe quantum-dot solids with metal oxides by atomic layer deposition on carrier multiplication. Using time resolved microwave conductivity measurements, we find, for the first time, that carrier multiplication occurs in 1,2-ethanedithiol-linked PbSe quantum-dot solids infilled with Al2O3 or Al2O3/ZnO, while it is negligible or absent in noninfilled films. The carrier-multiplication efficiency of the infilled quantum-dot solids is close to that of solution-dispersed PbSe quantum dots, and not significantly limited by Auger recombination. PMID- 26283109 TI - Exploring the Free Energy Landscape of Solutes Embedded in Lipid Bilayers. AB - Free energy calculations are vital for our understanding of biological processes on an atomistic scale and can offer insight to various mechanisms. However, in some cases, degrees of freedom (DOFs) orthogonal to the reaction coordinate have high energy barriers and/or long equilibration times, which prohibit proper sampling. Here we identify these orthogonal DOFs when studying the transfer of a solute from water to a model membrane. Important DOFs are identified in bulk liquids of different dielectric nature with metadynamics simulations and are used as reaction coordinates for the translocation process, resulting in two- and three-dimensional space of reaction coordinates. The results are in good agreement with experiments and elucidate the pitfalls of using one-dimensional reaction coordinates. The calculations performed here offer the most detailed free energy landscape of solutes embedded in lipid bilayers to date and show that free energy calculations can be used to study complex membrane translocation phenomena. PMID- 26283110 TI - Toward High-Performance Organic-Inorganic Hybrid Solar Cells: Bringing Conjugated Polymers and Inorganic Nanocrystals in Close Contact. AB - Organic-inorganic hybrid solar cells composed of conjugated polymers (CPs) and inorganic nanocrystal (NC) semiconductors have garnered considerable attention as a potential alternative to traditional silicon solar cells due to the capacity of producing high-efficiency solar energy in a cost-effective manner. The combination of advantageous characteristics of CPs and NCs enables the construction of nanostructured high-performance, lightweight, flexible, large area, and low-cost hybrid solar cells. However, it remains a grand challenge to control the film morphology and interfacial structure of such organic/inorganic semiconductor blends on the nanoscale. In this Perspective, we highlight the strategies of implementing close contact between CPs and NCs by tailoring the colloidal synthesis, the coordination reaction, and the chemical modification of CPs. As such, they offer promising opportunities for rationally controlling the phase separation between electron-donating CPs and electron-accepting NCs, increasing the interfacial areas between them, enhancing their electronic interaction, and thus substantially promoting the photovoltaic performance of the resulting organic-inorganic hybrid solar cells. PMID- 26283111 TI - The Role of the Partner Atom and Resonant Excitation Energy in Interatomic Coulombic Decay in Rare Gas Dimers. PMID- 26283112 TI - Organic Solar Cells beyond One Pair of Donor-Acceptor: Ternary Blends and More. AB - Ternary solar cells enjoy both an increased light absorption width, and an easy fabrication process associated with their simple structures. Significant progress has been made for such solar cells with demonstrated efficiencies over 7%; however, their fundamental working principles are still under investigation. This Perspective is intended to offer our insights on the three major governing mechanisms in these intriguing ternary solar cells: charge transfer, energy transfer, and parallel-linkage. Through careful analysis of exemplary cases, we summarize the advantages and limitations of these three major mechanisms and suggest future research directions. For example, incorporating additional singlet fission or upconversion materials into the energy transfer dominant ternary solar cells has the potential to break the theoretical efficiency limit in single junction organic solar cells. Clearly, a feedback loop between fundamental understanding and materials selection is in urgent need to accelerate the efficiency improvement of these ternary solar cells. PMID- 26283113 TI - Traveling through the Desalting Column Spontaneously Transforms Thiolated Ag Nanoclusters from Nonluminescent to Highly Luminescent. AB - This letter reports an unexpected observation in the purification of ultrasmall (<2 nm) thiolate-protected Ag nanoclusters (NCs) via a common separation technique (e.g., desalting column and ultrafiltration), where the nonluminescent Ag NCs were spontaneously transformed to highly luminescent NCs during the separation. This interesting finding was then used to develop a facile and fast (<5 min) synthesis method for highly luminescent Ag NCs. The key strategy was to use the separation process to selectively remove small species (e.g., salts and excess protecting ligands) from the Ag NC solution, which induced a size or structure-focusing of Ag NCs in the solution, leading to the formation of highly luminescent Ag NCs. The concurrent synthesis and purification of highly luminescent Ag NCs via a common "physical separation unit" could be further advanced in a continuous mode for large-scale production of luminescent Ag NCs. PMID- 26283114 TI - Chiral Recognition of l-Gramicidine on Chiraly Methionine-Modified Au(111). AB - A chiral pentadecapeptide, l-gramicidine, has been shown to undergo specific adsorption onto gold surfaces modified by chiral amino acids, d- and l methionine, upon adsorption in the liquid phase. There is a chiral recognition only between the slightly anionic l-peptide and the l-modified surface exhibiting cationic molecules. However, whatever the probe and target molecule charges, very weak recognition was observed between molecules of opposite chirality. PMID- 26283115 TI - Pushing the Envelope of the Intrinsic Limitation of Organic Solar Cells. AB - The photogeneration of Frenkel-type excitons, instead of pairs of free charges, is one of the main drawbacks of organic photovoltaics, when compared with the inorganic counterpart. The strong Coulomb interaction of charge carriers of opposite sign in organic materials is responsible for the complexity of the process of generation of unbound charges, affecting the photogenerated current and still not clearly understood, as well as for the free energy loss of electrons resulting in a diminished open circuit voltage. Despite this practical limitation, record power conversion efficiencies approaching 10% are currently reported for lab-scale single-junction structures made of low-bandgap electron donating conjugated small molecules or polymers blended with electron-accepting fullerene derivatives. To go beyond, a deep understanding of charge generation dynamics, highly system dependent, is necessary for the definition of the rules for the design of high-performance organic materials for the photovoltaic application and possibly the reduction of exciton binding energy, through the increase of the dielectric constant, which definitively would overcome the practical constraints to high efficiency organic solar cells. PMID- 26283116 TI - Tightening and Untying the Knot in Human Carbonic Anhydrase III. AB - The forced mechanical unfolding of the knotted protein Human Carbonic Anhydrase (HCA) III is examined by steered, explicit-water molecular dynamics computer simulations. In agreement with previous indications from experiments and coarse grained simulations, knot tightening by pulling near-terminal amino acids (4 and 267) leads to a much higher resistance to unfolding than for knot untying, where pulling amino acids 4 and 253 untangles the knot by threading the C-terminal end out of the knotting loop. In particular, the resistance during knot tightening is observed to diverge due to a tightly tied-up enzymatic core of the HCA if it is coordinated by the catalytically important zinc ion. The underlying structural pictures are presented and discussed. PMID- 26283117 TI - Redox Chemistry of the Superoxide Ion in a Phosphonium-Based Ionic Liquid in the Presence of Water. AB - Stable electrogenerated superoxide ion has been observed for the first time in a phosphonium-based ionic liquid in the presence of water, leading to a chemically reversible O2/O2(*-) redox couple instead of the disproportionation reaction that is usually observed. It appears that the cation solvates the superoxide anion, stabilizing it against the disproportionation reaction. The electrogeneration is studied at various levels of water or other diluents including toluene to explore the limits of stability of the superoxide ion under these conditions. PMID- 26283118 TI - Controlling Low-Energy Electron Emission via Resonant-Auger-Induced Interatomic Coulombic Decay. AB - We have investigated interatomic Coulombic decay (ICD) after resonant Auger decay in Ar2, ArKr, and ArXe following 2p3/2 -> 4s and 2p3/2 -> 3d excitations in Ar, using momentum-resolved electron-ion-ion coincidence. The results illustrate that ICD induced by the resonant Auger decay is a well-controlled way of producing energy-selected slow electrons at a specific site. PMID- 26283119 TI - Earth-Abundant Cobalt Pyrite (CoS2) Thin Film on Glass as a Robust, High Performance Counter Electrode for Quantum Dot-Sensitized Solar Cells. AB - We report a cobalt pyrite (cobalt disulfide, CoS2) thin film on glass as a robust, high-performance, low-cost, earth-abundant counter electrode for liquid junction quantum dot-sensitized solar cells (QDSSCs) that employ the aqueous sulfide/polysulfide (S(2-)/Sn(2-)) redox electrolyte as the hole-transporting medium. The metallic CoS2 thin film electrode is prepared via thermal sulfidation of a cobalt film deposited on glass and has been characterized by powder X-ray diffraction and electron microscopy. Using the CoS2 counter electrode, CdS/CdSe sensitized QDSSCs display improved short-circuit photocurrent density and fill factor, achieving solar light-to-electricity conversion efficiencies as high as 4.16%, with an average efficiency improvement of 54 (+/-14)% over equivalent devices assembled with a traditional platinum counter electrode. Electrochemical measurements verify that CoS2 shows high electrocatalytic activity toward polysulfide reduction, rationalizing the improved QDSSC performance. CoS2 is also less susceptible to poisoning by the sulfide/polysulfide electrolyte, a problem that plagues platinum electrodes in this application; furthermore, CoS2 exhibits excellent stability in sulfide/polysulfide electrolyte, resulting in highly reproducible performance. PMID- 26283120 TI - Ionization of Nitric Acid on Crystalline Ice: The Role of Defects and Collective Proton Movement. AB - Ionization of nitric acid (HNO3) on a model ice surface is studied using ab initio molecular dynamics at temperatures of 200 and 40 K with a surface slab model that consists of the ideal ice basal plane with locally optimized and annealed defects. Pico- and subpicosecond ionization of nitric acid can be achieved in the defect sites. Key features of the rapid ionization are (a) the efficient solvation of the polyatomic nitrate anion, by stealing hydrogen bonds from the weakened hydrogen bonds at defect sites, (b) formation of contact ion pairs to stable "presolvated" molecular species that are present at the defects, PMID- 26283121 TI - Two-Dimensional Hexagonal Beryllium Sulfide Crystal. AB - We report a new two-dimensional hexagonal beryllium sulfide (h-BeS) sheet with exceptional properties by extensive first-principles calculations. The h-BeS sheet presents an indirect energy gap of 4.26 eV and an outstanding thermodynamic stability up to 1000 K. Armchair-edged nanoribbons of h-BeS are wide-energy-gap semiconductors with a giant Stark effect, while the zigzag-edged ones are metals with spin glass state. Especially, the ferromagnetic zigzag nanoribbons exhibit a net magnetic moment of nearly 1.15 MUB. These interesting electronic and magnetic properties suggest the promise of the h-BeS crystal for potential applications and should inspire experimental enthusiasm. PMID- 26283122 TI - Investigating the Pressure-Induced Amorphization of Zeolitic Imidazolate Framework ZIF-8: Mechanical Instability Due to Shear Mode Softening. AB - We provide the first molecular dynamics study of the mechanical instability that is the cause of pressure-induced amorphization of zeolitic imidazolate framework ZIF-8. By measuring the elastic constants of ZIF-8 up to the amorphization pressure, we show that the crystal-to-amorphous transition is triggered by the mechanical instability of ZIF-8 under compression, due to shear mode softening of the material. No similar softening was observed under temperature increase, explaining the absence of temperature-induced amorphization in ZIF-8. We also demonstrate the large impact of the presence of adsorbate in the pores on the mechanical stability and compressibility of the framework, increasing its shear stability. This first molecular dynamics study of ZIF mechanical properties under variations of pressure, temperature, and pore filling opens the way to a more comprehensive understanding of their mechanical stability, structural transitions, and amorphization. PMID- 26283123 TI - Water Bending Mode at the Water-Vapor Interface Probed by Sum-Frequency Generation Spectroscopy: A Combined Molecular Dynamics Simulation and Experimental Study. AB - We present a combined molecular dynamics simulation and experimental study on the water bending mode at the water-vapor interface using sum-frequency generation (SFG) spectroscopy. The SFG spectrum simulated using an ab initio-based water model shows good agreement with the experimental data. The imaginary part of the SFG response shows a negative peak at ~1650 cm(-1) and a positive peak at ~1730 cm(-1). Our results reveal that these widely (~80 cm(-1)) separated peaks result from the interference of two closely spaced (~29 cm(-1)) peaks of opposite sign. The positive peak at ~1689 cm(-1) originates from water with two donor hydrogen atoms with the HOH angular bisector pointing down toward the bulk, and the negative peak at ~1660 cm(-1) from water with free O-H groups, pointing up. The small frequency difference of 29 cm(-1) indicates that the HOH bending mode frequency of interfacial water is relatively insensitive to the number of hydrogen bonds. PMID- 26283125 TI - Flexible Surface Hopping Approach to Model the Crossover from Hopping to Band like Transport in Organic Crystals. AB - Two distinct pictures are usually evoked when modeling charge transport in organic crystals, that is, band and hopping models, the signature of which is conveyed by a characteristic temperature dependence of mobility. Here, we present a novel flexible surface hopping approach compliant with general Hamiltonians that is able to grasp the crossover from hopping to band-like transport regimes. This approach is applied to solve a one-dimensional mixed quantum-classical model and to calculate the temperature dependence of charge mobility along with the degree of charge spatial localization. It is found that the roles of both local and nonlocal electron-phonon couplings strongly depend on the intrinsic charge localization strength. PMID- 26283124 TI - Investigation of Nanomechanical Properties of beta-Si3N4 Thin Layers in a Prismatic Plane under Tension: A Molecular Dynamics Study. AB - We report molecular dynamics simulations of the nanomechanical properties and fracture mechanisms of beta-Si3N4 thin layers in a prismatic plane under uniaxial tension. It is found that the thin layers in the y loading direction display a linear stress-strain relationship at epsilon < 0.021, and afterward, the stress increases nonlinearly with the strain until fracture occurs. However, for the z direction, the linear response is located at epsilon < 0.051. The calculated fracture stresses and strains of the thin layers increase with strain rates both in both directions. The thin layers exhibit the higher Young's modulus of 0.345 TPa in the z direction, higher than that in the y direction. The origins of crack derive from N(2c-1)-Si and N(6h-1)-Si bonds for the y and z loading directions, respectively. PMID- 26283126 TI - Ultrafast Excited-State Dynamics of ortho-Terphenyl and 1,2-Diphenylcyclohexene: The Role of "Ethylenic Twisting" in the Nonadiabatic Photocyclization of Stilbene Analogs. AB - Nonadiabatic photocyclization is the fundamental step underlying photoswitching and light-assisted bond formation within diarylethylenes, yet the details of the nuclear dynamics leading to cyclization remain unclear. We have examined the ultrafast excited-state dynamics of o-terphenyl (OTP) and 1,2-diphenylcyclohexene (DPCH) in solution to determine how variation in structural constraints impacts the course of nonadiabatic photocyclization specifically in stilbenoids. Measured spectral dynamics reflect cyclization through a S1-to-S0 transition for both systems on picosecond time scales, with excited-state decay appreciably faster for DPCH versus OTP. Supportive ab initio calculations reveal a higher energetic penalty in OTP versus DPCH for reaching the lowest-energy conical intersection from the S1 minimum; this penalty is associated primarily with twisting about the carbon-carbon bond that bridges terminal phenyl groups, a structural change that has a critical role in nonadiabatic cis-trans isomerization of diarylethylenes. Findings provide a new experimental perspective on the elusive nuclear dynamics underlying cis-stilbene photocyclization. PMID- 26283127 TI - Hole Scavenging by Organic Adsorbates on the TiO2 Surface: A DFT Model Study. AB - Understanding the interfacial hole transfer between photoirradiated anatase TiO2 nanoparticles and organic adsorbates at the surface is a crucial step toward the full comprehension and control of the photooxidation processes, which are fundamental in photocatalytic applications for energy production, environmental care, and medical cancer phototherapy. In this density functional study, we use the hybrid functional B3LYP in order to investigate how the hole transfer process takes place at the anatase (101) surface when a series of organic alcohols and acids are adsorbed. The results allow us to propose a mechanism of photoinduced proton dissociation and a scale of scavenging power of the different organic adsorbates (glycerol > tert-butanol > iso-propanol > methanol > formic acid). We observe that the surface dipole originated by the molecular adsorption causes a reduction in the cost to form a hole at a surface oxygen. This can then be trapped by the organic adsorbate only if proton dissociation takes place. In the case of glycerol, the hole transfer triggers further photoinduced chemical reactivity than the simple proton dissociation. Only in the case of cathecol, which is an excellent hole scavenger, the proton dissociation is not a required step. PMID- 26283128 TI - Homogeneous Hydrophobic-Hydrophilic Surface Patterns Enhance Permeation of Nanoparticles through Lipid Membranes. AB - We employ coarse-grained molecular dynamics simulations to understand why certain interaction patterns on the surface of a nanoparticle promote its translocation through a lipid membrane. We demonstrate that switching from a random, heterogeneous distribution of hydrophobic and hydrophilic areas on the surface of a nanoparticle to even, homogeneous patterns substantially flattens the translocation free-energy profile and dramatically enhances permeation. We then proceed to construct a more detailed coarse-grained model of a nanoparticle with flexible hydrophobic and hydrophilic ligands arranged into striped domains. Molecular dynamics simulations of these nanoparticles show that the terminal groups of the ligands tend to arrange themselves into homogeneous patterns, despite the underlying striped domains. These observations are linked to recent experimental studies. PMID- 26283129 TI - Magnet-in-the-Semiconductor Nanomaterials: High Electron Mobility in All Inorganic Arrays of FePt/CdSe and FePt/CdS Core-Shell Heterostructures. AB - We report a colloidal synthesis and electrical and magnetotransport properties of multifunctional "magnet-in-the-semiconductor" nanostructures composed of FePt core and CdSe or CdS shell. Thin films of all-inorganic FePt/CdSe and FePt/CdS core-shell nanostructures capped with In2Se4(2-) molecular chalcogenide (MCC) ligands exhibited n-type charge transport with high field-effect electron mobility of 3.4 and 0.02 cm(2)/V.s, respectively. These nanostructures also showed a negative magnetoresistance characteristic for spin-dependent tunneling. We discuss the mechanism of charge transport and gating in the arrays of metal/semiconductor core-shell nanostructures. PMID- 26283130 TI - Ultrafast Nonradiative Relaxation Channels of Tryptophan. AB - The nonradiative relaxation channels of gas-phase tryptophan excited along the S1 S4 excited states (287-217 nm) have been tracked by femtosecond time-resolved ionization. In the low-energy region, lambda >= 240 nm, the measured transient signals reflect nonadiabatic interactions between the two bright La and Lb states of pipi* character and the dark dissociative pisigma* state of the indole NH. The observed dynamical behavior is interpreted in terms of the ultrafast conversion of the prepared La state, which simultaneously populates the fluorescent Lb> and the dissociative pisigma* states. At higher energies, after excitation of the S4 state, the tryptophan dynamics diverges from that observed in indole, pointing to the opening of a relaxation channel that could involve states of the amino acid part. The work provides a detailed picture of the processes and electronic states involved in the relaxation of the molecule, after photoexcitation in the near part of its UV absorption spectrum. PMID- 26283131 TI - Mapping the Native Conformational Ensemble of Proteins from a Combination of Simulations and Experiments: New Insight into the src-SH3 Domain. AB - The biological function of a protein is strongly tied to the ensemble of three dimensional conformations populated at physiological temperature, and dynamically transforming into each other. Experimental techniques such as nuclear magnetic resonance spectroscopy (NMR) provide a wealth of structural and dynamical information, which, in combination with an accurate atomic-level computational modeling, can disclose the details of protein behavior. We here propose a fast and efficient protocol employing molecular dynamics (MD) simulations and NMR chemical shifts, which allows one to reconstruct the detailed conformational ensemble of small globular proteins. In the case of the well-studied src-SH3 domain, we are able to obtain new important insight including the existence of a helical state in the RT loop and a pathway for single-file water diffusion in and out of the core. PMID- 26283132 TI - Organic Solar Cells-At the Interface. PMID- 26283133 TI - Jumping, Rotating, and Flapping: The Atomic-Scale Motion of Thiophene on Cu(111). AB - Self-assembled monolayers of sulfur-containing heterocycles and linear oligomers containing thiophene groups have been widely employed in organic electronic applications. Here, we investigate the dynamics of isolated thiophene molecules on Cu(111) by combining helium spin-echo (HeSE) spectroscopy with density functional theory calculations. We show that the thiophene/Cu(111) system displays a rich array of aperiodic dynamical phenomena that include jump diffusion between adjacent atop sites over a 59-62 meV barrier and activated rotation around a sulfur-copper anchor, two processes that have been observed previously for related systems. In addition, we present experimental evidence for a new, weakly activated process, the flapping of the molecular ring. Repulsive inter-adsorbate interactions and an exceptionally high friction coefficient of 5 +/- 2 ps(-1) are also observed. These experiments demonstrate the versatility of the HeSE technique, and the quantitative information extracted in a detailed analysis provides an ideal benchmark for state-of-the-art theoretical techniques including nonlocal adsorbate-substrate interactions. PMID- 26283134 TI - DNA/Fusogenic Lipid Nanocarrier Assembly: Millisecond Structural Dynamics. AB - Structural changes occurring on a millisecond time scale during uptake of DNA by cationic lipid nanocarriers are monitored by time-resolved small-angle X-ray scattering (SAXS) coupled to a rapid-mixing stopped-flow technique. Nanoparticles (NPs) of nanochannel organization are formed by PEGylation, hydration, and dispersion of a lipid film of the fusogenic lipid monoolein in a mixture with positively charged (DOMA) and PEGylated (DOPE-PEG2000) amphiphiles and are characterized by the inner cubic structure of very large nanochannels favorable for DNA upload. Ultrafast structural dynamics of complexation and assembly of these cubosome particles with neurotrophic plasmid DNA (pDNA) is revealed thanks to the high brightness of the employed synchrotron X-ray beam. The rate constant of the pDNA/lipid NP complexation is estimated from dynamic roentgenograms recorded at 4 ms time resolution. pDNA upload into the vastly hydrated channels of the cubosome carriers leads to a fast nanoparticle-nanoparticle structural transition and lipoplex formation involving tightly packed pDNA. PMID- 26283135 TI - Application of Reflectron Time-of-Flight Mass Spectroscopy in the Analysis of Astrophysically Relevant Ices Exposed to Ionization Radiation: Methane (CH4) and D4-Methane (CD4) as a Case Study. AB - Methane ices have been detected on ice-coated interstellar grains and on the surface of Kuiper belt objects. These ices are chemically altered by ionizing radiation in the form of energetic photons and charged particles, leading to complex organic molecules. Despite decades of research, the chemical makeup of these newly synthesized molecules has not been completely understood to date. Here, we present a novel application of reflectron time-of-flight mass spectrometry coupled to soft photoionization to probe the molecular formulas of the molecules formed upon interaction of ionizing radiation with simple methane and D4-methane ices. Our study depicts clear evidence of high-molecular-weight hydrocarbons of up to C22, among them alkanes, alkenes, and alkynes/dienes, with those product classes in italics identified for the first time on line and in situ. These studies are particular timely as they provide laboratory data of methane-processed ices, which can be compared to actual data from the New Horizons mission on route to Pluto. PMID- 26283136 TI - Toward Highlighting the Ultrafast Electron Transfer Dynamics at the Optically Dark Sites of Photocatalysts. AB - Building a detailed understanding of the structure-function relationship is a crucial step in the optimization of molecular photocatalysts employed in water splitting schemes. The optically dark nature of their active sites usually prevents a complete mapping of the photoinduced dynamics. In this work, transient X-ray absorption spectroscopy highlights the electronic and geometric changes that affect such a center in a bimetallic model complex. Upon selective excitation of the ruthenium chromophore, the cobalt moiety is reduced through intramolecular electron transfer and undergoes a spin flip accompanied by an average bond elongation of 0.20 +/- 0.03 A. The analysis is supported by simulations based on density functional theory structures (B3LYP*/TZVP) and FEFF 9.0 multiple scattering calculations. More generally, these results exemplify the large potential of the technique for tracking elusive intermediates that impart unique functionalities in photochemical devices. PMID- 26283137 TI - Experimental Correlation Between Interfacial Water Structure and Mineral Reactivity. AB - We present an experimental demonstration of the effect of solvent structure on the interfacial reactivity of the silica/water interface using in situ vibrational Sum-frequency Generation (vSFG) spectroscopy. The response of the molecular arrangement of the interfacial solvent to the presence of cations is pH dependent with the highest sensitivity at neutral pH, relevant to geochemical and biological environments. The pH-dependent changes in vSFG spectra are in excellent correlation with the enhancement of quartz dissolution in salt water, which was hypothesized by Dove et al. to be due to changes of the interfacial solvent structure at the silica surface. vSFG provides mechanistic insights into silica dissolution and sheds light on the role of ions in altering interfacial solvent ordering, which has implications in fields ranging from protein-water interactions to oil recovery. PMID- 26283138 TI - Efficient Electron Collection in Hybrid Polymer Solar Cells: In-Situ-Generated ZnO/Poly(3-hexylthiophene) Scaffolded by a TiO2 Nanorod Array. AB - A nanoarchitectural hybrid polymer solar cell, integrating the ordered and the bulk heterojunction hybrid polymer solar cells, is fabricated by infiltrating the diethylzinc/poly(3-hexylthiophene) (P3HT) solution into the interstices of the TiO2 nanorod (NR) array. An inorganic network composed of tiny ZnO nanocrystals is constructed in the in-situ-generated hybrid within the interstice of the single-crystalline TiO2 NRs. The TiO2 NR array, which possesses a longer electron lifetime and an appropriate electron-transport rate, serves not only as an electron transporter/collector extended from fluorine-doped tin oxide (FTO) electrode to sustain the efficient electron collection but also as a scaffold to hold the sufficient amount of ZnO/P3HT hybrid. The in-situ-generated ZnO/P3HT hybrid layer with superior charge separation efficiency can therefore be thickened in the presence of a TiO2 NR array for increasing the light-harvesting efficiency. A notable efficiency of 2.46% is therefore attained in the TiO2 NR ZnO/P3HT hybrid solar cell. PMID- 26283139 TI - Statistical analysis plan for evaluating low- vs. standard-dose alteplase in the ENhanced Control of Hypertension and Thrombolysis strokE stuDy (ENCHANTED). AB - BACKGROUND: The ENhanced Control of Hypertension And Thrombolysis strokE stuDy trial is a 2 * 2 quasi-factorial active-comparison, prospective, randomized, open, blinded endpoint clinical trial that is evaluating in thrombolysis-eligible acute ischemic stroke patients whether: (1) low-dose (0.6 mg/kg body weight) intravenous alteplase has noninferior efficacy and lower risk of symptomatic intracerebral hemorrhage compared with standard-dose (0.9 mg/kg body weight) intravenous alteplase; and (2) early intensive blood pressure lowering (systolic target 130-140 mmHg) has superior efficacy and lower risk of any intracerebral hemorrhage compared with guideline-recommended blood pressure control (systolic target <180 mmHg). OBJECTIVE: To outline in detail the predetermined statistical analysis plan for the 'alteplase dose arm' of the study. METHODS: All data collected by participating researchers will be reviewed and formally assessed. Information pertaining to the baseline characteristics of patients, their process of care, and the delivery of treatments will be classified, and for each item, appropriate descriptive statistical analyses are planned with appropriate comparisons made between randomized groups. For the trial outcomes, the most appropriate statistical comparisons to be made between groups are planned and described. RESULTS: A statistical analysis plan was developed for the results of the alteplase dose arm of the study that is transparent, available to the public, verifiable, and predetermined before completion of data collection. CONCLUSIONS: We have developed a predetermined statistical analysis plan for the ENhanced Control of Hypertension And Thrombolysis strokE stuDy alteplase dose arm which is to be followed to avoid analysis bias arising from prior knowledge of the study findings. PMID- 26283141 TI - Impact of depression on health utility value in cancer patients. AB - OBJECTIVE: The quality-adjusted life year, which is usually calculated from the health utility value, is now a standard measurement used in political decision making in health. Although depression is the leading cause of decrement in health utility in general population, impact of comorbid depression among cancer patients has not been studied sufficiently. Therefore, this study aimed to measure the impact of depression on cancer patients' health utility score, according to the severity of depression. METHODS: Impact of depression severity (measured by the Patient Health Questionnaire) on health utility score (measured by the EuroQoL-5 scale) was evaluated in a sample of 328 Japanese cancer patients, controlling for performance status, symptom burden, and demographic variables. RESULTS: The patients with depression had significantly lower health utility value than those without depression (mean decrement = 0.14). Decrements in health utility of 0.13, 0.18, and 0.19 were observed for mild, moderate, and moderately severe to severe level of depression, respectively. The difference was significant between groups. Depression severity was a significant predictor for health utility (standardized coefficient beta = -0.25), which was comparable with physical symptom burden and performance status. Participants' age, gender, cancer stage, and comorbid illness were not significant. The model explained 37.9% of the variance. CONCLUSIONS: Even mild level of depression caused clinically meaningful decrement in health utility value in cancer patients, which was comparable with decrements due to major physical complications of cancer. Influence of depression should be carefully investigated when interpreting the quality-adjusted life year among cancer patients. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26283142 TI - The prevalence of migraine in university students: a systematic review and meta analysis. AB - Our aim was to determine the prevalence of migraine amongst university students. Migraine is highly prevalent amongst university students, but the exact frequency remains inconsistent between studies. PubMed, Embase and Google Scholar databases were used to identify studies dealing with the prevalence of migraine amongst university students published between 1 January 1988 and 31 August 2014. The pooled migraine prevalence was calculated using DerSimonian and Laird's random effects model. Heterogeneity of the results was investigated using subgroup analysis and the trend of migraine prevalence according to the publication year and sample size was determined by cumulative analysis. Data were combined from 56 independent studies, analysing a total of 34,904 students. The pooled migraine prevalence was 16.1% [95% confidence interval (CI) 13.6%-18.9%]: 11.3% (95% CI 8.8%-14.4%) amongst male students and 21.7% (95% CI 18.0%-25.8%) amongst female students. Subgroup analysis revealed that diagnostic criteria (P < 0.0001) and gender distribution (P = 0.004) significantly affected migraine prevalence. Cumulative analysis found that the 95% CI became narrower with ascending publication year and sample size. Many studies agree that migraine is highly prevalent amongst university students, but diverse methodologies lead to substantial heterogeneity in the results. It is shown that gender and diagnostic criteria significantly influence the migraine prevalence and may partially explain the heterogeneity between studies. PMID- 26283140 TI - LAP-BAND for BMI 30-40: 5-year health outcomes from the multicenter pivotal study. AB - BACKGROUND: We performed a 5-year multicenter study to evaluate the safety and effectiveness of the LAP-BAND System surgery (LBS) in patients with obesity with a body mass index (BMI) of 30-39.9 kg m(-)(2). This pivotal study was designed to support LBS application to the US Food and Drug Administration for broadening the indications for surgery and the lower BMI indication was approved with 1-year data in 2011, with the intention to complete the 5-year evaluation. OBJECTIVES: To present broad health outcome data including weight change, patient reported outcomes, comorbidity change and complications during the 5-year study. SETTING: The study was conducted at seven US private practice clinical trial sites. METHODS: We enrolled 149 BMI 30-39.9 subjects into a 5-year, multicenter, longitudinal, prospective post-approval study. Data for those completing each time point are presented. RESULTS: The predefined target of at least 30% excess weight loss was achieved by more than 76% of subjects by 1-year and at every year thereafter during the 5-year study. Mean percentage weight loss at 5 years was 15.9+/-12.4%. Sustained weight loss was accompanied by sustained improvement in generic and weight-specific quality of life, symptoms of depression and the prevalence of binge-eating disorder. The number of subjects with normal fasting triglyceride, high-density lipoprotein cholesterol, plasma glucose and HbA1c increased significantly between baseline and 5 years. Fifty-four months after LBS implantation, the rate of device explants without replacement was 5.4%; however, the rate of explants increased to 12.1% by month 60 owing to no cost-elective band removals offered to subjects at study exit. No deaths or unanticipated adverse device effects were reported. CONCLUSIONS: The LBS is safe and effective for people with BMI 30-39.9 with demonstrated improvements in weight loss, comorbidities and quality of life, and with a low explant rate through 5 years following treatment. PMID- 26283143 TI - American Gastroenterological Association Institute Guideline on the Role of Upper Gastrointestinal Biopsy to Evaluate Dyspepsia in the Adult Patient in the Absence of Visible Mucosal Lesions. PMID- 26283144 TI - Direct Measurement of Cardiac Na+ Channel Conformations Reveals Molecular Pathologies of Inherited Mutations. AB - BACKGROUND: Dysregulation of voltage-gated cardiac Na(+) channels (NaV1.5) by inherited mutations, disease-linked remodeling, and drugs causes arrhythmias. The molecular mechanisms whereby the NaV1.5 voltage-sensing domains (VSDs) are perturbed to pathologically or therapeutically modulate Na(+) current (INa) have not been specified. Our aim was to correlate INa kinetics with conformational changes within the 4 (DI-DIV) VSDs to define molecular mechanisms of NaV1.5 modulation. METHOD AND RESULTS: Four NaV1.5 constructs were created to track the voltage-dependent kinetics of conformational changes within each VSD, using voltage-clamp fluorometry. Each VSD displayed unique kinetics, consistent with distinct roles in determining INa. In particular, DIII-VSD deactivation kinetics were modulated by depolarizing pulses with durations in the intermediate time domain that modulates late INa. We then used the DII-VSD construct to probe the molecular pathology of 2 Brugada syndrome mutations (A735V and G752R). A735V shifted DII-VSD voltage dependence to depolarized potentials, whereas G752R significantly slowed DII-VSD kinetics. Both mutations slowed INa activation, although DII-VSD activation occurred at higher potentials (A735V) or at later times (G752R) than ionic current activation, indicating that the DII-VSD allosterically regulates the rate of INa activation and myocyte excitability. CONCLUSIONS: Our results reveal novel mechanisms whereby the NaV1.5 VSDs regulate channel activation and inactivation. The ability to distinguish distinct molecular mechanisms of proximal Brugada syndrome mutations demonstrates the potential of these methods to reveal how inherited mutations, post-translational modifications, and antiarrhythmic drugs alter NaV1.5 at the molecular level. PMID- 26283145 TI - No Benefit of Complex Fractionated Atrial Electrogram Ablation in Addition to Circumferential Pulmonary Vein Ablation and Linear Ablation: Benefit of Complex Ablation Study. AB - BACKGROUND: The optimal ablation strategy for persistent atrial fibrillation (AF) remains unclear. METHODS AND RESULTS: This multicentre randomized study compared circumferential pulmonary vein ablation+linear ablation (control arm) versus circumferential pulmonary vein ablation+linear ablation+complex fractionated atrial electrogram (CFAE) ablation (CFAE arm) in patients with persistent AF. Circumferential pulmonary vein ablation was performed followed by roof and mitral isthmus ablation, before CFAE ablation in the CFAE arm. Ablation strategy was maintained at the first redo procedure. Sixty-five patients were recruited in each arm. The mean age was 61+/-10 years, 75% were men, median AF duration was 2 years, 42% had long-lasting persistent AF, 68% had associated cardiovascular disease, mean left atrial dimension was 46+/-6 mm, and median CHA2DS2-VASc score was 2. Ablation and procedure times were significantly longer in the CFAE arm (70+/-20 versus 55+/-17; 201+/-35 versus 152+/-45 minutes; P<0.005). After a mean follow-up of 35+/-5 months, single-procedural success off antiarrhythmic drugs at 12 months (CFAE: 30/65 [46%] versus control: 37/65 [57%]; P=0.29) and multiprocedural success (CFAE: 51/65 [78%] versus control: 52/65 [80%]; P=1.0) were not significantly different. At the first redo procedure, patients in the CFAE arm had a higher incidence of organized atrial tachycardia/flutter (24/33 [73%] versus 11/31 [35%]; P=0.005) and gap-related macro-re-entrant flutter (8/33[24%] versus 1/31[3%]; P=0.03). Early recurrence of atrial arrhythmia was an independent predictor of late recurrence. CONCLUSIONS: CFAE ablation did not confer incremental benefit when performed in addition to circumferential pulmonary vein ablation and linear ablation. It was associated with a higher incidence of gap-related flutter. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01711047. PMID- 26283146 TI - Presidential Address 2014: The more-or-less interrupting effects of the startle response. AB - The startle response can be used to assess differences in a variety of ongoing processes across species, sensory modalities, ages, clinical conditions, and task conditions. Startle serves defensive functions, but it may also interrupt ongoing processes, allowing for a reorientation of resources to potential danger. A wealth of research suggests that prepulse inhibition of startle (PPI) is an indicator of the protection of the processing of the prepulse from interruption by the startle response. However, protection against interruption by suppressing the startle response may extend to many other ongoing processes, including the higher processing of the startle stimulus itself. Proof of protection would require measuring ongoing processing, which has very rarely been reported. The idea that PPI represents the protection of the earliest stages of prepulse processing can be challenged, since those earliest stages are completed by the time the startle response occurs, so they are not threatened by interruption and need not be protected. The conception of low PPI as indicative of a "gating deficit" in schizophrenia should be made with caution, since low PPI is seen in some, but not all studies of schizophrenia, but also in a range of other disorders and conditions. Finally, startle is often used to probe ongoing processes, but the response also modifies those processes, interrupting some processes but perhaps facilitating others. A deeper understanding of the function of startle and PPI might improve the precision of application of these measures in the investigation of a range of research topics. PMID- 26283148 TI - Transcriptome analysis of grass carp (Ctenopharyngodon idella) fed with animal and plant diets. AB - Numerous studies have been focused on the replacement of fish meal by other alternative protein sources. However, little is currently known about the molecular mechanism of utilization of diets with different protein sources in fish. Grass carp is a typical herbivorous fish. To elucidate the relationship between gene expression and utilization of animal and plant diets, transcriptome sequencing was performed in grass carp fed with chironomid larvae and duckweed. Grass carp fed with duckweed had significantly higher relative length of gut than those fed with chironomid larvae. 4435 differentially expressed genes were identified between grass carp fed with chironomid larvae and duckweed in brain, liver and gut, involved in cell proliferation and differentiation, appetite control, circadian rhythm, digestion and metabolism pathways. These pathways might play important roles in utilization of diets with different protein sources in grass carp. And the findings could provide a new insight into the replacement of fish meal in artificial diets. PMID- 26283147 TI - Models of Intergenerational and Transgenerational Transmission of Risk for Psychopathology in Mice. AB - Trajectories toward risk or resilience in psychiatric disorders are influenced by acquired and inherited factors. More recently, evidence from rodent studies suggest that acquired risk factors can be transmitted through non-genomic, epigenetic mechanisms to subsequent generations, potentially contributing to a cycle of disease and disease risk. Here, we review examples of transmission of environmental factors across generations and illustrate the difference between behavioral transmission and epigenetic inheritance. We highlight essential definitions of intergenerational and transgenerational transmission of disease risk with corresponding examples. We then explore how these phenomena may influence our understanding of psychiatric disorders leading toward new prevention and therapeutic approaches. PMID- 26283149 TI - MMACHC gene mutation in familial hypogonadism with neurological symptoms. AB - Recent studies have convincingly documented that hypogonadism is a component of various hereditary disorders and is often recognized as an important clinical feature in combination with various neurological symptoms, yet, the causative genes in a few related families are still unknown. High-throughput sequencing has become an efficient method to identify causative genes in related complex hereditary disorders. In this study, we performed exome sequencing in a family presenting hypergonadotropic hypogonadism with neurological presentations of mental retardation, epilepsy, ataxia, and leukodystrophy. After bioinformatic analysis and Sanger sequencing validation, we identified compound heterozygous mutations: c.482G>A (p.R161Q) and c.609G>A (p.W203X) in MMACHC gene in this pedigree. MMACHC was previously confirmed to be responsible for methylmalonic aciduria (MMA) combined with homocystinuria, cblC type (cblC disease), a hereditary vitamin B12 metabolic disorder. Biochemical and gas chromatography mass spectrometry (GC-MS) examinations in this pedigree further supported the cblC disease diagnosis. These results indicated that hypergonadotropic hypogonadism may be a novel clinical manifestation of cblC disease, but more reports on additional patients are needed to support this hypothesis. PMID- 26283150 TI - Effects of magnesium degradation products on mesenchymal stem cell fate and osteoblastogenesis. AB - The unique properties of magnesium (Mg) and its alloys that combine favourable mechanical properties, biocompatibility, and biodegradability, which until now have been restricted primarily to polymers, justify its study in the field of implantology. Previous in vivo studies have underlined the possible osteoconductive effects of Mg-based metals, and several in vitro studies have highlighted positive effects of Mg-enriched biomaterials. However, although the observed biological activity of magnesium is intriguing, it remains largely unexplored. Furthermore, due to increased regulations, the introduction of new implants on the market must be accompanied by thorough mechanistic understanding. Therefore, to mimic the in vivo effects of the degradation of Mg-based implants on mesenchymal stem cell differentiation during bone remodelling, non haematopoietic multipotent foetal progenitor cells, i.e., human umbilical cord perivascular cells (HUCPV), were cultured for up to three weeks with or without osteoblastic differentiating media and with or without magnesium extract (approximately 5mM). To partially unveil the mechanism or to select paths for further investigation, a very broad selection of genes was chosen (e.g., those involved in osmolality sensing). Several classical bone markers were also studied at the gene and protein levels. The data suggest that Mg extract alone potentiates cell proliferation or delays the natural fate of maturation/differentiation. However, when the cells are driven toward osteoblastic differentiation, the effect of the Mg extract becomes much more complex, positively or negatively influencing differentiation via various pathways. These preliminary results confirm the choice of the various parameters utilised here and highzlight the importance of further studies. PMID- 26283151 TI - Quality Counts: Developmental Shifts in Associations Between Romantic Relationship Qualities and Psychosocial Adjustment. AB - The present study assessed a developmental task theory of romantic relationships by examining associations between romantic relationship qualities and adjustment across 9 years using a community-based sample of 100 male and 100 female participants (Mage Wave 1 = 15.83) in a Western U.S. city. Using multilevel modeling, the study examined the moderating effect of age on links between romantic relationship qualities and adjustment. Consistent with developmental task theory, high romantic quality was more negatively associated with internalizing symptoms and dating satisfaction during young adulthood than adolescence. Romantic relationship qualities were also associated with externalizing symptoms and substance use, but the degree of association was consistent across ages. The findings underscore the significance of romantic relationship qualities across development. PMID- 26283152 TI - Crouzon Syndrome: Visual Diagnosis. PMID- 26283153 TI - Factors Related to Pump Thrombosis With the Heartmate II Left Ventricular Assist Device. AB - BACKGROUND: Recent reports suggested that HeartMate II (HMII) thrombosis rates may be higher in implants after 2011. We characterize events at HMII centers (>100 HMII implants) whose device thrombosis rates are equivalent or lower than reported by INTERMACS. METHODS: Seven centers pooled implants from 2011 through June 2013 to examine pump thrombus and identify characteristics and clinical strategies that potentially mitigate the risk. A total of 666 patients (age 59 +/ 13 years; 81% male) were studied (support duration: 13.7 +/- 8.3 months, cumulative: 759 patient years). Median target INR was 2.25 (range 2.0 to 2.5), and median pump speed was 9200 rpm (range 8600 to 9600). Pump thrombus was suspected with clinical evidence (e.g., hemolysis, positive ramp test) requiring intervention (e.g., anticoagulation therapy, pump exchange) or patient death. RESULTS: Suspected pump thrombus occurred in 24/666 (3.6%) patients within three months of implant. At six months, 38/666 (5.7%) had suspected pump thrombus including 24 (3.6%) resulting in pump exchange or death. Stroke (hemorrhagic: 0.049, and ischemic: 0.048 events/patient year) and survival (six months: 88 +/- 1%; 1 year: 81 +/- 2%) were consistent with national averages. Suspected pump thrombus patients were younger (55 +/- 13 vs. 59 +/- 13, p = 0.046) and had more females (31.6% vs. 18.3%, p = 0.054). There was no difference in indication, etiology of heart failure, or body size. CONCLUSIONS: This analysis demonstrates low HMII thrombus events. Minimization of risk factors by uniform implant techniques and consistent post-op management may reduce device thrombosis. A larger scale multicenter evaluation may better elucidate the difference in thrombus events between centers. PMID- 26283154 TI - Upregulation of miR-181s reverses mesenchymal transition by targeting KPNA4 in glioblastoma. AB - The goal of this work was to explore the most effective miRNAs affecting glioblastoma multiforme (GBM) phenotype transition and malignant progression. We annotated 491 TCGA samples' miRNA expression profiles according to their mRNA based subtypes and found that the mesenchymal tumors had significantly decreased miR-181 family expression compared with the other three subtypes while the proneural subtype harbored extremely high miR-181 family expression. Patients with high miR-181 family expression had longer overall survival (p = 0.0031). We also confirmed that NF-kappaB-targeting genes and the EMT (epithelial-mesenchymal transition) pathway were inversely correlated with miR-181 family expression and that the entire miR-181 family inhibited glioma cell invasion and proliferation; of these, miR-181b was the most effective suppressor. Furthermore, miR-181b was validated to suppress EMT by targeting KPNA4 and was associated with survival outcome in the TCGA and CGGA datasets and in another independent cohort. The EMT inhibitory effect of miR-181b was lost after KPNA4 expression was restored. We also identified the antitumorigenic activity of miR-181b in vitro and in vivo. Our results showed that miR-181 family expression was closely correlated with TCGA subtypes and patients' overall survival, indicating that miR-181b, a tumor suppressive miRNA, could be a novel therapeutic candidate for treating gliomas. PMID- 26283155 TI - Nucleolin overexpression in breast cancer cell sub-populations with different stem-like phenotype enables targeted intracellular delivery of synergistic drug combination. AB - Breast cancer stem cells (CSC) are thought responsible for tumor growth and relapse, metastization and active evasion to standard chemotherapy. The recognition that CSC may originate from non-stem cancer cells (non-SCC) through plastic epithelial-to-mesenchymal transition turned these into relevant cell targets. Of crucial importance for successful therapeutic intervention is the identification of surface receptors overexpressed in both CSC and non-SCC. Cell surface nucleolin has been described as overexpressed in cancer cells as well as a tumor angiogenic marker. Herein we have addressed the questions on whether nucleolin was a common receptor among breast CSC and non-SCC and whether it could be exploited for targeting purposes. Liposomes functionalized with the nucleolin binding F3 peptide, targeted simultaneously, nucleolin-overexpressing putative breast CSC and non-SCC, which was paralleled by OCT4 and NANOG mRNA levels in cells from triple negative breast cancer (TNBC) origin. In murine embryonic stem cells, both nucleolin mRNA levels and F3 peptide-targeted liposomes cellular association were dependent on the stemness status. An in vivo tumorigenic assay suggested that surface nucleolin overexpression per se, could be associated with the identification of highly tumorigenic TNBC cells. This proposed link between nucleolin expression and the stem-like phenotype in TNBC, enabled 100% cell death mediated by F3 peptide-targeted synergistic drug combination, suggesting the potential to abrogate the plasticity and adaptability associated with CSC and non SCC. Ultimately, nucleolin-specific therapeutic tools capable of simultaneous debulk multiple cellular compartments of the tumor microenvironment may pave the way towards a specific treatment for TNBC patient care. PMID- 26283156 TI - Intranuclear biophotonics by smart design of nuclear-targeting photo-/radio sensitizers co-loaded upconversion nanoparticles. AB - Biophotonic technology that uses light and ionizing radiation for positioned cancer therapy is a holy grail in the field of biomedicine because it can overcome the systemic toxicity and adverse side effects of conventional chemotherapy. However, the existing biophotonic techniques fail to achieve the satisfactory treatment efficacy, which remains a big challenge for clinical implementation. Herein, we develop a novel theranostic technique of "intranuclear biophotonics" by the smart design of a nuclear-targeting biophotonic system based on photo-/radio-sensitizers covalently co-loaded upconversion nanoparticles. These nuclear-targeting biophotonic agents can not only generate a great deal of multiple cytotoxic reactive oxygen species in the nucleus by making full use of NIR/X-ray irradiation, but also produce greatly enhanced intranuclear synergetic radio-/photodynamic therapeutic effects under the magnetic/luminescent bimodal imaging guidance, which may achieve the optimal efficacy in treating radio resistant tumors. We anticipate that the highly effective intranuclear biophotonics will contribute significantly to the development of biophotonic techniques and open new perspectives for a variety of cancer theranostic applications. PMID- 26283157 TI - Use of biomimetic microtissue spheroids and specific growth factor supplementation to improve tenocyte differentiation and adaptation to a collagen based scaffold in vitro. AB - Tenocytes represent a valuable source of cells for the purposes of tendon tissue engineering and regenerative medicine and as such, should possess a high degree of tenogenic differentiation prior to their use in vivo in order to achieve maximal efficacy. In the current report, we identify an efficient means by which to maintain differentiated tenocytes in vitro by employing the hanging drop technique in combination with defined growth media supplements. Equine tenocytes retained a more differentiated state when cultured as scaffold-free microtissue spheroids in low serum-containing medium supplemented with L-ascorbic acid 2 phosphate, insulin and transforming growth factor (TGF)-beta1. This was made evident by significant increases in the expression levels of pro-tenogenic markers collagen type I (COL1A2), collagen type III (COL3A1), scleraxis (SCX) and tenomodulin (TNMD), as well as by enhanced levels of collagen type I and tenomodulin protein. Furthermore, tenocytes cultured under these conditions demonstrated a typical spindle-like morphology and when embedded in collagen gels, became highly aligned with respect to the orientation of the collagen structure following their migration out from the microtissue spheroids. Our findings therefore provide evidence to support the use of a biomimetic microtissue approach to culturing tenocytes and that in combination with the defined growth media described, can improve their differentiation status and functional repopulation of collagen matrix. PMID- 26283158 TI - Enabling non-invasive assessment of an engineered endothelium on ePTFE vascular grafts without increasing oxidative stress. AB - Magnetic resonance imaging (MRI) in combination with contrast enhancement is a potentially powerful tool to non-invasively monitor cell distribution in tissue engineering and regenerative medicine. The most commonly used contrast agent for cell labeling is super paramagnetic iron oxide nanoparticles (SPIONs). However, uptake of SPIONs triggers the production of reactive oxygen species (ROS) in cells often leading to a pro-inflammatory phenotype. The objective of this study was to develop a labeling system to non-invasively visualize an engineered endothelium in vascular grafts without creating excessive oxidative stress. Specifically, we investigated: (1) chitosan-coated SPIONs (CSPIONs) as an antioxidant contrast agent for contrast enhancement, and (2) poly(1,8 octamethylene citrate) (POC) as an antioxidant interface to support cell adhesion and function of labeled cells on the vascular graft. While SPION-labeled endothelial cells (ECs) experienced elevated ROS formation and altered cell morphology, CSPION-labeled ECs cultured on POC-coated surfaces mitigated SPION induced ROS formation and maintained EC morphology, phenotype, viability and functions. A monolayer of labeled ECs exhibited sufficient contrast with T2 weighed MR imaging. CSPION labeling of endothelial cells in combination with coating the graft wall with POC allows non-invasive monitoring of an engineered endothelium on ePTFE grafts without increasing oxidative stress. PMID- 26283159 TI - Cell type-specific adaptation of cellular and nuclear volume in micro-engineered 3D environments. AB - Bio-functionalized three-dimensional (3D) structures fabricated by direct laser writing (DLW) are structurally and mechanically well-defined and ideal for systematically investigating the influence of three-dimensionality and substrate stiffness on cell behavior. Here, we show that different fibroblast-like and epithelial cell lines maintain normal proliferation rates and form functional cell-matrix contacts in DLW-fabricated 3D scaffolds of different mechanics and geometry. Furthermore, the molecular composition of cell-matrix contacts forming in these 3D micro-environments and under conventional 2D culture conditions is identical, based on the analysis of several marker proteins (paxillin, phospho paxillin, phospho-focal adhesion kinase, vinculin, beta1-integrin). However, fibroblast-like and epithelial cells differ markedly in the way they adapt their total cell and nuclear volumes in 3D environments. While fibroblast-like cell lines display significantly increased cell and nuclear volumes in 3D substrates compared to 2D substrates, epithelial cells retain similar cell and nuclear volumes in 2D and 3D environments. Despite differential cell volume regulation between fibroblasts and epithelial cells in 3D environments, the nucleus-to-cell (N/C) volume ratios remain constant for all cell types and culture conditions. Thus, changes in cell and nuclear volume during the transition from 2D to 3D environments are strongly cell type-dependent, but independent of scaffold stiffness, while cells maintain the N/C ratio regardless of culture conditions. PMID- 26283160 TI - Modulation of inflammation and angiogenesis and changes in ECM GAG-activity via dual delivery of nucleic acids. AB - Tissue-engineered organs and implants hold promise for the replacement of damaged and diseased organs. However, the foreign body response (FBR) is a major obstacle that compromises the function of tissue-engineered constructs, typically causing them to fail. Two components of FBR are an inflammatory response and a lack of vascularization. To overcome these limitations, a collagen system was developed to release interleukin-6 (IL-6) siRNA and endothelial nitric oxide synthase (eNOS) pDNA in a staggered manner. Hollow collagen microspheres were assembled into a collagen sphere-in-hydrogel system that displayed a staggered release profile in vitro. This system was assessed in vivo in a subcutaneous rat model. The doses of IL-6 siRNA and eNOS pDNA were first individually optimized for their ability to reduce the volume fraction of inflammatory cells (7 days) and increase the length density of blood vessels (14 days), respectively. The identified optimal doses were combined, and the ability of the system to decrease the volume fraction of inflammatory cells and increase the length density of blood vessels was confirmed at both 7 and 14 days. Analysis of the tissue using Raman microspectroscopy revealed that in addition to changes in inflammation and angiogenesis, there were also changes in the extracellular matrix (ECM) at seven days. While changes in sulfated glycosaminoglycan (sGAG) content of the ECM were not detected, changes in the binding of sGAG of the ECM to growth factors were observed. Two growth factors tested, VEGF165 and bFGF showed increased binding to sGAG extracted from eNOS pDNA-treated samples at seven days, increasing the angiogenic potential of the ECM. Thus, we observe that changes in the tissue in terms of the balance of inflammation and angiogenesis as well changes in the activity of sGAG of the ECM occurs following dual delivery of nucleic acids from the collagen sphere-in-hydrogel system. PMID- 26283161 TI - [Medication errors related to computerized physician order entry at the hospital: Record and analysis over a period of 4 years]. AB - OBJECTIVES: Computerized physician order entry (CPOE) can generate medication errors. It is necessary to identify them and analyse their causes in order to secure the medication use system. METHODS: Errors were recorded during the pharmaceutical analysis of prescriptions over a period of 4 years on 425 beds. A code frame was provided. Errors were classified according to type, causes and time of detection. The most often drug implicated and the error correction rate were studied. Deep causes were determined and contributing factors were listed. RESULTS: Among 99,536 prescriptions analyzed, 2636 errors were detected (2.65 errors per 100 orders analyzed). The most common error was omission (31.49%). The most represented cause was redundancy requirement (11.34%). Antibacterials were most commonly involved (224 errors). Exactly 65.9% of the prescriptions were modified by physicians. Three root causes were identified: (1) configuration issues; (2) misuse; (3) design problem. Three types of contributing factors have also been detailed: economic, human and technical factors. CONCLUSIONS: Identifying root causes has targeted three types of improvement actions: (1) software settings; (2) training of users; (3) requests for improvements. Contributing factors have to be identified to control the generated risk. Some errors related to CPOE may lead to serious side effects for the patient. That is why it is necessary to identify these errors and analyze them in order to implement improvement actions and prevention to secure the prescription. PMID- 26283162 TI - Single-incision laparoscopic surgery for diverticulitis in overweight patients. AB - AIM: Single-incision laparoscopic surgery (SILS) has been introduced as a new technique for the treatment of various colorectal diseases. Recurrent or complicated diverticulitis of the sigmoid colon is a frequent indication for minimally invasive sigmoid colectomy. The aim of this study was to investigate the impact of obesity on the outcome of SILS sigmoid colectomy. METHODS: From September 2009 to October 2014, data from 377 patients who had intended SILS sigmoid colectomy for diverticulitis at our institution were collected in a prospective database. The patients were categorized in the following subgroups: group 1 (normal weight, body mass index (BMI) < 25 kg/m(2)), group 2 (overweight, BMI 25-29.9 kg/m(2)), group 3 (obesity, BMI 30-34.9 kg/m(2)), and group 4 (morbid obesity, BMI > 35 kg/m(2)). RESULTS: The groups were equivalent for sex, age, status of diverticulitis, the presence of acute inflammation in the specimen, and the percentage of teaching operations, but the percentage of patients with accompanying diseases was significantly more frequent in groups 2, 3, and 4 (p = 0.04, 0.008, and 0.018, respectively). As compared to group 1, the conversion rate was significantly increased in groups 2 and 4 (2.3 vs. 9.3% (p = 0.013) and 2.3 vs. 12.5% (p = 0.017), respectively). The duration of surgery, hospitalization, and morbidity did not differ between the four groups. CONCLUSION: Up to a body mass index of 35 kg/m(2), increased body weight does not significantly reduce the feasibility and outcome of single-incision laparoscopic surgery for diverticulitis. PMID- 26283163 TI - Direct comparison of current cell-based and cell-free approaches towards the repair of craniofacial bone defects - A preclinical study. AB - For craniofacial bone defect repair, several alternatives to bone graft (BG) exist, including the combination of biphasic calcium phosphate (BCP) biomaterials with total bone marrow (TBM) and bone marrow-derived mesenchymal stromal cells (MSCs), or the use of growth factors like recombinant human bone morphogenic protein-2 (RhBMP-2) and various scaffolds. Therefore, clinicians might be unsure as to which approach will offer their patients the most benefit. Here, we aimed to compare different clinically relevant bone tissue engineering methods in an "all-in-one" study in rat calvarial defects. TBM, and MSCs committed or not, and cultured in two- or three-dimensions were mixed with BCP and implanted in bilateral parietal bone defects in rats. RhBMP-2 and BG were used as positive controls. After 7 weeks, significant de novo bone formation was observed in rhBMP 2 and BG groups, and in a lesser amount, when BCP biomaterials were mixed with TBM or committed MSCs cultured in three-dimensions. Due to the efficacy and safety of the TBM/BCP combination approach, we recommend this one-step procedure for further clinical investigation. STATEMENT OF SIGNIFICANCE: For craniofacial repair, total bone marrow (BM) and BM mesenchymal stem cell (MSC)-based regenerative medicine have shown to be promising in alternative to bone grafting (BG). Therefore, clinicians might be unsure as to which approach will offer the most benefit. Here, BM and MSCs committed or not were mixed with calcium phosphate ceramics (CaP) and implanted in bone defects in rats. RhBMP-2 and BG were used as positive controls. After 7 weeks, significant bone formation was observed in rhBMP-2 and BG groups, and when CaP were mixed with BM or committed MSCs. Since the BM-based procedure does not require bone harvest or cell culture, but provides de novo bone formation, we recommend consideration of this strategy for craniofacial applications. PMID- 26283164 TI - Porous nanofibrous poly(L-lactic acid) scaffolds supporting cardiovascular progenitor cells for cardiac tissue engineering. AB - Myocardial infarction (MI) is the irreversible necrosis of heart with approximately 1.5 million cases every year in the United States. Tissue engineering offers a promising strategy for cardiac repair after MI. However, the optimal cell source for heart tissue regeneration and the ideal scaffolds to support cell survival, differentiation, and integration, remain to be developed. To address these issues, we developed the technology to induce cardiovascular progenitor cells (CPCs) derived from mouse embryonic stem cells (ESCs) towards desired cardiomyocytes as well as smooth muscle cells and endothelial cells. We fabricated extracellular matrix (ECM)-mimicking nanofibrous poly(l-lactic acid) (PLLA) scaffolds with porous structure of high interconnection for cardiac tissue formation. The CPCs were seeded into the scaffolds to engineer cardiac constructs in vitro. Fluorescence staining and RT-PCR assay showed that the scaffolds facilitated cell attachment, extension, and differentiation. Subcutaneous implantation of the cell/scaffold constructs in a nude mouse model showed that the scaffolds favorably supported survival of the grafted cells and their commitment to the three desired lineages in vivo. Thus, our study suggested that the porous nanofibrous PLLA scaffolds support cardiac tissue formation from CPCs. The integration of CPCs with the nanofibrous PLLA scaffolds represents a promising tissue engineering strategy for cardiac repair. STATEMENT OF SIGNIFICANCE: Myocardial infarction is the irreversible necrosis of heart with approximately 1.5 million cases every year in the United States. Tissue engineering offers a promising strategy for cardiac repair after MI. However, the optimal cell source for heart tissue regeneration and the ideal scaffolds to support cell survival, differentiation, and integration, remain to be developed. To address these issues, we developed porous nanofibrous PLLA scaffolds that mimic natural extracellular matrix to support cardiac tissue formation from CPCs. The integration of CPCs with the nanofibrous PLLA scaffolds represents a promising tissue engineering strategy for cardiac repair. PMID- 26283166 TI - Microstructures, mechanical properties and cytotoxicity of low cost beta Ti-Mn alloys for biomedical applications. AB - The microstructures, mechanical properties and biocompatibility of low cost beta type Ti-(6-18)Mn alloys were investigated after solution treatment. Ti-9 Mn exhibits the best combination of tensile strength and elongation among the fabricated alloys, and its performance is comparable to or superior to those of Ti-6Al-4V ELI (Ti-64 ELI) in terms of every parameter evaluated. A hardness of 338 HV, a Young's modulus of 94 GPa, a 0.2% proof stress of 1023 MPa, an ultimate tensile strength of 1048 MPa and elongation of 19% were obtained for Ti-9 Mn. Furthermore, the cell viability and metallic ion release ratios are comparable to those of commercially pure titanium, making this alloy promising for biomedical applications. The Young's modulus is also lower than that of Ti-64 ELI (110 GPa), which can possibly reduce the stress shielding effect in implanted patients. STATEMENT OF SIGNIFICANCE: This study evaluates mechanical and biological performance of low cost solution treated beta-type Ti-(6, 9, 13 and 18 mass%)Mn alloys. It includes alloys containing a Mn content range higher than most previously published works (which is around or lower than 8 mass%). Furthermore, the effects of the omega phase and the beta phase stability of the alloys over some mechanical properties and microstructures are discussed. Ion release behavior under simulated body fluids and cell viability are also evaluated. For the case of the Ti-9 Mn, a mechanical and biological performance that is comparable to or superior than that of the widely used Ti-6Al-4V ELI and commercially pure Ti was observed. PMID- 26283165 TI - Engineered composite fascia for stem cell therapy in tissue repair applications. AB - A critical challenge in tissue regeneration is to develop constructs that effectively integrate with the host tissue. Here, we describe a composite, laser micromachined, collagen-alginate construct containing human mesenchymal stem cells (hMSCs) for tissue repair applications. Collagen type I was fashioned into laminated collagen sheets to form a mechanically robust fascia that was subsequently laser micropatterned with pores of defined dimension and spatial distribution as a means to modulate mechanical behavior and promote tissue integration. Significantly, laser micromachined patterned constructs displayed both substantially greater compliance and suture retention strength than non patterned constructs. hMSCs were loaded in an RGD-functionalized alginate gel modified to degrade in vivo. Over a 7 day observation period in vitro, high cell viability was observed with constant levels of VEGF, PDGF-beta and MCP-1 protein expression. In a full thickness abdominal wall defect model, the composite construct prevented hernia recurrence in Wistar rats over an 8-week period with de novo tissue and vascular network formation and the absence of adhesions to underlying abdominal viscera. As compared to acellular constructs, constructs containing hMSCs displayed greater integration strength (cell seeded: 0.92 +/- 0.19 N/mm vs. acellular: 0.59 +/- 0.25 N/mm, p=0.01), increased vascularization (cell seeded: 2.7-2.1/hpf vs. acellular: 1.7-2.1/hpf, p<0.03), and increased infiltration of macrophages (cell seeded: 2021-3630 MUm(2)/hpf vs. acellular: 1570-2530 MUm(2)/hpf, p<0.05). A decrease in the ratio of M1 macrophages to total macrophages was also observed in hMSC-populated samples. Laser micromachined collagen-alginate composites containing hMSCs can be used to bridge soft tissue defects with the capacity for enhanced tissue repair and integration. STATEMENT OF SIGNIFICANCE: Effective restoration of large soft tissue defects caused by trauma or treatment complications represents a critical challenge in the clinic. In this study, a novel composite construct was engineered and evaluated for stem cell delivery and tissue repair. Laser micromachining was used to fabricate patterned, microporous constructs designed with pores of defined size and distribution as a means to tune mechanical responses, accommodate and protect incorporated cells, and enhance tissue integration. The construct was embedded within an engineered alginate gel containing hMSCs. Upon repair of a full thickness abdominal wall defect in a rat model, the composite construct modulated host innate immunity towards a reparative phenotypic response, promoted neovascularization and associated matrix production, and increased the strength of tissue integration. PMID- 26283167 TI - Porphine functionalized nanoparticles of star-shaped poly(epsilon-caprolactone)-b D-alpha-tocopheryl polyethylene glycol 1000 succinate biodegradable copolymer for chemophotodynamic therapy on cervical cancer. AB - We developed a system of biodegradable nanoparticles (NPs) of 5,10,15,20 tetrakis(4-aminophenyl)-21H,23H-porphine (TAPP) centered, 4 arm star-shaped copolymers based on poly(epsilon-caprolactone) (PCL) and D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) for combinatory chemophotodynamic therapy by using docetaxel (DTX) as a model anticancer drug and TAPP as photodynamic sensitizer. TPGS component in the copolymer plays an important role in enhancing the drug encapsulation efficiency, drug release kinetics and cellular uptake of the NPs, as well as in overcoming the multidrug resistance due to inhibition of P-glycoproteins (P-gp) of the cancer cells. We demonstrated in vitro by using the MCF7/ADR breast cancer cells of P-gp overexpression and the HeLa cervical cancer cells that the proposed chemophotodynamic therapy by the DTX loaded TAPP-PCL-b-TPGS NPs could have much higher therapeutic effect than the original drug Taxotere(r). IC50 data showed that the DTX-loaded TAPP-PCL-b-TPGS NPs chemophotodynamic therapy could be 9.36 and 56.5-fold efficient after 24 and 48h treatment, respectively in comparison with the Taxotere(r) chemotherapy. The in vivo investigation by employing a cervical cancer xenograft model further confirmed the advantages of the proposed chemophotodynamic therapy by the DTX loaded TAPP-PCL-b-TPGS NPs versus the Taxotere(r) chemotherapy. PMID- 26283168 TI - The impact of oral health on daily performances and its association with clinical variables in a population in Zambia. AB - OBJECTIVE: The aim of this study was to investigate oral impacts on daily performance and to relate these data to oral clinical variables. MATERIAL AND METHODS: The study was performed at a dental clinic in Livingstone, Zambia, and included 78 subjects (mean age 28, range 15-48 years) consecutively recruited in connection with a dental care visit. Data were collected through a structured interview using the Oral Impacts on Daily Performances (OIDP) index measuring oral health-related quality of life followed by a clinical examination. RESULTS: Oral health affected one or more daily performances during the last 6 months for 61.5% of the subjects. 'Difficulty of eating and enjoying food' was the performance reported most frequently (42.3%), and 'speaking and pronouncing clearly' was least often reported (10.3%). DMFT was 3.8, +/-3.6 (mean +/- SD; range 0-15). A majority of the individuals had periodontal pockets >=4 mm (mean 4.3, +/-2.6) (94.9%) and gingival bleeding on probing >20% (88.5%). Two or more decayed teeth were shown to be significantly associated (OR 4.6, CI 1.2-17.1) with one or more oral impacts on daily performances in a multivariate logistic regression analysis. CONCLUSIONS: This study shown that there is a significant association between decayed teeth and oral impacts on daily performances. More research is needed, however, for deeper understanding of oral health problems and their impacts on daily life in Zambia. PMID- 26283169 TI - A modified thymosin alpha 1 inhibits the growth of breast cancer both in vitro and in vivo: suppressment of cell proliferation, inducible cell apoptosis and enhancement of targeted anticancer effects. AB - Thymosin alpha 1 (Talpha1) is commonly used for treating several diseases; however its usage has been limited because of poor penetration of the target tissue, such as tumor cells. In the present study, Talpha1-iRGD, a peptide by conjugating Talpha1 with the iRGD fragment, was evaluated its performance in MCF 7 and MDA-MB-231 human breast cancer cells. Compared with the wild-type peptide, Talpha1-iRGD was more selective in binding tumor cells in the cell attachment assay. Furthermore, the MTT assay confirmed that Talpha1-iRGD proved more effective in significantly inhibiting the growth of MCF-7 cells in contrast to the general inhibition displayed by Talpha1. Further, conjugation of Talpha1 with iRGD preserved the immunomodulatory activity of the drug by increasing the proliferation of mouse spleen lymphocytes. Further, compared with Talpha1 treatment, Talpha1-iRGD treatment of MCF-7 cells considerably increased the number of cells undergoing apoptosis, resulting in a dose-dependent inhibition of cancer cell growth, which was associated with a much better effect on up regulation of the expression of BCL2-associated X protein (Bax), caspase 9, etc. More importantly, treatment with Ta1-iRGD was more efficacious than treatment with Ta1 in vivo. This study highlights the importance of iRGD on enhancement of cell penetration and tumor accumulation. In summary, our findings demonstrate that the novel modified Talpha1 developed in this study has the potential to be used for treating breast cancer. PMID- 26283170 TI - In vitro antiproliferative, pro-apoptotic, antimetastatic and anti-inflammatory potential of 2,4-diacetylphloroglucinol (DAPG) by Pseudomonas aeruginosa strain FP10. AB - The 2,4-diacetylphloroglucinol (DAPG), a polyketide metabolite extracted from Pseudomonas aeruginosa strain FP10, exhibited selective cytoxicity against lung (A549), breast (MDA MB-231), cervical (HeLa) and colon (HCT-15) cancer cells in differential and dose-dependent manner. The anticancer and antimetastatic activities of DAPG were mediated by the inhibition of ROS, NF-kappaB, Bcl-2, MMP 2, VEGF and primary inflammatory mediators such as TNF-alpha, IL-6, IL-1beta and NO. The DAPG induced apoptosis in cancer cells by intrinsic and extrinsic pathways via the release of cytochrome-C, upregulation of Bax and the activation of caspases and also, exhibited anti-inflammatory activity by the inhibition of LPS-inflammed cell proliferation of macrophage (Raw 264.7), monocytic cells (THP 1) and peripheral blood mononuclear cells (PBMCs). Results further confirmed that the DAPG inhibited the primary inflammatory mediators in cancer cells and inflammed immune cells through the down regulation of NF-kappaB. In the present study, for the first time, antiproliferative, proapoptotic, antimetastatic and anti-inflammatory activities of DAPG in various cancer cells and inflammation induced immune cells have been reported. PMID- 26283171 TI - Effect of Caesalpinia sappan L. extract on physico-chemical properties of emulsion-type pork sausage during cold storage. AB - This study was performed to investigate the effect of extract from heart wood of Caesalpinia sappan on the physico-chemical properties and to find the appropriate addition level in the emulsion-type pork sausage during cold storage. The pH of treatments with C. sappan extract was significantly lower than control and T1 during cold storage periods (P<0.05). Also, the reduction of moisture content, and the increase of cooking loss significantly occurred by the addition of 0.2% C. sappan extract. Also, the texture properties and sensory of sausages containing C. sappan extract were decreased compared to control. Inclusion of the C. sappan extract in sausages resulted in lower lightness and higher yellowness, chroma and hue values. However, the antioxidant, antimicrobial activity, and volatile basic nitrogen in the emulsion-type pork sausages with C. sappan extract showed increased quality characteristics during cold storage. In conclusion, the proper addition level of C. sappan extract was 0.1% on the processing of emulsion type pork sausage. PMID- 26283172 TI - Characterization of MHC class II B polymorphism in multiple populations of wild gorillas using non-invasive samples and next-generation sequencing. AB - Genes encoded by the major histocompatibility complex (MHC) are crucial for the recognition and presentation of antigens to the immune system. In contrast to their closest relatives, chimpanzees and humans, much less is known about variation in gorillas at these loci. This study explored the exon 2 variation of DPB1, -DQB1, and -DRB genes in 46 gorillas from four populations while simultaneously evaluating the feasibility of using fecal samples for high throughput MHC genotyping. By applying strict similarity- and frequency-based analysis, we found, despite our modest sample size, a total of 18 alleles that have not been described previously, thereby illustrating the potential for efficient and highly accurate MHC genotyping from non-invasive DNA samples. We emphasize the importance of controlling for multiple potential sources of error when applying this massively parallel short-read sequencing technology to PCR products generated from low concentration DNA extracts. We observed pronounced differences in MHC variation between species, subspecies and populations that are consistent with both the ancient and recent demographic histories experienced by gorillas. PMID- 26283173 TI - Role of the tumor necrosis factor receptor-associated factor-type zinc finger domain containing protein 1 (TRAFD1) from the hard tick Haemaphysalis longicornis in immunity against bacterial infection. AB - A tumor necrosis factor receptor-associated factor-type zinc finger domain containing protein 1 (TRAFD1) is a negative feedback regulator that controls excessive immune responses in vertebrates. The sequence of tick hemolymph TRAFD1 from the hard tick Haemaphysalis longicornis (HlTRAFD1) was analyzed after identification and cloning from the expressed sequence tag database. RT-PCR and Western blot analyses showed that HlTRAFD1 transcript and protein levels after blood feeding were present in all developmental stages, and the transcript level was consistently high in all organs examined from adult female ticks upon engorgement. Knockdown of HlTRAFD1 gene by RNA interference did not affect blood feeding or oviposition. However, HlTRAFD1 silencing affected the expression of the longicin gene, a defensin-like molecule, but not the lysozyme gene. Moreover, the survival rate of HlTRAFD1-silenced ticks was lower, and the number of E. coli was higher in the hemolymph and plasmatocytes after E. coli injection compared to the control group. These results suggested that HlTRAFD1 strongly affected both the humoral and cellular immunity of ticks. PMID- 26283174 TI - Quantification of viral genome in cord blood donors by real time PCR to investigate human herpesvirus type 8 active infection. AB - Umbilical cord blood (UCB) is one of the most important sources of hematopoietic stem cells which can be used for transplantation. The transplanted CB stem cells might cause infections in recipients. The aim of this study is to evaluate Human Herpes Virus8 (HHV8) as a Rhadinovirus among CB samples in order to assess safety of cord blood stem cells transplantation. To assess this aim, we surveyed 800 cord blood specimens by Real Time PCR.The overall HHV8 incidence in cord blood mononuclear cells was 1.38% and none of them was in lytic phase of HHV8. The authors suggest further HHV8 study on CB samples for transplantation. PMID- 26283175 TI - Effectiveness of the haemonetics MCS cell separator in the collection of apheresis platelets. AB - Platelet (PLT) transfusions play an important role in patients with thrombocytopenia or severely impaired platelet function. Platelet concentrates are prepared from whole-blood donations or by plateletpheresis. In recent years, different instruments have been developed to perform plateletpheresis. We evaluated an apheresis instrument, the Haemonetics MCS((r)) + with regard to PLT yield, collection efficiency (CE), and collection rate (CR) in a retrospective, randomized study in 526 donors. In this system, we used leukoreduction filters post collection to obtain leukoreduced products. The Haemonetics MCS((r)) + cell separator efficiently collected apheresis platelets with median PLT yields of 3.7 * 10(11), mean CE of 66.69 +/- 13.73% and mean CR of 0.063 +/- 0.013 * 10(11)/min. The median blood volume processed was 3290 (2420-4370) ml, and the median volume of acid citrate dextrose-A (ACD-A) used in collections on the device was 385 (196-517) ml. Also, this device allowed the collection of white blood cell (WBC) reduced plateletpheresis with mean 0.07 +/- 0.15 * 10(6) WBC content. No serious donor or recipient reactions occurred. PMID- 26283176 TI - Plasma-exchange as a "rescue therapy" for dermato/polymyositis in acute phase. Experience in three young patients. AB - There are few data in the literature supporting the efficacy of plasma-exchange in dermato/polymyositis. The authors report three cases of patients with acute disease phase showing severe pharyngo-esophageal muscle weakness unresponsive to conventional therapy (corticosteroids and immunosuppressant agents) who were treated with plasma-exchange. As the patients were at high risk of "aspiration pneumonia", tracheostomy and PEG tubes were placed. The patients underwent a series of plasma-exchange for a mean of 15 weeks, during which time they progressively recovered muscle strength, their serum muscle enzyme values returned to normal levels, and MRI showed resolution of muscle edema. The tracheostomy and PEG tubes could be removed. Our findings suggest that plasma exchange in association with immunosuppressant agents could play a relevant role in the management of dermato/polymyositis in acute phase. PMID- 26283177 TI - Association Between the 4p16 Susceptibility Locus and the Risk of Atrial Septal Defect in Population from Southeast China. AB - Three single nucleotide polymorphisms (SNPs), rs16835979, rs870142 and rs6824295, located in chromosome 4p16 were associated with the risk of ostium secundum atrial septal defect (ASD) in the European population. The 4p16 susceptibility locus in congenital heart disease was replicated in Chinese populations. Here, we analyzed the associations between these three SNPs and ASD in Chinese population from Fujian Province in southeast China. We conducted a case-control study by genotyping three SNPs in 354 non-syndromic ASD patients and 557 non-CHD control subjects. Logistic regression analyses showed that the genotype and allele frequencies of these three SNPs were significantly different between the cases and controls in Fujian Chinese population. The allele A of rs870142, the allele A of rs16835979 and the allele A of rs6824295 were significantly associated with an increased risk of ASD. According to the analysis of the three SNPs, the haplotype of AAA was associated with a significantly increased risk of ASD. Our study further supports that these three SNPs confer the predisposition to ASD phenotype in Chinese population. PMID- 26283178 TI - MVDA: a multi-view genomic data integration methodology. AB - BACKGROUND: Multiple high-throughput molecular profiling by omics technologies can be collected for the same individuals. Combining these data, rather than exploiting them separately, can significantly increase the power of clinically relevant patients subclassifications. RESULTS: We propose a multi-view approach in which the information from different data layers (views) is integrated at the levels of the results of each single view clustering iterations. It works by factorizing the membership matrices in a late integration manner. We evaluated the effectiveness and the performance of our method on six multi-view cancer datasets. In all the cases, we found patient sub-classes with statistical significance, identifying novel sub-groups previously not emphasized in literature. Our method performed better as compared to other multi-view clustering algorithms and, unlike other existing methods, it is able to quantify the contribution of single views on the final results. CONCLUSION: Our observations suggest that integration of prior information with genomic features in the subtyping analysis is an effective strategy in identifying disease subgroups. The methodology is implemented in R and the source code is available online at http://neuronelab.unisa.it/a-multi-view-genomic-data-integration methodology/ . PMID- 26283180 TI - Angular roughshark Oxynotus centrina (Squaliformes: Oxynotidae) in captivity feeding exclusively on elasmobranch eggs: an overlooked feeding niche or a matter of individual taste? AB - A specimen of angular roughshark Oxynotus centrina has been kept successfully in captivity for the first time. Over a period of 24 months, the specimen preyed exclusively on the contents of elasmobranch egg cases, suggesting a specialized trophic niche. PMID- 26283179 TI - OLA1 regulates protein synthesis and integrated stress response by inhibiting eIF2 ternary complex formation. AB - Translation is a fundamental cellular process, and its dysregulation can contribute to human diseases such as cancer. During translation initiation the eukaryotic initiation factor 2 (eIF2) forms a ternary complex (TC) with GTP and the initiator methionyl-tRNA (tRNAi), mediating ribosomal recruitment of tRNAi. Limiting TC availability is a central mechanism for triggering the integrated stress response (ISR), which suppresses global translation in response to various cellular stresses, but induces specific proteins such as ATF4. This study shows that OLA1, a member of the ancient Obg family of GTPases, is an eIF2-regulatory protein that inhibits protein synthesis and promotes ISR by binding eIF2, hydrolyzing GTP, and interfering with TC formation. OLA1 thus represents a novel mechanism of translational control affecting de novo TC formation, different from the traditional model in which phosphorylation of eIF2alpha blocks the regeneration of TC. Depletion of OLA1 caused a hypoactive ISR and greater survival in stressed cells. In vivo, OLA1-knockdown rendered cancer cells deficient in ISR and the downstream proapoptotic effector, CHOP, promoting tumor growth and metastasis. Our work suggests that OLA1 is a novel translational GTPase and plays a suppressive role in translation and cell survival, as well as cancer growth and progression. PMID- 26283181 TI - Optimizing RNA structures by sequence extensions using RNAcop. AB - A key aspect of RNA secondary structure prediction is the identification of novel functional elements. This is a challenging task because these elements typically are embedded in longer transcripts where the borders between the element and flanking regions have to be defined. The flanking sequences impact the folding of the functional elements both at the level of computational analyses and when the element is extracted as a transcript for experimental analysis. Here, we analyze how different flanking region lengths impact folding into a constrained structure by computing probabilities of folding for different sizes of flanking regions. Our method, RNAcop (RNA context optimization by probability), is tested on known and de novo predicted structures. In vitro experiments support the computational analysis and suggest that for a number of structures, choosing proper lengths of flanking regions is critical. RNAcop is available as web server and stand-alone software via http://rth.dk/resources/rnacop. PMID- 26283182 TI - The role of wobble uridine modifications in +1 translational frameshifting in eukaryotes. AB - In Saccharomyces cerevisiae, 11 out of 42 tRNA species contain 5 methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U), 5-methoxycarbonylmethyluridine (mcm(5)U), 5-carbamoylmethyluridine (ncm(5)U) or 5-carbamoylmethyl-2'-O methyluridine (ncm(5)Um) nucleosides in the anticodon at the wobble position (U34). Earlier we showed that mutants unable to form the side chain at position 5 (ncm(5) or mcm(5)) or lacking sulphur at position 2 (s(2)) of U34 result in pleiotropic phenotypes, which are all suppressed by overexpression of hypomodified tRNAs. This observation suggests that the observed phenotypes are due to inefficient reading of cognate codons or an increased frameshifting. The latter may be caused by a ternary complex (aminoacyl-tRNA*eEF1A*GTP) with a modification deficient tRNA inefficiently being accepted to the ribosomal A-site and thereby allowing an increased peptidyl-tRNA slippage and thus a frameshift error. In this study, we have investigated the role of wobble uridine modifications in reading frame maintenance, using either the Renilla/Firefly luciferase bicistronic reporter system or a modified Ty1 frameshifting site in a HIS4A::lacZ reporter system. We here show that the presence of mcm(5) and s(2) side groups at wobble uridines are important for reading frame maintenance and thus the aforementioned mutant phenotypes might partly be due to frameshift errors. PMID- 26283184 TI - Use of a collagen matrix for recession coverage in patients who received orthodontic therapy: a case series. AB - AIM: The aim of the present study was to determine the percentage of recession coverage achieved following surgery with a collagen matrix, and patient-reported outcome measures. METHODS: Five healthy adults who had completed orthodontic therapy with a gingival recession defect were recruited. Gingival recession coverage was performed using a two-layer, xenogeneic collagen matrix (Mucograft). During the first 2 weeks, the patients charted their perceptions on bleeding, swelling, pain, and bruising using a visual analog scale (VAS). Post-surgical complications were assessed clinically at 1 week, 2 weeks, and 1 month post surgery. Recession dimensions were examined at 1, 3, 6, and 12 months. RESULTS: At 1 year, an average of 67% root coverage was achieved. The amount of recession coverage achieved was stable from 3 months. The results were maintained at 1 year. There were no post-surgical complications. All VAS parameters decreased to almost zero by day 14. From day 1, bleeding and pain decreased over time. However, there were peaks on days 2 and 3 for swelling and bruising, respectively, followed by a subsequent decrease. CONCLUSIONS: The use of Mucograft for recession coverage is effective and safe, with low morbidity and no post-surgical complications. Recession coverage achieved at 3 months remained stable in the 1-year follow-up period. PMID- 26283183 TI - Local sequence assembly reveals a high-resolution profile of somatic structural variations in 97 cancer genomes. AB - Genomic structural variations (SVs) are pervasive in many types of cancers. Characterizing their underlying mechanisms and potential molecular consequences is crucial for understanding the basic biology of tumorigenesis. Here, we engineered a local assembly-based algorithm (laSV) that detects SVs with high accuracy from paired-end high-throughput genomic sequencing data and pinpoints their breakpoints at single base-pair resolution. By applying laSV to 97 tumor normal paired genomic sequencing datasets across six cancer types produced by The Cancer Genome Atlas Research Network, we discovered that non-allelic homologous recombination is the primary mechanism for generating somatic SVs in acute myeloid leukemia. This finding contrasts with results for the other five types of solid tumors, in which non-homologous end joining and microhomology end joining are the predominant mechanisms. We also found that the genes recursively mutated by single nucleotide alterations differed from the genes recursively mutated by SVs, suggesting that these two types of genetic alterations play different roles during cancer progression. We further characterized how the gene structures of the oncogene JAK1 and the tumor suppressors KDM6A and RB1 are affected by somatic SVs and discussed the potential functional implications of intergenic SVs. PMID- 26283185 TI - Management of Acute Respiratory Failure in Patients With Hematological Malignancy. AB - Acute respiratory failure (ARF) is the leading cause of intensive care unit admission in patients with hematologic malignancies and is associated with a high mortality. The main causes of ARF are bacterial and opportunistic pulmonary infections and noninfectious lung disorders. Management consists of a systematic clinical evaluation aimed at identifying the most likely cause, which in turn determines the best first-line empirical treatments. The need for mechanical ventilation is a major determinant of prognosis. Beneficial outcomes have been demonstrated with early use of noninvasive ventilation (NIV) in selected patients with hematologic malignancies. However, most of these studies did not control the time between onset of ARF to NIV implementation nor accounted for the etiology of ARF or the presence of associated organ dysfunction at the time of NIV initiation. Moreover, the benefits demonstrated with NIV in these patients were derived from studies with high mortality rates of intubated patients. Additional studies are therefore warranted to determine the appropriate patients with hematologic malignancy and ARF who may benefit from prophylactic or curative NIV. PMID- 26283186 TI - Integrating immune mechanisms to model nematode worm burden: an example in sheep. AB - Gastrointestinal nematodes represent important sources of economic losses in farmed ruminants, and the increasing frequency of anthelmintic resistance requires an increased ability to explore alternative strategies. Theoretical approaches at the crossroads of immunology and epidemiology are valuable tools in that context. In the case of Teladorsagia circumcincta in sheep, the immunological mechanisms important for resistance are increasingly well characterized. However, despite the existence of a wide range of theoretical models, there is no framework integrating the characteristic features of this immune response into a tractable phenomenological model. Here, we propose to bridge that gap by developing a flexible modelling framework that allows for variability in nematode larval intake which can be used to track the variations in worm burdens. We parameterize this model using data from trickle infection of sheep and show that using simple immunological assumptions, our model can capture the dynamics of both adult worm burdens and nematode fecal egg counts. In addition, our analysis reveals interesting dose-dependent effects on the immune response. Finally, we discuss potential developments of this model and highlight how an improved cross-talk between empiricists and theoreticians would facilitate important advances in the study of infectious diseases. PMID- 26283188 TI - Distributed curvature and stability of fullerenes. AB - Energies of non-planar conjugated pi systems are typically described qualitatively in terms of the balance of pi stabilisation and the steric strain associated with geometric curvature. Curvature also has a purely graph theoretical description: combinatorial curvature at a vertex of a polyhedral graph is defined as one minus half the vertex degree plus the sum of reciprocal sizes of the faces meeting at that vertex. Prisms and antiprisms have positive combinatorial vertex curvature at every vertex. Excluding these two infinite families, we call any other polyhedron with everywhere positive combinatorial curvature a PCC polyhedron. Cubic PCC polyhedra are initially common, but must eventually die out with increasing vertex count; the largest example constructed so far has 132 vertices. The fullerenes Cn have cubic polyhedral molecular graphs with n vertices, 12 pentagonal and (n/2 - 10) hexagonal faces. We show that there are exactly 39 PCC fullerenes, all in the range 20 <=n<= 60. In this range, there is only partial correlation between PCC status and stability as defined by minimum pentagon adjacency. The sum of vertex curvatures is 2 for any polyhedron; for fullerenes the sum of squared vertex curvatures is linearly related to the number of pentagon adjacencies and hence is a direct measure of relative stability of the lower (n<= 60) fullerenes. For n>= 62, non-PCC fullerenes with a minimum number of pentagon adjacencies minimise mean-square curvature. For n>= 70, minimum mean-square curvature implies isolation of pentagons, which is the strongest indicator of stability for a bare fullerene. PMID- 26283187 TI - Psychosocial Adaptation to Disability Within the Context of Positive Psychology: Findings from the Literature. AB - PURPOSE: This purpose of this article is to review of the trends of research that examined positive psychology constructs in the context of adapting to chronic illness and disability (CID). This article examines the empirical findings on the relationships between six selected positive psychology-associated constructs (optimism, hope, resilience, benefit-finding, meaning-making, and post-traumatic growth) and adaptation to disability. METHODS: Six positive psychology constructs were selected to represent the trends found in recent literature published on CID. The process of choosing these six variables included reviewing chapters on positive psychology and CID, reviewing the top rehabilitation journals that typically publish articles on psychosocial adaptation to CID, using search engines to find relevant journal articles published since the year 2000, and selecting the most important constructs based on the authors' professional judgment. CONCLUSION: The available evidence supports the unique benefits of these six positive psychology constructs in predicting successful adaptation to a range of disabling conditions. Based on the available findings, the authors offer four suggestions for occupational rehabilitation researchers. PMID- 26283191 TI - Determination of Flower Constancy in Bombus atratus Franklin and Bombus bellicosus Smith (Hymenoptera: Apidae) through Palynological Analysis of Nectar and Corbicular Pollen Loads. AB - The flower constancy (the visit to a single plant species during a foraging trip) in pollinator insects is a theme widely discussed in behavioral ecology and has an important implication in the evolution of angiosperms. This behavior was studied in the bumblebees Bombus atratus Franklin and Bombus bellicosus Smith through palynological analysis of the nectar and pollen loads of individuals captured while foraging in a restricted area. In both species, there were more individuals with constant flights than with non-constant ones, although in the nectar loads of B. atratus there were no significant differences between individuals with each flight types. It was verified that the nectar loads of the individuals that made either constant or non-constant flights did not differ in the number of pollen grains they contained. Considering this measurement as an estimate for flight duration, the results would indicate that the probability of changing between plant species during nectar collection is independent of the foraging trip duration. In both species, most individuals who collected nectar and/or pollen from more than one plant species visited just two plant species. In these cases, the pollen of one plant species was predominant. In the bumblebees in which it was possible to analyze nectar and pollen loads, the botanical origin of both resources was the same or they shared the principal species (with the exception of two individuals), showing that bumblebees do not often use a botanical source in an exclusive way to collect nectar and another to collect pollen. PMID- 26283189 TI - Relating off-premises alcohol outlet density to intentional and unintentional injuries. AB - AIMS: This study investigated the hypotheses that (i) intentional and unintentional injuries occur more frequently in areas with greater density of off premises alcohol outlets; and (ii) larger and chain outlets selling cheaper alcohol contribute more substantially to injury risk than smaller and independent outlets. DESIGN: Ecological cross-sectional. SETTING: From the 256 Statistical Area level 2 (SA2) census units in Melbourne, Australia, we selected a random sample of 62 units. There were 2119 Statistical Area level 1 (SA1) units nested within the selected SA2 units. PARTICIPANTS: The selected units contained 295 off premises outlets. MEASUREMENTS: Two independent observers conducted premises assessments in all off-premises outlets, assessing the volume of alcohol available for sale (paces of shelf space), price (least wine price) and other operating characteristics (chain versus independent, drive-through). Outlet counts, assessed outlet characteristics and other area characteristics (population density, median age, median income, retail zoning) were aggregated within SA1 units. Dependent variables were counts of ambulance attended intentional injuries (assaults, stabbings, shootings) and unintentional injuries (falls, crush injuries and object strikes). FINDINGS: In univariable analyses, chain outlets were larger (r = 0.383; P < 0.001) and sold cheaper alcohol (r = 0.484; P < 0.001) compared with independent outlets. In Bayesian spatial Poisson models, off-premises outlet density was positively related to both intentional [incidence rate ratio (IRR) = 1.38; 95% credible interval (CI) = 1.19, 1.60] and unintentional injuries (IRR = 1.18; 95% CI = 1.06, 1.30). After disaggregation by outlet characteristics, chain outlet density was also related to both intentional (IRR = 1.35; 95% CI = 1.11, 1.64) and unintentional injuries (IRR = 1.20; 95% CI = 1.08, 1.38). CONCLUSIONS: Greater off-premises outlet density is related to greater incidence of traumatic injury, and chain outlets appear to contribute most substantially to traumatic injury risk. PMID- 26283192 TI - Association of osteolytic lesions, bone mineral loss and trabecular sclerosis with prevalent vertebral fractures in patients with multiple myeloma. AB - PURPOSE: In patients with multiple myeloma (MM), computed tomography is widely used for staging and to detect fractures. Detecting patients at severe fracture risk is of utmost importance. However the criteria for impaired stability of vertebral bodies are not yet clearly defined. We investigated the performance of parameters that can be detected by the radiologist for discrimination of patients with and without fractures. METHODS AND MATERIALS: We analyzed 128 whole body low dose CT of MM patients. In all scans a QCT calibration phantom was integrated into the positioning mat (Image Analysis Phantom((r))). A QCT-software (Structural Insight) performed the volumetric bone mineral density (vBMD) measurements. Description of fracture risk was provided from the clinical radiological report. Suspected progressive disease (PD) was reported by the referring clinicians. Two radiologists that were blinded to study outcome reported on the following parameters based on predefined criteria: reduced radiodensity in the massa lateralis of the os sacrum (RDS), trabecular thickening and sclerosis of three or more vertebrae (TTS), extraosseous MM manifestations (EOM), visible small osteolytic lesions up to a length of 8mm (SO) and osteolytic lesions larger than 8mm (LO). Prevalent vertebral fractures (PVF) were defined by Genant criteria. Age-adjusted standardized odds ratios (sOR) per standard deviation change were derived from logistic regression analysis and area under the curve (AUC) from receiver operating characteristics (ROC) analyses were calculated. ROC curves were compared using the DeLong method. RESULTS: 45% of the 128 patients showed PVF (29 of 75 men, 24 of 53 women). Patients with PVF were not significantly older than patients without fractures (64.6 +/- 9.2 vs. 63.3 +/ 12.3 years: mean +/- SD, p=0.5). The prevalence of each parameter did not differ significantly by sex. Significant fracture discrimination for age adjusted single models was provided by the parameters vBMD (OR 3.5 [1.4-8.8], AUC=0.64 +/- 0.14), SO (sOR 1.6[1.1-2.2], AUC=0.63 +/- 0.05), LO (sOR 2.1[1.1-4.2] AUC=0.69 +/- 0.05) and RDS (sOR 2.6[1.6-4.7], AUC=0.69 +/- 0.05). Multivariate models of these four parameters showed a significantly stronger association with the development of PVF (AUC=0.80 +/- 0.04) than single variables. TTS showed a significant association with PVF in men(sOR 1.5 [0.8-3.0], AUC=0.63 +/- 0.08), but not in women (sOR 2.3[1.4-3.7], AUC=0.70 +/- 0.07). PD was significantly associated with PVF in women (sOR 1.9[1.1-3.6], AUC=0.67 +/- 0.08) but not in men (sOR 1.4[0.9 2.3], AUC=0.57 +/- .07). EOM were not associated with PVF (sOR 1.0[0.4-2.6], AUC=0.51 +/- .05). CONCLUSION: In multiple myeloma, focal skeletal changes in low dose CT scans show a significant association with prevalent vertebral fractures. The combination of large osteolytic lesions and loss in radiodensity as can be detected with simple CT Hounsfield measurements of the os sacrum or BMD measurements showed the strongest association to fractures and may be of value for prospective studies. PMID- 26283193 TI - Endometriosis: Does the menstrual cycle affect magnetic resonance (MR) imaging evaluation? AB - PURPOSE: To determine if the menstrual cycle affects MR interpretation in patients with pelvic endometriosis. MATERIALS AND METHODS: Thirty-one patients with either laparoscopically proven endometriosis, or a high clinical suspicion of deep infiltrative endometriosis, were prospectively recruited from May 2008 to October 2009 and January to June 2012. Two pelvic MR scans were performed for pre operative planning; during menses and the other mid-cycle. Two experienced radiologists independently assessed image quality and disease extent. Both were blinded to patient identity, previous imaging and menstrual status. Interobserver agreement was assessed using the Kappa (k) test. Descriptive statistics were prepared using chi-squared (or Fishers' exact) tests and Mann-Whitney (rank sum) tests to assess for significant differences between menstrual and non-menstrual imaging. RESULTS: Interobserver agreement for image quality was moderate for T2 weighted imaging (k=0.475, p-value <0.001) and substantial for T1 fat saturated imaging (k=0.733, p-value<0.001), with no significant difference in image quality between menstrual and non-menstrual scans (all p-values>0.255). Readers demonstrated at least moderate interobserver agreement for certainty level of endometriosis at site-specific locations, with median k 0.599 (IQR 0.488-0.807). No significant difference in disease extent was observed between menstruating and non-menstruating scans (all p-values>0.05). CONCLUSION: Findings suggest no significant differences in image quality, disease extent or disease severity between menstruating and non-menstruating MR; thus, timing of pelvic MR for assessment of endometriosis need not be influenced by the menstrual cycle. PMID- 26283194 TI - Assessment of urinary kidney injury molecule-1 and interleukin-18 in the early post-burn period to predict acute kidney injury for various degrees of burn injury. AB - BACKGROUND: Burn patients with AKI have a higher mortality, rapid diagnosis and early treatment of AKI are necessary. Recent studies have demonstrated that urinary KIM-1 and IL-18 are potential biomarkers of early-stage AKI, however, changes in urinary KIM-1 and IL-18 levels are unclear in patients with burns. The aim of our study was to determine whether combined KIM-1 and IL-18 are more sensitive than traditional markers in detecting kidney injury in patients with burns. METHODS: Ninety-five burn patients hospitalized at the Burns and Plastic Surgery Center of our hospital from April 2013 to September 2013 were enrolled into this prospective study and divided into mild- (n = 37), moderate- (n = 30) and severe-burn groups (n = 28) by burn injury surface area. In the moderate- and severe-burn groups, patients were subcategorized to either the acute kidney injury (AKI) group, in which serum creatinine (Scr) increased to >= 26.5 MUmol/L within 48 h, or the non-AKI group. Fifteen healthy subjects were selected as a control group. Blood specimens were collected to determine blood urea nitrogen (BUN), Scr, and other biochemical indicators. Urine samples collected at admission and 48 h after admission were analyzed for KIM-1 and IL-18. Correlations among urinary KIM-1 and IL-18, burn degree, and clinical biochemical indicators were investigated. RESULTS: AKI occurred in 11.2 % of burn patients (none in the mild-burn group). AKI developed 48 h after admission in 10.0 % of the moderate- and 28.6 % of the severe-burn groups. Urinary KIM-1 concentration in the moderate- and severe-burn groups was significantly higher than that in the control group; urinary IL-18 concentrations did not differ significantly among the burn and control groups. The AKI group had significantly higher concentrations of urinary KIM-1 and IL-18 than the non-AKI group, both at admission (p = 0.001 and p < 0.001, respectively) and 48 h later (p = 0.001 and p < 0.001, respectively). Both urinary KIM-1 and IL-18 increased before Scr. Receiver operating-curve (ROC) analysis demonstrated that KIM-1 combined with IL 18 predicted AKI with 72.7 % sensitivity and 92.8 % specificity. The area under the ROC curve was 0.904. CONCLUSIONS: Our results suggest that urinary KIM-1 and IL-18 may be used as early, sensitive indicators of AKI in patients with burns of varying degrees and provide clinical clues that can be used in early prevention of AKI. PMID- 26283195 TI - Preparation and Evaluation of Diclofenac Sodium Tablet Coated with Polyelectrolyte Multilayer Film Using Hypromellose Acetate Succinate and Polymethacrylates for pH-Dependent, Modified Release Drug Delivery. AB - Polyelectrolyte multilayer (PEM) film formed due to the electrostatic interaction between oppositely charged polyelectrolytes is of considerable interest because of their potential applications as both drug carriers and surface-modifying agents. In this study, in vitro studies were carried out on polyelectrolyte complexes formulated with Eudragit E (EE) and hypromellose acetate succinate (HPMCAS). The complexes of EE and HPMCAS were formulated by non-stoichiometric method. The prepared IPCs were investigated using Fourier transform infrared spectroscopy. Diclofenac sodium (DS) tablets were prepared and were coated with polymer solution of HPMCAS and EE to achieve pH-dependent and sustained-release tablets. Tablets were evaluated for their physical characteristics and in vitro drug release. The results of pharmacokinetic studies in rabbits showed that the selected formulation (F6) exhibited a delayed peak plasma concentration and marked sustained-release effect of drug in the in vivo drug release in comparison with marketed tablet. The suitable combination of PEM film based on EE and HPMCAS demonstrated potential candidate for targeted release of DS in the lower part of the gastrointestinal (GI) tract. PMID- 26283196 TI - Assessing Mixing Quality of a Copovidone-TPGS Hot Melt Extrusion Process with Atomic Force Microscopy and Differential Scanning Calorimetry. AB - Atomic force microscopy (AFM) and modulated differential scanning calorimetry (mDSC) were used to evaluate the extent of mixing of a hot melt extrusion process for producing solid dispersions of copovidone and D-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS 1000). In addition to composition, extrusion process parameters of screw speed and thermal quench rate were varied. The data indicated that for 10% TPGS and 300 rpm screw speed, the mixing was insufficient to yield a single-phase amorphous material. AFM images of the extrudate cross section for air-cooled material indicate round domains 200 to 700 nm in diameter without any observed alignment resulting from the extrusion whereas domains in extrudate subjected to chilled rolls were elliptical in shape with uniform orientation. Thermal analysis indicated that the domains were predominantly semi-crystalline TPGS. For 10% TPGS and 600 rpm screw speed, AFM and mDSC data were consistent with that of a single-phase amorphous material for both thermal quench rates examined. When the TPGS concentration was reduced to 5%, a single-phase amorphous material was achieved for all conditions even the slowest screw speed studied (150 rpm). PMID- 26283197 TI - Conjugation of Hot-Melt Extrusion with High-Pressure Homogenization: a Novel Method of Continuously Preparing Nanocrystal Solid Dispersions. AB - Over the past few decades, nanocrystal formulations have evolved as promising drug delivery systems owing to their ability to enhance the bioavailability and maintain the stability of poorly water-soluble drugs. However, conventional methods of preparing nanocrystal formulations, such as spray drying and freeze drying, have some drawbacks including high cost, time and energy inefficiency, traces of residual solvent, and difficulties in continuous operation. Therefore, new techniques for the production of nanocrystal formulations are necessary. The main objective of this study was to introduce a new technique for the production of nanocrystal solid dispersions (NCSDs) by combining high-pressure homogenization (HPH) and hot-melt extrusion (HME). Efavirenz (EFZ), a Biopharmaceutics Classification System class II drug, which is used for the treatment of human immunodeficiency virus (HIV) type I, was selected as the model drug for this study. A nanosuspension (NS) was first prepared by HPH using sodium lauryl sulfate (SLS) and Kollidon(r) 30 as a stabilizer system. The NS was then mixed with Soluplus(r) in the extruder barrel, and the water was removed by evaporation. The decreased particle size and crystalline state of EFZ were confirmed by scanning electron microscopy, zeta particle size analysis, and differential scanning calorimetry. The increased dissolution rate was also determined. EFZ NCSD was found to be highly stable after storage for 6 months. In summary, the conjugation of HPH with HME technology was demonstrated to be a promising novel method for the production of NCSDs. PMID- 26283198 TI - Lidocaine Transdermal Patch: Pharmacokinetic Modeling and In Vitro-In Vivo Correlation (IVIVC). AB - The present study aims to develop the correlation between in vitro and in vivo skin permeation of lidocaine in its transdermal patch. In order to minimize the run-to-run variability during in vitro skin permeation studies, release normalized cumulative percent (%Ct n) was calculated. A suitable polynomial mathematical model was used to establish a correlation between time and %Ct n. Percent in vivo absorbed was calculated by using numerical deconvolution (NDC) and non-compartmental analysis (NCA) methods. Pharmacokinetic (PK) parameters such as AUC last and C max were predicted with the established in vitro-in vivo correlation (IVIVC) models. The minimum prediction errors in NDC method for C max were found to be -30.9 and -25.4% for studies I (in vivo study in human volunteers with one batch of Lidoderm patch; internal validation) and II (in vivo study in human volunteers with another batch of Lidoderm patch; external validation), respectively, whereas minimum prediction errors in NCA method were relatively low (3.9 and 0.03% for studies I and II, respectively) compared to those in NDC method. The prediction errors for AUC last were found to be less than 2% for both methods and studies. The established method in this study could be a potential approach for predicting the bioavailability and/or bioequivalence for transdermal drug delivery systems. PMID- 26283199 TI - Constitutive and ghrelin-dependent GHSR1a activation impairs CaV2.1 and CaV2.2 currents in hypothalamic neurons. AB - The growth hormone secretagogue receptor type 1a (GHSR1a) has the highest known constitutive activity of any G protein-coupled receptor (GPCR). GHSR1a mediates the action of the hormone ghrelin, and its activation increases transcriptional and electrical activity in hypothalamic neurons. Although GHSR1a is present at GABAergic presynaptic terminals, its effect on neurotransmitter release remains unclear. The activities of the voltage-gated calcium channels, CaV2.1 and CaV2.2, which mediate neurotransmitter release at presynaptic terminals, are modulated by many GPCRs. Here, we show that both constitutive and agonist-dependent GHSR1a activity elicit a strong impairment of CaV2.1 and CaV2.2 currents in rat and mouse hypothalamic neurons and in a heterologous expression system. Constitutive GHSR1a activity reduces CaV2 currents by a Gi/o-dependent mechanism that involves persistent reduction in channel density at the plasma membrane, whereas ghrelin dependent GHSR1a inhibition is reversible and involves altered CaV2 gating via a Gq-dependent pathway. Thus, GHSR1a differentially inhibits CaV2 channels by Gi/o or Gq protein pathways depending on its mode of activation. Moreover, we present evidence suggesting that GHSR1a-mediated inhibition of CaV2 attenuates GABA release in hypothalamic neurons, a mechanism that could contribute to neuronal activation through the disinhibition of postsynaptic neurons. PMID- 26283200 TI - Structural implications of weak Ca2+ block in Drosophila cyclic nucleotide-gated channels. AB - Calcium permeability and the concomitant calcium block of monovalent ion current ("Ca(2+) block") are properties of cyclic nucleotide-gated (CNG) channel fundamental to visual and olfactory signal transduction. Although most CNG channels bear a conserved glutamate residue crucial for Ca(2+) block, the degree of block displayed by different CNG channels varies greatly. For instance, the Drosophila melanogaster CNG channel shows only weak Ca(2+) block despite the presence of this glutamate. We previously constructed a series of chimeric channels in which we replaced the selectivity filter of the bacterial nonselective cation channel NaK with a set of CNG channel filter sequences and determined that the resulting NaK2CNG chimeras displayed the ion selectivity and Ca(2+) block properties of the parent CNG channels. Here, we used the same strategy to determine the structural basis of the weak Ca(2+) block observed in the Drosophila CNG channel. The selectivity filter of the Drosophila CNG channel is similar to that of most other CNG channels except that it has a threonine at residue 318 instead of a proline. We constructed a NaK chimera, which we called NaK2CNG-Dm, which contained the Drosophila selectivity filter sequence. The high resolution structure of NaK2CNG-Dm revealed a filter structure different from those of NaK and all other previously investigated NaK2CNG chimeric channels. Consistent with this structural difference, functional studies of the NaK2CNG-Dm chimeric channel demonstrated a loss of Ca(2+) block compared with other NaK2CNG chimeras. Moreover, mutating the corresponding threonine (T318) to proline in Drosophila CNG channels increased Ca(2+) block by 16 times. These results imply that a simple replacement of a threonine for a proline in Drosophila CNG channels has likely given rise to a distinct selectivity filter conformation that results in weak Ca(2+) block. PMID- 26283201 TI - All roads lead to presynaptic calcium channel inhibition by the ghrelin receptor: Separate agonist-dependent and -independent signaling pathways. PMID- 26283204 TI - Outcomes of a proficiency-based skills curriculum at the beginning of the fourth year for senior medical students entering surgery. AB - INTRODUCTION: We hypothesized that a proficiency-based curriculum administered early in the fourth year to senior medical students (MS4) would achieve outcomes comparable to a similar program administered during surgical internship. METHODS: MS4 (n = 18) entering any surgical specialty enrolled in a proficiency-based skills curriculum at the beginning of the fourth year that included suturing/knot tying, on-call problems, laparoscopic, and other skills (urinary catheter, sterile prep/drape, IV placement, informed consent, electrosurgical use). Assessment was at 4-12 weeks after training by a modified Objective Structured Assessment of Technical Skills (OSATS). Suturing and knot tying tasks were assessed by time and OSATS technical proficiency (TP) scores (1 [novice], 3 [proficient], 5 [expert]). Outcomes were compared with PGY-1 residents who received similar training at the beginning of internship and assessment 4-12 weeks later. Data are presented as mean values +/- standard deviation; statistical significance was assessed by Student's t test. RESULTS: Fifteen of 18 MS4 (83%) reached proficiency on all 15 tasks, and 2 others were proficient on all but 1 laparoscopic task. Compared with PGY-1s, MS4 were significantly faster for 3 of 5 suturing and tying tasks and total task time (547 +/- 63 vs 637 +/- 127 s; P < .05). Mean TP scores were similar for both groups (MS4, 3.4 +/- 0.5 vs PGY-1, 3.1 +/- .57; P = NS). MS4 OSATS scores were higher for IV placement, informed consent, and urinary catheter placement, but lower for prep and drape and for management of on-call problems. CONCLUSION: MS4 who participate in a proficiency-based curriculum taught early in the fourth year are able to meet proficiency targets in a high percentage of cases. This approach should better prepare MS4 for surgical internship. PMID- 26283205 TI - Fine-needle aspiration cytology in the evaluation of patients with radiographically occult, palpable breast abnormalities. AB - BACKGROUND: Patients who present with occult, palpable breast abnormalities on radiographs represent a diagnostic challenge. We hypothesized that fine-needle aspiration cytology (FNAC) would be an accurate method for diagnosing and excluding malignancy in these patients. METHODS: The records of all patients undergoing FNAC at our institution between 2010 and 2012 were queried; 173 patients with 175 palpable breast masses without an imaging correlate were included. RESULTS: Of 175 FNAC performed, 2 (1%) were malignant, 16 (9%) were suspicious, and 157 (90%) were benign (n = 75) or nondiagnostic (n = 82). All 16 suspicious FNAC underwent an additional biopsy, of which 4 were malignant. FNAC led to the identification of 6 (3.4%) occult malignancies. At a median follow-up of 16.3 months, 1 patient within the benign cohort was found to have an incidental 2.5 mm cancer identified on reduction mammaplasty, which was unrelated to the index mass. The negative predictive value of FNAC in benign patients was 100%. CONCLUSION: FNAC detected malignancy in a small but significant percentage of patients with a palpable mass and negative breast imaging while excluding carcinoma in the remaining patients. FNAC may be included in the evaluation of patients with occult, palpable breast masses demonstrated on radiography. PMID- 26283208 TI - Trauma centers with higher rates of angiography have a lesser incidence of splenectomy in the management of blunt splenic injury. AB - BACKGROUND: Nonoperative management (NOM) for blunt splenic injury (BSI) is well established. Angiography (ANGIO) has been shown to improve success rates with NOM. Protocols for NOM are not standardized and vary widely between centers. We hypothesized that trauma centers that performed ANGIO at a greater rate would demonstrate decreased rates of splenectomy compared with trauma centers that used ANGIO less frequently. METHODS: A large, multicenter, statewide database (Pennsylvania Trauma Systems Foundation) from 2007 to 2011 was used to generate the study cohort of patients with BSI (age >= 13). The cohort was divided into 2 populations based on admission to centers with high (>=13%) or low (<13%) rates of ANGIO. Patient demographics, grade of BSI, Injury Severity Score, level of trauma center designation, and patient volume were analyzed. Splenectomy rates were then compared between the 2 groups, and multivariable logistic regression for predictors of splenectomy (failed NOM) were also performed. RESULTS: The overall rate of splenectomy in the entire cohort was 21.0% (1,120 of 5,333 BSI patients). The high ANGIO group had a lesser rate of splenectoy compared with the low ANGIO group (19% vs 24%; P < .001). Treatment at high ANGIO centers was negatively associated with splenectomy compared with low ANGIO centers (odds ratio, 0.68; 95% CI 0.58-0.80; P < .001); this association was independent of the number of BSI admissions or level of trauma center designation. CONCLUSION: Treatment of BSI at trauma centers that performed ANGIO more frequently resulted in lesser splenectomy rates compared with centers with lesser rate of ANGIO. Inclusion of angiographic protocols for NOM of BSI should be considered strongly. PMID- 26283207 TI - Resveratrol decreases nitric oxide production by hepatocytes during inflammation. AB - INTRODUCTION: The production of excessive amounts of nitric oxide (NO) through inducible nitric oxide synthase (iNOS) contributes to organ injury, inflammation, and mortality after shock. Resveratrol (RSV) is a natural polyphenol that decreases shock-induced hepatic injury and inflammation. We hypothesized that RSV would mediate these effects by decreasing hepatocyte iNOS production. METHODS: Rat hepatocytes were isolated, cultured with varying concentrations of RSV, and then stimulated to induce iNOS with interleukin-1 and interferon. Induction of iNOS protein was measured by Western blot, iNOS mRNA by polymerase chain reaction, and NO production was measured by culture supernatant nitrite. Activation of intracellular signaling pathways involving Akt, c-Jun N-terminal kinase (JNK), and nuclear factor kappaB (NF-kappaB) were measured by Western blot using isoform-specific antibodies. RESULTS: RSV decreased the expression of iNOS mRNA, protein, and supernatant nitrite in a dose-dependent manner. Our previous work demonstrated that Akt and JNK both inhibit hepatic iNOS production, whereas NF-kappaB increases iNOS expression. Analysis of signaling pathways in this study demonstrated that RSV increased JNK phosphorylation but decreased Akt phosphorylation and increased NF-kappaB activation. CONCLUSION: RSV decreases cytokine-induced hepatocyte iNOS expression, possibly through up-regulation of the JNK signaling pathway. RSV merits further investigation to determine its mechanism as a compound that can decrease inflammation after shock. PMID- 26283210 TI - CARD8 gene variant is a risk factor for recurrent surgery in patients with Crohn's disease. AB - BACKGROUND AND AIMS: Post-operative recurrence is frequent in Crohn's disease. Genetic factors associated with post-operative recurrence remain poorly understood. Identification of genetic variants associated with repeat surgery would allow risk stratification of patients who may benefit from early aggressive therapy and/or post-operative prophylactic treatment. METHODS: Crohn's disease patients who had at least one bowel resection were retrospectively identified from the "Nancy IBD cohort". Covariates and potential interactions were assessed using the Cox proportional hazard model. Kaplan-Meier curves for time to surgical recurrence were developed for 200 genetic variants and analyzed with the log-rank test. RESULTS: 137 patients had at least 1 resection in our cohort: 38 had a surgical recurrence (28%). In multivariate analysis, current smoker status (OR 6.97, 95% CI 1.85-26.22, p=0.004), post-operative complications after prior surgery (OR 2.72, 95% CI 1.02-7.22, p=0.044), and Caspase recruitment domain containing protein 8 (CARD8) homozygosity for the risk allele (OR 7.56, 95% CI 1.13-50.37, p=0.036) remained significantly and independently associated with surgical recurrence. CONCLUSION: Current smoker status was associated with increased risk of surgical recurrence. A novel association between CARD8 and increased risk of surgical recurrence in Crohn's disease was observed. CARD8 could be a new marker for risk stratification and prevention of recurrent surgery. PMID- 26283211 TI - Quality of life in children with celiac disease: A paediatric cross-sectional study. AB - BACKGROUND: Few studies investigated factors influencing the quality of life of children with celiac disease on a gluten-free diet. AIMS: To investigate the impact of the gluten-free diet on the psycho-physical well-being of celiac children. METHODS: In this cross-sectional study, we interviewed 76 celiac and 143 non-celiac children (2-18 years) by using a non-disease specific questionnaire (Pediatric Quality of Life Inventory Test) and we explored the impact of the diet on social life with an open-ended questionnaire. Scores were compared by Wilcoxon rank-sum test. A quantile regression analysis was used to evaluate the impact of celiac disease on score distribution. RESULTS: No significant differences in quality of life were found between the two groups (total score: 84.1 (81.1-87.2) vs 81.5 (79.7-83.4), median (95% CI), patients and controls respectively, p=0.4). Treatment positively affected quality of life in children that showed "intermediate" scores in the Pediatric Quality of Life Inventory Test. Lowest scores were observed in children reporting a higher number of diet difficulties or co-morbidities. CONCLUSIONS: Although celiac patients showed an overall good quality of life in comparison with a control group, by using appropriate analytical methods we elicited specific factors contributing to a lower quality of life in patients, such as co-morbidities and difficulties with the diet. PMID- 26283212 TI - Cannabidiol, a Cannabis sativa constituent, inhibits cocaine-induced seizures in mice: Possible role of the mTOR pathway and reduction in glutamate release. AB - Cannabidiol (CBD), a major non-psychotomimetic constituent of Cannabis sativa, has therapeutic potential for certain psychiatric and neurological disorders. Studies in laboratory animals and limited human trials indicate that CBD has anticonvulsant and neuroprotective properties. Its effects against cocaine neurotoxicity, however, have remained unclear. Thus, the present study tested the hypothesis that CBD protects against cocaine-induced seizures and investigated the underlying mechanisms. CBD (30 mg/kg) pre-treatment increased the latency and reduced the duration of cocaine (75 mg/kg)-induced seizures in mice. The CB1 receptor antagonist, AM251 (1 and 3mg/kg), and the CB2 receptor antagonist, AM630 (2 and 4 mg/kg), failed to reverse this protective effect, suggesting that alternative mechanisms are involved. Synaptosome studies with the hippocampus of drug-treated animals revealed that cocaine increases glutamate release, whereas CBD induces the opposite effect. Finally, the protective effect of this cannabinoid against cocaine-induced seizure was reversed by rapamycin (1 and 5mg/kg), an inhibitor of the mammalian target of rapamycin (mTOR) intracellular pathway. In conclusion, CBD protects against seizures in a model of cocaine intoxication. These effects possibly occur through activation of mTOR with subsequent reduction in glutamate release. CBD should be further investigated as a strategy for alleviating psychostimulant toxicity. PMID- 26283214 TI - Melatonin attenuates methamphetamine-induced neuroinflammation through the melatonin receptor in the SH-SY5Y cell line. AB - Methamphetamine is a well-known psychostimulant drug, the abuse of which is a serious worldwide public health issue. In addition to its addictive effect, methamphetamine exposure has been shown to be associated with neuroinflammation in several brain areas. Several lines of evidence indicate that TNFalpha plays an important role in the methamphetamine-induced neuroinflammatory processes that result in apoptotic cell death. Many investigators have demonstrated the anti neuroinflammatory effects of melatonin, but the mechanism by which this occurs still needs to be explored. In this study, we investigated the effect of methamphetamine on TNFalpha expression and NFkappaB activation in the neuroblastoma cell line SH-SY5Y. We demonstrated the time-dependent effect of methamphetamine on the induction of TNFalpha expression as well as IkappaB degradation and NFkappaB nuclear translocation. Furthermore, we investigated the effect of melatonin on methamphetamine-induced TNFalpha overexpression and NFkappaB activation. The results showed that pretreatment with 100nM melatonin could prevent the TNFalpha overexpression caused by methamphetamine exposure. This attenuating effect was prevented by pre-incubation with luzindole, an antagonist of the melatonin MT1/MT2 receptors. Furthermore, methamphetamine induced IkappaB degradation and NFkappaB nuclear translocation were also suppressed by pretreatment with melatonin, and pretreatment with luzindole diminished these protective effects. MT2 knockdown by siRNA abrogated the anti inflammatory effect exerted by melatonin. From these findings, we propose that melatonin exerts its protective effects on methamphetamine-induced neuroinflammation through the membrane receptor, at least in part MT2 subtype, in the SH-SY5Y neuroblastoma cell line. PMID- 26283213 TI - Characterization of binge-dosed methamphetamine-induced neurotoxicity and neuroinflammation. AB - Methamphetamine (MA) is a potent, highly addictive psychostimulant abused by millions of people worldwide. MA induces neurotoxicity, damaging striatal dopaminergic terminals, and neuroinflammation, with striatal glial activation leading to pro-inflammatory cytokine and reactive oxygen species production. It is unclear whether MA-induced neuroinflammation contributes to MA-induced neurotoxicity. In the current study, we examined the linkage between the time course and dose response of MA-induced neurotoxicity and neuroinflammation. Adult male mice underwent a binge dosing regimen of four injections given every 2h with doses of 2, 4, 6, or 8 mg/kg MA per injection, and were sacrificed after 1, 3, 7, or 14 days. Binge MA treatment dose-dependently caused hyperthermia and induced hypoactivity after one day, though activity returned to control levels within one week. Striatal dopamine (DA) was diminished one day after treatment with at least 4 mg/kg MA, while DA turnover rates peaked after seven days. Although striatal tyrosine hydroxylase and DA transporter levels were also decreased one day after treatment with at least 4 mg/kg MA, they trended toward recovery by day 14. All doses of MA activated striatal glia within one day. While astrocyte activation persisted, microglial activation was attenuated over the two weeks of the study. These findings help clarify the relationship between MA-induced neuroinflammation and neurotoxicity, particularly regarding their temporal and dose-specific dynamics. PMID- 26283215 TI - A dual-FRET-based fluorescence probe for the sequential detection of MMP-2 and caspase-3. AB - A novel dual-FRET-based fluorescence probe was designed and synthesized for the sequential detection of MMP-2 and caspase-3. This probe can successfully monitor Dox- and UV-induced cell apoptosis signals in real time and in situ, which demonstrated its great potential for apoptosis-related drug screening and dynamic apoptosis imaging. PMID- 26283217 TI - Enteral glutamine supplementation in critically ill patients: a systematic review and meta-analysis. AB - INTRODUCTION: Glutamine (GLN) has been suggested to have a beneficial influence on outcomes of critically ill patients. However, recent large-scale trials have suggested harm associated with GLN supplementation. Recently, systematic reviews on the use of parenteral GLN have been published; however, less information is available on the role of enteral GLN. Therefore, the aim of this systematic review was to study the effects of enteral GLN supplementation in patients with critical illness. METHODS: We identified randomized controlled trials conducted from 1980 to 2014 with enterally administered GLN in adult critically ill patients. Studies of parenteral GLN only or combined enteral-parenteral GLN were excluded. The methodological quality of studies was scored, and trial data were statistically combined. We examined a priori the treatment effects in subgroups of trials of burn and trauma patients. RESULTS: A total of 11 studies involving 1079 adult critically ill patients and enteral GLN supplementation were identified. Enteral GLN supplementation was not associated with a reduction of hospital mortality (risk ratio [RR] 0.94, 95% confidence interval [CI] 0.65-1.36; p = 0.74), infectious complications (RR 0.93, 95% CI 0.79-1.10; p = 0.39) or stay in the intensive care unit (weighted mean difference [WMD] -1.36 days, 95% CI 5.51 to 2.78; p = 0.52). However, there was a significant reduction in hospital stay (WMD 4.73 days, 95% CI -8.53 to -0.90; p = 0.02). In the subset of studies of patients with burns, enteral GLN supplementation was associated with significant reductions in hospital mortality (RR 0.19, 95% 0.06-0.67; p = 0.010) and hospital stay (WMD -9.16, 95% CI -15.06 to -3.26; p = 0.002). There was no effect in trauma patients. CONCLUSIONS: Enteral GLN supplementation does not confer significant clinical benefit in critically ill patients, with the exception of reduced hospital stay. There may be a significant benefit in patients with burns, but data are sparse and larger randomized trials are warranted to confirm this effect. PMID- 26283219 TI - De Novo Heterogeneous Mutations in SCN2A and GRIN2A Genes and Seizures With Ictal Vocalizations. PMID- 26283220 TI - Persistent Vaginal Bleeding in a Six-Year-Old. PMID- 26283218 TI - Macular Star and Central Visual Loss: Two Pediatric Cases. PMID- 26283221 TI - Logging The BMJ's "patient journey". PMID- 26283223 TI - Perceptions of focused prenatal care among women attending two tertiary centers in Nigeria. AB - OBJECTIVE: To determine women's perceptions and expectations of focused prenatal care visits. METHODS: The present questionnaire-based, cross-sectional survey was performed among pregnant women in their third trimester attending two tertiary health centers in southern Nigeria between January and March 2012. Obstetric data, histories, and information on preferences for prenatal visits were obtained using questionnaires. RESULTS: A total of 353 questionnaires were appropriately completed. Among 277 participants who stated a preference for the number of prenatal care visits, 241 (87.0%) reported a preference of more than four. Among 203 parous women, 132 (65.0%) had no previous negative obstetric experience. Only previous stillbirth (odds ratio [OR] 2.67, 95% confidence interval [CI] 1.05 6.77; P = 0.039) among multiparous women, and HIV/AIDS (OR 0.27, 95% CI 0.06 1.17; P = 0.048) among all women were significantly associated with a preference for more prenatal visits. CONCLUSION: Previous negative obstetric experiences did not generally affect preference for prenatal visits. However, pregnant women expressed dissatisfaction with a reduced number of visits. PMID- 26283224 TI - Prevalence of and risk factors for bacterial vaginosis among women of reproductive age attending cervical screening in southeastern Brazil. AB - OBJECTIVE: To determine the prevalence of and risk factors for bacterial vaginosis. METHODS: A cross-sectional study of women aged 14-54 years attending 18 primary healthcare units in Botucatu, Brazil, for cervical screening was undertaken between September 1, 2012, and January 31, 2013. Data on sociodemographics, sexual behavior, and medical history were obtained by interview. Vaginal swabs were taken to classify the vaginal flora according to the Nugent scoring system. Candida sp. hyphae and infection by Trichomonas vaginalis were also evaluated by microscopy and culture, respectively. Stepwise logistic regression analysis was performed to identify risk factors independently associated with bacterial vaginosis. RESULTS: Among 1519 women included in analyses, 457 (30.1%) had bacterial vaginosis. Variables independently associated with bacterial vaginosis were a single marital status (OR 1.4; 95%CI 1.1-1.8), partner infidelity (OR 1.5; 95%CI 1.2-1.9), abnormal discharge in the previous year (OR 1.5; 95%CI 1.2-2.0), and concurrent trichomoniasis (OR 4.1; 95%CI 1.5 11.5). Current use of hormonal contraception (OR 0.7; 95%CI 0.5-0.9), luteal phase of menstrual cycle (OR 0.8; 95%CI 0.6-0.9), higher income (OR 0.8; 95%CI 0.6-0.9), and vaginal candidiasis (OR 0.5; 95%CI 0.3-0.9) all had protective effects. CONCLUSION: The prevalence of bacterial vaginosis in the study population is high. The epidemiological data provide evidence of the sexual transmissibility of bacterial vaginosis. PMID- 26283225 TI - Validation of a novel tool for assessing newborn resuscitation skills among birth attendants trained by the Helping Babies Breathe program. AB - OBJECTIVE: To validate a simplified objective structured clinical examination (OSCE) tool for evaluating the competency of birth attendants in low-resource countries who have been trained in neonatal resuscitation by the Helping Babies Breathe (HBB) program. METHODS: A prospective cross-sectional study of the OSCE tool was conducted among trained birth attendants working at dispensaries, health centers, or hospitals in five regions of Tanzania between October 1, 2013, and May 1, 2014. A 13-item checklist was used to assess clinical competency in a simulated newborn resuscitation scenario. The OSCE tool was simultaneously administered by HBB trainers and experienced external evaluators. Paired results were compared using the Cohen kappa value to measure inter-rater reliability. Participant performance was rated by health cadre, region, and facility type. RESULTS: Inter-rater reliability was moderate (kappa = 0.41-0.60) or substantial (kappa = 0.61-0.80) for eight of the OSCE items; agreement was fair (kappa = 0.21 0.41) for the remaining five items. The best OSCE performances were recorded among nurses and providers from facilities with high annual birth volumes. CONCLUSION: The simplified OSCE tool could facilitate efficient implementation of national-level HBB programs. Limitations in inter-rater reliability might be improved through additional training. PMID- 26283226 TI - Patterns of fetal growth in an Asian Indian cohort in the USA. AB - OBJECTIVE: To determine whether a greater proportion of fetuses in an Asian Indian cohort are classified as small for gestational age than would be expected from a normally distributed population. METHODS: A retrospective analysis of fetal growth pattern and neonatal outcome was conducted among Asian Indian women who were referred to a maternal-fetal medicine center in Park Ridge, IL, USA, for evaluation of fetal growth between January 1, 2012, and December 31, 2013. The primary outcome was an abdominal circumference or estimated weight of lower than the 10th percentile for gestational age according to the Hadlock formula. RESULTS: Overall, 207 women and 210 fetuses were included. Forty-eight (22.9%) fetuses had an abdominal circumference lower than the 10th percentile. The total number of neonates classified as small for gestational age at delivery was 22 (10.5%), a value indicative of a normally distributed population. CONCLUSION: Fetal size was smaller than expected among the present Asian Indian cohort, but most neonates were classified as appropriate for gestational age at birth. Population specific growth curves are needed to improve assessment of fetal growth. PMID- 26283222 TI - Anopheles stephensi p38 MAPK signaling regulates innate immunity and bioenergetics during Plasmodium falciparum infection. AB - BACKGROUND: Fruit flies and mammals protect themselves against infection by mounting immune and metabolic responses that must be balanced against the metabolic needs of the pathogens. In this context, p38 mitogen-activated protein kinase (MAPK)-dependent signaling is critical to regulating both innate immunity and metabolism during infection. Accordingly, we asked to what extent the Asian malaria mosquito Anopheles stephensi utilizes p38 MAPK signaling during infection with the human malaria parasite Plasmodium falciparum. METHODS: A. stephensi p38 MAPK (AsP38 MAPK) was identified and patterns of signaling in vitro and in vivo (midgut) were analyzed using phospho-specific antibodies and small molecule inhibitors. Functional effects of AsP38 MAPK inhibition were assessed using P. falciparum infection, quantitative real-time PCR, assays for reactive oxygen species and survivorship under oxidative stress, proteomics, and biochemical analyses. RESULTS: The genome of A. stephensi encodes a single p38 MAPK that is activated in the midgut in response to parasite infection. Inhibition of AsP38 MAPK signaling significantly reduced P. falciparum sporogonic development. This phenotype was associated with AsP38 MAPK regulation of mitochondrial physiology and stress responses in the midgut epithelium, a tissue critical for parasite development. Specifically, inhibition of AsP38 MAPK resulted in reduction in mosquito protein synthesis machinery, a shift in glucose metabolism, reduced mitochondrial metabolism, enhanced production of mitochondrial reactive oxygen species, induction of an array of anti-parasite effector genes, and decreased resistance to oxidative stress-mediated damage. Hence, P. falciparum-induced activation of AsP38 MAPK in the midgut facilitates parasite infection through a combination of reduced anti-parasite immune defenses and enhanced host protein synthesis and bioenergetics to minimize the impact of infection on the host and to maximize parasite survival, and ultimately, transmission. CONCLUSIONS: These observations suggest that, as in mammals, innate immunity and mitochondrial responses are integrated in mosquitoes and that AsP38 MAPK-dependent signaling facilitates mosquito survival during parasite infection, a fact that may attest to the relatively longer evolutionary relationship of these parasites with their invertebrate compared to their vertebrate hosts. On a practical level, improved understanding of the balances and trade-offs between resistance and metabolism could be leveraged to generate fit, resistant mosquitoes for malaria control. PMID- 26283228 TI - Bio-Distribution, Imaging Protocols and Diagnostic Accuracy of PET with Tracers of Lipogenesis in Imaging Prostate Cancer: a Comparison between 11C-Choline, 18FFluoroethylcholine and 18F-Methylcholine. AB - PET/CT with choline is a diagnostic tool useful for imaging prostate cancer patients. The overall published papers in this field are referred to three variants of the same radiopharmaceutical: 11C-Choline, 18FMethylcholine and 18F Ethylcholine. As no data has been reported on the theoretical differences between these three variants of radiolabeled choline, this study aims to explore the knowledge on the physiological distribution of these three tracers, to compare data of imaging acquisition protocols and to verify the theoretical equivalence in terms of diagnostic accuracy and potential false positive cases that can occur in clinical practice. A literature research about published papers was conducted regarding the physiological distribution, imaging acquisition protocols and diagnostic performance of 11C-choline, 18F-methylcholine and 18F-ethylcholine PET/CT. Minimal differences of the "in vivo" bio-distribution of the variants of radiolabeled choline were registered. Several imaging acquisition protocols were utilized, considering the different half-decay of 11C and 18F and the early urinary excretion of 18F-FECH. The diagnostic accuracy resulted similar for all the tracers, despite an insignificant amount of data for 18F-FECH; however, some pitfalls were documented for all the variants, related to the intrinsic properties of choline as a non-tumour specific tracer. Finally, our clinical experience with the two fluorinated kinds of choline has also been reported describing the "in vivo" bio-distribution with semi-quantitative measurement of Standardised Uptake Value in target organs. The literature suggests these three variants of choline equally useful to be considered for prostate cancer imaging. A standardisation of acquisition protocols for fluorinated choline PET/CT has also been proposed. PMID- 26283227 TI - Suppression of miR-181a attenuates H2O2-induced death of mesenchymal stem cells by maintaining hexokinase II expression. AB - BACKGROUND: Low survival rate of transplanted cells compromises the efficacy of cell therapy. Hexokinase II (HKII) is known to have anti-apoptotic activity through its interaction with mitochondria. The objective was to identify miRNAs targeting HKII and investigate whether miRNA-mediated modulation of HKII could improve the survival of mesenchymal stem cells (MSCs) exposed to H2O2. The expression of HKII in MSCs exposed to H2O2 was evaluated, and HKII-targeting miRNA was screened based on miRNA-target prediction databases. The effect of H2O2 on the expression of the selected HKII-targeting miRNA was examined and the effect of modulation of the selected HKII-targeting miRNA using anti-miRNA on H2O2-induced apoptosis of MSC was evaluated. RESULTS: H2O2 (600 MUM) induced cell death of MSCs and decreased mitochondrial HKII expression. We have identified miR 181a as a HKII-targeting miRNA and H2O2 increased the expression of miR-181a in MSCs. Delivery of anti-miR-181a, which neutralizes endogenous miR-181a, significantly attenuated H2O2-induced decrease of HKII expression and disruption of mitochondrial membrane potential, improving the survival of MSCs exposed to H2O2. CONCLUSIONS: These findings suggest that H2O2-induced up-regulation of miR 181a contributes to the cell death of MSCs by down-regulating HKII. Neutralizing miR-181a can be an effective way to prime MSCs for transplantation into ischemic tissues. PMID- 26283230 TI - Evaluation of the wound healing property of Commiphora guidottii Chiov. ex. Guid. AB - BACKGROUND: The traditional use of the oleo-gum-resin of Commiphora guidottii Chiov. ex. Guid., which is commonly called scented myrrh, for topical treatment of wound is well documented. The major objective of the present study was to investigate the essential oil and resin obtained from C. guidottii for their potential wound healing properties. Due to their influence on the wound healing process, the anti-inflammatory and antimicrobial activities of scented myrrh have also been investigated. METHODS: Powdered oleo-gum-resin of C. guidottii was steam-distilled to obtain essential oil, and the resin was extracted from the marc with MeOH and filtered. The TLC fingerprint profile of the resin has been recorded by using silica gel GF254 as stationary phase. The essential oil components were identified and quantified by GC-MS. Ointments prepared from the essential oil (4% v/w) and the resin (5% w/w) were used for wound healing activity tests. Toxicity of the formulated ointments was investigated according to Draize skin irritation test. Acute anti-inflammatory effect in mice was evaluated using carrageenan induced mouse hind paw oedema model. Antimicrobial activity tests were carried out using disk diffusion and broth dilution techniques against 21 pathogenic bacterial and 4 fungal strains. RESULTS: Ointment formulations of both the oil and resin were found to be non-irritant at the concentrations used and showed significant (p<0.05-0.001) increase in wound contraction rate, shorter epithelization time and higher skin breaking strength as compared to the negative control. Overall, the antibacterial and antifungal activities of the oil and resin were comparable with the standard antibiotics ciprofloxacin and griseofulvin, respectively. CONCLUSION: The results confirm that scented myrrh possesses genuine wound healing activity supporting the traditional use of the plant. PMID- 26283229 TI - Development of a text-messaging intervention to improve treatment adherence and post-treatment review of children with uncomplicated malaria in western Kenya. AB - BACKGROUND: Patients' low adherence to artemisinin-based combination therapy has been reported in areas of Kenya bordering the Lake Victoria region, where the burden of malaria remains high. A randomized controlled trial is underway to determine the efficacy of short message service (SMS) text reminders on adherence to artemether-lumefantrine and post-treatment review of children under the age of five. This paper reports on the iterative process of intervention and delivery system development. METHODS: An intervention development workshop involving the research team and other stakeholders was held to determine the content of the text messages. Three focus group discussions were conducted to test caregivers' understanding of the messages developed during the workshop. The tested messages were refined and incorporated into an automated SMS distribution system and piloted with 20 caregivers drawn from facilities neighbouring the study sites. The automated SMS distribution system was repeatedly refined following the pilot and implemented at the start of the trial. RESULTS: The content of SMS messages underwent major revisions following the focus group discussions. Technical terms and abbreviations were replaced with simplified general terms. Message sign-off was modified to reflect the name of health facility, removing references to health workers. Day 3 post-treatment review visit reminder was modified to state the purpose of the visit while wording 'day 28' was added to the last post treatment review visit reminder to help the caregiver recall the appointment date. The unscheduled visit prompt was modified to reflect flexibility and practicality of taking the child back to the facility if unwell. Reception of SMS reminders during the pilot was low with only 169/240 (70%) of scheduled messages delivered to the caregivers. The automated distribution system underwent major refinement and repeated testing following the pilot until effective delivery of all scheduled messages was achieved and sustained over a period of 3 months. CONCLUSIONS: Text message interventions should be carefully developed, tested and refined before implementation to ensure they are written in the most appropriate way for their target population. SMS distribution systems should be rigorously tested to ensure efficient delivery of the messages before they are deployed. PMID- 26283231 TI - Construction of a high-density genetic map using specific length amplified fragment markers and identification of a quantitative trait locus for anthracnose resistance in walnut (Juglans regia L.). AB - BACKGROUND: Walnut (Juglans regia, 2n = 32, approximately 606 Mb per 1C genome) is an economically important tree crop. Resistance to anthracnose, caused by Colletotrichum gloeosporioides, is a major objective of walnut genetic improvement in China. The recently developed specific length amplified fragment sequencing (SLAF-seq) is an efficient strategy that can obtain large numbers of markers with sufficient sequence information to construct high-density genetic maps and permits detection of quantitative trait loci (QTLs) for molecular breeding. RESULTS: SLAF-seq generated 161.64 M paired-end reads. 153,820 SLAF markers were obtained, of which 49,174 were polymorphic. 13,635 polymorphic markers were sorted into five segregation types and 2,577 markers of them were used to construct genetic linkage maps: 2,395 of these fell into 16 linkage groups (LGs) for the female map, 448 markers for the male map, and 2,577 markers for the integrated map. Taking into account the size of all LGs, the marker coverage was 2,664.36 cM for the female map, 1,305.58 cM for the male map, and 2,457.82 cM for the integrated map. The average intervals between two adjacent mapped markers were 1.11 cM, 2.91 cM and 0.95 cM for three maps, respectively. 'SNP_only' markers accounted for 89.25% of the markers on the integrated map. Mapping markers contained 5,043 single nucleotide polymorphisms (SNPs) loci, which corresponded to two SNP loci per SLAF marker. According to the integrated map, we used interval mapping (Logarithm of odds, LOD > 3.0) to detect our quantitative trait. One QTL was detected for anthracnose resistance. The interval of this QTL ranged from 165.51 cM to 176.33 cM on LG14, and ten markers in this interval that were above the threshold value were considered to be linked markers to the anthracnose resistance trait. The phenotypic variance explained by each marker ranged from 16.2 to 19.9%, and their LOD scores varied from 3.22 to 4.04. CONCLUSIONS: High-density genetic maps for walnut containing 16 LGs were constructed using the SLAF-seq method with an F1 population. One QTL for walnut anthracnose resistance was identified based on the map. The results will aid molecular marker-assisted breeding and walnut resistance genes identification. PMID- 26283232 TI - Perspectives of obese children and their parents on lifestyle behavior change: a qualitative study. AB - BACKGROUND: In order to improve and optimize future behavioral family lifestyle intervention programs, more information on the perceptions of obese children and their parents of these programs is needed. As such, the aim of this qualitative study is 1) to explore the expectations of obese children and their parents in relation to lifestyle interventions; 2) to identify barriers to making lifestyle changes that parents and children face within their social context (within the family, at school and amongst friends and peers) as well as the things that facilitate these changes and 3) to identify the needs of obese children and their parents in the context of a lifestyle intervention. METHODS: A qualitative study using semi-structured interviews was conducted. Interviewees were participants in a lifestyle intervention program in the Netherlands. RESULTS: Eighteen children (mean age 10 years) and 24 parents were interviewed. The respondents expected to lose weight by being physically active or by eating healthily. Parents struggled with adopting and adhering to new rules and the absence of support of family members. Children struggled with inconsistent parenting and a lack of support from their parents. Bullying experienced at school impeded the children in their ability to make the necessary changes. Support from peers, on the other hand, stimulated their progress. Parents identified the need for the general practitioner to discuss overweight in a non-offensive way and to show an interest in the process of weight loss. CONCLUSIONS: Participants in a lifestyle behavior intervention program benefit from parental support and help from their (extended) family, peers and friends. They would also profit from the sustained involvement of their general practitioner in assisting in the maintenance of lifestyle behavior changes. PMID- 26283234 TI - AcstuA, which encodes an APSES transcription regulator, is involved in conidiation, cephalosporin biosynthesis and cell wall integrity of Acremonium chrysogenum. AB - A transcriptional regulatory gene AcstuA was identified from Acremonium chrysogenum. AcstuA encodes a basic helix-loop-helix protein with similarity to StuA which regulates the core developmental processes of Aspergillus nidulans. Like disruption of stuA in A. nidulans, deficiency of AcstuA blocked the conidiation of A. chrysogenum through severely down-regulating the expression of AcbrlA and AcabaA which encode orthologs of the key fungal developmental regulators BrlA and AbaA. Disruption of AcstuA also drastically reduced cephalosporin production of A. chrysogenum. In agreement, the transcriptions of pcbAB, pbcC, cefD1, cefD2, cefEF and cefG were remarkably decreased in the AcstuA disruption mutant (DeltaAcstuA). In addition to defects in conidiation and cephalosporin biosynthesis, DeltaAcstuA produced abnormal swollen and fragmented hyphal cells during fermentation. The phenotypic alterations of hyphal cells caused by AcstuA deletion were restored by supplementation of NaCl in the medium, indicating that the deficiency of AcstuA has an influence on the cell wall integrity of A. chrysogenum. The transcriptions of two putative mannoprotein encoding genes Acmp2 and Acmp3 significantly reduced in DeltaAcstuA, further indicating that cell wall integrity of the mutant is impaired. These results strongly suggested that AcstuA is involved in conidiation, cephalosporin production, hyphal fragmentation and cell wall integrity in A. chrysogenum. PMID- 26283233 TI - Patellofemoral Pressure Changes After Static and Dynamic Medial Patellofemoral Ligament Reconstructions. AB - BACKGROUND: Reconstructing the medial patellofemoral ligament (MPFL) has become a key procedure for stabilizing the patella. Different techniques to reconstruct the MPFL have been described: static techniques in which the graft is fixed rigidly to the bone or dynamic techniques with soft tissue fixation. Static MPFL reconstruction is most commonly used. However, dynamic reconstruction deforms more easily and presumably functions more like the native MPFL. PURPOSE/HYPOTHESIS: The aim of the study was to evaluate the effect of the different MPFL fixation techniques on patellofemoral pressures compared with the native situation. The hypothesis was that dynamic reconstruction would result in patellofemoral pressures closer to those generated in an intact knee. STUDY DESIGN: Controlled laboratory study. METHODS: Seven fresh-frozen knee specimens were tested in an in vitro knee joint loading apparatus. Tekscan pressure sensitive films fixed to the retropatellar cartilage measured mean patellofemoral and peak pressures, contact area, and location of the center of force (COF) at fixed flexion angles from 0 degrees to 110 degrees . Four different conditions were tested: intact, dynamic, partial dynamic, and static MPFL reconstruction. Data were analyzed using linear mixed models. RESULTS: Static MPFL reconstruction resulted in higher peak and mean pressures from 60 degrees to 110 degrees of flexion (P < .001). There were no differences in pressure between the 2 different dynamic reconstructions and the intact situation (P > .05). The COF in the static reconstruction group moved more medially on the patella from 50 degrees to 110 degrees of flexion compared with the other conditions. The contact area showed no significant differences between the test conditions. CONCLUSION: After static MPFL reconstruction, the patellofemoral pressures in flexion angles from 60 degrees to 110 degrees were 3 to 5 times higher than those in the intact situation. The pressures after dynamic MPFL reconstruction were similar as compared with those in the intact situation, and therefore, dynamic MPFL reconstruction could be a safer option than static reconstruction for stabilizing the patella. CLINICAL RELEVANCE: This study showed that static MPFL reconstruction results in higher patellofemoral pressures and thus enhances the chance of osteoarthritis in the long term, while dynamic reconstruction results in more normal pressures. PMID- 26283235 TI - How 18- and 24-month-old peers divide resources among themselves. AB - Young children are often considered "selfish" with resources because they are reluctant to give up things already in their possession (e.g., as in dictator games). In the current two studies, we presented pairs of 18- and 24-month-old toddlers with various situations involving resources that no one possessed ahead of time. We observed very few instances of individuals attempting to monopolize the resources; rather, the pair peaceably divided them such that each child got something. Equal divisions--even involving one child sacrificing his or her own resources to establish equality-were especially pronounced when children were acting together jointly even in the absence of active collaboration. Children's divisions were also influenced by cues to ownership such as a spatial pre division of resources and resources marked by color (and originally spatially associated with one individual). These results suggest that young children are not selfish, but instead rather generous, with resources when they are dividing them among themselves. PMID- 26283236 TI - A 4-week pilot study with the cannabinoid receptor agonist dronabinol and its effect on metabolic parameters in a randomized trial. AB - PURPOSE: Dronabinol (synthetic Delta(9)- tetrahydrocannabinol) is used in patients with nausea and vomiting from chemotherapy and in AIDS patients for appetite stimulation. Recently, dronabinol was used to successfully treat visceral hypersensitivity causing noncardiac chest pain. With widening uses of this medication, we aim to explore its effects on metabolic parameters in long term dosing and hypothesize that it will not affect major metabolic parameters. METHODS: A double-blind, placebo-controlled, 28-day trial was performed with patients 18 to 75 years old without cardiac disease. Patients had at least 2 weekly episodes of chest pain for the last 3 months and evidence of esophageal hypersensitivity after balloon distention testing. Prior use of pain medication, psychiatric diagnosis, or significant medical comorbidities precluded inclusion in the study. Patients were randomized to receive 5 mg dronabinol or placebo twice daily with metabolic parameters examined before and after the use of medication. FINDINGS: Thirteen patients completed the study (7 with dronabinol [6 women and 1 man] and 6 with placebo [5 women and 1 man]). None of the measured values, including body mass index, HDL, triglycerides, calculated LDL, high sensitivity C-reactive protein, glucose, insulin, leptin, aspartate aminotransferase, alanine aminotransferase, LDH, or non-HDL, differed significantly in either group before or after treatment. In general, treatment with dronabinol coincided with favorable trends in some parameters, although these trends were not statistically significant. IMPLICATIONS: Dronabinol administration does not significantly affect basic metabolic components after a period of 28 days. The implications of these findings are important because dronabinol may be able to be used in patients with metabolic disorders. The favorable trends observed here warrant further exploration into its long-term effects. ClinicalTrials.gov identifier: NCT01598207. PMID- 26283237 TI - Uniform Reduction of Scalar Coupling by Real-Time Homonuclear J-Downscaled NMR. AB - Scalar coupling in proton NMR spectra provides important information for the structural analysis. However, the low resolution due to the resulting signal splitting, together with the rather narrow spectral range of hydrogen, often prevents the extraction of J-coupling information. Here we present a method to achieve real-time homonuclear J-downscaling. Thereby, all J-values are uniformly reduced by an arbitrary scaling factor. In the resulting one-dimensional spectra, signal overlap is reduced, while scalar coupling information is still available. PMID- 26283238 TI - Facial discoid dermatosis: A further case of a novel entity. PMID- 26283239 TI - Caloric restriction in lean and obese strains of laboratory rat: effects on body composition, metabolism, growth and overall health. AB - NEW FINDINGS: What is the central question of this study? How do lean and obese rats respond physiologically to caloric restriction? What is the main finding and its importance? Obese rats show marked benefits compared with lean animals. Reduced body fat is associated with improved longevity with caloric restriction (CR) in rodents. Little is known regarding effects of CR in genetically lean versus obese strains. Long-Evans (LE) and Brown Norway (BN) rats make an ideal comparison for a CR study because the percentage body fat of young adult LE rats is double that of BN rats. Male LE and BN rats were either fed ad libitum (AL) or were calorically restricted to 80 or 90% of their AL weight. The percentages of fat, lean and fluid mass were measured non-invasively at 2- to 4-week intervals. Metabolic rate and respiratory quotient were measured after 3, 6, 9 and 12 months of CR. Overall health was scored monthly. The percentage of fat of the LE strain decreased with CR, whereas the percentage of fat of the BN strain remained above the AL group for several months. The percentage of lean mass increased above the AL for both strains subjected to CR. The percentage of fluid was unaffected by CR. The average metabolic rate over 22 h of the BN rats subjected to CR was reduced, whereas that of LE rats was increased slightly above the AL group. The respiratory quotient of BN rats was decreased with CR. Overall health of the CR LE group was significantly improved compared with that of the AL group, whereas health of the CR BN rats was impaired compared with the AL group. Overall, the lean BN and obese LE strains differ markedly in fat utilization and metabolic response to prolonged CR. There appears to be little benefit of CR in the lean strain. PMID- 26283240 TI - Queer Youth in Family Therapy. AB - Trends in popular belief about same-sex relationships have undergone noteworthy change in the United States over the last decade. Yet this change has been marked by stark polarizations and has occurred at varying rates depending upon regional, community, racial, religious, and individual family context. For queer youth and their families, this cultural transformation has broadened opportunities and created a new set of risks and vulnerabilities. At the same time, youth's increasingly open and playful gender fluidity and sexual identity is complicated by unique intersections of class, race, religion, and immigration. Effective family therapy with queer youth requires practitioner's and treatment models that are sensitive to those who bear the burden of multiple oppressions and the hidden resilience embedded in their layered identities. We present case examples of our model of family therapy which addresses refuge, supports difficult dialogs, and nurtures queerness by looking for hidden resilience in the unique intersections of queer youths' lives. These intersections provide transformational potential for youth, their families and even for family therapists as we are all nurtured and challenged to think more complexly about intersectionality, sexuality, and gender. PMID- 26283241 TI - Infrared Spectra of Protonated Pyrene and Its Neutral Counterpart in Solid para Hydrogen. AB - Protonated polycyclic aromatic hydrocarbons (H(+)PAHs) have been reported to have infrared (IR) bands at wavenumbers near those of unidentified infrared (UIR) emission bands from interstellar objects. We produced 1-C16H11(+) and 1-C16H11 upon electron bombardment during matrix deposition of p-H2 containing pyrene (C16H10) in a small proportion. Intensities of absorption features of 1-C16H11(+) decreased after the matrix was maintained in darkness or irradiated with light at 365 nm, whereas those of 1-C16H11 increased. The observed line wavenumbers and relative intensities of 1-C16H11(+) and 1-C16H11 agree satisfactorily with the scaled vibrational wavenumbers and IR intensities predicted with the B3PW91/6 311++G(2d,2p) method. Our method, being relatively clean with negligible fragmentation, is applicable to larger H(+)PAH; it has the advantages of producing excellent IR spectra covering a broad spectral range with narrow lines and accurate intensities, so that structural identification among various isomers is feasible. PMID- 26283242 TI - Aligned Linear Arrays of Crystalline Nanoparticles. AB - Fabrication of one-dimensional arrays of crystalline nanoparticles with tunable particle size and spacing (down to 20 nm) is demonstrated. The individual nanocrystals are pentagonal prisms, and the arrays are up to 11 MUm in length, with some arrays containing >50 nanocrystals. Precise particle morphology and interparticle spacing can be maintained down the array. The far-field scattering spectra of the arrays show the near-fields of the nanocrystals are coupled. The method is fast and produces precise, well-defined, coupled plasmonic arrays with optical properties that match well to theory. PMID- 26283243 TI - Horizontal Silicon Nanowires with Radial p-n Junctions: A Platform for Unconventional Solar Cells. AB - The silicon p-n junction is the most successful solar energy technology to date, yet it accounts for a marginal percentage of worldwide energy production. To change the status quo, a disruptive technological breakthrough is needed. In this Perspective, we discuss the potential for complex silicon nanowires to serve as a platform for next-generation photovoltaic devices. We review the synthesis, electrical characteristics, and optical properties of core/shell silicon nanowires that are subwavelength in diameter and contain radial p-n junctions. We highlight the unique features of these nanowires, such as optical antenna effects that concentrate light and intense built-in electric fields that enable ultrafast charge-carrier separation. We advocate a paradigm in which nanowires are arranged in periodic horizontal arrays to form ultrathin devices. Unlike conventional planar silicon, nanowire structures provide the flexibility to incorporate multiple semiconductor, dielectric, and metallic materials in a single system, providing the foundation for a disruptive, unconventional solar energy technology. PMID- 26283244 TI - Nanomechanics of Twisted Mono- and Few-Layer Graphene Nanoribbons. AB - Enabled by the technique of objective molecular dynamics, we reveal the unusual mechanics exhibited by nanoscale twisted graphene nanoribbons containing up to seven layers. Unlike in a linear-elastic plate, we find that the deformation practically does not contain contributions associated with in-plane shearing but largely with inhomogeneous stretching and compression of the constituent layers. The whole twisted structure undergoes shortening when no axial force is applied, while the constituent layers store various strain energies, depending on their location. We capture this behavior with a simple model and show that the deviations from the plate model are increasing with the number of layers and width of the ribbon. Our results are especially relevant for the experimental efforts of measuring graphene's shear modulus. PMID- 26283245 TI - Quantum Behavior of Water Molecules Confined to Nanocavities in Gemstones. AB - When water is confined to nanocavities, its quantum mechanical behavior can be revealed by terahertz spectroscopy. We place H2O molecules in the nanopores of a beryl crystal lattice and observe a rich and highly anisotropic set of absorption lines in the terahertz spectral range. Two bands can be identified, which originate from translational and librational motions of the water molecule isolated within the cage; they correspond to the analogous broad bands in liquid water and ice. In the present case of well-defined and highly symmetric nanocavities, the observed fine structure can be explained by macroscopic tunneling of the H2O molecules within a six-fold potential caused by the interaction of the molecule with the cavity walls. PMID- 26283246 TI - Quantum Tunneling Affects Engine Performance. AB - We study the role of individual reaction rates on engine performance, with an emphasis on the contribution of quantum tunneling. It is demonstrated that the effect of quantum tunneling corrections for the reaction HO2 + HO2 = H2O2 + O2 can have a noticeable impact on the performance of a high-fidelity model of a compression-ignition (e.g., diesel) engine, and that an accurate prediction of ignition delay time for the engine model requires an accurate estimation of the tunneling correction for this reaction. The three-dimensional model includes detailed descriptions of the chemistry of a surrogate for a biodiesel fuel, as well as all the features of the engine, such as the liquid fuel spray and turbulence. This study is part of a larger investigation of how the features of the dynamics and potential energy surfaces of key reactions, as well as their reaction rate uncertainties, affect engine performance, and results in these directions are also presented here. PMID- 26283247 TI - Highlighting a Cooling Regime in Liquids under Submillimeter Flows. AB - The shear flow of ordinary liquids is for the first time observed at the submillimeter scale by thermal imaging. We report on microinfrared experiments, showing that liquids as important as water flowing on wetting surfaces produce cooling, while the academic view would foresee heating production. This apparent counterintuitive cooling effect shows that the increase of the internal energy due to the flow can result in different shapes, including a cooling process, before reaching the conventional heating regime at higher shear rates. This unknown property might be interpreted as a transient stretching state of the liquid. Shearing liquids might be a promising alternative compared to conventional endothermic processes (gas expansion or vaporization of a liquid, the Peltier effect, and so forth). PMID- 26283248 TI - CuInSe2 Quantum Dot Solar Cells with High Open-Circuit Voltage. AB - CuInSe2 (CISe) quantum dots (QDs) were synthesized with tunable size from less than 2 to 7 nm diameter. Nanocrystals were made using a secondary phosphine selenide as the Se source, which, compared to tertiary phosphine selenide precursors, was found to provide higher product yields and smaller nanocrystals that elicit quantum confinement with a size-dependent optical gap. Photovoltaic devices fabricated from spray-cast CISe QD films exhibited large, size-dependent, open-circuit voltages, up to 849 mV for absorber films with a 1.46 eV optical gap, suggesting that midgap trapping does not dominate the performance of these CISe QD solar cells. PMID- 26283249 TI - Exploring the Origin of Blue and Ultraviolet Fluorescence in Graphene Oxide. AB - We studied the fluorescence (FL) properties of highly exfoliated graphene oxide (GO) in aqueous solution using continuous-wave and time-resolved FL spectroscopy. The FL spectra of highly exfoliated GO showed two distinct peaks at ~440 (blue) and ~300 nm [ultraviolet (UV)]. The FL of GO in the UV region at ~300 nm was observed for the first time. The average FL lifetimes of the emission peaks at ~440 and ~300 nm are 8-13 and 6-8 ns, respectively. The experimentally observed peak wavelengths of pH-dependent FL, FL excitation spectra, and the FL lifetimes are nearly coincident with those of aromatic compounds bound with oxygen functional groups, which suggests that the FL comes from sp(2) fragments consisting of small numbers of aromatic rings with oxygen functional groups acting as FL centers in the GO. PMID- 26283250 TI - Surprising Molecular Length Dependence in Conduction through a Hybrid Organic Inorganic System. AB - A hybrid device made from gold nanoparticles connected by alkyldithiol molecules of different lengths was produced and its conduction properties were investigated for various lengths of the organic linker molecules. It was found that the conductivity increases with the length of the molecules. The surprising dependence of the conductivity on the molecules' length was explained by a model that takes into account the probability for forming continuous conductive paths for the different molecules. PMID- 26283251 TI - Optically Excited Entangled States in Organic Molecules Illuminate the Dark. AB - We utilize quantum entangled photons to carry out nonlinear optical spectroscopy in organic molecules with an extremely small number of photons. For the first time, fluorescence is reported as a result of entangled photon absorption in organic nonlinear optical molecules. Selectivity of the entangled photon absorption process is also observed and a theoretical model of this process is provided. Through these experiments and theoretical modeling it is found that while some molecules may not have strong classical nonlinear optical properties due to their excitation pathways; these same excitation pathways may enhance the entangled photon processes. It is found that the opposite is also true. Some materials with weak classical nonlinear optical effects may exhibit strong non classical nonlinear optical effects. Our entangled photon fluorescence results provide the first steps in realizing and demonstrating the viability of entangled two-photon microscopy, remote sensing, and optical communications. PMID- 26283252 TI - Excitation Energy Dependence of the Photoluminescence Quantum Yields of Core and Core/Shell Quantum Dots. AB - The photoluminescence (PL) intensity of semiconductor quantum dots (QDs) is routinely monitored to track the chemical and physical properties within a sample or device incorporating the QDs. A dependence of the PL quantum yields (QYs) on the excitation energy could lead to erroneous conclusions but is commonly not considered. We summarize previous evidence and present results from two methodologies that confirm the possibility of a dependence of the PL QYs on the excitation energy. The data presented indicate that PL QYs of CdSe and CdSe/ZnS QDs suspended in toluene are highest for excitation just above the band gap, Eg, of each. The PL QYs decrease with increasing excitation energies up to 1 eV above Eg. The PL intensity decay profiles recorded for these samples at varying emission and excitation energies indicate that the changes in the PL QYs result from the nonradiative relaxation pathways sampled as the charge carriers relax down to the band edge. PMID- 26283253 TI - Carrier Multiplication in Quantum Dots within the Framework of Two Competing Energy Relaxation Mechanisms. AB - The realization of high-yield, low-threshold carrier multiplication (CM) in semiconductor quantum dots (QDs) is a promising step toward third-generation photovoltaics (PV). Recent studies of QD solar cells have shown that CM can indeed produce greater-than-unity quantum efficiencies in photon-to-charge carrier conversion, establishing the relevance of this process to practical PV technologies. While being appreciable, the reported CM yields are still not high enough for a significant increase in the power conversion efficiency over traditional bulk materials. At present, the design of nanomaterials with improved CM is hindered by a poor understanding of the mechanism underlying this process. Here, we present a possible solution to this problem by introducing a model that treats CM as a competition between impact-ionization-like scattering and non-CM energy losses. Importantly, it allows for evaluation of expected CM yields from fairly straightforward measurements of Auger recombination (inverse of CM) and near-band-edge carrier cooling. The validation of this model via a comparative CM study of PbTe, PbSe, and PbS QDs suggests that it indeed represents a predictive capability, which might help in the development of nanomaterials with improved CM performance. PMID- 26283254 TI - Unified Study of Recombination in Polymer:Fullerene Solar Cells Using Transient Absorption and Charge-Extraction Measurements. AB - Recombination in the well-performing bulk heterojunction solar cell blend between the conjugated polymer TQ-1 and the substituted fullerene PCBM has been investigated with pump-probe transient absorption and charge extraction of photogenerated carriers (photo-CELIV). Both methods are shown to generate identical and overlapping data under appropriate experimental conditions. The dominant type of recombination is bimolecular with a rate constant of 7 * 10(-12) cm(-3) s(-1). This recombination rate is shown to be fully consistent with solar cell performance. Deviations from an ideal bimolecular recombination process, in this material system only observable at high pump fluences, are explained with a time-dependent charge-carrier mobility, and the implications of such a behavior for device development are discussed. PMID- 26283255 TI - Dye-Sensitized Solar Cell with Integrated Triplet-Triplet Annihilation Upconversion System. AB - Photon upconversion (UC) by triplet-triplet annihilation (TTA-UC) is employed in order to enhance the response of solar cells to sub-bandgap light. Here, we present the first report of an integrated photovoltaic device, combining a dye sensitized solar cell (DSC) and TTA-UC system. The integrated device displays enhanced current under sub-bandgap illumination, resulting in a figure of merit (FoM) under low concentration (3 suns), which is competitive with the best values recorded to date for nonintegrated systems. Thus, we demonstrate both the compatibility of DSC and TTA-UC and a viable method for device integration. PMID- 26283256 TI - Pressure-Induced Helical Structure of a Peptide Studied by Simulated Tempering Molecular Dynamics Simulations. AB - It is known experimentally that an AK16 peptide forms more alpha-helix structures with increasing pressure while proteins unfold in general. In order to understand this abnormality, molecular dynamics (MD) simulations with the simulated tempering method for the isobaric-isothermal ensemble were performed in a wide pressure range from 1.0 * 10(-4) GPa to 1.4 GPa. From the results of the simulations, it is found that the fraction of the folded state decreases once and increases after that with increasing pressure. The partial molar volume change from the folded state to unfolded state increases monotonically from a negative value to a positive value with pressure. The behavior under high pressure conditions is consistent with the experimental results. The radius of gyration of highly helical structures decreases with increasing pressure, which indicates that the helix structure shrinks with pressure. This is the reason why the fraction of the folded state increases as pressure increases. PMID- 26283257 TI - The Redox Chemistry at the Interface for Retrieving and Brightening the Emission of Doped Semiconductor Nanocrystals. AB - Photo-oxidation of semiconductor quantum dots is the prime concern during their processability, as it often induces nonradiative states and quenches the band edge excitonic emission. Nevertheless, similar effects have been observed for light emitting doped semiconductor nanocrystals, and the dopant emissions are also quenched due to the surface oxidation. This is more pronounced for selenide based host semiconductors. To overcome this, we study the interface chemistry of Cu-doped and Mn-doped ZnSe nanocrystals and report here the retrieving and brightening of the emission from completely quenched months old doped nanocrystals. This has been obtained by treating the doped nanocrystals with appropriate organic thiol ligands which remove the surface oxidative states as well as resist further oxidation of the nanocrystals. Here, we investigate details of the redox chemistry at the interface and study related photophysics in retrieving the dopant emission. PMID- 26283258 TI - Toward the Control of Nonradiative Processes in Semiconductor Nanocrystals. PMID- 26283259 TI - Preparation of Graphene with Graphane Areas of Controlled Hydrogen Isotope Composition on Opposite Sides. AB - Monolayer graphene was prepared on an Ir(111) substrate where it exhibits a 25 * 25 A(2) moire pattern. Molecular hydrogen was dosed first, allowing it to dissociate on open areas of the Ir substrate. The generated H atoms formed an intercalated reservoir that can bind to the graphene subsequently. Next, atomic hydrogen was dosed, which binds to the graphene sheet and also initiates the transfer of H from the Ir substrate to the graphene sheet. The opposite sides of the sheet can be hydrogenated with isotope selectivity, as a sequence of difference isotopes, H or D, can be chosen at will in the preparation procedure. Sum-frequency generation spectra prove that as consequence of the dosing sequence, C-H bonds are predominantly pointing toward the Ir substrate side when H2 is dosed first and alternatively toward the vacuum side when D2 is dosed first. PMID- 26283260 TI - The diversity and host interactions of Propionibacterium acnes bacteriophages on human skin. PMID- 26283261 TI - Portal vein variations in 1000 patients: surgical and radiological importance. AB - OBJECTIVE: The purpose of the study was to evaluate the spectrum and incidence of intrahepatic portal vein (PV) variations on triphasic abdomen multidetector CT (MDCT) and to discuss the surgical and radiological implications. METHODS: A retrospective review of 1000 triphasic MDCT abdomen scans was performed in patients sent for various liver and other abdominal pathologies between January 2014 and August 2014. A total of 967 patients (N = 967) were included in the study. The variations in branching pattern of PV were classified according to classification used by Covey et al (Covey AM, Brody LA, Getrajdman GI, Sofocleous CT, Brown KT. Incidence, patterns, and clinical relevance of variant portal vein anatomy. AJR Am J Roentgenol 2004; 183: 1055-64) and Koc et al (Koc Z, Oguzkurt L, Ulusan S. Portal vein variations: clinical implications and frequencies in routine abdominal CT. Diagn Interv Radiol 2007; 13: 75-80). RESULTS: Normal anatomy (Type I) was seen in 773 patients (79.94%) out of 967 patients in our study. Trifurcation (Type II) anomaly was seen in 66 (6.83%) of cases. Right posterior vein as first branch of main PV (Type III) anomaly was seen in 48 (4.96%) of cases. Type IV anomaly and Type V anomaly was seen in 26 (2.69%) and 13 (1.34%) cases, respectively. 19 cases showed other types of variations. CONCLUSION: Variations in the hepatic PV branching patterns are commonly seen that are similar to variations in hepatic artery and biliary anatomy. Knowledge of these variations is extremely important for transplant surgeons and intervention radiologists. ADVANCES IN KNOWLEDGE: Awareness of the variations in PV branching patterns is essential for intervention radiologists and vascular surgeons and avoids major catastrophic events. PMID- 26283262 TI - Prognostic value of 24-h ABPM in acute ischemic stroke for short-, medium-, and long-term outcome: a systematic review and meta-analysis. AB - BACKGROUND: The association of blood pressure levels during the acute phase of ischemic stroke with outcome remains controversial. AIMS: The objective of this systematic review is to assess the predictive value for stroke outcome assessed by the modified Rankin scale score of systolic and diastolic blood pressure, measured by ambulatory blood pressure monitoring methods during the acute phase of ischemic stroke, compared with the values of casually derived blood pressure measurement on admission. METHODS: We searched for studies with patients admitted within 24 h of stroke onset, and who had ambulatory blood pressure monitoring during the first 24 h of admission. We identified studies that reported blood pressure in those with good outcome and in those with poor outcome at end of follow-up, and performed a meta-analysis of the effect of mean blood pressure on outcome. RESULTS: High systolic and diastolic blood pressure levels derived with ambulatory blood pressure monitoring were associated with poor short-, medium-, and long-term outcome, but the same was not found for casual blood pressure measurements. An increase in systolic blood pressure of 9.1 mmHg (95% confidence interval: 6.6-11.6, P < 0.001; I(2) = 9%) and an increase in diastolic blood pressure of 2.3 mmHg (95% confidence interval: 0.8-3.7, P = 0.002; I(2) = 0%) were associated with poor outcome. CONCLUSIONS: Higher systolic and diastolic blood pressure levels derived with ambulatory blood pressure monitoring were associated with poor outcome. The same was not found for higher casual blood pressure measurements on admission, and it is possible that ambulatory blood pressure monitoring conveys better prognostic information. PMID- 26283263 TI - Monte Carlo optimization for site selection of new chemical plants. AB - Geographic distribution of chemical manufacturing sites has significant impact on the business sustainability of industrial development and regional environmental sustainability as well. The common site selection rules have included the evaluation of the air quality impact of a newly constructed chemical manufacturing site to surrounding communities. In order to achieve this target, the simultaneous consideration should cover the regional background air-quality information, the emissions of new manufacturing site, and statistical pattern of local meteorological conditions. According to the above information, the risk assessment can be conducted for the potential air-quality impacts from candidate locations of a new chemical manufacturing site, and thus the optimization of the final site selection can be achieved by minimizing its air-quality impacts. This paper has provided a systematic methodology for the above purpose. There are total two stages of modeling and optimization work: i) Monte Carlo simulation for the purpose to identify background pollutant concentration based on currently existing emission sources and regional statistical meteorological conditions; and ii) multi-objective (simultaneous minimization of both peak pollutant concentration and standard deviation of pollutant concentration spatial distribution at air-quality concern regions) Monte Carlo optimization for optimal location selection of new chemical manufacturing sites according to their design data of potential emission. This study can be helpful to both determination of the potential air-quality impact for geographic distribution of multiple chemical plants with respect to regional statistical meteorological conditions, and the identification of an optimal site for each new chemical manufacturing site with the minimal environment impact to surrounding communities. The efficacy of the developed methodology has been demonstrated through the case studies. PMID- 26283264 TI - Enhanced sensitization to animal, interpersonal, and intergroup fear-relevant stimuli (but no evidence for selective one-trial fear learning). AB - Selective sensitization has been proposed as an alternative explanation for enhanced responding to animal fear-relevant stimuli--snakes and spiders--during extinction of Pavlovian fear conditioning. The current study sought to replicate the phenomenon using a shock workup procedure as the sensitizing manipulation and to extend it to interpersonal and intergroup fear-relevant stimuli--angry faces and other-race faces. Assessment of selective sensitization was followed by a one trial fear learning procedure. Selective sensitization, larger electrodermal responses to fear-relevant than to control stimuli after sensitization, or a larger increase in electrodermal responding to fear-relevant than to control stimuli after sensitization was observed across stimulus domains. However, the one-trial fear learning procedure failed to provide evidence for enhanced fear conditioning to fear-relevant stimuli. One-trial fear learning was either absent or present for fear-relevant and nonfear-relevant stimuli. The current study confirms that electrodermal responses to fear-relevant stimuli across stimulus domains are subject to selective sensitization. PMID- 26283265 TI - Mechanism, diagnosis, and treatment of outflow tract tachycardia. AB - Idiopathic ventricular arrhythmia is a generic term for a spectrum of arrhythmias that occur in the absence of structural heart disease or ion channelopathy. These arrhythmias include monomorphic premature ventricular contractions (PVCs), nonsustained monomorphic ventricular tachycardia (VT), and sustained VT. Most idiopathic ventricular arrhythmias originate from the right and left ventricular outflow tracts and include sites accessed from the aortic sinuses of Valsalva. Outflow tract arrhythmia is identified by an electrocardiographic pattern consistent with a left bundle branch block inferior axis morphology. Characteristically, outflow tract VT is caused by cAMP-mediated triggered activity, and is terminated by administration of adenosine. Outflow tract arrhythmias are focal and, therefore, are readily amenable to definitive treatment with catheter-based radiofrequency ablation. Although arrhythmia might be associated with reversible PVC-mediated cardiomyopathy, and infrequently with PVC-induced polymorphic VT or ventricular fibrillation, prognosis is generally favourable. PMID- 26283266 TI - Device therapy. Artificical heart uses bioprosthetics to avoid thromboembolic complications. PMID- 26283267 TI - Gene therapy. Inhibiting apoC-III synthesis in patients with hypertriglyceridaemia. PMID- 26283268 TI - Atrial fibrillation. Risk of systemic emboli in AF. PMID- 26283271 TI - "Cutting the wire" as a troubleshooter for a Dormia basket impacted in the common bile duct. PMID- 26283269 TI - Switching P2Y12-receptor inhibitors in patients with coronary artery disease. AB - Dual antiplatelet therapy--the combination of aspirin and a P2Y12-receptor inhibitor--is the cornerstone of treatment of patients with acute coronary syndromes (ACS) and of those undergoing percutaneous coronary intervention. Prasugrel and ticagrelor have more prompt, potent, and predictable antiplatelet effects than those of clopidogrel, and result in reduced ischaemic outcomes in patients with ACS, albeit at the expense of an increased risk of bleeding. However, clopidogrel is still very commonly used. Switching between oral P2Y12 inhibiting therapies occurs very frequently in clinical practice for a variety of reasons, which raises the question of which switching approaches are preferable. In 2015, cangrelor (an intravenous P2Y12-receptor inhibitor) was approved for clinical use, which adds to the conundrum of how to switch between intravenous and oral therapies. Differences in the pharmacology of P2Y12-receptor inhibitors, such as their binding sites (competitive or noncompetitive), half-life, and speed of onset and offset of action, are important factors that might lead to drug interactions when switching between agents. In this Review, we provide an overview of the literature on switching antiplatelet treatment strategies with P2Y12-receptor inhibitors, and discuss practical considerations for switching therapies in the acute and chronic phases of disease presentation. PMID- 26283270 TI - Histone acetylation regulates prostate ductal morphogenesis through a bone morphogenetic protein-dependent mechanism. AB - BACKGROUND: Epigenetic factors influence stem cell function and other developmental events but their role in prostate morphogenesis is not completely known. We tested the hypothesis that histone deacetylase (HDAC) activity is required for prostate morphogenesis. RESULTS: We identified the presence of class I nuclear HDACs in the mouse urogenital sinus (UGS) during prostate development and found that Hdac 2 mRNA abundance diminishes as development proceeds which is especially evident in prostatic epithelium. Blockade of HDACs with the inhibitor trichostatin A (TSA) decreased the number of prostatic buds formed in UGS explant cultures but not the number of buds undergoing branching morphogenesis. In the latter, TSA promoted an extensive branching phenotype that was reversed by exogenous NOGGIN protein, which functions as a bone morphogenetic protein (BMP) inhibitor. TSA also increased Bmp2 promoter H3K27ac abundance, Bmp2 and Bmp4 mRNA abundance, and the percentage of epithelial cells marked by BMP-responsive phosphorylated SMAD1/5/8 protein. TSA exposed UGS explants grafted under the kidney capsule of untreated host mice for continued development achieved a smaller size without an obvious difference in glandular histology compared with control treated grafts. CONCLUSIONS: These results are consistent with an active role for HDACs in shaping prostate morphogenesis by regulating Bmp abundance. PMID- 26283272 TI - A newly modified access balloon catheter for direct peroral cholangioscopy by using an ultraslim upper endoscope (with videos). AB - BACKGROUND AND AIMS: Direct peroral cholangioscopy (POC) by using an ultraslim upper endoscope has been increasingly applied for diagnosis and treatment of diverse biliary diseases. Recently, an intraductal balloon catheter has been used commonly to guide the flexible ultraslim endoscope. However, accessibility into the bile duct remains a limitation of the procedure. The aim of this study was to evaluate the feasibility and success rate of an intraductal balloon-guided direct POC by using an ultraslim endoscope with a newly modified 5F balloon catheter. METHODS: In total, 36 patients with biliary obstruction were included prospectively for a direct POC by using an ultraslim endoscope with a newly modified intraductal 5F balloon catheter. The main outcome measure was technical success, defined as successful advancement of the ultraslim endoscope into the obstructed segment of the biliary tree or the bifurcation. Secondary outcomes were mean time for the total procedure, intubation into the common bile duct and advancement up to the target site after intubation of the ultraslim endoscope, technical success rates of diagnostic and therapeutic interventions, and adverse events. RESULTS: The intraductal balloon-guided direct POC using a newly modified 5F balloon catheter was completed successfully in 35 of 36 patients (97.2%). The mean times for total procedure, intubation into the distal common bile duct, and advancement up to the obstructed bile duct segment were 27.3 +/- 7.2, 2.2 +/- 0.5, and 0.8 +/- 0.4 minutes, respectively. In total, 49 interventions were performed in 35 patients, excluding 1 patient in whom we failed to perform direct POC. Technical success of the interventions was achieved with 44 of 49 procedures (89.8%). No adverse events, including cholangitis, were observed. CONCLUSIONS: A newly modified 5F balloon catheter seemed to facilitate performing intraductal balloon-guided direct POC for direct visual examination of the bile duct in patients with biliary obstruction. Continued development of endoscopes and accessories are expected to further improve the performance of direct POC. PMID- 26283273 TI - Management of Barrett's high-grade dysplasia: initial results from a population based national audit. AB - BACKGROUND AND AIMS: Previous studies reported significant variation in the management of patients with Barrett's esophagus. However, these are based on self reported clinical practice. The aim of this study was to examine the management of high-grade dysplasia in Barrett's esophagus in England by using patient-level data and to compare practice with guidelines. METHODS: From April 2012 to March 2013, National Health Service (NHS) trusts in England prospectively collected data on patients newly diagnosed with high-grade dysplasia (HGD) of the esophagus as part of the National Oesophago-Gastric Cancer Audit. Data were collected on patient characteristics, diagnosis and endoscopic findings, treatment planning, and therapy. RESULTS: Between April 2012 and March 2013, NHS trusts reported 465 cases of HGD. Diagnosis was confirmed by a second pathologist in 79.4% of cases (270/340), and 86.0% (374/465) had their treatment planned at a multidisciplinary team meeting. A total of 290 patients (62.4%) were managed endoscopically (frequently with endoscopic resection or radiofrequency ablation), whereas 26 patients (5.6%) had esophagectomy. The proportion of patients managed by surveillance varied by age (P < .001), ranging from 19.5% in patients aged <65 years to 63.8% in patients aged >=85 years. More patients received active treatment if their cases were discussed at a multidisciplinary meeting (73.5% vs 44.3%; P < .001) or managed at higher-volume trusts (87.8% vs 55.4%; P < .001). CONCLUSIONS: There was marked variation in the management of HGD across England, with a third of patients receiving no active treatment. Patients discussed at a specialist multidisciplinary meeting or managed in high-volume trusts were more likely to receive active treatment. PMID- 26283274 TI - Epilogue: The future of Laron syndrome - The need for changes. PMID- 26283275 TI - Improved glycemic control due to sitagliptin is not related to cortisol or the surrogate marker IGFBP-1 for hepatic insulin sensitivity. AB - IMPORTANCE: Elevated cortisol levels and dysregulated insulin-like growth factor binding protein-1 (IGFBP-1; a marker of hepatic insulin sensitivity) are both related to insulin resistance and glucose abnormalities. It is unknown whether improvement in these parameters is related to improved glucose metabolism during treatment with sitagliptin. OBJECTIVE: To determine whether improved insulin sensitivity and beta-cell function during treatment with sitagliptin is related to lower cortisol levels and/or improved regulation of IGFBP-1 in patients with recent acute coronary syndrome (ACS) and newly discovered glucose abnormalities. DESIGN: Samples were taken from The BEta-cell function in Glucose abnormalities and Acute Myocardial Infarction (BEGAMI) trial, a double-blinded, placebo controlled randomized clinical trial on the efficacy and safety of sitagliptin for patients with ACS and newly discovered glucose abnormalities. SETTING: Cardiology departments (cardiac ICU and outpatient clinic) in two hospitals in Stockholm, Sweden. PARTICIPANTS: Subjects hospitalized (or recently hospitalized) for ACS, in whom an oral glucose tolerance test revealed previously unknown glucose abnormalities. INTERVENTIONS: Subjects were randomized to sitagliptin 100mg once daily (n=34) or placebo (n=37) for twelve weeks. Oral glucose tolerance test (OGTT) and randomization occurred after stabilization median 7 days after ACS. MAIN OUTCOMES AND MEASURES: Fasting serum cortisol and IGFBP-1 were analyzed before OGTT, around 8a.m., and after at 10a.m. The latter time point was chosen as the spread in cortisol levels around is small then, allowing improved chances to detect differences between groups. RESULTS: Glucose tolerance and insulin sensitivity improved in both groups, while HbA1c and indices of beta cell function improved only in the sitagliptin group as reported previously. Both groups displayed decreased cortisol levels around 10a.m. (from 338+/-21 to 278+/ 14 nmol/L, p=0.038, in the sitagliptin group; from 343+/-17 to 302+/-15 nmol/L, p=0.017, in the placebo group), and improved correlation between fasting log IGFBP-1 and insulin. CONCLUSIONS AND RELEVANCE: These findings suggest that a stress-related elevation in cortisol may have negative impact on glucose tolerance in patients with recent ACS. However, improved glycemic control with sitagliptin does not appear to be related to changes in cortisol levels or hepatic insulin sensitivity as assessed by IGFBP-1. PMID- 26283277 TI - Effects of beta-hydroxybutyricacid on the synthesis and assembly of very low density lipoprotein in bovine hepatocytes in vitro. AB - beta-Hydroxybutyricacid (BHBA) is an important metabolite that involved in the development of ketosis and fatty liver in dairy cows. Dairy cows with fatty liver displayed high blood concentration of BHBA and very low-density lipoprotein (VLDL) assembly. The effects of BHBA on VLDL synthesis and assembly in hepatocytes of cows were unclear. In this study, bovine hepatocytes were cultured and treated with different concentrations of BHBA. We found that BHBA treatment upregulated the mRNA and protein levels of apolipoprotein B100 (ApoB 100), apolipoprotein E (ApoE) and microsomal triglyceride transfer protein (MTTP) and showed in a firstly increased and then decreased trend. Meanwhile, the mRNA and protein levels of LDLR showed in a reverse trend. Consequently, VLDL content was significantly increased in medium-dose BHBA treatment group, while decreased in high-dose group. These results indicate that the effects of BHBA on the VLDL synthesis showed in a dose-dependent manner that low levels of BHBA increase VLDL synthesis and high levels of BHBA decrease VLDL synthesis. PMID- 26283276 TI - Utility of whole-exome sequencing for those near the end of the diagnostic odyssey: time to address gaps in care. AB - An accurate diagnosis is an integral component of patient care for children with rare genetic disease. Recent advances in sequencing, in particular whole-exome sequencing (WES), are identifying the genetic basis of disease for 25-40% of patients. The diagnostic rate is probably influenced by when in the diagnostic process WES is used. The Finding Of Rare Disease GEnes (FORGE) Canada project was a nation-wide effort to identify mutations for childhood-onset disorders using WES. Most children enrolled in the FORGE project were toward the end of the diagnostic odyssey. The two primary outcomes of FORGE were novel gene discovery and the identification of mutations in genes known to cause disease. In the latter instance, WES identified mutations in known disease genes for 105 of 362 families studied (29%), thereby informing the impact of WES in the setting of the diagnostic odyssey. Our analysis of this dataset showed that these known disease genes were not identified prior to WES enrollment for two key reasons: genetic heterogeneity associated with a clinical diagnosis and atypical presentation of known, clinically recognized diseases. What is becoming increasingly clear is that WES will be paradigm altering for patients and families with rare genetic diseases. PMID- 26283278 TI - Silk fibroin/copolymer composite hydrogels for the controlled and sustained release of hydrophobic/hydrophilic drugs. AB - In the present study, a composite system for the controlled and sustained release of hydrophobic/hydrophilic drugs is described. Composite hydrogels were prepared by blending silk fibroin (SF) with PLA-PEG-PLA copolymer under mild aqueous condition. Aspirin and indomethacin were incorporated into SF/Copolymer hydrogels as two model drugs with different water-solubility. The degradation of composite hydrogels during the drug release was mainly caused by the hydrolysis of copolymers. SF with stable beta-sheet-rich structure was not easily degraded which maintained the mechanical integrity of composite hydrogel. The hydrophobic/hydrophilic interactions of copolymers with model drugs would significantly alter the morphological features of composite hydrogels. Various parameters such as drug load, concentration ratio, and composition of copolymer were considered in vitro drug release. Aspirin as a hydrophilic drug could be controlled release from composite hydrogel at a constant rate for 5 days. Its release was mainly driven by diffusion-based mechanism. Hydrophobic indomethacin could be encapsulated in copolymer nanoparticles distributing in the composite hydrogel. Its sustained release was mainly degradation controlled which could last up to two weeks. SF/Copolymer hydrogel has potential as a useful composite system widely applying for controlled and sustained release of various drugs. PMID- 26283279 TI - Linking flowability and granulometry of lactose powders. AB - The flowing properties of 10 lactose powders commonly used in pharmaceutical industries have been analyzed with three recently improved measurement methods. The first method is based on the heap shape measurement. This straightforward measurement method provides two physical parameters (angle of repose alphar and static cohesive index sigmar) allowing to make a first screening of the powder properties. The second method allows to estimate the rheological properties of a powder by analyzing the powder flow in a rotating drum. This more advanced method gives a large set of physical parameters (flowing angle alphaf, dynamic cohesive index sigmaf, angle of first avalanche alphaa and powder aeration %ae) leading to deeper interpretations. The third method is an improvement of the classical bulk and tapped density measurements. In addition to the improvement of the measurement precision, the densification dynamics of the powder bulk submitted to taps is analyzed. The link between the macroscopic physical parameters obtained with these methods and the powder granulometry is analyzed. Moreover, the correlations between the different flowability indexes are discussed. Finally, the link between grain shape and flowability is discussed qualitatively. PMID- 26283280 TI - Development and ex vivo evaluation of 5-aminolevulinic acid-loaded niosomal formulations for topical photodynamic therapy. AB - The objective of this study was the development of a niosomal formulation for improving skin permeation and penetration of 5-aminolevulinic acid (ALA) in the treatment of skin malignancies by photodynamic therapy (PDT). Different niosomal dispersions were prepared, using two different preparation methods. The effect of addition to a classic formulation, consisting in an equimolar Span 60-cholesterol mixture, of two different edge activators, dicethyl-phosphate (DCP) and sodium cholate (SC), and of the presence of ethanol on the vesicle properties and stability was evaluated. Selected formulations were loaded with the drug and evaluated for physicochemical and stability properties and encapsulation efficiency. Classic and elastic DCP-containing niosomes were the only formulations able to effectively incorporate the drug without instability problems. Ex vivo permeation and penetration studies through excised human skin showed that both the niosomal formulations were significantly more effective in improving ALA skin delivery than the simple aqueous drug solution commonly used in clinical practice, allowing, respectively, an increase of about 80 and 40% of the drug permeated amount and of about 100 and 50% of the drug retained into the skin. These results lead to consider the developed formulations potentially useful for improving ALA bioavailability and therapeutic effectiveness in skin malignancies treatment by topical PDT. PMID- 26283281 TI - Upper critical solution temperature behavior of cinnamic acid and polyethyleneimine mixture and its effect on temperature-dependent release of liposome. AB - The mixture of polyethyleneimine (PEI) and cinnamic acid (CA) in HEPES buffer (pH 7.0) exhibited an upper critical solution temperature in the temperature range of 20-50 degrees C. CA would be electrostatically conjugated with PEI and the PEI CA conjugate is thought to act as a thermo-sensitive polymer. On the optical microscope image of PEI/CA mixture, microparticles were found at 25 degrees C, disappeared when heated to 50 degrees C, and formed again upon cooling to 25 degrees C. PEI-CA conjugate was immobilized on the surface of egg phosphatidylcholine (EPC) liposome by adding PEI to the suspension of liposome incorporating CA. The size and the zeta potential of the liposome markedly increased by cooling the liposomal suspension from 50 degrees C to 20 degrees C. This could be ascribed to the cooling-induced self-assembling property of PEI CA conjugate. The release profile of Rhodamine B base from liposome incorporating CA with PEI was investigated while the liposome suspension of 50 degrees C was exposed to the release medium of 20 degrees C, 30 degrees C, 40 degrees C and 50 degrees C. The release degree was higher at a lower temperature. When exposed to a lower temperature (20 degrees C, 30 degrees C, 40 degrees C), PEI-CA could be self-assembled and change its configuration on the surface of liposome, promoting the release from the liposome. PMID- 26283282 TI - Subjectivity in retinopathy of prematurity screening. PMID- 26283283 TI - Reply: To PMID 25703477. PMID- 26283285 TI - Selection and identification of a bacterial community able to degrade and detoxify m-nitrophenol in continuous biofilm reactors. AB - Nitroaromatics are widely used for industrial purposes and constitute a group of compounds of environmental concern because of their persistence and toxic properties. Biological processes used for decontamination of nitroaromatic polluted sources have then attracted worldwide attention. In the present investigation m-nitrophenol (MNP) biodegradation was studied in batch and continuous reactors. A bacterial community able to degrade the compound was first selected from a polluted freshwater stream and the isolates were identified by the analysis of the 16S rRNA gene sequence. The bacterial community was then used in biodegradation assays. Batch experiments were conducted in a 2L aerobic microfermentor at 28 degrees C and with agitation (200 rpm). The influence of abiotic factors in the biodegradation process in batch reactors, such as initial concentration of the compound and initial pH of the medium, was also studied. Continuous degradation of MNP was performed in an aerobic up-flow fixed-bed biofilm reactor. The biodegradation process was evaluated by determining MNP and ammonium concentrations and chemical oxygen demand (COD). Detoxification was assessed by Vibrio fischeri and Pseudokirchneriella subcapitata toxicity tests. Under batch conditions the bacterial community was able to degrade 0.72 mM of MNP in 32 h, with efficiencies higher than 99.9% and 89.0% of MNP and COD removals respectively and with concomitant release of ammonium. When the initial MNP concentration increased to 1.08 and 1.44 mM MNP the biodegradation process was accomplished in 40 and 44 h, respectively. No biodegradation of the compound was observed at higher concentrations. The community was also able to degrade 0.72 mM of the compound at pH 5, 7 and 9. In the continuous process biodegradation efficiency reached 99.5% and 96.8% of MNP and COD removal respectively. The maximum MNP removal rate was 37.9 gm(-3) day(-1). Toxicity was not detected after the biodegradation process. PMID- 26283286 TI - Toxic effects of magnesium oxide nanoparticles on early developmental and larval stages of zebrafish (Danio rerio). AB - Magnesium oxide nanoparticles (MgONPs) are used in medicine, manufacturing and food industries. Because of their extensive application in our daily lives, environmental exposure to these nanoparticles is inevitable. The present study examined the effects of MgONPs on zebrafish (Danio rerio) early developmental stages. The results showed that, at different concentrations, MgONPs induced cellular apoptosis and intracellular reactive oxygen species. The hatching rate and survival of embryos decreased in a dose dependent manner. The 96-h LC50 value of MgONPs on zebrafish survival was 428 mg/l and the 48-h EC50 value of MgONPs on zebrafish embryo hatching rate was 175 mg/l. Moreover different types of malformation were observed in exposed embryos. The results demonstrate the toxic effects of MgONPs on zebrafish embryos and emphasize the need for further studies. PMID- 26283284 TI - Enzyme replacement in the CSF to treat metachromatic leukodystrophy in mouse model using single intracerebroventricular injection of self-complementary AAV1 vector. AB - Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by a functional deficiency in human arylsulfatase A (hASA). We recently reported that ependymal cells and the choroid plexus are selectively transduced by intracerebroventricular (ICV) injection of adeno-associated virus serotype 1 (AAV1) vector and serve as a biological reservoir for the secretion of lysosomal enzymes into the cerebrospinal fluid (CSF). In the present study, we examined the feasibility of this AAV-mediated gene therapy to treat MLD model mice. Preliminary experiments showed that the hASA level in the CSF after ICV injection of self-complementary (sc) AAV1 was much higher than in mice injected with single stranded AAV1 or scAAV9. However, when 18-week-old MLD mice were treated with ICV injection of scAAV1, the concentration of hASA in the CSF gradually decreased and was not detectable at 12 weeks after injection, probably due to the development of anti-hASA antibodies. As a result, the sulfatide levels in brain tissues of treated MLD mice were only slightly reduced compared with those of untreated MLD mice. These results suggest that this approach is potentially promising for treating MLD, but that controlling the immune response appears to be crucial for long-term expression of therapeutic proteins in the CSF. PMID- 26283287 TI - Phytotoxicity of three plant-based biodiesels, unmodified castor oil, and Diesel fuel to alfalfa (Medicago sativa L.), lettuce (Lactuca sativa L.), radish (Raphanus sativus), and wheatgrass (Triticum aestivum). AB - The wide use of plant-based oils and their derivatives, in particular biodiesel, have increased extensively over the past decade to help alleviate demand for petroleum products and improve the greenhouse gas emissions profile of the transportation sector. Biodiesel is regarded as a clean burning alternative fuel produced from livestock feeds and various vegetable oils. Although in theory these animal and/or plant derived fuels should have less environmental impact in soil based on their simplified composition relative to Diesel, they pose an environmental risk like Diesel at high concentrations when disposed. The aim of the present study was to ascertain the phytotoxicity of three different plant derived biodiesels relative to conventional Diesel. For phytotoxicological analysis, we used seeds of four crop plants, Medicago sativa, Lactuca sativa, Raphanus sativus, and Triticum aestivum to analyze the germination of seeds in contaminated soil samples. The toxicological experiment was conducted with two different soil textures: sandy loam soil and silt loam soil. The studied plant based biodiesels were safflower methyl-ester, castor methyl ester, and castor ethyl-ester. Biodiesel toxicity was more evident at high concentrations, affecting the germination and survival of small-seeded plants to a greater extent. Tolerance of plants to the biodiesels varied between plant species and soil textures. With the exception of R. sativus, all plant species were affected and exhibited some sensitivity to the fuels, such as delayed seedling emergence and slow germination (average=10 days) at high soil concentrations (0.85% for Diesel and 1.76% for the biodiesels). Tolerance of plants to soil contamination had a species-specific nature, and on average, decreased in the following order: Raphanus sativus (0-20%)>Triticum aestivum (10-40%) >= Medicago sativa> Lactuca sativa (80-100%). Thus, we conclude that there is some phytotoxicity associated with plant-based biodiesels. Further, the findings of this study can be useful for selecting the least fuel-tolerant species as a soil contamination bio indicator and for determining the risks of biodiesel contamination. PMID- 26283288 TI - Effect of aqueous media on the copper-ion-mediated phototoxicity of CuO nanoparticles toward green fluorescent protein-expressing Escherichia coli. AB - Quantitative comparison of different aqueous media on the phototoxicity of copper oxide nanoparticles (CuO NPs) is crucial for understanding their ecological effects. In this study, the phototoxicity of CuO NPs toward the green fluorescent protein-expressing Escherichia coli (GFP-E. coli) under UV irradiation (365 nm) was investigated in Luria-Bertani medium (LB), NaCl solution, deionized water (DI) and phosphate-buffered saline (PBS). The phototoxicity of CuO NPs toward GFP E. coli decreased in the order of DI>NaCl>PBS>LB because of different released concentrations of Cu(2+). The 3h released Cu(2+) concentrations by 10mg/L CuO NPs in DI water, NaCl solution, LB medium, and PBS were 1946.3 +/- 75.6, 1242.5 +/- 47.6, 1023.4 +/- 41.2, and 1162.1 +/- 41.9 MUg/L, respectively. Transmission electron microscope and laser scanning confocal microscope images of E. coli exposed to CuO NPs demonstrated that the released Cu(2+) resulted in fragmentation of bacterial cell walls, leakage of intracellular components, and finally death of bacteria in four media after UV light irradiation. In each medium, the bacterial mortality rate logarithmically increased with the releasing concentrations of Cu(2+) by CuO NPs (R(2)>0.90) exposed to 3h UV light. This study highlights the importance of taking into consideration of water chemistry when the phototoxicity of CuO NPs is assessed in nanotoxicity research. PMID- 26283289 TI - Pore-water chemistry explains zinc phytotoxicity in soil. AB - Zinc (Zn) is a widespread soil contaminant arising from a numerous anthropogenic sources. However, adequately predicting toxicity of Zn to ecological receptors remains difficult due to the complexity of soil characteristics. In this study, we examined solid-solution partitioning using pore-water data and toxicity of Zn to cucumber (Cucumis sativus L.) in spiked soils. Pore-water effective concentration (ECx, x=10%, 20% and 50% reduction) values were negatively related to pH, indicating lower Zn pore water concentration were needed to cause phytotoxicity at high pH soils. Total dissolved zinc (Znpw) and free zinc (Zn(2+)) in soil-pore water successfully described 78% and 80.3% of the variation in relative growth (%) in the full dataset. When the complete data set was used (10 soils), the estimated EC50pw was 450 and 79.2 uM for Znpw and Zn(2+), respectively. Total added Zn, soil pore water pH (pHpw) and dissolve organic carbon (DOC) were the best predictors of Znpw and Zn(2+) in pore-water. The EC10 (total loading) values ranged from 179 to 5214 mg/kg, depending on soil type. Only pH measurements in soil were related to ECx total Zn data. The strongest relationship to ECx overall was pHca, although pHw and pHpw were in general related to Zn ECx. Similarly, when a solution-only model was used to predict Zn in shoot, DOC was negatively related to Zn in shoot, indicating a reduction in uptake/ translocation of Zn from solution with increasing DOC. PMID- 26283291 TI - The effects of auditory hallucination symptom management programme for people with schizophrenia: a quasi-experimental design. AB - AIM: To examine the effectiveness of an auditory hallucinatory symptom management programme in patients with chronic schizophrenia. BACKGROUND: Thirty per cent of chronic schizophrenia patients are still disturbed by hallucinations, which influence their psychological and social well-being, even when they take medication regularly. METHOD: Fifty-eight people experiencing schizophrenia with auditory hallucinations from psychiatric inpatient rehabilitation wards in northern Taiwan participated in the study, with 29 in the experimental group and 29 in the control group. The experimental group received an auditory hallucinatory symptom management programme. The auditory hallucinatory symptom management programme involved 60-minute meetings once a week, for a total of 10 meetings. The control group received routine care, which included free recreation for 40 minutes and walking for 20 minutes. The participants completed three self report questionnaires: the Beck Depressive Inventory II, the Beck Anxiety Inventory and the Characteristics of Auditory Hallucinations Questionnaire. Data were collected at baseline, immediately following the intervention and at 3 months and 6 months post intervention. Data collection occurred between March 2010-May 2013. RESULTS: The experimental group showed a non-significant improvement in anxiety symptoms over time. Generalized estimating equations revealed that the experimental group achieved a greater drop in Characteristics of Auditory Hallucinations Questionnaire score than the controls at three and 6 months post intervention. Beck Depressive Inventory II scores in the experimental group (n = 29) had significantly improved in 3 months. CONCLUSION: The auditory hallucinatory symptom management programme seems to be effective in improving auditory hallucinatory symptoms and depressive symptoms in patients with schizophrenia. PMID- 26283290 TI - Mobile Apps for Bipolar Disorder: A Systematic Review of Features and Content Quality. AB - BACKGROUND: With continued increases in smartphone ownership, researchers and clinicians are investigating the use of this technology to enhance the management of chronic illnesses such as bipolar disorder (BD). Smartphones can be used to deliver interventions and psychoeducation, supplement treatment, and enhance therapeutic reach in BD, as apps are cost-effective, accessible, anonymous, and convenient. While the evidence-based development of BD apps is in its infancy, there has been an explosion of publicly available apps. However, the opportunity for mHealth to assist in the self-management of BD is only feasible if apps are of appropriate quality. OBJECTIVE: Our aim was to identify the types of apps currently available for BD in the Google Play and iOS stores and to assess their features and the quality of their content. METHODS: A systematic review framework was applied to the search, screening, and assessment of apps. We searched the Australian Google Play and iOS stores for English-language apps developed for people with BD. The comprehensiveness and quality of information was assessed against core psychoeducation principles and current BD treatment guidelines. Management tools were evaluated with reference to the best-practice resources for the specific area. General app features, and privacy and security were also assessed. RESULTS: Of the 571 apps identified, 82 were included in the review. Of these, 32 apps provided information and the remaining 50 were management tools including screening and assessment (n=10), symptom monitoring (n=35), community support (n=4), and treatment (n=1). Not even a quarter of apps (18/82, 22%) addressed privacy and security by providing a privacy policy. Overall, apps providing information covered a third (4/11, 36%) of the core psychoeducation principles and even fewer (2/13, 15%) best-practice guidelines. Only a third (10/32, 31%) cited their information source. Neither comprehensiveness of psychoeducation information (r=-.11, P=.80) nor adherence to best-practice guidelines (r=-.02, P=.96) were significantly correlated with average user ratings. Symptom monitoring apps generally failed to monitor critical information such as medication (20/35, 57%) and sleep (18/35, 51%), and the majority of self assessment apps did not use validated screening measures (6/10, 60%). CONCLUSIONS: In general, the content of currently available apps for BD is not in line with practice guidelines or established self-management principles. Apps also fail to provide important information to help users assess their quality, with most lacking source citation and a privacy policy. Therefore, both consumers and clinicians should exercise caution with app selection. While mHealth offers great opportunities for the development of quality evidence-based mobile interventions, new frameworks for mobile mental health research are needed to ensure the timely availability of evidence-based apps to the public. PMID- 26283292 TI - Accuracy and Usability of a Self-Administered 6-Minute Walk Test Smartphone Application. AB - BACKGROUND: The 6-minute walk test (6MWT) independently predicts congestive heart failure severity, death, and heart failure hospitalizations, but must be administered in clinic by qualified staff on a premeasured course. As part of the Health eHeart Study, we sought to develop and validate a self-administered 6MWT mobile application (SA-6MWTapp) for independent use at home by patients. METHODS AND RESULTS: We performed a validation study of an SA-6MWTapp in 103 participants. In phase 1 (n=52), we developed a distance-estimation algorithm for the SA-6MWTapp by comparing step counts from an Actigraph and measured distance on a premeasured 6MWT course with step counts and estimated distance obtained simultaneously from our SA-6MWTapp (best estimation algorithm, r=0.89 [95% confidence interval 0.78-0.99]). In phase 2, 32 participants (including those with congestive heart failure and pulmonary hypertension) used the SA-6MWTapp independently in clinic, and the distance estimated by the SA-6MWTapp was compared with the measured distance (r=0.83 [95% confidence interval 0.79-0.92]). In phase 3, 19 patients with congestive heart failure and pulmonary hypertension consecutively enrolled from clinic performed 3.2+/-1 SA-6MWTapp tests per week at home over 2 weeks. Distances estimated from the SA-6MWTapp during home 6MWTs were highly repeatable (coefficient of variation =4.6%) and correlated with in-clinic measured distance (r=0.88 [95% confidence interval 0.87-0.89]). Usability surveys performed during the second (in-clinic) and third (at-home) phases demonstrated that the SA-6MWTapp was simple and easy to use independently. CONCLUSIONS: An SA 6MWTapp is easy to use and yields accurate repeatable measurements in the clinic and at home. PMID- 26283293 TI - Ultrasound detection of pneumonia in febrile children with respiratory distress: a prospective study. AB - To analyse the usefulness of bedside lung ultrasound (LUS) in detecting lung consolidation in a paediatric emergency room (ER) setting, febrile children seen at our ER from 2008 to 2012 with a moderate to severe respiratory distress underwent LUS, chest X-ray (CXR) and laboratory investigations. At first ER assessment, LUS identified a lung consolidation in 207 patients of 222 children enrolled, with a liver-like appearance in 75 (36.2%) and an associated pleural effusion in 36.7% of cases. CXR proved positive in 197 cases, showing a parenchymal consolidation (68.5%) or a focal ground-glass opacity (31.4%). LUS liver-like consolidation was significantly associated with longer duration of fever (p = 0.002), higher neutrophil counts and C-reactive protein (CRP) values (p = 0.015 and p < 0.0001, respectively), and with the discovery of a homogeneous and dense parenchymal consolidation on CXR (p < 0.0001). CONCLUSION: LUS can be adopted by the clinician as a non-invasive bedside tool to expand the physical evaluation of febrile children with respiratory distress. In our study, LUS results appeared not only as reliable as CXR in detecting lung consolidations but also consistent with clinical and laboratory data. WHAT IS KNOWN: The diagnosis of pneumonia is mainly based on physical examination plus radiologic and laboratory evaluation when needed. Although lung ultrasound (LUS) has shown high sensitivity in detecting several pleuropulmonary diseases in adults, its role in the work-up of pneumonia in children is not yet widely recognized. WHAT IS NEW: LUS is confirmed to be a reliable imaging technique for the diagnostic work-up of febrile children with respiratory distress, consistent not only with CXR results as previously reported by others but also with clinical and laboratory data. In the hands of trained clinicians, it may represent a valuable supplemental bedside tool for a rapid evaluation in such circumstances. PMID- 26283294 TI - Sporadic paraganglioma caused by de novo SDHB mutations in a 6-year-old girl. AB - Germline mutations in the succinate dehydrogenase complex subunit B (SDHB) gene (SDHB) cause susceptibility to paragangliomas and pheochromocytomas; however, it is exceedingly rare in childhood and especially in sporadic cases. We report the first Japanese pediatric case of paraganglioma with a de novo mutation in the SDHB gene. A 6-year-old girl with convulsions and hypertension was found to have a paravertebral abdominal tumor. Urinary and blood examinations revealed markedly elevated levels of norepinephrine. Following treatment for hypertension, the tumor was removed completely and histological findings were consistent with paraganglioma. Immunohistochemistry studies demonstrated the absence of SDHB protein expression, indicating an underlying SDH mutation with high probability. Germline mutation analysis of the SDHB gene revealed a heterozygous splice site mutation in intron 4 (C.423 + 1G > A). Subsequently, a second somatic genetic change was confirmed by multiplex ligation-dependent probe amplification (MLPA) analysis, showing that deletion of the wild-type allele resulted in loss of function of SDHB. No germline mutations in SDHB were detected in her parents. CONCLUSION: Genetic testing should be considered for pediatric patients with paragangliomas, even in the absence of familial history, as closer lifelong screening to detect the development of malignancy will be required for patients with SDHB mutations. WHAT IS KNOWN: Most sporadic cases of paraganglioma with SDHB mutations occur between adolescence and adulthood. Screening methods for carriers of SDHB mutations assessing recurrence and detecting developing metastases are yet to be standardized. WHAT IS NEW: The current case of an extra adrenal paraganglioma with a de novo SDHB mutation had an onset at 6 years. We suggest much closer periodical observation for these high-risk children. PMID- 26283295 TI - The impact of anastomotic leakage on oncologic outcomes and the receipt and timing of adjuvant chemotherapy after colorectal cancer surgery. AB - PURPOSES: To evaluate the impact of anastomotic leakage on oncologic outcomes in patients with colorectal cancer. We also evaluated the influence of anastomotic leakage on receipt and commencement time of adjuvant chemotherapy. METHODS: A total of 809 consecutive patients undergoing major resection for colorectal cancer were categorized into leak (n = 33, 4.1%) and non-leak (n = 776, 95.9%) groups. RESULTS: The 5-year local recurrence rates of stage II disease were 0.6% and 20.0% for non-leak and leak groups respectively (p = 0.046), and the equivalent rates for stage III disease were 9.1% and 59.4% respectively (p < 0.001). For stage III disease, receipt of adjuvant therapy was lower in the leak group (63% vs. 87%, p = 0.007) and mean time to initiation of chemotherapy was longer in the leak group (52 days vs. 37 days) but this did not reach statistical significance (p = 0.080). Older age (hazard ratio [HR] = 2.8), advanced TNM classification (HR = 3.6), and anastomotic leakage (HR = 8.9) were adverse risk factors for local recurrence based on multivariate analysis. CONCLUSIONS: Anastomotic leakage adversely influenced local recurrence rates in stage II and III disease and was an independent risk factor for local recurrence. Additionally, anastomotic leakage contributed to failure to receive adjuvant chemotherapy in patients with stage III disease. PMID- 26283296 TI - Increased incidence of migraine in women correlates with obstetrics and gynaecological surgical procedures. AB - Migraine is a common chronic neurological disorder; yet no possible aetiology has been identified so far. There is a debate that migraine worsens in women who undergo procedures such as hysterectomy, dilation and curettage (D&C) or cesarean section for delivery. Hence, the present study was attempted to explore the link between procedures like D&C, hysterectomy and cesarean section for delivery and the prevalence of migraine in women. A total of 185 migraine patients were screened based on the inclusion and exclusion criteria of the International Headache Classification guidelines and 70 females who satisfied the inclusion criteria were included for the study. Of the 70 female patients, the numbers of married and unmarried women were 47 and 27, respectively. About 36 married women (80%, 95% CI: 0.146-0.104) had undergone the procedures related to obstetrics and gynaecology as per their medical history. Interestingly, 12 patients (33%, 95% CI: 0.148-0.176) had not experienced migraine attack prior to the above mentioned surgeries. Although, the age adjusted incidence of diagnosed migraine per 100,000 populations showed higher risk between 16-20 years of age (95% CI: 0.104-0.121), significant risk (95% CI: 0.086-0.113) was also observed in the women of 31-35 years age group in the present study. Based on the present study, surgeries such as D&C, hysterectomy and cesarean section for delivery increased the prevalence of migraine in women. Therefore, such procedures should be avoided unless otherwise essential, particularly in patients with positive past history of migraine. PMID- 26283297 TI - Inhibition of reactive oxygen species downregulates the MAPK pathway in rat spinal cord after limb ischemia reperfusion injury. AB - INTRODUCTION: We examined the activity of mitogen-activated protein kinase (MAPK) family members, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, in rats pinal cord after hind limb ischemia reperfusion (IR) and analyzed the role of reactive oxygen species (ROS) as mediators of MAPK signaling under these conditions. METHODS: In experiment 1, hind limb IR rats were treated intraperitoneally with one of following agents at 30 min before reperfusion: allopurinol (4, 40 mg/kg), superoxide dismutase (SOD, 4000 U/kg), N nitro-l-arginine methyl ester (l-NAME, 10 mg/kg), or SOD (4000 U/kg) + l-NAME (10 mg/kg). In experiment 2, 5,10,15,20-tetrakis (N-methyl-4'-pyridyl) porphyrinato iron (III) (FeTMPyP) was administered intraperitoneally (1, 3, or 10 mg/kg) 30 min before reperfusion. After 3 d reperfusion period, the spinal cord (L4-6) was harvested to investigate MAPK signaling activity. RESULTS: In experiment 1, p-ERK and p-JNK levels were significantly higher in the IR group than sham group. Administration of allopurinol, SOD, l-NAME, or SOD + l-NAME significantly reduced the IR-induced increase in p-ERK and p-JNK levels. There were no significant differences in p-p38 levels. In experiment 2, FeTMPyP significantly reduced the IR-induced increase in p-ERK and p-JNK levels in a dose-dependent manner. CONCLUSIONS: Activation of ERK and JNK in the spinal cord was induced by hind limb IR and was not accompanied by p38 activation. IR-induced MAPK phosphorylation was reduced by inhibition of superoxide, nitric oxide, and peroxynitrite, indicating that ROS produced by hind limb IR mediate the activation of these signaling pathways in the spinal cord, potentially affecting distant organs. PMID- 26283298 TI - Patterned hypopigmentation associated with prenatally diagnosed trisomy 7 mosaicism: long-term follow-up. PMID- 26283299 TI - Imaging breast cancer morphology using probe-based confocal laser endomicroscopy: towards a real-time intraoperative imaging tool for cavity scanning. AB - Current techniques for assessing the adequacy of tumour excision during breast conserving surgery do not provide real-time direct cytopathological assessment of the internal cavity walls within the breast. This study investigates the ability of probe-based confocal laser endomicroscopy (pCLE), an emerging imaging tool, to image the morphology of neoplastic and non-neoplastic breast tissues, and determines the ability of histopathologists and surgeons to differentiate these images. Freshly excised tumour samples and adjacent non-diseased sections from 50 consenting patients were stained with 0.01 % acriflavine hydrochloride and imaged using pCLE. All discernible pCLE features were cross-examined with conventional histopathology. Following pattern recognition training, 17 histopathologists and surgeons with no pCLE experience interpreted 50 pCLE images independently whilst blinded to histopathology results. Three-hundred and fifty pCLE image mosaics were analysed. Consistent with histopathology findings, the glandular structures, adipocytes and collagen fibres of normal breast were readily visible on pCLE images. These were distinguishable from the morphological architecture exhibited by invasive and non-invasive carcinoma. The mean accuracy of pCLE image interpretation for histopathologists and surgeons was 94 and 92 %, respectively. Overall, inter-observer agreement for histopathologists was 'almost perfect', kappa = 0.82; and 'substantial' for surgeons, kappa = 0.74. pCLE morphological features of neoplastic and non-neoplastic breast tissues are readily visualized and distinguishable with high accuracy by both histopathologists and surgeons. Further research is required to investigate a potential role for the use of pCLE intraoperatively for in situ detection of residual cancerous foci, thereby guiding operating decision-making based on real-time breast cavity scanning. PMID- 26283300 TI - Meta-analysis to determine the clinical impact of axillary lymph node dissection in the treatment of invasive breast cancer. AB - There are divergent opinions regarding the optimum surgical management of the axilla in patients with invasive breast cancer. Guidelines mandate axillary lymph node dissection (ALND) in the setting of positive sentinel lymph nodes. However, recent studies have questioned the true benefits of this procedure. Therefore, a meta-analysis of relevant randomized trials was performed in order to clarify the oncological benefit of axillary lymph node dissection. A comprehensive search of published randomized trials that compared patients with primary operable breast cancer with/without ALND was performed using MEDLINE, and available data were cross-referenced. Reviews of each study were conducted, and data were extracted. Primary outcomes were overall survival and recurrent axillary disease. A total of 7347 patients with operable primary breast cancer were identified from 8 randomised controlled trials comparing axillary recurrence in patients with or without ALND. Six of these trials provided data on overall survival on 6895 patients. Overall survival favours patients having ALND (OR = 1.22 (95% CI 1.03 1.44, p = 0.02). Similarly, patients undergoing ALND had increased recurrence free survival (OR = 2.25 (95% CI 1.28-3.94, p = 0.0047). ALND appears to positively impact on overall and recurrence-free survival from breast cancer. These data highlight the enduring benefits of ALND in an era where adjuvant therapies are being promoted to manage regionally advanced/metastatic disease. PMID- 26283302 TI - Diabetic foot disease: When the alarm to action is missing. PMID- 26283301 TI - Developing in vitro models of human ductal carcinoma in situ from primary tissue explants. AB - Because there are currently no reliable predictors for progression of ductal carcinoma in situ (DCIS) to invasive disease, nearly all patients receive comprehensive therapy, leading to over-treatment in many cases. Few in vitro models for studying DCIS progression have been developed. We report here the successful culture and expansion of primary DCIS from surgical specimens using a conditional reprogramming protocol. Patients with percutaneous core-needle biopsy demonstrating DCIS were enrolled in a tissue banking protocol after informed consent was received. Fresh tissue was taken from lumpectomy or mastectomy specimens, mechanically and enzymatically dissociated, cultured in medium conditioned by irradiated mouse fibroblasts and supplemented with rho-associated protein kinase (ROCK) inhibitor, and characterized by immunocytochemistry. Out of 33 DCIS cases, 58% (19) were expanded for up to 2 months in culture, and 42% (14) were frozen immediately after mechanical dissociation for future growth. The cultures are almost exclusively composed of cytokeratin 8- and EpCAM-positive luminal and cytokeratin 14-, cytokeratin 5-, and p63-positive basal mammary epithelial cells, suggesting maintenance of heterogeneity in vitro. Furthermore, as assessed by luminal and basal marker expression, these cells retain their cellular identities both in the "conditionally reprogrammed" proliferative state and after conditioned media and ROCK inhibitor withdrawal. When grown to 100 % confluency, the cultures organize into luminal and basal layers as well as luminal compartments surrounded by basal cells. Primary cultures of DCIS derived directly from patient tissues can be generated and may serve as in vitro models for the study of DCIS. PMID- 26283303 TI - Postoperative exercise training is associated with reduced respiratory infection rates and early discharge: A case-control study. AB - INTRODUCTION: Pulmonary complications are a significant cause of morbidity, mortality and increased hospital stay following complex abdominal surgery. We investigated whether postoperative early aerobic activity with a pedal exerciser reduced respiratory morbidity and length of stay and improved pulmonary function. METHODS: A prospective case-control study on 30 cases and 30 case matched controls aged 18 years or more who underwent major surgery was conducted. Controls were case-mix matched prospectively from a similar general surgical service not utilising postoperative exercising. Thirty consecutive cases were started on a twice-daily aerobic exercise program with pedal exerciser post operatively day 2 or from when sitting independently. Primary outcome measures were respiratory tract infection (RTI), deep vein thrombosis (DVT) or pulmonary embolus (PE). Secondary outcome measure was subjective breathlessness and Length of Stay (LOS) postoperatively. RESULTS: The rate of RTI was only 16.6% in the exercise group and 43.3% in the control group (P = 0.024). None of the cases or controls suffered from a DVT or PE. Median postoperative length of stay in the control group was 11 +/- 7.5 days whereas in the cases it was 8.5 +/- 5.00 days (P = 0.049). The Borg subjective breathlessness score in the cases group showed a decline in the subjective breathlessness on postoperative day 4 (P = 0.002). CONCLUSIONS: Early aerobic activity with a pedal exerciser halves the rate of postoperative RTI and postoperative hospital stay after complex abdominal surgery. Subjective breathlessness was also reduced with the use of pedal exerciser, signifying potential to improve exercise endurance in the postoperative patient. PMID- 26283304 TI - Thoughts, emotions, and dissociative features differentiate patients with epilepsy from patients with psychogenic nonepileptic spells (PNESs). AB - Psychogenic nonepileptic spells (PNESs) are often very difficult to treat, which may be, in part, related to the limited information known about what a person experiences while having PNESs. For this retrospective study, thoughts, emotions, and dissociative features during a spell were evaluated in 351 patients diagnosed with PNESs (N=223) or epilepsy (N=128). We found that a statistically higher number of thoughts, emotions, and dissociative symptoms were endorsed by patients with PNESs versus patients with epilepsy. Patients with PNESs reported significantly more anxiety and frustration, but not depression, compared with those with epilepsy. Emotions and dissociations, but not thoughts, and a history of any type of abuse were endorsed significantly more often by patients with PNESs. Patients with PNESs are prone to having poor outcomes, and interventions focusing on their actual experiences may be helpful for treatment planning. PMID- 26283305 TI - Juvenile myoclonic epilepsy and narcolepsy: A series of three cases. AB - OBJECTIVE: This paper sets out to demonstrate the coexistence of juvenile myoclonic epilepsy (JME) and narcolepsy that raises the possibility of a shared genetic predisposition to both conditions. METHODS: The electronic medical records (EMRs) were searched for narcolepsy and JME over 10years. RESULTS: We identified three young adult women diagnosed with JME in their teenage years, with myoclonic, generalized tonic-clonic, and absence seizure semiologies, along with psychiatric comorbidity, well managed on lamotrigine and/or levetiracetam. Our patients were also found to have disturbed sleep preceding the diagnosis of JME by many years, including excessive daytime sleepiness (EDS), fragmented nocturnal sleep, hypnagogic vivid hallucinations, and REM behavior disorder along with daytime cataplexy. They were ultimately diagnosed with coexisting narcolepsy, confirmed by sleep studies and multiple sleep latency testing, along with positive genetic testing for HLA-DQB1*0602 in all three patients. Stimulants, selective serotonin receptor inhibitors, and/or sodium oxybate were used to successfully treat their narcolepsy. SIGNIFICANCE: The coexistence of JME and narcolepsy has not been well recognized and may be clinically relevant. In addition, it raises the possibility of a shared genetic predisposition to both conditions. PMID- 26283306 TI - Congenital malformations in infants exposed to antiepileptic medications in utero at Boston Medical Center from 2003 to 2010. AB - OBJECTIVE: The aim of this study was to determine the frequency of association of major congenital malformations in pregnancy in women exposed to antiepileptic drugs (AEDs) in an inner city population. BACKGROUND: Approximately 0.3-0.5% of all pregnancies involve women with epilepsy. The risk of congenital malformations associated with AED therapy has been well documented, ranging from 2 to 10% as compared to a rate of 3% in the general population. However, the risk of these occurring in a higher risk population, such as an inner city tertiary care center, with multiple comorbidities is not as well known. DESIGN/METHODS: Using the Boston Medical Center Database between the years 2003 and 2010, a list of all infants born with major congenital malformations (MCMs) to mothers on AEDs was compiled. Major congenital malformations were defined as cleft lip and/or palate, ventricular or atrial septal defect, other cardiac malformations, and urogenital defects. During pregnancy, AED exposure including serum levels, other medication exposures, breakthrough seizure frequency, positive toxicology tests, and other maternal comorbidities were also analyzed. RESULTS: Of 17,246 live births between 2003 and 2010, 330 of those births demonstrated a MCM (malformation rate of 1.91%). Of those births, 64 mothers had epilepsy and were exposed to AED therapy during pregnancy, accounting for 0.37% of all births during this time period. Overall, three pregnancies in women with epilepsy resulted in a baby with a MCM, accounting for a 4.7% malformation rate in this patient population. In mothers on AEDs for other indications, the MCM rate was slightly higher, 5.0%, and in women on benzodiazepine monotherapy during pregnancy, the rate was quite high, 10.6%. PMID- 26283307 TI - Stenting Versus Aggressive Medical Management for Symptomatic Vertebral Artery Stenosis. PMID- 26283308 TI - Laser-wakefield accelerators as hard x-ray sources for 3D medical imaging of human bone. AB - A bright MUm-sized source of hard synchrotron x-rays (critical energy Ecrit > 30 keV) based on the betatron oscillations of laser wakefield accelerated electrons has been developed. The potential of this source for medical imaging was demonstrated by performing micro-computed tomography of a human femoral trabecular bone sample, allowing full 3D reconstruction to a resolution below 50 MUm. The use of a 1 cm long wakefield accelerator means that the length of the beamline (excluding the laser) is dominated by the x-ray imaging distances rather than the electron acceleration distances. The source possesses high peak brightness, which allows each image to be recorded with a single exposure and reduces the time required for a full tomographic scan. These properties make this an interesting laboratory source for many tomographic imaging applications. PMID- 26283310 TI - SIMAT: GC-SIM-MS data analysis tool. AB - BACKGROUND: Gas chromatography coupled with mass spectrometry (GC-MS) is one of the technologies widely used for qualitative and quantitative analysis of small molecules. In particular, GC coupled to single quadrupole MS can be utilized for targeted analysis by selected ion monitoring (SIM). However, to our knowledge, there are no software tools specifically designed for analysis of GC-SIM-MS data. In this paper, we introduce a new R/Bioconductor package called SIMAT for quantitative analysis of the levels of targeted analytes. SIMAT provides guidance in choosing fragments for a list of targets. This is accomplished through an optimization algorithm that has the capability to select the most appropriate fragments from overlapping chromatographic peaks based on a pre-specified library of background analytes. The tool also allows visualization of the total ion chromatograms (TIC) of runs and extracted ion chromatograms (EIC) of analytes of interest. Moreover, retention index (RI) calibration can be performed and raw GC SIM-MS data can be imported in netCDF or NIST mass spectral library (MSL) formats. RESULTS: We evaluated the performance of SIMAT using two GC-SIM-MS datasets obtained by targeted analysis of: (1) plasma samples from 86 patients in a targeted metabolomic experiment; and (2) mixtures of internal standards spiked in plasma samples at varying concentrations in a method development study. Our results demonstrate that SIMAT offers alternative solutions to AMDIS and MetaboliteDetector to achieve accurate detection of targets and estimation of their relative intensities by analysis of GC-SIM-MS data. CONCLUSIONS: We introduce a new R package called SIMAT that allows the selection of the optimal set of fragments and retention time windows for target analytes in GC-SIM-MS based analysis. Also, various functions and algorithms are implemented in the tool to: (1) read and import raw data and spectral libraries; (2) perform GC-SIM MS data preprocessing; and (3) plot and visualize EICs and TICs. PMID- 26283311 TI - E-waste management and resources recovery in France. AB - There are various issues of concern regarding electronic waste management, such as the toxicity of hazardous materials and the collection, recycling and recovery of useful resources. To understand the fate of electronic waste after collection and recycling, a products and materials flow analysis should be performed. This is a critical need, as material resources are becoming increasingly scarce and recycling may be able to provide secondary sources for new materials in the future. In this study, we investigate electronic waste systems, specifically the resource recovery or recycling aspects, as well as mapping electronic waste flows based on collection data in France. Approximately 1,588,453 t of new electrical and electronic equipment were sold in the French market in 2010. Of this amount, 430,000 t of electronic waste were collected, with the remaining 1,128,444 t remaining in stock. Furthermore, the total recycled amounts were 354,106 t and 11,396 t, respectively. The main electronic waste materials were ferrous metals (37%), plastic (22%), aluminium (12%), copper (11%) and glass (7%). This study will contribute to developing sustainable electronic waste and resource recycling systems in France. PMID- 26283309 TI - Transient CNS responses to repeated binge ethanol treatment. AB - The effects of ethanol (EtOH) on in vivo magnetic resonance (MR)-detectable brain measures across repeated exposures have not previously been reported. Of 28 rats weighing 340.66 +/- 21.93 g at baseline, 15 were assigned to an EtOH group and 13 to a control group. Animals were exposed to five cycles of 4 days of intragastric (EtOH or dextrose) treatment and 10 days of recovery. Rats in both groups had structural MR imaging and whole-brain MR spectroscopy (MRS) scans at baseline, immediately following each binge period and after each recovery period (total = 11 scans per rat). Blood alcohol level at each of the five binge periods was ~300 mg/dl. Blood drawn at the end of the experiment did not show group differences for thiamine or its phosphate derivatives. Postmortem liver histopathology provided no evidence for hepatic steatosis, alcoholic hepatitis or alcoholic cirrhosis. Cerebrospinal fluid volumes of the lateral ventricles and cisterns showed enlargement with each binge EtOH exposure but recovery with each abstinence period. Similarly, changes in MRS metabolite levels were transient: levels of N-acetylaspartate and total creatine decreased, while those of choline containing compounds and the combined resonance from glutamate and glutamine increased with each binge EtOH exposure cycle and then recovered during each abstinence period. Changes in response to EtOH were in expected directions based on previous single-binge EtOH exposure experiments, but the current MR findings do not provide support for accruing changes with repeated binge EtOH exposure. PMID- 26283312 TI - Effect of neodymium:yttrium-aluminum-garnet laser and fluoride on the acid demineralization of enamel. AB - AIM: The aim of the present study was to evaluate the protective effect of the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser and acidic phosphate fluoride (APF) on enamel erosion caused by hydrochloric acid. METHODS: Fifty human enamel specimens were distributed according to the following treatments (n = 10): untreated (control), APF (1.23%) 4 min, Nd:YAG laser (100 mJ, 1 W, 10 Hz, 141.5 J/cm2 ), APF + Nd:YAG laser, and Nd:YAG laser + APF. For 14 days the specimens were submitted to erosive challenge: 5 min in 3 mL hydrochloric acid (0.01 M, pH 2.2), rinsed with distilled water, and stored in artificial saliva for 3 h. This cycle was repeated four times per day. The calcium (Ca) loss was determined in demineralizing solution by atomic emission spectroscopy, and superficial roughness (Ra) was measured before and after the erosive challenge. RESULTS: The mean Ca loss was (mg/L, +/- standard deviation): control 12.74 +/- 3.33, APF 1.71 +/- 0.11, laser 1.64 +/- 0.08, APF + laser 1.38 +/- 0.08, and laser + APF 1.48 +/ 0.07. Kruskal-Wallis test showed a significant difference between the control and other groups. APF + laser showed minor loss of Ca. After the erosive challenge, the APF + laser group showed Ra alteration. CONCLUSION: A significant reduction in tooth dissolution was observed after fluoride application combined with Nd:YAG irradiation. PMID- 26283313 TI - Comparison of different process strategies for bioethanol production from Eucheuma cottonii: An economic study. AB - The aim of this work was to evaluate the efficacy of red macroalgae Eucheuma cottonii (EC) as feedstock for third-generation bioethanol production. Dowex (TM) Dr-G8 was explored as a potential solid catalyst to hydrolyzed carbohydrates from EC or macroalgae extract (ME) and pretreatment of macroalgae cellulosic residue (MCR), to fermentable sugars prior to fermentation process. The highest total sugars were produced at 98.7 g/L when 16% of the ME was treated under the optimum conditions of solid acid hydrolysis (8% (w/v) Dowex (TM) Dr-G8, 120 degrees C, 1h) and 2% pretreated MCR (P-MCR) treated by enzymatic hydrolysis (pH 4.8, 50 degrees C, 30 h). A two-stream process resulted in 11.6g/L of bioethanol from the fermentation of ME hydrolysates and 11.7 g/L from prehydrolysis and simultaneous saccharification and fermentation of P-MCR. The fixed price of bioethanol obtained from the EC is competitive with that obtained from other feedstocks. PMID- 26283314 TI - Retraction Note to: The role of TGFbeta1 stimulating ROCK I signal pathway to reorganize actin in a rat experimental model of developmental dysplasia of the hip. PMID- 26283315 TI - Retraction Note to: Identification of genes associated with the differentiation potential of adipose-derived stem cells to osteocytes or myocytes. PMID- 26283316 TI - Fitness responses to co-infestation in fleas exploiting rodent hosts. AB - To understand mechanisms behind positive interspecific co-occurrences in flea infracommunities, we asked whether co-infestation results in an increase of flea fitness (quantity and/or quality of the offspring). We studied reproductive performance of Xenopsylla ramesis and Parapulex chephrenis when they exploited their characteristic host (Meriones crassus and Acomys cahirinus, respectively) either alone or together with another species. We used egg production, the number of new imagoes, pre-imaginal survival and egg size as fitness-related variables and predicted that fitness will be higher in fleas feeding in mixed- than in single-species groups. In both fleas, mean number of eggs produced per female flea did not depend on experimental treatment. No effect of single- vs mixed species infestation on the mean number of new imagoes per female and the number of emerged imagoes per egg was found for X. ramesis, whereas both these numbers were higher in mixed- than in single-species groups for P. chephrenis. X. ramesis produced eggs of similar size independently of treatment, whereas eggs produced by P. chephrenis in mixed-species groups were significantly larger than eggs produced in single-species groups. We conclude that an increase in reproductive performance as a response to co-infestation may be one of the mechanisms behind aggregative structure of flea infracommunities. However, this response may vary among flea species. PMID- 26283318 TI - Abstracts 7th international congress "sepsis and multiorgan dysfunction". PMID- 26283319 TI - Growth responses of indigenous Frankia populations to edaphic factors in actinorhizal rhizospheres. AB - Quantitative PCR (qPCR) was used to follow population dynamics of indigenous Frankia populations in bulk soil, in leaf-litter-amended soil and in the rhizosphere of Alnus glutinosa or Casuarina equisetifolia at 2 matric potentials representing dry and wet conditions in soil microcosms. Analyses revealed between 10- and 100-fold increases of Frankia populations within the incubation period of 12 weeks independent of treatment. Numbers were generally higher under dry conditions and in the rhizosphere, with that of C. equisetifolia supporting highest abundance. Frankiae detected at any time and treatment belonged to either subgroup I of the Alnus host infection group or the Elaeagnus host infection group, with those of the Elaeagnus host infection group largely representing the genus in all samples under wet conditions, and in bulk and leaf litter amended soil under dry conditions. Subgroup I of the Alnus host infection group was most prominent in the rhizosphere of both plant species where it represented up to 95% of the genus with higher percentages in that of C. equisetifolia. PMID- 26283322 TI - [2D strain in dilated cardiomyopathy]. PMID- 26283321 TI - Effects of pyrite bioleaching solution of Acidithiobacillus ferrooxidans on viability, differentiation and mineralization potentials of rat osteoblasts. AB - Iron pyrite, an important component of traditional Chinese medicine, has a poor solubility, bioavailability, and patient compliance due to a high dose required and associated side effects, all of which have limited its clinical applications and experimental studies on its action mechanisms in improving fracture healing. This study investigated Acidithiobacillus ferrooxidans (A.f)-bioleaching of two kinds of pyrites and examined bioactivities of the derived solutions in viability and osteogenic differentiation in rat calvarial osteoblasts. A.f bioleaching improved element contents (Fe, Mn, Zn, Cu, and Se) in the derived solutions and the solutions concentration-dependently affected osteoblast viability and differentiation. While the solutions had no effects at low concentrations and inhibited the osteoblast alkaline phosphatase (ALP) activity at high concentrations, they improved ALP activity at their optimal concentrations. The improved osteoblast differentiation and osteogenic function at optimal concentrations were also revealed by levels of ALP cytochemical staining, calcium deposition, numbers and areas of mineralized nodules formed, mRNA and protein expression levels of osteogenesis-related genes (osteocalcin, Bmp-2, Runx-2, and IGF-1), and Runx-2 nuclear translocation. Data from this study will be useful in offering new strategies for improving pyrite bioavailability and providing a mechanistic explanation for the beneficial effects of pyrite in improving bone healing. PMID- 26283323 TI - [The development of Spanish paediatric cardiology and its impact on congenital heart disease management]. PMID- 26283325 TI - Associations of fish oil and vitamin B and E supplementation with cardiovascular outcomes and mortality in people receiving haemodialysis: a review. AB - BACKGROUND: Cardiovascular complications are the leading cause of mortality in patients with end-stage kidney disease. Research indicates that the Mediterranean diet is protective of cardiovascular disease in the general population. Components of this diet have been trialled in haemodialysis patients with the aim of reducing the risk of cardiovascular disease and improving associated risk factors. Components include fish, fruit and vegetables in the form of fish oil supplements and vitamin and antioxidant supplements. This narrative review provides an overview of observational studies, and interventional and randomised controlled trials examining the association of these supplements with cardiovascular outcomes in haemodialysis patients. METHODS: We reviewed the relevant literature by searching English-language publications in Web of Science and references from relevant articles published since 1992. Eight-seven abstracts were reviewed and 38 relevant articles were included. RESULTS: The extant literature suggests that risk of mortality is reduced in patients with a higher fish intake and those with higher serum omega-3 fatty acid levels. However, the pathways by which risk of mortality is reduced have not been fully extrapolated. While only a few studies have examined the effect of vitamin B supplementation in haemodialysis patients, these studies suggest that supplementation alone does not reduce the risk of mortality. Finally, studies examining vitamin E supplementation have drawn inconsistent conclusions regarding its pro-oxidant or antioxidant effects. Differences between studies are likely due to methodological variations in regards to dose, route of administration and treatment duration. CONCLUSIONS: Nutritional and dietary supplementation in haemodialysis patients is an area which requires larger, more methodologically robust randomised controlled trials to determine if risk of cardiovascular outcomes can be improved. PMID- 26283324 TI - Mechanisms of angiogenesis in a Curculigoside A-treated rat model of cerebral ischemia and reperfusion injury. AB - Curculigoside A has shown protective effects against rat cortical neuron damage in vivo. However, the molecular mechanisms through which Curculigoside A affords this protection are unclear. In the present study, we sought to elucidate the mechanisms of angiogenesis in rat aortic endothelial cells (RAEC), rat aortic smooth muscle cells (RASMC) as well as a rat model of cerebral ischemia and reperfusion injury following treatment with Curculigoside A. We examined the role of Curculigoside A on RAEC and RASMC proliferation, migration, and tube formation in vitro and in a cerebral ischemia and reperfusion injury rat model. We used the recombinant Dickkopf (DKK)-1 protein, a Wnt/beta-catenin inhibitor, and the recombinant WIF-1 protein, a Wnt5a antagonist to determine mechanisms. In addition, we measured leakage of the blood-brain barrier (BBB) and tested for angiogenesis associated proteins. Our data suggest that Curculigoside A induces angiogenesis in vitro by increasing proliferation, migration and tube formation in RAEC and RASMC. The increase in Curculigoside A-induced proliferation and tube formation was counteracted by DKK-1 and WIF-1. Curculigoside A increased expression of VEGF, p-VEGFR, p-CREB, Egr-3, VCAM-1, Ang1 and Tie2 while prohibiting BBB leakage in cerebral ischemia and reperfusion injured rats. However, Cyclosporine A, a CREB inhibitor, reduced the expression of p-CREB, Egr 3, VCAM-1, Ang1 and Tie2. These data suggest that Curculigoside A induces cell proliferation and angiogenesis through the Wnt5a/beta-catenin and VEGF/CREB/Egr 3/VCAM-1 signaling axis and promotes maturation and stability of new blood vessels via increasing Ang1 and Tie-2 expression. PMID- 26283326 TI - Are photographs a suitable alternative to dental study casts when assessing primary surgical outcome in children born with unilateral cleft lip and palate? AB - OBJECTIVE: To compare the use of the 5-year-olds' index on both dental study casts and intraoral photographs when measuring primary surgical outcome for children born with unilateral cleft lip and palate (UCLP). DESIGN: A cross sectional study. SETTING: Models and photographs collected from cleft units across the UK as part of the CCUK (Cleft Care UK) study were scored by two clinicians at the School of Oral and Dental Sciences, Bristol, UK. PARTICIPANTS: Five-year-old children born with UCLP as part of the CCUK study. One hundred and ninety-eight had dental study casts available and 49 had intraoral photographs available. METHODS: The records of both groups, that is study casts (n = 198) and photographs (n = 49) were scored using the 5-year-olds' index on two occasions by two examiners. RESULTS: Reliability of scoring is reduced for intraoral photographs compared with dental study casts. Using weighted Kappa the inter rater reliability for dental study casts was 0.72 to 0.77 and the inter-rater reliability for intraoral photographs was 0.52 to 0.59. LIMITATIONS: The photographs and study casts were not matched for each individual and were collected by a number of different clinicians in each unit, both of which will have had an effect on the quality and consistency of the final records. CONCLUSIONS: Dental study casts provide more reliable results and thus still represent the gold standard when assessing primary surgical outcome in cleft care using the 5-year-olds' index. PMID- 26283327 TI - Biomarkers in community-acquired pneumonia. PMID- 26283320 TI - Classifying the bacterial gut microbiota of termites and cockroaches: A curated phylogenetic reference database (DictDb). AB - Recent developments in sequencing technology have given rise to a large number of studies that assess bacterial diversity and community structure in termite and cockroach guts based on large amplicon libraries of 16S rRNA genes. Although these studies have revealed important ecological and evolutionary patterns in the gut microbiota, classification of the short sequence reads is limited by the taxonomic depth and resolution of the reference databases used in the respective studies. Here, we present a curated reference database for accurate taxonomic analysis of the bacterial gut microbiota of dictyopteran insects. The Dictyopteran gut microbiota reference Database (DictDb) is based on the Silva database but was significantly expanded by the addition of clones from 11 mostly unexplored termite and cockroach groups, which increased the inventory of bacterial sequences from dictyopteran guts by 26%. The taxonomic depth and resolution of DictDb was significantly improved by a general revision of the taxonomic guide tree for all important lineages, including a detailed phylogenetic analysis of the Treponema and Alistipes complexes, the Fibrobacteres, and the TG3 phylum. The performance of this first documented version of DictDb (v. 3.0) using the revised taxonomic guide tree in the classification of short-read libraries obtained from termites and cockroaches was highly superior to that of the current Silva and RDP databases. DictDb uses an informative nomenclature that is consistent with the literature also for clades of uncultured bacteria and provides an invaluable tool for anyone exploring the gut community structure of termites and cockroaches. PMID- 26283328 TI - Administration of antibiotic agents before intraoperative sampling in orthopedic infections alters culture results. AB - Many physicians and surgeons think that prescribing antibiotics before intraoperative sampling does not alter the microbiological results. METHODS: Case control study of adult patients hospitalized with orthopedic infections. RESULTS: Among 2740 episodes of orthopedic infections, 1167 (43%) had received antibiotic therapy before surgical sampling. Among these, 220 (19%) grew no pathogens while the proportion of culture-negative results in the 2573 who had no preoperative antibiotic therapy was only 6%. By multivariate analyses, pre-operative antibiotic exposure was associated with significantly more culture-negative results (odds ratio 2.8, 95% confidence interval 2.1-3.7), more non-fermenting rods and skin commensals (odds ratio 2.8 and 3.0, respectively). Even a single pre-operative dose of antibiotic was significantly associated with subsequent culture-negative results (19/93 vs. 297/2350; chi2-test, p = 0.01) and skin commensals (17/74 vs. 274/2350; p = 0.01) compared to episodes without preceding prophylaxis. CONCLUSIONS: Prior antibiotic use, including single-dose prophylactic administrations, is three-fold associated with culture-negative results, non-fermenting rods and resistant skin commensals. PMID- 26283329 TI - Chryseobacterium sediminis sp. nov., isolated from a river sediment. AB - A slightly yellow-pigmented strain (IMT-174T) isolated from a river sediment in Guyana was studied in detail for its taxonomic position. Cells of the isolate appeared rod-shaped and stained Gram-negative. Comparative 16S rRNA gene sequence analysis showed that the isolate had the highest sequence similarities to type strains of Chryseobacterium rhizoplanae (99.0 %), Chryseobacterium viscerum (98.9 %), Chryseobacterium lactis (98.8 %) and Chryseobacterium indologenes (98.6 %). The 16S rRNA gene sequence similarities to all other species of the genus Chryseobacterium were below 98.5 %. Fatty acid analysis of whole-cell hydrolysates of the strain resulted in a pattern typical of members of the genus Chryseobacterium, with fatty acids iso-C15 : 0, iso-C15 : 0 2-OH, iso-C17 : 1omega9c and iso-C17 : 0 3-OH as major compounds. The polyamine pattern contained predominantly sym-homospermidine. The major quinone was menaquinone MK-6 and the only lipid identified in the polar lipid profile was phosphatidylethanolamine. In addition, 13 unidentified lipids were detected in moderate to major amounts. DNA DNA hybridizations with type strains of C. rhizoplanae, C. viscerum, C. lactis and C. indologenes resulted in values below 70 %. In addition to the genotypic differences, differentiating biochemical and chemotaxonomic properties confirmed that isolate IMT-174T represents a novel species, for which the name Chryseobacterium sediminis sp. nov. (type strain IMT-174T = LMG 28695T = CIP 110895T) is proposed. PMID- 26283331 TI - A Single Amino Acid Replacement in the Sensor Kinase LiaS Contributes to a Carrier Phenotype in Group A Streptococcus. AB - Despite the high frequency of asymptomatic carriage of bacterial pathogens, we understand little about the bacterial molecular genetic underpinnings of this phenomenon. To obtain new information about the molecular genetic mechanisms underlying carriage of group A Streptococcus (GAS), we performed whole-genome sequencing of GAS strains recovered from a single individual during acute pharyngitis and subsequent asymptomatic carriage. We discovered that compared to the initial infection isolate, the strain recovered during asymptomatic carriage contained three single nucleotide polymorphisms, one of which was in a highly conserved region of a gene encoding a sensor kinase, liaS, resulting in an arginine-to-glycine amino acid replacement at position 135 of LiaS (LiaS(R135G)). Using gene replacement, we demonstrate that introduction of the carrier allele (liaS(R135G)) into a serotype-matched invasive strain increased mouse nasopharyngeal colonization and adherence to cultured human epithelial cells. The carrier mutation also resulted in a reduced ability to grow in human blood and reduced virulence in a mouse model of necrotizing fasciitis. Repair of the mutation in the GAS carrier strain restored virulence and decreased adherence to cultured human epithelial cells. We also provide evidence that the carrier mutation alters the GAS transcriptome, including altered transcription of GAS virulence genes, providing a potential mechanism for the pleiotropic phenotypic effects. Our data obtained using isogenic strains suggest that the liaS(R135G) mutation in the carrier strain contributes to the transition from disease to asymptomatic carriage and provides new information about this poorly described regulatory system in GAS. PMID- 26283330 TI - Plasmodium falciparum Gametocyte-Specific Antibody Profiling Reveals Boosting through Natural Infection and Identifies Potential Markers of Gametocyte Exposure. AB - Malaria elimination efforts would benefit from vaccines that block transmission of Plasmodium falciparum gametocytes from humans to mosquitoes. A clear understanding of gametocyte-specific antibody responses in exposed populations could help determine whether transmission-blocking vaccines (TBV) would be boosted by natural gametocyte exposure, and also inform the development of serologic tools to monitor gametocyte exposure in populations targeted for malaria elimination. To this end, plasma was collected from Malian children and adults before and after the 6-month malaria season and probed against a microarray containing 1,204 P. falciparum proteins. Using publicly available proteomic data, we classified 91 proteins as gametocyte specific and 69 as proteins not expressed by gametocytes. The overall breadth and magnitude of gametocyte-specific IgG responses increased during the malaria season, although they were consistently lower than IgG responses to nongametocyte antigens. Notably, IgG specific for the TBV candidates Pfs48/45 and Pfs230 increased during the malaria season. In addition, IgGs specific for the gametocyte proteins Pfmdv1, Pfs16, PF3D7_1346400, and PF3D7_1024800 were detected in nearly all subjects, suggesting that seroconversion to these proteins may be a sensitive indicator of gametocyte exposure, although further studies are needed to determine the specificity and kinetics of these potential serologic markers. These findings suggest that TBV-induced immunity would be boosted through natural gametocyte exposure, and that antibody responses to particular antigens may reliably indicate gametocyte exposure. PMID- 26283332 TI - Role of Inflammatory Monocytes in Vaccine-Induced Reduction of Helicobacter felis Infection. AB - Despite the proven ability of immunization to reduce Helicobacter infection in mouse models, the precise mechanism of protection has remained elusive. In this study, we evaluated the role of inflammatory monocytes in the vaccine-induced reduction of Helicobacter felis infection. We first showed by using flow cytometric analysis that Ly6C(low) major histocompatibility complex class II positive chemokine receptor type 2 (CCR2)-positive CD64(+) inflammatory monocytes accumulate in the stomach mucosa during the vaccine-induced reduction of H. felis infection. To determine whether inflammatory monocytes played a role in the protection, these cells were depleted with anti-CCR2 depleting antibodies. Indeed, depletion of inflammatory monocytes was associated with an impaired vaccine-induced reduction of H. felis infection on day 5 postinfection. To determine whether inflammatory monocytes had a direct or indirect role, we studied their antimicrobial activities. We observed that inflammatory monocytes produced tumor necrosis factor alpha and inducible nitric oxide synthase (iNOS), two major antimicrobial factors. Lastly, by using a Helicobacter in vitro killing assay, we showed that mouse inflammatory monocytes and activated human monocytes killed H. pylori in an iNOS-dependent manner. Collectively, these data show that inflammatory monocytes play a direct role in the immunization-induced reduction of H. felis infection from the gastric mucosa. PMID- 26283333 TI - Surface Glycopolymers Are Crucial for In Vitro Anti-Wall Teichoic Acid IgG Mediated Complement Activation and Opsonophagocytosis of Staphylococcus aureus. AB - The cell envelopes of many Gram-positive bacteria contain wall teichoic acids (WTAs). Staphylococcus aureus WTAs are composed of ribitol phosphate (RboP) or glycerol phosphate (GroP) backbones substituted with D-alanine and N-acetyl-D glucosamine (GlcNAc) or N-acetyl-D-galactosamine (GalNAc). Two WTA glycosyltransferases, TarM and TarS, are responsible for modifying the RboP WTA with alpha-GlcNAc and beta-GlcNAc, respectively. We recently reported that purified human serum anti-WTA IgG specifically recognizes beta-GlcNAc of the staphylococcal RboP WTA and then facilitates complement C3 deposition and opsonophagocytosis of S. aureus laboratory strains. This prompted us to examine whether anti-WTA IgG can induce C3 deposition on a diverse set of clinical S. aureus isolates. To this end, we compared anti-WTA IgG-mediated C3 deposition and opsonophagocytosis abilities using 13 different staphylococcal strains. Of note, the majority of S. aureus strains tested was recognized by anti-WTA IgG, resulting in C3 deposition and opsonophagocytosis. A minority of strains was not recognized by anti-WTA IgG, which correlated with either extensive capsule production or an alteration in the WTA glycosylation pattern. Our results demonstrate that the presence of WTAs with TarS-mediated glycosylation with beta GlcNAc in clinically isolated S. aureus strains is an important factor for induction of anti-WTA IgG-mediated C3 deposition and opsonophagocytosis. PMID- 26283334 TI - Gingipains from the Periodontal Pathogen Porphyromonas gingivalis Play a Significant Role in Regulation of Angiopoietin 1 and Angiopoietin 2 in Human Aortic Smooth Muscle Cells. AB - Angiopoietin 1 (Angpt1) and angiopoietin 2 (Angpt2) are the ligands of tyrosine kinase (Tie) receptors, and they play important roles in vessel formation and the development of inflammatory diseases, such as atherosclerosis. Porphyromonas gingivalis is a Gram-negative periodontal bacterium that is thought to contribute to the progression of cardiovascular disease. The aim of this study was to investigate the role of P. gingivalis infection in the modulation of Angpt1 and Angpt2 in human aortic smooth muscle cells (AoSMCs). We exposed AoSMCs to wild type (W50 and 381), gingipain mutant (E8 and K1A), and fimbrial mutant (DPG-3 and KRX-178) P. gingivalis strains and to different concentrations of tumor necrosis factor (TNF). The atherosclerosis risk factor TNF was used as a positive control in this study. We found that P. gingivalis (wild type, K1A, DPG3, and KRX178) and TNF upregulated the expression of Angpt2 and its transcription factor ETS1, respectively, in AoSMCs. In contrast, Angpt1 was inhibited by P. gingivalis and TNF. However, the RgpAB mutant E8 had no effect on the expression of Angpt1, Angpt2, or ETS1 in AoSMCs. The results also showed that ETS1 is critical for P. gingivalis induction of Angpt2. Exposure to Angpt2 protein enhanced the migration of AoSMCs but had no effect on proliferation. This study demonstrates that gingipains are crucial to the ability of P. gingivalis to markedly increase the expressed Angpt2/Angpt1 ratio in AoSMCs, which determines the regulatory role of angiopoietins in angiogenesis and their involvement in the development of atherosclerosis. These findings further support the association between periodontitis and cardiovascular disease. PMID- 26283335 TI - Viable but Nonculturable and Persister Cells Coexist Stochastically and Are Induced by Human Serum. AB - Dormancy holds a vital role in the ecological dynamics of microorganisms. Specifically, entry into dormancy allows cells to withstand times of stress while maintaining the potential for reentry into an active existence. The viable but nonculturable (VBNC) state and antibiotic persistence are two well-recognized conditions of dormancy demonstrated to contribute to bacterial stress tolerance and, as a consequence, yield populations that are tolerant to high-dose antibiotics. Aside from this commonality, more evidence is being presented that indicates the relatedness of these two states. Here, we demonstrate that VBNC cells are present during persister isolation experiments, further indicating that these cells coexist and are induced by the same conditions. Interestingly, we reveal that VBNC cells can exist stochastically in unstressed growing cultures, a finding that is characteristic of persisters. Furthermore, human serum induces the formation of both VBNC cells and persisters, a finding not previously described for either dormancy state. Lastly, we describe the role of toxin antitoxin systems (TAS) in the induction of the VBNC state and report that these TAS, which are classically implicated in persister cell formation, are also induced during incubation in human serum. This study provides evidence for the recently proposed "dormancy continuum hypothesis" and substantiates the physical and molecular relatedness of VBNC and persister cells in a standardized model organism. Notably, these results provide new evidence for the clinical significance of VBNC and persister cells. PMID- 26283337 TI - Campylobacter hyointestinalis Isolated from Pigs Produces Multiple Variants of Biologically Active Cytolethal Distending Toxin. AB - Campylobacter hyointestinalis isolated from swine with proliferative enteritis often is considered to be pathogenic. While the precise virulence mechanisms of this species remain unclear, we have recently identified a cytolethal distending toxin (cdt) gene cluster in C. hyointestinalis isolated from a patient with diarrhea (W. Samosornsuk et al., J Med Microbiol, 27 July 2015, http://dx.doi.org/10.1099/jmm.0.000145). However, the sequences of the cdt genes in C. hyointestinalis were found to be significantly different and the gene products are immunologically distinct from those of other Campylobacter species. In this study, we demonstrate the presence of a second variant of the cdt gene cluster in C. hyointestinalis, designated cdt-II, while the former is named cdt I. Sequencing of the cdt-II gene cluster and deduced amino acid sequences revealed that homologies between the subunits CdtA, CdtB, and CdtC of ChCDT-I and ChCDT-II are 25.0, 56.0, and 24.8%, respectively. Furthermore, the CdtB subunit of ChCDT-II was found to be immunologically unrelated to that of ChCDT-I by Ouchterlony double gel diffusion test. Recombinant ChCDT-II also induced cell distention and death of HeLa cells by blocking the cell cycle at G2/M phase. Interestingly, the cdt-II genes were detected in all 23 animal isolates and in 1 human isolate of C. hyointestinalis, and 21 of these strains carried both cdt-I and cdt-II gene clusters. Altogether, our results indicate that ChCDT-II is an important virulence factor of C. hyointestinalis in animals. PMID- 26283336 TI - MdsABC-Mediated Pathway for Pathogenicity in Salmonella enterica Serovar Typhimurium. AB - MdsABC is a Salmonella-specific tripartite efflux pump that has been implicated in the virulence of Salmonella enterica serovar Typhimurium; however, little is known about the virulence factors associated with this pump. We observed MdsABC expression-dependent alterations in the degree of resistance to extracellular oxidative stress and macrophage-mediated killing. Thin-layer chromatography and tandem mass spectrometry analyses revealed that overexpression of MdsABC led to increased secretion of 1-palmitoyl-2-stearoyl-phosphatidylserine (PSPS), affecting the ability of the bacteria to invade and survive in host cells. Overexpression of MdsABC and external addition of PSPS similarly rendered the mdsABC deletion strain resistant to diamide. Diagonal gel analysis showed that PSPS treatment reduced the diamide-mediated formation of disulfide bonds, particularly in the membrane fraction of the bacteria. Salmonella infection of macrophages induced the upregulation of MdsABC expression and led to an increase of intracellular bacterial number and host cell death, similar to the effects of MdsABC overexpression and PSPS pretreatment on the mdsABC deletion strain. Our study shows that MdsABC mediates a previously uncharacterized pathway that involves PSPS as a key factor for the survival and virulence of S. Typhimurium in phagocytic cells. PMID- 26283338 TI - The Mga Regulon but Not Deoxyribonuclease Sda1 of Invasive M1T1 Group A Streptococcus Contributes to In Vivo Selection of CovRS Mutations and Resistance to Innate Immune Killing Mechanisms. AB - Invasive M1T1 group A Streptococcus (GAS) can have a mutation in the regulatory system CovRS, and this mutation can render strains hypervirulent. Interestingly, via mechanisms that are not well understood, the host innate immune system's neutrophils select spontaneous M1T1 GAS CovRS hypervirulent mutants, thereby enhancing the pathogen's ability to evade immune killing. It has been reported that the DNase Sda1 is critical for the resistance of M1T1 strain 5448 to killing in human blood and provides pressure for in vivo selection of CovRS mutations. We reexamined the role of Sda1 in the selection of CovRS mutations and in GAS innate immune evasion. Deletion of sda1 or all DNase genes in M1T1 strain MGAS2221 did not alter emergence of CovRS mutants during murine infection. Deletion of sda1 in strain 5448 resulted in Deltasda1 mutants with (5448 Deltasda1(M+) strain) and without (5448 Deltasda1(M-) strain) M protein production. The 5448 Deltasda1(M+) strain accumulated CovRS mutations in vivo and resisted killing in the bloodstream, whereas the 5448 Deltasda1(M-) strain lost in vivo selection of CovRS mutations and was sensitive to killing. The deletion of emm and a spontaneous Mga mutation in MGAS2221 reduced and prevented in vivo selection for CovRS mutants, respectively. Thus, in contrast to previous reports, Sda1 is not critical for in vivo selection of invasive M1T1 CovRS mutants and GAS resistance to innate immune killing mechanisms. In contrast, M protein and other Mga regulated proteins contribute to the in vivo selection of M1T1 GAS CovRS mutants. These findings advance the understanding of the progression of invasive M1T1 GAS infections. PMID- 26283339 TI - Leptospira interrogans lpxD Homologue Is Required for Thermal Acclimatization and Virulence. AB - Leptospirosis is an emerging disease with an annual occurrence of over 1 million human cases worldwide. Pathogenic Leptospira bacteria are maintained in zoonotic cycles involving a diverse array of mammals, with the capacity to survive outside the host in aquatic environments. Survival in the diverse environments encountered by Leptospira likely requires various adaptive mechanisms. Little is known about Leptospira outer membrane modification systems, which may contribute to the capacity of these bacteria to successfully inhabit and colonize diverse environments and animal hosts. Leptospira bacteria carry two genes annotated as UDP-3-O-[3-hydroxymyristoyl] glucosamine N-acyltransferase genes (la0512 and la4326 [lpxD1 and lpxD2]) that in other bacteria are involved in the early steps of biosynthesis of lipid A, the membrane lipid anchor of lipopolysaccharide. Inactivation of only one of these genes, la0512/lpxD1, imparted sensitivity to the host physiological temperature (37 degrees C) and rendered the bacteria avirulent in an animal infection model. Polymyxin B sensitivity assays revealed compromised outer membrane integrity in the lpxD1 mutant at host physiological temperature, but structural analysis of lipid A in the mutant revealed only minor changes in the lipid A moiety compared to that found in the wild-type strain. In accordance with this, an in trans complementation restored the phenotypes to a level comparable to that of the wild-type strain. These results suggest that the gene annotated as lpxD1 in Leptospira interrogans plays an important role in temperature adaptation and virulence in the animal infection model. PMID- 26283340 TI - Simultaneous Host-Pathogen Transcriptome Analysis during Granulibacter bethesdensis Infection of Neutrophils from Healthy Subjects and Patients with Chronic Granulomatous Disease. AB - Polymorphonuclear leukocytes (PMN) from patients with chronic granulomatous disease (CGD) fail to produce microbicidal concentrations of reactive oxygen species (ROS) due to mutations in NOX2. Patients with CGD suffer from severe, life-threatening infections and inflammatory complications. Granulibacter bethesdensis is an emerging Gram-negative pathogen in CGD that resists killing by PMN of CGD patients (CGD PMN) and inhibits PMN apoptosis through unknown mechanisms. Microarray analysis was used to study mRNA expression in PMN from healthy subjects (normal PMN) and CGD PMN during incubation with G. bethesdensis and, simultaneously, in G. bethesdensis with normal and CGD PMN. We detected upregulation of antiapoptotic genes (e.g., XIAP and GADD45B) and downregulation of proapoptotic genes (e.g., CASP8 and APAF1) in infected PMN. Transcript and protein levels of inflammation- and immunity-related genes were also altered. Upon interaction with PMN, G. bethesdensis altered the expression of ROS resistance genes in the presence of normal but not CGD PMN. Levels of bacterial stress response genes, including the ClpB gene, increased during phagocytosis by both normal and CGD PMN demonstrating responses to oxygen-independent PMN antimicrobial systems. Antisense knockdown demonstrated that ClpB is dispensable for extracellular growth but is essential for bacterial resistance to both normal and CGD PMN. Metabolic adaptation of Granulibacter growth in PMN included the upregulation of pyruvate dehydrogenase. Pharmacological inhibition of pyruvate dehydrogenase by triphenylbismuthdichloride was lethal to Granulibacter. This study expands knowledge of microbial pathogenesis of Granulibacter in cells from permissive (CGD) and nonpermissive (normal) hosts and identifies potentially druggable microbial factors, such as pyruvate dehydrogenase and ClpB, to help combat this antibiotic-resistant pathogen. PMID- 26283341 TI - Conservation of the Host-Interacting Proteins Tp0750 and Pallilysin among Treponemes and Restriction of Proteolytic Capacity to Treponema pallidum. AB - The spirochete Treponema pallidum subsp. pallidum is the causative agent of syphilis, a chronic, sexually transmitted infection characterized by multiple symptomatic and asymptomatic stages. Although several other species in the genus are able to cause or contribute to disease, T. pallidum differs in that it is able to rapidly disseminate via the bloodstream to tissue sites distant from the site of initial infection. It is also the only Treponema species able to cross both the blood-brain and placental barriers. Previously, the T. pallidum proteins, Tp0750 and Tp0751 (also called pallilysin), were shown to degrade host proteins central to blood coagulation and basement membrane integrity, suggesting a role for these proteins in T. pallidum dissemination and tissue invasion. In the present study, we characterized Tp0750 and Tp0751 sequence variation in a diversity of pathogenic and nonpathogenic treponemes. We also determined the proteolytic potential of the orthologs from the less invasive species Treponema denticola and Treponema phagedenis. These analyses showed high levels of sequence similarity among Tp0750 orthologs from pathogenic species. For pallilysin, lower levels of sequence conservation were observed between this protein and orthologs from other treponemes, except for the ortholog from the highly invasive rabbit venereal syphilis-causing Treponema paraluiscuniculi. In vitro host component binding and degradation assays demonstrated that pallilysin and Tp0750 orthologs from the less invasive treponemes tested were not capable of binding or degrading host proteins. The results show that pallilysin and Tp0750 host protein binding and degradative capability is positively correlated with treponemal invasiveness. PMID- 26283342 TI - Symbiosis becoming permanent: Survival of the luckiest. PMID- 26283344 TI - An empirical model of the Baltic Sea reveals the importance of social dynamics for ecological regime shifts. AB - Regime shifts triggered by human activities and environmental changes have led to significant ecological and socioeconomic consequences in marine and terrestrial ecosystems worldwide. Ecological processes and feedbacks associated with regime shifts have received considerable attention, but human individual and collective behavior is rarely treated as an integrated component of such shifts. Here, we used generalized modeling to develop a coupled social-ecological model that integrated rich social and ecological data to investigate the role of social dynamics in the 1980s Baltic Sea cod boom and collapse. We showed that psychological, economic, and regulatory aspects of fisher decision making, in addition to ecological interactions, contributed both to the temporary persistence of the cod boom and to its subsequent collapse. These features of the social-ecological system also would have limited the effectiveness of stronger fishery regulations. Our results provide quantitative, empirical evidence that incorporating social dynamics into models of natural resources is critical for understanding how resources can be managed sustainably. We also show that generalized modeling, which is well-suited to collaborative model development and does not require detailed specification of causal relationships between system variables, can help tackle the complexities involved in creating and analyzing social-ecological models. PMID- 26283343 TI - Consistent responses of soil microbial communities to elevated nutrient inputs in grasslands across the globe. AB - Soil microorganisms are critical to ecosystem functioning and the maintenance of soil fertility. However, despite global increases in the inputs of nitrogen (N) and phosphorus (P) to ecosystems due to human activities, we lack a predictive understanding of how microbial communities respond to elevated nutrient inputs across environmental gradients. Here we used high-throughput sequencing of marker genes to elucidate the responses of soil fungal, archaeal, and bacterial communities using an N and P addition experiment replicated at 25 globally distributed grassland sites. We also sequenced metagenomes from a subset of the sites to determine how the functional attributes of bacterial communities change in response to elevated nutrients. Despite strong compositional differences across sites, microbial communities shifted in a consistent manner with N or P additions, and the magnitude of these shifts was related to the magnitude of plant community responses to nutrient inputs. Mycorrhizal fungi and methanogenic archaea decreased in relative abundance with nutrient additions, as did the relative abundances of oligotrophic bacterial taxa. The metagenomic data provided additional evidence for this shift in bacterial life history strategies because nutrient additions decreased the average genome sizes of the bacterial community members and elicited changes in the relative abundances of representative functional genes. Our results suggest that elevated N and P inputs lead to predictable shifts in the taxonomic and functional traits of soil microbial communities, including increases in the relative abundances of faster-growing, copiotrophic bacterial taxa, with these shifts likely to impact belowground ecosystems worldwide. PMID- 26283345 TI - Plasma metabolomic profiles enhance precision medicine for volunteers of normal health. AB - Precision medicine, taking account of human individuality in genes, environment, and lifestyle for early disease diagnosis and individualized therapy, has shown great promise to transform medical care. Nontargeted metabolomics, with the ability to detect broad classes of biochemicals, can provide a comprehensive functional phenotype integrating clinical phenotypes with genetic and nongenetic factors. To test the application of metabolomics in individual diagnosis, we conducted a metabolomics analysis on plasma samples collected from 80 volunteers of normal health with complete medical records and three-generation pedigrees. Using a broad-spectrum metabolomics platform consisting of liquid chromatography and GC coupled with MS, we profiled nearly 600 metabolites covering 72 biochemical pathways in all major branches of biosynthesis, catabolism, gut microbiome activities, and xenobiotics. Statistical analysis revealed a considerable range of variation and potential metabolic abnormalities across the individuals in this cohort. Examination of the convergence of metabolomics profiles with whole-exon sequences (WESs) provided an effective approach to assess and interpret clinical significance of genetic mutations, as shown in a number of cases, including fructose intolerance, xanthinuria, and carnitine deficiency. Metabolic abnormalities consistent with early indications of diabetes, liver dysfunction, and disruption of gut microbiome homeostasis were identified in several volunteers. Additionally, diverse metabolic responses to medications among the volunteers may assist to identify therapeutic effects and sensitivity to toxicity. The results of this study demonstrate that metabolomics could be an effective approach to complement next generation sequencing (NGS) for disease risk analysis, disease monitoring, and drug management in our goal toward precision care. PMID- 26283346 TI - A broadly neutralizing human monoclonal antibody is effective against H7N9. AB - Emerging strains of influenza represent a significant public health threat with potential pandemic consequences. Of particular concern are the recently emerged H7N9 strains which cause pneumonia with acute respiratory distress syndrome. Estimates are that nearly 80% of hospitalized patients with H7N9 have received intensive care unit support. VIS410, a human antibody, targets a unique conserved epitope on influenza A. We evaluated the efficacy of VIS410 for neutralization of group 2 influenza strains, including H3N2 and H7N9 strains in vitro and in vivo. VIS410, administered at 50 mg/kg, protected DBA mice infected with A/Anhui/2013 (H7N9), resulting in significant survival benefit upon single-dose (-24 h) or double-dose (-12 h, +48 h) administration (P < 0.001). A single dose of VIS410 at 50 mg/kg (-12 h) combined with oseltamivir at 50 mg/kg (-12 h, twice daily for 7 d) in C57BL/6 mice infected with A/Shanghai 2/2013 (H7N9) resulted in significant decreased lung viral load (P = 0.002) and decreased lung cytokine responses for nine of the 11 cytokines measured. Based on these results, we find that VIS410 may be effective either as monotherapy or combined with antivirals in treating H7N9 disease, as well as disease from other influenza strains. PMID- 26283347 TI - Montsechia, an ancient aquatic angiosperm. AB - The early diversification of angiosperms in diverse ecological niches is poorly understood. Some have proposed an origin in a darkened forest habitat and others an open aquatic or near aquatic habitat. The research presented here centers on Montsechia vidalii, first recovered from lithographic limestone deposits in the Pyrenees of Spain more than 100 y ago. This fossil material has been poorly understood and misinterpreted in the past. Now, based upon the study of more than 1,000 carefully prepared specimens, a detailed analysis of Montsechia is presented. The morphology and anatomy of the plant, including aspects of its reproduction, suggest that Montsechia is sister to Ceratophyllum (whenever cladistic analyses are made with or without a backbone). Montsechia was an aquatic angiosperm living and reproducing below the surface of the water, similar to Ceratophyllum. Montsechia is Barremian in age, raising questions about the very early divergence of the Ceratophyllum clade compared with its position as sister to eudicots in many cladistic analyses. Lower Cretaceous aquatic angiosperms, such as Archaefructus and Montsechia, open the possibility that aquatic plants were locally common at a very early stage of angiosperm evolution and that aquatic habitats may have played a major role in the diversification of some early angiosperm lineages. PMID- 26283348 TI - Endosymbionts escape dead hydrothermal vent tubeworms to enrich the free-living population. AB - Theory predicts that horizontal acquisition of symbionts by plants and animals must be coupled to release and limited dispersal of symbionts for intergenerational persistence of mutualisms. For deep-sea hydrothermal vent tubeworms (Vestimentifera, Siboglinidae), it has been demonstrated that a few symbiotic bacteria infect aposymbiotic host larvae and grow in a newly formed organ, the trophosome. However, whether viable symbionts can be released to augment environmental populations has been doubtful, because (i) the adult worms lack obvious openings and (ii) the vast majority of symbionts has been regarded as terminally differentiated. Here we show experimentally that symbionts rapidly escape their hosts upon death and recruit to surfaces where they proliferate. Estimating symbiont release from our experiments taken together with well-known tubeworm density ranges, we suggest a few million to 1.5 billion symbionts seeding the environment upon death of a tubeworm clump. In situ observations show that such clumps have rapid turnover, suggesting that release of large numbers of symbionts may ensure effective dispersal to new sites followed by active larval colonization. Moreover, release of symbionts might enable adaptations that evolve within host individuals to spread within host populations and possibly to new environments. PMID- 26283349 TI - Quantifying seasonal population fluxes driving rubella transmission dynamics using mobile phone data. AB - Changing patterns of human aggregation are thought to drive annual and multiannual outbreaks of infectious diseases, but the paucity of data about travel behavior and population flux over time has made this idea difficult to test quantitatively. Current measures of human mobility, especially in low-income settings, are often static, relying on approximate travel times, road networks, or cross-sectional surveys. Mobile phone data provide a unique source of information about human travel, but the power of these data to describe epidemiologically relevant changes in population density remains unclear. Here we quantify seasonal travel patterns using mobile phone data from nearly 15 million anonymous subscribers in Kenya. Using a rich data source of rubella incidence, we show that patterns of population travel (fluxes) inferred from mobile phone data are predictive of disease transmission and improve significantly on standard school term time and weather covariates. Further, combining seasonal and spatial data on travel from mobile phone data allows us to characterize seasonal fluctuations in risk across Kenya and produce dynamic importation risk maps for rubella. Mobile phone data therefore offer a valuable previously unidentified source of data for measuring key drivers of seasonal epidemics. PMID- 26283350 TI - Human hippocampus represents space and time during retrieval of real-world memories. AB - Memory stretches over a lifetime. In controlled laboratory settings, the hippocampus and other medial temporal lobe brain structures have been shown to represent space and time on the scale of meters and seconds. It remains unclear whether the hippocampus also represents space and time over the longer scales necessary for human episodic memory. We recorded neural activity while participants relived their own experiences, cued by photographs taken with a custom lifelogging device. We found that the left anterior hippocampus represents space and time for a month of remembered events occurring over distances of up to 30 km. Although previous studies have identified similar drifts in representational similarity across space or time over the relatively brief time scales (seconds to minutes) that characterize individual episodic memories, our results provide compelling evidence that a similar pattern of spatiotemporal organization also exists for organizing distinct memories that are distant in space and time. These results further support the emerging view that the anterior, as opposed to posterior, hippocampus integrates distinct experiences, thereby providing a scaffold for encoding and retrieval of autobiographical memories on the scale of our lives. PMID- 26283351 TI - Teaching critical thinking. AB - The ability to make decisions based on data, with its inherent uncertainties and variability, is a complex and vital skill in the modern world. The need for such quantitative critical thinking occurs in many different contexts, and although it is an important goal of education, that goal is seldom being achieved. We argue that the key element for developing this ability is repeated practice in making decisions based on data, with feedback on those decisions. We demonstrate a structure for providing suitable practice that can be applied in any instructional setting that involves the acquisition of data and relating that data to scientific models. This study reports the results of applying that structure in an introductory physics laboratory course. Students in an experimental condition were repeatedly instructed to make and act on quantitative comparisons between datasets, and between data and models, an approach that is common to all science disciplines. These instructions were slowly faded across the course. After the instructions had been removed, students in the experimental condition were 12 times more likely to spontaneously propose or make changes to improve their experimental methods than a control group, who performed traditional experimental activities. The students in the experimental condition were also four times more likely to identify and explain a limitation of a physical model using their data. Students in the experimental condition also showed much more sophisticated reasoning about their data. These differences between the groups were seen to persist into a subsequent course taken the following year. PMID- 26283352 TI - Neural systems supporting linguistic structure, linguistic experience, and symbolic communication in sign language and gesture. AB - Sign languages used by deaf communities around the world possess the same structural and organizational properties as spoken languages: In particular, they are richly expressive and also tightly grammatically constrained. They therefore offer the opportunity to investigate the extent to which the neural organization for language is modality independent, as well as to identify ways in which modality influences this organization. The fact that sign languages share the visual-manual modality with a nonlinguistic symbolic communicative system-gesture further allows us to investigate where the boundaries lie between language and symbolic communication more generally. In the present study, we had three goals: to investigate the neural processing of linguistic structure in American Sign Language (using verbs of motion classifier constructions, which may lie at the boundary between language and gesture); to determine whether we could dissociate the brain systems involved in deriving meaning from symbolic communication (including both language and gesture) from those specifically engaged by linguistically structured content (sign language); and to assess whether sign language experience influences the neural systems used for understanding nonlinguistic gesture. The results demonstrated that even sign language constructions that appear on the surface to be similar to gesture are processed within the left-lateralized frontal-temporal network used for spoken languages supporting claims that these constructions are linguistically structured. Moreover, although nonsigners engage regions involved in human action perception to process communicative, symbolic gestures, signers instead engage parts of the language-processing network-demonstrating an influence of experience on the perception of nonlinguistic stimuli. PMID- 26283354 TI - Activation of Big Grain1 significantly improves grain size by regulating auxin transport in rice. AB - Grain size is one of the key factors determining grain yield. However, it remains largely unknown how grain size is regulated by developmental signals. Here, we report the identification and characterization of a dominant mutant big grain1 (Bg1-D) that shows an extra-large grain phenotype from our rice T-DNA insertion population. Overexpression of BG1 leads to significantly increased grain size, and the severe lines exhibit obviously perturbed gravitropism. In addition, the mutant has increased sensitivities to both auxin and N-1-naphthylphthalamic acid, an auxin transport inhibitor, whereas knockdown of BG1 results in decreased sensitivities and smaller grains. Moreover, BG1 is specifically induced by auxin treatment, preferentially expresses in the vascular tissue of culms and young panicles, and encodes a novel membrane-localized protein, strongly suggesting its role in regulating auxin transport. Consistent with this finding, the mutant has increased auxin basipetal transport and altered auxin distribution, whereas the knockdown plants have decreased auxin transport. Manipulation of BG1 in both rice and Arabidopsis can enhance plant biomass, seed weight, and yield. Taking these data together, we identify a novel positive regulator of auxin response and transport in a crop plant and demonstrate its role in regulating grain size, thus illuminating a new strategy to improve plant productivity. PMID- 26283353 TI - Brain system for mental orientation in space, time, and person. AB - Orientation is a fundamental mental function that processes the relations between the behaving self to space (places), time (events), and person (people). Behavioral and neuroimaging studies have hinted at interrelations between processing of these three domains. To unravel the neurocognitive basis of orientation, we used high-resolution 7T functional MRI as 16 subjects compared their subjective distance to different places, events, or people. Analysis at the individual-subject level revealed cortical activation related to orientation in space, time, and person in a precisely localized set of structures in the precuneus, inferior parietal, and medial frontal cortex. Comparison of orientation domains revealed a consistent order of cortical activity inside the precuneus and inferior parietal lobes, with space orientation activating posterior regions, followed anteriorly by person and then time. Core regions at the precuneus and inferior parietal lobe were activated for multiple orientation domains, suggesting also common processing for orientation across domains. The medial prefrontal cortex showed a posterior activation for time and anterior for person. Finally, the default-mode network, identified in a separate resting-state scan, was active for all orientation domains and overlapped mostly with person orientation regions. These findings suggest that mental orientation in space, time, and person is managed by a specific brain system with a highly ordered internal organization, closely related to the default-mode network. PMID- 26283355 TI - Common gamma-chain blocking peptide reduces in vitro immune activation markers in HTLV-1-associated myelopathy/tropical spastic paraparesis. AB - Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive inflammatory myelopathy occurring in a subset of HTLV-1-infected individuals. Despite advances in understanding its immunopathogenesis, an effective treatment remains to be found. IL-2 and IL-15, members of the gamma chain (gammac) family of cytokines, are prominently deregulated in HAM/TSP and underlie many of the characteristic immune abnormalities, such as spontaneous lymphocyte proliferation (SP), increased STAT5 phosphorylation in the lymphocytes, and increased frequency and cytotoxicity of virus-specific cytotoxic CD8(+) T lymphocytes (CTLs). In this study, we describe a novel immunomodulatory strategy consisting of selective blockade of certain gammac family cytokines, including IL-2 and IL-15, with a gammac antagonistic peptide. In vitro, a PEGylated form of the peptide, named BNZ132-1-40, reduced multiple immune activation markers such as SP, STAT5 phosphorylation, spontaneous degranulation of CD8(+) T cells, and the frequency of transactivator protein (Tax)-specific CD8(+) CTLs, thought to be major players in the immunopathogenesis of the disease. This strategy is thus a promising therapeutic approach to HAM/TSP with the potential of being more effective than single monoclonal antibodies targeting either IL-2 or IL-15 receptors and safer than inhibitors of downstream signaling molecules such as JAK1 inhibitors. Finally, selective cytokine blockade with antagonistic peptides might be applicable to multiple other conditions in which cytokines are pathogenic. PMID- 26283357 TI - Temporal and spatial variation of the human microbiota during pregnancy. AB - Despite the critical role of the human microbiota in health, our understanding of microbiota compositional dynamics during and after pregnancy is incomplete. We conducted a case-control study of 49 pregnant women, 15 of whom delivered preterm. From 40 of these women, we analyzed bacterial taxonomic composition of 3,767 specimens collected prospectively and weekly during gestation and monthly after delivery from the vagina, distal gut, saliva, and tooth/gum. Linear mixed effects modeling, medoid-based clustering, and Markov chain modeling were used to analyze community temporal trends, community structure, and vaginal community state transitions. Microbiota community taxonomic composition and diversity remained remarkably stable at all four body sites during pregnancy (P > 0.05 for trends over time). Prevalence of a Lactobacillus-poor vaginal community state type (CST 4) was inversely correlated with gestational age at delivery (P = 0.0039). Risk for preterm birth was more pronounced for subjects with CST 4 accompanied by elevated Gardnerella or Ureaplasma abundances. This finding was validated with a set of 246 vaginal specimens from nine women (four of whom delivered preterm). Most women experienced a postdelivery disturbance in the vaginal community characterized by a decrease in Lactobacillus species and an increase in diverse anaerobes such as Peptoniphilus, Prevotella, and Anaerococcus species. This disturbance was unrelated to gestational age at delivery and persisted for up to 1 y. These findings have important implications for predicting premature labor, a major global health problem, and for understanding the potential impact of a persistent, altered postpartum microbiota on maternal health, including outcomes of pregnancies following short interpregnancy intervals. PMID- 26283358 TI - New approach for optimal electricity planning and dispatching with hourly time scale air quality and health considerations. AB - Integrating accurate air quality modeling with decision making is hampered by complex atmospheric physics and chemistry and its coupling with atmospheric transport. Existing approaches to model the physics and chemistry accurately lead to significant computational burdens in computing the response of atmospheric concentrations to changes in emissions profiles. By integrating a reduced form of a fully coupled atmospheric model within a unit commitment optimization model, we allow, for the first time to our knowledge, a fully dynamical approach toward electricity planning that accurately and rapidly minimizes both cost and health impacts. The reduced-form model captures the response of spatially resolved air pollutant concentrations to changes in electricity-generating plant emissions on an hourly basis with accuracy comparable to a comprehensive air quality model. The integrated model allows for the inclusion of human health impacts into cost based decisions for power plant operation. We use the new capability in a case study of the state of Georgia over the years of 2004-2011, and show that a shift in utilization among existing power plants during selected hourly periods could have provided a health cost savings of $175.9 million dollars for an additional electricity generation cost of $83.6 million in 2007 US dollars (USD2007). The case study illustrates how air pollutant health impacts can be cost-effectively minimized by intelligently modulating power plant operations over multihour periods, without implementing additional emissions control technologies. PMID- 26283359 TI - The massacre mass grave of Schoneck-Kilianstadten reveals new insights into collective violence in Early Neolithic Central Europe. AB - Conflict and warfare are central but also disputed themes in discussions about the European Neolithic. Although a few recent population studies provide broad overviews, only a very limited number of currently known key sites provide precise insights into moments of extreme and mass violence and their impact on Neolithic societies. The massacre sites of Talheim, Germany, and Asparn/Schletz, Austria, have long been the focal points around which hypotheses concerning a final lethal crisis of the first Central European farmers of the Early Neolithic Linearbandkeramik Culture (LBK) have concentrated. With the recently examined LBK mass grave site of Schoneck-Kilianstadten, Germany, we present new conclusive and indisputable evidence for another massacre, adding new data to the discussion of LBK violence patterns. At least 26 individuals were violently killed by blunt force and arrow injuries before being deposited in a commingled mass grave. Although the absence and possible abduction of younger females has been suggested for other sites previously, a new violence-related pattern was identified here: the intentional and systematic breaking of lower limbs. The abundance of the identified perimortem fractures clearly indicates torture and/or mutilation of the victims. The new evidence presented here for unequivocal lethal violence on a large scale is put into perspective for the Early Neolithic of Central Europe and, in conjunction with previous results, indicates that massacres of entire communities were not isolated occurrences but rather were frequent features of the last phases of the LBK. PMID- 26283356 TI - Transcription factors FOXA1 and FOXA2 maintain dopaminergic neuronal properties and control feeding behavior in adult mice. AB - Midbrain dopaminergic (mDA) neurons are implicated in cognitive functions, neuropsychiatric disorders, and pathological conditions; hence understanding genes regulating their homeostasis has medical relevance. Transcription factors FOXA1 and FOXA2 (FOXA1/2) are key determinants of mDA neuronal identity during development, but their roles in adult mDA neurons are unknown. We used a conditional knockout strategy to specifically ablate FOXA1/2 in mDA neurons of adult mice. We show that deletion of Foxa1/2 results in down-regulation of tyrosine hydroxylase, the rate-limiting enzyme of dopamine (DA) biosynthesis, specifically in dopaminergic neurons of the substantia nigra pars compacta (SNc). In addition, DA synthesis and striatal DA transmission were reduced after Foxa1/2 deletion. Furthermore, the burst-firing activity characteristic of SNc mDA neurons was drastically reduced in the absence of FOXA1/2. These molecular and functional alterations lead to a severe feeding deficit in adult Foxa1/2 mutant mice, independently of motor control, which could be rescued by L-DOPA treatment. FOXA1/2 therefore control the maintenance of molecular and physiological properties of SNc mDA neurons and impact on feeding behavior in adult mice. PMID- 26283360 TI - Increasing disparities between resource inputs and outcomes, as measured by certain health deliverables, in biomedical research. AB - Society makes substantial investments in biomedical research, searching for ways to better human health. The product of this research is principally information published in scientific journals. Continued investment in science relies on society's confidence in the accuracy, honesty, and utility of research results. A recent focus on productivity has dominated the competitive evaluation of scientists, creating incentives to maximize publication numbers, citation counts, and publications in high-impact journals. Some studies have also suggested a decreasing quality in the published literature. The efficiency of society's investments in biomedical research, in terms of improved health outcomes, has not been studied. We show that biomedical research outcomes over the last five decades, as estimated by both life expectancy and New Molecular Entities approved by the Food and Drug Administration, have remained relatively constant despite rising resource inputs and scientific knowledge. Research investments by the National Institutes of Health over this time correlate with publication and author numbers but not with the numerical development of novel therapeutics. We consider several possibilities for the growing input-outcome disparity including the prior elimination of easier research questions, increasing specialization, overreliance on reductionism, a disproportionate emphasis on scientific outputs, and other negative pressures on the scientific enterprise. Monitoring the efficiency of research investments in producing positive societal outcomes may be a useful mechanism for weighing the efficacy of reforms to the scientific enterprise. Understanding the causes of the increasing input-outcome disparity in biomedical research may improve society's confidence in science and provide support for growing future research investments. PMID- 26283361 TI - Neural microgenesis of personally familiar face recognition. AB - Despite a wealth of information provided by neuroimaging research, the neural basis of familiar face recognition in humans remains largely unknown. Here, we isolated the discriminative neural responses to unfamiliar and familiar faces by slowly increasing visual information (i.e., high-spatial frequencies) to progressively reveal faces of unfamiliar or personally familiar individuals. Activation in ventral occipitotemporal face-preferential regions increased with visual information, independently of long-term face familiarity. In contrast, medial temporal lobe structures (perirhinal cortex, amygdala, hippocampus) and anterior inferior temporal cortex responded abruptly when sufficient information for familiar face recognition was accumulated. These observations suggest that following detailed analysis of individual faces in core posterior areas of the face-processing network, familiar face recognition emerges categorically in medial temporal and anterior regions of the extended cortical face network. PMID- 26283362 TI - Independent regulation of vertebral number and vertebral identity by microRNA-196 paralogs. AB - The Hox genes play a central role in patterning the embryonic anterior-to posterior axis. An important function of Hox activity in vertebrates is the specification of different vertebral morphologies, with an additional role in axis elongation emerging. The miR-196 family of microRNAs (miRNAs) are predicted to extensively target Hox 3' UTRs, although the full extent to which miR-196 regulates Hox expression dynamics and influences mammalian development remains to be elucidated. Here we used an extensive allelic series of mouse knockouts to show that the miR-196 family of miRNAs is essential both for properly patterning vertebral identity at different axial levels and for modulating the total number of vertebrae. All three miR-196 paralogs, 196a1, 196a2, and 196b, act redundantly to pattern the midthoracic region, whereas 196a2 and 196b have an additive role in controlling the number of rib-bearing vertebra and positioning of the sacrum. Independent of this, 196a1, 196a2, and 196b act redundantly to constrain total vertebral number. Loss of miR-196 leads to a collective up-regulation of numerous trunk Hox target genes with a concomitant delay in activation of caudal Hox genes, which are proposed to signal the end of axis extension. Additionally, we identified altered molecular signatures associated with the Wnt, Fgf, and Notch/segmentation pathways and demonstrate that miR-196 has the potential to regulate Wnt activity by multiple mechanisms. By feeding into, and thereby integrating, multiple genetic networks controlling vertebral number and identity, miR-196 is a critical player defining axial formulae. PMID- 26283364 TI - Structural basis for inhibition of TLR2 by staphylococcal superantigen-like protein 3 (SSL3). AB - Toll-like receptors (TLRs) are crucial in innate recognition of invading micro organisms and their subsequent clearance. Bacteria are not passive bystanders and have evolved complex evasion mechanisms. Staphylococcus aureus secretes a potent TLR2 antagonist, staphylococcal superantigen-like protein 3 (SSL3), which prevents receptor stimulation by pathogen-associated lipopeptides. Here, we present crystal structures of SSL3 and its complex with TLR2. The structure reveals that formation of the specific inhibitory complex is predominantly mediated by hydrophobic contacts between SSL3 and TLR2 and does not involve interaction of TLR2-glycans with the conserved Lewis(X) binding site of SSL3. In the complex, SSL3 partially covers the entrance to the lipopeptide binding pocket in TLR2, reducing its size by ~50%. We show that this is sufficient to inhibit binding of agonist Pam2CSK4 effectively, yet allows SSL3 to bind to an already formed TLR2-Pam2CSK4 complex. The binding site of SSL3 overlaps those of TLR2 dimerization partners TLR1 and TLR6 extensively. Combined, our data reveal a robust dual mechanism in which SSL3 interferes with TLR2 activation at two stages: by binding to TLR2, it blocks ligand binding and thus inhibits activation. Second, by interacting with an already formed TLR2-lipopeptide complex, it prevents TLR heterodimerization and downstream signaling. PMID- 26283363 TI - Viral fusion protein transmembrane domain adopts beta-strand structure to facilitate membrane topological changes for virus-cell fusion. AB - The C-terminal transmembrane domain (TMD) of viral fusion proteins such as HIV gp41 and influenza hemagglutinin (HA) is traditionally viewed as a passive alpha helical anchor of the protein to the virus envelope during its merger with the cell membrane. The conformation, dynamics, and lipid interaction of these fusion protein TMDs have so far eluded high-resolution structure characterization because of their highly hydrophobic nature. Using magic-angle-spinning solid state NMR spectroscopy, we show that the TMD of the parainfluenza virus 5 (PIV5) fusion protein adopts lipid-dependent conformations and interactions with the membrane and water. In phosphatidylcholine (PC) and phosphatidylglycerol (PG) membranes, the TMD is predominantly alpha-helical, but in phosphatidylethanolamine (PE) membranes, the TMD changes significantly to the beta-strand conformation. Measured order parameters indicate that the strand segments are immobilized and thus oligomerized. (31)P NMR spectra and small-angle X-ray scattering (SAXS) data show that this beta-strand-rich conformation converts the PE membrane to a bicontinuous cubic phase, which is rich in negative Gaussian curvature that is characteristic of hemifusion intermediates and fusion pores. (1)H-(31)P 2D correlation spectra and (2)H spectra show that the PE membrane with or without the TMD is much less hydrated than PC and PG membranes, suggesting that the TMD works with the natural dehydration tendency of PE to facilitate membrane merger. These results suggest a new viral-fusion model in which the TMD actively promotes membrane topological changes during fusion using the beta-strand as the fusogenic conformation. PMID- 26283365 TI - Transmembrane signaling in the sensor kinase DcuS of Escherichia coli: A long range piston-type displacement of transmembrane helix 2. AB - The C4-dicarboxylate sensor kinase DcuS is membrane integral because of the transmembrane (TM) helices TM1 and TM2. Fumarate-induced movement of the helices was probed in vivo by Cys accessibility scanning at the membrane-water interfaces after activation of DcuS by fumarate at the periplasmic binding site. TM1 was inserted with amino acid residues 21-41 in the membrane in both the fumarate activated (ON) and inactive (OFF) states. In contrast, TM2 was inserted with residues 181-201 in the OFF state and residues 185-205 in the ON state. Replacement of Trp 185 by an Arg residue caused displacement of TM2 toward the outside of the membrane and a concomitant induction of the ON state. Results from Cys cross-linking of TM2/TM2' in the DcuS homodimer excluded rotation; thus, data from accessibility changes of TM2 upon activation, either by ligand binding or by mutation of TM2, and cross-linking of TM2 and the connected region in the periplasm suggest a piston-type shift of TM2 by four residues to the periplasm upon activation (or fumarate binding). This mode of function is supported by the suggestion from energetic calculations of two preferred positions for TM2 insertion in the membrane. The shift of TM2 by four residues (or 4-6 A) toward the periplasm upon activation is complementary to the periplasmic displacement of 3-4 A of the C-terminal part of the periplasmic ligand-binding domain upon ligand occupancy in the citrate-binding domain in the homologous CitA sensor kinase. PMID- 26283366 TI - Multiple component networks support working memory in prefrontal cortex. AB - Lateral prefrontal cortex (PFC) is regarded as the hub of the brain's working memory (WM) system, but it remains unclear whether WM is supported by a single distributed network or multiple specialized network components in this region. To investigate this problem, we recorded from neurons in PFC while monkeys made delayed eye movements guided by memory or vision. We show that neuronal responses during these tasks map to three anatomically specific modes of persistent activity. The first two modes encode early and late forms of information storage, whereas the third mode encodes response preparation. Neurons that reflect these modes are concentrated at different anatomical locations in PFC and exhibit distinct patterns of coordinated firing rates and spike timing during WM, consistent with distinct networks. These findings support multiple component models of WM and consequently predict distinct failures that could contribute to neurologic dysfunction. PMID- 26283367 TI - Functional metagenomic discovery of bacterial effectors in the human microbiome and isolation of commendamide, a GPCR G2A/132 agonist. AB - The trillions of bacteria that make up the human microbiome are believed to encode functions that are important to human health; however, little is known about the specific effectors that commensal bacteria use to interact with the human host. Functional metagenomics provides a systematic means of surveying commensal DNA for genes that encode effector functions. Here, we examine 3,000 Mb of metagenomic DNA cloned from three phenotypically distinct patients for effectors that activate NF-kappaB, a transcription factor known to play a central role in mediating responses to environmental stimuli. This screen led to the identification of 26 unique commensal bacteria effector genes (Cbegs) that are predicted to encode proteins with diverse catabolic, anabolic, and ligand-binding functions and most frequently interact with either glycans or lipids. Detailed analysis of one effector gene family (Cbeg12) recovered from all three patient libraries found that it encodes for the production of N-acyl-3-hydroxypalmitoyl glycine (commendamide). This metabolite was also found in culture broth from the commensal bacterium Bacteroides vulgatus, which harbors a gene highly similar to Cbeg12. Commendamide resembles long-chain N-acyl-amides that function as mammalian signaling molecules through activation of G-protein-coupled receptors (GPCRs), which led us to the observation that commendamide activates the GPCR G2A/GPR132. G2A has been implicated in disease models of autoimmunity and atherosclerosis. This study shows the utility of functional metagenomics for identifying potential mechanisms used by commensal bacteria for host interactions and outlines a functional metagenomics-based pipeline for the systematic identification of diverse commensal bacteria effectors that impact host cellular functions. PMID- 26283368 TI - Regulated proteolysis of a cross-link-specific peptidoglycan hydrolase contributes to bacterial morphogenesis. AB - Bacterial growth and morphogenesis are intimately coupled to expansion of peptidoglycan (PG), an extensively cross-linked macromolecule that forms a protective mesh-like sacculus around the cytoplasmic membrane. Growth of the PG sacculus is a dynamic event requiring the concerted action of hydrolases that cleave the cross-links for insertion of new material and synthases that catalyze cross-link formation; however, the factors that regulate PG expansion during bacterial growth are poorly understood. Here, we show that the PG hydrolase MepS (formerly Spr), which is specific to cleavage of cross-links during PG expansion in Escherichia coli, is modulated by proteolysis. Using combined genetic, molecular, and biochemical approaches, we demonstrate that MepS is rapidly degraded by a proteolytic system comprising an outer membrane lipoprotein of unknown function, NlpI, and a periplasmic protease, Prc (or Tsp). In summary, our results indicate that the NlpI-Prc system contributes to growth and enlargement of the PG sacculus by modulating the cellular levels of the cross-link-cleaving hydrolase MepS. Overall, this study signifies the importance of PG cross-link cleavage and its regulation in bacterial cell wall biogenesis. PMID- 26283369 TI - Talin determines the nanoscale architecture of focal adhesions. AB - Insight into how molecular machines perform their biological functions depends on knowledge of the spatial organization of the components, their connectivity, geometry, and organizational hierarchy. However, these parameters are difficult to determine in multicomponent assemblies such as integrin-based focal adhesions (FAs). We have previously applied 3D superresolution fluorescence microscopy to probe the spatial organization of major FA components, observing a nanoscale stratification of proteins between integrins and the actin cytoskeleton. Here we combine superresolution imaging techniques with a protein engineering approach to investigate how such nanoscale architecture arises. We demonstrate that talin plays a key structural role in regulating the nanoscale architecture of FAs, akin to a molecular ruler. Talin diagonally spans the FA core, with its N terminus at the membrane and C terminus demarcating the FA/stress fiber interface. In contrast, vinculin is found to be dispensable for specification of FA nanoscale architecture. Recombinant analogs of talin with modified lengths recapitulated its polarized orientation but altered the FA/stress fiber interface in a linear manner, consistent with its modular structure, and implicating the integrin-talin actin complex as the primary mechanical linkage in FAs. Talin was found to be ~97 nm in length and oriented at ~15 degrees relative to the plasma membrane. Our results identify talin as the primary determinant of FA nanoscale organization and suggest how multiple cellular forces may be integrated at adhesion sites. PMID- 26283370 TI - Homeostasis and the glycogen shunt explains aerobic ethanol production in yeast. AB - Aerobic glycolysis in yeast and cancer cells produces pyruvate beyond oxidative needs, a paradox noted by Warburg almost a century ago. To address this question, we reanalyzed extensive measurements from (13)C magnetic resonance spectroscopy of yeast glycolysis and the coupled pathways of futile cycling and glycogen and trehalose synthesis (which we refer to as the glycogen shunt). When yeast are given a large glucose load under aerobic conditions, the fluxes of these pathways adapt to maintain homeostasis of glycolytic intermediates and ATP. The glycogen shunt uses glycolytic ATP to store glycolytic intermediates as glycogen and trehalose, generating pyruvate and ethanol as byproducts. This conclusion is supported by studies of yeast with a partial block in the glycogen shunt due to the cif mutation, which found that when challenged with glucose, the yeast cells accumulate glycolytic intermediates and ATP, which ultimately leads to cell death. The control of the relative fluxes, which is critical to maintain homeostasis, is most likely exerted by the enzymes pyruvate kinase and fructose bisphosphatase. The kinetic properties of yeast PK and mammalian PKM2, the isoform found in cancer, are similar, suggesting that the same mechanism may exist in cancer cells, which, under these conditions, could explain their excess lactate generation. The general principle that homeostasis of metabolite and ATP concentrations is a critical requirement for metabolic function suggests that enzymes and pathways that perform this critical role could be effective drug targets in cancer and other diseases. PMID- 26283371 TI - Highly activated RNA silencing via strong induction of dicer by one virus can interfere with the replication of an unrelated virus. AB - Viruses often coinfect single host organisms in nature. Depending on the combination of viruses in such coinfections, the interplay between them may be synergistic, apparently neutral with no effect on each other, or antagonistic. RNA silencing is responsible for many cases of interference or cross-protection between viruses, but such antagonistic interactions are usually restricted to closely related strains of the same viral species. In this study, we present an unprecedented example of RNA silencing-mediated one-way interference between unrelated viruses in a filamentous model fungus, Cryphonectria parasitica. The replication of Rosellinia necatrix victorivirus 1 (RnVV1; Totiviridae) was strongly impaired by coinfection with the prototypic member of the genus Mycoreovirus (MyRV1) or a mutant of the prototype hypovirus (Cryphonectria hypovirus 1, CHV1) lacking the RNA silencing suppressor (CHV1-Deltap69). This interference was associated with marked transcriptional induction of key genes in antiviral RNA silencing, dicer-like 2 (dcl2) and argonaute-like 2 (agl2), following MyRV1 or CHV1-Deltap69 infection. Interestingly, the inhibition of RnVV1 replication was reproduced when the levels of dcl2 and agl2 transcripts were elevated by transgenic expression of a hairpin construct of an endogenous C. parasitica gene. Disruption of dcl2 completely abolished the interference, whereas that of agl2 did not always lead to its abolishment, suggesting more crucial roles of dcl2 in antiviral defense. Taken altogether, these results demonstrated the susceptible nature of RnVV1 to the antiviral silencing in C. parasitica activated by distinct viruses or transgene-derived double-stranded RNAs and provide insight into the potential for broad-spectrum virus control mediated by RNA silencing. PMID- 26283372 TI - Amplifying the response of soft actuators by harnessing snap-through instabilities. AB - Soft, inflatable segments are the active elements responsible for the actuation of soft machines and robots. Although current designs of fluidic actuators achieve motion with large amplitudes, they require large amounts of supplied volume, limiting their speed and compactness. To circumvent these limitations, here we embrace instabilities and show that they can be exploited to amplify the response of the system. By combining experimental and numerical tools we design and construct fluidic actuators in which snap-through instabilities are harnessed to generate large motion, high forces, and fast actuation at constant volume. Our study opens avenues for the design of the next generation of soft actuators and robots in which small amounts of volume are sufficient to achieve significant ranges of motion. PMID- 26283373 TI - Transforming growth factor-beta signaling is constantly shaping memory T-cell population. AB - The long-term maintenance of memory T cells is essential for successful vaccines. Both the quantity and the quality of the memory T-cell population must be maintained. The signals that control the maintenance of memory T cells remain incompletely identified. Here we used two genetic models to show that continuous transforming growth factor-beta signaling to antigen-specific T cells is required for the differentiation and maintenance of memory CD8(+) T cells. In addition, both infection-induced and microbiota-induced inflammation impact the phenotypic and functional identity of memory CD8(+) T cells. PMID- 26283374 TI - Screen for multi-SUMO-binding proteins reveals a multi-SIM-binding mechanism for recruitment of the transcriptional regulator ZMYM2 to chromatin. AB - Protein SUMOylation has emerged as an important regulatory event, particularly in nuclear processes such as transcriptional control and DNA repair. In this context, small ubiquitin-like modifier (SUMO) often provides a binding platform for the recruitment of proteins via their SUMO-interacting motifs (SIMs). Recent discoveries point to an important role for multivalent SUMO binding through multiple SIMs in the binding partner as exemplified by poly-SUMOylation acting as a binding platform for ubiquitin E3 ligases such as ring finger protein 4. Here, we have investigated whether other types of protein are recruited through multivalent SUMO interactions. We have identified dozens of proteins that bind to multi-SUMO platforms, thereby uncovering a complex potential regulatory network. Multi-SUMO binding is mediated through multi-SIM modules, and the functional importance of these interactions is demonstrated for the transcriptional corepressor ZMYM2/ZNF198 where its multi-SUMO-binding activity is required for its recruitment to chromatin. PMID- 26283375 TI - Electrocorticography reveals the temporal dynamics of posterior parietal cortical activity during recognition memory decisions. AB - Theories of the neurobiology of episodic memory predominantly focus on the contributions of medial temporal lobe structures, based on extensive lesion, electrophysiological, and imaging evidence. Against this backdrop, functional neuroimaging data have unexpectedly implicated left posterior parietal cortex (PPC) in episodic retrieval, revealing distinct activation patterns in PPC subregions as humans make memory-related decisions. To date, theorizing about the functional contributions of PPC has been hampered by the absence of information about the temporal dynamics of PPC activity as retrieval unfolds. Here, we leveraged electrocorticography to examine the temporal profile of high gamma power (HGP) in dorsal PPC subregions as participants made old/new recognition memory decisions. A double dissociation in memory-related HGP was observed, with activity in left intraparietal sulcus (IPS) and left superior parietal lobule (SPL) differing in time and sign for recognized old items (Hits) and correctly rejected novel items (CRs). Specifically, HGP in left IPS increased for Hits 300 700 ms poststimulus onset, and decayed to baseline ~200 ms preresponse. By contrast, HGP in left SPL increased for CRs early after stimulus onset (200-300 ms) and late in the memory decision (from 700 ms to response). These memory related effects were unique to left PPC, as they were not observed in right PPC. Finally, memory-related HGP in left IPS and SPL was sufficiently reliable to enable brain-based decoding of the participant's memory state at the single-trial level, using multivariate pattern classification. Collectively, these data provide insights into left PPC temporal dynamics as humans make recognition memory decisions. PMID- 26283376 TI - SUMOylation of phytochrome-B negatively regulates light-induced signaling in Arabidopsis thaliana. AB - The red/far red light absorbing photoreceptor phytochrome-B (phyB) cycles between the biologically inactive (Pr, lambdamax, 660 nm) and active (Pfr; lambdamax, 730 nm) forms and functions as a light quality and quantity controlled switch to regulate photomorphogenesis in Arabidopsis. At the molecular level, phyB interacts in a conformation-dependent fashion with a battery of downstream regulatory proteins, including PHYTOCHROME INTERACTING FACTOR transcription factors, and by modulating their activity/abundance, it alters expression patterns of genes underlying photomorphogenesis. Here we report that the small ubiquitin-like modifier (SUMO) is conjugated (SUMOylation) to the C terminus of phyB; the accumulation of SUMOylated phyB is enhanced by red light and displays a diurnal pattern in plants grown under light/dark cycles. Our data demonstrate that (i) transgenic plants expressing the mutant phyB(Lys996Arg)-YFP photoreceptor are hypersensitive to red light, (ii) light-induced SUMOylation of the mutant phyB is drastically decreased compared with phyB-YFP, and (iii) SUMOylation of phyB inhibits binding of PHYTOCHROME INTERACTING FACTOR 5 to phyB Pfr. In addition, we show that OVERLY TOLERANT TO SALT 1 (OTS1) de-SUMOylates phyB in vitro, it interacts with phyB in vivo, and the ots1/ots2 mutant is hyposensitive to red light. Taken together, we conclude that SUMOylation of phyB negatively regulates light signaling and it is mediated, at least partly, by the action of OTS SUMO proteases. PMID- 26283377 TI - Unraveling the mechanism of selective ion transport in hydrophobic subnanometer channels. AB - Recently reported synthetic organic nanopore (SONP) can mimic a key feature of natural ion channels, i.e., selective ion transport. However, the physical mechanism underlying the K(+)/Na(+) selectivity for the SONPs is dramatically different from that of natural ion channels. To achieve a better understanding of the selective ion transport in hydrophobic subnanometer channels in general and SONPs in particular, we perform a series of ab initio molecular dynamics simulations to investigate the diffusivity of aqua Na(+) and K(+) ions in two prototype hydrophobic nanochannels: (i) an SONP with radius of 3.2 A, and (ii) single-walled carbon nanotubes (CNTs) with radii of 3-5 A (these radii are comparable to those of the biological potassium K(+) channels). We find that the hydration shell of aqua Na(+) ion is smaller than that of aqua K(+) ion but notably more structured and less yielding. The aqua ions do not lower the diffusivity of water molecules in CNTs, but in SONP the diffusivity of aqua ions (Na(+) in particular) is strongly suppressed due to the rugged inner surface. Moreover, the aqua Na(+) ion requires higher formation energy than aqua K(+) ion in the hydrophobic nanochannels. As such, we find that the ion (K(+) vs. Na(+)) selectivity of the (8, 8) CNT is ~20* higher than that of SONP. Hence, the (8, 8) CNT is likely the most efficient artificial K(+) channel due in part to its special interior environment in which Na(+) can be fully solvated, whereas K(+) cannot. This work provides deeper insights into the physical chemistry behind selective ion transport in nanochannels. PMID- 26283378 TI - Hybrid mimics and hybrid vigor in Arabidopsis. AB - F1 hybrids can outperform their parents in yield and vegetative biomass, features of hybrid vigor that form the basis of the hybrid seed industry. The yield advantage of the F1 is lost in the F2 and subsequent generations. In Arabidopsis, from F2 plants that have a F1-like phenotype, we have by recurrent selection produced pure breeding F5/F6 lines, hybrid mimics, in which the characteristics of the F1 hybrid are stabilized. These hybrid mimic lines, like the F1 hybrid, have larger leaves than the parent plant, and the leaves have increased photosynthetic cell numbers, and in some lines, increased size of cells, suggesting an increased supply of photosynthate. A comparison of the differentially expressed genes in the F1 hybrid with those of eight hybrid mimic lines identified metabolic pathways altered in both; these pathways include down regulation of defense response pathways and altered abiotic response pathways. F6 hybrid mimic lines are mostly homozygous at each locus in the genome and yet retain the large F1-like phenotype. Many alleles in the F6 plants, when they are homozygous, have expression levels different to the level in the parent. We consider this altered expression to be a consequence of transregulation of genes from one parent by genes from the other parent. Transregulation could also arise from epigenetic modifications in the F1. The pure breeding hybrid mimics have been valuable in probing the mechanisms of hybrid vigor and may also prove to be useful hybrid vigor equivalents in agriculture. PMID- 26283379 TI - Structural remodeling of bacteriophage T4 and host membranes during infection initiation. AB - The first stages of productive bacteriophage infections of bacterial host cells require efficient adsorption to the cell surface followed by ejection of phage DNA into the host cytoplasm. To achieve this goal, a phage virion must undergo significant structural remodeling. For phage T4, the most obvious change is the contraction of its tail. Here, we use skinny E. coli minicells as a host, along with cryo-electron tomography and mutant phage virions, to visualize key structural intermediates during initiation of T4 infection. We show for the first time that most long tail fibers are folded back against the tail sheath until irreversible adsorption, a feature compatible with the virion randomly walking across the cell surface to find an optimal site for infection. Our data confirm that tail contraction is triggered by structural changes in the baseplate, as intermediates were found with remodeled baseplates and extended tails. After contraction, the tail tube penetrates the host cell periplasm, pausing while it degrades the peptidoglycan layer. Penetration into the host cytoplasm is accompanied by a dramatic local outward curvature of the cytoplasmic membrane as it fuses with the phage tail tip. The baseplate hub protein gp27 and/or the ejected tape measure protein gp29 likely form the transmembrane channel for viral DNA passage into the cell cytoplasm. Building on the wealth of prior biochemical and structural information, this work provides new molecular insights into the mechanistic pathway of T4 phage infection. PMID- 26283380 TI - IRF5 controls both acute and chronic inflammation. AB - Whereas the importance of macrophages in chronic inflammatory diseases is well recognized, there is an increasing awareness that neutrophils may also play an important role. In addition to the well-documented heterogeneity of macrophage phenotypes and functions, neutrophils also show remarkable phenotypic diversity among tissues. Understanding the molecular pathways that control this heterogeneity should provide abundant scope for the generation of more specific and effective therapeutics. We have shown that the transcription factor IFN regulatory factor 5 (IRF5) polarizes macrophages toward an inflammatory phenotype. IRF5 is also expressed in other myeloid cells, including neutrophils, where it was linked to neutrophil function. In this study we explored the role of IRF5 in models of acute inflammation, including antigen-induced inflammatory arthritis and lung injury, both involving an extensive influx of neutrophils. Mice lacking IRF5 accumulate far fewer neutrophils at the site of inflammation due to the reduced levels of chemokines important for neutrophil recruitment, such as the chemokine (C-X-C motif) ligand 1. Furthermore we found that neutrophils express little IRF5 in the joints and that their migratory properties are not affected by the IRF5 deficiency. These studies extend prior ones suggesting that inhibiting IRF5 might be useful for chronic macrophage-induced inflammation and suggest that IRF5 blockade would ameliorate more acute forms of inflammation, including lung injury. PMID- 26283381 TI - MutL traps MutS at a DNA mismatch. AB - DNA mismatch repair (MMR) identifies and corrects errors made during replication. In all organisms except those expressing MutH, interactions between a DNA mismatch, MutS, MutL, and the replication processivity factor (beta-clamp or PCNA) activate the latent MutL endonuclease to nick the error-containing daughter strand. This nick provides an entry point for downstream repair proteins. Despite the well-established significance of strand-specific nicking in MMR, the mechanism(s) by which MutS and MutL assemble on mismatch DNA to allow the subsequent activation of MutL's endonuclease activity by beta-clamp/PCNA remains elusive. In both prokaryotes and eukaryotes, MutS homologs undergo conformational changes to a mobile clamp state that can move away from the mismatch. However, the function of this MutS mobile clamp is unknown. Furthermore, whether the interaction with MutL leads to a mobile MutS-MutL complex or a mismatch-localized complex is hotly debated. We used single molecule FRET to determine that Thermus aquaticus MutL traps MutS at a DNA mismatch after recognition but before its conversion to a sliding clamp. Rather than a clamp, a conformationally dynamic protein assembly typically containing more MutL than MutS is formed at the mismatch. This complex provides a local marker where interaction with beta clamp/PCNA could distinguish parent/daughter strand identity. Our finding that MutL fundamentally changes MutS actions following mismatch detection reframes current thinking on MMR signaling processes critical for genomic stability. PMID- 26283383 TI - Caspary's conductor. PMID- 26283382 TI - Mechanobiological oscillators control lymph flow. AB - The ability of cells to sense and respond to physical forces has been recognized for decades, but researchers are only beginning to appreciate the fundamental importance of mechanical signals in biology. At the larger scale, there has been increased interest in the collective organization of cells and their ability to produce complex, "emergent" behaviors. Often, these complex behaviors result in tissue-level control mechanisms that manifest as biological oscillators, such as observed in fireflies, heartbeats, and circadian rhythms. In many cases, these complex, collective behaviors are controlled--at least in part--by physical forces imposed on the tissue or created by the cells. Here, we use mathematical simulations to show that two complementary mechanobiological oscillators are sufficient to control fluid transport in the lymphatic system: Ca(2+)-mediated contractions can be triggered by vessel stretch, whereas nitric oxide produced in response to the resulting fluid shear stress causes the lymphatic vessel to relax locally. Our model predicts that the Ca(2+) and NO levels alternate spatiotemporally, establishing complementary feedback loops, and that the resulting phasic contractions drive lymph flow. We show that this mechanism is self-regulating and robust over a range of fluid pressure environments, allowing the lymphatic vessels to provide pumping when needed but remain open when flow can be driven by tissue pressure or gravity. Our simulations accurately reproduce the responses to pressure challenges and signaling pathway manipulations observed experimentally, providing an integrated conceptual framework for lymphatic function. PMID- 26283384 TI - Phytochemical diversity drives plant-insect community diversity. AB - What are the ecological causes and consequences of variation in phytochemical diversity within and between plant taxa? Despite decades of natural products discovery by organic chemists and research by chemical ecologists, our understanding of phytochemically mediated ecological processes in natural communities has been restricted to studies of either broad classes of compounds or a small number of well-characterized molecules. Until now, no studies have assessed the ecological causes or consequences of rigorously quantified phytochemical diversity across taxa in natural systems. Consequently, hypotheses that attempt to explain variation in phytochemical diversity among plants remain largely untested. We use spectral data from crude plant extracts to characterize phytochemical diversity in a suite of co-occurring plants in the tropical genus Piper (Piperaceae). In combination with 20 years of data focused on Piper associated insects, we find that phytochemical diversity has a direct and positive effect on the diversity of herbivores but also reduces overall herbivore damage. Elevated chemical diversity is associated with more specialized assemblages of herbivores, and the cascading positive effect of phytochemistry on herbivore enemies is stronger as herbivore diet breadth narrows. These results are consistent with traditional hypotheses that predict positive associations between plant chemical diversity, insect herbivore diversity, and trophic specialization. It is clear from these results that high phytochemical diversity not only enhances the diversity of plant-associated insects but also contributes to the ecological predominance of specialized insect herbivores. PMID- 26283385 TI - Confounding effects of oxygen and temperature on the TEX86 signature of marine Thaumarchaeota. AB - Marine ammonia-oxidizing archaea (AOA) are among the most abundant of marine microorganisms, spanning nearly the entire water column of diverse oceanic provinces. Historical patterns of abundance are preserved in sediments in the form of their distinctive glycerol dibiphytanyl glycerol tetraether (GDGT) membrane lipids. The correlation between the composition of GDGTs in surface sediment and the overlying annual average sea surface temperature forms the basis for a paleotemperature proxy (TEX86) that is used to reconstruct surface ocean temperature as far back as the Middle Jurassic. However, mounting evidence suggests that factors other than temperature could also play an important role in determining GDGT distributions. We here use a study set of four marine AOA isolates to demonstrate that these closely related strains generate different TEX86-temperature relationships and that oxygen (O2) concentration is at least as important as temperature in controlling TEX86 values in culture. All of the four strains characterized showed a unique membrane compositional response to temperature, with TEX86-inferred temperatures varying as much as 12 degrees C from the incubation temperatures. In addition, both linear and nonlinear TEX86 temperature relationships were characteristic of individual strains. Increasing relative abundance of GDGT-2 and GDGT-3 with increasing O2 limitation, at the expense of GDGT-1, led to significant elevations in TEX86-derived temperature. Although the adaptive significance of GDGT compositional changes in response to both temperature and O2 is unclear, this observation necessitates a reassessment of archaeal lipid-based paleotemperature proxies, particularly in records that span low-oxygen events or underlie oxygen minimum zones. PMID- 26283387 TI - Dual allosteric activation mechanisms in monomeric human glucokinase. AB - Cooperativity in human glucokinase (GCK), the body's primary glucose sensor and a major determinant of glucose homeostatic diseases, is fundamentally different from textbook models of allostery because GCK is monomeric and contains only one glucose-binding site. Prior work has demonstrated that millisecond timescale order-disorder transitions within the enzyme's small domain govern cooperativity. Here, using limited proteolysis, we map the site of disorder in unliganded GCK to a 30-residue active-site loop that closes upon glucose binding. Positional randomization of the loop, coupled with genetic selection in a glucokinase deficient bacterium, uncovers a hyperactive GCK variant with substantially reduced cooperativity. Biochemical and structural analysis of this loop variant and GCK variants associated with hyperinsulinemic hypoglycemia reveal two distinct mechanisms of enzyme activation. In alpha-type activation, glucose affinity is increased, the proteolytic susceptibility of the active site loop is suppressed and the (1)H-(13)C heteronuclear multiple quantum coherence (HMQC) spectrum of (13)C-Ile-labeled enzyme resembles the glucose-bound state. In beta type activation, glucose affinity is largely unchanged, proteolytic susceptibility of the loop is enhanced, and the (1)H-(13)C HMQC spectrum reveals no perturbation in ensemble structure. Leveraging both activation mechanisms, we engineer a fully noncooperative GCK variant, whose functional properties are indistinguishable from other hexokinase isozymes, and which displays a 100-fold increase in catalytic efficiency over wild-type GCK. This work elucidates specific structural features responsible for generating allostery in a monomeric enzyme and suggests a general strategy for engineering cooperativity into proteins that lack the structural framework typical of traditional allosteric systems. PMID- 26283386 TI - Electrochemically addressable trisradical rotaxanes organized within a metal organic framework. AB - The organization of trisradical rotaxanes within the channels of a Zr6-based metal-organic framework (NU-1000) has been achieved postsynthetically by solvent assisted ligand incorporation. Robust Zr(IV)-carboxylate bonds are forged between the Zr clusters of NU-1000 and carboxylic acid groups of rotaxane precursors (semirotaxanes) as part of this building block replacement strategy. Ultraviolet visible-near-infrared (UV-Vis-NIR), electron paramagnetic resonance (EPR), and 1H nuclear magnetic resonance (NMR) spectroscopies all confirm the capture of redox active rotaxanes within the mesoscale hexagonal channels of NU-1000. Cyclic voltammetry measurements performed on electroactive thin films of the resulting material indicate that redox-active viologen subunits located on the rotaxane components can be accessed electrochemically in the solid state. In contradistinction to previous methods, this strategy for the incorporation of mechanically interlocked molecules within porous materials circumvents the need for de novo synthesis of a metal-organic framework, making it a particularly convenient approach for the design and creation of solid-state molecular switches and machines. The results presented here provide proof-of-concept for the application of postsynthetic transformations in the integration of dynamic molecular machines with robust porous frameworks. PMID- 26283389 TI - Correction for Xie et al., Assortative mating without assortative preference. PMID- 26283388 TI - Orchestration of three transporters and distinct vascular structures in node for intervascular transfer of silicon in rice. AB - Requirement of mineral elements in different plant tissues is not often consistent with their transpiration rate; therefore, plants have developed systems for preferential distribution of mineral elements to the developing tissues with low transpiration. Here we took silicon (Si) as an example and revealed an efficient system for preferential distribution of Si in the node of rice (Oryza sativa). Rice is able to accumulate more than 10% Si of the dry weight in the husk, which is required for protecting the grains from water loss and pathogen infection. However, it has been unknown for a long time how this hyperaccumulation is achieved. We found that three transporters (Lsi2, Lsi3, and Lsi6) located at the node are involved in the intervascular transfer, which is required for the preferential distribution of Si. Lsi2 was polarly localized to the bundle sheath cell layer around the enlarged vascular bundles, which is next to the xylem transfer cell layer where Lsi6 is localized. Lsi3 was located in the parenchyma tissues between enlarged vascular bundles and diffuse vascular bundles. Similar to Lsi6, knockout of Lsi2 and Lsi3 also resulted in decreased distribution of Si to the panicles but increased Si to the flag leaf. Furthermore, we constructed a mathematical model for Si distribution and revealed that in addition to cooperation of three transporters, an apoplastic barrier localized at the bundle sheath cells and development of the enlarged vascular bundles in node are also required for the hyperaccumulation of Si in rice husk. PMID- 26283390 TI - Kinetics of a Criegee intermediate that would survive high humidity and may oxidize atmospheric SO2. AB - Criegee intermediates are thought to play a role in atmospheric chemistry, in particular, the oxidation of SO2, which produces SO3 and subsequently H2SO4, an important constituent of aerosols and acid rain. However, the impact of such oxidation reactions is affected by the reactions of Criegee intermediates with water vapor, because of high water concentrations in the troposphere. In this work, the kinetics of the reactions of dimethyl substituted Criegee intermediate (CH3)2COO with water vapor and with SO2 were directly measured via UV absorption of (CH3)2COO under near-atmospheric conditions. The results indicate that (i) the water reaction with (CH3)2COO is not fast enough (kH2O < 1.5 * 10(-16) cm(3) s( 1)) to consume atmospheric (CH3)2COO significantly and (ii) (CH3)2COO reacts with SO2 at a near-gas-kinetic-limit rate (kSO2 = 1.3 * 10(-10) cm(3) s(-1)). These observations imply a significant fraction of atmospheric (CH3)2COO may survive under humid conditions and react with SO2, very different from the case of the simplest Criegee intermediate CH2OO, in which the reaction with water dimer predominates in the CH2OO decay under typical tropospheric conditions. In addition, a significant pressure dependence was observed for the reaction of (CH3)2COO with SO2, suggesting the use of low pressure rate may underestimate the impact of this reaction. This work demonstrates that the reactivity of a Criegee intermediate toward water vapor strongly depends on its structure, which will influence the main decay pathways and steady-state concentrations for various Criegee intermediates in the atmosphere. PMID- 26283393 TI - Correction for Tan et al., Fragile charge order in the nonsuperconducting ground state of the underdoped high-temperature superconductors. PMID- 26283392 TI - Structure of BipA in GTP form bound to the ratcheted ribosome. AB - BPI-inducible protein A (BipA) is a member of the family of ribosome-dependent translational GTPase (trGTPase) factors along with elongation factors G and 4 (EF G and EF4). Despite being highly conserved in bacteria and playing a critical role in coordinating cellular responses to environmental changes, its structures (isolated and ribosome bound) remain elusive. Here, we present the crystal structures of apo form and GTP analog, GDP, and guanosine-3',5'-bisdiphosphate (ppGpp)-bound BipA. In addition to having a distinctive domain arrangement, the C terminal domain of BipA has a unique fold. Furthermore, we report the cryo electron microscopy structure of BipA bound to the ribosome in its active GTP form and elucidate the unique structural attributes of BipA interactions with the ribosome and A-site tRNA in the light of its possible function in regulating translation. PMID- 26283391 TI - Metabolic fate of endogenous molecular damage: Urinary glutathione conjugates of DNA-derived base propenals as markers of inflammation. AB - Although mechanistically linked to disease, cellular molecules damaged by endogenous processes have not emerged as significant biomarkers of inflammation and disease risk, due in part to poor understanding of their pharmacokinetic fate from tissue to excretion. Here, we use systematic metabolite profiling to define the fate of a common DNA oxidation product, base propenals, to discover such a biomarker. Based on known chemical reactivity and metabolism in liver cell extracts, 15 candidate metabolites were identified for liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) quantification in urine and bile of rats treated with thymine propenal (Tp). Analysis of urine revealed three metabolites (6% of Tp dose): thymine propenoate and two mercapturate derivatives of glutathione conjugates. Bile contained an additional four metabolites (22% of Tp dose): cysteinylglycine and cysteine derivatives of glutathione adducts. A bis mercapturate was observed in urine of untreated rats and increased approximately three- to fourfold following CCl4-induced oxidative stress or treatment with the DNA-cleaving antitumor agent, bleomycin. Systematic metabolite profiling thus provides evidence for a metabolized DNA damage product as a candidate biomarker of inflammation and oxidative stress in humans. PMID- 26283394 TI - Antagonism screen for inhibitors of bacterial cell wall biogenesis uncovers an inhibitor of undecaprenyl diphosphate synthase. AB - Drug combinations are valuable tools for studying biological systems. Although much attention has been given to synergistic interactions in revealing connections between cellular processes, antagonistic interactions can also have tremendous value in elucidating genetic networks and mechanisms of drug action. Here, we exploit the power of antagonism in a high-throughput screen for molecules that suppress the activity of targocil, an inhibitor of the wall teichoic acid (WTA) flippase in Staphylococcus aureus. Well-characterized antagonism within the WTA biosynthetic pathway indicated that early steps would be sensitive to this screen; however, broader interactions with cell wall biogenesis components suggested that it might capture additional targets. A chemical screening effort using this approach identified clomiphene, a widely used fertility drug, as one such compound. Mechanistic characterization revealed the target was the undecaprenyl diphosphate synthase, an enzyme that catalyzes the synthesis of a polyisoprenoid essential for both peptidoglycan and WTA synthesis. The work sheds light on mechanisms contributing to the observed suppressive interactions of clomiphene and in turn reveals aspects of the biology that underlie cell wall synthesis in S. aureus. Further, this effort highlights the utility of antagonistic interactions both in high-throughput screening and in compound mode of action studies. Importantly, clomiphene represents a lead for antibacterial drug discovery. PMID- 26283396 TI - Correction for Shin et al., Muscarinic regulation of dopamine and glutamate transmission in the nucleus accumbens. PMID- 26283395 TI - Roles of multiple-proton transfer pathways and proton-coupled electron transfer in the reactivity of the bis-FeIV state of MauG. AB - The high-valent state of the diheme enzyme MauG exhibits charge-resonance (CR) stabilization in which the major species is a bis-Fe(IV) state with one heme present as Fe(IV)=O and the other as Fe(IV) with axial heme ligands provided by His and Tyr side chains. In the absence of its substrate, the high-valent state is relatively stable and returns to the diferric state over several minutes. It is shown that this process occurs in two phases. The first phase is redistribution of the resonance species that support the CR. The second phase is the loss of CR and reduction to the diferric state. Thermodynamic analysis revealed that the rates of the two phases exhibited different temperature dependencies and activation energies of 8.9 and 19.6 kcal/mol. The two phases exhibited kinetic solvent isotope effects of 2.5 and 2.3. Proton inventory plots of each reaction phase exhibited extreme curvature that could not be fit to models for one- or multiple-proton transfers in the transition state. Each did fit well to a model for two alternative pathways for proton transfer, each involving multiple protons. In each case the experimentally determined fractionation factors were consistent with one of the pathways involving tunneling. The percent of the reaction that involved the tunneling pathway differed for the two reaction phases. Using the crystal structure of MauG it was possible to propose proton-transfer pathways consistent with the experimental data using water molecules and amino acid side chains in the distal pocket of the high-spin heme. PMID- 26283397 TI - RIP3-mediated necrotic cell death accelerates systematic inflammation and mortality. AB - Systematic inflammation contributes to the development of many diseases, including cardiovascular disease, which is the leading cause of mortality worldwide. How such inflammation is initiated and maintained throughout the course of disease remains unclear. In the current study, we report the observation of specific phosphorylation of the receptor-interacting protein 3 (RIP3) kinase that marks the activation of programmed necrosis (also called the "necroptosis pathway") in the atherosclerotic plaques in apolipoprotein E (ApoE) knockout mice. The mRNA expression levels of 10 inflammatory cytokines, including IL-1alpha, were decreased significantly in the plaque regions of mice lacking RIP3. Lymphocyte infiltrations in the adipocyte tissue and in skin lesions of ApoE single-knockout mice were significantly mitigated in ApoE/RIP3 double knockout mice. The high percentage of inflammatory monocytes with high levels of lymphocyte antigen 6C in the blood of ApoE single-knockout mice also was greatly decreased in the ApoE/RIP3 double-knockout mice. Most significantly, the double knockout mice displayed dramatically delayed mortality compared with ApoE single knockout mice. Our findings indicate that necrotic death in areas such as atherosclerotic plaques may release cytokines that mobilize monocytes from bone marrow to the lesion sites, exacerbating the lesions in multiple tissues and resulting in the premature death of the animals. PMID- 26283399 TI - Sex determination by multiple sex chromosomes in Xenopus tropicalis. PMID- 26283398 TI - LINE-1 expression and retrotransposition in Barrett's esophagus and esophageal carcinoma. AB - Barrett's esophagus (BE) is a common disease in which the lining of the esophagus transitions from stratified squamous epithelium to metaplastic columnar epithelium that predisposes individuals to developing esophageal adenocarcinoma (EAC). We hypothesized that BE provides a unique environment for increased long interspersed element 1 (LINE-1 or L1) retrotransposition. To this end, we evaluated 5 patients with benign BE, 5 patients with BE and concomitant EAC, and 10 additional patients with EAC to determine L1 activity in this progressive disease. After L1-seq, we confirmed 118 somatic insertions by PCR in 10 of 20 individuals. We observed clonal amplification of several insertions which appeared to originate in normal esophagus (NE) or BE and were later clonally expanded in BE or in EAC. Additionally, we observed evidence of clonality within the EAC cases; specifically, 22 of 25 EAC-only insertions were present identically in distinct regions available from the same tumor, suggesting that these insertions occurred in the founding tumor cell of these lesions. L1 proteins must be expressed for retrotransposition to occur; therefore, we evaluated the expression of open reading frame 1 protein (ORF1p), a protein encoded by L1, in eight of the EAC cases for which formalin-fixed paraffin embedded tissue was available. With immunohistochemistry, we detected ORF1p in all tumors evaluated. Interestingly, we also observed dim ORF1p immunoreactivity in histologically NE of all patients. In summary, our data show that somatic retrotransposition occurs early in many patients with BE and EAC and indicate that early events occurring even in histologically NE cells may be clonally expanded in esophageal adenocarcinogenesis. PMID- 26283400 TI - Confronting and resolving competing values behind conservation objectives. AB - Diverse motivations for preserving nature both inspire and hinder its conservation. Optimal conservation strategies may differ radically depending on the objective. For example, creating nature reserves may prevent extinctions through protecting severely threatened species, whereas incentivizing farmland hedgerows may benefit people through bolstering pest-eating or pollinating species. Win-win interventions that satisfy multiple objectives are alluring, but can also be elusive. To achieve better outcomes, we developed and implemented a practical typology of nature conservation framed around seven common conservation objectives. Using an intensively studied bird assemblage in southern Costa Rica as a case study, we applied the typology in the context of biodiversity's most pervasive threat: habitat conversion. We found that rural habitats in a varied tropical landscape, comprising small farms, villages, forest fragments, and forest reserves, provided biodiversity-driven processes that benefit people, such as pollination, seed dispersal, and pest consumption. However, species valued for their rarity, endemism, and evolutionary distinctness declined in farmland. Conserving tropical forest on farmland increased species that international tourists value, but not species discussed in Costa Rican newspapers. Despite these observed trade-offs, our analyses also revealed promising synergies. For example, we found that maintaining forest cover surrounding farms in our study region would likely enhance most conservation objectives at minimal expense to others. Overall, our typology provides a framework for resolving the competing objectives of modern conservation. PMID- 26283401 TI - Correction to Supporting Information for Merski et al., Homologous ligands accommodated by discrete conformations of a buried cavity. PMID- 26283402 TI - Reply to Chakrabarty et al.: Particles move even in ideal glasses. PMID- 26283403 TI - Vanishing of configurational entropy may not imply an ideal glass transition in randomly pinned liquids. PMID- 26283404 TI - Reply to Lane and Martin: Being and becoming eukaryotes. PMID- 26283405 TI - Eukaryotes really are special, and mitochondria are why. PMID- 26283406 TI - Reply to Luo et al.: Robustness of causal effects of galactic cosmic rays on interannual variation in global temperature. PMID- 26283407 TI - Questionable dynamical evidence for causality between galactic cosmic rays and interannual variation in global temperature. PMID- 26283408 TI - Maternal fatty acid desaturase genotype correlates with infant immune responses at 6 months. AB - Breast milk long-chain PUFA (LCPUFA) have been associated with changes in early life immune responses and may modulate T-cell function in infancy. We studied the effect of maternal fatty acid desaturase (FADS) genotype and breast milk LCPUFA levels on infants' blood T-cell profiles and ex vivo-produced cytokines after anti-CD3/CD28 stimulation of peripheral blood mononuclear cells in 6-month-old infants from the Copenhagen Prospective Study of Asthma in Childhood birth cohort. LCPUFA concentrations of breast milk were assessed at 4 weeks of age, and FADS SNP were determined in both mothers and infants (n 109). In general, breast milk arachidonic acid (AA) levels were inversely correlated with the production of IL-10 (r -0.25; P=0.004), IL-17 (r -0.24; P=0.005), IL-5 (r -0.21; P=0.014) and IL-13 (r -0.17; P=0.047), whereas EPA was positively correlated with the counts of blood regulatory T-cells and cytotoxic T-cells and decreased T-helper cell counts. The minor FADS alleles were associated with lower breast milk AA and EPA, and infants of mothers carrying the minor allele of FADS SNP rs174556 had higher production of IL-10 (r -0.23; P=0.018), IL-17 (r -0.25; P=0.009) and IL-5 (r -0.21; P=0.038) from ex vivo-activated immune cells. We observed no association between T-cell distribution and maternal or infant FADS gene variants. We conclude that increased maternal LCPUFA synthesis and breast milk AA are associated with decreased levels of IL-5, IL-13 (type-2 related), IL-17 (type 17 related) and IL-10 (regulatory immune responses), but not with interferon gamma and TNF-alpha, which could be due to an effect of the maternal FADS variants on the offspring immune response transferred via breast milk LCPUFA. PMID- 26283409 TI - A new strain energy function for modelling ligaments and tendons whose fascicles have a helical arrangement of fibrils. AB - A new strain energy function for the hyperelastic modelling of ligaments and tendons whose fascicles have a helical arrangement of fibrils is derived. The stress-strain response of a single fascicle whose fibrils exhibit varying levels of crimp throughout its radius is calculated and used to determine the form of the strain energy function. The new constitutive law is used to model uniaxial extension test data for human patellar tendon and is shown to provide an excellent fit, with the average relative error being 9.8%. It is then used to model shear and predicts that the stresses required to shear a tendon are much smaller than those required to uniaxially stretch it to the same strain level. Finally, the strain energy function is used to model ligaments and tendons whose fascicles are helical, and the relative effects of the fibril helix angle, the fascicle helix angle and the fibril crimp variable are compared. It is shown that they all have a significant effect; the fibril crimp variable governs the non linearity of the stress-strain curve, whereas the helix angles primarily affect its stiffness. Smaller values of the helix angles lead to stiffer tendons; therefore, the model predicts that one would expect to see fewer helical sub structures in stiff positional tendons, and more in those that are required to be more flexible. PMID- 26283410 TI - Water in hydroxyapatite nanopores: Possible implications for interstitial bone fluid flow. AB - The role of bone water in the activity of this organ is essential in structuring apatite crystals, providing pathways for nutrients and waste involved in the metabolism of bone cells and participating in bone remodelling mechanotransduction. It is commonly accepted that bone presents three levels of porosity, namely the vasculature, the lacuno-canalicular system and the voids of the collagen-apatite matrix. Due to the observation of bound state of water at the latter level, the interstitial nanoscopic flow that may exist within these pores is classically neglected. The aim of this paper is to investigate the possibility to obtain a fluid flow at the nanoscale. That is why a molecular dynamics based analysis of a water-hydroxyapatite system is proposed to analyze the effect of water confinement on transport properties. The main result here is that free water can be observed inside hydroxyapatite pores of a few nanometers. This result would have strong implications in the multiscale treatment of the poromechanical behaviour of bone tissue. In particular, the mechanical properties of the bone matrix may be highly controlled by nanoscopic water diffusion and the classical idea that osteocytic activity is only regulated by bone fluid flow within the lacuno-canalicular system may be discussed again. PMID- 26283411 TI - A kinematic method to detect foot contact during running for all foot strike patterns. AB - The biomechanics of distance running are studied in relation to both understanding injury mechanisms and improving performance. Kinematic methods must be used to identify the stance phase of running when data are recorded during running on a standard treadmill or outside the laboratory. Recently, a focus on foot strike patterns has emerged in the field. Thus, there is a need for a kinematic method to identify foot contact that is equally effective for both rearfoot and non-rearfoot strike patterns. The purpose of this study was to determine whether a new kinematic method could accurately determine foot contact during running in both rearfoot and non-rearfoot strikers. Overground gait data were collected at on 22 runners, 11 with a rearfoot strike pattern and 11 with a non-rearfoot strike pattern. Data were processed to identify foot contact from: vertical ground reaction force, two previously published kinematic methods, and our new kinematic method. Limits of agreement were used to determine bias and random error of each kinematic method compared to ground reaction force onset. The new method had comparable random error at 200 Hz sampling frequency (5 ms per frame) to the previous methods (7 frames vs 6-9 frames) and produced the same offset for both strike patterns (3 frames), while the existing methods had different offsets for different strike patterns (4 or 7 frames). Study findings support use of this new method, as it can be applied to all running strike patterns without adjusting the frame offset, simplifying data processing. PMID- 26283412 TI - Vascular smooth muscle cell functional contractility depends on extracellular mechanical properties. AB - Vascular smooth muscle cells' primary function is to maintain vascular homeostasis through active contraction and relaxation. In diseases such as hypertension and atherosclerosis, this function is inhibited concurrent to changes in the mechanical environment surrounding vascular smooth muscle cells. It is well established that cell function and extracellular mechanics are interconnected; variations in substrate modulus affect cell migration, proliferation, and differentiation. To date, it is unknown how the evolving extracellular mechanical environment of vascular smooth muscle cells affects their contractile function. Here, we have built upon previous vascular muscular thin film technology to develop a variable-modulus vascular muscular thin film that measures vascular tissue functional contractility on substrates with a range of pathological and physiological moduli. Using this modified vascular muscular thin film, we found that vascular smooth muscle cells generated greater stress on substrates with higher moduli compared to substrates with lower moduli. We then measured protein markers typically thought to indicate a contractile phenotype in vascular smooth muscle cells and found that phenotype is unaffected by substrate modulus. These data suggest that mechanical properties of vascular smooth muscle cells' extracellular environment directly influence their functional behavior and do so without inducing phenotype switching. PMID- 26283413 TI - Pressure and shear stress in trabecular bone marrow during whole bone loading. AB - Skeletal adaptation to mechanical loading is controlled by mechanobiological signaling. Osteocytes are highly responsive to applied strains, and are the key mechanosensory cells in bone. However, many cells residing in the marrow also respond to mechanical cues such as hydrostatic pressure and shear stress, and hence could play a role in skeletal adaptation. Trabecular bone encapsulates marrow, forming a poroelastic solid. According to the mechanical theory, deformation of the pores induces motion in the fluid-like marrow, resulting in pressure and velocity gradients. The latter results in shear stress acting between the components of the marrow. To characterize the mechanical environment of trabecular bone marrow in situ, pore pressure within the trabecular compartment of whole porcine femurs was measured with miniature pressure transducers during stress-relaxation and cyclic loading. Pressure gradients ranging from 0.013 to 0.46 kPa/mm were measured during loading. This range was consistent with calculated pressure gradients from continuum scale poroelastic models with the same permeability. Micro-scale computational fluid dynamics models created from computed tomography images were used to calculate the micromechanical stress in the marrow using the measured pressure differentials as boundary conditions. The volume averaged shear stress in the marrow ranged from 1.67 to 24.55 Pa during cyclic loading, which exceeds the mechanostimulatory threshold for mesenchymal lineage cells. Thus, the loading of bone through activities of daily living may be an essential component of bone marrow health and mechanobiology. Additional studies of cell-level interactions during loading in healthy and disease conditions will provide further incite into marrow mechanobiology. PMID- 26283416 TI - Pressure from tobacco industry is delaying vital law in Pakistan, say activists. PMID- 26283414 TI - Venous thromboembolism in the ICU: main characteristics, diagnosis and thromboprophylaxis. AB - Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep venous thrombosis (DVT), is a common and severe complication of critical illness. Although well documented in the general population, the prevalence of PE is less known in the ICU, where it is more difficult to diagnose and to treat. Critically ill patients are at high risk of VTE because they combine both general risk factors together with specific ICU risk factors of VTE, like sedation, immobilization, vasopressors or central venous catheter. Compression ultrasonography and computed tomography (CT) scan are the primary tools to diagnose DVT and PE, respectively, in the ICU. CT scan, as well as transesophageal echography, are good for evaluating the severity of PE. Thromboprophylaxis is needed in all ICU patients, mainly with low molecular weight heparin, such as fragmine, which can be used even in cases of non-severe renal failure. Mechanical thromboprophylaxis has to be used if anticoagulation is not possible. Nevertheless, VTE can occur despite well-conducted thromboprophylaxis. PMID- 26283415 TI - Inhibition of Haemonchus contortus larval development by fungal lectins. AB - BACKGROUND: Lectins are carbohydrate-binding proteins that are involved in fundamental intra- and extracellular biological processes. They occur ubiquitously in nature and are especially abundant in plants and fungi. It has been well established that certain higher fungi produce lectins in their fruiting bodies and/or sclerotia as a part of their natural resistance against free-living fungivorous nematodes and other pests. Despite relatively high diversity of the glycan structures in nature, many of the glycans targeted by fungal lectins are conserved among organisms of the same taxon and sometimes even among different taxa. Such conservation of glycans between free-living and parasitic nematodes is providing us with a useful tool for discovery of novel chemotherapeutic and vaccine targets. In our study, a subset of fungal lectins emanating from toxicity screens on Caenorhabditis elegans was tested for their potential to inhibit larval development of Haemonchus contortus. METHODS: The effect of Coprinopsis cinerea lectins - CCL2, CGL2, CGL3; Aleuria aurantia lectin - AAL; Marasmius oreades agglutinin - MOA; and Laccaria bicolor lectin - Lb-Tec2, on cultivated Haemonchus contortus larval stages was investigated using a larval development test (LDT). To validate the results of the toxicity assay and determine lectin binding capacity to the nematode digestive tract, biotinylated versions of lectins were fed to pre-infective larval stages of H. contortus and visualized by fluorescent microscopy. Lectin histochemistry on fixed adult worms was performed to investigate the presence and localisation of lectin binding sites in the disease-relevant developmental stage. RESULTS: Using an improved larval development test we found that four of the six tested lectins: AAL, CCL2, MOA and CGL2, exhibited a dose-dependent toxicity in LDT, as measured by the number of larvae developing to the L3 stage. In the case of AAL, CGL2 and MOA lectin, doses as low as 5 MUg/ml caused >95 % inhibition of larval development while 40 MUg/ml were needed to achieve the same inhibition by CCL2 lectin. MOA was the only lectin tested that caused larval death while other toxic lectins had larvistatic effect manifesting as L1 growth arrest. Using lectin histochemistry we demonstrate that of all lectins tested, only the four toxic ones displayed binding to the larvae's gut and likewise were found to interact with glycans localized to the gastrodermal tissue of adults. CONCLUSION: The results of our study suggest a correlation between the presence of target glycans of lectins in the digestive tract and the lectin-mediated toxicity in Haemonchus contortus. We demonstrate that binding to the structurally conserved glycan structures found in H. contortus gastrodermal tissue by the set of fungal lectins has detrimental effect on larval development. Some of these glycan structures might represent antigens which are not exposed to the host immune system (hidden antigens) and thus have a potential for vaccine or drug development. Nematotoxic fungal lectins prove to be a useful tool to identify such targets in parasitic nematodes. PMID- 26283417 TI - Editorial: Advance of Interactions Between Exogenous Natural Bioactive Peptides and Intestinal Barrier and Immune Responses. PMID- 26283418 TI - Seasonality in malaria transmission: implications for case-management with long acting artemisinin combination therapy in sub-Saharan Africa. AB - BACKGROUND: Long-acting artemisinin-based combination therapy (LACT) offers the potential to prevent recurrent malaria attacks in highly exposed children. However, it is not clear where this advantage will be most important, and deployment of these drugs is not rationalized on this basis. METHODS: To understand where post-treatment prophylaxis would be most beneficial, the relationship between seasonality, transmission intensity and the interval between malaria episodes was explored using data from six cohort studies in West Africa and an individual-based malaria transmission model. The total number of recurrent malaria cases per 1000 child-years at risk, and the fraction of the total annual burden that this represents were estimated for sub-Saharan Africa. RESULTS: In settings where prevalence is less than 10 %, repeat malaria episodes constitute a small fraction of the total burden, and few repeat episodes occur within the window of protection provided by currently available drugs. However, in higher transmission settings, and particularly in high transmission settings with highly seasonal transmission, repeat malaria becomes increasingly important, with up to 20 % of the total clinical burden in children estimated to be due to repeat episodes within 4 weeks of a prior attack. CONCLUSION: At a given level of transmission intensity and annual incidence, the concentration of repeat malaria episodes in time, and consequently the protection from LACT is highest in the most seasonal areas. As a result, the degree of seasonality, in addition to the overall intensity of transmission, should be considered by policy makers when deciding between ACT that differ in their duration of post-treatment prophylaxis. PMID- 26283419 TI - BEACON: automated tool for Bacterial GEnome Annotation ComparisON. AB - BACKGROUND: Genome annotation is one way of summarizing the existing knowledge about genomic characteristics of an organism. There has been an increased interest during the last several decades in computer-based structural and functional genome annotation. Many methods for this purpose have been developed for eukaryotes and prokaryotes. Our study focuses on comparison of functional annotations of prokaryotic genomes. To the best of our knowledge there is no fully automated system for detailed comparison of functional genome annotations generated by different annotation methods (AMs). RESULTS: The presence of many AMs and development of new ones introduce needs to: a/ compare different annotations for a single genome, and b/ generate annotation by combining individual ones. To address these issues we developed an Automated Tool for Bacterial GEnome Annotation ComparisON (BEACON) that benefits both AM developers and annotation analysers. BEACON provides detailed comparison of gene function annotations of prokaryotic genomes obtained by different AMs and generates extended annotations through combination of individual ones. For the illustration of BEACON's utility, we provide a comparison analysis of multiple different annotations generated for four genomes and show on these examples that the extended annotation can increase the number of genes annotated by putative functions up to 27%, while the number of genes without any function assignment is reduced. CONCLUSIONS: We developed BEACON, a fast tool for an automated and a systematic comparison of different annotations of single genomes. The extended annotation assigns putative functions to many genes with unknown functions. BEACON is available under GNU General Public License version 3.0 and is accessible at: http://www.cbrc.kaust.edu.sa/BEACON/ . PMID- 26283420 TI - Is 'mainstreaming AYUSH' the right policy for Meghalaya, northeast India? AB - BACKGROUND: National policy on medical pluralism in India encourages the mainstreaming of AYUSH (Ayurveda, Yoga, Unani, Siddha, and Homeopathy) systems and the revitalization of local health traditions (LHT). In Meghalaya state in the northeast, the main LHT is its indigenous tribal traditional medicine. This paper presents the perceptions of tribal medicine and of AYUSH systems among various policy actors and locates the tribal medicine of Meghalaya within the policy on medical pluralism currently being implemented in the state, a region that is ethnically and culturally different and predominantly inhabited by indigenous peoples. METHODS: A stakeholder mapping exercise identified appropriate policy actors and 46 in-depth interviews were conducted with policy makers, doctors, academics, members of healer associations and elders of the community. A further 44 interviews were conducted with 24 Khasi and 20 Garo traditional healers. Interview data were supplemented with document analysis and observations. Qualitative data were analyzed using thematic content analysis that incorporated elements of grounded theory. RESULTS: In Meghalaya there is high awareness and utilization of tribal medicine, but no visible efforts by the public sector to support or engage with healers. The AYUSH systems in contrast had little local acceptance but promotion of these systems has led to a substantial increase in AYUSH doctors, particularly homeopaths, in rural areas. Policy actors outside the health department saw an important role for tribal medicine due to its popularity, local belief in its efficacy and its cultural resonance. The need to engage with healers to enhance referral, training, documentation and research of tribal medicine was made. CONCLUSIONS: The wide acceptance of tribal medicine suggests that tribal medicine needs to be supported. The results of the study question the process of the implementation of the 'mainstreaming AYUSH' policy for Meghalaya and highlight the importance of contextualizing health policy within the local culture. A potential role for Health Policy and Systems Research (HPSR) at sub-national levels is also highlighted. PMID- 26283421 TI - CD4(+)CD25(-)Foxp3(+) T cells play a role in tuberculous hydrothorax rather than malignant hydrothorax. AB - BACKGROUND: Foxp3(+) T cells regulate inflammation and tumorigenesis. However, little is known about the role of different subsets of Foxp3(+) T cells in malignant or tuberculous hydrothorax. METHODS: The numbers of CD4(+)CD25(+)Foxp3(+), CD4(+)CD25(-)Foxp3(+) T cells and the levels of some inflammatory cytokines in patients with tuberculous hydrothorax, malignant hydrothorax, and healthy controls (HCs) were examined by flow cytometry and ELISA. The potential association between the numbers of different subsets of Foxp3 + T cells and the values of clinical measures were analyzed. RESULTS: The numbers of peripheral blood CD4(+)CD25(+)Foxp3(+) T cells were greater in malignant hydrothorax patients than in HCs, but fewer than those of hydrothorax in patients. The percentages of circulating IL-10(+) or LAP(+) CD4(+)CD25(+)Foxp3(+) T cells were higher than in the hydrothorax in patients with malignant hydrothorax. The numbers of circulating CD4(+)CD25(-)Foxp3(+) T cells were significantly fewer in patients with tuberculous hydrothorax than in HCs, and both the numbers of circulating CD4(+)CD25(+)Foxp3(+) and CD4(+)CD25( )Foxp3(+) T cells were significantly fewer than in the hydrothorax in patients. Significantly higher percentages of circulating IL-10(+) or LAP(+) CD4(+)CD25(+)Foxp3(+) and CD4(+)CD25(-)Foxp3(+) T cells were detected in tuberculous hydrothorax patients. The numbers of CD4(+)CD25(+)Foxp3(+) and CD4(+)CD25(-)Foxp3(+) T cells were associated with hydrothorax adenosine deaminase (ADA) levels in tuberculous hydrothorax patients, while CD4(+)CD25(+)Foxp3(+) T cells were associated with carcino-embryonic antigen (CEA) in malignant hydrothorax patients. The concentrations of serum IL-6 and TGF beta in the patients were significantly higher than that in the HCs, but lower than that in the corresponding hydrothorax. A similar pattern of IL-10 was observed in different groups, except that there was no significant difference in the levels of serum IL-10 between the tuberculous hydrothorax patients and HCs. CONCLUSIONS: CD4(+)CD25(-)Foxp3(+) T cells, which have lower inhibitory function than CD4(+)CD25(+)Foxp3(+) T cells, may play a role in tuberculous hydrothorax. PMID- 26283422 TI - [Persistent reaction to minoxidil skin patch testing mimicking pseudolymphoma]. PMID- 26283423 TI - [Generalised contact eczema: Care is needed in selecting a lubricant for digital rectal examination]. PMID- 26283424 TI - [Incidence of skin and non-skin cancers in Afro-Caribbean renal transplant recipients: Guadeloupe data from 2004 to 2011]. AB - BACKGROUND: Cancer is the main complication of transplantation surgery. The literature concerning renal transplant recipients among the Afro-Caribbean population is scant. The aim of this study was to determine the incidence of cancer in these patients, with the secondary objective being to identify predisposing factors for cancer. PATIENTS AND METHODS: This was an epidemiological and retrospective study that included all Guadeloupians of phototype V-VI undergoing renal transplantation from 01/01/2004 to 31/12/2011. Skin cancer screening was performed before transplantation and during an annual dermatological consultation following transplantation. Screening for non cutaneous cancers was guided by clinical symptoms or by the results of the screening examinations recommended in the current guidelines. At the study time point (31/12/2011), all patients were examined by a dermatologist. RESULTS: One hundred and two patients were included : 42 women and 60 men (mean age: 52.1+/ 11.6 years at transplantation). Eight cancers were diagnosed. The cumulative incidence of cancer was 7.8% at 3 years. Three factors were associated with more rapid onset of cancer: personal history or familial history of cancer, and genital lesion induced by HPV. CONCLUSION: Our results suggest a low incidence of cancer in Afro-Caribbean renal transplant patients. Personal or family history of cancer and HPV-induced genital lesions would appear to accelerate the onset of cancer in this population. PMID- 26283425 TI - Neuronal Nitric Oxide Synthase (nNOS, NOS1) rs693534 and rs7977109 Variants and Risk for Migraine. AB - BACKGROUND/OBJECTIVES: Many biochemical, pharmacological, neuropathological, and experimental data suggest a possible role of nitric oxide in the pathogenesis of migraine. We investigated the possible association between functional single nucleotide polymorphisms (SNPs) in the neuronal nitric oxide synthase gene (NOS1 or nNOS; chromosome 12q24.22) and the risk for migraine. METHODS: We studied the frequency of the of rs7977109 and rs693534 genotypes and allelic variants in 197 patients with migraine and 308 healthy controls using a TaqMan-based qPCR assay. As a secondary analysis, we studied the possible influence of gender, age at onset of migraine, positive family history of migraine, and presence or absence of aura on the genotypes frequency. RESULTS: The frequencies of rs7977109 and rs693534 genotypes and allelic variants were not associated with the risk for migraine with OR for minor alleles = 0.94 (95% CI 0.72-1.23) and = 0.88 (0.68 1.15), respectively, and the lack of association was not influenced by gender, age at onset of migraine, positive family history of migraine, and presence or absence of aura. CONCLUSION: NOS1 rs7977109 and rs693534 genotypes and allelic variants are not associated with the risk for migraine in Caucasian Spanish people. PMID- 26283427 TI - Kirkwood-Buff Integrals for Finite Volumes. AB - Exact expressions for finite-volume Kirkwood-Buff (KB) integrals are derived for hyperspheres in one, two, and three dimensions. These integrals scale linearly with inverse system size. From this, accurate estimates of KB integrals for infinite systems are obtained, and it is shown that they converge much better than the traditional expressions. We show that this approach is very suitable for the computation of KB integrals from molecular dynamics simulations, as we obtain KB integrals for open systems by simulating closed systems. PMID- 26283426 TI - Interaction between TRPA1 and TRPV1: Synergy on pulmonary sensory nerves. AB - Transient receptor potential ankyrin type 1 (TRPA1) and vanilloid type 1 (TRPV1) receptors are co-expressed in vagal pulmonary C-fiber sensory nerves. Because both these ligand-gated non-selective cation channels are sensitive to a number of endogenous inflammatory mediators, it is highly probable that they can be activated simultaneously during airway inflammation. Studies were carried out to investigate whether there is an interaction between these two polymodal transducers upon simultaneous activation, and how it modulates the activity of vagal pulmonary C-fiber sensory nerves. Our studies showed a distinct potentiating effect induced abruptly by simultaneous activations of TRPA1 and TRPV1 by their respective selective agonists, allyl isothiocyanate (AITC) and capsaicin (Cap), at near-threshold concentrations. This synergistic effect was demonstrated in the studies of single-unit recording of vagal bronchopulmonary C fiber afferents and the reflex responses elicited by activation of these afferents in intact animals, as well as in the isolated nodose and jugular bronchopulmonary sensory neurons. This potentiating effect was absent when either AITC or Cap was replaced by non-TRPA1 and non-TRPV1 chemical activators of these neurons, demonstrating the selectivity of the interaction between these two TRP channels. Furthermore, the synergism was dependent upon the extracellular Ca(2+), and the rapid onset of the action further suggests that the interaction probably occurred locally at the sites of these channels. These findings suggest that the TRPA1-TRPV1 interaction may play an important role in regulating the function and excitability of pulmonary sensory neurons during airway inflammation, but the mechanism underlying this positive interaction is not yet fully understood. PMID- 26283429 TI - Interfacial Structure of Room-Temperature Ionic Liquids at the Solid-Liquid Interface as Probed by Sum Frequency Generation Spectroscopy. AB - Fundamental and basic information about molecules at the solid-liquid interface is limited primarily because most spectroscopic methods are not able to specifically detect the surface buried between two condensed phases. The second order nonlinear techniques sum frequency generation (SFG) is able to probe the noncentrosymmetric environment between two bulk phases and has been used in many surface studies. In this Perspective, the use of SFG in studies of ionic liquids at the solid-liquid interface will be discussed. Several interfaces are discussed including dielectrics, semiconductors, and metal. SFG results suggest a specific surface model that the ionic liquid structure persists approximately one layer into the bulk liquid and that this is mostly due to the charge neutralization at the surface. PMID- 26283428 TI - Hidden Properties of Carbon Dots Revealed After HPLC Fractionation. AB - Carbon dots (C-dots) are often synthesized, modified, and studied as a mixture. Unfortunately, the spectroscopic and biological properties measured for such C dots assume that there is a high degree of homogeneity in the produced sample. By means of high-resolution separation techniques, we show that "as-synthesized" C dots exist as a relatively complex mixture and that an unprecedented reduction in such complexity can reveal fractions of C-dots with unique luminescence properties. The wavelength-dependent photoluminescence commonly assigned as an inherent property of C-dots is not present in fractionated samples. While ultraviolet-visible absorption profiles reported for C-dots are typically featureless, we have found fractions of C-dots possessing unique absorption bands, with different fractions possessing specific emission wavelengths. Furthermore, fractionated C-dots showed profound differences in emission quantum yield, allowing for brighter C-dots to be isolated from an apparent low quantum yield mixture. These more luminescent fractions of C-dots displayed improved biological compatibility and usefulness as cellular imaging probes. PMID- 26283430 TI - Combined Self-Consistent-Field and Spin-Flip Tamm-Dancoff Density Functional Approach to Potential Energy Surfaces for Photochemistry. AB - We present a new approach to calculating potential energy surfaces for photochemical reactions by combining self-consistent-field calculations for single-reference ground and excited states with symmetry-corrected spin-flip Tamm Dancoff approximation calculations for multireference electronic states. The method is illustrated by an application with the M05-2X exchange-correlation functional to cis-trans isomerization of the penta-2,4-dieniminium cation, which is a model (with three conjugated double bonds) of the protonated Schiff base of retinal. We find good agreement with multireference configuration interaction plus-quadruples (MRCISD+Q) wave function calculations along three key paths in the strong-interaction region of the ground and first excited singlet states. PMID- 26283431 TI - Patterning Graphitic C-N Sheets into a Kagome Lattice for Magnetic Materials. AB - We propose porous C-N-based structures for biocompatible magnetic materials that do not contain even a single metal ion. Using first-principles calculations based on density functional theory, we show that when patterned in the form of a kagome lattice, nonmagnetic g-C3N4 not only becomes ferromagnetic but also its magnetic properties can be further enhanced by applying external strain. Similarly, the magnetic moment per atom in ferromagnetic g-C4N3 is increased three fold when patterned into a kagome lattice. The Curie temperature of g-C3N4 kagome lattice is 100 K, while that of g-C4N3 kagome lattice is much higher, namely, 520 K. To date, all of the synthesized two- and three-dimensional magnetic kagome structures contain metal ions and are toxic. The objective of our work is to stimulate an experimental effort to develop nanopatterning techniques for the synthesis of g-C3N4- and g-C4N3-based kagome lattices. PMID- 26283432 TI - Simulating Supercapacitors: Can We Model Electrodes As Constant Charge Surfaces? AB - Supercapacitors based on an ionic liquid electrolyte and graphite or nanoporous carbon electrodes are simulated using molecular dynamics. We compare a simplified electrode model in which a constant, uniform charge is assigned to each carbon atom with a realistic model in which a constant potential is applied between the electrodes (the carbon charges are allowed to fluctuate). We show that the simulations performed with the simplified model do not provide a correct description of the properties of the system. First, the structure of the adsorbed electrolyte is partly modified. Second, dramatic differences are observed for the dynamics of the system during transient regimes. In particular, upon application of a constant applied potential difference, the increase in the temperature, due to the Joule effect, associated with the creation of an electric current across the cell follows Ohm's law, while unphysically high temperatures are rapidly observed when constant charges are assigned to each carbon atom. PMID- 26283433 TI - XH/pi (X = C, Si) Interactions in Graphene and Silicene: Weak in Strength, Strong in Tuning Band Structures. AB - The lack of a band gap has greatly hindered the applications of graphene in electronic devices. By means of dispersion-corrected density functional theory computations, we demonstrated that considerable CH/pi interactions exist between graphene and its fully (graphane) or patterned partially (C4H) hydrogenated derivatives. Due to the equivalence breaking of two sublattices of graphene, a 90 meV band gap is opened in the graphene/C4H bilayer. The band gap can be further increased to 270 meV by sandwiching graphene between two C4H layers. By taking advantage of the similar SiH/pi interactions, a 120 meV band gap also can be opened for silicene. Interestingly, the high carrier mobility of graphene/silicene can be well-preserved. Our theoretical results suggest a rather practical solution for gap opening of graphene and silicene, which would allow them to serve as field effect transistors and other nanodevices. PMID- 26283434 TI - Implications of CO2 Contamination in Rechargeable Nonaqueous Li-O2 Batteries. AB - In this Letter, the effect of CO2 contamination on nonaqueous Li-O2 battery rechargeability is explored. Although CO2 contamination was found to increase the cell's discharge capacity, it also spontaneously reacts with Li2O2 (the primary discharge product of a nonaqueous Li-O2 battery) to form Li2CO3. CO2 evolution from Li2CO3 during battery charging was found to occur only at very high potentials (>4 V) compared to O2 evolution from Li2O2 (~3-3.5 V), and as a result, the presence of CO2 during discharge dramatically reduced the voltaic efficiency of the discharge-charge cycle. These results emphasize the importance of not only completely removing CO2 from air fed to a Li-air battery, but also developing stable cathodes and electrolytes that will not decompose during battery operation to form carbonate deposits. PMID- 26283435 TI - Hole Transfer from Low Band Gap Quantum Dots to Conjugated Polymers in Organic/Inorganic Hybrid Photovoltaics. AB - We use photoinduced absorption (PIA) spectroscopy to investigate pathways for photocurrent generation in hybrid organic/inorganic quantum dot bulk heterojunction solar cells. We study blends of the conjugated polymer poly(2,3 bis(2-(hexyldecyl)quinoxaline-5,8-diyl-alt-N-(2-hexyldecyl)dithieno[3,2-b:2',3' d]pyrrole) (PDTPQx-HD) with PbS quantum dots and find that positively charged polarons are formed on the conjugated polymer following selective photoexcitation of the PbS quantum dots. This result provides a direct spectroscopic fingerprint demonstrating that photoinduced hole transfer occurs from the photoexcited quantum dots to the host polymer. We compute the relative yields of long-lived holes following photoexcitation of both the polymer and quantum dot phases and estimate that more long-lived polarons are produced per photon absorbed by the polymer phase than by the quantum dot phase. PMID- 26283436 TI - Catalysts Transform While Molecules React: An Atomic-Scale View. AB - We explore how the atomic-scale structural and chemical properties of an oxide supported monolayer (ML) catalyst are related to catalytic behavior. This case study is for vanadium oxide deposited on a rutile alpha-TiO2(110) single-crystal surface by atomic layer deposition (ALD) undergoing a redox reaction cycle in the oxidative dehydrogenation (ODH) of cyclohexane. For measurements that require a greater effective surface area, we include a comparative set of ALD-processed rutile powder samples. In situ single-crystal X-ray standing wave (XSW) analysis shows a reversible vanadium oxide structural change through the redox cycle. Ex situ X-ray photoelectron spectroscopy (XPS) shows that V cations are 5+ in the oxidized state and primarily 4+ in the reduced state for both the (110) single crystal surface and the multifaceted surfaces of the powder sample. In situ diffuse reflectance infrared Fourier transform spectroscopy, which could only achieve a measurable signal level from the powder sample, indicates that these structural and chemical state changes are associated with the change of the V?O vanadyl group. Catalytic tests on the powder-supported VOx revealed benzene as the major product. This study not only provides atomic-scale models for cyclohexane molecules interacting with V sites on the rutile surface but also demonstrates a general strategy for linking the processing, structure, properties, and performance of oxide-supported catalysts. PMID- 26283437 TI - Capturing Ultrafast Quantum Dynamics with Femtosecond and Attosecond X-ray Core Level Absorption Spectroscopy. AB - Recent technical advances in ultrafast laser sources enable the generation of femtosecond and attosecond soft X-ray pulses in tabletop laser setups as well as accelerator-based synchrotron and free-electron laser sources. These new light sources can be harnessed via pump-probe spectroscopy to elucidate ultrafast quantum dynamics in atoms, molecules, and condensed matter with unprecedented time resolution and chemical sensitivity. Employing such ultrashort pulses in transient X-ray absorption spectroscopy combines the unique advantages of core level absorption probing of chemical environments and oxidation states with the ability to obtain ultimately freeze-frame snapshots of electronic and nuclear dynamics. In this Perspective, we provide an overview of the progress in applying the recently developed technique of femtosecond to attosecond time-resolved soft X-ray transient absorption spectroscopy to the study of ultrafast phenomena, including some of our own efforts to elucidate the interaction of intense laser pulses with atoms and molecules in the strong-field, nonperturbative limit. Possible avenues for future work are outlined. PMID- 26283438 TI - Interrogating Interfaces and Core Electrons via Nonlinear Laser Methods. PMID- 26283439 TI - Amplitude of Relaxations in Fluorescence Correlation Spectroscopy for Fluorophores That Diffuse Together. AB - The amplitude of chemical relaxations in fluorescence correlation spectroscopy (FCS) is an important parameter that directly relates to not only the equilibrium constant of the relaxations but also the number of individual fluorophores that diffuse together. In this Letter we answer the question how exactly the amplitude of the relaxations in FCS changes with respect to the number of identical fluorophores on one cargo. We anchored tetramethylrhodamine molecules onto each arm of a DNA Holliday junction molecule so that the codiffusing dyes were capable of performing independent fluorescent fluctuations. We found that the amplitudes of the relaxations were inversely proportional to the number of the dyes on each cargo molecule, well agreeing with the theoretical prediction derived in this Letter. The result provides a guideline for the FCS data analysis and points out a simple way to determine the number of molecules that a cargo carries. PMID- 26283440 TI - Enhanced Magnetic Anisotropy via Quasi-Molecular Magnet at Organic-Ferromagnetic Contact. AB - To realize the origin of efficient spin injection at organic-ferromagnetic contact in organic spintronics, we have implemented the formation of quasi molecular magnet via surface restructuring of a strong organic acceptor, tetrafluoro-tetracyano-quinodimethane (F4-TCNQ), in contact with ferromagnetic cobalt. Our results demonstrate a spin-polarized F4-TCNQ layer and a remarkably enhanced magnetic anisotropy of the Co film. The novel magnetic properties are contributed from strong magnetic coupling caused by the molecular restructuring that displays an angular anchoring conformation of CN and upwardly protruding fluorine atoms. We conclude that the pi bonds of CN, instead of the lone-pair electrons of N atoms, contribute to the hybridization-induced magnetic coupling between CN and Co and generate a superior magnetic order on the surface. PMID- 26283441 TI - Multiexciton Generation in IV-VI Nanocrystals: The Role of Carrier Effective Mass, Band Mixing, and Phonon Emission. AB - We study the role of the effective mass, band mixing, and phonon emission on multiexciton generation in IV-VI nanocrystals. A four-band k . p effective mass model, which allows for an independent variation of these parameters, is adopted to describe the electronic structure of the nanocrystals. Multiexciton generation efficiencies are calculated using a Green's function formalism, providing results that are numerically similar to impact excitation. We find that multiexciton generation efficiencies are maximized when the effective mass of the electron and hole are small and similar. Contact with recent experimental results for multiexciton generation in PbS and PbSe is made. PMID- 26283442 TI - Vibrational Enhancement Factor of the Cl + CHD3(v1 = 1) Reaction: Rotational Probe Effects. AB - The vibrational enhancement factor in the Cl + CHD3(v1 = 1) reaction is revisited over the collisional energy range of 2-5.9 kcal mol(-1). Contrary to the previous results obtained by probing the low-|N, K? states of CD3(v = 0) products, CH stretching excitation becomes more efficacious than the same amount of translational energy in promoting the HCl(v) + CD3(v = 0) product pairs when all |N, K? states are probed. Whereas the new vibrational enhancement factors, which are three to four times larger than the previous report, agree reasonably well with a recent reduced-dimensionality quantum dynamics calculation, a cautious note is made on the different initial |J,K? rotational selections of the CHD3 reactants in the present theory-experiment comparison. PMID- 26283443 TI - Fast Low-Spin Cobalt Complex Redox Shuttles for Dye-Sensitized Solar Cells. AB - A low-spin cobalt(II) complex, cobalt bis(trithiacyclononane), [Co(ttcn)2](3+/2+), was investigated for use as a redox shuttle in dye-sensitized solar cells, DSSCs. This unique cobalt complex redox shuttle is stable, transparent, and easy to synthesize from commercial ligands and has attractive energetic and kinetic features for use in DSSCs. Initial results indicate that the overall performance is limited by recombination. Variation of the sensitizer and deposition of an ultrathin coating of alumina on nanoparticle-based TiO2 DSSC photoanodes reduced recombination, which resulted in significantly improved quantum yields. The photovoltaic behavior was compared to the current record efficiency cobalt tris-bipyridine, [Co(bpy)3](3+/2+), redox shuttle and produced similar results. Further use of high extinction organic sensitizers with only ~200 mV of driving force for regeneration was examined, which produced efficiencies of over 2%; importantly, regeneration is not rate-limiting in this system, thus demonstrating the promise of using such fast redox shuttles. PMID- 26283444 TI - Neutral and Charged Oxygen Vacancies Induce Two-Dimensional Electron Gas Near SiO2/BaTiO3 Interfaces. AB - An atomistic model of the SiO2/BaTiO3 interface was constructed using ab initio molecular dynamics. Analysis of its structure and electronic properties reveals that (i) the band gap at the stoichiometric SiO2/BaTiO3 interface is significantly smaller than those of the bulk BaTiO3 and SiO2, and (ii) the interface contains ~5.5 nm(-2) oxygen vacancies (V(2+)) in the outermost TiO2 plane of the BaTiO3 and ~11 nm(-2) Si-O-Ti bonds resulting from breaking Si-O-Si and Ti-O-Ti bonds and subsequent rearrangement of the atoms. This structure gives rise to the interface polar region with positive and negative charges localized in the BaTiO3 and SiO2 parts of the interface, respectively. We propose that high dielectric response, observed experimentally in the SiO2-coated nanoparticles of BaTiO3, is due to the electron gas formed in oxygen-deficient BaTiO3 and localized in the vicinity of the polar interface. PMID- 26283445 TI - Electron at the Surface of Water: Dehydrated or Not? AB - The hydrated electron is a crucial species in radiative processes, and it has been speculated that its behavior at the water surface could lead to specific interfacial chemical properties. Here, we address fundamental questions concerning the structure and energetics of an electron at the surface of water. We use the method of ab initio molecular dynamics, which was shown to provide a faithful description of solvated electrons in large water clusters and in bulk water. The present results clearly demonstrate that the surface electron is mostly buried in the interfacial water layer, with only about 10 % of its density protruding into the vapor phase. Consequently, it has a structure that is very similar to that of an electron solvated in the aqueous bulk. This points to a general feature of charges at the surface of water, namely, that they do not behave as half-dehydrated but rather as almost fully hydrated species. PMID- 26283446 TI - Longitudinal Andhra Pradesh Eye Disease Study: rationale, study design and research methodology. AB - BACKGROUND: The rationale, objectives, study design and procedures for the longitudinal Andhra Pradesh Eye Disease Study are described. DESIGN: A longitudinal cohort study was carried out. PARTICIPANTS: Participants include surviving cohort from the rural component of Andhra Pradesh Eye Disease Study. METHODS: During 1996-2000, Andhra Pradesh Eye Disease Survey was conducted in three rural (n = 7771) and one urban (n = 2522) areas (now called Andhra Pradesh Eye Disease Study 1). In 2009-2010, a feasibility exercise (Andhra Pradesh Eye Disease Study 2) for a longitudinal study (Andhra Pradesh Eye Disease Study 3) was undertaken in the rural clusters only, as urban clusters no longer existed. In Andhra Pradesh Eye Disease Study 3, a detailed interview will be carried out to collect data on sociodemographic factors, ocular and systemic history, risk factors, visual function, knowledge of eye diseases and barriers to accessing services. All participants will also undergo a comprehensive eye examination including photography of lens, optic disc and retina, Optic Coherence Tomography of the posterior segment, anthropometry, blood pressure and frailty measures. MAIN OUTCOME MEASURES: Measures include estimates of the incidence of visual impairment and age-related eye disease (lens opacities, glaucoma and age-related macular degeneration) and the progression of eye disease (lens opacities and myopia) and associated risk factors. RESULTS: Of the 7771 respondents examined in rural areas in Andhra Pradesh Eye Disease Study 1, 5447 (70.1%) participants were traced in Andhra Pradesh Eye Disease Study 2. These participants will be re examined. CONCLUSIONS: Andhra Pradesh Eye Disease Study 3 will provide data on the incidence and progression of visual impairment and major eye diseases and their associated risk factors in India. The study will provide further evidence to aid planning eye care services. PMID- 26283447 TI - Effect of feeding on the pharmacokinetics of oral minocycline in healthy research dogs. AB - BACKGROUND: The effect of food on minocycline oral absorption in dogs is unknown. OBJECTIVE: The objective was to determine the pharmacokinetics of minocycline after administration of a single oral dose in fed and fasted dogs. METHODS: Ten research hounds were administered oral minocycline (approximately 5 mg/kg) with and without food, in a crossover study, with a one-week wash-out between treatments. Blood samples were collected immediately prior to minocycline administration and over 24 h. Minocycline plasma drug concentrations were measured using high-performance liquid chromatography using ultraviolet detection and were analysed with compartmental modelling to determine primary pharmacokinetic parameters. Each dog was analysed independently, followed by calculation of means and variation of the dogs. The Wilcoxon signed-rank test [analysing secondary pharmacokinetic parameters - peak concentration (CMAX ), area under the concentration versus time curve (AUC)] was used to compare the two groups. A population pharmacokinetic modelling approach was performed using nonlinear mixed effects modelling of primary parameters for the population as fixed effects and the difference between subjects as a random effect. Covariate analysis was used to identify the source of variability in the population. RESULTS: No significant difference was found between treatments for AUC (P = 0.0645), although AUC was higher in fasted dogs. A significant difference was found for CMAX (P = 0.0059), with fasted dogs attaining a higher CMAX . The covariate of fed versus fasted accounted for a significant variation in the pharmacokinetics. CONCLUSIONS AND CLINICAL IMPORTANCE: Because feeding was a significant source of variation for the population's primary pharmacokinetic parameters and fasted dogs had higher minocycline concentrations, we recommend administering minocycline without food. PMID- 26283448 TI - Case of erythrokeratodermia variabilis successfully treated with oral vitamin A. PMID- 26283449 TI - Substantial Improvement of Short Wavelength Response in n-SiNW/PEDOT:PSS Solar Cell. AB - We report herein on the effects of silicon nanowire with different morphology on the device performance of n-SiNW/PEDOT:PSS hybrid solar cells. The power conversion efficiency (PCE) and external quantum efficiency (EQE) of the SiNW/PEDOT:PSS hybrid solar cells can be optimized by varying the length of the silicon nanowires. The optimal length of silicon nanowires is 0.23 MUm, and the hybrid solar cell with the optimal length has the V oc of 569 mV, J sc of 30.1 mA/cm(2), and PCE of 9.3 %. We fabricated more isolated silicon nanowires with the diluted etching solution. And the J sc of the hybrid solar cell with more isolated nanowires has a significant enhancement, from 30.1 to 33.2 mA/cm(2). The remarkable EQE in the wavelength region of 300 and 600 nm was also obtained, which are in excess of 80 %. Our work provides a simple method to substantially improve the EQE of hybrid solar cell in the short wavelength region. PMID- 26283450 TI - Bi-Assisted CdTe/CdS Hierarchical Nanostructure Growth for Photoconductive Applications. AB - We developed a method to control the structure of CdTe nanowires by adopting Bi mixed CdTe powder source to a catalyst-assisted chemical vapor deposition, which allowed us to fabricate CdTe/CdS hierarchical nanostructures. We demonstrated that diverse nanostructures can be grown depending on the combination of the Bi powder and film catalysts. As a proof of concepts, we grew CdTe/CdS branched nanowires for the fabrication of photodetectors. The hierarchical nanostructure based photodetectors showed an improved photoresponsivity compared to the single CdTe nanowire (NW)-based photodetector. Our strategy can be a simple but powerful method for the development of advanced optoelectronic devices and other practical applications. PMID- 26283451 TI - Should we also evaluate SET together with CIP2A for the treatment with second generation tyrosine kinase inhibitors in chronic myeloid leukemia? PMID- 26283452 TI - Effects of different formulations of alpha-tocopherol acetate (vitamin E) on growth performance, meat quality and antioxidant capacity in broiler chickens. AB - The objective of this study was to investigate and compare the effects of alpha tocopherol acetate (vitamin E (VE)) and microencapsulated VE (MVE) on growth performance, meat quality and antioxidant capacity in broiler chickens. A total of 360 d-old broiler chicks were procured and randomly allocated into three groups with 6 replicates. Each replicate had 20 chickens. Chickens were fed with basal diets (CON group) or experimental diets supplemented with 20 mg/kg VE (VE group) or 20 mg/kg MVE (MVE group) for 42 d. The results showed that the MVE group had higher body weight gain (BWG) than the CON and VE groups, and higher gain/feed ratio (G/F ratio) than the CON group during the period of 22-42 d. During the whole experiment, a higher increase in BWG was found in the MVE group than the CON group. Chickens fed on diets supplemented with the VE or MVE had lower abdominal fat percentage, higher pH and antioxidant enzyme activity than the CON group in the breast meat. There was an increased tendency in the hepatic glutathione peroxidase (GSH-Px) enzyme activity of the VE and MVE groups than the CON group. The hepatic mitochondrial total antioxidant capacity and GSH-Px enzyme activity in the MVE group were higher than the CON group. Hepatic 2,2-dipheny-L picrylhydrazyl scavenging activity of the MVE group was higher than the CON group. These results suggested that the dietary addition of VE or MVE could improve breast meat quality in broilers. MVE supplementation may improve growth performance, hepatic mitochondrial antioxidant capacity and free radical scavenging capacity in chickens. In addition, dietary supplementation of MVE gave better broiler growth performance than VE. PMID- 26283453 TI - Reply: To PMID 25813012. PMID- 26283454 TI - Prognosis after maternal placental events and revascularization: PAMPER study. AB - BACKGROUND: Middle-aged women are at higher risk than men of death after coronary artery revascularization. Maternal placental syndromes (gestational hypertension, preeclampsia, placental abruption, and placental infarction) are associated with premature coronary artery disease, but their influence on survival after coronary artery revascularization is unknown. OBJECTIVE: The purpose of this study was to determine whether a history of maternal placental syndromes alters the risk of death after coronary artery revascularization in middle-aged women. STUDY DESIGN: We completed a population-based retrospective cohort study among all hospitals in Ontario, Canada, where universal health care includes all aspects of antenatal and delivery care as well as all outpatient and inpatient health care, which includes coronary revascularization. We included 1985 middle-aged women who underwent a first percutaneous coronary intervention or coronary artery bypass grafting between 1993 and 2012 and who had >=1 previous delivery. We excluded those with cardiovascular disease <=1 year before or coronary revascularization <=90 days after any delivery. The main study outcome, determined a priori, was all-cause death. Hazard ratios were adjusted for age, socioeconomic status, parity, revascularization type, time since last delivery, hypertension, diabetes mellitus, obesity, dyslipidemia, tobacco or drug dependence, and kidney disease. RESULTS: Three hundred sixty-two of 1985 women (18.2%) who underwent coronary artery revascularization had a previous maternal placental syndrome event. The mean age at index coronary revascularization was 45 years; percutaneous coronary intervention comprised approximately 80% of procedures. After a mean follow-up time of approximately 5 years, 41 deaths (2.2 per 100 person-years) occurred in women with previous maternal placental syndromes and 83 deaths (1.1 per 100 person-years) in women without maternal placental syndrome (adjusted hazard ratio, 1.96; 95% confidence interval, 1.29-2.99). Of the maternal placental syndrome subtypes, the risk of death was significant in women with placental abruption (adjusted hazard ratio, 2.79; 95% confidence interval, 1.31-5.96), placental infarction (adjusted hazard ratio, 3.09; 95% confidence interval, 1.23 7.74), and preeclampsia (adjusted hazard ratio, 1.61; 95% confidence interval, 1.00-2.58). Women with maternal placental syndrome in >=2 pregnancies had the highest adjusted hazard ratio of death (4.31; 95% confidence interval, 1.71 10.89). CONCLUSION: In middle-aged women who undergo coronary revascularization, previous maternal placental syndrome doubles the risk of death; recurrent maternal placental syndrome quadruples that risk. Some covariates and secondary measures may not have been well-captured and classified herein, leading to residual confounding. PMID- 26283455 TI - Early onset preeclampsia and cerebral palsy: a double hit model? AB - BACKGROUND: Cerebral palsy (CP) is a late sequel of pregnancy, and the role of preeclampsia is debatable. OBJECTIVE: The aims of this study were to determine the association between preeclampsia and cerebral palsy and to determine the risk factors for the development of cerebral palsy in these patients. STUDY DESIGN: A retrospective population-based cohort study was designed that included 229,192 singleton pregnancies. The study population was divided into 2 groups: (1) patients with preeclampsia (n = 9749) and (2) normotensive gestations (n = 219,443). Generalized Estimating Equation multiple logistic regression models were performed to study the associations among preeclampsia, small for gestational age, gestational age at delivery, and the risk factors for the development of cerebral palsy in neonates of women with preeclampsia. RESULTS: The rate of cerebral palsy was double in patients with preeclampsia than in the normotensive group (0.2% vs 0.1%; P = .015); early onset preeclampsia and small for gestational age were independent risk factors for the subsequent development of cerebral palsy (odds ratio, 8.639 [95% confidence interval, 4.269-17.480]; odds ratio, 2.737 [95% confidence interval, 1.937-3.868], respectively). A second model was conducted to determine the risk factors for the development of cerebral palsy in women with preeclampsia. Birth asphyxia, complications of prematurity, and neonatal infectious morbidity, but not small for gestational age or gestational age at delivery, were independent risk factors for the development of cerebral palsy. CONCLUSION: In a comparison with normal pregnant women, the rate of cerebral palsy is double among patients with preeclampsia, especially those with early-onset disease. Early-onset preeclampsia is an independent risk factor for cerebral palsy. Among women with preeclampsia, the presence of neonatal infectious morbidity, birth asphyxia, and complications of prematurity are independent risk factors for the development of cerebral palsy, which further supports the role of a multi-hit model in the pathogenesis of this syndrome. PMID- 26283456 TI - Reply: To PMID 25448524. PMID- 26283457 TI - Black-white differences in severe maternal morbidity and site of care. AB - BACKGROUND: For every maternal death, >100 women experience severe maternal morbidity, which is a life-threatening diagnosis, or undergo a life-saving procedure during their delivery hospitalization. Similar to racial/ethnic disparities in maternal death, black women are more likely to experience severe maternal morbidity than white women. Site of care has received attention as a mechanism to explain disparities in other areas of medicine. Data indicate that black women receive care in a concentrated set of hospitals and that these hospitals appear to provide lower quality of care. Whether racial differences in the site of delivery contribute to observed black-white disparities in severe maternal morbidity rates is unknown. OBJECTIVE: The purpose of this study was to determine whether hospitals with high proportions of black deliveries have higher severe maternal morbidity and whether such differences contribute to overall black-white disparities in severe maternal morbidity. STUDY DESIGN: We used a published algorithm to identify cases of severe maternal morbidity during deliveries in the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project for 2010 and 2011. We ranked hospitals by their proportion of black deliveries into high black-serving (top 5%), medium black-serving (5% to 25% range), and low black-serving hospitals. We analyzed the risks of severe maternal morbidity for black and white women by hospital black-serving status using logistic regressions that were adjusted for patient characteristics, comorbidities, hospital characteristics, and within-hospital clustering. We then derived adjusted rates from these models. RESULTS: Seventy-four percent of black deliveries occurred at high and medium black-serving hospitals. Overall, severe maternal morbidity occurred more frequently among black than white women (25.8 vs 11.8 per 1000 deliveries, respectively; P < .001); after adjustment for the distribution of patient characteristics and comorbidities, this differential declined but remained elevated (18.8 vs 13.3 per 1000 deliveries, respectively; P < .001). Women who delivered in high and medium black-serving hospitals had elevated rates of severe maternal morbidity rates compared with those in low black-serving hospitals in unadjusted (29.4 and 19.4 vs 12.2 per 1000 deliveries, respectively; P < .001) and adjusted analyses (17.3 and 16.5 vs 13.5 per 1000 deliveries, respectively; P < .001). Black women who delivered at high black serving hospitals had the highest risk of poor outcomes. CONCLUSION: Most black deliveries occur in a concentrated set of hospitals, and these hospitals have higher severe maternal morbidity rates. Targeting quality improvement efforts at these hospitals may improve care for all deliveries and disproportionately impact care for black women. PMID- 26283459 TI - Impact of a robotic simulation program on resident surgical performance. PMID- 26283458 TI - Antenatal corticosteroid timing: accuracy after the introduction of a rescue course protocol. AB - BACKGROUND: Antenatal corticosteroid administration is a critical fetal intervention, and the use of a rescue protocol is now standard practice. Rescue antenatal corticosteroid may improve overall accuracy of antenatal corticosteroid administration timing, but this observation and its effect on the initial course is unknown. OBJECTIVE: We sought to compare the accuracy of antenatal corticosteroid administration before and after the implementation of a rescue antenatal corticosteroid protocol. STUDY DESIGN: We performed a retrospective cohort study of patients who received a minimum of 1 dose of antenatal corticosteroid from 2006-2012 at the University of Washington Medical Center with the use of the University of Washington Medical Center Pharmacy Database. For inclusion, subjects were required to be admitted, receive the initial antenatal corticosteroid course at 24-34 weeks gestation, and deliver at University of Washington Medical Center. We designated 2 groups that were based on when rescue antenatal corticosteroid became standard practice at University of Washington Medical Center: before rescue antenatal corticosteroid (2006-2008) and after rescue antenatal corticosteroid (2009-2012). Primary outcome was delivery within any optimal antenatal corticosteroid window, which was defined as 48 hours to 7 days after the first dose or third dose. We also compared delivery within the optimal window of the initial and rescue antenatal corticosteroid courses independently and assessed antenatal corticosteroid timing by the indication for delivery. Chi squared and independent sample t-tests were used to compare results. RESULTS: From 2006-2012, 1356 women met inclusion criteria, 601 before and 755 after rescue antenatal corticosteroid. The study groups demonstrated similar demographics, with the exception of more white women in the group after rescue antenatal corticosteroid (47% vs 60%; P < .01) and delivered at comparable gestational ages (32.7 vs 32.6 weeks; P = .59). Availability of a second course did not increase total subjects who delivered within any optimal window (26.5% vs 28.5%; P = .41). Frequency of delivery within the initial course optimal window did not change after the introduction of the rescue course protocol (26.1% vs 26.4%; P = .92). Similarly, of the 73 subjects who received rescue antenatal corticosteroid, 24.7% delivered in the optimal window of the second course. Delivery within the optimal window varied by indication for antenatal corticosteroid, with highest accuracy among maternal indications (41.2% in any optimal window), followed by preterm premature rupture of membranes (32.1%). Lowest administration accuracy was among women with antenatal cervical shortening and advanced cervical dilation; only 2.8% and 6.3% delivered within the optimal window, respectively. Furthermore, for women with antenatal cervical shortening, the mean gestational age of delivery was 35.1 weeks, and the median interval from antenatal corticosteroid administration to delivery was 55 days (interquartile range, 34-72 days). CONCLUSIONS: The opportunity for a second course of antenatal corticosteroid did not improve the number of women who delivered within any optimal antenatal corticosteroid window. Administration timing was similar for the initial course and the rescue course, with approximately one-quarter of women delivering within the optimal antenatal corticosteroid window. These findings likely reflect the few circumstances in which rescue antenatal corticosteroid is useful and the poor predictability of preterm birth. Future focus should be aimed at tools to predict the timing of preterm birth to optimize antenatal corticosteroid administration. PMID- 26283460 TI - Impact of co-existent thyroiditis on clinical outcome in papillary thyroid carcinoma with high preoperative serum antithyroglobulin antibody: a retrospective cohort study. AB - OBJECTIVES: The aim of this study was to investigate the impact of co-existent chronic lymphocytic thyroiditis (CLT) on changes in serum antithyroglobulin antibody (TgAb) and clinical outcome in papillary thyroid carcinoma (PTC) patients with high preoperative serum TgAb. DESIGN: A retrospective cohort study. SETTING: University teaching hospital. PARTICIPANTS: Thirty-seven PTC patients with high preoperative serum TgAb level (>=100 U/mL) were evaluated. All patients underwent total thyroidectomy followed by high-dose I-131 ablation. MAIN OUTCOME MEASURES: Per cent changes of TgAb between pre-treatment and post-treatment, and disease-free survival were calculated. RESULTS: Twenty-two patients (59.5%) had co-existent CLT, and seven had residual/recurrent tumours. There was a higher proportion of females among the patients with CLT compared to those without CLT (95.5% versus 66.7%; P = 0.0306). There were trends towards more aggressive pathologies, such as tumour size, extrathyroidal extension, surgical margin and lymph node stage, in PTC without CLT than in that with co-existent CLT. Pre treatment and post-treatment TgAb were all higher in PTC with co-existent CLT. But, per cent changes of TgAb between pre-treatment and post-treatment were no significant difference between PTC with and without CLT (P < 0.05). Patients with co-existent CLT showed a significantly lower residual/recurrent tumour rate than those without CLT (4.5% versus 40%; P = 0.0113). CONCLUSION: Residual/recurrent tumour rate was lower in PTC patients with co-existent CLT than in those without CLT. PMID- 26283462 TI - Spatio-temporal elements of articulation work in the achievement of repeat prescribing safety in UK general practice. AB - Prescribing is the most common healthcare intervention, and is both beneficial and risky. An important source of risk in UK general practice is the management of 'repeat prescriptions', which are typically requested from and issued by non clinically trained reception staff with only intermittent reauthorisation by a clinical prescriber. This paper ethnographically examines the formal and informal work employed by GPs and receptionists to safely conduct repeat prescribing work in primary care using Strauss's (1985, 1988, 1993) concept of 'articulation work' across eight UK general practices. The analytical lens of articulation work provided an investigative framing to contextually map the informal, invisible resources of resilience and strength employed by practice team members in the achievement of repeat prescribing safety, where risk and vulnerability were continually relocated across space and time. In particular, the paper makes visible the micro-level competencies and collaborative practices that were routinely employed by both GPs and receptionists across different socio-cultural contexts, with informal, cross-hierarchical communication usually considered more effective than the formal structures of communication that existed (e.g. protocols). While GPs held formal prescribing authority, this paper also examines the key role of receptionists in both the initiation and safe coordination of the repeat prescribing routine. PMID- 26283461 TI - Group cognitive behavioural treatment of youth anxiety in community based clinical practice: Clinical significance and benchmarking against efficacy. AB - The efficacy of a group cognitive behavioural therapy (CBT) programme (Cool Kids) of youth anxiety has been demonstrated at university clinics in Australia and Denmark and similar CBT programmes have been found effective within community settings in other countries. However, most effectiveness studies of CBT for youth anxiety have either used a mixture of CBT guidelines, or translated protocols not previous tested in an efficacy trial. This study used a benchmarking strategy to compare outcomes from the same CBT programme used at a university research clinic (N=87) and community centres (N=82). There was a significant reduction on both clinical and self-report measures of youth anxiety over time with medium to large effect sizes within both samples. Treatment effects on self-report measures of youth anxiety were significantly larger within the university sample, while changes in clinical measures of youth anxiety were similar in the two samples. Overall these findings suggest that an efficacious CBT group treatment programme developed within research contexts is transportable to community centres. Despite being effective within the community, the results indicate that the treatment may lose some of its efficacy when disseminated to the community. PMID- 26283464 TI - Dicrocoelium dendriticum induces autophagic vacuoles accumulation in human hepatocarcinoma cells. AB - The relationship between Dicrocoelium dendriticum and cancer has been poorly investigated so far, but a large amount of findings suggest that other trematodes can favour cancer in both animals and humans. In this study, the effects of D. dendriticum on cell proliferation, cell death mechanisms and oxidative stress induction were evaluated in hepatocellular carcinoma (HCC) cell lines (HepG2 and HuH7). Results showed that short time exposure to low concentrations of somatic antigens from D. dendriticum caused slight proliferation in both HepG2 and HuH7 cells while high concentrations and long exposure time to extracts from D. dendriticum caused a significant growth inhibition. This effect was, however, not paralleled by apoptosis but it occurred with an about 40% increase of the formation of autophagic vacuoles. In the same experimental conditions, a strong oxidative stress was recorded with an about 100% increase of the intracellular O(2-). These data suggest the occurrence of an escape anti-apoptotic mechanism in HCC cells. In conclusion, these results suggest a role for D. dendriticum in the chronic oxidative stress and in the regulation of transformation processes in HCC warranting additional investigations in this specific area of research. PMID- 26283463 TI - Abnormal retinal development in Cloche mutant zebrafish. AB - BACKGROUND: Functions for the early embryonic vasculature in regulating development of central nervous system tissues, such as the retina, have been suggested by in vitro studies and by in vivo manipulations that caused additional ocular vessels to develop. Here, we use an avascular zebrafish embryo, cloche-/- (clo-/-), to begin to identify necessary developmental functions of the ocular vasculature in regulating development and patterning of the neural retina, in vivo. These studies are possible in zebrafish embryos, which do not yet rely upon the vasculature for tissue oxygenation. RESULTS: clo-/- embryos lacked early ocular vasculature and were microphthalmic, with reduced retinal cell proliferation and cell survival. Retinas of clo mutants were disorganized, with irregular synaptic layers, mispatterned expression domains of retinal transcription factors, morphologically abnormal Muller glia, reduced differentiation of specific retinal cell types, and sporadically distributed cone photoreceptors. Blockade of p53-mediated cell death did not completely rescue this phenotype and revealed ectopic cones in the inner nuclear layer. clo-/- embryos did not upregulate a molecular marker for hypoxia. CONCLUSIONS: The disorganized retinal phenotype of clo-/- embryos is consistent with a neural and glial developmental patterning role for the early ocular vasculature that is independent of its eventual function in gas exchange. PMID- 26283465 TI - The influence of Nosema (Microspora: Nosematidae) infection on honey bee (Hymenoptera: Apidae) defense against Varroa destructor (Mesostigmata: Varroidae). AB - The objectives of this study were to quantify the costs and benefits of co parasitism with Varroa (Varroa destructor Anderson and Trueman) and Nosema (Nosema ceranae Fries and Nosema apis Zander) on honey bees (Apis mellifera L.) with different defense levels. Newly-emerged worker bees from either high-mite mortality-rate (high-MMR) bees or low-mite-mortality-rate (low-MMR) bees were confined in forty bioassay cages which were either inoculated with Nosema spores [Nosema (+) group] or were left un-inoculated [Nosema (-) group]. Caged-bees were then inoculated with Varroa mites [Varroa (+) group] or were left untreated [Varroa (-) group]. This established four treatment combinations within each Nosema treatment group: (1) low-MMR Varroa (-), (2) high-MMR Varroa (-), (3) low MMR Varroa (+) and (4) high-MMR Varroa (+), each with five replicates. Overall mite mortality in high-MMR bees (0.12+/-0.02 mites per day) was significantly greater than in the low-MMR bees (0.06+/-0.02 mites per day). In the Nosema (-) groups bee mortality was greater in high-MMR bees than low-MMR bees but only when bees had a higher mite burden. Overall, high-MMR bees in the Nosema (-) group showed greater reductions in mean abundance of mites over time compared with low MMR bees, when inoculated with additional mites. However, high-MMR bees could not reduce mite load as well as in the Nosema (-) group when fed with Nosema spores. Mean abundance of Nosema spores in live bees and dead bees of both strains of bees was significantly greater in the Nosema (+) group. Molecular analyses confirmed the presence of both Nosema species in inoculated bees but N. ceranae was more abundant than N. apis and unlike N. apis increased over the course of the experiment. Collectively, this study showed differential mite mortality rates among different genotypes of bees, however, Nosema infection restrained Varroa removal success in high-MMR bees. PMID- 26283466 TI - Potential of native Beauveria pseudobassiana strain for biological control of Pine Wood Nematode vector Monochamus galloprovincialis. AB - Three entomopathogenic fungal strains, Isaria farinosa (Holmsk.) Fr., Lecanicillium attenuatum (Zare & W. Games) and Beauveria pseudobassiana (Bals.) Vuill. were isolated in Spain from naturally infected Monochamus galloprovincialis (Olivier) (Coleoptera: Cerambycidae), the European vector of Pine Wilt Disease (PWD). This is the first time that these entomopathogenic fungi have been isolated from M. galloprovincialis beetles. Assays showed the B. pseudobassiana EABps 11/01-Mg strain to be highly virulent against the pine sawyer. Horizontal and vertical transmission were assessed for both aqueous (1*10(8)conidia/ml) and dry (4.25*10(9)conidia/g) conidial formulations. Evidence of horizontal or vertical transmission was not found when insects were inoculated with the aqueous conidial suspension. However, when dry conidia were applied, 100% of the horizontally-infected insects died and their average survival times (AST) were significantly reduced (from 21.10 and 25.00 days in controls to 10.40 and 10.00 days in infected males and females, respectively). Compared to control females, numbers of egg-laying wounds, eggs laid, live larvae after 5 days and larvae entering the xylem after 6 months were significantly reduced in both inoculated females and clean females that had mated with inoculated males, pointing to horizontally-induced reduction of progeny. These results validate the potential of the isolated B. pseudobassiana strain as an important natural population regulator. Through auto-dissemination techniques, it could be used for the integrated control of Pine Wood Nematode vectors and constitute a new tool for Pine Wilt Disease management. PMID- 26283467 TI - The outcome of white matter abnormalities in early treated phenylketonuric patients: A retrospective longitudinal long-term study. AB - BACKGROUND: Pathogenesis and clinical consequences of white matter abnormalities on magnetic resonance imaging (MRI) in phenylketonuric (PKU) patients are incompletely known. OBJECTIVE: To study white matter alterations progression and outcome and its relationships with phenylalanine levels and intelligence quotient (IQ) in early treated PKU subjects who underwent serial MRIs during a prolonged follow-up. METHODS: 47 early treated PKU patients (mean age 25.1 +/- 5.6 years; range 12-37 years) have been enrolled when two or more consecutive brain MRIs, a complete biochemical history, and MRI-concurrent blood phenylalanine levels were available. The severity and extension of white matter abnormalities were expressed in a computed score. Consecutive IQ assessments were available in 24 patients. We analyzed intra- and interindividual white matter alterations variations and their relationship with quality of biochemical control and cognitive outcome. RESULTS: Early treated PKU patients showed a high rate of white matter alterations with a relevant increase in frequency/severity from the second decade of life onwards. Age and quality of dietary control before or between subsequent examinations showed an independent cumulative effect on white matter alterations outcome. No significant association was found between white matter alterations and cognitive outcome. A remarkable interindividual variability was found and several patients disclosed incongruity between the trajectory of white matter alterations and biochemical control. About 30% of white matter alterations variability remains unexplained by the disease associated determinants. CONCLUSIONS: The evolution of white matter alterations is not significantly affected by intellectual outcome and is affected by aging, chronic exposure to phenylalanine, and unknown individual factors. PMID- 26283468 TI - Sclerosteosis caused by a novel nonsense mutation of SOST in a consanguineous family. AB - Sclerosteosis, characterized by the hyperostosis of cranial and tubular bones, is a rare autosomal recessive hereditary disorder caused by mutation of SOST gene. Four nonsense mutations of SOST have been identified worldwide. Here, we report two affected siblings who carried a novel nonsense mutation of SOST in a consanguineous family from China. The proband manifested typical symptoms of sclerosteosis, whereas the symptoms were absent in another affected sibling. Two nucleotide substitutions in exon 2 of SOST were identified, c.444_445TC>AA, resulting in a premature stop codon, p.Cys148->Stop. This truncated mutation loses 66 amino acid residues which contain 3 cysteine residues of the cysteine knot motif, leading to loss of function of SOST. The symptoms of sclerosteosis may be clinically heterogeneous in some patients, even with the same mutation. Our results support the notion that founder effects from the ancestors contribute to the disease onset. PMID- 26283469 TI - Elevated expression of platelet-derived chemokines in patients with antiphospholipid syndrome. AB - OBJECTIVE: Platelet factor 4 tetramers (CXCL4 chemokine) form complexes with beta2glycoprotein I (beta2GPI), recognized by anti-beta2GPI antibodies leading to platelet activation in antiphospholipid syndrome (APS), either primary (PAPS) or secondary (SAPS). Increased plasma levels of CXCL4 may favor this process; therefore we measured plasma levels of CXCL4, a CXCL4 variant (CXCL4L1) and as controls, platelet-derived chemokines CXCL7 (NAP-2) and CCL5 (RANTES), in APS, and disease controls such as patients with systemic lupus erythematosus (SLE) coronary artery disease (CAD) and healthy donors (HDs). METHODS: Plasma samples and platelets were isolated from patients with APS (n = 87), SLE (n = 29), CAD (n = 14) and 54 HDs. Plasma levels of CXCL4, CXCL4L1, CXCL7 and CCL5 as well as intracellular platelet CXCL4 and CXCL4L1 were measured using ELISA. Platelet CXCL4 and CXCL4L1 RNA levels were determined by RT-PCR. RESULTS: CXCL4, CXCL7 (NAP-2) and CCL5 (RANTES) plasma levels were significantly higher in patients with APS compared to both control groups (SLE, CAD) and HDs. CXCL4L1 plasma levels were also significantly higher in APS than in SLE and HDs, but lower from that of CAD patients. Statistically significant concordance was detected between CXCL4 and CXCL7 (p < 0.0001) or CCL5 (p < 0.0001) plasma levels in patients with APS, either PAPS or SAPS. CXCL4L1 plasma levels were inversely correlated with CXCL4 (P = 0.0027), CXCL7 (p = 0.012) and CCL5 (p = 0.023) in PAPS and positively with CXCL4 (p = 0.0191), CCL5 (p < 0.0001) and CXCL7 (P < 0.0001), in SAPS. Levels of CXCL4, CXCL4L1, CXCL7 and CCL5 were divided in "high" (exceeding a level defined as the mean of HDs and 3 SD) and "low" (below this level); The "CXCL4L1 high" group was characterized by increased IgG aCL, (p = 0.0215), double antibody positivity (either aCL or anti-beta2GPI plus LA), (p = 0.0277), triple antibody positivity (aCL plus anti-beta2GPI plus LA), (p = 0.0073) and thrombocytopenia (p = 0.0061), as well as with at least 1 thrombotic event or the last 5 years (p = 0.0001), or more than 3 thrombotic events ever (p = 0.0151). CONCLUSIONS: Chemokines associated with platelet activation and immune cell chemotaxis were found to be elevated in APS patients' plasma and may contribute to the pathogenesis of the syndrome. High CXCL4L1 plasma levels are associated with the clinical expression of APS and should be prospectively evaluated as a biomarker. PMID- 26283470 TI - Fabrication of Nanocarbon Composites Using In Situ Chemical Vapor Deposition and Their Applications. AB - Nanocarbon (carbon nanotubes (CNTs) and graphene (GN)) composites attract considerable research interest due to their fascinating applications in many fields. Here, recent developments in the field of in situ chemical vapor deposition (CVD) for the design and controlled preparation of advanced nanocarbon composites are highlighted, specifically, CNT-reinforced bulk structural composites, as well as CNT, GN, and CNT/GN functional composites, together with their practical and potential applications. In situ CVD is a very attractive approach for the fabrication of composites because of its engaging features, such as its simplicity, low-cost, versatility, and tunability. The morphologies, structures, dispersion, and interface of the resulting nanocarbon composites can be easily modulated by varying the experimental parameters (such as temperature, catalysts, carbon sources, templates or template catalysts, etc.), which enables a great potential for the in situ synthesis of high-quality nanocarbons with tailored size and dimension for constructing high-performance composites, which has not yet been achieved by conventional methods. In addition, new trends of the in situ CVD toward nanocarbon composites are discussed. PMID- 26283471 TI - Diabetes mellitus and its management with medicinal plants: A perspective based on Iranian research. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Complementary and alternative medicine has been increasingly used to treat chronic illnesses, such as diabetes mellitus. However, various limitations in terms of their application and efficacies exist. Furthermore, there is still much to be done to discover the right herbal medicine for diabetes. AIM OF THE STUDY: This paper aims to evaluate previous herbal studies on the management of diabetes mellitus, to address their strengths and weaknesses and propose a general framework for future studies. APPROACH AND METHODS: Data sources such as PubMed, ScienceDirect, Scopus, SpringerLink, and Wiley were searched, limited to Iran, using 36 search terms such as herbal, traditional, medicine, and phytopharmacy in combination with diabetes and related complications. Reviewed articles were evaluated regarding the use of botanical nomenclature and included information on (1) identity of plants and plant parts used, (2) the processing procedure, and (3) the extraction process. The main outcomes were extracted and then surveyed in terms of the efficacies of herbs in the management of diabetes mellitus. Then a comparative study was performed between Iranian and non-Iranian studies with respect to herbs best studied in Iran. RESULTS: Of the 82 herbs studied in Iran, only six herbs were endemic and 19 were studied in detail. Although most of the reviewed herbs were found to decrease the level of blood glucose (BG) and/or glycated hemoglobin (HbA1C) in both Iranian and non-Iranian studies, information on their pharmacological mechanisms is scarce. However, the level of HbA1C was measured in a limited number of clinical trials or animal studies. Available information on both short- and long-term use of studied herbs on diabetes related complications and functions of involved organs as well as comorbid depression and/or simultaneous changes in lifestyle is also insufficient. Furthermore, little or no information on their phytochemical, toxicological, and herb-drug interaction properties is available. It is worth noting that the efficacy of the reviewed herbs has been studied scarcely in both humans and animals regarding both Iranian and non Iranian studies. A significant number of reviewed articles failed to cite the scientific name of herbs and include information on the processing procedure and the extraction process. CONCLUSIONS: Treatment of diabetes mellitus as a multifactorial disease using herbal medicines requires a comprehensive approach. In order to discover the right herbal medicine for the management of diabetes many other important factors than the levels of BG, HbA1C and insulin should be considered. According to our criteria, all the reviewed herbs suffered from inadequate investigation in human, animal and in vitro models in this respect, whereas they are worth investigating further. However, more research on endemic plants and the traditional history of herbal medicine is warranted. In our opinion, the pharmacological, toxicological, and phytochemical information should be obtained before clinical trials. Furthermore, information such as botanical scientific nomenclature, side effects, and toxicity will improve the quality and validity of publications in herbal research. In particular, designing a database covering all valid information about herbs and/or diseases will decrease unnecessary costs and increase the efficiency of research. PMID- 26283472 TI - Ethnopharmacological relevance of indigenous medicinal plants from district Bahawalnagar, Punjab, Pakistan. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Indigenous plants have played a key role in the treatment of human diseases. This study was aimed to report the indigenous medicinal plants from Bahawalnagar district of Southern Punjab, Pakistan to document the important medicinal plants and herbal preparations. MATERIAL AND METHODS: Rapid appraisal approach (RAA) involved direct interaction with local people and observations during the field visits; was used to collect data during March to June and August to December 2012. RESULTS AND DISCUSSIONS: A total of 63 plants were reported to be effective for ailments treatment in the local healthcare system of the study area, belonging to 56 genera and 34 families. Among families Fabaceae was the predominant by contributing 09 species. CONCLUSION: Plants knowledge is not uniformly distributed among the 488 informants interviewed by mean of questionnaire. PMID- 26283473 TI - Lattice Strain Mapping of Platinum Nanoparticles on Carbon and SnO2 Supports. AB - It is extremely important to understand the properties of supported metal nanoparticles at the atomic scale. In particular, visualizing the interaction between nanoparticle and support, as well as the strain distribution within the particle is highly desirable. Lattice strain can affect catalytic activity, and therefore strain engineering via e.g. synthesis of core-shell nanoparticles or compositional segregation has been intensively studied. However, substrate induced lattice strain has yet to be visualized directly. In this study, platinum nanoparticles decorated on graphitized carbon or tin oxide supports are investigated using spherical aberration-corrected scanning transmission electron microscopy (Cs-corrected STEM) coupled with geometric phase analysis (GPA). Local changes in lattice parameter are observed within the Pt nanoparticles and the strain distribution is mapped. This reveals that Pt nanoparticles on SnO2 are more highly strained than on carbon, especially in the region of atomic steps in the SnO2 lattice. These substrate-induced strain effects are also reproduced in density functional theory simulations, and related to catalytic oxygen reduction reaction activity. This study suggests that tailoring the catalytic activity of electrocatalyst nanoparticles via the strong metal-support interaction (SMSI) is possible. This technique also provides an experimental platform for improving our understanding of nanoparticles at the atomic scale. PMID- 26283474 TI - Do classroom ventilation rates in California elementary schools influence standardized test scores? Results from a prospective study. AB - Limited evidence has associated lower ventilation rates (VRs) in schools with reduced student learning or achievement. We analyzed longitudinal data collected over two school years from 150 classrooms in 28 schools within three California school districts. We estimated daily classroom VRs from real-time indoor carbon dioxide measured by web-connected sensors. School districts provided individual level scores on standard tests in Math and English, and classroom-level demographic data. Analyses assessing learning effects used two VR metrics: average VRs for 30 days prior to tests, and proportion of prior daily VRs above specified thresholds during the year. We estimated relationships between scores and VR metrics in multivariate models with generalized estimating equations. All school districts had median school-year VRs below the California VR standard. Most models showed some positive associations of VRs with test scores; however, estimates varied in magnitude and few 95% confidence intervals excluded the null. Combined-district models estimated statistically significant increases of 0.6 points (P = 0.01) on English tests for each 10% increase in prior 30-day VRs. Estimated increases in Math were of similar magnitude but not statistically significant. Findings suggest potential small positive associations between classroom VRs and learning. PMID- 26283475 TI - Orexin a phosphorylates the gamma-Aminobutyric acid type A receptor beta2 subunit on a serine residue and changes the surface expression of the receptor in SH-SY5Y cells exposed to propofol. AB - Propofol activates the gamma-aminobutyric acid type A receptor (GABAA R) and causes a reversible neurite retraction, leaving a thin, thread-like structure behind; it also reverses the transport of vesicles in rat cortical neurons. The awakening peptide orexin A (OA) inhibits this retraction via phospholipase D (PLD) and protein kinase CE (PKCE). The human SH-SY5Y cells express both GABAA Rs and orexin 1 and 2 receptors. These cells are used to examine the interaction between OA and the GABAA R. The effects of OA are studied with flow cytometry and immunoblotting. This study shows that OA stimulates phosphorylation on the serine residues of the GABAA R beta2 subunit and that the phosphorylation is caused by the activation of PLD and PKCE. OA administration followed by propofol reduces the cell surface expression of the GABAA R, whereas propofol stimulation before OA increases the surface expression. The GABAA R beta2 subunit is important for receptor recirculation, and the effect of OA on propofol-stimulated cells may be due to a disturbed recirculation of the GABAA R. PMID- 26283476 TI - Politics in evaluation: Politically responsive evaluation in high stakes environments. AB - The role of politics has often been discussed in evaluation theory and practice. The political influence of the situation can have major effects on the evaluation design, approach and methods. Politics also has the potential to influence the decisions made from the evaluation findings. The current study focuses on the influence of the political context on stakeholder decision making. Utilizing a simulation scenario, this study compares stakeholder decision making in high and low stakes evaluation contexts. Findings suggest that high stakes political environments are more likely than low stakes environments to lead to reduced reliance on technically appropriate measures and increased dependence on measures better reflect the broader political environment. PMID- 26283477 TI - Impact of Toxoplasma gondii on Dendritic Cell Subset Function in the Intestinal Mucosa. AB - The function of mucosal dendritic cell (DC) subsets in immunity and inflammation is not well understood. In this study, we define four DC subsets present within the lamina propria and mesenteric lymph node compartments based on expression of CD103 and CD11b. Using IL-12p40 YFP (Yet40) reporter mice, we show that CD103(+)CD11b(-) mucosal DCs are primary in vivo sources of IL-12p40; we also identified CD103(-)CD11b(-) mucosal DCs as a novel population producing this cytokine. Infection was preferentially found in CD11b(+) DCs that were negative for CD103. Lamina propria DCs containing parasites were negative for IL-12p40. Instead, production of the cytokine was strictly a property of noninfected cells. We also show that vitamin A metabolism, as measured by ALDH activity, was preferentially found in CD103(+)CD11b(+) DC and was strongly downregulated in all mucosal DC subsets during infection. Finally, overall apoptosis of lamina propria DC subsets was increased during infection. Combined, these results highlight the ability of intestinal Toxoplasma infection to alter mucosal DC activity at both the whole population level and at the level of individual subsets. PMID- 26283478 TI - Antimony-Resistant Leishmania donovani Exploits miR-466i To Deactivate Host MyD88 for Regulating IL-10/IL-12 Levels during Early Hours of Infection. AB - Infection with antimony-resistant Leishmania donovani (Sb(R)LD) induces aggressive pathology in the mammalian hosts as compared with ones with antimony sensitive L. donovani (Sb(S)LD) infection. Sb(R)LD, but not Sb(S)LD, interacts with TLR2/TLR6 to induce IL-10 by exploiting p50/c-Rel subunits of NF-kappaB in infected macrophages (Mphis). Most of the TLRs exploit the universal adaptor protein MyD88 to activate NF-kappaB. We now show that infection of Mphis from MyD88(-/-) mice with Sb(R)LD gave rise to significantly higher intracellular parasite number coupled with elevated IL-10/IL-12 ratio in the culture supernatant as compared with infection in wild type (WT) Mphis. Tauhese attributes were not seen with Sb(S)LD in similar experiments. Further, Sb(R)LD infection upregulated miR-466i, which binds with 3'-untranslated region, leading to the downregulation of MyD88. Infection of MyD88(-/-) Mphi or IL-12(-/-) Mphi with Sb(R)LD induced IL-10 surge at 4 h, whereas the same in WT Mphi started from 12 h. Thus, absence of IL-12 in MyD88(-/-) mice favored early binding of NF kappaB subunits to the IL-10 promoter, resulting in IL-10 surge. Infection of MyD88(-/-) mice with Sb(R)LD showed significantly higher organ parasites coupled with ill-defined and immature hepatic granulomas, whereas in WT mice there were less organ parasites and the granulomas were well defined. From the survival kinetics it was observed that Sb(R)LD-infected MyD88(-/-) mice died by 60 d postinfection, whereas the WT mice continued to survive. Our results demonstrate that Sb(R)LD has evolved a unique strategy to evade host antileishmanial immune repertoire by manipulating host MyD88 to its advantage. PMID- 26283479 TI - The Presence and Preferential Activation of Regulatory T Cells Diminish Adoptive Transfer of Autoimmune Diabetes by Polyclonal Nonobese Diabetic (NOD) T Cell Effectors into NSG versus NOD-scid Mice. AB - NOD-scid.Il2rg(null) (NSG) mice are currently being used as recipients to screen for pathogenic autoreactive T cells in type 1 diabetes (T1D) patients. We questioned whether the restriction of IL-2R gamma-chain (Il-2rgamma)-dependent cytokine signaling only to donor cells in NSG recipients differently influenced the activities of transferred diabetogenic T cells when they were introduced as a monoclonal/oligoclonal population versus being part of a polyclonal repertoire. Unexpectedly, a significantly decreased T1D transfer by splenocytes from prediabetic NOD donors was observed in Il-2rgamma(null)-NSG versus Il-2rgamma intact standard NOD-scid recipients. In contrast, NOD-derived monoclonal/oligoclonal TCR transgenic beta cell-autoreactive T cells in either the CD8 (AI4, NY8.3) or CD4 (BDC2.5) compartments transferred disease significantly more rapidly to NSG than to NOD-scid recipients. The reduced diabetes transfer efficiency by polyclonal T cells in NSG recipients was associated with enhanced activation of regulatory T cells (Tregs) mediated by NSG myeloid APC. This enhanced suppressor activity was associated with higher levels of Treg GITR expression in the presence of NSG than NOD-scid APC. These collective results indicate NSG recipients might be efficiently employed to test the activity of T1D patient-derived beta cell-autoreactive T cell clones and lines, but, when screening for pathogenic effectors within polyclonal populations, Tregs should be removed from the transfer inoculum to avoid false negative results. PMID- 26283480 TI - The Human NK Cell Response to Yellow Fever Virus 17D Is Primarily Governed by NK Cell Differentiation Independently of NK Cell Education. AB - NK cells play an important role in the defense against viral infections. However, little is known about the regulation of NK cell responses during the first days of acute viral infections in humans. In this study, we used the live attenuated yellow fever virus (YFV) vaccine 17D as a human in vivo model to study the temporal dynamics and regulation of NK cell responses in an acute viral infection. YFV induced a robust NK cell response in vivo, with an early activation and peak in NK cell function at day 6, followed by a delayed peak in Ki67 expression, which was indicative of proliferation, at day 10. The in vivo NK cell response correlated positively with plasma type I/III IFN levels at day 6, as well as with the viral load. YFV induced an increased functional responsiveness to IL-12 and IL-18, as well as to K562 cells, indicating that the NK cells were primed in vivo. The NK cell responses were associated primarily with the stage of differentiation, because the magnitude of induced Ki67 and CD69 expression was distinctly higher in CD57(-) NK cells. In contrast, NK cells expressing self- and nonself-HLA class I-binding inhibitory killer cell Ig-like receptors contributed, to a similar degree, to the response. Taken together, our results indicate that NK cells are primed by type I/III IFN in vivo early after YFV infection and that their response is governed primarily by the differentiation stage, independently of killer cell Ig-like receptor/HLA class I mediated inhibition or education. PMID- 26283481 TI - Stimulation of the RIG-I/MAVS Pathway by Polyinosinic:Polycytidylic Acid Upregulates IFN-beta in Airway Epithelial Cells with Minimal Costimulation of IL 8. AB - Pharmacological stimulation of the antiviral cytokine IFN-beta in the airways may help to counter deleterious virus-induced exacerbations in chronic inflammatory lung diseases (asthma, chronic obstructive pulmonary disease, or cystic fibrosis). Polyinosinic-polycytidylic acid [poly(I:C)] is a known inducer of IFN beta but also costimulates an inflammatory response. The latter response is undesirable given the pre-existing airway inflammation in these diseases. The objective of our study was to identify conditions for poly(I:C) to selectively upregulate IFN-beta in airway epithelial cells without a concomitant inflammatory response. The inflammatory response was gauged by production of the chemokine IL 8. Using cell lines and primary airway epithelial cells (both submerged and well differentiated), we observed that pure poly(I:C) stimulated IFN-beta mainly through the TLR3/TRIF pathway and IL-8 through an unidentified pathway. The magnitude of the IL-8 response stimulated by pure poly(I:C) matched or even exceeded that of IFN-beta. Furthermore, this IL-8 response could not be pharmacologically downregulated without affecting IFN-beta. In contrast, we show that stimulation of the RIG-I/MAVS pathway, such as when poly(I:C) is delivered intracellularly in a complex with liposomes or via nucleofection, selectively stimulates IFN-beta with low IL-8 costimulation. The magnitude of IFN-beta stimulation by liposome-encapsulated poly(I:C) is markedly diminished in well differentiated cells. In conclusion, it is feasible to augment IFN-beta production in airway epithelial cells without excessive costimulation of IL-8 if the RIG-I/MAVS pathway is stimulated, such as via liposomal delivery of poly(I:C). Better cytoplasmic delivery vehicles are needed to efficiently stimulate this pathway in well-differentiated cells. PMID- 26283483 TI - Retraction Note to: siRNA-participated chemotherapy: an efficient and specific therapeutic against gastric cancer. PMID- 26283484 TI - The Utility of Computed Tomography in Shunted Patients with Idiopathic Intracranial Hypertension Presenting to the Emergency Department. AB - BACKGROUND: Shunted patients with idiopathic intracranial hypertension (IIH) often present to the emergency department (ED) for symptoms related to their disease. Although brain imaging with computed tomography (CT) is often performed, particularly in the current medicolegal environment, its utility during these ED visits is unclear. METHODS: The ED visits of all shunted adult patients with IIH from 2003-2015 were retrospectively reviewed. ED visits not related to IIH were excluded from our study. RESULTS: Thirty-one patients visited the ED 171 times for IIH symptoms. Five patients had greater than 10 ED visits. Twenty-five (81%) patients had 131 visits involving a CT scan, while six (19%) patients were not scanned. The majority of scans (n = 126, 96%) showed no change; five (4%) scans detected new noncritical pathologies. On the basis of CT findings alone, treatment changes occurred in three (2.3%) instances. Of the 131 visits with a CT scan, twenty-five (19%) visits resulted in management changes; of the 40 ED visits without a CT scan, four (10%) visits resulted in a management change (P = 0.23). CONCLUSIONS: In our cohort, CT imaging rarely showed a change in pathology or affected the management of patients with IIH. There was no difference in the rate of management changes between those patients who underwent a CT scan and those who did not. Given the risk of cumulative radiation exposure and cost of CT scans, CT imaging should be used when there is concern for visual dysfunction and the utility of CT imaging in the ED for the workup of other symptoms related to IIH must be explored further. PMID- 26283482 TI - The Novel Receptor C5aR2 Is Required for C5a-Mediated Human Mast Cell Adhesion, Migration, and Proinflammatory Mediator Production. AB - C5a generated during complement activation possesses proinflammatory and immunoregulatory properties critical for the development and modulation of allergic immune responses. In immune cells, C5a mediates its effects through binding to two G protein-coupled receptors, C5aR1 and C5aR2. Mast cells are key effectors in allergic reactions, and decades of research have suggested that the majority of C5a effects on mast cells are mediated through C5aR1, whereas the expression and function of C5aR2 have not been explored. We demonstrated that the human mast cell line Laboratory of Allergic Diseases 2 (LAD2) expresses surface C5aR2 but not C5aR1, whereas CD34(+) cell-derived primary mast cells do not express surface C5aR1 or C5aR2. Stem cell factor and IL-4 upregulated C5aR2 expression on LAD2 cells. Furthermore, C5a caused internalization of LAD2 cell surface C5aR2. We therefore used LAD2 cells as a model to study C5a/C5aR2-induced biological responses and signaling in human mast cells. We found that whereas C5a was unable to induce degranulation, it stimulated GM-CSF, TNF, CXCL10, and CCL2 production. C5a caused ERK phosphorylation, a signaling molecule important in cytokine and chemokine generation. In addition, C5a stimulated adhesion and chemotaxis of mast cells. Wortmannin, an inhibitor of PI3K, and small interfering RNA against beta-arrestin-2 blocked C5a-induced adhesion. Silencing of C5aR2 using lentiviral short hairpin RNA rendered the cells unresponsive to C5a-induced adhesion, chemotaxis, and mediator release, as well as ERK phosphorylation. Overall, this study reveals a novel role for C5aR2 in C5a-mediated activation of mast cells and demonstrates that C5aR2 ligation initiates a beta-arrestin-2-, PI3K-, and ERK-dependent signaling pathway in these cells. PMID- 26283485 TI - Low Rate of Intraoperative Seizures During Awake Craniotomy in a Prospective Cohort with 374 Supratentorial Brain Lesions: Electrocorticography Is Not Mandatory. AB - OBJECTIVE: Awake craniotomy (AC) in brain lesions has allowed an improvement of both oncologic and functional results. However, intraoperative seizures (IOSs) were reported as a cause of failure of AC. Here, we analyze the incidence, risk factors, and consequences of IOSs in a prospective cohort of 374 ACs without electrocorticography (ECoG). METHODS: We performed a prospective study including all patients who underwent AC for an intra-axial supratentorial cerebral lesion from 2009-2014 in our department. Occurrence of IOS was analyzed with respect to medical and epilepsy history, tumor characteristics, operative technique, and postoperative outcomes. RESULTS: The study comprised 374 patients with a major incidence of low-grade glioma (86%). Most of the patients (83%) had epilepsy history before surgery (20% had intractable seizures). Preoperative mean Karnofsky performance scale (KPS) score was 91. IOSs occurred in 13 patients (3.4%). All IOSs were partial seizures, which quickly resolved by irrigation with cold Ringer lactate. No procedure failed because of IOS, and the rate of aborted AC whatever the cause was nil. Mean stimulation current intensity for cortical and subcortical mapping was 2.25 +/- 0.6 mA. Presurgical refractory epilepsy was not associated with a higher incidence of IOS. Three months after surgery, no patients had severe or disabling permanent worsening, even within the IOS group (mean KPS score of 93.7). CONCLUSIONS: AC for intra-axial brain lesion can be safely and reproducibly achieved without ECoG, with a low rate of IOS and excellent functional results, even in patients with preoperative intractable epilepsy. PMID- 26283486 TI - Patient-Reported Outcomes in Elective Cranial Neurosurgery. AB - BACKGROUND: The role of patient-reported outcomes (PROs) in elective cranial neurosurgery has been poorly studied, and their significance in reflecting complication rates is unclear. METHODS: A prospective, consecutive, and unselected cohort of 418 adult patients underwent elective intracranial operations between 7 December, 2011 and 31 December, 2012 in Helsinki University Hospital, Finland. The questionnaire-based PROs included subjective postoperative assessments of overall health, cognitive function, and subjective change in functional status. Outcome measures included in-hospital major morbidity (including mortality) and in-hospital overall morbidity. We compared the usefulness of PROs with postoperative modified Rankin Scale (mRS) score. RESULTS: In univariable analyses, all recorded PROs and 30-day mRS scores >= 3 were associated with in-hospital major and overall morbidity. After multivariable analyses, postoperative deterioration of subjective functional status remained associated with in-hospital major morbidity (P = 0.001, odds ratio [OR] 4.9, confidence interval [CI] 1.9-12.0, sensitivity 71%, and specificity 70%) and overall in-hospital morbidity (P < 0.001, OR 5.7, CI 3.1-10.7, sensitivity 59%, and specificity 84%). Postoperatively impaired functional status was more sensitive but less specific in detecting in-hospital major and overall morbidity than the widely used mRS cut-off value of 2. A simple composite score combining the 3 recorded PROs was highly sensitive and specific in detecting in-hospital major (sensitivity 87%, specificity 98%) and overall (sensitivity 72%, specificity 99%) morbidity. CONCLUSIONS: In elective craniotomy patients, PROs seem promising patient-centered tools for outcomes reporting. Furthermore, neurosurgery-specific patient-reported outcome measures (PROMs) can perhaps be implemented to clinical use to improve patient safety and outcome comparisons in elective cranial neurosurgery. PMID- 26283487 TI - Epidural Bovine Pericardium Facilitates Dissection During Cranioplasty: A Technical Note. AB - BACKGROUND AND OBJECTIVE: Adhesions and scarring of the subcutaneous tissue to the dura mater or dural substitute often complicate cranioplasty. We present our experience with epidural bovine pericardium as a barrier membrane to minimize adhesions and facilitate separation of tissue layers. METHODS: A cohort of patients who underwent decompressive craniectomy and subsequent cranioplasty at a major academic institution in the United States from August 2007 to October 2013 and had epidural bovine pericardium placed as a barrier membrane was retrospectively reviewed. Medical records and imaging studies were reviewed for a number of variables including presence of adhesions, infection, contusions, and operative complications. RESULTS: Twenty-nine patients (male-to-female = 1:1.1; mean age 45 +/- 14.7 years) who underwent decompressive craniectomy with placement of epidural bovine pericardium with subsequent cranioplasty were identified. The median interval between craniectomy and cranioplasty was 64 days, and autologous bone was used for cranioplasty in 86.2% of cases. The average size of cranial defect was 71.2 +/- 28.5 cm(2). At the time of cranioplasty, no or minimal adhesions were found between the subcutaneous tissue and the epidural bovine pericardium. There were 2 (6.9%) infections, 2 (6.9%) patients had contusion after the cranioplasty, and no patient had a complication after cranioplasty that required reoperation. CONCLUSIONS: Epidural bovine pericardium at the time of decompressive craniectomy facilitates dissection at the time of cranioplasty and is not associated with any additional risks. PMID- 26283488 TI - Pediatric Central Nervous System Tumors in Nepal: Retrospective Analysis and Literature Review of Low- and Middle-Income Countries. AB - BACKGROUND: Central nervous system (CNS) tumors are the most common cause of cancer-related death in children. Little is known about the demographics and treatment of pediatric brain tumors in low- and middle-income countries (LMICs). METHODS: We performed a retrospective chart review of all pediatric patients who presented to the neurosurgical service at Tribhuvan University Teaching Hospital in Kathmandu, Nepal from 2009-2014 and collected information on patients <18 years old who received a diagnosis of a CNS tumor. We analyzed age, gender, clinical presentation, extent of surgical resection, histopathology, and length of hospital stay. We also conducted a literature review using specific terminology to capture studies of pediatric neuro-oncologic epidemiology conducted in LMICs. Study location, length of study, sample size, study type, and occurrence of 4 common pediatric brain tumors were extracted. RESULTS: We identified 39 cases of pediatric CNS tumors, with 62.5% observed in male children. We found that male children (median = 13 years) presented later than female children (median = 8 years). The most frequently observed pediatric brain tumor type was ependymoma (17.5%), followed by astrocytoma (15%) and medulloblastoma (15%). Surgical resection was performed for 80% of cases, and gross total resection reported in 62.9% of all surgeries. More than half (54.1%) of patients had symptoms for more than 28 days before seeking treatment. Symptomatic hydrocephalus was noted in 57.1% of children who presented with CNS tumors. The literature review yielded studies from 18 countries. Study length ranged from 2-20 years, and sample sizes varied from 35-1948. Overall, we found more pronounced variation in the relative frequencies of the most common pediatric brain tumors, compared with high-income countries. CONCLUSIONS: We present the first operative series of childhood CNS tumors in Nepal. Children often had delayed diagnosis and treatment of a tumor, despite symptoms. More comprehensive data are required to develop improved treatment and management algorithms in the context of a given country's demographics and medical capabilities for childhood CNS tumors. PMID- 26283489 TI - Mirror Meningioma at Foramen Magnum: A Management Challenge. AB - BACKGROUND: Meningiomas of the foramen magnum are among the most challenging of all skull base lesions. Controversies continue regarding the most appropriate approach to this critical anatomic region. The authors report a first case in English literature about twin meningiomas arising from both sides of the ventrolateral dura at the foramen magnum. CASE DESCRIPTION: Preoperative imaging showed a solitary mass engulfing the lower medulla. However, intraoperatively a twin mass was discovered. It encased the right side vertebral artery (VA) and abutted the left side. The unilateral far lateral transcondylar approach is not enough to resect both tumors at the same time. However, the far lateral transcondylar approach in both sides may compromise the stability and increase the risk of injury to either side of the neurovascular structures. CONCLUSIONS: We suggest that resection can be safely achieved via the unilateral far lateral transcondylar approach followed by Gamma Knife radiosurgery (GKRS) or a staged bilateral approach. PMID- 26283490 TI - Patterns of Failure after Stereotactic Radiosurgery of the Resection Cavity Following Surgical Removal of Brain Metastases. AB - BACKGROUND: Whole brain radiation treatment (WBRT) is considered standard treatment for BM. However, exposing large volumes of normal brain tissue to irradiation can cause neurotoxicity. This study describes our experience with 100 consecutive patients with brain metastases who were managed with surgical extirpation followed by stereotactic radiosurgery (SRS) to the resection cavity. METHODS: Patients with 1-3 brain metastases (BM), who underwent resection of 1-2 BM between June 2005 and December 2013, were treated with SRS directed to the tumor cavity and for any synchronous BM. Local and distant treatment failures were determined based on neuroimaging. Kaplan-Meier curves were generated for local and distant failure rates and overall survival. RESULTS: One hundred and two resection cavities were treated with SRS in 100 consecutive patients. Thirty two additional synchronous metastases were treated in 27 patients during the same session. The median overall survival was 18.9 months. Local control rate at 1 year was 84%. Longer delays between surgery and SRS were associated with increased risk of local failure (hazard ratio, -1.46; P = 0.02). Distant progression occurred in 44% of the patients at a mean of 8.8 +/- 6.6 months after SRS treatment. Ten cases of leptomeningeal spread occurred around the resection cavities (9.8%). Central nervous system failure was not significantly associated with survival. Multivariate Cox regression analysis showed that recursive partitioning analysis and active systemic disease were significantly associated with survival. CONCLUSION: The strategy described provides acceptable local disease control when compared with WBRT following surgery. This approach can delay and even annul WBRT in the majority of selected BM patients, especially recursive partitioning analysis class I patients. SRS should be scheduled as soon as possible after surgery. PMID- 26283491 TI - Livid macules on the forehead after photodynamic therapy. PMID- 26283492 TI - Development of a unit-specific antibiogram and planning for implementation: Preimplementation findings. AB - This practice forum reports experiences with the development of a unit-specific antibiogram and planning for its implementation. Involvement of internal and external facilitators was a key strategy for addressing issues, including data limitations, coordination, and planning. These activities were incorporated and reported as part of the facility's broader antimicrobial stewardship program, and represent the first step in a set of planned projects to evaluate the impact of antibiograms on provider behavior and patient outcomes. PMID- 26283493 TI - Adipose-Derived Stem Cells Expressing the Neurogenin-2 Promote Functional Recovery After Spinal Cord Injury in Rat. AB - Neurogenin2 (Ngn2) is a proneural gene that directs neuronal differentiation of progenitor cells during development. This study aimed to investigate whether the use of adipose-derived stem cells (ADSCs) over-expressing the Ngn2 transgene (Ngn2-ADSCs) could display the characteristics of neurogenic cells and improve functional recovery in an experimental rat model of SCI. ADSCs from rats were cultured and purified in vitro, followed by genetically modified with the Ngn2 gene. Forty-eight adult female Sprague-Dawley rats were randomly assigned to three groups: the control, ADSCs, and Ngn2-ADSCs groups. The hind-limb motor function of all rats was recorded using the Basso, Beattie, and Bresnahan locomotor rating scale for 8 weeks. Moreover, hematoxylineosin staining and immunohistochemistry were also performed. After neural induction, positive expression rate of NeuN in Ngn2-ADSCs group was upon 90 %. Following transplantation, a great number of ADSCs was found around the center of the injury spinal cord at 1 and 4 weeks, which improved retention of tissue at the lesion site. Ngn2-ADSCs differentiated into neurons, indicated by the expression of neuronal markers, NeuN and Tuj1. Additionally, transplantation of Ngn2-ADSCs upregulated the trophic factors (brain-derived neurotrophic factor and vascular endothelial growth factor), and inhibited the glial scar formation, which was indicated by immunohistochemistry with glial fibrillary acidic protein. Finally, Ngn2-ADSCs-treated animals showed the highest functional recovery among the three groups. These findings suggest that transplantation of Ngn2-overexpressed ADSCs promote the functional recovery from SCI, and improve the local microenvironment of injured cord in a more efficient way than that with ADSCs alone. PMID- 26283495 TI - Influence of the ratio of amphiphilic copolymers used as emulsifiers on the microstructure, physical stability and rheology of alpha-pinene emulsions stabilized with gellan gum. AB - alpha-Pinene is a terpenic solvent whose use in the formulation of emulsions entails a double benefit from the environmental point of view since it is a green solvent, easily biodegradable, which also has certain antimicrobial properties. In this work a combination of AtlasTM G-5000 and AtloxTM 4913 amphiphilic copolymers was used to obtain O/W emulsions formulated with alpha-pinene and gellan gum. These emulsions may find applications related to the design of complex biotechnological systems with different uses. In order to investigate the microstructure and the physical stability of these emulsions, a combination of different techniques such as rheology, microscopy, laser diffraction and multiple light scattering turn out to be a useful methodology. The results demonstrated the need to include a minimum amount of AtlasTM G-5000 copolymer in the formulation of these emulsions to improve their stability. These results were supported by the information revealed by optical micrographs, according to which AtlasTM G-5000 is directed to the continuous medium to structure water (this surfactant is particularly effective at forming hydrogen bonds with water). On the other hand AtloxTM 4913 is preferentially adsorbed at the alpha-pinene-water interface, such that a high AtloxTM 4913/AtlasTM G-5000 mass ratio slows down the kinetics of coalescence as shown by multiple light scattering. However, a very low relative concentration of AtlasTM G-5000 causes creaming to become the dominant destabilization mechanism. Increasing the AtlasTM G-5000/AtloxTM 4913 mass ratio yields emulsions with enhanced viscosity and viscoelasticity. PMID- 26283494 TI - Modification of the hydrophilic/hydrophobic characteristic of zein film surfaces by contact with oxygen plasma treated PDMS and oleic acid content. AB - Zein has been widely studied as a biopolymer due to its unique film-forming abilities. Surface properties are of high importance for certain applications which include microfluidics and tissue engineering, as they drastically affect the end result. It is important to develop techniques to modify zein surface properties without compromising bulk material properties. In this study, we developed a facile technique to change the water affinity of zein film surfaces, compatible with patterning techniques via soft lithography. This is achieved by a simple solvent casting technique onto a polydimethylsilohexane (PDMS) substrate that was exposed to oxygen plasma. Water contact angle measurements (WCA) were used to assess the hydrophillicity of zein surfaces and they reached as low as 20 degrees . Atomic force microscopy, optical absorbance and light microscopy were used to study the characteristics of the film and its surface topography. Hydrophilic zein surfaces had higher roughness values compared to hydrophobic ones. Surface roughness, introduced by sandpaper and gratings does not have the same effect as surface chemistry. The amphiphilic nature of plasticizer oleic acid also contributed to the change in the water contact angle of the films. In conclusion, we demonstrated that zein film's surface properties can be controlled by its ability to self-assemble depending on the substrate that it is being cast on. PMID- 26283496 TI - Effect of layer-by-layer coatings and localization of antioxidant on oxidative stability of a model encapsulated bioactive compound in oil-in-water emulsions. AB - Oxidation of encapsulated bioactives in emulsions is one of the key challenges that limit shelf-life of many emulsion containing products. This study seeks to quantify the role of layer-by-layer coatings and localization of antioxidant molecules at the emulsion interface in influencing oxidation of the encapsulated bioactives. Oxidative barrier properties of the emulsions were simulated by measuring the rate of reaction of peroxyl radicals generated in the aqueous phase with the encapsulated radical sensitive dye in the lipid core of the emulsions. The results of peroxyl radical permeation were compared to the stability of encapsulated retinol (model bioactive) in emulsions. To evaluate the role of layer-by-layer coatings in influencing oxidative barrier properties, radical permeation rates and retinol stability were evaluated in emulsion formulations of SDS emulsion and SDS emulsion with one or two layers of polymers (epsilon polylysine and dextran sulfate) coated at the interface. To localize antioxidant molecules to the interface, gallic acid (GA) was chemically conjugated with epsilon-polylysine and subsequently deposited on SDS emulsion based on electrostatic interactions. Emulsion formulations with localized GA molecules at the interface were compared with SDS emulsion with GA molecules in the bulk aqueous phase. The results of this study demonstrate the advantage of localization of antioxidant at the interface and the limited impact of short chain polymer coatings at the interface of emulsions in reducing permeation of radicals and oxidation of a model encapsulated bioactive in oil-in-water emulsions. PMID- 26283497 TI - Antibody-based donor-acceptor spatial reconfiguration in decorated lanthanide doped nanoparticle colloids for the quantification of okadaic acid biotoxin. AB - With the increasing movement away from the mouse bioassay for the detection of toxins in commercially harvested shellfish, there is a growing demand for the development of new and potentially field-deployable tests in its place. In this direction we report the development of a simple and sensitive nanoparticle-based luminescence technique for the detection of the marine biotoxin okadaic acid. Photoluminescent lanthanide nanoparticles were conjugated with fluorophore labelled anti-okadaic acid antibodies which, upon binding to okadaic acid, gave rise to luminescence resonance energy transfer from the nanoparticle to the organic fluorophore dye deriving from a reduction in distance between the two. The intensity ratio of the fluorophore: nanoparticle emission peaks was found to correlate with okadaic acid concentration, and the sensor showed a linear response in the 0.37-3.97 MUM okadaic acid range with a limit of detection of 0.25 MUM. This work may have important implications for the development of new, cheap, and versatile biosensors for a range of biomolecules and that are sufficiently simple to be applied in the field or at point-of-care. PMID- 26283498 TI - Surface functionalization of quantum dots with fine-structured pH-sensitive phospholipid polymer chains. AB - To add novel functionality to quantum dots (QDs), we synthesized water-soluble and pH-responsive block-type polymers by reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymers were composed of cytocompatible 2 methacryloyloxyethyl phosphorylcholine (MPC) polymer segments, which contain a small fraction of active ester groups and can be used to conjugate biologically active compounds to the polymer, and pH-responsive poly(2-(N,N-diethylamino) ethyl methacrylate (DEAEMA)) segments. One terminal of the polymer chain had a hydrophobic alkyl group that originated from the RAFT initiator. This hydrophobic group can bind to the hydrophobic layer on the QD surface. A fluorescent dye was conjugated to the polymer chains via the active ester group. The block-type polymers have an amphiphilic nature in aqueous medium. The polymers were thus easily bound to the QD surface upon evaporation of the solvent from a solution containing the block-type polymer and QDs, yielding QD/fluorescence dye conjugated polymer hybrid nanoparticles. Fluorescence resonance energy transfer (FRET) between the QDs (donors) and the fluorescent dye molecules (acceptors) was used to obtain information on the conformational dynamics of the immobilized polymers. Higher FRET efficiency of the QD/fluorescent dye-conjugated polymer hybrid nanoparticles was observed at pH 7.4 as compared to pH 5.0 due to a stretching-shrinking conformational motion of the poly(DEAEMA) segments in response to changes in pH. We concluded that the block-type MPC polymer-modified nanoparticles could be used to evaluate the pH of cells via FRET fluorescence based on the cytocompatibility of the MPC polymer. PMID- 26283499 TI - Phenylalanine interaction with lipid monolayers at different pHs. AB - The influence of Phe on the surface pressure of 1,2-dipalmitoyl-sn-glycero-3 phosphocholine (DPPC) monolayers at the air-water interface was studied at different initial surface pressures (26 and 40 mN/m) and two pHs (5.0 and 7.3) at constant temperature (20 degrees C). Changes produced by the aminoacid added to the subphase on the surface pressure and on the dipole potential of lipid monolayers were measured at a fixed area. Compressibility properties of the monolayers at different pHs were studied by (pi-A) isotherms. The results suggest that Phe intercalates into a DPPC film at the air-water interface at pH 5 and forms a different arrangement at pH 7.3. The possible relevance of these results of the effect of Phe in physiological conditions is discussed. PMID- 26283500 TI - Dietary restraint of 5-year-old girls: Associations with internalization of the thin ideal and maternal, media, and peer influences. AB - OBJECTIVE: Understanding socio-cultural factors associated with the development of dieting tendencies is important for preventing future disordered eating. We explored individual and socio-cultural factors associated with weight-focussed dietary restraint tendencies (described as dietary restraint) in 5-year-old girls. METHOD: Participants were 111 5-year-old girls and 109 of their mothers. Girls were interviewed about their dietary restraint, body image, appearance ideals, positive weight bias (attributing positive characteristics to thinner figures), and peer conversations. Mothers completed self-report questionnaires assessing dietary restraint and appearance ideals, as well as measures reporting on their daughter's media exposure and peer appearance interest. RESULTS: Thirty four percent of girls reported at least a moderate level of dietary restraint. While most girls were satisfied with their body size, half showed some internalization of the thin ideal. Girls' dietary restraint was correlated with weight bias favoring thinner bodies, and greater internalization of the thin ideal, media exposure, and appearance conversations with peers. Media exposure and appearance conversations were the strongest predictors of dietary restraint. DISCUSSION: These cross-sectional findings suggest that the socio-cultural environment of young girls may be important in the very early development of unhealthy dieting tendencies. Longitudinal research is necessary to identify whether these are prospective risk factors. PMID- 26283501 TI - Vaginal Gene Expression During Treatment With Aromatase Inhibitors. AB - BACKGROUND: Aromatase inhibitor (AI) treatment suppresses estrogen biosynthesis and causes genitourinary symptoms of menopause such as vaginal symptoms, ultimately affecting the quality of life for many postmenopausal women with breast cancer. Thus, the aim of this study was to examine vaginal gene expression in women during treatment with AIs compared with estrogen-treated women. The secondary aim was to study the presence and localization of vaginal aromatase. PATIENTS AND METHODS: Vaginal biopsies were collected from postmenopausal women treated with AIs and from age-matched control women treated with vaginal estrogen therapy. Differential gene expression was studied with the Affymetrix Gene Chip Gene 1.0 ST Array (Affymetrix Inc, Santa Clara, CA) system, Ingenuity pathway analysis, quantitative real-time polymerase chain reaction, and immunohistochemistry. RESULTS: The expression of 279 genes differed between the 2 groups; AI-treated women had low expression of genes involved in cell differentiation, proliferation, and cell adhesion. Some differentially expressed genes were found to interact indirectly with the estrogen receptor alpha. In addition, aromatase protein staining was evident in the basal and the intermediate vaginal epithelium layers, and also in stromal cells with a slightly stronger staining intensity found in AI-treated women. CONCLUSION: In this study, we demonstrated that genes involved in cell differentiation, proliferation, and cell adhesion are differentially expressed in AI-treated women. The expression of vaginal aromatase suggests that this could be the result of local and systemic inhibition of aromatase. Our results emphasize the role of estrogen for vaginal cell differentiation and proliferation and future drug candidates should be aimed at improving cell differentiation and proliferation. PMID- 26283502 TI - Virulence from vesicles: Novel mechanisms of host cell injury by Escherichia coli O104:H4 outbreak strain. AB - The highly virulent Escherichia coli O104:H4 that caused the large 2011 outbreak of diarrhoea and haemolytic uraemic syndrome secretes blended virulence factors of enterohaemorrhagic and enteroaggregative E. coli, but their secretion pathways are unknown. We demonstrate that the outbreak strain releases a cocktail of virulence factors via outer membrane vesicles (OMVs) shed during growth. The OMVs contain Shiga toxin (Stx) 2a, the major virulence factor of the strain, Shigella enterotoxin 1, H4 flagellin, and O104 lipopolysaccharide. The OMVs bind to and are internalised by human intestinal epithelial cells via dynamin-dependent and Stx2a-independent endocytosis, deliver the OMV-associated virulence factors intracellularly and induce caspase-9-mediated apoptosis and interleukin-8 secretion. Stx2a is the key OMV component responsible for the cytotoxicity, whereas flagellin and lipopolysaccharide are the major interleukin-8 inducers. The OMVs represent novel ways for the E. coli O104:H4 outbreak strain to deliver pathogenic cargoes and injure host cells. PMID- 26283503 TI - Thoracic fat volume is independently associated with coronary vasomotion. AB - PURPOSE: Thoracic fat has been associated with an increased risk of coronary artery disease (CAD). As endothelium-dependent vasoreactivity is a surrogate of cardiovascular events and is impaired early in atherosclerosis, we aimed at assessing the possible relationship between thoracic fat volume (TFV) and endothelium-dependent coronary vasomotion. METHODS: Fifty healthy volunteers without known CAD or major cardiovascular risk factors (CRFs) prospectively underwent a (82)Rb cardiac PET/CT to quantify myocardial blood flow (MBF) at rest, and MBF response to cold pressor testing (CPT-MBF) and adenosine (i.e., stress-MBF). TFV was measured by a 2D volumetric CT method and common laboratory blood tests (glucose and insulin levels, HOMA-IR, cholesterol, triglyceride, hsCRP) were performed. Relationships between CPT-MBF, TFV and other CRFs were assessed using non-parametric Spearman rank correlation testing and multivariate linear regression analysis. RESULTS: All of the 50 participants (58 +/- 10y) had normal stress-MBF (2.7 +/- 0.6 mL/min/g; 95 % CI: 2.6-2.9) and myocardial flow reserve (2.8 +/- 0.8; 95 % CI: 2.6-3.0) excluding underlying CAD. Univariate analysis revealed a significant inverse relation between absolute CPT-MBF and sex (rho = -0.47, p = 0.0006), triglyceride (rho = -0.32, p = 0.024) and insulin levels (rho = -0.43, p = 0.0024), HOMA-IR (rho = -0.39, p = 0.007), BMI (rho = 0.51, p = 0.0002) and TFV (rho = -0.52, p = 0.0001). MBF response to adenosine was also correlated with TFV (rho = -0.32, p = 0.026). On multivariate analysis, TFV emerged as the only significant predictor of MBF response to CPT (p = 0.014). CONCLUSIONS: TFV is significantly correlated with endothelium-dependent and independent coronary vasomotion. High TF burden might negatively influence MBF response to CPT and to adenosine stress, even in persons without CAD, suggesting a link between thoracic fat and future cardiovascular events. PMID- 26283504 TI - Baseline and ongoing PET-derived factors predict detrimental effect or potential utility of 18F-FDG PET/CT (FDG-PET/CT) performed for surveillance in asymptomatic lymphoma patients in first remission. AB - PURPOSE: To identify both clinical and FDG PET/CT-derived factors predicting the occurrence of relapse, or conversely, the likelihood of false positive findings in surveillance FDG-PET/CT studies (PETsv). METHODS: The study included 149 asymptomatic patients with Hodgkin's lymphoma (HL) (n = 55) or diffuse large B cell lymphoma (DLBCL) (n = 94) in first remission. PETSv studies were performed 12, 18, 24 and 36 months thereafter. Logistic regression analysis was performed to identify clinical and imaging-derived predictors of either PET-detected relapse or false-positive (FP) results. Tested clinical variables were: 1) age, 2) HL vs. DLBCL, 3) stage of disease, 4) bulky disease, 5) previous radiotherapy. PET/CT-derived variables were: 1) maximum standardized uptake value at baseline, 2) size-incorporated maximum standardized uptake value (SIMaxSUV) at baseline, 3) positive interim PET(PET-2), 4) presence of hot spots likely to be unrelated to the disease in final PET, 5) residual non-FDG avid mass. RESULTS: Accuracy was 88 % for PETsv1, 95 % for PETsv2, 95 % for PETsv3 and 91 % for PETsv4. However, PPV was relatively low in all PETsv. Best predictors of relapse were result of interim PET, HL versus NHL type, SIMaxSUV, age >= 60. Best predictors of FP were previous radiotherapy and hot spots unrelated to the disease in final PET. CONCLUSIONS: The present study confirms the need of restricting the use of surveillance PET/CT to patients at high risk of relapse. Information derived from PET/CT performed at baseline (metabolic disease burden), in the course (PET2) and at the end of therapy (unrelated hot spots) can help to select high-risk patients and also to identify patients more likely to present equivocal findings at PETsv. PMID- 26283505 TI - The role of active brown adipose tissue in human metabolism. AB - PURPOSE: The presence of activated brown adipose tissue (ABAT) has been associated with a reduced risk of obesity in adults. We aimed to investigate whether the presence of ABAT in patients undergoing (18)F-FDG PET/CT examinations was related to blood lipid profiles, liver function, and the prevalence of non alcoholic fatty liver disease (NAFLD). METHODS: We retrospectively and prospectively analysed the (18)F-FDG PET/CT scans from 5,907 consecutive patients who were referred to the Nuclear Medicine Department of the Marmara University School of Medicine from outpatient oncology clinics between July 2008 and June 2014 for a variety of diagnostic reasons. Attenuation coefficients for the liver and spleen were determined for at least five different areas. Blood samples were obtained before PET/CT to assess the blood lipid profiles and liver function. RESULTS: A total of 25 of the 5,907 screened individuals fulfilling the inclusion criteria for the study demonstrated brown fat tissue uptake [ABAT(+) subjects]. After adjustment for potential confounders, 75 individuals without evidence of ABAT on PET [ABAT(-) subjects] were enrolled for comparison purposes. The ABAT(+) group had lower total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase levels (p < 0.01), whereas we found no significant differences in the serum triglyceride and high-density lipoprotein cholesterol levels between the two groups. The prevalence of NAFLD was significantly lower in ABAT(+) than in ABAT(-) subjects (p < 0.01). CONCLUSION: Our study showed that the presence of ABAT in adults had a positive effect on their blood lipid profiles and liver function and was associated with reduced prevalence of NAFLD. Thus, our data suggest that activating brown adipose tissue may be a potential target for preventing and treating dyslipidaemia and NAFLD. PMID- 26283506 TI - Rheological properties of elastomeric impression materials for selective pressure impression technique. AB - PURPOSE: The selective impression technique is recommended for removable prosthodontics. However, the viscoelastic rheological properties of impression materials, particularly the time-dependent viscoelastic changes in impression material immediately after tray seating, are unknown. The objective of this study is to clarify the viscoelastic rheological properties of impression materials by focusing on tray seating. METHODS: In this study, eight types of polyvinylsiloxane (PVS), two types of polyether, and two types of alginate impression materials were used. The storage modulus (G'; degree of stiffness) and loss tangent (tandelta; degree of hardening) were determined as functions of time from 0 to 360 s, commencing immediately after the completion of mixing, using a stress control-type rheometer. Thus, G' and tandelta at 0s and 20 s were compared. RESULTS: Stiffness was found to be widely distributed (4.49-0.26 * 10(4)Pa) among PVS-types, even immediately after mixing the impression material. There was also variation among polyethers (1.55-0.5 * 10(4)Pa) and among alginates (0.64-0.21 * 10(4)Pa). The hardening of all impression materials progresses beyond 20 s after the completion of mixing. CONCLUSIONS: The G' values varied with each impression material, even immediately after mixing, and the accurate impression-taking time was determined from the results of tandelta. These results provide unique insight into the selective impression technique. PMID- 26283507 TI - Loss of occlusal support affects the decline in activities of daily living in elderly people receiving home care. AB - PURPOSE: This study aimed to clarify whether the absence of occlusal support would lead to a decline in the activities of daily living (ADL) in elderly people receiving home care. METHODS: The subjects of this study were 322 elderly individual aged 65 and older who were receiving home care during a one-year observation period. The subjects were divided into two groups according to the change in the total score of the Barthel Index (BI) during the prospective cohort study period (the dependent variable): the maintained/improved activities of daily living group, in which the score was unchanged or improved, and the worsened activities of daily living group, in which the score decreased. The relationship between occlusal status (the presence or absence of occlusal support) at the baseline measurement and each BI score change was evaluated in the slightly, moderately and totally dependent ADL subgroups. RESULTS: The number of subjects in the maintained/improved and the worsened ADL groups was 152 and 170, respectively. The baseline characteristics of cognitive function and occlusal support were significantly different between the maintained/improved and the worsened ADL groups (p < 0.05). Among the ADL subgroups, significantly reduced scores in mobility and toilet use were observed only in the slightly dependent group (p < 0.05). CONCLUSIONS: Our results suggest that the loss of occlusal support may be an important factor in the decline of ADL in elderly people receiving home care, especially slightly dependent people. PMID- 26283509 TI - Pulmonary function in never-smoker patients with chronic rhinosinusitis. AB - BACKGROUND: A close relationship between upper and lower respiratory tract diseases has been reported. The purpose of this study was to evaluate lung function in patients with chronic rhinosinusitis (CRS) who have never smoked. METHODS: A total of 208 patients with CRS were enrolled in this study. Of these subjects, 96 patients were ever smokers and 112 patients were never smokers. CRS patients with lower pulmonary diseases including chronic obstructive pulmonary disease (COPD) and asthma were excluded from this study. Age-matched normal control subjects (n = 55) who were never smokers were also recruited. Pulmonary function testing was performed using spirometry. Lund-Mackay computed tomography (CT) score, peripheral blood eosinophil count, and immunoglobulin E (IgE) level in serum samples were examined. Nasal obstruction was evaluated by active anterior rhinomanometry. RESULTS: CRS patients who were ever smokers have decreased lung function. Never-smoking patients with CRS also showed significant obstructive lung function changes as compared with normal controls. No significant correlation was detected between the clinical parameters (CT score, eosinophil count, IgE level, and nasal resistance) and lung function. CONCLUSION: Asymptomatic obstructive lung function changes were observed in never-smoking patients with CRS. Our findings suggest that patients with CRS should be followed carefully in order to detect lung diseases. PMID- 26283508 TI - Ethanol drives aversive conditioning through dopamine 1 receptor and glutamate receptor-mediated activation of lateral habenula neurons. AB - There has been increasing interest in the lateral habenula (LHb) given its potent regulatory role in many aversion-related behaviors. Interestingly, ethanol can be rewarding as well as aversive; we therefore investigated whether ethanol exposure alters pacemaker firing or glutamate receptor signaling in LHb neurons in vitro and also whether LHb activity in vivo might contribute to the acquisition of conditioned place aversion to ethanol. Surprisingly, in epithalamic slices, low doses of ethanol (1.4 mM) strongly accelerated LHb neuron firing (by ~60%), and ethanol's effects were much reduced by blocking glutamate receptors. Ethanol increased presynaptic glutamate release, and about half of this effect was mediated by dopamine subtype 1 receptors (D1Rs) and cyclic adenosine monophosphate (cAMP)-dependent signaling pathways. In agreement with these findings, c-Fos immunoreactivity in LHb regions was enhanced after a single administration of a low dose of ethanol (0.25 g/kg i.p.). Importantly, the same dose of ethanol in vivo also produced strong conditioned place aversion, and this was prevented by inhibiting D1Rs or neuronal activity within the LHb. By contrast, a higher dose (2 g/kg) led to ethanol conditioned place preference, which was enhanced by inhibiting neuronal activity or D1Rs within the LHb and suppressed by infusing aminomethylphosphonic acid or the D1R agonist SKF38393 within the LHb. Our in vitro and in vivo observations show, for the first time, that ethanol increases LHb excitation, mediated by D1R and glutamate receptors, and may underlie a LHb aversive signal that contributes to ethanol-related aversion. PMID- 26283510 TI - Expanding the chemical space of human serine racemase inhibitors. AB - Serine racemase, the enzyme responsible for d-serine synthesis in the central nervous system, has been identified as a potential therapeutic target to treat N methyl-d-aspartate receptors-related pathologies. The search for specific inhibitors of the enzyme has revealed that serine racemase is a difficult target, with the best inhibitor currently identified, 2,2-dichloromalonate, showing a Ki of 19 MUM. In order to expand the chemical space of hit compounds, we have performed an in silico structure-based screening campaign on a filtered ZINC library applying the FLAP software. The identified hits were docked with GOLD and re-scored with HINT, and the most promising molecules experimentally evaluated on recombinant human serine racemase. Two inhibitors, with chemical structures totally unrelated to inhibitors described so far showed Ki values of about 1.5 mM. PMID- 26283511 TI - Induction of apoptosis by genipin inhibits cell proliferation in AGS human gastric cancer cells via Egr1/p21 signaling pathway. AB - Natural compounds are becoming important candidates in cancer therapy due to their cytotoxic effects on cancer cells by inducing various types of programmed cell deaths. In this study, we investigated whether genipin induces programmed cell deaths and mediates in Egr1/p21 signaling pathways in gastric cancer cells. Effects of genipin in AGS cancer cell lines were observed via evaluation of cell viability, ROS generation, cell cycle arrest, and protein and RNA levels of p21, Egr1, as well as apoptotic marker genes. The cell viability of AGS cells reduced by genipin treatment via induction of the caspase 3-dependent apoptosis. Cell cycle arrest was observed at the G2/M phase along with induction of p21 and p21 dependent cyclins. As an upstream mediator of p21, the transcription factor early growth response-1 (Egr1) upregulated p21 through nuclear translocation and binding to the p21 promoter site. Silencing Egr1 expression inhibited the expression of p21 and downstream molecules involved in apoptosis. We demonstrated that genipin treatment in AGS human gastric cancer cell line induces apoptosis via p53-independent Egr1/p21 signaling pathway in a dose-dependent manner. PMID- 26283512 TI - The Expression of CUGBP1 After Spinal Cord Injury in Rats. AB - CUG-binding protein 1, a member of the CELF (CUGBP and embryonic lethal abnormal vision-like factor) family of RNA-binding proteins, is shown to be multifunctional, regulating many posttranscriptional processes including alternative splicing, deadenylation, mRNA decay, and translation. Recently, CUGBP1 is found to represses p27 IRES activity and inhibits expression of endogenous p27 in cultured breast cancer cells. However, the roles of CUGBP1 in central nervous system injury remain unknown. In our study, we performed acute spinal cord injury (SCI) model in adult rats in order to research the expression changes of CUGBP1 in spinal cord. Western blot analysis showed a marked upregulation of CUGBP1 after SCI. Immunohistochemistry analysis revealed a wide distribution of CUGBP1 in the spinal cord. Double immunofluorescence staining indicated that CUGBP1 immunoreactivity was increased predominantly in neurons and astrocytes after SCI. Moreover, colocalization of CUGBP1/proliferating cell nuclear antigen (PCNA) was detected in GFAP positive cells. We also examined the expression profiles of p27, which was up-regulated after SCI. To further understand whether CUGBP1 plays a role in astrocyte proliferation, we applied LPS to induce astrocyte proliferation in vitro. Western blot analysis demonstrated that CUGBP1 expression was positively correlated with PCNA expression, and the p27 expression was negatively correlated with CUGBP1 expression following LPS stimulation. Our results suggest that CUGBP1 might be implicated in the pathophysiology of spinal cord after SCI. PMID- 26283513 TI - Carbon Tetrachloride Increases the Pro-inflammatory Cytokines Levels in Different Brain Areas of Wistar Rats: The Protective Effect of Acai Frozen Pulp. AB - Acai offers health benefits associated with its high antioxidante capacity, phytochemical composition, nutritional and sensory value. Therefore, the objective of this study was to evaluate the protective effect of acai frozen pulp on carbon tetrachloride (CCl4)-induced damage via modulation of anti- and pro inflammatory cytokines in rat brain tissue. The rats were treated via oral (gavage) daily with water or acai frozen pulp for 14 days at a dose of 7 MUL/g. On the 15th day, the animals in each group received a single intraperitoneal injection of CCl4 in a dose of 3.0 mL/kg or the same volume of mineral oil. After 4 h, the animals were euthanized by decapitation and the cerebral cortex, hippocampus and cerebellum were dissected and homogenated to evaluate the levels of tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), interleukin 18 (IL-18), interleukin 6 (IL-6) and interleukin 10 (IL-10). Data were statistically analyzed by analysis of variance followed by the Tukey post hoc test. It was observed that CCl4 increased TNF-alpha, IL-1beta and IL-18 levels in all brain tissues, and that acai frozen pulp was able to prevent this increase. IL-6 and IL-10 brain tissue levels remained unchanged during all treatments. CCl4 experimental model was suitable to investigate brain tissue anti and pro-inflammatory cytokines. Acai frozen pulp prevented an increase in IL 1beta, IL-18 and TNF-alpha, while IL-6 and IL-10 levels remained unchanged. The precise pathway by which inflammation contribute to hepatic encephalopathy, as well as to how this pathway can be modulated, is still under investigation. PMID- 26283514 TI - diffHic: a Bioconductor package to detect differential genomic interactions in Hi C data. AB - BACKGROUND: Chromatin conformation capture with high-throughput sequencing (Hi-C) is a technique that measures the in vivo intensity of interactions between all pairs of loci in the genome. Most conventional analyses of Hi-C data focus on the detection of statistically significant interactions. However, an alternative strategy involves identifying significant changes in the interaction intensity (i.e., differential interactions) between two or more biological conditions. This is more statistically rigorous and may provide more biologically relevant results. RESULTS: Here, we present the diffHic software package for the detection of differential interactions from Hi-C data. diffHic provides methods for read pair alignment and processing, counting into bin pairs, filtering out low abundance events and normalization of trended or CNV-driven biases. It uses the statistical framework of the edgeR package to model biological variability and to test for significant differences between conditions. Several options for the visualization of results are also included. The use of diffHic is demonstrated with real Hi-C data sets. Performance against existing methods is also evaluated with simulated data. CONCLUSIONS: On real data, diffHic is able to successfully detect interactions with significant differences in intensity between biological conditions. It also compares favourably to existing software tools on simulated data sets. These results suggest that diffHic is a viable approach for differential analyses of Hi-C data. PMID- 26283515 TI - Expression and characterization of a phospholipid hydroperoxide glutathione peroxidase gene in Schistosoma japonicum. AB - Phospholipid hydroperoxide glutathione peroxidase (PHGPx, GPx4) is a major antioxidant enzyme, which plays unique roles in the protection of cells against oxidative stress by catalysing reduction of lipid hydroperoxides. We isolated and characterized a full-length cDNA sequence encoding GPx gene from a blood fluke, Schistosoma japonicum (designated SjGPx), which contained an in-frame TGA codon for selenocysteine (Sec) and a concurrent Sec insertion sequence in its 3' untranslated region. Protein encoded by SjGPx demonstrated a primary structure characteristic to the PHGPx family, including preservation of catalytic domains and absence of the subunit interaction domains. Semi-quantitative reverse transcription PCR and Western blotting showed that the SjGPx was mainly expressed in the female adults and eggs. RNA interference approach was employed to investigate the effects of knockdown of SjGPx. SjGPx expression level was significantly reduced on the 5th day post-RNAi. Significantly reduction in GPx enzyme activities, as well as obvious changes in morphology of intrauterine eggs followed the reduction in SjGPx transcript level. We observed a 63.04% reduction in GPx activity and the eggs severely deformed. Our results revealed that SjGPx protein might be involved in the provision of enzyme activity during egg production. PMID- 26283517 TI - The weathering and transformation process of lead in China's shooting ranges. AB - Corroding steel-core bullets from three shooting ranges in different climate zones of China were collected. Multiple technical methods (EMPA, SEM, XRD, and ICP-OES) were applied to investigate the structure, morphology, and weathering product of this type of bullet in China to analyze the weathering mechanisms in different types of soils. A scanning electron microscope (SEM) was used to view the morphology and microstructure of corrosion layers. On the corroded lead layer surface, unevenness, micro cracks, and spallation were usually present. Around the micro cracks, many types of euhedral and subhedral crystals of the secondary products of lead were formed, most of which were composed of cerussite (PbCO3), while hydrocerussite (Pb3(CO3)2(OH)2) was predominant in the bullet collected from the humid environment. X-ray power diffraction (XRD) results show that the secondary weathering products in the three shooting range soils are clearly different. In the Fangyan shooting range, which has a neutral and semi-arid soil, the lead weathering product was mainly hydrocerussite (Pb3(CO3)2(OH)2), while no substantial amount of crystal phase of lead compound could be found in acidic, damp soils from the Fenghuang shooting range, possibly due to the enhanced dissolution and mobilization of lead compounds at lower pH and higher content of organic matter in the soil. In hot and arid environment of the Baicheng shooting range, cerussite might have undergone thermal decomposition, thus generating shannonite (Pb2O(CO3)). These results indicate that the formation of secondary Pb minerals is largely affected by the climatic zone or the soil properties, which may have implications for range management practices. PMID- 26283516 TI - Working-memory endophenotype and dyslexia-associated genetic variant predict dyslexia phenotype. AB - Developmental dyslexia, a severe impairment of literacy acquisition, is known to have a neurological basis and a strong genetic background. However, effects of individual genetic variations on dyslexia-associated deficits are only moderate and call for the assessment of the genotype's impact on mediating neuro endophenotypes by the imaging genetics approach. Using voxel-based morphometry (VBM) in German participants with and without dyslexia, we investigated gray matter changes and their association with impaired phonological processing, such as reduced verbal working memory. These endophenotypical alterations were, together with dyslexia-associated genetic variations, examined on their suitability as potential predictors of dyslexia. We identified two gray matter clusters in the left posterior temporal cortex related to verbal working memory capacity. Regional cluster differences correlated with genetic risk variants in TNFRSF1B. High-genetic-risk participants exhibit a structural predominance of auditory-association areas relative to auditory-sensory areas, which may partly compensate for deficient early auditory-sensory processing stages of verbal working memory. The reverse regional predominance observed in low-genetic-risk participants may in turn reflect reliance on these early auditory-sensory processing stages. Logistic regression analysis further supported that regional gray matter differences and genetic risk interact in the prediction of individuals' diagnostic status: With increasing genetic risk, the working-memory related structural predominance of auditory-association areas relative to auditory-sensory areas classifies participants with dyslexia versus control participants. Focusing on phonological deficits in dyslexia, our findings suggest endophenotypical changes in the left posterior temporal cortex could comprise novel pathomechanisms for verbal working memory-related processes translating TNFRSF1B genotype into the dyslexia phenotype. PMID- 26283518 TI - Metalloisoporphyrins: from synthesis to applications. AB - An overview of the chemistry of isoporphyrin, the tautomer of porphyrin, whose existence was predicated by the Noble laureate Woodward, is presented with emphasis on hydroxy-isoporphyrins of tetra-aryl derivatives. The chemistry of metalloisoporphyrin has been discussed since the discovery of the first metallo isoporphyrin by Dolphin and co-workers, as no comprehensive article is available on this beautiful macrocycle. Attention is paid to the possible applications of metalloisoporphyrins as photosensitizers in photodynamic therapy, as a near infra red dye and as a reactive agent for different atom transfer reactions. Some important findings about reactivity and theoretical results of hydroxy isoporphyrins are discussed. Furthermore, the approaches of heme oxidation via isoporphyrin as an intermediate to understand the heme oxygenase mechanism are discussed. The metalloisoporphyrins are discussed reviewing coordination modes, structural changes, electronic properties and biological relevance. PMID- 26283519 TI - The Pathophysiological Mechanism Is an Independent Predictor of Long-Term Outcome in Stroke Patients with Large Vessel Atherosclerosis. AB - BACKGROUND: Etiopathological mechanisms underlying ischemic stroke play a crucial role in long-term prognosis. We aimed to investigate the association between the mechanism of stroke due to large vessel disease, and long-term outcome. METHODS: All consecutive patients registered in the Athens Stroke Registry with atherosclerotic stroke between 1993 and 2010 were included in the analysis. The patients were subdivided into 3 groups according to the presumed underlying mechanism: low-flow infarcts, artery-to-artery embolism, and intrinsic atherosclerosis. They were followed up for up to 10 years or until death. The end points of the study were 10-year all-cause mortality, stroke recurrence, and composite cardiovascular events. RESULTS: Five hundred two patients were classified as follows: 156 (31%) as low-flow (watershed) strokes, 256 (51%) as artery-to-artery embolic strokes, and 90 (18%) as intrinsic atherosclerotic strokes. The cumulative probability of 10-year mortality rate was similar between groups of patients with different stroke mechanisms: 49.9% (95% confidence interval [CI], 38.5-61.3) for patients with low-flow mechanism, 47.6% (95% CI, 39.4-55.8) for patients with artery-to-artery embolism, and 48.5% (95% CI, 34.0 63.0) for patients with intrinsic atherosclerosis. Patients in the intrinsic atherosclerosis group had significantly higher risks of recurrence (adjusted hazard ratio [HR] = 2.1; 95% CI, 1.19-3.73) compared with those in the artery-to artery embolism group. Moreover, patients in the intrinsic atherosclerosis and low-flow groups had significantly higher risks of composite cardiovascular events compared with those in the artery-to-artery embolism group (adjusted HR = 1.94; 95% CI, 1.26-3.00; and adjusted HR = 1.64; 95% CI, 1.13-2.38, respectively). CONCLUSION: Low-flow and intrinsic atherosclerosis strokes are associated with a high risk for future cardiovascular events and stroke recurrence. However, long term mortality is similar across different subgroups. PMID- 26283520 TI - Vasospastic Amaurosis Fugax Diagnosed by Cerebral Angiography. AB - We report a case of recurrent monocular blindness presumed to be caused by vasospasm, demonstrated by digital subtraction angiography. CASE REPORT: A 65 year-old man presented with recurrent visual loss in the left eye for 2 years. He had histories of hypertension, cigarette smoking, and May-Thurner syndrome. The symptom occurred variably from twice a day to once a week and usually lasted for 5 minutes. Brain magnetic resonance imaging, magnetic resonance angiography, and ophthalmologic evaluation did not reveal any abnormality. Cerebral digital subtraction angiography was performed. On the left internal carotid angiogram, vasospasm occurred in the cervical portion of the left internal carotid artery and, subsequently, the blood flow to the left ophthalmic artery diminished. This phenomenon was reproducible and, in the absence of vasospasm, the ophthalmic artery was well visualized with no steno-occlusive lesion. Examination of the carotid duplex showed diffuse luminal narrowing and increased flow velocities in the left cervical internal carotid artery without atherosclerotic plaque. Treatment was started with nimodipine, which markedly reduced the attacks. CONCLUSION: We assumed that vasomotor instability, which made the vessels vulnerable to spasm, may have caused a recurrent ocular symptom in our patient. PMID- 26283521 TI - Impact of Pulmonary Vein Isolation on Superior Vena Cava Potentials With a Second Generation Cryoballoon. AB - BACKGROUND: Radiofrequency ablation of the right superior pulmonary vein (RSPV) can lead to inadvertent superior vena cava (SVC) isolation due to the close anatomical proximity. This study aimed to evaluate the impact of PV isolation on SVC potentials with a second-generation cryoballoon. METHODS: Thirty-one consecutive paroxysmal atrial fibrillation patients who underwent PV isolation exclusively with a 28 mm second-generation cryoballoon and single 3-minute freeze technique were prospectively enrolled. The produced SVC potential conduction delay during the RSPV isolation was prospectively evaluated using circular mapping catheters placed in the SVC throughout the cryoballoon procedure. RESULTS: Stable SVC potentials were recorded in 28 (90.3%) patients. The produced SVC potential conduction delay during the RSPV isolation was a median of 6.0 (0.5 7.6) milliseconds, and >5.0 milliseconds in 16 (57.1%) patients. Among them, the delay had shortened by >5.0 milliseconds in 7 (43.8%) patients within 5 minutes after the RSPV application. The distance between the RSPV ostium and SVC was the sole parameter correlated with the produced delay (R = 0.77, P < 0.0001). For the association between the distance and a produced delay of >5 milliseconds, the area under the curve was 0.896 (95% confidential interval = 0.775-1.000). The optimal cutoff point for the distance predicting the occurrence of the conduction delay (>5 milliseconds) was 2.5 mm (sensitivity 83.3%, specificity 81.2%). CONCLUSIONS: RSPV isolation with a second-generation cryoballoon could produce an SVC potential conduction delay. The anatomical distance between the RSPV and SVC significantly correlated with the impact. PMID- 26283522 TI - Identifying patients infected with hepatitis B virus in sub-Saharan Africa: potential for misclassification. AB - Most research in sub-Saharan Africa establishes hepatitis B infection via one time hepatitis B surface antigen (HBsAg) testing. Of 237 HIV-infected patients from two clinical trials testing HBsAg positive (MiniVidas(r)), 206 (86.9%) had validated serological tests using another assay (Architect). Discrepancies could be due to inactive infection, highlighting the importance of assessing hepatitis B virus infection phase. PMID- 26283523 TI - Analytical performance of the automated multianalyte point-of-care mariPOC(r) for the detection of respiratory viruses. AB - The analytical performance of mariPOC(r) respi test (ArcDia(r) Laboratories, Turku, Finland) was evaluated using nucleic acid amplification techniques (NAATs) as the gold standard. The mariPOC assay allows automated detection of antigens from 8 respiratory viruses: influenza A and B viruses, respiratory syncytial virus, adenovirus, human metapneumovirus, and parainfluenza viruses 1-3. Positive results from samples with high viral load are available in 20min. Nasopharyngeal aspirates (n=192) from patients with acute respiratory infection and from previously positive samples were analyzed by mariPOC and NAATs (Simplexa(TM) FluA/FluB & RSV kit [n=118] and Luminex(r) Respiratory virus panel xTAG(r) RVP FAST [n=74]). Sensitivity, specificity, positive predictive value, and negative predictive value of mariPOC were 85.4%, 99.2%, 95.9%, and 97%, respectively, and 84.6% of positive results were reported in 20min. The good analytical performance and extended portfolio of mariPOC show this rapid assay as a good alternative for the etiological diagnosis of acute respiratory infection in laboratories that are not equipped with molecular assays. PMID- 26283524 TI - Anodal Direct Current Stimulation of the Cerebellum Reduces Cerebellar Brain Inhibition but Does Not Influence Afferent Input from the Hand or Face in Healthy Adults. AB - BACKGROUND: The cerebellum controls descending motor commands by outputs to primary motor cortex (M1) and the brainstem in response to sensory feedback. The cerebellum may also modulate afferent input en route to M1 and the brainstem. OBJECTIVE: The objective of this study is to determine if anodal transcranial direct current stimulation (tDCS) to the cerebellum influences cerebellar brain inhibition (CBI), short afferent inhibition (SAI) and trigeminal reflexes (TRs) in healthy adults. METHODS: Data from two studies evaluating effects of cerebellar anodal and sham tDCS are presented. The first study used a twin coil transcranial magnetic stimulation (TMS) protocol to investigate CBI and combined TMS and cutaneous stimulation of the digit to assess SAI. The second study evaluated effects on trigemino-cervical and trigemino-masseter reflexes using peripheral nerve stimulation of the face. RESULTS: Fourteen right-handed healthy adults participated in experiment 1. CBI was observed at baseline and was reduced by anodal cerebellar DCS only (P < 0.01). There was SAI at interstimulus intervals of 25 and 30 ms at baseline (both P < 0.0001), but cerebellar tDCS had no effect. Thirteen right-handed healthy adults participated in experiment 2. Inhibitory reflexes were evoked in the ipsilateral masseter and sternocleidomastoid muscles. There was no effect of cerebellar DCS on either reflex. CONCLUSIONS: Anodal DCS reduced CBI but did not change SAI or TRs in healthy adults. These results require confirmation in individuals with neurological impairment. PMID- 26283525 TI - Protein-kinase inhibitors: A new treatment pathway for autoimmune and inflammatory diseases? AB - Although advances in biological medicine have seen significant progress in the treatment of autoimmune and inflammatory disease, many patients do not experience a satisfactory response. Hence, there are two challenges facing the medical research community. The first is to continue development in the field of existing biological therapies, such as monoclonal antibodies. The second is to open new frontiers of research and explore treatment alternatives for non-responders to other therapies. Attention has increasingly turned to the therapeutic potential of small molecule weight kinase inhibitors (SMKIs), currently used extensively in oncology and haematology. Initial research into the therapeutic value of SMKIs for autoimmune and inflammatory diseases has been encouraging. SMKIs are taken orally, which reduces cost for the health provider, and could increase compliance for the patient. This is why research is now focusing increasingly on SMKIs as a new generation line of treatment in these diseases. Tofacitinib, an inhibitor of Janus-kinase, is currently the only drug approved for the treatment of rheumatoid arthritis by FDA. However, much more needs to be done to understand the intracellular signalling pathways and how these might affect disease progression before solid conclusions can be drawn. PMID- 26283526 TI - Developing a Novel Approach for Teaching Biopsychosocial Formulation. PMID- 26283527 TI - The Medical Education of Generation Y. PMID- 26283528 TI - Learning impairments identified early in life are predictive of future impairments associated with aging. AB - The Morris water maze (MWM) behavioral paradigm is commonly used to measure spatial learning and memory in rodents. It is widely accepted that performance in the MWM declines with age. However, young rats ubiquitously perform very well on established versions of the water maze, suggesting that more challenging tasks may be required to reveal subtle differences in young animals. Therefore, we have used a one-day water maze and novel object recognition to test whether more sensitive paradigms of memory in young animals could identify subtle cognitive impairments early in life that might become accentuated later with senescence. We have found that these two tasks reliably separate young rats into inferior and superior learners, are highly correlated, and that performance on these tasks early in life is predictive of performance at 12 months of age. Furthermore, we have found that repeated training in this task selectively improves the performance of inferior learners, suggesting that behavioral training from an early age may provide a buffer against age-related cognitive decline. PMID- 26283530 TI - Inflammatory Markers Change with Age, but do not Fall Beyond Reported Normal Ranges. AB - We examined the serum levels of IL-6, IL-8, TNF, IL-6R, TNF-R1, and CRP and the dynamics of changes in these levels according to age. The study included healthy individuals of 20-90 years of age. Participants were divided into subgroups based on their decade of life, and into subgroups of >=65 or <65 years. Serum cytokine levels were assayed by ELISA, and CRP using an immunoturbidimetric method. Serum CRP levels were within the normal range for all subgroups. The 60- to 70-year age group showed higher CRP than the 20- to 30- (p = 0.003), 30- to 40- (p = 0.009), and 40- to 50- (p = 0.030) year age groups. Serum cytokine levels were low. It was greater in the 60- to 70-year age group than in the 20- to 30- (p = 0.008) and 30- to 40- (p = 0.040) year groups, and was greater in the 70- to 90-year group than the 20- to 30-year group (p = 0.043). Serum TNF-R1 level in the 70- to 90-year group was greater than in all other age groups (p = 0.000 for all comparisons). Other measured parameters did not differ between groups. Serum levels of IL-6, CRP, and TNF-R1 were greater in participants >=65 than <65 years of age. Healthy older people showed low serum levels of CRP and pro-inflammatory cytokines, but higher than in younger population. Therefore, the adjustment of normal ranges in the elderly should be considered. Serum levels of pro inflammatory cytokines elevated beyond normal ranges indicate particular diseases. PMID- 26283529 TI - Effectiveness of a normative nutrition intervention (diet, physical activity and breastfeeding) on maternal nutrition and offspring growth: the Chilean maternal and infant nutrition cohort study (CHiMINCs). AB - BACKGROUND: Maternal obesity before and during pregnancy predicts maternal and infant risks of obesity and its associated metabolic conditions. Dietary and physical activity recommendations during pregnancy as well as weight monitoring are currently available in the Chilean primary health care system. However some of these recommendations are not updated and most of them are poorly implemented. We seek to assess the effectiveness of an intervention that enhances the implementation of updated nutrition health care standards (diet, physical activity, and breastfeeding promotion) during pregnancy on maternal weight gain and infant growth. METHODS: DESIGN & SETTING: Cluster randomized controlled trial. The cluster units will be 12 primary health care centers from two counties (La Florida and Puente Alto) from the South-East Area of Santiago randomly allocated to: 1) enhanced nutrition health care standards (intervention group) or 2) routine care (control group). PARTICIPANTS: Women seeking prenatal care before 15 weeks of gestation, residing within a catchment area of selected health centers, and who express that they are not planning to change residence will be invited to participate in the study. Pregnant women classified as high risk according to the Chilean norms (i.e age <16 or >40 years, multiple gestation, pre gestational medical conditions, previous pregnancy-related issues) and/or underweight will be excluded. INTERVENTION: Pregnant women who attend intervened health care centers starting at their first prenatal visit will receive advice regarding optimal weight gain during pregnancy and diet and physical activity counseling-support. Pregnant women who attend control health clinics will receive routine antenatal care according to national guidelines. We plan to recruit 200 women in each health center. Assuming a 20% loss to follow up, we expect to include 960 women per arm. MAIN OUTCOME MEASURES: 1) Achievement of adequate weight gain based on IOM 2009 recommendations and adequate glycaemic control at 24-28 weeks of pregnancy according to ADA 2011, and 2) healthy infant growth during the first year of age based on WHO standards. DISCUSSION: We expect that the intervention will benefit the participants in achieving adequate weight gain & metabolic control during pregnancy as well as adequate infant growth as a result of an increased impact of standard nutrition and health care practices. Gathered information should contribute to a better understanding of how to develop effective interventions to halt the maternal obesity epidemic and its associated co-morbidities in the Chilean population. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01916603. PMID- 26283531 TI - A simple and efficient method for imidazolinone herbicides determination in soil by ultra-high performance liquid chromatography-tandem mass spectrometry. AB - The use of pesticides in agriculture has generated numerous consequences to the environment, requiring analysis of the persistent residues in soil, water and air. The variability of soil properties interferes in the extraction of pesticide residues with robustness and accuracy. The group of imidazolinones herbicides, widely used for weed control, becomes an additional task in multiresidue extraction procedures because of their low pKa values. In order to determine these compounds in soil samples, different methods have been proposed, however they can be very laborious and require more time and well trained analysts. Thus, this study aimed to develop a simple and efficient method for determination of imidazolinones (imazamox, imazapic, imazapyr, imazaquin and imazethapyr) residues in soil, using an extraction with aqueous ammonium acetate solution (0.5 M) and clean-up with dispersive solid phase extraction employing PSA, followed by UHPLC MS/MS analysis. Satisfactory values of accuracy (70-93%) and RSD (<=17%) were achieved, as well as lower limit of quantification (5.0 MUg kg(-1)). Considering the matrix and compounds complexity, the developed and validated method proved to be an excellent tool for rapid analysis (20 min), with reliability for application in real samples with wide pH range. In the analysis of 22 real samples, the method allowed the quantification of imazapic (5.84 and 12.1 MUg kg( 1)), imazapyr (5.3 MUg kg(-1)) and imazethapyr (24.0 and 37.7 MUg kg(-1)) in three samples. PMID- 26283532 TI - A thin-layer chromatography-bioautographic method for detecting dipeptidyl peptidase IV inhibitors in plants. AB - A thin-layer chromatography (TLC)-bioautographic method was developed with the aim to detect dipeptidyl peptidase IV (DPP IV) inhibitors from plant extracts. The basic principle of the method is that the enzyme (DPP IV) hydrolyzes substrate (Gly-Pro-p-nitroaniline) into p-nitroaniline (pNA), which diazotizes with sodium nitrite, and then reacts with N-(1-naphthyl) ethylenediamine dihydrochloride in turn to form a rose-red azo dye which provides a rose-red background on the TLC plates. The DPP IV inhibitors showed white spots on the background as they blocked enzymolysis of the substrate to produce pNA. The method was validated with respect to selectivity, sensitivity, linearity, precision, recovery, and stability after optimizing key parameters including plate type, time and temperature of incubation, concentration of substrate, enzyme and derivatization reagents, and absorption wavelength. The results showed good lineary within amounts over 0.01-0.1MUg range for the positive control, diprotin A, with the coefficient of determination (r(2))=0.9668. The limits of detection (LOD) and quantification (LOQ) were 5 and 10ng, respectively. The recoveries ranged from 98.9% to 107.5%. The averages of the intra- and inter plate reproducibility were in the range of 4.1-9.7% and 7.6-14.7%, respectively. Among the nine methanolic extracts of medicinal herbs screened for DPP IV inhibitors by the newly developed method, Peganum nigellastrum Bunge was found to have one white active spot, which was then isolated and identified as harmine. By spectrophotometric method, harmine hydrochloride was found to have DPP-IV inhibitory activity of 32.4% at 10mM comparing to that of 54.8% at 50MUM for diprotin A. PMID- 26283533 TI - Rapid high performance liquid chromatography-high resolution mass spectrometry methodology for multiple prenol lipids analysis in zebrafish embryos. AB - The analysis of lipid molecules in living organism is an important step in deciphering metabolic pathways. Recently, the zebrafish has been adopted as a valuable animal model system to perform in vivo metabolomics studies, however limited methodologies and protocols are currently available to investigate zebrafish lipidome and even fewer to analyze specific classes of lipids. Here we present an HPLC-HRMS based method to rapidly measure multiple prenol lipid molecules from zebrafish tissues. In particular, we have optimized our method for concurrent detection of ubiquinones (Coenzyme Q6, Coenzyme Q9, Coenzyme Q10), cholesterol, vitamin E (alpha-tocopherol), vitamin K1 and vitamin K2. The purpose of this study was to compare different ionization modes, mobile phases and stationary phases in order to optimize lipid molecules separation. After HPLC HRMS parameters selection, several extraction conditions from zebrafish embryos were evaluated. We assessed our methodology by quantitation of analytical recovery on zebrafish extracts from wild-type or zebrafish mutants (barolo) affected by impaired biosynthesis of ubiquinones. PMID- 26283534 TI - Ageing, retirement and changes in vegetable consumption in France: findings from the prospective GAZEL cohort. AB - The aim of this study was to describe the change in vegetable consumption with ageing and the transition to retirement. Study subjects were the participants of the GAZEL prospective cohort (Gaz and Electricite de France) aged 40-49 years at inclusion in 1989 who retired between 1991 and 2008 (12,942 men and 2739 women). Four FFQ were completed from 1990 to 2009. We used multiple imputation by chained equations in order to avoid dropping incomplete cases. The OR for eating vegetables everyday was estimated as a function of ageing, retirement status and the place of lunch before retirement through generalised estimating equations. Analyses were stratified by sex, and models were adjusted for confounders, including current spousal status. In 1990, 17.7% of men and 31% of women reported eating vegetables daily. The odds of consuming vegetables everyday increased with ageing for both men and women. The usual place of lunch was home for less than half the sample before retirement and for almost every respondent after retirement. For those who changed their place of lunch, the association between being retired and the odds of eating vegetables daily was positive and significant. We found that, in this cohort, vegetable consumption increased with ageing. Retirement had an indirect effect on vegetable consumption mediated by changes in the place of lunch. PMID- 26283535 TI - Reply. PMID- 26283536 TI - Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus-infected macaques. AB - Innate lymphoid cells (ILCs) type 3, also known as lymphoid tissue inducer cells, plays a major role in both the development and remodeling of organized lymphoid tissues and the maintenance of adaptive immune responses. HIV/simian immunodeficiency virus (SIV) infection causes breakdown of intestinal barriers resulting in microbial translocation, leading to systemic immune activation and disease progression. However, the effects of HIV/SIV infection on ILC3 are unknown. Here, we analyzed ILC3 from mucosal and systemic lymphoid tissues in chronically SIV-infected macaques and uninfected controls. ILC3 cells were defined and identified in macaque lymphoid tissues as non-T, non-B (lineage negative), c-Kit(+)IL-7Ralpha(+) (CD117(+)CD127(+)) cells. These ILC3 cells highly expressed CD90 (~ 63%) and aryl hydrocarbon receptor and produced IL-17 (~ 63%), IL-22 (~ 36%), and TNF-alpha (~ 72%) but did not coexpress CD4 or NK cell markers. The intestinal ILC3 cell loss correlated with the reduction of total CD4(+) T cells and T helper (Th)17 and Th22 cells in the gut during SIV infection (P < 0.001). Notably, ILC3 could be induced to undergo apoptosis by microbial products through the TLR2 (lipoteichoic acid) and/or TLR4 (LPS) pathway. These findings indicated that persistent microbial translocation may result in loss of ILC3 in lymphoid tissues in SIV-infected macaques, further contributing to the HIV-induced impairment of gut-associated lymphoid tissue structure and function, especially in mucosal tissues. PMID- 26283537 TI - Prenatal exposure to bisphenol A disrupts mouse fetal lung development. AB - Developmental exposure to bisphenol A (BPA) is associated with lung dysfunction and diseases. However, it is unknown if this association has a fetal origin. The present study addressed this important question by examining the effects of BPA on fetal lung development. BPA was administered to pregnant mice via diet from embryonic day (E) 7.5 to E18.5. Fetal lungs were analyzed at E18.5 for changes in structure and expression of key molecular markers of lung maturation. Our main findings were as follows: BPA severely retards fetal lung maturation, as evidenced by diminished alveolar airspace (15% of control) and thickened septa, hallmarks of lung immaturity; this immaturity is characterized by aberrant alveolar epithelial type I cell differentiation because expression of the type I cell marker, aquaporin 5, but not type II cell markers, is dramatically reduced (16% of control); and the effects of BPA are likely mediated through the glucocorticoid signaling pathway because the expression of epithelial sodium channel gamma and glutathione peroxidase, 2 well-known glucocorticoid target genes, is down-regulated in BPA-exposed fetal lungs, and, importantly, maternal dexamethasone administration rescues the lung immaturity phenotype. Taken together, these findings demonstrate that BPA disrupts fetal lung maturation, thus suggesting a fetal origin for BPA-induced lung diseases. PMID- 26283538 TI - Where have all the mosquito nets gone? Spatial modelling reveals mosquito net distributions across Tanzania do not target optimal Anopheles mosquito habitats. AB - BACKGROUND: Malaria remains the deadliest vector-borne disease despite long-term, costly control efforts. The United Republic of Tanzania has implemented countrywide anti-malarial interventions over more than a decade, including national insecticide-treated net (ITN) rollouts and subsequent monitoring. While previous analyses have compared spatial variation in malaria endemicity with ITN distributions, no study has yet compared Anopheles habitat suitability to determine proper allocation of ITNs. This study assesses where mosquitoes were most likely to thrive before implementation of large-scale ITN interventions in Tanzania and determine if ITN distributions successfully targeted those areas. METHODS: Using Maxent, a species distribution model was constructed relating anopheline mosquito occurrences for 1999-2003 to high resolution environmental observations. A 2011-2012 layer of mosquito net ownership was created using georeferenced data across Tanzania from the Demographic and Health Surveys. The baseline mosquito habitat suitability was compared to subsequent ITN ownership using (1) the average ITN numbers per house and (2) the proportion of households with >=1 net to test whether national ITN ownership targets have been met and have tracked malaria risk. RESULTS: Elevation, land cover, and human population distribution outperformed variants of temperature and Normalized Difference Vegetation Index (NDVI) in anopheline distribution models. The spatial distribution of ITN ownership across Tanzania was near-random spatially (Moran's I = 0.07). Householders reported owning 2.488 ITNs on average and 93.41 % of households had >=1 ITN. Mosquito habitat suitability was statistically unrelated to reported ITN ownership and very weakly to the proportion of households with >=1 ITN (R(2) = 0.051). Proportional ITN ownership/household varied relative to mosquito habitat suitability (Levene's test F = 3.0037). Quantile regression was used to assess trends in ITN ownership among households with the highest and lowest 10 % of ITN ownership. ITN ownership declined significantly toward areas with the highest vector habitat suitability among households with lowest ITN ownership (t = -3.38). In areas with lowest habitat suitability, ITN ownership was consistently higher. CONCLUSIONS: Insecticide-treated net ownership is critical for malaria control. While Tanzania-wide efforts to distribute ITNs has reduced malaria impacts, gaps and variance in ITN ownership are unexpectedly large in areas where malaria risk is highest. Supplemental ITN distributions targeting prime Anopheles habitats are likely to have disproportionate human health benefits. PMID- 26283539 TI - Malaria vectors in South America: current and future scenarios. AB - BACKGROUND: Malaria remains a significant public health issue in South America. Future climate change may influence the distribution of the disease, which is dependent on the distribution of those Anopheles mosquitoes competent to transmit Plasmodium falciparum. Herein, predictive niche models of the habitat suitability for P. falciparum, the current primary vector Anopheles darlingi and nine other known and/or potential vector species of the Neotropical Albitarsis Complex, were used to document the current situation and project future scenarios under climate changes in South America in 2070. METHODS: To build each ecological niche model, we employed topography, climate and biome, and the currently defined distribution of P. falciparum, An. darlingi and nine species comprising the Albitarsis Complex in South America. Current and future (i.e., 2070) distributions were forecast by projecting the fitted ecological niche model onto the current environmental situation and two scenarios of simulated climate change. Statistical analyses were performed between the parasite and each vector in both the present and future scenarios to address potential vector roles in the dynamics of malaria transmission. RESULTS: Current distributions of malaria vector species were associated with that of P. falciparum, confirming their role in transmission, especially An. darlingi, An. marajoara and An. deaneorum. Projected climate changes included higher temperatures, lower water availability and biome modifications. Regardless of future scenarios considered, the geographic distribution of P. falciparum was exacerbated in 2070 South America, with the distribution of the pathogen covering 35-46% of the continent. As the current primary vector An. darlingi showed low tolerance for drier environments, the projected climate change would significantly reduce suitable habitat, impacting both its distribution and abundance. Conversely, climate generalist members of the Albitarsis Complex showed significant spatial and temporal expansion potential in 2070, and we conclude these species will become more important in the dynamics of malaria transmission in South America. CONCLUSIONS: Our data suggest that climate and landscape effects will elevate the importance of members of the Albitarsis Complex in malaria transmission in South America in 2070, highlighting the need for further studies addressing the bionomics, ecology and behaviours of the species comprising the Albitarsis Complex. PMID- 26283540 TI - Polycomb recruitment at the Class II transactivator gene. AB - The Class II Transactivator (CIITA) is the master regulator of Major Histocompatibility Class II (MHC II) genes. Transcription of CIITA through the IFN-gamma inducible CIITA promoter IV (CIITA pIV) during activation is characterized by a decrease in trimethylation of histone H3 lysine 27 (H3K27me3), catalyzed by the histone methyltransferase Enhancer of Zeste Homolog 2 (EZH2). While EZH2 is the known catalytic subunit of the Polycomb Repressive Complex 2 (PRC2) and is present at the inactive CIITA pIV, the mechanism of PRC2 recruitment to mammalian promoters remains unknown. Here we identify two DNA binding proteins, which interact with and regulate PRC2 recruitment to CIITA pIV. We demonstrate Yin Yang 1 (YY1) and Jumonji domain containing protein 2 (JARID2) are binding partners along with EZH2 in mammalian cells. Upon IFN-gamma stimulation, YY1 dissociates from CIITA pIV while JARID2 binding to CIITA pIV increases, suggesting novel roles for these proteins in regulating expression of CIITA pIV. Knockdown of YY1 and JARID2 yields decreased binding of EZH2 and H3K27me3 at CIITA pIV, suggesting important roles for YY1 and JARID2 at CIITA pIV. JARID2 knockdown also results in significantly elevated levels of CIITA mRNA upon IFN-gamma stimulation. This study is the first to identify novel roles of YY1 and JARID2 in the epigenetic regulation of the CIITA pIV by recruitment of PRC2. Our observations indicate the importance of JARID2 in CIITA pIV silencing, and also provide a novel YY1-JARID2-PRC2 regulatory complex as a possible explanation of differential PRC2 recruitment at inducible versus permanently silenced genes. PMID- 26283541 TI - Delivering health with integrity of purpose. PMID- 26283542 TI - Genome-wide identification and transcriptional analysis of folate metabolism related genes in maize kernels. AB - BACKGROUND: Maize is a major staple food crop globally and contains various concentrations of vitamins. Folates are essential water-soluble B-vitamins that play an important role as one-carbon (C1) donors and acceptors in organisms. To gain an understanding of folate metabolism in maize, we performed an intensive in silico analysis to screen for genes involved in folate metabolism using publicly available databases, followed by examination of the transcript expression patterns and profiling of the folate derivatives in the kernels of two maize inbred lines. RESULTS: A total of 36 candidate genes corresponding to 16 folate metabolism-related enzymes were identified. The maize genome contains all the enzymes required for folate and C1 metabolism, characterized by highly conserved functional domains across all the other species investigated. Phylogenetic analysis revealed that these enzymes in maize are conserved throughout evolution and have a high level of similarity with those in sorghum and millet. The LC-MS analyses of two maize inbred lines demonstrated that 5-methyltetrahydrofolate was the major form of folate derivative in young seeds, while 5 formyltetrahydrofolate in mature seeds. Most of the genes involved in folate and C1 metabolism exhibited similar transcriptional expression patterns between these two maize lines, with the highest transcript abundance detected on day after pollination (DAP) 6 and the decreased transcript abundance on DAP 12 and 18. Compared with the seeds on DAP 30, 5-methyltetrahydrofolate was decreased and 5 formyltetrahydrofolate was increased sharply in the mature dry seeds. CONCLUSIONS: The enzymes involved in folate and C1 metabolism are conserved between maize and other plant species. Folate and C1 metabolism is active in young developing maize seeds at transcriptional levels. PMID- 26283543 TI - Antioxidant potential, total phenolic and total flavonoid contents of Rhododendron anthopogonoides and its protective effect on hypoxia-induced injury in PC12 cells. AB - BACKGROUND: Rhododendron anthopogonoides Maxim, a kind of traditional Tibetan medicine, has been used to remove body heat, body detoxification, cough, asthma, stomachic and swelling, eliminate abundant phlegm and inflammatory for a long time. In the present study, the total phenols and total flavonoid contents as well as antioxidative properties of the crude extract and solvent fractions of R. anthopogonoides were determined using seven antioxidant assays. Additionally, the protective effect of the extracts on hypoxia-induced injury in PC12 cells was also investigated. METHODS: The content of total flavonoid and total phenolic was determined by the aluminum colorimetric method and Folin-Ciocalteu assay, respectively. In vitro antioxidant study, the effect of the crude extract and solvent fractions on total antioxidant activity, reducing power, DPPH radical scavenging, ABTS radical scavenging, superoxide radical scavenging, hydroxyl radical scavenging and nitric oxide radical scavenging were examined. The correlation between the phenolic and flavonoid content of the extracts and their antioxidant properties also analyzed. Furthermore, the protective effect of extracts on hypoxia-induced damage on PC12 cells was investigated by cell viability, lactate dehydrogenase (LDH) release, malondialdehyde (MDA) production and the activities of antioxidant enzymes. RESULTS: Our results showed that ethyl acetate and n-butanol fractions had higher content of phenolics and flavonoid compounds than other fractions. Except ABTS radical assay, n-butanol fraction exhibited the strongest antioxidant activity. While the hexane fraction showed the lowest antioxidant activity. Ethyl acetate also presented excellent antioxidant activity, which was just lower than n-butanol fraction. Significant correlation between the phenolic, flavonoid content of the extract and fractions with antioxidant assay excluding ABTS, OH scavenging assay was observed. Moreover, ethyl acetate and n-butanol fractions showed protective effect in PC12 cell under hypoxia condition, while crude extract and water fraction had no protective effect. In contrast, hexane fraction exhibited strong cytoprotective effect. Further study indicated that pretreatment of PC12 cells with ethyl acetate and n-butanol fractions, prior to hypoxia exposure, significantly increased the survival of cells and the activities of SOD, CAT, GSH-Px and T-AOC, as well as reduced the level of LDH and MDA. The gathered data demonstrated that ethyl acetate and n-butanol fractions were able to protect PC12 cells against hypoxia induced injury through direct free radical scavenging and modulation of endogenous antioxidant enzymes. CONCLUSION: These findings suggested that ethyl acetate and n-butanol fractions of R. anthopogonoides had significant antioxidant activity and could prevent PC12 cells against hypoxia-induced injury. So it might be regarded as an excellent source of antioxidants and had great potential to explore as therapeutic agent for preventing hypoxia related sickness in future. PMID- 26283544 TI - Effect of the JAK2/STAT3 inhibitor SAR317461 on human glioblastoma tumorspheres. AB - BACKGROUND: The STAT3 transcription factor is a major intracellular signaling protein and is frequently dysregulated in the most common and lethal brain malignancy in adults, glioblastoma multiforme (GBM). Activation of STAT3 in GBM correlates with malignancy and poor prognosis. The phosphorylating signal transducer JAK2 activates STAT3 in response to cytokines and growth factors. Currently there are no JAK-STAT pathway inhibitors in clinical trials for GBM, so we sought to examine the anti-GBM activity of SAR317461 (Sanofi-Aventis), a newer generation, highly potent JAK2 inhibitor that exhibits low toxicity and good pharmacokinetics. SAR317461 was initially approved for patient testing in the treatment of primary myelofibrosis (PMF), and has shown activity in preclinical models of melanoma and pulmonary cancer, but has not been tested in GBM. METHODS: We hypothesized that a potent small molecule JAK2 inhibitor could overcome the heterogeneous nature of GBM, and suppress a range of patient derived GBM tumorsphere lines and immortalized GBM cell lines. We treated with SAR317461 to determine IC50 values, and using Western blot analysis we asked whether the response was linked to STAT3 expression. Western blot analysis, FACS, and cell viability studies were used to identify the mechanism of SAR317461 induced cell death. RESULTS: We report for the first time that the JAK2 inhibitor SAR317461 clearly inhibited STAT3 phosphorylation and had substantial activity against cells (IC50 1-10 uM) from 6 of 7 different patient GSC derived GBM tumorsphere lines and three immortalized GBM lines. One patient GSC derived line did not constitutively express STAT3 and was more resistant to SAR317461 (IC50 ~25 uM). In terms of mechanism we found cleaved PARP and clear apoptosis following SAR317461. SAR317461 also induced autophagy and the addition of an autophagy inhibitor markedly enhanced cell killing by SAR317461. CONCLUSIONS: We conclude that SAR317461 potently inhibits STAT3 phosphorylation and that it has significant activity against those GBM cells which express activated STAT3. Further studies are warranted in terms of the potential of SAR317461 as single and combined therapy for selectively treating human patients afflicted with GBMs expressing activation of the JAK2-STAT3 signaling axis. PMID- 26283545 TI - Timing of antibiotics, volume, and vasoactive infusions in children with sepsis admitted to intensive care. AB - INTRODUCTION: Early administration of antibiotics for sepsis, and of fluid boluses and vasoactive agents for septic shock, is recommended. Evidence for this in children is limited. METHODS: The Alberta Sepsis Network prospectively enrolled eligible children admitted to the Pediatric Intensive Care Unit (PICU) with sepsis from 04/2012-10/2014. Demographics, severity of illness, and outcomes variables were prospectively entered into the ASN database after deferred consent. Timing of interventions were determined by retrospective chart review using a study manual and case-report-form. We aimed to determine the association of intervention timing and outcome in children with sepsis. Univariate (t-test and Fisher's Exact) and multiple linear regression statistics evaluated predictors of outcomes of PICU length of stay (LOS) and ventilation days. RESULTS: Seventy-nine children, age median 60 (IQR 22-133) months, 40 (51%) female, 39 (49%) with severe underlying co-morbidity, 44 (56%) with septic shock, and median PRISM-III 10.5 [IQR 6.0-17.0] were enrolled. Most patients presented in an ED: 36 (46%) at an outlying hospital ED, and 21 (27%) at the Children's Hospital ED. Most infections were pneumonia with/without empyema (42, 53%), meningitis (11, 14%), or bacteremia (10, 13%). The time from presentation to acceptable antibiotic administration was a median of 115.0 [IQR 59.0-323.0] minutes; 20 (25%) of patients received their antibiotics in the first hour from presentation. Independent predictors of PICU LOS were PRISM-III, and severe underlying co-morbidity, but not time to antibiotics. In the septic shock subgroup, the volume of fluid boluses given in the first 2 hours was independently associated with longer PICU LOS (effect size 0.22 days; 95% CI 0.5, 0.38; per ml/kg). Independent predictors of ventilator days were PRISM-III score and severe underlying co-morbidity. In the septic shock subgroup, volume of fluid boluses in the first 2 hours was independently associated with more ventilator days (effect size 0.09 days; 95% CI 0.02, 0.15; per ml/kg). CONCLUSION: Higher volume of early fluid boluses in children with sepsis and septic shock was independently associated with longer PICU LOS and ventilator days. More study on the benefits and harms of fluid bolus therapy in children are needed. PMID- 26283546 TI - Akt activation increases cellular cholesterol by promoting the proteasomal degradation of Niemann-Pick C1. AB - Null mutations of the Niemann-Pick type C1 (NPC1) gene cause NPC disease, a lysosomal storage disorder characterized by cholesterol accumulation in late endosomes (LE) and lysosomes (Ly). Nascent or mutated NPC1 is degraded through the ubiquitin-proteasome pathway, but how NPC1 degradation is regulated remains currently unknown. In the present study, we demonstrated a link between NPC1 degradation and the Akt (protein kinase B)/mTOR [mammalian (or mechanistic) target of rapamycin] signalling pathway in cervical cancer cell lines. We provided evidence that activated Akt/mTOR pathway increased NPC1 degradation by ~50% in C33A cells when compared with SiHa or HeLa cells. NPC1 degradation in C33A cells was reversed when Akt/mTOR activation was blocked by specific inhibitors or when mTORC1 (mTOR complex 1) was disrupted by regulatory associated protein of mTOR (Raptor) knockdown. Importantly, inhibition of the Akt/mTOR pathway led to decreased NPC1 ubiquitination in C33A cells, pointing to a role of Akt/mTOR in the proteasomal degradation of NPC1. Moreover, we found that NPC1 depletion in several cancer cell lines inhibited cell proliferation and migration. Our results uncover Akt as a key regulator of NPC1 degradation and link NPC1 to cancer cell proliferation and migration. PMID- 26283547 TI - Necroptosis signalling is tuned by phosphorylation of MLKL residues outside the pseudokinase domain activation loop. AB - The pseudokinase MLKL (mixed lineage kinase domain-like), has recently emerged as a critical component of the necroptosis cell death pathway. Although it is clear that phosphorylation of the activation loop in the MLKL pseudokinase domain by the upstream protein kinase RIPK3 (receptor-interacting protein kinase-3), is crucial to trigger MLKL activation, it has remained unclear whether other phosphorylation events modulate MLKL function. By reconstituting Mlkl(-/-), Ripk3(-/-) and Mlkl(-/-)Ripk3(-/-) cells with MLKL phospho-site mutants, we compared the function of known MLKL phosphorylation sites in regulating necroptosis with three phospho-sites that we identified by MS, Ser(158), Ser(228) and Ser(248). Expression of a phosphomimetic S345D MLKL activation loop mutant induced stimulus-independent cell death in all knockout cells, demonstrating that RIPK3 phosphorylation of the activation loop of MLKL is sufficient to induce cell death. Cell death was also induced by S228A, S228E and S158A MLKL mutants in the absence of death stimuli, but was most profound in Mlkl(-/-)Ripk3(-/-) double knockout fibroblasts. These data reveal a potential role for RIPK3 as a suppressor of MLKL activation and indicate that phosphorylation can fine-tune the ability of MLKL to induce necroptosis. PMID- 26283548 TI - Transient limb ischaemia during extracorporeal membrane oxygenation: inappropriate venous cannula location. AB - Percutaneous placement of extracorporeal membrane oxygenation (ECMO) cannulas has many benefits. However, limb ischaemia still remains as an unresolved problem. We experienced an interesting case of limb ischaemia that was caused by external compression of the superficial femoral artery by the venous cannula. A 73-year old woman underwent veno-arterial ECMO due to sudden cardiac arrest with percutaneous femoral cannulations at the right common femoral vein and the left common femoral artery. Three hours after cannulation, the patient's right lower extremity was cool and pale, and the arterial pulses of dorsalis pedis artery and posterior tibial artery were not palpable. After confirming the absence of blood flow at the peripheral arteries of the lower extremity through colour Doppler ultrasonography, we explored the right femoral cannulation area. The venous cannula, which was approaching the common femoral vein from the lateral side, was passing between the bifurcation area of the superficial and deep femoral arteries, directly compressing the superficial femoral artery from beneath. We rapidly removed the inappropriately placed venous cannula, and then re-inserted it at another location of the femoral vein. Although it was an unusual case where arterial occlusion was due to external compression of the venous cannula, successful limb reperfusion could be obtained through rapid identification and correction. PMID- 26283549 TI - Outcomes after early or late timing of surgery for infective endocarditis with ischaemic stroke: a retrospective cohort study. AB - OBJECTIVES: The timing of cardiac surgery for infective endocarditis with ischaemic stroke remains controversial. METHODS: Using a nationwide inpatient database in Japan, we conducted a retrospective observational study. We identified patients aged 20 years or older with ischaemic stroke on admission who were diagnosed with infective endocarditis and underwent cardiac surgery during the initial hospitalization between July 2010 and March 2013. In-hospital mortality and perioperative complications were compared between the early (<=7 days) and late (>7 days) surgery groups using logistic regression analyses with adjustment for propensity scores and inverse probability of treatment weighting. RESULTS: We identified 253 patients who underwent cardiac valve surgery for infective endocarditis with ischaemic stroke on admission. In-hospital mortality rates were 8.6 and 9.5% in the early (n = 105) and late (n = 148) surgery groups, respectively. There were no significant differences in the in-hospital mortality between the early and late surgery groups in the propensity score-adjusted model [odds ratio (OR), 0.95; 95% confidence interval (CI), 0.35-2.54] and inverse probability-weighted model (risk difference, -0.82%; 95% CI, -6.43 to 4.84%). The perioperative complication rates were 42.9 and 37.8% in the early and late surgery groups, respectively, and showed no significant differences in the propensity score-adjusted model (OR, 1.11; 95% CI, 0.63-1.97) and inverse probability-weighted model (risk difference, 1.54%; 95% CI, -7.13 to 10.2%). CONCLUSIONS: Early timing of surgery for infective endocarditis patients with ischaemic stroke was not associated with higher in-hospital mortality or complications after admission. Early timing of surgery may not be contraindicated for infective endocarditis patients with ischaemic stroke. PMID- 26283550 TI - Distribution of human papillomavirus (HPV) genotypes and bacterial vaginosis presence in cervical samples from Paraguayan indigenous. AB - OBJECTIVE: To determine the frequency of human papillomavirus (HPV) types and to assess bacterial vaginosis (BV) possible associations with cervical infections in indigenous Paraguayan women of the Department of Presidente Hayes. METHODS: This study included 181 sexually active women without cervical lesions. HPV typing was performed by polymerase chain reaction with primers PGMY 09/11 followed by reverse line hybridization. BV was diagnosed by the Nugent criteria using the results from a Gram stain smear. RESULTS: Sixteen percent of women were positive for at least one high risk HPV type (HR-HPV). The most frequent genotypes were HPV 16 (4.4%), followed by HPV 58 (3.3%), HPV 45 (3.3%), HPV 53 (2.8%) and HPV 11 (2.8%). A significant association between HR-HPV and BV was observed (p=0.01). In addition, women with BV had a higher frequency of Chlamydia trachomatis (p=0.0007), Trichomonas vaginalis (p=0.00009), Mycoplasma hominis (p=0.001). CONCLUSIONS: A large variety of HPV genotypes was detected and showed a slightly different pattern from previous studies on urban women in Paraguay, with the predominance of HR-HPV. Furthermore, the information of co-infections involved in BV could be useful for the improvement of national prevention programs, as well as for laboratory surveillance of these genital infections. PMID- 26283551 TI - Efficacy and safety of tigecycline for the treatment of severe infectious diseases: an updated meta-analysis of RCTs. AB - OBJECTIVES: To assess the efficacy and safety of tigecycline in comparison with other antimicrobial treatments for infectious diseases. DESIGN: Databases of PubMed, Embase and the Cochrane Library were searched through Feb. 2015. The reference lists of the initially identified articles and systemic review articles were manually searched. Randomized controlled trials assessing tigecycline and other antibiotics for infectious diseases in adult patients were included. RESULTS: Fifteen RCTs including 7689 cases were identified. We found that tigecycline was not as effective as the comparator agents for clinical treatment success (for the clinically evaluable population, odds ratio [OR] = 0.83, 95% confidence interval [CI] = (0.73, 0.96), P=0.01; for the clinically modified intent-to-treat (mITT) population, OR = 0.81, 95% CI = (0.72, 0.92), P=0.001). There was no significant difference in microbiological treatment success with lower eradication rate in tigecycline versus comparators (for the microbiologically evaluable population, OR = 0.94, 95% CI = (0.77, 1.16), P=0.56; for the microbiological mITT populations, OR = 0.91, 95% CI = (0.74, 1.11), P=0.35). Adverse events and all-cause mortality were more common in the tigecycline group. CONCLUSIONS: Tigecycline is not as effective as other antibiotics with relatively more frequency of adverse events and higher mortality rate. PMID- 26283552 TI - Detection and circulation of hepatitis B virus immune escape mutants among asymptomatic community dwellers in Ibadan, southwestern Nigeria. AB - BACKGROUND: In 2012, the first Nigerian Hepatitis B Virus (HBV) immune escape mutant (IEM) case was detected in a pregnant woman in southwestern Nigeria. Consequently, this study was designed to investigate the presence and possible circulation of IEMs amongst asymptomatic community dwellers in southwestern Nigeria. METHODS: Blood specimens collected from 438 asymptomatic community dwellers were screened for HBsAg using ELISA technique. Subsequently, the S-gene was amplified in HBsAg positive samples by a nested PCR protocol, and amplicons sequenced. Isolates were then subtyped by amino acid residues at positions 122, 127, 134 and 160, and genotyped by phylogenetic analysis. RESULTS: Of the 31 (7.08%) samples positive for HBsAg, the ~ 408 bp Sgene fragment was successfully amplified and sequenced in 27. Samples obtained from 4 patients could not be amplified due to low titres. Sequence data from only 15 of the isolates could be analysed further as eight of the remaining 12 had multiple peaks while the rest three showed no similarity to any HBV gene when subjected to BLAST analysis. Thirteen of the 15 isolates were identified as genotype E. Eleven of which were subtyped as ayw4 while the remaining two could not be subtyped due to sR122Q/P substitutions. The last two isolates that could not be genotyped and subtyped had other mutations in the "a" determinant associated with IEMs. CONCLUSIONS: This study confirmed presence and circulation of HBV IEM in Nigeria, the country's inclusion in the genotype E crescent, and the value of phylogenetic analysis in HBV identification. PMID- 26283554 TI - History of the Buttonhole Technique. AB - The constant side method of access cannulation in hemodialysis, popularly known as the 'buttonhole' method, has an interesting history. Dr. Zbylut J. Twardowski, a Polish nephrologist, discovered this technique by pure serendipity in 1972. A patient with a complicated vascular access history and limited options for cannulation was repeatedly 'stuck' at the same sites by a nurse. Soon it was noticed that the cannulation at the same spot became easier with time. Since the needles were being reused, the sharpness of the needles decreased with time and the bluntness of the needle seemed to minimize the damage to the cannulation tract (another serendipity!). This method soon became popular among patients, and many patients started using this technique. This chapter traces the invention of this technique and its subsequent development following Dr. Twardowski's emigration to the USA. PMID- 26283553 TI - Cholera in pregnancy: Clinical and immunological aspects. AB - BACKGROUND: The objective of this study was to examine the clinical and immunological features of cholera in pregnancy. METHODS: Women of reproductive age presenting to the icddr,b Dhaka hospital with cholera, and enrolled as part of a larger cohort study, were tested for pregnancy on admission. We compared initial clinical features and immune responses of pregnant patients with non pregnant female patients at days 2, 7 and 21 after infection. RESULTS: Among reproductive age women enrolled between January 2001 and May 2006, 9.7% (14/144) were pregnant. The duration of diarrhoea prior to admission tended to be higher in pregnant compared to non-pregnant patients (p=0.08), but other clinical characteristics did not differ. Antibody responses to cholera toxin B subunit (CtxB), toxin-coregulated pilus A (TcpA), Vibrio cholerae lipopolysaccharide (LPS), and serum vibriocidal antibody responses, were comparable between pregnant and non-pregnant patients. There were no deaths among the pregnant cases or non pregnant controls, and no adverse foetal outcomes, including stillbirths, during 21 days of follow up of pregnant cases. CONCLUSIONS: To our knowledge, this is the first report of immune responses in pregnant women with cholera. We found that pregnant woman early in pregnancy has comparable clinical illness and subsequent immune responses compared to non-pregnant women. These findings suggest that the evaluation of safety and immunogenicity of oral cholera vaccines in pregnancy should be an area of future investigations. PMID- 26283556 TI - Buttonhole Tunnel Tract Creation with the BioHole(r) Buttonhole Device. AB - BACKGROUND: Cannulation, and in particular, skilled cannulation is the cornerstone to preserving the arteriovenous fistula, the lifeline for a patient receiving long-term hemodialysis therapy. The buttonhole cannulation method has seen a huge revival in the 2000s, but it can sometimes prove challenging to implement successfully. This chapter discusses and describes the method of creating a buttonhole tract using the BioHole(r) device (a sterile polycarbonate peg), and describes the associated advantages and disadvantages. In a busy hemodialysis unit, use of the thumbtack-shaped 5-mm peg allows a fixed puncture route to be created quickly in just 7-14 days. The peg is placed at the site where the sharp puncture needle has just been removed by the designated primary cannulator. The peg remains in place until the next dialysis session when it is removed, the dialysis therapy completed as usual, and a new peg is inserted after hemostasis has been achieved. These steps are repeated for 1-2 weeks. Once the tunnel is formed, use of the peg is no longer needed and a blunt-ended puncture needle is inserted along the track each time. Buttonhole cannulation using the BioHole peg device offers advantages including reduced risk of needling complications and arteriovenous fistula failure, speedy transition to blunt needles, the tunnel track remaining narrow thus reducing the risk of developing an exit site infection, and suitability in difficult sites. Possible disadvantages are increased cost for purchase of the pegs during the track break in period and potential complications such as discomfort, bleeding, and risk of infection. These risks/disadvantages minimize after the transition to blunt needles which in itself is a safer option than using sharp needles. As supported by KDOQI (2006) and the UK Renal Association (2011), adoption of the buttonhole method as the cannulation technique of choice is recommended in the majority of patients undergoing hemodialysis who have a native fistula. PMID- 26283555 TI - The Impact of Buttonhole Cannulation on Patients and Staff in Hemodialysis Facilities. AB - The two reasons that patients desire buttonhole cannulation are avoidance of puncture pain and extension of arteriovenous fistula life. Despite the desire to receive buttonhole cannulation by many patients, medical staff at most local hemodialysis facilities tend to hesitate to implement the cannulation method. This method is used on patients in the dialysis unit at Saitama Medical Center, but tends to be discontinued for those patients upon their transfer to local hemodialysis facilities. Medical staff members of one local hemodialysis facility report the percentage of patients on the buttonhole method was 53% in 2007, but that it sharply decreased to 17% in 2013. Hesitation by local hemodialysis facilities to adopt the buttonhole method is due to, but not limited to, several factors. These factors include the frequently occurring trampoline effect, the difficulty of removing scabs, formation of a false buttonhole track, and the pain from insertion of a dull needle. Perceived differences in the value of buttonhole cannulation may potentially affect communication between patients and staff in local hemodialysis facilities. PMID- 26283557 TI - Causes and Solutions of the Trampoline Effect. AB - A trampoline effect may occur mainly when a buttonhole tract and the vessel flap fail to form a straight line. Certain findings, however, suggest another cause is when the vessel flap is too small. The frequency of the trampoline effect, for example, is lower when a buttonhole tract is created by multiple punctures of the arteriovenous fistula (AVF) vessel than when it is done by one-time puncture of the vessel. Lower frequency of the trampoline effect with multiple punctures of the AVF vessel may be due to enlargement of the initial puncture hole on the vessel every time the vessel is punctured with a sharp needle. Even if aiming at exactly the same point on the AVF vessel every time, the actual puncture point shifts slightly at every puncture, which potentially results in enlargement of the initial hole on the AVF vessel. Moreover, in some patients, continued use of a buttonhole tract for an extended period of time increases the frequency of the trampoline effect. In such cases, reduction of the incidence of the trampoline effect can be achieved by one buttonhole cannulation using a new dull needle with sharp side edges that is used to enlarge the vessel flap. Such single buttonhole cannulation may suggest that the increased frequency of the trampoline effect also potentially occurs in association with gradually diminishing flap size. As a final observation, dull needle insertion into a vessel flap in the reverse direction has been more smoothly achieved than insertion into a vessel flap in the conventional direction. A vessel flap in the reverse direction can be adopted clinically. PMID- 26283558 TI - A New Method That Enables Complete Removal of Scabs at Buttonhole Entry Sites. AB - BACKGROUND: Scab removal is a time-consuming process and often injures the skin at a buttonhole entry site. Incomplete removal of scabs may cause access-related infection. METHODS: In a new procedure, buttonhole entry sites were treated with a moist healing step after hemodialysis, and then a formed scab was wiped off with a microfiber towel during bathing on the night prior to hemodialysis, which was performed on the following day. In the moist healing step, the entry site was disinfected with a diluted povidone-iodine solution (0.1% povidone-iodine solution). RESULTS: When the buttonhole entry sites of the patients were treated with the new procedure, the scabs had already been removed at the buttonhole entry sites, and the sites were covered with a thin transparent membrane. Histological examination showed the thin membrane was stratum corneum, in which nuclei are still seen in keratinocytes. CONCLUSION: By treating the buttonhole entry sites of patients with the wound moist healing method and then rubbing the sites with a microfiber towel during bathing, scabs can be removed without injuring the skin at the sites in advance. PMID- 26283560 TI - Relationship between Years Elapsed after Initial Buttonhole Cannulation and Frequency of Vascular Access-Related Infections. AB - BACKGROUND: A reason for the higher frequency of vascular access-related infections in buttonhole cannulation patients remains to be elucidated. If the higher frequency of infections is associated with a factor(s) inherent to the buttonhole method (e.g. existence of a buttonhole track or other factors), the frequency of such infections is expected to increase upon starting buttonhole cannulation. On the other hand, if the higher frequency of the infections is associated with a factor(s) developing secondarily while performing buttonhole cannulation for months or years (e.g. deformity of the buttonhole entry site or other factors), the frequency is expected to rise after a certain time elapses from initiation of buttonhole cannulation. In case the higher frequency of the infections is associated with a factor(s) developing secondarily, the problem may potentially be solved. Thus, the present study is to clarify whether there is 'an infection calm period' after buttonhole cannulation is started. METHODS: The relationship between the time (in years) after buttonhole cannulation is started and frequency of vascular access-related infections was investigated. RESULTS: Frequency of access-related infections was almost constant for 6 years after buttonhole cannulation was started. At the sixth year from initiation of buttonhole cannulation, however, the frequency of access-related infections started rising. CONCLUSION: The rise in frequency of vascular access-related infections in buttonhole cannulation may not be directly associated with inherent factor(s) of the method, but rather a factor(s) developing secondarily while performing buttonhole cannulation over a period of years. PMID- 26283559 TI - Deformity of Buttonhole Entry Site Causes Higher Frequency of Vascular Access Related Infection. AB - BACKGROUND: Vascular access-related infection is more frequent in patients using the buttonhole method for cannulation of the arteriovenous access for hemodialysis. Deformity of buttonhole entry sites is frequently observed among patients on the buttonhole method for extended periods of time. With deformed buttonhole entry sites, moreover, scabs are often incompletely removed at the time of buttonhole cannulation. METHOD: In 166 patients using the buttonhole method at Hino Clinic in Osaka, Japan as of June 30, 2014, the shapes of buttonhole entry sites were categorized into the following 3 types: flat, depressive deformity, and bulging deformity. A multivariate logistic regression method was used to analyze associations between various data including shapes of buttonhole entry sites and occurrence of access-related infection. We also examined microscopic features of the buttonhole entry site tissue that was removed from a patient who died after 3 years of buttonhole cannulation. RESULTS: For the flat buttonhole entry sites, frequency of access-related infection was 0.12 events/1,000 arteriovenous fistulas as compared to 0.47 events/1,000 arteriovenous fistulas for the entry sites with bulging deformity. Such infection did not occur for the entry sites with depressive deformity. The multivariate logistic regression analysis revealed a significant association between an entry site with bulging deformity and occurrence of access-related infection (odds ratio = 5.369, p = 0.0085). Furthermore, the microscopic section showed granulations beneath the skin at the buttonhole entry site and around the buttonhole tract. CONCLUSION: A significant association was shown between an entry site with bulging deformity and occurrence of access-related infection. The microscopic features of the buttonhole entry site of the patient on the buttonhole method for 3 years suggest that the entity of bulging deformity at the entry site is hypertrophic granulation. PMID- 26283561 TI - Long-Term Safety of Buttonhole Cannulation and Efficacy of Mupirocin Prophylaxis. AB - Buttonhole cannulation has drawn considerable interest in recent years, particularly with the proliferation of home hemodialysis. Touted benefits of this cannulation method include reduced pain, ease of use, reduced aneurysm formation, and overall greater patient satisfaction. However, recent studies have also suggested that systemic and local infection rates are higher with buttonhole cannulation compared with the standard rope-ladder method. In this review, we summarize recent systematic review findings and practice guidelines addressing the benefits and harms of buttonhole cannulation, and discuss the role of topical antimicrobial prophylaxis. PMID- 26283562 TI - Application of Buttonhole Cannulation Technique to Surgically Superficialized Arteries. AB - In Japan, use of a surgically superficialized brachial artery is recommended for vascular access in patients who are either unable to tolerate hemodialysis because of reduced cardiac function or who do not have vessels suitable for creation of an arteriovenous fistula. Superficializing a brachial artery involves relocating a portion of the artery into subcutaneous tissue and immobilizing the artery at that location. Superficialized artery access can result in certain serious complications, such as an aneurysm and/or stenosis. In order to avoid such complications, we attempted applying the buttonhole method to this vascular access. A buttonhole track was created slightly distal from the center of the superficialized portion of a brachial artery approximately 2 weeks after superficialization. When arteriosclerosis was evident in that location, we tried to find a less sclerotic portion, under ultrasonography guidance, for creation of the arterial-side buttonhole track. For returning extracorporeal circulated blood, a normal vein on the arm with a superficialized brachial artery was cannulated with a sharp needle. Recently, however, we attempted to create a buttonhole track also on a vein for venous-side buttonhole cannulation. The brachial artery was superficialized in 5 patients. In all patients, buttonhole cannulation was successfully performed with the artery access. Buttonhole cannulation had been performed on these patients for 8-54 months. No serious complications such as a pseudoaneurysm were found in these patients. Serious complications specific to the superficialized artery access may be prevented by application of the buttonhole method. PMID- 26283563 TI - Canine sterile nodular panniculitis: a retrospective study of 39 dogs. AB - BACKGROUND: Canine sterile nodular panniculitis (SNP) is an inflammatory disease of the panniculus that is typically managed with immunomodulatory or immunosuppressive treatments. It has been reported to be a cutaneous marker of an underlying systemic disease. HYPOTHESIS/OBJECTIVES: To assess the presence or absence of concurrent systemic diseases associated with canine SNP and to document breed predispositions. ANIMALS: Thirty nine dogs presented to a veterinary teaching hospital from 1990 to 2012 which met inclusion criteria. METHODS: Inclusion in this retrospective study required a diagnosis of SNP via histopathological analysis and negative special stains for infectious organisms. Breed distributions of affected dogs were compared to all other dogs examined at this hospital during the study period. Correlations between the histological pattern of panniculitis and the histological presence of dermatitis, clinical presentation of lesions, dog breed and therapeutic outcomes were assessed. RESULTS: Australian shepherd dogs, Brittany spaniels, Dalmatians, Pomeranians and Chihuahuas were significantly over-represented, but correlations between inflammatory patterns of panniculitis and other histological and clinical factors were not identified. Based on the information available in medical records, 32 dogs (82.1%) had no concurrent systemic diseases identified. Four dogs had concurrent polyarthritis, which may be related to SNP through unknown mechanisms. CONCLUSIONS/CLINICAL IMPORTANCE: This study identified several novel breed predilections for SNP; it failed to find any clear correlations with associated systemic diseases other than polyarthritis. The histological inflammatory pattern of SNP does not predict therapeutic outcome. PMID- 26283564 TI - Diverticulitis in HIV-infected patients within the United States. AB - OBJECTIVES: Diverticulitis in patients on immunosuppressant therapy has been associated with increased mortality, but there are no data for HIV-infected patients. Our aim was to compare the outcomes of hospitalizations for diverticulitis in patients with and without HIV infection. METHODS: Cross sectional study of hospitalizations in the United States accessed through the Nationwide Inpatient Sample, Healthcare Cost and Utilization Project. Patients hospitalized for diverticulitis in 2007-2011 were included in the analysis. The primary outcomes of interest were mortality and surgical therapy rates. Patients from 2003 to 2011 were utilized to analyse trends in prevalence. RESULTS: There were 2375 patients with HIV infection hospitalized for diverticulitis and 1 160 391 patients without HIV infection hospitalized for diverticulitis from 2007 to 2011. The patients with HIV infection were younger and more likely to be male and nonwhite (P < 0.001 for all). There were also differences in insurance types (P < 0.001) and hospitals [size (P = 0.008), type (P < 0.001) and location (P < 0.001)]. After multivariate analysis, patients with diverticulitis and HIV infection had a significantly increased in-hospital mortality rate [odds ratio (OR) 3.94 (95% confidence interval, CI, 1.52-10.20)] and a lower rate of surgical intervention [OR 0.74 (95% CI 0.57-0.95)]. From 2003 to 2011, there was a linear increasing trend in the prevalence of HIV infection among patients hospitalized for diverticulitis (P < 0.001). CONCLUSIONS: HIV-infected patients with diverticulitis had increased mortality and received less surgical treatment in comparison to the general population. Diverticulitis in HIV-infected patients increased in prevalence over the study period. PMID- 26283565 TI - Intramuscular myxoma on the forehead: An unusual localization with useful sonographic findings. PMID- 26283566 TI - Standardizing Outcome Reporting in Bariatric/Metabolic Surgery. PMID- 26283567 TI - Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial. AB - In patients with relapsed or refractory (r/r) acute myeloid leukemia (AML), long term disease control can only be achieved by allogeneic hematopoietic stem cell transplantation (HSCT). We studied the safety and efficacy of clofarabine-based salvage therapy. The study was designed as phase II, multicenter, intent-to transplant (ITT) study. A total of 84 patients with r/r AML were enrolled. All patients received at least one cycle of CLARA (clofarabine 30 mg/m(2) and cytarabine 1 g/m(2), days 1-5). Chemo-responsive patients with a donor received HSCT in aplasia after first CLARA. Generally, HSCT was performed as soon as possible. The conditioning regimen consisted of clofarabine (4 * 30 mg/m(2)) and melphalan (140 mg/m(2)). The median patient age was 61 years (range 40-75). On day 15 after start of CLARA, 26% of patients were in a morphologically leukemia free state and 79% exposed a reduction in bone marrow blasts. Overall, 67% of the patients received HSCT within the trial. The primary end point, defined as complete remission after HSCT, was achieved by 60% of the patients. According to the ITT, overall survival at 2 years was 43% (95% confidence interval (CI), 32 54%). The 2-year disease-free survival for transplanted patients was 52% (95% CI, 40-69%). Clofarabine-based salvage therapy combined with allogeneic HSCT in aplasia shows promising results in patients with r/r AML. PMID- 26283568 TI - Preparative isolation of polymerase chain reaction products using mixed-mode chromatography. AB - The polymerase chain reaction (PCR) has become one of the most useful techniques in molecular biology laboratories around the world. The purification of the target DNA product is often challenging, however, and most users are restricted to employing available commercial kits. The recent developments in mixed-mode chromatography have shown higher selectivity for a variety of nucleic acid containing samples. Capto Adhere is a mixed-mode chromatography resin that offers a high-selectivity ligand and is here applied for the purification of amplified DNAs from PCR mixtures in a 10-min single step, with yields above 95%, high linearity, and high precision for different concentrations. PMID- 26283569 TI - Influenza-associated mortality in Thailand, 2006-2011. AB - BACKGROUND: Influenza-associated mortality in subtropical or tropical regions, particularly in developing countries, remains poorly quantified and often underestimated. We analyzed data in Thailand, a middle-income tropical country with good vital statistics and influenza surveillance data. METHODS: We obtained weekly mortality data for all-cause and three underlying causes of death (circulatory and respiratory diseases, and pneumonia and influenza), and weekly influenza virus data, from 2006 to 2011. A negative binomial regression model was used to estimate deaths attributable to influenza in two age groups (<65 and >=65 years) by incorporating influenza viral data as covariates in the model. RESULTS: From 2006 to 2011, the average annual influenza-associated mortality per 100 000 persons was 4.0 (95% CI: -18 to 26). Eighty-three percent of influenza-associated deaths occurred among persons aged > 65 years. The average annual rate of influenza-associated deaths was 0.7 (95% CI: -8.2 to 10) per 100 000 population for person aged <65 years and 42 (95% CI: -137 to 216) for person aged >= 65 years. DISCUSSION: In Thailand, estimated excess mortality associated with influenza was considerable even during non-pandemic years. These data provide support for Thailand's seasonal influenza vaccination campaign. Continued monitoring of mortality data is important to assess impact. PMID- 26283570 TI - Understanding snacking through a practice theory lens. AB - This article approaches snacking from a practice theory perspective in order to understand how this reframing may afford new insights. In doing so it also contributes to sociological thinking on eating practices and their reproduction as well as reflecting upon the ontological assertions of practice theory and its theory of social change. In particular this article argues that the re conceptualisation serves to clarify a sociological research agenda for eating practices associated with snacking. It is argued that setting snacking within routine temporalities and spatialities and as bound up in the recursivity between practices and relations is especially important for thinking about snacking sociologically. In common with applications of practice theory in the field of sustainability transitions the aim is to move beyond individualistic assumptions of behaviour change and instead situate snacking as an eating practice with health implications that has emerged within the social, temporal, economic and cultural organisation of everyday life. PMID- 26283572 TI - Which material ownership and responsibility in a circular economy? PMID- 26283571 TI - CAT-1 as a novel CAM stabilizes endothelial integrity and mediates the protective actions of L-Arg via a NO-independent mechanism. AB - Interendothelial junctions play an important role in the maintenance of endothelial integrity and the regulation of vascular functions. We report here that cationic amino acid transporter-1 (CAT-1) is a novel interendothelial cell adhesion molecule (CAM). We identified that CAT-1 protein localized at cell-cell adhesive junctions, similar to the classic CAM of VE-cadherin, and knockdown of CAT-1 with siRNA led to an increase in endothelial permeability. In addition, CAT 1 formed a cis-homo-dimer and showed Ca(2+)-dependent trans-homo-interaction to cause homophilic cell-cell adhesion. Co-immunoprecipitation assays showed that CAT-1 can associate with beta-catenin. Furthermore, we found that the sub cellular localization and function of CAT-1 are associated with cell confluency, in sub-confluent ECs CAT-1 proteins distribute on the entire surface and function as L-Arg transporters, but most of the CAT-1 in the confluent ECs are localized at interendothelial junctions and serve as CAMs. Further functional characterization has disclosed that extracellular L-Arg exposure stabilizes endothelial integrity via abating the cell junction disassembly of CAT-1 and blocking the cellular membrane CAT-1 internalization, which provides the new mechanisms for L-Arg paradox and trans-stimulation of cationic amino acid transport system (CAAT). These results suggest that CAT-1 is a novel CAM that directly regulates endothelial integrity and mediates the protective actions of L Arg to endothelium via a NO-independent mechanism. PMID- 26283573 TI - Relationship of serum 25-Hydroxyvitamin D (25[OH]D) levels and components of metabolic syndrome in prepubertal children. AB - OBJECTIVE: The relationship between 25-hydroxyvitamin D (25[OH]D) levels and the lipid and metabolic levels of the prepubertal normal population is unclear. Our goals were to investigate the association of serum 25(OH)D concentrations with lipid and metabolic levels in Korean prepubertal children ages 7-9 y. METHODS: We followed 205 children, ages 7-9 y in the Ewha Birth and Growth Cohort study, a prospective cohort sample established in 2001-2006, from July to August 2011. We studied the association of serum 25-hydroxyvitamin D (25[OH]D) levels with components of metabolic syndrome and insulin resistance indices using multivariate regression analysis adjusted for body mass index (BMI) z-scores. RESULTS: The mean age of the 205 subjects was 7.89 +/- 0.85 y, and the sample included 109 boys (53.2%). The average 25(OH)D levels of all participants was 25.0 +/- 5.4 ng/mL. After adjustment for age and sex, triacylglycerol levels were significantly associated with 25(OH)D (beta = -0.02, P = 0.02) concentrations even after adjustment for BMI z-scores (beta = -0.02, P = 0.04). However, other metabolic components were not correlated with 25(OH)D status. Those with the lowest quartile of 25(OH)D levels had the highest serum triacylglycerol levels (P = 0.04, Ptrend = 0.01). CONCLUSIONS: We found that serum 25(OH)D levels were negatively associated with serum triacylglycerol levels, even independently of adiposity, in prepubertal children. This study suggests that 25(OH)D insufficiency is related to metabolic syndrome via the derangement of triacylglycerol metabolism. PMID- 26283574 TI - TMAO: A small molecule of great expectations. AB - Trimethylamine N-oxide (TMAO) is a small organic compound whose concentration in blood increases after ingesting dietary l-carnitine and phosphatidylcholine. Recent clinical studies show a positive correlation between elevated plasma levels of TMAO and an increased risk for major adverse cardiovascular events defined as death, myocardial infarction, or stroke. Several experimental studies suggest a possible contribution of TMAO to the etiology of cardiovascular diseases by affecting lipid and hormonal homeostasis. On the other hand, TMAO rich seafood, which is an important source of protein and vitamins in the Mediterranean diet, has been considered beneficial for the circulatory system. Although in humans TMAO is known mainly as a waste product of choline metabolism, a number of studies suggest an involvement of TMAO in important biological functions in numerous organisms, ranging from bacteria to mammals. For example, cells use TMAO to maintain cell volume under conditions of osmotic and hydrostatic pressure stresses. In this article, we reviewed well-established chemical and biological properties of TMAO and dietary sources of TMAO, as well as looked at the studies suggesting possible involvement of TMAO in the etiology of cardiovascular and other diseases, such as kidney failure, diabetes, and cancer. PMID- 26283575 TI - Genetic evaluation of patients with Alstrom syndrome in the Polish population. AB - Alstrom syndrome (AS) is a rare syndromic form of obesity and type 2 diabetes (T2D) in children coexisting with retinal dystrophy and disorders of many organs caused by the mutations in ALMS1 gene. Aim of this study was to identify the causative mutations in ALMS1 in a group of 12 patients of Polish origin with clinical symptoms of AS, and their 21 first-degree relatives. Using DNA sequencing, nine different mutations including three novel were identified. These mutations were not present in 212 Polish individuals with no symptoms of AS, subjected to whole-exome sequencing and collected in a national registry. Looking for genotype-phenotype relationships, we confirmed a severe phenotype in a boy with homozygous mutation in exon 16, and a relationship between a presence of T2D and mutations in exon 19. Evaluation of the type of mutation and its clinical effects gives hope for earlier diagnosis of AS in future patients and more advanced therapeutic approaches for patients with already diagnosed AS. PMID- 26283576 TI - Detectability and anatomical correlation of middle ear cholesteatoma using fused thin slice non-echo planar imaging diffusion-weighted image and magnetic resonance cisternography (FTS-nEPID). AB - Cholesteatomas show high intensity in diffusion-weighted imaging (DWI). We performed fused thin slice non-echo planar imaging (EPI) DWI and magnetic resonance cisternography (FTS-nEPID) for cholesteatoma patients to increase the detectability of FTS-nEPID for cholesteatoma. The subjects are 77 consecutive patients who underwent FTS-nEPID as a preoperative study (mean age: 53.3+/-21.8, 47 men and 30 women). Otorhinolaryngologists performed the operations. We anatomically classified the middle ear into four portions. A radiologist evaluated the images for cholesteatoma and assessed the anatomical invasive range in four portions using only FTS-nEPID. We classified large cholesteatomas that invaded more than three portions and small ones that invaded less than two portions based on the results obtained from surgery, and calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). For all cholesteatomas with an existing diagnosis, the sensitivity, specificity, PPV, and NPV were 71%, 70%, 94%, and 27%, respectively. In anatomical evaluation, the sensitivity, specificity, PPV, and NPV were 49%, 85%, 77%, and 64%, respectively. For large cholesteatomas with an existing diagnosis, the sensitivity was 86%. In anatomical evaluation, the sensitivity, specificity, PPV, and NPV were 51%, 57%, 88%, and 18%, respectively. For small cholesteatomas with an existing diagnosis, the sensitivity, specificity, PPV, and NPV were 59%, 78%, 92%, and 30%, respectively. In anatomical evaluation, the sensitivity, specificity, PPV, and NPV were 40%, 85%, 60%, and 71%, respectively. FTS-nEPID may be useful for diagnosing cholesteatomas. Further research is needed for anatomical evaluation because there were many false-negative results. PMID- 26283578 TI - Cracking the humanitarian logistic coordination challenge: lessons from the urban search and rescue community. AB - The challenges of achieving successful inter-agency logistic coordination in preparing for and responding to natural disasters and complex emergencies are both well understood and well documented. However, although many of these challenges remain unresolved, the literature reveals that the organisations that form the urban search and rescue (USAR) community have attained a high level of coherence and interoperability that results in a highly efficient and effective response. Therefore, this paper uses the idea of 'borrowing' from other fields as it explores how the processes and procedures used by the USAR community might be applied to improve humanitarian logistic operations. The paper analyses the USAR model and explores how the resultant challenges might be addressed in a humanitarian logistic context. The paper recommends that further research be undertaken in order to develop a modified USAR model that could be operationalised by the international community of humanitarian logisticians. PMID- 26283577 TI - A non-invasive assessment of cardiopulmonary hemodynamics with MRI in pulmonary hypertension. AB - PURPOSE: We propose a method for non-invasive quantification of hemodynamic changes in the pulmonary arteries resulting from pulmonary hypertension (PH). METHODS: Using a two-element Windkessel model, and input parameters derived from standard MRI evaluation of flow, cardiac function and valvular motion, we derive: pulmonary artery compliance (C), mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), pulmonary capillary wedge pressure (PCWP), time averaged intra-pulmonary pressure waveforms and pulmonary artery pressures (systolic (sPAP) and diastolic (dPAP)). MRI results were compared directly to reference standard values from right heart catheterization (RHC) obtained in a series of patients with suspected pulmonary hypertension (PH). RESULTS: In 7 patients with suspected PH undergoing RHC, MRI and echocardiography, there was no statistically significant difference (p<0.05) between parameters measured by MRI and RHC. Using standard clinical cutoffs to define PH (mPAP>25mmHg), MRI was able to correctly identify all patients as having pulmonary hypertension, and to correctly distinguish between pulmonary arterial (mPAP>25mmHg, PCWP<15mmHg) and venous hypertension (mPAP>25mmHg, PCWP>15mmHg) in 5 of 7 cases. CONCLUSIONS: We have developed a mathematical model capable of quantifying physiological parameters that reflect the severity of PH. PMID- 26283579 TI - Rapid 3D Extrusion of Synthetic Tumor Microenvironments. AB - The spatial positioning of 3D tumor-mimetic microenvironments, containing multiple cell types, is controlled with a simple concentric flow device in a single step. A range of geometric architectures are demonstrated, and the migration of segregated tumor cells and macrophages is explored using drugs that inhibit heterotypic interactions. PMID- 26283580 TI - Identification of circadian gene variants in bipolar disorder in Latino populations. AB - BACKGROUND: Variations in circadian genes can impact biological rhythms. Given the rhythm disturbances that characterize bipolar disorder (BD), genes encoding components of molecular clocks are good candidate genes for the illness. METHODS: A family based association analysis of circadian gene single nucleotide polymorphisms (SNPs) and BD was conducted in Latino pedigrees. 884 individuals from 207 pedigrees (473BP phenotype and 411 unaffected family members) were genotyped. Family based single marker association testing was performed. Ancestral haplotypes (SNPs found to be in strong LD defined using confidence intervals) were also tested for association with BD. RESULTS: Multiple suggestive associations between circadian gene SNPs and BD were noted. These included CSNK1E (rs1534891, p=0.00689), ARNTL (rs3789327, p=0.021172), CSNK1D (rs4510078, p=0.022801), CLOCK (rs17777927, p=0.031664). Individually, none of the SNPs were significantly associated with BD after correction for multiple testing. However, a 4-locus CSNK1E haplotype encompassing the rs1534891 SNP (Z-score=2.685, permuted p=0.0076) and a 3-locus haplotype in ARNTL (Z-score=3.269, permuted p=0.0011) showed a significant association with BD. LIMITATIONS: Larger samples are required to confirm these findings and assess the relationship between circadian gene SNPs and BD in Latinos. CONCLUSIONS: The results suggest that ARNTL and CSKN1E variants may be associated with BD. Further studies are warranted to assess the relationships between these genes and BD in Latino populations. PMID- 26283582 TI - Dr. Sidney Licht: An Early Pioneer in the Development of Physical Medicine and Rehabilitation. PMID- 26283581 TI - Airway inflammation, cough and athlete quality of life in elite female cross country skiers: A longitudinal study. AB - The aim of this study was to investigate the effect of a season of cross-country training and racing on airway inflammation, cough symptoms, and athlete quality of life in female skiers. Eighteen elite female skiers performed sputum induction and completed the Leicester Cough Questionnaire (LCQ) and the Recovery-Stress Questionnaire (REST-Q) at three time points (T1 - May/Jun, T2 - Oct/Nov, T3 - Jan Mar) during the year. No changes were observed between T1 and T2. However, an increase in sputum eosinophils and lymphocytes (P < 0.05) and a significant change in all three domains of the LCQ were observed between T1 and T3 (P < 0.05). A significant association was found between the total yearly hours of training and the change in the total cell count (r(2) = 0.74; P = 0.006), and a number of other sputum cell counts between T1 and T3. No changes were observed for any domain of the REST-Q. The results of this study demonstrate that airway inflammation and cough symptoms are significantly increased in elite female cross country skiers across a year of training and racing. The increase in airway inflammation is related to the total amount of training and is worse during the winter months when athletes are training and racing in cold, dry air. PMID- 26283583 TI - Does disseminated granuloma annulare require treatment? Thoughts on the definition of "disease" in dermatology. PMID- 26283584 TI - Future distinguishing competencies of baccalaureate-educated registered nurses in nursing homes. AB - In view of the likelihood that the complexity of care required by those admitted to nursing homes will continue to increase, an expert consensus study was conducted to reach consensus on the competencies which distinguish baccalaureate educated registered nurses from other nursing staff working in nursing homes. Thirty-one international experts, identified through literature and our professional network, participated in a two-round web-based survey and an expert meeting. Experts reached consensus on 16 desirable competencies, including some not traditionally associated with nursing expertise e.g. being a team leader, role model and coach within the nursing team. These findings suggest that revision of current nursing curricula, nurse training programs and nursing home job profiles might be needed to meet the medically and psychologically complex needs of nursing home residents. PMID- 26283585 TI - Urgent suspected cancer referrals for childhood lymphadenopathy. PMID- 26283586 TI - Recoverable hybrid enzymatic biofuel cell with molecular oxygen-independence. AB - Enzymatic biofuel cells (EBFCs) have drawn great attentions because of its potential in energy conversion. However, designing of highly efficient EBFCs which can adapt to the anaerobic system is still a great challenge. In this study, we propose a novel hybrid enzymatic biofuel cell (HEBFC) which was fabricated by a glucose dehydrogenase modified bioanode and a solid-state silver oxide/silver (Ag2O/Ag) cathode. The as-assembled HEBFC exhibited an open circuit potential of 0.59V and a maximum power output of 0.281mWcm(-2) at 0.34V in air saturated buffer. Especially, due to the introduction of Ag2O/Ag, our HEBFC could also operate under anaerobic condition, while the maximum power output would reach to 0.275mWcm(-2) at 0.34V. Furthermore, our HEBFC had stable cycle operation and could keep high power output for a certain time as the result of the regeneration of Ag2O. Our work provides a new concept to develop EBFCs for efficient energy conversion in the future. PMID- 26283587 TI - Selective and sensitive determination of cypermethrin in fish via enzyme-linked immunosorbent assay-like method based on molecularly imprinted artificial antibody-quantum dot optosensing materials. AB - Molecularly imprinted silica layers appended to quantum dots (MIP-QDs) with customized selective artificial recognition sites were fabricated in this study by optimizing the ratio of the functional monomer to the template. Scanning electron microscopy, transmission electron microscopy, Brunauer-emmett-teller, Fourier transform infrared spectroscopy, and selectivity assay analyses were also performed. Results demonstrated that the selective fluorescence quenching properties of MIP-QDs toward cypermethrin (CYP) are due to strong interactions between these molecules. An enzyme-linked immunosorbent assay (ELISA)-like method based on the MIP-QDs was established under optimal conditions. The fluorescence quenching observed from this method showed a linear relationship with CYP concentration over the range of 0.05-60.0 mg/kg with a correlation coefficient of 0.9838. Good recovery (82.7-92.4%) and a relative standard deviation of less than 10.1% were obtained from fish samples spiked with three levels of CYP. This method also demonstrated a low detection limit of 1.2 MUg/kg. The ELISA-like method based on MIP-QDs can be successfully employed to detect residual of CYP in fish samples. PMID- 26283588 TI - High-throughput sample-to-answer detection of DNA/RNA in crude samples within functionalized micro-pipette tips. AB - We develop a micro-pipette tip-based nucleic acid test (MTNT) for high-throughput sample-to-answer detection of both DNA and RNA from crude samples including cells, bacteria, and solid plants, without the need of sample pretreatment and complex operation. MTNT consists of micro-pipette tips and embedded solid phase nucleic acid extraction membranes, and fully integrates the functions of nucleic acid extraction from crude samples, loop-mediated isothermal amplification (LAMP) of nucleic acids, and visual readout of assays. The total assaying time for DNA or RNA from a variety of crude samples ranges from 90 to 160 min. The limit of detection (LOD) of MTNT is 2 copies of plasmids containing the target nucleic acid fragments of Ebola virus, and 8 CFU of Escherichia coli carrying Ebola virus derived plasmids. MTNT can also detect CK-19 mRNA from as few as 2 cancer cells without complicated procedures such as RNA extraction and purification. We further demonstrate MTNT in a high-throughput format using an eight-channel pipette and a homemade mini-heater, with a maximum throughput of 40 samples. Compared with other point-of-care (POC) nucleic acid tests (NAT), MTNT could assay both DNA and RNA directly from liquid (cells/bacteria/blood) or solid (plant) samples in a straightforward, sensitive, high-throughput, and containment free manner, suggesting a considerable promise for low-cost and POC NAT in remote areas. PMID- 26283589 TI - The relationship between parent feeding styles and general parenting with loss of control eating in treatment-seeking overweight and obese children. AB - OBJECTIVE: To examine differences in parent feeding behaviors and general parenting of overweight children with and without loss of control (LOC) eating. METHOD: One-hundred-and-eighteen overweight and obese children (10.40 +/- 1.35 years; 53% female; 52% Caucasian; BMI-z: 2.06 +/- 0.39) and their parents (42.42 +/- 6.20 years; 91% female; 70% Caucasian; BMI: 31.74 +/- 6.96 kg/m(2) ) were seen at a baseline assessment visit for a behavioral intervention that targeted overeating. The Eating Disorder Examination, adapted for children (ChEDE) was administered to assess for LOC eating. Parents completed the Parental Feeding Styles Questionnaire (PFSQ) and the Child Feeding Questionnaire (CFQ) to assess parent feeding styles and behaviors. Children also completed a self-report measure of general parenting (Child Report of Parent Behavior Inventory, CRPBI 30). RESULTS: Forty-three children (36.40%) reported at least one LOC eating episode in the month prior to assessment. Parents who reported greater restriction and higher levels of pressure to eat were more likely to have children that reported LOC eating (ps < 0.05). Parents who utilized more instrumental feeding and prompting/encouragement to eat techniques were less likely to have children that reported LOC eating (ps < 0.05). Child-reported parenting behaviors were unrelated to child LOC eating (ps > 0.05). DISCUSSION: Parent feeding styles and behaviors appear to be differentially and uniquely related to LOC eating in treatment-seeking overweight and obese children. Future research is needed to determine if implementing interventions that target parent feeding behaviors may reduce LOC eating, prevent full-syndrome eating disorders, and reduce weight gain in youth. PMID- 26283591 TI - Resveratrol potentiates the effect of dexamethasone in rat model of acute lung inflammation. AB - Cigarette smoking is considered to be the main etiological factor in Chronic Obstructive Pulmonary Disease (COPD). In this study, we explored the potential of resveratrol, to reinstate the effectiveness of dexamethasone when administered as an adjunct in acute lung inflammation induced by cigarette smoke (CS) and lipopolysaccharide (LPS). CS and LPS instillation produced acute inflammatory response exhibited by increased leukocyte count, particularly neutrophils, total protein, MMP-9 activity, cytokines like TNF-alpha, IL-8 in bronchoalveolar lavage fluid (BALF) as well as elevated myeloperoxidase activity, and lipid peroxidation in lung. These alterations were not abated by dexamethasone (2.5mg/kg & 10mg/kg) and resveratrol (50mg/kg) alone. Combination of resveratrol (50mg/kg) and dexamethasone (2.5mg/kg) significantly reduced all inflammatory parameters. The protective effect of the combination was abolished when co-administered with sirtinol, a SIRT1 inhibitor. The results indicate that the combination therapy may serve as a potential approach for treating lung inflammatory conditions like COPD. PMID- 26283590 TI - Blockade of TNF-alpha-induced NF-kappaB signaling pathway and anti-cancer therapeutic response of dihydrotanshinone I. AB - The nuclear factor-kappaB (NF-kappaB) transcription factors control many physiological processes including inflammation, immunity, apoptosis, and angiogenesis. We identified dihydrotanshinone I as an inhibitor of NF-kappaB activation through our research on Salvia miltiorrhiza Bunge. In this study, we found that dihydrotanshinone I significantly inhibited the expression of NF kappaB reporter gene induced by TNF-alpha in a dose-dependent manner. And dihydrotanshinone I also inhibited TNF-alpha induced phosphorylation and degradation of IkappaBalpha, phosphorylation and nuclear translocation of p65. Furthermore, pretreatment of cells with this compound prevented the TNF-alpha induced expression of NF-kappaB target genes, such as anti-apoptosis (cIAP-1 and FLIP), proliferation (COX-2), invasion (MMP-9), angiogenesis (VEGF), and major inflammatory cytokines (TNF-alpha, IL-6, and MCP1). We also demonstrated that dihydrotanshinone I potentiated TNF-alpha-induced apoptosis. Moreover, dihydrotanshinone I significantly impaired activation of extracellular signal regulated kinase 1/2 (ERK1/2), p38 and stress-activated protein kinase/c-Jun NH2 terminal kinase (JNK/SAPK). In vivo studies demonstrated that dihydrotanshinone I suppressed the growth of HeLa cells in a xenograft tumor model, which could be correlated with its modulation of TNF-alpha production. Taken together, dihydrotanshinone I could be a valuable candidate for the intervention of NF kappaB-dependent pathological conditions such as inflammation and cancer. PMID- 26283592 TI - IL-1 provokes electrical abnormalities in rat atrial myocardium. AB - Using a micro-electrode technique we studied the effects of interleukin 1alpha and interleukin 1beta on bio-electric activity of rat atrial myocardium under normal conditions and after gradual stretching. Perfusion with interleukin 1alpha increased the duration of the action potential at the level of 90% re polarization. Stretch induced tachy-arrhythmia in the presence of interleukin 1alpha is mainly regulated via stretch increased nitric oxide production, while the ionotropic effect of the interleukin-1alpha during stretching is not pronounced. The perfusion with interleukin 1beta did not change the values of the duration of the action potentials at the levels of 25, 50 and 90% repolarization. The interleukin lbeta caused an appearance of extra-systolic patterns which turned into normal rhythm, alternating with periods of normal activity. The total intracellular nitric oxide level induced by both interleukin 1beta and stretching is balanced by interleukin-1beta induced cation influx. PMID- 26283593 TI - Therapeutic anti-NLGP monoclonal antibody for carcinoembryonic antigen expressing tumors is nontoxic to Swiss and BALB/c mice. AB - A murine monoclonal antibody (mAb), 1C8 was developed against a novel glycoprotein NLGP and its unique property to recognize carcinoembryonic antigen (CEA) was reported. Utilizing this CEA recognizing property, 1C8 is successful to restrict the growth of CEA(+) murine and human cancers both in vitro and in vivo. Here, we have thoroughly evaluated the toxicity profile of this mAb 1C8 on different physiological systems of both tumor-free and tumor-bearing Swiss and BALB/c mice. Effective concentration (25 MUg/mice) of 1C8 caused no behavioral changes in animals and no death was recorded. Moreover, little increase in the body and organ weights in all mice groups was noted. MAb 1C8 showed no adverse effect on the hematological system, but little hematostimulation was noticed, as evidenced by increased hemoglobin content, leukocyte count and lymphocyte numbers. Liver enzymes like alkaline phosphatase, SGOT, SGPT and nephrological products like urea and creatinine assessment confirmed no abnormalities in both hepatic and renal functions. Number of T cells, B cells, NK cells, macrophages and dendritic cells was upregulated in vivo by mAb treatment with significant downregulation of regulatory T cells. During this treatment serum levels of type 1 cytokines were upregulated over type 2 cytokines. This mAb 1C8 also did not induce any significant increase in antibody titer following treatment. Accumulated evidences from Swiss and BALB/c mice strongly suggest that this mAb 1C8 is completely safe, thus, can be recommended for further clinical trial for the therapy of CEA(+) tumors. PMID- 26283595 TI - Deletion of Prdm8 impairs development of upper-layer neocortical neurons. AB - Upper-layer (UL) neocortical neurons are the most prominent distinguishing features of the mammalian neocortex compared with those of the avian dorsal cortex and are vastly expanded in primates. However, little is known about the identities of the genes that control the specification of UL neurons. Here, we found that Prdm8, a member of the PR (PRDI-BF1 and RIZ homology) domain protein family, was specifically expressed in the postnatal UL neocortex, particular those in late-born RORbeta-positive layer IV neurons. We generated homozygous Prdm8 knockout (Prdm8 KO) mice and found that the deletion of Prdm8 causes growth retardation and a reduced brain weight, although the brain weight-to-body weight ratio is unchanged at postnatal day 8 (P8). Immunohistochemistry showed that the relative UL thickness, but not the thickness of the deep layer (DL), was significantly reduced in Prdm8 KO mice compared with wild-type (WT) mice. In addition, we found that a number of late-born Brn2-positive UL neurons were significantly decreased in Prdm8 KO mice. To identify genes regulated by Prdm8 during neocortical development, we compared expression profiling analysis in Prdm8 KO and WT mice, and identified some candidate genes. These results suggest that the proper expression of Prdm8 is required for the normal development and construction of UL neurons in the mammalian neocortex. PMID- 26283594 TI - Pictorial review of coronary anomalies in Tetralogy of Fallot. AB - Tetralogy of Fallot (TOF) classically consists of four characteristic features right ventricular outflow obstruction, right ventricular hypertrophy, ventricular septal defect and an overriding aorta. In addition there are multiple other associated cardiac anomalies, including coronary artery anomalies. In this review, the role of CT angiography and the spectrum of coronary anomalies will be discussed along with importance of such anomalies in the context of surgery. PMID- 26283596 TI - Multimodal Nanoparticle for Primary Tumor Delineation and Lymphatic Metastasis Mapping in a Head-and-Neck Cancer Rabbit Model. AB - 64 Cu-porphysome nanoparticles enable superior delineation of neoplastic tissues, metastatic lymph nodes, and vascular drainage on head and neck cancer orthotopic rabbit model using positron emission tomography imaging. Additionally, the nanoparticles exhibit selective fluorescence activation in tumor and metastatic lymph nodes, which permits intraoperative real-time visualization of disease tissues to precisely define surgical margins and prevents collateral damage during surgeries. PMID- 26283597 TI - Application of mechanochemistry to metal recovery from second-hand resources: a technical overview. AB - In the context of huge imbalance between increasing demand for metals and the finiteness of metal resources in nature, recycling metal from second-hand resources, especially e-waste, is of great importance, to embrace the sustainability challenge. Inspired by its hundreds of uses in extractive metallurgy, mechanochemistry has been introduced to recover metals from waste since the 1990s. The mechanochemical recycling process is technically feasible to recover metals from waste in a high yield, such as Pb recovery from cathode ray tube (CRT) funnel glass, Li and Co recovery from lithium-ion batteries, rare earth recovery from fluorescent lamps. In recovery from LCD screens, Cu recovery from waste printed circuit boards and Au, Mo and Ni recovery from waste. Particle size reduction, specific surface area increase, crystalline structure decomposition and bond breakage have been identified as the main changes induced by the mechanochemical processes in the studies. Also, the activation energy required decreases and reaction activity increases, subsequently. This paper presents a technical overview of the applications of mechanochemistry to metal recycling from waste. The current application pattern, reaction mechanisms, equipment used, method procedures, and the future research direction are discussed in detail. This work presents the limitation of current mechanochemical application in metal recovery and gives a perspective of the future development of mechanochemistry as well. PMID- 26283598 TI - Strategies for developing Ki67 as a useful biomarker in breast cancer. AB - Increased proliferation is a hallmark of malignant tumors. The proliferation marker Ki67 has been investigated as a breast cancer biomarker, but despite 32 years of research the best cutpoints and the best methods for determination are still under debate. This review is based on an overview on the efforts to standardize Ki67 and to optimize its performance that was presented at the St. Gallen oncology conference 2015. The clinical validity of Ki67 as a prognostic marker as well as a predictive marker (in the neoadjuvant setting) has been shown in several meta-analyses. Depending on cohort characteristics, molecular subtype and clinical setting, Ki67 is a prognostic marker, a predictive marker, or both. Many different cutpoints for Ki67 have been reported, but it is has not been possible to determine an evidence-based "optimal" cutpoint. This supports the view that Ki67 is continuous marker, reflecting the continuous variation of the proliferation rate in different tumors. We should probably stop looking for an "optimal" cutpoint for Ki67 because it simply does not exist. It is evident from the results of several ring trials that intermediate levels of Ki67 are particularly difficult for standardization. Due to the low analytical validity in the intermediate range as well as intratumoral heterogeneity, the clinical utility of intermediate Ki67 levels is limited. Clinical decisions should not be based on small differences in the intermediate range and additional molecular tests might be necessary for tumors with intermediate Ki67 levels. For the two groups of tumors with a very low or a very high Ki67 a clinical interpretation could be straightforward. Despite these limitations, the assessment of proliferation is a central parameter for tumor characterization and an important element of the pathological assessment. PMID- 26283600 TI - Obesity, insulin resistance and breast cancer outcomes. AB - There is growing evidence that obesity is associated with poor outcomes in early stage breast cancer. This paper addresses four current areas of focus: 1. Is obesity associated with poor outcomes in all biologic subtypes of breast cancer? 2. Does obesity effect AI efficacy or estrogen suppression in the adjuvant setting? 3. What are the potential biologic underpinnings of the obesity-breast cancer association? 4. Are intervention studies warranted? If so, which interventions in which populations? Research is needed to resolve these questions; intervention trials involving lifestyle interventions or targeting the biology postulated to link obesity and cancer are recommended. PMID- 26283599 TI - Prognostic significance of nodal involvement region in clinical stage IIIc breast cancer patients who received primary systemic treatment, surgery, and radiotherapy. AB - OBJECTIVES: To evaluate the prognostic influence of involvement of both internal mammary nodes (IMNs) and supraclavicular nodes (SCNs) in clinical stage IIIc breast cancer patients who underwent primary systemic treatment, surgery, and radiotherapy (RT). MATERIALS AND METHODS: Between 2001 and 2009, 110 breast cancer patients with IMN or SCN involvement were treated with primary systemic treatment followed by surgery and RT. The median age was 50 years. Clinical N stage was cN3b and cN3c in 29 (26.4%) and 81 (73.6%) patients, respectively. Among the 81 patients with cN3c disease, 18 patients had both IMN and SCN involvement. Primary systemic treatment regimen was most commonly doxorubicin plus docetaxel (54.5%) or cyclophosphamide (20.0%). Mastectomy was performed in 71 (64.5%) patients. The RT dose delivered to the chest wall or whole breast was 50-50.4 Gy in 25-28 fractions. IMN and SCN regions were irradiated in 77 (70.0%) and 107 (97.6%) patients, respectively. RESULTS: At a median follow-up of 57.4 months (range, 8.6-149.9 months), 44 patients (40.0%) developed disease recurrence. Among the 18 patients with both IMN and SCN involvement, 12 patients experienced disease recurrence and 11 of them had distant metastases. The 5-year disease-free survival (DFS) and overall survival (OS) of all patients were 60.2% and 75.5%, respectively. Decreased DFS and OS were observed in the 18 patients with both IMN and SCN involvement (5-year rates, 33.3% and 50.0%; P = 0.0051 and 0.0010, respectively). CONCLUSION: Involvement of both IMNs and SCNs was associated with worse survival outcomes in patients with clinical stage IIIc breast cancer. PMID- 26283601 TI - Efficient test for nonlinear dependence of two continuous variables. AB - BACKGROUND: Testing dependence/correlation of two variables is one of the fundamental tasks in statistics. In this work, we proposed a new way of testing nonlinear dependence between two continuous variables (X and Y). RESULTS: We addressed this research question by using CANOVA (continuous analysis of variance, software available at https://sourceforge.net/projects/canova/). In the CANOVA framework, we first defined a neighborhood for each data point related to its X value, and then calculated the variance of the Y value within the neighborhood. Finally, we performed permutations to evaluate the significance of the observed values within the neighborhood variance. To evaluate the strength of CANOVA compared to six other methods, we performed extensive simulations to explore the relationship between methods and compared the false positive rates and statistical power using both simulated and real datasets (kidney cancer RNA seq dataset). CONCLUSIONS: We concluded that CANOVA is an efficient method for testing nonlinear correlation with several advantages in real data applications. PMID- 26283603 TI - ECG Response: August 18, 2015. PMID- 26283602 TI - Accountable Care Organizations: Ensuring Focus on Cardiovascular Health. PMID- 26283604 TI - Infected Abdominal Aortic Aneurysm Attributable to Haemophilus influenzae: Rapid Changes of Imaging Findings. PMID- 26283605 TI - The Forgotten Valve: Isolated Severe Tricuspid Valve Stenosis. PMID- 26283606 TI - Letter by Chhabra and Spodick Regarding Article, "Clinical Profile and Influences on Outcomes in Patients Hospitalized for Acute Pericarditis". PMID- 26283607 TI - Letter by Lazaros et al Regarding Article, "Clinical Profile and Influences on Outcomes in Patients Hospitalized for Acute Pericarditis". PMID- 26283608 TI - Response to Letters Regarding Article, "Clinical Profile and Influences on Outcomes in Patients Hospitalized for Acute Pericarditis". PMID- 26283609 TI - RE: Is Bad Luck the Main Cause of Cancer? PMID- 26283610 TI - Response. PMID- 26283611 TI - RE: Androgen Receptor Expression and Outcomes in Early Breast Cancer: A Systematic Review and Meta-Analysis. PMID- 26283612 TI - Response. PMID- 26283613 TI - The Subjective Court Experiences of Intimate Partner Violence Victims: Does Motherhood Matter? AB - Many women with children experience intimate partner violence (IPV). These survivors are particularly important to assist, because countless have complex safety concerns related to their children. Mothers' concerns about their children have been shown to impact their decision making related to abuse, but researchers have not closely explored what happens during mothers' interactions with help sources. This study examined whether women with (n = 98) and without (n = 44) children differ in a) their court experiences through their perceptions of procedural and distributive justice, and b) the context of their lives surrounding the court experience. We also explored the relationship between contextual factors and procedural and distributive justice. Results indicate participants were relatively satisfied with their court experiences, despite experiencing reabuse, danger, and fear throughout court processes. Mothers reported significantly higher levels of distributive justice and contact with the abusive partner than non-mothers. However, mothers did not differ significantly from non-mothers with regard to procedural justice, fear, danger, reabuse or reliance on the abusive partner. Results of multiple regression analyses indicated the interaction between fear and motherhood significantly predicted participants' perceptions of distributive justice, as did the interaction between danger and motherhood. In these interactions, mothers' fear and perceptions of danger were not related to their perception of distributive justice. However, non mothers who reported higher levels of fear and danger perceived less distributive justice. Results suggest mothers and non-mothers enter the system with similar life contexts, and that these contextual factors impact their perceptions of court outcomes differently. PMID- 26283614 TI - A peculiar etiology of acute heart failure: adrenergic myocarditis. AB - Pheochromocytoma can occur with a variety of cardiovascular signs and symptoms, and this tumor can also precipitate an acute heart failure associated with the typical clinical and instrumental findings of myocarditis. This peculiar etiology of acute myocarditis, known as "adrenergic myocarditis," should be suspected when specific "red flags" of pheochromocytoma such as headache, palpitations, diaphoresis, hypertension, orthostatic hypotension, and left ventricular dysfunction suggesting Takotsubo syndrome are detected. In fact, its diagnosis allows a specific targeted therapy. PMID- 26283615 TI - Thirty-day mortality in ED patients with new onset atrial fibrillation and actively treated cancer. AB - OBJECTIVES: Studies suggest that inflammatory, autonomic, and coagulation alterations associated with cancer may increase incident atrial fibrillation (AF). New-onset AF is associated with increased mortality in other nonneoplastic disease processes. We investigated the association of active cancer with 30-day mortality in emergency department (ED) patients with new-onset AF. METHODS: We conducted an analysis within an observational cohort study at a tertiary care hospital that included ED patients with new-onset AF. The exposure variable was presence of active cancer. We defined active cancer as the patient received chemotherapy, radiotherapy, or recent cancer-related surgery within 90 days of the ED visit. The primary outcome was 30-day mortality. Logistic regression was used to analyze the association between cancer status and 30-day mortality adjusting for patient age and sex. RESULTS: During the 5.5-year study period, 420 patients with new-onset AF were included in our cohort, including 37 (8.8%) with active cancer. Patients with active cancer had no clinically relevant differences in their hemodynamic stability. Among the 37 patients with active cancer, 9 (24%) died within 30 days. Of the 383 patients without active cancer, 11 (3%) died within 30 days. After adjusting for age and sex, active cancer was an independent predictor of 30-day mortality, with an adjusted odds ratio of 10.8 (95% confidence interval, 3.8-31.1). CONCLUSIONS: Among ED patients with new-onset AF, active cancer appears to be associated with 11-fold increased odds of 30-day mortality; new-onset AF may represent progressive organ dysfunction leading to an increased risk of short-term mortality in patients with cancer. PMID- 26283617 TI - Treatment patterns in inpatient depression care. AB - This study aimed to identify latent patterns of treatment combinations in inpatient depression care. A secondary analysis of routinely collected data on inpatient depression treatment from 2133 patients was conducted. Exploratory latent class modeling was used to identify distinct classes of treatment combinations based on antidepressant medication, psychotherapeutic interventions, and additional treatments. The classes were compared with regard to patient characteristics and treatment outcomes. Eight different classes of inpatient treatment combinations could be identified: 22.8% of the patients were treated with a combination labelled "standard modern antidepressants", 14.6% with "standard tricyclic antidepressants", 12.2% with "high intensity innovative strategies", 12.1% with "standard selective-reuptake-inhibitors", and 11.6% with "low intensity", 9.6% with "somatic", 8.8% with "high intensity traditional", and 8.3% with "high intensity psychosocial" care, respectively. Patients treated with different patterns of interventions differed statistically significantly regarding demographic and clinical characteristics. Responder rates ranged from 68.4% to 86.6% across treatment classes. The presented attempt of empirical modeling of a complex multifactorial intervention by means of latent class analysis proved to be a promising way of capturing the complexity of routine inpatient depression treatment. The identified classes of treatment combinations may provide relevant information for a re-evaluation and improvement of inpatient depression treatment strategies. PMID- 26283616 TI - Derivation and preliminary validation of a risk score to predict 30-day ED revisits for sickle cell pain. AB - BACKGROUND: Emergency department (ED) revisits and 30-day readmissions have been proposed as markers for quality of ED care for sickle cell disease (SCD). OBJECTIVE: To create a scoring system that quantifies the risk of 30-day revisit after ED discharge for SCD vaso-occlusive pain METHODS: This was a dual-center retrospective derivation and validation cohort study. The derivation was performed at an academic, tertiary care center and the validation at an urban community hospital. The primary outcome was revisit to the ED within 30 days after an ED discharge for SCD pain. Recursive partitioning was used to derive a scoring system to predict 30-day revisits. RESULTS: Of a total of 1456 ED visits for SCD pain, there were 680 ED discharges (admission rate of 53%) in 193 unique individuals included in the derivation cohort. There were 240 (35.3%) 30-day revisits. Of a total of 126 ED visits for SCD, there were 79 ED discharges in 41 unique individuals in the validation cohort. The final risk score included 4 variables: (1) age, (2) insurance status, (3) triage pain score, and (4) amount of opioids administered during the ED visit. Possible scores range from 0 to 6. The areas under the receiver operating characteristic curves were 0.746 (95% confidence interval, 0.71-0.78-derivation cohort) and 0.753 (95% confidence interval, 0.65-0.86-validation cohort). A cutoff of 4 or greater identified 60% of 30-day ED revisits in the derivation cohort and 80% of revisits in the validation cohort. CONCLUSIONS: A risk score can identify ED visits for SCD pain with high risk of 30-day revisit. PMID- 26283619 TI - Applying the Triangle Method for the parameterization of irrigated areas as input for spatially distributed hydrological modeling - Assessing future drought risk in the Gaza Strip (Palestine). AB - In the Mediterranean region, particularly in the Gaza strip, an increased risk of drought is among the major concerns related to climate change. The impacts of climate change on water availability, drought risk and food security can be assessed by means of hydro-climatological modeling. However, the region is prone to severe observation data scarcity, which limits the potential for robust model parameterization, calibration and validation. In this study, the physically based, spatially distributed hydrological model WaSiM is parameterized and evaluated using satellite imagery to assess hydrological quantities. The Triangle Method estimates actual evapotranspiration (ETR) through the Normalized Difference Vegetation Index (NDVI) and land surface temperature (LST) provided by Landsat TM imagery. So-derived spatially distributed evapotranspiration is then used in two ways: first a subset of the imagery is used to parameterize the irrigation module of WaSiM and second, withheld scenes are applied to evaluate the performance of the hydrological model in the data scarce study area. The results show acceptable overall correlation with the validation scenes (r=0.53) and an improvement over the usual irrigation parameterization scheme using land use information exclusively. This model setup is then applied for future drought risk assessment in the Gaza Strip using a small ensemble of four regional climate projections for the period 2041-2070. Hydrological modeling reveals an increased risk of drought, assessed with an evapotranspiration index, compared to the reference period 1971-2000. Current irrigation procedures cannot maintain the agricultural productivity under future conditions without adaptation. PMID- 26283618 TI - Ecotoxicoparasitology: Understanding mercury concentrations in gut contents, intestinal helminths and host tissues of Alaskan gray wolves (Canis lupus). AB - Some gastrointestinal helminths acquire nutrients from the lumen contents in which they live; thus, they may be exposed to non-essential elements, such as mercury (Hg), during feeding. The objectives of this study were: 1) determine the total mercury concentrations ([THg]) in Gray wolves (Canis lupus) and their parasites, and 2) use stable isotopes to evaluate the trophic relationships within the host. [THg] and stable isotopes (C and N) were determined for helminths, host tissues, and lumen contents from 88 wolves. Sixty-three wolves contained grossly visible helminths (71.5%). The prevalence of taeniids and ascarids was 63.6% (56/88) and 20.5% (18/88), respectively. Nine of these 63 wolves contained both taeniids and ascarids (14.3%). All ascarids were determined to be Toxascaris leonina. Taenia species present included T. krabbei and T. hydatigena. Within the GI tract, [THg] in the lumen contents of the proximal small intestine were significantly lower than in the distal small intestine. There was a significant positive association between hepatic and taeniid [THg]. Bioaccumulation factors (BAF) ranged from <1 to 22.9 in taeniids, and 1.1 to 12.3 in T. leonina. Taeniid and ascarid BAF were significantly higher than 1, suggesting that both groups are capable of THg accumulation in their wolf host. delta13C in taeniids was significantly lower than in host liver and skeletal muscle. [THg] in helminths and host tissues, in conjunction with stable isotope (C and N) values, provides insight into food-web dynamics of the host GI tract, and aids in elucidating ecotoxicoparasitologic relationships. Variation of [THg] throughout the GI tract, and between parasitic groups, underscores the need to further evaluate the effect(s) of feeding niche, and the nutritional needs of parasites, as they relate to toxicant exposure and distribution within the host. PMID- 26283620 TI - A high-precision sampling scheme to assess persistence and transport characteristics of micropollutants in rivers. AB - Increasing numbers of organic micropollutants are emitted into rivers via municipal wastewaters. Due to their persistence many pollutants pass wastewater treatment plants without substantial removal. Transport and fate of pollutants in receiving waters and export to downstream ecosystems is not well understood. In particular, a better knowledge of processes governing their environmental behavior is needed. Although a lot of data are available concerning the ubiquitous presence of micropollutants in rivers, accurate data on transport and removal rates are lacking. In this paper, a mass balance approach is presented, which is based on the Lagrangian sampling scheme, but extended to account for precise transport velocities and mixing along river stretches. The calculated mass balances allow accurate quantification of pollutants' reactivity along river segments. This is demonstrated for representative members of important groups of micropollutants, e.g. pharmaceuticals, musk fragrances, flame retardants, and pesticides. A model-aided analysis of the measured data series gives insight into the temporal dynamics of removal processes. The occurrence of different removal mechanisms such as photooxidation, microbial degradation, and volatilization is discussed. The results demonstrate, that removal processes are highly variable in time and space and this has to be considered for future studies. The high precision sampling scheme presented could be a powerful tool for quantifying removal processes under different boundary conditions and in river segments with contrasting properties. PMID- 26283622 TI - Food insecurity and malnutrition in Chinese elementary school students. AB - It has been shown that food insecurity is associated with poor diet quality and unfavourable health outcomes. However, little is known about the potential effects of food insecurity on the overall malnutrition status among children. In this study, we investigated the prevalence of food insecurity among 1583 elementary school students, aged 6-14 years, living in Chinese rural areas and examined its association with four malnutrition signs, including rickets sequelae, anaemia, stunting and wasting. Information on food security was collected via questionnaires. Rickets sequelae were assessed by an experienced paediatrician during the interview. Anaemia was determined by the WHO Hb thresholds adjusted by the local altitude. Weight and height were measured during the interview. Stunting and wasting were then evaluated according to WHO child growth standards (2007). We examined the association between food insecurity and the number of malnutrition signs (total number = 4), and the likelihood of having severe malnutrition (presence of 3+ signs), after adjusting for potential confounders, such as age, social-economic status and dietary intakes. During the previous 12 months, the overall prevalence of food insecurity was 6.1% in the entire studied population and 16.3% in participants with severe malnutrition. Participants with food insecurity had a slightly higher number of malnutrition signs (1.14 v. 0.96; P=0.043) relative to those who were food secure, after adjusting for potential confounders. Food insecurity was also associated with increased likelihood of having severe malnutrition (adjusted OR 3.08; 95% CI 1.47, 6.46; P=0.003). In conclusion, food insecurity is significantly associated with malnutrition among Chinese children in this community. PMID- 26283624 TI - Reversal of acquired hepatocerebral degeneration with living donor liver transplantation. PMID- 26283623 TI - Barriers and enablers to implementing antenatal magnesium sulphate for fetal neuroprotection guidelines: a study using the theoretical domains framework. AB - BACKGROUND: Strong evidence supports administration of magnesium sulphate prior to birth at less than 30 weeks' gestation to prevent very preterm babies dying or developing cerebral palsy. This study was undertaken as part of The WISH (Working to Improve Survival and Health for babies born very preterm) Project, to assess health professionals' self-reported use of antenatal magnesium sulphate, and barriers and enablers to implementation of 2010 Australian and New Zealand clinical practice guidelines. METHODS: Semi-structured, one-to-one interviews were conducted with obstetric and neonatal consultants and trainees, and midwives in 2011 (n = 24) and 2012-2013 (n = 21) at the Women's and Children's Hospital, South Australia. Transcribed interview data were coded using the Theoretical Domains Framework (describing 14 domains related to behaviour change) for analysis of barriers and enablers. RESULTS: In 2012-13, health professionals more often reported 'routinely' or 'sometimes' administering or advising their colleagues to administer magnesium sulphate for fetal neuroprotection (86% in 2012-13 vs. 46% in 2011). 'Knowledge and skills', 'memory, attention and decision processes', 'environmental context and resources', 'beliefs about consequences' and 'social influences' were key domains identified in the barrier and enabler analysis. Perceived barriers were the complex administration processes, time pressures, and the unpredictability of preterm birth. Enablers included education for staff and women at risk of very preterm birth, reminders and 'prompts', simplified processes for administration, and influential colleagues. CONCLUSIONS: This study has provided valuable data on barriers and enablers to implementing magnesium sulphate for fetal neuroprotection, with implications for designing and modifying future behaviour change strategies, to ensure optimal uptake of this neuroprotective therapy for very preterm infants. PMID- 26283625 TI - Contrasting responses of male and female foraging effort to year-round wind conditions. AB - There is growing interest in the effects of wind on wild animals, given evidence that wind speeds are increasing and becoming more variable in some regions, particularly at temperate latitudes. Wind may alter movement patterns or foraging ability, with consequences for energy budgets and, ultimately, demographic rates. These effects are expected to vary among individuals due to intrinsic factors such as sex, age or feeding proficiency. Furthermore, this variation is predicted to become more marked as wind conditions deteriorate, which may have profound consequences for population dynamics as the climate changes. However, the interaction between wind and intrinsic effects has not been comprehensively tested. In many species, in particular those showing sexual size dimorphism, males and females vary in foraging performance. Here, we undertook year-round deployments of data loggers to test for interactions between sex and wind speed and direction on foraging effort in adult European shags Phalacrocorax aristotelis, a pursuit-diving seabird in which males are c. 18% heavier. We found that foraging time was lower at high wind speeds but higher during easterly (onshore) winds. Furthermore, there was an interaction between sex and wind conditions on foraging effort, such that females foraged for longer than males when winds were of greater strength (9% difference at high wind speeds vs. 1% at low wind speeds) and when winds were easterly compared with westerly (7% and 4% difference, respectively). The results supported our prediction that sex-specific differences in foraging effort would become more marked as wind conditions worsen. Since foraging time is linked to demographic rates in this species, our findings are likely to have important consequences for population dynamics by amplifying sex-specific differences in survival rates. PMID- 26283621 TI - Mechanism, factors, and physiological role of nonsense-mediated mRNA decay. AB - Nonsense-mediated mRNA decay (NMD) is a translation-dependent, multistep process that degrades irregular or faulty messenger RNAs (mRNAs). NMD mainly targets mRNAs with a truncated open reading frame (ORF) due to premature termination codons (PTCs). In addition, NMD also regulates the expression of different types of endogenous mRNA substrates. A multitude of factors are involved in the tight regulation of the NMD mechanism. In this review, we focus on the molecular mechanism of mammalian NMD. Based on the published data, we discuss the involvement of translation termination in NMD initiation. Furthermore, we provide a detailed overview of the core NMD machinery, as well as several peripheral NMD factors, and discuss their function. Finally, we present an overview of diseases associated with NMD factor mutations and summarize the current state of treatment for genetic disorders caused by nonsense mutations. PMID- 26283627 TI - Margaret McCartney: The government's plan to blame and shame people for having disease. PMID- 26283626 TI - Prevalence of PALB2 mutations in Australian familial breast cancer cases and controls. AB - INTRODUCTION: PALB2 is emerging as a high-penetrance breast cancer predisposition gene in the order of BRCA1 and BRCA2. However, large studies that have evaluated the full gene rather than just the most common variants in both cases and controls are required before all truncating variants can be included in familial breast cancer variant testing. METHODS: In this study we analyse almost 2000 breast cancer cases sourced from individuals referred to familial cancer clinics, thus representing typical cases presenting in clinical practice. These cases were compared to a similar number of population-based cancer-free controls. RESULTS: We identified a significant excess of truncating variants in cases (1.3 %) versus controls (0.2 %), including six novel variants (p = 0.0001; odds ratio (OR) 6.58, 95 % confidence interval (CI) 2.3-18.9). Three of the four control individuals carrying truncating variants had at least one relative with breast cancer. There was no excess of missense variants in cases overall, but the common c.1676A > G variant (rs152451) was significantly enriched in cases and may represent a low penetrance polymorphism (p = 0.002; OR 1.24 (95 % CI 1.09-1.47). CONCLUSIONS: Our findings support truncating variants in PALB2 as high-penetrance breast cancer susceptibility alleles, and suggest that a common missense variant may also lead to a low level of increased breast cancer risk. PMID- 26283628 TI - Porcine epidemic diarrhea virus inhibits dsRNA-induced interferon-beta production in porcine intestinal epithelial cells by blockade of the RIG-I-mediated pathway. AB - BACKGROUND: The lack of optimal porcine cell lines has severely impeded the study and progress in elucidation of porcine epidemic diarrhea virus (PEDV) pathogenesis. Vero cell, an African green monkey kidney cell line, was often used to isolate and propagate PEDV. Nonetheless, the target cells of PEDV in vivo are intestinal epithelial cells, during infection, intestinal epithelia would be damaged and resulted in digestive disorders. The immune functions of porcine epithelial cells and interactions with other immune cell populations display a number of differences compared to other species. Type I interferon (IFN) plays an important role in antiviral immune response. Limited reports showed that PEDV could inhibit type I interferon production. In this study, porcine small intestinal epithelial cells (IECs), the target cells of PEDV, were used as the infection model in vitro to identify the possible molecular mechanisms of PEDV inhibition IFN-beta production. RESULTS: PEDV not only failed to induce IFN-beta expression, but also inhibited dsRNA-mediated IFN-beta production in IECs. As the key IFN-beta transcription factors, we found that dsRNA-induced activation of IFN regulatory factor 3 (IRF-3) was inhibited after PEDV infection, but not nuclear factor-kappaB (NF-kappaB). To identify the mechanism of PEDV intervention with dsRNA-mediated IFN-beta expression more accurately, the role of individual molecules of RIG-I signaling pathway were investigated. In the upstream of IRF-3, TANK-binding kinase 1 (TBK1)-or inhibitor of kappaB kinase-epsilon (IKKepsilon) mediated IFN-beta production was not blocked by PEDV, while RIG-I-and its adapter molecule IFN-beta promoter stimulator 1 (IPS-1)-mediated IFN-beta production were completely inhibited after PEDV infection. CONCLUSION: Taken together, our data demonstrated for the first time that PEDV infection of its target cell line, IECs, inhibited dsRNA-mediated IFN-beta production by blocking the activation of IPS-1 in RIG-I-mediated pathway. Our studies offered new visions in understanding of the interaction between PEDV and host innate immune system. PMID- 26283629 TI - Placebo-controlled randomized clinical trial of fish oil's impact on fatigue, quality of life, and disease activity in Systemic Lupus Erythematosus. AB - INTRODUCTION: A recent metabolomic screen of sera from patients with Systemic Lupus Erythematosus (SLE) found reduction of antioxidants and substrates for energy generation. These metabolic alterations may underlie one of the most common features of SLE--fatigue. The metabolomic studies also noted reduced omega 3 fatty acids, which are powerful anti- oxidants. This deficiency may be causally related to oxidative stress, inflammation, disease activity, and fatigue in SLE. Supplementation of omega-3 fatty acids using fish oil in SLE has been shown to reduce oxidative stress in other studies. The objective of this study is to evaluate the effect of fish oil supplementation on clinical measures of fatigue, quality of life, and disease activity as part of a randomized clinical trial. METHODS: Fifty SLE patients recruited in outpatient clinics were randomized 1:1 to fish oil supplementation or olive oil placebo, and blinded to their treatment group. At baseline and after 6 months of treatment, RAND Short Form-36 (RAND SF 36), Fatigue Severity Scale (FSS), SLE Disease Activity Index (SLEDAI), and Physician Global Assessment (PGA) were completed; serum was also collected for soluble mediator analysis. RESULTS: Thirty-two patients completed the study. PGA improved significantly in the fish oil group compared with the placebo group (p = 0.015). The RAND SF-36 Energy/fatigue and Emotional well-being scores demonstrated improvement trends (p = 0.092 and 0.070). No clear difference was seen in FSS and SLEDAI (p = 0.350 and p = 0.417). Erythrocyte sedimentation rate and serum IL-12 were reduced (p = 0.008 and p = 0.058); while serum IL-13 was increased by fish oil supplementation (p = 0.033). CONCLUSIONS: In this randomized, placebo-controlled 6-month trial, SLE patients randomized to fish oil supplementation demonstrated improvement in their PGA, RAND SF-36, and some circulating inflammatory markers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02021513 (registered 13 December 2013). PMID- 26283630 TI - In vitro antimicrobial activity of plants used in traditional medicine in Gurage and Silti Zones, south central Ethiopia. AB - BACKGROUND: To overcome the escalating problems associated with infectious diseases and drug resistance, discovery of new antimicrobials is crucial. The present study aimed to carry out in vitro antimicrobial analysis of 15 medicinal plant species selected according to their traditional medicinal uses in Gurage and Silti Zones, south central Ethiopia. METHODS: Ethanol extracts of various plant parts were investigated for their antimicrobial activity against 20 bacterial and one yeast strains. The minimum inhibitory concentration (MIC) was determined by broth microdilution method. RESULTS: Asparagus africanus, Guizotia schimperi, Lippia adoensis var. adoensis and Premna schimperi were active against Candida albicans, Enterococcus faecalis and Staphylococcus aureus at a concentration of 512 MUg/ml or lower. Strong antibacterial activity (MIC>=128 MUg/ml) was observed for G. schimperi extract against 17 resistant and sensitive Staphylococcus strains, at a concentration comparable to standard antibiotics. Moreover, this extract showed higher antibacterial activity for the test against S. aureus ATCC 33591, ATCC 33592, SA3 and SA5 strains (128-256 MUg/ml) than oxacillin (512 MUg/ml). CONCLUSIONS: The study revealed in vitro antibacterial activity of plants used in folk medicine in south central Ethiopia. The usefulness of these plants, in particular of G. schimperi, should be confirmed through further phytochemical and toxicity analyses. PMID- 26283631 TI - Identification of stable QTLs for vegetative and reproductive traits in the microvine (Vitis vinifera L.) using the 18 K Infinium chip. AB - BACKGROUND: The increasing temperature associated with climate change impacts grapevine phenology and development with critical effects on grape yield and composition. Plant breeding has the potential to deliver new cultivars with stable yield and quality under warmer climate conditions, but this requires the identification of stable genetic determinants. This study tested the potentialities of the microvine to boost genetics in grapevine. A mapping population of 129 microvines derived from Picovine x Ugni Blanc flb, was genotyped with the Illumina(r) 18 K SNP (Single Nucleotide Polymorphism) chip. Forty-three vegetative and reproductive traits were phenotyped outdoors over four cropping cycles, and a subset of 22 traits over two cropping cycles in growth rooms with two contrasted temperatures, in order to map stable QTLs (Quantitative Trait Loci). RESULTS: Ten stable QTLs for berry development and quality or leaf area were identified on the parental maps. A new major QTL explaining up to 44 % of total variance of berry weight was identified on chromosome 7 in Ugni Blanc flb, and co-localized with QTLs for seed number (up to 76 % total variance), major berry acids at green lag phase (up to 35 %), and other yield components (up to 25 %). In addition, a minor QTL for leaf area was found on chromosome 4 of the same parent. In contrast, only minor QTLs for berry acidity and leaf area could be found as moderately stable in Picovine. None of the transporters recently identified as mutated in low acidity apples or Cucurbits were included in the several hundreds of candidate genes underlying the above berry QTLs, which could be reduced to a few dozen candidate genes when a priori pertinent biological functions and organ specific expression were considered. CONCLUSIONS: This study combining the use of microvine and a high throughput genotyping technology was innovative for grapevine genetics. It allowed the identification of 10 stable QTLs, including the first berry acidity QTLs reported so far in a Vitis vinifera intra-specific cross. Robustness of a set of QTLs was assessed with respect to temperature variation. PMID- 26283632 TI - Nilotinib (TasignaTM) in the treatment of early diffuse systemic sclerosis: an open-label, pilot clinical trial. AB - INTRODUCTION: Tyrosine kinase inhibitors (TKI) are medications of interest in the treatment of Systemic Sclerosis (SSc) because of their ability to inhibit pathways involved in fibrosis. In this open-label pilot trial, our objectives were to assess the safety, efficacy, and molecular change associated with treatment of patients with diffuse cutaneous (dc)SSc with the TKI nilotinib (TasignaTM). METHODS: Ten adult patients with early dcSSc were treated with nilotinib. Primary endpoints were safety and change in modified Rodnan Skin Score (MRSS) after 6 months. Lesional skin biopsies at baseline, 6 and 12 months of treatment were assessed by histopathology, immunohistochemistry, and DNA microarray. RESULTS: Patients had early and active dcSSc with median disease duration of 0.7 years (range 0.5, 1.7) and increasing MRSS in the month prior to baseline (mean +2.9, p=0.02). Seven out of ten patients completed 6 and 12 months of treatment. Seventy-one adverse events (AEs) including 2 serious AEs were observed, and 92 % of AEs were grade 1-2. Two patients discontinued the medication due to mild QTc prolongation. MRSS improved by a mean of 4.2 points (16 %) at 6 months and by 6.3 points (23 %) at 12 months in the 7 completers, p=0.02 and 0.01, respectively. Patients with a decrease in MRSS >20 % from baseline at 12 months (classified as improvers) had significantly higher expression of transforming growth factor beta receptor (TGFBR) and platelet derived growth factor receptor beta (PDGFRB) signaling genes at baseline than non improvers, and the expression of these genes significantly decreased in improvers post-treatment. CONCLUSION: Nilotinib was well tolerated by the majority of patients in this study, with tolerability limited primarily by mild QTc prolongation. Significant MRSS improvement was observed in these early, active patients, but is not conclusive of treatment effect given the open-label study design and small number of patients in this pilot study. Improvers had higher levels of expression of genes associated with TGFBR and PDGFRB signaling at baseline, and a significant decrease in the expression of these genes occurred only in patients with higher MRSS improvement. The findings of this pilot study warrant more conclusive evaluation. TRIAL REGISTRATION: Clinicaltrials.gov NCT01166139 , July 1, 2010. PMID- 26283633 TI - Efficacy of ultra-micronized palmitoylethanolamide in canine atopic dermatitis: an open-label multi-centre study. AB - BACKGROUND: Palmitoylethanolamide is a naturally occurring bioactive lipid, produced on-demand by damage-exposed cells. Palmitoylethanolamide is documented to counteract inflammation, itch and pain. OBJECTIVE: The aim of this 8-week study was to evaluate the efficacy of oral ultra-micronized palmitoylethanolamide (PEA-um) in dogs with moderate atopic dermatitis. ANIMALS: Clinicians from 39 veterinary clinics enrolled 160 dogs with nonseasonal atopic dermatitis and moderate pruritus. METHODS: This was a multi-centre open-label study. On days 0 (D0) and 56 (D56), owners evaluated pruritus with a Visual Analog Scale (VAS) and completed a validated Quality of Life (QoL) questionnaire. Veterinarians assessed the severity of skin lesions using the Canine Atopic Dermatitis Lesion Index (CADLI). RESULTS: Mean pruritus VAS score decreased from 5.7 +/- 0.08 cm (range 3.8-7.9 cm) to 3.63 +/- 0.19 cm (range 0.1-9.2 cm) (P < 0.0001). At D56, 58% of dogs showed a greater than 2 cm reduction from baseline and 30% showed an absent to-very mild pruritus (VAS <= 2 cm). Mean total CADLI at D56 decreased significantly (P < 0.0001); in 62% of dogs this score reached a value in the remission range (<=5). Mean total QoL score was significantly decreased (P < 0.0001) with 45% of dogs reaching QoL values described for healthy animals. Tolerability was good-to-excellent with only four dogs reporting treatment associated reversible adverse events. CONCLUSIONS AND CLINICAL IMPORTANCE: PEA-um appears to be effective and safe in reducing pruritus and skin lesions, and in improving QoL in dogs with moderate atopic dermatitis and moderate pruritus. PMID- 26283634 TI - Regulatory networks of non-coding RNAs in brown/beige adipogenesis. AB - BAT (brown adipose tissue) is specialized to burn fatty acids for heat generation and energy expenditure to defend against cold and obesity. Accumulating studies have demonstrated that manipulation of BAT activity through various strategies can regulate metabolic homoeostasis and lead to a healthy phenotype. Two classes of ncRNA (non-coding RNA), miRNA and lncRNA (long non-coding RNA), play crucial roles in gene regulation during tissue development and remodelling. In the present review, we summarize recent findings on regulatory role of distinct ncRNAs in brown/beige adipocytes, and discuss how these ncRNA regulatory networks contribute to brown/beige fat development, differentiation and function. We suggest that targeting ncRNAs could be an attractive approach to enhance BAT activity for protecting the body against obesity and its pathological consequences. PMID- 26283635 TI - Identification of miR-200a as a novel suppressor of connexin 43 in breast cancer cells. AB - Both miRNAs (miRs) and connexin 43 (Cx43) were important regulators of the metastasis of breast cancer, whereas the miRs regulating Cx43 expression in breast cancer cells were still obscure. In the present study, we scanned and found miR-1, miR-206, miR-200a, miR-381, miR-23a/b and miR-186 were functional suppressors of human Cx43 mRNA and protein expression. Specially, we demonstrated that only miR-200a could directly target the 3'-untranslated region (3'-UTR) of human Cx43 gene. Functionally, overexpression of Cx43 in MCF cells potentiated the migration activity, whereas additional miR-200a treatment notably prevented this effect. Finally, we demonstrated that decreased levels of miR-200a and elevated expression of Cx43 in the metastatic breast cancer tissues compared with the primary ones. Thus, we are the first to identify miR-200a as a novel and direct suppressor of human Cx43, indicating that miR200a/Cx43 axis might be a useful diagnostic and therapeutic target of metastatic breast cancer. PMID- 26283636 TI - Cohort Profile: The EDEN mother-child cohort on the prenatal and early postnatal determinants of child health and development. PMID- 26283637 TI - Relationship between arsenic-containing drinking water and skin cancers in the arseniasis endemic areas in Taiwan. AB - Artesian well-water had high concentrations of arsenic that led to the well-known black foot disease in Taiwan around the 1950s, and the associated cancers including skin cancer, bladder cancers and lung cancers. We sought to estimate the standardized morbidity ratio (SMR) and age-standardized incidence rate (ASIR) of cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in the black foot disease endemic areas (BFDEA) in Taiwan. A nationwide retrospective population-based survey was done with the data from the National Taiwan Cancer Registry Center between 1979 and 2007. Among the 29-year period, there were 11 191 cases with SCC and 13 684 cases with BCC diagnosed pathologically. The incidence rates were 4-6-fold higher for SCC and 3-4-fold higher for BCC in the BFDEA compared with the rest of Taiwan. The SMR decreased after stopping arsenic containing well-water drinking in the 1970s. The arsenic level in the drinking water, amount of contaminated water intake, occupation and sun-exposure time were not documented. This is the first nationwide, population-based study that shows the relationship between arsenic intoxication and non-melanoma skin cancers (SCC and BCC) through comparing the data in people living in the BFDEA and non-BFDEA in Taiwan. PMID- 26283638 TI - Understanding and predicting suicidality using a combined genomic and clinical risk assessment approach. AB - Worldwide, one person dies every 40 seconds by suicide, a potentially preventable tragedy. A limiting step in our ability to intervene is the lack of objective, reliable predictors. We have previously provided proof of principle for the use of blood gene expression biomarkers to predict future hospitalizations due to suicidality, in male bipolar disorder participants. We now generalize the discovery, prioritization, validation, and testing of such markers across major psychiatric disorders (bipolar disorder, major depressive disorder, schizoaffective disorder, and schizophrenia) in male participants, to understand commonalities and differences. We used a powerful within-participant discovery approach to identify genes that change in expression between no suicidal ideation and high suicidal ideation states (n=37 participants out of a cohort of 217 psychiatric participants followed longitudinally). We then used a convergent functional genomics (CFG) approach with existing prior evidence in the field to prioritize the candidate biomarkers identified in the discovery step. Next, we validated the top biomarkers from the prioritization step for relevance to suicidal behavior, in a demographically matched cohort of suicide completers from the coroner's office (n=26). The biomarkers for suicidal ideation only are enriched for genes involved in neuronal connectivity and schizophrenia, the biomarkers also validated for suicidal behavior are enriched for genes involved in neuronal activity and mood. The 76 biomarkers that survived Bonferroni correction after validation for suicidal behavior map to biological pathways involved in immune and inflammatory response, mTOR signaling and growth factor regulation. mTOR signaling is necessary for the effects of the rapid-acting antidepressant agent ketamine, providing a novel biological rationale for its possible use in treating acute suicidality. Similarly, MAOB, a target of antidepressant inhibitors, was one of the increased biomarkers for suicidality. We also identified other potential therapeutic targets or biomarkers for drugs known to mitigate suicidality, such as omega-3 fatty acids, lithium and clozapine. Overall, 14% of the top candidate biomarkers also had evidence for involvement in psychological stress response, and 19% for involvement in programmed cell death/cellular suicide (apoptosis). It may be that in the face of adversity (stress), death mechanisms are turned on at a cellular (apoptosis) and organismal level. Finally, we tested the top increased and decreased biomarkers from the discovery for suicidal ideation (CADM1, CLIP4, DTNA, KIF2C), prioritization with CFG for prior evidence (SAT1, SKA2, SLC4A4), and validation for behavior in suicide completers (IL6, MBP, JUN, KLHDC3) steps in a completely independent test cohort of psychiatric participants for prediction of suicidal ideation (n=108), and in a future follow-up cohort of psychiatric participants (n=157) for prediction of psychiatric hospitalizations due to suicidality. The best individual biomarker across psychiatric diagnoses for predicting suicidal ideation was SLC4A4, with a receiver operating characteristic (ROC) area under the curve (AUC) of 72%. For bipolar disorder in particular, SLC4A4 predicted suicidal ideation with an AUC of 93%, and future hospitalizations with an AUC of 70%. SLC4A4 is involved in brain extracellular space pH regulation. Brain pH has been implicated in the pathophysiology of acute panic attacks. We also describe two new clinical information apps, one for affective state (simplified affective state scale, SASS) and one for suicide risk factors (Convergent Functional Information for Suicide, CFI-S), and how well they predict suicidal ideation across psychiatric diagnoses (AUC of 85% for SASS, AUC of 89% for CFI-S). We hypothesized a priori, based on our previous work, that the integration of the top biomarkers and the clinical information into a universal predictive measure (UP-Suicide) would show broad-spectrum predictive ability across psychiatric diagnoses. Indeed, the UP-Suicide was able to predict suicidal ideation across psychiatric diagnoses with an AUC of 92%. For bipolar disorder, it predicted suicidal ideation with an AUC of 98%, and future hospitalizations with an AUC of 94%. Of note, both types of tests we developed (blood biomarkers and clinical information apps) do not require asking the individual assessed if they have thoughts of suicide, as individuals who are truly suicidal often do not share that information with clinicians. We propose that the widespread use of such risk prediction tests as part of routine or targeted healthcare assessments will lead to early disease interception followed by preventive lifestyle modifications and proactive treatment. PMID- 26283640 TI - Reciprocal causation models of cognitive vs volumetric cerebral intermediate phenotypes for schizophrenia in a pan-European twin cohort. PMID- 26283639 TI - A pilot in vivo proton magnetic resonance spectroscopy study of amino acid neurotransmitter response to ketamine treatment of major depressive disorder. AB - The N-methyl-D-aspartate receptor antagonist ketamine can improve major depressive disorder (MDD) within hours. To evaluate the putative role of glutamatergic and GABAergic systems in ketamine's antidepressant action, medial prefrontal cortical (mPFC) levels of glutamate+glutamine (Glx) and gamma aminobutyric acid (GABA) were measured before, during, and after ketamine administration using proton magnetic resonance spectroscopy. Ketamine (0.5 mg kg( 1) intravenously) was administered to 11 depressed patients with MDD. Glx and GABA mPFC responses were measured as ratios relative to unsuppressed voxel tissue water (W) successfully in 8/11 patients. Ten of 11 patients remitted (50% reduction in 24-item Hamilton Depression Rating Scale and total score ?10) within 230 min of commencing ketamine. mPFC Glx/W and GABA/W peaked at 37.8%+/-7.5% and 38.0%+/-9.1% above baseline in ~26 min. Mean areas under the curve for Glx/W (P=0.025) and GABA/W (P=0.005) increased and correlated (r=0.796; P=0.018). Clinical improvement correlated with 90-min norketamine concentration (df=6, r= 0.78, P=0.023), but no other measures. PMID- 26283641 TI - Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium. PMID- 26283643 TI - Subretinal versus intravitreal injection of recombinant tissue plasminogen activator in post-traumatic submacular haemorrhages. PMID- 26283642 TI - Acute experimental changes in mood state regulate immune function in relation to central opioid neurotransmission: a model of human CNS-peripheral inflammatory interaction. AB - Although evidence shows depressed moods enhance risk for somatic diseases, molecular mechanisms underlying enhanced somatic susceptibility are ill-defined. Knowledge of these molecular mechanisms will inform development of treatment and prevention strategies across comorbid depressive and somatic illnesses. Existing evidence suggests that interleukin-18 (IL-18; an IL-1 family cytokine) is elevated in depression and implicated in pathophysiology underlying comorbid medical illnesses. We previously identified strong associations between baseline IL-18 and MU-opioid receptor availability in major depressive disorder (MDD) volunteers. Combined with the evidence in animal models, we hypothesized that experimental mood induction would change IL-18, the extent proportional to opioid neurotransmitter release. Using the Velten technique in a [(11)C]carfentanil positron emission tomography neuroimaging study, we examined the impact of experimentally induced mood (sad, neutral) on plasma IL-18 and relationships with concurrent changes in the central opioid neurotransmission in 28 volunteers (healthy, MDD). Results showed mood induction impacted IL-18 (F2,25=12.2, P<0.001), sadness increasing IL-18 (T27=2.6, P=0.01) and neutral mood reducing IL 18 (T27=-4.1, P<0.001). In depressed volunteers, changes in IL-18 were more pronounced (F2,25=3.6, P=0.03) and linearly proportional to sadness-induced MU opioid activation (left ventral pallidum, bilateral anterior cingulate cortices, right hypothalamus and bilateral amygdala). These data demonstrate that dynamic changes of a pro-inflammatory IL-1 superfamily cytokine, IL-18, and its relationship to MU-opioid neurotransmission in response to experimentally induced sadness. Further testing is warranted to delineate the role of neuroimmune interactions involving IL-18 in enhancing susceptibility to medical illness (that is, diabetes, heart disease and persistent pain states) in depressed individuals. PMID- 26283644 TI - Effect of coronal flaring on apical extrusion of debris during root canal instrumentation using single-file systems. AB - AIM: To evaluate the effect of coronal flaring on the amount of debris extruded apically during root canal preparation using the Reciproc, WaveOne (WO) and OneShape (OS) single-file systems. METHODOLOGY: Ninety extracted single-rooted mandibular incisor teeth were randomly assigned to six groups (n = 15 for each group) for canal instrumentation. Endodontic access cavities were prepared in each tooth. In three of the six groups, coronal flaring was not performed; coronal flaring was performed with Gates-Glidden drills on all teeth in the remaining three groups. The canals were then instrumented with one or other of the following single-file instrument systems: Reciproc, WO and OS. Debris extruded apically during instrumentation was collected into pre-weighed Eppendorf tubes. The tubes were then stored in an incubator at 70 degrees C for 5 days. The weight of the dry extruded debris was established by subtracting the pre instrumentation and post-instrumentation weight of the Eppendorf tubes for each group. Data were analysed using one-way analysis of variance (anova) and Tukey's post hoc tests (P = 0.05). RESULTS: Reciproc and WO files without coronal flaring produced significantly more debris compared with the other groups (P < 0.05). There was no significant difference in apical extrusion of debris amongst the other groups (P > 0.05). CONCLUSIONS: All single-file systems caused apical extrusion of debris. Performing coronal flaring prior to canal preparation reduced the amount of apically extruded debris when using Reciproc or WO systems. PMID- 26283645 TI - The professional humanitarian and the downsides of professionalisation. AB - Criticisms lodged at humanitarian relief often include the belief that professionalisation is needed. The problems associated with humanitarianism would end, it is assumed, if the delivery of aid, and relief workers themselves, were more professional and 'business like'. To explore this further, the paper asks what comprises a profession, and offers four criteria: (1) specialisation of knowledge; (2) establishment of the profession as a livelihood; (3) organisation and institutionalisation; and (4) legitimacy and authority. A model for understanding professionalisation, as developed by the author, is then presented. The analysis compares six other professions against the same criteria to argue that the humanitarian community already constitutes a profession. Finally, three potential downsides of professionalisation are offered: the distance of the relief worker from the beneficiary, barriers to entry into the humanitarian sector, and adding to risk aversion and a decline in innovation. Based on these findings, professionalisation should be approached with some caution. PMID- 26283646 TI - High-Pressure Synthesis of Boron-Doped Ultrasmall Diamonds from an Organic Compound. AB - The first application of the high-pressure-high-temperature (HPHT) technique for direct production of doped ultrasmall diamonds starting from a one-component organic precursor is reported. Heavily boron-doped diamond nanoparticles with a size below 10 nm are produced by HPHT treatment of 9-borabicyclo [3,3,1]nonane dimer molecules. PMID- 26283647 TI - Recovery of calf muscle endurance 3 months after an Achilles tendon rupture. AB - The purpose of this study was to evaluate calf muscle endurance in a seated position 3 months after an Achilles tendon rupture and to evaluate how the ability to perform standardized seated heel-rises correlated to the single-leg standing heel-rise test and to patient-reported symptoms evaluated with the Achilles tendon Total Rupture Score (ATRS) 3 and 6 months after the injury. Ninety-three patients were included from a cohort of 101 patients participating in a prospective, randomized controlled trial comparing surgical and nonsurgical treatment after Achilles tendon rupture. Forty-seven patients were treated surgically and 46 nonsurgically. Ninety-one patients out of 93 (98%) could perform the standardized seated heel-rises. At the 3-month follow-up, there was a significant difference (P < 0.001) between the injured and the healthy side performing standardized seated heel-rises. There were also significant correlations (r = 0.29-0.37, P = < 0.05) between the standardized seated heel rises and ATRS 3 and 6 months after injury in the group who could not perform single-leg standing heel-rises. There were no significant differences between the surgical and nonsurgical treatment groups. The evaluation of standardized seated heel-rises appears to be a useful tool to quantify progress and predict future functional performance and patient-reported symptoms. PMID- 26283648 TI - Disseminated specific cutaneous infiltrates of B-cell chronic lymphocytic leukemia - Wolf's isotopic response following herpes zoster infection. PMID- 26283649 TI - High diversity of viable bacteria isolated from lymph nodes of slaughter pigs and its possible impacts for food safety. AB - AIMS: Ileocaecal lymph nodes (ICLNs) of pigs, the key immune inductive site for bacterial systemic invasion, were examined in this study with emphasis on viable and cultivable bacteria. METHODS AND RESULTS: Asymptomatic and pathologically altered ICLNs of slaughter pigs (n = 16) with hyperplasia, purulence or granulomatous formations were aerobically and anaerobically cultivated. In total, 209 isolates were collected and the near full-length 16S rRNA gene from each isolate was sequenced. Taxonomic classification revealed that 68% of the isolates belonged to Proteobacteria, 27% to Firmicutes and 5% to Actinobacteria. Purulent and granulomatous ICLNs generally tended to contain more Proteobacteria than asymptomatic and enlarged ICLNs (P = 0.061). The isolates could be assigned to 25 species belonging to 17 genera including Escherichia, Carnobacterium, Lactobacillus, Staphylococcus and Acinetobacter. Furthermore, pathogens such as Streptococcus suis and Salmonella enterica were detected. The most abundant isolate (57%) was most similar (>99%) to Escherichia coli. Random amplified polymorphic DNA (RAPD) profiling revealed a high genetic diversity among E. coli isolates and 24% of these isolates were positive for at least one gene associated with enterohemorrhagic disease (eae, fliC, stx1 or hlyA). Compared with a recently published DNA-based high-throughput sequencing data set including the same ICLNs, 4% of species detected were cultivable. CONCLUSIONS: The presence of viable, commensal and pathogenic bacterial phylotypes could be proven in ICLNs with Proteobacteria being dominant. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study that broadly characterizes viable bacteria from ICLNs of pigs. The presence of bacteria in lymph nodes of farm animals has practical relevance for host colonization and possible chronic infection. It is also of great interest for basic research investigating translocation of bacteria from the gastrointestinal tract to ICLNs. PMID- 26283650 TI - Commentary on: The Effect of Hering's Law on Different Ptosis Repair Methods. PMID- 26283651 TI - Commentary on: Safety of Cosmetic Procedures in Elderly and Octogenarian Patients. PMID- 26283652 TI - Educational level and risk profile and risk control in patients with coronary heart disease. AB - BACKGROUND: The purpose of this study was to ascertain way in which conventional risk factors, readiness to modify behaviour and to comply with recommended medication, and the effect of this medication were associated with education in patients with established coronary heart disease (CHD). METHODS: The EUROASPIRE IV (EUROpean Action on Secondary Prevention by Intervention to Reduce Events) study was a cross-sectional survey undertaken in 24 European countries to ascertain how recommendations on secondary CHD prevention are being followed in clinical practice. Consecutive patients, men and women <=80 years of age who had been hospitalized for an acute coronary syndrome or revascularization procedure, were identified retrospectively. Data were collected through an interview with examinations at least six months and no later than three years after hospitalization. RESULTS: A total of 7937 patients (1934 (24.37%) women) were evaluated. Patients with primary education were older, with a larger proportion of women. Control of risk factors, as defined by Joint European Societies 4 and 5 guidelines, was significantly better with higher education for current smoking (p = 0.001), overweight and obesity (p = 0.047 and p = 0.029, respectively), low physical activity (p < 0.001) and low high-density lipoprotein (HDL)-cholesterol (p = 0.011) in men, and for obesity (p = 0.005), high blood pressure (p < 0.005 and p < 0.001), low physical activity (p = 0.001), diabetes (p < 0.001) and low HDL-cholesterol (p = 0.023) in women. Patients with primary and secondary education were more often treated with diuretics and antidiabetic drugs. Better control of hypertension was achieved in patients with higher education. CONCLUSION: Particular risk communication and control are needed in secondary CHD prevention for patients with lower educational status. PMID- 26283653 TI - Cancer Metastases: So Close and So Far. AB - Metastases are tumors that develop at a distance from their primary origin and are responsible for the death of 90% of cancer patients. For over a century the notion of seed (migrating cells) and soil (the locus where those cells anchor) provided an accurate account of which were the protagonists in their genesis. Despite aggressive efforts to unravel the dynamics involving migrating cells and the niche in which they anchor, explanations of this process remain ill-defined and controversial. The controversy is generated by the different premises that researchers adopt to integrate the vast amount of data collected at different levels of biological organization. The so-far hegemonic theory of cancer and its metastases has been the somatic mutation theory (SMT) and a number of its variants: They consider that cancers and their metastases represent a cell-based, genetic and molecular disease. This interpretation has been challenged by the tissue organization field theory (TOFT), which considers instead that cancer is a tissue-based disease, akin to development gone awry. In this Commentary, the merits of both theories are compared now in the context of metastases. Based on the epistemological shortcomings of the SMT and the acknowledged failure of therapeutic approaches based on this theory, we conclude that TOFT explains comprehensibly carcinogenesis and the appearance of metastases. PMID- 26283654 TI - Essential medicines for breast cancer in low and middle income countries. AB - BACKGROUND: Breast cancer is the most common type of cancer among women worldwide. In low and middle-income countries (LMICs), appropriate selection of medicines on national essential medicines lists (NEMLs) is a first step towards adequate access to treatment. We studied selection of systemic treatments for breast cancer on NEMLs and assessed its alignment with treatment guidelines for different types of early and advanced breast cancer. Furthermore, influence of country characteristics on the selection was investigated. METHOD: NEMLs from 75 LMICs were studied for inclusion of all components of therapy in each stage of breast cancer according to international consensus guidelines. The results were then grouped by income level, WHO region and the NEMLs' release date. Non parametric tests were used for statistical analysis. RESULTS: Unlike HER2 targeted therapies (<10%), aromatase inhibitors (12%) and taxanes (28%); tamoxifen and first generation chemotherapeutic regimens (e.g., anthracycline based regimens) were frequently found in the NEMLs (71-78%). Consequently, all components of treatment for "Luminal A" early breast cancer and non HER2 overexpressed advanced breast cancer were found on the NEMLs of over 70% of countries. However, 40% of the low income countries did not have all the components of therapy for any type of early breast cancer in their NEMLs, and adequate treatment of HER2 overexpressed breast cancer was hardly possible with the current selections. Recent NEMLs were more aligned with the guidelines (p < 0.05). Eastern Mediterranean and African regions less frequently incorporated all components of breast cancer treatment in their NEMLs. CONCLUSION: Alignment of selection with guidelines' recommendations was inconsistent for different types of early and advanced breast cancer in NEMLs. Regular updates and more attention to clinical guidelines is therefore recommended. PMID- 26283656 TI - Hidden genes in birds. AB - We report that a subset of avian genes is characterized by very high GC content and long G/C stretches. These sequence characteristics correlate with the frequent absence of these genes from genomic databases. We provide several examples where genes in this subset are mistakenly reported as missing in birds. www.dx.doi.org/10.1186/s13059-015-0725-y. PMID- 26283655 TI - Cryoballoon Versus Open Irrigated Radiofrequency Ablation in Patients With Paroxysmal Atrial Fibrillation: The Prospective, Randomized, Controlled, Noninferiority FreezeAF Study. AB - BACKGROUND: There is a lack of data on the comparative efficacy and procedural safety of open irrigated radiofrequency (RF) and cryoballoon catheter (CB) ablation for pulmonary vein isolation in patients with paroxysmal atrial fibrillation. METHODS AND RESULTS: In a prospective, noninferiority study, 315 patients were randomly assigned to RF (n=159) or CB (n=156) ablation. The primary end point was freedom from atrial arrhythmia with absence of persistent complications. Patients were largely comparable between groups with more vascular disease in the RF group (8.2% versus 2.6% for CB; P=0.028). The primary end point at 12 months was achieved by 70.7% with RF and 73.6% with CB (multiple procedure success), including 31 redo procedures in each group (19.5% of RF versus 19.9% of CB; P=0.933). For the intention-to-treat population, noninferiority of CB was revealed for the predefined inferiority margin (risk difference, 0.029; 95% confidence interval, -0.074 to 0.132; P<0.001). Rates at 6 months were 63.1% and 64.1% for the RF and CB groups (single procedure success), and noninferiority was confirmed (risk difference, 0.010; 95% confidence interval, -0.097 to 0.116; P=0.002). Periprocedural complications for the index procedure were more frequent in the CB group (5.0% RF, 12.2% CB; P=0.022) with a significant difference in phrenic nerve palsies (0% RF, 5.8% CB; P=0.002). CONCLUSION: This large, prospective, randomized, controlled study demonstrates noninferiority of CB ablation versus RF ablation for treating patients with paroxysmal atrial fibrillation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00774566. PMID- 26283657 TI - Plasma n-3 fatty acids and clinical outcomes in recent-onset rheumatoid arthritis. AB - A randomised controlled trial (RCT) of high-dose v. low-dose fish oil in recent onset rheumatoid arthritis (RA) demonstrated that the group allocated to high dose fish oil had increased remission and decreased failure of disease-modifying anti-rheumatic drug (DMARD) therapy. This study examines the relationships between plasma phospholipid levels of the n-3 fatty acids in fish oil, EPA and DHA, and remission and DMARD use in recent-onset RA. EPA and DHA were measured in blood samples from both groups of the RCT. The data were analysed as a single cohort, and Cox proportional hazards models were used to examine relationships between plasma phospholipid (PL) EPA and DHA and various outcome measures. When analysed as a single cohort, plasma PL EPA was related to time to remission, with a one unit increase in EPA (1% total fatty acids) associated with a 12% increase in the probability of remission at any time during the study period (hazard ratio (HR)=1.12; 95% CI 1.02, 1.23; P=0.02). Adjustment for smoking, anti-cyclic citrullinated peptide antibodies and 'shared epitope' HLA-DR allele status did not change the HR. Plasma PL EPA, adjusted for the same variables, was negatively related to time to DMARD failure (HR=0.85; 95% CI 0.72, 0.99; P=0.047). The HR for DHA and time to remission or DMARD failure were similar in magnitude to those for EPA, but not statistically significant. Biomarkers of n-3 status, such as plasma PL EPA, have the potential to predict clinical outcomes relevant to standard drug treatment of RA patients. PMID- 26283658 TI - Recruitment of dorsal midbrain catecholaminergic pathways in the recovery from nerve injury evoked disabilities. AB - BACKGROUND: The periaqueductal gray region (PAG) is one of several brain areas identified to be vulnerable to structural and functional change following peripheral nerve injury. Sciatic nerve constriction injury (CCI) triggers neuropathic pain and three distinct profiles of changes in complex behaviours, which include altered social and sleep-wake behaviours as well as changes in endocrine function. The PAG encompasses subgroups of the A10 dopaminergic and A6 noradrenergic cell groups; the origins of significant ascending projections to hypothalamic and forebrain regions, which regulate sleep, complex behaviours and endocrine function. We used RT-PCR, western blots and immunohistochemistry for tyrosine hydroxylase to determine whether (1) tyrosine hydroxylase increased in the A10/A6 cells and/or; (2) de novo synthesis of tyrosine hydroxylase, in a 'TH naive' population of ventral PAG neurons characterized rats with distinct patterns of behavioural and endocrine change co-morbid with CCI evoked-pain. RESULTS: Evidence for increased tyrosine hydroxylase transcription and translation in the constitutive A10/A6 cells was found in the midbrain of rats that showed an initial 2-3 day post-CCI, behavioural and endocrine change, which recovered by days 5-6 post-CCI. Furthermore these rats showed significant increases in the density of TH-IR fibres in the vPAG. CONCLUSIONS: Our data provide evidence for: (1) potential increases in dopamine and noradrenaline synthesis in vPAG cells; and (2) increased catecholaminergic drive on vPAG neurons in rats in which transient changes in social behavior are seen following CCI. The data suggests a role for dopaminergic and noradrenergic outputs, and catecholaminergic inputs of the vPAG in the expression of one of the profiles of behavioural and endocrine change triggered by nerve injury. PMID- 26283660 TI - Implementation of an evidence-based seizure algorithm in intellectual disability nursing: A pilot study. AB - Based on the results of the Surrogate Decision-Making Self Efficacy Scale (Lopez, 2009a), this study sought to determine whether nurses working in the field of intellectual disability (ID) experience increased confidence when they implemented the American Association of Neuroscience Nurses (AANN) Seizure Algorithm during telephone triage. The results of the study indicated using the AANN Seizure Algorithm increased self-confidence for many of the nurses in guiding care decisions during telephone triage. The treatment effect was statistically significant -3.169(p < 0.01) for a small sample of study participants. This increase in confidence is clinically essential for two reasons. Many individuals with ID and epilepsy reside within community-based settings. ID nurses provide seizure guidance to this population living in community-based settings via telephone triage. Evidenced-based training tools provide a valuable mechanism by guiding nurses via best practices. Nurses may need to be formally trained for seizure management due to high epilepsy rates in this population. PMID- 26283659 TI - Hydrogen sulphide and mild hypothermia activate the CREB signaling pathway and prevent ischemia-reperfusion injury. AB - BACKGROUND: Both hydrogen sulphide (H2S) and mild hypothermia have been reported to prevent brain damage caused by reperfusion assault through regulating the N methyl-D-aspartate receptor (NMDAR). However, the relationship between the two treatments and how they exert neuro-protective effects through NMDARs remain to be elucidated. METHODS: Transient cerebral ischemia was induced using the Pulsinelli four-vessel occlusion method. We used sodium hydrosulphide (NaHS) as the H2S donor. We randomly divided 100 Sprague-Dawley rats into five groups of 20: Sham operation group (Sh), normothermic (36-37 degrees C) ischemia group (NT), mild hypothermic (32-33 degrees C) ischemia group (mHT), normothermic ischemia combined with NaHS treatment group (NT + NaHS), and mild hypothermic ischemia combined with NaHS treatment group (mHT + NaHS). After 6 hrs of reperfusion, rats were decapitated and hippocampus samples were immediately collected. We measured NR2A (GluN1), NR2B (GluN2) and p-CREB protein levels using western blotting. We further analyzed BDNF mRNA expression by real-time PCR. Hematoxylin and eosin (HE) staining was used to examine pyramidal cell histology at the CA1 region. All statistical analyses were carried out by ANOVA and LSD t test as implemented by the SPSS 13.0 software. RESULTS: In the four test groups with ischemia-reperfusion, hippocampal H2S concentration increased following treatment, and administration of NaHS further increased H2S levels. Moreover, administration of both NaHS and mild hypothermia resulted in up-regulation of NR2A and NR2B protein expressions, as well as p-CREB protein and BDNF mRNA levels. At the cellular level, NaHS and mild hypothermia groups exhibited lower damage caused by ischemia-reperfusion in the CA1 region of the hippocampus. The strongest protective effect was observed in rats treated with combined NaHS and mild hypothermia, suggesting their effects were additive. CONCLUSION: Our results support previous findings that hydrogen sulphide and mild hypothermia can prevent ischemia-reperfusion injury. Both treatments caused an up-regulation of NMDA receptors, as well as an elevation in p-CREB protein and BDNF mRNA levels. Thus, hydrogen sulphide and mild hypothermia may provide neuro-protective effect through activating the pro-survival CREB signaling pathway. PMID- 26283661 TI - Teachers' interpersonal style and its relationship to emotions, causal attributions, and type of challenging behaviors displayed by students with intellectual disabilities. AB - Teachers' interpersonal style is a new field of research in the study of students with intellectual disabilities and challenging behaviors in school context. In the present study, we investigate emotions and causal attributions of three basic types of challenging behaviors: aggression, stereotypy, and self-injury, in relation to teachers' interpersonal style. One hundred and seventy seven Greek general and special educator teachers participated in the study by completing a three-scaled questionnaire. Statistical analysis revealed that the type of challenging behaviors affected causal attributions. According to regression analysis, emotions, teaching experience, expertise in special education, and gender explained a significant amount of variance in interpersonal style. Emotions were found to have a mediating role in the relationship between causal attributions and interpersonal style of "willingness to support," when challenging behaviors were attributed to stable causes or causes under the control of the individual with intellectual disabilities. PMID- 26283662 TI - Childhood sexual abuse experiences and its associated factors among adolescent female high school students in Arbaminch town, Gammo Goffa zone, Southern Ethiopia: a mixed method study. AB - BACKGROUND: Childhood sexual abuse is a major social problem in Africa including Ethiopia. Moreover, little has been explored about the pattern of childhood sexual abuse in the context of high school students in Ethiopia in general and in Arbaminch town in particular. Thus, the present study aims to assess the prevalence and associated factors of childhood sexual abuse among adolescent female high school students in Arbaminch town. METHODS: A school- based, cross sectional study was conducted among adolescent female high school students in Arbaminch town from 3(rd) to 8(th) March 2014. Both quantitative and qualitative methods of data collection were used. For the quantitative data, a simple random sampling technique was used to select 369 female students from grade ten of the six high schools. A pre-tested, self-administered questionnaire was used to collect the data and then analysis was made using SPSS version 20 statistical packages. For the qualitative component, fourteen in-depth interviews were conducted and analysed based on the thematic areas. RESULT: The prevalence of life time rape among adolescent female high school students in Arbaminch town was 11 %. The odds of experiencing life time rape was higher among students who lived alone (AOR = 4.30; 95 % CI: 1.81, 10.24) and among students who lived with their friends (AOR = 3.31; 95 % CI: 1.23, 8.89) than those lived with their parents. The chance of experiencing rape among students who have had no open discussions with their parents about sexuality and reproductive health was higher (AOR = 2.93; 95 % CI: 1.33, 6.45) than those who have had discussions. CONCLUSION: This study revealed high levels of childhood sexual abuse among the adolescent female high school students in Arbaminch town. Ever having a discussion about sexuality and reproductive health with parents, living arrangement of the student, and father's educational status had statistically significant association with childhood sexual abuse. Unwanted pregnancy and abortion were the most common reproductive outcomes of rape. Comprehensive school based reproductive health education, community based awareness creation, open discussions about sexuality and reproductive health matters with students at family level are recommended. PMID- 26283663 TI - Vitamin D3 supplementation in HIV infection: effectiveness and associations with antiretroviral therapy. AB - BACKGROUND: HIV infection and antiretroviral therapy (ART) may create unique risk factors for vitamin D insufficiency, including alterations of vitamin D metabolism by ART. We prospectively compared demographic and clinical parameters between vitamin D sufficient and insufficient HIV-infected (HIV+) adults, and assessed changes in these parameters among insufficient participants following standardized vitamin D supplementation. METHODS: HIV+ adults (>= 18 years old) with HIV-1 RNA <50 copies/mL on ART were enrolled. Vitamin D sufficiency and insufficiency were defined as 25-hydroxyvitamin D (25(OH)D) >= 30 or <30 ng/mL, respectively. Insufficient participants received open-label vitamin D3 50,000 IU twice weekly for 5 weeks, then 8000 IU twice weekly to complete 24 weeks. The primary endpoint was success or failure to achieve 25(OH)D >= 30 ng/mL at week 24. RESULTS: Ninety-seven participants enrolled (34 vitamin D sufficient, 63 insufficient); 32% female, 47% non-White, median age 46 years, ART duration 5 years, CD4+ T lymphocyte count (CD4) 673 cells/mm(3). 25(OH)D repletion was 83% (95% CI 71%-90%) successful. 25(OH)D levels correlated with both CD4 (r = 0.44, p = 0.01) and time on protease inhibitor (r = -0.35, p = 0.01). After adjusting for age, sex, race, nadir CD4 and baseline 25(OH)D: 1) current use of efavirenz exposure was associated with a 21.1 ng/mL higher week 24 25(OH)D level (p = 0.007), 2) per year use of zidovudine was associated with 7.1 ng/mL reduction in week 24 serum 25(OH)D (p = 0.05) and 3) every 1 ng/mL 25(OH)D increase was associated with a 3.3 cell/mm(3) CD4 increase (p = 0.06). CONCLUSION: Vitamin D3 supplementation was effective in repleting 25(OH)D levels after 24 weeks. Current efavirenz use was positively associated with post-repletion 25(OH)D levels, while greater time on zidovudine was associated with lower post-repletion 25(OH)D levels. The association between improved CD4 recovery and vitamin D repletion suggests a potential benefit of vitamin D supplementation on immunologic recovery during HIV treatment. TRIAL REGISTRATION: This trial is registered at The Brazilian Clinical Trials Registry (U1111-1165-2537). PMID- 26283665 TI - Cardiac hemodynamic response to the 6-minute walk test in young adults and the elderly. AB - BACKGROUND: Exercise capacity is evaluated using the 6-minute walk test in various diseases. Variety in the distances walked was also shown in healthy subjects. Moreover, age-related influences on cardiac hemodynamic response to the 6-minute walk test have not been clarified. The purpose of this study was thus to investigate the hemodynamic response to the 6-minute walk test and to detect factors related to the distance walked in healthy subjects. METHODS: Thirteen young adults (age 20.5 +/- 0.7 years, BMI 22.0 +/- 4.3) and 26 elderly individuals (age 60.2 +/- 6.1 years, BMI 21.7 +/- 2.2) were enrolled to measure real-time hemodynamic responses using non-invasive impedance cardiography during the 6-minute walk test. RESULTS: Stroke volume was higher in the young than in the elderly and reached a plateau within 30 s of starting to walk in all subjects. An increase in heart rate took more than 1 min in the elderly, while it took less than 30 s in the young, which resulted in slower increases in cardiac output and cardiac index in the elderly. There was no difference in the distance in the 6-minute walk test between the young and the elderly. The distance walked was correlated with heart rate, cardiac output, and cardiac index, but not with stroke volume, at the end of the 6-minute walk test. CONCLUSIONS: The distance walked appeared to depend on increased cardiac output based on heart rate, but did not appear to be limited by stroke volume, in healthy subjects. PMID- 26283664 TI - Increased Fab thermoresistance via VH-targeted directed evolution. AB - Antibody aggregation is frequently mediated by the complementarity determining regions within the variable domains and can significantly decrease purification yields, shorten shelf-life and increase the risk of anti-drug immune responses. Aggregation-resistant antibodies could offset these risks; accordingly, we have developed a directed evolution strategy to improve Fab stability. A Fab-phage display vector was constructed and the VH domain targeted for mutagenesis by error-prone PCR. To enrich for thermoresistant clones, the resulting phage library was transiently heated, followed by selection for binding to an anti light chain constant domain antibody. Five unique variants were identified, each possessing one to three amino acid substitutions. Each engineered Fab possessed higher, Escherichia coli expression yield, a 2-3 degrees C increase in apparent melting temperature and improved aggregation resistance upon heating at high concentration. Select mutations were combined and shown to confer additive improvements to these biophysical characteristics. Finally, the wild-type and most stable triple variant Fab variant were converted into a human IgG1 and expressed in mammalian cells. Both expression level and aggregation resistance were similarly improved in the engineered IgG1. Analysis of the wild-type Fab crystal structure provided a structural rationale for the selected residues changes. This approach can help guide future Fab stabilization efforts. PMID- 26283666 TI - Self-referral psychological treatment centre for young adults: a 2-year observational evaluation of routine practice before and after treatment. AB - OBJECTIVES: To examine a self-referral psychological service provided to young adults with regard to effects on anxiety, depression and psychological distress and to explore client factors predicting non-adherence and non-response. DESIGN: Observational study over a 2-year period. SETTING: Young Adults Centre providing psychological services by self-referral (preprimary care) to Linkoping, Atvidaberg, and Kinda municipalities (combined population 145,000) in Ostergotland county, Sweden. PARTICIPANTS: 607 young adults (16-25 years of age); 71% females (n=429). INTERVENTION: Individually scheduled cognitive behavioural therapy delivered in up to six 45 min sessions structured according to an assessment of the client's mental health problems: anxiety, depression, anxiety and depression combined, or decreased distress without specific anxiety or depression. PRIMARY OUTCOME MEASURES: Pre-post intervention changes in psychological distress (General Health Questionnaire-12, GHQ-12), Hospital Anxiety and Depression Scale Anxiety/Depression (HADS-A/D). RESULTS: 192 clients (32.5%) discontinued the intervention on their own initiative and 39 clients (6.6%) were referred to a psychiatric clinic during the course of the intervention. Intention-to-treat analyses including all clients showed a medium treatment effect size (d=0.64) with regard to psychological distress, and small effect sizes were observed with regard to anxiety (d=0.58) and depression (d=0.57). Restricting the analyses to clients who adhered to the agreed programme, a large effect size (d=1.26) was observed with regard to psychological distress, and medium effect sizes were observed with regard to anxiety (d=1.18) and depression (d=1.19). Lower age and a high initial HADS-A score were the strongest risk factors for non-adherence, and inability to concentrate and thinking of oneself as a worthless person increased the risk for discontinuation. CONCLUSIONS: We conclude that provision of psychological services to young people through a self-referral centre has potential to improve long-term mental health in communities, but management of non-adherence remains a central challenge. PMID- 26283668 TI - Paracetamol for the treatment of patent ductus arteriosus in preterm neonates: a systematic review and meta-analysis. AB - OBJECTIVES: We performed a systematic review and meta-analysis of all the available evidence to assess the efficacy and safety of paracetamol for the treatment of patent ductus arteriosus (PDA) in neonates, and to explore the effects of clinical variables on the risk of closure. DATA SOURCE: MEDLINE, Scopus and ISI Web of Knowledge databases, using the following medical subject headings and terms: paracetamol, acetaminophen and patent ductus arteriosus. Electronic and manual screening of conference abstracts from international meetings of relevant organisations. Manual search of the reference lists of all eligible articles. STUDY SELECTION: Studies comparing paracetamol versus ibuprofen, indomethacin, placebo or no intervention for the treatment of PDA. DATA EXTRACTION: Data regarding efficacy and safety were collected and analysed. RESULTS: Sixteen studies were included: 2 randomised controlled trials (RCTs) and 14 uncontrolled studies. Quality of selected studies is poor. A meta-analysis of RCTs does not demonstrate any difference in the risk of ductal closure (Mantel Haenszel model, RR 1.07, 95% CI 0.87 to 1.33 and RR 1.03, 95% CI 0.92 to 1.16, after 3 and 6 days of treatment, respectively). Proportion meta-analysis of uncontrolled studies demonstrates a pooled ductal closure rate of 49% (95% CI 29% to 69%) and 76% (95% CI 61% to 88%) after 3 and 6 days of treatment with paracetamol, respectively. Safety profiles of paracetamol and ibuprofen are similar. CONCLUSIONS: Efficacy and safety of paracetamol appear to be comparable with those of ibuprofen. These results should be interpreted with caution, taking into account the non-optimal quality of the studies analysed and the limited number of neonates treated with paracetamol so far. PMID- 26283670 TI - Time to eradication of Mycoplasma genitalium after antibiotic treatment in men and women. AB - OBJECTIVES: The objectives of this study were to evaluate the time to a Mycoplasma genitalium-negative test after start of treatment and to monitor if and when antibiotic resistance developed. METHODS: Sexually transmitted disease (STD) clinic attendees with suspected or verified M. genitalium infection were treated with azithromycin (5 days, 1.5 g; n = 85) or moxifloxacin (n = 5). Subjects with symptomatic urethritis or cervicitis of unknown aetiology were randomized to either doxycycline (n = 49) or 1 g of azithromycin as a single dose (n = 51). Women collected vaginal specimens and men collected first-catch urine 12 times during 4 weeks. Specimens were tested for M. genitalium with a quantitative MgPa PCR and for macrolide resistance-mediating mutations with a PCR targeting 23S rRNA. CLINICAL TRIALS REGISTRATION: NCT01661985. RESULTS: Ninety M. genitalium cases were enrolled. Of 56 patients with macrolide-susceptible strains before treatment with azithromycin (1.5 g, n = 46; 1 g single oral dose, n = 10), 54 (96%) had a negative PCR test within 8 days. In four patients, M. genitalium converted from macrolide susceptible to resistant after a 10 day lag time with negative tests (azithromycin 1.5 g, n = 3; 1 g single oral dose, n = 1). Moxifloxacin-treated subjects (n = 4) were PCR negative within 1 week. Six of eight (75%) remained positive despite doxycycline treatment. CONCLUSIONS: PCR for M. genitalium rapidly became negative after azithromycin treatment. Macrolide resistant strains were detected after initially negative tests. Test of cure should be recommended no earlier than 3-4 weeks. PMID- 26283669 TI - Hypoglycaemia and hyperglycaemia are associated with unfavourable outcome in infants with hypoxic ischaemic encephalopathy: a post hoc analysis of the CoolCap Study. AB - OBJECTIVE: To investigate the association of neonatal hypoglycaemia and hyperglycaemia with outcomes in infants with hypoxic ischaemic encephalopathy (HIE). DESIGN: Post hoc analysis of the CoolCap Study. SETTING: 25 perinatal centres in the UK, the USA and New Zealand during 1999-2002. PATIENTS: 234 infants at >=36 weeks' gestation with moderate-to-severe HIE enrolled in the CoolCap Study. 214 (91%) infants had documented plasma glucose and follow-up outcome data. INTERVENTION: Infants were randomised to head cooling for 72 h starting within 6 h of birth, or standard care. Plasma glucose levels were measured at predetermined time intervals after randomisation. MAIN OUTCOME MEASURE: The unfavourable primary outcome of the study was death and/or severe neurodevelopmental disability at 18 months. Hypoglycaemia (<=40 mg/dL, <=2.2 mmol/L) and hyperglycaemia (>150 mg/dL, >8.3 mmol/L) during the first 12 h after randomisation were investigated for univariable and multivariable associations with unfavourable primary outcome. RESULTS: 121 (57%) infants had abnormal plasma glucose values within 12 h of randomisation. Unfavourable outcome was observed in 126 (60%) infants and was more common among subjects with hypoglycaemia (81%, p=0.004), hyperglycaemia (67%, p=0.01) and any glucose derangement within the first 12 h (67%, p=0.002) compared with normoglycaemic infants (48%) in univariable analysis. These associations remained significant after adjusting for birth weight, Apgar score, pH, Sarnat stage and hypothermia therapy. CONCLUSIONS: Both hypoglycaemia and hyperglycaemia in infants with moderate-to-severe HIE were independently associated with unfavourable outcome. Future studies are needed to investigate the prognostic significance of these associations and their role as biomarkers of brain injury. TRIAL REGISTRATION NUMBER: (ClinicalTrials.gov NCT00383305). PMID- 26283671 TI - Clonal transmission of a colistin-resistant Escherichia coli from a domesticated pig to a human in Laos. PMID- 26283672 TI - Do pneumonia readmissions flagged as potentially preventable by the 3M PPR software have more process of care problems? A cross-sectional observational study. AB - BACKGROUND: In the USA, administrative data-based readmission rates such as the Centers for Medicare and Medicaid Services' all-cause readmission measures are used for public reporting and hospital payment penalties. To improve this measure and identify better quality improvement targets, 3M developed the Potentially Preventable Readmissions (PPRs) measure. It matches clinically related index admission and readmission diagnoses that may indicate readmissions resulting from admission- or post-discharge-related quality problems. OBJECTIVE: To examine whether PPR software-flagged pneumonia readmissions are associated with poorer quality of care. METHODS: Using a retrospective observational study design and Veterans Health Administration (VA) data, we identified pneumonia discharges associated with 30-day readmissions, and then flagged cases as PPR-yes or PPR-no using the PPR software. To assess quality of care, we abstracted electronic medical records of 100 random readmissions using a tool containing explicit care processes organised into admission work-up, in-hospital evaluation/treatment, discharge readiness and post-discharge period. We derived quality scores, scaled to a maximum of 25 per section (maximum total score=100) and compared cases by total and section-specific mean scores using t tests and effect size (ES) to characterise the clinical significance of findings. RESULTS: Our abstraction sample was selected from 11,278 pneumonia readmissions (readmission rate=16.5%) during 1 October 2005-30 September 2010; 77% were flagged as PPR-yes. Contrary to expectations, total and section mean quality scores were slightly higher, although non-significantly, among PPR-yes (N=77) versus PPR-no (N=23) cases (respective total scores, 71.2+/-8.7 vs 65.8+/-11.5, p=0.14); differences demonstrated ES >0.30 overall and for admission work-up and post-discharge period sections. CONCLUSIONS: Among VA pneumonia readmissions, PPR categorisation did not produce the expected quality of care findings. Either PPR-yes cases are not more preventable, or preventability assessment requires other data collection methods to capture poorly documented processes (eg, direct observation). PMID- 26283673 TI - The preclinical phase of the pathological process underlying sporadic Alzheimer's disease. AB - Abnormal tau lesions (non-argyrophilic pretangle material, argyrophilic neuropil threads, neurofibrillary tangles) in select types of neurons are crucial for the pathogenesis of sporadic Alzheimer's disease. Ongoing formation of these tau lesions persists into end-stage Alzheimer's disease and is not subject to remission. The early pretangle disease phase is a focus of increasing interest because only abnormal forms of the microtubule-associated protein tau are involved at that point and, in contrast to late-stage disease when amyloid-beta deposition is present, this phase is temporally closer to the prevailing conditions that induce the pathological process underlying Alzheimer's disease. Extracellular and aggregated amyloid-beta may only be produced under pathological conditions by nerve cells that contain abnormal tau. One potential trigger for tau protein hyperphosphorylation and conformational change in Alzheimer's disease may be the presence of a non-endogenous pathogen. Subsequently, a predictable regional distribution pattern of the tau lesions develops in phylogenetically late-appearing and ontogenetically late-maturing neurons that are connected via their axons. It is hoped that hypotheses drawn from these considerations, as well as from recent tau dissemination models, from studies of variant tau conformers, and from tau imaging will encourage the development of new preventative and disease-modifying strategies. PMID- 26283674 TI - Phosphorylation of Ribosomal Protein S6 Mediates Mammalian Target of Rapamycin Complex 1-Induced Parathyroid Cell Proliferation in Secondary Hyperparathyroidism. AB - Secondary hyperparathyroidism is characterized by increased serum parathyroid hormone (PTH) level and parathyroid cell proliferation. However, the molecular pathways mediating the increased parathyroid cell proliferation remain undefined. Here, we found that the mTOR pathway was activated in the parathyroid of rats with secondary hyperparathyroidism induced by either chronic hypocalcemia or uremia, which was measured by increased phosphorylation of ribosomal protein S6 (rpS6), a downstream target of the mTOR pathway. This activation correlated with increased parathyroid cell proliferation. Inhibition of mTOR complex 1 by rapamycin decreased or prevented parathyroid cell proliferation in secondary hyperparathyroidism rats and in vitro in uremic rat parathyroid glands in organ culture. Knockin rpS6(p-/-) mice, in which rpS6 cannot be phosphorylated because of substitution of all five phosphorylatable serines with alanines, had impaired PTH secretion after experimental uremia- or folic acid-induced AKI. Uremic rpS6(p /-) mice had no increase in parathyroid cell proliferation compared with a marked increase in uremic wild-type mice. These results underscore the importance of mTOR activation and rpS6 phosphorylation for the pathogenesis of secondary hyperparathyroidism and indicate that mTORC1 is a significant regulator of parathyroid cell proliferation through rpS6. PMID- 26283675 TI - High-Throughput Genetic Testing for Thrombotic Microangiopathies and C3 Glomerulopathies. AB - The thrombotic microangiopathies (TMAs) and C3 glomerulopathies (C3Gs) include a spectrum of rare diseases such as atypical hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, C3GN, and dense deposit disease, which share phenotypic similarities and underlying genetic commonalities. Variants in several genes contribute to the pathogenesis of these diseases, and identification of these variants may inform the diagnosis and treatment of affected patients. We have developed and validated a comprehensive genetic panel that screens all exons of all genes implicated in TMA and C3G. The closely integrated pipeline implemented includes targeted genomic enrichment, massively parallel sequencing, bioinformatic analysis, and a multidisciplinary conference to analyze identified variants in the context of each patient's specific phenotype. Herein, we present our 1-year experience with this panel, during which time we studied 193 patients. We identified 17 novel and 74 rare variants, which we classified as pathogenic (11), likely pathogenic (12), and of uncertain significance (68). Compared with controls, patients with C3G had a higher frequency of rare and novel variants in C3 convertase (C3 and CFB) and complement regulator (CFH, CFI, CFHR5, and CD46) genes (P<0.05). In contrast, patients with TMA had an increase in rare and novel variants only in complement regulator genes (P<0.01), a distinction consistent with differing sites of complement dysregulation in these two diseases. In summary, we were able to provide a positive genetic diagnosis in 43% and 41% of patients carrying the clinical diagnosis of C3G and TMA, respectively. PMID- 26283676 TI - Drug-target interaction prediction: databases, web servers and computational models. AB - Identification of drug-target interactions is an important process in drug discovery. Although high-throughput screening and other biological assays are becoming available, experimental methods for drug-target interaction identification remain to be extremely costly, time-consuming and challenging even nowadays. Therefore, various computational models have been developed to predict potential drug-target associations on a large scale. In this review, databases and web servers involved in drug-target identification and drug discovery are summarized. In addition, we mainly introduced some state-of-the-art computational models for drug-target interactions prediction, including network-based method, machine learning-based method and so on. Specially, for the machine learning based method, much attention was paid to supervised and semi-supervised models, which have essential difference in the adoption of negative samples. Although significant improvements for drug-target interaction prediction have been obtained by many effective computational models, both network-based and machine learning-based methods have their disadvantages, respectively. Furthermore, we discuss the future directions of the network-based drug discovery and network approach for personalized drug discovery based on personalized medicine, genome sequencing, tumor clone-based network and cancer hallmark-based network. Finally, we discussed the new evaluation validation framework and the formulation of drug target interactions prediction problem by more realistic regression formulation based on quantitative bioactivity data. PMID- 26283677 TI - The identification and characterization of novel transcripts from RNA-seq data. AB - Owing greatly to the advancement of next-generation sequencing (NGS), the amount of NGS data is increasing rapidly. Although there are many NGS applications, one of the most commonly used techniques 'RNA sequencing (RNA-seq)' is rapidly replacing microarray-based techniques in laboratories around the world. As more and more of such techniques are standardized, allowing technicians to perform these experiments with minimal hands-on time and reduced experimental/operator dependent biases, the bottleneck of such techniques is clearly visible; that is, data analysis. Further complicating the matter, increasing evidence suggests most of the genome is transcribed into RNA; however, the majority of these RNAs are not translated into proteins. These RNAs that do not become proteins are called 'noncoding RNAs (ncRNAs)'. Although some time has passed since the discovery of ncRNAs, their annotations remain poor, making analysis of RNA-seq data challenging. Here, we examine the current limitations of RNA-seq analysis using case studies focused on the detection of novel transcripts and examination of their characteristics. Finally, we validate the presence of novel transcripts using biological experiments, showing novel transcripts can be accurately identified when a series of filters is applied. In conclusion, novel transcripts that are identified from RNA-seq must be examined carefully before proceeding to biological experiments. PMID- 26283678 TI - Aldosterone effects on glomerular structure and function. AB - OBJECTIVE: Experimental evidence suggests that aldosterone directly contributes to organ damage by promoting cell growth, fibrosis, and inflammation. Based on these premises, this work aimed to assess the glomerular effects of aldosterone, alone and in combination with salt. METHODS: After undergoing uninephrectomy, 75 rats were allocated to five groups: control, salt diet, aldosterone, aldosterone + salt diet, aldosterone + salt diet and eplerenone, and they were all studied for four weeks. We focused on glomerular structural, functional, and molecular changes, including slit diaphragm components, local renin-angiotensin system activation, as well as pro-oxidative and profibrotic changes. RESULTS: Aldosterone significantly increased systolic blood pressure, led to glomerular hypertrophy, mesangial expansion, and it significantly increased the glomerular permeability to albumin and the albumin excretion rate, indicating the presence of glomerular damage. These effects were worsened by adding salt to aldosterone, while they were reduced by eplerenone. Aldosterone-induced glomerular damage was associated with glomerular angiotensin-converting enzyme (ACE) 2 downregulation, with ACE/ACE2 ratio increase, ANP decrease, as well as with glomerular pro oxidative and profibrotic changes. CONCLUSIONS: Aldosterone damages not only the structure but also the function of the glomerulus. ACE/ACE2 upregulation, ACE2 and ANP downregulation, and pro-oxidative and profibrotic changes are possible mechanisms accounting for aldosterone-induced glomerular injury. PMID- 26283679 TI - Correlation between renin-angiotensin system gene polymorphisms and essential hypertension in the Chinese Yi ethnic group. AB - INTRODUCTION: The renin-angiotensin system (RAS) has been considered to play an important role in the regulation of blood pressure. This study aimed to investigate the correlation between RAS gene polymorphisms and essential hypertension (EH) in the Chinese Yi ethnic group. MATERIALS AND METHODS: A total of 244 EH subjects and 185 normotensive individuals from the Chinese Yi ethnic group were genotyped for AGT M235T (rs699), AT1R A1166C (rs5186), ACE I/D (rs4340) and ACE G2350A (rs4343) polymorphisms by the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. RESULTS: Significant differences in the allele and genotype frequency of ACE G2350A were observed between the EH cases and controls (p=0.001, 0.002). After being grouped by gender, significant differences in the allele and genotype frequency of ACE G2350A and AT1R A1166C were observed between females of the EH cases and controls (ACE G2350A: p=0.000, 0.002; AT1R A1166C: p=0.008, 0.011). After excluding the influence of multifactorial interactions, the ACE G2350A polymorphism is significantly associated with the pathogenesis of EH in the Chinese Yi ethnic group (odds ratio (OR)=1.656, 95% confidence interval (CI) 1.807-2.524, p=0.019). CONCLUSIONS: The RAS-related ACE G2350A polymorphism is associated with the pathogenesis of EH in the Chinese Yi ethnic group. PMID- 26283680 TI - Delay to diagnosis in axial spondyloarthritis: are we improving in the UK? PMID- 26283681 TI - Key Stakeholders' Perceptions of Motivators for Research Participation Among Individuals Who Are Incarcerated. AB - Understanding motivations of research participants is crucial for developing ethical research protocols, especially for research with vulnerable populations. Through interviews with 92 institutional review board members, prison administrators, research ethicists, and researchers, we explored key stakeholders' perceptions of what motivates incarcerated individuals to participate in research. Primary motivators identified were a desire to contribute to society, gaining knowledge and health care, acquiring incentives, and obtaining social support. The potential for undue influence or coercion were also identified as motivators. These results highlight the need for careful analysis of what motivates incarcerated individuals to participate in research as part of developing or reviewing ethically permissible and responsible research protocols. Future research should expand this line of inquiry to directly include perspectives of incarcerated individuals. PMID- 26283683 TI - Blinatumomab for the Treatment of Philadelphia Chromosome-Negative, Precursor B cell Acute Lymphoblastic Leukemia. AB - Blinatumomab is a CD19/CD3 bispescific antibody designed to redirect T cells toward malignant B cells and induce their lysis. It recently gained accelerated approval by the FDA for the treatment of relapsed or refractory Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (RR-ALL). In the phase II trial that served as the basis for approval, blinatumomab demonstrated significant single-agent activity and induced remission [complete remission (CR) and CR with incomplete recovery of peripheral blood counts (CRh)] in 43% of 189 adult patients with RR-ALL; the majority of responders (82%) also attained negative minimal residual disease (MRD(-)) status that did not generally translate into long-term remissions in most cases. Additional studies show that blinatumomab can induce high response rates associated with lasting remissions in patients in first remission treated for MRD positivity, suggesting a role for blinatumomab in the upfront, MRD-positive setting. Blinatumomab infusion follows a predictable immunopharmacologic profile, including early cytokine release that can be associated with a clinical syndrome, T-cell expansion, and B-cell depletion. Neurologic toxicities represent a unique toxicity that shares similarities with adverse effects of other T-cell engaging therapies. Further studies are needed to clarify the optimal disease setting and timing for blinatumomab therapy. Additional insights into the pathogenesis, risk factors, and prevention of neurologic toxicities as well as a better understanding of the clinical consequences and biologic pathways that are associated with drug resistance are needed. PMID- 26283682 TI - Interactions between Ibrutinib and Anti-CD20 Antibodies: Competing Effects on the Outcome of Combination Therapy. AB - PURPOSE: Clinical trials of ibrutinib combined with anti-CD20 monoclonal antibodies (mAb) for chronic lymphocytic leukemia (CLL) report encouraging results. Paradoxically, in preclinical studies, in vitro ibrutinib was reported to decrease CD20 expression and inhibit cellular effector mechanisms. We therefore set out to investigate effects of in vivo ibrutinib treatment that could explain this paradox. EXPERIMENTAL DESIGN: Patients received single-agent ibrutinib (420 mg daily) on an investigator-initiated phase II trial. Serial blood samples were collected pretreatment and during treatment for ex vivo functional assays to examine the effects on CLL cell susceptibility to anti-CD20 mAbs. RESULTS: We demonstrate that CD20 expression on ibrutinib was rapidly and persistently downregulated (median reduction 74%, day 28, P < 0.001) compared with baseline. Concomitantly, CD20 mRNA was decreased concurrent with reduced NF kappaB signaling. An NF-kappaB binding site in the promoter of MS4A1 (encoding CD20) and downregulation of CD20 by NF-kappaB inhibitors support a direct transcriptional effect. Ex vivo, tumor cells from patients on ibrutinib were less susceptible to anti-CD20 mAb-mediated complement-dependent cytotoxicity than pretreatment cells (median reduction 75%, P < 0.001); however, opsonization by the complement protein C3d, which targets cells for phagocytosis, was relatively maintained. Expression of decay-accelerating factor (CD55) decreased on ibrutinib, providing a likely mechanism for the preserved C3d opsonization. In addition, ibrutinib significantly inhibited trogocytosis, a major contributor to antigen loss and tumor escape during mAb therapy. CONCLUSIONS: Our data indicate that ibrutinib promotes both positive and negative interactions with anti-CD20 mAbs, suggesting that successfully harnessing maximal antitumor effects of such combinations requires further investigation. PMID- 26283685 TI - The cognitive profile of ALS: a systematic review and meta-analysis update. AB - Cognitive impairment is present in approximately 30% of patients with amyotrophic lateral sclerosis (ALS) and, especially when severe, has a negative impact on survival and caregiver burden. Our 2010 meta-analysis of the cognitive profile of ALS showed impairment of fluency, executive function, language and memory. However, the limited number of studies resulted in large confidence intervals. To obtain a more valid assessment, we updated the meta-analysis and included methodological improvements (controlled data extraction, risk of bias analysis and effect size calculation of individual neuropsychological tests). Embase, Medline and PsycInfo were searched for neuropsychological studies of non-demented patients with ALS and age-matched and education-matched healthy controls. Neuropsychological tests were categorised in 13 cognitive domains and effect sizes (Hedges' g) were calculated for each domain and for individual tests administered in >=5 studies. Subgroup analyses were performed to assess the influence of clinical and demographic variables. Forty-four studies were included comprising 1287 patients and 1130 healthy controls. All cognitive domains, except visuoperceptive functions, showed significant effect sizes compared to controls. Cognitive domains without bias due to motor impairment showed medium effect sizes (95% CI): fluency (0.56 (0.43 to 0.70)), language (0.56 (0.40 to 0.72)), social cognition (0.55 (0.34 to 0.76)), or small effect sizes: delayed verbal memory 0.47 (0.27 to 0.68)) and executive functions (0.41 (0.27 to 0.55)). Individual neuropsychological tests showed diverging effect sizes, which could be explained by bias due to motor impairment. Subgroup analyses showed no influence of bulbar disease onset and depression and anxiety on the cognitive outcomes. The cognitive profile of ALS consists of deficits in fluency, language, social cognition, executive functions and verbal memory. Social cognition is a new cognitive domain with a relatively large effect size, highlighting the overlap between ALS and frontotemporal dementia. The diverging effect sizes for individual neuropsychological tests show the importance of correction for motor impairment in patients with ALS. These findings have implications for bedside testing, the design of cognitive screening measures and full neuropsychological examinations. PMID- 26283684 TI - EphA2 Expression Is a Key Driver of Migration and Invasion and a Poor Prognostic Marker in Colorectal Cancer. AB - PURPOSE: EphA2, a member of the Eph receptor tyrosine kinases family, is an important regulator of tumor initiation, neovascularization, and metastasis in a wide range of epithelial and mesenchymal cancers; however, its role in colorectal cancer recurrence and progression is unclear. EXPERIMENTAL DESIGN: EphA2 expression was determined by immunohistochemistry in stage II/III colorectal tumors (N = 338), and findings correlated with clinical outcome. The correlation between EphA2 expression and stem cell markers CD44 and Lgr5 was examined. The role of EphA2 in migration/invasion was assessed using a panel of KRAS wild-type (WT) and mutant (MT) parental and invasive colorectal cancer cell line models. RESULTS: Colorectal tumors displayed significantly higher expression levels of EphA2 compared with matched normal tissue, which positively correlated with high CD44 and Lgr5 expression levels. Moreover, high EphA2 mRNA and protein expression were found to be associated with poor overall survival in stage II/III colorectal cancer tissues, in both univariate and multivariate analyses. Preclinically, we found that EphA2 was highly expressed in KRASMT colorectal cancer cells and that EphA2 levels are regulated by the KRAS-driven MAPK and RalGDS-RalA pathways. Moreover, EphA2 levels were elevated in several invasive daughter cell lines, and downregulation of EphA2 using RNAi or recombinant EFNA1 suppressed migration and invasion of KRASMT colorectal cancer cells. CONCLUSIONS: These data show that EpHA2 is a poor prognostic marker in stage II/III colorectal cancer, which may be due to its ability to promote cell migration and invasion, providing support for the further investigation of EphA2 as a novel prognostic biomarker and therapeutic target. PMID- 26283686 TI - Loss of recent memory after bilateral hippocampal lesions: memory and memories looking back and looking forward. PMID- 26283687 TI - NF1 Mutations Prevalent but Not Clinically Relevant. AB - Whole-exome sequencing of 213 tumor samples shows that NF1 is mutated in 13.1% of melanomas. The gene is usually mutated in tumors that don't carry mutations in BRAF or NRAS, and it may be a cancer driver. However, loss of the gene didn't predict whether RAS activity increased or whether cell lines responded to inhibitors of the MAP kinase pathway, which RAS activates. PMID- 26283690 TI - Fully automated ultrasensitive digital immunoassay for cardiac troponin I based on single molecule array technology. AB - BACKGROUND: The association between increases in cardiac troponin and adverse cardiac outcomes is well established. There is a growing interest in exploring routine cardiac troponin monitoring as a potential early indicator of adverse heart health trends. Prognostic use of cardiac troponin measurements requires an assay with very high sensitivity and outstanding analytical performance. We report development and preliminary validation of an investigational assay meeting these requirements and demonstrate its applicability to cohorts of healthy individuals and patients with heart failure. METHODS: On the basis of single molecule array technology, we developed a 45-min immunoassay for cardiac troponin I (cTnI) for use on a novel, fully automated digital analyzer. We characterized its analytical performance and measured cTnI in healthy individuals and heart failure patients in a preliminary study of assay analytical efficacy. RESULTS: The assay exhibited a limit of detection of 0.01 ng/L, a limit of quantification of 0.08 ng/L, and a total CV of 10% at 2.0 ng/L. cTnI concentrations were well above the assay limit of detection for all samples tested, including samples from healthy individuals. cTnI was significantly higher in heart failure patients, and exhibited increasing median and interquartile concentrations with increasing New York Heart Association classification of heart failure severity. CONCLUSIONS: The robust 2-log increase in sensitivity relative to contemporary high-sensitivity cardiac troponin immunoassays, combined with full automation, make this assay suitable for exploring cTnI concentrations in cohorts of healthy individuals and for the potential prognostic application of serial cardiac troponin measurements in both apparently healthy and diseased individuals. PMID- 26283691 TI - Cannabis-impaired driving: a public health and safety concern. PMID- 26283689 TI - Universal and domain-specific sequences in 23S-28S ribosomal RNA identified by computational phylogenetics. AB - Comparative analysis of ribosomal RNA (rRNA) sequences has elucidated phylogenetic relationships. However, this powerful approach has not been fully exploited to address ribosome function. Here we identify stretches of evolutionarily conserved sequences, which correspond with regions of high functional importance. For this, we developed a structurally aligned database, FLORA (full-length organismal rRNA alignment) to identify highly conserved nucleotide elements (CNEs) in 23S-28S rRNA from each phylogenetic domain (Eukarya, Bacteria, and Archaea). Universal CNEs (uCNEs) are conserved in sequence and structural position in all three domains. Those in regions known to be essential for translation validate our approach. Importantly, some uCNEs reside in areas of unknown function, thus identifying novel sequences of likely great importance. In contrast to uCNEs, domain-specific CNEs (dsCNEs) are conserved in just one phylogenetic domain. This is the first report of conserved sequence elements in rRNA that are domain-specific; they are largely a eukaryotic phenomenon. The locations of the eukaryotic dsCNEs within the structure of the ribosome suggest they may function in nascent polypeptide transit through the ribosome tunnel and in tRNA exit from the ribosome. Our findings provide insights and a resource for ribosome function studies. PMID- 26283688 TI - piRNAs derived from ancient viral processed pseudogenes as transgenerational sequence-specific immune memory in mammals. AB - Endogenous bornavirus-like nucleoprotein elements (EBLNs) are sequences within vertebrate genomes derived from reverse transcription and integration of ancient bornaviral nucleoprotein mRNA via the host retrotransposon machinery. While species with EBLNs appear relatively resistant to bornaviral disease, the nature of this association is unclear. We hypothesized that EBLNs could give rise to antiviral interfering RNA in the form of PIWI-interacting RNAs (piRNAs), a class of small RNA known to silence transposons but not exogenous viruses. We found that in both rodents and primates, which acquired their EBLNs independently some 25-40 million years ago, EBLNs are present within piRNA-generating regions of the genome far more often than expected by chance alone (P = 8 * 10(-3)-6 * 10(-8)). Three of the seven human EBLNs fall within annotated piRNA clusters and two marmoset EBLNs give rise to bona fide piRNAs. In both rats and mice, at least two of the five EBLNs give rise to abundant piRNAs in the male gonad. While no EBLNs are syntenic between rodent and primate, some of the piRNA clusters containing EBLNs are; thus we deduce that EBLNs were integrated into existing piRNA clusters. All true piRNAs derived from EBLNs are antisense relative to the proposed ancient bornaviral nucleoprotein mRNA. These observations are consistent with a role for EBLN-derived piRNA-like RNAs in interfering with ancient bornaviral infection. They raise the hypothesis that retrotransposon-dependent virus-to-host gene flow could engender RNA-mediated, sequence-specific antiviral immune memory in metazoans analogous to the CRISPR/Cas system in prokaryotes. PMID- 26283694 TI - The importance of reporting suspected adverse reactions caused by new drugs. PMID- 26283693 TI - Tandem Benzophenone Amino Pyridines, Potent and Selective Inhibitors of Human Leukotriene C4 Synthase. AB - Cysteinyl leukotrienes (cys-LTs) are lipid mediators of inflammation. The enzyme catalyzing synthesis of cys-LTs, leukotriene C4 synthase (LTC4S), is considered an important drug target. Here we report the synthesis and characterization of three tandem benzophenone amino pyridines as inhibitors of LTC4S in vitro and in vivo. The inhibitors were characterized in vitro using recombinant human LTC4S, MonoMac 6 cells, and a panel of peripheral human immune cells. In vivo, the compounds were tested in the Zymosan A-induced peritonitis mouse model. The molecules, denoted TK04, TK04a, and TK05, were potent and selective inhibitors of LTC4S with IC50 values of 116, 124, and 95 nM, respectively. Molecular docking revealed binding in a hydrophobic crevice between two enzyme monomers and interaction with two catalytic residues, Arg104 and Arg31. The TK compounds potently inhibited cys-LT biosynthesis in immune cells. In coincubations of platelets and polymorphonuclear leukocytes, inhibition of LTC4S led to shunting of LTA4 toward anti-inflammatory lipoxin A4, which was significantly enhanced by simultaneous inhibition of LTA4H. Finally, we found that TK05 (6 mg?kg(-1)?body weight) reduces LTE4 levels in peritoneal lavage fluid by 88% and significantly decreases vascular permeability in vivo. Our findings indicate that the TK compounds are valuable experimental tools in eicosanoid research in vitro and in vivo. Their chemical structures may serve as leads for further inhibitor design. Novel drugs depleting cys-LT production could be beneficial for treatment of inflammatory diseases associated with overexpression of LTC4S. PMID- 26283695 TI - Reversible cerebral vasoconstriction syndrome associated with fingolimod treatment in relapsing-remitting multiple sclerosis three months after childbirth. AB - Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by acute thunderclap headache, evidence of vasoconstriction in conventional angiography or magnetic resonance angiography and reversibility of these phenomena within 12 weeks. Some triggering factors, for example drugs such as selective serotonin reuptake inhibitors, sumatriptan, tacrolimus, cyclophosphamide and cocaine, or states such as pregnancy, puerperium or migraine have been described. We describe the case of a 29-year-old woman with RCVS associated with fingolimod three months after childbirth. This case represents the first report of RCVS in fingolimod treatment. PMID- 26283692 TI - PRD125, a potent and selective inhibitor of sterol O-acyltransferase 2 markedly reduces hepatic cholesteryl ester accumulation and improves liver function in lysosomal acid lipase-deficient mice. AB - In most organs, the bulk of cholesterol is unesterified, although nearly all possess a varying capability of esterifying cholesterol through the action of either sterol O-acyltransferase (SOAT) 1 or, in the case of hepatocytes and enterocytes, SOAT2. Esterified cholesterol (EC) carried in plasma lipoproteins is hydrolyzed by lysosomal acid lipase (LAL) when they are cleared from the circulation. Loss-of-function mutations in LIPA, the gene that encodes LAL, result in Wolman disease or cholesteryl ester storage disease (CESD). Hepatomegaly and a massive increase in tissue EC levels are hallmark features of both disorders. While these conditions can be corrected with enzyme replacement therapy, the question arose as to whether pharmacological inhibition of SOAT2 might reduce tissue EC accretion in CESD. When weaned at 21 days, Lal(-/-) mice, of either gender, had a whole liver cholesterol content that was 12- to 13-fold more than that of matching Lal(+/+) littermates (23 versus 1.8 mg, respectively). In Lal(-/-) males given the selective SOAT2 inhibitor PRD125 1,11-O-o methylbenzylidene-7-O-p-cyanobenzoyl-1,7,11-trideacetylpyripyropene A in their diet (~10 mg/day per kg body weight) from 21 to 53 days, whole liver cholesterol content was 48.6 versus 153.7 mg in untreated 53-day-old Lal(-/-) mice. This difference reflected a 59% reduction in hepatic EC concentration (mg/g), combined with a 28% fall in liver mass. The treated mice also showed a 63% reduction in plasma alanine aminotransferase activity, in parallel with decisive falls in hepatic mRNA expression levels for multiple proteins that reflect macrophage presence and inflammation. These data implicate SOAT2 as a potential target in CESD management. PMID- 26283696 TI - Cerebrospinal fluid neurofilament light chain levels predict visual outcome after optic neuritis. AB - BACKGROUND: Optic neuritis is a good model for multiple sclerosis relapse, but currently no tests can accurately predict visual outcome. OBJECTIVE: The purpose of this study was to examine whether cerebrospinal fluid (CSF) biomarkers of tissue damage and remodelling (neurofilament light chain (NF-L), myelin basic protein, osteopontin and chitinase-3-like-1) predict visual outcome after optic neuritis. METHODS: We included 47 patients with optic neuritis as a first demyelinating episode. Patients underwent visual tests, optical coherence tomography (OCT), magnetic resonance imaging (MRI) and lumbar puncture. Biomarkers were measured in CSF by enzyme-linked immunosorbent assay (ELISA). Patients were followed up six months after onset and this included visual tests and OCT. Outcome measures were inter-ocular differences in low contrast visual acuity (LCVA), retinal nerve fibre layer (RNFL) and ganglion cell layer+inner plexiform layer (GC-IPL) thicknesses. RESULTS: CSF NF-L levels at onset predicted inter-ocular differences in follow-up LCVA (beta=13.8, p=0.0008), RNFL (beta=5.6, p=0.0004) and GC-IPL (beta=4.0, p=0.0008). The acute-phase GC-IPL thickness also predicted follow-up LCVA (beta=12.9, p=0.0021 for NF-L, beta=-1.1, p=0.0150 for GC-IPL). Complete/incomplete remission was determined based on LCVA from 30 healthy controls. NF-L had a positive predictive value of 91% and an area under the curve (AUC) of 0.79 for incomplete remission. CONCLUSION: CSF NF-L is a promising biomarker of visual outcome after optic neuritis. This could aid neuroprotective/regenerative medical advancements. PMID- 26283697 TI - Diagnostic Flow Cytometry and the AIDS Pandemic. AB - The onset of the AIDS pandemic in the early 1980s coincided with the convergence of technologies now collectively known as flow cytometry (FCM). Major advances in FCM led significantly toward our understanding of the pathogenicity of the disease, which in turn led to wider adoption of the technology, including using it effectively in a variety of diagnostics. CD4+ T lymphocyte population counts, along with human immunodeficiency virus (HIV) viral load, remain the gold standard in diagnosis and continue to play a major role in the monitoring of advanced retroviral therapies. Arguably, the spread of AIDS (acquired immunodeficiency syndrome), the HIV virus, and the toll of the virus on humanity have been considerably altered by the concurrent development of FCM, the details of which are presented herein. PMID- 26283698 TI - Building an Antimicrobial Stewardship Program: Cooperative Roles for Pharmacists, Infectious Diseases Specialists, and Clinical Microbiologists. AB - Efforts to optimize the use of antimicrobial agents, referred to as antimicrobial stewardship programs (ASPs), are increasingly becoming part of the clinical enterprise at big and small hospitals. Such programs aim to achieve the synergistic goals of improving patient outcomes, limiting the unintended consequences of drug resistance and superinfections, and reducing health care expenditures. This article will review the need for antimicrobial stewardship and the key components of setting up a program; then, it will describe the ASP at one medical center to underscore how attention to acceptance by the clinical staff is crucial to changing the culture of antimicrobial use. Although the details may differ for each institution, the foundation of a successful stewardship program is support from hospital leadership and the cooperative interaction among the pharmacy, infectious diseases specialists, and clinical microbiologists. PMID- 26283699 TI - aRrayLasso: a network-based approach to microarray interconversion. AB - Robust conversion between microarray platforms is needed to leverage the wide variety of microarray expression studies that have been conducted to date. Currently available conversion methods rely on manufacturer annotations, which are often incomplete, or on direct alignment of probes from different platforms, which often fail to yield acceptable genewise correlation. Here, we describe aRrayLasso, which uses the Lasso-penalized generalized linear model to model the relationships between individual probes in different probe sets. We have implemented aRrayLasso in a set of five open-source R functions that allow the user to acquire data from public sources such as Gene Expression Omnibus, train a set of Lasso models on that data and directly map one microarray platform to another. aRrayLasso significantly predicts expression levels with similar fidelity to technical replicates of the same RNA pool, demonstrating its utility in the integration of datasets from different platforms. AVAILABILITY AND IMPLEMENTATION: All functions are available, along with descriptions, at https://github.com/adam-sam-brown/aRrayLasso. CONTACT: chirag_patel@hms.harvard.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26283704 TI - Detection of tumour cells in the bloodstream of patients with uveal melanoma: influence of surgical manipulation on the dissemination of tumour cells in the bloodstream. AB - AIM: The detection of circulating tumour cells in the bloodstream before and after surgical manipulation, and the qualitative detection of potential shedding of tumour cells during surgical manipulation of patients with uveal melanoma. METHODS: 202 patients treated for a newly diagnosed uveal melanoma were included in the study. Blood samples were acquired 24 h before and 30 min after the basic surgical steps. Detection of potential circulating melanoma cells was extrapolated from the presence of tyrosinase and MelanA/Mart1 transcripts by reverse transcription PCR. RESULTS: Based on the measurement of tyrosinase transcripts, as a result of the first and second surgical manipulation there were three and zero transitions from negative to positive respectively, while there were two and one transitions from positive to negative, respectively. According to MelanA/Mart1 transcripts, there were 19 and 5 transitions from negative to positive respectively, and 15 and 2 transitions from positive to negative, respectively. No statistically significant differences were documented, concerning the presence of circulating tumour cells in the blood samples acquired before and after the first surgical manipulation or the second one. CONCLUSION: The change in the percentage of patients with detected tumour cells in their bloodstream was not statistically significant. The frequent shifts from negative to positive samples as well as from positive to negative samples comparing preoperative to postoperative samples indicates discontinuous shedding or variation due to measurements close to the threshold of detection. As a conclusion, the surgical manipulation does not seem to have a measurable contribution to the spread of melanoma cells in the bloodstream. PMID- 26283667 TI - Exploring threats to generalisability in a large international rehabilitation trial (AVERT). AB - OBJECTIVE: The purpose of this paper is to examine potential threats to generalisability of the results of a multicentre randomised controlled trial using data from A Very Early Rehabilitation Trial (AVERT). DESIGN: AVERT is a prospective, parallel group, assessor-blinded randomised clinical trial. This paper presents data assessing the generalisability of AVERT. SETTING: Acute stroke units at 44 hospitals in 8 countries. PARTICIPANTS: The first 20,000 patients screened for AVERT, of whom 1158 were recruited and randomised. MODEL: We use the Proximal Similarity Model, which considers the person, place, and setting and practice, as a framework for considering generalisability. As well as comparing the recruited patients with the target population, we also performed an exploratory analysis of the demographic, clinical, site and process factors associated with recruitment. RESULTS: The demographics and stroke characteristics of the included patients in the trial were broadly similar to population-based norms, with the exception that AVERT had a greater proportion of men. The most common reason for non-recruitment was late arrival to hospital (ie, >24 h). Overall, being older and female reduced the odds of recruitment to the trial. More women than men were excluded for most of the reasons, including refusal. The odds of exclusion due to early deterioration were particularly high for those with severe stroke (OR=10.4, p<0.001, 95% CI 9.27 to 11.65). CONCLUSIONS: A model which explores person, place, and setting and practice factors can provide important information about the external validity of a trial, and could be applied to other clinical trials. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12606000185561) and Clinicaltrials.gov (NCT01846247). PMID- 26283705 TI - Three dimensional de novo micro bone marrow and its versatile application in drug screening and regenerative medicine. AB - The finding that bone marrow hosts several types of multipotent stem cell has prompted extensive research aimed at regenerating organs and building models to elucidate the mechanisms of diseases. Conventional research depends on the use of two-dimensional (2D) bone marrow systems, which imposes several obstacles. The development of 3D bone marrow systems with appropriate molecules and materials however, is now showing promising results. In this review, we discuss the advantages of 3D bone marrow systems over 2D systems and then point out various factors that can enhance the 3D systems. The intensive research on 3D bone marrow systems has revealed multiple important clinical applications including disease modeling, drug screening, regenerative medicine, etc. We also discuss some possible future directions in the 3D bone marrow research field. PMID- 26283706 TI - Spectrin's chimeric E2/E3 enzymatic activity. AB - In this minireview, we cover the discovery of the human erythrocyte alpha spectrin E2/E3 ubiquitin conjugating/ligating enzymatic activity and the specific cysteines involved. We then discuss the consequences when this activity is partially inhibited in sickle cell disease and the possibility that the same attenuation is occurring in multiple organ dysfunction syndrome. We finish by discussing the reasons for believing that nonerythroid alpha spectrin isoforms (I and II) also have this activity and the importance of testing this hypothesis. If correct, this would suggest that the nonerythroid spectrin isoforms play a major role in protein ubiquitination in all cell types. This would open new fields in experimental biology focused on uncovering the impact that this enzymatic activity has upon protein-protein interactions, protein turnover, cellular signaling, and many other functions impacted by spectrin, including DNA repair. PMID- 26283708 TI - Use of Optimization Modeling for Selecting National Micronutrient Intervention Strategies: An Example Based on Potential Programs for Control of Vitamin A Deficiency in Cameroon. AB - Vitamin and mineral (micronutrient [MN]) deficiencies are common in lower income countries, especially among young children and women of reproductive age. These deficiencies are cause for serious concern because of their high prevalence and their associated complications, which include depressed immune function and increased risk and severity of infections, impaired neurocognitive development, and anemia, which together result in elevated mortality and reduced human productive capacity. A broad range of different intervention strategies are available to control MN deficiencies. At present, these interventions are usually implemented at a national scale through different public and private sector entities, often with little coordination. We have developed a set of models based on the estimated ability of different interventions to achieve effective coverage and the necessary financial resources required to deploy these interventions. The models provide a unified and transparent framework for considering different options using the common indicator of effective coverage. More specifically, information on nutritional benefits and costs are analyzed using an economic optimization model to identify the mix of interventions that could be delivered to specific target groups in particular geographic areas to achieve a desired level of effective coverage at lowest cost. Alternatively, these optimization models can be developed to identify the combination of interventions needed to achieve the maximum effective coverage, given specified budgetary limitations. The results of these models can be useful input into policy-making processes. To introduce this analytical approach, the set of papers in this volume addresses the problem of vitamin A deficiency among young children in Cameroon. PMID- 26283709 TI - Gait speed and readmission following hospitalisation for acute exacerbations of COPD: a prospective study. AB - BACKGROUND: Hospitalisation for acute exacerbations of COPD is associated with high risk of readmission. However, no tool has been validated to stratify patients at discharge for risk of readmission. AIM: To evaluate the ability of the 4 m gait speed (4MGS), a surrogate marker of frailty, to predict risk of future readmission in hospitalised patients with an acute exacerbation of COPD (AECOPD). METHODS: 213 patients hospitalised with an AECOPD were recruited prospectively. 4MGS was measured on day of discharge. Logistic regression models were used to assess the association between 4MGS and readmission at 90 days after discharge. RESULTS: Baseline characteristics of the cohort: 52% men; mean age 72 years; median FEV1 35%predicted. Mean (SD) 4MGS at hospital discharge was 0.61 (0.26) ms(-1). Significant increased rates of all-cause readmission at 90 days were seen across quartiles of decreasing 4MGS (Q4 fastest: 11.5%; Q3: 20.4%; Q2: 30.2%; Q1 slowest: 48.2%; p trend<0.001). Compared with Q4, those in the slowest 4MGS quartile had unadjusted ORs (95% CIs) for 90-day readmission of 7.12 (2.61 to 19.44) for the whole cohort and 11.56 (3.08 to 43.35) in those aged 65 or over. A multivariate model incorporating 4MGS, Charlson Index, hospital admission in past year, FEV1%predicted and number of exacerbations in past year in those aged 65 or over predicted 90-day readmission with a C-statistic of 0.86. CONCLUSIONS: The 4MGS, a surrogate marker of physical frailty, independently predicts the risk of readmission in older patients hospitalised for acute exacerbation of COPD. TRIAL REGISTRATION NUMBER: NCT01507415. PMID- 26283707 TI - Cell signaling pathways involved in drug-mediated fetal hemoglobin induction: Strategies to treat sickle cell disease. AB - The developmental regulation of globin gene expression has shaped research efforts to establish therapeutic modalities for individuals affected with sickle cell disease and beta-thalassemia. Fetal hemoglobin has been shown to block sickle hemoglobin S polymerization to improve symptoms of sickle cell disease; moreover, fetal hemoglobin functions to replace inadequate hemoglobin A synthesis in beta-thalassemia thus serving as an effective therapeutic target. In the perinatal period, fetal hemoglobin is synthesized at high levels followed by a decline to adult levels by one year of age. It is known that naturally occurring mutations in the gamma-globin gene promoters and distant cis-acting transcription factors produce persistent fetal hemoglobin synthesis after birth to ameliorate clinical symptoms. Major repressor proteins that silence gamma-globin during development have been targeted for gene therapy in beta-hemoglobinopathies patients. In parallel effort, several classes of pharmacological agents that induce fetal hemoglobin expression through molecular and cell signaling mechanisms have been identified. Herein, we reviewed the progress made in the discovery of signaling molecules targeted by pharmacologic agents that enhance gamma-globin expression and have the potential for future drug development to treat the beta-hemoglobinopathies. PMID- 26283711 TI - Corrigendum. PMID- 26283710 TI - beta-Blockers are associated with a reduction in COPD exacerbations. AB - BACKGROUND: While some retrospective studies have suggested that beta-blocker use in patients with COPD is associated with a reduction in the frequency of acute exacerbations and lower mortality, there is concern that their use in patients with severe COPD on home oxygen may be harmful. METHODS: Subjects with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2-4 COPD participating in a prospective follow-up of the COPDGene cohort, a multicentre observational cohort of current and former smokers were recruited. Total and severe exacerbation rates were compared between groups categorised by beta blocker use on longitudinal follow-up using negative binomial regression analyses, after adjustment for demographics, airflow obstruction, %emphysema on CT, respiratory medications, presence of coronary artery disease, congestive heart failure and coronary artery calcification, and after adjustment for propensity to prescribe beta-blockers. RESULTS: 3464 subjects were included. During a median of 2.1 years of follow-up, beta-blocker use was associated with a significantly lower rate of total (incidence risk ratio (IRR) 0.73, 95% CI 0.60 to 0.90; p=0.003) and severe exacerbations (IRR 0.67, 95% CI 0.48 to 0.93; p=0.016). In those with GOLD stage 3 and 4 and on home oxygen, use of beta blockers was again associated with a reduction in the rate of total (IRR 0.33, 95% CI 0.19 to 0.58; p<0.001) and severe exacerbations (IRR 0.35, 95% CI 0.16 to 0.76; p=0.008). Exacerbation reduction was greatest in GOLD stage B. There was no difference in all-cause mortality with beta-blocker use. CONCLUSIONS: beta Blockers are associated with a significant reduction in COPD exacerbations regardless of severity of airflow obstruction. The findings of this study should be tested in a randomised, placebo-controlled trial. TRIAL REGISTRATION NUMBER: (ClinicalTrials.gov NCT00608764). PMID- 26283712 TI - Physicochemical properties and structural characteristics of whole grain Oryza sativa L. with different treatments. AB - Physicochemical properties and structural characteristics of whole rice flours with different treatments (soaking, germination and extrusion cooking) were studied. Water solubility, water absorption, crystallinity, adsorption isotherms (BET and GAB models), and glass transition temperature of the samples were determined. Water solubility and water absorption were enhanced by extrusion cooking process (3.17-4.98 vs. 24.1-53.76 g/100 g and 2.77-3.05 vs. 4.46-7.04 ml/g, respectively), but crystallinity was decreased (30-33 vs. 4-16%). Adsorption isotherms showed that extruded samples exhibited higher equilibrium moisture content as compared with their corresponding non-extruded samples (5.0 19.2 vs. 4.0-16.1 g water/g solids). There were no changes in glass transition temperature values in the studied moisture range (3.8-16 g/100 g). These results allow the correct use of whole rice flours with different treatments in foods and also contributed to the knowledge of stabilization of the products. PMID- 26283715 TI - Growing the evidence base for medical cannabis. PMID- 26283713 TI - Quitting smoking before and after varenicline: a population study based on two representative samples of US smokers. AB - BACKGROUND: Varenicline is known to have greater efficacy than other pharmacotherapy for treating nicotine dependence and has gained popularity since its introduction in 2006. This study examines if adding varenicline to existing pharmacotherapies increased the population cessation rate. METHODS: Data are from two cross-sectional US Current Population Surveys-Tobacco Use Supplements (2003 and 2010-2011). Smokers and recent quitters 18 or older (N=34 869 in 2003, N=27 751 in 2010-2011) were asked if they had used varenicline, bupropion or nicotine replacement therapies (NRT) in their most recent quit attempt. The annual cessation rate, as well as the per cent of smokers who had quit for >=3 months, was compared between surveys. RESULTS: Varenicline use increased from 0% in 2003 to 10.9% in 2010-2011, while use of bupropion decreased from 9.1% to 3.5%, and NRT from 24.5% to 22.4%. Use of any pharmacotherapy increased by 2.4 percentage points. Varenicline users stayed on cessation aids longer and were less likely to relapse than users of other pharmacotherapies in the first 3 months of a quit attempt, after which the difference was no longer significant. The change in annual cessation rate was negligible, from 4.5% in 2003 to 4.7% in 2010-2011 (p=0.36). CONCLUSIONS: Addition of varenicline to the list of approved cessation aids has mainly led to displacement of other therapies. As a result, there was no meaningful change in population cessation rate despite a remarkable increase in varenicline use. The population impact of a new therapy is a function of more than efficacy or reach of the therapy. PMID- 26283714 TI - Posterior circulation CT angiography collaterals predict outcome of endovascular acute ischemic stroke therapy for basilar artery occlusion. AB - INTRODUCTION: The natural history of acute ischemic stroke (AIS) due to basilar artery occlusion (BAO) is poor. Endovascular reperfusion therapy (EVT) improves recanalization rates in patients with emergent large vessel intracranial occlusion. OBJECTIVE: To examine the hypothesis that good collateral patterns identified by pretreatment CT angiography (CTA) might be associated with favorable outcomes after EVT. METHODS: We conducted a retrospective chart review of patients presenting with AIS due to BAO in a tertiary care stroke center during a 4-year period. BAO was diagnosed by CTA in all cases. Admission stroke severity was documented using the National Institute of Health Stroke Scale (NIHSS) score. Pretreatment collateral score for posterior circulation was defined as follows: 0, no posterior communicating artery (PCOM); 1, unilateral PCOM; 2, bilateral PCOM. Favorable outcome was defined as modified Rankin Scale score of 0-2 at 3 months. RESULTS: A total of 21 patients with AIS due to BAO (age range 31-84 years, median admission NIHSS score: 18 points, range 2-38) underwent EVT. Eleven of 21 patients (52.4%) had bilateral PCOMs, while unilateral PCOM was seen in 3 patients (14.3%). Patients with bilateral PCOMs tended (p=0.261) to have less severe stroke at admission than those with absent/unilateral PCOM (median NIHSS score 18 vs 27 points). Neurological improvement during hospitalization (quantified by the median decrease in NIHSS score) and the rate of 3-month functional independence were greater in patients with good collaterals (16 vs 0 points (p=0.016) and 72.7% vs 0% (p=0.001)). CONCLUSIONS: The presence of bilateral PCOMs on pretreatment CTA appears to be associated with more favorable outcomes in BAO treated with EVT. PMID- 26283717 TI - The rhetoric of female sexual dysfunction: faux feminism and the FDA. PMID- 26283716 TI - Physician experience and outcomes among patients admitted to general internal medicine teaching wards. AB - BACKGROUND: Physician scores on examinations decline with time after graduation. However, whether this translates into declining quality of care is unknown. Our objective was to determine how physician experience is associated with negative outcomes for patients admitted to hospital. METHODS: We conducted a retrospective cohort study involving all patients admitted to general internal medicine wards over a 2-year period at all 7 teaching hospitals in Alberta, Canada. We used files from the Alberta College of Physicians and Surgeons to determine the number of years since medical school graduation for each patient's most responsible physician. Our primary outcome was the composite of in-hospital death, or readmission or death within 30 days postdischarge. RESULTS: We identified 10 046 patients who were cared for by 149 physicians. Patient characteristics were similar across physician experience strata, as were primary outcome rates (17.4% for patients whose care was managed by physicians in the highest quartile of experience, compared with 18.8% in those receiving care from the least experienced physicians; adjusted odds ratio [OR] 0.88, 95% confidence interval [CI] 0.72-1.06). Outcomes were similar between experience quartiles when further stratified by physician volume, most responsible diagnosis or complexity of the patient's condition. Although we found substantial variability in length of stay between individual physicians, there were no significant differences between physician experience quartiles (mean adjusted for patient covariates and accounting for intraphysician clustering: 7.90 [95% CI 7.39-8.42] d for most experienced quartile; 7.63 [95% CI 7.13-8.14] d for least experienced quartile). INTERPRETATION: For patients admitted to general internal medicine teaching wards, we saw no negative association between physician experience and outcomes commonly used as proxies for quality of inpatient care. PMID- 26283718 TI - Acute conjunctivitis and corneal foreign bodies secondary to tarantula hairs. PMID- 26283719 TI - WMA investigates its future president. PMID- 26283720 TI - Why the federal government must lead in health care. PMID- 26283722 TI - New guide helps doctors in radiation emergency. PMID- 26283721 TI - Diffuse reticulate purpura in a boy with anorexia nervosa. PMID- 26283723 TI - Online tool helps future MDs plan their careers. PMID- 26283724 TI - Aquagenic wrinkling of the palms. PMID- 26283725 TI - Food insecurity: What is the clinician's role? PMID- 26283726 TI - Whole-Body In Vivo Monitoring of Inflammatory Diseases Exploiting Human Interleukin 6-Luciferase Transgenic Mice. AB - Chronic inflammation underlies the pathological progression of various diseases, and thus many efforts have been made to quantitatively evaluate the inflammatory status of the diseases. In this study, we generated a highly sensitive inflammation-monitoring mouse system using a bacterial artificial chromosome (BAC) clone containing extended flanking sequences of the human interleukin 6 gene (hIL6) locus, in which the luciferase (Luc) reporter gene is integrated (hIL6-BAC-Luc). We successfully monitored lipopolysaccharide-induced systemic inflammation in various tissues of the hIL6-BAC-Luc mice using an in vivo bioluminescence imaging system. When two chronic inflammatory disease models, i.e., a genetic model of atopic dermatitis and a model of experimental autoimmune encephalomyelitis (EAE), were applied to the hIL6-BAC-Luc mice, luciferase bioluminescence was specifically detected in the atopic skin lesion and central nervous system, respectively. Moreover, the Luc activities correlated well with the disease severity. Nrf2 is a master transcription factor that regulates antioxidative and detoxification enzyme genes. Upon EAE induction, the Nrf2 deficient mice crossed with the hIL6-BAC-Luc mice exhibited enhanced neurological symptoms concomitantly with robust luciferase luminescence in the neuronal tissue. Thus, whole-body in vivo monitoring using the hIL6-BAC-Luc transgenic system (WIM-6 system) provides a new and powerful diagnostic tool for real-time in vivo monitoring of inflammatory status in multiple different disease models. PMID- 26283727 TI - A Synthetic Lethal Interaction between Glutathione Synthesis and Mitochondrial Reactive Oxygen Species Provides a Tumor-Specific Vulnerability Dependent on STAT3. AB - Increased production of mitochondrion-derived reactive oxygen species (ROS) is characteristic of a metabolic shift observed during malignant transformation. While the exact sources and roles of ROS in tumorigenesis remain to be defined, it has become clear that maintaining redox balance is critical for cancer cell proliferation and survival and, as such, may represent a vulnerability that can be exploited therapeutically. STAT3, a latent cytosolic transcription factor activated by diverse cytokines and growth factors, has been shown to exhibit an additional, nontranscriptional function in mitochondria, including modulation of electron transport chain activity. In particular, malignant transformation by Ras oncogenes exploits mitochondrial STAT3 functions. We used mass spectrometry-based metabolomics profiling to explore the biochemical basis for the STAT3 dependence of Ras transformation. We identified the gamma-glutamyl cycle, the production of glutathione, and the regulation of ROS as a mitochondrion-STAT3-dependent pathway in Ras-transformed cells. Experimental inhibition of key enzymes in the glutathione cycle resulted in the depletion of glutathione, accumulation of ROS, oxidative DNA damage, and cell death in an oncogenic Ras- and mitochondrial STAT3 dependent manner. These data uncover a synthetic lethal interaction involving glutathione production and mitochondrial ROS regulation in Ras-transformed cells that is governed by mitochondrial STAT3 and might be exploited therapeutically. PMID- 26283728 TI - Notch1 Autoactivation via Transcriptional Regulation of Furin, Which Sustains Notch1 Signaling by Processing Notch1-Activating Proteases ADAM10 and Membrane Type 1 Matrix Metalloproteinase. AB - Notch1 is an evolutionarily conserved transmembrane receptor involved in melanoma growth. Notch1 is first cleaved by furin in the Golgi apparatus to produce the biologically active heterodimer. Following ligand binding, Notch1 is cleaved at the cell membrane by proteases such as ADAM10 and -17 and membrane type 1 matrix metalloproteinase (MT1-MMP), the latter of which we recently identified as a novel protease involved in Notch1 processing. The final cleavage is gamma secretase dependent and releases the active Notch intracellular domain (NIC). We now demonstrate that Notch1 directly regulates furin expression. Aside from activating Notch1, furin cleaves and activates several proteases, including MT1 MMP, ADAM10, and ADAM17. By chromatin immunoprecipitation and a reporter assay, we demonstrate that Notch1 binds at position -1236 of the furin promoter and drives furin expression. The Notch1-dependent enhancement of furin expression increases the activities of MT1-MMP and ADAM10 but not that of ADAM17, as demonstrated by short hairpin RNA (shRNA) knockdown of furin, and promotes the cleavage of Notch1 itself. These data highlight a novel positive-feedback loop whereby Notch1-dependent furin expression can induce Notch1 signaling by increasing Notch1 processing and by potentiating the activity of the proteases responsible for Notch1 activation. This leads to Notch1 signal amplification, which can promote melanoma tumor growth and progression, as demonstrated by the inhibition of cell migration and invasion upon furin inhibition downstream of Notch1. Disruption of such feedback signaling might represent an avenue for the treatment of melanoma. PMID- 26283729 TI - Role of the Exocyst Complex Component Sec6/8 in Genomic Stability. AB - The exocyst is a heterooctomeric complex well appreciated for its role in the dynamic assembly of specialized membrane domains. Accumulating evidence indicates that this macromolecular machine also serves as a physical platform that coordinates regulatory cascades supporting biological systems such as host defense signaling, cell fate, and energy homeostasis. The isolation of multiple components of the DNA damage response (DDR) as exocyst-interacting proteins, together with the identification of Sec8 as a suppressor of the p53 response, suggested functional interactions between the exocyst and the DDR. We found that exocyst perturbation resulted in resistance to ionizing radiation (IR) and accelerated resolution of DNA damage. This occurred at the expense of genomic integrity, as enhanced recombination frequencies correlated with the accumulation of aberrant chromatid exchanges. Sec8 perturbation resulted in the accumulation of ATF2 and RNF20 and the promiscuous accumulation of DDR-associated chromatin marks and Rad51 repairosomes. Thus, the exocyst supports DNA repair fidelity by limiting the formation of repair chromatin in the absence of DNA damage. PMID- 26283730 TI - Different Mechanisms Confer Gradual Control and Memory at Nutrient- and Stress Regulated Genes in Yeast. AB - Cells respond to environmental stimuli by fine-tuned regulation of gene expression. Here we investigated the dose-dependent modulation of gene expression at high temporal resolution in response to nutrient and stress signals in yeast. The GAL1 activity in cell populations is modulated in a well-defined range of galactose concentrations, correlating with a dynamic change of histone remodeling and RNA polymerase II (RNAPII) association. This behavior is the result of a heterogeneous induction delay caused by decreasing inducer concentrations across the population. Chromatin remodeling appears to be the basis for the dynamic GAL1 expression, because mutants with impaired histone dynamics show severely truncated dose-response profiles. In contrast, the GRE2 promoter operates like a rapid off/on switch in response to increasing osmotic stress, with almost constant expression rates and exclusively temporal regulation of histone remodeling and RNAPII occupancy. The Gal3 inducer and the Hog1 mitogen-activated protein (MAP) kinase seem to determine the different dose-response strategies at the two promoters. Accordingly, GAL1 becomes highly sensitive and dose independent if previously stimulated because of residual Gal3 levels, whereas GRE2 expression diminishes upon repeated stimulation due to acquired stress resistance. Our analysis reveals important differences in the way dynamic signals create dose-sensitive gene expression outputs. PMID- 26283731 TI - Loss of ADAM17-Mediated Tumor Necrosis Factor Alpha Signaling in Intestinal Cells Attenuates Mucosal Atrophy in a Mouse Model of Parenteral Nutrition. AB - Total parenteral nutrition (TPN) is commonly used clinically to sustain patients; however, TPN is associated with profound mucosal atrophy, which may adversely affect clinical outcomes. Using a mouse TPN model, removing enteral nutrition leads to decreased crypt proliferation, increased intestinal epithelial cell (IEC) apoptosis and increased mucosal tumor necrosis factor alpha (TNF-alpha) expression that ultimately produces mucosal atrophy. Upregulation of TNF-alpha signaling plays a central role in mediating TPN-induced mucosal atrophy without intact epidermal growth factor receptor (EGFR) signaling. Currently, the mechanism and the tissue-specific contributions of TNF-alpha signaling to TPN induced mucosal atrophy remain unclear. ADAM17 is an ectodomain sheddase that can modulate the signaling activity of several cytokine/growth factor receptor families, including the TNF-alpha/TNF receptor and ErbB ligand/EGFR pathways. Using TPN-treated IEC-specific ADAM17-deficient mice, the present study demonstrates that a loss of soluble TNF-alpha signaling from IECs attenuates TPN induced mucosal atrophy. Importantly, this response remains dependent on the maintenance of functional EGFR signaling in IECs. TNF-alpha blockade in wild-type mice receiving TPN confirmed that soluble TNF-alpha signaling is responsible for downregulation of EGFR signaling in IECs. These results demonstrate that ADAM17 mediated TNF-alpha signaling from IECs has a significant role in the development of the proinflammatory state and mucosal atrophy observed in TPN-treated mice. PMID- 26283732 TI - Cdc14A and Cdc14B Redundantly Regulate DNA Double-Strand Break Repair. AB - Cdc14 is a phosphatase that controls mitotic exit and cytokinesis in budding yeast. In mammals, the two Cdc14 homologues, Cdc14A and Cdc14B, have been proposed to regulate DNA damage repair, whereas the mitotic exit and cytokinesis rely on another phosphatase, PP2A-B55alpha. It is unclear if the two Cdc14s work redundantly in DNA repair and which repair pathways they participate in. More importantly, their target(s) in DNA repair remains elusive. Here we report that Cdc14B knockout (Cdc14B(-/-)) mouse embryonic fibroblasts (MEFs) showed defects in repairing ionizing radiation (IR)-induced DNA double-strand breaks (DSBs), which occurred only at late passages when Cdc14A levels were low. This repair defect could occur at early passages if Cdc14A levels were also compromised. These results indicate redundancy between Cdc14B and Cdc14A in DSB repair. Further, we found that Cdc14B deficiency impaired both homologous recombination (HR) and nonhomologous end joining (NHEJ), the two major DSB repair pathways. We also provide evidence that Cdh1 is a downstream target of Cdc14B in DSB repair. PMID- 26283733 TI - Neuroinflammation-Induced Interactions between Protease-Activated Receptor 1 and Proprotein Convertases in HIV-Associated Neurocognitive Disorder. AB - The proprotein convertases (PCs) furin, PC5, PACE4, and PC7 cleave secretory proteins after basic residues, including the HIV envelope glycoprotein (gp160) and Vpr. We evaluated the abundance of PC mRNAs in postmortem brains of individuals exhibiting HIV-associated neurocognitive disorder (HAND), likely driven by neuroinflammation and neurotoxic HIV proteins (e.g., envelope and Vpr). Concomitant with increased inflammation-related gene expression (interleukin 1beta [IL-1beta]), the mRNA levels of the above PCs are significantly increased, together with those of the proteinase-activated receptor 1 (PAR1), an inflammation-associated receptor that is cleaved by thrombin at ProArg41? (where the down arrow indicates the cleavage location), and potentially by PCs at Arg41XXXXArg46?. The latter motif in PAR1, but not its R46A mutant, drives its interactions with PCs. Indeed, PAR1 upregulation leads to the inhibition of membrane-bound furin, PC5B, and PC7 and inhibits gp160 processing and HIV infectivity. Additionally, a proximity ligation assay revealed that furin and PC7 interact with PAR1. Reciprocally, increased furin expression reduces the plasma membrane abundance of PAR1 by trapping it in the trans-Golgi network. Furthermore, soluble PC5A/PACE4 can target/disarm cell surface PAR1 through cleavage at Arg46?. PACE4/PC5A decreased calcium mobilization induced by thrombin stimulation. Our data reveal a new PC-PAR1-interaction pathway, which offsets the effects of HIV-induced neuroinflammation, viral infection, and potentially the development of HAND. PMID- 26283734 TI - miR-92a Corrects CD34+ Cell Dysfunction in Diabetes by Modulating Core Circadian Genes Involved in Progenitor Differentiation. AB - Autologous CD34(+) cells are widely used for vascular repair; however, in individuals with diabetes and microvascular disease these cells are dysfunctional. In this study, we examine expression of the clock genes Clock, Bmal, Per1, Per2, Cry1, and Cry2 in CD34(+) cells of diabetic and nondiabetic origin and determine the small encoding RNA (miRNA) profile of these cells. The degree of diabetic retinopathy (DR) was assessed. As CD34(+) cells acquired mature endothelial markers, they exhibit robust oscillations of clock genes. siRNA treatment of CD34(+) cells revealed Per2 as the only clock gene necessary to maintain the undifferentiated state of CD34(+) cells. Twenty-five miRNAs targeting clock genes were identified. Three of the miRNAs (miR-18b, miR-16, and miR-34c) were found only in diabetic progenitors. The expression of the Per2 regulatory miRNA, miR-92a, was markedly reduced in CD34(+) cells from individuals with DR compared with control subjects and patients with diabetes with no DR. Restoration of miR-92a levels in CD34(+) cells from patients with diabetes with DR reduced the inflammatory phenotype of these cells and the diabetes-induced propensity toward myeloid differentiation. Our studies suggest that restoring levels of miR-92a could enhance the usefulness of CD34(+) cells in autologous cell therapy. PMID- 26283736 TI - Liraglutide Reduces CNS Activation in Response to Visual Food Cues Only After Short-term Treatment in Patients With Type 2 Diabetes. AB - OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are associated with reduced appetite and body weight. We investigated whether these effects could be mediated by the central nervous system (CNS). RESEARCH DESIGN AND METHODS: We performed a randomized crossover study in obese patients with type 2 diabetes (n = 20, mean age 59.3 +/- 4.1 years, mean BMI 32 +/- 4.7 kg/m(2)), consisting of two periods of 12-week treatment with either liraglutide 1.8 mg or insulin glargine. Using functional MRI, we determined the effects of treatment on CNS responses to viewing food pictures in the fasted condition and 30 min after meal intake. RESULTS: After 12 weeks, the decrease in HbA1c was larger with liraglutide versus insulin glargine (Delta-0.7% vs. -0.2%, P < 0.001). Body weight decreased during liraglutide versus insulin glargine (Delta-3.3 kg vs. 0.8 kg, P < 0.001). After 10 days, patients treated with liraglutide, compared with insulin glargine, showed decreased responses to food pictures in insula and putamen (P <= 0.02). In addition, liraglutide enhanced the satiating effect of meal intake on responses in putamen and amygdala (P <= 0.05). Differences between liraglutide and insulin glargine were not observed after 12 weeks. CONCLUSIONS: Compared with insulin, liraglutide decreased CNS activation significantly only after short-term treatment, suggesting that these effects of GLP-1RA on the CNS may contribute to the induction of weight loss, but not necessarily to its maintenance, in view of the absence of an effect of liraglutide on CNS activation in response to food pictures after longer-term treatment. PMID- 26283735 TI - The DeltaF508 Mutation in the Cystic Fibrosis Transmembrane Conductance Regulator Is Associated With Progressive Insulin Resistance and Decreased Functional beta Cell Mass in Mice. AB - Cystic fibrosis (CF) is the result of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). CF-related diabetes affects 50% of adult CF patients. How CFTR deficiency predisposes to diabetes is unknown. Herein, we examined the impact of the most frequent cftr mutation in humans, deletion of phenylalanine at position 508 (DeltaF508), on glucose homeostasis in mice. We compared DeltaF508 mutant mice with wild-type (WT) littermates. Twelve week-old male DeltaF508 mutants had lower body weight, improved oral glucose tolerance, and a trend toward higher insulin tolerance. Glucose-induced insulin secretion was slightly diminished in DeltaF508 mutant islets, due to reduced insulin content, but DeltaF508 mutant islets were not more sensitive to proinflammatory cytokines than WT islets. Hyperglycemic clamps confirmed an increase in insulin sensitivity with normal beta-cell function in 12- and 18-week old DeltaF508 mutants. In contrast, 24-week-old DeltaF508 mutants exhibited insulin resistance and reduced beta-cell function. beta-Cell mass was unaffected at 11 weeks of age but was significantly lower in DeltaF508 mutants versus controls at 24 weeks. This was not associated with gross pancreatic pathology. We conclude that the DeltaF508 CFTR mutation does not lead to an intrinsic beta-cell secretory defect but is associated with insulin resistance and a beta-cell mass deficit in aging mutants. PMID- 26283737 TI - Rates of diabetic ketoacidosis: international comparison with 49,859 pediatric patients with type 1 diabetes from England, Wales, the U.S., Austria, and Germany. AB - OBJECTIVE: Diabetic ketoacidosis (DKA) in children and adolescents with established type 1 diabetes is a major problem with considerable morbidity, mortality, and associated costs to patients, families, and health care systems. We analyzed data from three multinational type 1 diabetes registries/audits with similarly advanced, yet differing, health care systems with an aim to identify factors associated with DKA admissions. RESEARCH DESIGN AND METHODS: Data from 49,859 individuals <18 years with type 1 diabetes duration >=1 year from the Prospective Diabetes Follow-up Registry (DPV) initiative (n = 22,397, Austria and Germany), the National Paediatric Diabetes Audit (NPDA; n = 16,314, England and Wales), and the T1D Exchange (T1DX; n = 11,148, U.S.) were included. DKA was defined as >=1 hospitalization for hyperglycemia with a pH <7.3 during the prior year. Data were analyzed using multivariable logistic regression models. RESULTS: The frequency of DKA was 5.0% in DPV, 6.4% in NPDA, and 7.1% in T1DX, with differences persisting after demographic adjustment (P < 0.0001). In multivariable analyses, higher odds of DKA were found in females (odds ratio [OR] 1.23, 99% CI 1.10-1.37), ethnic minorities (OR 1.27, 99% CI 1.11-1.44), and HbA1c >=7.5% (>=58 mmol/mol) (OR 2.54, 99% CI 2.09-3.09 for HbA1c from 7.5 to <9% [58 to <75 mmol/mol] and OR 8.74, 99% CI 7.18-10.63 for HbA1c >=9.0% [>=75 mmol/mol]). CONCLUSIONS: These multinational data demonstrate high rates of DKA in childhood type 1 diabetes across three registries/audits and five nations. Females, ethnic minorities, and HbA1c above target were all associated with an increased risk of DKA. Targeted DKA prevention programs could result in substantial health care cost reduction and reduced patient morbidity and mortality. PMID- 26283738 TI - Assessing rates of hypoglycemia as an end point in clinical trials. PMID- 26283739 TI - Safety and Efficacy of Liraglutide in Patients With Type 2 Diabetes and End-Stage Renal Disease: An Investigator-Initiated, Placebo-Controlled, Double-Blind, Parallel-Group, Randomized Trial. AB - OBJECTIVE: To evaluate parameters related to safety and efficacy of liraglutide in patients with type 2 diabetes and dialysis-dependent end-stage renal disease (ESRD). RESEARCH DESIGN AND METHODS: Twenty-four patients with type 2 diabetes and ESRD and 23 control subjects with type 2 diabetes and normal kidney function were randomly allocated to 12 weeks of double-blind liraglutide (titrated to a maximum dose of 1.8 mg) or placebo treatment (1:1) injected subcutaneously once daily as add on to ongoing antidiabetic treatment. Dose-corrected plasma trough liraglutide concentration was evaluated at the final trial visit as the primary outcome measure using a linear mixed model. RESULTS: Twenty patients with ESRD (1:1 for liraglutide vs. placebo) and 20 control subjects (1:1) completed the study period. Dose-corrected plasma trough liraglutide concentration at the final visit was increased by 49% (95% CI 6-109, P = 0.02) in the group with ESRD compared with the control group. Initial and temporary nausea and vomiting occurred more frequently among liraglutide-treated patients with ESRD compared with control subjects (P < 0.04). Glycemic control tended to improve during the study period in both liraglutide-treated groups as assessed by daily blood glucose measurements (P < 0.01), and dose of baseline insulin was reduced in parallel (P < 0.04). Body weight was reduced in both liraglutide-treated groups ( 2.4 +/- 0.8 kg [mean +/- SE] in the group with ESRD, P = 0.22; -2.9 +/- 1.0 kg in the control group, P = 0.03). CONCLUSIONS: Plasma liraglutide concentrations increased during treatment in patients with type 2 diabetes and ESRD, who experienced more gastrointestinal side effects. Reduced treatment doses and prolonged titration period may be advisable. PMID- 26283740 TI - Trichomonas vaginalis and Mycoplasma genitalium: age-specific prevalence and disease burden in men attending a sexually transmitted infections clinic in Amsterdam, the Netherlands. AB - BACKGROUND: Men are not routinely tested for Trichomonas vaginalis (TV) and Mycoplasma genitalium (MG) in the Netherlands and, therefore, very few studies have looked into their prevalence and/or role in urogenital complaints in the Dutch male population. OBJECTIVE: To describe the age-specific prevalence and disease burden of TV and MG, and their co-occurrence with Chlamydia trachomatis (CT), in men attending the sexually transmitted infections (STI) clinic in Amsterdam, the Netherlands. METHODS: Urine samples and clinical data were collected from 526 men who have sex with women (MSW) and 678 men who have sex with men (MSM) attending the STI clinic. To investigate age as a risk factor, we oversampled older men. Urine samples were tested for TV and MG using molecular tests. RESULTS: The overall prevalence was 0.5% (6/1204) for TV and 3.1% (37/1204) for MG. Four out of the six TV cases were older than 40 years and all TV cases were MSW. No age trend was observed for MG, nor did MG prevalence differ between MSW and MSM. Co-infections between TV or MG and CT were rare. TV infection did not associate with urogenital symptoms, whereas 5.9% of men reporting urogenital symptoms were infected with MG. CONCLUSIONS: TV infection was rare in men, asymptomatic and was limited to the heterosexual network. MG infection was relatively common and equally prevalent among MSW and MSM of all ages. Most MG infections remained asymptomatic, however, our results suggest that up to 6% of urogenital complaints could be explained by MG infection. PMID- 26283741 TI - Dengue Virus Infection Triggering Thrombotic Thrombocytopenic Purpura in Pregnancy. AB - We report a case of thrombotic thrombocytopenic purpura (TTP) that immediately followed symptomatic dengue virus infection in a pregnant lady. The patient developed dengue fever at 16 weeks of gestation, resulting in spontaneous abortion. Subsequently, fever reappeared with persistent thrombocytopenia and jaundice. Investigations revealed microangiopathic hemolysis; there was no evidence of disseminated intravascular coagulation. The TTP episode resolved after six cycles of therapeutic plasma exchange with fresh-frozen plasma. An ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif 13 repeats) activity assay, done during convalescence, showed normal activity. The patient had an uneventful second pregnancy and has remained free of TTP recurrence for more than 2 years now. We review the pathophysiological basis of TTP in dengue infection, and suggest that jaundice with disproportionate elevation of serum aspartate aminotransferase level in a patient with dengue should arouse the suspicion of TTP. PMID- 26283742 TI - Changes in Genetic Diversity from Field to Laboratory During Colonization of Anopheles darlingi Root (Diptera: Culicidae). AB - The process of colonizing any arthropod species, including vector mosquitoes, necessarily involves adaptation to laboratory conditions. The adaptation and evolution of colonized mosquito populations needs consideration when such colonies are used as representative models for pathogen transmission dynamics. A recently established colony of Anopheles darlingi, the primary malaria vector in Amazonian South America, was tested for genetic diversity and bottleneck after 21 generations, using microsatellites. As expected, laboratory An. darlingi had fewer private and rare alleles (frequency < 0.05), decreased observed heterozygosity, and more common alleles (frequency > 0.50), but no significant evidence of a bottleneck, decrease in total alleles, or increase in inbreeding compared with field specimens (founder population). Low-moderate differentiation between field and laboratory populations was detected. With these findings, and the documented inherent differences between laboratory and field populations, results of pathogen transmission studies using this An. darlingi colony need to be interpreted cautiously. PMID- 26283743 TI - Clinical Efficacy of Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Plasmodium falciparum Malaria at the China-Myanmar Border. AB - Artemisinin-based combination therapies (ACTs) are currently used as the first line therapy for uncomplicated Plasmodium falciparum malaria. However, the recent emergence and/or spread of artemisinin resistance in parts of Greater Mekong Subregion (GMS) of southeast Asia requires close monitoring of the therapeutic efficacy of ACTs. This study was conducted from March 2012 to December 2013 in four clinics and seven villages along the China-Myanmar border. A total of 109 patients with uncomplicated falciparum malaria were treated with dihydroartemisinin-piperaquine (DP) and followed up on days 1, 2, 3, 7, 14, 21, 28, and 42 after treatment. A total of 71 patients (22 children and 49 adults) completed the 42-day follow-up. DP remained highly efficacious for treatment of uncomplicated falciparum malaria with an overall 42-day cure rate of 100%. The day 3 parasite-positive rate was 7.04% (5/71). Within 14 days of treatment, a total of 13 (18.31%) patients had detectable gametocytes and a large proportion of these were persistent from the first three days of treatment. The presence of gametocytes in patients through 14 days after DP treatment suggests that the incorporation of a single dose of primaquine for clearing gametocytemia should be considered for blocking parasite transmission. PMID- 26283744 TI - Lymphatic Dissemination in Cutaneous Leishmaniasis Following Local Treatment. AB - Cutaneous leishmaniasis (CL) is diverse in its clinical presentation but usually demonstrates an erythematous, infiltrated, ulcerated, and crusted papule or nodule in exposed areas of the body. Rare clinical features have been reported including lymphatic dissemination, usually with subcutaneous nodules along lymphatic channels. Herein, we present six patients suffering from Old World CL with lymphatic dissemination characterized by sporotrichoid subcutaneous nodules along the lymphatic channels draining the primary lesion. Patients' history, clinical and laboratory findings were collected and summarized. Lymphatic dissemination of CL in our patients manifested as subcutaneous nodules without epidermal involvement within the axis of lymphatic drainage toward the regional lymph node, at times accompanied by regional lymphadenopathy. In all patients, the lymphatic dissemination was not present at initial diagnosis of CL, appearing only after local (topical or intralesional) treatment was initiated. In three patients, the subcutaneous nodules resolved without systemic treatment. Lymphatic dissemination of Old World CL is not uncommon and may possibly be triggered by local treatment. It should be recognized by dermatologists, especially those working in endemic areas. Systemic treatment may be not necessary since spontaneous resolution may occur. PMID- 26283745 TI - High Antimalarial Efficacy of Dihydroartemisinin-Piperaquine on the China-Myanmar Border: The Calm Before the Storm. PMID- 26283746 TI - Potential Impact of Seasonal Malaria Chemoprevention on the Acquisition of Antibodies Against Glutamate-Rich Protein and Apical Membrane Antigen 1 in Children Living in Southern Senegal. AB - Seasonal malaria chemoprevention (SMC) is defined as the intermittent administration of full treatment courses of an antimalarial drug to children during the peak of malaria transmission season with the aim of preventing malaria associated mortality and morbidity. SMC using sulfadoxine-pyrimethamine (SP) combined with amodiaquine (AQ) is a promising strategy to control malaria morbidity in areas of highly seasonal malaria transmission. However, a concern is whether SMC can delay the natural acquisition of immunity toward malaria parasites in areas with intense SMC delivery. To investigate this, total IgG antibody (Ab) responses to Plasmodium falciparum antigens glutamate-rich protein R0 (GLURP-R0) and apical membrane antigen 1 (AMA-1) were measured by enzyme linked immunosorbent assay in Senegalese children under the age of 10 years in 2010 living in Saraya and Velingara districts (with SMC using SP + AQ [SMC+] since 2007) and Tambacounda district (without SMC (SMC-)). For both P. falciparum antigens, total IgG response were significantly higher in the SMC- compared with the SMC+ group (for GLURP-R0, P < 0.001 and for AMA-1, P = 0.001). There was as well a nonsignificant tendency for higher percentage of positive responders in the SMC- compared with the SMC+ group (for GLURP-R0: 22.2% versus 14.4%, respectively [P = 0.06]; for AMA-1: 45.6% versus 40.0%, respectively [P = 0.24]). Results suggest that long-term malaria chemoprevention by SMC/SP + AQ have limited impact on the development of acquired immunity, as tested using the P. falciparum antigens GLURP-R0 and AMA-1. However, other factors, not measured in this study, may interfere as well. PMID- 26283747 TI - High Mobility and Low Use of Malaria Preventive Measures Among the Jarai Male Youth Along the Cambodia-Vietnam Border. AB - Malaria control along the Vietnam-Cambodia border presents a challenge for both countries' malaria elimination targets as the region is forested, inhabited by ethnic minority populations, and potentially characterized by early and outdoor malaria transmission. A mixed methods study assessed the vulnerability to malaria among the Jarai population living on both sides of the border in the provinces of Ratanakiri (Cambodia) and Gia Lai (Vietnam). A qualitative study generated preliminary hypotheses that were quantified in two surveys, one targeting youth (N = 498) and the other household leaders (N = 449). Jarai male youth, especially in Cambodia, had lower uptake of preventive measures (57.4%) and more often stayed overnight in the deep forest (35.8%) compared with the female youth and the adult population. Among male youth, a high-risk subgroup was identified that regularly slept at friends' homes or outdoors, who had fewer bed nets (32.5%) that were torn more often (77.8%). The vulnerability of Jarai youth to malaria could be attributed to the transitional character of youth itself, implying less fixed sleeping arrangements in nonpermanent spaces or non-bed sites. Additional tools such as long-lasting hammock nets could be suitable as they are in line with current practices. PMID- 26283748 TI - Use of Rapid Influenza Testing to Reduce Antibiotic Prescriptions Among Outpatients with Influenza-Like Illness in Southern Sri Lanka. AB - Acute respiratory tract infections (ARTIs) are a common reason for unnecessary antibiotic prescriptions worldwide. Our objective was to determine if providing access to rapid influenza test results could reduce antibiotic prescriptions for ARTIs in a resource-limited setting. We conducted a prospective, pre-post study from March 2013 to October 2014. Outpatients presenting to a hospital in Sri Lanka were surveyed for influenza-like illness-onset of fever >= 38.0 degrees C and cough in prior 7 days. Enrolled patients were administered a structured questionnaire, physical examination, and nasal/nasopharyngeal sampling for rapid influenza A/B testing. Influenza test results were released only during phase 2 (January-October 2014). We enrolled 571 patients with ILI-316 in phase 1 and 241 in phase 2. The proportion positive for influenza was 46.5% in phase 1 and 28.6% in phase 2, P < 0.001. Between phases, antibiotic prescriptions decreased from 81.3% to 69.3% (P = 0.001) among all patients and from 83.7% to 62.3% (P = 0.001) among influenza-positive patients. On multivariable analysis, a positive influenza result during phase 2 was associated with lower odds of antibiotic prescriptions (OR = 0.50, 95% CI = 0.26-0.95). This prospective study suggests that providing access to rapid influenza testing may reduce unnecessary antibiotic prescriptions in resource-limited settings. PMID- 26283749 TI - Patterns of Hepatosplenic Brucella Abscesses on Cross-Sectional Imaging: A Review of Clinical and Imaging Features. AB - While diffuse involvement of liver and spleen is frequently seen in brucellosis, suppurative abscesses caused by Brucella are less common but well described. With the increased availability of cross-sectional imaging techniques, reports have become more frequent. Four patients with hepatosplenic abscesses caused by Brucella spp. are described and included in a review of 115 previously published cases. Clinical characteristics and patterns on ultrasound (US) and computed tomography imaging were analyzed. Furthermore, the proportion of patients with brucellosis affected by suppurative hepatosplenic lesions was estimated. Hepatosplenic abscesses were seen in 1.2% of patients with brucellosis and were mostly caused by Brucella melitensis. Imaging analysis revealed two main distinct patterns. Solitary abscesses involving liver more frequently than spleen, and showing characteristic central calcifications, characterize the first pattern. Multiple smaller abscesses, frequent spleen involvement, and absence of calcifications characterize the second pattern. Blood and aspirate cultures were frequently negative, however, the positivity rate increased over the past years. Indirect Coombs test was positive in 96%. Half of the patients were cured by antibiotic treatment; case fatality in this series was 1.9%. Hepatosplenic abscesses due to Brucella infections have characteristic imaging findings. Clinicians should be aware of these and the proactive use of cross-sectional imaging, particularly US, should be encouraged in endemic regions. PMID- 26283750 TI - The High Burden of Malaria in Primary School Children in Southern Malawi. AB - Malaria among school children has received increased attention recently, yet there remain few detailed data on the health and educational burden of malaria, especially in southern Africa. This paper reports a survey among school children in 50 schools in Zomba District, Malawi. Children were assessed for Plasmodium infection, anemia, and nutritional status and took a battery of age-appropriate tests of attention, literacy, and numeracy. Overall, 60.0% of children were infected with Plasmodium falciparum, 32.4% were anemic and 32.4% reported sleeping under a mosquito net the previous night. Patterns of P. falciparum infection and anemia varied markedly by school. In multivariable analysis, higher odds of P. falciparum infection were associated with younger age and being stunted, whereas lower odds were associated with reported net use, higher parental education, and socioeconomic status. The odds of anemia were significantly associated with P. falciparum infection, with a dose-response relationship between density of infection and odds of anemia. No clear relationship was observed between health status and cognitive and educational outcomes. The high burden of malaria highlights the need to tackle malaria among school children. PMID- 26283751 TI - Seroprevalence of Trypanosoma cruzi Infection in Schoolchildren and in Pregnant Women from an Amazonian Region in Orellana Province, Ecuador. AB - Chagas disease is a parasitic disease caused by the protozoan parasite Trypanosoma cruzi and about 230,000 persons are estimated to be infected in Ecuador. However, limited studies have been performed in the Amazon region, on the eastern side of the country. We evaluated here the seroprevalence of Trypanosoma cruzi infection in 12 rural villages of the Loreto canton, Orellana Province in schoolchildren aged 5-15 years and in pregnant women. A total of 1,649 blood samples were tested for Trypanosoma cruzi antibodies by enzyme-linked immunosorbent assay and indirect hemaglutination, and discordant samples were tested by indirect immunofluorescence assay. We detected a seroprevalence of anti Trypanosoma cruzi antibodies of 1.3% in schoolchildren aged 5-15 years, indicating the persistence of a constant and active vectorial transmission in the Loreto County and confirming the need of the implementation of nonconventional vector control. We also observed a seroprevalence of 3.8% in pregnant women, indicating a clear risk of congenital transmission. Further studies should help define this risk more precisely and implement current international guidelines for the diagnosis, treatment, and care of these cases. PMID- 26283752 TI - Human Monkeypox in the Kivus, a Conflict Region of the Democratic Republic of the Congo. AB - Monkeypox (MPX) is a zoonotic Orthopoxvirus infection endemic in central and western Africa. Human MPX cases occur in the central and northern regions of the Democratic Republic of the Congo (DRC), and this is the first report of confirmed MPX cases in the forested areas of North and South Kivu Provinces, with a detailed epidemiological investigation for one case. The location of each case is within areas predicted to be suitable for MPX virus transmission based on an ecological niche model. Phylogenetic analysis places these viruses in the Congo Basin clade. PMID- 26283753 TI - Randomized Clinical Trial of Virtual Reality Simulation Training for Transvaginal Gynecologic Ultrasound Skills. AB - OBJECTIVES: To compare the impact of virtual reality simulation training and theoretical teaching on the ability of inexperienced trainees to produce adequate virtual transvaginal ultrasound images. METHODS: We conducted a randomized controlled trial with parallel groups. Participants included inexperienced residents starting a training program in Paris. The intervention consisted of 40 minutes of virtual reality simulation training using a haptic transvaginal simulator versus 40 minutes of conventional teaching including a conference with slides and videos and answers to the students' questions. The outcome was a 19 point image quality score calculated from a set of 4 images (sagittal and coronal views of the uterus and left and right ovaries) produced by trainees immediately after the intervention, using the same simulator on which a new virtual patient had been uploaded. Experts assessed the outcome on stored images, presented in a random order, 2 months after the trial was completed. They were blinded to group assignment. The hypothesis was an improved outcome in the intervention group. Randomization was 1 to 1. RESULTS: The mean score was significantly greater in the simulation group (n = 16; mean score, 12; SEM, 0.8) than the control group (n = 18; mean score, 9; SEM, 1.0; P= .0302). CONCLUSIONS: The quality of virtual vaginal images produced by inexperienced trainees was greater immediately after a single virtual reality simulation training session than after a single theoretical teaching session. PMID- 26283754 TI - What Is the Appropriate Use of Renal Sonography in an Inner-City Population With New-Onset Acute Kidney Injury? AB - OBJECTIVES: We aimed to determine the prevalence of hydronephrosis in patients who underwent renal sonography for new-onset acute kidney injury (AKI) and to identify clinical factors predictive of hydronephrosis. In patients with hydronephrosis, we sought to investigate how routine renal sonography affects patient treatment, including performance of interventional procedures. METHODS: A retrospective chart review identified 274 adults with AKI who underwent renal sonography at an urban teaching hospital from January through July 2011. The prevalence of hydronephrosis was determined. Electronic medical records were reviewed for comorbidities, including risk factors for hydronephrosis such as a pelvic mass, prior renal or pelvic surgery, and neurogenic bladder, and for subsequent interventions and outcomes. RESULTS: Sonography showed hydronephrosis in 28 patients (10%); 5 (18%) had subsequent interventions. In a multivariable logistic regression model with the outcome being hydronephrosis, all considered risk factors (pelvic mass, prior renal or pelvic surgery, and neurogenic bladder) were significantly associated with hydronephrosis (odds ratio, 6.4; 95% confidence interval, 2.7-15.4; P < .001) when adjusting for age and diabetes mellitus. Diabetes had a negative predictive value for hydronephrosis. No diabetic patients younger than 85 years and without clinical risk factors had hydronephrosis. CONCLUSIONS: Hydronephrosis is infrequently seen on sonograms in hospitalized patients with AKI who lack risk factors for urinary tract obstruction. Deferral of sonography pending a trial of medical treatment is safe and will reduce medical costs. Adoption of clinical guidelines to assess patients' risk levels for hydronephrosis is critical to avoid unnecessary imaging. PMID- 26283755 TI - Rapid Ultrasound in Shock (RUSH) Velocity-Time Integral: A Proposal to Expand the RUSH Protocol. AB - Ultrasound assessment of patients in shock is becoming the standard of care in emergency and critical care settings worldwide. One of the most common protocols used for this assessment is the rapid ultrasound in shock (RUSH) examination. The RUSH protocol is a rapid evaluation of cardiac function, key vascular structures, and likely sources of hypotension. Stroke volume is an established important value to assess in the setting of shock, allowing the provider to predict the patient's response to treatment. However, the calculation of stroke volume or its surrogates is not part of any protocol, including RUSH. We propose the addition of ultrasound calculation of stroke volume or surrogates to the RUSH protocol and provide support for its utility and relative ease of calculation. The resulting product would be the RUSH velocity-time integral protocol. PMID- 26283756 TI - B-Lines in Assessment of Pulmonary Hypertension in Patients With Interstitial Lung Diseases: Feasibility of Transthoracic Lung Sonographic Signs. AB - OBJECTIVES: This study was conducted to evaluate the value of sonographic B-lines (previously called "comet tail artifacts") in assessment of pulmonary hypertension in patients with interstitial lung diseases. METHODS: One hundred thirty-four patients with clinically diagnosed interstitial lung diseases complicated by pulmonary hypertension underwent transthoracic lung sonography and Doppler echocardiography for assessment of the presence of B-lines, the distance between them, and the pulmonary artery (PA) systolic pressure. A correlation analysis and a receiver operating characteristic curve analysis were performed. RESULTS: All patients had diffuse bilateral B-lines. The maximum number of B lines seen in any positive zone (not a summation) was significantly correlated with the severity of PA systolic pressure (r= 0.812; P< .0001), and a linear regression equation could be demonstrated: that is, y = 6.06 x + 17.57, where x and y represent the number of B-lines and PA systolic pressure, respectively. A cutoff of more than 4 B-lines seen in any positive zone had 89.5% sensitivity, 85.0% specificity, and 87.2% accuracy in predicting elevated PA pressure (>30 mm Hg). CONCLUSIONS: The number of B-lines is useful in assessment of pulmonary hypertension, especially when tricuspid regurgitation and pulmonary valve regurgitation do not exist or cannot be satisfactorily measured by Doppler echocardiography. PMID- 26283757 TI - Sonography for Assessing Dynamic Diaphragm Dysfunction in Acute Respiratory Distress. PMID- 26283759 TI - Axial myoclonus after ischemic stroke. PMID- 26283760 TI - Teaching NeuroImages: The lentiform fork sign: An MRI pattern of metformin associated encephalopathy. PMID- 26283758 TI - Effect of clopidogrel with aspirin on functional outcome in TIA or minor stroke: CHANCE substudy. AB - OBJECTIVE: We compared the effect of clopidogrel plus aspirin vs aspirin alone on functional outcome and quality of life in the Clopidogrel in High-risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial of aspirin clopidogrel vs aspirin alone after acute minor stroke or TIA. METHODS: Participants were assessed at 90 days for functional outcome using the modified Rankin Scale (mRS) and quality of life using the EuroQol-5 Dimension (EQ-5D). Poor functional outcome was defined as mRS score of 2-6 at 90 days and poor quality of life as EQ-5D index score of 0.5 or less. RESULTS: Poor functional outcome occurred in 254 patients (9.9%) in the clopidogrel-aspirin group, as compared with 299 (11.6%) in the aspirin group (p = 0.046). Poor quality of life occurred in 142 (5.5%) in the clopidogrel-aspirin group and in 175 (6.8%) in the aspirin group (p = 0.06). Disabling stroke at 90 days occurred in 166 (6.5%) in the clopidogrel-aspirin group and in 219 (8.5%) in the aspirin group (p = 0.01). In stratified analysis by subsequent stroke, there was no difference in 90-day functional outcome and quality of life between the 2 groups. CONCLUSIONS: In patients with minor stroke or TIA, the combination of clopidogrel and aspirin appears to be superior to aspirin alone in improving the 90-day functional outcome, and this is consistent with a reduction in the rate of disabling stroke in the dual antiplatelet arm. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with acute minor stroke or TIA, clopidogrel plus aspirin compared to aspirin alone improves 90-day functional outcome (absolute reduction of poor outcome 1.70%, 95% confidence interval 0.03%-3.42%). PMID- 26283761 TI - Vigabatrin retinal toxicity in children with infantile spasms: An observational cohort study. PMID- 26283762 TI - Clinical Reasoning: Worsening neurologic symptoms in a brain tumor patient. PMID- 26283764 TI - Daytime napping results in an underestimation of thermal strain during exercise in the heat: authors' response. PMID- 26283763 TI - Deep Sequencing of Three Loci Implicated in Large-Scale Genome-Wide Association Study Smoking Meta-Analyses. AB - INTRODUCTION: Genome-wide association study meta-analyses have robustly implicated three loci that affect susceptibility for smoking: CHRNA5?CHRNA3?CHRNB4, CHRNB3?CHRNA6 and EGLN2?CYP2A6. Functional follow-up studies of these loci are needed to provide insight into biological mechanisms. However, these efforts have been hampered by a lack of knowledge about the specific causal variant(s) involved. In this study, we prioritized variants in terms of the likelihood they account for the reported associations. METHODS: We employed targeted capture of the CHRNA5?CHRNA3?CHRNB4, CHRNB3?CHRNA6, and EGLN2?CYP2A6 loci and flanking regions followed by next-generation deep sequencing (mean coverage 78*) to capture genomic variation in 363 individuals. We performed single locus tests to determine if any single variant accounts for the association, and examined if sets of (rare) variants that overlapped with biologically meaningful annotations account for the associations. RESULTS: In total, we investigated 963 variants, of which 71.1% were rare (minor allele frequency < 0.01), 6.02% were insertion/deletions, and 51.7% were catalogued in dbSNP141. The single variant results showed that no variant fully accounts for the association in any region. In the variant set results, CHRNB4 accounts for most of the signal with significant sets consisting of directly damaging variants. CHRNA6 explains most of the signal in the CHRNB3?CHRNA6 locus with significant sets indicating a regulatory role for CHRNA6. Significant sets in CYP2A6 involved directly damaging variants while the significant variant sets suggested a regulatory role for EGLN2. CONCLUSIONS: We found that multiple variants implicating multiple processes explain the signal. Some variants can be prioritized for functional follow-up. PMID- 26283765 TI - Whole-Genome Comparison Uncovers Genomic Mutations between Group B Streptococci Sampled from Infected Newborns and Their Mothers. AB - Streptococcus agalactiae (group B Streptococcus or GBS), a commensal of the human gut and genitourinary tract, is a leading cause of neonatal infections, in which vertical transmission from mother to child remains the most frequent route of contamination. Here, we investigated whether the progression of GBS from carriage to disease is associated with genomic adaptation. Whole-genome comparison of 47 GBS samples from 19 mother-child pairs uncovered 21 single nucleotide polymorphisms (SNPs) and seven insertions/deletions. Of the SNPs detected, 16 appear to have been fixed in the population sampled whereas five mutations were found to be polymorphic. In the infant strains, 14 mutations were detected, including two independently fixed variants affecting the covRS locus, which is known to encode a major regulatory system of virulence. A one-nucleotide insertion was also identified in the promoter region of the highly immunogenic surface protein Rib gene. Gene expression analysis after incubation in human blood showed that these mutations influenced the expression of virulence associated genes. Additional identification of three mutated strains in the mothers' milk raised the possibility of the newborns also being a source of contamination for their mothers. Overall, our work showed that GBS strains in carriage and disease scenarios might undergo adaptive changes following colonization. The types and locations of the mutations found, together with the experimental results showing their phenotypic impact, suggest that those in a context of infection were positively selected during the transition of GBS from commensal to pathogen, contributing to an increased capacity to cause disease. IMPORTANCE: Group B Streptococcus (GBS) is a major pathogen responsible for neonatal infections. Considering that its colonization of healthy adults is mostly asymptomatic, the mechanisms behind its switch from a commensal to an invasive state are largely unknown. In this work, we compared the genomic profile of GBS samples causing infections in newborns with that of the GBS colonizing their mothers. Multiple mutations were detected, namely, within key virulence factors, including the response regulator CovR and surface protein Rib, potentially affecting the pathogenesis of GBS. Their overall impact was supported by differences in the expression of virulence-associated genes in human blood. Our results suggest that during GBS's progression to disease, particular variants are positively selected, contributing to the ability of this bacterium to infect its host. PMID- 26283766 TI - Mechanistic Insight into Trimethylamine N-Oxide Recognition by the Marine Bacterium Ruegeria pomeroyi DSS-3. AB - Trimethylamine N-oxide (TMAO) is an important nitrogen source for marine bacteria. TMAO can also be metabolized by marine bacteria into volatile methylated amines, the precursors of the greenhouse gas nitrous oxide. However, it was not known how TMAO is recognized and imported by bacteria. Ruegeria pomeroyi DSS-3, a marine Roseobacter, has an ATP-binding cassette transporter, TmoXWV, specific for TMAO. TmoX is the substrate-binding protein of the TmoXWV transporter. In this study, the substrate specificity of TmoX of R. pomeroyi DSS 3 was characterized. We further determined the structure of the TmoX/TMAO complex and studied the TMAO-binding mechanism of TmoX by biochemical, structural, and mutational analyses. A Ca(2+) ion chelated by an extended loop in TmoX was shown to be important for maintaining the stability of TmoX. Molecular dynamics simulations indicate that TmoX can alternate between "open" and "closed" states for binding TMAO. In the substrate-binding pocket, four tryptophan residues interact with the quaternary amine of TMAO by cation-pi interactions, and Glu131 forms a hydrogen bond with the polar oxygen atom of TMAO. The pi-pi stacking interactions between the side chains of Phe and Trp are also essential for TMAO binding. Sequence analysis suggests that the TMAO-binding mechanism of TmoX may have universal significance in marine bacteria, especially in the marine Roseobacter clade. This study sheds light on how marine microorganisms utilize TMAO. IMPORTANCE: Trimethylamine N-oxide (TMAO) is an important nitrogen source for marine bacteria. The products of TMAO metabolized by bacteria are part of the precursors of the greenhouse gas nitrous oxide. It is unclear how TMAO is recognized and imported by bacteria. TmoX is the substrate-binding protein of a TMAO-specific transporter. Here, the substrate specificity of TmoX of Ruegeria pomeroyi DSS-3 was characterized. The TMAO-binding mechanism of TmoX was studied by biochemical, structural, and mutational analyses. Moreover, our results suggest that the TMAO-binding mechanism may have universal significance in marine bacteria. This study sheds light on how marine microorganisms utilize TMAO and should lead to a better understanding of marine nitrogen cycling. PMID- 26283767 TI - The Sulfolobus solfataricus GINS Complex Stimulates DNA Binding and Processive DNA Unwinding by Minichromosome Maintenance Helicase. AB - GINS is a key component of the eukaryotic Cdc45-minichromosome maintenance (MCM) GINS (CMG) complex, which unwinds duplex DNA at the moving replication fork. Archaeal GINS complexes have been shown to stimulate the helicase activity of their cognate MCM mainly by elevating its ATPase activity. Here, we report that GINS from the thermoacidophilic crenarchaeon Sulfolobus solfataricus (SsoGINS) is capable of DNA binding and binds preferentially to single-stranded DNA (ssDNA) over double-stranded DNA (dsDNA). Notably, SsoGINS binds more strongly to dsDNA with a 5' ssDNA tail than to dsDNA with a 3' tail and more strongly to an ssDNA fragment blocked at the 3' end than to one at the 5' end with a biotin streptavidin (SA) complex, suggesting the ability of the protein complex to slide in a 5'-to-3' direction along ssDNA. DNA-bound SsoGINS enhances DNA binding by SsoMCM. Furthermore, SsoGINS increases the helicase activity of SsoMCM. However, the ATPase activity of SsoMCM is not affected by SsoGINS. Our results suggest that SsoGINS facilitates processive DNA unwinding by SsoMCM by enhancing the binding of the helicase to DNA. We propose that SsoGINS stabilizes the interaction of SsoMCM with the replication fork and moves along with the helicase as the fork progresses. IMPORTANCE: GINS is a key component of the eukaryotic Cdc45-MCM-GINS complex, a molecular motor that drives the unwinding of DNA in front of the replication fork. Archaea also encode GINS, which interacts with MCM, the helicase. But how archaeal GINS serves its role remains to be understood. In this study, we show that GINS from the hyperthermophilic archaeon Sulfolobus solfataricus is able to bind to DNA and slide along ssDNA in a 5'-to 3' direction. Furthermore, Sulfolobus GINS enhances DNA binding by MCM, which slides along ssDNA in a 3'-to-5' direction. Taken together, these results suggest that Sulfolobus GINS may stabilize the interaction of MCM with the moving replication fork, facilitating processive DNA unwinding. PMID- 26283768 TI - The Absence of Pupylation (Prokaryotic Ubiquitin-Like Protein Modification) Affects Morphological and Physiological Differentiation in Streptomyces coelicolor. AB - Protein turnover is essential in all living organisms for the maintenance of normal cell physiology. In eukaryotes, most cellular protein turnover involves the ubiquitin-proteasome pathway, in which proteins tagged with ubiquitin are targeted to the proteasome for degradation. In contrast, most bacteria lack a proteasome but harbor proteases for protein turnover. However, some actinobacteria, such as mycobacteria, possess a proteasome in addition to these proteases. A prokaryotic ubiquitination-like tagging process in mycobacteria was described and was named pupylation: proteins are tagged with Pup (prokaryotic ubiquitin-like protein) and directed to the proteasome for degradation. We report pupylation in another actinobacterium, Streptomyces coelicolor. Both the morphology and life cycle of Streptomyces species are complex (formation of a substrate and aerial mycelium followed by sporulation), and these bacteria are prolific producers of secondary metabolites with important medicinal and agricultural applications. The genes encoding the pupylation system in S. coelicolor are expressed at various stages of development. We demonstrated that pupylation targets numerous proteins and identified 20 of them. Furthermore, we established that abolition of pupylation has substantial effects on morphological and metabolic differentiation and on resistance to oxidative stress. In contrast, in most cases, a proteasome-deficient mutant showed only modest perturbations under the same conditions. Thus, the phenotype of the pup mutant does not appear to be due solely to defective proteasomal degradation. Presumably, pupylation has roles in addition to directing proteins to the proteasome. IMPORTANCE: Streptomyces spp. are filamentous and sporulating actinobacteria, remarkable for their morphological and metabolic differentiation. They produce numerous bioactive compounds, including antifungal, antibiotic, and antitumor compounds. There is therefore considerable interest in understanding the mechanisms by which Streptomyces species regulate their complex physiology and production of bioactive compounds. We studied the role in Streptomyces of pupylation, a posttranslational modification that tags proteins that are then directed to the proteasome for degradation. We demonstrated that the absence of pupylation had large effects on morphological differentiation, antibiotic production, and resistance to oxidative stress in S. coelicolor. The phenotypes of pupylation and proteasome-defective mutants differed and suggest that pupylation acts in a proteasome-independent manner in addition to its role in proteasomal degradation. PMID- 26283769 TI - The Bacterial Tyrosine Kinase Activator TkmA Contributes to Biofilm Formation Largely Independently of the Cognate Kinase PtkA in Bacillus subtilis. AB - In Bacillus subtilis, biosynthesis of exopolysaccharide (EPS), a key biofilm matrix component, is regulated at the posttranslational level by the bacterial tyrosine kinase (BY-kinase) EpsB. EpsB, in turn, relies on the cognate kinase activator EpsA for activation. A concerted role of a second BY-kinase-kinase activator pair, PtkA and TkmA, respectively in biofilm formation was also indicated in previous studies. However, the exact functions of PtkA and TkmA in biofilm formation remain unclear. In this work, we show that the kinase activator TkmA contributes to biofilm formation largely independently of the cognate kinase, PtkA. We further show that the biofilm defect caused by a DeltatkmA mutation can be rescued by complementation by epsA, suggesting a functional overlap between TkmA and EpsA and providing a possible explanation for the role of TkmA in biofilm formation. We also show that the importance of TkmA in biofilm formation depends largely on medium conditions; the biofilm defect of DeltatkmA is very severe in the biofilm medium LBGM (lysogenic broth [LB] supplemented with 1% [vol/vol] glycerol and 100 MUM MnSO4) but marginal in another commonly used biofilm medium, MSgg (5 mM potassium phosphate [pH 7.0], MOPS [100 mM morpholinepropanesulfonic acid] [pH 7.0], 2 mM MgCl2, 700 MUM CaCl2, 50 MUM MnCl2, 50 MUM FeCl3, 1 MUM ZnCl2, 2 MUM thiamine, 0.5% glycerol, 0.5% glutamic acid, 50 MUg/ml tryptophan, 50 MUg/ml threonine, and 50 MUg/ml phenylalanine). The molecular basis for the medium dependence is likely due to differential expression of tkmA and epsA in the two different media and complex regulation of these genes by both Spo0A and DegU. Our studies provide genetic evidence for possible cross talk between a BY-kinase activator (TkmA) and a noncognate kinase (EpsB) and an example of how environmental conditions may influence such cross talk in regulating biofilm formation in B. subtilis. IMPORTANCE: In bacteria, biosynthesis of secreted polysaccharides is often regulated by bacterial tyrosine kinases (BY-kinases). BY-kinases, in turn, rely on cognate kinase activators for activation. In this study, we investigated the role of a BY-kinase activator in biofilm formation in Bacillus subtilis. We present evidence that different BY kinase activators may functionally overlap each other, as well as an example of how activities of the BY-kinase activators may be highly dependent on environmental conditions. Our study broadens the understanding of the complexity of regulation of the BY-kinases/kinase activators and the influence on bacterial cell physiology. PMID- 26283770 TI - A Cardiolipin-Deficient Mutant of Rhodobacter sphaeroides Has an Altered Cell Shape and Is Impaired in Biofilm Formation. AB - Cell shape has been suggested to play an important role in the regulation of bacterial attachment to surfaces and the formation of communities associated with surfaces. We found that a cardiolipin synthase (Deltacls) mutant of the rod shaped bacterium Rhodobacter sphaeroides--in which synthesis of the anionic, highly curved phospholipid cardiolipin (CL) is reduced by 90%--produces ellipsoid shaped cells that are impaired in biofilm formation. Reducing the concentration of CL did not cause significant defects in R. sphaeroides cell growth, swimming motility, lipopolysaccharide and exopolysaccharide production, surface adhesion protein expression, and membrane permeability. Complementation of the CL deficient mutant by ectopically expressing CL synthase restored cells to their rod shape and increased biofilm formation. Treating R. sphaeroides cells with a low concentration (10 MUg/ml) of the small-molecule MreB inhibitor S-(3,4 dichlorobenzyl)isothiourea produced ellipsoid-shaped cells that had no obvious growth defect yet reduced R. sphaeroides biofilm formation. This study demonstrates that CL plays a role in R. sphaeroides cell shape determination, biofilm formation, and the ability of the bacterium to adapt to its environment. IMPORTANCE: Membrane composition plays a fundamental role in the adaptation of many bacteria to environmental stress. In this study, we build a new connection between the anionic phospholipid cardiolipin (CL) and cellular adaptation in Rhodobacter sphaeroides. We demonstrate that CL plays a role in the regulation of R. sphaeroides morphology and is important for the ability of this bacterium to form biofilms. This study correlates CL concentration, cell shape, and biofilm formation and provides the first example of how membrane composition in bacteria alters cell morphology and influences adaptation. This study also provides insight into the potential of phospholipid biosynthesis as a target for new chemical strategies designed to alter or prevent biofilm formation. PMID- 26283771 TI - A Burkholderia thailandensis Acyl-Homoserine Lactone-Independent Orphan LuxR Homolog That Activates Production of the Cytotoxin Malleilactone. AB - Burkholderia thailandensis has three acyl-homoserine lactone (AHL) LuxR-LuxI quorum-sensing circuits and two orphan LuxR homologs. Orphans are LuxR-type transcription factors that do not have cognate LuxI-type AHL synthases. One of the orphans, MalR, is genetically linked to the mal gene cluster, which encodes enzymes required for production of the cytotoxic polyketide malleilactone. Under normal laboratory conditions the mal gene cluster is silent; however, antibiotics like trimethoprim induce mal transcription. We show that trimethoprim-dependent induction of the mal genes requires MalR. MalR has all of the conserved amino acid residues characteristic of AHL-responsive LuxR homologs, but in B. thailandensis, MalR activation of malleilactone synthesis genes is not responsive to AHLs. MalR can activate transcription from the mal promoter in E. coli without addition of AHLs or trimethoprim. Expression of malR in B. thailandensis is induced by trimethoprim. Our data indicate that MalR binds to a lux box-like element in the mal promoter and activates transcription of the mal genes in an AHL-independent manner. Antibiotics like trimethoprim appear to activate mal gene expression indirectly by somehow activating malR expression. MalR activation of the mal genes represents an example of a LuxR homolog that is not a receptor for an AHL quorum-sensing signal. Our evidence is consistent with the idea that mal gene activation depends solely on sufficient transcription of the malR gene. IMPORTANCE: LuxR proteins are transcription factors that are typically activated by acyl-homoserine lactone (AHL) signals. We demonstrate that a conserved LuxR family protein, MalR, activates genes independently of AHLs. MalR is required for transcription of genes coding for synthesis of the cytotoxic polyketide malleilactone. These genes are not expressed when cells are grown under normal laboratory conditions. In laboratory culture, MalR induction of malleilactone requires certain antibiotics, such as trimethoprim, which increase malR expression by an unknown mechanism. At sufficient levels of malR expression, MalR functions independently of any external signal. Our findings show that MalR is an activator of the silent malleilactone biosynthesis genes and that MalR functions independently of AHLs. PMID- 26283772 TI - Regulation of DNA Replication Initiation by Chromosome Structure. AB - Recent advancements in fluorescence imaging have shown that the bacterial nucleoid is surprisingly dynamic in terms of both behavior (movement and organization) and structure (density and supercoiling). Links between chromosome structure and replication initiation have been made in a number of species, and it is universally accepted that favorable chromosome structure is required for initiation in all cells. However, almost nothing is known about whether cells use changes in chromosome structure as a regulatory mechanism for initiation. Such changes could occur during natural cell cycle or growth phase transitions, or they could be manufactured through genetic switches of topoisomerase and nucleoid structure genes. In this review, we explore the relationship between chromosome structure and replication initiation and highlight recent work implicating structure as a regulatory mechanism. A three-component origin activation model is proposed in which thermal and topological structural elements are balanced with trans-acting control elements (DnaA) to allow efficient initiation control under a variety of nutritional and environmental conditions. Selective imbalances in these components allow cells to block replication in response to cell cycle impasse, override once-per-cell-cycle programming during growth phase transitions, and promote reinitiation when replication forks fail to complete. PMID- 26283773 TI - From Homodimer to Heterodimer and Back: Elucidating the TonB Energy Transduction Cycle. AB - The TonB system actively transports large, scarce, and important nutrients through outer membrane (OM) transporters of Gram-negative bacteria using the proton gradient of the cytoplasmic membrane (CM). In Escherichia coli, the CM proteins ExbB and ExbD harness and transfer proton motive force energy to the CM protein TonB, which spans the periplasmic space and cyclically binds OM transporters. TonB has two activity domains: the amino-terminal transmembrane domain with residue H20 and the periplasmic carboxy terminus, through which it binds to OM transporters. TonB is inactivated by all substitutions at residue H20 except H20N. Here, we show that while TonB trapped as a homodimer through its amino-terminal domain retained full activity, trapping TonB through its carboxy terminus inactivated it by preventing conformational changes needed for interaction with OM transporters. Surprisingly, inactive TonB H20A had little effect on homodimerization through the amino terminus and instead decreased TonB carboxy-terminal homodimer formation prior to reinitiation of an energy transduction cycle. That result suggested that the TonB carboxy terminus ultimately interacts with OM transporters as a monomer. Our findings also suggested the existence of a separate equimolar pool of ExbD homodimers that are not in contact with TonB. A model is proposed where interaction of TonB homodimers with ExbD homodimers initiates the energy transduction cycle, and, ultimately, the ExbD carboxy terminus modulates interactions of a monomeric TonB carboxy terminus with OM transporters. After TonB exchanges its interaction with ExbD for interaction with a transporter, ExbD homodimers undergo a separate cycle needed to re-energize them. IMPORTANCE: Canonical mechanisms of active transport across cytoplasmic membranes employ ion gradients or hydrolysis of ATP for energy. Gram-negative bacterial outer membranes lack these resources. The TonB system embodies a novel means of active transport across the outer membrane for nutrients that are too large, too scarce, or too important for diffusion-limited transport. A proton gradient across the cytoplasmic membrane is converted by a multiprotein complex into mechanical energy that drives high-affinity active transport across the outer membrane. This system is also of interest since one of its uses in pathogenic bacteria is for competition with the host for the essential element iron. Understanding the mechanism of the TonB system will allow design of antibiotics targeting iron acquisition. PMID- 26283774 TI - Regulation of Nitrite Stress Response in Desulfovibrio vulgaris Hildenborough, a Model Sulfate-Reducing Bacterium. AB - Sulfate-reducing bacteria (SRB) are sensitive to low concentrations of nitrite, and nitrite has been used to control SRB-related biofouling in oil fields. Desulfovibrio vulgaris Hildenborough, a model SRB, carries a cytochrome c-type nitrite reductase (nrfHA) that confers resistance to low concentrations of nitrite. The regulation of this nitrite reductase has not been directly examined to date. In this study, we show that DVU0621 (NrfR), a sigma54-dependent two component system response regulator, is the positive regulator for this operon. NrfR activates the expression of the nrfHA operon in response to nitrite stress. We also show that nrfR is needed for fitness at low cell densities in the presence of nitrite because inactivation of nrfR affects the rate of nitrite reduction. We also predict and validate the binding sites for NrfR upstream of the nrfHA operon using purified NrfR in gel shift assays. We discuss possible roles for NrfR in regulating nitrate reductase genes in nitrate-utilizing Desulfovibrio spp. IMPORTANCE: The NrfA nitrite reductase is prevalent across several bacterial phyla and required for dissimilatory nitrite reduction. However, regulation of the nrfA gene has been studied in only a few nitrate utilizing bacteria. Here, we show that in D. vulgaris, a bacterium that does not respire nitrate, the expression of nrfHA is induced by NrfR upon nitrite stress. This is the first report of regulation of nrfA by a sigma54-dependent two component system. Our study increases our knowledge of nitrite stress responses and possibly of the regulation of nitrate reduction in SRB. PMID- 26283775 TI - Congenital Heart Defects and Receipt of Special Education Services. AB - BACKGROUND: We investigated the prevalence of receipt of special education services among children with congenital heart defects (CHDs) compared with children without birth defects. METHODS: Children born from 1982 to 2004 in metropolitan Atlanta with CHDs (n = 3744) were identified from a population-based birth defect surveillance program; children without birth defects (n = 860 715) were identified from birth certificates. Cohorts were linked to special education files for the 1992-2012 school years to identify special education services. Children with noncardiac defects or genetic syndromes were excluded; children with CHDs were classified by presence or absence of critical CHDs (ie, CHDs requiring intervention by age one year). We evaluated the prevalence of receipt of special education services and prevalence rate ratios using children without birth defects as a reference. RESULTS: Compared with children without birth defects, children with CHDs were 50% more likely to receive special education services overall (adjusted prevalence rate ratio [aPRR] = 1.5; 95% confidence interval [CI]: 1.4-1.7). Specifically, they had higher prevalence of several special education categories including: intellectual disability (aPRR = 3.8; 95% CI: 2.8-5.1), sensory impairment (aPRR = 3.0; 95% CI: 1.8-5.0), other health impairment (aPRR = 2.8; 95% CI: 2.2-3.5), significant developmental delay (aPRR = 1.9; 95% CI: 1.3-2.8), and specific learning disability (aPRR = 1.4; 95% CI: 1.1 1.7). For most special education services, the excess prevalence did not vary by presence of critical CHDs. CONCLUSIONS: Children with CHDs received special education services more often than children without birth defects. These findings highlight the need for special education services and the importance of developmental screening for all children with CHDs. PMID- 26283777 TI - Risk of Sensorineural Hearing Loss and Bilirubin Exchange Transfusion Thresholds. AB - BACKGROUND AND OBJECTIVES: High bilirubin levels are associated with sensorineural hearing loss (SNHL). However, few large studies of relative and excess risk exist. We sought to quantify the risk of SNHL in newborns who had bilirubin levels at or above American Academy of Pediatrics exchange transfusion thresholds (ETT). METHODS: Infants born at >=35 weeks gestation in 15 Kaiser Permanente Northern California hospitals from 1995-2011 were eligible (N = 525 409). We used a nested double cohort design. The exposed cohort included subjects with >=1 bilirubin level at or above ETT. The unexposed cohort was a 3.6% random sample of subjects with all bilirubin levels below ETT (10 unexposed per exposed). An audiologist, blinded to bilirubin levels, reviewed the charts of children in whom SNHL had been diagnosed before age 8 years to confirm the diagnosis. We calculated Cox proportional hazard ratios for time to diagnosis of SNHL. RESULTS: SNHL was confirmed in 11 (0.60%) of the 1834 exposed subjects and in 43 (0.23%) of the 19 004 unexposed. Only bilirubin levels >=10 mg/dL above ETT were associated with a statistically significant increased risk of SNHL (hazard ratio: 36 [95% confidence interval (CI): 13 to 101]). Likewise, only bilirubin levels >=35 mg/dL were associated with a statistically significant increased risk of SNHL (hazard ratio: 91 [95% CI: 32 to 255]). For subjects with total serum bilirubin levels 0 to 4.9 mg/dL above ETT, the upper limit of the 95% CI for excess risk was 0.5%. CONCLUSIONS: Only bilirubin levels well above ETT were associated with SNHL. At lower bilirubin levels, the excess risk of SNHL was low. PMID- 26283776 TI - Is a New Protocol for Acute Lymphoblastic Leukemia Research or Standard Therapy? AB - In the United States, doctors generally develop new cancer chemotherapy for children by testing innovative chemotherapy protocols against existing protocols in prospective randomized trials. In the Netherlands, children with leukemia are treated by protocols that are agreed upon by the Dutch Childhood Oncology Group. Periodically, the Dutch Childhood Oncology Group revises its protocols. Sometimes, these revisions are categorized as research, sometimes as treatment. In this Ethics Rounds, we analyze whether enrollment in a new protocol ought to be considered research and, if so, we discuss the implications of that designation. Our discussion highlights the different ways different countries approach complex issues of research ethics. PMID- 26283778 TI - Unmet Health Care Need in US Adolescents and Adult Health Outcomes. AB - BACKGROUND: Adolescence is a formative period when health care services have a unique opportunity to influence later health outcomes. Unmet health care need in adolescence is known to be associated with poor contemporaneous health outcomes; it is unknown whether it predicts poor adult health outcomes. METHODS: We used nationally representative data from 14 800 subjects who participated in Wave I (mean age: 15.9 years [1994/1995]) and Wave IV (mean age: 29.6 years [2008]) of the National Longitudinal Study of Adolescent to Adult Health. Logistic regression models were used to estimate the association between unmet health care need in adolescence and 5 self-reported measures of adult health (fair/poor general health, functional impairment, time off work/school, depressive symptoms, and suicidal ideation). Models were adjusted for baseline health, insurance category, age, gender, race/ethnicity, household income, and parental education. RESULTS: Unmet health care need was reported by 19.2% of adolescents and predicted worse adult health: fair/poor general health (adjusted odds ratio [aOR]: 1.27 [95% confidence interval (CI): 1.00-1.60]); functional impairment (aOR: 1.52 [95% CI: 1.23-1.87]); depressive symptoms (aOR: 1.36 [95% CI: 1.13 1.64]); and suicidal ideation (aOR: 1.30 [95% CI: 1.03-1.68]). There was no significant association between unmet health care need and time off work/school (aOR: 1.13 [95% CI: 0.93-1.36]). Cost barriers accounted for only 14.8% of unmet health care need. The reason for unmet need was not significantly related to the likelihood of poor adult health outcomes. CONCLUSIONS: Reported unmet health care need in adolescence is common and is an independent predictor of poor adult health. Strategies to reduce unmet adolescent need should address health engagement and care quality, as well as cost barriers to accessing services. PMID- 26283779 TI - Folliculotropic Mycosis Fungoides as a Posttransplant Lymphoproliferative Disorder. AB - Posttransplant lymphoproliferative disorder (PTLD) is a known complication of solid organ transplantation. The majority are B cell in origin and related to Epstein-Barr virus infection. T-cell PTLD is much less common; most are Epstein Barr virus negative and have a worse prognosis. Primary cutaneous T-cell lymphoma (CTCL) as a presentation of PTLD is rare. CTCL has a less favorable prognosis in transplant patients compared with that in immune-competent patients. Herein, we report a case of a 13-year-old boy who developed folliculotropic mycosis fungoides, a rare subtype of CTCL, subsequent to renal transplantation. To our knowledge, this is the first report of this type of PTLD in a pediatric patient. PMID- 26283781 TI - Safety and Efficacy of High-Flow Nasal Cannula Therapy in Preterm Infants: A Meta analysis. AB - BACKGROUND AND OBJECTIVE: High-flow therapy is the most recent, and popular, mode of respiratory support in neonates. However, the evidence supporting its efficacy and safety has not yet been established. We conducted a systematic review and meta-analysis of clinical trials comparing efficacy and safety of high-flow therapy compared with other modes of noninvasive ventilation (NIV) in preterm infants. METHODS: Articles were indexed by using Medline, Embase, Scopus, OpenSIGLE, Health Management Information Consortium, and Cochrane Central Register of Controlled Trials. Randomized or quasi-randomized clinical trials involving preterm infants, comparing high-flow therapy with other modes of NIV, and reporting extractable data on relevant outcomes, were selected. Data on efficacy, safety, and other common neonatal outcomes were extracted on predesigned forms. RESULTS: In this analysis, we included 1112 preterm infants, participating in 9 clinical trials. High-flow therapy was similar in efficacy to other modes of NIV in preterm infants when used as primary support (odds ratio of failure of therapy, 1.02 [95% confidence interval: 0.55 to 1.88]), as well as after extubation (1.09 [0.58 to 2.02]). There were no significant differences in odds of death (0.48 [0.18 to 1.24]) between the groups. Preterm infants supported on high-flow had significantly lower odds of nasal trauma (0.13 [0.02 to 0.69]). CONCLUSIONS: High-flow therapy appears to be similar in efficacy and safety to other conventional modes of NIV in preterm infants. It is associated with significantly lower odds of nasal trauma. Caution needs to be exercised in extreme preterm infants because of the paucity of published data. PMID- 26283780 TI - The Need for Biological Outcomes to Complement Self-Report in Adolescent Research. PMID- 26283783 TI - Eye Protection and Risk of Eye Injuries in High School Field Hockey. AB - OBJECTIVE: To determine if injury rates among female field hockey players differ before and after implementation of a national mandate for protective eyewear (MPE). METHODS: We analyzed girls' field hockey exposure and injury data collected from national (High School Reporting Information Online [RIO]) and regional (Fairfax County Public Schools) high school sports injury databases in 2 seasons before (2009/10 and 2010/11) and 2 seasons after (2011/12 and 2012/13) a national MPE. RESULTS: The incidence of eye/orbital injuries was significantly higher in states without MPE (0.080 injuries per 1000 athletic exposures [AEs]) than in states with MPE (before the 2011/12 mandate) and the postmandate group (0.025 injuries per 1000 AEs) (odds ratio 3.20, 95% confidence interval 1.47 6.99, P = .003). There was no significant difference in concussion rates for the 2 groups (odds ratio 0.77, 95% confidence interval 0.58-1.02, P = .068). After the 2011/12 MPE, severe eye/orbital injuries (time loss >21 days) were reduced by 67%, and severe/medical disqualification head/face injuries were reduced by 70%. Concussion rates for field hockey (0.335 per 1000 AEs) rank third among girls' sports included in the High School RIO surveillance program. CONCLUSIONS: Among female high school field hockey players, MPE is associated with a reduced incidence of eye/orbital injuries and fewer severe eye/orbital and head/face injuries. Concussion rates did not change as a result of the national MPE. Concussion remains the most common injury involving the head and face among female field hockey players, prompting further inquiry into potential effects of adopting protective headgear/helmets. PMID- 26283784 TI - Early Cardiac Iron Overload in a Child on Treatment of Acute Lymphoblastic Leukemia. AB - An 11-year-old boy with Down syndrome and acute lymphoblastic leukemia developed hepatic dysfunction after only 10 months of treatment. MRI revealed severe iron deposition in the liver, pancreas, and heart. In stark contrast to what is seen in hemoglobinopathies, pancreatic and cardiac iron overload occurred with relatively low transfusion exposure and in a very short time period in this patient. Although extensive experience managing iron overload in hemoglobinopathies informs our approach in other diseases, it is clear that factors not present in hemoglobinopathies may be operative in patients with malignancy undergoing intense chemotherapy that lead to high levels of free iron and rapid loading of the heart and endocrine organs. PMID- 26283782 TI - Infection-Related Hospitalization in Childhood and Adult Metabolic Outcomes. AB - BACKGROUND AND OBJECTIVES: Identifying childhood determinants of adult cardiometabolic disease would facilitate early-life interventions. There are few longitudinal data on the contribution of childhood infections. Therefore, we investigated whether hospitalization with childhood infection is associated with adult anthropometric and metabolic outcomes in a large, well-phenotyped longitudinal cohort. METHODS: A total of 1376 subjects from the Cardiovascular Risk in Young Finns Study, aged 3 to 9 years at baseline (1980), who had lifetime data from birth onward on infection-related hospitalization (IRH) had repeated assessments through childhood and adolescence and at least once in adulthood (age 30-45 years in 2001-2011). Early childhood (<5 years), childhood/adolescence (5 18 years), adult (>18 years), and total lifetime IRHs were related to adiposity, BMI, and metabolic syndrome in adulthood. Analyses were adjusted for childhood and adulthood risk factors and potential confounders. RESULTS: Early-childhood IRH correlated with adverse adult but not childhood metabolic variables: increased BMI (P = .02) and metabolic syndrome (risk ratio: 1.56; 95% confidence interval: 1.03-2.35; P = .03), adjusted for age, gender, birth weight, childhood BMI and other risk factors, and family income. The age at which differences in adult BMI became persistent was related to age of IRH in childhood. The greatest increase in adult BMI occurred in those with >1 childhood IRH. CONCLUSIONS: Childhood IRH was independently associated with adverse adult metabolic variables. This finding suggests that infections and/or their treatment in childhood may contribute to causal pathways leading to adult cardiometabolic diseases. PMID- 26283785 TI - Matrix Metalloproteinase (MMP) Proteolysis of the Extracellular Loop of Voltage gated Sodium Channels and Potential Alterations in Pain Signaling. AB - Congenital insensitivity to pain (CIP) or congenital analgesia is a rare monogenic hereditary condition. This disorder is characterized by the inability to perceive any form of pain. Nonsense mutations in Nav.1.7, the main pain signaling voltage-gated sodium channel, lead to its truncations and, consequently, to the inactivation of the channel functionality. However, a non truncating homozygously inherited missense mutation in a Bedouin family with CIP (Nav1.7-R907Q) has also been reported. Based on our currently acquired in-depth knowledge of matrix metalloproteinase (MMP) cleavage preferences, we developed the specialized software that predicts the presence of the MMP cleavage sites in the peptide sequences. According to our in silico predictions, the peptide sequence of the exposed extracellular unstructured region linking the S5-S6 transmembrane segments in the DII domain of the human Nav1.7 sodium channel is highly sensitive to MMP-9 proteolysis. Intriguingly, the CIP R907Q mutation overlaps with the predicted MMP-9 cleavage site sequence. Using MMP-9 proteolysis of the wild-type, CIP, and control peptides followed by mass spectrometry of the digests, we demonstrated that the mutant sequence is severalfold more sensitive to MMP-9 proteolysis relative to the wild type. Because of the substantial level of sequence homology among sodium channels, our data also implicate MMP proteolysis in regulating the cell surface levels of the Nav1.7, Nav1.6, and Nav1.8 channels, but not Nav1.9. It is likely that the aberrantly accelerated MMP 9 proteolysis during neurogenesis is a biochemical rational for the functional inactivation in Nav1.7 and that the enhanced cleavage of the Nav1.7-R907Q mutant is a cause of CIP in the Bedouin family. PMID- 26283786 TI - Regulation of ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco) activase: product inhibition, cooperativity, and magnesium activation. AB - In many photosynthetic organisms, tight-binding Rubisco inhibitors are released by the motor protein Rubisco activase (Rca). In higher plants, Rca plays a pivotal role in regulating CO2 fixation. Here, the ATPase activity of 0.005 mm tobacco Rca was monitored under steady-state conditions, and global curve fitting was utilized to extract kinetic constants. The kcat was best fit by 22.3 +/- 4.9 min(-1), the Km for ATP by 0.104 +/- 0.024 mm, and the Ki for ADP by 0.037 +/- 0.007 mm. Without ADP, the Hill coefficient for ATP hydrolysis was extracted to be 1.0 +/- 0.1, indicating noncooperative behavior of homo-oligomeric Rca assemblies. However, the addition of ADP was shown to introduce positive cooperativity between two or more subunits (Hill coefficient 1.9 +/- 0.2), allowing for regulation via the prevailing ATP/ADP ratio. ADP-mediated activation was not observed, although larger amounts led to competitive product inhibition of hydrolytic activity. The catalytic efficiency increased 8.4-fold upon cooperative binding of a second magnesium ion (Hill coefficient 2.5 +/- 0.5), suggesting at least three conformational states (ATP-bound, ADP-bound, and empty) within assemblies containing an average of about six subunits. The addition of excess Rubisco (24:1, L8S8/Rca6) and crowding agents did not modify catalytic rates. However, high magnesium provided for thermal Rca stabilization. We propose that magnesium mediates the formation of closed hexameric toroids capable of high turnover rates and amenable to allosteric regulation. We suggest that in vivo, the Rca hydrolytic activity is tuned by fluctuating [Mg(2+)] in response to changes in available light. PMID- 26283788 TI - Substrate Specificity and Possible Heterologous Targets of Phytaspase, a Plant Cell Death Protease. AB - Plants lack aspartate-specific cell death proteases homologous to animal caspases. Instead, a subtilisin-like serine-dependent plant protease named phytaspase shown to be involved in the accomplishment of programmed death of plant cells is able to hydrolyze a number of peptide-based caspase substrates. Here, we determined the substrate specificity of rice (Oryza sativa) phytaspase by using the positional scanning substrate combinatorial library approach. Phytaspase was shown to display an absolute specificity of hydrolysis after an aspartic acid residue. The preceding amino acid residues, however, significantly influence the efficiency of hydrolysis. Efficient phytaspase substrates demonstrated a remarkable preference for an aromatic amino acid residue in the P3 position. The deduced optimum phytaspase recognition motif has the sequence IWLD and is strikingly hydrophobic. The established pattern was confirmed through synthesis and kinetic analysis of cleavage of a set of optimized peptide substrates. An amino acid motif similar to the phytaspase cleavage site is shared by the human gastrointestinal peptide hormones gastrin and cholecystokinin. In agreement with the established enzyme specificity, phytaspase was shown to hydrolyze gastrin-1 and cholecystokinin at the predicted sites in vitro, thus destroying the active moieties of the hormones. PMID- 26283787 TI - Membrane Curvature-sensing and Curvature-inducing Activity of Islet Amyloid Polypeptide and Its Implications for Membrane Disruption. AB - Islet amyloid polypeptide (IAPP) is a 37-amino acid amyloid protein intimately associated with pancreatic islet beta-cell dysfunction and death in type II diabetes. In this study, we combine spectroscopic methods and microscopy to investigate alpha-helical IAPP-membrane interactions. Using light scattering and fluorescence microscopy, we observe that larger vesicles become smaller upon treatment with human or rat IAPP. Electron microscopy shows the formation of various highly curved structures such as tubules or smaller vesicles in a membrane-remodeling process, and spectrofluorometric detection of vesicle leakage shows disruption of membrane integrity. This effect is stronger for human IAPP than for the less toxic rat IAPP. From CD spectra in the presence of different sized vesicles, we also uncover the membrane curvature-sensing ability of IAPP and find that it transitions from inducing to sensing membrane curvature when lipid negative charge is decreased. Our in vivo EM images of immunogold-labeled rat IAPP and human IAPP show both forms to localize to mitochondrial cristae, which contain not only locally curved membranes but also phosphatidylethanolamine and cardiolipin, lipids with high spontaneous negative curvature. Disruption of membrane integrity by induction of membrane curvature could apply more broadly to other amyloid proteins and be responsible for membrane damage observed in other amyloid diseases as well. PMID- 26283789 TI - Cyclic diGMP regulates production of sortase substrates of Clostridium difficile and their surface exposure through ZmpI protease-mediated cleavage. AB - In Gram-positive pathogens, surface proteins may be covalently anchored to the bacterial peptidoglycan by sortase, a cysteine transpeptidase enzyme. In contrast to other Gram-positive bacteria, only one single sortase enzyme, SrtB, is conserved between strains of Clostridium difficile. Sortase-mediated peptidase activity has been reported in vitro, and seven potential substrates have been identified. Here, we demonstrate the functionality of sortase in C. difficile. We identify two sortase-anchored proteins, the putative adhesins CD2831 and CD3246, and determine the cell wall anchor structure of CD2831. The C-terminal PPKTG sorting motif of CD2831 is cleaved between the threonine and glycine residues, and the carboxyl group of threonine is amide-linked to the side chain amino group of diaminopimelic acid within the peptidoglycan peptide stem. We show that CD2831 protein levels are elevated in the presence of high intracellular cyclic diGMP (c diGMP) concentrations, in agreement with the control of CD2831 expression by a c diGMP-dependent type II riboswitch. Low c-diGMP levels induce the release of CD2831 and presumably CD3246 from the surface of cells. This regulation is mediated by proteolytic cleavage of CD2831 and CD3246 by the zinc metalloprotease ZmpI, whose expression is controlled by a type I c-diGMP riboswitch. These data reveal a novel regulatory mechanism for expression of two sortase substrates by the secondary messenger c-diGMP, on which surface anchoring is dependent. PMID- 26283790 TI - Glutamate transporter homolog-based model predicts that anion-pi interaction is the mechanism for the voltage-dependent response of prestin. AB - Prestin is the motor protein of cochlear outer hair cells. Its unique capability to perform direct, rapid, and reciprocal electromechanical conversion depends on membrane potential and interaction with intracellular anions. How prestin senses the voltage change and interacts with anions are still unknown. Our three dimensional model of prestin using molecular dynamics simulations predicts that prestin contains eight transmembrane-spanning segments and two helical re-entry loops and that tyrosyl residues are the structural specialization of the molecule for the unique function of prestin. Using site-directed mutagenesis and electrophysiological techniques, we confirmed that residues Tyr(367), Tyr(486), Tyr(501), and Tyr(508) contribute to anion binding, interacting with intracellular anions through novel anion-pi interactions. Such weak interactions, sensitive to voltage and mechanical stimulation, confer prestin with a unique capability to perform electromechanical and mechanoelectric conversions with exquisite sensitivity. This novel mechanism is completely different from all known mechanisms seen in ion channels, transporters, and motor proteins. PMID- 26283791 TI - Disruption of Nucleotide Homeostasis by the Antiproliferative Drug 5 Aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside Monophosphate (AICAR). AB - 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside monophosphate (AICAR) is a natural metabolite with potent anti-proliferative and low energy mimetic properties. At high concentration, AICAR is toxic for yeast and mammalian cells, but the molecular basis of this toxicity is poorly understood. Here, we report the identification of yeast purine salvage pathway mutants that are synthetically lethal with AICAR accumulation. Genetic suppression revealed that this synthetic lethality is in part due to low expression of adenine phosphoribosyl transferase under high AICAR conditions. In addition, metabolite profiling points to the AICAR/NTP balance as crucial for optimal utilization of glucose as a carbon source. Indeed, we found that AICAR toxicity in yeast and human cells is alleviated when glucose is replaced by an alternative carbon source. Together, our metabolic analyses unveil the AICAR/NTP balance as a major factor of AICAR antiproliferative effects. PMID- 26283793 TI - Elias Spiliotis: Septins set it up. PMID- 26283794 TI - The spindle plays both ends. PMID- 26283792 TI - Localization of proteins to the 1,2-propanediol utilization microcompartment by non-native signal sequences is mediated by a common hydrophobic motif. AB - Various bacteria localize metabolic pathways to proteinaceous organelles known as bacterial microcompartments (MCPs), enabling the metabolism of carbon sources to enhance survival and pathogenicity in the gut. There is considerable interest in exploiting bacterial MCPs for metabolic engineering applications, but little is known about the interactions between MCP signal sequences and the protein shells of different MCP systems. We found that the N-terminal sequences from the ethanolamine utilization (Eut) and glycyl radical-generating protein MCPs are able to target reporter proteins to the 1,2-propanediol utilization (Pdu) MCP, and that this localization is mediated by a conserved hydrophobic residue motif. Recapitulation of this motif by the addition of a single amino acid conferred targeting function on an N-terminal sequence from the ethanol utilization MCP system that previously did not act as a Pdu signal sequence. Moreover, the Pdu localized signal sequences competed with native Pdu targeting sequences for encapsulation in the Pdu MCP. Salmonella enterica natively possesses both the Pdu and Eut operons, and our results suggest that Eut proteins might be localized to the Pdu MCP in vivo. We further demonstrate that S. enterica LT2 retained the ability to grow on 1,2-propanediol as the sole carbon source when a Pdu enzyme was replaced with its Eut homolog. Although the relevance of this finding to the native system remains to be explored, we show that the Pdu-localized signal sequences described herein allow control over the ratio of heterologous proteins encapsulated within Pdu MCPs. PMID- 26283795 TI - Paraspeckles: paragons of functional aggregation. AB - Low-complexity proteins undergo phase separation in vitro, forming hydrogels or liquid droplets. Whether these form in vivo, and under what conditions, is still unclear. In this issue, Hennig et al. (2015. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201504117) show that formation of the paraspeckle, a nuclear body that regulates gene expression, requires low-complexity prion-like domains (PLDs) within paraspeckle proteins. The same proteins were shown to form hydrogels, shedding light on the role of "functional aggregation" in nuclear substructure. PMID- 26283797 TI - Mdm1/Snx13 is a novel ER-endolysosomal interorganelle tethering protein. AB - Although endolysosomal trafficking is well defined, how it is regulated and coordinates with cellular metabolism is unclear. To identify genes governing endolysosomal dynamics, we conducted a global fluorescence-based screen to reveal endomembrane effector genes. Screening implicated Phox (PX) domain-containing protein Mdm1 in endomembrane dynamics. Surprisingly, we demonstrate that Mdm1 is a novel interorganelle tethering protein that localizes to endoplasmic reticulum (ER)-vacuole/lysosome membrane contact sites (MCSs). We show that Mdm1 is ER anchored and contacts the vacuole surface in trans via its lipid-binding PX domain. Strikingly, overexpression of Mdm1 induced ER-vacuole hypertethering, underscoring its role as an interorganelle tether. We also show that Mdm1 and its paralogue Ydr179w-a (named Nvj3 in this study) localize to ER-vacuole MCSs independently of established tether Nvj1. Finally, we find that Mdm1 truncations analogous to neurological disease-associated SNX14 alleles fail to tether the ER and vacuole and perturb sphingolipid metabolism. Our work suggests that human Mdm1 homologues may play previously unappreciated roles in interorganelle communication and lipid metabolism. PMID- 26283796 TI - Prion-like domains in RNA binding proteins are essential for building subnuclear paraspeckles. AB - Prion-like domains (PLDs) are low complexity sequences found in RNA binding proteins associated with the neurodegenerative disorder amyotrophic lateral sclerosis. Recently, PLDs have been implicated in mediating gene regulation via liquid-phase transitions that drive ribonucleoprotein granule assembly. In this paper, we report many PLDs in proteins associated with paraspeckles, subnuclear bodies that form around long noncoding RNA. We mapped the interactome network of paraspeckle proteins, finding enrichment of PLDs. We show that one protein, RBM14, connects key paraspeckle subcomplexes via interactions mediated by its PLD. We further show that the RBM14 PLD, as well as the PLD of another essential paraspeckle protein, FUS, is required to rescue paraspeckle formation in cells in which their endogenous counterpart has been knocked down. Similar to FUS, the RBM14 PLD also forms hydrogels with amyloid-like properties. These results suggest a role for PLD-mediated liquid-phase transitions in paraspeckle formation, highlighting this nuclear body as an excellent model system for understanding the perturbation of such processes in neurodegeneration. PMID- 26283798 TI - DNA loops generate intracentromere tension in mitosis. AB - The centromere is the DNA locus that dictates kinetochore formation and is visibly apparent as heterochromatin that bridges sister kinetochores in metaphase. Sister centromeres are compacted and held together by cohesin, condensin, and topoisomerase-mediated entanglements until all sister chromosomes bi-orient along the spindle apparatus. The establishment of tension between sister chromatids is essential for quenching a checkpoint kinase signal generated from kinetochores lacking microtubule attachment or tension. How the centromere chromatin spring is organized and functions as a tensiometer is largely unexplored. We have discovered that centromere chromatin loops generate an extensional/poleward force sufficient to release nucleosomes proximal to the spindle axis. This study describes how the physical consequences of DNA looping directly underlie the biological mechanism for sister centromere separation and the spring-like properties of the centromere in mitosis. PMID- 26283799 TI - TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells. AB - Genome integrity is critically dependent on timely DNA replication and accurate chromosome segregation. Replication stress delays replication into G2/M, which in turn impairs proper chromosome segregation and inflicts DNA damage on the daughter cells. Here we show that TopBP1 forms foci upon mitotic entry. In early mitosis, TopBP1 marks sites of and promotes unscheduled DNA synthesis. Moreover, TopBP1 is required for focus formation of the structure-selective nuclease and scaffold protein SLX4 in mitosis. Persistent TopBP1 foci transition into 53BP1 nuclear bodies (NBs) in G1 and precise temporal depletion of TopBP1 just before mitotic entry induced formation of 53BP1 NBs in the next cell cycle, showing that TopBP1 acts to reduce transmission of DNA damage to G1 daughter cells. Based on these results, we propose that TopBP1 maintains genome integrity in mitosis by controlling chromatin recruitment of SLX4 and by facilitating unscheduled DNA synthesis. PMID- 26283802 TI - Backing up Ayurveda with good science: The modus operandi. PMID- 26283801 TI - FUSED KERNEL-SPLINE SMOOTHING FOR REPEATEDLY MEASURED OUTCOMES IN A GENERALIZED PARTIALLY LINEAR MODEL WITH FUNCTIONAL SINGLE INDEX. AB - We propose a generalized partially linear functional single index risk score model for repeatedly measured outcomes where the index itself is a function of time. We fuse the nonparametric kernel method and regression spline method, and modify the generalized estimating equation to facilitate estimation and inference. We use local smoothing kernel to estimate the unspecified coefficient functions of time, and use B-splines to estimate the unspecified function of the single index component. The covariance structure is taken into account via a working model, which provides valid estimation and inference procedure whether or not it captures the true covariance. The estimation method is applicable to both continuous and discrete outcomes. We derive large sample properties of the estimation procedure and show different convergence rate of each component of the model. The asymptotic properties when the kernel and regression spline methods are combined in a nested fashion has not been studied prior to this work even in the independent data case. PMID- 26283800 TI - Live-cell observation of cytosolic HIV-1 assembly onset reveals RNA-interacting Gag oligomers. AB - Assembly of the Gag polyprotein into new viral particles in infected cells is a crucial step in the retroviral replication cycle. Currently, little is known about the onset of assembly in the cytosol. In this paper, we analyzed the cytosolic HIV-1 Gag fraction in real time in live cells using advanced fluctuation imaging methods and thereby provide detailed insights into the complex relationship between cytosolic Gag mobility, stoichiometry, and interactions. We show that Gag diffuses as a monomer on the subsecond timescale with severely reduced mobility. Reduction of mobility is associated with basic residues in its nucleocapsid (NC) domain, whereas capsid (CA) and matrix (MA) domains do not contribute significantly. Strikingly, another diffusive Gag species was observed on the seconds timescale that oligomerized in a concentration-dependent manner. Both NC- and CA-mediated interactions strongly assist this process. Our results reveal potential nucleation steps of cytosolic Gag fractions before membrane-assisted Gag assembly. PMID- 26283804 TI - Hepatoprotective and antioxidant activity of Karisalai Karpam, a polyherbal Siddha formulation against acetaminophen-induced hepatic damage in rats. AB - BACKGROUND: The usage of Siddha medicine in Tamil Nadu and several parts of Southern India has considerably increased over the past two decades and it is steadily crossing the various geographies owing to its inexpensiveness compared to conventional medicines and has fairly high acceptance rates because of its herbal origin and therefore its nontoxic nature. AIM: This study aims to investigate the anti-hepatotoxic and antioxidant potential of the Karisalai Karpam formulation. MATERIALS AND METHODS: Karisalai Karpam tablet at 50, 100, and 200 mg/kg/day, p.o. doses were administered orally to rats for three consecutive days. Single dose of acetaminophen (3 g/kg, p.o.) was administered on the 3(rd) day. Animals were sacrificed 48 h after the administration of acetaminophen, and their serum bilirubin, different hepatic enzymes and in vivo antioxidant activity were estimated. STATISTICAL ANALYSIS: Data were evaluated using analysis of variance, followed by Tukey tests. A level of P < 0.05 was considered statistically significant. RESULTS: Pretreatment with Karisalai Karpam tablet showed dose-dependent hepatoprotective activity. Karisalai Karpam tablet (200 mg/kg) reduces serum glutamic oxaloacetate transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase and total bilirubin, direct bilirubin by 67.8%, 72.3%, 47.6%, 61.3% and 62.9% respectively compared to disease control group. A significant increase (P < 0.001) in antioxidant enzyme level was observed in Karisalai Karpam treated animals. At higher doses, Karisalai Karpam prevented the depletion of glutathione in liver tissue. CONCLUSION: Results confirmed that Karisalai Karpam tablet could protect the liver against acetaminophen-induced oxidative damage possibly by increasing the antioxidant defence mechanism in rats. PMID- 26283803 TI - Sodhana: An Ayurvedic process for detoxification and modification of therapeutic activities of poisonous medicinal plants. AB - Ayurveda involves the use of drugs obtained from plants, animals, and mineral origin. All the three sources of drugs can be divided under poisonous and nonpoisonous category. There are various crude drugs, which generally possess unwanted impurities and toxic substances, which can lead to harmful health problems. Many authors have reported that not all medicinal plants are safe to use since they can bear many toxic and harmful phytoconstituents in them. Sodhana (detoxification/purification) is the process, which involves the conversion of any poisonous drug into beneficial, nonpoisonous/nontoxic ones. Vatsanabha (Aconitum species), Semecarpus anacardium, Strychnos nux-vomica, Acorus calamus, Abrus precatorius etc., are some of the interesting examples of toxic plants, which are still used in the Indian system of medicine. Aconite, bhilawanols, strychnine, beta-asarone, abrin are some of the toxic components present in these plants and are relatively toxic in nature. Sodhana process involves the purification as well as reduction in the levels of toxic principles which sometimes results in an enhanced therapeutic efficacy. The present review is designed to extensively discuss and understand the scientific basis of the alternative use of toxic plants as a medicine after their purification process. PMID- 26283805 TI - Formation and validation of questionnaire to assess Jatharagni. AB - BACKGROUND: Jatharagni (metabolic fire) is of the prime importance in the maintenance of health as well as causation of diseases. Food which is consumed by the person shares the major responsibility for being healthy or manifestation of diseases. The relation between food and health is mediated by Jatharagni (the metabolic agent in Ayurveda). There are four different states of Jatharagni viz, Mandagni (mild or weak state of metabolic fire), Visamagni (irregular state of metabolic fire), Tiksnagni (sharp or intense state of metabolic fire), and Samagni (Normal state of metabolic fire). Samagni (Normal state of metabolic fire) is said to be the normal State and maintains the health of an individual. All the other states are considered as abnormal. OBJECTIVES: To frame and validate a Questionnaire to assess the state of Jatharagni. MATERIALS AND METHODS: A qualitative research that involved interview method and cluster sampling method. A total of 500 volunteers of either gender in two groups viz., apparently healthy and unhealthy were assessed for their Jatharagni. Questionnaire was framed with 64 items. A total of 14 questions under Visamagni (irregular state of metabolic fire), 13 under Tikshnagni, 13 under Mandagni and 24 questions under Samagni were framed. The questionnaire was in optional format with 5 item likert's scale pattern and the validation was done by Cronbach's Alpha for internal consistency. RESULT: The internal consistency of the questionnaire using Cronbach's Alpha was 0.916. The internal consistency of Visamagni domain was 0.909; Teekshnagni domain was 0.873; Mandagni domain was 0.894; and Samagni domain was 0.876. CONCLUSION: The internal consistency of the questionnaire was 0.909 which is indicative of the excellent internal consistency of questionnaire. The lacuna of tool to assess state of Jatharagni in Ayurveda is filled by this questionnaire. PMID- 26283806 TI - Evaluation of prakrti and quality-of-life in patients with irritable bowel syndrome. AB - OBJECTIVE: To evaluate the prakrti of irritable bowel syndrome (IBS) patients and its association with IBS subtypes and quality-of-life (QOL). METHODOLOGY: IBS patients with the consistent subtype in the last 6 months were recruited. Prakrti assessment with a 24-item questionnaire was performed and depending on the scores the patients were categorized into vata predominant, pitta predominant, and kapha predominant prakrti. QOL was assessed with prevalidated disease-specific 34-item questionnaire scored on a 0-100 scale. RESULTS: Of 50 IBS patients enrolled, with mean age of 43.5 +/- 12.8 years, and male: female as 43:7, 22 patients were of vata and pitta predominant prakrti each while six patients had kapha predominant prakrti. IBS-C was diagnosed in 24 patients, IBS-D in 21, and IBS-M in five patients. In vata predominant group, IBS-C was found in 13 patients, IBS-D in 8, and IBS-M in 1. In pitta predominant group, IBS-D was found in 13, IBS-C in 6, and IBS-M in 3. In kapha predominant group, IBS-C was found in 5 patients and IBS M in 1. The median QOL in IBS-C group was 48.897, IBS-D was 38.97, and IBS-M was 66.911. The median QOL score 52.205, 42.27, and 55.51 in vata, pitta, and kapha predominant group, respectively. CONCLUSION: Majority of the vata predominant patients had developed IBS-C, pitta predominant patients had developed IBS-D. QOL was better in pitta predominant individuals of all IBS-disease subtypes. With this, we find that prakrti examination in IBS helps in detecting the proneness of developing an IBS subtype and predicting their QOL accordingly. PMID- 26283807 TI - Efficacy of herbomineral compounds and pathya (Ayurvedic dietary regime and physical exercise) in the management of Yakrt Roga (Non-alcoholic fatty liver disease). AB - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) also called as hepatic steatosis is a manifestation of excessive triglyceride accumulation in the liver. NAFLD has been described by histological features ranging from simple fatty liver, nonalcoholic steatohepatitis, progressive fibrosis, and liver failure. OBJECTIVE: The objective was to evaluate the effect of herbomineral drugs and pathya (Ayurvedic dietary regime and physical exercise) in the management of NAFLD. MATERIALS AND METHODS: It is a randomized, retrospective, open-ended study. A total of 32 patients presenting with raised alanine transaminase (>1.5 times normal levels) combined with sonological evidence of fatty liver in the absence of any other detectable cause of liver disease were included in the study. The recruited patients were randomly divided into two groups - The patients in Group-A (n = 21) were given a combination of herbomineral drugs Arogyavardhini vati and Triphala Guggulu along with prescription of pathya (Ayurvedic dietary regime and physical exercise); the patients in Group-B (n = 11) were advised only pathya. RESULTS: Group-A (combined therapy group) showed statistically significant improvement in clinical symptoms, biochemical parameters-liver function test, lipid profile, fasting blood sugar, and body mass index (P < 0.001) in comparison to Group-B (pathya group). CONCLUSION: Combination of herbomineral drugs along with pathya has shown promising results toward the effective management of this metabolic disorder. PMID- 26283808 TI - Pharmacognostical evaluation of aerial parts of Graptophyllum pictum (L.) Griff. (Syn: Justicia picta Linn.): A well-known folklore medicinal plant. AB - OBJECTIVE: Graptophyllum pictum (L.) Griff. (Family-Acanthaceae) occupies a key role in traditional system of medicine. Since an extensive literature survey did not provide any information about studies on its standardization. Therefore, we designed the current study to establish the quality control parameters of G. pictum aerial parts. MATERIALS AND METHODS: The investigation included determination of various standardization parameters such as macroscopic and microscopic studies, physicochemical parameters as well as phytochemical analysis of the crude drug. RESULTS: The microscopy study of aerial parts revealed that stem shows typical dicotyledonous characters with prismatic crystals of calcium oxalate in the cortical region and dorsiventral leaf. Physicochemical constants such as moisture content, ash values, fluorescence analysis, and extractive values were established. Preliminary phytochemical analysis confirmed the presence of alkaloids, flavonoids, saponins, tannins, etc. CONCLUSION: The present study suggests establishing the parameters for pharmacopoeial standardization of G. pictum. PMID- 26283810 TI - A Conversation with Dr. (Med.) Valdis Pirags, Head of Internal Medicine Department, Paula Stradina Kliniska Universitates Slimnica, Riga, Latvia. PMID- 26283811 TI - The First International Research Seminar on Ayurveda (2014), Birstein, Germany. PMID- 26283809 TI - Ayurvedic approach in the management of spinal cord injury: A case study. AB - Spinal cord injury (SCI) is associated with consequences such as full loss of spinal movements, incontinence of bladder functions, bed sores, etc. There is no satisfactory treatment available in biomedicine with only limited treatments only for enhancement of spinal cord function. These treatments have many limitations. Ayurvedic drugs and Pancakarma procedures have been in use to treat such conditions since a long time. We present a case of SCI with lesion at C4 level which was treated for 2 months with an Ayurvedic combined intervention. The combined treatment plan involved Ayurvedic oral medications (Brhadvatacintamani rasa - 125 mg, Ardhanagavatari rasa - 125 mg, Dasamula kvatha - 40 ml, Asvagandhacurna [powder of Withania somnifera DUNAL] - 3 g, Amrta [Tinospora cordifolia WILLD] - 500 mg, Muktasukti pisti - 500 mg and Trayodasanga guggulu - 500 mg) twice daily. Combined procedures involved such as salisastika pindasvedana (sudation with medicated cooked bolus of rice) every day for 2 months and Matra basti (enema) for first 15 days with Asvagandha oil. From 16(th) day, Mustadi yapana basti (MYB, enema with medicated milk) was given for 16 days. After an interval of 7 days, MYB was further repeated for next 16 days. Substantial clinical improvement was reported after 2 months of the Ayurvedic treatment in existing neurological deficits and in quality of life. PMID- 26283812 TI - Coping with Job Loss and Reemployment: A Two-Wave Study. AB - Using a national sample, this study investigated the effects of unemployed workers' coping resources and coping strategy use on reemployment after a three month period. Based on previous research, it was expected that (1) three types of coping resources (self-esteem, social support, and financial resources) would be positively related to problem-focused coping with job loss, (2) coping resources would be negatively related to emotion-focused coping with job loss, (3) problem focused coping would be positively related to reemployment, (4) problem-focused coping would be more strongly related to reemployment than emotion-focused coping, and (5) coping strategies would mediate the relationship between the availability of coping resources and obtaining reemployment. Results provided support for the direct effects of coping resources (self-esteem, social support, and, to some extent, financial resources) on coping strategies, and a direct effect of problem-focused coping on reemployment 3 months later. Self-esteem and social support were each indirectly related to subsequent employment status, mediated by problem-focused coping. In other words, individuals with higher levels of self-esteem and social support were not only more likely to engage in problem-focused coping, but having a higher level of self-esteem and social support was also associated with a higher likelihood of being reemployed three months later. Findings are pertinent for the design of more effective interventions that mitigate adverse effects of unemployment and facilitate a successful return to the workforce. PMID- 26283813 TI - Advancement in biochemical diagnostics and regenerative medicine leading to integration of dentistry into 360 degrees health program. PMID- 26283814 TI - Knowledge and attitude of dental surgeons in India toward ocular complications of intra-oral local anesthesia. AB - BACKGROUND: Ocular disturbances such as blurring of vision, mydriasis, palpebral ptosis, diplopia, ptosis, enophthalmos, miosis, and blindness (temporary or permanent) are rare complications due to intra-oral local anesthesia. Currently, the guidelines to dentists on preventing and caring for such ocular problems are lacking. Hence, we evaluated the knowledge and attitudes of dentists toward ocular complications of intra-oral anesthesia as a means to assess the need for such guidelines. MATERIALS AND METHODS: A cross-sectional prospective survey targeting dentists was conducted using a self-administered questionnaire. Totally 500 standardized self-administered questionnaires were sent out by E-mail to practicing dentists or academicians. In total, 390 replies were received, and the data were analyzed. RESULTS: About 39% of graduates and 14% postgraduate dentists knew about ocular complications. Journals were the leading source of information among both graduates and postgraduate dentists. 8.3% graduates and 17.6% postgraduate dentists encountered ocular complications. Interestingly most of the graduates and postgraduates responded that ocular complications are underreported in the literature. 90.5% graduates and 84.3% postgraduates are in the opinion that more research should be carried on ocular complications. 98.3% postgraduates and 97.3% graduates favored the prevention of ocular complications. CONCLUSION: The dentist's knowledge about ocular complications due to intra-oral anesthesia in our study group is not adequate and needs improvement. Although the awareness and practice of taking preventive measures are satisfactory, there is a need for specific guidelines to dentists in identifying and clinically managing ocular complications of intra-oral anesthesia. PMID- 26283815 TI - Osteostimulatory effect of bone grafts on fibroblast cultures. AB - OBJECTIVE: We analyzed the morphological changes and alkaline phosphatase (ALP) level in fibroblast, which is indicative of their functional ability when cultured in three different commercially available graft materials with osseoconductive property. MATERIALS AND METHODS: Fibroblasts obtained from fifth passage were seeded within three different bone substitutes (bovine hydroxyapatite [HA] [Osseo-graft((r))], beta-tricalciumphosphate [RTR((r))], bovine HA [Bio-oss((r))]) and incubated under standard cell culture conditions. 10 samples in each group were evaluated for cell morphology and alkaline phosphates activity using scanning electron microscopy and spectrophotometric analysis on the 7(th) day of culture. RESULTS: Fibroblast cultured with RTR((r)) showed changes in morphology and increase in ALP activity when compared to fibroblast cultured with Osseo-graft((r)) and Bio-oss((r)). CONCLUSION: Alkaline phosphatase activity was observed in fibroblasts when cultured with three types of commercially available bone grafts. ALP activity was highest when cultured with beta-tricalcium phosphate graft material indicating its better bone regenerating capacity of this graft material. PMID- 26283816 TI - Dermatoglyphic patterns and salivary pH in subjects with and without dental caries: A cross-sectional study. AB - BACKGROUND: Dermatoglyphic patterns, which are regularly used in judicial and legal investigations, can be valuable in the diagnosis of many diseases associated with genetic disorders. Dental caries although of infectious origin, may have a genetic predisposition. Hence, we evaluated the correlation between dental caries and dermatoglyphic patterns among subjects with and without dental caries and evaluated its association with environmental factors such as salivary pH. MATERIALS AND METHODS: Totally, 76 female students within the age group of 18 23 years were clinically examined, and their decayed, missing, filled teeth (DMFT) score and oral hygiene index-simplified were recorded. Based on their DMFT score, they were divided into following three groups; group I (n = 16, DMFT score = 0), group II (n = 30, DMFT score <5), and group III (n = 30, DMFT score >=5). Their fingerprint patterns and salivary pH were recorded and analyzed using descriptive statistics. RESULTS: Dermatoglyphic pattern distribution in caries free group showed more ulnar loops than high caries group (group III) while high caries group showed more whorl patterns. Presence of whorl with double loop, whorl within a loop was associated with high DMFT score. The total finger ridge count was lower in caries group. The mean salivary pH was higher in caries-free group than high caries group. Thus, we conclude that dermatoglyphic patterns may be potential diagnostic tool for detecting patients prone to develop dental caries. PMID- 26283817 TI - Oral Candidal and Streptococcal carriage in Down syndrome patients. AB - AIM: We aimed to evaluate the prevalence of Candida and Streptococci species in the oral cavity of Down syndrome patients. MATERIALS AND METHODS: 50 children/adolescents with Down syndrome with a karyotype of 47 XX, 21+ (female) and 47 XY, 21+ (male), and 50 normal children/adolescents were included in our study. Oral swab/saliva was used to culture and identify Candida and Streptococci species based on gram and periodic acid schiff staining. RESULTS: Of the 50 study group samples, which were cultured, 37 (74%) showed growth of Candida colonies, whereas in the 50 control samples only 18 (36%) were positive for Candida growth. In 4 Sabouraud's dextrose agar culture slopes of the study group, more than one morphological type of colonies were observed. 23 out of 50 samples in our study group had Streptococcus viridans colonies. In the 23 samples positive for Streptococci 16 had many streptococcal colonies, and 7 had few streptococcal colonies in the primary culture. 32 out of 50 samples from the control group had S. viridans colonies. In these 32 samples positive for Streptococci, 29 had predominantly streptococcal colonies while 3 had few streptococcal colonies in the primary culture. CONCLUSION: The oral cavity is an environment heavily colonized by microorganisms, however, the Down syndrome patients run a greater risk of having opportunistic infections especially from Candida species. Hence to improve the quality of life of an individual with Down syndrome, it is necessary to diagnose and treat these infections by more frequent oral microbial assessment. PMID- 26283818 TI - Dimensional and morphological analysis of various rugae patterns in Kerala (South India) sample population: A cross-sectional study. AB - BACKGROUND: Analysis of palatal rugae patterns, which are similar to fingerprints, is one of the techniques used in forensic sciences for human identification. As palatal rugae patterns are genetically determined, they can also be used in population differentiation and gender determination. Hence, we aimed to record the distribution of the predominant rugae pattern in Kerala population. MATERIALS AND METHODS: A total of 100 maxillary study models (40 males and 60 females) recorded from Kerala population within the age group of 17 25 years were analyzed. The dental casts were examined for the interpretation of the total number, length, shape, location and unification of rugae. Chi-square test and unpaired t-test were employed for statistical analysis. RESULT: The total number of rugae was significantly (P < 0.001) greater in females than males. Regarding the shape, wavy pattern predominated in both males and females, followed by curve, straight, divergent, convergent and circular pattern. Circular pattern was more in males than females. The rugae patterns were located more in between mesial aspect of first premolar to mesial aspect of second premolar. CONCLUSION: The palatal rugae and their features of an individual may be considered as a reliable guide for identification purpose, provided antemortem casts are available. Nevertheless, gender differentiation is evident in terms of number and shape of rugae. PMID- 26283819 TI - Predentin thickness analysis in developing and developed permanent teeth. AB - BACKGROUND: Predentin, the unmineralized organic matrix is important in maintaining the integrity of dentin. It is usually thick where active dentinogenesis occurs. A wide variation in its thickness is reported. Hence, we determined the variation in predentin thickness at various sites of different age groups. MATERIALS AND METHODS: 60 freshly extracted teeth (maxillary and mandibular first premolars) were divided into three groups with 20 teeth in each as, Group 1 - teeth with incomplete root formation (age <16 years), Group 2 - teeth with complete root formation (aged between 16 and 30 years), Group 3 - teeth of patients aged above 30 years. The teeth were fixed, decalcified and sections of 6 MU thickness were obtained, and stained with hematoxylin and eosin. The distance between the odontoblastic cell layers of the pulp to the border line of the dentin was considered for the measurement of the predentin thickness. A total of nine sites were considered for each specimen. RESULTS: The present study revealed varied mean predentin thickness at all nine sites in all three age groups. Maximum and minimum thickness was observed at the apex and pulp floor respectively in all three groups. There was a statistical significant difference in predentin thickness between groups 1 and 3 and 2 and 3. CONCLUSION: The predentin thickness in the first group gradually increased toward the growing end near the apex, while it was relatively constant in the second group and increased overall thickness at all the sites in the third group. A notable finding was a linear increase with age in width of the predentin and the thickness vary as a function of odontoblastic activity during different stages of tooth development. PMID- 26283821 TI - Vestibular stimulation: A simple but effective intervention in diabetes care. AB - Despite the complexities of the relationship between vestibular stimulation and endocrine disorders being well known, research efforts to understand these complexities are lacking. Interestingly vestibular stimulation may potentially prevent/delay development/progression of diabetes. Here we review the science behind this concept and highlight the need for necessary translational research in this area. Current evidence supports the use of vestibular stimulation not only as a potential intervention to prevent or delay the development of diabetes mellitus in at-risk population, but also to use it as supplementary therapy for diabetic patients management. We urge clinicians to recommend vestibular stimulation by simple means like swing as a goal in maintaining a healthy lifestyle. PMID- 26283820 TI - Recent advances in the diagnosis and treatment of childhood tuberculosis. AB - Despite over 2.3 million (26% of global burden) cases of tuberculosis (TB) in India the accurate diagnosis of childhood TB remains a major challenge. Children with TB usually have paucibacillary disease and contribute little to disease transmission within the community. Consequently the treatment of children with TB is often not considered a priority by TB control programmes. Adequate and timely assessment of TB infection in childhood could diminish epidemiological burden as underdiagnosed pediatric patients can eventually evolve in to an active state and have the potential to disseminate the etiological agent Mycobacterium tuberculosis, notably increasing this worldwide public health problem. In this review we discuss the most important recent advances in the diagnosis of childhood TB: (1) Symptom-based approaches, (2) novel immune-based approaches, including in vitro interferon-gamma IGRA release assays IGRA tests; and (3) bacteriological and molecular methods that are more rapid and/or less expensive than conventional culture techniques for TB diagnosis and/or drug-resistance testing. Recent advances have improved our ability to diagnose latent infection and active TB in children, nevertheless establishing a diagnosis of either latent infection or active disease in HIV-infected children remains a major challenge. PMID- 26283822 TI - Knowledge, attitude, and practices related to cervical cancer among adult women: A hospital-based cross-sectional study. AB - BACKGROUND: Cervical cancer is the most common cancer among Indian women of reproductive age. Unfortunately, despite the evidence of methods for prevention, most of the women remain unscreened. The reported barriers to screening include unawareness of risk factors, symptoms and prevention; stigma and misconceptions about gynecological diseases and lack of national cervical cancer screening guidelines and policies. This study attempts to assess the knowledge, attitude, and practices related to cervical cancer and its screening among women of reproductive age (15-45 years). MATERIALS AND METHODS: A facility-based cross sectional study was done on 400 females of reproductive age who presented to out patient-department of All India Institute of Medical Sciences Bhopal. Structured questionnaire consisting 20 knowledge items and 7-items for attitude and history of pap smear for practices were administered by one of the investigators after informed consent. Data were entered and analyzed using Epi-Info version 7. Qualitative variables were summarized as counts and percentages while quantitative variables as mean and standard deviation. Predictors of better knowledge, attitude, and practices were identified by binary logistic regression analysis. RESULTS: A total of 442 women were approached for interview of which 400 responded of which two-third (65.5%) had heard of cervical cancer. At least one symptom and one risk factor were known to 35.25% and 39.75% participants. Only 34.5% participants had heard, and 9.5% actually underwent screening test, however, 76.25% of the participants expressed a favorable attitude for screening. Binary logistic regression analysis revealed that education age and income were independent predictors of better knowledge. Education level influences attitude toward screening and actual practice depends on age, income, and marital status. This study shows that despite the fact that women had suboptimal level of knowledge regarding cervical cancer, their attitude is favorable for screening. However, uptake is low in actual practice. Strategic communication targeting eligible women may increase the uptake of screening. PMID- 26283823 TI - Influence of lifestyle patterns on perceptions of obesity and overweight among expatriates in Abha city of Kingdom of Saudi Arabia. AB - BACKGROUND: We evaluated the influence of lifestyle patterns such as watching TV, working with computer and idle sitting time on perceptions of obesity and beliefs about overweight are associated with obesity and overweight amongst Expatriates in Abha. MATERIALS AND METHODS: The method used in this study was a cross sectional survey with a self-administered paper-based questionnaire. The survey collected information on lifestyle choices and the risk factors that contribute to obesity. In addition, height and weight were measured. RESULTS: Greater number of our study subjects spent over 2 h/day without any physical activity, specifically accounting for over 2 h/day each in viewing TV, computer, and spending idle time. This increased lack of physical activities was significantly associated with overweight. While the overweight subjects were aware of very wide options for treating their condition, a significant number believed in self effort in managing their diet and exercise regimen as the best efforts to reduce their overweight. Interestingly very few overweight subjects considered medication or surgery as a potential therapeutic option and 75% of the overweight subjects considered overweight to be of no or only slight concern on wellbeing. CONCLUSIONS: Overweight and obesity among expatriates within Saudi Arabia poses an important public health problem. The lack of awareness about the potential impact of obesity on health and optimal treatment options is a serious concern, which needs to be addressed by appropriate public health programs at national level. PMID- 26283824 TI - Toxic effects of Mn2O3 nanoparticles on rat testis and sex hormone. AB - BACKGROUND AND OBJECTIVE: The safety of Mn2O3 nanoparticles (which are extensively used in industries) on male reproductive system is not known. Hence, we investigated the effects of Mn2O3 nanoparticles on male reproductive system. MATERIALS AND METHODS: A total of 40 Wistar adult male rats were randomly assigned to four groups of 10 rats each. Three groups received Mn2O3 solution in concentrations of 100, 200, and 400 ppm orally for 14 days; the control group received equal volume of saline solution. Blood samples and testicles were collected for analysis. RESULTS: Significant reduction in luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, spermatogonial cells, primary spermatocyte, spermatid and Leydig cell was observed in the Mn2O3 nanoparticles treated groups compared with controls. CONCLUSION: Mn2O3 nanoparticles significantly reduce FSH, LH, and testosterone levels resulting in a significant reduction in testicular cytology. PMID- 26283825 TI - Effects of fluconazole, chlorhexidine gluconate, and silver-zinc zeolite on flexural strength of heat-cured polymethyl methacrylate resin. AB - AIM: We evaluated the effect of incorporating Fluconazole, Chlorhexidine Gluconate, and Silver-Zinc Zeolite as bioactive materials (10% of mass) on the flexural strength of commercially available heat-cured polymethyl methacrylate (PMMA; Travelon). MATERIALS AND METHODS: The following four groups were compared; Group 1: Control group with pure PMMA, Group 2: Antibacterial drug group with chlorhexidine gluconate in powder form + PMMA, Group 3: Antifungal drug group with fluconazole in powder form + PMMA, Group 4: Antimicrobial agent group with silver zinc zeolite in powder form + PMMA. After processing, the specimens were subjected for flexural strength testing using three-point bending test in a universal testing machine. RESULTS: A significant (P < 0.0001) decrease in flexural strength following incorporation of Fluconazole, Chlorhexidine Gluconate, and Silver-Zinc Zeolite to heat polymerized acrylic resin was observed when compared with the control group. The decrease in mean flexural strength was minimal in the fluconazole group. CONCLUSION: Although the addition of a bioactive material to PMMA acrylic is desirable, it is not practical as it reduces flexural strength of the acrylic base. PMID- 26283826 TI - Estimation of alkaline phosphatase in the gingival crevicular fluid during orthodontic tooth movement in premolar extraction cases to predict therapeutic progression. AB - OBJECTIVES: The objective was to estimate the level of alkaline phosphatase (ALP) in gingival crevicular fluid (GCF) during en-masse retraction stage of orthodontic tooth movement. MATERIALS AND METHODS: 10 patients in the age group of 15-20 years participated in this study. GCF was sampled from the distal surface of the canine and mesial surface of the second premolar on day 0, 1, 7, 14, 21, and 28 postorthodontic treatment. RESULTS: A marked fall in the level of ALP was evident following force application. A progressive decreasing trend in ALP activity on both distal aspect of canine and mesial aspect of the second premolar was observed. The fall in ALP was more on distal aspect canine when compared to the mesial aspect of the second premolar. CONCLUSIONS: Measure of ALP activity in GCF could be an indicator of the biochemical and cellular alterations in bone turnover and hence rate the amount of tooth movement following orthodontic force application. PMID- 26283827 TI - Lipid profile but not highly sensitive C-reactive protein helps distinguish prehypertensives from normal subjects. AB - BACKGROUND: Early identification of the prehypertensive state can greatly improve the disease risk management. Although increased levels of highly sensitive C reactive protein (hsCRP) and dyslipidemia is reported among patients with hypertension, the correlation of these parameters among prehypertensives in not known. Hence, the present study was designed to compare the levels of serum hsCRP and lipid profile among prehypertensives and normal subjects and correlate it with blood pressure (BP) levels. MATERIALS AND METHODS: Anthropometric measurements and BP were recorded in 40 prehypertensive and 40 normal subjects. Subjects were assigned to a group based on their BP as per Joint National Committee 7 criteria. Serum hsCRP and lipid profile were measured and correlated with BP levels. RESULTS: Serum hsCRP showed no significant difference between the two groups. There was no significant correlation of BP with hsCRP in both the groups. Total cholesterol (TC) and low-density lipoprotein (LDL) were significantly increased in prehypertensives as compared to normal subjects. There was no significant association between BP and lipid parameters in prehypertensives. CONCLUSIONS: Significant increase of TC and LDL but not hsCRP was evident among prehypertensives as compared to normal subjects. PMID- 26283828 TI - Protective effects of fish oil, allopurinol, and verapamil on hepatic ischemia reperfusion injury in rats. AB - BACKGROUND: The major aim of this work was to study the protective effects of fish oil (FO), allopurinol, and verapamil on hepatic ischemia-reperfusion (IR) induced injury in experimental rats. MATERIALS AND METHODS: Sixty male Wistar albino rats were randomly assigned to six groups of 10 rats each. Group 1 served as a negative control. Group 2 served as hepatic IR control injury. Groups 3, 4, 5, and 6 received N-acetylcysteine (standard), FO, allopurinol, and verapamil, respectively, for 3 consecutive days prior to ischemia. All animals were fasted for 12 h, anesthetized and underwent midline laparotomy. The portal triads were clamped by mini-artery clamp for 30 min followed by reperfusion for 30 min. Blood samples were withdrawn for estimation of serum alanine transaminase (ALT) and aspartate transaminase (AST) activities as well as hepatic thiobarbituric acid reactive substances, reduced glutathione, myeloperoxidase, and total nitrate/nitrite levels, in addition to histopathological examination. RESULTS: Fish oil, allopurinol, and verapamil reduced hepatic IR injury as evidenced by significant reduction in serum ALT and AST enzyme activities. FO and verapamil markedly reduced oxidative stress as compared to control IR injury. Levels of inflammatory biomarkers in liver were also reduced after treatment with FO, allopurinol, or verapamil. In accordance, a marked improvement of histopathological findings was observed with all of the three treatments. CONCLUSION: The findings of this study prove the benefits of FO, allopurinol, and verapamil on hepatic IR-induced liver injury and are promising for further clinical trials. PMID- 26283830 TI - Isolation, screening, and molecular characterization of plant growth promoting rhizobacteria isolates of Azotobacter and Trichoderma and their beneficial activities. AB - OBJECTIVES: The present study was conducted for isolation, screening, and identification of Azotobacter and Trichoderma from different soil samples. METHODS: A total of 10 isolates of Azotobacter and Trichoderma were isolated from rhizospheric soils. The test isolates were biochemically characterized and screened in in-vitro conditions for their plant growth promoting properties. DNA polymorphism of isolates was studied using randomly amplified polymorphic DNA analysis. RESULTS: A total of 41 bands were scored, out of which 35 bands were found to be 85.59% polymorphic in Azotobacter and in Trichoderma among total 37 bands scored of which 29 were found to be 78.37% polymorphic. The influence of isolated plant growth promoting rhizobacteria (PGPR) strains on plant growth was studied using different parameters such as height of the plant, number of leaves, and number of branches, and bio-control activity was studied. CONCLUSION: The present results concluded that the multiple beneficial activities of PGPR traits increase the plant growth and bio-control activity. PMID- 26283829 TI - Fast foods and physical inactivity are risk factors for obesity and hypertension among adolescent school children in east district of Sikkim, India. AB - BACKGROUND: Obesity and hypertension among school children have a huge impact on public health. Hence, we estimated the prevalence and sociodemographic correlates of childhood obesity and elevated blood pressure (BP) among adolescent schoolchildren (11-19 years) in urban areas of Gangtok, Sikkim, India. MATERIALS AND METHODS: A population based cross-sectional study was conducted on 979 school children, during November 1, 2009 - April 30, 2010 in Gangtok, East Sikkim India. Anthropometric measurements and BP were recorded among the study population. Obesity and hypertension prevalent among adolescent school children and their correlates were analyzed. RESULTS AND CONCLUSION: Prevalence of obesity, overweight, and hypertension was 2.04%, 14.5% and 5.62%, respectively. The average fast food intake, screen time and limited outdoor activities were significantly associated with obesity. Increase in abdominal height positively correlated with increase in body mass index and body fat; however waist - hip ratio was not a reliable index. The burden of overweight/obesity as well as hypertension with all its associated risk was found to high among our study population, which necessitates framing of policies and actions at national level to address the risk associated with these noncommunicable diseases. PMID- 26283831 TI - The antiplaque efficacy of propolis-based herbal toothpaste: A crossover clinical study. AB - BACKGROUND: In recent years, herbal products have been suggested as an economic, safe and probably effective alternative for prevention and control of various oral diseases. But still there are some products which need to be evaluated. Of lately, Propolis is one such product. To assess and compare the efficacy of herbal dentifrice containing Propolis with Miswak and Colgate total toothpastes in controlling plaque formation. MATERIALS AND METHODS: A double blind, randomized, crossover study design was conducted among thirty healthy dental students. After oral prophylaxis all subjects were given a washout product for one week period. Subjects were then made to brush with (washout product) for 1 minute followed by 1 minute brushing with assigned test product. The baseline MGMPI plaque scores were recorded. Subjects were then refrained from oral hygiene for 24 hours, and were recalled to be re-disclosed and re-measured for plaque formation. This procedure was repeated according to crossover design after a washout period of (2 week). Statistical tests used were Krukalwallis and Wilcoxon sign rank test. RESULTS: There was a significant difference in 24 hour score between the test products evaluated. When the change from baseline to 24 hours was analyzed, the test product Propolis resulted in a consistently and significantly (p < 0.05) lower MGMPI mean scores than the Colgate Total and Miswak toothpastes. CONCLUSION: Propolis was found to be safe and effective in reducing plaque accumulation when compared to Miswak and Colgate total toothpaste. PMID- 26283832 TI - Epidemiology and symptoms of red eyes in patients from Northern Iran. AB - AIM: We aimed to determine the epidemiology and symptoms of red eyes in patients from Northern Iran. MATERIALS AND METHODS: A descriptive study was planned involving 840 patients referred to the eye clinic of Bu-Ali Sina hospital in Sari, Iran, with the chief complaint of eye redness. RESULTS: Of 840 patients, 525 were men (62.5%) and 315 were women (37.5%). Most of the patients were over 39 years of age. 55.7 percentage of them lived in cities and 44% were from villages. The most common eye symptoms with eye redness were: Eye abrasion (57%), tears in eyes (49%) and swollen eye lid (30%). Red eyes without any symptoms in eyes were diagnosed as runny nose (4.2%) and headaches (3.4%). 11.9% and 19.6% of the patients had a previous history of red eye and had visited doctors for red eyes respectively. CONCLUSIONS: Red eyes are more common in men than women. Introducing dangerous causes of red eyes in the future can help to health care professional to on time diagnosis of red eyes related problems. PMID- 26283833 TI - Nutrition and health status of school children in urban area of Ahmedabad, India: Comparison with Indian Council of Medical Research and body mass index standards. AB - BACKGROUND: Identifying the commonly prevailing health and nutritional disorders in school going children is essential to initiate appropriate public health measures. MATERIALS AND METHODS: A cross-sectional prospective study was designed to conduct a detail physical health assessment of children studying in class 1-8 (age- 5-13 years) of 31 schools of Ahmedabad city, India between December 2011 and February 2012. Under the school health program of state government, medical history, height, weight and general physical examination findings, including dental and ophthalmic examination were recorded by qualified medical practitioners. Children with abnormal results were further investigated and treated by the subject experts. RESULT: Total 28,256 children were screened (boys 15,087 and girls-13,169). Mean weight and height of the children were 27.04 kg and 128.81 cm, respectively. Analysis of nutritional status of the cohort population as compared to body mass index standards revealed that 8319 (29.44%) children were underweight while only 221 (0.78%) children were either overweight or obese. The subgroup analysis of basic nutrition indices in children revealed prevalence of significant malnutrition (based on Indian Council of Medical Research standards) in children below 10 years of age. Commonly prevailing health disorders included worm infestation (42%), upper respiratory tract infection (36.39%), anemia (30.99%) dental caries (25.19%) and refractory errors (10.2%). CONCLUSIONS: Malnutrition and related health disorders are commonly prevailing childhood diseases in the urban community and can effectively be addressed by appropriate public health program. PMID- 26283834 TI - Effect of intraoperative infusion of low-dose ketamine on management of postoperative analgesia. AB - BACKGROUND: Use of opioids for perioperative analgesia is associated with sedation, respiratory depression and postoperative nausea and vomiting. N-methyl D-aspartate receptor antagonist such as ketamine has both analgesic and antihyperalgesic properties. We studied the effect of intraoperative infusion of low-dose ketamine on postoperative analgesia and its management with opioids. MATERIALS AND METHODS: A total of 80 patients scheduled for open cholecystectomy under general anesthesia were randomly allocated into two equal groups in a randomized double-blinded way. The general anesthetic technique was standardized in both groups. Group K patients (n = 40) received bolus of ketamine 0.2 mg/kg intravenously followed by an infusion of 0.1 mg/kg/h before skin incision, which was continued up to the end of surgery. Similar volume of saline was infused in Group C (n = 40). The pain score at different intervals and cumulative morphine consumption over 24 h was observed. Secondary outcomes such as hemodynamic parameters, patient satisfaction score and incidences of side effects were also recorded. RESULTS: Intraoperative infusion of low-dose ketamine resulted in effective analgesia in first 6 h of the postoperative period, which was evident from reduced pain scores and reduced opioid requirements (P = 0.001). The incidence of side effects and patient satisfaction were similar in both groups. CONCLUSION: Intraoperative low-dose ketamine infusion provides good postoperative analgesia while reducing need of opioid analgesics, which must be considered for better management of postoperative analgesia. PMID- 26283835 TI - Phenotypic detection of extended spectrum beta-lactamase and Amp-C beta-lactamase producing clinical isolates in a Tertiary Care Hospital: A preliminary study. AB - BACKGROUND: Production of beta-lactamase enzymes by Gram-negative bacteria is the most common mechanism to acquire drug resistance to beta-lactam antibiotics. Limitations in detecting extended spectrum beta-lactamases (ESBL) and Amp-C beta lactamases have contributed to the uncontrolled spread of bacterial resistance and are of significant clinical concern. MATERIALS AND METHODS: A total of 148 samples was selected on the basis of resistance against third-generation cephalosporin for screening ESBLs and Amp-C beta-lactamases production. These multidrug-resistant strains were phenotypically screened for ESBL production by phenotypic confirmatory disc diffusion test and double disc synergy test. Modified three-dimensional method was used for Amp-C beta-lactamases detection. RESULT: Among the 148 isolates, 82 (55.40%) were ESBL producers, and 115 (77.70%) were Amp-C beta-lactamases producers. Co-existence of ESBL and Amp-C was observed in 70 (47.29%) isolates. Escherichia coli was the most common ESBL and Amp-C beta lactamase producer. All ESBL producers were highly resistant to ciprofloxacin (83.10%), cotrimoxazole (95.27%), and gentamicin (89.18%). However, these bacterial strains were sensitive to imipenem 146 (98.64%) and piperacillin/tazobactam 143 (96.62%). CONCLUSION: Our study showed that ESBL producing organisms were not only resistant to cephalosporins but also to other group of drugs and also that multiple mechanisms play a role in drug resistance among Gram-negative bacteria. PMID- 26283836 TI - Utility of magnetic resonance imaging in the differential diagnosis of tubercular and pyogenic spondylodiscitis. AB - AIM: We evaluated the potential of magnetic resonance imaging (MRI) in the diagnosis of spinal infections and specifically its accuracy in differentiating tubercular and pyogenic spondylodiscitis. MATERIALS AND METHODS: Totally, 50 patients referred for MRI scans with the clinical diagnosis of spinal infections were included in our study. The patients were classified as tubercular (TS), pyogenic (PS), and indeterminate spondylodiscitis on the basis of imaging findings and were correlated with the final diagnosis made by histopathology/cytology/culture/biochemistry or with successful therapeutic outcome. Imaging findings were subsequently analyzed for differentiating tubercular and pyogenic spondylodiscitis using the Chi-square test. RESULTS: The most common pattern of spinal infection was spondylodiscitis (78% incidence rate) with epidural extension (86%) and cord compression (64%) being most common complications observed. Imaging (postcontrast study) and final diagnosis correlated in 93.7% tubercular (sensitivity of 75% and specificity of 90%) and 75% pyogenic (sensitivity of 90% and specificity of 83.3%) spondylodiscitis. The patients with tubercular spondylitis had a significantly (P < 0.05) higher incidence of following MRI findings: A well-defined paraspinal abnormal signal (80% in TS vs. 40% in PS), a thin and smooth abscess wall (84.2% in TS vs. 10% in PS), presence of intraosseous abscess (35% in TS vs. 0% in PS), focal and heterogenous enhancement of the vertebral body (75% in TS vs. 20% in PS), vertebral destruction more than or equal to grade 3 (71.8% in TS vs. 0% in PS), loss of cortical definition (75% in TS vs. 20% in PS), and spinal deformity (50% in TS vs. 5% in PS). CONCLUSION: Contrast-enhanced images improve the sensitivity and specificity of detection and differentiation of tubercular and PS. PMID- 26283837 TI - Antibiotic resistance pattern of Enterococci isolates from nosocomial infections in a tertiary care hospital in Eastern India. AB - BACKGROUND: Resistance to commonly used antibiotics by Enterococci causing nosocomial infections is of concern, which necessitates judicious, responsible and evidence-based use of antibiotics. The present study was conducted to review the prevalence and identify therapeutic options for nosocomial Enterococcal infections in our tertiary care hospital. MATERIALS AND METHODS: Isolates identified by morphological and biochemical characteristics were tested for antibiotic susceptibility using Kirby-Bauer method. RESULT: 153 of 2096 culture positive clinical samples comprised of 101 urine, 30 wound swab/pus, 13 blood and 09 high vaginal swab isolates were identified as Enterococcus faecalis (90.85%), Enterococcus faecium (8.50%) and Enterococcus gallinarum (0.65%). Enterococci accounted for 8.45%, 4.53%, 4.23%, 4.43% of urinary, wound swab or pus, blood, high vaginal swab isolates respectively, causing 7.3% of all nosocomial infections. Significant number of Enterococci isolated from nosocomial urinary tract infection (66.01%) and wound infections (19.6%) were multidrug resistant (MDR). Although all isolates were sensitive to vancomycin and linezolid, resistance to erythromycin (71.24%) and ciprofloxacin (49.67%) was frequently observed. High-level gentamicin resistance was observed in 43.88%, and 61.53% of E. faecalis and E. faecium isolates respectively. Minimal inhibitory concentration of vancomycin of all the isolates were <=1 MUg/ml. 7% of the Enterococcal isolates were MDR strains and vancomycin or linezolid were the only effective antibiotics. CONCLUSION: A combination of vancomycin and/or linezolid were effective against Enterococci causing nosocomial infections in our tertiary care facility, nevertheless continuous and frequent surveillance for resistance patterns are necessary for judicious and evidence based use of antibiotics. PMID- 26283838 TI - A prospective study assessing clinicians attitude and knowledge on radiation exposure to patients during radiological investigations. AB - BACKGROUND: Exposure to radiation during radiological investigations is of health concern, which referring physicians should rationalize. Hence, we assessed the clinician's awareness and concern of radiation exposure to patients, in relation to their referral practice. MATERIALS AND METHODS: A prospective study was conducted involving specialists from Punjab (India), who were handed a standard set of questionnaire concerning knowledge of radiation hazards and doses from imaging procedures, consideration of radiation dose and age when referring, referrals not likely to affect treatment, and use of referral guidelines were included. Of the 150 medical doctors given the questionnaire, 106 returned it. RESULTS: Majority of the clinicians underestimated radiation doses, while a few overestimated it. Almost half of the clinicians (55.5%) favored to select the rationale of asking about previous radiological examinations as clinical need only, which was surprising. Rates of referrals unlikely to affect treatment were more (66%) than reported rates in previous studies. Worryingly, only 30.1% of the clinicians had knowledge of referral guidelines and alarmingly only 10.5% had made use of it. CONCLUSIONS: Our study although in a small population size identifies inadequate knowledge on radiation and its guidelines among referral physicians, which warrants the immediate need for training programs to bridge this knowledge gap. PMID- 26283839 TI - Anti-thyroid peroxidase antibody positivity during early pregnancy is associated with pregnancy complications and maternal morbidity in later life. AB - AIMS: We assessed the impact of detecting anti-thyroid peroxidase antibodies (anti-TPO-Ab) in the first trimester of pregnancy on pregnancy outcomes and maternal thyroid function during the postpartum period. MATERIALS AND METHODS: In a prospective study consisting 400 pregnant women (8-12 weeks pregnant) were screened for their thyroid profile and followed-up to 12 weeks postpartum. Patients with abnormal thyroid function at 12 weeks postpartum were further followed-up with repeated assessment of thyroid stimulating hormone (TSH) and serum-free thyroxine-4 levels at 8 weeks interval up to 12 months postpartum. RESULTS: 11.5% of the subjects were positive for anti-TPO-Ab who had mean TSH level of 2.31 MUIU/ml, which was significantly (P- 0.0001) higher than pregnant women negative for anti-TPO-Ab (1.73 MUIU/ml). Increased incidence of miscarriage was observed in anti-TPO positive mothers when compared to antibody negative mothers. Postpartum thyroid dysfunction developed in 4.7% cases at 12 weeks, among them antibody positivity was observed in 81.25% of subjects. In 18.75% mothers positive for anti-TPO-Ab, the thyroid dysfunction persisted up to 12 months postpartum. CONCLUSIONS: Thyroid antibodies detected in early pregnancy seems to be predicting pregnancy complications and later maternal thyroid disease related morbidity. PMID- 26283840 TI - Comparing Ksharasutra (Ayurvedic Seton) and open fistulotomy in the management of fistula-in-ano. AB - BACKGROUND: Most commonly practiced surgical "lay open" technique to treat fistula-in-ano (a common anorectal pathology) has high rate of recurrence and anal incontinence. Alternatively, a nonsurgical cost efficient treatment with Ksharasutra (cotton Seton coated with Ayurvedic medicines) has minimal complications. In our study, we have tried to compare these two techniques. MATERIALS AND METHODS: A prospective randomized control study was designed involving patients referred to the Department of General Surgery in RG Kar Medical College, Kolkata, India, from January 2010 to September 2011. RESULTS: Among 50 patients, 26 were in Ksharasutra and 24 were in fistulotomy group. 86% patients were male and 54% of the patients were in the fourth decade. About 74% fistulas are inter-sphincteric and 26% were of trans-sphincteric variety. Severe postoperative pain was more (7.7% vs. 25%) in fistulotomy group, while wound discharge was more associated with Ksharasutra group (15.3% vs. 8.3%). Wound scarring, bleeding, and infection rate were similar in both groups. Ksharasutra group took more time to heal (mean: 53 vs. 35.7 days, P = 0.002) despite reduced disruption to their routine work (2.7 vs. 15.5 days work off, P <0.001). Interestingly, pain experienced was less in Ksharasutra group, there was no open wound in contrast to fistulotomy and it was significantly cost effective (Rupees 166 vs. 464). CONCLUSION: Treatment of fistula-in-ano with Ksharasutra is a simple with low complications and minimal cost. PMID- 26283841 TI - Evaluating the cost effectiveness of national program for control of blindness in Jorhat district, India. AB - BACKGROUND: We evaluated the cost of different components of the national program for control of blindness (NPCB) and assess the cost effectiveness of this program. MATERIALS AND METHODS: An observational study was conducted in Jorhat District of Assam, India from July 2009 to June 2010 for assessing the cost effectiveness of the NPCB. Four broad categories of cost inputs, that is, capital costs, recurrent costs, prime/variable costs, and fixed costs were considered. The cost incurred by the provider was taken as the actual cost of delivery of different component of services to the patients, which was calculated from the costs of labor, material, and capital costs using the time utilization pattern recommended by WHO. RESULT: The District Blindness Control Society, Jorhat had spent 58.93% of total expense on fixed heads of which 65.86% had been spent for cataract surgery. The medical care cost was found to be Indian rupee (INR) 425 for intracapsular cataract extraction (ICCE), INR 675 for extracapsular cataract extraction + intraocular lens (ECCE + IOL) and INR 225 for refractive error correction. The patient-wise provider cost was estimated to be INR 519 for ICCE, INR 769 for ECCE + IOL implantation and INR 319 for spectacle correction of refractive error. CONCLUSION: National program for control of blindness is a cost effective means of controlling and treating blindness. PMID- 26283842 TI - Immunomodulatory potential of shatavarins produced from Asparagus racemosus tissue cultures. AB - Medicinal properties of Asparagus racemosus (vernacular name: Shatavari) are attributed to its steroidal saponins called shatavarins. This plant is facing the threat of being endangered due to several developmental, seasonal constrains and malpractices involved in its collection and storage. To support its conservation, a tissue culture protocol is standardized which produces 20 fold higher levels of shatavarin. Here we evaluate the bioactivity and immunomodulatory potential of in vitro produced shatavarins from cell cultures of AR using human peripheral blood lymphocytes. In vitro produced shatavarin stimulated immune cell proliferation and IgG secretion in a dose dependent manner. It stimulated interleukin (IL)-12 production and inhibited production of IL-6. It also had strong modulatory effects on Th1/Th2 cytokine profile, indicating its potential application for immunotherapies where Th1/Th2 balance is envisaged. Our study demonstrating the bioactivity of tissue cultured AR extracts supports further in vivo evaluation of its immunomodulatory efficacy. PMID- 26283844 TI - Detection of antidiabetic activity by crude paratoid gland secretions from common Indian toad (bufomelano stictus). AB - BACKGROUND: Amphibians have provided a remarkable array of biological active compounds, which are secreted from socalled granular skin glands which serve to protect the amphibians from predators due to its noxious effects on buccal tissue and at least in the case of some peptides, to protect from bacterial (or) protozoan infections. Given the respiratory and antimicrobial functions of amphibian skin, it is likely that some of the novel molecules found in amphibian granular gland secretions might be of use in the treatment of skin and respiratory infections. Secretions from common Indian toad (Bufo melanostictus) a member of Bufonidae family has the history of medicinal use however the anti diabetic activity is not reported. The present study is aimed to determine whether paratoid gland extract have any influence on the diabetes and the pharmacokinetics and pharmacodynamics of glimepiride (GLM) in normal and diabetic rats. MATERIALS AND METHODS: An aqueous and methanolic extracts of paratoid glandular secretions were prepared, air dried and used to determine the antidiabetic activity in rats. The blood sampling was done at preset time intervals between 0, 0.5, 1, 2, 4, 6, 8 and 12 h, using heparinized capillaries. The blood glucose levels are estimated by glucose oxidase-peroxidase method, and reversed-phase high-performance liquid chromatography is used to determine the pharmacokinetic parameters of GLM using glibenclamide as an internal standard. RESULTS: Both the aqueous and methanolic extracts produced better glycemic control in diabetic rats, and methanolic extract is better than the aqueous extract. Serum concentrations of GLM increased at 2(nd) h, and the percentage glucose reduction is maximal at the 4(th) h with both aqueous and methanolic extracts of paratoid secretions of common Indian toad. CONCLUSIONS: Paratoid gland secretions of the common Indian toad is antidiabetic, in addition it has beneficial effects in combination with GLM. Further, it requires the systematic structure elucidation of the compounds and pharmacokinetic studies to explore the beneficial effects. PMID- 26283845 TI - Case reports on atypical presentation of Plasmodium falciparum malaria in pediatric patients. AB - Variable atypical symptoms are commonly observed in malaria caused by Plasmodium falciparum especially in endemic tropical nations such as India. Nystagmus is observed following involvement of the cerebellum especially during the postrecovery phase. While psychotic features such as severe agitation, hallucination, paranoia may be the early symptoms of falciparum malaria among pediatric patients, urticaria with or without fever can be the initial manifestation of the disease. As the morbidity and mortality of severe malaria are very high in India, these atypical presentations should be considered during diagnosis. We believe our report on atypical cases of falciparum malaria will sensitize doctors and health personnel about rare presentations in children and help in early diagnosis and management to reduce the severity and death toll due to the disease. PMID- 26283843 TI - Protective effects of ginger and marshmallow extracts on indomethacin-induced peptic ulcer in rats. AB - BACKGROUND: Gastric ulcer is one of the most serious diseases. Most classic treatment lines produce adverse drug reactions. Therefore, this study aimed to investigate the protective effects of two natural extracts, namely ginger and marshmallow extracts, on indomethacin-induced gastric ulcer in rats. MATERIALS AND METHODS: Animals were divided into five groups; a normal control group, an ulcer control group, and three treatment groups receiving famotidine (20 mg/kg), ginger (100 mg/kg), and marshmallow (100 mg/kg). Treatments were given orally on a daily basis for 14 days prior to a single intra-peritoneal administration of indomethacin (20 mg/kg). RESULTS: Indomethacin administration resulted in significant ulcerogenic effect evidenced by significant elevations in ulcer number, ulcer index, and blood superoxide dismutase activity accompanied by significant decreases in gastric mucosal nitric oxide and glutathione levels. In addition, elevations in gastric mucosal lipid peroxides and histamine content were observed. Alternatively, pretreatment with famotidine, ginger or marshmallow significantly corrected macroscopic and biochemical findings, supported microscopically by results of histopathological study. CONCLUSION: These results demonstrate that administration of either ginger or marshmallow extract could protect against indomethacin-induced peptic ulcer in rats presumably via their antioxidant properties and inhibition of histamine release. PMID- 26283846 TI - Giant malignant peripheral nerve sheath tumor with cauda equina syndrome and subarachnoid hemorrhage: Complications in a case of type 1 neurofibromatosis. AB - Type 1 neurofibromatosis (NF1), which mainly involves ectodermal tissue arising from the neural crest, can increase the risk of developing malignant peripheral nerve sheath tumors (MPNSTs), soft tissue sarcomas and subarachnoid hemorrhage. We describe a patient with neurofibromatosis type 1 who developed soft tissue sarcoma, MPNST, and subarachnoid hemorrhage. A 22-year-old male reported right focal seizures consequence to severe headache. He had a weakness in both legs, could walk only with the support of a stick for the last 3 months and suffered from constipation and intermittent urinary retention for the past 1 week. The patient had a history of swelling in the back of left thigh for which surgical resection was done 6 months back. Cutaneous examination revealed multiple nodules of varying sizes all over the body, along with many cafe-au-lait spots and Lisch nodule in iris. Patient had weakness in bilateral hip abduction, extension, knee flexion, extension and ankle dorsiflexion and plantiflexion. Bilateral ankle reflexes were absent while other deep tendon reflexes were sub-optimal. A noncontrast computed tomography brain indicated subarachnoid hemorrhage in left perisylvian region. Ultrasound of left thigh showed a hypoechoic solid lesion in the posterior aspect of left thigh in muscle plane. Histopathology of the lesion following resection showed features suggestive of a low-grade pleomorphic rhabdomyosarcoma. Histology of cutaneous nodules was consistent with neurofibroma. Magnetic resonance imaging of the lumbosacral spine demonstrated a tumor arising from cauda equina. Histopathological examination of the tumor suggested high-grade MPNST. Unfortunately, the patient's MPNST was inoperable, and he received palliative radiotherapy for local control of the disease. The care of a patient with neurofibromatosis requires a comprehensive multisystem evaluation. MPNST occurs in 8-13% patients with neurofibromatosis. Early diagnosis and surgical resection are key to prolong survival. Though rare, rhabdomyosarcoma can occur with a higher frequency in NF1, necessitating through clinical investigation. Subarachnoid hemorrhage can occur due to aneurismal rupture or vascular friability in NF1 patients. PMID- 26283847 TI - Rare case of multiple aggressive vertebral hemangiomas. AB - A case of a 42-year-old man with back pain associated with left radiculopathy and infiltrative mass involving the T12 and L5 vertebrae is described. Magnetic resonance imaging (MRI) and computed tomography indicated aggressive hemangiomas involving the T12 and L5 vertebrae. Three-year follow-up by imaging indicated minimally increased aggressiveness of the L5 lesion without any significant change in appearance of the T12 lesion thus, confirming the initial diagnosis of multiple aggressive vertebral hemangiomas. PMID- 26283849 TI - Esthetic and biologic mode of reattaching incisor fracture fragment utilizing glass fiber post. AB - Trauma to the anterior teeth affects the esthetic and psychological well-being of the patient. Advancement in the adhesive dentistry has facilitated the restoration of the coronal tooth fractures by minimally invasive procedures when the original tooth fragment is available. Reattachment of fractured fragment offers immediate treatment with improved preponderant aesthetics and restoration of function. Here, we describe a case of complicated fracture of the maxillary left immature permanent central incisor, which was treated endodontically followed by esthetic reattachment of the fractured fragment using the glass fiber post. Functional demands and esthetic considerations of the patient were fully met with this biologic mode of fragment reattachment. PMID- 26283848 TI - The radiculous' premolars: Case reports of a maxillary and mandibular premolar with three canals. AB - Successful root canal therapy requires an accurate diagnosis and management of complex root canal morphology. Although the occurrence of three root canals in maxillary and mandibular premolars is very rare, the clinician must be able to identify it clinically and radiographically to make the necessary changes in his shaping and obturation techniques. We present the endodontic management of a maxillary first premolar with three separate roots and canals, which was diagnosed with the aberrant anatomy only after the access preparation. Then, a mandibular premolar with three root canals and fused roots, which were diagnosed radiographically, is presented. The necessary modifications of the routine clinical steps and the application of dental operating microscope for successful management of the complex anatomy, with emphasis on access modifications and radiographic interpretations are also explained. Teeth with extra roots and/or canals pose a challenge in clinical management. Identifying them early is necessary to facilitate appropriate modifications in treatment protocol, armamentarium to be used and plan optimal number of treatment sittings. PMID- 26283850 TI - Prosthetic management of hemimandibulectomy patient with guiding plane and twin occlusion prosthesis. AB - Mandibular deviation is multifactorial defect and its severity is based on the extent of osseous and soft tissue involvement, degree of tongue impaired, the loss of sensory and motor innervations, the type of wound closure, the presence of remaining natural teeth and finally the first initiation of prosthetic treatment. We describe a case of prosthetic management of a maxillary partially edentulous patient with hemimandibulectomy who reported after 4 years of postsurgical cancer therapy. A simple maxillary guided hollow inclined plane with twin occlusion acrylic prosthesis was fabricated as a functional training device to correct mandibular deviation, restore maxillomandibular relation and occlusal approximation. The patient was able to functionally achieve good maxillomandibular occlusal approximation with guidance therapy combined with physiotherapy in 2 weeks. A 6 months follow-up revealed patient satisfactory appreciation by understanding the limitations of overall prosthetic rehabilitation. PMID- 26283851 TI - A rare case of femoral herniation of female internal genitalia. AB - We report a rare case with herniation of the uterus, fallopian tube, and ovary in a femoral hernia. A female patient was admitted with complain of the painful lump in the left groin. Clinical examination indicated strangulated femoral hernia, which necessitated an emergency surgery. During surgical procedure, the uterine tube, left fallopian tube and left ovary, were observed as the contents of the hernia. The contents were reduced back into the pelvic cavity, and the hernia was repaired. The patient made good recovery postsurgery. PMID- 26283852 TI - Mucormycosis causing maxillary osteomyelitis. AB - Mucormycosis is an opportunistic fungal infection, more commonly observed in immunocompromised patients. The mode of infection is via the inhalation route and infection begins initially in the nose and paranasal sinuses with subsequent invasion into the vascular tissue, eventually leading to thrombosis and necrosis of nearby hard and soft tissues. Here, we report a case of chronic osteomyelitis of the maxillary bone with fungal infection (mucormycosis) and extensive tissue necrosis in an uncontrolled diabetes mellitus patient. PMID- 26283853 TI - Oral Kaposi's sarcoma: Sole presentation in HIV seropositive patient. AB - Acquired immunodeficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS) occurs with increased frequency in all HIV transmission groups and at a particularly high rate among homosexual men. It usually presents initially as violaceous cutaneous lesions, but oral mucosa, lymph nodes and visceral organs may be affected, sometimes without skin involvement. KS in a 20-year-old HIV seropositive patient with oral involvement as the sole presentation of the disease is presented herewith; thus contributing a new AIDS-related KS case reported in Indian Literature. PMID- 26283854 TI - Monostotic fibrous dysplasia with Raynaud's phenomenon. AB - Fibrous dysplasia (FD) is a benign bone disorder characterized by alteration in bone morphology. Monostotic FD is the commonest variant and affects the craniofacial bones. Raynaud's phenomenon is recurrent vasospasm of the fingers and toes due to cold exposure. The disease is usually idiopathic or secondary to connective tissue disorders. Raynaud's phenomenon is not described previously with FD. We recently encountered two interesting patients of craniofacial monostotic FD with Raynaud's phenomenon and report the same in this report. PMID- 26283855 TI - Management of chronic suppurative osteomyelitis in a patient with pycnodysostosis by intra-lesional antibiotic therapy. AB - Pycnodysostosis is a rare sclerosing bone disorder characterized by short stature, brachycephaly, short/stubby fingers, open cranial sutures/fontanelle, and diffuse osteosclerosis, where multiple fractures of long bones and osteomyelitis of the jaw are common complications. We present a rare case of pycnodysostosis with chronic suppurative osteomyelitis of the mandible in a 36 year-old woman; which was nonsurgically managed by a conservative approach involving a novel protocol referred to as intra-lesional antibiotic therapy. PMID- 26283856 TI - Karyotype, Pedigree and cone-beam computerized tomography analysis of a case of nonsyndromic pandental anomalies. AB - This case report presented a karyotype and pedigree analysis of a case with unusual combination of dental anomalies: Generalized short roots, talon cusps, dens invagination, low alveolar bone heights, very prominent cusp of carabelli and protostylid on first permanent molars, taurodontism of second permanent molars, rotated, missing and impacted teeth. None of the anomalies alone are rare. However, until date, nonsyndromic pandental anomalies that are affecting entire dentition with detailed karyotype, pedigree and cone-beam computerized tomography analysis have not been reported. The occurrence of these anomalies is probably incidental as the conditions are etiologically unrelated. PMID- 26283857 TI - An unusual initial presentation of hepatocellular carcinoma as a sellar mass. AB - Sellar masses are frequently adenomatous pituitary tumors. Metastatic disease is unusual, often mimicking the presentations of adenomas. Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy but unusual to have a pituitary metastasis (PM). A 65-year-old man presented with headache, diplopia, ptosis, decreased vision in the right eye and unintentional weight loss of 32lbs. Preliminary out-patient work-up revealed a mass in the pituitary region. Cranial imaging showed 3.1 cm * 3.2 cm * 4.4 cm lesion. Abdominal imaging (computed tomography and magnetic resonance imaging) demonstrated a lobulated, nodular and heterogeneous right lobe of the liver. Trans-sphenoidal resection of the sellar mass favored metastatic HCC on histology. Liver biopsy confirmed HCC. We recommend maintaining an increased clinical suspicion upon evaluation of nonclassical clinical and radiological presentations of suspected PM/malignancy; as well as pursuing additional investigations in all early cases. PMID- 26283858 TI - Breast abscess in a case of duct atresia caused by CO2-auxotrophic small colony variants of Staphylococcus aureus: Case report and review of literature. AB - Small colony variants (SCV) are persistent, intracellular morphotypes of Staphylococcus aureus causing indolent, subclinical infections. They are usually auxotrophic for Thymidine, menadione or carbon dioxide. Diagnosis is often misleading due to small colony type, delayed coagulase activity and lack of hemolysis. We hereby describe a case of CO2-auxotrophic SCV of S. aureus causing left breast abscess in a young female with duct atresia of breast, detected by increased colony size in CO2 rich environment. SCVs can often be missed and have to be identified and treated properly. PMID- 26283859 TI - Enterobius vermicularis infestation masquerading as cervical carcinoma: A cytological diagnosis. AB - Although prevalence of Enterobius vermicularis (EV) infestation in Intestines ranges from 35% to 70%, its prevalence in female genital tract is not known despite several incidental findings. Acute inflammatory cells in the background of cervical Pap smear indicate infestation and should not be neglected as contamination. A 40-year-woman presented with white vaginal discharge persistent for past 1 year. Local examination showed hypertrophied cervix with eversion of both lips and hard consistency of the anterior lip of cervix. A clinical diagnosis of cervical carcinoma was made. However, cervical Pap smear indicated EV eggs in an inflammatory background, treatment to which resulted in completely recovery. PMID- 26283860 TI - Development of hyperplastic polyps following argon plasma coagulation of gastric antral vascular ectasia. AB - The etiology of gastric antral vascular ectasia (GAVE) syndrome or gastric hyperplastic polyps (HPs) is not fully understood. We report a case of gastric HP arising in a patient treated with argon plasma coagulation (APC) for GAVE syndrome. Despite unclear etiologic progression, this and previously reported cases suggest a temporal relationship between the treatment of GAVE and HP. A 68 year-old male with a history of coronary artery disease, congestive heart failure and diabetes type II who initially presented with symptomatic anemia 2 weeks after starting aspirin and clopidogrel therapy. Diagnostic esophagogastroduodenoscopy (EGD) demonstrated diffuse GAVE. He was treated with 5 APC treatments, at 6-week intervals, over a 30 weeks period. 16 months after the initial APC treatment, an EGD performed secondary to persistent anemia demonstrated innumerable, large, bleeding polyps in the gastric antrum. Biopsy performed at that time confirmed hyperplastic gastric polyps. It has been proposed that HPs are regenerative lesions that arise at sites of severe mucosal injury. Our patient's treatment of GAVE with APC created significant mucosal injury, resulting in HP. Technique and genetic factors may have promoted hyperplastic changes during the regeneration of mucosa, at sites previously treated with APC. This case highlights the potential progression of GAVE to HP in a patient with persistent anemia after APC therapy. PMID- 26283861 TI - Disruption of eyelid and cornea morphogenesis by epithelial beta-catenin gain-of function. AB - PURPOSE: To examine the developmental pathobiology of the eyelid and the cornea caused by epithelial beta-catenin gain-of-function (gof) during mouse embryogenesis. METHODS: Compound mutant mice (Ctnnb1(GOFOSE) , gof of beta catenin in the epidermis and the ocular surface epithelium) were generated by time-mating keratin 5-promoter-Cre recombinase (Krt5-Cre) and Ctnnb1(fE3/WT) (floxed exon 3 of Ctnnb1) mice. Eyes obtained from wild-type (WT) and mutant embryos at various gestation stages until E18.5 were examined with histology and immunohistochemistry. The ultrastructure of the ocular tissues of the E18.5 embryos was also examined. RESULTS: Expression of the gof-beta-catenin mutant protein in the epidermis severely impaired eyelid morphogenesis at E15.5, E17.5, and E18.5. The mutant stroma exhibited impaired keratocyte differentiation with accelerated cell proliferation and reduction in the accumulation of collagen type I. The mutant embryos also showed hyperproliferative nodules in the ocular surface epithelia with anomaly of cornea-type epithelial differentiation and the absence of the epithelial basement membrane. CONCLUSIONS: Expression of the gof beta-catenin mutant protein in basal epithelial cells disrupts eyelid and cornea morphogenesis during mouse embryonic development due to the perturbation of cell proliferation and differentiation of the epithelium and the neural crest-derived mesenchyme. PMID- 26283862 TI - Hesperetin prevents selenite-induced cataract in rats. AB - PURPOSE: This study investigated the ability of hesperetin, a natural flavonoid, to prevent selenite-induced cataracts in a rat model. METHODS: Animals were divided into four treatment groups: G1 (control group), G2 (hesperetin-treated group), G3 (selenite-induced cataract group), and G4 (hesperetin-treated selenite cataract group). Animals in the G1 and G3 groups were injected with vehicle alone, while those in the G2 and G4 groups received a subcutaneous injection of hesperetin (0.4 MUg/g bodyweight on days 0, 1, and 2, corresponding to P13, P14, and P15). Sodium selenite (20 MUmol/g bodyweight given 4 h after the hesperetin injection on day 0) was administered to rats in the G3 and G4 groups to induce cataract formation. Lenses were observed with slit-lamp microscopy, and filensin degradation and the decreased glutathione (GSH) and ascorbic acid levels in the lens were measured on day 6. RESULTS: Lenses in the G3 group showed mature central opacity, while some lenses in the G4 group lacked central opacity and had lower-grade cataracts. All lenses in the G1 and G2 groups were transparent. Expression of the 94 kDa and 50 kDa forms of filensin was significantly decreased in the lenses in the G3 group compared with those in the G1 and G2 groups. Interestingly, these forms of filensin rescued the rat lenses in the G4 group. In the G3 group lenses, the GSH and ascorbic acid levels were lower than in the control group but were normalized in the G4 group lenses. CONCLUSIONS: The results suggest that hesperetin can prevent selenite-induced cataract formation. PMID- 26283863 TI - Variable phenotypic expressivity in inbred retinal degeneration mouse lines: A comparative study of C3H/HeOu and FVB/N rd1 mice. AB - PURPOSE: Recent advances in optogenetics and gene therapy have led to promising new treatment strategies for blindness caused by retinal photoreceptor loss. Preclinical studies often rely on the retinal degeneration 1 (rd1 or Pde6b(rd1)) retinitis pigmentosa (RP) mouse model. The rd1 founder mutation is present in more than 100 actively used mouse lines. Since secondary genetic traits are well known to modify the phenotypic progression of photoreceptor degeneration in animal models and human patients with RP, negligence of the genetic background in the rd1 mouse model is unwarranted. Moreover, the success of various potential therapies, including optogenetic gene therapy and prosthetic implants, depends on the progress of retinal degeneration, which might differ between rd1 mice. To examine the prospect of phenotypic expressivity in the rd1 mouse model, we compared the progress of retinal degeneration in two common rd1 lines, C3H/HeOu and FVB/N. METHODS: We followed retinal degeneration over 24 weeks in FVB/N, C3H/HeOu, and congenic Pde6b(+) seeing mouse lines, using a range of experimental techniques including extracellular recordings from retinal ganglion cells, PCR quantification of cone opsin and Pde6b transcripts, in vivo flash electroretinogram (ERG), and behavioral optokinetic reflex (OKR) recordings. RESULTS: We demonstrated a substantial difference in the speed of retinal degeneration and accompanying loss of visual function between the two rd1 lines. Photoreceptor degeneration and loss of vision were faster with an earlier onset in the FVB/N mice compared to C3H/HeOu mice, whereas the performance of the Pde6b(+) mice did not differ significantly in any of the tests. By postnatal week 4, the FVB/N mice expressed significantly less cone opsin and Pde6b mRNA and had neither ERG nor OKR responses. At 12 weeks of age, the retinal ganglion cells of the FVB/N mice had lost all light responses. In contrast, 4-week-old C3H/HeOu mice still had ERG and OKR responses, and we still recorded light responses from C3H/HeOu retinal ganglion cells until the age of 24 weeks. These results show that genetic background plays an important role in the rd1 mouse pathology. CONCLUSIONS: Analogous to human RP, the mouse genetic background strongly influences the rd1 phenotype. Thus, different rd1 mouse lines may follow different timelines of retinal degeneration, making exact knowledge of genetic background imperative in all studies that use rd1 models. PMID- 26283865 TI - UV-blocking spectacle lens protects against UV-induced decline of visual performance. AB - PURPOSE: Excessive exposure to sunlight may be a risk factor for ocular diseases and reduced visual performance. This study was designed to examine the ability of an ultraviolet (UV)-blocking spectacle lens to prevent visual acuity decline and ocular surface disorders in a mouse model of UVB-induced photokeratitis. METHODS: Mice were divided into 4 groups (10 mice per group): (1) a blank control group (no exposure to UV radiation), (2) a UVB/no lens group (mice exposed to UVB rays, but without lens protection), (3) a UVB/UV400 group (mice exposed to UVB rays and protected using the CR-39TM spectacle lens [UV400 coating]), and (4) a UVB/photochromic group (mice exposed to UVB rays and protected using the CR-39TM spectacle lens [photochromic coating]). We investigated UVB-induced changes in visual acuity and in corneal smoothness, opacity, and lissamine green staining. We also evaluated the correlation between visual acuity decline and changes to the corneal surface parameters. Tissue sections were prepared and stained immunohistochemically to evaluate the structural integrity of the cornea and conjunctiva. RESULTS: In blank controls, the cornea remained undamaged, whereas in UVB-exposed mice, the corneal surface was disrupted; this disruption significantly correlated with a concomitant decline in visual acuity. Both the UVB/UV400 and UVB/photochromic groups had sharper visual acuity and a healthier corneal surface than the UVB/no lens group. Eyes in both protected groups also showed better corneal and conjunctival structural integrity than unprotected eyes. Furthermore, there were fewer apoptotic cells and less polymorphonuclear leukocyte infiltration in corneas protected by the spectacle lenses. CONCLUSIONS: The model established herein reliably determines the protective effect of UV blocking ophthalmic biomaterials, because the in vivo protection against UV induced ocular damage and visual acuity decline was easily defined. PMID- 26283864 TI - Characterization of ex vivo cultured limbal, conjunctival, and oral mucosal cells: A comparative study with implications in transplantation medicine. AB - PURPOSE: Limbal epithelial stem cell deficiency is caused by exposure of the cornea to thermal, chemical, or radiation burns or by diseases (aniridia and Stevens-Johnson syndrome). Autologous cell transplantation is a widely used therapeutic modality for restoring the corneal surface in such pathological conditions. Ex vivo cultured limbal, conjunctival, and oral biopsies have been widely used to reconstruct the corneal surface with variable outcomes. Culture characterization of the ex vivo cultured cells would provide insight and clues into the underlying signaling mechanisms that would aid in determining the probable transplantation outcome. Comparison of the vital proteins and genes among the three ex vivo cultured tissues has implications in clinical practice. To address this issue, we characterized and compared the proliferative and differentiated properties of ex vivo cultured limbal, conjunctival, and oral biopsies used for cell-based therapy for corneal surface restoration. METHODS: Limbal, conjunctival, and oral biopsies were collected with informed patient consent. Explant cultures were established on the denuded human amniotic membrane with corneal lineage differentiation medium. The day 14 cultures were characterized for epithelial and corneal lineage-specific markers using reverse transcription (RT)-PCR for cytokeratin 3, 4, 12, 13, 15, connexin 43, vimentin, p63alpha, and ABCG2 markers. mRNA expression was estimated in day 14 cultures with real-time quantitative real time (qRT)-PCR for pluripotency markers (OCT4, SOX2, NANOG), putative corneal stem cell markers (ABCG2 and p63alpha), proliferation markers (cyclin d1, Ki-67, PCNA, and CDC20), apoptotic markers (BCL2, BAX, caspase 3, and caspase 9), Notch signaling pathway markers (Notch1, Jagged1, Hes1, Hes3, Hes5, and Hey1), and autophagic markers (LC3A, LC3B, ATG7, RAB7, LAMP1, and LAMP2). Fluorescence-activated cell sorter profiling was performed for pluripotent markers and putative corneal stem cell markers ABCG2 and p63alpha. RESULTS: The protein and mRNA expression levels of the pluripotent markers were lower, whereas those of the putative stem/progenitor markers ABCG2, DeltaNp63alpha, and Notch signaling molecules (Notch1 and Jagged1) were elevated in limbal cultures. The gene expression levels of the autophagy markers (LC3A, LC3B, and LAMP1) were significantly increased in the limbal cultures compared to the oral and conjunctival cultures. CONCLUSIONS: In conclusion, the limbal epithelial cultures showed higher expression of proliferative, limbal stem cell marker, Notch signaling, and autophagy markers suggesting a role in stem cell maintenance and differentiation. This implicates the probable factors that might drive a successful transplantation. Our findings provide the initial steps toward understanding transplantation medicine in an ex vivo model. PMID- 26283866 TI - Measuring impact and impacting practice. PMID- 26283867 TI - [Not Available]. PMID- 26283868 TI - Registered respiratory therapists as force multipliers in interprofessional complex continuing care. PMID- 26283869 TI - A needs assessment to determine the need for respiratory therapy in complex continuing care: A methods paper. AB - BACKGROUND: There is an emerging demand for complex continuing care for patients who are too ill to safely return home, but for whom hospitalization in an acute care environment is unnecessary or inappropriate. Despite the need and medical complexity of these patients, few respiratory therapists are practising in this environment, and little evidence exists to guide the implementation of respiratory therapy services in this setting. OBJECTIVE: In response to a perceived need for greater respiratory services at Saint Vincent Hospital (Ottawa, Ontario), a needs assessment was undertaken to assess the prevalence of respiratory diseases and for increased respiratory therapist coverage at this complex continuing care hospital. METHODS: An initial literature review was conducted to guide the assessment, and identified only one tool of relevance, which was obtained and formed the basis of the further development of tools for collecting data at the hospital level and on patient care units at the facility. This needs assessment tool was expanded to include priority areas of relevance that fall within the scope of practice of respiratory therapists, and was supplemented by the analysis of administrative databases and qualitative data gathered through unit walkthroughs and unstructured key informant interviews. A health systems framework was used to structure recommendations for the development of interventions and programs for this patient population. RESULTS: The burden of respiratory disease was significant, and included a high prevalence of inhaled medication and oxygen use, and a significant workload that could be attributed to addressing the respiratory needs of patients. CONCLUSION: A range of tools and methods are needed to conduct needs assessments for respiratory therapy in complex continuing care. Using multiple data sources, a significant burden of respiratory diseases was present at the Saint Vincent Hospital; further studies in other complex continuing care hospitals are needed to understand the significance of these findings among this patient population more generally. PMID- 26283870 TI - Endotracheal suctioning practices of nurses and respiratory therapists: How well do they align with clinical practice guidelines? AB - BACKGROUND: A common procedure within intensive care units (ICUs) is the suctioning of respiratory secretions in patients who have been intubated or who have undergone tracheostomy. Previous studies have shown a wide variation in suctioning practices, and although current evidence does not support the routine practice of normal saline instillation (NSI), anecdotally, this is believed to be a common practice. OBJECTIVE: To examine the suctioning practices of registered nurses (RNs) and registered respiratory therapists (RRTs) in six hospital ICUs in Ontario, with special attention devoted to the use of NSI. METHODS: A 24 question, self-administered survey was distributed to 180 participants (90 RNs and 90 RRTs) working in the ICU of six hospitals in Ontario. The survey addressed individual suctioning practices within the ICU. RESULTS: The survey response rate was 96%. There were many similarities between the RRT and RN groups, with both reporting high use of NSI. Both groups observed side effects following NSI with suctioning including decreased oxygen saturation, patient agitation and increased volume of secretions. A significant number of participants from both the RN and RRT groups were unaware of the existence of suctioning and/or NSI protocols in the ICU. Some respondents reported that they routinely suctioned mechanically ventilated patients rather than as required. CONCLUSION: RNs and RRTs continue to practice NSI despite evidence-based practice guidelines suggesting that this therapy may be detrimental to patients. Increased awareness of best practices with respect to endotracheal tube suction generally, and NSI specifically, should be the focus of professional education in both groups of ICU staff. PMID- 26283871 TI - Coaching patients during pulmonary function testing: A practical guide. AB - Pulmonary function tests are an important tool to assist in the diagnosis and management of patients with respiratory disease. Ensuring that the tests are of acceptable quality is vital. Acceptable pulmonary function test quality requires, among others, optimal patient performance. Optimal patient performance, in turn, requires adequate coaching from registered respiratory therapists (RRTs) and other pulmonary function laboratory personnel. The present article provides techniques and tips to help RRTs coach patients during testing. The authors briefly review the components of pulmonary function testing, then describe factors that may hinder a patient's performance, list common mistakes that patients make during testing, and provide tips that RRTs can use to help patients optimize their performance. PMID- 26283872 TI - Innovation in respiratory therapy and the use of three-dimensional printing for tracheostomy management. AB - Technological advances have influenced practice patterns and innovation in many health disciplines, including respiratory therapy. Collaborative approaches and knowledge-sharing environments are vital in addressing problems and adopting emerging technology. This article illustrates how the emergence of low-cost three dimensional printing technology to physically reproduce the results of computed tomography imaging data can provide ways to assess airway abnormalities and symptomology not explained by traditional diagnostic methods. PMID- 26283873 TI - Erratum. AB - [This corrects the article on p. 11 in vol. 51, PMID: 26078622.][This corrects the article on p. 19 in vol. 51, PMID: 26078624.]. PMID- 26283874 TI - Corrigendum. AB - [This corrects the article on p. 39 in vol. 51, PMID: 26089737.]. PMID- 26283875 TI - Effects of Remifentanil Preconditioning on Osteoblasts under Hypoxia Reoxygenation Condition. AB - BACKGROUND: Ischemia-reperfusion of bone occurs in a variety of clinical conditions, such as orthopedic arthroplasty, plastic gnathoplasty, spinal surgery, and amputation. Usually, cellular models of hypoxia-reoxygenation reflect in vivo models of ischemia-reperfusion. With respect to hypoxia reoxygenation conditions, the effects of remifentanil on osteogenesis have received little attention. Therefore, we investigated the effects of remifentanil on the proliferation and differentiation of osteoblasts during hypoxic reoxygenation. METHODS: After remifentanil (0.1, 1 ng/mL) preconditioning for 2 hours, human osteoblasts were cultured under 1% oxygen tension for 24 hours. Thereafter, the cells were reoxygenated for 12 hours at 37 degrees C. The naloxone groups were treated with naloxone for 30 minutes before remifentanil treatment. We measured cell viability via MTT assay. Osteoblast maturation was determined by assay of bone nodular mineralization. Quantitative PCR and western blot methods were used to determine BMP-2, osteocalcin, Akt, type I collagen, osterix, TGF-beta1, HIF-1alpha, and RUNX2 expression levels. RESULTS: Osteoblast viability and bone nodular mineralization by osteoblasts is recovered by remifentanil preconditioning from hypoxia-reoxygenation insult. During hypoxic reoxygenation condition, remifentanil preconditioning induced the expression of BMP-2, osteocalcin, Akt, type I collagen, osterix, TGF-beta1, HIF-1alpha, and RUNX2 in osteoblasts. CONCLUSIONS: Under hypoxia-reoxygenation conditions, remifentanil preconditioning enhanced the cell viability and maturation of osteoblasts, and stimulated the expression of proteins associated with osteoblast proliferation and differentiation of the osteoblast. Our results suggest that remifentanil may help in the treatment of bone stress injuries. PMID- 26283876 TI - Dysregulated Serum MicroRNA Expression Profile and Potential Biomarkers in Hepatitis C Virus-infected Patients. AB - OBJECTIVES: Circulating microRNAs (miRNAs) play critical roles in pathogen-host interactions. Aberrant miRNA expression profiles might have specific characteristics for virus strains, and could serve as noninvasive biomarkers for screening and diagnosing infectious diseases. In this study, we aimed to find new potential miRNA biomarkers of hepatitis C virus (HCV) infection. METHODS: Expression levels of broad-spectrum miRNAs in serum samples from 10 patients with HCV viremia and 10 healthy volunteers were analyzed using miRNA PCR arrays. Subsequently, the differential expression of four selected miRNAs (miR-122, miR 134, miR-424-3p, and miR-629-5p) was verified by qRT-PCR in the serum of 39 patients compared with that in 29 healthy controls. Receiver operating characteristic (ROC) curve analysis was performed to evaluate their potential for the diagnosis of HCV infection. RESULTS: miRNA PCR array assays revealed differential expression of 106 miRNAs in sera of HCV patients compared with that in healthy controls. Serum hsa-miR-122, miR-134, miR-424-3p, and miR-629-5p were well identified. The ROC curves showed that miR-122, miR-134, miR-424-3p, and miR 629-5p could distinguish HCV patients with preferable sensitivity and specificity. In addition, Correlation analysis indicated serum miR-122 expression was positive correlation with ALT/AST levels. Functional analysis of target proteins of these miRNAs indicated the involvement of viral replication, inflammation, and cell proliferation. CONCLUSION: HCV patients have a broad 'fingerprint' profile with dysregulated serum miRNAs compared with that in healthy controls. Among these, serum hsa-miR-122, miR-134, miR-424-3p, and miR 629-5p are identified as promising indication factors of the serum miRNA profile of HCV infection. Particularly, miR-122 could be one of serum biomarkers for early pathological process of HCV. However, more miRNA biomarkers and biological functions of these miRNAs require further investigation. PMID- 26283877 TI - Incidence and Risk Factors of Acute Kidney Injury after Radical Cystectomy: Importance of Preoperative Serum Uric Acid Level. AB - BACKGROUND: Acute kidney injury (AKI) is a common complication after surgery and increases costs, morbidity, and mortality of hospitalized patients. While radical cystectomy associates significantly with an increased risk of serious complications, including AKI, risk factors of AKI after radical cystectomy has not been reported. This study was performed to determine the incidence and independent predictors of AKI after radical cystectomy. METHODS: All consecutive patients who underwent radical cystectomy in 2001-2013 in a single tertiary-care center were identified. Their demographics, laboratory values, and intraoperative data were recorded. Postoperative AKI was defined and staged according to the Acute Kidney Injury Network criteria on the basis of postoperative changes in creatinine levels. Independent predictors of AKI were identified by univariate and multivariate logistic regression analyses. RESULTS: Of the 238 patients who met the eligibility criteria, 91 (38.2%) developed AKI. Univariate logistic regression analyses showed that male gender, high serum uric acid level, and long operation time associated with the development of AKI. On multivariate logistic regression analysis, preoperative serum uric acid concentration (odds ratio [OR] = 1.251; 95% confidence interval [CI] = 1.048-1.493; P = 0.013) and operation time (OR = 1.005; 95% CI = 1.002-1.008; P = 0.003) remained as independent predictors of AKI after radical cystectomy. CONCLUSIONS: AKI after radical cystectomy was a relatively common complication. Its independent risk factors were high preoperative serum uric acid concentration and long operation time. These observations can help to prevent AKI after radical cystectomy. PMID- 26283878 TI - Lifestyle and Risk of Hypertension: Follow-Up of a Young Pre-Hypertensive Cohort. AB - OBJECTIVES: To determine whether healthy lifestyle decreases the risk of developing hypertension in pre-hypertensive patients. STUDY DESIGN: A longitudinal study. SETTING & PARTICIPANTS: Randomly selected pre-hypertensive young adults 20-45 years old without any vascular disease such as stroke or diabetes. PREDICTORS: Four lifestyle factors (a body mass index [BMI] of 18.5 24.9 kg/m2, regular physical activity, no alcohol use and 6-8 h of sleep per day), individually and in combination. OUTCOMES: Hypertension was defined as a systolic blood pressure (SBP) >= 140 mmHg, or a diastolic BP (DBP) >= 90 mmHg or self-reported hypertension. MEASUREMENTS: Multivariate adjusted Cox proportional hazards. RESULTS: During a median follow-up of 4.7 years, 1009 patients were enrolled in our study, and 182 patients developed hypertension. Compared with a BMI of 18.5-24.9 kg/m2, a BMI of 25-30 kg/m2 and a BMI of >30 kg/m2 were associated with an increased risk of hypertension occurrence (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.19-2.84 and HR, 2.62; 95% CI, 1.01-6.80, respectively). Compared with sleep duration of >8 h/day, 6-8 h/day of sleep was associated with a lower risk of hypertension occurrence (HR, 0.40; 95% CI, 0.18 0.86). There were no statistically significant associations between physical activity or alcohol use and hypertension occurrence (P>0.05). LIMITATION: All lifestyle factors were measured only once. CONCLUSION: Healthy BMI (18.5-24.9 kg/m(2)) and sleep duration (6-8 h/day) were associated with a lower risk of the occurrence of hypertension in pre-hypertension patients. PMID- 26283879 TI - Relationship between the hs-CRP as non-specific biomarker and Alzheimer's disease according to aging process. AB - BACKGROUND: Microglia are involved in immune surveillance in intact brains and become activated in response to inflammation and neurodegeneration. Microglia have different functions, neuroprotective or neurotoxic, according to aging in patients with PD. The clinical effect of microglia in patients with Alzheimer's disease (AD) is poorly defined. This prospective study was conducted to investigate the clinical effects of microglia according to the aging process in newly diagnosed AD. METHODS: We examined 532 patients with newly diagnosed AD and 119 healthy controls, and the differences in hs-CRP between these groups were investigated. The patients with AD were classified into 3 subgroups according to age of newly diagnosed AD to investigate the relationship between hs-CRP and the aging process in newly diagnosed AD. RESULTS: There was significantly higher serum high-sensitivity C-reactive protein (hs-CRP), levels in patients with AD compared with healthy controls. A post-hoc analysis of the 3 AD subgroups showed no significant differences in serum hs-CRP level between each group. CONCLUSION: We assumed that neuroinflammation play a role in the pathogenesis of AD, but found no clinical evidence that microglia senescence underlies the microglia switch from neuroprotective in young brains to neurotoxic in aged brains. To clarify the role of microglia and aging in the pathogenesis of AD, future longitudinal studies involving a large cohort are required. PMID- 26283880 TI - Anemia as an Independent Predictor of Adverse Cardiac Outcomes in Patients with Atrial Fibrillation. AB - BACKGROUND: Anemia and echocardiographic systolic and diastolic parameters are useful predictors of cardiovascular outcomes in patients with atrial fibrillation (AF). However, no studies have evaluated the use of anemia for predicting cardiovascular outcome in AF patients when the important echocardiographic parameters are known. Therefore, this study was designed to evaluate whether low hemoglobin is a useful parameter for predicting poor cardiac outcome after adjustment for important echocardiographic parameters in AF patients. METHODS: Index beat method was used to measure echocardiographic parameters in 166 patients with persistent AF. Cardiac events were defined as death and hospitalization for heart failure. The association of hemoglobin with adverse cardiac events was assessed by Cox proportional hazards model. RESULTS: The 49 cardiac events identified in this population included 21 deaths and 28 hospitalizations for heart failure during an average follow-up of 20 months (25th 75th percentile: 14-32 months). Multivariable analysis showed that increased left ventricular mass index (LVMI) and decreased body mass index, estimated glomerular filtration rate, and hemoglobin (hazard ratio 0.827; P = 0.015) were independently associated with increased cardiac events. Additionally, tests of a Cox model that included important clinic variables, LVMI, left ventricular ejection fraction, and the ratio of transmitral E-wave velocity to early diastolic mitral annulus velocity showed that including hemoglobin significantly increased value in predicting adverse cardiac events (P = 0.010). CONCLUSIONS: Hemoglobin is a useful parameter for predicting adverse cardiac events, and including hemoglobin may improve the prognostic prediction of conventional clinical and echocardiographic parameters in patients with AF. PMID- 26283881 TI - Preventing and Treating Hypoxia: Using a Physiology Simulator to Demonstrate the Value of Pre-Oxygenation and the Futility of Hyperventilation. AB - INTRODUCTION: Insufficient pre-oxygenation before emergency intubation, and hyperventilation after intubation are mistakes that are frequently observed in and outside the operating room, in clinical practice and in simulation exercises. Physiological parameters, as appearing on standard patient monitors, do not alert to the deleterious effects of low oxygen saturation on coronary perfusion, or that of low carbon dioxide concentrations on cerebral perfusion. We suggest the use of HumMod, a computer-based human physiology simulator, to demonstrate beneficial physiological responses to pre-oxygenation and the futility of excessive minute ventilation after intubation. METHODS: We programmed HumMod, to A.) compare varying times (0-7 minutes) of pre-oxygenation on oxygen saturation (SpO2) during subsequent apnoea; B.) simulate hyperventilation after apnoea. We compared the effect of different minute ventilation rates on SpO2, acid-base status, cerebral perfusion and other haemodynamic parameters. RESULTS: A.) With no pre-oxygenation, starting SpO2 dropped from 98% to 90% in 52 seconds with apnoea. At the other extreme, following full pre-oxygenation with 100% O2 for 3 minutes or more, the SpO2 remained 100% for 7.75 minutes during apnoea, and dropped to 90% after another 75 seconds. B.) Hyperventilation, did not result in more rapid normalization of SpO2, irrespective of the level of minute ventilation. However, hyperventilation did cause significant decreases in cerebral blood flow (CBF). CONCLUSIONS: HumMod accurately simulates the physiological responses compared to published human studies of pre-oxygenation and varying post intubation minute ventilations, and it can be used over wider ranges of parameters than available in human studies and therefore available in the literature. PMID- 26283882 TI - Risk Factors of Myopic Shift among Primary School Children in Beijing, China: A Prospective Study. AB - OBJECTIVE: To evaluate factors associated with myopic shift among primary school children. METHODS: In a one-year prospective school-based study, 5052 children from ten schools were enrolled using a multi-stage random cluster approach. The baseline examination included non-cycloplegic auto-refractometry and questionnaire interview. Measurements were repeated at the follow-up. RESULTS: Among 5052 students at baseline investigated, 4292 students (85.0%) returned for the follow-up examination. The mean refractive error (-1.13+/-1.57 diopters) had changed -0.52+/-0.73 diopters from the baseline to the follow-up examination. 2170 (51.0%) had a rate of significant myopic shift (significant myopic shift is defined as the change of spherical equivalent of the refraction <= -0.50D between the follow-up and baseline measures). We confirmed that common associated factors (older age, parental myopia, lower refractive status at baseline, shorter reading distance and lower frequency of outdoor activities during class recesses) were associated with greater shift towards myopia. After controlling for age, sex, region of habitation, parental myopia and refractive status at baseline, greater shift towards myopia was independently associated with distance from near-work (OR=1.48 , 95% CI=1.26-1.74, P<0.001) and longer time outdoors for leisure (OR=0.87, 95% CI=0.78-0.97, P<0.013). CONCLUSION: Greater shift towards myopia was independently associated with modifiable factors (distance from near-work and longer time outdoors for leisure) might suggest that encouraging children to go outside for outdoor activities during class recess and after school may be a promising and feasible intervention against myopia development. PMID- 26283883 TI - Increased Expressions of Integrin Subunit beta1, beta2 and beta3 in Patients with Acute Infection. AB - OBJECTIVE: Our previous studies have shown that integrin subunits beta1, beta2 and beta3 were the core proteins of venous thrombi and potential useful biomarker of venous thromboembolism (VTE). Patients with acute infection have a high risk of VTE. In this study we explored that is there any relevance between core proteins and acute infection. METHODS: A total of 230 patients (112 females) with clinically proven acute infection in the emergency unit were recruited into this study, meanwhile 230 patients without acute infection matched in sex and age were recruited as control group. Flow cytometry was done to measure the expressions of blood integrin beta1, beta2, beta3 and cellular immunity (CD3, CD4, CD8, CD4/CD8, CD16CD56 and CD19). The association degree between increased core proteins and acute infection was analyzed by calculating the relative risk (RR). RESULTS: The expression of integrin beta1, beta2 and beta3 was markedly increased in patients with acute infection (P=0.000, 0.000 and 0.015, respectively). The relative risk ratio (RR) of increased integrin beta1, beta2 and beta3 in acute infection patients was 1.424 (95%CI: 1.156-1.755, P=0.001), 1.535 (95%CI: 1.263-1.865, P=0.000) and 1.20 (95%CI: 0.947-1.521, P=0.148), respectively. Combined integrin beta1, beta2 and beta3 analysis showed that the relative risk ratio (RR) of increased in patients with acute infection was 2.962 (95%CI: 1.621-5.410, P=0.001), and this relative risk (RR) rise to 3.176 (95%CI: 1.730-5.829, P=0.000) in patients with respiratory tract infection (RTI). CONCLUSION: As the core proteins of venous thrombi, integrinbeta1, beta2 and beta3 were markedly increased expression in patients with acute infection, which maybe explain the increased risk of VTE in acute infection patients. A weakened immune system could be the basic condition of VTE occurrence. PMID- 26283884 TI - A Randomized Clinical Trial of Nefopam versus Ketorolac Combined With Oxycodone in Patient-Controlled Analgesia after Gynecologic Surgery. AB - OBJECTIVES: Nefopam is a centrally-acting non-opioid analgesic, which has no effect on bleeding time and platelet aggregation. There has been no study about nefopam and oxycodone combination for postoperative analgesia. In this study, we present efficacy and side effects of nefopam/oxycodone compared with ketorolac/oxycodone in patient-controlled analgesia (PCA) after gynecologic surgery. METHODS: 120 patients undergoing gynecologic surgery were divided randomly into two groups: Nefopam group treated with oxycodone 1 mg and nefopam 1 mg bolus; and Ketorolac group treated with oxycodone 1 mg and ketorolac 1.5 mg bolus. After the operation, a blinded observer assessed the pain with a numeric rating scale (NRS), infused PCA dose and sedation score at 1, 4, 24, and 48 h, nausea, vomiting, headache, shivering, pruritus and delirium at 6, 24 and 48 h, and satisfaction at 48 h after the operation. RESULTS: Nefopam group showed less nausea than Ketorolac group within 6 h after the operation. There were no significant differences in demographic data and other complications between both groups. At 48 h after operation, satisfaction and the infused PCA volumes of Nefopam group (34.0+/- 19.7 ml) showed no significant differences compared to Ketorolac group (30.7+/- 18.4 ml, P-value= 0.46). CONCLUSION: Nefopam showed a similar efficacy and lower incidence of nausea within 6 h after the operation to that of ketorolac in PCA. Nefopam may be a useful analgesic drug for the opioid based PCA after gynecologic surgery. Further evaluation of accurate equivalent dose of nefopam as well as pharmacokinetics of bolus administration is required. PMID- 26283886 TI - The Role of Autophagy in Kidney Inflammatory Injury via the NF-kappaB Route Induced by LPS. AB - Acute kidney injury (AKI) is a systemic inflammatory response syndrome associated with poor clinical outcomes. No treatments effective for AKI are currently available. Thus, there is an urgent need of development of treatments effective for AKI. Autophagy, an intracellular proteolytic system, is induced in renal cells during AKI. However, whether autophagy is protective or injurious for AKI needs to be clearly clarified. We addressed this question by pharmacological inhibition of autophagy using a mouse model of lipopolysaccharide (LPS) induced AKI. We found that autophagy was induced in renal cortex of mice during LPS induced AKI as reflected by a dose-and time-dependent increased accumulation of light chain 3-II (LC3-II), the common marker of autophagy, compared to that of control group; 2) the occurrence of intensive, punctate and increased immunohistochemical staining image of LC3-II in renal cortex; 3) the significant increase in the expression levels of Beclin-1, another key marker of autophagy; 4) the significantly increased levels of plasma urea and serum creatinine and 5) the significant increase in autophagagosome area ratio. We observed that 3 methyladenine (3-MA), a pharmacological inhibitor of autophagy, blocked autophagy flux, alleviated AKI and protected against LPS-induced AKI. LPS triggered kidney inflammation by activation of the canonical NF-kappaB pathway. This route can be modulated by autophagy. Activation of the canonical NF-kappaB pathway was reduced in 3-MA+LPS as compared to that in LPS-treated group of mice. Mice pretreated with 3-MA before exposure to LPS showed a reduction in p65 phosphorylation, resulting in the accumulation of ubiquitinated IkappaB. In conclusion, impairment of autophagy ameliorates LPS-induced inflammation and decreases kidney injury. The accumulation of ubiquitinated IkappaB may be responsible for this effect. PMID- 26283885 TI - Regulatory and Effector Helper T-Cell Profile after Nerve Xenografting in the Toll-Like Receptor-Deficient Mice. AB - INTRODUCTION: The balance between regulatory T cells (Tregs) and effector T help cells (Th cells) is critical for the control of adaptive immune response during nerve transplantation. However, whether the homeostasis of immune regulation between Tregs and Th cells requires toll-like receptor (TLR) signaling is unclear. The aim of this study is to profile the distribution of spleen Tregs and Th cells in a mouse model of nerve xenografting in the TLR2 and NF-kappaB gene knockout mice. METHODS: The sciatic nerve was taken from a SD rat or an allogeneic mouse and transplanted to a right back leg of recipient C57BL/6, TLR2( /-), or NF-kappaB(-/-) mice by subcutaneous transplantation. After 7 days, the T lymphocytes were then isolated from spleen, stained with phenotyping kits, and analyzed by flow cytometry. RESULTS: The results showed that Tregs were decreased after nerve xenografting in the recipient C57BL/6 mouse. In addition, nerve xenografting also increased the Th1 and Th17 but not the Th2 cell populations. In contrast, amelioration of the Tregs elimination was found in TLR2(-/-) and NF kappaB(-/-) mice after transplantation of the nerve xenograft. Moreover, the mice lacking TLR2 or NF-kappaB showed attenuation of the increase in Th1 and Th17 cells after nerve xenografting. CONCLUSIONS: TLR signaling is involved in T cell population regulation during tissue transplantation. Knock-out of TLR2 and NF kappaB prevented Tregs elimination and inhibited Th1- and Th17-driven immune response after nerve xenografting. This study highlighted the potential of inhibiting TLR signaling to modulate T cell-mediated immune regulation to facilitate tolerance to nerve transplantation. PMID- 26283887 TI - The Association of BCG Vaccination with Atopy and Asthma in Adults. AB - INTRODUCTION: There are few studies investigating the association between BCG vaccination and atopy or asthma in adults. OBJECTIVE: We investigated the association between BCG scar and the occurrence of atopy and asthma in Korean adults. METHODS: We carried out a retrospective study of Korean adults who underwent skin prick testing, and, in some cases, spirometry and bronchial provocation tests in a secondary care hospital from April 2010 to February 2011. Atopy status was classified according to allergen/histamine (A/H) ratio of wheal (A/H ratio >= 1, atopy; 0 < A/H ratio < 1, intermediate; A/H ratio = 0, non atopy). A patient with asthma was defined as one who has symptoms compatible with asthma and showed either a positive provocation testing or bronchodilator reversibility. RESULTS: Among 200 participants, neither the presence (intermediate vs. non-atopy: adjusted odds ratio (aOR) 0.83; 95% CI 0.26, 2.60; p = 0.75, atopy vs. non-atopy: aOR 0.89; 95% CI 0.33, 2.37; p = 0.81, respectively). nor the size of BCG scar was significantly associated with atopy status. However, among those patients who underwent either bronchodilator response testing or bronchial provocation testing, the presence of BCG scar (aOR 0.33; CI 0.14, 0.77; p = 0.01) and the size of BCG scar were inversely associated with asthma. (p = 0.01) CONCLUSIONS: We found a significant association between BCG scar and asthmatic status in Korean adults, although there was no significant association between either the presence or size of BCG scar and atopy. PMID- 26283888 TI - Arsenic Trioxide Activate Transcription of Heme Oxygenase-1 by Promoting Nuclear Translocation of NFE2L2. AB - In a previous study, we found that induced expression of Heme Oxygenase-1 (HO-1) is responsible for the resistance of human osteosarcoma MG63 cells to the chemotherapeutic agent arsenic trioxide (ATO). The present study was aimed at investigating the molecular mechanisms underlying the induction of HO-1 that occurs after exposure of MG63 cells to ATO. First, using RT-QPCT and Western blot, we found that ATO strongly induced the expression of heme oxygenase-1 (HO 1) in these human osteosarcoma cells. Then by analyzing HO-1 mRNA of MG63 cells exposed to ATO in the presence and absence of a transcription inhibitor Actinomycin-D (Act-D), we demonstrated that ATO activates HO-1 expression in MG63 cells by regulating the transcription of the gene. Finally, through the analysis of the NFE2L2 protein levels among the total cellular and nuclear proteins by Western-blot and Immunocytochemical staning, we determined that ATO enhanced the nuclear translocation of nuclear factor erythroid 2-like 2 (NFE2L2), also known as Nrf2. From these results we have concluded that transcription activation of HO 1 resulting from the nuclear translocation of NFE2L2 is the underlying molecular mechanism for its high induction, which, in turn, is responsible for the resistance of human osteosarcoma cells to ATO treatment. PMID- 26283889 TI - Serum biomarkers VEGF-C and IL-6 are associated with severe human Peripheral Artery Stenosis. AB - BACKGROUND: Emerging reports propose possible biomarkers that are related to inflammation, nutrition and lipid parameters for detection of the progression of atherosclerotic plaques, peripheral artery disease (PAD) and particularly peripheral artery stenosis (PAS). However, it remains unclear which biomarkers in serum are associated with the severity of PAS. FINDINGS: In this study, we measured serum levels of inflammatory biomarkers along with lipid and nutritional parameters in 53 patients who suffered different degrees of PAS. Serum concentrations of vascular endothelial growth factor-c (VEGF-C) and IL-6 (Interleukin 6) were significantly increased in patients showing moderate or severe PAS. Furthermore, the number of blood monocytes from PAS patients was significantly increased, which showed elevated adhesion to plate-coated fibrinogen. Compared to healthy subjects, freshly isolated or LPS (lipopolysaccharide)-stimulated blood monocytes from PAS patients could produce VEGF-C and IL-6 at higher levels. CONCLUSIONS: Our study suggests that the increased number of blood monocytes might play key roles during the development of severe PAS, which enhance adhesion at the local narrowed peripheral artery and secret high levels of VEGF-C and IL-6. We suggest that serum concentrations of VEGF-C and IL-6 might be used as biomarkers for diagnosis severe PAS in combination with clinical imaging examination. PMID- 26283890 TI - The prevalence of occult leiomyosarcoma at surgery for presumed uterine fibroids: a meta-analysis. AB - There is a concern regarding the risk of occult leiomyosarcomas found at surgery for presumed benign fibroids. We sought to produce a comprehensive review of published data addressing this issue and provide high-quality prevalence estimates for clinical practice and future research. A comprehensive literature search using the PubMed/MEDLINE database and the Cochrane Library was performed. Inclusion criteria were human studies, peer-reviewed, with original data, involving cases for surgery in which fibroid-related indications were the primary reason for surgery, and histopathology was provided. Candidate studies (4864) were found; 3844 were excluded after review of the abstract. The remaining 1020 manuscripts were reviewed in their entirety, and 133 were included in the Bayesian binomial random effect meta-analysis. The estimated rate of leiomyosarcoma was 0.51 per 1000 procedures (95 % credible interval (CrI) 0.16 0.98) or approximately 1 in 2000. Restricting the meta-analysis to the 64 prospective studies resulted in a substantially lower estimate of 0.12 leiomyosarcomas per 1000 procedures (95 % CrI <0.01-0.75) or approximately 1 leiomyosarcoma per 8300 surgeries. Results suggest that the prevalence of occult leiomyosarcomas at surgery for presumed uterine fibroids is much less frequent than previously estimated. This rate should be incorporated into both clinical practice and future research. PMID- 26283891 TI - Anxiety at outpatient hysteroscopy. AB - This review summarises current understanding and research on the association between anxiety and outpatient hysteroscopy. Women undergoing hysteroscopy suffer from significant levels of anxiety, with repercussions on pain perception, success rates and satisfaction. Using validated tools such as the Spielberger State-Trait Anxiety Index (STAI) or the Hospital Anxiety and Depression Scale (HADS) in the outpatient hysteroscopy setting, average state anxiety scores similar or greater than those measured before more invasive procedures under general anaesthesia have been consistently reported. This clearly suggests a significant gap between our clinical viewpoint of what is "minimally invasive" and patients' expectations. In spite of its potential role of confounder in studies on pain-reduction interventions, we found that patient anxiety was evaluated in only 9 (13 %) out of a sample of 70 randomised controlled trials on outpatient hysteroscopy published since 1992. Factors such as trait anxiety, age, indication and the efficiency of the clinic can be correlated to state anxiety before hysteroscopy, but more robust data are needed. Promising non pharmacological interventions to reduce anxiety at hysteroscopy include patient education, communication through traditional or multimedia approaches, interaction and support during the procedure and music listening. PMID- 26283892 TI - Cortical alpha activity predicts the confidence in an impending action. AB - When we make a decision, we experience a degree of confidence that our choice may lead to a desirable outcome. Recent studies in animals have probed the subjective aspects of the choice confidence using confidence-reporting tasks. These studies showed that estimates of the choice confidence substantially modulate neural activity in multiple regions of the brain. Building on these findings, we investigated the neural representation of the confidence in a choice in humans who explicitly reported the confidence in their choice. Subjects performed a perceptual decision task in which they decided between choosing a button press or a saccade while we recorded EEG activity. Following each choice, subjects indicated whether they were sure or unsure about the choice. We found that alpha activity strongly encodes a subject's confidence level in a forthcoming button press choice. The neural effect of the subjects' confidence was independent of the reaction time and independent of the sensory input modeled as a decision variable. Furthermore, the effect is not due to a general cognitive state, such as reward expectation, because the effect was specifically observed during button press choices and not during saccade choices. The neural effect of the confidence in the ensuing button press choice was strong enough that we could predict, from independent single trial neural signals, whether a subject was going to be sure or unsure of an ensuing button press choice. In sum, alpha activity in human cortex provides a window into the commitment to make a hand movement. PMID- 26283893 TI - Barriers to developing a valid rodent model of Alzheimer's disease: from behavioral analysis to etiological mechanisms. AB - Sporadic Alzheimer's disease (AD) is the most prevalent form of age-related dementia. As such, great effort has been put forth to investigate the etiology, progression, and underlying mechanisms of the disease. Countless studies have been conducted, however, the details of this disease remain largely unknown. Rodent models provide opportunities to investigate certain aspects of AD that cannot be studied in humans. These animal models vary from study to study and have provided some insight, but no real advancements in the prevention or treatment of the disease. In this Hypothesis and Theory paper, we discuss what we perceive as barriers to impactful discovery in rodent AD research and we offer potential solutions for moving forward. Although no single model of AD is capable of providing the solution to the growing epidemic of the disease, we encourage a comprehensive approach that acknowledges the complex etiology of AD with the goal of enhancing the bidirectional translatability from bench to bedside and vice versa. PMID- 26283896 TI - Identification of pyridine analogs as new predator-derived kairomones. AB - In the wild, animals have developed survival strategies relying on their senses. The individual ability to identify threatening situations is crucial and leads to increase in the overall fitness of the species. Rodents, for example have developed in their nasal cavities specialized olfactory neurons implicated in the detection of volatile cues encoding for impending danger such as predator scents or alarm pheromones. In particular, the neurons of the Grueneberg ganglion (GG), an olfactory subsystem, are implicated in the detection of danger cues sharing a similar chemical signature, a heterocyclic sulfur- or nitrogen-containing motif. Here we used a "from the wild to the lab" approach to identify new molecules that are involuntarily emitted by predators and that initiate fear-related responses in the recipient animal, the putative prey. We collected urines from carnivores as sources of predator scents and first verified their impact on the blood pressure of the mice. With this approach, the urine of the mountain lion emerged as the most potent source of chemical stress. We then identified in this biological fluid, new volatile cues with characteristic GG-related fingerprints, in particular the methylated pyridine structures, 2,4-lutidine and its analogs. We finally verified their encoded danger quality and demonstrated their ability to mimic the effects of the predator urine on GG neurons, on mice blood pressure and in behavioral experiments. In summary, we were able to identify here, with the use of an integrative approach, new relevant molecules, the pyridine analogs, implicated in interspecies danger communication. PMID- 26283897 TI - Group-level component analyses of EEG: validation and evaluation. AB - Multi-subject or group-level component analysis provides a data-driven approach to study properties of brain networks. Algorithms for group-level data decomposition of functional magnetic resonance imaging data have been brought forward more than a decade ago and have significantly matured since. Similar applications for electroencephalographic data are at a comparatively early stage of development though, and their sensitivity to topographic variability of the electroencephalogram or loose time-locking of neuronal responses has not yet been assessed. This study investigates the performance of independent component analysis (ICA) and second order blind source identification (SOBI) for data decomposition, and their combination with either temporal or spatial concatenation of data sets, for multi-subject analyses of electroencephalographic data. Analyses of simulated sources with different spatial, frequency, and time locking profiles, revealed that temporal concatenation of data sets with either ICA or SOBI served well to reconstruct sources with both strict and loose time locking, whereas performance decreased in the presence of topographical variability. The opposite pattern was found with a spatial concatenation of subject-specific data sets. This study proofs that procedures for group-level decomposition of electroencephalographic data can be considered valid and promising approaches to infer the latent structure of multi-subject data sets. Yet, specific implementations need further adaptations to optimally address sources of inter-subject and inter-trial variance commonly found in EEG recordings. PMID- 26283895 TI - Turning over DNA methylation in the mind. AB - Cytosine DNA methylation is a stable epigenetic modification with established roles in regulating transcription, imprinting, female X-chromosome inactivation, and silencing of transposons. Dynamic gain or loss of DNA methylation reshapes the genomic landscape of cells during early differentiation, and in post-mitotic mammalian brain cells these changes continue to accumulate throughout the phases of cortical maturation in childhood and adolescence. There is also evidence for dynamic changes in the methylation status of specific genomic loci during the encoding of new memories, and these epigenome dynamics could play a causal role in memory formation. However, the mechanisms that may dynamically regulate DNA methylation in neurons during memory formation and expression, and the function of such epigenomic changes in this context, are unclear. Here we discuss the possible roles of DNA methylation in encoding and retrieval of memory. PMID- 26283894 TI - Ontogenetic shifts in brain scaling reflect behavioral changes in the life cycle of the pouched lamprey Geotria australis. AB - Very few studies have described brain scaling in vertebrates throughout ontogeny and none in lampreys, one of the two surviving groups of the early agnathan (jawless) stage in vertebrate evolution. The life cycle of anadromous parasitic lampreys comprises two divergent trophic phases, firstly filter-feeding as larvae in freshwater and secondly parasitism as adults in the sea, with the transition marked by a radical metamorphosis. We characterized the growth of the brain during the life cycle of the pouched lamprey Geotria australis, an anadromous parasitic lamprey, focusing on the scaling between brain and body during ontogeny and testing the hypothesis that the vast transitions in behavior and environment are reflected in differences in the scaling and relative size of the major brain subdivisions throughout life. The body and brain mass and the volume of six brain structures of G. australis, representing six points of the life cycle, were recorded, ranging from the early larval stage to the final stage of spawning and death. Brain mass does not increase linearly with body mass during the ontogeny of G. australis. During metamorphosis, brain mass increases markedly, even though the body mass does not increase, reflecting an overall growth of the brain, with particularly large increases in the volume of the optic tectum and other visual areas of the brain and, to a lesser extent, the olfactory bulbs. These results are consistent with the conclusions that ammocoetes rely predominantly on non visual and chemosensory signals, while adults rely on both visual and olfactory cues. PMID- 26283898 TI - Molecular programs induced by heat acclimation confer neuroprotection against TBI and hypoxic insults via cross-tolerance mechanisms. AB - Neuroprotection following prolonged exposure to high ambient temperatures (heat acclimation HA) develops via altered molecular programs such as cross-tolerance Heat Acclimation-Neuroprotection Cross-Tolerance (HANCT). The mechanisms underlying cross-tolerance depend on enhanced "on-demand" protective pathways evolving during acclimation. The protection achieved is long lasting and limits the need for de novo recruitment of cytoprotective pathways upon exposure to novel stressors. Using mouse and rat acclimated phenotypes, we will focus on the impact of heat acclimation on Angiotensin II-AT2 receptors in neurogenesis and on HIF-1 as key mediators in spontaneous recovery and HANCT after traumatic brain injury (TBI). The neuroprotective consequences of heat acclimation on NMDA and AMPA receptors will be discussed using the global hypoxia model. A behavioral molecular link will be crystallized. The differences between HANCT and consensus preconditioning will be reviewed. PMID- 26283899 TI - Effects of corticotropin releasing factor (CRF) on sleep and temperature following predictable controllable and uncontrollable stress in mice. AB - Corticotropin releasing factor (CRF) is a major mediator of central nervous system responses to stressors, including alterations in wakefulness and sleep. However, its role in mediating stress-induced alterations in sleep has not been fully delineated. In this study, we assessed the role of CRF and the non-specific CRF antagonist, astressin (AST), in regulating changes in sleep produced by signaled, escapable shock (SES) and signaled inescapable shock (SIS), two stressors that can increase or decrease sleep, respectively. Male BALB/cJ mice were surgically implanted with transmitters (DataSciences ETA10-F20) for recording EEG, activity and core body temperature by telemetry and a cannula for intracerebroventricular (ICV) microinjections. After baseline (Base) sleep recording, mice were presented tones (90 dB, 2 kHz) that started 5.0 s prior to and co-terminated with footshock (0.5 mA; 5.0 s maximum duration). SES mice (n = 9) always received shock but could terminate it by moving to the non-occupied chamber in a shuttlebox. Yoked SIS mice (n = 9) were treated identically, but could not alter shock duration. Training with SES or SIS was conducted over 2 days to stabilize responses. Afterwards, the mice received saline, CRF [0.4 MUg (0.42 mM) or AST (1.0 MUg (1.4 mM)] prior to SES or SIS. Sleep was analyzed over 20 h post-stress recordings. After administration of saline, REM was significantly greater in SES mice than in SIS mice whereas after CRF or AST, REM was similar in both groups. Total 20 h NREM did not vary across condition or group. However, after administration of saline and CRF, NREM episode duration was significantly decreased, and NREM episode number significantly increased, in SIS mice compared to SES animals. SES and SIS mice showed similar stress induced hyperthermia (SIH) across all conditions. These data demonstrate that CRF can mediate stress-induced changes in sleep independently of SIH, an index of hypothalamic-pituitary-adrenal axis activation. PMID- 26283901 TI - Researching children's individual empathic abilities in the context of their daily lives: the importance of mixed methods. AB - In social neuroscience, empathy is often approached as an individual ability, whereas researchers in anthropology focus on empathy as a dialectic process between agents. In this perspective paper, we argue that to further elucidate the mechanisms underlying the development of empathy, social neuroscience research should draw on insights and methods from anthropology. First, we discuss neuropsychological studies that investigate empathy in inter-relational contexts. Second, we highlight differences between the social neuroscience and anthropological conceptualizations of empathy. Third, we introduce a new study design based on a mixed method approach, and present initial results from one classroom that was part of a larger study and included 28 children (m = 13, f = 15). Participants (aged 9-11) were administered behavioral tasks and a social network questionnaire; in addition an observational study was also conducted over a period of 3 months. Initial results showed how children's expressions of their empathic abilities were influenced by situational cues in classroom processes. This effect was further explained by children's positions within classroom networks. Our results emphasize the value of interdisciplinary research in the study of empathy. PMID- 26283900 TI - Does neuroinflammation turn on the flame in Alzheimer's disease? Focus on astrocytes. AB - Data from animal models and Alzheimer's disease (AD) subjects provide clear evidence for an activation of inflammatory pathways during the pathogenetic course of such illness. Biochemical and neuropathological studies highlighted an important cause/effect relationship between inflammation and AD progression, revealing a wide range of genetic, cellular, and molecular changes associated with the pathology. In this context, glial cells have been proved to exert a crucial role. These cells, in fact, undergo important morphological and functional changes and are now considered to be involved in the onset and progression of AD. In particular, astrocytes respond quickly to pathology with changes that have been increasingly recognized as a continuum, with potentially beneficial and/or negative consequences. Although it is now clear that activated astrocytes trigger the neuroinflammatory process, however, the precise mechanisms have not been completely elucidated. Neuroinflammation is certainly a multi faceted and complex phenomenon and, especially in the early stages, exerts a reparative intent. However, for reasons not yet all well known, this process goes beyond the physiologic control and contributes to the exacerbation of the damage. Here we scrutinize some evidence supporting the role of astrocytes in the neuroinflammatory process and the possibility that these cells could be considered a promising target for future AD therapies. PMID- 26283902 TI - Chemostimuli for guanylyl cyclase-D-expressing olfactory sensory neurons promote the acquisition of preferences for foods adulterated with the rodenticide warfarin. AB - Many animals have the ability to acquire food preferences from conspecifics via social signals. For example, the coincident detection of a food odor by canonical olfactory sensory neurons (OSNs) and agonists of the specialized OSNs expressing the receptor guanylyl cyclase GC-D (GC-D+ OSNs) will promote a preference in recipient rodents for similarly odored foods. It has been hypothesized that these preferences are acquired and maintained regardless of the palatability or quality of the food. We assessed whether mice could acquire and maintain preferences for food that had been adulterated with the anticoagulant rodenticide warfarin. After olfactory investigation of a saline droplet containing either cocoa (2%, w/w) or cinnamon (1%, w/w) along with a GC-D+ OSN-specific chemostimulus (either of the guanylin-family peptides uroguanylin and guanylin; 1-50 nM), C57BL/6J mice exhibited robust preferences for unadulterated food containing the demonstrated odor. The peptide-dependent preference was observed even when the food contained warfarin (0.025% w/w). Repeated ingestion of warfarin-containing food over four days did not disrupt the preference, even though mice were not re-exposed to the peptide stimulus. Surprisingly, mice continued to prefer warfarin-adulterated food containing the demonstrated odor when presented with a choice of warfarin free food containing a novel odor. Our results indicate that olfactory-mediated food preferences can be acquired and maintained for warfarin-containing foods and suggest that guanylin peptides may be effective stimuli for promoting the ingestion of foods or other edibles with low palatability or potential toxicity. PMID- 26283903 TI - Are single odorous components of a predator sufficient to elicit defensive behaviors in prey species? AB - When exposed to the odor of a sympatric predator, prey animals typically display escape or defensive responses. These phenomena have been well-documented, especially in rodents, when exposed to the odor of a cat, ferret, or fox. As a result of these experiments new discussions center on the following questions: (1) is a single volatile compound such as a major or a minor mixture constituent in urine or feces, emitted by the predator sufficient to cause defensive reactions in a potential prey species or (2) is a whole array of odors required to elicit a response and (3) will the relative size or escapability of the prey as compared to the predator influence responsiveness. Most predator-prey studies on this topic have been performed in the laboratory or under semi-natural conditions. Field studies could help to find answers to these questions. Australian mammals are completely naive toward the introduced placental carnivores. That offers ideal opportunities to analyze in the field the responses of potential prey species to unknown predator odors. During the last decades researchers have accumulated an enormous amount of data exploring the effects of eutherian predator odors on native marsupial mammals. In this review, we will give a survey about the development of olfactory research, chemical signals and their influence on the behavior and-in some cases-physiology of prey species. In addition, we report on the effects of predator odor experiments performed under natural conditions in Australia. When studying all these literature we learned that data gained under controlled laboratory conditions elucidate the role of individual odors on brain structures and ultimately on a comparatively narrow range behaviors. In contrast to single odors odor arrays mimic much more the situation prey animals are confronted to in nature. Therefore, a broad range of methodology-from chemistry to ecology including anatomy, physiology, and behavior is needed to understand all the different (relevant) stimuli that govern and guide the interactions between a predator and its potential prey. PMID- 26283905 TI - In vivo comparison of the charge densities required to evoke motor responses using novel annular penetrating microelectrodes. AB - Electrodes for cortical stimulation need to deliver current to neural tissue effectively and safely. We have developed electrodes with a novel annular geometry for use in cortical visual prostheses. Here, we explore a critical question on the ideal annulus height to ensure electrical stimulation will be safe and effective. We implanted single electrodes into the motor cortex of anesthetized rats and measured the current required to evoke a motor response to stimulation, and the charge injection capacity (CIC) of the electrodes. We compared platinum iridium (PtIr) electrodes with different annulus heights, with and without a coating of porous titanium nitride (TiN). Threshold charge densities to evoke a motor response ranged from 12 to 36 MUC.cm(-2).ph(-1). Electrodes with larger geometric surface areas (GSAs) required higher currents to evoke responses, but lower charge densities. The addition of a porous TiN coating did not significantly influence the current required to evoke a motor response. The CIC of both electrode types was significantly reduced in vivo compared with in vitro measurements. The measured CIC was 72 and 18 MUC.cm(-2).ph(-1) for electrodes with and without a TiN coating, respectively. These results support the use of PtIr annular electrodes with annulus heights greater than 100 MUm (GSA of 38, 000 MUm(2)). However, if the electrodes are coated with porous TiN the annulus height can be reduced to 40 MUm (GSA of 16,000 MUm(2)). PMID- 26283904 TI - The unfolded protein response in multiple sclerosis. AB - The unfolded protein response (UPR) occurs in response to endoplasmic reticulum (ER) stress caused by the accumulation of unfolded or misfolded proteins in the ER. The UPR is comprised of three signaling pathways that promote cytoprotective functions to correct ER stress; however, if ER stress cannot be resolved the UPR results in apoptosis of affected cells. The UPR is an important feature of various human diseases, including multiple sclerosis (MS). Recent studies have shown several components of the UPR are upregulated in the multiple cell types in MS lesions, including oligodendrocytes, T cells, microglia/macrophages, and astrocytes. Data from animal model studies, particularly studies of experimental autoimmune encephalomyelitis (EAE) and the cuprizone model, imply an important role of the UPR activation in oligodendrocytes in the development of MS. In this review we will cover current literature on the UPR and the evidence for its role in the development of MS. PMID- 26283906 TI - Cluster imaging of multi-brain networks (CIMBN): a general framework for hyperscanning and modeling a group of interacting brains. AB - Studying the neural basis of human social interactions is a key topic in the field of social neuroscience. Brain imaging studies in this field usually focus on the neural correlates of the social interactions between two participants. However, as the participant number further increases, even by a small amount, great difficulties raise. One challenge is how to concurrently scan all the interacting brains with high ecological validity, especially for a large number of participants. The other challenge is how to effectively model the complex group interaction behaviors emerging from the intricate neural information exchange among a group of socially organized people. Confronting these challenges, we propose a new approach called "Cluster Imaging of Multi-brain Networks" (CIMBN). CIMBN consists of two parts. The first part is a cluster imaging technique with high ecological validity based on multiple functional near infrared spectroscopy (fNIRS) systems. Using this technique, we can easily extend the simultaneous imaging capacity of social neuroscience studies up to dozens of participants. The second part of CIMBN is a multi-brain network (MBN) modeling method based on graph theory. By taking each brain as a network node and the relationship between any two brains as a network edge, one can construct a network model for a group of interacting brains. The emergent group social behaviors can then be studied using the network's properties, such as its topological structure and information exchange efficiency. Although there is still much work to do, as a general framework for hyperscanning and modeling a group of interacting brains, CIMBN can provide new insights into the neural correlates of group social interactions, and advance social neuroscience and social psychology. PMID- 26283907 TI - Erratum: In vivo comparison of the charge densities required to evoke motor responses using novel annular penetrating microelectrodes. AB - [This corrects the article on p. 265 in vol. 9, PMID: 26029097.]. PMID- 26283908 TI - Sphingosine kinase 2-deficiency mediated changes in spinal pain processing. AB - Chronic pain is one of the most burdensome health issues facing the planet (as costly as diabetes and cancer combined), and in desperate need for new diagnostic targets leading to better therapies. The bioactive lipid sphingosine 1-phosphate (S1P) and its receptors have recently been shown to modulate nociceptive signaling at the level of peripheral nociceptors and central neurons. However, the exact role of S1P generating enzymes, in particular sphingosine kinase 2 (Sphk2), in nociception remains unknown. We found that both sphingosine kinases, Sphk1 and Sphk2, were expressed in spinal cord (SC) with higher levels of Sphk2 mRNA compared to Sphk1. All three Sphk2 mRNA-isoforms were present with the Sphk2.1 mRNA showing the highest relative expression. Mice deficient in Sphk2 (Sphk2(-/-)) showed in contrast to mice deficient in Sphk1 (Sphk1(-/-)) substantially lower spinal S1P levels compared to wild-type C57BL/6 mice. In the formalin model of acute peripheral inflammatory pain, Sphk2(-/-) mice showed facilitation of nociceptive transmission during the late response, whereas responses to early acute pain, and the number of c-Fos immunoreactive dorsal horn neurons were not different between Sphk2(-/-) and wild-type mice. Chronic peripheral inflammation (CPI) caused a bilateral increase in mechanical sensitivity in Sphk2(-/-) mice. Additionally, CPI increased the relative mRNA expression of P2X4 receptor, brain-derived neurotrophic factor and inducible nitric oxide synthase in the ipsilateral SC of wild-type but not Sphk2(-/-) mice. Similarly, Sphk2(-/-) mice showed in contrast to wild-type no CPI-dependent increase in areas of the dorsal horn immunoreactive for the microglia marker Iba 1 and the astrocyte marker Glial fibrillary acidic protein (GFAP). Our results suggest that the tightly regulated cell signaling enzyme Sphk2 may be a key component for facilitation of nociceptive circuits in the CNS leading to central sensitization and pain memory formation. PMID- 26283910 TI - Systemic AAVrh10 provides higher transgene expression than AAV9 in the brain and the spinal cord of neonatal mice. AB - Systemic delivery of self-complementary (sc) adeno-associated-virus vector of serotype 9 (AAV9) was recently shown to provide robust and widespread gene transfer to the central nervous system (CNS), opening new avenues for practical, and non-invasive gene therapy of neurological diseases. More recently, AAV of serotype rh10 (AAVrh10) was also found highly efficient to mediate CNS transduction after intravenous administration in mice. However, only a few studies compared AAV9 and AAVrh10 efficiencies, particularly in the spinal cord. In this study, we compared the transduction capabilities of AAV9 and AAVrh10 in the brain, the spinal cord, and the peripheral nervous system (PNS) after intravenous delivery in neonatal mice. As reported in previous studies, AAVrh10 achieved either similar or higher transduction than AAV9 in all the examined brain regions. The superiority of AAVrh10 over AAV9 appeared statistically significant only in the medulla and the cerebellum, but a clear trend was also observed in other structures like the hippocampus or the cortex. In contrast to previous studies, we found that AAVrh10 was more efficient than AAV9 for transduction of the dorsal spinal cord and the lower motor neurons (MNs). However, differences between the two serotypes appeared mainly significant at low dose, and surprisingly, increasing the dose did not improve AAVrh10 distribution in the spinal cord, in contrary to AAV9. Similar dose-related differences between transduction efficiency of the two serotypes were also observed in the sciatic nerve. These findings suggest differences in the transduction mechanisms of these two serotypes, which both hold great promise for gene therapy of neurological diseases. PMID- 26283911 TI - Evaluation of the amyloid beta-GFP fusion protein as a model of amyloid beta peptides-mediated aggregation: a study of DNAJB6 chaperone. AB - Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the accumulation and aggregation of extracellular amyloid beta (Abeta) peptides and intracellular aggregation of hyper-phosphorylated tau protein. Recent evidence indicates that accumulation and aggregation of intracellular amyloid beta peptides may also play a role in disease pathogenesis. This would suggest that intracellular Heat Shock Proteins (HSP) that maintain cellular protein homeostasis might be candidates for disease amelioration. We recently found that DNAJB6, a member of DNAJ family of heat shock proteins, effectively prevented the aggregation of short aggregation-prone peptides containing large poly glutamines (associated with CAG repeat diseases) both in vitro and in cells. Moreover, recent in vitro data showed that DNAJB6 can delay the aggregation of Abeta42 peptides. In this study, we investigated the ability of DNAJB6 to prevent the aggregation of extracellular and intracellular Abeta peptides using transfection of human embryonic kidney 293 (HEK293) cells with Abeta-green fluorescent protein (GFP) fusion construct and performing western blotting and immunofluorescence techniques. We found that DNAJB6 indeed suppresses Abeta-GFP aggregation, but not seeded aggregation initiated by extracellular Abeta peptides. Unexpectedly and unlike what we found for peptide-mediated aggregation, DNAJB6 required interaction with HSP70 to prevent the aggregation of the Abeta GFP fusion protein and its J-domain was crucial for its anti-aggregation effect. In addition, other DNAJ proteins as well as HSPA1a overexpression also suppressed Abeta-GFP aggregation efficiently. Our findings suggest that Abeta aggregation differs from poly glutamine (Poly Q) peptide induced aggregation in terms of chaperone handling and sheds doubt on the usage of Abeta-GFP fusion construct for studying Abeta peptide aggregation in cells. PMID- 26283914 TI - Origins of spontaneous activity in the degenerating retina. AB - Sensory deafferentation resulting from the loss of photoreceptors during retinal degeneration (rd) is often accompanied by a paradoxical increase in spontaneous activity throughout the visual system. Oscillatory discharges are apparent in retinal ganglion cells in several rodent models of rd, indicating that spontaneous activity can originate in the retina. Understanding the biophysical mechanisms underlying spontaneous retinal activity is interesting for two main reasons. First, it could lead to strategies that reduce spontaneous retinal activity, which could improve the performance of vision restoration strategies that aim to stimulate remnant retinal circuits in blind patients. Second, studying emergent network activity could offer general insights into how sensory systems remodel upon deafferentation. Here we provide an overview of the work describing spontaneous activity in the degenerating retina, and outline the current state of knowledge regarding the cellular and biophysical properties underlying spontaneous neural activity. PMID- 26283912 TI - Diseases associated with leaky hemichannels. AB - Hemichannels (HCs) and gap junction channels (GJCs) formed by protein subunits called connexins (Cxs) are major pathways for intercellular communication. While HCs connect the intracellular compartment with the extracellular milieu, GJCs allow the interchange of molecules between cytoplasm of two contacting cells. Under physiological conditions, HCs are mostly closed, but they can open under certain stimuli allowing the release of autocrine and paracrine molecules. Moreover, some pathological conditions, like ischemia or other inflammation conditions, significantly increase HCs activity. In addition, some mutations in Cx genes associated with human diseases, such as deafness or cataracts, lead to the formation of more active HCs or "leaky HCs." In this article we will revise cellular and molecular mechanisms underlying the appearance of leaky HCs, and the consequences of their expression in different cellular systems and animal models, in seeking a common pattern or pathological mechanism of disease. PMID- 26283913 TI - Age-related hearing impairment and the triad of acquired hearing loss. AB - Understanding underlying pathological mechanisms is prerequisite for a sensible design of protective therapies against hearing loss. The triad of age-related, noise-generated, and drug-induced hearing loss displays intriguing similarities in some cellular responses of cochlear sensory cells such as a potential involvement of reactive oxygen species (ROS) and apoptotic and necrotic cell death. On the other hand, detailed studies have revealed that molecular pathways are considerably complex and, importantly, it has become clear that pharmacological protection successful against one form of hearing loss will not necessarily protect against another. This review will summarize pathological and pathophysiological features of age-related hearing impairment (ARHI) in human and animal models and address selected aspects of the commonality (or lack thereof) of cellular responses in ARHI to drugs and noise. PMID- 26283909 TI - Myelin damage and repair in pathologic CNS: challenges and prospects. AB - Injury to the central nervous system (CNS) results in oligodendrocyte cell death and progressive demyelination. Demyelinated axons undergo considerable physiological changes and molecular reorganizations that collectively result in axonal dysfunction, degeneration and loss of sensory and motor functions. Endogenous adult oligodendrocyte precursor cells and neural stem/progenitor cells contribute to the replacement of oligodendrocytes, however, the extent and quality of endogenous remyelination is suboptimal. Emerging evidence indicates that optimal remyelination is restricted by multiple factors including (i) low levels of factors that promote oligodendrogenesis; (ii) cell death among newly generated oligodendrocytes, (iii) inhibitory factors in the post-injury milieu that impede remyelination, and (iv) deficient expression of key growth factors essential for proper re-construction of a highly organized myelin sheath. Considering these challenges, over the past several years, a number of cell-based strategies have been developed to optimize remyelination therapeutically. Outcomes of these basic and preclinical discoveries are promising and signify the importance of remyelination as a mechanism for improving functions in CNS injuries. In this review, we provide an overview on: (1) the precise organization of myelinated axons and the reciprocal axo-myelin interactions that warrant properly balanced physiological activities within the CNS; (2) underlying cause of demyelination and the structural and functional consequences of demyelination in axons following injury and disease; (3) the endogenous mechanisms of oligodendrocyte replacement; (4) the modulatory role of reactive astrocytes and inflammatory cells in remyelination; and (5) the current status of cell-based therapies for promoting remyelination. Careful elucidation of the cellular and molecular mechanisms of demyelination in the pathologic CNS is a key to better understanding the impact of remyelination for CNS repair. PMID- 26283916 TI - Cocaine promotes oxidative stress and microglial-macrophage activation in rat cerebellum. AB - Different mechanisms have been suggested for cocaine neurotoxicity, including oxidative stress alterations. Nuclear factor kappa B (NF-kappaB), considered a sensor of oxidative stress and inflammation, is involved in drug toxicity and addiction. NF-kappaB is a key mediator for immune responses that induces microglial/macrophage activation under inflammatory processes and neuronal injury/degeneration. Although cerebellum is commonly associated to motor control, muscular tone, and balance. Its relation with addiction is getting relevance, being associated to compulsive and perseverative behaviors. Some reports indicate that cerebellar microglial activation induced by cannabis or ethanol, promote cerebellar alterations and these alterations could be associated to addictive related behaviors. After considering the effects of some drugs on cerebellum, the aim of the present work analyzes pro-inflammatory changes after cocaine exposure. Rats received daily 15 mg/kg cocaine i.p., for 18 days. Reduced and oxidized forms of glutathione (GSH) and oxidized glutathione (GSSG), glutathione peroxidase (GPx) activity and glutamate were determined in cerebellar homogenates. NF-kappaB activity, CD68, and GFAP expression were determined. Cerebellar GPx activity and GSH/GSSG ratio are significantly decreased after cocaine exposure. A significant increase of glutamate concentration is also observed. Interestingly, increased NF-kappaB activity is also accompanied by an increased expression of the lysosomal mononuclear phagocytic marker ED1 without GFAP alterations. Current trends in addiction biology are focusing on the role of cerebellum on addictive behaviors. Cocaine-induced cerebellar changes described herein fit with previosus data showing cerebellar alterations on addict subjects and support the proposed role of cerebelum in addiction. PMID- 26283917 TI - A delicate balance: role of MMP-9 in brain development and pathophysiology of neurodevelopmental disorders. AB - The extracellular matrix (ECM) is a critical regulator of neural network development and plasticity. As neuronal circuits develop, the ECM stabilizes synaptic contacts, while its cleavage has both permissive and active roles in the regulation of plasticity. Matrix metalloproteinase 9 (MMP-9) is a member of a large family of zinc-dependent endopeptidases that can cleave ECM and several cell surface receptors allowing for synaptic and circuit level reorganization. It is becoming increasingly clear that the regulated activity of MMP-9 is critical for central nervous system (CNS) development. In particular, MMP-9 has a role in the development of sensory circuits during early postnatal periods, called 'critical periods.' MMP-9 can regulate sensory-mediated, local circuit reorganization through its ability to control synaptogenesis, axonal pathfinding and myelination. Although activity-dependent activation of MMP-9 at specific synapses plays an important role in multiple plasticity mechanisms throughout the CNS, misregulated activation of the enzyme is implicated in a number of neurodegenerative disorders, including traumatic brain injury, multiple sclerosis, and Alzheimer's disease. Growing evidence also suggests a role for MMP 9 in the pathophysiology of neurodevelopmental disorders including Fragile X Syndrome. This review outlines the various actions of MMP-9 during postnatal brain development, critical for future studies exploring novel therapeutic strategies for neurodevelopmental disorders. PMID- 26283918 TI - Microtechnologies for studying the role of mechanics in axon growth and guidance. AB - The guidance of axons to their proper targets is not only a crucial event in neurodevelopment, but also a potential therapeutic target for neural repair. Axon guidance is mediated by various chemo- and haptotactic cues, as well as the mechanical interactions between the cytoskeleton and the extracellular matrix (ECM). Axonal growth cones, dynamic ends of growing axons, convert external stimuli to biochemical signals, which, in turn, are translated into behavior, e.g., turning or retraction, via cytoskeleton-matrix linkages. Despite the inherent mechanical nature of the problem, the role of mechanics in axon guidance is poorly understood. Recent years has witnessed the application of a range of microtechnologies in neurobiology, from microfluidic circuits to single molecule force spectroscopy. In this mini-review, we describe microtechnologies geared towards dissecting the mechanical aspects of axon guidance, divided into three categories: controlling the growth cone microenvironment, stimulating growth cones with externally applied forces, and measuring forces exerted by the growth cones. A particular emphasis is given to those studies that combine multiple techniques, as dictated by the complexity of the problem. PMID- 26283915 TI - Elusive roles for reactive astrocytes in neurodegenerative diseases. AB - Astrocytes play crucial roles in the brain and are involved in the neuroinflammatory response. They become reactive in response to virtually all pathological situations in the brain such as axotomy, ischemia, infection, and neurodegenerative diseases (ND). Astrocyte reactivity was originally characterized by morphological changes (hypertrophy, remodeling of processes) and the overexpression of the intermediate filament glial fibrillary acidic protein (GFAP). However, it is unclear how the normal supportive functions of astrocytes are altered by their reactive state. In ND, in which neuronal dysfunction and astrocyte reactivity take place over several years or decades, the issue is even more complex and highly debated, with several conflicting reports published recently. In this review, we discuss studies addressing the contribution of reactive astrocytes to ND. We describe the molecular triggers leading to astrocyte reactivity during ND, examine how some key astrocyte functions may be enhanced or altered during the disease process, and discuss how astrocyte reactivity may globally affect ND progression. Finally we will consider the anticipated developments in this important field. With this review, we aim to show that the detailed study of reactive astrocytes may open new perspectives for ND. PMID- 26283919 TI - Mice lacking the synaptic adhesion molecule Neph2/Kirrel3 display moderate hyperactivity and defective novel object preference. AB - Synaptic adhesion molecules regulate diverse aspects of neuronal synapse development, including synapse specificity, formation, and maturation. Neph2, also known as Kirrel3, is an immunoglobulin superfamily adhesion molecule implicated in intellectual disability, neurocognitive delay associated with Jacobsen syndrome, and autism spectrum disorders. We here report mice lacking Neph2 (Neph2(-/-) mice) display moderate hyperactivity in a familiar, but not novel, environment and defective novel object recognition with normal performances in Morris water maze spatial learning and memory, contextual fear conditioning and extinction, and pattern separation tests. These mice also show normal levels of anxiety-like behaviors, social interaction, and repetitive behaviors. At the synapse level, Neph2(-/-) dentate gyrus granule cells exhibit unaltered dendritic spine density and spontaneous excitatory synaptic transmission. These results suggest that Neph2 is important for normal locomotor activity and object recognition memory. PMID- 26283921 TI - Assessing effects on dendritic arborization using novel Sholl analyses. AB - Determining the shape of cell-specific dendritic arbors is a tightly regulated process that occurs during development. When this regulation is aberrant, which occurs during disease or injury, alterations in dendritic shape result in changes to neural circuitry. There has been significant progress on characterizing extracellular and intrinsic factors that regulate dendrite number by our laboratory and others. Generally, changes to the dendritic arbor are assessed by Sholl analysis or simple dendrite counting. However, we have found that this general method often overlooks local changes to the arbor. Previously, we developed a program (titled Bonfire) to facilitate digitization of neurite morphology and subsequent Sholl analysis and to assess changes to root, intermediate, and terminal neurites. Here, we apply these different Sholl analyses, and a novel Sholl analysis, to uncover previously unknown changes to the dendritic arbor when we overexpress an important regulator of dendrite branching, cytosolic PSD-95 interactor (cypin), at two developmental time points. Our results suggest that standard Sholl analysis and simple dendrite counting are not sufficient for uncovering local changes to the dendritic arbor. PMID- 26283920 TI - Modulation of TLR3/TLR4 inflammatory signaling by the GABAB receptor agonist baclofen in glia and immune cells: relevance to therapeutic effects in multiple sclerosis. AB - The GABAB receptor agonist, baclofen, is used to treat muscle tightness and cramping caused by spasticity in a number of disorders including multiple sclerosis (MS), but its precise mechanism of action is unknown. Neuroinflammation drives the central pathology in MS and is mediated by both immunoreactive glial cells and invading lymphocytes. Furthermore, a body of data indicates that the Toll-like receptor (TLR) family of innate immune receptors is implicated in MS progression. In the present study we investigated whether modulation of GABAB receptors using baclofen can exert anti-inflammatory effects by targeting TLR3 and(or) TLR4-induced inflammatory signaling in murine glial cells and human peripheral blood mononuclear cells (PBMCs) isolated from healthy control individuals and patients with the relapse-remitting (RR) form of MS. TLR3 and TLR4 stimulation promoted the nuclear sequestration of NF-kappaB and pro inflammatory cytokine expression in murine glia, while TLR4, but not TLR3, promoted pro-inflammatory cytokine expression in PBMCs isolated from both healthy donors and RR-MS patients. Importantly, this effect was exacerbated in RR-MS patient immune cells. We present further evidence that baclofen dose-dependently attenuated TLR3- and TLR4-induced inflammatory signaling in primary glial cells. Pre-exposure of PBMCs isolated from healthy donors to baclofen attenuated TLR4 induced TNF-alpha expression, but did not affect TLR4-induced TNF-alpha expression in RR-MS patient PBMCs. Interestingly, mRNA expression of the GABAB receptor was reduced in PBMCs from RR-MS donors when compared to healthy controls, an effect that might contribute to the differential sensitivity to baclofen seen in healthy and RR-MS patient cells. Overall these findings indicate that baclofen differentially regulates TLR3 and TLR4 signaling in glia and immune cells, and offers insight on the role of baclofen in the treatment of neuroinflammatory disease states including MS. PMID- 26283922 TI - Cortical interneurons migrating on a pure substrate of N-cadherin exhibit fast synchronous centrosomal and nuclear movements and reduced ciliogenesis. AB - The embryonic development of the cortex involves a phase of long distance migration of interneurons born in the basal telencephalon. Interneurons first migrate tangentially and then reorient their trajectories radially to enter the developing cortex. We have shown that migrating interneurons can assemble a primary cilium, which maintains the centrosome to the plasma membrane and processes signals to control interneuron trajectory (Baudoin et al., 2012). In the developing cortex, N-cadherin is expressed by migrating interneurons and by cells in their migratory pathway. N-cadherin promotes the motility and maintains the polarity of tangentially migrating interneurons (Luccardini et al., 2013). Because N-cadherin is an important factor that regulates the migration of medial ganglionic eminence (MGE) cells in vivo, we further characterized the motility and polarity of MGE cells on a substrate that only comprises this protein. MGE cells migrating on a N-cadherin substrate were seven times faster than on a laminin substrate and two times faster than on a substrate of cortical cells. A primary cilium was much less frequently observed on MGE cells migrating on N cadherin than on laminin. Nevertheless, the mature centriole (MC) frequently docked to the plasma membrane in MGE cells migrating on N-cadherin, suggesting that plasma membrane docking is a basic feature of the centrosome in migrating MGE cells. On the N-cadherin substrate, centrosomal and nuclear movements were remarkably synchronous and the centrosome remained near the nucleus. Interestingly, MGE cells with cadherin invalidation presented centrosomal movements no longer coordinated with nuclear movements. In summary, MGE cells migrating on a pure substrate of N-cadherin show fast, coordinated nuclear and centrosomal movements, and rarely present a primary cilium. PMID- 26283923 TI - Hunting for origins of migraine pain: cluster analysis of spontaneous and capsaicin-induced firing in meningeal trigeminal nerve fibers. AB - Trigeminal nerves in meninges are implicated in generation of nociceptive firing underlying migraine pain. However, the neurochemical mechanisms of nociceptive firing in meningeal trigeminal nerves are little understood. In this study, using suction electrode recordings from peripheral branches of the trigeminal nerve in isolated rat meninges, we analyzed spontaneous and capsaicin-induced orthodromic spiking activity. In control, biphasic single spikes with variable amplitude and shapes were observed. Application of the transient receptor potential vanilloid 1 (TRPV1) agonist capsaicin to meninges dramatically increased firing whereas the amplitudes and shapes of spikes remained essentially unchanged. This effect was antagonized by the specific TRPV1 antagonist capsazepine. Using the clustering approach, several groups of uniform spikes (clusters) were identified. The clustering approach combined with capsaicin application allowed us to detect and to distinguish "responder" (65%) from "non-responder" clusters (35%). Notably, responders fired spikes at frequencies exceeding 10 Hz, high enough to provide postsynaptic temporal summation of excitation at brainstem and spinal cord level. Almost all spikes were suppressed by tetrodotoxin (TTX) suggesting an involvement of the TTX-sensitive sodium channels in nociceptive signaling at the peripheral branches of trigeminal neurons. Our analysis also identified transient (desensitizing) and long-lasting (slowly desensitizing) responses to the continuous application of capsaicin. Thus, the persistent activation of nociceptors in capsaicin-sensitive nerve fibers shown here may be involved in trigeminal pain signaling and plasticity along with the release of migraine related neuropeptides from TRPV1 positive neurons. Furthermore, cluster analysis could be widely used to characterize the temporal and neurochemical profiles of other pain transducers likely implicated in migraine. PMID- 26283924 TI - Osteogenesis and neurogenesis: a robust link also for language evolution. PMID- 26283926 TI - Editorial: Dynamics of cyclic nucleotide signaling in neurons. PMID- 26283925 TI - Inner retinal change in a novel rd1-FTL mouse model of retinal degeneration. AB - While photoreceptor loss is the most devastating result of inherited retinal degenerations such as retinitis pigmentosa, inner retinal neurons also undergo significant alteration. Detailing these changes has become important as many vision restorative therapies target the remaining neurons. In this study, the rd1 Fos-Tau-LacZ (rd1-FTL) mouse model was used to explore inner retinal change at a late stage of retinal degeneration, after the loss of photoreceptor nuclei. The rd1-FTL model carries a mutation in the phosphodiesterase gene, Pde6b, and an axonally targeted transgenic beta galactosidase reporter system under the control of the c-fos promoter. Retinae of transgenic rd1-FTL mice and control FTL animals aged 2-12 months were processed for indirect fluorescence immunocytochemistry. At 2 months of age, a time when the majority of photoreceptor nuclei are lost, there was negligible c-fos reporter (FTL) expression, however, from 4 months, reporter expression was observed to increase within subpopulations of amacrine and ganglion cells within the central retina. These areas of inner retinal FTL expression coincided with regions that contained aberrant Muller cells. Specifically, these cells exhibited reduced glutamine synthetase and Kir4.1 immunolabelling, whilst showing evidence of proliferative gliosis (increased cyclinD1 and glial fibrillary acidic protein expression). These changes were limited to distinct regions where cone photoreceptor terminals were absent. Overall, these results highlight that distinct areas of the rd1-FTL central retina undergo significant glial alterations after cone photoreceptor loss. These areas coincide with up-regulation of the c-fos reporter in the inner retina, which may represent a change in neuronal function/plasticity. The rd1-FTL mouse is a useful model system to probe changes that occur in the inner retina at later stages of retinal degeneration. PMID- 26283927 TI - Neural circuits revealed. PMID- 26283928 TI - A voxelwise approach to determine consensus regions-of-interest for the study of brain network plasticity. AB - Despite exciting advances in the functional imaging of the brain, it remains a challenge to define regions of interest (ROIs) that do not require investigator supervision and permit examination of change in networks over time (or plasticity). Plasticity is most readily examined by maintaining ROIs constant via seed-based and anatomical-atlas based techniques, but these approaches are not data-driven, requiring definition based on prior experience (e.g., choice of seed region, anatomical landmarks). These approaches are limiting especially when functional connectivity may evolve over time in areas that are finer than known anatomical landmarks or in areas outside predetermined seeded regions. An ideal method would permit investigators to study network plasticity due to learning, maturation effects, or clinical recovery via multiple time point data that can be compared to one another in the same ROI while also preserving the voxel-level data in those ROIs at each time point. Data-driven approaches (e.g., whole-brain voxelwise approaches) ameliorate concerns regarding investigator bias, but the fundamental problem of comparing the results between distinct data sets remains. In this paper we propose an approach, aggregate-initialized label propagation (AILP), which allows for data at separate time points to be compared for examining developmental processes resulting in network change (plasticity). To do so, we use a whole-brain modularity approach to parcellate the brain into anatomically constrained functional modules at separate time points and then apply the AILP algorithm to form a consensus set of ROIs for examining change over time. To demonstrate its utility, we make use of a known dataset of individuals with traumatic brain injury sampled at two time points during the first year of recovery and show how the AILP procedure can be applied to select regions of interest to be used in a graph theoretical analysis of plasticity. PMID- 26283930 TI - Editorial: Dendritic spines: from shape to function. PMID- 26283929 TI - Knowing a synapse when you see one. AB - Recent years have seen a rapidly growing recognition of the complexity and diversity of the myriad individual synaptic connections that define brain synaptic networks. It has also become increasingly apparent that the synapses themselves are a major key to understanding the development, function and adaptability of those synaptic networks. In spite of this growing appreciation, the molecular, structural and functional characteristics of individual synapses and the patterning of their diverse characteristics across functional networks have largely eluded quantitative study with available imaging technologies. Here we offer an overview of new computational imaging methods that promise to bring single-synapse analysis of synaptic networks to the fore. We focus especially on the challenges and opportunities associated with quantitative detection of individual synapses and with measuring individual synapses across network scale populations in mammalian brain. PMID- 26283931 TI - Diversity in olfactory bulb size in birds reflects allometry, ecology, and phylogeny. AB - The relative size of olfactory bulbs (OBs) is correlated with olfactory capabilities across vertebrates and is widely used to assess the relative importance of olfaction to a species' ecology. In birds, variations in the relative size of OBs are correlated with some behaviors; however, the factors that have led to the high level of diversity seen in OB sizes across birds are still not well understood. In this study, we use the relative size of OBs as a neuroanatomical proxy for olfactory capabilities in 135 species of birds, representing 21 orders. We examine the scaling of OBs with brain size across avian orders, determine likely ancestral states and test for correlations between OB sizes and habitat, ecology, and behavior. The size of avian OBs varied with the size of the brain and this allometric relationship was for the most part isometric, although species did deviate from this trend. Large OBs were characteristic of more basal species and in more recently derived species the OBs were small. Living and foraging in a semi-aquatic environment was the strongest variable driving the evolution of large OBs in birds; olfaction may provide cues for navigation and foraging in this otherwise featureless environment. Some of the diversity in OB sizes was also undoubtedly due to differences in migratory behavior, foraging strategies and social structure. In summary, relative OB size in birds reflect allometry, phylogeny and behavior in ways that parallel that of other vertebrate classes. This provides comparative evidence that supports recent experimental studies into avian olfaction and suggests that olfaction is an important sensory modality for all avian species. PMID- 26283933 TI - Electrical stimulation of the superior colliculus induces non-topographically organized perturbation of reaching movements in cats. AB - Besides its well-known contribution to orienting behaviors, the superior colliculus (SC) might also play a role in controlling visually guided reaching movements. This view has been inferred from studies in monkeys showing that some tectal cells located in the deep layers are active prior to reaching movements; it was corroborated by functional imaging studies performed in humans. Likewise, our group has already demonstrated that, in cats, SC electrical stimulation can modify the trajectory of goal-directed forelimb movements without necessarily affecting the gaze position. However, as in monkeys, we could not establish any congruence between the usual retinotopic SC map and direction of evoked forelimb movements, albeit only a small portion of the collicular map was investigated. Therefore, the aim of the current study was to further ascertain the causal contribution of SC to reaching movement by exploring the whole collicular map. Our results confirmed that SC electrical stimulation deflected the trajectory of reaching movements, but this deviation was always directed downward and backward, irrespective of the location of the stimulation site. The lack of a complete map of reach directions in the SC and the absence of congruence between the direction of evoked forelimb movements and the collicular oculomotor map challenge the view that, in the cat, the SC causally contributes to coding forelimb movements. Interestingly, the very short latencies of the effect argue also against the interruption of reaching movements being driven by a disruption of the early visual processing. Our results rather suggest that the SC might contribute to the reach target selection process. Alternatively, SC stimulation might have triggered a postural adjustment anticipating an upcoming orienting reaction, leading to an interruption of the on-going reaching movement. PMID- 26283932 TI - Advancing brain-machine interfaces: moving beyond linear state space models. AB - Advances in recent years have dramatically improved output control by Brain Machine Interfaces (BMIs). Such devices nevertheless remain robotic and limited in their movements compared to normal human motor performance. Most current BMIs rely on transforming recorded neural activity to a linear state space composed of a set number of fixed degrees of freedom. Here we consider a variety of ways in which BMI design might be advanced further by applying non-linear dynamics observed in normal motor behavior. We consider (i) the dynamic range and precision of natural movements, (ii) differences between cortical activity and actual body movement, (iii) kinematic and muscular synergies, and (iv) the implications of large neuronal populations. We advance the hypothesis that a given population of recorded neurons may transmit more useful information than can be captured by a single, linear model across all movement phases and contexts. We argue that incorporating these various non-linear characteristics will be an important next step in advancing BMIs to more closely match natural motor performance. PMID- 26283934 TI - Sensorimotor organization of a sustained involuntary movement. AB - Involuntary movements share much of the motor control circuitry used for voluntary movement, yet the two can be easily distinguished. The Kohnstamm phenomenon (where a sustained, hard push produces subsequent involuntary arm raising) is a useful experimental model for exploring differences between voluntary and involuntary movement. Both central and peripheral accounts have been proposed, but little is known regarding how the putative Kohnstamm generator responds to afferent input. We addressed this by obstructing the involuntary upward movement of the arm. Obstruction prevented the rising EMG pattern that characterizes the Kohnstamm. Importantly, once the obstruction was removed, the EMG signal resumed its former increase, suggesting a generator that persists despite peripheral input. When only one arm was obstructed during bilateral involuntary movements, only the EMG signal from the obstructed arm showed the effect. Upon release of the obstacle, the obstructed arm reached the same position and EMG level as the unobstructed arm. Comparison to matched voluntary movements revealed a preserved stretch response when a Kohnstamm movement first contacts an obstacle, and also an overestimation of the perceived contact force. Our findings support a hybrid central and peripheral account of the Kohnstamm phenomenon. The strange subjective experience of this involuntary movement is consistent with the view that movement awareness depends strongly on efference copies, but that the Kohnstamm generator does not produces efference copies. PMID- 26283936 TI - Pain perception in people with Down syndrome: a synthesis of clinical and experimental research. AB - People with an intellectual disability experience both acute and chronic pain with at least the same frequency as the general population. However, considerably less is known about the pain perception of people with Down syndrome. In this review paper, we evaluated the available clinical and experimental evidence. Some experimental studies of acute pain have indicated that pain threshold was higher than normal but only when using a reaction time method to measure pain sensitivity. However, when reaction time is not part of the calculation of the pain threshold, pain sensitivity in people with Down syndrome is in fact lower than normal (more sensitive to pain). Clinical studies of chronic pain have shown that people with an intellectual disability experience chronic pain and within that population, people with Down syndrome also experience chronic pain, but the precise prevalence of chronic pain in Down syndrome has yet to be established. Taken together, the literature suggests that people with Down syndrome experience pain, both acute and chronic, with at least the same frequency as the rest of the population. Furthermore, the evidence suggests that although acute pain expression appears to be delayed, once pain is registered, there appears to be a magnified pain response. We conclude by proposing an agenda for future research in this area. PMID- 26283935 TI - Visual rehabilitation: visual scanning, multisensory stimulation and vision restoration trainings. AB - Neuropsychological training methods of visual rehabilitation for homonymous vision loss caused by postchiasmatic damage fall into two fundamental paradigms: "compensation" and "restoration". Existing methods can be classified into three groups: Visual Scanning Training (VST), Audio-Visual Scanning Training (AViST) and Vision Restoration Training (VRT). VST and AViST aim at compensating vision loss by training eye scanning movements, whereas VRT aims at improving lost vision by activating residual visual functions by training light detection and discrimination of visual stimuli. This review discusses the rationale underlying these paradigms and summarizes the available evidence with respect to treatment efficacy. The issues raised in our review should help guide clinical care and stimulate new ideas for future research uncovering the underlying neural correlates of the different treatment paradigms. We propose that both local "within-system" interactions (i.e., relying on plasticity within peri-lesional spared tissue) and changes in more global "between-system" networks (i.e., recruiting alternative visual pathways) contribute to both vision restoration and compensatory rehabilitation, which ultimately have implications for the rehabilitation of cognitive functions. PMID- 26283937 TI - Acute physical exercise improves shifting in adolescents at school: evidence for a dopaminergic contribution. AB - The executive function of shifting between mental sets demands cognitive flexibility. Based on evidence that physical exercise fostered cognition, we tested whether acute physical exercise can improve shifting in an unselected sample of adolescents. Genetic polymorphisms were analyzed to gain more insight into possibly contributing neurophysiological processes. We examined 297 students aged between 13 and 17 years in their schools. Physical exercise was manipulated by an intense incremental exercise condition using bicycle ergometers and a control condition which involved watching an infotainment cartoon while sitting calm. The order of conditions was counterbalanced between participants. Shifting was assessed by a switching task after both conditions. Acute intense physical exercise significantly improved shifting as indicated by reduced switch costs. Exercise-induced performance gains in switch costs were predicted by a single nucleotide polymorphism (SNP) targeting the Dopamine Transporter (DAT1/SLCA6A3) gene suggesting that the brain dopamine system contributed to the effect. The results demonstrate the potential of acute physical exercise to improve cognitive flexibility in adolescents. The field conditions of the present approach suggest applications in schools. PMID- 26283938 TI - GABAergic feedback signaling into the calyces of the mushroom bodies enables olfactory reversal learning in honey bees. AB - In reversal learning, subjects first learn to respond to a reinforced stimulus A and not to a non-reinforced stimulus B (A(+) vs. B(-)) and then have to learn the opposite when stimulus contingencies are reversed (A(-) vs. B(+)). This change in stimulus valence generates a transitory ambiguity at the level of stimulus outcome that needs to be overcome to solve the second discrimination. Honey bees (Apis mellifera) efficiently master reversal learning in the olfactory domain. The mushroom bodies (MBs), higher-order structures of the insect brain, are required to solve this task. Here we aimed at uncovering the neural circuits facilitating reversal learning in honey bees. We trained bees using the olfactory conditioning of the proboscis extension reflex (PER) coupled with localized pharmacological inhibition of Gamma-AminoButyric Acid (GABA)ergic signaling in the MBs. We show that inhibition of ionotropic but not metabotropic GABAergic signaling into the MB calyces impairs reversal learning, but leaves intact the capacity to perform two consecutive elemental olfactory discriminations with ambiguity of stimulus valence. On the contrary, inhibition of ionotropic GABAergic signaling into the MB lobes had no effect on reversal learning. Our results are thus consistent with a specific requirement of the feedback neurons (FNs) providing ionotropic GABAergic signaling from the MB lobes to the calyces for counteracting ambiguity of stimulus valence in reversal learning. PMID- 26283940 TI - The impact of perceived similarity on tacit coordination: propensity for matching and aversion to decoupling choices. AB - Homophily, or "love for similar others," has been shown to play a fundamental role in the formation of interpersonal ties and social networks. Yet no study has investigated whether perceived similarities can affect tacit coordination. We had 68 participants attempt to maximize real monetary earnings by choosing between a safe but low paying option (that could be obtained with certainty) and a potentially higher paying but "risky" one, which depended on the choice of a matched counterpart. While making their choices participants were mutually informed of whether their counterparts similarly or dissimilarly identified with three person-descriptive words as themselves. We found that similarity increased the rate of "risky" choices only when the game required counterparts to match their choices (stag hunt games). Conversely, similarity led to decreased risk rates when they were to tacitly decouple their choices (entry games). Notably, though similarity increased coordination in the matching environment, it did not did not increase it in the decoupling game. In spite of this, similarity increased (expected) payoffs across both coordination environments. This could shed light on why homophily is so successful as a social attractor. Finally, this propensity for matching and aversion to decoupling choices was not observed when participants "liked" their counterparts but were dissimilar to them. We thus conclude that the impact of similarity of coordination should not be reduced to "liking" others (i.e., social preferences) but it is also about predicting them. PMID- 26283939 TI - Attentional performance is correlated with the local regional efficiency of intrinsic brain networks. AB - Attention is a crucial brain function for human beings. Using neuropsychological paradigms and task-based functional brain imaging, previous studies have indicated that widely distributed brain regions are engaged in three distinct attention subsystems: alerting, orienting and executive control (EC). Here, we explored the potential contribution of spontaneous brain activity to attention by examining whether resting-state activity could account for individual differences of the attentional performance in normal individuals. The resting-state functional images and behavioral data from attention network test (ANT) task were collected in 59 healthy subjects. Graph analysis was conducted to obtain the characteristics of functional brain networks and linear regression analyses were used to explore their relationships with behavioral performances of the three attentional components. We found that there was no significant relationship between the attentional performance and the global measures, while the attentional performance was associated with specific local regional efficiency. These regions related to the scores of alerting, orienting and EC largely overlapped with the regions activated in previous task-related functional imaging studies, and were consistent with the intrinsic dorsal and ventral attention networks (DAN/VAN). In addition, the strong associations between the attentional performance and specific regional efficiency suggested that there was a possible relationship between the DAN/VAN and task performances in the ANT. We concluded that the intrinsic activity of the human brain could reflect the processing efficiency of the attention system. Our findings revealed a robust evidence for the functional significance of the efficiently organized intrinsic brain network for highly productive cognitions and the hypothesized role of the DAN/VAN at rest. PMID- 26283941 TI - The formation and extinction of fear memory in tree shrews. AB - Fear is an emotion that is well-studied due to its importance for animal survival. Experimental animals, such as rats and mice, have been widely used to model fear. However, higher animals such as nonhuman primates have rarely been used to study fear due to ethical issues and high costs. Tree shrews are small mammals that are closely related to primates; they have been used to model human related psychosocial conditions such as stress and alcohol tolerance. Here, we describe an experimental paradigm to study the formation and extinction of fear memory in tree shrews. We designed an experimental apparatus of a light/dark box with a voltage foot shock. We found that tree shrews preferred staying in the dark box in the daytime without stimulation and showed avoidance to voltage shocks applied to the footplate in a voltage-dependent manner. Foot shocks applied to the dark box for 5 days (10 min per day) effectively reversed the light-dark preference of the tree shrews, and this memory lasted for more than 50 days without any sign of memory decay (extinction) in the absence of further stimulation. However, this fear memory was reversed with 4 days of reverse training by applying the same stimulus to the light box. When reducing the stimulus intensity during the training period, a memory extinction and subsequently reinstatement effects were observed. Thus, our results describe an efficient method of monitoring fear memory formation and extinction in tree shrews. PMID- 26283942 TI - Unveiling residual, spontaneous recovery from subtle hemispatial neglect three years after stroke. AB - A common and disabling consequence of stroke is the difficulty in processing contralesional space (i.e., hemispatial neglect). According to paper-and-pencil tests, neglect remits or stabilizes in severity within a few months after a brain injury. This arbitrary temporal limit, however, is at odds with neglect's well known dependency on task-sensitivity. The present study tested the hypothesis that the putative early resolution of neglect might be due to the insensitivity of testing methods rather than to the lack of spontaneous recovery at later stages. A right hemisphere stroke patient was studied longitudinally for 3 years. According to paper-and-pencil tests the patient showed no symptom of hemispatial neglect 1 month post stroke. Awareness of spatially lateralized visual targets was then assessed by means of computer-based single- and dual-tasks requiring an additional top-down deployment of attention for the parallel processing of visual or auditory stimuli. Errorless performance at computer-based tasks was reached at month 12 and maintained until month 29 after stroke. A bottom-up manipulation was then implemented by reducing target diameter. Following this change, more than 50% of contralesional targets were omitted, mostly under dual-tasking. At months 40 and 41 the same task revealed a significant (but not complete) reduction in the number of contralesional omissions. Ipsilesional targets were, in contrast, still errorless detected. The coupling of a bottom-up (target change) and a top down (dual-tasking) manipulation revealed the presence of a long-lasting spontaneous recovery from contralesional spatial awareness deficits. In contrast, neither manipulation was effective when implemented separately. After having excluded the potential confound of practice effects, it was concluded that not only the presence but also the time course of hemispatial neglect strongly depends on the degree of attentional engagement required by the task. PMID- 26283943 TI - Sleep spindle and K-complex detection using tunable Q-factor wavelet transform and morphological component analysis. AB - A novel framework for joint detection of sleep spindles and K-complex events, two hallmarks of sleep stage S2, is proposed. Sleep electroencephalography (EEG) signals are split into oscillatory (spindles) and transient (K-complex) components. This decomposition is conveniently achieved by applying morphological component analysis (MCA) to a sparse representation of EEG segments obtained by the recently introduced discrete tunable Q-factor wavelet transform (TQWT). Tuning the Q-factor provides a convenient and elegant tool to naturally decompose the signal into an oscillatory and a transient component. The actual detection step relies on thresholding (i) the transient component to reveal K-complexes and (ii) the time-frequency representation of the oscillatory component to identify sleep spindles. Optimal thresholds are derived from ROC-like curves (sensitivity vs. FDR) on training sets and the performance of the method is assessed on test data sets. We assessed the performance of our method using full-night sleep EEG data we collected from 14 participants. In comparison to visual scoring (Expert 1), the proposed method detected spindles with a sensitivity of 83.18% and false discovery rate (FDR) of 39%, while K-complexes were detected with a sensitivity of 81.57% and an FDR of 29.54%. Similar performances were obtained when using a second expert as benchmark. In addition, when the TQWT and MCA steps were excluded from the pipeline the detection sensitivities dropped down to 70% for spindles and to 76.97% for K-complexes, while the FDR rose up to 43.62 and 49.09%, respectively. Finally, we also evaluated the performance of the proposed method on a set of publicly available sleep EEG recordings. Overall, the results we obtained suggest that the TQWT-MCA method may be a valuable alternative to existing spindle and K-complex detection methods. Paths for improvements and further validations with large-scale standard open-access benchmarking data sets are discussed. PMID- 26283944 TI - A pilot study of disparity vergence and near dissociated phoria in convergence insufficiency patients before vs. after vergence therapy. AB - PURPOSE: This study examined the relationship between the near dissociated phoria and disparity vergence eye movements. Convergence insufficiency (CI) patients before vergence therapy were compared to: (1) the same patients after vergence therapy; and (2) binocularly normal controls (BNC). METHODS: Sixteen subjects were studied-twelve BNC and four with CI. Measurements from the CI subjects were obtained before and after 18 h of vergence eye movement therapy. The near dissociated phoria was measured using the flashed Maddox rod technique. Vergence responses were stimulated from 4 degrees symmetrical disparity vergence step stimuli. The peak velocity of the vergence response and the magnitude of the fusion initiating component (FIC) from an independent component analysis (ICA) were calculated. A linear regression analysis was conducted studying the vergence peak velocity as a function of the near dissociated phoria where the Pearson correlation coefficient was computed. RESULTS: Before vergence therapy, the average with one standard deviation FIC magnitude of convergence responses from CI subjects was 0.29 degrees +/- 0.82 and significantly less than the FIC magnitude of 1.85 degrees +/- 0.84 for BNC (p < 0.02). A paired t-test reported that the FIC and near dissociated phoria before vergence therapy for CI subjects significantly increased to 1.49 degrees +/- 0.57 (p < 0.04) and became less exophoric to 3.5Delta +/- 1.9 exo (p < 0.02) after vergence therapy. A significant correlation (r = 0.87; p < 0.01) was observed between the near dissociated phoria and the vergence ratio of convergence peak velocity divided by divergence peak velocity. CONCLUSION: The results have clinical translational impact in understanding the mechanism by which vergence therapy may be changing the vergence system leading to a sustained reduction in visual symptoms. PMID- 26283946 TI - Audiovisual cues benefit recognition of accented speech in noise but not perceptual adaptation. AB - Perceptual adaptation allows humans to recognize different varieties of accented speech. We investigated whether perceptual adaptation to accented speech is facilitated if listeners can see a speaker's facial and mouth movements. In Study 1, participants listened to sentences in a novel accent and underwent a period of training with audiovisual or audio-only speech cues, presented in quiet or in background noise. A control group also underwent training with visual-only (speech-reading) cues. We observed no significant difference in perceptual adaptation between any of the groups. To address a number of remaining questions, we carried out a second study using a different accent, speaker and experimental design, in which participants listened to sentences in a non-native (Japanese) accent with audiovisual or audio-only cues, without separate training. Participants' eye gaze was recorded to verify that they looked at the speaker's face during audiovisual trials. Recognition accuracy was significantly better for audiovisual than for audio-only stimuli; however, no statistical difference in perceptual adaptation was observed between the two modalities. Furthermore, Bayesian analysis suggested that the data supported the null hypothesis. Our results suggest that although the availability of visual speech cues may be immediately beneficial for recognition of unfamiliar accented speech in noise, it does not improve perceptual adaptation. PMID- 26283945 TI - Basal ganglia and cortical networks for sequential ordering and rhythm of complex movements. AB - Voluntary actions require the concurrent engagement and coordinated control of complex temporal (e.g., rhythm) and ordinal motor processes. Using high resolution functional magnetic resonance imaging (fMRI) and multi-voxel pattern analysis (MVPA), we sought to determine the degree to which these complex motor processes are dissociable in basal ganglia and cortical networks. We employed three different finger-tapping tasks that differed in the demand on the sequential temporal rhythm or sequential ordering of submovements. Our results demonstrate that sequential rhythm and sequential order tasks were partially dissociable based on activation differences. The sequential rhythm task activated a widespread network centered around the supplementary motor area (SMA) and basal ganglia regions including the dorsomedial putamen and caudate nucleus, while the sequential order task preferentially activated a fronto-parietal network. There was also extensive overlap between sequential rhythm and sequential order tasks, with both tasks commonly activating bilateral premotor, supplementary motor, and superior/inferior parietal cortical regions, as well as regions of the caudate/putamen of the basal ganglia and the ventro-lateral thalamus. Importantly, within the cortical regions that were active for both complex movements, MVPA could accurately classify different patterns of activation for the sequential rhythm and sequential order tasks. In the basal ganglia, however, overlapping activation for the sequential rhythm and sequential order tasks, which was found in classic motor circuits of the putamen and ventro-lateral thalamus, could not be accurately differentiated by MVPA. Overall, our results highlight the convergent architecture of the motor system, where complex motor information that is spatially distributed in the cortex converges into a more compact representation in the basal ganglia. PMID- 26283947 TI - Multimodal imaging measures predict rearrest. AB - Rearrest has been predicted by hemodynamic activity in the anterior cingulate cortex (ACC) during error-processing (Aharoni et al., 2013). Here, we evaluate the predictive power after adding an additional imaging modality in a subsample of 45 incarcerated males from Aharoni et al. (2013). Event-related potentials (ERPs) and hemodynamic activity were collected during a Go/NoGo response inhibition task. Neural measures of error-processing were obtained from the ACC and two ERP components, the error-related negativity (ERN/Ne) and the error positivity (Pe). Measures from the Pe and ACC differentiated individuals who were and were not subsequently rearrested. Cox regression, logistic regression, and support vector machine (SVM) neuroprediction models were calculated. Each of these models proved successful in predicting rearrest and SVM provided the strongest results. Multimodal neuroprediction SVM models with out of sample cross validating accurately predicted rearrest (83.33%). Offenders with increased Pe amplitude and decreased ACC activation, suggesting abnormal error-processing, were at greatest risk of rearrest. PMID- 26283948 TI - Limb apraxia and the "affordance competition hypothesis". AB - Limb apraxia, a disorder of higher order motor control, has long been a challenge for clinical assessment and understanding (Leiguarda and Marsden, 2000). The deficits originally described in limb apraxia (Liepmann, 1920) have been classified by the nature of the errors made by the patients leading to, namely, ideational and ideomotor apraxia. The dual stream hypothesis (Goodale and Milner, 1992) has been used to explain these categories: ideational apraxia is thought to relate to a deficit in the concept of a movement (coded in the ventral stream). Patients have difficulty using objects, sequencing actions to interact with them or pantomiming their use. Ideomotor apraxia, on the other hand, is thought to arise from problems in the accurate implementation of movements within the dorsal stream. One of the limitations on understanding apraxia is the failure by the clinical literature to draw on knowledge of the factors determining actions in the environment. Here we emphasize the role of affordance. There is much recent work indicating that our responses to stimuli are strongly influenced by the actions that the objects "afford", based on their physical properties and the intentions of the actor (e.g., Tucker and Ellis, 1998). The concept of affordance, originally suggested by Gibson (1979) has been incorporated in a recent model of interactive behavior that draws from findings in non-human primates, namely the "affordance competition hypothesis" (Cisek, 2007). This postulates that interactive behavior arises by a process of competition between possible actions elicited by the environment. In this paper we argue that "affordance competition" may play a role in apraxia. We review evidence that at least some aspects of apraxia may reflect an abnormal sensitivity to competition when multiple affordances are present (Riddoch et al., 1998) and/or a poor ability to exert cognitive control over this competition when it occurs. This framework suggests a new way of conceptualizing deficits in apraxia which invites further investigations in the field. PMID- 26283950 TI - Looking for the right intention: can neuroscience benefit from the law? PMID- 26283951 TI - The effects of music listening on pain and stress in the daily life of patients with fibromyalgia syndrome. AB - Music listening is associated with both pain- and stress-reducing effects. However, the effects of music listening in daily life remain understudied, and the psycho-biological mechanisms underlying the health-beneficial effect of music listening remain unknown. We examined the effects of music listening on pain and stress in daily life in a sample of women with fibromyalgia syndrome (FMS; i.e., a condition characterized by chronic pain) and investigated whether a potentially pain-reducing effect of music listening was mediated by biological stress responsive systems. Thirty women (mean age: 50.7 +/- 9.9 years) with FMS were examined using an ecological momentary assessment design. Participants rated their current pain intensity, perceived control over pain, perceived stress level, and music listening behavior five times per day for 14 consecutive days. At each assessment, participants provided a saliva sample for the later analysis of cortisol and alpha-amylase as biomarkers of stress-responsive systems. Hierarchical linear modeling revealed that music listening increased perceived control over pain, especially when the music was positive in valence and when it was listened to for the reason of 'activation' or 'relaxation'. In contrast, no effects on perceived pain intensity were observed. The effects of music listening on perceived control over pain were not mediated by biomarkers of stress responsive systems. Music listening in daily life improved perceived control over pain in female FMS patients. Clinicians using music therapy should become aware of the potential adjuvant role of music listening in daily life, which has the potential to improve symptom control in chronic pain patients. In order to study the role of underlying biological mechanisms, it might be necessary to use more intensive engagement with music (i.e., collective singing or music-making) rather than mere music listening. PMID- 26283949 TI - Role of the parahippocampal cortex in memory for the configuration but not the identity of objects: converging evidence from patients with selective thermal lesions and fMRI. AB - The parahippocampal cortex and hippocampus are brain structures known to be involved in memory. However, the unique contribution of the parahippocampal cortex remains unclear. The current study investigates memory for object identity and memory of the configuration of objects in patients with small thermo coagulation lesions to the hippocampus or the parahippocampal cortex. Results showed that in contrast to control participants and patients with damage to the hippocampus leaving the parahippocampal cortex intact, patients with lesions that included the right parahippocampal cortex (RPH) were severely impaired on a task that required learning the spatial configuration of objects on a computer screen; these patients, however, were not impaired at learning the identity of objects. Conversely, we found that patients with lesions to the right hippocampus (RH) or left hippocampus (LH), sparing the parahippocampal cortex, performed just as well as the control participants. Furthermore, they were not impaired on the object identity task. In the functional Magnetic Resonance Imaging (fMRI) experiment, healthy young adults performed the same tasks. Consistent with the findings of the lesion study, the fMRI results showed significant activity in the RPH in the memory for the spatial configuration condition, but not memory for object identity. Furthermore, the pattern of fMRI activity measured in the baseline control conditions decreased specifically in the parahippocampal cortex as a result of the experimental task, providing evidence for task specific repetition suppression. In summary, while our previous studies demonstrated that the hippocampus is critical to the construction of a cognitive map, both the lesion and fMRI studies have shown an involvement of the RPH for learning spatial configurations of objects but not object identity, and that this takes place independent of the hippocampus. PMID- 26283952 TI - Effects of Transcranial Direct Current Stimulation on the Recognition of Bodily Emotions from Point-Light Displays. AB - Perceiving human motion, recognizing actions, and interpreting emotional body language are tasks we perform daily and which are supported by a network of brain areas including the human posterior superior temporal sulcus (pSTS). Here, we applied transcranial direct current stimulation (tDCS) with anodal (excitatory) or cathodal (inhibitory) electrodes mounted over right pSTS (target) and orbito frontal cortex (reference) while healthy participants performed a bodily emotion recognition task using biological motion point-light displays (PLDs). Performance (accuracy and reaction times) was also assessed on a control task which was matched to the emotion recognition task in terms of cognitive and motor demands. Each subject participated in two experimental sessions, receiving either anodal or cathodal stimulation, which were separated by one week to avoid residual effects of previous stimulations. Overall, tDCS brain stimulation did not affect the recognition of emotional states from PLDs. However, when emotions with a negative or positive-neutral emotional valence were analyzed separately, effects of stimulation were shown for recognizing emotions with a negative emotional valence (sadness and anger), indicating increased recognition performance when receiving anodal (excitatory) stimulation compared to cathodal (inhibitory) stimulation over pSTS. No stimulation effects were shown for the recognition of emotions with positive-neutral emotional valences. These findings extend previous studies showing structure-function relationships between STS and biological motion processing from PLDs and provide indications that stimulation effects may be modulated by the emotional valence of the stimuli. PMID- 26283953 TI - The neuroaesthetics of prose fiction: pitfalls, parameters and prospects. AB - There is a paucity of neuroaesthetic studies on prose fiction. This is in contrast to the very many impressive studies that have been conducted in recent times on the neuroaesthetics of sister arts such as painting, music and dance. Why might this be the case, what are its causes and, of greatest importance, how can it best be resolved? In this article, the pitfalls, parameters and prospects of a neuroaesthetics of prose fiction will be explored. The article itself is part critical review, part methodological proposal and part opinion paper. Its aim is simple: to stimulate, excite and energize thinking in the discipline as to how prose fiction might be fully integrated in the canon of neuroaesthetics and to point to opportunities where neuroimaging studies on literary discourse processing might be conducted in collaborative work bringing humanists and scientists together. PMID- 26283954 TI - Modeling the calcium spike as a threshold triggered fixed waveform for synchronous inputs in the fluctuation regime. AB - Modeling the layer 5 pyramidal neuron as a system of three connected isopotential compartments, the soma, proximal, and distal compartment, with calcium spike dynamics in the distal compartment following first order kinetics, we are able to reproduce in-vitro experimental results which demonstrate the involvement of calcium spikes in action potentials generation. To explore how calcium spikes affect the neuronal output in-vivo, we emulate in-vivo like conditions by embedding the neuron model in a regime of low background fluctuations with occasional large synchronous inputs. In such a regime, a full calcium spike is only triggered by the synchronous events in a threshold like manner and has a stereotypical waveform. Hence, in such a regime, we are able to replace the calcium dynamics with a simpler threshold triggered current of fixed waveform, which is amenable to analytical treatment. We obtain analytically the mean somatic membrane potential excursion due to a calcium spike being triggered while in the fluctuating regime. Our analytical form that accounts for the covariance between conductances and the membrane potential shows a better agreement with simulation results than a naive first order approximation. PMID- 26283955 TI - Mechanisms for multiple activity modes of VTA dopamine neurons. AB - Midbrain ventral segmental area (VTA) dopaminergic neurons send numerous projections to cortical and sub-cortical areas, and diffusely release dopamine (DA) to their targets. DA neurons display a range of activity modes that vary in frequency and degree of burst firing. Importantly, DA neuronal bursting is associated with a significantly greater degree of DA release than an equivalent tonic activity pattern. Here, we introduce a single compartmental, conductance based computational model for DA cell activity that captures the behavior of DA neuronal dynamics and examine the multiple factors that underlie DA firing modes: the strength of the SK conductance, the amount of drive, and GABA inhibition. Our results suggest that neurons with low SK conductance fire in a fast firing mode, are correlated with burst firing, and require higher levels of applied current before undergoing depolarization block. We go on to consider the role of GABAergic inhibition on an ensemble of dynamical classes of DA neurons and find that strong GABA inhibition suppresses burst firing. Our studies suggest differences in the distribution of the SK conductance and GABA inhibition levels may indicate subclasses of DA neurons within the VTA. We further identify, that by considering alternate potassium dynamics, the dynamics display burst patterns that terminate via depolarization block, akin to those observed in vivo in VTA DA neurons and in substantia nigra pars compacta (SNc) DA cell preparations under apamin application. In addition, we consider the generation of transient burst firing events that are NMDA-initiated or elicited by a sudden decrease of GABA inhibition, that is, disinhibition. PMID- 26283956 TI - Synaptic dynamics and neuronal network connectivity are reflected in the distribution of times in Up states. AB - The dynamics of neuronal networks connected by synaptic dynamics can sustain long periods of depolarization that can last for hundreds of milliseconds such as Up states recorded during sleep or anesthesia. Yet the underlying mechanism driving these periods remain unclear. We show here within a mean-field model that the residence time of the neuronal membrane potential in cortical Up states does not follow a Poissonian law, but presents several peaks. Furthermore, the present modeling approach allows extracting some information about the neuronal network connectivity from the time distribution histogram. Based on a synaptic-depression model, we find that these peaks, that can be observed in histograms of patch clamp recordings are not artifacts of electrophysiological measurements, but rather are an inherent property of the network dynamics. Analysis of the equations reveals a stable focus located close to the unstable limit cycle, delimiting a region that defines the Up state. The model further shows that the peaks observed in the Up state time distribution are due to winding around the focus before escaping from the basin of attraction. Finally, we use in vivo recordings of intracellular membrane potential and we recover from the peak distribution, some information about the network connectivity. We conclude that it is possible to recover the network connectivity from the distribution of times that the neuronal membrane voltage spends in Up states. PMID- 26283957 TI - ANNarchy: a code generation approach to neural simulations on parallel hardware. AB - Many modern neural simulators focus on the simulation of networks of spiking neurons on parallel hardware. Another important framework in computational neuroscience, rate-coded neural networks, is mostly difficult or impossible to implement using these simulators. We present here the ANNarchy (Artificial Neural Networks architect) neural simulator, which allows to easily define and simulate rate-coded and spiking networks, as well as combinations of both. The interface in Python has been designed to be close to the PyNN interface, while the definition of neuron and synapse models can be specified using an equation oriented mathematical description similar to the Brian neural simulator. This information is used to generate C++ code that will efficiently perform the simulation on the chosen parallel hardware (multi-core system or graphical processing unit). Several numerical methods are available to transform ordinary differential equations into an efficient C++code. We compare the parallel performance of the simulator to existing solutions. PMID- 26283959 TI - Direct costs of dementia in nursing homes. AB - Dementia represents an economical burden to societies nowadays. Total dementia expenses are calculated by the sum of direct and indirect costs. Through the stages of the diseases, as the patients may require institutionalization or a formal caregiver, the direct costs tend to increase. This study aims to analyze the direct costs of dementia in Portuguese nursing homes in 2012, compare the spending between seniors with and without dementia, and propose a predictive costs model. The expenses analysis was based on (1) the use of emergency rooms and doctor's appointments, either in public or private institutions; (2) days of hospitalization; (3) medication; (4) social services use; (5) the need for technical support; and (6) the utilization of rehabilitation services. The sample was composed of 72 people, half with dementia and half without. The average annual expense of a patient with dementia was ?15,287 thousand, while the cost of a patient without dementia was about ?12,289 thousand. The variables "ability to make yourself understood," "self-performance: getting dressed" and "thyroid disorders" were found to be statistically significant in predicting the expenses' increase. In nursing homes, in 2012, the costs per patient with dementia were 1, 2 times higher than per patient without dementia. PMID- 26283958 TI - Neuroligin 1 modulates striatal glutamatergic neurotransmission in a pathway and NMDAR subunit-specific manner. AB - Together with its presynaptic partner Neurexin 1 (Nxn1), Neuroligin 1 (NL1) participates in synapse specification and synapse maintenance. We and others have shown that NL1 can also modulate glutamatergic synaptic function in the central nervous system of rodent models. These molecular/cellular changes can translate into altered animal behaviors that are thought to be analogous to symptomatology of neuropsychiatric disorders. For example, in dorsal striatum of NL1 deletion mice, we previously reported that the ratio N-methyl-D-aspartate receptor (NMDAR) mediated synaptic currents to alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionate receptor (AMPAR) mediated synaptic currents (NMDA/AMPA) is reduced in medium spiny neuron (MSNs). Importantly, this reduction in NMDA/AMPA ratio correlated with increased repetitive grooming. The striatum is the input nucleus of the basal ganglia (BG). Classical models of this circuitry imply that there are two principal pathways that render distinct and somewhat opposite striatal outputs critical to the function of these nuclei in modulating motor behavior. Thus, we set out to better characterize the effects of NL1 deletion on direct and indirect pathways of the dorsal striatum by genetically labeling MSNs participating in the direct and indirect pathways. We demonstrate that a decrease in NMDAR-mediated currents is limited to MSNs of the direct pathway. Furthermore, the decrease in NMDAR-mediated currents is largely due to a reduction in function of NMDARs containing the GluN2A subunit. In contrast, indirect pathway MSNs in NL1 knockout (KO) mice showed a reduction in the frequency of miniature excitatory neurotransmission not observed in the direct pathway. Thus, NL1 deletion differentially affects direct and indirect pathway MSNs in dorsal striatum. These findings have potential implications for striatal function in NL1 KO mice. PMID- 26283960 TI - Electroacupuncture Reduces Abeta Production and BACE1 Expression in SAMP8 Mice. AB - Electroacupuncture (EA) has been reported to have beneficial effects on Alzheimer's disease (AD). BACE1 (beta-site amyloid precursor protein-cleaving enzyme 1) is involved in the abnormal production of amyloid-beta plaque (Abeta), a hallmark of AD pathophysiology. Thus, the present study investigated the effects of EA on memory impairment, Abeta production, and BACE1 expression in senescence-accelerated mouse prone 8 (SAMP8) mice. We found that EA improved spatial learning and memory impairment of SAMP8 mice. Furthermore, EA attenuated Abeta production and repressed the expression of BACE1 in the hippocampus of SAMP8 mice. Taken together, our results suggest that EA could have a potential therapeutic application in AD and that BACE1 may be an important target of EA in the treatment of AD. PMID- 26283961 TI - A hemodynamic model to guide blood pressure control during deliberate hypotension with sodium nitroprusside in children. AB - Sodium nitroprusside (SNP) has been widely used to control blood pressure in infants and children. The goals of this analysis were to develop models that describe the hemodynamic response to SNP dosing in pediatric patients; examine sources of variation in dose-response, defining age, and size dependencies; and determine vulnerable populations or patient subtypes that may elicit dosing modifications. A multi-center, randomized, double-blinded, parallel-group, dose ranging, effect-controlled study, followed by an open-label dose titration of an intravenous infusion of SNP was undertaken in 203 pediatric subjects, who required deliberate hypotension or controlled normotension during anesthesia. A total of 3464 MAP measurements collected from 202 patients during the study's blinded phase, including baseline measurements up to 6 min prior to the blinded were available for analysis. A population K-PD model was developed with a one compartment model assumed for SNP. Size differences in CL and V of the effect compartment were described using theory-based allometry. An inhibitory sigmoidal Emax model was used to describe the effect of SNP. A power function of age was used to describe age-related differences in baseline MAP. A mixture model of two groups with low and high EC50 was used to explain variability in MAP response. Change in MAP was characterized by a linear disease progression slope during the blinded phase. In the final population model, CL and V increased with weight, and baseline MAP increased with age. The effect compartment half-life of SNP was 13.4 min. The infusion rate producing 50% of Emax (ER50) at steady state for high EC50, was 0.34 MUg/kg/min and for low EC50 0.103 MUg/kg/min. The K-PD model well describes initial dosing of SNP under controlled circumstances; model-based dosing guidance agrees with current practice. An initial titration strategy supported via algorithm-based feedback should improve maintenance of target MAP. PMID- 26283963 TI - Targeting brain tumor cAMP: the case for sex-specific therapeutics. AB - A relationship between cyclic adenosine 3', 5'-monophosphate (cAMP) levels and brain tumor biology has been evident for nearly as long as cAMP and its synthetase, adenylate cyclase (ADCY) have been known. The importance of the pathway in brain tumorigenesis has been demonstrated in vitro and in multiple animal models. Recently, we provided human validation for a cooperating oncogenic role for cAMP in brain tumorigenesis when we found that SNPs in ADCY8 were correlated with glioma (brain tumor) risk in individuals with Neurofibromatosis type 1 (NF1). Together, these studies provide a strong rationale for targeting cAMP in brain tumor therapy. However, the cAMP pathway is well-known to be sexually dimorphic, and SNPs in ADCY8 affected glioma risk in a sex-specific fashion, elevating the risk for females while protecting males. The cAMP pathway can be targeted at multiple levels in the regulation of its synthesis and degradation. Sex differences in response to drugs that target cAMP regulators indicate that successful targeting of the cAMP pathway for brain tumor patients is likely to require matching specific mechanisms of drug action with patient sex. PMID- 26283965 TI - Nutrition, a health technology that deserves increasing interest among HTA doers. A systematic review. AB - The increasing interest for evaluating indirect consequences of health care interventions and their interaction with patients' behavior have put the focus on health promotion interventions including nutrition and the need to measure and evaluate them. OBJECTIVE: In this review we have aimed to analyze current status of written and published reports on nutrition and nutrition interventions by HTA doers, how assessment has been approached and which metrics and designs have been proposed. METHODS: For that purpose, we searched the Center for Reviews and Dissemination databases (CRD) comprising the International Network of Agencies for HTA database (INAHTA), the database of effects (DARE) and the National Health Service Economic Evaluation Database (NHS EED). The words used include nutrition and nutrition interventions and there was no limit on data coverage. We complemented the search by manually seek for further reports on INAHTA's agencies webpages. We extracted the reports for their classification and analysis. RESULTS: We found 82 reports from different sources and after applying inclusion and exclusion criteria, we finally included 42. All the reports correspond to High income Countries (HiC) including agencies from Europe, North America and Oceania. The agencies or programs most represented correspond to the NIHR (UK) and AHRQ (USA). There were general reports around the role of functional foods and specific reports on the impact of establishing nutrition specific strategies in hospitals. 6 out of 42 analyzed the economic consequences of nutrition interventions and 4 reports were related to the methodologies used or the appliance of systematic review methods to the field of nutrition. CONCLUSIONS: the reports included correspond to HiC while those HTA agencies established in Low and Middle Income countries (LMiC) have no reported or written activities on the role of nutrition and nutrition interventions. Retrieved reports written by HTA doers/producers confirm the use and utility of systematic reviews and economic analysis methods and its applicability for nutrition interventions. However, some measurements such as Quality Adjusted Life Years (QALY) need to be refined to better reflect the impact of these interventions. PMID- 26283962 TI - Voltage-gated sodium channels and cancer: is excitability their primary role? AB - Voltage-gated sodium channels (NaV) are molecular characteristics of excitable cells. Their activation, triggered by membrane depolarization, generates transient sodium currents that initiate action potentials in neurons and muscle cells. Sodium currents were discovered by Hodgkin and Huxley using the voltage clamp technique and reported in their landmark series of papers in 1952. It was only in the 1980's that sodium channel proteins from excitable membranes were molecularly characterized by Catterall and his collaborators. Non-excitable cells can also express NaV channels in physiological conditions as well as in pathological conditions. These NaV channels can sustain biological roles that are not related to the generation of action potentials. Interestingly, it is likely that the abnormal expression of NaV in pathological tissues can reflect the re expression of a fetal phenotype. This is especially true in epithelial cancer cells for which these channels have been identified and sodium currents recorded, while it was not the case for cells from the cognate normal tissues. In cancers, the functional activity of NaV appeared to be involved in regulating the proliferative, migrative, and invasive properties of cells. This review is aimed at addressing the non-excitable roles of NaV channels with a specific emphasis in the regulation of cancer cell biology. PMID- 26283964 TI - Urokinase receptor and resistance to targeted anticancer agents. AB - The urokinase receptor (uPAR) is a GPI-anchored membrane protein, which regulates protease activity at the cell surface and, in collaboration with a system of co receptors, triggers cell-signaling and regulates gene expression within the cell. In normal tissues, uPAR gene expression is limited; however, in cancer, uPAR is frequently over-expressed and the gene may be amplified. Hypoxia, which often develops in tumors, further increases uPAR expression by cancer cells. uPAR initiated cell-signaling promotes cancer cell migration, invasion, metastasis, epithelial-mesenchymal transition, stem cell-like properties, survival, and release from states of dormancy. Newly emerging data suggest that the pro survival cell-signaling activity of uPAR may allow cancer cells to "escape" from the cytotoxic effects of targeted anticancer drugs. Herein, we review the molecular properties of uPAR that are responsible for its activity in cancer cells and its ability to counteract the activity of anticancer drugs. PMID- 26283966 TI - Computational polypharmacology comes of age. PMID- 26283967 TI - Therapeutic strategies for anchored kinases and phosphatases: exploiting short linear motifs and intrinsic disorder. AB - Phosphorylation events that occur in response to the second messenger cAMP are controlled spatially and temporally by protein kinase A (PKA) interacting with A kinase anchoring proteins (AKAPs). Recent advances in understanding the structural basis for this interaction have reinforced the hypothesis that AKAPs create spatially constrained signaling microdomains. This has led to the realization that the PKA/AKAP interface is a potential drug target for modulating a plethora of cell-signaling events. Pharmacological disruption of kinase-AKAP interactions has previously been explored for disease treatment and remains an interesting area of research. However, disrupting or enhancing the association of phosphatases with AKAPs is a therapeutic concept of equal promise, particularly since they oppose the actions of many anchored kinases. Accordingly, numerous AKAPs bind phosphatases such as protein phosphatase 1 (PP1), calcineurin (PP2B), and PP2A. These multimodal signaling hubs are equally able to control the addition of phosphate groups onto target substrates, as well as the removal of these phosphate groups. In this review, we describe recent advances in structural analysis of kinase and phosphatase interactions with AKAPs, and suggest future possibilities for targeting these interactions for therapeutic benefit. PMID- 26283968 TI - It takes two-coincidence coding within the dual olfactory pathway of the honeybee. AB - To rapidly process biologically relevant stimuli, sensory systems have developed a broad variety of coding mechanisms like parallel processing and coincidence detection. Parallel processing (e.g., in the visual system), increases both computational capacity and processing speed by simultaneously coding different aspects of the same stimulus. Coincidence detection is an efficient way to integrate information from different sources. Coincidence has been shown to promote associative learning and memory or stimulus feature detection (e.g., in auditory delay lines). Within the dual olfactory pathway of the honeybee both of these mechanisms might be implemented by uniglomerular projection neurons (PNs) that transfer information from the primary olfactory centers, the antennal lobe (AL), to a multimodal integration center, the mushroom body (MB). PNs from anatomically distinct tracts respond to the same stimulus space, but have different physiological properties, characteristics that are prerequisites for parallel processing of different stimulus aspects. However, the PN pathways also display mirror-imaged like anatomical trajectories that resemble neuronal coincidence detectors as known from auditory delay lines. To investigate temporal processing of olfactory information, we recorded PN odor responses simultaneously from both tracts and measured coincident activity of PNs within and between tracts. Our results show that coincidence levels are different within each of the two tracts. Coincidence also occurs between tracts, but to a minor extent compared to coincidence within tracts. Taken together our findings support the relevance of spike timing in coding of olfactory information (temporal code). PMID- 26283969 TI - The role of miRNAs in stress-responsive hepatic stellate cells during liver fibrosis. AB - The progression of liver fibrosis and cirrhosis is associated with the persistence of an injury causing agent, leading to changes in the extracellular environment and a disruption of the cellular homeostasis of liver resident cells. Recruitment of inflammatory cells, apoptosis of hepatocytes, and changes in liver microvasculature are some examples of changing cellular environment that lead to the induction of stress responses in nearby cells. During liver fibrosis, the major stresses include hypoxia, oxidative stress, and endoplasmic reticulum stress. When hepatic stellate cells (HSCs) are subjected to such stress, they modulate fibrosis progression by induction of their activation toward a myofibroblastic phenotype, or by undergoing apoptosis, and thus helping fibrosis resolution. It is widely accepted that microRNAs are import regulators of gene expression, both during normal cellular homeostasis, as well as in pathologic conditions. MicroRNAs are short RNA sequences that regulate the gene expression by mRNA destabilization and inhibition of mRNA translation. Specific microRNAs have been identified to play a role in the activation process of HSCs on the one hand and in stress-responsive pathways on the other hand in other cell types (Table 2). However, so far there are no reports for the involvement of miRNAs in the different stress responses linked to HSC activation. Here, we review briefly the major stress response pathways and propose several miRNAs to be regulated by these stress responsive pathways in activating HSCs, and discuss their potential specific pro-or anti-fibrotic characteristics. PMID- 26283970 TI - On the mechanism by which dietary nitrate improves human skeletal muscle function. AB - Inorganic nitrate is present at high levels in beetroot and celery, and in green leafy vegetables such as spinach and lettuce. Though long believed inert, nitrate can be reduced to nitrite in the human mouth and, further, under hypoxia and/or low pH, to nitric oxide. Dietary nitrate has thus been associated favorably with nitric-oxide-regulated processes including blood flow and energy metabolism. Indeed, the therapeutic potential of dietary nitrate in cardiovascular disease and metabolic syndrome-both aging-related medical disorders-has attracted considerable recent research interest. We and others have shown that dietary nitrate supplementation lowers the oxygen cost of human exercise, as less respiratory activity appears to be required for a set rate of skeletal muscle work. This striking observation predicts that nitrate benefits the energy metabolism of human muscle, increasing the efficiency of either mitochondrial ATP synthesis and/or of cellular ATP-consuming processes. In this mini-review, we evaluate experimental support for the dietary nitrate effects on muscle bioenergetics and we critically discuss the likelihood of nitric oxide as the molecular mediator of such effects. PMID- 26283971 TI - Hypoxanthine-guanine phosphoribosyltransferase and inosine 5'-monophosphate dehydrogenase activities in three mammalian species: aquatic (Mirounga angustirostris), semi-aquatic (Lontra longicaudis annectens) and terrestrial (Sus scrofa). AB - Aquatic and semiaquatic mammals have the capacity of breath hold (apnea) diving. Northern elephant seals (Mirounga angustirostris) have the ability to perform deep and long duration dives; during a routine dive, adults can hold their breath for 25 min. Neotropical river otters (Lontra longicaudis annectens) can hold their breath for about 30 s. Such periods of apnea may result in reduced oxygen concentration (hypoxia) and reduced blood supply (ischemia) to tissues. Production of adenosine 5'-triphosphate (ATP) requires oxygen, and most mammalian species, like the domestic pig (Sus scrofa), are not adapted to tolerate hypoxia and ischemia, conditions that result in ATP degradation. The objective of this study was to explore the differences in purine synthesis and recycling in erythrocytes and plasma of three mammalian species adapted to different environments: aquatic (northern elephant seal) (n = 11), semiaquatic (neotropical river otter) (n = 4), and terrestrial (domestic pig) (n = 11). Enzymatic activity of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) was determined by spectrophotometry, and activity of inosine 5'-monophosphate dehydrogenase (IMPDH) and the concentration of hypoxanthine (HX), inosine 5'-monophosphate (IMP), adenosine 5'-monophosphate (AMP), adenosine 5'-diphosphate (ADP), ATP, guanosine 5'-diphosphate (GDP), guanosine 5'-triphosphate (GTP), and xanthosine 5' monophosphate (XMP) were determined by high-performance liquid chromatography (HPLC). The activities of HGPRT and IMPDH and the concentration of HX, IMP, AMP, ADP, ATP, GTP, and XMP in erythrocytes of domestic pigs were higher than in erythrocytes of northern elephant seals and river otters. These results suggest that under basal conditions (no diving, sleep apnea or exercise), aquatic, and semiaquatic mammals have less purine mobilization than their terrestrial counterparts. PMID- 26283972 TI - Community-Based Global Health Program for Maltreated Children and Adolescents in Brazil: The Equilibrium Program. AB - The maltreatment of children and adolescents is a global public health problem that affects high- and low-middle income countries ("LMICs"). In the United States, around 1.2 million children suffer from abuse, while in LMICs, such as Brazil, these rates are much higher (an estimated 28 million children). Exposition to early environmental stress has been associated with suboptimal physical and brain development, persistent cognitive impairment, and behavioral problems. Studies have reported that children exposed to maltreatment are at high risk of behavioral problems, learning disabilities, communication and psychiatric disorders, and general clinical conditions, such as obesity and systemic inflammation later in life. The aim of this paper is to describe The Equilibrium Program ("TEP"), a community-based global health program implemented in Sao Paulo, Brazil to serve traumatized and neglected children and adolescents. We will describe and discuss TEP's implementation, highlighting its innovation aspects, research projects developed within the program as well as its population profile. Finally, we will discuss TEP's social impact, challenges, and limitations. The program's goal is to promote the social and family reintegration of maltreated children and adolescents through an interdisciplinary intervention program that provides multi-dimensional bio-psycho-social treatment integrated with the diverse services needed to meet the unique demands of this population. The program's cost effectiveness is being evaluated to support the development of more effective treatments and to expand similar programs in other areas of Brazil. Policy makers should encourage early evidence-based interventions for disadvantaged children to promote healthier psychosocial environments and provide them opportunities to become healthy and productive adults. This approach has already shown itself to be a cost-effective strategy to prevent disease and promote health. PMID- 26283973 TI - Toward a Deeper Understanding of the Genetics of Bipolar Disorder. AB - Bipolar disorder is a common, complex psychiatric disorder characterized by mania and depression. The disease aggregates in families, but despite much effort, it has been difficult to delineate the basic genetic model or identify specific genetic risk factors. Not only single gene Mendelian transmission and common variant hypotheses but also multivariate threshold models and oligogenic quasi Mendelian modes of inheritance have dominated the discussion at times. Almost complete sequence information of the human genome and falling sequencing costs now offer the opportunity to test these models in families in which the disorder is transmitted over several generations. Exome-wide sequencing studies have revealed an astonishing number of rare and potentially damaging mutations in brain-expressed genes that could have contributed to the disease manifestation. However, the statistical analysis of these data has been challenging, because genetic risk factors displayed a high degree of dissimilarity across families. This scenario is not unique to bipolar disorder, but similar results have also been found in schizophrenia, a potentially related psychiatric disorder. Recently, our group has published data which supported an oligogenic genetic model of transmission in a family with bipolar disorder. In this family, three affected siblings shared rare, damaging mutations in multiple genes, which were linked to stress response pathways. These pathways are also the target for drugs frequently used to treat bipolar disorder. This article discusses these findings in the context of previously proclaimed disease models and suggests future research directions, including biological confirmation and phenotype stratification as an approach to disease heterogeneity. PMID- 26283974 TI - Structural MRI Differences between Patients with and without First Rank Symptoms: A Delusion? AB - OBJECTIVE: It has been suggested that specific psychotic symptom clusters may be explained by patterns of biological abnormalities. The presence of first rank symptoms (FRS) has been associated with cognitive abnormalities, e.g., deficits in self-monitoring or in the experience of agency, suggesting that a specific network of neural abnormalities might underlie FRS. Here, we investigate differences in cortical and subcortical brain volume between patients with and without FRS. METHODS: Three independent patient samples (referred to as A, B, and C) with different mean ages and in different illness stages were included, leading to a total of 348 patients within the schizophrenia-spectrum. All underwent magnetic resonance imaging of the brain. In addition, the presence of FRS was established using a diagnostic interview. Patients with (FRS+, A: n = 63, B: n = 129, and C: n = 96) and without FRS (FRS-, A: n = 35, B: n = 17, and C: n = 8) were compared on global and local cortical volumes as well as subcortical volumes, using a whole brain (cerebrum) approach. RESULTS: Nucleus accumbens volume was significantly smaller in FRS+ as compared with FRS- in sample A (p < 0.005). Furthermore, FRS+ showed a smaller volume of the pars-opercularis relative to FRS- in sample B (p < 0.001). No further significant differences were found in cortical and subcortical volumes between FRS+ and FRS- in either one of the three samples after correction for multiple comparison. CONCLUSION: Brain volume differences between patients with and without FRS are, when present, subtle, and not consistent between three independent samples. Brain abnormalities related to FRS may be too subtle to become visible through structural brain imaging. PMID- 26283975 TI - A Systematic Review of the Evidence for Impaired Cognitive Theory of Mind in Maltreated Children. AB - Compared to the large number of studies exploring difficulties in emotion recognition in maltreated children, few (N = 12) have explored the cognitive aspect of theory of mind (ToM), i.e., the ability to understand others' thoughts and intentions. A systematic review of these studies shows inconsistent results regarding cognitive ToM tasks. Youths with a history of maltreatment are more likely to fail at false-belief tasks (N = 2). However, results are less conclusive regarding other tasks (perspective-taking tasks, N = 4; and hostile attribution tasks, N = 7). Additionally, only one study controlled for potential psychopathology. Measures of psychopathology and other cognitive abilities, in addition to ToM, are required to establish a specific association between maltreatment and the cognitive dimension of ToM. PMID- 26283977 TI - Collapsing factors in multitrait-multimethod models: examining consequences of a mismatch between measurement design and model. AB - Models of confirmatory factor analysis (CFA) are frequently applied to examine the convergent validity of scores obtained from multiple raters or methods in so called multitrait-multimethod (MTMM) investigations. Many applications of CFA MTMM and similarly structured models result in solutions in which at least one method (or specific) factor shows non-significant loading or variance estimates. Eid et al. (2008) distinguished between MTMM measurement designs with interchangeable (randomly selected) vs. structurally different (fixed) methods and showed that each type of measurement design implies specific CFA-MTMM measurement models. In the current study, we hypothesized that some of the problems that are commonly seen in applications of CFA-MTMM models may be due to a mismatch between the underlying measurement design and fitted models. Using simulations, we found that models with M method factors (where M is the total number of methods) and unconstrained loadings led to a higher proportion of solutions in which at least one method factor became empirically unstable when these models were fit to data generated from structurally different methods. The simulations also revealed that commonly used model goodness-of-fit criteria frequently failed to identify incorrectly specified CFA-MTMM models. We discuss implications of these findings for other complex CFA models in which similar issues occur, including nested (bifactor) and latent state-trait models. PMID- 26283976 TI - Comprehension and computation in Bayesian problem solving. AB - Humans have long been characterized as poor probabilistic reasoners when presented with explicit numerical information. Bayesian word problems provide a well-known example of this, where even highly educated and cognitively skilled individuals fail to adhere to mathematical norms. It is widely agreed that natural frequencies can facilitate Bayesian inferences relative to normalized formats (e.g., probabilities, percentages), both by clarifying logical set-subset relations and by simplifying numerical calculations. Nevertheless, between-study performance on "transparent" Bayesian problems varies widely, and generally remains rather unimpressive. We suggest there has been an over-focus on this representational facilitator (i.e., transparent problem structures) at the expense of the specific logical and numerical processing requirements and the corresponding individual abilities and skills necessary for providing Bayesian like output given specific verbal and numerical input. We further suggest that understanding this task-individual pair could benefit from considerations from the literature on mathematical cognition, which emphasizes text comprehension and problem solving, along with contributions of online executive working memory, metacognitive regulation, and relevant stored knowledge and skills. We conclude by offering avenues for future research aimed at identifying the stages in problem solving at which correct vs. incorrect reasoners depart, and how individual differences might influence this time point. PMID- 26283978 TI - Hallucinations and related concepts-their conceptual background. AB - Prior to the seventeenth century, the experiences we now name hallucinations were valued within a cultural context, they could bring meaning to the subject or the world. From mid-seventeenth to eighteenth centuries, they acquire a medical quality in mental and organic illnesses. However, the term was only fully integrated in psychiatry by Esquirol in the eighteenth-nineteenth centuries. By then, a controversy begins on whether hallucinations have a perceptual or intellectual origin. Esquirol favors the intellectual origin, describing them as an involuntary exercise of memory and imagination. By the twentieth century, some authors maintain that hallucinations are a form of delusion (Ey), while others describe them as a change in perception (Jaspers, Fish). More integrated perspectives like those proposed by Alonso Fernandez and Luque, highlights the heterogeneity of hallucinations and the multiplicity of their types and causes. The terms pseudohallucination, illusion, and hallucinosis are grafted into the concept of hallucination. Since its introduction the term pseudohallucination has been used with different meanings. The major characteristics that we found associated with pseudohallucinations were "lack of objectivity" and "presence of insight" (differing from hallucinations). Illusions are unanimously taken as distortions of real objects. Hallucinosis, first described in the context of alcohol consumption, is generally considered egodystonic, in which insight is preserved. These and other controversial aspects regarding the evolution of the term hallucination and all its derivative concepts are discussed in this paper. PMID- 26283979 TI - Quantum-like model of unconscious-conscious dynamics. AB - We present a quantum-like model of sensation-perception dynamics (originated in Helmholtz theory of unconscious inference) based on the theory of quantum apparatuses and instruments. We illustrate our approach with the model of bistable perception of a particular ambiguous figure, the Schroder stair. This is a concrete model for unconscious and conscious processing of information and their interaction. The starting point of our quantum-like journey was the observation that perception dynamics is essentially contextual which implies impossibility of (straightforward) embedding of experimental statistical data in the classical (Kolmogorov, 1933) framework of probability theory. This motivates application of nonclassical probabilistic schemes. And the quantum formalism provides a variety of the well-approved and mathematically elegant probabilistic schemes to handle results of measurements. The theory of quantum apparatuses and instruments is the most general quantum scheme describing measurements and it is natural to explore it to model the sensation-perception dynamics. In particular, this theory provides the scheme of indirect quantum measurements which we apply to model unconscious inference leading to transition from sensations to perceptions. PMID- 26283980 TI - Eleven-month-old infants infer differences in the hardness of object surfaces from observation of penetration events. AB - Previous studies have shown different developmental trajectories for object recognition of solid and non-solid objects. However, there is no evidence as to whether infants have expectations regarding certain attributes of objects, such as surface hardness, in the absence of tactile information. In the present study, we examined infants' perception of the hardness of object surfaces from visually presented penetration events using the familiarization-novelty preference procedure. Experiment 1 showed that by 11 months old infants distinguished a relatively soft surface from a crusty surface based on changes in the velocity of a moving object as the moving object penetrated the surface of the target object. Experiment 2 ruled out the possibility that infants were merely sensitive to differences in the velocity changes in the stimuli. PMID- 26283981 TI - How does susceptibility to proactive interference relate to speech recognition in aided and unaided conditions? AB - Proactive interference (PI) is the capacity to resist interference to the acquisition of new memories from information stored in the long-term memory. Previous research has shown that PI correlates significantly with the speech-in noise recognition scores of younger adults with normal hearing. In this study, we report the results of an experiment designed to investigate the extent to which tests of visual PI relate to the speech-in-noise recognition scores of older adults with hearing loss, in aided and unaided conditions. The results suggest that measures of PI correlate significantly with speech-in-noise recognition only in the unaided condition. Furthermore the relation between PI and speech-in-noise recognition differs to that observed in younger listeners without hearing loss. The findings suggest that the relation between PI tests and the speech-in-noise recognition scores of older adults with hearing loss relates to capability of the test to index cognitive flexibility. PMID- 26283982 TI - Characteristic visuomotor influences on eye-movement patterns to faces and other high level stimuli. AB - Eye-movement patterns are often utilized in studies of visual perception as indices of the specific information extracted to efficiently process a given stimulus during a given task. Our prior work, however, revealed that not only the stimulus and task influence eye-movements, but that visuomotor (start position) factors also robustly and characteristically influence eye-movement patterns to faces (Arizpe et al., 2012). Here we manipulated lateral starting side and distance from the midline of face and line-symmetrical control (butterfly) stimuli in order to further investigate the nature and generality of such visuomotor influences. First we found that increasing starting distance from midline (4 degrees , 8 degrees , 12 degrees , and 16 degrees visual angle) strongly and proportionately increased the distance of the first ordinal fixation from midline. We did not find influences of starting distance on subsequent fixations, however, suggesting that eye-movement plans are not strongly affected by starting distance following an initial orienting fixation. Further, we replicated our prior effect of starting side (left, right) to induce a spatially contralateral tendency of fixations after the first ordinal fixation. However, we also established that these visuomotor influences did not depend upon the predictability of the location of the upcoming stimulus, and were present not only for face stimuli but also for our control stimulus category (butterflies). We found a correspondence in overall left-lateralized fixation tendency between faces and butterflies. Finally, for faces, we found a relationship between left starting side (right sided fixation pattern tendency) and increased recognition performance, which likely reflects a cortical right hemisphere (left visual hemifield) advantage for face perception. These results further indicate the importance of considering and controlling for visuomotor influences in the design, analysis, and interpretation of eye-movement studies. PMID- 26283984 TI - Late positive slow waves as markers of chunking during encoding. AB - Electrophysiological markers of chunking of words during encoding have mostly been shown in studies that present pairs of related stimuli. In these cases it is difficult to disentangle cognitive processes that reflect distinctiveness (i.e., conspicuous items because they are related), perceived association between related items and unified representations of various items, or chunking. Here, we propose a paradigm that enables the determination of a separate Event-related Potential (ERP) marker of these cognitive processes using sequentially related word triads. Twenty-three young healthy individuals viewed 80 15-word lists composed of unrelated items except for the three words in the middle serial positions (triads), which could be either unrelated (control list), related perceptually, phonetically or semantically. ERP amplitudes were measured at encoding of each one of the words in the triads. We analyzed two latency intervals (350-400 and 400-800 ms) at midline locations. Behaviorally, we observed a progressive facilitation in the immediate free recall of the words in the triads depending on the relations between their items (control < perceptual < phonetic < semantic), but only semantically related items were recalled as chunks. P300-like deflections were observed for perceptually deviant stimuli. A reduction of amplitude of a component akin to the N400 was found for words that were phonetically and semantically associated with prior items and therefore were not associated to chunking. Positive slow wave (PSW) amplitudes increased as successive phonetically and semantically related items were presented, but they were observed earlier and were more prominent at Fz for semantic associates. PSWs at Fz and Cz also correlated with recall of semantic word chunks. This confirms prior claims that PSWs at Fz are potential markers of chunking which, in the proposed paradigm, were modulated differently from the detection of deviant stimuli and of relations between stimuli. PMID- 26283983 TI - Inversion effects reveal dissociations in facial expression of emotion, gender, and object processing. AB - To distinguish between high-level visual processing mechanisms, the degree to which holistic processing is involved in facial identity, facial expression, and object perception is often examined through measuring inversion effects. However, participants may be biased by different experimental paradigms to use more or less holistic processing. Here we take a novel psychophysical approach to directly compare human face and object processing in the same experiment, with face processing broken into two categories: variant properties and invariant properties as they were tested using facial expressions of emotion and gender, respectively. Specifically, participants completed two different perceptual discrimination tasks. One involved making judgments of stimulus similarity and the other tested the ability to detect differences between stimuli. Each task was completed for both upright and inverted stimuli. Results show significant inversion effects for the detection of differences in facial expressions of emotion and gender, but not for objects. More interestingly, participants exhibited a selective inversion deficit when making similarity judgments between different facial expressions of emotion, but not for gender or objects. These results suggest a three-way dissociation between facial expression of emotion, gender, and object processing. PMID- 26283985 TI - When sexual threat cues shape attitudes toward immigrants: the role of insecurity and benevolent sexism. AB - Drawing on psychological and political science research on individuals' sensitivity to threat cues, the present study examines reactions to political posters that depict male immigrants as a sexual danger. We expect anti-immigrant attitudes to be more strongly predicted by feelings of insecurity or representations of men and women as strong and fragile when individuals are exposed to sexual threat cues than when they are not. Results from two online experiments conducted in Switzerland and Germany largely confirmed these assumptions. Comparing two anti-immigrant posters (general and non-sexual threat vs. sexual threat), Experiment 1 (n = 142) showed that feelings of insecurity were related to an increased support for expelling immigrants from the host country in both cases. However, only in the sexual threat cues condition and among female participants, were perceptions of women as fragile-as measured with benevolent sexism items-related to support for expelling immigrants. Further distinguishing between different forms of violence threat cues, Experiment 2 (n = 181) showed that collective feelings of insecurity were most strongly related to support for expelling immigrants when a male immigrant was presented as a violent criminal. In contrast, benevolent sexist beliefs were related to anti-immigrant stances only when participants were exposed to a depiction of a male immigrant as a rapist. In both cases attitudes were polarized: on the one hand, representations of immigrants as criminals provoked reactance reactions-that is, more positive attitudes-among participants scoring low in insecurity feelings or benevolent sexism. On the other hand, those scoring high in these dimensions expressed slightly more negative attitudes. Overall, by applying social psychological concepts to the study of anti-immigrant political campaigning, the present study demonstrated that individuals are sensitive to specific threat cues in posters. PMID- 26283986 TI - Social cues to joint actions: the role of shared goals. AB - In daily life, we do not just move independently from how others move. Rather, the way we move conveys information about our cognitive and affective attitudes toward our conspecifics. However, the implicit social substrate of our movements is not easy to capture and isolate given the complexity of human interactive behaviors. In this perspective article we discuss the crucial conditions for exploring the impact of "interpersonal" cognitive/emotional dimensions on the motor behavior of individuals interacting in realistic contexts. We argue that testing interactions requires one to build up naturalistic and yet controlled scenarios where participants reciprocally adapt their movements in order to achieve an overarching "shared goal." We suggest that a shared goal is what singles out real interactions from situations where two or more individuals contingently but independently act next to each other, and that "interpersonal" socio-emotional dimensions might fail to affect co-agents' behaviors if real interactions are not at place. We report the results of a novel joint-grasping task suitable for exploring how individual sub-goals (i.e., correctly grasping an object) relate to, and depend from, the representation of "shared goals." PMID- 26283988 TI - Incorporating measurement error in n = 1 psychological autoregressive modeling. AB - Measurement error is omnipresent in psychological data. However, the vast majority of applications of autoregressive time series analyses in psychology do not take measurement error into account. Disregarding measurement error when it is present in the data results in a bias of the autoregressive parameters. We discuss two models that take measurement error into account: An autoregressive model with a white noise term (AR+WN), and an autoregressive moving average (ARMA) model. In a simulation study we compare the parameter recovery performance of these models, and compare this performance for both a Bayesian and frequentist approach. We find that overall, the AR+WN model performs better. Furthermore, we find that for realistic (i.e., small) sample sizes, psychological research would benefit from a Bayesian approach in fitting these models. Finally, we illustrate the effect of disregarding measurement error in an AR(1) model by means of an empirical application on mood data in women. We find that, depending on the person, approximately 30-50% of the total variance was due to measurement error, and that disregarding this measurement error results in a substantial underestimation of the autoregressive parameters. PMID- 26283987 TI - Consciousness: individuated information in action. AB - Within theoretical and empirical enquiries, many different meanings associated with consciousness have appeared, leaving the term itself quite vague. This makes formulating an abstract and unifying version of the concept of consciousness - the main aim of this article -into an urgent theoretical imperative. It is argued that consciousness, characterized as dually accessible (cognized from the inside and the outside), hierarchically referential (semantically ordered), bodily determined (embedded in the working structures of an organism or conscious system), and useful in action (pragmatically functional), is a graded rather than an all-or-none phenomenon. A gradational approach, however, despite its explanatory advantages, can lead to some counterintuitive consequences and theoretical problems. In most such conceptions consciousness is extended globally (attached to primitive organisms or artificial systems), but also locally (connected to certain lower-level neuronal and bodily processes). For example, according to information integration theory (as introduced recently by Tononi and Koch, 2014), even such simple artificial systems as photodiodes possess miniscule amounts of consciousness. The major challenge for this article, then, is to establish reasonable, empirically justified constraints on how extended the range of a graded consciousness could be. It is argued that conscious systems are limited globally by the ability to individuate information (where individuated information is understood as evolutionarily embedded, socially altered, and private), whereas local limitations should be determined on the basis of a hypothesis about the action-oriented nature of the processes that select states of consciousness. Using these constraints, an abstract concept of consciousness is arrived at, hopefully contributing to a more unified state of play within consciousness studies itself. PMID- 26283989 TI - Sensitivity analysis in multiple imputation in effectiveness studies of psychotherapy. AB - The importance of preventing and treating incomplete data in effectiveness studies is nowadays emphasized. However, most of the publications focus on randomized clinical trials (RCT). One flexible technique for statistical inference with missing data is multiple imputation (MI). Since methods such as MI rely on the assumption of missing data being at random (MAR), a sensitivity analysis for testing the robustness against departures from this assumption is required. In this paper we present a sensitivity analysis technique based on posterior predictive checking, which takes into consideration the concept of clinical significance used in the evaluation of intra-individual changes. We demonstrate the possibilities this technique can offer with the example of irregular longitudinal data collected with the Outcome Questionnaire-45 (OQ-45) and the Helping Alliance Questionnaire (HAQ) in a sample of 260 outpatients. The sensitivity analysis can be used to (1) quantify the degree of bias introduced by missing not at random data (MNAR) in a worst reasonable case scenario, (2) compare the performance of different analysis methods for dealing with missing data, or (3) detect the influence of possible violations to the model assumptions (e.g., lack of normality). Moreover, our analysis showed that ratings from the patient's and therapist's version of the HAQ could significantly improve the predictive value of the routine outcome monitoring based on the OQ-45. Since analysis dropouts always occur, repeated measurements with the OQ-45 and the HAQ analyzed with MI are useful to improve the accuracy of outcome estimates in quality assurance assessments and non-randomized effectiveness studies in the field of outpatient psychotherapy. PMID- 26283990 TI - Metacognition-augmented cognitive remediation training reduces jumping to conclusions and overconfidence but not neurocognitive deficits in psychosis. AB - The majority of patients with schizophrenia display neurocognitive deficits (e.g., memory impairment) as well as inflated cognitive biases (e.g., jumping to conclusions). Both cognitive domains are implicated in the pathogenesis of the disorder and are known to compromise functional outcome. At present, there is a dearth of effective treatment options. A total of 90 patients with schizophrenia were recruited online (a diagnosis of schizophrenia had been confirmed in a large subgroup during a previous hospital admission). Subsequent to a baseline assessment encompassing psychopathology, self-reported cognition as well as objective memory and reasoning tests, patients were randomized to one of three conditions: standard cognitive remediation (mybraintraining), metacognition augmented cognition remediation (CR) condition (variant of mybraintraining which encouraged patients to reduce speed of decision-making and attenuate response confidence when participants made high-confidence judgements and hasty incorrect decisions) and a waitlist control group. Patients were retested after 6 weeks and again 3 months after the second assessment. Groups did not differ on psychopathology and neurocognitive parameters at any timepoint. However, at follow-up the metacognitive-augmented CR group displayed a significant reduction on jumping to conclusions and overconfidence. Treatment adherence correlated with a reduction of depression; gains in the training exercises from the standard mybraintraining condition were correlated with improved objective memory performance. The study suggests that metacognition-augmented CR may ameliorate cognitive biases but not neurocognition. The study ties in well with prior research showing that neurocognitive dysfunctions are rather resistant to change; the failure to detect significant improvement of CR or metacognition-augmented CR on psychopathology and neurocognition over time may partly be attributed to a number of methodological limitations of our study (low psychopathology and chronicity of participants, low "dosage," narrow range of tests, self-report psychopathology scales). PMID- 26283991 TI - Belief in school meritocracy as a system-justifying tool for low status students. AB - The belief that, in school, success only depends on will and hard work is widespread in Western societies despite evidence showing that several factors other than merit explain school success, including group belonging (e.g., social class, gender). In the present paper, we argue that because merit is the only track for low status students to reach upward mobility, Belief in School Meritocracy (BSM) is a particularly useful system-justifying tool to help them perceive their place in society as being deserved. Consequently, for low status students (but not high status students), this belief should be related to more general system-justifying beliefs (Study 1). Moreover, low status students should be particularly prone to endorsing this belief when their place within a system on which they strongly depend to acquire status is challenged (Study 2). In Study 1, high status (boys and high SES) were compared to low status (girls and low SES) high school students. Results indicated that BSM was related to system justifying beliefs only for low SES students and for girls, but not for high SES students or for boys. In Study 2, university students were exposed (or not) to information about an important selection process that occurs at the university, depending on the condition. Their subjective status was assessed. Although such a confrontation reduced BSM for high subjective SES students, it tended to enhance it for low subjective SES students. Results are discussed in terms of system justification motives and the palliative function meritocratic ideology may play for low status students. PMID- 26283992 TI - A longitudinal study of higher-order thinking skills: working memory and fluid reasoning in childhood enhance complex problem solving in adolescence. AB - Scientists have studied the development of the human mind for decades and have accumulated an impressive number of empirical studies that have provided ample support for the notion that early cognitive performance during infancy and childhood is an important predictor of later cognitive performance during adulthood. As children move from childhood into adolescence, their mental development increasingly involves higher-order cognitive skills that are crucial for successful planning, decision-making, and problem solving skills. However, few studies have employed higher-order thinking skills such as complex problem solving (CPS) as developmental outcomes in adolescents. To fill this gap, we tested a longitudinal developmental model in a sample of 2,021 Finnish sixth grade students (M = 12.41 years, SD = 0.52; 1,041 female, 978 male, 2 missing sex). We assessed working memory (WM) and fluid reasoning (FR) at age 12 as predictors of two CPS dimensions: knowledge acquisition and knowledge application. We further assessed students' CPS performance 3 years later as a developmental outcome (N = 1696; M = 15.22 years, SD = 0.43; 867 female, 829 male). Missing data partly occurred due to dropout and technical problems during the first days of testing and varied across indicators and time with a mean of 27.2%. Results revealed that FR was a strong predictor of both CPS dimensions, whereas WM exhibited only a small influence on one of the two CPS dimensions. These results provide strong support for the view that CPS involves FR and, to a lesser extent, WM in childhood and from there evolves into an increasingly complex structure of higher-order cognitive skills in adolescence. PMID- 26283994 TI - Approaches to assessment in time-limited Mentalization-Based Therapy for Children (MBT-C). AB - In this article we describe our clinical approach to assessment, formulation and the identification of a therapeutic focus in the context of time-limited Mentalization-Based Treatment for Children (MBT-C) aged between 6 and 12. Rather than seeing the capacity to mentalize as a global construct, we set out an approach to assessing the developmental 'building blocks' of the capacity to mentalize the self and others, including the capacity for attention regulation, emotion regulation, and explicit mentalization. Assessing the child's strengths and vulnerabilities in each of these domains provides a more nuanced picture of the child's mentalizing capacities and difficulties, and can provide a useful approach to case formulation. The article sets out an approach to assessment that includes a consideration of mentalizing strengths and difficulties in both the child and the parents, and shows how this can be used to help develop a mutually agreed treatment focus. A clinical vignette illustrates the approach taken to assessment and connects it to routine clinical practice. PMID- 26283993 TI - A macroscopic violation of no-signaling in time inequalities? How to test temporal entanglement with behavioral observables. AB - In this paper we applied for the first time the no-signaling in time (NSIT) formalism discussed by Kofler and Brukner (2013) to investigate temporal entanglement between binary human behavioral unconscious choices at t1 with binary random outcomes at t2. NSIT consists of a set of inequalities and represents mathematical conditions for macro-realism which require only two measurements in time. The analyses of three independent experiments show a strong violation of NSIT in two out of three of them, suggesting the hypothesis of a quantum-like temporal entanglement between human choices at t1 with binary random outcomes at t2. We discuss the potentialities of using NSIT to test temporal entanglement with behavioral measures. PMID- 26283995 TI - Editorial: Measurement Invariance. PMID- 26283996 TI - Emotional availability: theory, research, and intervention. AB - Attachment theory (Bowlby, 1969) and its limitations are first described. Next, emotional availability (EA; Biringen et al., 1998; Biringen, 2008) is introduced as an expansion upon the original conceptualization of the parent-child attachment relationship. As a construct and as a measure, EA considers the dyadic and emotional qualities of adult-child relationships. EA is predictive of a variety of child outcomes, such as attachment security, emotion regulation, and school readiness. Recently developed programs to enhance adult-child EA are described. PMID- 26283997 TI - Auditory verbal hallucinations in schizophrenia and post-traumatic stress disorder: common phenomenology, common cause, common interventions? AB - Auditory verbal hallucinations (AVH: 'hearing voices') are found in both schizophrenia and post-traumatic stress disorder (PTSD). In this paper we first demonstrate that AVH in these two diagnoses share a qualitatively similar phenomenology. We then show that the presence of AVH in schizophrenia is often associated with earlier exposure to traumatic/emotionally overwhelming events, as it is by definition in PTSD. We next argue that the content of AVH relates to earlier traumatic events in a similar way in both PTSD and schizophrenia, most commonly having direct or indirect thematic links to emotionally overwhelming events, rather than being direct re-experiencing. We then propose, following cognitive models of PTSD, that the reconstructive nature of memory may be able to account for the nature of these associations between trauma and AVH content, as may threat-hypervigilance and the individual's personal goals. We conclude that a notable subset of people diagnosed with schizophrenia with AVH are having phenomenologically and aetiologically identical experiences to PTSD patients who hear voices. As such we propose that the iron curtain between AVH in PTSD (often termed 'dissociative AVH') and AVH in schizophrenia (so-called 'psychotic AVH') needs to be torn down, as these are often the same experience. One implication of this is that these trauma-related AVH require a common trans-diagnostic treatment strategy. Whilst antipsychotics are already increasingly being used to treat AVH in PTSD, we argue for the centrality of trauma-based interventions for trauma based AVH in both PTSD and in people diagnosed with schizophrenia. PMID- 26283998 TI - Will understanding vision require a wholly empirical paradigm? AB - Based on electrophysiological and anatomical studies, a prevalent conception is that the visual system recovers features of the world from retinal images to generate perceptions and guide behavior. This paradigm, however, is unable to explain why visual perceptions differ from physical measurements, or how behavior could routinely succeed on this basis. An alternative is that vision does not recover features of the world, but assigns perceptual qualities empirically by associating frequently occurring stimulus patterns with useful responses on the basis of survival and reproductive success. The purpose of the present article is to briefly describe this strategy of vision and the evidence for it. PMID- 26283999 TI - Executive functions in mono- and bilingual children with language impairment - issues for speech-language pathology. AB - The clinical assessment of language impairment (LI) in bilingual children imposes challenges for speech-language pathology services. Assessment tools standardized for monolingual populations increase the risk of misinterpreting bilingualism as LI. This Perspective article summarizes recent studies on the assessment of bilingual LI and presents new results on including non-linguistic measures of executive functions in the diagnostic assessment. Executive functions shows clinical utility as less subjected to language use and exposure than linguistic measures. A possible bilingual advantage, and consequences for speech-language pathology practices and future research are discussed. PMID- 26284000 TI - One size does not fit all: older adults benefit from redundant text in multimedia instruction. AB - The multimedia design of presentations typically ignores that younger and older adults have varying cognitive strengths and weaknesses. We examined whether differential instructional design may enhance learning in these populations. Younger and older participants viewed one of three computer-based presentations: Audio only (narration), Redundant (audio narration with redundant text), or Complementary (audio narration with non-redundant text and images). Younger participants learned better when audio narration was paired with relevant images compared to when audio narration was paired with redundant text. However, older participants learned best when audio narration was paired with redundant text. Younger adults, who presumably have a higher working memory capacity (WMC), appear to benefit more from complementary information that may drive deeper conceptual processing. In contrast, older adults learn better from presentations that support redundant coding across modalities, which may help mitigate the effects of age-related decline in WMC. Additionally, several misconceptions of design quality appeared across age groups: both younger and older participants positively rated less effective designs. Findings suggest that one-size does not fit all, with older adults requiring unique multimedia design tailored to their cognitive abilities for effective learning. PMID- 26284001 TI - Deriving meaning from others' emotions: attribution, appraisal, and the use of emotions as social information. AB - Emotional expressions constitute a rich source of information. Integrating theorizing on attribution, appraisal processes, and the use of emotions as social information, we examined how emotional expressions influence attributions of agency and responsibility under conditions of ambiguity. Three vignette studies involving different scenarios indicate that participants used information about others' emotional expressions to make sense of ambiguous social situations. Expressions of regret fueled inferences that the expresser was responsible for an adverse situation, whereas expressions of anger fueled inferences that someone else was responsible. Also, expressions of anger were interpreted as a sign of injustice, and expressions of disappointment increased prosocial intentions (i.e., to help the expresser). The results show that emotional expressions can help people understand ambiguous social situations by informing attributions that correspond with each emotion's associated appraisal structures. The findings advance understanding of the ways in which emotional expressions help individuals understand and coordinate social life. PMID- 26284002 TI - Parental bereavement and the loss of purpose in life as a function of interdependent self-construal. AB - Children are often inextricably linked to their parents' hopes and dreams. As such, the loss of a child often represents one of the most traumatic experiences possible. The current research explores how this specific loss relates to one's sense of purpose in life. We further explore whether the loss of a child is particularly detrimental to one's sense of purpose for highly interdependent parents. Analyses of parents from the Midlife in the United States data set revealed, as expected, that the loss of child negatively predicts one's sense of purpose in life, and that this effect is most pronounced for parents high in interdependent self-construal. Potential mechanisms and implications of the present findings are discussed. PMID- 26284003 TI - Editorial: Character, responsibility, and well-being: influences on mental health and constructive behavior patterns. PMID- 26284004 TI - Rewards modulate saccade latency but not exogenous spatial attention. AB - The eye movement system is sensitive to reward. However, whilst the eye movement system is extremely flexible, the extent to which changes to oculomotor behavior induced by reward paradigms persist beyond the training period or transfer to other oculomotor tasks is unclear. To address these issues we examined the effects of presenting feedback that represented small monetary rewards to spatial locations on the latency of saccadic eye movements, the time-course of learning and extinction of the effects of rewarding saccades on exogenous spatial attention and oculomotor inhibition of return. Reward feedback produced a relative facilitation of saccadic latency in a stimulus driven saccade task which persisted for three blocks of extinction trials. However, this hemifield-specific effect failed to transfer to peripheral cueing tasks. We conclude that rewarding specific spatial locations is unlikely to induce long-term, systemic changes to the human oculomotor or attention systems. PMID- 26284005 TI - Cognitive training for children with ADHD: a randomized controlled trial of cogmed working memory training and 'paying attention in class'. AB - The goal of this randomized controlled trial was to replicate and extend previous studies of Cogmed Working Memory Training (CWMT) in children with Attention deficit/hyperactivity disorder (ADHD). While a large proportion of children with ADHD suffer from academic difficulties, only few previous efficacy studies have taken into account long term academic outcome measures. So far, results regarding academic outcome measures have been inconsistent. Hundred and two children with ADHD between the age of 8 and 12 years (both medicated and medication naive) participated in current randomized controlled trial. Children were randomly assigned to CWMT or a new active combined working memory- and executive function compensatory training called 'Paying Attention in Class.' Primary outcome measures were neurocognitive functioning and academic performance. Secondary outcome measures contained ratings of behavior in class, behavior problems, and quality of life. Assessment took place before, directly after and 6 months after treatment. Results showed only one replicated treatment effect on visual spatial working memory in favor of CWMT. Effects of time were found for broad neurocognitive measures, supported by parent and teacher ratings. However, no treatment or time effects were found for the measures of academic performance, behavior in class or quality of life. We suggest that methodological and non specific treatment factors should be taken into account when interpreting current findings. Future trials with well-blinded measures and a third 'no treatment' control group are needed before cognitive training can be supported as an evidence-based treatment of ADHD. Future research should put more effort into investigating why, how and for whom cognitive training is effective as this would also potentially lead to improved intervention- and study designs. PMID- 26284007 TI - Examination of the suitability of collecting in event cognitive processes using Think Aloud protocol in golf. AB - Two studies examined the use of Think Aloud (TA) protocol as a means for collecting data of cognitive processes during performance in golf. In Study 1, TA was employed to examine if different verbalisation (Level 2 or Level 3 TA) instructions influence performance of high and low skilled golfers. Participants performed 30 putts using TA at either Levels 2, 3, or no verbalization condition. Although Level 3 verbalization produced a higher volume of verbal data than Level 2, TA at either Level 2 or 3 did not impair putting performance compared to no verbalization. Study 2 examined the congruence between data collected via TA at Level 3 and cued retrospective recall of cognitive processes during golf performance. Experienced golfers performed six holes of golf whilst engaging in Level 3 TA. After performance, three semi-structured retrospective interviews were conducted (10 min after performance, 24 h after performance and 48 h after performance). A comparison of the themes identified large discrepancies between the information reported during TA and at interview, with only 38-41% similarity in variables reported to influence decision making on each hole. Both studies suggest TA is a valuable method for recording cognitive processes of individuals during task performance. TA provides richer verbal data regarding decisions than cued retrospective recall, and TA does not negatively impact performance. PMID- 26284006 TI - Can a bird brain do phonology? AB - A number of recent studies have revealed correspondences between song- and language-related neural structures, pathways, and gene expression in humans and songbirds. Analyses of vocal learning, song structure, and the distribution of song elements have similarly revealed a remarkable number of shared characteristics with human speech. This article reviews recent developments in the understanding of these issues with reference to the phonological phenomena observed in human language. This investigation suggests that birds possess a host of abilities necessary for human phonological computation, as evidenced by behavioral, neuroanatomical, and molecular genetic studies. Vocal-learning birds therefore present an excellent model for studying some areas of human phonology, though differences in the primitives of song and language as well as the absence of a human-like morphosyntax make human phonology differ from birdsong phonology in crucial ways. PMID- 26284009 TI - Investigating the role of self-construal in the formation of entrepreneurial intentions. AB - Individuals may perceive themselves as independent and distinct from others or as interdependent and connected to others. Do these differences in self-construal influence entrepreneurial preferences and intentions to start a new business in university students? Few studies have examined the influence of cultural orientations on entrepreneurial intentions at the individual level of analysis. Two studies investigated the role of independent and interdependent self construal within the theory of planned behavior (TPB). In the first study, results from structural equation modeling analyses found that chronic independent self-construal was related to attitudes toward entrepreneurship and moderated relationships between attitudes and entrepreneurial intentions. In the second study, participants primed with an independent self-construal had more favorable entrepreneurial attitudes, but not intentions than participants primed with an interdependent focus. This set of studies extends cognitive models of entrepreneurship by demonstrating the role of self-construal in the TPB model at individual level. PMID- 26284008 TI - Audition and vision share spatial attentional resources, yet attentional load does not disrupt audiovisual integration. AB - Humans continuously receive and integrate information from several sensory modalities. However, attentional resources limit the amount of information that can be processed. It is not yet clear how attentional resources and multisensory processing are interrelated. Specifically, the following questions arise: (1) Are there distinct spatial attentional resources for each sensory modality? and (2) Does attentional load affect multisensory integration? We investigated these questions using a dual task paradigm: participants performed two spatial tasks (a multiple object tracking task and a localization task), either separately (single task condition) or simultaneously (dual task condition). In the multiple object tracking task, participants visually tracked a small subset of several randomly moving objects. In the localization task, participants received either visual, auditory, or redundant visual and auditory location cues. In the dual task condition, we found a substantial decrease in participants' performance relative to the results of the single task condition. Importantly, participants performed equally well in the dual task condition regardless of the location cues' modality. This result suggests that having spatial information coming from different modalities does not facilitate performance, thereby indicating shared spatial attentional resources for the auditory and visual modality. Furthermore, we found that participants integrated redundant multisensory information similarly even when they experienced additional attentional load in the dual task condition. Overall, findings suggest that (1) visual and auditory spatial attentional resources are shared and that (2) audiovisual integration of spatial information occurs in an pre-attentive processing stage. PMID- 26284010 TI - Audiovisual crossmodal cuing effects in front and rear space. AB - The participants in the present study had to make speeded elevation discrimination responses to visual targets presented to the left or right of central fixation following the presentation of a task-irrelevant auditory cue on either the same or opposite side. In Experiment 1, the cues were presented from in front of the participants (from the same azimuthal positions as the visual targets). A standard crossmodal exogenous spatial cuing effect was observed, with participants responding significantly faster in the elevation discrimination task to visual targets when both the auditory cues and the visual targets were presented on the same side. Experiment 2 replicated the exogenous spatial cuing effect for frontal visual targets following both front and rear auditory cues. The results of Experiment 3 demonstrated that the participants had little difficulty in correctly discriminating the location from which the sounds were presented. Thus, taken together, the results of the three experiments reported here demonstrate that the exact co-location of auditory cues and visual targets is not necessary to attract spatial attention. Implications of these results for the design of real-world warning signals are discussed. PMID- 26284011 TI - Determinants of judgment and decision making quality: the interplay between information processing style and situational factors. AB - A framework is presented to better characterize the role of individual differences in information processing style and their interplay with contextual factors in determining decision making quality. In Experiment 1, we show that individual differences in information processing style are flexible and can be modified by situational factors. Specifically, a situational manipulation that induced an analytical mode of thought improved decision quality. In Experiment 2, we show that this improvement in decision quality is highly contingent on the compatibility between the dominant thinking mode and the nature of the task. That is, encouraging an intuitive mode of thought led to better performance on an intuitive task but hampered performance on an analytical task. The reverse pattern was obtained when an analytical mode of thought was encouraged. We discuss the implications of these results for the assessment of decision making competence, and suggest practical directions to help individuals better adjust their information processing style to the situation at hand and make optimal decisions. PMID- 26284012 TI - Deceit and facial expression in children: the enabling role of the "poker face" child and the dependent personality of the detector. AB - This study presents the relation between the facial expression of a group of children when they told a lie and the accuracy in detecting the lie by a sample of adults. To evaluate the intensity and type of emotional content of the children's faces, we applied an automated method capable of analyzing the facial information from the video recordings (FaceReader 5.0 software). The program classified videos as showing a neutral facial expression or an emotional one. There was a significant higher mean of hits for the emotional than for the neutral videos, and a significant negative correlation between the intensity of the neutral expression and the number of hits from the detectors. The lies expressed with emotional facial expression were more easily recognized by adults than the lies expressed with a "poker face"; thus, the less expressive the child the harder it was to guess. The accuracy of the lie detectors was then correlated with their subclinical traits of personality disorders, to find that participants scoring higher in the dependent personality were significantly better lie detectors. A non-significant tendency for women to discriminate better was also found, whereas men tended to be more suspicious than women when judging the children's veracity. This study is the first to automatically decode the facial information of the lying child and relate these results with personality characteristics of the lie detectors in the context of deceptive behavior research. Implications for forensic psychology were suggested: to explore whether the induction of an emotion in a child during an interview could be useful to evaluate the testimony during legal trials. PMID- 26284013 TI - The relation between receptive grammar and procedural, declarative, and working memory in specific language impairment. AB - What memory systems underlie grammar in children, and do these differ between typically developing (TD) children and children with specific language impairment (SLI)? Whilst there is substantial evidence linking certain memory deficits to the language problems in children with SLI, few studies have investigated multiple memory systems simultaneously, examining not only possible memory deficits but also memory abilities that may play a compensatory role. This study examined the extent to which procedural, declarative, and working memory abilities predict receptive grammar in 45 primary school aged children with SLI (30 males, 15 females) and 46 TD children (30 males, 16 females), both on average 9;10 years of age. Regression analyses probed measures of all three memory systems simultaneously as potential predictors of receptive grammar. The model was significant, explaining 51.6% of the variance. There was a significant main effect of learning in procedural memory and a significant group * procedural learning interaction. Further investigation of the interaction revealed that procedural learning predicted grammar in TD but not in children with SLI. Indeed, procedural learning was the only predictor of grammar in TD. In contrast, only learning in declarative memory significantly predicted grammar in SLI. Thus, different memory systems are associated with receptive grammar abilities in children with SLI and their TD peers. This study is, to our knowledge, the first to demonstrate a significant group by memory system interaction in predicting grammar in children with SLI and their TD peers. In line with Ullman's Declarative/Procedural model of language and procedural deficit hypothesis of SLI, variability in understanding sentences of varying grammatical complexity appears to be associated with variability in procedural memory abilities in TD children, but with declarative memory, as an apparent compensatory mechanism, in children with SLI. PMID- 26284014 TI - Treating verbal working memory in a boy with intellectual disability. AB - The present case study investigates the effects of a cognitive training of verbal working memory that was proposed for Davide, a 14-year-old boy diagnosed with mild intellectual disability. The program stimulated attention, inhibition, switching, and the ability to engage either in verbal dual tasks or in producing inferences after the content of a short passage had been encoded in episodic memory. Key elements in our program included (1) core training of target cognitive mechanisms; (2) guided practice emphasizing concrete strategies to engage in exercises; and (3) a variable amount of adult support. The study explored whether such a complex program produced "near transfer" effects on an untrained dual task assessing verbal working memory and whether effects on this and other target cognitive mechanisms (i.e., attention, inhibition, and switching) were long-lasting and produced "far transfer" effects on cognitive flexibility. The effects of the intervention program were investigated with a research design consisting of four subsequent phases lasting 8 or 10 weeks, each preceded and followed by testing. There was a control condition (phase 1) in which the boy received, at home, a stimulation focused on the visuospatial domain. Subsequently, there were three experimental training phases, in which stimulation in the verbal domain was first focused on attention and inhibition (phase 2a), then on switching and simple working memory tasks (phase 2b), then on complex working memory tasks (phase 3). A battery of neuropsychological tests was administered before and after each training phase and 7 months after the conclusion of the intervention. The main finding was that Davide changed from being incapable of addressing the dual task request of the listening span test in the initial assessment to performing close to the normal limits of a 13-year-old boy in the follow-up assessment with this test, when he was 15 years old. PMID- 26284015 TI - Temporal attending and prediction influence the perception of metrical rhythm: evidence from reaction times and ERPs. AB - The processing of rhythmic events in music is influenced by the induced metrical structure. Two mechanisms underlying this may be temporal attending and temporal prediction. Temporal fluctuations in attentional resources may influence the processing of rhythmic events by heightening sensitivity at metrically strong positions. Temporal predictions may attenuate responses to events that are highly expected within a metrical structure. In the current study we aimed to disentangle these two mechanisms by examining responses to unexpected sounds, using intensity increments and decrements as deviants. Temporal attending was hypothesized to lead to better detection of deviants in metrically strong (on the beat) than weak (offbeat) positions due to heightened sensitivity on the beat. Temporal prediction was hypothesized to lead to best detection of increments in offbeat positions and decrements on the beat, as they would be most unexpected in these positions. We used a speeded detection task to measure detectability of the deviants under attended conditions (Experiment 1). Under unattended conditions (Experiment 2), we used EEG to measure the mismatch negativity (MMN), an ERP component known to index the detectability of unexpected auditory events. Furthermore, we examined the amplitude of the auditory evoked P1 and N1 responses, which are known to be sensitive to both attention and prediction. We found better detection of small increments in offbeat positions than on the beat, consistent with the influence of temporal prediction (Experiment 1). In addition, we found faster detection of large increments on the beat as opposed to offbeat (Experiment 1), and larger amplitude P1 responses on the beat as compared to offbeat, both in support of temporal attending (Experiment 2). As such, we showed that both temporal attending and temporal prediction shape our processing of metrical rhythm. PMID- 26284016 TI - Engagement in dance is associated with emotional competence in interplay with others. AB - This study has explored the relation between dance achievement and alexithymia in a larger Swedish population sample (Swedish Twin Registry) with a study sample of 5431 individuals. Dance achievement (CAQ) was assessed in relation to Alexithymia (Toronto Alexithymia Scale, TAS-20) including the three subscales: Difficulty Identifying Feelings (DIF), Difficulty Describing Feelings (DDF), and Externally Oriented Thinking (EOT). The results show a significant negative association between the TAS subscale (EOT) and creative achievement in dance. A high EOT score corresponds to poor ability to communicate feelings to the environment. There was no consistent association between the other factors DIF and DDF and dance achievement. Dance activity and training seem to be involved in the body's emotional interplay with others. Embodied cognition, emotional perception, and action are discussed as factors relevant to measuring the skill of a dancer. PMID- 26284017 TI - Working memory training: from metaphors to models. PMID- 26284018 TI - Four broad temperament dimensions: description, convergent validation correlations, and comparison with the Big Five. AB - A new temperament construct based on recent brain physiology literature has been investigated using the Fisher Temperament Inventory (FTI). Four collections of behaviors emerged, each associated with a specific neural system: the dopamine, serotonin, testosterone, and estrogen/oxytocin system. These four temperament suites have been designated: (1) Curious/Energetic, (2) Cautious/Social Norm Compliant, (3) Analytical/Tough-minded, and (4) Prosocial/Empathetic temperament dimensions. Two functional magnetic resonance imaging (fMRI) studies have suggested that the FTI can measure the influence of these neural systems. In this paper, to further the behavioral validation and characterization of the four proposed temperament dimensions, we measured correlations with five variables: (1) gender; (2) level of education; (3) religious preference; (4) political orientation; (5) the degree to which an individual regards sex as essential to a successful relationship. Subjects were 39,913 anonymous members of a US Internet dating site and 70,000+ members in six other countries. Correlations with the five variables characterize the FTI and are consistent with mechanisms using the proposed neuromodulators. We also report on an analysis between the FTI and the NEO-Five Factor Inventory, using a college sample (n = 215), which showed convergent validity. The results provide novel correlates not available in other questionnaires: religiosity, political orientation, and attitudes about sex in a relationship. Also, an Eigen analysis replicated the four clusters of co-varying items. The FTI, with its broad systems and non-pathologic factors complements existing personality questionnaires. It provides an index of some brain systems that contribute to temperament, and may be useful in psychotherapy, business, medicine, and the legal community. PMID- 26284021 TI - Change blindness in pigeons (Columba livia): the effects of change salience and timing. AB - Change blindness is a well-established phenomenon in humans, in which plainly visible changes in the environment go unnoticed. Recently a parallel change blindness phenomenon has been demonstrated in pigeons. The reported experiment follows up on this finding by investigating whether change salience affects change blindness in pigeons the same way it affects change blindness in humans. Birds viewed alternating displays of randomly generated lines back-projected onto three response keys, with one or more line features on a single key differing between consecutive displays. Change salience was manipulated by varying the number of line features that changed on the critical response key. Results indicated that change blindness is reduced if a change is made more salient, and this matches previous human results. Furthermore, accuracy patterns indicate that pigeons' effective search area expanded over the course of a trial to encompass a larger portion of the stimulus environment. Thus, the data indicate two important aspects of temporal cognition. First, the timing of a change has a profound influence on whether or not that change will be perceived. Second, pigeons appear to engage in a serial search for changes, in which additional time is required to search additional locations. PMID- 26284019 TI - Fifty psychological and psychiatric terms to avoid: a list of inaccurate, misleading, misused, ambiguous, and logically confused words and phrases. AB - The goal of this article is to promote clear thinking and clear writing among students and teachers of psychological science by curbing terminological misinformation and confusion. To this end, we present a provisional list of 50 commonly used terms in psychology, psychiatry, and allied fields that should be avoided, or at most used sparingly and with explicit caveats. We provide corrective information for students, instructors, and researchers regarding these terms, which we organize for expository purposes into five categories: inaccurate or misleading terms, frequently misused terms, ambiguous terms, oxymorons, and pleonasms. For each term, we (a) explain why it is problematic, (b) delineate one or more examples of its misuse, and (c) when pertinent, offer recommendations for preferable terms. By being more judicious in their use of terminology, psychologists and psychiatrists can foster clearer thinking in their students and the field at large regarding mental phenomena. PMID- 26284020 TI - Promoting the use of personally relevant stimuli for investigating patients with disorders of consciousness. AB - Sensory stimuli are used to evaluate and to restore cognitive functions and consciousness in patients with a disorder of consciousness (DOC) following a severe brain injury. Although sophisticated protocols can help assessing higher order cognitive functions and awareness, one major drawback is their lack of sensitivity. The aim of the present review is to show that stimulus selection is crucial for an accurate evaluation of the state of patients with disorders of consciousness as it determines the levels of processing that the patient can have with stimulation from his/her environment. The probability to observe a behavioral response or a cerebral response is increased when her/his personal history and/or her/his personal preferences are taken into account. We show that personally relevant stimuli (i.e., with emotional, autobiographical, or self related characteristics) are associated with clearer signs of perception than are irrelevant stimuli in patients with DOC. Among personally relevant stimuli, music appears to be a promising clinical tool as it boosts perception and cognition in patients with DOC and could also serve as a prognostic tool. We suggest that the effect of music on cerebral processes in patients might reflect the music's capacity to act both on the external and internal neural networks supporting consciousness. PMID- 26284022 TI - Children's mental representations with respect to caregivers and post-traumatic symptomatology in Somatic Symptom Disorders and Disruptive Behavior Disorders. AB - INTRODUCTION: In line with literature, the quality of adult-infant interactions and mental representations of the caregivers play an essential role in influencing the children's well-being. Many studies focused the attention on the role of attachment for a better evaluation of child psychopathological outcomes. The flexibility of the child's attachment model gives the opportunity to parents to be helped in modifying their own caregiving quality, encouraging the reflection on the children's state of mind with respect to attachment. The aims of this study were to evaluate: (1) the attachment models in young patients diagnosed with Disruptive Behavior Disorders (DBDs) and Somatic Symptoms Disorders (SSDs); (2) the levels of post-traumatic symptomatology; (3) the association between the attachment models and post-traumatic symptomatology. METHODS: Forty Italian patients, aged from 8 to 15, recruited at Gaslini Paediatric Hospital of Genoa, previously diagnosed with SSD (N = 20) and DBD (N = 20) were assessed using the Child Attachment Interview (CAI), the Separation Anxiety Test (SAT), the Trauma Symptom Checklist for Children (TSCC-A). Socio demographic data were collected. RESULTS: In both the clinical samples, the findings on the distribution of attachment models showed a significant presence of insecure attachment with respect to both parents in more than a half of the patients and high levels of disorganized attachment. No significant differences between DBD and SSD samples were found on post-traumatic symptomatology (Post Traumatic Stress and Dissociation). Significant differences were found on Depression, Anxiety, and Fantasy subscales. DISCUSSION: This study can provide a detection of dysfunctional aspects in clinical populations. The findings suggest that the quality of the attachment to parents may be a fundamental element to better assess SSD and DBD in children and adolescents. Clinical implications of this study aimed at improving parental caregiving are highlighted. PMID- 26284023 TI - Maintaining Balance when Looking at a Virtual Reality Three-Dimensional Display of a Field of Moving Dots or at a Virtual Reality Scene. AB - EXPERIMENTAL OBJECTIVE: To provide a safe, simple, relatively inexpensive, fast, accurate way of quantifying balance performance either in isolation, or in the face of challenges provided by 3D high definition moving visual stimuli as well as by the proprioceptive challenge from standing on a foam pad. This method uses the new technology of the Wii balance board to measure postural stability during powerful, realistic visual challenges from immersive virtual reality. LIMITATIONS OF CURRENT TECHNIQUES: Present computerized methods for measuring postural stability are large, complex, slow, and expensive, and do not allow for testing the response to realistic visual challenges. PROTOCOL: Subjects stand on a 6 cm thick, firm, foam pad on a Wii balance board. They wear a fast, high resolution, low persistence, virtual reality head set (Oculus Rift DK2). This allows displays of varying speed, direction, depth, and complexity to be delivered. The subject experiences a visual illusion of real objects fixed relative to the world, and any of these displays can be perturbed in an unpredictable fashion. A special app (BalanceRite) used the same procedures for analyzing postural analysis as used by the Equitest. POWER OF THE TECHNIQUE: Four simple "proof of concept" experiments demonstrate that this technique matches the gold standard Equitest in terms of the measurement of postural stability but goes beyond the Equitest by measuring stability in the face of visual challenges, which are so powerful that even healthy subjects fall. The response to these challenges presents an opportunity for predicting falls and for rehabilitation of seniors and patients with poor postural stability. SIGNIFICANCE FOR THE FIELD: This new method provides a simpler, quicker, cheaper method of measurement than the Equitest. It may provide a new mode of training to prevent falls, by maintaining postural stability in the face of visual and proprioceptive challenges similar to those encountered in life. PMID- 26284024 TI - Improvement in Touch Sensation after Stroke is Associated with Resting Functional Connectivity Changes. AB - BACKGROUND: Distributed brain networks are known to be involved in facilitating behavioral improvement after stroke, yet few, if any, studies have investigated the relationship between improved touch sensation after stroke and changes in functional brain connectivity. OBJECTIVE: We aimed to identify how recovery of somatosensory function in the first 6 months after stroke was associated with functional network changes as measured using resting-state connectivity analysis of functional magnetic resonance imaging (fMRI) data. METHODS: Ten stroke survivors underwent clinical testing and resting-state fMRI scans at 1 and 6 months post-stroke. Ten age-matched healthy participants were included as controls. RESULTS: Patients demonstrated a wide range of severity of touch impairment 1 month post-stroke, followed by variable improvement over time. In the stroke group, significantly stronger interhemispheric functional correlations between regions of the somatosensory system, and with visual and frontal areas, were found at 6 months than at 1 month post-stroke. Clinical improvement in touch discrimination was associated with stronger correlations at 6 months between contralesional secondary somatosensory cortex (SII) and inferior parietal cortex and middle temporal gyrus, and between contralesional thalamus and cerebellum. CONCLUSION: The strength of connectivity between somatosensory regions and distributed brain networks, including vision and attention networks, may change over time in stroke survivors with impaired touch discrimination. Connectivity changes from contralesional SII and contralesional thalamus are associated with improved touch sensation at 6 months post-stroke. These functional connectivity changes could represent future targets for therapy. PMID- 26284025 TI - Treating a GAD65 Antibody-Associated Limbic Encephalitis with Basiliximab: A Case Study. AB - BACKGROUND: Antibodies (ABs) against the 65-kDa isoform of the intracellular enzyme glutamate decarboxylase (GAD65) have been found in limbic encephalitis (LE) and other neurological conditions. The direct significance of anti-GAD65-ABs for epilepsy is unclear. However, in histological preparations from biopsies of resective epilepsy surgeries, predominantly cytotoxic T-lymphocytes were detected making close contacts to neurons. Activated T-lymphocytes can, in turn, be selectively controlled by therapeutic interleukin-2 receptor Abs, such as basiliximab. CASE PRESENTATION: We report of a 25-year-old male patient with epilepsy since the age of 18 and displaying clinical signs of LE and a high titer of GAD65 ABs in cerebrospinal fluid (CSF) and serum. Monthly, repetitive, intravenous cortisone pulse therapies that were initially administered for 6 months failed to improve his condition. Subsequent flow-cytometry analysis of CSF showed especially an increased fraction of activated HLA-DR(+) CD8(+) T lymphocytes (fCD8(+)TL) when compared to controls. Thus, a second, intravenous cortisone pulse therapy with an additional basiliximab dose of 20 mg/month was started. After 3 months, the fCD8(+)TL in the CSF normalized; after 6 months, the psychological impulse-control deficits normalized; and after 11 months the patient was seizure free. However, 7 weeks later, seizures and, later on, psychological deficits recurred and fCD8(+)TL was once again present in the CSF. Flumazenil PET, magnetic resonance imaging-volumetry, and neuropsychological changes during therapy are described. CONCLUSION: The correlation of the fCD8(+)TL in the CSF with clinical and paraclinical measures of disease activity combined with the unambiguous response to basiliximab strongly argues in favor of the putative pathogenic role fCD8(+)TL in anti-GAD65 LE. The clinical relapse at the end of the observation period might be due to the formation of human anti drug ABs, a well-known complication of therapy with chimeric ABs. PMID- 26284027 TI - Hepatic CEACAM1 Over-Expression Protects Against Diet-Induced Fibrosis and Inflammation in White Adipose Tissue. AB - CEACAM1 promotes insulin extraction, an event that occurs mainly in liver. Phenocopying global Ceacam1 null mice (Cc1(-/-) ), C57/BL6J mice fed a high-fat (HF) diet exhibited reduced hepatic CEACAM1 levels and impaired insulin clearance, followed by hyperinsulinemia, insulin resistance, and visceral obesity. Conversely, forced liver-specific expression of CEACAM1 protected insulin sensitivity and energy expenditure, and limited gain in total fat mass by HF diet in L-CC1 mice. Because CEACAM1 protein is barely detectable in white adipose tissue (WAT), we herein investigated whether hepatic CEACAM1-dependent insulin clearance pathways regulate adipose tissue biology in response to dietary fat. While HF diet caused a similar body weight gain in L-CC1, this effect was delayed and less intense relative to wild-type (WT) mice. Histological examination revealed less expansion of adipocytes in L-CC1 than WT by HF intake. Immunofluorescence analysis demonstrated a more limited recruitment of crown-like structures, and qRT-PCR analysis showed no significant rise in TNFalpha mRNA levels in response to HF intake in L-CC1 than WT mice. Unlike WT, HF diet did not activate TGF-beta in WAT of L-CC1 mice, as assessed by Western analysis of Smad2/3 phosphorylation. Consistently, HF diet caused relatively less collagen deposition in L-CC1 than WT mice, as shown by Trichrome staining. Coupled with reduced lipid redistribution from liver to visceral fat, lower inflammation and fibrosis could contribute to protected energy expenditure against HF diet in L CC1 mice. The data underscore the important role of hepatic insulin clearance in the regulation of adipose tissue inflammation and fibrosis. PMID- 26284028 TI - Familial Non-Medullary Thyroid Cancer Represents an Independent Risk Factor for Increased Cancer Aggressiveness: A Retrospective Analysis of 74 Families. AB - OBJECTIVES: To assess whether familial non-medullary thyroid cancer (FNMTC) represents an independent risk factor for increased aggressiveness of the tumor, as concern as the clinical presentation and the long-term follow-up in respect of sporadic differentiated thyroid cancer (SDTC). DESIGN: Retrospective study; 1976 2014. PATIENTS AND METHODS: Seventy-four FNMTC families (151 affected individuals): family relationship and number of affected family members were evaluated. Clinical and histopathological features and outcome were compared to that of 643 SDTC patients followed in the same period according to the same institutional protocols. Median follow-up was 57.7 months (range 12-136) in FNMTC and 59.7 (range 15-94.6) in SDTC patients. RESULTS: Three cases occurred in 3 families and 2 cases in the other 71. F:M was 3.7:1 in FNMTC and 4.3:1 in SDTC (NS). The family relationship was siblings in 62.2%. Mean age at diagnosis was lower in FNMTC than in SDTC (p < 0.005). Papillary/follicular histotype distribution was similar (86%). Papillary tumors were more frequently multifocal in FNMTC (p = 0.004) and with lymph-node metastases (p = 0.016). Disease-free survival (DFS) was shorter in FNMTC vs. SDTC (p < 0.0001) with 74.8 vs. 90.8% patients free of disease at the last control (p < 0.005). Three patients died in FNMTC group vs. 1 in SDTC (p = 0.02). CONCLUSION: Familial non-medullary thyroid cancer displays distinct characteristics as earlier age of onset and increased aggressiveness at diagnosis and a higher rate of persistent/recurrent disease and mortality with a shorter DFS in respect with SDTC. FNMTC patients, therefore, should be followed accurately. As the specific gene (or genes) responsible for susceptibility for FNMTC has not yet been identified, a low frequency periodic screening of relatives DTC patients may be useful to identify FNMTC patients at early stage of disease. PMID- 26284029 TI - Venus Kinase Receptors at the Crossroads of Insulin Signaling: Their Role in Reproduction for Helminths and Insects. AB - Venus kinase receptors (VKRs) are invertebrate receptor tyrosine kinases (TKs) first discovered in the human parasite Schistosoma. They contain an extracellular Venus FlyTrap module similar to the ligand-binding domain of G protein-coupled receptors of class C and an intracellular TK domain similar to that of insulin receptors. VKRs are present from cnidarians to echinoderms. They were shown to be activated by amino-acids, to induce insulin-like intracellular pathways, and to be highly expressed in larvae and in gonads of helminths and insects. The function of VKR in gametogenesis was demonstrated in schistosomes by VKR silencing and recent studies in Aedes aegypti have confirmed the importance of VKR in mosquito egg formation. AaeVKR was shown to bind to ovary ecdysteroidogenic hormone and to activate the production of ecdysteroids by the ovary, independently of signaling mediated by insulin-like peptides. These new data confirm and specify the function of VKRs in the reproduction of helminths and insects and they open interesting perspectives for elucidating the role of VKRs in other models. VKR targeting would also provide opportunities for the control of parasites and various vector-borne infectious diseases. PMID- 26284026 TI - Limbic Encephalitis: Potential Impact of Adaptive Autoimmune Inflammation on Neuronal Circuits of the Amygdala. AB - Limbic encephalitis is characterized by adaptive autoimmune inflammation of the gray matter structures of the limbic system. It has recently been identified as a major cause of temporal lobe epilepsy accompanied by progressive declarative - mainly episodic - -memory disturbance as well as a variety of rather poorly defined emotional and behavioral changes. While autoimmune inflammation of the hippocampus is likely to be responsible for declarative memory disturbance, consequences of autoimmune inflammation of the amygdala are largely unknown. The amygdala is central for the generation of adequate homoeostatic behavioral responses to emotionally significant external stimuli following processing in a variety of parallel neuronal circuits. Here, we hypothesize that adaptive cellular and humoral autoimmunity may target and modulate distinct inhibitory or excitatory neuronal networks within the amygdala, and thereby strongly impact processing of emotional stimuli and corresponding behavioral responses. This may explain some of the rather poorly understood neuropsychiatric symptoms in limbic encephalitis. PMID- 26284030 TI - Contribution of Acinetobacter-derived cephalosporinase-30 to sulbactam resistance in Acinetobacter baumannii. AB - The sulbactam resistance rate in Acinetobacter baumannii has increased worldwide. Previous reports have shown that the beta-lactamase bla TEM-1 confers resistance to sulbactam in A. baumannii. The purpose of this study was to examine whether other beta-lactamases, including the Acinetobacter-derived cephalosporinase (ADC), OXA-23, OXA-24/72, and OXA-58 families, also contribute to sulbactam resistance in A. baumannii. The correlation between these beta-lactamases and the sulbactam minimal inhibitory concentration (MIC) was determined using A. baumannii clinical isolates from diverse clonality, which were collected in a nationwide surveillance program from 2002 to 2010 in Taiwan. A possible association between the genetic structure of ISAba1-bla ADC-30 and sulbactam resistance was observed because this genetic structure was detected in 97% of sulbactam-resistant strains compared with 10% of sulbactam-susceptible strains. Transformation of ISAba1-bla ADC-30 into susceptible strains increased the sulbactam MIC from 2 to 32 MUg/ml, which required bla ADC-30 overexpression using an upstream promoter in ISAba1. Flow cytometry showed that ADC-30 production increased in response to sulbactam, ticarcillin, and ceftazidime treatment. This effect was regulated at the RNA level but not by an increase in the bla ADC-30 gene copy number as indicated by quantitative PCR. Purified ADC-30 decreased the inhibitory zone created by sulbactam or ceftazidime, similarly to TEM-1. In conclusion, ADC-30 overexpression conferred resistance to sulbactam in diverse clinical A. baumannii isolates. PMID- 26284031 TI - A reverse-phase protein microarray-based screen identifies host signaling dynamics upon Burkholderia spp. infection. AB - Burkholderia is a diverse genus of gram-negative bacteria that causes high mortality rate in humans, equines and cattle. The lack of effective therapeutic treatments poses serious public health threats. Developing insights toward host Burkholderia spp. interaction is critical for understanding the pathogenesis of infection as well as identifying therapeutic targets for drug development. Reverse-phase protein microarray technology was previously proven to identify and characterize novel biomarkers and molecular signatures associated with infectious disease and cancer. In the present study, this technology was utilized to interrogate changes in host protein expression and phosphorylation events in macrophages infected with a collection of geographically diverse strains of Burkholderia spp. The expression or phosphorylation state of 25 proteins was altered during Burkholderia spp. infections of which eight proteins were selected for further characterization by immunoblotting. Increased phosphorylation of AMPK alpha1, Src, and GSK3beta suggested the importance of their roles in regulating Burkholderia spp. mediated innate immune response. Modulating the inflammatory response by perturbing their activities may provide therapeutic routes for future treatments. PMID- 26284032 TI - The pan-genome as a shared genomic resource: mutual cheating, cooperation and the black queen hypothesis. PMID- 26284033 TI - Prevalences of pathogenic and non-pathogenic Vibrio parahaemolyticus in mollusks from the Spanish Mediterranean Coast. AB - Vibrio parahaemolyticus is a well-recognized pathogen of humans. To better understand the ecology of the human-pathogenic variants of this bacterium in the environment, a study on the prevalence in bivalves of pathogenic variants (tlh+ and tdh+ and/or trh+) versus a non-pathogenic one (only tlh+ as species marker for V. parahaemolyticus), was performed in two bays in Catalonia, Spain. Environmental factors that might affect dynamics of both variants of V. parahaemolyticus were taken into account. The results showed that the global prevalence of total V. parahaemolyticus found in both bays was 14.2% (207/1459). It was, however, significantly dependent on sampling point, campaign (year) and bivalve species. Pathogenic variants of V. parahaemolyticus (tdh+ and/or trh+) were detected in 3.8% of the samples (56/1459), meaning that the proportion of bivalves who contained tlh gene were contaminated by pathogenic V. parahaemolyticus strains is 27.1% (56/207). Moreover, the presence of pathogenic V. parahaemolyticus (trh+) was significantly correlated with water salinity, thus the probability of finding pathogenic V. parahaemolyticus decreased 1.45 times with every salinity unit (ppt) increased. Additionally, data showed that V. parahaemolyticus could establish close associations with Ruditapes spp. (P-value < 0.001), which could enhance the transmission of illness to human by pathogenic variants, when clams were eaten raw or slightly cooked. This study provides information on the abundance, ecology and characteristics of total and human pathogenic V. parahaemolyticus variants associated with bivalves cultured in the Spanish Mediterranean Coast. PMID- 26284034 TI - Culturable diversity and antimicrobial activity of Actinobacteria from marine sediments in Valparaiso bay, Chile. AB - Marine-derived Actinobacteria are a source of a broad variety of secondary metabolites with diverse biological activities, such as antibiotics and antitumorals; many of which have been developed for clinical use. Rare Actinobacteria represent an untapped source of new bioactive compounds that have been scarcely recognized. In this study, rare Actinobacteria from marine sediments were isolated from the Valparaiso bay, Chile, and their potential to produce antibacterial compounds was evaluated. Different culture conditions and selective media that select the growth of Actinobacteria were used leading to the isolation of 68 bacterial strains. Comparative analysis of the 16S rRNA gene sequences led to identifying isolates that belong to the phylum Actinobacteria with genetic affiliations to 17 genera: Aeromicrobium, Agrococcus, Arthrobacter, Brachybacterium, Corynebacterium, Dietzia, Flaviflexus, Gordonia, Isoptericola, Janibacter, Microbacterium, Mycobacterium, Ornithinimicrobium, Pseudonocardia, Rhodococcus, Streptomyces, and Tessaracoccus. Also, one isolate could not be consistently classified and formed a novel phylogenetic branch related to the Nocardiopsaceae family. The antimicrobial activity of these isolates was evaluated, demonstrating the capability of specific novel isolates to inhibit the growth of Gram-positive and Gram-negative bacteria. In conclusion, this study shows a rich biodiversity of culturable Actinobacteria, associated to marine sediments from Valparaiso bay, highlighting novel rare Actinobacteria, and their potential for the production of biologically active compounds. PMID- 26284035 TI - Microbial community changes along the active seepage site of one cold seep in the Red Sea. AB - The active seepage of the marine cold seeps could be a critical process for the exchange of energy between the submerged geosphere and the sea floor environment through organic-rich fluids, potentially even affecting surrounding microbial habitats. However, few studies have investigated the associated microbial community changes. In the present study, 16S rRNA genes were pyrosequenced to decipher changes in the microbial communities from the Thuwal seepage point in the Red Sea to nearby marine sediments in the brine pool, normal marine sediments and water, and benthic microbial mats. An unexpected number of reads from unclassified groups were detected in these habitats; however, the ecological functions of these groups remain unresolved. Furthermore, ammonia-oxidizing archaeal community structures were investigated using the ammonia monooxygenase subunit A (amoA) gene. Analysis of amoA showed that planktonic marine habitats, including seeps and marine water, hosted archaeal ammonia oxidizers that differed from those in microbial mats and marine sediments, suggesting modifications of the ammonia oxidizing archaeal (AOA) communities along the environmental gradient from active seepage sites to peripheral areas. Changes in the microbial community structure of AOA in different habitats (water vs. sediment) potentially correlated with changes in salinity and oxygen concentrations. Overall, the present results revealed for the first time unanticipated novel microbial groups and changes in the ammonia-oxidizing archaea in response to environmental gradients near the active seepages of a cold seep. PMID- 26284038 TI - Denitrifying and diazotrophic community responses to artificial warming in permafrost and tallgrass prairie soils. AB - Increasing temperatures have been shown to impact soil biogeochemical processes, although the corresponding changes to the underlying microbial functional communities are not well understood. Alterations in the nitrogen (N) cycling functional component are particularly important as N availability can affect microbial decomposition rates of soil organic matter and influence plant productivity. To assess changes in the microbial component responsible for these changes, the composition of the N-fixing (nifH), and denitrifying (nirS, nirK, nosZ) soil microbial communities was assessed by targeted pyrosequencing of functional genes involved in N cycling in two major biomes where the experimental effect of climate warming is under investigation, a tallgrass prairie in Oklahoma (OK) and the active layer above permafrost in Alaska (AK). Raw reads were processed for quality, translated with frameshift correction, and a total of 313,842 amino acid sequences were clustered and linked to a nearest neighbor using reference datasets. The number of OTUs recovered ranged from 231 (NifH) to 862 (NirK). The N functional microbial communities of the prairie, which had experienced a decade of experimental warming were the most affected with changes in the richness and/or overall structure of NifH, NirS, NirK and NosZ. In contrast, the AK permafrost communities, which had experienced only 1 year of warming, showed decreased richness and a structural change only with the nirK harboring bacterial community. A highly divergent nirK-harboring bacterial community was identified in the permafrost soils, suggesting much novelty, while other N functional communities exhibited similar relatedness to the reference databases, regardless of site. Prairie and permafrost soils also harbored highly divergent communities due mostly to differing major populations. PMID- 26284037 TI - Link between capacity for current production and syntrophic growth in Geobacter species. AB - Electrodes are unnatural electron acceptors, and it is yet unknown how some Geobacter species evolved to use electrodes as terminal electron acceptors. Analysis of different Geobacter species revealed that they varied in their capacity for current production. Geobacter metallireducens and G. hydrogenophilus generated high current densities (ca. 0.2 mA/cm(2)), comparable to G. sulfurreducens. G. bremensis, G. chapellei, G. humireducens, and G. uraniireducens, produced much lower currents (ca. 0.05 mA/cm(2)) and G. bemidjiensis was previously found to not produce current. There was no correspondence between the effectiveness of current generation and Fe(III) oxide reduction rates. Some high-current-density strains (G. metallireducens and G. hydrogenophilus) reduced Fe(III)-oxides as fast as some low-current-density strains (G. bremensis, G. humireducens, and G. uraniireducens) whereas other low current-density strains (G. bemidjiensis and G. chapellei) reduced Fe(III) oxide as slowly as G. sulfurreducens, a high-current-density strain. However, there was a correspondence between the ability to produce higher currents and the ability to grow syntrophically. G. hydrogenophilus was found to grow in co-culture with Methanosarcina barkeri, which is capable of direct interspecies electron transfer (DIET), but not with Methanospirillum hungatei capable only of H2 or formate transfer. Conductive granular activated carbon (GAC) stimulated metabolism of the G. hydrogenophilus - M. barkeri co-culture, consistent with electron exchange via DIET. These findings, coupled with the previous finding that G. metallireducens and G. sulfurreducens are also capable of DIET, suggest that evolution to optimize DIET has fortuitously conferred the capability for high-density current production to some Geobacter species. PMID- 26284039 TI - DJ1 expression downregulates in neuroblastoma cells (SK-N-MC) chronically exposed to HIV-1 and cocaine. AB - BACKGROUND: HIV-associated neurological disorder (HAND) has long been recognized as a consequence of human immunodeficiency virus (HIV) infection in the brain. The pathology of HAND gets more complicated with the recreational drug use such as cocaine. Recent studies have suggested multiple genetic influences involved in the pathology of addiction and HAND but only a fraction of the entire genetic risk has been investigated so far. In this regard, role of DJ1 protein (a gene linked to autosomal recessive early-onset Parkinson's disease) in regulating dopamine (DA) transmission and reactive oxygen species (ROS) production in neuronal cells will be worth investigating in HIV-1 and cocaine exposed microenvironment. Being a very abundant protein in the brain, DJ1 could serve as a potential marker for early detection of HIV-1 and/or cocaine related neurological disorder. METHODS: In vitro analysis was done to observe the effect of HIV-1 and/or cocaine on DJ1 protein expression in neuroblastoma cells (SK-N MC). Gene and protein expression analysis of DJ1 was done on the HIV infected and/or cocaine treated SK-N-MC and compared to untreated cells using real time PCR, Western Blot and flow cytometry. Effect of DJ1 dysregulation on oxidative stress was analyzed by measuring ROS production in these cells. RESULTS: Gene expression and protein analysis indicated that there was a significant decrease in DJ1 expression in SK-N-MC chronically exposed to HIV-1 and/or cocaine which is inversely proportional to ROS production. CONCLUSION: This is the first study to establish that DJ1 expression level in the neuronal cells significantly decreased in presence of HIV-1 and/or cocaine indicating oxidative stress level of DA neurons. PMID- 26284040 TI - Repurposing celecoxib as a topical antimicrobial agent. AB - There is an urgent need for new antibiotics and alternative strategies to combat multidrug-resistant bacterial pathogens, which are a growing clinical issue. Repurposing existing approved drugs with known pharmacology and toxicology is an alternative strategy to accelerate antimicrobial research and development. In this study, we show that celecoxib, a marketed inhibitor of cyclooxygenase-2, exhibits broad-spectrum antimicrobial activity against Gram-positive pathogens from a variety of genera, including Staphylococcus, Streptococcus, Listeria, Bacillus, and Mycobacterium, but not against Gram-negative pathogens. However, celecoxib is active against all of the Gram-negative bacteria tested, including strains of, Acinetobacter, and Pseudomonas, when their intrinsic resistance is artificially compromised by outer membrane permeabilizing agents such as colistin. The effect of celecoxib on incorporation of radioactive precursors into macromolecules in Staphylococcus aureus was examined. The primary antimicrobial mechanism of action of celecoxib was the dose-dependent inhibition of RNA, DNA, and protein synthesis. Further, we demonstrate the in vivo efficacy of celecoxib in a methicillin-resistant S. aureus (MRSA) infected Caenorhabditis elegans whole animal model. Topical application of celecoxib (1 and 2%) significantly reduced the mean bacterial count in a mouse model of MRSA skin infection. Further, celecoxib decreased the levels of all inflammatory cytokines tested, including tumor necrosis factor-alpha, interleukin-6, interleukin-1 beta, and monocyte chemo attractant protein-1 in wounds caused by MRSA infection. Celecoxib also exhibited synergy with many conventional antimicrobials when tested against four clinical isolates of S. aureus. Collectively, these results demonstrate that celecoxib alone, or in combination with traditional antimicrobials, has a potential to use as a topical drug for the treatment of bacterial skin infections. PMID- 26284036 TI - NADPH-generating systems in bacteria and archaea. AB - Reduced nicotinamide adenine dinucleotide phosphate (NADPH) is an essential electron donor in all organisms. It provides the reducing power that drives numerous anabolic reactions, including those responsible for the biosynthesis of all major cell components and many products in biotechnology. The efficient synthesis of many of these products, however, is limited by the rate of NADPH regeneration. Hence, a thorough understanding of the reactions involved in the generation of NADPH is required to increase its turnover through rational strain improvement. Traditionally, the main engineering targets for increasing NADPH availability have included the dehydrogenase reactions of the oxidative pentose phosphate pathway and the isocitrate dehydrogenase step of the tricarboxylic acid (TCA) cycle. However, the importance of alternative NADPH-generating reactions has recently become evident. In the current review, the major canonical and non canonical reactions involved in the production and regeneration of NADPH in prokaryotes are described, and their key enzymes are discussed. In addition, an overview of how different enzymes have been applied to increase NADPH availability and thereby enhance productivity is provided. PMID- 26284041 TI - Regulation of oxidative stress resistance in Campylobacter jejuni, a microaerophilic foodborne pathogen. AB - Campylobacter jejuni is one of the leading bacterial causes of human gastroenteritis. Due to the increasing rates of human campylobacteriosis, C. jejuni is considered as a serious public health concern worldwide. C. jejuni is a microaerophilic, fastidious bacterium. C. jejuni must overcome a wide range of stress conditions during foodborne transmission to humans, such as food preservation and processing conditions, and even in infection of the gastrointestinal tracts of humans. Particularly, this microaerophilic foodborne pathogen must survive in the atmospheric conditions prior to the initiation of infection. C. jejuni possesses unique regulatory mechanisms for oxidative stress resistance. Lacking OxyR and SoxRS that are highly conserved in other Gram negative foodborne pathogens, C. jejuni modulates the expression of genes involved in oxidative stress resistance mainly via the peroxide resistance regulator and Campylobacter oxidative stress regulator. Based on recent findings of ours and others, in this review, we described how C. jejuni regulates the expression of oxidative stress defense. PMID- 26284043 TI - Isoeugenol has a non-disruptive detergent-like mechanism of action. AB - Isoeugenol is an essential oil constituent of nutmeg, clove, and cinnamon. Despite isoeugenol's promising antimicrobial activity, no studies have yet investigated its mode of antibacterial action at the molecular level. The aim of this study is to clarify isoeugenol's antibacterial mode of action using the Gram negative and Gram-positive model organisms Escherichia coli and Listeria innocua, respectively. We determined the antimicrobial activity of isoeugenol against the model organisms, and examined how isoeugenol affects cell morphology, cell membrane permeabilization, and how isoeugenol interacts with phospholipid membranes using vesicle and supported lipid bilayer models. Isoeugenol demonstrated a bactericidal activity against E. coli and L. innocua that did not affect cell morphology, although the cell membrane was permeabilized. We hypothesized that the cell membrane was the primary site of action, and studied this interaction in further detail using purified membrane model systems. Isoeugenol's permeabilization of calcein-encapsulated vesicles was concentration dependent, and isoeugenol's interaction with giant unilamellar vesicles indicated increased membrane fluidity and a non-disruptive permeabilization mechanism. This contradicted membrane fluidity measurements on supported lipid bilayers (SLBs), which indicated decreased membrane fluidity. However, further investigations demonstrated that the interaction between isoeugenol and bilayers was reversible, and caused membranes to display heterogeneous topography, an increased mass, and a higher degree of hydration. In conclusion, we propose that isoeugenol interacts with membranes in a reversible non-disruptive detergent-like manner, which causes membrane destabilization. Furthermore, we argue that isoeugenol increases membrane fluidity. Our work contributes to the understanding of how essential oil constituents interact with cell components. PMID- 26284042 TI - Rational engineering of Geobacter sulfurreducens electron transfer components: a foundation for building improved Geobacter-based bioelectrochemical technologies. AB - Multiheme cytochromes have been implicated in Geobacter sulfurreducens extracellular electron transfer (EET). These proteins are potential targets to improve EET and enhance bioremediation and electrical current production by G. sulfurreducens. However, the functional characterization of multiheme cytochromes is particularly complex due to the co-existence of several microstates in solution, connecting the fully reduced and fully oxidized states. Over the last decade, new strategies have been developed to characterize multiheme redox proteins functionally and structurally. These strategies were used to reveal the functional mechanism of G. sulfurreducens multiheme cytochromes and also to identify key residues in these proteins for EET. In previous studies, we set the foundations for enhancement of the EET abilities of G. sulfurreducens by characterizing a family of five triheme cytochromes (PpcA-E). These periplasmic cytochromes are implicated in electron transfer between the oxidative reactions of metabolism in the cytoplasm and the reduction of extracellular terminal electron acceptors at the cell's outer surface. The results obtained suggested that PpcA can couple e(-)/H(+) transfer, a property that might contribute to the proton electrochemical gradient across the cytoplasmic membrane for metabolic energy production. The structural and functional properties of PpcA were characterized in detail and used for rational design of a family of 23 single site PpcA mutants. In this review, we summarize the functional characterization of the native and mutant proteins. Mutants that retain the mechanistic features of PpcA and adopt preferential e(-)/H(+) transfer pathways at lower reduction potential values compared to the wild-type protein were selected for in vivo studies as the best candidates to increase the electron transfer rate of G. sulfurreducens. For the first time G. sulfurreducens strains have been manipulated by the introduction of mutant forms of essential proteins with the aim to develop and improve bioelectrochemical technologies. PMID- 26284044 TI - Chromosome replication, cell growth, division and shape: a personal perspective. AB - The origins of Molecular Biology and Bacterial Physiology are reviewed, from our personal standpoints, emphasizing the coupling between bacterial growth, chromosome replication and cell division, dimensions and shape. Current knowledge is discussed with historical perspective, summarizing past and present achievements and enlightening ideas for future studies. An interactive simulation program of the bacterial cell division cycle (BCD), described as "The Central Dogma in Bacteriology," is briefly represented. The coupled process of transcription/translation of genes encoding membrane proteins and insertion into the membrane (so-called transertion) is invoked as the functional relationship between the only two unique macromolecules in the cell, DNA and peptidoglycan embodying the nucleoid and the sacculus respectively. We envision that the total amount of DNA associated with the replication terminus, so called "nucleoid complexity," is directly related to cell size and shape through the transertion process. Accordingly, the primary signal for cell division transmitted by DNA dynamics (replication, transcription and segregation) to the peptidoglycan biosynthetic machinery is of a physico-chemical nature, e.g., stress in the plasma membrane, relieving nucleoid occlusion in the cell's center hence enabling the divisome to assemble and function between segregated daughter nucleoids. PMID- 26284045 TI - Assessing the function of STAS domain protein SypA in Vibrio fischeri using a comparative analysis. AB - Colonization of the squid Euprymna scolopes by Vibrio fischeri requires biofilm formation dependent on the 18-gene symbiosis polysaccharide locus, syp. One key regulator, SypA, controls biofilm formation by an as-yet unknown mechanism; however, it is known that SypA itself is regulated by SypE. Biofilm-proficient strains form wrinkled colonies on solid media, while sypA mutants form biofilm defective smooth colonies. To begin to understand the function of SypA, we used comparative analyses and mutagenesis approaches. sypA (and the syp locus) is conserved in other Vibrios, including two food-borne human pathogens, Vibrio vulnificus (rbdA) and Vibrio parahaemolyticus (sypA VP ). We found that both homologs could complement the biofilm defect of the V. fischeri sypA mutant, but their phenotypes varied depending on the biofilm-inducing conditions used. Furthermore, while SypAVP retained an ability to be regulated by SypE, RbdA was resistant to this control. To better understand SypA function, we examined the biofilm-promoting ability of a number of mutant SypA proteins with substitutions in conserved residues, and found many that were biofilm-defective. The most severe biofilm-defective phenotypes occurred when changes were made to a conserved stretch of amino acids within a predicted alpha-helix of SypA; we hypothesize that this region of SypA may interact with another protein to promote biofilm formation. Finally, we identified a residue required for negative control by SypE. Together, our data provide insights into the function of this key biofilm regulator and suggest that the SypA orthologs may play similar roles in their native Vibrio species. PMID- 26284046 TI - Decoding the genetic and functional diversity of the DSF quorum-sensing system in Stenotrophomonas maltophilia. AB - Stenotrophomonas maltophilia uses the Diffusible Signal Factor (DSF) quorum sensing (QS) system to mediate intra- and inter-specific signaling and regulate virulence-related processes. The components of this system are encoded by the rpf cluster, with genes rpfF and rpfC encoding for the DSF synthase RpfF and sensor RpfC, respectively. Recently, we have shown that there exist two variants of the rpf cluster (rpf-1 and rpf-2), distinguishing two groups of S. maltophilia strains. Surprisingly, only rpf-1 strains produce detectable DSF, correlating with their ability to control biofilm formation, swarming motility and virulence. The evolutive advantage of acquiring two different rpf clusters, the phylogenetic time point and mechanism of this acquisition and the conditions that activate DSF production in rpf-2 strains, are however not known. Examination of this cluster in various species suggests that its variability originated most probably by genetic exchange between rhizosphere bacteria. We propose that rpf-2 variant strains make use of a strategy recently termed as "social cheating." Analysis of cellular and extracellular fatty acids (FAs) of strains E77 (rpf-1) and M30 (rpf 2) suggests that their RpfFs have also a thioesterase activity that facilitates the release of unspecific FAs to the medium in addition to DSF. Production of DSF in rpf-1 strains appears in fact to be modulated by some of these extracellular FAs in addition to other factors such as temperature and nutrients, while in rpf 2 strains DSF biosynthesis is derepressed only upon detection of DSF itself, suggesting that they require cohabitation with DSF-producer bacteria to activate their DSF regulatory machinery. Finally, we show that the mixed rpf-1/rpf-2 population presents synergism in DSF production and virulence capacity in an in vivo infection model. Recovery and quantification of DSF from co-infected animals correlates with the observed mortality rate. PMID- 26284047 TI - Reutericyclin producing Lactobacillus reuteri modulates development of fecal microbiota in weanling pigs. AB - Lactobacillus reuteri is used as probiotic culture in food and feed applications; however, strain specific properties of L. reuteri that mediate probiotic activity remain unknown. This study aimed to determine effects of feed fermentation with exopolysaccharide and reutericyclin producing L. reuteri on the transition of the gut microbiome of piglets after weaning. The reutericyclin and reuteran producing L. reuteri TMW1.656 was compared to the reutericyclin negative and levan producing L. reuteri LTH5794 and unfermented controls. Both strains were fermented at conditions supporting exopolysaccharide formation, or at conditions not supporting exopolysaccharide formation. Fecal microbiota were characterized by partial sequencing of 16S rRNA genes, and by quantitative PCR targeting clostridial toxins. The transition to solid food resulted in a transient increase of Proteobacteria to 12% of total bacteria, and increased bacterial diversity by increasing the abundance of anaerobic fiber fermenting Firmicutes. Three weeks after weaning, Prevotella and Lactobacillus were among the dominant bacterial genera. Feed fermentation with L. reuteri affected the abundance of few bacterial taxa and particularly reduced the abundance of Enterobacteriaceae (P < 0.05) when compared to unfermented controls. Reutericyclin producing L. reuteri increased the abundance of Dialister spp. and Mitsuokella spp. (P < 0.05) but did not influence the abundance of clostridial toxins in the feces. In conclusion, data on the contribution of specific metabolic activities of L. reuteri to probiotic activity will facilitate the strain selection for probiotic applications in food and feed. PMID- 26284048 TI - Identification of iron and heme utilization genes in Aeromonas and their role in the colonization of the leech digestive tract. AB - It is known that many pathogens produce high-affinity iron uptake systems like siderophores and/or proteins for utilizing iron bound to heme-containing molecules, which facilitate iron-acquisition inside a host. In mutualistic digestive-tract associations, iron uptake systems have not been as well studied. We investigated the importance of two iron utilization systems within the beneficial digestive-tract association Aeromonas veronii and the medicinal leech, Hirudo verbana. Siderophores were detected in A. veronii using chrome azurol S. Using a mini Tn5, a transposon insertion in viuB generated a mutant unable to utilize iron using siderophores. The A. veronii genome was then searched for genes potentially involved in iron utilization bound to heme-containing molecules. A putative outer membrane heme receptor (hgpB) was identified with a transcriptional activator, termed hgpR, downstream. The hgpB gene was interrupted with an antibiotic resistance cassette in both the parent strain and the viuB mutant, yielding an hgpB mutant and a mutant with both iron uptake systems inactivated. In vitro assays indicated that hgpB is involved in utilizing iron bound to heme and that both iron utilization systems are important for A. veronii to grow in blood. In vivo colonization assays revealed that the ability to acquire iron from heme-containing molecules is critical for A. veronii to colonize the leech gut. Since iron and specifically heme utilization is important in this mutualistic relationship and has a potential role in virulence factor of other organisms, genomes from different Aeromonas strains (both clinical and environmental) were queried with iron utilization genes of A. veronii. This analysis revealed that in contrast to the siderophore utilization genes heme utilization genes are widely distributed among aeromonads. The importance of heme utilization in the colonization of the leech further confirms that symbiotic and pathogenic relationships possess similar mechanisms for interacting with animal hosts. PMID- 26284049 TI - Why do bacteria regulate public goods by quorum sensing?-How the shapes of cost and benefit functions determine the form of optimal regulation. AB - Many bacteria secrete compounds which act as public goods. Such compounds are often under quorum sensing (QS) regulation, yet it is not understood exactly when bacteria may gain from having a public good under QS regulation. Here, we show that the optimal public good production rate per cell as a function of population size (the optimal production curve, OPC) depends crucially on the cost and benefit functions of the public good and that the OPC will fall into one of two categories: Either it is continuous or it jumps from zero discontinuously at a critical population size. If, e.g., the public good has accelerating returns and linear cost, then the OPC is discontinuous and the best strategy thus to ramp up production sharply at a precise population size. By using the example of public goods with accelerating and diminishing returns (and linear cost) we are able to determine how the two different categories of OPSs can best be matched by production regulated through a QS signal feeding back on its own production. We find that the optimal QS parameters are different for the two categories and specifically that public goods which provide accelerating returns, call for stronger positive signal feedback. PMID- 26284050 TI - A PAS domain-containing regulator controls flagella-flagella interactions in Campylobacter jejuni. AB - The bipolar flagella of the foodborne bacterial pathogen Campylobacter jejuni confer motility, which is essential for virulence. The flagella of C. jejuni are post-translationally modified, but how this process is controlled is not well understood. In this work, we have identified a novel PAS-domain containing regulatory system, which modulates flagella-flagella interactions in C. jejuni. Inactivation of the cj1387c gene, encoding a YheO-like PAS6 domain linked to a helix-turn-helix domain, resulted in the generation of a tightly associated "cell train" morphotype, where up to four cells were connected by their flagella. The morphotype was fully motile, resistant to vortexing, accompanied by increased autoagglutination, and was not observed in aflagellated cells. The Deltacj1387c mutant displayed increased expression of the adjacent Cj1388 protein, which comprises of a single endoribonuclease L-PSP domain. Comparative genomics showed that cj1387c (yheO) orthologs in bacterial genomes are commonly linked to an adjacent cj1388 ortholog, with some bacteria, including C. jejuni, containing another cj1388-like gene (cj0327). Inactivation of the cj1388 and cj0327 genes resulted in decreased autoagglutination in Tween-20-supplemented media. The Deltacj1388 and Deltacj0327 mutants were also attenuated in a Galleria larvae based infection model. Finally, substituting the sole cysteine in Cj1388 for serine prevented Cj1388 dimerization in non-reducing conditions, and resulted in decreased autoagglutination in the presence of Tween-20. We hypothesize that Cj1388 and Cj0327 modulate post-translational modification of the flagella through yet unidentified mechanisms, and propose naming Cj1387 the Campylobacter Flagella Interaction Regulator CfiR, and the Cj1388 and Cj0327 protein as CfiP and CfiQ, respectively. PMID- 26284051 TI - The PadR-like transcriptional regulator LftR ensures efficient invasion of Listeria monocytogenes into human host cells. AB - Invasion of the bacterial pathogen Listeria monocytogenes into human host cells requires specialized surface molecules for attachment and induction of phagocytosis. However, efficient invasion is also dependent on factors with house keeping functions, such as SecA2-dependent secretion of autolysins for post divisional segregation of daughter cells. Mutations in this pathway prevent degradation of peptidoglycan cross-walls, so that long cell chains are formed that cannot be phagocytosed. The extreme chaining of such mutants manifests as rough colony phenotype. One rough clone was isolated from a transposon library with a transposon insertion in the uncharacterized lmo0720 gene (lftS) together with a spontaneous point mutation in the secA2 gene. We separated both mutations and demonstrated that this point mutation in the intramolecular regulator 2 domain of SecA2 was sufficient to inactivate the protein. In contrast, lftS deletion did not cause a DeltasecA2-like phenotype. lftS is located in an operon with lftR (lmo0719), encoding a PadR-like transcriptional regulator, and lftR deletion affected growth, invasion and day-light dependent coordination of swarming. Inactivation of lftS partially suppressed these phenotypes, suggesting a functional relationship between LftR and LftS. However, the invasion defect of the DeltalftR mutant was only marginally suppressed by lftS removal. LftR regulates expression of the lmo0979-0980 (lieAB) operon, encoding a putative multidrug resistance transporter and lieAB transcription was strongly upregulated in the absence of LftR. Deletion of lieAB in the DeltalftR background restores wild type-like invasion levels. Hence, we conclude that tight transcriptional repression of the lieAB operon is essential for efficient listerial host cell invasion. PMID- 26284052 TI - Hha has a defined regulatory role that is not dependent upon H-NS or StpA. AB - The Hha family of proteins is involved in the regulation of gene expression in enterobacteria by forming complexes with H-NS-like proteins. Whereas several amino acid residues of both proteins participate in the interaction, some of them play a key role. Residue D48 of Hha protein is essential for the interaction with H-NS, thus the D48N substitution in Hha protein abrogates H-NS/Hha interaction. Despite being a paralog of H-NS protein, StpA interacts with HhaD48N with higher affinity than with the wild type Hha protein. To analyze whether Hha is capable of acting independently of H-NS and StpA, we conducted transcriptomic analysis on the hha and stpA deletion strains and the hhaD48N substitution strain of Salmonella Typhimurium using a custom microarray. The results obtained allowed the identification of 120 genes regulated by Hha in an H-NS/StpA-independent manner, 38% of which are horizontally acquired genes. A significant number of the identified genes are involved in functions related to cell motility, iron uptake, and pathogenicity. Thus, motility assays, siderophore detection and intra macrophage replication assays were performed to confirm the transcriptomic data. Our findings point out the importance of Hha protein as an independent regulator in S. Typhimurium, highlighting a regulatory role on virulence. PMID- 26284053 TI - Synthetic biology of fungal natural products. AB - Synthetic biology is an ever-expanding field in science, also encompassing the research area of fungal natural product (NP) discovery and production. Until now, different aspects of synthetic biology have been covered in fungal NP studies from the manipulation of different regulatory elements and heterologous expression of biosynthetic pathways to the engineering of different multidomain biosynthetic enzymes such as polyketide synthases or non-ribosomal peptide synthetases. The following review will cover some of the exemplary studies of synthetic biology in filamentous fungi showing the capacity of these eukaryotes to be used as model organisms in the field. From the vast array of different NPs produced to the ease for genetic manipulation, filamentous fungi have proven to be an invaluable source for the further development of synthetic biology tools. PMID- 26284055 TI - MBL-2 polymorphisms (codon 54 and Y-221X) and low MBL levels are associated with susceptibility to multi organ dysfunction in P. falciparum malaria in Odisha, India. AB - BACKGROUND: Mannose binding lectin, a plasma protein protects host from virus, bacteria, and parasites. Deficiency in MBL levels has been associated with susceptibility to various infectious diseases including P. falciparum malaria. Common MBL polymorphisms in promoter and coding regions are associated with decrease in plasma MBL levels or production of deformed MBL, respectively. In the present study, we hypothesized that MBL2 variants and plasma MBL levels could be associated with different clinical phenotypes of severe P. falciparum malaria. METHODS: A hospital based study was conducted in eastern Odisha, India which is endemic to P. falciparum malaria. Common MBL-2 polymorphisms (codon 54, H-550L, and Y-221X) were typed in 336 cases of severe malaria (SM) [94 cerebral malaria (CM), 120 multi-organ dysfunction (MOD), 122 non-cerebral severe malaria (NCSM)] and 131 un-complicated malaria patients (UM). Plasma MBL levels were quantified by ELISA. RESULTS: Severe malaria patients displayed lower plasma levels of MBL compared to uncomplicated falciparum malaria. Furthermore, on categorization of severe malaria patients into various subtypes, plasma MBL levels were very low in MOD patients compared to other categories. Higher frequency of AB genotype and allele B was observed in MOD compared to UM (AB genotype: P = 0.006; B allele: P = 0.008). In addition, prevalence of YX genotype of MBL Y-221X polymorphism was also statistically more frequent in MOD case than UM (P = 0.009). CONCLUSIONS: The observations of the present study reveal that MBL-2 polymorphisms (codon 54 and Y-221X) and lower plasma MBL levels are associated with increased susceptibility to multi organ dysfunctions in P. falciparum malaria. PMID- 26284056 TI - Forest-to-pasture conversion increases the diversity of the phylum Verrucomicrobia in Amazon rainforest soils. AB - The Amazon rainforest is well known for its rich plant and animal diversity, but its bacterial diversity is virtually unexplored. Due to ongoing and widespread deforestation followed by conversion to agriculture, there is an urgent need to quantify the soil biological diversity within this tropical ecosystem. Given the abundance of the phylum Verrucomicrobia in soils, we targeted this group to examine its response to forest-to-pasture conversion. Both taxonomic and phylogenetic diversities were higher for pasture in comparison to primary and secondary forests. The community composition of Verrucomicrobia in pasture soils was significantly different from those of forests, with a 11.6% increase in the number of sequences belonging to subphylum 3 and a proportional decrease in sequences belonging to the class Spartobacteria. Based on 99% operational taxonomic unit identity, 40% of the sequences have not been detected in previous studies, underscoring the limited knowledge regarding the diversity of microorganisms in tropical ecosystems. The abundance of Verrucomicrobia, measured with quantitative PCR, was strongly correlated with soil C content (r = 0.80, P = 0.0016), indicating their importance in metabolizing plant-derived carbon compounds in soils. PMID- 26284054 TI - Toward the identification of methanogenic archaeal groups as targets of methane mitigation in livestock animalsr. AB - In herbivores, enteric methane is a by-product from the digestion of plant biomass by mutualistic gastrointestinal tract (GIT) microbial communities. Methane is a potent greenhouse gas that is not assimilated by the host and is released into the environment where it contributes to climate change. Since enteric methane is exclusively produced by methanogenic archaea, the investigation of mutualistic methanogen communities in the GIT of herbivores has been the subject of ongoing research by a number of research groups. In an effort to uncover trends that would facilitate the development of efficient methane mitigation strategies for livestock species, we have in this review summarized and compared currently available results from published studies on this subject. We also offer our perspectives on the importance of pursuing current research efforts on the sequencing of gut methanogen genomes, as well as investigating their cellular physiology and interactions with other GIT microorganisms. PMID- 26284057 TI - Biocontrol mechanism by root-associated Bacillus amyloliquefaciens FZB42 - a review. AB - Bacillus amyloliquefaciens subsp. plantarum FZB42 is a Gram-positive model bacterium for unraveling plant-microbe interactions in Bacilli. In addition, FZB42 is used commercially as biofertilizer and biocontrol agent in agriculture. Genome analysis of FZB42 revealed that nearly 10% of the FZB42 genome is devoted to synthesizing antimicrobial metabolites and their corresponding immunity genes. However, recent investigations in planta demonstrated that - except surfactin - the amount of such compounds found in vicinity of plant roots is relatively low, making doubtful a direct function in suppressing competing microflora including plant pathogens. These metabolites have been also suspected to induce changes within the rhizosphere microbial community, which might affect environment and plant health. However, sequence analysis of rhizosphere samples revealed only marginal changes in the root microbiome, suggesting that secondary metabolites are not the key factor in protecting plants from pathogenic microorganisms. On the other hand, adding FZB42 to plants compensate, at least in part, changes in the community structure caused by the pathogen, indicating an interesting mechanism of plant protection by beneficial Bacilli. Sub-lethal concentrations of cyclic lipopeptides and volatiles produced by plant-associated Bacilli trigger pathways of induced systemic resistance (ISR), which protect plants against attacks of pathogenic microbes, viruses, and nematodes. Stimulation of ISR by bacterial metabolites is likely the main mechanism responsible for biocontrol action of FZB42. PMID- 26284058 TI - Associative patterns among anaerobic fungi, methanogenic archaea, and bacterial communities in response to changes in diet and age in the rumen of dairy cows. AB - The rumen microbiome represents a complex microbial genetic web where bacteria, anaerobic rumen fungi (ARF), protozoa and archaea work in harmony contributing to the health and productivity of ruminants. We hypothesized that the rumen microbiome shifts as the dairy cow advances in lactations and these microbial changes may contribute to differences in productivity between primiparous (first lactation) and multiparous (>=second lactation) cows. To this end, we investigated shifts in the ruminal ARF and methanogenic communities in both primiparous (n = 5) and multiparous (n = 5) cows as they transitioned from a high forage to a high grain diet upon initiation of lactation. A total of 20 rumen samples were extracted for genomic DNA, amplified using archaeal and fungal specific primers, sequenced on a 454 platform and analyzed using QIIME. Community comparisons (Bray-Curtis index) revealed the effect of diet (P < 0.01) on ARF composition, while archaeal communities differed between primiparous and multiparous cows (P < 0.05). Among ARF, several lineages were unclassified, however, phylum Neocallimastigomycota showed the presence of three known genera. Abundance of Cyllamyces and Caecomyces shifted with diet, whereas Orpinomyces was influenced by both diet and age. Methanobrevibacter constituted the most dominant archaeal genus across all samples. Co-occurrence analysis incorporating taxa from bacteria, ARF and archaea revealed syntrophic interactions both within and between microbial domains in response to change in diet as well as age of dairy cows. Notably, these interactions were numerous and complex in multiparous cows, supporting our hypothesis that the rumen microbiome also matures with age to sustain the growing metabolic needs of the host. This study provides a broader picture of the ARF and methanogenic populations in the rumen of dairy cows and their co-occurrence implicates specific relationships between different microbial domains in response to diet and age. PMID- 26284059 TI - Antimicrobial activity and the presence of virulence factors and bacteriocin structural genes in Enterococcus faecium CM33 isolated from ewe colostrum. AB - Screening of lactic acid bacteria (LAB) isolated from ewe colostrum led to the identification and isolation of Enterococcus faecium CM33 with interesting features like high survival rates under acidic or bile salts condition, high tolerance for the simulated gastrointestinal condition, and high adhesive potential to Caco-2 cells. According the inhibition of pathogen adhesion test results, this strain can reduce more than 50% adhesion capacity of Escherichia coli, Shigella flexneri, Klebsiella pneumoniae, Listeria monocytogenes, and Staphylococcus aureus to Caco-2 cells. Based on the antibiotic sensitivity test findings, E. faecium CM33 was susceptible to gentamycin, vancomycin, erythromycin, ampicillin, penicillin, tetracycline, and rifampicin, but resistant to chloramphenicol, clindamycin, and kanamycin. Upon assessment of the virulence determinants for E. faecium CM33, this strain was negative for all tested virulence genes. Furthermore, the genome of this strain was evaluated for the incidence of the known enterocin genes by specific PCR amplification and discovered the genes encoding enterocins A, 31, X, and Q. Based on this study findings, the strain E. faecium CM33 can be considered as a valuable nutraceutical and can be introduced as a new potential probiotic. PMID- 26284060 TI - Rational and combinatorial tailoring of bioactive cyclic dipeptides. AB - Modified cyclic dipeptides represent a diverse family of microbial secondary metabolites. They display a broad variety of biological and pharmacological activities and have long been recognized as privileged structures with the ability to bind to a wide range of receptors. This is due to their conformationally constrained 2, 5-diketopiperazine (DKP) scaffold and the diverse set of DKP tailoring enzymes present in nature. After initial DKP assembly through different biosynthetic systems modifying enzymes are responsible for installing functional groups crucial for the biological activities of the resulting modified DKPs. They represent a vast and largely untapped enzyme repository very useful for synthetic biology approaches aiming at introducing structural variations into DKP scaffolds. In this review we focus on these DKP modification enzymes found in various microbial secondary metabolite gene clusters. We will give a brief overview of their distribution and highlight a select number of characterized DKP tailoring enzymes before turning to their application potential in combinatorial biosynthesis with the aim of producing molecules with improved or entirely new biological and medicinally relevant properties. PMID- 26284061 TI - Biogenic concrete protection driven by the formate oxidation by Methylocystis parvus OBBP. AB - The effectiveness of Microbiologically Induced Carbonate Precipitation (MICP) from the formate oxidation by Methylocystis parvus OBBP as an alternative process for concrete protection was investigated. MICP was induced on Autoclaved Aerated Concrete (AAC), the model material, by immersing the material in 10(9) M. parvus cells mL(-1) containing 5 g L(-1) of calcium formate. A 2 days immersion of the material gave the maximum weight increase of the specimens (38 +/- 19 mg) and this was likely due to the deposition of calcium carbonate, biomass, and unconverted calcium formate. The solid deposition mainly occurred in the micropores of the specimen, close to the outer surface. A significantly lower water absorption was observed in the bacterially treated specimens compared to the non-treated ones (up to 2.92 +/- 0.91 kg m(-2)) and this could be attributed to the solid deposition. However, the sonication test demonstrated that the bacterial treatment did not give a consolidating effect to the material. Overall, compared to the currently employed urea hydrolysis process, the formate-based MICP by M. parvus offers a more environmentally friendly approach for the biotechnological application to protect concrete. PMID- 26284062 TI - The Extended Family of CD1d-Restricted NKT Cells: Sifting through a Mixed Bag of TCRs, Antigens, and Functions. AB - Natural killer T (NKT) cells comprise a family of specialized T cells that recognize lipid antigens presented by CD1d. Based on their T cell receptor (TCR) usage and antigen specificities, CD1d-restricted NKT cells have been divided into two main subsets: type I NKT cells that use a canonical invariant TCR alpha-chain and recognize alpha-galactosylceramide (alpha-GalCer), and type II NKT cells that use a more diverse alphabeta TCR repertoire and do not recognize alpha-GalCer. In addition, alpha-GalCer-reactive NKT cells that use non-canonical alphabeta TCRs and CD1d-restricted T cells that use gammadelta or delta/alphabeta TCRs have recently been identified, revealing further diversity among CD1d-restricted T cells. Importantly, in addition to their distinct antigen specificities, functional differences are beginning to emerge between the different members of the CD1d-restricted T cell family. In this review, while using type I NKT cells as comparison, we will focus on type II NKT cells and the other non-invariant CD1d-restricted T cell subsets, and discuss our current understanding of the antigens they recognize, the formation of stimulatory CD1d/antigen complexes, the modes of TCR-mediated antigen recognition, and the mechanisms and consequences of their activation that underlie their function in antimicrobial responses, anti tumor immunity, and autoimmunity. PMID- 26284064 TI - Genetic and Environmental Factors Affecting TNF-alpha Responses in Relation to Sudden Infant Death Syndrome. AB - Dysregulation of the inflammatory responses has been suggested to contribute to the events leading to sudden infant deaths. Our objectives were (1) to analyze a single nucleotide polymorphism (SNP) associated with high levels of tumor necrosis factor-alpha (TNF-alpha) responses, TNF G-308A, in sudden infant death syndrome (SIDS) infants, SIDS and control parents, and ethnic groups with different incidences of SIDS; (2) the effects of two risk factors for SIDS, cigarette smoke and virus infection, on TNF-alpha responses; and (3) to assess effects of genotype, cigarette smoke, and gender on TNF-alpha responses to bacterial toxins identified in SIDS infants. TNF G-308A genotypes were determined by real-time polymerase chain reaction for SIDS infants from Australia, Germany, and Hungary; parents of SIDS infants and their controls; and populations with high (Aboriginal Australian), medium (Caucasian), and low (Bangladeshi) SIDS incidences. Leukocytes from Caucasian donors were stimulated in vitro with endotoxin or toxic shock syndrome toxin-1 (TSST-1). TNF-alpha responses were measured by L929 bioassay (IU/ml) and assessed in relation to genotype, smoking status, and gender. There was a significantly higher proportion of the minor allele AA genotype among Australian SIDS infants (6/24, 24%) compared to 3/62 (4.8%) controls (p = 0.03). There were no significant differences in TNF-alpha responses by TNF G-308A genotypes when assessed in relation to smoking status or gender. Given the rarity of the TNF G-308A A allele in Caucasian populations, the finding that 24% of the Australian SIDS infants tested had this genotype requires further investigation and cautious interpretation. Although non-smokers with the AA genotype had higher TNFalpha responses to both TSST-1 and endotoxin, there were too few subjects with this rare allele to obtain statistically valid results. No effects of genotype, smoking, or gender were observed for TNF-alpha responses to these toxins. PMID- 26284063 TI - NK Cell-Mediated Antibody-Dependent Cellular Cytotoxicity in Cancer Immunotherapy. AB - Natural killer (NK) cells play a major role in cancer immunotherapies that involve tumor-antigen targeting by monoclonal antibodies (mAbs). NK cells express a variety of activating and inhibitory receptors that serve to regulate the function and activity of the cells. In the context of targeting cells, NK cells can be "specifically activated" through certain Fc receptors that are expressed on their cell surface. NK cells can express FcgammaRIIIA and/or FcgammaRIIC, which can bind to the Fc portion of immunoglobulins, transmitting activating signals within NK cells. Once activated through Fc receptors by antibodies bound to target cells, NK cells are able to lyse target cells without priming, and secrete cytokines like interferon gamma to recruit adaptive immune cells. This antibody-dependent cell-mediated cytotoxicity (ADCC) of tumor cells is utilized in the treatment of various cancers overexpressing unique antigens, such as neuroblastoma, breast cancer, B cell lymphoma, and others. NK cells also express a family of receptors called killer immunoglobulin-like receptors (KIRs), which regulate the function and response of NK cells toward target cells through their interaction with their cognate ligands that are expressed on tumor cells. Genetic polymorphisms in KIR and KIR-ligands, as well as FcgammaRs may influence NK cell responsiveness in conjunction with mAb immunotherapies. This review focuses on current therapeutic mAbs, different strategies to augment the anti-tumor efficacy of ADCC, and genotypic factors that may influence patient responses to antibody dependent immunotherapies. PMID- 26284066 TI - An Introduction to Automated Flow Cytometry Gating Tools and Their Implementation. AB - Current flow cytometry (FCM) reagents and instrumentation allow for the measurement of an unprecedented number of parameters for any given cell within a homogenous or heterogeneous population. While this provides a great deal of power for hypothesis testing, it also generates a vast amount of data, which is typically analyzed manually through a processing called "gating." For large experiments, such as high-content screens, in which many parameters are measured, the time required for manual analysis as well as the technical variability inherent to manual gating can increase dramatically, even becoming prohibitive depending on the clinical or research goal. In the following article, we aim to provide the reader an overview of automated FCM analysis as well as an example of the implementation of FLOw Clustering without K, a tool that we consider accessible to researchers of all levels of computational expertise. In most cases, computational assistance methods are more reproducible and much faster than manual gating, and for some, also allow for the discovery of cellular populations that might not be expected or evident to the researcher. We urge any researcher who is planning or has previously performed large FCM experiments to consider implementing computational assistance into their analysis pipeline. PMID- 26284067 TI - Systemic Lupus Erythematosus: Molecular Mimicry between Anti-dsDNA CDR3 Idiotype, Microbial and Self Peptides-As Antigens for Th Cells. AB - Systemic lupus erythematosus (SLE) is marked by a T helper (Th) cell-dependent B cell hyperresponsiveness, with frequent germinal center reactions, and gammaglobulinemia. A feature of SLE is the finding of IgG autoantibodies specific for dsDNA. The specificity of the Th cells that drive the expansion of anti-dsDNA B cells is unresolved. However, anti-microbial, anti-histone, and anti-idiotype Th cell responses have been hypothesized to play a role. It has been entirely unclear if these seemingly disparate Th cell responses and hypotheses could be related or unified. Here, we describe that H chain CDR3 idiotypes from IgG(+) B cells of lupus mice have sequence similarities with both microbial and self peptides. Matched sequences were more frequent within the mutated CDR3 repertoire and when sequences were derived from lupus mice with expanded anti-dsDNA B cells. Analyses of histone sequences showed that particular histone peptides were similar to VDJ junctions. Moreover, lupus mice had Th cell responses toward histone peptides similar to anti-dsDNA CDR3 sequences. The results suggest that Th cells in lupus may have multiple cross-reactive specificities linked to the IgVH CDR3 Id-peptide sequences as well as similar DNA-associated protein motifs. PMID- 26284065 TI - The Role of Invariant Natural Killer T Cells in Dendritic Cell Licensing, Cross Priming, and Memory CD8(+) T Cell Generation. AB - New vaccination strategies focus on achieving CD8(+) T cell (CTL) immunity rather than on induction of protective antibody responses. While the requirement of CD4(+) T (Th) cell help in dendritic cell (DC) activation and licensing, and in CTL memory induction has been described in several disease models, CTL responses may occur in a Th cell help-independent manner. Invariant natural killer T cells (iNKT cells) can substitute for Th cell help and license DC as well. iNKT cells produce a broad spectrum of Th1 and Th2 cytokines, thereby inducing a similar set of costimulatory molecules and cytokines in DC. This form of licensing differs from Th cell help by inducing other chemokines, while Th cell-licensed DCs produce CCR5 ligands, iNKT cell-licensed DCs produce CCL17, which attracts CCR4(+) CD8(+) T cells for subsequent activation. It has recently been shown that iNKT cells do not only enhance immune responses against bacterial pathogens or parasites but also play a role in viral infections. The inclusion of iNKT cell ligands in influenza virus vaccines enhanced memory CTL generation and protective immunity in a mouse model. This review will focus on the role of iNKT cells in the cross-talk with cross-priming DC and memory CD8(+) T cell formation. PMID- 26284068 TI - eIF2alpha Confers Cellular Tolerance to S. aureus alpha-Toxin. AB - We report on the role of conserved stress-response pathways for cellular tolerance to a pore forming toxin. First, we observed that small molecular weight inhibitors including of eIF2alpha-phosphatase, jun-N-terminal kinase (JNK), and PI3-kinase sensitized normal mouse embryonal fibroblasts (MEFs) to the small pore forming S. aureus alpha-toxin. Sensitization depended on expression of mADAM10, the murine ortholog of a proposed high-affinity receptor for alpha-toxin in human cells. Similarly, eIF2alpha (S51A/S51A) MEFs, which harbor an Ala knock-in mutation at the regulated Ser51 phosphorylation site of eukaryotic translation initiation factor 2alpha, were hyper-sensitive to alpha-toxin. Inhibition of translation with cycloheximide did not mimic the tolerogenic effect of eIF2alpha phosphorylation. Notably, eIF2alpha-dependent tolerance of MEFs was toxin selective, as wild-type MEFs and eIF2alpha (S51A/S51A) MEFs exhibited virtually equal sensitivity to Vibrio cholerae cytolysin. Binding of S. aureus alpha-toxin to eIF2alpha (S51A/S51A) MEFs and toxicity in these cells were enhanced as compared to wild-type cells. This led to the unexpected finding that the mutant cells carried more ADAM10. Because basal phosphorylation of eIF2alpha in MEFs required amino acid deprivation-activated eIF2alpha-kinase 4/GCN2, the data reveal that basal activity of this kinase mediates tolerance of MEFs to alpha toxin. Further, they suggest that modulation of ADAM10 is involved. During infection, bacterial growth may cause nutrient shortage in tissues, which might activate this response. Tolerance to alpha-toxin was robust in macrophages and did not depend on GCN2. However, JNKs appeared to play a role, suggesting differential cell type and toxin selectivity of tolerogenic stress responses. Understanding their function or failure will be important to comprehend anti bacterial immune responses. PMID- 26284070 TI - Computational Biology: Modeling Chronic Renal Allograft Injury. AB - New approaches are needed to develop more effective interventions to prevent long term rejection of organ allografts. Computational biology provides a powerful tool to assess the large amount of complex data that is generated in longitudinal studies in this area. This manuscript outlines how our two groups are using mathematical modeling to analyze predictors of graft loss using both clinical and experimental data and how we plan to expand this approach to investigate specific mechanisms of chronic renal allograft injury. PMID- 26284069 TI - T Cell Migration in Rheumatoid Arthritis. AB - Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in joints, associated with synovial hyperplasia and with bone and cartilage destruction. Although the primacy of T cell-related events early in the disease continues to be debated, there is strong evidence that autoantigen recognition by specific T cells is crucial to the pathophysiology of rheumatoid synovitis. In addition, T cells are key components of the immune cell infiltrate detected in the joints of RA patients. Initial analysis of the cytokines released into the synovial membrane showed an imbalance, with a predominance of proinflammatory mediators, indicating a deleterious effect of Th1 T cells. There is nonetheless evidence that Th17 cells also play an important role in RA. T cells migrate from the bloodstream to the synovial tissue via their interactions with the endothelial cells that line synovial postcapillary venules. At this stage, selectins, integrins, and chemokines have a central role in blood cell invasion of synovial tissue, and therefore in the intensity of the inflammatory response. In this review, we will focus on the mechanisms involved in T cell attraction to the joint, the proteins involved in their extravasation from blood vessels, and the signaling pathways activated. Knowledge of these processes will lead to a better understanding of the mechanism by which the systemic immune response causes local joint disorders and will help to provide a molecular basis for therapeutic strategies. PMID- 26284073 TI - Editorial: The Schistosomiasis Vaccine - It is Time to Stand up. PMID- 26284072 TI - Regulation of Lipid Specific and Vitamin Specific Non-MHC Restricted T Cells by Antigen Presenting Cells and Their Therapeutic Potentials. AB - Since initial reports, more than 25 years ago, that T cells recognize lipids in the context on non-polymorphic CD1 molecules, our understanding of antigen presentation to non-peptide-specific T cell populations has deepened. It is now clear that alphabeta T cells bearing semi-invariant T cell receptor, as well as subsets of gammadelta T cells, recognize a variety of self and non-self lipids and contribute to shaping immune responses via cross talk with dendritic cells and B cells. Furthermore, it has been demonstrated that small molecules derived from the microbial riboflavin biosynthetic pathway (vitamin B2) bind monomorphic MR1 molecules and activate mucosal-associated invariant T cells, another population of semi-invariant T cells. Novel insights in the biological relevance of non-peptide-specific T cells have emerged with the development of tetrameric CD1 and MR1 molecules, which has allowed accurate enumeration and functional analysis of CD1- and MR1-restricted T cells in humans and discovery of novel populations of semi-invariant T cells. The phenotype and function of non-peptide specific T cells will be discussed in the context of the known distribution of CD1 and MR1 molecules by different subsets of antigen-presenting cells at steady state and following infection. Concurrent modulation of CD1 transcription and lipid biosynthetic pathways upon TLR stimulation, coupled with efficient lipid antigen processing, result in the increased cell surface expression of antigenic CD1-lipid complexes. Similarly, MR1 expression is almost undetectable in resting APC and it is upregulated following bacterial infection, likely due to stabilization of MR1 molecules by microbial antigens. The tight regulation of CD1 and MR1 expression at steady state and during infection may represent an important mechanism to limit autoreactivity, while promoting T cell responses to foreign antigens. PMID- 26284071 TI - DPP4 in Diabetes. AB - Dipeptidyl-peptidase 4 (DPP4) is a glycoprotein of 110 kDa, which is ubiquitously expressed on the surface of a variety of cells. This exopeptidase selectively cleaves N-terminal dipeptides from a variety of substrates, including cytokines, growth factors, neuropeptides, and the incretin hormones. Expression of DPP4 is substantially dysregulated in a variety of disease states including inflammation, cancer, obesity, and diabetes. Since the incretin hormones, glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide (GIP), are major regulators of post-prandial insulin secretion, inhibition of DPP4 by the gliptin family of drugs has gained considerable interest for the therapy of type 2 diabetic patients. In this review, we summarize the current knowledge on the DPP4-incretin axis and evaluate most recent findings on DPP4 inhibitors. Furthermore, DPP4 as a type II transmembrane protein is also known to be cleaved from the cell membrane involving different metalloproteases in a cell-type-specific manner. Circulating, soluble DPP4 has been identified as a new adipokine, which exerts both para- and endocrine effects. Recently, a novel receptor for soluble DPP4 has been identified, and data are accumulating that the adipokine-related effects of DPP4 may play an important role in the pathogenesis of cardiovascular disease. Importantly, circulating DPP4 is augmented in obese and type 2 diabetic subjects, and it may represent a molecular link between obesity and vascular dysfunction. A critical evaluation of the impact of circulating DPP4 is presented, and the potential role of DPP4 inhibition at this level is also discussed. PMID- 26284075 TI - The Choice of Laboratory Methodology Influences Autoantibody Test Results. AB - During the last 25 years, clinical autoantibody determinations have changed dramatically. Old and slow techniques with high diagnostic specificity have been replaced with automated and faster techniques that most often have a higher diagnostic sensitivity at the expense of a lower diagnostic specificity. Newer techniques are mostly quantitative, allowing for follow-up of autoantibody levels. Whereas the older procedures utilized autoantigens in soluble and native states, most modern techniques rely on autoantigens attached to surfaces, with the risk of exposure of denatured epitopes. Comparisons between antibody measurement techniques can be obtained from the results of external quality assessment programs. As the main objective for external quality assessment is the monitoring of clinical laboratories, they cannot focus on the kind of low-level and often polyreactive sera, which are common in the real world and in which a single definite target response cannot be easily defined. Such common sera are very useful, however, for analysis of differences between autoantibody measurement techniques. The European Consensus Finding Study Group on Autoantibodies has been working with this approach for 28 years. PMID- 26284074 TI - The Role of PKC-theta in CD4+ T Cells and HIV Infection: To the Nucleus and Back Again. AB - Protein kinase C (PKC)-theta is the only member of the PKC family that has the ability to translocate to the immunological synapse between T cells and antigen presenting cells upon T cell receptor and MHC-II recognition. PKC-theta interacts functionally and physically with other downstream effector molecules to mediate T cell activation, differentiation, and migration. It plays a critical role in the generation of Th2 and Th17 responses and is less important in Th1 and CTL responses. PKC-theta has been recently shown to play a role in the nucleus, where it mediates inducible gene expression in the development of memory CD4+ T cells. This novel PKC (nPKC) can up-regulate HIV-1 transcription and PKC-theta activators such as Prostratin have been used in early HIV-1 reservoir eradication studies. The exact manner of the activation of virus by these compounds and the role of PKC-theta, particularly its nuclear form and its association with NF kappaB in both the cytoplasmic and nuclear compartments, needs further precise elucidation especially given the very important role of NF-kappaB in regulating transcription from the integrated retrovirus. Continued studies of this nPKC isoform will give further insight into the complexity of T cell signaling kinases. PMID- 26284076 TI - Contribution of Basophils to Cutaneous Immune Reactions and Th2-Mediated Allergic Responses. AB - Basophils are potent effector cells of innate immunity and also play a role in T helper 2 (Th2)-mediated allergic responses. But, although their in vitro functions are well studied, their in vivo functions remain largely unknown. However, several mouse models of basophil depletion have recently been developed and used to investigate basophil functions. For example, in a croton oil-induced model of irritant contact dermatitis in conditionally basophil-depleted transgenic mice, we found that basophils rapidly infiltrate inflamed skin and subsequently induce infiltration of eosinophils. We also showed that basophils induce Th2 skewing upon epicutaneous sensitization with various haptens and peptide antigens. Intriguingly, basophils also promoted Th2 polarization upon protein antigen exposure in the presence of dendritic cells (DCs). The dermal DC subset associated with Th2 skewing was recently identified as CD301b(+) DC. Such studies with basophil-deficient mouse models have significantly improved our understanding of the mechanisms involved in human immune-related diseases. In this review, we will focus on the relative contribution of basophils and DCs to Th2-mediated allergic responses. PMID- 26284077 TI - Regulatory T-Cell Development in the Human Thymus. AB - The thymus generates a lineage-committed subset of regulatory T-cells (Tregs), best identified by the expression of the transcription factor FOXP3. The development of thymus-derived Tregs is known to require high-avidity interaction with MHC-self peptides leading to the generation of self-reactive Tregs fundamental for the maintenance of self-tolerance. Notwithstanding their crucial role in the control of immune responses, human thymic Treg differentiation remains poorly understood. In this mini-review, we will focus on the developmental stages at which Treg lineage commitment occurs, and their spatial localization in the human thymus, reviewing the molecular requirements, including T-cell receptor and cytokine signaling, as well as the cellular interactions involved. An overview of the impact of described thymic defects on the Treg compartment will be provided, illustrating the importance of these in vivo models to investigate human Treg development. PMID- 26284078 TI - Mutual Interaction of Basophils and T Cells in Chronic Inflammatory Diseases. AB - Basophils are, together with mast cells, typical innate effector cells of allergen-induced IgE-dependent allergic diseases. Both cell types express the high-affinity receptor for IgE (FcepsilonR1), release histamine, inflammatory mediators, and cytokines following FcepsilonR1 cross-linking. Basophils are rare granulocytes in blood, lymphoid, and non-lymphoid tissues, and the difficulties to detect and isolate these cells has hampered the study of their biology and the understanding of their possible role in pathology. Furthermore, the existence of other FcepsilonR1-expressing cells, including professional Ag-presenting dendritic cells, generated some controversy regarding the ability of basophils to express MHC Class II molecules, present Ag and drive naive T cell differentiation into Th2 cells. The focus of this review is to present the recent advances on the interactions between basophils and peripheral blood and tissue memory Th1, Th2, and Th17 cells, as well as their potential role in IgE-independent non-allergic chronic inflammatory disorders, including human inflammatory bowel diseases. Basophils interactions with the innate players of IgE-dependent allergic inflammation, particularly innate lymphoid cells, will also be considered. The previously unrecognized function for basophils in skewing adaptive immune responses opens novel perspectives for the understanding of their contribution to the pathogenesis of inflammatory diseases. PMID- 26284079 TI - Physiological implications of arginine metabolism in plants. AB - Nitrogen is a limiting resource for plant growth in most terrestrial habitats since large amounts of nitrogen are needed to synthesize nucleic acids and proteins. Among the 21 proteinogenic amino acids, arginine has the highest nitrogen to carbon ratio, which makes it especially suitable as a storage form of organic nitrogen. Synthesis in chloroplasts via ornithine is apparently the only operational pathway to provide arginine in plants, and the rate of arginine synthesis is tightly regulated by various feedback mechanisms in accordance with the overall nutritional status. While several steps of arginine biosynthesis still remain poorly characterized in plants, much wider attention has been paid to inter- and intracellular arginine transport as well as arginine-derived metabolites. A role of arginine as alternative source besides glutamate for proline biosynthesis is still discussed controversially and may be prevented by differential subcellular localization of enzymes. Apparently, arginine is a precursor for nitric oxide (NO), although the molecular mechanism of NO production from arginine remains unclear in higher plants. In contrast, conversion of arginine to polyamines is well documented, and in several plant species also ornithine can serve as a precursor for polyamines. Both NO and polyamines play crucial roles in regulating developmental processes as well as responses to biotic and abiotic stress. It is thus conceivable that arginine catabolism serves on the one hand to mobilize nitrogen storages, while on the other hand it may be used to fine-tune development and defense mechanisms against stress. This review summarizes the recent advances in our knowledge about arginine metabolism, with a special focus on the model plant Arabidopsis thaliana, and pinpoints still unresolved critical questions. PMID- 26284080 TI - Proteomics, metabolomics, and ionomics perspectives of salinity tolerance in halophytes. AB - Halophytes are plants which naturally survive in saline environment. They account for ~1% of the total flora of the world. They include both dicots and monocots and are distributed mainly in arid, semi-arid inlands and saline wet lands along the tropical and sub-tropical coasts. Salinity tolerance in halophytes depends on a set of ecological and physiological characteristics that allow them to grow and flourish in high saline conditions. The ability of halophytes to tolerate high salt is determined by the effective coordination between various physiological processes, metabolic pathways and protein or gene networks responsible for delivering salinity tolerance. The salinity responsive proteins belong to diverse functional classes such as photosynthesis, redox homeostasis; stress/defense, carbohydrate and energy metabolism, protein metabolism, signal transduction and membrane transport. The important metabolites which are involved in salt tolerance of halophytes are proline and proline analog (4-hydroxy-N-methyl proline), glycine betaine, pinitol, myo-inositol, mannitol, sorbitol, O methylmucoinositol, and polyamines. In halophytes, the synthesis of specific proteins and osmotically active metabolites control ion and water flux and support scavenging of oxygen radicals under salt stress condition. The present review summarizes the salt tolerance mechanisms of halophytes by elucidating the recent studies that have focused on proteomic, metabolomic, and ionomic aspects of various halophytes in response to salinity. By integrating the information from halophytes and its comparison with glycophytes could give an overview of salt tolerance mechanisms in halophytes, thus laying down the pavement for development of salt tolerant crop plants through genetic modification and effective breeding strategies. PMID- 26284081 TI - The plastoquinone pool, poised for cyclic electron flow? PMID- 26284082 TI - QueTAL: a suite of tools to classify and compare TAL effectors functionally and phylogenetically. AB - Transcription Activator-Like (TAL) effectors from Xanthomonas plant pathogenic bacteria can bind to the promoter region of plant genes and induce their expression. DNA-binding specificity is governed by a central domain made of nearly identical repeats, each determining the recognition of one base pair via two amino acid residues (a.k.a. Repeat Variable Di-residue, or RVD). Knowing how TAL effectors differ from each other within and between strains would be useful to infer functional and evolutionary relationships, but their repetitive nature precludes reliable use of traditional alignment methods. The suite QueTAL was therefore developed to offer tailored tools for comparison of TAL effector genes. The program DisTAL considers each repeat as a unit, transforms a TAL effector sequence into a sequence of coded repeats and makes pair-wise alignments between these coded sequences to construct trees. The program FuncTAL is aimed at finding TAL effectors with similar DNA-binding capabilities. It calculates correlations between position weight matrices of potential target DNA sequence predicted from the RVD sequence, and builds trees based on these correlations. The programs accurately represented phylogenetic and functional relationships between TAL effectors using either simulated or literature-curated data. When using the programs on a large set of TAL effector sequences, the DisTAL tree largely reflected the expected species phylogeny. In contrast, FuncTAL showed that TAL effectors with similar binding capabilities can be found between phylogenetically distant taxa. This suite will help users to rapidly analyse any TAL effector genes of interest and compare them to other available TAL genes and should improve our understanding of TAL effectors evolution. It is available at http://bioinfo-web.mpl.ird.fr/cgi-bin2/quetal/quetal.cgi. PMID- 26284083 TI - How tree roots respond to drought. AB - The ongoing climate change is characterized by increased temperatures and altered precipitation patterns. In addition, there has been an increase in both the frequency and intensity of extreme climatic events such as drought. Episodes of drought induce a series of interconnected effects, all of which have the potential to alter the carbon balance of forest ecosystems profoundly at different scales of plant organization and ecosystem functioning. During recent years, considerable progress has been made in the understanding of how aboveground parts of trees respond to drought and how these responses affect carbon assimilation. In contrast, processes of belowground parts are relatively underrepresented in research on climate change. In this review, we describe current knowledge about responses of tree roots to drought. Tree roots are capable of responding to drought through a variety of strategies that enable them to avoid and tolerate stress. Responses include root biomass adjustments, anatomical alterations, and physiological acclimations. The molecular mechanisms underlying these responses are characterized to some extent, and involve stress signaling and the induction of numerous genes, leading to the activation of tolerance pathways. In addition, mycorrhizas seem to play important protective roles. The current knowledge compiled in this review supports the view that tree roots are well equipped to withstand drought situations and maintain morphological and physiological functions as long as possible. Further, the reviewed literature demonstrates the important role of tree roots in the functioning of forest ecosystems and highlights the need for more research in this emerging field. PMID- 26284084 TI - Proteomic analysis and candidate allergenic proteins in Populus deltoides CL. "2KEN8" mature pollen. AB - Proteomic analysis was used to generate a map of Populus deltoides CL. "2KEN8" mature pollen proteins. By applying 2-D electrophoresis, we resolved 403 protein spots from mature pollen. Using the matrix-assisted laser desorption/ionization time time-of-flight/time-of-flight tandem mass spectrometry method, we identified 178 distinct proteins from 218 protein spots expressed in mature pollen. Moreover, out of these, 28 proteins were identified as putative allergens. The expression patterns of these putative allergen genes indicate that several of these genes are highly expressed in pollen. In addition, the members of profilin allergen family were analyzed and their expression patterns were compared with their homologous genes in Arabidopsis and rice. Knowledge of these identified allergens has the potential to improve specific diagnosis and allergen immunotherapy treatment for patients with poplar pollen allergy. PMID- 26284085 TI - Pushing the boundaries of resistance: insights from Brachypodium-rust interactions. AB - The implications of global population growth urge transformation of current food and bioenergy production systems to sustainability. Members of the family Poaceae are of particular importance both in food security and for their applications as biofuel substrates. For centuries, rust fungi have threatened the production of valuable crops such as wheat, barley, oat, and other small grains; similarly, biofuel crops can also be susceptible to these pathogens. Emerging rust pathogenic races with increased virulence and recurrent rust epidemics around the world point out the vulnerability of monocultures. Basic research in plant immunity, especially in model plants, can make contributions to understanding plant resistance mechanisms and improve disease management strategies. The development of the grass Brachypodium distachyon as a genetically tractable model for monocots, especially temperate cereals and grasses, offers the possibility to overcome the experimental challenges presented by the genetic and genomic complexities of economically valuable crop plants. The numerous resources and tools available in Brachypodium have opened new doors to investigate the underlying molecular and genetic bases of plant-microbe interactions in grasses and evidence demonstrating the applicability and advantages of working with B. distachyon is increasing. Importantly, several interactions between B. distachyon and devastating plant pathogens, such rust fungi, have been examined in the context of non-host resistance. Here, we discuss the use of B. distachyon in these various pathosystems. Exploiting B. distachyon to understand the mechanisms underpinning disease resistance to non-adapted rust fungi may provide effective and durable approaches to fend off these pathogens. The close phylogenetic relationship among Brachypodium spp. and grasses with industrial and agronomic value support harnessing this model plant to improve cropping systems and encourage its use in translational research. PMID- 26284086 TI - Functional analysis of the BRI1 receptor kinase by Thr-for-Ser substitution in a regulatory autophosphorylation site. AB - BRI1 becomes highly phosphorylated in vivo upon perception of the ligand, brassinolide, as a result of autophosphorylation and transphosphorylation by its co-receptor kinase, BAK1. Important autophosphorylation sites include those involved in activation of kinase activity and those that are inhibitory, such as Ser-891. The inhibitory sites are autophosphorylated after kinase activation has been achieved and are postulated to contribute to deactivation of the kinase. The function of phosphosites is usually tested by substituting a non-phosphorylatable residue or an acidic residue that can act as a phosphomimetic. What has typically not been examined is substitution of a Thr for a Ser phosphosite (or vice versa) but given that Thr and Ser are not equivalent amino acids this type of substitution may represent a new approach to engineer regulatory phosphorylation. In the present study with BRI1, we substituted Thr at the Ser-891 phosphosite to generate the S891T directed mutant. The recombinant Flag-BRI1 (S891T) cytoplasmic domain protein (the S891T protein) was catalytically active and phosphorylation occurred at the engineered Thr-891 site. However, the S891T recombinant protein autophosphorylated more slowly than the wild-type protein during expression in E. coli. As a result, activation of peptide kinase activity (measured in vitro) was delayed as was transphosphorylation of bacterial proteins in situ. Stable transgenic expression of BRI1 (S891T)-Flag in Arabidopsis bri1-5 plants did not fully rescue the brassinosteroid (BR) phenotype indicating that BR signaling was constrained. Our working model is that restricted signaling in the S891T plants occurs as a result of the reduced rate of activation of the mutant BRI1 kinase by autophosphorylation. These results provide the platform for future studies to critically test this new model in vivo and establish Ser-Thr substitutions at phosphosites as an interesting approach to consider with other protein kinases. PMID- 26284087 TI - Functional properties and structural characterization of rice delta(1)-pyrroline 5-carboxylate reductase. AB - The majority of plant species accumulate high intracellular levels of proline to cope with hyperosmotic stress conditions. Proline synthesis from glutamate is tightly regulated at both the transcriptional and the translational levels, yet little is known about the mechanisms for post-translational regulation of the enzymatic activities involved. The gene coding in rice (Oryza sativa L.) for delta(1)-pyrroline-5-carboxylate (P5C) reductase, the enzyme that catalyzes the second and final step in this pathway, was isolated and expressed in Escherichia coli. The structural and functional properties of the affinity-purified protein were characterized. As for most species, rice P5C reductase was able to use in vitro either NADH or NADPH as the electron donor. However, strikingly different effects of cations and anions were found depending on the pyridine nucleotide used, namely inhibition of NADH-dependent activity and stimulation of NADPH dependent activity. Moreover, physiological concentrations of proline and NADP(+) were strongly inhibitory for the NADH-dependent reaction, whereas the NADPH dependent activity was mildly affected. Our results suggest that only NADPH may be used in vivo and that stress-dependent variations in ion homeostasis and NADPH/NADP(+) ratio could modulate enzyme activity, being functional in promoting proline accumulation and potentially also adjusting NADPH consumption during the defense against hyperosmotic stress. The apparent molecular weight of the native protein observed in size exclusion chromatography indicated a high oligomerization state. We also report the first crystal structure of a plant P5C reductase at 3.40-A resolution, showing a decameric quaternary assembly. Based on the structure, it was possible to identify dynamic structural differences among rice, human, and bacterial enzymes. PMID- 26284088 TI - Is the efficacy of biological control against plant diseases likely to be more durable than that of chemical pesticides? AB - The durability of a control method for plant protection is defined as the persistence of its efficacy in space and time. It depends on (i) the selection pressure exerted by it on populations of plant pathogens and (ii) on the capacity of these pathogens to adapt to the control method. Erosion of effectiveness of conventional plant protection methods has been widely studied in the past. For example, apparition of resistance to chemical pesticides in plant pathogens or pests has been extensively documented. The durability of biological control has often been assumed to be higher than that of chemical control. Results concerning pest management in agricultural systems have shown that this assumption may not always be justified. Resistance of various pests to one or several toxins of Bacillus thuringiensis and apparition of resistance of the codling moth Cydia pomonella to the C. pomonella granulovirus have, for example, been described. In contrast with the situation for pests, the durability of biological control of plant diseases has hardly been studied and no scientific reports proving the loss of efficiency of biological control agents against plant pathogens in practice has been published so far. Knowledge concerning the possible erosion of effectiveness of biological control is essential to ensure a durable efficacy of biological control agents on target plant pathogens. This knowledge will result in identifying risk factors that can foster the selection of strains of plant pathogens resistant to biological control agents. It will also result in identifying types of biological control agents with lower risk of efficacy loss, i.e., modes of action of biological control agents that does not favor the selection of resistant isolates in natural populations of plant pathogens. An analysis of the scientific literature was then conducted to assess the potential for plant pathogens to become resistant to biological control agents. PMID- 26284090 TI - P5CDH affects the pathways contributing to Pro synthesis after ProDH activation by biotic and abiotic stress conditions. AB - Plants facing adverse conditions usually alter proline (Pro) metabolism, generating changes that help restore the cellular homeostasis. These organisms synthesize Pro from glutamate (Glu) or ornithine (Orn) by two-step reactions that share Delta(1) pyrroline-5-carboxylate (P5C) as intermediate. In the catabolic process, Pro is converted back to Glu using a different pathway that involves Pro dehydrogenase (ProDH), P5C dehydrogenase (P5CDH), and P5C as intermediate. Little is known about the coordination of the catabolic and biosynthetic routes under stress. To address this issue, we analyzed how P5CDH affects the activation of Pro synthesis, in Arabidopsis tissues that increase ProDH activity by transient exposure to exogenous Pro, or infection with Pseudomonas syringae pv. tomato. Wild-type (Col-0) and p5cdh mutant plants subjected to these treatments were used to monitor the Pro, Glu, and Orn levels, as well as the expression of genes from Pro metabolism. Col-0 and p5cdh tissues consecutively activated ProDH and Pro biosynthetic genes under both conditions. However, they manifested a different coordination between these routes. When external Pro supply was interrupted, wild type leaves degraded Pro to basal levels at which point Pro synthesis, mainly via Glu, became activated. Under the same condition, p5cdh leaves sustained ProDH induction without reducing the Pro content but rather increasing it, apparently by stimulating the Orn pathway. In response to pathogen infection, both genotypes showed similar trends. While Col-0 plants seemed to induce both Pro biosynthetic routes, p5cdh mutant plants may primarily activate the Orn route. Our study contributes to the functional characterization of P5CDH in biotic and abiotic stress conditions, by revealing its capacity to modulate the fate of P5C, and prevalence of Orn or Glu as Pro precursors in tissues that initially consumed Pro. PMID- 26284089 TI - Evolution of plant delta(1)-pyrroline-5-carboxylate reductases from phylogenetic and structural perspectives. AB - Proline plays a crucial role in cell growth and stress responses, and its accumulation is essential for the tolerance of adverse environmental conditions in plants. Two routes are used to biosynthesize proline in plants. The main route uses glutamate as a precursor, while in the other route proline is derived from ornithine. The terminal step of both pathways, the conversion of delta(1) pyrroline-5-carboxylate (P5C) to L-proline, is catalyzed by P5C reductase (P5CR) using NADH or NADPH as a cofactor. Since P5CRs are important housekeeping enzymes, they are conserved across all domains of life and appear to be relatively unaffected throughout evolution. However, global analysis of these enzymes unveiled significant functional diversity in the preference for cofactors (NADPH vs. NADH), variation in metal dependence and the differences in the oligomeric state. In our study we investigated evolutionary patterns through phylogenetic and structural analysis of P5CR representatives from all kingdoms of life, with emphasis on the plant species. We also attempted to correlate local sequence/structure variation among the functionally and structurally characterized members of the family. PMID- 26284091 TI - Identification of a core set of rhizobial infection genes using data from single cell-types. AB - Genome-wide expression studies on nodulation have varied in their scale from entire root systems to dissected nodules or root sections containing nodule primordia (NP). More recently efforts have focused on developing methods for isolation of root hairs from infected plants and the application of laser-capture microdissection technology to nodules. Here we analyze two published data sets to identify a core set of infection genes that are expressed in the nodule and in root hairs during infection. Among the genes identified were those encoding phenylpropanoid biosynthesis enzymes including Chalcone-O-Methyltransferase which is required for the production of the potent Nod gene inducer 4',4-dihydroxy-2 methoxychalcone. A promoter-GUS analysis in transgenic hairy roots for two genes encoding Chalcone-O-Methyltransferase isoforms revealed their expression in rhizobially infected root hairs and the nodule infection zone but not in the nitrogen fixation zone. We also describe a group of Rhizobially Induced Peroxidases whose expression overlaps with the production of superoxide in rhizobially infected root hairs and in nodules and roots. Finally, we identify a cohort of co-regulated transcription factors as candidate regulators of these processes. PMID- 26284092 TI - Identification and expression profiling analysis of calmodulin-binding transcription activator genes in maize (Zea mays L.) under abiotic and biotic stresses. AB - The calmodulin-binding transcription activators (CAMTA) play critical roles in plant growth and responses to environmental stimuli. However, how CAMTAs function in responses to abiotic and biotic stresses in maize (Zea mays L.) is largely unknown. In this study, we first identified all the CAMTA homologous genes in the whole genome of maize. The results showed that nine ZmCAMTA genes showed highly diversified gene structures and tissue-specific expression patterns. Many ZmCAMTA genes displayed high expression levels in the roots. We then surveyed the distribution of stress-related cis-regulatory elements in the -1.5 kb promoter regions of ZmCAMTA genes. Notably, a large number of stress-related elements present in the promoter regions of some ZmCAMTA genes, indicating a genetic basis of stress expression regulation of these genes. Quantitative real-time PCR was used to test the expression of ZmCAMTA genes under several abiotic stresses (drought, salt, and cold), various stress-related hormones [abscisic acid, auxin, salicylic acid (SA), and jasmonic acid] and biotic stress [rice black-streaked dwarf virus (RBSDV) infection]. Furthermore, the expression pattern of ZmCAMTA genes under RBSDV infection was analyzed to investigate their potential roles in responses of different maize cultivated varieties to RBSDV. The expression of most ZmCAMTA genes responded to both abiotic and biotic stresses. The data will help us to understand the roles of CAMTA-mediated Ca(2+) signaling in maize tolerance to environmental stresses. PMID- 26284093 TI - The Phaseolus vulgaris PvTRX1h gene regulates plant hormone biosynthesis in embryogenic callus from common bean. AB - Common bean is the most important grain legume in the human diet. Bean improvement efforts have been focused on classical breeding techniques because bean is recalcitrant to both somatic embryogenesis and in vitro regeneration. This study was undertaken to better understand the process of somatic embryogenesis in the common bean. We focused on the mechanisms by which somatic embryogenesis in plants is regulated and the interaction of these mechanisms with plant hormones. Specifically, we examined the role of the gene PvTRX1h, an ortholog of a major known histone lysine methyltransferase in plants, in somatic embryo generation. Given the problems with regeneration and transformation, we chose to develop and use regeneration-competent callus that could be successively transformed. Embryogenic calli of common bean were generated and transformed with the PvTRX1hRiA construction to down-regulate, by RNA interference, expression of the PvTRX1h gene. Plant hormone content was measured by mass spectrometry and gene expression was assessed by q-PCR. Detailed histological analysis was performed on selected transgenic embryogenic calli. It was determined that down regulation of PvTRX1h gene was accompanied by altered concentrations of plant hormones in the calli. PvTRX1h regulated the expression of genes involved in auxin biosynthesis and embryogenic calli in which PvTRX1h was down-regulated were capable of differentiation into somatic embryos. Also, down-regulation of PvTRX1h showed increased transcript abundance of a gene coding for a second histone lysine methyltransferase, PvASHH2h. Accordingly, the PvTRX1h gene is involved in the synthesis of plant hormones in common bean callus. These results shed light on the crosstalk among histone methyltransferases and plant hormone signaling and on gene regulation during somatic embryo generation. PMID- 26284094 TI - Glutamine synthetase in Medicago truncatula, unveiling new secrets of a very old enzyme. AB - Glutamine synthetase (GS) catalyzes the first step at which nitrogen is brought into cellular metabolism and is also involved in the reassimilation of ammonium released by a number of metabolic pathways. Due to its unique position in plant nitrogen metabolism, GS plays essential roles in all aspects of plant development, from germination to senescence, and is a key component of nitrogen use efficiency (NUE) and plant yield. Understanding the mechanisms regulating GS activity is therefore of utmost importance and a great effort has been dedicated to understand how GS is regulated in different plant species. The present review summarizes exciting recent developments concerning the structure and regulation of GS isoenzymes, using the model legume Medicago truncatula. These include the understanding of the structural determinants of both the cytosolic and plastid located isoenzymes, the existence of a seed-specific GS gene unique to M. truncatula and closely related species and the discovery that GS isoenzymes are regulated by nitric oxide at the post-translational level. The data is discussed and integrated with the potential roles of the distinct GS isoenzymes within the whole plant context. PMID- 26284095 TI - Candidate effector proteins of the necrotrophic apple canker pathogen Valsa mali can suppress BAX-induced PCD. AB - Canker caused by the Ascomycete Valsa mali is the most destructive disease of apple in Eastern Asia, resulting in yield losses of up to 100%. This necrotrophic fungus induces severe necrosis on apple, eventually leading to the death of the whole tree. Identification of necrosis inducing factors may help to unravel the molecular bases for colonization of apple trees by V. mali. As a first step toward this goal, we identified and characterized the V. mali repertoire of candidate effector proteins (CEPs). In total, 193 secreted proteins with no known function were predicted from genomic data, of which 101 were V. mali-specific. Compared to non-CEPs predicted for the V. mali secretome, CEPs have shorter sequence length and a higher content of cysteine residues. Based on transient over-expression in Nicotiana benthamiana performed for 70 randomly selected CEPs, seven V. mali Effector Proteins (VmEPs) were shown to significantly suppress BAX induced PCD. Furthermore, targeted deletion of VmEP1 resulted in a significant reduction of virulence. These results suggest that V. mali expresses secreted proteins that can suppress PCD usually associated with effector-triggered immunity (ETI). ETI in turn may play an important role in the V. mali-apple interaction. The ability of V. mali to suppress plant ETI sheds a new light onto the interaction of a necrotrophic fungus with its host plant. PMID- 26284096 TI - Radioactivity and the environment: technical approaches to understand the role of arbuscular mycorrhizal plants in radionuclide bioaccumulation. AB - Phytoaccumulation of radionuclides is of significant interest with regards to monitoring radionuclide build-up in food chains, developing methods for environmental bioremediation and for ecological management. There are many gaps in our understanding of the characteristics and mechanisms of plant radionuclide accumulation, including the importance of symbiotically-associated arbuscular mycorrhizal (AM) fungi. We first briefly review the evidence that demonstrates the ability of AM fungi to enhance the translocation of (238)U into plant root tissues, and how fungal association may prevent further mobilization into shoot tissues. We then focus on approaches that should further advance our knowledge of AM fungi-plant radionuclide accumulation. Current research has mostly used artificial cultivation methods and we consider how more ecologically-relevant analysis might be performed. The use of synchrotron-based X-ray fluorescence imaging and absorption spectroscopy techniques to understand the mechanisms of radionuclide transfer from soil to plant via AM fungi is evaluated. Without such further knowledge, the behavior and mobilization of radionuclides cannot be accurately modeled and the potential risks cannot be accurately predicted. PMID- 26284097 TI - Co-expression of xerophyte Zygophyllum xanthoxylum ZxNHX and ZxVP1-1 confers enhanced salinity tolerance in chimeric sugar beet (Beta vulgaris L.). AB - Salinity is one of the major abiotic stresses that limit the growth and productivity of sugar beet (Beta vulgaris L.). To improve sugar beet's salinity tolerance, the ZxNHX and ZxVP1-1 genes encoding tonoplast Na(+)/H(+) antiporter and H(+)-PPase from xerophyte Zygophyllum xanthoxylum were co-expressed by Agrobacterium tumefaciens-mediated transformation. It is showed here that co expression of ZxNHX and ZxVP1-1 confers enhanced salinity tolerance to the transformed sugar beet plants compared with the wild-type (WT) plants. The chimeric plants grew well in the presence of high salinity (400 mM NaCl), whereas WT plants displayed chlorosis and died within 8 days. Compared to WT plants, the chimeric plants co-expressing ZxNHX and ZxVP1-1 accumulated more proline, Na(+) and K(+) in their leaves and petioles when exposed to high salinity, which caused lower solute potential, retained more water and thus subjected to lesser cell membrane damage. Interestingly, the chimeric plants accumulated higher sucrose, glucose and fructose contents in their storage roots than WT plants in the absence or presence of high salinity. Our results suggested that co-expression of ZxNHX and ZxVP1-1 improved the osmoregulatory capacity in chimeric sugar beet through increased compartmentalization of ions into the vacuoles by enhancing the activity of proton pumps and thus mitigated Na(+)-toxicity for plants. PMID- 26284098 TI - Binary stress induces an increase in indole alkaloid biosynthesis in Catharanthus roseus. AB - Catharanthus roseus is an important medicinal plant, which produces a variety of indole alkaloids of significant pharmaceutical relevance. In the present study, we aimed to investigate the potential stress-induced increase of indole alkaloid biosynthesis in C. roseus using proteomic technique. The contents of the detectable alkaloids ajmalicine, vindoline, catharanthine, and strictosidine in C. roseus were significantly increased under binary stress. Proteomic analysis revealed that the abundance of proteins related to tricarboxylic acid cycle and cell wall was largely increased; while, that of proteins related to tetrapyrrole synthesis and photosynthesis was decreased. Of note, 10-hydroxygeraniol oxidoreductase, which is involved in the biosynthesis of indole alkaloid was two fold more abundant in treated group compared to the control. In addition, mRNA expression levels of genes involved in the indole alkaloid biosynthetic pathway indicated an up-regulation in their transcription in C. roseus under UV-B irradiation. These results suggest that binary stress might negatively affect the process of photosynthesis in C. roseus. In addition, the induction of alkaloid biosynthesis appears to be responsive to binary stress. PMID- 26284099 TI - Transcriptome, carbohydrate, and phytohormone analysis of Petunia hybrida reveals a complex disturbance of plant functional integrity under mild chilling stress. AB - Cultivation of chilling-tolerant ornamental crops at lower temperature could reduce the energy demands of heated greenhouses. To provide a better understanding of how sub-optimal temperatures (12 degrees C vs. 16 degrees C) affect growth of the sensitive Petunia hybrida cultivar 'SweetSunshine Williams', the transcriptome, carbohydrate metabolism, and phytohormone homeostasis were monitored in aerial plant parts over 4 weeks by use of a microarray, enzymatic assays and GC-MS/MS. The data revealed three consecutive phases of chilling response. The first days were marked by a strong accumulation of sugars, particularly in source leaves, preferential up-regulation of genes in the same tissue and down-regulation of several genes in the shoot apex, especially those involved in the abiotic stress response. The midterm phase featured a partial normalization of carbohydrate levels and gene expression. After 3 weeks of chilling exposure, a new stabilized balance was established. Reduced hexose levels in the shoot apex, reduced ratios of sugar levels between the apex and source leaves and a higher apical sucrose/hexose ratio, associated with decreased activity and expression of cell wall invertase, indicate that prolonged chilling induced sugar accumulation in source leaves at the expense of reduced sugar transport to and reduced sucrose utilization in the shoot. This was associated with reduced levels of indole-3-acetic acid and abscisic acid in the apex and high numbers of differentially, particularly up-regulated genes, especially in the source leaves, including those regulating histones, ethylene action, transcription factors, and a jasmonate-ZIM-domain protein. Transcripts of one Jumonji C domain containing protein and one expansin accumulated in source leaves throughout the chilling period. The results reveal a dynamic and complex disturbance of plant function in response to mild chilling, opening new perspectives for the comparative analysis of differently tolerant cultivars. PMID- 26284100 TI - The battle in the apoplast: further insights into the roles of proteases and their inhibitors in plant-pathogen interactions. AB - Upon host penetration, fungal pathogens secrete a plethora of effectors to promote disease, including proteases that degrade plant antimicrobial proteins, and protease inhibitors (PIs) that inhibit plant proteases with antimicrobial activity. Conversely, plants secrete proteases and PIs to protect themselves against pathogens or to mediate recognition of pathogen proteases and PIs, which leads to induction of defense responses. Many examples of proteases and PIs mediating effector-triggered immunity in host plants have been reported in the literature, but little is known about their role in compromising basal defense responses induced by microbe-associated molecular patterns. Recently, several reports appeared in literature on secreted fungal proteases that modify or degrade pathogenesis-related proteins, including plant chitinases or PIs that compromise their activities. This prompted us to review the recent advances on proteases and PIs involved in fungal virulence and plant defense. Proteases and PIs from plants and their fungal pathogens play an important role in the arms race between plants and pathogens, which has resulted in co-evolutionary diversification and adaptation shaping pathogen lifestyles. PMID- 26284101 TI - Long-term boron-deficiency-responsive genes revealed by cDNA-AFLP differ between Citrus sinensis roots and leaves. AB - Seedlings of Citrus sinensis (L.) Osbeck were supplied with boron (B)-deficient (without H3BO3) or -sufficient (10 MUM H3BO3) nutrient solution for 15 weeks. We identified 54 (38) and 38 (45) up (down)-regulated cDNA-AFLP bands (transcript derived fragments, TDFs) from B-deficient leaves and roots, respectively. These TDFs were mainly involved in protein and amino acid metabolism, carbohydrate and energy metabolism, nucleic acid metabolism, cell transport, signal transduction, and stress response and defense. The majority of the differentially expressed TDFs were isolated only from B-deficient roots or leaves, only seven TDFs with the same GenBank ID were isolated from the both. In addition, ATP biosynthesis related TDFs were induced in B-deficient roots, but unaffected in B-deficient leaves. Most of the differentially expressed TDFs associated with signal transduction and stress defense were down-regulated in roots, but up-regulated in leaves. TDFs related to protein ubiquitination and proteolysis were induced in B deficient leaves except for one TDF, while only two down-regulated TDFs associated with ubiquitination were detected in B-deficient roots. Thus, many differences existed in long-term B-deficiency-responsive genes between roots and leaves. In conclusion, our findings provided a global picture of the differential responses occurring in B-deficient roots and leaves and revealed new insight into the different adaptive mechanisms of C. sinensis roots and leaves to B-deficiency at the transcriptional level. PMID- 26284103 TI - Responses of symbiotic nitrogen-fixing common bean to aluminum toxicity and delineation of nodule responsive microRNAs. AB - Aluminum (Al) toxicity is widespread in acidic soils where the common bean (Phaseolus vulgaris), the most important legume for human consumption, is produced and it is a limiting factor for crop production and symbiotic nitrogen fixation. We characterized the nodule responses of common bean plants inoculated with Rhizobioum tropici CIAT899 and the root responses of nitrate-fertilized plants exposed to excess Al in low pH, for long or short periods. A 43-50% reduction in nitrogenase activity indicates that Al toxicity (Alt) highly affected nitrogen fixation in common bean. Bean roots and nodules showed characteristic symptoms for Alt. In mature nodules Al accumulation and lipoperoxidation were observed in the infected zone, while callose deposition and cell death occurred mainly in the nodule cortex. Regulatory mechanisms of plant responses to metal toxicity involve microRNAs (miRNAs) along other regulators. Using a miRNA-macroarray hybridization approach we identified 28 (14 up regulated) Alt nodule-responsive miRNAs. We validated (quantitative reverse transcriptase-PCR) the expression of eight nodule responsive miRNAs in roots and in nodules exposed to high Al for long or short periods. The inverse correlation between the target and miRNA expression ratio (stress:control) was observed in every case. Generally, miRNAs showed a higher earlier response in roots than in nodules. Some of the common bean Alt-responsive miRNAs identified has also been reported as differentially expressed in other plant species subjected to similar stress condition. miRNA/target nodes analyzed in this work are known to be involved in relevant signaling pathways, thus we propose that the participation of miR164/NAC1 (NAM/ATAF/CUC transcription factor) and miR393/TIR1 (TRANSPORT INHIBITOR RESPONSE 1-like protein) in auxin and of miR170/SCL (SCARECROW-like protein transcription factor) in gibberellin signaling is relevant for common bean response/adaptation to Al stress. Our data provide a foundation for evaluating the individual roles of miRNAs in the response of common bean nodules to Alt. PMID- 26284104 TI - DNA barcoding of perennial fruit tree species of agronomic interest in the genus Annona (Annonaceae). AB - The DNA barcode initiative aims to establish a universal protocol using short genetic sequences to discriminate among animal and plant species. Although many markers have been proposed to become the barcode of plants, the Consortium for the Barcode of Life (CBOL) Plant Working Group recommended using as a core the combination of two portions of plastid coding region, rbcL and matK. In this paper, specific markers based on matK sequences were developed for 7 closely related Annona species of agronomic interest (Annona cherimola, A. reticulata, A. squamosa, A. muricata, A. macroprophyllata, A. glabra, and A. purpurea) and the discrimination power of both rbcL and matK was tested using also sequences of the genus Annona available in the Barcode of Life Database (BOLD) data systems. The specific sequences developed allowed the discrimination among all those species tested. Moreover, the primers generated were validated in six additional species of the genus (A. liebmanniana, A. longiflora, A. montana, A. senegalensis, A. emarginata and A. neosalicifolia) and in an interspecific hybrid (A. cherimola x A. squamosa). The development of a fast, reliable and economic approach for species identification in these underutilized subtropical fruit crops in a very initial state of domestication is of great importance in order to optimize genetic resource management. PMID- 26284105 TI - Quantitative proteomics reveals role of sugar in decreasing photosynthetic activity due to Fe deficiency. PMID- 26284102 TI - Plastid genomics in horticultural species: importance and applications for plant population genetics, evolution, and biotechnology. AB - During the evolution of the eukaryotic cell, plastids, and mitochondria arose from an endosymbiotic process, which determined the presence of three genetic compartments into the incipient plant cell. After that, these three genetic materials from host and symbiont suffered several rearrangements, bringing on a complex interaction between nuclear and organellar gene products. Nowadays, plastids harbor a small genome with ~130 genes in a 100-220 kb sequence in higher plants. Plastid genes are mostly highly conserved between plant species, being useful for phylogenetic analysis in higher taxa. However, intergenic spacers have a relatively higher mutation rate and are important markers to phylogeographical and plant population genetics analyses. The predominant uniparental inheritance of plastids is like a highly desirable feature for phylogeny studies. Moreover, the gene content and genome rearrangements are efficient tools to capture and understand evolutionary events between different plant species. Currently, genetic engineering of the plastid genome (plastome) offers a number of attractive advantages as high-level of foreign protein expression, marker gene excision, gene expression in operon and transgene containment because of maternal inheritance of plastid genome in most crops. Therefore, plastid genome can be used for adding new characteristics related to synthesis of metabolic compounds, biopharmaceutical, and tolerance to biotic and abiotic stresses. Here, we describe the importance and applications of plastid genome as tools for genetic and evolutionary studies, and plastid transformation focusing on increasing the performance of horticultural species in the field. PMID- 26284107 TI - Estimating genetic effect sizes under joint disease-endophenotype models in presence of gene-environment interactions. AB - Effects of genetic variants on the risk of complex diseases estimated from association studies are typically small. Nonetheless, variants may have important effects in presence of specific levels of environmental exposures, and when a trait related to the disease (endophenotype) is either normal or impaired. We propose polytomous and transition models to represent the relationship between disease, endophenotype, genotype and environmental exposure in family studies. Model coefficients were estimated using generalized estimating equations and were used to derive gene-environment interaction effects and genotype effects at specific levels of exposure. In a simulation study, estimates of the effect of a genetic variant were substantially higher when both an endophenotype and an environmental exposure modifying the variant effect were taken into account, particularly under transition models, compared to the alternative of ignoring the endophenotype. Illustration of the proposed modeling with the metabolic syndrome, abdominal obesity, physical activity and polymorphisms in the NOX3 gene in the Quebec Family Study revealed that the positive association of the A allele of rs1375713 with the metabolic syndrome at high levels of physical activity was only detectable in subjects without abdominal obesity, illustrating the importance of taking into account the abdominal obesity endophenotype in this analysis. PMID- 26284106 TI - The Xanthomonas effector XopJ triggers a conditional hypersensitive response upon treatment of N. benthamiana leaves with salicylic acid. AB - XopJ is a Xanthomonas type III effector protein that promotes bacterial virulence on susceptible pepper plants through the inhibition of the host cell proteasome and a resultant suppression of salicylic acid (SA) - dependent defense responses. We show here that Nicotiana benthamiana leaves transiently expressing XopJ display hypersensitive response (HR) -like symptoms when exogenously treated with SA. This apparent avirulence function of XopJ was further dependent on effector myristoylation as well as on an intact catalytic triad, suggesting a requirement of its enzymatic activity for HR-like symptom elicitation. The ability of XopJ to cause a HR-like symptom development upon SA treatment was lost upon silencing of SGT1 and NDR1, respectively, but was independent of EDS1 silencing, suggesting that XopJ is recognized by an R protein of the CC-NBS-LRR class. Furthermore, silencing of NPR1 abolished the elicitation of HR-like symptoms in XopJ expressing leaves after SA application. Measurement of the proteasome activity indicated that proteasome inhibition by XopJ was alleviated in the presence of SA, an effect that was not observed in NPR1 silenced plants. Our results suggest that XopJ - triggered HR-like symptoms are closely related to the virulence function of the effector and that XopJ follows a two-signal model in order to elicit a response in the non-host plant N. benthamiana. PMID- 26284108 TI - Identifying critical differentiation state of MCF-7 cells for breast cancer by dynamical network biomarkers. AB - Identifying the pre-transition state just before a critical transition during a complex biological process is a challenging task, because the state of the system may show neither apparent changes nor clear phenomena before this critical transition during the biological process. By exploring rich correlation information provided by high-throughput data, the dynamical network biomarker (DNB) can identify the pre-transition state. In this work, we apply DNB to detect an early-warning signal of breast cancer on the basis of gene expression data of MCF-7 cell differentiation. We find a number of the related modules and pathways in the samples, which can be used not only as the biomarkers of cancer cells but also as the drug targets. Both functional and pathway enrichment analyses validate the results. PMID- 26284109 TI - Hold your horSSEs: controlling structure-selective endonucleases MUS81 and Yen1/GEN1. AB - Repair of DNA lesions through homologous recombination promotes the establishment of stable chromosomal interactions. Multiple helicases, topoisomerases and structure-selective endonucleases (SSEs) act upon recombining joint molecules (JMs) to disengage chromosomal connections and safeguard chromosome segregation. Recent studies on two conserved SSEs - MUS81 and Yen1/GEN1- uncovered multiple layers of regulation that operate to carefully tailor JM-processing according to specific cellular needs. Temporal restriction of SSE function imposes a hierarchy in pathway usage that ensures efficient JM-processing while minimizing reciprocal exchanges between the recombining DNAs. Whereas a conserved strategy of fine tuning SSE functions exists in different model systems, the precise molecular mechanisms to implement it appear to be significantly different. Here, we summarize the current knowledge on the cellular switches that are in place to control MUS81 and Yen1/GEN1 functions. PMID- 26284110 TI - Corrigendum: Long-term survival in a child with severe encephalopathy, multiple respiratory chain deficiency and GFM1 mutations. AB - [This corrects the article on p. 102 in vol. 6, PMID: 25852744.]. PMID- 26284111 TI - Potential role of lncRNA cyp2c91-protein interactions on diseases of the immune system. AB - With unprecedented increase in next generation sequencing technologies, there has been a persistent interest on transcript profiles of long non-coding RNAs (lncRNAs) and protein-coding genes forming an interaction network. Apart from protein-protein interaction (PPI), gene network models such as Weighted Gene Co expression Network Analysis (WGCNA) are used to functionally annotate lncRNAs in identifying their potential disease associations. To address this, studies have led to characterizing transcript structures and understanding expression profiles mediating regulatory roles. In the current exploratory analysis, we show how a lncRNA - cyp2c91 contributes to the transcriptional regulation localized to cytoplasm thereby making refractory environment for transcription. By applying network methods and pathway analyses on genes related to a disease such as obesity and systemic lupus erythematosus, we show that we can gain deeper insight in biological processes such as the perturbances in immune system, and get a better understanding of the systems biology of diseases. PMID- 26284113 TI - Mimicking family like attributes to enable a state of personal recovery for persons with mental illness in institutional care settings. AB - BACKGROUND: The convergence between mental ill health and homelessness is well documented, but critical events that precipitate the downward spiral into homelessness, and promote personal recovery remain only partially explored in India. AIMS: To explore causative factors of the descent into homelessness, and gain insight into creative and innovative approaches that promote personal recovery, specifically in institutional care settings. METHODS: This qualitative study used focus group discussions, detailed personal interviews and anonymised data drawn from patient files. The data were analysed using phenomenological approaches. RESULTS: Findings suggest that besides poverty and deprivation, death of the primary caregiver is a critical event in precipitating distress and a breakdown in the family, leading to a loss of support systems and a sense of belongingness, and rendering persons with mental illness homeless. Social affiliations, kinship, congruence between the real and ideal self, and the drive to assume a more powerful identity and/or pursue self-actualisation emerged as key factors aiding personal recovery. In the absence of a family, mimicking its attributes appears to ground institutions and professionals in an ethos of responsiveness and user-centricity, thereby promoting personal recovery. CONCLUSIONS: This study highlights the critical need to further explore and understand the nature of distress and descent into homelessness, and gain insight into caregiver strain and strategies that can be developed to reduce the same. It further emphasizes the need to shed light on individual strategies that help pursue wellbeing, and delve deeper into the application of value frameworks in institutions and their role in promoting personal recovery among persons with mental health issues. PMID- 26284112 TI - Functional characterization of drought-responsive modules and genes in Oryza sativa: a network-based approach. AB - Drought is one of the major environmental stress conditions affecting the yield of rice across the globe. Unraveling the functional roles of the drought responsive genes and their underlying molecular mechanisms will provide important leads to improve the yield of rice. Co-expression relationships derived from condition-dependent gene expression data is an effective way to identify the functional associations between genes that are part of the same biological process and may be under similar transcriptional control. For this purpose, vast amount of freely available transcriptomic data may be used. In this study, we consider gene expression data for different tissues and developmental stages in response to drought stress. We analyze the network of co-expressed genes to identify drought-responsive genes modules in a tissue and stage-specific manner based on differential expression and gene enrichment analysis. Taking cues from the systems-level behavior of these modules, we propose two approaches to identify clusters of tightly co-expressed/co-regulated genes. Using graph centrality measures and differential gene expression, we identify biologically informative genes that lack any functional annotation. We show that using orthologous information from other plant species, the conserved co-expression patterns of the uncharacterized genes can be identified. Presence of a conserved neighborhood enables us to extrapolate functional annotation. Alternatively, we show that single 'guide-gene' approach can help in understanding tissue-specific transcriptional regulation of uncharacterized genes. Finally, we confirm the predicted roles of uncharacterized genes by the analysis of conserved cis elements and explain the possible roles of these genes toward drought tolerance. PMID- 26284114 TI - Conference report on the 28th annual meeting of the European Musculo-Skeletal Oncology Society, 29 April-1 May 2015, Athens. AB - The 28th Annual Meeting of the European Musculo-Skeletal Oncology Society was organised in Athens by the local host Professor Papagelopoulos and his team. The main objective of the meeting was to focus on recent advances in the diagnosis and treatment of bone and soft tissue sarcomas. The interdisciplinary nature of the meeting was of great value-surgeons, oncologists, pathologists, radiologists, and basic researchers discussed new strategies in the war on sarcoma. This report will highlight the major findings of this successful meeting. PMID- 26284115 TI - Breast cancer in pregnancy: an institutional experience. AB - BACKGROUND: Breast cancer is one of the most common cancers diagnosed during pregnancy. Pregnancy-associated breast cancer (PABC) is defined as breast cancer diagnosed during pregnancy or within 12 months of delivery. Nowadays PABC can be safely diagnosed, staged, and treated during pregnancy with good outcomes for both the mother and the fetus. Recent studies suggest that prognosis of women diagnosed during postpartum seems to be worse. In order to gain a better understanding of the PABC, we reviewed our centre's experience. PATIENTS AND METHODS: We assessed the clinicopathological parameters, evolution, and outcome of patients treated in the Fundacion Instituto Valenciano de Oncologia of Valencia, Spain, from October 1990 to October 2013, and compared the results of patients diagnosed during pregnancy (group 'A') and patients diagnosed within one year of delivery (group 'B'). Of 12,000 cases of breast cancer registered in our database, 35 cases of PABC were identified. We included 11 patients in group 'A' and 24 in group 'B'. RESULTS: In our group the median age was 35 years (range 29 42), of which ten (28%) patients had family history (first grade) of breast cancer, four patients were BRCA 1 mutation carriers. Axillary node compromise was found in 19 patients (53.5%), 24 patients were stage II or III at diagnosis (68.5%), 22 (62.8%) were ER positive, and nine (25.7%) were HER-2 positive. In group A (n = 11), five patients diagnosed before 18th week decided that a therapeutic abortion be performed before treatment, two patients were treated during pregnancy, one with chemotherapy without treatment associated complications during delivery. Four women diagnosed after 28th week decided to delay the treatment until delivery. After a follow up of 172 months, the relapse free survival (RFS) was 69% at five years and 45% at ten years. Overall survival (OS) at five years was 90.8% and 74.2% at ten years for all patients. For group 'A' OS was higher with 90% at five years versus 80% in group 'B'. The differences between the groups were not statistically significant p = 0.368. CONCLUSION: In our experience, there is a higher OS in patients diagnosed during pregnancy suggesting a better prognosis for this group of women but the difference between the groups is not statistically significant. Our study is limited because of our small sample. PMID- 26284116 TI - Tumour location within the breast: Does tumour site have prognostic ability? AB - INTRODUCTION: Tumour location within the breast varies with the highest frequency in the upper outer quadrant (UOQ) and lowest frequency in the lower inner quadrant (LIQ). Whether tumour location is prognostic is unclear. To determine whether tumour location is prognostic, associations between tumour site and clinicopathological characteristics were evaluated. MATERIALS AND METHODS: All patients enrolled in the Clinical Breast Care Project whose tumour site-UOQ, upper inner quadrant (UIQ), central, LIQ, lower outer quadrant (LOQ)-was determined by a single, dedicated breast pathologist were included in this study. Patients with multicentric disease (n = 122) or tumours spanning multiple quadrants (n = 381) were excluded from further analysis. Clinicopathological characteristics were analysed using chi-square tests for univariate analysis with multivariate analysis performed using principal components analysis (PCA) and multiple logistic regression. Significance was defined as P < 0.05. RESULTS: Of the 980 patients with defined tumour location, 30 had bilateral disease. Tumour location in the UOQ (51.5%) was significantly higher than in the UIQ (15.6%), LOQ (14.2%), central (10.6%), or LIQ (8.1%). Tumours in the central quadrant were significantly more likely to have higher tumour stage (P = 0.003) and size (P < 0.001), metastatic lymph nodes (P < 0.001), and mortality (P = 0.011). After multivariate analysis, only tumour size and lymph node status remained significantly associated with survival. CONCLUSIONS: Evaluation of tumour location as a prognostic factor revealed that although tumours in the central region are associated with less favourable outcome, these associations are not independent of location but rather driven by larger tumour size. Tumours in the central region are more difficult to detect mammographically, resulting in larger tumour size at diagnosis and thus less favourable prognosis. Together, these data demonstrate that tumour location is not an independent prognostic factor. PMID- 26284117 TI - Lessons from the first ecancer symposium on angiogenesis in gastric cancer. AB - In March 2015, ecancer hosted a symposium at the European Institute of Oncology in Milan, Italy on the topic of angiogenesis in gastric cancer. During this meeting, leaders in the field focused on the latest research on the topic of angiogenesis in gastric cancer, delivering lectures combined with interactive question and answer (Q & A) sessions and a roundtable discussion with the meeting's chairs. Topics covered included biomarkers, imaging, and the current state of antiangiogenic drugs in gastric cancer. This report will provide an understanding of the relevance of angiogenesis in gastric cancer research, and clinical experiences from diverse perspectives. PMID- 26284118 TI - Why does obesity promote cancer? Epidemiology, biology, and open questions. AB - The association between obesity and/or metabolic syndrome and an elevated mortality from cancer has been confirmed by an astonishing number of studies across nations and ethnicities, such that obesity is now recognised to be among the most prominent cancer risk factors worldwide. Despite this overwhelming evidence and the societal impact of obesity, we know surprisingly little about the underlying molecular mechanisms. This knowledge gap is a major obstacle to the implementation of effective lifestyle change policies. As the scientific community is insecure on what messages it should deliver, administrators are uncertain as to what exactly to recommend, and consumers are confused about whom to believe. This leaves the field flooded with pseudo-scientific recommendations that are hard to eradicate. In this review, I will provide a summary of the existing epidemiological and mechanistic evidence on the relationship between systemic metabolism and cancer, highlighting debated issues and ongoing investigations. PMID- 26284119 TI - Metabolic serum biomarkers for the prediction of cancer: a follow-up of the studies conducted in the Swedish AMORIS study. AB - The Swedish Apolipoprotein MOrtality RISk study (AMORIS) contains information on more than 500 biomarkers collected from 397,443 men and 414,630 women from the greater Stockholm area during the period 1985-1996. Using a ten-digit personal identification code, this database has been linked to Swedish national registries, which provide data on socioeconomic status, vital status, cancer diagnosis, comorbidity, and emigration. Within AMORIS, 18 studies assessing risk of overall and site-specific cancers have been published, utilising a range of serum markers representing glucose and lipid metabolism, immune system, iron metabolism, liver metabolism, and bone metabolism. This review briefly summarises these findings in relation to more recently published studies and provides an overview of where we are today and the challenges of observational studies when studying cancer risk prediction. Overall, more recent observational studies supported previous findings obtained in AMORIS, although no new results have been reported for serum fructosamine and inorganic phosphate with respect to cancer risk. A drawback of using serum markers in predicting cancer risk is the potential fluctuations following other pathological conditions, resulting in non specificity and imprecision of associations observed. Utilisation of multiple combination markers may provide more specificity, as well as give us repeated instead of single measurements. Associations with other diseases may also necessitate further analytical strategies addressing effects of serum markers on competing events in addition to cancer. Finally, delineating the role of serum metabolic markers may generate valuable information to complement emerging clinical studies on preventive effects of drugs and supplements targeting metabolic disorders against cancer. PMID- 26284121 TI - Lifestyle, nutrition and breast cancer: facts and presumptions for consideration. AB - Breast cancer is the most common cancer in women worldwide, and the high incidence of this cancer coupled with improvements in initial treatments has led to an ever-increasing number of breast cancer survivors. Among the prospective epidemiological studies on diet and breast cancer incidence and recurrence, to date, there is no association that is strong, reproducible and statistically significant, with the exception of alcohol intake, overweight, and weight gain. Nevertheless, many beliefs about food and breast cancer persist in the absence of supporting scientific evidence. After a comprehensive review regarding the role of lifestyle on breast cancer outcomes and a thorough study of the dissemination field including mass media, clinical institutions, and academic figures, we briefly reported the most common presumptions and also facts from the literature regarding lifestyle, nutrition, and breast cancer. The randomised controlled trial is the best study-design that could provide direct evidence of a causal relationship; however, there are methodological difficulties in applying and maintaining a lifestyle intervention for a sufficient period; consequently, there is a lack of this type of study in the literature. Instead, it is possible to obtain indirect evidence from observational prospective studies. In this article, it becomes clear that for now the best advice for women's health is to follow the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) recommendations on diet, nutrition, physical activity, and weight management for cancer prevention, because they are associated with a lower risk of developing most types of cancer, including breast cancer. Despite current awareness of the role of nutrition in cancer outcomes, there is inadequate translation from research findings into clinical practice. We suggest the establishment of a multidisciplinary research consortium to demonstrate the real power of lifestyle interventions. PMID- 26284120 TI - Oxidative stress and the unfulfilled promises of antioxidant agents. AB - It is well known that aging and its associated diseases, including cancer, are triggered by oxidative damage to biological macromolecules. However, antioxidant compounds are still disappointingly distant from any clinical application, so that Jim Watson has declared that antioxidant supplementation may have caused more cancers than it has prevented Watson J ((2013) Oxidants, antioxidants and the current incurability of metastatic cancers Open Biol 3 DOI: 10.1098/rsob.120144). To clarify this paradox, here, we describe the mechanisms of oxidative stress focusing in particular on redox balance and physiological oxidative signals. PMID- 26284122 TI - Pilot evaluation of physical and psychological effects of a physical trek programme including a dog sledding expedition in children and teenagers with cancer. AB - AIM OF THE STUDY: To evaluate the feasibility and to measure the effects of a six week-long adapted physical activity programme (APAP), including 5 days of intense dog sledding, on the physical and psychological health of children and adolescents treated for cancer. METHODS: Eleven children and teenagers (4 girls, 7 boys; mean age 14.3 +/- 2.9 years) participated in this monocentric pilot programme of adapted physical activities from February 2013 to March 2013. Seven were still on treatment. The programme lasted 6 weeks. A series of physical tests and psychological questionnaires were carried out before and after the programme. RESULTS: All children and teenagers completed the full programme. An improvement in all physical and psychological parameters was observed. Statistically significant differences were observed for global self-esteem (6.2 +/- 2.1 to 7.7 +/- 1.8; p = 0.02), perceived sport competence (5.3 +/- 3.2 to 7.4 +/- 2; p = 0.02) and perceived physical strength (5.6 +/- 2.5 to 7.1 +/- 1.8; p = 0.001). Regarding physical tests, the physical training led to statistically significant improvement for sit-ups (13.8 +/- 2.6 to 21.75 +/- 5.4; p = 0.01), muscle tone (76 +/- 23.7 to 100 +/- 22.9; p = 0.01), and resting heart rate (96.1 +/- 3.2 to 91.6 +/- 4.5; p = 0.03). CONCLUSION: This programme is feasible in children and adolescents even during their oncologic treatment. During the 6-week programme, children and adolescents improved their physical and psychological health, and the putative benefits of the APAP are discussed. A larger randomised trial started in 2014. PMID- 26284123 TI - Enteric-type adenocarcinoma of the lung harbouring a novel KRAS Q22K mutation with concomitant KRAS polysomy: a case report. AB - This case describes a novel KRAS Q22K mutation with simultaneous KRAS polysomy in a patient with advanced, enteric-type, adenocarcinoma of the lung. Despite the administration of systemic chemotherapy, the disease underwent rapid progression and led to the patient's death in a short period of time. Such an aggressive clinical course suggests that, in this specific case, KRAS dependency was the major genetic driver of poor prognosis. Direct deoxy ribonucleic acid (DNA) sequencing of the KRAS gene allows for the detection of novel KRAS mutations, and it might be advocated in patients with advanced non-small cell lung cancer in view of the emerging role of KRAS as a potential therapeutic target. PMID- 26284124 TI - Serum anti-p53 antibody as a tumour marker for colorectal cancer screening. AB - A 60-year-old Japanese man presented to our hospital for further investigation of an elevated serum anti-p53 antibody level. He was diagnosed with colon cancer and the tumour was surgically resected. Histological diagnosis of advanced colon cancer without lymph node involvement or distant metastasis was made. It was noteworthy that both serum carcinoembryonic antigen (CEA) and a fecal occult blood test that were performed preoperatively were non-diagnostic. This case highlights the potential usefulness of serum anti-p53 antibody tests for detection of colorectal cancers. Moreover, sequential changes in the anti-p53 antibody levels after curative resection were observed. PMID- 26284125 TI - Design of Thiol- and Light-sensitive Degradable Hydrogels using Michael-type Addition Reactions. AB - Injectable depots that respond to exogenous and endogenous stimuli present an attractive strategy for tunable, patient-specific drug delivery. Here, the design of injectable and multimodal degradable hydrogels that respond to externally applied light and physiological stimuli, specifically aqueous and reducing microenvironments, is reported. Rapid hydrogel formation was achieved using a thiol-maleimide click reaction between multifunctional poly(ethylene glycol) macromers. Hydrogel degradation kinetics in response to externally applied cytocompatible light, reducing conditions, and hydrolysis were characterized, and degradation of the gel was controlled over multiple time scales from seconds to days. Further, tailored release of an encapsulated model cargo, fluorescent nanobeads, was demonstrated. PMID- 26284126 TI - The equity of admissions to the University Hospital of Brasilia. AB - BACKGROUND: Brazil has a highly stratified population with large socioeconomic disparities, as evidenced by marked differentiation in health status and access to health services by the population. In addition, the fact that the universal national healthcare system and a liberalised private care model exist side by side leads to increasingly inequitable health outcomes. AIMS: This study aims to appraise the equity of access to the University Hospital in Brasilia, Brazil, in 2013. METHODS: This study was a quantitative analysis of hospital admissions data. The sample included all patients admitted over a six-month period in 2013. Patient data was crossed with socioeconomic data (income and private health insurance status). Frequency tabulations and chi-square calculations were used to describe the patient mix, observe trends and appraise equity of admissions. RESULTS: Analysis of the data showed that the number of patients from each neighbourhood relative to the neighbourhood population was equitable. However, when assessed on the basis of insurance status (i.e., deducting the population covered by private health insurance), a high level of inequity was detected (chi square 71.828, df 3, p<0,0001) whereby patients from wealthier neighbourhoods were overrepresented compared to those from poorer neighbourhoods. CONCLUSION: This study has shown that access to the University Hospital in Brasilia is not equitable when individual access to private healthcare is accounted for. The results show that dual access to both public and private healthcare is likely to be common, increasing some of the population's access to healthcare while decreasing access for others, and therefore contributing to inequity of access to healthcare services. PMID- 26284127 TI - Vascular disease burden in Indian subjects with vascular dementia. AB - BACKGROUND: Vascular disease factors like hypertension, diabetes mellitus, dyslipidaemia, and ischaemic heart disease contribute to the development of vascular dementia. As comorbidity of vascular disease factors in vascular dementia is common, we investigated the vascular disease burden in subjects with vascular dementia. AIMS: To investigate the vascular disease burden due to four vascular disease factors: hypertension, diabetes mellitus, dyslipidaemia, and ischaemic heart disease in Indian subjects with vascular dementia. METHODS: In this study, 159 subjects with probable vascular dementia (as per NINDS-AIREN criteria) attending the memory clinic at a tertiary care hospital were assessed for the presence of hypertension, diabetes mellitus, dyslipidaemia, and ischaemic heart disease using standardised operational definitions and for severity of dementia on the Clinical Dementia Rating (CDR) scale. The data obtained was subjected to appropriate statistical analysis. RESULTS: Dyslipidaemia (79.25 per cent) was the most common vascular disease factor followed by hypertension (73.58 per cent), ischaemic heart disease (58.49 per cent), and diabetes mellitus (40.80 per cent). Most subjects (81.1 per cent) had two or more vascular disease factors. Subjects with more severe dementia had more vascular disease factors (sig 0.001). CONCLUSION: People with moderate to severe dementia have a significantly higher vascular disease burden; therefore, higher vascular disease burden may be considered as a poor prognostic marker in vascular dementia. Subjects with vascular dementia and their caregivers must manage cognitive impairment and ADL alongside managing serious comorbid vascular diseases that may worsen the dementia. PMID- 26284128 TI - Sensitivity and specificity of CT scan in revealing skull fracture in medico legal head injury victims. AB - BACKGROUND: Emergency departments rely on CT scans to manage trauma victims, especially for head injuries. Although the detection of an undisplaced fracture on a CT scan of the head without significant intracranial findings may be insignificant for a clinician, such cases are of paramount importance for medico legal purposes because they help ascertain the nature, manner, and cause of the head injury. AIMS: The study was conducted with the objective of knowing the sensitivity and specificity of ante-mortem CT scan findings indicating the presence or absence of skull fractures. METHODS: Findings were confirmed during post-mortem examination of the subjects who had died during management but who had not had any surgical intervention. A comparative study of ante-mortem CT scan and autopsy findings with respect to fracture in traumatic head injuries was undertaken on 60 deceased individuals brought in for medico-legal post-mortem examination over a period of two years. RESULTS: Considering the autopsy findings as the gold standard, we have concluded that 14.6 per cent of the fractures were missed on CT scan findings compared to fractures found during autopsy. The sensitivity of CT scan for skull fractures was found to be 85.4 per cent and specificity was 100 per cent. Kappa was 0.787, which shows good agreement with p<0.001, which was highly significant. CONCLUSION: In developing countries, images are interpreted in the axial plane only on a CT scan of the head, which may be due to a lack of financial and human resources. For better delineation of fractures, the use of techniques like multi-detector CT with sagittal and coronal reformations should be considered in the routine interpretation of a CT scan of the head. PMID- 26284129 TI - Exploring the safety measures by doctors on after-hours house call services. AB - BACKGROUND: Aggression against doctors involved in after-hours house calls (AHHC) is widely perceived to be high. It is, however, unclear how doctors who perform this service manage the risk of aggressive patients during home visits. AIMS: The aim of this paper is to explore if and how doctors manage the risk of violence against them during AHHC. METHODS: A survey was designed and administered to all 300 Australian-based doctors engaged in AHHC under the National Home Doctor Service (NHDS). The survey was conducted from September 2014 to November 2014. RESULTS: There were 172 responses (57.3 per cent). Only 43 per cent of respondents adopted personal protective measures. The remaining 57 per cent had none; of those 6 per cent had never considered protective measures, and 31.8 per cent were aware of the risk of violence, but were unsure of what to do. Measures adopted include the use of chaperones/security personnel (34.1 per cent), dependence on surgery policies (31.2 per cent), de-escalation techniques (15.2 per cent), panic buttons (7.2 per cent), personal alarms (6.1 per cent), and others (6.5 per cent). Females were more likely to adopt personal protective measures than males (OR 4.94; p<0.01; CI 1.70-14.34), and Australian-trained doctors were less likely to do so relative to overseas-trained doctors (OR 0.35; p=0.04; CI 0.12-0.99). CONCLUSION: Just over half of the doctors involved in AHHC took no precautions against aggressive attacks while on duty, and nearly one third relied on the policies of their employing surgeries. PMID- 26284130 TI - Clinician involvement in the teaching of anatomy to medical students. PMID- 26284131 TI - The Prognostic Significance of Combining VEGFA, FLT1 and KDR mRNA Expressions in Brain Tumors. AB - Tumor cells require angiogenesis to deliver nutrients and oxygen to support their fast growth and metabolism. The vascular endothelial growth factor (VEGF) pathway plays an important role in promoting angiogenesis, including tumor-induced angiogenesis. Recent clinical trials have demonstrated the benefit of targeting VEGF in the treatment of glioblastoma. However, the prognostic significance of the expression of VEGFA and its receptors VEGFR1 (FLT1) and VEGFR2 (KDR) are still largely elusive. In the present study, we aimed to investigate the prognostic significance of these three factors, alone or in combination, in glioma patients. Gene mRNA expression was extracted from three independent brain tumor cohorts totaling 242 patients and the association between gene expression and survival was tested. We found that when VEGFA, FLT1 and KDR expressions were considered alone, only VEGFA demonstrated a significant association with patient survival. Patients with high expression of both VEGFA and either receptor had significantly worse survival than patients expressing both factors at a low level. Importantly, we found that those patients whose tumors overexpressed all three genes had a significantly shorter survival compared to those patients with a low level expression of these genes. Our results suggest that a high level expression of VEGFA and its receptors, both FLT1 and KDR, may be required for brain tumor progression, and that these three factors should be considered together as a prognostic indicator for brain tumor patients. PMID- 26284132 TI - Promoter Hypermethylation in White Blood Cell DNA and Breast Cancer Risk. AB - The role of gene-specific methylation in white blood cells (WBC) as a marker of breast cancer risk is currently unclear. We determined whether promoter hypermethylation in blood DNA of candidate tumor suppressor genes frequently methylated in breast tumors can be used as a surrogate biomarker for breast cancer risk. Promoter methylation of BRCA1, CDH1 and RARbeta was analyzed in WBC DNA from a population-based sample of 1,021 breast cancer patients and 1,036 controls by the MethyLight assay. Gene-specific promoter methylation in the DNA of 569 tumor tissue samples was also analyzed to determine the correlation of methylation levels with blood from the same individual. Hypermethylation of BRCA1 (OR: 1.31; 95% CI: 0.98-1.75) in WBC was associated with an increased risk of breast cancer when positive methylation was defined as >=0.1% methylated. There was lack of concordance between tumor tissue and paired WBC DNA methylation. These results provide limited support that hypermethylation of BRCA1 in WBC DNA may be useful for determination of breast cancer risk. Additional studies with larger numbers of genes are needed to fully understand the relationship between WBC methylation and breast cancer risk. PMID- 26284133 TI - Hypothesis: Obesity Is Associated with a Lower Mutation Threshold in Colon Cancer. AB - Neoplastic progression requires accumulation of several mutations (mutation threshold). We hypothesize that obesity raises the risk of microsatellite stable (MSS) colon cancer (CC) at least in part by decreasing the mutation threshold. Thus, we posit that obese patients require fewer mutations, particularly driver mutations, compared to their normal BMI counterparts. Further, we suggest that the reduced number of required mutations in obese patients could be due to several factors, including the high levels of cytokines that accompany obesity. Cytokine-activated ERK, AKT, and JAK/STAT signaling could synergize with CC initiating mutations to promote intestinal neoplastic development. Therefore, driver mutations that induce these specific pathways may not be "required" for neoplastic development in obesity; alteration in cell signaling consequent to obesity can substitute for some driver mutations in neoplastic progression. This hypothesis is supported by preliminary analyses of data from The Cancer Genome Atlas (TCGA). Thus, we observed that, compared to normal weight patients, cancer genomes of obese MSS CC patients exhibit fewer somatic mutations, and correspondingly lower numbers of mutations in driver genes (P = 0.026).The most striking observation was the lower number of KRAS mutations detected in patients with high body-mass index (BMI). These intriguing observations require further validation with increased number of patients, taking into account all possible confounding factors. If the hypothesis is confirmed, future studies should also address several possible explanations for the observed lower mutation threshold in obese MSS CC patients. PMID- 26284134 TI - Genetic Characterization of Ten-Eleven-Translocation Methylcytosine Dioxygenase Alterations in Human Glioma. AB - The molecular mechanisms leading to brain tumors still remain unclear. Nevertheless, there is increasing evidence that epigenetic effects play crucial roles in tumor development and progression. Thereby, 5-hydroxymethylcytosine (5hmC) represents a further base modification of cytosine besides 5 methylcytosine (5mC). In addition to the role of 5hmC as an intermediate in demethylation, 5hmC is of reasonable importance for cellular control. Previous studies showed that loss of 5hmC is a hallmark of human malignancies, e.g. in glioma, melanoma, and myeloid tumors. In myeloid malignancies studies showed that loss of 5hmC was due to mutations within ten-eleven-translocation (TET) genes, enzymes being responsible for conversion of 5mC to 5hmC. Nevertheless, till date there are no genetic characterization data of TET enzymes available for glioma. In this study, we genetically characterized TET2 and TET3 alterations in 50 human gliomas (WHO-Grade II-IV) and in 19 healthy brain samples. We identified 7 genetic alterations within TET2 (p.V218M, p.G355N, p.P363L, p.L1721W, p.P1723S, p.I1762V, p.H1778R). Additionally, we performed quantification of 5hmC amount and added functional prediction analysis of identified TET alterations to evaluate the biological impact of these alterations on the hydroxymethylome. An analysis of TET3 showed no non-synonymous alterations. In summary, we did not find correlations of TET alterations with 5hmC amount. Thus, our data emphasize that, in contrast to leukemia, loss of 5hmC in glioma is not caused by TET gene alterations. Moreover, other disturbances, such as disrupted gene expressions or functional inhibitions of TET proteins may be responsible for the aberrant epigenome of human glioma. PMID- 26284135 TI - Vasculature Disruption Enhances Bacterial Targeting of Autochthonous Tumors. AB - Attenuated Salmonella enterica serovar Typhimurium (S. Typhimurium) has been developed as a vector to deliver therapeutic agents to tumors. The potential of S. Typhimurium in cancer therapy is largely due to its reported propensity to accumulate at greater than 1,000-fold higher concentrations in tumors relative to healthy tissues. In this study, we compared bacterial colonization of tumors in a subcutaneous transplantation model with a more clinically relevant autochthonous tumor model. Following intravenous administration of attenuated S. Typhimurium strain SL3261, we observed approximately 10,000-fold less bacteria in autochthonous tumors that sporadically develop in transgenic BALB-neuT mice compared to tumors developed from subcutaneous transplantation of 4T1 murine breast cancer cells in BALB/c mice. Treatment of BALB-neuT mice with a vasculature-disrupting agent (VDA) prior to bacterial treatment caused necrosis of tumor tissue and significantly increased the bacterial targeting of autochthonous tumors by approximately 1,000-fold. These observations emphasize the importance of appropriate model selection in developing bacteria-based cancer therapies and demonstrate the potential of combining VDA pre-treatment with bacteria to facilitate targeting of clinically relevant tumors. PMID- 26284136 TI - Regulative Effect of Nampt on Tumor Progression and Cell Viability in Human Colorectal Cancer. AB - Colorectal cancer (CRC) is the third most common cancer disease. Here we examined Nampt expression in patients with CRC and the effect of Nampt on cell viability in CRC cells. Nampt protein was overexpressed in colorectal adenoma as well as colorectal carcinoma. The immunoreactive staining of Nampt was negative in the adjacent normal colorectal tissue, weak in colorectal adenoma, and strong in colorectal carcinoma, which may represent tumor progression. Further evaluation of clinical data showed that Nampt expression was not correlated with the clinicopathological characteristics of CRC. Additionally, our in vitro studies demonstrated that Nampt promotes CRC cell viability, whereas the Nampt inhibitor FK866 suppressed CRC cell viability, which was in concordance with the previous studies in other cancer cells. Treatment with Nampt-siRNA reduced the Nampt protein expression resulting in the inhibition of the cell viability of HCT116 and Caco2. Thus, the involvement of Nampt in cell growth indicates that Nampt may play an important role in colorectal tumorigenesis. As a consequence, our results suggest that Nampt may be considered as a progression marker of colorectal tumor and a potentially therapeutic target for the treatment of CRC. PMID- 26284137 TI - Ethnodrama: An Innovative Knowledge Translation Tool in the Management of Lymphedema. AB - BACKGROUND: Lymphedema can cause significant physical impairment and quality-of life issues. Yet there is a gap in knowledge about lymphedema among breast cancer survivors (BCS), and health care professionals (HCP). Ethnodrama is an innovative knowledge translation strategy that uses theatrical performances for dissemination of research results. We evaluated the impact of live ethnodrama on HCP' and BCS' awareness and attitudes in relation to impact of lymphedema on BCS' lives. METHODS: Ethnodrama performances were developed by script writers and a theatre director in collaboration with the investigators and BCS using data from published research and pre-performances workshops. Six interactive live performances were given to audiences of BCS, HCP, and community members in four cities across Canada. After watching these live performances, members of the audiences were asked to complete a paper-based questionnaire regarding their knowledge of lymphedema, and their attitudes and practices toward lymphedema. RESULTS: Of 238 audience members who participated in the survey, 55 (23%) were BCS and 85 (37.5%) were HCP. Most members rated the performances as very effective in changing their (84%) or other people's (93%) understanding of lymphedema; 96% reported being motivated to seek additional information on lymphedema, and 72% of HCP anticipated changes in their practices related to lymphedema screening. Overall no significant differences were noted in responses to ethnodrama between BCS and HCP. Open-ended responses were supportive of the findings from the closed-ended questions. CONCLUSIONS: Our results indicate that ethnodrama performances effectively convey information and positively affecting changes in HCP' and BCS' attitudes toward lymphedema. PMID- 26284138 TI - Differential Targeting of Stem Cells and Differentiated Glioblastomas by NK Cells. AB - We have recently shown that Natural Killer (NK) cells control survival and differentiation of Cancer Stem-like Cells (CSCs) through two distinct phenotypes of cytotoxic and anergic NK cells, respectively. In this report, brain CSCs and their serum and NK cell differentiated counterparts were studied. Serum differentiated brain CSCs were significantly less susceptible to NK cells and CTL direct cytotoxicity as well as NK cell mediated Antibody Dependent Cellular Cytotoxicity (ADCC), whereas their CSCs were highly susceptible. The levels of CD44 and EGFR were higher in brain tumor CSCs when compared to the serum differentiated tumors. No differences could be observed for the expression of MHC class I between brain tumor stem cells and their serum-differentiated counterparts. Moreover, supernatants from the combination of IL-2 and anti CD16mAb treated NK cells (anergized NK cells) induced resistance of brain tumor CSCs to NK cell mediated cytotoxicity. Unlike serum-differentiated CSCs, NK supernatant induced differentiation and resistance to cytotoxicity in brain CSCs correlated with the increased expression of CD54 and MHC class I. The addition of anti-MHC class I antibody moderately inhibited NK mediated cytotoxicity against untreated or serum-differentiated CSCs, whereas it increased cytotoxicity against NK supernatant differentiated tumors. Therefore, two distinct mechanisms govern serum and NK supernatant mediated differentiation of brain tumors. PMID- 26284140 TI - Efficacy of the Additional Neoadjuvant Chemotherapy to Concurrent Chemoradiotherapy for Patients with Locoregionally Advanced Nasopharyngeal Carcinoma: a Bayesian Network Meta-analysis of Randomized Controlled Trials. AB - BACKGROUND: Due to the lack of studies, it remains unclear whether the additional neoadjuvant chemotherapy (NACT) to concurrent chemoradiotherapy (CCRT) is superior to CCRT alone for locoregionally advanced nasopharyngeal carcinoma (NPC). The main objective of this Bayesian network meta-analysis was to determine the efficacy of NACT+CCRT as compared with CCRT alone. METHODS: We comprehensively searched databases and extracted data from randomized controlled trials involving NPC patients who received NACT+CCRT, CCRT, NACT+radiotherapy (RT), or RT. Overall survival (OS) with hazard ratio (HR), and locoregional recurrence rate (LRR) and distant metastasis rate (DMR) with relative risks (RRs), were concerned. RESULTS: Nine trials involving 1988 patients were analyzed. In the network meta-analysis, there was significant benefit of NACT+CCRT over CCRT for DMR (RR=0.54, 95% credible interval [CrI]=0.27-0.94). However, NACT+CCRT had a tendency to worsen locoregional control significantly as compared with CCRT (RR =1.71, 95%CrI =0.94-2.84), and no significant improvement in OS was found (HR =0.73, 95%CrI=0.40-1.23). CONCLUSIONS: NACT+CCRT is associated with reduced distant failure as compared with CCRT alone, and whether the additional NACT can improve survival for locoregionally advanced NPC should be further explored. Optimizing regimens and identifying patients at high risk of metastasis may enhance the efficacy of NACT+CCRT. PMID- 26284139 TI - Argonaute 2: A Novel Rising Star in Cancer Research. AB - AGO2 (Argonaute 2, EIF2C2) is the only member in AGO family with catalytic activity and of extreme importance during small RNAs guided gene silencing processes. The structural investigations have provided insights into details and functional mechanisms of the four major domains within AGO2. As a multifunction player, AGO2 has been revealed involved in tumorgenesis through miRNAs-dependent or independent ways. And nowadays, AGO2 has also been more importantly found ectopically over-expressed in carcinomas and closely associated with aspects of cancers in means of interacting with well-known tumor factors. Here, we provide a review on structural insights, functional mechanisms, novel roles and relationship with carcinomas of AGO2. PMID- 26284141 TI - GOLPH3L is a Novel Prognostic Biomarker for Epithelial Ovarian Cancer. AB - OBJECTIVE: Golgi phosphoprotein 3 (GOLPH3) is a highly conserved membrane protein that is involved in a variety of cancers such as colorectal cancer, gastric cancer, ovarian cancer, and breast cancer. GOLPH3L is a paralog of GOLPH3. Although these proteins share a similar amino acid sequence, much less is known regarding the subcellular functions or effects of GOLPH3L on cancer compared with GOLPH3. The role of GOLPH3L in epithelial ovarian cancer (EOC) has not yet been investigated. METHODS: Using western blot, PCR and immunohistochemical analyses, we studied the clinical significance of GOLPH3L expression in EOC. The correlations between GOLPH3L expression and the clinicopathological variables of patients with EOC were assessed using Pearson's chi2 test. Kaplan-Meier analysis was used to compare the postoperative survival between groups of patients with EOC with varying levels of GOLPH3L expression. RESULTS: High expression of GOLPH3L was more frequently observed in EOC tissues than in corresponding adjacent non-tumor tissues. The expression of GOLPH3L correlated closely with pre operative CA125 level (P=0.031). Univariate analysis showed that age, FIGO stage, pre-operative cancer antigen (CA) 125, pre-operative albumin concentration (AC), optimal cytoreductive surgery (CRS) and GOLPH3L expression correlate significantly with overall survival (OS). Multivariate analysis revealed that GOLPH3L expression was an independent prognostic factor for OS of patients with EOC (102 months versus 72 months; P=0.013). What's more, knocked down of GOLPH3L with small interfering RNA (siRNA) technology of OVCAR3 and SKOV3 cell lines reduced cell viability obviously, compared to the negative control and blank control groups. CONCLUSIONS: Our data show that increased expression of GOLPH3L is associated with poor prognosis of patients with EOC and may act as a novel, useful and independent prognostic indicator. Therefore, further studies are warranted. PMID- 26284142 TI - Initiate Tumors with Single Cell Spheres Formed in Serum-Containing Medium. AB - Background : It is difficult to prospectively identify and maintain putative tumor-initiating cells (TICs). Spheres that formed in serum-free media contained more TICs while spheres formed in serum-containing media were not used in tumor initiating. Methods : Soft-agar was used to isolate colonies. A continuous, static suspension culture using serum-containing media was modified from liquid overlay technique and tumor cell spheres could be maintained by this method for >90 days. Tumor-initiating capacity of these spheres was tested in nude mice. The nuclear staining of OCT4 in sphere cells and the expression profile of hepatic cell lineage related genes were examined. Results : Soft-agar derived HepG2 colonies indicated different properties from their parental cells. The suspension cells of A549 and MCF7 could initiate tumors at 10(4) cells level. The growth proportions of individual A549, MCF7 and HepG2 spheres with diameter of 101-150 um were significantly higher than smaller spheres. After suspension culture for 15-27 days, HepG2 and MCF7 spheres could initiate tumors with diameter up to 200 um; the estimated TIC frequency was 1/1500-1/400. The HepG2 and MCF7 spheres retain tumor-initiating potential for at least 52 days. Conclusion : After 15 days' serum-containing suspension culture small HepG2 and MCF7 cell spheres (diameter ~200 um) could initiate tumors in nude mice. PMID- 26284143 TI - Association between Dietary Vitamin C Intake and Risk of Prostate Cancer: A Meta analysis Involving 103,658 Subjects. AB - We attempted to systematically determine the association between dietary intake of vitamin C and risk of prostate cancer. PubMed and Embase were searched to obtain eligible studies published before February 2015. Cohort or case-control studies that reported the relative risk (RR)/odds ratio (OR) estimates with 95% confidence intervals (CIs) for the association between vitamin C intake and prostate cancer risk were included. Eighteen studies regarding dietary vitamin C intake were finally obtained, with a total of 103,658 subjects. The pooled RR of prostate cancer for the highest versus the lowest categories of dietary vitamin C intake was 0.89 (95%CI: 0.83-0.94; p = 0.000) with evidence of a moderate heterogeneity (I(2) = 39.4%, p = 0.045). Meta-regression analysis suggested that study design accounted for a major proportion of the heterogeneity. Stratifying the overall study according to study design yielded pooled RRs of 0.92 (95%CI: 0.86-0.99, p = 0.027) among cohort studies and 0.80 (95%CI: 0.71-0.89, p = 0.000) among case-control studies, with no heterogeneity in either subgroup. In the dose response analysis, an inverse linear relationship between dietary vitamin C intake and prostate cancer risk was established, with a 150 mg/day dietary vitamin C intake conferred RRs of 0.91 (95%CI: 0.84-0.98, p = 0.018) in the overall studies, 0.95 (95%CI: 0.90-0.99, p = 0.039) in cohort studies, and 0.79 (95%CI: 0.69-0.91, p = 0.001) in case-control studies. In conclusion, intake of vitamin C from food was inversely associated with prostate cancer risk in this meta-analysis. PMID- 26284144 TI - Manganese (II) Chelate Functionalized Copper Sulfide Nanoparticles for Efficient Magnetic Resonance/Photoacoustic Dual-Modal Imaging Guided Photothermal Therapy. AB - The integration of diagnostic and therapeutic functionalities into one nanoplatform shows great promise in cancer therapy. In this research, manganese (II) chelate functionalized copper sulfide nanoparticles were successfully prepared using a facile hydrothermal method. The obtained ultrasmall nanoparticles exhibit excellent photothermal effect and photoaoustic activity. Besides, the high loading content of Mn(II) chelates makes the nanoparticles attractive T1 contrast agent in magnetic resonance imaging (MRI). In vivo photoacoustic imaging (PAI) results showed that the nanoparticles could be efficiently accumulated in tumor site in 24 h after systematic administration, which was further validated by MRI tests. The subsequent photothermal therapy of cancer in vivo was achieved without inducing any observed side effects. Therefore, the copper sulfide nanoparticles functionalized with Mn(II) chelate hold great promise as a theranostic nanomedicine for MR/PA dual-modal imaging guided photothermal therapy of cancer. PMID- 26284145 TI - Structure-based Design of Peptides with High Affinity and Specificity to HER2 Positive Tumors. AB - To identify peptides with high affinity and specificity against human epidermal growth factor receptor 2 (HER2), a series of peptides were designed based on the structure of HER2 and its Z(HER2:342) affibody. By using a combination protocol of molecular dynamics modeling, MM/GBSA binding free energy calculations, and binding free energy decomposition analysis, two novel peptides with 27 residues, pep27 and pep27-24M, were successfully obtained. Immunocytochemistry and flow cytometry analysis verified that both peptides can specifically bind to the extracellular domain of HER2 protein at cellular level. The Surface Plasmon Resonance imaging (SPRi) analysis showed that dissociation constants (K D) of these two peptides were around 300 nmol/L. Furthermore, fluorescence imaging of peptides against nude mice xenografted with SKBR3 cells indicated that both peptides have strong affinity and high specificity to HER2 positive tumors. PMID- 26284146 TI - A Quick Responsive Fluorogenic pH Probe for Ovarian Tumor Imaging. AB - A novel cell-permeable compound, CypH-1, that is non-fluorescent at neutral pH, but fluoresces under mildly acidic conditions with a near infrared maximum emission wavelength was designed for the detection of tumors in the clinical setting. The potential of CypH-1 in ovarian cancer imaging was demonstrated using a murine model. The intraperitoneally administered CypH-1 results in a robust fluorescence signal of discrete neoplastic lesions with millimeter range resolution within few hours. Moreover, fluorescence signal is strikingly enhanced at peripheral regions of tumors at the microscopic level suggesting a sharp physiological difference at the tumor/normal tissue interface. This robust acid activated imaging agent is expected to have significant impact in broad surgical and diagnostic applications. PMID- 26284147 TI - Neural systems mediating processing of sound units of language distinguish recovery versus persistence in stuttering. AB - BACKGROUND: Developmental stuttering is a multi-factorial disorder. Measures of neural activity while children processed the phonological (language sound unit) properties of words have revealed neurodevelopmental differences between fluent children and those who stutter. However, there is limited evidence to show whether the neural bases of phonological processing can be used to identify stuttering recovery status. As an initial step, we aimed to determine if differences in neural activity during phonological processing could aid in distinguishing children who had recovered from stuttering and those whose stuttering persisted. METHODS: We examined neural activity mediating phonological processing in forty-three 7-8 year old children. Groups included children who had recovered from stuttering (CWS-Rec), those whose stuttering persisted (CWS-Per), and children who did not stutter (CWNS). All children demonstrated normal non verbal intelligence and language skills. Electroencephalograms were recorded as the children listened to pairs of pseudo-words (primes-targets) that either rhymed or did not. Behavioral rhyme judgments along with peak latency and mean amplitude of the N400s elicited by prime and target stimuli were examined. RESULTS: All the groups were very accurate in their rhyme judgments and displayed a typical ERP rhyme effect, characterized by increased N400 amplitudes over central parietal sites for nonrhyming targets compared to rhyming targets. However, over anterior electrode sites, an earlier onset of the N400 for rhyming compared to non-rhyming targets, indexing phonological segmentation and rehearsal, was observed in the CWNS and CWS-Rec groups. This effect occurred bilaterally for the CWNS, was greater over the right hemisphere in the CWS-Rec, and was absent in the CWS-Per. CONCLUSIONS: These results are the first to show that differences in ERPs reflecting phonological processing are marked by atypical lateralization in childhood even after stuttering recovery and more pronounced atypical neural patterns for the children whose stuttering persisted. Despite comparable language and phonological skills as revealed by standardized tests, the neural activity mediating phonological segmentation and rehearsal differentiated 7-8 year old children whose stuttering persisted from those who had recovered from stuttering and typically developing peers. PMID- 26284148 TI - Diabetic patients' willingness to use tele-technology to manage their disease - A descriptive study. AB - OBJECTIVES: Diabetes mellitus is a public health concern worldwide. TeleHealth technology may be an effective tool for empowering patients in the self management of diabetes mellitus. However despite the great impact of diabetes on healthcare in Saudi Arabia, no research has investigated diabetic patients' willingness to use this technology. This study investigates diabetic patients' willingness to use tele-technology as a tool to monitor their disease. METHODS: Data were collected from diabetic patients attending the diabetes education clinic at the Ministry of National Guard Health Affairs (MNGHA) in the Eastern region of Saudi Arabia over a three month period. A survey was developed which measured patients' willingness to use tele-technology in the self-management of their diabetes as well as their perceived expectations from the technology. RESULTS: The study found that the majority of patients were willing to use tele technology to self- monitor their diabetes. However, a minority (11.3%) indicated willingness to use the system daily and only half indicated preference to use it once a week (53.8%). Patients who were younger, had higher education levels, were employed, had internet access and had Type II diabetes were significantly more likely to report willingness to use the technology. CONCLUSIONS: Diabetic patients could be ready to play a more active role in their care if given the opportunity. Results from this study could serve as a baseline for future studies to develop targeted interventions by trialing tele-technology on a sample of the diabetic population. Patients with diabetes need to be in charge of their own care in order to improve health outcomes across the country. PMID- 26284149 TI - Enhancing health policymakers' information literacy knowledge and skill for policymaking on control of infectious diseases of poverty in Nigeria. AB - BACKGROUND: In Nigeria, one of the major challenges associated with evidence-to policy link in the control of infectious diseases of poverty (IDP), is deficient information literacy knowledge and skill among policymakers. There is need for policymakers to acquire the skill to discover relevant information, accurately evaluate retrieved information and to apply it correctly. OBJECTIVES: To use information literacy tool of International Network for Availability of Scientific Publications (INASP) to enhance policymakers' knowledge and skill for policymaking on control of IDP in Nigeria. METHODS: Modified "before and after" intervention study design was used in which outcomes were measured on target participants both before the intervention is implemented and after. This study was conducted in Ebonyi State, south-eastern Nigeria and participants were career health policy makers. A two-day health-policy information literacy training workshop was organized to enhance participants" information literacy capacity. Topics covered included: introduction to information literacy; defining information problem; searching for information online; evaluating information; science information; knowledge sharing interviews; and training skills. RESULTS: A total of 52 policymakers attended the workshop. The pre-workshop mean rating (MNR) of knowledge and capacity for information literacy ranged from 2.15-2.97, while the post-workshop MNR ranged from 3.34-3.64 on 4-point scale. The percentage increase in MNR of knowledge and capacity at the end of the workshop ranged from 22.6%-55.3%. CONCLUSION: The results of this study suggest that through information literacy training workshop policy makers can acquire the knowledge and skill to identify, capture and share the right kind of information in the right contexts to influence relevant action or a policy decision. PMID- 26284150 TI - Virtual communities of practice: can they support the prevention agenda in public health? AB - BACKGROUND: Virtual Communities of Practice (CoPs) are flexible communication and knowledge management tools enabling collaboration, sharing of best practice and professional development. There have been few studies that have looked at the use and usefulness of virtual CoPs in public health. METHODS: This project sought to gather the evidence and develop recommendations for the value of virtual CoPs in public health through a literature review, and through piloting two CoPs in obesity. The research aimed to find out how useful CoPs are in obesity prevention, what makes a CoP successful and what evaluation methods are appropriate. RESULTS: CoPs are composed of observers, passive and active contributors with a small group of 'super-users'. All users learn through reading and listening, even if they do not post. The CoPs had higher levels of reading activity as opposed to low levels of posting activity. Longer existence of CoPs usually means more active membership. There are complex reasons why users fail to engage in knowledge sharing. Success of a CoP is creating an online environment where users feel comfortable. CoPs need administrative support and facilitation. Champions play a vital role. CONCLUSIONS: Evidence shows some encouraging results about the value of CoPs in enabling collaboration and information sharing. Despite low membership numbers of the obesity CoPs piloted, members see value and suggest improvements. Findings suggest that success comes from leadership, champions, and larger networks with more posting activity. Mixed methods of quantitative and qualitative research are appropriate in measuring the use and impact of CoPs. PMID- 26284151 TI - The limited effect of information on Israeli pregnant women at advanced maternal age who decide to undergo amniocentesis. AB - BACKGROUND: A primary goal of amniocentesis is the detection of trisomy 21 (Down syndrome- DS) in the fetus. This procedure involves a small risk of miscarriage. As the risk of DS increases with maternal age, screening tests (maternal serum triple test and others) and age are used to generate a risk assessment, and amniocentesis is offered to women with high risk. In Israel, amniocentesis is government funded for women of advanced maternal age (AMA, i.e., >=35 years), even if their risk assessment is low. The purpose of this study was to explore the reasons AMA women undergo amniocentesis, their knowledge about risk estimates, and to evaluate whether their decision is informed. METHODS: Shortly after undergoing amniocentesis, 42 consecutive women without a medical indication for amniocentesis other than age, completed a questionnaire that assessed their knowledge and opinions regarding screening tests, pregnancy termination, amniocentesis risks and the factors that affected their decision. RESULTS: Women rarely deliberated before undergoing amniocentesis. One third of those who had the screening test did not wait for the results before undergoing amniocentesis. Only one third of those who received the screening results remembered their risk estimation before going ahead with amniocentesis. Almost half (41 %) cited "age" as their main reason for undergoing amniocentesis, though only 44 % of these women could recall their age related DS risk. Sixty percent estimated their DS risk as low or very low but still had amniocentesis. Most participants (74 %) stated that they would consider termination of the pregnancy if the fetus was diagnosed with an intellectual deficit. CONCLUSIONS: These results cast doubt on whether AMA women's decision to undergo amniocentesis is based on risk estimates, as women seem to disregard risk estimates, and sometimes not even wait for them when making the decision. The policy of funding amniocentesis solely on the basis of age may have led to the conception that being over 35 alone is sufficient reason to undergo amniocentesis. This finding should inform policy makers, as it raises questions about the link between public funding and the choices of individual women, and has implications for healthcare expenditures. PMID- 26284152 TI - ASSURE-CSU: a real-world study of burden of disease in patients with symptomatic chronic spontaneous urticaria. AB - BACKGROUND: Chronic spontaneous urticaria (CSU) formerly known as chronic idiopathic urticaria (CIU) is a severe and distressing skin condition that remains uncontrolled in approximately one half of patients, despite the use of licensed, recommended doses of modern, second-generation H1-antihistamines. So far, the humanistic, societal and economic burden of CSU/CIU has not been well quantified. Therefore it is important to broaden our understanding of how CSU/CIU impacts patients, society, and healthcare systems, by determining the disease burden of CSU/CIU and the associated unmet need; as well as to further guide the use of new treatments in an efficient and cost-effective manner. METHODS: ASSURE CSU is an observational, multicenter study being conducted in the UK, Germany, Canada, France, Italy, Spain, and The Netherlands. The study comprises a retrospective medical chart review in conjunction with patient surveys (including validated tools for assessment of disease impact) and an 8-day patient diary. The primary objectives of the study are to describe patient demographics, medical history, treatments, and healthcare resource utilization based on medical-record data and to assess the impact of disease, healthcare resource utilization, work days missed, and productivity loss based on patient-reported data. Approximately 700 patients (aged >=18 years) will be enrolled who have CSU/CIU despite currently receiving treatment, and have had persistent symptoms for at least 12 months. Data will be collected retrospectively for the 12 months (+/-1 month) prior to enrolment wherever possible, and prospectively for the week following enrolment. DISCUSSION: ASSURE-CSU will be the first study to examine the economic and humanistic burden of disease in patients diagnosed with CSU/CIU who are symptomatic despite treatment. By combining retrospective evaluation of medical records with prospective patient surveys and 8-day diaries, across seven different countries, the ASSURE-CSU study will contribute to a better understanding and acknowledgement of the burden of disease in patients with symptomatic chronic spontaneous urticaria. PMID- 26284154 TI - Investigation of scanning parameters for thyroid fine needle aspiration cytology specimens: A pilot study. AB - BACKGROUND: Interest in developing more feasible and affordable applications of virtual microscopy in the field of cytology continues to grow. AIMS: The aim of this study was to investigate the scanning parameters for the thyroid fine needle aspiration (FNA) cytology specimens. SUBJECTS AND METHODS: A total of twelve glass slides from thyroid FNA cytology specimens were digitized at *40 with 1 micron (MU) interval using seven focal plane (FP) levels (Group 1), five FP levels (Group 2), and three FP levels (Group 3) using iScan Coreo Au scanner (Ventana, AZ, USA) producing 36 virtual images (VI). With an average wash out period of 2 days, three participants diagnosed the preannotated cells of Groups 1, 2, and 3 using BioImagene's Image Viewer (version 3.1) (Ventana, Inc., Tucson, AZ, USA), and the corresponding 12 glass slides (Group 4) using conventional light microscopy. RESULTS: All three raters correctly identified and showed complete agreement on the glass and VI for: 86% of the cases at FP Level 3, 83% of the cases at both the FP Levels 5 and 7. The intra-observer concordance between the glass slides and VI for all three raters was highest (97%) for Level 3 and glass, same (94%) for Level 5 and glass; and Level 7 and glass. The inter rater reliability was found to be highest for the glass slides, and three FP levels (77%), followed by five FP levels (69.5%), and seven FP levels (69.1%). CONCLUSIONS: This pilot study found that among the three different FP levels, the VI digitized using three FP levels had slightly higher concordance, intra observer concordance, and inter-rater reliability. Scanning additional levels above three FP levels did not improve concordance. We believe that there is no added benefit of acquiring five FP levels or more especially when considering the file size, and storage costs. Hence, this study reports that FP level three and 1 MU could be the potential scanning parameters for the thyroid FNA cytology specimens. PMID- 26284155 TI - Smartphone applications: A contemporary resource for dermatopathology. AB - INTRODUCTION: Smartphone applications in medicine are becoming increasingly prevalent. Given that most pathologists and pathology trainees today use smartphones, an obvious modality for pathology education is through smartphone applications. "MyDermPath" is a novel smartphone application that was developed as an interactive reference tool for dermatology and dermatopathology, available for iOS and Android. MATERIALS AND METHODS: "MyDermPath" was developed using Apple Xcode and Google Android SDK. Dermatology images (static and virtual slides) were annotated and configured into an algorithmic format. Each image comprised educational data (diagnosis, clinical information, histopathology, special stains, differential diagnosis, clinical management, linked PubMed references). Added functionality included personal note taking, pop quiz, and image upload capabilities. A website was created (http://mydermpath.com) to mirror the app. RESULTS: The application was released in August 2011 and updated in November 2013. More than 1,100 reference diagnoses, with over 2,000 images are available via the application and website. The application has been downloaded approximately 14,000 times. The application is available for use on iOS and Android platforms. CONCLUSIONS: Smartphone applications have tremendous potential for advancing pathology education. "MyDermPath" represents an interactive reference tool for dermatology and dermatopathologists. PMID- 26284153 TI - Association between serum alkaline phosphatase and primary resistance to erythropoiesis stimulating agents in chronic kidney disease: a secondary analysis of the HERO trial. AB - BACKGROUND: Erythropoiesis stimulating agent (ESA)-resistant anemia is common in chronic kidney disease (CKD). OBJECTIVES: To evaluate the determinants of severity of ESA resistance in patients with CKD and primary ESA-resistance. DESIGN: Secondary analysis of a randomized controlled trial (the Handling Erythropoietin Resistance with Oxpentifylline, HERO). SETTING AND PATIENTS: 53 adult patients with CKD stage 4 or 5 and primary ESA-resistant anemia (hemoglobin <=120 g/L, ESA resistance index [ERI] >=1.0 IU/kg/week/gHb for erythropoietin or >=0.005 MUg/kg/week/gHb for darbepoeitin, no cause for ESA-resistance identified). MEASUREMENTS: Iron studies, parathyroid hormone, albumin, liver enzymes, phosphate or markers of oxidative stress and inflammation. METHODS: Participants were divided into tertiles of ERI. Multinomial logistic regression was used to analyse the determinants of ERI tertiles. RESULTS: All patients, except one, were receiving dialysis for end-stage kidney disease. The mean +/- SD ERI values in the low (n = 18), medium (n = 18) and high (n = 17) ERI tertiles were 1.4 +/- 0.3, 2.3 +/- 0.2 and 3.5 +/- 0.8 IU/kg/week/gHb, respectively (P < 0.001). There were no significant differences observed in age, gender, ethnicity, cause of kidney disease, diabetes, iron studies, parathyroid hormone, albumin, liver enzymes, phosphate or markers of oxidative stress and inflammation between the ERI tertiles. The median [inter-quartile range] serum alkaline phosphatase concentrations in the low, medium and high ERI tertiles were 89 [64,121], 99 [76,134 and 148 [87,175] U/L, respectively (P = 0.054). There was a weak but statistically significant association between ERI and serum alkaline phosphatase (R(2) = 0.06, P = 0.03). Using multinomial logistic regression, the risk of being in the high ERI tertile relative to the low ERI tertile increased with increasing serum alkaline phosphatase levels (P = 0.02). No other variables were significantly associated with ERI. LIMITATIONS: Small sample size; bone-specific alkaline phosphatase, other markers of bone turnover and bone biopsies not evaluated. CONCLUSIONS: Serum alkaline phosphatase was associated with severity of ESA resistance in ESA-resistant patients with CKD. Large prospective studies are required to confirm this association. ( TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry 12608000199314). PMID- 26284156 TI - Use of a data warehouse at an academic medical center for clinical pathology quality improvement, education, and research. AB - BACKGROUND: Pathology data contained within the electronic health record (EHR), and laboratory information system (LIS) of hospitals represents a potentially powerful resource to improve clinical care. However, existing reporting tools within commercial EHR and LIS software may not be able to efficiently and rapidly mine data for quality improvement and research applications. MATERIALS AND METHODS: We present experience using a data warehouse produced collaboratively between an academic medical center and a private company. The data warehouse contains data from the EHR, LIS, admission/discharge/transfer system, and billing records and can be accessed using a self-service data access tool known as Starmaker. The Starmaker software allows users to use complex Boolean logic, include and exclude rules, unit conversion and reference scaling, and value aggregation using a straightforward visual interface. More complex queries can be achieved by users with experience with Structured Query Language. Queries can use biomedical ontologies such as Logical Observation Identifiers Names and Codes and Systematized Nomenclature of Medicine. RESULT: We present examples of successful searches using Starmaker, falling mostly in the realm of microbiology and clinical chemistry/toxicology. The searches were ones that were either very difficult or basically infeasible using reporting tools within the EHR and LIS used in the medical center. One of the main strengths of Starmaker searches is rapid results, with typical searches covering 5 years taking only 1-2 min. A "Run Count" feature quickly outputs the number of cases meeting criteria, allowing for refinement of searches before downloading patient-identifiable data. The Starmaker tool is available to pathology residents and fellows, with some using this tool for quality improvement and scholarly projects. CONCLUSION: A data warehouse has significant potential for improving utilization of clinical pathology testing. Software that can access data warehouse using a straightforward visual interface can be incorporated into pathology training programs. PMID- 26284157 TI - The Treatment of Distal Radius Fractures in the Elderly. PMID- 26284159 TI - Influence of playing standard and physical fitness on activity profiles and post match fatigue during intensified junior rugby league competition. AB - BACKGROUND: The aim of this study was to determine whether the fatigue responses to the same intensified rugby league competition differed depending on playing standard and physical fitness. METHODS: Players from a high-standard (n = 15) and a low-standard (n = 16) junior rugby league team had lower body neuromuscular fatigue, perceptual wellbeing, and blood creatine kinase (CK) assessed over an intensified competition. Global positioning system units measured match activity profiles and rating of perceived exertion-assessed internal loads. Players were divided into high- and low-fitness groups across the two standards based on Yo-Yo intermittent recovery test performance. RESULTS: Playing intensity increased with playing standard and fitness levels (high-standard = 92 +/- 6 m.min-1 vs. 88 +/- 6 m.min-1; low-standard = 88 +/- 2 m.min-1 vs. 83 +/- 6 m.min-1). Despite greater internal and external loads, high-fitness players showed smaller reductions in lower body power (high-standard effect size [ES] = -0.74; low-standard ES = 0.41). High-standard players had smaller increases in blood CK (77% +/- 94% vs. 113% +/- 81%; ES = -0.41), primarily due to very small increases in the high fitness group (50% +/- 45%). CONCLUSIONS: Increased fitness leads to greater internal and external workloads during intensified competition, smaller increases in blood CK, and less neuromuscular fatigue. Maximising player fitness should be a primary goal of coaches in order to increase match workloads and reduce post match fatigue during intensified competition. KEY POINTS: Increased physical fitness results in greater relative and absolute match workloads.Increased physical fitness results in less fatigue and muscle damage during an intensified competition.Coaching staff should aim to maximise physical fitness in order to optimise match performance and reduce player fatigue. PMID- 26284158 TI - Strength training in soccer with a specific focus on highly trained players. AB - BACKGROUND: Data concerning the physical demands of soccer (e.g., activity pattern) suggest that a high level of performance requires well-developed neuromuscular function (NF). Proficient NF may be relevant to maintain and/or increase players' short- (intense periods of soccer-specific activity; accelerations, decelerations, and sprinting) and long-term performance during a match and throughout the season. OBJECTIVE: This review examines the extent to which distinct modes of strength training improve soccer players' performance, as well as the effects of concurrent strength and endurance training on the physical capacity of players. DATA SOURCES: A selection of studies was performed in two screening phases. The first phase consisted of identifying articles through a systematic search using relevant databases, including the US National Library of Medicine (PubMed), MEDLINE, and SportDiscus. Several permutations of keywords were utilized (e.g., soccer; strength; power; muscle function), along with the additional scanning of the reference lists of relevant manuscripts. Given the wide range of this review, additional researchers were included. The second phase involved applying six selection criteria to the articles. RESULTS AND CONCLUSIONS: After the two selection phases, 24 manuscripts involving a total sample of 523 soccer players were considered. Our analysis suggests that professional players need to significantly increase their strength to obtain slight improvements in certain running-based actions (sprint and change of direction speed). Strength training induces greater performance improvements in jump actions than in running-based activities, and these achievements varied according to the motor task [e.g., greater improvements in acceleration (10 m) than in maximal speed (40 m) running movements and in non-squat jump (SJ) than in SSC-based actions (countermovement jump)]. With regard to the strength/power training methods used by soccer players, high-intensity resistance training seems to be more efficient than moderate-intensity resistance training (hypertrophic). From a training frequency perspective, two weekly sessions of strength training are sufficient to increase a player's force production and muscle power-based actions during pre-season, with one weekly session being adequate to avoid in season detraining. Nevertheless, to further improve performance during the competitive period, training should incorporate a higher volume of soccer specific power-based actions that target the neuromuscular system. Combined strength/power training programs involving different movement patterns and an increased focus on soccer-specific power-based actions are preferred over traditional resistance exercises, not only due to their superior efficiency but also due to their ecological value. Strength/power training programs should incorporate a significant number of exercises targeting the efficiency of stretch shortening-cycle activities and soccer-specific strength-based actions. Manipulation of training surfaces could constitute an important training strategy (e.g., when players are returning from an injury). In addition, given the conditional concurrent nature of the sport, concurrent high-intensity strength and high-intensity endurance training modes (HIT) may enhance a player's overall performance capacity. Our analysis suggests that neuromuscular training improves both physiological and physical measures associated with the high-level performance of soccer players. PMID- 26284160 TI - Response of oxidative stress and inflammatory biomarkers to a 12-week aerobic exercise training in women with metabolic syndrome. AB - BACKGROUND: Evidences have been highlighted the relationship among metabolic syndrome, chronic low-grade inflammation, oxidative stress and several diseases. In this sense, the aim of this study was to investigate the effects of aerobic exercise training on oxidative stress and inflammatory parameters on women with metabolic syndrome (MS). METHODS: Twenty-three untrained women (51.86 +/- 6.58 years old, BMI 30.8 +/- 4.3 kg/m2) completed a 12-week treadmill exercise training, without modifications on dietary pattern. Advanced oxidation protein products (AOPP), thiobarbituric acid-reactive substances (TBARS), total thiol content (T-SH) and nitrite and nitrate (NOx) levels were assessed in plasma while the levels of interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were evaluated in the serum. The RNA expression (mRNA) of IL-1beta, IL-10, TNF alpha, IFN-gamma, insulin receptor substrate 2 (IRS-2) and matrix metalloproteinase-9 (MMP-9) were performed inperipheral blood mononuclear cells (PBMC) of a subset with eight women with MS using real real-time polymerase chain reaction (qPCR). RESULTS: The intervention resulted in decreased serum levels of IL-1beta, IL-6, TNF-alpha, IFN-gamma, AOPP and TBARS, besides increased levels of IL-10 and T-SH (P < 0.001). NOx concentrations were unchanged, similarly to mRNA expressions quantified in PBMC. CONCLUSIONS: Twelve weeks of AT improved systemic oxidative stress and inflammatory biomarkers in women with MS, although PBMC mRNA expression for inflammatory pathways appeared to be unchanged. This may indicate that AT induced beneficial effects not only in physical fitness but also on health promotion through decreased oxidative damage and proinflammatory status. PMID- 26284161 TI - Preventive effects of regular physical exercise against cognitive decline and the risk of dementia with age advancement. AB - With age advancement, cognitive function is impaired and the risk of dementia is increased under the influence of normal or pathological cortical and subcortical neuronal alterations. Significant researches has been undertaken to analyze the preventive effects of exercise against the decline of cognitive function and the risk of dementia (e.g., Alzheimer's disease), particularly during the past 10 years. The aim of this short review is to report the scientific knowledge, relating to these effects, that has been obtained during the past 10 years. Acute physical exercise raises the cardiac output in response to increased needs for oxygen and energetic substrates compared to the state of rest, which increases the cerebral blood flow. The increased cerebral blood flow triggers various neurobiological mechanisms in the brain tissue. Repeated and regular physiological modifications related to exercise facilitate the synthesis of cerebral tissue. Regular physical exercise (rPE) may thus increase angiogenesis, neurogenesis, synaptogenesis, and the synthesis of neurotransmitters in different cerebral structures involved in cognition due to an increase in the liberation of neurotrophic factors and the production of enzymatic antioxidants. There is an inversely proportional relationship between the amount of physical activity undertaken and the risk of cognitive decline and/or the development of neurodegenerative disease. The synthesis of cerebral tissue under the influence of aerobic rPE may increase the volume of the gray and white matters of the prefrontal and temporal cortical areas as well as the volume of the hippocampus. Moreover, coordination exercise stimulates cognitive function, thereby inducing positive adaptations of cerebral function when regularly practiced. The possible effects of other types of exercise that weakly stimulate the cardiovascular system or cognitive function, such as stretching and strength training, are also beneficial but their mechanistic explanations require further exploration. PMID- 26284162 TI - Bra strap orientations and designs to minimise bra strap discomfort and pressure during sport and exercise in women with large breasts. AB - BACKGROUND: Bra straps are a primary source of discomfort during sport and exercise, particularly for women with large breasts. This study aimed to investigate the effects of altering bra strap orientation and design on bra strap comfort, pressure and breast support in women with large breasts. This is a descriptive laboratory study. METHODS: Bra strap discomfort (visual analogue scale, 0 to 10), pressure (custom-designed 10 mm2 calibrated pressure sensor, 0.5 to 24 kPa range, 50 Hz, S2011, Novel GmbH, Munich, Germany, placed under the right bra strap at the crest of each participant's shoulder), preference ranking and vertical breast displacement (VBD; Optotrak Certus(r) motion capture system, 200 Hz, Northern Digital, Ontario, Canada) data during dynamic treadmill running and static upright standing (pressure only) were collected for 23 active women with large breasts (D+ cup size) while they wore an encapsulation sports bra with six different bra strap conditions (two bra strap orientations: vertical and cross-back; three bra strap designs: standard width, wide and gel). RESULTS: Bra strap discomfort was significantly less (p <= 0.001) in the vertical compared to the cross-back strap orientation, which was the most preferred orientation despite no significant difference in strap pressure. The wide strap design had the lowest discomfort scores, significantly lower strap pressure compared to the standard width and gel strap designs (p < 0.001), and was equally the most preferred design with the gel straps. There was no significant difference in VBD among the six strap conditions. CONCLUSIONS: Bra straps that are vertically orientated and wide (approximately 4.5 cm in width) are preferable for women with large breasts during sport and exercise to minimise bra strap pressure and discomfort. The addition of gel pads under bra straps may also decrease discomfort and prevent straps slipping off the shoulders, although this notion warrants further investigation. PMID- 26284163 TI - The impact of trunk impairment on performance of wheelchair activities with a focus on wheelchair court sports: a systematic review. AB - BACKGROUND: Trunk impairment seems to impact significantly on performance in wheelchair court sports, but evidence to support this impression has never been systematically assessed. The objective of this study is to systematically review, describe and synthesise the literature investigating the impact of trunk impairment on wheelchair activities in court sports. METHODS: This systematic review was performed according to the consensus statement for the meta-analysis of observational studies in epidemiology (MOOSE). The search strategy for original articles comprised Medline (1950- November 2014), Cinahl (1981-November 2014), and Embase (1980- November 2014), using the search terms: trunk, trunk muscles, postural balance, posture and wheelchair. Eligibility criteria for further review were 1) participants included experienced wheelchair users, 2) comparisons were made between a) participants with different levels of trunk impairment or b) between able bodied participants and participants with trunk impairment, or c) between participants with trunk impairment with and without compensatory equipment, and 3) outcome measures were quantitative data on wheelchair activities. For methodological quality assessment, the STROBE (Strengthening the reporting of observational studies in epidemiology) checklist was used. RESULTS: After assessment of 358 potentially relevant studies for the eligibility criteria, 25 studies were appropriate for methodological assessment. Twelve articles fulfilled the predetermined minimum of 15 reported items on the 22-item STROBE checklist. These studies were limited to observational studies with small populations. All but one study were restricted to patients with spinal cord injury (SCI). CONCLUSIONS: Limited evidence was found about the impact of trunk impairment on wheelchair activities. Reach to the front and multidirectional reach was further in able bodied persons than in persons with SCI. In a perturbation that equals deceleration in wheelchair court sports, able bodied persons maintain balance, whereas persons with SCI lose balance. No evidence was found to support a difference in acceleration between persons with partial trunk muscle strength and persons with full trunk muscle strength. For future research, there is a need for a test that includes all types of trunk impairment and identification of activities that determine performance in wheelchair court sports. Furthermore, populations of athletes with all trunk impairment types should be included. PMID- 26284164 TI - Synchronized personalized music audio-playlists to improve adherence to physical activity among patients participating in a structured exercise program: a proof of-principle feasibility study. AB - BACKGROUND: Preference-based tempo-pace synchronized music has been shown to reduce perceived physical activity exertion and improve exercise performance. The extent to which such strategies can improve adherence to physical activity remains unknown. The objective of the study is to explore the feasibility and efficacy of tempo-pace synchronized preference-based music audio-playlists on adherence to physical activity among cardiovascular disease patients participating in a cardiac rehabilitation. METHODS: Thirty-four cardiac rehabilitation patients were randomly allocated to one of two strategies: (1) no music usual-care control and (2) tempo-pace synchronized audio-devices with personalized music playlists + usual-care. All songs uploaded onto audio-playlist devices took into account patient personal music genre and artist preferences. However, actual song selection was restricted to music whose tempos approximated patients' prescribed exercise walking/running pace (steps per minute) to achieve tempo-pace synchrony. Patients allocated to audio-music playlists underwent further randomization in which half of the patients received songs that were sonically enhanced with rhythmic auditory stimulation (RAS) to accentuate tempo pace synchrony, whereas the other half did not. RAS was achieved through blinded rhythmic sonic-enhancements undertaken manually to songs within individuals' music playlists. The primary outcome consisted of the weekly volume of physical activity undertaken over 3 months as determined by tri-axial accelerometers. Statistical methods employed an intention to treat and repeated-measures design. RESULTS: Patients randomized to personalized audio-playlists with tempo-pace synchrony achieved higher weekly volumes of physical activity than did their non music usual-care comparators (475.6 min vs. 370.2 min, P < 0.001). Improvements in weekly physical activity volumes among audio-playlist recipients were driven by those randomized to the RAS group which attained weekly exercise volumes that were nearly twofold greater than either of the two other groups (average weekly minutes of physical activity of 631.3 min vs. 320 min vs. 370.2 min, personalized audio-playlists with RAS vs. personalized audio-playlists without RAS vs. non music usual-care controls, respectively, P < 0.001). Patients randomized to music with RAS utilized their audio-playlist devices more frequently than did non-RAS music counterparts (P < 0.001). CONCLUSIONS: The use of tempo-pace synchronized preference-based audio-playlists was feasibly implemented into a structured exercise program and efficacious in improving adherence to physical activity beyond the evidence-based non-music usual standard of care. Larger clinical trials are required to validate these findings. TRIAL REGISTRATION: ClinicalTrials.gov ID (NCT01752595). PMID- 26284165 TI - Muscle Cramping During a 161-km Ultramarathon: Comparison of Characteristics of Those With and Without Cramping. AB - BACKGROUND: This work sought to identify characteristics differing between those with and without muscle cramping during a 161-km ultramarathon. METHODS: In this observational study, race participants underwent body weight measurements before, during, and after the race; completed a post-race questionnaire about muscle cramping and "near" cramping (controllable, not reaching full-blown cramping), drinking strategies, and use of sodium supplementation during four race segments; and underwent a post-race blood draw for determination of serum sodium and blood creatine kinase (CK) concentrations. RESULTS: The post-race questionnaire was completed by 280 (74.5 %) of the 376 starters. A post-race blood sample was provided by 181 (61.1 %) of the 296 finishers, and 157 (53.0 %) of finishers completed the post-race survey and also provided a post-race blood sample. Among those who completed the survey, the prevalence of cramping and near cramping was 14.3 and 26.8 %, respectively, with greatest involvement being in the calf (54 %), quadriceps (44 %), and hamstring (33 %) muscles. Those with cramping or near cramping were more likely to have a prior history of muscle cramping during an ultramarathon (p < 0.0001) and had higher blood CK concentrations (p = 0.001) than those without cramping. Weight change during the race, use of sodium supplements, intake rate of sodium in supplements, and post-race serum sodium concentration did not differ between those with and without cramping. CONCLUSIONS: Muscle cramping is most common in those with a prior history of cramping and greater muscle damage during an ultramarathon, suggesting an association with relative muscular demand. Impaired fluid and sodium balance did not appear to be an etiology of muscle cramping during an ultramarathon. PMID- 26284166 TI - Single parent status and children's objectively measured level of physical activity. AB - BACKGROUND: Single-parent family status has been investigated as a possible psychosocial determinant of children's level of physical activity (PA)-although with mixed and inconclusive results. Prevailing evidence of the importance of two parent family status as a resource for children's PA is based on a mix of subjective and objective measurements of PA. Objectives: To investigate if the level of PA among children living with a single parent was lower compared to children living with two parents by means of a meta-analysis of published and unpublished studies. We restricted our analysis to studies with objective measurements of PA. METHODS: Data sources: The databases, Social Science Citation Index, PsycINFO, PubMed, and EBSCO were searched (1987-2013). Study eligibility criteria: Observational studies comparing objectively measured PA between single parent children and children from two-parent families. Study appraisal and synthesis methods: We used guidelines from the Cochrane Handbook of Systematic Reviews of Interventions and a modified version of the Newcastle-Ottawa Scale overall to assess the quality of the included studies. We refrained from calculation of summary scores. RESULTS: Twelve studies met the following inclusion criteria of which six were unpublished: (a) child age (6-18 years) and (b) objectively measured level of PA. Meta-analysis revealed pooled estimates of 0.01 for boys (95 % CI -0.04-0.03, p = 0.77, I2 = 6.5 %, p = 0.38) and 0.01 for girls (95 % CI -0.03-0.04, p = 0.62, I2 = 21.0 %, p = 0.24), respectively. Estimates show no differences in objectively measured physical activity between children living in single-parent families compared to children living with two parents. Analyses investigating seven potential moderators did not yield any statistical significant effect size estimates. No evidence of heterogeneity between studies was observed. Limitations: Retrieved articles were assessed by several of the authors. Blinding of the authors was not feasible, as most of the authors have been involved in the studies. CONCLUSIONS: No evidence was found suggesting that children of single-parent families are in special need of extraordinary measures to facilitate their level of PA. PMID- 26284167 TI - Evaluation of Global Health in Master Swimmers Involved in French National Championships. AB - BACKGROUND: Swimming is often recommended as a means of increasing physical activity and gaining health benefits. The present study examined the psychological, social, and physical health states in competitive swimmers engaged in long-term training. METHODS: The study took place during the 4 days of the French master championships in France in 2011 (from 10 to 13 March). Global health parameters were evaluated and compared with general values reported in studies aiming to describe health standard values in France or Europe. All swimmers selected for the event were invited to participate in the study. Setting questionnaires concerning mental and social health (short form 36), physical activity (International Physical Activity Questionnaire), and medication were administered. Peak expiratory flow (l.min-1) was measured, and body mass index (kg.m-2) was calculated from height (m) and body mass (kg). Prevalence of overweight and obesity was calculated by age and gender. Chi-squared tests were used to compare prevalence of overweight and obesity between participants and reference values. Short form 36 scores and physical activity (met.h.week-1) were compared with reference values by single t-tests. Two-way ANOVA was used to compare peak flow results with standard values. The level of significance was set at p < 0.05. RESULTS: Out of 1554 master swimmers, 490 participated in this study (rates of participation = 44.8 and 23.5 % for females and males, respectively). Data showed inequality of health indexes as compared with reference values, despite a significantly higher level of physical activity including swimming activity. The prevalence of obesity was significantly lower (p < 0.05), and peak expiratory flow values were higher among female swimmers (from 7.6 to 17 % higher according to the age, p < 0.05). Perception of vitality was significantly higher for all female swimmers and the older age groups of male swimmers (p < 0.05). Perception of bodily pain indicated significantly lower scores for swimmers than the reference values (p < 0.05). Significantly lower prevalence of swimmers taking medication was noted in comparison with the French national values (p = 0.012). CONCLUSIONS: Compared with reference data from various sources, master competitive swimmers used less medication, had lower rates of obesity in most age groups, had greater peak expiratory flow values suggesting improved lung function, had higher levels of total physical activity, and had more favorable scores for various subscales of the SF-36. The results argue in favor of competitive swimming for its positive effects on health outcomes. KEY POINTS: French master swimmers involved in national championships have many positive health outcomes in terms of weight management, respiratory function, and vitality. However, the very high physical activity level in this competitive context did not result in significantly better levels on all parameters in comparison with their national counterparts (pain perception, social, emotional, and mental health).Positive health outcomes were higher for female master swimmers in terms of weight management, respiratory function, and vitality.The fact that these benefits were not linked with medication consumption could be interesting in an economic context aimed at controlling expenditures on health. Based on these data, we can argue for promoting this form of physical activity across the lifespan. PMID- 26284168 TI - ACTN3 Polymorphism: Comparison Between Elite Swimmers and Runners. AB - BACKGROUND: The human ACTN3 gene encodes alpha-actinin-3, an actin-binding protein with a pivotal role in muscle structure and metabolism. A common genetic single nucleotide polymorphism (SNP) at codon 577 of the ACTN3 results in the replacement of an arginine (R) with a stop codon (X). The R allele is a normal functional version of the gene, whereas the X allele contains a sequence change that completely stops production of functional alpha-actinin-3 protein. The ACTN3 R577X polymorphism was found to be associated with power athletic performance especially among track and field athletes. The aim of the current study was to compare allelic and genotype frequencies of the ACTN3 R577X polymorphism among runners and swimmers specializing in different distances, and >non-athletic controls. METHODS: One hundred and thirty-seven runners, 91 swimmers and 217 controls, participated in the study. Runners were assigned to two subgroups according to their event specialty-long-distance runners (LDR) and short-distance runners (SDR). Swimmers were also assigned to two subgroups according to their main swimming event-long-distance swimmers (LDS) and short-distance swimmers (SDS). Genomic DNA was extracted from peripheral EDTA-treated anti-coagulated blood using a standard protocol. Genotypes were determined using the Taqman allelic discrimination assay. RESULTS: Runners' genotype and allele differed significantly between LDR, SDR, and controls, with the lowest prevalence of RR genotype and R allele among LDR. XX genotype and X allele prevalence was significantly higher among LDR compared to the other groups (p < 0.01 for all). On the other hand, swimmers' genotype and allele frequencies did not differ significantly between subgroups (LDS and SDS). Yet, LDS had significantly higher RR genotype and R allele frequencies compared to LDR. CONCLUSIONS: The findings suggest that while ACTN3 R577X polymorphism is a genetic polymorphism that may distinguish between SDR and LDR, it cannot differentiate significantly between SDS and LDS. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01319032. KEY POINTS: ACTN3 R577X polymorphism is largely associated with running events specialization, with high prevalence of RR genotype and R allele frequency among short-distance runners compare to long-distance runners.Unlike in running, ACTN3 R577X polymorphism is not associated with swimming specialization.The inability of the ACTN3 R577X polymorphism to distinguish between swimmers specializing in different events, presumably since other factors such as body physique, technique, tactics, etc., are more likely to determine such a distinction. PMID- 26284169 TI - Regulation of Blood Glucose Concentration in Type 1 Diabetics Using Single Order Sliding Mode Control Combined with Fuzzy On-line Tunable Gain, a Simulation Study. AB - Diabetes is considered as a global affecting disease with an increasing contribution to both mortality rate and cost damage in the society. Therefore, tight control of blood glucose levels has gained significant attention over the decades. This paper proposes a method for blood glucose level regulation in type 1 diabetics. The control strategy is based on combining the fuzzy logic theory and single order sliding mode control (SOSMC) to improve the properties of sliding mode control method and to alleviate its drawbacks. The aim of the proposed controller that is called SOSMC combined with fuzzy on-line tunable gain is to tune the gain of the controller adaptively. This merit causes a less amount of control effort, which is the rate of insulin delivered to the patient body. As a result, this method can decline the risk of hypoglycemia, a lethal phenomenon in regulating blood glucose level in diabetics caused by a low blood glucose level. Moreover, it attenuates the chattering observed in SOSMC significantly. It is worth noting that in this approach, a mathematical model called minimal model is applied instead of the intravenously infused insulin-blood glucose dynamics. The simulation results demonstrate a good performance of the proposed controller in meal disturbance rejection and robustness against parameter changes. In addition, this method is compared to fuzzy high-order sliding mode control (FHOSMC) and the superiority of the new method compared to FHOSMC is shown in the results. PMID- 26284170 TI - Analysis of Fundus Fluorescein Angiogram Based on the Hessian Matrix of Directional Curvelet Sub-bands and Distance Regularized Level Set Evolution. AB - This paper presents a new procedure for automatic extraction of the blood vessels and optic disk (OD) in fundus fluorescein angiogram (FFA). In order to extract blood vessel centerlines, the algorithm of vessel extraction starts with the analysis of directional images resulting from sub-bands of fast discrete curvelet transform (FDCT) in the similar directions and different scales. For this purpose, each directional image is processed by using information of the first order derivative and eigenvalues obtained from the Hessian matrix. The final vessel segmentation is obtained using a simple region growing algorithm iteratively, which merges centerline images with the contents of images resulting from modified top-hat transform followed by bit plane slicing. After extracting blood vessels from FFA image, candidates regions for OD are enhanced by removing blood vessels from the FFA image, using multi-structure elements morphology, and modification of FDCT coefficients. Then, canny edge detector and Hough transform are applied to the reconstructed image to extract the boundary of candidate regions. At the next step, the information of the main arc of the retinal vessels surrounding the OD region is used to extract the actual location of the OD. Finally, the OD boundary is detected by applying distance regularized level set evolution. The proposed method was tested on the FFA images from angiography unit of Isfahan Feiz Hospital, containing 70 FFA images from different diabetic retinopathy stages. The experimental results show the accuracy more than 93% for vessel segmentation and more than 87% for OD boundary extraction. PMID- 26284171 TI - Discriminative Common Spatial Pattern Sub-bands Weighting Based on Distinction Sensitive Learning Vector Quantization Method in Motor Imagery Based Brain computer Interface. AB - Common spatial pattern (CSP) is a method commonly used to enhance the effects of event-related desynchronization and event-related synchronization present in multichannel electroencephalogram-based brain-computer interface (BCI) systems. In the present study, a novel CSP sub-band feature selection has been proposed based on the discriminative information of the features. Besides, a distinction sensitive learning vector quantization based weighting of the selected features has been considered. Finally, after the classification of the weighted features using a support vector machine classifier, the performance of the suggested method has been compared with the existing methods based on frequency band selection, on the same BCI competitions datasets. The results show that the proposed method yields superior results on "ay" subject dataset compared against existing approaches such as sub-band CSP, filter bank CSP (FBCSP), discriminative FBCSP, and sliding window discriminative CSP. PMID- 26284172 TI - Detection and classification of Breast Cancer in Wavelet Sub-bands of Fractal Segmented Cancerous Zones. AB - Recent studies on wavelet transform and fractal modeling applied on mammograms for the detection of cancerous tissues indicate that microcalcifications and masses can be utilized for the study of the morphology and diagnosis of cancerous cases. It is shown that the use of fractal modeling, as applied to a given image, can clearly discern cancerous zones from noncancerous areas. In this paper, for fractal modeling, the original image is first segmented into appropriate fractal boxes followed by identifying the fractal dimension of each windowed section using a computationally efficient two-dimensional box-counting algorithm. Furthermore, using appropriate wavelet sub-bands and image Reconstruction based on modified wavelet coefficients, it is shown that it is possible to arrive at enhanced features for detection of cancerous zones. In this paper, we have attempted to benefit from the advantages of both fractals and wavelets by introducing a new algorithm. By using a new algorithm named F1W2, the original image is first segmented into appropriate fractal boxes, and the fractal dimension of each windowed section is extracted. Following from that, by applying a maximum level threshold on fractal dimensions matrix, the best-segmented boxes are selected. In the next step, the segmented Cancerous zones which are candidates are then decomposed by utilizing standard orthogonal wavelet transform and db2 wavelet in three different resolution levels, and after nullifying wavelet coefficients of the image at the first scale and low frequency band of the third scale, the modified reconstructed image is successfully utilized for detection of breast cancer regions by applying an appropriate threshold. For detection of cancerous zones, our simulations indicate the accuracy of 90.9% for masses and 88.99% for microcalcifications detection results using the F1W2 method. For classification of detected mictocalcification into benign and malignant cases, eight features are identified and utilized in radial basis function neural network. Our simulation results indicate the accuracy of 92% classification using F1W2 method. PMID- 26284173 TI - Comparison of the Absorbed Dose for (99m)Tc-Diethylenetriaminepentaacetic Acid and (99m)Tc-Ethylenedicysteine Radiopharmaceuticals using Medical Internal Radiation Dosimetry. AB - The aim of this study was the investigation of absorbed dose to the kidneys, spleen, and liver during technetium-99 m ethylene dicysteine and technetium-99 m diethylenetriaminepentaacetic acid ((99m)Tc-EC and (99m)Tc-DTPA) kidney scan. Patients who had been prepared for the kidney scan, were divided into two groups (Groups 1 and 2). The first group (Group 1) and the second group (Group 2) received intravenous injection of (99m)Tc-EC and (99m)Tc-DTP, respectively. A certain amount of radiopharmaceuticals was injected into each patient and was immediately imaged with dual-head gamma camera to calculate the activity through the conjugated view method. Then, the doses of kidney, liver, and spleen were measured using medical internal radiation dosimetry method. Finally, absorbed dose of these organs was compared. Based on these different results (P < 0.05), organs absorbed dose was significantly less with radiopharmaceutical (99m)Tc-EC as compared with (99m)Tc-DTPA. PMID- 26284174 TI - The Effects of Fenugreek on Radiation Induced Toxicity for Human Blood T-Cells in Radiotherapy. AB - Many cellular damages either in normal or cancerous tissues are the outcome of molecular events affected by ionizing radiation. T-cells are the most important among immune system agents and are used for biological radiation dose measurement in recommended standard methods. The herbs with immune modulating properties may be useful to reduce the risk of the damages and subsequently the diseases. The T cells as the most important immune cells being targeted for biological dosimetry of radiation. This study proposes a flowcytometric-method based on fluorescein isothiocyanate- and propidium iodide (PI)-labeled annexin-V to assess apoptosis in blood T-cells after irradiation in both presence and absence of fenugreek extract. T-cells peripheral blood lymphocyte isolated from blood samples of healthy individuals with no irradiated job background. The media of cultured cells was irradiated 1-h after the fenugreek extract was added. The number of apoptotic cells was assessed by annexin-V protocol and multicolor flowcytometry. An obvious variation in apoptotic cells number was observed in presence of fenugreek extract (>80%). The results suggest that fenugreek extract can potentiate the radiation induced apoptosis or radiation toxicity in blood T-cells (P < 0.05). PMID- 26284175 TI - Fully Automated Complementary DNA Microarray Segmentation using a Novel Fuzzy based Algorithm. AB - DNA microarray is a powerful approach to study simultaneously, the expression of 1000 of genes in a single experiment. The average value of the fluorescent intensity could be calculated in a microarray experiment. The calculated intensity values are very close in amount to the levels of expression of a particular gene. However, determining the appropriate position of every spot in microarray images is a main challenge, which leads to the accurate classification of normal and abnormal (cancer) cells. In this paper, first a preprocessing approach is performed to eliminate the noise and artifacts available in microarray cells using the nonlinear anisotropic diffusion filtering method. Then, the coordinate center of each spot is positioned utilizing the mathematical morphology operations. Finally, the position of each spot is exactly determined through applying a novel hybrid model based on the principle component analysis and the spatial fuzzy c-means clustering (SFCM) algorithm. Using a Gaussian kernel in SFCM algorithm will lead to improving the quality in complementary DNA microarray segmentation. The performance of the proposed algorithm has been evaluated on the real microarray images, which is available in Stanford Microarray Databases. Results illustrate that the accuracy of microarray cells segmentation in the proposed algorithm reaches to 100% and 98% for noiseless/noisy cells, respectively. PMID- 26284176 TI - Noise Estimation in Electroencephalogram Signal by Using Volterra Series Coefficients. AB - The Volterra model is widely used for nonlinearity identification in practical applications. In this paper, we employed Volterra model to find the nonlinearity relation between electroencephalogram (EEG) signal and the noise that is a novel approach to estimate noise in EEG signal. We show that by employing this method. We can considerably improve the signal to noise ratio by the ratio of at least 1.54. An important issue in implementing Volterra model is its computation complexity, especially when the degree of nonlinearity is increased. Hence, in many applications it is urgent to reduce the complexity of computation. In this paper, we use the property of EEG signal and propose a new and good approximation of delayed input signal to its adjacent samples in order to reduce the computation of finding Volterra series coefficients. The computation complexity is reduced by the ratio of at least 1/3 when the filter memory is 3. PMID- 26284177 TI - Injectable Cartilage Shaving: An Autologous and Long Lasting Filler Material for Correction of Minor Contour Deformities in Rhinoplasty. AB - BACKGROUND: Filler materials are gaining popularity in nonsurgical rhinoplasty the major advantages are the ability to camouflage the surface deformities, and also the soft and malleable consistency; while the major drawback of the safe fillers such as hyaluronic acid is short durability. In this study, we evaluated the injectable cartilage shaving as an autologous filler material for correction of minor contour deformities in rhinoplasty. METHODS: Injectable cartilage shaving was used for correction of surface irregularities in primary or secondary rhinoplasty, and long term results of 128 patients were evaluated. The source of cartilage was autologous septum, rib or less frequently, the ear concha. The material was injected with 14 to 18 gauge needles or blunted tip lipofilling cannulas with 1.3-1.7 mm internal diameters. It was performed whether during the septorhinoplasty or as a separate single procedure without elevation of the flap. Success was defined as the long term survival of the graft in the desired site and absence of recurrent deformity or complications such as extrusion, infection or displacement. RESULTS: Twenty seven males and 101 females underwent the procedure from May 2008 to January 2014. Mean follow up period was 31 (13-58) months. Ninety five percent of patients were satisfied or very satisfied with the results at the last follow up visits and touch up procedure was performed for the unsatisfied patients. CONCLUSION: Injectable cartilage shaving is a reliable filler to correct and camouflage the surface irregularities, and it is durable and predictable in long term follow ups. PMID- 26284178 TI - Platelet-Rich Fibrin Promotes an Accelerated Healing of Achilles Tendon When Compared to Platelet-Rich Plasma in Rat. AB - BACKGROUND: Autologous platelet concentrate has been used to improve the function and regeneration of injured tissues. Tendinopathies are common in clinical practice, although long-term treatment is required. On the basis of lead time, we compared the effect of using platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in repairing rat Achilles tendon. METHODS: The effectiveness of using PRP and PRF was evaluated after 14 and 28 postoperative days by histological analysis. The quantification of collagen types I and III was performed by Sirius red staining. Qualitatively, the data were verified with hematoxylin-eosin (H&E) staining. RESULTS: In Sirius red staining, no significant treatment differences were found between groups. Statistical difference was observed only between PRP (37.2% collagen) and the control group (16.2%) 14 days after treatment. Intra groups compared twice showed a difference for collagen I (27.8% and 47.7%) and III (66.9% and 46.0%) in the PRF group. The control group showed differences only in collagen I (14.2% and 40.9%) and no other finding was observed in the PRP group. In H&E staining, PRF showed a better cellular organization when compared to the other groups at 28 days. CONCLUSION: Our study suggests that PRF promotes accelerated regeneration of the Achilles tendon in rats, offering promising prospects for future clinical use. PMID- 26284179 TI - A New Reduction Mastopexy Design for Young Women: Snowman Pattern. AB - BACKGROUND: Many young women are satisfied with their large breasts but suffer from sagging due to heaviness. In this article; we present a novel modification of vertical scar breast reduction based on a special indication. METHODS: From January 2006 to May 2012, twenty five individual patients underwent operation using modified technique with superior pedicle and vertical scar. Young women between ages 25-35 years with voluminous breasts who requested mastopexy rather than reduction were selected for the surgery. RESULTS: The mean patient age was 30 years and body mass index (BMI) was 27.8+/-1.07 kg/m(2). Mean nipple transposition was 6.5 cm. Mean weight for resected tissue was 415 g for left and 419 g for right breast. Mean operative time was 125 minutes. Patients were followed up for 9-22 months. No serious complications encountered in consecutive patient series. The only complication was permanent wrinkling probably due to vertical closure in 5 of 25 patients which did not resolve during the follow-up period. CONCLUSION: We recommend that the Snowman design is a useful tool for superior pedicle breast reduction technique providing good projection and a short scar in selected patients. PMID- 26284180 TI - National Trends in the Use of Inpatient Hospitalization for Combined Abdominoplasty and Breast Surgery. AB - BACKGROUND: Combined procedures involving elective breast surgery at the time of abdominoplasty are frequently performed procedures in aesthetic plastic surgery. While found to be safe outpatient procedures, many surgeons elect to perform combined abdominoplasty/breast surgery as inpatient surgery. This study was performed to explore the practice of performing the combined procedure as an inpatient in the United States. METHODS: The Nationwide Inpatient Sample database was evaluated using ICD-9CM procedural codes to identify hospitalizations where patients underwent abdominoplasty combined with breast surgery. We trended the frequency of this combined procedure, and evaluated the rate of acute post operative complications, length of inpatient hospitalization, and total hospital charges. RESULTS: Between 2004 and 2011, 29,235 combined abdominoplasty/breast procedures were performed as inpatient in United States. The rate of major post operative complications in the acute hospitalization period was 1.12% and included CVA (0.02%), respiratory failure (0.6%), pneumonia (0.3%), VTE (0.1%), and myocardial infarction (0.1%). Hospitalization averaged 1.8 days and resulted in $31,177 of hospital charges. The demographics of the combined procedure transitioned as i) frequency of inpatient surgeries decreased, ii) percent of patients >50 yr increased, and iii) hospital charges increased from 2004 to 2011. CONCLUSION: A significant number of surgeons are performing combined abdominoplasty and elective breast surgery as inpatient procedures in United States. The combined surgery is safe but is associated with small risk of major post-operative complications. A short inpatient hospitalization may be beneficial for high-risk patients interested in combined procedures, but must be analyzed against the rising costs of inpatient surgery. PMID- 26284181 TI - Management of Facial Telangiectasias with Hand Cautery. AB - BACKGROUND: Facial telangiectasias are superficial cutaneous vessels that can result in noticeable aesthetical imperfections. This study presents a technique for the removal of facial telangiectasias using hand cautery. METHODS: Twenty five patients with facial telangiectasias were treated using hand cautery (Medicell Inc, Athens, Greece) during 2009-2013. Photo documentation was performed for each patient before and immediately after treatment. Treatment was performed by cauterization at 800 degrees C, delivered via a 30G tip directly to the lesions for milliseconds. RESULTS: Twenty two out of 25 patients (88%) exhibited complete resolution of telangiectasias using hand cautery. In 5 (20%) patients, single application achieved complete resolution of lesions and in 10 patients (40%) re-treatment was required after 3 weeks. Four patients (16%) required 3 consecutive treatments from which 2 patients (8%) showed slight improvement and one patient (4%) no improvement. No major complications were associated with this procedure except the formation of a white scar in two patients that became inconspicuous after 3 months. Minor complications included skin irritation and edema immediately after the treatment, which resolved within 2-3 days without intervention. CONCLUSION: Hand cautery is a very safe, effective and inexpensive tool for the treatment of facial telangiectasias. It is simple, cheap, and requires minimal training, although it is limited to the treatment of more superficial and small lesions. We believe that this technique is suitable for office based setting. The advantage of using inexpensive and portable instruments will also be beneficial in developing counties where access to more expensive equipment is limited. Results are satisfactory but more patients are needed to validate the technique. PMID- 26284182 TI - The Healing Effect of Arnebia Euchroma Ointment versus Silver Sulfadiazine on Burn Wounds in Rat. AB - BACKGROUND: Burn is still a majordevastating condition in emergency medicine departments among both genders and all age groups in all developed and developing countries, leading to physical, psychological scars and economical burden. The present study aimed to determine the healing effect of topical treatment with Arnebia euchroma on second-degree burn wound in rats. METHODS: Fifty rats were divided into 4 equal groups receiving the ointment base, normal saline (NS), standard 1% silver sulfadiazine (SSD), and 5% and 10% Arnebia euchroma ointments (AEO). The mean of burn area, percentage of wound contraction, histopathological and bacteriological assessments in the injured area were dtermined during the study. RESULTS: Average area of wound on the 10(th) day was 10.2+/-2.3, 8.4+/ 2.6, 12.4+/-2.5, 5.9+/-2.2 and 5.7+/-2 cm(2) for ointment base, NS, 1% SSD, and 5% and 10% AEO, respectively. Wound size was significantly lower in 10% AEO than 1% SSD and control groups on the 10(th) day post-burn injury. On day 11, the percentage of wound contraction in 5% and 10% AEO was 53.9%+/-14.7% and 55.9+/ 10.5% which was more than 1% SSD (15.3+/-10.8%). The collagen fibers were well formed and horizontally-oriented in 5% and 10% AEO groups when compared with other groups. CONCLUSION: Arnebia euchroma ointment was an effective treatment for healing of burn wounds in comparison with SSD and can be regarded as an alternative topical treatment for burn wounds. PMID- 26284183 TI - Clindamycin Phosphate Absorption from Nanoliposomal Formulations through Third Degree Burn Eschar. AB - BACKGROUND: It has been shown that topical nanoliposomal formulations improve burn healing process. On the other hand, it has been shown that liposomal formulations increase drug deposition in the normal skin while decrease their systemic absorption; there is not such data available for burn eschar. Present investigation studies permeation of clindamycin phosphate (CP) through burn eschar from liposomal formulations to answer this question. In this investigation, permeation of CP through fully hydrated third-degree burn eschar was evaluated using solution, normal nanoliposomes and ultradeformable nanoliposomes. METHODS: Liposomal CP were prepared by thin-film hydration and characterized in terms of size, size distribution, zeta potential, encapsulation efficiency and short-time stability. Then the effect of liposomal lipid concentration on CP absorption was investigated. RESULTS: The permeability coefficient ratio (liposome/solution) and permeation lag-time ratio (liposome/solution) of CP through burn eschar at 20 Mm lipid concentration were 0.81+/-0.21 and 1.19+/-1.30 respectively, indicating the retardation effects of liposomes. Data also showed that increasing liposomal lipid concentration from 20 to 100 mM, clindamycin permeation decreased by about 2 times. There was no difference between normal liposome and ultradeformable liposome in terms of clindamycin absorption. CONCLUSION: Nanoliposomes could decrease trans-eschar absorption of CP, in good agreement with normal skin data, and might indicate CP deposition in the eschar tissue. PMID- 26284184 TI - Outcomes of Older Adults with Burn Injury: University Clinical Center of Kosovo. AB - BACKGROUND: Advances in burn care over the past 50 years have brought about remarkable improvement in mortality rates such that survival has become an expected outcome even in patients with extensive injuries. Although these improvements have occurred in all age groups, survival in older adults still lags far behind that in younger cohorts. This study determines the outcomes of older adults with burn injury in University Clinical Center of Kosovo. METHODS: This is a retrospective study that includes 56 burn patients, older than 60 years who were admitted at the Department of Plastic Surgery, between 1 January 2004 and 31 December 2013. Data processing was done with the statistical package of Stat 3. From the statistical parameters the structural index, arithmetic median, and standard deviation were calculated. RESULTS: Fifty six burned patient older than 60 years were included during a 10-year period. Of the 56 elderly patients 29 were women and 27 were men with a mean age of 66.7 years (range, 60-85 years). The differences were not statistically significant for both genders regarding the causes of burn injury. CONCLUSION: Considering the gradual increase of the elderly population in our country based on the data of the Ministry of Public Services, an increase is expected to the incidence of burn injuries in the population of this category of our country. PMID- 26284185 TI - Giant Condyloma Acuminatum of Vulva Frustrating Treatment Challenge. AB - Giant condylomata are not usually seen nowadays in developed nations, but such cases are still seen in the under-resourced countries. Condylomata acuminata are commonly transmitted through sexual intercourse. Generally diagnosed based on their appearance. Giant condyloma acuminata also named Buschke- Lowenstein tumour (BLT) is a slow growing cauliflower-like tumor, locally aggressive and destructive, with possible malignant transformation. Common clinical treatment of anogenital warts is conservative, however, in extreme cases conservative therapy is insufficient and surgical excision is required. A case of common presentation of giant condylomata in a 50 years old, divorced, multiparous woman is presented and the literature is reviewed. She presented with 15 years history of slowly progressive vulval lesion and associated itching, contact bleeding, malodorous vaginal discharge and difficulty in walking. She had previously been treated with podophyllin and cryosurgery without success. The growth measured 30*10 cm in each side and was successfully excised with no evidence of malignancy concomitant and reconstruction also done. PMID- 26284186 TI - Successful Excision of Gynecomastia with Nipple Repositioning Technique Utilizing the Dermoglandular Flap. AB - There are many surgical techniques for treating gynecomastia. We report a new surgical technique in an adolescent with fatty glandular gynecomastia grade III, who was referred from an endocrinologist to our clinic. We excised the gynecomastia with nipple repositioning utilizing the dermoglandular flap (about 1 cm thickness and 10 cm width). After one month, no complication was detected and the patient was satisfied with his new breasts. We suggest this technique for fatty glandular gynecomastia grade III. PMID- 26284187 TI - Capsular Weakness around Breast Implant: A Non-Recognized Complication. AB - Capsular contraction is a frequent complication following breast augmentation. On the other hand, capsular weakness, a not widely recognized complication, may occur around the implant. A weak capsule allows the migration of the prosthesis to the lateral region of the thoracic region or inferiorly, towards the abdomen, due to gravitational forces. The cause of capsular weakness remains unresolved. Implant malposition, with lateral or downward displacement, breast asymmetry, improper contour, with implants moving in the pocket that compromise the aesthetic outcome of breast augmentation and require surgical correction may be different symptoms from the same clinical problem. Capsular weakness is a short or mid-term complication of breast augmentation. Most techniques aim to correct the malposition by making sutures to increase the resistance to the displacement of the implant, rearrange the structures using the capsule as flaps to remodel the envelope of the new pocket, obtaining a more stable and reliable result. In this article, four cases of displacement of breast prosthesis with capsular weakness are described and the surgical treatment that included a capsulotomy and capsulorraphy is described. PMID- 26284188 TI - Unilateral Sensation Loss of the NAC After Superomedial Pedicle Reduction Mammaplasty. PMID- 26284189 TI - Power-Assisted Liposuction (P.A.L.) Fat Harvesting for Lipofilling: The Trap Device. PMID- 26284190 TI - Revisiting the Curtis Procedure for Boutonniere Deformity Correction. PMID- 26284191 TI - Stromal Fibroblast in Age-Related Cancer: Role in Tumorigenesis and Potential as Novel Therapeutic Target. AB - Incidence of most common cancers increases with age due to accumulation of damage to cells and tissues. Stroma, the structure close to the basement membrane, is gaining increased attention from clinicians and researchers due to its increasingly, yet incompletely understood role in the development of age-related cancer. With advanced age, stroma generates a pro-tumorigenic microenvironment, exemplified by the senescence-associated secretory phenotype (SASP). Components of the SASP, such as cytokines, chemokines, and high energy metabolites are main drivers of age-related cancer initiation and sustain its progression. Our purpose is to provide insight into the mechanistic role of the stroma, with particular emphasis on stromal fibroblasts, on the development of age-related tumors. We also present evidence of the potential of the stroma as target for tumor therapy. Likewise, a rationale for age-related antitumor therapy targeting the stroma is presented. We expect to foster debate on the underlining basis of age-related cancer pathobiology. We also would like to promote discussion on novel stroma based anticancer therapeutic strategies tailored to treat the elderly. PMID- 26284193 TI - ROS Accumulation by PEITC Selectively Kills Ovarian Cancer Cells via UPR-Mediated Apoptosis. AB - Unfolded protein response (UPR) is crucial for both survival and death of mammalian cells, which is regulated by reactive oxygen species (ROS) and nutrient depletion. In this study, we demonstrated the effect of ROS-accumulation, induced by beta-phenethyl isothiocyanate (PEITC), on UPR-mediated apoptosis in ovarian cancer cells. We used ovarian cancer cell lines, PA-1 and SKOV-3, with different p53 status (wild- and null-type, respectively). PEITC caused increased ROS accumulation and inhibited proliferation selectively in ovarian cancer cells, and glutathione (GSH) depletion in SKOV-3. However, PEITC did not cause any effect in normal ovarian epithelial cells and peripheral blood mononuclear cells. After 48 h of PEITC treatment (5 MUM), apoptotic cell death was shown to increase significantly in the ovarian cancer cells and not in the normal cells. The key regulator of UPR-mediated apoptosis, CHOP/GADD153 and endoplasmic reticulum resident chaperone BiP/GRP78 were parallely up-regulated with activation of two major sensors of the UPR [PERK and ATF-6 in PA-1; PERK, and IRE1alpha in SKOV-3) in response to ROS accumulation induced by PEITC (5 MUM). ROS scavenger, N-acetyl L-cysteine (NAC), attenuated the effect of PEITC on UPR signatures (P-PERK, IRE1alpha, CHOP/GADD153, and BiP/GRP78), suggesting the involvement of ROS in UPR mediated apoptosis. Altogether, PEITC induces UPR-mediated apoptosis in ovarian cancer cells via accumulation of ROS in a cancer-specific manner. PMID- 26284192 TI - Focus on PTEN Regulation. AB - The role of phosphatase and tensin homolog on chromosome 10 (PTEN) as a tumor suppressor has been for a long time attributed to its lipid phosphatase activity against PI(3,4,5)P3, the phospholipid product of the class I PI3Ks. Besides its traditional role as a lipid phosphatase at the plasma membrane, a wealth of data has shown that PTEN can function independently of its phosphatase activity and that PTEN also exists and plays a role in the nucleus, in cytoplasmic organelles, and extracellularly. Accumulating evidence has shed light on diverse physiological functions of PTEN, which are accompanied by a complex regulation of its expression and activity. PTEN levels and function are regulated transcriptionally, post-transcriptionally, and post-translationally. PTEN is also sensitive to regulation by its interacting proteins and its localization. Herein, we summarize the current knowledge on mechanisms that regulate the expression and enzymatic activity of PTEN and its role in human diseases. PMID- 26284195 TI - Mitochondria-Associated Endoplasmic Reticulum Membranes Microenvironment: Targeting Autophagic and Apoptotic Pathways in Cancer Therapy. AB - Autophagy is a tightly regulated catabolic pathway that terminates in the lysosomal compartment after the formation of a cytoplasmic vacuole that engulfs macromolecules and organelles. Notably, autophagy is associated with several human pathophysiological conditions, playing either a cytoprotective or cytopathic role. Many studies have investigated the role of autophagy in cancer. However, whether autophagy suppresses tumorigenesis or provides cancer cells with a rescue mechanism under unfavorable conditions remains unclear. Mitochondria associated membranes (MAMs) are juxtaposed between the endoplasmic reticulum and mitochondria and have been identified as critical hubs in the regulation of apoptosis and tumor growth. One key function of MAMs is to provide asylum to a number of proteins with tumor suppressor and oncogenic properties. Accordingly, mechanistic studies during tumor progression suggest a strong involvement of these proteins at various steps of the autophagic process. This paper discusses the present state of our knowledge about the intimate molecular networks between MAMs and autophagy in cancer cells and addresses how these networks might be manipulated to improve anticancer therapeutics. PMID- 26284196 TI - The Art of Intraoperative Glioma Identification. AB - A major dilemma in brain-tumor surgery is the identification of tumor boundaries to maximize tumor excision and minimize postoperative neurological damage. Gliomas, especially low-grade tumors, and normal brain have a similar color and texture, which poses a challenge to the neurosurgeon. Advances in glioma resection techniques combine the experience of the neurosurgeon and various advanced technologies. Intraoperative methods to delineate gliomas from normal tissue consist of (1) image-based navigation, (2) intraoperative sampling, (3) electrophysiological monitoring, and (4) enhanced visual tumor demarcation. The advantages and disadvantages of each technique are discussed. A combination of these methods is becoming widely accepted in routine glioma surgery. Gross total resection in conjunction with radiation, chemotherapy, or immune/gene therapy may increase the rates of cure in this devastating disease. PMID- 26284194 TI - Recapitulating the Tumor Ecosystem Along the Metastatic Cascade Using 3D Culture Models. AB - Advances in cancer research have shown that a tumor can be likened to a foreign species that disrupts delicately balanced ecological interactions, compromising the survival of normal tissue ecosystems. In efforts to mitigate tumor expansion and metastasis, experimental approaches from ecology are becoming more frequently and successfully applied by researchers from diverse disciplines to reverse engineer and re-engineer biological systems in order to normalize the tumor ecosystem. We present a review on the use of 3D biomimetic platforms to recapitulate biotic and abiotic components of the tumor ecosystem, in efforts to delineate the underlying mechanisms that drive evolution of tumor heterogeneity, tumor dissemination, and acquisition of drug resistance. PMID- 26284199 TI - Pelvic Floor Muscle Exercise for Paediatric Functional Constipation. AB - INTRODUCTION: Functional constipation (FC) is one of the most common gastrointestinal problems among children. This study was designed to investigate the effectiveness of pelvic floor muscle exercise on treatment of FC. MATERIALS AND METHODS: In this study which was conducted in Children's Medical Center, children with a diagnosis of FC (aged 4-18 y) who did not respond to medical treatment, performed sessions of pelvic floor muscle exercise at home twice a day for 8 wk. Frequency of defecation, overall improvement of constipation, stool withholding, painful defecation and stool consistency were measured at the final week of the intervention compared to baseline. RESULTS: Forty children (16 males, 24 females mean age 5.6+/-1.03 y) completed the 8-wk exercise program. Subjective overall improvement of the symptoms was present in 36 patients (90%). The changes in stool frequency, stool diameter and consistency were statistically significant. However, there were no statistically significant differences in the stool withholding, fecal impaction, fecal incontinence and painful defecation. CONCLUSION: Pelvic floor muscle exercise is an effective non-pharmacologic treatment for Paediatric FC. PMID- 26284198 TI - A Method for the Immortalization of Newborn Mouse Skin Keratinocytes. AB - Isolation and culture of mouse primary epidermal keratinocytes is a common technique that allows for easy genetic and environmental manipulation. However, due to their limited lifespan in culture, experiments utilizing primary keratinocytes require large numbers of animals, and are time consuming and expensive. To avoid these issues, we developed a method for the immortalization of primary mouse epidermal keratinocytes. Upon isolation of newborn epidermal keratinocytes according to established methods, the cells were cultured long-term in keratinocyte growth factor-containing medium. The cells senesced within a few weeks and eventually, small, slowly growing colonies emerged. After they regained confluency, the cells were passaged and slowly refilled the dish. With several rounds of subculture, the cells adapted to culture conditions, were easily subcultured, maintained normal morphology, and were apparently immortal. The immortalized cells retained the ability to differentiate with increased calcium concentrations, and were maintained to high passage numbers while maintaining a relatively stable karyotype. Analysis of multiple immortalized cell lines as well as primary keratinocyte cultures revealed increased numbers of chromosomes, especially in the primary keratinocytes, and chromosomal aberrations in most of the immortalized cultures and in the primary keratinocytes. Orthotopic grafting of immortalized keratinocytes together with fibroblasts onto nude mouse hosts produced skin while v-ras(Ha) infection of the immortalized keratinocytes prior to grafting produced squamous cell carcinoma. In summary, this method of cell line generation allows for decreased use of animals, reduces the expense and time involved in research, and provides a useful model for cutaneous keratinocyte experimentation. PMID- 26284197 TI - Targeting Epigenetic Processes in Photodynamic Therapy-Induced Anticancer Immunity. AB - Photodynamic therapy (PDT) of cancer is an approved therapeutic procedure that generates oxidative stress leading to cell death of tumor and stromal cells. Cell death resulting from oxidative damage to intracellular components leads to the release of damage-associated molecular patterns (DAMPs) that trigger robust inflammatory response and creates local conditions for effective sampling of tumor-associated antigens (TAA) by antigen-presenting cells. The latter can trigger development of TAA-specific adaptive immune response. However, due to a number of mechanisms, including epigenetic regulation of TAA expression, tumor cells evade immune recognition. Therefore, numerous approaches are being developed to combine PDT with immunotherapies to allow development of systemic immunity. In this review, we describe immunoregulatory mechanisms of epigenetic treatments that were shown to restore the expression of epigenetically silenced or down-regulated major histocompatibility complex molecules as well as TAA. We also discuss the results of our recent studies showing that epigenetic treatments based on administration of methyltransferase inhibitors in combination with PDT can release effective mechanisms leading to development of antitumor immunity and potentiated antitumor effects. PMID- 26284200 TI - T-cell Lymphoblastic Lymphoma in the Maxilla and Mandible of a Child: A Rare Case Report. AB - T-cell lymphoblastic lymphomas (T-LBL), defined as neoplasms of immature T cells, are the most common paediatric T-cell lymphoma. These account for approximately 90% of all lymphoblastic lymphomas. The primary manifestation of T-LBL rarely occurs in the oral cavity. In this case report, we describe a case of primary T LBL affecting the maxilla and mandible of a 10-year-old male patient. This is the first case of T-LBL reported in this region. We emphasize that early diagnosis of aggressive lesions in the maxilla or mandible is one of the responsibilities of oral physicians, who can help patients to overcome the many challenges of malignant diseases. PMID- 26284201 TI - What Is Fitness Training? Definitions and Implications: A Systematic Review Article. AB - BACKGROUND: This review based upon studies searched from the major scientific libraries has the objective of clarifying what is fitness training in modern days, the implications that it has on health in both youth and elderly and finally discuss fitness training practical implications. METHODS: The PRISMA statement was partially adopted and a number of 92 items were selected, according to the inclusion criteria. Results were discussed in 4 main sections: 1. Children and adolescents fitness levels; 2. Fitness training in the elderly; 3. Pathology prevention through fitness training; 4. Training through Fitness activities. RESULTS: This review pointed out the fact that nowadays there is a large variety of fitness activities available within gyms and fitness centers. Even though they significantly differ with each other, the common aim they have is the wellbeing of the people through the improvement of the physical fitness components and the psychological balance. CONCLUSION: Fitness instructors' recommendations should be followed in gym context and should be contingent upon an individual's objectives, physical capacity, physical characteristics and experience. PMID- 26284203 TI - Household Solid Fuel Use and Cardiovascular Disease in Rural Areas in Shanxi, China. AB - BACKGROUND: More than 80 percent of the China's population is located in the rural areas, 95 percent of which use coal, wood etc for cooking and heating. Limited by data availability, the association between household solid fuels and cardiovascular diseases (CVDs) in China's rural areas is ignored in prior studies. METHODS: This cross sectional study was conducted from 2010-2012 and carried out on rural population aging 20-80 yr, comprised of 13877 participants from eighteen villages. Self-report questionnaire data were collected. Each outcome represents whether the participant has a kind of CVDs or not and it is reported in participants' questionnaire. Then the collected data is analyzed by logistic regression models with odds ratios (OR) and 95 percent confidence interval. RESULTS: After adjusting for potential confounders, the use of household solid fuels was significantly associated with an increased risk for hypertension (OR 1.751), CHD (OR 2.251), stroke (OR 1.642), diabetes (OR 1.975) and dyslipidemia (OR 1.185). Residents with the highest tertile of the duration of household solid fuel exposure had an increased odd of hypertension (OR 1.651), stroke (OR 1.812), diabetes (OR 2.891) and dyslipidemia (OR 1.756) compared with those in the lowest tertile of the duration of solid fuel exposure. CONCLUSION: Indoor pollution exposure from household solid fuels combustion may be a positive risk factor for CVDs in the perspectives of China's rural population. Our findings should be corroborated in longitudinal studies. PMID- 26284202 TI - Intercellular Adhesion Molecule-1 (ICAM-1) Polymorphisms and Cancer Risk: A Meta Analysis. AB - BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) Lys469Glu (K469E) polymorphism and Gly 241Arg (G241R) polymorphism might play important roles in cancer development and progression. However, the results of previous studies are inconsistent. The aim of this study was to evaluate the association between ICAM 1 K469E and G241R polymorphisms and the risk of cancer by meta-analysis. METHODS: A comprehensive literature search (last search updated in November 2013) was conducted to identify case-control studies that investigated the association between ICAM-1 K469E and G241R polymorphisms and cancer risk. RESULTS: A total of 18 case-control studies for ICAM-1 polymorphisms were included in the meta analysis, including 4,844 cancer cases and 5,618 healthy controls. For K469E polymorphism, no significant association was found between K469E polymorphism and cancer risk. However, subgroup analysis by ethnicity revealed one genetic comparison (GG vs. AA) presented the relationship with cancer risk in Asian subgroup, and two genetic models (GG+GA vs. AA and GA vs. AA) in European subgroup, respectively. For G241R polymorphism, G241R polymorphism was significantly association with cancer risk in overall analysis. The subgroup analysis by ethnicity showed that G241R polymorphism was significantly associated with cancer risk in European subgroup. CONCLUSION: ICAM-1 G241R polymorphism might be associated with cancer risk, especially in European populations, but the results doesn't support ICAM-1 K469E polymorphism as a risk factor for cancer. PMID- 26284205 TI - Mother's Happiness with Cognitive - Executive Functions and Facial Emotional Recognition in School Children with Down Syndrome. AB - BACKGROUND: According to the mother's key roles in bringing up emotional and cognitive abilities of mentally retarded children and respect to positive psychology in recent decades, this research is administered to assess the relation between mother's happiness level with cognitive- executive functions (i.e. attention, working memory, inhibition and planning) and facial emotional recognition ability as two factors in learning and adjustment skills in mentally retarded children with Down syndrome. METHODS: This study was an applied research and data were analyzed by Pearson correlation procedure. Population is included all school children with Down syndrome (9-12 yr) that come from Tehran, Iran. Overall, 30 children were selected as an in access sample. After selection and agreement of parents, the Wechsler Intelligence Scale for Children-Revised (WISC R) was performed to determine the student's IQ, and then mothers were invited to fill out the Oxford Happiness Inventory (OHI). Cognitive-executive functions were evaluated by tests as followed: Continues Performance Test (CPT), N-Back, Stroop test (day and night version) and Tower of London. Ekman emotion facial expression test was also accomplished for assessing facial emotional recognition in children with Down syndrome, individually. RESULTS: Mother's happiness level had a positive relation with cognitive-executive functions (attention, working memory, inhibition and planning) and facial emotional recognition in her children with Down syndrome, significantly. CONCLUSION: Parents' happiness (especially mothers) is a powerful predictor for cognitive and emotional abilities of their children. PMID- 26284204 TI - Dietary Intake in Body Mass Index Differences in Community-Based Japanese Patients with Schizophrenia. AB - BACKGROUND: Patients with schizophrenia reportedly have a high prevalence of obesity. One of the reasons is a poor choice of diet. The goal of this study was to clarify characteristics of the dietary intake across the strata of the body mass index (BMI) and to compare the general population and patients with schizophrenia in Japan. METHODS: This is a cross-sectional study of 51 patients with schizophrenia residing in rural areas in 2011. Anthropometric indices (of height, weight, body mass index) were measured at the commencement of the survey. Intakes of energy, protein, fat, carbohydrate, calcium, phosphorus, vitamins, total fiber, and salt were noted through a 3-day dietary recording. The nutrient intake was estimated using Excel add-in software (Excel Eiyou-kun Ver. 6.0, Kenpakusha Co., Ltd.). Patients were divided into two groups: those with a BMI >=25 kg/m(2) and with a BMI <25 kg/m(2), and the differences in their nutrition intake were analyzed. To compare these patients with the general population, the results of the National Health and Nutrition Survey, 2010 (NHNS) were used (the NHNS group). For statistical analysis, an unpaired t-test was performed with P < 0.05. RESULTS: Patients with a BMI >=25 kg/m(2) had the higher intakes than those with a BMI <25 kg/m(2) of energy, fat and phosphorus and salt. Patients with schizophrenia showed higher intakes of energy, carbohydrate, fat, calcium, phosphorus and salt than the NHNS group. CONCLUSION: The characteristics of the dietary intake in patients with schizophrenia were suggested the food constitution that is likely to increase the body weight. PMID- 26284206 TI - Seroepidemiological Study of Toxoplasmosis in Women Referred to Arak Marriage Consulting Center during 2012-2013. AB - BACKGROUND: Toxoplasmosis is a zoonotic and usually asymptomatic infection. This study was carried out to investigate the seroepidemiology of Toxoplasma infection in women referred to Arak Marriage Consulting Center during 2012-2013. METHODS: In this cross-sectional study, serum samples were collected from 400 women referred to Marriage Consulting Center in Arak City, Markazi Province, central Iran during 2012-2013. Anti-Toxoplasma IgG and IgM antibodies were measured by ELISA using homemade antigen. Results were analyzed by SPSS 18 and the correlation between toxoplasmosis and some affecting factors were estimated. RESULTS: Overall, 97 cases (24.3%) had IgG antibodies against T. gondii and 19 cases (4.8%) were positive for IgM antibodies. A significant correlation was seen between T. gondii infection with clinical symptoms, keeping cat as pet animal, education and handling or eating raw or undercooked meat (P < 0.05). CONCLUSION: The prevalence of (24.3%) for Toxoplasma infection was seen in Arak City. It seems that keeping cat as pet and consumption of undercooked liver and uncooked hamburger are the most important transmission routes for the infection in this city. Since the majority of women are Toxoplasma sero-negative (75.7%) in Arak City, using serological tests and health education prior to marriage or during pregnancy is recommended. PMID- 26284207 TI - Community Eagerness and Participation for Supporting Eliminate Malaria. AB - BACKGROUND: This study was undertaken to identify key elements for obtaining community interest and motivate them to support eliminate malaria in the places that malaria is no longer a perceived threat. METHODS: Sequential explanatory mixed methods research design used to provide more comprehensive evidence research. A questionnaire was developed after reviewing the literature relating to community participation for malaria elimination and used to collect data from three native people, Iranian migrant and foreign immigrant groups. The variables included access to educational facilities, services, social support, social supporters, trust, and supportive norms were assessed. We also employed an ethnographic design involving: observation participant (PO), Key informant interviews (KIIs), and focus group discussions (FGDs). RESULTS: The results revealed that predisposing, enabling and reinforcing factors had association with community involvement. Less than 50% of total respondents reported have access to educational sessions, most of them were unaware of available and affordable services. Differences views regarding to social support influence have been found among respondents. Although patterns of social interactions were almost similar in all residents, frequencies of interactions were varied. Three thematic areas emerged including perceptions on involvement, potential barriers, and focus areas for the training community members. CONCLUSION: These findings indicate needs for greater understanding about how to strengthen community involvement with emphasize for community capacity building. This research has benefit to national and regional efforts to increase community involvement as a source for effective actions on malaria elimination. PMID- 26284208 TI - Personal Exposure to Polycyclic Aromatic Hydrocarbons in Newsagents in Tehran, Iran. AB - BACKGROUND: Vehicle exhaust is a major source of exposure to Polycyclic Aromatic Hydrocarbons (PAHs) found in the urban atmosphere. Newsagents usually work close to heavy traffic flow. The purpose of this study was to assess the breathing zone exposure of newsagents to PAHs found in the urban atmosphere of Tehran City during summer and autumn seasons and comparing the levels of exposure in both seasons. METHODS: Fifteen non-smoking newsagents were randomly selected from north, south, east, west, and center of Tehran. Particle and gas phases PAHs were collected on polytetrafluoroethylene (PTFE) filter and XAD-2 adsorbent. Gas chromatography-mass spectrometry (GC/MS) was used to determine PAHs concentrations in newsagent's breathing zone samples. RESULTS: The highest and lowest values of exposures during summer and autumn in all sampling stations were recorded for benzo[a]anthracene and benzo[ghi]perylene, respectively. Mann Whitney test results showed that seasonal variation had significant influence on concentrations of all studied PAHs (P= 0.001) except benzo[ghi]perylene (P= 0.089). An increase in concentrations of PAHs was observed in autumn. CONCLUSION: The workers of the newsstands in the south area of Tehran City were experiencing higher levels of exposures to PAHs. Newsagents' breathing zone exposures to PAHs during the cold period were two to three folds higher than those during the warm period were. The levels of exposures in all sampling stations were below the OSHA and NIOSH's recommended exposure limits. PMID- 26284209 TI - Association between Glutathione S-Transferase GSTM1-T1 and P1 Polymorphisms with Metabolic Syndrome in Zoroastrians in Yazd, Iran. AB - BACKGROUND: The aim of this study was to assess the possible association between genetic polymorphisms of the glutathione S-transferase (GST) gene family and the risk of the development of metabolic syndrome (MS) in Zoroastrian females in Yazd, Iran. METHODS: In this case-control study, GSTM1, T1, and P1 polymorphisms were genotyped in 51 randomly selected MS patients and 50 randomly selected healthy controls on February 2014 among Zoroastrian females whose ages ranged from 40 to 70 yr. DNA was extracted from peripheral blood. Data were analyzed with SPSS version 17. RESULTS: We observed a significant association of GSTP1-I/V (Isoleucine/Valine) allele and GSTP1-V/V (Valine / Valine) allele with MS (P = 0.047 and P = 0.044, respectively). The combined analysis of the two genotypes, the present genotype of GSTT1, I/V and V/V alleles of GSTP1 genotype demonstrated a decrease in the risk of acquiring MS (OR = 0.246, P = 0.031). The null genotype of GSTM1, I/V, and V/V alleles of the GSTP1 genotype showed a lower risk in double combinations (OR = 0.15, P = 0.028 and OR = 0.13, P = 0.013, respectively). The combinations of the GSTM1 null genotypes and GSTT1 present genotypes and the GSTP1 I/V and V/V alleles together were associated with decreased risk of having MS in triple combinations (OR = 0.071, P = 0.039 and OR = 0.065, P = 0.022, respectively). CONCLUSION: GSTP1-I/V and V/V alleles, alone or in association with GSTM1 null and GSTT1 present genotypes, are related with decreased susceptibility to the development of MS in Zoroastrian females. PMID- 26284210 TI - Identify Survival Predictors of the First Kidney Transplantation: A Retrospective Cohort Study. AB - BACKGROUND: The first kidney transplant survival is very important. We know that short-term survival of kidney transplantation is improved over the past two decades in Iran; however, no information is available on long-term survival and predictors. This study explored factors influencing long-term renal transplant survival at northwest of Iran. METHODS: In this single-center, study, survival rates and half-life of 201 the first kidney transplants between 1999 and 2008 were measured by a historical-cohort study in Imam Khomeini Hospital in Urmia, Iran. The log-rank test and Cox-regression model were used to compare survival curves and determine factor affecting graft survival time, respectively. RESULTS: First graft survival from one, five, and 10 years was 96%, 89%, and 46%, respectively. Mean+/-se and median+/-se of first graft survival time was 3061+/ 105.01 day (95% CI: 2855.47-3267.11 day) and 3411+/-282.1 day (95%CI: 2858.08 3963.92), respectively. Predictors of first graft rejection were recipient age (P=0.001), LDL cholesterol (P=0.008), immunosuppressive drugs (P=0.047), serum creatinine three and six months (P=0.042 and 0.001, respectively) and related donor family (P=0.037). CONCLUSION: Patients with first graft transplantation had a moderate long-term survival. The study showed that small age at transplant, low LDL cholesterol before transplant, and relative to donor, could be decrease the risk graft loss. PMID- 26284211 TI - Serum 25-Hydroxyvitamin D in Patients with Major Depressive Disorder. AB - BACKGROUND: We investigated the association between serum 25(OH) D levels and depressive symptoms in patients with major depressive disorder (MDD). METHODS: Eighty-five adults, 44 drug free patients with MDD and 41 apparently healthy controls, participated in the study. The Hamilton Depression Rating Scale was used to assess severity of major depression. Mental health of the controls was assessed according to DSM-IV criteria. Stress level of the participants was assessed by the Holmes and Rahe stress scale. Serum 25(OH) D levels was measured by immunochemiluminescence assay. Vitamin D deficiency was defined as a serum 25(OH) D concentration of lower than 20 ng/ml. RESULTS: Depressed patients had the higher levels of stress. There was a positive correlation between stress level and disease severity (r= 0.32, P= 0.03). In total participants, mean percentage of vitamin D deficiency was 77.6% with 75% in patients and 80.5% in the healthy subjects. There were no differences between the two groups in serum 25(OH) D levels and percentage of subjects with the vitamin deficiency. A negative correlation was observed between disease severity and serum 25(OH) D level of patients with depression episodes < 2 y (r= -0.38, P = 0.08) and winter samples (samples collected and measured from December to march, r= -0.62, P = 0.004). CONCLUSION: Serum 25(OH) D levels were not associated with depression. However, the inverse relationship between levels of vitamin D and depressive symptoms in current depression episodes and in sun-deprived season warrants further investigation. PMID- 26284212 TI - Dioctophyme renale in Vulpes vulpes from the Caspian Sea littoral of Iran. AB - During a long term of road survey for detection of the zoonotic helminthes in carnivores, a male Vulpes vulpes was naturally found infected by Dioctophyme renale in Caspian Sea littoral in Iran. Since the parasite transmission usually occurs through consumption of fish and other accidental food items, investigation of the worm amongst fish-eating animals in the areas with potential circulation of the helminth life cycle, has been regarded as a public health importance so far. Concerning the rout of parasite transmission to humans, different epidemiological aspects should be studied in the country. Present paper describes a destructive lesion of the kidney in the fox due to D. renale after almost a decade of monitoring for the parasite reservoirs in the region. PMID- 26284213 TI - Effect of Three-year Multi-Component Exercise Training on Bone Mineral Density and Content in a Postmenopausal Woman with Osteoporosis: A Case Report. AB - The purpose of the present study was to examine the effect of 3-years of moderate multi-component exercise training on bone mineral density and bone mineral content in a female subject with osteoporosis. A 57-year-old postmenopausal woman, a known case of osteoporosis following an accident, participated in this study. Bone mineral density and bone mineral content was measured in the femoral neck area and the lumbar spine by dual energy X-ray absorptiometry. The measurements lasted four years, first year without any exercise training and three succeeding years with exercise intervention. After three years of exercise training, bone mineral density and bone mineral content were improved in both regions, despite the increase in age and decrease in weight. This case highlights the importance of exercise training in maintaining and increasing bone mineral density and bone mineral content of the spine and hip in post-menopausal women. Considering its positive effects, regular and lifelong exercise training must be incorporated into peoples' life due to the chronic nature of bone loss in aging process. PMID- 26284214 TI - Comparison of Physical Activity Level among Childhood Cancer Survivors in Korea. PMID- 26284215 TI - Nano Aeon: Looming Phase in Medical Dentistry-Prospects for the Future. PMID- 26284216 TI - Relationship between Doctors' Prescribing Behavior and Pharmaceutical Promotional Tools: A Pakistani Case. PMID- 26284217 TI - Knowledge and Attitude toward Tuberculosis among Tuberculosis Patients Seeking Help in Diagnostic and Treatment Centers, Kabul Province in Afghanistan. PMID- 26284218 TI - Comments on "Use of Malondialdehyde as a Biomarker for Assesing Oxidative Stress in Different Disease Pathologies: A Review". PMID- 26284219 TI - Afraid of the Dark; Raising Awareness of Societies Each Year during World Glaucoma Week. PMID- 26284220 TI - Acceptance and Commitment Therapy (ACT) For Generalized Anxiety Disorder. PMID- 26284221 TI - Emergency Medicine Residency Program in Iran: Practical Options to Achieve Better Performance. PMID- 26284222 TI - Genetic Variation Impacts in Patients with Major Beta-Thalassemia. PMID- 26284223 TI - Physical Exercises and Motor Skills in Autistic Children. PMID- 26284224 TI - The Myth of Penicillin/Dexamethasone and Its Costs to the Health Care System of Iran. PMID- 26284225 TI - Comparing the effect of oral and vaginal isosorbide dinitrate in pre-induction cervical ripening in term pregnancy: A controlled clinical trial. AB - BACKGROUND: Cervical ripening for labor induction is one of the most important issues in midwifery. Isosorbide dinitrate (ISDN) is one of the most important choices that have been proposed for cervical ripening, but still there are controversies regarding its prescription. The present study aimed to evaluate the effects of vaginal and oral ISDN compared to the control group for pre-induction cervical ripening. MATERIALS AND METHODS: In this non-blinded clinical trial, 149 nulliparous women with term or prolonged pregnancy were randomly selected and divided into three groups by block randomization. The intervention group included vaginal (50 subjects, 40 mg) and oral (49 subjects, 20 mg) ISDN groups. The third group was the control group (50 subjects) which did not receive any medication. The amount of ripening was given by Bishop score evaluated before taking medication and 24 h after taking it. RESULTS: After 24 h, Bishop score in vaginal ISDN group significantly increased compared to the oral ISDN and control groups (P < 0.001 for both). Although the increase in Bishop score was lower in the oral ISDN group than in the vaginal group, it had a statistically significant increase in comparison to the control group (P = 0.001). All the three groups were matched regarding pregnancy termination and cesarean causes, and there was no statistically significant difference among the three groups (P > 0.05). CONCLUSION: Prescribing vaginal ISDN for cervical ripening was effective, and it can be used with confidence. PMID- 26284227 TI - Blunted Heart Rate Response as a Potential Endophenotype of Substance Use Disorders: Evidence from High-Risk Youth. AB - BACKGROUND: Children of parents with a substance use disorder (CPSUD) are at increased risk for developing problematic substance use later in life. Endophenotypes may help to clarify the mechanism behind this increased risk. However, substance use and externalizing symptoms may confound the relation between dysregulated physiological stress responding and familial risk for substance use disorders (SUDs). METHODS: We examined whether heart rate (HR) responses differed between CPSUDs and controls. Participants (aged 11-20 years) were CPSUDs (N = 75) and controls (N = 363), semi-matched on the basis of sex, socioeconomic status, and ethnicity. HR was measured continuously during a psychosocial stress procedure. Substance use and externalizing symptoms were self reported and mother-reported, respectively. RESULTS: A piecewise, mixed-effects model was fit for HR across the stress procedure, with fixed effects for HR reactivity and HR recovery. CPSUDs showed a blunted HR recovery. CPSUDs reported drinking more frequently, were more likely to use tobacco daily, were more likely to report ever use of cannabis and used cannabis more frequently, and exhibited more externalizing symptoms. These variables did not confound the relation between familial risk for SUDs and a blunted HR recovery. CONCLUSION: Our findings suggest dysregulated autonomic nervous system (ANS) responding in CPSUDs and contribute to the accumulating evidence for ANS dysregulation as a potential endophenotype for SUDs. PMID- 26284229 TI - The Implications of Metabotypes for Rationalizing Therapeutics in Infants and Children. PMID- 26284228 TI - Clinical Impact and Cost-Effectiveness of Whole Exome Sequencing as a Diagnostic Tool: A Pediatric Center's Experience. AB - BACKGROUND: There are limited reports of the use of whole exome sequencing (WES) as a clinical diagnostic tool. Moreover, there are no reports addressing the cost burden associated with genetic tests performed prior to WES. OBJECTIVE: We demonstrate the performance characteristics of WES in a pediatric setting by describing our patient cohort, calculating the diagnostic yield, and detailing the patients for whom clinical management was altered. Moreover, we examined the potential cost-effectiveness of WES by examining the cost burden of diagnostic workups. METHODS: To determine the clinical utility of our hospital's clinical WES, we performed a retrospective review of the first 40 cases. We utilized dual bioinformatics analyses pipelines based on commercially available software and in house tools. RESULTS: Of the first 40 clinical cases, we identified genetic defects in 12 (30%) patients, of which 47% of the mutations were previously unreported in the literature. Among the 12 patients with positive findings, seven have autosomal dominant disease and five have autosomal recessive disease. Ninety percent of the cohort opted to receive secondary findings and of those, secondary medical actionable results were returned in three cases. Among these positive cases, there are a number of novel mutations that are being reported here. The diagnostic workup included a significant number of genetic tests with microarray and single-gene sequencing being the most popular tests. Significantly, genetic diagnosis from WES led to altered patient medical management in positive cases. CONCLUSION: We demonstrate the clinical utility of WES by establishing the clinical diagnostic rate and its impact on medical management in a large pediatric center. The cost-effectiveness of WES was demonstrated by ending the diagnostic odyssey in positive cases. Also, in some cases it may be most cost effective to directly perform WES. WES provides a unique glimpse into the complexity of genetic disorders. PMID- 26284226 TI - Decision-Making for Surgery in the Management of Patients with Univentricular Heart. AB - A series of technical refinements over the past 30 years, in combination with advances in perioperative management, have resulted in dramatic improvements in the survival of patients with univentricular heart. While the goal of single ventricle palliation remains unchanged - normalization of the pressure and volume loads on the systemic ventricle, the strategies to achieve that goal have become more diverse. Optimal palliation relies on a thorough understanding of the changing physiology over the first years of life and the risks and consequences of each palliative strategy. This review describes how to optimize surgical decision-making in univentricular patients based on a current understanding of anatomy, physiology, and surgical palliation. PMID- 26284230 TI - Discovering Multi-Scale Co-Occurrence Patterns of Asthma and Influenza with Oak Ridge Bio-Surveillance Toolkit. AB - We describe a data-driven unsupervised machine learning approach to extract geo temporal co-occurrence patterns of asthma and the flu from large-scale electronic healthcare reimbursement claims (eHRC) datasets. Specifically, we examine the eHRC data from 2009 to 2010 pandemic H1N1 influenza season and analyze whether different geographic regions within the United States (US) showed an increase in co-occurrence patterns of the flu and asthma. Our analyses reveal that the temporal patterns extracted from the eHRC data show a distinct lag time between the peak incidence of the asthma and the flu. While the increased occurrence of asthma contributed to increased flu incidence during the pandemic, this co occurrence is predominant for female patients. The geo-temporal patterns reveal that the co-occurrence of the flu and asthma are typically concentrated within the south-east US. Further, in agreement with previous studies, large urban areas (such as New York, Miami, and Los Angeles) exhibit co-occurrence patterns that suggest a peak incidence of asthma and flu significantly early in the spring and winter seasons. Together, our data-analytic approach, integrated within the Oak Ridge Bio-surveillance Toolkit platform, demonstrates how eHRC data can provide novel insights into co-occurring disease patterns. PMID- 26284231 TI - More than Just a Meal: Breakfast Club Attendance and Children's Social Relationships. AB - The health benefits of school food have been widely promoted in recent years while the social opportunities that surround eating occasions at school have received little attention. Breakfast clubs (BCs), which take place at the start of the school day, offer a unique opportunity for children to consume a breakfast meal on their school premises in the company of their peers. Alternatively, after school clubs (ASCs), which take place on school premises at the end of the school day, whilst also providing children with social opportunities tend to focus on sports engagement and skill development. The aim of the current paper is to investigate whether attendance at BCs and ASCs has an impact on children's friendship quality and experiences of peer victimization. BC attendees, ASC attendees, and non-attendees completed the Friendship Qualities Scale and the Multidimensional Peer Victimization Scale (MPVS) at two time points. Time-1 data were collected 2 months after the introduction of school clubs. Time-2 data were then collected on the same measures again 6 months later. Results of the analyses of Time-1 data showed no significant differences between groups on any of the measures at Time-1. However, at Time-2, BC attendees showed improved levels of friendship quality compared to the other two groups. Moreover, analysis of the MPVS data at Time-2 showed that children who attended BC or ASC experienced a decline in victimization across time. The current findings suggest that BC attendance facilitates the quality of children's relationships with their best friend over time. Additionally, attendance at a breakfast or ASC was associated with a reduction in victimization over time. The results have implications for utilization of breakfast and ASCs to aid children's social relationships in school over time. PMID- 26284232 TI - Nutrition Leadership Development: Capacity-Building Initiatives in Iran and the Middle-East Region Since 2009. AB - Personal and organizational performance is determined by commitment and both technical and general competencies, including leadership skills. Academia, however, mainly targets technical aspects in its curricular programs. On the other hand, the inter-disciplinary and multi-sector nature of Nutrition necessitates high levels of collaboration between stakeholders. Leadership development is therefore required in Nutrition. This paper describes the endeavor made in Iran and the Middle-East region, aiming at building leadership capacity among nutrition professionals. The empowered human resource is expected to facilitate nutrition security at the national and regional levels. Since 2007, the development process of the initiative has begun through research, bench marking, and consultation. The "learning organizations," "leadership from inside out," and "transformational leadership" frameworks have been employed as underpinning theories. Main topics have been self-awareness, effective communication, shared visioning, trust building, creativity, and motivating. Outbound team-building activities and coaching have also been included. The first workshop of the Iranian Food and Nutrition Leadership Program was held in 2009 in Tehran. The experience expanded to the region as the Middle-East Nutrition Leadership Program (MENLP). The Ph.D. Nutrition programs (at four leading Universities) and Iranian Nutrition Society have been taken as other opportunity windows to develop leadership competencies. Biannual Iranian nutrition congresses have been used as the main media for advocacy purposes. High-satisfaction rates obtained following each training activity. In short, the initiative on "nutrition leadership development" has received growing investment and positive feedback in Iran. Continuous improvement of the initiative, establishment of active alumni networks, building MENLP regional platform, and integrating a monitoring and evaluation system are required to increase the investment returns. PMID- 26284234 TI - Climate Regimes, El Nino-Southern Oscillation, and Meningococcal Meningitis Epidemics. AB - Meningococcal meningitis is a major public health problem that kills thousands annually in Africa, Europe, North, and South America. Occurrence is, however, highest during the dry seasons in Sahel Africa. Interannual changes in precipitation correlate with interannual changes in El Nino-Southern Oscillation (ENSO), while interdecadal changes in precipitation correlate with Pacific Decadal Oscillation (PDO). The objective of the study was to determine if there is spectral coherence of seasonal, interannual, and interdecadal changes in occurrence of meningococcal meningitis in Sahel, Central, and East Africa with interannual and interdecadal changes of PDO and ENSO. Time series were fitted to occurrence of meningococcal meningitis in Sahel, Central, and East Africa, to indices of precipitation anomalies in the Sahel, and to indices of ENSO and PDO anomalies. Morlet wavelet was used to transform the time series to frequency-time domain. Wavelet spectra and coherence analyses were performed. Occurrence of meningococcal meningitis showed seasonal, interannual, and interdecadal changes. The magnitude of occurrence was higher during warm climate regime, and strong El Ninos. Spectra coherence of interannual and interdecadal changes of ENSO and PDO with occurrence of meningococcal meningitis in Sahel, Central, and East Africa were significant at p < 0.0001. Precipitation in Sahel was low during warm climate regimes. Spectra coherence of changes in precipitation in Sahel with ENSO was significant at p < 0.0001. ENSO and PDO are determinants of the seasonal, interannual, and interdecadal changes in occurrence of meningococcal meningitis. Public health management of epidemics of meningococcal meningitis should include forecast models of changes in ENSO to predict periods of low precipitation, which initiate occurrence. PMID- 26284233 TI - Developing National Cancer Registration in Developing Countries - Case Study of the Nigerian National System of Cancer Registries. AB - The epidemiological transition in sub-Saharan Africa (SSA) has given rise to a concomitant increase in the incidence of non-communicable diseases including cancers. Worldwide, cancer registries have been shown to be critical for the determination of cancer burden, conduct of research, and in the planning and implementation of cancer control measures. Cancer registration though vital is often neglected in SSA owing to competing demands for resources for healthcare. We report the implementation of a system for representative nation-wide cancer registration in Nigeria - the Nigerian National System of Cancer Registries (NSCR). The NSCR coordinates the activities of cancer registries in Nigeria, strengthens existing registries, establishes new registries, complies and analyses data, and makes these freely available to researchers and policy makers. We highlight the key challenges encountered in implementing this strategy and how they were overcome. This report serves as a guide for other low- and middle income countries (LMIC) wishing to expand cancer registration coverage in their countries and highlights the training, mentoring, scientific and logistic support, and advocacy that are crucial to sustaining cancer registration programs in LMIC. PMID- 26284235 TI - An ameliorative protocol for the quantification of purine 5',8-cyclo-2' deoxynucleosides in oxidized DNA. AB - 5',8-Cyclo-2'-deoxyadenosine (cdA) and 5',8-cyclo-2'-deoxyguanosine (cdG) are lesions resulting from hydroxyl radical (HO (.) ) attack on the 5'H of the nucleoside sugar moiety and exist in both 5'R and 5'S diastereomeric forms. Increased levels of cdA and cdG are linked to Nucleotide Excision Repair (NER) mechanism deficiency and mutagenesis. Discrepancies in the damage measurements reported over recent years indicated the weakness of the actual protocols, in particular for ensuring the quantitative release of these lesions from the DNA sample and the appropriate method for their analysis. Herein we report the detailed revision leading to a cost-effective and efficient protocol for the DNA damage measurement, consisting of the nuclease benzonase and nuclease P1 enzymatic combination for DNA digestion followed by liquid chromatography isotope dilution tandem mass spectrometry analysis. PMID- 26284236 TI - Network Neurodegeneration in Alzheimer's Disease via MRI Based Shape Diffeomorphometry and High-Field Atlasing. AB - This paper examines MRI analysis of neurodegeneration in Alzheimer's Disease (AD) in a network of structures within the medial temporal lobe using diffeomorphometry methods coupled with high-field atlasing in which the entorhinal cortex is partitioned into eight subareas. The morphometry markers for three groups of subjects (controls, preclinical AD, and symptomatic AD) are indexed to template coordinates measured with respect to these eight subareas. The location and timing of changes are examined within the subareas as it pertains to the classic Braak and Braak staging by comparing the three groups. We demonstrate that the earliest preclinical changes in the population occur in the lateral most sulcal extent in the entorhinal cortex (alluded to as transentorhinal cortex by Braak and Braak), and then proceeds medially which is consistent with the Braak and Braak staging. We use high-field 11T atlasing to demonstrate that the network changes are occurring at the junctures of the substructures in this medial temporal lobe network. Temporal progression of the disease through the network is also examined via changepoint analysis, demonstrating earliest changes in entorhinal cortex. The differential expression of rate of atrophy with progression signaling the changepoint time across the network is demonstrated to be signaling in the intermediate caudal subarea of the entorhinal cortex, which has been noted to be proximal to the hippocampus. This coupled to the findings of the nearby basolateral involvement in amygdala demonstrates the selectivity of neurodegeneration in early AD. PMID- 26284237 TI - Bio-Hybrid Micro/Nanodevices Powered by Flagellar Motor: Challenges and Strategies. AB - Molecular motors, which are precision engineered by nature, offer exciting possibilities for bio-hybrid engineered systems. They could enable real applications ranging from micro/nano fluidics, to biosensing, to medical diagnoses. This review describes the fundamental biological insights and fascinating potentials of these remarkable sensing and actuation machines, in particular, bacterial flagellar motors, as well as their engineering perspectives with regard to applications in bio-engineered hybrid systems. PMID- 26284238 TI - Stability of Norwalk Virus Capsid Protein Interfaces Evaluated by in Silico Nanoindentation. AB - Norwalk virus causes severe gastroenteritis for which there is currently no specific anti-viral therapy. A stage of the infection process is uncoating of the protein capsid to expose the viral genome and allow for viral replication. A mechanical characterization of the Norwalk virus may provide important information relating to the mechanism of uncoating. The mechanical strength of the Norwalk virus has previously been investigated using atomic force microscopy (AFM) nanoindentation experiments. Those experiments cannot resolve specific molecular interactions, and therefore, we have employed a molecular modeling approach to gain insights into the potential uncoating mechanism of the Norwalk capsid. In this study, we perform simulated nanoindentation using a coarse grained structure-based model, which provides an estimate of the spring constant in good agreement with the experimentally determined value. We further analyze the fracture mechanisms and determine weak interfaces in the capsid structure, which are potential sites to inhibit uncoating by stabilization of these weak interfaces. We conclude by identifying potential target sites at the junction of a weak protein-protein interface. PMID- 26284239 TI - Variability in Wheelchair Propulsion: A New Window into an Old Problem. AB - Manual wheelchair users are at great risk for the development of upper extremity injury and pain. Any loss of upper limb function due to pain adversely impacts the independence and mobility of manual wheelchair users. There is growing theoretical and empirical evidence that fluctuations in movement (i.e., motor variability) are related to musculoskeletal pain. This perspectives paper discusses a local review on several investigations examining the association between variability in wheelchair propulsion and shoulder pain in manual wheelchair users. The experimental data reviewed highlights that the variability of wheelchair propulsion is impacted by shoulder pain in manual wheelchair users. We maintain that inclusion of these metrics in future research on wheelchair propulsion and upper limb pain may yield novel data. Several promising avenues for future research based on this collective work are discussed. PMID- 26284240 TI - PhenoMeter: A Metabolome Database Search Tool Using Statistical Similarity Matching of Metabolic Phenotypes for High-Confidence Detection of Functional Links. AB - This article describes PhenoMeter (PM), a new type of metabolomics database search that accepts metabolite response patterns as queries and searches the MetaPhen database of reference patterns for responses that are statistically significantly similar or inverse for the purposes of detecting functional links. To identify a similarity measure that would detect functional links as reliably as possible, we compared the performance of four statistics in correctly top matching metabolic phenotypes of Arabidopsis thaliana metabolism mutants affected in different steps of the photorespiration metabolic pathway to reference phenotypes of mutants affected in the same enzymes by independent mutations. The best performing statistic, the PM score, was a function of both Pearson correlation and Fisher's Exact Test of directional overlap. This statistic outperformed Pearson correlation, biweight midcorrelation and Fisher's Exact Test used alone. To demonstrate general applicability, we show that the PM reliably retrieved the most closely functionally linked response in the database when queried with responses to a wide variety of environmental and genetic perturbations. Attempts to match metabolic phenotypes between independent studies were met with varying success and possible reasons for this are discussed. Overall, our results suggest that integration of pattern-based search tools into metabolomics databases will aid functional annotation of newly recorded metabolic phenotypes analogously to the way sequence similarity search algorithms have aided the functional annotation of genes and proteins. PM is freely available at MetabolomeExpress (https://www.metabolome-express.org/phenometer.php). PMID- 26284241 TI - Overall Key Performance Indicator to Optimizing Operation of High-Pressure Homogenizers for a Reliable Quantification of Intracellular Components in Pichia pastoris. AB - The most commonly used cell disruption procedures may present lack of reproducibility, which introduces significant errors in the quantification of intracellular components. In this work, an approach consisting in the definition of an overall key performance indicator (KPI) was implemented for a lab scale high-pressure homogenizer (HPH) in order to determine the disruption settings that allow the reliable quantification of a wide sort of intracellular components. This innovative KPI was based on the combination of three independent reporting indicators: decrease of absorbance, release of total protein, and release of alkaline phosphatase activity. The yeast Pichia pastoris growing on methanol was selected as model microorganism due to it presents an important widening of the cell wall needing more severe methods and operating conditions than Escherichia coli and Saccharomyces cerevisiae. From the outcome of the reporting indicators, the cell disruption efficiency achieved using HPH was about fourfold higher than other lab standard cell disruption methodologies, such bead milling cell permeabilization. This approach was also applied to a pilot plant scale HPH validating the methodology in a scale-up of the disruption process. This innovative non-complex approach developed to evaluate the efficacy of a disruption procedure or equipment can be easily applied to optimize the most common disruption processes, in order to reach not only reliable quantification but also recovery of intracellular components from cell factories of interest. PMID- 26284243 TI - Progress and Challenges for Implementation of the Common Market for Eastern and Southern Africa Policy on Biotechnology and Biosafety. AB - In 2001, the Meeting of the COMESA Ministers of Agriculture raised concerns that proliferation of genetically modified organisms (GMOs) could impact significantly on trade and food security in the region. This triggered studies on a regional approach to biotechnology and biosafety policy in Eastern and Southern Africa. The studies and stakeholder consultations revealed that farm incomes would increase if they switched from conventional varieties of cotton and maize to genetically modified (GM) counterparts. Commercial risks associated with exports to GM sensitive destinations, e.g., EU were negligible. Intra-regional trade would be affected since exports of GM sensitive commodities, such as maize, cotton, and soya bean, mainly go to other African countries. These findings justified the need to consider a regional approach to biosafety and led to the drafting of a regional policy in 2009. The draft policies were discussed in regional and national workshops between 2010 and 2012 for wider ownership. The workshops involved key stakeholders including ministries of agriculture, trade, environment, national biosafety focal points, biosafety competent authorities, academia, seed traders, millers, the media, food relief agencies, the industry, civil society, competent authorities, and political opinion leaders. The COMESA Council of Ministers in February 2014 adopted the COMESA policy on biotechnology and biosafety that takes into account the sovereign right of each member state. Key provisions of the policy include recognition of the benefits and risks associated with GMOs; establishment of a regional-level biosafety risk-assessment system; national-level final decision, and capacity building assistance to member states. The policies are the first regional effort in Africa to develop a coordinated mechanism for handling biosafety issues related to GMO use. A regional approach to biotechnology and biosafety is expected to foster inter country cooperation through the sharing of knowledge, expertise, experiences, and resources. PMID- 26284242 TI - CO2 - Intrinsic Product, Essential Substrate, and Regulatory Trigger of Microbial and Mammalian Production Processes. AB - Carbon dioxide formation mirrors the final carbon oxidation steps of aerobic metabolism in microbial and mammalian cells. As a consequence, [Formula: see text] dissociation equilibria arise in fermenters by the growing culture. Anaplerotic reactions make use of the abundant [Formula: see text] levels for refueling citric acid cycle demands and for enabling oxaloacetate-derived products. At the same time, CO2 is released manifold in metabolic reactions via decarboxylation activity. The levels of extracellular [Formula: see text] depend on cellular activities and physical constraints such as hydrostatic pressures, aeration, and the efficiency of mixing in large-scale bioreactors. Besides, local [Formula: see text] levels might also act as metabolic inhibitors or transcriptional effectors triggering regulatory events inside the cells. This review gives an overview about fundamental physicochemical properties of [Formula: see text] in microbial and mammalian cultures effecting cellular physiology, production processes, metabolic activity, and transcriptional regulation. PMID- 26284244 TI - Hemodynamic Monitoring in the Critically Ill Patient - Current Status and Perspective. AB - In the critically ill patient, early and effective hemodynamic management including fluid therapy and administration of vasoactive drugs to maintain vital organ perfusion and oxygen delivery is mandatory. Understanding the different approaches in the management of critically ill patients during the resuscitation and further management is essential to initiate adequate context- and time specific interventions. Treatment of hemodynamic variables to achieve a balance between organ oxygen delivery and consumption is the cornerstone. In general, cardiac output is considered a major determinant of oxygen supply and thus its monitoring is regarded helpful. However, indicators of oxygen requirements are equally necessary to assess adequacy of oxygen supply. Currently, more and more less or even totally non-invasive monitoring systems have been developed and clinically introduced, but require validation in this particular patient population. Cardiac output monitors and surrogates of organ oxygenation only enable to adequately guide management, as patient's outcome is determined by acquisition and interpretation of accurate data, and finally suitable management decisions. This mini-review presents the currently available techniques in the field of hemodynamic monitoring in critically ill patients and briefly summarizes their advantages and limitations. PMID- 26284245 TI - A Hypothesis for Examining Skeletal Muscle Biopsy-Derived Sarcolemmal nNOSMU as Surrogate for Enteric nNOSalpha Function. AB - The pathophysiology of gastrointestinal motility disorders is controversial and largely unresolved. This provokes empiric approaches to patient management of these so-called functional gastrointestinal disorders. Preliminary evidence demonstrates that defects in neuronal nitric oxide synthase (nNOS) expression and function, the enzyme that synthesizes nitric oxide (NO), the key inhibitory neurotransmitter mediating mechano-electrical smooth muscle relaxation, is the major pathophysiological basis for sluggishness of oro-aboral transit of luminal contents. This opinion is an ansatz of the potential of skeletal muscle biopsy and examining sarcolemmal nNOSMU to provide complementary insights regarding nNOSalpha expression, localization, and function within enteric nerve terminals, the site of stimulated de novo NO synthesis. The main basis of this thesis is twofold: (a) the molecular similarity of the structures of nNOS alpha and MU, similar mechanisms of localizations to "active zones" of nitrergic synthesis, and same mechanisms of electron transfers during NO synthesis and (b) pragmatic difficulty to routinely obtain full-thickness biopsies of gastrointestinal tract, even in patients presenting with the most recalcitrant manifestations of stasis and delayed transit of luminal contents. This opinion attempts to provoke dialog whether this approach is feasible as a surrogate to predict catalytic potential of nNOSalpha and defects in nitrergic neurotransmission. This discussion makes an assumption that similar molecular mechanisms of nNOS defects shall be operant in both the enteric nerve terminals and the skeletal muscles. These overlaps of skeletal and gastrointestinal dysfunction are largely unknown, thus meriting that the thesis be validated in future by proof-of-principle experiments. PMID- 26284246 TI - Stem Cells and Their Mediators - Next Generation Therapy for Bronchopulmonary Dysplasia. AB - Bronchopulmonary dysplasia (BPD) remains a major complication of premature birth. Despite great achievements in perinatal medicine over the past decades, there is no treatment for BPD. Recent insights into the biology of stem/progenitor cells have ignited the hope of regenerating damaged organs. Animal experiments revealed promising lung protection/regeneration with stem/progenitor cells in experimental models of BPD and led to first clinical studies in infants. However, these therapies are still experimental and knowledge on the exact mechanisms of action of these cells is limited. Furthermore, heterogeneity of the therapeutic cell populations and missing potency assays currently limit our ability to predict a cell product's efficacy. Here, we review the therapeutic potential of mesenchymal stromal, endothelial progenitor, and amniotic epithelial cells for BPD. Current knowledge on the mechanisms behind the beneficial effects of stem cells is briefly summarized. Finally, we discuss the obstacles constraining their transition from bench-to-bedside and present potential approaches to overcome them. PMID- 26284247 TI - microRNA: Diagnostic Perspective. AB - Biomarkers are biological measures of a biological state. An ideal marker should be safe and easy to measure, cost efficient, modifiable with treatment, and consistent across gender and ethnic groups. To date, none of the available biomarkers satisfy all of these criteria. In addition, the major limitations of these markers are low specificity, sensitivity, and false positive results. Recently identified, microRNAs (miRNAs) are endogenous, evolutionarily conserved small non-coding RNA (about 22-25 nt long), also known as micro-coordinators of gene expression, which have been shown to be an effective tools to study the biology of diseases and to have great potential as novel diagnostic and prognostic biomarkers with high specificity and sensitivity. In fact, it has been demonstrated that miRNAs play a pivotal role in the regulation of a wide range of developmental and physiological processes and their deficiencies have been related to a number of disease. In addition, miRNAs are stable and can be easily isolated and measured from tissues and body fluids. In this review, we provide a perspective on emerging concepts and potential usefulness of miRNAs as diagnostic markers, emphasizing the involvement of specific miRNAs in particular tumor types, subtypes, cardiovascular diseases, diabetes, infectious diseases, and forensic test. PMID- 26284248 TI - Weight Self-Regulation Process in Adolescence: The Relationship between Control Weight Attitudes, Behaviors, and Body Weight Status. AB - Adolescents' self-control weight behaviors were assessed (N = 1961; 12-17 years old; 2007-2008) in the Balearic Islands, Spain. The study analyzed the relationships between body weight status, body image, and self-weight concern, and actual attempts to lose weight by restrained eating and/or increased exercising. In terms of regulatory focus theory (RFT), we considered that efforts to lose or to maintain weight (successful or failed) would be motivated either by a "promotion focus" (to show an attractive body), or a "prevention focus" (to avoid social rejection of fatness), or both. Results showed that 41% of overweight boys and 25% of obese boys stated that they had never made any attempt to lose weight, and 13 and 4% in females. Around half of overweight boys and around a quarter of obese boys stated that they were "Not at all" concerned about weight gain, and girls' percentages decreased to 13 and 11%, respectively. By contrast, 57% of normal weight girls monitored their weight and stated that they had tried to become slim at least once. Weight self-regulation in females attempted to combine diet and exercise, while boys relied almost exclusively on exercise. Apparent lack of consciousness of body weight status among overweight boys, and more important, subsequent absence of behaviors to reduce their weight clearly challenges efforts to prevent obesity. We argue that several causes may be involved in this outcome, including unconscious, emotional (self-defense), and cognitive (dissonance) mechanisms driven by perceived social stigmatization of obesity. The active participation of social values of male and female body image (strong vs. pretty), and the existence of social habituation to overweight are suggested. A better knowledge of psychosocial mechanisms underlying adolescent weight self-control may improve obesity epidemics. PMID- 26284249 TI - Mediterranean Diet: From a Healthy Diet to a Sustainable Dietary Pattern. AB - The notion of the Mediterranean diet has undergone a progressive evolution over the past 60 years, from a healthy dietary pattern to a sustainable dietary pattern, in which nutrition, food, cultures, people, environment, and sustainability all interact into a new model of a sustainable diet. An overview of the historical antecedents and recent increased interest in the Mediterranean diet is presented and challenges related to how to improve the sustainability of the Mediterranean diet are identified. Despite its increasing popularity worldwide, adherence to the Mediterranean diet model is decreasing for multifactorial influences - life styles changes, food globalization, economic, and socio-cultural factors. These changes pose serious threats to the preservation and transmission of the Mediterranean diet heritage to present and future generations. Today's challenge is to reverse such trends. A greater focus on the Mediterranean diet's potential as a sustainable dietary pattern, instead than just on its well-documented healthy benefits, can contribute to its enhancement. More cross-disciplinary studies on environmental, economic and socio cultural, and sustainability dimensions of the Mediterranean diet are foreseen as a critical need. PMID- 26284250 TI - Rhodiola rosea Exerts Antiviral Activity in Athletes Following a Competitive Marathon Race. AB - Rhodiola rosea, a medicinal plant with demonstrated adaptogenic properties, has recently been reported to contain active compounds with antimicrobial activity. The goal of this study was to measure the antiviral and antibacterial properties of the bioactive metabolites of Rhodiola rosea in the serum of experienced marathon runners following supplementation. Marathon runners, randomly divided into two groups, ingested 600 mg/day of Rhodiola rosea (n = 24, 6 female, 18 male) or placebo (n = 24, 7 females, 17 males) for 30 days prior to, the day of, and 7 days post-marathon. Blood serum samples were collected the day before, 15 min post-, and 1.5 h post-marathon. Serum from Rhodiola rosea-supplemented runners collected after marathon running did not attenuate the marathon-induced susceptibility of HeLa cells to killing by vesicular stomatitis virus. However, the use of Rhodiola rosea induced antiviral activity at early times post infection by delaying an exercise-dependent increase in virus replication (P = 0.013 compared to placebo). Serum from both groups collected 15 min post-marathon significantly promoted the growth of Escherichia coli in culture as compared to serum collected the day before the marathon (P = 0.003, all subjects). Furthermore, the serum from subjects ingesting Rhodiola rosea did not display antibacterial properties at any time point as indicated by a lack of group differences immediately (P = 0.785) or 1.5 h (P = 0.633) post-marathon. These results indicate that bioactive compounds in the serum of subjects ingesting Rhodiola rosea may exert protective effects against virus replication following intense and prolonged exercise by inducing antiviral activity. PMID- 26284251 TI - Mechanical Ventricular Assistance as Destination Therapy for End-Stage Heart Failure: Has it Become a First Line Therapy? AB - Patients with end-stage heart failure have poor quality of life and prognosis. Therapeutic options are scarce and are not available for all. Only few patients can be transplanted every year. Several medical and surgical strategies have shown limited ability to influence prognosis and quality of life. In the past years, technological progress has realized devices capable of providing appropriate hemodynamic stabilization and recovery of secondary organ failure. Recently, these devices have been assessed as definitive treatment for patients who do not qualify for transplantation or/and instead to transplantation ("destination therapy"). This indication is increasingly considered following the results of newest clinical study reporting long-term survival without device correlated adverse events using last generation devices, and acceptable quality of life. The current knowledge about destination therapy and some original data from the DAVID Study (an Italian multicenter prospective study designed to evaluate the patient's survival rate and quality of life of patients implanted with these new devices as long-term support or destination therapy) are summarized herein. KEY POINTS: -End-stage heart failure (NYHA class IV or stage D) is a vastly growing problem, with a poor prognosis and limited therapeutic options.-Heart Transplantation is nowadays the "gold standard" treatment albeit its inability to serve to the current demand let alone the future one.-The REMATCH study has demonstrated that first generation implantable devices, even with their high number of complications (infectious and thromboembolic events), allowed an improvement of quality and duration of life compared to medical therapy. Further studies have shown that the evolution of VAD technology has reduced device-related complications and consequently improved survival and quality of life of patients with results, according to some authors, similar to cardiac transplantation at least at 2 years from the implantation.-Biotechnology advancements have led to the creation of a new generation of implantable mechanical assist devices: the continuous-flow rotary pumps. Recently entered into clinical use, they seem to represent a promising solution to end -stage heart failure allowing long-term assistance and an adequate standard of living (Destination Therapy/Bridge to Life).-The DAVID Study, an Italian multicenter prospective study, reports encouraging results in terms of late outcome and quality of life in patients implanted with newest continuous-flow devices as destination therapy. More and more numerous studies are needed to confirm our initial data and for laying the foundations for this new therapeutic frontier face to cardiac transplantation. PMID- 26284252 TI - Applying Advanced Imaging Techniques to a Murine Model of Orthotopic Osteosarcoma. AB - INTRODUCTION: Reliable animal models are required to evaluate novel treatments for osteosarcoma. In this study, the aim was to implement advanced imaging techniques in a murine model of orthotopic osteosarcoma to improve disease modeling and the assessment of primary and metastatic disease. MATERIALS AND METHODS: Intra-tibial injection of luciferase-tagged OPGR80 murine osteosarcoma cells was performed in Balb/c nude mice. Treatment agent [pigment epithelium derived factor (PEDF)] was delivered to the peritoneal cavity. Primary tumors and metastases were evaluated by in vivo bioluminescent assays, micro-computed tomography, [(18)F]-Fluoride-PET and [(18)F]-FDG-PET. RESULTS: [(18)F]-Fluoride PET was more sensitive than [(18)F]-FDG-PET for detecting early disease. Both [(18)F]-Fluoride-PET and [(18)F]-FDG-PET showed progressive disease in the model, with fourfold and twofold increases in standardized uptake value (p < 0.05) by the study endpoint, respectively. In vivo bioluminescent assay showed that systemically delivered PEDF inhibited growth of primary osteosarcoma. DISCUSSION: Application of [(18)F]-Fluoride-PET and [(18)F]-FDG-PET to an established murine model of orthotopic osteosarcoma has improved the assessment of disease. The use of targeted imaging should prove beneficial for the evaluation of new approaches to osteosarcoma therapy. PMID- 26284253 TI - The Effect of Saline Coolant on Temperature Levels during Decortication with a Midas Rex: An in Vitro Model Using Sheep Cervical Vertebrae. AB - Decortication of bone with a high-speed burr in the absence of coolant may lead to local thermal necrosis and decreased healing ability, which may negatively impact clinical outcome. Little data are available on the impact of applying a coolant during the burring process. This study aims to establish an in vitro model to quantitatively assess peak temperatures during endplate preparation with a high-speed burr. Six sheep cervical vertebrae were dissected and mounted. Both end plates were used to give a total of 12 sites. Two thermocouples were inserted into each vertebra, 2 mm below the end plate surface and a thermal camera set up to measure surface temperature. A 3 mm high-pneumatic speed burr (Midas Rex, Medtronic, Fort Worth, TX, USA) was used to decorticate the bone in a side to side sweeping pattern, using a matchstick burr (M-8/9MH30) with light pressure. This procedure was repeated while dripping saline onto the burr and bone. Data were compared between groups using a Student's t-test. Application of coolant at the bone-burr interface during decortication resulted in a significant decrease in final temperature. Without coolant, maximum temperatures 2 mm from the surface were not sufficient to cause thermal osteonecrosis, although peak surface temperatures would cause local damage. The use of a high-speed burr provides a quick and an effective method of vertebral end plate preparation. Thermal damage to the bone can be minimized through the use of light pressure and saline coolant. This has implications for any bone preparation performed with a high speed burr. PMID- 26284255 TI - Protein plasticity underlines activation and function of ATP-independent chaperones. AB - One of the key issues in biology is to understand how cells cope with protein unfolding caused by changes in their environment. Self-protection is the natural immediate response to any sudden threat and for cells the critical issue is to prevent aggregation of existing proteins. Cellular response to stress is therefore indistinguishably linked to molecular chaperones, which are the first line of defense and function to efficiently recognize misfolded proteins and prevent their aggregation. One of the major protein families that act as cellular guards includes a group of ATP-independent chaperones, which facilitate protein folding without the consumption of ATP. This review will present fascinating insights into the diversity of ATP-independent chaperones, and the variety of mechanisms by which structural plasticity is utilized in the fine-tuning of chaperone activity, as well as in crosstalk within the proteostasis network. Research into this intriguing class of chaperones has introduced new concepts of stress response to a changing cellular environment, and paved the way to uncover how this environment affects protein folding. PMID- 26284254 TI - NMR chemical shift pattern changed by ammonium sulfate precipitation in cyanobacterial phytochrome Cph1. AB - Phytochromes are dimeric biliprotein photoreceptors exhibiting characteristic red/far-red photocycles. Full-length cyanobacterial phytochrome Cph1 from Synechocystis 6803 is soluble initially but tends to aggregate in a concentration dependent manner, hampering attempts to solve the structure using NMR and crystallization methods. Otherwise, the Cph1 sensory module (Cph1Delta2), photochemically indistinguishable from the native protein and used extensively in structural and other studies, can be purified to homogeneity in >10 mg amounts at mM concentrations quite easily. Bulk precipitation of full-length Cph1 by ammonium sulfate (AmS) was expected to allow us to produce samples for solid state magic-angle spinning (MAS) NMR from dilute solutions before significant aggregation began. It was not clear, however, what effects the process of partial dehydration might have on the molecular structure. Here we test this by running solid-state MAS NMR experiments on AmS-precipitated Cph1Delta2 in its red absorbing Pr state carrying uniformly (13)C/(15)N-labeled phycocyanobilin (PCB) chromophore. 2D (13)C-(13)C correlation experiments allowed a complete assignment of (13)C responses of the chromophore. Upon precipitation, (13)C chemical shifts for most of PCB carbons move upfield, in which we found major changes for C4 and C6 atoms associated with the A-ring positioning. Further, the broad spectral lines seen in the AmS (13)C spectrum reflect primarily the extensive inhomogeneous broadening presumably due to an increase in the distribution of conformational states in the protein, in which less free water is available to partake in the hydration shells. Our data suggest that the effect of dehydration process indeed leads to changes of electronic structure of the bilin chromophore and a decrease in its mobility within the binding pocket, but not restricted to the protein surface. The extent of the changes induced differs from the freezing process of the solution samples routinely used in previous MAS NMR and crystallographic studies. AmS precipitation might nevertheless provide useful protein structure/functional information for full-length Cph1 in cases where neither X-ray crystallography nor conventional NMR methods are available. PMID- 26284256 TI - Neisseria sicca Endocarditis Presenting as Multiple Embolic Brain Infarcts. AB - A 58 year old male presented with a 14 day history of progressive forgetfulness and aggressiveness. He had a history of human immunodeficiency virus infection, ischemic cardiomyopathy, and a myxomatous mitral valve (status post Saint Jude's mitral valve replacement 8 years before presentation). International normalized ratio was supra-therapeatutic on admission. A non-contrast computed tomography of the brain indicated multiple infarcts with hemorrhagic conversion. The source was later found to be a rare case of Neisseria sicca endocarditis. PMID- 26284257 TI - Molecular Detection and Characterization of Mycoplasma pneumoniae Among Patients Hospitalized With Community-Acquired Pneumonia in the United States. AB - Background. Mycoplasma pneumoniae is a common cause of community-acquired pneumonia (CAP). The molecular characteristics of M pneumoniae detected in patients hospitalized with CAP in the United States are poorly described. Methods. We performed molecular characterization of M pneumoniae in nasopharyngeal/oropharyngeal swabs from children and adults hospitalized with CAP in the Centers for Disease Control and Prevention Etiology of Pneumonia in the Community (EPIC) study, including P1 typing, multilocus variable-number tandem repeat analysis (MLVA), and macrolide susceptibility genotyping. Results. Of 216 M pneumoniae polymerase chain reaction-positive specimens, 40 (18.5%) were obtained from adults and 176 (81.5%) from children. P1 type distribution differed between adults (64% type 1 and 36% type 2) and children (84% type 1, 13% type 2, and 3% variant) (P < .05) and among sites (P < .01). Significant differences in the proportions of MLVA types 4/5/7/2 and 3/5/6/2 were also observed by age group (P < .01) and site (P < .01). A macrolide-resistant genotype was identified in 7 (3.5%) specimens, 5 of which were from patients who had recently received macrolide therapy. No significant differences in clinical characteristics were identified among patients with various strain types or between macrolide resistant and -sensitive M pneumoniae infections. Conclusions. The P1 type 1 genotype and MLVA type 4/5/7/2 predominated, but there were differences between children and adults and among sites. Macrolide resistance was rare. Differences in strain types did not appear to be associated with differences in clinical outcomes. Whole genome sequencing of M pneumoniae may help identify better ways to characterize strains. PMID- 26284260 TI - High-Throughput Minigenome System for Identifying Small-Molecule Inhibitors of Ebola Virus Replication. AB - Ebola virus (EBOV), a member of the family Filoviridae, is a nonsegmented negative-sense RNA virus that causes severe, often lethal, disease in humans. EBOV RNA synthesis is carried out by a complex that includes several viral proteins. The function of this machinery is essential for viral gene expression and viral replication and is therefore a potential target for antivirals. We developed and optimized a high-throughput screening (HTS) assay based on an EBOV minigenome assay, which assesses the function of the polymerase complex. The assay is robust in 384-well format and displays a large signal to background ratio and high Z-factor values. We performed a pilot screen of 2080 bioactive compounds, identifying 31 hits (1.5% of the library) with >70% inhibition of EBOV minigenome activity. We further identified eight compounds with 50% inhibitory concentrations below their 50% cytotoxic concentrations, five of which had selectivity index (SI) values >10, suggesting specificity against the EBOV polymerase complex. These included an inhibitor of inosine monophosphate dehydrogenase, a target known to modulate the EBOV replication complex. They also included novel classes of inhibitors, including inhibitors of protein synthesis and hypoxia inducible factor-1. Five compounds were tested for their ability to inhibit replication of a recombinant EBOV that expresses GFP (EBOV-GFP), and four inhibited EBOV-GFP growth at sub-cytotoxic concentrations. These data demonstrate the utility of the HTS minigenome assay for drug discovery and suggest potential directions for antifiloviral drug development. PMID- 26284259 TI - Predicting Risk of End-Stage Liver Disease in Antiretroviral-Treated Human Immunodeficiency Virus/Hepatitis C Virus-Coinfected Patients. AB - Background. End-stage liver disease (ESLD) is an important cause of morbidity among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. Quantifying the risk of this outcome over time could help determine which coinfected patients should be targeted for risk factor modification and HCV treatment. We evaluated demographic, clinical, and laboratory variables to predict risk of ESLD in HIV/HCV-coinfected patients receiving antiretroviral therapy (ART). Methods. We conducted a retrospective cohort study among 6016 HIV/HCV-coinfected patients who received ART within the Veterans Health Administration between 1997 and 2010. The main outcome was incident ESLD, defined by hepatic decompensation, hepatocellular carcinoma, or liver-related death. Cox regression was used to develop prognostic models based on baseline demographic, clinical, and laboratory variables, including FIB-4 and aspartate aminotransferase-to-platelet ratio index, previously validated markers of hepatic fibrosis. Model performance was assessed by discrimination and decision curve analysis. Results. Among 6016 HIV/HCV patients, 532 (8.8%) developed ESLD over a median of 6.6 years. A model comprising FIB-4 and race had modest discrimination for ESLD (c-statistic, 0.73) and higher net benefit than alternative strategies of treating no or all coinfected patients at relevant risk thresholds. For FIB-4 >3.25, ESLD risk ranged from 7.9% at 1 year to 26.0% at 5 years among non-blacks and from 2.4% at 1 year to 14.0% at 5 years among blacks. Conclusions. Race and FIB-4 provided important predictive information on ESLD risk among HIV/HCV patients. Estimating risk of ESLD using these variables could help direct HCV treatment decisions among HIV/HCV-coinfected patients. PMID- 26284261 TI - In vitro fluorescence studies of transcription factor IIB-DNA interaction. AB - General transcription factor TFIIB is one of the basal constituents of the preinitiation complex of eukaryotic RNA polymerase II, acting as a bridge between the preinitiation complex and the polymerase, and binding promoter DNA in an asymmetric manner, thereby defining the direction of the transcription. Methods of fluorescence spectroscopy together with circular dichroism spectroscopy were used to observe conformational changes in the structure of recombinant human TFIIB after binding to specific DNA sequence. To facilitate the exploration of the structural changes, several site-directed mutations have been introduced altering the fluorescence properties of the protein. Our observations showed that binding of specific DNA sequences changed the protein structure and dynamics, and TFIIB may exist in two conformational states, which can be described by a different microenvironment of W52. Fluorescence studies using both intrinsic and exogenous fluorophores showed that these changes significantly depended on the recognition sequence and concerned various regions of the protein, including those interacting with other transcription factors and RNA polymerase II. DNA binding can cause rearrangements in regions of proteins interacting with the polymerase in a manner dependent on the recognized sequences, and therefore, influence the gene expression. PMID- 26284263 TI - The effect of differentiation agents on inflammatory and oxidative responses of the human neuroblastoma cell line SK-N-SH. AB - Obtaining a suitable experimental cellular model is a major problem for neuroscience studies. Neuroblastoma cell lines have been often applied in studies related to pathological disorders of nervous system. However, in the search for an ideal model, these cells must be differentiated to cancel their tumor character. The subsequent reactions that are caused by differentiation are not always indifferent to the same model. We evaluated the effect of two well known substances, used for SH-N-SK cell line differentiation, retinoic acid (RA) and phorbol-12-myristate-13-acetate (PMA), on the induction of pro-inflammatory and pro-oxidative reactions in these cells. Cells differentiated with PMA were able to produce significantly higher amounts of pro-inflammatory cytokines whereas the release of nitric oxide radicals was similar to that in undifferentiated cells. On the contrary, in RA-differentiated cells no significant changes in cytokine production were observed and the nitric oxide release was decreased. Additionally, the RA-differentiated neuronal model was more sensible to lipopolysaccharide stimulation, producing pro-inflammatory cytokines abundantly. These results suggest that RA-differentiated SH-N-SK cells provide a more suitable experimental model for the study of molecular and cellular mechanisms of the inflammation and oxidative stress in neuronal cells. PMID- 26284265 TI - Thank You, Francois! PMID- 26284262 TI - Analysis of genes involved in response to doxorubicin and a GD2 ganglioside specific 14G2a monoclonal antibody in IMR-32 human neuroblastoma cells. AB - Neuroblastoma is the most common extra-cranial solid tumor of childhood and it is characterized by the presence of a glycosphingolipid, GD2 ganglioside. Monoclonal antibodies targeting the antigen are currently tested in clinical trials. Additionally, several research groups reported results revealing that ganglioside specific antibodies can affect cellular signaling and cause direct cytotoxicity against tumor cells. To shed more light on gene expression signatures of tumor cells, we used microarrays to analyze changes of transcriptome in IMR-32 human neuroblastoma cell cultures treated with doxorubicin (DOX) or a mouse monoclonal antibody binding to GD2 ganglioside 14G2a (mAb) for 24 h. The obtained results highlight that disparate cellular pathways are regulated by doxorubicin and 14G2a. Next, we used RT-PCR to verify mRNA levels of selected DOX-responsive genes such as RPS27L, PPM1D, SESN1, CDKN1A, TNFSF10B, and 14G2a-responsive genes such as SVIL, JUN, RASSF6, TLX2, ID1. Then, we applied western blot and analyzed levels of RPS27L, PPM1D, sestrin 1 proteins after DOX-treatment. Additionally, we aimed to measure effects of doxorubicin and topotecan (TPT) and 14G2a on expression of a novel human NDUFAF2 gene encoding for mimitin protein (MYC induced mitochondrial protein) and correlate it with expression of the MYCN gene. We showed that expression of both genes was concomitantly decreased in the 14G2a treated IMR-32 cells after 24 h and 48 h. Our results extend knowledge on gene expression profiles after application of DOX and 14G2a in our model and reveal promising candidates for further research aimed at finding novel anti neuroblastoma targets. PMID- 26284258 TI - Strong Impact of Smoking on Multimorbidity and Cardiovascular Risk Among Human Immunodeficiency Virus-Infected Individuals in Comparison With the General Population. AB - Background. Although acquired immune deficiency syndrome-associated morbidity has diminished due to excellent viral control, multimorbidity may be increasing among human immunodeficiency virus (HIV)-infected persons compared with the general population. Methods. We assessed the prevalence of comorbidities and multimorbidity in participants of the Swiss HIV Cohort Study (SHCS) compared with the population-based CoLaus study and the primary care-based FIRE (Family Medicine ICPC-Research using Electronic Medical Records) records. The incidence of the respective endpoints were assessed among SHCS and CoLaus participants. Poisson regression models were adjusted for age, sex, body mass index, and smoking. Results. Overall, 74 291 participants contributed data to prevalence analyses (3230 HIV-infected; 71 061 controls). In CoLaus, FIRE, and SHCS, multimorbidity was present among 26%, 13%, and 27% of participants. Compared with nonsmoking individuals from CoLaus, the incidence of cardiovascular disease was elevated among smoking individuals but independent of HIV status (HIV-negative smoking: incidence rate ratio [IRR] = 1.7, 95% confidence interval [CI] = 1.2 2.5; HIV-positive smoking: IRR = 1.7, 95% CI = 1.1-2.6; HIV-positive nonsmoking: IRR = 0.79, 95% CI = 0.44-1.4). Compared with nonsmoking HIV-negative persons, multivariable Poisson regression identified associations of HIV infection with hypertension (nonsmoking: IRR = 1.9, 95% CI = 1.5-2.4; smoking: IRR = 2.0, 95% CI = 1.6-2.4), kidney (nonsmoking: IRR = 2.7, 95% CI = 1.9-3.8; smoking: IRR = 2.6, 95% CI = 1.9-3.6), and liver disease (nonsmoking: IRR = 1.8, 95% CI = 1.4-2.4; smoking: IRR = 1.7, 95% CI = 1.4-2.2). No evidence was found for an association of HIV-infection or smoking with diabetes mellitus. Conclusions. Multimorbidity is more prevalent and incident in HIV-positive compared with HIV-negative individuals. Smoking, but not HIV status, has a strong impact on cardiovascular risk and multimorbidity. PMID- 26284264 TI - Characterization of thiamine uptake and utilization in Candida spp. subjected to oxidative stress. AB - Candida species are associated with an increasing number of life-threatening infections (candidiases), mainly due to the high resistance of these yeast-like fungi to antifungal drugs and oxidative stress. Recently, thiamine (vitamin B1) was found to alleviate stress responses in Saccharomyces cerevisiae; however, thiamine influence on defense systems in pathogenic fungi has never been investigated. The current work was aimed to elucidate the role of thiamine in stress reactions of C. albicans, C. glabrata, C. tropicalis and C. dubliniensis, subjected to hydrogen peroxide treatment. As compared to S. cerevisiae, Candida strains exposed to oxidative stress showed: (i) a much higher dependence on exogenous thiamine; (ii) an increased demand for thiamine diphosphate (TDP) and TDP-dependent enzyme, transketolase; (iii) no changes in gene expression of selected stress markers - superoxide dismutase and catalase - depending on thiamine availability in medium; (iv) a similar decrease of reactive oxygen species (ROS) generation in the presence of thiamine. Moreover, the addition of therapeutic doses of thiamine to yeast culture medium revealed differences in its accumulation between various Candida species. The current findings implicate that the protective action of thiamine observed in S. cerevisiae differs significantly form that in pathogenic Candida strains, both in terms of the cofactor functions of TDP and the effects on fungal defense systems. PMID- 26284267 TI - Surface Conditioning Protocol for the Adhesion of Resin-based Materials to Glassy Matrix Ceramics: How to Condition and Why? PMID- 26284268 TI - [Career planning in medicine. Prof. Dr. Joachim Mossner interviewed by Anna Wolter]. PMID- 26284269 TI - ARID2, p110alpha, p53, and beta-catenin protein expression in hepatocellular carcinoma and clinicopathologic implications. AB - ARID2 (ARID2), CTNNB1 (beta catenin), tumor protein 53 (p53), and PIK3CA (p110alpha) mutations are implicated in hepatocellular carcinoma (HCC); and previous work has contributed to thorough molecular characterization of these events. However, studies that assess the impact of these mutations on downstream protein expression, especially those that evaluate all 4 cancer markers simultaneously, are relatively lacking. Hence, the present study uses immunohistochemistry to assess protein expression patterns of ARID2, beta catenin, p53, and p110alpha in HCCs and adjacent nonneoplastic cirrhotic tissues from 58 explanted livers. Notably, this study is the first to our knowledge to investigate ARID2 protein expression in the liver. The frequency of ARID2 mutations detected using our immunohistochemistry method was similar to that reported in previous molecular studies. Furthermore, we found that loss of ARID2 protein expression may be associated with recurrence, although further studies must be done to validate these findings in a larger population. We found that expression patterns of the 4 cancer markers were independent of each other, suggesting separate pathways of hepatocarcinogenesis. We also did not observe an association between viral etiology and protein expression. Consistent with previous studies, overexpression of p53 correlated with poor differentiation. Lastly, 17.5% of HCCs paradoxically had diffuse loss of the oncoprotein p110alpha compared with strong expression in background cirrhotic liver. The exact mechanism is unclear, but enigmatic loss of oncoprotein function has been described in other carcinomas and could potentially have significant implications for the use of mechanistic target of rapamycin (mTOR) drug therapies. PMID- 26284270 TI - The role of the medial ligaments in lateral stabilization of the ankle joint: an in vitro study. AB - PURPOSE: The deltoid ligament complex is known as medial stabilizer in the ankle against pronation/eversion. Lateral dual-ligament laxity often results in chronic ankle instability with recurring ankle sprain trauma. The goal of this study is to examine the lateral stabilizing role of the deltoid ligament complex against supination/inversion in case of existing lateral ligament instability. METHODS: A torsion simulation was performed on 12 fresh human lower leg cadaver specimens in a loading frame and a specially designed mounting platform. The preset torsion between tibia and calcaneus was primarily set at 30 degrees of internal rotation on specimen in plantar flexion and hindfoot inversion. The measured variable was the resisting torque recorded around mechanical tibial axis, which ensures stability in ankle sprain trauma. The first series of measurements were performed on healthy specimens and the following after transecting structures in following order: anterior talofibular ligament (ATFL) in combination with calcaneofibular ligament (CFL), followed by anterior tibiotalar ligament and posterior tibiotalar ligament and finally tibiocalcaneal ligament (TCL). RESULTS: The combined lateral ATFL and CFL instability showed a decrease in the resisting torque, which ensures stability in ankle sprain trauma. Only a transection of TCL (superficial layer of deltoid ligament complex) with existing lateral dual-ligament instability results in a significant decrease in torque (p<0.0001). CONCLUSION: The goal of the study was to provide the orthopaedic and/or trauma surgeon with quantitative data that may be referred to the substantial stabilizing effect of TCL against supination/inversion in the ankle joint in case of repetitive sprain trauma at a present lateral ligament lesion. Diagnostics of and treatment for lateral ligament instability need to consider the deltoid ligament complex,especially TCL in clinical routine. PMID- 26284272 TI - [Coloproctology in the course of time]. PMID- 26284271 TI - Inter- and intrarater reliability of four single-legged hop tests and isokinetic muscle torque measurements in children. AB - PURPOSE: Single-legged hop tests and isokinetic muscle torque are common outcome measures in the evaluation of knee function. The reliability of the single-legged hop tests in children has not been documented. The aim was to examine inter- and intrarater reliability of four single-legged hop tests and isokinetic muscle torque measurements in children. METHODS: Twenty-eight sports-active children (12.4 +/- 0.3 years old) were tested three times in two test sessions separated by 1 week. They performed four single-legged hop tests and concentric isokinetic torque measurements during knee extension and flexion. Inter- and intrarater reliability were calculated using the intraclass correlation coefficient (ICC 2,1). Relative terms of the standard error of measurement (SEM %) and smallest real difference(SRD %) were emphasized to allow comparison between the different variables. RESULTS: Twenty-six children were included for statistical analysis. ICCs for inter- and intrarater reliability were moderate to high for the hop tests (0.62-.91) and isokinetic measurements (0.76-0.87). SEMs % were low for the hop tests (3.9-7.4 %) and the isokinetic measurements (5.2-8.9 %). SRDs % were 20.5 % or less for the hop tests, 15.7 % or less for knee extension, and 24.6 % or less for knee flexion. CONCLUSION: The single-legged hop tests and isokinetic muscle torque measurements demonstrated moderate-to high reliability with low measurement error in sports-active children. A change above 20.5 % for the single legged hop tests, 15.7 % for knee extension, and 24.6 % for knee flexion is necessary to represent a real change in knee function. Level of evidence III. PMID- 26284273 TI - Prehospital stabilization of unstable neonates. They're prone to rapid deterioration; here's how to handle them. PMID- 26284274 TI - LOCATION, LOCATION, LOCATION. Site of Service and the Search for Value. PMID- 26284275 TI - [Envy you have to acquire.....]. PMID- 26284276 TI - [A contract doctor is not a doctor of choice]. PMID- 26284277 TI - [Successful communication in all situations -- circumnavigate pitfalls confidently]. PMID- 26284278 TI - Nursing2015 isn't just for nurses. PMID- 26284279 TI - In memory of George O. Waring III. PMID- 26284280 TI - Response to Letter by Powers Regarding Article, "Failure of Cerebral Hemodynamic Selection in General or of Specific Positron Emission Tomography Methodology? Carotid Occlusion Surgery Study (COSS). PMID- 26284281 TI - Response to Role of Epithelial Sodium Channels in the Renal Myogenic Response? PMID- 26284282 TI - Response to Role of Epithelial Sodium Channels in the Renal Myogenic Response? PMID- 26284283 TI - Hierarchical Assembly of alpha-Fe2O3 Nanosheets on SnO22Hollow Nanospheres with Enhanced Ethanol Sensing Properties. AB - We present the preparation of a hierarchical nanoheterostructure consisting of inner SnO2 hollow spheres (SHS) surrounded by an outer alpha-Fe2O3 nanosheet (FNS). Deposition of the FNS on the SHS outer surface was achieved by a facile microwave hydrothermal reaction to generate a double-shell SHS@FNS nanostructure. Such a composite with novel heterostructure acted as a sensing material for gas sensors. Significantly, the hierarchical composites exhibit excellent sensing performance toward ethanol, which is superior to the single component (SHS), mainly because of the synergistic effect and heterojunction. PMID- 26284284 TI - Forearm vasodilator reactivity in healthy male carriers of the 3q22.3 rs9818870 polymorphism. AB - BACKGROUND: A genome wide association study has identified a robust risk locus for cardiovascular disease on 3q22.3. However, the mechanisms by which the [C]/[T] polymorphism rs9818870 increases cardiovascular risk are unknown. This forearm blood flow (FBF) study addressed the question if the genetic association with cardiovascular disease in patients is preceded by incipient vasodilator impairment in young, healthy carriers of this new risk locus on chromosome 3. MATERIALS AND METHODS: After a pre-screening of 74 subjects 17 male healthy volunteers homozygous/heterozygous for a single nucleotide polymorphism (SNP) risk allele on 3q22.3 and a control group of 17 healthy volunteers not carrying the allele were included into this case-control study. RESULTS: Forearm vascular endothelium-dependent and -independent vasodilator responses were in the normal range in both groups, although endothelium-dependent FBF reactivity to acetylcholine was significantly higher in SNP carriers of the risk allele. CONCLUSION: The augmented endothelium-dependent vasodilation of the forearm resistance vasculature does not support the presence of endothelial dysfunction in young SNP carriers and indicates that other mechanisms are responsible for the strong association between coronary artery diseases and the rs9818870 polymorphism, located on 3q22.3. PMID- 26284285 TI - A Static Picture of the Relaxation and Intersystem Crossing Mechanisms of Photoexcited 2-Thiouracil. AB - Accurate excited-state quantum chemical calculations on 2-thiouracil, employing large active spaces and up to quadruple-zeta quality basis sets in multistate complete active space perturbation theory calculations, are reported. The results suggest that the main relaxation path for 2-thiouracil after photoexcitation should be S2 -> S1 -> T2 -> T1, and that this relaxation occurs on a subpicosecond time scale. There are two deactivation pathways from the initially excited bright S2 state to S1, one of which is nearly barrierless and should promote ultrafast internal conversion. After relaxation to the S1 minimum, small singlet-triplet energy gaps and spin-orbit couplings of about 130 cm(-1) are expected to facilitate intersystem crossing to T2, from where very fast internal conversion to T1 occurs. An important finding is that 2-thiouracil shows strong pyramidalization at the carbon atom of the thiocarbonyl group in several excited states. PMID- 26284286 TI - Creating New Economic Incentives for Repurposing Generic Drugs for Unsolved Diseases Using Social Finance. AB - Repurposing research improves patient lives by taking drugs approved for one disease and clinically testing them to create a treatment for a different disease. Repurposing drugs that are generic, inexpensive, and widely available and that can be taken in their current dosage and formulation in the new indication provide a quick, affordable, and effective way to create "new" treatments. However, generic drug repurposing often provides no profit potential, and so there is no economic incentive for industry to pursue this, and philanthropy and government funds are often insufficient. One way to create new economic incentive for the repurposing of generic drugs is through social finance. This perspective describes how social finance can create a new economic incentive by using a social impact bond, or similar financial structure, to repay for-profit investors who fund the repurposing research from the proceeds of healthcare cost reductions generated when these affordable, effective, and widely available repurposed therapies improve healthcare outcomes. PMID- 26284287 TI - Hoxb1 regulates proliferation and differentiation of second heart field progenitors in pharyngeal mesoderm and genetically interacts with Hoxa1 during cardiac outflow tract development. AB - Outflow tract (OFT) anomalies are among the most common congenital heart defects found at birth. The embryonic OFT grows by the progressive addition of cardiac progenitors, termed the second heart field (SHF), which originate from splanchnic pharyngeal mesoderm. Development of the SHF is controlled by multiple intercellular signals and transcription factors; however the relationship between different SHF regulators remains unclear. We have recently shown that Hoxa1 and Hoxb1 are expressed in a sub-population of the SHF contributing to the OFT. Here, we report that Hoxb1 deficiency results in a shorter OFT and ventricular septal defects (VSD). Mechanistically, we show that both FGF/ERK and BMP/SMAD signaling, which regulate proliferation and differentiation of cardiac progenitor cells and OFT morphogenesis, are enhanced in the pharyngeal region in Hoxb1 mutants. Absence of Hoxb1 also perturbed SHF development through premature myocardial differentiation. Hence, the positioning and remodeling of the mutant OFT is disrupted. Hoxa1(-/-) embryos, in contrast, have low percentage of VSD and normal SHF development. However, compound Hoxa1(-/-); Hoxb1(+/-) embryos display OFT defects associated with premature SHF differentiation, demonstrating redundant roles of these factors during OFT development. Our findings provide new insights into the gene regulatory network controlling SHF and OFT formation. PMID- 26284288 TI - Is Internet Addiction Prevalent Among Methadone Maintenance Treatment Patients? Data from Las Vegas and Tel Aviv. AB - Internet addiction is known to be associated with depression. The Internet Addiction Test (IAT) and the Center for Epidemiologic Studies Depression scale (CES-D) for depression were studied among non-selective methadone maintenance treatment patients from the United States (n = 164) and Israel (n = 113). Thirty percent were not exposed to the internet, and 2.9% (n = 8) had an "occasional/frequent problem." The IAT and CES-D scores correlated significantly (p = .03). The non-exposed group was older, less educated, and had more benzodiazepine abusers. Unlike other behavioral addictions that characterized these patients, the internet addiction problem is rare, but should not be ignored. PMID- 26284289 TI - Rapid and Robust Polyprotein Production Facilitates Single-Molecule Mechanical Characterization of beta-Barrel Assembly Machinery Polypeptide Transport Associated Domains. AB - Single-molecule force spectroscopy by atomic force microscopy exploits the use of multimeric protein constructs, namely, polyproteins, to decrease the impact of nonspecific interactions, to improve data accumulation, and to allow the accommodation of benchmarking reference domains within the construct. However, methods to generate such constructs are either time- and labor-intensive or lack control over the length or the domain sequence of the obtained construct. Here, we describe an approach that addresses both of these shortcomings that uses Gibson assembly (GA) to generate a defined recombinant polyprotein rapidly using linker sequences. To demonstrate the feasibility of this approach, we used GA to make a polyprotein composed of alternating domains of I27 and TmCsp, (I27-TmCsp)3 I27)(GA), and showed the mechanical fingerprint, mechanical strength, and pulling speed dependence are the same as an analogous polyprotein constructed using the classical approach. After this benchmarking, we exploited this approach to facilitiate the mechanical characterization of POTRA domain 2 of BamA from E. coli (EcPOTRA2) by assembling the polyprotein (I27-EcPOTRA2)3-I27(GA). We show that, as predicted from the alpha + beta topology, EcPOTRA2 domains are mechanically robust over a wide range of pulling speeds. Furthermore, we identify a clear correlation between mechanical robustness and brittleness for a range of other alpha + beta proteins that contain the structural feature of proximal terminal beta-strands in parallel geometry. We thus demonstrate that the GA approach is a powerful tool, as it circumvents the usual time- and labor intensive polyprotein production process and allows for rapid production of new constructs for single-molecule studies. As shown for EcPOTRA2, this approach allows the exploration of the mechanical properties of a greater number of proteins and their variants. This improves our understanding of the relationship between structure and mechanical strength, increasing our ability to design proteins with tailored mechanical properties. PMID- 26284290 TI - Saccade-Related Potentials During Eye-Hand Coordination: Effects of Hand Movements on Saccade Preparation. AB - This study investigated the effect of hand movements on behavioral and electrophysiological parameters of saccade preparation. While event-related potentials were recorded in 17 subjects, they performed saccades to a visual target either together with a hand movement in the same direction, a hand movement in the opposite direction, a hand movement to a third, independent direction, or without any accompanying hand movements. Saccade latencies increased with any kind of accompanying hand movement. Both saccade and manual latencies were largest when both movements aimed at opposite directions. In contrast, saccade-related potentials indicating preparatory activity were mainly affected by hand movements in the same direction. The data suggest that concomitant hand movements interfere with saccade preparation, particularly when the two movements involve motor preparations that access the same visual stimulus. This indicates that saccade preparation is continually informed about hand movement preparation. PMID- 26284291 TI - Fat-Free Mass Changes During Ketogenic Diets and the Potential Role of Resistance Training. AB - Low-carbohydrate and very-low-carbohydrate diets are often used as weight-loss strategies by exercising individuals and athletes. Very-low-carbohydrate diets can lead to a state of ketosis, in which the concentration of blood ketones (acetoacetate, 3-beta-hydroxybutyrate, and acetone) increases as a result of increased fatty acid breakdown and activity of ketogenic enzymes. A potential concern of these ketogenic diets, as with other weight-loss diets, is the potential loss of fat-free mass (e.g., skeletal muscle). On examination of the literature, the majority of studies report decreases in fat-free mass in individuals following a ketogenic diet. However, some confounding factors exist, such as the use of aggressive weight-loss diets and potential concerns with fat free mass measurement. A limited number of studies have examined combining resistance training with ketogenic diets, and further research is needed to determine whether resistance training can effectively slow or stop the loss of fat-free mass typically seen in individuals following a ketogenic diet. Mechanisms underlying the effects of a ketogenic diet on fat-free mass and the results of implementing exercise interventions in combination with this diet should also be examined. PMID- 26284292 TI - One-Pot Synthesis of beta,beta-Disubstituted alpha,beta-Unsaturated Carbonyl Compounds. AB - TiCl4-promoted aldol reaction of ketones as aldol acceptors followed by elimination of the titanoxy group from the Ti-aldolates affords beta,beta disubstituted alpha,beta-unsaturated carbonyl compounds in a one-pot procedure. The use of additives, such as DMF, N,N,N',N'-tetramethylethylenediamine, and pyridine, in the elimination step was found to be important. PMID- 26284293 TI - Evaluation of Macular Function Using Pattern Electroretinogram in Idiopathic Epiretinal Membrane. AB - PURPOSE: Pattern electroretinogram (PERG) in idiopathic epiretinal membrane (ERM) was investigated to find the correlation of the ganglion cell function with postoperative visual acuity. DESIGN: This was a retrospective consecutive chart review. METHODS: Medical records of 24 eyes that underwent vitrectomy and membrane peeling for idiopathic ERM were reviewed retrospectively. The amplitude and implicit time of P50 and N95 in preoperative PERG were analyzed to find correlation with visual acuity and foveal thickness. The ratio of the parameters in involved eyes to those in healthy fellow eyes was calculated for analysis. RESULTS: Visual acuity (logarithm of the minimum angle of resolution) improved from 0.53 at baseline to 0.34 at 6 months (P = 0.003). Foveal thickness decreased significantly from 488.3 MUm at baseline to 374.7 MUm (P = 0.001). The preoperative N95 amplitude ratio was significantly correlated with visual acuity at 6 months after ERM removal (r = -0.423, P = 0.040), whereas the amplitude of P50 and implicit time of both waves showed no significant correlation with postoperative visual acuity. The implicit time ratio of P50 (r = 0.530, P = 0.008) and N95 (r = 0.436, P = 0.033) showed significant correlation with preoperative foveal thickness on optical coherence tomography. CONCLUSIONS: N95 amplitude in PERG was a predictor of visual outcomes after ERM surgery. These results suggest the correlation of postoperative visual acuity with the function of the ganglion cell layer, which is the closest cell layer to be affected by ERM. PMID- 26284294 TI - Maternal High-fat Diet Accelerates Development of Crohn's Disease-like Ileitis in TNFDeltaARE/WT Offspring. AB - BACKGROUND: Maternal high-fat diet (HFD) and obesity increases the risk of the offspring to develop inflammatory processes in various organs including the gut. We hypothesized that maternal diet-induced obesity programs the fetal gut towards inflammation in a mouse model of genetically-driven Crohn's disease (CD)-like ileitis. METHODS: TNF(WT/WT) and TNF(DeltaARE/WT) dams were fed an experimental control diet (CTRLD; 13 kJ% fat) or HFD (48 kJ%). Offspring mice were fed CTRLD or HFD at 4 weeks of age. Metabolic characteristics and severity of CD-like ileitis was assessed in 8- and 12-week old WT and ARE offspring measuring tissue histopathology and markers of inflammation in the distal ileum as well as plasma cytokine and LPS levels. To study prenatal effects, we laser microdissected fetal intestinal epithelial cells at 17.5 days postconception and performed microarray based global gene expression analysis. RESULTS: Maternal HFD significantly accelerated the severity of CD-like ileitis in HFD-fed ARE mice at early life stages associated with increased mucosal neutrophil infiltration, Il12p40 expression, and portal vein LPS levels. In contrast to WT mice, metabolic characteristics of ARE offspring were not affected by maternal HFD. Gene expression patterns in fetal intestinal epithelial cells of ARE mice remained largely unchanged under conditions of maternal diet-induced obesity suggesting that the positive association of intestinal inflammation, portal vein endotoxemia, and plasma TNF levels is independent of prenatal conditioning of the gut epithelium. CONCLUSIONS: Maternal HFD promotes the early onset of severe CD like ileitis in genetically susceptible offspring independent of metabolic alterations. PMID- 26284295 TI - Retained Capsule Endoscopy in a Large Tertiary Care Academic Practice and Radiologic Predictors of Retention. AB - BACKGROUND: Capsule retention reported rates range between 1% and 13%. This study aims to determine the incidence of, risk factors for, and clinical outcomes of capsule retention in a large heterogenous cohort of patients and define cross sectional imaging findings predictive of capsule retention. METHODS: A retrospective review of all capsule endoscopy (CE) examinations performed at our center from January 2002 to January 2013 was undertaken. Data on patient demographics, CE indication, findings, and details of management were analyzed. Radiologic images of patients with computed tomography scan performed 6 months before CE for patients with CE retention and for controls without CE retention but at high risk based on clinical computed tomography reports were examined by a gastrointestinal radiologist, blinded to history, and classified as worrisome based on the presence of stricture, partial obstruction, or small bowel (SB) anastomosis. RESULTS: Seventeen CE retentions (0.3%) occurred in 15 patients. Obscure gastrointestinal bleeding (47%) was the most common indication. Outcomes included surgical intervention (n = 10), endoscopic retrieval (n = 2), passing of capsule after treatment of inflammation (n = 3), passage after conservative measures for SB obstruction (n = 1), and loss to follow-up (n = 1). Patients with CE retention were more likely to have SB anastomoses (88% versus 23%) and partial obstruction (63% versus 38%) than patients with high-risk features for capsule retention who passed the capsule. CONCLUSIONS: In a tertiary care population without obstructive symptoms, capsule retention occurred in only 0.3% of cases. Review of surgical history and prior imaging for obstruction or SB anastomoses may help to reduce retention. PMID- 26284296 TI - An Optimized Anti-infliximab Bridging Enzyme-linked Immunosorbent Assay for Harmonization of Anti-infliximab Antibody Titers in Patients with Inflammatory Bowel Diseases. AB - BACKGROUND: The formation of anti-infliximab antibodies (ATI) is associated with loss of response and adverse events in patients with inflammatory bowel diseases, leading to the introduction of ATI monitoring for guiding treatment adjustments. However, a lack of standardization among current available assays exists, hampering comparison of results from different studies. This study aimed to improve the harmonization of clinically validated ATI enzyme-linked immunosorbent assays (ELISAs) by introducing a monoclonal anti-infliximab antibody (MA-IFX). METHODS: A panel of MA-IFX was evaluated as calibrator in the first generation ATI ELISA. After selection of 1 MA-IFX, assay conditions were optimized and biotin-streptavidin-enhanced detection of bound infliximab was introduced. The novel second generation ELISA was used for reanalysis of 127 serum samples from a cohort of 12 patients with inflammatory bowel disease, previously identified as ATI positive. RESULTS: Of 55 MA-IFX, MA-IFX10F9 was selected as calibrator in the ATI ELISA. After optimization of the assay conditions, a 4-fold improvement in sensitivity was obtained. Reanalysis of 127 serum samples revealed that in 5 of 12 patients (46%), ATI were detected at least 1 time point earlier with the second generation ELISA compared with the first generation ELISA. In 1 patient, the second generation ELISA allowed to detect ATI before the reinitiation of IFX after a drug holiday. CONCLUSIONS: In addition to the improved sensitivity and specificity of the second generation ATI ELISA, MA-IFX10F9 can serve as a universal calibrator to achieve assay harmonization. Moreover, the superiority of the second generation assay in analyzing serum of restarters was demonstrated. PMID- 26284297 TI - The Role of Therapeutic Drug Monitoring of Anti-Tumor Necrosis Factor Alpha Agents in Children and Adolescents with Inflammatory Bowel Disease. AB - BACKGROUND: Anti-tumor necrosis factor alpha (TNFalpha) therapy is effective in pediatric patients with inflammatory bowel disease (IBD) but associated with a risk of developing anti-drug antibodies (ADA) which lower the efficacy. Incorporating measurement of trough levels and ADA (therapeutic drug monitoring) may prevent the development of neutralizing ADA or could contribute to more optimal treatment strategies if ADA are already formed. The aim of this review was to investigate the role of therapeutic drug monitoring in children and adolescents with IBD exposed to anti-TNFalpha agents. METHODS: A literature search identified publications that measured anti-TNFalpha drug trough levels and/or ADA in children or adolescents with IBD. Studies were eligible when (1) article was written in English, (2) original data were available, (3) full text article or abstract was available, (4) measurement of antibodies against anti TNFalpha drugs or trough level of anti-TNFalpha drugs were reported, and (5) levels were measured in pediatric patients with IBD. RESULTS: The search yielded 811 articles, of which 795 articles were excluded based on title or abstract. A total of 14 studies were included in the review. CONCLUSIONS: Therapeutic drug monitoring within the pediatric IBD population certainly has a potential benefit. As occurrence of immune reactions to anti-TNFalpha agents varies widely, incorporating measurement of IFX trough levels at week 8 or week 14 predicts therapy response and allows for dose adjustments to reach therapeutic drug concentrations. However, a clinically relevant cutoff level for ADA has not been defined yet, and the optimal intervention strategy still has to be determined. PMID- 26284298 TI - Endoscopic Therapy in Crohn's Disease: Principle, Preparation, and Technique. AB - Stricture and fistula are common complications of Crohn's disease. Endoscopic balloon dilation and needle-knife stricturotomy has become a valid treatment option for Crohn's disease-associated strictures. Endoscopic therapy is also increasingly used in Crohn's disease-associated fistula. Preprocedural preparations, including routine laboratory testing, imaging examination, anticoagulant management, bowel cleansing and proper sedation, are essential to ensure a successful and safe endoscopic therapy. Adverse events, such as perforation and excessive bleeding, may occur during endoscopic intervention. The endoscopist should be well trained, always be cautious, anticipate for possible procedure-associated complications, be prepared for damage control during endoscopy, and have surgical backup ready. In this review, we discuss the principle, preparation, techniques of endoscopic therapy, as well as the prevention and management of endoscopic procedure-associated complications. We propose that inflammatory bowel disease endoscopy may be a part of training for "super" gastroenterology fellows, i.e., those seeking a career in advanced endoscopy or in inflammatory bowel disease. PMID- 26284299 TI - Effect of increased intake of fish and mussels on exposure to toxic trace elements in a healthy, middle-aged population. AB - Fish and shellfish are rich in essential nutrients, but are also a source of exposure to environmental contaminants. We aimed to investigate the effect of increased fish and mussel intake on mercury, arsenic, lead and cadmium blood concentrations. We randomly assigned 102 healthy men and women (all non-smokers) aged 48-76 years to an intervention group (n = 51) or a control group (n = 51). Intervention participants received a high amount of fish and mussels for 26 weeks (1 kg week(-1)). Controls received no intervention and were expected to eat less than 300 g of fish and mussels per week. Whole-blood concentrations of mercury, arsenic, lead and cadmium were determined using inductively coupled plasma-mass spectrometry. All available observations were included in linear multiple regression analysis to evaluate the effect of the intervention. The difference in mean change for intervention compared with control persons was 5.1 ng ml(-1) (95% confidence interval (CI) = 4.4, 5.8) for mercury, 7.1 ng ml(-1) (95% CI = 5.0, 9.2) for arsenic, and 2.6 ng ml(-1) (95% CI = 0.0, 5.2) for lead. For cadmium, the majority (65%) of the measured concentrations were below the limit of detection of 0.4 ng ml(-1), and the results are therefore not presented. In conclusion, whole-blood concentrations of mercury, arsenic and lead were significantly increased after 26 weeks intervention in this healthy, middle-aged population. The concentrations were not of health concern in this population, except for lead. For lead both the baseline and the post-intervention concentrations were high and exceeded the tolerable concentration levels. PMID- 26284301 TI - MIRMAID: A Content Management System for Medical Image Analysis Research. AB - Today, a typical clinical study can involve thousands of participants, with imaging data acquired over several time points across multiple institutions. The additional associated information (metadata) accompanying these data can cause data management to be a study-hindering bottleneck. Consistent data management is crucial for large-scale modern clinical imaging research studies. If the study is to be used for regulatory submissions, such systems must be able to meet regulatory compliance requirements for systems that manage clinical image trials, including protecting patient privacy. Our aim was to develop a system to address these needs by leveraging the capabilities of an open-source content management system (CMS) that has a highly configurable workflow; has a single interface that can store, manage, and retrieve imaging-based studies; and can handle the requirement for data auditing and project management. We developed a Web accessible CMS for medical images called Medical Imaging Research Management and Associated Information Database (MIRMAID). From its inception, MIRMAID was developed to be highly flexible and to meet the needs of diverse studies. It fulfills the need for a complete system for medical imaging research management. PMID- 26284300 TI - Directing cell therapy to anatomic target sites in vivo with magnetic resonance targeting. AB - Cell-based therapy exploits modified human cells to treat diseases but its targeted application in specific tissues, particularly those lying deep in the body where direct injection is not possible, has been problematic. Here we use a magnetic resonance imaging (MRI) system to direct macrophages carrying an oncolytic virus, Seprehvir, into primary and metastatic tumour sites in mice. To achieve this, we magnetically label macrophages with super-paramagnetic iron oxide nanoparticles and apply pulsed magnetic field gradients in the direction of the tumour sites. Magnetic resonance targeting guides macrophages from the bloodstream into tumours, resulting in increased tumour macrophage infiltration and reduction in tumour burden and metastasis. Our study indicates that clinical MRI scanners can not only track the location of magnetically labelled cells but also have the potential to steer them into one or more target tissues. PMID- 26284302 TI - Urinary Bladder Paraganglioma: AIRP Best Cases in Radiologic-Pathologic Correlation. PMID- 26284303 TI - Normal Anatomy and Compression Areas of Nerves of the Foot and Ankle: US and MR Imaging with Anatomic Correlation. AB - The anatomy of the nerves of the foot and ankle is complex, and familiarity with the normal anatomy and course of these nerves as well as common anatomic variants is essential for correct identification at imaging. Ultrasonography (US) and magnetic resonance (MR) imaging allow visualization of these nerves and may facilitate diagnosis of various compression syndromes, such as "jogger's heel," Baxter neuropathy, and Morton neuroma. It may be difficult to distinguish the nerves from adjacent vasculature at MR imaging, and US can help in differentiation. The authors review the normal anatomy and common variants of the nerves of the foot and ankle, with use of dissected specimens and correlative US and MR imaging findings. In addition, the authors illustrate proper probe positioning, which is essential for visualizing the nerves at US. The authors' discussion focuses on the superficial and deep peroneal, sural, saphenous, tibial, medial and lateral plantar, medial and inferior calcaneal, common digital, and medial proper plantar digital nerves. PMID- 26284304 TI - Prevalence of Food Addiction Among Low-Income Reproductive-Aged Women. AB - BACKGROUND: Hyperpalatable foods (i.e., high in salt, sugar, or fat) have been shown to have addictive properties that may contribute to overeating. Prior studies conducted on food addiction behaviors are mostly based on white and middle-aged women. Data are not available, however, on reproductive-aged women from other races/ethnicities or low-income women. The purpose of this study was to examine the prevalence and correlates of food addiction among multiethnic women of low socioeconomic status. METHODS: We conducted a cross-sectional survey of health behaviors, including food addiction according to the Yale Food Addiction Scale (YFAS) between July 2010 and February 2011 among 18- to 40-year old low-income women attending reproductive-health clinics (N = 1,067). RESULTS: Overall, 2.8% of women surveyed met the diagnosis of food addiction. The prevalence of food addiction did not differ by age group, race/ethnicity, education, income, or body mass index categories, tobacco and alcohol use, or physical activity. However, it did differ by level of depression (p < 0.01). The YFAS symptom count score significantly differed by race/ethnicity (p < 0.01) with black women having higher scores than Hispanic women. Racial differences were also observed among some of the YFAS symptoms. CONCLUSION: These findings demonstrated a low prevalence of food addiction among low-income, reproductive aged women. Racial differences were observed in the YFAS symptom count score, but not in the overall prevalence of food addition. Additionally, women with food addiction had higher levels of depression than women without food addiction. PMID- 26284305 TI - High-Performance GaAs Nanowire Solar Cells for Flexible and Transparent Photovoltaics. AB - Among many available photovoltaic technologies at present, gallium arsenide (GaAs) is one of the recognized leaders for performance and reliability; however, it is still a great challenge to achieve cost-effective GaAs solar cells for smart systems such as transparent and flexible photovoltaics. In this study, highly crystalline long GaAs nanowires (NWs) with minimal crystal defects are synthesized economically by chemical vapor deposition and configured into novel Schottky photovoltaic structures by simply using asymmetric Au-Al contacts. Without any doping profiles such as p-n junction and complicated coaxial junction structures, the single NW Schottky device shows a record high apparent energy conversion efficiency of 16% under air mass 1.5 global illumination by normalizing to the projection area of the NW. The corresponding photovoltaic output can be further enhanced by connecting individual cells in series and in parallel as well as by fabricating NW array solar cells via contact printing showing an overall efficiency of 1.6%. Importantly, these Schottky cells can be easily integrated on the glass and plastic substrates for transparent and flexible photovoltaics, which explicitly demonstrate the outstanding versatility and promising perspective of these GaAs NW Schottky photovoltaics for next generation smart solar energy harvesting devices. PMID- 26284307 TI - HLA haploidentical peripheral blood stem cell transplantation using reduced dose of posttransplantation cyclophosphamide for poor-prognosis or refractory leukemia and myelodysplastic syndrome. AB - Nonmyeloablative, human leukocyte antigen (HLA) haploidentical, T-cell-replete bone marrow transplantation followed by high-dose posttransplantation cyclophosphamide (PT/Cy) has recently been developed. This transplantation milieu has resulted in favorable outcomes with low transplantation-related mortality, owing to a low incidence of graft-versus-host disease (GVHD), without increased infectious complications. However, the high relapse rate remains a major concern. We therefore performed a prospective pilot study of HLA haploidentical peripheral blood stem cell transplantation (PBSCT) with intensified conditioning, followed by two lower doses of PT/Cy. A total of 20 patients with refractory or poor prognosis myelodysplastic syndrome (MDS) and leukemia were enrolled in the study. A trend toward a lower incidence of grade III-IV acute GVHD at day 100 in the group receiving 25 mg/kg * 2 doses of PT/Cy, compared with the group receiving 25 mg/kg of PT/Cy (9.1% vs. 33%, p = 0.20), was noted. However, the cumulative incidence of chronic GVHD was low, at 10% irrespective of PT/Cy dose. The number of infused CD34(+) cells significantly correlated with the grade of acute GVHD (p = 0.004). In addition, the occurrence of BK virus hemorrhagic cystitis was significantly more common in the double-dose PT/Cy group (25% vs. 0%, p = 0.043), especially when combined with busulfan. The probability of overall survival at 1 year in the double-dose group tended to be better compared with that in the single-dose group (64% vs. 44%, respectively; p = 0.20). In conclusion, HLA haploidentical, T-cell-replete PBSCT with 25 mg/kg * 2 doses of PT/Cy might be a feasible option for treating high-risk leukemia and MDS. PMID- 26284306 TI - The Antipancreatic Cancer Activity of OSI-027, a Potent and Selective Inhibitor of mTORC1 and mTORC2. AB - In the present study, we investigated the potential activity of OSI-027, a potent and selective mammalian target of rapamycin (mTOR) complex 1/2 (mTORC1/2) dual inhibitor, against pancreatic cancer cells both in vitro and in vivo. We demonstrated that OSI-027 inhibited survival and growth of both primary and transformed (PANC-1 and MIA PaCa-2 lines) human pancreatic cancer cells. Meanwhile, OSI-027 induced caspase-dependent apoptotic death of the pancreatic cancer cells. On the other hand, caspase inhibitors alleviated cytotoxicity by OSI-027. At the molecular level, OSI-027 treatment blocked mTORC1 and mTORC2 activation simultaneously, without affecting ERK-mitogen-activated protein kinase activation. Importantly, OSI-027 activated cytoprotective autophagy in the above cancer cells. Whereas pharmacological blockage of autophagy or siRNA knockdown of Beclin-1 significantly enhanced the OSI-027-induced activity against pancreatic cancer cells. Specifically, a relatively low dose of OSI-027 sensitized gemcitabine-induced pancreatic cancer cell death in vitro. Further, administration of OSI-027 or together with gemcitabine dramatically inhibited PANC-1 xenograft growth in severe combined immunodeficiency mice, leading to significant mice survival improvement. In summary, the preclinical results of this study suggest that targeting mTORC1/2 synchronously by OSI-027 could be further investigated as a valuable treatment for pancreatic cancer. PMID- 26284308 TI - Serum nitric oxide metabolites are associated with the risk of hypertriglyceridemic-waist phenotype in women: Tehran Lipid and Glucose Study. AB - BACKGROUND AND AIM: There are some controversial issues regarding the association of nitric oxide and obesity-related states. This study was conducted to investigate whether serum nitric oxide metabolites (NOx) could predict the occurrence of visceral lipid accumulation, defined as hypertriglyceridemic-waist (HTW) phenotype. METHODS: We used a prospective approach for this study conducted on participants of the Tehran Lipid and Glucose Study, 2243 adult men and women were followed for a median of 6.3 years. Serum NOx concentrations were measured at baseline (2006-2008), and demographics, anthropometrics and biochemical variables were evaluated at baseline and again after a 3-year (2009-2011) and a 6 year follow-up (2012-2014). The occurrence of HTW phenotype, defined as waist circumference >=90 cm in men and >=85 cm in women, along with serum triglyceride levels >=177 mg/dL, were assessed across serum NOx tertiles. RESULTS: Mean age of participants was 41.5 +/- 14.5 years at baseline and 39.4% were male. The cumulative incidence of HTW phenotype was 37.6% (33.2% in men, 40.5% in women). There was no significant association between serum NOx and the occurrence of HTW phenotype in men. After adjustment of confounding variables, risk of HTW phenotype in women, in the highest compared to the lowest tertile of serum NOx (>=30.9 vs. <19.9 MUmol/L), increased by 39% (OR = 1.39, 95% CI = 1.05-1.93, P for trend = 0.053). CONCLUSION: Serum NOx level was an independent predictor of HTW phenotype in women. PMID- 26284309 TI - Microarray analysis of gene expression patterns in the leaf during potato tuberization in the potato somatic hybrid Solanum tuberosum and Solanum etuberosum. AB - Genes involved in photoassimilate partitioning and changes in hormonal balance are important for potato tuberization. In the present study, we investigated gene expression patterns in the tuber-bearing potato somatic hybrid (E1-3) and control non-tuberous wild species Solanum etuberosum (Etb) by microarray. Plants were grown under controlled conditions and leaves were collected at eight tuber developmental stages for microarray analysis. A t-test analysis identified a total of 468 genes (94 up-regulated and 374 down-regulated) that were statistically significant (p <= 0.05) and differentially expressed in E1-3 and Etb. Gene Ontology (GO) characterization of the 468 genes revealed that 145 were annotated and 323 were of unknown function. Further, these 145 genes were grouped based on GO biological processes followed by molecular function and (or) PGSC description into 15 gene sets, namely (1) transport, (2) metabolic process, (3) biological process, (4) photosynthesis, (5) oxidation-reduction, (6) transcription, (7) translation, (8) binding, (9) protein phosphorylation, (10) protein folding, (11) ubiquitin-dependent protein catabolic process, (12) RNA processing, (13) negative regulation of protein, (14) methylation, and (15) mitosis. RT-PCR analysis of 10 selected highly significant genes (p <= 0.01) confirmed the microarray results. Overall, we show that candidate genes induced in leaves of E1-3 were implicated in tuberization processes such as transport, carbohydrate metabolism, phytohormones, and transcription/translation/binding functions. Hence, our results provide an insight into the candidate genes induced in leaf tissues during tuberization in E1-3. PMID- 26284310 TI - Initial investigation of a novel noninvasive weight loss therapy using MRI-Guided high intensity focused ultrasound (MR-HIFU) of visceral fat. AB - PURPOSE: MRI-guided high intensity focused ultrasound (MR-HIFU) allows noninvasive heating of deep tissues. Specifically targeting visceral fat deposits with MR-HIFU could offer an effective therapy for reversing the development of obesity, diabetes, and metabolic syndrome. METHODS: Overweight rats received either MR-HIFU of visceral fat, sham treatment, no treatment, or ex vivo temperature calibration. Conventional MR thermometry methods are not effective in fat tissue. Therefore, the T2 of fat was used to estimate heating in adipose tissue. RESULTS: HIFU treated rats lost 7.5% of their body weight 10 days after HIFU, compared with 1.9% weight loss in sham animals (P = 0.008) and 1.3% weight increase in untreated animals (P = 0.004). Additionally, the abdominal fat volume in treated animals decreased by 8.2 mL 7 days after treatment (P = 0.002). The T2 of fat at 1.5 Tesla increased by 3.3 ms per degrees C. The fat T2 was 103.3 ms before HIFU, but increased to 128.7 ms (P = 0.0005) after HIFU at 70 watts for 16 s and to 131.9 ms (P = 0.0005) after HIFU at 100 watts for 16 s. CONCLUSION: These experiments demonstrate that MR-HIFU of visceral fat could provide a safe, effective, and noninvasive weight loss therapy for combating obesity and the subsequent medical complications. Magn Reson Med 76:282-289, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26284311 TI - Airway resistance and allergic sensitization in children with obstructive sleep apnea hypopnea syndrome. AB - OBJECTIVE: The purpose of this study was to determine the airway resistance in Chinese children with obstructive sleep apnea hypopnea syndrome (OSAHS) by impulse oscilloetry (IOS) and investigate the association of the severity of OSAHS with the airway resistance and allergic sensitization. METHOD: A total of 120 children (92 boys) treated for snoring in Beijing Children's Hospital between October 2010 and March 2011 were included in this study. Ninety-three children were diagnosed with OSAHS and 27 did not show OSAHS. Total airway resistance (R5), proximal airway resistance (R20), and peripheral airway resistance (X5) were determined by IOS. Serum levels of total IgE and allergen-specific IgE (sIgE) were also determined. RESULTS: R5 in the OSAHS group was significantly higher than that in the non-OSAHS group (P = 0.0025), whereas R20 and X5 were similar in the two groups. R5 was positively correlated with apnea hypopnea index and obstructive apnea index and negatively correlated with the lowest arterial oxygen saturation significantly (all P < 0.05). The percentage of children with abnormal serum levels of total IgE or abnormal allergen-specific IgEs was comparable in OSAHS and non-OSAHS groups. The proportions of abnormal R5 and of abnormal serum levels of total IgE were significantly higher in children with severe OSAHS compared with children with mild or moderate OSAHS (all P < 0.05). CONCLUSIONS: Total airway resistance was significantly increased in Children with OSAHS. Allergic sensitization might contribute to the exacerbation of existing OSAHS in children. Large scale studies are required to further validate these findings. PMID- 26284312 TI - Regulatory oversight in the United States of vascularized composite allografts. AB - Vascularized composite allograft (VCA) transplantation is a medically acceptable treatment for the reconstruction of major tissue loss. The advent of VCA transplantation has spurred regulatory and policy development in the United States to address the multiple clinical, ethical and legal issues that must be considered for the practice of VCA donation and transplantation to develop within the existing framework of public trust and transparency vital to the success of donation and transplantation. PMID- 26284313 TI - Optimization and characterization of injectable chitosan-iodixanol-based hydrogels for the embolization of blood vessels. AB - Chitosan-thermosensitive hydrogels present interesting features for the embolization of blood vessels, but need to be better characterized and optimized. Chitosan polymer (degree of deacetylation (DDA) of 94%) was purified and combined with Visipaque (VIS), a nonionic isotonic contrast agent composed of iodixanol. A beta-glycerolphosphate (betaGP) solution was then added to induce gelation at body temperature. The gelation process was monitored by rheometry, measuring the evolution of the sample storage (G') and loss (G") moduli as a function of VIS and betaGP concentration. Adding VIS significantly slowed down gelation kinetics, but a 12% and higher betaGP concentration provided a radiopaque solution, which at 37 degrees C, gels immediately. A custom-made in vitro embolization bench test was developed to assess the gel's occlusive properties, and its injectability through a small diameter catheter was verified. Results show that the short-term occlusive properties of the gel were insufficient when using a betaGP concentration of 12% w/v (about 0.4M), but that increasing the betaGP to 20% (0.6M) allowed an acceleration of the gelation and the immediate blocking of flow above physiological pressure. The contrast agent was rapidly released in solution, such that it would not interfere with future follow-up imaging. In accordance with the literature data, the cytotoxicity of gel extracts increased with betaGP concentration and to a lesser extent with VIS concentration. Preliminary in vivo testing showed easy injection by catheter and good visibility under fluoroscopy. These results suggest that radiopaque CH/betaGP20%/VIS hydrogels present significant potential as embolizing agents for blood vessels and aneurysms. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1551-1562, 2016. PMID- 26284314 TI - Physical Activity and Variation in Momentary Behavioral Cognitions: An Ecological Momentary Assessment Study. AB - BACKGROUND: Decisions to perform moderate-to-vigorous physical activity (MVPA) involve behavioral cognitive processes that may differ within individuals depending on the situation. METHODS: Ecological momentary assessment (EMA) was used to examine the relationships of momentary behavioral cognitions (ie, self efficacy, outcome expectancy, intentions) with MVPA (measured by accelerometer). A sample of 116 adults (mean age, 40.3 years; 72.4% female) provided real-time EMA responses via mobile phones across 4 days. Multilevel models were used to test whether momentary behavioral cognitions differed across contexts and were associated with subsequent MVPA. Mixed-effects location scale models were used to examine whether subject-level means and within-subjects variances in behavioral cognitions were associated with average daily MVPA. RESULTS: Momentary behavioral cognitions differed across contexts for self-efficacy (P = .007) but not for outcome expectancy (P = .53) or intentions (P = .16). Momentary self-efficacy, intentions, and their interaction predicted MVPA within the subsequent 2 hours (Ps < .01). Average daily MVPA was positively associated with within-subjects variance in momentary self-efficacy and intentions for physical activity (Ps < .05). CONCLUSIONS: Although momentary behavioral cognitions are related to subsequent MVPA, adults with higher average MVPA have more variation in physical activity self-efficacy and intentions. Performing MVPA may depend more on how much behavioral cognitions vary across the day than whether they are generally high or low. PMID- 26284315 TI - Application of liquid chromatographic/tandem mass spectrometric method to a urinary excretion study of subutinib and active metabolite in human urine. AB - A novel and selective liquid chromatographic-mass spectrometric method (LC-MS/MS) has been established and validated for simultaneous determination of subutinib and active metabolite in human urine. Urine samples were extracted by liquid liquid extraction with ethyl acetate and separated on a Wondasil C18 (150 * 2.1 mm, 3.5 um), with methanol-0.2% formic acid solution (73:27, v/v) as mobile phase at flow rate of 0.2 mL/min. The linear range was 0.5000-200.0 ng/mL for subutinib and active metabolite, with a lower limit of quantitation of 0.5000 ng/mL. Intra- and inter-run precisions were all <11.8 and 14.3%, and the accuracies were all <4.5 and 5.4%, with the extraction recoveries 88.8-97.5 and 93.8-99.4% for the two analytes, respectively. The carryover values were all <15% for the two anayltes. The method was successfully applied to study urinary excretion of subutinib and active metabolite in human after oral administration of subutinib maleate capsules in fed and fasting states. PMID- 26284316 TI - Aggregation-induced emission behavior of a pH-controlled molecular shuttle based on a tetraphenylethene moiety. AB - Tetraphenylethene (TPE) with aggregation-induced emission (AIE) behavior as a popular backbone is applied widely in the construction of functional supramolecular systems. In this work, a TPE-based linear molecule having amide and amine units is synthesized. Its ammonium template is used to construct the N hetero crown ether-based [2]rotaxane by the template-directed clipping approach. Their structures are well-characterized by NMR, MALDI-TOF-MS and elemental analysis. Owing to the existence of the amide unit, [2]rotaxane possesses the function of a molecular shuttle. The shuttling motion of the macrocycle component between the ammonium station and the amide station can be driven by external acid base stimuli in solution, accompanied by changes in visual behavior. Investigation on their AIE behavior shows that (1) ammonium reaches the aggregation state almost in the presence of same water with the deprotonated form of ammonium; (2) the [2]rotaxane that the macrocycle component locates at the site of ammonium forms the aggregation state in the presence of less water than the deprotonated [2]rotaxane that the macrocycle component locates at the site of the amide, attributed to stronger interaction between the crown ether component and the TPE unit of the template component when the distance between the two is shorter. The result indicates that the shuttling motion of the macrocycle component can adjust the aggregation state of AIE molecules. PMID- 26284317 TI - Antiseptic solutions modulate the paracrine-like activity of bone chips: differential impact of chlorhexidine and sodium hypochlorite. AB - AIM: Chemical decontamination increases the availability of bone grafts; however, it remains unclear whether antiseptic processing changes the biological activity of bone. MATERIALS AND METHODS: Bone chips were incubated with four different antiseptic solutions including (1) povidone-iodine (0.5%), (2) chlorhexidine diguluconate (0.2%), (3) hydrogen peroxide (1%) and (4) sodium hypochlorite (0.25%). After 10 min. of incubation, changes in the capacity of the bone conditioned medium (BCM) to modulate gene expression of gingival fibroblasts was investigated. RESULTS: Conditioned medium obtained from freshly prepared bone chips increased the expression of TGF-beta target genes interleukin 11 (IL11), proteoglycan4 (PRG4), NADPH oxidase 4 (NOX4), and decreased the expression of adrenomedullin (ADM), and pentraxin 3 (PTX3) in gingival fibroblasts. Incubation of bone chips with 0.2% chlorhexidine, followed by vigorously washing resulted in a BCM with even higher expression of IL11, PRG4 and NOX4. These findings were also detected with a decrease in cell viability and an activation of apoptosis signalling. Chlorhexidine alone, at low concentrations, increased IL11, PRG4 and NOX4 expression, independent of the TGF-beta receptor I kinase activity. In contrast, 0.25% sodium hypochlorite almost entirely abolished the activity of BCM, whereas the other two antiseptic solutions, 1% hydrogen peroxide and 0.5% povidone-iodine, had relatively no impact respectively. CONCLUSION: These in vitro findings demonstrate that incubation of bone chips with chlorhexidine differentially affects the activity of the respective BCM compared to the other antiseptic solutions. The data further suggest that the main effects are caused by chlorhexidine remaining in the BCM after repeated washing of the bone chips. PMID- 26284318 TI - Stable Four-Coordinate Guanidinatosilicon(IV) Complexes with SiN3El Skeletons (El = S, Se, Te) and Si=El Double Bonds. AB - To get information about the reactivity profile of the donor-stabilized guanidinatosilicon(II) complexes 2 and 3, a series of oxidative addition reactions was studied. Treatment of 2 and 3 with S8, Se, or Te afforded the respective four-coordinate silicon(IV) complexes 8-10 and 12-14, which contain an SiN3 El skeleton (El = S, Se, Te) with an Si=El double bond. Treatment of 2 with N2O yielded the dinuclear four-coordinate silicon(IV) complex 11 with an SiN3O skeleton and a central four-membered Si2O2 ring. Compounds 8-14 exist both in the solid state and in solution. They were characterized by elemental analyses, NMR spectroscopic studies in the solid state and in solution, and crystal structure analyses. The reactivity profile of 2 was compared with that of the structurally related bis[N,N'-diisopropylbenzamidinato(-)]silicon(II) (1), which is three coordinate in the solid state and four-coordinate in solution (1'). In contrast, as shown by state-of-the-art relativistic DFT analyses and experimental studies, silylene 2 is three-coordinate both in the solid state and solution. The three coordinate species 2 is 9.3 kcal mol(-1) more stable in benzene than the four coordinate isomer 2'. The reason for this was studied by bonding analyses of 2 and 2', which were compared with those of 1 and 1'. The gas-phase proton affinities of the relevant species in solution (1' and 2) amount to 288.8 and 273.8 kcal mol(-1), respectively. PMID- 26284319 TI - Clinical and molecular characterization of seven Egyptian families with autosomal recessive robinow syndrome: Identification of four novel ROR2 gene mutations. AB - Robinow syndrome (RS) is a rare genetic disorder characterized by limb shortening, genital hypoplasia, and craniofacial/orodental abnormalities. The syndrome follows both autosomal dominant and recessive patterns of inheritance with similar phenotypic presentation and overlapping features. Autosomal recessive Robinow syndrome (ARRS) is caused by mutations in the ROR2 gene. Here, we present the clinical, radiological and molecular findings of 11 Egyptian patients from 7 unrelated consanguineous families with clinical features of ARRS. Mutation analyses of ROR2 gene identified five pathogenic mutations distributed all over the gene. The identified mutations included four novel (G326A, D166H, S677F, and R528Q) and one previously reported (Y192D). Our results extend the number of ROR2 mutations identified so far, suggest a founder effect in the Egyptian population, and emphasize the important role of genetic testing in proper counseling and patients' management. PMID- 26284321 TI - Determination of three kinds of banned drugs in milk powder by hybrid solid-phase extraction purification combined with gas chromatography and mass spectrometry. AB - A gradient clean-up method for the quantification of five kinds of banned drugs (two hormones, two sedatives, and one chloramphenicol) in milk powder was developed. We used the combination of solid-phase extraction purification with gas chromatography and mass spectrometry. Milk powder was initially hydrolyzed by beta-glucuronidase/arylsulfatase, and then the hydrolyzed solution was concentrated and purified using a C8 and cation resin solid-phase extraction column. To isolate hormones and chloramphenicol drugs, products from the previous step were diluted with methanol and further purified using a silica and diatomite solid-phase extraction column. After derivatization, the drugs were analyzed by gas chromatography with mass spectrometry, and the hydrolyzed solution was diluted with 5% ammoniated methanol to purify sedatives before gas chromatography with mass spectrometry analysis. Results showed that after adding the banned drugs at concentrations of 0.3-10.0 MUg/kg, the average recovery range was 78.2 97.3% with relative standard deviations of 5.3-12.5%. The limit of quantification of the banned drugs (S/N >= 10) was 0.3-5.0 MUg/kg, whereas the limit of detection (S/N >= 3) was 0.1-2.0 MUg/kg. The solid-phase extraction gradient purification system was simple, rapid, and accurate, and could satisfy the detection requirements of hormone, sedatives, and chloramphenicol drugs when used together with gas chromatography and mass spectrometry. PMID- 26284322 TI - [Not Available]. PMID- 26284320 TI - Genome-wide variant by serum urate interaction in Parkinson's disease. AB - OBJECTIVE: Serum urate levels have been associated with risk for and progression of Parkinson's disease (PD). Urate-related compounds are therapeutic candidates in neuroprotective efforts to slow PD progression. A urate-elevating agent is currently under investigation as a potential disease-modifying strategy in people with PD. However, PD is a heterogeneous disorder, and genetic variation may explain divergence in disease severity and progression. METHODS: We conducted a genome-wide association study to identify gene variant * serum urate interaction effects on the striatal (123) I-ioflupane (DaTscan) binding ratio measured using single photon emission computed tomography in patients with possible PD from the Parkinson's Progression Markers Initiative (PPMI, n = 360). Follow-up analyses were conducted to assess gene variant * serum urate interaction effects on magnetic resonance imaging-derived regional brain volumes and clinical status. We then attempted to replicate our primary analysis in patients who entered the Parkinson Research Examination of CEP-1347 Trial (PRECEPT) with a clinical diagnosis of PD (n = 349). RESULTS: Rs1109303 (T>G) variant within the INPP5K gene on chromosome 17p13.3 demonstrated a genome-wide significant interaction with serum urate level to predict striatal dopamine transporter density among all PPMI participants (n = 359) with possible PD (p = 2.01 * 10(-8) ; after excluding participants with SWEDD [scan without evidence of dopaminergic deficit]: p = 1.12 * 10(-9) ; n = 316). Independent of striatal dopamine transporter density, similar effects on brain atrophy, bradykinesia, anxiety, and depression were observed. No effect was present in the PRECEPT sample at baseline; however, in non-SWEDD PD participants in PRECEPT (n = 309), we observed a significant longitudinal genotype * serum urate interaction effect, consistent in direction with the PPMI sample, on progression of striatal dopamine transporter density over the 22-month follow-up. INTERPRETATION: Genetic profile combined with serum urate level can be used to predict disease severity and potential disease progression in patients with PD. These results may be relevant to therapeutic efforts targeting the urate pathway. PMID- 26284323 TI - [Gender-specific aspects in visceral medicine]. PMID- 26284324 TI - [Gender differences and inflammatory bowel disease]. AB - This review focuses on the gender and sex dimorphic disease profile and treatment reality of patients suffering from inflammatory bowel diseases (IBD). It provides an overview of gender-specific differences in the disease course, medical and surgical therapy as well as psychosocial aspects of IBD. PMID- 26284325 TI - [Gastro-esophageal Reflux Disease and malignant progression--equal risk for men and women?]. AB - Gastroesophageal reflux disease (GERD) is highly prevalent in the Western world. Patients with GERD have a 10 fold increased risk to develop a Barrett's esophagus. Patients with Barrett's esophagus have a higher risk for an esophageal adenocarcinoma. Men have more severe reflux with a higher grade of inflammation and acid reflux. This seems to be the reason why men develop a Barrett's esophagus more frequently--the risk is approximately 2 to 3 fold and the risk for an esophageal adenocarcinoma is even 3 to 6 times higher. PMID- 26284326 TI - [Clinically relevant, gender-specific differences in colorectal carcinoma (CRC)]. AB - The incidence of colorectal cancer worldwide is higher in men. Risk factors like smoking, overweight, or dietary exposures cannot explain this gender difference. In the pathogenesis of colorectal carcinoma, estrogen seems to play an important protective role. Estrogen may reduce the risk of developing colon cancer in premenopausal women. The expression of estrogen receptor beta in healthy colon is significantly decreased in the development of colon cancer. The role of estrogen in pathogenic pathways is most likely protective or might serve as a tumor suppressor. However, the exact role of estrogen in the carcinogenesis of colorectal cancer still remains unclear. Furthermore, tumor localization depends on age and gender. Therefore, in postmenopausal women there is a shift to predominantly right-sided cancers. Here, a link between tumor localization and MSI-H (microsatellite-high) status can be assumed. There are virtually no prospective randomised trials in adjuvant or palliative therapy of patients with colorectal cancer. Earlier data from registries point to a better post-operative survival of women, while men seem to benefit more from adjuvant therapy. Potentially, there may be a role of an increased toxicity to 5-FU in women. In the palliative setting, there are also only few gender-specific analyses. Women with right-sided colon cancers show a significant worse response and survival under an anti-EGFR antibody treatment compared with men and left-sided cancers. A focus on gender-specific differences should be incorporated more often in future randomised trials. PMID- 26284327 TI - [Gender-specific aspects of Lynch syndrome--an update]. AB - Approximately 3-5% of all colorectal cancers are based on a hereditary predisposition, of which Lynch syndrome is by far the most frequent hereditary cancer syndrome. Beside colorectal cancer Lynch-Syndrome is the most frequent predisposing hereditary cause of endometrial cancer and is also associated with gastric cancer, ovarian cancer, cancer of the urinary tract as well as several other cancers. Genetically Lynch syndrome is caused by a germline mutation in one of the so-called mismatch-repair-genes. Based on several epidemiological studies, increasingly differences in the penetrance of the different cancers occurring are associated with the affected gene and also gender of the patient have been reported. The lifetime risk of colorectal cancer for males with Lynch syndrome generally is significantly higher and the age of first manifestation significantly earlier compared to females. The difference is especially notable in men with a MSH6-mutation. Moreover, the lifetime risk for gastric, bladder, and urothelial cancer is much higher in males. Women with an MSH6 mutation have a much higher risk for endometrial (and ovarian) cancer than for colorectal cancer. In patients with Muir Torre syndrome again males are predominantly affected and almost all affected have a mutation in MSH2 rather than in any other MMR gene. This review is an update of the literature analyzing gen and gender specific aspects of Lynch syndrome. To date these associations are based on retrospective studies, that require confirmation in a prospective setting with large patient numbers in order to identify validated, individualized gene and gender screening recommendations in the future. Especially in a syndrome with multiple potential cancer targets, an intense yearly program comprising several invasive procedures has a negative effect on patient compliance. PMID- 26284329 TI - Ultrasound in radioembolization induced liver disease (REILD). AB - BACKGROUND: REILD (radioembolization-induced liver disease) is a rare complication after SIRT (selective internal radiotherapy) of the liver. The diagnosis is based on a combination of clinical signs and symptoms, laboratory values, and MRT findings. Data about sonographic signs associated with REILD are lacking. In this report, we describe sonographic changes in two female patients with REILD. CASE REPORTS: Patient 1: a 34-year-old woman with colorectal carcinoma liver metastasis. Two weeks after SIRT, the patient developed histology proven REILD. Abdominal ultrasound revealed pronounced hepatomegaly, with inhomogeneous, slightly hyperechoic parenchyma without attenuation. The well known metastasis could not be delineated easily. Liver veins were compressed, with ill defined borders, and flattened biphasic blood flow in duplex sonography. Signs of portal hypertension with ascites, and splenomegaly were present. A therapy with diuretics, heparin, steroids, and ursodesoxycholic acid was introduced, and the patient recovered. After seven weeks, the ascites had resolved, and the liver parenchyma returned to normal echogenicity. Furthermore, the metastases in both lobes were clearly visible again. The liver veins were well delineated, normal sized, with regular triphasic blood flow in duplex sonography, but splenomegaly persisted. Patient 2: a 58-year-old women with recurrent multifocal peripheral cholangiocarcioma. Abdominal ultrasound 5 weeks after SIRT revealed a slightly increased echogenicity of the liver. Liver veins showed slightly irregular borders with biphasic flow pattern. In contrast to patient no.1, liver metastases could still be delineated easily. Ascites or splenomegaly were not present. Laboratory parameters and MRT findings were consistent with a diagnosis of mild REILD. Liver biopsy was not performed. No specific therapy was introduced. Five weeks later, the liver parenchyma became more homogeneous again, and the liver veins normalized with smooth vessel borders, but still flattened biphasic flow pattern. CONCLUSION: Transient hepatomegaly, with inhomogeneous hyperechoic parenchyma without attenuation, and compressed, ill delineated liver veins, with monophasic or flattened biphasic blood flow, are typical sonographic findings in REILD. In addition, common signs of portal hypertension can be present. Liver alterations and ascites resolve parallel with clinical improvement. Splenomegaly can persist. PMID- 26284328 TI - [Catch me if you can: endoscopic remove of a needle from the jejunum]. AB - INTRODUCTION: The ingestion of foreign bodies is a frequently observed problem in daily clinical practice. In order to avoid complications such as perforation, endoscopic removal of potentially penetrating foreign bodies should be attempted quickly. The use of various endoscopic techniques has been reported for this purpose. However, extraction of foreign bodies from the mid gastrointestinal tract has rarely been reported. CASE REPORT: We present the case of a patient who had swallowed a safety needle which could safely be removed from the jejunum by means of double-balloon enteroscopy (DBE). The combination of a thin p-type enteroscope with a thick t-type overtube was used in order to improve the manoeuvrability of the endoscope. The needle was pulled into the overtube which served as a protective shield during the retrieval of the endoscope. CONCLUSION: Our case report describes the potential of removing foreign bodies from the deep small bowel by pulling them into the overtube of a double-balloon enteroscope. If the suspicion of foreign body impaction in the small bowel is made, it may be advisable to primarily choose a balloon enteroscopy system. Through this, quick and deep insertion can be combined with a safe removal of the foreign body. PMID- 26284330 TI - [S3-guidelines "sedation in gastrointestinal endoscopy" 2014 (AWMF register no. 021/014)]. PMID- 26284331 TI - [Management of Crohn's disease after intestinal resection]. PMID- 26284332 TI - Safety profile of biologic agents for Behcet's disease in a multicenter observational cohort study. AB - AIM: The primary aim of this study was to explore the safety profile of biologic treatments in Behcet's disease (BD), based on their mechanism of action; the secondary aim was to study any potential variation in terms of retention rate according to each single drug. METHOD: We studied a total of 85 treatment regimens with biologic agents from 64 patients. The total follow-up was calculated as 8640 patient-years (anti-tumor necrosis factor [TNF]-alpha 7.020, anti-interleukin [IL]-beta 1.368). Cumulative rates of drug retention were studied using the Kaplan-Meier plot and covariates in the regression model included the mechanism of action of the biologic agent, other concomitant therapies, disease duration, sex, age at start of drug therapy; for each confounding factor hazard ratios (HR) were calculated. RESULTS: The most frequently prescribed biologic treatments were anti-TNF-alpha agents (79%), while anti-IL1-beta was used in the remaining regimens. Concomitant disease-modifying antirheumatic drugs were prescribed in 36% of patients, mainly cyclosporine and methotrexate, while in 35/85 regimens low-dose glucocorticoids were associated. During the follow-up, in all but one regimen the safety profile was free of any adverse events or serious adverse events; we observed only one case of endocarditis, reported during the 10th month of etanercept. CONCLUSION: Data from a large multicenter cohort suggest that anti-TNF-alpha and anti-IL1-beta agents are characterized by an excellent safety profile in BD. PMID- 26284333 TI - Influence of mRNA expression of epiregulin and amphiregulin on outcome of patients with metastatic colorectal cancer treated with 5-FU/LV plus irinotecan or irinotecan plus oxaliplatin as first-line treatment (FIRE 1-trial). AB - Our aim was to investigate the impact of EREG and AREG mRNA expression (by RT qPCR) in patients with metastatic colorectal cancer (mCRC). In addition, epidermal growth factor receptor (EGFR) expression (by immunohistochemistry) as well as RAS-and PIK3CA-mutations (by pyrosequencing) were assessed. Tumors of 208 mCRC patients receiving 5-fluorouracil/leucovorin plus irinotecan (FUFIRI) or irinotecan plus oxaliplatin (mIROX) within the FIRE-1 trial were analyzed for mutations. Molecular characteristics were correlated with response, progression free survival (PFS), overall survival (OS). mRNA expression was evaluated using ROC-analysis in 192 tumors (AREG high n = 31 vs. low n = 161; EREG high n = 89 vs. low n = 103). High versus low AREG expression was associated with PFS of 10.0 versus 8.0 months (HR = 0.62, 95% CI: 0.402-0.940, p = 0.03) and OS of 24.6 versus 18.7 months (HR = 0.72, 95% CI: 0.476-1.078, p = 0.11). High versus low EREG expression correlated with prolonged PFS (9.4 vs. 6.8 months, HR = 0.62, 95% CI: 0.460-0.846, p = 0.002) and OS (25.8 vs. 15.5 months, HR = 0.48, 95% CI: 0.351-0.657, p < 0.001). The positive prognostic effect of high EREG expression was confirmed in a multivariate analysis and was neither affected by EGFR expression nor by mutations of RAS- and PIK3CA-genes. EREG expression appears as an independent prognostic marker in patients with mCRC receiving first-line irinotecan-based chemotherapy. PMID- 26284334 TI - ADAM10: a new player in breast cancer progression? AB - BACKGROUND: The ADAM proteases are best known for their role in shedding the extracellular domain of transmembrane proteins. Among the transmembrane proteins shed by ADAM10 are notch, HER2, E-cadherin, CD44, L1 and the EGFR ligands, EGF and betacellulin. As cleavage of several of these proteins has been implicated in cancer formation and progression, we hypothesised that ADAM10 is also involved in these processes. METHODS: ADAM10 expression was decreased by RNA interference and the effects of this on cell numbers, invasion and migration were determined. We also examined the effect of ADAM10 inhibition on breast cancer cell line invasion and migration. RESULTS: Using the triple-negative (TN) breast cancer cell lines, BT20, MDA-MB-231 and the non-TN cell line MDA-MB-453, knockdown of ADAM10 expression significantly decreased in vitro migration (P<0.01; for each cell line). Similarly, treatment with the ADAM10-selective inhibitor GI254023X reduced migration in the three cell lines (for BT20, P<0.001; for MDA-MB-231, P=0.005; for MDA-MB-453, P=0.023). In contrast, neither knockdown of ADAM10 nor treatment with the ADAM10-selective inhibitor GI254023X significantly affected cell numbers. Using extracts of primary breast cancers, higher levels of ADAM10 were found more frequently in high-grade vs low-grade tumours (P<0.001) and in oestrogen receptor (ER)-negative compared with ER-positive tumours (P=0.005). Analysis of pooled publicly available data sets found that high levels of ADAM10 mRNA were associated with adverse outcome in patients with the basal subtype of breast cancer. CONCLUSIONS: Based on our combined cell line and breast cancer extract data, we conclude that ADAM10 is likely to be involved in breast cancer progression, especially in the basal subtype. PMID- 26284335 TI - CTL- vs Treg lymphocyte-attracting chemokines, CCL4 and CCL20, are strong reciprocal predictive markers for survival of patients with oesophageal squamous cell carcinoma. AB - BACKGROUND: Tumoural infiltration of T lymphocytes is determined by local patterns of specific chemokine expression. In this report, we examined the roles of CCL4 and CCL20 in the accumulation of CD8(+) cytotoxic T lymphocytes (CTLs) and regulatory T (Treg) lymphocytes in oesophageal squamous cell carcinoma (ESCC), and determined the correlations between chemokine expressions and ESCC patients' survival. METHODS: Reverse transcriptase-PCR and immunohistochemistry (IHC) staining were performed to examine the expressions of interested genes. Flow cytometry was adopted to check the expressions of CCL4- and CCL6-specific receptors, CCR5 and CCR6, on CTLs and Treg cells. In addition, transwell assay was carried on. RESULTS: The CCL4 expression was significantly correlated with the expression of CTL markers (CD8 and Granzyme B), whereas CCL20 was positively correlated with Treg markers (FoxP3 and IL-10). Consistently, CCR5 was found to be mainly expressed on CD8(+) T lymphocytes, while CCR6 showed prevalence on Treg lymphocytes and the frequencies of CCR5(+)CD8(+) CTLs and CCR6(+) Treg cells were higher in TIL compared with PBMC. Respectively, CCL4 and CCL20 recruited CD8(+) and regulatory T cells in vitro. Importantly, high levels of CCL4 in the lesions of ESCC patients predicted prolonged survival. Furthermore, CCL4(high)/CCL20(low) group demonstrated better overall survival, whereas CCL4(low)/CCL20(low) and CCL4(low)/CCL20(high) groups showed the worst overall survival. CONCLUSIONS: Our data showed that CCL4 and CCL20 recruit functionally different T lymphocyte subsets into oesophageal carcinoma, indicating CCL4 and CCL20 are potential predictors of ESCC patients' survival. PMID- 26284336 TI - Comparison of the diagnostic workup of women referred at non-blinded or blinded double reading in a population-based screening mammography programme in the south of the Netherlands. AB - BACKGROUND: To determine whether referred women experience differences in diagnostic workup at non-blinded or blinded double reading of screening mammograms. METHODS: We included a consecutive series of respectively 42.996 and 44.491 screens, double read either in a non-blinded or blinded manner between 2009 and 2011. This reading strategy was alternated on a monthly basis. RESULTS: The overall ultrasound-guided core needle biopsy (CNB) rate and stereotactic CNB (SCNB) rate per 1000 screens were higher at blinded than at non-blinded reading (7.5 vs 6.0, P=0.008 and 8.1 vs 6.6, P=0.009). Among women with benign workup, these rates were higher at blinded reading (2.6 vs 1.4, P<0.001 and 5.9 vs 4.7, P=0.013). The benign biopsy rates were higher at blinded double reading (P<0.001), whereas the positive predictive value of biopsy did not differ (P=0.103). CONCLUSIONS: Blinded double-reading results in higher overall CNB and SCNB rates than non-blinded double reading, as well as a higher benign biopsy rate. PMID- 26284337 TI - Anti-apoptotic role and clinical relevance of neurotrophins in diffuse large B cell lymphomas. AB - BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a fatal malignancy that needs to identify new targets for additional therapeutic options. This study aimed to clarify the clinical and biological significance of endogenous neurotrophin (nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)) in DLBCL biopsy samples and cell lines. METHODS: We analysed expression of NGF, BDNF, and their receptors (Trk, p75(NTR)) in 51 biopsies and cell lines by immunohistochemistry, immunofluorescence, and western blotting. To investigate the biological role of BDNF/TrkB/p75(NTR) axis, effects of neurotrophin signalling inhibition were determined on tumour cell survival and vascular endothelial growth factor (VEGF) secretion. The pharmacological pan-Trk inhibitor K252a was used for in vitro and in vivo studies. RESULTS: A BDNF/TrkB axis was expressed in all biopsies, which was independent of the germinal centre B-cell (GCB)/non-GCB profile. p75(NTR), TrkB, and BDNF tumour scores were significantly correlated and high NGF expression was significantly associated with MUM1/IRF4, and the non-GCB subtype. Diffuse large B-cell lymphoma cell lines co-expressed neurotrophins and their receptors. The full-length TrkB receptor was found in all cell lines, which was also phosphorylated at Tyr-817. p75(NTR) was associated to Trk and not to its cell death co-receptor sortilin. In vitro, inhibition of neurotrophin signalling induced cell apoptosis. K252a caused cell apoptosis, decreased VEGF secretion, and potentiated rituximab effect, notably in less rituximab-sensitive cells. In vivo, K252a significantly reduced tumour growth and potentiated the effects of rituximab in a GCB-DLBCL xenograft model. CONCLUSIONS: This work argues for a pro-survival role of endogenous neurotrophins in DLBCLs and inhibition of Trk signalling might be a potential treatment strategy for rituximab resistant subgroups. PMID- 26284339 TI - Microgeographic Population Genetic Structure of Baylisascaris procyonis (Nematoda: Ascaroidae) in Western Michigan Indicates the Grand River Is a Barrier to Gene Flow. AB - Baylisascaris procyonis , the raccoon roundworm, is increasingly being recognized for its zoonotic and public health importance. Fine-scale analyses of the population genetics of this species have been hampered due to a lack of appropriate genetic markers. To this end, we developed 8 novel polymorphic microsatellites for B. procyonis and used these markers to elucidate microgeographic structuring of this parasite in a 500-km(2) study area in western Michigan. Our analyses revealed significant levels of genetic differentiation amongst the 74 worms collected from 10 different raccoons. Critically, Bayesian clustering indicated 2 genetically distinct groups, one on either side of the Grand River which bisects our study area. Estimates of F(ST), and results from AMOVA and isolation by distance, further corroborated a scenario whereby the river is acting as a barrier to gene flow, a rather unexpected finding given the high vagility of raccoons and microgeographic scale of the analysis. It is possible that the Grand River is a major dispersal barrier for B. procyonis because raccoons are most likely to disperse across the river when it is frozen, and worm burden in raccoons approaches zero during the winter. PMID- 26284338 TI - TLE3 is not a predictive biomarker for taxane sensitivity in the NCIC CTG MA.21 clinical trial. AB - BACKGROUND: TLE3, a nuclear transcriptional repressor downstream of WNT signalling pathways, has been hypothesised as predictive of benefit from adjuvant taxane. METHODS: MA.21 tissue microarrays were constructed from 1097 out of 2104 (52%) patients. TLE3 staining by immunohistochemistry used validated methodology. Continuous TLE3+ (percentage of cells staining positive) was assessed with both visual and automated scoring. The primary objective was to test the predictive effect of TLE3 on relapse-free survival using the MA.21 EC/T and CEF arms and the previously defined cut-point of 30% of cells staining positive in ?1 core/tumour. RESULTS: MA.21 patients had 83.2% TLE3 positive (TLE3+) tumours by visual score and 80.6% TLE3+ by automated image analysis while the previously observed rate of TLE3+ cases was 58.6%. TLE3 expression was significantly associated with ER expression (91.2% of ER-positive tumours were TLE3+; P<0.0001). At median 8-year follow-up, there was no evidence of a predictive effect of TLE3 expression with respect to taxane benefit using the established 30% or exploratory quartile cut points. CONCLUSIONS: Proportionately more MA.21 patient tumours than expected were TLE3+. The pre-specified TLE3+ cut-point of 30% was not predictive of taxane benefit. TLE3 expression does not represent a viable biomarker for taxane benefit in breast cancer. PMID- 26284340 TI - Theory and Practice of Lineage Tracing. AB - Lineage tracing is a method that delineates all progeny produced by a single cell or a group of cells. The possibility of performing lineage tracing initiated the field of Developmental Biology and continues to revolutionize Stem Cell Biology. Here, I introduce the principles behind a successful lineage-tracing experiment. In addition, I summarize and compare different methods for conducting lineage tracing and provide examples of how these strategies can be implemented to answer fundamental questions in development and regeneration. The advantages and limitations of each method are also discussed. PMID- 26284341 TI - Evolving 'self'-management: exploring the role of social network typologies on individual long-term condition management. AB - BACKGROUND: Whilst there has been a focus on the importance of social support for managing long-term conditions, there has been little specific focus on the characteristics of social networks that shape self-management. Policy emphasis is placed on individual responsibility for self-care, and this influences commissioning of health-care services. Assumptions are often made by policymakers about accessibility and preference for support and the influence of the social context on chronic illness management. OBJECTIVE: To examine the social networks of individuals with long-term conditions and identify how the characteristics of their composition influences support needs. DESIGN, SETTING AND PARTICIPANTS: Thirty participants completed initial face-to-face in-depth interviews, telephone follow-ups and final face-to-face interviews in the north-west of England. A longitudinal qualitative design was used to elicit the subtle changes in relationships over a year. FINDINGS: The findings suggest that the relationships which constitute a social network influence perceived support needs and attitudes to self-management. The amalgamation of relationships was characterized into three network typologies (family focused, friend focused or health-care professional focused) according to which types of relationships were dominant. In the absence of support, accounts highlighted a small number of substitutes who could provide support at times of critical need. DISCUSSION: This study challenges the notion of 'self'-management as an individual construct as many of the practices of illness management involved the support and/or negotiation of roles with others. By examining the nuances of relationships, this study has highlighted the tacit boundaries of practical and emotional support provision. PMID- 26284342 TI - Demographics and ocular biometric characteristics of patients undergoing cataract surgery in Auckland, New Zealand. AB - BACKGROUND: The aim is to investigate ethnic variation, in presentation and biometric parameters, within the population undergoing cataract surgery in Auckland. DESIGN: The design is a retrospective study. PARTICIPANTS: Four thousand nine hundred thirty-one eyes of 3524 consecutive patients undergoing cataract surgery in Auckland Public Hospital over 18 months were included in the study. METHODS: Analysis of preoperative medical records was performed. MAIN OUTCOME MEASURES: Age, gender, self-reported ethnicity, keratometry, anterior chamber depth, axial length and intraocular lens (IOL) power data were collected. RESULTS: Maori (4.7%) were under-represented compared with the proportion of Maori attending the eye clinic (5.5%) and in the major patient catchment area (8.2%). People of Maori, Pacific and Indian ethnicities presented at a significantly younger age (66.4, 65.9 and 67.9 years, respectively) than those of Caucasian and Asian ethnicities (76.4 and 71.3 years, respectively, P < 0.001). Advanced cataract was more likely in Pacific peoples and Maori than Caucasians. The mean axial length was longest in Asian eyes (23.83 +/- 1.52 mm). The mean anterior chamber depth in the eyes of Pacific peoples (3.20 +/- 0.39 mm) was significantly greater than that of Caucasians (3.09 +/- 0.42 mm, P = 0.001) and Asians (3.05 +/- 0.49 mm, P < 0.001). The mean IOL power in Asian eyes was 19.45D. This was significantly lower than the IOL power required by Caucasian (20.72D, P < 0.001) and Pacific ethnicities (20.61D, P = 0.001). With-the-rule astigmatism was highly prevalent in Maori and Pacific peoples, whereas in all other ethnicities, against-the-rule astigmatism was more common. CONCLUSIONS: This study identified significant ethnic variation in presentation for cataract surgery and ocular biometric parameters. These data may help identify potential biometric refinements and those at risk of developing ocular morbidities known to be associated with these parameters. PMID- 26284344 TI - Organophosphorus flame retardants and plasticizers in the aquatic environment: A case study of the Elbe River, Germany. AB - This study reports the occurrence and distribution of organophosphorus flame retardants and plasticizers (OPEs) in the Elbe and Rhine rivers. A special focus of this investigation concerns the potential impacts of a major flood event in 2013 on the OPE patterns and levels in the Elbe River. In this river, 6 of 13 OPEs were detected, with tris-ethyl-phosphate (TEP, 168 +/- 44 ng/L), tris-1,3 dichloro-2-propyl-phosphate (TDCPP, 155 +/- 14 ng/L) and tris-1-chloro-2-propyl phosphate (TCPP, 126 +/- 14 ng/L) identified as the dominant compounds. Relative to previous studies, an increase in the concentrations and relative contributions of TDCPP to the total level of OPEs was observed, which was likely caused by its increased use as a replacement for the technical pentaBDE formulation. During the flood event, the concentrations of OPEs were similar to the normal situation, but the mass fluxes increased by a factor of approximately ten (~16 kg/d normal versus ~160 kg/d flood peak). No input hotspots were identified along the transects of the Elbe and Rhine rivers, and the mass flux of OPEs appeared to be driven by water discharge. PMID- 26284345 TI - Exposure to environmentally-relevant levels of ozone negatively influence pollen and fruit development. AB - A combination of in vitro and in vivo studies on tomato (Lycopersicon esculentum Mill. cv. Triton) revealed that environmentally-relevant levels of ozone (O3) pollution adversely affected pollen germination, germ tube growth and pollen stigma interactions - pollen originating from plants raised in charcoal Purafil((r)) filtered air (CFA) exhibited reduced germ tube development on the stigma of plants exposed to environmentally-relevant levels of O3. The O3-induced decline in in vivo pollen viability was reflected in increased numbers of non fertilized and fertilized non-viable ovules in immature fruit. Negative effects of O3 on fertilization occurred regardless of the timing of exposure, with reductions in ovule viability evident in O3 * CFA and CFA * O3 crossed plants. This suggests O3-induced reductions in fertilization were associated with reduced pollen viability and/or ovule development. Fruit born on trusses independently exposed to 100 nmol mol(-1) O3 (10 h d(-1)) from flowering exhibited a decline in seed number and this was reflected in a marked decline in the weight and size of individual fruit - a clear demonstration of the direct consequence of the effects of the pollutant on reproductive processes. Ozone exposure also resulted in shifts in the starch and ascorbic acid (Vitamin C) content of fruit that were consistent with accelerated ripening. The findings of this study draw attention to the need for greater consideration of, and possibly the adoption of weightings for the direct impacts of O3, and potentially other gaseous pollutants, on reproductive biology during 'risk assessment' exercises. PMID- 26284346 TI - Eco-toxicity and human estrogenic exposure risks from OH-initiated photochemical transformation of four phthalates in water: A computational study. AB - Transformation products (TPs) of emerging organic contaminates (EOCs) in water are still rarely considered in environmental risk assessment, although some have been found to be concern. OH is believed as an important reactive species both in indirect phototransformation and advanced oxidation technology. Thus, eco toxicity and human estrogenic exposure risks of four phthalates and TPs during the OH-initiated photochemical process were investigated using computational approach. Four phthalates can be degraded through OH-addition and H-transfer pathways. The OH-addition TPs were predominant for dimethyl phthalates, while H transfer TPs were predominant for other three phthalates. Compared with phthalates, OH-addition TPs (o-OH-phthalates) were one level more toxic to aquatic organisms, and m-OH-phthalates exhibit higher estrogenic activity. Although H-transfer TPs were less harmful than OH-addition TPs, some of them still have aquatic toxicity and estrogenic activity. Therefore, more attentions should be paid to photochemical TPs and original EOCs, particularly those exhibiting high estrogenic activity to humans. PMID- 26284347 TI - Characterizations of wet mercury deposition on a remote high-elevation site in the southeastern Tibetan Plateau. AB - Accurate measurements of wet mercury (Hg) deposition are critically important for the assessment of ecological responses to pollutant loading. The Hg in wet deposition was measured over a 3-year period in the southeastern Tibetan Plateau. The volume-weighted mean (VWM) total Hg (HgT) concentration was somewhat lower than those reported in other regions of the Tibetan Plateau, but the VWM methyl Hg concentration and deposition flux were among the highest globally reported values. The VWM HgT concentration was higher in non-monsoon season than in monsoon season, and wet HgT deposition was dominated by the precipitation amount rather than the scavenging of atmospheric Hg by precipitation. The dominant Hg species in precipitation was mainly in the form of dissolved Hg, which indicates the pivotal role of reactive gaseous Hg within-cloud scavenging to wet Hg deposition. Moreover, an increasing trend in precipitation Hg concentrations was synchronous with the recent economic development in South Asia. PMID- 26284348 TI - Polycyclic aromatic hydrocarbons in caribou, moose, and wolf scat samples from three areas of the Alberta oil sands. AB - Impacts of toxic substances from oil production in the Alberta oil sands (AOS), such as polycyclic aromatic hydrocarbons (PAHs), have been widely debated. Studies have been largely restricted to exposures from surface mining in aquatic species. We measured PAHs in Woodland caribou (Rangifer tarandus caribou), moose (Alces americanus), and Grey wolf (Canis lupus) across three areas that varied in magnitude of in situ oil production. Our results suggest a distinction of PAH level and source profile (petro/pyrogenic) between study areas and species. Caribou samples indicated pyrogenic sourced PAHs in the study area previously devastated by forest fire. Moose and wolf samples from the high oil production area demonstrated PAH ratios indicative of a petrogenic source and increased PAHs, respectively. These findings emphasize the importance of broadening monitoring and research programs in the AOS. PMID- 26284349 TI - Long-term Patient Outcomes After Microsurgical Treatment of Blister-Like Aneurysms of the Basilar Artery. AB - BACKGROUND: Blister-like aneurysms (BLAs) are challenging lesions that require unique microsurgical strategies. BLAs are predominantly found along the internal carotid artery; however, BLAs of the basilar artery are a rare subset that requires a modified treatment strategy. OBJECTIVE: To discuss the microsurgical management and review the long-term outcomes of patients with BLAs of the basilar artery. METHODS: We retrospectively reviewed the surgical technique, postoperative results, and long-term outcomes of all patients with basilar artery BLAs treated at our institution from 2005 to 2011. RESULTS: Four patients with basilar artery BLAs were identified over this 6-year interval. All 4 patients were treated by direct microsurgical clipping. A thin layer of cotton reinforcement was used beneath the clip tines to minimize the risk of clip slippage in 2 of 4 patients; 1 patient required adjunctive endovascular stent placement for residual aneurysm after clipping. Complete obliteration of all aneurysms was achieved, and there has been no recurrence at mean clinical follow up of 72 months (median, 74.5; range, 37-103) and imaging follow-up of 48 months (median, 54; range 12-72). CONCLUSION: Direct clipping with or without cotton reinforcement can obliterate basilar BLAs with excellent long-term outcomes. Clip wrapping is not an option for these lesions given the proximity to perforating branches. Endovascular techniques provide a useful adjunctive strategy; however, risks with antiplatelet therapy in the acute subarachnoid hemorrhage period must be considered. PMID- 26284350 TI - Use of Actuator-Driven Pulsed Water Jet in Brain and Spinal Cord Cavernous Malformations Resection. AB - BACKGROUND: A piezo actuator-driven pulsed water jet (ADPJ) system is a novel surgical instrument that enables dissection of tissue without thermal damage. It can potentially resect intra-axial lesions while preserving neurological function. OBJECTIVE: To report our first experience of applying an ADPJ system to brain and spinal cord cavernous malformations. METHODS: Four patients (2 women and 2 men, mean age 44.5 years) with brain (n = 3) and spinal cord (n = 1) cavernous malformations were enrolled in the study. All surgeries were performed with the aid of the ADPJ system. Postoperative neurological function and radiological findings were evaluated. RESULTS: The ADPJ system was useful in dissecting boundaries between the lesion and surrounding brain/spinal cord tissues. The pulsed water jet provided a clear surgical view and helped surgeons follow the margins. Water jet dissection peeled off the brain and spinal cord tissues from the lesion wall. Surrounding gliotic tissue was preserved. As a consequence, the cavernous malformations were successfully removed. Postoperative magnetic resonance imaging confirmed total removal of lesions in all cases. Preoperative neurological symptoms completely resolved in 2 patients. The others experienced partial recovery. No patients developed new postoperative neurological deficits; facial palsy temporarily worsened in 1 patient who underwent a suprafacial colliculus approach for the brainstem lesion. CONCLUSION: The ADPJ provided a clear surgical field and enabled surgeons to dissect boundaries between lesions and surrounding brain and spinal cord gliotic tissue. The ADPJ system is a feasible option for cavernous malformation surgery, enabling successful tumor removal and preservation of neurological function. PMID- 26284352 TI - Endoscopic Transsphenoidal Pituitary Surgery: Recurrent Pituitary Adenoma: 3 Dimensional Operative Video. PMID- 26284351 TI - Feasibility, Safety, and Periprocedural Complications of Pipeline Embolization for Intracranial Aneurysm Treatment Under Conscious Sedation: University at Buffalo Neurosurgery Experience. AB - BACKGROUND: Endovascular Pipeline Embolization Device (PED) placement for intracranial aneurysms is performed under general anesthesia at most centers because of perceived improved image quality and patient safety. OBJECTIVE: To report the feasibility, safety, and outcomes associated with the use of the PED for intracranial aneurysms performed in awake patients after the administration of conscious sedation (CS) and a local anesthetic. METHODS: Between March 2012 and September 2014, 130 patients with 139 intracranial aneurysms (8 ruptured) were treated with the PED under CS at our institution. Procedure details and time (including duration, radiation exposure, and fluoroscopy) and procedure-related complications were retrospectively reviewed. RESULTS: A total of 155 PED deployment procedures were performed under CS. Treatment was successfully completed in all cases. Anesthesia was converted from CS to general anesthesia during 5 procedures. Mean interval from patient entry at the endovascular suite to procedure initiation was 18 minutes (range, 5 minutes-1 hour 10 minutes). Mean procedure length was 1 hour 25 minutes (range, 30 minutes-3 hours 51 minutes). Mean +/- SD values for fluoroscopy time and radiation exposure were 36.17 +/- 18.4 minutes and 1367 +/- 897 mGy, respectively. The mean amount of contrast material administered was 211.37 +/- 83.5 mL. Permanent neurological complications were seen in 4 patients (3%). CONCLUSION: In our experience, CS for PED placement for intracranial aneurysm treatment is feasible and safe. Procedure and fluoroscopy times and amount of radiation exposure are similar to or less than described in reports of PED placement under general anesthesia. CS allows direct neurological evaluation and earlier detection of and response to intraprocedural complications. PMID- 26284353 TI - Direct Repair of Iatrogenic Internal Carotid Artery Injury During Endoscopic Endonasal Approach Surgery With Temporary Endovascular Balloon-Assisted Occlusion: Technical Case Report. AB - BACKGROUND AND IMPORTANCE: Iatrogenic internal carotid artery (ICA) injuries during endoscopic endonasal approach (EEA) surgeries are associated with a high morbidity and mortality, with few acceptable methods described for repair. CLINICAL PRESENTATION: A 13-year-old girl with a large anterior and central skull base osteoblastoma incurred an iatrogenic cavernous ICA injury during a staged EEA approach. Intraoperative angiogram was performed with balloon-assisted EEA primary microsurgical repair of the lacerated ICA. CONCLUSION: By integrating current techniques commonly used in open aneurysm surgeries and in endovascular procedures, we developed a rapid, safe technique to repair an EEA-associated iatrogenic ICA injury. PMID- 26284354 TI - Quantifying Pharmaceutical Film Coating with Optical Coherence Tomography and Terahertz Pulsed Imaging: An Evaluation. AB - Spectral domain optical coherence tomography (OCT) has recently attracted a lot of interest in the pharmaceutical industry as a fast and non-destructive modality for quantification of thin film coatings that cannot easily be resolved with other techniques. Because of the relative infancy of this technique, much of the research to date has focused on developing the in-line measurement technique for assessing film coating thickness. To better assess OCT for pharmaceutical coating quantification, this paper evaluates tablets with a range of film coating thickness measured using OCT and terahertz pulsed imaging (TPI) in an off-line setting. In order to facilitate automated coating quantification for film coating thickness in the range of 30-200 MUm, an algorithm that uses wavelet denoising and a tailored peak finding method is proposed to analyse each of the acquired A scan. Results obtained from running the algorithm reveal an increasing disparity between the TPI and OCT measured intra-tablet variability when film coating thickness exceeds 100 MUm. The finding further confirms that OCT is a suitable modality for characterising pharmaceutical dosage forms with thin film coatings, whereas TPI is well suited for thick coatings. PMID- 26284355 TI - Rapid Reduction of the Diferric-Peroxyhemiacetal Intermediate in Aldehyde Deformylating Oxygenase by a Cyanobacterial Ferredoxin: Evidence for a Free Radical Mechanism. AB - Aldehyde-deformylating oxygenase (ADO) is a ferritin-like nonheme-diiron enzyme that catalyzes the last step in a pathway through which fatty acids are converted into hydrocarbons in cyanobacteria. ADO catalyzes conversion of a fatty aldehyde to the corresponding alk(a/e)ne and formate, consuming four electrons and one molecule of O2 per turnover and incorporating one atom from O2 into the formate coproduct. The source of the reducing equivalents in vivo has not been definitively established, but a cyanobacterial [2Fe-2S] ferredoxin (PetF), reduced by ferredoxin-NADP(+) reductase (FNR) using NADPH, has been implicated. We show that both the diferric form of Nostoc punctiforme ADO and its (putative) diferric-peroxyhemiacetal intermediate are reduced much more rapidly by Synechocystis sp. PCC6803 PetF than by the previously employed chemical reductant, 1-methoxy-5-methylphenazinium methyl sulfate. The yield of formate and alkane per reduced PetF approaches its theoretical upper limit when reduction of the intermediate is carried out in the presence of FNR. Reduction of the intermediate by either system leads to accumulation of a substrate-derived peroxyl radical as a result of off-pathway trapping of the C2-alkyl radical intermediate by excess O2, which consequently diminishes the yield of the hydrocarbon product. A sulfinyl radical located on residue Cys71 also accumulates with short-chain aldehydes. The detection of these radicals under turnover conditions provides the most direct evidence to date for a free-radical mechanism. Additionally, our results expose an inefficiency of the enzyme in processing its radical intermediate, presenting a target for optimization of bioprocesses exploiting this hydrocarbon-production pathway. PMID- 26284356 TI - Treatment of localized mycosis fungoides with digital UV photochemotherapy. AB - BACKGROUND/PURPOSE: Photochemochemotherapy with 8-methoxypsoralen and UV-A light (PUVA) is a well-established treatment for mycosis fungoides (MF), although evidence for this therapy by means of prospective studies is scarce. However, long-term risks of PUVA are premature skin aging and development of nonmelanoma skin cancer. We therefore evaluated a device for targeted UV therapy, which reduces irradiation of unaffected skin in MF patients. METHODS: Ten patients with patch- or plaque-type MF affecting less than 10% body surface area were included in a prospective study. A total of 14 lesions were treated with cream PUVA using the digital phototherapy device skintrek((r)) PT3. RESULTS: Seven of ten patients showed response to treatment. Complete clinical remission was achieved in four of ten patients (complete remission of seven of fourteen treated lesions) after an average of 13.4 weeks and an average cumulative UV dose of 42.6 J/cm(2) in a mean of 31.2 treatment sessions. Adverse events were rare and of mild severity. CONCLUSIONS: This study is the first prospective trial demonstrating efficacy and safety of cream PUVA in MF patients. As healthy adjacent skin remains unaffected, the potential to reduce the carcinogenic risk of PUVA treatment makes this new method a promising therapeutic option for localized MF. PMID- 26284357 TI - An Economic Assessment Model of Rural and Remote Satellite Hemodialysis Units. AB - BACKGROUND: Kidney Failure is epidemic in many remote communities in Canada. In centre hemodialysis is provided within these settings in satellite hemodialysis units. The key cost drivers of this program have not been fully described. Such information is important in informing the design of programs aimed at optimizing efficiency in providing dialysis and preventative chronic kidney disease care in remote communities. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We constructed a cost model based on data derived from 16 of Manitoba, Canada's remote satellite units. We included all costs for operation of the unit, transportation, treatment, and capital costs. All costs were presented in 2013 Canadian dollars. RESULTS: The annual per-patient cost of providing hemodialysis in the satellite units ranged from $80,372 to $215,918 per patient, per year. The median per patient, per year cost was $99,888 (IQR $89,057-$122,640). Primary cost drivers were capital costs related to construction, human resource expenses, and expenses for return to tertiary care centres for health care. Costs related to transport considerably increased estimates in units that required plane or helicopter transfers. CONCLUSIONS: Satellite hemodialysis units in remote areas are more expensive on a per-patient basis than hospital hemodialysis and satellite hemodialysis available in urban areas. In some rural, remote locations, better value for money may reside in local surveillance and prevention programs in addition support for home dialysis therapies over construction of new satellite hemodialysis units. PMID- 26284358 TI - Correction: Bank Vole Prion Protein As an Apparently Universal Substrate for RT QuIC-Based Detection and Discrimination of Prion Strains. PMID- 26284360 TI - Utilization of Copper-Catalyzed Carboarylation-Ring Closure for the Synthesis of New Oxazoline Derivatives. AB - A copper-catalyzed carboarylation-ring-closure strategy was used for the modular synthesis of oxazolines via the reaction of 1-aryl- and 1-alkylpropargylamides and diaryliodonium salts. The novel approach enables the efficient, modular synthesis of oxazoline derivatives bearing fully substituted exo double bonds. PMID- 26284359 TI - The Association of Outdoor Activity and Age-Related Cataract in a Rural Population of Taizhou Eye Study: Phase 1 Report. AB - PURPOSE: To study the relationship between outdoor activity and risk of age related cataract (ARC) in a rural population of Taizhou Eye Study (phrase 1 report). METHOD: A population-based, cross-sectional study of 2006 eligible rural adults (>=45 years old) from Taizhou Eye Study was conducted from Jul. to Sep. 2012. Participants underwent detailed ophthalmologic examinations including uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), intraocular pressure (IOP), slit lamp and fundus examinations as well as questionnaires about previous outdoor activity and sunlight protection methods. ARC was recorded by LOCSIII classification system. The prevalence of cortical, nuclear and posterior subcapsular cataract were assessed separately for the risk factors and its association with outdoor activity. RESULTS: Of all 2006 eligible participants, 883 (44.0%) adults were diagnosed with ARC. The prevalence rates of cortical, nuclear and posterior subcapsular cataract per person were 41.4%, 30.4% and 1.5%, respectively. Women had a higher tendency of nuclear and cortical cataract than men (OR = 1.559, 95% CI 1.204-2.019 and OR = 1.862, 95% CI 1.456 2.380, respectively). Adults with high myopia had a higher prevalence of nuclear cataract than adults without that (OR = 2.528, 95% CI 1.055-6.062). Multivariable logistic regression revealed that age was risk factor of nuclear (OR = 1.190, 95% CI 1.167-1.213) and cortical (OR = 1.203, 95% CI 1.181-1.226) cataract; eyes with fundus diseases was risk factor of posterior subcapsular cataract (OR = 6.529, 95% CI 2.512-16.970). Outdoor activity was an independent risk factor of cortical cataract (OR = 1.043, 95% CI 1.004-1.083). The risk of cortical cataract increased 4.3% (95% CI 0.4%-8.3%) when outdoor activity time increased every one hour. Furthermore, the risk of cortical cataract increased 1.1% (95% CI 0.1% 2.0%) when cumulative UV-B exposure time increased every one year. CONCLUSION: Outdoor activity was an independent risk factor for cortical cataract, but was not risk factor for nuclear and posterior subcapsular cataract. The risk of cortical cataract increased 4.3% when outdoor activity time increased every one hour. In addition, the risk of cortical cataract increased 1.1% (95% CI 0.1% 2.0%) when cumulative UV-B exposure time increased every one year. PMID- 26284361 TI - Human Dynactin-Associated Protein Transforms NIH3T3 Cells to Generate Highly Vascularized Tumors with Weak Cell-Cell Interaction. AB - Human dynactin-associated protein (dynAP) is a transmembrane protein that promotes AktSer473 phosphorylation. Here, we report the oncogenic properties of dynAP. In contrast to control NIH3T3 cells expressing LacZ (NIH3T3LacZ), NIH3T3dynAP cells vigorously formed foci in two-dimensional culture, colonies on soft agar, and spheroids in anchorage-deficient three-dimensional culture. NIH3T3dynAP cells injected into nude mice produced tumors with abundant blood vessels and weak cell-cell contacts. Expression of dynAP elevated the level of rictor (an essential subunit of mTORC2) and promoted phosphorylation of FOXO3aSer253. FOXO3a is a transcriptional factor that stimulates expression of pro-apoptotic genes and phosphorylation of FOXO3a abrogates its function, resulting in promoted cell survival. Knockdown of rictor in NIH3T3dynAP cells reduced AktSer473 phosphorylation and formation of foci, colony in soft agar and spheroid, indicating that dynAP-induced activation of the mTORC2/AktSer473 pathway for cell survival contributes to cell transformation. E-cadherin and its mRNA were markedly reduced upon expression of dynAP, giving rise to cells with higher motility, which may be responsible for the weak cell-cell adhesion in tumors. Thus, dynAP could be a new oncoprotein and a target for cancer therapy. PMID- 26284362 TI - Distribution of Peripheral Memory T Follicular Helper Cells in Patients with Schistosomiasis Japonica. AB - BACKGROUND: Schistosomiasis is a helminthic disease that affects more than 200 million people. An effective vaccine would be a major step towards eliminating the disease. Studies suggest that T follicular helper (Tfh) cells provide help to B cells to generate the long-term humoral immunity, which would be a crucial component of successful vaccines. Thus, understanding the biological characteristics of Tfh cells in patients with schistosomiasis, which has never been explored, is essential for vaccine design. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the biological characteristics of peripheral memory Tfh cells in schistosomiasis patients by flow cytometry. Our data showed that the frequencies of total and activated peripheral memory Tfh cells in patients were significantly increased during Schistosoma japonicum infection. Moreover, Tfh2 cells, which were reported to be a specific subpopulation to facilitate the generation of protective antibodies, were increased more greatly than other subpopulations of total peripheral memory Tfh cells in patients with schistosomiasis japonica. More importantly, our result showed significant correlations of the percentage of Tfh2 cells with both the frequency of plasma cells and the level of IgG antibody. In addition, our results showed that the percentage of T follicular regulatory (Tfr) cells was also increased in patients with schistosomiasis. CONCLUSIONS/SIGNIFICANCE: Our report is the first characterization of peripheral memory Tfh cells in schistosomasis patients, which not only provides potential targets to improve immune response to vaccination, but also is important for the development of vaccination strategies to control schistosomiasis. PMID- 26284364 TI - Impaired Maternal Behavior in Usp46 Mutant Mice: A Model for Trans-Generational Transmission of Maternal Care. AB - Usp46 mutant mice (congenic strain on a B6 genetic background; MT mice) have a low weaning rate and display poor maternal behavior compared to C57BL/6J mice (B6 mice). Based on these observations, we examined how maternal behavior is shaped by cross-fostering and in-fostering MT and B6 mice. The experiments consisted of six groups: B6 mice fostered by their biological mother (B6-CO); MT mice fostered by their biological mother (MT-CO); B6 mice fostered by a different B6 mother (B6 IF); MT mice fostered by a different MT mother (MT-IF); B6 mice fostered by an MT mother (B6-CF); and MT mice fostered by a B6 mother (MT-CF). Maternal behavior was assessed using the pup-retrieval test in adult female offspring, and four parameters, time nursing pups in the nest, time sniffing or licking pups, rearing behavior, and latency to retrieve pups, were measured. Cross-fostering significantly reduced time spent nursing and sniffing/licking pup, and increased the number of instances of rearing in the B6-CF group, and improved three parameters of maternal behaviors (nursing, rearing and latency) in the MT-CF group. These results indicate that the level of maternal care is transmitted to their pups and proper maternal behaviors can be shaped if adequate postpartum maternal care is given, even in genetically vulnerable mice. However, the offspring's genotype may also influence the development of maternal behaviors in adulthood. Thus, MT mice may prove useful as a model for trans-generational transmission of maternal care, and these findings may provide insight into the mechanisms of maltreating behaviors in human child abuse. PMID- 26284363 TI - Amniotic Membrane Modifies the Genetic Program Induced by TGFbeta, Stimulating Keratinocyte Proliferation and Migration in Chronic Wounds. AB - BACKGROUND: Post-traumatic large-surface or deep wounds often cannot progress to reepithelialisation because they become irresponsive in the inflammatory stage, so intervention is necessary to provide the final sealing epidermis. Previously we have shown that Amniotic Membrane (AM) induced a robust epithelialisation in deep traumatic wounds. METHODS AND FINDINGS: To better understand this phenomenon, we used keratinocytes to investigate the effect of AM on chronic wounds. Using keratinocytes, we saw that AM treatment is able to exert an attenuating effect upon Smad2 and Smad3 TGFbeta-induced phosphorylation while triggering the activation of several MAPK signalling pathways, including ERK and JNK1, 2. This also has a consequence for TGFbeta-induced regulation on cell cycle control key players CDK1A (p21) and CDK2B (p15). The study of a wider set of TGFbeta regulated genes showed that the effect of AM was not wide but very concrete for some genes. TGFbeta exerted a powerful cell cycle arrest; the presence of AM however prevented TGFbeta-induced cell cycle arrest. Moreover, AM induced a powerful cell migration response that correlates well with the expression of c-Jun protein at the border of the healing assay. Consistently, the treatment with AM of human chronic wounds induced a robust expression of c-Jun at the wound border. CONCLUSIONS: The effect of AM on the modulation of TGFbeta responses in keratinocytes that favours proliferation together with AM-induced keratinocyte migration is the perfect match that allows chronic wounds to move on from their non-healing state and progress into epithelialization. Our results may explain why the application of AM on chronic wounds is able to promote epithelialisation. PMID- 26284365 TI - Lifetime Dependent Variation of Stress Hormone Metabolites in Feces of Two Laboratory Mouse Strains. AB - Non-invasive measurement of stress hormone metabolites in feces has become routine practice for the evaluation of distress and pain in animal experiments. Since metabolism and excretion of glucocorticoids may be variable, awareness and adequate consideration of influencing factors are essential for accurate monitoring of adrenocortical activity. Reference values are usually provided by baselines compiled prior to the experiment and by age matched controls. The comparison of stress hormone levels between animals of different ages or between studies looking at hormone levels at the beginning and at the end of a long term study might be biased by age-related effects. In this study we analyzed fecal corticosterone metabolites (FCM) during the lifetime of untreated female mice of the strains C57BL/6NCrl and Crl:CD1. For this purpose feces for each individual mouse were collected every two months over a period of 24 hours, at intervals of four hours, until the age of 26 months. Results of the study revealed that age of the animals had a significant impact on the level and circadian rhythm of stress hormone metabolites. Furthermore, long-term observation of mice revealed a strain specific excretion profile of FCM influenced by strong seasonal variability. PMID- 26284366 TI - Motivational Modulation of Self-Initiated and Externally Triggered Movement Speed Induced by Threat of Shock: Experimental Evidence for Paradoxical Kinesis in Parkinson's Disease. AB - BACKGROUND: Paradoxical kinesis has been observed in bradykinetic people with Parkinson's disease. Paradoxical kinesis occurs in situations where an individual is strongly motivated or influenced by relevant external cues. Our aim was to induce paradoxical kinesis in the laboratory. We tested whether the motivation of avoiding a mild electric shock was sufficient to induce paradoxical kinesis in externally-triggered and self-initiated conditions in people with Parkinson's disease tested on medication and in age-matched controls. METHODS: Participants completed a shock avoidance behavioural paradigm in which half of the trials could result in a mild electric shock if the participant did not move fast enough. Half of the trials of each type were self-initiated and half were externally-triggered. The criterion for avoiding shock was a maximum movement time, adjusted according to each participant's performance on previous trials using a staircase tracking procedure. RESULTS: On trials with threat of shock, both patients with Parkinson's disease and controls had faster movement times compared to no potential shock trials, in both self-initiated and externally triggered conditions. The magnitude of improvement of movement time from no potential shock to potential shock trials was positively correlated with anxiety ratings. CONCLUSIONS: When motivated to avoid mild electric shock, patients with Parkinson's disease, similar to healthy controls, showed significant speeding of movement execution. This was observed in both self-initiated and externally triggered versions of the task. Nevertheless, in the ET condition the improvement of reaction times induced by motivation to avoid shocks was greater for the PD patients than controls, highlighting the value of external cues for movement initiation in PD patients. The magnitude of improvement from the no potential shock to the potential shock trials was associated with the threat-induced anxiety. This demonstration of paradoxical kinesis in the laboratory under both self-initiated and externally-triggered conditions has implications for motivational and attentional enhancement of movement speed in Parkinson's disease. PMID- 26284369 TI - Correction: A Transposable Element within the Non-canonical Telomerase RNA of Arabidopsis thaliana Modulates Telomerase in Response to DNA Damage. PMID- 26284368 TI - The Association between Parameters of Malnutrition and Diagnostic Measures of Sarcopenia in Geriatric Outpatients. AB - OBJECTIVES: Diagnostic criteria for sarcopenia include measures of muscle mass, muscle strength and physical performance. Consensus on the definition of sarcopenia has not been reached yet. To improve insight into the most clinically valid definition of sarcopenia, this study aimed to compare the association between parameters of malnutrition, as a risk factor in sarcopenia, and diagnostic measures of sarcopenia in geriatric outpatients. MATERIAL AND METHODS: This study is based on data from a cross-sectional study conducted in a geriatric outpatient clinic including 185 geriatric outpatients (mean age 82 years). Parameters of malnutrition included risk of malnutrition (assessed by the Short Nutritional Assessment Questionnaire), loss of appetite, unintentional weight loss and underweight (body mass index <22 kg/m2). Diagnostic measures of sarcopenia included relative muscle mass (lean mass and appendicular lean mass [ALM] as percentages), absolute muscle mass (total lean mass and ALM/height2), handgrip strength and walking speed. All diagnostic measures of sarcopenia were standardized. Associations between parameters of malnutrition (independent variables) and diagnostic measures of sarcopenia (dependent variables) were analysed using multivariate linear regression models adjusted for age, body mass, fat mass and height in separate models. RESULTS: None of the parameters of malnutrition was consistently associated with diagnostic measures of sarcopenia. The strongest associations were found for both relative and absolute muscle mass; less stronger associations were found for muscle strength and physical performance. Underweight (p = <0.001) and unintentional weight loss (p = 0.031) were most strongly associated with higher lean mass percentage after adjusting for age. Loss of appetite (p = 0.003) and underweight (p = 0.021) were most strongly associated with lower total lean mass after adjusting for age and fat mass. CONCLUSION: Parameters of malnutrition relate differently to diagnostic measures of sarcopenia in geriatric outpatients. The association between parameters of malnutrition and diagnostic measures of sarcopenia was strongest for both relative and absolute muscle mass, while less strong associations were found with muscle strength and physical performance. PMID- 26284367 TI - The Impact of Water, Sanitation and Hygiene Interventions to Control Cholera: A Systematic Review. AB - BACKGROUND AND METHODS: Cholera remains a significant threat to global public health with an estimated 100,000 deaths per year. Water, sanitation and hygiene (WASH) interventions are frequently employed to control outbreaks though evidence regarding their effectiveness is often missing. This paper presents a systematic literature review investigating the function, use and impact of WASH interventions implemented to control cholera. RESULTS: The review yielded eighteen studies and of the five studies reporting on health impact, four reported outcomes associated with water treatment at the point of use, and one with the provision of improved water and sanitation infrastructure. Furthermore, whilst the reporting of function and use of interventions has become more common in recent publications, the quality of studies remains low. The majority of papers (>60%) described water quality interventions, with those at the water source focussing on ineffective chlorination of wells, and the remaining being applied at the point of use. Interventions such as filtration, solar disinfection and distribution of chlorine products were implemented but their limitations regarding the need for adherence and correct use were not fully considered. Hand washing and hygiene interventions address several transmission routes but only 22% of the studies attempted to evaluate them and mainly focussed on improving knowledge and uptake of messages but not necessarily translating this into safer practices. The use and maintenance of safe water storage containers was only evaluated once, under-estimating the considerable potential for contamination between collection and use. This problem was confirmed in another study evaluating methods of container disinfection. One study investigated uptake of household disinfection kits which were accepted by the target population. A single study in an endemic setting compared a combination of interventions to improve water and sanitation infrastructure, and the resulting reductions in cholera incidence. DISCUSSION AND RECOMMENDATIONS: This review highlights a focus on particular routes of transmission, and the limited number of interventions tested during outbreaks. There is a distinct gap in knowledge of which interventions are most appropriate for a given context and as such a clear need for more robust impact studies evaluating a wider array of WASH interventions, in order to ensure effective cholera control and the best use of limited resources. PMID- 26284370 TI - Distributed Bayesian Computation and Self-Organized Learning in Sheets of Spiking Neurons with Local Lateral Inhibition. AB - During the last decade, Bayesian probability theory has emerged as a framework in cognitive science and neuroscience for describing perception, reasoning and learning of mammals. However, our understanding of how probabilistic computations could be organized in the brain, and how the observed connectivity structure of cortical microcircuits supports these calculations, is rudimentary at best. In this study, we investigate statistical inference and self-organized learning in a spatially extended spiking network model, that accommodates both local competitive and large-scale associative aspects of neural information processing, under a unified Bayesian account. Specifically, we show how the spiking dynamics of a recurrent network with lateral excitation and local inhibition in response to distributed spiking input, can be understood as sampling from a variational posterior distribution of a well-defined implicit probabilistic model. This interpretation further permits a rigorous analytical treatment of experience dependent plasticity on the network level. Using machine learning theory, we derive update rules for neuron and synapse parameters which equate with Hebbian synaptic and homeostatic intrinsic plasticity rules in a neural implementation. In computer simulations, we demonstrate that the interplay of these plasticity rules leads to the emergence of probabilistic local experts that form distributed assemblies of similarly tuned cells communicating through lateral excitatory connections. The resulting sparse distributed spike code of a well-adapted network carries compressed information on salient input features combined with prior experience on correlations among them. Our theory predicts that the emergence of such efficient representations benefits from network architectures in which the range of local inhibition matches the spatial extent of pyramidal cells that share common afferent input. PMID- 26284372 TI - Assessing the Effectiveness of Local Management of Coral Reefs Using Expert Opinion and Spatial Bayesian Modeling. AB - Multiple stressors are an increasing concern in the management and conservation of ecosystems, and have been identified as a key gap in research. Coral reefs are one example of an ecosystem where management of local stressors may be a way of mitigating or delaying the effects of climate change. Predicting how multiple stressors interact, particularly in a spatially explicit fashion, is a difficult challenge. Here we use a combination of an expert-elicited Bayesian network (BN) and spatial environmental data to examine how hypothetical scenarios of climate change and local management would result in different outcomes for coral reefs on the Great Barrier Reef (GBR), Australia. Parameterizing our BN using the mean responses from our experts resulted in predictions of limited efficacy of local management in combating the effects of climate change. However, there was considerable variability in expert responses and uncertainty was high. Many reefs within the central GBR appear to be at risk of further decline based on the pessimistic opinions of our expert pool. Further parameterization of the model as more data and knowledge become available could improve predictive power. Our approach serves as a starting point for subsequent work that can fine-tune parameters and explore uncertainties in predictions of responses to management. PMID- 26284373 TI - Risk Factors for the Failure of Spinal Burst Fractures Treated Conservatively According to the Thoracolumbar Injury Classification and Severity Score (TLICS): A Retrospective Cohort Trial. AB - BACKGROUND: The management of thoracolumbar (TL) burst fractures is still controversial. The thoracolumbar injury classification and severity score (TLICS) algorithm is now widely used to guide clinical decision making, however, in clinical practice, we come to realize that TLICS also has its limitations for treating patients with total scores less than 4, for which conservative treatment may not be optimal in all cases. PURPOSE: The aim of this study is to identify several risk factors for the failure of conservative treatment of TL burst fractures according to TLICS algorithm. METHODS: From June 2008 to December 2013, a cohort of 129 patients with T10-l2 TL burst fractures with a TLISC score <=3 treated non-operatively were identified and included into this retrospective study. Age, sex, pain intensity, interpedicular distance (IPD), canal compromise, loss of vertebral body height and kyphotic angle (KA) were selected as potential risk factors and compared between the non-operative success group and the non operative failure group. RESULTS: One hundred and four patients successfully completed non-operative treatment, the other 25 patients were converted to surgical treatment because of persistent local back pain or progressive neurological deficits during follow-up. Our results showed that age, visual analogue scale (VAS) score and IPD, KA were significantly different between the two groups. Furthermore, regression analysis indicated that VAS score and IPD could be considered as significant predictors for the failure of conservative treatment. CONCLUSION: The recommendation of non-operative treatment for TLICS score <=3 has limitations in some patients, and VAS score and IPD could be considered as risk factors for the failure of conservative treatment. Thus, conservative treatment should be decided with caution in patients with greater VAS scores or IPD. If non-operative management is decided, a close follow-up is necessary. PMID- 26284371 TI - In Vitro Protective Effect and Antioxidant Mechanism of Resveratrol Induced by Dapsone Hydroxylamine in Human Cells. AB - Dapsone (DDS) hydroxylamine metabolites cause oxidative stress- linked adverse effects in patients, such as methemoglobin formation and DNA damage. This study evaluated the ameliorating effect of the antioxidant resveratrol (RSV) on DDS hydroxylamine (DDS-NHOH) mediated toxicity in vitro using human erythrocytes and lymphocytes. The antioxidant mechanism was also studied using in-silico methods. In addition, RSV provided intracellular protection by inhibiting DNA damage in human lymphocytes induced by DDS-NHOH. However, whilst pretreatment with RSV (10 1000 MUM significantly attenuated DDS-NHOH-induced methemoglobinemia, but it was not only significantly less effective than methylene blue (MET), but also post treatment with RSV did not reverse methemoglobin formation, contrarily to that observed with MET. DDS-NHOH inhibited catalase (CAT) activity and reactive oxygen species (ROS) generation, but did not alter superoxide dismutase (SOD) activity in erythrocytes. Pretreatment with RSV did not alter these antioxidant enzymes activities in erythrocytes treated with DDS-NHOH. Theoretical calculations using density functional theory methods showed that DDS-NHOH has a pro-oxidant effect, whereas RSV and MET have antioxidant effect on ROS. The effect on methemoglobinemia reversion for MET was significantly higher than that of RSV. These data suggest that the pretreatment with resveratrol may decrease heme-iron oxidation and DNA damage through reduction of ROS generated in cells during DDS therapy. PMID- 26284374 TI - Characteristics of Improvised Explosive Device Trauma Casualties in the Gaza Strip and Other Combat Regions: The Israeli Experience. AB - OBJECTIVE: Low-intensity conflict is characterized in asymmetrical conventional and nonconventional warfare. The use of improvised explosive devices (IEDs) in the Israeli-Palestinian conflict has evolved over the past few decades to include the addition of diesel, biological agents, shrapnel, and nitroglycerin to the explosive content. Due to its nature and mechanism, an IED injury might present as a multidimensional injury, impairing numerous systems and organs. MATERIALS AND METHODS: The authors present a case series of 5 Israeli Defense Forces (IDF) soldiers wounded by an IED presenting a typical and similar pattern of burns to their faces, trunks, and limbs, in addition to ocular, ear/nose/throat, and orthopedic injuries. An analysis of the experience in treating the aforementioned injuries is included. RESULTS: Improvement in casualties' burns and traumatic tattoos was observed following debridement, aggressive scrubbing with or without dermabrasion, and conservative local dressing treatment protocol. The authors found a positive correlation between improvement degree and treatment timing. Injury pattern was correlative to the protective gear worn by the soldiers. Wearing protective eye gear and wearing ceramic vests can diminish the extent of IED injuries, while creating typical patterns of injuries to be treated. CONCLUSION: Based on these experiences, such injuries should be brought to a trauma center as soon as possible. Treating multidimensional trauma should be done in a facility with abilities to treat head injuries, eye injuries, penetrating injuries, blast injuries, and burns. Such specialized disciplines and facilities that have past experience with IEDs and war injuries are able to assess and treat these injuries in a more dedicated manner, resulting in better long-term rehabilitation. PMID- 26284375 TI - Deep Frostbite Treated With Hyperbaric Oxygen and Thrombolytic Therapies. AB - The authors present a case of deep frostbite treated with both hyperbaric oxygen and thrombolytic therapies. Both of these therapies are experimental and have not yet achieved widespread clinical use. The patient described in this paper sustained frostbite after becoming intoxicated and falling unconscious in a snowy field. He was treated acutely for hypothermia and came into the authors' care for wound management. Of his 6 digits with extensive, deep frostbite, 1 digit eventually required partial amputation, and another had protracted osteomyelitis treated with intravenous antibiotics. The authors present a case history in the context of current research and provide a listing of previous case reports of hyperbaric oxygen therapy for frostbite. PMID- 26284376 TI - Evaluation of Wound Healing Efficacy of an Antimicrobial Spray Dressing at Skin Donor Sites. AB - INTRODUCTION: Autologous skin transplantation is a common treatment for patients with full-thickness burns. Postoperative wound care is essential for skin graft donor and recipient sites, but traditional wound dressings such as cotton and gauze do not form an effective barrier to bacteria, and patients can feel uncomfortable when replacing dressings. MATERIALS AND METHODS: The goal of this study was to evaluate the use of an antimicrobial spray dressing (JUC Spray Dressing, NMS Technologies Co Ltd, Nanjing, China), with respect to its antimicrobial efficiency and the degree of pain experienced by patients. RESULTS: The authors found the antimicrobial spray can reduce pain during the recovery period, while providing equivalent antibacterial protection to the control treatment (AQUACEL Hydrofiber Wound Dressing, ConvaTec, Bridgewater, NJ) based on skin culture tests. The spray did not adversely affect the wound site recovery. No significant side effects were present during the treatment period. CONCLUSION: This antimicrobial spray could potentially be used in wound dressing applications. PMID- 26284377 TI - Evidence of Intensive Autolytic Debridement With a Self-Adaptive Wound Dressing. AB - BACKGROUND: Chronic venous leg ulcers (VLUs) can be challenging to manage and heal. Despite the observed efficacy of surgical debridement, many patients with VLUs refuse the procedure due to the associated pain. Autolytic debridement induces no pain, but is slow or disrupted in chronic VLUs. Elucidation of the wound dressing functions that are sufficient to support autolytic debridement is needed. MATERIALS AND METHODS: The authors report 2 challenging cases with large, nonresponsive VLUs. A 52-year-old female patient, Case 1, presented with a VLU of 91.4 cm(2) (10.5 cm x 8.7 cm); and a 58-year-old female patient, Case 2, presented with bilateral VLUs, the larger of which was 50 cm(2) (10 cm x 5 cm). Both VLU cases were covered with yellow slough, and case 1 had a small area of black necrotic tissue. The patients had received standard care for more than 16 months, but their VLUs were worsening. A self-adaptive wound dressing (SAWD) with a compression wrap was applied 2 to 3 times a week. RESULTS: Within 21 days, the VLUs of both cases had shed the yellow slough, and healthy granulation tissue was visible. CONCLUSION: In summary, the SAWD removed excess exudate with liquefied components of slough and nonvital tissue; provided sufficient moisture for preventing wound desiccation; sequestered microorganisms, thereby blocking their multiplication; and supported efficient autolytic debridement, clearing most of the slough and all crusted necrotic tissue within 3 weeks. The effect of SAWD on autolytic debridement is a promising mechanism for promoting healing of VLUs and warrants further study. PMID- 26284378 TI - Amputation? Surely Not! PMID- 26284379 TI - Hemophilia And Von Willebrand Disease In Children: Emergency Department Evaluation And Management. AB - Hemophilia and von Willebrand disease are the most common inherited bleeding disorders encountered in the emergency department. Evidence suggests that the management of bleeding disorders in the emergency department is currently suboptimal, and literature to guide evaluation and management in this setting is limited, though some guidelines do exist. The emergency clinician must have a high index of suspicion for new diagnoses, particularly in young patients with unprovoked bleeding and children with multiple or severe bleeds. The foundation of hemophilia treatment is urgent clotting factor replacement, with replacement goals guided by the presenting complaint. Bleeding in von Willebrand disease may be treated with products containing von Willebrand factor or with desmopressin. This review focuses on the epidemiology, pathophysiology, common presentations, evaluation strategies, and emergency management of these bleeding disorders. PMID- 26284380 TI - Cellulose-Templated Graphene Monoliths with Anisotropic Mechanical, Thermal, and Electrical Properties. AB - Assembling particular building blocks into composites with diverse targeted structures has attracted considerable interest for understanding its new properties and expanding the potential applications. Anisotropic organization is considered as a frequently used targeted architecture and possesses many peculiar properties because of its unusual shapes. Here, we show that anisotropic graphene monoliths (AGMs), three-dimensional architectures of well-aligned graphene sheets obtained by a dip-coating method using cellulose acetate fibers as templates show thermal-insulating, fire-retardant, and anisotropic properties. They exhibit a feature of higher mechanical strength and thermal/electrical conductivities in the axial direction than in the radial direction. Elastic polymer resins are then introduced into the pores of the AGMs to form conductive and flexible composites. The composites, as AGMs, retain the unique anisotropic properties, revealing opposite resistance change under compressions in different directions. The outstanding anisotropic properties of AGMs make them possible to be applied in the fields of thermal insulation, integrated circuits, and electromechanical devices. PMID- 26284381 TI - alpha-C-Glycosides via syn Opening of 1,2-Anhydro Sugars with Organozinc Compounds in Toluene/n-Dibutyl Ether. AB - The diastereoselective addition of organozinc species to 1,2-anhydro sugars in toluene/n-dibutyl ether solvent is reported. Compared to the existing methods, the reaction proceeds at 0 degrees C, and only a slight excess of nucleophile is required to achieve good yields. Scope was assessed with different O-protected glycals along with various nucleophiles (aryl, alkynyl). This methodology was applied to the synthesis of the alpha-anomer of canagliflozin. PMID- 26284382 TI - Identification of Protein-Protein Interactions by Detecting Correlated Mutation at the Interface. AB - Protein-protein interactions play key roles in a multitude of biological processes, such as de novo drug design, immune response, and enzymatic activity. It is of great interest to understand how proteins in a complex interact with each other. Here, we present a novel method for identifying protein-protein interactions, based on typical co-evolutionary information. Correlated mutation analysis can be used to predict interface residues. In this paper, we propose a non-redundant database to detect correlated mutation at the interface. First, we construct structure alignments for one input protein, based on all aligned proteins in the database. Evolutionary distance matrices, one for each input protein, can be calculated through geometric similarity and evolutionary information. Then, we use evolutionary distance matrices to estimate correlation coefficient between each pair of fragments from two input proteins. Finally, we extract interacting residues with high values of correlation coefficient, which can be grouped as interacting patches. Experiments illustrate that our method achieves better results than some existing co-evolution-based methods. Applied to SK/RR interaction between sensor kinase and response regulator proteins, our method has accuracy and coverage values of 53% and 45%, which improves upon accuracy and coverage values of 50% and 30% for DCA method. We evaluate interface prediction on four protein families, and our method has overall accuracy and coverage values of 34% and 30%, which improves upon overall accuracy and coverage values of 27% and 21% for PIFPAM. Our method has overall accuracy and coverage values of 59% and 63% on Benchmark v4.0, and 50% and 49% on CAPRI targets. Comparing to existing methods, our method improves overall accuracy value by at least 2%. PMID- 26284383 TI - Group Physical Activity Intervention for Childhood Cancer Survivors: A Pilot Study. AB - BACKGROUND: Inadequate physical activity (PA) in childhood cancer survivors may lead to compromised health outcomes. The purpose of this pilot study was to evaluate the feasibility and effect of a PA intervention in childhood cancer survivors ages 8-12 who report < 1 hour of moderate-to-vigorous physical (MVPA) per day. METHODS: Twenty survivors were randomized to a 6-month group PA intervention or to a control group. A pre/post measure of MVPA was completed by all participants, and a pre/post measure of self-efficacy was completed by the intervention group. Analysis included measures of feasibility, change in percentage of awake time spent in MVPA, self-efficacy scores, and correlations in MVPA and self-efficacy. RESULTS: All feasibility parameters were confirmed. Increases in percent of awake time spent in MVPA were seen in 67% of the intervention group and 14% of the control group. A medium effect size (r = 0.55) was calculated for the correlation between change in MVPA and change in total self-efficacy scores; the largest effect size (r = 0.62) was found for the subscale for adequacy. CONCLUSIONS: Increases in MVPA can be seen in childhood cancer survivors who participate in a group intervention that includes support of self-efficacy. PMID- 26284384 TI - Ligands Slow Down Pure-Dephasing in Semiconductor Quantum Dots. AB - It is well-known experimentally and theoretically that surface ligands provide additional pathways for energy relaxation in colloidal semiconductor quantum dots (QDs). They increase the rate of inelastic charge-phonon scattering and provide trap sites for the charges. We show that, surprisingly, ligands have the opposite effect on elastic electron-phonon scattering. Our simulations demonstrate that elastic scattering slows down in CdSe QDs passivated with ligands compared to that in bare QDs. As a result, the pure-dephasing time is increased, and the homogeneous luminescence line width is decreased in the presence of ligands. The lifetime of quantum superpositions of single and multiple excitons increases as well, providing favorable conditions for multiple excitons generation (MEG). Ligands reduce the pure-dephasing rates by decreasing phonon-induced fluctuations of the electronic energy levels. Surface atoms are most mobile in QDs, and therefore, they contribute greatly to the electronic energy fluctuations. The mobility is reduced by interaction with ligands. A simple analytical model suggests that the differences between the bare and passivated QDs persist for up to 5 nm diameters. Both low-frequency acoustic and high-frequency optical phonons participate in the dephasing processes in bare QDs, while low-frequency acoustic modes dominate in passivated QDs. The theoretical predictions regarding the pure dephasing time, luminescence line width, and MEG can be verified experimentally by studying QDs with different surface passivation. PMID- 26284385 TI - One-Dimensional Rod-Like Sb2S3-Based Anode for High-Performance Sodium-Ion Batteries. AB - Due to the high theoretical capacity of 946 mAh g(-1), Sb2S3 can be employed as promising electrode material for sodium-ion batteries (SIBs). Herein, the sodium storage behaviors of one-dimensional (1D) Sb2S3-based materials (Sb2S3 and Sb2S3@C rods) are successfully studied for the first time, displaying good cyclability and rate capability owing to their unique morphology and structure. Specifically, the Sb2S3@C rods electrode presents greatly enhanced electrochemical properties, resulting from the introduction of thin carbon layers which can effectively alleviate the strain caused by the large volume change and simultaneously improve the conductivity of electrode during cycling. At a current density of 100 mA g(-1), it delivers a high capacity of 699.1 mAh g(-1) after 100 cycles, which corresponds to 95.7% of the initial reversible capacity. Even at a high current density of 3200 mA g(-1), the capacity can still reach 429 mAh g( 1). This achievement may be a significant exploration for develpoing novel 1D Sb based materials or metal sulfide SIBs anodes. PMID- 26284387 TI - [Expression and significance of CMTM5 and epidermal growth factor receptor in prostate cancer]. AB - OBJECTIVE: To investigate the expression patterns of CKLF-like MARVEL transmembrane domain containing 5 (CMTM5), a novel tumor suppressor, and epidermal growth factor receptor (EGFR) in prostate cancer (PCa) tissues and cells and to analyze the relationship between CMTM5 and EGFR in PCa. METHODS: The expression patterns of CMTM5 and EGFR in PCa tissues and cells were detected by immunohistochemistry and Western blot, respectively. RESULTS: CMTM5 was highly expressed in 75% (27/36) of benigh prostatic hyperplasia (BPH) tissues but 35.9% (23/64) of PCa tissues (P<0.001). There was a significant difference of CMTM5 expression between the two groups of PCa tissues with different Gleason scores (P=0.003), though its expression was not related to the age, clinical stage, and metastatic situation (P>0.05). EGFR was highly expressed in 57.8% (37/64) of PCa tissues, it had statistical significance between EGFR and CMTM5 expressions in PCa tissues. Furthermore, 23 cases (35.9%) had low CMTM5 expression and high EGFR expression. Western blot showed that CMTM5 was undetectable in PCa cells, in which the EGFR expression was upregulated. CONCLUSION: The loss of CMTM5 may participate in the progression of PCa resulting from deregulated EGFR. PMID- 26284388 TI - [Mechanisms of prostaglandin E2-induced bone marrow-derived progenitor cell differentiation]. AB - OBJECTIVE: To identify the functions and mechanisms of prostaglandin E2 (PGE2) induced bone marrow-derived progenitor cells (BMPCs) maturation and its involved angiogenesis. METHODS: BMPCs harvested by flushing through the femoral and tibial bones and cultured. This population of cells was identified by immunofluorescence staining. From which, 1 MUmol/L PGE2 was taken, and quantitative-PCR (Q-PCR) and Western blot were used to detect the expressions of endothelial markers and Kruppel like factor 2 (KLF2) in BMPCs. In vitro tube formation assay was performed to demonstrate the capacity of angiogenesis. Furthermore, PGE2 and its receptors EP2 and EP4 agonists were used to elucidate the regulation of PGE2 to KLF2. RESULTS: C-kit, von Willebrand factor (vWF) and vascular endothelial cadherin expressed in BMPCs. Treatment with PGE2 (1 MUmol/L) significantly increased the differentiation of BMPCs. The mRNA levels of endothelial markers platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) and endothelial nitric oxide synthase (eNOS), were significantly upregulated in about 2 folds by PGE2 detected with Q-PCR assay. Matrigel tube formation assay also demonstrated PGE2 enhanced the ability of angiogenesis in BMPCs. In addition, the expression of KLF2 increased in more than 2 folds with PGE2 treatment compared with the control. Such effect of PGE2 could be blocked by EP4 blocking peptide. CONCLUSION: Promoting the differentiation of BMPCs, PGE2 reinforced their angiogenesis by binding to the receptor of EP4 in a KLF2-dependent manner. PMID- 26284389 TI - [Concentration of basic fibroblast growth factor in plasma and cavernous corpus of aged rat]. AB - OBJECTIVE: To investigate the concentration of basic fibroblast growth factor (bFGF) in aged rat plasma and penile tissues. METHODS: Twelve 24-month-old rats and ten 12-week-old rats were selected. We assessed the erectile responses of rats to cavernous nerve electrostimulation. Then the concentrations of bFGF in the rats' plasma and penile tissues were detected by ELISA kit and smooth muscle contents in the rats' cavernous corpus were evaluated by masson trichrome staining. RESULTS: Compared with the young rats, we found that the erectile function of the aged rats were significantly attenuated (The Max ICP/MAP in the aged rats were 0.41+/-0.05, 0.44+/-0.04 and 0.51+/-0.06 at 2.5 volts, 5.0 volts and 7.5 volts respectively while the Max ICP/MAP in the normal controls were 0.70+/-0.06, 0.75+/-0.07 and 0.81+/-0.04 at 2.5 volts, 5 volts and 7.5 volts respectively, P<0.05). The concentrations of bFGF [The bFGF levels in plasma and penile tissues in the aged rat were (6.43+/-0.51) MUg/L and (598.6+/-51.7) pg/mg protein respectively while the bFGF levels in the normal control were (10.53+/ 0.42) MUg/L and (985.8+/-76.8) pg/mg protein] were significantly reduced (P<0.05). Furthermore, the smooth muscle contents in the aged rats' penile tissues (0.038+/-0.005) were dramatically decreased compared with the normal control (0.075+/-0.006, P<0.05). CONCLUSION: The reduced levels of bFGF may be related to the decreased smooth muscle contents in the penile tissues of the aged rats. PMID- 26284390 TI - [A head-to-head comparison of contemporary indolent prostate cancer screen protocols in Chinese]. AB - OBJECTIVE: To compare the diagnostic accuracy of five internationally used indolent prostate cancer screen protocols in Chinese prostate cancer patients. METHODS: Retrospective analysis was made of the consecutive cohort of 314 patients, from Jan. 2006 to Apr. 2014, who had both prostate biopsy and radical prostatectomy in Peking University First Hospital. The Gleason score<=6, pT2, tumor volume<=0.5 mL, margin negative and lymph nodes negative were defined as indolent prostate cancer. The predictive value of five indolent screen criteria including Epstein, Memorial Sloan-Kettering Cancer Center (MSKCC), Prostate Cancer Research International: Active Surveillance (PRIAS), University of California, San Francisco (UCSF), and University of Miami (UM) were evaluated in Chinese prostate cancer patients. Measures of diagnostic accuracy and areas under the receiver-operating curve (AUC) were calculated for each protocol and compared. RESULTS: A total of 16% (49 cases) of the patients met the inclusion criteria of at least one protocol, including 24 cases in Epstein, 33 cases in MSKCC, 28 cases in PRIAS, 34 cases in UCSF, and 22 cases in UM. Three percent were eligible for all the studied criteria. UCSF and MSKCC protocols had the highest sensitivity and specificity than the others. The Epstein and PRIAS protocols demonstrated acceptable positive predictive value, but the specificity and sensitivity were inefficient. The UM protocol was performed unsatisfiedly on sensitivity, positive predictive value and AUC. A strict limited protocol which contained all the five protocols could not improve the predictive accuracy. CONCLUSION: The UCSF protocol had better diagnostic accuracy than the others, but the results were not satisfied. A further investigation on indolent prostate cancer screening in Chinese patients is needed. PMID- 26284391 TI - [Predictor analysis of PSA response of docetaxel combined with prednisone in the treatment of metastatic castration resistant prostate cancer]. AB - OBJECTIVE: To investigate the factors that may predict the effectiveness of metastatic castration resistant prostate cancer (mCRPC) patients who received docetaxel plus prednisone treatment. METHODS: We retrospectively collected the clinical data of mCRPC patients who has received docetaxel chemotherapy in Peking University First Hospital between February 2010 and March 2015, and the clinical factors were analyzed using univariate analysis. RESULTS: A total of 60 cases of patients were treated, of whom 33 with complete clinical data were analyzed. PSA responsive was defined as PSA declining >=50% of baseline and without progression according to RESCIST criteria. The median PSA at chemotherapy was 153.4 MUg/L (6.6-9 952.0 MUg/L), and a total of 20 cases (60.6%) were PSA responsive. Univariate analysis found that lower Gleason score (Gleason scores<=7) (25% vs.72%, P=0.034), the existence of positive Lymph node (78% vs. 40%, P=0.032), the existence of visceral metastasis (80% vs. 44%, P=0.041) and baseline blood HGB value<=120 g/L (30% vs. 74%, P=0.024) were associated with chemotherapy effectiveness. CONCLUSION: High Gleason score, lymph node metastasis, visceral metastasis and normal HGB level may predict PSA response after docetaxel-based chemotherapy. PMID- 26284392 TI - [Efficacy and outcome of palliative TURP in patients with bladder outlet obstruction induced by advanced prostate cancer]. AB - OBJECTIVE: To evaluate the efficacy and outcome of palliative transurethral resection of the prostate (pTURP) in patients with server bladder outlet obstruction (BOO) due to prostatic obstruction induced by advanced prostate cancer. METHODS: All the 16 patients who had a pTURP between November 2007 and January 2015 due to BOO (high residual urine volume combined with hydronephrosis or urinary retention refractory to medical treatment) at our institution were retrospectively assessed. All the patients were diagnosed with advanced prostate cancer (III stage or IV stage). The clinical data, functional and oncological follow-up results were evaluated. The cancer specific survivals were estimated by Kaplan-Meier analysis. RESULTS: The mean age of the patients was 73.8 years (63 81 years). Five cases were graded in stage III of prostate cancer and 11 in stage IV. The indications for pTURP were refractory urinary retention in 12 cases, and high residual urine volume with hydronephrosis in 4 cases. The mean prostate volume at pTURP was 43.2 mL (28-78 mL) and the mean PSA (prostate specific antigen) level before pTURP was 48.2 MUg/L (2-107 MUg/L). The patients had mean residual urine volume 166.4 mL (50-450 mL) and mean urinary flow rate 3.6 mL/s (0 6 mL/s, n=7) before pTURP. It took mean 62.9 min (35-94 min) in pTURP with mean estimated blood loss 126.9 mL (30-263 mL) and mean resected tissue 14.1 g (10-22 g). There were no transfusion cases. Postoperative mean serum PSA 20.5 MUg/L (1 41 MUg/L), residual urine volume 43.4 mL (0-400 mL) and urinary flow rate 10.1 mL/s (7-16 mL/s, n=7) were shown in these cases. A patient encountered persistent hematuria needing irrigation. Compared with preoperation, the patients had significantly lower serum PSA level (P<0.001), less residual urine volume (P<0.001) and more urinary flow rate (P=0.001) after pTURP. The mean follow-up after pTURP was 36 months (1-86 months). In addition, 2 patients received repeated pTURP. At the time of the latest analysis, 3 patients died from prostate cancer progression. As estimated by Kaplan-Meier analysis, the 2-, 3- and 5-year cancer specific survival rates after pTURP were 91%, 78% and 58%, respectively. CONCLUSION: Despite less resected tissue, greater delay in urination and reoperation rates, pTURP is a fairly effective procedure in patients with server BOO. Although a potential negative impact of pTURP on survival cannot be excluded, the estimated 3- and 5-year cancer specific survival rates in this series seem to justify this intervention. PMID- 26284393 TI - ["Sandwich" urethra reconstruction improves the early continence following laparoscopic radical prostatectomy]. AB - OBJECTIVE: To explore the safety and efficacy of "sandwich" urethra reconstruction in laparoscopic radical prostatectomy (LRP) for the early recovery of continence. METHODS: LRP was performed using a urethra surrounding tissue reconstruction in 37 consecutive patients, and without reconstruction procedure in 34 consecutive patients at the same period from March 2012 to January 2013. The baseline data, preoperative data: The patient age, body mass index (BMI, kg/m2), International prostate symptoms score (IPSS), prostate volume, preoperative PSA, Gleason score were assessed retrospectively; Operative data: The neurovascular bundle preservation, operation time, blood loss were assessed; and the primary outcome measure was urinary continence assessed at the end of 1, 2, 4, 12 and 24 weeks after the catheter was removed. Other data recorded were duration of indwelling catheter, positive margin rate and complications. RESULTS: There were no significant differences between the two groups with respect to baseline,preoperative and operative data except of the operative time (P=0.003). Between the two groups, the continence of the reconstruction group was higher than that of the control group at the end of 4 and 12 weeks (P=0.007, P=0.020, respectively). CONCLUSION: Urethra surrounding tissue reconstruction in LRP is safe and feasible, and it could improve early recovery of continence. PMID- 26284394 TI - [Prognostic factors for intravesical recurrence after surgery for upper tract urothelial carcinoma in renal transplant recipients]. AB - OBJECTIVE: To elucidate clinicopathological independent prognostic factors for intravesical recurrence after nephroureterectomy for native upper tract urothelial carcinoma (UTUC) in renal transplant recipients. METHODS: In this study, 38 patients clinically diagnosed as localized UTUC after renal transplantation were included, and treated by retroperitoneal laparoscopic nephroureterectomy between April 2006 and March 2013, after exclusion of those with a previous and/or concurrent history of bladder cancer. The clinicopathologic features, risk factors, and intravesical recurrence free survival were analyzed using the Kaplan-Meier method. Univariate and multivariate analyses by Cox's proportional hazards regression model were used to identify independent risk factors for intravesical tumor recurrence. RESULTS: Of all the patients, 16/38 (42.1%) developed subsequent intravesical recurrence during a median follow-up period of 38 months (range 12 to 104 months), of whom, 12/16 (75.0%) developed recurrent bladder cancer within 2 years after nephroureterectomy, and the median interval between surgery and intravesical recurrence was 15.5 months (range 6 to 48 months). Multifocal tumors, native aristolochic acid nephropathy (AAN) and distal ureter involvement were determined as risk factors for intravesical recurrence by univariate analysis. The intravesical recurrence rate was 62.5% (5/8) in the group of native AAN, and 46.2% (12/26) in the group of multifocality. By multivariate analyses, multifocality (HR=2.603, 95% CI=1.529-8.906, P=0.019) and native AAN (HR=2.179, 95% CI=1.085-8.093, P=0.038) were identified as independent predictors for the development of recurrent bladder cancer after surgery for UTUC in renal transplant recipients. CONCLUSION: The incidence of intravesical recurrence after laparoscopic nephroureterectomy for UTUC in renal transplant recipients is high, and most subsequent bladder cancers recur within 2 years after surgery. Tumor multifocality and native AAN are significant independent risk factors in developing initial intravesical recurrence after laparoscopic surgery for primary UTUC after renal transplantation. PMID- 26284395 TI - [Treatment of local low/intermediate risk prostate cancer with low dose rate brachytherapy: a report of 133 cases at a single center]. AB - OBJECTIVE: To investigate the safety and efficacy of low dose rate brachytherapy in local low and intermediate risk prostate cancer patients. METHODS: All 133 local prostate cancer patients were included and divided into low and intermediate risk groups respectively according to Memorial Sloan Kettering Group (MSKG) definition followed by brachytherapy. All the data including prostatic specific antigen (PSA), international prostatic symptomatic score (IPSS), post operation complications and image evaluation were collected and recorded. RESULTS: The average radiation dose delivered to 90% of the prostate (D90) of (152.0+/-17.3) Gy was performed in the patients with a mean pre-operation PSA level of (13.45+/-7.1) MUg/L and prostate volume of (44.37+/-21.43) mL. Neoadjuvant therapy was performed in 24 patients with prostate volume larger than 60 mL for 3-6 months. There was no difference in the mean age, prostate volume and D90 between low risk group and intermediate risk group. The mean IPSS reached its peak at the end of the 2nd month post-brachytherapy and compared with the baseline at the end of the 4th month. PSA failure occurred at the end of the mean 31.7 months in 4 patients during the follow-up (1 in low risk group and 3 in intermediate risk group) and no metastasis occurred. CONCLUSION: Lower urinary tract symptom (LUTS) is the most common complication post-operation. Brachytherapy associates with an encouraging tumor progress-free survival in local low and intermediate risk prostate cancer patients. PMID- 26284396 TI - [Treatment of upper urinary calculi through novel modular flexible ureteroscope: a report of 36 cases]. AB - OBJECTIVE: To evaluate the feasibility and efficacy of novel modular flexible ureteroscope in the treatment of upper urinary calculi. METHODS: From Nov. 2013 to Jul. 2014, 36 cases of upper urinary calculi were treated with holmium laser lithotripsy through novel modular flexible ureteroscope. The clinical data including the location and diameter of the calculi, time of operation, stone-free rate, complications and hospital stay after operation were analyzed retrospectively. RESULTS: The operation was performed successfully in 34 cases, the average time of operation was 108.5 min (70-145 min), the post-operation hospital stay was 2-5 d (average 2.3 d), and the stone-free rate was 83.33%. No serious complications occurred except postoperative fever in 2 cases and haemorrhage in 1 case. CONCLUSION: The novel modular flexible ureteroscope is a safe and effective medical instrumentation for treatment of upper urinary calculi. PMID- 26284397 TI - [Management of calyceal diverticular calculi with stenotic infundibulum by flexible ureteroscopic holmium laser infundibulectomy and lithotripsy]. AB - OBJECTIVE: To evaluate the efficacy and safety of flexible ureteroscopic holmium laser lithotripsy in treating calyceal diverticular calculi with stenotic infundibulum and to present our initial experience. METHODS: From Nov. 2012 to Nov. 2014, 10 patients with stone-bearing calyceal diverticulum and stenotic infundibulum underwent flexible ureteroscopic holmium laser lithotripsy in our hospital, including 3 female patients and 7 male patients with an average age of 36.9 years (range: 20 to 62 years). There were 6 patients with right side while 4 patients with left side calyceal diverticular calculi. The average cumulative stone size was (1.33+/-0.43) cm. Five patients underwent extracorporeal shock wave lithotripsy (ESWL) before hospital admission but no stone was discharged. All the patients received intravenous urography (IVU) and CT-urography (CTU) preoperatively and underwent double-J stents placement 2 weeks before operations. A digital-fiber flexible ureteroscopy and 200 MUm holmium laser fiber were used for treatment. Surgeries began with routine flexible ureteroscopy and methylene blue injection was used to identify the small ostium of infundibulum. Then infundibulectomy followed by lithotripsy was performed. All the patients receive double-J stents placement and traditional Chinese medicine for 1 to 3 months after operations. The stone clearance was estimated by kidney ureter bladder (KUB) within 3 months' follow up. RESULTS: The locations of calyceal diverticulum were upper pole in 7 patients, and interpolar regions in 4 patients. The average operation time was (123.7+/-59.6) min, and the average estimated blood loss was (29.3+/-32.1) mL. Successful flexible ureteroscopic holmium laser infundibulectomies were performed in all the 10 patients. Success rate was 100%. The stone clearance rates for 1 and 3 months after surgery were 50.0% and 80.0%, respectively, which were observed by KUB follow-up. Two patients had serious post operative fever (>38.0 degrees C) in coexistence with chills. The mobidity of urosepsis was 20.0%. No major complications were identified. CONCLUSION: In selected patients, calyceal diverticular calculi with stenotic infundibulum can be treated safely and efficiently with flexible ureteroscopic homium laser lithotripsy. CTU and IVU should be completed preoperatively for calyceal diverticulum location and technique difficulty prediction. Retrograde methylene blue injection can be used to identify the ostium during surgery. And prolonged post-operation stone clearance was observed. PMID- 26284398 TI - [Clinical characteristics of IgG4 related retroperitoneal fibrosis: a report of 5 cases and literature review]. AB - OBJECTIVE: To explore the clinical characteristics, treatment and prognosis of IgG4-related retroperitoneal fibrosis (RPF). METHODS: All the patients diagnosed as RPF in Peking University People's Hospital between February 2008 and October 2014 were included. Among them, 5 patients were identified as IgG4 related RPF. We analyzed their medical records and summarized the clinical, laboratory, and imaging features of IgG4 related RPF, which had taken the recent literature into account. RESULTS: All the 5 patients were male, with the average age 62.2 years (55-67 years). They mainly complained of abdominal pain, flank pain and weight loss, two of whom had concurrent antoimmune pancreatitis. Renal insufficiency was present in 3 patients (3/5). Four patients (4/4) showed increased erythrocyte sedimentation rate (ESR), while 3 patients (3/4) had higher serum C-reactive protein (CRP) and IgG. In addition, 4 patients (4/4) had significantly elevated serum IgG4 level. On computed tomography (CT) imaging, 5 patients showed retroperitoneal mass which surrounded the abdominal aorta and the iliac arteries, and even enveloped the ureters and the inferior vena cava. Only one patient received tissue pathological examination, which indicated the numbers of IgG4 positive plasma cells per high power field>10 and a ratio of IgG4-positive cells to all IgG-bearing cells>40%. One patient received simple surgical intervention, and 1 patient received medical treatment alone, while the remaining 3 patients received combined treatment of surgery and medications. follow-up was available for the 4 patients, all of whom had good prognosis. CONCLUSION: Part of RPF was actually IgG4-related, which was also nominated as IgG4 related RPF. It was a rare disease with unknown etiology, characterized by the elevated serum IgG4 concentration (>=1.35 g/L), with marked tissue infiltration by lymphocytes and IgG4-positive plasma cells with fibrosis, in addition to the presence of retroperitoneal mass. Glucocorticoids were the first-line therapy and IgG4 related RPF had a favourable prognosis. PMID- 26284399 TI - [Risk factors for the development of postoperative paralytic ileus after radical cystectomy: a report of 740 cases]. AB - OBJECTIVE: To identify the risk factors that would aid in the identification of patients at the greatest risk of developing postoperative paralytic ileus. METHODS: In the retrospective study, 749 patients who received radical cystectomy from January 2005 to August 2014 were reviewed, of whom, 9 who received orthotopic ileal neobladder were excluded. Of the 740 patients, 82 (11.1%) developed postoperative paralytic ileus. The correlation between the clinical characters and the occurrence of post-operative paralytic ileus was identified. RESULTS: The postoperative paralytic ileus was significantly correlated with the patient's age (68 vs. 67, P=0.025), body mass index (23.0 kg/m2 vs.24.1 kg/m2, P=0.008), different urinary diversion reconstruction methods [13.2% (66/500) for ileal conduit and 7.3%(16/240) for cutaneous ureterostomy, P=0.008] and pelvic lymph node dissection [12.2% (77/632) vs.4.6% (5/108), P=0.021].The postoperative paralytic ileus caused a prolonged hospital stay and delayed recovery (24 d vs. 17 d, P=0.000). There was no significant correlation between the postoperative paralytic ileus and the patients' gender, previous abdominal operations, preoperative hemoglobin and creatinine, American Society of Anesthesiologists score, operative time, estimated blood loss, transfusion requirement, laparoscopic and open surgery, ICU admission or tumor staging. On multivariate analysis, age (hazard ratio 1.185, 95% confidence interval 1.036-1.355, P=0.013), body mass index (hazard ratio 0.605, 95% confidence interval 0.427-0.857, P=0.005), different urinary diversion reconstruction methods (hazard ratio 2.422, 95% confidence interval 1.323-4.435, P=0.004) and pelvic lymph node dissection (hazard ratio 2.798, 95% confidence interval 1.069-7.322, P=0.036) were significantly correlated with the presence of the postoperative paralytic ileus. CONCLUSION: Increasing age, decreasing BMI, ileal conduiturinary diversion and pelvic lymph node dissection were significantly correlated with the presence of postoperative paralytic ileus in patients undergoing radical cystectomy. PMID- 26284400 TI - [Percutaneous "sandwich" endopyeloplasty technique: a new endourological measure for ureteropelvic junction obstruction]. AB - OBJECTIVE: To report a new endourological technique-percutaneous "sandwich" endopyeloplasty for ureteropelvic junction obstruction (UPJO). METHODS: In the study, 71 patients with UPJO had endopyeloplasty by percutaneous balloon dilation before and after endopyelotomy, so called "sandwich" endopyeloplasty. The ureter stent was removed after 2 months and all the patients were followed up at least 12 months by ultrasound, intravenous urogram (IVU) or renal scintigraphy. RESULTS: There were 12 patients with primary UPJO, and 59 patients with iatrogenic UPJO after pyelolithotomy, pyeloplasty, ureteroscopic lithotripsy or percutaneous nephrolithotomy. The mean length of stricture was (1.4+/-0.8) mm while 5 cases had complete stenosis ureteropelvic junction (UPJ). The mean glomerular filtration rate (GFR) of the affected kidney was (19.8+/-10.8) mL/min.69 patientshad one-stage operation successfully and 2 patients with complete UPJ stenosis were recanalized in the secondary procedures. The mean time of the operation was (39.3+/-24.2) min. The complications included 1 case of hemotoma, and 2 cases with residual stones. In the follow-up period, 7 patients were re-obstructed. CONCLUSION: Percutaneous "sandwich" endopyeloplasty shows good results for UPJO of selected patients with simple operation, minimal invasiveness, quick recovery and few severe complications. PMID- 26284401 TI - [Efficiency evaluation of diuretic renography in the operative or conservative treatments of unilateral ureteropelvic junction obstruction patients]. AB - OBJECTIVE: To analyze the efficiency of diuretic renography in the management of unilateral ureteropelvic junction obstruction (UPJO) patients, by observing the affected kidney relative renal function (RRF) and drainage in the period of follow-up. METHODS: In the study, 76 patients diagnosed as unilateral UPJO were retrospectively collected. Diuretic renography was performed on all the patients initially, and during the period of follow-up. No morphological or functional abnormalities were detected on the contralateral kidney. Changes of affected renal RRF and drainage were observed during the follow-up period. The correlations of initial RRF (RRFinitial) and drainage type with RRF improvement were analyzed. RESULTS: In the operative group (57 cases), the RRFinitial of affected kidney was 40.81%+/-12.96%, and the RRF in the last follow-up (RRFrecent) was 44.63%+/-13.21% (P<0.05). Drainage improvements was found in 54.00% of the obstructive patients (27/50), and unchanged in 71.43% of the non obstructive patients (5/7). In the conservative group (19 cases), the RRFinitial was 46.47%+/-12.84%, and the RRFrecent was 46.95%+/-11.86% (P>0.05). One obstructive patient (1/10) was found with improved drainage, and the other 9 obstructive patients (9/10) and all of the non-obstructive patients (9/9) were observed with unchanged drainage. Four patients with deteriorated RRF in the conservative group received surgery. There were no significant differences in the changes of affected renal RRF in different RRFinitial and drainage types in both operative and conservative groups. CONCLUSION: Diuretic renography could be effectively applied in the follow-up of unilateral UPJO patients. Operation could improve affected kidney's RRF, and better some patients' drainage conditions. However, for those patients with no or minor clinical symptoms, conservative management could be accepted if RRF remains stable during the period of follow up. PMID- 26284402 TI - [Ileal ureteric replacement for iatrogenic long segment ureteric injuries]. AB - OBJECTIVE: To investigate the efficacy of ileal ureteric replacement in the treatment of iatrogenic long segment ureteric injuries. METHODS: The hospital records of 9 cases with iatrogenic long segment ureteric injuries during Aug. 2010 to Sept. 2014 treated with ileal ureteric replacement were retrospectively reviewed and followed-up postoperatively. The patients included 3 males and 6 females with a median age of 40 years. The length of injury segment was 13-25 cm (median 20 cm). The etiology of the iatrogenic injury was urological surgery (n=6), gynecological surgery (n=2) and general surgery (n=1), respectively. The ureter stent was removed in 1-2 month postoperatively in all the 9 cases. RESULTS: All the operations were successful. The operation time was 203-394 min, with the average of (278.1+/-68.8) min. The bleeding volume was 10-1 000 mL, with the median of 200 mL. The mean length of hospital stay was (16.8+/-7.5) days. Four minor complications (Grade I-II) developed, including 3 ileus (33.3%) and 1 proximal anastomotic leakage (11.1%). The median follow-up time was 11 months, serum creatinine decreased or remained stable in 8 patients (88.9%). Three patients (33.3%) developed mild hydronephrosis and short-time urinary tract infection was seen in 1 patient (11.1%). Metabolic acidosis was not detected during the follow-up. CONCLUSION: Ileal ureteric replacement is a safe and effective method in patients with complex or difficult iatrogenic long segment ureteric injuries. PMID- 26284403 TI - [Application of scrotoscope in the diagnosis and treatment of testicular and epididymal diseases]. AB - OBJECTIVE: To evaluate the safety and efficacy of scrotoscope in diagnosis and treatment of testicular and epididymal diseases. METHODS: From September 2010 to March 2012, a total of 75 patients, aged 15-64 years (mean age is 42.4 years) were included in this study. Based on ultrasonagraphy before surgery, 12 cases were diagnosed as testicular torsion and 63 cases were diagnosed as epididymal mass. All the patients underwent scrotoscope examination or scrotoscope epididymectomy. A small scrotal incision of 1.0 cm was performed. Bluntly dissection was then performed through the scrotal layer until the tunica sac was disclosed. We used cystoscope or resectoscope as scrotoscope. Keeping the drip fusion of isotonic solution inflowing, the scrotum was maintained appropriate distended. The tunica sac wall including parietal and visceral tunica was checked. The testis, epididymis was then examined from the anterior, posterior and both lateral aspects to find out any potential pathology. The operation time of scrotoscope, postoperative complications, surgery record, ultrasound and pathology results were collected from medical record. Visual analog pain scale (range from 0 points to 10 points, 0 represent no pain, 10 represent the most severe pain) was used to assess scrotal pain. The postoperative complications, recurrence and pain relief were evaluated, the accuracy rates of the diagnosis was compared between scrotoscope and ultrasound based on pathology results. RESULTS: All the patients were successfully performed scrotoscope except one because of inflammatory adhesion. The average time of the operation was 34.3+/ 5.8 minutes, and no serious complications, such as severe edema, hematoma, testicular hydrocele and wound infection occurred. The accuracy rate of scrotoscope and ultrasound for the diagnosis of testicular torsion was 100% vs. 66.7%, and the accuracy rate of scrotoscope and ultrasound for the diagnosis of epididymal mass was 76.2% vs. 58.7%. In the study, 63 patients received scrotoscope epididymectomy, the visual analogue pain score before surgery was 7.1+/-0.8, 6 months after operation, and the pain score was 2.4+/-0.6. CONCLUSION: Scrotoscope is safe. There are no serious complications such as severe edema, hematoma, testicular hydrocele and wound infection occurred. Scrotoscope is superior to ultrasound for diagnosis of testicular torsion and epididymal mass. Scrotoscope epididymectomy is effective for pain relief, especially for patients with epididymal cyst. PMID- 26284404 TI - [Detection of cytochrome P450 3A4 gene polymorphism guides for labor analgesia with sufentanil medication]. AB - OBJECTIVE: To investigate the relationship between single nucleotide polymorphisms (SNPs) of cytochrome P450 (CYP450) 3A4 rs2242480 and inter individual differences of sufentanil consumption in accouchement sans douleur. METHODS: A total of 131 parturient women were collected. According to the distribution of genotypes and allele frequencies of rs2242480, the doses of sufentanil were individually designed. CC homozygotes were given the standard analgesia dose, CT heterozygotes and TT homozygotes were given 87.6% of standard sufentanil dose. RESULTS: Visual analogue score (VAS) between CC group and CT/TT group were 3.67+/-1.2 and 3.44+/-1.5, consistent with the expected analgesic standards. The difference was not statistically significant. CONCLUSION: The parturient women carrying CT heterozygotes and TT homozygotes of CYP3A4 rs2242480 required less sufentanil in accouchement sans douleur. PMID- 26284405 TI - [Clinical characteristics and treatment outcomes of microscopic polyangiitis combined with autoimmune hemolytic anemia]. AB - OBJECTIVE: To investigate the clinical characteristics, laboratory features, outcome and prognosis of microscopic polyangiitis (MPA) patients with autoimmune hemolytic anemia (AIHA). METHODS: In this study, 63 cases diagnosed as MPA from October 2006 to November 2013 in Peking University People's Hospital were reviewed. The clinical characteristics, outcome and prognosis of MPA patients with AIHA were retrospectively analyzed. RESULTS: There were 12.7% (8/63) MPA patients with AIHA. The patients with AIHA had higher prevalence of fever, fatigue, hematuresis, albuminuria and new-onset hypertension, compared with non AIHA group(87.5% vs.29.1%;100% vs. 49.1%; 100% vs. 60%; 75% vs. 20%, all P<0.05). In patients with AIHA, there were significantly lower levels of red blood cell(RBC), hemoglobin(Hb), alanine albumin(Alb) and complement C3[(2.3+/ 0.5)*10(12)/L vs.(3.0+/-0.7)*10(12)/L;(66.2+/-13.1) g/L vs.(90.0+/-20.3) g/L; (26.1+/-4.4) g/L vs. (33.5+/-6.4) g/L; (0.7+/-0.2) g/L vs.(0.9+/-0.3) g/L,all P<0.05]. However, the levels of erythrocyte sedimentation rate (ESR), IgG and Birmingham Vasculitis Activity Score (BVAS) were higher, compared with those in the patients without AIHA [(102.1+/-25.7) mm/1 h vs.(76.5+/-31.1) mm/1 h; (20.9+/ 6.1) g/L vs. (14.5+/-6.0) g/L; ( 23.7+/-5.7) vs.(17.3+/-4.1), all P<0.05]. The study suggested that there were more severe multi-system damage in the patients with AIHA than in those without AIHA. In the MPA patients with AIHA, six cases received treatment of methylprednisolone combined with immunosuppressant, and two received treatment of methylprednisolone only. Among the eight cases, three were recovered from anemia and four improved. One died of severe lung infection. After 4 years follow-up,in the seven MPA patients with AIHA, three received remission, two died,and two suffered from anemia and abnormal renal function. CONCLUSION: MPA with AIHA is more complicated by multi-system damage and not rare in clinical settings. Glucocorticoid combined with immunosuppressant is beneficial to induce remission for MPA patients with AIHA. PMID- 26284406 TI - [Experimental study of dendritic cells transfected with cancer stem like cells RNA against 9L brain tumors]. AB - OBJECTIVE: To investigate the anti-tumor efficacy of dendritic cells (DC) vaccination transfected with total RNA of cancer stem like cells and to discuss the mechanism of immune response, so as to provide experimental basis for clinical application. METHODS: Dendritic cells were isolated from F344 bone marrow cells, then these dendritic cells were transfected with total RNA of 9L cancer stem cells or 9L monolayer cells. F344 rats bearing with 9L brain tumors were treated by subcutaneous injection of either PBS, unpulsed DC, DC transfected with 9L monolayer cells RNA (DC-9LTS) or DC transfected with 9L tumor spheres RNA (DC-9L)3, 10, 17. And 21 days after tumor implantation, the brains and sera were obtained from the different groups, the lymphocytes infiltration was detected by immunohistochemistry, and the concentration of interferon-gamma (IFN-gamma) was tested by ELISA. The survival time was observed and determined using the method of Kaplan Meier analysis. RESULTS: The rats vaccinated with DC transfected with 9L tumor spheres RNA (DC-9LTS) and the monolayer cell RNA (DC-9L) expired with median survival time of 36 and 31 days, respectively. The animals bearing intracranial 9L gliosarcoma were vaccinated with un-pulsed DC vaccine, all expired with a median survival time of 21 days. The Kaplan-Meier survival curve showed that the rats treated with DC-9LTS had longer survival than the other groups (P<0.01). There was significant difference among DC-9L group, DC group, and PBS group (P<0.01). There was no significant difference between DC group and PBS group (chi2=0.071, P=0.789).The concentration of IFN-gamma of DC-9LTS group [(157.08+/-7.25) ng/L] was much higher than those of the other groups (P<0.05). DC-9LTS could effectively enhance T-cell infiltration, a large number of CD8+ cells were detected in and around the tumor in DC-9LTS group, compared with DC-9L group, DC and PBS group (P<0.001). The expression of CD8+ cell was not detected in DC group and PBS group. However no expression of CD4+ cells was observed in all the groups. CONCLUSION: Immunotherapy using DC transfected with 9L CSLCs total RNA was more effective for the treatment of 9L brain gliomas, and the strategy prolonged the survival of 9L glioma-bearing rats significantly, which provides a scientific foundation for further investigation of this approach to eradicate gliomas. PMID- 26284407 TI - [Diffusion of fluorescent and magnetic molecular probes in brain interstitial space]. AB - OBJECTIVE: To compare the diffusion properties of fluorescent probes dextran tetramethylrhodamine (DT) and lucifer yellow CH (LY) and magnetic probe gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) in porous media and to screen out a suitable fluorescent probe for optical imaging of brain interstitial space (ISS). METHODS: Agarose gels sample were divided into DT group, LY group and Gd-DTPA group, and the corresponding molecular probes were imported in each group. The dynamic diffusions of DT and LY in agarose gels at different time points (15, 30, 45, 60, 90, and 120 min) were scanned with laser scanning confocal microscope, the dynamic diffusion of Gd-DTPA was imaged with magnetic resonance imaging. The average diffusion speed of LY were demonstrated to be consistent with those of Gd-DTPA. The LY was introduced into caudate putamen of 18 rats, respectively, the diffusion of LY in the sequential slices of rat brain at different time points (0.5, 1, 2, 3, 7, 11 h) were scanned, and the results were compared with those of rats' brain with Gd-DTPA imported and imaged in vivo with magnetic resonance imaging. RESULTS: The diffusions of the three probes were isotropic in the agarose gels, and the average diffusion speeds of DT, LY and Gd DTPA were: (0.07+/-0.02)*10(-2) mm2/s, (1.54+/-0.47)*10(-2) mm2/s, (1.45+/ 0.50)*10(-2) mm2/s, respectively. The speed of DT was more slower than both LY and Gd-DTPA (ANOVA, F=367.15, P<0.001; Post-Hoc LSD, P<0.001), and there was no significant difference between the speeds of LY and Gd-DTPA (Post-Hoc LSD, P=0.091). The variation tendency of diffusion area of DT was different with both that of LY and that of Gd-DTPA (Bonferroni correction, alpha=0.0125, P<0.001), and there was no significant difference between LY and Gd-DTPA (Bonferroni correction, alpha=0.0125, P=0.203), in analysis by repeated measures data of ANOVA. The diffusions of LY and Gd-DTPA were anisotropy in rat caudate putamen,and the average diffusion speeds of LY and Gd-DTPA were: (1.03+/ 0.29)*10(-3) mm2/s, (0.81+/-0.27)*10(-3) mm2/s, respectively, no significant difference was demonstrated (t=0.759, P=0.490); half-time of single intensity of LY and Gd-DTPA was (2.58+/-0.04) h, (2.46+/-0.10) h, respectively, no significant difference was found (t=2.025, P=0.113). The diffusion area ratios between LY and Gd-DTPA in rat caudate putamen was not statistically different at hours 0.5, 1, 2, 3 and 7 (t=2.249, P=0.088; t=2.582, P=0.061; t=1.966, P=0.121; t=0.132, P=0.674; t=0.032, P=0.976), while, a slightly difference was found at 11 h (t=2.917, P=0.043,in analysis by t test). CONCLUSION: LY present the same diffusion property with Gd-DTPA in porous media witch including agarose gels and live rat brain tissue, indicates that LY is a suitable fluorescent probe for optical imaging of brain ISS, and it can be used for microscopic, macro and in vitro measure of brain ISS. PMID- 26284408 TI - [Effects of sevoflurane on brain neuroapoptosis and ability of long-term learning and memory in newborn rats]. AB - OBJECTIVE: To investigate the changes of neuroapoptosis in brain and learning ability after neonatal mice are exposed to inhaled sevoflurane. METHODS: Twenty one postnatal day (P) 7 Wistar rats were randomly divided into 7 groups for the preliminary experiment. Arterial blood samples were obtained immediately at the end of anesthesia, then blood analysis was performed. According to the results of the blood analysis, the groups that had no carbon dioxide accumulation were chosen for the following experiment. Ninety postnatal day (P) 7 Wistar rats were randomly divided into 5 groups: group A [sham anesthesia], group B [1% (volume fraction) sevoflurane for 2 h], group C (1% sevoflurane for 4 h), group D [2% (volume fraction) sevoflurane for 2 h] and group E (2% sevoflurane for 4 h). The animals from each group were perfused transcardially with 0.1 mol/L phosphate buffer containing 4% (volume fraction) paraformaldehyde 6 h after the end of anesthesia, and then the brains were exposed for immunohisochemistry, and caspase 3 positive cells were detected. Behavioral studies which included Morris water maze and passive voidance test were performed separately when the rats were 5 week-old, 8-week-old and 14-week-old. RESULTS: The blood gas data in the mice during the anesthesia showed that the pH, arterial carbon dioxide tension, arterial oxygen tension, and arterial oxygen saturation did not differ significantly from those of the sham controls. The amount of the caspase-3 positive cells in the rat brains of group B, group D and group E was greater than that in group A. When facing the spatial reference memory task or space exploration task, the rats from the different groups made it uniformly. The rats exposed to sham anesthesia had longer latency and less mistake times than those to sevoflurane in passive voidance test when they were 5-week-old, while all the rats had no significant difference in 8 weeks. CONCLUSION: Exposure to the concentration of 2% sevoflurane causes brain cell apoptosis of newborn rats. The memory ability to pessimal stimulation is decreased as the anesthesia mice were 5 week-old, such changes recede along with the growth of the rats. Exposure to the concentration of 2% sevoflurane does not affect the spatial reference memory of newborn rats during their growth. PMID- 26284409 TI - [Surgical treatment of paraclinoid aneurysms]. AB - OBJECTIVE: To explore the surgical treatment of paraclinoid aneurysms and evaluate the safety and efficacy of microsurgical clip and endovascular embolization of paraclinoid aneurysms. METHODS: The data of 28 patients with 30 paraclinoid aneurysms receiving surgical treatment were retrospectively analyzed. According to Barami classification, 4 aneurysms were type Ia, 5 aneurysms type Ib, 13 aneurysms type II, 4 aneurysms type IIIa, 1 aneurysm type IIIb, and 3 aneurysms type IV. In the study, 15 cases with 17 paraclinoid aneurysms received microsurgical treatment, of which 3 cases underwent superficial temporal artery middle cerebral artery (STA-MCA) bypass firstly and then aneurysms were trapped. The other 13 cases received endovascular embolism, in which balloon assistant technology was performed in 3 cases and stent assistant technology in another 3 cases. RESULTS: All the 30 paraclinoid aneurysms were treated. One patient with bilateral paraclinoid aneurysms became blind after bilateral microsurgical procedures and another patient was unexceptedly dead 10 d after operation. Vasospasm resulting with cerebral infarction occurred in one case who received endovascular embolism, while two patients suffered from hydrocephalus. Ten cases of microsurgical group and 9 cases of interventional group were followed up with digital subtraction angiography, which disclosed that 9 cases of microsurgical group were clipped completely, while 7 aneurysms of interventional group were completely embolised. One aneurysm recurred and enlarged 12 months after stent assistant embolism, and after STA-MCA bypass and bilateral anterior cerebral artery anastomy and aneurysm insulation, the patient recovered well. When the patients were discharged, their Glasgow outcome scales showed that 18 cases were with 5, 8 with 4, 1 with 3 and 1 with 0. CONCLUSION: According to the classification, and with appropriate treatment, the patients with paraclinoid aneurysms will get good outcomes both with microsurgical clipping and with endovascular embolization. PMID- 26284410 TI - [Influence of dexamethasone on the incidence of postoperative nausea and vomiting in breast cancer patients with neoadjuvant chemotherapy]. AB - OBJECTIVE: To evaluate the influence of dexamethasone on the incidence of postoperative nausea and vomiting (PONV) in patients undergoing modified radical mastectomy with neoadjuvant chemotherapy. METHODS: In a prospective trial, 280 female (18-60 years) breast cancer patients undergoing modified radical mastectomy with neoadjuvent chemotherapy were randomized to two groups: one with dexamethasone (Group D) and one without dexamethasone (Group C, n=140). In each group, anesthesia was maintained with volatile anesthesia or total intravenous anesthesia (TIVA): TIVA (propofol) without dexamethasone (Subgroup CP); volatile anesthesia (sevoflurane) without dexamethasone (Subgroup CS); TIVA with 10 mg dexamethasone intravenously before anesthetic induction (Subgroup DP); volatile anesthesia with 10 mg dexamethasone intravenously before anesthetic induction (Subgroup DS). A standard general anesthetic technique was used. All the patients received 8 mg of ondansetron intravenously 30 minutes before the end of surgical procedures. The incidence of PONV during the 24-hour postoperative period was recorded. A Logistic regression analysis was conducted to examine relevant factors for PONV. The tested factors were: age, body mass index (BMI), duration of surgery, postoperative pain, history of motion sickness/PONV, with or without dexamethasone and anesthetic regimen. RESULTS: There was a significant lower incidence of PONV in the patients who received dexamethasone than in those who received placebo during the 24-hour postoperative period (11.4% vs. 20.7%, P=0.034). In the early postoperative period (0-2 h) dexamethasone reduced the incidence of PONV ( 1.4%vs.6.4%, P=0.031), but in the late postoperative period (2-24 h) the difference of the incidence was insignificantly (10.7% vs. 17.9%, P=0.088). No differences were found between TIVA and volatile anesthesia in the 24-hour postoperative period. Dexamethasone was effective to prevent PONV(OR=0.447, P=0.030), and history of PONV or motion sickness was the risk factor of PONV (OR=15.730, P<0.001). CONCLUSION: Dexamethasone prevents PONV effectively in patients undergoing modified radical mastectomy with neoadjuvant chemotherapy, and TIVA cannot decrease the incidence of PONV in the 24-hour postoperative period in those patients. PMID- 26284411 TI - [Effect of 1,4-naphthoquinone aged black carbon on reactive oxygen species and DNA strand breaks in human bronchial epithelial cells]. AB - OBJECTIVE: To study the effect of 1,4-naphthoquinone aged black carbon (BC/1,4 NQ) on reactive oxygen species and DNA strand breaks in human bronchial epithelial cells (16HBE). METHODS: In the study, 16HBE cells were exposed to BC/1,4-NQ, BC and 1,4-NQ at the concentrations of BC/1,4-NQ (10.0/0.2, 20.0/0.4, 40.0/0.8, 80.0/1.6, 160.0/3.2 mg/L), BC (10.0, 20.0, 40.0, 80.0, 160.0 mg/L), 1,4 NQ (0.2, 0.4, 0.8, 1.6, 3.2 mg/L) for 24, 48, and 72 h, respectively. Cytotoxicity was detected by cell count kit 8 (CCK-8) at the end point. Then the 16HBE cells were exposed to BC/1,4-NQ (20.0/0.4, 40.0/0.8, 80.0/1.6 mg/L), BC (20.0, 40.0, 80.0 mg/L), 1,4-NQ (0.4, 0.8, 1.6 mg/L) for 24 h. The reactive oxygen species (ROS) generation was determined via flow cytometry with DCFH-DA probe. Single cell gel electrophoresis (SCGE) assay was performed to evaluate genotoxicity by Olive tail moment (OTM) value. RESULTS: Except for the concentration of 10.0/0.2 mg/L within the exposure time 24 h, the cell viabilities of BC/1,4-NQ were significantly lower than the control (P<0.05) within the exposure time 24-72 h, showing a dose-dependent cytotoxicity. Especially, BC/1,4-NQ showed greater cytotoxicity than BC single exposure, lower than 1,4-NQ at the concentration of BC/1,4-NQ>=80.0/1.6 mg/L. BC/1,4-NQ also showed greater ROS generation and OTM value than the control within the exposure time 24 h at each concentration (P<0.05). Especially, the ROS generation and OTM value of BC/1,4-NQ were greater than BC single exposure, lower than 1,4-NQ at the concentration of 80.0/1.6 mg/L (P<0.05). CONCLUSION: BC/1,4-NQ can induce intracellular ROS generation, cytotoxicity and genotoxicity in 16HBE cells. And at high concentration, the intracellular ROS level, cytotoxicity and genotoxicity induced by BC/1,4-NQ were greater than those by BC single exposure, but lower than those by 1,4-NQ. PMID- 26284412 TI - [Relationship between vitamin D receptor gene polymorphisms and chronic periodontitis]. AB - OBJECTIVE: To investigate the relationship between vitamin D receptor (VDR) gene polymorphisms and chronic periodontitis(CP). METHODS: Buccal swabs from 105 patients with mild/mode-rate CP and 85 severe CP were collected, DNA was extracted from these buccal swabs using the TIANamp Swab DNA Kit [TIANGEN Biotech (Beijing) CO.Ltd]. The VDR rs1544410 and rs731236 were genotyped by the Sequenom MassARRAY system (Shanghai Benegene Biotechnology Co. Ltd), which was based on MALDI-TOF (matrix-assisted laser desorption ionization time-of-flight) technology. The distribution of the genotypes and allele frequencies were analyzed. RESULTS: The frequencies of the rs1544410 A allele and AA+AG genotype were significantly higher in severe CP than in mild/moderate CP of all the patients and the female patients respectively (all the patients: P=0.006, 0.007; the female patients: P=0.001, 0.001). The frequencies of the rs731236 C allele and CC+CT genotype were significantly higher in severe CP than in mild/moderate CP of all the patients and the female patients respectively (all the patients: P=0.003, 0.004; the female patients: P<0.001, <0.001). CONCLUSION: Gene polymorphisms of VDR rs731236 and rs1544410 may be associated with severe CP in Chinese Han population. PMID- 26284413 TI - [Three-dimensional evaluation of condylar morphology remodeling after orthognathic surgery in mandibular retrognathism by cone-beam computed tomography]. AB - OBJECTIVE: To evaluate the effect of orthognathic surgery on condylar morphology changes by comparing three-dimension surface reconstructions of condyles using cone-beam computed tomography (CBCT) data. METHODS: In the study, 18 patients with mandible retrognathism deformities were included and CBCT data of 36 temporomandibular joints were collected before surgery and 12 months after surgery. Condyles were reconstructed and superimposed pre- and post-operatively to compare the changes of condylar surfaces. One-sample t test and chi2 test were performed for the analysis of three-dimension metric measurement and condylar head remodeling signs. P<0.05 was considered significant. RESULTS: The root-mean square (RMS) of condylar surface changes before and after the surgery was (0.37+/ 0.11) mm, which was significant statistically (P<0.05). The distribution of condylar remodeling signs showed significant difference (P<0.05). Bone resorption occurred predominantly in the posterior area of condylar head and bone formation occurred mainly in the anterior area. CONCLUSION: Three-dimension superimposition method based on CBCT data showed that condylar morphology had undergone remodeling after mandibular advancement. PMID- 26284414 TI - [Three-dimensional measurement and facial symmetry analysis for the craniofacial structure of people in North China with normal occlusion]. AB - OBJECTIVE: To investigate the internal regularities and symmetry of craniofacial structures from adults with normal occlusion in North China. METHODS: The study consisted of 60 volunteers who were examined with spiral 3D computed tomography (CT). The axial images of craniofacial structure were reconstructed into 3D models and analyzed by using Proplan 1.2 software to measure the internal regularities and symmetry of craniofacial structures. RESULTS: All the linear measurement's value of the males were bigger than those of the females (P<0.05). There were no significant differences in the ratio measurements between the males and the females(P>0.05). Facial asymmetry was less than 10% in all the images. CONCLUSION: CT is an effective method for three-dimensional analyses of craniofacial structure and symmetry. There are certain and harmonious regularities in normal 3D craniofacial structures. The 3D craniofacial structure database of people with normal occlusion can provide standards and references for diagnosis and treatment planning of craniofacial deformities. PMID- 26284415 TI - [Multiple primary neoplasms with renal neurilemmoma: a case report and literature review]. AB - Multiple primary neoplasms are not common, those containing renal neurilemoma are even more rare. Our study involves the diagnosis and treatment of a female patient with multiple primary neoplasms with renal neurilemoma. She was previously diagnosed with left ovarian dermoid cyst, right posterior mediastinal neurilemmoma, left forearm neurilemmoma, and papillary thyroid carcinoma, underwent operation treatment. Physical examination reveals a left renal mass with a left adrenal tumor a month before, and underwent retroperitoneal laparoscopic left adrenal nodule resection and left partial nephrectomy. Operation was successful, without conversions to open. Artery occlusion time was 18 min, and blood loss was 20 mL. Post operation pathologic result shows a left renal cellular leiomyoma neurilemmoma with focal cystic change, and tumor diameter was about 3 cm. Immunohistochemistry reports S-100 (+), Ki-67 (15%+), and short-term follow-up without recurrence. In our case of study, even though the tumors were heterochronism, they were both treated with surgical resection. Renal neurilemoma is benign. Laparoscopic partial nephrectomy is not only minimally invasive, fast in recovery, but most importantly preserves renal tissue to the largest extent. It can prevent preoperative pathological uncertainty, which often undergoes radical nephrectomy. PMID- 26284416 TI - [Progress in diagnosis and treatment of adrenal metastases tumor]. AB - The adrenal gland is a common site of metastases, only second to pulmonary, liver and bone. The prevalence of adrenal metastases in patients with a history of cancer is between 10%-25%.The most common sites of origin are cancers of the lung, kidney, breast, gastrointestinal tract, and skin (melanoma).The mainstays of adrenal metastases diagnosis are computerized tomogramphy (CT), magnetic resonance imaging (MRI), and positron emission tomogramphy (PET). All patients should undergo complete hormonal evaluation to rule out functional adrenal tumors. Adrenal biopsy should be reserved for cases in which the results of non invasive techniques are equivocal. In patients with isolated adrenal metastases, adrenalectomy is recommended, because of improved overall survival. For the patient with unresectable adrenal metastases tumor, radiotherapy and ablative therapy are feasible and useful methods for controlling adrenal metastases and offer patients opportunities for improved survival. PMID- 26284418 TI - Ten Years of Abstinence in Former Opiate Addicts: Medication-Free Non-Patients Compared to Methadone Maintenance Patients. AB - Fifty-five former opioid addicts who have been methadone maintained patients for 10 or more years and whose urine has tested negative for drugs for 2 or more years were compared to 99 former opioid addicts who have been medication-free for 10 or more years. Groups were comparable in age and education, but the medication free subjects were younger when having started opioids with more severe addiction scores. Methadone maintained patients presented with a higher proportion of psychiatric comorbidity and chronic pain. Their scores of perceived sleep quality and cognitive state were poorer than the medication-free individuals. Possible explanations of the differences are discussed in this article. PMID- 26284420 TI - Tolerance to Dose Escalation in Minibeam Radiation Therapy Applied to Normal Rat Brain: Long-Term Clinical, Radiological and Histopathological Analysis. AB - The major limitation to reaching a curative radiation dose in radioresistant tumors such as malignant gliomas is the high sensitivity to radiation and subsequent damage of the surrounding normal tissues. Novel dose delivery methods such as minibeam radiation therapy (MBRT) may help to overcome this limitation. MBRT utilizes a combination of spatial fractionation of the dose and submillimetric (600 MUm) field sizes with an array ("comb") of parallel thin beams ("teeth"). The dose profiles in MBRT consist of peaks and valleys. In contrast, the seamless irradiations of the several squared centimeter field sizes employed in standard radiotherapy result in homogeneous dose distributions (and consequently, flat dose profiles). The innovative dose delivery methods employed in MBRT, unlike standard radiation therapy, have demonstrated remarkable normal tissue sparing. In this pilot work, we investigated the tolerance of the rat brain after whole-brain MBRT irradiation. A dose escalation was used to study the tissue response as a function of dose, so that a threshold could be established: doses as high as 100 Gy in one fraction were still well tolerated by the rat brain. This finding suggests that MBRT may be used to deliver higher and potentially curative radiation doses in clinical practice. PMID- 26284419 TI - Determination and surveillance of hydrocortisone and progesterone in livestock products by liquid chromatography-tandem mass spectrometry. AB - A simple analytical method for the determination of hydrocortisone and progesterone in bovine, swine, and chicken muscle and eggs was developed. Hydrocortisone and progesterone were extracted with acetonitrile and subsequently cleaned-up using an Oasis HLB mini-cartridge. The method was validated in accordance with Japanese guidelines and exhibited trueness from 86.6% to 104.3% and precision (relative standard deviations (RSDs) of repeatability and within reproducibility were under 8.7% and 11.7%, respectively). The method was applied to 103 bovine muscle, 137 swine muscle, 69 chicken muscle and 52 egg samples that were commercially available in Tokyo, Japan. The hydrocortisone concentration was 0.9-41.2 ug kg(-1) in all bovine muscle samples, with an average of 7.7 ug kg(-1) and a median of 6.2 ug kg(-1). The progesterone concentration in 50 samples exceeded the limit of quantification (LOQ) and reached a maximum of 95.4 ug kg( 1). Hydrocortisone was also detected in all swine muscle samples at concentrations of 2.0-56.0 ug kg(-1). Its average and median concentrations amounted to 13.1 and 11.3 ug kg(-1), respectively. Twenty-three samples contained progesterone levels surpassing the LOQ, with a maximum concentration of 107.0 ug kg(-1). No chicken muscle samples contained any of the analytes. The progesterone concentration was 15.5-200.0 ug kg(-1) in all egg samples, with an average of 95.4 ug kg(-1) and a median of 90.5 ug kg(-1). PMID- 26284421 TI - Comparison of the Effectiveness of Exposure to Low-LET Helium Particles ((4)He) and Gamma Rays ((137)Cs) on the Disruption of Cognitive Performance. AB - In this study, the effects of radiation exposure on cognitive performance were evaluated. Rats were exposed to either helium ((4)He) particles (1,000 MeV/n; 0.1 10 cGy; head only) or cesium (137)Cs gamma rays (50-400 cGy; whole body), after which their cognitive performance was evaluated. The results indicated that exposure to doses of (4)He particles as low as 0.1 cGy disrupted performance in a variety of cognitive tasks, including plus-maze performance (baseline anxiety), novel location recognition (spatial performance) and operant responding on an ascending fixed-ratio reinforcement schedule (motivation and responsiveness to changes in environmental contingencies) but not on novel object recognition performance (learning and memory). In contrast, after exposure to (137)Cs gamma rays only plus-maze performance was affected. There were no significant effects on any other task. Because exposure to both types of radiation produce oxidative stress, these results indicate that radiation-produced oxidative stress may be a necessary condition for the radiation-induced disruption of cognitive performance, but it is not a sufficient condition. PMID- 26284422 TI - Co-culturing with High-Charge and Energy Particle Irradiated Cells Increases Mutagenic Joining of Enzymatically Induced DNA Double-Strand Breaks in Nonirradiated Cells. AB - Cell populations that have been exposed to high-charge and energy (HZE) particle radiation, and then challenged by expression of a rare-cutting nuclease, show an increased frequency of deletions and translocations originating at the enzyme cut sites. Here, we examine whether this effect also occurs in nonirradiated cells that have been co-cultured with irradiated cells. Human cells were irradiated with 0.3-1.0 Gy of either 600 MeV/u (56)Fe or 1,000 MeV/u (48)Ti ions or with 0.3 3.0 Gy of 320 kV X rays. These were co-cultured with I-SceI-expressing reporter cells at intervals up to 21 days postirradiation. Co-culture with HZE-irradiated cells led to an increase in the frequency of I-SceI-stimulated translocations and deletions in the nonirradiated cells. The effect size was similar to that seen previously in directly irradiated populations (maximum effect in bystander cells of 1.7- to 4-fold depending on ion and end point). The effect was not observed when X-ray-irradiated cells were co-cultured with nonirradiated cells, but was correlated with an increase in gamma-H2AX foci-positive cells in the nonirradiated population, suggesting the presence of genomic stress. Transcriptional profiling of a directly irradiated cell population showed that many genes for cytokines and other secretory proteins were persistently upregulated, but their induction was not well correlated with functional effects on repair in co-cultured cells, suggesting that this transcriptional response alone is not sufficient to evoke the effect. The finding that HZE-irradiated cells influence the DNA double-strand break repair fidelity in their nonirradiated neighbors has implications for risk in the space radiation environment. PMID- 26284423 TI - Radioprotectors and Radiomitigators for Improving Radiation Therapy: The Small Business Innovation Research (SBIR) Gateway for Accelerating Clinical Translation. AB - Although radiation therapy is an important cancer treatment modality, patients may experience adverse effects. The use of a radiation-effect modulator may help improve the outcome and health-related quality of life (HRQOL) of patients undergoing radiation therapy either by enhancing tumor cell killing or by protecting normal tissues. Historically, the successful translation of radiation effect modulators to the clinic has been hindered due to the lack of focused collaboration between academia, pharmaceutical companies and the clinic, along with limited availability of support for such ventures. The U.S. Government has been developing medical countermeasures against accidental and intentional radiation exposures to mitigate the risk and/or severity of acute radiation syndrome (ARS) and the delayed effects of acute radiation exposures (DEARE), and there is now a drug development pipeline established. Some of these medical countermeasures could potentially be repurposed for improving the outcome of radiation therapy and HRQOL of cancer patients. With the objective of developing radiation-effect modulators to improve radiotherapy, the Small Business Innovation Research (SBIR) Development Center at the National Cancer Institute (NCI), supported by the Radiation Research Program (RRP), provided funding to companies from 2011 to 2014 through the SBIR contracts mechanism. Although radiation-effect modulators collectively refer to radioprotectors, radiomitigators and radiosensitizers, the focus of this article is on radioprotection and mitigation of radiation injury. This specific SBIR contract opportunity strengthened existing partnerships and facilitated new collaborations between academia and industry. In this commentary, we assess the impact of this funding opportunity, outline the review process, highlight the organ/site specific disease needs in the clinic for the development of radiation-effect modulators, provide a general understanding of a framework for gathering preclinical and clinical evidence to obtain regulatory approval and provide a basis for broader venture capital needs and support from pharmaceutical companies to fully capitalize on the advances made thus far in this field. PMID- 26284424 TI - The molecular mode of action and species specificity of canakinumab, a human monoclonal antibody neutralizing IL-1beta. AB - Interleukin-1beta (IL-1beta) plays a key role in autoinflammatory diseases, such as systemic juvenile idiopathic arthritis (sJIA) or cryopyrin-associated periodic syndrome (CAPS). Canakinumab, a human monoclonal anti-IL-1beta antibody, was recently approved for human use under the brand name Ilaris(r). Canakinumab does not cross-react with IL-1beta from mouse, rat, rabbit, or macaques. The crystal structure of the canakinumab Fab bound to human IL-1beta was determined in an attempt to rationalize the species specificity. The X-ray analysis reveals a complex surface epitope with an intricate network of well-ordered water molecules at the antibody-antigen interface. The canakinumab paratope is largely pre organized, as demonstrated by the structure determination of the free Fab. Glu 64 of human IL-1beta is a pivotal epitope residue explaining the exquisite species specificity of canakinumab. We identified marmoset as the only non-human primate species that carries Glu 64 in its IL-1beta and demonstrates full cross reactivity of canakinumab, thereby enabling toxicological studies in this species. As demonstrated by the X-ray structure of the complex with IL-1beta, canakinumab binds IL-1beta on the opposite side with respect to the IL-1RAcP binding site, and in an approximately orthogonal orientation with respect to IL 1RI. However, the antibody and IL-1RI binding sites slightly overlap and the VH region of canakinumab would sterically interfere with the D1 domain of IL-1RI, as shown by a structural overlay with the IL-1beta:IL-1RI complex. Therefore, direct competition with IL-1RI for IL-1beta binding is the molecular mechanism of neutralization by canakinumab, which is also confirmed by competition assays with recombinant IL-1RI and IL-1RII. PMID- 26284426 TI - A Neutralizing Prolactin Receptor Antibody Whose In Vivo Application Mimics the Phenotype of Female Prolactin Receptor-Deficient Mice. AB - The prolactin receptor (PRLR) has been implicated in a variety of physiological processes (lactation, reproduction) and diseases (breast cancer, autoimmune diseases). Prolactin synthesis in the pituitary and extrapituitary sites is regulated by different promoters. Dopamine receptor agonists such as bromocriptine can only interfere with pituitary prolactin synthesis and thus do not induce a complete blockade of PRLR signaling. Here we describe the identification of a human monoclonal antibody 005-C04 that blocks PRLR-mediated signaling at nanomolar concentrations in vitro. In contrast to a negative control antibody, the neutralizing PRLR antibody 005-C04 inhibits signal transducer and activator of transcription 5 phosphorylation in T47D cells and proliferation of BaF3 cells stably expressing murine or human PRLRs in a dose-dependent manner. In vivo application of this new function-blocking PRLR antibody reflects the phenotype of PRLR-deficient mice. After antibody administration female mice become infertile in a reversible manner. In lactating dams, the antibody induces mammary gland involution and negatively interferes with lactation capacity as evidenced by reduced milk protein expression in mammary glands and impaired litter weight gain. Antibody-mediated blockade of the PRLR in vivo stimulates hair regrowth in female mice. Compared with peptide-derived PRLR antagonists, the PRLR antibody 005-C04 exhibits several advantages such as higher potency, noncompetitive inhibition of PRLR signaling, and a longer half-life, which allows its use as a tool compound also in long-term in vivo studies. Therefore, we suggest that this antibody will help to further our understanding of the role of auto- and paracrine PRLR signaling in health and disease. PMID- 26284425 TI - Type 2 Iodothyronine Deiodinase Activity Is Required for Rapid Stimulation of PI3K by Thyroxine in Human Umbilical Vein Endothelial Cells. AB - Thyroid hormones (THs) exert a number of physiological effects on the cardiovascular system. Some of the nongenomic actions of T3 are achieved by cross coupling the TH receptor (TR) with the phosphatidylinositol 3-kinase (PI3K)/protein kinase Akt (Akt) pathway. We observed that both T3 and T4 rapidly stimulated Akt phosphorylation and Ras-related C3 botulinum toxin substrate 1 (Rac1) activation, which resulted in cell migration, in a PI3K-dependent manner in human umbilical vein endothelial cells (HUVECs). We identified the expression of type 2 iodothyronine deiodinase (D2), which converts T4 to T3, and TRalpha1 in HUVECs. D2 activity was significantly stimulated by (Bu)2cAMP in HUVECs. The blockade of D2 activity through transfection of small interfering RNA (siRNA) specific to D2 as well as by addition of iopanoic acid, a potent D2 inhibitor, abolished Akt phosphorylation, Rac activation, and cell migration induced by T4 but not by T3. The inhibition of TRalpha1 expression by the transfection of siRNA for TRalpha1 canceled Akt phosphorylation, Rac activation, and cell migration induced by T3 and T4. These findings suggest that conversion of T4 to T3 by D2 is required for TRalpha1/PI3K-mediated nongenomic actions of T4 in HUVECs, including stimulation of Akt phosphorylation and Rac activation, which result in cell migration. PMID- 26284427 TI - Oral Nucleotides Only Minimally Improve 5-Fluorouracil-Induced Mucositis in Rats. AB - Chemotherapy-induced mucositis is characterized by inflammation and ulceration of the intestinal mucosa, compromising intestinal function. Exogenous nucleotides have been reported to repair the mucosa. The nucleotide preparation, Nucleoforce F0328 (Nucleoforce), was investigated for its potential to ameliorate intestinal mucositis in rats. Female Dark Agouti rats (n = 8/group) were gavaged once daily with Nucleoforce (175 mg/kg) or water from Days 0 to 8 and injected (i.p.) with 5 fluorouracil (5-FU; 150 mg/kg) or saline on Day 5. Histological parameters (disease severity, crypt depth, and villus height measurements) and myeloperoxidase activity were quantified. P < 0.05 was considered significant. Jejunal and ileal histological disease severity scores were significantly increased by 5-FU, compared to normal controls (P < 0.05). Nucleoforce treatment in 5-FU-injected rats significantly reduced jejunal and ileal disease severity compared to 5-FU controls (P < 0.05). In 5-FU-injected rats, jejunal and ileal villus heights and crypt depths were significantly decreased compared to 5-FU controls, with no additional Nucleoforce effect (P > 0.05). Intestinal myeloperoxidase activity was significantly elevated by 5-FU (8.8-fold), compared to normal controls (P < 0.05), which was not normalized by Nucleoforce treatment (P > 0.05). Nucleoforce only partially improved parameters associated with experimentally-induced mucositis. Future studies could investigate increased concentrations, more frequent administration, or protective microencapsulation delivery methods, to increase bioavailability. PMID- 26284428 TI - Additive effect of Lygodium venustum SW. in association with gentamicin. AB - The aim of this work was to evaluate the interactions between gentamicin and the ethanol extract of the fern Lygodium venustum SW (EELV). The ethanol extract of L. venustum was obtained, the phytocompounds were identified and the EELV was assayed by the checkerboard method with gentamicin against two bacterial strains multiresistant to antibiotics. The antibiotic activity of gentamicin, when associated with the extract, was enhanced in an additive manner against both strains. The results indicated that L. venustum can be a source of secondary metabolites to be used in association with antibiotics as aminoglycosides in the antibiotic chemotherapy against resistant bacteria. PMID- 26284429 TI - Medical interventions for high-grade vulval intraepithelial neoplasia. AB - BACKGROUND: This is an updated version of a review first published in theCochrane Database of Systematic Reviews, Issue 4, in 2011. Vulval intraepithelial neoplasia (VIN) is a pre-cancerous condition of the vulval skin and its incidence is increasing in women under 50 years. High-grade VIN (also called usual-type VIN (uVIN) or VIN 2/3 or high-grade vulval intraepithelial lesion) is associated with human papilloma virus (HPV) infection and may progress to vulval cancer, therefore is usually actively managed. There is no consensus on the optimal management of high-grade VIN; and the high morbidity and relapse rates associated with surgical interventions make less invasive interventions highly desirable. OBJECTIVES: To evaluate the effectiveness and safety of medical (non-surgical) interventions for high-grade VIN. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 3), MEDLINE and EMBASE (up to 30 March 2015). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) that assessed non-surgical interventions in women diagnosed with high grade VIN. DATA COLLECTION AND ANALYSIS: We used Cochrane methodology with two review authors independently abstracting data and assessing risk of bias. Where possible, we synthesised data in meta-analyses using random effects methods. MAIN RESULTS: Five trials involving 297 women with high-grade VIN (defined by trial investigators as VIN 2/3 or VIN 3 or 'high-grade' lesions) met our inclusion criteria: three trials assessed the effectiveness of topical imiquimod versus placebo; one assessed topical cidofovir versus topical imiquimod; and one assessed low- versus high-dose indole-3-carbinol in similar types of participants. Three trials were at a moderate to low risk of bias, two were at a potentially high risk of bias.Meta-analysis of the three trials comparing topical imiquimod 5% cream to placebo found that women in the active treatment group were more likely to show an overall response (complete and partial response) to treatment at five to six months compared with the placebo group (Risk Ratio (RR) 11.95, 95% confidence interval (CI) 3.21 to 44.51; participants = 104; studies = 3; I(2) = 0%; high-quality evidence). A complete response at five to six months occurred in 36/62 (58%) and 0/42 (0%) participants in the active and placebo groups, respectively (RR 14.40, 95% CI 2.97 to 69.80; participants = 104; studies = 3; I(2) = 0%). A single trial reported 12-month follow-up, which revealed a sustained effect in overall response in favour of the active treatment arm at 12 months (RR 9.10, 95% CI 2.38 to 34.77; moderate-quality evidence), with 9/24 (38%) and 0/23 (0%) complete responses recorded in the active and placebo groups respectively. Progression to vulval cancer was also documented in this trial (one versus two participants in the active and placebo groups, respectively) and we assessed this evidence as low-quality. Only one trial reported adverse events, including erythema, erosion, pain and pruritis at the site of the lesion, which were more common in the imiquimod group. Dose reductions occurred more frequently in the active treatment group compared with the placebo group (19/47 versus 1/36 participants; RR 7.77, 95% CI 1.61 to 37.36; participants = 83; studies = 2; I(2) = 0%; high-quality evidence). Only one trial reported quality of life (QoL) and there were no significant differences between the imiquimod and placebo groups.For the imiquimod versus cidofovir trial, 180 women contributed data. The overall response at six months was similar for the imiquimod and cidofovir treatment groups with 52/91 (57%) versus 55/89 (62%) participants responding, respectively (RR 0.92, 95% CI 0.73 to 1.18). A complete response occurred in 41 women in each group (45% and 46%, respectively; RR 1.00, 95% CI 0.73 to 1.37). Although not statistically different, total adverse events were slightly more common in the imiquimod group of this trial with slightly more discontinuations occurring in this group. Longer term response data from this trial are expected.The small trial comparing two doses of indole-3-carbinol contributed limited data. We identified five ongoing randomised trials of various interventions for VIN. AUTHORS' CONCLUSIONS: Topical imiquimod appears to be a safe and effective treatment for high-grade VIN (uVIN), even though local side effects may necessitate dose reductions. However, longer term follow-up data are needed to corroborate the limited evidence that response to treatment is sustained, and to assess any effect on progression to vulval cancer. Available evidence suggests that topical cidofovir may be a good alternative to imiquimod; however, more evidence is needed, particularly regarding the relative effectiveness on longer term response and progression. We await the longer-term response data and the results of the five ongoing trials. PMID- 26284430 TI - Matching between oral inward-outward movements of object names and oral movements associated with denoted objects. AB - In eight experiments, we explored matching effects between oral approach avoidance movements triggered by word articulation and meaning of the objects the words denoted. Participants (total N = 1264) rated their liking for words that featured consonantal muscle stricture spots either wandering inwards (e.g., BODIKA, resembling ingestion movements) or outwards (e.g., KODIBA, resembling expectoration movements). These words were labelled as names for various objects. For objects the use of which entails ingestive oral actions (lemonade and mouthwash) inward words were preferred over outward words. For objects that trigger expectorative oral actions (toxical chemical, pill, and bubble gum) this preference was attenuated or even reversed (outward words were liked more than inward). Valence of the denoted object did not play a role in these modulations. Thus, the sagittal direction of mouth movements during silent reading meaningfully interacted with direction of oral actions associated with the denoted objects. PMID- 26284431 TI - Correction to online hydrogen-isotope measurements of organic samples using elemental chromium: an extension for high-temperature elemental-analyzer techniques. PMID- 26284432 TI - Large Heterogeneity in Mean Durations of Labor Analgesia Among Hospitals Reporting to the American Society of Anesthesiologists' Anesthesia Quality Institute. AB - BACKGROUND: Variability in the mean durations of labor analgesia for vaginal delivery among hospitals is unknown. Such differences in means among hospitals would influence appropriate equitable fee-for-service payment to US anesthesia groups. Equitable payment is the foundational principle of relative value unit payment, which, for anesthesia in the United States, means use of the American Society of Anesthesiologist's Relative Value Guide. METHODS: We analyzed data from the American Society of Anesthesiologists' Anesthesia Quality Institute to test whether there are large differences in mean durations of labor analgesia for vaginal delivery among US hospitals. We choose the statistical methodology for that analysis using detailed data from 2 individual hospitals. Analyses of the means were performed for the 172 hospitals reporting a total of at least 200 durations; having no greater than 5.0% of durations 1.0 hour or less; and at least 5 four-week periods each having a mean of at least one epidural every couple of days. The 172 hospitals provided for n = 5671 combinations of hospital and 4-week period and 551,707 labor epidurals, with an overall mean duration of 6.12 hours (SE, 0.001 hour). RESULTS: 55.2% of the 172 hospitals had mean durations of labor analgesia for vaginal delivery that each differed (P < 0.001) from the overall mean. Among those 55.2% were the 9.9% of hospitals with means <=5.12 hours. Those mean durations on the low end ranged from 2.68 (SE, 0.17) to 5.10 (SE, 0.07) hours. Also, among the 55.2% were the 12.2% of hospitals with means >=7.12 hours. Those mean durations at the high end ranged from 7.13 (SE, 0.08) to 12.03 (SE, 0.23) hours. The heterogeneity in the mean durations among hospitals would have been greater had the inclusion criteria not been applied. CONCLUSIONS: Our results show that the number of labor epidurals alone is not a valid measure to quantify obstetrical anesthesia productivity. In addition, payment to US anesthesia groups for labor analgesia based solely on the number of labor epidurals initiated is not equitable. Previous work showed lack of validity and equality of payment based on face-to-face time with the patient (i.e., like a surgical anesthetic). The use of base and time units, with one time unit per hour, is a suitable payment system. PMID- 26284433 TI - Insights into N-doping in single-walled carbon nanotubes for enhanced activation of superoxides: a mechanistic study. AB - Emerging characteristics upon nitrogen-doping were differentiated in the activation of superoxides over single-walled carbon nanotubes. Both experimental and theoretical studies revealed that enhanced peroxymonosulfate (PMS) activation is ascribed to a nonradical process while persulfate (PS) activation is accelerated via directly oxidizing water, yet hydrogen peroxide (H2O2) activation is inert to N-doping. This study details the first insights into versatile N doping in carbocatalysis for organic oxidation in sustainable remediation. PMID- 26284434 TI - Copper-catalysed azide-alkyne cycloadditions (CuAAC): an update. AB - The reactions of organic azides and alkynes catalysed by copper species represent the prototypical examples of click chemistry. The so-called CuAAC reaction (copper-catalysed azide-alkyne cycloaddition), discovered in 2002, has been expanded since then to become an excellent tool in organic synthesis. In this contribution the recent results described in the literature since 2010 are reviewed, classified according to the nature of the catalyst precursor: copper(I) or copper(II) salts or complexes, metallic or nano-particulated copper and several solid-supported copper systems. PMID- 26284435 TI - High-Pitch Low-Dose Whole-Body Computed Tomography for the Assessment of Ventriculoperitoneal Shunts in a Pediatric Patient Model: An Experimental Ex Vivo Study in Rabbits. AB - OBJECTIVE: The aim of this study was to assess the diagnostic value of whole-body low-dose (LD) computed tomography (CT) for the detection of ventriculoperitoneal (VP) shunt complications in pediatric patients compared with radiographic shunt series (SS) in an ex vivo rabbit animal model. METHODS: In the first step, 2 optimized LD-CT imaging protocols, with high pitch (pitch, 3.2), low tube voltages (70 kVp and 80 kVp), and using both filtered back projection and iterative reconstruction, were assessed on a 16-cm solid polymethylmethacrylate phantom regarding signal-to-noise ratio and radiation dose. Taking both radiation dose and signal-to-noise ratio into account, the LD-CT protocol (80 kVp; 4 mA; pitch, 3.2) was identified as most appropriate and therefore applied in this study.After identification of appropriate LD-CT protocol, 12 VP shunts were implanted in 6 rabbit cadavers (mean weight, 5.1 kg). Twenty-four mechanical complications (extracranial and extraperitoneal malpositioning, breakages, and disconnections) were induced in half of the VP shunts. Low-dose CT and conventional SS were acquired in standard fashion. Dose-area products (DAPs) for SS and LD-CT were collected; effective radiation doses for both SS and LD-CT were estimated using CT-Expo (v. 2.3.1.) and age-specific effective dose (ED) estimates. Qualitative scoring of diagnostic confidence on a 5-point Likert scale (1, very low diagnostic confidence; 5, excellent diagnostic confidence) and blinded readings of both SS and LD-CTs were performed. RESULTS: Among the 24 VP shunt complications, LD-CT yielded excellent sensitivity and specificity for the detection of VP shunt complications (sensitivity, 0.98; specificity, 1; 95% confidence interval, 0.92-1) with excellent interobserver agreement (kappa = 0.90). Shunt series yielded good sensitivity and specificity (sensitivity, 0.75; specificity, 1; 95% confidence interval, 0.58-0.92) with moderate interobserver agreement (kappa = 0.56). No false-positive findings were registered. Compared with SS, LD-CT yielded significantly lower ED and DAPs (ED, 0.039 vs 0.062 mSv; DAP, 20.5 vs 26.3; P < 0.05). CONCLUSIONS: In this experimental ex vivo pediatric patient model, LD-CT yields excellent sensitivity for the detection of VP shunt complications at higher diagnostic confidence and lower radiation exposure compared with SS. PMID- 26284436 TI - Magnetic Resonance Imaging of the Temporomandibular Joint at 7.0 T Using High Permittivity Dielectric Pads: A Feasibility Study. AB - OBJECTIVES: The aims of this study were to show feasibility and to quantitatively and qualitatively evaluate the use of high-permittivity dielectric pads for imaging the temporomandibular joint (TMJ) at 7.0 T. MATERIALS AND METHODS: This study is an institutional review board-approved study with written informed consent. Ten asymptomatic volunteers (20 TMJs) were magnetic resonance imaged using a 32-channel head coil at 7.0 T (Achieva; Philips Healthcare, the Netherlands) with and without high-permittivity dielectric pads consisting of barium titanate in deuterated suspension. Imaging protocol consisted of an oblique sagittal proton density-weighted turbo-spin echo sequence. For quantitative evaluation, B1 maps and voxelwise signal-to-noise ratio (SNR) maps were calculated. For qualitative evaluation, 2 readers assessed the visibility of anatomical structures of the TMJ and overall image quality on a 5-point Likert scale from 1 (excellent visibility) to 5 (not visible) in consensus. Quantitative and qualitative measurements were compared between images acquired with and without pads. RESULTS: Imaging the TMJ using dielectric pads was feasible in all volunteers. The quantitative analysis showed locally higher B1+ and higher SNR in the area covering the TMJ for the scans performed with dielectric pads compared with those without pads (SNR: mean [SD] pads, 12.38 [3.18]; mean [SD] no pads, 6.60 [0.72]). The qualitative analysis showed significantly better visibility and delineation of clinically relevant anatomical structures of the TMJ, including temporomandibular disc, bilaminar zone, mandibular fossa, mandibular condyle, and pterygoid muscle. In addition, observers judged overall image quality as better for images taken with pads compared with those taken without pads (mean [SD] pads, 1.40 [0.50]; mean [SD] no pads, 4.25 [0.78]). CONCLUSIONS: The application of high-permittivity dielectric pads improves the local B1+ field and thus the SNR, optimizing TMJ magnetic resonance imaging at 7.0 T. PMID- 26284437 TI - Reduced inorganic sulfur in surface sediment and its impact on benthic environments in offshore areas of NE China. AB - Geochemical cycling and biological toxicity of sulfur in marine sediments is closely related to the activity of organisms. This study investigated the distribution and potential impact on benthic environments of acid volatile sulfur (AVS), chromium(II)-reducible sulfur (CRS), elemental sulfur (ES), total S, C, N and Fe in superficial sediments across the Bohai Sea, Yellow Sea and East China Sea. The composition of reduced inorganic sulfur in the three study areas was dominated by CRS (averaging 72% of total reduced inorganic sulfur). The low AVS content (average of 1.12 MUmol g(-1)) of the sediments and the low values of AVS/CRS (average 0.34 MUmol g(-1)), degree of pyritization and degree of sulphidization indicate that there is sufficient available iron in the sediment to restrict the threat of sulphide toxicity to benthic organisms in most of the study areas. However, high organic matter loads in parts of the study areas have resulted in enhanced accumulation of AVS, resulting in a higher toxicity risk. PMID- 26284438 TI - Muscle Viability Revisited: Are We Removing Normal Muscle? A Critical Evaluation of Dogmatic Debridement. AB - PURPOSE: Determination of muscle viability during debridement is a subjective process with significant consequences. Evaluating muscle color, consistency, contractility, and capacity to bleed (the 4 Cs) was established by a study performed half a century ago. This work reinvestigates the utility of the 4 Cs using current histopathologic techniques. METHODS: After institutional review board approval, 36 biopsies were prospectively collected at a level-1 trauma center from 20 patients undergoing a debridement for open fracture (81%), compartment syndrome (11%), infection (5%), or crush injury (3%). Surgeons graded the biopsies using the 4 Cs, and provided their overall impression as healthy, borderline, or dead. Blinded pathological analysis was performed on each specimen. A correlation between the 4 Cs and surgeon impression with histopathological diagnosis was sought through a univariate statistical analysis. RESULTS: The surgeon's impression was dead muscle in 25 specimens, borderline in 10, and healthy in 1. Pathological analysis of the 35 specimens considered as dead or borderline muscle by the surgeon demonstrated normal muscle or mild interstitial inflammation in 21 specimens (60%). Color (P = 0.07), consistency (P = 0.12), contractility (P = 0.51), capacity to bleed (P = 0.07), and surgeon impression (P = 0.50) were unable to predict histologic appearance. CONCLUSIONS: Neither the 4 Cs nor the surgeon's impression correlate with histological findings regarding muscle viability. In 72% of specimens, the treating surgeon's gross assessment differed from the histopathologic appearance. Although the fate of the debrided muscle remains unclear if left in situ, these results raise questions regarding current practices, including the possibility that surgeons are debriding potentially viable muscle. LEVEL OF EVIDENCE: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence. PMID- 26284439 TI - Percutaneous Anterior Column Fixation for Acetabulum Fractures, Does It Have to Be Difficult?-The New Axial Pedicle View of the Anterior Column for Percutaneous Fixation. AB - Anterior column percutaneous screw fixation can be challenging. The purpose of this new technique is to offer a rapid, simple, and safe method to place an anterior screw. The authors used a 3-dimensional reconstruction simulation, cadaver study, and a clinical case series to demonstrate this new alternative to standard previously described techniques. PMID- 26284440 TI - Bilateral Adenoid Cystic Carcinoma of the Orbit. AB - A 41-year-old woman with adenoid cystic carcinoma of the left lacrimal gland underwent extended left orbital exenteration and postoperative external beam radiation therapy. She presented 1 year postoperatively with contralateral right orbital involvement. The authors report a rare case of adenocystic carcinoma of the lacrimal gland with bilateral orbital involvement. PMID- 26284441 TI - Pressure-Induced Phase Transformation, Reversible Amorphization, and Anomalous Visible Light Response in Organolead Bromide Perovskite. AB - Hydrostatic pressure, as an alternative of chemical pressure to tune the crystal structure and physical properties, is a significant technique for novel function material design and fundamental research. In this article, we report the phase stability and visible light response of the organolead bromide perovskite, CH3NH3PbBr3 (MAPbBr3), under hydrostatic pressure up to 34 GPa at room temperature. Two phase transformations below 2 GPa (from Pm3m to Im3, then to Pnma) and a reversible amorphization starting from about 2 GPa were observed, which could be attributed to the tilting of PbBr6 octahedra and destroying of long-range ordering of MA cations, respectively. The visible light response of MAPbBr3 to pressure was studied by in situ photoluminescence, electric resistance, photocurrent measurements and first-principle simulations. The anomalous band gap evolution during compression with red-shift followed by blue shift is explained by the competition between compression effect and pressure induced amorphization. Along with the amorphization process accomplished around 25 GPa, the resistance increased by 5 orders of magnitude while the system still maintains its semiconductor characteristics and considerable response to the visible light irradiation. Our results not only show that hydrostatic pressure may provide an applicable tool for the organohalide perovskites based photovoltaic device functioning as switcher or controller, but also shed light on the exploration of more amorphous organometal composites as potential light absorber. PMID- 26284442 TI - Palladium-Catalyzed Radical Cascade Iododifluoromethylation/Cyclization of 1,6 Enynes with Ethyl Difluoroiodoacetate. AB - A novel and convenient Pd-catalyzed radical cascade iododifluoromethylation/cyclization of 1,6-enynes with ethyl difluoroiodoacetate is demonstrated. The proposed transformation presents high stereoselectivity under mild and facile reaction conditions, thereby allowing an efficient access to a variety of iodine-containing difluoromethylated pyrrolidines. A possible radical pathway for the transformation is proposed on the basis of the results of control experiments and relevant literature reviews. PMID- 26284444 TI - Paediatric endocrinology: Paradigm shift in genetic testing for neonatal diabetes mellitus--new framework for clinical care. PMID- 26284443 TI - Insights in the ecology and evolutionary history of the Miscellaneous Crenarchaeotic Group lineage. AB - Members of the archaeal Miscellaneous Crenarchaeotic Group (MCG) are among the most successful microorganisms on the planet. During its evolutionary diversification, this very diverse group has managed to cross the saline freshwater boundary, one of the most important evolutionary barriers structuring microbial communities. However, the current understanding on the ecological significance of MCG in freshwater habitats is scarce and the evolutionary relationships between freshwater and saline MCG remains poorly known. Here, we carried out molecular phylogenies using publicly available 16S rRNA gene sequences from various geographic locations to investigate the distribution of MCG in freshwater and saline sediments and to evaluate the implications of saline freshwater transitions during the diversification events. Our approach provided a robust ecological framework in which MCG archaea appeared as a core generalist group in the sediment realm. However, the analysis of the complex intragroup phylogeny of the 21 subgroups currently forming the MCG lineage revealed that distinct evolutionary MCG subgroups have arisen in marine and freshwater sediments suggesting the occurrence of adaptive evolution specific to each habitat. The ancestral state reconstruction analysis indicated that this segregation was mainly due to the occurrence of a few saline-freshwater transition events during the MCG diversification. In addition, a network analysis showed that both saline and freshwater MCG recurrently co-occur with archaea of the class Thermoplasmata in sediment ecosystems, suggesting a potentially relevant trophic connection between the two clades. PMID- 26284445 TI - Therapy: Risk of metformin use in patients with T2DM and advanced CKD. AB - In a new study published in The Lancet Diabetes & Endocrinology, metformin use is associated with significantly increased all-cause mortality in patients with type 2 diabetes mellitus and stage 5 chronic kidney disease (CKD). The findings support current recommendations that metformin should not be used in patients with stage 5 CKD. PMID- 26284446 TI - Paget's disease of bone-genetic and environmental factors. AB - Paget's disease of bone is generally diagnosed in individuals aged >50 years, usually manifests in one or several bones and is initiated by osteoclast-induced osteolytic lesions. Subsequently, over a period of many years, osteoblastic activity can result in sclerosis and deformation of bone. The prevalence of Paget's disease is highest in the UK and in countries where a large number of residents have ancestors from the UK. Currently, in many countries, the prevalence of the disorder has decreased. A considerable number of affected patients have a family history of Paget's disease and the disorder has an autosomal dominant pattern of inheritance but with incomplete penetrance. A large number of mutations in SQSTM1 (which encodes sequestosome-1; also known as ubiquitin-binding protein p62) seem to account for the susceptibility to develop Paget's disease in some families; the involvement of other genes is currently under investigation. In addition to a genetic cause, environmental factors have been proposed to have a role in the pathogenesis of Paget's disease. Although most evidence has been presented for measles virus as an aetiologic factor, some studies have not confirmed its involvement. The decreasing incidence of Paget's disease, which could be attributed to measles vaccination along with the measles virus nucleocapsid protein induction of Paget's disease lesions in transgenic mice, supports an aetiologic role of the virus. PMID- 26284448 TI - Obesity: Bariatric surgery-long-term effects. PMID- 26284447 TI - Preventing and treating foot complications associated with diabetes mellitus. AB - Diabetes mellitus is associated with a series of macrovascular and microvascular changes that can manifest as a wide range of complications. Foot ulcerations affect ~2-4% of patients with diabetes mellitus. Risk factors for foot lesions include peripheral and autonomic neuropathy, vascular disease and previous foot ulceration, as well as other microvascular complications, such as retinopathy and end-stage renal disease. Ulceration is the result of a combination of components that together lead to tissue breakdown. The most frequently occurring causal pathways to the development of foot ulcers include peripheral neuropathy and vascular disease, foot deformity or trauma. Peripheral vascular disease is often not diagnosed in patients with diabetes mellitus until tissue loss is evident, usually in the form of a nonhealing ulcer. Identification of patients with diabetes mellitus who are at high risk of ulceration is important and can be achieved via annual foot screening with subsequent multidisciplinary foot-care interventions. Understanding the factors that place patients with diabetes mellitus at high risk of ulceration, together with an appreciation of the links between different aspects of the disease process, is essential to the prevention and management of diabetic foot complications. PMID- 26284449 TI - Diabetes: Breakfast most important meal of the day, especially for patients with T2DM. PMID- 26284450 TI - Pregnancy: Managing obesity during pregnancy-what are the options? AB - In a new trial, provision of antenatal dietary and lifestyle advice to pregnant women who are obese is associated with modest improvements in maternal diet. This intervention is, however, inadequate to affect pregnancy and birth outcomes, and challenges the notion that limiting gestational weight gain can improve pregnancy outcomes. PMID- 26284451 TI - Correlation of polyunsaturated fatty acids with the cold adaptation of Rhodotorula glutinis. AB - This study aimed to investigate the correlation between the cold adaptation of Rhodotorula glutinis YM25079 and the membrane fluidity, content of polyunsaturated fatty acids and mRNA expression level of the Delta(12)-desaturase gene. The optimum temperature for YM25079 growth was analysed first, then the composition changes of membrane lipid in YM25079 were detected by GC-MS and membrane fluidity was evaluated by 1-anilinonaphthalene-8-sulphonate (ANS) fluorescence. Meanwhile, the encoding sequence of Delta(12)-fatty acid desaturase in YM25079 was cloned and further transformed into Saccharomyces cerevisiae INVScl for functional analysis. The mRNA expression levels of Delta(12)-fatty acid desaturase at 15 degrees C and 25 degrees C were analysed by real-time PCR. YM25079 could grow at 5-30 degrees C, with the optimum temperature of 15 degrees C. The membrane fluidity of YM25079 was not significantly reduced when the culture temperature decreased from 25 degrees C to 15 degrees C, but the content of polyunsaturated fatty acids (PUFAs), including linoleic acid and alpha Linolenic acid increased significantly from 29.4% to 55.39%. Furthermore, a novel Delta(12)-fatty acid desaturase gene YM25079RGD12 from YM25079 was successfully identified and characterized, and the mRNA transcription level of the Delta(12) desaturase gene was about five-fold higher in YM25079 cells grown at 15 degrees C than that at 25 degrees C. These results suggests that the cold adaptation of Rhodotorula glutinis YM25079 might result from higher expression of genes, especially the Delta(12)-fatty acid desaturase gene, during polyunsaturated fatty acids biosynthesis, which increased the content of PUFAs in the cell membrane and maintained the membrane fluidity at low temperature. PMID- 26284452 TI - Bilateral PLA/alginate membranes for the prevention of postsurgical adhesions. AB - A bilateral barrier membrane for the prevention of postsurgical adhesions was developed. Thereby, a smooth PLA side was supposed to keep the affected tissues glidingly separated, while a mucoadhesive side made of alginate was meant to keep the barrier resident on the site of injury so that suturing becomes redundant or at least the membrane stays long enough to facilitate surgical handling. Because hydrophilic alginate and lipophilic PLA films show only low cohesion, solution electrospun meshes of PLA and PLA-PEG-PLA triblock copolymers with varying poly(ethylene glycol) [PEG] content were investigated as cohesion promoter to avoid an easy separation of the functionally different layers. Using direct electrospinning onto the PLA film, a modified contact surface of the mesh was created, which allowed the tested alginate solutions (3%, 5%) to infiltrate to different extents. Thereby, an increasing content of hydrophilic PEG within the mesh copolymer and a lower alginate concentration facilitated the infiltration. As a result, the PLA film with a PLA35k-PEG10k-PLA35k (racemic PLA chains) mesh and an alginate layer cast from a 3% alginate solution appeared to be the most effective combination as examined by means of a t peel test, a mucoadhesion test, a tensile test and optical evaluations. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1563-1570, 2016. PMID- 26284453 TI - The Seated Inactivity Trial (SIT): Physical Activity and Dietary Outcomes Associated With 8 Weeks of Imposed Sedentary Time. AB - BACKGROUND: Sedentary time is an independent risk factor for chronic diseases and mortality. It is unknown whether active adults alter their dietary and/or physical activity behaviors in response to imposed sedentary time, possibly modifying risk. The aim of this study was to determine whether imposed sedentary time would alter typical behaviors of active adults. METHODS: Sixteen physically active, young adults were randomized to the no-intervention control (CON, n = 8) group or the sedentary-intervention (SIT, n = 8) group. SIT participants attended monitored sedentary sessions (8 wk, 10 h/wk). Assessments including diet and physical activity occurred at baseline, week 4, and week 9. RESULTS: There were no differences (P > .05) between CON and SIT groups for step counts or time spent in sedentary, light, moderate, or vigorous physical activity when comparing a week during imposed sedentary time (week 4) to baseline and week 9. At week 4, caloric intake was not different from baseline (P > .05) in either group. Caloric intake decreased significantly (P > .05) in SIT from baseline to week 9. CONCLUSIONS: Active adults did not alter physical activity or dietary behaviors during the imposed sedentary intervention. However, SIT reduced caloric intake from baseline to week 9, indicating a possible compensatory response to imposed sitting in active adults. PMID- 26284454 TI - Reply: To PMID 25559091. PMID- 26284456 TI - Clinical consequences of circulating CD28-negative T cells for solid organ transplantation. AB - CD28 is an important costimulatory molecule expressed on T cells, interacting with CD80 and CD86 on antigen-presenting cells. All naive T cells express CD28, but memory T cells may become CD28 negative (CD28neg) as a result of repetitive cell divisions, the influence of TNF-alpha, and infection with cytomegalovirus. This results in accumulation of CD28neg T cells, which may constitute >50% of the total circulating T-cell population in the elderly. The frequency of CD28neg T cells is associated with diseases such as cancer, autoimmunity, and atherosclerosis in which they may act as either effector or suppressor cells. This functional heterogeneity probably underlies the finding that the CD8posCD28neg T-cell population harbors effector cells mediating acute allograft rejection, but also suppressor cells. The CD4posCD28neg T cells are predominantly considered to be a nonclassical risk factor for atherosclerotic disease, and their contribution to alloreactivity is less clear. CD28neg T cells depend on IL 15 for their proliferation, and they have increased the expression of specific costimulatory molecules, such as NK receptors, TNF-alpha receptor family members, and the adhesion/costimulatory molecule CD2. Targeting these costimulatory pathways presents potential therapeutic options to block allograft rejection mediated by CD28neg T cells which are resistant to belatacept. PMID- 26284455 TI - miRNAs as Biomarkers in Chronic Myelogenous Leukemia. AB - Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm that is frequently characterized by the constitutive expression of the oncogenic protein BCR-ABL tyrosine kinase. Tyrosine kinase inhibitors (TKIs) targeting breakpoint cluster region-ABL are the first-line therapy for most CML patients and have drastically improved the prognosis of CML. However, some CML patients are unresponsive to TKI treatment, and a notable proportion of initially responsive patients develop drug resistance. Several molecular pathways have been correlated with resistance to TKI treatment, however, the exact mechanism of developing drug resistance remains ambiguous. Recently, microRNAs (miRNAs) have been implicated in the progression of CML and the development of resistance to TKI treatment based on their important regulatory function in cell homeostasis, and the deregulation observed in the initiation and progression of many leukemia subtypes. In this review, we summarize some of the major discoveries regarding miRNAs in CML, and their relevance as biomarkers for diagnosis, disease progression, and drug sensitivity. PMID- 26284458 TI - Autonomic modulation analysis in active and sedentary kidney transplanted recipients. AB - Modulation of the autonomic nervous system on heart rate can be compromised in chronic kidney disease and may result in changes in the frequency and duration of the cardiac cycle. The aim of this study was to evaluate autonomic modulation in active and sedentary renal transplant recipients. Twenty renal-transplanted individuals were analyzed at the Centro de Prevencao de Doencas Renais (Kidney Disease Education Centre), in the academic hospital of Universidade Federal do Maranhao, and were divided into the active group (AG) and the sedentary group (SG). The AG comprised of six men and four women (age 43.10 +/- 13.02) and was in regular concurrent training intervention for 8 weeks, while the SG was composed of three men and seven women (age 36.8 +/- 9.26). Analysis of heart rate (HR) variability in time and frequency domain demonstrated that HR mean values in the SG and AG were 787.32 +/- 79.60 and 870 +/- 106.66 ms, respectively. Differences were observed in the time domain and frequency domain. The total index of low frequency and high frequency showed no differences between the SG and AG. Biochemical variables presented significantly lower levels after 8 weeks of training. Higher heart rate variability in the time domain and greater vagal modulation was observed in the AG. The AG ad greater vagal modulation when compared to the SG, with removal of the sympathetic and increased parasympathetic in the behaviour was confirmed by sympatho-vagal balance. The AG also presented significant improvements in the frequency domain. PMID- 26284459 TI - Williamson Ether Synthesis with Phenols at a Tertiary Stereogenic Carbon: Formal Enantioselective Phenoxylation of beta-Keto Esters. AB - The enantioselective formation of alpha-aryloxy-beta-keto esters is described for the first time. Lewis acid catalyzed enantioselective chlorination of beta-keto esters and subsequent SN 2 reactions with phenols yielded alpha-aryloxy-beta-keto esters with up to 96% ee. Favorskii rearrangement of alpha-chloro-beta-keto esters was also found to give 1,2-diesters with slightly reduced enantiopurity. PMID- 26284460 TI - Cost-utility analysis of an advanced pressure ulcer management protocol followed by trained wound, ostomy, and continence nurses. AB - The high prevalence of severe pressure ulcers (PUs) is an important issue that requires to be highlighted in Japan. In a previous study, we devised an advanced PU management protocol to enable early detection of and intervention for deep tissue injury and critical colonization. This protocol was effective for preventing more severe PUs. The present study aimed to compare the cost effectiveness of the care provided using an advanced PU management protocol, from a medical provider's perspective, implemented by trained wound, ostomy, and continence nurses (WOCNs), with that of conventional care provided by a control group of WOCNs. A Markov model was constructed for a 1-year time horizon to determine the incremental cost-effectiveness ratio of advanced PU management compared with conventional care. The number of quality-adjusted life-years gained, and the cost in Japanese yen (Y) ($US1 = Y120; 2015) was used as the outcome. Model inputs for clinical probabilities and related costs were based on our previous clinical trial results. Univariate sensitivity analyses were performed. Furthermore, a Bayesian multivariate probability sensitivity analysis was performed using Monte Carlo simulations with advanced PU management. Two different models were created for initial cohort distribution. For both models, the expected effectiveness for the intervention group using advanced PU management techniques was high, with a low expected cost value. The sensitivity analyses suggested that the results were robust. Intervention by WOCNs using advanced PU management techniques was more effective and cost-effective than conventional care. PMID- 26284462 TI - Evolutionary processes driving spatial patterns of intraspecific genetic diversity in river ecosystems. AB - Describing, understanding and predicting the spatial distribution of genetic diversity is a central issue in biological sciences. In river landscapes, it is generally predicted that neutral genetic diversity should increase downstream, but there have been few attempts to test and validate this assumption across taxonomic groups. Moreover, it is still unclear what are the evolutionary processes that may generate this apparent spatial pattern of diversity. Here, we quantitatively synthesized published results from diverse taxa living in river ecosystems, and we performed a meta-analysis to show that a downstream increase in intraspecific genetic diversity (DIGD) actually constitutes a general spatial pattern of biodiversity that is repeatable across taxa. We further demonstrated that DIGD was stronger for strictly waterborne dispersing than for overland dispersing species. However, for a restricted data set focusing on fishes, there was no evidence that DIGD was related to particular species traits. We then searched for general processes underlying DIGD by simulating genetic data in dendritic-like river systems. Simulations revealed that the three processes we considered (downstream-biased dispersal, increase in habitat availability downstream and upstream-directed colonization) might generate DIGD. Using random forest models, we identified from simulations a set of highly informative summary statistics allowing discriminating among the processes causing DIGD. Finally, combining these discriminant statistics and approximate Bayesian computations on a set of twelve empirical case studies, we hypothesized that DIGD were most likely due to the interaction of two of these three processes and that contrary to expectation, they were not solely caused by downstream-biased dispersal. PMID- 26284461 TI - Prolonged outbreak of adenovirus A31 in allogeneic stem cell transplant recipients. AB - BACKGROUND: An outbreak of human adenovirus (HAdV) A31 occurred from December 2011 to March 2012 at the Center for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital in Sweden. We analyzed the outbreak, the routes of transmission, and report the medical consequences. METHODS: The medical records of all patients admitted to CAST during the outbreak period were studied. Phylogenetic analysis of the patient HAdV strains was performed by sequencing the hexon gene and the more variable E3 gene. RESULTS: We identified 9 cases of HAdV A31. Hygiene measures were implemented, but transmission continued for 2 months. All 9 patients had been admitted to the ward, but 2 had no connection in time to other known HAdV A31 cases. DNA sequencing of the patient strains strongly suggested nosocomial transmission. Transplantation was postponed and then cancelled in 1 patient, and 5 patients were treated with cidofovir because of high levels of viremia. In 7 patients, concomitant graft-versus-host disease (GVHD) grade II-V complicated the clinical picture, as it was difficult to distinguish symptoms of GVHD from those of HAdV infection. CONCLUSION: An outbreak of HAdV in HSCT recipients can be difficult to control. Although none of the patients had severe disease, the medical consequences were significant. It is possible that unidentified cases with mild symptoms may have caused continuous transmission at the unit. Regular testing of all patients several weeks beyond the last case identified may be an important measure to control transmission. PMID- 26284463 TI - Prevalence of interdigital psoriasis of the feet ("psoriasis alba") in mild, moderate, and severe psoriasis. AB - Interdigital psoriasis of the feet ("psoriasis alba") is a rare form of inverse psoriasis. We conducted a cross-sectional study of the prevalence of interdigital psoriasis in mild, moderate, and severe psoriasis, compared to atopic dermatitis and normal controls. Data were collected during 2010-2013 from 232 psoriatic patients, 190 patients with atopic dermatitis, and 202 normal controls. The psoriatic and atopic dermatitis patients were from the dermatology department and outpatient clinic of the Hadassah-Hebrew University Medical Center in Jerusalem, Israel. The normal controls were healthy workers and volunteers from Hadassah Hospital who were not aware of any dermatological disease and had never consulted a general practitioner or dermatologist for skin problems of the feet. Our study revealed a prevalence of 2.6% of interdigital psoriasis of the feet in psoriatic patients, especially in men, and none in atopic dermatitis and normal controls. Three of the six affected patients with interdigital psoriasis of the feet complained of itching, both feet were involved in four patients, while two presented with additional palmoplantar psoriasis. The hematoxylin and eosin histopathological findings were in line with those found in inverse psoriasis. Dermatologists should be aware of this entity and treat it correctly. The diagnosis should be considered in psoriatic patients presenting with whitish plaque or patches in the toe-webs, in whom the fungal test is negative and are not responding to antimycotic treatment. PMID- 26284464 TI - Rheumatoid nodulosis with extra-articular cyst synovitis. PMID- 26284465 TI - The effect of genetic test-based risk information on behavioral outcomes: A critical examination of failed trials and a call to action. AB - Encouraging individuals at risk for common complex disease like heart disease, cancer, and diabetes to adopt lifestyle changes (e.g., smoking cessation, exercise, proper nutrition, increased screening) could be powerful public health tools to decrease the enormous personal and economic burden of these conditions. Theoretically, genetic risk information appears to be a compelling tool that could be used to provoke at-risk individuals to adopt these lifestyle changes. Unfortunately, however, numerous studies now have shown that providing individuals with genetic test-based risk information has little to no impact on their behavior. In this article (a commentary not a systematic review), the failed trials in which genetic information has been used as a tool to induce behavior change will be critically examined in order to identify new and potentially more effective ways forward. PMID- 26284466 TI - miRNA for diagnosis and clinical implications of human hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies, as a result of being asymptomatic at early stage, subsequent late clinical confirmation and poor prognosis. It is urgent to search more accurate biomarkers for diagnosing early HCC and predicting prognosis. Many factors participate in liver carcinogenesis, including dysregulation of miRNA. miRNA were endogenously expressed non-coding single-stranded small RNA with 19-25 nucleotides. Accumulating evidences have showed that miRNA from circulation and solitary tumors may be useful to classify the differentiation degree and stages of HCC, detect the hepatitis B/C virus-related HCC, and predict the survival rate after surgical resection or orthotopic liver transplantation. In this review, we summarize dysregulated miRNA, their roles in diagnosis and clinical implications of HCC. PMID- 26284467 TI - Co-evolution of lymphocyte receptors with MHC class I. PMID- 26284469 TI - Activation of human T cells by CD1 and self-lipids. AB - Over two decades ago, it was discovered that the human T-cell repertoire contains T cells that do not recognize peptide antigens in the context of MHC molecules but instead respond to lipid antigens presented by CD1 antigen-presenting molecules. The ability of T cells to 'see' lipid antigens bound to CD1 enables these lymphocytes to sense changes in the lipid composition of cells and tissues as a result of infections, inflammation, or malignancies. Although foreign lipid antigens have been shown to function as antigens for CD1-restricted T cells, many CD1-restricted T cells do not require foreign antigens for activation but instead can be activated by self-lipids presented by CD1. This review highlights recent developments in the field, including the identification of common mammalian lipids that function as autoantigens for alphabeta and gammadelta T cells, a novel mode of T-cell activation whereby CD1a itself rather than lipids serves as the autoantigen, and various mechanisms by which the activation of CD1 autoreactive T cells is regulated. As CD1 can induce T-cell effector functions in the absence of foreign antigens, multiple mechanisms are in place to regulate this self-reactivity, and stimulatory CD1-lipid complexes appear to be tightly controlled in space and time. PMID- 26284471 TI - Co-evolution with chicken class I genes. AB - The concept of co-evolution (or co-adaptation) has a long history, but application at molecular levels (e.g., 'supergenes' in genetics) is more recent, with a consensus definition still developing. One interesting example is the chicken major histocompatibility complex (MHC). In contrast to typical mammals that have many class I and class I-like genes, only two classical class I genes, two CD1 genes and some non-classical Rfp-Y genes are known in chicken, and all are found on the microchromosome that bears the MHC. Rarity of recombination between the closely linked and polymorphic genes encoding classical class I and TAPs allows co-evolution, leading to a single dominantly expressed class I molecule in each MHC haplotype, with strong functional consequences in terms of resistance to infectious pathogens. Chicken tapasin is highly polymorphic, but co evolution with TAP and class I genes remains unclear. T-cell receptors, natural killer (NK) cell receptors, and CD8 co-receptor genes are found on non-MHC chromosomes, with some evidence for co-evolution of surface residues and number of genes along the avian and mammalian lineages. Over even longer periods, co evolution has been invoked to explain how the adaptive immune system of jawed vertebrates arose from closely linked receptor, ligand, and antigen-processing genes in the primordial MHC. PMID- 26284468 TI - Coevolution of MHC genes (LMP/TAP/class Ia, NKT-class Ib, NKp30-B7H6): lessons from cold-blooded vertebrates. AB - Comparative immunology provides the long view of what is conserved across all vertebrate taxa versus what is specific to particular organisms or group of organisms. Regarding the major histocompatibility complex (MHC) and coevolution, three striking cases have been revealed in cold-blooded vertebrates: lineages of class Ia antigen-processing and -presenting genes, evolutionary conservation of NKT-class Ib recognition, and the ancient emergence of the natural cytotoxicity receptor NKp30 and its ligand B7H6. While coevolution of transporter associated with antigen processing (TAP) and class Ia has been documented in endothermic birds and two mammals, lineages of LMP7 are restricted to ectotherms. The unambiguous discovery of natural killer T (NKT) cells in Xenopus demonstrated that NKT cells are not restricted to mammals and are likely to have emerged at the same time in evolution as classical alpha/beta and gamma/delta T cells. NK cell receptors evolve at a rapid rate, and orthologues are nearly impossible to identify in different vertebrate classes. By contrast, we have detected NKp30 in all gnathostomes, except in species where it was lost. The recently discovered ligand of NKp30, B7H6, shows strong signs of coevolution with NKp30 throughout evolution, i.e. coincident loss or expansion of both genes in some species. NKp30 also offers an attractive IgSF candidate for the invasion of the RAG transposon, which is believed to have initiated T-cell receptor/immunoglobulin adaptive immunity. Besides reviewing these intriguing features of MHC evolution and coevolution, we offer suggestions for future studies and propose a model for the primordial or proto MHC. PMID- 26284472 TI - Comparative genomics of the NKG2D ligand gene family. AB - NKG2D ligands (NKG2DLs) are a group of stress-inducible major histocompatibility complex (MHC) class I-like molecules that act as a danger signal alerting the immune system to the presence of abnormal cells. In mammals, two families of NKG2DL genes have been identified: the MIC gene family encoded in the MHC region and the ULBP gene family encoded outside the MHC region in most species. Some mammals have a third family of NKG2DL-like class I genes which we named MILL (MHC class I-like located near the leukocyte receptor complex). Despite the fact that MILL genes are more closely related to MIC genes than ULBP genes are to MIC genes, MILL molecules do not function as NKG2DLs, and their function remains unknown. With the progress of mammalian genome projects, information on the MIC, ULBP, and MILL gene families became available in many mammalian species. Here, we summarize such information and discuss the origin and evolution of the NKG2DL gene family from the viewpoint of host-pathogen coevolution. PMID- 26284473 TI - Genetics, genomics, and evolutionary biology of NKG2D ligands. AB - Human and mouse NKG2D ligands (NKG2DLs) are absent or only poorly expressed by most normal cells but are upregulated by cell stress, hence, alerting the immune system in case of malignancy or infection. Although these ligands are numerous and highly variable (at genetic, genomic, structural, and biochemical levels), they all belong to the major histocompatibility complex class I gene superfamily and bind to a single, invariant, receptor: NKG2D. NKG2D (CD314) is an activating receptor expressed on NK cells and subsets of T cells that have a key role in the recognition and lysis of infected and tumor cells. Here, we review the molecular diversity of NKG2DLs, discuss the increasing appreciation of their roles in a variety of medical conditions, and propose several explanations for the evolutionary force(s) that seem to drive the multiplicity and diversity of NKG2DLs while maintaining their interaction with a single invariant receptor. PMID- 26284474 TI - Surveillance of cell and tissue perturbation by receptors in the LRC. AB - The human leukocyte receptor complex (LRC) encompasses several sets of genes with a common evolutionary origin and which form a branch of the immunoglobulin superfamily (IgSF). Comparisons of LRC genes both within and between species calls for a high degree of plasticity. The drive for this unprecedented level of variation is not known, but it relates in part to interaction of several LRC products with polymorphic human leukocyte antigen (HLA) class I molecules. However, the range of other proposed ligands for LRC products indicates a dynamic set of receptors that have adapted to detect target molecules relating to numerous cellular pathways. Several receptors in the complex bind a molecular signature in collagenous ligands. Others detect a variety of motifs relating to pathogens in addition to cellular stress, attesting to the opportunistic versatility of LRC receptors. PMID- 26284475 TI - Ly49 receptors: evolution, genetic diversity, and impact on immunity. AB - Natural killer (NK) cells express cell surface receptors that recognize class I major histocompatibility complex (MHC-I) molecules to distinguish between healthy and unhealthy cells. The multigenic and polymorphic nature of the MHC-I genes has influenced the convergent evolution of similarly polymorphic and diversified NK cell receptor families: the C-type lectin-like Ly49 receptors in mice, and the killer cell immunoglobulin-like receptors (KIRs) in humans. Although structurally distinct, both receptor families have similar functions in terms of MHC-I recognition and downstream signal transduction, and they regulate multiple aspects of NK cell biology during development and after maturation as fully differentiated and functionally competent cells. The Ly49 gene locus has undergone rapid, lineage-specific expansions and contractions resulting in multiple distinct haplotypes of variable gene number, allelic diversity, and MHC I ligand specificity. This in turn has influenced the type and degree of Ly49 receptor expression on NK cells, and their contribution to immunity in different mouse strains. In this review, we have attempted to describe the evolutionary processes that have shaped strain-specific Ly49 receptor repertoires, and their impact on NK cell functions during health and disease. PMID- 26284470 TI - Coevolution of T-cell receptors with MHC and non-MHC ligands. AB - The structure and amino acid diversity of the T-cell receptor (TCR), similar in nature to that of Fab portions of antibodies, would suggest that these proteins have a nearly infinite capacity to recognize antigen. Yet all currently defined native T cells expressing an alpha and beta chain in their TCR can only sense antigen when presented in the context of a major histocompatibility complex (MHC) molecule. This MHC molecule can be one of many that exist in vertebrates, presenting small peptide fragments, lipid molecules, or small molecule metabolites. Here we review the pattern of TCR recognition of MHC molecules throughout a broad sampling of species and T-cell lineages and also touch upon T cells that do not appear to require MHC presentation for their surveillance function. We review the diversity of MHC molecules and information on the corresponding T-cell lineages identified in divergent species. We also discuss TCRs with structural domains unlike that of conventional TCRs of mouse and human. By presenting this broad view of TCR sequence, structure, domain organization, and function, we seek to explore how this receptor has evolved across time and been selected for alternative antigen-recognition capabilities in divergent lineages. PMID- 26284476 TI - A bird's eye view of NK cell receptor interactions with their MHC class I ligands. AB - The surveillance of target cells by natural killer (NK) cells utilizes an ensemble of inhibitory and activating receptors, many of which interact with major histocompatibility complex (MHC) class I molecules. NK cell recognition of MHC class I proteins is important developmentally for the acquisition of full NK cell effector capacity and during target cell recognition, where the engagement of inhibitory receptors and MHC class I molecules attenuates NK cell activation. Human NK cells have evolved two broad strategies for recognition of human leukocyte antigen (HLA) class I molecules: (i) direct recognition of polymorphic classical HLA class I proteins by diverse receptor families such as the killer cell immunoglobulin-like receptors (KIRs), and (ii) indirect recognition of conserved sets of HLA class I-derived peptides displayed on the non-classical HLA E for recognition by CD94-NKG2 receptors. In this review, we assess the structural basis for the interaction between these NK receptors and their HLA class I ligands and, using the suite of published KIR and CD94-NKG2 ternary complexes, highlight the features that allow NK cells to orchestrate the recognition of a range of different HLA class I proteins. PMID- 26284477 TI - Selection, tuning, and adaptation in mouse NK cell education. AB - Natural killer (NK) cells recognize transformed cells with an array of germline encoded inhibitory and activating receptors. Inhibitory Ly49 receptors bind major histocompatibility complex class I (MHC-I) molecules, providing a mechanism by which NK cells maintain self-tolerance yet eliminate cells expressing reduced levels of MHC-I. Additionally, MHC-I molecules are required for NK cell education, a process in which NK cells acquire responsiveness. In this review, we discuss three facets of MHC class I-dependent education of mouse NK cells: skewing of the inhibitory receptor repertoire, induction of functional responsiveness, and tuning in response to changes in MHC-I expression. We discuss prevailing models for education such as licensing and disarming and propose a model for positive selection of 'useful' NK cell subsets. Furthermore, we argue that both repertoire skewing and functional NK cell education may be altered in mature NK cells subject to changes in MHC-I input and suggest that this process may provide increased dynamics to the NK cell system. PMID- 26284478 TI - Human KIR repertoires: shaped by genetic diversity and evolution. AB - Killer cell immunoglobulin-like receptors (KIRs) on natural killer (NK) cells are crucially involved in the control of cancer development and virus infection by probing cells for proper expression of HLA class I. The clonally distributed expression of KIRs leads to great combinatorial diversity that develops in the presence of the evolutionary older CD94/NKG2A receptor to create highly stochastic but tolerant repertoires of NK cells. These repertoires are present at birth and are subsequently shaped by an individuals' immunological history toward recognition of self. The single most important factor that shapes functional NK cell repertoires is the genetic diversity of KIR, which is characterized by the presence of group A and B haplotypes with complementary gene content that are present in all human populations. Group A haplotypes constitute the minimal genetic entity that provides high affinity recognition of all major human leukocyte antigen class I-encoded ligands, whereas group B haplotypes contribute to the diversification of NK cell repertoires by providing sets of stimulatory KIR genes that modify NK cell responses. We suggest a cooperative model for the balancing selection of A and B haplotypes, which is driven by the need to provide a suitable corridor of repertoire complexity in which A/A individuals with only 16 different KIR combinations coexist with A/B and B/B donors expressing up to 2048 different clone types. PMID- 26284480 TI - NK cells: tuned by peptide? AB - Natural killer cells express multiple receptors for major histocompatibility complex (MHC) class I, including the killer cell immunoglobulin-like receptors (KIRs) and the C-type lectin-like CD94:NKG2 receptors. The KIR locus is extremely polymorphic, paralleling the diversity of its classical MHC class I ligands. Similarly, the conservation of the NKG2 family of receptors parallels the conservation of MHC-E, the ligand for CD94:NKG2A/C/E. Binding of both CD94:NKG2 heterodimers and KIR to their respective MHC class I ligand is peptide dependent, and despite the evolution of these receptors, they have retained the property of peptide selectivity. Such peptide selectivity affects these two systems in different ways. HLA-E binding non-inhibitory peptides augment inhibition at CD94:NKG2A, while HLA-C binding non-inhibitory peptides antagonize inhibition at KIR2DL2/3, implying that KIRs are specialized to respond positively to changes in peptide repertoire. Thus, while specific KIRs, such as KIR2DL3, are associated with beneficial outcomes from viral infections, viral peptides augment inhibition at CD94:NKGA. Conversely, NKG2A-positive NK cells sense MHC class I downregulation more efficiently than KIRs. Thus, these two receptor:ligand systems appear to have complementary functions in recognizing changes in MHC class I. PMID- 26284479 TI - Newtonian cell interactions shape natural killer cell education. AB - Newton's third law of motion states that for every action on a physical object there is an equal and opposite reaction. The dynamic change in functional potential of natural killer (NK) cells during education bears many features of such classical mechanics. Cumulative physical interactions between cells, under a constant influence of homeostatic drivers of differentiation, lead to a reactive spectrum that ultimately shapes the functionality of each NK cell. Inhibitory signaling from an array of self-specific receptors appear not only to suppress self-reactivity but also aid in the persistence of effector functions over time, thereby allowing the cell to gradually build up a functional potential. Conversely, the frequent non-cytolytic interactions between normal cells in the absence of such inhibitory signaling result in continuous stimulation of the cells and attenuation of effector function. Although an innate cell, the degree to which the fate of the NK cell is predetermined versus its ability to adapt to its own environment can be revealed through a Newtonian view of NK cell education, one which is both chronological and dynamic. As such, the development of NK cell functional diversity is the product of qualitatively different physical interactions with host cells, rather than simply the sum of their signals or an imprint based on intrinsically different transcriptional programs. PMID- 26284481 TI - Co-evolution of the MHC class I and KIR gene families in rhesus macaques: ancestry and plasticity. AB - Researchers dealing with the human leukocyte antigen (HLA) class I and killer immunoglobulin receptor (KIR) multi-gene families in humans are often wary of the complex and seemingly different situation that is encountered regarding these gene families in Old World monkeys. For the sake of comparison, the well-defined and thoroughly studied situation in humans has been taken as a reference. In macaques, both the major histocompatibility complex class I and KIR gene families are plastic entities that have experienced various rounds of expansion, contraction, and subsequent recombination processes. As a consequence, haplotypes in macaques display substantial diversity with regard to gene copy number variation. Additionally, for both multi-gene families, differential levels of polymorphism (allelic variation), and expression are observed as well. A comparative genetic approach has allowed us to answer questions related to ancestry, to shed light on unique adaptations of the species' immune system, and to provide insights into the genetic events and selective pressures that have shaped the range of these gene families. PMID- 26284482 TI - The killer-cell immunoglobulin-like receptors of macaques. AB - Natural killer (NK) cells play a central role in immune responses through direct cytotoxicity and the release of cytokines that prime adaptive immunity. In simian primates, NK cell responses are regulated by interactions between two highly polymorphic sets of molecules: the killer-cell immunoglobulin-like receptors (KIRs) and their major histocompatibility complex (MHC) class I ligands. KIR-MHC class I interactions in humans have been implicated in the outcome of a number viral diseases and cancers. However, studies to address the role of KIRs in animal models have been limited by the complex immunogenetics and lack of defined ligands for KIRs in non-human primates. Due to the rapid evolution of KIRs, there is little conservation among the KIR genes of different primate species and it is not possible to predict the specificity of KIRs from known KIR-MHC class I interactions in humans. Hence, the MHC class I ligands for KIRs in species other than humans are poorly defined. Here, we review the KIR genes of the rhesus macaque, an important animal model for human immunodeficiency virus infection and other infectious diseases, and the MHC class I ligands that have been identified for KIRs in this species. PMID- 26284484 TI - Co-evolution of NK receptors and HLA ligands in humans is driven by reproduction. AB - Allogeneic individuals co-exist during pregnancy in eutherian mammals. Maternal and fetal cells intermingle at the site of placental attachment in the uterus, where the arteries are remodeled to supply the fetus with oxygen and nutrients. This access by placental cells to the maternal supply line determines the growth and birth weight of the baby and is subject to stabilizing selection. Invading placental trophoblast cells express human leukocyte antigen class I ligands (HLA E, HLA-G, and HLA-C) for receptors on maternal uterine natural killer (NK) and myelomonocytic cells, CD94/NKG2, leukocyte immunoglobulin-like receptor (LILR), and killer immunoglobulin receptor (KIR). Of these, only the KIR/HLA-C system is highly polymorphic. Different combinations of maternal KIR and fetal HLA-C variants are correlated with low birth weight and pre-eclampsia or high birth weight and obstructed labor, the two extremes of the obstetric dilemma. This situation has arisen because of the evolution of bipedalism and subsequently, in the last million years, larger brains. At this point, the human system began to reach a balance between KIR A and KIR B haplotypes and C1 and C2 epitopes of HLA C alleles that reflects a functional compromise between the competing demands of immunity and reproduction. PMID- 26284483 TI - Co-evolution of MHC class I and variable NK cell receptors in placental mammals. AB - Shaping natural killer (NK) cell functions in human immunity and reproduction are diverse killer cell immunoglobulin-like receptors (KIRs) that recognize polymorphic MHC class I determinants. A survey of placental mammals suggests that KIRs serve as variable NK cell receptors only in certain primates and artiodactyls. Divergence of the functional and variable KIRs in primates and artiodactyls predates placental reproduction. Among artiodactyls, cattle but not pigs have diverse KIRs. Catarrhine (humans, apes, and Old World monkeys) and platyrrhine (New World monkeys) primates, but not prosimians, have diverse KIRs. Platyrrhine and catarrhine systems of KIR and MHC class I are highly diverged, but within the catarrhines, a stepwise co-evolution of MHC class I and KIR is discerned. In Old World monkeys, diversification focuses on MHC-A and MHC-B and their cognate lineage II KIR. With evolution of C1-bearing MHC-C from MHC-B, as informed by orangutan, the focus changes to MHC-C and its cognate lineage III KIR. Evolution of C2 from C1 and fixation of MHC-C drove further elaboration of MHC-C-specific KIR, as exemplified by chimpanzee. In humans, the evolutionary trajectory changes again. Emerging from reorganization of the KIR locus and selective attenuation of KIR avidity for MHC class I are the functionally distinctive KIR A and KIR B haplotypes. PMID- 26284485 TI - Brief-exposure to preoperative bevacizumab reveals a TGF-beta signature predictive of response in HER2-negative breast cancers. AB - To best define biomarkers of response, and to shed insight on mechanism of action of certain clinically important agents for early breast cancer, we used a brief exposure paradigm in the preoperative setting to study transcriptional changes in patient tumors that occur with one dose of therapy prior to combination chemotherapy. Tumor biopsies from breast cancer patients enrolled in two preoperative clinical trials were obtained at baseline and after one dose of bevacizumab (HER2-negative), trastuzumab (HER2-positive) or nab-paclitaxel, followed by treatment with combination chemo-biologic therapy. RNA-Sequencing based PAM50 subtyping at baseline of 46 HER2-negative patients revealed a strong association between the basal-like subtype and pathologic complete response (pCR) to chemotherapy plus bevacizumab (p <= 0.0027), but did not provide sufficient specificity to predict response. However, a single dose of bevacizumab resulted in down-regulation of a well-characterized TGF-beta activity signature in every single breast tumor that achieved pCR (p <= 0.004). The TGF-beta signature was confirmed to be a tumor-specific read-out of the canonical TGF-beta pathway using pSMAD2 (p <= 0.04), with predictive power unique to brief-exposure to bevacizumab (p <= 0.016), but not trastuzumab or nab-paclitaxel. Down-regulation of TGF-beta activity was associated with reduction in tumor hypoxia by transcription and protein levels, suggesting therapy-induced disruption of an autocrine-loop between tumor stroma and malignant cells. Modulation of the TGF-beta pathway upon brief-exposure to bevacizumab may provide an early functional readout of pCR to preoperative anti-angiogenic therapy in HER2-negative breast cancer, thus providing additional avenues for exploration in both preclinical and clinical settings with these agents. PMID- 26284486 TI - Exosomal levels of miRNA-21 from cerebrospinal fluids associated with poor prognosis and tumor recurrence of glioma patients. AB - Glioma is a most common type of primary brain tumors. Extracellular vesicles, in the form of exosomes, are known to mediate cell-cell communication by transporting cell-derived proteins and nucleic acids, including various microRNAs (miRNAs). Here we examined the cerebrospinal fluid (CSF) from patients with recurrent glioma for the levels of cancer-related miRNAs, and evaluated the values for prognosis by comparing the measures of CSF-, serum-, and exosome contained miR-21 levels. Samples from seventy glioma patients following surgery were compared with those from brain trauma patients as a non-tumor control group. Exosomal miR-21 levels in the CSF of glioma patients were found significantly higher than in the controls; whereas no difference was detected in serum-derived exosomal miR-21 expression. The CSF-derived exosomal miR-21 levels correlated with tumor spinal/ventricle metastasis and the recurrence with anatomical site preference. From additional 198 glioma tissue samples, we verified that miR-21 levels associated with tumor grade of diagnosis and negatively correlated with the median values of patient overall survival time. We further used a lentiviral inhibitor to suppress miR-21 expression in U251 cells. The results showed that the levels of miR-21 target genes of PTEN, RECK and PDCD4 were up-regulated at protein levels. Therefore, we concluded that the exosomal miR-21 levels could be demonstrated as a promising indicator for glioma diagnosis and prognosis, particularly with values to predict tumor recurrence or metastasis. PMID- 26284487 TI - Simultaneous inhibition of multiple oncogenic miRNAs by a multi-potent microRNA sponge. AB - The roles of oncogenic miRNAs are widely recognized in many cancers. Inhibition of single miRNA using antagomiR can efficiently knock-down a specific miRNA. However, the effect is transient and often results in subtle phenotype, as there are other miRNAs contribute to tumorigenesis. Here we report a multi-potent miRNA sponge inhibiting multiple miRNAs simultaneously. As a model system, we targeted miR-21, miR-155 and miR-221/222, known as oncogenic miRNAs in multiple tumors including breast and pancreatic cancers. To achieve efficient knockdown, we generated perfect and bulged-matched miRNA binding sites (MBS) and introduced multiple copies of MBS, ranging from one to five, in the multi-potent miRNA sponge. Luciferase reporter assay showed the multi-potent miRNA sponge efficiently inhibited 4 miRNAs in breast and pancreatic cancer cells. Furthermore, a stable and inducible version of the multi-potent miRNA sponge cell line showed the miRNA sponge efficiently reduces the level of 4 target miRNAs and increase target protein level of these oncogenic miRNAs. Finally, we showed the miRNA sponge sensitize cells to cancer drug and attenuate cell migratory activity. Altogether, our study demonstrates the multi-potent miRNA sponge is a useful tool to examine the functional impact of simultaneous inhibition of multiple miRNAs and proposes a therapeutic potential. PMID- 26284489 TI - Thermal Conduction in Vertically Aligned Copper Nanowire Arrays and Composites. AB - The ability to efficiently and reliably transfer heat between sources and sinks is often a bottleneck in the thermal management of modern energy conversion technologies ranging from microelectronics to thermoelectric power generation. These interfaces contribute parasitic thermal resistances that reduce device performance and are subjected to thermomechanical stresses that degrade device lifetime. Dense arrays of vertically aligned metal nanowires (NWs) offer the unique combination of thermal conductance from the constituent metal and mechanical compliance from the high aspect ratio geometry to increase interfacial heat transfer and device reliability. In the present work, we synthesize copper NW arrays directly onto substrates via templated electrodeposition and extend this technique through the use of a sacrificial overplating layer to achieve improved uniformity. Furthermore, we infiltrate the array with an organic phase change material and demonstrate the preservation of thermal properties. We use the 3omega method to measure the axial thermal conductivity of freestanding copper NW arrays to be as high as 70 W m(-1) K(-1), which is more than an order of magnitude larger than most commercial interface materials and enhanced conductivity nanocomposites reported in the literature. These arrays are highly anisotropic, and the lateral thermal conductivity is found to be only 1-2 W m(-1) K(-1). We use these measured properties to elucidate the governing array-scale transport mechanisms, which include the effects of morphology and energy carrier scattering from size effects and grain boundaries. PMID- 26284488 TI - Colorectal cancer-promoting activity of the senescent peritoneal mesothelium. AB - Gastrointestinal cancers metastasize into the peritoneal cavity in a process controlled by peritoneal mesothelial cells (HPMCs). In this paper we examined if senescent HPMCs can intensify the progression of colorectal (SW480) and pancreatic (PSN-1) cancers in vitro and in vivo. Experiments showed that senescent HPMCs stimulate proliferation, migration and invasion of SW480 cells, and migration of PSN-1 cells. When SW480 cells were injected i.p. with senescent HPMCs, the dynamics of tumor formation and vascularization were increased. When xenografts were generated using PSN-1 cells, senescent HPMCs failed to favor their growth. SW480 cells subjected to senescent HPMCs displayed up-regulated expression of transcripts for various pro-cancerogenic agents as well as increased secretion of their products. Moreover, they underwent an epithelial mesenchymal transition in the Smad 2/3-Snail1-related pathway. The search for mediators of senescent HPMC activity showed that increased SW480 cell proliferation was stimulated by IL-6, migration by CXCL8 and CCL2, invasion by IL 6, MMP-3 and uPA, and epithelial-mesenchymal transition by TGF-beta1. Secretion of these agents by senescent HPMCs was increased in an NF-kappaB- and p38 MAPK dependent mechanism. Collectively, our findings indicate that in the peritoneum senescent HPMCs may create a metastatic niche in which critical aspects of cancer progression become intensified. PMID- 26284490 TI - Non-toxigenic tox gene-bearing Corynebacterium ulcerans in a traumatic ulcer from a human case and his asymptomatic dog. AB - A non-toxigenic tox gene-bearing (NTTB) Corynebacterium ulcerans was grown from the wound of a 61-year-old gardener and in a nasal specimen from the patient's asymptomatic dog. The two isolates were similar in terms of antibiogram, multilocus sequence typing (ST341), virulence genes, and only three SNPs were found to differentiate the two NTTB C. ulcerans isolates supporting a zoonotic transmission to or between the patient and his dog. Of interest, we found that the two C. ulcerans isolates, although not expressing the diphtheria toxin tox, possessed 13 out of 14 recently described virulence candidate genes. PMID- 26284491 TI - Synthesis of Optically Pure Spiro[cyclohexane-oxindoline] Derivatives via Catalytic Asymmetric Diels-Alder Reaction of Brassard-Type Diene with Methyleneindolines. AB - A highly efficient N,N'-dioxide-Zn(II) complex catalytic system for the asymmetric Diels-Alder reaction of Brassard-type diene with methyleneindolines was developed. The optically pure spiro[cyclohex[3]ene-1,3'-indoline]-1' carboxylate-2, 2'-dione derivatives containing three stereocenters were obtained in moderate yields with 98% to >99% ee in a stereospecific manner. PMID- 26284492 TI - Open channel block of NMDA receptors by diphenhydramine. AB - BACKGROUND AND PURPOSE: Diphenhydramine is a well known H1-receptor antagonist that plays a major role in clinical practice. Nowadays, diphenhydramine is primarily applied to prevent nausea but also its sedative and analgesic effects are of clinical importance. As other drugs mediating sedative and analgesic properties partly operate via the inhibition of glutamate receptors, we tested the hypothesis that diphenhydramine, as well interacts with excitatory ionotropic glutamate receptors. EXPERIMENTAL APPROACH: Electrophysiological patch-clamp experiments were performed on glutamate receptors which were heterologously expressed in human TsA cells. KEY RESULTS: Diphenhydramine inhibits NMDA-mediated membrane currents in a reversible and concentration-dependent manner at clinically relevant concentrations. The inhibition occurred in a noncompetitive manner. Diphenhydramine did not compete with NMDA or glycine for their binding sites and half-maximal inhibition was obtained around 25 MUM diphenhydramine, independent of the subunit composition. The inhibition was caused by a classical open channel blocking mechanism and varied strongly with the membrane potential. Our results suggest that diphenhydramine most probably interacts with the Mg2+ binding site or a very closely related area of the channel pore. CONCLUSION AND IMPLICATIONS: The data presented here provide evidence that the NMDA receptor antagonism of diphenhydramine contribute to its sedative and potentially LTP related effects like analgesia and amnesia. PMID- 26284493 TI - A DEVH-box RNA Helicase from Leishmania braziliensis is Associated to mRNA Cytoplasmic Granules. AB - RNA helicases are ubiquitous enzymes that participate in almost all aspects of RNA processing, including RNA and RNA-protein complex remodelling. In trypanosomatids, which post-transcriptionally regulate gene expression, the formation of different kinds of ribonucleoprotein granules under stress conditions modulates the parasite's RNA metabolism. This paper describes the isolation of a putative DEVH-box RNA helicase produced by promastigotes of Leishmania braziliensis. Using a Cy3-labelled dT30 oligo, FISH showed the localization of this protein to mRNA granules under starvation stress conditions. The central region of the protein was shown to be responsible for this behaviour. PMID- 26284495 TI - Insights into insulin-like peptide system in invertebrates from studies on IGF binding domain-containing proteins in the female mud crab, Scylla paramamosain. AB - Insulin-like peptides (ILPs) have been proved to exist extensively in invertebrates and play critical roles in regulating growth, metabolism and reproduction. ILP signaling system has been well defined in insects, with all key components homologous with vertebrate IGF signaling; however, counterparts of IGF binding proteins (IGFBPs) in vertebrates are not included in this system because of lacking sufficient researches in the related aspect. The present study firstly reports the identification of three kinds of invertebrate IGF binding (IB) domain containing protein genes from the mud crab Scylla paramamosain. Gene expression analysis suggested that they might be closely involved in ovarian development, but with separate roles. Subsequent bioinformatics analysis and in vitro experiments indicated that they are likely to serve as endogenous ILP-specific binding proteins in invertebrates. More importantly, based on the current evidence we inferred that in invertebrate, ILP system might take the place of IGF system in vertebrate species. PMID- 26284494 TI - Tumor suppression by MEG3 lncRNA in a human pituitary tumor derived cell line. AB - Human clinically non-functioning pituitary adenomas (NFAs) account for approximately 40% of diagnosed pituitary tumors. Epigenetic mutations in tumor suppressive genes play an important role in NFA development. Maternally expressed gene 3 (MEG3) is a long non-coding RNA (lncRNA) and we hypothesized that it is a candidate tumor suppressor whose epigenetic silencing is specifically linked to NFA development. In this study, we introduced MEG3 expression into PDFS cells, derived from a human NFA, using both inducible and constitutively active expression systems. MEG3 expression significantly suppressed xenograft tumor growth in vivo in nude mice. When induced in culture, MEG3 caused cell cycle arrest at the G1 phase. In addition, inactivation of p53 completely abolished tumor suppression by MEG3, indicating that MEG3 tumor suppression is mediated by p53. In conclusion, our data support the hypothesis that MEG3 is a lncRNA tumor suppressor in the pituitary and its inactivation contributes to NFA development. PMID- 26284496 TI - Effects of 17beta-estradiol on cardiac Na(+)/K(+)-ATPase in high fat diet fed rats. AB - The aim of this study was to investigate in vivo effects of estradiol on Na(+)/K(+)-ATPase activity/expression in high fat (HF) diet fed rats. Adult male Wistar rats were fed normally (Control, n = 7) or with a HF diet (Obese, n = 14) for 10 weeks. After 10 weeks, half of the obese rats were treated with estradiol (Obese + Estradiol, n = 7, 40 MUg/kg, i.p.) as a bolus injection and 24 h after treatment all the rats were sacrificed. Estradiol in vivo in obese rats in comparison with obese non-treated rats led to a statistically significant increase in concentration of serum Na(+) (p < 0.05), Na(+)/K(+)-ATPase activity (p < 0.01), expression of alpha1 (p < 0.01) and alpha2 (p < 0.05) subunit of Na(+)/K(+)-ATPase, both PI3K subunits p85 (p < 0.01), p110 (p < 0.05), and association of IRS-1 with p85 (p < 0.05), while significantly decrease expression of AT1 (p < 0.05) and Rho A (p < 0.01) proteins. Our results suggest that estradiol in vivo in pathophysiological conditions, such as obesity accompanied with insulin resistance stimulates activity and expression of Na(+)/K(+)-ATPase by a mechanism that involves the participation of IRS-1/PI3K/Akt signaling. In addition, the decreasing level of AT1 and Rho A proteins estradiol probably attenuates the detrimental effect of obesity to decreased IRS-1/PI3K association and consequently reduce Na(+)/K(+)-ATPase activity/expression. PMID- 26284497 TI - Perturbation biology nominates upstream-downstream drug combinations in RAF inhibitor resistant melanoma cells. AB - Resistance to targeted cancer therapies is an important clinical problem. The discovery of anti-resistance drug combinations is challenging as resistance can arise by diverse escape mechanisms. To address this challenge, we improved and applied the experimental-computational perturbation biology method. Using statistical inference, we build network models from high-throughput measurements of molecular and phenotypic responses to combinatorial targeted perturbations. The models are computationally executed to predict the effects of thousands of untested perturbations. In RAF-inhibitor resistant melanoma cells, we measured 143 proteomic/phenotypic entities under 89 perturbation conditions and predicted c-Myc as an effective therapeutic co-target with BRAF or MEK. Experiments using the BET bromodomain inhibitor JQ1 affecting the level of c-Myc protein and protein kinase inhibitors targeting the ERK pathway confirmed the prediction. In conclusion, we propose an anti-cancer strategy of co-targeting a specific upstream alteration and a general downstream point of vulnerability to prevent or overcome resistance to targeted drugs. PMID- 26284499 TI - Wedge Waveguides and Resonators for Quantum Plasmonics. AB - Plasmonic structures can provide deep-subwavelength electromagnetic fields that are useful for enhancing light-matter interactions. However, because these localized modes are also dissipative, structures that offer the best compromise between field confinement and loss have been sought. Metallic wedge waveguides were initially identified as an ideal candidate but have been largely abandoned because to date their experimental performance has been limited. We combine state of-the-art metallic wedges with integrated reflectors and precisely placed colloidal quantum dots (down to the single-emitter level) and demonstrate quantum plasmonic waveguides and resonators with performance approaching theoretical limits. By exploiting a nearly 10-fold improvement in wedge-plasmon propagation (19 MUm at a vacuum wavelength, lambdavac, of 630 nm), efficient reflectors (93%), and effective coupling (estimated to be >70%) to highly emissive (~90%) quantum dots, we obtain Ag plasmonic resonators at visible wavelengths with quality factors approaching 200 (3.3 nm line widths). As our structures offer modal volumes down to ~0.004lambdavac(3) in an exposed single-mode waveguide resonator geometry, they provide advantages over both traditional photonic microcavities and localized-plasmonic resonators for enhancing light-matter interactions. Our results confirm the promise of wedges for creating plasmonic devices and for studying coherent quantum-plasmonic effects such as long-distance plasmon-mediated entanglement and strong plasmon-matter coupling. PMID- 26284500 TI - Induced Gamma-Band Activity During Voluntary Movement: EEG Analysis for Clinical Purposes. AB - OBJECTIVE: Propose a simplified method applicable in routine clinical practice that uses EEG to assess induced gamma-band activity (GBA) in the 30-90 Hz frequency range in cerebral motor areas. DESIGN: EEG recordings (25 healthy subjects) of cerebral activity (at rest, motor task). GBA was obtained as power spectral density (PSD). GBA - defined as the gamma index (Igamma) - was calculated using the basal GBA (gammaB) and motor GBA (gammaMOV) PSD values. RESULTS: The mean values of Igamma were (IgammaR (right hand) = 1.30, IgammaL (left hand) = 1.22). Manual laterality showed a correlation with Igamma. CONCLUSIONS: Igamma may provide a useful way of indirectly assessing operation of activated motor neuronal circuits. It could be applied to diagnosis of motor area pathologies and as follow up in rehabilitation processes. Likewise, Igamma could enable the assessment of motor capacity, physical training and manual laterality in sport medicine. PMID- 26284501 TI - Formation of Klein Edge Doublets from Graphene Monolayers. AB - With increasing possibilities for applications of graphene, it is essential to fully characterize the rich topological variations in graphene edge structures. Using aberration-corrected transmission electron microscopy, dangling carbon doublets at the edge of monolayer graphene crystals have been observed. Unlike the single-atom Klein edge often found at zigzag edges, these carbon dimers were observed in various edge structure environments, but most frequently on the more stable armchair edges. Observation of this Klein edge doublet over time reveals that its existence enhances the stability of armchair edges and is a route to atom abstraction on zigzag edges. PMID- 26284498 TI - A molecular tweezer antagonizes seminal amyloids and HIV infection. AB - Semen is the main vector for HIV transmission and contains amyloid fibrils that enhance viral infection. Available microbicides that target viral components have proven largely ineffective in preventing sexual virus transmission. In this study, we establish that CLR01, a 'molecular tweezer' specific for lysine and arginine residues, inhibits the formation of infectivity-enhancing seminal amyloids and remodels preformed fibrils. Moreover, CLR01 abrogates semen-mediated enhancement of viral infection by preventing the formation of virion-amyloid complexes and by directly disrupting the membrane integrity of HIV and other enveloped viruses. We establish that CLR01 acts by binding to the target lysine and arginine residues rather than by a non-specific, colloidal mechanism. CLR01 counteracts both host factors that may be important for HIV transmission and the pathogen itself. These combined anti-amyloid and antiviral activities make CLR01 a promising topical microbicide for blocking infection by HIV and other sexually transmitted viruses. PMID- 26284502 TI - A Luminescent Cocaine Detection Platform Using a Split G-Quadruplex-Selective Iridium(III) Complex and a Three-Way DNA Junction Architecture. AB - In this study, a series of 10 in-house cyclometalated iridium(III) complexes bearing different auxiliary ligands were tested for their selectivity toward split G-quadruplex in order to construct a label-free switch-on cocaine detection platform employing a three-way junction architecture and a G-quadruplex motif as a signal output unit. Through two rounds of screening, we discovered that the iridium(III) complex 7 exhibited excellent selectivity toward the intermolecular G-quadruplex motif. A detection limit as low as 30 nM for cocaine can be achieved by this sensing approach with a linear relationship between luminescence intensity and cocaine concentration established from 30 to 300 nM. Furthermore, this sensing approach could detect cocaine in diluted oral fluid. We hope that our simple, signal-on, label-free oligonucleotide-based sensing method for cocaine using a three-way DNA junction architecture could act as a useful platform in bioanalytical research. PMID- 26284503 TI - Reaction-Based "Off-On" Fluorescent Probe Enabling Detection of Endogenous Labile Fe(2+) and Imaging of Zn(2+)-induced Fe(2+) Flux in Living Cells and Elevated Fe(2+) in Ischemic Stroke. AB - Fluorogenic sensors capable of spatiotemporally detecting Fe(2+) in biological systems are highly valuable in the study of iron biology. Toward this end, a new "off-on" Fe(2+)-selective fluorescent probe has been developed by incorporating an Fe(2+)-induced N-O cleavage of acylated hydroxylamine moiety into the naphthalimide fluorophore. The probe displays facile response (within 15 min) and good selectivity toward Fe(2+) with >27-fold enhancement of fluorescence intensity and high sensitivity of as low as 0.5 MUM with a noticeable 3-fold fluorescence enhancement. These features of the probe have been transformed into in the convenient detection of endogenous, basal level of labile Fe(2+) pools in living cells. Furthermore, we have demonstrated the capacity of the probe for the studies of important Fe(2+) related biological functions. It can respond to the Zn(2+)-induced Fe(2+) flux, an important event observed in stroke, and facilely detect the elevated level of Fe(2+) in the brain tissue of a rat undergoing ischemic stroke at the ischemic site. PMID- 26284504 TI - Addition to "Supramolecular Amphiphiles Based on Host-Guest Molecular Recognition Motifs". PMID- 26284505 TI - Foreign Body Aspiration of a Press-Through Package That Lodged between the Vocal Cords. PMID- 26284506 TI - Clinical Q & A: Translating Therapeutic Temperature Management from Theory to Practice. PMID- 26284507 TI - Structural conservation of prion strain specificities in recombinant prion protein fibrils in real-time quaking-induced conversion. AB - A major unsolved issue of prion biology is the existence of multiple strains with distinct phenotypes and this strain phenomenon is postulated to be associated with the conformational diversity of the abnormal prion protein (PrP(Sc)). Real time quaking-induced conversion (RT-QUIC) assay that uses Escherichia coli derived recombinant prion protein (rPrP) for the sensitive detection of PrP(Sc) results in the formation of rPrP-fibrils seeded with various strains. We demonstrated that there are differences in the secondary structures, especially in the beta-sheets, and conformational stability between 2 rPrP-fibrils seeded with either Chandler or 22L strains in the first round of RT-QUIC. In particular, the differences in conformational properties of these 2 rPrP-fibrils were common to those of the original PrP(Sc). However, the strain specificities of rPrP fibrils seen in the first round were lost in subsequent rounds. Instead, our findings suggest that nonspecific fibrils became the major species, probable owing to their selective growth advantage in the RT-QUIC. This study shows that at least some strain-specific conformational properties of the original PrP(Sc) can be transmitted to rPrP-fibrils in vitro, but further conservation appears to require unknown cofactors or environmental conditions or both. PMID- 26284508 TI - In vitro neutralization of prions with PrP(Sc)-specific antibodies. AB - Prion diseases reflect the misfolding of a self-protein (PrP(C)) into an infectious, pathological isomer (PrP(Sc)). By targeting epitopes uniquely exposed by misfolding, our group developed PrP(Sc)-specific vaccines to 3 disease specific epitopes (DSEs). Here, antibodies induced by individual DSE vaccines are evaluated for their capacity to neutralize prions in vitro. For both purified antibodies and immunoreactive sera, the PrP(Sc)-specific antibodies were equally effective in neutralizing prions. Further, there was no significant increase in neutralizing activity when multiple DSEs were targeted within an assay. At a low antibody concentration, the PrP(Sc)-specific antibodies matched the neutralization achieved by an antibody that may act via both PrP(C) and PrP(Sc). At higher doses, however, this pan-specific antibody was more effective, potentially due to a combined deactivation of PrP(Sc) and depletion of PrP(C). PMID- 26284509 TI - Cancer-associated fibroblasts in pancreatic adenocarcinoma. AB - Pancreatic ductal adenocarcinoma (PDAC) is one of the most highly malignant tumors with a very poor prognosis. In addition to the cancer cells, the stroma of tumor can expand by 50% and influence cancer cell growth. Cancer-associated fibroblasts (CAFs) are important components of tumor stroma. Cancer cells, normal fibroblasts, normal epithelial cells as well as bone marrow-derived myofibroblasts contribute to the emergence of CAFs through various cytokines (e.g., TGF-beta, SHH, PDGF) and epithelial-to-mesenchymal transition. CAFs affect cancer growth, survival, metastasis, angiogenesis and immunosurveillance through the secretion of various cytokines, such as CXCL12 and secreted protein acidic and rich in cystein. Also, CAFs correlate to the prognosis and chemoresistance of PDAC patients. As novel therapeutic targets, CAFs, and their relative factors, represent an important role in PDAC therapy. PMID- 26284510 TI - Rapid biosynthesis of silver nanoparticles using Crotalaria verrucosa leaves against the dengue vector Aedes aegypti: what happens around? An analysis of dragonfly predatory behaviour after exposure at ultra-low doses. AB - Aedes aegypti is a primary vector of dengue, a mosquito-borne viral disease infecting 50-100 million people every year. Here, we biosynthesised mosquitocidal silver nanoparticles (AgNP) using the aqueous leaf extract of Crotalaria verrucosa. The green synthesis of AgNP was studied by UV-vis spectroscopy, SEM, EDX and FTIR. C. verrucosa-synthesised AgNPs were toxic against A. aegypti larvae and pupae. LC50 of AgNP ranged from 3.496 ppm (I instar larvae) to 17.700 ppm (pupae). Furthermore, we evaluated the predatory efficiency of dragonfly nymphs, Brachydiplax sobrina, against II and III instar larvae of A. aegypti in an aquatic environment contaminated with ultra-low doses of AgNP. Under standard laboratory conditions, predation after 24 h was 87.5% (II) and 54.7% (III). In an AgNP-contaminated environment, predation was 91 and 75.5%, respectively. Overall, C. verrucosa-synthesised AgNP could be employed at ultra-low doses to reduce larval population of dengue vectors enhancing predation rates of dragonfly nymphs. PMID- 26284511 TI - Transcutaneous electrical nerve stimulation (TENS) for phantom pain and stump pain following amputation in adults. AB - BACKGROUND: This is the first update of a Cochrane review published in Issue 5, 2010 on transcutaneous electrical nerve stimulation (TENS) for phantom pain and stump pain following amputation in adults. Pain may present in a body part that has been amputated (phantom pain) or at the site of amputation (stump pain), or both. Phantom pain and stump pain are complex and multidimensional and the underlying pathophysiology remains unclear. The condition remains a severe burden for those who are affected by it. The mainstay treatments are predominately pharmacological, with increasing acknowledgement of the need for non-drug interventions. TENS has been recommended as a treatment option but there has been no systematic review of available evidence. Hence, the effectiveness of TENS for phantom pain and stump pain is currently unknown. OBJECTIVES: To assess the analgesic effectiveness of TENS for the treatment of phantom pain and stump pain following amputation in adults. SEARCH METHODS: For the original version of the review we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, AMED, CINAHL, PEDRO and SPORTDiscus (February 2010). For this update, we searched the same databases for relevant randomised controlled trials (RCTs) from 2010 to 25 March 2015. SELECTION CRITERIA: We only included RCTs investigating the use of TENS for the management of phantom pain and stump pain following an amputation in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We planned that where available and appropriate, data from outcome measures were to be pooled and presented as an overall estimate of the effectiveness of TENS. MAIN RESULTS: In the original review there were no RCTs that examined the effectiveness of TENS for the treatment of phantom pain and stump pain in adults. For this update, we did not identify any additional RCTs for inclusion. AUTHORS' CONCLUSIONS: There were no RCTs to judge the effectiveness of TENS for the management of phantom pain and stump pain. The published literature on TENS for phantom pain and stump pain lacks the methodological rigour and robust reporting needed to confidently assess its effectiveness. Further RCT evidence is required before an assessment can be made. Since publication of the original version of this review, we have found no new studies and our conclusions remain unchanged. PMID- 26284512 TI - Characteristics relating to the interiorization of acquired immunodeficiency syndrome in Brazil: a cross-sectional study. AB - BACKGROUND: In recent years there has been changes in the social and geographic profile of acquired immunodeficiency syndrome (AIDS). The aim of this study was to evaluate the internalization of AIDS in the state of Rondonia, Brazil. FINDINGS: In Rondonia, 1473 AIDS cases were reported, with an average annual incidence of 15.8/100,000 persons (42.7 % women). The most common mode of viral transmission was sexual (96.5 %), and the majority of the individuals had not completed their primary education (64.8 %). There was heterogeneity in relation to case distribution, involving almost all of the municipalities in the state. The average annual mortality rate was 2.5/100,000 persons. CONCLUSION: Rondonia has a higher incidence of AIDS than the national average and the northern region. Efforts to provide access to treatment and follow-up of these individuals should be implemented, prioritizing areas where the incidence is higher and decentralizing the treatment of patients with AIDS in the state. PMID- 26284513 TI - The Dynamics of Incomplete Lineage Sorting across the Ancient Adaptive Radiation of Neoavian Birds. AB - The diversification of neoavian birds is one of the most rapid adaptive radiations of extant organisms. Recent whole-genome sequence analyses have much improved the resolution of the neoavian radiation and suggest concurrence with the Cretaceous-Paleogene (K-Pg) boundary, yet the causes of the remaining genome level irresolvabilities appear unclear. Here we show that genome-level analyses of 2,118 retrotransposon presence/absence markers converge at a largely consistent Neoaves phylogeny and detect a highly differential temporal prevalence of incomplete lineage sorting (ILS), i.e., the persistence of ancestral genetic variation as polymorphisms during speciation events. We found that ILS-derived incongruences are spread over the genome and involve 35% and 34% of the analyzed loci on the autosomes and the Z chromosome, respectively. Surprisingly, Neoaves diversification comprises three adaptive radiations, an initial near-K-Pg super radiation with highly discordant phylogenetic signals from near-simultaneous speciation events, followed by two post-K-Pg radiations of core landbirds and core waterbirds with much less pronounced ILS. We provide evidence that, given the extreme level of up to 100% ILS per branch in super-radiations, particularly rapid speciation events may neither resemble a fully bifurcating tree nor are they resolvable as such. As a consequence, their complex demographic history is more accurately represented as local networks within a species tree. PMID- 26284514 TI - Creating a specialist protein resource network: a meeting report for the protein bioinformatics and community resources retreat. AB - During 11-12 August 2014, a Protein Bioinformatics and Community Resources Retreat was held at the Wellcome Trust Genome Campus in Hinxton, UK. This meeting brought together the principal investigators of several specialized protein resources (such as CAZy, TCDB and MEROPS) as well as those from protein databases from the large Bioinformatics centres (including UniProt and RefSeq). The retreat was divided into five sessions: (1) key challenges, (2) the databases represented, (3) best practices for maintenance and curation, (4) information flow to and from large data centers and (5) communication and funding. An important outcome of this meeting was the creation of a Specialist Protein Resource Network that we believe will improve coordination of the activities of its member resources. We invite further protein database resources to join the network and continue the dialogue. PMID- 26284515 TI - Effects of Grazing on Above- vs. Below-Ground Biomass Allocation of Alpine Grasslands on the Northern Tibetan Plateau. AB - Biomass allocation is an essential concept for understanding above- vs. below ground functions and for predicting the dynamics of community structure and ecosystem service under ongoing climate change. There is rare available knowledge of grazing effects on biomass allocation in multiple zonal alpine grassland types along climatic gradients across the Northern Tibetan Plateau. We collected the peak above- and below-ground biomass (AGB and BGB) values at 106 pairs of well matched grazed vs. fenced sites during summers of 2010-2013, of which 33 pairs were subject to meadow, 52 to steppe and 21 to desert-steppe. The aboveground net primary productivity (ANPP) was represented by the peak AGB while the belowground net primary productivity (BNPP) was estimated from ANPP, the ratio of living vs. dead BGB, and the root turnover rate. Two-ways analyses of variance (ANOVA) and paired samples comparisons with t-test were applied to examine the effects of pasture managements (PMS, i.e., grazed vs. fenced) and zonal grassland types on both ANPP and BNPP. Allometric and isometric allocation hypotheses were also tested between logarithmically transformed ANPP and BNPP using standardized major axis (SMA) analyses across grazed, fenced and overall sites. In our study, a high community-dependency was observed to support the allometric biomass allocation hypothesis, in association with decreased ANPP and a decreasing-to-increasing BNPP proportions with increasing aridity across the Northern Tibetan Plateau. Grazing vs. fencing seemed to have a trivial effect on ANPP compared to the overwhelming influence of different zonal grassland types. Vegetation links above and below-ground ecological functions through integrated meta-population adaptive strategies to the increasing severity of habitat conditions. Therefore, more detailed studies on functional diversity are essentially to achieve conservation and sustainability goals under ongoing climatic warming and intensifying human influences. PMID- 26284516 TI - Inhibition of Breast Cancer Cell Proliferation and In Vitro Tumorigenesis by a New Red Apple Cultivar. AB - PURPOSE: The aim of this study was to evaluate the antiproliferative activity in breast cancer cells and the inhibition of tumorigenesis in pre-neoplastic cells of a new apple cultivar with reddish pulp, called the Pelingo apple. METHODS: The antiproliferative activity was evaluated in MCF-7 and MDA-MB-231 human breast cancer cells. The inhibition of tumorigenesis was performed in JB6 promotion sensitive (P+) cells. RESULTS: Results showed that Pelingo apple juice is characterized by a very high polyphenol content and strongly inhibited breast cancer cell proliferation. Its antiproliferative activity was found to be higher than the other five apple juices tested. Pelingo juice induced cell accumulation in the G2/M phase of the cell cycle and autophagy through overexpression of p21, inhibition of extracellular signal-regulated kinases 1/2 (ERK1/2) activity and an increase in lipidated microtubule-associated protein-1 light chain-3 beta (LC3B). Remarkably, Pelingo juice inhibited the 12-o-tetra-decanoyl-phorbol-13-acetate (TPA)-induced tumorigenesis of JB6 P+ cells, suppressing colony formation in semi solid medium and TPA-induced ERK1/2 phosphorylation. CONCLUSIONS: Our data indicate that the Pelingo apple is rich in food components that can markedly inhibit in vitro tumorigenesis and growth of human breast cancer cells and could provide natural bioactive non-nutrient compounds, with potential chemopreventive activity. PMID- 26284517 TI - Autophagy Correlates with the Therapeutic Responsiveness of Malignant Pleural Mesothelioma in 3D Models. AB - Malignant pleural mesothelioma is a highly chemoresistant solid tumor. We have studied this apoptotic resistance using in vitro and ex vivo three-dimensional models, which acquire a high level of chemoresistance that can be reduced by PI3K/mTOR inhibitors. Here, we investigate the activity of GDC-0980, a novel dual PI3K/mTOR inhibitor, which has been proposed to be effective in mesothelioma. In this work, we aimed to identify mechanisms and markers of efficacy for GDC-0980 by utilizing 3D models of mesothelioma, both in vitro multicellular spheroids and ex vivo tumor fragment spheroids grown from patient tumor samples. We found that a subset of mesothelioma spheroids is sensitive to GDC-0980 alone and to its combination with chemotherapy. Unexpectedly, this sensitivity did not correlate with the activation of the Akt/mTOR pathway. Instead, sensitivity to GDC-0980 correlated with the presence of constitutive ATG13 puncta, a feature of autophagy, a cellular program that supports cells under stress. In tumor fragment spheroids grown from 21 tumors, we also found a subset (n = 11) that was sensitive to GDC-0980, a sensitivity that also correlated with the presence of ATG13 puncta. Interference with autophagy by siRNA of ATG7, an essential autophagic protein, increased the response to chemotherapy, but only in the sensitive multicellular spheroids. In the spheroids resistant to GDC-0980, autophagy appeared to play no role. In summary, we show that GDC-0980 is effective in mesothelioma 3D models that display ATG13 puncta, and that blockade of autophagy increases their response to chemotherapy. For the first time, we show a role for autophagy in the response to chemotherapy of 3D models of mesothelioma and propose ATG13 as a potential biomarker of the therapeutic responsiveness of mesothelioma. PMID- 26284518 TI - Obstructive Sleep Apnea Susceptibility Genes in Chinese Population: A Field Synopsis and Meta-Analysis of Genetic Association Studies. AB - BACKGROUND: Epidemiological studies to date have evaluated the association between genetic variants and the susceptibility to obstructive sleep apnea (OSA). However, the results of these studies have been inconclusive. In this current study we performed meta-analysis of genetic association studies (GAS) to pool OSA susceptible genes in Chinese population, to perform a more precise evaluation of the association. METHODS: Various databases (i.e., PubMed, EMBASE, HuGE Navigator, Wanfang and CNKI) were searched to identify all eligible GAS-related variants associated with susceptibility to OSA. The generalized odds ratio metric (ORG) and the odds ratio (OR) of the allele contrast were used to quantify the impact of genetic variants on the risk of OSA. Cumulative and recursive cumulative meta-analyses (CMA) were also performed to investigate the trend and stability of effect sizes as evidence was accumulated. RESULTS: Thirty-two GAS evaluating 13 polymorphisms in 10 genes were included in our meta-analysis. Significant associations were derived for four polymorphisms either for the allele contrast or for the ORG. The variants TNF-alpha-308G/A, 5-HTTLPR, 5 HTTVNTR, and APOE showed marginal significance for ORG (95% confidence interval [CI]): 2.01(1.31-3.07); 1.31(1.09-1.58); 1.85(1.16-2.95); 1.79(1.10-2.92); and 1.79(1.10-2.92) respectively. In addition, the TNF-alpha-308G/A, 5-HTTLPR, and 5 HTTVNTR variants showed significance for the allele contrast: 2.15(1.39-3.31); 2.26(1.58-3.24); 1.32(1.12-1.55); and 1.86(1.12-3.08) respectively. CMA showed a trend towards an association, and recursive CMA indicated that more evidence was needed to determine whether this was significant. CONCLUSIONS: TNF-alpha, 5-HTT, and APOE genes can all be proposed as OSA-susceptibility genes in Chinese population. Genome-wide association studies (GWAS) are therefore urgently needed to confirm our findings within a larger sample of OSA patients in China. PMID- 26284519 TI - Prevalence and Characterization of Carbapenem-Resistant Enterobacteriaceae Isolated from Mulago National Referral Hospital, Uganda. AB - INTRODUCTION: Carbapenemases have increasingly been reported in enterobacteriaceae worldwide. Most carbapenemases are plasmid encoded hence resistance can easily spread. Carbapenem-resistant enterobacteriaceae are reported to cause mortality in up to 50% of patients who acquire bloodstream infections. We set out to determine the burden of carbapenem resistance as well as establish genes encoding for carbapenemases in enterobacteriaceae clinical isolates obtained from Mulago National Referral Hospital, Uganda. METHODS: This was a cross-sectional study with a total of 196 clinical isolates previously collected from pus swabs, urine, blood, sputum, tracheal aspirates, cervical swabs, endomentrial aspirates, rectal swabs, Vaginal swabs, ear swabs, products of conception, wound biopsy and amniotic fluid. All isolates were subjected to phenotypic carbapenemase screening using Boronic acid-based inhibition, Modified Hodge and EDTA double combined disk test. In addition, all the isolates were subjected to PCR assay to confirm presence of carbapenemase encoding genes. RESULTS: The study found carbapenemase prevalence of 22.4% (44/196) in the isolates using phenotypic tests, with the genotypic prevalence slightly higher at 28.6% (56/196). Over all, the most prevalent gene was blaVIM (21,10.7%), followed by blaOXA-48 (19, 9.7%), blaIMP (12, 6.1%), blaKPC (10, 5.1%) and blaNDM-1 (5, 2.6%). Among 56 isolates positive for 67 carbapenemase encoding genes, Klebsiella pneumonia was the species with the highest number (52.2%). Most 32/67(47.7%) of these resistance genes were in bacteria isolated from pus swabs. CONCLUSION: There is a high prevalence of carbapenemases and carbapenem-resistance encoding genes among third generation cephalosporins resistant Enterobacteriaceae in Uganda, indicating a danger of limited treatment options in this setting in the near future. PMID- 26284521 TI - Sympathetic Tone Induced by High Acoustic Tempo Requires Fast Respiration. AB - Many studies have revealed the influences of music, and particularly its tempo, on the autonomic nervous system (ANS) and respiration patterns. Since there is the interaction between the ANS and the respiratory system, namely sympatho respiratory coupling, it is possible that the effect of musical tempo on the ANS is modulated by the respiratory system. Therefore, we investigated the effects of the relationship between musical tempo and respiratory rate on the ANS. Fifty-two healthy people aged 18-35 years participated in this study. Their respiratory rates were controlled by using a silent electronic metronome and they listened to simple drum sounds with a constant tempo. We varied the respiratory rate-acoustic tempo combination. The respiratory rate was controlled at 15 or 20 cycles per minute (CPM) and the acoustic tempo was 60 or 80 beats per minute (BPM) or the environment was silent. Electrocardiograms and an elastic chest band were used to measure the heart rate and respiratory rate, respectively. The mean heart rate and heart rate variability (HRV) were regarded as indices of ANS activity. We observed a significant increase in the mean heart rate and the low (0.04-0.15 Hz) to high (0.15-0.40 Hz) frequency ratio of HRV, only when the respiratory rate was controlled at 20 CPM and the acoustic tempo was 80 BPM. We suggest that the effect of acoustic tempo on the sympathetic tone is modulated by the respiratory system. PMID- 26284520 TI - A Subset of Cerebrospinal Fluid Proteins from a Multi-Analyte Panel Associated with Brain Atrophy, Disease Classification and Prediction in Alzheimer's Disease. AB - In this exploratory neuroimaging-proteomic study, we aimed to identify CSF proteins associated with AD and test their prognostic ability for disease classification and MCI to AD conversion prediction. Our study sample consisted of 295 subjects with CSF multi-analyte panel data and MRI at baseline downloaded from ADNI. Firstly, we tested the statistical effects of CSF proteins (n = 83) to measures of brain atrophy, CSF biomarkers, ApoE genotype and cognitive decline. We found that several proteins (primarily CgA and FABP) were related to either brain atrophy or CSF biomarkers. In relation to ApoE genotype, a unique biochemical profile characterised by low CSF levels of Apo E was evident in epsilon4 carriers compared to epsilon3 carriers. In an exploratory analysis, 3/83 proteins (SGOT, MCP-1, IL6r) were also found to be mildly associated with cognitive decline in MCI subjects over a 4-year period. Future studies are warranted to establish the validity of these proteins as prognostic factors for cognitive decline. For disease classification, a subset of proteins (n = 24) combined with MRI measurements and CSF biomarkers achieved an accuracy of 95.1% (Sensitivity 87.7%; Specificity 94.3%; AUC 0.95) and accurately detected 94.1% of MCI subjects progressing to AD at 12 months. The subset of proteins included FABP, CgA, MMP-2, and PPP as strong predictors in the model. Our findings suggest that the marker of panel of proteins identified here may be important candidates for improving the earlier detection of AD. Further targeted proteomic and longitudinal studies would be required to validate these findings with more generalisability. PMID- 26284522 TI - Effect of Common Genetic Variants of Growth Arrest-Specific 6 Gene on Insulin Resistance, Obesity and Type 2 Diabetes in an Asian Population. AB - OBJECTIVES: Growth arrest-specific 6 (Gas6), a vitamin K-dependent protein, has been implicated in systemic inflammation, obesity, and insulin resistance (IR). Data from recent studies suggest that polymorphisms in the Gas6 gene are associated with cardiovascular disorders and type 2 diabetes (T2D). However, the association of Gas6 gene variants with obesity, IR, and T2D development has not been explored. MATERIALS AND METHODS: Four common single nucleotide polymorphisms (SNPs) in the Gas6 gene were genotyped in 984 participants from the Stanford Asia Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) family cohort. An insulin suppression test was performed to determine IR based on steady-state plasma glucose (SSPG). Associations between IR indices and obesity, and SNP genotypes, based on previously-reported data for this cohort (Phase I), were analyzed. In the present follow-up study (Phase II), the effects of gene variants of Gas6 on the progression to T2D were explored in individuals who were free of T2D in Phase I. The mean follow-up period for Phase II was 5.7 years. RESULTS: The mean age of the study population in Phase I was 49.5 years and 16.7% of individuals developed T2D during follow-up. After adjusting for covariates, three SNPs (rs8191973, rs8197974, and rs7323932) were found to be associated with SSPG levels (p = 0.007, p = 0.03, and p = 0.011, respectively). This association remained significant after multiple testing and showed a significant interaction with physical activity for SNP rs8191973. However, no other significant correlations were observed between Gas6 polymorphisms and other indices of IR or obesity. A specific haplotype, AACG (from rs8191974, rs7323932, rs7331124, and rs8191973), was positively associated with SSPG levels (p = 0.0098). None of the polymorphisms were associated with an increased risk of T2D development. CONCLUSIONS: Our results suggest that Gas6 gene variants are associated with IR, although their effects on subsequent progression to T2D were minimal in this prospective Asian cohort. PMID- 26284524 TI - Correction: Exome Sequencing of Phenotypic Extremes Identifies CAV2 and TMC6 as Interacting Modifiers of Chronic Pseudomonas aeruginosa Infection in Cystic Fibrosis. PMID- 26284523 TI - Predictors of Individual Response to Placebo or Tadalafil 5mg among Men with Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: An Integrated Clinical Data Mining Analysis. AB - BACKGROUND: A significant percentage of patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) achieve clinically meaningful improvement when receiving placebo or tadalafil 5mg once daily. However, individual patient characteristics associated with treatment response are unknown. METHODS: This integrated clinical data mining analysis was designed to identify factors associated with a clinically meaningful response to placebo or tadalafil 5mg once daily in an individual patient with LUTS-BPH. Analyses were performed on pooled data from four randomized, placebo-controlled, double-blind, clinical studies, including about 1,500 patients, from which 107 baseline characteristics were selected and 8 response criteria. The split set evaluation method (1,000 repeats) was used to estimate prediction accuracy, with the database randomly split into training and test subsets. Logistic Regression (LR), Decision Tree (DT), Support Vector Machine (SVM) and Random Forest (RF) models were then generated on the training subset and used to predict response in the test subset. Prediction models were generated for placebo and tadalafil 5mg once daily Receiver Operating Curve (ROC) analysis was used to select optimal prediction models lying on the ROC surface. FINDINGS: International Prostate Symptom Score (IPSS) baseline group (mild/moderate vs. severe) for active treatment and placebo achieved the highest combined sensitivity and specificity of 70% and ~50% for all analyses, respectively. This was below the sensitivity and specificity threshold of 80% that would enable reliable allocation of an individual patient to either the responder or non-responder group. CONCLUSIONS: This extensive clinical data mining study in LUTS-BPH did not identify baseline clinical or demographic characteristics that were sufficiently predictive of an individual patient response to placebo or once daily tadalafil 5mg. However, the study reaffirms the efficacy of tadalalfil 5mg once daily in the treatment of LUTS-BPH in the majority of patients and the importance of evaluating individual patient need in selecting the most appropriate treatment. PMID- 26284525 TI - Hypertension in Sub-Saharan Africa: A Contextual View of Patterns of Disease, Best Management, and Systems Issues. AB - Sub-Saharan Africa (SSA) bears the highest burden of both communicable and noncommunicable disease and has the weakest health systems. Much attention is directed toward a rising burden of chronic disease in the setting of epidemiologic transition and urbanization. Indeed, the highest prevalence of hypertension globally is in the World Health Organization's African region at 46% of adults aged 25 and above. And while hypertension in SSA is common, its prevalence varies significantly between urban and rural settings. Although there is evidence for epidemiologic transition in urban areas, there is also evidence of static levels of hypertension within rural areas, which comprise more than 70% of the population of SSA. Furthermore, overall cardiovascular (CV) risk in rural areas remains low. The mean age of hypertensives in SSA is approximately 30s to 40s, burdening those at peak productivity. Complications of hypertension are frequent, given the poor levels of awareness and treatment (<10%) of hypertension on the continent. Such complications include primarily stroke and hypertensive heart disease, as ischemic heart disease is uncommon. Mortality associated with these complications is high, with in-hospital mortality from 2 different sites reported as around 20%. The overall burden of hypertension is likely to be more related to poor access and availability of health systems and is representative of a looming crisis in health care delivery. The best approaches to population wide treatment are those that utilize CV risk prediction for those with stage 1 hypertension, whereas treatment is generally indicated for all those with stage 2 or greater hypertension, especially in light of the high burden of stroke in SSA. Current guidelines recommend first-line drug therapy with a diuretic or calcium channel blocker. Despite these recommendations, the major obstacles to hypertension treatment are systemic and include the availability and cost of medications, the adequacy of health facilities and systems, and the lack of health insurance to address affordability. New and innovative systems-oriented approaches are needed to address the burden of hypertension on a platform of global equity. PMID- 26284526 TI - The Effect of National Cancer Screening on Disparity Reduction in Cancer Stage at Diagnosis by Income Level. AB - BACKGROUND: Early detection of cancer is an effective and efficient cancer management strategy. In South Korea, the National Health Insurance administers the National Cancer Screening Program to its beneficiaries. We examined the impact of the National Cancer Screening Program on socioeconomic disparities in cancer stage at diagnosis. METHODS: Cancer patients registered in the Korean Central Cancer Registry from January 1, 2010 to December 31, 2010 with a diagnosis of gastric cancer (n = 22,470), colon cancer (n = 16,323), breast cancer (n = 10,076), or uterine cervical cancer (n = 2,447) were included. Income level was divided into three groups according to their monthly contribution of National Health Insurance. We employed absolute (age-standardized prevalence rate, slope index of inequality) and relative (relative index of inequality) measures to separately examine social disparities among participants and non participants of the National Cancer Screening Program in terms of the early-stage rate. RESULTS: Age-standardized prevalence rates of early-stage by income group were always higher in participants than in non-participants. Furthermore, the age standardized prevalence rate of early-stage in the low income group of the participants was also higher than that of the high income group of the non participants. The sizes of disparities (both slope index of inequality and relative index of inequality) are smaller in participants compared to non participants. CONCLUSION: National Cancer Screening Program participation reduced income disparity in cancer stage at diagnosis. Population-based cancer screening programs can be used as an effective measure to reduce income disparity in cancer care. PMID- 26284527 TI - G-Quadruplex-Enabling Sequence within the Human Tyrosine Hydroxylase Promoter Differentially Regulates Transcription. AB - G-Quadruplexes (GQs) found within the promoter regions of genes are known to mostly act as repressors of transcription. Here we report a guanosine (G)-rich segment in the 3'-proximal promoter region of human tyrosine hydroxylase (TH), which acts as a necessary element for transcription. Tyrosine hydroxylase catalyzes the rate-limiting step in the catecholamine biosynthesis and is linked to several common neurological disorders such as Parkinson's and schizophrenia. A 45 nucleotide (nt) sequence (wtTH49) within the human TH promoter contains multiple G-stretches that are extremely well conserved among the primates but deviate in rodents, which raises the possibility of variation in the GQ structures formed in the two orders with the potential for a distinctive functional outcome. Biochemical and biophysical studies, including single molecule Forster resonance energy transfer, indicate that the wtTH49 sequence can adopt multiple GQ structures by using different combinations of G-stretches. A functional assay performed with 2.8 kb of the 3'-proximal end of the TH promoter and a mutated version (TH49fm; mutated wtTH49) that is unable to form any GQ structure indicates that overall the GQ-enabling wtTH49 sequence is functionally necessary and enhances human TH promoter activity by 5-fold compared to that of the mutant. Two additional mutants, each of which was designed to form distinct GQs, differentially affected reporter gene transcription. A cationic porphyrin TMPyP4 destabilizes the wtTH49 GQ and lowers the level of reporter gene expression, although its analogue, TMPyP2, fails to elicit any response. The 45 nt G-rich sequence within the human TH promoter can form multiple GQ structures, is a necessary element in transcription, and depending on the utilized combination of G-stretches affects transcription in different ways. PMID- 26284528 TI - Severe Infections in HIV-Exposed Uninfected Infants Born in a European Country. AB - BACKGROUND: Several studies indicate that HIV-exposed uninfected (HEU) children have a high infectious morbidity. We previously reported an increased incidence of group B streptococcus (GBS) infections in HEU infants born in Belgium. METHODS: This study was undertaken to evaluate the incidence and risk factors of all cause severe infections in HEU infants born in Belgium between 1985 and 2006, including the pre-antiretroviral (ARV) prophylaxis era (1985 to 1994). The medical charts of 537 HEU infants followed in a single center were reviewed. RESULTS: The incidence rate of severe infections during the first year of life was 16.8/100 HEU infant-years. The rates of invasive S. pneumoniae (0.62/100 infant-years) and GBS infections (1.05/100 infant-years) were, respectively, 4 and 13-fold higher in HEU infants than in the general infant population. Preterm birth was a risk factor for severe infections in the neonatal period (aOR = 21.34, 95%CI:7.12-63.93) and post-neonatal period (aHR = 3.00, 95%CI:1.53-5.88). As compared to the pre-ARV prophylaxis era, infants born in the ARV prophylaxis era (i.e., after April 1994) had a greater risk of severe infections (aHR = 2.93; 95%CI:1.07-8.05). This risk excess was present in those who received ARV prophylaxis (aHR 2.01, 95%CI 0.72-5.65) and also in those born in the ARV prophylaxis era who did not benefit from ARV prophylaxis as a result of poor access to antenatal care or lack of compliance (aHR 3.06, 95%CI 0.88-10.66). CONCLUSIONS: In HEU infants born in an industrialized country, preterm birth and being born during the ARV prophylaxis era were risk factors of severe infections throughout the first year of life. These observations have important implications for the clinical management of HIV-infected mothers and their infants. PMID- 26284529 TI - The Involvement of Oxytocin in the Subthalamic Nucleus on Relapse to Methamphetamine-Seeking Behaviour. AB - The psychostimulant methamphetamine (METH) is an addictive drug of abuse. The neuropeptide oxytocin has been shown to modulate METH-related reward and METH seeking behaviour. Recent findings implicated the subthalamic nucleus (STh) as a key brain region in oxytocin modulation of METH-induced reward. However, it is unclear if oxytocin acts in this region to attenuate relapse to METH-seeking behaviour, and if this action is through the oxytocin receptor. We aimed to determine whether oxytocin pretreatment administered into the STh would reduce reinstatement to METH use in rats experienced at METH self-administration, and if this could be reversed by the co-administration of the oxytocin receptor antagonist desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT. Male Sprague Dawley rats underwent surgery to implant an intravenous jugular vein catheter and bilateral microinjection cannulae into the STh under isoflourane anaesthesia. Rats were then trained to self-administer intravenous METH (0.1 mg/kg/infusion) by lever press during 2-hour sessions under a fixed ratio 1 schedule for 20 days. Following extinction of lever press activity, the effect of microinjecting saline, oxytocin (0.2 pmol, 0.6 pmol, 1.8 pmol, 3.6 pmol) or co-administration of oxytocin (3.6 pmol) and desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT (3 nmol) into the STh (200 nl/side) was examined on METH-primed reinstatement (1 mg/kg; i.p.). We found that local administration of the highest oxytocin dose (3.6 pmol) into the STh decreased METH-induced reinstatement and desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT had a non-specific effect on lever press activity. These findings highlight that oxytocin modulation of the STh is an important modulator of relapse to METH abuse. PMID- 26284530 TI - Using a Multitest Algorithm to Improve the Positive Predictive Value of Rapid HIV Testing and Linkage to HIV Care in Nonclinical HIV Test Sites. AB - BACKGROUND: Use of a rapid HIV testing algorithm (RTA) in which all tests are conducted within one client appointment could eliminate off-site confirmatory testing and reduce the number of persons not receiving confirmed results. METHODS: An RTA was implemented in 9 sites in Los Angeles and San Francisco; results of testing at these sites were compared with 23 sites conducting rapid HIV testing with off-site confirmation. RTA clients with reactive results on more than 1 rapid test were considered HIV+ and immediately referred for HIV care. The positive predictive values (PPVs) of a single rapid HIV test and the RTA were calculated compared with laboratory-based confirmatory testing. A Poisson risk regression model was used to assess the effect of RTA on the proportion of HIV+ persons linked to HIV care within 90 days of a reactive rapid test. RESULTS: The PPV of the RTA was 100% compared with 86.4% for a single rapid test. The time between testing and receipt of RTA results was on average 8 days shorter than laboratory-based confirmatory testing. For risk groups other than men who had sex with men, the RTA increased the probability of being in care within 90 days compared with standard testing practice. CONCLUSIONS: The RTA increased the PPV of rapid testing to 100%, giving providers, clients, and HIV counselors timely information about a client's HIV-positive serostatus. Use of RTA could reduce loss to follow-up between testing positive and confirmation and increase the proportion of HIV-infected persons receiving HIV care. PMID- 26284532 TI - Kinetics of CO/CO2 and H2/H2O reactions at Ni-based and ceria-based solid-oxide cell electrodes. AB - The solid oxide electrochemical cell (SOC) is an energy conversion technology that can be operated reversibly, to efficiently convert chemical fuels to electricity (fuel cell mode) as well as to store electricity as chemical fuels (electrolysis mode). The SOC fuel-electrode carries out the electrochemical reactions CO2 + 2e(-) <-> CO + O(2-) and H2O + 2e(-) <-> H2 + O(2-), for which the electrocatalytic activities of different electrodes differ considerably. The relative activities in CO/CO2 and H2/H2O and the nature of the differences are not well studied, even for the most common fuel-electrode material, a composite of nickel and yttria/scandia stabilized zirconia (Ni-SZ). Ni-SZ is known to be more active for H2/H2O than for CO/CO2 reactions, but the reported relative activity varies widely. Here we compare AC impedance and DC current-overpotential data measured in the two gas environments for several different electrodes comprised of Ni-SZ, Gd-doped CeO2 (CGO), and CGO nanoparticles coating Nb-doped SrTiO3 backbones (CGOn/STN). 2D model and 3D porous electrode geometries are employed to investigate the influence of microstructure, gas diffusion and impurities.Comparing model and porous Ni-SZ electrodes, the ratio of electrode polarization resistance in CO/CO2vs. H2/H2O decreases from 33 to 2. Experiments and modelling suggest that the ratio decreases due to a lower concentration of impurities blocking the three phase boundary and due to the nature of the reaction zone extension into the porous electrode thickness. Besides showing higher activity for H2/H2O reactions than CO/CO2 reactions, the Ni/SZ interface is more active for oxidation than reduction. On the other hand, we find the opposite behaviour in both cases for CGOn/STN model electrodes, reporting for the first time a higher electrocatalytic activity of CGO nanoparticles for CO/CO2 than for H2/H2O reactions in the absence of gas diffusion limitations. We propose that enhanced surface reduction at the CGOn/gas two phase boundary in CO/CO2 and in cathodic polarization can explain why the highest reaction rate is obtained for CO2 electrolysis. Large differences observed between model electrode kinetics and porous electrode kinetics are discussed. PMID- 26284531 TI - Gender-Related Risk Factors Improve Mortality Predictive Ability of VACS Index Among HIV-Infected Women. AB - BACKGROUND: Adding gender-related modifiable characteristics or behaviors to the Veterans Aging Cohort Study (VACS) index might improve the accuracy of predicting mortality among HIV-infected women on treatment. We evaluated the VACS index in women with HIV, determined whether additional variables would improve mortality prediction, and quantified the potential for improved survival associated with reduction in these additional risk factors. METHODS: The VACS index (based on age, CD4 count, HIV-1 RNA, hemoglobin, aspartate aminotransferase, alanine aminotransferase, platelets, creatinine, and Hepatitis C status) was validated in HIV-infected women in the Women's Interagency HIV Study (WIHS) who initiated antiretroviral therapy between January 1996 and December 2007. Models were constructed adding race, depression, abuse, smoking, substance use, transactional sex, and comorbidities to determine whether predictability improved. Population attributable fractions were calculated. RESULTS: The VACS index accurately predicted 5-year mortality in 1057 WIHS women with 1 year on highly active antiretroviral therapy with c-index 0.83 [95% confidence interval (CI): 0.79 to 0.87]. In multivariate analysis, the VACS index score [adjusted hazard ratio (aHR) for a 5-point increment 1.30; 95% CI: 1.25 to 1.35], depressive symptoms (aHR 1.73; 95% CI: 1.17 to 2.56), and history of transactional sex (aHR 1.93; 95% CI: 1.33 to 1.82) were independent statistically significant predictors of mortality. CONCLUSIONS: Both depression and transactional sex significantly improved the performance of the VACS index in predicting mortality among HIV infected women. Providing treatment for depression and addressing economic and psychosocial instability in HIV-infected women would improve health and perhaps point to a broader public health approach to reducing HIV mortality. PMID- 26284533 TI - Awareness of Stroke Risk after TIA in Swiss General Practitioners and Hospital Physicians. AB - BACKGROUND: Transient ischemic attacks (TIA) are stroke warning signs and emergency situations, and, if immediately investigated, doctors can intervene to prevent strokes. Nevertheless, many patients delay going to the doctor, and doctors might delay urgently needed investigations and preventative treatments. We set out to determine how much general practitioners (GPs) and hospital physicians (HPs) knew about stroke risk after TIA, and to measure their referral rates. METHODS: We used a structured questionnaire to ask GPs and HPs in the catchment area of the University Hospital of Bern to estimate a patient's risk of stroke after TIA. We also assessed their referral behavior. We then statistically analysed their reasons for deciding not to immediately refer patients. RESULTS: Of the 1545 physicians, 40% (614) returned the survey. Of these, 75% (457) overestimated stroke risk within 24 hours, and 40% (245) overestimated risk within 3 months after TIA. Only 9% (53) underestimated stroke risk within 24 hours and 26% (158) underestimated risk within 3 months; 78% (473) of physicians overestimated the amount that carotid endarterectomy reduces stroke risk; 93% (543) would rigorously investigate the cause of a TIA, but only 38% (229) would refer TIA patients for urgent investigations "very often". Physicians most commonly gave these reasons for not making emergency referrals: patient's advanced age; patient's preference; patient was multimorbid; and, patient needed long-term care. CONCLUSIONS: Although physicians overestimate stroke risk after TIA, their rate of emergency referral is modest, mainly because they tend not to refer multimorbid and elderly patients at the appropriate rate. Since old and frail patients benefit from urgent investigations and treatment after TIA as much as younger patients, future educational campaigns should focus on the importance of emergency evaluations for all TIA patients. PMID- 26284535 TI - Ultrathin Black Phosphorus Nanosheets for Efficient Singlet Oxygen Generation. AB - Benefiting from its strong oxidizing properties, the singlet oxygen has garnered serious attentions in physical, chemical, as well as biological studies. However, the photosensitizers for the generation of singlet oxygen bear in low quantum yields, lack of long wavelength absorption band, poor biocompatibility, undegradable in living tissues, and so on. Here we first demonstrate the exfoliated black phosphorus nanosheets to be effective photosensitizers for the generation of singlet oxygen with a high quantum yield of about 0.91, rendering their attractive applications in catalysis and photodynamic therapy. Through in vitro and in vivo studies, the water dispersible black phosphorus nanosheets show notable cancer therapy ability. In addition, the photodegradable character of black phosphorus from element to biocompatible phosphorus oxides further highlights its therapeutic potential against cancer. This study will not only expand the breadth of study in black phosphorus but also offer an efficient catalyst and photodynamic therapy agent. PMID- 26284534 TI - The Interaction of FABP with Kapalpha. AB - Gene-activating lipophilic compounds are carried into the nucleus when loaded on fatty-acid-binding proteins (FABP). Some of these proteins are recognized by the alpha-Karyopherin (Kapalpha) through its nuclear localization signal (NLS) consisting of three positive residues that are not in a continuous sequence. The Importin system can distinguish between FABP loaded with activating and non activating compounds. In the present study, we introduced molecular dynamics as a tool for clarifying the mechanism by which FABP4, loaded with activating ligand (linoleate) is recognized by Kapalpha. In the first phase, we simulated the complex between KapalphaDeltaIBB (termed "Armadillo") that was crystallized with two NLS hepta-peptides. The trajectory revealed that the crystal-structure orientation of the peptides is rapidly lost and new interactions dominate. Though, the NLS sequence of FABP4 is cryptic, since the functional residues are not in direct sequence, implicating more than one possible conformation. Therefore, four possible docked conformations were generated, in which the NLS of FABP4 is interacting with either the major or the minor sites of Kapalpha, and the N -> C vectors are parallel or anti-parallel. Out of these four basic starting positions, only the FABP4-minor site complex exhibited a large number of contact points. In this complex, the FABP interacts with the minor and the major sites, suppressing the self-inhibitory interaction of the Kapalpha, rendering it free to react with Kapbeta. Finally, we propose that the transportable conformation generated an extended hydrophobic domain which expanded out of the boundary of the FABP4, allowing the loaded linoleate to partially migrate out of the FABP into a joint complex in which the Kapalpha contributes part of a combined binding pocket. PMID- 26284536 TI - Predictors and Diagnostic Strategies for Early-Stage Pancreatic Ductal Adenocarcinoma: A Retrospective Study. AB - OBJECTIVES: As a strategy to diagnose early-stage pancreatic ductal adenocarcinoma (PDAC) is urgently needed, we aimed to clarify characteristics of early-stage PDAC. METHODS: We retrospectively reviewed medical records of 299 consecutive patients who underwent R0 or R1 surgical resection for PDAC between 1994 and 2013 and compared clinical characteristics between patients with early stage (stages 0-I by Japanese General Rules for Pancreatic Cancer) and advanced stage (stages II-IV) disease. Diagnostic processes were also analyzed. RESULTS: Twenty-four patients (8%) had early-stage PDAC (stage 0: 11; stage I: 13). Univariate and multivariate analyses showed that presence or history of intraductal papillary mucinous neoplasm (P < 0.01), history of pancreatitis (P < 0.01), and presence or history of extrapancreatic malignancies (P = 0.01) independently predicted detection of early-stage PDAC. Cytological examination during endoscopic retrograde pancreatography cytology was ~65% sensitive in preoperative diagnosis of early-stage PDAC, whereas other imaging modalities were only 29% to 38% sensitive; 9 of 24 early-stage PDACs were diagnosed by endoscopic retrograde pancreatography cytology alone. CONCLUSIONS: Endoscopic retrograde pancreatography cytology for patients with intraductal papillary mucinous neoplasm or pancreatitis may help diagnose early-stage PDAC. Surveillance of extrapancreatic malignancies might also provide opportunities to detect early stage PDAC as a second malignancy. PMID- 26284537 TI - Quercetin Mediates beta-Catenin in Pancreatic Cancer Stem-Like Cells. AB - OBJECTIVE: The aim of this study is to explore how quercetin interacts with pancreatic cancer stem-like cells and the mechanism underlying the effective quercetin-mediated suppression. METHODS: A model of pancreatic cancer stem-like cells was generated by using a sphere formation culture system. A comparative analysis was performed between the parent cells and pancreatic cancer stem-like cells with a related treatment strategy focusing on cancer stem cell (CSC) properties and drug-resistance-related mechanisms in vitro. RESULTS: Our data show that pancreatic cancer stem-like cells have greater resistance to gemcitabine and stronger CSC properties compared with the parent cells. In contrast to the pancreatic cancer stem-like cells, overexpression of beta-catenin was observed in the parent cells. Quercetin suppressed proliferation, invasion and self-renewal capacity, and CSC surface markers expression, with alterations of beta-catenin in pancreatic cancer stem-like cells. The combination of quercetin and gemcitabine can reduce tumor growth and decrease drug resistance in pancreatic cancer. CONCLUSIONS: beta-Catenin plays an important role in maintenance and progression of pancreatic cancer. Targeting beta-catenin using quercetin combined with gemcitabine may be a treatment strategy to improve prognosis in patients with pancreatic cancer. PMID- 26284538 TI - Synthesis and Divergent Electronic Properties of Two Ring-Fused Derivatives of 9,10-Diphenylanthracene. AB - Two new contorted polycyclic aromatic hydrocarbons (PAHs) 1 and 2 were synthesized by acid-catalyzed benzannulation of a substituted anthracene. The isomers reveal dissimilar photophysical and redox properties with 2 having a much smaller HOMO-LUMO gap than 1. In the solid state, 2 packs in a unique two dimensional herringbone motif that gives rise to efficient ambipolar charge transport in OFET devices, a feature not previously observed in contorted PAHs. On the other hand, 1 packs in one-dimensional dimerized pi-stacks and displays insulating properties. PMID- 26284539 TI - Durability of Response in Children Treated With Pegylated Interferon alfa [corrected] 2a +/- Ribavirin for Chronic Hepatitis C. AB - OBJECTIVES: No long-term data have been published on the durability of response following pegylated interferon (PegIFN) treatment in children with chronic hepatitis C. This prospective, multicenter, long-term follow-up (LTFU) study aimed to assess long-term durability of sustained virological response (SVR), long-term safety and tolerability, and the association between IL28B genotype and treatment response, in children previously treated with PegIFN alfa-2a +/- ribavirin (RBV) in the PEDS-C trial. METHODS: A total of 93 patients were assessed for enrollment, and 38 enrolled in the study. Patients attended 2 study visits: 5 (mean 5.6, range 4.1-6.6) and 6 (6.6, 5.1-7.7) years after treatment cessation. Standardized medical history, physical examination, and laboratory testing were performed at these visits. Reminder telephone calls were conducted at 4 and 8 months after the initial visit. RESULTS: The LTFU cohort was the representative of the original PEDS-C cohort because both baseline and treatment characteristics were comparable. Of the 38 participants, 21 achieved SVR (responders) during the PEDS-C trial and 17 had not (nonresponders). All 21 responders maintained undetectable hepatitis C virus RNA during the LTFU (4.4-7.0 years after achieving SVR) in contrast to the nonresponders who demonstrated persistent viremia. IL28B CC genotype was associated with SVR (67% vs 30% in non CC, P = 0.028). CONCLUSION: Long-term durability of SVR is excellent following PegIFN alfa-2a treatment in children with chronic hepatitis C; SVR is higher in those with IL28B CC versus non-CC. PMID- 26284540 TI - Solitary Hepatic Nodule Adjacent to the Right Portal Vein: A Common Finding of Alagille Syndrome? AB - BACKGROUND: Hepatic lesions have been described in Alagille syndrome (ALGS) in isolated case reports, and most of these have been reported to be hepatocellular carcinoma. OBJECTIVES: The aim of the present study was to determine the frequency, imaging, and histopathologic characteristics of hepatic lesions in children with ALGS. METHODS: Available abdominal imaging of children with ALGS was retrospectively reviewed to note the presence of any focal liver lesion, its location, and imaging characteristics. Other findings including signs of portal hypertension, portal lymph nodes, and splenic and renal abnormalities were also noted. Findings were correlated with pathology in available cases and with clinical follow-up. RESULTS: Of 55 children with clinically and/or genetically confirmed ALGS followed in the liver clinic, 39 (19 boys, 20 girls; mean age 8.9 years) with imaging available on picture archival and communication system were included in the study. Focal hepatic lesions were seen in 12 of the 39 (30%) children, solitary in 11 and multiple in 1. Ten of these children had a large nodule adjacent to the right portal vein. The median diameter of the lesions was 8.1 cm (range 5.6-9.8 cm). Magnetic resonance imaging features and pathology in available cases were suggestive of a regenerative nodule. alpha-fetoprotein levels were normal in all except 1 child who had mild elevation. CONCLUSIONS: Combining our series and previous case reports, the presence of a large nodule adjacent to the right portal vein appears to be a common finding in ALGS. The typical location, normal alpha-fetoprotein levels, and magnetic resonance imaging features with vessels coursing through the lesion can reliably differentiate this benign nodule from hepatocellular carcinoma. PMID- 26284541 TI - Do Distinct Functional Dyspepsia Subtypes Exist in Children? AB - BACKGROUND AND AIM: Two different subtypes of functional dyspepsia (FD) are recognized in adults: epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS). The aim of the study was to assess the presence of FD subtypes in childhood at diagnosis and to observe changes at follow-up. METHODS: A total of 100 patients with a diagnosis of FD based on pediatric Rome III criteria were consecutively enrolled. FD subtypes were successively classified through adult Rome III classification. Children were revaluated after 6 months of follow-up (T1). RESULTS: At T0, 17 (17%) of 100 patients were classified as EPS, whereas 47 (47%) of 100 patients fulfilled criteria for PDS. In 36 (36%) of 100 children an overlap between the 2 subtypes was identified. Nausea was significantly higher in PDS and overlap groups when compared with EPS (chi = 21.7, P = 0.0001; chi = 20.7, P = 0.0001). Headache was significantly increased in PDS and overlap groups compared with patients with EPS (chi = 9.8, P = 0.001; chi = 13.1, P = 0.0001, respectively). At T1 among children belonging to PDS group at enrolment, 9 of 47 (19.1%) changed to EPS group, and 9 of 47 (19.1%) changed to the overlap group. Five (29.4%) of 17 patients and 2 (11.8%) of 17 children diagnosed as having EPS at T0 switched to PDS and overlap group, respectively. Of the 36 patients with overlap at enrollment, 11 (30.6%) satisfied criteria for PDS, and 7 (19.4%) switched to EPS group. CONCLUSIONS: Two distinct FD subtypes are identifiable in pediatric population. A high percentage of overlap and a variation of subtype over time were found, suggesting a common pathophysiologic mechanism. PMID- 26284542 TI - Practice Variations in the Management of Inflammatory Bowel Disease Between Pediatric and Adult Gastroenterologists. AB - BACKGROUND: Different practice guidelines and consensus statements for both pediatric- and adult-onset inflammatory bowel disease exist. Although variations in medical care among gastroenterologists are common, it is unknown whether there are fundamental differences between disciplines. The primary aim of the present study was to investigate differences in common practices across disciplines. METHODS: This was a prospective, questionnaire-based survey of gastroenterologists attending gastroenterology meetings in Israel. The questionnaire covered attitudes to medical resources, diagnostic and follow-up measures as well as therapeutic approaches. RESULTS: Overall, 120 (60%) of the approached adult gastroenterologists (AGs) and 49 (75%) pediatric gastroenterologists (PGs) completed the questionnaire. The 2 groups differed significantly in various practice areas. Pediatric patients are seen more frequently and for longer appointments. PGs tend to assess thiopurine metabolites (96% vs 47%) more often during treatment. There is a significant variation in practice between groups concerning infectious serology status and vaccinations. Methotrexate in Crohn patients is used more commonly by PGs (55% vs 22%). Long term combination therapy of thiopurines and anti-tumor necrosis factoralpha agents is used more often by AGs. In patients with ulcerative colitis AGs use oral 5-aminosalicylic acid once daily (51% vs 21%) and add rectal agents from the first day of treatment (72% vs 35%) more often as compared with PGs. CONCLUSIONS: This study demonstrates that common practices in inflammatory bowel disease patients differ significantly between adult and pediatric practitioners. These findings call for investigating the reasons for these differences and promoting strategies to diminish these gaps. PMID- 26284543 TI - VEGF Receptor-2-Linked PI3K/Calpain/SIRT1 Activation Mediates Retinal Arteriolar Dilations to VEGF and Shear Stress. AB - PURPOSE: Vasomotor responses of retinal arterioles to luminal flow/shear stress and VEGF have a critical role in governing retinal blood flow possibly via nitric oxide synthase (NOS) activation. However, the cellular mechanism for flow sensitive vasomotor activity in relation to VEGF signaling in retinal arterioles has not been characterized. We used an isolated vessel approach to specifically address this issue. METHODS: Porcine retinal arterioles were isolated, cannulated, and pressurized to 55 cm H2O luminal pressure by two independent reservoir systems. Luminal flow was increased stepwise by creating hydrostatic pressure gradients across two reservoirs. Diameter changes and associated signaling mechanisms corresponding to increased flow and VEGF receptor 2 (VEGFR2) activation were assessed using videomicroscopic, pharmacological, and molecular tools. RESULTS: Retinal arterioles developed basal tone under zero-flow condition and dilated concentration-dependently to VEGF165. Stepwise increases in flow produced graded vasodilation. Vasodilations to VEGF165 and increased flow were abolished by endothelial removal, and inhibited by pharmacological blockade of VEGFR2, NOS, phosphoinositide 3-kinase (PI3K), calpains, or sirtuin-1 (SIRT1) deacetylase. A VEGF165 antibody blocked vasodilation to VEGF165 but not flow. Immunostaining indicated that VEGFR2 was expressed in the endothelial and smooth muscle layers of retinal arterioles. CONCLUSIONS: Ligand-dependent and ligand independent activation of VEGFR2 in the endothelium mediates NO-dependent dilations of porcine retinal arterioles in response to VEGF165 and luminal flow/shear stress, respectively. It appears that NOS stimulation via PI3K, calpain proteases, and SIRT1-dependent deacetylation downstream from VEGFR2 activation contributes to these vasodilator responses. PMID- 26284545 TI - Imaging of the Corneal Subbasal Whorl-like Nerve Plexus: More Accurate Depiction of the Extent of Corneal Nerve Damage in Patients With Diabetes. AB - PURPOSE: To show that noninvasive in vivo corneal confocal microscopy (IVCM) can make more accurate imaging of the corneal subbasal nerve plexus possible. This diagnostic technique monitors the status of diabetic peripheral neuropathy. However, it is difficult to accurately confirm the corneal area captured by IVCM, which can induce measurement errors. Because the whorl-like characteristic pattern of the corneal subbasal nerve plexus is in the inferocentral cornea, we evaluated whether IVCM images of the whorl-like patterns can accurately evaluate the corneal nerve fibers in diabetic neuropathy. METHODS: Forty-seven patients with diabetes (DM group) and 21 healthy control subjects underwent IVCM examination to compare the characteristics of the corneal subbasal nerve plexus around the central cornea (conventional method) and the whorl-like pattern in the inferocentral cornea (study method). We measured the total corneal nerve fiber and branch length (CNFL). RESULTS: The total CNFL were significantly shorter in the DM group than in the control group and tended to decrease with progression of diabetic retinopathy, nephropathy, neuropathy, and decreased corneal sensation. There was a significant positive correlation between the CNFL values obtained with the conventional method and those obtained with the study method. The coefficient of variation of the CNFL values in the study method was significantly smaller than in the conventional method. CONCLUSIONS: Our findings indicated that IVCM measurements of the whorl-like patterns may accurately define the extent of corneal nerve damage in order to monitor diabetic peripheral neuropathy. PMID- 26284544 TI - Visual Cone Arrestin 4 Contributes to Visual Function and Cone Health. AB - PURPOSE: Visual arrestins (ARR) play a critical role in shutoff of rod and cone phototransduction. When electrophysiological responses are measured for a single mouse cone photoreceptor, ARR1 expression can substitute for ARR4 in cone pigment desensitization; however, each arrestin may also contribute its own, unique role to modulate other cellular functions. METHODS: A combination of ERG, optokinetic tracking, immunohistochemistry, and immunoblot analysis was used to investigate the retinal phenotypes of Arr4 null mice (Arr4-/-) compared with age-matched control, wild-type mice. RESULTS: When 2-month-old Arr4-/- mice were compared with wild-type mice, they had diminished visual acuity and contrast sensitivity, yet enhanced ERG flicker response and higher photopic ERG b-wave amplitudes. In contrast, in older Arr4-/- mice, all ERG amplitudes were significantly reduced in magnitude compared with age-matched controls. Furthermore, in older Arr4-/- mice, the total cone numbers decreased and cone opsin protein immunoreactive expression levels were significantly reduced, while overall photoreceptor outer nuclear layer thickness was unchanged. CONCLUSIONS: Our study demonstrates that Arr4-/- mice display distinct phenotypic differences when compared to controls, suggesting that ARR4 modulates essential functions in high acuity vision and downstream cellular signaling pathways that are not fulfilled or substituted by the coexpression of ARR1, despite its high expression levels in all mouse cones. Without normal ARR4 expression levels, cones slowly degenerate with increasing age, making this a new model to study age-related cone dystrophy. PMID- 26284547 TI - Enhancing Inflammation as an Adjuvant to Neovascular AMD Therapy. PMID- 26284546 TI - IL-18 Immunotherapy for Neovascular AMD: Tolerability and Efficacy in Nonhuman Primates. AB - PURPOSE: Age-related macular degeneration is the most common form of central retinal blindness in the elderly. Of the two end stages of disease, neovascular AMD-although the minority form-is the most severe. Current therapies are highly successful at controlling progression of neovascular lesions; however, a significant number of patients remain refractory to treatment and the development of alternative and additive therapies to anti-VEGFs is essential. METHODS: In order to address the translational potential of interleukin (IL)-18 for use in neovascular AMD, we initiated a nonhuman primate tolerability and efficacy study for the use of intravitreally (IVT) administered clinical grade human IL-18 (SB 485232). Cynomolgus monkeys were injected IVT with increasing doses of human IL 18 (two each at 1000, 3000, and 10,000 ng per eye). In tandem, 21 monkeys were administered nine laser burns in each eye prior to receiving IL-18 as an IVT injection at a range of doses. Fundus fluorescein angiography (FFA) was performed on days 8, 15, and 22 post injection and the development of neovascular lesions was assessed. RESULTS: We show intravitreal, mature, recombinant human IL-18 is safe and can reduce choroidal neovascular lesion development in cynomolgus monkeys. CONCLUSIONS: Based on our data comparing human IL-18 to current anti VEGF-based therapy, clinical deployment of IL-18 for neovascular AMD has the potential to lead to a new adjuvant immunotherapy-based treatment for this severe form of central blindness. PMID- 26284548 TI - Optical Density of Subretinal Fluid in Retinal Detachment. AB - PURPOSE: To investigate the changes over time in optical density (OD) characteristics of subretinal fluid (SRF) in rhegmatogenous retinal detachment (RRD) and their clinical relevance. METHODS: The study included patients with first-onset RRD and no history of intraocular illness who underwent optical coherence tomography (OCT) and whose OCT scans showed sufficient SRF for sampling (08/2013-09/2014). The highest quality B-scan (as graded by the OCT image acquisition software) containing SRF was analyzed. Optical density measurements were obtained using ImageJ. Optical density ratios (ODRs) were calculated as SRF OD divided by vitreous OD. Time from onset of RRD was determined by first signs of visual loss as described in the patient's anamnesis. Patients were divided into three groups by RRD duration: acute (<=1 week), subacute (between 1 week and 1 month), and chronic (>1 month). RESULTS: Thirty-five eyes (34 patients) met the inclusion criteria. The ODR measurement was significantly associated with RRD duration. The ODR had a significant (P < 0.0001) association with the 3-month postoperative visual acuity (VA). Vitreous OD did not differ significantly between the three groups. CONCLUSIONS: The increase over time in the ODR of the SRF in RRD might reflect a change in SRF composition and state of the retina. This, together with a significant association between preoperative ODR values and postoperative VA suggest its potential as a biological prognostic marker. PMID- 26284549 TI - Characterization of a New Epitope of IRBP That Induces Moderate to Severe Uveoretinitis in Mice With H-2b Haplotype. AB - PURPOSE: Experimental autoimmune uveitis (EAU) induced in mice using the retinal antigen interphotoreceptor retinoid binding protein (IRBP) is an animal model for posterior uveitis in humans. However, EAU induced by native IRBP protein or its widely used epitope amino acid residues 1 to 20 of human IRBP (hIRBP1-20) is inconsistent, often showing low scores and incidence. We found an urgent need to identify a better pathogenic epitope for the C57BL/6 strain. METHODS: Mice were immunized with uveitogenic peptides or with native bovine IRBP. Clinical and histological disease and associated immunological responses were evaluated. Truncated and substituted peptides, as well as bioinformatic analyses, were used to identify critical major histocompatibility complex (MHC)/T cell receptor (TCR) contact residues and the minimal core epitope. RESULTS: The new uveitogenic epitope of IRBP, amino acid residues 651 to 670 of human IRBP (LAQGAYRTAVDLESLASQLT [hIRBP651-670]) is uveitogenic for mice of the H-2b haplotype and elicits EAU with a higher severity and incidence in C57BL/6 mice than the previously characterized hIRBP1-20 epitope. Using truncated and substituted peptides, as well as bioinformatic analysis, we identified the critical contact residues with MHC/TCR and defined the minimal core epitope. This made it possible to design MHC tetramers and use them to detect epitope-specific T cells in the uveitic eye and in lymphoid organs of hIRBP651-670-immunized mice. CONCLUSIONS: Data suggest that hIRBP651-670 is an epitope naturally processed from a conserved region of native IRBP, potentially explaining its relatively high uveitogenicity. This epitope should be useful for basic and preclinical studies of uveitis in the C57BL/6 model and gives access to genetically engineered mice available on this background. PMID- 26284551 TI - Platelet-Derived Growth Factor-BB Enhances Adipogenesis in Orbital Fibroblasts. AB - PURPOSE: Platelet-derived growth factor (PDGF)-BB has been identified as important factor in pathogenesis of Graves' ophthalmopathy (GO). It stimulates proliferation, cytokine, and hyaluronan production, and thyrotropin receptor expression by orbital fibroblasts. Therefore, the PDGF-pathway has been proposed as a target for pharmacological intervention in GO. However, increased adipogenesis is another major pathological characteristic of GO and it is unknown whether this is affected by PDGF-BB. The aim of this study was to investigate the effect of PDGF-BB on adipocyte differentiation by orbital fibroblasts. METHODS: Orbital fibroblasts from five healthy controls and nine GO patients were collected. Adipogenesis was induced by culturing orbital fibroblasts in differentiation medium, either in the presence or absence of PDGF-BB. Adipogenesis was determined by Oil-Red-O staining, triglyceride measurement, and peroxisome proliferator-activated receptor (PPAR)-gamma mRNA expression. RESULTS: Platelet-derived growth factor-BB significantly enhanced adipocyte differentiation by orbital fibroblasts (Oil-Red-O staining [P < 0.0001], triglyceride measurement [P < 0.05], and PPAR-gamma mRNA expression [P < 0.05]). It enhanced IL-6 production early during differentiation, but the effect of PDGF BB on adipogenesis was independent of autocrine IL-6 signaling as it was not abrogated by IL-6-receptor-alpha neutralizing antibody. The clinically applicable tyrosine kinase inhibitor dasatinib and tyrphostin AG1296, which both block PDGF receptor tyrosine kinase activity, inhibited PDGF-BB-enhanced adipogenesis (P < 0.05) in orbital fibroblasts. Moreover, dasatinib reduced PPAR-gamma mRNA expression in cultured GO orbital tissue. CONCLUSIONS: Platelet-derived growth factor-BB enhances adipogenesis in orbital fibroblasts, and, thus, may contribute to adipose tissue expansion in GO. Therefore, the PDGF-signaling cascade may represent a target of therapy to interfere with adipogenesis in GO. PMID- 26284550 TI - MMP14 Cleavage of VEGFR1 in the Cornea Leads to a VEGF-Trap Antiangiogenic Effect. AB - PURPOSE: To determine the possible antiangiogenic effect of metalloproteinase (MMP) 14 cleavage of vascular endothelial growth factor receptor 1 (VEGFR1) in the cornea. METHODS: Recombinant mouse (rm) VEGFR1 was incubated with various concentrations of recombinant MMP14 to examine proteolysis in vitro. The reaction mixture was analyzed by SDS-PAGE and stained with Coomassie blue. The fragments resulting from rmVEGFR1 cleavage by MMP14 were subjected to Edman degradation, and the amino acid sequences were aligned with rmVEGFR1 sequences. Surface plasmon resonance was used to determine the equilibrium dissociation constant (KD) between MMP14 and rmVEGFR1. The KD value of rmVEGFR1 and the 59.8-kDa cleavage product binding to VEGF-A165 was also determined. Cell proliferation assays were performed in the presence of VEGF-A165 plus the 59.8-kDa VEGFR1 fragment or VEGF-A165 alone. RESULTS: Matrix metalloproteinase 14 binds and cleaves rmVEGFR1 to produce 59.8-kDa (N-terminal fragment, Ig domains 1-5), 35 kDa (C-terminal fragment containing IgG and His-tag), and 21-kDa (Ig domains 6-7) fragments. The 59.8-kDa fragment showed binding to VEGF-A165 and inhibited VEGF induced endothelial cell mitogenesis. CONCLUSIONS: Our findings suggest that VEGFR1 cleavage by MMP14 in the cornea leads to a VEGF-trap effect, reducing the proangiogenic effect of VEGF-A165, thereby reducing corneal angiogenesis. PMID- 26284552 TI - Evaluation of Chitosan/Aptamer Targeting TGF-beta Receptor II Thermo-Sensitive Gel for Scarring in Rat Glaucoma Filtration Surgery. AB - PURPOSE: This study was designed to develop a chitosan (CS) thermo-sensitive gel combined with aptamer S58 targeting transforming growth factor-beta receptor II (TGF-beta RII) and to investigate the antifibrotic effects of CS/S58 gel in a rat glaucoma filtration surgery (GFS) model. METHODS: In vitro aptamer S58 release rate from the CS/S58 gel were detected, and the effect of mitomycin-C (MMC), TGF beta2, CS, or CS/S58 gel on wound healing were investigated in a rat GFS model by detecting scar-related factors and the involved inflammatory response. The levels of collagen I and alpha-smooth muscle actin (alpha-SMA) were detected by immunohistochemistry and Western blotting. RESULTS: The control and TGF-beta2 eyes exhibited densely packed collagen fibers with no evidence of filtration after day 7. The pronounced increase in filtration efficiency was associated with thinner fibers, and a loosely organized subconjunctival matrix was observed in CS/S58 gel-treated eyes. The levels of collagen I and alpha-SMA were downregulated in CS/S58 gel-treated eyes. Conjunctival fibroblast proliferation and the inflammation response were also suppressed in the CS/S58 gel-treated group. CONCLUSIONS: This study presents evidence that the antifibrotic effect of chitosan in combination with aptamer S58 is superior to chitosan alone in a rat GFS model. Chitosan/S58 gel may be considered to be a promising antifibrotic agent for a local drug therapy. PMID- 26284553 TI - Comparison of Longitudinal Changes in Functional and Structural Measures for Evaluating Progression of Glaucomatous Optic Neuropathy. AB - PURPOSE: We compared longitudinal changes in functional and structural measures in eyes with glaucomatous optic neuropathy. METHODS: Circumpapillary retinal nerve fiber layer thickness (cpRNFL) and macular ganglion cell complex thickness (mGCC) were measured using spectral-domain optical coherence tomography (SD-OCT; RTVue). The Spectralis HRA+OCT instrument also was used to measure cpRNFL, and Heidelberg retina tomography II (HRT) and standard automated perimetry (SAP) were performed. Assessments were performed every 3 months over several years. Linear mixed modeling was used to evaluate the rate of change in each measure. RESULTS: Totals of 1406 RTVue, 1366 Spectralis, 1245 HRT, and 1392 SAP measurements were analyzed. Average baseline SAP mean deviation (MD) was -6.24 +/- 5.46 dB. Linear mixed modeling revealed that SAP MD changed by -0.23 dB/y (95% confidence interval [CI], -0.34 to -0.12 dB/y). Significant negative trends also were detected in cpRNFL (RTVue, -0.41 MUm/y [95% CI, -0.67 to -0.16 MUm/y]; Spectralis, -1.36 MUm/y [95% CI, -1.65 to -1.07 MUm/y]; and mGCC (RTVue, -0.47 MUm/y [95% CI, -0.64 to -0.30 MUm/y]). Disc rim area remained constant over time (HRT, -0.01 mm2/y [95% CI, -0.03 to 0.01 mm2/y]). The SAP MD, RTVue mGCC, and Spectralis cpRNFL showed the fastest changes in the inferior retina (superior visual field), while RTVue cpRNFL changed the fastest in the superior retina. CONCLUSIONS: Functional (SAP) and structural (SD-OCT) testing can detect longitudinal changes of glaucomatous optic neuropathy, but in different ways. PMID- 26284554 TI - Gremlin Induces Ocular Hypertension in Mice Through Smad3-Dependent Signaling. AB - PURPOSE: Transforming growth factor-beta2 induces extracellular matrix (ECM) remodeling, which likely contributes to the defective function of the trabecular meshwork (TM) leading to glaucomatous ocular hypertension. Bone morphogenetic proteins (BMPs) inhibit these profibrotic effects of TGFbeta2. The BMP antagonist gremlin is elevated in glaucomatous TM cells and increases IOP in an ex vivo perfusion culture model. The purpose of this study was to determine whether gremlin regulates ECM proteins in the TM, signals through the Smad3-dependent pathway, and induces ocular hypertension in mice. METHODS: Ad5.Gremlin or Ad5.TGFbeta2 was injected intravitreally into one eye of each mouse. Intraocular pressure measurements were taken using a TonoLab tonometer. Gremlin, TGFbeta2, fibronectin (FN), and collagen-1 (Col-1) expression in the TM was determined by immunofluorescence, Western immunoblot, and quantitative (q)PCR analyses. RESULTS: Ad5.Gremlin or Ad5.TGFbeta2 each caused significant IOP elevation in mice. Immunofluorescence and Western blot analysis demonstrated that gremlin and TGFbeta2 reciprocally increased the expression of each other, and both increased FN expression in the TM and surrounding tissues. Ad5.Gremlin elevated IOP and increased Fn and Col-1 gene expression in the TM of Smad3 wild-type (WT) mice, but had no effect in Smad3 HET or Smad3 KO mice. CONCLUSIONS: Our results demonstrate that intravitreal injections of either Ad5.Gremlin or Ad5.TGFbeta2 elevate IOP and upregulate the ECM protein FN in the TM of mice. These data show that gremlin signals through the Smad3-dependent pathway in the TM to elevate IOP. We determined for the first time gremlin's role in inducing ocular hypertension in an in vivo model system. PMID- 26284555 TI - Extent of Detached Retina and Lens Status Influence Intravitreal Protein Expression in Rhegmatogenous Retinal Detachment. AB - PURPOSE: The aim of the study was to compare intravitreal cytokines and chemokines to clinical parameters in patients with rhegmatogenous retinal detachment (RRD). METHODS: In this prospective study vitreous samples were taken undiluted from 60 patients with RRD and 20 age-matched controls with idiopathic epiretinal membranes at the beginning of primary vitrectomy. The following clinical parameters were assessed from RRD patients prior to surgery: number of quadrants detached, RD height, lens status, symptom duration, and refractive power. Concentrations of 40 different proteins in the vitreous of RRD eyes were measured by multiplex protein array, compared with controls and correlated to clinical parameters. RESULTS: Ten cytokines and chemokines were significantly upregulated in the vitreous of RRD eyes compared with controls (tissue inhibitors of metalloproteinases [TIMP]-1 and -2, macrophage inflammatory protein [MIP] 1alpha, monocyte chemoattractant protein [MCP]-1, IL-6, and -8, inducible protein (IP)-10, brain-derived neurotrophic factor [BDNF], TGFbeta-3, and platelet derived growth factor [PDGF]-AB/BB). Linear regression analysis revealed that IL 8 and TGFbeta-3 increased with the number of retinal quadrants detached, while TIMP-1 rose in eyes with greater RD heights. Concentrations of IP-10 and myeloperoxidase (MPO) peaked in eyes with two or more quadrants detached, while TIMP-2 was highest expressed in the vitreous of eyes with great RD height. In pseudophakic eyes with higher detachment height levels of vascular cell adhesion molecule (VCAM)-1 were significantly increased, while neural cell adhesion molecule (NCAM) was decreased in pseudophakic patients with shallow RD height. CONCLUSIONS: Extent of RRD and lens status significantly influence intravitreal proinflammatory, profibrotic, and proapoptotic protein expression. These data contribute to the fundamental understanding of pathophysiological mechanisms in RRD and may serve as a basis for development of adjunct therapeutics to facilitate functional restoration. PMID- 26284557 TI - Assessment of Lens Center Using Optical Coherence Tomography, Magnetic Resonance Imaging, and Photographs of the Anterior Segment of the Eye. AB - PURPOSE: To determine the nearest marker for evaluating the center of the crystalline lens using optical coherence tomography (OCT), magnetic resonance imaging (MRI), and photographs. METHODS: Optical coherence tomography scans of human eyes were obtained in vivo during femtosecond laser-assisted cataract surgery. From axial and sagittal images, the distance of the angle center (AC) and pupil center (PC) from the scanned capsule center (SCC) was calculated. From pre- and postoperative photographs, the distance of the PC and limbal center (LC) from the intraocular lens (IOL) center was calculated, and distance between each center on the lens equatorial plane was compared. After combination of pre- and postoperative images, we arranged the centers in order of distance from the IOL center. High-resolution MRI was performed in pig eyes ex vivo to confirm the exact location of the lens center relative to other centers. RESULTS: In human OCT scans and photographs (n = 76), the IOL center to AC distance was 0.22 +/- 0.13 mm, the IOL center to SCC distance was 0.22 +/- 0.12 mm, the IOL center to PC distance was 0.25 +/- 0.17 mm, and the IOL center to LC distance was 0.30 +/- 0.18 mm. The AC and SCC were significantly closer to the IOL center than the PC or LC. In MRI (n = 54 images), the lens center to AC distance was 0.90 +/- 0.58 mm, and the lens center to PC distance was 1.53 +/- 0.87 mm (Delta distance = 0.63 +/- 0.69 mm, P = 0.000). CONCLUSIONS: Optical coherence tomography, MRI, and photographs of the anterior segment revealed that the AC is the nearest marker to the center of the lens equator. PMID- 26284558 TI - Reactivation of the PI3K/Akt Signaling Pathway by the Bisperoxovanadium Compound bpV(pic) Attenuates Photoreceptor Apoptosis in Experimental Retinal Detachment. AB - PURPOSE: Phosphatase and tensin homology deleted on chromosome 10 (PTEN) is crucial in neuronal apoptosis. This study evaluated the role of PTEN in photoreceptor cell apoptosis caused by retinal detachment (RD). METHODS: A rat model of RD was established, and PTEN expression changes were detected at different time points by Western blotting and immunofluorescence. Some of the rats were given subretinal injections of bisperoxovanadium compound (bpV[pic]) after RD. We documented the expression and distribution of phospho-Akt (p-Akt) and B-cell lymphoma 2 (Bcl-2) in the retina by Western blot analysis and immunofluorescence. Levels of phosph-phosphoinositide-dependent kinase 1 (p PDK1), phospho-Bcl-2 death promotor (p-BAD), cytosolic cytochrome c (Cyt c), and cleaved Caspase-3 were detected by Western blotting. We measured phosphatidylinositol 3,4,5-triphosphate (PIP3) by ELISA. Apoptosis of photoreceptors was detected using the TUNEL assay. The thickness of the outer nuclear layer (ONL) also was recorded. RESULTS: The expression of PTEN gradually increased after RD, peaking at 3 days and then decreasing to normal by 7 days after RD. Subretinal injection of bpV(pic) effectively reduced the apoptosis of photoreceptors and preserved the retinal thickness of the ONL after RD. Compared to vehicle-treated RD groups, levels of p-Akt and p-PDK1 were significantly upregulated in bpV-treated RD groups. In addition, bpV treatment increased the levels of p-BAD and Bcl-2, and decreased the expression levels of cytosolic Cyt c and cleaved caspase-3 after RD. CONCLUSIONS: Phosphatase and tensin homology deleted on chromosome 10 (PTEN) participates in the apoptosis of photoreceptors after RD. Blocking PTEN may reactivate the PI3K/Akt pathway and attenuate photoreceptor apoptosis by suppressing the mitochondrial pathway. PMID- 26284556 TI - Protective Effects of L-Carnitine Against Oxidative Injury by Hyperosmolarity in Human Corneal Epithelial Cells. AB - PURPOSE: L-carnitine suppresses inflammatory responses in human corneal epithelial cells (HCECs) exposed to hyperosmotic stress. In this study, we determined if L-carnitine induces this protective effect through suppression of reactive oxygen species (ROS)-induced oxidative damage in HCECs. METHODS: Primary HCECs were established from donor limbal explants. A hyperosmolarity dry-eye model was used in which HCECs are cultured in 450 mOsM medium with or without L carnitine for up to 48 hours. Production of reactive oxygen species (ROS), oxidative damage markers, oxygenases and antioxidative enzymes were analyzed by 2',7'-dichlorofluorescein diacetate (DCFDA) kit, semiquantitative PCR, immunofluorescence, and/or Western blotting. RESULTS: Reactive oxygen species production increased in HCECs upon substitution of the isotonic medium with the hypertonic medium. L-carnitine supplementation partially suppressed this response. Hyperosmolarity increased cytotoxic membrane lipid peroxidation levels; namely, malondialdehyde (MDA) and hydroxynonenal (HNE), as well as mitochondria DNA release along with an increase in 8-OHdG and aconitase-2. Interestingly, these oxidative markers were significantly decreased by coculture with L carnitine. Hyperosmotic stress also increased the mRNA expression and/or protein production of heme oxygenase-1 (HMOX1) and cyclooxygenase-2 (COX2), but inhibited the levels of antioxidant enzymes, superoxide dismutase-1 (SOD1), glutathione peroxidase-1 (GPX1), and peroxiredoxin-4 (PRDX4). However, L-carnitine partially reversed this altered imbalance between oxygenases and antioxidant enzymes induced by hyperosmolarity. CONCLUSIONS: Our findings demonstrate for the first time that L-carnitine protects HCECs from oxidative stress by lessening the declines in antioxidant enzymes and suppressing ROS production. Such suppression reduces membrane lipid oxidative damage markers and mitochondrial DNA damage. PMID- 26284560 TI - Tolerance and Relative Utility: Two Proposed Indices for Comparing Change in Clinical Measurement Noise Between Different Populations (Repeatability) or Measurement Methods (Agreement). AB - Reaching a consensus in terms of interchangeability and utility (i.e., disease detection/monitoring) of a medical device is the eventual aim of repeatability and agreement studies. The aim of the tolerance and relative utility indices described in this report is to provide a methodology to compare change in clinical measurement noise between different populations (repeatability) or measurement methods (agreement), so as to highlight problematic areas. No longitudinal data are required to calculate these indices. Both indices establish a metric of least to most effected across all parameters to facilitate comparison. If validated, these indices may prove useful tools when combining reports and forming the consensus required in the validation process for software updates and new medical devices. PMID- 26284559 TI - Perceptual Visual Distortions in Adult Amblyopia and Their Relationship to Clinical Features. AB - PURPOSE: Develop a paradigm to map binocular perceptual visual distortions in adult amblyopes and visually normal controls, measure their stability over time, and determine the relationship between strength of binocular single vision and distortion magnitude. METHODS: Perceptual visual distortions were measured in 24 strabismic, anisometropic, or microtropic amblyopes (interocular acuity difference >= 0.200 logMAR or history of amblyopia treatment) and 10 controls (mean age 27.13 +/- 10.20 years). The task was mouse-based target alignment on a stereoscopic liquid crystal display monitor, measured binocularly five times during viewing dichoptically through active shutter glasses, amblyopic eye viewing cross-hairs, fellow eye viewing single target dots (16 locations within central 5 degrees ), and five times nondichoptically, with all stimuli visible to either eye. Measurements were repeated over time (1 week, 1 month) in eight amblyopic subjects, evaluating test-retest reliability. Measurements were also correlated against logMAR visual acuity, horizontal prism motor fusion range, Frisby/Preschool Randot stereoacuity, and heterophoria/heterotropia prism cover test measurement. RESULTS: Sixty-seven percent (16/24) of amblyopes had significant perceptual visual distortions under dichoptic viewing conditions compared to nondichoptic viewing conditions and dichoptic control group performance. Distortions correlated with the strength of motor fusion (r = 0.417, P = 0.043) and log stereoacuity (r = 0.492, P = 0.015), as well as near angle of heterotropic/heterophoric deviation (r = 0.740, P < 0.001), and, marginally, amblyopia depth (r = 0.405, P = 0.049). Global distortion index (GDI, mean displacement) remained, overall, consistent over time (median change in GDI between baseline and 1 week = -0.03 degrees , 1 month = -0.08 degrees ; x-axis Z = 4.4256, P < 0.001; y-axis Z = 5.0547, P < 0.001). CONCLUSIONS: Perceptual visual distortions are stable over time and associated with poorer binocular function, greater amblyopia depth, and larger angles of ocular deviation. Assessment of distortions may be relevant for recent perceptual learning paradigms specifically targeting binocular vision. PMID- 26284561 TI - Gut microbiota: Ganoderma lucidum, a new prebiotic agent to treat obesity? AB - Modulation of the gut microbiota is one of the promising tools to tackle obesity. Chang and colleagues have recently shown that an extract of the mushroom Ganoderma lucidum, a traditional remedy in Asia, can reduce obesity in mice by modulating the gut microbiota, thereby exerting a prebiotic effect. PMID- 26284563 TI - Malnutrition: New mouse model of EE. PMID- 26284562 TI - Biologic agents for IBD: practical insights. AB - Six biologic agents are currently approved for the treatment of IBD: four anti TNF agents (infliximab, adalimumab, golimumab and certolizumab pegol) and two anti-integrin agents (natalizumab and vedolizumab). In Crohn's disease and ulcerative colitis refractory to standard medications, treatment choice among available biologic agents can be challenging. Several parameters should be taken into account to help physicians through the decision-making process, including the comparative effectiveness and long-term safety profile, availability and labelling in the prescriber's country, international guidelines, and cost, as well as patient preferences (such as the route of administration). Herein, we provide practical insights on the use of biologic agents in IBD. The results of head-to-head trials between biologic agents are eagerly awaited to guide decision making regarding the choice of first-line biologic agents and to determine whether switching within the same drug class or swapping (switching out of the drug class) is preferable after primary or secondary loss of response to the first biologic agent. In the near future, treatment algorithms might evolve with the launch of new drugs (such as ustekinumab, tofacitinib and etrolizumab) and the increased use of biosimilars. PMID- 26284564 TI - Oesophageal cancer: Neoadjuvant chemoradiotherapy and surgery superior to surgery alone. PMID- 26284565 TI - Acidic phospholipid-independent interaction of Yas3p, an Opi1-family transcriptional repressor of Yarrowia lipolytica, with the endoplasmic reticulum. AB - In the n-alkane-assimilating yeast Yarrowia lipolytica, the transcription of ALK1, encoding cytochrome P450, that catalyses n-alkane hydroxylation is activated by a complex composed of Yas1p and Yas2p via a promoter element, ARE1, in response to n-alkanes. An Opi1-family transcription factor, Yas3p, represses the transcription by binding to Yas2p in the nucleus when cultured in glucose containing medium, but it is localized to the ER, presumably through interaction with acidic phospholipids, phosphatidic acid and/or phospho inositides, when cultured in n-alkane-containing medium. Here, to elucidate the mechanisms regulating the localization of Yas3p, point and deletion mutants of Yas3p were constructed and analysed. The substitution of Trp(360) and Cys(361) by Arg abrogated the localization of Yas3p to the ER and decreased ARE1-mediated transcriptional activation by n-alkane. A Yas3p truncation mutant consisting of residues 259-422 did not bind to acidic phospholipids, but it was localized to the ER in the presence of n-alkane, implying the acidic-phospholipid-independent recruitment of this mutant to the ER in response to n-alkane. The W360R and C361R substitutions in this truncation mutant abolished its localization to the ER. The results suggest that these residues are implicated in the acidic phospholipid independent interaction of Yas3p to the ER. PMID- 26284566 TI - Active Transport, Physical Activity, and Distance Between Home and School in Children and Adolescents. AB - BACKGROUND: The distance between home and school is the most consistent predictor of active transport in youth: the closer an individual lives to school, the more likely they are to use active transport. While this suggests that it is preferable to live as close to school as possible, the limited physical activity accumulated during short trips may not offer substantial benefits to active transporters. METHODS: The current study investigated the predicted physical activity benefits associated with a range of home-school distances in 595 young people aged 5 to 16 years (Years 1 to 11). Physical activity was measured using sealed pedometers over 7 days. Participants' home addresses and usual transport mode to and from school were collected via a questionnaire completed by parents (Years 1 to 6) and participants (Years 7 to 11). RESULTS: A nonlinear relationship between predicted weekday activity and distance was detected, such that the high probability of active transport at short distances was offset by the low physical activity associated with walking short distances. CONCLUSIONS: A distance of approximately 2 km was associated with the best physical activity outcomes related to active transport (9% to 15% increase on weekdays). These findings have potential implications for future interventions and for planning residential developments or facilities. PMID- 26284567 TI - Duration of tetanus immunoglobulin G titres following basic immunisation of horses. AB - REASONS FOR PERFORMING STUDY: Recommendations for prophylactic vaccination against tetanus in horses vary greatly between countries and have scarce scientific support in the peer-reviewed literature. In human medicine, recommended booster vaccination intervals are also very variable, but are considerably longer than for horses. More information is needed about the duration of immunity induced by modern vaccines. OBJECTIVES: To investigate if the duration of antibody titres previously determined to be protective against tetanus differ from what is indicated by recommended vaccination intervals for horses. STUDY DESIGN: Prospective seroconversion study. METHODS: Thirty-four horses were enrolled for basic immunisation with an ISCOM Matrix-combination vaccine (Equilis Prequenza Te). Horses received the first vaccination at age 5-11 months, and the second dose 4 weeks later. A third vaccine dose was given 15-17 months after the second dose. Serum tetanus antibody titres were analysed by toxin-binding enzyme-linked immunosorbent assay 2 weeks as well as 14-16 months after the second dose. After the third vaccine dose, titres were checked once yearly for 3 years. Results were described by age and level of antibody titre at first sampling. RESULTS: Two weeks after the second dose, all horses (34/34) had antibody levels that exceeded the limit of detection, 0.04 iu/ml. After 16 months the levels were above 0.04 iu/ml in 28/33 horses, the remaining 5 horses potentially had suboptimal protection against tetanus. After the third vaccine dose antibody levels remained above 0.04 iu/ml in 25/26 horses for 1 year, 16/16 horses for 2 years, and 8/8 horses for 3 years. CONCLUSIONS: Horses that undergo basic immunisation with 3 doses of vaccine after age 5 months are likely to have serum antibody titres consistent with protection against tetanus for more than 3 years. Current guidelines for tetanus prophylaxis should be revised. PMID- 26284569 TI - Aromaticity, quantum multimolecular polyhedra, and quantum QSPR fundamental equation. AB - A causal relation connecting aromaticity with the current aromaticity descriptors used in the literature and compliant with a quantum mechanics theoretical background is described. PMID- 26284570 TI - Virus-specific T-cell therapy in solid organ transplantation. AB - This article reviews the current state of T-cell therapy as therapeutic option for virus-associated diseases against the background of the most common viral complications and their standard treatment regimens after SOT. The available data of clinical T-cell trials in SOT are summarized. References to the hematopoietic stem cell transplantation are made if applicable data in SOT are not available and their content was considered likewise valid for cell therapy in SOT. Moreover, aspects of different manufacturing approaches including beneficial product characteristics and the importance of GMP compliance are addressed. PMID- 26284571 TI - Comparing the prognostic value of risk stratifying models for patients with lower risk myelodysplastic syndromes: Is one model better? AB - Some patients classified as having lower-risk (LR)-disease by the International Prognostic Scoring System (IPSS) fare more poorly than predicted. We examined the prognostic utility of IPSS, the MD Anderson LR-Prognostic System (LR-PSS), and the revised IPSS (IPSS-R) in a large cohort of patients classified as having IPSS LR-MDS in the MDS Clinical Research Consortium database. Actual overall survival (OS) was assessed in patients with IPSS LR-MDS (i.e. low and intermediate-1) using Kaplan-Meier methods. Harrell's c index (HCI) and Akaike information criteria (AIC) were used to compare the models. Median OS of 1,140 eligible patients was 47 months (95% CI, 44-52). Median follow-up was 62 months. HCI values indicating the discriminatory power of the models (higher is better) were better for LR-PSS (0.74, 95% CI, 0.70-0.78) than IPSS-R (0.64, 95% CI, 0.60-0.67) and IPSS (0.64, 95% CI, 0.60-0.68). Similarly, AIC values indicating the goodness of the fit were better for LR-PSS than IPSS-R and IPSS (8,110, 8,147, and 8,150, respectively, lower is better). LR-PSS assigned 25.1% and 37.4% of patients with IPSS LR-MDS into LR-PSS Category 3 and IPSS-R Categories >=Intermediate, respectively. Of 291 patients (25.5%) who survived <=24 months from diagnosis, only 37.1% and 45% were classified as LR-PSS category 3 and IPSS-R categories >=Intermediate, respectively (P = 0.06). While both LR-PSS and IPSS-R distinguish groups with varied survival outcome among patients with IPSS LR-MDS, both tools fail to identify a significant subset with poor OS. Future studies should assess whether patients identified as at increased risk will benefit from earlier interventions with disease-modifying therapies. PMID- 26284568 TI - MicroRNA-Based Therapeutic Strategies for Targeting Mutant and Wild Type RAS in Cancer. AB - MicroRNAs (miRs) have been causally implicated in the progression and development of a wide variety of cancers. miRs modulate the activity of key cell signaling networks by regulating the translation of pathway component proteins. Thus, the pharmacological targeting of miRs that regulate cancer cell signaling networks, either by promoting (using miR-supplementation) or by suppressing (using antisense oligonucleotide-based strategies) miR activity is an area of intense research. The RAS-extracellular signal regulated kinase (ERK) pathway represents a major miR-regulated signaling network that endows cells with some of the classical hallmarks of cancer, and is often inappropriately activated in malignancies by somatic genetic alteration through point mutation or alteration of gene copy number. In addition, recent progress indicates that many tumors may be deficient in GTPase activating proteins (GAPs) due to the collaborative action of oncogenic miRs. Recent studies also suggest that in tumors harboring a mutant RAS allele there is a critical role for wild type RAS proteins in determining overall RAS-ERK pathway activity. Together, these two advances comprise a new opportunity for therapeutic intervention. In this review, we evaluate miR-based therapeutic strategies for modulating RAS-ERK signaling in cancers; in particular for more direct modulation of RAS-GTP levels, with the potential to complement current strategies to yield more durable treatment responses. To this end, we discuss the potential for miR-based therapies focused on three prominent miRs including the pan-RAS regulator let-7 and the GAP regulator comprised of miR-206 and miR-21 (miR-206/21). PMID- 26284572 TI - Interview-based Qualitative Research in Emergency Care Part II: Data Collection, Analysis and Results Reporting. AB - Qualitative methods are increasingly being used in emergency care research. Rigorous qualitative methods can play a critical role in advancing the emergency care research agenda by allowing investigators to generate hypotheses, gain an in depth understanding of health problems or specific populations, create expert consensus, and develop new intervention and dissemination strategies. In Part I of this two-article series, we provided an introduction to general principles of applied qualitative health research and examples of its common use in emergency care research, describing study designs and data collection methods most relevant to our field (observation, individual interviews, and focus groups). Here in Part II of this series, we outline the specific steps necessary to conduct a valid and reliable qualitative research project, with a focus on interview-based studies. These elements include building the research team, preparing data collection guides, defining and obtaining an adequate sample, collecting and organizing qualitative data, and coding and analyzing the data. We also discuss potential ethical considerations unique to qualitative research as it relates to emergency care research. PMID- 26284573 TI - Building International Sustainable Partnerships in Occupational Therapy: A Case Study. AB - Occupational therapy practitioners frequently identify opportunities for international practice. The World Health Organization and the World Federation of Occupational Therapists have encouraged occupational therapists to address transnational issues, social inclusion, and equal access to opportunities grounded in meaningful occupation (WFOT, 2012). This case study describes a partnership between two U.S. schools of occupational therapy and a Cuban community based pediatric clinic. It examines the dynamics that have sustained the partnership despite political, economic, and logistical barriers. The literature is scrutinized to show how this case study fits into other accounts of collaborative international partnerships. Particularly, it investigates structural and institutional conditions that shape international sustainable partnerships. In doing so, we answer the following questions: (1) Under which circumstances do international partnerships emerge and flourish? (2) What structural and institutional conditions shape international sustainable partnerships? And (3) How do partners perceive and experience the bilateral international partnership? It also discusses and illustrates the foundations and development of international partnerships that succeed. Through the use of a case study we illustrate the development of this partnership. Finally, we consider the next steps of this particular sustainable and collaborative international partnership. PMID- 26284574 TI - Crossing Borders: A Qualitative Study of How Occupational Therapy Educators and Scholars Develop and Sustain Global Partnerships. AB - The World Federation of Occupational Therapists (WFOT) and the American Occupational Therapy Association promote a globally connected profession that responds to the needs of our diverse societies. Global partnerships are grounded on the principle that cross-cultural experiences are enriching and provide mutual benefits. The purpose of this study was to uncover how occupational therapy educators and scholars perceive and experience (1) developing and sustaining global partnerships and (2) lessons learned. In this qualitative study, 30 occupational therapy educators and researchers completed an online survey. Eight participated in an interview. Results found major themes that help develop and sustain partnerships: building relationship of trust and respect, communicating effectively, cultivating cultural competence, sharing power and resources with collaborators and creating a context for reciprocal learning. Lessons learned include a call to walking humbly, building relationships of trust and respect, establishing open and honest communication, supporting local solutions to local problems, ensuring equality of resources and learning from their global partners. The findings suggest that global partnerships have the potential to transform both partners if the partners engage with mutual understanding and respect. Limitations of this study include a small sample size and participant's pool limited to occupational therapists from United States. Recommendations for future research include qualitative studies to identify model occupational therapy programmes that sustain global partnerships using a diverse sample of international occupational therapy educators and researchers. PMID- 26284575 TI - Effects of extreme weather events and legume presence on mycorrhization of Plantago lanceolata and Holcus lanatus in the field. AB - Little is known about direct and indirect effects of extreme weather events on arbuscular mycorrhizal fungi (AMF) under field conditions. In a field experiment, we investigated the response of mycorrhization to drought and heavy rain in grassland communities. We quantified AMF biomass in soil, mycorrhization of roots of the grass Holcus lanatus and the forb Plantago lanceolata, as well as plant performance. Plants were grown in four-species communities with or without a legume. We hypothesised that drought increases and heavy rain decreases mycorrhization, and that higher mycorrhization will be linked to improved stress resistance and higher biomass production. Soil AMF biomass increased under both weather extremes. Heavy rain generally benefitted plants and increased arbuscules in P. lanceolata. Drought neither reduced plant performance nor root mycorrhization. Arbuscules increased in H. lanatus several weeks after drought, and in P. lanceolata several weeks after heavy rain spells. These long-lasting effects of weather events on mycorrhization highlight the indirect influence of climate on AMF via their host plant. Legume presence increased plant community biomass, but had only minor effects on mycorrhization. Arbuscule colonisation was negatively correlated with senescence during the dry summer. Mycorrhization and biomass production in P. lanceolata were positively related. However, increased mycorrhization was related to less biomass in the grass. AMF mycelium in soil might generally increase under extreme events, root colonisation, however, is host species specific. This might amplify community shifts in grassland under climate change by further increasing stress resistance of species that already benefit from changed precipitation. PMID- 26284576 TI - How else can we study sex differences in early infancy? AB - This paper revisits group difference and individual variability in birth weight, head size, Apgar score, and motor performance in neonatal and 8-month-old males and females using a large existing data set. The goal is primarily theoretical- to reframe existing analyses with an eye toward designing and executing more predictive analyses in the future. 3D graphing to visualize both the areas of overlap and regions of disparity between boys and girls has been used. A two-step cluster analysis of boys and girls together revealed three clusters. One was almost equally divided between boys and girls, but a second was highly enriched for boys and the third highly skewed toward girls. The relationship between cluster membership and Bayley motor scores at 8 months tested the hypothesis that initial differences that have no sex-related behavioral content might start processes that produce later sex-related differences. Initially, parental belief systems may be less important than infant care patterns evoked by basic size and health characteristics, even though later parental behaviors assume a decidedly gendered pattern. PMID- 26284578 TI - Corrigendum. PMID- 26284579 TI - The dynamic anatomy and patterning of skin. AB - The skin is often viewed as a static barrier that protects the body from the outside world. Emphasis on studying the skin's architecture and biomechanics in the context of restoring skin movement and function is often ignored. It is fundamentally important that if skin is to be modelled or developed, we do not only focus on the biology of skin but also aim to understand its mechanical properties and structure in living dynamic tissue. In this review, we describe the architecture of skin and patterning seen in skin as viewed from a surgical perspective and highlight aspects of the microanatomy that have never fully been realized and provide evidence or concepts that support the importance of studying living skin's dynamic behaviour. We highlight how the structure of the skin has evolved to allow the body dynamic form and function, and how injury, disease or ageing results in a dramatic changes to the microarchitecture and changes physical characteristics of skin. Therefore, appreciating the dynamic microanatomy of skin from the deep fascia through to the skin surface is vitally important from a dermatological and surgical perspective. This focus provides an alternative perspective and approach to addressing skin pathologies and skin ageing. PMID- 26284580 TI - Interstitial microdeletions including the chromosome band 4q13.2 and the UBA6 gene as possible causes of intellectual disability and behavior disorder. AB - The few proximal 4q chromosomal aberrations identified in patients with neurodevelopmental phenotypes that have been published to date are variable in type, size and breakpoints and, therefore, encompass different chromosome bands and genes, making the establishment of genotype-phenotype correlations a challenging task. Here, microarray-based copy number analysis allowed us the detection of two novel and partially overlapping deletions in two unrelated families. In Family 1, a 4q13.1-q13.2 deletion of 3.84 Mb was identified in a mother with mild intellectual disability and in her two children, both with mild intellectual disability and attention deficit hyperactivity disorder. In Family 2, a de novo 4q13.2-q13.3 deletion of 6.81 Mb was detected in a female patient, born to unaffected parents, with a diagnosis of mild intellectual disability, behavioral disorder and facial dysmorphism. The shortest region of overlap between these two aberrations is located at chromosome 4q13.2 and includes 17 genes amongst of which we suggest UBA6 (ubiquitin-like modifier-activating enzyme 6) as a strong candidate gene for these phenotypes. PMID- 26284581 TI - Defining Plasma MicroRNAs Associated With Cognitive Impairment In HIV-Infected Patients. AB - Human Immunodeficiency Virus (HIV)-infected individuals are at increased risk for developing neurocognitive disorders and depression. These conditions collectively affect more than 50% of people living with HIV/AIDS and adversely impact adherence to HIV therapy. Thus, identification of early markers of neurocognitive impairment could lead to interventions that improve psychosocial functioning and slow or reverse disease progression through improved treatment adherence. Evidence has accumulated for the role and function of microRNAs in normal and pathological conditions. We have optimized a protocol to profile microRNAs in body fluids. Using this methodology, we have profiled plasma microRNA expression for 30 age-matched, HIV-infected (HIV(+) ) patients and identified highly sensitive and specific microRNA signatures distinguishing HIV(+) patients with cognitive impairment from those without cognitive impairment. These results justify follow-on studies to determine whether plasma microRNA signatures can be used as a screening or prognostic tool for HIV(+) patients with neurocognitive impairment. J. Cell. Physiol. 231: 829-836, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26284582 TI - Oncogene- and drug resistance-associated alternative exon usage in acute myeloid leukemia (AML). AB - In addition to spliceosome gene mutations, oncogene expression and drug resistance in AML might influence exon expression. We performed exon-array analysis and exon-specific PCR (ESPCR) to identify specific landscapes of exon expression that are associated with DEK and WT1 oncogene expression and the resistance of AML cells to AraC, doxorubicin or azacitidine. Data were obtained for these five conditions through exon-array analysis of 17 cell lines and 24 patient samples and were extended through qESPCR of samples from 152 additional AML cases. More than 70% of AEUs identified by exon-array were technically validated through ESPCR. In vitro, 1,130 to 5,868 exon events distinguished the 5 conditions from their respective controls while in vivo 6,560 and 9,378 events distinguished chemosensitive and chemoresistant AML, respectively, from normal bone marrow. Whatever the cause of this effect, 30 to 80% of mis-spliced mRNAs involved genes unmodified at the whole transcriptional level. These AEUs unmasked new functional pathways that are distinct from those generated by transcriptional deregulation. These results also identified new putative pathways that could help increase the understanding of the effects mediated by DEK or WT1, which may allow the targeting of these pathways to prevent resistance of AML cells to chemotherapeutic agents. PMID- 26284583 TI - Maintenance chemotherapy in children with ALL exerts metronomic-like thrombospondin-1 associated anti-endothelial effect. AB - Maintenance chemotherapy is an important part of the treatment of ALL in children. It relies on the long-term oral administration of daily low-dose mercaptopurin and weekly low-dose methotrexate. Although it has been used in the clinic for decades, its mechanisms of action remain unclear. Here, we investigated different angiogenic and immune biomarkers to gain insights into the mechanisms of action of maintenance therapy in children with ALL. We thus monitored circulating endothelial cells (CEC), endothelial progenitor cells (EPC) and endothelial microparticles (EMP), pro-angiogenic factors (VEGF, VEGFR-1 and Ang-2), anti-angiogenic factor thrombospondin-1 (THBS1) and regulatory T lymphocytes (Treg) in 47 children with ALL during the maintenance phase of their treatment (at treatment initiation and after 6, 12 and 18 months). We observed a statistically significant decrease in EPC and EMP counts throughout the maintenance phase associated with a significant increase in THBS1 levels. No significant change was detected in other angiogenic markers or in Treg numbers.The results presented here indicate that maintenance therapy in children with ALL exerts its antitumor activity at least in part through anti-angiogenic effects, similar to those induced by metronomic chemotherapy. Larger studies are now warranted to validate these findings and determine their clinical implications. PMID- 26284585 TI - Inflammaging increases susceptibility to cigarette smoke-induced COPD. AB - Chronic obstructive pulmonary disease (COPD) is related to an abnormal chronic inflammatory response of the lung to mainly cigarette smoke (CS) and the disease risk is increased in aged individuals. The source of this chronic inflammation is due to the repeated and progressive activation of immune cells. We hypothesize that in a chronic CS-induced mouse model, the predisposition to COPD pathogenesis in aged mice is characterized by an elevated immune response compared to young animals. We measured several characteristics of COPD in young and old mice (2 and 12 months of age) exposed to CS for 3 months. CS-exposed aged mice exhibited increased lung compliance (0.061 +/- 0.008 vs. 0.055 +/- 0.006 ml/cm H2O, p < 0.01), emphysema development (35.36 +/- 0.71 vs. 25.31 +/- 0.005 MUm; p < 0.01) and airway remodeling (2.15 +/- 0.37 vs. 1.09 +/- 0.64 MUm3/MUm2; p < 0.01) compared to control animals, which was not seen in CS-exposed young mice. Quantification of lung tissue inflammation revealed a significantly greater volume of inducible bronchus-associated lymphoid tissue structures in aged mice after CS exposure (5.94 +/- 2.89 vs. 2.37 +/- 1.69 MUm3/MUm2; p < 0.01). Our results indicate that age-induced lung inflammation is further elevated after CS exposure in old mice, potentially via an age-induced change in immune cell susceptibility to CS thereby accelerating the pathophysiological hallmarks of COPD. PMID- 26284584 TI - Simvastatin and downstream inhibitors circumvent constitutive and stromal cell induced resistance to doxorubicin in IGHV unmutated CLL cells. AB - The immunoglobulin heavy-chain variable region (IGHV) mutational status is a strong determinant of remission duration in chronic lymphocytic leukemia (CLL). The aim of this work was to compare the multidrug resistance (MDR) signature of IGHV mutated and unmutated CLL cells, identifying biochemical and molecular targets potentially amenable to therapeutic intervention.We found that the mevalonate pathway-dependent Ras/ERK1-2 and RhoA/RhoA kinase signaling cascades, and the downstream HIF-1alpha/P-glycoprotein axis were more active in IGHV unmutated than in mutated cells, leading to a constitutive protection from doxorubicin-induced cytotoxicity. The constitutive MDR phenotype of IGHV unmutated cells was partially dependent on B cell receptor signaling, as shown by the inhibitory effect exerted by ibrutinib. Stromal cells further protected IGHV unmutated cells from doxorubicin by upregulating Ras/ERK1-2, RhoA/RhoA kinase, Akt, HIF-1alpha and P-glycoprotein activities. Mevalonate pathway inhibition with simvastatin abrogated these signaling pathways and reversed the resistance of IGHV unmutated cells to doxorubicin, also counteracting the protective effect exerted by stromal cells. Similar results were obtained via the targeted inhibition of the downstream molecules ERK1-2, RhoA kinase and HIF 1alpha.Therefore, targeting the mevalonate pathway and its downstream signaling cascades is a promising strategy to circumvent the MDR signature of IGHV unmutated CLL cells. PMID- 26284586 TI - mTOR inhibitors sensitize thyroid cancer cells to cytotoxic effect of vemurafenib. AB - Treatment options for advanced metastatic thyroid cancer patients are limited. Vemurafenib, a BRAFV600E inhibitor, has shown promise in clinical trials although cellular resistance occurs. Combination therapy that includes BRAFV600E inhibition and avoids resistance is a clinical need. We used an in vitro model to examine combination treatment with vemurafenib and mammalian target of rapamycin (mTOR) inhibitors, metformin and rapamycin. Cellular viability and apoptosis were analyzed in thyroid cell lines by trypan blue exclusion and TUNEL assays. Combination of vemurafenib and metformin decreased cell viability and increased apoptosis in both BCPAP papillary thyroid cancer cells and 8505c anaplastic thyroid cancer cells. This combination was also found to be active in vemurafenib resistant BCPAP cells. Changes in expression of signaling molecules such as decreased mTOR expression in BCPAP and enhanced inhibition of phospho-MAPK in resistant BCPAP and 8505c were observed. The second combination of vemurafenib and rapamycin amplified cell death in BCPAP cells. We conclude that combination of BRAFV600E and mTOR inhibition forms the basis of a treatment regimen that should be further investigated in in vivo model systems. Metformin or rapamycin adjuvant treatment may provide clinical benefits with minimal side effects to BRAFV600E-positive advanced thyroid cancer patients treated with vemurafenib. PMID- 26284587 TI - Differential involvement of RASSF2 hypermethylation in breast cancer subtypes and their prognosis. AB - Breast cancer is a heterogeneous disease that can be subdivided into clinical, histopathological and molecular subtypes (luminal A-like, luminal B-like/HER2 negative, luminal B-like/HER2-positive, HER2-positive, and triple-negative). The study of new molecular factors is essential to obtain further insights into the mechanisms involved in the tumorigenesis of each tumor subtype. RASSF2 is a gene that is hypermethylated in breast cancer and whose clinical value has not been previously studied. The hypermethylation of RASSF1 and RASSF2 genes was analyzed in 198 breast tumors of different subtypes. The effect of the demethylating agent 5-aza-2'-deoxycytidine in the re-expression of these genes was examined in triple negative (BT-549), HER2 (SK-BR-3), and luminal cells (T-47D). Different patterns of RASSF2 expression for distinct tumor subtypes were detected by immunohistochemistry. RASSF2 hypermethylation was much more frequent in luminal subtypes than in non-luminal tumors (p = 0.001). The re-expression of this gene by lentiviral transduction contributed to the differential cell proliferation and response to antineoplastic drugs observed in luminal compared with triple negative cell lines. RASSF2 hypermethylation is associated with better prognosis in multivariate statistical analysis (P = 0.039). In conclusion, RASSF2 gene is differently methylated in luminal and non-luminal tumors and is a promising suppressor gene with clinical involvement in breast cancer. PMID- 26284590 TI - Organic-free Anatase TiO2 Paste for Efficient Plastic Dye-Sensitized Solar Cells and Low Temperature Processed Perovskite Solar Cells. AB - Recently, the synthesis of fine TiO2 paste with organic-free binder emerged as an indispensable technique for plastic photovoltaics due to the low temperature processing requirement. In this study, pure anatase TiO2 nanoparticles and organic-free TiO2-sol were successfully synthesized individually in organic-free solution. By mixing the pure anatase TiO2 with the newly developed TiO2-sol binder, mechanically robust and well-interconnected TiO2 films were prepared via UV-irradiation at low temperature for applications in plastic dye-sensitized solar cells (p-DSSCs). The structural, electrical, and photovoltaic properties of the films as well as the devices were investigated by various techniques. The dye loading amount of the obtained film is 2.6 times that of the P25 electrodes. As revealed by electrochemical impedance spectroscopy results, the film derived from the as-prepared anatase TiO2 paste (A-TiO2) exhibits much smaller charge transport resistance and lower electron recombination rate than the P25 film, while the introduction of TiO2-sol into the paste can further remarkably decrease the resistance of the produced film (AS-TiO2). The p-DSSCs employing AS-TiO2 photoanode yield a high efficiency up to 7.51%, which is 86% higher than the P25 reference cells and also 31% higher than the A-TiO2 cell. As a proof of concept, the newly developed AS-TiO2 paste was also applied to low temperature processed perovskite solar cells (PSCs), and a promising high efficiency up to 9.95% was achieved. PMID- 26284588 TI - Suppression of Rituximab-resistant B-cell lymphoma with a novel multi-component anti-CD20 mAb nanocluster. AB - Although the anti-CD20 antibody Rituximab has revolutionized the treatment of Non Hodgkin Lymphoma (NHL), resistance to treatment still existed. Thus, strategies for suppressing Rituximab-resistant NHLs are urgently needed. Here, an anti-CD20 nanocluster (ACNC) is successfully constructed from its type I and type II mAb (Rituximab and 11B8). These distinct anti-CD20 mAbs are mass grafted to a short chain polymer (polyethylenimine). Compared with parental Rituximab and 11B8, the ACNC had a reduced "off-rate". Importantly, ACNC efficiently inhibited Rituximab resistant lymphomas in both disseminated and localized human NHL xenograft models. Further results revealed that ACNC is significantly potent in inducing caspase-dependent apoptosis and lysosome-mediated programmed cell death (PCD). This may help explain why ACNC is effective in suppressing rituximab-resistant lymphoma while Rituximab and 11B8 are not. Additionally, ACNC experienced low clearance from peripheral blood and high intratumor accumulation. This improved pharmacokinetics is attributed to the antibody-antigen reaction (active targeting) and enhanced permeability and retention (ERP) effect (passive targeting). This study suggested that ACNC might be a promising therapeutic agent for treatment of rituximab-resistant lymphomas. PMID- 26284589 TI - Knock out of the BASIGIN/CD147 chaperone of lactate/H+ symporters disproves its pro-tumour action via extracellular matrix metalloproteases (MMPs) induction. AB - BASIGIN/CD147/EMMPRIN is a multifunctional transmembrane glycoprotein strongly expressed in tumours. BASIGIN controls tumour metabolism, particularly glycolysis by facilitating lactic acid export through the two monocarboxylate transporters MCT1 and hypoxia-inducible MCT4. However, before being recognized as a co-carrier of MCTs, BASIGIN was described as an inducer of extracellular matrix metalloproteases (MMPs). Early on, a model emerged in which, tumour cells use the extracellular domain of BASIGIN to recognize and stimulate neighbouring fibroblasts to produce MMPs. However, this model has remained hypothetical since a direct link between BASIGIN and MMPs production has not yet been clearly established. To validate the BASIGIN/MMP hypothesis, we developed BASIGIN knockouts in three human tumour cell lines derived from glioma, colon, and lung adenocarcinoma. By using co-culture experiments of either human or mouse fibroblasts and tumour cell lines we showed, contrary to what has been abundantly published, that the disruption of BASIGIN in tumour cells and in MEFs has no action on the production of MMPs. Our findings do not support the notion that the pro-tumoural action of BASIGIN is mediated via induction of MMPs. Therefore, we propose that to date, the strongest pro-tumoural action of BASIGIN is mediated through the control of fermentative glycolysis. PMID- 26284592 TI - Autoimmune Hepatitis and Overlap Syndromes: Diagnosis and Management. PMID- 26284593 TI - Transition Zone Prostate-specific Antigen Density Could Better Guide the Rebiopsy Strategy in Men With Prostate Inflammation at Initial Biopsy. AB - OBJECTIVE: To assess the role of transition zone prostate-specific antigen density (TZPSAD) in determining rebiopsy strategy in men with prostate inflammation at initial biopsy. MATERIALS AND METHODS: Analysis was performed on data derived from transrectal ultrasound-guided prostate biopsy registry containing 2461 men who underwent biopsy between March 2005 and January 2015. Eligible patients were divided into 2 groups based on the presence of chronic inflammation in prostate. Group 1 consisted of 920 patients with histopathologic evidence of chronic inflammation and group 2 consisted of 1287 patients with no evidence of inflammation. Receiver operating characteristic curve analysis was performed to evaluate the accuracy of PSA, PSA density (PSAD), and TZPSAD for detecting prostate cancer (PCa) in each group. Patients who underwent rebiopsy during the study period were further assessed to determine factors that may predict the presence of PCa on subsequent biopsies. RESULTS: In group 1 patients, at 90% sensitivity for detecting PCa, PSAD and TZPSAD showed 19.7% and 37.8% specificity at cutoff values of 0.10 and 0.27 ng/mL/mL respectively, whereas in group 2 patients, PSAD and TZPSAD revealed 29.8% and 31.4% specificity, respectively. Chronic inflammation at initial biopsy was associated with a significant decrease in the likelihood of cancer detection during rebiopsy (odds ratio, 0.42; 95% confidence interval, 0.18-0.99). TZPSAD was found to be capable of sparing 39.8% of unnecessary rebiopsies in group 1 patients, whereas it spared 20.5% of unnecessary rebiopsies in group 2 patients. CONCLUSION: Applying TZPSAD is advantageous in determining rebiopsy strategy in patients with proven inflammation of prostate at initial biopsy. PMID- 26284594 TI - The Diagnosis of Benign Prostatic Obstruction: Validation of the Young Academic Urologist Clinical Nomogram. AB - OBJECTIVE: To externally validate the Young Academic Urologist (YAU) nomogram for the prediction of benign prostatic obstruction (BPO) in patients with lower urinary tract symptoms and benign prostatic enlargement. MATERIALS AND METHODS: Between January 2013 and September 2014, a consecutive series of patients with lower urinary tract symptoms and benign prostatic enlargement underwent standardized pressure flow studies (PFSs) in 2 tertiary Italian centers. Variables assessed were International Prostatic Symptom Score, Prostate Specific Antigen (PSA), prostate size, transitional zone volume, maximal urinary flow rate (Qmax), postvoid residual urine. BPO was defined as a Schafer grade >= 3 at PFSs. Qmax and transitional zone volume were plotted on the YAU nomogram to predict the presence of BPO. Receiver operating characteristic curve analysis was used to evaluate predictive properties of the nomogram for the final diagnosis of BPO. RESULTS: A total of 449 patients were consecutively enrolled. In those, 310 patients (69%) presented a BPO (Schafer >= 3) at PFSs. The novel YAU nomogram presented an area under the curve of 0.76; 95% confidence interval: 0.72-0.82 for the diagnosis of BPO. At the best cutoff value of 80% (nomogram probability), the sensitivity was 74% and specificity was 79%, the positive predictive value was 89%, and the negative predictive value was 56%. CONCLUSION: Although further studies are needed to confirm our results, the YAU nomogram was, in our experience, an excellent tool to predict the presence of BPO. PMID- 26284591 TI - Hepatocellular Carcinoma From Epidemiology to Prevention: Translating Knowledge into Practice. AB - The epidemiology of hepatocellular carcinoma (HCC) is characterized by dynamic temporal trends, several major established (i.e., HCV, HBV, alcohol) and emerging (i.e., diabetes, obesity, NAFLD) risk factors. Epidemiologic studies and clinical trials have identified additional demographic, clinical, pharmacological, genetic and life style factors that further affect or modify the likelihood of HCC and can be used in clinical practice to identify at-risk patients (i.e., risk stratification or prognostic algorithms) that can be targeted for prevention and early detection programs. These studies have also paved the way toward several well established preventive measures including HBV vaccination, HBV treatment, HCV treatment and HCC surveillance, and potential chemoprevention using statins, metformin or coffee. However, the effectiveness of HCC prevention in clinical practice and at the population level has lagged behind due to patient, provider, system, and societal factors. The Quality in the Continuum of Cancer Care model provides a framework for evaluating the HCC prevention processes, including potential failures that create a gap between efficacy and effectiveness. PMID- 26284595 TI - Male Urethral, Penile, and Incontinence Surgery: Is Resident Exposure Adequate? AB - OBJECTIVE: To evaluate trends in male urethral and penis/incontinence case volumes among urology residents and assess these for adequate surgical training/competency. METHODS: Accreditation Council for Graduate Medical Education (ACGME) case logs of urology residents graduating from U.S. programs from 2009 to 2013 were reviewed to determine the surgical volume of select index categories. Male urethral cases encompass urethrectomy and urethroplasty, whereas male penis/incontinence cases include urethral slings and sphincters. Case volumes as "surgeon," "assistant," and "teaching assistant" were reviewed and compared to ACGME minimum requirements. RESULTS: A total of 1032 graduating residents reported case logs. For male urethral surgery, residents reported weighted averages (standard deviation [SD]) of 12.7 (9.0) cases as "surgeon," 1.5 (3.5) cases as "assistant," and 0.2 (1.0) as "teaching assistant." The minimum requirement for these cases is 5. The annual 10th percentiles as "surgeon" ranged from 4 to 5 cases throughout the study period. For male penis/incontinence cases, residents reported weighted averages (SD) of 45.5 (22.7) cases as "surgeon," 3.6 (5.5) cases as "assistant," and 1.5 (3.0) cases as "teaching assistant." The minimum requirement is 10 cases. The 10th percentiles as "surgeon" ranged from 19 to 23 cases. CONCLUSION: Although the majority of residents met the minimum standard for these cases, about 10% of residents did not meet the requirement for male urethral surgery. In addition, a review of learning curves for these procedures suggests that the ACGME minimum requirements may be insufficient to confer actual competency in skill. Increasing this number in training or specialized postgraduate training programs is needed to provide actual competency. PMID- 26284596 TI - Passivity and Synchronization of Linearly Coupled Reaction-Diffusion Neural Networks With Adaptive Coupling. AB - In this paper, we study a general array model of coupled reaction-diffusion neural networks (NNs) with adaptive coupling. In order to ensure the passivity of the coupled reaction-diffusion neural networks, some adaptive strategies to tune the coupling strengths among network nodes are designed. By utilizing some inequality techniques and the designed adaptive laws, several sufficient conditions ensuring passivity are obtained. In addition, we reveal the relationship between passivity and synchronization of the coupled reaction diffusion NNs. Based on the obtained passivity results and the relationship between passivity and synchronization, a global synchronization criterion is established. Finally, numerical simulations are presented to illustrate the correctness and effectiveness of the proposed results. PMID- 26284598 TI - Sleep-related attentional bias in insomnia: A state-of-the-science review. AB - Prominent models of insomnia posit that sleep-related attentional bias plays an important role in the development and maintenance of insomnia. Here we conduct the first systematic review of the sleep-related attentional bias construct, indexed through reaction time-based experimental tasks. Literature search identified 13 studies that met pre-defined inclusion/exclusion criteria. Included studies involved between-group comparisons (poor sleepers versus controls), as well as sleep manipulations and correlational investigations with healthy sleepers. For studies involving comparisons between poor sleepers and healthy controls, effect size estimates were computed for task-relevant dependent variables. Six of the nine studies comparing poor sleepers and controls revealed statistically significant group differences in support of a differential sleep related attentional bias (medium-to-large effect sizes), with flicker, dot-probe and Posner tasks being most sensitive to group effects. Due to the paucity of studies and variability in design and measurement, no conclusions could be reached regarding manipulation or induction of attentional bias in good sleepers. Results from the relatively small number of studies support the presence of sleep related attentional bias in insomnia; however, its role in the development and/or maintenance of insomnia remains to be elucidated. We set out a research agenda aimed at advancing the understanding of sleep-related attention bias. PMID- 26284597 TI - Diagnostic and Prognostic Microbial Biomarkers in Inflammatory Bowel Diseases. AB - The microbiome plays multifaceted roles in the pathogenesis of inflammatory bowel diseases (IBD). Accordingly, the clinical challenge of patient heterogeneity in disease phenotype and response to treatment should in part be addressed by biomarkers that detect the host response to microbiota, and the levels of microbial taxa and products eliciting the host response in susceptible individuals. Molecular analysis has revealed much evidence for microbial taxonomic membership and microbial products in association with IBD, but their utility as clinical biomarkers is still in its infancy. A rich area of progress has been the development and validation of host serologic microbial biomarkers, which have achieved a distinctive position in the diagnosis and prognosis in IBD, and as a template for defining other categories of microbial biomarkers in disease state and phenotype. PMID- 26284600 TI - Diffusion MRI with Semi-Automated Segmentation Can Serve as a Restricted Predictive Biomarker of the Therapeutic Response of Liver Metastasis. AB - PURPOSE: To assess the value of semi-automated segmentation applied to diffusion MRI for predicting the therapeutic response of liver metastasis. METHODS: Conventional diffusion weighted magnetic resonance imaging (MRI) was performed using b-values of 0, 150, 300 and 450s/mm(2) at baseline and days 4, 11 and 39 following initiation of a new chemotherapy regimen in a pilot study with 18 women with 37 liver metastases from primary breast cancer. A semi-automated segmentation approach was used to identify liver metastases. Linear regression analysis was used to assess the relationship between baseline values of the apparent diffusion coefficient (ADC) and change in tumor size by day 39. RESULTS: A semi-automated segmentation scheme was critical for obtaining the most reliable ADC measurements. A statistically significant relationship between baseline ADC values and change in tumor size at day 39 was observed for minimally treated patients with metastatic liver lesions measuring 2-5cm in size (p=0.002), but not for heavily treated patients with the same tumor size range (p=0.29), or for tumors of smaller or larger sizes. ROC analysis identified a baseline threshold ADC value of 1.33MUm(2)/ms as 75% sensitive and 83% specific for identifying non responding metastases in minimally treated patients with 2-5cm liver lesions. CONCLUSION: Quantitative imaging can substantially benefit from a semi-automated segmentation scheme. Quantitative diffusion MRI results can be predictive of therapeutic outcome in selected patients with liver metastases, but not for all liver metastases, and therefore should be considered to be a restricted biomarker. PMID- 26284601 TI - Synthesis, characterization and application of ion imprinted polymeric nanobeads for highly selective preconcentration and spectrophotometric determination of Ni2+ ion in water samples. AB - Here, the researchers report on the synthesis of ion imprinted polymeric (IIP) nanoparticles using a thermal polymerization strategy, and their usage for the separation of Ni(2+) ion from water samples. The prepared Ni-IIP was characterized by colorimetry, FT-IR spectroscopy, and scanning electron microscopy. It was found that the particle size of the prepared particle to be 50 70 nm in diameter with the highly selective binding capability for Ni(2+) ion, with reasonable adsorption and desorption process. After preconcentration, bound ions can be eluted with an aqueous solution of hydrochloric acid, after their complexation with dimethylglyoxime, these ions can be quantified by UV-Vis absorption spectrophotometry. The effect of various parameters on the extraction efficiency including pH of sample solution, adsorption and leaching times, initial sample volume, concentration and volume of eluent were investigated. In selectivity study, it was found that imprinting causes increased affinity of the prepared IIP toward Ni(2+) ion over other ions such as Na(+), K(+), Ag(+), Co(2+), Cu(2+), Cd(2+), Hg(2+), Pb(2+), Zn(2+), Mn(2+), Mg(2+), Cr(3+), and Fe(3+). The prepared IIP can be used and regenerated for at least eight times without any significant decrease in binding affinities. The prepared IIP is considered to be promising and selective sorbent for solid-phase extraction and preconcentration of Ni(2+) ion from different water samples. PMID- 26284599 TI - Uterine overdistention induces preterm labor mediated by inflammation: observations in pregnant women and nonhuman primates. AB - OBJECTIVE: Uterine overdistention is thought to induce preterm labor in women with twin and multiple pregnancies, but the pathophysiology remains unclear. We investigated for the first time the pathogenesis of preterm birth associated with rapid uterine distention in a pregnant nonhuman primate model. STUDY DESIGN: A nonhuman primate model of uterine overdistention was created using preterm chronically catheterized pregnant pigtail macaques (Macaca nemestrina) by inflation of intraamniotic balloons (N = 6), which were compared to saline controls (N = 5). Cesarean delivery was performed due to preterm labor or at experimental end. Microarray, quantitative reverse transcriptase polymerase chain reaction, Luminex (Austin, TX), and enzyme-linked immunosorbent assay were used to measure messenger RNA (mRNA) and/or protein levels from monkey (amniotic fluid, myometrium, maternal plasma) and human (amniocytes, amnion, myometrium) tissues. Statistical analysis employed analysis of covariance and Wilcoxon rank sum. Biomechanical forces were calculated using the law of Laplace. RESULTS: Preterm labor occurred in 3 of 6 animals after balloon inflation and correlated with greater balloon volume and uterine wall stress. Significant elevations of inflammatory cytokines and prostaglandins occurred following uterine overdistention in an "inflammatory pulse" that correlated with preterm labor (interleukin [IL]-1beta, tumor necrosis factor [TNF]-alpha, IL-6, IL-8, CCL2, prostaglandin E2, prostaglandin F2alpha, all P < .05). A similar inflammatory response was observed in amniocytes in vitro following mechanical stretch (IL1beta, IL6, and IL8 mRNA multiple time points, P < .05), in amnion of women with polyhydramnios (IL6 and TNF mRNA, P < .05) and in amnion (TNF-alpha) and myometrium of women with twins in early labor (IL6, IL8, CCL2, all P < .05). Genes differentially expressed in the nonhuman primate after balloon inflation and in women with polyhydramnios and twins are involved in tissue remodeling and muscle growth. CONCLUSION: Uterine overdistention by inflation of an intraamniotic balloon is associated with an inflammatory pulse that precedes and correlates with preterm labor. Our results indicate that inflammation is an early event after a mechanical stress on the uterus and leads to preterm labor when the stress is sufficiently great. Further, we find evidence of uterine tissue remodeling and muscle growth as a common, perhaps compensatory, response to uterine distension. PMID- 26284604 TI - Sterically Controlled Pd-Catalyzed Chemoselective Ketone Synthesis via N-C Cleavage in Twisted Amides. AB - Highly chemoselective, palladium(0)-catalyzed, direct cross-coupling between boronic acids and geometrically activated amides is reported. The reaction proceeds via selective activation of the N-C(O) bond, shows excellent functional group tolerance, and delivers the versatile ketone products in high yields. The observed reactivity is consistent with a decrease of nN -> pi*C?O conjugation resulting from destabilization of the amide ground state. Notably, the method provides direct access to acyl-metal intermediates from sterically distorted, bench-stable amide precursors under mild catalytic conditions. PMID- 26284605 TI - Volitional Initiation and Fast Visuomotor Networks: Why Movements are Slow to Start and Quick to Correct. PMID- 26284603 TI - Intrinsic sequence specificity of the Cas1 integrase directs new spacer acquisition. AB - The adaptive prokaryotic immune system CRISPR-Cas provides RNA-mediated protection from invading genetic elements. The fundamental basis of the system is the ability to capture small pieces of foreign DNA for incorporation into the genome at the CRISPR locus, a process known as Adaptation, which is dependent on the Cas1 and Cas2 proteins. We demonstrate that Cas1 catalyses an efficient trans esterification reaction on branched DNA substrates, which represents the reverse- or disintegration reaction. Cas1 from both Escherichia coli and Sulfolobus solfataricus display sequence specific activity, with a clear preference for the nucleotides flanking the integration site at the leader-repeat 1 boundary of the CRISPR locus. Cas2 is not required for this activity and does not influence the specificity. This suggests that the inherent sequence specificity of Cas1 is a major determinant of the adaptation process. PMID- 26284602 TI - A central role for the retrosplenial cortex in de novo environmental learning. AB - With experience we become accustomed to the types of environments that we normally encounter as we navigate in the world. But how does this fundamental knowledge develop in the first place and what brain regions are involved? To examine de novo environmental learning, we created an 'alien' virtual reality world populated with landmarks of which participants had no prior experience. They learned about this environment by moving within it during functional MRI (fMRI) scanning while we tracked their evolving knowledge. Retrosplenial cortex (RSC) played a central and highly selective role by representing only the most stable, permanent features in this world. Subsequently, increased coupling was noted between RSC and hippocampus, with hippocampus then expressing knowledge of permanent landmark locations and overall environmental layout. Studying how environmental representations emerge from scratch provided a new window into the information processing underpinning the brain's navigation system, highlighting the key influence of the RSC. PMID- 26284606 TI - Synergistic Effects of Doping and Thermal Treatment on Organic Semiconducting Nanowires. AB - Doping of small molecular donors or acceptors on conjugated organic materials can be used to improve the performance of organic electronics. Here we demonstrate highly aligned poly(3-hexylthiophene) (P3HT) nanowires (NWs) doped with 2,3,5,6 tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4-TCNQ) using electrohydrodynamic organic NW printing. The transistor based on p-doped NWs had an order of magnitude higher mobility than did the undoped NW device. This significant improvement resulted from the synergistic effects of p-type doping and thermal annealing on F4-TCNQ-doped P3HT NWs, which induce microstructure changes in P3HT chains. PMID- 26284607 TI - Highly Efficient Flexible Perovskite Solar Cells with Antireflection and Self Cleaning Nanostructures. AB - Flexible thin film solar cells have attracted a great deal of attention as mobile power sources and key components for building-integrated photovoltaics, due to their light weight and flexible features in addition to compatibility with low cost roll-to-roll fabrication processes. Among many thin film materials, organometallic perovskite materials are emerging as highly promising candidates for high efficiency thin film photovoltaics; however, the performance, scalability, and reliability of the flexible perovskite solar cells still have large room to improve. Herein, we report highly efficient, flexible perovskite solar cells fabricated on ultrathin flexible glasses. In such a device structure, the flexible glass substrate is highly transparent and robust, with low thermal expansion coefficient, and perovskite thin film was deposited with a thermal evaporation method that showed large-scale uniformity. In addition, a nanocone array antireflection film was attached to the front side of the glass substrate in order to improve the optical transmittance and to achieve a water-repelling effect at the same time. It was found that the fabricated solar cells have reasonable bendability, with 96% of the initial value remaining after 200 bending cycles, and the power conversion efficiency was improved from 12.06 to 13.14% by using the antireflection film, which also demonstrated excellent superhydrophobicity. PMID- 26284608 TI - Conjugation of Ciprofloxacin with Poly(2-oxazoline)s and Polyethylene Glycol via End Groups. AB - The antibiotic ciprofloxacin (CIP) was covalently attached to the chain end of poly(2-methyloxazoline) (PMOx), poly(2-ethyloxazoline) (PEtOx), and polyethylene glycol (PEG), and the antimicrobial activity of these conjugates was tested for Staphylococcus aureus, Streptococcus mutans, Escherichia coli, Pseudomonas aeruginosa, and Kleisella pneumoniae. Chemical structures of the conjugates were proven by (1)H NMR and electron spray ionization mass spectrometry. The direct coupling of PMOx and CIP resulted in low antimicrobial activity. The coupling via a spacer afforded molecular weight dependent activity with a molar minimal inhibitory concentration that is even higher than that of the pristine CIP. The antimicrobial activity of the conjugates increases in the order of PMOx < PEtOx < PEG. Conjugation of CIP and a quaternary ammonium compound via PMOx did not result in higher activity, indicating no satellite group or synergistic effect of the different biocidal end groups. PMID- 26284609 TI - Breath Figure: A Nature-Inspired Preparation Method for Ordered Porous Films. PMID- 26284611 TI - Increase in Multistate Foodborne Disease Outbreaks-United States, 1973-2010. AB - INTRODUCTION: Changes in food production and distribution have increased opportunities for foods contaminated early in the supply chain to be distributed widely, increasing the possibility of multistate outbreaks. In recent decades, surveillance systems for foodborne disease have been improved, allowing officials to more effectively identify related cases and to trace and identify an outbreak's source. MATERIALS AND METHODS: We reviewed multistate foodborne disease outbreaks reported to the Centers for Disease Control and Prevention's Foodborne Disease Outbreak Surveillance System during 1973-2010. We calculated the percentage of multistate foodborne disease outbreaks relative to all foodborne disease outbreaks and described characteristics of multistate outbreaks, including the etiologic agents and implicated foods. RESULTS: Multistate outbreaks accounted for 234 (0.8%) of 27,755 foodborne disease outbreaks, 24,003 (3%) of 700,600 outbreak-associated illnesses, 2839 (10%) of 29,756 outbreak-associated hospitalizations, and 99 (16%) of 628 outbreak associated deaths. The median annual number of multistate outbreaks increased from 2.5 during 1973-1980 to 13.5 during 2001-2010; the number of multistate outbreak-associated illnesses, hospitalizations, and deaths also increased. Most multistate outbreaks were caused by Salmonella (47%) and Shiga toxin-producing Escherichia coli (26%). Foods most commonly implicated were beef (22%), fruits (13%), and leafy vegetables (13%). CONCLUSIONS: The number of identified and reported multistate foodborne disease outbreaks has increased. Improvements in detection, investigation, and reporting of foodborne disease outbreaks help explain the increasing number of reported multistate outbreaks and the increasing percentage of outbreaks that were multistate. Knowing the etiologic agents and foods responsible for multistate outbreaks can help to identify sources of food contamination so that the safety of the food supply can be improved. PMID- 26284610 TI - Glycolytic Reprogramming in Myofibroblast Differentiation and Lung Fibrosis. AB - RATIONALE: Dysregulation of cellular metabolism has been shown to participate in several pathologic processes. However, the role of metabolic reprogramming is not well appreciated in the pathogenesis of organ fibrosis. OBJECTIVES: To determine if glycolytic reprogramming participates in the pathogenesis of lung fibrosis and assess the therapeutic potential of glycolytic inhibition in treating lung fibrosis. METHODS: A cell metabolism assay was performed to determine glycolytic flux and mitochondrial respiration. Lactate levels were measured to assess glycolysis in fibroblasts and lungs. Glycolytic inhibition by genetic and pharmacologic approaches was used to demonstrate the critical role of glycolysis in lung fibrosis. MEASUREMENTS AND MAIN RESULTS: Augmentation of glycolysis is an early and sustained event during myofibroblast differentiation, which is dependent on the increased expression of critical glycolytic enzymes, in particular, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). Augmented glycolysis contributes to the stabilization of hypoxia-inducible factor 1-alpha, a master regulator of glycolytic enzymes implicated in organ fibrosis, by increasing cellular levels of tricarboxylic acid cycle intermediate succinate in lung myofibroblasts. Inhibition of glycolysis by the PFKFB3 inhibitor 3PO or genomic disruption of the PFKFB3 gene blunted the differentiation of lung fibroblasts into myofibroblasts, and attenuated profibrotic phenotypes in myofibroblasts isolated from the lungs of patients with idiopathic pulmonary fibrosis. Inhibition of glycolysis by 3PO demonstrates therapeutic benefit in bleomycin-induced and transforming growth factor-beta1-induced lung fibrosis in mice. CONCLUSIONS: Our data support the novel concept of glycolytic reprogramming in the pathogenesis of lung fibrosis and provide proof-of-concept that targeting this pathway may be efficacious in treating fibrotic disorders, such as idiopathic pulmonary fibrosis. PMID- 26284613 TI - In vitro and in vivo comparison of the biological activities of two traditionally and widely used Arum species from Jordan: Arum dioscoridis Sibth & Sm. and Arum palaestinum Boiss. AB - Arum dioscoridis and A. palaestinum (Araceae) are indigenous plant species in Jordan. HPLC-MS analysis of A. dioscoridis revealed the presence of apigenin, luteolin, quercetin, quercetin-3-O-beta-glucoside, vitexin, isoorientin, esculin, and caffeic and ferulic acids. Both Arum spp., influenced gastrointestinal carbohydrate and lipid digestion and absorption. Orlistat inhibited dose dependently and highly substantially pancreatic lipase (PL) in vitro. Similar to orlistat, Arum species aqueous extracts (AEs), apigenin, caffeic acid and esculin exhibited a concentration related PL inhibition. Comparable to acarbose, dual inhibition of alpha-amylase/alpha-glucosidase was observed for both Arum species. Like guar gum, A. dioscoridis AE minimised substantially area under 24 h glucose curve. Acute starch-induced postprandial hyperglycaemia in overnight fasting rats was highly significantly (p < 0.001) decreased by A. dioscoridis AE. A. palaestinum could not perform effectively in either starch- or glucose-fed fasting rats. No antiproliferative effects against colorectal cancer cell lines HT29, HCT116 and SW620 were detected for tested Arum spp. PMID- 26284612 TI - Phase 1 trial of carfilzomib (PR-171) in combination with vorinostat (SAHA) in patients with relapsed or refractory B-cell lymphomas. AB - A phase 1 study with carfilzomib and vorinostat was conducted in 20 B-cell lymphoma patients. Vorinostat was given orally twice daily on days 1, 2, 3, 8, 9, 10, 15, 16, and 17 followed by carfilzomib (given as a 30-min infusion) on days 1, 2, 8, 9, 15, and 16. A treatment cycle was 28 days. Dose escalation initially followed a standard 3 + 3 design, but adapted a more conservative accrual rule following dose de-escalation. The maximum tolerated dose was 20 mg/m2 carfilzomib and 100 mg vorinostat (twice daily). The dose-limiting toxicities were grade 3 pneumonitis, hyponatremia, and febrile neutropenia. One patient had a partial response and two patients had stable disease. Correlative studies showed a decrease in NF-kappaB activation and an increase in Bim levels in some patients, but these changes did not correlate with clinical response. PMID- 26284614 TI - Transforming exoelectrogens for biotechnology using synthetic biology. AB - Extracellular electron transfer pathways allow certain bacteria to transfer energy between intracellular chemical energy stores and extracellular solids through redox reactions. Microorganisms containing these pathways, exoelectrogens, are a critical part of microbial electrochemical technologies that aim to impact applications in bioenergy, biosensing, and biocomputing. However, there are not yet any examples of economically viable microbial electrochemical technologies due to the limitations of naturally occurring exoelectrogens. Here we first briefly summarize recent discoveries in understanding extracellular electron transfer pathways, then review in-depth the creation of customized and novel exoelectrogens for biotechnological applications. We analyze engineering efforts to increase current production in native exoelectrogens, which reveals that modulating certain processes within extracellular electron transfer are more effective than others. We also review efforts to create new exoelectrogens and highlight common challenges in this work. Lastly, we summarize work utilizing engineered exoelectrogens for biotechnological applications and the key obstacles to their future development. Fueled by the development of genetic tools, these approaches will continue to expand and genetically modified organisms will continue to improve the outlook for microbial electrochemical technologies. PMID- 26284615 TI - Memory conjunction clusters: Influence of familiarity and recollection. AB - In the memory conjunction paradigm, the number of times that constituents of conjunction lures were studied and the method of presentation were varied. In two experiments, participants were presented with eight parent items that could be recombined at test to form a conjunction lure. The constituents that were shared between the parent items and the conjunction lures were either presented in the same words (e.g., blackmail and jailbird presented four times each for the conjunction lure blackbird) or in different words (e.g., the targets footstool, footlocker, foothill, footbridge, baseball, softball, basketball, and golfball for the conjunction lure football). In both experiments, rates of false recognition were higher in the Different condition as opposed to the Same condition. These results provide evidence that participants in the Same condition were able to utilise a recall-to-reject strategy by remembering the repeatedly presented parent word. In the Different condition, participants were not able to utilise that strategy and instead relied on the familiarity of the repeatedly presented constituents which led to higher rates of false recognition. PMID- 26284616 TI - Intractable Tangles in the Bird Family Tree. AB - Rapid sequential speciation events can outpace the fixation of genetic variants, resulting in a family tree that lacks clear branching patterns. A new study of bird genomes reveals such an explosive super-radiation that may coincide with the mass extinction at the end of the Cretaceous period. PMID- 26284617 TI - Stakeholders' Perceptions on Shortage of Healthcare Workers in Primary Healthcare in Botswana: Focus Group Discussions. AB - BACKGROUND: An adequate health workforce force is central to universal health coverage and positive public health outcomes. However many African countries have critical shortages of healthcare workers, which are worse in primary healthcare. The aim of this study was to explore the perceptions of healthcare workers, policy makers and the community on the shortage of healthcare workers in Botswana. METHOD: Fifteen focus group discussions were conducted with three groups of policy makers, six groups of healthcare workers and six groups of community members in rural, urban and remote rural health districts of Botswana. All the participants were 18 years and older. Recruitment was purposive and the framework method was used to inductively analyse the data. RESULTS: There was a perceived shortage of healthcare workers in primary healthcare, which was believed to result from an increased need for health services, inequitable distribution of healthcare workers, migration and too few such workers being trained. Migration was mainly the result of unfavourable personal and family factors, weak and ineffective healthcare and human resources management, low salaries and inadequate incentives for rural and remote area service. CONCLUSIONS: Botswana has a perceived shortage of healthcare workers, which is worse in primary healthcare and rural areas, as a result of multiple complex factors. To address the scarcity the country should train adequate numbers of healthcare workers and distribute them equitably to sufficiently resourced healthcare facilities. They should be competently managed and adequately remunerated and the living conditions and rural infrastructure should also be improved. PMID- 26284618 TI - Butterfly Density and Behaviour in Uncut Hay Meadow Strips: Behavioural Ecological Consequences of an Agri-Environmental Scheme. AB - Sparing zones from mowing has been proposed, and applied, to improve local conditions for survival and reproduction of insects in hay meadows. However, little is known about the efficiency of refuge zones and the consequences for local populations. We studied population densities of butterflies before and after mowing in the refuge zone of 15 meadows in 2009 and 2011. We also studied the behaviour of the meadow brown (Maniola jurtina) comparing nectar use, interactions and flights in the refuge zone before and after mowing. Densities of grassland butterflies in this zone doubled on average after mowing. The density of females of M. jurtina increased on average fourfold, while males showed a more modest increase. In line with the idea of increased scramble competition in the refuge zone after mowing, M. jurtina increased the time spent on nectar feeding, the preferred nectar source was visited more frequently, and females made more use of non-preferred nectar sources. Maniola jurtina did not interact more with conspecifics after mowing, but interactions lasted longer. Flight tracks did not change in linearity, but were faster and shorter after mowing. After mowing, only a part of the local grassland butterflies moved to the uncut refuge zone. The resulting concentration effect alters the time allocated to different activities, nectar use and movements. These aspects have been largely ignored for agri environmental schemes and grassland management in nature reserves and raise questions about optimal quantities and quality of uncut refuge sites for efficient conservation of grassland arthropods in agricultural landscapes. PMID- 26284619 TI - Dexamethasone-Mediated Activation of Fibronectin Matrix Assembly Reduces Dispersal of Primary Human Glioblastoma Cells. AB - Despite resection and adjuvant therapy, the 5-year survival for patients with Glioblastoma multiforme (GBM) is less than 10%. This poor outcome is largely attributed to rapid tumor growth and early dispersal of cells, factors that contribute to a high recurrence rate and poor prognosis. An understanding of the cellular and molecular machinery that drive growth and dispersal is essential if we are to impact long-term survival. Our previous studies utilizing a series of immortalized GBM cell lines established a functional causation between activation of fibronectin matrix assembly (FNMA), increased tumor cohesion, and decreased dispersal. Activation of FNMA was accomplished by treatment with Dexamethasone (Dex), a drug routinely used to treat brain tumor related edema. Here, we utilize a broad range of qualitative and quantitative assays and the use of a human GBM tissue microarray and freshly-isolated primary human GBM cells grown both as conventional 2D cultures and as 3D spheroids to explore the role of Dex and FNMA in modulating various parameters that can significantly influence tumor cell dispersal. We show that the expression and processing of fibronectin in a human GBM tissue-microarray is variable, with 90% of tumors displaying some abnormality or lack in capacity to secrete fibronectin or assemble it into a matrix. We also show that low-passage primary GBM cells vary in their capacity for FNMA and that Dex treatment reactivates this process. Activation of FNMA effectively "glues" cells together and prevents cells from detaching from the primary mass. Dex treatment also significantly increases the strength of cell-ECM adhesion and decreases motility. The combination of increased cohesion and decreased motility discourages in vitro and ex vivo dispersal. By increasing cell-cell cohesion, Dex also decreases growth rate of 3D spheroids. These effects could all be reversed by an inhibitor of FNMA and by the glucocorticoid receptor antagonist, RU-486. Our results describe a new role for Dex as a suppressor of GBM dispersal and growth. PMID- 26284621 TI - Predicting Outcome With Diffusion-Weighted Imaging in Cardiac Arrest Patients Receiving Hypothermia Therapy: Multicenter Retrospective Cohort Study. AB - OBJECTIVES: Many comatose patients following cardiac arrest have ischemic brain injury. Diffusion-weighted imaging is a sensitive tool to identify hypoxic ischemic brain injury. The accurate prediction of the prognosis for comatose cardiac arrest survivors has been challenging, and thus, a multimodal approach, combining diffusion-weighted image findings, could be feasible. The aim of this study was to assess regional brain injury on diffusion-weighted imaging and to test the potential association with its neurologic outcome in patients treated with target temperature management after out-of-hospital cardiac arrest. DESIGN AND SETTING: A multicenter, registry-based, retrospective cohort study was conducted using cases from 24 hospitals across South Korea. Of the 930 adult (>=18 yr) nontraumatic out-of-hospital cardiac arrest patients treated with target temperature management between January 2007 and December 2012 at these hospitals, we included the patients who underwent brain diffusion-weighted imaging in the first week after cardiac arrest. The brain regions examined included the four cerebral lobes, basal ganglia-thalamus, brain stem, and cerebellum. Imaging results were compared between a good neurologic outcome, defined as a cerebral performance category score of 1 or 2, and a poor neurologic outcome (cerebral performance category score>=3). MEASUREMENT AND MAIN RESULTS: Poor neurologic outcome occurred in 118 of the 172 patients analyzed (68.6%). Positive diffusion-weighted image findings, defined as any regional brain injury lesion in diffusion-weighted imaging, were present in 106 patients. Positive diffusion-weighted image findings had 93% sensitivity, 86% specificity, 76% positive predictive value, and 96% negative predictive value for a poor neurologic outcome. The poor outcome group had higher numbers of affected brain lesions than the good outcome group (3.8+/-1.9 vs 0.1+/-0.6; p<0.01). By multivariate analysis, positive diffusion-weighted image findings (odds ratio, 58.2; 95% CI, 13.29-254.91) and lack of a shockable rhythm (odds ratio, 0.13; 95% CI, 0.03-0.57) were associated with a poor neurologic outcome. CONCLUSIONS: Diffusion-weighted imaging allows reliable prediction of poor neurologic outcome in comatose patients treated with target temperature management after out-of hospital cardiac arrest. Further prospective validation study will be required to generalize this result. PMID- 26284620 TI - DMD Mutations in 576 Dystrophinopathy Families: A Step Forward in Genotype Phenotype Correlations. AB - Recent advances in molecular therapies for Duchenne muscular dystrophy (DMD) require precise genetic diagnosis because most therapeutic strategies are mutation-specific. To understand more about the genotype-phenotype correlations of the DMD gene we performed a comprehensive analysis of the DMD mutational spectrum in a large series of families. Here we provide the clinical, pathological and genetic features of 576 dystrophinopathy patients. DMD gene analysis was performed using the MLPA technique and whole gene sequencing in blood DNA and muscle cDNA. The impact of the DNA variants on mRNA splicing and protein functionality was evaluated by in silico analysis using computational algorithms. DMD mutations were detected in 576 unrelated dystrophinopathy families by combining the analysis of exonic copies and the analysis of small mutations. We found that 471 of these mutations were large intragenic rearrangements. Of these, 406 (70.5%) were exonic deletions, 64 (11.1%) were exonic duplications, and one was a deletion/duplication complex rearrangement (0.2%). Small mutations were identified in 105 cases (18.2%), most being nonsense/frameshift types (75.2%). Mutations in splice sites, however, were relatively frequent (20%). In total, 276 mutations were identified, 85 of which have not been previously described. The diagnostic algorithm used proved to be accurate for the molecular diagnosis of dystrophinopathies. The reading frame rule was fulfilled in 90.4% of DMD patients and in 82.4% of Becker muscular dystrophy patients (BMD), with significant differences between the mutation types. We found that 58% of DMD patients would be included in single exon-exon skipping trials, 63% from strategies directed against multiexon-skipping exons 45 to 55, and 14% from PTC therapy. A detailed analysis of missense mutations provided valuable information about their impact on the protein structure. PMID- 26284623 TI - Direct Dating and Physico-Chemical Analyses Cast Doubts on the Coexistence of Humans and Dwarf Hippos in Cyprus. AB - In the Mediterranean, the island dwarf megafaunas became extinct around the end of the Pleistocene, during a period of rapid and global climate change. In Cyprus, this coincided with the first human presence on the island, as attested by the rock shelter of Akrotiri-Aetokremnos where an Epipaleolithic anthropogenic layer (stratum 2) was found overlying a massive accumulation of pygmy hippopotamus (Phanourios minor (Desmarest, 1822)) [Boekschoten and Sondaar, 1972] bones (stratum 4). The relationship between the two layers is highly controversial and the role played by humans in hippo extinction remains fiercely debated. Here, we provide new, direct radiocarbon and physico-chemical analyses on calcined bones which elucidates the complex depositional history of the assemblage. Bone turquoise was identified using micro-PIXE analysis and depth profiling together with Vis spectroscopy, demonstrating that these bones were not freshly burned. Bayesian modeling of the radiocarbon dates indicates that stratum 4 accumulated during the first half of the 13th mill cal BP and that calcination occurred several hundred years later. We conclude that accumulation occurred naturally during the beginning of the Younger Dryas and that Epipalaeolithic visitors subsequently used the bones as fuel, starting from the mid-13th mill cal BP. At that time, dwarf hippos were probably already extinct or at least highly endangered. Our results shed new light on the possible causes of hippo extinction, on the subsequent introduction of the wild boar and on the earliest occupation of the island by humans. PMID- 26284622 TI - Dynein Heavy Chain, Encoded by Two Genes in Agaricomycetes, Is Required for Nuclear Migration in Schizophyllum commune. AB - The white-rot fungus Schizophyllum commune (Agaricomycetes) was used to study the cell biology of microtubular trafficking during mating interactions, when the two partners exchange nuclei, which are transported along microtubule tracks. For this transport activity, the motor protein dynein is required. In S. commune, the dynein heavy chain is encoded in two parts by two separate genes, dhc1 and dhc2. The N-terminal protein Dhc1 supplies the dimerization domain, while Dhc2 encodes the motor machinery and the microtubule binding domain. This split motor protein is unique to Basidiomycota, where three different sequence patterns suggest independent split events during evolution. To investigate the function of the dynein heavy chain, the gene dhc1 and the motor domain in dhc2 were deleted. Both resulting mutants were viable, but revealed phenotypes in hyphal growth morphology and mating behavior as well as in sexual development. Viability of strain Deltadhc2 is due to the higher expression of kinesin-2 and kinesin-14, which was proven via RNA sequencing. PMID- 26284624 TI - Destabilization of the Quaternary Structure of Bovine Heart Cytochrome c Oxidase upon Removal of Tightly Bound Cardiolipin. AB - The quaternary structural stability of cardiolipin-containing (CcO(CL+)) versus CL-free cytochrome c oxidase (CcO(CL-)) was compared using structural perturbants as probes. Exposure to increasing concentrations of urea or guanidinium chloride causes sequential dissociation of five subunits from CcO(CL+) in the order VIa and VIb, followed by III and VIIa, and ultimately Vb. Removal of CL from CcO destabilizes the association of each of these five subunits with the core of CcO. Subunits VIa and VIb spontaneously dissociate from CcO(CL-) even in the absence of denaturant and are no longer present after purification of the CL-free 11 subunit complex by ion exchange chromatography. The other 11 subunits remain associated in a partially active complex, but the association of subunits III, VIIa, and Vb is weakened; i.e., the midpoints for the subunit dissociation curves are each shifted to a lower perturbant concentration (lower by 1.1-1.7 M urea; lower by 0.3-0.4 M GdmCl). This corresponds to a decrease of ~9 kJ in the Gibbs free association energy for each of these subunits when CL is removed from CcO. With either CcO(CL+) or CcO(CL-), loss of enzymatic activity occurs coincident with dissociation of subunits III and VIIa. The loss of activity is irreversible, and reactivation of CcO(CL-) by exogenous CL occurs only if both subunits remain associated with the core of CcO. Inclusion of sulfate anions stabilizes the association of VIIa more than III, resulting in a slight separation of the urea induced dissociation curves. In this case, activity loss correlates much better with dissociation of subunit VIIa than III. We conclude that (1) bound cardiolipin is an important stabilizing factor in the quaternary structure of CcO and (2) association of subunit VIIa (possibly together with subunit III) is critical for functional CL binding and full electron-transfer activity of CcO. PMID- 26284626 TI - Buckled diamond-like carbon nanomechanical resonators. AB - We have developed capacitively-transduced nanomechanical resonators using sp(2) rich diamond-like carbon (DLC) thin films as conducting membranes. The electrically conducting DLC films were grown by physical vapor deposition at a temperature of 500 degrees C. Characterizing the resonant response, we find a larger than expected frequency tuning that we attribute to the membrane being buckled upwards, away from the bottom electrode. The possibility of using buckled resonators to increase frequency tuning can be of advantage in rf applications such as tunable GHz filters and voltage-controlled oscillators. PMID- 26284627 TI - Use of Air Transport for Minor Burns: Is There Room for Improvement? AB - Since 1981, the number of US burn centers has decreased by 29%, resulting in more long distance referrals to remaining facilities. Air transport is often the only feasible method for remote patients to reach few remaining burn centers. A significant proportion of flown-in patients have minor burns and are discharged within 24 hours, representing potential over-utilization of resources with increased cost to the healthcare system for no perceptible benefit. We explored factors associated with air transport of burns and opportunities for system improvement. Retrospective review of burn patients transferred by air to regional burn center between January 2003 and June 2013. Demographic, injury and clinical outcome data were acquired from the institutional Burn Registry. Minor burns constituted 17.7% of all flown admits (236/1331). Children were more likely to be included in this cohort at 32% vs 21.6% of adults (P = .0004). The overtriaged cohort had significantly lower % total BSA than accurately triaged cohort (3.3% vs 15%; P = .0001). Subjects with electrical burn injury were twice as likely to be overtriaged than accurately triaged (10.6% vs 5%; P = .002). The average % total BSA in the overtriaged group was 3.3%; the face was most common area burned (47.7%). The average estimate of charges for transfer was between $25,000 and 30,000/patient. The incidence of overtriage among flown-in burn patients, approximately 20%, represents substantial unnecessary healthcare expenditure. Improved burn care education, incentives to increase use of telemedicine, and modification of American Burn Association guidelines to include consultation with a burn center rather than automatic transfer are needed to reduce this cost to the healthcare system. PMID- 26284625 TI - Phloroglucinol Attenuates the Cognitive Deficits of the 5XFAD Mouse Model of Alzheimer's Disease. AB - Alzheimer's disease (AD) is the most common form of dementia among the elderly. Neuritic plaques whose primary component is amyloid beta peptide (Abeta) and neurofibrillary tangles which are composed of hyperphosphorylated tau, are known to be the neuropathological hallmarks of AD. In addition, impaired synaptic plasticity in neuronal networks is thought to be important mechanism underlying for the cognitive deficits observed in AD. Although various causative factors, including excitotoxicity, mitochondrial dysregulation and oxidative damage caused by Abeta, are involved in early onset of AD, fundamental therapeutics that can modify the progression of this disease are not currently available. In the present study, we investigated whether phloroglucinol (1, 3, 5 trihydroxybenzene), a component of phlorotannins, which are plentiful in Ecklonia cava, a marine brown alga species, displays therapeutic activities in AD. We found that phloroglucinol attenuates the increase in reactive oxygen species (ROS) accumulation induced by oligomeric Abeta1-42 (Abeta1-42) treatment in HT 22, hippocampal cell line. In addition, phloroglucinol was shown to ameliorate the reduction in dendritic spine density induced by Abeta1-42 treatment in rat primary hippocampal neuron cultures. We also found that the administration of phloroglucinol to the hippocampal region attenuated the impairments in cognitive dysfunction observed in 22-week-old 5XFAD (Tg6799) mice, which are used as an AD animal model. These results indicate that phloroglucinol displays therapeutic potential for AD by reducing the cellular ROS levels. PMID- 26284628 TI - A Case of Argyria and Acute Leukopenia Associated with the Use of an Antimicrobial Soft Silicone Foam Dressing. AB - Silver has had an important role in preventing burn-related infections for decades. Relatively few side effects is one factor that has led to its wide spread use. Here, the authors present the first case of argyria, acute leukopenia, and possibly acute kidney injury associated with the use of a silver containing soft silicone foam dressing. A 56-year-old female was transferred to the burn center with an exfoliating skin condition involving 70% TBSA diagnosed as toxic epidermal necrolysis associated with trimethoprim/sulfamethoxazole. On presentation she appeared to have clinical sepsis and was started on vancomycin and piperacillin/tazobactam. Clinical sepsis resolved within several days. Initial wound care consisted of daily topical double antibiotic and 3% bismuth tribromophenate petroleum gauze. After several days, the wounds were covered with a silver-containing soft silicone foam dressing. After 7 days, the leukocyte count declined from 18,000 to 600/cm. Silver toxicity was suspected and the dressings removed. Initial serum silver level was 190 and 249 MUg/L 1 week later. The leukocyte level normalized within 7 days. Over the following days and weeks, the patient's skin began to show blue-gray coloration consistent with argyria. The patient subsequently developed acute kidney injury requiring hemodialysis and multiple organ failure. Although controversy exists about the causal relationship between silver-containing dressings and leukopenia, the authors believe that this case represents a case of acute leukopenia and argyria from the use of a silver containing soft silicone foam dressing. It may have been a contributing factor to the development of acute kidney injury as well. PMID- 26284629 TI - Pediatric Frostbite Treated by Negative Pressure Wound Therapy. AB - Frostbite injury in children can lead to abnormal growth and premature fusion of the epiphyseal cartilage with long-term sequela including, but not limited to, arthroses, deformity, and amputation of the phalanges. This was a retrospective chart review of pediatric frostbite identified in an in-house burn center registry from March 1999 to March 2014. Therapeutic management included negative pressure wound therapy (NPWT). Three patients (age 16-31 months) had frostbitten hands because they were outside in cold weather without gloves. They presented within 24 hours after injury, underwent 5-6 days of NPWT after excision of blisters, and did not lose the distal portion of their digits, or require amputations. On follow-up, all hands were healed well with only minimal or no effect on the growth plate of these pediatric patients. In the early period after frostbite, NPWT may be beneficial in preserving the epiphyseal cartilage in children and preventing long-term complications. PMID- 26284630 TI - Geographic Mapping as a Tool for Identifying Communities at High Risk for Fires. AB - The purpose of this study was to evaluate whether the sample of older adults in a home fire safety (HFS) study captured participants living in the areas at highest risk for fire occurrence. The secondary aim was to identify high risk areas to focus future HFS interventions. Geographic information systems software was used to identify census tracts where study participants resided. Census data for these tracts were compared with participant data based on seven risk factors (ie, age greater than 65 years, nonwhite race, below high school education, low socioeconomic status, rented housing, year home built, home value) previously identified in a fire risk model. The distribution of participants and census tracts among risk categories determined how well higher risk census tracts were sampled. Of the 46 census tracts where the HFS intervention was implemented, 78% (n = 36) were identified as high or severe risk according to the fire risk model. Study participants' means for median annual family income (P < .0001) and median home value (P < .0001) were significantly lower than the census tract means (n = 46), indicating participants were at higher risk of fire occurrence. Of the 92 census tracts identified as high or severe risk in the entire county, the study intervention was implemented in 39% (n = 36), indicating 56 census tracts as potential areas for future HFS interventions. The Geographic information system based fire risk model is an underutilized but important tool for practice that allows community agencies to develop, plan, and evaluate their outreach efforts and ensure the most effective use of scarce resources. PMID- 26284632 TI - Does Payer Type Influence Pediatric Burn Outcomes? A National Study Using the Healthcare Cost and Utilization Project Kids' Inpatient Database. AB - Pediatric burns are a considerable source of injury in the United States. Socioeconomic status has been demonstrated to influence other disease outcomes. The goal of this study was to analyze national pediatric burn outcomes based on payer type. A retrospective study was designed using the Kids' Inpatient Database (KID), years 2000 to 2009. Patients 18 years of age and under with Major Diagnostic code number 22 for burn were included. A total of 22,965 patients were identified, estimating 37,856 discharges. Descriptive and bivariate statistics were performed. Multiple regression analysis was used to assess correlation of payer type with complications and length of stay (LOS). The majority of patients were Medicaid (52.3%). Medicaid patients were younger (4.25, P < .05), had a higher rate of being in the first quartile of their zipcode's income (46.26%, P < .05), and contained a higher proportion of African-Americans (30.01%, P < .05). Overall complication rate was higher among Medicaid patients than private insurance and self-pay patients (6.64 vs 5.51 and 4.35%, respectively, P = .11). Logistic regression analysis of complications showed that Medicaid coverage (P < .001) was associated with complications. The geometric mean LOS among Medicaid patients was 3.7 days compared with private insurance (3.5 days) and self-pay patients (3.1 days). Medicaid patients had longer LOS and more complications. Regression analysis revealed that payer type was a factor in LOS and overall complication rate. Identifying dissimilar outcomes based on patient and injury characteristics is critical in providing information on how to improve those outcomes. PMID- 26284633 TI - Active Dynamic Thermography is a Sensitive Method for Distinguishing Burn Wound Conversion. AB - Burn conversion is a contributor to morbidity that currently has no quantitative measurement system. Active dynamic thermography (ADT) has recently been characterized for the early assessment of burn wounds and resolves the three dimensional structure of materials by heat transfer analysis. As conversion is a product of physiological changes in three-dimensional structure, with subsequent modification of heat transfer properties, the authors hypothesize that ADT can specifically identify the process of burn conversion and serve as an important tool for burn care. A heated comb was used to create four contact burns separated by three interspaces on bilateral flanks of 18 rats, resulting in 144 burns and 108 interspaces. Wounds were imaged by ADT and laser Doppler imaging (LDI) pre- and post-injury through hour 36, with a subset undergoing biopsy collection. Direct analysis of thermographic and perfusion data revealed an increasing difference between burns and interspaces by ADT with increasing injury severity (P < .05), while LDI characterized the opposite. Comparison of stasis zones to burns reveals the ability of ADT to distinguish these two regions in both intermediate and deep burns at every assessment (P < .05). In addition, when wounds are grouped as converting or not converting, ADT identifies by hour 12, wounds that will convert (P < .05). LDI identifies by hour 4 wounds that will not (P < .05). This study has demonstrated that ADT can directly identify burn wound conversion, while LDI can identify nonconverting wounds. Further advancement of ADT technology has the potential to guide real-time interventional techniques. PMID- 26284634 TI - Predictors of Mortality Among Pediatric Burn Patients in East Africa. AB - Little is known about the outcomes of pediatric burn patients in resource-limited and rural locations of the developing world. In March 2013, our pediatric burn unit existing in this setting established an electronic registry of all patients. The authors analyzed the registry to determine overall mortality rates and predictors of mortality, including that of underweight status and body part burned. The secure electronic database of all admissions was reviewed for age, gender, weight, burn percentage (TBSA%), body part burned, cause/place of injury, length of stay, underweight status, surgery performed, reason for discharge, and mortality. Univariable and multivariable logistic regression was used to determine the variables associated with mortality. Kaplan-Meier curves were also analyzed. A total of 211 cases (59.7% male) admitted from March 2013 to June 2014 were reviewed. The median age, %TBSA, and length of stay were 2.0 years (1.3 3.3), 8.0% (5.0-13.4), and 8.5 days (4-14). The overall mortality rate was 15/211 (7.1%). Most injuries were unintentional (93.8%) scalds (85.3%) occurring in the home (98.1%). Two factors were significantly associated with mortality in the final multivariable model: %TBSA (odds ratio = 1.31 for 1% increase in %TBSA; 95% confidence interval = 1.17-1.46) and younger age (odds ratio = 0.20; 0.07-0.63). This study characterizes mortality among patients at a pediatric burn unit serving a rural population in the developing world. The majority of pediatric burns were unintentional scalds occurring in the home. %TBSA and lower age were the strongest predictors of mortality. Burn location and underweight status were not independent predictors of mortality. Overall mortality was 7.1%. These data are applicable to improving outcomes for patients in this burn unit and similar settings of its kind. PMID- 26284635 TI - Burn Ear Reconstruction Using Porous Polyethylene Implants and Tissue Expansion. AB - Reconstruction of the external ear after a burn is particularly challenging. The nature of the injury poses many problems including excessive scar tissue, poor blood supply, and the lack of adequate and appropriate materials for a framework. The use of costochondral grafts often leads to marginal outcomes which do not justify the morbidity. Children under the age of 10 years commonly have insufficient cartilage for a graft. Medpor (Stryker, Kalamazoo, MI) offers minimal morbidity and a very effective result. In this series, the authors describe the experience using Medpor and scalp tissue expansion to reconstruct severely burned ears. A total of 16 pediatric patients underwent 18 reconstructions, with two patients receiving bilateral procedures. All patients received Medpor implants. Thirteen patients were tissue expanded under the subgaleal plane before reconstruction, for concomitant scalp alopecia reconstruction. Eleven temporoparietal fascial flaps were performed. In the remaining patients, coverage of the implant was achieved by local advancement flaps. Only two patients had complications, with exposure of the construct after several years. In these two cases, the implants were removed. The experience has shown porous polyethylene reconstruction to be very efficient, with low morbidity and good cosmetic outcomes. Medpor is an excellent option for the reconstruction of both fully and partially burned ears as you may implant only the helical rim, base, or both pieces. The best results were achieved after tissue expansion and the use of the alopecic skin overlying a temporoparietal fascial flap. This has become the preferred method. PMID- 26284631 TI - Alcohol Modulation of the Postburn Hepatic Response. AB - The widespread and rapidly increasing trend of binge drinking is accompanied by a concomitant rise in the prevalence of trauma patients under the influence of alcohol at the time of their injury. Epidemiological evidence suggests up to half of all adult burn patients are intoxicated at the time of admission, and the presence of alcohol is an independent risk factor for death in the early stages post burn. As the major site of alcohol metabolism and toxicity, the liver is a critical determinant of postburn outcome, and experimental evidence implies an injury threshold exists beyond which burn-induced hepatic derangement is observed. Alcohol may lower this threshold for postburn hepatic damage through a variety of mechanisms including modulation of extrahepatic events, alteration of the gut-liver axis, and changes in signaling pathways. The direct and indirect effects of alcohol may prime the liver for the second-hit of many overlapping physiologic responses to burn injury. In an effort to gain a deeper understanding of how alcohol potentiates postburn hepatic damage, the authors summarize possible mechanisms by which alcohol modulates the postburn hepatic response. PMID- 26284637 TI - Need for Mechanical Ventilation in Pediatric Scald Burns: Why it Happens and Why it Matters. AB - Scald burns are the most common thermal injury among children. A small subset of pediatric scald burns are complicated by the need for mechanical ventilation (MV). Studies suggest that 4 to 5% of pediatric scald burns will require MV, and these patients tend to be younger with larger burns. Identifying why pediatric patients with scald burns require MV has remained unclear, and few studies have sought to elucidate possible mechanisms. After institutional review board approval, a retrospective review of all pediatric patients with scald burns admitted to the Burn Center between 2010 and 2013 was conducted. Variables collected included age, sex, weight, height, race, ethnicity, socioeconomic status or type of insurance, hospital length of stay, burn size and location, Department of Child and Family Services (DCFS) involvement, time to intubation from admission, reason for intubation, need for MV, duration of MV, need for operative intervention, 24-hour and 48-hour total fluid intake and urine output, glucose levels, infectious complications, comorbidities, and mortality. Patients who required MV were then compared with those who did not require MV to identify statistically significant differences between groups. The MV patients (n = 6) and nonventilated patients (n = 339) did not show significant differences in regards to gender, body mass index, ethnicity, and type of insurance; however, MV patients were younger and had larger burns. The mean age of MV patients was 8.2 + 5.0 months compared with 40.7 + 45.2 months for non-MV (P = .002). The mean percentage of TBSA burn in MV patients was 17.3 + 9.0% compared with 4.5 + 3.9% for non-MV (P < .001). Burn location was significant, and 66.6% of MV patients had burns on the face or neck compared with 23.6% of non-MV (P = .015). MV patients were more likely to have been victims of child abuse, as DCFS was involved in 67% of MV patients vs. 28% of non-MV patients (P = .036). Fifty percent of patients requiring MV had either a preceding upper respiratory infection, diagnosis of asthma, or congenital defects, compared with 6% of non-MV patients (P = .004). MV patients received more fluids for 48 hours compared with non-MV patients (2275.7 vs. 1332.3 ml, P = .013) and had a higher 48-hour urine output (2.34 vs. 1.34 ml/kg/hr, P = .013). Pediatric scald burns that require MV have an increased mortality risk and length of stay. MV patients were younger with larger burns. They received more fluids than non-MV patients, and child abuse, asthma, and stress hyperglycemia within the first 72 hours of injury were common among MV patients. Importantly, burn size and previous history of asthma were found to be independent predictors of the need for MV. PMID- 26284636 TI - Practice Guidelines for Cardiovascular Fitness and Strengthening Exercise Prescription After Burn Injury. AB - The objective of this review was to systematically evaluate the available clinical evidence for the prescription of strength training and cardiovascular endurance exercise programs for pediatric and adult burn survivors so that practice guidelines could be proposed. This review provides evidence-based recommendations specifically for rehabilitation professionals who are responsible for burn survivor rehabilitation. Summary recommendations were made after the literature was retrieved by systematic review, was critically appraised by multiple authors and the level of evidence determined in accordance with the Oxford Centre for Evidence-based Medicine criteria. Although gaps in the literature persist and should be addressed in future research projects, currently, strong research evidence supports the prescription of strength training and aerobic conditioning exercise programs for both adult and pediatric burn survivors when in the presence of strength limitations and/or decreased cardiovascular endurance after evaluation. PMID- 26284638 TI - Is Real-Time Feedback of Burn-Specific Patient-Reported Outcome Measures in Clinical Settings Practical and Useful? A Pilot Study Implementing the Young Adult Burn Outcome Questionnaire. AB - Long-term follow-up care of survivors after burn injuries can potentially be improved by the application of patient-reported outcome measures (PROMs). PROMs can inform clinical decision-making and foster communication between the patient and provider. There are no previous reports using real-time, burn-specific PROMs in clinical practice to track and benchmark burn recovery over time. This study examines the feasibility of a computerized, burn-specific PROM, the Young Adult Burn Outcome Questionnaire (YABOQ), with real-time benchmarking feedback in a burn outpatient practice. The YABOQ was redesigned for formatting and presentation purposes using images and transcribed to a computerized format. The redesigned questionnaire was administered to young adult burn survivors (ages 19 30 years, 1-24 months from injury) via an ipad platform in the office before outpatient visits. A report including recovery curves benchmarked to a nonburned relatively healthy age-matched population and to patients with similar injuries was produced for the domains of physical function and social function limited by appearance. A copy of the domain reports as well as a complete copy of the patient's responses to all domain questions was provided for use during the clinical visit. Patients and clinicians completed satisfaction surveys at the conclusion of the visit. Free-text responses, included in the satisfaction surveys, were treated as qualitative data adding contextual information about the assessment of feasibility. Eleven patients and their providers completed the study for 12 clinical visits. All patients found the ipad survey and report "easy" or "very easy" to use. In nine instances, patients "agreed" or "strongly agreed" that it helped them communicate their situation to their doctor/nurse practitioner. Patients "agreed" or "strongly agreed" that the report helped them understand their course of recovery in 10 visits. In 11 visits, the patients "agreed" or "strongly agreed" that they would recommend this feedback to others. Qualitative comments included: "it helped organize my thoughts of recovery," "it opened lines of communication with the doctor," "it showed me how far I have come, and how far I need to go," and "it raised questions I would not have thought of." Only four of 12 provider surveys agreed that it helped them understand a patient's condition; however, in two visits, the providers stated that it helped identify a pertinent clinical issue. During two visits, providers stated that a treatment plan was discussed or recommended based on the survey results. Separately, qualitative comments from the providers included "survey was not sensitive enough to identify that this patient needed surgery for their scars." This is the first report describing clinical use of a burn-specific patient reported outcome measure. Real-time feedback using the ipad YABOQ was well received for the most part by the clinicians and burn survivors in the outpatient clinic setting. The information provided by the reports can be tested in a future randomized controlled clinical study evaluating impacts on physician decisions. PMID- 26284639 TI - A Novel Biodegradable Polyurethane Matrix for Auricular Cartilage Repair: An In Vitro and In Vivo Study. AB - Auricular reconstruction poses a challenge for reconstructive and burns surgeons. Techniques involving cartilage tissue engineering have shown potential in recent years. A biodegradable polyurethane matrix developed for dermal reconstruction offers an alternative to autologous, allogeneic, or xenogeneic biologicals for cartilage reconstruction. This study assesses such a polyurethane matrix for this indication in vivo and in vitro. To evaluate intrinsic cartilage repair, three pigs underwent auricular surgery to create excisional cartilage +/- perichondrial defects, measuring 2 * 3 cm in each ear, into which acellular polyurethane matrices were implanted. Biopsies were taken at day 28 for histological assessment. Porcine chondrocytes +/- perichondrocytes were cultured and seeded in vitro onto 1 * 1 cm polyurethane scaffolds. The total culture period was 42 days; confocal, histological, and immunohistochemical analyses of scaffold cultures were performed on days 14, 28, and 42. In vivo, the polyurethane matrices integrated with granulation tissue filling all biopsy samples. Minimal neocartilage invasion was observed marginally on some samples. Tissue composition was identical between ears whether perichondrium was left intact, or not. In vitro, the polyurethane matrix was biocompatible with chondrocytes +/- perichondrocytes and supported production of extracellular matrix and Type II collagen. No difference was observed between chondrocyte culture alone and chondrocyte/perichondrocyte scaffold coculture. The polyurethane matrix successfully integrated into the auricular defect and was a suitable scaffold in vitro for cartilage tissue engineering, demonstrating its potential application in auricular reconstruction. PMID- 26284640 TI - More Than One Third of Intubations in Patients Transferred to Burn Centers are Unnecessary: Proposed Guidelines for Appropriate Intubation of the Burn Patient. AB - Advanced Burn Life Support emphasizes endotracheal intubation for patients with facial burns before transfer to a burn center to prevent airway obstruction. Many patients are intubated before transport and are often extubated shortly after burn center arrival. We hypothesize that many intubations performed before burn center transport are unnecessary. We conducted a retrospective review of all adults who were intubated before burn transfer and survived to discharge from August 2003 to June 2013. Intubations that had 2 or fewer ventilator days (i.e., potentially unnecessary intubations) were compared with those lasting longer than 2 days. Data collected included age, ventilator days, length of stay, % TBSA burn, % second degree, % third degree, % second degree face burn, % third degree face burn, and origin of burns. A total of 416 patient met inclusion criteria. Of these, 129 patients (31.0%) were intubated less than or equal to 1 day, and a total of 171 (40.1%) patients remained intubated for less than or equal to 2 days. Patients who were intubated less than or equal to 2 days differed from those intubated more than 2 days with respect to % TBSA burn (10.2 +/- 8.1 vs 30.8 +/- 19.7, P < .001), % third degree burn (2.84 +/- 5.6 vs 22.5 +/- 19.6, P < .001), % third degree face burn (0.14 +/- 0.7 vs 0.94 +/- 1.9, P < .001), and hospital days (11.7 +/- 10.6 vs 50.7 +/- 43.7, P < .001). Additionally, patients who were intubated less than or equal to 2 days were more likely to have been intubated in the pre-burn center setting (74.9% vs 51.8%, P < .001) and to have been burned outdoors (42.1% vs 24.9%; P < .001) than those who were intubated more than 2 days. Multivariate analysis revealed that intubation longer than 2 days was independently associated with older age and larger % TBSA burn. There were no reintubations in patients who were intubated 2 days or less. As a burn community, we have emphasized early intubation before transfer for those who have sustained significant burns, inhalational injury, or facial burns. Unfortunately, this has led to many potentially unnecessary intubations that expose patients to unnecessary complications. Although early intubation is a lifesaving intervention for many burn patients, criteria should be developed to determine when intubation is not needed. PMID- 26284641 TI - Morphological Changes in Subcutaneous White Adipose Tissue After Severe Burn Injury. AB - Severe burn injury produces a plethora of metabolic abnormalities which contribute to the prolonged morbidity of burn survivors. The authors have recently demonstrated trans-differentiation of white adipose tissue (WAT) after burn trauma, toward a more thermogenic phenotype. However, the impact of burn injury on subcutaneous WAT (sWAT) morphology in humans is unknown. Here, the authors studied the effect of severe burn injury on the architecture of sWAT. sWAT was collected from 11 severely burned children (11 +/- 3 years; 55 +/- 16% total BSA burned) and 12 nonburned healthy children (9 +/- 3 years). Histology, electron microscopy, immunohistochemistry, and immunofluorescence were performed on fixed adipose tissue sections. sWAT cytokine and collagen concentrations were measured by multiplex assay and sirius/fast green staining method, respectively. sWAT histology demonstrated multiple fat droplets, significantly (P < .05) reduced mean cell size (104 +/- 6 vs 68 +/- 3 MUm) and higher collagen content (7 +/- 0.8 vs 4 +/- 0.4) in burn patients. sWAT from burn victims stained positive for CD68 suggesting infiltration of macrophages. Furthermore, electron microscopic analysis showed multiple fat droplets and greater mitochondrial abundance in sWAT of burn survivors. In agreement with this, mitochondrial respiratory capacity in the leak and coupled state increased by 100% in sWAT of burned children from 1 to 3 weeks postinjury. The cytokines IL-6, IL-8, IL-13, IL 1a, IL-1b, MCP-1, and TNF-alpha were all significantly greater in the sWAT of burned children versus healthy children (P < .05). Furthermore, IL-6, IL-8, IL1 a, IL-1b, and TNF-alpha significantly increased after injury in sWAT of burned children (P < .05). This study provides detailed evidence of morphological and functional changes in sWAT of burn survivors which was associated with tissue inflammation. A better understanding of morphological and functional changes in sWAT will help discern the mechanisms underlying hypermetabolism in burned patients. PMID- 26284642 TI - The National Incidence and Resource Utilization of Burn Injuries Sustained While Smoking on Home Oxygen Therapy. AB - Considerable risk of burn injury exists for those patients on home oxygen therapy (HOT) who continue to smoke. In this study, the authors sought to establish the national incidence of burns incurred while smoking on HOT and to determine the resource utilization and sequelae of these injuries. A retrospective review of the American Burn Association's National Burn Repository was conducted to identify patients burned while on HOT during the years 2002 to 2011. Duplicate entries, as well as records of follow-up visits and readmissions, were removed. Univariate analysis was used to compare the differences between patients sustaining burn injuries related to HOT and patients with other mechanisms of injury. Multivariate analysis provided odds ratios for mortality controlling for all significant variables. The frequency of burns sustained on HOT significantly increased during the 10-year period reviewed and were associated with increased comorbidities and certain complications. Compared with non-HOT injuries, HOT injuries had higher incidence of inhalation injury and mortality. Inhalation injury was the strongest predictor of mortality in HOT burn injuries. The likelihood of poor prognosis was even more pronounced in patients who required intubation. Smoking was responsible for 83% of the HOT burn injuries described here. Therefore, smoking cessation counseling and treatment should be mandatory in all patients prescribed HOT. PMID- 26284643 TI - Development of a Fire Risk Model to Identify Areas of Increased Potential for Fire Occurrences. AB - The purposes of this study were to use geographic information systems to create a cartographic risk model predicting areas of increased potential for fire occurrences and to validate the model. Seven literature-identified risk factors associated with burn injury were older than 65 years, non-white race, below high school education, low socioeconomic status, rented housing, year home built, and home value. Geographic information system methods were used in risk factor model development. Model validation occurred using residential county fire dispatch data and statistical analysis. Areas of high and severe risk were primarily located in the northwestern and central county regions. A strong correlation (r = .66) was found between risk model scores and fire incidence rates. Significant differences in mean fire rates by risk category (F (187,3) = 87.58, P < .0001) were found, with the exception of the low and medium risk categories. Fire incidence rates among census tracts showed positive spatial autocorrelation (Moran's I = 0.542, P < .0001) producing a map showing a significant cluster of high fire incidence in the northwestern region. The risk model has potential to lead to more targeted and effective fire prevention education programs. Such models would allow fire departments to focus limited resources in areas of highest fire risk. PMID- 26284645 TI - Coronary Flow Velocity Reserve in Burn Injury: A Prospective Clinical Cohort Study. AB - The authors sought to evaluate coronary microvascular function and left ventricular diastolic dysfunction using transthoracic Doppler echocardiography in burn patients. In this study, 32 adult burn patients with partial or full thickness scald burns that were hospitalized and treated were included. The control group was matched for age and sex and was composed of otherwise healthy volunteers. Transthoracic Doppler echocardiography examinations and simultaneous laboratory tests for cardiac evaluation were performed on the sixth month after burn injury as well as with the control group. High-sensitivity C-reactive protein levels were significantly higher in the burn patients than in controls (5.17 +/- 3.86 vs 2.42 +/- 1.78; P = .001). Lateral isovolumic relaxation time was significantly higher in the burn injury group than in the control group (92.7 +/- 15.7 vs 85.5 +/- 8.3; P = .03). Baseline coronary diastolic peak flow velocity of the left anterior descending artery was similar in both groups. However, hyperemic diastolic peak flow velocity and coronary flow velocity reserve (2.26 +/- 0.48 vs 2.94 +/- 0.47; P < .001) were significantly lower in the burn injury group than in the control group. Coronary flow velocity reserve was significantly and inversely correlated with high-sensitivity C-reactive protein, burn ratio, creatinine, and mitral A-wave max velocity. At the sixth month of treatment, burn patients had high-sensitivity C-reactive protein levels during this period, suggesting that inflammation still exists. In addition, subclinical coronary microvascular and left ventricular diastolic dysfunction can occur in burn patients without traditional cardiovascular risk factors. However, these results must be supported by additional studies. PMID- 26284646 TI - Development and Implementation of an Innovative Burn Nursing Handbook for Quality Improvement. AB - Evidence-based burn nursing literature is extremely limited and often nonexistent. As a result, there is a lack of standardization in burn nursing care. Our objective was to evaluate burn nursing knowledge at an academic medical center and to implement innovative educational tools to enhance staff competency and improve the quality of care. A collaboration of practicing clinical nurses developed a 24-question knowledge assessment survey (presurvey) to evaluate fundamental burn nursing knowledge (fluid management, burn pathophysiology, burn related procedures, wound care, and infection control). Pre-education knowledge surveys were administered to 59 burn nurses electronically. A writing team of new and experienced nurses was established and a 51-page handbook focusing on areas of need identified in the survey developed. This book was disseminated to staff as required for reading. Post-educational surveys were sent to the same nurses who completed the initial survey. Forty-six nurses (46/59, 78.0%) completed the survey, with a mean (SD) of 55.9 (11.0)% of questions being answered correctly. Postsurveys sent to the same 46 nurses who completed the presurvey had a response rate of 78.3% (36/46). We observed a significant increase in correctly answered questions (mean [SD]: 69.6 [8.7]%, P < .001) in the postsurvey intervention. The handbook improved education and significantly improved overall fundamental burn knowledge of practicing nursing staff. The use of electronic surveys to drive development of targeted educational interventions provides evidence-based tools for establishing burn nursing standards and developing quality improvement metrics. PMID- 26284647 TI - Simultaneous Extended ALT Flaps for Foot Salvage After Severe Frostbite. AB - Plantar area reconstruction represents the most challenging part of the lower limb. The anterolateral thigh (ALT) flap proved to be a versatile flap for this special area. Herein, we present the application of bilateral ALT free flaps for foot salvage after frostbite injury and long-term follow-up. Single perforator bilateral ALT flaps (304 and 320 cm(2)) were harvested and anastomosed to posterior tibial vessels. The lateral femoral cutaneous nerve was anastomosed to the calcaneal branches of the posterior tibial nerve. The two-point discrimination test showed values from 16 to 28 mm in different flap areas 5 years later. The patient is able to walk with crutches. This is the first case report of bilateral ALT for foot salvage. PMID- 26284648 TI - "It Happened in Seconds" Firefighter Burn Prevention Program: Evaluation of a "Train the Trainer" Course. AB - Each year, there are approximately 100 firefighter fatalities and tens of thousands of injuries in the United States. 'It Happened in Seconds' is a firefighter burn injury awareness program offered to firefighters nationwide. The course focuses on situational awareness, personal protective equipment, and burn injury prevention. In order to create more instructors, a 'Train the Trainer' instructor course was developed to prepare experienced firefighters and healthcare providers from around the United States to teach firefighters in their respective communities. This study evaluates trainees' perception of the instructor course. Three instructor courses were held in a period between November 2013 and January 2015. Trainees were asked to complete both precourse/postcourse assessments and provide demographics. In both surveys, trainees rated their confidence to instruct firefighters about burn prevention and their awareness about firefighter-specific burn issues using a 5-point Likert Scale (1 = none and 5 = high). The postassessment asked if trainees thought the course should be mandatory for all firefighters. Pretest and post-test scores were compared using a Wilcoxon's signed-rank test. A total of 140 experienced firefighters and healthcare professionals completed the Train the Trainer course. The average age was 40 +/- 9 years, and 41 were women and 99 men. The average trainee had 13.6 +/- 9 years experience in his or her respective job and 11 +/- 9 years experience in burn care. Trainees reported a significant increase in their confidence to instruct firefighters about burn prevention (2.9/5 precourse vs. 4.5/5 postcourse, P < .0001) and in their current awareness of firefighter specific burn issues (3.2 precourse vs. 4.4 postcourse, P < .0001). In the postcourse assessment, 139 of 140 respondents agreed that the 'It Happened in Seconds' course should be mandatory for all firefighters. This study showed that experienced firefighters and healthcare professionals thought that the course significantly improved their awareness level of issues specific to firefighter burn injury as well as their confidence in teaching these concepts to firefighters. Based on this positive evaluation, additional instructors will be trained to provide the course to all firefighters nationwide. Additional research must be conducted to evaluate whether the 'It Happened in Seconds' course results in a decreased rate of firefighter burn injuries. PMID- 26284649 TI - Diversified Control Paths: A Significant Way Disease Genes Perturb the Human Regulatory Network. AB - BACKGROUND: The complexity of biological systems motivates us to use the underlying networks to provide deep understanding of disease etiology and the human diseases are viewed as perturbations of dynamic properties of networks. Control theory that deals with dynamic systems has been successfully used to capture systems-level knowledge in large amount of quantitative biological interactions. But from the perspective of system control, the ways by which multiple genetic factors jointly perturb a disease phenotype still remain. RESULTS: In this work, we combine tools from control theory and network science to address the diversified control paths in complex networks. Then the ways by which the disease genes perturb biological systems are identified and quantified by the control paths in a human regulatory network. Furthermore, as an application, prioritization of candidate genes is presented by use of control path analysis and gene ontology annotation for definition of similarities. We use leave-one-out cross-validation to evaluate the ability of finding the gene disease relationship. Results have shown compatible performance with previous sophisticated works, especially in directed systems. CONCLUSIONS: Our results inspire a deeper understanding of molecular mechanisms that drive pathological processes. Diversified control paths offer a basis for integrated intervention techniques which will ultimately lead to the development of novel therapeutic strategies. PMID- 26284650 TI - Sympathetic Activation Does Not Affect the Cardiac and Respiratory Contribution to the Relationship between Blood Pressure and Pial Artery Pulsation Oscillations in Healthy Subjects. AB - INTRODUCTION: Using a novel method called near-infrared transillumination backscattering sounding (NIR-T/BSS) that allows for the non-invasive measurement of pial artery pulsation (cc-TQ) and subarachnoid width (sas-TQ) in humans, we assessed the influence of sympathetic activation on the cardiac and respiratory contribution to blood pressure (BP) cc-TQ oscillations in healthy subjects. METHODS: The pial artery and subarachnoid width response to handgrip (HGT) and cold test (CT) were studied in 20 healthy subjects. The cc-TQ and sas-TQ were measured using NIR-T/BSS; cerebral blood flow velocity (CBFV) was measured using Doppler ultrasound of the left internal carotid artery; heart rate (HR) and beat to-beat mean BP were recorded using a continuous finger-pulse photoplethysmography; respiratory rate (RR), minute ventilation (MV), end-tidal CO2 (EtCO2) and end-tidal O2 (EtO2) were measured using a metabolic and spirometry module of the medical monitoring system. Wavelet transform analysis was used to assess the relationship between BP and cc-TQ oscillations. RESULTS: HGT evoked an increase in BP (+15.9%; P<0.001), HR (14.7; P<0.001), SaO2 (+0.5; P<0.001) EtO2 (+2.1; P<0.05) RR (+9.2%; P = 0.05) and MV (+15.5%; P<0.001), while sas-TQ was diminished (-8.12%; P<0.001), and a clear trend toward cc-TQ decline was observed (-11.0%; NS). CBFV (+2.9%; NS) and EtCO2 (-0.7; NS) did not change during HGT. CT evoked an increase in BP (+7.4%; P<0.001), sas-TQ (+3.5%; P<0.05) and SaO2(+0.3%; P<0.05). HR (+2.3%; NS), CBFV (+2.0%; NS), EtO2 (-0.7%; NS) and EtCO2 (+0.9%; NS) remained unchanged. A trend toward decreased cc-TQ was observed (-5.1%; NS). The sas-TQ response was biphasic with elevation during the first 40 seconds (+8.8% vs. baseline; P<0.001) and subsequent decline (+4.1% vs. baseline; P<0.05). No change with respect to wavelet coherence and wavelet phase coherence was found between the BP and cc-TQ oscillations. CONCLUSIONS: Short sympathetic activation does not affect the cardiac and respiratory contribution to the relationship between BP-cc-TQ oscillations. HGT and CT display divergent effects on the width of the subarachnoid space, an indirect marker of changes in intracranial pressure. PMID- 26284651 TI - Photochromism and Photomagnetism of a 3d-4f Hexacyanoferrate at Room Temperature. AB - Polycyanometallate compounds with both photochromism and photomagnetism have appealing applications in optical switches and memories, but such optical behaviors were essentially restricted to the cryogenic temperature. We realized, for the first time, the photochromism and photomagnetism of 3d-4f hexacyanoferrates at room temperature (RT) in [Eu(III)(18C6)(H2O)3]Fe(III)(CN)6.2H2O (18C6 = 18-crown-6). Photoinduced electron transfer (PET) from crown to Fe(III) yields long-lived charge-separated species at RT in air in the solid state and also weakens the magnetic susceptibility significantly. The PET mechanism and changing trend of photomagnetism differ significantly from those reported for known 3d-4f hexacyanoferrates. This work not only develops a new type of inorganic-organic hybrid photochromic material but opens a new avenue for RT photomagnetic polycyanometallate compounds. PMID- 26284653 TI - Do Childhood Infections Contribute to Adult Cardiometabolic Diseases? PMID- 26284652 TI - Effectiveness of the Ten-valent Pneumococcal Conjugate Vaccine Against Tympanostomy Tube Placements in a Cluster-randomized Trial. AB - BACKGROUND: We evaluated the impact of the new pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10, GSK Vaccines) on tympanostomy tube placements (TTPs). METHODS: Finnish Invasive Pneumococcal disease vaccine trial was a nationwide phase III/IV cluster-randomized, double-blind trial. Children younger than 19 months received PHiD-CV10 in two thirds of clusters (N = 52) or hepatitis B or A vaccine as control in 26 clusters according to 3 + 1 or 2 + 1 schedules (infants younger than 7 months) or catch-up schedules. A secondary objective of the trial was to assess vaccine effectiveness (VE) against TTPs in children who received at least one vaccine dose before or after 7 months of age. Blinded follow-up lasted from the date of first vaccination (from February 2009 through October 2010) to December 31, 2011. Outcome data were collected through the National Care register and Social Insurance Institution reimbursement register. RESULTS: More than 47,000 children were enrolled. In 30,527 infants younger than 7 months of age at enrolment, 4369 TTPs were reported in 3594 subjects. The incidence was 7.9 per 100 person-years in the infant control cohort. The VE estimate was 13% [95% confidence interval (CI): -2% to 26%] for combined PHiD-CV10 3 + 1 and 2 + 1 infant schedules. The VE estimates for the 3 + 1 and 2 + 1 infant schedules when estimated separately were similar. For the catch-up schedules, the VE was 11% (95% CI: -7% to 26%) for children enrolled at 7-11 months of age and -1% (95% CI: -21% to 16%) for children enrolled at 12-18 months of age. CONCLUSIONS: Our study results suggest that PHiD-CV10 immunization according to a 3 + 1 or 2 + 1 schedule initiated before 12 months of age may reduce the frequency of TTPs, although the primary analysis did not reach statistical significance. PMID- 26284654 TI - Extended-Spectrum beta-Lactamases and/or Carbapenemases-Producing Enterobacteriaceae Isolated from Retail Chicken Meat in Zagazig, Egypt. AB - OBJECTIVES: The aim of the present study was to determine the prevalence and to characterize extended-spectrum beta-lactamases- and/or carbapenemases-producing Enterobacteriaceae among Enterobacteriaceae isolated from retail chicken meat in Zagazig, Egypt. METHODS: One hundred and six Enterobacteriaceae isolates were collected from retail chicken meat samples purchased in Zagazig, Egypt in 2013. Species identification was done by MALDI-TOF MS. Screening for ESBL-E was performed by inoculation of isolates recovered from meat samples onto the EbSA (Cepheid Benelux, Apeldoorn, the Netherlands) selective screening agar. ESBL production was confirmed by combination disc diffusion test with clavulanic acid (Rosco, Taastrup, Denmark). Carbapenemases production was confirmed with double disk synergy tests. Resistance genes were characterized by PCR with specific primers for TEM, SHV, and CTX-M and carbapenemases (KPC, NDM, OXA-48, IMP and VIM). PCR products of CTX-M genes were purified and sequenced. Phylogenetic grouping of E. coli was performed by a PCR-based method. RESULTS: Of these 106 isolates 69 (65.09%) were ESBL producers. Twelve (11.32%) of these isolates were also phenotypically class B carbapenemases producer. TEM genes were detected in 61 (57.55%) isolates. 49 (46.23%) isolates harbored CTX-M genes, and 25 (23.58%) carried genes of the SHV family. All CPE belonged to the NDM group. The predominant CTX-M sequence type was CTX-M-15 (89.80%). The majority (80%) of the ESBL-EC belonged to low virulence phylogroups A and B1. CONCLUSIONS: This is the first study from Egypt reporting high rates of ESBLs and carbapenemases (65.09% and 11.32%, respectively) in Enterobacteriaceae isolated from retail chicken meat. These results raise serious concerns about public health and food safety as retail meat could serve as a reservoir for these resistant bacteria which could be transferred to humans through the food chain. PMID- 26284656 TI - Changes in Remotely Sensed Vegetation Growth Trend in the Heihe Basin of Arid Northwestern China. AB - The Heihe River Basin (HRB) is the second largest inland river basin in China, characterized by high diversity in geomorphology and irrigated agriculture in middle reaches. To improve the knowledge about the relationship between biotic and hydrological processes, this study used Global Inventory Modeling and Mapping Studies Normalized Difference Vegetation Index (NDVI) data (1982-2006) to analyze spatiotemporal variations in vegetation growth by using the Mann-Kendall test together with Sen's slope estimator. The results indicate that 10.1% and 1.6% of basin area exhibit statistically significant (p < 0.05) upward and downward trends, and maximum magnitude is 0.066/10a and 0.026/10a, respectively. More specifically, an increasing trend was observed in the Qilian Mountains and Hexi Corridor and a decreasing trend detected in the transitional region between them. Increases in precipitation and temperature may be one possible reason for the changes of vegetation growth in the Qilian Mountains. And decreasing trend in transitional region may be driven by the changes in precipitation. Increases of irrigation contribute to the upward trend of NDVI for cropland in the Hexi Corridor, reflecting that agricultural development becomes more intensive. Our study demonstrates the complexity of the response of vegetation growth in the HRB to climate change and anthropogenic activities and correspondingly adopting mechanistic ecological models capable of describing both factors is favorable for reasonable predictions of future vegetation growth. It is also indicated that improving irrigation water use efficiency is one practical strategy to balance water demand between human and natural ecosystems in the HRB. PMID- 26284655 TI - In Vivo Evidence for Lysosome Depletion and Impaired Autophagic Clearance in Hereditary Spastic Paraplegia Type SPG11. AB - Hereditary spastic paraplegia (HSP) is characterized by a dying back degeneration of corticospinal axons which leads to progressive weakness and spasticity of the legs. SPG11 is the most common autosomal-recessive form of HSPs and is caused by mutations in SPG11. A recent in vitro study suggested that Spatacsin, the respective gene product, is needed for the recycling of lysosomes from autolysosomes, a process known as autophagic lysosome reformation. The relevance of this observation for hereditary spastic paraplegia, however, has remained unclear. Here, we report that disruption of Spatacsin in mice indeed causes hereditary spastic paraplegia-like phenotypes with loss of cortical neurons and Purkinje cells. Degenerating neurons accumulate autofluorescent material, which stains for the lysosomal protein Lamp1 and for p62, a marker of substrate destined to be degraded by autophagy, and hence appears to be related to autolysosomes. Supporting a more generalized defect of autophagy, levels of lipidated LC3 are increased in Spatacsin knockout mouse embryonic fibrobasts (MEFs). Though distinct parameters of lysosomal function like processing of cathepsin D and lysosomal pH are preserved, lysosome numbers are reduced in knockout MEFs and the recovery of lysosomes during sustained starvation impaired consistent with a defect of autophagic lysosome reformation. Because lysosomes are reduced in cortical neurons and Purkinje cells in vivo, we propose that the decreased number of lysosomes available for fusion with autophagosomes impairs autolysosomal clearance, results in the accumulation of undegraded material and finally causes death of particularly sensitive neurons like cortical motoneurons and Purkinje cells in knockout mice. PMID- 26284657 TI - Cyclohexenylboration of Aldehydes and Ketones with the Borabicyclo[3.3.2]decanes (BBDs). AB - Asymmetric hydroboration of 1,3-cyclohexadiene with 4R produces the allylborane 5RR as essentially a single diastereomer (i.e., no observable 5RS), and its addition to representative aldehydes provides 9RS (52-75%) with excellent selectivity (94-99% ee). By contrast, a similar sequence with the 10-Ph-BBD reagent, 14R, results in a ca. 45:55 mixture of 15RR and 15RS. However, their addition to methyl ketones provides the corresponding 3 degrees -homoallylic alcohols (18RS) with excellent selectivity (80-99% ee) but in low yields (15-52%) because 15RS is unreactive toward either allylboration or isomerization to 15RR. Thus, with 2 equiv of 15, the yield of 18 (R = Ph) is increased from 52% to 85%. Boranes 5SS and 15SS provide enantiomeric alcohols. PMID- 26284658 TI - Impacts of Rotational Grazing on Soil Carbon in Native Grass-Based Pastures in Southern Australia. AB - Rotational grazing management strategies have been promoted as a way to improve the sustainability of native grass-based pasture systems. From disturbance ecology theory, rotational grazing relative to continuous grazing can increase pasture productivity by allowing vegetation to recover after short intense grazing periods. This project sought to assess whether soil organic carbon (SOC) stocks would also increase with adoption of rotational grazing management. Twelve pairs of rotationally and continuously grazed paddocks were sampled across a rainfall gradient in South Australia. Pasture productivity approximated as the normalized difference vegetation index (NDVI) was on average no different between management categories, but when the data from all sites were aggregated as log response ratios (rotational/continuous) a significant positive trend of increasing NDVI under rotational grazing relative to continuous grazing was found (R2 = 0.52). Mean SOC stocks (0-30 cm) were 48.3 Mg C ha-1 with a range of 20-80 Mg C ha-1 across the study area with no differences between grazing management categories. SOC stocks were well correlated with rainfall and temperature (multiple linear regression R2 = 0.61). After removing the influence of climate on SOC stocks, the management variables, rest periods, stocking rate and grazing days, were found to be significantly correlated with SOC, explaining 22% of the variance in SOC, but there were still no clear differences in SOC stocks at paired sites. We suggest three reasons for the lack of SOC response. First, changes in plant productivity and turnover in low-medium rainfall regions due to changes in grazing management are small and slow, so we would only expect at best small incremental changes in SOC stocks. This is compounded by the inherent variability within and between paddocks making detection of a small real change difficult on short timescales. Lastly, the management data suggests that there is a gradation in implementation of rotational grazing and the use of two fixed categories (i.e. rotational v. continuous) may not be the most appropriate method of comparing diverse management styles. PMID- 26284659 TI - Looking for logic. PMID- 26284660 TI - A chemocentric view of the natural product inventory. PMID- 26284668 TI - Protein degradation: Prime time for PROTACs. PMID- 26284669 TI - Carbohydrates: A phenol sandwich fights diabetes. PMID- 26284670 TI - Methods: A small-molecule SMASh hit. PMID- 26284661 TI - Minimum Information about a Biosynthetic Gene cluster. PMID- 26284671 TI - Computational approaches to natural product discovery. AB - Starting with the earliest Streptomyces genome sequences, the promise of natural product genome mining has been captivating: genomics and bioinformatics would transform compound discovery from an ad hoc pursuit to a high-throughput endeavor. Until recently, however, genome mining has advanced natural product discovery only modestly. Here, we argue that the development of algorithms to mine the continuously increasing amounts of (meta)genomic data will enable the promise of genome mining to be realized. We review computational strategies that have been developed to identify biosynthetic gene clusters in genome sequences and predict the chemical structures of their products. We then discuss networking strategies that can systematize large volumes of genetic and chemical data and connect genomic information to metabolomic and phenotypic data. Finally, we provide a vision of what natural product discovery might look like in the future, specifically considering longstanding questions in microbial ecology regarding the roles of metabolites in interspecies interactions. PMID- 26284672 TI - Reinvigorating natural product combinatorial biosynthesis with synthetic biology. AB - Natural products continue to play a pivotal role in drug-discovery efforts and in the understanding if human health. The ability to extend nature's chemistry through combinatorial biosynthesis--altering functional groups, regiochemistry and scaffold backbones through the manipulation of biosynthetic enzymes--offers unique opportunities to create natural product analogs. Incorporating emerging synthetic biology techniques has the potential to further accelerate the refinement of combinatorial biosynthesis as a robust platform for the diversification of natural chemical drug leads. Two decades after the field originated, we discuss the current limitations, the realities and the state of the art of combinatorial biosynthesis, including the engineering of substrate specificity of biosynthetic enzymes and the development of heterologous expression systems for biosynthetic pathways. We also propose a new perspective for the combinatorial biosynthesis of natural products that could reinvigorate drug discovery by using synthetic biology in combination with synthetic chemistry. PMID- 26284675 TI - Erratum: Hydrolysis of 2'3'-cGAMP by ENPP1 and design of nonhydrolyzable analogs. PMID- 26284673 TI - The structural biology of biosynthetic megaenzymes. AB - The modular polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs) are among the largest and most complicated enzymes in nature. In these biosynthetic systems, independently folding protein domains, which are organized into units called 'modules', operate in assembly-line fashion to construct polymeric chains and tailor their functionalities. Products of PKSs and NRPSs include a number of blockbuster medicines, and this has motivated researchers to understand how they operate so that they can be modified by genetic engineering. Beginning in the 1990s, structural biology has provided a number of key insights. The emerging picture is one of remarkable dynamics and conformational programming in which the chemical states of individual catalytic domains are communicated to the others, configuring the modules for the next stage in the biosynthesis. This unexpected level of complexity most likely accounts for the low success rate of empirical genetic engineering experiments and suggests ways forward for productive megaenzyme synthetic biology. PMID- 26284676 TI - Corrigendum: Local and macroscopic electrostatic interactions in single alpha helices. PMID- 26284674 TI - Translating biosynthetic gene clusters into fungal armor and weaponry. AB - Filamentous fungi are renowned for the production of a diverse array of secondary metabolites (SMs) where the genetic material required for synthesis of a SM is typically arrayed in a biosynthetic gene cluster (BGC). These natural products are valued for their bioactive properties stemming from their functions in fungal biology, key among those protection from abiotic and biotic stress and establishment of a secure niche. The producing fungus must not only avoid self harm from endogenous SMs but also deliver specific SMs at the right time to the right tissue requiring biochemical aid. This review highlights functions of BGCs beyond the enzymatic assembly of SMs, considering the timing and location of SM production and other proteins in the clusters that control SM activity. Specifically, self-protection is provided by both BGC-encoded mechanisms and non BGC subcellular containment of toxic SM precursors; delivery and timing is orchestrated through cellular trafficking patterns and stress- and developmental responsive transcriptional programs. PMID- 26284677 TI - Corrigendum: Sterol metabolism controls TH17 differentiation by generating endogenous RORgamma agonists. PMID- 26284678 TI - Corrigendum: SMN2 splice modulators enhance U1-pre-mRNA association and rescue SMA mice. PMID- 26284679 TI - Erratum: Structural basis of enzymatic benzene ring reduction. PMID- 26284680 TI - University Football Players, Postural Stability, and Concussions. AB - Concussion in football athletes is certainly more prevalent and has potentially serious outcomes. With current concerns and increasing return-to-play issues, additional assessment focus is needed. Division 1 college football athletes, from 18 to 20.9 years (n = 177; age, 19.7 +/- 1.2 years; height, 182.3 +/- 4.5 cm; weight, 97.3 +/- 10.6 kg), before fall practice, over a period of 3 years, underwent baseline postural stability testing (sensory organization test [SOT], NeuroCom). Individuals, who were diagnosed with a concussion (headache, dizziness, fatigue, confusion, or loss of consciousness) during practice or actual competition (n = 15; age, 18.9 +/- 0.9 years; height, 181.8 +/- 2.5 cm; weight, 86.6 +/- 3.6 kg), underwent serial evaluation after injury and 24 hours after concussion. As soon as the player was considered asymptomatic, the test was completed on the first and 14th day. A control group of noninjured male athletes (n = 15; age, 19.1 +/- 0.4 years; height, 178.2 +/- 3.2 cm; weight, 78.6 +/- 2.1 kg) were tested for the same time frame. This particular study was only one part of the total evaluation conducted for the concussed athlete's return to play. Results indicated that the concussion group had a statistically significant (p = 0.037) change from their baseline SOT score and the control group (p = 0.025). This change remained significant until day 14 of posttesting. These data indicate that the SOT, when available, may be a positive additional assessment of concussed college-aged football players. Professionals, when dealing with concussion in competitive sports, do need to continue to work together, but awareness of SOT assessments may also contribute to the return-to-play decisions. PMID- 26284681 TI - Altering Work to Rest Ratios Differentially Influences Fatigue Indices During Repeated Sprint Ability Testing. AB - This study examined the influence of recovery time on fatigue indices, performance (total work [TW], peak power [PP], and mean power [MP]), and oxygen consumption during repeated sprint ability (RSA) on a cycle ergometer. Eight recreationally-trained men performed 3 RSA protocols consisting of 10 * 6 s sprints with 12 s, 18 s, and 24 s rest intervals between each sprint. Fatigue indices were determined as percent decrement (%Dec) and rate of decline using either a log transform method or standard slope approach for TW, PP, and MP during respective RSA protocols. The maximal VO2 value in response to given sprint intervals and the minimal VO2 value in response to given rest periods (VO2 work and VO2 rest, respectively) were recorded. A repeated measures analysis of variance was used to analyze all variables. Average VO2 work was not different among rest interval trials. Average VO2 rest with 12 s rest was greater than 18 s and 24 s (2.16 +/- 0.17 L . min(-1), 1.91 +/- 0.18 L . min(-1), 1.72 +/- 0.15 L . min(-1), respectively), while 18 s was greater than 24 s. Average TW and MP were greater with 24 s rest than 12 s (4,604.44 +/- 915.98 J vs. 4,305.46 +/- 727.17 J, respectively), with no differences between RSA protocols for PP. No differences in %Dec were observed. Both methods of calculating rates of decline per sprint for PP and TW were greater during 12 s than 18 s or 24 s. Since changes were only noted between the 12 s and 24 s protocols, a 6 s differential in rest intervals may not be enough to elicit alterations in TW, PP, MP, or %Dec in RSA performance. Rate of decline may be a more sensitive measure of fatigue than %Dec. PMID- 26284684 TI - Design, Analysis, and Reporting of Crossover Trials for Inclusion in a Meta Analysis. AB - OBJECTIVE: To evaluate the characteristics of the design, analysis, and reporting of crossover trials for inclusion in a meta-analysis of treatment for primary open-angle glaucoma and to provide empirical evidence to inform the development of tools to assess the validity of the results from crossover trials and reporting guidelines. METHODS: We searched MEDLINE, EMBASE, and Cochrane's CENTRAL register for randomized crossover trials for a systematic review and network meta-analysis we are conducting. Two individuals independently screened the search results for eligibility and abstracted data from each included report. RESULTS: We identified 83 crossover trials eligible for inclusion. Issues affecting the risk of bias in crossover trials, such as carryover, period effects and missing data, were often ignored. Some trials failed to accommodate the within-individual differences in the analysis. For a large proportion of the trials, the authors tabulated the results as if they arose from a parallel design. Precision estimates properly accounting for the paired nature of the design were often unavailable from the study reports; consequently, to include trial findings in a meta-analysis would require further manipulation and assumptions. CONCLUSIONS: The high proportion of poorly reported analyses and results has the potential to affect whether crossover data should or can be included in a meta-analysis. There is pressing need for reporting guidelines for crossover trials. PMID- 26284683 TI - Rural-Urban Differences in Household Treatment-Seeking Behaviour for Suspected Malaria in Children at Bata District, Equatorial Guinea. AB - BACKGROUND: Malaria remains a major cause of morbidity and mortality among children under five years old in Equatorial Guinea. However, little is known about the community management of malaria and treatment-seeking patterns. We aimed to assess symptoms of children with reported malaria and treatment-seeking behaviour of their caretakers in rural and urban areas in the Bata District. METHODOLOGY: A cross-sectional study was conducted in the district of Bata and 440 houses were selected from 18 rural villages and 26 urban neighbourhoods. Differences between rural and urban caregivers and children with reported malaria were assessed through the chi-squared test for independence of categorical variables and the t-Student or the non-parametric Mann-Whitney test for normally or not-normally distributed continuous variables, respectively. RESULTS: Differences between rural and urban households were observed in caregiver treatment-seeking patterns. Fever was the main symptom associated with malaria in both areas. Malaria was treated first at home, particularly in rural areas. The second step was to seek treatment outside the home, mainly at hospital and Health Centre for rural households and at hospital and private clinic for urban ones. Artemether monotherapy was the antimalarial treatment prescribed most often. Households waited for more than 24 hours before seeking treatment outside and delays were longest in rural areas. The total cost of treatment was higher in urban than in rural areas in Bata. CONCLUSIONS: The delays in seeking treatment, the type of malaria therapy received and the cost of treatment are the principal problems found in Bata District. Important steps for reducing malaria morbidity and mortality in this area are to provide sufficient supplies of effective antimalarial drugs and to improve malaria treatment skills in households and in both public and private sectors. PMID- 26284685 TI - Increased Dietary Salt Intake Does Not Influence Influenza A Virus-Induced Disease Severity in Mice. AB - Influenza viruses are pathogens of significant public health importance. The influence of nutritional status on severity of disease has become increasingly recognized. In particular, high dietary salt intake has been linked to cardiovascular disease, but the effects on infectious diseases have not been studied. This study investigated the impact on influenza-induced morbidity and mortality in mice fed isocaloric diets containing 10-fold increments of sodium by altering the salt levels. Following infection, despite higher levels of IFN-gamma cytokine in the lung as well as virus-neutralizing antibody in the serum of mice fed the lowest salt level, the amounts of dietary salt intake had no substantial impact on the disease severity or the ability to respond immunologically to the infection. PMID- 26284686 TI - An Institutional Ethnography of Nurses' Support of Breastfeeding on the Night Shift. AB - OBJECTIVE: To describe nurses' support of breastfeeding on the night shift and to identify the interpersonal interactions and institutional structures that affect this support. DESIGN: Institutional ethnography. SETTING: The mother/baby unit of a tertiary care hospital with 4200 births per year. PARTICIPANTS: Registered nurses (N = 16) who provided care on the night shift to mother/infant dyads in the immediate postpartum period. METHODS: Data were collected using focus groups, individual and group interviews, and mother/baby unit observations. The focus groups were held before the night shift and had five participants. The nine individual and group interviews were conducted between 0100 and 0230 on the mother/baby unit. Three unit observations were conducted. Interviews were recorded, professionally transcribed, and analyzed using a content analysis method. RESULTS: Data analysis yielded three themes that described these nurses' support of breastfeeding on the night shift: competing priorities, incongruent expectations, and influential institutional structures. The need of visitors to see their new family members competed with the needs of mothers to rest and breastfeed their newborns. Helping breastfeeding dyads who experienced difficulties competed with providing care to other patients. Parents' expectations regarding newborn behavior were incongruent with the reality of newborn feeding and sleeping patterns. Institutional structures that affected the provision of breastfeeding support by nurses included hospital breastfeeding practices, staffing, and policies. CONCLUSION: Nurses' support of breastfeeding on the night shift encompasses a complex interplay of interpersonal interactions with new families and visitors regarding priorities and expectations and negotiating institutional structures such as feeding policies and staffing. PMID- 26284687 TI - New episodes of depression among Medicare beneficiaries with chronic obstructive pulmonary disease. AB - OBJECTIVES: Depression is a common comorbidity of chronic obstructive pulmonary disease (COPD) and is associated with increased exacerbations, healthcare utilization, and mortality. Among Medicare beneficiaries newly diagnosed with COPD, the objectives of this study were to (1) estimate the rate of new episodes of depression and (2) identify factors associated with depression. METHODS: We identified beneficiaries with a first diagnosis of COPD during 2006-2012 using a 5% random sample of Medicare administrative claims data by searching for ICD-9-CM codes 490, 491.x, 492.x, 494.x, or 496. We identified episodes of depression using ICD-9-CM codes 296.2x, 296.3x, and 311.xx. We calculated incidence rates and their 95% confidence intervals (95% CI) and used a discrete time analysis to identify factors associated with development of depression. RESULTS: Between 2006 and 2012, 125,348 beneficiaries meeting inclusion criteria were newly diagnosed with COPD. Twenty-three percent developed depression following COPD diagnosis. The annualized incidence rate of depression per 100 beneficiaries following COPD diagnosis was 9.4 (95% CI 9.3, 9.5). Rates were highest in the first 2 months following COPD diagnosis. COPD diagnosis was associated with increased risk of depression (risk ratio 1.76; 95% CI 1.73, 1.79) as were COPD-related hospitalizations (risk ratio 4.59; 95% CI 4.09, 5.15), a measure of COPD severity. CONCLUSIONS: Diagnosis of COPD increases the risk of depression. This study will aid in the allocation of resources to monitor and provide support for individuals with COPD at high risk of developing depression. PMID- 26284688 TI - Assessment of bolus transit with intraluminal impedance measurement in patients with esophageal motility disorders. AB - BACKGROUND: The clinical management of patients with non-obstructive dysphagia is notoriously difficult. Esophageal impedance measurement can be used to measure esophageal bolus transit without the use of radiation exposure to patients. However, validation of measurement of bolus transit with impedance monitoring has only been performed in healthy subjects with normal motility and not in patients with dysphagia and esophageal motility disorders. The aim was, therefore, to investigate the relationship between transit of swallowed liquid boluses in healthy controls and in patients with dysphagia. METHODS: Twenty healthy volunteers and 20 patients with dysphagia underwent concurrent impedance measurement and videofluoroscopy. Each subject swallowed five liquid barium boluses. The ability of detecting complete or incomplete bolus transit by means of impedance measurement was assessed, using radiographic bolus transit as the gold standard. KEY RESULTS: Impedance monitoring recognized stasis and transit in 80.5% of the events correctly, with 83.9% of bolus transit being recognized and 77.2% of stasis being recognized correctly. In controls 79.8% of all swallows were scored correctly, whereas in patients 81.3% of all swallows were scored correctly. Depending on the contractility pattern, between 77.0% and 94.3% of the swallows were scored correctly. CONCLUSIONS & INFERENCES: Impedance measurement can be used to assess bolus clearance patterns in healthy subjects, but can also be used to reliably assess bolus transit in patients with dysphagia and motility disorders. PMID- 26284689 TI - A Novel Inexpensive Use of Smartphone Technology for Ecological Momentary Assessment in Middle-Aged Women. AB - BACKGROUND: Commercially available mobile and Internet technologies present a promising opportunity to feasibly conduct ecological momentary assessment (EMA). The purpose of this study was to describe a novel EMA protocol administered on middle-aged women's smartphones via text messaging and mobile Internet. METHODS: Women (N = 9; mean age = 46.2 +/- 8.2 y) received 35 text message prompts to a mobile survey assessing activity, self-worth, and self-efficacy over 14 days. Prompts were scheduled and surveys were administered using commercial, Internet based programs. Prompting was tailored to each woman's daily wake/sleep schedule. Women concurrently wore a wrist-worn accelerometer. Feasibility was assessed via survey completion, accelerometer wear, participant feedback, and researcher notes. RESULTS: Of 315 prompted surveys, 287 responses were valid (91.1%). Average completion time was 1.52 +/- 1.03 minutes. One participant's activity data were excluded due to accelerometer malfunction, resulting in complete data from 8 participants (n = 252 [80.0%] valid observations). Women reported the survey was easily and quickly read/completed. However, most thought the accelerometer was inconvenient. CONCLUSIONS: High completion rates and perceived usability suggest capitalizing on widely available technology and tailoring prompting schedules may optimize EMA in middle-aged women. However, researchers may need to carefully select objective monitors to maintain data validity while limiting participant burden. PMID- 26284690 TI - Comparative Analysis of Human and Rodent Brain Primary Neuronal Culture Spontaneous Activity Using Micro-Electrode Array Technology. AB - Electrical activity in embryonic brain tissue has typically been studied using Micro Electrode Array (MEA) technology to make dozens of simultaneous recordings from dissociated neuronal cultures, brain stem cell progenitors, or brain slices from fetal rodents. Although these rodent neuronal primary culture electrical properties are mostly investigated, it has not been yet established to what extent the electrical characteristics of rodent brain neuronal cultures can be generalized to those of humans. A direct comparison of spontaneous spiking activity between rodent and human primary neurons grown under the same in vitro conditions using MEA technology has never been carried out before and will be described in the present study. Human and rodent dissociated fetal brain neuronal cultures were established in-vitro by culturing on a glass grid of 60 planar microelectrodes neurons under identical conditions. Three different cultures of human neurons were produced from tissue sourced from a single aborted fetus (at 16-18 gestational weeks) and these were compared with seven different cultures of embryonic rat neurons (at 18 gestational days) originally isolated from a single rat. The results show that the human and rodent cultures behaved significantly differently. Whereas the rodent cultures demonstrated robust spontaneous activation and network activity after only 10 days, the human cultures required nearly 40 days to achieve a substantially weaker level of electrical function. These results suggest that rat neuron preparations may yield inferences that do not necessarily transfer to humans. PMID- 26284691 TI - The use of rocuronium for ophthalmological surgery in an alpaca. PMID- 26284692 TI - Nature, timing, and severity of complications from ultrasound-guided percutaneous renal transplant biopsy. AB - We sought to review our kidney transplant biopsy experience to assess the incidence, type, presenting symptoms, and timing of renal transplant biopsy complications, as well as determine any modifiable risk factors for postbiopsy complications. This is an observational analysis of patients at the University of Wisconsin between January 1, 2000, and December 31, 2009. Patients with an INR >=1.5 or platelet counts less than 50 000 were not biopsied. An 18-gauge needle was used for biopsy. Over the study period, 3738 biopsies were performed with 66 complications (1.8%). No deaths occurred. A total of 0.7% were mild complications, 0.7% were moderate complications, 0.21% were severe complications, and 0.19% were life-threatening. Most complications occurred within the 4-h postbiopsy period, although serious complications were often delayed: 67% of complications requiring surgical intervention presented greater than 4 h after biopsy. Biopsy within 1 week of transplant had a 311% increased risk of a complication. Postbiopsy reduction in hematocrit and hemoglobin at 4 h was associated with a complication. In conclusion, life-threatening complications after renal allograft biopsy occurred in 0.19% of patients. Most complications occurred within 4 h postprocedure; however, many serious complications occurred with a time delay after initially uneventful monitoring. The only clinically significant laboratory predictor of a complication was a fall in the hematocrit or hemoglobin within 4 h. Patients biopsied within a week of transplant were at the highest risk for a complication and should therefore be most closely monitored. PMID- 26284694 TI - d-AO spherical aromaticity in Ce6O8. AB - After the first introduction of pi aromaticity in chemistry to explain the bonding, structure, and reactivity of benzene and its derivatives, this concept was further applied to many other compounds featuring other types of aromaticity (i.e., sigma, delta). Thus far, there have been no reports on d-AO-based spherical sigma aromaticity. Here, we predict a highly stable bare Ce6O8 cluster of a spherical shape using evolutionary algorithm USPEX and DFT + U calculations. Natural bond orbital analysis, adaptive natural density partitioning algorithm, electron localization function, and partial charge plots demonstrate that bare Ce6O8 cluster exhibits d-AO spherical sigma aromaticity, thus explaining its exotic geometry and stability. Ce6O8 complex plays an important role in many reactions and is known to exist in many forms, such as in NH4[Ce6(MU(3)O)5(MU(3)OH)3(MU(2)-C6H5COO)9(NO3)3(DMF)3]*DMF*H2O compound, which is prepared under room temperature, and acts as an oxidizing agent. PMID- 26284693 TI - Clinical features of pulmonary arterial hypertension in patients receiving dasatinib. AB - The prognosis of most leukemia patients treated with BCR-ABL tyrosine kinase inhibitors (TKIs) is favorable, and a more precise understanding of serious and potentially irreversible treatment-related toxicities is essential to properly inform treatment choice. Few cases of pulmonary arterial hypertension (PAH) have been reported in patients with leukemia treated with dasatinib, a second generation BCR-ABL TKI. To better understand characteristics and outcomes of dasatinib-treated patients with PAH, all clinical cases of PAH confirmed by right heart catheterization in the Bristol-Myers Squibb pharmacovigilance database (N = 41), including 22 previously unpublished cases, were examined for previous treatments for leukemia, patient characteristics, time to PAH onset, and outcomes. Our analysis shows that compared with PAH due to other etiologies, dasatinib-related PAH is atypical, in that it is associated with partial to complete reversibility upon treatment discontinuation. The incidence of dasatinib related PAH appears to be low. Most PAH cases were observed in patients who had received prior treatments for leukemia. No specific patient attributes appear to be associated with an increased risk of developing PAH while receiving dasatinib. Symptoms of PAH in dasatinib-treated leukemia patients should prompt a thorough workup, including consideration of confirmatory right-heart catheterization. In cases of confirmed PAH, dasatinib should be discontinued. PMID- 26284695 TI - Virus-induced gene silencing in Catharanthus roseus by biolistic inoculation of tobacco rattle virus vectors. AB - Catharanthus roseus constitutes the unique source of several valuable monoterpenoid indole alkaloids, including the antineoplastics vinblastine and vincristine. These alkaloids result from a complex biosynthetic pathway encompassing between 30 and 50 enzymatic steps whose characterisation is still underway. The most recent identifications of genes from this pathway relied on a tobacco rattle virus-based virus-induced gene silencing (VIGS) approach, involving an Agrobacterium-mediated inoculation of plasmids encoding the two genomic components of the virus. As an alternative, we developed a biolistic mediated approach of inoculation of virus-encoding plasmids that can be easily performed by a simple bombardment of young C. roseus plants. After optimisation of the transformation conditions, we showed that this approach efficiently silenced the phytoene desaturase gene, leading to strong and reproducible photobleaching of leaves. This biolistic transformation was also used to silence a previously characterised gene from the alkaloid biosynthetic pathway, encoding iridoid oxidase. Plant bombardment caused down-regulation of the targeted gene (70%), accompanied by a correlated decreased in MIA biosynthesis (45-90%), similar to results obtained via agro-transformation. Thus, the biolistic-based VIGS approach developed for C. roseus appears suitable for gene function elucidation and can readily be used instead of the Agrobacterium-based approach, e.g. when difficulties arise with agro-inoculations or when Agrobacterium-free procedures are required to avoid plant defence responses. PMID- 26284696 TI - Qualitative Research in Emergency Care Part I: Research Principles and Common Applications. AB - Qualitative methods are increasingly being used in emergency care research. Rigorous qualitative methods can play a critical role in advancing the emergency care research agenda by allowing investigators to generate hypotheses, gain an in depth understanding of health problems or specific populations, create expert consensus, and develop new intervention and dissemination strategies. This article, Part I of a two-article series, provides an introduction to general principles of applied qualitative health research and examples of its common use in emergency care research, describing study designs and data collection methods most relevant to our field, including observation, individual interviews, and focus groups. In Part II of this series, we will outline the specific steps necessary to conduct a valid and reliable qualitative research project, with a focus on interview-based studies. These elements include building the research team, preparing data collection guides, defining and obtaining an adequate sample, collecting and organizing qualitative data, and coding and analyzing the data. We also discuss potential ethical considerations unique to qualitative research as it relates to emergency care research. PMID- 26284697 TI - Inter-individual variation in weaning among rhesus macaques (Macaca mulatta): Serum stable isotope indicators of suckling duration and lactation. AB - Weaning is a transition in early development with major implications for infant survival and well-being, and for maternal lifetime reproductive success. The particular strategy a primate mother adopts in rearing her offspring represents a negotiation between her ability to invest and her need to invest, and can be considered adaptive and influenced by biological and social factors. Any investigation into how and why maternal weaning strategies differ among non-human primates is limited by the precision of the measurement tool used to assess infants' weaning ages. Stable carbon and nitrogen isotope analysis of soft tissues (e.g., hair, nails, feces, urine, blood) offers an objective means of monitoring the weaning status of infants. In this study, we assess stable isotope ratios in blood serum from 14 captive rhesus macaque dyads (Macaca mulatta) at infant ages 2, 5, 6, 7, 8, and 10 months to estimate the timing of weaning events. Male infants wean earlier than female infants. Infants with the lowest birth weights wean latest. Most infants wean upon reaching 2.5 times their birth weights, sooner than when weaning elsewhere has been predicted for captive cercopithecine primates. The longest weaning periods (ca. 10 months) are observed among infants of small mothers. The shortest weaning period, between 2 and 5 months, was among the lowest ranking dyad. Parity and mothers' ages had no discernible effect on the timing of weaning events. The stable carbon and nitrogen isotope values of dams during lactation are significantly different than those of a non-lactating adult female outgroup, raising questions about the suitability and selection of adult comparative baselines in studies where lactating mothers cannot be sampled longitudinally (e.g., bioarchaeology; paleontology). Am. J. Primatol. 78:1113-1134, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26284698 TI - To be or not to be? Mating success and survival trade-offs when switching between alternative reproductive tactics. AB - Hormones underlie the decision of assuming a territorial or a nonterritorial role, with territorial individuals usually having higher hormonal levels than nonterritorial individuals. As a territorial status is linked to higher mating opportunities, it is unclear why animals do not keep high hormonal levels and one explanation is that this would imply survival costs. We have tested this using males of the territorial damselfly Argia emma in the field. We increased juvenile hormone (JH) levels using methoprene in both territorial and nonterritorial males and predicted that: (i) males will keep (the case of territorial males) or become (the case of nonterritorial males) territorial after hormonal increase, and (ii) there will be an increase in mating success for nonterritorial males only and an impaired survival for both male tactics. Hormonally treated males remained or became territorial but had their survival impaired compared with control groups. Also, hormonally treated, ex-nonterritorial males increased their mating success compared with the other control, nonterritorial males. The reduced survival can be explained proximally by the energy devoted either to the enhanced aggression showed during territory defence or immune function (as detected previously in damselflies). Although nonterritorial males may increase their mating success by switching to a territorial tactic, they are possibly unable to do it naturally as JH is dietary dependent and usually nonterritorial animals are in poorer condition than territorial animals. PMID- 26284699 TI - Broad-Scale Evidence That pH Influences the Balance Between Microbial Iron and Sulfate Reduction. AB - Understanding basic controls on aquifer microbiology is essential to managing water resources and predicting impacts of future environmental change. Previous theoretical and laboratory studies indicate that pH can influence interactions between microorganisms that reduce ferric iron and sulfate. In this study, we test the environmental relevance of this relationship by examining broad-scale geochemical data from anoxic zones of aquifers. We isolated data from the U.S. Geological Survey National Water Information System for 19 principal aquifer systems. We then removed samples with chemical compositions inconsistent with iron- and sulfate-reducing environments and evaluated the relationships between pH and other geochemical parameters using Spearman's rho rank correlation tests. Overall, iron concentration and the iron-sulfide concentration ratio of groundwater share a statistically significant negative correlation with pH (P < 0.0001). These relationships indicate that the significance of iron reduction relative to sulfate reduction tends to increase with decreasing pH. Moreover, thermodynamic calculations show that, as the pH of groundwater decreases, iron reduction becomes increasingly favorable relative to sulfate reduction. Hence, the relative significance of each microbial reaction may vary in response to thermodynamic controls on microbial activity. Our findings demonstrate that trends in groundwater geochemistry across different regional aquifer systems are consistent with pH as a control on interactions between microbial iron and sulfate reduction. Environmental changes that perturb groundwater pH can affect water quality by altering the balance between these microbial reactions. PMID- 26284700 TI - Rational plasmid design and bioprocess optimization to enhance recombinant adeno associated virus (AAV) productivity in mammalian cells. AB - Viral vectors used for gene and oncolytic therapy belong to the most promising biological products for future therapeutics. Clinical success of recombinant adeno-associated virus (rAAV) based therapies raises considerable demand for viral vectors, which cannot be met by current manufacturing strategies. Addressing existing bottlenecks, we improved a plasmid system termed rep/cap split packaging and designed a minimal plasmid encoding adenoviral helper function. Plasmid modifications led to a 12-fold increase in rAAV vector titers compared to the widely used pDG standard system. Evaluation of different production approaches revealed superiority of processes based on anchorage- and serum-dependent HEK293T cells, exhibiting about 15-fold higher specific and volumetric productivity compared to well-established suspension cells cultivated in serum-free medium. As for most other viral vectors, classical stirred-tank bioreactor production is thus still not capable of providing drug product of sufficient amount. We show that manufacturing strategies employing classical surface-providing culture systems can be successfully transferred to the new fully-controlled, single-use bioreactor system Integrity(TM) iCELLis(TM) . In summary, we demonstrate substantial bioprocess optimizations leading to more efficient and scalable production processes suggesting a promising way for flexible large-scale rAAV manufacturing. PMID- 26284701 TI - Reaction of pyranose dehydrogenase from Agaricus meleagris with its carbohydrate substrates. AB - Monomeric Agaricus meleagris pyranose dehydrogenase (AmPDH) belongs to the glucose-methanol-choline family of oxidoreductases. An FAD cofactor is covalently tethered to His103 of the enzyme. AmPDH can double oxidize various mono- and oligosaccharides at different positions (C1 to C4). To study the structure/function relationship of selected active-site residues of AmPDH pertaining to substrate (carbohydrate) turnover in more detail, several active site variants were generated, heterologously expressed in Pichia pastoris, and characterized by biochemical, biophysical and computational means. The crystal structure of AmPDH shows two active-site histidines, both of which could take on the role as the catalytic base in the reductive half-reaction. Steady-state kinetics revealed that His512 is the only catalytic base because H512A showed a reduction in (kcat /KM )glucose by a factor of 10(5) , whereas this catalytic efficiency was reduced by two or three orders of magnitude for His556 variants (H556A, H556N). This was further corroborated by transient-state kinetics, where a comparable decrease in the reductive rate constant was observed for H556A, whereas the rate constant for the oxidative half-reaction (using benzoquinone as substrate) was increased for H556A compared to recombinant wild-type AmPDH. Steady-state kinetics furthermore indicated that Gln392, Tyr510, Val511 and His556 are important for the catalytic efficiency of PDH. Molecular dynamics (MD) simulations and free energy calculations were used to predict d-glucose oxidation sites, which were validated by GC-MS measurements. These simulations also suggest that van der Waals interactions are the main driving force for substrate recognition and binding. PMID- 26284703 TI - Microphthalmia-associated transcription factor regulates skin melanoblast migration by repressing the melanoma cell adhesion molecule. PMID- 26284706 TI - Les buveurs d'absinthe (The Absinthe Drinkers): Jean-Francois Raffaelli. PMID- 26284702 TI - Exome analysis of a family with Wolff-Parkinson-White syndrome identifies a novel disease locus. AB - Wolff-Parkinson-White (WPW) syndrome is a common cause of supraventricular tachycardia that carries a risk of sudden cardiac death. To date, mutations in only one gene, PRKAG2, which encodes the 5'-AMP-activated protein kinase subunit gamma-2, have been identified as causative for WPW. DNA samples from five members of a family with WPW were analyzed by exome sequencing. We applied recently designed prioritization strategies (VAAST/pedigree VAAST) coupled with an ontology-based algorithm (Phevor) that reduced the number of potentially damaging variants to 10: a variant in KCNE2 previously associated with Long QT syndrome was also identified. Of these 11 variants, only MYH6 p.E1885K segregated with the WPW phenotype in all affected individuals and was absent in 10 unaffected family members. This variant was predicted to be damaging by in silico methods and is not present in the 1,000 genome and NHLBI exome sequencing project databases. Screening of a replication cohort of 47 unrelated WPW patients did not identify other likely causative variants in PRKAG2 or MYH6. MYH6 variants have been identified in patients with atrial septal defects, cardiomyopathies, and sick sinus syndrome. Our data highlight the pleiotropic nature of phenotypes associated with defects in this gene. PMID- 26284707 TI - Coming Together on Long-term Care. PMID- 26284714 TI - The Global Health Implications of e-Cigarettes. PMID- 26284715 TI - Costs Associated With Using Different Insulin Preparations. PMID- 26284716 TI - A PIECE OF MY MIND. Writing the Wrong. PMID- 26284717 TI - e-Cigarette Use and Subsequent Tobacco Use by Adolescents: New Evidence About a Potential Risk of e-Cigarettes. PMID- 26284719 TI - Tinzaparin vs Warfarin for Treatment of Acute Venous Thromboembolism in Patients With Active Cancer: A Randomized Clinical Trial. AB - IMPORTANCE: Low-molecular-weight heparin is recommended over warfarin for the treatment of acute venous thromboembolism (VTE) in patients with active cancer largely based on results of a single, large trial. OBJECTIVE: To study the efficacy and safety of tinzaparin vs warfarin for treatment of acute, symptomatic VTE in patients with active cancer. DESIGN, SETTINGS, AND PARTICIPANTS: A randomized, open-label study with blinded central adjudication of study outcomes enrolled patients in 164 centers in Asia, Africa, Europe, and North, Central, and South America between August 2010 and November 2013. Adult patients with active cancer (defined as histologic diagnosis of cancer and receiving anticancer therapy or diagnosed with, or received such therapy, within the previous 6 months) and objectively documented proximal deep vein thrombosis (DVT) or pulmonary embolism, with a life expectancy greater than 6 months and without contraindications for anticoagulation, were followed up for 180 days and for 30 days after the last study medication dose for collection of safety data. INTERVENTIONS: Tinzaparin (175 IU/kg) once daily for 6 months vs conventional therapy with tinzaparin (175 IU/kg) once daily for 5 to 10 days followed by warfarin at a dose adjusted to maintain the international normalized ratio within the therapeutic range (2.0-3.0) for 6 months. MAIN OUTCOMES AND MEASURES: Primary efficacy outcome was a composite of centrally adjudicated recurrent DVT, fatal or nonfatal pulmonary embolism, and incidental VTE. Safety outcomes included major bleeding, clinically relevant nonmajor bleeding, and overall mortality. RESULTS: Nine hundred patients were randomized and included in intention-to-treat efficacy and safety analyses. Recurrent VTE occurred in 31 of 449 patients treated with tinzaparin and 45 of 451 patients treated with warfarin (6-month cumulative incidence, 7.2% for tinzaparin vs 10.5% for warfarin; hazard ratio [HR], 0.65 [95% CI, 0.41-1.03]; P = .07). There were no differences in major bleeding (12 patients for tinzaparin vs 11 patients for warfarin; HR, 0.89 [95% CI, 0.40 1.99]; P = .77) or overall mortality (150 patients for tinzaparin vs 138 patients for warfarin; HR, 1.08 [95% CI, 0.85-1.36]; P = .54). A significant reduction in clinically relevant nonmajor bleeding was observed with tinzaparin (49 of 449 patients for tinzaparin vs 69 of 451 patients for warfarin; HR, 0.58 [95% CI, 0.40-0.84]; P = .004). CONCLUSIONS AND RELEVANCE: Among patients with active cancer and acute symptomatic VTE, the use of full-dose tinzaparin (175 IU/kg) daily compared with warfarin for 6 months did not significantly reduce the composite measure of recurrent VTE and was not associated with reductions in overall mortality or major bleeding, but was associated with a lower rate of clinically relevant nonmajor bleeding. Further studies are needed to assess whether the efficacy outcomes would be different in patients at higher risk of recurrent VTE. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130025. PMID- 26284721 TI - Association of Electronic Cigarette Use With Initiation of Combustible Tobacco Product Smoking in Early Adolescence. AB - IMPORTANCE: Exposure to nicotine in electronic cigarettes (e-cigarettes) is becoming increasingly common among adolescents who report never having smoked combustible tobacco. OBJECTIVE: To evaluate whether e-cigarette use among 14-year old adolescents who have never tried combustible tobacco is associated with risk of initiating use of 3 combustible tobacco products (ie, cigarettes, cigars, and hookah). DESIGN, SETTING, AND PARTICIPANTS: Longitudinal repeated assessment of a school-based cohort at baseline (fall 2013, 9th grade, mean age = 14.1 years) and at a 6-month follow-up (spring 2014, 9th grade) and a 12-month follow-up (fall 2014, 10th grade). Ten public high schools in Los Angeles, California, were recruited through convenience sampling. Participants were students who reported never using combustible tobacco at baseline and completed follow-up assessments at 6 or 12 months (N = 2530). At each time point, students completed self-report surveys during in-classroom data collections. EXPOSURE: Student self-report of whether he or she ever used e-cigarettes (yes or no) at baseline. MAIN OUTCOMES AND MEASURES: Six- and 12-month follow-up reports on use of any of the following tobacco products within the prior 6 months: (1) any combustible tobacco product (yes or no); (2) combustible cigarettes (yes or no), (3) cigars (yes or no); (4) hookah (yes or no); and (5) number of combustible tobacco products (range: 0-3). RESULTS: Past 6-month use of any combustible tobacco product was more frequent in baseline e-cigarette ever users (n = 222) than never users (n = 2308) at the 6 month follow-up (30.7% vs 8.1%, respectively; difference between groups in prevalence rates, 22.7% [95% CI, 16.4%-28.9%]) and at the 12-month follow-up (25.2% vs 9.3%, respectively; difference between groups, 15.9% [95% CI, 10.0% 21.8%]). Baseline e-cigarette use was associated with greater likelihood of use of any combustible tobacco product averaged across the 2 follow-up periods in the unadjusted analyses (odds ratio [OR], 4.27 [95% CI, 3.19-5.71]) and in the analyses adjusted for sociodemographic, environmental, and intrapersonal risk factors for smoking (OR, 2.73 [95% CI, 2.00-3.73]). Product-specific analyses showed that baseline e-cigarette use was positively associated with combustible cigarette (OR, 2.65 [95% CI, 1.73-4.05]), cigar (OR, 4.85 [95% CI, 3.38-6.96]), and hookah (OR, 3.25 [95% CI, 2.29-4.62]) use and with the number of different combustible products used (OR, 4.26 [95% CI, 3.16-5.74]) averaged across the 2 follow-up periods. CONCLUSIONS AND RELEVANCE: Among high school students in Los Angeles, those who had ever used e-cigarettes at baseline compared with nonusers were more likely to report initiation of combustible tobacco use over the next year. Further research is needed to understand whether this association may be causal. PMID- 26284720 TI - Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes: The SCALE Diabetes Randomized Clinical Trial. AB - IMPORTANCE: Weight loss of 5% to 10% can improve type 2 diabetes and related comorbidities. Few safe, effective weight-management drugs are currently available. OBJECTIVE: To investigate efficacy and safety of liraglutide vs placebo for weight management in adults with overweight or obesity and type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: Fifty-six-week randomized (2:1:1), double-blind, placebo-controlled, parallel-group trial with 12-week observational off-drug follow-up period. The study was conducted at 126 sites in 9 countries between June 2011 and January 2013. Of 1361 participants assessed for eligibility, 846 were randomized. Inclusion criteria were body mass index of 27.0 or greater, age 18 years or older, taking 0 to 3 oral hypoglycemic agents (metformin, thiazolidinedione, sulfonylurea) with stable body weight, and glycated hemoglobin level 7.0% to 10.0%. INTERVENTIONS: Once-daily, subcutaneous liraglutide (3.0 mg) (n = 423), liraglutide (1.8 mg) (n = 211), or placebo (n = 212), all as adjunct to 500 kcal/d dietary deficit and increased physical activity (>=150 min/wk). MAIN OUTCOMES AND MEASURES: Three coprimary end points: relative change in weight, proportion of participants losing 5% or more, or more than 10%, of baseline weight at week 56. RESULTS: Baseline weight was 105.7 kg with liraglutide (3.0-mg dose), 105.8 kg with liraglutide (1.8-mg dose), and 106.5 kg with placebo. Weight loss was 6.0% (6.4 kg) with liraglutide (3.0-mg dose), 4.7% (5.0 kg) with liraglutide (1.8-mg dose), and 2.0% (2.2 kg) with placebo (estimated difference for liraglutide [3.0 mg] vs placebo, -4.00% [95% CI, -5.10% to -2.90%]; liraglutide [1.8 mg] vs placebo, -2.71% [95% CI, -4.00% to -1.42%]; P < .001 for both). Weight loss of 5% or greater occurred in 54.3% with liraglutide (3.0 mg) and 40.4% with liraglutide (1.8 mg) vs 21.4% with placebo (estimated difference for liraglutide [3.0 mg] vs placebo, 32.9% [95% CI, 24.6% to 41.2%]; for liraglutide [1.8 mg] vs placebo, 19.0% [95% CI, 9.1% to 28.8%]; P < .001 for both). Weight loss greater than 10% occurred in 25.2% with liraglutide (3.0 mg) and 15.9% with liraglutide (1.8 mg) vs 6.7% with placebo (estimated difference for liraglutide [3.0 mg] vs placebo, 18.5% [95% CI, 12.7% to 24.4%], P < .001; for liraglutide [1.8 mg] vs placebo, 9.3% [95% CI, 2.7% to 15.8%], P = .006). More gastrointestinal disorders were reported with liraglutide (3.0 mg) vs liraglutide (1.8 mg) and placebo. No pancreatitis was reported. CONCLUSIONS AND RELEVANCE: Among overweight and obese participants with type 2 diabetes, use of subcutaneous liraglutide (3.0 mg) daily, compared with placebo, resulted in weight loss over 56 weeks. Further studies are needed to evaluate longer-term efficacy and safety. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT01272232. PMID- 26284722 TI - Septic Shock: Advances in Diagnosis and Treatment. AB - IMPORTANCE: Septic shock is a clinical emergency that occurs in more than 230,000 US patients each year. OBSERVATIONS AND ADVANCES: In the setting of suspected or documented infection, septic shock is typically defined in a clinical setting by low systolic (<=90 mm Hg) or mean arterial blood pressure (<=65 mm Hg) accompanied by signs of hypoperfusion (eg, oliguria, hyperlactemia, poor peripheral perfusion, or altered mental status). Focused ultrasonography is recommended for the prompt recognition of complicating physiology (eg, hypovolemia or cardiogenic shock), while invasive hemodynamic monitoring is recommended only for select patients. In septic shock, 3 randomized clinical trials demonstrate that protocolized care offers little advantage compared with management without a protocol. Hydroxyethyl starch is no longer recommended, and debate continues about the role of various crystalloid solutions and albumin. CONCLUSIONS AND RELEVANCE: The prompt diagnosis of septic shock begins with obtainment of medical history and performance of a physical examination for signs and symptoms of infection and may require focused ultrasonography to recognize more complex physiologic manifestations of shock. Clinicians should understand the importance of prompt administration of intravenous fluids and vasoactive medications aimed at restoring adequate circulation, and the limitations of protocol-based therapy, as guided by recent evidence. PMID- 26284723 TI - Nicotine Replacement Therapy as a Maintenance Treatment. PMID- 26284724 TI - Isotonic vs Hypotonic Intravenous Fluids for Hospitalized Children. AB - CLINICAL QUESTION: Is isotonic fluid associated with a lower incidence of hyponatremia when compared with hypotonic fluid for maintenance intravenous fluid therapy in children? BOTTOM LINE: Compared with hypotonic fluid, isotonic fluid is associated with a lower incidence of hyponatremia, without evidence of an increase in adverse outcomes. PMID- 26284725 TI - Sacubitril/Valsartan (Entresto) for Heart Failure. PMID- 26284726 TI - Inferior Vena Cava Filter and Recurrent Pulmonary Embolism. PMID- 26284727 TI - Inferior Vena Cava Filter and Recurrent Pulmonary Embolism--Reply. PMID- 26284728 TI - Common Cold Treatment Using Zinc. PMID- 26284729 TI - Common Cold Treatment Using Zinc--Reply. PMID- 26284731 TI - Incorrect Dose in Figure. PMID- 26284730 TI - Wording Errors in the Text. PMID- 26284733 TI - Of Science, Humanism, and Medicine. PMID- 26284734 TI - JAMA PATIENT PAGE. Specific Medications for Weight Loss. PMID- 26284735 TI - Batf3 deficiency proves the pivotal role of CD8alpha+ dendritic cells in protection induced by vaccination with attenuated Plasmodium sporozoites. AB - Increasing evidence indicates that hepatic CD8alpha+ dendritic cells (DCs) are important antigen cross-presenting cells (APC) involved in the priming of protective CD8+ T-cell responses induced by live-attenuated Plasmodium sporozoites. Experimental proof for a critical role of CD8alpha+ DCs in protective pre-erythrocytic malaria immunizations has pivotal implications for vaccine development, including improved vectored subunit vaccines. Employing Batf3-/- mice, which lack functional CD8alpha+ DCs, we demonstrate that deficiency of these particular APCs completely abolishes protection and corresponding signatures of vaccine-induced immunity. We show that in wild-type, but not in Batf3-/- , mice CD8alpha+ DCs accumulate in the liver after immunization with live irradiation-attenuated P. berghei sporozoites. IFN-gamma production by Plasmodium antigen-specific CD8+ T cells is dependent on functional Batf3. In addition, our results demonstrate that the dysfunctional cDC-CD8+ T cell axis correlates with MHC class II upregulation on splenic CD8alpha- DCs. Collectively, these findings underscore the essential role of CD8alpha+ DCs in robust protection induced by experimental live-attenuated malaria vaccines. PMID- 26284736 TI - Pyrolytic Treatment and Fertility Enhancement of Soils Contaminated with Heavy Hydrocarbons. AB - Pyrolysis of contaminated soils at 420 degrees C converted recalcitrant heavy hydrocarbons into "char" (a carbonaceous material similar to petroleum coke) and enhanced soil fertility. Pyrolytic treatment reduced total petroleum hydrocarbons (TPH) to below regulatory standards (typically <1% by weight) within 3 h using only 40-60% of the energy required for incineration at 600-1200 degrees C. Formation of polycyclic aromatic hydrocarbons (PAHs) was not observed, with post pyrolysis levels well below applicable standards. Plant growth studies showed a higher biomass production of Arabidopsis thaliana and Lactuca sativa (Simpson black-seeded lettuce) (80-900% heavier) in pyrolyzed soils than in contaminated or incinerated soils. Elemental analysis showed that pyrolyzed soils contained more carbon than incinerated soils (1.4-3.2% versus 0.3-0.4%). The stark color differences between pyrolyzed and incinerated soils suggest that the carbonaceous material produced via pyrolysis was dispersed in the form of a layer coating the soil particles. Overall, these results suggest that soil pyrolysis could be a viable thermal treatment to quickly remediate soils impacted by weathered oil while improving soil fertility, potentially enhancing revegetation. PMID- 26284737 TI - Peripheral Blood Mononuclear Cells Spontaneous Osteoclastogenesis: Mechanisms Driving the Process and Clinical Relevance in Skeletal Disease. AB - In vitro peripheral blood mononuclear cells differentiate into osteoclasts under the influence of osteoclast-stimulating factors. However, accumulating evidence suggests spontaneous osteoclasts formation and activity in patients affected by local or systemic bone remodeling diseases in comparison with healthy controls. Therefore, within this review, we summarize the studies where spontaneous osteoclastogenesis of peripheral blood mononuclear cells was observed in pathological conditions of the skeletal system. We indicate a linkage between immunoregulation by T cells and spontaneous osteoclasts formation with increased levels of tumor necrosis factors-alpha, receptor activator of nuclear factor kappa-B ligand and inteleukin-7 production. In the light of these results, it would be of crucial importance to deepen the correlation between systemic bone remodeling diseases and spontaneous osteoclastogenesis as well as to investigate in detail the mechanisms underlying this phenomenon and the clinical relevance in bone remodeling disease diagnosis and monitoring. PMID- 26284738 TI - Reproductive mode and the shifting arenas of evolutionary conflict. AB - In sexually reproducing organisms, the genetic interests of individuals are not perfectly aligned. Conflicts among family members are prevalent since interactions involve the transfer of limited resources between interdependent players. Intrafamilial conflict has traditionally been considered along three major axes: between the sexes, between parents and offspring, and between siblings. In these interactions, conflict is expected over traits in which the resulting phenotypic value is determined by multiple family members who have only partially overlapping fitness optima. We focus on four major categories of animal reproductive mode (broadcast spawning, egg laying, live bearing, and live bearing with matrotrophy) and identify the shared phenotypes or traits over which conflict is expected, and then review the empirical literature for evidence of their occurrence. Major transitions among reproductive mode, such as a shift from external to internal fertilization, an increase in egg-retention time, modifications of embryos and mothers for nutrient transfer, the evolution of postnatal parental care, and increased interaction with the kin network, mark key shifts that both change and expand the arenas in which conflict is played out. PMID- 26284739 TI - Editorial transition at Alzheimer's Disease and Associated Disorders. PMID- 26284741 TI - Multiscale Assembly of Grape-Like Ferroferric Oxide and Carbon Nanotubes: A Smart Absorber Prototype Varying Temperature to Tune Intensities. AB - Ideal electromagnetic attenuation material should not only shield the electromagnetic interference but also need strong absorption. Lightweight microwave absorber with thermal stability and high efficiency is a highly sought after goal of researchers. Tuning microwave absorption to meet the harsh requirements of thermal environments has been a great challenge. Here, grape-like Fe3O4-multiwalled carbon nanotubes (MWCNTs) are synthesized, which have unique multiscale-assembled morphology, relatively uniform size, good crystallinity, high magnetization, and favorable superparamagnetism. The Fe3O4-MWCNTs is proven to be a smart microwave-absorber prototype with tunable high intensities in double belts in the temperature range of 323-473 K and X band. Maximum absorption in two absorbing belts can be simultaneously tuned from ~-10 to ~-15 dB and from ~-16 to ~-25 dB by varying temperature, respectively. The belt for reflection loss <=-20 dB can almost cover the X band at 323 K. The tunable microwave absorption is attributed to effective impedance matching, benefiting from abundant interfacial polarizations and increased magnetic loss resulting from the grape-like Fe3O4 nanocrystals. Temperature adjusts the impedance matching by changing both the dielectric and magnetic loss. The special assembly of MWCNTs and magnetic loss nanocrystals provides an effective pathway to realize excellent absorbers at elevated temperature. PMID- 26284740 TI - Description of 214 cases of autoimmune congenital heart block: Results of the French neonatal lupus syndrome. AB - BACKGROUND: Cardiac neonatal lupus syndrome is due to anti-SSA or SSB antibodies and mainly includes congenital heart block (CHB) and dilated cardiomyopathy (DCM). Its optimal management is still debated. We report a large series of autoimmune high degree CHB. METHODS: Inclusion criteria in this retrospective study were fetuses or neonates with high-degree CHB associated with maternal anti SSA/SSB antibodies. RESULTS: 214 CHB were included: 202 detected in utero at a median term of 23 weeks' gestation (WG) [range 16 to 39 WG] and 12 neonatal cases diagnosed at a median age of 0 days [range birth to 8 days]. The 214 cases of CHB included 202 (94.4%) third-degree CHB, 8 (3.7%) second-degree CHB, and 4 (1.9%) intermittent CHB. In multivariate analysis, the factors associated with feto neonatal deaths (15.7%) were hydrops (p<0.001; hazard ratio [HR] 12.4 [95% confidence interval (95%CI) 4.7-32.7]) and prematurity (p=0.002; HR 17.1 [95%CI 2.8-103.1]). During a median follow-up of 7 years [birth to 36 years], 148 of 187 children born alive (79.1%) had a pacemaker, 35 (18.8%, one missing data) had DCM, and 22 (11.8%) died. In multivariate analysis, factors associated with child death were in utero DCM (p=0.0157; HR 6.37 [95%CI: 1.25-32.44]), postnatal DCM (p<0.0001; HR 227.58[95%CI: 24.33-2128.46]) and pacemaker implantation (p=0.0035; HR 0.11[95%CI: 0.02-0.51]). The use of fluorinated steroids was neither associated with survival nor with regression of 2nd degree CHB. CONCLUSION: In this second largest series of CHB, we confirm some of the previous results. We were unable to find data supporting the routine use of in utero fluorinated steroids. PMID- 26284743 TI - Endoscopic mucosal ablation and over-the-scope clipping for fistula closure. PMID- 26284742 TI - Third trimester-equivalent ethanol exposure increases anxiety-like behavior and glutamatergic transmission in the basolateral amygdala. AB - Ethanol consumption during pregnancy produces a wide range of morphological and behavioral alterations known as fetal alcohol spectrum disorder (FASD). Among the behavioral deficits associated with FASD is an increased probability of developing anxiety disorders. Studies with animal models of FASD have demonstrated that ethanol exposure during the equivalent to the 1(st) and 2(nd) trimesters of human pregnancy increases anxiety-like behavior. Here, we examined the impact on this type of behavior of exposure to high doses of ethanol in vapor inhalation chambers during the rat equivalent to the human 3rd trimester of pregnancy (i.e., neonatal period in these animals). We evaluated anxiety-like behavior with the elevated plus maze. Using whole-cell patch-clamp electrophysiological techniques in brain slices, we also characterized glutamatergic and GABAergic synaptic transmission in the basolateral amygdala, a brain region that has been implicated to play a role in emotional behavior. We found that ethanol-exposed adolescent offspring preferred the closed arms over the open arms in the elevated plus maze and displayed lower head dipping activity than controls. Electrophysiological measurements showed an increase in the frequency of spontaneous and miniature excitatory postsynaptic currents in pyramidal neurons from the ethanol group. These findings suggest that high-dose ethanol exposure during the equivalent to the last trimester of human pregnancy can persistently increase excitatory synaptic inputs to principal neurons in the basolateral amygdala, leading to an increase in anxiety-like behaviors. PMID- 26284744 TI - Endoscopic closure of iatrogenic duodenal perforation using dual over-the-scope clips. PMID- 26284745 TI - Seeking everyday wellbeing: The coast as a therapeutic landscape. AB - Recent research suggests coastal environments may promote human health and wellbeing. This article explores the diverse coastal experiences sought out by residents of two towns in south west England to promote and preserve their personal wellbeing in the context of their everyday lives. It draws on the findings of an in-depth interpretive study conducted from May to November 2013 that examined the relative contribution of varied green and blue space experiences to individual wellbeing through the life course. Personalised activity maps produced using accelerometer and Global Positioning System (GPS) data were used to guide in-depth geo-narrative interviews with a purposive sample of 33 participants. This was combined with a subset of nine case study go-along interviews in places deemed therapeutic by the participants themselves, offering deeper insight into the lived experiences and relationships playing out within such places. Situated in a novel adaptation of the therapeutic landscapes framework, this article explores how symbolic, achievement-oriented, immersive and social experiences contributed to participants' sense of wellbeing in their local coastal areas. Participants expressed particularly strong and often enduring connections to the local coastline, with different coastal stretches perceived to cater for varied therapeutic needs and interests, at multiple scales and intensities. The findings suggest the need for greater acknowledgement of people's emotional, deeply embodied and often shared connections to the coast within coastal management policy and practice, both nationally and internationally. Importantly, such efforts should recognise the fluid, dynamic nature of this land-sea boundary, and the valued therapeutic experiences linked to this fluidity. PMID- 26284746 TI - Spectral-Domain Optical Coherence Tomography in Wagner Syndrome: Characterization of Vitreoretinal Interface and Foveal Changes. AB - PURPOSE: To evaluate the spectrum of morphologic abnormalities in patients with Wagner syndrome by spectral-domain optical coherence tomography (SD OCT). DESIGN: Retrospective comparative case study. METHODS: Institutional study of patients entered into the French Vitreoretinopathy Study Group database. Twelve eyes of 9 patients from 3 unrelated families with genetically confirmed Wagner syndrome and 28 eyes from 15 age- and sex-matched healthy family controls were scanned by SD OCT. Morphology and layer thickness of the total retina, inner retinal layers, outer retinal layers, and photoreceptor layer at different degrees of eccentricity from the fovea were compared between the 2 groups. RESULTS: A thick multilayered membrane adherent to the perifovea but completely detached from the fovea, thus forming a bridge over the foveal pit, was observed in 84% of eyes from patients with Wagner syndrome. At the equatorial area, SD OCT imaging allowed visualization of the architecture of an avascular vitreous veil with localized retinal traction. Most retinal layers were significantly thinner in patients with Wagner syndrome compared to the control group, except at the foveal center where abnormal persistence of 1 or more inner retinal layers could be observed. CONCLUSION: SD OCT provides better structural insight into the range of retinal defects at the vitreoretinal interface and fovea, which is not only useful for improving diagnosis and management, but also for understanding the pathogenesis of Wagner syndrome. PMID- 26284747 TI - Safety of Spectacles for Children's Vision: A Cluster-Randomized Controlled Trial. AB - PURPOSE: To study safety of children's glasses in rural China, where fear that glasses harm vision is an important barrier for families and policy makers. DESIGN: Exploratory analysis from a cluster-randomized, investigator-masked, controlled trial. METHODS: Among primary schools (n = 252) in western China, children were randomized by school to 1 of 3 interventions: free glasses provided in class, vouchers for free glasses at a local facility, or glasses prescriptions only (Control group). The main outcome of this analysis is uncorrected visual acuity after 8 months, adjusted for baseline acuity. RESULTS: Among 19 934 children randomly selected for screening, 5852 myopic (spherical equivalent refractive error <=-0.5 diopters) eyes of 3001 children (14.7%, mean age 10.5 years) had VA <=6/12 without glasses correctable to >6/12 with glasses, and were eligible. Among these, 1903 (32.5%), 1798 (30.7%), and 2151 (36.8%) were randomized to Control, Voucher, and Free Glasses, respectively. Intention-to treat analyses were performed on all 1831 (96.2%), 1699 (94.5%), and 2007 (93.3%) eyes of children with follow-up in Control, Voucher, and Free Glasses groups. Final visual acuity for eyes of children in the treatment groups (Free Glasses and Voucher) was significantly better than for Control children, adjusting only for baseline visual acuity (difference of 0.023 logMAR units [0.23 vision chart lines, 95% CI: 0.03, 0.43]) or for other baseline factors as well (0.025 logMAR units [0.25 lines, 95% CI 0.04, 0.45]). CONCLUSION: We found no evidence that spectacles promote decline in uncorrected vision with aging among children. PMID- 26284748 TI - Treatment of depression in patients with temporal lobe epilepsy: A pilot study of cognitive behavioral therapy vs. selective serotonin reuptake inhibitors. AB - There is a high prevalence of depression in patients with epilepsy, which negatively impacts their quality of life (QOL) and seizure control. Currently, the first-line of treatment for depression in patients with epilepsy is based on selective serotonin reuptake inhibitors (SSRIs). The main objective of this pilot study was to compare cognitive behavioral therapy (CBT) versus SSRIs for the treatment of major depressive disorder (MDD) in patients with temporal lobe epilepsy (TLE). Seven patients who received group CBT were compared with eight patients treated with SSRIs. All were diagnosed with MDD and TLE. Patients were assessed at baseline before treatment and at six and 12weeks during treatment with the Quality of Life in Epilepsy Scale of 31 items (QOLIE 31), the Beck Depression Inventory (BDI), and the Hospital Anxiety and Depression Scale (HADS). Seizure records were also taken on a monthly basis. After 12weeks of treatment, both groups showed improved QOL and reduced severity of depression symptoms. There were no statistically significant group differences in the final scores for the BDI (p=0.40) and QOLIE 31 (p=0.72), although the effect size on QOL was higher for the group receiving CBT. In conclusion, the present study suggests that both CBT and SSRIs may improve MDD and QOL in patients with TLE. We found no significant outcome differences between both treatment modalities. These findings support further study using a double-blind controlled design to demonstrate the efficacy of CBT and SSRIs in the treatment of MDD and QOL in patients with TLE. PMID- 26284749 TI - Copper-Catalyzed Aerobic Oxidative Dehydrogenative Formal [2 + 3] Cyclization of Glycine Esters with alpha-Angelicalactone: Approach To Construct Polysubstituted Pyrrolidones. AB - A novel and efficient copper-catalyzed aerobic oxidative dehydrogenative formal [2 + 3] cyclization of glycine derivatives with alpha-angelicalactone is described. A series of complex pyrrolidones were produced under mild and simple reaction conditions. PMID- 26284750 TI - Physiological adaptation of growth kinetics in activated sludge. AB - Physiological adaptation as it occurs in bacterial cells at variable environmental conditions influences characteristic properties of growth kinetics significantly. However, physiological adaptation to growth related parameters in activated sludge modelling is not yet recognised. Consequently these parameters are regarded to be constant. To investigate physiological adaptation in activated sludge the endogenous respiration in an aerobic degradation batch experiment and simultaneous to that the maximum possible respiration in an aerobic growth batch experiment was measured. The activated sludge samples were taken from full scale wastewater treatment plants with different sludge retention times (SRTs). It could be shown that the low SRT sludge adapts by growth optimisation (high maximum growth rate and high decay rate) to its particular environment where a high SRT sludge adapts by survival optimization (low maximum growth rate and low decay rate). Thereby, both the maximum specific growth rate and the decay rate vary in the same pattern and are strongly correlated to each other. To describe the physiological state of mixed cultures like activated sludge quantitatively a physiological state factor (PSF) is proposed as the ratio of the maximum specific growth rate and the decay rate. The PSF can be expressed as an exponential function with respect to the SRT. PMID- 26284751 TI - Motor Cortex Inhibition is Increased During a Secondary Cognitive Task. AB - The purpose of this study was to assess the effect of a cognitive task on motor cortex excitability and inhibition. Transcranial magnetic stimulation of the motor cortex was performed on 20 healthy individuals (18-24 years; 9 females) to measure motor evoked potentials (MEPs) and cortical silent periods at baseline, during, and following a secondary cognitive task. The MEP amplitude increased from 0.50 +/- 0.09-0.87 +/- 0.50 mV during a secondary cognitive task (p = .04), and returned to baseline (0.48 +/- 0.31 mV; p = .90) posttask. The CSP duration also increased from 93.48 +/- 28.76-113.6 +/- 33.68 ms (p = .001) during the cognitive task, and returned to baseline posttask (89.0 +/- 6.9 ms; p = .88). In the presence of a cognitive task, motor cortex excitability and inhibition were both increased relative to baseline. The increase in inhibition may help to explain the motor deficits experienced while performing a secondary cognitive task. PMID- 26284752 TI - Mechanism of Polysulfone-Based Anion Exchange Membranes Degradation in Vanadium Flow Battery. AB - The stability of hydrocarbon ion exchange membranes is one of the critical issues for a flow battery. However, the degradation mechanism of ion exchange membranes has been rarely investigated especially for anion exchange membranes. Here, the degradation mechanism of polysulfone based anion exchange membranes, carrying pyridine ion exchange groups, under vanadium flow battery (VFB) medium was investigated in detail. We find that sp(2) hybrid orbital interactions between pyridinic-nitrogen in 4,4'-bipyridine and benzylic carbon disrupt the charge state balance of pristine chloromethylated polysulfone. This difference in electronegativity inversely induces an electrophilic carbon center in the benzene ring, which can be attacked by the lone pair electron on the vanadium(V) oxygen species, further leading to the degradation of polymer backbone, while leaving the 4,4'-bipyridine ion exchange groups stable. This work represents a step toward design and construction of alternative type of chemically stable hydrocarbon ion exchange membranes for VFB. PMID- 26284754 TI - Modern Organic Synthesis with alpha-Diazocarbonyl Compounds. PMID- 26284753 TI - Clotting Mimicry from Robust Hemostatic Bandages Based on Self-Assembling Peptides. AB - Uncontrolled bleeding from traumatic wounds is a major factor in deaths resulting from military conflict, accidents, disasters and crime. Self-assembling peptide nanofibers have shown superior hemostatic activity, and herein, we elucidate their mechanism by visualizing the formation of nanofiber-based clots that aggregate blood components with a similar morphology to fibrin-based clots. Furthermore, to enhance its direct application to a wound, we developed layer-by layer assembled thin film coatings onto common materials used for wound dressings gauze and gelatin sponges. We find these nanofibers elute upon hydration under physiological conditions and generate nanofiber-based clots with blood. After exposure to a range of harsh temperature conditions (-80 to 60 degrees C) for a week and even 5 months at 60 degrees C, these hemostatic bandages remain capable of releasing active nanofibers. In addition, the application of these nanofiber based films from gauze bandages was found to accelerate hemostasis in porcine skin wounds as compared to plain gauze. The thermal robustness, in combination with the self-assembling peptide's potent hemostatic activity, biocompatibility, biodegradability, and low cost of production, makes this a promising approach for a cheap yet effective hemostatic bandage. PMID- 26284755 TI - Evaluation of dehiscence and fenestration in adolescent patients affected by unilateral cleft lip and palate: A retrospective cone beam computed tomography study. AB - OBJECTIVE: To evaluate the presence of dehiscence and fenestration defects around anterior teeth in the cleft region and to compare these findings with the noncleft side in the same patients using cone beam computed tomography (CBCT). MATERIALS AND METHODS: CBCT scans of 44 patients (26 males, 18 females; mean age, 14.04 +/- 3.81 years) with unilateral cleft lip and palate (UCLP) were assessed to define dehiscences and fenestrations of the anterior teeth in both cleft and noncleft sides of the UCLP patients and a control group of noncleft patients (51 patients; 21 males, 30 females; mean age, 14.52 +/- 1.16 years). Data were analyzed using Pearson's chi(2) and Student's t-test. RESULTS: The prevalence of dehiscences at the maxillary central incisors, lateral incisors, and canines teeth were 43.2%, 70.6%, and 34.1% on the cleft side and 22.7%, 53.1%, and 27.3% on the noncleft side of UCLP patients, and 13.7%, 7.8%, and 13.7% in controls, respectively (statistically no difference between the sides of cleft patients). The cleft patients had a statistically significantly higher prevalence of dehiscences than did the controls on both the cleft and noncleft sides (P < .05), except for the maxillary central incisors. Fenestrations for these teeth were significantly more common on the cleft side in UCLP patients compared with controls (P < .05), whereas the difference for maxillary lateral incisors was not statistically significant. CONCLUSIONS: Patients with UCLP showed a higher prevalence of dehiscence and fenestration defects around the maxillary anterior teeth. PMID- 26284756 TI - Optimization of preparation process of activated carbon from chestnut burs assisted by microwave and pore structural characterization analysis. AB - In this study, activated carbon was prepared from Chinese chestnut burs assisted by microwave irradiation with potassium hydroxide (KOH) as activator, and the process conditions were optimized employing Box-Behnken design (BBD) and response surface methodology (RSM). The optimized variables were irradiation time, impregnation time, and mass ratio of alkali-to-carbon, and the iodine adsorption value was used to evaluate the adsorption property of activated carbon. The optimal preparation conditions were determined as follows: irradiation time 17 min, impregnation time 240 min, and mass ratio of alkali-to-char 1.5:1. Meanwhile, the relatively high iodine adsorption value (1141.4 mg/g) was also obtained. Furthermore, the pore structural characterization of activated carbon was analyzed. The analyzed results showed a larger Brunauer-Emmett-Teller (BET) specific surface area (1254.5 m(2)/g) and a higher microporosity ratio (87.2%), a bigger total pore volume (0.6565 m(3)/g), but a smaller average pore size (2.093 nm), which demonstrated the obtained activated carbon possessed strong adsorption capacity and well-developed microporous structure. This research could not only establish the foundation of utilizing chestnut burs to prepare activated carbon, but also provide the basis for exploitation of Chinese chestnut by-products. IMPLICATIONS: Because Chinese chestnut burs are the by-products and usually discarded upon harvesting subsequently, the utilization of chestnut burs as a potential source of activated carbon is of great profit to the chestnut processing industries. PMID- 26284757 TI - Spring jumpers vs power jumpers: ankle joint behavior in elite wushu athletes and implications for performance and injury risk. PMID- 26284759 TI - Desaturase Activity Is Associated With Weight Status and Metabolic Risk Markers in Young Children. AB - CONTEXT: Activity of delta-9, delta-6, and delta-5 desaturases (D9D, D6D, D5D) are associated with obesity, insulin resistance, and dyslipidemia. OBJECTIVE: To investigate the association of estimated desaturase activities with weight status, insulin resistance, and dyslipidemia in children, cross-sectionally and longitudinally. DESIGN: The IDEFICS (Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants) cohort study was used, with examinations at baseline (T0) and after 2 years (T1). SETTING AND PARTICIPANTS: Children aged 2 to less than 10 years from eight European countries were recruited in kindergartens/primary schools. Children with available data on fatty acids, outcome, and covariate information were included in the analyses. METHODS: Whole blood fatty acids were analyzed in 2600 children at baseline. D9D (16:1n-7/16:0), D6D (20:3n-6/18:2n-6), and D5D (20:4n-6/20:3n-6) activities were estimated from product-precursor fatty acids ratios. Body mass index (BMI), Homeostatic Model Assessment index, and high-density lipoprotein cholesterol (HDL), and triglycerides (TG) served as outcomes for weight status, insulin resistance, and dyslipidemia, respectively. Linear and logistic regression and repeated measures models were used to assess the cross-sectional and longitudinal associations between desaturase activity and outcomes. RESULTS: In the cross sectional analysis, D9D and D6D were positively associated with BMI and TG z scores and inversely with HDL z-scores. D5D was inversely associated with BMI and TG z-scores (ie, a D5D increase of 1 unit is associated with a BMI z-score decrease of 0.07 and a 28% lower odds ratio for TG >= 75th percentile). Longitudinally, similar associations were found for T0 desaturase activities with BMI and for T0 D6D with HDL at follow-up (T1). Baseline D6D and D5D were positively associated with the change of HDL z-score from T0 to T1, and D6D with the change of Homeostatic Model Assessment index z-score. CONCLUSION: Desaturase activities are associated with metabolic risk markers already in young children and appear to predict the metabolic risk. PMID- 26284758 TI - Insights Into SMAD4 Loss in Pancreatic Cancer From Inducible Restoration of TGF beta Signaling. AB - Pancreatic ductal adenocarcinoma (PDAC) is the fourth-leading cause of cancer death in the United States. The TGF-beta signaling protein SMAD family member 4 is lost in 60% of PDAC, and this has been associated with poorer prognosis. However, the mechanisms by which SMAD4 loss promotes PDAC development are not fully understood. We expressed SMAD4 in human PDAC cell lines BxPC3 and CFPAC1 by selection of stable clones containing an inducible SMAD4 tetracycline inducible expression system construct. After 24 hours of SMAD4 expression, TGF-beta signaling-dependent G1 arrest was observed in BxPC3 cells with an increase in the G1 phase fraction from 48.9% to 71.5%. Inhibition of cyclin-dependent kinase inhibitor 1A by small interfering RNA eliminated the antiproliferative effect, indicating that up-regulation of cyclin-dependent kinase inhibitor 1A/p21 by TGF beta signaling is necessary for the phenotype. SMAD4 expression had no impact on invasion in BxPC3 cells, but reduced migration. Microarray analysis of gene expression at 8, 24, and 48 hours after SMAD4 expression characterized the regulatory impact of SMAD4 expression in a SMAD4-null PDAC cell line and identified novel targets of TGF-beta signaling. Among the novel TGF-beta targets identified are anthrax toxin receptor 2 (3.58* at 8 h), tubulin, beta-3 class III (7.35* at 8 h), cell migration inducing protein, hyaluronan binding (8.07* at 8 h), IL-1 receptor-like 1 (0.403* at 8 h), regulator of G protein signaling 4 (0.293* at 8 h), and THAP domain containing 11 (0.262* at 8 h). The gene expression changes we observed upon restoration of TGF-beta signaling provide numerous new targets for future investigations into PDAC biology and progression. PMID- 26284761 TI - An Incidental Finding of Skull Hemangioma During 18F-FP CIT Brain PET/CT. AB - F-FP CIT has been well established and used for the differential diagnosis of atypical parkinsonian disorders, including idiopathic Parkinson disease. A 54 year-old woman with a history of left hand and leg tremor underwent F-FP CIT PET/CT for the differentiation of parkinsonism. The F-FP CIT PET/CT incidentally showed focal dopamine transporter uptake in the right frontal bone. Brain MRI scan showed heterogeneous high signal intensity with enhancement in right frontal bone diploic space without cortical disruption, suggestive of cavernous hemangioma. Besides the nigrostriatal dopaminergic system, F-FP CIT PET/CT showed a skull tumor. PMID- 26284760 TI - Directed evolution of xylose specific transporters to facilitate glucose-xylose co-utilization. AB - A highly active xylose specific transporter without glucose inhibition is highly desirable in cost-effective production of biofuels from lignocellulosic biomass. However, currently available xylose specific transporters suffer from low overall activity and most are inhibited by glucose. In this study, we applied a directed evolution strategy to engineer the xylose specific transporter AN25 from Neurospora crassa with improved xylose transportation capacity. After four rounds of directed evolution using two different strategies, we obtained an AN25 mutant AN25-R4.18 with 43-fold improvement in terms of xylose transportation capacity while maintaining its high xylose specificity. In addition, glucose inhibition was almost completely eliminated in the final evolved mutant. We demonstrated that improved xylose transportation of AN25 mutants in the exponential growth phase led to significant improvement of xylose consumption in high cell-density fermentation. Finally, we showed that AN25 mutant AN25-R4.18 can enable relatively efficient glucose-xylose co-utilization in high concentrations of mixed sugars. PMID- 26284762 TI - Quantification of Intratumoral Metabolic Macroheterogeneity on 18F-FDG PET/CT and Its Prognostic Significance in Pathologic N0 Squamous Cell Lung Carcinoma. AB - PURPOSE: This study aimed to develop a novel quantification method for intratumoral metabolic macroheterogeneity (IMMH) on F-FDG PET/CT and evaluate its prognostic significance in pathologic N0 (pN0) squamous cell lung carcinoma (SQCLC) patients. PATIENTS AND METHODS: A total of 83 patients who underwent pretreatment F-FDG PET/CT and were diagnosed with pN0 SQCLC after curative surgery were examined. Patients with tumor measuring greater than 2 cm were included. Metabolic parameters (SUVmax, metabolic tumor volume, and total lesion glycolysis) for the primary lesions were calculated on the F-FDG PET/CT, and IMMH was quantified as the macroheterogeneity factor (MHF), defined as surface/spherical surface area having volume of the primary tumor multiplied by the sphericity. Heterogeneity of the primary tumor was also visually assessed (visual heterogeneity score) and compared with MHF. Univariate and multivariate analyses for recurrence were performed using the Cox proportional hazards regression. RESULTS: Recurrence was observed in 27 (32.5%) of 83 patients during follow-up period (37.6 +/- 25.5 months). Significant correlations were observed between the visual heterogeneity score and the MHF (R = 0.534, P < 0.001). Macroheterogeneity factor was significantly higher in patients who experienced recurrence (median, 1.073 vs 1.016; P = 0.004). Univariate analysis showed that MHF was only significant prognostic factor for recurrence (P = 0.019), and multivariate analysis after adjusting for age, sex, tumor size, histologic grade, and pathologic T stage, high MHF exhibited an association with increased risk of recurrence. CONCLUSIONS: New quantification method for IMMH on F-FDG PET/CT was developed, and the heterogeneity parameter MHF was well correlated with visual heterogeneity. Macroheterogeneity factor on pretreatment F-FDG PET/CT was the sole prognostic factor predicting recurrence in pN0 SQCLC patients. PMID- 26284764 TI - Amyloid Imaging With 11C-PIB in Patients With Cognitive Impairment in a Clinical Setting: A Visual and Semiquantitative Analysis. AB - PURPOSE: The aim of this study was to evaluate amyloid imaging with 11C-PIB PET/CT in the study of cognitive impairment in a clinical setting. PATIENTS AND METHODS: The study included 64 patients, with a mean age of 65 years, classified as subjective memory complaints (SMCs; n = 8), nonamnestic mild cognitive impairment (NA-MCI; n = 10), amnestic MCI (A-MCI; n = 19), prodromal Alzheimer disease (AD; n = 12), suspicion of frontotemporal dementia (n = 8), Lewy bodies dementia (DLB; n = 2), and cortical degeneration (CD; n = 5). Ten healthy controls (HCs), with a mean age of 59 years, were also included. 11C-PIB was acquired 60 minutes after IV injection of 555 MBq 11C-PIB. A visual and semiquantitative analysis was performed. RESULTS: In HC, 11C-PIB was negative in 9 and positive in 1. Of the 64 patients, 11C-PIB was negative in 27 (42%) and positive in 37 (58%). 11C-PIB was positive in 3 of 8 SMC, in none of 10 NA-MCI, in 14 of 19 A-MCI, in 10 of 12 prodromal AD, in 3 of 8 frontotemporal dementia, and in the 2 and 5 DLB and CD patients. The semiquantitative results in terms of mean global SUV ratio were 1.13 for HC, 1.36 for SMC, 1.07 for NA-MCI, 2.01 for A MCI, 2.37 for prodromal AD, 2.75 for DLB, and 2.44 for CD. CONCLUSIONS: In a clinical setting, 11C-PIB scan had a relevant contribution on patients with cognitive impairment, excluding AD in a high proportion of MCI patients and differentiating AD from other dementias. In A-MCI, 11C-PIB revealed beta-amyloid deposit in 74%, whereas it was negative in all NA-MCI patients. PMID- 26284763 TI - Peptide Receptor Radionuclide Therapy-Induced Hepatotoxicity in Patients With Metastatic Neuroendocrine Tumors. AB - BACKGROUND: Treatment of metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) with peptide receptor radionuclide therapy (PRRT) is effective in retarding tumor growth. Renal dysfunction, anemia, and thrombocytopenia are well described treatment-related toxicities. However, hepatotoxicity is not well recognized. PATIENTS AND METHODS: We performed a retrospective cohort study of consecutive patients with GEP-NETs seen in a tertiary NET clinic from January 2010 to September 2013 (n = 211) with the primary study cohort being patients with metastatic disease to the liver (n = 93). The study exposure was PRRT, and the primary outcome of interest was hepatotoxicity. Hepatotoxicity was defined as a grade 2 or greater injury according to the Common Terminology Criteria for Adverse Events version 3.0 of the National Cancer Institute. RESULTS: Seventeen (18%) of 93 patients with liver metastases received PRRT after radiographic confirmation of disease progression despite receipt of other traditional therapies. Peptide receptor radionuclide therapy patients were similar to the unexposed patient population in terms of sex, age, baseline laboratory values, prior treatment exposure, and duration of disease. In the unexposed group, 23 (30%) of 76 patients had hepatotoxicity related to traditional GEP-NET therapy. In the exposed group, 10 (59%) of 17 patients had an episode of hepatotoxicity. Ascites developed in 59% of the PRRT group versus 6.6% in the unexposed group (P < 0.001). The calculated relative risk of hepatotoxicity related to PRRT exposure in metastatic GEP-NET patients was 1.94 (95% confidence interval, 1.15-3.28). CONCLUSIONS: Hepatotoxicity after PRRT for metastatic GEP-NET is more common than previously reported. PMID- 26284765 TI - Pancreatitis Secondary to Anti-Programmed Death Receptor 1 Immunotherapy Diagnosed by FDG PET/CT. AB - A 57-year-old man with metastatic melanoma developed colitis secondary to ipilimumab, a known immune-related adverse event (irAE). The patient then received pembrolizumab immunotherapy, an anti-programmed-death-receptor-1 (PD-1) antibody. Restaging FDG PET/CT study following 3 cycles of therapy demonstrated diffuse increased FDG uptake throughout the body of the pancreas associated with fat stranding in the peripancreatic region, suggestive of pembrolizumab-induced pancreatitis. Although the patient was clinically asymptomatic, diagnosis was biochemically confirmed with elevated amylase and lipase levels. In the era of immunotherapy, it will be critical to recognize irAEs early to allow prompt initiation of appropriate therapy and reduce the risk of long-term sequelae. PMID- 26284766 TI - FDG PET/CT Imaging of an Isolated Recurrence in the Eyelid of a Patient With Follicular Lymphoma. AB - An 80-year-old woman had a history of follicular lymphoma diagnosed by biopsy of the inguinal lymph node 4 years prior. After systemic chemotherapy, she achieved complete remission. She presented with painless swelling on the left side of the eyelid. She also had suspicious lymph node enlargement in the cervical and axillary regions. FDG PET/CT showed an isolated FDG-avid lesion on the eyelid that was confirmed by biopsy to be compatible with lymphoma recurrence. PMID- 26284767 TI - FDG PET/CT in Monitoring Antituberculosis Therapy in Patient With Widespread Skeletal Tuberculosis. AB - FDG PET/CT imaging is a useful diagnostic tool in the evaluation of both neoplastic and inflammatory lesions and has a promising role in monitoring therapeutic response. We present a 50-year-old man whose initial PET/CT scan showed multiple foci of intense FDG activity in lytic lesions in the bones. A diagnosis of skeletal tuberculosis was confirmed after bone biopsy. Follow-up FDG PET/CT performed after 12 months of regular antituberculosis treatment demonstrated complete normalization of FDG activity in the bones. PMID- 26284768 TI - 18F-Florbetapir and 18F-FDG PET/CT in Systemic Immunoglobulin Light Chain Amyloidosis Involving the Peripheral Nerves. AB - We present a case of both F-FDG and F-florbetapir uptake in a biopsy-confirmed immunoglobulin light chain (AL) amyloidosis involving the peripheral nerves. AL amyloidosis is the most common cause of acquired amyloid polyneuropathy, manifesting with both sensorimotor and autonomic neuronal dysfunction. Given the overlapping MRI and FDG PET/CT appearances of several different causes of peripheral neuropathy, F-florbetapir PET/CT provides another potential tool in the imaging algorithm of these patients and may guide targeted fascicular biopsy for pathologic confirmation. PMID- 26284769 TI - Long-lasting FDG uptake in the muscles after strenuous exercise. AB - FDG PET/CT imaging guidelines require avoiding exercise 24 hours before FDG administration. We report here a case of intense skeletal muscle FDG activity in a 15-year-old adolescent boy who had vigorous exercise 4 days before undertaking FDG PET/CT scan. PMID- 26284770 TI - Imaging Idiopathic Chylopericardium With 99mTc-SC Lymphoscintigraphy and SPECT/CT. AB - A 27-year-old asymptomatic active duty military man underwent a screening chest x ray secondary to a history of tuberculosis exposure. His chest x-ray showed no features of tuberculosis infection but unexpectedly revealed a markedly enlarged cardiac silhouette. Echocardiography demonstrated a large pericardial effusion without tamponade physiology. Pericardiocentesis revealed chylous fluid. The effusion was initially refractory to drainage requiring VATS for therapy. Lymphoscintigraphy was performed using Tc-SC to evaluate lymphatic anatomy and confirm communication with the pericardial space. Novel use was made of SPECT/CT with the hope of better assessing the nature of the abnormal communication and potentially helping guide management. PMID- 26284771 TI - Prior CT May Improve Diagnostic Confidence in Myocardial Perfusion Imaging. AB - PURPOSE: Many patients with matching myocardial perfusion imaging defects may have prior CT examinations that include the myocardial region of interest, such as a CT chest or CT abdomen. We correlate these perfusion defects with available prior CT examinations to determine if this will improve diagnostic confidence. METHODS: Myocardial perfusion scans were reviewed to identify cases with myocardial perfusion defects and prior CT imaging that included the myocardium. The CT was reviewed for evidence of myocardial injury that correlated with the perfusion defect. RESULTS: A retrospective review of 732 myocardial perfusion scans was performed, of which 69 cases with perfusion defects were identified that also had prior CT imaging available for review. Of this subset of patients, 19 patients had findings on the CT scan compatible with ischemia or infarction in the expected region of the perfusion defect, which allowed for a more confident diagnosis. CONCLUSIONS: Reviewing a prior CT scan, if available, during the interpretation of a myocardial perfusion scan, can help improve diagnostic confidence in over 25% of cases. This can lead to decreased indeterminate results and can be used to potentially avoid unhelpful further testing. PMID- 26284772 TI - Renographic Demonstration of Desmoid Tumor-Ureteral Fistula. AB - A 20-year-old woman with Gardner syndrome and intra-abdominal desmoid tumors presented with increasing abdominal pain. CT demonstrated a new area of central hypodensity in a presumed desmoid tumor, compressing the left ureter. Findings were suspicious for abscess or fistula to the ureter. Subsequent 99mTc-MAG3 renogram demonstrated persistent extraureteral radiotracer activity in the region of the tumor, confirming a desmoid tumor-ureteral fistula. Desmoid tumors are benign but locally aggressive fibrous neoplasms that can be sporadic or associated with familial adenomatous polyposis syndromes, specifically Gardner syndrome. Fistula formation to the ureter has been reported infrequently. PMID- 26284773 TI - Initial Experience of 18F-FDG PET/MRI in Thymic Epithelial Tumors: Morphologic, Functional, and Metabolic Biomarkers. AB - PURPOSE: The aim of this study was to investigate the value of morphologic, functional, and metabolic biomarkers acquired concurrently at PET/MRI in patients with thymic epithelial tumors. PATIENTS AND METHODS: During 1 year, 9 patients with suspected thymic epithelial tumors at contrast-enhanced chest CT were prospectively enrolled and underwent preoperative 18F-FDG PET/MRI. Two chest radiologists prospectively reviewed the CT and MRI scans of PET/MRI in consensus, and 2 nuclear physicians reviewed the PET images. Visual assessment of the tumor morphology, functional biomarkers such as apparent diffusion coefficient from diffusion-weighted images, and metabolic biomarkers (including SUVmax, metabolic tumor volume, total lesion glycolysis, and heterogeneity index) were recorded. All patients underwent operation, and their pathologic reports served as the reference standard. RESULTS: Thymic epithelial tumors were demonstrated in all 9 patients at pathologic examination. Tumor contour (P = 0.012) and shape (P = 0.033) had an association with the World Health Organization subtype, and the presence of septum (P = 0.048) on MRI scans had an association with the Masaoka stage. In terms of functional and metabolic biomarkers, SUVmax (rho = 0.683, P = 0.042) and SUV/apparent diffusion coefficient (rho = 0.703, P = 0.035) correlated with the Masaoka stage. Metabolic tumor volume (P = 0.024), heterogeneity index (P = 0.024), and total lesion glycolysis (P = 0.048) were useful for classification between low- and high-risk thymic epithelial tumors. CONCLUSIONS: Although limited by the small number of patients enrolled, morphologic, functional, and metabolic biomarkers derived from PET/MRI scans were useful for the stratification of thymic epithelial tumors. PMID- 26284774 TI - Secondary Hyperparathyroidism With "Superscan-Like" Hypermetabolic FDG PET/CT Pattern. AB - A 26-year-old man with chronic terminal renal insufficiency under dialysis was referred in our institution for a checkup before kidney transplantation to ensure the absence of malignant neoplasm. The patient had a biological secondary hyperparathyroidism with highly elevated serum parathormon, and treatment with parathyroid surgery was planned before the kidney transplant. Whole-body FDG PET/CT showed no apparent malignant neoplasm, but increased metabolism of the 4 parathyroid gland and the other pitfalls of advanced secondary hyperparathyroidism on chronic renal insufficiency: pseudotumoral calcification in soft tissues, diffuse hypermetabolic bone dystrophy, and osteolytic lesion of pelvic and peripheral skeleton corresponding to brown tumors. PMID- 26284775 TI - Adenocarcinoma of the Cervix Uteri and Endometrium Combined With the Kartagener Syndrome on FDG PET/CT. AB - A 45-year-old woman with pathologically confirmed adenocarcinoma of the cervix uteri and endometrium underwent FDG PET/CT for staging. No metastasis was found. However, the images revealed bronchiectasis, sinusitis, and situs inversus totalis, which are the triad of Kartagener syndrome. PMID- 26284776 TI - Localization of Parathyroid Adenoma With Real-Time Ultrasound: Freehand SPECT Fusion. AB - Preoperative localization of parathyroid adenoma in primary hyperparathyroidism gains in importance as there is a trend toward minimally invasive parathyroid surgery. Besides MRI, 4-dimensional CT, PET/CT, invasive-selective venous sampling, or angiography, both ultrasound and scintigraphy are standard of care for lesion localization. Here we report on a 53-year-old woman with suspicion of primary hyperparathyroidism using real-time fusion of scintigraphic (freehand SPECT) and ultrasound imaging for adenoma localization. Real-time fusion of ultrasound and freehand SPECT allowed noninvasive dedicated metabolic and anatomic adenoma localization and treatment planning. PMID- 26284778 TI - A Novel Multiparametric Approach to 3D Quantitative MRI of the Brain. AB - Magnetic Resonance properties of tissues can be quantified in several respects: relaxation processes, density of imaged nuclei, magnetism of environmental molecules, etc. In this paper, we propose a new comprehensive approach to obtain 3D high resolution quantitative maps of arbitrary body districts, mainly focusing on the brain. The theory presented makes it possible to map longitudinal (R1), pure transverse (R2) and free induction decay ([Formula: see text]) rates, along with proton density (PD) and magnetic susceptibility (chi), from a set of fast acquisition sequences in steady-state that are highly insensitive to flow phenomena. A novel denoising scheme is described and applied to the acquired datasets to enhance the signal to noise ratio of the derived maps and an information theory approach compensates for biases from radio frequency (RF) inhomogeneities, if no direct measure of the RF field is available. Finally, the results obtained on sample brain scans of healthy controls and multiple sclerosis patients are presented and discussed. PMID- 26284779 TI - Does Angling Technique Selectively Target Fishes Based on Their Behavioural Type? AB - Recently, there has been growing recognition that fish harvesting practices can have important impacts on the phenotypic distributions and diversity of natural populations through a phenomenon known as fisheries-induced evolution. Here we experimentally show that two common recreational angling techniques (active crank baits versus passive soft plastics) differentially target wild largemouth bass (Micropterus salmoides) and rock bass (Ambloplites rupestris) based on variation in their behavioural tendencies. Fish were first angled in the wild using both techniques and then brought back to the laboratory and tested for individual level differences in common estimates of personality (refuge emergence, flight initiation-distance, latency-to-recapture and with a net, and general activity) in an in-lake experimental arena. We found that different angling techniques appear to selectively target these species based on their boldness (as characterized by refuge emergence, a standard measure of boldness in fishes) but not other assays of personality. We also observed that body size was independently a significant predictor of personality in both species, though this varied between traits and species. Our results suggest a context-dependency for vulnerability to capture relative to behaviour in these fish species. Ascertaining the selective pressures angling practices exert on natural populations is an important area of fisheries research with significant implications for ecology, evolution, and resource management. PMID- 26284780 TI - Comparison of Toxoplasma gondii Seroprevalence in Shelter Cats and Dogs during 1999-2001 and 2009-2011 in Tokyo, Japan. AB - Toxoplasma gondii is an important human health concern with respect to abortion, congenital hydrocephalus, and encephalitis in immunocompromised people. Cats and dogs both are potential sources of T. gondii because they have close contact with humans. However, no epidemiological surveys have been conducted in Tokyo over the past decade. Therefore, the present study investigated and compared the seroprevalence of T. gondii infection in shelter cats and dogs during 1999-2001 and 2009-2011 in Tokyo, Japan. Serum samples were collected from 337 shelter cats and 325 shelter dogs in urban and suburban areas of Tokyo, during 1999-2001 (233 cats and 219 dogs) and 2009-2011 (104 cats and 106 dogs). T. gondii antibodies were measured in the serum samples using a commercial latex agglutination test. Data were compared using the Fisher's exact test, and significance was indicated at P < 0.05. The overall seroprevalence of T. gondii infection in cats was 5.6% (13 of 233) in 1999-2001 and 6.7% (7 of 104) in 2009-2011, and that in dogs was 1.8% (4 of 219) and 1.9% (2 of 106), respectively. Significantly higher seroprevalence was observed in cats from suburban areas compared with cats in urban areas during both periods (P < 0.05). These results reveal that there has been little change in the feline and canine seroprevalence over the past decade, indicating that the risk of T. gondii exposure for cats and dogs in Tokyo is considerably low as the seroprevalence has reached a steady state. PMID- 26284777 TI - Host Biology in Light of the Microbiome: Ten Principles of Holobionts and Hologenomes. AB - Groundbreaking research on the universality and diversity of microorganisms is now challenging the life sciences to upgrade fundamental theories that once seemed untouchable. To fully appreciate the change that the field is now undergoing, one has to place the epochs and foundational principles of Darwin, Mendel, and the modern synthesis in light of the current advances that are enabling a new vision for the central importance of microbiology. Animals and plants are no longer heralded as autonomous entities but rather as biomolecular networks composed of the host plus its associated microbes, i.e., "holobionts." As such, their collective genomes forge a "hologenome," and models of animal and plant biology that do not account for these intergenomic associations are incomplete. Here, we integrate these concepts into historical and contemporary visions of biology and summarize a predictive and refutable framework for their evaluation. Specifically, we present ten principles that clarify and append what these concepts are and are not, explain how they both support and extend existing theory in the life sciences, and discuss their potential ramifications for the multifaceted approaches of zoology and botany. We anticipate that the conceptual and evidence-based foundation provided in this essay will serve as a roadmap for hypothesis-driven, experimentally validated research on holobionts and their hologenomes, thereby catalyzing the continued fusion of biology's subdisciplines. At a time when symbiotic microbes are recognized as fundamental to all aspects of animal and plant biology, the holobiont and hologenome concepts afford a holistic view of biological complexity that is consistent with the generally reductionist approaches of biology. PMID- 26284781 TI - Conformational Polymorphism in Autophagy-Related Protein GATE-16. AB - Autophagy is a fundamental homeostatic process in eukaryotic organisms, fulfilling essential roles in development and adaptation to stress. Among other factors, formation of autophagosomes critically depends on proteins of the Atg8 (autophagy-related protein 8) family, which are reversibly conjugated to membrane lipids. We have applied X-ray crystallography, nuclear magnetic resonance spectroscopy, and molecular dynamics simulations to study the conformational dynamics of Atg8-type proteins, using GATE-16 (Golgi-associated ATPase enhancer of 16 kDa), also known as GABARAPL2, as a model system. This combination of complementary approaches provides new insight into a structural transition centered on the C-terminus, which is crucial for the biological activity of these proteins. PMID- 26284783 TI - A wafer-scale graphene and ferroelectric multilayer for flexible and fast switched modulation applications. AB - Here we report a wafer-scale graphene/P(VDF-TrFE)/graphene multilayer for light weight, flexible and fast-switched broadband modulation applications. The P(VDF TrFE) film not only significantly reduces the sheet resistance of graphene throughout heavy doping of ~0.8 * 10(13) cm(-2) by nonvolatile ferroelectric dipoles, but also acts as an efficient electro-optic (EO) layer. Such multilayered structural integration with remarkable ferroelectric polarization, high transparency (>90%), low sheet resistance (~302 Omega?(-1)), and excellent mechanic flexibility shows the potential of a flexible modulation application over a broad range of wavelengths. Moreover, the derived device also exhibits strong field-induced EO modulation even under bending and one large Pockels coefficient (~54.3 pm V(-1)) is obtained. Finally, the graphene and ferroelectric hybrid demonstrates a fast switching time (~2 MUs) and works well below low sheet resistance level over a long time. This work gives insights into the potential of graphene and ferroelectric hybrid structures, enabling future exploration on next generation high-performance, flexible transparent electronics and photonics. PMID- 26284782 TI - Association Mapping for Fruit, Plant and Leaf Morphology Traits in Eggplant. AB - An eggplant (Solanum melongena) association panel of 191 accessions, comprising a mixture of breeding lines, old varieties and landrace selections was SNP genotyped and phenotyped for key breeding fruit and plant traits at two locations over two seasons. A genome-wide association (GWA) analysis was performed using the mixed linear model, which takes into account both a kinship matrix and the sub-population membership of the accessions. Overall, 194 phenotype/genotype associations were uncovered, relating to 30 of the 33 measured traits. These associations involved 79 SNP loci mapping to 39 distinct chromosomal regions distributed over all 12 eggplant chromosomes. A comparison of the map positions of these SNPs with those of loci derived from conventional linkage mapping showed that GWA analysis both validated many of the known controlling loci and detected a large number of new marker/trait associations. Exploiting established syntenic relationships between eggplant chromosomes and those of tomato and pepper recognized orthologous regions in ten eggplant chromosomes harbouring genes influencing breeders' traits. PMID- 26284785 TI - Dynamic Monitoring Reveals Motor Task Characteristics in Prehistoric Technical Gestures. AB - Reconstructing ancient technical gestures associated with simple tool actions is crucial for understanding the co-evolution of the human forelimb and its associated control-related cognitive functions on the one hand, and of the human technological arsenal on the other hand. Although the topic of gesture is an old one in Paleolithic archaeology and in anthropology in general, very few studies have taken advantage of the new technologies from the science of kinematics in order to improve replicative experimental protocols. Recent work in paleoanthropology has shown the potential of monitored replicative experiments to reconstruct tool-use-related motions through the study of fossil bones, but so far comparatively little has been done to examine the dynamics of the tool itself. In this paper, we demonstrate that we can statistically differentiate gestures used in a simple scraping task through dynamic monitoring. Dynamics combines kinematics (position, orientation, and speed) with contact mechanical parameters (force and torque). Taken together, these parameters are important because they play a role in the formation of a visible archaeological signature, use-wear. We present our new affordable, yet precise methodology for measuring the dynamics of a simple hide-scraping task, carried out using a pull-to (PT) and a push-away (PA) gesture. A strain gage force sensor combined with a visual tag tracking system records force, torque, as well as position and orientation of hafted flint stone tools. The set-up allows switching between two tool configurations, one with distal and the other one with perpendicular hafting of the scrapers, to allow for ethnographically plausible reconstructions. The data show statistically significant differences between the two gestures: scraping away from the body (PA) generates higher shearing forces, but requires greater hand torque. Moreover, most benchmarks associated with the PA gesture are more highly variable than in the PT gesture. These results demonstrate that different gestures used in 'common' prehistoric tasks can be distinguished quantitatively based on their dynamic parameters. Future research needs to assess our ability to reconstruct these parameters from observed use-wear patterns. PMID- 26284784 TI - Screening of Non- Saccharomyces cerevisiae Strains for Tolerance to Formic Acid in Bioethanol Fermentation. AB - Formic acid is one of the major inhibitory compounds present in hydrolysates derived from lignocellulosic materials, the presence of which can significantly hamper the efficiency of converting available sugars into bioethanol. This study investigated the potential for screening formic acid tolerance in non Saccharomyces cerevisiae yeast strains, which could be used for the development of advanced generation bioethanol processes. Spot plate and phenotypic microarray methods were used to screen the formic acid tolerance of 7 non-Saccharomyces cerevisiae yeasts. S. kudriavzeii IFO1802 and S. arboricolus 2.3319 displayed a higher formic acid tolerance when compared to other strains in the study. Strain S. arboricolus 2.3319 was selected for further investigation due to its genetic variability among the Saccharomyces species as related to Saccharomyces cerevisiae and availability of two sibling strains: S. arboricolus 2.3317 and 2.3318 in the lab. The tolerance of S. arboricolus strains (2.3317, 2.3318 and 2.3319) to formic acid was further investigated by lab-scale fermentation analysis, and compared with S. cerevisiae NCYC2592. S. arboricolus 2.3319 demonstrated improved formic acid tolerance and a similar bioethanol synthesis capacity to S. cerevisiae NCYC2592, while S. arboricolus 2.3317 and 2.3318 exhibited an overall inferior performance. Metabolite analysis indicated that S. arboricolus strain 2.3319 accumulated comparatively high concentrations of glycerol and glycogen, which may have contributed to its ability to tolerate high levels of formic acid. PMID- 26284786 TI - Dynamic Metabolite Profiling in an Archaeon Connects Transcriptional Regulation to Metabolic Consequences. AB - Previous work demonstrated that the TrmB transcription factor is responsible for regulating the expression of many enzyme-coding genes in the hypersaline-adapted archaeon Halobacterium salinarum via a direct interaction with a cis-regulatory sequence in their promoters. This interaction is abolished in the presence of glucose. Although much is known about the effects of TrmB at the transcriptional level, it remains unclear whether and to what extent changes in mRNA levels directly affect metabolite levels. In order to address this question, here we performed a high-resolution metabolite profiling time course during a change in nutrients using a combination of targeted and untargeted methods in wild-type and DeltatrmB strain backgrounds. We found that TrmB-mediated transcriptional changes resulted in widespread and significant changes to metabolite levels across the metabolic network. Additionally, the pattern of growth complementation using various purines suggests that the mis-regulation of gluconeogenesis in the DeltatrmB mutant strain in the absence of glucose results in low phosphoribosylpyrophosphate (PRPP) levels. We confirmed these low PRPP levels using a quantitative mass spectrometric technique and found that they are associated with a metabolic block in de novo purine synthesis, which is partially responsible for the growth defect of the DeltatrmB mutant strain in the absence of glucose. In conclusion, we show how transcriptional regulation of metabolism affects metabolite levels and ultimately, phenotypes. PMID- 26284787 TI - Derivation of an Analytical Solution to a Reaction-Diffusion Model for Autocatalytic Degradation and Erosion in Polymer Microspheres. AB - A mathematical reaction-diffusion model is defined to describe the gradual decomposition of polymer microspheres composed of poly(D,L-lactic-co-glycolic acid) (PLGA) that are used for pharmaceutical drug delivery over extended periods of time. The partial differential equation (PDE) model treats simultaneous first order generation due to chemical reaction and diffusion of reaction products in spherical geometry to capture the microsphere-size-dependent effects of autocatalysis on PLGA erosion that occurs when the microspheres are exposed to aqueous media such as biological fluids. The model is solved analytically for the concentration of the autocatalytic carboxylic acid end groups of the polymer chains that comprise the microspheres as a function of radial position and time. The analytical solution for the reaction and transport of the autocatalytic chemical species is useful for predicting the conditions under which drug release from PLGA microspheres transitions from diffusion-controlled to erosion controlled release, for understanding the dynamic coupling between the PLGA degradation and erosion mechanisms, and for designing drug release particles. The model is the first to provide an analytical prediction for the dynamics and spatial heterogeneities of PLGA degradation and erosion within a spherical particle. The analytical solution is applicable to other spherical systems with simultaneous diffusive transport and first-order generation by reaction. PMID- 26284789 TI - Re-examining the Chevrel phase Mo6S8 cathode for Mg intercalation from an electronic structure perspective. AB - We re-examine the electronic response of the Chevrel phase Mo6S8 upon Mg intercalation. The ground state Mo6S8 is metallic and exhibits strongly localized electronic screening of Mg(2+) ions. This localized screening cloud effectively shields the 2+ charge carried by Mg ions on the length scale of one unit cell and facilitates Mg ion diffusion. PMID- 26284788 TI - Diet- and Genetically-Induced Obesity Differentially Affect the Fecal Microbiome and Metabolome in Apc1638N Mice. AB - Obesity is a risk factor for colorectal cancer (CRC), and alterations in the colonic microbiome and metabolome may be mechanistically involved in this relationship. The relative contribution of diet and obesity per se are unclear. We compared the effect of diet- and genetically-induced obesity on the intestinal microbiome and metabolome in a mouse model of CRC. Apc1638N mice were made obese by either high fat (HF) feeding or the presence of the Leprdb/db (DbDb) mutation. Intestinal tumors were quantified and stool microbiome and metabolome were profiled. Genetic obesity, and to a lesser extent HF feeding, promoted intestinal tumorigenesis. Each induced distinct microbial patterns: taxa enriched in HF were mostly Firmicutes (6 of 8) while those enriched in DbDb were split between Firmicutes (7 of 12) and Proteobacteria (5 of 12). Parabecteroides distasonis was lower in tumor-bearing mice and its abundance was inversely associated with colonic Il1b production (p<0.05). HF and genetic obesity altered the abundance of 49 and 40 fecal metabolites respectively, with 5 in common. Of these 5, adenosine was also lower in obese and in tumor-bearing mice (p<0.05) and its concentration was inversely associated with colonic Il1b and Tnf production (p<0.05). HF and genetic obesity differentially alter the intestinal microbiome and metabolome. A depletion of adenosine and P.distasonis in tumor-bearing mice could play a mechanistic role in tumor formation. Adenosine and P. distasonis have previously been shown to be anti-inflammatory in the colon and we postulate their reduction could promote tumorigenesis by de-repressing inflammation. PMID- 26284790 TI - Assessing the Causal Relationship of Maternal Height on Birth Size and Gestational Age at Birth: A Mendelian Randomization Analysis. AB - BACKGROUND: Observational epidemiological studies indicate that maternal height is associated with gestational age at birth and fetal growth measures (i.e., shorter mothers deliver infants at earlier gestational ages with lower birth weight and birth length). Different mechanisms have been postulated to explain these associations. This study aimed to investigate the casual relationships behind the strong association of maternal height with fetal growth measures (i.e., birth length and birth weight) and gestational age by a Mendelian randomization approach. METHODS AND FINDINGS: We conducted a Mendelian randomization analysis using phenotype and genome-wide single nucleotide polymorphism (SNP) data of 3,485 mother/infant pairs from birth cohorts collected from three Nordic countries (Finland, Denmark, and Norway). We constructed a genetic score based on 697 SNPs known to be associated with adult height to index maternal height. To avoid confounding due to genetic sharing between mother and infant, we inferred parental transmission of the height-associated SNPs and utilized the haplotype genetic score derived from nontransmitted alleles as a valid genetic instrument for maternal height. In observational analysis, maternal height was significantly associated with birth length (p = 6.31 * 10-9), birth weight (p = 2.19 * 10-15), and gestational age (p = 1.51 * 10-7). Our parental specific haplotype score association analysis revealed that birth length and birth weight were significantly associated with the maternal transmitted haplotype score as well as the paternal transmitted haplotype score. Their association with the maternal nontransmitted haplotype score was far less significant, indicating a major fetal genetic influence on these fetal growth measures. In contrast, gestational age was significantly associated with the nontransmitted haplotype score (p = 0.0424) and demonstrated a significant (p = 0.0234) causal effect of every 1 cm increase in maternal height resulting in ~0.4 more gestational d. Limitations of this study include potential influences in causal inference by biological pleiotropy, assortative mating, and the nonrandom sampling of study subjects. CONCLUSIONS: Our results demonstrate that the observed association between maternal height and fetal growth measures (i.e., birth length and birth weight) is mainly defined by fetal genetics. In contrast, the association between maternal height and gestational age is more likely to be causal. In addition, our approach that utilizes the genetic score derived from the nontransmitted maternal haplotype as a genetic instrument is a novel extension to the Mendelian randomization methodology in casual inference between parental phenotype (or exposure) and outcomes in offspring. PMID- 26284791 TI - CRISPR/Cas9-Mediated Genome Editing in Soybean Hairy Roots. AB - As a new technology for gene editing, the CRISPR (clustered regularly interspaced short palindromic repeat)/Cas (CRISPR-associated) system has been rapidly and widely used for genome engineering in various organisms. In the present study, we successfully applied type II CRISPR/Cas9 system to generate and estimate genome editing in the desired target genes in soybean (Glycine max (L.) Merrill.). The single-guide RNA (sgRNA) and Cas9 cassettes were assembled on one vector to improve transformation efficiency, and we designed a sgRNA that targeted a transgene (bar) and six sgRNAs that targeted different sites of two endogenous soybean genes (GmFEI2 and GmSHR). The targeted DNA mutations were detected in soybean hairy roots. The results demonstrated that this customized CRISPR/Cas9 system shared the same efficiency for both endogenous and exogenous genes in soybean hairy roots. We also performed experiments to detect the potential of CRISPR/Cas9 system to simultaneously edit two endogenous soybean genes using only one customized sgRNA. Overall, generating and detecting the CRISPR/Cas9-mediated genome modifications in target genes of soybean hairy roots could rapidly assess the efficiency of each target loci. The target sites with higher efficiencies can be used for regular soybean transformation. Furthermore, this method provides a powerful tool for root-specific functional genomics studies in soybean. PMID- 26284793 TI - Elimination of Reperfusion-Induced Microcirculatory Alterations In Vivo by Adipose-Derived Stem Cell Supernatant without Adipose-Derived Stem Cells. PMID- 26284792 TI - Flow Cytofluorimetric Analysis of Anti-LRP4 (LDL Receptor-Related Protein 4) Autoantibodies in Italian Patients with Myasthenia Gravis. AB - BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease in which 90% of patients have autoantibodies against the muscle nicotinic acetylcholine receptor (AChR), while autoantibodies to muscle-specific tyrosine kinase (MuSK) have been detected in half (5%) of the remaining 10%. Recently, the low-density lipoprotein receptor-related protein 4 (LRP4), identified as the agrin receptor, has been recognized as a third autoimmune target in a significant portion of the double sero-negative (dSN) myasthenic individuals, with variable frequency depending on different methods and origin countries of the tested population. There is also convincing experimental evidence that anti-LRP4 autoantibodies may cause MG. METHODS: The aim of this study was to test the presence and diagnostic significance of anti-LRP4 autoantibodies in an Italian population of 101 myasthenic patients (55 dSN, 23 AChR positive and 23 MuSK positive), 45 healthy blood donors and 40 patients with other neurological diseases as controls. All sera were analyzed by a cell-based antigen assay employing LRP4-transfected HEK293T cells, along with a flow cytofluorimetric detection system. RESULTS: We found a 14.5% (8/55) frequency of positivity in the dSN-MG group and a 13% frequency of co-occurrence (3/23) in both AChR and MuSK positive patients; moreover, we report a younger female prevalence with a mild form of disease in LRP4-positive dSN-MG individuals. CONCLUSION: Our data confirm LRP4 as a new autoimmune target, supporting the value of including anti-LRP4 antibodies in further studies on Myasthenia gravis. PMID- 26284794 TI - Reply: Midface Rejuvenation: A Critical Evaluation of a 7-Year Experience. PMID- 26284796 TI - Vaginal Labiaplasty: Current Practices and a Simplified Classification System for Labial Protrusion. PMID- 26284797 TI - Reply: Vaginal Labiaplasty: Current Practices and a Simplified Classification System for Labial Protrusion. PMID- 26284798 TI - Cadaveric Study of Breast Measurements during Augmentation with Implants. PMID- 26284799 TI - Spatial/Frontal QRS-T Angle Predicts All-Cause Mortality and Cardiac Mortality: A Meta-Analysis. AB - BACKGROUND: A number of studies have assessed the predictive effect of QRS-T angles in various populations since the last decade. The objective of this meta analysis was to evaluate the prognostic value of spatial/frontal QRS-T angle on all-cause death and cardiac death. METHODS: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from their inception until June 5, 2014. Studies reporting the predictive effect of spatial/frontal QRS-T angle on all-cause/cardiac death in all populations were included. Relative risk (RR) was used as a measure of effect. RESULTS: Twenty-two studies enrolling 164,171 individuals were included. In the combined analysis in all populations, a wide spatial QRS-T angle was associated with an increase in all-cause death (maximum-adjusted RR: 1.40; 95% confidence interval [CI]: 1.32 to 1.48) and cardiac death (maximum-adjusted RR: 1.71; 95% CI: 1.54 to 1.90), a wide frontal QRS-T angle also predicted a higher rate of all-cause death (maximum-adjusted RR: 1.71; 95% CI: 1.54 to 1.90). Largely similar results were found using different methods of categorizing for QRS-T angles, and similar in subgroup populations such as general population, populations with suspected coronary heart disease or heart failure. Other stratified analyses and meta-analyses using unadjusted data also generated consistent findings. CONCLUSIONS: Spatial QRS-T angle held promising prognostic value on all-cause death and cardiac death. Frontal QRS-T angle was also a promising predictor of all-cause death. Given the good predictive value of QRS-T angle, a combined stratification strategy in which QRS T angle is of vital importance might be expected. PMID- 26284800 TI - [In Process Citation]. AB - The blunt injury of the thoracic aorta constitutes one of the most severe chapter of traumatology. Open and transmural aortic injury leads to death on site, but its blunt trauma provides chance for survival if expeditious transport, diagnostic workup and proper selection of treatment are given. The blunt trauma of the aorta usually is a part of multiple injuries which determines the final outcome significantly. To select among acute, subacute interventions and conservative treatment options needs great experience following personalized algorithm. The wide variety of the clinical picture makes difficult to formulate an individualized clear guideline - so we think it is important to summarise own experiences and overview related literature. PMID- 26284801 TI - [In Process Citation]. AB - INTRODUCTION: The adequate exposure of the upper abdominal aorta and its side branches are essential for vascular reconstruction of this region. Besides the traditional transperitoneal, retroperitoneal approach or thoracolaparotomy, left medial visceral rotation (MVR) is an option to explore this hardly accessible region. We present our MVR experiences in aortic surgery. METHODS: Using median or subcostal laparotomy we mobilised the left colon, the spleen, the pancreas and performed dissection in the retroperitoneal area leaving the left kidney in place. The indications of surgery were suprarenal aneurysm in one case, extensively calcified aortic atherosclerosis causing significant stenosis in three cases, postoperative anastomotic pseudoaneurysm in one case and type B aortic dissection causing malperfusion in one case. We performed two thrombendarterectomies (TEA), one TEA with aortobifemoral bypass grafting, two aortic interposition with dacron prosthesis and cryopreserved homograft and one aortic refenestration. RESULTS: the median age was 58 years (43-72). The average operation time was 231 +/- 80 minutes, average supraceliac crossclamping time was 43 +/- 15 minutes. We used cell saver in three cases. Average hospital stay was 16.16 +/- 13.53 days. One patient suffered spleen capsule injury requiring splenectomy and 2 patients had reoperation because of bleeding. Two patients developed renal failure, one of them required long-term dialysis. No death, pancreatitis or bowel necrosis occurred. CONCLUSIONS: Based on trauma experience, transabdominal medial visceral rotation provides a good exposure for acute or elective vascular reconstruction of the upper abdominal aortic segment. The intraoperative bleeding control, the approach of the distal part of visceral arteries is more accessible using laparotomy and lateral aortic exploration. The thoracolaparotomy with opening of two body cavities causes higher morbidity, mainly pulmonary complications. Further advantage of MVR is the direct access of abdominal organs and its vessels. During surgery the lesions of parenchymal organs (spleen, pancreas), the intestine and the compression of mesenterium must be avoided. PMID- 26284802 TI - [In Process Citation]. AB - INTRODUCTION: The presence of a substernal goiter which compresses the adjacent structures is per se an indication for resection, mostly total thyreoidectomy should be performed either by a head and neck or general surgeon. In about 1-10% of the cases the goiter is located behind the sternum, and the removal requires different surgical technique. MATERIALS AND METHODS: Authors operated 182 patients between 2000-2014 with substernal goiter which all reached the level of the jugulum. The 182 cases were examined retrospectively. RESULTS: All the patients were symptomatic with choking and dyspnea. In 31 cases neck ultrasound were performed, in 7 cases neck MRI and in 138 cases neck-upper mediastinal CT scan were indicated to discover the real situation of the lobes. 15 patients had previous partial thyreoidectomy. Acervical approach was used in 175 cases, 7 patients required median sternotomy to complete the operation. Transient recurrent laryngeal nerve palsy occurred in 1 patient, permanent RLNP in 3. Nine lesions were malignant, 173 were benign. CONCLUSION: Choking and dyspnea are the most common symptoms of substernal goiter. CT scan is an important preoperative evaluation, while it helps not only to define the position of the thyroid lobes, but also put the right operating team together. Although most of the retrosternal goiters can be removed by a cervical approach, some of them need additional incisions. Hence, it is important to have a thoracic surgeon available. Reviewing the Hungarian literature the authors have not found any other study examining so many patients. PMID- 26284803 TI - [In Process Citation]. AB - CASE PRESENTATION: The authors report the case of a 68-year-old patient who presented with dysphagia 4 months after a mesh-reinforced antireflux surgery. Examinations revealed partial penetration of the mesh into the esophagus. During an expedited surgery, the mesh was removed through thoraco-laparotomy. Distal esophagus and proximal gastric resections were carried out due to longitudinal perforation site and esophageal stricture, and the continuity of the alimentary tract was restored with jejunal interposition. At the 3-month follow-up visit the patient was asymptomatic and a swallow examination showed normal conditions after the surgery. DISCUSSION: Several studies have shown that primary closure of large hiatal hernias is associated with high recurrence rate. In order to reduce this ratio, mesh reinforcement of the crural repair was introduced to prevent reherniation. Therefore, the incidence of recurrence has indeed decreased, however, mesh-related complications have increased. Because of the special anatomical site, the mesh around the gastroesophageal junction is in continuous movement and this can potentially lead to complications such as esophageal erosion, perforation or extensive fibrosis and stenosis. These complications may cause severe, even life-threatening conditions that could only be treated with difficult surgeries. Based on the experience of our case and the review of the literature, we would like to highlight one of the potential, serious complications of mesh-reinforced hiatal repair. PMID- 26284804 TI - [In Process Citation]. PMID- 26284806 TI - [In Process Citation]. PMID- 26284805 TI - [In Process Citation]. PMID- 26284807 TI - Position-Dependent Cardiovascular Response and Time-Motion Analysis During Training Drills and Friendly Matches in Elite Male Basketball Players. AB - The purpose of this study was to measure differences in the cardiovascular workload (heart rate [HR]) and time-motion demands between positional groups, during numerous basketball training drills, and compare the results with in-game competition demands. A convenience sample of 14 top-level professional basketball players from the same club (Spanish First Division, ACB) participated in the study. A total of 146 basketball exercises per player (performed over an 8-week period in 32 team training sessions throughout the competitive season) and 7 friendly matches (FM) played during the preparatory phase were analyzed. The results reveal that HRavg and HRpeak were the highest in FM (158 +/- 10; 198 +/- 9 b . min(-1), respectively). Time-motion analysis showed 1v1 to be the most demanding drill (53 +/- 8 and 46 +/- 12 movements per minute for full and half court, respectively). During FM, players performed 33 +/- 7 movements per minute. Positional differences exist for both HR and time-motion demands, ranging from moderate to very large for all basketball drills compared with FM. Constraints such as number of players, court size, work-to-rest ratios, and coach intervention are key factors influencing cardiovascular responses and time-motion demands during basketball training sessions. These results demonstrate that systematic monitoring of the physical demands and physiological responses during training and competition can inform and potentially improve coaching strategy, basketball-specific training drills, and ultimately, match performance. PMID- 26284808 TI - Well-Defined Thiolated Nanographene as Hole-Transporting Material for Efficient and Stable Perovskite Solar Cells. AB - Perovskite solar cells (PSCs) have been demonstrated as one of the most promising candidates for solar energy harvesting. Here, for the first time, a functionalized nanographene (perthiolated trisulfur-annulated hexa-peri hexabenzocoronene, TSHBC) is employed as the hole transporting material (HTM) in PSCs to achieve efficient charge extraction from perovskite, yielding the best efficiency of 12.8% in pristine form. The efficiency is readily improved up to 14.0% by doping with graphene sheets into TSHBC to enhance the charge transfer. By the HOMO-LUMO level engineering of TSHBC homologues, we demonstrate that the HOMO levels are critical for the performance of PSCs. Moreover, beneficial from the hydrophobic nature of TSHBC, the devices show the improved stability under AM 1.5 illumination in the humidity about 45% without encapsulation. These findings open the opportunities for efficient HTMs based on the functionalized nanographenes utilizing the strong interactions of their functional groups with perovskite. PMID- 26284809 TI - Induction of Apoptosis and Reduction of Endogenous Glutathione Level by the Ethyl Acetate Soluble Fraction of the Methanol Extract of the Roots of Potentilla fulgens in Cancer Cells. AB - Potentilla fulgens root traditionally used as a folk remedy in Meghalaya, India. However, systematic evaluation of its anticancer efficacy was limited. We investigated the anticancer potentials of the various extracts prepared by partitioning of the methanol extract of the root with the aim to discover major contributing factors from the most effective fractions. Methanol extract of P. fulgens roots (PRE) was prepared by maceration which was subsequently fractionated into hexane, ethyl-acetate (EA) and n-butanol soluble fractions. Various assays (clonogenic assay, Flow cytometry analysis, western blot, semiquantitative RT-PCR and the level of endogenous glutathione) were used to evaluate different parameters, such as Cell survivability, PARP-1 proteolysis, expression pattern of anti-apoptotic and gamma-glutamyl-cysteine synthetase heavy subunit (GCSC) genes in both MCF-7 and U87 cancer cell lines. Since the EA fraction showed most efficient growth inhibitory effect, it was further purified and a total of nine compounds and some monomeric and dimeric flavan-3-ols were identified and characterized. Three compounds viz., epicatechin (EC), gallic acid (GA) and ursolic acid (UA) were taken on the basis of their higher yield and 10 MUg/ml of each was mixed together. The concentration used in this study for PRE, EA- and Hex-fraction was 100 MUg/ml, which was higher than the IC50 value. Apoptotic cell death in the PRE, EA-fraction and EC+GA+UA treated cancer cell cultures was significantly greater than in normal cells due to suppression of anti-apoptotic protein Bcl2 following treatment. Depletion of glutathione by downregulating GCSC was also observed. Induction of apoptosis and lowering the level of glutathione are considered to be positive activity for an anticancer agent. Therefore, modulation of GSH concentration in tumor cells by PRE and its EA-fraction opened up the possibility of a new therapeutic approach because these plant products are not harmful to normal cells and may regulate the tumor cellular response to different anticancer treatments. Thus, it would be interesting to examine efficacy of these plant products or EA-fraction in human cancer treatment. PMID- 26284810 TI - LC3B, a Protein That Serves as an Autophagic Marker, Modulates Angiotensin II induced Myocardial Hypertrophy. AB - LC3B is a marker of autophagic activity, and growing evidence supports its importance in myocardial hypertrophy. Thus, regulating LC3B expression may provide an important avenue to inhibit autophagy and protect against or inhibit pathological myocardial hypertrophy. To address this question, we investigated the effects of altering LC3B mRNA expression and autophagic activity in the setting of cardiomyocyte hypertrophy. In an in vitro angiotensin II (Ang II) induced cardiomyocyte hypertrophy model, LC3B mRNA and protein expression was increased and there was activation of cardiomyocyte autophagy, which was assessed by transmission electron microscopy and flow cytometry. LC3B cDNA transfection also resulted in an upregulation of autophagic activity, whereas downregulation of autophagic activity was observed with knockdown of LC3B expression. Induction of LC3B expression was shown to further exacerbate Ang II-stimulated cardiomyocyte hypertrophy, whereas inhibition of LC3B expression inhibited the Ang II-stimulated cardiomyocyte hypertrophy (as assessed through cardiomyocyte morphology and expression of ANP and beta-MHC). This study demonstrated that LC3B modulates the Ang II-induced cardiomyocyte hypertrophy in cultured neonatal rat ventricular cardiomyocytes. PMID- 26284811 TI - Meio- and Macrofaunal Communities in Artificial Water-Filled Tree Holes: Effects of Seasonality, Physical and Chemical Parameters, and Availability of Food Resources. AB - OBJECTIVES: In this study we investigated the dynamics of meiofaunal and macrofaunal communities in artificial water-filled tree holes. The abundances and, for the first time, biomasses and secondary production rates of these communities were examined. The experimental set-up consisted of 300 brown plastic cups placed in temperate mixed forests and sampled five times over a period of 16 months to determine the impact of (i) seasonal events, (ii) physicochemical parameters, and (iii) food resources on the tree hole metazoans. OUTCOMES: Metazoan organisms, especially the meiofauna (rotifers and nematodes) occupied nearly all of the cups (> 99%) throughout the year. Between 55% and 99% of the metazoan community was represented by rotifers (max. 557,000 individuals 100 cm 2) and nematodes (max. 58,000 individuals 100 cm-2). Diptera taxa, particularly Dasyhelea sp. (max. 256 individuals 100 cm-2) dominated the macrofaunal community. Macrofauna accounted for the majority of the metazoan biomass, with a mean dry weight of 5,800 MUg 100 cm-2 and an annual production rate of 20,400 MUg C 100 cm-2, whereas for meiofauna mean biomass and annual production were 100 MUg 100 cm-2 and 5,300 MUg C 100 cm-2, respectively. The macrofaunal taxa tended to show more fluctuating population dynamic while the meiofaunal dynamic was rather low with partly asynchronous development. Seasonality (average temperature and rain intervals) had a significant impact on both meiofauna and macrofauna. Furthermore, bottom-up control (chlorophyll-a and organic carbon), mainly attributable to algae, was a significant factor that shaped the metazoan communities. In contrast, physicochemical water parameters had no evident influence. 23.7% of organism density distribution was explained by redundancy analysis (RDA) indicating a high dynamic and asynchrony of the systems. PMID- 26284812 TI - Current Resources for Evidence-Based Practice, September/October 2015. PMID- 26284814 TI - Methotrexate for topical application in an extemporaneous preparation. AB - BACKGROUND: The antifolate agent methotrexate is routinely used for systemic therapy of cancer and chronic inflammatory diseases. Successful topical use has been described for individual therapeutic attempts, in case series, and small studies, especially for mycosis fungoides (premycotic stage) and lymphomatoid papulosis. With respect to its clinical use in selected treatment scenarios, there have been no approved preparations or regulated instructions for pharmaceutical compounding. MATERIAL AND METHODS: Two high performance liquid chromatography methods were established for the determination of the active substance within a galenic formulation as well as within extracts of biological material. Suitable vehicles for epicutaneous application were developed and preclinically tested for stability, release, and pharmacokinetics of the active substance as well as their safety. RESULTS: The tests show that methotrexate may be readily incorporated into "Basiscreme DAC". It remains stable up to a concentration of 0.5%. This preparation releases enough active substance to achieve relevant local bioavailability in the respective target compartments of the skin. There is no evidence of safety risks due to relevant systemic bioavailability after topical application on a limited area of the skin. CONCLUSIONS: In summary, this approved prescription for extemporaneous preparation complies with the requirements of the German Ordinance on the Operation of Pharmacies (Article 7 ApBetrO), and the available data proves its stability and pharmaceutical quality. PMID- 26284815 TI - The longitudinal impact of depression on disability in Parkinson disease. AB - OBJECTIVE: Depression in Parkinson disease (PD) is a common problem that worsens quality of life and causes disability. However, little is known about the longitudinal impact of depression on disability in PD. This study examined the association between disability and DSM-IV-TR depression status across six years. METHODS: Longitudinal cohort study with assessments at study entry, year two, four, and six conducted in the Morris K. Udall Parkinson Disease Research Center. Recruitment totaled 137 adult men and women with idiopathic PD in which up to six years of data on demographic, motor, and non-motor variables was collected. Movement disorder specialists used the structured interview for DSM-IV-TR depressive disorders and the Northwestern Disability Scale to assess depression and disability. A generalized linear mixed model was fitted with Northwestern Disability Scale score as the dependent variable to determine the effect of baseline depression status on disability. RESULTS: A total of 43 participants were depressed at baseline compared to 94 without depression. Depressed participants were more likely to be female, were less educated, were less likely to take dopamine agonists, and more likely to have motor fluctuations. Controlling for these variables, symptomatic depression predicted greater disability compared to both never depressed (p = 0.0133) and remitted depression (p = 0.0009). Disability associated with symptomatic depression at baseline was greater over the entire six-year period compared to participants with remitted depressive episodes or who were never depressed. CONCLUSIONS: Persisting depression is associated with a long-term adverse impact on daily functioning in PD. Adequate treatment or spontaneous remission of depression improves ADL function. PMID- 26284816 TI - The Impact of Playworks on Students' Physical Activity by Race/Ethnicity: Findings from a Randomized Controlled Trial. AB - BACKGROUND: The Playworks program places coaches in low-income urban schools to engage students in physical activity during recess. The purpose of this study was to estimate the impact of Playworks on students' physical activity separately for Hispanic, non-Hispanic black, and non-Hispanic white students. METHODS: Twenty seven schools from 6 cities were randomly assigned to treatment and control groups. Accelerometers were used to measure the intensity of students' physical activity, the number of steps taken, and the percentage of time in moderate-to vigorous physical activity (MVPA) during recess. The impact of Playworks was estimated by comparing average physical activity outcomes in treatment and control groups. RESULTS: Compared with non-Hispanic black students in control schools, non-Hispanic black students in Playworks schools recorded 338 more intensity counts per minute, 4.9 more steps per minute, and 6.3 percentage points more time in MVPA during recess. Playworks also had an impact on the number of steps per minute during recess for Hispanic students but no significant impact on the physical activity of non-Hispanic white students. CONCLUSIONS: The impact of Playworks was larger among minority students than among non-Hispanic white students. One possible explanation is that minority students in non-Playworks schools typically engaged in less physical activity, suggesting that there is more room for improvement. PMID- 26284817 TI - Why Do Physiotherapists Do What They Do? A Study of Kuwaiti Physiotherapists. AB - BACKGROUND AND PURPOSE: Physiotherapy has an important role in the management of numerous musculoskeletal (MSK) problems. In terms of evidence-based physiotherapy practice, little is known about the reasons for selection of treatment techniques by MSK physiotherapists or whether their treatments are evidence based. This survey aimed to explore the reasons for the choice of treatment techniques by Kuwaiti MSK physiotherapists and to identify the extent of using the evidence base from research findings as a basis for physiotherapy practice. METHODS: A self-reported questionnaire accompanied with participant information sheet was distributed to 139 MSK physiotherapists in seven hospitals in Kuwait. The questionnaire was modified from that used in a previous study for use with Kuwaiti MSK physiotherapists to include modalities that were known to be used there by the lead author. It was piloted prior to distribution on three Kuwaiti MSc students for content and face validity. RESULTS: One hundred six of 139 therapists responded, of whom 22% were male and 78% were female. The study showed that undergraduate education was the main influence for all treatment techniques used by Kuwaiti MSK physiotherapists. The use of research findings as a basis for choice of treatment techniques was very limited. The use of research was not related to post-qualification education or years of professional experience. CONCLUSION: The findings of this study demonstrate that current physiotherapy practice in Kuwait is more reliant on undergraduate education and less on research evidence for the choice of treatment techniques. This has implications for undergraduate physiotherapy curricula, suggesting that evidence-based practice must be keenly espoused. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26284818 TI - Is it really worth adapting liver stiffness cut-offs according to AST levels? PMID- 26284819 TI - Protein Kinase C Isoforms Differentially Regulate Hypoxia-Inducible Factor-1alpha Accumulation in Cancer Cells. AB - Hypoxia-inducible factor-1alpha (HIF-1alpha) is one of the key transcription factors that mediate adaptation to hypoxia. Despite increasing evidence implicating the PKC family as potential modulators of HIF-1alpha, the molecular mechanisms of PKC isoform-dependent HIF-1alpha activity under hypoxic conditions have not been systematically elucidated in cancer cell lines. Here, we collectively investigated how each isoform of the PKC family contributes to HIF 1alpha accumulation in the human cervical cancer cell line HeLa. Among the abundant PKC isoforms, blockade of either PKCalpha or PKCdelta was found to substantially reduce HIF-1alpha accumulation and transcriptional activity in hypoxic cells. Knockdown of PKCdelta resulted in a reduction of HIF-1alpha mRNA levels, whereas the HIF-1alpha mRNA level was unchanged regardless of PKCalpha knockdown. Upon searching for the downstream effectors of these kinases, we found that PKCalpha controls HIF-1alpha translation via AKT-mTOR under hypoxic conditions. On the other hand, one of the well-known transcriptional regulation pathways of HIF-1alpha, nuclear factor-kappaB (NF-kappaB) is identified as a downstream effector of PKCdelta. Taken together, our findings provide insights into the roles of PKC isoforms as additional, discrete modulators of hypoxia stimulated HIF-1alpha accumulation through different signaling pathways. PMID- 26284820 TI - New density functional parameterizations to accurate calculations of electric field gradient variations among compounds. AB - This research provides a performance investigation of density functional theory and also proposes new functional parameterizations to deal with electric field gradient (EFG) calculations at nuclear positions. The entire procedure is conducted within the four-component formalism. First, we noticed that traditional hybrid and long-range corrected functionals are more efficient in the description of EFG variations for a set of elements (indium, antimony, iodine, lutetium, and hafnium) among linear molecules. Thus, we selected the PBE0, B3LYP, and CAM-B3LYP functionals and promoted a reoptimization of their parameters for a better description of these EFG changes. The PBE0q variant developed here showed an overall promising performance in a validation test conducted with potassium, iodine, copper, and gold. In general, the correlation coefficients found in linear regressions between experimental nuclear quadrupole coupling constants and calculated EFGs are improved while the systematic EFG errors also decrease as a result of this reparameterization. PMID- 26284821 TI - Donor-specific alloantibodies in liver transplantation: how should we define and improve long-term success? PMID- 26284813 TI - Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations. AB - Polycystic ovary syndrome (PCOS) is a common, highly heritable complex disorder of unknown aetiology characterized by hyperandrogenism, chronic anovulation and defects in glucose homeostasis. Increased luteinizing hormone relative to follicle-stimulating hormone secretion, insulin resistance and developmental exposure to androgens are hypothesized to play a causal role in PCOS. Here we map common genetic susceptibility loci in European ancestry women for the National Institutes of Health PCOS phenotype, which confers the highest risk for metabolic morbidities, as well as reproductive hormone levels. Three loci reach genome-wide significance in the case-control meta-analysis, two novel loci mapping to chr 8p23.1 [Corrected] and chr 11p14.1, and a chr 9q22.32 locus previously found in Chinese PCOS. The same chr 11p14.1 SNP, rs11031006, in the region of the follicle stimulating hormone B polypeptide (FSHB) gene strongly associates with PCOS diagnosis and luteinizing hormone levels. These findings implicate neuroendocrine changes in disease pathogenesis. PMID- 26284822 TI - Genomic scanning using AFLP to detect loci under selection in the moss Funaria hygrometrica along a climate gradient in the Sierra Nevada Mountains, Spain. AB - The common cord moss Funaria hygrometrica has a worldwide distribution and thrives in a wide variety of environments. Here, we studied the genetic diversity in F. hygrometrica along an abiotic gradient in the Mediterranean high mountain of Sierra Nevada (Spain) using a genome scan method. Eighty-four samples from 17 locations from 24 to 2700 m were fingerprinted based on their amplified fragment length polymorphism (AFLP) banding pattern. Using PCA and Bayesian inference we found that the genetic diversity was structured in three or four clusters, respectively. Using a genome scan method we identified 13 outlier loci, which showed a signature of positive selection. Partial Mantel tests were performed between the Euclidean distance matrices of geographic and climatic variables, versus the pair-wise genetic distance of the AFLP dataset and AFLP-positive outliers dataset. AFLP-positive outlier data were significantly correlated with the gradient of the climatic variables, suggesting adaptive variation among populations of F. hygrometrica along the Sierra Nevada Mountains. We highlight the additional analyses necessary to identify the nature of these loci, and their biological role in the adaptation process. PMID- 26284824 TI - Factors Contributing to Inappropriate Visits of Frequent Attenders and Their Economic Effects at an Emergency Department in Singapore. AB - OBJECTIVES: This study aimed to determine which factors contribute to frequent visits at the emergency department (ED) and what proportion were inappropriate in comparison with nonfrequent visits. METHODS: This study was a retrospective, case control study comparing a random sample of frequent attenders and nonfrequent attenders, with details of their ED visits recorded over a 12-month duration. Frequent attenders were defined as patients with four or more visits during the study period. RESULTS: In comparison with nonfrequent attenders (median age = 45.0 years, interquartile range [IQR] = 28.0 to 61.0 years), frequent attenders were older (median = 57.5 years, IQR = 34.0 to 74.8 years; p = 0.0003). They were also found to have more comorbidities, where 53.3% of frequent attenders had three or more chronic illnesses compared to 14% of nonfrequent attenders (p < 0.0001), and were often triaged to higher priority (more severe) classes (frequent 52.2% vs. nonfrequent 37.6%, p = 0.0004). Social issues such as bad debts (12.7%), heavy drinking (3.3%), and substance abuse (2.7%) were very low in frequent attenders compared to Western studies. Frequent attenders had a similar rate of appropriate visits to the ED as nonfrequent attenders (55.2% vs. 48.1%, p = 0.0892), but were more often triaged to P1 priority triage class (6.7% vs. 3.2%, p = 0.0014) and were more often admitted for further management compared to nonfrequent attenders (47.5% vs. 29.6%, p < 0.001). The majority of frequent attender visits were appropriate (55.2%), and of these, 81.1% resulted in admission. For the same number of patients, total visits made by frequent attenders ($174,247.60) cost four times as much as for nonfrequent attenders ($40,912.40). This represents a significant economic burden on the health care system. CONCLUSIONS: ED frequent attenders in Singapore were associated with higher age and presence of multiple comorbidities rather than with social causes of ED use. Even in integrated health systems, repeat ED visits are frequent and expensive, despite minimal social causes of acute care. EDs in aging populations must anticipate the influx of vulnerable, elderly patients and have in place interventional programs to care for them. PMID- 26284823 TI - Lenalidomide is safe and active in Waldenstrom macroglobulinemia. AB - Lenalidomide is manageable and effective in multiple myeloma, particularly in elderly patients. Surprisingly, the combination of lenalidomide with rituximab produced clinically significant anemia at 25 mg/day for 21/28 days, the highest possible dose, in Waldenstrom's Macroglobulinemia (WM). We aimed to determine the maximum tolerated dose (MTD) of single agent lenalidomide and determine its impact on WM. RV-WM-0426 is a multicenter dose escalation open label phase 1/2 study of lenalidomide in relapsed/refractory WM (RRWM). Lenalidomide was given orally 21/28 days per cycle for 1 year, at escalated dose of 15 to 20 mg during phase 1 to determine the MTD; the phase 2 part was conducted at the MTD. Seventeen RRWM patients were included. The MTD was established at 15 mg/day 21/28. By ITT analysis, the overall response rate was 29%. With a median follow up of 36 months, median TTP was 16 months (95% CI 5.5-26), the 5-year OS was 91%. The most frequent adverse events >= grade 3 at 15 mg were 14% anemia and 43% neutropenia. The MTD of lenalidomide is 15 mg/day 21/28 days in RRWM. Lenalidomide is active in the treatment of RRWM and the safety profile appears manageable. Future studies may look into combinations of lenalidomide and continuous dosing. PMID- 26284825 TI - The curious case of the exploding spleen! PMID- 26284826 TI - Data management and archiving in a large microscopy-and-imaging, multi-user facility: Problems and solutions. AB - Advancements in microscopy and imaging have pushed the boundaries of what was once thought possible in many fields of research. New techniques, coupled with the application of new technologies, allow researchers to answer increasingly complex questions by probing deeper and with greater accuracy. While, these new techniques provide far greater specificity and increased sensitivity in regards to both resolution and frequency, the amount of data generated is swelling to a point where conventional data-management systems struggle to keep pace; this is especially true for large microscopy-and-imaging shared-user facilities. Sub optimal data management can severely hinder the ability of a researcher to determine experimental results accurately or efficiently, and will inevitably limit the functionality of the research facility itself. This review discusses the source of the problem: how data are produced by systems available today, and the information's specificity and relative importance; techniques for management of these data to maximize functionality of the facility; and practices that can be detrimental in the research core environment. PMID- 26284827 TI - Oxidative Nitration of Styrenes for the Recycling of Low-Concentrated Nitrogen Dioxide in Air. AB - The oxidative nitration of styrenes in ethyl acetate represents a metal-free, environmentally friendly, and sustainable technique to recover even low concentrations of NO2 in air. Favorable features are that the product mixture comprising nitroalcohols, nitroketones, and nitro nitrates simplifies at lower concentrations of NO2 . Experiments in a miniplant-type 10 L wet scrubber demonstrated that the recycling technique is well applicable on larger scales at which initial NO2 concentrations of >10 000 ppm were reliably reduced to less than 40 ppm. PMID- 26284828 TI - De novo fatty acid biosynthesis and elongation in very long-chain acyl-CoA dehydrogenase-deficient mice supplemented with odd or even medium-chain fatty acids. AB - An even medium-chain triglyceride (MCT)-based diet is the mainstay of treatment in very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD). Previous studies with magnetic resonance spectroscopy have shown an impact of MCT on the average fatty acid chain length in abdominal fat. We therefore assume that medium chain fatty acids (MCFAs) are elongated and accumulate in tissue as long-chain fatty acids. In this study, we explored the hepatic effects of long-term supplementation with MCT or triheptanoin, an odd-chain C7-based triglyceride, in wild-type and VLCAD-deficient (VLCAD(-/-) ) mice after 1 year of supplementation as compared with a control diet. The de novo biosynthesis and elongation of fatty acids, and peroxisomal beta-oxidation, were quantified by RT-PCR. This was followed by a comprehensive analysis of hepatic and cardiac fatty acid profiles by GC-MS. Long-term application of even and odd MCFAs strongly induced de novo biosynthesis and elongation of fatty acids in both wild-type and VLCAD(-/-) mice, leading to an alteration of the hepatic fatty acid profiles. We detected de novo synthesized and elongated fatty acids, such as heptadecenoic acid (C17:1n9), eicosanoic acid (C20:1n9), erucic acid (C22:1n9), and mead acid (C20:3n9), that were otherwise completely absent in mice under control conditions. In parallel, the content of monounsaturated fatty acids was massively increased. Furthermore, we observed strong upregulation of peroxisomal beta-oxidation in VLCAD(-/-) mice, especially when they were fed an MCT diet. Our data raise the question of whether long-term MCFA supplementation represents the most efficient treatment in the long term. Studies on the hepatic toxicity of triheptanoin are still ongoing. PMID- 26284829 TI - Genetic and environmental contributions to the inverse association between specific autistic traits and experience seeking in adults. AB - Autistic traits are characterized by social and communication problems, restricted, repetitive and stereotyped patterns of behavior, interests and activities. The relation between autistic traits and personality characteristics is largely unknown. This study focused on the relation between five specific autistic traits measured with the abridged version of the Autism Spectrum Quotient ("social problems," "preference for routine," "attentional switching difficulties," "imagination impairments," "fascination for numbers and patterns") and Experience Seeking (ES) in a general population sample of adults, and subsequently investigated the genetic and environmental etiology between these traits. Self-reported data on autistic traits and ES were collected in a population sample (n = 559) of unrelated individuals, and in a population based family sample of twins and siblings (n = 560). Phenotypic, genetic and environmental associations between traits were examined in a bivariate model, accounting for sex and age differences. Phenotypically, ES correlated significantly with "preference for routine" and "imagination impairments" in both samples but was unrelated to the other autistic traits. Genetic analyses in the family sample revealed that the association between ES and "preference for routine" and "imagination impairments" could largely be explained by a shared genetic factor (89% and 70%, respectively). Our analyses demonstrated at a phenotypic and genetic level an inverse relationship between ES and specific autistic traits in adults. ES is associated with risk taking behavior such as substance abuse, antisocial behavior and financial problems. Future research could investigate whether autistic traits, in particular strong routine preference and impaired imagination skills, serve as protective factors for such risky behaviors. (c) 2015 Wiley Periodicals, Inc. PMID- 26284830 TI - Human hair follicle organ culture: theory, application and perspectives. AB - For almost a quarter of a century, ex vivo studies of human scalp hair follicles (HFs) have permitted major advances in hair research, spanning diverse fields such as chronobiology, endocrinology, immunology, metabolism, mitochondrial biology, neurobiology, pharmacology, pigmentation and stem cell biology. Despite this, a comprehensive methodological guide to serum-free human HF organ culture (HFOC) that facilitates the selection and analysis of standard HF biological parameters and points out both research opportunities and pitfalls to newcomers to the field is still lacking. The current methods review aims to close an important gap in the literature and attempts to promote standardisation of human HFOC. We provide basic information outlining the establishment of HFOC through to detailed descriptions of the analysis of standard read-out parameters alongside practical examples. The guide closes by pointing out how serum-free HFOC can be utilised optimally to obtain previously inaccessible insights into human HF biology and pathology that are of interest to experimental dermatologists, geneticists, developmental biologists and (neuro-) endocrinologists alike and by highlighting novel applications of the model, including gene silencing and gene expression profiling of defined, laser capture-microdissected HF compartments. PMID- 26284831 TI - Measuring Maternal Health Literacy in Adolescents Attending Antenatal Care in Uganda: Exploring the Dimensionality of the Health Literacy Concept Studying a Composite Scale. AB - BACKGROUND AND PURPOSE: The purpose of this article is to test the requirement of "local independence" in the newly developed "Maternal Health Literacy" (MaHeLi) composite scale measuring health literacy in pregnant adolescents attending antenatal care. METHODS: The 20-item scale was administered to 384 adolescents aged 15-19 years attending antenatal care in Uganda during the period July December 2013. Rasch analysis was conducted using RUMM2030. RESULTS: Differential item functioning was observed for 3 items. One item had disordered response categories. One subscale brought substantial multidimensionality into the MaHeLi scale. CONCLUSIONS: Results support the use of a 12-item version of the MaHeLi scale. The article shows how Rasch analyses help us to identify violations of local independence in scales. PMID- 26284832 TI - Determining Intervention Fidelity From Chronological Field Notes. AB - BACKGROUND AND PURPOSE: Intervention fidelity (IF) is a relatively recent methodological consideration in nursing research that refers to the adherent and competent behaviors by the interventionist. The purpose of this study was to explore an alternative method of determining IF using chronological field notes (CFNs). METHOD: A secondary analysis using data from an intervention study. A randomly selected sample of CFNs (N = 181) written by interventionist nurses (N = 20) were coded using the Collaborative Study Psychotherapy Rating Scale, a validated fidelity instrument used in similar studies. RESULTS: The study provides no evidence that the field notes could be used for determining intervention fidelity. CONCLUSION: Further research is needed on IF that would provide less intrusive an alternate method. PMID- 26284833 TI - The Useful Depression Screening Tool for Older Adults: Psychometric Properties and Clinical Applicability. AB - BACKGROUND AND PURPOSE: The purpose of this study is to test the reliability and validity of the 3-item Useful Depression Screening Tool (UDST) for use with older adults in congregate living settings. METHODS: There were 176 residents of senior housing or assisted living who completed the UDST. Rasch analysis and test criterion relationships with pain, physical activity, and depression diagnosis were used to determine validity. Test-retest reliability was conducted with 29 senior housing residents. RESULTS: Rasch analysis demonstrated good fit of all items to the concept of depression. Criterion validity was supported, F(5) = 14.17, p < .001. Test-retest showed no significant differences in UDST scores over time (p = .29). CONCLUSIONS: The findings provide support for the validity and reliability of the UDST for use with older adults in congregate living settings. PMID- 26284834 TI - Adaptation and Validation of the Learning Style Inventory Version 3.1 in Greek Language: A Methodological Study. AB - BACKGROUND AND PURPOSE: The nursing research on learning differences is currently expanding, suggesting the need for trustful measurements. This study aimed to adapt and cross-culturally validate the Learning Style Inventory. METHODS: The first phase involved symmetrical translation and adaptation to the Greek target language. The second phase concerned the psychometric testing. RESULTS: Internal reliability showed satisfactory alpha values. Kappa coefficients supported the test-retest reliability, and paired t test correlations justified the stability. Factor analysis yielded 2 constructs fitted with theory. The internal validity was also evidenced. The nursing students' learning style profile was discussed within their educational field and cultural background. CONCLUSIONS: The inventory presented content and construct equivalence to original scales. Certain implications were drawn for nursing supporting the utility of learning styles' measurements. PMID- 26284835 TI - I would like to give a huge "thank you" to everyone who has submitted, reviewed,and published in the Journal of Nursing Measurement. Introduction. PMID- 26284836 TI - Psychometric Testing of a Comprehensive Patient Satisfaction Survey in Arabic. AB - BACKGROUND AND PURPOSE: Although patient satisfaction is an important indicator of the quality of care received in hospitals, no reliable and valid Arabic comprehensive inpatient satisfaction survey has been published. The purpose of this study was to evaluate the psychometric properties of an Arabic patient satisfaction survey. METHODS: A cross-sectional design was used where 1,339 randomly selected patients were interviewed by phone. The questionnaire was adopted and from the Hospital Consumer Assessment of Healthcare Providers and Systems survey, refined and tested over a 4-year period. RESULTS: Item-item correlations for the 22 items on the survey ranged from .52 to .92, and the Cronbach's alpha coefficient was .87. Construct and predictive validity were also adequate. CONCLUSION: The survey is recommended for use in hospitals in Lebanon and other Middle Eastern countries to facilitate benchmarking and quality improvement. PMID- 26284837 TI - Development and Preliminary Validation of the Adherence to Weight Control Questionnaire. AB - BACKGROUND AND PURPOSE: This study tests the psychometric properties of the Adherence to Weight Control Questionnaire, a new screening tool to measure treatment adherence (TAWC) and the risk of nonadherence to weight control (RNAWC) in adolescents. METHODS: Participants are 92 adolescents (12-18 years old) from a pediatric obesity clinic. Construct validity were evaluated using a principal axis factoring method with varimax rotation. Reliability and criterion-related validity of both scales were also checked. RESULTS: Both scales presented good reliability values (.770 and .908). Statistical analyses yielded a 1-factor solution for the RNAWC and a 4-factor solution for the TAWC. Criterion-related validity of scales was also checked. CONCLUSIONS: Results showed that this theory driven measure of adherence to weight control has adequate psychometric properties to support both research and the clinical practice. PMID- 26284838 TI - Reliability and Validity of a Tool to Measure School Nurse Perceptions and Practices Associated With Childhood Obesity Prevention. AB - BACKGROUND AND PURPOSE: Childhood obesity prevention (COP) should include increasing school nurse involvement. Measurements of school nurse perceptions influencing COP practices are limited. The purpose of this study is to evaluate the reliability and validity of 5 measures of school nurse COP practices and perceptions. METHODS: A 70-item anonymous survey was completed by 171 Florida registered nurse (RN) school nurses and tested for reliability and validity. RESULTS: Internal reliability was acceptable with Cronbach's alphas ranging from .81 to .94. Uncertain to adequate test-retest reliability was determined by correlation coefficients (r = .55-.78). Significant correlations (p < .05) based on hypothesized relationships provided moderate support for construct validity. CONCLUSIONS: Results support use of these scales in research with targeted school nurse populations to promote COP practices. PMID- 26284839 TI - Measuring Care Needs of Parents of Children With Cancer: Psychometric Properties of the FIN-PED II Arabic Version. AB - BACKGROUND AND PURPOSE: This study was conducted to test the Arabic version of the Family Inventory of Needs-Pediatrics II (FIN-PED II). METHODS: The Arabic FIN PED II was developed using the translation/back-translation method. Then, an expert panel of 5 parents of children with cancer rated the tool for clarity and content validity. Internal consistency and test-retest reliability was evaluated in a convenience sample of 113 parents of children with cancer. RESULTS: The FIN PED II was found to be acceptable and clear to almost all parents. The FIN-PED II demonstrated good psychometric properties. The internal consistency was high with alpha values > 0.70 and high test-retest correlations. CONCLUSIONS: Although the Arabic FIN-PED II needs further psychometric testing, it is an acceptable, reliable, and valid measure of perceived parents need during child's treatment. PMID- 26284840 TI - Measuring Physical Activity of Elementary School Children With Unsealed Pedometers: Compliance, Reliability, and Reactivity. AB - BACKGROUND AND PURPOSE: Evidence of compliance, reliability, and reactivity of using pedometers in children remains inconsistent. This study aimed to examine these aspects of unsealed pedometers. METHODS: There were 133 children who wore pedometers for 7 days. A subsample of 50 children completed surveys measuring self-efficacy, enjoyment, parental influence, and environment on Day 1 and 8. Investigator presence and incentives were used to increase compliance. RESULTS: About 87% of children returned pedometers, with 62% wearing pedometers for 4 days or longer. The intraclass correlation coefficients ranged from .70 to .87, with ICC for 4-day pedometer steps exceeding .80. Wearing pedometers did not change pedometer steps nor alter children's perceptions of self-efficacy, enjoyment, parental influence, and environment significantly. CONCLUSIONS: Children were compliant wearing pedometers, and there was no reactivity from wearing them. PMID- 26284841 TI - Measuring Nurse Attitudes About Childbirth: Revision and Pilot Testing of the Nurse Attitudes and Beliefs Questionnaire. AB - BACKGROUND AND PURPOSE: Labor/delivery nurse attitudes and beliefs may affect nursing care decisions and patient outcomes. This psychometric study was conducted to revise the Nurse Attitudes and Beliefs Questionnaire-Revised (NABQ R). METHODS: The NABQ-R contains 42 items scored with a 4-point Likert scale from 1 (strongly disagree) to 4 (strongly agree). An online survey invitation was sent to Colorado intrapartum nurses with 84 complete surveys returned. RESULTS: The NABQ-R scores ranged from 82 to 156 and the Cronbach's alpha was .90. An exploratory factor analysis was conducted, and all items loaded on at least 1 factor. CONCLUSIONS: Our results support acceptable initial psychometric properties for the NABQ-R consistent with existing theory indicating that the NABQ-R shows promise for use in future studies. PMID- 26284842 TI - Assessing Longitudinal Invariance of the Center for Epidemiologic Studies Depression Scale Among Middle-Aged and Older Adults. AB - BACKGROUND AND PURPOSE: The longitudinal invariance of the Center for Epidemiologic Studies-Depression (CES-D) scale among middle-aged and older adults is unknown. This study examined the factorial invariance of the CES-D scale in a large cohort of community-based adults longitudinally. METHODS: 1,204 participants completed the 20-item CES-D scale at 4 time points 1 year apart. Structural equation modeling was used to identify best fitting model using longitudinal data at baseline and at 1-, 2-, and 3-year follow-up. RESULTS: The 4 factor model showed partial invariance over 3 years. Two of the 6 noninvariant items were consistently noninvariant at the 3 follow-up points. CONCLUSION: Special consideration should be given to these 2 items when using the CES-D scale in healthy adults (45-75 years old). PMID- 26284843 TI - Psychometric Properties of Newly Translated Spanish Life Events Inventory and Daily Hassles Scale. AB - BACKGROUND AND PURPOSE: Measuring stress in Hispanic Americans, the fastest growing U.S. minority, is problematic. The Life Events Inventory (LEI) and the Daily Hassles Scale (DHS), widely used stress instruments, are not available in Spanish. PURPOSE: To test the psychometric properties of the translated Spanish versions of the LEI and DHS. METHODS: A convenience sample of 63 Hispanic women completed both instruments in Spanish and English 2 weeks apart. RESULTS: Internal consistency reliability and stability were strong for both instruments (.85-.97). Reliability and validity evidence for the translated Spanish versions were strong and similar to the English version. CONCLUSIONS: Psychometric findings suggest that the newly translated Spanish versions are good representations of the English versions and that these newly translated instruments are ready for use. PMID- 26284844 TI - Reliability and Validity of a Shortened Version of an Instrument for Diabetes Self-Care Agency. AB - PURPOSE: The purpose of this study was to develop a shortened version of the Instrument of Diabetes Self-Care Agency (IDSCA). METHODS: In the development of the shortened version of IDSCA, intraclass correlation coefficient 2 (ICC2) analysis was done to determine items to be deleted. However, the 7 subscales were retained. The shortened IDSCA was evaluated for internal consistency, reproducibility, concurrent validity, criterion-related validity, and goodness of fit. RESULTS: The shortened IDSCA included 35 items addressing 7 subscales. High ICC2 (.804) and a high Cronbach's alpha (.89) indicate internal consistency and reproducibility. A high correlation (.62) between the shortened version of the IDSCA and the Self-Care Agency Questionnaire indicated concurrent validity. CONCLUSION: The shortened IDSCA provides a reliable and valid measure of self care agency of individuals with diabetes. PMID- 26284845 TI - Assessment of Insulin Administration Methods: Perceptions by Patients and Significant Others Instrument Development. AB - BACKGROUND AND PURPOSE: To develop, test, and establish the validity and reliability of 4 instruments to evaluate perceptions of paired patients and patient-identified significant others to assess the impact of continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injections (MDII) on diabetes management and lifestyle. METHODS: Sociotechnical systems theory and the life patterns model framed the study. Four parallel survey instruments (patient CSII and MDII and significant other CSII and MDII) were developed to elicit demographic information and perceptions concerning CSII and MDII. RESULTS: Validity and reliability were established. CONCLUSIONS: The instruments developed for this study could be adapted or used as templates in management approach impact studies of other chronic diseases. The study should be replicated with a different geographic sample. PMID- 26284846 TI - Preliminary Reliability and Validity of an Exercise Benefits and Barriers for Stroke Prevention Scale in an African American Sample. AB - BACKGROUND AND PURPOSE: African Americans are at heightened risk of first stroke, and regular exercise can reduce stroke risk. Benefits and barriers to exercise subscales from 2 instruments were combined to create the Exercise Benefits and Barriers for Stroke Prevention (EBBSP) scale. METHODS: Reliability and validity of the EBBSP scale were examined in a nonrandom sample of 66 African Americans who were primarily female, average age 43.3 +/- 9.4 years, and high school graduates. RESULTS: Both subscales had adequate internal consistency reliability. Factor analysis revealed two factors for each subscale. More benefits and fewer perceived barriers were significantly related to current exercise and future intentions to exercise. CONCLUSIONS: The EBBSP scale may be useful in research focused on understanding, predicting, and promoting exercise for stroke prevention in adults. PMID- 26284847 TI - Effect of Head Position on Facial Soft Tissue Depth Measurements Obtained Using Computed Tomography. AB - Facial soft tissue depth (FSTD) studies employing clinical computed tomography (CT) data frequently rely on depth measurements from raw 2D orthoslices. However, the position of each patient's head was not standardized in this method, potentially decreasing measurement reliability and accuracy. This study measured FSTDs along the original orthoslice plane and compared these measurements to those standardized by the Frankfurt horizontal (FH). Subadult cranial CT scans (n = 115) were used to measure FSTDs at 18 landmarks. Significant differences were observed between the methods at eight of these landmarks (p < 0.05), demonstrating that high-quality data are not generated simply by employing modern imaging modalities such as CT. Proper technique is crucial to useful results, and maintaining control over head position during FSTD data collection is important. This is easily and most readily achieved in CT techniques by rotating the head to the FH plane after constructing a 3D rendering of the data. PMID- 26284848 TI - Discussing endogenous NO(*)/HNO interconversion aided by phenolic drugs and vitamins. AB - The reduction of NO(*) to HNO/NO(-) under biologically compatible conditions has always been thought as unlikely, mostly because of the negative reduction potential: E degrees (NO(*),H(+)/HNO) = -0.55 V vs NHE at physiological pH. Nonetheless, during the past decade, several works hinted at the possible NO-to HNO conversion mediated by moderate biological reductants. Very recently, we have shown that the reaction of NO(*) with ascorbate and aromatic alcohols occurs through a proton-coupled nucleophilic attack (PCNA) of the alcohol to NO(*), yielding an intermediate RO-N(H)O(*) species, which further decomposes to release HNO. For the present work, we decided to inspect whether other common biological aromatic alcohols obtained from foods, such as Vitamin E, or used as over-the counter drugs, like aspirin, are able to undergo the reaction. The positive results suggest that the conversion of NO to HNO could occur far more commonly than previously expected. Taking these as the starting point, we set to review our and other groups' previous reports on the possible NO-to-HNO conversion mediated by biological compounds including phenolic drugs and vitamins, as well as several thiol-bearing compounds. Analysis of revised data prompted us to ask ourselves the following key questions: What are the most likely physio/pathological conditions for NO(*)-to-HNO conversion to take place? Which effects usually attributed to NO(*) are indeed mediated by HNO? These inquiries are discussed in the context of 2 decades of NO and HNO research. PMID- 26284853 TI - Unlucky year thirteen for Needham's Odd Fellows Building: did Leach's ether contribute to the conflagration? PMID- 26284849 TI - Resveratrol in the treatment of pancreatic cancer. AB - Pancreatic cancer (PCa), which is now the fourth most frequent cause of cancer related death, has a median survival of less than 6 months and a 5-year survival rate of <6%. The hallmarks of this cancer include poor outcome, short survival duration, and resistance to therapy. The poor prognosis of PCa is related to its local recurrence, lymph node and liver metastases, and peritoneal dissemination. Recent studies have indicated that resveratrol has cancer-chemopreventive and anticancer activities. In this short review we summarize the chemopreventive and treatment effects of resveratrol in PCa, as follows: resveratrol inhibits the proliferation of pancreatic cancer cells; induces apoptosis and cell cycle arrest; inhibits metastasis and invasion of PCa cells; inhibits the proliferation and viability of PCa stem cells; enhances the chemoradiosensitization of PCa cells; and can affect diabetes mellitus in addition to PCa. On the basis of these data, resveratrol may be considered a potential anticancer agent for the treatment of PCa. PMID- 26284854 TI - Paul Meyer Wood's parents at "The Biblical Seminary in New York". PMID- 26284855 TI - Labat and the Anglo-French drug company's Neocaine. PMID- 26284856 TI - Insufficient proof of concept for using ultrasound to guide fluid resuscitation. PMID- 26284857 TI - Lack of evidence for the use of ultrasound B-line artifacts to guide fluid resuscitation. PMID- 26284858 TI - Inappropriate use of B-lines for fluid assessment and management in intensive care patients. PMID- 26284859 TI - In reply. PMID- 26284860 TI - Benefits of adding sciatic nerve block to femoral nerve block for total knee arthroplasty. PMID- 26284861 TI - In reply. PMID- 26284862 TI - Propofol-induced electroencephalogram dynamics: a missing piece. PMID- 26284863 TI - In reply. PMID- 26284864 TI - Perioperative care of the elderly patient with hip fracture. PMID- 26284865 TI - In reply. PMID- 26284866 TI - In reply. PMID- 26284867 TI - Questions regarding the diagnosis of malignant hyperthermia. PMID- 26284868 TI - In reply. PMID- 26284869 TI - Effect of lateral tilt angle on the volume of the abdominal aorta and inferior vena cava in pregnant and nonpregnant women determined by magnetic resonance imaging. PMID- 26284870 TI - In reply. PMID- 26284871 TI - Anaphylaxis incidence with rocuronium, succinylcholine, and atracurium: how risk communication can influence behavior. PMID- 26284877 TI - Anesthesiologists & Ultrasonography: A Historical Window. PMID- 26284878 TI - Scaffolded multimers of hIAPP(20-29) peptide fragments fibrillate faster and lead to different fibrils compared to the free hIAPP(20-29) peptide fragment. AB - Applying fibril-forming peptides in nanomaterial design is still challenged by the difficulties in understanding and controlling how fibrils form. The present work investigates the influence of motional restriction on peptide fibrillation. We use cyclotriphosphazene and cyclodextrin as templates to make conjugates of the fibril-forming core of human islet amyloid polypeptide. Attachment of the peptide to the templates resulted in multimers containing six peptide fragments at different positions. ThT fluorescence, CD and FTIR spectroscopy, and AFM and TEM imaging reveal that in both conjugates the peptide retained its fibrillating properties and formed fibrils. However, the conjugate fibrils formed more rapidly than the free peptide and were long and thin, as opposed to the thick and twisted morphology of the intact peptide. Thus the motional restrictions introduced by the scaffold modulate the structure of the fibrils but do not impede the actual fibrillation process. PMID- 26284879 TI - ["Would I get there in time, or would the disease already have run it's course?". The provincial doctor fought against the Spanish flu in the forest districts of Jamtland]. PMID- 26284880 TI - [Death is delayed--but it arrives soon]. PMID- 26284881 TI - [Foreign-born report more problems after total hip arthroplasty than Swedish born. Unclear why, but better informed and educated interpreters may be needed]. AB - In 2013, 23.3% of the Swedish population of 9.7 million had foreign background and 15.4% were born outside the country. Immigrants, just as natives, suffer or will suffer from hip disease, which could involve surgery with total hip arthroplasty. Our aim was to explore the association between birthplace (in or outside Sweden), socio-economic factors and outcome after primary total hip arthroplasty. Records from the Swedish Hip Arthroplasty Register were cross matched with population-based registers from the National Board of Health and Welfare and Statistics Sweden. Preoperatively immigrants reported more problems with self-care (P<=0.02), usual activities (P<=0.05) and anxiety/depression (P<=0.005) as well as higher levels of pain. Postoperatively immigrants reported more problems in all EQ-5D dimensions. Improved patient information, better training of medical staff and better access to interpreters could facilitate these patients' contacts with health care and also contribute to improved outcome. PMID- 26284882 TI - [Knowledge of the cultural aspects of health is key to equitable care]. PMID- 26284883 TI - [Serrated polyps is a hidden but common cause of colorectal cancer]. AB - The concept that serrated polyps can cause colorectal cancer is relatively new and not very well-known. Serrated polyps are difficult to identify and treat endoscopically. This together with the fact that premalignant serrated polyps are mainly located in the proximal colon might help explain why colonoscopy is less effective against right-sided compared to left-sided colorectal cancers and why interval cancers usually appear in the proximal colon. In fact, serrated polyps may cause up to one third of all sporadic colorectal cancers. In spite of this, the aetiology, incidence, prevalence and natural history of serrated polyps remains elusive. Endoscopists and pathologists must have a good understanding of serrated polyps in order to effectively diagnose, treat and follow up these lesions. This review focuses on the pathophysiology, types, work-up, treatment and follow-up of serrated polyps in the colon and rectum. PMID- 26284884 TI - [Not Available]. PMID- 26284885 TI - [Not Available]. PMID- 26284886 TI - [Hazardous supplements in athletes pill containers]. PMID- 26284887 TI - [The possibility of self-chosen end of life. Investigate living will]. PMID- 26284888 TI - Self-Healing Nanofiber-Reinforced Polymer Composites. 1. Tensile Testing and Recovery of Mechanical Properties. AB - The present work aims at development of self-healing materials capable of partially restoring their mechanical properties under the conditions of prolonged periodic loading and unloading, which is characteristic, for example, of aerospace applications. Composite materials used in these and many other applications frequently reveal multiple defects stemming from their original inhomogeneity, which facilitates microcracking and delamination at ply interfaces. Self-healing nanofiber mats may effectively prevent such damage without compromising material integrity. Two types of core-shell nanofibers were simultaneously electrospun onto the same substrate in order to form a mutually entangled mat. The first type of core-shell fibers consisted of resin monomer (dimethylsiloxane) within the core and polyacrylonitrile within the shell. The second type of core-shell nanofibers consisted of cure (dimethyl-methyl hydrogen siloxane) within the core and polyacrylonitrile within the shell. These mutually entangled nanofiber mats were used for tensile testing, and they were also encased in polydimethylsiloxane to form composites that were also subsequently subjected to tensile testing. During tensile tests, the nanofibers can be damaged in stretching up to the plastic regime of deformation. Then, the resin monomer and cure was released from the cores and the polydimethylsiloxane resin was polymerized, which might be expected to result in the self-healing properties of these materials. To reveal and evaluate the self-healing properties of the polyacrylonitrile-resin-cure nanofiber mats and their composites, the results were compared to the tensile test results of the monolithic polyacrylonitrile nanofiber mats or composites formed by encasing polyacrylonitrile nanofibers in a polydimethylsiloxane matrix. The latter do not possess self-healing properties, and indeed, do not recover their mechanical characteristics, in contrast to the polyacrylonitrile-resin-cure nanofiber mats and the composites reinforced by such mats. This is the first work, to the best of our knowledge, where self-healing nanofibers and composites based on them were developed, tested, and revealed restoration of mechanical properties (stiffness) in a 24 h rest period at room temperature. PMID- 26284889 TI - Eps15 homology domain containing protein of Plasmodium falciparum (PfEHD) associates with endocytosis and vesicular trafficking towards neutral lipid storage site. AB - The human malaria parasite, Plasmodium falciparum, takes up numerous host cytosolic components and exogenous nutrients through endocytosis during the intra erythrocytic stages. Eps15 homology domain-containing proteins (EHDs) are conserved NTPases, which are implicated in membrane remodeling and regulation of specific endocytic transport steps in eukaryotic cells. In the present study, we have characterized the dynamin-like C-terminal Eps15 homology domain containing protein of P. falciparum (PfEHD). Using a GFP-targeting approach, we studied localization and trafficking of PfEHD in the parasite. The PfEHD-GFP fusion protein was found to be a membrane bound protein that associates with vesicular network in the parasite. Time-lapse microscopy studies showed that these vesicles originate at parasite plasma membrane, migrate through the parasite cytosol and culminate into a large multi-vesicular like structure near the food-vacuole. Co staining of food vacuole membrane showed that the multi-vesicular structure is juxtaposed but outside the food vacuole. Labeling of parasites with neutral lipid specific dye, Nile Red, showed that this large structure is neutral lipid storage site in the parasites. Proteomic analysis identified endocytosis modulators as PfEHD associated proteins in the parasites. Treatment of parasites with endocytosis inhibitors obstructed the development of PfEHD-labeled vesicles and blocked their targeting to the lipid storage site. Overall, our data suggests that the PfEHD is involved in endocytosis and plays a role in the generation of endocytic vesicles at the parasite plasma membrane, that are subsequently targeted to the neutral lipid generation/storage site localized near the food vacuole. PMID- 26284890 TI - Development of an ultra-sensitive single molecule counting assay for the detection of interleukin-13 as a marker for asthmatic severity. AB - OBJECTIVE: Interleukin-13 (IL-13) has been difficult to quantify within human serum due to low abundance. Available assays have not been sensitive enough to detect IL-13 at the femtogram level. Thus, there are inconsistencies within the published literature as to IL-13 concentrations in normal or disease populations. To better understand IL-13 serum concentrations, a highly sensitive immunoassay was developed and used to determine concentrations from asthmatics with varying clinical severities. METHODS: A single molecule counting (SMC) method was used to analyze serum samples from a total of 145 individuals (60 severe asthma, 60 moderate asthma, 60 mild asthma and 23 healthy donors). RESULTS: IL-13 concentrations correlated with severity of asthma, with overlapping ranges. Mean IL-13 levels were highest in severe asthma. Mean IL-13 levels in moderate asthma population were second highest followed by mild asthma with the lowest IL-13 concentration. IL-13 concentrations in healthy donors were similar to the mild asthmatic population. The average concentrations of IL-13 in severe, moderate, mild and healthy donors were 1.286pg/mL, 0.672pg/mL, 0.508pg/mL and 0.155pg/mL respectively. CONCLUSION: Severe asthma patients have elevated levels of IL-13. PMID- 26284891 TI - Aggregate structure, morphology and the effect of aggregation mechanisms on viscosity at elevated protein concentrations. AB - Non-native aggregation is a common issue in a number of degenerative diseases and during manufacturing of protein-based therapeutics. There is a growing interest to monitor protein stability at intermediate to high protein concentrations, which are required for therapeutic dosing of subcutaneous injections. An understanding of the impact of protein structural changes and interactions on the protein aggregation mechanisms and resulting aggregate size and morphology may lead to improved strategies to reduce aggregation and solution viscosity. This report investigates non-native aggregation of a model protein, alpha chymotrypsinogen, under accelerated conditions at elevated protein concentrations. Far-UV circular dichroism and Raman scattering show structural changes during aggregation. Size exclusion chromatography and laser light scattering are used to monitor the progression of aggregate growth and monomer loss. Monomer loss is concomitant with increased beta-sheet structures as monomers are added to aggregates, which illustrate a transition from a native monomeric state to an aggregate state. Aggregates grow predominantly through monomer-addition, resulting in a semi-flexible polymer morphology. Analysis of aggregation growth kinetics shows that pH strongly affects the characteristic timescales for nucleation (taun) and growth (taug), while the initial protein concentration has only minor effects on taun or taug. Low-shear viscosity measurements follow a common scaling relationship between average aggregate molecular weight (Mw(agg)) and concentration (sigma), which is consistent with semi-dilute polymer-solution theory. The results establish a link between aggregate growth mechanisms, which couple Mw(agg) and sigma, to increases in solution viscosity even at these intermediate protein concentrations (less than 3w/v %). PMID- 26284892 TI - Efficacy of Different Types of Mobilization Techniques in Patients With Primary Adhesive Capsulitis of the Shoulder: A Systematic Review. AB - OBJECTIVE: To systematically review the literature for efficacy of isolated articular mobilization techniques in patients with primary adhesive capsulitis (AC) of the shoulder. DATA SOURCES: PubMed and Web of Science were searched for relevant studies published before November 2014. Additional references were identified by manual screening of the reference lists. STUDY SELECTION: All English language randomized controlled trials evaluating the efficacy of mobilization techniques on range of motion (ROM) and pain in adult patients with primary AC of the shoulder were included in this systematic review. Twelve randomized controlled trials involving 810 patients were included. DATA EXTRACTION: Two reviewers independently screened the articles, scored methodologic quality, and extracted data for analysis. The review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. All studies were assessed in duplicate for risk of bias using the Physiotherapy Evidence Database Scale for randomized controlled trials. DATA SYNTHESIS: The efficacy of 7 different types of mobilization techniques was evaluated. Angular mobilization (n=2), Cyriax approach (n=1), and Maitland technique (n=6) showed improvement in pain score and ROM. With respect to translational mobilizations (n=1), posterior glides are preferred to restore external rotation. Spine mobilizations combined with glenohumeral stretching and both angular and translational mobilization (n=1) had a superior effect on active ROM compared with sham ultrasound. High-intensity mobilization (n=1) showed less improvement in the Constant Murley Score than a neglect group. Finally, positive long-term effects of the Mulligan technique (n=1) were found on both pain and ROM. CONCLUSIONS: Overall, mobilization techniques have beneficial effects in patients with primary AC of the shoulder. Because of preliminary evidence for many mobilization techniques, the Maitland technique and combined mobilizations seem recommended at the moment. PMID- 26284894 TI - Synthesis and Chiroptical Properties of Double-Helical (M)- and (P)-o Oligophenylenes. AB - All of the M and P isomers of optically pure oligophenylenes with 6, 8, 10, and 12 phenyl rings were synthesized and fully characterized. The Suzuki cross coupling reaction has been revealed to be a viable strategy in the syntheses of tetraphenylene derivatives, which, together with the copper-mediated oxidative cross-coupling reaction, were employed in the quest for the oligophenylenes. X ray diffraction analysis in combination with specific rotation and circular dichroism spectroscopy unambiguously identified the unique covalent double helical frameworks of these oligophenylene molecules. PMID- 26284893 TI - The interneuron energy hypothesis: Implications for brain disease. AB - Fast-spiking, inhibitory interneurons - prototype is the parvalbumin-positive (PV+) basket cell - generate action potentials at high frequency and synchronize the activity of numerous excitatory principal neurons, such as pyramidal cells, during fast network oscillations by rhythmic inhibition. For this purpose, fast spiking, PV+ interneurons have unique electrophysiological characteristics regarding action potential kinetics and ion conductances, which are associated with high energy expenditure. This is reflected in the neural ultrastructure by enrichment with mitochondria and cytochrome c oxidase, indicating the dependence on oxidative phosphorylation for adenosine-5'-triphosphate (ATP) generation. The high energy expenditure is most likely required for membrane ion transport in dendrites and the extensive axon arbor as well as for presynaptic release of neurotransmitter, gamma-aminobutyric acid (GABA). Fast-spiking, PV+ interneurons are central for the emergence of gamma oscillations (30-100Hz) that provide a fundamental mechanism of complex information processing during sensory perception, motor behavior and memory formation in networks of the hippocampus and the neocortex. Conversely, shortage in glucose and oxygen supply (metabolic stress) and/or excessive formation of reactive oxygen and nitrogen species (oxidative stress) may render these interneurons to be a vulnerable target. Dysfunction in fast-spiking, PV+ interneurons might set a low threshold for impairment of fast network oscillations and thus higher brain functions. This pathophysiological mechanism might be highly relevant for cerebral aging as well as various acute and chronic brain diseases, such as stroke, vascular cognitive impairment, epilepsy, Alzheimer's disease and schizophrenia. PMID- 26284895 TI - Controls and forecasts of nitrate yields in forested watersheds: A view over mainland Portugal. AB - A study on nitrate yields was conducted in forested watersheds of mainland Portugal. The prime goal was to rank parameters in descending order of their contribution to the export of nitrate towards streams and lakes. To attain the goal, variables like soil loss, rainfall intensity, topography, soil type, forest composition and environmental disturbances such as hardwood harvesting or wildfires were organized in a conceptual yield model. Because some parameters were potentially collinear, a robust multivariate statistical technique was selected to execute the conceptual model and perform the aforementioned ranking, namely Partial Least Squares (PLS) regression. This technique was tested with a sample of 60 forested watersheds (>70% of forest occupation), being subject to a double-validation process to ensure prediction capability. According to final regression coefficients, soil erosion seems to regulate nitrate distribution across the basins, because soil loss and type, rainfall intensity and topography explained around 60% of nitrate yield variance. The major importance of erosion is followed by a moderate role of biochemical processes such as nitrification or nutrient uptake, which accounted for approximately 15% of nitrate yield variance. In this case, deciduous forests and scrubland seem to behave as net sinks of nitrate while coniferous and mixed forests seem to act dually, as net sources or sinks. The least important parameters are the environmental disturbances, explaining no more than 5% of nitrate yield variance. The results of PLS regression were coupled in a scenario analysis with measures designed to protect soil from erosion and surface water from eutrophication. These interventions are to be implemented until 2045, according to regional plans of forest management. Considering the key role of erosion in explaining nitrate dynamics across the catchments, it was not surprising to verify that soil protection measures may reduce nitrate yields by some 35% of their current values. PMID- 26284896 TI - Dynamic silver speciation as studied with fluorous-phase ion-selective electrodes: Effect of natural organic matter on the toxicity and speciation of silver. AB - The widespread application of silver in consumer products and the resulting contamination of natural environments with silver raise questions about the toxicity of Ag(+) in the ecosystem. Natural organic matter, NOM, which is abundant in water supplies, soil, and sediments, can form stable complexes with Ag(+), altering its bioavailability and toxicity. Herein, the extent and kinetics of Ag(+) binding to NOM, matrix effects on Ag(+) binding to NOM, and the effect of NOM on Ag(+) toxicity to Shewanella oneidensis MR-1 (assessed by the BacLight viability assay) were quantitatively studied with fluorous-phase Ag(+) ion selective electrodes (ISEs). Our findings show fast kinetics of Ag(+) and NOM binding, weak Ag(+) binding for Suwannee River humic acid, fulvic acid, and aquatic NOM, and stronger Ag(+) binding for Pony Lake fulvic acid and Pahokee Peat humic acid. We quantified the effects of matrix components and pH on Ag(+) binding to NOM, showing that the extent of binding greatly depends on the environmental conditions. The effect of NOM on the toxicity of Ag(+) does not correlate with the extent of Ag(+) binding to NOM, and other forms of silver, such as Ag(+) reduced by NOM, are critical for understanding the effect of NOM on Ag(+) toxicity. This work also shows that fluorous-phase Ag(+) ISEs are effective tools for studying Ag(+) binding to NOM because they can be used in a time resolved manner to monitor the activity of Ag(+) in situ with high selectivity and without the need for extensive sample preparation. PMID- 26284897 TI - Postural Steadiness and Ankle Force Variability in Peripheral Neuropathy. AB - INTRODUCTION: The purpose was to determine the effect of peripheral neuropathy (PN) on motor output variability for ankle muscles of older adults, and the relation between ankle motor variability and postural stability in PN patients. METHODS: Older adults with (O-PN) and without PN (O), and young adults (Y) underwent assessment of standing postural stability and ankle muscle force steadiness. RESULTS: O-PN displayed impaired ankle muscle force control and postural stability compared with O and Y groups. For O-PN, the amplitude of plantarflexor force fluctuations was moderately correlated with postural stability under no-vision conditions (r = .54, p = .01). DISCUSSION: The correlation of variations in ankle force with postural stability in PN suggests a contribution of ankle muscle dyscontrol to the postural instability that impacts physical function for older adults with PN. PMID- 26284898 TI - Protonation Dynamics and Hydrogen Bonding in Aqueous Sulfuric Acid. AB - Hydration of sulfuric acid plays a key role in new-particle formation in the atmosphere. It has been recently proposed that proton dynamics is crucial in the stabilization of these clusters. One key question is how water molecules mediate proton transfer from sulfuric acid, and hence how the deprotonation state of the acid molecule behaves as a function concentration. We address the proton transfer in aqueous sulfuric acid with O K edge and S L edge core-excitation spectra recorded using inelastic X-ray scattering and with ab initio molecular dynamics simulations in the concentration range of 0-18.0 M. Throughout this range, we quantify the acid-water interaction with atomic resolution. Our simulations show that the number of donated hydrogen bonds per Owater increases from 1.9 to 2.5 when concentration increases from 0 to 18.0 M, in agreement with a rapid disappearance of the pre-edge feature in the O K edge spectrum. The simulations also suggest that for 1.5 M sulfuric acid SO4(2-) is most abundant and that its concentration falls monotonously with increasing concentration. Moreover, the fraction of HSO4(-) peaks at ~12 M. PMID- 26284899 TI - An Effective Electrical Throughput from PANI Supplement ZnS Nanorods and PDMS Based Flexible Piezoelectric Nanogenerator for Power up Portable Electronic Devices: An Alternative of MWCNT Filler. AB - We demonstrate the requirement of electrical poling can be avoided in flexible piezoelectric nanogenerators (FPNGs) made of low-temperature hydrothermally grown wurtzite zinc sulfide nanorods (ZnS-NRs) blended with polydimethylsiloxane (PDMS). It has been found that conductive fillers, such as polyaniline (PANI) and multiwall carbon nanotubes (MWCNTs), can subsequently improve the overall performance of FPNG. A large electrical throughput (open circuit voltage ~35 V with power density ~2.43 MUW/cm(3)) from PANI supplement added nanogenerator (PZP FPNG) indicates that it is an effective means to replace the MWCNTs filler. The time constant (tau) estimated from the transient response of the capacitor charging curves signifying that the FPNGs are very much capable to charge the capacitors in very short time span (e.g., 3 V is accomplished in 50 s) and thus expected to be perfectly suitable in portable, wearable and flexible electronics devices. We demonstrate that FPNG can instantly lit up several commercial Light Emitting Diodes (LEDs) (15 red, 25 green, and 55 blue, individually) and power up several portable electronic gadgets, for example, wrist watch, calculator, and LCD screen. Thus, a realization of potential use of PANI in low-temperature synthesized ZnS-NRs comprising piezoelectric based nanogenerator fabrication is experimentally verified so as to acquire a potential impact in sustainable energy applications. Beside this, wireless piezoelectric signal detection possibility is also worked out where a concept of self-powered smart sensor is introduced. PMID- 26284900 TI - In Situ Formation of Metal Oxide Nanocrystals Embedded in Laser-Induced Graphene. AB - Hybrid materials incorporating the advantages of graphene and nanoparticles have been widely studied. Here we develop an improved cost-effective approach for preparation of porous graphene embedded with various types of nanoparticles. Direct laser scribing on metal-complex-containing polyimide film leads to in situ formation of nanoparticles embedded in porous graphene. These materials are highly active in electrochemical oxygen reduction reactions, converting O2 into OH(-), with a low metal loading of less than 1 at. %. In addition, the nanoparticles can vary from metal oxide to metal dichalcogenides through lateral doping, making the composite active in other electrocatalytic reactions such as hydrogen evolution. PMID- 26284901 TI - Mediastinal Granulomatous Inflammation and Overall Survival in Patients with a History of Malignancy. AB - RATIONALE: Investigators have postulated that mediastinal granulomatous inflammation is associated with prolonged overall survival in patients with cancer. OBJECTIVES: We sought to determine whether mediastinal granulomatous inflammation affects overall survival in patients with a history of treated cancer. METHODS: Patients with a history of treated cancer who underwent endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) for evaluation of mediastinal or hilar lymphadenopathy were grouped based on whether they had mediastinal granulomatous inflammation or benign mediastinal lymphadenopathy without granulomas. Overall survival from the date of EBUS-TBNA to cancer-related death or to last follow-up in patient groups was compared. MEASUREMENTS AND MAIN RESULTS: We reviewed the records of 106 patients (44 with mediastinal granulomatous inflammation and 62 with benign mediastinal lymphadenopathy). The 3-year survival rate was 90% overall and 93 and 88% in patients with mediastinal granulomatous inflammation and benign mediastinal lymphadenopathy, respectively (P=0.40). After multivariate adjustment, whether patients had mediastinal granulomatous inflammation or benign mediastinal lymphadenopathy did not significantly affect the risk of cancer death (mediastinal granulomatous inflammation to benign mediastinal lymphadenopathy hazard ratio, 1.27; P=0.76). CONCLUSIONS: These results suggest that patients who develop mediastinal granulomatous inflammation after cancer treatment do not have an increased overall survival when compared with patients who develop benign mediastinal lymphadenopathy. EBUS-TBNA is warranted for patients with treated cancer who develop mediastinal and/or hilar lymphadenopathy to avoid erroneous upstaging or misdiagnosis of cancer recurrence that would lead to suboptimal management. PMID- 26284902 TI - Global trends of municipal solid waste research from 1997 to 2014 using bibliometric analysis. AB - This study uses a bibliometric approach to identify global trends related to the municipal solid waste (MSW). It applies related literature in the Science Citation Index Expanded (SCI-EXPANDED), Social Sciences Citation Index (SSCI), Conference Proceedings Citation Index - Science (CPCI-S) and Conference Proceedings Citation Index - Social Science & Humanities (CPCI-SSH), retrieved from the ISI Web of Science. The data used covers the period from 1997 to 2014. Analyzed aspects included document type, and publication output as well as distribution of journals, subject category, countries, institutions, title-words, author keywords, and keywords plus. An evaluating indicator, citation score, was applied to characterize the MSW publications. The research outputs of MSW had steadily increased in the field of energy fuels, engineering chemical and biotechnology applied microbiology, especially environmental sciences and engineering environmental. The predominance of Chinese institutions in terms of article count and a predominance of industrialized countries' institutions in terms of citation score were compared. Finally, author keywords, words in title, and keywords plus were analyzed to provide research emphasis, with the developing trends and recent hotspots provided. IMPLICATIONS: A systematic overview of scientific literature dealing with municipal solid waste (MSW) is provided by a bibliometric analysis. The analysis of author keywords helps in drawing the research trends in a special perspective. Research studies on food waste, life cycle assessment (LCA), and renewable energy tend to be a new research focus in the area of MSW. The conclusions could provide a reference to the decision making and policy of MSW management for the government to some extent. PMID- 26284903 TI - Combination of Calcium Hydroxyapatite Antibiotic Carrier with Cement Spacers in Peri-Prosthetic Knee Infections. AB - BACKGROUND: Forty-six patients (38 females and 8 males) with infected knee arthroplasties were included in this study. In 31 patients (group A) an antibiotic-impregnated articulating spacer was used, whereas in 15 patients (group B) a combination of spacer and antibiotic carrier was used. METHODS: All patients were reviewed weekly with laboratory examinations (white blood cell count [WBC], erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]) prior to re-implantation. At a mean follow-up of 36 mo (range, 8-60 mo) no patient was lost to follow-up or had died. RESULTS: White blood cell count and ESR showed no differences at any time interval. C-reactive protein values had a statistically significant difference between the two groups after the second week (third week p = 0.042) and group B had significantly lower CRP values at every checkpoint thereafter. The re-infection rate was 16.12% in group A and 6.6% in group B (p = 0.192). PMID- 26284904 TI - The mRNA expression of soluble urokinase plasminogen activator surface receptor in human adipose tissue is positively correlated with body mass index. AB - suPLAUR is the transcript variant that encodes the soluble form of the urokinase plasminogen activator surface receptor (suPLAUR). This soluble protein has been shown to enhance leukocyte migration and adhesion, and its circulatory level is increased in inflammatory states. In this pilot study, we used RNA-Seq to examine the splicing pattern of PLAUR in omental adipose tissues from obese and lean individuals. Of the three transcript variants of the PLAUR gene, only the proportion of suPLAUR (transcript variant 2) increases in obesity. After removing the effects of gender and age, the expression of suPLAUR is positively correlated with body mass index. This observation was validated using RT-qPCR with an independent cohort of samples. Additionally, in our RNA-Seq differential expression analysis, we also observed, in obese adipose tissues, an up-regulation of genes encoding other proteins involved in the process of chemotaxis and leukocyte adhesion; of particular interest is the integrin beta 2 (ITGB2) that is known to interact with suPLAUR in leukocyte adhesion. These findings suggest an important role for suPLAUR in the recruitment of immune cells to obese adipose tissue, in the pathogenesis of obesity. PMID- 26284905 TI - The effect of SIRT1 gene polymorphisms on ambulatory blood pressure of hypertensive patients in the Kazakh population. AB - OBJECTIVE: To investigate the effect of silent information regulator 1 (SIRT1) gene polymorphisms on ambulatory blood pressure in hypertensive patients. METHODS: Three hundred forty hypertensive patients were recruited from January 2013 to January 2015. SIRT1 Tag single-nucleotide polymorphisms (SNPs; rs2273773, rs4746720, and rs7896005) were genotyped using a PCR-direct sequencing method, and the association between the SIRT1 gene SNPs and ambulatory blood pressure was analyzed. RESULTS: After adjusting for confounding factors, patients with the rs2273773/CT+CC genotypes had lower 24-h systolic and diastolic blood pressures; there were no associations between rs4746720 and rs7896005 genotypes and blood pressure. CONCLUSION: The SIRT1 gene polymorphism (rs2273773) is significantly associated with ambulatory blood pressure level in Han Chinese patients with hypertension. PMID- 26284906 TI - Cordyceps militaris Enhances Cell-Mediated Immunity in Healthy Korean Men. AB - Cordyceps militaris is a mushroom traditionally used for diverse pharmaceutical purposes in East Asia, including China, and has been found to be effective for enhancing immunity through various types of animal testing. The aim of this study is to determine the efficacy of C. militaris for enhancing cell-mediated immunity and its safety in healthy male adults. Healthy male adults were divided into the experimental group (n = 39), given 1.5 g/day of ethanol treated C. militaris in capsules, and the control group (n = 40), given the same number of identical placebo capsules filled with microcrystalline cellulose and lactose for 4 weeks from February 13 to March 14, 2012; the natural killer (NK) cell activity, lymphocyte proliferation index (PI), and T-helper cell 1 (Th1) cytokine cluster (interferon [IFN]-gamma, interleukin [IL]-12, IL-2, and tumor necrosis factor [TNF]-alpha) were measured, along with stability test, at weeks 0, 2, and 4. The C. militaris group showed a statistically significant greater increase in NK200 (P = .0010), lymphocyte PI (P <= .0001), IL-2 (P = .0096), and IFN-gamma (P = .0126), compared with the basal level, than the placebo group. There was no statistically significant adverse reaction. C. militaris enhanced the NK cell activity and lymphocyte proliferation and partially increased Th1 cytokine secretion. Therefore, C. militaris is safe and effective for enhancing cell mediated immunity of healthy male adults. PMID- 26284907 TI - A Large Repetitive RTX-Like Protein Mediates Water-Soaked Lesion Development, Leakage of Plant Cell Content and Host Colonization in the Pantoea stewartii subsp. stewartii Pathosystem. AB - Pantoea stewartii subsp. stewartii is the etiological agent of Stewart's wilt and is a serious bacterial pathogen affecting sweet corn. During the leaf blight phase, P. stewartii colonizes the leaf apoplast and causes a characteristic water soaked lesion. The Hrp type III secretion system has been implicated in the water soaking phenotype, and the goal of this study was to investigate other potential factors that contribute to the plant cellular disruption associated with these lesions. The P. stewartii genome contains a gene encoding a large repetitive RTX toxin, designated rtx2. RTX toxins comprise a large family of pore-forming proteins, which are widely distributed among gram-negative bacteria. These cytotoxins usually lyse their target host cells and cause significant tissue damage as a consequence. We hypothesized that this RTX-like toxin plays a role in the water-soaking phase of infection due to its predicted cytolytic properties. Based on the data reported here, we conclude that RTX2 contributes significantly to the development of water-soaked lesions and leakage of plant cellular contents and is an important pathogenicity factor for P. stewartii. PMID- 26284908 TI - Genome-Wide Association of Rice Blast Disease Resistance and Yield-Related Components of Rice. AB - Robust disease resistance may require an expenditure of energy that may limit crop yield potential. In the present study, a subset of a United States Department of Agriculture rice core collection consisting of 151 accessions was selected using a major blast resistance (R) gene, Pi-ta, marker and was genotyped with 156 simple sequence repeat (SSR) markers. Disease reactions to Magnaporthe oryzae, the causal agent of rice blast disease, were evaluated under greenhouse and field conditions, and heading date, plant height, paddy and brown seed weight in two field environments were analyzed, using an association mapping approach. A total of 21 SSR markers distributed among rice chromosomes 2 to 12 were associated with blast resistance, and 16 SSR markers were associated with seed weight, heading date, and plant height. Most noticeably, shorter plants were significantly correlated with resistance to blast, rice genomes with Pi-ta were associated with lighter seed weights, and the susceptible alleles of RM171 and RM6544 were associated with heavier seed weight. These findings unraveled a complex relationship between disease resistance and yield-related components. PMID- 26284910 TI - Exploring the Health Belief Model and first-year students' responses to HIV/AIDS and VCT at a South African university. AB - The Health Belief Model (HBM) is a psychosocial framework that attempts to explain health behaviour. It is determined by an individual's personal beliefs or perceptions about a disease and the options available to decrease its occurrence. In the context of sexual risk behaviours, literature reveals that knowledge about HIV/AIDS and Voluntary Counselling and Testing (VCT) are key strategies in the management and prevention of HIV. This study was conducted in 2011, the same year the First Things First campaign was implemented in universities across South Africa to maximise opportunities for HIV testing among youth. It aimed to identify first-year students' responses to HIV/AIDS and VCT at the University of the Witwatersrand (WITS). The mixed research methods consisted of self administered structured questionnaires with a sample population of 195 first-year students and 2 in-depth interviews with experts in the field of HIV/AIDS. Descriptive statistical analyses (frequencies and cross-tabulations) and thematic content analysis was carried out. The findings indicate that students are willing to know their status. The positive influence of peers is a motivation for those accessing VCT. However, some students do not access VCT due to personal fears while other students do not access VCT because of their low individual risk perception for HIV due to sexual abstinence. It concludes that university students' self-efficacy and cues to action might bring about a positive change in the future of the epidemic within a university context. PMID- 26284909 TI - Unusual cutaneous features associated with a heterozygous gain-of-function mutation in IFIH1: overlap between Aicardi-Goutieres and Singleton-Merten syndromes. AB - Cutaneous lesions described as chilblain lupus occur in the context of familial chilblain lupus or Aicardi-Goutieres syndrome. To date, seven genes related to Aicardi-Goutieres syndrome have been described. The most recently described encodes the cytosolic double-stranded RNA receptor IFIH1 (also known as MDA5), a key component of the antiviral type I interferon-mediated innate immune response. Enhanced type I interferon signalling secondary to gain-of-function mutations in IFIH1 can result in a range of neuroinflammatory phenotypes including classical Aicardi-Goutieres syndrome. It is of note that none of the patients with a neurological phenotype so far described with mutations in this gene was reported to demonstrate cutaneous involvement. We present a family segregating a heterozygous pathogenic mutation in IFIH1 showing dermatological involvement as a prominent feature, variably associated with neurological disturbance and premature tooth loss. All three affected individuals exhibited increased expression of interferon-stimulated genes in whole blood, and the mutant protein resulted in enhanced interferon signalling in vitro, both in the basal state and following ligand stimulation. Our results further extend the phenotypic spectrum associated with mutations in IFIH1, indicating that the disease can be confined predominantly to the skin, while also highlighting phenotypic overlap with both Aicardi-Goutieres syndrome and Singleton-Merten syndrome. PMID- 26284911 TI - Absorbance amplification using chromophore-nanoplasmon coupling for ultrasensitive protein quantification. AB - A plasmonic nanoscale Lycurgus cup array (nanoLCA), via near-field interaction with chromophores in commercial colorimetric biochemical assays, can drastically enhance assay sensitivity by over 2 orders of magnitude. A 96-microwell plate modified by placing the plasmonic nanoLCA on the well-bottom was used with the commercial Bradford protein quantification assay. Plasmons on the nanoLCA serve as an energy donor to matched resonance chromophores, and the near-field plasmonic energy coupling effect results in an increase in absorbance value at the plasmonic resonance wavelength. Even with a 5.1-fold reduced sample volume, a limit of detection enhancement factor of 200 is accomplished using the nanoLCA compared to using the conventional Bradford assay without plasmon aid. The nanoLCA-microplate sensing platform is readily scalable to 384- or 1536-microwell plates, which further reduces the sensing volume and boosts detection throughput with the enhanced sensitivity. PMID- 26284912 TI - Precision Nursing: New Era of Cancer Care. PMID- 26284913 TI - Survivorship Care Provision for Patients With Hematologic Malignancies: The Quest for Quality Evidence. PMID- 26284914 TI - Silk Reconstitution Disrupts Fibroin Self-Assembly. AB - Using atomic force microscopy, we present the first molecular-scale comparison of two of the most important silk dopes, native (NSF) and reconstituted (RSF) silkworm fibroin. We found that both systems depended on shear to show self assembly. Significant differences in the nature of self-assembly between NSF and RSF were shown. In the highest studied concentration of 1000 mg/L, NSF exhibited assembly into 20-30 nm-wide nanofibrils closely resembling the surface structures found in natural silk fibers. RSF, in contrast, showed no self-assembly whatsoever at the same concentration, which suggests that the reconstitution process significantly disrupts silk's inherent self-assembly capability. At lower concentrations, both RSF and NSF formed fibrils under shear, apparently denatured by the substrate. Using image analysis, we quantified the properties of these self-assembled fibrils as a function of concentration and found low-concentration fibrils of NSF to form larger continuous structures than those of RSF, further supporting NSF's superior self-assembly capabilities. PMID- 26284915 TI - A carbon coated NASICON structure material embedded in porous carbon enabling superior sodium storage performance: NaTi2(PO4)3 as an example. AB - Sodium super ion conductor (NASICON) type structure materials (e.g. Na3V2(PO4)3, NaTi2(PO4)3) have been considered as promising electrode materials for sodium-ion batteries (NIBs). However, the inherent poor electronic conductivity of the NASICON type structure materials owing to their poor electronic conductivity of phosphates leads to poor cyclability and rate capability. Here, we develop a general strategy to achieve high rate capability and long cycle life by preparing "double carbon coating" NASICON NaTi2(PO4)3 using a soft-chemical method. The obtained carbon-coated NaTi2(PO4)3 within the porous carbon matrix (denoted as NTP@C@PC) imparts a reversible capability of 103 mA h g(-1) at 5 C after 5000 cycles and a rate capability of 64 mA h g(-1) at 50 C for sodium storage. The high capacity, stable cyclability and excellent rate capability of the NTP@C@PC are attributed to the advantages of the special structure: the fast Na(+)/e(-) transfer in the nanocomposites, large surface area and mesoporous nature of the 3D porous carbon matrix that facilitate the electrolyte to soak in, an intimate interaction between the particles and the carbon matrix. In addition, the 3D porous carbon matrix could effectively accommodate the volume variation during a repeated sodiation/desodiation process. PMID- 26284916 TI - Summer Precipitation Predicts Spatial Distributions of Semiaquatic Mammals. AB - Climate change is predicted to increase the frequency of droughts and intensity of seasonal precipitation in many regions. Semiaquatic mammals should be vulnerable to this increased variability in precipitation, especially in human modified landscapes where dispersal to suitable habitat or temporary refugia may be limited. Using six years of presence-absence data (2007-2012) spanning years of record-breaking drought and flood conditions, we evaluated regional occupancy dynamics of American mink (Neovison vison) and muskrats (Ondatra zibethicus) in a highly altered agroecosystem in Illinois, USA. We used noninvasive sign surveys and a multiseason occupancy modeling approach to estimate annual occupancy rates for both species and related these rates to summer precipitation. We also tracked radiomarked individuals to assess mortality risk for both species when moving in terrestrial areas. Annual model-averaged estimates of occupancy for mink and muskrat were correlated positively to summer precipitation. Mink and muskrats were widespread during a year (2008) with above-average precipitation. However, estimates of site occupancy declined substantially for mink (0.56) and especially muskrats (0.09) during the severe drought of 2012. Mink are generalist predators that probably use terrestrial habitat during droughts. However, mink had substantially greater risk of mortality away from streams. In comparison, muskrats are more restricted to aquatic habitats and likely suffered high mortality during the drought. Our patterns are striking, but a more mechanistic understanding is needed of how semiaquatic species in human-modified ecosystems will respond ecologically in situ to extreme weather events predicted by climate change models. PMID- 26284917 TI - Innate Immunity and the Inter-exposure Interval Determine the Dynamics of Secondary Influenza Virus Infection and Explain Observed Viral Hierarchies. AB - Influenza is an infectious disease that primarily attacks the respiratory system. Innate immunity provides both a very early defense to influenza virus invasion and an effective control of viral growth. Previous modelling studies of virus innate immune response interactions have focused on infection with a single virus and, while improving our understanding of viral and immune dynamics, have been unable to effectively evaluate the relative feasibility of different hypothesised mechanisms of antiviral immunity. In recent experiments, we have applied consecutive exposures to different virus strains in a ferret model, and demonstrated that viruses differed in their ability to induce a state of temporary immunity or viral interference capable of modifying the infection kinetics of the subsequent exposure. These results imply that virus-induced early immune responses may be responsible for the observed viral hierarchy. Here we introduce and analyse a family of within-host models of re-infection viral kinetics which allow for different viruses to stimulate the innate immune response to different degrees. The proposed models differ in their hypothesised mechanisms of action of the non-specific innate immune response. We compare these alternative models in terms of their abilities to reproduce the re-exposure data. Our results show that 1) a model with viral control mediated solely by a virus resistant state, as commonly considered in the literature, is not able to reproduce the observed viral hierarchy; 2) the synchronised and desynchronised behaviour of consecutive virus infections is highly dependent upon the interval between primary virus and challenge virus exposures and is consistent with virus dependent stimulation of the innate immune response. Our study provides the first mechanistic explanation for the recently observed influenza viral hierarchies and demonstrates the importance of understanding the host response to multi-strain viral infections. Re-exposure experiments provide a new paradigm in which to study the immune response to influenza and its role in viral control. PMID- 26284918 TI - A Comparison of the Effects of the GLP-1 Analogue Liraglutide and Insulin Glargine on Endothelial Function and Metabolic Parameters: A Randomized, Controlled Trial Sapporo Athero-Incretin Study 2 (SAIS2). AB - OBJECTIVES: GLP-1 improves hyperglycemia, and it has been reported to have favorable effects on atherosclerosis. However, it has not been fully elucidated whether GLP-1 is able to improve endothelial function in patients with type 2 diabetes. Therefore, we investigated the efficacy of the GLP-1 analogue, liraglutide on endothelial function and glycemic metabolism compared with insulin glargine therapy. MATERIALS AND METHODS: In this multicenter, prospective randomized parallel-group comparison study, 31 diabetic outpatients (aged 60.3 +/ 10.3 years with HbA1c levels of 8.6 +/- 0.8%) with current metformin and/or sulfonylurea treatment were enrolled and randomly assigned to receive liraglutide or glargine therapy once daily for 14 weeks. Flow mediated dilation (FMD), a comprehensive panel of hemodynamic parameters (Task Force Monitor), and serum metabolic markers were assessed before and after the treatment period. RESULTS: A greater reduction (worsening) in %FMD was observed in the glargine group, although this change was not statistically different from the liraglutide group (liraglutide; 5.7 to 5.4%, glargine 6.7 to 5.7%). The augmentation index, C peptide index, derivatives of reactive oxygen metabolites and BMI were significantly improved in the liraglutide group. Central systolic blood pressure and NT-proBNP also tended to be improved in the liraglutide-treated group, while improvements in HbA1c levels were similar between groups. Cardiac index, blood pressure and most other metabolic parameters were not different. CONCLUSIONS: Regardless of glycemic improvement, early liraglutide therapy did not affect endothelial function but may provide favorable effects on beta-cell function and cardioprotection in type 2 diabetics without advanced atherosclerosis. TRIAL REGISTRATION: UMIN Clinical Trials Registry System as trial ID UMIN000005331. PMID- 26284919 TI - Matrix Metalloproteinase 9 Exerts Antiviral Activity against Respiratory Syncytial Virus. AB - Increased lung levels of matrix metalloproteinase 9 (MMP9) are frequently observed during respiratory syncytial virus (RSV) infection and elevated MMP9 concentrations are associated with severe disease. However little is known of the functional role of MMP9 during lung infection with RSV. To determine whether MMP9 exerted direct antiviral potential, active MMP9 was incubated with RSV, which showed that MMP9 directly prevented RSV infectivity to airway epithelial cells. Using knockout mice the effect of the loss of Mmp9 expression was examined during RSV infection to demonstrate MMP9's role in viral clearance and disease progression. Seven days following RSV infection, Mmp9-/- mice displayed substantial weight loss, increased RSV-induced airway hyperresponsiveness (AHR) and reduced clearance of RSV from the lungs compared to wild type mice. Although total bronchoalveolar lavage fluid (BALF) cell counts were similar in both groups, neutrophil recruitment to the lungs during RSV infection was significantly reduced in Mmp9-/- mice. Reduced neutrophil recruitment coincided with diminished RANTES, IL-1beta, SCF, G-CSF expression and p38 phosphorylation. Induction of p38 signaling was required for RANTES and G-CSF expression during RSV infection in airway epithelial cells. Therefore, MMP9 in RSV lung infection significantly enhances neutrophil recruitment, cytokine production and viral clearance while reducing AHR. PMID- 26284921 TI - Effects of oxygen impurities and nitrogen vacancies on the surface properties of the Ta3N5 photocatalyst: a DFT study. AB - Surface defects and impurities play important roles in the photocatalytic performance of semiconductors. In this study, DFT calculations are performed to investigate the effects of oxygen impurities and nitrogen vacancies on the surface stability and electronic structures of Ta3N5(100), (010) and (001) low index surfaces. The results show that, for each surface, the oxygen impurities and nitrogen vacancies are beneficial and harmful, respectively, to the surface stability of Ta3N5. The oxygen impurities and nitrogen vacancies have mainly two effects on the surface electronic structures of Ta3N5. One is saturating surface states on the clean surface, and the other is inducing the downshift of conduction band minimum. In addition, the Ta3N5(100) surface with oxygen impurities is expected to have the strongest reduction ability in practice, providing useful guidance for further investigations of Ta3N5 in the photocatalytic hydrogen evolution. PMID- 26284920 TI - Multidrug-Resistant Tuberculosis in Patients with Chronic Obstructive Pulmonary Disease in China. AB - BACKGROUND: Relatively little is known about the specific relationship and impact from chronic obstructive pulmonary disease (COPD) on multidrug-resistant tuberculsosis (MDR-TB). METHODS: We conducted a retrospective study included patients aged >=40 years with a confirmed pulmonary TB at three tertiary hospitals (Shandong, China) between January 2011 and October 2014. Univariable and multivariable analyses were performed to identify the relationship of MDR-TB and COPD. RESULTS: A total of 2164 patients aged >= 40 years with available results of drug susceptibility test (DST) and medical records were screened for this study: 268 patients with discharge diagnosis of COPD and 1896 patients without COPD. Overall, 14.2% of patients with COPD and 8.5% patients without COPD were MDR-TB. The rate of MDR-TB were significantly higher in patients with COPD (P<0.05). Migrant (odds ratios (OR) 1.32, 95% confidence interval (CI) 1.02 1.72), previous anti-TB treatment (OR 4.58, 95% CI 1.69-12.42), cavity (OR 2.33, 95% CI 1.14-4.75), and GOLD stage (OR 1.86, 95% CI 1.01-2.93) were the independent predictors for MDR-TB among patients with COPD. CONCLUSIONS: MDR-TB occurs more frequently in patients with underlying COPD, especially those with being migrant, previous anti-TB therapy, cavity and severe airway obstruction. PMID- 26284923 TI - Parallel Key Frame Extraction for Surveillance Video Service in a Smart City. AB - Surveillance video service (SVS) is one of the most important services provided in a smart city. It is very important for the utilization of SVS to provide design efficient surveillance video analysis techniques. Key frame extraction is a simple yet effective technique to achieve this goal. In surveillance video applications, key frames are typically used to summarize important video content. It is very important and essential to extract key frames accurately and efficiently. A novel approach is proposed to extract key frames from traffic surveillance videos based on GPU (graphics processing units) to ensure high efficiency and accuracy. For the determination of key frames, motion is a more salient feature in presenting actions or events, especially in surveillance videos. The motion feature is extracted in GPU to reduce running time. It is also smoothed to reduce noise, and the frames with local maxima of motion information are selected as the final key frames. The experimental results show that this approach can extract key frames more accurately and efficiently compared with several other methods. PMID- 26284922 TI - Fabrication of Acrylonitrile-Butadiene-Styrene Nanostructures with Anodic Alumina Oxide Templates, Characterization and Biofilm Development Test for Staphylococcus epidermidis. AB - Medical devices can be contaminated by microbial biofilm which causes nosocomial infections. One of the strategies for the prevention of such microbial adhesion is to modify the biomaterials by creating micro or nanofeatures on their surface. This study aimed (1) to nanostructure acrylonitrile-butadiene-styrene (ABS), a polymer composing connectors in perfusion devices, using Anodic Alumina Oxide templates, and to control the reproducibility of this process; (2) to characterize the physico-chemical properties of the nanostructured surfaces such as wettability using captive-bubble contact angle measurement technique; (3) to test the impact of nanostructures on Staphylococcus epidermidis biofilm development. Fabrication of Anodic Alumina Oxide molds was realized by double anodization in oxalic acid. This process was reproducible. The obtained molds present hexagonally arranged 50 nm diameter pores, with a 100 nm interpore distance and a length of 100 nm. Acrylonitrile-butadiene-styrene nanostructures were successfully prepared using a polymer solution and two melt wetting methods. For all methods, the nanopicots were obtained but inside each sample their length was different. One method was selected essentially for industrial purposes and for better reproducibility results. The flat ABS surface presents a slightly hydrophilic character, which remains roughly unchanged after nanostructuration, the increasing apparent wettability observed in that case being explained by roughness effects. Also, the nanostructuration of the polymer surface does not induce any significant effect on Staphylococcus epidermidis adhesion. PMID- 26284925 TI - Central skull base osteomyelitis: a rare but life-threatening disease. AB - We present the case of a 70-year-old non-diabetic patient who presented to the emergency department with unrelenting otalgia. A severe otitis externa (OE) and mastoiditis were treated with broad spectrum antibiotics and surgical drainage. No bacteria was isolated from surgical samples. Because the otalgia persisted, a magnetic resonance (MR) was performed and showed an infiltrating process at the skull base. Biopsies failed to prove malignancy or granulomatosis. The patient's neurological state deteriorated. The suspicion of a skull base osteomyelitis (SBO) was raised and proven by CT-guided biopsies that grew Pseudomonas aeruginosa. Meropenem and ciprofloxacin, given for 8 weeks, lead to a fast clinical improvement and a full recovery. SBO is uncommon, often complicating severe OE. Pseudomonas aeruginosa is the main pathogen. Prompt diagnosis and adequate antibiotherapy are required to lower mortality and morbidity. The diagnosis may be delayed because of unawareness and large differential diagnosis including solid neoplasic tumours, malignant hemopathies and granulomatosis. PMID- 26284924 TI - Cost Resulting from Anti-Tuberculosis Drug Shortages in the United States: A Hypothetical Cohort Study. AB - BACKGROUND: From 2012 through 2014, the United States experienced acute shortages and price escalations of several first-line anti-tuberculosis (TB) medications. Because secondary TB drug regimens are longer and adverse events occur more frequently with them, we sought to conservatively estimate the cost, to patients and the health care system, of TB treatment and medication adverse events from alternative regimens during drug shortages. METHODS: We assessed the cost of treatment for TB disease in the absence of isoniazid (INH), rifampin (RIF), or pyrazinamide (PZA), or both INH and RIF. We simulated adverse events based on published probabilities using a monthly discrete-time stochastic model. For total costs, we summed costs of medications, routine testing, and treatment of adverse events using procedural terminology codes. We report average cost ratios of TB treatment during drug shortages to standard TB treatment. RESULTS: The cost ratio of TB treatment without INH, RIF, or PZA to standard treatment was 1.7 (Range: 1.2, 2.3), 4.9 (Range: 3.2, 7.3), and 1.1 (Range: 0.7, 1.7) times higher, respectively. Without both INH and RIF, the cost ratio was 18.6 (Range: 10.0, 39.0) times higher. When the prices for INH, RIF and PZA were increased, the cost for standard treatment increased by a factor of 2.7 (Range: 1.9, 3.0). The percentage of patients experiencing at least one adverse event while taking standard therapy was 3.9% (Range: 1.3%, 11.8%). This percentage increased to 51.5% (Range: 20.1%, 83.8%) when RIF was unavailable, and increased to 82.5% (Range: 41.2%, 98.5%) when both INH and RIF were unavailable. CONCLUSIONS: Our conservative model illustrates that an interruption in first-line anti-TB medications leads to appreciable additional costs and adverse events for patients. The availability of these drugs in the United States should be ensured. Models that incorporate the effectiveness of alternative regimens, delays in treatment initiation, and TB transmission can provide broader perspectives on the impact of drug shortages. PMID- 26284926 TI - Takayasu's arteritis as the aetiology of unresolved fever in an adult patient with cystic fibrosis. AB - Vasculitis is an unusual complication of cystic fibrosis (CF), normally affecting patients with more severe lung disease. Typical presentation is with skin disease but other organ involvement has been reported. Systemic response to bacterial colonisation and immune complex deposition secondary to chronic airway inflammation is thought to be underlying mechanism of the disease. The authors describe a 28-year-old female Turkish patient with CF presented with fever and arthralgias. The patient was known to have chronic Pseudomonas infection; therefore, a respiratory tract infection was assumed and the patient was treated with imipenem and amikacin for 14 days. Following through investigations of fever of unknown origin, Takayasu's arteritis was identified and the patient responded well to immunosuppression with corticosteroid. PMID- 26284928 TI - Modulation of Cholesterol-Related Gene Expression by Dietary Fiber Fractions from Edible Mushrooms. AB - Mushrooms are a source of dietary fiber (DF) with a cholesterol-lowering effect. However, their underlying mechanisms are poorly understood. The effect of DF enriched fractions from three mushrooms species on cholesterol-related expression was studied in vitro. The Pleurotus ostreatus DF fraction (PDF) was used in mice models to assess its potential palliative or preventive effect against hypercholesterolemia. PDF induced a transcriptional response in Caco-2 cells, suggesting a possible cholesterol-lowering effect. In the palliative setting, PDF reduced hepatic triglyceride likely because Dgat1 was downregulated. However, cholesterol-related biochemical data showed no changes and no relation with the observed transcriptional modulation. In the preventive setting, PDF modulated cholesterol-related genes expression in a manner similar to that of simvastatin and ezetimibe in the liver, although no changes in plasma and liver biochemical data were induced. Therefore, PDF may be useful reducing hepatic triglyceride accumulation. Because it induced a molecular response similar to hypocholesterolemic drugs in liver, further dose-dependent studies should be carried out. PMID- 26284927 TI - B7H1 Expression and Epithelial-To-Mesenchymal Transition Phenotypes on Colorectal Cancer Stem-Like Cells. AB - Cancer stem cells (CSCs) can invade and metastasize by epithelial-to-mesenchymal transition (EMT). However, how they escape immune surveillance is unclear. B7H1 is crucial negative co-stimulatory molecule but little information about whether it works in CSCs. Therefore, we determined the expression of B7H1 and EMT associated markers in colorectal cancer stem-like cells to investigate a possible immunoevasion way of CSCs. We enriched CD133+ colorectal cancer cells which manifested the CSCs-like properties such as higher levels of other stem cell markers Oct-4 and Sox-2, tumor sphere forming ability and more tumorigenic in NOD/SCID mice. These CD133+ cells possess EMT gene expression profile including higher level of Snail, Twist, vimentin, fibronectin and lower level of E cadherin. Moreover, CD133+ cells in both cell line and colorectal cancer tissues expressed high level of negative co-stimulate molecule B7H1. Furthermore, some B7H1+ cancer cells also showed the characteristic of EMT, indicating EMT cells could escape immune attack during metastasis. B7H1 expression and EMT phenotypes on CSCs indicates a possible immunoevasion way. PMID- 26284929 TI - Discovery of Power-Law Growth in the Self-Renewal of Heterogeneous Glioma Stem Cell Populations. AB - BACKGROUND: Accumulating evidence indicates that cancer stem cells (CSCs) drive tumorigenesis. This suggests that CSCs should make ideal therapeutic targets. However, because CSC populations in tumors appear heterogeneous, it remains unclear how CSCs might be effectively targeted. To investigate the mechanisms by which CSC populations maintain heterogeneity during self-renewal, we established a glioma sphere (GS) forming model, to generate a population in which glioma stem cells (GSCs) become enriched. We hypothesized, based on the clonal evolution concept, that with each passage in culture, heterogeneous clonal sublines of GSs are generated that progressively show increased proliferative ability. METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis, we determined whether, with each passage, glioma neurosphere culture generated from four different glioma cell lines become progressively proliferative (i.e., enriched in large spheres). Rather than monitoring self-renewal, we measured heterogeneity based on neurosphere clone sizes (#cells/clone). Log-log plots of distributions of clone sizes yielded a good fit (r>0.90) to a straight line (log(% total clones) = k*log(#cells/clone)) indicating that the system follows a power-law (y = xk) with a specific degree exponent (k = -1.42). Repeated passaging of the total GS population showed that the same power-law was maintained over six passages (CV = 1.01 to -1.17). Surprisingly, passage of either isolated small or large subclones generated fully heterogeneous populations that retained the original power-law dependent heterogeneity. The anti-GSC agent Temozolomide, which is well known as a standard therapy for glioblastoma multiforme (GBM), suppressed the self-renewal of clones, but it never disrupted the power-law behavior of a GS population. CONCLUSIONS/SIGNIFICANCE: Although the data above did not support the stated hypothesis, they did strongly suggest a novel mechanism that underlies CSC heterogeneity. They indicate that power-law growth governs the self-renewal of heterogeneous glioma stem cell populations. That the data always fit a power-law suggests that: (i) clone sizes follow continuous, non-random, and scale-free hierarchy; (ii) precise biologic rules that reflect self-organizing emergent behaviors govern the generation of neurospheres. That the power-law behavior and the original GS heterogeneity are maintained over multiple passages indicates that these rules are invariant. These self-organizing mechanisms very likely underlie tumor heterogeneity during tumor growth. Discovery of this power-law behavior provides a mechanism that could be targeted in the development of new, more effective, anti-cancer agents. PMID- 26284931 TI - Depression Following gamma-Hydroxybutyrate Withdrawal: A Case Report. PMID- 26284930 TI - A Comparison between Transcriptome Sequencing and 16S Metagenomics for Detection of Bacterial Pathogens in Wildlife. AB - BACKGROUND: Rodents are major reservoirs of pathogens responsible for numerous zoonotic diseases in humans and livestock. Assessing their microbial diversity at both the individual and population level is crucial for monitoring endemic infections and revealing microbial association patterns within reservoirs. Recently, NGS approaches have been employed to characterize microbial communities of different ecosystems. Yet, their relative efficacy has not been assessed. Here, we compared two NGS approaches, RNA-Sequencing (RNA-Seq) and 16S metagenomics, assessing their ability to survey neglected zoonotic bacteria in rodent populations. METHODOLOGY/PRINCIPAL FINDINGS: We first extracted nucleic acids from the spleens of 190 voles collected in France. RNA extracts were pooled, randomly retro-transcribed, then RNA-Seq was performed using HiSeq. Assembled bacterial sequences were assigned to the closest taxon registered in GenBank. DNA extracts were analyzed via a 16S-metagenomics approach using two sequencers: the 454 GS-FLX and the MiSeq. The V4 region of the gene coding for 16S rRNA was amplified for each sample using barcoded universal primers. Amplicons were multiplexed and processed on the distinct sequencers. The resulting datasets were de-multiplexed, and each read was processed through a pipeline to be taxonomically classified using the Ribosomal Database Project. Altogether, 45 pathogenic bacterial genera were detected. The bacteria identified by RNA-Seq were comparable to those detected by 16S-metagenomics approach processed with MiSeq (16S-MiSeq). In contrast, 21 of these pathogens went unnoticed when the 16S-metagenomics approach was processed via 454-pyrosequencing (16S-454). In addition, the 16S-metagenomics approaches revealed a high level of coinfection in bank voles. CONCLUSIONS/SIGNIFICANCE: We concluded that RNA-Seq and 16S-MiSeq are equally sensitive in detecting bacteria. Although only the 16S MiSeq method enabled identification of bacteria in each individual reservoir, with subsequent derivation of bacterial prevalence in host populations, and generation of intra-reservoir patterns of bacterial interactions. Lastly, the number of bacterial reads obtained with the 16S-MiSeq could be a good proxy for bacterial prevalence. PMID- 26284932 TI - Long-Term Treatment Outcome in Adult Male Prisoners With Attention Deficit/Hyperactivity Disorder: Three-Year Naturalistic Follow-Up of a 52-Week Methylphenidate Trial. AB - Despite high rates of attention-deficit/hyperactivity disorder (ADHD) among adult lawbreakers, particularly the long-term effects of ADHD pharmacotherapy remain unclear, not the least because of ethical challenges with preventing control subjects in randomized controlled trials from receiving medication over prolonged time. We followed up adult male prisoners with ADHD who completed a 5-week randomized, double-blind, placebo-controlled trial followed by a 47-week open label extension of osmotic-release oral system methylphenidate in a Swedish high security prison from 2007 to 2010 (ClinicalTrials.gov: NCT00482313). Twenty-five trial completers were prospectively followed up clinically 1 year (24/25, 96% participated fully or in part) and 3 years (20/25, 80% participation) after trial regarding ADHD symptoms (observer and self-reports), psychosocial functioning, substance misuse, and criminal reoffending. Methylphenidate-related improvements in ADHD symptoms and psychosocial functioning obtained during the 52-week trial were maintained at 1- and 3-year follow-ups. Specifically, after 3 years, 75% (15/20) of the respondents had been released from prison, and 67% of these (10/15) had employment, usually full time. In contrast, nonmedicated respondents at the 3-year follow-up (5/20) reported more ADHD symptoms, functional impairment, and substance misuse compared with currently medicated respondents (15/20). Further, 40% of the respondents self-reported reoffending, indicating a substantially lower relapse rate than expected (70%-80%).In summary, although these observations need validation from new and larger samples, positive effects were maintained after 4 years of methylphenidate treatment. Most study completers were employed and had no relapse in substance misuse or criminality. These results suggest that motivational support and continued medication are important for improved outcome in adult criminal offenders with ADHD. PMID- 26284933 TI - Depletion of the SR-Related Protein TbRRM1 Leads to Cell Cycle Arrest and Apoptosis-Like Death in Trypanosoma brucei. AB - Arginine-Serine (RS) domain-containing proteins are RNA binding proteins with multiple functions in RNA metabolism. In mammalian cells this group of proteins is also implicated in regulation and coordination of cell cycle and apoptosis. In trypanosomes, an early branching group within the eukaryotic lineage, this group of proteins is represented by 3 members, two of them are SR proteins and have been recently shown to be involved in rRNA processing as well as in pre-mRNA splicing and stability. Here we report our findings on the 3rd member, the SR related protein TbRRM1. In the present study, we showed that TbRRM1 ablation by RNA-interference in T. brucei procyclic cells leads to cell-cycle block, abnormal cell elongation compatible with the nozzle phenotype and cell death by an apoptosis-like mechanism. Our results expand the role of the trypanosomal RS domain containing proteins in key cellular processes such as cell cycle and apoptosis-like death, roles also carried out by the mammalian SR proteins, and thus suggesting a conserved function in this phylogenetically conserved protein family. PMID- 26284934 TI - De Novo Transcriptome Analysis of Allium cepa L. (Onion) Bulb to Identify Allergens and Epitopes. AB - Allium cepa (onion) is a diploid plant with one of the largest nuclear genomes among all diploids. Onion is an example of an under-researched crop which has a complex heterozygous genome. There are no allergenic proteins and genomic data available for onions. This study was conducted to establish a transcriptome catalogue of onion bulb that will enable us to study onion related genes involved in medicinal use and allergies. Transcriptome dataset generated from onion bulb using the Illumina HiSeq 2000 technology showed a total of 99,074,309 high quality raw reads (~20 Gb). Based on sequence homology onion genes were categorized into 49 different functional groups. Most of the genes however, were classified under 'unknown' in all three gene ontology categories. Of the categorized genes, 61.2% showed metabolic functions followed by cellular components such as binding, cellular processes; catalytic activity and cell part. With BLASTx top hit analysis, a total of 2,511 homologous allergenic sequences were found, which had 37-100% similarity with 46 different types of allergens existing in the database. From the 46 contigs or allergens, 521 B-cell linear epitopes were identified using BepiPred linear epitope prediction tool. This is the first comprehensive insight into the transcriptome of onion bulb tissue using the NGS technology, which can be used to map IgE epitopes and prediction of structures and functions of various proteins. PMID- 26284935 TI - Possibility for the Conjugated Use of Photodynamic Therapy and Electrosurgical Devices. AB - Because tissue optics limits the treated volume during anti-tumor Photodynamic Therapy (PDT), its conjugation with prior tissue debulking has been suggested clinically. In this context, the conjugation of radiofrequency ablation and PDT has already been demonstrated. However, the basic principles that enable the success of these protocols have not been discussed. This proof-of-principle study analyzes the possibility of conjugating electrosurgery (ES) and PDT, analyzing different sequences of photosensitizer (PS) administration in an animal model. The animals were distributed over five groups: ES, PS+Light, PS+ES, ES+PS+Light and PS+ES+Light. The PS Photogem was administered systemically. An electrosurgical unit (480 kHz) was used to remove a portion of the liver, leaving a plane surface for PDT illumination (630 nm, 150 J/cm2). Fluorescence was collected during the stages of the experiment to monitor the PS accumulation. After 30 hours, histological processing was performed. The fluorescence spectra revealed strong Photogem emission in both administration sequences (ES+PS; PS+ES), and little PS bleach after ES was observed. The maximum necrosis depth was observed for the PS+ES+Light group-(716 +/- 75) MUm-higher than its respective control group (160 +/- 28) MUm, proving successful conjugation. Histological features from ES and PDT on both conjugation sequences were observed. Pre-photosensitized tissue presented decreased ES-related thermal damage. A simple physical hypothesis, based on the Joule effect and the tissue electrical conductivity, was proposed to support these findings. In conclusion, the results successfully demonstrated the possibility of conjugating ES and PDT in a single protocol. PMID- 26284936 TI - New Rimocidin/CE-108 Derivatives Obtained by a Crotonyl-CoA Carboxylase/Reductase Gene Disruption in Streptomyces diastaticus var. 108: Substrates for the Polyene Carboxamide Synthase PcsA. AB - The rimJ gene, which codes for a crotonyl-CoA carboxylase/reductase, lies within the biosynthetic gene cluster for two polyketides belonging to the polyene macrolide group (CE-108 and rimocidin) produced by Streptomyces diastaticus var. 108. Disruption of rimJ by insertional inactivation gave rise to a recombinant strain overproducing new polyene derivatives besides the parental CE-108 (2a) and rimocidin (4a). The structure elucidation of one of them, CE-108D (3a), confirmed the incorporation of an alternative extender unit for elongation step 13. Other compounds were also overproduced in the fermentation broth of rimJ disruptant. The new compounds are in vivo substrates for the previously described polyene carboxamide synthase PcsA. The rimJ disruptant strain, constitutively expressing the pcsA gene, allowed the overproduction of CE-108E (3b), the corresponding carboxamide derivative of CE-108D (3a), with improved pharmacological properties. PMID- 26284937 TI - Quality of Life and Body Mass Index in Overweight Adult Women with Polycystic Ovary Syndrome During a Lifestyle Modification Program. AB - OBJECTIVE: To evaluate changes in body mass index (BMI) and health-related quality of life (HRQoL), including an acne parameter, of overweight adult women with polycystic ovary syndrome (PCOS) during a lifestyle modification program. DESIGN: Prospective longitudinal within-patient study. SETTING: Department of Reproductive Medicine of the Ghent University Hospital (Belgium). PARTICIPANTS: Thirty-three overweight (BMI >= 25 kg/m2) women with PCOS between age 18 and 43 years. METHODS: Participants followed a 24-week lifestyle modification program consisting of a diet, exercise, and psychological subprogram. BMI was assessed at Weeks 0, 8, 16, and 24 of the program. The HRQoL was measured at Week 0, 12, and 24 of the program using the PolyCystic Ovary Syndrome Questionnaire (PCOSQ) and a Visual Analogue Scale (VAS) to evaluate the influence of acne on HRQoL. RESULTS: During a 24-week period no significant decrease in BMI occurred (mean difference = 1.71, 95% confidence interval [CI] [-1.38, 4.81]. During that period, there was a significant positive evolution of the total PCOSQ score, F(2, 37.5) = 23.7, the emotions, F(2, 37.9) = 4.2, weight, F(2, 42.1) = 24.8, body hair, F(2, 35.6) = 3.3, and infertility problems domain scores, F(2, 43.1) = 15.64, of the PCOSQ, as well as of the acne VAS score, F(2, 29.3) = 4.2. These effects primarily occurred during the first 12 weeks. CONCLUSION: In spite of no significant changes in BMI, the HRQoL of overweight adult women with PCOS significantly improved during a 24 week lifestyle modification program. PMID- 26284938 TI - Alcohol Dehydrogenase-1B (rs1229984) and Aldehyde Dehydrogenase-2 (rs671) Genotypes Are Strong Determinants of the Serum Triglyceride and Cholesterol Levels of Japanese Alcoholic Men. AB - BACKGROUND: Elevated serum triglyceride (TG) and high-density-lipoprotein cholesterol (HDL-C) levels are common in drinkers. The fast-metabolizing alcohol dehydrogenase-1B encoded by the ADH1B*2 allele (vs. ADH1B*1/*1 genotype) and inactive aldehyde dehydrogenase-2 encoded by the ALDH2*2 allele (vs. ALDH2*1/*1 genotype) modify ethanol metabolism and are prevalent (~90% and ~40%, respectively) in East Asians. We attempted to evaluate the associations between the ADH1B and ALDH2 genotypes and lipid levels in alcoholics. METHODS: The population consisted of 1806 Japanese alcoholic men (>=40 years) who had undergone ADH1B and ALDH2 genotyping and whose serum TG, total cholesterol, and HDL-C levels in the fasting state had been measured within 3 days after admission. RESULTS: High serum levels of TG (>=150 mg/dl), HDL-C (>80 mg/dl), and low-density-lipoprotein cholesterol (LDL-C calculated by the Friedewald formula >=140 mg/dl) were observed in 24.3%, 16.8%, and 15.6%, respectively, of the subjects. Diabetes, cirrhosis, smoking, and body mass index (BMI) affected the serum lipid levels. Multivariate analysis revealed that the presence of the ADH1B*2 allele and the active ALDH2*1/*1 genotype increased the odds ratio (OR; 95% confidence interval) for a high TG level (2.22 [1.67-2.94] and 1.39 [0.99 1.96], respectively), and decreased the OR for a high HDL-C level (0.37 [0.28 0.49] and 0.51 [0.37-0.69], respectively). The presence of the ADH1B*2 allele decreased the OR for a high LDL-C level (0.60 [0.45-0.80]). The ADH1B*2 plus ALDH2*1/*1 combination yielded the highest ORs for high TG levels and lowest OR for a high HDL-C level. The genotype effects were more prominent in relation to the higher levels of TG (>=220 mg/dl) and HDL-C (>=100 mg/dl). CONCLUSIONS: The fast-metabolizing ADH1B and active ALDH2, and especially a combination of the two were strongly associated with higher serum TG levels and lower serum HDL-C levels of alcoholics. The fast-metabolizing ADH1B was associated with lower serum LDL-C levels. PMID- 26284940 TI - Split skin graft "from scalp to scalp" for repairing large surgical defects. PMID- 26284941 TI - A Multisite Study of Environmental Correlates of Active Commuting to School in Mexican Children. AB - BACKGROUND: Mexican children often use active commuting to school (ACS). In order to maintain high levels of ACS it is important to understand correlates of ACS in this population. However, most evidence comes from high-income countries (HICs). We examined multilevel correlates of ACS in children attending public schools in 3 Mexican cities. METHODS: Information on 1191 children (grades 3 to 5) attending 26 schools was retrieved from questionnaires, neighborhood audits, and geographic information systems data. Multilevel logistic modeling was used to explore individual and environmental correlates of ACS at 400-m and 800-m buffers surrounding schools. RESULTS: Individual positive correlates for ACS included age (6-8 years vs 9-11 years, odds ratio [OR] = 1.5; 6-8 years vs >=12 years: OR = 2.1) and >= 6 adults at home (OR = 2.0). At the 400-m buffer, more ACS was associated with lower walkability (OR = 0.87), presence of posted speed limits (< 6% vs > 12%: OR = 0.36) and crossing aids (< 6% vs 6-20%: OR = 0.25; > 20%: OR = 0.26), as well as higher sidewalk availability (< 70% vs > 90%: OR = 4.5). Similar relationships with speed limits and crossing aids were observed at the 800m buffer. CONCLUSIONS: Findings contrast with those reported in HICs, underscoring the importance of considering the local context when developing strategies to promote ACS. Future studies are needed to replicate these relationships and investigate the longitudinal impact of improving active transportation infrastructure and policies. PMID- 26284939 TI - Breaking immune tolerance by targeting Foxp3(+) regulatory T cells mitigates Alzheimer's disease pathology. AB - Alzheimer's disease (AD) is a neurodegenerative disorder in which chronic neuroinflammation contributes to disease escalation. Nevertheless, while immunosuppressive drugs have repeatedly failed in treating this disease, recruitment of myeloid cells to the CNS was shown to play a reparative role in animal models. Here we show, using the 5XFAD AD mouse model, that transient depletion of Foxp3(+) regulatory T cells (Tregs), or pharmacological inhibition of their activity, is followed by amyloid-beta plaque clearance, mitigation of the neuroinflammatory response and reversal of cognitive decline. We further show that transient Treg depletion affects the brain's choroid plexus, a selective gateway for immune cell trafficking to the CNS, and is associated with subsequent recruitment of immunoregulatory cells, including monocyte-derived macrophages and Tregs, to cerebral sites of plaque pathology. Our findings suggest targeting Treg mediated systemic immunosuppression for treating AD. PMID- 26284942 TI - Impact of Type-2 Diabetes Time Since Diagnosis on Elderly Women Gait and Functional Status. AB - BACKGROUND AND PURPOSE: The gait, mobility and lower-limb strength alterations of diabetic elderly women without symptoms of diabetic neuropathy in different periods of the chronic disease can contribute to an early functional diagnosis, allowing prevention of adverse outcomes like falls and disability. This could also contribute to the development of interventions, cures and physiotherapy practice for this population. The aim of this study was to verify the impact of type-2 diabetes mellitus time since diagnosis on gait and functional status of elderly women. METHODS: Eighty-two diabetic elderly women without neuropathic symptoms participated and divided in two groups: 1) 49 elderly (71.4 +/- 4.8 years) with less than 10 years of type-2 diabetes mellitus diagnosis, and 2) 33 elderly (70 +/- 4.5 years) with 10 or more years of type-2 diabetes mellitus diagnosis. Outcomes were spatiotemporal gait parameters (speed, cadence, step length, base of support, stance time, swing time, and double support time) assessed through GAITRite(r) system, and functional status assessed using the Timed Up and Go test and five times sit-to-stand test. To compare spatiotemporal gait variables and performance on functional tests between groups, multivariate analysis of variance and Mann-Whitney test were performed, respectively. RESULTS: The group with 10 or more years of diagnosis showed lower gait speed and smaller step length (112.3 cm/s; 59.2 cm) compared with the group with less than 10 years of diagnosis (122.9 cm/s; 62.4 cm). In relation to Timed Up and Go test and five times sit-to-stand test, there were no statistically significant differences between the groups. CONCLUSION: Type-2 diabetes mellitus time since diagnosis has a negative impact on gait speed and step length, but not on functional status of the elderly women. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26284943 TI - alpha1 and alpha2-adrenergic agonists on cirrhotic patients with refractory ascites. PMID- 26284944 TI - pK(A) in proteins solving the Poisson-Boltzmann equation with finite elements. AB - Knowledge on pK(A) values is an eminent factor to understand the function of proteins in living systems. We present a novel approach demonstrating that the finite element (FE) method of solving the linearized Poisson-Boltzmann equation (lPBE) can successfully be used to compute pK(A) values in proteins with high accuracy as a possible replacement to finite difference (FD) method. For this purpose, we implemented the software molecular Finite Element Solver (mFES) in the framework of the Karlsberg+ program to compute pK(A) values. This work focuses on a comparison between pK(A) computations obtained with the well established FD method and with the new developed FE method mFES, solving the lPBE using protein crystal structures without conformational changes. Accurate and coarse model systems are set up with mFES using a similar number of unknowns compared with the FD method. Our FE method delivers results for computations of pK(A) values and interaction energies of titratable groups, which are comparable in accuracy. We introduce different thermodynamic cycles to evaluate pK(A) values and we show for the FE method how different parameters influence the accuracy of computed pK(A) values. PMID- 26284947 TI - A Remarkably Simple Hybrid Surfactant-NHC Ligand, Its Gold-Complex, and Application in Micellar Catalysis. AB - A combination of an N-heterocyclic carbene (NHC) ligand and a structurally simple surfactant has been realized, the hybrid surfactant-NHC. The related gold complex was synthesized, fully characterized, and applied in catalysis. This remarkably simple strategy allows, in combination with a co-surfactant, the application of gold catalysis in water. PMID- 26284948 TI - Functionalization of Intramolecular Frustrated Lewis Pairs by 1,1-Carboboration with Conjugated Enynes. AB - The vicinal P/B frustrated Lewis pair (FLP) Mes2PCH2CH2B(C6F5)2 undergoes 1,1 carboboration reactions with the Me3Si-substituted enynes to give ring-enlarged functionalized C3-bridged P/B FLPs. These serve as active FLPs in the activation of dihydrogen to give the respective zwitterionic [P]H(+)/[B]H(-) products. One such product shows activity as a metal-free catalyst for the hydrogenation of enamines or a bulky imine. The ring-enlarged FLPs contain dienylborane functionalities that undergo "bora-Nazarov"-type ring-closing rearrangements upon photolysis. A DFT study had shown that the dienylborane cyclization of such systems itself is endothermic, but a subsequent C6F5 migration is very favorable. Furthermore, substituted 2,5-dihydroborole products are derived from cyclization and C6F5 migration from the photolysis reaction. In the case of the six-membered annulation product, a subsequent stereoisomerization reaction takes place and the resultant compound undergoes a P/B FLP 1,2-addition reaction with a terminal alkyne with rearrangement. PMID- 26284952 TI - Relationships between gastrointestinal symptoms, uncertainty, and perceived recovery in patients with gastric cancer after gastrectomy. AB - This study examines relationships between gastrointestinal symptoms, uncertainty, and perceived recovery in gastric cancer patients after gastrectomy. Data were collected from 146 patients at an outpatient clinic of a university hospital in Seoul, Korea from October to November 2012. The Gastrointestinal Symptoms Rating Scale, the Mishel Uncertainty in Illness Scale, and questions on perceived recovery of physical, psychological, and social functions were analyzed. High gastrointestinal symptom scores were reported in women younger patients (F = 5.55, P = 0.005), and in patients without a family history of gastric cancer. The uncertainty score was higher in patients with low economic (F = 3.84, P = 0.024) and educational status and no family history. Regression analysis revealed uncertainty was the strongest factor associated with recovery. Nurses can assist patients and families to predict and deal with health problems by offering education on progress from diagnosis to postoperative management, promoting all aspects of recovery after gastrectomy. PMID- 26284951 TI - Changes in cardiac biomarkers with bortezomib treatment in patients with advanced cardiac amyloidosis. PMID- 26284954 TI - The kiss of sleeping beauty. PMID- 26284953 TI - Patterns of weight-control behavior among 15 year old girls. AB - OBJECTIVE: The objectives were to identify and predict patterns of weight-control behavior in 15 years old (yo) girls and to examine weight-control group differences in energy intake. METHOD: Participants included 166 girls assessed every 2 years (ys) from age 5 to 15. Latent class analysis was used to identify patterns of weight-control behaviors. Antecedent variables (e.g., inhibitory control at 7 ys), and concurrent variables (e.g., BMI and dietary intake at 15 ys) were included as predictors. Assessments were a combination of survey, interview, and laboratory measures. RESULTS: Latent class analysis (LCA) identified four classes of weight-control behaviors, nondieters (26%), and three dieting groups, namely lifestyle (16%), dieters (43%), and extreme dieters (17%). Levels of restraint, weight concerns, and dieting frequency increased across groups, from nondieters to extreme dieters. Body mass index (BMI) at 5 ys and inhibitory control at 7 ys predicted weight-control group at 15 ys; for example, with every one point decrease in inhibitory control, girls were twice as likely to be extreme dieters than nondieters. Girls in the extreme dieters group were mostly classified as under-reporters and had the lowest self-reported intake, but ate significantly more in the laboratory. DISCUSSION: Among 15 yo girls, "dieting" includes a range of both healthy and unhealthy behaviors. Risk factors for membership in a weight-control group are present as early as 5 ys. Patterns of intake in the laboratory support the view that lower reported energy intake by extreme dieters is likely due under-reporting as an intent to decrease intake, not actual decreased intake. PMID- 26284955 TI - Structural and functional correlates of a quantitative autistic trait measured using the social responsive scale in neurotypical male adolescents. AB - Behaviors associated with autism spectrum disorder (ASD) have been suggested to be considered as quantitative traits. This study investigated the structural and functional correlates of autistic traits measured using the Social Responsiveness Scale (SRS) in neurotypical adolescents. Twenty-six neurotypical male adolescents (12-18 years old) were recruited for this study and underwent structural and resting functional magnetic resonance image scanning, and intelligence quotient and SRS evaluations. We used the automated surface-based method (FreeSurfer) to measure cortical thickness and seed-based functional connectivity (FC) analysis to derive the FC map of the dorsal anterior cingulate (dACC). Brain-wise regression analyses of cortical thickness and FC maps on SRS scores were performed using a general linear model. The results indicated that higher autistic trait ratings of total SRS scores were associated with a thinner cortex in the left insula, right insula, and right superior temporal gyrus. Furthermore, we observed that only higher scores of social awareness were correlated with increased FC between the dACC and right superior temporal gyrus and decreased FC between the dACC and right putamen and thalamus. These results indicated that a quantitative trait in social cognition is associated with structural and connectivity variations linked to ASD patients. Autism Res 2016, 9: 570-578. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc. PMID- 26284956 TI - Sodium channel haploinsufficiency and structural change in ventricular arrhythmogenesis. AB - Normal cardiac excitation involves orderly conduction of electrical activation and recovery dependent upon surface membrane, voltage-gated, sodium (Na(+) ) channel alpha-subunits (Nav 1.5). We summarize experimental studies of physiological and clinical consequences of loss-of-function Na(+) channel mutations. Of these conditions, Brugada syndrome (BrS) and progressive cardiac conduction defect (PCCD) are associated with sudden, often fatal, ventricular tachycardia (VT) or fibrillation. Mouse Scn5a(+/-) hearts replicate important clinical phenotypes modelling these human conditions. The arrhythmic phenotype is associated not only with the primary biophysical change but also with additional, anatomical abnormalities, in turn dependent upon age and sex, each themselves exerting arrhythmic effects. Available evidence suggests a unified binary scheme for the development of arrhythmia in both BrS and PCCD. Previous biophysical studies suggested that Nav 1.5 deficiency produces a background electrophysiological defect compromising conduction, thereby producing an arrhythmic substrate unmasked by flecainide or ajmaline challenge. More recent reports further suggest a progressive decline in conduction velocity and increase in its dispersion particularly in ageing male Nav 1.5 haploinsufficient compared to WT hearts. This appears to involve a selective appearance of slow conduction at the expense of rapidly conducting pathways with changes in their frequency distributions. These changes were related to increased cardiac fibrosis. It is thus the combination of the structural and biophysical changes both accentuating arrhythmic substrate that may produce arrhythmic tendency. This binary scheme explains the combined requirement for separate, biophysical and structural changes, particularly occurring in ageing Nav 1.5 haploinsufficient males in producing clinical arrhythmia. PMID- 26284957 TI - Aggression in non-human vertebrates: Genetic mechanisms and molecular pathways. AB - Aggression is an adaptive behavioral trait that is important for the establishment of social hierarchies and competition for mating partners, food, and territories. While a certain level of aggression can be beneficial for the survival of an individual or species, abnormal aggression levels can be detrimental. Abnormal aggression is commonly found in human patients with psychiatric disorders. The predisposition to aggression is influenced by a combination of environmental and genetic factors and a large number of genes have been associated with aggression in both human and animal studies. In this review, we compare and contrast aggression studies in zebrafish and mouse. We present gene ontology and pathway analyses of genes linked to aggression and discuss the molecular pathways that underpin agonistic behavior in these species. (c) 2015 Wiley Periodicals, Inc. PMID- 26284958 TI - Somatotrope GHRH/GH/IGF-1 axis at the crossroads between immunosenescence and frailty. AB - Immunosenescence, characterized by complex modifications of immunity with age, could be related to frailty syndrome in elderly individuals, leading to an inadequate response to minimal aggression. Functional decline (i.e., the loss of ability to perform activities of daily living) is related to frailty and decreased physiological reserves and is a frequent outcome of hospitalization in older patients. Links between immunosenescence and frailty have been explored and 20 immunological parameters, including insulin-like growth factor-1 (IGF-1), thymopoeisis, and telomere length, were shown to be affected in elderly patients with functional decline. A strong relationship between IGF-1 and thymic ouput was evidenced. IGF-1, a mediator of growth hormone (GH), was subsequently shown to induce interleukin-7 secretion in cultured primary human thymic epithelial cells. We are exploring the stress hypothesis in which an acute stressor is used as the discriminator of frailty susceptibility. GH can counteract the deleterious immunosuppressive effects of stress-induced steroids. Under nonstress conditions, the immunosenescent system preserves physiological responses, while under stress conditions, the combination of immunosenescence and a defect in the somatotrope axis might lead to functional decline. PMID- 26284959 TI - Assessment of the Role Played by N-propanol Found in Postmortem Blood in the Discrimination Between Antemortem Consumption and Postmortem Formation of Ethanol Using Rats. AB - This study disproves the reliability of n-propanol as a biomarker to establish whether the ethanol found in postmortem blood is derived from antemortem ingestion or postmortem putrefactive processes. Two groups of rats were given ethanol or normal saline solution, respectively, and sacrificed 1.5 h later. After putrefaction, blood and, in a few cases, urine samples from the rats were analyzed for ethanol and n-propanol by head-space gas chromatography equipped with flame ionization detection. Although the concentration ratios of ethanol/n propanol in the postmortem blood collected from the bodies without prior alcohol consumption were expected to be <20 (as per limited case reports and previous in vitro studies), in samples from several rats that were on saline solution, this ratio was found to exceed 20. In conclusion, the concentration ratio of ethanol/n propanol in postmortem blood does not allow for the discernment between antemortem ingestion and the postmortem synthesis of ethanol. PMID- 26284960 TI - Radial Artery Bypass for Intractable Vertebrobasilar Insufficiency: Case Series and Review of the Literature. AB - BACKGROUND: Vertebrobasilar insufficiency resulting from embolism, atherosclerosis, or arterial dissection has long been a challenge for successful management and outcomes. The main treatment options include medical therapy, angioplasty and stenting, and surgical revascularization. Unlike cardiac or peripheral vascular revascularization, large randomized trials with cerebrorevascularization have not revealed favorable outcomes. In patients who have failed maximal medical therapy, and having persistent debilitating symptomology, cerebral revascularization may still be a viable option. METHODS: We report 3 patients who presented with symptoms of vertebrobasilar ischemia. The diagnosis was verified by computerized tomographic arteriography and digital subtraction angiography. RESULTS: These patients subsequently underwent revascularization with a radial artery graft. We also present a comprehensive review of the literature of treatment for vertebrobasilar insufficiency. CONCLUSIONS: Surgical revascularization should be considered in the posterior circulation in the rare subset of patients with VBI, who remain symptomatic despite having a protracted course of maximal medical therapy with large- and medium-sized vessel occlusions and poor collateral circulation. PMID- 26284961 TI - In the Final Act. PMID- 26284964 TI - Infrared Photodissociation Spectroscopy of the Ni(O2)n(+) (n = 2-4) Cation Complexes. AB - The infrared spectra of mass-selected Ni(O2)n(+) (n = 2-4) and their argon-tagged complexes are measured by infrared photodissociation spectroscopy in the gas phase. The experimental spectra provide distinctive patterns allowing the determination of their geometric and electronic structures by comparison with the simulated vibrational spectra from density functional theory calculations. The [Ni(O2)2Ar2](+) cation complex was determined to have D2h symmetry involving a Ni(O2)2(+) core ion with two equivalent superoxide ligands side-on bound to a Ni(3+) cation center. The higher Ni(O2)3(+) and Ni(O2)4(+) cation complexes were determined to have structures with a chemically bound Ni(O2)2(+) core ion that is weakly coordinated by neutral O2 molecule(s). PMID- 26284963 TI - Challenges to get axenic cultures of Trichomonas spp. - A new approach in eradication of contaminants and maintenance of laboratory microbiological cultures. AB - Contamination of microbiological and cell cultures is a major problem in many scientific and clinical laboratories as well as bioproduct manufacturers worldwide. In the current study we established a rapid (9day) method to detect and eliminate fungal and bacterial contamination in cultures of the unicellular eukaryote Trichomonas spp. The developed method combines identification of the contaminating microorganisms using PCR and sequencing of the 16/18S regions followed by phylogenetic analysis. The next step was a phylogeny-guided selection of antibiotic treatments. We then used a two-step propidium iodide-resorufin assay to test the effect of selected antibiotics. The result was a quick and worthwhile purification of trichomonad laboratory cultures. Our workflow may also be implemented to obtain new isolates of trichomonads from clinical samples if initial broad-spectrum antibiotic therapy fails. PMID- 26284965 TI - Paternity analysis based on NGM SElect system in the Medical and Forensic Genetics Laboratory, Department of Forensic Medicine, Medical University of Lodz. AB - The aim of the study was to evaluate the usefulness of the NGM SElect multiplex kit for paternity testing in the population of central Poland, and compare it with the IDENTIFILER system. The study material consisted of buccal swabs taken from individuals who reported to the Medical and Forensic Genetics Laboratory in Lodz. Samples from 450 trio cases of disputed paternity carried out in 2010-2014 were investigated. Genomic DNA was extracted from buccal swabs collected from 1,350 individuals using the Swab kit (A and A Biotechnology) according to the manufacturer's protocol. DNA amplification was performed using the AmpFlSTR(r) NGM SelectTM PCR Amplification Kit (Life Technologies). PCR products were separated by capillary electrophoresis using HID 3500 Genetic Analyzer. In the analyzed cases with paternity confirmation in the NGM SElect system, the maximum value of PI was 3.9 * 1012, which corresponds to the probability of paternity W = 99.9999999999%. It was thus significantly higher than analogical parameters obtained in the IDENTIFILER system (PI = 6.0 * 1010, W = 99.99999999%). The NGM SElect kit was unable to resolve just one case out of 450, which represents only 0.2% of all analyzed disputed paternity cases. The study showed the SE33 (ACTBP2) locus to have the highest evidence value in paternity analysis out of all investigated autosomal STRs. PMID- 26284966 TI - Medico-legal and legal-penal aspects of expert opinions and adjudication in cases of intoxications with intoxicating agents and ethanol-like intoxicants. AB - INTRODUCTION: The available legal regulations in Poland do not define the concentration thresholds enabling to differentiate between the states of "after use" versus "under the influence" of a drug, as it is in the case of alcohol. The aim of the study was to analyse jurisdiction in cases regarding the evaluation of the effects of intoxicating agents and ethanol-like intoxicants and to identify ambiguities and gaps in the applicable regulations leading to problems in preparing expert opinions. MATERIAL AND METHODS: The material included the opinions of experts in the field of toxicology and forensic medicine made by the Department of Forensic Medicine in Lublin in the years 2009-2011 and records obtained in the process of inquiry from the regional prosecutor's offices and courts in 52 cases. RESULTS: Amongst 52 cases in which the ordered toxicology examinations demonstrated the presence of intoxicating agents in drivers' blood (tetrahydrocannabinols in 39 and amphetamine in 21 cases) in 2 cases petty offence proceedings were instituted (Art. 87 of the Petty Offence Code) although high concentrations of xenobiotics indicated the state of being "under the influence" of a narcotic drug (Art. 178a of the Penal Code). Three cases were discontinued despite expert opinions that the drivers were at least in the after narcotic use state. In only 3 cases were witnesses asked to provide testimony about the circumstances of the driver's conduct. CONCLUSIONS: The analysis has demonstrated that judicial bodies expect forensic expertise based exclusively on toxicological examination results; when expert findings are inconclusive, they only administer litigations opportunistically applying the principle of the presumption of innocence understood literally. Considering the above, threshold values of "use" and "influence" of the most commonly detected drugs should be urgently determined. PMID- 26284967 TI - Pharyngitis - fatal infectious disease or medical error? AB - Reporting on adverse events is essential to create a culture of safety, which focuses on protecting doctors and patients from medical errors. We present a fatal case of Streptococcus C pharyngitis in a 56-year-old man. The clinical course and the results of additional diagnostics and autopsy showed that sepsis followed by multiple organ failure was the ultimate cause of death. The clinical course appeared fatal due to a chain of adverse events, including errors made by the physicians caring for the patient for 10 days. PMID- 26284968 TI - The role of respiratory failure caused by congenital central nervous system abnormalities and the effect of beta-casomorphins in sudden infant death syndrome pathogenesis. AB - The aim of the paper is to discuss the role of respiratory failure caused by endogenous (both structural and functional) abnormalities in the central nervous system and exogenous food-derived opioid-like peptides in the pathogenesis of sudden infant death syndrome (SIDS). By stimulating MU-opioid receptors, opioid like peptides may suppress the tonic activity of the respiratory centre in the brain stem. PMID- 26284969 TI - Angiogenesis in brain contusion. AB - In the forensic medicine, objective and, if possible, the most accurate determination of the age - the time of the brain contusion, has practical significance. In our previous work, we discussed the importance of the neuron cytoskeleton proteins - neurofilaments, in this area. The purpose of this paper is to present the possibilities of using the phenomenon of angiogenesis in the brain contusions, to determine its age, on the basis of previous studies in animal models and in human biological material. The current review of the literature showed no conclusive data that would allow use morphological changes in angiogenesis to determine the age of the brain contusion in forensic medical practice. For these reasons, it is reasonable to take a broader research on the human material. PMID- 26284970 TI - Alpha-Synuclein Regulates Neuronal Levels of Manganese and Calcium. AB - Manganese (Mn) may foster aggregation of alpha-synuclein (alphaSyn) contributing to the pathogenesis of PD. Here, we examined the influence of alphaSyn overexpression on distribution and oxidation states of Mn in frozen-hydrated primary midbrain neurons (PMNs) by synchrotron-based X-ray fluorescence (XRF) and X-ray absorption near edge structure spectroscopy (XANES). Overexpression of alphaSyn increased intracellular Mn levels, whereas levels of Ca, Zn, K, P, and S were significantly decreased. Mn oxidation states were not altered. A strong correlation between Cu-/Mn-levels as well as Fe-/Mn-levels was observed in alphaSyn-overexpressing cells. Subcellular resolution revealed a punctate or filament-like perinuclear and neuritic distribution of Mn, which resembled the expression of DMT1 and MnSOD. While overexpression of alphaSyn did not significantly alter the expression patterns of the most-expressed Mn transport proteins (DMT1, VGCC, Fpn1), it attenuated the Mn release from Mn-treated neurons. Thus, these data suggest that alphaSyn may act as an intracellular Mn store. In total, neurotoxicity in PD could be mediated via regulation of transition metal levels and the metal-binding capacity of alphaSyn, which could represent a promising therapeutic target for this neurodegenerative disorder. PMID- 26284971 TI - Effect of IL28B genotype on hepatitis B and C virus infection. AB - Genetic factors play a major role for treatment response and disease progression of chronic hepatitis B (HBV) and C virus (HCV) infection. In 2009 a genome-wide association study (GWAS) identified a single nucleotide polymorphism near the IL28B gene that was associated with treatment-induced viral clearance in chronic HCV infection treated with pegylated interferon-alpha (PEG-IFN) and ribavirin (RBV). Further, another GWAS found an association between IL28B genotype and spontaneous viral clearance in acute HCV infection. The effect on sustained viral response (SVR) could also be observed in patients receiving a triple-therapy with a direct antiviral agent (DAA) combined with PEG-IFN/RBV. In the era of all-oral interferon-free treatment regimens with the combination of different DAAs-with SVR rates exceeding 90%-the effect of IL28B was blunt. In contrast, in HBV several retrospective studies yielded conflicting results of the association of IL28B with PEG-IFN-induced treatment response. PMID- 26284973 TI - Effect of molecular weight and concentration of hyaluronan on cell proliferation and osteogenic differentiation in vitro. AB - Hyaluronan (HA), the simplest glycosaminoglycan and a major component of the extracellular matrix, exists in various tissues. It is involved in some critical biological procedures, including cellular signaling, cell adhesion and proliferation, and cell differentiation. The effect of molecular weight (MW) and concentration of HA on cell proliferation and differentiation was controversial. In this study, we investigated the effect of MW and concentration of HA on the proliferation and osteogenic differentiation of rabbit bone marrow-derived stem cells in vitro. Results showed that high MW HA decreased the cell adhesion rate in a concentration-dependant manner. The cell adhesion rate was decreased by increasing MW of HA. Cell proliferation was significantly enhanced by low MW HA (P < 0.05). The factorial analysis indicated that MW and concentration had an interactive effect on the cell adhesion rate and cell proliferation (P < 0.05). High MW HA increased the mRNA expressions of ALP, RUNX-2 and OCN. The higher the MW was, the higher the mRNA expressions were. The factorial analysis indicated that MW and concentration had an interactive effect on ALP mRNA expression (P < 0.05). HA of higher MW and higher concentration promoted bone formation. These findings provide some useful information in understanding the mechanism underlying the effect of MW and concentration of HA on cell proliferation and differentiation. PMID- 26284972 TI - The Evolution of Aggregative Multicellularity and Cell-Cell Communication in the Dictyostelia. AB - Aggregative multicellularity, resulting in formation of a spore-bearing fruiting body, evolved at least six times independently amongst both eukaryotes and prokaryotes. Amongst eukaryotes, this form of multicellularity is mainly studied in the social amoeba Dictyostelium discoideum. In this review, we summarise trends in the evolution of cell-type specialisation and behavioural complexity in the four major groups of Dictyostelia. We describe the cell-cell communication systems that control the developmental programme of D. discoideum, highlighting the central role of cAMP in the regulation of cell movement and cell differentiation. Comparative genomic studies showed that the proteins involved in cAMP signalling are deeply conserved across Dictyostelia and their unicellular amoebozoan ancestors. Comparative functional analysis revealed that cAMP signalling in D. discoideum originated from a second messenger role in amoebozoan encystation. We highlight some molecular changes in cAMP signalling genes that were responsible for the novel roles of cAMP in multicellular development. PMID- 26284974 TI - Idebenone protects against oxidized low density lipoprotein induced mitochondrial dysfunction in vascular endothelial cells via GSK3beta/beta-catenin signalling pathways. AB - The early stages of the atherosclerotic process are initiated by accumulation of oxidized low-density lipoprotein (oxLDL) and damage to the structure or function of the endothelium. Antioxidant supplementation may be a plausible strategy to prevent atherosclerotic disease by quenching excessive reactive oxidative species. In the present study, we demonstrated that idebenone at suitable concentrations significantly prevented oxLDL-induced endothelial dysfunction. The underlying mechanisms of idebenone included inhibition of oxidative damage, suppression of the down-regulation of Bcl-2 and up-regulation of Bax and cleaved caspase-3 in human umbilical vein endothelial cells (HUVECs) exposed to oxLDL. Moreover, idebenone pretreatment inhibited oxLDL-mediated HUVECs damage by attenuating lipid peroxidation and promoting SOD activity. Finally, pro incubation with idebenone inhibited mitochondrial dysfunction induced by oxLDL through the mitochondrial-dependent apoptotic pathway and GSK3beta/beta-catenin signalling pathways. In summary, idebenone is a promising agent in the treatment or prevention of atherosclerosis via inhibiting oxidative stress and improving mitochondrial function. PMID- 26284975 TI - Fatty acid transport protein-2 inhibitor Grassofermata/CB5 protects cells against lipid accumulation and toxicity. AB - The inhibition of the fatty acid uptake into non-adipose tissues provides an attractive target for prevention of lipotoxicity leading to obesity-associated non-alcoholic fatty liver disease and type 2 diabetes. Fatty acid transport proteins (FATPs) are bifunctional proteins involved in the uptake and activation of fatty acids by esterification with coenzyme A. Here we characterize Grassofermata/CB5, previously identified as a fatty acid uptake inhibitor directed against HsFATP2. The compound was effective in inhibiting the uptake of fatty acids in the low micro-molar range (IC50 8-11 MUM) and prevented palmitate mediated lipid accumulation and cell death in cell lines that are models for intestines, liver, muscle and pancreas. In adipocytes, uptake inhibition was less effective (IC50 58 MUM). Inhibition was specific for long chain fatty acids and was ineffective toward medium chain fatty acids, which are transported by diffusion. Kinetic analysis of Grassofermata-dependent FA transport inhibition verified a non-competitive mechanism. By comparison with Grassofermata, several atypical antipsychotic drugs previously implicated as inhibitors of FA uptake were ineffectual. In mice Grassofermata decreased absorption of (13)C-oleate demonstrating its potential as a therapeutic agent. PMID- 26284976 TI - Post-mortem imaging compared with autopsy in trauma victims--A systematic review. AB - BACKGROUND: Post-mortem imaging or virtual autopsy is a rapidly advancing field of post-mortem investigations of trauma victims. In this review we evaluate the feasibility of complementation or replacement of conventional autopsy by post mortem imaging in trauma victims. MATERIALS AND METHODS: A systematic review was performed in compliance with the PRISMA guidelines. MEDLINE, Embase and Cochrane databases were systematically searched for studies published between January 2008 and January 2014, in which post-mortem imaging was compared to conventional autopsy in trauma victims. Studies were included when two or more trauma victims were investigated. RESULTS: Twenty-six studies were included, with a total number of 563 trauma victims. Post-mortem computer tomography (PMCT) was performed in 22 studies, post-mortem magnetic resonance imaging (PMMRI) in five studies and conventional radiography in two studies. PMCT and PMMRI both demonstrate moderate to high-grade injuries and cause of death accurately. PMCT is more sensitive than conventional autopsy or PMMRI in detecting skeletal injuries. For detecting minor organ and soft tissue injuries, autopsy remains superior to imaging. Aortic injuries are missed frequently by PMCT and PMMRI and form their main limitation. CONCLUSION: PMCT should be considered as an essential supplement to conventional autopsy in trauma victims since it detects many additional injuries. Despite some major limitations, PMCT could be used as an alternative for conventional autopsy in situations where conventional autopsy is rejected or unavailable. PMID- 26284977 TI - Rigor mortis at the myocardium investigated by post-mortem magnetic resonance imaging. AB - INTRODUCTION: Post-mortem cardiac MR exams present with different contraction appearances of the left ventricle in cardiac short axis images. It was hypothesized that the grade of post-mortem contraction may be related to the post mortem interval (PMI) or cause of death and a phenomenon caused by internal rigor mortis that may give further insights in the circumstances of death. METHOD AND MATERIALS: The cardiac contraction grade was investigated in 71 post-mortem cardiac MR exams (mean age at death 52 y, range 12-89 y; 48 males, 23 females). In cardiac short axis images the left ventricular lumen volume as well as the left ventricular myocardial volume were assessed by manual segmentation. The quotient of both (LVQ) represents the grade of myocardial contraction. LVQ was correlated to the PMI, sex, age, cardiac weight, body mass and height, cause of death and pericardial tamponade when present. In cardiac causes of death a separate correlation was investigated for acute myocardial infarction cases and arrhythmic deaths. RESULTS: LVQ values ranged from 1.99 (maximum dilatation) to 42.91 (maximum contraction) with a mean of 15.13. LVQ decreased slightly with increasing PMI, however without significant correlation. Pericardial tamponade positively correlated with higher LVQ values. Variables such as sex, age, body mass and height, cardiac weight and cause of death did not correlate with LVQ values. There was no difference in LVQ values for myocardial infarction without tamponade and arrhythmic deaths. CONCLUSION: Based on the observation in our investigated cases, the phenomenon of post-mortem myocardial contraction cannot be explained by the influence of the investigated variables, except for pericardial tamponade cases. Further research addressing post-mortem myocardial contraction has to focus on other, less obvious factors, which may influence the early post-mortem phase too. PMID- 26284978 TI - Flemingin-Type Prenylated Chalcones from the Sarawak Rainforest Plant Desmodium congestum. AB - In an ongoing program to identify new anti-infective leads, an extract derived from whole plant material of Desmodium congestum collected in the Sarawak rainforest was found to have anti-MRSA activity. Bioassay-guided isolation led to the isolation of two new prenylated chalcones, 5'-O-methyl-3-hydroxyflemingin A (1) and 5'-O-methylflemingin C (2), which were closely related to the flemingins previously isolated from various Flemingia species. Chalcones 1 and 2, which were determined to be 4:6 enantiomeric mixtures by chiral HPLC, exhibited moderate activity against a panel of Gram-positive bacteria and were also cytotoxic to the HEK293 human embryonic kidney cell line. PMID- 26284980 TI - Generation of human iPSC line GRX-MCiPS4F-A2 from adult peripheral blood mononuclear cells (PBMCs) with Spanish genetic background. AB - We have generated iPSCs from peripheral blood mononuclear cells (PBMCs) of a healthy man using heat sensitive and non-integrative Sendai virus containing Sox2, Oct3/4, c-Myc and Klf4. Human GRX-MCiPS4F-A2 cell line was established and characterized through this study. PMID- 26284979 TI - hVGAT-mCherry: A novel molecular tool for analysis of GABAergic neurons derived from human pluripotent stem cells. AB - BACKGROUND: GABAergic synaptic transmission is known to play a critical role in the assembly of neuronal circuits during development and is responsible for maintaining the balance between excitatory and inhibitory signaling in the brain during maturation into adulthood. Importantly, defects in GABAergic neuronal function and signaling have been linked to a number of neurological diseases, including autism spectrum disorders, schizophrenia, and epilepsy. With patient specific induced pluripotent stem cell (iPSC)-based models of neurological disease, it is now possible to investigate the disease mechanisms that underlie deficits in GABAergic function in affected human neurons. To that end, tools that enable the labeling and purification of viable GABAergic neurons from human pluripotent stem cells would be of great value. RESULTS: To address the need for tools that facilitate the identification and isolation of viable GABAergic neurons from the in vitro differentiation of iPSC lines, a cell type-specific promoter-driven fluorescent reporter construct was developed that utilizes the human vesicular GABA transporter (hVGAT) promoter to drive the expression of mCherry specifically in VGAT-expressing neurons. The transduction of iPSC-derived forebrain neuronal cultures with the hVGAT promoter-mCherry lentiviral reporter construct specifically labeled GABAergic neurons. Immunocytochemical analysis of hVGAT-mCherry expression cells showed significant co-labeling with the GABAergic neuronal markers for endogenous VGAT, GABA, and GAD67. Expression of mCherry from the VGAT promoter showed expression in several cortical interneuron subtypes to similar levels. In addition, an effective and reproducible protocol was developed to facilitate the fluorescent activated cell sorting (FACS)-mediated purification of high yields of viable VGAT-positive cells. CONCLUSIONS: These studies demonstrate the utility of the hVGAT-mCherry reporter construct as an effective tool for studying GABAergic neurons differentiated in vitro from human pluripotent stem cells. This approach could provide a means of obtaining large quantities of viable GABAergic neurons derived from disease-specific hiPSCs that could be used for functional assays or high-throughput screening of small molecule libraries. PMID- 26284981 TI - Controlled Release of Salicylic Acid from Biodegradable Cross-Linked Polyesters. AB - The purpose of this work was to develop a family of cross-linked poly(xylitol adipate salicylate)s with a wide range of tunable release properties for delivering pharmacologically active salicylic acid. The synthesis parameters and release conditions were varied to modulate polyester properties and to understand the mechanism of release. Varying release rates were obtained upon longer curing (35% in the noncured polymer to 10% in the cured polymer in 7 days). Differential salicylic acid loading led to the synthesis of polymers with variable cross linking and the release could be tuned (100% release for the lowest loading to 30% in the highest loading). Controlled release was monitored by changing various factors, and the release profiles were dependent on the stoichiometric composition, pH, curing time, and presence of enzyme. The polymer released a combination of salicylic acid and disalicylic acid, and the released products were found to be nontoxic. Minimal hemolysis and platelet activation indicated good blood compatibility. These polymers qualify as "bioactive" and "resorbable" and can, therefore, find applications as immunomodulatory resorbable biomaterials with tunable release properties. PMID- 26284982 TI - Copper-Catalyzed Diazo Cross-/Homo-Coupling toward Tetrasubstituted Olefins and Applications on the Synthesis of Maleimide Derivatives. AB - A challenging selective intermolecular cross-coupling and homocoupling of aryl aryl or aryl-alkyl diazo compounds has been accomplished via a copper system, which afforded tetrasubstituted olefins in moderate to high yields with good to excellent Z-selectivity. This novel methodology enables rapid synthesis of tetrasubstituted olefins, which would find broad application in accessing maleimide libraries of nature products and bioactive small molecules. PMID- 26284983 TI - Effect of Practicing Soccer Juggling With Different Sized Balls Upon Performance, Retention, and Transfer to Ball Reception. AB - The aim of this study was to investigate if making the skill acquisition phase more difficult or easier would enhance performance in soccer juggling, and if this practice has a positive intertask transfer effect to ball reception performance. Twenty-two adolescent soccer players were tested in juggling a soccer ball and in the control of an approaching ball at a pre, post and retention test. The participants were randomly divided in a small ball size and bigger ball size training group that both trained four times per week for 6 weeks. At the post and retention test both groups enhanced performance in soccer juggling test with no difference between groups and no increase in ball reception performance at these tests. It was concluded that about intra task transfer and retention of soccer juggling skills, it does not matter if you increase (small balls) or decrease the difficulty (larger balls) when using the same amount of practice time within the skill acquisition phase in soccer juggling. In addition that for ball juggling and ball reception (inter task) these two tasks differ too much in afferent information and movement characteristics that no positive transfer between these two skills no positive intertask transfer can be expected. PMID- 26284984 TI - Plasticized Polymer Composite Single-Ion Conductors for Lithium Batteries. AB - Lithium bis(trifluoromethane) sulfonamide (TFSI) is a promising electrolyte salt in lithium batteries, due to its good conductivity and high dissociation between the lithium cation and its anion. By tethering N-pentane trifluoromethane sulfonamide (C5NHTf), a TFSI analogue molecule, onto the surface of silica nanoparticle as a monolayer coverage should increase the Li(+) transference number to unity since anions bound to particles have reduced mobilities. Silica polymer composite has better mechanical property than that of the pure PEO. Analogously trifluoromethane sulfonic aminoethyl methacrylate (TfMA), a TFSI analogue vinyl monomer, was polymerized on silica nanoparticle surface as a multilayer coverage. Anchored polyelectrolytes to particle surfaces offer multiple sites for anions, and in principle the carrier concentration would increase arbitrarily and approach the carrier concentration of the bulk polyelectrolyte. Monolayer grafted nanoparticles have a lithium content of 1.2 * 10(-3) g Li/g, and multilayer grafted nanoparticles have a lithium content over an order higher at 2 * 10(-2) g Li/g. Electrolytes made from monolayer grafted particles exhibit a weak conductivity dependence on temperature, exhibiting an ionic conductivity in the range of 10(-6) S/cm when temperatures increase to 80 degrees C. While electrolytes made from multilayer grafted particles show a steep increase in conductivity with temperature with an ionic conductivity increase to 3 * 10(-5) S/cm at 80 degrees C, with an O/Li ratio of 32. PMID- 26284985 TI - Evaluation of Toxicity Ranking for Metal Oxide Nanoparticles via an in Vitro Dosimetry Model. AB - It has been argued that in vitro toxicity testing of engineered nanoparticles (NPs) should consider delivered dose (i.e., NP mass settled per suspension volume) rather than relying exclusively on administered dose (initial NP mass concentration). Delivered dose calculations require quantification of NP sedimentation in tissue cell culture media, taking into consideration fundamental suspension properties. In this article, we calculate delivered dose using a first principles "particles in a box" sedimentation model, which accounts for the particle size distribution, fractal dimension, and permeability of agglomerated NPs. The sedimentation model was evaluated against external and our own experimental sedimentation data for metal oxide NPs. We then utilized the model to construct delivered dose-response analysis for a library of metal oxide NPs (previously used for hazard ranking and prediction making) in different cell culture media. Hierarchical hazard ranking of the seven (out of 24) toxic metal oxide NPs in our library, using EC50 calculated on the basis of delivered dose, did not measurably differ from our ranking based on administered dose. In contrast, simplified sedimentation calculations based on the assumption of impermeable NP agglomerates of a single average size significantly underestimated the settled NPs' mass, resulting in misinterpretation of toxicity ranking. It is acknowledged that in vitro dose-response outcomes are likely to be shaped by complex toxicodynamics, which include NP/cellular association, triggering of dynamic cell response pathways involved in NP uptake, and multiple physicochemical parameters that influence NP sedimentation and internalization. PMID- 26284986 TI - Updated methods for assessing the impacts of nearby gas drilling and production on neighborhood air quality and human health. AB - An explosive growth in natural gas production within the last decade has fueled concern over the public health impacts of air pollutant emissions from oil and gas sites in the Barnett and Eagle Ford shale regions of Texas. Commonly acknowledged sources of uncertainty are the lack of sustained monitoring of ambient concentrations of pollutants associated with gas mining, poor quantification of their emissions, and inability to correlate health symptoms with specific emission events. These uncertainties are best addressed not by conventional monitoring and modeling technology, but by increasingly available advanced techniques for real-time mobile monitoring, microscale modeling and source attribution, and real-time broadcasting of air quality and human health data over the World Wide Web. The combination of contemporary scientific and social media approaches can be used to develop a strategy to detect and quantify emission events from oil and gas facilities, alert nearby residents of these events, and collect associated human health data, all in real time or near-real time. The various technical elements of this strategy are demonstrated based on the results of past, current, and planned future monitoring studies in the Barnett and Eagle Ford shale regions. IMPLICATIONS: Resources should not be invested in expanding the conventional air quality monitoring network in the vicinity of oil and gas exploration and production sites. Rather, more contemporary monitoring and data analysis techniques should take the place of older methods to better protect the health of nearby residents and maintain the integrity of the surrounding environment. PMID- 26284988 TI - Identification and analysis of retrogenes in the East Asian nematode Caenorhabditis sp. 5 genome. AB - Retroposition, a molecular mechanism generating new genes, helps the formation of retrogenes and new functions, contributing to the evolution of genomes. The completed genome sequence of Caenorhabditis sp. 5 presents an excellent opportunity to identify retrogenes within C. sp. 5. We identified a total of 43 retrogenes and their corresponding chimeric genes. Among these, 29 were found to be intact retrogenes and 14 to be retropseudogenes. Unexpectedly, a high number of retrogenes appear to be functional and possibly involved in catalysis. Also, the proportion of the retrogenes forming chimeric structure is the highest among Caenorhabditis nematodes. In addition, the Ks distribution shows that C. sp. 5 has more retrogenes with high Ks, which may explain the high functionality of them among Caenorhabditis species. Our study will be helpful in the understanding of the functional and evolutionary impact of retroposition on C. sp. 5 genome. PMID- 26284989 TI - Oxygen Conditioning at High Altitude. PMID- 26284990 TI - Physical Activity, Exercise, and Mammalian Testis Function: Emerging Preclinical Protein Biomarker and Integrative Biology Insights. AB - Exercise and physical activity have long been recognized for health promotion and to delay the onset of many pathological situations such as diabetes and cancers. Still, there appears to be an upper limit on the beneficial health effects regarding intensity and frequency of exercise training. In humans, the effect of exercise training in the male reproductive system has been studied mainly through the analysis of semen quality parameters, with inconsistent results. Less is known on molecular biomarkers of exercise-related changes in testis at the protein/proteome level. This review offers an in-depth analysis on the small scale protein studies available primarily from the preclinical studies and interprets their functional impact on the reproductive health with a view to humans. In all, exercise training in preclinical models seems to negatively modulate, in the course of health, critical functions that directly affect spermatogenesis, such as testosterone biosynthesis, energy supply, and antioxidant system components. Exercise training induces apoptosis, leading to the impairment of spermatogenesis and, consequently, to male infertility. In pathological conditions, an improvement in the testicular functions is observed by increases in steroidogenic enzymes and antioxidant defenses, and reductions in activity of inflammatory pathways. Importantly, the mechanisms by which exercise training modulates the reproductive function are far from being fully understood. The analyses of the testis proteome in varying exercise conditions would inform the molecular mechanisms involved and identify putative theranostics opportunities. Such future research is a cornerstone for health promotion in the pursuit of reproductive health informed by omics systems sciences. PMID- 26284991 TI - Oscillations or Synchrony? Disruption of Neural Synchrony despite Enhanced Gamma Oscillations in a Model of Disrupted Perceptual Coherence. AB - It has been hypothesized that neural synchrony underlies perceptual coherence. The hypothesis of loss of central perceptual coherence has been proposed to be at the origin of abnormal cognition in autism spectrum disorders and Williams syndrome, a neurodevelopmental disorder linked with autism, and a clearcut model for impaired central coherence. We took advantage of this model of impaired holistic processing to test the hypothesis that loss of neural synchrony plays a separable role in visual integration using EEG and a set of experimental tasks requiring coherent integration of local elements leading to 3-D face perception. A profound reorganization of brain activity was identified. Neural synchrony was reduced across stimulus conditions, and this was associated with increased amplitude modulation at 25-45 Hz. This combination of a dramatic loss of synchrony despite increased oscillatory activity is strong evidence that synchrony underlies central coherence. This is the first time, to our knowledge, that dissociation between amplitude and synchrony is reported in a human model of impaired perceptual coherence, suggesting that loss of phase coherence is more directly related to disruption of holistic perception. PMID- 26284992 TI - Steady-state BOLD Response to Higher-order Cognition Modulates Low-Frequency Neural Oscillations. AB - Steady-state responses (SSRs) reflect the synchronous neural oscillations evoked by noninvasive and consistently repeated stimuli at the fundamental or harmonic frequencies. The steady-state evoked potentials (SSEPs; the representative form of the SSRs) have been widely used in the cognitive and clinical neurosciences and brain-computer interface research. However, the steady-state evoked potentials have limitations in examining high-frequency neural oscillations and basic cognition. In addition, synchronous neural oscillations in the low frequency range (<1 Hz) and in higher-order cognition have received a little attention. Therefore, we examined the SSRs in the low frequency range using a new index, the steady-state BOLD responses (SSBRs) evoked by semantic stimuli. Our results revealed that the significant SSBRs were induced at the fundamental frequency of stimuli and the first harmonic in task-related regions, suggesting the enhanced variability of neural oscillations entrained by exogenous stimuli. The SSBRs were independent of neurovascular coupling and characterized by sensorimotor bias, an indication of regional-dependent neuroplasticity. Furthermore, the amplitude of SSBRs may predict behavioral performance and show the psychophysiological relevance. Our findings provide valuable insights into the understanding of the SSRs evoked by higher-order cognition and how the SSRs modulate low-frequency neural oscillations. PMID- 26284993 TI - Electrophysiological and Kinematic Correlates of Communicative Intent in the Planning and Production of Pointing Gestures and Speech. AB - In everyday human communication, we often express our communicative intentions by manually pointing out referents in the material world around us to an addressee, often in tight synchronization with referential speech. This study investigated whether and how the kinematic form of index finger pointing gestures is shaped by the gesturer's communicative intentions and how this is modulated by the presence of concurrently produced speech. Furthermore, we explored the neural mechanisms underpinning the planning of communicative pointing gestures and speech. Two experiments were carried out in which participants pointed at referents for an addressee while the informativeness of their gestures and speech was varied. Kinematic and electrophysiological data were recorded online. It was found that participants prolonged the duration of the stroke and poststroke hold phase of their gesture to be more communicative, in particular when the gesture was carrying the main informational burden in their multimodal utterance. Frontal and P300 effects in the ERPs suggested the importance of intentional and modality independent attentional mechanisms during the planning phase of informative pointing gestures. These findings contribute to a better understanding of the complex interplay between action, attention, intention, and language in the production of pointing gestures, a communicative act core to human interaction. PMID- 26284994 TI - Competition between Mutually Exclusive Object States in Event Comprehension. AB - Successful language comprehension requires one to correctly match symbols in an utterance to referents in the world, but the rampant ambiguity present in that mapping poses a challenge. Sometimes the ambiguity lies in which of two (or more) types of things in the world are under discussion (i.e., lexical ambiguity); however, even a word with a single sense can have an ambiguous referent. This ambiguity occurs when an object can exist in multiple states. Here, we consider two cases in which the presence of multiple object states may render a single sense word ambiguous. In the first case, one must disambiguate between two states of a single object token in a short discourse. In the second case, the discourse establishes two different tokens of the object category. Both cases involve multiple object states: These states are mutually exclusive in the first case, whereas in the second case, these states can logically exist at the same time. We use fMRI to contrast same-token and different-token discourses, using responses in left posterior ventrolateral prefrontal cortex (pVLPFC) as an indicator of conflict. Because the left pVLPFC is sensitive to competition between multiple, incompatible representations, we predicted that state ambiguity should engender conflict only when those states are mutually exclusive. Indeed, we find evidence of conflict in same-token, but not different-token, discourses. Our data support a theory of left pVLPFC function in which general conflict resolution mechanisms are engaged to select between multiple incompatible representations that arise in many kinds of ambiguity present in language. PMID- 26284995 TI - Musical Meter Modulates the Allocation of Attention across Time. AB - Dynamic attending theory predicts that attention is allocated hierarchically across time during processing of hierarchical rhythmic structures such as musical meter. ERP research demonstrates that attention to a moment in time modulates early auditory processing as evidenced by the amplitude of the first negative peak (N1) approximately 100 msec after sound onset. ERPs elicited by tones presented at times of high and low metric strength in short melodies were compared to test the hypothesis that hierarchically structured rhythms direct attention in a manner that modulates early perceptual processing. A more negative N1 was observed for metrically strong beats compared with metrically weak beats; this result provides electrophysiological evidence that hierarchical rhythms direct attention to metrically strong times during engaged listening. The N1 effect was observed only on fast tempo trials, suggesting that listeners more consistently invoke selective processing based on hierarchical rhythms when sounds are presented rapidly. The N1 effect was not modulated by musical expertise, indicating that the allocation of attention to metrically strong times is not dependent on extensive training. Additionally, changes in P2 amplitude and a late negativity were associated with metric strength under some conditions, indicating that multiple cognitive processes are associated with metric perception. PMID- 26284996 TI - Effects of Transcranial Direct Current Stimulation over Left Dorsolateral pFC on the Attentional Blink Depend on Individual Baseline Performance. AB - Selection mechanisms that dynamically gate only relevant perceptual information for further processing and sustained representation in working memory are critical for goal-directed behavior. We examined whether this gating process can be modulated by anodal transcranial direct current stimulation (tDCS) over left dorsolateral pFC (DLPFC)--a region known to play a key role in working memory and conscious access. Specifically, we examined the effects of tDCS on the magnitude of the so-called "attentional blink" (AB), a deficit in identifying the second of two targets presented in rapid succession. Thirty-four participants performed a standard AB task before (baseline), during, and after 20 min of 1-mA anodal and cathodal tDCS in two separate sessions. On the basis of previous reports linking individual differences in AB magnitude to individual differences in DLPFC activity and on suggestions that effects of tDCS depend on baseline brain activity levels, we hypothesized that anodal tDCS over left DLPFC would modulate the magnitude of the AB as a function of individual baseline AB magnitude. Indeed, individual differences analyses revealed that anodal tDCS decreased the AB in participants with a large baseline AB but increased the AB in participants with a small baseline AB. This effect was only observed during (but not after) stimulation, was not found for cathodal tDCS, and could not be explained by regression to the mean. Notably, the effects of tDCS were not apparent at the group level, highlighting the importance of taking individual variability in performance into account when evaluating the effectiveness of tDCS. These findings support the idea that left DLPFC plays a critical role in the AB and in conscious access more generally. They are also in line with the notion that there is an optimal level of prefrontal activity for cognitive function, with both too little and too much activity hurting performance. PMID- 26284998 TI - Quantification of PEG-maleimide ligands and coupling efficiencies on nanoparticles with Ellman's reagent. AB - The surface modification of nanometer- and micrometer-sized particles and planar substrates with polyethylene glycol (PEG) ligands of varying length is a very common strategy to tune the hydrophilicity and biocompatibility of such materials, minimize unspecific interactions, improve biofunctionalization efficiencies, and enhance blood circulation times. Nevertheless, simple methods for the quantification of PEG ligands are comparatively rare. Here, we present a new concept for the quantification of PEG ligands for maleimide-functionalized PEG molecules and the determination of PEG coupling efficiencies, exploiting the quantitative reaction of maleimide with l-cysteine, and the subsequent determination of the unreacted thiol with the photometric Ellman's test. This is shown for heterobifunctional PEG spacers of varying length and amino functionalized polystyrene nanoparticles (PS NP) without and with differently charged encoding dyes. The reaction of l-cysteine with the Ellman's reagent was monitored photometrically and with electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS) to derive the reaction mechanism and to obtain the stoichiometry factor for l-cysteine quantification. Mass balances and quantification of l-cysteine via its sulfur concentration using elemental analysis and inductively coupled plasma mass spectrometry (ICP-MS) confirmed the accuracy and reliability of this approach that can be extended to other surface groups and ligands. PMID- 26284999 TI - Social models of HIV risk among young adults in Lesotho. AB - Extensive research over the past 30 years has revealed that individual and social determinants impact HIV risk. Even so, prevention efforts focus primarily on individual behaviour change, with little recognition of the dynamic interplay of individual and social environment factors that further exacerbate risk engagement. Drawing on long-term research with young adults in Lesotho, I examine how social environment factors contribute to HIV risk. During preliminary ethnographic analysis, I developed novel scales to measure social control, adoption of modernity, and HIV knowledge. In survey research, I examined the effects of individual characteristics (i.e., socioeconomic status, HIV knowledge, adoption of modernity) and social environment (i.e., social control) on HIV risk behaviours. In addition, I measured the impact of altered environments by taking advantage of an existing situation whereby young adults attending a national college are assigned to either a main campus in a metropolitan setting or a satellite campus in a remote setting, irrespective of the environment in which they were socialised as youth. This arbitrary assignment process generates four distinct groups of young adults with altered or constant environments. Regression models show that lower levels of perceived social control and greater adoption of modernity are associated with HIV risk, controlling for other factors. The impact of social control and modernity varies with environment dynamics. PMID- 26285000 TI - Skeletal muscle sodium channelopathies. AB - PURPOSE OF REVIEW: This is an update on skeletal muscle sodium channelopathies since knowledge in the field have dramatically increased in the past years. RECENT FINDING: The relationship between two phenotypes and SCN4A has been confirmed with additional cases that remain extremely rare: severe neonatal episodic laryngospasm mimicking encephalopathy, which should be actively searched for since patients respond well to sodium channel blockers; congenital myasthenic syndromes, which have the particularity to be the first recessive Nav1.4 channelopathy. Deep DNA sequencing suggests the contribution of other ion channels in the clinical expressivity of sodium channelopathies, which may be one of the factors modulating the latter. The increased knowledge of channel molecular structure, the quantity of sodium channel blockers, and the availability of preclinical models would permit a most personalized choice of medication for patients suffering from these debilitating neuromuscular diseases. SUMMARY: Advances in the understanding of the molecular structure of voltage gated sodium channels, as well as availability of preclinical models, would lead to improved medical care of patients suffering from skeletal muscle, as well as other sodium channelopathies. PMID- 26285001 TI - A novel fluorescent retrograde neural tracer: cholera toxin B conjugated carbon dots. AB - The retrograde neuroanatomical tracing method is a key technique to study the complex interconnections of the nervous system. Traditional tracers have several drawbacks, including time-consuming immunohistochemical or immunofluorescent staining procedures, rapid fluorescence quenching and low fluorescence intensity. Carbon dots (CDs) have been widely used as a fluorescent bio-probe due to their ultrasmall size, excellent optical properties, chemical stability, biocompatibility and low toxicity. Herein, we develop a novel fluorescent neural tracer: cholera toxin B-carbon dot conjugates (CTB-CDs). It can be taken up and retrogradely transported by neurons in the peripheral nervous system of rats. Our results show that CTB-CDs possess high photoluminescence intensity, good optical stability, a long shelf-life and non-toxicity. Tracing with CTB-CDs is a direct and more economical way of performing retrograde labelling experiments. Therefore, CTB-CDs are reliable fluorescent retrograde tracers. PMID- 26285002 TI - Combined pressure and cosolvent effects on enzyme activity - a high-pressure stopped-flow kinetic study on alpha-chymotrypsin. AB - We investigated the combined effects of cosolvents and pressure on the hydrolysis of a model peptide catalysed by alpha-chymotrypsin. The enzymatic activity was measured in the pressure range from 0.1 to 200 MPa using a high-pressure stopped flow systems with 10 ms time resolution. A kosmotropic (trimethalymine-N-oxide, TMAO) and chaotropic (urea) cosolvent and mixtures thereof were used as cosolvents. High pressure enhances the hydrolysis rate as a consequence of a negative activation volume, DeltaV(#), which, depending on the cosolvent system, amounts to -2 to -4 mL mol(-1). A more negative activation volume can be explained by a smaller compression of the ES complex relative to the transition state. Kinetic constants, such as kcat and the Michaelis constant KM, were determined for all solution conditions as a function of pressure. With increasing pressure, kcat increases by about 35% and its pressure dependence by a factor of 1.9 upon addition of 2 M urea, whereas 1 M TMAO has no significant effect on kcat and its pressure dependence. Similarly, KM increases upon addition of urea 6 fold. Addition of TMAO compensates the urea-effect on kcat and KM to some extent. The maximum rate of the enzymatic reaction increases with increasing pressure in all solutions except in the TMAO : urea 1 : 2 mixture, where, remarkably, pressure is found to have no effect on the rate of the enzymatic reaction anymore. Our data clearly show that compatible solutes can easily override deleterious effects of harsh environmental conditions, such as high hydrostatic pressures in the 100 MPa range, which is the maximum pressure encountered in the deep biosphere on Earth. PMID- 26285003 TI - A Collaborative Paradigm for Improving Management of Sleep Disorders in Primary Care: A Randomized Clinical Trial. AB - OBJECTIVES: To test a collaborative care model for interfacing sleep specialists with primary care providers to enhance patients' sleep disorders management. METHODS: This study used a randomized, parallel group, clinical intervention trial design. A total of 137 adult (29 women) VA outpatients with sleep complaints were enrolled and randomly assigned to (1) an intervention (INT) consisting of a one-time consultation with a sleep specialist who provided diagnostic feedback and treatment recommendations to the patient and the patient's primary care provider; or (2) a control condition consisting of their usual primary care (UPC). Provider-focused outcomes included rates of adherence to recommended diagnostic procedures and sleep-focused interventions. Patient focused outcomes included measures taken from sleep diaries and actigraphy; Pittsburgh Sleep Quality Index (PSQI) scores; and self-report measures of sleepiness, fatigue, mood, quality of life, and satisfaction with health care. RESULTS: The proportions of provider-initiated sleep-focused interventions were significantly higher in the INT group than in the UPC group for polysomnography referrals (49% versus 6%; P < 0.001) and mental health clinic referrals (19% versus 6%; P = 0.02). At the 10-mo follow up, INT recipients showed greater estimated mean reductions in diary total wake time (-17.0 min; 95% confidence interval [CI]: -30.9, -3.1; P = 0.02) and greater increases in sleep efficiency (+3.7%; 95% CI: 0.8, 6.5; P = 0.01) than did UPC participants. A greater proportion of the INT group showed >= 1 standard deviation decline on the PSQI from baseline to the 10-mo follow-up (41% versus 21%; P = 0.02). Moreover, 69% of the INT group had normal (<= 10) Epworth Sleepiness Scale scores at the 10-mo follow-up, whereas only 50% of the UPC group fell below this clinical cutoff (P = 0.03). CONCLUSIONS: A one-time sleep consultation significantly increased healthcare providers' attention to sleep problems and resulted in benefits to patients' sleep/wake symptoms. CLINICAL TRIALS REGISTRATION: This study is registered with clinicaltrials.gov with identifier # NCT00390572. PMID- 26285004 TI - Maturational Patterns of Sigma Frequency Power Across Childhood and Adolescence: A Longitudinal Study. AB - STUDY OBJECTIVES: To further evaluate adolescent brain maturation by determining the longitudinal trajectories of nonrapid eye movement (NREM) sigma (11-15 Hz) power across childhood-adolescence. METHODS: The maturational trend for sigma (11 15 Hz) power was evaluated in an accelerated longitudinal study of three overlapping age cohorts (n = 92) covering ages 6 to 18 y. Semiannually, sleep electroencephalography (EEG) was recorded from participants sleeping at home in their normal sleep environment while keeping their current school night schedules. RESULTS: Sigma frequencies became faster with age. The frequency of the 11-15 Hz spectral peak increased linearly. Sigma frequency power (SFP) declined with age, but its trajectory was complex (cubic). Power in a group of low sigma subfrequencies declined with age. Power in a group of high sigma frequencies increased with age. Power in subfrequencies within 11-15 Hz also showed different trends across the night, with lower frequencies increasing across NREM periods and higher frequencies decreasing across NREM periods. The upper and lower boundaries for the sigma frequencies that changed across NREMPs shifted upward with age. CONCLUSIONS: We hypothesize that these maturational brain changes result from synaptic elimination which decreases sleep depth and streamlines circuits. SFP displays a maturational trajectory different from both delta and theta power. Theories on the function of sigma must be reconciled with its maturational trajectory. These findings further demonstrate the value of sleep EEG for studying noninvasively the complex developmental brain changes of adolescence. PMID- 26284997 TI - Molecular cancer prevention: Current status and future directions. AB - The heterogeneity and complexity of advanced cancers strongly support the rationale for an enhanced focus on molecular prevention as a priority strategy to reduce the burden of cancer. Molecular prevention encompasses traditional chemopreventive agents as well as vaccinations and therapeutic approaches to cancer-predisposing conditions. Despite challenges to the field, we now have refined insights into cancer etiology and early pathogenesis; successful risk assessment and new risk models; agents with broad preventive efficacy (eg, aspirin) in common chronic diseases, including cancer; and a successful track record of more than 10 agents approved by the US Food and Drug Administration for the treatment of precancerous lesions or cancer risk reduction. The development of molecular preventive agents does not differ significantly from the development of therapies for advanced cancers, yet it has unique challenges and special considerations given that it most often involves healthy or asymptomatic individuals. Agents, biomarkers, cohorts, overall design, and endpoints are key determinants of molecular preventive trials, as with therapeutic trials, although distinctions exist for each within the preventive setting. Progress in the development and evolution of molecular preventive agents has been steadier in some organ systems, such as breast and skin, than in others. In order for molecular prevention to be fully realized as an effective strategy, several challenges to the field must be addressed. Here, the authors provide a brief overview of the context for and special considerations of molecular prevention along with a discussion of the results from major randomized controlled trials. PMID- 26285005 TI - Global and Regional Brain Non-Gaussian Diffusion Changes in Newly Diagnosed Patients with Obstructive Sleep Apnea. AB - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) patients show brain structural injury and functional deficits in autonomic, affective, and cognitive regulatory sites, as revealed by mean diffusivity (MD) and other imaging procedures. The time course and nature of gray and white matter injury can be revealed in more detail with mean kurtosis (MK) procedures, which can differentiate acute from chronic injury, and better show extent of damage over MD procedures. Our objective was to examine global and regional MK changes in newly diagnosed OSA, relative to control subjects. METHODS: Two diffusion kurtosis image series were collected from 22 recently-diagnosed, treatment-naive OSA and 26 control subjects using a 3.0-Tesla MRI scanner. MK maps were generated, normalized to a common space, smoothed, and compared voxel-by-voxel between groups using analysis of covariance (covariates; age, sex). RESULTS: No age or sex differences appeared, but body mass index, sleep, neuropsychologic, and cognitive scores significantly differed between groups. MK values were significantly increased globally in OSA over controls, and in multiple localized sites, including the basal forebrain, extending to the hypothalamus, hippocampus, thalamus, insular cortices, basal ganglia, limbic regions, cerebellar areas, parietal cortices, ventral temporal lobe, ventrolateral medulla, and midline pons. Multiple sites, including the insular cortices, ventrolateral medulla, and midline pons showed more injury over previously identified damage with MD procedures, with damage often lateralized. CONCLUSIONS: Global mean kurtosis values are significantly increased in obstructive sleep apnea (OSA), suggesting acute tissue injury, and these changes are principally localized in critical sites mediating deficient functions in the condition. The mechanisms for injury likely include altered perfusion and hypoxemia-induced processes, leading to acute tissue changes in recently diagnosed OSA. PMID- 26285006 TI - Sleep-Dependent Potentiation in the Visual System Is at Odds with the Synaptic Homeostasis Hypothesis. AB - STUDY OBJECTIVES: Two commentaries recently published in SLEEP came to very different conclusions regarding how data from a mouse model of sleep-dependent neural plasticity (orientation-specific response potentiation; OSRP) fit with the synaptic homeostasis hypothesis (SHY). To assess whether SHY offers an explanatory mechanism for OSRP, we present new data on how cortical neuron firing rates are modulated as a function of novel sensory experience and subsequent sleep in this model system. METHODS: We carried out longitudinal extracellular recordings of single-neuron activity in the primary visual cortex across a period of novel visual experience and subsequent sleep or sleep deprivation. Spontaneous neuronal firing rates and visual responses were recorded from the same population of visual cortex neurons before control (blank screen) or novel (oriented grating) stimulus presentation, immediately after stimulus presentation, and after a period of subsequent ad lib sleep or sleep deprivation. RESULTS: Firing rate responses to visual stimuli were unchanged across waking experience, regardless of whether a blank screen or an oriented grating stimulus was presented. Firing rate responses to stimuli of the presented stimulus orientation were selectively enhanced across post-stimulus sleep, but these changes were blocked by sleep deprivation. Neuronal firing increased significantly across bouts of post-stimulus rapid eye movement (REM) sleep and slow wave sleep (SWS), but not across bouts of wake. CONCLUSIONS: The current data suggest that following novel visual experience, potentiation of a subset of V1 synapses occurs across periods of sleep. This finding cannot be explained parsimoniously by SHY. PMID- 26285007 TI - Sleep, Don't Sneeze: Longer Sleep Reduces the Risk of Catching a Cold. PMID- 26285008 TI - Altered Resting Cerebral Blood Flow in Obstructive Sleep Apnea: A Helpful Change or Not? PMID- 26285010 TI - How Different Are Our Perceptions of Equal-Tempered and Microtonal Intervals? A Behavioural and EEG Survey. AB - For listeners familiar with Western twelve-tone equal-tempered (12-TET) music, a novel microtonal tuning system is expected to present additional processing challenges. We aimed to determine whether this was the case, focusing on the extent to which our perceptions can be considered bottom-up (psychoacoustic and primarily perceptual) and top-down (dependent on familiarity and cognitive processing). We elicited both overt response ratings, and covert event-related potentials (ERPs), so as to compare subjective impressions of sounds with the neurophysiological processing of the acoustic signal. We hypothesised that microtonal intervals are perceived differently from 12-TET intervals, and that the responses of musicians (n = 10) and non-musicians (n = 10) are distinct. Two note chords were presented comprising 12-TET intervals (consonant and dissonant) or microtonal (quarter tone) intervals, and ERP, subjective roughness ratings, and liking ratings were recorded successively. Musical experience mediated the perception of differences between dissonant and microtone intervals, with non musicians giving similar ratings for each, and musicians preferring dissonant over the less commonly used microtonal intervals, rating them as less rough. ERP response amplitude was greater for consonant intervals than other intervals. Musical experience interacted with interval type, suggesting that musical expertise facilitates the sensory and perceptual discrimination of microtonal intervals from 12-TET intervals, and an increased ability to categorize such intervals. Non-musicians appear to have perceived microtonal intervals as instances of neighbouring 12-TET intervals. PMID- 26285009 TI - Sleep Duration and Area-Level Deprivation in Twins. AB - STUDY OBJECTIVES: We used quantitative genetic models to assess whether area level deprivation as indicated by the Singh Index predicts shorter sleep duration and modifies its underlying genetic and environmental contributions. METHODS: Participants were 4,218 adult twin pairs (2,377 monozygotic and 1,841 dizygotic) from the University of Washington Twin Registry. Participants self-reported habitual sleep duration. The Singh Index was determined by linking geocoding addresses to 17 indicators at the census-tract level using data from Census of Washington State and Census Tract Cartographic Boundary Files from 2000 and 2010. Data were analyzed using univariate and bivariate genetic decomposition and quantitative genetic interaction models that assessed A (additive genetics), C (common environment), and E (unique environment) main effects of the Singh Index on sleep duration and allowed the magnitude of residual ACE variance components in sleep duration to vary with the Index. RESULTS: The sample had a mean age of 38.2 y (standard deviation [SD] = 18), and was predominantly female (62%) and Caucasian (91%). Mean sleep duration was 7.38 h (SD = 1.20) and the mean Singh Index score was 0.00 (SD = 0.89). The heritability of sleep duration was 39% and the Singh Index was 12%. The uncontrolled phenotypic regression of sleep duration on the Singh Index showed a significant negative relationship between area-level deprivation and sleep length (b = -0.080, P < 0.001). Every 1 SD in Singh Index was associated with a ~4.5 min change in sleep duration. For the quasi-causal bivariate model, there was a significant main effect of E (b(0E) = -0.063; standard error [SE] = 0.30; P < 0.05). Residual variance components unique to sleep duration were significant for both A (b(0Au) = 0.734; SE = 0.020; P < 0.001) and E (b(0Eu) = 0.934; SE = 0.013; P < 0.001). CONCLUSIONS: Area-level deprivation has a quasi-causal association with sleep duration, with greater deprivation being related to shorter sleep. As area-level deprivation increases, unique genetic and nonshared environmental residual variance in sleep duration increases. PMID- 26285011 TI - Association of Genetic Polymorphisms in CDH1 and CTNNB1 with Breast Cancer Susceptibility and Patients' Prognosis among Chinese Han Women. AB - This study aims to investigate whether the germline variants in CDH1 and CTNNB1 would affect breast cancer susceptibility and patients' prognosis among Chinese Han women using a haplotype-based association analysis. We genotyped 12 haplotype tagging single nucleotide polymorphisms (htSNPs) in CDH1 and CTNNB1 among 1,160 BC cases and 1,336 age-matched cancer-free controls using the TaqMan(r) Genotyping Assay. For association analyses of germline variants with breast cancer susceptibility, the results showed that rs7200690, rs7198799, rs17715799, rs13689 and diplotype CGC/TGC (rs7200690 + rs12185157 + rs7198799) in CDH1 as well as rs2293303 in CTNNB1 were associated with increased breast cancer risk. In addition, the Generalized Multifactor Dimensionality Reduction (GMDR) and logistic regression analysis predicted an interaction on breast cancer risk between rs17715799 and rs13689 as well as rs13689 and menarche-FFTP (First Full Term Pregnancy) interval. For survival analyses, the results demonstrated that the minor allele homozygotes of rs13689 and haplotype TGC in CDH1 were linked with unfavorable event-free survival of breast cancer, whereas, rs4783689 of CDH1 showed the opposite effect under dominant model. Notably, the stratified analysis revealed that rs7186053 was associated with favorable event-free survival among patients with estrogen receptor (ER)-positive, progesterone receptor (PR) positive or lymph node metastasis negative patients. Moreover, rs7200690 and rs7198799 in CDH1 as well as rs4533622 in CTNNB1 were associated with worse event free survival among patients with clinical stage 0-I tumors. This study indicated that the genetic polymorphisms of CDH1 and CTNNB1 were associated with breast cancer susceptibility and patients' prognosis. PMID- 26285012 TI - A Stochastic Multiscale Model That Explains the Segregation of Axonal Microtubules and Neurofilaments in Neurological Diseases. AB - The organization of the axonal cytoskeleton is a key determinant of the normal function of an axon, which is a long thin projection of a neuron. Under normal conditions two axonal cytoskeletal polymers, microtubules and neurofilaments, align longitudinally in axons and are interspersed in axonal cross-sections. However, in many neurotoxic and neurodegenerative disorders, microtubules and neurofilaments segregate apart from each other, with microtubules and membranous organelles clustered centrally and neurofilaments displaced to the periphery. This striking segregation precedes the abnormal and excessive neurofilament accumulation in these diseases, which in turn leads to focal axonal swellings. While neurofilament accumulation suggests an impairment of neurofilament transport along axons, the underlying mechanism of their segregation from microtubules remains poorly understood for over 30 years. To address this question, we developed a stochastic multiscale model for the cross-sectional distribution of microtubules and neurofilaments in axons. The model describes microtubules, neurofilaments and organelles as interacting particles in a 2D cross-section, and is built upon molecular processes that occur on a time scale of seconds or shorter. It incorporates the longitudinal transport of neurofilaments and organelles through this domain by allowing stochastic arrival and departure of these cargoes, and integrates the dynamic interactions of these cargoes with microtubules mediated by molecular motors. Simulations of the model demonstrate that organelles can pull nearby microtubules together, and in the absence of neurofilament transport, this mechanism gradually segregates microtubules from neurofilaments on a time scale of hours, similar to that observed in toxic neuropathies. This suggests that the microtubule-neurofilament segregation can be a consequence of the selective impairment of neurofilament transport. The model generates the experimentally testable prediction that the rate and extent of segregation will be dependent on the sizes of the moving organelles as well as the density of their traffic. PMID- 26285013 TI - Deletion of RBPJK in Mesenchymal Stem Cells Enhances Osteogenic Activity by Up Regulation of BMP Signaling. AB - Recently we have demonstrated the importance of RBPjk-dependent Notch signaling in the regulation of mesenchymal stem cell (MSC) differentiation during skeletogenesis both in vivo and in vitro. Here we further performed RBPJK loss-of function experiments to demonstrate for the first time that RBPJK deficient MSC shows enhanced differentiation and osteogenesis acts via up-regulation of the BMP signaling. In the present study, we first compared the spontaneous and osteogenic differentiation in normal and recombination signal binding protein for immunoglobulin kappa J region (RBPJK) deficient human bone marrow-derived mesenchymal stem cells (MSCs). It was found that RBPJK highly expressed in fresh isolated MSCs and its expression was progressing down-regulated during spontaneous differentiation and even greater in osteogenic media inducted differentiation. Deletion of RBPJK in MSCs not only enhances cell spontaneous differentiation, but also significantly accelerates condition media inducted osteogenic differentiation by showing enhanced alkaline phosphatase (ALP) activity, Alizarin red staining, gene expression of Runx2, Osteopontin (OPN), Type I collagen (COL1a1) in culture. Additionally, BMP signaling responsive reporter activity and phosphor-smad1/5/8 expression were also significantly increased upon removal of RBPJK in MSCs. These data proved that inhibition of Notch signaling in MSCs promotes cell osteogenic differentiation by up-regulation of BMP signaling, and RBPJK deficient MSC maybe a better cell population for cell based bone tissue engineering. PMID- 26285014 TI - Impact of AMP-Activated Protein Kinase alpha1 Deficiency on Tissue Injury following Unilateral Ureteral Obstruction. AB - BACKGROUND: AMP-activated protein kinase (Ampk) is a sensor of the cellular energy status and a powerful regulator of metabolism. Activation of Ampk was previously shown to participate in monocyte-to-fibroblast transition and matrix protein production in renal tissue. Thus, the present study explored whether the catalytic Ampkalpha1 isoform participates in the regulation of the renal fibrotic response following unilateral ureteral obstruction (UUO). METHODS: UUO was induced in gene-targeted mice lacking functional Ampkalpha1 (Ampkalpha1-/-) and in corresponding wild-type mice (Ampkalpha1+/+). In the obstructed kidney and, for comparison, in the non-obstructed control kidney, quantitative RT-PCR, Western blotting and immunostaining were employed to determine transcript levels and protein abundance, respectively. RESULTS: In Ampkalpha1+/+ mice, UUO significantly up-regulated the protein abundance of the Ampkalpha1 isoform, but significantly down-regulated the Ampkalpha2 isoform in renal tissue. Phosphorylated Ampkalpha protein levels were significantly increased in obstructed kidney tissue of Ampkalpha1+/+ mice but not of Ampkalpha1-/- mice. Renal expression of alpha-smooth muscle actin was increased following UUO, an effect again less pronounced in Ampkalpha1-/- mice than in Ampkalpha1+/+ mice. Histological analysis did not reveal a profound effect of Ampkalpha1 deficiency on collagen 1 protein deposition. UUO significantly increased phosphorylated and total Tgf-beta-activated kinase 1 (Tak1) protein, as well as transcript levels of Tak1-downstream targets c-Fos, Il6, Pai1 and Snai1 in Ampkalpha1+/+ mice, effects again significantly ameliorated in Ampkalpha1-/- mice. Moreover, Ampkalpha1 deficiency inhibited the UUO-induced mRNA expression of Cd206, a marker of M2 macrophages and of Cxcl16, a pro-fibrotic chemokine associated with myeloid fibroblast formation. The effects of Ampkalpha1 deficiency during UUO were, however, paralleled by increased tubular injury and apoptosis. CONCLUSIONS: Renal obstruction induces an isoform shift from Ampkalpha2 towards Ampkalpha1, which contributes to the signaling involved in cell survival and fibrosis. PMID- 26285016 TI - A Survey of Increased Infectious Risk Donor Utilization in Canadian Transplant Programs. AB - BACKGROUND: Donors at increased risk of transmitting viral infections are a potential source of transplantable organs. Studies demonstrate that organs from increased risk donors (IRDs) are associated with excellent outcomes. However, considerable variation in practice likely exists. METHODS: We performed a cross country survey of Canadian Organ Transplant centers to determine organ utilization practices from IRDs. RESULTS: Of 40 surveys sent to transplant programs across Canada, 24 (60%) were returned. Of those, 60.9% (15/24) had a formal policy for their use, and 21.7% (5/24) had never accepted an IRD. Only 41.7% (10/24) had access to timely nucleic acid testing (NAT), and respondents were more likely to accept IRD if NAT was available. For example the likelihood of using organs from an intravenous drug user increased from 12.5% (4/24) with serology negative donors to 70.8% (17/24) if NAT was available and the donor had no increased activity within the window period (P < 0.001). Only 37.5% (9/24) discussed the use of IRDs with candidates at listing, with 54.2% (13/24) stating that having a standardized consent would increase utilization of IRDs. CONCLUSIONS: The results suggest that availability of NAT would increase IRD utilization. In addition written policies and procedures on IRD use and the consent process would be recommended in many Canadian centers. PMID- 26285015 TI - Evidence to Support a Contribution of Polyreactive Antibodies to HLA Serum Reactivity. AB - BACKGROUND: Assessing the serum reactivity to HLA is essential for the evaluation of transplant candidates and the follow-up of allograft recipients. In this study, we look for evidence at the clonal level that polyreactive antibodies cross-reactive to apoptotic cells and multiple autoantigens can also react to HLA and contribute to the overall serum reactivity. METHODS: We immortalized B cell clones from the blood of 2 kidney transplant recipients and characterized their reactivity to self-antigens, apoptotic cells as well as native, denatured, and cryptic HLA determinants using enzyme-linked immunosorbent assay (ELISA), immunofluorescence, flow cytometry and Luminex assays. We also assessed the reactivity of 300 pretransplant serum specimens to HLA and apoptotic cells. RESULTS: We report here 4 distinct B cell clones cross-reactive to self and HLA class I. All 4 clones reacted to numerous HLA class I alleles but did not appear to target canonical "shared" epitopes. In parallel experiments, we observed a strong correlation between IgG reactivity to HLA and apoptotic cells in pretransplant serum samples collected from 300 kidney transplant recipients. Further analysis revealed that samples with higher reactivity to apoptotic cells displayed significantly higher class I percent panel-reactive antibodies compared to samples with low reactivity to apoptotic cells. CONCLUSIONS: We provide here (1) proof of principle at the clonal level that human polyreactive antibodies can cross-react to HLA, multiple self-antigens and apoptotic cells and (2) supportive evidence that polyreactive antibodies contribute to overall HLA reactivity in the serum of patients awaiting kidney transplant. PMID- 26285017 TI - Immunological and Fibrotic Mechanisms in Cardiac Allograft Vasculopathy. AB - Cardiac allograft vasculopathy (CAV) has a high prevalence among patients that have undergone heart transplantation. Cardiac allograft vasculopathy is a multifactorial process in which the immune system is the driving force. In this review, the data on the immunological and fibrotic processes that are involved in the development of CAV are summarized. Areas where a lack of knowledge exists and possible additional research can be completed are pinpointed. During the pathogenesis of CAV, cells from the innate and the adaptive immune system cooperate to reject the foreign heart. This inflammatory response results in dysfunction of the endothelium and migration and proliferation of smooth muscle cells (SMCs). Apoptosis and factors secreted by both the endothelium as well as the SMCs lead to fibrosis. The migration of SMCs together with fibrosis provoke concentric intimal thickening of the coronary arteries, which is the main characteristic of CAV. PMID- 26285019 TI - Pediatric Chronic Dialysis in Brazil: Epidemiology and Regional Inequalities. AB - INTRODUCTION: There are few reports in the literature estimating the epidemiologic characteristics of pediatric chronic dialysis. These patients have impaired physical growth, high number of comorbidities and great need for continuous attention of specialized services with high demand for complex and costly procedures. OBJECTIVE: The aim of this study was to estimate the incidence and prevalence rates and describe the characteristics of children and adolescents undergoing chronic dialysis treatment in a Brazilian demographic health survey. MATERIALS AND METHODS: A cross-sectional study was performed in a representative sample of dialysis centers (nc = 239) that was established from the 2011 Brazilian Nephrology Society Census (Nc = 708). We collected data encompassing the five Brazilian macro-regions. We analyzed the data from all patients under 19 years of age. The sample population consisted of 643 children and adolescents who were on chronic dialysis program anytime in 2012. Data collection was carried out in the dialysis services by means of patients' records reviews and personal interviews with the centers' leaders. RESULTS: We estimated that there were a total of 1,283 pediatric patients on chronic dialysis treatment in Brazil, resulting in a prevalence of 20.0 cases per million age-related population (pmarp) (95% CI: 14.8-25.3) and an incidence of 6.6 cases pmarp in 2012 (95% CI: 4.8-8.4). The South region had the highest prevalence and incidence rates of patients under dialysis therapy, 27.7 (95% CI: 7.3-48.1) and 11.0 (95% CI: 2.8 19.3) cases pmarp, respectively; the lowest prevalence and incidence rates were found in the North-Midwest region, 13.8 (95% CI: 6.2-21.4), and in the Northeast region, 3.8 (95% CI: 1.4-6.3) cases pmarp, respectively. CONCLUSION: Brazil has an overall low prevalence of children on chronic dialysis treatment, figuring near the rates from others countries with same socioeconomic profile. There are substantial differences among regions related to pediatric chronic dialysis treatment. Joint strategies aiming to reduce inequities and improving access to treatment and adequacy of services across the Brazilian regions are necessary to provide an appropriate care setting for this population group. PMID- 26285018 TI - Donor Hepatic Steatosis Induce Exacerbated Ischemia-Reperfusion Injury Through Activation of Innate Immune Response Molecular Pathways. AB - BACKGROUND: Severe liver steatosis is a known risk factor for increased ischemia reperfusion injury (IRI) and poor outcomes after liver transplantation (LT). This study aimed to identify steatosis-related molecular mechanisms associated with IRI exacerbation after LT. METHODS: Paired graft biopsies (n = 60) were collected before implantation (L1) and 90 minutes after reperfusion (L2). The LT recipients (n = 30) were classified by graft macrosteatosis: without steatosis (WS) of 5% or less (n = 13) and with steatosis (S) of 25% or greater (n = 17). Plasma samples were collected at L1, L2, and 1 day after LT (postoperative [POD]1) for cytokines evaluation. Tissue RNA was isolated for gene expression microarrays. Probeset summaries were obtained using robust multiarray average algorithm. Pairwise comparisons were fit using 2-sample t test. P values 0.01 or less were significant (false discovery rate <5%). Molecular pathway analyses were conducted using Ingenuity Pathway Analysis tool. RESULTS: Significantly differentially expressed genes were identified for WS and S grafts after reperfusion. Comprehensive comparison analysis of molecular profiles revealed significant association of S grafts molecular profile with innate immune response activation, macrophage production of nitric oxide and reactive oxygen species, IL-6, IL-8, IL 10 signaling activation, recruitment of granulocytes, and accumulation of myeloid cells. Postreperfusion histological patterns of S grafts revealed neutrophilic infiltration surrounding fat accumulation. Circulating proinflammatory cytokines after reperfusion and 24 hours after LT concurred with intragraft-deregulated molecular pathways. All tested cytokines were significantly increased in plasma of S grafts recipients after reperfusion when compared with WS group at same time. CONCLUSIONS: Increases of graft steatosis exacerbate IRI by exacerbation of innate immune response after LT. Preemptive strategies should consider it for safety usage of steatotic livers. PMID- 26285020 TI - Effect of Caffeine on Golf Performance and Fatigue during a Competitive Tournament. AB - PURPOSE: This study aimed to determine the effect of a caffeine-containing supplement on golf-specific performance and fatigue during a 36-hole competitive golf tournament. METHODS: Twelve male golfers (34.8 +/- 13.9 yr, 175.9 +/- 9.3 cm, 81.23 +/- 13.14 kg) with a United States Golf Association handicap of 3-10 participated in a double-blind, placebo-controlled, crossover design in which they played an 18-hole round of golf on two consecutive days (36-hole tournament) and were randomly assigned to consume a caffeine-containing supplement (CAF) or placebo (PLA). CAF/PLA was consumed before and after nine holes during each 18 hole round. Total score, drive distance, fairways and greens in regulation, first putt distance, HR, breathing rate, peak trunk acceleration, and trunk posture while putting were recorded. Self-perceived ratings of energy, fatigue, alertness and concentration were also recorded. RESULTS: Total score (76.9 +/- 8.1 vs 79.4 +/- 9.1, P = 0.039), greens in regulation (8.6 +/- 3.3 vs 6.9 +/- 4.6, P = 0.035), and drive distance (239.9 +/- 33.8 vs 233.2 +/- 32.4, P = 0.047) were statistically better during the CAF condition compared with those during PLA. Statistically significant main effects for condition (P < 0.05) and time (P < 0.001) occurred for perceived feelings of energy and fatigue. Compared with PLA, CAF reported more energy (P = 0.025) and less fatigue (P = 0.05) over the competitive round of golf. There were no substantial differences in HR or breathing rates, peak trunk acceleration, or putting posture between conditions or over the round (P > 0.05). CONCLUSIONS: A moderate dose (1.9 +/- 0.3 mg . kg( 1)) of caffeine consumed before and during a round of golf improves golf-specific measures of performance and reduces fatigue in skilled golfers. PMID- 26285021 TI - Effects of Standing and Light-Intensity Activity on Ambulatory Blood Pressure. AB - PURPOSE: This study aimed to compare ambulatory blood pressure (ABP) response to accumulated standing (STAND), cycling (CYCLE), and walking (WALK) to a sitting only (SIT) day in adults. METHODS: Nine overweight or obese (body mass index, 28.7 +/- 2.7 kg . m(-2)) adults (30 +/- 15 yr) participated in this randomized crossover full-factorial study. Four conditions (WALK, STAND, CYCLE, and SIT) were randomly performed 1 wk apart. WALK, STAND, and CYCLE conditions consisted of progressively increasing activity time to accumulate 2.5 h during an 8-h simulated workday. WALK (1.0 mph) and STAND (0.0 mph) were completed on a treadmill placed underneath a standing-height desk. During CYCLE, participants pedaled on a Monark cycle ergometer at a cadence and energy expenditure equivalent to WALK. Participants remained seated during the SIT condition. Participants wore an ABP cuff from 0800 h until 2200 h on all conditions. Linear mixed models were used to test condition differences in systolic (SBP) and diastolic (DBP) blood pressure. Chi-square was used to detect frequency difference of BP load. RESULTS: There was a whole-day (during and after work hours) SBP and DBP treatment effect (P < 0.01). Systolic blood pressure during STAND (132 +/- 17 mm Hg), WALK (133 +/- 17 mm Hg), and CYCLE (130 +/- 16 mm Hg) were lower compared with that during SIT (137 +/- 17 mm Hg) (all P < 0.01). CYCLE was lower than STAND (P = 0.04) and WALK (P < 0.01). For DBP, only CYCLE (69 +/- 12 mm Hg) was lower than SIT (71 +/- 13 mm Hg; P < 0.01). Compared with SIT, WALK, STAND, and CYCLE reduced SBP load by 4%, 4%, and 13%, respectively (all P < 0.01). CONCLUSIONS: Compared with sitting, accumulating 2.5 h of light-intensity physical activity or standing during an 8-h workday may reduce ABP during and after work hours. PMID- 26285022 TI - Impact of Exercise Timing on Appetite Regulation in Individuals with Type 2 Diabetes. AB - PURPOSE: Exercise improves appetite regulation, but it is not known if premeal or postmeal exercise more effectively improves appetite regulation in individuals with type 2 diabetes. For the first time, this study compared how premeal and postmeal exercise alters appetite regulation in individuals with type 2 diabetes. METHODS: Twelve obese individuals with type 2 diabetes performed 3 different trials, all in a random order, in which they consumed a dinner meal with the following: no resistance exercise (RE), premeal RE, or postmeal RE beginning 45 min after dinner. A visual analog scale was used to assess perceived hunger and fullness, and frequent blood samples were drawn for determination of acylated ghrelin, pancreatic polypeptide (PP), and peptide tyrosine tyrosine (PYY) concentrations. RESULTS: Premeal RE increased premeal perceived fullness, reduced perceived hunger, and reduced acylated ghrelin concentrations compared with the no RE and postmeal RE trial (P < 0.05). In the postprandial period, both premeal and postmeal RE reduced perceived hunger compared with no RE, whereas only postmeal RE reduced postprandial perceived fullness (P < 0.05) compared with no RE. Premeal or postmeal RE did not alter PYY concentrations. In both the premeal and postprandial period, RE reduced PP concentrations compared with no RE (P < 0.05), but upon cessation of RE, PP concentrations rebounded to concentrations that were similar to no RE. CONCLUSIONS: Both premeal and postmeal RE reduced perceived hunger and increased perceived fullness, effects that may help control food intake and aid in weight management efforts in individuals with type 2 diabetes. PMID- 26285023 TI - Tyrosine Ingestion and Its Effects on Cognitive and Physical Performance in the Heat. AB - PURPOSE: Ingestion of tyrosine (TYR), a catecholamine precursor, has previously improved aspects of cognitive function and mood during acute stress, although there is limited research exploring the optimal dose relative to blood values. The serum responses of two doses of TYR were investigated (study 1), with the identified "optimal" dose assessed relative to cognitive and physical performance during a military-based protocol in the heat (study 2). METHODS: For study 1, 21 participants were assigned to one of the following three groups: HIGH (two doses of 150 mg . kg(-1) body mass TYR), LOW (two doses of 75 mg . kg(-1) body mass TYR), and CON (sugar-free drink). Participants ingested TYR in two separate doses (0900 and 1300 h) and remained in the laboratory from 0800 to 1700 h, having blood drawn every hour. For study 2, eight participants completed a military based load carriage protocol composed of a 60-min walk (6.5 km . h(-1)) followed by a 2.4-km time trial carrying a 25-kg backpack (40 degrees C; relative humidity, 30%) on two occasions (TYR/placebo) in a double-blind counterbalanced crossover design. Cognitive function was assessed before, during, and after exercise. RESULTS: Study 1 demonstrated that ingestion of a single dose of 150 mg . kg(-1) body mass TYR was equally efficient at elevating serum TYR concentration relative to a double dose. In study 2, exercise heat stress impaired some aspects of cognitive function; however, TYR did not alleviate these decrements (P > 0.05). Furthermore, no difference was observed in any physiological variable between conditions (P > 0.05) or time trial completion time (P = 0.74) between TYR (19.78 +/- 3.44 min) and placebo (20.29 +/- 3.55 min). CONCLUSIONS: Despite marked elevations in serum TYR concentration, ingestion of TYR did not influence cognitive function or physical performance during exercise heat stress. PMID- 26285024 TI - Endurance Training Attenuates Catabolic Signals Induced by TNF-alpha in Muscle of Mice. AB - PURPOSE: To determine whether endurance training attenuates the negative effects induced by an acute injection of tumor necrosis factor-alpha (TNF-alpha) in skeletal muscle of mice. METHODS: Trained (6 wk of endurance training at 60% of maximal velocity) and untrained mice were injected with TNF-alpha or vehicle and killed 6 h after. Tibialis anterior muscles were analyzed using Western blot and qRT-PCR for markers of inflammation and protein synthesis/degradation. RESULTS: Independently of training, TNF-alpha increased the mRNA of cytokines and downregulated signals linked to protein synthesis. The phosphorylation of IKKalpha/beta and IkappaBalpha induced by TNF-alpha was blunted in trained mice, suggesting altered NF-kappaB activation. This was associated with lower induction of several markers of protein degradation (FoxO1, MURF1, MAFbx, myostatin, Gabarapl1, and LC3BII/LC3BI ratio). CONCLUSIONS: Endurance training protects skeletal muscle against the activation of protein degradation signaling pathways induced by TNF-alpha. PMID- 26285025 TI - The Healthy Mind, Healthy Mobility Trial: A Novel Exercise Program for Older Adults. AB - BACKGROUND: More evidence is needed to conclude that a specific program of exercise and/or cognitive training warrants prescription for the prevention of cognitive decline. We examined the effect of a group-based standard exercise program for older adults, with and without dual-task training, on cognitive function in older adults without dementia. METHODS: We conducted a proof-of concept, single-blinded, 26-wk randomized controlled trial whereby participants recruited from preexisting exercise classes at the Canadian Centre for Activity and Aging in London, Ontario, were randomized to the intervention group (exercise + dual-task [EDT]) or the control group (exercise only [EO]). Each week (2 or 3 d . wk(-1)), both groups accumulated a minimum of 50 min of aerobic exercise (target 75 min) from standard group classes and completed 45 min of beginner level square-stepping exercise. The EDT group was also required to answer cognitively challenging questions while doing beginner-level square-stepping exercise (i.e., dual-task training). The effect of interventions on standardized global cognitive function (GCF) scores at 26 wk was compared between the groups using the linear mixed effects model approach. RESULTS: Participants (n = 44; 68% female; mean [SD] age: 73.5 [7.2] yr) had on average, objective evidence of cognitive impairment (Montreal Cognitive Assessment scores, mean [SD]: 24.9 [1.9]) but not dementia (Mini-Mental State Examination scores, mean [SD]: 28.8 [1.2]). After 26 wk, the EDT group showed greater improvement in GCF scores compared with the EO group (difference between groups in mean change [95% CI]: 0.20 SD [0.01-0.39], P = 0.04). CONCLUSIONS: A 26-wk group-based exercise program combined with dual-task training improved GCF in community-dwelling older adults without dementia. PMID- 26285026 TI - Molecular Typing of Mycobacterium Tuberculosis Complex by 24-Locus Based MIRU VNTR Typing in Conjunction with Spoligotyping to Assess Genetic Diversity of Strains Circulating in Morocco. AB - BACKGROUND: Standard 24-locus Mycobacterial Interspersed Repetitive Unit Variable Number Tandem Repeat (MIRU-VNTR) typing allows to get an improved resolution power for tracing TB transmission and predicting different strain (sub) lineages in a community. METHODOLOGY: During 2010-2012, a total of 168 Mycobacterium tuberculosis Complex (MTBC) isolates were collected by cluster sampling from 10 different Moroccan cities, and centralized by the National Reference Laboratory of Tuberculosis over the study period. All isolates were genotyped using spoligotyping, and a subset of 75 was genotyped using 24-locus based MIRU-VNTR typing, followed by first line drug susceptibility testing. Corresponding strain lineages were predicted using MIRU-VNTRplus database. PRINCIPAL FINDINGS: Spoligotyping resulted in 137 isolates in 18 clusters (2-50 isolates per cluster: clustering rate of 81.54%) corresponding to a SIT number in the SITVIT database, while 31(18.45%) patterns were unique of which 10 were labelled as "unknown" according to the same database. The most prevalent spoligotype family was LAM; (n = 81 or 48.24% of isolates, dominated by SIT42, n = 49), followed by Haarlem (23.80%), T superfamily (15.47%), >Beijing (2.97%), > U clade (2.38%) and S clade (1.19%). Subsequent 24-Locus MIRU-VNTR typing identified 64 unique types and 11 isolates in 5 clusters (2 to 3isolates per cluster), substantially reducing clusters defined by spoligotyping only. The single cluster of three isolates corresponded to two previously treated MDR-TB cases and one new MDR-TB case known to be contact a same index case and belonging to a same family, albeit residing in 3 different administrative regions. MIRU-VNTR loci 4052, 802, 2996, 2163b, 3690, 1955, 424, 2531, 2401 and 960 were highly discriminative in our setting (HGDI >0.6). CONCLUSIONS: 24-locus MIRU-VNTR typing can substantially improve the resolution of large clusters initially defined by spoligotyping alone and predominating in Morocco, and could therefore be used to better study tuberculosis transmission in a population-based, multi-year sample context. PMID- 26285028 TI - Temperature-Correlated Changes in Phytoplankton Community Structure Are Restricted to Polar Waters. AB - Globally distributed observations of size-fractionated chlorophyll a and temperature were used to incorporate temperature dependence into an existing semi empirical model of phytoplankton community size structure. The additional temperature-dependent term significantly increased the model's ability to both reproduce and predict observations of chlorophyll a size-fractionation at temperatures below 2 degrees C. The most notable improvements were in the smallest (picoplankton) size-class, for which overall model fit was more than doubled, and predictive skill was increased by approximately 40%. The model was subsequently applied to generate global maps for three phytoplankton size classes, on the basis of satellite-derived estimates of surface chlorophyll a and sea surface temperature. Polar waters were associated with marked decline in the chlorophyll a biomass of the smallest cells, relative to lower latitude waters of equivalent total chlorophyll a. In the same regions a complementary increase was seen in the chlorophyll a biomass of larger size classes. These findings suggest that a warming and stratifying ocean will see a poleward expansion of the habitat range of the smallest phytoplankton, with the possible displacement of some larger groups that currently dominate. There was no evidence of a strong temperature dependence in tropical or sub-tropical regions, suggesting that future direct temperature effects on community structure at lower latitudes may be small. PMID- 26285027 TI - Stroking or Buzzing? A Comparison of Somatosensory Touch Stimuli Using 7 Tesla fMRI. AB - Studying body representations in the brain helps us to understand how we humans relate to our own bodies. The in vivo mapping of the somatosensory cortex, where these representations are found, is greatly facilitated by the high spatial resolution and high sensitivity to brain activation available at ultra-high field. In this study, the use of different stimulus types for somatotopic mapping of the digits at ultra-high field, specifically manual stroking and mechanical stimulation, was compared in terms of sensitivity and specificity of the brain responses. Larger positive responses in digit regions of interest were found for manual stroking than for mechanical stimulation, both in terms of average and maximum t-value and in terms of number of voxels with significant responses to the tactile stimulation. Responses to manual stroking were higher throughout the entire post-central sulcus, but the difference was especially large on its posterior wall, i.e. in Brodmann area 2. During mechanical stimulation, cross digit responses were more negative than during manual stroking, possibly caused by a faster habituation to the stimulus. These differences indicate that manual stroking is a highly suitable stimulus for fast somatotopic mapping procedures, especially if Brodmann area 2 is of interest. PMID- 26285029 TI - Identification of Postpartum Depression in an Online Community. AB - OBJECTIVE: To identify the rate of postpartum depression symptoms in an online community. A secondary purpose was to identify women's experiences when accessing health care services for postpartum depression (PPD). DESIGN: A quantitative, cross-sectional, survey design. SETTING: The setting consisted of nine birth clubs from one online community specifically targeted toward new mothers. PARTICIPANTS: A convenience sample of 469 mostly married (n = 373), White (n = 401) mothers with a mean age of 29.3 (SD = 5.3) years took part in this study. The majority (n = 433) reported living in the United States with access to health insurance coverage. METHODS: The Edinburgh Postnatal Depression Scale (EPDS) was used to assess depression symptoms. Mothers indicating a previous diagnosis of PPD also completed the Access to Postpartum Depression Care (APDC) questionnaire. RESULTS: Total EPDS scores ranged from 0 to 27 with a median of 7.0. Sixteen percent of participants (n = 75) scored >= 13, indicating a high risk for developing PPD. Of these 75 mothers, 18 (24%) indicated having thoughts of harming themselves sometimes and five (7%) indicated having these thoughts quite often. Additionally, 76 mothers indicating a previous history of PPD also completed the APDC questionnaire. Findings suggested mothers often received care that did not meet their expectations. Barriers to PPD care included insurance limitations and insensitive comments from their health care providers. CONCLUSIONS: The rate of depression symptoms noted in this Internet-based population is in agreement with published rates. Therefore, findings of this study support further exploration and evaluation of using online platforms for PPD screening. PMID- 26285030 TI - Interaction of Vibrio spp. with the Inner Surface of the Digestive Tract of Penaeus monodon. AB - Several species of Vibrio are the causative agent of gastroenteritis in humans. In aquaculture, Vibrio harveyi (Vh) and V. parahaemolyticus (Vp) have long been considered as shrimp pathogens in freshwater, brackish and marine environments. Here we show by using scanning electron microscopy (SEM) that Penaeus monodon orally inoculated with each of these two pathogens via an Artemia diet had numerous bacteria attached randomly across the stomach surface, in single and in large biofilm-like clusters 6 h post-infection. A subsequent marked proliferation in the number of V. harveyi within the biofilm-like formations resulted in the development of infections in the stomach, the upper and middle midgut, but neither in the posterior midgut nor the hindgut. SEM also revealed the induced production of peritrichous pili-like structures by the Vp attaching to the stomach lining, whilst only a single polar fibre was seen forming an apparent physical bridge between Vh and the host's epithelium. In contrast to these observations, no such adherences or linkages were seen when trials were conducted with non-pathogenic Vibrio spp. or with Micrococcus luteus, with no obvious resultant changes to the host's gut surface. In naive shrimp, the hindgut was found to be a favorable site for bacteria notably curved, short-rod shaped bacteria which probably belong to Vibrio spp. Data from the current study suggests that pathogens of P. monodon must be able to colonize the digestive tract, particularly the stomach, where chitin is present, and then they use an array of virulent factors and enzymes to infect their host resulting in disease. Oral infection is a better way of mimicking natural routes of infection; investigating the host-bacteria interactions occurring in the digestive tract may lead to new strategies for the prevention or control of bacterial infections in penaeids. PMID- 26285031 TI - Prevalence of Neurocysticercosis in People with Epilepsy in the Eastern Province of Zambia. AB - Zambia is endemic for Taenia solium taeniosis and cysticercosis. In this single centered, cross-sectional, community-based study, the role of neurocysticercosis (NCC) as a cause of epilepsy was examined. People with epilepsy (PWE, n = 56) were identified in an endemic area using a screening questionnaire followed by in depth interviews and neurological examination. Computed tomography (CT) was performed on 49 people with active epilepsy (PWAE) and their sera (specific antibody and antigen detection, n = 56) and stools (copro-antigen detection, n = 54) were analyzed. The CT scan findings were compared to a group of 40 CT scan controls. Of the PWE, 39.3% and 23.2% were positive for cysticercal antibodies and antigens, respectively, and 14.8% for coproantigens (taeniosis). Lesions highly suggestive of NCC were detected in 24.5% and definite NCC lesions in 4.1% of CT scans of PWAE. This compares to 2.5% and 0%, respectively, in the control CT scans. Using the Del Brutto diagnostic criteria, 51.8% of the PWAE were diagnosed with probable or definitive NCC and this rose to 57.1% when the adapted criteria, as proposed by Gabriel et al. (adding the sero-antigen ELISA test as a major criterion), were used. There was no statistically significant relationship between NCC, current age, age at first seizure and gender. This study suggests that NCC is the single most important cause of epilepsy in the study area. Additional large-scale studies, combining a community based prevalence study for epilepsy with neuroimaging and serological analysis in different areas are needed to estimate the true impact of neurocysticercosis in endemic regions and efforts should be instituted to the control of T. solium. PMID- 26285032 TI - Vapor-Driven Propulsion of Catalytic Micromotors. AB - Chemically-powered micromotors offer exciting opportunities in diverse fields, including therapeutic delivery, environmental remediation, and nanoscale manufacturing. However, these nanovehicles require direct addition of high concentration of chemical fuel to the motor solution for their propulsion. We report the efficient vapor-powered propulsion of catalytic micromotors without direct addition of fuel to the micromotor solution. Diffusion of hydrazine vapor from the surrounding atmosphere into the sample solution is instead used to trigger rapid movement of iridium-gold Janus microsphere motors. Such operation creates a new type of remotely-triggered and powered catalytic micro/nanomotors that are responsive to their surrounding environment. This new propulsion mechanism is accompanied by unique phenomena, such as the distinct off-on response to the presence of fuel in the surrounding atmosphere, and spatio temporal dependence of the motor speed borne out of the concentration gradient evolution within the motor solution. The relationship between the motor speed and the variables affecting the fuel concentration distribution is examined using a theoretical model for hydrazine transport, which is in turn used to explain the observed phenomena. The vapor-powered catalytic micro/nanomotors offer new opportunities in gas sensing, threat detection, and environmental monitoring, and open the door for a new class of environmentally-triggered micromotors. PMID- 26285033 TI - Habitat changes and changing predatory habits in North American fossil canids. AB - The spread of open grassy habitats and the evolution of long-legged herbivorous mammals with high-crowned cheek teeth have been viewed as an example of coevolution. Previous studies indicate that specialized predatory techniques in carnivores do not correlate with the spread of open habitats in North America. Here we analyse new data on elbow-joint shape for North American canids over the past ~37 million years and show that incipiently specialized species first appeared along with the initial spread of open habitats in the late Oligocene. Elbow-joint morphologies indicative of the behavior of modern pounce-pursuit predators emerged by the late Miocene coincident with a shift in plant communities from C3 to C4 grasses. Finally, pursuit canids first emerged during the Pleistocene. Our results indicate that climate change and its impact on vegetation and habitat structure can be critical for the emergence of ecological innovations and can alter the direction of lineage evolution. PMID- 26285034 TI - Glycemic Control and Mortality in Diabetic Patients Undergoing Dialysis Focusing on the Effects of Age and Dialysis Type: A Prospective Cohort Study in Korea. AB - BACKGROUND: Active glycemic control has been proven to delay the onset and slow the progression of diabetic retinopathy, nephropathy, and neuropathy in diabetic patients, but the optimal level is obscure in end-stage renal disease. In this study, we evaluated the effect of hemoglobin A1c (HbA1c) on mortality of diabetic patients on dialysis, focusing on age and dialysis type. METHODS: Of 3,302 patients enrolled in the prospective cohort for end-stage renal disease in Korea between August 2008 and October 2013, 1,239 diabetic patients who had been diagnosed with diabetes or having HbA1c>=6.5% at the time of enrollment were analyzed. Age was categorized as <55, 55-64 and >=65 years old. Age, sex, modified Charlson comorbidity index, hemoglobin, primary renal disease, body mass index, and dialysis duration were adjusted. RESULTS: A total of 873 patients received hemodialysis (HD) and 366 underwent peritoneal dialysis (PD). During the mean follow-up of 19.1 months, 141 patients died. Patients with poor glucose control (HbA1c>=8%) showed worse survival than patients with HbA1c<8% (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.48-3.29; P<0.001). Subgroup analysis divided by age revealed that HbA1c>=8% was a predictor of mortality in age <55 (HR, 4.3; 95% CI, 1.78-10.41; P = 0.001) and age 55-64 groups (HR, 3.3; 95% CI, 1.56-7.05; P = 0.002), but not in age >=65 group. Combining dialysis type and age, poor glucose control negatively affected survival only in age < 55 group among HD patients, but it was significant in age < 55 and age 55-64 groups in PD patients. Deaths from infection were more prevalent in the PD group, and poor glucose control tended to correlate with more deaths from infection in PD patients (P = 0.050). CONCLUSIONS: In this study, the effect of glycemic control differed according to age and dialysis type in diabetic patients. Thus, the target of glycemic control should be customized; further observational studies may strengthen the clinical relevance. PMID- 26285038 TI - Financial decision-making abilities and financial exploitation in older African Americans: Preliminary validity evidence for the Lichtenberg Financial Decision Rating Scale (LFDRS). AB - This study examines preliminary evidence for the Lichtenberg Financial Decision Rating Scale (LFDRS), a new person-centered approach to assessing capacity to make financial decisions, and its relationship to self-reported cases of financial exploitation in 69 older African Americans. More than one third of individuals reporting financial exploitation also had questionable decisional abilities. Overall, decisional ability score and current decision total were significantly associated with cognitive screening test and financial ability scores, demonstrating good criterion validity. Study findings suggest that impaired decisional abilities may render older adults more vulnerable to financial exploitation, and that the LFDRS is a valid tool. PMID- 26285040 TI - Associations Between Parental Perceptions of the Neighborhood Environment and Childhood Physical Activity: Results from ISCOLE-Kenya. AB - BACKGROUND: A physical activity transition to declining activity levels, even among children, now poses a serious public health concern because of its contribution to a rising prevalence of noncommunicable diseases. Childhood physical activity levels are associated with parental perceptions of the neighborhood; however, these relationships have not been explored in sub-Saharan Africa (SSA). The objective was to investigate relationships between parental perceptions of the neighborhood and physical activity indicators among Kenyan children. METHODS: Data were collected from children 9 to 11 years old in Nairobi as part of the International Study of Childhood Obesity, Lifestyle and Environment. Child physical activity was assessed by accelerometry, and information on obtaining sufficient physical activity, active transport, and parental perceptions of the neighborhood collected using questionnaires. RESULTS: Of 563 participating children, 45.7%, 12.6%, and 11.4% used active school transportation, met physical activity guidelines, and were sufficiently active, respectively. Parental perception of positive neighborhood social cohesion, positive environs and connectivity, and negative child safety concerns, were associated with child physical activity outcomes. CONCLUSIONS: Aspects of parental perceptions of the neighborhood were associated with child physical activity outcomes and should be further explored to appropriately inform policy and practice in curbing declining physical activity levels among children in SSA. PMID- 26285041 TI - Parsimonious Determination of the Optimal Infectious Dose of a Pathogen for Nonhuman Primate Models. AB - The nonhuman primate (NHP) model is often the best experimental model for testing interventions designed to block infection by human pathogens, such as HIV, tuberculosis, and malaria. A physiological model may require the use of a limiting dose of the infectious agent, where only a fraction of animals become infected upon any given challenge. Determining the challenge dose of the pathogen in such experiments is critical to the success of the experiment: using too-high or too-low a challenge dose may lead to false negative results and an excessive use of animals. Here I define an optimized protocol for defining the dose of pathogen that infects 50% of the time (AID50); other challenge doses, e.g. AID80, can be easily calculated from the same data. This protocol minimizes the number of animals, as well as resources and procedures, while providing an estimate of the AID50 within 1.5-fold of the true value. PMID- 26285039 TI - Adaptation of the Mitochondrial Genome in Cephalopods: Enhancing Proton Translocation Channels and the Subunit Interactions. AB - Mitochondrial protein-coding genes (mt genes) encode subunits forming complexes of crucial cellular pathways, including those involved in the vital process of oxidative phosphorylation (OXPHOS). Despite the vital role of the mitochondrial genome (mt genome) in the survival of organisms, little is known with respect to its adaptive implications within marine invertebrates. The molluscan Class Cephalopoda is represented by a marine group of species known to occupy contrasting environments ranging from the intertidal to the deep sea, having distinct metabolic requirements, varied body shapes and highly advanced visual and nervous systems that make them highly competitive and successful worldwide predators. Thus, cephalopods are valuable models for testing natural selection acting on their mitochondrial subunits (mt subunits). Here, we used concatenated mt genes from 17 fully sequenced mt genomes of diverse cephalopod species to generate a robust mitochondrial phylogeny for the Class Cephalopoda. We followed an integrative approach considering several branches of interest-covering cephalopods with distinct morphologies, metabolic rates and habitats-to identify sites under positive selection and localize them in the respective protein alignment and/or tridimensional structure of the mt subunits. Our results revealed significant adaptive variation in several mt subunits involved in the energy production pathway of cephalopods: ND5 and ND6 from Complex I, CYTB from Complex III, COX2 and COX3 from Complex IV, and in ATP8 from Complex V. Furthermore, we identified relevant sites involved in protein-interactions, lining proton translocation channels, as well as disease/deficiencies related sites in the aforementioned complexes. A particular case, revealed by this study, is the involvement of some positively selected sites, found in Octopoda lineage in lining proton translocation channels (site 74 from ND5) and in interactions between subunits (site 507 from ND5) of Complex I. PMID- 26285042 TI - Utilization of (18-crown-6)-2,3,11,12-tetracarboxylic acid as a chiral NMR solvating agent for diamines and beta-amino acids. AB - The compound (18-crown-6)-2,3,11,12-tetracarboxylic acid was evaluated as a chiral nuclear magnetic resonance (NMR) solvating agent for a series of diamines and bicyclic beta-amino acids. The amine must be protonated for strong association with the crown ether. An advantage of (18-crown-6)-2,3,11,12 tetracarboxylic acid over many other crown ethers is that it undergoes a neutralization reaction with neutral amines to form the protonated species needed for binding. Twelve primary diamines in neutral and protonated forms were evaluated. Diamines with aryl and aliphatic groups were examined. Some are atropisomers with equivalent amine groups. Others have two nonequivalent amine groups. Association equilibria for these systems are complex, given the potential formation of 2:1, 1:1, and 1:2 crown-amine complexes and given the various charged species in solution for mixtures of the crown ether with the neutral amine. The crown ether produced enantiomeric differentiation in the (1) H NMR spectrum of one or more resonances for every diamine substrate. Also, a series of five bicyclic beta-amino acids were examined and (18-crown-6)-2,3,11,12 tetracarboxylic acid caused enantiomeric differentiation in the (1) H NMR spectrum of three or more resonances of each compound. PMID- 26285044 TI - Group B Streptococci serotype distribution in pregnant women in Ghana: assessment of potential coverage through future vaccines. AB - OBJECTIVE: Group B streptococcal (GBS) colonization of pregnant women can lead to subsequent infection of the new-born and potentially fatal invasive disease. Data on GBS colonization prevalence and serotype distribution from Africa are scarce, although GBS-related infections are estimated to contribute substantially to infant mortality. In recent years, GBS vaccine candidates provided promising results in phase I and II clinical trials. We aimed to assess the prevalence and serotype distribution of GBS in Ghana since this knowledge is a prerequisite for future evaluation of vaccine trials. METHODS: This double-centre study was conducted in one rural and one urban hospital in central Ghana, West Africa. Women in late pregnancy (>=35 weeks of gestation) attending the antenatal care clinic (ANC) provided recto-vaginal swabs for GBS testing. GBS isolates were analysed for serotype and antibiotic susceptibility. GBS-positive women were treated with intrapartum antibiotic prophylaxis (IAP) according to current guidelines of the Center for Disease Control and Prevention (CDC). RESULTS: In total, 519 women were recruited at both study sites, recto-vaginal swabs were taken from 509. The overall prevalence of GBS was 19.1% (18.1% in rural Pramso and 23.1% in urban Kumasi, restrospectively). Capsular polysaccharide serotype (CPS) Ia accounted for the most frequent serotype beyond all isolates (28.1%), followed by serotype V (27.1%) and III (21.9%). No resistance to Penicillin was found, resistances to second line antibiotics clindamycin and erythromycin were 3.1% and 1%, respectively. DISCUSSION: Group B Streptococcus serotype distribution in Ghana is similar to that worldwide, but variations in prevalence of certain serotypes between the urban and rural study site were high. Antibiotic resistance of GBS strains was surprisingly low in this study. PMID- 26285043 TI - TRPV1 Channels and Gastric Vagal Afferent Signalling in Lean and High Fat Diet Induced Obese Mice. AB - AIM: Within the gastrointestinal tract vagal afferents play a role in control of food intake and satiety signalling. Activation of mechanosensitive gastric vagal afferents induces satiety. However, gastric vagal afferent responses to mechanical stretch are reduced in high fat diet mice. Transient receptor potential vanilloid 1 channels (TRPV1) are expressed in vagal afferents and knockout of TRPV1 reduces gastro-oesophageal vagal afferent responses to stretch. We aimed to determine the role of TRPV1 on gastric vagal afferent mechanosensitivity and food intake in lean and HFD-induced obese mice. METHODS: TRPV1+/+ and -/- mice were fed either a standard laboratory diet or high fat diet for 20wks. Gastric emptying of a solid meal and gastric vagal afferent mechanosensitivity was determined. RESULTS: Gastric emptying was delayed in high fat diet mice but there was no difference between TRPV1+/+ and -/- mice on either diet. TRPV1 mRNA expression in whole nodose ganglia of TRPV1+/+ mice was similar in both dietary groups. The TRPV1 agonist N-oleoyldopamine potentiated the response of tension receptors in standard laboratory diet but not high fat diet mice. Food intake was greater in the standard laboratory diet TRPV1-/- compared to TRPV1+/+ mice. This was associated with reduced response of tension receptors to stretch in standard laboratory diet TRPV1-/- mice. Tension receptor responses to stretch were decreased in high fat diet compared to standard laboratory diet TRPV1+/+ mice; an effect not observed in TRPV1-/- mice. Disruption of TRPV1 had no effect on the response of mucosal receptors to mucosal stroking in mice on either diet. CONCLUSION: TRPV1 channels selectively modulate gastric vagal afferent tension receptor mechanosensitivity and may mediate the reduction in gastric vagal afferent mechanosensitivity in high fat diet-induced obesity. PMID- 26285045 TI - Fibrosis progression in patients treated for hepatitis C recurrence. PMID- 26285046 TI - Spaceflight-induced bone loss alters failure mode and reduces bending strength in murine spinal segments. AB - Intervertebral disc herniation rates are quadrupled in astronauts following spaceflight. While bending motions are main contributors to herniation, the effects of microgravity on the bending properties of spinal discs are unknown. Consequently, the goal of this study was to quantify the bending properties of tail discs from mice with or without microgravity exposure. Caudal motion segments from six mice returned from a 30-day Bion M1 mission and eight vivarium controls were loaded to failure in four-point bending. After testing, specimens were processed using histology to determine the location of failure, and adjacent motion segments were scanned with micro-computed tomography (MUCT) to quantify bone properties. We observed that spaceflight significantly shortened the nonlinear toe region of the force-displacement curve by 32% and reduced the bending strength by 17%. Flight mouse spinal segments tended to fail within the growth plate and epiphyseal bone, while controls tended to fail at the disc vertebra junction. Spaceflight significantly reduced vertebral bone volume fraction, bone mineral density, and trabecular thickness, which may explain the tendency of flight specimens to fail within the epiphyseal bone. Together, these results indicate that vertebral bone loss during spaceflight may degrade spine bending properties and contribute to increased disc herniation risk in astronauts. PMID- 26285047 TI - Stunting Is Associated with Food Diversity while Wasting with Food Insecurity among Underfive Children in East and West Gojjam Zones of Amhara Region, Ethiopia. AB - BACKGROUND: Food insecurity has detrimental effects in protecting child undernutrition.This study sought to determine the level of child undernutrition and its association with food insecurity. METHODS: A community based comparative cross-sectional study design involving multistage sampling technique was implemented from 24th of May to 20th of July 2013. Using two population proportion formula, a total of 4110 randomly selected households were included in the study. Availability of the productive safety net programme was used for grouping the study areas. A multiple linear regression model was used to assess the association between food insecurity and child malnutrition. Clustering effects of localities were controlled during analysis. RESULTS: Stunting (37.5%), underweight (22.0%) and wasting (17.1%) were observed in East Gojjam zone, while 38.3% stunting, 22.5% underweight, and 18.6% wasting for the West Gojjam zone. Food insecurity was significantly associated with wasting (beta = - 0.108, P < 0.05).Food diversity and number of meals the child ate per day significantly associated with stunting (beta = 0.039, P < 0.01) and underweight (beta = 0.035, P < 0.05) respectively. Residential area was the significant predictor of all indices. CONCLUSION: The magnitude of child undernutrition was found to be very high in the study areas. Food insecurity was the significant determinant of wasting. Food diversity and number of meals the child ate per day were the significant determinants of stunting and underweight respectively. Child nutrition intervention strategies should take into account food security, dietary diversity, and carefully specified with regard to residential locations. Addressing food insecurity is of paramount importance. PMID- 26285048 TI - Effects of the ionization in the tautomerism of uracil: A reaction electronic flux perspective. AB - The one-step tautomerization processes of uracil and its radical cation and radical anion have been investigated in the light of the reaction force and reaction electronic flux (REF) formalisms. The relative energies of the different tautomers as well as the corresponding tautomerization barriers have been obtained through the use of the G4 high-level ab initio method and by means of B3LYP/6-311+G(3df,2p)//B3LYP/6-311+G(d, p) calculations. Systematically, the enol radical cations are more stable in relative terms than the neutral, due to the higher ionization energy of the diketo forms with respect to the enolic ones. Conversely, the enol radical anions, with the only exception of the 2-keto-N1 anion, are found to be less stable than the neutral. The effects of the ionization are also sizable on the tautomerization barriers although this effect also depends on the particular tautomerization process. The reaction force analysis shows that all reactions are mainly activated through structural rearrangements that initiate the electronic activity. This electronic activity is monitored along the reaction coordinate through the REF that obeys a delicate balance between the acid and basic character of the atoms involved in the hydrogen transfer. PMID- 26285049 TI - An experimental and theoretical approach to investigate the effect of chain length on aminothiol adsorption and assembly on gold. AB - Despite the numerous studies on the self-assembled monolayers (SAMs) of alkylthiols on gold, the mechanisms involved, especially the nature and influence of the thiol-gold interface are still under debate. In this work the adsorption of aminothiols on Au(111) surfaces has been studied by using surface IR and X-ray photoelectron spectroscopy (XPS) as well as by density functional theory (DFT) modeling. Two aminothiols were used, cysteamine (CEA) and mercaptoundecylamine (MUAM), which contain two and eleven carbon atoms, respectively. By combining experimental and theoretical methods, it was possible to draw a molecular picture of the thiol-gold interface. The long-chain aminothiol produced better ordered SAMs, but, interestingly, the XPS data showed different sulfur binding environments depending on the alkyl chain length; an additional peak at low binding energy was observed upon CEA adsorption, which indicates the presence of sulfur in a different environment. DFT modeling showed that the positions of the sulfur atoms in the SAMs on gold with similar unit cells [(2?3*2?3)R30 degrees ] depended on the length of the alkyl chain. Short-chain alkylthiol SAMs were adsorbed more strongly than long-chain thiol SAMs and were shown to induce surface reconstruction by extracting atoms from the surface, possibly forming adatom/vacancy combinations that lead to the additional XPS peak. In the case of short alkylthiols, the thiol-gold interface governs the layer, CEA adsorbs strongly, and the mechanism is closer to single-molecule adsorption than self assembly, whereas for long chains, interactions between alkyl chains drive the system to self-assembly, leading to a higher level of SAM organization and restricting the influence of the sulfur-gold interface. PMID- 26285050 TI - Maternal fatty acid levels during pregnancy, childhood lung function and atopic diseases. The Generation R Study. AB - BACKGROUND: Maternal fatty acid status during pregnancy might influence foetal immunological development and subsequently the risk of childhood atopic diseases. OBJECTIVE: To examine the associations of maternal fatty acid levels during pregnancy with airway resistance and inflammation, asthma and eczema, in school age children. METHODS: This study among 4976 subjects was embedded in a population-based prospective cohort study. We measured maternal plasma glycerophospholipid fatty acid levels by gas chromatography during the second trimester of pregnancy (mean gestational age: 20.7 (+/- 1.1) weeks). At the age of 6 years, airway resistance and inflammation were measured by interrupter technique (Rint) and fractional exhaled nitric oxide (FeNO), and current physician-diagnosed asthma and eczema were assessed by ISAAC-based questionnaires. Multiple linear and logistic regression models were adjusted for socio-demographic, lifestyle and anthropometric factors. RESULTS: We did not observe consistent associations of maternal total polyunsaturated fatty acid (PUFA), total n-6 PUFA, total n-3 PUFA levels and n-6/n-3 PUFA ratio during pregnancy with child's Rint and FeNO. Higher maternal total PUFA and total n-6 PUFA levels were associated with a decreased risk of childhood asthma (odds ratios (95% confidence interval): 0.76 (0.60, 0.97) and 0.71 (0.52, 0.96) per standard deviation score (SDS) increase of total PUFA and total n-6 PUFA levels, respectively) and with an increased risk of childhood eczema (1.16 (1.05, 1.28) and 1.21 (1.07, 1.37)). The observed associations were partly explained by Linoleic acid (LA, C18:2n-6) levels. Maternal total n-3 PUFA levels and n-6/n-3 PUFA ratio were not associated with current asthma and eczema. The observed associations were not explained by child's PUFA intake. CONCLUSIONS AND CLINICAL RELEVANCE: Higher maternal total PUFA and total n-6 PUFA levels during pregnancy seem to influence the risk of atopic diseases in childhood. The underlying mechanisms need to be further explored. PMID- 26285051 TI - Familial cortical dysplasia caused by mutation in the mammalian target of rapamycin regulator NPRL3. AB - We describe first cousin sibling pairs with focal epilepsy, one of each pair having focal cortical dysplasia (FCD) IIa. Linkage analysis and whole-exome sequencing identified a heterozygous germline frameshift mutation in the gene encoding nitrogen permease regulator-like 3 (NPRL3). NPRL3 is a component of GAP Activity Towards Rags 1, a negative regulator of the mammalian target of rapamycin complex 1 signaling pathway. Immunostaining of resected brain tissue demonstrated mammalian target of rapamycin activation. Screening of 52 unrelated individuals with FCD identified 2 additional patients with FCDIIa and germline NPRL3 mutations. Similar to DEPDC5, NPRL3 mutations may be considered as causal variants in patients with FCD or magnetic resonance imaging-negative focal epilepsy. PMID- 26285052 TI - A Minimum Spanning Forest-Based Method for Noninvasive Cancer Detection With Hyperspectral Imaging. AB - GOAL: The purpose of this paper is to develop a classification method that combines both spectral and spatial information for distinguishing cancer from healthy tissue on hyperspectral images in an animal model. METHODS: An automated algorithm based on a minimum spanning forest (MSF) and optimal band selection has been proposed to classify healthy and cancerous tissue on hyperspectral images. A support vector machine classifier is trained to create a pixel-wise classification probability map of cancerous and healthy tissue. This map is then used to identify markers that are used to compute mutual information for a range of bands in the hyperspectral image and thus select the optimal bands. An MSF is finally grown to segment the image using spatial and spectral information. CONCLUSION: The MSF based method with automatically selected bands proved to be accurate in determining the tumor boundary on hyperspectral images. SIGNIFICANCE: Hyperspectral imaging combined with the proposed classification technique has the potential to provide a noninvasive tool for cancer detection. PMID- 26285053 TI - Single-Trial ERP Component Analysis Using a Spatiotemporal LCMV Beamformer. AB - GOAL: For statistical analysis of event-related potentials (ERPs), there are convincing arguments against averaging across stimuli or subjects. Multivariate filters can be used to isolate an ERP component of interest without the averaging procedure. However, we would like to have certainty that the output of the filter accurately represents the component. METHODS: We extended the linearly constrained minimum variance (LCMV) beamformer, which is traditionally used as a spatial filter for source localization, to be a flexible spatiotemporal filter for estimating the amplitude of ERP components in sensor space. In a comparison study on both simulated and real data, we demonstrated the strengths and weaknesses of the beamformer as well as a range of supervised learning approaches. RESULTS: In the context of measuring the amplitude of a specific ERP component on a single-trial basis, we found that the spatiotemporal LCMV beamformer is a filter that accurately captures the component of interest, even in the presence of both structured noise (e.g., other overlapping ERP components) and unstructured noise (e.g., ongoing brain activity and sensor noise). CONCLUSION: The spatiotemporal LCMV beamformer method provides an accurate and intuitive way to conduct analysis of a known ERP component, without averaging across trials or subjects. SIGNIFICANCE: Eliminating averaging allows us to test more detailed hypotheses and apply more powerful statistical models. For example, it allows the usage of multilevel regression models that can incorporate between subject/stimulus variation as random effects, test multiple effects simultaneously, and control confounding effects by partial regression. PMID- 26285054 TI - Real-Time Patient-Specific ECG Classification by 1-D Convolutional Neural Networks. AB - GOAL: This paper presents a fast and accurate patient-specific electrocardiogram (ECG) classification and monitoring system. METHODS: An adaptive implementation of 1-D convolutional neural networks (CNNs) is inherently used to fuse the two major blocks of the ECG classification into a single learning body: feature extraction and classification. Therefore, for each patient, an individual and simple CNN will be trained by using relatively small common and patient-specific training data, and thus, such patient-specific feature extraction ability can further improve the classification performance. Since this also negates the necessity to extract hand-crafted manual features, once a dedicated CNN is trained for a particular patient, it can solely be used to classify possibly long ECG data stream in a fast and accurate manner or alternatively, such a solution can conveniently be used for real-time ECG monitoring and early alert system on a light-weight wearable device. RESULTS: The results over the MIT-BIH arrhythmia benchmark database demonstrate that the proposed solution achieves a superior classification performance than most of the state-of-the-art methods for the detection of ventricular ectopic beats and supraventricular ectopic beats. CONCLUSION: Besides the speed and computational efficiency achieved, once a dedicated CNN is trained for an individual patient, it can solely be used to classify his/her long ECG records such as Holter registers in a fast and accurate manner. SIGNIFICANCE: Due to its simple and parameter invariant nature, the proposed system is highly generic, and, thus, applicable to any ECG dataset. PMID- 26285055 TI - Numeric Investigation of Brain Tumor Influence on the Current Distributions During Transcranial Direct Current Stimulation. AB - This study constructed a series of high-resolution realistic human-head models with brain tumors, and numerically investigated the influence of brain tumor's location and grade on the current distributions, under different electrode montages during tDCS. The threshold area and the peak current density were also derived and analyzed in the region of interest. The simulation result showed that it is safe to apply tDCS on the patients with brain tumors to treat their neuropsychiatric conditions and cancer pain caused by the tumor; although considerable changes of the current distributions are induced by the presence of a brain tumor. In addition, several observations on the global and local influences of tumor grade and possible edema have been made as well. These findings should be helpful for researchers and clinical doctors to treat patients with brain tumors. This study is also the first numerical study to fill in the gap of tDCS applications on the patients with brain tumors. PMID- 26285056 TI - Collaboration is key: The actual experience of disciplines working together in child care. AB - Promoting young children's academic and developmental outcomes can no longer be achieved by the single efforts of one profession, but requires professionals to work together in inter-professional teams to understand the complexity of young children's lives. Collaboration in early childhood programs involves health professionals, educators, and other professionals sharing information, validating each other's roles, and providing input around which strategies promote positive outcomes for all children. There are, however, limited studies available within early childhood education on inter-disciplinary relationships between nurses and teachers. This paper helps to fill this void by exploring the relationship of an early childhood teacher and maternal and child health nurse working alongside one another in an Australian kindergarten. Through a narrative approach, a number of characteristics of the relationship were identified as key elements to a productive relationship. Findings are important for health professionals working with early childhood educators. By understanding the complexity within and between disciplines, professionals can work effectively to support young children and their families. PMID- 26285058 TI - Chemical analysis of constitutive pigmentation of human epidermis reveals constant eumelanin to pheomelanin ratio. AB - The skin constitutive pigmentation is given by the amount of melanin pigment, its relative composition (eu/pheomelanin) and distribution within the epidermis, and is largely responsible for the sensitivity to UV exposure. Nevertheless, a precise knowledge of melanins in human skin is lacking. We characterized the melanin content of human breast skin samples with variable pigmentations rigorously classified through the Individual Typology Angle (ITA) by image analysis, spectrophotometry after solubilization with Soluene-350 and high performance liquid chromatography (HPLC) after chemical degradation. ITA and total melanin content were found correlated, ITA and PTCA (degradation product of DHICA melanin), and TTCA (degradation product of benzothiazole-type pheomelanin) as well but not 4-AHP (degradation product of benzothiazine-type pheomelanin). Results revealed that human epidermis comprises approximately 74% of eumelanin and 26% pheomelanin, regardless of the degree of pigmentation. They also confirm the low content of photoprotective eumelanin among lighter skins thereby explaining the higher sensitivity toward UV exposure. PMID- 26285057 TI - Factors associated with false-negative cardiovascular magnetic resonance perfusion studies: A Clinical evaluation of magnetic resonance imaging in coronary artery disease (CE-MARC) substudy. AB - PURPOSE: To examine factors associated with false-negative cardiovascular magnetic resonance (MR) perfusion studies within the large prospective Clinical Evaluation of MR imaging in Coronary artery disease (CE-MARC) study population. Myocardial perfusion MR has excellent diagnostic accuracy to detect coronary heart disease (CHD). However, causes of false-negative MR perfusion studies are not well understood. MATERIALS AND METHODS: CE-MARC prospectively recruited patients with suspected CHD and mandated MR, myocardial perfusion scintigraphy, and invasive angiography. This subanalysis identified all patients with significant coronary stenosis by quantitative coronary angiography (QCA) and MR perfusion (1.5T, T1 -weighted gradient echo), using the original blinded image read. We explored patient and imaging characteristics related to false-negative or true-positive MR perfusion results, with reference to QCA. Multivariate regression analysis assessed the likelihood of false-negative MR perfusion according to four characteristics: poor image quality, triple-vessel disease, inadequate hemodynamic response to adenosine, and Duke jeopardy score (angiographic myocardium-at-risk score). RESULTS: In all, 265 (39%) patients had significant angiographic disease (mean age 62, 79% male). Thirty-five (5%) had false-negative and 230 (34%) true-positive MR perfusion. Poor MR perfusion image quality, triple-vessel disease, and inadequate hemodynamic response were similar between false-negative and true-positive groups (odds ratio, OR [95% confidence interval, CI]: 4.1 (0.82-21.0), P = 0.09; 1.2 (0.20-7.1), P = 0.85, and 1.6 (0.65 3.8), P = 0.31, respectively). Mean Duke jeopardy score was significantly lower in the false-negative group (2.6 +/- 1.7 vs. 5.4 +/- 3.0, OR 0.34 (0.21-0.53), P < 0.0001). CONCLUSION: False-negative cardiovascular MR perfusion studies are uncommon, and more common in patients with lower angiographic myocardium-at-risk. In CE-MARC, poor image quality, triple-vessel disease, and inadequate hemodynamic response were not significantly associated with false-negative MR perfusion. PMID- 26285059 TI - Antipsychotic drugs attenuate aberrant DNA methylation of DTNBP1 (dysbindin) promoter in saliva and post-mortem brain of patients with schizophrenia and Psychotic bipolar disorder. AB - Due to the lack of genetic association between individual genes and schizophrenia (SCZ) pathogenesis, the current consensus is to consider both genetic and epigenetic alterations. Here, we report the examination of DNA methylation status of DTNBP1 promoter region, one of the most credible candidate genes affected in SCZ, assayed in saliva and post-mortem brain samples. The Illumina DNA methylation profiling and bisulfite sequencing of representative samples were used to identify methylation status of the DTNBP1 promoter region. Quantitative methylation specific PCR (qMSP) was employed to assess methylation of DTNBP1 promoter CpGs flanking a SP1 binding site in the saliva of SCZ patients, their first-degree relatives and control subjects (30, 15, and 30/group, respectively) as well as in post-mortem brains of patients with SCZ and bipolar disorder (BD) versus controls (35/group). qRT-PCR was used to assess DTNBP1 expression. We found DNA hypermethylation of DTNBP1 promoter in the saliva of SCZ patients (~12.5%, P = 0.036), particularly in drug-naive patients (~20%, P = 0.011), and a trend toward hypermethylation in their first-degree relatives (P = 0.085) versus controls. Analysis of post-mortem brain samples revealed an inverse correlation between DTNBP1 methylation and expression, and normalization of this epigenetic change by classic antipsychotic drugs. Additionally, BD patients with psychotic depression exhibited higher degree of methylation versus other BD patients (~80%, P = 0.025). DTNBP1 promoter DNA methylation may become a key element in a panel of biomarkers for diagnosis, prevention, or therapy in SCZ and at risk individuals pending confirmatory studies with larger sample sizes to attain a higher degree of significance. PMID- 26285060 TI - The charm of "small data". PMID- 26285062 TI - Age-dependent loss of parvalbumin-expressing hippocampal interneurons in mice deficient in CHL1, a mental retardation and schizophrenia susceptibility gene. AB - In humans, deletions/mutations in the CHL1/CALL gene are associated with mental retardation and schizophrenia. Juvenile CHL1-deficient (CHL1(-/-) ) mice have been shown to display abnormally high numbers of parvalbumin-expressing (PV(+) ) hippocampal interneurons and, as adults, display behavioral traits observed in neuropsychiatric disorders. Here, we addressed the question whether inhibitory interneurons and synaptic plasticity in the CHL1(-/-) mouse are affected during brain maturation and in adulthood. We found that hippocampal, but not neocortical, PV(+) interneurons were reduced with age in CHL1(-/-) mice, from a surplus of +27% at 1 month to a deficit of -20% in adulthood compared with wild type littermates. This loss occurred during brain maturation, correlating with microgliosis and enhanced interleukin-6 expression. In parallel with the loss of PV(+) interneurons, the inhibitory input to adult CA1 pyramidal cells was reduced and a deficit in short- and long-term potentiation developed at CA3-CA1 excitatory synapses between 2 and 9 months of age in CHL1(-/-) mice. This deficit could be abrogated by a GABAA receptor agonist. We propose that region-specific aberrant GABAergic synaptic connectivity resulting from the mutation and a subsequently enhanced synaptic elimination during brain maturation lead to microgliosis, increase in pro-inflammatory cytokine levels, loss of interneurons, and impaired synaptic plasticity. Close homolog of L1-deficient (CHL1(-/-) ) mice have abnormally high numbers of parvalbumin (PV)-expressing hippocampal interneurons in juvenile animals, but in adult animals a loss of these cells is observed. This loss correlates with an increased density of microglia (M), enhanced interleukin-6 (IL6) production and a deficit in short- and long-term potentiation at CA3-CA1 excitatory synapses. Furthermore, adult CHL1(-/-) mice display behavioral traits similar to those observed in neuropsychiatric disorders of humans. PMID- 26285064 TI - Depot delivery of dexamethasone and cediranib for the treatment of brain tumor associated edema in an intracranial rat glioma model. AB - Treatments of brain tumor associated edema with systemically delivered dexamethasone, the standard of care, and cediranib, a novel anti-edema agent, are associated with systemic toxicities in brain tumor patients. A tunable, reservoir based drug delivery device was developed to investigate the effects of delivering dexamethasone and cediranib locally in the brain in an intracranial 9L gliosarcoma rat model. Reproducible, sustained releases of both dexamethasone and solid dispersion of cediranib in polyvinylpyrrolidone (AZD/PVP) from these devices were achieved. The water-soluble AZD/PVP, which exhibited similar bioactivity as cediranib, was developed to enhance the release of cediranib from the device. Local and systemic administration of both dexamethasone and cediranib was equally efficacious in alleviating edema but had no effect on tumor growth. Edema reduction led to modest but significant improvement in survival. Local delivery of dexamethasone prevented dexamethasone-induced weight loss, an adverse effect seen in animals treated with systemic dexamethasone. Local deliveries of dexamethasone and cediranib via these devices used only 2.36% and 0.21% of the systemic doses respectively, but achieved similar efficacy as systemic drug deliveries without the side effects associated with systemic administration. Other therapeutic agents targeting brain tumor can be delivered locally in the brain to provide similar improved treatment outcomes. PMID- 26285065 TI - Effect of Formaldehyde on the Heterogeneous Reaction of Nitrogen Dioxide on gamma Alumina. AB - Heterogeneous reactions of NO2 on various mineral aerosol particles have been investigated in many previous studies, but a fundamental understanding of how the adsorption of formaldehyde influences the heterogeneous reactions of NO2 remains unclear. In this work, the effect of formaldehyde preadsorption on heterogeneous reaction of NO2 on the surface of gamma-Al2O3 at 298 K and ambient pressure was investigated by using diffuse reflectance infrared Fourier transform spectrometry (DRIFTS). It was found that the preadsorption of HCHO on gamma-Al2O3 could suppress the formation of nitrate, and the rate of nitrate formation decreased with increasing amount of preadsorbed HCHO, whereas the following heterogeneous uptake of NO2 could suppress the hydration reaction of HCHO and promote the production of HCOO(-) during the reaction. Surface nitrite was formed and identified to be an intermediate product and gradually disappeared as the reaction proceeded. The amount of the formed nitrite decreased when the amount of HCHO increased. Uptake coefficients of heterogeneous reactions were calculated and found to be sensitive to the adsorption of HCHO. A possible mechanism for the influence of HCHO adsorption on the heterogeneous conversion of NO2 on gamma Al2O3 was proposed, and atmospheric implications based on these results were discussed. PMID- 26285061 TI - Alcohol and violence: neuropeptidergic modulation of monoamine systems. AB - Neurobiological processes underlying the epidemiologically established link between alcohol and several types of social, aggressive, and violent behavior remain poorly understood. Acute low doses of alcohol, as well as withdrawal from long-term alcohol use, may lead to escalated aggressive behavior in a subset of individuals. An urgent task will be to disentangle the host of interacting genetic and environmental risk factors in individuals who are predisposed to engage in escalated aggressive behavior. The modulation of 5-hydroxytryptamine impulse flow by gamma-aminobutyric acid (GABA) and glutamate, acting via distinct ionotropic and metabotropic receptor subtypes in the dorsal raphe nucleus during alcohol consumption, is of critical significance in the suppression and escalation of aggressive behavior. In anticipation and reaction to aggressive behavior, neuropeptides such as corticotropin-releasing factor, neuropeptide Y, opioid peptides, and vasopressin interact with monoamines, GABA, and glutamate to attenuate and amplify aggressive behavior in alcohol-consuming individuals. These neuromodulators represent novel molecular targets for intervention that await clinical validation. Intermittent episodes of brief social defeat during aggressive confrontations are sufficient to cause long-lasting neuroadaptations that can lead to the escalation of alcohol consumption. PMID- 26285063 TI - Nanoparticle modulation of the tumor microenvironment enhances therapeutic efficacy of cisplatin. AB - The tumor microenvironment (TME) serves as a multidrug resistant center for tumors under the assault of chemotherapy and a physiological barrier against the penetration of therapeutic nanoparticles (NPs). Previous studies have indicated the ability for therapeutic NP to distribute into, and deplete tumor-associated fibroblasts (TAFs) for improved therapeutic outcomes. However, a drug resistant phenotype gradually arises after repeated doses of chemotherapeutic NP. Herein, the acquisition of drug resistant phenotypes in the TME after repeated cisplatin NP treatment was examined. Particularly, this study was aimed at investigating the effects of NP damaged TAFs on neighboring cells and alteration of stromal structure after cisplatin treatment. Findings suggested that while off-targeted NP damaged TAFs and inhibited tumor growth after an initial dose, chronic exposure to cisplatin NP led to elevated secretion of Wnt16 in a paracrine manner in TAFs. Wnt16 upregulation was then attributed to heightened tumor cell resistance and stroma reconstruction. Results attest to the efficacy of Wnt16 knockdown in damaged TAFs as a promising combinatory strategy to improve efficacy of cisplatin NP in a stroma-rich bladder cancer model. PMID- 26285066 TI - Nerve excitability and structural changes in myelinated axons from diabetic mice. AB - OBJECTIVE: The mechanisms associated with nerve dysfunction and axonal loss in diabetes has not been fully clarified. Excitability and pathological aspects in nerves from diabetic mice were studied in order to explore the pathophysiology of diabetic neuropathy. METHODS: Myelinated nerve fibres from the sciatic nerve of BKS.Cg-m (+/+) Lepr (db) /J mice were studied by registering the CMAP controlled by an automated threshold tracking method. The sciatic nerve was also studied pathologically. RESULTS: Diabetic mice displayed longer latencies, higher thresholds and lower amplitudes compared to controls and had a rightward shift in the stimulus response curves. Strength-duration time constant was lower in diabetic mice but not reaching statistical significance (p=0.09). Diabetics displayed an increase in accommodation, with a smaller change in excitability in threshold electrotonus. Refractoriness, mean superexcitability and late subexcitability were reduced in diabetic mice. Diabetic mice had a larger number of myelinated fibres compared to controls (p<0.05), but larger than 9 MUm were virtually absent, accounting for near 7% in control animals. CONCLUSIONS: Db/db mice develop electrophysiological changes suggestive of membrane depolarization as the result of Na(+)/K(+) pump impairment. Loss of large myelinated fibres might also contribute to the nerve excitability profiles in this model. PMID- 26285067 TI - Quality of Life and Psychological Screening in Children with Type 1 Diabetes and their Mothers. AB - This study aimed to assess the levels of depression in children with type 1 diabetes mellitus (T1DM) and evaluate the quality of life as well as levels of depression and anxiety of their mothers.30 children with T1DM (mean age: 12.9+/ 2.9 years) and their mothers (mean age: 40.0+/-7.5 years) were included in the study. Control group consisted of 30 healthy children (mean age: 12.7+/-2.7 years) and their mothers (mean age: 39.8+/-7.2 years). The presence and severity of depressive symptoms in the children were evaluated using the Children's Depression Inventory (CDI). The short form 36-health survey (SF-36), the Beck Depression Inventory (BDI), and Spielberg's State-Trait Anxiety Inventory (STAI) were administered to all mothers.The children with T1DM had higher scores of depression compared to healthy children in the control group. The mothers of children with T1DM had significantly lower scores on all subscales of SF-36 except the bodily pain subscale. We observed a significant difference between groups in their BDI scores; the mean BDI score was higher in mothers of children with T1DM (p=0.004). There was a significant difference in STAI scores between groups. CDI scores positively correlated with the ages of and HgA1C levels in the children with T1DM. There was a positive correlation between CDI scores of children with T1DM and BDI scores of their mothers. In addition, CDI sores negatively correlated with the scores of vitality and social functioning subscales of SF-36.Our findings suggest screening for mental health issues and quality of life in diabetic children and their mothers. PMID- 26285068 TI - Rosiglitazone Attenuates Memory Impairment in Aged Rat with Diabetes by Inhibiting NF-kappa B Signal Pathway Activation. AB - Although the cognitive impairment in geriatric diabetes is common, its mechanisms remain unclear and therapies are limited. The present study investigated the effects of rosiglitazone on memory impairment in aged rats with diabetes. Diabetes was induced by streptozotocin in aged Wistar rats of 20-22 months. Then, the diabetic rats were divided randomly into the diabetic model group and rosiglitazone treatment group for assessment of cognitive function and cerebral injury at 8 weeks using Morris water maze (MWM) paradigm, real-time PCR and western blot analysis. Wistar rats of the same age were also assessed as control. In vitro, the therapeutic effect of rosiglitazone was investigated using rat chromaffin cell line PC12 cultured with high glucose and/or C-reactive protein (CRP). 8 weeks after diabetes induction aged rats exhibited marked and persistent hyperglycemia, weight loss, higher level of serum CRP and learning impairments. Enhanced cerebral inflammation in aged rats with diabetes was associated with over-activation of the nuclear factor kappaB (NF-kappaB) signalling pathway and upregulation of inflammatory cytokines (IL-6, TNFalpha) in the hippocampus. Compared with the diabetic group, level of serum CRP, inflammatory cytokines and over-activation of NF-kappaB signalling pathway in the hippocampus were restored partially concomitant with attenuation of cognitive dysfunction indicated as markedly decreased escape latency and distance during MWM test in the rosiglitazone treatment group. In vitro, high glucose significantly activated NF kappaB signalling pathway and upregulated inflammatory cytokines. CRP synergistically promoted high glucose-mediated effects. Rosiglitazone significantly ameliorated the effects mediated by high glucose and CRP.These effects were significantly reversed by co-treatment with the PPARgamma antagonist T0070907. These results suggest that rosiglitazone can improve cognitive function in aged rats with diabetes by inhibiting the NF-kappaB signal activation and decreasing the expressions of inflammatory cytokines in the hippocampus. PMID- 26285069 TI - Short-term Regulation of Resistin in vivo by Oral Lipid Ingestion and in vitro by Fatty Acid Stimulation. AB - BACKGROUND AND AIM: Dysbalance of pro- and anti-inflammatory adipokines is a hallmark of metabolic syndrome but their nutrition-dependent regulation in healthy individuals is poorly characterized. We investigated pro-inflammatory resistin and anti-inflammatory adiponectin regulation during oral lipid ingestion (OLI) in healthy adults. Response of resistin upon free fatty acid (FFA) stimulation was investigated in 3T3-L1 adipocytes. MATERIAL AND METHODS: 100 healthy volunteers underwent OLI. Venous blood was drawn after 0, 2, 4, and 6 hours (h). Subjects were characterized by anthropometric and standard laboratory parameters. Serum concentrations of adiponectin and resistin were measured by enzyme-linked immunosorbent assay (ELISA). Adipocytes were stimulated with FFA and concentrations of adipokines were measured by ELISA. RESULTS: Irrespective of BMI and gender, OLI led to a significant reduction of resistin serum levels in a stepwise manner whereas adiponectin concentrations remained unchanged. There were positive correlations of resistin with waist/hip ratio and visfatin levels, as was calculated by regression analysis. Resistin concentrations were significantly higher in smokers when compared to non-smokers. Adiponectin concentrations were higher in females and in users of hormonal contraception. Adiponectin levels showed a positive correlation with heart rate and HDL cholesterol and a negative correlation with age, waist/hip-ratio, BMI, diastolic/systolic blood pressure, visfatin levels and LDL/HDL-ratio. Resistin secretion was significantly induced by palmitic acid, linoleic acid and oleic acid in adipocytes. CONCLUSIONS: OLI is a physiological repressor of systemic resistin release whereas FFA upregulate resistin release in vitro from adipocytes. PMID- 26285070 TI - Gender-specific Effects of Treatment with Lifestyle, Metformin or Sulfonylurea on Glycemic Control and Body Weight: A German Multicenter Analysis on 9 108 Patients. AB - Effects of diabetes treatment are strongly connected to individual factors, but the relevant role of gender has not been addressed so far. This observational study evaluates whether monotherapy with lifestyle, metformin or sulfonylurea has gender-specific effects on glycemic control and/or body weight. Data of 9 108 patients with type 2 diabetes from 129 German diabetes centers were assessed by a standardized, prospective, computer-based diabetes care and outcome documentation system (DPV-Wiss-database; age 63.1+/-12.8 years, diabetes duration 5.7+/-7.4 years, HbA1c 55+/-17.7 mmol/mol [7.2+/-1.6%], BMI 30.6+/-6.1 kg/m(2), 49.3% female patients). Antidiabetic concepts included lifestyle intervention (n=5,787), metformin (n=2,180), sulfonylurea (n=943) or other antidiabetic drugs (n=198), respectively. HbA1c and body weight were compared before and after a stable monotherapeutical period of 0.8+/-0.4 years. Women had a significantly higher reduction of body weight after treatment with lifestyle (women-0.8+/-0.1 vs. men-0.2+/-0.1 kg; p<0.05), metformin (women-1.8+/-0.2 vs. men-1.2+/-0.2 kg; p<0.05) or sulfonylurea drugs (women-0.9+/-0.2 vs. men - 0.1+/-0.2 kg; p<0.05), whereas men displayed significantly higher HbA1c-reductions after treatment with lifestyle (women-6.9+/-0.2 mmol/mol [- 0.6+/-0.02%] vs. men-7.5+/-0.2 mmol/mol [0.7+/-0.02%]; p<0.05) and metformin only (women-6.3+/-0.3 mmol/mol [- 0.6+/ 0.03%] vs. men - 7.4+/-0.3 mmol/mol [- 0.7+/-0.03%]; p<0.05). No differences were seen for sulfonylurea monotherapy concerning the HbA1c-reduction (women - 5.6+/ 0.5 mmol/mol [- 0.5+/-0.05%] vs. men-6.4+/-0.4 mmol/mol [- 0.6+/-0.04%]; p=0.196). In summary, antidiabetic treatment concepts might result in gender specific effects on body weight and HbA1c. Gender might therefore represent another important factor in the context of an individualized treatment management of type 2 diabetes. PMID- 26285071 TI - Hemostatic Disorders in Hormonally Active Pituitary Tumors. AB - Endocrinopathies encompass heterogeneous diseases that can lead to hemostasis disorders at various stages over their clinical course. Normal hemostasis requires an equilibrium between the processes of coagulation and fibrinolysis, which depend on multiple activators and inhibitors. To date, the influence of various hormonal disorders on the hemostatic system has been assessed many times. The aim of this review was to analyze hemostasis abnormalities that occur in patients with hormonally active pituitary tumors: corticotropinoma, somatotropinoma, prolactinoma, gonadotropinoma and thyrotropinoma. Authors discuss studies that examined coagulation and hemostasis parameters among patients with these tumors, as well as analyze antithrombotic prophylaxis approach for endogenous hypercortisolemia subjects in particular. PMID- 26285073 TI - Ureteral Myxolipoma. PMID- 26285075 TI - Modification of cut-off values for HE4, CA125 and the ROMA algorithm for early stage epithelial ovarian cancer detection: Results from 1021 cases in South China. AB - OBJECTIVES: The purpose of this study was to evaluate the performance of human epididymis protein 4 (HE4) and the Risk of Ovarian Malignancy Algorithm (ROMA) in early stage epithelial ovarian cancer (EOC) detection in patients in southern China. Additionally, this study proposes a possible ideal cut-off value for each marker to its own population in South China. DESIGN AND METHODS: Serum HE4 and CA125 were measured in 756 patients with pelvic masses (275 malignancies, 53 borderline tumors and 428 benign diseases), and their ROMA values were calculated. Areas under the receiver operator characteristic (ROC) curves (AUC) were assessed for HE4, CA125, ROMA and combinations of these biomarkers. RESULTS: Both HE4 and ROMA performed better diagnostically than CA125 alone for early stage EOC, with AUCs ranging from 0.714 for HE4, 0.699 for ROMA, and 0.463 for CA125 in premenopausal subjects, and 0.902 for ROMA, 0.880 for HE4, and 0.256 for CA125 in postmenopausal subjects. CONCLUSIONS: HE4 and ROMA alone were found to be better than CA125 for detecting borderline tumors and early-stage EOC. The optimal cut-off values (HE4: 70pmol/l for all; CA125: 60U/ml for pre- and 35U/ml for postmenopausal women) could notably improve diagnostic performance in EOC detection in patients in southern China. PMID- 26285074 TI - Multi-center evaluation of a user-friendly lateral flow assay to determine IP-10 and CCL4 levels in blood of TB and non-TB cases in Africa. AB - OBJECTIVE: Multi-center evaluation of a user-friendly lateral flow test for detection of IP-10 and CCL4 levels in Mycobacterium tuberculosis (Mtb) antigen stimulated whole blood samples from tuberculosis (TB) suspects. DESIGN AND METHODS: A quantitative lateral flow (LF)-based assay platform was applied to detect chemokines IP-10 and CCL4. Chemokine quantitation was achieved using interference-free, fluorescent up-converting phosphor (UCP) labels. The new assays allowed worldwide shipping and storage without requiring a cold chain and were tested at seven institutes (including Ethiopia, Malawi, The Gambia, South Africa, Uganda and Namibia) employing portable lightweight readers for detection of the UCP label. At each site, clinical samples, confirmed TB and non-TB (i.e. other respiratory diseases (ORD)) cases, were collected and analyzed simultaneously with quality control (QC) human IP-10 or CCL4 standards. RESULTS: Performance of the UCP-LF assay in Africa using QC standards indicated high robustness allowing quantitative detection between 100 and 100,000pg/mL. The optimized assays allowed successful determination of chemokine levels using 1MUL whole blood sample from the locally recruited subjects with TB or ORD. CONCLUSION: This African multi-center trial further demonstrated the applicability of the low-tech and robust UCP-LF platform as a convenient quantitative assay for chemokine detection in whole blood. Ambient shipping and storage of all assay reagents and the availability of lightweight standalone readers were acknowledged as essential requirement for test implementation in particular in remote and resource-limited settings. PMID- 26285076 TI - Doping Level of Boron-Doped Diamond Electrodes Controls the Grafting Density of Functional Groups for DNA Assays. AB - The impact of different doping levels of boron-doped diamond on the surface functionalization was investigated by means of electrochemical reduction of aryldiazonium salts. The grafting efficiency of 4-nitrophenyl groups increased with the boron levels (B/C ratio from 0 to 20,000 ppm). Controlled grafting of nitrophenyldiazonium was used to adjust the amount of immobilized single-stranded DNA strands at the surface and further on the hybridization yield in dependence on the boron doping level. The grafted nitro functions were electrochemically reduced to the amine moieties. Subsequent functionalization with a succinic acid introduced carboxyl groups for subsequent binding of an amino-terminated DNA probe. DNA hybridization significantly depends on the probe density which is in turn dependent on the boron doping level. The proposed approach opens new insights for the design and control of doped diamond surface functionalization for the construction of DNA hybridization assays. PMID- 26285072 TI - Oxidative stress in beta-thalassaemia and sickle cell disease. AB - Sickle cell disease and beta-thalassaemia are inherited haemoglobinopathies resulting in structural and quantitative changes in the beta-globin chain. These changes lead to instability of the generated haemoglobin or to globin chain imbalance, which in turn impact the oxidative environment both intracellularly and extracellularly. The ensuing oxidative stress and the inability of the body to adequately overcome it are, to a large extent, responsible for the pathophysiology of these diseases. This article provides an overview of the main players and control mechanisms involved in the establishment of oxidative stress in these haemoglobinopathies. PMID- 26285077 TI - Comments and controversies: Piecing together the neurobiology of decision-making. AB - In this paper, we address issues raised by Tierney and Hart (Assessing Complex Cognitive Functioning Requires Multiple Tasks) in response to our recently published findings showing that less advantageous decision-making on the Iowa Gambling Task (IGT) was associated with enhanced right ventral striatal dopamine response to intravenous amphetamine (Oswald et al., 2015). We agree with the overall premise of the paper, which was that decision-making involves multiple components, which may not be tapped by a single measure. While Tierney and Hart also bring up some important issues related to the construct validity of the IGT, we suggest that they are failing to put the findings within the context of the growing body of research that has highlighted the role of DA function in risk taking behavior across species using a variety of tasks. It should also be noted that it was not our goal to "cover all bases" within the context of a single study. Nevertheless, we appreciate the discussion, which we believe highlights the need for further empirical refinement of the construct to facilitate detection and understanding of the differential role that specific molecular mechanisms may play in the component processes. PMID- 26285078 TI - Depressive symptomatology should be systematically controlled for in neuroticism research. PMID- 26285079 TI - The functional significance of EEG microstates--Associations with modalities of thinking. AB - The momentary, global functional state of the brain is reflected by its electric field configuration. Cluster analytical approaches consistently extracted four head-surface brain electric field configurations that optimally explain the variance of their changes across time in spontaneous EEG recordings. These four configurations are referred to as EEG microstate classes A, B, C, and D and have been associated with verbal/phonological, visual, subjective interoceptive autonomic processing, and attention reorientation, respectively. The present study tested these associations via an intra-individual and inter-individual analysis approach. The intra-individual approach tested the effect of task induced increased modality-specific processing on EEG microstate parameters. The inter-individual approach tested the effect of personal modality-specific parameters on EEG microstate parameters. We obtained multichannel EEG from 61 healthy, right-handed, male students during four eyes-closed conditions: object visualization, spatial-visualization, verbalization (6 runs each), and resting (7 runs). After each run, we assessed participants' degrees of object-visual, spatial-visual, and verbal thinking using subjective reports. Before and after the recording, we assessed modality-specific cognitive abilities and styles using nine cognitive tests and two questionnaires. The EEG of all participants, conditions, and runs was clustered into four classes of EEG microstates (A, B, C, and D). RMANOVAs, ANOVAs and post-hoc paired t-tests compared microstate parameters between conditions. TANOVAs compared microstate class topographies between conditions. Differences were localized using eLORETA. Pearson correlations assessed interrelationships between personal modality-specific parameters and EEG microstate parameters during no-task resting. As hypothesized, verbal as opposed to visual conditions consistently affected the duration, occurrence, and coverage of microstate classes A and B. Contrary to associations suggested by previous reports, parameters were increased for class A during visualization, and class B during verbalization. In line with previous reports, microstate D parameters were increased during no-task resting compared to the three internal, goal-directed tasks. Topographic differences between conditions included particular sub-regions of components of the metabolic default mode network. Modality-specific personal parameters did not consistently correlate with microstate parameters except verbal cognitive style which correlated negatively with microstate class A duration and positively with class C occurrence. This is the first study that aimed to induce EEG microstate class parameter changes based on their hypothesized functional significance. Beyond the associations of microstate classes A and B with visual and verbal processing, respectively, our results suggest that a finely-tuned interplay between all four EEG microstate classes is necessary for the continuous formation of visual and verbal thoughts. Our results point to the possibility that the EEG microstate classes may represent the head-surface measured activity of intra-cortical sources primarily exhibiting inhibitory functions. However, additional studies are needed to verify and elaborate on this hypothesis. PMID- 26285080 TI - Palladium(II)-Catalyzed Direct C-H Alkenylation of Thienothiophene and Related Fused Heteroarenes. AB - The palladium-catalyzed direct alkenylation of thieno[3,2-b]thiophene takes place regioselectively at C2. Symmetrically and unsymmetrically 2,5-dialkenylated thienothiophene derivatives can be prepared by the catalytic procedure. Related fused thienyl and carbazole derivatives also undergo regioselective direct alkenylation. PMID- 26285081 TI - Statistical Considerations When Assessing Short Latency Stretch Reflexes in the Human Soleus Muscle. AB - The aim was to investigate trial-by-trial response characteristics in the short latency stretch reflex (SSR). Fourteen dorsiflexion stretches were applied to the ankle joint with a precontracted soleus muscle on 2 days. The magnitude and variability of trial-by-trial responses of the SSR were assessed. The SSR was log normally distributed and variance heterogeneous between subjects. For some subjects, the magnitude and variance differed between days and stretches. As velocity increased, variance heterogeneity tended to decrease and response magnitude increased. The current study demonstrates the need to assess trial-by trial response characteristics and not averaged curves. Moreover, it provides an analysis of SSR characteristics accounting for log-normally distributed and variance heterogeneous trial-by-trial responses. PMID- 26285082 TI - Direct hippocampal injection of pseudo lentivirus-delivered nerve growth factor gene rescues the damaged cognitive function after traumatic brain injury in the rat. AB - Traumatic brain injury (TBI) treatment is a long-term process and requires repeated medicine administration, which, however, can cause high expense, infection, and hemorrhage to patients. To investigate how a long-term expression of nerve growth factor (Ngf) gene affects the injured hippocampus function post TBI, in this study, a pseudo lentivirus carrying the beta-Ngf fusion gene, with green fluorescence protein (GFP) gene, was constructed to show the gene expression and its ability of protecting cells from oxidative damage in vitro. Then, the pseudo lentivirus-carried beta-Ngf fusion gene was directly injected into the injured brain to evaluate its influence on the injured hippocampus function post-TBI in vivo. We found that the expression of the pseudo lentivirus delivered beta-Ngf fusion gene lasted more than four-week after the cell transduction and the encoded beta-NGF fusion protein could induce the neuron-like PC12 cell differentiation. Moreover, the hippocampal injection of the pseudo lentivirus-carried beta-Ngf fusion gene sped the injured cognitive function recovery of the rat subjected to TBI. Together, our findings indicate that the long-term expression of the beta-Ngf fusion gene, delivered by the pseudo lentivirus, can promote the neurite outgrowth of the neuron-like cells and protect the cells from the oxidative damage in vitro, and that the direct and single dose hippocampal injection of the pseudo lentivirus-carried beta-Ngf fusion gene is able to rescue the hippocampus function after the TBI in the rat. PMID- 26285083 TI - Bio-inspired configurable multiscale extracellular matrix-like structures for functional alignment and guided orientation of cells. AB - Inspired by the hierarchically organized protein fibers in extracellular matrix (ECM) as well as the physiological importance of multiscale topography, we developed a simple but robust method for the design and manipulation of precisely controllable multiscale hierarchical structures using capillary force lithography in combination with an original wrinkling technique. In this study, based on our proposed fabrication technology, we approached a conceptual platform that can mimic the hierarchically multiscale topographical and orientation cues of the ECM for controlling cell structure and function. We patterned the polyurethane acrylate-based nanotopography with various orientations on the microgrooves, which could provide multiscale topography signals of ECM to control single and multicellular morphology and orientation with precision. Using our platforms, we found that the structures and orientations of fibroblast cells were greatly influenced by the nanotopography, rather than the microtopography. We also proposed a new approach that enables the generation of native ECM having nanofibers in specific three-dimensional (3D) configurations by culturing fibroblast cells on the multiscale substrata. We suggest that our methodology could be used as efficient strategies for the design and manipulation of various functional platforms, including well-defined 3D tissue structures for advanced regenerative medicine applications. PMID- 26285085 TI - Two-Dimensional CaIn2S4/g-C3N4 Heterojunction Nanocomposite with Enhanced Visible Light Photocatalytic Activities: Interfacial Engineering and Mechanism Insight. AB - Design and exploitation of efficient visible light photocatalytic systems for water splitting and degradation of organic dyes are of huge interest in the fields of energy conversion and environmental protection. Herein, two-dimensional CaIn2S4/g-C3N4 heterojunction nanocomposites with intimate interfacial contact have been synthesized by a facile two-step method. Compared with pristine g-C3N4 and CaIn2S4, the CaIn2S4/g-C3N4 heterojunction nanocomposites exhibited significantly enhanced H2 evolution and photocatalytic degradation of methyl orange (MO) activities under visible light irradiation. The optimal CaIn2S4/g C3N4 nanocomposite shows a H2 evolution rate of 102 MUmol g(-1) h(-1), which is more than 3 times that of pristine CaIn2S4. The mechanisms for improving the photocatalytic performance of the CaIn2S4/g-C3N4 nanocomposites were proposed by using the photoluminescence measurement and electrochemical analyses. It was demonstrated that the enhanced photocatalytic performance of CaIn2S4/g-C3N4 heterojunction nanocomposites mainly stems from the enhanced charge separation efficiency. In addition, a plausible mechanism for the degradation of MO dye over CaIn2S4/g-C3N4 nanocomposites is also elucidated using active species scavenger's studies. PMID- 26285084 TI - Geometric guidance of integrin mediated traction stress during stem cell differentiation. AB - Cells sense and transduce the chemical and mechanical properties of their microenvironment through cell surface integrin receptors. Traction stress exerted by cells on the extracellular matrix mediates focal adhesion stabilization and regulation of the cytoskeleton for directing biological activity. Understanding how stem cells integrate biomaterials properties through focal adhesions during differentiation is important for the design of soft materials for regenerative medicine. In this paper we use micropatterned hydrogels containing fluorescent beads to explore force transmission through integrins from single mesenchymal stem cells (MSCs) during differentiation. When cultured on polyacrylamide gels, MSCs will express markers associated with osteogenesis and myogenesis in a stiffness dependent manner. The shape of single cells and the composition of tethered matrix protein both influence the magnitude of traction stress applied and the resultant differentiation outcome. We show how geometry guides the spatial positioning of focal adhesions to maximize interaction with the matrix, and uncover a relationship between alphavbeta3, alpha5beta1 and mechanochemical regulation of osteogenesis. PMID- 26285086 TI - A Self-Cleaning TiO2 Nanosisal-like Coating toward Disposing Nanobiochips of Cancer Detection. AB - The advanced nanobiochips have been widely employed in diagnosing some high incidence of diseases because of their portable, low-cost, and highly sensitive features. However, the subsequent disposal of these wastes remains unexposed, probably giving rise to serious environmental pollution and health risks similar to traditional biomedical waste. Here, we have presented a TiO2 nanosisal-like coating for disposing nanobiochip waste via the photoresponsive self-cleaning features of the nanobiochip, demonstrated by the nanochips of cancer detection. Moreover, the high specificity and sensitivity of nanochips can be maintained by integrating unique nanostructured coatings (i.e., nanosisal-like coating) with specific recognition molecules (i.e., anti-EpCAM). Therefore, this study will provide a promising strategy for the design and management of practical nanobiodevices, thereby eliminating the old path "pollute first, clean up later". PMID- 26285087 TI - Inhomogeneity of methane emissions from a dairy waste lagoon. AB - Methane (CH4) is the dominant greenhouse gas emitted by animal agriculture manure. Since the gas is relatively insoluble in water, it is concentrated in discrete bubbles that rise through waste lagoons and burst at the surface. This results in lagoon emissions that are inhomogeneous in both space and time. Emissions from a midwestern dairy waste lagoon were measured over 2 weeks to evaluate the spatial homogeneity of the source emissions and to compare two methods for measuring this inhomogeneous emission. Emissions were determined using an inverse dispersion model based on CH4 concentrations measured both by a single scanning tunable diode laser (TDL) aimed at a series of reflectors and by flame ionization detection (FID) gas chromatography on line-sampled air. Emissions were best estimated using scanned TDL concentrations over relatively short optical paths that collectively span the entire cross-wind width of the source, so as to provide both the best capture of discrete plumes from the bursting bubbles on the lagoon surface and the best detection of CH4 background concentrations. The lagoon emissions during the study were spatially inhomogeneous at hourly time scales. Partitioning the inhomogeneous source into two source regions reduced the estimated emissions of the overall lagoon by 57% but increased the variability. Consequently, it is important to assess the homogeneity of a source prior to measurements and final emissions calculation. IMPLICATIONS: Plans for measuring methane emissions from waste lagoons must take into account the spatial inhomogeneity of the source strength. The assumption of emission source homogeneity for a low-solubility gas such as CH4 emitted from an animal waste lagoon can result in significant emission overestimates. The entire breadth and length of the area source must be measured, preferably with multiple optical paths, for the detection of discrete plumes from the different emitting regions and for determining the background concentration. Other gases with similarly poor solubility in water may also require partitioning of the lagoon source area. PMID- 26285088 TI - Dynamic Postural-Stability Deficits After Cryotherapy to the Ankle Joint. AB - CONTEXT: Decreased postural stability is a primary risk factor for lower limb musculoskeletal injuries. During athletic competitions, cryotherapy may be applied during short breaks in play or during half-time; however, its effects on postural stability remain unclear. OBJECTIVE: To investigate the acute effects of a 15-minute ankle-joint cryotherapy application on dynamic postural stability. DESIGN: Controlled laboratory study. SETTING: University biomechanics laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 29 elite-level collegiate male field sport athletes (age = 20.8 +/- 1.12 years, height = 1.80 +/- 0.06 m, mass = 81.89 +/- 8.59 kg) participated. INTERVENTION(S): Participants were tested on the anterior (ANT), posterolateral (PL), and posteromedial (PM) reach directions of the Star Excursion Balance Test before and after a 15-minute ankle-joint cryotherapy application. MAIN OUTCOME MEASURE(S): Normalized reach distances; sagittal-plane kinematics of the hip, knee, and ankle joints; and associated mean velocity of the center-of-pressure path during performance of the ANT, PL, and PM reach directions of the Star Excursion Balance Test. RESULTS: We observed a decrease in reach-distance scores for the ANT, PL, and PM reach directions from precryotherapy to postcryotherapy (P < .05). No differences were observed in hip , knee-, or ankle-joint sagittal-plane kinematics (P > .05). We noted a decrease in mean velocity of the center-of-pressure path from precryotherapy to postcryotherapy (P < .05) in all reach directions. CONCLUSIONS: Dynamic postural stability was adversely affected immediately after cryotherapy to the ankle joint. PMID- 26285089 TI - Anticipatory Effects on Lower Extremity Neuromechanics During a Cutting Task. AB - CONTEXT: Continued research into the mechanism of noncontact anterior cruciate ligament injury helps to improve clinical interventions and injury-prevention strategies. A better understanding of the effects of anticipation on landing neuromechanics may benefit training interventions. OBJECTIVE: To determine the effects of anticipation on lower extremity neuromechanics during a single-legged land-and-cut task. DESIGN: Controlled laboratory study. SETTING: University biomechanics laboratory. PARTICIPANTS: Eighteen female National Collegiate Athletic Association Division I collegiate soccer players (age = 19.7 +/- 0.8 years, height = 167.3 +/- 6.0 cm, mass = 66.1 +/- 2.1 kg). INTERVENTION(S): Participants performed a single-legged land-and-cut task under anticipated and unanticipated conditions. MAIN OUTCOME MEASURE(S): Three-dimensional initial contact angles, peak joint angles, and peak internal joint moments and peak vertical ground reaction forces and sagittal-plane energy absorption of the 3 lower extremity joints; muscle activation of selected hip- and knee-joint muscles. RESULTS: Unanticipated cuts resulted in less knee flexion at initial contact and greater ankle toe-in displacement. Unanticipated cuts were also characterized by greater internal hip-abductor and external-rotator moments and smaller internal knee-extensor and external-rotator moments. Muscle-activation profiles during unanticipated cuts were associated with greater activation of the gluteus maximus during the precontact and landing phases. CONCLUSIONS: Performing a cutting task under unanticipated conditions changed lower extremity neuromechanics compared with anticipated conditions. Most of the observed changes in lower extremity neuromechanics indicated the adoption of a hip-focused strategy during the unanticipated condition. PMID- 26285090 TI - Lower Extremity Landing Biomechanics in Both Sexes After a Functional Exercise Protocol. AB - CONTEXT: Sex differences in landing biomechanics play a role in increased rates of anterior cruciate ligament (ACL) injuries in female athletes. Exercising to various states of fatigue may negatively affect landing mechanics, resulting in a higher injury risk, but research is inconclusive regarding sex differences in response to fatigue. OBJECTIVE: To use the Landing Error Scoring System (LESS), a valid clinical movement-analysis tool, to determine the effects of exercise on the landing biomechanics of males and females. DESIGN: Cross-sectional study. SETTING: University laboratory. PATIENTS OR OTHER PARTICIPANTS: Thirty-six (18 men, 18 women) healthy college-aged athletes (members of varsity, club, or intramural teams) with no history of ACL injury or prior participation in an ACL injury-prevention program. INTERVENTION(S): Participants were videotaped performing 3 jump-landing trials before and after performance of a functional, sportlike exercise protocol consisting of repetitive sprinting, jumping, and cutting tasks. MAIN OUTCOME MEASURE(S): Landing technique was evaluated using the LESS. A higher LESS score indicates more errors. The mean of the 3 LESS scores in each condition (pre-exercise and postexercise) was used for statistical analysis. RESULTS: Women scored higher on the LESS (6.3 +/- 1.9) than men (5.0 +/- 2.3) regardless of time (P = .04). Postexercise scores (6.3 +/- 2.1) were higher than preexercise scores (5.0 +/- 2.1) for both sexes (P = .01), but women were not affected to a greater degree than men (P = .62). CONCLUSIONS: As evidenced by their higher LESS scores, females demonstrated more errors in landing technique than males, which may contribute to their increased rate of ACL injury. Both sexes displayed poor technique after the exercise protocol, which may indicate that participants experience a higher risk of ACL injury in the presence of fatigue. PMID- 26285091 TI - National Athletic Trainers' Association Position Statement: Exertional Heat Illnesses. AB - OBJECTIVE: To present best-practice recommendations for the prevention, recognition, and treatment of exertional heat illnesses (EHIs) and to describe the relevant physiology of thermoregulation. BACKGROUND: Certified athletic trainers recognize and treat athletes with EHIs, often in high-risk environments. Although the proper recognition and successful treatment strategies are well documented, EHIs continue to plague athletes, and exertional heat stroke remains one of the leading causes of sudden death during sport. The recommendations presented in this document provide athletic trainers and allied health providers with an integrated scientific and clinically applicable approach to the prevention, recognition, treatment, and return-to-activity guidelines for EHIs. These recommendations are given so that proper recognition and treatment can be accomplished in order to maximize the safety and performance of athletes. RECOMMENDATIONS: Athletic trainers and other allied health care professionals should use these recommendations to establish onsite emergency action plans for their venues and athletes. The primary goal of athlete safety is addressed through the appropriate prevention strategies, proper recognition tactics, and effective treatment plans for EHIs. Athletic trainers and other allied health care professionals must be properly educated and prepared to respond in an expedient manner to alleviate symptoms and minimize the morbidity and mortality associated with these illnesses. PMID- 26285094 TI - Dental Materials, Instruments, and Devices. PMID- 26285095 TI - Anatomic Analysis of the Maxillary Sinus: Preliminary Morphologic Comparison of Animal Models (Pig, Lamb, and Human). PMID- 26285093 TI - Genome-wide analysis of esterase-like genes in the striped rice stem borer, Chilo suppressalis. AB - The striped rice stem borer, Chilo suppressalis, a destructive pest of rice, has developed high levels of resistance to certain insecticides. Esterases are reported to be involved in insecticide resistance in several insects. Therefore, this study systematically analyzed esterase-like genes in C. suppressalis. Fifty one esterase-like genes were identified in the draft genomic sequences of the species, and 20 cDNA sequences were derived which encoded full- or nearly full length proteins. The putative esterase proteins derived from these full-length genes are overall highly diversified. However, key residues that are functionally important including the serine residue in the active site are conserved in 18 out of the 20 proteins. Phylogenetic analysis revealed that most of these genes have homologues in other lepidoptera insects. Genes CsuEst6, CsuEst10, CsuEst11, and CsuEst51 were induced by the insecticide triazophos, and genes CsuEst9, CsuEst11, CsuEst14, and CsuEst51 were induced by the insecticide chlorantraniliprole. Our results provide a foundation for future studies of insecticide resistance in C. suppressalis and for comparative research with esterase genes from other insect species. PMID- 26285096 TI - Developmental Dyslexia With and Without Language Impairment: ERPs Reveal Qualitative Differences in Morphosyntactic Processing. AB - This study aimed to characterize neuropsychological and linguistic skills in children with Developmental Dyslexia (DD) with and without Language Impairment (LI). Behavioral tests of short-term memory, phonemic awareness, and morphosyntactic processing and electrophysiological responses to agreement violations were administered to 32 DD children (16 with additional LI) and 16 controls. Behavioral data revealed quantitative differences among groups: DD+LI children showed the worst performance, followed by DD-only children and controls. Event-related potential results confirmed atypical morphosyntactic processing in the DD-only group, highlighting qualitative differences between groups. These results support multifactor models of learning disabilities, where different patterns of deficits characterize different subgroups. PMID- 26285097 TI - Behavioral Laterality and Aging: The Free-Recall Dichotic-Listening Right-Ear Advantage Increases With Age. AB - The effect of aging on brain asymmetry was studied under consideration of possible confounding effects of known age-related decline in higher cognitive functioning. In a sample of 3,680 participants aged 20-79 years, laterality was assessed with a verbal, free-recall dichotic-listening paradigm with one stimulus pair presentation per trial, minimizing working-memory and cognitive-control demands during task performance. Laterality, reflected as right-ear preference for dichotic stimuli, was found to be increased in older age (above 60 years). This effect was due to a reduced report of left-ear stimuli, while the report of right-ear stimuli stayed on comparable levels across all ages. PMID- 26285099 TI - Isolation of Brucella ceti from a Long-finned Pilot Whale (Globicephala melas) and a Sowerby's Beaked Whale (Mesoploden bidens). AB - Brucella ceti is an emerging zoonotic pathogen that has been recovered from several species of cetaceans in the world's oceans over the past 20 yr. We report the recovery of B. ceti from a Sowerby's beaked whale (Mesoploden bidens) and a long-finned pilot whale (Globicehala melas). Recovery from the testis of a long finned pilot whale provides further evidence of potential for B. ceti infection to impact the reproductive success of cetaceans, many of which are threatened species. The addition of another two cetacean species to the growing number from which B. ceti has been recovered also further emphasizes the concern for human infections with this organism. PMID- 26285098 TI - Differentiation of ICOS+ and ICOS- recent thymic emigrant regulatory T cells (RTE T regs) during normal pregnancy, pre-eclampsia and HELLP syndrome. AB - Two different subsets of naturally occurring regulatory T cells (nTregs), defined by their expression of the inducible co-stimulatory (ICOS) molecule, are produced by the human thymus. To examine the differentiation of ICOS(+) and ICOS(-) CD45RA(+) CD31(+) recent thymic emigrant (RTE) T regs during normal pregnancy and in the presence of pre-eclampsia or haemolysis elevated liver enzymes low platelet (HELLP)-syndrome, we used six-colour flow cytometric analysis to determine the changes in the composition of the ICOS(+) and ICOS(-) T reg pools with CD45RA(+) CD31(+) RTE T regs, CD45RA(+) CD31(-) mature naive (MN) T regs, CD45RA(-) CD31(+) and CD45RA(-) CD31(-) memory Tregs. With the beginning of pregnancy until term, we observed a strong differentiation of both ICOS(+) and ICOS(-) CD45RA(+) CD31(+) RTE, but not CD45RA(+) CD31(-) MN T regs, into CD45RA( ) CD31(-) memory T regs. At the end of pregnancy, the onset of spontaneous term labour was associated with a significant breakdown of ICOS(+) CD45RA(-) CD31(-) memory T regs. However, in the presence of pre-eclampsia, there was a significantly increased differentiation of ICOS(+) and ICOS(-) CD45RA(+) CD31(+) RTE T regs into CD45RA(-) CD31(+) memory T regs, wherein the lacking differentiation into CD45RA(-) CD31(-) memory T regs was partially replaced by the increased differentiation of ICOS(+) and ICOS(-) CD45RA(+) CD31(-) MN Tregs into CD45RA(-) CD31(-) memory T regs. In patients with HELLP syndrome, this alternatively increased differentiation of CD45RA(-) CD31(-) MN T regs seemed to be exaggerated, and presumably restored the suppressive activity of magnetically isolated ICOS(+) and ICOS(-) T regs, which were shown to be significantly less suppressive in pre-eclampsia patients, but not in HELLP syndrome patients. Hence, our findings propose that the regular differentiation of both ICOS(+) and ICOS(-) CD45RA(+) CD31(+) RTE T regs ensures a healthy pregnancy course, while their disturbed differentiation is associated with the occurrence of pre-eclampsia and HELLP syndrome. PMID- 26285100 TI - Photosynthesis of a combinatorial peptide library in the gas phase. AB - A strategy for generating large numbers of peptides from a relatively small number of precursors based on photosynthetic combination in the gas phase is presented. In this approach, electrospray ionization is used to create a combination of proton-bound dimers from a specified set of peptides present in solution. The dimers are then accumulated and isolated in an ion trap mass spectrometer. Photoexcitation (at 157 nm) leads to water elimination and the formation of larger peptide sequences that are characterized by subsequent isolation and collision-induced dissociation. The method is illustrated by using a set of four enkephalin-related and acetylated peptides to generate 12 larger peptide sequences. The ability to synthesize, isolate, and characterize many amino acid sequences from only a few precursors provides a fast and efficient means of characterizing properties of such species (e.g., dissociation patterns and reactivities). PMID- 26285101 TI - HIV/AIDS knowledge and stigma among women of reproductive age in Ethiopia. AB - HIV/AIDS stigma is one of the major public health challenges in Ethiopia. This study examined knowledge about HIV/AIDS and factors behind stigmatisation towards people living with the virus based on demographic and health survey data collected in 2011 from women in the age group 15-49 years. The result shows that 49.3% of rural women had adequate knowledge about HIV/AIDS compared with 74.7% of urban women. About three-fourths (72.1%) of the rural women had stigmatising attitudes towards PLWHA whilst the proportion in urban areas was only about a third (34.2%). The likelihood of having adequate knowledge about HIV/AIDS was significantly higher among educated women but lower among those living in Afar, Somali, and Gambella regions and Dire Dawa City. Women with higher levels of education and frequent access to media had a lower tendency to stigmatise people living with the virus. Adequate knowledge about HIV/AIDS was also significantly associated with lower likelihood of stigmatisation. The results generally indicate that HIV/AIDS stigma in Ethiopia is partly explained by people's knowledge about HIV/AIDS and by socio-cultural factors that shape their perception of the epidemic. Awareness-raising efforts should thus consider the socio-cultural contexts in which stigma occurs to tackle discrimination against people living with HIV/AIDS. PMID- 26285102 TI - B-cells in systemic sclerosis: emerging evidence from genetics to phenotypes. AB - PURPOSE OF REVIEW: This review aims to summarize current evidence for a role of B cells in the pathogenesis of systemic sclerosis (SSc) from genetics to phenotypes, with an emphasis on recent insights. RECENT FINDINGS: Multiple genomic analyses have associated several B-cell signalling genes with SSc. Moreover, interesting B-cell subset alterations and activation/memory marker changes have also been documented in SSc. Co-cultures of blood B-cells with dermal fibroblasts isolated from SSc patients demonstrated the induction of collagen, interleukin (IL)-6, transforming growth factor (TGF)-beta1, IL-1beta and chemokine (c-c motif) ligand 2 (CCL2) in the fibroblasts, following potential B-cell cues delivered to the fibroblasts. Plasma cell gene signatures were elevated in SSc patients' blood, and highly correlated with collagen gene expression. Finally, anti-CD20 B-cell depletion therapy not only improved skin disease but also preserved interstitial lung disease in early diffuse cutaneous disease. SUMMARY: Thus, there is resounding evidence that B-cells play a pivotal role in pathogenesis of SSc. However, the molecular pathways through which B cells may direct fibroblast function, SSc disease development and progression remain unclear, and warrant further study. PMID- 26285103 TI - Novel serology testing for sporadic inclusion body myositis: disease-specificity and diagnostic utility. AB - PURPOSE OF REVIEW: The purpose of this article is to discuss recent advances in serological testing for sporadic inclusion body myositis (sIBM) and to provide a review of their diagnostic utility and disease-specificity of auto-antibodies in sIBM. RECENT FINDINGS: The identification, prevalence and diagnostic utility of a new auto-antibody targeting cytosolic 5'-nucleotidase 1A (cN-1A) in the serum of sIBM patients have recently been published. These studies have shown that anti-cN 1A auto-antibodies have diagnostic utility for differentiating sIBM from other forms of myositis and from other neuromuscular diseases. Anti-cN-1A-positive patient sera are directed to multiple epitopes of cN-1A and contain, in addition to IgG, IgA and IgM, anti-cN-1A auto-antibodies. Recent studies have also shown a relatively high prevalence of these auto-antibodies in sera form Sjogren's syndrome and systemic lupus erythematosus patients. SUMMARY: The recent discovery of auto-antibodies to cN-1A provides a serological tool to aid the differentiation between inflammatory myopathies and supports the idea that apart from degeneration, an adaptive immune response may also play a role in sIBM pathophysiology. Future research will need to focus on standardization of methods to detect these auto-antibodies in order to further explore their specificity and diagnostic utility for sIBM. PMID- 26285104 TI - Hierarchical SrTiO3/NiFe2O4 composite nanostructures with excellent light response and magnetic performance synthesized toward enhanced photocatalytic activity. AB - Being capable of gathering advanced optical, electrical and magnetic properties originating from different components, multifunctional composite nanomaterials have been of concern increasingly. Herein, we have successfully demonstrated the preparation of SrTiO3/NiFe2O4 porous nanotubes (PNTs) and SrTiO3/NiFe2O4 particle in-tubes (PITs) via a single-spinneret electrospinning and a side-by-side spinneret electrospinning, respectively. The products were characterized by using scanning electron microscopy, transmission electron microscopy, X-ray diffraction, UV-visible diffuse reflectance spectra and a vibrating sample magnetometer in detail. The results indicate that SrTiO3/NiFe2O4 PNTs are the heterojunction nanotubes by connecting perovskite SrTiO3 and spinel NiFe2O4 nanoparticles, but SrTiO3/NiFe2O4 PITs are the self-assembled core/shell structures by embedding SrTiO3 nanoparticles into NiFe2O4 nanotubes. Compared with pure SrTiO3 nanofibers, the two SrTiO3/NiFe2O4 composites exhibit a powerful light response and excellent room temperature ferromagnetism. The magnetic separations directly reveal that such amazing recycling efficiencies of about 95% for SrTiO3/NiFe2O4 PNTs and about 99.5% for SrTiO3/NiFe2O4 PITs are obtained. Furthermore, both the magnetic composites perform considerable photocatalytic activity in the degradation of rhodamine B. We propose that Kirkendall-diffusion and phase-separation are probably responsible for the formation of SrTiO3/NiFe2O4 PITs, and this work could provide a feasible way to assemble the core/shell structures of different materials. PMID- 26285105 TI - Ultrafast excited state hydrogen atom transfer in salicylideneaniline driven by changes in aromaticity. AB - We investigated two important unresolved issues on excited state intramolecular proton transfer (ESIPT) reactions, i.e., their driving force and the charge state of the transferred species by means of quantum chemical topology. We related changes in the aromaticity of a molecule after electron excitation to reaction dynamics in an excited state. Additionally, we found that the conveyed particle has a charge intermediate between that of a bare proton and a neutral hydrogen atom. We anticipate that the analysis presented in this communication will yield valuable insights into ESIPT and other similar photochemical reactions. PMID- 26285106 TI - Post-Transplant Lymphoproliferative Disorder (PTLD) Manifesting in the Oral Cavity of a 13-Year-Old Liver Transplant Recipient (LTx). AB - BACKGROUND Post-transplant lymphoproliferative disorder (PTLD) is a potential complication of solid organ or bone marrow transplants. The main PTLD risk factors are: the Epstein-Barr virus (EBV), transplant type, and use of immunosuppressants. It mainly consists of an uncontrolled growth of lymphocytes in transplant recipients under chronic immunosuppressive therapy. About 85% of PTLDs are EBV-containing B-cell proliferations; 14% are T-cell proliferations, of which only 40% contain EBV; and the remaining 1% is NK-cell or plasmocyte proliferations. PTLD may present various clinical manifestations, from non specific mononucleosis-like syndrome to graft or other organ damage resulting from pathologic lymphocyte infiltration. PTLD may manifest in the oral cavity. CASE REPORT The objective of this study was to present the case of a 13-year-old female living-donor liver transplant recipient, resulting from biliary cirrhosis caused by congenital biliary atresia, with exophytic fibrous lesions on buccal mucosa and tongue. Exophytic and hyperplastic lesion of oral mucosa were removed and histopathological examination revealed polymorphic PTLD. The patient underwent 6 cycles of CHOP chemotherapy and all the oral lesions regressed completely. CONCLUSIONS All oral pathological lesions in organ transplant recipients need to be surgically removed and histopathologically examined because they present an increased risk of neoplastic transformations such as PTLD. PMID- 26285107 TI - Comparative Efficacy of Tongxinluo Capsule and Beta-Blockers in Treating Angina Pectoris: Meta-Analysis of Randomized Controlled Trials. AB - OBJECTIVE: There have been no systematic reviews, let alone meta-analyses, of randomized controlled trials (RCTs) comparing tongxinluo capsule (TXL) and beta blockers in treating angina pectoris. This study aimed to evaluate the efficacy of TXL and beta-blockers in treating angina pectoris by a meta-analysis of eligible RCTs. METHODS: The RCTs comparing TXL with beta-blockers (including metoprolol) in treating angina pectoris were searched and retrieved from databases including PubMed, Chinese National Knowledge Infrastructure, and WanFang Data. Eligible RCTs were selected according to prespecified criteria. Meta-analysis was performed on the odds ratios (OR) of symptomatic and electrocardiographic (ECG) improvements after treatment. Subgroup analysis, sensitivity analysis, meta-regression, and publication biases analysis were conducted to evaluate the robustness of the results. RESULTS: Seventy-three RCTs published between 2000 and 2014 with 7424 participants were eligible. Overall ORs comparing TXL with beta-blockers were 3.40 (95% confidence interval [CI], 2.97 3.89; p<0.0001) for symptomatic improvement and 2.63 (95% CI, 2.29-3.02; p<0.0001) for ECG improvement. Subgroup analysis and sensitivity analysis found no statistically significant dependence of overall ORs on specific study characteristics except efficacy criteria. Meta-regression found no significant except sample sizes for data on symptomatic improvement. Publication biases were statistically significant. CONCLUSION: TXL seems to be more effective than beta blockers in treating angina pectoris, on the basis of the eligible RCTs. Further RCTs are warranted to reduce publication bias and verify efficacy. PMID- 26285108 TI - 'I Used to Fight with Them but Now I Have Stopped!': Conflict and Doctor-Nurse Anaesthetists' Motivation in Maternal and Neonatal Care Provision in a Specialist Referral Hospital. AB - BACKGROUND AND OBJECTIVES: This paper analyses why and how conflicts occur and their influence on doctors and nurse-anaesthetists' motivation in the provision of maternal and neonatal health care in a specialist hospital. METHODOLOGY: The study used ethnographic methods including participant observation, conversation and in-depth interviews over eleven months in a specialist referral hospital in Ghana. Qualitative analysis software Nvivo 8 was used for coding and analysis of data. Main themes identified in the analysis form the basis for interpreting and reporting study findings. ETHICS STATEMENT: Ethical clearance was obtained from the Ghana Health Service Ethics Review board (approval number GHS-ERC:06/01/12) and from the University of Wageningen. Written consent was obtained from interview participants, while verbal consent was obtained for conversations. To protect the identity of the hospital and research participants pseudonyms are used in the article and the part of Ghana in which the study was conducted is not mentioned. RESULTS: Individual characteristics, interpersonal and organisational factors contributed to conflicts. Unequal power relations and distrust relations among doctors and nurse-anaesthetists affected how they responded to conflicts. Responses to conflicts including forcing, avoiding, accommodating and compromising contributed to persistent conflicts, which frustrated and demotivated doctors and nurse-anaesthetists. Demotivated workers exhibited poor attitudes in collaborating with co-workers in the provision of maternal and neonatal care, which sometimes led to poor health worker response to client care, consequently compromising the hospital's goal of providing quality health care to clients. CONCLUSION: To improve health care delivery in health facilities in Ghana, health managers and supervisors need to identify conflicts as an important phenomenon that should be addressed whenever they occur. Effective mechanisms including training managers and health workers on conflict management should be put in place. Additionally promoting communication and interaction among health workers can foster team spirit. Also resolving conflicts using the collaborating response may help to create a conducive work environment that will promote healthy work relations, which can facilitate the delivery of quality maternal and neonatal health care. However, such an approach requires that unequal power relations, which is a root cause of the conflicts is addressed. PMID- 26285109 TI - The Effects of Lithium Carbonate Supplemented with Nitrazepam on Sleep Disturbance during Cannabis Abstinence. AB - STUDY OBJECTIVE: Sleep disturbance is a hallmark feature of cannabis withdrawal. In this study we explored the effects of lithium treatment supplemented with nitrazepam on objective and subjective measures of sleep quality during inpatient cannabis withdrawal. METHODS: Treatment-seeking cannabis-dependent adults (n = 38) were admitted for 8 days to an inpatient withdrawal unit and randomized to either oral lithium (500 mg) or placebo, twice daily in a double-blind RCT. Restricted nitrazepam (10 mg) was available on demand (in response to poor sleep) on any 3 of the 7 nights. Dependent outcome measures for analysis included repeated daily objective actigraphy and subjective sleep measures throughout the 8 day detox, subjective cannabis withdrawal ratings, and detoxification completion rates. RESULTS: Based on actigraphy, lithium resulted in less fragmented sleep compared to placebo (p = 0.04), but no other objective measures were improved by lithium. Of the subjective measures, only nightmares were suppressed by lithium (p = 0.04). Lithium did not have a significant impact on the use of nitrazepam. Sleep bout length (p < 0.0001), sleep efficiency (p < 0.0001), and sleep fragmentation (p = 0.05) were improved on nights in which nitrazepam was used. In contrast, only night sweats improved with nitrazepam from the subjective measures (p = 0.04). A Cox regression with daily repeated measures of sleep efficiency averaged across all people in the study a predictor suggests that a one-unit increase in sleep efficiency (the ratio of total sleep time to the total time in bed expressed as a percentage) resulted in a 14.6% increase in retention in treatment (p = 0.008, Exp(B) = 0.854, 95% CI = 0.759-0.960). None of the other sleep measures, nor use of lithium or nitrazepam were significantly associated with retention in treatment. CONCLUSIONS: Lithium seems to have only limited efficacy on sleep disturbance in cannabis withdrawal. However the nitrazepam improved several actigraphy measures of sleep disturbance, warranting further investigation. Discord between objective and subjective sleep indices suggest caution in evaluating treatment interventions with self-report sleep data only. PMID- 26285110 TI - Performance of a Portable Sleep Monitoring Device in Individuals with High Versus Low Sleep Efficiency. AB - STUDY OBJECTIVES: Portable and automated sleep monitoring technology is becoming widely available to consumers, and one wireless system (WS) has recently surfaced as a research tool for sleep and sleep staging assessment outside the hospital/laboratory; however, previous research findings indicate low sensitivity for wakefulness detection. Because difficulty discriminating between wake and sleep is likely to affect staging performance, we sought to further evaluate the WS by comparing it to the gold-standard polysomnography (PSG) and actigraphy (ACT) for overall sleep/wakefulness detection and sleep staging, within high and low sleep efficiency sleepers. METHODS: Twenty-nine healthy adults (eight females) underwent concurrent WS, PSG, and ACT assessment in an overnight laboratory study. Epoch-by-epoch agreement was determined by comparing sleep/wakefulness decisions between the WS to both PSG and ACT, and for detection of light, deep, and rapid eye movement (REM) sleep stages between the WS and PSG. RESULTS: Sensitivity for wakefulness was low (40%), and an overestimation of total sleep time and underestimation of wake after sleep onset was observed. Prevalence and bias adjusted kappa statistic indicated moderate-to-high agreement between the WS and PSG for sleep staging. However, upon further inspection, WS performance varied by sleep efficiency, with the best performance during high sleep efficiency. CONCLUSIONS: The benefit of the WS as a sleep monitoring device over ACT is the ability to assess sleep stages, and our findings suggest this benefit is only realized within high sleep efficiency. Care should be taken to collect data under conditions where this is expected. PMID- 26285111 TI - The 2012 AASM Respiratory Event Criteria Increase the Incidence of Hypopneas in an Adult Sleep Center Population. AB - STUDY OBJECTIVES: To investigate the effect of the 2012 American Academy of Sleep Medicine (AASM) respiratory event criteria on severity and prevalence of obstructive sleep apnea (OSA) relative to previous respiratory event criteria. METHODS: A retrospective, randomized comparison was conducted in an Australian clinical sleep laboratory in a tertiary hospital. The polysomnograms (PSG) of 112 consecutive patients undertaking polysomnography (PSG) for suspected OSA were re scored for respiratory events using either 2007 AASM recommended (AASM2007Rec), 2007 AASM alternate (AASM2007Alt), Chicago criteria (AASM1999), or 2012 AASM recommended (AASM2012) respiratory event criteria. RESULTS: The median AHI using AASM2012 was approximately 90% greater than the AASM2007Rec AHI, approximately 25% greater than the AASM2007Alt AHI, and approximately 15% lower than the AASM1999 AHI. These changes increased OSA diagnoses by approximately 20% and 5% for AASM2007Rec and AASM2007Alt, respectively. Minimal changes in OSA diagnoses were observed between AASM1999 and AASM2012 criteria. To achieve the same OSA prevalence as AASM2012, the threshold for previous criteria would have to shift to 2.6/h, 3.6/h, and 7.3/h for AASM2007Rec, AASM2007Alt, and AASM1999, respectively. Differences between the AASM2007Rec and AASM2012 hypopnea indices (HI) were predominantly due to the change in desaturation levels required. Alterations to respiratory event duration rules had no effect on the HI. CONCLUSIONS: This study demonstrates that implementation of the 2012 AASM respiratory event criteria will increase the AHI in patients undergoing PSG, and more patients are likely to be diagnosed with OSA. COMMENTARY: A commentary on this article appears in this issue on page 1357. PMID- 26285112 TI - Sleep Related Scratching: A Distinct Parasomnia? AB - ABSTRACT: Pruritus (itching) during the sleep period can present as a symptom of dermatological or systemic disease, or as a parasomnia. Sleep related scratching as a primary parasomnia, exclusively confined to sleep in the absence of coexisting dermatological disorders, has not been well described. This case series describes three such patients, and discusses potentially relevant pathophysiology that can underlie itching or pain. Such cases of sleep related scratching may merit nosologic classification apart from previously defined parasomnias. PMID- 26285113 TI - Sleeping Pill Administration Time and Patient Subjective Satisfaction. AB - STUDY OBJECTIVES: Taking hypnotic agents 30 min before bedtime is the usual suggested administration time, but some patients report dissatisfaction with their sleeping pills. We investigated whether the timing of sleeping pill administration influences patient subjective satisfaction with these drugs. METHODS: One hundred twelve patients with primary insomnia currently taking benzodiazepine or nonbenzodiazepine gamma-aminobutyric acid (GABA) agonists as sleeping pills were selected. The time of administration for their sleeping pills, bedtime, sleep onset time, and wake up time were obtained from their medical records. Subjects were also categorized into satisfied or dissatisfied groups. RESULTS: Hypnotic agents administration time (p < 0.001) and bedtime (p < 0.001), but not sleep onset or wake up time, occurred later in the night in the satisfied group. The durations from administration of pills to sleep onset (33.6 +/- 20.7 min) and to wake up time (7.2 +/- 1.2 h) were significantly shorter in the satisfied group when compared to the dissatisfied group (135.9 +/- 73.4 min and 9.3 +/- 1.5 h for time to sleep onset and wake up, respectively). Logistic regression analysis revealed that patient subjective satisfaction with hypnotic agents could be predicted by a short duration from administration of pills to sleep onset (odds ratio = 0.01; 95% confidence interval [0.001-0.09]) and a short duration from administration of pills to wake up time (0.53; [0.31-0.89], F = 49.9, p < 0.001). CONCLUSIONS: Taking sleeping pills at a later time and a shorter interval between pill administration and wake up time may increase patient subjective satisfaction with hypnotic agents. We propose that physicians advise patients to take sleeping pills approximately 7 h before their usual getting-out-of-bed time instead of the current standard of 30 min before bedtime. PMID- 26285114 TI - Continuous and Loud Snoring Only in the Supine Posture. AB - Snoring and suspected sleep apneas are the most frequent causes for referral for a sleep study. Snoring varies across night and is usually recorded in all body postures. Here we report a unique patient showing continuous and loud snoring only in the supine posture. PMID- 26285116 TI - Bispectral Index in Evaluating Effects of Sedation Depth on Drug-Induced Sleep Endoscopy: DISE or No Dice. PMID- 26285115 TI - Psychosocial Characteristics of Children with Central Disorders of Hypersomnolence Versus Matched Healthy Children. AB - BACKGROUND: Hypersomnia of central origin from narcolepsy or idiopathic hypersomnia (IHS) is characterized by pathological levels of excessive daytime sleepiness (EDS). Central hypersomnia has historically been underdiagnosed and poorly understood, especially with respect to its impact on daytime functioning and quality of life in children. OBJECTIVE: Describe the psychosocial adjustment of children treated for narcolepsy or IHS on school performance, quality of life, and physical/extracurricular activities. METHODS: Using a matched case control design, we compared child self- and parent-reported data from thirty-three 8- to 16-year-olds with an established diagnosis of narcolepsy or IHS, according to ICSD-2 criteria, to that of 33 healthy children matched by age, race/ethnicity, gender, and household income. Assessments evaluated academic performance, quality of life and wellness, sleepiness, and participation in extracurricular activities. RESULTS: Compared to healthy controls, children with central hypersomnia had poorer daytime functioning in multiple domains. Children with hypersomnia missed more days of school and had lower grades than healthy controls. Children with hypersomnia had poorer quality of life by both parent and child report. Children with hypersomnia were significantly sleepier, had higher BMI, and were more likely to report a history of recent injury. Finally, children with hypersomnia engaged in fewer after-school activities than healthy controls. CONCLUSIONS: A range of significant psychosocial consequences are reported in children with hypersomnia even after a diagnosis has been made and treatments initiated. Health care professionals should be mindful of the psychosocial problems that may present in children with hypersomnia over the course of treatment. PMID- 26285117 TI - Physical Inactivity Is Associated with Moderate-Severe Obstructive Sleep Apnea. AB - STUDY OBJECTIVE: To investigate whether low levels of physical activity were associated with an increased occurrence of obstructive sleep apnea (OSA), OSA related symptoms, and cardiometabolic risk. METHODS: A case-control study design was used. OSA cases were patients referred to a sleep clinic for suspected OSA (n = 2,340). Controls comprised participants from the Busselton community (n = 1,931). Exercise and occupational activity were derived from questionnaire data. Associations were modelled using logistic and linear regression and adjusted for confounders. RESULTS: In comparison with moderate exercise, the high, low, and nil exercise groups had an odds ratio (OR) for moderate-severe OSA of 0.6 (95% CI 0.5-0.8), 1.6 (95% CI 1.2-2.0), and 2.7 (95% CI 1.9-3.7), respectively. Relative to men in heavy activity occupations, men in medium, light and sedentary occupations had an OR for moderate-severe OSA of 1.7 (95% CI 1.1-2.5), 2.1 (95% CI 1.4-3.2), and 1.8 (95% CI 1.2-2.8), respectively. Relative to women in medium activity occupations, women in light and sedentary occupations had an OR for moderate-severe OSA of 4.2 (95% CI 2.6-7.2) and 3.5 (2.0-6.0). OSA patients who adequately exercised had lower: levels of doctor-diagnosed depression (p = 0.047); symptoms of fatigue (p < 0.0001); systolic (p = 0.015) and diastolic blood pressure (p = 0.015); and C-reactive protein (CRP) (p = 0.003). CONCLUSIONS: Low levels of physical activity were associated with moderate-severe OSA. Exercise in individuals with OSA is associated with lower levels of depression, fatigue, blood pressure and CRP. PMID- 26285120 TI - Dietary Flavonoids as Xanthine Oxidase Inhibitors: Structure-Affinity and Structure-Activity Relationships. AB - The flavonoid family has been reported to possess a high potential for inhibition of xanthine oxidase (XO). This study concerned the structural aspects of inhibitory activities and binding affinities of flavonoids as XO inhibitors. The result indicated that the hydrophobic interaction was important in the binding of flavonoids to XO, and the XO inhibitory ability increased generally with increasing affinities within the class of flavones and flavonols. The planar structure and the C2?C3 double bonds of flavonoids were advantageous for binding to XO and for XO inhibition. Both the hydroxylation on ring B and the substitution at C3 were unfavorable for XO inhibition more profoundly than their XO affinity. The methylation greatly reduced the inhibition (0.75-3.07 times) but hardly affected the affinity. The bulky sugar substitutions of flavonoids decreased the inhibition (1.69-1.99 times) and lowered the affinities (4.20-9.22 times) to different degrees depending on the conjunction site. PMID- 26285119 TI - MicroRNA-200c Promotes Suppressive Potential of Myeloid-Derived Suppressor Cells by Modulating PTEN and FOG2 Expression. AB - Myeloid-derived suppressor cells (MDSCs) constitute one of the major populations that potently suppress anti-tumor immune responses and favor tumor growth in tumor microenvironment. However, the mechanism(s) regulating the differentiation and suppressive function of tumor-associated MDSCs remain(s) unclear. Here, we identified a microRNA-200c (miR-200c), whose expression was dramatically induced by tumor-derived factors. Meanwhile, we also demonstrated that GM-CSF was a main inducer of miR-200c in tumor environment, and miR-200c in turn promoted the expansion and immune suppressive activity of MDSCs via targeting phosphatase and tensin homolog (PTEN) and friend of Gata 2 (FOG2), which can lead to STAT3 and PI3K/Akt activation. Finally, we examined in vivo suppressive function of miR 200c transfected MDSCs and found that miR-200c could remarkably promote tumor growth via modifying MDSCs. Thus, GM-CSF induced miR-200c in tumor environment plays a critical role in governing the expansion and functions of tumor associated MDSCs and serves as a potential target in immunotherapy against tumor. PMID- 26285122 TI - A Newly-Identified Polymorphism in Rhesus Macaque Complement Factor H Modulates Binding Affinity for Meningococcal FHbp. AB - BACKGROUND: Two meningococcal serogroup B vaccines contain Factor H binding protein (FHbp). Binding of Factor H (FH) to FHbp was thought to be specific for human or chimpanzee FH. However, in a previous study an amino acid polymorphism in rhesus macaque FH domain 6, tyrosine at position 352 (Y352) was associated with high binding to FHbp, whereas histidine at position 352 (H352) was associated with low binding. METHODS AND RESULTS: Here we report that a second FH polymorphism at position 360 also affects macaque FH binding. Of 43 macaques, 11 had high FH binding and 32 had low binding. As in our previous study, all 11 animals with high binding had Y352, and 24 with low binding had H352. However the remaining eight with low FH binding had Y352, which was predicted to yield high binding. All eight had S360 instead of P360. Thus, three allelic variants at positions 352 and 360 affect macaque FH binding to FHbp: HP (low), YS (low), and YP (high). We measured binding affinity of each FH sequence type to FHbp by surface plasmon resonance. Two animals with high binding types (YS/YP and HP/YP) had dissociation constants (KD) of 10.4 and 18.2 nM, respectively, which were similar to human FH (19.8 nM). Two macaques with low binding (HP/HP and HP/YS) had KD values approximately five-fold higher (100.3 and 99.5 nM, respectively). A third macaque with low binding (YS/YS) had a KD value too high to be measured. CONCLUSIONS: Macaques have at least three allelic variants encoding FH with different affinities for FHbp (five genotypic combinations of these variants). Since in previous studies binding of FH to FHbp vaccines decreased protective antibody responses, our data will aid in selection of macaques with FH binding that is similar to humans for further investigation of FHbp vaccine immunogenicity. PMID- 26285121 TI - Nonconsensus Protein Binding to Repetitive DNA Sequence Elements Significantly Affects Eukaryotic Genomes. AB - Recent genome-wide experiments in different eukaryotic genomes provide an unprecedented view of transcription factor (TF) binding locations and of nucleosome occupancy. These experiments revealed that a large fraction of TF binding events occur in regions where only a small number of specific TF binding sites (TFBSs) have been detected. Furthermore, in vitro protein-DNA binding measurements performed for hundreds of TFs indicate that TFs are bound with wide range of affinities to different DNA sequences that lack known consensus motifs. These observations have thus challenged the classical picture of specific protein DNA binding and strongly suggest the existence of additional recognition mechanisms that affect protein-DNA binding preferences. We have previously demonstrated that repetitive DNA sequence elements characterized by certain symmetries statistically affect protein-DNA binding preferences. We call this binding mechanism nonconsensus protein-DNA binding in order to emphasize the point that specific consensus TFBSs do not contribute to this effect. In this paper, using the simple statistical mechanics model developed previously, we calculate the nonconsensus protein-DNA binding free energy for the entire C. elegans and D. melanogaster genomes. Using the available chromatin immunoprecipitation followed by sequencing (ChIP-seq) results on TF-DNA binding preferences for ~100 TFs, we show that DNA sequences characterized by low predicted free energy of nonconsensus binding have statistically higher experimental TF occupancy and lower nucleosome occupancy than sequences characterized by high free energy of nonconsensus binding. This is in agreement with our previous analysis performed for the yeast genome. We suggest therefore that nonconsensus protein-DNA binding assists the formation of nucleosome-free regions, as TFs outcompete nucleosomes at genomic locations with enhanced nonconsensus binding. In addition, here we perform a new, large-scale analysis using in vitro TF-DNA preferences obtained from the universal protein binding microarrays (PBM) for ~90 eukaryotic TFs belonging to 22 different DNA-binding domain types. As a result of this new analysis, we conclude that nonconsensus protein-DNA binding is a widespread phenomenon that significantly affects protein DNA binding preferences and need not require the presence of consensus (specific) TFBSs in order to achieve genome-wide TF-DNA binding specificity. PMID- 26285123 TI - Nanometer-Scale Pore Characteristics of Lacustrine Shale, Songliao Basin, NE China. AB - In shale, liquid hydrocarbons are accumulated mainly in nanometer-scale pores or fractures, so the pore types and PSDs (pore size distributions) play a major role in the shale oil occurrence (free or absorbed state), amount of oil, and flow features. The pore types and PSDs of marine shale have been well studied; however, research on lacustrine shale is rare, especially for shale in the oil generation window, although lacustrine shale is deposited widely around the world. To investigate the relationship between nanometer-scale pores and oil occurrence in the lacustrine shale, 10 lacustrine shale core samples from Songliao Basin, NE China were analyzed. Analyses of these samples included geochemical measurements, SEM (scanning electron microscope) observations, low pressure CO2 and N2 adsorption, and high-pressure mercury injection experiments. Analysis results indicate that: (1) Pore types in the lacustrine shale include inter-matrix pores, intergranular pores, organic matter pores, and dissolution pores, and these pores are dominated by mesopores and micropores; (2) There is no apparent correlation between pore volumes and clay content, however, a weak negative correlation is present between total pore volume and carbonate content; (3) Pores in lacustrine shale are well developed when the organic matter maturity (Ro) is >1.0% and the pore volume is positively correlated with the TOC (total organic carbon) content. The statistical results suggest that oil in lacustrine shale mainly occurs in pores with diameters larger than 40 nm. However, more research is needed to determine whether this minimum pore diameter for oil occurrence in lacustrine shale is widely applicable. PMID- 26285124 TI - Improvement on Automated Perimetry After Surgery for Idiopathic Intracranial Hypertension: Comment. PMID- 26285125 TI - Improvement on Automated Perimetry After Surgery for Idiopathic Intracranial Hypertension: Response. PMID- 26285126 TI - The Psychometric Properties of the Midlife Women's Symptom Index. AB - OBJECTIVE: To evaluate the psychometric properties of the Midlife Women's Symptom Index (MSI) among four racial/ethnic groups of midlife women in the United States. DESIGN: A secondary data analysis. SETTING: Internet communities/groups. PARTICIPANTS: A total of 494 midlife women with symptoms of menopause who self reported using an Internet survey and completed all sections of the MSI questionnaire. METHODS: Data were collected from January 1, 2008 to December 31, 2010. The psychometric properties of the MSI were evaluated using measures of internal consistency, item-total correlation coefficients, and discriminant validity. RESULTS: There were statistically significant differences in marital status, employment, income, religion, country of birth, level of education, diagnosed disease, and self-reported health status across the four racial/ethnic groups. The Kuder-Richardson Formula 20 (KR-20) coefficients for the three subscales of the MSI prevalence section (i.e., physical, psychological, and psychosomatic) ranged from 0.58 (psychosomatic symptoms in Whites) to 0.91 (psychological symptoms in Asian Americans). The Cronbach's alpha coefficients for the three subscale scores ranged from 0.60 (psychosomatic symptoms in Whites) to 0.93 (psychological symptoms in Asian Americans). The mean scores of the MSI differed significantly by race/ethnicity among midlife women of each menopausal status, except for the prevalence section of the psychosocial symptoms. CONCLUSION: The MSI has demonstrated an acceptable reliability and appropriate discriminant validity across the four racial/ethnic groups, except in the domain of psychosomatic symptoms. Health care providers as well as researchers could use the MSI to assess the symptoms of menopause of midlife women from diverse racial/ethnic backgrounds. PMID- 26285127 TI - Diurnal Variation of Hormonal and Lipid Biomarkers in a Molecular Epidemiology Like Setting. AB - INTRODUCTION: Many molecular epidemiology studies focusing on high prevalent diseases, such as metabolic disorders and cancer, investigate metabolic and hormonal markers. In general, sampling for these markers can occur at any time point during the day or after an overnight fast. However, environmental factors, such as light exposure and food intake might affect the levels of these markers, since they provide input for the internal time-keeping system. When diurnal variation is larger than the inter-individual variation, time of day should be taken into account. Importantly, heterogeneity in diurnal variation and disturbance of circadian rhythms among a study population might increasingly occur as a result of our increasing 24/7 economy and related variation in exposure to environmental factors (such as light and food). AIM: The aim of the present study was to determine whether a set of often used biomarkers shows diurnal variation in a setting resembling large molecular epidemiology studies, i.e., non-fasted and limited control possibilities for other environmental influences. RESULTS: We show that markers for which diurnal variation is not an issue are adrenocorticotropic hormone, follicle stimulating hormone, estradiol and high-density lipoprotein. For all other tested markers diurnal variation was observed in at least one gender (cholesterol, cortisol, dehydroepiandrosterone sulfate, free fatty acids, low-density lipoprotein, luteinizing hormone, prolactin, progesterone, testosterone, triglycerides, total triiodothyronine and thyroid-stimulating hormone) or could not reliably be detected (human growth hormone). DISCUSSION: Thus, studies investigating these markers should take diurnal variation into account, for which we provide some options. Furthermore, our study indicates the need for investigating diurnal variation (in literature or experimentally) before setting up studies measuring markers in routine and controlled settings, especially since time-of-day likely matters for many more markers than the ones investigated in the present study. PMID- 26285128 TI - Earliest modern human-like hand bone from a new >1.84-million-year-old site at Olduvai in Tanzania. AB - Modern humans are characterized by specialized hand morphology that is associated with advanced manipulative skills. Thus, there is important debate in paleoanthropology about the possible cause-effect relationship of this modern human-like (MHL) hand anatomy, its associated grips and the invention and use of stone tools by early hominins. Here we describe and analyse Olduvai Hominin (OH) 86, a manual proximal phalanx from the recently discovered >1.84-million-year-old (Ma) Philip Tobias Korongo (PTK) site at Olduvai Gorge (Tanzania). OH 86 represents the earliest MHL hand bone in the fossil record, of a size and shape that differs not only from all australopiths, but also from the phalangeal bones of the penecontemporaneous and geographically proximate OH 7 partial hand skeleton (part of the Homo habilis holotype). The discovery of OH 86 suggests that a hominin with a more MHL postcranium co-existed with Paranthropus boisei and Homo habilis at Olduvai during Bed I times. PMID- 26285129 TI - BDNF promoter methylation and genetic variation in late-life depression. AB - The regulation of the brain-derived neurotrophic factor (BDNF) is important for depression pathophysiology and epigenetic regulation of the BDNF gene may be involved. This study investigated whether BDNF methylation is a marker of depression. One thousand and twenty-four participants were recruited as part of a longitudinal study of psychiatric disorders in general population elderly (age ? 65). Clinical levels of depression were assessed using the Mini International Neuropsychiatric Interview for the diagnosis of major depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorder IV criteria, and the Centre for Epidemiologic Studies Depression Scale (CES-D) for assessment of moderate to severe depressive symptoms. Buccal DNA methylation at the two most widely studied BDNF promoters, I and IV, was investigated using the Sequenom MassARRAY platform that allows high-throughput investigation of methylation at individual CpG sites within defined genomic regions. In multivariate linear regression analyses adjusted for a range of participant characteristics including antidepressant use, depression at baseline, as well as chronic late-life depression over the 12-year follow-up, were associated with overall higher BDNF methylation levels, with two sites showing significant associations (promoter I, Delta mean = 0.4%, P = 0.0002; promoter IV, Delta mean = 5.4%, P = 0.021). Three single-nucleotide polymorphisms (rs6265, rs7103411 and rs908867) were also found to modify the association between depression and promoter I methylation. As one of the largest epigenetic studies of depression, and the first investigating BDNF methylation in buccal tissue, our findings highlight the potential for buccal BDNF methylation to be a biomarker of depression. PMID- 26285130 TI - The use of statins for the treatment of depression in patients with acute coronary syndrome. AB - This study aimed to investigate the effect of statins for the treatment of depression in individuals with acute coronary syndrome (ACS). We used 1-year follow-up data of a 24-week double-blind, placebo-controlled trial of escitalopram and a naturalistic prospective observational cohort study. Of 446 participants with comorbid depressive disorders and ACS at baseline, 300 participated in a randomised escitalopram trial and the remaining 146 participated in a naturalistic observational study. The participants in the two studies were approached for a 1-year follow-up investigation. Treatment response rates, defined as a ? 50% reduction in the Hamilton Depression Rating Scale (HAM D) and Beck Depression Inventory (BDI) scores, were used as the outcome variables. In the escitalopram trial, both HAM-D and BDI response rates were highest in patients taking escitalopram and statins together and lowest in patients receiving neither medication. Logistic regression analyses revealed that statin use was significantly associated with higher response rates on both the HAM-D and BDI at 1 year, whereas no such associations were found for escitalopram. In the naturalistic observational study, the response rates at 1 year did not differ significantly by statin use. Instead, the HAM-D response rate was significantly higher in patients taking lipophilic statins than in those who did not. In conclusion, statins may be effective for the treatment of depression independent of medical status and escitalopram use, and they may potentiate the antidepressant action of serotonergic antidepressants in patients with ACS. PMID- 26285131 TI - Elevated baseline serum glutamate as a pharmacometabolomic biomarker for acamprosate treatment outcome in alcohol-dependent subjects. AB - Acamprosate has been widely used since the Food and Drug Administration approved the medication for treatment of alcohol use disorders (AUDs) in 2004. Although the detailed molecular mechanism of acamprosate remains unclear, it has been largely known that acamprosate inhibits glutamate action in the brain. However, AUD is a complex and heterogeneous disorder. Thus, biomarkers are required to prescribe this medication to patients who will have the highest likelihood of responding positively. To identify pharmacometabolomic biomarkers of acamprosate response, we utilized serum samples from 120 alcohol-dependent subjects, including 71 responders (maintained continuous abstinence) and 49 non-responders (any alcohol use) during 12 weeks of acamprosate treatment. Notably, baseline serum glutamate levels were significantly higher in responders compared with non responders. Importantly, serum glutamate levels of responders are normalized after acamprosate treatment, whereas there was no significant glutamate change in non-responders. Subsequent functional studies in animal models revealed that, in the absence of alcohol, acamprosate activates glutamine synthetase, which synthesizes glutamine from glutamate and ammonia. These results suggest that acamprosate reduces serum glutamate levels for those who have elevated baseline serum glutamate levels among responders. Taken together, our findings demonstrate that elevated baseline serum glutamate levels are a potential biomarker associated with positive acamprosate response, which is an important step towards development of a personalized approach to treatment for AUD. PMID- 26285132 TI - Variation in the Williams syndrome GTF2I gene and anxiety proneness interactively affect prefrontal cortical response to aversive stimuli. AB - Characterizing the molecular mechanisms underlying the heritability of complex behavioral traits such as human anxiety remains a challenging endeavor for behavioral neuroscience. Copy-number variation (CNV) in the general transcription factor gene, GTF2I, located in the 7q11.23 chromosomal region that is hemideleted in Williams syndrome and duplicated in the 7q11.23 duplication syndrome (Dup7), is associated with gene-dose-dependent anxiety in mouse models and in both Williams syndrome and Dup7. Because of this recent preclinical and clinical identification of a genetic influence on anxiety, we examined whether sequence variation in GTF2I, specifically the single-nucleotide polymorphism rs2527367, interacts with trait and state anxiety to collectively impact neural response to anxiety-laden social stimuli. Two hundred and sixty healthy adults completed the Tridimensional Personality Questionnaire Harm Avoidance (HA) subscale, a trait measure of anxiety proneness, and underwent functional magnetic resonance imaging (fMRI) while matching aversive (fearful or angry) facial identity. We found an interaction between GTF2I allelic variations and HA that affects brain response: in individuals homozygous for the major allele, there was no correlation between HA and whole-brain response to aversive cues, whereas in heterozygotes and individuals homozygous for the minor allele, there was a positive correlation between HA sub-scores and a selective dorsolateral prefrontal cortex (DLPFC) responsivity during the processing of aversive stimuli. These results demonstrate that sequence variation in the GTF2I gene influences the relationship between trait anxiety and brain response to aversive social cues in healthy individuals, supporting a role for this neurogenetic mechanism in anxiety. PMID- 26285133 TI - Schizophrenia: a tale of two critical periods for prefrontal cortical development. AB - Schizophrenia is a disease of abnormal brain development. Considerable evidence now indicates that environmental factors have a causative role in schizophrenia. Elevated incidence of the disease has been linked to a wide range of disturbances in the prenatal environment and to social factors and drug intake during adolescence. Here we examine neurodevelopment of the prefrontal cortex in the first trimester of gestation and during adolescence to gain further insight into the neurodevelopmental processes that may be vulnerable in schizophrenia. Early embryonic development of the prefrontal cortex is characterized by cell proliferation, including renewal of progenitor cells, generation of early transient cell populations and neurogenesis of subcortical populations. Animal models show that curtailing early gestational cell proliferation produces schizophrenia-like pathology in the prefrontal cortex and mimics key behavioral and cognitive symptoms of the disease. At the other end of the spectrum, elimination of excitatory synapses is the fundamental process occurring during adolescent maturation in the prefrontal cortex. Adverse social situations that elevate stress increase dopamine stimulation of the mesocortical pathway and may lead to exaggerated synaptic pruning during adolescence. In a non-human primate model, dopamine hyperstimulation has been shown to decrease prefrontal pyramidal cell spine density and to be associated with profound cognitive dysfunction. Development of the prefrontal cortex in its earliest stage in gestation and in its final stage in adolescence represents two critical periods of vulnerability for schizophrenia in which cell proliferation and synaptic elimination, respectively, may be influenced by environmental factors. PMID- 26285134 TI - Differential Utilization of Dietary Fatty Acids in Benign and Malignant Cells of the Prostate. AB - Tumor cells adapt via metabolic reprogramming to meet elevated energy demands due to continuous proliferation, for example by switching to alternative energy sources. Nutrients such as glucose, fatty acids, ketone bodies and amino acids may be utilized as preferred substrates to fulfill increased energy requirements. In this study we investigated the metabolic characteristics of benign and cancer cells of the prostate with respect to their utilization of medium chain (MCTs) and long chain triglycerides (LCTs) under standard and glucose-starved culture conditions by assessing cell viability, glycolytic activity, mitochondrial respiration, the expression of genes encoding key metabolic enzymes as well as mitochondrial mass and mtDNA content. We report that BE prostate cells (RWPE-1) have a higher competence to utilize fatty acids as energy source than PCa cells (LNCaP, ABL, PC3) as shown not only by increased cell viability upon fatty acid supplementation but also by an increased beta-oxidation of fatty acids, although the base-line respiration was 2-fold higher in prostate cancer cells. Moreover, BE RWPE-1 cells were found to compensate for glucose starvation in the presence of fatty acids. Of notice, these findings were confirmed in vivo by showing that PCa tissue has a lower capacity in oxidizing fatty acids than benign prostate. Collectively, these metabolic differences between benign and prostate cancer cells and especially their differential utilization of fatty acids could be exploited to establish novel diagnostic and therapeutic strategies. PMID- 26285135 TI - Systematic Study on the Self-Assembled Hexagonal Au Voids, Nano-Clusters and Nanoparticles on GaN (0001). AB - Au nano-clusters and nanoparticles (NPs) have been widely utilized in various electronic, optoelectronic, and bio-medical applications due to their great potentials. The size, density and configuration of Au NPs play a vital role in the performance of these devices. In this paper, we present a systematic study on the self-assembled hexagonal Au voids, nano-clusters and NPs fabricated on GaN (0001) by the variation of annealing temperature and deposition amount. At relatively low annealing temperatures between 400 and 600 degrees C, the fabrication of hexagonal shaped Au voids and Au nano-clusters are observed and discussed based on the diffusion limited aggregation model. The size and density of voids and nano-clusters can systematically be controlled. The self-assembled Au NPs are fabricated at comparatively high temperatures from 650 to 800 degrees C based on the Volmer-Weber growth model and also the size and density can be tuned accordingly. The results are symmetrically analyzed and discussed in conjunction with the diffusion theory and thermodynamics by utilizing AFM and SEM images, EDS maps and spectra, FFT power spectra, cross-sectional line-profiles and size and density plots. PMID- 26285136 TI - High Inorganic Phosphate Intake Promotes Tumorigenesis at Early Stages in a Mouse Model of Lung Cancer. AB - Inorganic phosphate (Pi) is required by all living organisms for the development of organs such as bone, muscle, brain, and lungs, regulating the expression of several critical genes as well as signal transduction. However, little is known about the effects of prolonged dietary Pi consumption on lung cancer progression. This study investigated the effects of a high-phosphate diet (HPD) in a mouse model of adenocarcinoma. K-rasLA1 mice were fed a normal diet (0.3% Pi) or an HPD (1% Pi) for 1, 2, or 4 months. Mice were then sacrificed and subjected to inductively coupled plasma mass/optical emission spectrometry and laser ablation inductively coupled plasma mass-spectrometry analyses, western blot analysis, histopathological, immunohistochemical, and immunocytochemical analyses to evaluate tumor formation and progression (including cell proliferation, angiogenesis, and apoptosis), changes in ion levels and metabolism, autophagy, epithelial-to-mesenchymal transition, and protein translation in the lungs. An HPD accelerated tumorigenesis, as evidenced by increased adenoma and adenocarcinoma rates as well as tumor size. However, after 4 months of the HPD, cell proliferation was arrested, and marked increases in liver and lung ion levels and in energy production via the tricarboxylic acid cycle in the liver were observed, which were accompanied by increased autophagy and decreased angiogenesis and apoptosis. These results indicate that an HPD initially promotes but later inhibits lung cancer progression because of metabolic adaptation leading to tumor cell quiescence. Moreover, the results suggest that carefully regulated Pi consumption are effective in lung cancer prevention. PMID- 26285137 TI - The Efficacy of Synchronous Combination of Chemotherapy and EGFR TKIs for the First-Line Treatment of NSCLC: A Systematic Analysis. AB - BACKGROUND: The combination of chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) currently has become the hotspot issue in the treatment of non-small lung cancer (NSCLC). This systematic review was conducted to compare the efficacy and safety of the synchronous combination of these two treatments with EGFR TKIs or chemotherapy alone in advanced NSCLC. METHODS: EMBASE, PubMed, the Central Registry of Controlled Trials in the Cochrane Library (CENTRAL), Chinese biomedical literature database (CNKI) and meeting summaries were searched. The Phase II/III randomized controlled trials were selected by which patients with advanced NSCLC were randomized to receive a combination of EGFR TKIs and chemotherapy by synchronous mode vs. EGFR TKIs or chemotherapy alone. RESULTS: A total of six randomized controlled trials (RCTs) including 4675 patients were enrolled in the systematic review. The meta-analysis demonstrated that the synchronous combination group of chemotherapy and EGFR TKIs did not reach satisfactory results; there was no significant difference in overall survival (OS), time to progression (TTP) and objective response rate (ORR), compared with monotherapy (OS: HR = 1.05, 95%CI = 0.98-1.12; TTP: HR = 0.94, 95%CI = 0.89-1.00; ORR: RR = 1.07, 95%CI = 0.98-1.17), and no significant difference in OS and progression-free survival (PFS), compared with EGFR TKIs alone (OS: HR = 1.10, 95% CI = 0.83-1.46; PFS: HR = 0.86, 95% CI = 0.67-1.10). The patients who received synchronous combined therapy presented with increased incidences of grade 3/4 anemia (RR = 1.40, 95% CI = 1.10-1.79) and rash (RR = 7.43, 95% CI = 4.56-12.09), compared with chemotherapy, grade 3/4 anemia (RR = 6.71, 95% CI = 1.25-35.93) and fatigue (RR = 9.60, 95% CI = 2.28-40.86) compared with EGFR TKI monotherapy. CONCLUSIONS: The synchronous combination of chemotherapy and TKIs is not superior to chemotherapy or EGFR TKIs alone for the first-line treatment of NSCLC. PMID- 26285138 TI - Comparative Analysis of Transcriptional Profiles of Adult Schistosoma japonicum from Different Laboratory Animals and the Natural Host, Water Buffalo. AB - BACKGROUND: Schistosomiasis is one of the most widely distributed parasitic diseases in the world. Schistosoma japonicum, a zoonotic parasite with a wide range of mammalian hosts, is one of the major pathogens of this disease. Although numerous studies on schistosomiasis japonica have been performed using laboratory animal models, systematic comparative analysis of whole-genome expression profiles in parasites from different laboratory animals and nature mammalian hosts is lacking to date. METHODOLOGY/PRINCIPAL FINDINGS: Adult schistosomes were obtained from laboratory animals BALB/c mice, C57BL/6 mice, New Zealand white rabbits and the natural host, water buffaloes. The gene expression profiles of schistosomes from these animals were obtained and compared by genome-wide oligonucleotide microarray analysis. The results revealed that the gene expression profiles of schistosomes from different laboratory animals and buffaloes were highly consistent (r>0.98) genome-wide. Meanwhile, a total of 450 genes were identified to be differentially expressed in schistosomes which can be clustered into six groups. Pathway analysis revealed that these genes were mainly involved in multiple signal transduction pathways, amino acid, energy, nucleotide and lipid metabolism. We also identified a group of 1,540 abundantly and stably expressed gene products in adult worms, including a panel of 179 Schistosoma- or Platyhelminthes-specific genes that may be essential for parasitism and may be regarded as novel potential anti-parasite intervention targets for future research. CONCLUSIONS/SIGNIFICANCE: This study provides a comprehensive database of gene expression profiles of schistosomes derived from different laboratory animals and water buffaloes. An expanded number of genes potentially affecting the development of schistosomes in different animals were identified. These findings lay the foundation for schistosomiasis research in different laboratory animals and natural hosts at the transcriptional level and provide a valuable resource for screening anti-schistosomal intervention targets. PMID- 26285141 TI - Training for prescribing in-office and home phototherapy. AB - BACKGROUND/PURPOSE: One reason phototherapy use is lacking in the United States may be inadequate phototherapy education during dermatology training. The purpose of this study was to estimate the level of dermatology resident training with prescribing phototherapy and to see whether inadequate education may be contributing to the underuse of phototherapy in the United States. METHODS: A questionnaire was developed to assess resident education and comfort with prescribing phototherapy from the resident perspective. Botulinum toxin and radiation therapy training were used as positive and negative controls, respectively. Responses were tabulated and comparisons made using Fisher's exact test and Cochran-Armitage trend test. RESULTS: A total of 88 residents responded. 42% and 81% of respondents reported not receiving didactic education on prescribing in-office and home phototherapy, respectively, compared to 13% for botulinum toxin and 91% for radiation therapy. 29% and 76% reported not being comfortable prescribing in-office and home phototherapy, respectively, compared to 36% for botulinum toxin and 91% for radiation therapy. Phototherapy education satisfaction was positively correlated with comfort of prescribing, and comfort prescribing was positively correlated with actual prescribing of phototherapy. CONCLUSIONS: Training for prescribing phototherapy is lacking. Augmenting phototherapy training may help make home phototherapy more accessible for patients. PMID- 26285139 TI - Loss of the Homeodomain Transcription Factor Prep1 Perturbs Adult Hematopoiesis in the Bone Marrow. AB - Prep1, a TALE-family homeodomain transcription factor, has been demonstrated to play a critical role in embryonic hematopoiesis, as its insufficiency caused late embryonic lethality associated with defective hematopoiesis and angiogenesis. In the present study, we generated hematopoietic- and endothelial cell-specific Prep1-deficient mice and demonstrated that expression of Prep1 in the hematopoietic cell compartment is not essential for either embryonic or adult hematopoiesis, although its absence causes significant hematopoietic abnormalities in the adult bone marrow. Loss of Prep1 promotes cell cycling of hematopoietic stem/progenitor cells (HSPC), leading to the expansion of the HSPC pool. Prep1 deficiency also results in the accumulation of lineage-committed progenitors, increased monocyte/macrophage differentiation and arrested erythroid maturation. Maturation of T cells and B cells is also perturbed in Prep-deficient mice. These findings provide novel insight into the pleiotropic roles of Prep1 in adult hematopoiesis that were unrecognized in previous studies using germline Prep1 hypomorphic mice. PMID- 26285140 TI - Overactivation of the nuclear factor (erythroid-derived 2)-like 2-antioxidant response element pathway in hepatocytes decreases hepatic ischemia/reperfusion injury in mice. AB - Hepatic ischemia/reperfusion injury (IRI) is a critical component of hepatic surgery. Oxidative stress has long been implicated as a key player in IRI. In this study, we examine the cell-specific role of the nuclear factor (erythroid derived 2)-like 2 (Nrf2)-antioxidant response element pathway in warm hepatic IRI. Nrf2 knockout (KO) and wild-type (WT) animals and novel transgenic mice expressing a constitutively active nuclear factor (erythroid-derived 2)-like 2 (caNrf2) mutant in hepatocytes (AlbCre+/caNrf2+) and their littermate controls underwent partial hepatic ischemia or sham surgery. The animals were killed 6 hours after reperfusion, and their serum and tissue were collected for analysis. As compared to WT animals after ischemia/reperfusion (IR), Nrf2 KO mice had increased hepatocellular injury with increased serum alanine aminotransferase and aspartate aminotransferase, Suzuki score, apoptosis, an increased inflammatory infiltrate, and enhanced inflammatory cytokine expression. On the other hand, AlbCre+/caNrf2+ that underwent IR had significantly reduced serum transaminases, less necrosis on histology, and a less pronounced inflammatory infiltrate and inflammatory cytokine expression as compared to the littermate controls. However, there were no differences in apoptosis. Taken together, Nrf2 plays a critical role in our murine model of warm hepatic IRI, with Nrf2 deficiency exacerbating hepatic IRI and hepatocyte-specific Nrf2 overactivation providing protection against warm hepatic IRI. PMID- 26285142 TI - Diversity and antibiotic resistance profiles of Pseudomonads from a hospital wastewater treatment plant. AB - AIMS: To evaluate the diversity of Pseudomonads and antibiotic resistance profiles of Pseudomonas aeruginosa in a hospital wastewater treatment plant (HWTP) located in Rio de Janeiro city, Brazil. Due its intrinsic multidrug resistance and its ability to colonize several environments, we selected Ps. aeruginosa isolates as indicator of antimicrobial resistance frequency. METHODS AND RESULTS: Twenty-seven Ps. aeruginosa strains isolated from five stages of HWTP identified by rrs 16S rDNA sequencing were submitted against 12 antimicrobials through disc diffusion method. Among these isolates, 62.9% showed aztreonam resistance, followed by ticarcillin/clavulanic acid (33.3%) and cefepime (22.2%). Of these isolates, 22.2% were classified as multidrug-resistant (MDR >= 3 classes). Five 16S rRNA gene libraries of Pseudomonas genus were constructed, one for each stages of the plant, yielding 93 sequences clustered in 41 Operational Taxonomic Units (OTUs). Each treatment step showed unique OTU's composition, suggesting changes in Pseudomonas spp. communities during the process. Several Pseudomonas species involved in biodegradation and bioremediation of xenobiotics were detected suggesting a positive impact in the wastewater treatment. CONCLUSIONS: Our strategy using metagenomics associated with the isolation of Ps. aeruginosa strains as bio-indicator allowed us to assess their antimicrobial susceptibility, the viability and diversity of Pseudomonas species in the hospital wastewater. SIGNIFICANCE AND IMPACT OF THE STUDY: The presence of MDR bacteria from treated effluents alerts for the need to improve these systems to avoid the spreading of resistance genes in aquatic ecosystems. This has special relevance in Brazil, where a significant portion of the population has no access to treated water. PMID- 26285143 TI - Effect of Maximal Apnoea Easy-Going and Struggle Phases on Subarachnoid Width and Pial Artery Pulsation in Elite Breath-Hold Divers. AB - PURPOSE: The aim of the study was to assess changes in subarachnoid space width (sas-TQ), the marker of intracranial pressure (ICP), pial artery pulsation (cc TQ) and cardiac contribution to blood pressure (BP), cerebral blood flow velocity (CBFV) and cc-TQ oscillations throughout the maximal breath hold in elite apnoea divers. Non-invasive assessment of sas-TQ and cc-TQ became possible due to recently developed method based on infrared radiation, called near-infrared transillumination/backscattering sounding (NIR-T/BSS). METHODS: The experimental group consisted of seven breath-hold divers (six men). During testing, each participant performed a single maximal end-inspiratory breath hold. Apnoea consisted of the easy-going and struggle phases (characterised by involuntary breathing movements (IBMs)). Heart rate (HR) was determined using a standard ECG. BP was assessed using the photoplethysmography method. SaO2 was monitored continuously with pulse oximetry. A pneumatic chest belt was used to register thoracic and abdominal movements. Cerebral blood flow velocity (CBFV) was estimated by a 2-MHz transcranial Doppler ultrasonic probe. sas-TQ and cc-TQ were measured using NIR-T/BSS. Wavelet transform analysis was performed to assess cardiac contribution to BP, CBFV and cc-TQ oscillations. RESULTS: Mean BP and CBFV increased compared to baseline at the end of the easy phase and were further augmented by IBMs. cc-TQ increased compared to baseline at the end of the easy phase and remained stable during the IBMs. HR did not change significantly throughout the apnoea, although a trend toward a decrease during the easy phase and recovery during the IBMs was visible. Amplitudes of BP, CBFV and cc-TQ were augmented. sas-TQ and SaO2 decreased at the easy phase of apnoea and further decreased during the IBMs. CONCLUSIONS: Apnoea increases intracranial pressure and pial artery pulsation. Pial artery pulsation seems to be stabilised by the IBMs. Cardiac contribution to BP, CBFV and cc-TQ oscillations does not change throughout the apnoea. PMID- 26285144 TI - Quantitative theory for the longitudinal relaxation time of blood water. AB - PURPOSE: To propose and evaluate a model for the blood water T1 that takes into account the effects of hematocrit fraction, oxygenation fraction, erythrocyte hemoglobin concentration, methemoglobin fraction, and plasma albumin concentration. METHODS: Whole blood and lysed blood T1 data were acquired at magnetic fields of 3 Tesla (T), 7T, 9.4T, and 11.7T using inversion-recovery measurements and a home-built blood circulation system for maintaining physiological conditions. A quantitative model was derived based on multivariable fitting of this data. RESULTS: Fitting of the model to the data allowed determination of the different parameters describing the blood water T1 such as those for the diamagnetic and paramagnetic effects of albumin and hemoglobin, and the contribution of methemoglobin. The model correctly predicts blood T1 at multiple fields, as verified by comparison with existing literature. CONCLUSION: The model provides physical and physiological parameters describing the effects of hematocrit fraction, oxygenation, hemoglobin concentration, methemoglobin fraction, and albumin concentration on blood water T1 . It can be used to predict blood T1 at multiple fields. Magn Reson Med 76:270-281, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26285145 TI - HTLV-1 Tax Stimulates Ubiquitin E3 Ligase, Ring Finger Protein 8, to Assemble Lysine 63-Linked Polyubiquitin Chains for TAK1 and IKK Activation. AB - Human T lymphotropic virus type 1 (HTLV-1) trans-activator/oncoprotein, Tax, impacts a multitude of cellular processes, including I-kappaB kinase (IKK)/NF kappaB signaling, DNA damage repair, and mitosis. These activities of Tax have been implicated in the development of adult T-cell leukemia (ATL) in HTLV-1 infected individuals, but the underlying mechanisms remain obscure. IKK and its upstream kinase, TGFbeta-activated kinase 1 (TAK1), contain ubiquitin-binding subunits, NEMO and TAB2/3 respectively, which interact with K63-linked polyubiquitin (K63-pUb) chains. Recruitment to K63-pUb allows cross auto phosphorylation and activation of TAK1 to occur, followed by TAK1-catalyzed IKK phosphorylation and activation. Using cytosolic extracts of HeLa and Jurkat T cells supplemented with purified proteins we have identified ubiquitin E3 ligase, ring finger protein 8 (RNF8), and E2 conjugating enzymes, Ubc13:Uev1A and Ubc13:Uev2, to be the cellular factors utilized by Tax for TAK1 and IKK activation. In vitro, the combination of Tax and RNF8 greatly stimulated TAK1, IKK, IkappaBalpha and JNK phosphorylation. In vivo, RNF8 over-expression augmented while RNF8 ablation drastically reduced canonical NF-kappaB activation by Tax. Activation of the non-canonical NF-kappaB pathway by Tax, however, is unaffected by the loss of RNF8. Using purified components, we further demonstrated biochemically that Tax greatly stimulated RNF8 and Ubc13:Uev1A/Uev2 to assemble long K63-pUb chains. Finally, co-transfection of Tax with increasing amounts of RNF8 greatly induced K63-pUb assembly in a dose-dependent manner. Thus, Tax targets RNF8 and Ubc13:Uev1A/Uev2 to promote the assembly of K63-pUb chains, which signal the activation of TAK1 and multiple downstream kinases including IKK and JNK. Because of the roles RNF8 and K63-pUb chains play in DNA damage repair and cytokinesis, this mechanism may also explain the genomic instability of HTLV-1-transformed T cells and ATL cells. PMID- 26285146 TI - Polyphenolic profile and antioxidant effects of various parts of Artemisia annua L. AB - An annual Korean weed, Artemisia annua L., has been used as a folk medicine for the treatment of a number of diseases. Remarkably, among the 32 polyphenols characterized in various parts of plant tissue, including flowers, leafs, stems and roots, 10 compounds were detected for the first time using liquid chromatography-tandem mass spectrometry (LC/MS/MS). The quantification method was validated using structurally related external standards with determination coefficients (R(2) ) >=0.9995. The limits of detection and quantitation were 0.068-3.932 and 0.226-13.108 mg/L, respectively. The recoveries estimated at 50 and 100 mg/L ranged between 60.6-92.2 and 61.3-111%, respectively, with relative standard deviations <12%. The roots contained the largest concentration of identified components, while the flowers contained the least. The antioxidant capacity evaluated in terms of 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azinobis(3 ethylbenzothiazoline-6-sulfonic acid) radical cation-scavenging activities and reducing power was highest in the roots and lowest in the flowers. The findings are well correlated and suggest that the antioxidant capacities principally depend upon the polyphenol concentrations in each part of the plant. PMID- 26285147 TI - Isoflavonoids from Crotalaria albida Inhibit Adipocyte Differentiation and Lipid Accumulation in 3T3-L1 Cells via Suppression of PPAR-gamma Pathway. AB - Two 2"-isopropenyl dihydrofuran isoflavonoids (1 and 3), one 2"-isopropenyl dihydrofuran chromone (2), as well as 13 known compounds were isolated from the herbs of Crotalaria albida. Their structures and relative configurations were elucidated via NMR and HRESIMS analyses. The 2" S absolute configuration of 1 and 2 were deduced by comparing their NOESY spectra with that of 3, which was determined via single crystal X-ray diffraction (CuKalpha). The 3R absolute configuration of 1 was determined by CD. Compounds 1, 2, and 3 inhibit the adipocyte differentiation and lipid accumulation of 3T3-L1 through down regulation of PPAR-gamma activity. PMID- 26285148 TI - Dictionary Pair Learning on Grassmann Manifolds for Image Denoising. AB - Image denoising is a fundamental problem in computer vision and image processing that holds considerable practical importance for real-world applications. The traditional patch-based and sparse coding-driven image denoising methods convert 2D image patches into 1D vectors for further processing. Thus, these methods inevitably break down the inherent 2D geometric structure of natural images. To overcome this limitation pertaining to the previous image denoising methods, we propose a 2D image denoising model, namely, the dictionary pair learning (DPL) model, and we design a corresponding algorithm called the DPL on the Grassmann manifold (DPLG) algorithm. The DPLG algorithm first learns an initial dictionary pair (i.e., the left and right dictionaries) by employing a subspace partition technique on the Grassmann manifold, wherein the refined dictionary pair is obtained through a sub-dictionary pair merging. The DPLG obtains a sparse representation by encoding each image patch only with the selected sub-dictionary pair. The non-zero elements of the sparse representation are further smoothed by the graph Laplacian operator to remove the noise. Consequently, the DPLG algorithm not only preserves the inherent 2D geometric structure of natural images but also performs manifold smoothing in the 2D sparse coding space. We demonstrate that the DPLG algorithm also improves the structural SIMilarity values of the perceptual visual quality for denoised images using the experimental evaluations on the benchmark images and Berkeley segmentation data sets. Moreover, the DPLG also produces the competitive peak signal-to-noise ratio values from popular image denoising algorithms. PMID- 26285149 TI - Spartans: Single-Sample Periocular-Based Alignment-Robust Recognition Technique Applied to Non-Frontal Scenarios. AB - In this paper, we investigate a single-sample periocular-based alignment-robust face recognition technique that is pose-tolerant under unconstrained face matching scenarios. Our Spartans framework starts by utilizing one single sample per subject class, and generate new face images under a wide range of 3D rotations using the 3D generic elastic model which is both accurate and computationally economic. Then, we focus on the periocular region where the most stable and discriminant features on human faces are retained, and marginalize out the regions beyond the periocular region since they are more susceptible to expression variations and occlusions. A novel facial descriptor, high-dimensional Walsh local binary patterns, is uniformly sampled on facial images with robustness toward alignment. During the learning stage, subject-dependent advanced correlation filters are learned for pose-tolerant non-linear subspace modeling in kernel feature space followed by a coupled max-pooling mechanism which further improve the performance. Given any unconstrained unseen face image, the Spartans can produce a highly discriminative matching score, thus achieving high verification rate. We have evaluated our method on the challenging Labeled Faces in the Wild database and solidly outperformed the state-of-the-art algorithms under four evaluation protocols with a high accuracy of 89.69%, a top score among image-restricted and unsupervised protocols. The advancement of Spartans is also proven in the Face Recognition Grand Challenge and Multi-PIE databases. In addition, our learning method based on advanced correlation filters is much more effective, in terms of learning subject-dependent pose-tolerant subspaces, compared with many well-established subspace methods in both linear and non-linear cases. PMID- 26285150 TI - A General-Thresholding Solution for lp (0 < p <1) Regularized CT Reconstruction. AB - It is well known that l1 minimization can be used to recover sufficiently sparse unknown signals in the compressive sensing field. The lp regularization method, a generalized version between the well-known l1 regularization and the l0 regularization, has been proposed for a sparser solution. In this paper, we derive several quasi-analytic thresholding representations for the lp(0 < p < 1) regularization. The derived representations are exact matches for the well-known soft-threshold filtering for the l1 regularization and the hard-threshold filtering for the l0 regularization. The error bounds of the approximate general formulas are analyzed. The general-threshold representation formulas are incorporated into an iterative thresholding framework for a fast solution of an lp regularized computed tomography (CT) reconstruction. A series of simulated and realistic data experiments are conducted to evaluate the performance of the proposed general-threshold filtering algorithm for CT reconstruction, and it is also compared with the well-known re-weighted approach. Compared with the re weighted algorithm, the proposed general-threshold filtering algorithm can substantially reduce the necessary view number for an accurate reconstruction of the Shepp-Logan phantom. In addition, the proposed general-threshold filtering algorithm performs well in terms of image quality, reconstruction accuracy, convergence speed, and sensitivity to parameters. PMID- 26285151 TI - Nonlinear Hyperspectral Unmixing With Robust Nonnegative Matrix Factorization. AB - We introduce a robust mixing model to describe hyperspectral data resulting from the mixture of several pure spectral signatures. The new model extends the commonly used linear mixing model by introducing an additional term accounting for possible nonlinear effects, that are treated as sparsely distributed additive outliers. With the standard nonnegativity and sum-to-one constraints inherent to spectral unmixing, our model leads to a new form of robust nonnegative matrix factorization with a group-sparse outlier term. The factorization is posed as an optimization problem, which is addressed with a block-coordinate descent algorithm involving majorization-minimization updates. Simulation results obtained on synthetic and real data show that the proposed strategy competes with the state-of-the-art linear and nonlinear unmixing methods. PMID- 26285152 TI - High-Resolution Light Field Capture With Coded Aperture. AB - Acquiring light field with larger angular resolution and higher spatial resolution in low cost is the goal of light field capture. Combining or modifying traditional optical cameras is a usual method for designing light field capture equipment, among which most models should deliberate trade-off between angular and spatial resolution, but augmenting coded aperture avoids this consideration by multiplexing information from different views. On the basis of coded aperture, this paper suggests an improved light field camera model that has double measurements and one mask. The two compressive measurements are respectively realized by a coded aperture and a random convolution CMOS imager, the latter is used as imaging sensor of the camera. The single mask design permits high light efficiency, which enables the sampling images to have high clarity. The double measurement design keeps more correlation information, which is conductive to enhancing the reconstructed light field. The higher clarity and more correlation of samplings mean higher quality of rebuilt light field, which also means higher resolution under condition of a lower PSNR requirement for rebuilt light field. Experimental results have verified advantage of the proposed design: compared with the representative mask-based light field camera models, the proposed model has the highest reconstruction quality and a higher light efficiency. PMID- 26285153 TI - Gradient Domain Guided Image Filtering. AB - Guided image filter (GIF) is a well-known local filter for its edge-preserving property and low computational complexity. Unfortunately, the GIF may suffer from halo artifacts, because the local linear model used in the GIF cannot represent the image well near some edges. In this paper, a gradient domain GIF is proposed by incorporating an explicit first-order edge-aware constraint. The edge-aware constraint makes edges be preserved better. To illustrate the efficiency of the proposed filter, the proposed gradient domain GIF is applied for single-image detail enhancement, tone mapping of high dynamic range images and image saliency detection. Both theoretical analysis and experimental results prove that the proposed gradient domain GIF can produce better resultant images, especially near the edges, where halos appear in the original GIF. PMID- 26285155 TI - Copper(II)-Specific Fluorogenic Task-Specific Ionic Liquids as Selective Fluorescence Probes and Recyclable Extractants. AB - The designed synthesis of a series of copper(II) specific fluorogenic hydrophobic task-specific ionic liquids (TSILs) from a new naphthalene-based tetradentate ligand is reported. Absorption and fluorescence spectral studies reveal both the ligand and its derivative TSILs show exclusive selectivity towards copper(II) ions. The Stern-Volmer method for calculation of the detection limit for ligand and TSIL1-3 shows values of 0.12, 20, 17, and 15 MUM, respectively. Extraction and striping studies by doping these TSILs in [bmim][NTf2] demonstrated that these TSILs are recyclable extractants for the selective recovery of Cu(II) ions from a mixture of 14 relevant metal chloride aqueous solutions in biphasic liquid liquid extraction with approximately 95% recovery. PMID- 26285154 TI - Ablation of Doublecortin-Like Kinase 1 in the Colonic Epithelium Exacerbates Dextran Sulfate Sodium-Induced Colitis. AB - Doublecortin-like kinase 1 (Dclk1), a microtubule-associated kinase, marks the fifth lineage of intestinal epithelial cells called tuft cells that function as tumor stem cells in Apc mutant models of colon cancer. In order to determine the role of Dclk1 in dextran sulfate sodium (DSS) induced colonic inflammation both intestinal epithelial specific Dclk1 deficient (VillinCre;Dclk1f/f) and control (Dclk1f/f) mice were fed 3% DSS in drinking water for 9 days, allowed to recover for 2 days, and killed. The clinical and histological features of DSS-induced colitis were scored and immunohistochemical, gene expression, pro-inflammatory cytokines/chemokines, and immunoblotting analyses were used to examine epithelial barrier integrity, inflammation, and stem and tuft cell features. In DSS-induced colitis, VillinCre;Dclk1f/f mice demonstrated exacerbated injury including higher clinical colitis scores, increased epithelial barrier permeability, higher levels of pro-inflammatory cytokines and chemokines, decreased levels of Lgr5, and dysregulated Wnt/b-Catenin pathway genes. These results suggest that Dclk1 plays an important role in regulating colonic inflammatory response and colonic epithelial integrity. PMID- 26285156 TI - REST rs3796529 variant does not confer susceptibility to Alzheimer's disease. PMID- 26285157 TI - Inter-device comparison of retinal sensitivity measurements: the CenterVue MAIA and the Nidek MP-1. AB - BACKGROUND: Our aim is to compare retinal sensitivity measurements obtained on two microperimeters: the CenterVue MAIA and the Nidek MP-1. DESIGN: A prospective study was conducted in a private ophthalmology clinic. PARTICIPANTS: Seventeen individuals with a range of stable macular function were recruited as participants. METHODS: Microperimetry in one eye with identical test strategy in both devices, with randomized testing order, is used. MAIN OUTCOME MEASURES: The main outcome measures include differences in mean sensitivity (MS), point-wise sensitivity (PWS) and duration. Limits of agreement (LoA) in MS and pooled PWS were calculated. Concordance in scotoma assessment was analysed by kappa (kappa) agreement of local defect classification (LDC), LoA in number of scotomatous loci detected and congruence in scotoma localization (CSL). RESULTS: Median (interquartile range) MS of the MP-1 and MAIA was 13.3 (5.6-18.1) and 21.2 (14.5 27.0) dB, (P < 0.05). Mean difference in PWS was 7.3 dB (MAIA > MP-1). Median (interquartile range) duration for the MP-1 and MAIA was 10'28" (7'17"-11'53") and 8'46" (8'30"-9'06"), (P = 0.21). LoA for MS and pooled PWS was 1.4 to 13.3 dB and -3.9 to 18.5 dB. There was moderate agreement between the devices for LDC (weighted kappa = 0.55, P < 0.05). LoA in number of scotomatous loci detected was -13 to 18. CSL varied from 0 to 100% and correlated strongly with increasing scotoma size. CONCLUSIONS: The large LoA and variation in scotoma mapping concordance suggest that the same microperimeter should be used for follow-up examination. We recommend caution in comparing results derived from different types of microperimeters. PMID- 26285158 TI - Sebox regulates mesoderm formation in early amphibian embryos. AB - BACKGROUND: Mix/Bix genes are important regulators of mesendoderm formation during vertebrate embryogenesis. Sebox, an additional member of this gene family, has been implicated in endoderm formation during early embryogenesis in zebrafish. However, it remains unclear whether Sebox plays a unique role in early Xenopus embryos. RESULTS: In this study, we provide evidence that Sebox is uniquely required for the formation of mesoderm during early Xenopus embryogenesis. Sebox is dynamically expressed in the involuted mesoderm during gastrulation. It is activated by Nodal/Activin signaling and modulated by zygotic Wnt/beta-catenin signaling. Overexpression of Sebox perturbs movements during convergent extension and inhibits the expression of mesodermal, but not endodermal, genes induced by Nodal/Activin signaling. Depletion of Sebox using a specific morpholino increases the expression of noncanonical wnt5a, wnt5b, and wnt11b. Depletion of Sebox also up-regulates the expression of pcdh8.2, a paraxial mesoderm-specific protocadherin, in a Wnt11B-dependent manner. Sebox morphants display reduced development of the head and notochord. CONCLUSIONS: Our findings illustrate that Sebox, a unique member of the Mix/Bix gene family, functions downstream of Nodal/Activin signaling and is required for the proper expression of noncanonical Wnt ligands and the normal development of mesoderm in Xenopus. PMID- 26285159 TI - Concomitant high expression of BRAFV600E, P-cadherin and cadherin 6 is associated with High TNM stage and lymph node metastasis in conventional papillary thyroid carcinoma. AB - CONTEXT AND OBJECTIVE: BRAFV600E mutation is the most common activating mutation associated with aggressive behaviours in human tumours including conventional papillary thyroid carcinoma (cPTC). P-cadherin and cadherin 6 have been shown to be mesenchymal-associated cadherins and promote cancer cell invasion and metastasis. The purpose of this study was to examine BRAFV600E, P-cadherin and cadherin 6 expressions in cPTC and to assess the association of their expression with clinicopathological indicators. METHODS: BRAFV600E, P-cadherin and cadherin 6 protein expressions in 80 cPTCs, 61 nodular hyperplasia and 76 normal thyroid tissues were examined by immunohistochemistry. The correlation of their protein expression with clinicopathological indicators of cPTC was statistically analysed. RESULTS: Protein expression of BRAFV600E, P-cadherin and cadherin 6 was upregulated in cPTC. High protein expression of BRAFV600E, P-cadherin and cadherin 6 was significantly correlated with high TNM stage and lymph node metastasis (LNM) (P < 0.001). Furthermore, BRAFV600E, P-cadherin and cadherin 6 protein expressions were correlated with one another. BRAFV600E high expression combined with both P-cadherin and cadherin-6 high expressions had stronger correlation with high TNM stage and LNM when compared with BRAFV600E high expression combined with either P-cadherin or cadherin-6 high expression (P = 0.042, 0.017 for TNM stage and P = 0.003, 0.006 for LNM, respectively) and only BRAFV600E high expression (P < 0.001 for both TNM stage and LNM). CONCLUSIONS: Concomitant high expression of BRAFV600E, P-cadherin and cadherin 6 is strongly associated with high TNM stage and LNM in cPTC. PMID- 26285160 TI - Organochlorine insecticides DDT and chlordane in relation to survival following breast cancer. AB - Organochlorine insecticides have been studied extensively in relation to breast cancer incidence, and results from two meta-analyses have been null for late-life residues, possibly due to measurement error. Whether these compounds influence survival remains to be fully explored. We examined associations between organochlorine insecticides [p,p'-DDT (dichlorodiphenyltrichloroethane), its primary metabolite, p,p'-DDE, and chlordane] assessed shortly after diagnosis and survival among women with breast cancer. A population-based sample of women diagnosed with a first primary invasive or in situ breast cancer in 1996-1997 and with available organochlorine blood measures (n = 633) were followed for vital status through 2011. After follow-up of 5 and 15 years, we identified 55 and 189 deaths, of which 36 and 74, respectively, were breast cancer-related. Using Cox regression models, we estimated the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for lipid-adjusted organochlorine concentrations with all-cause and breast cancer-specific mortality. At 5 years after diagnosis, the highest tertile of DDT concentration was associated with all cause (HR = 2.19; 95% CI: 1.02, 4.67) and breast cancer-specific (HR = 2.72; 95% CI: 1.04, 7.13) mortality. At 15 years, middle tertile concentrations of DDT (HR = 1.42; 95% CI 0.99, 2.06) and chlordane (HR = 1.42; 95% CI: 0.94, 2.12) were modestly associated with all-cause and breast cancer-specific mortality. Third tertile DDE concentrations were inversely associated with 15-year all-cause mortality (HR = 0.66; 95% CI: 0.44, 0.99). This is the first population-based study in the United States to show that DDT may adversely impact survival following breast cancer diagnosis. Further studies are warranted given the high breast cancer burden and the ubiquity of these chemicals. PMID- 26285161 TI - Eight-year results of the Spiesser study, a randomized trial comparing de novo sirolimus and cyclosporine in renal transplantation. AB - We present the results at 8 years of the Spiesser study, a randomized trial comparing de novo sirolimus and cyclosporine in kidney transplant recipients at low immunologic risk. We assessed estimated glomerular filtration (eGFR), graft, patient, and death-censored graft survival (log-rank compared), de novo DSA appearance, risk of malignancy, post-transplant diabetes mellitus (PTDM), and anemia. Intent-to-treat and on-treatment analyses were performed. Graft survival was similar in both groups (sirolimus: 73.3%, cyclosporine: 77.7, P = 0.574). No difference was observed between treatment groups concerning patient survival (P = 0.508) and death-censored graft survival (P = 0.858). In conditional intent-to treat analysis, mean eGFR was greater in sirolimus than in cyclosporine group (62.5 +/- 27.3 ml/min vs. 47.8 +/- 17.1 ml/min, P = 0.004), in particular because graft function was excellent in patients maintained under sirolimus (eGFR = 74.0 ml/min). Importantly, no detrimental impact was observed in patients in whom sirolimus has been withdrawn (eGFR = 49.5 ml/min). Overall, 17 patients showed de novo DSAs, with no difference between the two groups (P = 0.520). Malignancy did not differ by treatment. An initial maintenance regimen based on sirolimus provides a long-term improvement in renal function for kidney transplant patients, especially for those maintained on sirolimus. PMID- 26285162 TI - False normal Lung Clearance Index in infants with cystic fibrosis due to software algorithms. AB - BACKGROUND: Lung clearance index (LCI), a marker of ventilation inhomogeneity, is elevated early in children with cystic fibrosis (CF). However, in infants with CF, LCI values are found to be normal, although structural lung abnormalities are often detectable. We hypothesized that this discrepancy is due to inadequate algorithms of the available software package. AIM: Our aim was to challenge the validity of these software algorithms. METHODS: We compared multiple breath washout (MBW) results of current software algorithms (automatic modus) to refined algorithms (manual modus) in 17 asymptomatic infants with CF, and 24 matched healthy term-born infants. The main difference between these two analysis methods lies in the calculation of the molar mass differences that the system uses to define the completion of the measurement. RESULTS: In infants with CF the refined manual modus revealed clearly elevated LCI above 9 in 8 out of 35 measurements (23%), all showing LCI values below 8.3 using the automatic modus (paired t-test comparing the means, P < 0.001). Healthy infants showed normal LCI values using both analysis methods (n = 47, paired t-test, P = 0.79). The most relevant reason for false normal LCI values in infants with CF using the automatic modus was the incorrect recognition of the end-of-test too early during the washout. CONCLUSION: We recommend the use of the manual modus for the analysis of MBW outcomes in infants in order to obtain more accurate results. This will allow appropriate use of infant lung function results for clinical and scientific purposes. PMID- 26285163 TI - The impact of ranibizumab on the level of intercellular adhesion molecule type 1 in the vitreous of eyes with proliferative diabetic retinopathy. AB - PURPOSE: This study was to investigate the impact of ranibizumab on the level of intercellular adhesion molecule type 1 (ICAM-1) in the vitreous of eyes with PDR. METHODS: This is an interventional case-control study. A total of 82 eyes from 82 patients who had undergone vitreous surgery for the treatment of retinal disorders were included. Twenty-two eyes with PDR received an intravitreal ranibizumab injection (IVR) 3-7 days before vitrectomy and were grouped as 'PDR with recent IVR' or Group 1. Sixteen eyes with PDR received IVR more than 7 days before vitrectomy and were grouped as 'PDR with remote IVR' or Group 2. Twenty two matched PDR eyes did not receive IVR before vitrectomy and were grouped as 'PDR without IVR' or Group 3. Finally, 22 eyes from 22 patients with idiopathic macular pucker (IMP) served as the 'non-diabetic control' group, or Group 4. Vitreous samples were obtained at the time of vitrectomy from all eyes, and the levels of vascular endothelium growth factor (VEGF) and ICAM-1 were analysed using ELISA. RESULTS: PDR without IVR (Group 3) had the highest vitreous VEGF concentration; the difference was significant compared with those in the PDR with recent IVR (Group 1), PDR with remote IVR (Group 2) and the non-diabetic control group (Group 4) (p < 0.001). Group 2 had a lower vitreous VEGF level than Group 1 (p = 0.041). Group 1 had the highest vitreous ICAM-1 levels (p < 0.001 versus. Groups 2, 3 and 4); Group 2 had a lower vitreous ICAM-1 level than Group 3 (p = 0.028). CONCLUSION: The vitreous fluid level of ICAM-1 was significantly increased within 1 week of IVR administration, but markedly decreased after a week of administration in eyes with PDR. This suggests that leucostasis, vascular leakage and endothelial dysfunction may be amplified in the early days after IVR, but that a therapeutic effect of IVR in these processes may appear after 1 week of ranibizumab administration in eyes with PDR. PMID- 26285164 TI - Jacobsen syndrome: Advances in our knowledge of phenotype and genotype. AB - In 1973, the Danish geneticist Petrea Jacobsen described a three-generation family in which the proband carried a presumed terminal deletion at the end of the long arm of chromosome 11 (11q). This patient had dysmorphic features, congenital heart disease, and intellectual disability. Since Dr. Jacobsen's initial report, over 200 patients with Jacobsen syndrome have been reported, suggesting that Jacobsen syndrome is a contiguous gene disorder. With the advent of high resolution deletion mapping and the completion of the human genome sequencing project, a comprehensive genotype/phenotype analysis for Jacobsen syndrome became possible. In this article, we review research describing individual causal genes in distal 11q that contribute to the overall Jacobsen syndrome clinical phenotype. Through a combination of human genetics and the use of genetically engineered animal models, causal genes have been identified for the clinical problems in JS that historically have caused the greatest morbidity and mortality: congenital heart disease, the Paris-Trousseau bleeding disorder, intellectual disability, autism, and immunodeficiency. Insights gained from these studies are being applied for future drug development and clinical trials, as well as for a potential strategy for the prevention of certain forms of congenital heart disease. The results of these studies will likely not only improve the prognostic and therapeutic approaches for patients with Jacobsen syndrome, but also for the general population afflicted with these problems. PMID- 26285165 TI - Protease activated receptor-1 antagonist ameliorates the clinical symptoms of experimental autoimmune encephalomyelitis via inhibiting breakdown of blood-brain barrier. AB - To evaluate the question of whether protease activated receptor-1 (PAR-1) antagonist is a potential therapeutic target in multiple sclerosis, we treated experimental autoimmune encephalomyelitis (EAE) mice with two PAR-1 antagonists, KC-A0590 and SCH-530348. Treatment with both antagonists resulted in a significant decrease in the clinical characteristics of EAE mice by suppressing demyelination and infiltration of inflammatory cells in the spinal cord and brain, as well as a significantly reducing the increased thrombin and tumor necrosis factor-alpha. Profound leakage of dextran was observed in the brain of EAE mice. However, treatment with PAR-1 antagonists resulted in the stabilization of vascular endothelial cells and reduced blood-brain barrier breakdown with suppression of inflammatory response. Treatment with PAR-1 antagonists also resulted in down-regulated expression of matrix metalloproteinase-9 and preserved expression of occludin and zonula occludens (ZO)-1 in the brain and their significant expression was confirmed in neurons, astrocytes, and vascular endothelial cells. Finally, endothelial cells and primary cultured astrocytes were treated with PAR-1 antagonists; both antagonists suppressed thrombin-induced breakdown of ZO-1 in endothelial cells and secretion of matrix metalloproteinase 9 in astrocytes. Collectively, our results suggest that PAR-1 antagonist is effective in attenuation of the clinical symptoms of EAE mice by stabilizing the blood-brain barrier and may have therapeutic potential for treatment of multiple sclerosis. PMID- 26285166 TI - Kinetic Profiling of Catalytic Organic Reactions as a Mechanistic Tool. AB - The use of modern kinetic tools to obtain virtually continuous reaction progress data over the course of a catalytic reaction opens up a vista that provides mechanistic insights into both simple and complex catalytic networks. Reaction profiles offer a rate/concentration scan that tells the story of a batch reaction time course in a qualitative "fingerprinting" manner as well as in quantitative detail. Reaction progress experiments may be mathematically designed to elucidate catalytic rate laws from only a fraction of the number of experiments required in classical kinetic measurements. The information gained from kinetic profiles provides clues to direct further mechanistic analysis by other approaches. Examples from a variety of catalytic reactions spanning two decades of the author's work help to delineate nuances on a central mechanistic theme. PMID- 26285167 TI - Quantitation of baby wipes lotion transfer to premature and neonatal skin. AB - Exposure to topically applied substances occurs routinely in premature and hospitalized infant care. Safety determinations are most accurate when exposures are based on appropriately designed studies to capture variations in practice patterns and population heterogeneity. Current safety assessments may not reflect actual practice resulting in overly conservative or understated default assumptions for toxicological determinations. We quantified the amount of baby wipes lotion transferred to premature and term neonatal skin as grams/kg body weight/day. We observed the soil type and number of wipes used for skin cleansing and measured lotion transfer from one wipe applied to freshly clean, dry skin. A Bayesian imputation approach was applied to compute lotion exposure and produce summary statistics. Model covariates were age and weight at evaluation, gender, soil type, soil amount, and number of diaper changes per day. Lotion transfer was measured for 66 premature and 55 term neonates with 449 and 254 evaluations, respectively. The wipes per day was 12.52 overall (all infants and soils), 12.78 for premature and 12.21 for term neonates. Lotion transfer was 0.20 g/kg/day (95th percentile) overall, 0.21 for premature and 0.19 for term neonates. The statistical and experimental methodology represents an effective strategy for determining exposure and assessing risk. PMID- 26285168 TI - Cell Therapy and Tissue Engineering from and toward the Uterus. AB - Regenerative medicine offers the potential for replacement or repair of different types of cells within damaged tissues or the tissues themselves, typically through cell therapy or tissue engineering. Stem cells are critical to these approaches; indeed, the involvement of bone marrow in the differentiation of stem cells to nonhematopoietic cells is well demonstrated. Further, the contribution of bone marrow-derived stem cells in promoting neoangiogenesis has been demonstrated not only in animal models, but also in human clinical trials with an excellent safety profile. Recent evidence indicates that the endometrium is a tissue with the potential for regeneration through such approaches. The presence of donor cells in the endometrium of women receiving bone marrow transplantation suggests a hematopoietic source with the ability to renew this tissue. Here we describe the role of cell therapy with bone marrow-derived stem cells in treating endometrial dysfunction in Asherman syndrome and/or endometrial atrophy in human and murine models. Additionally, the emerging field of tissue engineering has recently been applied in the reproductive tissues-beyond the endometrium-with elegant studies involving humans and animal models. PMID- 26285169 TI - Endometrial Cancer Stem Cell as a Potential Therapeutic Target. AB - Adult stem cells have recently been identified in several types of mature tissue and it has been also suggested that stem-like cells exist in cancerous tissues. It is believed that many cancer stem cells (CSCs) upregulate the expression of drug transporters, allowing them to efficiently pump antitumor agents out of the cells. CSCs reside in a quiescent state, making them resistant to chemotherapeutic agents that target rapidly cycling cells. They are also endowed with a more invasive and metastatic phenotype. These results indicate the requirement to develop a new target treatment for CSCs. There are several methods for the identification of CSCs; for example, detection by CSC markers, such as CD133, CD44, CD117(c-kit), aldehyde dehydrogenase 1 (ALDH1), and isolation of side population (SP), which are identified based on their ability to remove intracellular Hoechst 33342, a fluorescent dye. Here, we review recent articles that show the presence of stem cells in endometrial cancer and introduce the results of our own recent studies using CD133 or CD117 positive cells and SP cells. PMID- 26285170 TI - Stem Cells in the Uterus: Past, Present and Future. PMID- 26285171 TI - Treatment of allergic rhinitis with intranasal infusion of botulinum toxin type A in mice. AB - AIMS: To determine whether intranasal infusion of botulinum toxin type A (BTX-A) relieves symptoms of ovalbumin (OVA)-induced allergic rhinitis (AR) and reduces nasal inflammation in mice. MAIN METHODS: AR was induced via intraperitoneal injection of OVA followed by daily intranasal challenge with OVA. Five weeks after the initiation of OVA sensitization, nasal cavities were exposed to a single intranasal infusion of BTX-A. The behavior of mice was observed before and 1, 3, 5, 7, 14, 21, and 28days after infusion. Mice were sacrificed after 28days and late histological findings were examined. PBS was administered to control mice. RESULTS: On Day 3, the frequency of typical AR symptoms, including sneezing and nose scratching, significantly decreased in the BTX-A-treated group (n=6) compared to the control group (n=6). Although the AR-inhibiting effects of BTX-A persisted until Day 21, AR symptoms re-appeared in response to daily OVA stimulation. Histological findings of the nasal mucosa also improved following BTX-A administration. Although capillary dilatation and eosinophil infiltration decreased by Day 3, these effects disappeared by Day 28. In contrast, the number and size of the secretary glands in the nasal mucosa did not change following BTX A administration. PBS had no effect on nasal symptoms or histology. CONCLUSIONS: Topical treatment with BTX-A efficiently and temporarily ameliorates AR symptoms. Intranasal infusion does not cause pain or bleeding, and the effects of a single infusion of BTX-A last for at least three weeks. This treatment might be a promising therapeutic strategy for the treatment of AR. PMID- 26285172 TI - Thymoquinone modulates nitric oxide production and improves organ dysfunction of sepsis. AB - AIMS: The present investigation was designed to evaluate the effect of thymoquinone in a septic animal model and to explore the role of nitric oxide (NO) in the process. MAIN METHODS: To achieve this, mice (n=12 per group) were treated in parallel with thymoquinone (0.75mg/kg/day) and/or NG-nitro-l-arginine methyl ester (L-NAME; 400MUg/g/day) prior to sepsis induction with live Escherichia coli. KEY FINDINGS: Thymoquinone significantly improved renal and hepatic functions alone and in combination with L-NAME. This was associated with less NO production and lower oxidative stress in treated animals. Tumor necrosis factor-alpha concentration with thymoquinone and L-NAME were 36.27+/-3.41pg/ml and 56.55+/-5.85pg/ml, respectively, as opposed to 141.11+/-6.46pg/ml in septic controls. Similarly, Interleukin-1alpha, 2, 6 and 10 levels decreased significantly upon treatment with thymoquinone and L-NAME as compared with untreated septic animals. NF-kappaB and NF-kappaB-DNA binding activity in nuclear proteins were also significantly down-regulated. Vascular responsiveness studies in isolated mouse aortae demonstrated a reduced relaxation to acetylcholine exposure in septic mice treated with thymoquinone. SIGNIFICANCE: These findings suggest that thymoquinone prevents sequels of the multiple organ failure syndrome of sepsis by modulating the production of NO and its inflammatory sequela, and adjusting vascular responsiveness. PMID- 26285174 TI - Mesenchymal cells of umbilical cord and umbilical cord blood as a source of human oligodendrocyte progenitors. PMID- 26285173 TI - The anti-angiogenic action of 2-deoxyglucose involves attenuation of VEGFR2 signaling and MMP-2 expression in HUVECs. AB - AIMS: 2-Deoxyglucose (2-DG) is a glucose analogue and has been shown to inhibit angiogenesis in human umbilical vascular endothelial cells (HUVECs) through interference with N-linked glycosylation. However, the anti-angiogenic mechanisms of 2-DG are not fully elucidated. MAIN METHODS: We first employed an ex vivo rat aortic ring model to substantiate the anti-angiogenic action of 2-DG and then used HUVECs to investigate the molecular mechanism underlying such an action. KEY FINDINGS: Results reveal that 2-DG (0.05-1.0mM) significantly inhibited tube formation in both rat aortic rings and HUVECs. 2-DG (0.1-1.0mM) also significantly inhibited cell invasion and migration, as well as the activity and mRNA and protein expression of matrix metalloproteinase (MMP)-2 in HUVECs. In addition, 2-DG (1.0mM) significantly inhibited mRNA and protein expression of vascular endothelial growth receptor 2 (VEGFR2) in a time-dependent manner. 2-DG also significantly inhibited the phosphorylation of the focal adhesion kinase (FAK) and mitogen-activated protein kinase (p38), the downstream molecules of VEGFR2. The effects of 2-DG on tube formation, MMP-2 activity, and VEGFR2 protein expression in HUVECs were reversed by mannose, an N-linked glycosylation precursor. Mannose also reversed 2-DG-induced accumulation of VEGFR2 in the endoplasmic reticulum. SIGNIFICANCE: This ex vivo and in vitro study demonstrates that 2-DG inhibits angiogenesis with an action involving attenuation of VEGFR2 signaling and MMP-2 expression, possibly resulting from interference with N linked glycosylation of VEGFR2. Further studies are needed to show that 2-DG inhibits VEGF-mediated angiogenesis or that the actual status of N-glycosylation of VEGFR2 is affected by the treatment. PMID- 26285175 TI - Chlorogenic acid, a polyphenol in coffee, protects neurons against glutamate neurotoxicity. AB - AIMS: The present study has been designed to explore the molecular mechanism of chlorogenic acid (CGA) in the protective effect against glutamate-induced neuronal cell death. MAIN METHODS: Cortical neurons in primary culture were exposed to 300 MUM l-glutamic acid or vehicle, with or without 10 MUM CGA or 10 MUM MK-801. After 16 h, primary cultures were stained with propidium iodide (PI)/Hoechst or calcein. Double-staining with PI and Hoechst was performed to confirm whether cell death induced by glutamate was apoptotic. In addition, intracellular concentrations of Ca(2+) were observed using Ca(2+) indicator fura 2. KEY FINDINGS: We investigated the protective effects of CGA on glutamate induced neuronal cell death using primary cultures of mouse cerebral cortex because the release of glutamate during brain ischemia triggers death of neurons. Glutamate-induced neuronal cell death was inhibited by treatment with CGA. In addition, CGA prevented the increase in intracellular concentrations of Ca(2+) caused by the addition of glutamate to cultured neurons. On the other hand, there was little effect of CGA on cell death induced by nitric oxide, which is downstream of the ischemic neuronal cell death. Our results suggested that the polyphenol CGA in coffee protects neurons from glutamate neurotoxicity by regulating Ca(2+) entry into neurons. SIGNIFICANCE: CGA in coffee may have clinical benefits for neurodegenerative diseases such as ischemic stroke. PMID- 26285176 TI - Ginsenoside Compound K suppresses the hepatic gluconeogenesis via activating adenosine-5'monophosphate kinase: A study in vitro and in vivo. AB - AIMS: Compound K (CK) is a final intestinal metabolite of protopanaxadiol-type ginsenoside. We have reported that CK presented anti-diabetic effect via diminishing the expressions of hepatic gluconeogenesis key enzyme. Here, we further explore the possible mechanism of CK on suppression hepatic gluconeogenesis via activation of adenosine-5'monophosphate kinase (AMPK) on type 2 diabetes mice in vivo and in HepG2 cells. MAIN METHODS: Type 2 diabetes mice model was developed by high fat diet combined with STZ injection. 30mg/kg/d CK was orally administrated for 4weeks, the fasting blood glucose level and 2h OGTT were conducted, and the protein expression of AMPK, peroxisome proliferator activated receptor-gamma coactivator-1alpha (PGC-1alpha), Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase) were examined. The mechanism of Compound K on hepatic gluconeogenesis was further explored in HepG2 hepatocytes. Glucose production, the protein expression of AMPK, PEPCK, G6pase and PGC-1alpha, hepatic nuclear factor 4alpha (HNF-4alpha) and forkhead transcription factor O1 (FOXO1) were determined after Compound K treatment at the presence of AMPK inhibitor Compound C. KEY FINDINGS: We observed that CK inhibited the expression of PEPCK and G6Pase in the liver and in HepG2 hepatocytes. Meanwhile, CK treatment remarkably increased the activation of AMPK, while decreasing the expressions of PGC-1alpha, HNF-4alpha and FOXO1. However, AMPK inhibitor Compound C could reverse these effects of CK on gluconeogenesis in part. SIGNIFICANCE: The results indicated that the effect of CK on suppression hepatic gluconeogenesis might be via the activation the AMPK activity. PMID- 26285177 TI - High-intensity interval training beneficial effects on body mass, blood pressure, and oxidative stress in diet-induced obesity in ovariectomized mice. AB - AIMS: To investigate the possible beneficial effect of high-intensity interval training (HIIT) on skeletal muscle oxidative stress, body mass (BM) and systolic blood pressure (SBP) in ovariectomized mice fed or not fed a high-fat diet. MAIN METHODS: Three-month-old female C57BL/6 mice were bilaterally ovariectomized (OVX group) or submitted to surgical stress without ovariectomy (SHAM group) and separated into standard chow (SHAM-SC; OVX-SC) and high-fat diet (SHAM-HF; OVX HF) groups. After 13 weeks, an HIIT program (swimming) was carried out for 8 weeks in non-trained (NT) and trained (T) groups. KEY FINDINGS: The significant reduction of uterine mass and the cytological examination of vaginal smears in the OVX group confirmed that ovariectomy was successful. Before the HIIT protocol, the ovariectomized groups showed a greater BM than the SHAM group, irrespective of the diet they received. The HIIT minimized BM gain in animals fed an HF diet and/or ovariectomized. SBP and total cholesterol were increased in the OVX and HF animals compared to their counterparts, and the HIIT efficiently reduced these factors. In the HF and OVX mice, the muscular superoxide dismutase and catalase levels were low while their glutathione peroxidase and glutathione reductase levels were high and the HIIT normalized these parameters. SIGNIFICANCE: Diet-induced obesity maximizes the deleterious effects of an ovariectomy. The HIIT protocol significantly reduced BM, SBP and oxidative stress in the skeletal muscle indicating that HIIT diminishes the cardiovascular and metabolic risk that is inherent to obesity and menopause. PMID- 26285178 TI - Predictors of uterine evacuation following early medical abortion with mifepristone and misoprostol. AB - OBJECTIVES: We sought to determine predictors of uterine evacuation for women undergoing medical abortion using mifepristone and vaginal misoprostol through 63 days' gestation. STUDY DESIGN: We pooled data from two prospective multicenter medical abortion trials. In one study, women received mifepristone 200 mg followed either 6-8 or 23-25 h later by misoprostol 800 mcg vaginally. In the second study, women received mifepristone 200 mg followed either <15 min or 23-25 h later by misoprostol 800 mcg vaginally. We examined the absolute risk (AR) of uterine evacuation using Fisher's Exact Tests for categorical variables and Student t test and Wilcoxon rank-sum tests for continuous variables. We used logistic regression to calculate odds ratios (ORs) of uterine evacuation. RESULTS: Uterine evacuation was performed for 75 (3.5%) of 2160 women. In multivariable analysis, 5 or more prior deliveries (AR 11.9%, OR 4.6) and gestational age of 8 weeks or more (AR 4.1%, OR 2.1) were significantly associated with uterine evacuation, while age of 20 years or younger (AR 1.4%, OR 0.4) was significantly and inversely associated with uterine evacuation. Prior cesarean delivery, multiple gestations, smoking, weight, body surface area and body mass index were not predictive of uterine evacuation in univariate or multivariable analysis. CONCLUSION: Uterine evacuation is an uncommon outcome in medical abortion with mifepristone and vaginal misoprostol. Five or more deliveries are the only significant predictor that identifies a group with an AR of uterine evacuation of more than 6%. IMPLICATIONS: Uterine evacuation is uncommon in medical abortion with mifepristone and vaginal misoprostol. Parity of five or more is the only significant predictor of uterine evacuation exceeding 6%. Until additional research is completed, medical abortion should not be withheld from women with five or more deliveries. PMID- 26285179 TI - The effect of choline-stabilized orthosilicic acid on microelements and silicon concentration, photosynthesis activity and yield of tomato grown under Mn stress. AB - The aim of experiments was to assess the efficiency of choline-stabilized orthosilicic acid (ch-OSA; complex of orthosilicic acid with choline and a bioavailable source of silicon) application under increasing manganese (Mn) stress on the micronutritional composition and yielding of tomato (Solanum lycopersicum L. cvs. 'Alboney F1' and 'Emotion F1'). Plants were grown in rockwool with the application of a nutrient solution varied the Mn concentrations (in mg dm(-3)): 9.6 and 19.2 which cause strong oxidative stress of plants comparing with optimal concentration of that microelement in nutrient solution. The effect of ch-OSA application (at Si concentration of 0.3 mg dm(-3) nutrient solution) was investigated at both Mn-levels. Increasing Mn stress modified the concentration of microelements and silicon (Si) in tomato leaves. Application of ch-OSA also influenced the concentration of nutrients, but the determined changes were generally multidirectional and varied depending on Mn-level and cultivar. Under the increasing Mn stress a significant downward trend was observed for the mean concentration of Fe (in both cultivars) in fruits--but changes of Mn, Zn and Cu were varied depend on cultivar. In the case of cv. 'Alboney F1' ch-OSA application caused an increase the mean concentrations of Fe, Zn and Cu, while in the case of cv. 'Emotion F1' the reduction of mean concentrations of Zn and Cu was recorded. Ch-OSA treatment did not influence on the Mn concentrations in fruits. A beneficial role of ch-OSA was also found in photosynthesis activity. This was especially valid for lower levels of Mn. Application of ch-OSA improved significantly the marketable yield of tomato under stress by a low Mn level. PMID- 26285180 TI - Preoperative progressive explosive-type resistance training is feasible and effective in patients with hip osteoarthritis scheduled for total hip arthroplasty--a randomized controlled trial. AB - OBJECTIVE: To investigate the efficacy and feasibility of progressive explosive type resistance training (RT) in patients with osteoarthritis (OA) of the hip scheduled for total hip arthroplasty (THA). METHOD: Randomized controlled trial (1:1) in patients diagnosed with hip OA and scheduled for THA. The intervention group (IG) performed supervised preoperative progressive explosive-type RT twice a week for 10 weeks; four exercises (hip/thigh) performed in three series each (8 12 repetition maximum). The control group (CG) received 'care as usual'. Efficacy was reported as the between-group difference in the Hip Osteoarthritis Outcome Score (HOOS) (primary endpoint; ADL function), and leg muscle power at post intervention follow-up immediate before surgery. Intention-to-treat analyses were performed in a multilevel regression model adjusting for baseline, sex, age and weight. Feasibility was reported as adherence, exercise related pain and adverse effects. Post-surgical follow up will be reported separately. ClinicalTrials.gov registration: NCT01164111. RESULTS: Eighty patients (age 70.4 +/- 7.6 years, BMI 27.8 +/- 4.6, 52 females (65%) were included. Adherence was high (93%) with acceptable exercise related pain (VAS score <= 5) reported in 83% of sessions and no adverse events. Changes in HOOS 'function' was 10.0 points 95%CI [4.7; 15.3] higher in IG compared to CG (P < 0.001). For all the remaining HOOS subscales IG scored significantly better (P < 0.03) and had higher leg extension muscle power (P < 0.0001) compared to CG. CONCLUSION: Progressive explosive-type RT was feasible in the included group of hip OA patients scheduled for THA and resulted in significant improvement in self-reported outcomes and increased leg muscle power. PMID- 26285181 TI - Density-tapered spiral arrays for ultrasound 3-D imaging. AB - The current high interest in 3-D ultrasound imaging is pushing the development of 2-D probes with a challenging number of active elements. The most popular approach to limit this number is the sparse array technique, which designs the array layout by means of complex optimization algorithms. These algorithms are typically constrained by a few steering conditions, and, as such, cannot guarantee uniform side-lobe performance at all angles. The performance may be improved by the ungridded extensions of the sparse array technique, but this result is achieved at the expense of a further complication of the optimization process. In this paper, a method to design the layout of large circular arrays with a limited number of elements according to Fermat's spiral seeds and spatial density modulation is proposed and shown to be suitable for application to 3-D ultrasound imaging. This deterministic, aperiodic, and balanced positioning procedure attempts to guarantee uniform performance over a wide range of steering angles. The capabilities of the method are demonstrated by simulating and comparing the performance of spiral and dense arrays. A good trade-off for small vessel imaging is found, e.g., in the 60lambda spiral array with 1.0lambda elements and Blackman density tapering window. Here, the grating lobe level is 16 dB, the lateral resolution is lower than 6lambda the depth of field is 120lambda and, the average contrast is 10.3 dB, while the sensitivity remains in a 5 dB range for a wide selection of steering angles. The simulation results may represent a reference guide to the design of spiral sparse array probes for different application fields. PMID- 26285182 TI - Cardiac atrial appendage stem cells engraft and differentiate into cardiomyocytes in vivo: A new tool for cardiac repair after MI. AB - BACKGROUND: This study assessed whether autologous transplantation of cardiac atrial appendage stem cells (CASCs) preserves cardiac function after myocardial infarction (MI) in a minipig model. METHODS AND RESULTS: CASCs were isolated from right atrial appendages of Gottingen minipigs based on high aldehyde dehydrogenase activity and expanded. MI was induced by a 2h snare ligation of the left anterior descending coronary artery. Upon reperfusion, CASCs were intramyocardially injected under NOGA guidance (MI-CASC, n=10). Non-transplanted pigs (MI, n=8) received sham treatment. 3D electromechanical mapping (EMM) and cardiac MRI were performed to assess left ventricular (LV) function. MI pigs developed LV dilatation at 2 months (2M), while in the MI-CASC group volumes remained stable. Global LV ejection fraction decreased by 16 +/- 8% in MI animals vs 3 +/- 10% in MI-CASC animals and regional wall thickening in border areas was better preserved in the MI-CASC group. EMM showed decreased viability and wall motion in the LV for both groups POST-MI, whereas at 2M these parameters only improved in the MI-CASC. Substantial cell retention was accompanied by cardiomyogenic differentiation in 98+/-1% of the transplanted CASCs, which functionally integrated. Second harmonic generation microscopy confirmed the formation of mature sarcomeres in transplanted CASCs. Absence of cardiac arrhythmias indicated the safety of CASC transplantation. CONCLUSION: CASCs preserve cardiac function by extensive engraftment and cardiomyogenic differentiation. Our data indicate the enormous potential of CASCs in myocardial repair. PMID- 26285183 TI - Circulating soluble low-density lipoprotein receptor-related protein 1 (sLRP1) concentration is associated with hypercholesterolemia: A new potential biomarker for atherosclerosis. AB - BACKGROUND: There is clinical interest in identifying novel lipid biomarkers for evaluating cardiovascular risk and targeting lipid-lowering treatment. Low density lipoprotein receptor-related protein 1 (LRP1) plays a crucial role in the dysregulated cholesterol transfer from modified lipoproteins to human coronary vascular smooth muscle cells (hVSMCs), promoting hVSMC-derived foam cell formation. LRP1 has a soluble and circulating form (sLRP1) generated from LRP1. Cholesterol modulates the release of the soluble form of LRP1. Using in vitro, ex vivo and patient-based approaches, we tested the association between circulating sLRP1 concentrations and hypercholesterolemia and the potential of sLRP1 as a biomarker of atherosclerosis. METHODS AND RESULTS: Circulating sLRP1 concentrations were higher in severe hypercholesterolemia compared to moderate hypercholesterolemia or normocholesterolemia (Study 1). Circulating sLRP1 was significantly associated with established pro-atherogenic lipid parameters in two different hypercholesterolemic populations (Studies 2 and 3). sLRP1 concentrations decreased after statin treatment and increased after statin withdrawal (Study 3). In vitro experiments showed that native LDL, aggregated LDL and VLDL+IDL lipoproteins induced the release of sLRP1 from hVSMC. sLRP1 levels were increased in the conditioned medium of coronary atherosclerotic plaque areas extracted from patients compared to non-atherosclerotic areas of the same coronary artery and patient. Circulating sLRP1 concentrations were independently associated with the occurrence of carotid atherosclerosis in a hypercholesterolemic population (Study 2). The later association was higher than that observed for other classical or novel lipid parameters. CONCLUSIONS: Circulating sLRP1 is a new lipid-related parameter potentially useful as a biomarker for atherosclerosis. PMID- 26285184 TI - Reply to the letter "Post-ischemic myocardial stunning was the starting point of takotsubo syndrome: Restitution is justified after falling down on". PMID- 26285185 TI - Reducing the economic burden of chronic disease requires major investment in public health. PMID- 26285186 TI - Variation across Canada in the economic burden attributable to excess weight, tobacco smoking and physical inactivity. AB - OBJECTIVES: Tobacco smoking, excess weight and physical inactivity contribute substantially to the preventable disease burden in Canada. The purpose of this paper is to determine the potential reduction in economic burden if all provinces achieved prevalence rates of these three risk factors (RFs) equivalent to those of the province with the lowest rates, and to update and address a limitation noted in our previous model. METHODS: We used a previously developed approach based on population attributable fractions to estimate the economic burden associated with these RFs. Sex-specific relative risk and age-/sex-specific prevalence data were used in the modelling. The previous model was updated using the most current data for developing resource allocation weights. RESULTS: In 2012, the prevalence of tobacco smoking, excess weight and physical inactivity was the lowest in British Columbia. If age- and sex-specific prevalence rates from BC were applied to populations living in the other provinces, the annual economic burden attributable to these three RFs would be reduced by $5.3 billion. Updating the model resulted in a considerable shift in economic burden from smoking to excess weight, with the estimated annual economic burden attributable to excess weight now 25% higher compared to that of tobacco smoking ($23.3 vs. $18.7 billion). CONCLUSION: Achieving RF prevalence rates equivalent to those of the province with the lowest rates would result in a 10% reduction in economic burden attributable to excess weight, smoking and physical inactivity in Canada. This study shows that using current resource use data is important for this type of economic modelling. PMID- 26285187 TI - Physical activity and sedentary behaviour of toddlers and preschoolers in child care centres in Alberta, Canada. AB - OBJECTIVE: To describe duration of physical activity and duration and bouts of sedentary behaviour during child care in a sample of toddlers and preschoolers (19-60 months) from Alberta, Canada, and to examine whether duration and bouts differed among sex, age and parental immigration status groups. METHODS: One hundred and fourteen children aged 19-60 months from eight child care centres throughout Alberta participated. Data were collected at baseline of a study examining revised Alberta Child Care Accreditation Standards. Duration of physical activity (light (LPA), moderate-to-vigorous (MVPA)) and duration and bouts (1-4, 5-9, 10-14, and >=15 minutes) of sedentary behaviour during child care were accelerometer-derived using 15-second epochs during October/November, 2013. Median [Interquartile ranges] and ANOVAs, accounting for the clustered nature of the data, were calculated. RESULTS: Minutes/hour spent in sedentary behaviour, LPA and MVPA were 36.9 [32.9, 40.7], 18.4 [16.0, 20.9] and 4.2 [2.5, 5.6] respectively. Frequency/hour of sedentary bouts lasting 1-4, 5-9, 10-14 and >=15 mins were 6.7 [6.1, 7.6], 0.9 [0.6, 1.1], 0.4 [0.2, 0.5] and 0.3 [0.2, 0.4] respectively. Preschoolers participated in less sedentary behaviour and more LPA and MVPA, and had fewer sedentary bouts lasting 10-14 and >=15 mins compared to toddlers (p < 0.05). CONCLUSION: This is the first Canadian study to report on the duration of physical activity and duration and bouts of sedentary behaviour among both toddlers and preschoolers attending child care centres. These findings suggest child care interventions are needed to increase MVPA and decrease total sedentary behaviour while continuing to promote short sedentary bouts. PMID- 26285188 TI - Between a rock and a hard place: Smoking trends in a Manitoba First Nation. AB - OBJECTIVES: The purpose of this study is to estimate and compare smoking prevalence over two time periods in a Manitoba First Nation community. METHODS: Data fromtwo independent Diabetes Screening Studies in Sandy Bay First Nation, collected in 2002/2003 (n = 482) and 2011/2012 (n = 596),were used. Crude prevalence of current and ever smoking as well as current smoke exposure was estimated. Change over time was tested using a chi2 statistic. RESULTS: The crude prevalence of current smoking was 74.0% (95% confidence interval [CI]: 70.1, 78.0) in 2002/2003 and 80.0% (95% CI: 76.8, 83.2) in 2011/2012. The crude prevalence of ever smoking was 83.0% in 2002/2003 and 91.4% in 2011/2012. The prevalence of both current smoking status and ever smoking were significantly higher in 2011/2012 compared to 2002/2003 (p = 0.020 and p < 0.001 respectively). Among participants who were not current smokers, 58.5% (95% CI: 49.6, 67.4) and 76.5% (95% CI: 68.9, 84.1) reported at least one person who smoked in the home in 2002/2003 and 2011/2012 respectively (p = 0.003). In 2011/2012, 96.5% (95% CI: 94.8, 98.2) of those who reported having any children under the age of 18 living in the home were either a current smoker and/or reported that someone else smoked in the home. CONCLUSION: Public health and policy initiatives are needed to address the increase in smoking prevalence in the study community. PMID- 26285189 TI - Engaging community organizations in falls prevention for older adults: Moving from research to action. AB - OBJECTIVES: Falls prevention (FP) evidence abounds but falls rates remain relatively unaffected. This study aimed to explore community service providers' use of evidence-based FP interventions, attitudes toward implementation, knowledge and capacity for FP engagement, collaboration in FP, and organizational readiness to implement evidence. To our knowledge, this is the first study exploring the potential for broader integration of FP throughout communities. METHODS: A purposive sampling of providers (n = 84), in varied roles within diverse senior-serving community organizations (both health and non-health sectors) across disparate geographies, completed a structured survey as part of a larger mixed methods study. RESULTS: Nearly all (90%) reported already implementing at least one evidence-based FP practice. The majority indicated that falls were preventable (82%) and a top concern for older adults (75%), and that FP would be beneficial to their clients (75%). There were, however, notable differences between health and non-health sectors in their: confidence in providing FP activities (86% vs. 47%), desire for future collaboration (86% vs. 56%) and already knowing how best to provide FP activities (49% vs. 36%). Only some (21%) perceived that staff to a great extent had the necessary knowledge and skills, and few (10%) perceived that available resources could support FP activities. CONCLUSION: Community service providers generally supported FP, but resources limited implementation, particularly in non-health sectors. Translating FP evidence to better fit community settings, and fostering collaboration to bridge resource gaps, suggest a public health role in the broader integration of FP within and across community sectors. PMID- 26285190 TI - Risk perception, psychological heuristics and the water fluoridation controversy. AB - OBJECTIVES: Increasingly, support for water fluoridation has come under attack. We seek an explanation, focusing on the case of Waterloo, Ontario, where a 2010 referendum overturned its water fluoridation program. In particular, we test whether individuals perceive the risks of water fluoridation based not on 'hard' scientific evidence but on heuristics and cultural norms. METHODS: A sample of 376 residents in Waterloo were surveyed in June 2012 using random digit dialing. We use factor analysis, OLS regression, as well as t-tests to evaluate a survey experiment to test the credibility hypothesis. RESULTS: Perceptions of fluoride as a risk are lower among those who perceive fluoride's benefits (B = .473, p < 0.001) and those whose cultural view is 'egalitarian' (B = .156, p < 0.05). The experiment shows a lower level of perception of fluoride's benefits among respondents who are told that water fluoridation is opposed by a national advocacy group (Group A) compared to those who are told that the government and the World Health Organization support fluoridation (Group B) (t = 1.6547, p < 0.05), as well as compared to the control group (t = 1.8913, p < 0.05). There is no difference between Group B and the control, possibly because people's already general support for fluoridation is less prone to change when told that other public organizations also support fluoridation. CONCLUSION: Public health officials should take into account cultural norms and perceptions when individuals in a community appear to rise up against water fluoridation, with implications for other public health controversies. PMID- 26285191 TI - An adaptation of the Yesterday Method to correct for under-reporting of alcohol consumption and estimate compliance with Canadian low-risk drinking guidelines. AB - OBJECTIVES: To estimate compliance with Canada's Low-Risk Alcohol Drinking Guidelines (LRDG) in different groups of drinkers after adjusting for underreporting of alcohol use, and to identify which types of beverage are more likely to be consumed when LRDGs are exceeded. METHOD: Our sample consisted of 43,242 Canadians aged 15 and over who had responded to the Canadian Alcohol and Drug Use Monitoring Survey, 2008-2010. Consumption in excess of LRDG was estimated for subgroups of drinkers after adjustment for under-reporting of consumption. Responses to Beverage-Specific Yesterday questions were used to make age-, gender- and beverage-specific corrections to under-reporting for data from the last 12 months Quantity-Frequency questions. Statistics Canada data on sales of beer, wine and spirits were also incorporated into the adjusted calculations. RESULTS: After adjustment for under-reporting, non-compliance with weekly LRDG limits to reduce risk of long-term harm increased from 6.8% to 27.3% among drinkers, and from 42.3% to 68.3% with respect to drinks. Non-compliance with daily LRDG limits to reduce risk of short-term harm increased from 16.7% to 38.6% among drinkers, and from 53.3% to 80.5% with respect to drinks. After adjustment, over 92% of total consumption occurred on risky drinking days among underage Canadians and over 91% of consumption reported by young adults took place during risky drinking occasions. Wine was least likely to be drunk in a risky fashion, spirits were the most likely. CONCLUSION: When corrections for under-reporting are made, most Canadian alcohol consumption occurs on days when national LRDG are exceeded, especially for underage and young adult drinkers. PMID- 26285192 TI - The impact of policies to reduce blood glucose test strip utilization and costs in Canada. AB - OBJECTIVES: Several strategies have been proposed to manage the utilization of blood glucose test strips (BGTS) in Canada; however their potential impacts on utilization and costs of publically funded test strips are unknown. METHODS: We investigated the impact of three potential policies that would restrict the number of test strips reimbursed by the public drug plans in Ontario and British Columbia (BC), and incorporated negotiated price reductions. These policies were based on recommendations from the Canadian Agency for Drugs and Technologies in Health, a briefing document by the Canadian Diabetes Association, and a new policy introduced by the Ontario Ministry of Health and Long-Term Care. BGTS utilization rates were assessed in two cross-sectional analyses among adults aged 18 years or older in BC and 65 or older in Ontario who received publicly-funded BGTS between January 2004 and December 2012. We modeled the 5-year utilization and cost implications of the three policies using time-series analysis. RESULTS: In 2012, there were 317,130 test strip recipients in Ontario and 136,659 recipients in BC, at a cost of $104.4 million and $22.6 million respectively. Under the scenarios of reduced BGTS quantities, 5-year cost savings ranged between $98.8 million (18.2% reduction) and $224.1 million (41.4% reduction) in Ontario and between $23.1 million (19.2% reduction) and $51.1 million (42.4% reduction) in BC. Price reductions of 15% resulted in annual savings of $14.4 million (13.7% reduction) in Ontario and $3.4 million (14.1% reduction) in BC. CONCLUSIONS: Policies that align with evidence and expert guidance could impart substantial cost savings in multiple jurisdictions despite different public drug plans. PMID- 26285193 TI - Breastfeeding as a means to prevent infant morbidity and mortality in Aboriginal Canadians: A population prevented fraction analysis. AB - OBJECTIVES: Canadian Aboriginal infants experience poor health compared with other Canadian infants. Breastfeeding protects against many infant infections that Canadian Aboriginals disproportionately experience. The objective of our research was to estimate the proportion of select infant infection and mortality outcomes that could be prevented if all Canadian Aboriginal infants were breastfed. METHODS: We used Levin's formula to estimate the proportion of three infectious outcomes and one mortality outcome that could be prevented in infancy by breastfeeding. Estimates were calculated for First Nations (both on- and off reserve), Metis and Inuit as well as all Canadian infants for comparison. We extracted prevalence estimates of breastfeeding practices from national population-based surveys. We extracted relative risk estimates from published meta-analyses. RESULTS: Between 5.1% and 10.6% of otitis media, 24.3% and 41.4% of gastrointestinal infection, 13.8% and 26.1% of hospitalizations from lower respiratory tract infections, and 12.9% and 24.6% of sudden infant death could be prevented in Aboriginal infants if they received any breastfeeding. CONCLUSION: Interventions that promote, protect and support breastfeeding may prevent a substantial proportion of infection and mortality in Canadian Aboriginal infants. PMID- 26285194 TI - [Gender, age, occupation, economic sector and mental health in the workplace: the results of the study SALVEO]. AB - OBJECTIVES: This article examined the contribution of gender, age, occupation and economic sector on psychological distress, depression and burnout. METHODS: The data came from the SALVEO study carried out in 2009- 2012 among 2,162 workers employed in 63 Canadian workplaces. Multilevel logistic regression models were estimated on the total sample and separately for men and women. RESULTS: The prevalences of psychological distress, depression and burnout were 23.8%, 5.8% and 3.9% respectively. Mental health problems varied between workplaces, but variations between workplaces were stronger for burnout. Differences between men and women were significant only for psychological distress, depression, and emotional exhaustion. Unskilled workers were found more at risk for depression and burnout. Associations among age, occupation and economic sector were not the same between genders. CONCLUSION: Results from the SALVEO study highlight important mental health problems in workers that vary between workplaces, and that differences in symptomatology are associated with gender, age, occupation and economic sector. Gender reveals differentiated profiles of relationships. These results point towards the development of targeted approaches to the prevention of and intervention on mental health problems in workplaces. PMID- 26285195 TI - "If they tell me to get it, I'll get it. If they don't...": Immunization decision making processes of immigrant mothers. AB - OBJECTIVE: To understand information-gathering and decision-making processes of immigrant mothers for scheduled childhood vaccines, vaccination during pregnancy, seasonal flu and pandemic vaccination. METHODS: We conducted 23 qualitative semi structured interviews with immigrated mothers from Bhutanese refugee, South Asian and Chinese communities. Participants lived in Edmonton, Alberta and had at least one child under eight years old. Using NVivo qualitative software, we generated an inductive coding scheme through content analysis of interview transcripts. RESULTS: Our three main findings on information gathering and use in vaccination decisions were: 1) participants in all three communities passively received immunization information. Most mothers learned about vaccine practices exclusively from health care practitioners during scheduled visits. Social networks were primary sources of information in origin countries but were lost during immigration to Canada; 2) participants demonstrated universal trust in vaccines (i.e., no anti-vaccination sentiment). They were comfortable in receiving vaccines for themselves and their children, regardless of past adverse reactions; 3) participants' recollection of the H1N1 vaccination campaign was almost nil, demonstrating the lack of reach of public health vaccination campaigns to designated priority groups (pregnant women and children) in Alberta. CONCLUSION: Our results highlight the limitations of Alberta's current vaccination communication strategies in reaching immigrant women. When immigrant mothers receive vaccination information, our results indicate they will likely follow recommendations. However, our study shows that current communication strategies are not making this information accessible to immigrant women, which limits their ability to make informed vaccination decisions for themselves and their children. PMID- 26285197 TI - Governing population screening in an age of expansion: The case of newborn screening. AB - Newborn bloodspot screening is one of the most enduring and successful population screening initiatives. Yet technological innovation to permit simultaneous measurement of multiple biomarkers - and potentially, entire genomes - has spurred expansion and debate. Through a cross-jurisdictional comparison, we describe the varied roles and reach of screening-related governance structures in the United States, the United Kingdom, New Zealand and Canada, and highlight the distinct values and resources brought to bear by the genetics, public health and maternal-child health communities in adjudicating the benefits and burdens of expanded newborn screening. We call for the expansion of formal governance structures that are balanced in resources and perspective and mandated to ensure that the organization and delivery of newborn screening achieves optimal quality. PMID- 26285196 TI - Skin deep: Coverage of skin cancer and recreational tanning in Canadian women's magazines (2000-2012). AB - OBJECTIVE: Skin cancer is a significant public health problem among Canadians. Knowledge and attitudes about health are informed by mass media. The aim of our study was to describe the volume and nature of coverage of skin cancer and recreational tanning in Canadian women's magazines. METHODS: Directed content analysis on article text and images in six popular Canadian women's magazines (Chatelaine, Canadian Living, Homemakers, Flare, FASHION, ELLE Canada) from 2000 2012 with attention to risk factors, ultraviolet radiation (UV) exposure and protection behaviours, and early detection. Six popular American women's magazines were used for a between-country comparison. RESULTS: There were 154 articles (221 images) about skin cancer and tanning published over 13 years. Volume of coverage did not increase in a linear fashion over time. The most common risk factor reported on was UV exposure (39%), with other risk factors less frequently identified. Although 72% of articles promoted sunscreen use, little content encouraged other protection behaviours. Only 15% of articles and 1% of images discouraged indoor tanning, while 41% of articles and 53% of images promoted the tanned look as attractive. Few articles (<11%) reported on early detection. Relative to American magazines, Canadian magazines had a greater proportion of content that encouraged sunscreen use and promoted the tanned look and a lesser proportion of content on risk factors and early detection. CONCLUSION: Skin cancer and tanning messages in Canadian women's magazines had a narrow focus and provided limited information on risk factors or screening. Conflicting messages about prevention (text vs. images) may contribute to harmful UV behaviours among Canadian women. PMID- 26285198 TI - The Trans-Pacific Partnership Agreement: Trading away our health? AB - There is long-standing interest by the public health community in the potential implications of trade and investment agreements for public health. Our commentary highlights the main pathways by which the Trans-Pacific Partnerships (TPP), a comprehensive trade and investment agreement currently under negotiation, might undermine population health (based on analysis of and commentary about leaked chapters of the TPP), and calls for a more transparent and health-sensitive TPP negotiation process. We argue that use of comprehensive health impact assessments could be helpful in identifying how the potentially serious health consequences of the TPP and similar future international trade and investment agreements can be avoided, minimized or mitigated. PMID- 26285199 TI - Population health promotion 2.0: An eco-social approach to public health in the Anthropocene. AB - Humanity is both an animal species that evolved within and is dependent upon natural ecosystems and a social animal that exists within the social systems we have created. Our health is dependent upon both these systems - natural and social - functioning well, and indeed upon their interactions. Yet our approach to improving the health of the population over the past few decades has been largely, if not exclusively, focused on the social determinants of health. A recent Canadian Public Health Association (CPHA) Discussion Document and the technical report on which it is based seek to strike a more balanced approach. First, they document the dramatic and rapid global ecological changes that humans have created and argue that they are a significant threat to the health of the population in the 21st century. Second, they identify the underlying social, cultural and economic forces that are driving these changes. Third, they argue that we need to take an eco-social approach in population health promotion, recognizing the interactions between the ecological and social determinants of health. Such an approach could be considered to be 'Population health promotion 2.0', and it has profound implications for the practice of public health. PMID- 26285200 TI - Missed opportunity to explore social determinants of health and protective properties in First Nations study. PMID- 26285201 TI - Design and Testing of a Bionic Dancing Prosthesis. AB - Traditionally, prosthetic leg research has focused on improving mobility for activities of daily living. Artistic expression such as dance, however, is not a common research topic and consequently prosthetic technology for dance has been severely limited for the disabled. This work focuses on investigating the ankle joint kinetics and kinematics during a Latin-American dance to provide unique motor options for disabled individuals beyond those of daily living. The objective of this study was to develop a control system for a bionic ankle prosthesis that outperforms conventional prostheses when dancing the rumba. The biomechanics of the ankle joint of a non-amputee, professional dancer were acquired for the development of the bionic control system. Subsequently, a professional dancer who received a traumatic transtibial amputation in April 2013 tested the bionic dance prosthesis and a conventional, passive prosthesis for comparison. The ability to provide similar torque-angle behavior of the biological ankle was assessed to quantify the biological realism of the prostheses. The bionic dancing prosthesis overlapped with 37 +/- 6% of the non amputee ankle torque and ankle angle data, compared to 26 +/- 2% for the conventional, passive prosthesis, a statistically greater overlap (p = 0.01). This study lays the foundation for quantifying unique, expressive activity modes currently unavailable to individuals with disabilities. Future work will focus on an expansion of the methods and types of dance investigated in this work. PMID- 26285202 TI - Microbial Communities Can Be Described by Metabolic Structure: A General Framework and Application to a Seasonally Variable, Depth-Stratified Microbial Community from the Coastal West Antarctic Peninsula. AB - Taxonomic marker gene studies, such as the 16S rRNA gene, have been used to successfully explore microbial diversity in a variety of marine, terrestrial, and host environments. For some of these environments long term sampling programs are beginning to build a historical record of microbial community structure. Although these 16S rRNA gene datasets do not intrinsically provide information on microbial metabolism or ecosystem function, this information can be developed by identifying metabolisms associated with related, phenotyped strains. Here we introduce the concept of metabolic inference; the systematic prediction of metabolism from phylogeny, and describe a complete pipeline for predicting the metabolic pathways likely to be found in a collection of 16S rRNA gene phylotypes. This framework includes a mechanism for assigning confidence to each metabolic inference that is based on a novel method for evaluating genomic plasticity. We applied this framework to 16S rRNA gene libraries from the West Antarctic Peninsula marine environment, including surface and deep summer samples and surface winter samples. Using statistical methods commonly applied to community ecology data we found that metabolic structure differed between summer surface and winter and deep samples, comparable to an analysis of community structure by 16S rRNA gene phylotypes. While taxonomic variance between samples was primarily driven by low abundance taxa, metabolic variance was attributable to both high and low abundance pathways. This suggests that clades with a high degree of functional redundancy can occupy distinct adjacent niches. Overall our findings demonstrate that inferred metabolism can be used in place of taxonomy to describe the structure of microbial communities. Coupling metabolic inference with targeted metagenomics and an improved collection of completed genomes could be a powerful way to analyze microbial communities in a high-throughput manner that provides direct access to metabolic and ecosystem function. PMID- 26285203 TI - The Therapeutic Effect of Pamidronate on Lethal Avian Influenza A H7N9 Virus Infected Humanized Mice. AB - A novel avian influenza virus H7N9 infection occurred among human populations since 2013. Although the lack of sustained human-to-human transmission limited the epidemics caused by H7N9, the late presentation of most patients and the emergence of neuraminidase-resistant strains made the development of novel antiviral strategy against H7N9 in urgent demands. In this study, we evaluated the potential of pamidronate, a pharmacological phosphoantigen that can specifically boost human Vdelta2-T-cell, on treating H7N9 virus-infected humanized mice. Our results showed that intraperitoneal injection of pamidronate could potently decrease the morbidity and mortality of H7N9-infected mice through controlling both viral replication and inflammation in affected lungs. More importantly, pamidronate treatment starting from 3 days after infection could still significantly ameliorate the severity of diseases in infected mice and improve their survival chance, whereas orally oseltamivir treatment starting at the same time showed no therapeutic effects. As for the mechanisms underlying pamidronate-based therapy, our in vitro data demonstrated that its antiviral effects were partly mediated by IFN-gamma secreted from human Vdelta2-T cells. Meanwhile, human Vdelta2-T cells could directly kill virus-infected host cells in a perforin-, granzyme B- and CD137-dependent manner. As pamidronate has been used for osteoporosis treatment for more than 20 years, pamidronate-based therapy represents for a safe and readily available option for clinical trials to treat H7N9 infection. PMID- 26285204 TI - Detailed Functional and Proteomic Characterization of Fludarabine Resistance in Mantle Cell Lymphoma Cells. AB - Mantle cell lymphoma (MCL) is a chronically relapsing aggressive type of B-cell non-Hodgkin lymphoma considered incurable by currently used treatment approaches. Fludarabine is a purine analog clinically still widely used in the therapy of relapsed MCL. Molecular mechanisms of fludarabine resistance have not, however, been studied in the setting of MCL so far. We therefore derived fludarabine resistant MCL cells (Mino/FR) and performed their detailed functional and proteomic characterization compared to the original fludarabine sensitive cells (Mino). We demonstrated that Mino/FR were highly cross-resistant to other antinucleosides (cytarabine, cladribine, gemcitabine) and to an inhibitor of Bruton tyrosine kinase (BTK) ibrutinib. Sensitivity to other types of anti lymphoma agents was altered only mildly (methotrexate, doxorubicin, bortezomib) or remained unaffacted (cisplatin, bendamustine). The detailed proteomic analysis of Mino/FR compared to Mino cells unveiled over 300 differentially expressed proteins. Mino/FR were characterized by the marked downregulation of deoxycytidine kinase (dCK) and BTK (thus explaining the observed crossresistance to antinucleosides and ibrutinib), but also by the upregulation of several enzymes of de novo nucleotide synthesis, as well as the up-regulation of the numerous proteins of DNA repair and replication. The significant upregulation of the key antiapoptotic protein Bcl-2 in Mino/FR cells was associated with the markedly increased sensitivity of the fludarabine-resistant MCL cells to Bcl-2 specific inhibitor ABT199 compared to fludarabine-sensitive cells. Our data thus demonstrate that a detailed molecular analysis of drug-resistant tumor cells can indeed open a way to personalized therapy of resistant malignancies. PMID- 26285206 TI - The Distribution of Cool Spots as Microrefugia in a Mountainous Area. AB - It has recently been proposed that microrefugia played an important role in species survival during past climate change events. However, the current distributions of microrefugia remain largely unknown. Wind-hole sites are areas affected by preferential flows of cool air generated in interstitial spaces created by rock fragments or colluvia. Alpine plant species occurring in lowland wind-hole sites isolated from alpine zones may be relicts of the last glacial period. Hokkaido, northern Japan, is known to contain many wind-hole sites in which alpine plant species can occur. Here we surveyed 55 wind-hole sites in the Kitami region, eastern Hokkaido, and observed two alpine plant species (lingonberry, Vaccinium vitis-idaea, and Labrador tea, Rhododendron groenlandicum ssp. diversipilosum var. diversipilosum) in 14 wind-hole sites. Statistical modeling showed that wind-hole sites are likely to occur in areas with high maximum slope angles and volcanic rock cover, and concave surfaces. Our predictions of wind-hole site distributions suggest that such topographic conditions are common in our study area, and that many undiscovered wind-hole sites exist. Ignoring microhabitats may greatly underestimate species distributions in topographically complex regions, and dispersed cool spots may also function as stepping stones and temporal habitats for cold-adapted species. Because these localized unique habitats usually occur in economically unproductive sites, identifying and protecting potential microrefugia (cool spots) would be a robust and cost-effective mitigation of climate change impacts. PMID- 26285205 TI - High Efficacy but Low Potency of delta-Opioid Receptor-G Protein Coupling in Brij 58-Treated, Low-Density Plasma Membrane Fragments. AB - PRINCIPAL FINDINGS: HEK293 cells stably expressing PTX-insensitive delta-opioid receptor-Gi1alpha (C351I) fusion protein were homogenized, treated with low concentrations of non-ionic detergent Brij-58 at 0 degrees C and fractionated by flotation in sucrose density gradient. In optimum range of detergent concentrations (0.025-0.05% w/v), Brij-58-treated, low-density membranes exhibited 2-3-fold higher efficacy of DADLE-stimulated, high-affinity [32P]GTPase and [35S]GTPgammaS binding than membranes of the same density prepared in the absence of detergent. The potency of agonist DADLE response was significantly decreased. At high detergent concentrations (>0.1%), the functional coupling between delta-opioid receptors and G proteins was completely diminished. The same detergent effects were measured in plasma membranes isolated from PTX-treated cells. Therefore, the effect of Brij-58 on delta-opioid receptor-G protein coupling was not restricted to the covalently bound Gi1alpha within delta-opioid receptor-Gi1alpha fusion protein, but it was also valid for PTX-sensitive G proteins of Gi/Go family endogenously expressed in HEK293 cells. Characterization of the direct effect of Brij-58 on the hydrophobic interior of isolated plasma membranes by steady-state anisotropy of diphenylhexatriene (DPH) fluorescence indicated a marked increase of membrane fluidity. The time-resolved analysis of decay of DPH fluorescence by the "wobble in cone" model of DPH motion in the membrane indicated that the exposure to the increasing concentrations of Brij-58 led to a decreased order and higher motional freedom of the dye. SUMMARY: Limited perturbation of plasma membrane integrity by low concentrations of non-ionic detergent Brij-58 results in alteration of delta-OR-G protein coupling. Maximum G protein-response to agonist stimulation (efficacy) is increased; affinity of response (potency) is decreased. The total degradation plasma membrane structure at high detergent concentrations results in diminution of functional coupling between delta-opioid receptors and G proteins. PMID- 26285207 TI - IL-22 Protects against Tissue Damage during Cutaneous Leishmaniasis. AB - Cutaneous leishmaniasis is a disease characterized by ulcerating skin lesions, the resolution of which requires an effective, but regulated, immune response that limits parasite growth without causing permanent tissue damage. While mechanisms that control the parasites have been well studied, the factors regulating immunopathologic responses are less well understood. IL-22, a member of the IL-10 family of cytokines, can contribute to wound healing, but in other instances promotes pathology. Here we investigated the role of IL-22 during leishmania infection, and found that IL-22 limits leishmania-induced pathology when a certain threshold of damage is induced by a high dose of parasites. Il22-/ mice developed more severe disease than wild-type mice, with significantly more pathology at the site of infection, and in some cases permanent loss of tissue. The increased inflammation was not due to an increased parasite burden, but rather was associated with the loss of a wound healing phenotype in keratinocytes. Taken together, these studies demonstrate that during cutaneous leishmaniasis, IL-22 can play a previously unappreciated role in controlling leishmania-induced immunopathology. PMID- 26285208 TI - Development and Validation of a Miniature Programmable tDCS Device. AB - Research is being conducted on the use of transcranial direct current stimulation (tDCS) for therapeutic effects, and also on the mechanisms through which such therapeutic effects are mediated. A bottleneck in the progress of the research has been the large size of the existing tDCS systems which prevents subjects from performing their daily activities. To help research into the principles, mechanisms, and benefits of tDCS, reduction of size and weight, improvement in simplicity and user friendliness, portability, and programmability of tDCS systems are vital. This paper presents a design for a low-cost, light-weight, programmable, and portable tDCS device. The device is head-mountable and can be concealed in a hat and worn on the head by the subject while receiving the stimulation. The strength of the direct current stimulation can be selected through a simple user interface. The device is constructed and its performance evaluated through bench and in vivo tests. The tests validated the operation of the device in inducing neuromodulatory changes in primary motor cortex, M1, through measuring excitability of dominant M1 of resting right first dorsal interosseus muscle by transcranial magnetic stimulation induced motor evoked potentials. It was observed that the tDCS device induced comparable neuromodulatory effects in M1 as the existing bulky tDCS systems. PMID- 26285209 TI - MORPHEUS, a Webtool for Transcription Factor Binding Analysis Using Position Weight Matrices with Dependency. AB - Transcriptional networks are central to any biological process and changes affecting transcription factors or their binding sites in the genome are a key factor driving evolution. As more organisms are being sequenced, tools are needed to easily predict transcription factor binding sites (TFBS) presence and affinity from mere inspection of genomic sequences. Although many TFBS discovery algorithms exist, tools for using the DNA binding models they generate are relatively scarce and their use is limited among the biologist community by the lack of flexible and user-friendly tools. We have developed a suite of web tools (called Morpheus) based on the proven Position Weight Matrices (PWM) formalism that can be used without any programing skills and incorporates some unique features such as the presence of dependencies between nucleotides positions or the possibility to compute the predicted occupancy of a large regulatory region using a biophysical model. To illustrate the possibilities and simplicity of Morpheus tools in functional and evolutionary analysis, we have analysed the regulatory link between LEAFY, a key plant transcription factor involved in flower development, and its direct target gene APETALA1 during the divergence of Brassicales clade. PMID- 26285210 TI - Influence of Feature Encoding and Choice of Classifier on Disease Risk Prediction in Genome-Wide Association Studies. AB - Various attempts have been made to predict the individual disease risk based on genotype data from genome-wide association studies (GWAS). However, most studies only investigated one or two classification algorithms and feature encoding schemes. In this study, we applied seven different classification algorithms on GWAS case-control data sets for seven different diseases to create models for disease risk prediction. Further, we used three different encoding schemes for the genotypes of single nucleotide polymorphisms (SNPs) and investigated their influence on the predictive performance of these models. Our study suggests that an additive encoding of the SNP data should be the preferred encoding scheme, as it proved to yield the best predictive performances for all algorithms and data sets. Furthermore, our results showed that the differences between most state-of the-art classification algorithms are not statistically significant. Consequently, we recommend to prefer algorithms with simple models like the linear support vector machine (SVM) as they allow for better subsequent interpretation without significant loss of accuracy. PMID- 26285211 TI - Experimental Transmission of Karshi (Mammalian Tick-Borne Flavivirus Group) Virus by Ornithodoros Ticks >2,900 Days after Initial Virus Exposure Supports the Role of Soft Ticks as a Long-Term Maintenance Mechanism for Certain Flaviviruses. AB - BACKGROUND: Members of the mammalian tick-borne flavivirus group, including tick borne encephalitis virus, are responsible for at least 10,000 clinical cases of tick-borne encephalitis each year. To attempt to explain the long-term maintenance of members of this group, we followed Ornithodoros parkeri, O. sonrai, and O. tartakovskyi for >2,900 days after they had been exposed to Karshi virus, a member of the mammalian tick-borne flavivirus group. METHODOLOGY/PRINCIPAL FINDINGS: Ticks were exposed to Karshi virus either by allowing them to feed on viremic suckling mice or by intracoelomic inoculation. The ticks were then allowed to feed individually on suckling mice after various periods of extrinsic incubation to determine their ability to transmit virus by bite and to determine how long the ticks would remain infectious. The ticks remained efficient vectors of Karshi virus, even when tested >2,900 d after their initial exposure to virus, including those ticks exposed to Karshi virus either orally or by inoculation. CONCLUSIONS/SIGNIFICANCE: Ornithodoros spp. ticks were able to transmit Karshi virus for >2,900 days (nearly 8 years) after a single exposure to a viremic mouse. Therefore, these ticks may serve as a long-term maintenance mechanism for Karshi virus and potentially other members of the mammalian tick-borne flavivirus group. PMID- 26285212 TI - Facial Emotion Recognition in Parkinson's Disease: An fMRI Investigation. AB - BACKGROUND: Findings of behavioral studies on facial emotion recognition in Parkinson's disease (PD) are very heterogeneous. Therefore, the present investigation additionally used functional magnetic resonance imaging (fMRI) in order to compare brain activation during emotion perception between PD patients and healthy controls. METHODS AND FINDINGS: We included 17 nonmedicated, nondemented PD patients suffering from mild to moderate symptoms and 22 healthy controls. The participants were shown pictures of facial expressions depicting disgust, fear, sadness, and anger and they answered scales for the assessment of affective traits. The patients did not report lowered intensities for the displayed target emotions, and showed a comparable rating accuracy as the control participants. The questionnaire scores did not differ between patients and controls. The fMRI data showed similar activation in both groups except for a generally stronger recruitment of somatosensory regions in the patients. CONCLUSIONS: Since somatosensory cortices are involved in the simulation of an observed emotion, which constitutes an important mechanism for emotion recognition, future studies should focus on activation changes within this region during the course of disease. PMID- 26285213 TI - Less Frequent and Less Severe Flu-Like Syndrome in Interferon Beta-1a Treated Multiple Sclerosis Patients with at Least One Allele Bearing the G>C Polymorphism at Position -174 of the IL-6 Promoter Gene. AB - One of the most common adverse event of interferon beta (IFNbeta) therapy for multiple sclerosis is flu-like syndrome (FLS), which has been reportedly related to increased levels of cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). Average cytokine levels can be affected by single nucleotide polymorphism in the gene promoter regions. To investigate whether IL-6 -174 G>C and TNF-alpha -376 G>A polymorphisms could be correlated to the incidence of FLS, and whether an anti-inflammatory/antipyretic therapy may influence FLS development, a prospective observational study was performed in 190 treatment naive, multiple sclerosis patients who started IM IFNbeta-1a 30mcg once weekly. The identification of IL-6 -174 G>C and TNF-alpha -376 G>A polymorphisms was achieved by performing an amplification-refractory mutation system. Serum IL 6 levels were measured using enzyme-linked immunosorbent assay in blood samples taken before therapy and then after the first and last IFNbeta-1a injection of the follow-up. FLS-related symptoms were recorded by patients once per week during the first 12 weeks of therapy into a self-reported diary. We found that patients carrying at least one copy of the C allele at position -174 in the promoter of IL-6 gene produced lower levels of IL-6 and were less prone to develop FLS, which was also less severe. On the contrary, the polymorphism of TNF alpha had no effect on FLS. Patients taking the first dose of anti inflammatory/antipyretic therapy in the peri-injection period (within 1 hour) experienced a reduced FLS severity. In conclusion, the study of IL-6 -174 G>C polymorphism would allow the identification of patients lacking the C nucleotide on both alleles who are at risk of a more severe FLS, and may be addressed to a timely and stronger anti-inflammatory/antipyretic therapy for a more effective FLS prevention. PMID- 26285214 TI - Goblet Cell Derived RELM-beta Recruits CD4+ T Cells during Infectious Colitis to Promote Protective Intestinal Epithelial Cell Proliferation. AB - Enterohemorrhagic Escherichia coli and related food and waterborne pathogens pose significant threats to human health. These attaching/effacing microbes infect the apical surface of intestinal epithelial cells (IEC), causing severe diarrheal disease. Colonizing the intestinal luminal surface helps segregate these microbes from most host inflammatory responses. Based on studies using Citrobacter rodentium, a related mouse pathogen, we speculate that hosts rely on immune mediated changes in IEC, including goblet cells to defend against these pathogens. These changes include a CD4+ T cell-dependent increase in IEC proliferation to replace infected IEC, as well as altered production of the goblet cell-derived mucin Muc2. Another goblet cell mediator, REsistin-Like Molecule (RELM)-beta is strongly induced within goblet cells during C. rodentium infection, and was detected in the stool as well as serum. Despite its dramatic induction, RELM-beta's role in host defense is unclear. Thus, wildtype and RELM beta gene deficient mice (Retnlb-/-) were orally infected with C. rodentium. While their C. rodentium burdens were only modestly elevated, infected Retnlb-/- mice suffered increased mortality and mucosal ulceration due to deep pathogen penetration of colonic crypts. Immunostaining for Ki67 and BrDU revealed Retnlb-/ mice were significantly impaired in infection-induced IEC hyper-proliferation. Interestingly, exposure to RELM-beta did not directly increase IEC proliferation, rather RELM-beta acted as a CD4+ T cell chemoattractant. Correspondingly, Retnlb /- mice showed impaired CD4+ T cell recruitment to their infected colons, along with reduced production of interleukin (IL)-22, a multifunctional cytokine that directly increased IEC proliferation. Enema delivery of RELM-beta to Retnlb-/- mice restored CD4+ T cell recruitment, concurrently increasing IL-22 levels and IEC proliferation, while reducing mucosal pathology. These findings demonstrate that RELM-beta and goblet cells play an unexpected, yet critical role in recruiting CD4+ T cells to the colon to protect against an enteric pathogen, in part via the induction of increased IEC proliferation. PMID- 26285215 TI - Assessment of Artificial MiRNA Architectures for Higher Knockdown Efficiencies without the Undesired Effects in Mice. AB - RNAi-based strategies have been used for hypomorphic analyses. However, there are technical challenges to achieve robust, reproducible knockdown effect. Here we examined the artificial microRNA (amiRNA) architectures that could provide higher knockdown efficiencies. Using transient and stable transfection assays in cells, we found that simple amiRNA-expression cassettes, that did not contain a marker gene (-MG), displayed higher amiRNA expression and more efficient knockdown than those that contained a marker gene (+MG). Further, we tested this phenomenon in vivo, by analyzing amiRNA-expressing mice that were produced by the pronuclear injection-based targeted transgenesis (PITT) method. While we observed significant silencing of the target gene (eGFP) in +MG hemizygous mice, obtaining -MG amiRNA expression mice, even hemizygotes, was difficult and the animals died perinatally. We obtained only mosaic mice having both "-MG amiRNA" cells and "amiRNA low-expression" cells but they exhibited growth retardation and cataracts, and they could not transmit the -MG amiRNA allele to the next generation. Furthermore, +MG amiRNA homozygotes could not be obtained. These results suggested that excessive amiRNAs transcribed by -MG expression cassettes cause deleterious effects in mice, and the amiRNA expression level in hemizygous +MG amiRNA mice is near the upper limit, where mice can develop normally. In conclusion, the PITT-(+MG amiRNA) system demonstrated here can generate knockdown mouse models that reliably express highest and tolerable levels of amiRNAs. PMID- 26285217 TI - A Driving Right Leg Circuit (DgRL) for Improved Common Mode Rejection in Bio Potential Acquisition Systems. AB - The paper presents a novel Driving Right Leg (DgRL) circuit designed to mitigate the effect of common mode signals deriving, say, from power line interferences. The DgRL drives the isolated ground of the instrumentation towards a voltage which is fixed with respect to the common mode potential on the subject, therefore minimizing common mode voltage at the input of the front-end. The paper provides an analytical derivation of the common mode rejection performances of DgRL as compared to the usual grounding circuit or Driven Right Leg (DRL) loop. DgRL is integrated in a bio-potential acquisition system to show how it can reduce the common mode signal of more than 70 dB with respect to standard patient grounding. This value is at least 30 dB higher than the reduction achievable with DRL, making DgRL suitable for single-ended front-ends, like those based on active electrodes. EEG signal acquisition is performed to show how the system can successfully cancel power line interference without any need for differential acquisition, signal post-processing or filtering. PMID- 26285219 TI - Optimizing Fingernail Imaging Calibration for 3D Force Magnitude Prediction. AB - This paper discusses the optimization of a fingernail imaging system for predicting fingerpad force. The effects of lighting coloration, calibration grid, and force prediction model on the registration process and force prediction accuracy of fingernail imaging are investigated. White and green LEDs are found to produce statistically similar effects on registration error and force prediction results across all three directions of force. Two calibration grids are implemented, with no statistically significant difference in either registration or force prediction between the Cartesian and cylindrical grid designs. Of the five force prediction models investigated, a principal component regression model based on the pixel intensity eigenvectors estimates the force with the greatest accuracy. This EigenNail Magnitude Model simultaneously estimates force in all three directions with RMS error with 95 percent confidence interval of 0.55 +/- 0.02 N (7.6 percent of the full force range). These results indicate a set of optimal parameter choices for the calibration of a fingernail imaging system. PMID- 26285218 TI - An Inductive Power and Data Telemetry Subsystem With Fast Transient Low Dropout Regulator for Biomedical Implants. AB - This paper presents a capacitorless low-dropout (LDO) regulator with fast transient response and data reverse telemetry circuit for fully implantable wireless transmission applications. We propose a novel hybrid feedback structure using high-frequency compensation technology to achieve a rapid transient response for the LDO regulator. To reduce the size of the implant and transmit neural recordings through the same coil without interfering with power transmission, the load-shift-key (LSK) modulation technique is adopted for back data telemetry. The proposed implantable chip, fabricated using commercial 0.18 MUm complementary metal oxide semiconductor technology, yielded an output power of 15 mW. Under 1.15 V operation voltage, the maximum overshoot and undershoot voltages were less than 45 mV and 55 mV, respectively, for a 15 mA full-load current whose rising and falling time were less than 100 ns. The proposed LSK transceiver uses a digitized demodulator to improve bandwidth efficiency for low carrier frequency operation. PMID- 26285216 TI - Effects of Sevoflurane on Young Male Adult C57BL/6 Mice Spatial Cognition. AB - Inhalation anesthetics are reported to affect cognition in both animals and humans. The influence of inhalation anesthetics in learning and memory are contradictory. We therefore investigated the effects of sevoflurane anesthesia with different durations on cognitive performance and the levels of NMDA receptor subunit NR2B, phosphorylated ERK1/2 (p-ERK1/2) and activated caspase3 in mouse hippocampus. We anaesthetized eight-week old male C57BL/6 mice with 2.5% sevoflurane for durations ranging from one to four hours. Non-anaesthetized mice served as controls. Mice exposed to sevoflurane for one to three hours showed improved performance, whereas mice with exposure up to four hours displayed similar behavioral performance as control group. NR2B was increased both at 24h and at two weeks post sevoflurane exposure in all groups. The p-ERK1/2: total ERK1/2 ratio increased at 24h in all anesthesia groups. The ratio remained elevated at two weeks in groups with two- to four-hour exposure. Activated caspase3 was detected elevated at 24h in groups with two- to four-hour exposure. The elevated trend of activated caspase3 was still detectable at two weeks in groups with three- to four-hour exposure. At two weeks post anesthesia, the typical morphology associated with apoptotic cells was observed in the hippocampus of mice exposed to four hours of sevoflurane. Our results indicate that 2.5% sevoflurane exposure for one to three hours improved spatial cognitive performance in young adult mice. The cognitive improvement might be related to the increase of NR2B, the p-ERK1/2: total ERK1/2 ratio in hippocampus. However, exposure to sevoflurane for four hours caused neurotoxicity due to caspase3 activation and apoptosis. PMID- 26285220 TI - Near Optimal Event-Triggered Control of Nonlinear Discrete-Time Systems Using Neurodynamic Programming. AB - This paper presents an event-triggered near optimal control of uncertain nonlinear discrete-time systems. Event-driven neurodynamic programming (NDP) is utilized to design the control policy. A neural network (NN)-based identifier, with event-based state and input vectors, is utilized to learn the system dynamics. An actor-critic framework is used to learn the cost function and the optimal control input. The NN weights of the identifier, the critic, and the actor NNs are tuned aperiodically once every triggered instant. An adaptive event trigger condition to decide the trigger instants is derived. Thus, a suitable number of events are generated to ensure a desired accuracy of approximation. A near optimal performance is achieved without using value and/or policy iterations. A detailed analysis of nontrivial inter-event times with an explicit formula to show the reduction in computation is also derived. The Lyapunov technique is used in conjunction with the event-trigger condition to guarantee the ultimate boundedness of the closed-loop system. The simulation results are included to verify the performance of the controller. The net result is the development of event-driven NDP. PMID- 26285221 TI - Model-Free Primitive-Based Iterative Learning Control Approach to Trajectory Tracking of MIMO Systems With Experimental Validation. AB - This paper proposes a novel model-free trajectory tracking of multiple-input multiple-output (MIMO) systems by the combination of iterative learning control (ILC) and primitives. The optimal trajectory tracking solution is obtained in terms of previously learned solutions to simple tasks called primitives. The library of primitives that are stored in memory consists of pairs of reference input/controlled output signals. The reference input primitives are optimized in a model-free ILC framework without using knowledge of the controlled process. The guaranteed convergence of the learning scheme is built upon a model-free virtual reference feedback tuning design of the feedback decoupling controller. Each new complex trajectory to be tracked is decomposed into the output primitives regarded as basis functions. The optimal reference input for the control system to track the desired trajectory is next recomposed from the reference input primitives. This is advantageous because the optimal reference input is computed straightforward without the need to learn from repeated executions of the tracking task. In addition, the optimization problem specific to trajectory tracking of square MIMO systems is decomposed in a set of optimization problems assigned to each separate single-input single-output control channel that ensures a convenient model-free decoupling. The new model-free primitive-based ILC approach is capable of planning, reasoning, and learning. A case study dealing with the model-free control tuning for a nonlinear aerodynamic system is included to validate the new approach. The experimental results are given. PMID- 26285222 TI - A Granular Self-Organizing Map for Clustering and Gene Selection in Microarray Data. AB - A new granular self-organizing map (GSOM) is developed by integrating the concept of a fuzzy rough set with the SOM. While training the GSOM, the weights of a winning neuron and the neighborhood neurons are updated through a modified learning procedure. The neighborhood is newly defined using the fuzzy rough sets. The clusters (granules) evolved by the GSOM are presented to a decision table as its decision classes. Based on the decision table, a method of gene selection is developed. The effectiveness of the GSOM is shown in both clustering samples and developing an unsupervised fuzzy rough feature selection (UFRFS) method for gene selection in microarray data. While the superior results of the GSOM, as compared with the related clustering methods, are provided in terms of beta -index, DB index, Dunn-index, and fuzzy rough entropy, the genes selected by the UFRFS are not only better in terms of classification accuracy and a feature evaluation index, but also statistically more significant than the related unsupervised methods. The C-codes of the GSOM and UFRFS are available online at http://avatharamg.webs.com/software-code. PMID- 26285223 TI - Adaptive Neural Network Based Control of Noncanonical Nonlinear Systems. AB - This paper presents a new study on the adaptive neural network-based control of a class of noncanonical nonlinear systems with large parametric uncertainties. Unlike commonly studied canonical form nonlinear systems whose neural network approximation system models have explicit relative degree structures, which can directly be used to derive parameterized controllers for adaptation, noncanonical form nonlinear systems usually do not have explicit relative degrees, and thus their approximation system models are also in noncanonical forms. It is well known that the adaptive control of noncanonical form nonlinear systems involves the parameterization of system dynamics. As demonstrated in this paper, it is also the case for noncanonical neural network approximation system models. Effective control of such systems is an open research problem, especially in the presence of uncertain parameters. This paper shows that it is necessary to reparameterize such neural network system models for adaptive control design, and that such reparameterization can be realized using a relative degree formulation, a concept yet to be studied for general neural network system models. This paper then derives the parameterized controllers that guarantee closed-loop stability and asymptotic output tracking for noncanonical form neural network system models. An illustrative example is presented with the simulation results to demonstrate the control design procedure, and to verify the effectiveness of such a new design method. PMID- 26285224 TI - Sequence Prediction With Sparse Distributed Hyperdimensional Coding Applied to the Analysis of Mobile Phone Use Patterns. AB - Modeling and prediction of temporal sequences is central to many signal processing and machine learning applications. Prediction based on sequence history is typically performed using parametric models, such as fixed-order Markov chains ( n -grams), approximations of high-order Markov processes, such as mixed-order Markov models or mixtures of lagged bigram models, or with other machine learning techniques. This paper presents a method for sequence prediction based on sparse hyperdimensional coding of the sequence structure and describes how higher order temporal structures can be utilized in sparse coding in a balanced manner. The method is purely incremental, allowing real-time online learning and prediction with limited computational resources. Experiments with prediction of mobile phone use patterns, including the prediction of the next launched application, the next GPS location of the user, and the next artist played with the phone media player, reveal that the proposed method is able to capture the relevant variable-order structure from the sequences. In comparison with the n -grams and the mixed-order Markov models, the sparse hyperdimensional predictor clearly outperforms its peers in terms of unweighted average recall and achieves an equal level of weighted average recall as the mixed-order Markov chain but without the batch training of the mixed-order model. PMID- 26285225 TI - Hierarchical Temporal Memory Based on Spin-Neurons and Resistive Memory for Energy-Efficient Brain-Inspired Computing. AB - Hierarchical temporal memory (HTM) tries to mimic the computing in cerebral neocortex. It identifies spatial and temporal patterns in the input for making inferences. This may require a large number of computationally expensive tasks, such as dot product evaluations. Nanodevices that can provide direct mapping for such primitives are of great interest. In this paper, we propose that the computing blocks for HTM can be mapped using low-voltage, magnetometallic spin neurons combined with an emerging resistive crossbar network, which involves a comprehensive design at algorithm, architecture, circuit, and device levels. Simulation results show the possibility of more than 200* lower energy as compared with a 45-nm CMOS ASIC design. PMID- 26285226 TI - Platinum(II)-Based Metallo-Supramolecular Polymer with Controlled Unidirectional Dipoles for Tunable Rectification. AB - A platinum(II)-based, luminescent, metallo-supramolecular polymer (PolyPtL1) having an inherent dipole moment was synthesized via complexation of Pt(II) ions with an asymmetric ligand L1, containing terpyridyl and pyridyl moieties. The synthesized ligand and polymer were well characterized by various NMR techniques, optical spectroscopy, and cyclic voltammetry studies. The morphological study by atomic force microscopy revealed the individual and assembled polymer chains of 1 4 nm height. The polymer was specifically attached on Au-electrodes to produce two types of film (films 1 and 2) in which the polymer chains were aligned with their dipoles in opposite directions. The Au-surface bounded films were characterized by UV-vis, Raman spectroscopy, cyclic voltammetry, and atomic force microscopy study. The quantum mechanical calculation determined the average dipole moment for each monomer unit in PolyPtL1 to be about 5.8 D. The precise surface derivatization permitted effective tuning of the direction dipole moment, as well as the direction of rectification of the resulting polymer-attached molecular diodes. Film 1 was more conductive in positive bias region with an average rectification ratio (RR = I(+4 V)/I(-4 V)) ~ 20, whereas film 2 was more conducting in negative bias with an average rectification ratio (RR = I(-4 V)/I(+4 V)) ~ 18. PMID- 26285227 TI - Validity and Responsiveness of At-Home Touch Screen Assessments in Advanced Parkinson's Disease. AB - The aim of this study was to investigate if a telemetry test battery can be used to measure effects of Parkinson's disease (PD) treatment intervention and disease progression in patients with fluctuations. Sixty-five patients diagnosed with advanced PD were recruited in an open longitudinal 36-month study; 35 treated with levodopa-carbidopa intestinal gel (LCIG) and 30 were candidates for switching from oral PD treatment to LCIG. They utilized a test battery, consisting of self-assessments of symptoms and fine motor tests (tapping and spiral drawings), four times per day in their homes during week-long test periods. The repeated measurements were summarized into an overall test score (OTS) to represent the global condition of the patient during a test period. Clinical assessments included ratings on unified PD rating scale (UPDRS) and 39 item PD questionnaire (PDQ-39) scales. In LCIG-naive patients, the mean OTS compared to baseline was significantly improved from the first test period on LCIG treatment until month 24. In LCIG-nonnaive patients, there were no significant changes in the mean OTS until month 36. The OTS correlated adequately with total UPDRS (rho = 0.59) and total PDQ-39 (0.59). Responsiveness measured as effect size was 0.696 and 0.536 for OTS and UPDRS, respectively. The trends of the test scores were similar to the trends of clinical rating scores but the dropout rate was high. Correlations between OTS and clinical rating scales were adequate indicating that the test battery contains important elements of the information of well-established scales. The responsiveness and reproducibility were better for OTS than for total UPDRS. PMID- 26285228 TI - An Automatic Subject-Adaptable Heartbeat Classifier Based on Multiview Learning. AB - In this paper, a novel subject-adaptable heartbeat classification model is presented, in order to address the significant interperson variations in ECG signals. A multiview learning approach is proposed to automate subject adaptation using a small amount of unlabeled personal data, without requiring manual labeling. The designed subject-customized models consist of two models, namely, general classification model and specific classification model. The general model is trained using similar subjects out of a population dataset, where a pattern matching based algorithm is developed to select the subjects that are "similar" to the particular test subject for model training. In contrast, the specific model is trained mainly on a small amount of high-confidence personal dataset, resulting from multiview-based learning. The learned general model represents the population knowledge, providing an interperson perspective for classification, while the specific model corresponds to the specific knowledge of the subject, offering an intraperson perspective for classification. The two models supplement each other and are combined to achieve improved personalized ECG analysis. The proposed methods have been validated on the MIT-BIH Arrhythmia Database, yielding an average classification accuracy of 99.4% for ventricular ectopic beat class and 98.3% for supraventricular ectopic beat class, which corresponds to a significant improvement over other published results. PMID- 26285229 TI - Representative Vector Machines: A Unified Framework for Classical Classifiers. AB - Classifier design is a fundamental problem in pattern recognition. A variety of pattern classification methods such as the nearest neighbor (NN) classifier, support vector machine (SVM), and sparse representation-based classification (SRC) have been proposed in the literature. These typical and widely used classifiers were originally developed from different theory or application motivations and they are conventionally treated as independent and specific solutions for pattern classification. This paper proposes a novel pattern classification framework, namely, representative vector machines (or RVMs for short). The basic idea of RVMs is to assign the class label of a test example according to its nearest representative vector. The contributions of RVMs are twofold. On one hand, the proposed RVMs establish a unified framework of classical classifiers because NN, SVM, and SRC can be interpreted as the special cases of RVMs with different definitions of representative vectors. Thus, the underlying relationship among a number of classical classifiers is revealed for better understanding of pattern classification. On the other hand, novel and advanced classifiers are inspired in the framework of RVMs. For example, a robust pattern classification method called discriminant vector machine (DVM) is motivated from RVMs. Given a test example, DVM first finds its k -NNs and then performs classification based on the robust M-estimator and manifold regularization. Extensive experimental evaluations on a variety of visual recognition tasks such as face recognition (Yale and face recognition grand challenge databases), object categorization (Caltech-101 dataset), and action recognition (Action Similarity LAbeliNg) demonstrate the advantages of DVM over other classifiers. PMID- 26285230 TI - Constrained Multiobjective Optimization Algorithm Based on Immune System Model. AB - An immune optimization algorithm, based on the model of biological immune system, is proposed to solve multiobjective optimization problems with multimodal nonlinear constraints. First, the initial population is divided into feasible nondominated population and infeasible/dominated population. The feasible nondominated individuals focus on exploring the nondominated front through clone and hypermutation based on a proposed affinity design approach, while the infeasible/dominated individuals are exploited and improved via the simulated binary crossover and polynomial mutation operations. And then, to accelerate the convergence of the proposed algorithm, a transformation technique is applied to the combined population of the above two offspring populations. Finally, a crowded-comparison strategy is used to create the next generation population. In numerical experiments, a series of benchmark constrained multiobjective optimization problems are considered to evaluate the performance of the proposed algorithm and it is also compared to several state-of-art algorithms in terms of the inverted generational distance and hypervolume indicators. The results indicate that the new method achieves competitive performance and even statistically significant better results than previous algorithms do on most of the benchmark suite. PMID- 26285231 TI - Evidence Combination From an Evolutionary Game Theory Perspective. AB - Dempster-Shafer evidence theory is a primary methodology for multisource information fusion because it is good at dealing with uncertain information. This theory provides a Dempster's rule of combination to synthesize multiple evidences from various information sources. However, in some cases, counter-intuitive results may be obtained based on that combination rule. Numerous new or improved methods have been proposed to suppress these counter-intuitive results based on perspectives, such as minimizing the information loss or deviation. Inspired by evolutionary game theory, this paper considers a biological and evolutionary perspective to study the combination of evidences. An evolutionary combination rule (ECR) is proposed to help find the most biologically supported proposition in a multievidence system. Within the proposed ECR, we develop a Jaccard matrix game to formalize the interaction between propositions in evidences, and utilize the replicator dynamics to mimick the evolution of propositions. Experimental results show that the proposed ECR can effectively suppress the counter-intuitive behaviors appeared in typical paradoxes of evidence theory, compared with many existing methods. Properties of the ECR, such as solution's stability and convergence, have been mathematically proved as well. PMID- 26285232 TI - Regularized Primal-Dual Subgradient Method for Distributed Constrained Optimization. AB - In this paper, we study the distributed constrained optimization problem where the objective function is the sum of local convex cost functions of distributed nodes in a network, subject to a global inequality constraint. To solve this problem, we propose a consensus-based distributed regularized primal-dual subgradient method. In contrast to the existing methods, most of which require projecting the estimates onto the constraint set at every iteration, only one projection at the last iteration is needed for our proposed method. We establish the convergence of the method by showing that it achieves an O ( K (-1/4) ) convergence rate for general distributed constrained optimization, where K is the iteration counter. Finally, a numerical example is provided to validate the convergence of the propose method. PMID- 26285237 TI - Move It! PMID- 26285239 TI - Growth and Change at NCCN. PMID- 26285238 TI - Advocating for Older Adults With Cancer: Merging Medicine and Law. PMID- 26285242 TI - On the Verge: Immunotherapy for Colorectal Carcinoma. AB - Although overall survival from colorectal cancer (CRC) has steadily improved over the past decade, there is still work to be done. The gains associated with improved detection and treatment paradigms with chemotherapy and biologics appear to have reached their ceiling. Immune-based therapies have recently demonstrated clinical benefit in other cancers, including CRC with microsatellite instability (MSI), but patients with CRC without MSI have not yet derived benefit. This article reviews the history of CRC immunotherapy trials, the conceptual basis for why the activity of the immune system may be relevant to survival in CRC, and current efforts in CRC immunotherapy, and speculates about future efforts in this area based on experience with immunotherapy efforts in other classes of solid tumors. PMID- 26285240 TI - Cancer Signature Investigation: ERBB2 (HER2)-Activating Mutation and Amplification-Positive Breast Carcinoma Mimicking Lung Primary. AB - Next-generation sequencing of primary and metachronous metastatic cancer lesions may impact patient care. We present a case of relapsed metastatic breast cancer with a dominant pulmonary lesion originally identified as lung adenocarcinoma. A 72-year-old, never-smoker woman with a protracted cough was found to have a large lung mass and regional lymphadenopathy on a chest CT. Lung mass biopsy showed adenocarcinoma with focal TTF-1 (thyroid transcription factor 1) positivity, favoring a lung primary. In addition to stereotactic brain radiation for cerebral metastases, she was started on carboplatin/pemetrexed. As part of the workup, the tumor was analyzed by a 50-gene targeted mutation panel, which detected 3 somatic mutations: ERBB2 (HER2) D769H activating missense mutation, TP53 Y126 inactivating truncating mutation, and SMARCB1 R374Q missense mutation. Of note, the patient had a history of stage IIA triple-negative grade 3 invasive ductal carcinoma of the left breast 1.5 years ago and received neoadjuvant chemotherapy and adjuvant radiation, and underwent a lumpectomy. Further analysis of her primary breast tumor showed a mutational profile identical to that of the lung tumor. Fluorescence in situ hybridization revealed HER2 amplification in the lung tumor, with a HER2/CEP17 ratio of 3.9. The patient was diagnosed with recurrent HER2-positive metastatic breast carcinoma with a coexisting ERBB2 (HER2) activating mutation. Chemotherapy was adjusted to include dual HER2-targeted therapy containing trastuzumab and pertuzumab, resulting in an ongoing partial response. This case demonstrates that a unique genetic mutational profile can clarify whether a tumor represents a metastatic lesion or new malignancy when conventional morphological and immunohistochemical methods are indeterminate, and can directly impact treatment decisions. PMID- 26285243 TI - Importance of Risk Factors for Febrile Neutropenia Among Patients Receiving Chemotherapy Regimens Not Classified as High-Risk in Guidelines for Myeloid Growth Factor Use. AB - BACKGROUND: Clinical practice guidelines recommend prophylaxis in patients with cancer receiving a colony-stimulating factor (CSF) when the risk of febrile neutropenia (FN) is high (>20%). For patients receiving chemotherapy regimens not documented as high-risk, the decision regarding CSF prophylaxis use can be challenging, because some patients may be at high risk based on a combination of the regimen and individual risk factors. METHODS: A retrospective cohort design and US private health care claims data were used. Study subjects received chemotherapy regimens classified as "low" or "intermediate," or unclassified, in terms of FN risk, and were stratified by cancer and regimen. For each subject, the first chemotherapy course, and each cycle and FN episode within the course, were identified. FN incidence proportions were estimated by the presence and number of risk factors and chronic comorbidities. RESULTS: Across the 17 tumor/regimen combinations considered (n=160,304 in total), 74% to 98% of patients had 1 or more risk factor for FN and 41% to 89% had 2 or more. Among patients with 1 or more risk factor, FN incidence ranged from 7.2% to 29.0% across regimens, and the relative risk of FN (vs those without risk factors) ranged from 1.1 (95% CI, 0.8-1.3) to 2.2 (95% CI, 1.5-3.0). FN incidence increased in a graded and monotonic fashion with the number of risk factors and comorbidities. CONCLUSIONS: In this retrospective evaluation of patients with cancer receiving chemotherapy regimens not classified as high-risk for FN in US clinical practice, most patients had 1 or more FN risk factor and many had 2 or more. FN incidence was found to be elevated in these patients, especially those with multiple risk factors. PMID- 26285241 TI - Colorectal Cancer Screening, Version 1.2015. AB - The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colorectal Cancer Screening provide recommendations for selecting individuals for colorectal cancer screening, and for evaluation and follow-up of colon polyps. These NCCN Guidelines Insights summarize major discussion points of the 2015 NCCN Colorectal Cancer Screening panel meeting. Major discussion topics this year were the state of evidence for CT colonography and stool DNA testing, bowel preparation procedures for colonoscopy, and guidelines for patients with a positive family history of colorectal cancer. PMID- 26285244 TI - Treatment Patterns and Outcomes in Patients With Hepatocellular Carcinoma Stratified by Stage-Guided Treatment Categories. AB - PURPOSE: The purpose of this study was to assess the survival and treatment patterns of hepatocellular carcinoma (HCC) stratified by the NCCN stage-guided treatment categories in the absence of a universally accepted staging system for HCC. METHODS: Patients with HCC were identified using ICD-9 codes and inclusion in the Huntsman Cancer Institute tumor registry. Patients were stratified by the NCCN groupings around the time of diagnosis as potentially resectable or operable (RESECT), potentially transplantable (TRANSP), unresectable (UNRESECT), inoperable due to performance status (INOPER), or having metastatic (METAST) disease. Survival and treatment patterns were assessed by NCCN stage-guided treatment categories. RESULTS: A total of 221 patients (72.9% men) with HCC were identified. At the time of diagnosis, patients were categorized as RESECT (n=28, 12.7%), TRANSP (n=33, 14.9%), UNRESECT (n=77, 34.8%), INOPER (n=40, 18.1%), and METAST (n=38, 17.2%). Staging information was not specified for 5 patients (2.3%) even after chart review. Kaplan-Meier analysis demonstrated significant differences in survival between RESECT and UNRESECT categories, and between UNRESECT and METAST categories. The median survivals in RESECT, TRANSP, UNRESECT, INOPER, and METAST categories were 594, 562, 247, 167, and 44 days, respectively. Patients considered RESECT most frequently underwent resection (61%, n=17) and patients considered TRANSP had the highest use of liver transplants (33.3%, n=11). Use of any treatment was low in the METAST (31.6%, n=12) and INOPER (60.0%, n=24) groups. CONCLUSIONS: Treatment patterns in the NCCN groupings correlated with recommended treatment strategies. Overall, the NCCN groupings have a linear relationship in overall survival. PMID- 26285245 TI - Preoperative Distress Predicts Persistent Pain After Breast Cancer Treatment: A Prospective Cohort Study. AB - PURPOSE: Persistent pain after breast cancer treatment (PPBCT) affects 25% to 60% of breast cancer survivors and is recognized as a clinical problem, with 10% to 15% reporting moderate to severe pain several years after treatment. Psychological comorbidity is known to influence pain perception, and evidence links signs of depression and anxiety with development of PPBCT. The purpose of this study was to assess preoperative distress as a predictive factor for development of PPBCT. METHODS: Between October 2008 and October 2009, 426 women diagnosed with primary breast cancer, undergoing surgery at the Department of Breast Surgery, Rigshospitalet, Denmark, were invited to participate in the study. Patients filled out a questionnaire preoperatively, and 4 and 8 months after surgery. Preoperative distress was measured with the Distress Thermometer (DT; 11-point scale, 0-10). We examined the association between severe preoperative distress (using DT >=7) and moderate to severe PPBCT 8 months after diagnosis using a logistic regression model. RESULTS: A total of 357 patients participated in this study and 291 (82%) returned all follow-up questionnaires. Preoperative distress was significantly associated with moderate to severe PPBCT at 8 months, with an adjusted odds ratio (OR) of 2.05 (95% CI, 1.18-3.59; P=.01), and at 4 months, with an OR of 2.23 (95% CI, 1.23-4.05; P=.01). CONCLUSIONS: Preoperative distress was associated with PPCBT, suggesting distress as an independent risk factor for PPBCT. Preoperative identification of patients at risk for PPBCT allows for further research in psychological and pharmacological treatment of this condition. PMID- 26285246 TI - CHAMBER: A Regional Performance Improvement CME Initiative for Breast Cancer Health Care Providers. AB - CHAMBER was a regional educational initiative for providers of care to patients with HER2+ breast cancer. The study goals were to (1) enhance testing for HER2/neu overexpression in patients with invasive breast cancer; (2) increase the appropriate use of targeted therapy for patients with HER2+ breast cancer; and (3) enhance patients' coping ability. This Performance Improvement Continuing Medical Education (PI-CME) initiative included clinical practice assessment, educational activities, and reassessment. Chart review revealed a high rate of HER2 testing (98%) before and after education. Targeted therapy for patients with HER2+ breast cancer declined after the program (from 96% to 61%), perhaps attributable to an increase in awareness of medical reasons to avoid use of targeted therapy. Assessment for patients' emotional coping ability increased after education (from 55% to 76%; P=.01). Rates of testing for HER2 amplification and assessment of emotional well-being after education were consistent with ASCO Quality Oncology Practice Initiative benchmark values. Documentation of actions to address emotional problems remained an area for improvement. PMID- 26285248 TI - Role of Repeat Resection in Non-Muscle-Invasive Bladder Cancer. AB - Repeat transurethral resection (TUR) is indicated for high-grade non-muscle invasive bladder tumors. Repeat TUR is a diagnostic, therapeutic, prognostic, and predictive procedure. Repeat TUR achieves optimal local control by removing residual tumors after initial TUR, improves staging accuracy, provides additional histologic material favoring accurate diagnosis, allocates appropriate therapy with improved outcomes, facilitates response to intravesical therapy, and provides important prognostic information. PMID- 26285249 TI - The Future of Cancer Care: Are We Ready For Personalized Value? PMID- 26285250 TI - Optimizing Endocrine Therapy for Breast Cancer. AB - Endocrine therapy has significantly improved outcomes for patients with early- and advanced-stage hormone-receptor (HR)-positive breast cancer. Despite the success of adjuvant endocrine therapy, some patients with early-stage disease will experience relapse. Additionally, all patients with advanced disease will eventually experience disease progression on endocrine therapy due to resistance. Improved understanding of the mechanisms associated with resistance to endocrine agents has recently led to the approval of new therapeutics. Multiple questions remain unanswered, including the optimal duration of adjuvant therapy, the role of ovarian ablation in early-stage breast cancer in premenopausal women, and how to best incorporate targeted agents with endocrine therapy in the metastatic setting. This article reviews the optimization of endocrine therapy in patients with HR-positive breast cancer, focusing on these controversial areas. PMID- 26285302 TI - Annual salary survey. PMID- 26285303 TI - Special issue in honor of Hans Selye. PMID- 26285247 TI - Cancer-Related Fatigue, Version 2.2015. AB - Cancer-related fatigue is defined as a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning. It is one of the most common side effects in patients with cancer. Fatigue has been shown to be a consequence of active treatment, but it may also persist into posttreatment periods. Furthermore, difficulties in end-of-life care can be compounded by fatigue. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer-Related Fatigue provide guidance on screening for fatigue and recommendations for interventions based on the stage of treatment. Interventions may include education and counseling, general strategies for the management of fatigue, and specific nonpharmacologic and pharmacologic interventions. Fatigue is a frequently underreported complication in patients with cancer and, when reported, is responsible for reduced quality of life. Therefore, routine screening to identify fatigue is an important component in improving the quality of life for patients living with cancer. PMID- 26285304 TI - Abstracts from the Zinqap Annual Scientific Conference, 2012. PMID- 26285305 TI - Abstracts of the Annual Medical Research Day, 2012. PMID- 26285308 TI - Abstracts from the XXII National Congress of the Bulgarian Anatomical Society with International Participation, June 5-6, 2015, Plovdiv, Bulgaria. PMID- 26285307 TI - Abstracts from the Anniversary Scientific Conference 'Science for Health', May 20 22, 2015, Plovdiv, Bulgaria. PMID- 26285309 TI - Proceedings of the 8th International Triticale Symposium, June 10-14, 2014, Ghent, Belgium. PMID- 26285306 TI - Diagnostic interpretation of array data using public databases and internet sources. AB - The range of commercially available array platforms and analysis software packages is expanding and their utility is improving, making reliable detection of copy-number variants (CNVs) relatively straightforward. Reliable interpretation of CNV data, however, is often difficult and requires expertise. With our knowledge of the human genome growing rapidly, applications for array testing continuously broadening, and the resolution of CNV detection increasing, this leads to great complexity in interpreting what can be daunting data. Correct CNV interpretation and optimal use of the genotype information provided by single nucleotide polymorphism probes on an array depends largely on knowledge present in various resources. In addition to the availability of host laboratories' own datasets and national registries, there are several public databases and Internet resources with genotype and phenotype information that can be used for array data interpretation. With so many resources now available, it is important to know which are fit-for-purpose in a diagnostic setting. We summarize the characteristics of the most commonly used Internet databases and resources, and propose a general data interpretation strategy that can be used for comparative hybridization, comparative intensity, and genotype-based array data. PMID- 26285310 TI - The next step Meyer anticipates his new role in AVMA leadership. PMID- 26285311 TI - 47M birds dead in flu outbreak: Egg-laying hens hit hardest, followed by turkeys. PMID- 26285312 TI - Georgia court rejects pet's intrinsic value appeal. PMID- 26285313 TI - Marijuana toxicosis claims yield insights. PMID- 26285314 TI - Some compounding may be allowed, even if still illegal. PMID- 26285316 TI - USDA may require euthanasia of downed veal calves. PMID- 26285315 TI - FDA wants species-level antimicrobial data. PMID- 26285317 TI - A New Revolution? PMID- 26285318 TI - Cardiac Tamponade Associated with Rivaroxaban. AB - Rivaroxaban is an oral anticoagulant approved for prevention of stroke, as well as for the treatment and prevention of venous thromboembolic disease. Hemopericardium is a serious complication of anticoagulant use, which has been reported with oral vitamin-K antagonists and newer oral anticoagulants. At the time of this report, to my knowledge, there are no published reports of hemorrhagic effusion leading to tamponade associated with a Factor Xa Inhibitor. I report a case of hemopericardium with associated tamponade in a patient who developed pericarditis while being treated with Rivaroxaban. The case highlights an important adverse effect of a newer anticoagulant, as well as the particular dangers of medication co-administration in the elderly. PMID- 26285319 TI - Thrombus in Transit through a Patent Foramen Ovale: Surgical Prevention of Impending Stroke. AB - A Transesophageal Echocardiography (TEE) is essential in identifying thrombus in transient in patients with deep venous thrombosis (DVT) presenting with symptoms suggesting potential systemic emboli. We present a case of a 71-year-old gentleman with recent DVT who developed slurred speech and was assumed to have transient ischemia attack (TIA). TEE showed the presence of a large Thrombus in Transit (TIT) through a patent foramen ovale (PFO). Surgical intervention in low to intermediate risk is probably the best option associated with fewer complications of recurrent embolic events than both thrombolysis and anticoagulation. PMID- 26285320 TI - Postmenopausal Bleeding Resulting from Acute Myeloid Leukemia Infiltration of the Endometrium. AB - Postmenopausal bleeding can be the result of numerous etiologies including endometrial carcinoma, vaginal atrophy, and endometrial polyps. Manifestation of a hematologic disease, such as acute myeloid leukemia (AML), is a rare occurrence. A 65-year-old woman with pancytopenia and postmenopausal bleeding was diagnosed with AML. Endometrial biopsy following dilation and curettage of the uterus revealed extensive mononuclear cell infiltrate consistent with AML. The patient was a poor surgical candidate and subsequently underwent treatment with chemotherapy, hormonal therapy, pelvic radiation, and uterine artery embolization to control her vaginal bleeding. A multi-disciplinary approach is necessary for treatment of post-menopausal bleeding resulting from AML infiltration of the endometrium. PMID- 26285321 TI - The Way to a Man's Lungs Is through His Nails: Defining Yellow Nail Syndrome. PMID- 26285322 TI - Weighing in on obesity and breastfeeding: factors possibly related to lower breastfeeding rates in women with higher BMIs. PMID- 26285323 TI - Antenatal information sources for maternal and infant diet. AB - This report describes information sources accessed by pregnant women around antenatal and early infant diet. Australian women in their first pregnancy (n = 277) responded to questionnaires online and on paper between June 2010 and March 2011 as part of the Feeding Queensland Babies Study. Antenatal information sources are reported for maternal diet, breastfeeding and formula-feeding. Pregnant women sought and encountered information for their own and their infants' diet from many sources. Health care professionals provided antenatal dietary information for 80% of respondents and infant feeding advice for 69%. Relatives or friends were the respondents' largest reported information source for infant feeding, reported by 78%. Information on artificial baby milk was accessed on television by 77% and on the internet by 52% of respondents. Health care professionals should proactively support clients' informational needs and address encountered nutrition misinformation. Further research is necessary to establish the nature and accuracy of dietary information in the mass media. PMID- 26285324 TI - Dear health professionals. PMID- 26285325 TI - [The role of the respiratory and relaxation training in the treatment of the patients after the surgical treatment of non-specific pulmonary diseases]. AB - The present study included 62 patients who had undergone the surgical intervention for the treatment of non-specific pulmonary diseases. All the patients were subjected to the psychological and spirometric examination. The study has demonstrated the relationship between the characteristics of the external respiration function on the one hand and the ability to handle stress, the levels of anxiety, tension, emotional instability and hypochondriacal mood on the other hand. It was shown that the respiratory and relaxation training improves the effectiveness of the treatment of the patients presenting with such symptoms due to the correction of their psychological status and optimization of the external respiration function. The highest effectiveness of the respiratory and relaxation training was documented in the patients suffering moderate neurotic disorders. PMID- 26285326 TI - [The importance of muscular disbalance in physical therapy of the patients presenting with pneumonia]. AB - Thematic justification. Pneumonia holds a leading position among the pathological conditions responsible for temporary disability. AIM: The objective of the present study was to develop a rationale for the system of therapeutic physical exercises designed to treat the patients presenting with pneumonia taking into consideration the myofascial disorders and to elucidate its advantages, if any, over the conventional approaches. MATERIAL AND METHODS: A total of 134 patients the patients presenting were examined and treated after they were randomly divided into two groups. The study group was comprised of 73 patients at the mean age of 48.0 +/- 4.0 years while the control group consisted of 61 patients (mean age 48.0 +/- 4.0 years). The standard clinical and laboratory examination and the chest X-ray study of all the patients were supplemented by the evaluation of the external respiration function and the assessment of the state of myofascial structure with the use of the methods for testing the muscular function. RESULTS: The complete resolution of pneumonia documented by X-ray investigations in the patients of the study group was achieved 20.6% more frequently than in controls (p < 0.05). Chest excursion in the study and control groups increased by 36.63% (p < 0.01) and 7.46% (p < 0.05) respectively. The number of the patients with the unaltered vital lung capacity (VLC) (up to more than 90% of the normal value) increased in the study group by 35.6% (p < 0.01). Simultaneously, the number of the patients with moderate and severe disorders decreased in the study group by 21.9% (p < 0.01) and 12.3% (p < 0.05) respectively. The results of the testing of the muscular function suggest that it was most frequently altered in the erector muscle of the spine, gluteus maximus and gluteus medius muscles, musculus quadriceps femoris, iliopsoas muscle, rectus abdominis muscle and oblique abdominal muscle, deep cervical flexor muscles, pectoralis major and pectoralis minor muscles on the side of the affected lung. After the treatment, these changes in the patients of the study group were observed significantly less frequently than in those of the control one. CONCLUSION: The patients with pneumonia developed the signs of muscular disbalance as a result of pathological myofascial disorders in the muscles of the neck, thoracic cage, abdominal wall, paravertebral region, thigh, and the ilio-lumbar region. The program for the combined treatment of the patients presenting with pneumonia based at a hospital facility including the newly proposed method of physical rehabilitation promoted the accelerated resolution of the inflammatory process as is apparent from the results of the X-ray examination. The respiratory exercises prescribed with due regard for the localization of the inflammatory process and specific changes of spirographic measurements together with microcorrection procedures exerted a more pronounced positive influence on the external respiration function and the state of the locomotor system in the patients of the study group in comparison with the control subjects prescribed a complex of conventional therapeutic physical exercises. PMID- 26285327 TI - [The influence of intravenous laser irradiation of the blood on the dynamics of leptin levels and the quality of life of the patients presenting with rheumatoid arthritis]. AB - AIM: The objective of the present study was to estimate the influence of intravenous laser irradiation of the blood on the dynamics of leptin levels and the quality of life of the patients presenting with rheumatoid arthritis. MATERIAL AND METHODS: A total of 132 patients at the age varying from 18 to 65 (mean 52.9 +/- 11.3) years presenting with rheumatoid arthritis (RA) were available for the examination. The diagnosis of RA was based on the results of clinical, laboratory, and instrumental studies in accordance with the criteria of the American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) dated 2010. The patients were divided into two groups. The control group was comprised of the patients who received the traditional medicamental treatment alone (n = 30) while the study group consisted of the patients given a course of intravenous laser irradiation of the blood in addition to the traditional medicamental treatment (n = 102).The course of intravenous laser therapy was performed with the use of a Matrix-VLOK apparatus ("Matrix", Russia) by means of the VLOK + UBI procedure. Each course consisted of 10 sessions per patient without a break for the weekend. RESULTS: The data obtained indicate that the patients with rheumatoid arthritis had the increased plasma leptin level suggesting the development of the inflammatory process. Moreover, the quality of the patients' life was deteriorated. CONCLUSION: The results of this study demonstrate that the combined treatment by means of low-intensity laser irradiation is accompanied by the normalization of the plasma leptin level, suppression of the inflammatory process, and a significant improvement of the quality of life of the patients suffering from rheumatoid arthritis. PMID- 26285328 TI - [The effectiveness of the spa and health resort-based treatment with the application of Essentuki-type drinking mineral waters for the management of non alcoholic fatty liver disease in the patients presenting with type 2 diabetes mellitus]. AB - The objective of the present study was to estimate the effectiveness of the spa and health resort-based treatment of non-alcoholic fatty liver disease in 40 patients at the mean age of 48,8 +/- 5.7 years suffering from type 2 diabetes mellitus. All of them received combined therapy including the application of potable Essentuki-Novaya mineral water (20 patients) or Essentuki No 4 water (20 patients). This therapeutic modality resulted in positive dynamics of clinical symptoms of the disease, the functional liver tests, and parameters of intra hepatic hemodynamics, lipid peroxidation homeostasis, and the hormonal status. It is concluded that the spa and health resort-based treatment with the application of local drinking Essentuki-type mineral waters for the management of non alcoholic fatty liver disease in the patients presenting with type 2 diabetes mellitus leads to the improvement of the main functions of the liver, stabilizes carbohydrate and lipid metabolism, and prevents progression of the pathological process. PMID- 26285329 TI - [The modern methods of the electrical stimulation for the management of neurogenic disturbances of urination]. AB - The results of the present study provide materials for the characteristic and the comparative analysis of the methods for electrical stimulation applied for the treatment of neurogenic disorders of urination and illustrate the up-to-date requirements to this therapy taking into consideration the neuroanatomical and neurophysiological features of micturition. One of the most advanced non pharmacological methods is electrical stimulation and neuromodulation of the urinary bladder function and pelvic floor muscles. The objective of this three step research was to elucidate the mechanisms of action of electrical stimulation and to compare the effects of tibial and pudendal neuromodulation in 22 patients presenting with ischemic lesions in the brain. The first step included the comprehensive clinical and neuroimaging investigations designed to determine the role of functional asymmetry of cortical and subcortical micturition regulatory centers during the recovery process following the ischemic lesions. At the second stage, afferent and central regulation of micturition was investigated by the method of tibial and pudendal somatosensory evoked potentials in the patients presenting with overactive bladder and acute or chronic cerebral ischemia. At the final step, the optimal parameters of neuromodulation were chosen depending on the form of the urination disorder. It is concluded that the study gave evidence of the high therapeutic effectiveness of tibial and pudendal neuromodulation for the treatment of overactive bladder associated with neurological disorders (including ischemic lesions in the brain). PMID- 26285330 TI - [The influence of balneo- and peloid therapy on the characteristics of the hormonal regulation in the women presenting with bacterial vaginosis]. AB - AIM: The objective of the present work was to study the influence of balneo- and peloid therapy on the characteristics of the hormonal regulation in the women presenting with bacterial vaginosis. MATERIAL AND METHODS: The immunoenzymatic assay (ELISA) was used to study characteristics of hormonal regulation in 128 women presenting with bacterial vaginosis and normal prolactin level and 58 women with bacterial vaginosis and concomitant hyperprolactinemia. The study included the evaluation of dynamics of the clinical and laboratory parameters under the influence of peloidtherapy. RESULTS: The application of the sulfide-containing siltypeloids was shown to have positive clinical effect on the adrenal and ovarian function and to exert the modulating action on the levels of the pituitary and sex hormones in women with bacterial vaginosis and normal prolactin levels. In contrast, the same treatment of the women with bacterial vaginosis and hyperprolactinemia causes a further deterioration of hormonal imbalance, increases the initially elevated prolactin level, aggravates disorders in the pituitary and ovarian regulation, and decreases the effectiveness of the treatment. CONCLUSION: The results of the study suggest the necessity of the differential approach to the prescription of balneo- and peloid therapy to the patients with gynecological problems associated with hormonal disorders taking into account the level of prolactinemia. PMID- 26285331 TI - [Investigations into the relationship between respiratory disorders and excessive body weight in the adolescents presenting with bronchial asthma treated based at a specialized health resort facility]. AB - A total of 71 patients with bronchial asthma (BA) were examined and treated based at a specialized health facility of whom 43 ones presented with mild asthma and 26 patients with moderately severe asthma in remission. The median age of the patients was 12,04 +/- 2,08 years. Spirometry parameters: MOS50, MOS75, and PSV, proved to be of high informative value combined with high enough sensitivity and specificity. The significant difference between the groups as a whole (p < 0.05) were documented based on the serum leptin levels that were higher in the overweight patients and especially in the girls (p < 0.05). The leptin level was a similarly sensitive/specific (AUROC > 0.5) and informative (SCDFC > 0.5) parameter which confirms its diagnostic value given it is employed in combination with overweight for the evaluation of the status of the patients suffering from asthma. Negative linear and non-parametric correlation between the functional parameters and the serum leptin levels in the overweight patients with bronchial asthma suggests that the enhanced leptin concentration may serve as a marker of strong obstruction and severe inflammation at all levels of the respiratory tract in the patients presenting with a combination of the two conditions. PMID- 26285332 TI - [Inhalation of Myramistin in the children presenting with acute respiratory diseases]. AB - This paper reports the results of the clinical observations and special investigations carried out with the involvement of the children presenting with acute respiratory diseases treated with the use of a Myramistin solution for inhalation. MATERIAL AND METHODS: The study included a total of 60 children with the above condition at the age varying between 2 and 17 years. Forty patients inhaled the Myramistin solution through a face mask connected to the nebulizer. The remaining 20 children that comprised the control group inhaled Myramistin in the form of a spray. RESULTS: The study has demonstrated the effectiveness of the proposed method that produced beneficial effect on the clinical symptoms of the respiratory diseases and characteristics of peripheral blood. Moreover, it accelerated the recovery of the patients due to the anti-inflammatory and trophic action of the inhaled solution and promoted normalization of mucociliary clearance. The therapeutic effectiveness of the Myramistin spray was significantly lower than that of the solution. CONCLUSION: The results of the study provided a basis for the development of the optimal technologies for the application of the Myramistin inhalation solution to the treatment of the children presenting with acute respiratory diseases of the upper and lower parts of the respiratory tract. PMID- 26285333 TI - [The ultrastructural manifestations of the regenerative processes in the Sertoli cells under the action of low-intensity electromagnetic radiation in the rats subjected to stress]. AB - The experiments on the outbred female rats using the electron microscopic technique have demonstrated that the application of ultrahigh frequency low intensity electromagnetic radiation (LIEMR) with a flux density below 1 mCW/Cm2 and a frequency of approximately 1,000 MHz in the regime of primary prophylaxis and therapeutic-preventive action suppressed the development of the post-stress pathological ultrastructural changes and increased the activity of the regenerative processes in the Sertoli cells. It was shown that the developing adaptive and compensatory changes in the Sertoli cells most frequently involve the energy-producing structures (mitochondria) that undergo the enlargement of their average and total dimensions. Simultaneously, the amount of granular endoplasmic reticulum and the number of ribosomes increased while the intracellular links between the organelles strengthened and the reserve potential of the cells improved. It is concluded that the observed effects may be due to the action of both local and systemic regulation mechanisms. PMID- 26285334 TI - [The enhanced external counterpulsation as a method of non-invasive auxiliary blood circulation used for the combined rehabilitative treatment of the patients surviving after ischemic stroke (a review)]. AB - The present review of the foreign and domestic literature is concerned with the application of the method of enhanced external counterpulsation (EECP) therapy for the treatment of the patients presenting with various diseases. It is shown that many recent publications report extensive investigations of the clinical and neurophysiological aspects of the application of this method for the combined regenerative treatment of the patients surviving after ischemic stroke (IS). The possibility of the influence of EECP therapy on the system of regulation of the cerebral blood flow, the formation of collateral circulation in the ischemic tissue, and the cellular-humoral mechanisms are considered. It is concluded that the introduction of enhanced external counterpulsation therapy into the program of the combined rehabilitative treatment on an individual basis for the patients surviving after ischemic stroke is pathogenetically substantiated as promoting regression of clinical, neurological, and neuropsychological disorders. PMID- 26285335 TI - [The role of evidence-based medicine in the neurorehabilitation: the innovative technologies (a review)]. AB - The present review is focused on the randomized controlled trials and meta analyses in the field of technological means for neurorehabilitation. The available literature data and the results of original observations provide a basis for distinguishing between the following levels of evidence: instrumental verticalization--2a, robot-assisted mechanotherapy--1a, biological feedback--1a, virtual reality--1a, transcranial magnetic stimulation--1a for central hemiparesis and 1b for speech disturbance and unilateral spatial agnosia, transcranial electrical stimulation--2b, electromyostimulation--1a, telerehabilitation--3. It is concluded that the use of the innovative technologies for the purpose of neurorehabiltation is objectively substantiated. Further investigations are needed to allow their application on an individual basis. PMID- 26285336 TI - [The indications for medical rehabilitation of certain oncological patients presenting with the complications of the radical treatment under the conditions of a multi-disciplinary hospital]. AB - This article was designed to help the practitioners by proposing the recommendations for diagnostics and evaluation of the severity of complications of the radical treatment of the patients presenting with breast cancer, stomach cancer, endometrial cancer, cervical cancer, bone sarcoma (osteosarcoma, chondrosarcoma, periosteal sarcoma, et al.). The indications for medical rehabilitation of the patients with these problems are described with special reference to their treatment under the conditions of a multidisciplinary hospital depending on the type and severity of complications of the radical treatment. The results of the long-term investigations and analysis of a large number of observations were used to substantiate the application of the available physiotherapeutic technologies for the medical rehabilitation of the oncological patients belonging to clinical group III. PMID- 26285337 TI - [Annenskie mineral waters: the history of discovery (the 150th anniversary of the balneotherapeutic centre spa "Annenskie waters")]. AB - The present article is an attempt to create a complete picture of the history of foundation of the first Far East balneotherapeutic spa centre known as "Annenskie waters". This article brings together the legends and historical information concerning this locality dated since 1858 up to the present time. The main stages of the development of the medical centre are reviewed starting from the period of unorganized chaotic attendance to the creation of the modern comfortable spa facility, building new bathrooms, halls, dormitories, dining and auxiliary premises. The process of developing and extending indications for the medical application of Annenskie mineral waters is followed backward in the past. The first report on the clinical effectiveness of Annenskie waters is presented. The contribution made by several historical figures to the development of the balneotherapeutic centre is described. PMID- 26285338 TI - Oral Healthcare for Elders: A Missing Link. PMID- 26285339 TI - FOCUS ON: Facial Aesthetics. PMID- 26285340 TI - Claude Berthoin, President and CEO, Denterprise International. PMID- 26285341 TI - I'm Beginning to See the Light. PMID- 26285342 TI - Uncontrolled Dental Caries in a Young Adult: A Therapeutic Perspective and Case Report. PMID- 26285343 TI - Optimal Shaping of Root Canal Systems: Demonstrating the Use of Controlled Memor Ni-Ti Files. PMID- 26285344 TI - Bulimia: Complex Etiology, Challenging Treatment. PMID- 26285345 TI - Nanoceramic CAD/CAM Restorations. PMID- 26285346 TI - A Restorative Challenge: Tetracycline-Stained Teeth. PMID- 26285347 TI - Ensuring Restorative Success With Bruxism Testing. PMID- 26285348 TI - Lasers in Implant Dentistry, Part I. PMID- 26285349 TI - An Oral Bisphosphonate Dilemma. PMID- 26285350 TI - Immediate Implant Prosthesis Via Guided Bone Reduction. PMID- 26285351 TI - Intraoral Repair of Multiple Substrates Using Silication. PMID- 26285352 TI - THALIACEANS, THE NEGLECTED PELAGIC RELATIVES OF ASCIDIANS: A DEVELOPMENTAL AND EVOLUTIONARY ENIGMA. AB - Most developmental biologists equate tunicates to the sessile ascidians, including Ciona intestinalis, and the pelagic appendicularians, in particular Oikopleura dioica. However, there exists a third group of tunicates with a pelagic lifestyle, the thaliaceans, which include salps, pyrosomes, and doliolids. Although thaliaceans have raised the curiosity offamous zoologists since the 18th century, the difficulty of observing and experimentally manipulating them has led to many controversies and speculations about their life cycles and developmental strategies, the phylogenetic relationship within the group and with other tunicates, and the drivers of speciation in these widely distributed animals living in a seemingly uniform environment. Here, we take a historical perspective to summarize 250 years of work on this intriguing group of animals, and explore how modern genomics and imaging approaches are starting to solve fascinating evolutionary and developmental riddles. Recent molecular analyses support previous morphological evidence that ascidians are not monophyletic and that thaliaceans evolved from a sessile ascidian-like ancestor. In parallel, preliminary live-imaging and gene-expression data offer exciting entry points to understand how the adoption of a pelagic lifestyle led to drastic modifications in the morphology, embryology, and life cycle of these tunicates, compared to their sessile ancestor. PMID- 26285353 TI - PROMOTING RESILIENCE. AB - Broadening contingents of ecologists and environmental scientists have recently begun to promote ecological resilience both as a conceptual framework and as a practical goal. As some critics have noted, this growing interest has brought with it a multiplication of notions of ecological resilience. This paper reviews how and why the notion of ecological resilience has been adopted, used, and defended in ecology since its introduction by C. S. Holling in 1973. We highlight the many faces of ecological resilience, but unlike other reviewers who see these as disunified and confused, we interpret ecological resilience as an evolving, multidimensional, theoretical concept unified by its role in guiding practical response to ecological and environmental challenges. This perspective informs a review of some of the factors often recognized as favoring resilience (structural and response diversity, functional redundancy, modularity, and spatial heterogeneity); we show how the roles and relationships of these factors can be clarified by considering them in the theoretical framework of Complex Adaptive Systems (CASs). PMID- 26285355 TI - Social Security Disability Insurance: How Social Workers Can Support Necessary Action. PMID- 26285354 TI - HOW TO STUDY ADAPTATION (AND WHY TO DO IT THAT WAY). AB - Some adaptationist explanations are regarded as maximally solid and others fanciful just-so stories. Just-so stories are explanations based on very little evidence. Lack of evidence leads to circular-sounding reasoning: "this trait was shaped by selection in unseen ancestral populations and this selection must have occurred because the trait is present." Well-supported adaptationist explanations include evidence that is not only abundant but selected from comparative, populational, and optimality perspectives, the three adaptationist subdisciplines. Each subdiscipline obtains its broad relevance in evolutionary biology via assumptions that can only be tested with the methods of the other subdisciplines. However, even in the best-supported explanations, assumptions regarding variation, heritability, and fitness in unseen ancestral populations are always present. These assumptions are accepted given how well they would explain the data if they were true. This means that some degree of "circularity" is present in all evolutionary explanations. Evolutionary explanation corresponds not to a deductive structure, as biologists usually assert, but instead to ones such as abduction or Bayesianism. With these structures in mind, we show the way to a healthier view of "circularity" in evolutionary biology and why integration across the comparative, populational, and optimality approaches is necessary. PMID- 26285356 TI - Suicide Risk, Stress Sensitivity, and Self-Esteem among Young Adults Reporting Auditory Hallucinations. AB - Individuals with subthreshold psychotic experiences are at increased risk for suicidal thoughts and behavior, similar to those with schizophrenia and other psychotic disorders. This may be explained by shared risk factors such as heightened stress sensitivity or low self-esteem. Understanding the nature of this relationship could inform suicide prevention in social work practice. In this study, authors examined the relationship between self-reported auditory hallucinations and suicidal thoughts, plans, and attempts, in a nonclinical sample of young adults, controlling for scores on the Psychological Stress Index and Rosenberg Self-Esteem Scale. Auditory hallucinations were associated with approximately double the odds of suicidal ideation and plans and four times the odds for suicide attempts. This relationship was not explained by stress sensitivity or self-esteem, which were independently related to hallucinations and suicidality, respectively. Subthreshold auditory hallucinations may be a useful indicator of suicide risk. This association may represent a clinically significant relationship that may be addressed through social work interventions intended to alleviate stress sensitivity or improve self-esteem. PMID- 26285357 TI - Modeling Active Aging and Explicit Memory: An Empirical Study. AB - The rapid growth of the population of older adults and their concomitant psychological status and health needs have captured the attention of researchers and health professionals. To help fill the void of literature available to social workers interested in mental health promotion and aging, the authors provide a model for active aging that uses psychosocial variables. Structural equation modeling was used to examine the relationships among the latent variables of the state of explicit memory, the perception of social resources, depression, and the perception of quality of life in a sample of 184 older adults. The results suggest that explicit memory is not a direct indicator of the perception of quality of life, but it could be considered an indirect indicator as it is positively correlated with perception of social resources and negatively correlated with depression. These last two variables influenced the perception of quality of life directly, the former positively and the latter negatively. The main outcome suggests that the perception of social support improves explicit memory and quality of life and reduces depression in active older adults. The findings also suggest that gerontological professionals should design memory training programs, improve available social resources, and offer environments with opportunities to exercise memory. PMID- 26285358 TI - Social Work Assessment Notes: A Comprehensive Outcomes-Based Hospice Documentation System. AB - This article describes the development of an integrated psychosocial patient and caregiver assessment and plan of care for hospice social work documentation. A team of hospice social workers developed the Social Work Assessment Notes as a quality improvement project in collaboration with the information technology department. Using the Social Work Assessment Tool as an organizing framework, this comprehensive hospice social work documentation system is designed to integrate assessment, planning, and outcomes measurement. The system was developed to guide the assessment of patients' and caregivers' needs related to end-of-life psychosocial issues, to facilitate collaborative care plan development, and to measure patient- and family-centered outcomes. Goals established with the patient and the caregiver are documented in the plan of care and become the foundation for patient-centered, strengths-based interventions. Likert scales are used to assign numerical severity levels for identified issues and progress made toward goals and to track the outcome of social work interventions across nine psychosocial constructs. The documentation system was developed for use in an electronic health record but can be used for paper charting. Future plans include automated aggregate outcomes measurement to identify the most effective interventions and best practices in end-of-life care. PMID- 26285359 TI - Addressing Heart Failure Challenges through Illness-Informed Social Work. AB - This article describes the role of social workers in addressing the needs of people with heart failure. Although previous studies have explored the role of social workers in health care settings, few studies have addressed the challenges of specific chronic diseases such as heart failure. To address this gap in the literature, this study used qualitative interviews with health care social workers (n = 8) to obtain in-depth information about activities and challenges related to heart failure care. Findings suggest that health care social workers perceive heart failure as characterized by an uncertain illness trajectory, frequent hospitalizations, and difficulties accessing formal and informal care. These findings suggest the importance of what we term illness-informed social work, a practice that combines heart failure knowledge with social work competencies to address the complex psychosocial issues in heart failure care. PMID- 26285360 TI - Contribution of Positivity Ratio and Self-Control to Reduced Gambling Severity among Adolescents. AB - In the past few years, gambling among adolescents has become a common health risk behavior, one that might lead to other health risk behaviors. Research on the etiology of gambling behavior among adolescents has hitherto focused primarily on the factors contributing to increased gambling severity (GS). The present study is different, in that it examines two key personality components that may help curb GS: self-control (SC) and positivity ratio (PR)--the latter being defined as the positive ratio between positive and negative affects--as factors that predict reduced GS among adolescents. A convenience sample of 595 adolescents, ages 13 to 19 (M = 15.13, SD = 1.53), from six secondary and middle schools in five major cities in Israel, was taken between February and April 2012. Four instruments were used: a Gambling Behavior Scale, the DSM-IV (adapted for juveniles), the Adolescent SC Scale, and the Positive and Negative Affect Schedule. The main findings showed that PR moderated the association between SC and GS--highlighting the importance of PR in reducing the likelihood of problem gambling and bolstering the individual's SC skills and pointing to possible preventive actions that might be taken in the community to promote healthy adolescent behavior. PMID- 26285361 TI - HIV Awareness and Knowledge among Viewers of a Documentary Film about HIV among Racial- or Ethnic-Minority Older Adults. AB - A documentary film on HIV was developed based on social cognitive theory and entertainment educational methods in an effort to increase awareness and encourage protective behavior change related to HIV among older adults. The documentary includes perspectives from racial- or ethnic-minority older adults who are living with HIV and those of health care providers, and was screened in several venues. Authors of this article conducted thematic content analysis of anonymous, written, open-ended responses from 341 film viewers (clinicians and laypeople) who described what they learned about HIV after viewing the film. Four key themes emerged from the analysis: (1) increased awareness about the epidemiology of HIV among older, minority groups and about sexuality among older people; (2) improved general HIV knowledge, including risk reduction strategies and details about HIV testing; (3) awareness of lack of sexual health education among health care providers, and that a call to action is needed; and (4) awareness that HIV reinfection can occur in certain circumstances with people who are already infected. Findings suggest that an educational documentary can be used to effectively increase awareness and knowledge about the impact of HIV among minority older adults, and may also encourage HIV prevention action steps by providers. PMID- 26285362 TI - Health Perceptions and Quality of Life among Low-Income Adults. AB - Marginalized populations may be predisposed to poor health outcomes due to health dis parities. Although much of the research on health and quality of life is from the perspective of the impact of clinical diagnosis, there is a need for more diverse inquiries and recognition of the individuals' perceptions and preferences. The present study examined the importance of an individual's perception of his or her current health in predicting quality of life over and beyond the presence of physical or mental health conditions. The sample included 150 low-income adults, of which 84.7 percent were African American and 15.4 percent were of another minority race or ethnicity. Participants had an average monthly income of $703. Having a better perception of health was significantly associated with increased quality of life scores. Subjective perceptions of current health were a better predictor of quality of life than the presence of a serious physical or mental health condition. The article ends with a discussion of appropriate interventions to improve health perceptions in similar populations predisposed to poor health outcomes. PMID- 26285363 TI - Psychosocial Needs of Relatives of Trauma Patients. AB - In trauma care, the patient is the primary focus of attention. However, patients' relatives also need attention, for two main reasons. First, the support of relatives is an important factor in the convalescence of patients. Second, the trauma means a serious disruption of not only the life of patients, but also that of their relatives. The purpose of this study was to explore the needs of relatives of trauma patients, to what extent these needs are met by the support of social workers, and how relatives benefit from this support. The study was conducted in hospitals in The Netherlands. Needs were measured using the Dutch version of the Critical Care Family Needs Inventory. Results of in-depth interviews were used to develop a questionnaire to explore the type of social worker support and to what extent relatives benefit from this support. Findings show that trauma patients' relatives have a need for information, access to the patient and hospital staff, and psychosocial assistance. In most cases social workers supported relatives and relatives benefited from the support. To ensure that trauma patients' relatives receive the support they need, social workers should be involved in trauma care as the standard of good care. PMID- 26285364 TI - Social Worker Perceptions and Observations Regarding Men's Management of Hemophilia and Use of Community-Based Support. AB - The study reported in this article was conducted in response to Utah service provider concerns that men with hemophilia may be disengaged from their local community-based support network. This study explored the challenges, adaptations, and needs of men with hemophilia from the perspective of Hemophilia Treatment Center (HTC) social workers. Utah's two active HTC social workers participated in face-to-face interviews. Fourteen HTC social workers from surrounding regions completed written interviews. The researcher used a qualitative, grounded theory approach to analyze the data. Resilience theory provided a lens for interpreting the results. Findings from these professionals indicate that men with hemophilia appear to be ambivalent toward services that are available to them for reasons that include work and insurance status, prior personal history with the bleeding disorders community, strength of relationship with local service providers, degree of customization of HTC services, and the desire to maintain personal independence. Understanding this dynamic may be helpful in developing services that are more specifically tailored to the needs of men with hemophilia, in addition to potentially providing stronger community-based support to men with other genetic disorders. PMID- 26285365 TI - Addressing the Needs of Individuals with Autism: Role of Hospital-Based Social Workers in Implementation of a Patient-Centered Care Plan. PMID- 26285366 TI - Pomp and Circumstance and Lifelong Learning. PMID- 26285367 TI - Celebrating Nursing's Past and Future. PMID- 26285368 TI - Failure to Rescue: The Nurse's Impact. AB - Failure to rescue is a major cause of mortality in acute care settings. Several factors contribute to this problem, and nurses hold a significant key to addressing the issue. Using bell curves to analyze patient assessment data enables nurses to recognize indicators of impending crisis and act expediently to safeguard the health of the patient. PMID- 26285369 TI - Improving Quality by Taking Aim at Incontinence-Associated Dermatitis in Hospitalized Adults. AB - A practice-improvement project was launched to implement an evidence-based intervention bundle for incontinence-associated dermatitis (IAD) and evaluate its impact on the identification, prevention, and management of IAD in hospitalized adults. PMID- 26285370 TI - Use of a Novel Teaching Method to Increase Knowledge and Adherence to Isolation Procedures. AB - Adherence to infection prevention precautions is a challenge in many hospitals. The purpose of this study was to determine if an isolation educational program, which included visual demonstrations of cross-contamination during breaks in isolation procedures, increased nursing staff knowledge of and adherence to isolation procedures. PMID- 26285372 TI - A Sergeant's Story. PMID- 26285371 TI - Discharge Time Out: An Innovative Nurse-Driven Protocol for Medication Reconciliation. AB - An innovative method for discharge medication reconciliation was developed by nurses to ensure safe transition of care and improved patient outcomes. The discharge time-out process has empowered nurses to take a more active role in discharging their patients, and has fostered a more collaborative relationship between nurses and physicians. PMID- 26285373 TI - A Salute to the Armed Forces, Veterans, and AMSN Military Members. PMID- 26285374 TI - Nurses Providing Care to Military Veterans in Civilian Hospitals. PMID- 26285375 TI - Becoming a Nurse and Army Officer Through the ROTC Program. PMID- 26285376 TI - Moral Injury is the Wound: PTSD is the Manifestation. PMID- 26285377 TI - Nursing and Health Care in the Veterans Health Administration Today. PMID- 26285378 TI - My Career as a Navy Nurse. PMID- 26285379 TI - A Sailor and a Nurse. PMID- 26285380 TI - Discharging Veterans: Legal and Ethical Issues. PMID- 26285381 TI - Care of the Patient Undergoing Radial Approach Heart Catheterization: Implications for Medical-Surgical Nurses. AB - Primary treatment for coronary vascular disease focuses on therapeutic lifestyle changes. However, additional medical management or even coronary intervention may be required. Access sites for catheterization include the brachial, radial, and femoral arteries. As an increasing number of providers implement transradial cardiac catheterization, education for nurses is a priority. PMID- 26285382 TI - A Review of Antihypertensive Medications, Part I. AB - Hypertension requires careful management, including lifestyle modification and drug therapy. Use of thiazide diuretics and ACE inhibitors is discussed. PMID- 26285383 TI - Pressure Ulcers. PMID- 26285384 TI - Conducting Research with a Team of Clinical Nurses. PMID- 26285385 TI - Fun with Fluids. PMID- 26285386 TI - Physical Examination of the Adult Patient with Chronic Respiratory Disease. PMID- 26285388 TI - PHYSICIANS, VALUE AND COMPOUND INTEREST. PMID- 26285389 TI - DESIGNING THE NEW HEALTH CARE SYSTEM: THE NEED FOR CMO AND CFO COLLABORATION. PMID- 26285387 TI - Clinical Nurse Leader: A Role for the 21st Century. PMID- 26285390 TI - WHAT CONCERNS CMOs IN THE MOVE FROM VOLUME TO VALUE? PMID- 26285391 TI - TRUST: THE KEY TO BUILDING STRONGER PHYSICIAN RELATIONSHIPS. PMID- 26285392 TI - THREE KEYS TO CREATING A CONTINUOUS IMPROVEMENT CULTURE. PMID- 26285393 TI - DIFFICULT OR COMPLEX: CREATING SYSTEMS TO ADDRESS THE NEEDS OF COMPLEX PATIENT CARE. PMID- 26285394 TI - RISKS AND OPPORTUNITIES OF DATA MINING THE ELECTRONIC MEDICAL RECORD. PMID- 26285395 TI - LOST IN TRANSLATION: TRANSITION OF CARE AND POPULATION HEALTH. PMID- 26285396 TI - WHERE IS THE 'AFFORDABLE' IN THE AFFORDABLE CARE ACT? PMID- 26285397 TI - LEADERSHIP AND THE REDISCOVERY OF FIRE. PMID- 26285398 TI - THE INFECTIOUS DISEASE SERVICE LINE: NEXT FRONTIER IN HOSPITAL/PHYSICIAN CO MANAGEMENT? PMID- 26285399 TI - A LOOK AT PHYSICIAN COMPENSATION MODELS. PMID- 26285400 TI - DOES MANAGERIAL SCIENCE HOLD THE KEY TO MANAGING THE UNCOOPERATIVE PATIENT? PMID- 26285401 TI - RE-ENTRY: WHAT EVERY PHYSICIAN LEADER SHOULD KNOW. PMID- 26285402 TI - Stepping back to look forward. PMID- 26285403 TI - The accreditation of nursing education in Australia. AB - This paper aims to explore and discuss the role that ANMAC and the accreditation standards play in pre-registration nursing education nationally. The context of the discussion is situated in the continuum of events that mark the accreditation of nursing education in Australia. The National Registration and Accreditation Scheme has given rise to significant challenges related to the accreditation of nursing programs of education in Australia. Given the importance of accreditation to the quality of nursing education, ANMAC in its appointed role as accrediting authority, must fill the position rather than occupy it. Enhancing transparency and effectiveness is central to ensuring accreditation facilitates quality in nursing education. Given ANMAC's key position, further work is needed in developing a broad base of expertise by fostering scholarly output in the substantive area of nursing accreditation. There is a concerning lack of research centred on the accreditation of programs of nursing education along with the processes associated with it. This problem is not restricted to the Australian context but also extends internationally. In this context, the expertise of accreditors ought to be questioned along with the processes ANMAC use to identify individual capability. As such, the selection of experts needs to be articulated clearly by ANMAC along with the ownership of introducing a research culture into accreditation. PMID- 26285405 TI - Nursing and climate change: An emerging connection. AB - Awareness of the importance of climate change to public health has been growing. Calls for health professionals, including nurses, to take action to prepare for, and mitigate, climate change have been coming from a number of credible sources. This paper will assist nurses to recognise the health consequences of climate change, to generate and disseminate knowledge about these health consequences, to be active in mitigating emissions locally and within their organisations and to advocate and have input into policy processes. It is valuable for nurses to understand the health co-benefits of emission mitigation and the current health costs of fossil fuels. As advocates for evidence-based public health initiatives, nurses have a role to play in communicating to the public and to policy makers accurate information, including about the health costs of fossil fuel policies and the affordability of renewable energy technologies. PMID- 26285404 TI - Characteristics of the nurse manager's recognition behavior and its relation to sense of coherence of staff nurses in Japan. AB - The recognition behaviors strongly influence the job satisfaction of staff nurses and an extremely important factor for the prevention of burnout and the promotion of retention. Additionally, among internal factors that may affect worker's mental health, a sense of coherence (SOC) is an important concept from the view of the salutogenic theory and stress recognition style. Individual's SOC increases in relation to recognition behavior. However, in Japan, few studies have examined the effect of recognition behaviors on the SOC of staff nurses. The purpose of this study was to investigate how staff nurses perceive recognition behaviors of the nurse manager and to determine the relationship between recognition behaviors and the staff nurses' SOC. This quantitative, cross sectional study involved 10 hospitals in Japan. A total of 1425 nurses completed the questionnaire. As a result, the perceptions of nurse manager's recognition behaviors by staff nurses were evaluated by presentation and report, individual value and the transfer of responsibility, and professional development. The median score of staff nurse SOC-13 was 50 (IQR; 45-55). Significant differences in SOC scores were found in marital status, age, years of experience, and mental and physical health condition. In conclusion, recognition behaviors by the nurse manager can improve staff nurse's SOC and effectively support the mental health of the staff nurse. PMID- 26285406 TI - Competency assessment tools: An exploration of the pedagogical issues facing competency assessment for nurses in the clinical environment. AB - Competency assessment is a paradigm that is common in the healthcare environment and this being particularly true within the nursing profession. Demonstration of competence is necessary to meet the requirements of healthcare organisations and is a mandated requirement of nurses by the Nursing and Midwifery Board of Australia. Within the nursing education sector, one approach to determine competence, is through the use of competency assessment tools. Despite widespread use of competency assessment tools there remains ongoing concerns relating to the efficacy of competency assessment tools as a mean to demonstrate 'competency' amongst enrolled and registered nurses in the clinical environment. The authors of this paper ascertain that competency assessment tools run a serious risk of being nothing more than a 'quick-fix' means of assessment to demonstrate 'nursing competence' required for key performance indicators and clinical governance and that will provide evidence for accreditation standards. Based on this premise, the authors, provide an alternative approach to the use of competency assessment tools that moves away from a 'tick-box' approach to a 'patient-centred' competency model. This approach increases the reliability and validity of competency assessments, allows for the recognition of the knowledge, skills and experience of individual nurses, offers a more satisfying and rewarding approach to demonstrating 'competency' for nurses and finally, demonstrates 'real-life' competency. PMID- 26285407 TI - Australian survey of current practice and guideline use in adult cancer pain assessment and management: The community nurse perspective. AB - BACKGROUND: Cancer pain remains a major public health concern. Despite effective treatments being available to manage the majority of cancer pain, this debilitating symptom is frequently under treated. As cancer has becomes a chronic disease a range of health professionals, including community nurses in Australia are increasingly caring for people living with cancer related pain. Yet, little is known about community nurses capacity to assess and manage cancer pain in accordance with best available evidence. OBJECTIVES: This study aimed to: identify the barriers and facilitators to adult cancer pain assessment and management as perceived by Australian health professionals; identify if cancer pain guidelines are currently used; identify barriers and facilitators to guideline use; and establish the need for Australian cancer pain guidelines. This article reports on community nurses' perceptions of managing cancer pain in the community setting. METHODS: A cross-sectional survey was administered online. Invitations were circulated via peak bodies and clinical leaders seeking the views and experiences of health professionals involved in caring for people living with cancer pain. Descriptive statistics were used to summarise the quantitative data, and thematic content analysis were used to describe the qualitative data. RESULTS: Sixty-two community nurses responded to the survey, representing 29% of the total sample. These participants reported high levels of adherence to accepted cancer pain management practices in their workplace, with 71% nominating the Palliative Care Therapeutic Guideline V.3 as being most frequently used to manage community patients' cancer related pain. Key barriers to effective cancer pain management in the community were: difficulties accessing non-pharmacological interventions (89%), lack of coordination by multiple providers (89%), and impact of distance on ability to access pain-related services for patients (86%). CONCLUSION: A range of system, health professional and consumer barriers limit access to best available treatment in the community setting for people with cancer pain. A clinical pathway that gives step-by-step guidance on evidence-based practice along with an evaluation framework may be the best way of enabling community nurses to ensure their patients with cancer related pain have access to best available care. PMID- 26285408 TI - As they see it: A qualitative study of how older residents in nursing homes perceive their care needs. AB - OBJECTIVES: Meeting care needs of nursing home residents is a significant element in providing the best quality care. A literature review revealed that there is poor understanding of the care needs of older residents from their own viewpoints within a nursing home context. Therefore, this study aimed to explore the older nursing home residents' care needs from their own perspectives. METHODS: This was a qualitative study. In-depth interviews were conducted by a purposive sample of 18 nursing home residents with a mean age of 80.7 years in Taiwan. All data was transcribed and coded for emerging themes. RESULTS: A qualitative data analysis generated six themes including the body, economics, environment, mind, preparation for death, and social support, referred to subsequently as BEEMPS. CONCLUSIONS: These findings can provide nursing home managers with information on how to improve nursing home care protocols to accommodate residents' expressed needs and also inform healthcare professionals about the care needs of older residents, thus fostering better care. PMID- 26285409 TI - Direct care activities for assistants in nursing in inpatient mental health settings in Australia: A modified Delphi study. AB - This paper describes a modified Delphi approach to developing a set of direct care activities for assistants in nursing (AIN) working in mental health settings within a metropolitan local health district (LHD). Although AIN have been employed in a range of health care settings in recent years, they have not routinely been placed in the mental health context. A modified Delphi method was utilised as it has a proven history of application in the health sector, particularly in circumstances where new guidelines, policies or practice frameworks were required. A set of direct care activities for working in mental health settings was developed from an initial set of baseline descriptors and then two rounds of consensus conferencing with a panel of experts. This paper will detail that process and discuss the resulting implications for the consensus reached on the set of direct care activities. PMID- 26285410 TI - Moments of speaking and silencing: Nurses share their experiences of manual handling in healthcare. AB - Nursing care involves complex patient handling tasks, resulting in high musculoskeletal injury rates. Epidemiological studies from the 1980s estimated a lifetime prevalence of lower back injuries for nurses between 35 and 80%. National and international studies continue to mirror these findings. Despite the development of programs intended to reduce manual handling injuries, sustainable solutions remain elusive. This paper reports on a study of nurses speaking about their perspectives on current manual handling practices. Qualitative research conducted in 2012 investigated nurses' perceptions and experiences relating to manual handling in the healthcare context and their participation in injury prevention programs. There were two research methods: semi-structured interviews and researcher reflective journaling. The research was framed in critical emancipatory methodology. Thirteen nurses from two Australian states participated in the study. Thematic analysis revealed an overarching theme of 'power relations' with a subcategory of '(mis)power' that comprised two subthemes, these being 'how to practice' and 'voicing practice issues'. Specifically, this paper explores nurses verbalising their views in the workplace and responses which left them feeling silenced, punished and disillusioned. The findings suggest that the sociopolitical context within which nurses practice impacts upon their ability to voice concerns or ideas related to manual handling. Inclusion of nurses in the manual handling dialogue may generate an expanded understanding of, and the potential to transform, manual handling practices in healthcare environments. PMID- 26285411 TI - An analysis of Australian graduate critical care nurse education. AB - BACKGROUND: Preparation of specialist critical care nurses in Australia is at graduate level, although there remains considerable variation in courses offered in relation to qualification, content, assessment and outcomes. As higher education providers must now comply with the Australian Qualifications Framework (AQF) a study was conducted to examine existing critical care courses and graduate practice outcomes. METHODS: Twenty-two critical care courses were reviewed. Data sources included course provider, websites, course curricula and telephone interviews with course coordinators. A framework approach, was used consisting of five key stages: preliminary immersion of raw data, conceptualising a thematic framework, indexing, charting, mapping and interpretation of data. FINDINGS: Analysis revealed considerable variations in course delivery and graduate practice outcomes. Most courses used professional competency standards as a framework for course curricula and clinical assessment, with inconsistency in their translation to graduate practice outcomes. Twenty-one courses included clinical assessment at graduate certificate level with no clinical assessment conducted at master level. The expected practice outcome for fifteen courses was safe practice with graduates not expected to practice at a specialist or team leadership level. Minimum graduate practice standards were not included in three courses as an expected outcome. CONCLUSION: The AQF requires graduate nurse education to be compliant with academic outcome standards. The findings of our study indicate variations between courses and subsequent graduate practice outcomes. It is therefore timely to establish national critical care education graduate practice standards. PMID- 26285412 TI - A multi-perspective focus-group approach to revise items in a dietary self efficacy scale for older Taiwanese adults. AB - AIM: To revise items in the Cardiac Diet Self-Efficacy Scale, Chinese version (CDSE-C) using focus groups. BACKGROUND: There is limited literature on using focus groups with older adults as well as nursing and nutrition professionals to revise a questionnaire. METHODS: A qualitative research with multi-perspective focus-group approach was used from February through June 2009. Four serial focus groups were conducted including two focus groups of older adults from Taipei County (n = 6) and Yilan County (n = 6), one group of 5 nursing professionals, and one group of 4 nutritionists. RESULTS: Serial focus group discussions added one category to the CDSE-C (reducing salt) and 3 items, resulting in an 18-item scale with six categories: healthy eating behaviors, reducing fat and cholesterol, resisting relapse, increasing fiber and vegetable, reducing sugar, and reducing salt. CONCLUSIONS: This revised measure can serve as a reliable tool for assessing older Chinese adults' healthy eating self-efficacy to evaluate and improve nutritional status in this population. PMID- 26285413 TI - Effect of end-of-life care education using humanistic approach in Korea. AB - The essential concept of hospice and palliative care nursing is a humanistic approach to patient care. The purpose of this study was to examine the effects of a humanistic end-of-life care course on South Korean undergraduate nursing students' attitudes toward death, death anxiety, and communication skills. A nonequivalent control group design was used. Thirty-nine students from two universities were allocated to the control (n = 20) and experimental (n = 19) groups. Participants in the experimental group were enrolled in an end-of-life care course that utilized humanistic approach two hours per week for 16 weeks. The data were analyzed using the SPSS WIN 17.0. Attitudes toward death and communication skills in the experimental group were found to have increased compared with those of the control group. In conclusion, the humanistic end-of life care course is effective in reducing negative attitudes toward death and increasing the communication skills of Korean nursing students. PMID- 26285414 TI - Literature review: An exploration of the role of the Australian breast care nurse in the provision of information and supportive care. AB - Breast care nurses (BCNs) were introduced to the Australian health care system in the 1990s to facilitate better continuity of care and increase psychosocial support to women with breast cancer. Yet women with breast cancer, particularly those in rural and remote Australia have high levels of unmet supportive needs. The purpose of this literature review was to examine the role of the Australian breast care nurse in the provision of information and support to women with breast cancer. A literature review was conducted using a number of databases from January 2006 to November 2012. Pre-set criteria were used, and nine research papers were identified; one randomised control trial, five quantitative studies, two qualitative studies and one mixed method study. Of the nine studies identified, only one attempted to explore the national perspective, however participants from Tasmania were not used. Overall, the review revealed very few published Australian studies evaluating the role of the BCN since 2006. The results demonstrate a need for larger studies conducted on a national scale, using participants from diverse geographical areas to gain more insight into the level of access to BCN care experienced by Australian women from both urban and rural and remote areas. It is recommended that further research be undertaken in order to build up a body of quantitative data about the role of the Australian BCN in providing information and support to women. PMID- 26285415 TI - The Perioperative Nurse Surgeon's Assistant: Issues and challenges associated with this emerging advanced practice nursing role in Australia. AB - AIMS: The aim of this study was to obtain Perioperative Nurse Surgeon's Assistants' views about their emerging new role in contemporary nursing practice in Australia. BACKGROUND: Internationally advanced practice nursing has led to a range of specialist roles aimed at delivering higher quality, efficient nursing care. In 2005 an Australian university developed the Perioperative Nurse Surgeon's Assistant graduate education and training program to provide nurses with an opportunity to gain advanced practice knowledge and extended skills specifically in the perioperative setting. DESIGN: This study was a qualitative research design that used online surveys and in-depth interviews to explore the issues and challenges associated with the introduction of the (currently non accredited) Perioperative Nurse Surgeon's Assistant role in Australia. METHODS: Experienced Australia perioperative nurses who had undertaken graduate education and training in this field were recruited for this study. Data were collected between August and October 2011. An inductive thematic analysis was used to interpret the findings. RESULTS: Eighteen nurses completed the online survey and six were interviewed (n = 24). Nurses cited their commitment to professional development and the delivery of high quality patient care, along with surgeons' encouragement for them to complete specialist clinical training, as key reasons for undertaking Perioperative Nurse Surgeon's Assistant education and training. CONCLUSIONS: The Perioperative Nurse Surgeon's Assistant role led to greater job satisfaction and autonomy, and assisted nurses to better meet the needs of patients, surgeons and clinical perioperative teams. Without formal recognition of the Perioperative Nurse Surgeon's Assistant role its future in the Australian health care system is under threat. PMID- 26285416 TI - Experiences of Turkish undergraduate nursing students in the intensive care unit. AB - BACKGROUND: Clinical practicum provides many opportunities for nursing students to learn more about their subject and develop essential nursing skills. In contrast, nursing students often have difficulties during their clinical practicum. AIM: This study aims to describe the clinical experiences of undergraduate nursing students in the intensive care unit. METHODS: A descriptive qualitative approach was used in this study. The study was performed at a military medical academy between 1 March and 30 April 2008. The study was conducted with 15 fourth-year baccalaureate nursing students. Data were obtained through open-ended and in-depth audio-taped interviews, which lasted approximately 35-45 min. FINDINGS: Themes emerged from the participants' descriptions of their experiences in the intensive care unit: anxiety, fear of doing harm, emotional connection and empathy, improving self-confidence, perceived responsibility for patients, prioritizing care of patients, preserving dignity, coping with confronting situations, and communication in the intensive care unit. CONCLUSION: The views and expectations of nursing students regarding intensive care practice are important for the organization of the nursing education environment. The nursing curriculum must be revised and developed according to the needs of students. PMID- 26285417 TI - Satisfaction with clinical placement--The perspective of nursing students from multiple universities. AB - Projected nursing shortfalls in Australia have identified the need for organisational planning and strategies around recruitment and retention in healthcare facilities. Strategies include but are not limited to alliances with university faculty and the quality of undergraduate clinical placement experience. This cross-sectional study explored undergraduate nursing students' satisfaction with clinical placement experience from the perspective of multiple university faculties, and the relationship this has with future employment intention at a metropolitan hospital in Sydney, New South Wales. Findings from respondents demonstrated satisfaction with the clinical placement on the following criteria: expectations being met; welcoming of unit staff and attitudes of thereafter; clinical and university facilitator support; and participation in patient care. Three quarters of respondents also indicated that they would consider the hospital as a future employer. Satisfaction with clinical placement experience may aid organisational recruitment strategies. PMID- 26285418 TI - Vivian Bullwinkel: A model of resilience and a symbol of strength. AB - BACKGROUND: The story of one of Australia's most well-known women in history, Vivian Bullwinkel, is a symbol of strength for nursing. She and her companions who were prisoners of war during World War II, refused the position of victim and went on to contribute much to the world after their ordeal. DISCUSSION: These women embody important elements of resilience that it is our duty to convey to generations of nurses so that they may be inspired to rise above adversity, foster connection with like-minded others, use adaptive coping mechanisms and soft power, be gentle yet persistent in their resistance practices, and most of all to do good work throughout their nursing careers. This paper argues that oppression theory provides only a limited understanding of present woes affecting nursing. Resilience theory suggests future actions and is therefore further enlightening. By examining the experiences of Bullwinkel, students can be assisted to see that stress has been a constant theme across nursing history. However ways of rising above adversity can be illuminated by critically and deeply examining aspects of iconic leaders and heroic stories such as can be found in the life of Vivian Bullwinkel. Summary: Students who are offered the chance to examine this symbol of strength in our profession may decide to internalise some of the positive traits and resolve to use the behaviours she and her contemporaries used to help them create for themselves a fulfilling career, pride in their profession and strong sense of purpose. PMID- 26285419 TI - Coordinating end of life care for individuals with a mental illness--A nurse practitioner collaboration. AB - People with a severe and persistent mental illness (SPMI) who develop a life limiting illness are one of the most vulnerable and marginalised groups of people in society today (Woods, Willison, Kington, & Gavin, 2008). In addition to the effects of mental illness, individuals who also have comorbid life limiting illness frequently suffer the compounding issues of social isolation, declining physical abilities and physical pain. The Integrated Mental Health and Palliative Care Task (IMhPaCT) was an eighteen-month project funded through an Australian Government Department of Health and Ageing Grant. The project included a range of service improvement initiatives to enhance the quality of care for individuals with SPMI who also had a life limiting illness. This paper will report on the collaboration between two nurse practitioners, from the specialities of Mental Health and Palliative Care and their impact on optimising end of life care for this client group. Both specialities are underpinned by similar values including addressing the needs of the whole person and the importance of developing a therapeutic relationship (McGrath & Holewa, 2004). This paper will demonstrate how similarities in philosophy, as well as differences in focus of care, enhanced joint clinical practice at an advanced and extended level. PMID- 26285420 TI - "Lack of mental health support ruins lives". PMID- 26285421 TI - Safe staffing app to revamp rotas. PMID- 26285422 TI - UKIP pledges to restore state-enrolled 'home-grown' nurses. PMID- 26285423 TI - One-third of NHS staff 'not secure' to whistleblow. PMID- 26285424 TI - Barts appoints eminent interim chief nurse. PMID- 26285425 TI - Mental health student nurses urged to challenge convention. PMID- 26285426 TI - 'You need us,' carers tell mental health nurses. PMID- 26285427 TI - NICE issues new guidelines on safe staffing levels for midwives. PMID- 26285428 TI - Royal College of Midwives votes to accept 1% pay settlement. PMID- 26285429 TI - 'No evidence of national nurse shortage' claim. PMID- 26285430 TI - Pocket mirrors issued to reduce pressure ulcers. PMID- 26285431 TI - Worcestershire to launch inquiry into handling of nurse "bullying". PMID- 26285432 TI - Colchester trust struggling with high vacancies. PMID- 26285433 TI - "FGM must now be reported but reinfibulation guidance is needed" . PMID- 26285434 TI - "Bridging the age gap could help to solve the staffing crisis". PMID- 26285435 TI - Using information prescriptions in diabetes. AB - Information prescriptions are designed to give people with diabetes the information they need to understand, engage with and improve on their health targets. The prescriptions are short, personal, easy to read and clinically accurate, and are designed to support care planning and behaviour change. PMID- 26285436 TI - Type 2 diabetes: prevention, diagnosis and management. PMID- 26285437 TI - Managing diabetes in people with dementia. AB - Diabetes and dementia may manifest simultaneously: one is potentially life threatening, the other causes severe, progressive loss of memory and cognitive function. Where they coexist, they present nurses with challenges such as administering life-saving interventions to patients who are unable to give informed consent. This article offers guidance on the clinical and ethical challenges involved in blood glucose monitoring and medicines administration in patients with dementia. PMID- 26285438 TI - Encouraging student feedback on placements. AB - Student nurses at Guy's and St Thomas' Foundation Trust participated in pilot work for the local education and training board to ensure clinical placements were fit for purpose. This article looks at how they recognised a good practice placement and which themes emerged to highlight what they felt led to an effective learning environment. Feeling valued and being able to raise concerns in a transparent, open culture was important to them. The trust is working to ensure students can raise concerns in a supportive environment. PMID- 26285440 TI - 60 seconds with Gabriel Ngalomba. PMID- 26285439 TI - Interventions to tackle substance use in schools. PMID- 26285441 TI - Staying focused on patients. PMID- 26285442 TI - [Conventional medicine, evidence-based medicine, personalized medicine: three complementary approaches]. PMID- 26285443 TI - [THE FOUNDATIONS OF EVIDENCE-BASED MEDICINE]. AB - The fundamentals of Evidence-Based Medicine (EBM) are the clinical experience, the application of best evidences from research and the consideration of patient expectations. It enabled significant progresses in the management of diseases with a low or multifactorial causality. But it has also led to unintended negative consequences, partly related to conflicts of interest. The objective of this article is to bring the attention back to the scientific rigor that must sustain the medical practice, namely in the occurrence : 1) formulating a question that addresses all the elements of an individual clinical situation; 2) exploring the literature systematically; 3) estimating the degree of confidence in the conclusions of clinical trials. EBM provides intuitive tools to address some uncomfortable concepts of biostatistics and to identify the biases and the embellished data that invalidate many studies. However, it is difficult to decide of the care of a single patient from observations issued from the comparison of'heterogeneous groups. Personalized medicine should help to overcome this difficulty and should facilitate clinical decision making by targeting the patients who are most likely to benefit from an intervention without much inconvenience. PMID- 26285444 TI - [STRENGTHS AND WEAKNESSES OF RANDOMISED CLINICAL TRIALS: EVOLVING CHANGES ACCORDING TO PERSONALIZED MEDICINE]. AB - Randomised Controlled Trials (RCTs) represent the cornerstone of Evidence-Based Medicine (EBM). Based upon the rules of Good Clinical Practice (GCP), they offer many strengths but also present some weaknesses. The rigorous methodology used allows avoid bias related to confounding factors (through a control group), selection bias (through randomisation) and interpretation bias (through double blinding). However, patients recruited in clinical trials and study experimental conditions markedly differ from the situation in real life. Furthermore, clinical trials recruit a mix of good and poor responders, so that the average therapeutic response is most often mitigated. Clinical trials must evolve according to the new concepts of personalized medicine to become even more performing. In a near future, they must progress from a statistical analysis on large cohorts of patients to a more individualized analysis guided by patient phenotype and genotype characteristics. PMID- 26285445 TI - [PHARMACEUTICAL INDUSTRY AND PERSONALIZED MEDICINE: A PARADIGM SHIFT IN THE DEVELOPMENT OF NEW DRUGS]. AB - The cost of pharmacotherapy is increasing in the health care budget. The pharmaceutical industry is facing the exhaustion of medications that are largely prescribed and have a high profitability (blockbusters). Because of patient heterogeneity, there is a great interindividual variability of the responses to drug therapy. Thus, it is essential to better detect potential <> to avoid waste of resources resulting from the prescription of expensive drugs to poor responders. The development of personalized medicine, or precision medicine, certainly offers opportunities to the pharmaceutical industry, but also exposes it to new big challenges. PMID- 26285446 TI - [PERSONALIZED MEDICINE: NEW CHALLENGES FOR THE PHYSICIAN]. AB - The clinician has to cope with new advances in medicine. Traditional medicine, which is based upon pathophysiological reasoning and clinical experience, has been reinforced by evidence-based medicine, which relies on levels of evidence provided by controlled clinical trials carried out on cohorts of patients. Since a few years, personalized medicine has been put at the forefront. A therapy tailored to every patient, if possible characterized by biomarkers, among which, since the achievement of the whole human genome sequencing, an increasing number of genetic markers. Personalized medicine should be used as a complement of traditional and evidence-based medicine. Physicians should progressively integrate this new strategy in their therapeutic approach. Hence, clinicians have to face new challenges as far as scientific knowledge, practical applications and physician-patient relationship are concerned. PMID- 26285447 TI - [PERSONALIZED MEDICINE: ALL BENEFITS FOR THE PATIENT BUT NEW CHALLENGE IN THE PHYSICIAN-PATIENT RELATIONSHIP]. AB - Personalized medicine should lead to major advances for patient care since it contributes to deliver the <>. In curative medicine, this approach should improve the efficacy of medications by initial selection of "good responders", and should reduce adverse events due to poor tolerance or toxicity by a better pharmacological choice and a more appropriate individualized dose adjustment. Over recent years, considerable technical advances have increasingly linked personalized medicine with predictive and preventive medicine. This progress raises hopes for major advancements in medicine, but may also cause some concern among the lay public. The patient should actively be involved in the decisions related to his/her health, in a true model of participatory medicine. Finally, personalized medicine should leave its strict technical nature and become more interested in the person as a whole, within a holistic approach also integrating psychosocial aspects that are so important in the physician-patient relationship. PMID- 26285448 TI - [PHARMACOGENOMICS AND PERSONALIZED MEDICINE: TOWARDS A SYSTEMATIC GENOMIC SCREENING?]. AB - Recent advances in medical genomics open new perspectives for personalized medicine through the identification of genetic variants that influence drug response and/or the risk of side effects. Today, the clinical applications of pharmacogenetics remain scarce as a consequence of the cost and turn-around-time of genetic tests. However, a few tests are recommended, for instance before the prescription of some anti-cancer agents or the anti-retroviral agent abacavir. In the future, we will probably move either towards rapid targeted tests or towards a large screening, before any diagnosis, of all the genetic factors influencing the therapeutic response. In that case, physicians will have to consult the patient genomic data before drug prescription in order to personalize the choice of the therapeutic agent or its dosage. However, such a genomic approach brings economical and ethical questions and will require further progress in our capacity to interpret and store the personal genomic data without compromising their confidentiality. PMID- 26285449 TI - [GENERAL AND PERSONALIZED APPROACH OF BIOMARKERS]. AB - Biomarker determination is very frequently requested to make a diagnosis. The results that are obtained are generally compared with those observed in a <> population, without exactly knowing how this population has been selected. Thus, for a more personalized follow-up of the patient, multiple samples are needed and the reference change values as well as individuality index notions are important to correctly interpret the results. Personalized medicine also encompasses the results obtained by the patient him/herself by means of small analytical devices (self-monitoring), but also with smartphones that can now continuously monitor physical activity or, more generally, health parameters via some applications and devices. Finally, the future of personalized medicine will be the knowledge, for each subject, of all personal biomarkers like DNA and RNA sequences, his/her proteome, metabolome, microbiome, transcriptome, exposome, auto-antibodies and epigenome. PMID- 26285450 TI - [OMICS AND BIG DATA, MAJOR ADVANCES TOWARDS PERSONALIZED MEDICINE OF THE FUTURE?]. AB - The increasing interest for personalized medicine evolves together with two major technological advances. First, the new-generation, rapid and less expensive, DNA sequencing method, combined with remarkable progresses in molecular biology leading to the post-genomic era (transcriptomics, proteomics, metabolomics). Second, the refinement of computing tools (IT), which allows the immediate analysis of a huge amount of data (especially, those resulting from the omics approaches) and, thus, creates a new universe for medical research, that of <> analyzed by computerized modelling. This article for scientific communication and popularization briefly describes the main advances in these two fields of interest. These technological progresses are combined with those occurring in communication, which makes possible the development of artificial intelligence. These major advances will most probably represent the grounds of the future personalized medicine. PMID- 26285451 TI - [BREAST CANCER: FROM TARGETED THERAPY TO PRECISION MEDICINE]. AB - The authors review the principles of systemic therapy in breast cancer. They analyze the degree of treatment individualization in our current approach. New technologies allow the detection of genomic alterations in cancer cells. Unfortunately, we do not know yet how to best use this knowledge for routine patient care. Most genomic alterations are rare events complicating further drug development. Temporal and spatial heterogeneity in tumors also has to be taken into account. An intense international collaboration is ongoing to try and demonstrate that precision medicine will really improve treatment outcome. PMID- 26285452 TI - [SPORADIC SKIN MELANOMA BEYOND ITS NORMATIVE CLASSIFICATION. PLEA CONSIDERING ITS EVOLUTIVE CHARACTERISTICS]. AB - For aeons, cutaneous sporadic melanoma, exhibiting either a slow or rapid growth rate, is identified using a set of well defined histopathological criteria. Such diagnostic step is greatly appreciated, and it brings a rough estimate of the probable evolution of the cancer. Some additional assessments try to improve the progressive prognosis of cutaneous melanoma. In this scope, fractals and spectral analyses expect to better perceive the individual progressive characteristics of each tumor. The extent in the tumoral germinative compartment and the peritumoral microvascular network are explored and should in a near future make clear the progressive potential of cutaneous melanoma. The posible tumoral regression and the immune reaction should be better perceived. PMID- 26285453 TI - [CORONARY ARTERY DISEASE AND HEART FAILURE: A GENOTYPE-BASED THERAPEUTIC APPROACH]. AB - Phenotypic approach of the treatment of coronary artery disease and heart failure used in prospective randomized trials has contributed to significantly improve patieni prognosis. However, gene polymorphisms have been shown to be able to alter treatment efficacy with anti-platelets, beta-blockers or ACE-inhibitors in these settings. As suggested by several studies, therapeutic approaches based on genotype should contribute to personalize treatments with better efficacy and safety. PMID- 26285454 TI - [THE TREATMENT OF HIGH BLOOD PRESSURE MUST BE TAILOR-MADE]. AB - Hypertension has a high world-wide prevalence, affecting more than 25 % of the population; it remains the silent killer number one in cardiovascular pathology. Although lowering high blood pressure is protective, perfect control of hypertension is far from being optimal in spite of many international guidelines regularly updated according to published scientific studies. A personalized approach of hypertension management is an attractive way to improve this situation. Tools are developing (pharmacogenetics, pharmacometabolomics), but their use in daily clinical practice seems premature. At the present time, it is the physician experience which offers the best opportunity to propose the best treatment to the best patient. The management of hypertension remains a difficult task in some cases. Patient education is also crucial to improve drug compliance. PMID- 26285455 TI - [PERSONALIZED APPROACH TO LIPID-LOWERING THERAPY]. AB - Individualized therapeutic strategy of dyslipidemias, classically relies upon a phenotypic approach. The pattern of lipid profile allows the choice of the best pharmacological option (statin, fibrate) and the patient's clinical risk profile allows the definition of therapeutic goals, especially LDL cholesterol target levels. Dyslipidemias have a major genetic component, which is best illustrated by familial hypercholesterolemia, with its two heterozygous and homozygous forms. There is a huge between-subject variability in the response to lipid-lowering therapies (especially to statins) and ongoing pharmacogenetic and pharmacogenomic studies should help to better understand this inter-individual heterogeneity. The recent discovery of mutations in the PCSK9 rene opened new perspectives regarding the understanding of some forms of familial hypercholesterolemia and led to the development of monoclonal antibodies that selectively inhibit PCSK9. These PCSK9 inhibitors allow, when combined to a statin, drastic reductions in LDL cholesterol concentrations, even when familial hypercholesterolemia is present. They are currently tested in large prospective controlled trials aiming to demonstrate a significant reduction in the residual cardiovascular risk in statin treated patients. PMID- 26285456 TI - [FROM EVIDENCE-BASED MEDICINE TO PERSONALIZED MEDICINE: THE EXEMPLE OF TYPE 2 DIABETES]. AB - Type 2 diabetes represents a major medical and public health problem due to its huge heterogeneity, the alarming rise of its incidence worldwide and its associated vascular complications, which impair quality of life and reduce life expectancy. At the present time, a patient-centered approach is recommended for the management of type 2 diabetes patients. However, these recommendations are not easy to implement because we only have little objective evidences to establish individualized strategies. Following the recent introduction of new drug classes, a large number of combinations is offered to clinicians, but we do not have high quality interventional studies comparing these different therapeutic possibilities. Moreover, the response to pharmacological treatment can vary greatly from one subject to the other. Pharmacogenetics might be a useful tool to better characterize the patient. However, despite some progress, the evidence we now have is very preliminary and should not allow to improve significantly the individual management of type 2 diabetes in the near future. PMID- 26285457 TI - [PERSONALIZED TREATMENT OF ASTHMA: THE ISSUE OF ANTI-INTERLEUKIN-5 ANTIBODIES]. AB - Asthma is a chronic inflammatory disease that often features eosinophilia, especially in its most severe forms. Monoclonal antibodies directed towards interleukin-5, such as mepolizumab or reslizumab, were shown to be very effective at reducing blood and airways eosinophilia. When administered monthly by intravenous or subcutaneous injection in severe eosinophilic asthmatic patients, they reduce severe exacerbation rate by 50 %, improve asthma control and quality of life, and have an oral glucocorticoids sparing effect in those requiring oral corticoids as maintenance therapy. PMID- 26285458 TI - [PERSONALIZED MEDICINE: CHRONIC OBSTRUCTIVE PULMONARY DISEASE TREATMENT]. AB - Chronic obstructive pulmonary disease (COPD) is a complex disorder and not all patients respond to all available drugs. The importance of personalized treatment in COPD is inceasingly recognized and, for clinicians, identification of phenotypes represents the first step in this process. The new GOLD does not fully reflect the heterogeneous nature of the disease, but represents a progress in the personalized treatment of COPD. Historically, the two most widely recognized clinical phenotypes of COPD are emphysema and chronic bronchitis. Most COPD patients encountered in practice actually share both of these features. Genetic background, clinical presentation, comorbidities, variation in the response to treatment and propensity to exacerbations may also identify other phenotypes such as the frequent exacerbator,the asthma and COPD overlap syndrome and the persistent systemic inflammation phenotype. A more precise definition of COPD phenotypes should lead to a better targeted therapeutic approach based on these phenotypes. The purpose of this article is to point out that, in COPD, we are moving towards a more personalized therapeutic approach. PMID- 26285459 TI - [FROM EVIDENCE-BASED MEDICINE TO PERSONALIZED MEDICINE IN CROHN'S DISEASE]. AB - The therapeutic armamentarium in Crohn's disease includes mesalazine, steroids (including topical drugs), anti-metabolites (purines, methotrexate), anti TNFalpha antibodies and, more recently, selective inhibitors of lymphocytes homing (vedolizumab). The efficacy of these drugs has been shown in pivotal phase 3 placebo-controlled trials and meta-analyses. However, the use of these drugs in routine practice still remains ill-defined. Those are rather the cohort studies, natural history data and therapeutic strategy trials that help the clinician to determine, for each individual patient, the treatment leading to an optimal benefit/risk profile, aiming at moving from evidence-based medicine towards personalized medicine. PMID- 26285460 TI - [OSTEOPOROSIS AND PERSONALIZED MEDICINE]. AB - Osteoporosis is at the very early stages of the implementation of personalized medicine. However, the development of FRAX(r), an algorithm offering the opportunity to calculate, in an individual patient, his/her 10-year fracture risk improves the decision process on the appropriateness to initiate a pharmacological treatment. This algorithm helps the physician to select drugs which are active on non-vertebral fractures only in high risk patients. Taking into consideration patients' preferences, when selecting a therapeutic option, will improve long term adherence and subsequently efficacy and efficiency of the treatments. Attempts to define the natural course of osteoporosis or the response to therapy in individual patients by assessing their genetic profile remains, so far, inconclusive. PMID- 26285461 TI - [EHLERS-DANLOS SYNDROME OF THE HYPERMOBILE TYPE: A MULTISYSTEMIC DISORDER. CONTRIBUTION OF SKIN ULTRASTRUCTURE TO INDIVIDUAL MANAGEMENT]. AB - Ehlers-Danlos syndrome (EDS) represents a heterogeneous group of disorders of the connective tissue structure. Currently, several types are distinguished following a limited set of clinical signs and genetic mutations. However, there is a lack of specificity of most recognized genetic alterations with the current clinical typing. In addition, the criteria from dermatopathology, ultrastructure and biomechanics are not considered. In addition, the established EDS frontiers are hazardous because a series of anatomo-clinical signs are not considered in the classical EDS concept. The hypermobile type EDS represents an example of the diagnostic uncertainties. It results that guidelines based on evidence-based medicine cannot be established. Only an individual management can be offered to the concerned patients. PMID- 26285462 TI - [MAJOR DEPRESSION AND PERSONALIZED MEDICINE]. AB - Depression is a major public health problem. According to the World Health Organization (OMS), depression is currently the second cause of disability in developing countries. Depression is also one of the most frequent mental illnesses. When treating depression, the main objective is to achieve complete remission and to prevent recurrence. Unfor-tunately, in clinical practice, this aim is particularly difficult to reach. Indeed, in clinical trials and in naturalistic studies, remission levels are rather low. The challenge is to individualize the treatment of depression taking account clinical specificities, but also advances in the field of biological and genetic research. Today, intense psychiatric research tries to discover biomarkers to predict treatment response. Because individuals are highly different from a biological, psychological and sociological point of view, more personalized therapeutic approaches are recommended. PMID- 26285463 TI - [PERSONALIZED MEDICINE : PHARMACOECONOMIC ASPECTS]. AB - The development and establishment of personalized medicine should allow the improvement of the quality of the care services as well as of the development of new and adapted therapeutic solutions. In a society, whose resources for health care are not endless, the issue of costs and economic effectiveness of personalized medicine is important. Numerous pharmacoeconomic studies have been conducted and many of them suggest that personalized medicine leads to better health, but at higher cost. However, the pharmacoeconomic methods developed over recent years will have to be adapted to better take into account the complexity of the problem, especially the capacity and the reliability of tests to best target patients, and also the whole care process of patients. PMID- 26285464 TI - [PERSONALIZED MEDICINE AND EBM: ETHICAL ASPECTS]. AB - More patients are actually treated due to the incredible improvements of medical care, especially in the field of pharmacotherapy. Medical guidelines are based on the results of controlled trials. This kind of medicine, also called Evidence Based Medicine (EBM), is actually the cornerstone of good clinical practice. Nevertheless, it remains a lot of patients disappointed by the fact that they have no medical gain of their treatment. The reason is that each patient has his/her own metabolic characteristics. Better is, the characterization of such patients, better will be the treatment targeting them. It is what is called the personalized medicine. To reach this challenge, pharmacogenetic advances would be helpful. From an antagonism between EBM and personalized medicine, this new medical paradigm has to consider these approaches as partners. To reach this goal, medical doctors, legal authorities and pharmaceutical companies have to be responsible in front of these new ethical challenges. PMID- 26285465 TI - [POLIOMYELITIS ERADICATION--ONE STEP TO ACHIEVE THE GOAL]. AB - Poliomyelitis is a very old disease of humans, caused by poliovirus. With appearance of the epidemics in the 20th century, poliomyelitis became a global public health issue. In 1988, the World Health Organization started a campaign for global eradication of poliomyelitis and till now poliomyelitis cases have been reduced by more than 99%. In Croatia, the introduction of vaccination in 1961 resulted in dramatic reduction of paralytic disease. The European region, including Croatia was certified polio free in 2002. However, the final goal of the "polio-free world" has not yet been reached. To reinforce the campaign, the global polio eradication initiative has come up with the Polio Eradication & Endgame Strategic Plan 2013-2018 with detailed program how to resolve the main challenges: (a) continued transmission of wild polioviruses in endemic reservoirs; (b) reinfection of polio-free areas; and (c) outbreaks due to the circulating vaccine-derived polioviruses (cVDPV). Global oral polio vaccine cessation will follow, with the introduction of universal use of inactivated polio vaccine. PMID- 26285466 TI - [USE OF CONTRACEPTION IN WOMEN FROM THE ZAPRESIC AREA AND FACTORS INFLUENCING THE CHOICE OF METHOD: A CROSS-SECTIONAL STUDY]. AB - There have long been no surveys in the field of family planning in Croatia. There were some carried out by commercial agencies and some related to adolescents, but none focused on women of reproductive age. Therefore, we embarked upon this survey including women living in the town of Zapresic and its surroundings. The aims of the study were to investigate how many of them used contraception, which methods prevailed, how they made their choice and whether demographic and health care characteristics had have any influence on it. This cross-sectional survey was conducted at eight family medicine practices from the town of Zapresic town and six practices from nearby rural settings. We used a purposeful sampling method; women aged 18-45 visiting family medicine practices for different reasons were asked to participate in the study. Those that agreed were given a questionnaire designed for this survey and based on literature results. The questions were closed and related to the women's demographic and some health related characteristics and those related to the usage of contraception, such as the method used, how they made their choice, if they made any changes and why. The STATA/IC 11.2 (license 30110536846) was used on data processing. Descriptive statistics was used with Pearson chi2-test and logistic regression analysis to determine associations between categorical variables and dependent variable, in this case contraception use or non-use. The value of p < 0.05 was considered significant. Out of 283 women having filled in the questionnaire, 44.5% used some contraceptive methods. The most frequently used was condom (24.7%), then pill (24.1%) and combination of several methods (20.0%). The women living in the town used more coitus interruptus, and those living in rural areas used more pills. The most frequently stated reasons for the use of certain methods were as follows: the methods is simple for use (32.9%), it is safe (24.6%), and it is efficient and safe (22.8%). The women with elementary school preferred more efficient and those with high education safer methods. The efficiency of the method was also the main reason for university students. The majority of women made their decision in consultation with gynecologist (48.8%), then in agreement with partner (29.4%) and by her own choice (18.2%). Married and unmarried women made their decision in consultation with gynecologist and partner, unmarried women more with partner than married ones. Only 0.6% of women did consult their family doctors. They did not consider him/her as a professional to consult. In 45.5% of cases, women changed contraceptive methods, more women with high education. Mostly, they wished to use more efficient or safer method. The results of logistic regression analyses indicated that the predictors for contraceptive use were high education, working status, number of abortions and frequency of visits to gynecologist. In conclusion, only 44.5% of surveyed women used contraception, mainly condoms, pills and combination of methods. The efficacy and safety were important reasons, while gynecologists and partners were an important source of help on making decision. The place of living, age, education, married status and working status were associated with some aspects of contraceptive usage. PMID- 26285467 TI - [USE OF COMPLEMENTARY AND ALTERNATIVE MEDICINE AMONG FAMILY MEDICINE PATIENTS- EXAMPLE OF THE TOWN OF CAKOVEC]. AB - The use of complementary and alternative medicine (CAM) is widespread around the world including Croatia. The number of studies that investigate both quantitative and qualitative use of CAM in Croatia is limited. The aim of this study was to investigate the use of CAM among family medicine patients in the town of Cakovec and the rate they report it to their family doctor. This was a cross-sectional study in a sample of 300 patients that visited primary health center for any reason. We used anonymous questionnaire already employed in a previous investigation (Cizmesija et al. 2008), which describes socioeconomic characteristics, modalities of CAM use, and reasons for use. We also added questions on the type of herbs used and use of over-the-counter vitamin and mineral supplements. On data analysis we used descriptive statistics, chi2-test and Fisher's exact test, while the level of statistical significance was set at p <= 0.05. The response rate was 76%. Out of the total number of patients, 82% used some modality of CAM. Women, patients with secondary school education, employed and retired persons used CAM more often. Students and pupils reported least use of CAM. The most commonly used were herbs (87%), bioenergy (29%), diet therapy (28%), chiropractics (22%), and homeopathy and acupuncture (11% each). Vitamin and mineral supplements were used by 77% of study subjects. CAM was most frequently used for respiratory, urinary and musculoskeletal problems, as well as to improve overall health condition. Of the respondents that reported CAM use, 55% believed it would help them, 43% used it because they wanted to try something new, while only 2% indicated dissatisfaction with their physician as the reason for using CAM. Statistically, there were more subjects that used CAM and did not notify their family doctor about it, which could indicate poor communication between family doctors and health care users. Our results are consistent with a previous quantitative study conducted in Croatia and with literature data on the countries with a predominant use of western medicine. Qualitative data from previous studies in Croatia could explain the cultural and socioeconomic context of CAM use. Dissatisfaction with their physician as the reason for using CAM was rarely indicated, suggesting that CAM most probably fills the gap between successful and unsuccessful treatment, and perception that evidence based medicine has its own limitations. The arguments to turn to CAM therapy could involve poor doctor to patient ratio, i.e. 1750 patients per family medicine doctor on average, and the 20% increase in the number of diseases and conditions diagnosed by family medicine units. In conclusion, these results suggest that the use of CAM is common among patients in family medicine. When taking patient history, doctors should ask about CAM use and be aware of the patient beliefs and lifestyle. When patients strongly believe in CAM methods, there is the need of making compromise in therapy, with explanation of the possible side effects and at the same time continuous follow up. There is the need of additional education of family doctors and population about good and bad effects of CAM. In Croatia, accent should be on herbalism because this modality is most widespread. PMID- 26285468 TI - [LOW SPECIFICITY OF PLATELET TO SPLEEN RATIO FOR NONINVASIVE PREDIC- TION AND CHARACTERIZATION OF ESOPHAGEAL VARICES IN PATIENTS WITH ALCOHOLIC LIVER CIRRHOSIS]. AB - Diagnosis of esophageal varices (EV) is based upon endoscopic examination, which is a rather unpleasant method that carries a certain risk of complications. For that reason, efforts have been made to develop noninvasive methods for characterization of EV. The aim of this study was to explore the value of platelet count to spleen size ratio (PSR) for noninvasive prediction and characterization of EV in patients with alcoholic liver cirrhosis (ALC). One hundred and seventeen patients (20 females and 97 males, mean age 60.7) with ALC were included in our research. All patients underwent endoscopic examination upon which the EV were classified as small (< 5 mm), large (> 5 mm), or absent. Spleen size (bipolar diameter in mm) was assessed by ultrasound. Platelet count to spleen diameter ratio was calculated and the values obtained were compared to the presence, size and risk of bleeding from EV as defined by endoscopy. No significant difference in PSR could be found between patients without and with EV (1.341 +/- 0.725 vs. 1.053 +/- 0.636, respectively; p = 0.06). The PSR was significantly different between the patients with small and large EV (1.103 +/- 0.689 vs. 0.876 +/- 0.314; p < 0.05) with a cut-off value of 1.141 (sensitivity 94.7%, specificity 38.2%, AUROC = 0.656; p = 0.042). The value of PSR below 1.182 pointed to patients at risk from variceal bleeding with 91.7% sensitivity and 38.5% specificity (AUROC = 0.625, p = 0.035). Based on our results, it is not possible to recommend the use of PSR as the exclusive noninvasive indicator for the presence, size and bleeding risk from EV due to its low specificity for these categories in patients with ALC. PMID- 26285469 TI - [A STUDY INVESTIGATING THE FACTORS OF INTERNET ADDICTION]. AB - The aim of the study was to explore the characteristics of Internet use among elementary school eighth-graders in the Bjelo- var-Bilogora County, to evaluate gender and sociodemographic differences, and to examine predictors for Internet addiction. The study included 437 (female 51%) eighth-graders, mean age 13.8 +/- 0.5 years. An anonymous questionnaire was used to measure the participants' Internet use, the functions for which they used Internet, their parents' attitude towards the child's Internet use, and their signs of Internet addiction. Logistic regression was conducted to evaluate predictors for Internet addiction. The majority of children (71.5%) reported using Internet every day. Considering important risk factors of Internet addiction development, we found that 32% of children almost always stayed on-line longer than intended, 13% of boys and 4% of girls almost always neglected chores to spend more time on-line and 51.7% of children thought their life would be boring and uninteresting without the Internet. There was no significant difference between urban and rural students. In terms of the function for which they used the Internet, they were mostly engaged in on-line community/chat websites (70%), to listen to music and watch movies (81 %), and boys in gaming websites. Most of the students (43.4%) spent 1 2 hours daily on-line, 26.2% of students spent 3-4 hours on-line, and 9% spent more than 5 hours daily on-line. In conclusion, more public health preventive measures should be conducted to raise public awareness and concern about the negative effect of Internet use and Internet addiction, especially in the young population. PMID- 26285470 TI - [DIABETIC NEPHROPATHY AS A CAUSE OF CHRONIC KIDNEY DISEASE]. AB - Diabetic nephropathy is the leading cause of end-stage chronic kidney disease in most developed countries. Hyperglycemia, hypertension and genetic predisposition are the main risk factors for the development of diabetic nephropathy. Elevated serum lipids, smoking habits, and the amount and origin of dietary protein also seem to play a role as risk factors. Clinical picture includes a progressive increase in albuminuria, decline in glomerular filtration, hypertension, and a high risk of cardiovascular morbidity and mortality. Screening for albuminuria should be performed yearly, starting 5 years after diagnosis in type 1 diabetes or earlier in the presence of adolescence or poor metabolic control. In patients with type 2 diabetes, screening should be performed at diagnosis and yearly thereafter. Patients with albuminuria should undergo evaluation regarding the presence of associated comorbidities, especially retinopathy and macrovascular disease. Achieving the best metabolic control (HbA1c < 7%), treating hypertension (target blood pressure < 140/85 mm Hg), using drugs with blockade effect on the renin-angiotensin-aldosterone system, treating dyslipidemia and anemia are effective strategies for preventing the development of albuminuria, delaying the progression to more advanced stages of nephropathy and reducing cardiovascular mortality in patients with type 1 and type 2 diabetes. PMID- 26285471 TI - [PREOPERATIVE DIAGNOSTICS OF THYROID MEDULLARY CARCINOMA WITH EMPHASIS ON CYTOMORPHOLOGICAL FEATURES AND DIFFERENTIAL DIAGNOSIS OF PRIMARY AND SECONDARY THYROID TUMORS]. AB - Medullary thyroid cancer is a rare neuroendocrine neoplasm that arises from the parafollicular C cells that produce calcitonin, a hormone essential for the regulation of calcium metabolism. It accounts for 4%-10% of all thyroid cancers. In most cases (75%-80%), it is sporadic, while in other cases it is part of the multiple endocrine neoplasia (MEN) syndrome. Most often, medullary thyroid carcinoma is presenting as a solitary nodule. At the time of diagnosis, about half of the patients have enlarged cervical lymph nodes, while a small number of patients have distant metastases in the liver, lungs, bones and brain. If the tumor is hormone active, the patient may have systemic symptoms such as diarrhea or flushing. Ultrasonically, medullary carcinoma usually appears as a hypoechogenic node with marked vascularity and uneven contours that can sometimes contain microcalcifications, and in most cases is located in the upper poles of the thyroid. The sample obtained by fine needle aspiration is usually cellular, tumor cells are disseminated or arranged in poorly cohesive groups. They are most often plasmacytoid, but sometimes can also be spindled. The nuclei are eccentric and chromatin shows features of neuroendocrine tumors. Cytoplasms of tumor cells are abundant, triangular or polygonal, amphophilic, finely granulated and unsharply limited. Background is clean and sometimes amyloid can be found. Depending on the cytologic picture, differential diagnostic problems can be well differentiated thyroid tumors, primarily follicular neoplasm, lymphomas, poorly differentiated insular carcinoma, metastatic small cell carcinoma, mesenchymal tumors or melanoma. In case of differential diagnostic difficulties, of great help is to determine calcitonin immunocytochemically or in aspirate or serum. Medullary carcinoma may show low progression and long-time survival, but can also be a rapidly progressive tumor where survival is measured in months. Good prognostic indicators are younger age, female gender, tumor size, tumor localization only in the thyroid gland, and absence of local or distant metastases. In conclusion, medullary thyroid carcinoma is a rare tumor in which we still have to think in diagnosing thyroid nodules, mainly due to adequate preoperative preparation in terms of exclusion of pheochromocytoma in MEN syndrome. Cytologic picture in some cases is typical; however, immunocytochemical evidence of calcitonin is of great help to confirm morphological diagnosis. PMID- 26285472 TI - [TREATMENT MODALITIES OF LABIAL FUSION IN PREPUBERTAL GIRLS]. AB - Labial adhesion is a thin membranous fusion of the labia minora of varying length. It is not a rare condition in prepubertal girls, but since it is often asymptomatic, it remains undiagnosed. It is usually discovered during regular check-ups or when the fusion results in post-void dripping, bacteriuria, vaginal irritation, dysuria, urinary tract infection or obstruction. The cause of labial adhesions is unclear. Chronic irritation of the vulva in combination with poor hygiene is believed to be important etiologic factors. A theory of hypoestrogenic status in prepubertal girls as a potential etiologic factor for labial adhesions is no longer widely accepted, since a recent study concluded that there was no difference in estrogen levels between children with and those without labial adhesions. Treatment options include conservative management with topical estrogen or betmethasone creams or, when indicated, manual separation or surgery. Topical estrogen and betamethasone creams are generally considered safe and effective treatment of labial adhesions, even over prolonged periods of time, with minimal if any side effects. No guidelines have been structured for the limits or duration of topical therapy, but most authors agree that optimal treatment should last from 1 to 2 or 3 months on twice-a-day regimen. Parental education concerning appropriate application technique is important not only for the success of treatment, but also to avoid the possible side effects. PMID- 26285473 TI - [TICK-BORNE ENCEPHALITIS VIRUS: EPIDEMIOLOGICAL AND CLINICAL PICTURE, DIAGNOSIS AND PREVENTION]. AB - Tick-borne encephalitis virus (TBEV) is a small, enveloped virus that belongs to the family Flaviviridae, genus Flavivirus, tick-borne encephalitis serocomplex. There are three subtypes of TBEV: European, Far-Eastern and Siberian subtypes, which differ in geographical distribution, tick vector and clinical manifestation of disease in humans. TBEV is endemic in a wide geographic area ranging from Central Europe and the Scandinavian Peninsula to Japan. The virus is maintained in nature in so-called natural foci in cycles involving ticks and wild vertebrate hosts (mainly small rodents). The principal vector for the European subtype is Ixodes (I.) ricinus tick, whereas for Far-Eastern and Siberian subtypes it is I. persulcatus. In the Baltic States and Finland, co-circulation of two or all three subtypes was documented. Several animals, principally small rodents, serve as virus reservoirs. In the tick population, TBEV is transmitted by feeding/co-feed ing on the same host, transovarially (from infected females to their eggs) and trans-stadially (from one development stage to the next). An infected tick remains infected for life. While most TBE infections in humans occur following a tick bite, alimentary routes of TBEV transmission (consumption of unpasteurized milk/milk products from infected livestock) have also been described. All three tick stages can transmit the infection to humans. In the last decade, an increase of TBE incidence has been observed in some endemic areas. This could be due to a number of interacting factors such as changes in the climatic conditions affecting tick habitats, improvements in the quality of epidemiological surveillance systems and diagnostics, in landscape resources and their utilization and more outdoor recreation activity. In addition, the endemic area of TBEV has expanded to higher altitudes (up to 1500 m), apparently influenced by climatic changes. The typical clinical picture of infection with European subtype TBEV is characterized by a biphasic course (50%-77%). The first phase is characterized by nonspecific, flu-like symptoms followed by an asymptomatic interval of about one week. In 20%-30% of persons who develop symptoms, the second phase occurs with symptoms of central nervous system involvement (meningitis, encephalitis, myelitis, radiculitis). The mortality rate for European subtype is 1%-2%. Diagnosis is usually based on detection of specific antibodies (enzyme immunoassay, indirect immunofluorescent assay, plaque reduction neutralization test). From 1993 to 2013, a total of 777 cases of TBE were reported in Croatia. Endemicity is highest in north-western counties (mean incidence 3.61-6.78/100,000 inhabitants). The majority of patients were older than 20 years (88%). Most cases (73%) were reported from May to July. PMID- 26285474 TI - [GIANT CELL TUMOR OF BONE: RESULTS AND TREATMENT COMPLICATIONS]. AB - Giant cell tumor of bone (GCT) is mostly benign, locally aggressive tumor with a high recurrence rate. GCT is treated primarily surgically, and the approach is determined according to localization and local tumor behavior. The aim of this study was to analyze results and complications of surgical treatment of GCT at atertiary orthopedic clinical center in Croatia. We analyzed all patients treated at University Department of Orthopedics, Zagreb University Hospital Center, during a 15-year period. From 1995 to 2009, 39 patients were surgically treated for GCT. Four patients were lost from follow up. In patients with low-grade GCT (n = 12, 34%), we performed marginal-intralesional resection, whereas in patients with locally aggressive GCT we performed en bloc resection and reconstruction with tumor endoprosthesis or bone allograft (n = 22, 63%). In one patient, the only treatment was tumor irradiation. Complications were evident in one-third of our patients. The most common complications were tumor recurrence (n = 6, 50% of all complications) and deep infection (n = 2, 17% of all complications). We performed amputation in two patients in whom osteosarcoma was revealed under GCT radiologic and histologic appearance. We performed 84 operations in 35 patients, not counting primary biopsy. In conclusion, treatment of GCT is complex, with a high incidence of tumor recurrence. Diagnosis and treatment are best provided through a multidisciplinary approach in highly specialized centers for orthopedic oncology. PMID- 26285475 TI - [OUR RESULTS IN LAPAROSCOPIC-ASSISTED PLACEMENT OF PERITONEAL DIALYSIS CATHETERS: TEN-YEAR EXPERIENCE]. AB - The aim was to analyze our results and complications in laparoscopic-assisted placement of the Tenckhoff catheter for peritoneal dialysis in comparison with results reported in the literature. Fifty patients were included in this retrospective analysis. From January 2000 to November 2010, they underwent laparoscopic-assisted placement of catheter for peritonea dialysis at the University Department of Surgery, Rijeka University Hospital Center. The results of this approach, early and late postoperative complications, conversions to open technique, and reoperation rate were analyzed. The complications that occurred within the first 4 weeks were considered as early complications. In 23 patients, 29 complications were recorded. There were 18 early complications, of which 2 acute peritonitis, 2 ileus, 4 bleeding, 4 catheter infection, 3 fluid leakage, 2 catheter malpositioning and 1 genital edema. There were 11 late complications, of which 5 acute peritonitis, 1 recurrent peritonitis, 1 bleeding, 1 catheter infection, 1 catheter malpositioning, 1 fluid leakage and 1 port site hernia. There were no deaths after surgery or any complications disabling the implementation of peritonea dialysis. In patients with end-stage renal disease, laparoscopic-assisted placement of catheter for peritoneal dialysis is a safe and appropriate method of treatment PMID- 26285476 TI - [ENTERIC DUPLICATION CYST IN NEONATAL PERIOD: CASE REPORT]. AB - In recent decades, diagnosis of neonatal malformations has shown growing success thanks to advances in ultrasound diagnostics. Intra-abdominal cystic formation can be successfully diagnosed prenatally, most often in the third trimester, mainly as isolated unilateral lesions in otherwise healthy fetus. With the existence of intra-abdominal cyst in neonate, it is necessary to exclude urinary tract anomalies and abnormalities of the heart and the spine. We present diagnostic procedure and perinatal outcome of a female newborn with enteric duplication cyst. PMID- 26285477 TI - [METHODS FOR DETECTION OF ANTIBODIES TO HLA ANTIGENS IN PATIENTS AWAITING KIDNEY TRANSPLANTATION AND COMBINED PANCREAS-KIDNEY TRANSPLANTATION]. AB - The best possibility to treat chronic renal disease is renal transplantation. Especially important fact in transplantation is the percentage of so-called panel reactive antibody (PRA) that is focused on the human leukocyte antigen. There are several methods to determine the percentage of PRA in sensitized patients awaiting kidney transplants. The most important is the complement-dependent cytotoxicity. A higher value of PRA implies greater likelihood of positive cross match with random donor and lower probability of receiving a transplant. Comparing the sensitivity of laboratory tests for determination of PRA percentage in patient serum, it is concluded that ELISA and flow cytometry proved to be more sensitive and specific. PMID- 26285478 TI - [FIRST OPERATION ON OPEN HEART IN HYPOTHERMIA PERFORMED IN CROATIA IN 1957]. AB - On October 25, 1957, the first open heart surgery in hypothermia was performed in Zagreb, at the Department of Surgery, Dr. Ozren Novosel University Hospital (now Merkur University Hospital), in a female patient with pulmonary valve stenosis under the control of the eye and with interruption of venous circulation. It was the first such operation performed in hypothermia not only in Croatia, but probably in the territory of former Yugoslavia. PMID- 26285479 TI - [Behind the scenes of expert discussion on efficiency of implementation program of delaying of early drinking in adolescents in Croatia]. PMID- 26285480 TI - NEW APPROACHES TO TREATMENT. THE BIGGEST CHANGES IN 20 YEARS ARE COMING. PMID- 26285481 TI - CHASING THE CURE. THE STATE OF THE SEARCH IN 2015. PMID- 26285482 TI - A new look at how HIV works. A biologist turned animator offers new insight. PMID- 26285483 TI - [The work of the doctor in times of crisis]. PMID- 26285484 TI - [Interactions between markers of endothelial damage (homocysteine and asymmetric dimethylarginine) and antioxidants and B-vitamins in preeclamptic women]. AB - BACKGROUND: Preeclampsia is a pregnancy-related pathological condition triggered by an abnormal placentation which produces endothelial dysfunction (ED). ED, in turn, is associated with an increase in homocysteine (hcy) and asymmetric dimethylarginine (ADMA); these molecules are also increased when some of the B vitamins are deficient. It is unclear whether increases in hcy and ADMA during preeclampsia are the result of ED, or the consequence of a B-vitamin deficiency. OBJECTIVE: To evaluate hcy, ADMA, folic acid (FA), vitamin B6 and B2 concentrations in patients with preeclampsia. METHODS: In a cross-sectional design 19 patients with severe preeclamp- sia (preeclampsia) and 57 with normal pregnancy (no-preeclampsia), paired by gestational age and body mass index, were studied. Plasma hcy, ADMA, FA and vitamins B6 and B12 were determined. Non parametric statistics was used for between-groups comparisons and regression analyses to evaluate interactions among molecules. RESULTS: 72% of women were vitamin B deficient, 40% were deficient of B12 and 4% of FA. Preeclamptic patients presented hcy and ADMA concentrations higher than no-preeclamptic ones. Inferential analyses demonstrated that: hcy and ADMA are increased during preeclampsia independently from vitamins blood concentration; that the risk for pre- eclampsia is associated with high hcy but not with vitamins deficiency; and that the ratio L-arginine:ADMA decreases the preeclampsia risk. CONCLUSION: In patients with preeclampsia, increases of hcy and ADMA are associated with ED, but not with deficiency of the vitamins involved in their metabolism. PMID- 26285485 TI - [Intrauterine synechiae after use of monopolar resectoscope]. AB - BACKGROUND: Uterine synechiae are defined as abnormal adhesions and fibrosis within the uterine cavity due to direct trauma or injury to the basal membrane of the endometrium. OBJECTIVE: To identify, by routine hysteroscopy, how many patients who were treated because of intrauterine pathology developed uterine synechiae within the first six months after treatment with monopolar resectoscope. MATERIAL AND METHOD: A descriptive, open, observational, retrospective and cross-sectional study was performed at Hysteroscopy Unit, Gynecology Service of General Hospital Manuel Gea Gonzalez, Mexico City. From January 1, 2008 to December 31, 2011, we took, from the record books of the operating rooms, the file number of those patients who were treated with monopolar resectoscopy, and subsequently underwent routine hysteroscopy within the first six months. RESULTS: 69 records were included in the study. The main diagnoses were: endometrial polyp in 48% (n=33), submucosal myoma in 45% (n=3 1); 48% (n=33) polypectomy and 45% (n=31) myomectomy. Within the first six months after the main procedure, patients underwent a routine hysteroscopy, which revealed the development of intrauterine synechiae in 5.8% (n=4) of the patients. Of the patients who underwent myomectomy, 5.8% (n=4) developed uterine synechiae; while those patients who underwent polypectomy, synechiaes were not found. Minimal synechiaes were found in 4.3% (n=3) of patients, moderate synechiaes were found in 1.4% (n=1) of patients, and severe synechiaes were found in none patient. CONCLUSION: Uterine synechiaes were found in 5.8% of patients with intrauterine pathology and treated with monopolar resectoscopy. Minimal to moderate synechia occur more commonly after myomectomy. PMID- 26285486 TI - [Non-surgical management of rectovaginal fistula: a case report]. AB - BACKGROUND: The rectovaginal fistula is a rare disease whose treatment is extremely difficult. OBJECTIVE: To present the expectant management of rectovaginal fistula as an alternative to surgery for those cases in which the surgical risk is not an acceptable option. CLINICAL CASE: We report the case of a rectovaginal fistula in an 85-year-old woman with significant comorbidity that avoided the performance of any surgical technique. CONCLUSION: In patients whose surgical risk does not exceed the benefits, non-surgical management would be an option of treatment of rectovaginal fistula. PMID- 26285487 TI - [Extra-abdominal umbilical vein varix. A case report]. AB - The intra-abdominal umbilical vein varix is very uncommon, characterized by a dilation of the vein, usually located between its entry into the abdomen and completion in the portal system. However, the location of this anomaly to extra abdominal level is very unusual and more difficult to diagnose by ultrasound. CLINICAL CASE: We present a case undiagnosed during pregnancy, demonstrating cord abnormality in its extra-abdominal portion and confirmed later by the pathology study. It was a gestation of 36 + 6 weeks, ending by performing emergency caesarean section for abnormal fetal heart rate, with good perinatal outcome. The diagnosis was made after placental delivery, by the existence of fibrotic cystic structure in the middle third of the umbilical cord. PMID- 26285490 TI - Health Sciences Grants Change Learning at U-M. PMID- 26285489 TI - Learn About Your Life Insurance Options. PMID- 26285488 TI - [Consensus of diagnosis and treatment of obesity in women in reproductive age and climacterium]. AB - BACKGROUND: The development of obesity is complex and multifactorial, with genetic, biological, environmental and lifestyle of each individual etiology. The different changes in metabolism of women, amongst other factors, lead to disorganization in the distribution of lipids, which gathered in large quantities within the viscera, increases cardiovascular mortality and it is a major determinant factor of the metabolic syndrome. OBJECTIVE: To homologate and to apply concepts of evidence-based clinical practice in diagnosis and treatment of obesity in women in reproductive age and climacterium. METHOD: The experts' consensus was done by specialized physicians properly endocrinologists, gynecologists, surgeons, psychologists, nutrition specialists, physical activity and public health, according to their expertise and clinical judgment. The recommendations were based in diagnostic criteria aside from the level of evidence of previously established treatment guidelines, controlled clinical trials and standardized guides for women in reproductive age and climacterium with obesity. RESULTS: The establishment of a nutritional intervention amongst other aspects of lifestyle is the first-line in the treatment of obesity. Current pharmacological treatments offer modest results in efficiency and security in weight reduction so these must go along with real changes in lifestyle in order to obtain better results in the short and long term. CONCLUSION: The high prevalence of overweight and obesity in our country, especially in women in reproductive age, compels us to pose and work in prevention strategies as well as diverse therapeutic plans favoring safe weight loss and results in the long term. PMID- 26285491 TI - Get Ready! National Children's Dental Health Month Is Coming. PMID- 26285492 TI - Loan Repayment Program Assists Dentists. PMID- 26285493 TI - Disappointed at Commentary. PMID- 26285494 TI - Author reply: To PMID 25647877. PMID- 26285495 TI - Sterilization Pouches, Bibs and More Added to MDA Services Gloves. PMID- 26285496 TI - Personal Accident Insurance Helps Pay Deductibles, Other Expenses. PMID- 26285497 TI - Take Advantage of the New MDA Public Education Campaign. PMID- 26285498 TI - Dealing with Patients Who Have Been Using Marijuana. PMID- 26285500 TI - Is Change Possible? PMID- 26285499 TI - Is This Thing On? Recording Conversations in the Workplace. PMID- 26285502 TI - Periodontal Considerations for the Child and Adolescent. A Literature Review. AB - The primary etiology of periodontal disease is bacterial plaque and its byproducts in a susceptible host. Although the prevalence of plaque-induced periodontal disease is relatively low for the child and adolescent, destructive periodontal disease may be a manifestation of an underlying systemic disease. In some cases, childhood periodontal destruction may be the first sign of systemic disease, making appropriate recognition and determination of etiology critical in this population. Therefore, this literature review discusses the periodontal considerations for the child and adolescent patient, aiming to offer a guide for differential diagnosis and oral management of periodontal disease in the young population. PMID- 26285501 TI - Pediatric Dentistry: Beginning a Lifetime of Dental Health. PMID- 26285503 TI - Facial Dog Bite Injuries of a 19-Month-Old Child: A Case Report. AB - It is estimated that 4.5 million Americans are bitten by dogs each year, and half of those are children. One in five dog bites results in injuries that require some form of medical attention. Children between 5 and 9 years of age are the most affected age group for this type of injury. A 19-month-old boy was admitted to the emergency department of Children's Hospital of Michigan for treatment of injuries due to a dog attack. Injuries were limited to the face of the child. Dental injuries included avulsion of upper lateral incisors, severe luxation of upper central incisors, and fracture of the facial alveolus bone. Surgical management of facial wounds was accomplished through irrigation, debridement and suturing. Dental treatment included extraction of central incisors and suturing soft tissues. PMID- 26285504 TI - Michigan Dentists' Attitudes toward Medicaid and an Alternative Public Dental Insurance System for Children. AB - PURPOSE: Healthy Kids Dental (HKD) was created as a pilot program of the Michigan State Medicaid program to increase access to care for Medicaid-eligible children. The purpose of this study was to evaluate dentists' attitudes toward Healthy Kids Dental and Medicaid in Michigan. METHODS: An online survey was sent to practitioners with an email address registered with the Michigan Dental Association (n=4,285). RESULTS: Surveys were returned from 965 practitioners (~23 percent). Although practitioners were not fully satisfied with HKD, their satisfaction with the program was significantly higher than their satisfaction with the traditional Medicaid program (P<.001). Sixty-four percent of providers that accept Medicaid limit the number of children seen in some manner, while 28 percent of providers that accept HKD limit the number of children seen. Families with traditional Medicaid who contact an office are significantly less likely to receive treatment for their child than families with HKD insurance who contact the same office (P<.001). CONCLUSIONS: Practitioners were more satisfied with programmatic and patient-related factors of the Healthy Kids Dental program than they were with Medicaid. Dentists were more likely to treat children with HKD than children with Medicaid when the parent contacts a dentist in Michigan. PMID- 26285505 TI - Business Planning: How to Become a More-effective Practice Owner. PMID- 26285512 TI - Reminder: Dentists Are Mandated Abuse, Neglect Reporters. PMID- 26285513 TI - ADA Launches Fluoride Initiatives. PMID- 26285514 TI - Comments on "Cooking the Books". PMID- 26285515 TI - Dr. Maihofer responds. PMID- 26285521 TI - Is There a Need for 24-Hour Walk-in Dental Care? PMID- 26285522 TI - Miscellaneous Dental Practice Questions. PMID- 26285523 TI - Vaping in the Workplace: E-Cigarettes and Your Smoking/Tobacco Policy. PMID- 26285524 TI - The Case of the Kissing Dentist. PMID- 26285525 TI - Can you weather the financial storm of musculoskeletal disorders. PMID- 26285527 TI - Oral and Maxillofacial Pathology Case of the Month. PMID- 26285526 TI - An Interview with Dr. Mark Johnston 2015-16 MDA President. PMID- 26285528 TI - What Are We Teaching Dental Students about Practice Management? PMID- 26285529 TI - Hire Your Spouse? What to Consider Before You Say 'I Do'. PMID- 26285532 TI - Religious Accommodation Requests and Dress Code Policies. PMID- 26285531 TI - Sedation: Patient Safety and Informed Consent. PMID- 26285533 TI - Going After Unethical Advertisers. PMID- 26285534 TI - Focused Review--Revisited. PMID- 26285535 TI - Is Organized Dentistry Following Medicine Down the Drain? PMID- 26285536 TI - "Change, Progress and Continuous Improvement at the MDA"! PMID- 26285537 TI - Seven Cases of Proliferative Verrucous Leukoplakia: The Need for a High Clinical Suspicion Among Dental Practitioners. AB - Proliferative verrucous leukoplakia is a distinct precancerous condition with a high rate of recurrence and malignant transformation over time. Proliferative verrucous leukoplakia has no specific histopathologic presentation; therefore, emphases must be on clinical presentation and history to make a diagnosis giving the need for a high clinical suspicion. This condition is very important for the general dentist to recognize. Here we describe the clinical and microscopic features of seven cases of proliferative verrucous leukoplakia, with two cases which demonstrated malignant transformation (hybrid carcinoma and squamous cell carcinoma). PMID- 26285539 TI - Opportunities for influence post-Election. PMID- 26285540 TI - Challenging schedule for Ontario facility. PMID- 26285541 TI - Recognising design's role in reducing HAIs. PMID- 26285542 TI - Ambitious goals met, but more to achieve. PMID- 26285543 TI - Being clearer about estate requirements. PMID- 26285544 TI - Improving confidence to manage assets. PMID- 26285545 TI - Designed with multidisciplinary input. PMID- 26285546 TI - Preventing scalding/controlling Legionella. PMID- 26285548 TI - Event to reflect 'service user-led thinking'. PMID- 26285547 TI - Providing a better experience for all. PMID- 26285549 TI - Emergency generators' critical role examined. AB - The research evidence cited within this article relates to the reliability of emergency diesel generators, and concludes by recommending that NHS organisations urgently review their corporate strategy, business continuity plans, backlog maintenance schedules, etc., as it appears that these units are not operating to the 99.95% reliability figure suggested by the National Approved Codes of Practice (ACOP), but instead at reliabilities of around 98.5%. The practical interpretation of this lower reliability figure is that for a typical NHS Trust operating 10 emergency diesel generators, it can be surmised that they can expect to experience 1.81 failures/year, while under test conditions When combining the requirements for the generators to operate under test plus actual power outage conditions, with the 'fragility' of the power supply from the main electrical undertaker, then the Trust can expect to experience >1.81 failures/year, some of which could occur during a power outage. In putting together this article I conducted a small 'straw poll' of NHS acute hospital sites, which confirmed that the failure of emergency diesel generators was far from being a rare event, and indeed when the historical records were compared with the research papers cited, they showed that such failures were predictable, and in most cases preventable, i.e. certain. PMID- 26285550 TI - Multiple settings are targeted in pilots. PMID- 26285551 TI - A 'disaster prevention' approach advocated. PMID- 26285552 TI - Canopy considerations for cleaner airflow. PMID- 26285553 TI - Assessing the risks, taking the right steps. PMID- 26285554 TI - Guy's Cancer Centre takes shape. PMID- 26285555 TI - Good fire strategies are no accident. PMID- 26285556 TI - An appetite for making things better. PMID- 26285557 TI - System choice is greater than ever. PMID- 26285558 TI - Building on solid ground. PMID- 26285560 TI - Protection for the profession. PMID- 26285561 TI - Codes deserve careful examination. PMID- 26285562 TI - Moving towards a mandate. PMID- 26285563 TI - From haute couture to the FDI. PMID- 26285564 TI - Timing is everything. PMID- 26285565 TI - A frontal swelling with a cautionary tale. AB - Frontal sinus mucoceles are the most common paranasal mucoceles. They consist of sterile mucus and shed cells and form due to inflammatory changes or chronic nasofrontal duct obstruction. Coincident infection and expansile growth can lead to specific clinical features dependent upon the location of the lesion and the degree of spread. We present a case of a 56-year-old lady with a radiological diagnosis of a frontal sinus mucocele causing anterior dehiscence of her frontal cortex. She underwent incision and drainage of a frontal swelling misdiagnosed as an infected sebaceous cyst. The case emphasises the importance of correlating features in the patient history and previous investigations with presenting findings. PMID- 26285566 TI - Ebola virus disease: review and implications for dentistry in Ireland. AB - The current Ebola outbreak in West Africa is a global health emergency with implications for all healthcare professionals. This article will review the clinical features, transmission and oral manifestations of Ebola virus infection, and discuss the implications of the current outbreak for dental practices in Ireland. Guidance for managing suspected cases and contacts is also provided. CONCLUSIONS: Although Ebola is an alarming disease with a very high mortality rate, it is extremely unlikely that the dental team will encounter a new presentation of Ebola or that it will pose a significant transmission risk. The dental team should be aware of the Health Protection Surveillance Centre (HPSC) Algorithm for Ebola Virus Disease Risk Assessment, and it should be followed as necessary. It is advised to defer dental treatment for 21 days after possible exposure to the Ebola virus. PMID- 26285567 TI - Mandibular implant-supported overdentures: attachment systems, and number and locations of implants--Part II. PMID- 26285568 TI - Press-fit fixation using autologous bone in the tibial canal causes less enlargement of bone tunnel diameter in ACL reconstruction--a CT scan analysis three months postoperatively. AB - BACKGROUND: Bone tunnel enlargement is a phenomenon present in all anterior cruciate ligament (ACL)- reconstruction techniques. It was hypothesized that press-fit fixation using a free autograft bone plug reduces the overall tunnel size in the tibial tunnel. METHODS: In a prospective cohort study twelve patients who underwent primary ACL reconstruction using an autologous quadriceps tendon graft and adding a free bone block for press-fit fixation (PF) in the tibial tunnel were matched to twelve patients who underwent ACL reconstruction with a hamstring graft and interference screw fixation (IF). The diameters of the bone tunnels were analysed by a multiplanar reconstruction technique (MPR) in a CT scan three months postoperatively. Manual and instrumental laxity (Lachman test, Pivot-shift test, Rolimeter) and functional outcome scores (International Knee Documentation Committee sore, Tegner activity level) were measured after one year follow up. RESULTS: In the PF group the mean bone tunnel diameter at the level of the joint entrance was not significantly enlarged. One and two centimeter distal to the bone tunnel diameter was reduced by 15% (p = .001). In the IF group the bone tunnel at the level of the joint entrance was enlarged by 14% (p = .001). One and two centimeter distal to the joint line the IF group showed a widening of the bone tunnel by 21% (p < .001) One and two centimeter below the joint line the bone tunnel was smaller in the PF group when compared to the IF group (p < .001). No significant difference for laxity test and functional outcome scores could be shown. CONCLUSION: This study demonstrates that press-fit fixation with free autologous bone plugs in the tibial tunnel results in significantly smaller diameter of the tibial tunnel compared to interference screw fixation. PMID- 26285569 TI - Demographic and obstetric factors affecting women's sexual functioning during pregnancy. AB - BACKGROUND: Sexual desire and frequency of sexual relationships during pregnancy remains challenging. This study aimed to assess factors that affect women's sexual functioning during pregnancy. METHODS: This was a cross sectional study carried out at prenatal care clinics of public health services in Iran. An author designed structured questionnaire including items on socio-demographic characteristics, obstetric history, the current pregnancy, and women's sexual functioning during pregnancy was used to collect data. The generalized linear model was performed in order to find out factors that affect women's sexual functioning during pregnancy. RESULTS: In all, 518 pregnant women participated in the study. The mean age of participants was 26.4 years (SD = 4.7). Overall 309 women (59.7%) scored less than mean on sexual functioning. The results obtained from generalized linear model demonstrated that that lower education, unwanted pregnancy, earlier stage of pregnancy, older age, and longer duration of marriage were the most important factors contributing to disturbed sexual functioning among couples. CONCLUSION: The findings suggest that sexual function during pregnancy might be disturbed due to several factors. Indeed issues on sexual relationship should be included as part of prenatal care and reproductive health programs for every woman. PMID- 26285570 TI - Erratum: Feasibility and acceptability of a novel, computerized screening and brief intervention (SBI) for alcohol and sweetened beverage use in pregnancy. PMID- 26285571 TI - Histological criteria for atypical pituitary adenomas - data from the German pituitary adenoma registry suggests modifications. AB - INTRODUCTION: The term atypical pituitary adenoma (APA) was revised in the 2004 World Health Organization (WHO) classification of pituitary tumors. However, two of the four parameters required for the diagnosis of APAs were formulated rather vaguely (i.e., "extensive" nuclear staining for p53; "elevated" mitotic index). Based on a case-control study using a representative cohort of typical pituitary adenomas and APAs selected from the German Pituitary Tumor Registry, we aimed to obtain reliable cut-off values for both p53 and the mitotic index. In addition, we analyzed the impact of all four individual parameters (invasiveness, Ki67 index, p53, mitotic index) on the selectivity for differentiating both adenoma subtypes. METHODS: Of the 308 patients included in the study, 98 were diagnosed as APAs (incidence 2.9 %) and 10 patients suffered from a pituitary carcinoma (incidence 0.2 %). As a control group, we selected 200 group matched patients with typical pituitary adenomas (TPAs). Cut-off values were attained using ROC analysis. RESULTS: We determined significant threshold values for p53 (>=2 %; AUC: 0.94) and the mitotic index (>=2 mitosis within 10 high power fields; AUC: 0.89). The most reliable individual marker for differentiating TPAs and APAs was a Ki-67-labeling index >= 4 % (AUC: 0.98). Using logistic regression analysis (LRA) we were able to show that all four criteria (Ki-67 (p < 0.001); OR 5.2// p53 (p < 0.001); OR 3.1// mitotic index (p < 0.001); OR 2.1// invasiveness (p < 0.001); OR 8.2)) were significant for the group of APAs. Furthermore, we describe the presence of nucleoli as a new favorable parameter for TPAs (p = 0.008; OR: 0.4; CI95 %: 0.18; 0.77). CONCLUSIONS: Here we present a proposed rectification of the current WHO classification of pituitary tumors describing an additional marker for TPA and specific threshold values for p53 and the mitotic index. This will greatly help in the reliable diagnosis of APAs and facilitate further studies to ascertain the prognostic relevance of this categorization. PMID- 26285572 TI - Expression of truncated human epidermal growth factor receptor 2 on circulating tumor cells of breast cancer patients. AB - INTRODUCTION: The truncated form of human epidermal growth factor receptor 2 (p95HER2) lacks the HER2 extracellular domain and has been associated with poor prognosis and resistance to trastuzumab. In the present study, the expression of p95HER2 was investigated on circulating tumor cells (CTCs) from breast cancer patients. METHODS: Triple-staining immunofluorescent experiments were performed on peripheral blood mononuclear cells' (PBMCs) cytospins obtained from patients with early (n = 24) and metastatic (n = 37) breast cancer. Cells were stained with the pancytokeratin (A45-B/B3) antibody coupled with antibodies against the extracellular (ECD) and the intracellular (ICD) domains of HER2. Slides were analyzed with either confocal laser scanning microscopy or with the Ariol system. RESULTS: HER2-positive CTCs were identified in 55.6 % of early and 65.2 % of metastatic CTC-positive breast cancer patients. p95HER2-positive CTCs were identified in 11.1 % of early and 39.1 % of metastatic breast cancer patients (p = 0.047). In 14 patients with metastatic HER2-positive breast cancer, CTCs were also analyzed before and after first-line trastuzumab therapy. Trastuzumab reduced the percentage of patients with full-length HER2-positive CTCs from 70 % at baseline to 50 % (p = 0.035) after treatment while increased the percentage of patients with p95HER2-positive CTCs from 40 % to 63 %. Moreover, the overall survival of metastatic patients with p95HER2-positive CTCs was significantly decreased (p = 0.03). CONCLUSIONS: p95HER2-positive CTCs can be detected in both early and metastatic breast cancer patients. Their incidence is increased in the metastatic setting and their presence is associated with poor survival. Longitudinal studies during anti-HER2 treatment are required to determine the clinical relevance of p95HER2-expressing CTCs. PMID- 26285573 TI - Characterization of a second secologanin synthase isoform producing both secologanin and secoxyloganin allows enhanced de novo assembly of a Catharanthus roseus transcriptome. AB - BACKGROUND: Transcriptome sequencing offers a great resource for the study of non model plants such as Catharanthus roseus, which produces valuable monoterpenoid indole alkaloids (MIAs) via a complex biosynthetic pathway whose characterization is still undergoing. Transcriptome databases dedicated to this plant were recently developed by several consortia to uncover new biosynthetic genes. However, the identification of missing steps in MIA biosynthesis based on these large datasets may be limited by the erroneous assembly of close transcripts and isoforms, even with the multiple available transcriptomes. RESULTS: Secologanin synthases (SLS) are P450 enzymes that catalyze an unusual ring-opening reaction of loganin in the biosynthesis of the MIA precursor secologanin. We report here the identification and characterization in C. roseus of a new isoform of SLS, SLS2, sharing 97 % nucleotide sequence identity with the previously characterized SLS1. We also discovered that both isoforms further oxidize secologanin into secoxyloganin. SLS2 had however a different expression profile, being the major isoform in aerial organs that constitute the main site of MIA accumulation. Unfortunately, we were unable to find a current C. roseus transcriptome database containing simultaneously well reconstructed sequences of SLS isoforms and accurate expression levels. After a pair of close mRNA encoding tabersonine 16 hydroxylase (T16H1 and T16H2), this is the second example of improperly assembled transcripts from the MIA pathway in the public transcriptome databases. To construct a more complete transcriptome resource for C. roseus, we re-processed previously published transcriptome data by combining new single assemblies. Care was particularly taken during clustering and filtering steps to remove redundant contigs but not transcripts encoding potential isoforms by monitoring quality reconstruction of MIA genes and specific SLS and T16H isoforms. The new consensus transcriptome allowed a precise estimation of abundance of SLS and T16H isoforms, similar to qPCR measurements. CONCLUSIONS: The C. roseus consensus transcriptome can now be used for characterization of new genes of the MIA pathway. Furthermore, additional isoforms of genes encoding distinct MIA biosynthetic enzymes isoforms could be predicted suggesting the existence of a higher level of complexity in the synthesis of MIA, raising the question of the evolutionary events behind what seems like redundancy. PMID- 26285574 TI - Re-evaluation of diagnostic parameters is crucial for obtaining accurate data on idiopathic pulmonary fibrosis. AB - BACKGROUND: The FinnishIPF registry is a prospective, longitudinal national registry study on the epidemiology of idiopathic pulmonary fibrosis (IPF). It was designed to describe the characteristics, management and prognosis of prevalent and incident IPF patients. The study was initiated in 2012. METHODS: We present here results limited to five university hospitals. Patients with IPF were screened from hospital registries using ICD-10 diagnosis codes J84.1 and J84.9. All patients who gave informed consent were included and evaluated using novel diagnostic criteria. Point prevalence on the 31(st) of December in 2012 was calculated using the reported population in each university hospital city as the denominator. RESULTS: Patients with ICD-10 codes J84.1 and J84.9 yielded a heterogeneous group - on the basis of patient records assessed by pulmonologists only 20-30 % of the cases were IPF. After clinical, radiological and histological re-evaluation 111 of 123 (90 %) of patients fulfilled the clinical criteria of IPF. The estimated prevalence of IPF was 8.6 cases/100 000. 60.4 % were men. Forty four percent of the patients were never-smokers. At diagnosis, the patients' mean age was 73.5 years and mean FVC was 80.4 % and DLCO 57.3 % of predicted. CONCLUSIONS: Our results suggest that hospital registries are inaccurate for epidemiological studies unless patients are carefully re evaluated. IPF is diagnosed in Finland at a stage when lung function is still quite well preserved. Smoking in patients with IPF was less common than in previous reports. PMID- 26285575 TI - Adjustment of the GRACE score by HemoglobinA1c enables a more accurate prediction of long-term major adverse cardiac events in acute coronary syndrome without diabetes undergoing percutaneous coronary intervention. AB - BACKGROUND: The Global Registry of Acute Coronary Events (GRACE) risk score is widely recommended for risk assessment in patients with acute coronary syndrome (ACS). Chronic hyperglycemia [hemoglobinA1c (HbA1c)] can independently predict major adverse cardiac events (MACEs) in patients with ACS. We investigated whether the prediction of MACEs with the GRACE score could be improved with the addition of HbA1c content in ACS patients without diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI). METHODS: We enrolled 549 ACS patients without DM who underwent PCI. The GRACE score and HbA1c content were determined on admission. Correlation was analyzed by Spearman's rank correlation. Cumulative MACE curve was calculated using the Kaplan-Meier method. Multivariate Cox regression was used to identify predictors of MACEs. Additionally, the predictive value of HbA1c content alone and combined with GRACE score was estimated by the area under the receiver-operating characteristic curve (AUC), continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: During a median of 42.3 months (interquartile range 39.3-44.2 months), 16 (2.9%) were lost to follow-up, and patients experienced 69 (12.9%) MACEs: 51 (9.6%) all-cause deaths and 18 (3.4%) nonfatal myocardial infarction cases. The GRACE score was positively associated with HbA1c content. Multivariate Cox analysis showed that both GRACE score and HbA1c content were independent predictors of MACEs (hazard ratio 1.030; 95% CI 1.020-1.040; p < 0.001; 3.530; 95% CI 1.927-6.466; p < 0.001, respectively). Furthermore, Kaplan Meier analysis demonstrated increased risk of MACEs with increasing HbA1c content (log-rank 33.906, p < 0.001). Adjustment of the GRACE risk estimate by HbA1c improved the predictive value of the GRACE score [increase in AUC from 0.75 for the GRACE score to 0.80 for the GRACE score plus HbA1c, p = 0.012; IDI = 0.055, p < 0.001; NRI (>0) = 0.70, p < 0.001]. CONCLUSIONS: HbA1c content is positively associated with GRACE risk score and their combination further improved the risk stratification for ACS patients without DM undergoing PCI. PMID- 26285577 TI - Macular hole formation following intravitreal injection of ranibizumab for branch retinal vein occlusion: a case report. AB - BACKGROUND: Macular hole formation after anti-vascular endothelial growth factor therapy is a rare complication. We report macular hole formation after intravitreal ranibizumab injection for branch retinal vein occlusion. CASE PRESENTATION: A 63-year-old Asian male was treated with intravitreal ranibizumab injection for chronic macular edema with branch retinal vein occlusion in his right eye. Before treatment, best-corrected visual acuity in his right eye was 20/200. Nine days after injection, a full thickness macular hole developed with reduction of macular edema. After pars plana vitrectomy combined with cataract surgery, the macular hole was successfully closed, and the best-corrected visual acuity in his right eye improved to 20/40. CONCLUSION: The possibility of an infrequent complication like macular hole should be considered for intravitreal ranibizumab for macular edema with branch retinal vein occlusion. PMID- 26285576 TI - Alpha7 nicotinic acetylcholine receptor is required for blood-brain barrier injury-related CNS disorders caused by Cryptococcus neoformans and HIV-1 associated comorbidity factors. AB - BACKGROUND: Cryptococcal meningitis is the most common fungal infection of the central nervous system (CNS) in HIV/AIDS. HIV-1 virotoxins (e.g., gp41) are able to induce disorders of the blood-brain barrier (BBB), which mainly consists of BMEC. Our recent study suggests that alpha7 nAChR is an essential regulator of inflammation, which contributes to regulation of NF-kappaB signaling, neuroinflammation and BBB disorders caused by microbial (e.g., HIV-1 gp120) and non-microbial [e.g., methamphetamine (METH)] factors. However, the underlying mechanisms for multiple comorbidities are unclear. METHODS: In this report, an aggravating role of alpha7 nAChR in host defense against CNS disorders caused by these comorbidities was demonstrated by chemical [inhibitor: methyllycaconitine (MLA)] and genetic (alpha7(-/-) mice) blockages of alpha7 nAChR. RESULTS: As shown in our in vivo studies, BBB injury was significantly reduced in alpha7(-/-) mice infected with C. neoformans. Stimulation by the gp41 ectodomain peptide (gp41-I90) and METH was abolished in the alpha7(-/-) animals. C. neoformans and gp41-I90 could activate NF-kappaB. Gp41-I90- and METH-induced monocyte transmigration and senescence were significantly inhibited by MLA and CAPE (caffeic acid phenethyl ester, an NF-kappaB inhibitor). CONCLUSIONS: Collectively, our data suggest that alpha7 nAChR plays a detrimental role in the host defense against C. neoformans- and HIV-1 associated comorbidity factors induced BBB injury and CNS disorders. PMID- 26285578 TI - The danger of underlying Chlamydia trachomatis infection in treating urinary tract infection with over-the-counter antibiotics. PMID- 26285579 TI - Comparative effectiveness of two different interbody fusion methods for transforaminal lumbar interbody fusion: cage versus morselized impacted bone grafts. AB - BACKGROUND: The use of an interbody fusion device (cage) to assist fusion and increase intervertebral stability is widely supported. We applied the morselized impacted bone graft method without using a cage in a single level interbody fusion with encouraging medium-term clinical results. The purpose of this paper is to compare the clinical and radiological results of local bone grafts with a cage to morselized impacted bone grafts without cage, in patients undergoing transforaminal lumbar interbody fusion (TLIF) surgery. METHODS: One hundred eighty-nine consecutive patients who underwent TLIF in our hospital were evaluated from July 2009 to July 2012. Eighty-four patients received TLIF and local bone graft with one polyetheretherketone (PEEK) cage, while 96 patients received the TLIF with local morselized impacted bone grafts without a cage. The clinical data and perioperative parameters of the patients in the two groups were recorded and compared. RESULTS: The mean follow-up time was 35 months. There were no significant differences in operation time and blood loss between the two groups. Single-level fusion was performed in all patients. There were no statistically significant differences between the two groups, according to the preoperative or postoperative Oswestry Disability Index (ODI) score. No statistically significant differences in fusion rate were observed between the two groups. At the final follow-up, the ratio of the disc height to vertebral height (HR) was not significantly different between the two groups. CONCLUSION: Morselized impacted bone graft is as beneficial as local bone grafts with a cage for TLIF. Since the no cage procedure is less expensive, the morselized impacted bone graft is an affordable choice for single level TLIF, especially in less developed regions. PMID- 26285580 TI - The influence of neighbourhood-level socioeconomic deprivation on cardiovascular disease mortality in older age: longitudinal multilevel analyses from a cohort of older British men. AB - BACKGROUND: Evidence from longitudinal studies on the influence of neighbourhood socioeconomic factors in older age on cardiovascular disease (CVD) mortality is limited. We aimed to investigate the prospective association of neighbourhood level deprivation in later life with CVD mortality, and assess the underlying role of established cardiovascular risk factors. METHODS: A socially representative cohort of 3924 men, aged 60-79 years in 1998-2000, from 24 British towns, was followed up until 2012 for CVD mortality. Quintiles of the national Index of Multiple Deprivation (IMD), a composite score of neighbourhood-level factors (including income, employment, education, housing and living environment) were used. Multilevel logistic regression with discrete-time models (stratifying follow-up time into months) were used. RESULTS: Over 12 years, 1545 deaths occurred, including 580 from CVD. The risk of CVD mortality showed a graded increase from IMD quintile 1 (least deprived) to 5 (most deprived). Compared to quintile 1, the age-adjusted odds of CVD mortality in quintile 5 were 1.71 (95% CI 1.32 to 2.21), and 1.62 (95% CI 1.23 to 2.13) on further adjustment for individual social class, which was attenuated slightly to 1.44 (95% CI 1.09 to 1.89), but remained statistically significant after adjustment for smoking, body mass index, physical activity and use of alcohol. Further adjustment for blood pressure, high-density lipoprotein cholesterol and prevalent diabetes made little difference. CONCLUSIONS: Neighbourhood-level deprivation was associated with an increased risk of CVD mortality in older people independent of individual-level social class and cardiovascular risk factors. The role of other specific neighbourhood-level factors merits further research. PMID- 26285581 TI - Correlates of sitting time in adults with type 2 diabetes. AB - BACKGROUND: Studies suggest a relationship between sitting time and cardiovascular disease mortality. Our aim was to identify socio-demographic, contextual, and clinical (e.g., body composition, diabetes duration) correlates of self-reported sitting time among adults with type 2 diabetes, a clinical population at high risk for cardiovascular disease. We sought to determine if there was an inverse relationship between sitting and step counts in a diabetes cohort in whom we had previously identified low step counts with further lowering in fall/winter. METHODS: The cohort included 198 adults (54 % men; age 60.0 SD 11.5 years; Body mass index 30.4 SD 5.6 kg/m(2)) (Montreal, Canada). Socio demographic, contextual and clinical factors were assessed using standardized questionnaires and step counts with a pedometer over 14 days (concealed viewing windows). Total sitting time was estimated once per season (up to 4 times per year at -month intervals) using the International Physical Activity Questionnaire Short version. Potential sitting time correlates were evaluated using Bayesian longitudinal hierarchical linear regression models in participants with sitting time data (n = 191). RESULTS: The average sitting time was 308 (SD 161) minutes/day without variation across seasons. Sitting time correlates were being an immigrant (56 fewer minutes/day spent sitting compared to non- immigrants, 95 % credible interval, CrI: -100, -11) and having a university degree (55 more minutes/day spent sitting compared to those without a university degree, 95 % CrI: 10, 100) after adjustment for potential correlates observed in univariate analyses (sex, age, job status, waist circumference, depressed mood, steps). Correlation between sitting and steps, adjusted for age and sex, was -0.144 (95 % CI: -0.280, 0.002). CONCLUSION: There was low correlation between sitting time and step counts. Therefore, high sitting time and low step counts are behaviours that may need to be independently targeted. Interventions to reduce sitting time in adults with type 2 diabetes may need to target non-immigrants and those with a university degree. PMID- 26285582 TI - Factors influencing uptake of contraceptive implants in the immediate postpartum period among HIV infected and uninfected women at two Kenyan District Hospitals. AB - BACKGROUND: Family planning is a cost effective strategy for prevention of mother to child transmission of HIV and reduction of maternal/infant morbidity and mortality. Contraceptive implants are a safe, effective, long term and reversible family planning method whose use remains low in Kenya. We therefore set out to determine and compare the uptake, and factors influencing uptake of immediate postpartum contraceptive implants among HIV infected and uninfected women at two hospitals in Kenya. METHODS: This cross sectional study targeted postpartum mothers at two Kenyan district hospitals (one urban and one rural). All participants received general family planning and method specific (Implant) counseling followed by immediate insertion of contraceptive implants to those who consented. The data was analyzed by descriptive analysis, T-test, Chi square tests and logistic regression. RESULTS: One hundred eighty-five participants were enrolled (91 HIV positive and 94 HIV negative) with a mean age of 26 years. HIV positive mothers were significantly older (27.5 years) than their HIV negative counterparts (24.5 years), P = 0.001. The two groups were comparable in education, employment, marital status and religious affiliation. Overall, the uptake of contraceptive implants in the immediate postpartum period was 50.3% and higher among HIV negative than HIV positive participants (57% vs. 43%, P = 0.046). Multivariate analysis revealed that a negative HIV status (P = 0.017) and prior knowledge of contraceptive implants (P = 0.001) were independently associated with increased uptake of contraceptive implants. CONCLUSION: There was a high uptake of immediate postpartum contraceptive implants among both HIV infected and un-infected women; efforts therefore need to be made in promoting this method of family planning in Kenya and providing this method to women in the immediate postpartum period so as to utilize this critical opportunity to increase uptake and reduce the high unmet need for family planning. PMID- 26285583 TI - GPs should consider delaying prescription of antibiotics, says NICE. PMID- 26285584 TI - The Primary Glucose-Lowering Effect of Metformin Resides in the Gut, Not the Circulation: Results From Short-term Pharmacokinetic and 12-Week Dose-Ranging Studies. AB - OBJECTIVE: Delayed-release metformin (Met DR) is formulated to deliver the drug to the lower bowel to leverage the gut-based mechanisms of metformin action with lower plasma exposure. Met DR was assessed in two studies. Study 1 compared the bioavailability of single daily doses of Met DR to currently available immediate release metformin (Met IR) and extended-release metformin (Met XR) in otherwise healthy volunteers. Study 2 assessed glycemic control in subjects with type 2 diabetes (T2DM) over 12 weeks. RESEARCH DESIGN AND METHODS: Study 1 was a phase 1, randomized, four-period crossover study in 20 subjects. Study 2 was a 12-week, phase 2, multicenter, placebo-controlled, dose-ranging study in 240 subjects with T2DM randomized to receive Met DR 600, 800, or 1,000 mg administered once daily; blinded placebo; or unblinded Met XR 1,000 or 2,000 mg (reference). RESULTS: The bioavailability of 1,000 mg Met DR b.i.d. was ~50% that of Met IR and Met XR (study 1). In study 2, 600, 800, and 1,000 mg Met DR q.d. produced statistically significant, clinically relevant, and sustained reductions in fasting plasma glucose (FPG) levels over 12 weeks compared with placebo, with an ~40% increase in potency compared with Met XR. The placebo-subtracted changes from baseline in HbA1c level at 12 weeks were consistent with changes in FPG levels. All treatments were generally well tolerated, and adverse events were consistent with Glucophage/Glucophage XR prescribing information. CONCLUSIONS: Dissociation of the glycemic effect from plasma exposure with gut-restricted Met DR provides strong evidence for a predominantly lower bowel-mediated mechanism of metformin action. PMID- 26285585 TI - Stroke patients admitted within normal working hours are more likely to achieve process standards and to have better outcomes. AB - BACKGROUND: The presence of a 'weekend' effect has been shown across a range of medical conditions, but has not been consistently observed for patients with stroke. AIMS: We investigated the impact of admission time on a range of process and outcome measures after stroke. METHODS: Using routine data from National Scottish data sets (2005-2013), time of admission was categorised into weekday, weeknight and weekend/public holidays. The main process measures were swallow screen on day of admission (day 0), brain scan (day 0 or 1), aspirin (day 0 or 1), admission to stroke unit (day 0 or 1), and thrombolysis administration. After case-mix adjustment, multivariable logistic regression was used to estimate the OR for mortality and discharge to home/usual place of residence. RESULTS: There were 52,276 index stroke events. Compared to weekday, the adjusted OR (95%CI) for early stroke unit admission was 0.81 (0.77 to 0.85) for weeknight admissions and 0.64 (0.61 to 0.67) for weekend/holiday admissions; early brain scan 1.30 (0.87 to 1.94) and 1.43 (0.95 to 2.18); same day swallow screen 0.86 (0.81 to 0.91) and 0.85 (0.81 to 0.90); thrombolysis 0.85 (0.75 to 0.97) and 0.85 (0.75 to 0.97), respectively. Seven-day mortality, 30-day mortality and 30-day discharge for weekend admission compared to weekday was 1.17 (1.05 to 1.30); 1.08 (1.00 to 1.17); and 0.90 (0.85 to 0.95), respectively. CONCLUSIONS: Patients with stroke admitted out of hours and at weekends or public holidays are less likely to be managed according to current guidelines. They experience poorer short-term outcomes than those admitted during normal working hours, after correcting for known independent predictors of outcome and early mortality. PMID- 26285586 TI - Management of spontaneous intracranial hypotension - Transorbital ultrasound as discriminator. AB - OBJECTIVE: Spontaneous intracranial hypotension (SIH) is most commonly caused by cerebrospinal fluid (CSF) leakage. Therefore, we hypothesised that patients with orthostatic headache (OH) would show decreased optic nerve sheath diameter (ONSD) during changes from supine to upright position. METHODS: Transorbital B-mode ultrasound was performed employing a high-frequency transducer for ONSD measurements in the supine and upright positions. Absolute values and changes of ONSD from supine to upright were assessed. Ultrasound was performed in 39 SIH patients, 18 with OH and 21 without OH, and in 39 age-matched control subjects. The control group comprised 20 patients admitted for back surgery without headache or any orthostatic symptoms, and 19 healthy controls. RESULTS: In supine position, mean ONSD (+/-SD) was similar in patients with (5.38+/-0.91 mm) or without OH (5.48+/-0.89 mm; p=0.921). However, in upright position, mean ONSD was different between patients with (4.84+/-0.99 mm) and without OH (5.53+/-0.99 mm; p=0.044). Furthermore, the change in ONSD from supine to upright position was significantly greater in SIH patients with OH (-0.53+/-0.34 mm) than in SIH patients without OH (0.05+/-0.41 mm; p<=0.001) or in control subjects (0.01+/ 0.38 mm; p<=0.001; area under the curve: 0.874 in receiver operating characteristics analysis). CONCLUSIONS: Symptomatic patients with SIH showed a significant decrease of ONSD, as assessed by ultrasound, when changing from the supine to the upright position. Ultrasound assessment of the ONSD in two positions may be a novel, non-invasive tool for the diagnosis and follow-up of SIH and for elucidating the pathophysiology of SIH. PMID- 26285587 TI - Direct oral anticoagulants (DOACs). AB - DOACs are a new group of blood-thinner medications that may have some advantages over warfarin. A health care provider will look at several different factors to help patients decide if a DOAC is a good choice. Patients taking DOACs should discuss medication changes, a plan for taking the DOAC before and after a surgery, and any bleeding side effects with their health care provider. PMID- 26285588 TI - Vascular function and brain-derived neurotrophic factor: The functional capacity factor. AB - Brain-derived neurotrophic factor (BDNF) is essential for neurocognitive function. This study aims at establishing a plausible link between level of serum BDNF, functional capacity (FC), and vascular function in 181 young (age 25.5+/ 9.1 years old), apparently healthy adults. Fasting blood samples were drawn from participants' antecubital veins into plain glass tubes while they were in a sitting position to evaluate serum BDNF using enzyme-linked immunosorbent assay (ELISA). Mercury-in-silastic strain-gauge plethysmography was used to determine arterial function indices, blood flow and vascular resistance at rest and following 5 minutes of arterial ischemia. The 6-minute walk distance (6MWD) test was used to determine FC, according to the American Thoracic Society Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories guidelines. It was conducted in an enclosed corridor on a flat surface with a circular track 33 meters long. The walking course was demarcated with bright colored cones. The 6MWD correlated with BDNF (r=0.3, p=0.000), as well as with forearm blood inflow (r=0.5, p=0.000) and vascular resistance (r = -0.4, p=0.000). Subsequent comparison showed that BDNF and blood inflow were greater (p<0.05) while vascular resistance was less (p<0.05) in participants who achieved a longer 6MWD. Similarly, BDNF correlated with forearm blood inflow (r=0.4, p=0.000) and vascular resistance (r = -0.4, p=0.000). Subsequent comparison showed improved vascular function (p<0.05) in the participants with greater BDNF. In conclusion, these findings might suggest that improved vascular function in individuals with greater FC is mediated, at least partially, by an enhanced serum BDNF level. PMID- 26285589 TI - Images in Vascular Medicine. Carotidynia. PMID- 26285590 TI - Advances in axial imaging of peripheral vascular disease. AB - Peripheral artery disease (PAD) has become increasingly common in the US patient population and can be a highly symptomatic and significant source of morbidity. When PAD is suspected, the first-line screening study that is obtained is typically a noninvasive evaluation that includes the ankle brachial index (ABI). Following a positive screening study, invasive catheter digital subtraction angiography (DSA) has been historically used to image the peripheral artery system and still remains the gold standard. However, newer developments in axial imaging including computed tomography angiography (CTA) and magnetic resonance angiography (MRA) have in large part supplanted DSA for imaging the peripheral artery system in clinical practice. Benefits of CTA include rapid noninvasive acquisition, wide availability, high spatial resolution, and the ability to generate isotropic datasets on 64-detector row and higher CT scanners, thereby allowing for multiplanar 3D reformatting. Drawbacks of CTA include the exposure to both iodinated contrast and ionizing radiation, although the radiation dose exposure is lower than for DSA, and newer techniques such as using low tube voltage and rapid acquisition times allow for lower contrast doses. The presence of vascular calcification also limits the evaluation of small distal arteries using CTA, although the development of dual-energy CT techniques has significantly addressed this issue. Benefits of MRA include the avoidance of exposure to ionizing radiation and high diagnostic accuracy, while drawbacks include limited availability and increased cost along with the risk of nephrogenic systemic fibrosis that is associated with gadolinium-based contrast agents, although the latter can be mitigated by using newer non-contrast MR angiography techniques. Future technical advances in CT and MR hardware and software and MR pulse sequences will likely lead to the broader applicability and increased accuracy of noninvasive axial imaging in the evaluation of patients with peripheral artery disease. PMID- 26285591 TI - The relationship between body temperature, heart rate, breathing rate, and rate of oxygen consumption, in the tegu lizard (Tupinambis merianae) at various levels of activity. AB - The present study determined whether EEG and/or EMG recordings could be used to reliably define activity states in the Brazilian black and white tegu lizard (Tupinambis merianae) and then examined the interactive effects of temperature and activity states on strategies for matching O2 supply and demand. In a first series of experiments, the rate of oxygen consumption (VO2), breathing frequency (fR), heart rate (fH), and EEG and EMG (neck muscle) activity were measured in different sleep/wake states (sleeping, awake but quiet, alert, or moving). In general, metabolic and cardio-respiratory changes were better indictors of the transition from sleep to wake than were changes in the EEG and EMG. In a second series of experiments, the interactive effects of temperature (17, 27 and 37 degrees C) and activity states on fR, tidal volume (VT), the fraction of oxygen extracted from the lung per breath (FIO2-FEO2), fH, and the cardiac O2 pulse were quantified to determine the relative roles of each of these variables in accommodating changes in VO2. The increases in oxygen supply to meet temperature- and activity-induced increases in oxygen demand were produced almost exclusively by increases in fH and fR. Regression analysis showed that the effects of temperature and activity state on the relationships between fH, fR and VO2 was to extend a common relationship along a single curve, rather than separate relationships for each metabolic state. For these lizards, the predictive powers of fR and fH were maximized when the effects of changes in temperature, digestive state and activity were pooled. However, the best r(2) values obtained were 0.63 and 0.74 using fR and fH as predictors of metabolic rate, respectively. PMID- 26285592 TI - Biochemical effects of mutations in the gene encoding the alpha subunit of eukaryotic initiation factor (eIF) 2B associated with Vanishing White Matter disease. AB - BACKGROUND: Leukoencephalopathy with Vanishing White Matter (VWM) is an autosomal recessive disorder caused by germline mutations in the genes EIF2B1-5, which encode the 5 subunits of the eukaryotic translation initiation factor eIF2B. To date, analysis of the biochemical effects of mutations in the EIF2B2-5 genes has been carried out, but no study has been performed on mutations in the EIF2B1 gene. This gene encodes eIF2Balpha, the smallest subunit in eIF2B which has an important role in both the structure and regulation of the eIF2B complex. METHODS: eIF2B subunits were overexpressed in HEK293 cells and isolated from the resulting cell lysates by affinity chromatography. Formation of the eIF2B complex and binding of its substrate, eIF2, was assessed by western blot. Assays of the guanine nucleotide exchange (GEF) activity were also carried out. RESULTS: Of the 5 eIF2Balpha mutations studied, we found 3 that showed loss or reduction of binding of eIF2Balpha to the rest of the complex, one with increased GEF activity, and one where no effects on activity or complex formation were observed. CONCLUSIONS: This is the first study on eIF2Balpha VWM mutations. We show that some mutations cause expected decreases in GEF activity or complex formation, similar to a majority of observed VWM mutations. However, we also observe some unexpected changes which hint at other effects of these mutations on as yet undescribed functions of eIF2B. PMID- 26285595 TI - Research Priorities in Correctional Nursing Practice: Results of a Three-Round Delphi Study. AB - Correctional nursing has been recognized as a specialty since 1985, but research to describe and support nursing practice in the criminal justice system has been sparse. The development of a research agenda can stimulate the research necessary to provide an evidence base for specialty practice development. A three-round Delphi study was undertaken to elicit a prioritized list of research topics to guide future research efforts for meaningful results. Six predominant themes emerged from an analysis of top research questions generated by a panel of 18 correctional nursing experts. Research priorities include critical thinking and clinical judgment, competency and educational level, assessment, nursing protocols, effect on patient outcomes, and the environment of care. PMID- 26285594 TI - Alcohol Production, Prevention Strategies, and Inmate Knowledge About the Risk for Botulism From Pruno Consumption in a Correctional Facility--Arizona, 2013. AB - During July to November 2012, two botulism outbreaks (12 cases total) occurred in one all-male prison; both were associated with illicitly brewed alcohol (pruno) consumption. Inmate surveys were conducted to evaluate and develop prevention and education strategies. Qualitative surveys with open-ended questions were performed among inmates from rooms where outbreaks occurred to learn about pruno consumption. Quantitative surveys assessed knowledge gained after the outbreaks and preferred information sources. For the quantitative surveys, 250 inmates were randomly selected by bed from across the correctional facility and 164 inmates were interviewed. Only 24% of inmates reported any botulism knowledge before the outbreaks and education outreach, whereas 73% reported knowledge after the outbreaks (p < .01). Preferred information sources included handouts/fliers (52%) and the prison television channel (32%). PMID- 26285593 TI - Outcomes of endoscopic management of primary and refractory postcholecystectomy biliary leaks in a multicentre review of 178 patients. AB - BACKGROUND: Biliary leaks have been treated with endoscopic management using different techniques with conflicting results. Furthermore the appropriate rescue therapy for refractory leaks has not been established. We evaluated the clinical effectiveness of initial endotherapy for postcholecystectomy biliary leaks using an homogenous approach (sphincterotomy + placement of a 10-French plastic stent) in a large series of patients as well as the optimal and efficacy of rescue endotherapy for refractory biliary leaks. METHODS: This was a multicenter, retrospective study of 178 patients who underwent endoscopic management of postcholecystectomy biliary leaks with a combination of biliary sphincterotomy and the placement of a large-bore (10-French) plastic stent. Data were collected to analyze the clinical outcomes and technical success, efficacy of the rescue endotherapy and the need for surgery, adverse events and prognostic factors for clinical success of endotherapy. RESULTS: Following endotherapy, closure of the leak was accomplished in 162/178 patients (91.0%). The multivariate logistic model showed that the type of leak, namely a high-grade biliary leak, was the only independent prognostic factor associated with treatment failure (OR = 26.78; 95% CI = 6.59-108.83; P < 0.01). The remaining 16 patients were treated with multiple plastic stents (MPSs) with a success rate of 62.5% (10 patients). The use of fewer than 3 plastic stents (P = 0.023) and a high-grade biliary leak (P = 0.034) were shown to be significant predictors of treatment failure with MPSs in refractory bile leaks. The 6 patients in whom the placement of MPSs failed were retreated with a fully cover self-expandable metallic stent (FCSEMS), resulting in closure of the leak in all cases. CONCLUSIONS: Endotherapy of biliary leaks with a combination of biliary sphincterotomy and the placement of a large-bore plastic stent is associated with a high rate of success (90%). However in our series there were several failures using MPSs as a strategy for rescue endotherapy suggesting that refractory biliary leaks should be treated with FCSEMS especially in patients with high-grade leaks. PMID- 26285598 TI - Timing of surgery in infective endocarditis. AB - Although early surgery is performed in approximately half of patients for the treatment of infective endocarditis (IE), the optimal timing of surgery remains unclear. Appropriate early surgery can avoid death and severe complications, but nearly one-quarter of patients with indications for surgery do not receive surgical intervention. Multidisciplinary collaborations among cardiologists, cardiac surgeons and infectious disease specialists are required for appropriate decisions about indication and timing of surgical intervention. Moreover, the potential benefits of early surgery should be weighed against its operative risks and long-term consequences. The main indications for early surgery in patients with IE are heart failure (HF), uncontrolled infection and prevention of embolism. Role of early surgery has been expanding and a recent randomised trial demonstrated that early surgery performed within 48 h after the diagnosis of IE effectively reduced systemic embolisms without increasing operative mortality or recurrence of IE. Urgent surgery is indicated in patients who have moderate to severe HF, uncontrolled infection and large vegetations associated with severe valvular disease. However, surgery should be delayed for 2-4 weeks in patients with large cerebral infarction and for at least 4 weeks in those with intracerebral haemorrhage if possible, because early surgery may pose significant risks of neurological deterioration and perioperative cerebral bleeding. The decision for surgical timing should be based on individual risk-benefit analysis, and early surgery is strongly indicated if its benefits exceed operative risks. PMID- 26285597 TI - Comparison of Opt-In Versus Opt-Out Testing for Sexually Transmitted Infections Among Inmates in a County Jail. AB - A majority of jails in the United States rely on an opt-in (voluntary) rather than opt-out (universal) approach to testing for sexually transmitted infections (STIs). This study compares an opt-out approach at intake to opt-in testing during incarceration and estimates the prevalence of common STIs among jail inmates. Data derive from a universal intake pilot testing program (n = 298) and an established, student-led voluntary testing program (n = 1,963), respectively. The adjusted prevalence as well as the odds of testing positive for chlamydia were significantly higher in the opt-out program (p = .025 and .008, respectively) than the opt-in program but not for gonorrhea (p = .402 and .300, respectively). These results demonstrate the potential public health benefit of implementation of universal STI testing of jail inmates. PMID- 26285599 TI - True and true, but not a paradox. PMID- 26285600 TI - Riociguat for pulmonary hypertension in congenital heart disease: opportunities and challenges. PMID- 26285601 TI - Dear Readers of Scandinavian Journal of Immunology and ECI2015 Attendees. PMID- 26285602 TI - Clinical Management of Acute Portal/Mesenteric Vein Thrombosis. AB - BACKGROUND: Acute thrombosis of the portal vein (PV) and/or the mesenteric vein (MV) is a rare but potentially life-threatening disease. A multitude of risk factors for acute portal vein thrombosis (PVT)/mesenteric vein thrombosis (MVT) have been identified, including liver cirrhosis, malignancy, coagulation disorders, intra-abdominal infection/inflammation, and postoperative condition. METHODS: This article analyses the treatment options for acute PVT/MVT. RESULTS: Initially, the clinical management should identify patients with an intra abdominal focus requiring immediate surgical intervention (e.g. bowel ischaemia). Subsequently, emphasis is placed on the recanalization of the PV/MV or at least the prevention of thrombus extension to avoid long-term complications of portal hypertension. Several therapeutic options are currently available, including anticoagulation therapy, local/systemic thrombolysis, interventional or surgical thrombectomy, and a combination of these procedures. Due to the lack of prospective randomized studies, a comparison between these therapeutic approaches regarding the efficacy of PV/MV recanalization is difficult, if not impossible. CONCLUSION: In patients with acute PVT/MVT, an individualized treatment based on the clinical presentation, the underlying disease, the extent of the thrombosis, and the patients' comorbidities is mandatory. Therefore, these patients should be considered for an interdisciplinary therapy in specialized centres with the option to utilise all therapeutic approaches currently available. PMID- 26285603 TI - Modification of starch metabolism in transgenic Arabidopsis thaliana increases plant biomass and triples oilseed production. AB - We have identified a novel means to achieve substantially increased vegetative biomass and oilseed production in the model plant Arabidopsis thaliana. Endogenous isoforms of starch branching enzyme (SBE) were substituted by either one of the endosperm-expressed maize (Zea mays L.) branching isozymes, ZmSBEI or ZmSBEIIb. Transformants were compared with the starch-free background and with the wild-type plants. Each of the maize-derived SBEs restored starch biosynthesis but both morphology and structure of starch particles were altered. Altered starch metabolism in the transformants is associated with enhanced biomass formation and more-than-trebled oilseed production while maintaining seed oil quality. Enhanced oilseed production is primarily due to an increased number of siliques per plant whereas oil content and seed number per silique are essentially unchanged or even modestly decreased. Introduction of cereal starch branching isozymes into oilseed plants represents a potentially useful strategy to increase biomass and oilseed production in related crops and manipulate the structure and properties of leaf starch. PMID- 26285604 TI - Association of metabolic parameters and rs726344 in FNDC5 with serum irisin concentrations. AB - BACKGROUND/OBJECTIVES: Irisin has been suggested as a novel myokine with beneficial effects in rodents. However, previous data in humans showed conflicting results regarding its association with metabolic phenotypes and regulation of secretion. Furthermore, although an association of rs726344 in FNDC5 (fibronectin type III domain containing 5) coding for irisin with insulin sensitivity was reported, the effects of genetic variation at this locus on irisin serum levels have not been investigated, so far. Therefore, we investigated circulating irisin and the associations with rs726344 in a cohort of >1000 subjects. SUBJECTS/METHODS: Irisin serum concentrations were measured with enzyme-linked immunosorbent assay. Associations with metabolic parameters including renal function, glucose and lipid metabolism, inflammation, as well as adipokine profiles, were assessed in regression models. Dynamic changes of serum irisin were investigated during oral glucose tolerance test (OGTT) in a subset of the cohort (n=136). rs726344 was genotyped in all subjects and analyzed for associations with serum irisin and traits of the metabolic syndrome. RESULTS: Irisin was negatively associated with fat mass, fasting glucose and dyslipidemia but not with other adipokines. Moreover, irisin decreased during an OGTT in a subcohort comprising subjects with normal glucose tolerance, impaired fasting glucose, impaired glucose tolerance and type 2 diabetes mellitus. rs726344 was not associated with serum irisin levels or with other anthropometric and biochemical parameters. CONCLUSIONS: Circulating irisin levels are associated with a beneficial metabolic profile but not with other adipokines and not with rs726344 in our cohort. Our data suggest a potential favorable role of irisin in the regulation of metabolism. PMID- 26285605 TI - The bigger, the stronger? Insights from muscle architecture and nervous characteristics in obese adolescent girls. AB - BACKGROUND: Young obese youth are generally stronger than lean youth. This has been linked to the loading effect of excess body mass, acting as a training stimulus comparable to strength training. Whether this triggers specific adaptations of the muscle architecture (MA) and voluntary activation (VA) that could account for the higher strength of obese subjects remains unknown. METHODS: MA characteristics (that is, pennation angle (PA), fascicle length (FL) and muscle thickness (MT)) and muscle size (that is, anatomical cross-sectional area (ACSA)) of the knee extensor (KE) and plantar flexor (PF) muscles were evaluated in 12 obese and 12 non-obese adolescent girls (12-15 years). Maximal isometric torque and VA of the KE and PF muscles were also assessed. RESULTS: Results revealed higher PA (P<0.05), greater MT (P<0.001), ACSA (P<0.01), segmental lean mass (P<0.001) and VA (P<0.001) for KE and PF muscles in obese girls. Moreover, obese individuals produced a higher absolute torque than their lean counterparts on the KE (224.6+/-39.5 vs 135.7+/-32.7 N m, respectively; P<0.001) and PF muscles (73.3+/-16.5 vs 44.5+/-6.2 N m; P<0.001). Maximal voluntary contraction (MVC) was correlated to PA for the KE (r=0.46-0.57, P<0.05-0.01) and PF muscles (r=0.45-0.55, P<0.05-0.01). MVC was also correlated with VA (KE: r=0.44, P<0.05; PF: r=0.65, P<0.001) and segmental lean mass (KE: r=0.48, P<0.05; PF: r=0.57, P<0.01). CONCLUSIONS: This study highlighted favorable muscular and nervous adaptations to obesity that account for the higher strength of obese youth. The excess of body mass supported during daily activities could act as a chronic training stimulus responsible for these adaptations. PMID- 26285607 TI - Primary RET-mutated lung neuroendocrine carcinoma in MEN2B: response to RET targeted therapy. PMID- 26285606 TI - Androgen receptor and prostate cancer stem cells: biological mechanisms and clinical implications. AB - Prostate cancer (PCa) contains phenotypically and functionally distinct cells, and this cellular heterogeneity poses clinical challenges as the distinct cell types likely respond differently to various therapies. Clonal evolution, driven by genetic instability, and intraclonal cancer cell diversification, driven by cancer stem cells (CSCs), together create tumor cell heterogeneity. In this review, we first discuss PCa stem cells (PCSCs) and heterogeneity of androgen receptor (AR) expression in primary, metastatic, and treatment-failed PCa. Based on literature reports and our own studies, we hypothesize that, whereas PCSCs in primary and untreated tumors and models are mainly AR(-), PCSCs in CRPCs could be either AR(+) or AR(-/lo). We illustrate the potential mechanisms AR(+) and AR(-) PCSCs may employ to propagate PCa at the population level, mediate therapy resistance, and metastasize. As a result, targeting AR alone may not achieve long lasting therapeutic efficacy. Elucidating the roles of AR and PCSCs should provide important clues to designing novel personalized combinatorial therapeutic protocols targeting both AR(+) and AR(-) PCa cells. PMID- 26285609 TI - Assessment of Air Pollution Effects on the Respiratory System Based on Pulmonary Function Tests Performed During Spirometry Days. AB - The Polish Spirometry Day is an initiative aimed at increasing awareness of the causes, symptoms, course, and effects that accompany respiratory diseases, especially asthma and chronic obstructive pulmonary disease (COPD). In 2013, the second edition of the Spirometry Day was held. It gathered 180 medical centers and other institution. The final analysis encompassed a total of 1187 persons from 26 different locations, including rural areas, and smaller and larger city agglomerations. Of this total, 755 persons (63.6 %) completed their spirometry tests for the first time in life. Each person fulfilled a questionnaire regarding the personal information, respiratory diseases, symptoms, lifestyle, and a place of residence. In the total group, 234 (19.7 %) cases of bronchial obstruction were diagnosed. A hundred and thirty four persons with obstruction, among those tested for the first time in life (17.8 %), were unaware of their disease. The lowest values of FEV1 and FEF(1)/FVC, corresponding to the highest percentage of persons with obstruction (27.9 %) were observed in small and medium cities (100,000-500,000 inhabitants). There were differences in the prevalence of obstruction depending on the distance of the place of residence from a busy traffic road. A significant decrease of both spirometric variables was observed among people living in cities above 100,000 inhabitants within a distance lower than 50 m from roads. In general, better spirometry results were observed among inhabitants living more than 150 m from main roads. PMID- 26285608 TI - Amide-linked Ethanolamine Conjugate of Gemfibrozil as a Profound HDL Enhancer: Design, Synthesis, Pharmacological Screening and Docking Study. AB - Elevated concentration of any or all types of lipids in the plasma including hypertriglyceridemia and hypercholesterolemia leads to atherosclerotic cardiovascular disease. Effective medication needs multiple drug therapy as recommended cholesterol and triglyceride levels are difficult to achieve by monotherapy and frequently require the use of more than one lipid-lowering medication. Gemfibrozil lowers plasma triglyceride-rich lipoproteins mainly VLDL and increases HDL. It is associated with short plasma half-life (1.5h) and GIT distress on long term use. In a study it was found that ethanolamine decreases serum cholesterol, especially VLDL cholesterol and LDL cholesterol in rats fed an HF/HC diet. In the present work, we thought of exploring the effect of co-drug of gemfibrozil with ethanolamine (GE-I) as a potential combination therapy for the management of mixed hyperlipidemia. Synthesis of GE-I was effected by CDI coupling. Structure was confirmed spectrally. Interestingly kinetic studies revealed that GE-I resisted chemical and enzymatic hydrolysis. In tritoninduced hyperlipidemia, significant lowering of serum lipid levels was observed. The hallmark of GEI was its profound effect on HDL level which was raised above the normal level by 15%. Docking study also supported modulatory effect of GE-I (docking score -7.012) on PPAR-alpha which was comparable to docking score of gemfibrozil (-9.432). These preliminary observations prompt us to consider GE-I as a novel, serendipitous, hybrid anti-hyperlipidemic new chemical entity which needs be studied extensively to prove it as an HDL enhancing anti-hyperlipidemic agent. PMID- 26285610 TI - Causes of Chronic Cough in Non-smoking Patients. AB - Chronic cough is a common medical problem. The aim of the study was to analyze chronic cough causes in non-smoking patients and to search for demographic factors associated with different cough reasons. The etiology of cough was determined by medical history, diagnostic tests and response to specific treatment. Patients with significant abnormalities in the chest radiograph or spirometry were not included. The study included 131 non-smoking patients; median age 54 years, 77 % female. The most frequent causes of cough were gastroesophageal reflux disease (GERD) (62 %) and upper airway cough syndrome (UACS) (46 %). Cough variant asthma and non-asthmatic eosinophilic bronchitis (NAEB) were diagnosed in 32 (25 %) and 19 (15 %) patients, respectively. Other cough causes were found in 27 patients (21 %). Asthma was a significantly more common cause of chronic cough in women than in men (31 % vs. 3 %, p = 0.005). A reverse relationship was demonstrated for UACS (39 % vs. 67 %, p = 0.01). Patients with chronic cough aged >50 yrs were more likely to be diagnosed with less common cough causes. In conclusion, the most common chronic cough reasons are GERD and UACS. Asthma-related cough is diagnosed more frequently in females, while UACS-related cough is more frequent in males. PMID- 26285611 TI - Gastroesophageal Reflux Disease in Children with Cystic Fibrosis. AB - Previously published studies have indicated that gastroesophageal reflux (GER) disease is common in pediatric patients with cystic fibrosis. The aim of the present study was to get insight into the incidence of GER and to characterize the nature of reflux episodes in children with cystic fibrosis. This was a multicenter, prospective study of children with cystic fibrosis older than 18 months. Forty four consecutive patients (22 boys, mean age 10.4 +/- 3.6, range 3.0-17.8 years) were enrolled into the study. All patients underwent 24 h pH impedance monitoring. GER were classified according to the widely recognized criteria as an acid, weakly acid, weakly alkaline, or proximal. The pH-impedance trace was considered abnormal when acid exposure was >6 %. GER was diagnosed in 24/44 (54.5 %) children. A total of 1585 (median 35, range 7-128) reflux episodes were detected; 1199 (75.6 %) were acidic, 382 (24.1 %) weakly acidic, and 4 (0.3 %) weakly alkaline. Six hundred and ninety-one (43.6 %) reflux episodes reached the proximal esophagus. In 14/44 patients typical GER symptoms were present. We conclude that the incidence of GER in children with cystic fibrosis is very high. In the majority of patients typical GER symptoms are absent. Therefore, diagnostic procedures should be considered, regardless of lacking symptoms. Although acid reflux episodes predominate in children with cystic fibrosis, classical pH-metry may not constitute a sufficient diagnostic method in this population because of a relatively high number of proximal reflux episodes. Such episodes also indicate an increased risk for aspiration. The pH-impedance diagnostic measurement is advocated when suspecting GER in children with cystic fibrosis. PMID- 26285612 TI - Usage of Over-the-Counter and Herbal Products in Common Cold in Poland: Findings from Consumer Survey. AB - Upper respiratory tract infections are usually self-treated with synthetic and herbal over-the-counter products. The aim of the study was to assess the reasons for the purchase of those medications in Poland. We examined 413 adults, aged 18 and over (70.5% of them were women) using a questionnaire. The findings demonstrate that oral synthetic products were used by 76% of respondents, while herbal products by 30%. Synthetic products were used mainly by educated people under 65 years of age, students, and the employed. Herbal products were used mainly by older people. In conclusion, synthetic products against common cold are perceived as more effective. Such medications are used by people who probably would like to recover and return to professional activity as quickly as possible. As they generally use more medications, they are at increased risk of adverse effects resulting from drug interactions, and they should be a target group for health education programs. PMID- 26285613 TI - The Influence of Asthma Exacerbations on Health-Related Quality of Life. AB - The purpose of this study was to determine the influence of asthma on the quality of life (QoL) of patients hospitalized for an exacerbation of the disease and those with controlled asthma receiving outpatient treatment, and to establish the patients' somatic status and the level of health care utilization. This study involved 239 adults with asthma (123 hospitalized patients and 116 outpatients of family physicians). The authors used: WHOQOL-BREF questionnaire and a questionnaire measuring health care utilization. There were no differences in QoL levels between the patients with severe and controlled asthma. The psychological domain was assessed higher by hospitalized patients (p = 0.02). QoL levels correlated negatively with age, place of residence, and marital status, and positively with education. The general QoL level was most strongly influenced by gender, age, education, the number of home visits and interventions of a district nurse, and the somatic index (p < 0.05). Somatic symptoms were more severe in hospitalized patients. The QoL assessment of asthma patients in relation to somatic symptoms, health care services and socio-demographic variables allows better understanding of the complex health situation of patients at various stages of the disease, and tailoring the therapy to individual needs. Patients receiving outpatient treatment require professional psychotherapeutic support. PMID- 26285615 TI - Obinutuzumab in chronic lymphocytic leukemia. AB - Obinutuzumab is the second next-generation monoclonal anti-CD20 antibody (after ofatumumab) to enter clinical practice in chronic lymphocytic leukemia. Its superiority in association with chlorambucil as compared with chlorambucil alone has led to its approval as a first-line treatment for chronic lymphocytic leukemia, for patients who are not candidates for a more intensive treatment. PMID- 26285614 TI - Developing renal allograft surveillance strategies - urinary biomarkers of cellular rejection. AB - PURPOSE OF REVIEW: Developing tailored immunosuppression regimens requires sensitive, non-invasive tools for serial post-transplant surveillance as the current clinical standards with serum creatinine and proteinuria are ineffective at detecting subclinical rejection. The purpose of this review is: (i) to illustrate the rationale for allograft immune monitoring, (ii) to discuss key steps to bring a biomarker from bench-to-bedside, and (iii) to present an overview of promising biomarkers for cellular rejection. SOURCES OF INFORMATION: PubMed. FINDINGS: Recent multicentre prospective observational cohort studies have significantly advanced biomarker development by allowing for the adequately powered evaluation of multiple biomarkers capable of detecting allograft rejection. These studies demonstrate that urinary CXCR3 chemokines (i.e. CXCL9 and CXCL10) are amongst the most promising for detecting subclinical inflammation; increasing up to 30 days prior to biopsy-proven acute rejection; decreasing in response to anti-rejection therapy; and having prognostic significance for the subsequent development of allograft dysfunction. Urinary CXCR3 chemokines are measured by simple and cost-effective ELISA methodology, which can readily be implemented in clinical labs. LIMITATIONS: Many biomarker studies are performed in highly selected patient groups and lack surveillance biopsies to accurately classify healthy transplants. Few validation studies have been done in unselected, consecutive patient populations to characterize population-based diagnostic performance. IMPLICATIONS: Based on these data, prospective interventional trials should be undertaken to determine if chemokine based post-transplant monitoring strategies can improve long-term renal allograft outcomes. This last step will be necessary to move novel biomarkers from the bench-to-bedside. PMID- 26285616 TI - Superstructure of TiO2 Crystalline Nanoparticles Yields Effective Conduction Pathways for Photogenerated Charges. AB - Materials with intricate nanostructures display fascinating properties, which have inspired extensive research on the synthesis of materials with controlled structures. In this study, we investigated the properties of superstructures of TiO2 to understand the inter-relationship between structural ordering and photocatalytic performance. The nanoplate anatase TiO2 mesocrystals were chosen as the typical investigation objects, which were newly synthesized by a topotactic structural transformation. The TiO2 mesocrystals displayed the superstructure of crystallographically ordered alignment of anatase TiO2 nanocrystals with high surface area and large high-energy surface {001} planes exposed. The photoconductive atomic force microscopy and time-resolved diffuse reflectance spectroscopy were utilized to determine the charge transport properties of TiO2 mesocrystals, and their features were highlighted by a comparison with reference TiO2 samples, for example, anatase TiO2 nanocrystals with similar surface area and single crystal structure. Consequently, it was found for the first time that such a superstructure of TiO2 could largely enhance charge separation and had remarkably long-lived charges, thereby exhibiting greatly increased photoconductivity and photocatalytic activity. PMID- 26285617 TI - Organic Semiconductors toward Electronic Devices: High Mobility and Easy Processability. AB - Chemists worldwide are making strong efforts toward finding an organic semiconductor with optimum charge-transport stability and processability properties, approaching the problem from several angles. The number and variety of organic semiconductors have expanded exponentially during the past few years, allowing their classification and identification of the advantages and drawbacks of the different candidates, and leading to an increasingly better understanding of factors affecting charge carrier mobility. In this Perspective, we present different types of materials available, classified according to their supramolecular order. As it will be shown, high intermolecular order, although beneficial for charge transport, may compromise processability. The required balance between processing and high mobility can be achieved only through an adequate design at both the molecular and supramolecular levels. PMID- 26285618 TI - Resolution of a Challenge for Solvation Modeling: Calculation of Dicarboxylic Acid Dissociation Constants Using Mixed Discrete-Continuum Solvation Models. AB - First and second dissociation constants (pKa values) of oxalic acid, malonic acid, and adipic acid were computed by using a number of theoretical protocols based on density functional theory and using both continuum solvation models and mixed discrete-continuum solvation models. We show that fully implicit solvation models (in which the entire solvent is represented by a dielectric continuum) fail badly for dicarboxylic acids with mean unsigned errors (averaged over six pKa values) of 2.4-9.0 log units, depending on the particular implicit model used. The use of water-solute clusters and accounting for multiple conformations in solution significantly improve the performance of both generalized Born solvation models and models that solve the nonhomogeneous dielectric Poisson equation for bulk electrostatics. The four most successful models have mean unsigned errors of only 0.6-0.8 log units. PMID- 26285619 TI - Enhancement of a Two-Photon-Induced Reaction in Solution Using Light-Harvesting Gold Nanodimer Structures. AB - We performed a quantitative analysis of plasmon-assisted two-photon photochromic reactions on light-harvesting gold nanodimer structures. Our strategy for the quantitative analysis of two-photon-induced photochemical reactions on gold nanostructures is using not only a confined photochemical reaction chamber but also a solution system. The strong intensification of near-field light at the nanogap positions on gold nanodimer pairs promoted two-photon absorption by a closed-form diarylethene derivative, resulting in highly efficient photochromic conversion to the open-form structure. PMID- 26285620 TI - Ligand Discrimination in Myoglobin from Linear-Scaling DFT+U. AB - Myoglobin modulates the binding of diatomic molecules to its heme group via hydrogen-bonding and steric interactions with neighboring residues, and is an important benchmark for computational studies of biomolecules. We have performed calculations on the heme binding site and a significant proportion of the protein environment (more than 1000 atoms) using linear-scaling density functional theory and the DFT+U method to correct for self-interaction errors associated with localized 3d states. We confirm both the hydrogen-bonding nature of the discrimination effect (3.6 kcal/mol) and assumptions that the relative strain energy stored in the protein is low (less than 1 kcal/mol). Our calculations significantly widen the scope for tackling problems in drug design and enzymology, especially in cases where electron localization, allostery, or long ranged polarization influence ligand binding and reaction. PMID- 26285621 TI - Electron Hopping Through Single-to-Few-Layer Graphene Oxide Films. Side-Selective Photocatalytic Deposition of Metal Nanoparticles. AB - Single- to few-layer graphene oxide (GO) sheets have been successfully anchored onto TiO2 films using electrophoretic deposition. Upon UV illumination of TiO2-GO films, photogenerated electrons from TiO2 are captured by GO. These electrons are initially used in GO's reduction, while additional electron transfer results in storage across its sp(2) network. In the presence of silver ions, deposition of silver nanoparticles (NPs) is accomplished on the GO surface opposite the TiO2, thus confirming the ability of GO to transport electrons through its plane. Illumination-controlled reduction of silver ions allows for simple selection of particle size and loading, making these semiconductor-graphene-metal (SGM) films ideal for custom catalysis and sensor applications. Initial testing of SGM films as surface-enhanced resonance Raman (SERRS) sensors produced significant target molecule signal enhancements, enabling detection of nanomolar concentrations. PMID- 26285622 TI - Ag@SiO2 Core-Shell Nanostructures: Distance-Dependent Plasmon Coupling and SERS Investigation. AB - Enhancement of Raman signals of pyrene due to the enhanced electric fields on the surface of silver nanoparticles has been investigated by controlling the thickness of the silica shell. Dimeric nanostructures having well-defined gaps between two silver nanoparticles were prepared, and the gap size (d) was varied from 1.5 to 40 nm. The molecules trapped at the dimeric junctions showed higher Raman signal enhancements when the gap was less than 15 nm due to the presence of amplified electric field, in agreement with our theoretical studies. The experimental Raman enhancement factors at the hot spots follow a 1/d(n) dependence, with n = 1.5, in agreement with the recent theoretical studies by Schatz and co-workers. Experimental results presented here on the distance dependence of surface enhanced Raman spectroscopy (SERS) enhancement at the hot spots can provide insight on the design of newer plasmonic nanostructures with optimal nanogaps. PMID- 26285623 TI - Insights from Transient Optoelectronic Analyses on the Open-Circuit Voltage of Organic Solar Cells. AB - In this Perspective, we review recent progress on the use of transient optoelectronic techniques to quantify the processes determining the open-circuit voltage (VOC) of organic solar cells. Most theoretical treatments of VOC include the effects of both material energetics and recombination dynamics, yet most experimental approaches are based on materials energetics alone. We show that by direct measurement of charge carrier dynamics and densities, the rate of nongeminate charge recombination may be determined within working cells and its impact on achievable VOC determined. A simple fit-free device model utilizing these measurements is shown to agree (to within +/-5 mV) with experimentally observed open-circuit voltages for devices comprised of a range of different photoactive layer materials and different processing conditions, and utilizing both bulk and bilayer heterojunctions. This agreement is significantly better than that obtainable from analyzing materials energetics alone, even when employing an in situ analysis of effective electronic band gap. We go on to argue that the precision of our VOC calculations derives from implicitly including the impact of film microstructure on open-circuit voltage. We show that this can modulate VOC by up to 200 mV, and thereby account for the limits of energy-based models in accurately predicting achievable performance. PMID- 26285624 TI - Plasmon Length: A Universal Parameter to Describe Size Effects in Gold Nanoparticles. AB - Localized surface plasmon resonances are central to many sensing and signal transmission applications. Tuning of the plasmon energy and line width through particle size and shape is critical to the design of such devices. To gain quantitative information on the size dependence of plasmonic properties, mainly due to retardation effects, we correlated optical spectra and structures for 500 individual gold particles of five different shapes. We show that the effects of size on the dipolar plasmon frequency and line width are shape-independent when size is described by the plasmon length, the length over which the oscillations take place. This result suggests that edge effects are rather unimportant for dipolar modes in a large size range between 50 and 350 nm. Therefore, in describing the size-dependent plasmonic properties of nanoparticles, one should focus on the distance along which the oscillation occurs rather than its intrinsic shape. PMID- 26285625 TI - Centrifugal Shape Sorting of Faceted Gold Nanoparticles Using an Atomic Plane Selective Surfactant. AB - Highly refined shape populations of gold nanoparticles (AuNPs) are important for emerging applications in catalysis, plasmonics, and nanomaterials growth. To date, research efforts have focused on achieving monodisperse shape by synthetic control or postsynthetic processing that relies on centrifugal sedimentation based sorting schemes where differences in the particle mass and aspect ratios (e.g., rods and spheres) provide a driving force for separation. Here, we present a technique to reversibly modify the sedimentation coefficients of AuNPs possessing different shapes that would otherwise be virtually indistinguishable during centrifugal sedimentation due to their similar densities, masses, and aspect ratios by exploiting the preferential affinity of the surfactant cetyltrimethylammonium bromide (CTAB) for the Au(100) facet. The resulting tailored sedimentation coefficients enable AuNP shape sorting via density gradient centrifugation (DGC). DGC-refined populations of faceted AuNPs are shown to significantly enhance the growth rate of InAs nanowires when used as seed particles, emphasizing the importance of shape control for nanomaterials growth applications. PMID- 26285626 TI - CoSn5 Phase: Crystal Structure Resolving and Stable High Capacity as Anodes for Li Ion Batteries. AB - Tin alloys form a class of interesting high-energy-density anode materials for Li ion batteries, but the improvement of their cycling stability is elusive. Here, we provide new insight on this fatal issue by synthesizing novel CoSn5-phase nanospheres via a conversion chemistry route and directly comparing their cell behavior with that of recently found FeSn5-phase nanospheres. The CoSn5 phase is absent in previous Co-Sn phase diagrams. Co0.83Sn5 nanospheres show a much longer cycle life, which partially is related to milder evolution of their cycling profiles over time. PMID- 26285627 TI - Molecular Balances Based on Aliphatic CH-pi and Lone-Pair-pi Interactions. AB - CH...pi and lone-pair...pi interactions are estimated for a series of conformationally dynamic bicyclic N-aryliimides. On the basis of their strengths and mutual synergy/competition, the molecules prefer a folded/unfolded conformation. Calculations suggest strategies to selectively isolate the folded form by increasing the strength of the attractive CH...pi interaction or removing the lone-pair...pi repulsion. While the barrier for the folded ? unfolded transformation is too large to conformationally lock the molecules in either of the conformers, the dynamics for hopping of the alkyl group across rings and tumbling over the rings are found to be facile in the folded conformation. PMID- 26285628 TI - System-Dependent Signatures of Electronic and Vibrational Coherences in Electronic Two-Dimensional Spectra. AB - In this work, we examine vibrational coherence in a molecular monomer, where time evolution of a nuclear wavepacket gives rise to oscillating diagonal- and off diagonal peaks in two-dimensional electronic spectra. We find that the peaks oscillate out-of-phase, resulting in a cancellation in the corresponding pump probe spectra. Our results confirm the unique disposition of two-dimensional electronic spectroscopy (2D-ES) for the study of coherences. The oscillation pattern is in excellent agreement with the diagrammatic analysis of the third order nonlinear response. We show how 2D-ES can be used to distinguish between ground- and excited-state wavepackets. On the basis of our results, we discuss coherences in coupled molecular aggregates involving both electronic and nuclear degrees of freedom. We conclude that a general distinguishing criterion based on the experimental data alone cannot be devised. PMID- 26285629 TI - Solvent Vapor Annealing of Single Conjugated Polymer Chains: Building Organic Optoelectronic Materials from the Bottom Up. AB - Optoelectronic devices based on organic materials show a strong relationship between the morphological structure of the material and the function of the device. One of the grand challenges in improving the efficiencies of these devices is hence achieving morphological control throughout the entire course of processing. One of the most important postprocessing methods is solvent vapor annealing, which has repeatedly demonstrated its utility in improving the efficiency of organic-material-based devices by changing bulk-film morphology. This Perspective discusses the recent impact of single-molecule spectroscopy techniques in unraveling morphological changes and molecular dynamics and presents solvent vapor annealing as a tool to build organic optoelectronic materials from the bottom up. In particular, we discuss examples of how solvent vapor annealing at the single-chain level can be split into two different regimes, (i) the solvation regime, in which intrachain interactions and molecular dynamics during solvent vapor annealing can be probed, and (ii) the aggregation regime, in which the influence of interchain interactions can be probed. Finally, it will be shown that solvent vapor annealing in the aggregation regime can be used to build highly ordered mesoscopic objects with distinct properties such as long-range energy transfer. PMID- 26285630 TI - Effects of Morphology on the Functionality of Organic Electronic Devices. PMID- 26285631 TI - Support Shape Effect in Metal Oxide Catalysis: Ceria-Nanoshape-Supported Vanadia Catalysts for Oxidative Dehydrogenation of Isobutane. AB - The support effect has long been an intriguing topic in catalysis research. With the advancement of nanomaterial synthesis, the availability of faceted oxide nanocrystals provides the opportunity to gain unprecedented insights into the support effect by employing these well-structured nanocrystals. In this Letter, we show by utilizing ceria nanoshapes as supports for vanadium oxide that the shape of the support poses a profound effect on the catalytic performance of metal oxide catalysts. Specifically, the activation energy of VOx/CeO2 catalysts in oxidative dehydrogenation of isobutane was found to be dependent on the shape of ceria support, rods < octahedra, closely related to the surface oxygen vacancy formation energy and the numbe of defects of the two ceria supports with different crystallographic surface planes. PMID- 26285632 TI - Synthesis of Surface-Functionalized WS2 Nanosheets and Performance as Li-Ion Battery Anodes. AB - Separation of bulk tungsten disulfide (or WS2) into few-layer two-dimensional (2 D) crystals is of interest because of their high surface area for certain chemical processes and size-dependent optical and electronic characteristics. Herein, we demonstrate a process that involves the physical separation of weakly bonded WS2 layers by use of a strong acid treatment (chlorosulfonic acid) at 2 mg/mL, followed by quenching in deionized (DI) water. X-ray photoelectron spectroscopy of the superacid-treated WS2 suggests the formation of W-O type bonds, signifying oxidation of tungsten and reduction of the sulfur phase. Thermogravimetric analysis showed a three-phase weight-loss pattern, suggesting acid functionalization of WS2 surfaces. We also studied the electrochemical behavior of an acid-treated WS2 anode in a lithium half-cell configuration that showed a three-step charge-discharge behavior, characteristic of a conversion reaction. The electrochemical capacity was 118 mAh/g after 50 cycles. PMID- 26285633 TI - What Is the Best Anchoring Group for a Dye in a Dye-Sensitized Solar Cell? AB - We developed a computational procedure to screen many different anchoring groups used or usable to connect a dye to the semiconducting surface in a dye-sensitized solar cell. The procedure leads to a clear identification of the anchoring groups that bind strongly to the surface and facilitate the electron injection at the same time, providing clear-cut indications for the design of new dyes. The complicated interplay of factors that determine the final results (preferred adsorption mode, the anchor's effect on the dye's electronic structure, and dye semiconductor coupling) is illustrated through a few examples showing how chemical intuition can often be misleading in this problem. PMID- 26285634 TI - Modeling Charge Transfer in Fullerene Collisions via Real-Time Electron Dynamics. AB - An approach for performing real-time dynamics of electron transfer in a prototype redox reaction that occurs in reactive collisions between neutral and ionic fullerenes is discussed. The quantum dynamical simulations show that the electron transfer occurs within 60 fs directly preceding the collision of the fullerenes, followed by structural changes and relaxation of electron charge. The consequences of real-time electron dynamics are fully elucidated for the far from equilibrium processes of collisions between neutral and multiply charged fullerenes. PMID- 26285635 TI - Sequential Energy and Electron Transfer in Polynuclear Complex Sensitized TiO2 Nanoparticles. AB - Polynuclear-polypyridyl complexes exhibit a directional energy-transfer property that can improve their photosensitization activity. In the present work, the energy-transfer process is explored in a trinuclear Ru2(?)Os1 complex using transient absorption spectroscopy. This study reveals an efficient excitation energy transfer from the terminal (Ru(II) complex) to the core (Os(II) complex) region in the ultrafast time domain (400 fs-40 ps). The excitation energy funnel is useful in improving the functionalized core activity. This is evidenced in an interfacial electron-transfer study of Ru2(?)Os1, Ru2(?)Ru1, and Os1 complex sensitized TiO2 nanoparticle (TiO2 NP) systems. The intramolecular energy transfer causes sequential excitation of the core part of the Ru2(?)Os1 complex, which leads to multiexponential electron injection into TiO2 NP. Besides this, the electronic coupling between the metal ion centers stabilizes the positive charge within the trinuclear complex, which results in a slow charge recombination reaction. This study shows that polynuclear complexes can be very useful for their panchromatic effects, unidirectional energy- and electron transfer properties. PMID- 26285636 TI - Reaction of HO with CO: Tunneling Is Indeed Important. AB - The potential energy surface and chemical kinetics for the reaction of HO with CO, which is an important process in both combustion and atmospheric chemistry, were computed using high-level ab initio quantum chemistry in conjunction with semiclassical transition state theory under the limiting cases of high and zero pressure. The reaction rate constants calculated from first principles agree extremely well with all available experimental data, which range in temperature over a domain that covers both combustion and terrestrial atmospheric chemistry. The role of quantum tunneling is confirmed to be extremely important, which supports recent work by Continetti and collaborators regarding the loss of hydrogen atoms from vibrationally excited states of HOCO. A sensitivity analysis has been carried out and serves as the basis for a plausible estimate of uncertainty in the calculations. PMID- 26285637 TI - Synthetic Strategy and Structural and Optical Characterization of Thin Highly Crystalline Titanium Disulfide Nanosheets. AB - Two-dimensional (2D) nanomaterials have recently received significant attention because of their attractiveness for use in many nanostructured devices. Layered transition-metal dichalcogenides are of particular interest because reducing their dimensionality causes changes in their already anisotropic physical and chemical properties. The present study describes the first bottom-up solution phase synthesis of thin highly crystalline titanium disulfide (TiS2) nanosheets (NSs) using abundant low-cost molecular precursors. The obtained TiS2 NSs have average dimensions of ~500 nm * 500 nm in the basal plane and have thicknesses of ~5 nm. They exhibit broad absorption in the visible that tails out into the near infrared. The obtained results demonstrate new opportunities in synthesizing low dimensional 2D nanomaterials with potential use in various photochemical energy applications. PMID- 26285638 TI - Chiral Conformation at a Molecular Level of a Propeller-Like Open-Shell Molecule on Au(111). AB - A key stage in engineering molecular functional organizations is represented by controlling the supramolecular assembly of single molecular building blocks, tectons, into ordered networks. Here, we show how an open-shell, propeller-like molecule has been deposited under UHV conditions on Au(111) and its supramolecular organization characterized by scanning tunneling microscopy (STM). Racemic islands were observed at room temperature, and their chirality was imaged at the molecular level at low temperature. Modeling further suggests that the observed chirally alternating ordering dominated by intermolecular interactions is energetically favored. Electron paramagnetic resonance and ultraviolet photoemission spectroscopy evidences suggest that the supramolecular networks may preserve the open-shell character of the tecton. These results represent a fundamental step forward toward the engineering of purely organic spintronic devices. PMID- 26285639 TI - Electrochemical Surface Potential Due to Classical Point Charge Models Drives Anion Adsorption to the Air-Water Interface. AB - We demonstrate that the driving forces for ion adsorption to the air-water interface for point charge models result from both cavitation and a term that is of the form of a negative electrochemical surface potential. We carefully characterize the role of the free energy due to the electrochemical surface potential computed from simple empirical models and its role in ionic adsorption within the context of dielectric continuum theory. Our research suggests that the electrochemical surface potential due to point charge models provides anions with a significant driving force for adsoprtion to the air-water interface. This is contrary to the results of ab initio simulations that indicate that the average electrostatic surface potential should favor the desorption of anions at the air water interface. The results have profound implications for the studies of ionic distributions in the vicinity of hydrophobic surfaces and proteins. PMID- 26285640 TI - BiSI Micro-Rod Thin Films: Efficient Solar Absorber Electrodes? AB - The development of improved solar energy conversion materials is critical to the growth of a sustainable energy infrastructure in the coming years. We report the deposition of polycrystalline BiSI thin films exhibiting promising photoelectrochemical properties on both metal foils and fluorine-doped tin-oxide coated glass slides using a single-source chemical spray pyrolysis technique. Their strong light absorption in the visible range and well-crystallized layered structure give rise to their excellent photoelectrochemical performance through improved electron-hole generation and separation. The structure and surface composition of the films are dependent on deposition temperature, resulting in dramatic differences in performance over the temperature range studied. These results reveal the potential of n-BiSI as an alternative thin film solar energy conversion material and may stimulate further investigation into V-VI-VII compounds for these applications. PMID- 26285641 TI - CuNb3O8: A p-Type Semiconducting Metal Oxide Photoelectrode. AB - A new p-type CuNb3O8 polycrystalline photoelectrode was investigated and was determined to have indirect and direct bandgap sizes of 1.26 and 1.47 eV, respectively. The p-type polycrystalline film could be prepared on fluorine-doped tin oxide glass and yielded a cathodic photocurrent under visible-light irradiation (lambda > 420 nm) with incident photon-to-current efficiencies of up to ~6-7% and concomitant hydrogen evolution. A Mott-Schottky analysis yielded a flat band potential of +0.35 V versus RHE (pH = 6.3) and a calculated p-type dopant concentration of ~7.2 * 10(15) cm(-3). The conduction band energies are found to be negative enough for the reduction of water under visible light irradiation. A hole mobility of ~145 cm(2)/V.s was obtained from J(I)-V(2) measurements using the Mott-Gurney relation, which is ~50% higher than that typically found for p-type Cu2O. DFT-based electronic structure calculations were used to probe the atomic and structural origins of the band gap transitions and carrier mobility. Thus, a new p-type semiconductor is discovered for potential applications in solar energy conversion. PMID- 26285642 TI - B-cell lymphoma-2 localization in the female reproductive tract of the Chinese soft-shelled turtle, Pelodiscus sinensis and its relationship with sperm storage. AB - The aim of the present study was to investigate the expression and localization of B-cell lymphoma-2 (Bcl-2) in the oviduct of the Chinese soft-shelled turtle, Pelodiscus sinensis, during the reproductive cycle to analyze the relationship between Bcl-2 and sperm storage. Bcl-2 expression was confirmed in the P. sinensis oviduct by western blot analysis. Hematoxylin-eosin staining showed that female P. sinensis stored sperm from November to April of the following year. The oviduct showed positive immunostaining for Bcl-2 of epithelial ciliated cells, gland ducts, and gland cells. Bcl-2 expression in the oviduct was associated with sperm storage occurrence. This indicates that the survival factor Bcl-2 may play a role in P. sinensis sperm storage. PMID- 26285643 TI - The effect of immediate breast reconstruction on the timing of adjuvant chemotherapy: a systematic review. AB - Adjuvant chemotherapy is often needed to achieve adequate breast cancer control. The increasing popularity of immediate breast reconstruction (IBR) raises concerns that this procedure may delay the time to adjuvant chemotherapy (TTC), which may negatively impact oncological outcome. The current systematic review aims to investigate this effect. During October 2014, a systematic search for clinical studies was performed in six databases with keywords related to breast reconstruction and chemotherapy. Eligible studies met the following inclusion criteria: (1) research population consisted of women receiving therapeutic mastectomy, (2) comparison of IBR with mastectomy only groups, (3) TTC was clearly presented and mentioned as outcome measure, and (4) original studies only (e.g., cohort study, randomized controlled trial, case-control). Fourteen studies were included, representing 5270 patients who had received adjuvant chemotherapy, of whom 1942 had undergone IBR and 3328 mastectomy only. One study found a significantly shorter mean TTC of 12.6 days after IBR, four studies found a significant delay after IBR averaging 6.6-16.8 days, seven studies found no significant difference in TTC between IBR and mastectomy only, and two studies did not perform statistical analyses for comparison. In studies that measured TTC from surgery, mean TTC varied from 29 to 61 days for IBR and from 21 to 60 days for mastectomy only. This systematic review of the current literature showed that IBR does not necessarily delay the start of adjuvant chemotherapy to a clinically relevant extent, suggesting that in general IBR is a valid option for non metastatic breast cancer patients. PMID- 26285644 TI - Adipocytes can induce epithelial-mesenchymal transition in breast cancer cells. AB - Adipocytes are known to be involved in epithelial-mesenchymal transition (EMT) in several cancers. However, the role of adipocytes in the EMT of breast cancer cells is poorly understood. The purpose of this study was to investigate the involvement of adipocytes in the EMT in breast cancer. Breast cancer cell lines MCF-7, MDA-MB-453, MDA-MB-435S, MDA-MB-231, and MDA-MB-468 were co-cultured with adipocytes and analyzed for morphological changes, proliferation activity, EMT markers, migration, and invasion. In addition, 296 human breast cancer specimens were classified according to the presence of the fibrous or adipose stroma and analyzed by immunohistochemistry for the expression of estrogen and progesterone receptors, human epidermal growth factor receptor 2, antigen Ki-67, N-cadherin, Twist-related protein 1 (TWIST1), high-mobility group AT-hook 2, TGFbeta, and S100 calcium-binding protein A4 using tissue microarray. After co-culture with adipocytes, MCF-7, MDA-MB-435S, and MDA-MB-231 cells exhibited elongated spindle like morphology and increased proliferation; MDA-MB-435S and MDA-MB-231 cells also showed increased dispersion. In all tested breast cancer cells, adipocytes induced migration and invasion. The EMT-like phenotypic changes and increased cell migration and invasion were accompanied by the upregulation of matrix metallopeptidase 9 and TWIST1. Consistently, breast cancer tumors with the adipose stroma showed higher TWIST1 expression than those with the adipose stroma; however, no difference was observed in the levels of other EMT-related proteins. Adipocytes stimulate breast cancer cells to acquire aggressive tumor phenotype by inducing EMT-associated traits, and breast cancer with the adipose stroma expresses EMT markers as breast cancer with the fibrous stroma. PMID- 26285645 TI - Concomitant neoplasms in the skin and stomach unveil the role of type IV collagen and E-cadherin in mucin core protein 5AC expression in vivo. AB - Mucin core protein (MUC) 5AC is a gel-forming glycoprotein that is expressed in different types of tumour cells. MUC5AC expression in cultured cells is regulated through the extracellular matrix and through remodelling by other membranous proteins such as type IV collagen (COL4) and E-cadherin. However, it has not been elucidated whether COL4 and E-cadherin affect MUC5AC expression in tumours in vivo. Here, by analysing a single individual with concomitant neoplasms in the skin [extramammary Paget disease (EMPD)] and the stomach (gastric cancer), we show that MUC5AC expression is reduced in COL4 and membranous E-cadherin expressing EMPD specimens whereas MUC5AC is not abolished in gastric cancer with COL4 negativity and E-cadherin cytoplasmic localization. As the EMPD and gastric cancer specimens were derived from a single patient, each specimen had the same genetic background. These in vivo results support previous in vitro studies which showed that COL4 and E-cadherin downregulated MUC5AC expression. Our study suggests that concomitant neoplasms in different organs of the same individual can serve as a strong tool for uncovering functional diversity in tumour markers in distinct cancer cells. PMID- 26285646 TI - Role of host beta1- and beta2-adrenergic receptors in a murine model of B16 melanoma: functional involvement of beta3-adrenergic receptors. AB - Complex interactions between tumor cells and their surrounding compartment are strongly influenced by the host in which the tumor grows. In melanoma, for instance, stress-associated norephinephrine (NE), acting at beta-adrenergic receptors (beta-ARs), stimulates melanoma cell proliferation and tumor angiogenesis. Among beta-ARs, beta3-ARs play a role acting not only at tumor cells but also at non-neoplastic stromal cells within the melanoma. In the present study, we used a murine model of B16 melanoma to evaluate the role of the host beta1- and beta2-ARs in melanoma growth and we determined whether the role of beta3-ARs can be influenced by the absence of stromal beta1- and beta2-ARs. As compared to wild-type mice, beta1/2-AR knockout mice displayed (i) increased intratumoral levels of both NE and beta3-ARs, as evidentiated at both messenger and protein levels; (ii) increased tumor vascularization; (iii) decreased tumor cell proliferation but increased tumor cell apoptosis; and (iv) increased responsiveness to intratumoral injection of the beta3-AR blocker L-748,337 in terms of decrease in tumor growth, tumor vascular response, tumor cell proliferation, and increase in tumor cell death. These findings together validate the role of beta-AR signaling in melanoma microenvironment suggesting that non neoplastic stromal cells may be targeted by beta-AR-related drugs. The additional fact that beta3-ARs play an important role in melanoma growth suggests selective beta3-AR antagonists as important proapoptotic agents. PMID- 26285648 TI - [Health literacy among less well-educated young people: Influencing factors and consequences]. AB - OBJECTIVES: Health literacy is known to influence health. Findings on the unequal distribution of health literacy among less well-educated young people are presented. The influence of socio-demographic factors and the consequences of a low level of health literacy with regard to health-related behaviour are discussed. MATERIALS AND METHODS: Data from a survey on the health literacy of young people with a lower level of education, older people and migrants (n = 1,000) were used. Health literacy was measured using the instruments of the European Health Literacy Survey (HLS-EU-Q47). RESULTS: The results demonstrate a lower level of health literacy among young people with less education and especially among young migrants. Explanations for a lower level of health literacy among young people with less well-educated young people were parents' educational background and parents' wealth. Migration-related factors had no influence on young people. Further correlations between health literacy and health behaviour were explored. CONCLUSION: It is concluded that health literacy is linked to health behaviour and that unequal distributions of health literacy among young people may increase health inequalities. PMID- 26285647 TI - 4-protein signature predicting tamoxifen treatment outcome in recurrent breast cancer. AB - Estrogen receptor (ER) positive tumors represent the majority of breast malignancies, and are effectively treated with hormonal therapies, such as tamoxifen. However, in the recurrent disease resistance to tamoxifen therapy is common and a major cause of death. In recent years, in-depth proteome analyses have enabled identification of clinically useful biomarkers, particularly, when heterogeneity in complex tumor tissue was reduced using laser capture microdissection (LCM). In the current study, we performed high resolution proteomic analysis on two cohorts of ER positive breast tumors derived from patients who either manifested good or poor outcome to tamoxifen treatment upon recurrence. A total of 112 fresh frozen tumors were collected from multiple medical centers and divided into two sets: an in-house training and a multi center test set. Epithelial tumor cells were enriched with LCM and analyzed by nano-LC Orbitrap mass spectrometry (MS), which yielded >3000 and >4000 quantified proteins in the training and test sets, respectively. Raw data are available via ProteomeXchange with identifiers PXD000484 and PXD000485. Statistical analysis showed differential abundance of 99 proteins, of which a subset of 4 proteins was selected through a multivariate step-down to develop a predictor for tamoxifen treatment outcome. The 4-protein signature significantly predicted poor outcome patients in the test set, independent of predictive histopathological characteristics (hazard ratio [HR] = 2.17; 95% confidence interval [CI] = 1.15 to 4.17; multivariate Cox regression p value = 0.017). Immunohistochemical (IHC) staining of PDCD4, one of the signature proteins, on an independent set of formalin-fixed paraffin-embedded tumor tissues provided and independent technical validation (HR = 0.72; 95% CI = 0.57 to 0.92; multivariate Cox regression p value = 0.009). We hereby report the first validated protein predictor for tamoxifen treatment outcome in recurrent ER-positive breast cancer. IHC further showed that PDCD4 is an independent marker. PMID- 26285649 TI - [Overweight in primary school-age children. Prevalence and risk factors]. AB - BACKGROUND: Various studies show that pre-school age is a sensitive period for the development of overweight and obesity. During a longitudinal study between 2010 and 2013, the municipal health authority (city of Frankfurt) in cooperation with the university children's hospital investigated the development of weight in children aged 5 to 8. MATERIALS AND METHODS: The weight and height of a collective of 5720 children were measured (2010/11). In addition, nutritional and exercise habits, as well as media consumption was documented for 4758 children through a questionnaire during the school enrolment procedure. The weight and height of 3481 children were measured again in the second grade (2012/13). RESULTS: Over a period of 24 months, the percentage of overweight (not obese) children increased from 7.5 to 9.4 % and that of obese children from 4.5 to 5.0 %. 164 of 2818 children with a normal initial weight (5.8 %) changed to percentile class overweight or obese. 79 of 260 children who were initially overweight, not obese (30 %), changed to the group of normal weight, but only 4 out of 156 obese children (3 %). Increased TV consumption (> 1 h per day), availability of their own television, lack of physical activity, and consumption of high-calorie drinks were risk factors for the development of overweight during the primary school age. 72 % of parents of overweight children and 22 % of obese children falsely classified their children as normal weight. CONCLUSIONS: Targeted education about the risk of obesity in the primary school age and offers for early intervention should be established in the healthcare services concerned. PMID- 26285650 TI - [Telematics in the public health sector. Where is the protection of health data?]. AB - There is a long history of telematics in the German health system. Apart from the growing technical possibilities in the field, it is important to concentrate on the protection of health data in telematics applications. Health data in the hands of service providers or other third parties entails certain risks for the patient's personality rights, because these institutions may not be bound by the practice of medical confidentiality. In addition, big data processing risks make the individual lives of patients and insured persons totally transparent. Measures to reduce these risks have to be taken by the providers as well as by the users of telematics infrastructure; they are the ones who should explicitly address the relevant risks and dangers in a data protection and IT-security concept and develop adequate strategies to cope with these dangers. Additionally, the German legislator remains obliged to create a regulatory framework for the protection of patients' rights. PMID- 26285651 TI - Reporting rates for severe hypersensitivity reactions associated with prescription-only drugs in outpatient treatment in Germany. AB - PURPOSE: To determine which 10 prescription-only drugs used in outpatient treatment in Germany are most frequently reported to induce severe drug hypersensitivity reactions taking into account their prescription numbers. In addition, the reader should be made aware of respective databases available to the public and their limitations. METHODS: Reports of anaphylactic and severe cutaneous adverse reactions were identified in the adverse drug reaction database of the German competent authority for the time period January 1998 to December 2012. For frequently reported drugs, the total number of reports was matched with their total number of prescriptions resulting in the reporting rate. RESULTS: Among the 10 drugs with the highest reporting rate for anaphylactic reactions, there were six antibiotics (moxifloxacin, levofloxacin, clindamycin, ciprofloxacin, cefuroxime and amoxicillin), three of which were fluoroquinolones. The other four drugs were glatiramer, metamizole and two angiotensin-converting enzyme inhibitors. Concerning severe cutaneous adverse reactions, four out of ten drugs were antibiotics (clindamycin, sulfamethoxazol + trimethoprim, ciprofloxacin and amoxicillin), and three were anticonvulsives. Because dental prescription numbers were not available to the public, the real reporting rates for clindamycin and to a lesser extent for amoxicillin are presumably lower. CONCLUSIONS: The predominance of antibiotics among the reports of severe immediate and delayed-type drug hypersensitivity reactions is largely in accordance with literature although fluoroquinolones seem to be slightly overrepresented concerning anaphylactic reactions. The reader should be aware of the limitations of adverse drug reaction and prescription databases available to the public, and that over-the-counter drugs, such as non-steroidal anti inflammatory drugs, and drugs typically administered in hospitals could not be considered. PMID- 26285652 TI - Mitochondrial Haplotypes Influence Metabolic Traits in Porcine Transmitochondrial Cybrids. AB - In farm animals, mitochondrial DNA mutations exist widely across breeds and individuals. In order to identify differences among mtDNA haplotypes, two porcine transmitochondrial cybrids were generated by fusion of a Lantang pig cell line devoid of mitochondrial DNA with enucleated cytoplasm from either a Large White pig or a Xiang pig harboring potentially divergent mitochondrial haplotypes. These cybrid cells were subjected to mitochondrial genome sequencing, copy number detecting and analysis of biochemical traits including succinate dehydrogenase (SDH) activity, ATP content and susceptibility to reactive oxygen species (ROS). The Lantang and Xiang mitochondrial genomes were highly homologous with only 18 polymorphic sites, and differed radically from the Large White with 201 and 198 mutations respectively. The Large White and Xiang cybrids exhibited similar mtDNA copy numbers and different values among biochemical traits, generated greater ROS production (P < 0.05) and less SDH activity (P < 0.05) and a lesser ATP content (P < 0.05). The results show that functional differences exist between cybrid cells which differ in mitochondrial genomic background. In conclusion, transmitochondrial cybrids provide the first direct evidence on pig biochemical traits linking different mitochondrial genome haplotypes. PMID- 26285653 TI - Folding propensity of anoplin: A molecular dynamics study of the native peptide and four mutated isoforms. AB - Anoplin, a cationic decapeptide amide GLLKRIKTLL-NH2 derived from venom sac of the solitary wasp Anoplius samariensis has been investigated through Molecular Dynamics. The wild-type (WT) and four isoforms were simulated both in water and in the membrane-mimicking solvent trifluoroethanol (TFE). In water all the investigated species, found to be in rapid equilibrium between different conformational states, can be considered as unfolded. On the other hand, in TFE all the systems enhance their rigidity and, in general, show alpha-helix as the main folded conformation. Interestingly, a semi-quantitative thermodynamic analysis has suggested that the folding driving force is not always the same being in some cases (e.g., the WT Anoplin) of entropic nature and in other cases of energetic nature. PMID- 26285654 TI - Birds of a Feather: Pigeon Head Crest Findings Extend to Domesticated Doves. PMID- 26285655 TI - Peroxiredoxin 6 triggers melanoma cell growth by increasing arachidonic acid dependent lipid signalling. AB - Tumour cells are reported to display an imbalance in the levels of ROS (reactive oxygen species). Frequently, elevated ROS production goes along with compensatory up-regulation of antioxidant enzymes. Accordingly, we found in a previous study that protein levels of several peroxiredoxins, including PRDX6 (peroxiredoxin 6), are highly elevated in experimentally induced melanomas. In the present study, we investigated the functional role of PRDX6 in human melanoma cells. PRDX6 is a bifunctional enzyme, which harbours iPLA2 (Ca(2+)-independent phospholipase A2) activity in addition to its peroxidase function. Our results show that PRDX6 is strongly expressed in most melanoma cells and its expression levels are maintained in a post-transcriptional manner, particularly by EGFR (epidermal growth factor receptor)-dependent signalling. PRDX6 enhances cell viability mainly by enhancing proliferation, which goes along with activation of Src family kinases. Interestingly, we were able to show that the phospholipase activity of the enzyme mediates the pro-proliferative effect of PRDX6. We identified AA (arachidonic acid) as a crucial effector of PRDX6-dependent proliferation and inducer of Src family kinase activation. These results support further the biological importance of the emerging field of lipid signalling in melanoma and highlight the particular functional relevance of PRDX6-dependent phospholipase activity. PMID- 26285656 TI - Doxorubicin inhibits E. coli division by interacting at a novel site in FtsZ. AB - The increase in antibiotic resistance has become a major health concern in recent times. It is therefore essential to identify novel antibacterial targets as well as discover and develop new antibacterial agents. FtsZ, a highly conserved bacterial protein, is responsible for the initiation of cell division in bacteria. The functions of FtsZ inside cells are tightly regulated and any perturbation in its functions leads to inhibition of bacterial division. Recent reports indicate that small molecules targeting the functions of FtsZ may be used as leads to develop new antibacterial agents. To identify small molecules targeting FtsZ and inhibiting bacterial division, we screened a U.S. FDA (Food and Drug Administration)-approved drug library of 800 molecules using an independent computational, biochemical and microbial approach. From this screen, we identified doxorubicin, an anthracycline molecule that inhibits Escherichia coli division and forms filamentous cells. A fluorescence-binding assay shows that doxorubicin interacts strongly with FtsZ. A detailed biochemical analysis demonstrated that doxorubicin inhibits FtsZ assembly and its GTPase activity through binding to a site other than the GTP-binding site. Furthermore, using molecular docking, we identified a probable doxorubicin-binding site in FtsZ. A number of single amino acid mutations at the identified binding site in FtsZ resulted in a severalfold decrease in the affinity of FtsZ for doxorubicin, indicating the importance of this site for doxorubicin interaction. The present study suggests the presence of a novel binding site in FtsZ that interacts with the small molecules and can be targeted for the screening and development of new antibacterial agents. PMID- 26285657 TI - Targeted Disruption of the beta2-Microglobulin Gene Minimizes the Immunogenicity of Human Embryonic Stem Cells. AB - Human embryonic stem cells (hESCs) are a promising source of cells for tissue regeneration, yet histoincompatibility remains a major challenge to their clinical application. Because the human leukocyte antigen class I (HLA-I) molecules are the primary mediators of immune rejection, we hypothesized that cells derived from a hESC line lacking HLA-I expression could be transplanted without evoking a robust immune response from allogeneic recipients. In the present study, we used the replacement targeting strategy to delete exons 2 and 3 of beta2-microglobulin on both gene alleles in hESCs. Because beta2-microglobulin serves as the HLA-I light chain, disruption of the beta2-microglobulin gene led to complete HLA-I deficiency on the cell surface of hESCs and their derivatives. Therefore, these cells were resistant to CD8+ T-cell-mediated destruction. Although interferon-gamma (IFN-gamma) treatment significantly induced beta2 microglobulin expression, promoting CD8+ T cell-mediated killing of control hESCs and their derivatives, CD8+ T-cell-mediated cytotoxicity was barely observed with beta2-microglobulin-null hESCs and their derivatives treated with IFN-gamma. This genetic manipulation to disrupt HLA-I expression did not affect the self-renewal capacity, genomic stability, or pluripotency of hESCs. Despite being relatively sensitive to natural killer (NK) cell-mediated killing due to the lack of HLA-I expression, when transplanted into NK cell-depleted immunocompetent mice, beta2 microglobulin-null hESCs developed into tumors resembling those derived from control hESCs in severe combined immunodeficiency mice. These results demonstrate that beta2-microglobulin-null hESCs significantly reduce immunogenicity to CD8+ T cells and might provide a renewable source of cells for tissue regeneration without the need for HLA matching in the future. SIGNIFICANCE: This study reports the generation of a novel beta2-microglobulin (B2M)-/- human embryonic stem cell (hESC) line. Differentiated mature cells from this line do not express cell surface human leukocyte antigen molecules even after interferon-gamma stimulation and are resistant to alloreactive CD8+ T cells. Moreover, this B2M-/- hESC line contains no off-target integration or cleavage events, is devoid of stable B2M mRNA, exhibits a normal karyotype, and retains its self-renewal capacity, genomic stability, and pluripotency. Although B2M-/- hESC-derived cells are more susceptible to natural killer (NK) cells, murine transplantation studies have indicated that they are, overall, much less immunogenic than normal hESCs. Thus, these data show for the first time that, in vivo, the advantages provided by B2M /- hESC-derived cells in avoiding CD8+ T-cell killing appear significantly greater than any disadvantage caused by increased susceptibility to NK cells. PMID- 26285658 TI - 2005 Donor Eligibility Requirements: Unintended Consequences for Stem Cell Development. AB - Several human embryonic stem cell (hESC)-derived cell therapeutics have entered clinical testing and more are in various stages of preclinical development. The U.S. Food and Drug Administration (FDA) regulates these products under existing regulations and has stated that these products do not constitute a new class of biologic. However, as human tissue, hESCs are subject to regulations that were developed before hESCs were first described. The regulations have not been revised since 2005, well before the first hESC-derived product entered clinical studies. The current regulations require donors of hESCs to be tested in the same manner as donors of tissues intended for transplantation. However, because hESC derived cell products are more than minimally manipulated, they are also subject to the same end-of-production release testing as most other biologic agents. In effect, this makes hESC products subject to redundant testing. No other biologic is subject to a similar testing requirement. Furthermore, the regulations that require donor testing are specifically applicable to hESC cells harvested from donors after a date in 2005. It is unclear which regulations cover hESCs harvested before 2005. Ambiguity in the guidelines and redundant testing requirements have unintentionally created a burdensome regulatory paradigm for these products and reluctance on the part of developers to invest in these promising therapeutics. We propose a simple solution that would address FDA safety concerns, eliminate regulatory uncertainty and risk, and provide flexibility for the FDA in the regulation of hESC-derived cell therapies. SIGNIFICANCE: Regulatory ambiguity concerning donor eligibility screening and testing requirements for human embryonic stem cell lines, in particular those lines created before 2005, are causing significant concern for drug developers. Technically, most of these lines fail to meet eligibility under U.S. Food and Drug Administration (FDA) rules for product licensure, and many developers are unaware that FDA approval to begin trials under an exemption is not an assurance that the FDA will grant licensure of the product. This Perspective outlines the ambiguity and the problem it has caused and proposes a workable solution. The intent is to generate stakeholder and FDA discussion on this issue. PMID- 26285660 TI - Erratum to: Invasive urothelial carcinoma with chordoid features may be an ominous sign predicting sarcomatoid change: a case report of a bladder carcinoma. PMID- 26285661 TI - Erratum to: Pleomorphic leiomyosarcoma with a dedifferentiation-like appearance in the kidney: case report and literature review. PMID- 26285659 TI - In Vivo Effects of Mesenchymal Stromal Cells in Two Patients With Severe Acute Respiratory Distress Syndrome. AB - Mesenchymal stromal cells (MSCs) have been investigated as a treatment for various inflammatory diseases because of their immunomodulatory and reparative properties. However, many basic questions concerning their mechanisms of action after systemic infusion remain unanswered. We performed a detailed analysis of the immunomodulatory properties and proteomic profile of MSCs systemically administered to two patients with severe refractory acute respiratory distress syndrome (ARDS) on a compassionate use basis and attempted to correlate these with in vivo anti-inflammatory actions. Both patients received 2*10(6) cells per kilogram, and each subsequently improved with resolution of respiratory, hemodynamic, and multiorgan failure. In parallel, a decrease was seen in multiple pulmonary and systemic markers of inflammation, including epithelial apoptosis, alveolar-capillary fluid leakage, and proinflammatory cytokines, microRNAs, and chemokines. In vitro studies of the MSCs demonstrated a broad anti-inflammatory capacity, including suppression of T-cell responses and induction of regulatory phenotypes in T cells, monocytes, and neutrophils. Some of these in vitro potency assessments correlated with, and were relevant to, the observed in vivo actions. These experiences highlight both the mechanistic information that can be gained from clinical experience and the value of correlating in vitro potency assessments with clinical effects. The findings also suggest, but do not prove, a beneficial effect of lung protective strategies using adoptively transferred MSCs in ARDS. Appropriate randomized clinical trials are required to further assess any potential clinical efficacy and investigate the effects on in vivo inflammation. SIGNIFICANCE: This article describes the cases of two patients with severe refractory adult respiratory syndrome (ARDS) who failed to improve after both standard life support measures, including mechanical ventilation, and additional measures, including extracorporeal ventilation (i.e., in a heart-lung machine). Unlike acute forms of ARDS (such in the current NIH-sponsored study of mesenchymal stromal cells in ARDS), recovery does not generally occur in such patients. PMID- 26285662 TI - Cognitive outcome in acute simvastatin treatment for aneurysmal subarachnoid hemorrhage: A propensity matched analysis. AB - OBJECTIVES: Experimental evidence has indicated the benefit of simvastatin in the treatment of subarachnoid hemorrhage (SAH). Recently, acute simvastatin treatment was not shown to be beneficial in neurological outcome using modified Rankin Scale. Cognitive function is another important dimension of outcome assessment and yet had not been investigated in statin studies for aneurysmal subarachnoid hemorrhage. We therefore explored whether acute simvastatin treatment would improve cognitive outcomes. METHODS: The study recruited SAH patients with acute simvastatin treatment enrolled in a randomized controlled double-blinded clinical trial (ClinicalTrials.gov Identifier: NCT01038193). A control cohort of SAH patients without simvastatin treatment was identified with propensity score matching of age and admission grade. Primary outcome measure was Montreal Cognitive Assessment (MoCA). Secondary outcome measures were delayed ischaemic deficit (DID), delayed cerebral infarction, modified Rankin Scale (mRS), and Mini Mental State Examination (MMSE). RESULTS: Fifty-one SAH patients with acute simvastatin treatment and 51 SAH patients without simvastatin treatment were recruited for analysis. At 3 months, there were no differences in MoCA scores (MoCA: 21+/-6 vs. 21+/-5, p=0.772). MoCA-assessed cognitive impairment (MoCA<26) was not different (75% vs. 80%, OR 0.7, 95%CI 0.3 to 1.8, p=0.477). There were also no differences in DID, delayed cerebral infarction, favorable mRS outcome, and MMSE scores, and MMSE-assessed cognitive impairment between both groups. CONCLUSIONS: The current study does not support that acute simvastatin treatment improves cognitive outcome after aneurysmal subarachnoid hemorrhage. PMID- 26285663 TI - No relation between sympathetic outflow to muscles and respiratory function in amyotrophic lateral sclerosis. AB - OBJECTIVE: In amyotrophic lateral sclerosis (ALS), not only impairment of motor neurons but also impairment of the autonomic nervous system has been demonstrated by previous physiological studies. Several investigators have reported a correlation between autonomic dysfunction and respiratory dysfunction in ALS. This study analyzed the relation between parameters of respiratory function and muscle sympathetic nerve activity (MSNA) in a large number of ALS patients. METHODS: In 50 patients with ALS (mean age (SD): 62.1 (11.7) years), MSNA, heart rate (HR), and blood pressure (BP) were recorded simultaneously. The arterial oxygen content (PaO2), arterial carbon dioxide content (PaCO2), and forced vital capacity expressed as a percentage of the predicted value for healthy controls (%VC) were determined as parameters of respiratory function. RESULTS: There were no significant correlations between MSNA and PaO2, PaCO2, %VC, or the disability score. Analysis of chronological changes in 14 patients examined twice showed that the disability score and PaCO2 were significantly increased, and %VC was significantly more decreased at the second examination compared with the first examination (p<0.01 and p<0.05, respectively). In contrast, HR, BP, burst rate of MSNA, and age-adjusted MSNA exhibited no significant changes between the first and second examinations. CONCLUSIONS: These findings show that gradual deterioration of respiratory function in ALS patients is not associated with changes of quantitative MSNA parameters, which may suggest that abnormality of the autonomic nervous system is a primary feature of ALS. PMID- 26285664 TI - Prominent cognitive decline and behavioural disturbance in late-onset Alexander disease. PMID- 26285665 TI - An interesting case of characteristic methanol toxicity through inhalational exposure. AB - Methanol poisoning is rare but carries high risk of morbidity and mortality. Most of the cases witnessed in emergency are due to consumption of adulterated alcohol. Here we are reporting a very rare case of methanol poisoning through inhalational exposure leading to putamen necrosis and decreased visual acuity. He had dyselectrolytemia and metabolic acidosis which was successfully managed with early intervention. Its importance lies in the fact that inhalational methanol poisoning is an entity which if picked up early can prevent long-term neurological sequelae. PMID- 26285666 TI - Evaluation of interactive teaching for undergraduate medical students using a classroom interactive response system in India. AB - BACKGROUND: The classical didactic lecture has been the cornerstone of the theoretical undergraduate medical education. Their efficacy however reduces due to reduced interaction and short attention span of the students. It is hypothesized that the interactive response pad obviates some of these drawbacks. The aim of this study was to evaluate the effectiveness of an interactive response system by comparing it with conventional classroom teaching. METHODS: A prospective comparative longitudinal study was conducted on 192 students who were exposed to either conventional or interactive teaching over 20 classes. Pre-test, Post-test and retentions test (post 8-12 weeks) scores were collated and statistically analysed. An independent observer measured number of student interactions in each class. RESULTS: Pre-test scores from both groups were similar (p = 0.71). There was significant improvement in both post test scores when compared to pre-test scores in either method (p < 0.001). The interactive post-test score was better than conventional post test score (p < 0.001) by 8-10% (95% CI-difference of means - 8.2%-9.24%-10.3%). The interactive retention test score was better than conventional retention test score (p < 0.001) by 15-18% (95% CI-difference of means - 15.0%-16.64%-18.2%). There were 51 participative events in the interactive group vs 25 in the conventional group. CONCLUSIONS: The Interactive Response Pad method was efficacious in teaching. Students taught with the interactive method were likely to score 8-10% higher (statistically significant) in the immediate post class time and 15-18% higher (statistically significant) after 8-12 weeks. The number of student-teacher interactions increases when using the interactive response pads. PMID- 26285667 TI - Development of a clickable bimodal fluorescent/PET probe for in vivo imaging. AB - BACKGROUND: Fluorescent imaging agents are becoming evermore important in preclinical and clinical research. They do, however, suffer from poor tissue penetration, which makes optical fluorescence imaging incompatible with whole body imaging techniques. The design of novel bimodal PET active and fluorescent tracers could therefore combine the benefits of optical imaging with radioactively labeled imaging probes. Herein, we report the synthesis and evaluation of a clickable (18)F-labeled fluorescent dye. METHODS: An azide modified BODIPY-Fl dye could be successfully radio-labeled with (18)F using an (18)F/(19)F exchange reaction of the boron-fluoride core of the BODIPY dye to yield a clickable bimodal PET/fluorescent imaging tool. In vitro as well as in vivo imaging (PET/fluorescence) using a bombesin analog was conducted to study the applicability of the dual-modality imaging probe. RESULTS: We use the radio labeled small molecule, (18)F-BODIPY-azide to label site-specifically different targeted peptides, based on a standard modular labeling protocol. Following the synthesis of a bimodal bombesin analog, we determine the peptide tracer's performance in vitro and in vivo, exploring both the optical as well as PET imaging capabilities. CONCLUSION: This versatile methodology has the potential to have a transformational impact on (18)F radiotracer synthesis, opening the door for rapid screening of novel-labeled peptide tracers, both on the cellular (optical) as well as whole-body (PET) level. PMID- 26285668 TI - Treatment of periprosthetic femoral fractures with modular stems. AB - PURPOSE: The purpose of this study was to analyse the efficacy of modular femoral stems for the treatment of certain post-operative periprosthetic fractures in patients with hip arthroplasty. METHODS: Of a total series of 61 modular revision stems, 17 were used to address periprosthetic femoral fractures and 12 of these are the object of this study. The average follow-up was 3.7 years (range 1-14 years). The evaluations were performed at three and six months, and then annually using the HHS score and radiographic studies for the assessment of loosening, subsidence and bone integration of the stem. RESULTS: Seven cases had type B2 fractures and five type B3 ones. All patients walked freely, eight of them using canes. HHS improved to a post-operative mean of 78 (range 72-83). Radiographically, fracture healing was observed at three months in nine cases. In six cases stem subsidence of a mean of 3.9 mm (range 2-12 mm) was observed, which stabilized a year following implantation and did not need revision surgery. In two cases a subsequent dislocation (at three and seven months after surgery) occurred, which were treated with constrained acetabular systems. In nine cases hypotrophy of the cortex in the diaphyseal area was noted, which did not alter the patients' clinical course. CONCLUSION: Modular femoral stems are an acceptable treatment in type B2 and B3 periprosthetic fractures. PMID- 26285669 TI - The use of customized cages in revision total hip arthroplasty for Paprosky type III acetabular bone defects. AB - PURPOSE: Revision total hip arthroplasty (THA) is challenging if severe periacetabular bone loss is present. Here we describe a method that uses a customised cage to reconstruct an acetabulum with a massive bone defect. METHODS: Designed with the aid of the rapid prototyping technique, a customised cage with a hook, crest and flange or braids was made, and then utilized to reconstruct severe compromised acetabulum in revision THA since 2001. Twenty-two patients (23 hips) were included in this study. The mean patient age at the time of surgery was 60.9 years (range, 38-80 years). Three hips had massive acetabular bone defects of Paprosky type IIIA and 20 of type IIIB. The Harris hip score was used to evaluate hip function. Radiographs were taken to evaluate loosening of the cage and resorption of allograft bone. RESULTS: The average follow up was 81.6 +/ 24.9 months. The mean Harris hip score improved from 39.6 pre-operatively to 80.9 at the final follow-up. There were no instances of deep infection, severe venous thrombosis, and nerve palsy. One patient who had an intra-operative rupture of the superior acetabular artery was successfully treated using the haemostatic suturing technique. Two patients experienced dislocation at post operative days four and six, respectively, and both were treated with closed reduction and skin traction for three weeks. CONCLUSIONS: The present study demonstrates that a customised cage may be a promising option for THA revision of severely compromised acetabula. Extended follow-up is necessary to evaluate the long-term performance of this approach. PMID- 26285670 TI - Pulse Generator Exchange Does Not Accelerate the Rate of Electrical Failure in a Recalled Small Caliber ICD Lead. AB - BACKGROUND: St. Jude Riata/Riata ST defibrillator leads (St. Jude Medical, Sylmar, CA, USA) were recalled by the Food and Drug Administration in 2011 for an increased rate of failure. More than 227,000 leads were implanted and at least 79,000 patients still have active Riata leads. Studies have examined clinical predictors of lead failure in Riata leads, but none have addressed the effect of implantable cardioverter defibrillator (ICD) generator exchange on lead failure. The purpose of this study is to assess the effect of ICD generator exchange on the rate of electrical failure in the Riata lead at 1 year. METHODS: A retrospective chart review was conducted in patients who underwent implantation of a Riata/Riata ST lead at one center. Patients with a functioning Riata lead (with/without externalized conductor) at the time of ICD exchange were compared to controls with Riata leads implanted for a comparable amount of time who did not undergo generator replacement. RESULTS: Riata leads were implanted in 1,042 patients prior to the recall and 153 of these patients underwent generator exchange without lead replacement. Conductor externalization was noted in 21.5% of Riata leads in the ICD exchange cohort, which was not different from the control group (19.2%; P = 0.32). Two leads failed in the first year after generator replacement (1.5%) which did not significantly differ from the control group (2.0%; P = 0.57). At change-out, 54% received a commanded shock (18.6 +/- 0.9 J) that did not result in any change in the high-voltage lead impedance (46.1 +/- 1.1 ohms). CONCLUSIONS: Conductor externalization was seen frequently in our cohort of patients. ICD generator exchange did not accelerate the rate of Riata lead failure at 1 year. Although both the control and the change-out cohorts failed at a rate much greater than nonrecalled leads, generator exchange did not appear to add to the problem. PMID- 26285671 TI - fMRat: an extension of SPM for a fully automatic analysis of rodent brain functional magnetic resonance series. AB - The purpose of this study was to develop a multi-platform automatic software tool for full processing of fMRI rodent studies. Existing tools require the usage of several different plug-ins, a significant user interaction and/or programming skills. Based on a user-friendly interface, the tool provides statistical parametric brain maps (t and Z) and percentage of signal change for user-provided regions of interest. The tool is coded in MATLAB (MathWorks((r))) and implemented as a plug-in for SPM (Statistical Parametric Mapping, the Wellcome Trust Centre for Neuroimaging). The automatic pipeline loads default parameters that are appropriate for preclinical studies and processes multiple subjects in batch mode (from images in either Nifti or raw Bruker format). In advanced mode, all processing steps can be selected or deselected and executed independently. Processing parameters and workflow were optimized for rat studies and assessed using 460 male-rat fMRI series on which we tested five smoothing kernel sizes and three different hemodynamic models. A smoothing kernel of FWHM = 1.2 mm (four times the voxel size) yielded the highest t values at the somatosensorial primary cortex, and a boxcar response function provided the lowest residual variance after fitting. fMRat offers the features of a thorough SPM-based analysis combined with the functionality of several SPM extensions in a single automatic pipeline with a user-friendly interface. The code and sample images can be downloaded from https://github.com/HGGM-LIM/fmrat . PMID- 26285672 TI - Microemulsion-Based Topical Hydrogels of Tenoxicam for Treatment of Arthritis. AB - Tenoxicam (TNX) is a non-steroidal anti-inflammatory drug (NSAID) used for the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, backache and pain. However, prolonged oral use of this drug is associated with gastrointestinal adverse events like peptic ulceration, thus necessitating its development as topical formulation that could obviate the adverse effects and improve patient compliance. The present study was aimed at development of microemulsion-based formulations of TNX for topical delivery at the affected site. The pseudoternary phase diagrams were developed and microemulsion formulations were prepared using Captex 300/oleic acid as oil, Tween 80 as surfactant and n-butanol/ethanol as co-surfactant. Optimized microemulsions were characterized for drug content, droplet size, viscosity, pH and zeta potential. The ex vivo permeation studies through Laca mice skin were performed using Franz diffusion cell assembly, and the permeation profile of the microemulsion formulation was compared with aqueous suspension of drug and drug incorporated in conventional cream. Microemulsion formulations of TNX showed significantly higher (p < 0.001) mean cumulative percent permeation values in comparison to conventional cream and suspension of drug. In vivo anti-arthritic and anti inflammatory activity of the developed TNX formulations was evaluated using various inflammatory models such as air pouch model, xylene-induced ear edema, cotton pellet granuloma and carrageenan-induced inflammation. Microemulsion formulations were found to be superior in controlling inflammation as compared to conventional topical dosage forms and showed efficacy equivalent to oral formulation. Results suggest that the developed microemulsion formulations may be used for effective topical delivery of TNX to treat various inflammatory conditions. PMID- 26285673 TI - Development and Evaluation of a Novel Delivery System Containing Phytophospholipid Complex for Skin Aging. AB - Citrus auranticum and Glycyrrhiza glabra are rich in anti-oxidant polyphenols helpful in prevention of skin aging. Polyphenols have high polarity and lower skin penetration resulting in lower cutaneous delivery. The present work is attempted to develop a novel polyherbal phospholipid complex cream to improve cutaneous delivery of polyphenols for sustained anti-oxidant action. Phytochemical and in vitro anti-oxidant evaluation was done on methanolic extracts of orange peel and liquorice powder. Total phenolic content, total flavonoid content, and anti-oxidant assays were done on different ratios of orange peel and liquorice extract. Ratio 1:2 gave highest total phenolic content (TPC) (530.00 +/- 1.56 mg gallic acid equivalent (GAE) g(-1) extract), total flavonoid content (TFC) (246.25 +/- 1.03 mg rutin equivalent (RUE) g(-1) extract), 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity (87.99 +/- 0.64%), and H2O2 scavenging activity (72.47 +/- 0.86%) and hence was used for formulation. Solvent evaporation method using methanol with 1:1 extract to phospholipid ratio was found to have entrapment efficiency of 93.22 +/- 0.26%. Evaluation parameters like scanning electron microscopy (SEM), Fourier transform infrared spectrophotometry (FT-IR), and differential scanning calorimetry (DSC) confirmed formation of complex. The complex was formulated as oil-in-water cream and evaluated for various parameters. The optimized cream containing 1% complex was non-irritant and was found to be stable for 3-month period under conditions of stability study. Ex vivo diffusion studies showed that extract phospholipid complex cream had better retention of polyphenols in the skin when compared to conventional extract cream giving prolonged and stronger topical action. The cream had an anti-elastase activity of 28.02 +/- 0.95% at concentration of 3000 MUg ml(-1) (w/v). Thus, the developed safe and stable polyherbal phytophospholipid complex cream exhibited good potential as anti-aging cosmeceutical. PMID- 26285674 TI - Differential Diagnosis of Cystic Pancreatic Lesions Including the Usefulness of Biomarkers. AB - BACKGROUND: Cystic pancreatic lesions are more and more often found. Malignant risk ranges from nil to more than 60%. A precise diagnosis is required to adapt surveillance or therapeutic strategy. METHODS: We tried to identify the most difficult differential diagnoses encountered in a tertiary center of pancreatology and to guide the reader as how to reach the correct strategy and diagnosis in these situations. RESULTS: We identified eight clinically difficult situations: i) chronic pancreatitis versus intraductal papillary mucinous neoplasms, ii) serous versus mucinous cystic neoplasms, iii) serous cystic neoplasms versus branch-duct intraductal papillary mucinous neoplasms, iv) intraductal papillary mucinous neoplasms versus acinar cell cystadenoma, v) (pseudo-) solid serous cystic neoplasm versus neuroendocrine tumor, vi) pancreatic neuroendocrine tumors versus solid pseudopapillary tumors, vii) cystic forms of a solid tumor, and viii) rare pancreatic or peripancreatic cystic lesions. The work-up should rely on computed tomography scan, pancreatic magnetic resonance imaging, and, only if necessary, endoscopic ultrasound with or without fine needle aspiration. CONCLUSION: An expert analysis of imaging data allows a precise diagnosis in most of the cases. Pancreatic resection should no longer be performed in case of diagnostic doubt. PMID- 26285675 TI - A large multiexonic genomic deletion within the ALMS1 gene causes Alstrom syndrome in a consanguineous Pakistani family. PMID- 26285676 TI - Transcriptome-wide dynamics of RNA pseudouridylation. AB - Pseudouridylation is the most abundant internal post-transcriptional modification of stable RNAs, with fundamental roles in the biogenesis and function of spliceosomal small nuclear RNAs (snRNAs) and ribosomal RNAs (rRNAs). Recently, the first transcriptome-wide maps of RNA pseudouridylation were published, greatly expanding the catalogue of known pseudouridylated RNAs. These data have further implicated RNA pseudouridylation in the cellular stress response and, moreover, have established that mRNAs are also targets of pseudouridine synthases, potentially representing a novel mechanism for expanding the complexity of the cellular proteome. PMID- 26285677 TI - Organelle dynamics: regulation of mitochondrial function by diet. PMID- 26285678 TI - The molecular era of the mitochondrial calcium uniporter. AB - The mitochondrial calcium uniporter is an evolutionarily conserved calcium channel, and its biophysical properties and relevance to cell death, bioenergetics and signalling have been investigated for decades. However, the genes encoding this channel have only recently been discovered, opening up a new 'molecular era' in the study of its biology. We now know that the uniporter is not a single protein but rather a macromolecular complex consisting of pore forming and regulatory subunits. We review recent studies that harnessed the power of molecular biology and genetics to characterize the mechanism of action of the uniporter, its evolution and its contribution to physiology and human disease. PMID- 26285683 TI - Bilateral Retinal Detachments Caused by Severe Preeclampsia Diagnosed with Point of-Care Ultrasound. AB - Bilateral retinal detachments are a rare complication of preeclampsia. We present a case report of a patient with an unknown pregnancy who presented with acute bilateral vision loss and elevated blood pressure. Point-of-care ocular ultrasound revealed bilateral retinal detachments. She was diagnosed with severe preeclampsia and taken for an urgent caesarean section with the delivery of a 26 week-old infant. PMID- 26285679 TI - Specificity and nonspecificity in RNA-protein interactions. AB - To fully understand the regulation of gene expression, it is critical to quantitatively define whether and how RNA-binding proteins (RBPs) discriminate between alternative binding sites in RNAs. Here, we describe new methods that measure protein binding to large numbers of RNA variants, and ways to analyse and interpret data obtained by these approaches, including affinity distributions and free energy landscapes. We discuss how the new methodologies and the associated concepts enable the development of inclusive, quantitative models for RNA-protein interactions that transcend the traditional binary classification of RBPs as either specific or nonspecific. PMID- 26285686 TI - Structural and magnetic properties of mixed Co-Ln (Ln = Nd, Sm, Eu, Gd and Ho) diethyleneglycolate complexes. AB - New hybrid compounds LnCoCl(deg)2 (deg = diethyleneglycolate; Ln = Nd, Sm, Eu, Gd and Ho) have been synthesized by mixing cobalt and rare earth cations in a boiling diethyleneglycol (degH2) medium. Their crystallographic structures have been ab initio solved from synchrotron powder diffraction data. They consist of edge sharing tetrameric sub-units [(Ln2Co2)(deg)4(Cl)2] forming 1D infinite chains along the c parameter of a monoclinic unit cell (SG = C2/c). The five- and seven-coordination of Co(2+) and Ln(3+) cations inferred from the crystallographic results is confirmed by UV-visible absorption and Extended X-ray Absorption Fine Structure (EXAFS) spectroscopy. In the LnCoCl(deg)2 (Ln = Nd, Sm, Eu, Gd, Ho) series, weak antiferromagnetic superexchange interactions have been evidenced, between high spin Co(2+) and Ln(3+) orbitally degenerate cations. These materials are considered as potential precursors for the simultaneous reduction of Co-Ln-glycolate species into bimetallic nanoparticles by the polyol process. PMID- 26285684 TI - Membrane microparticles: shedding new light into cancer cell communication. AB - BACKGROUND: Microparticles (MPs) or ectosomes are small enclosed fragments (from 0.2 to 2 MUm in diameter) released from the cellular plasma membrane. Several oncogenic molecules have been identified inside MPs, including soluble proteins XIAP, survivin, metalloproteinases, CX3CL1, PYK2 and other microRNA-related proteins; membrane proteins EGFR, HER-2, integrins and efflux pumps; and messenger RNAs and microRNAs miR-21, miR-27a, let-7, miR-451, among others. Studies have shown that MPs transfer their cargo to neoplastic or non-malignant cells and thus contribute to activation of oncogenic pathways, resulting in cell survival, drug resistance and cancer dissemination. DISCUSSION AND CONCLUSION: This review summarizes recent findings on MP biogenesis and the role of the MPs cargo in cancer and discusses some of the RNAs and proteins involved. In addition, the discussion covers evidence of (1) how and which signaling pathways can be activated by MPs in recipient cells; (2) recipient cell-type selectivity in incorporation of proteins and RNAs transported by MPs; and (3) how upon stimulation, stromal cells release MPs, promoting resistance to chemotherapeutics and invasiveness in cancer cells. PMID- 26285685 TI - Comparison of individual component deletions in a glucose-specific phosphotransferase system revealed their different applications. AB - The phosphoenolpyruvate-dependent glucose-specific phosphotransferase system (PTS(Glc)) is the main glucose uptake pathway in Escherichia coli that affects both substrate assimilation and metabolism leading to the product formation. In this study, the effect of single PTS(Glc) mutation on cell growth and substrate consumption was investigated by knocking out the genes involved in the phosphotransfer cascade of the PTS(Glc). In addition, the distribution of the metabolites of mutants was analyzed. Each mutant was confirmed to have different adaptability in the presence of both glucose and xylose with different ratios, and a substrate mixture with high xylose content can be completely consumed in short time when the ptsI mutant is employed. Finally, ptsH deletion was for the first time applied for succinate production due to its well performance under anaerobic condition. Strain YL104H, in which ptsH was deleted, exhibited considerably increased succinate yield under both aerobic and anaerobic conditions. The succinate titer and overall productivity reached 511.11 mM and 1.01 g/L/h after 60 h during the whole-phase fermentation in a mineral salt medium. The present results demonstrated the glucose and xylose co-utilization efficiency and the product yield and productivity can be significantly improved if a suitable PTS(Glc) deletion mutant was selected. PMID- 26285687 TI - Bioinspired Nano-Prodrug with Enhanced Tumor Targeting and Increased Therapeutic Efficiency. AB - Nanotechnology-based drug delivery has a great potential to revolutionize cancer treatment by enhancing anticancer drug efficacy and reducing drug toxicity. Here, a bioinspired nano-prodrug (BiNp) assembled by an antineoplastic peptidic derivative (FA-KLA-Hy-DOX), a folate acid (FA)-incorporated proapoptotic peptide (KLAKLAK)(2) (KLA) to doxorubicin (DOX) via an acid-labile hydrozone bond (Hy) is constructed. The hydrophobic antineoplastic agent DOX is efficiently shielded in the core of nano-prodrug. With FA targeting moieties on the surface, the obtained BiNp shows significant tumor-targeting ability and enhances the specific uptake of cancer cells. Upon the trigger by the intracellular acidic microenvironment of endosomes, the antineoplastic agent DOX is released on-demand and promotes the apoptosis of cancer cells. Simultaneously, the liberated FA-KLA can induce the dysfunction of mitochondria and evoke mitochondria-dependent apoptosis. In vitro and in vivo results show that the nano-prodrug BiNp with integrated programmed functions exhibits remarkable inhibition of tumor and achieves a maximized therapeutic efficiency with a minimized side effect. PMID- 26285688 TI - Gap junctional protein Cx43 is involved in the communication between extracellular vesicles and mammalian cells. AB - Intercellular communication is vital to ensure tissue and organism homeostasis and can occur directly, between neighbour cells via gap junctions (GJ), or indirectly, at longer distances, through extracellular vesicles, including exosomes. Exosomes, as intercellular carriers of messenger molecules, mediate the transfer of biological information between donor and acceptor cells. Although the biological effects of exosomes in target cells have been intensively studied, the mechanisms that govern exosomal uptake are not fully understood. Here, we show that Connexin 43 (Cx43), the most widely expressed GJ protein, is present in exosomes in the form of hexameric channels and, more importantly, that exosomal Cx43 is able to modulate the interaction and transfer of information between exosomes and acceptor cells. This study envisions a new paradigm where Cx43 containing channels mediate the release of exosomal content into cells, which constitutes a novel and unanticipated mechanism to modulate intercellular communication. PMID- 26285689 TI - Reusable and specific proton transfer signalling by inorganic cyanide in solution and solid phase. AB - A highly specific cyanide mediated proton transfer signalling (PTS) is exhibited by a simple diaminomalenonitrile (DAMN) derivative 1. By virtue of the functional groups on it, the chromophore offered a rigid anchoring on a silica surface via a simple dip method, while retaining the recognition behaviour. The PTS triggered a prompt dual-modal display i.e., chromogenic and fluorogenic. The signal readout can be visualized even in micromolar concentrations. It is noteworthy that PTS can be reversed in both solution and solid phases. The remarkable sensitivity of 1 to detect CN(-) from the solution and solid phase envisages a pivotal step towards field-usable sensing. PMID- 26285690 TI - Neutrophil function in young and old caregivers. AB - OBJECTIVE: The present study examined the effects of caregiving stress and ageing on neutrophil function in young and older individuals. DESIGN: As a model of caregiving, young parents (aged 38.3 +/- 4.78) of children with developmental disabilities were recruited and compared to older caregivers (aged 70 +/- 6.03), full time carers of a spouse with dementia. Age- and gender-matched controls were also assessed. METHODS: Participants completed a questionnaire pack assessing health behaviours, psychosocial status and caregiving characteristics, and provided a blood sample for assay of neutrophil function (phagocytosis of Escherichia coli and generation of reactive oxygen species to E. coli). RESULTS: Despite scoring poorly on the majority of psychological and caregiving variables, neutrophil function in caregivers was comparable to that in controls and was unexpectedly higher in older adults when compared to younger adults overall. However, those caregivers who reported higher psychological morbidity (depression, perceived stress, poor sleep quality), and more burdensome caregiving showed some evidence of poorer neutrophil phagocytic function. CONCLUSION: To our knowledge, this is the first study to examine the effect of caregiving stress on neutrophil function in young and older participants simultaneously. Overall, neutrophil function was preserved in caregivers with neutrophil phagocytosis compromised only in those with the highest levels of distress. This suggests that, in future studies, more attention should be paid to individual differences among caregivers rather than caregiving status per se. STATEMENT OF CONTRIBUTION: What is already known on this subject? Ageing is accompanied by the decrease in innate and adaptive immunity, termed immunosenescence. Caregiving stress has been shown to exert negative effect on immune function in both young and old. What does this study add? The study examined effect of caregiving and ageing simultaneously in four groups of participants. Neutrophil function and stress hormone levels were preserved in the stressed in both age groups. Those with higher psychological morbidity had poorer neutrophil phagocytosis. PMID- 26285691 TI - Nitric Oxide Contributes to Vasomotor Tone in Hypertensive African Americans Treated With Nebivolol and Metoprolol. AB - Endothelial dysfunction is more prevalent in African Americans (AAs) compared with whites. The authors hypothesized that nebivolol, a selective beta1 antagonist that stimulates nitric oxide (NO), will improve endothelial function in AAs with hypertension when compared with metoprolol. In a double-blind, randomized, crossover study, 19 AA hypertensive patients were randomized to a 12 week treatment period with either nebivolol 10 mg or metoprolol succinate 100 mg daily. Forearm blood flow (FBF) was measured using plethysmography at rest and after intra-arterial infusion of acetylcholine and sodium nitroprusside to estimate endothelium-dependent and independent vasodilation, respectively. Physiologic vasodilation was assessed during hand-grip exercise. Measurements were repeated after NO blockade with L-N(G) -monomethylarginine (L-NMMA) and after inhibition of endothelium-derived hyperpolarizing factor (EDHF) with tetraethylammonium chloride (TEA). NO blockade with L-NMMA produced a trend toward greater vasoconstriction during nebivolol compared with metoprolol treatment (21% vs 12% reduction in FBF, P=.06, respectively). This difference was more significant after combined administration of L-NMMA and TEA (P<.001). Similarly, there was a contribution of NO to exercise-induced vasodilation during nebivolol but not during metoprolol treatment. There were significantly greater contributions of NO and EDHF to resting vasodilator tone and of NO to exercise induced vasodilation with nebivolol compared with metoprolol in AAs with hypertension. PMID- 26285692 TI - Variation in hospital caesarean section rates for women with at least one previous caesarean section: a population based cohort study. AB - BACKGROUND: Internationally, repeat caesarean sections make the largest contribution to overall caesarean section rates and inter-hospital variation has been reported. The aim of this study was to determine if casemix and hospital factors explain variation in hospital rates of repeat caesarean sections and whether these rates are associated with maternal and neonatal morbidity. METHODS: This population-based record linkage study utilised data from New South Wales, Australia between 2007 and 2011. The study population included maternities with any previous caesarean section(s) and were singleton, cephalic and >= 37 weeks' gestation (Robson Group 5). Multilevel regression models were used to examine variation in hospital rates of 'planned repeat caesarean section' and, among women who planned a vaginal birth, 'intrapartum caesarean section'. We assessed associations between risk-adjusted hospital rates of planned and intrapartum caesarean sections and rates of casemix adjusted maternal and neonatal morbidity, postpartum haemorrhage and Apgar score <7 at five minutes. RESULTS: Of 61894 maternities with a previous caesarean section in 81 hospitals, 82.1% resulted in a caesarean section (72.7% planned and 9.4% unplanned intrapartum caesareans) and 17.9% in vaginal birth. Observed hospital rates of planned caesarean sections ranged from 50.7% to 98.4%. Overall 49.0% of between-hospital variation in planned repeat caesarean section rates was explained by patient (17.3%) and hospital factors (31.7%). Increased odds of planned caesarean section were associated with private hospital status and lower hospital propensity for vaginal birth after caesarean. There were no associations between hospital rates of planned repeat caesarean section and adjusted morbidity rates. Among women who intended a vaginal birth, the observed rates of intrapartum caesarean section ranged from 12.9% to 71.9%. In total, 27.5% of between-hospital variation in rates of intrapartum caesarean section was explained by patient (19.5%) and hospital factors (8.0%). The adjusted morbidity rates differed among hospital intrapartum caesarean section rates, but were influenced by a few hospitals with outlying morbidity rates. CONCLUSIONS: Among women with at least one previous caesarean section, less than half of the variation in hospital caesarean section rates was explained by differences in hospital's patient characteristics and practices. Strategies aimed at modifying caesarean section rates for these women should not affect morbidity rates. PMID- 26285693 TI - Understanding the information needs of women with rheumatoid arthritis concerning pregnancy, post-natal care and early parenting: A mixed-methods study. AB - BACKGROUND: Although women with rheumatoid arthritis (RA) face a number of challenges in negotiating the journey to parenthood, no studies have explored the information needs of women with RA in relation to their childbearing years. This study aimed to determine the need for (and preferred mode/s of delivery of) information regarding pregnancy, post-natal care and early parenting among women with RA. METHODS: Interviews and focus groups were conducted with 27 women with RA who were pregnant in the last 5 years, currently pregnant or planning pregnancy. Verbatim transcripts were analysed using both inductive and deductive approaches. Two validated instruments were used to quantify information needs and preferences: the Educational Needs Assessment Tool (ENAT, range 0-156, higher scores indicate higher educational needs) and the Autonomy Preference Index (API, range 0-100, higher scores indicate stronger preferences). RESULTS: Lack of information about medication safety, access to physical/emotional support services and practical strategies for coping with daily challenges related to parenting were the most prominent of the six key themes identified. Rheumatologists were the primary source for information regarding treatment decisions while arthritis consumer organisations were perceived as critical 'resource hubs'. There was strong preference for information delivered electronically, especially among rural participants. Quantitative outcomes supported the qualitative findings; on average, participants reported high educational needs (mean ENAT score 97.2, SD 30.8) and API scores indicated that desire for information (mean 89.8, SD 5.6) was greater than the need for involvement in treatment decision-making (mean 68.4, SD 8.2). CONCLUSIONS: Many women with RA struggle to find adequate information on pregnancy planning, pregnancy and early parenting in relation to their chronic condition, and there is a clear need to develop accessible information that is consumer-focused and evidence-based. Although most participants trusted their rheumatologist as their primary information source, there was consistent demand for more information, particularly regarding the safety of RA medications during pregnancy and breastfeeding, and the importance of learning from other women's personal experiences was strongly emphasised. PMID- 26285694 TI - Co-existing of adenoid cystic carcinoma and invasive squamous cell carcinoma of the uterine cervix: a report of 3 cases with immunohistochemical study and evaluation of human papillomavirus status. AB - BACKGROUNDS: The aim of this study was to describe the clinicopathological characteristics and high-risk human papillomavirus (HPV) infection status in patients diagnosed with co-existing of adenoid cystic carcinoma (ACC) and invasive squamous cell carcinoma (SCC) of the uterine cervix. METHODS: Three patients were identified from the pathology databank of Peking Union Medical College Hospital from year 2000 to 2014. Immunohistochemistry and in situ hybridization (ISH) were employed in this study. RESULTS: The patients were aged 64, 77 and 63 years (average, 68 years old). All the patients were postmenopausal women who presented with bloody or watery vaginal discharge. The cervical cytology screening results were all suspicious for high-grade squamous intraepithelial lesion (HSIL). The subsequent cervical colposcopy biopsies all showed cervical intraepithelial neoplasia III (CINIII). One patient received only a cervical conization, whereas the other two patients underwent hysterectomy. The immunohistochemical results showed that the ACC compartments were positive for CK7 and CD117; the cases of SCC were negative for CK7 and CD117. P63 staining was strongly positive and diffuse throughout the SCC compartments, whereas only patchy positive areas were observed in the ACC. MYB exhibited strong nuclear staining in the ACC and SCC compartments but negative staining in the endocervical gland. In situ hybridization (ISH) signals for high-risk HPV DNA and mRNA were present in the two compartments of all three patients. The patients had no evidence of disease at an average follow-up time of 21.6 months. CONCLUSION: High-risk HPV was present in both the ACC and SCC compartments in all three patients. PMID- 26285695 TI - Long-term safety and efficacy of antithymocyte globulin induction: use of integrated national registry data to achieve ten-year follow-up of 10-10 Study participants. AB - BACKGROUND: Rabbit antithymocyte globulin (rATG, Thymoglobulin(r)) is the most common induction immunosuppression therapy in kidney transplantation. We applied a database integration strategy to capture and compare long-term (10-year) outcome data for US participants in a clinical trial of rATG versus FDA-approved basiliximab. METHODS: Records for US participants in an international, 1-year, randomized clinical trial comparing rATG and basiliximab induction in deceased donor kidney transplantation were integrated with records from the US national Organ Procurement and Transplantation (OPTN) registry using center, transplant dates, recipient sex, and birthdates. The OPTN captures center-reported acute rejection, graft failure, death, and cancer events, and incorporates comprehensive death records from the Social Security Death Master File. Ten-year outcomes according to randomized induction regimen were compared by Kaplan-Meier analysis (two-sided P). Non-inferiority of rATG was assessed using a one-tailed equivalence test (a-priori equivalence margins of 0-10 %). RESULTS: Of 183 US trial participants, 89 % (n = 163) matched OPTN records exactly; the remainder were matched by extending agreement windows for transplant and birthdates. Matches were validated by donor and recipient blood types. By Kaplan-Meier analysis, 10 years post-transplant, freedom from acute rejection, graft failure, or death was 32.6 % and 24.0 % in the rATG and basiliximab arms, respectively (P = 0.09). The incidence of acute rejection with rATG versus basiliximab induction was 21.0 % versus 32.8 % (P = 0.07). Patient survival (52.8 % [Corrected] versus 52.2 %, P = 0.92) and graft survival (34.3 % versus 30.9 %, P = 0.56) rates were numerically and statistically similar for both arms. Comparison of the composite outcome meets non-inferiority criteria even with a 0 % equivalence margin (one sided P = 0.04). With a 10 % equivalence margin, the odds that rATG is no worse than basiliximab for 10-year risk of the composite endpoint are >99 %. CONCLUSIONS: Ten years post-transplant, rATG induction has comparable efficacy and safety to FDA-approved basiliximab. Integration of clinical trial records with national registry data can enable long-term monitoring of trial participants in transplantation, circumventing logistical and cost barriers of extended follow up. TRIAL REGISTRATION: ClinicalTrials.gov NCT00235300. PMID- 26285696 TI - Markers of iron status are associated with stage of pregnancy and acute-phase response, but not with parity among pregnant women in Guinea-Bissau. AB - While prenatal Fe supplementation prevents maternal Fe deficiency and anaemia, it is uncertain whether it improves infant health outcomes, at least when taken by Fe-replete women. Inflammation as well as physiological changes complicates the assessment of Fe status during pregnancy. In the present study, we measured the concentrations of serum ferritin and soluble transferrin receptors (sTfR), Hb and the acute-phase proteins C-reactive protein (CRP) and alpha1-antichymotrypsin (ACT) in a cross-sectional study among 738 pregnant women attending antenatal care in Guinea-Bissau, West Africa. Multiple linear regression analysis was used to identify the predictors of Fe status markers. The mean gestational age was 23 (sd 7) weeks. Serum ferritin values were lower with progressing gestation, from 27% lower during weeks 16-20 of gestation up to 59% lower after 29 weeks of gestation compared with early pregnancy. Using cut-off values for Fe deficiency as established in non-pregnant individuals, 52% of the women had sTfR levels >2.3 mg/l, while only 25% had serum ferritin levels 2.3 mg/l decreased to 47% after adjustment for elevated serum CRP and ACT levels. On the contrary, the proportion of serum ferritin < 12 MUg/l increased to 33% after adjustment for ACT and CRP. The high proportion of elevated serum sTfR calls for pregnancy-specific cut-offs since increased erythropoiesis is expected in response to increased plasma volume of pregnancy. The present study further underlines the need to adjust for inflammation when serum sTfR and serum ferritin are used to assess Fe status in pregnancy. PMID- 26285698 TI - Identification of new biomarkers for Acute Respiratory Distress Syndrome by expression-based genome-wide association study. AB - BACKGROUND: Accumulated to-date gene microarray data on Acute Respiratory Distress Syndrome (ARDS) in the Gene Expression Omnibus (GEO) represent a rich source for identifying new unsuspected targets and mechanisms of ARDS. The recently developed expression-based genome-wide association study (eGWAS) for analysis of GEO data was successfully used for analysis of gene expression of comparatively noncomplex adipose tissue, 75 % of which is represented by adipocytes. Although lung tissue is more heterogenic and does not possess a prevalent cell type for driving gene expression patterns, we hypothesized that eGWAS of ARDS samples will generate biologically meaningful results. METHODS: The eGWAS was conducted according to (Proc Natl Acad Sci U S A 109:7049-7054, 2012) and genes were ranked according to p values of chi-square test. RESULTS: The search of GEO retrieved 487 ARDS related entries. These entries were filtered for multiple qualitative and quantitative conditions and 219 samples were selected: mouse n sham/ARDS = 67/92, rat n = 13/13, human cells n = 11/11, canine n = 6/6 with the following ARDS model distributions: mechanical ventilation (MV)/cyclic stretch n = 11; endotoxin (LPS) treatment n = 8; MV + LPS n = 3; distant organ injury induced ARDS n = 3; chemically induced ARDS n = 2; Staphylococcus aureus induced ARDS n = 2; and one experiment each for radiation and shock induced ARDS. The eGWAS of this dataset identified 42 significant (Bonferroni threshold P < 1.55 * 10(-6)) genes. 66.6 % of these genes, were associated previously with lung injury and include the well known ARDS genes such as IL1R2 (P = 4.42 * 10(-19)), IL1beta (P = 3.38 * 10(-17)), PAI1 (P = 9.59 * 10(-14)), IL6 (P = 3.57 * 10( 12)), SOCS3 (P = 1.05 * 10(-10)), and THBS1 (P = 2.01 * 10(-9)). The remaining genes were new ARDS candidates. Expression of the most prominently upregulated genes, CLEC4E (P = 4.46 * 10(-14)) and CD300LF (P = 2.31 * 10(-16)), was confirmed by real time PCR. The former was also validated by in silico pathway analysis and the latter by Western blot analysis. CONCLUSIONS: Our first in the field application of eGWAS in ARDS and utilization of more than 120 publicly available microarray samples of ARDS not only justified applicability of eGWAS to complex lung tissue, but also discovered 14 new candidate genes which associated with ARDS. Detailed studies of these new candidates might lead to identification of unsuspected evolutionarily conserved mechanisms triggered by ARDS. PMID- 26285697 TI - Gene expression during zombie ant biting behavior reflects the complexity underlying fungal parasitic behavioral manipulation. AB - BACKGROUND: Adaptive manipulation of animal behavior by parasites functions to increase parasite transmission through changes in host behavior. These changes can range from slight alterations in existing behaviors of the host to the establishment of wholly novel behaviors. The biting behavior observed in Carpenter ants infected by the specialized fungus Ophiocordyceps unilateralis s.l. is an example of the latter. Though parasitic manipulation of host behavior is generally assumed to be due to the parasite's gene expression, few studies have set out to test this. RESULTS: We experimentally infected Carpenter ants to collect tissue from both parasite and host during the time period when manipulated biting behavior is experienced. Upon observation of synchronized biting, samples were collected and subjected to mixed RNA-Seq analysis. We also sequenced and annotated the O. unilateralis s.l. genome as a reference for the fungal sequencing reads. CONCLUSIONS: Our mixed transcriptomics approach, together with a comparative genomics study, shows that the majority of the fungal genes that are up-regulated during manipulated biting behavior are unique to the O. unilateralis s.l. genome. This study furthermore reveals that the fungal parasite might be regulating immune- and neuronal stress responses in the host during manipulated biting, as well as impairing its chemosensory communication and causing apoptosis. Moreover, we found genes up-regulated during manipulation that putatively encode for proteins with reported effects on behavioral outputs, proteins involved in various neuropathologies and proteins involved in the biosynthesis of secondary metabolites such as alkaloids. PMID- 26285700 TI - Directly observed treatment short-course (DOTS) for treatment of new tuberculosis cases in Somali Regional State, Eastern Ethiopia: ten years retrospective study. AB - BACKGROUND: A third of the world population is infected with tuberculosis (TB) bacilli. TB accounts for 25% of all avoidable deaths in developing countries. The objective of the study was to assess impact of directly observed treatment short course (DOTS) strategy on new tuberculosis case finding and treatment outcomes in Somali Regional State, Ethiopia from 2003 up to 2012 and from 2004 up to 2013, respectively. METHODS: A health facility based retrospective study was employed. Quarterly reports were collected using World Health Organization (WHO) reporting format for TB case finding and treatment outcome from all zones in the region to the Federal Ministry of Health. RESULTS: A total of 31, 198 all types of new TB cases were registered and reported during the period from 2003 up to 2012, in the region. Out of these, smear positive pulmonary TB cases were 12,466 (40%), and 10,537 (33.8%) and 8195 (26.2%) for smear negative pulmonary TB and extra pulmonary TB cases, respectively. An average case detection rate (CDR) of 19.1% (SD 3.6) and treatment success rate (TSR) of 85.5% (SD 5.0) for smear positive pulmonary TB were reported for the specified years period. For the overall study period, trend chi-squire analysis for CDR was X(2) = 2.1; P > 0.05 and X(2) = 5.64; P < 0.05 for TSR. CONCLUSIONS: The recommended TSR set by WHO was achieved (85.5%) and the CDR reported was far below (19.1%) from the recommended target. Extensive efforts should be established to maintain the achieved TSR and to increase the low CDR for the smear positive pulmonary TB cases through implementing alternative case finding strategies. PMID- 26285699 TI - Major decrease in malaria transmission on Mayotte Island. AB - BACKGROUND: Plasmodium falciparum is responsible for most malaria cases on Mayotte Island, in the Comorian Archipelago. Malaria is endemic and a major public health problem in the archipelago with an intense, stable and permanent transmission. This study reports results of 8 years of malaria surveillance from 2007 to 2014 after the strengthening of malaria control activities in Mayotte and the neighbouring islands. METHODS: Surveillance was based on physicians' reports of malaria cases between January 2007 and December 2014. Malaria cases were confirmed by at least a positive rapid diagnostic test and/or demonstration of Plasmodium sp. in a blood smear. The date, and the patients' age, sex, address, presentation of symptoms, biology, treatment and recent history of travel were collected by verbal questioning during consultation and/or hospitalization. Monthly rainfall data were also compiled during the study period. RESULTS: From 2007 to 2014, 2073 cases were reported on Mayotte Island: 977 imported cases, 807 autochthonous cases and 289 cases of unknown origin. The total malaria annual parasite incidence lowered from 3.0 in 2007 to 0.07 per 1,000 inhabitants in 2014 as the autochthonous malaria incidence decreased from 1.6 to 0.004 per 1,000 inhabitants in the same period and in all age groups. Most of the imported cases came from Comoros (94 %). Severe forms represented approximately 11 % of cases, and only two deaths have been recorded among the imported cases. Approximately 19 % of cases were hospitalized (3 % in an intensive care unit). There is clearly a decrease in malaria transmission in Mayotte since 2007 and the goal of elimination seems more achievable than ever. In 2011, Mayotte entered the elimination phase when P. falciparum API passed under 1 case per 1,000 people at risk. CONCLUSIONS: The combination of vector control measures, active surveillance and case management, including effective treatment with artemisinin based combination therapy, has been essential to achieve a present status of low and decreasing malaria transmission on the island. Mayotte has entered the elimination phase, but some goals remain to be accomplished before a programme re orientation toward malaria elimination is contemplated. Moreover, a regional management policy is crucial because this would allow control measures to be targeted and based on a regional surveillance-response system rather than isolated. PMID- 26285701 TI - Musculoskeletal symptoms in an adolescent athlete population: a comparative study. AB - BACKGROUND: Musculoskeletal pain, symptoms or injuries are prevalent in the adolescent athlete population as well as in the general adolescent population, and often have significant consequences on their future musculoskeletal health. However, differences between these two populations in regards to their musculoskeletal health are not known and have not yet been explored. Therefore, the main objectives of this study are to 1) compare the 6-month prevalence of musculoskeletal symptoms and their impact on school attendance and reduction in sport or leisure activity between a group of adolescent athletes and a group of control adolescents, and 2) determine if gender has different effects on the prevalence of musculoskeletal symptoms in these two populations. METHODS: Among adolescents who participated in the 2012 Quebec summer games, 1,865 agreed to participate and constituted the adolescent athletes group (mean age:14.12 +/- 1.22). An additional cohort of 707 adolescents from two schools was also recruited to form the comparison control group (mean age: 14.69 +/- 1.38). Anthropometric data were collected, and the musculoskeletal 6-month prevalence of symptoms and their related impacts were assessed using the Teen Nordic Musculoskeletal Screening Questionnaire (TNMQ-S). Participants' characteristics as well as symptoms prevalence for the nine anatomical regions as well as their impact on school/work absence and reduction in physical/leisure activities were compared between athletes and control adolescents. RESULTS: When compared to athlete adolescents, significantly more controls had a positive 6-month prevalence of symptoms affecting the neck (48.8% vs 26.3%), upper back (41.3% vs 18.1%) and low back (45.4% vs 35.8%) when compared to athlete. Symptoms affecting the spine led to significantly more school absence and reduction in physical activity in the control group. Controls also showed higher prevalence of shoulder (37.1% vs 28.3%) and wrist/hand (23.8% vs 17.4%) symptoms, while athletes had a higher prevalence of elbow symptoms (8.7% vs 11.4%). CONCLUSION: Despite their higher risk of injuries related to high levels of competition or sport participation, adolescent athletes have fewer symptoms affecting the spine than "typical adolescents", and similar prevalence of symptoms affecting the body's extremities. Further investigations are necessary to understand the differences between athletes and non-athletes in regard to disability and long-term complications associated to musculoskeletal pain or symptoms. PMID- 26285702 TI - Improved coverage and timing of childhood vaccinations in two post-Soviet countries, Armenia and Kyrgyzstan. AB - BACKGROUND: Timing of childhood vaccinations has received close attention in many countries. Little is known about the trends in correctly timed vaccination in former Soviet countries. We examined trends in vaccination coverage and correct timing of vaccination in two post-Soviet countries, Armenia and Kyrgyzstan, and analyzed factors associated with delayed vaccinations. METHODS: We used data from the Demographic and Health Surveys; the surveys were conducted in 2000 (n = 1726), 2005 (n = 1430) and 2010 (n = 1473) in Armenia and in 1997 (n = 1127) and 2012 (n = 4363) in Kyrgyzstan. We applied the Kaplan-Meier method to estimate age specific vaccination coverage with diphtheria, tetanus and pertussis (DTP) vaccine and a measles-containing vaccine (MCV). A Cox proportional hazard regression with shared frailty was used to examine factors associated with delayed vaccinations. RESULTS: Vaccination coverage for all three doses of the DTP vaccine increased in Armenia from 92 % in 2000 to 96 % in 2010. In Kyrgyzstan, DTP coverage was 96 % and 97 % in 1997 and 2012, respectively. Vaccination coverage for MCV increased from 89 % (Armenia, 2000) and 93 % (Kyrgyzstan, 1997) to 97 % (Armenia, 2010) and 98 % (Kyrgyzstan, 2012). The proportion of children with correctly timed vaccinations increased over time for all examined vaccinations in both countries. For example, the proportion of children in Armenia with correctly timed first DTP dose (DTP1) increased from 46 % (2000) to 66 % (2010). In Kyrgyzstan, the proportion of correctly timed DTP1 increased from 75 % (1997) to 87 % (2012). In Armenia, delays in the third DTP dose (DTP3) and MCV vaccinations were less likely to occur in the capital, whereas in Kyrgyzstan DTP3 and MCV start was delayed in the capital compared to other regions of the country. Also, in Armenia living in urban areas was associated with delayed vaccinations. CONCLUSIONS: Vaccination coverage and timing of vaccination improved over the last years in both countries. Further efforts are needed to reduce regional differences in timely vaccinations. PMID- 26285703 TI - Does obesity have detrimental effects on IVF treatment outcomes? AB - BACKGROUND: The aim of this study was to investigate the influence of body mass index (BMI) on the in vitro fertilization (IVF) treatment outcomes in a cohort of women undergoing their first IVF, using an intracytoplasmic sperm injection (ICSI). METHODS: This retrospective cohort study included 298 cycles from women younger than 38 years old undergoing IVF-ICSI at a university infertility clinic. The treatment cycles were divided into three groups according to the BMI of the women involved: normal weight (18.5 <= BMI < 25 kg/m(2), 164 cycles), overweight (25 <= BMI < 30 kg/m(2), 70 cycles), and obese (BMI >= 30 kg/m(2), 64 cycles). The underweight women (BMI < 18.5 kg/m(2)) were not included in the analysis due to small sample size (n = 22). The patient characteristics and IVF-ICSI treatment outcomes were compared between the BMI groups. RESULTS: The total gonadotropin dose (p <0.001) and duration of stimulation (p = 0.008) were significantly higher in the obese group when compared to the normal BMI group. There were no significant differences across the BMI categories for the other IVF-ICSI cycle outcomes measured, including the number of retrieved oocytes, mature oocytes, embryos suitable for transfer, proportion of oocytes fertilized, and cycle cancellation rates (p >0.05 for each). Additionally, clinical pregnancy, spontaneous abortion, and the ongoing pregnancy rates per transfer were found to be comparable between the normal weight, overweight, and obese women (p >0.05 for each). CONCLUSION: Obese women might require a significantly higher dose of gonadotropins and longer stimulation durations, without greatly affecting the pregnancy outcomes. PMID- 26285704 TI - The effect of standard dose multivitamin supplementation on disease progression in HIV-infected adults initiating HAART: a randomized double blind placebo controlled trial in Uganda. AB - BACKGROUND: Efficacy trials investigating the effect of multivitamin (MV) supplementations among patients on Highly Active Antiretroviral Therapy (HAART) have so far been inconclusive. We conducted a randomized, double blind, placebo controlled trial to determine the effect of one recommended daily allowance (RDA) of MV supplementation on disease progression in patients initiating HAART. METHODS: Eligible subjects were randomized to receive placebo or MV supplementation including vitamins B-complex, C and E. Participants were followed for up to 18 months. Primary endpoints were: change in CD4 cell count, weight and quality of life (QoL). Secondary endpoints were: i) development of a new or recurrent HIV disease progression event, including all-cause mortality; ii) switching from first- to second-line antiretroviral therapy (ART); and iii) occurrence of an adverse event. Intent-to-treat analysis, using linear regression mixed effects models were used to compare changes over time in the primary endpoints between the study arms. Kaplan-Meier time-to-event analysis and the log rank test was used to compare HIV disease progression events and all-cause mortality. RESULTS: Four hundred participants were randomized, 200 onto MV and 200 onto placebo. By month 18, the average change in CD4 cell count in the MV arm was 141 cells/uL compared to 147 cells/uL in the placebo arm, a mean difference of -6 . 17 [95 % CI -29 . 3, 16 . 9]. The average change in weight in the MV arm was 3 . 9 kg compared to 3 . 3 kg in the placebo arm, a mean difference of 0 . 54 [95 % CI -0 . 40, 1 . 48]; whereas average change in QoL scores in the MV arm was 6 . 8 compared to 8 . 8 in the placebo arm, a mean difference of -2.16 [95 % CI 4 . 59,0 . 27]. No significant differences were observed in these primary endpoints, or in occurrence of adverse events between the trial arms. CONCLUSIONS: One RDA of MV supplementation was safe but did not have an effect on indicators of disease progression among HIV infected adults initiating HAART. TRIAL REGISTRATION: Clinical trials NCT01228578 , registered on 15th October 2010. PMID- 26285705 TI - Genetic variations of MUC17 are associated with endometriosis development and related infertility. AB - BACKGROUND: Genetic alterations of mucin genes, such as MUC2 and MUC4, were previously identified to be associated with endometriosis and related infertility. Additionally, gene expression profiling has confirmed MUC17 to be overexpressed in mucinous ovarian carcinoma; however, its associated risk for endometriosis remains unclear. This study was focused on the potential impact of genetic variations in MUC17 on endometriosis development and associated clinical features. METHODS: The study subjects included 189 female Taiwanese patients with pathology-proven endometriosis and 191 healthy Taiwanese women as controls. Five single-nucleotide polymorphisms (rs4729645, rs10953316, rs74974199, rs4729655, and rs4729656) within the MUC17 gene were selected and genotyped using the Taqman genotyping assay to examine the allele frequency and genotype distributions of MUC17 polymorphisms. RESULTS: Genotyping revealed that the A allele at rs10953316 in MUC17 was a protective genetic factor in endometriosis development (p = 0.008; OR = 0.53; 95% CI: 0.36-0.79). Genetic variation of rs4729655 protected patients against endometriosis-induced infertility, but was associated with a higher cancer antigen 125 (CA125) level. Base-pairing analysis, called MaxExpect, predicted an additional loop in the mRNA structure caused by rs10953316 polymorphism, possibly influencing ribosome sliding and translation efficiency. Such predictions were confirmed by immunohistochemistry that patients with AA genotype at rs10953316 showed low MUC17 levels in their endometrium, patients with GA genotype showed moderate levels, and strong staining could be found in patients with GG genotype. CONCLUSIONS: MUC17 polymorphisms are involved in endometriosis development and the associated infertility in the Taiwanese population. PMID- 26285706 TI - Intra-esophageal whitish mass - a challenging diagnosis. AB - BACKGROUND: Whitish intraluminal esophageal masses might represent the endoscopic feature of a bezoar or a pedunculated tumor, most likely a fibrovascular polyp, without exclusion of other mesenchymal tumors (leiomyoma, lipoma, gastrointestinal stromal tumor, leiomyosarcoma, granular cell tumor). If a process of dystrophic calcification is also encountered the differential diagnosis can be a challenge even after histological analysis, as it is highlighted by our case. CASE PRESENTATION: A 65-year-old female whom took lactate calcium tablets for 5 years presented with progressive dysphagia. A whitish esophageal mass with an appearance of a pharmacobezoar was detected at esophagoscopy. A pedunculated tumor was considered in the differential diagnosis, but the imagistic studies ruled out a pedicle. This intraluminal esophageal mass highly suggestive for a pharmacobezoar was endoscopically removed. The challenge of correct diagnosis was raised by histological examination performed after immersion into trichloracetic acid for decalcification. The identification of hyaline fibrous tissue, with numerous crystalline basophils deposits of minerals, rare fibrocytes and very few vessels brought in discussion a mesenchymal originating mass, most likely a fibrovascular polyp, even the pedicle was not detected. CONCLUSION: Based on our challenging and difficult to diagnose case we proposed an uncommon evolution: auto-amputation and calcification of an esophageal mesenchymal originating tumor (most likely a fibrovascular polyp). PMID- 26285708 TI - Plan and road map for health reform in Iran. PMID- 26285707 TI - Study of acute transfusion reactions in a teaching hospital of Sikkim: A hemovigilance initiative. AB - OBJECTIVE: Blood transfusions are inherently associated with risks ranging in severity from minor to life-threatening. Continuous monitoring of transfusion related complications can promote understanding of factors contributing to transfusion reactions and help to formulate necessary remedial measures. This study was designed to analyze the frequency and nature of transfusion reactions reported to the blood bank of a remote North East Indian teaching hospital. MATERIALS AND METHODS: All acute transfusion reactions (ATRs) reported to the blood bank over a period of 20 months (May 2013 to January 2015) were reviewed and analyzed. The risk of transfusion reactions associated with each individual component was assessed. RESULTS: A total of 3455 units of whole blood and component transfusions were carried out of which a total of 32 (0.92%) ATRs were encountered. Packed red blood cells (PRBCs) (n = 15, P = 0.06) and whole blood (WB) (n = 13, P = 0.83) were most commonly implicated. Allergic reaction was the most frequent transfusion reaction encountered (65.6%), seen most commonly with PRBC (risk of 0.76%, P = 0.42), and WB (risk of 0.68%, P = 0.63) transfusions. This was followed by febrile reactions (28.1%), which were seen more commonly with PRBCs (risk of 0.57%, P = 0.016). No reactions were observed with platelet transfusions. CONCLUSION: The overall incidence of transfusion reactions in this hospital is slightly higher than those having more advanced transfusion facilities in India. The lack of leukoreduction facilities in our hospital could be a likely cause for the same. The use of leukoreduced WB and PRBCs could possibly reduce the overall incidence of ATRs in general and febrile nonhemolytic transfusion reactions in particular. PMID- 26285709 TI - Different functional modes of BAR domain proteins in formation and plasticity of mammalian postsynapses. AB - A plethora of cell biological processes involve modulations of cellular membranes. By using extended lipid-binding interfaces, some proteins have the power to shape membranes by attaching to them. Among such membrane shapers, the superfamily of Bin-Amphiphysin-Rvs (BAR) domain proteins has recently taken center stage. Extensive structural work on BAR domains has revealed a common curved fold that can serve as an extended membrane-binding interface to modulate membrane topologies and has allowed the grouping of the BAR domain superfamily into subfamilies with structurally slightly distinct BAR domain subtypes (N-BAR, BAR, F-BAR and I-BAR). Most BAR superfamily members are expressed in the mammalian nervous system. Neurons are elaborately shaped and highly compartmentalized cells. Therefore, analyses of synapse formation and of postsynaptic reorganization processes (synaptic plasticity) - a basis for learning and memory formation - has unveiled important physiological functions of BAR domain superfamily members. These recent advances, furthermore, have revealed that the functions of BAR domain proteins include different aspects. These functions are influenced by the often complex domain organization of BAR domain proteins. In this Commentary, we review these recent insights and propose to classify BAR domain protein functions into (1) membrane shaping, (2) physical integration, (3) action through signaling components, and (4) suppression of other BAR domain functions. PMID- 26285710 TI - Don't forget hand care when promoting hand hygiene in hospitals. PMID- 26285711 TI - Correction and Addition to "Tuning Metal-Organic Frameworks with Open-Metal Sites and Its Origin for Enhancing CO2 Affinity by Metal Substitution". PMID- 26285712 TI - Artificial Spectrin Shells Reconstituted on Giant Vesicles. AB - In the experimental approach to a synthetic minimal cell, the membrane compartment is a main component. Lipid vesicles represent the natural host for the artificial reconstruction of a cytomimetic membrane skeleton able to support mechanical function. Using the membrane component of human erythroid cells, we have reconstructed a membrane shell composed of a spectrin skeleton and fed by ATP. The structural and mechanical analysis reveals this spectrin skeleton as topological network supporting mechanical rigidity. Such an artificial shell would define a membrane compartment mechanically stable under physiological conditions. PMID- 26285713 TI - Reduced Water Density in a Poly(ethylene oxide) Brush. AB - A model poly(ethylene oxide) (PEO) brush system, prepared by spreading a poly(ethylene oxide)-poly(n-butyl acrylate) (PEO-PnBA) amphiphilic diblock copolymer onto an air-water interface, was investigated under various grafting density conditions by using the X-ray reflectivity (XR) technique. The overall electron density profiles of the PEO-PnBA monolayer in the direction normal to the air-water interface were determined from the XR data. From this analysis, it was found that inside of the PEO brush, the water density is significantly lower than that of bulk water, in particular, in the region close to the PnBA-water interface. Separate XR measurements with a PnBA homopolymer monolayer confirm that the reduced water density within the PEO-PnBA monolayer is not due to unfavorable contacts between the PnBA surface and water. The above result, therefore, lends support to the notion that PEO chains provide a hydrophobic environment for the surrounding water molecules when they exist as polymer brush chains. PMID- 26285714 TI - Thioflavin T Promotes Abeta(1-40) Amyloid Fibrils Formation. AB - Fibrillogenesis of the small peptide Abeta(1-40) is considered to be the hallmark of Alzheimer's disease. Some evidence indicates small oligomers, rather than mature fibrils, as the key cytotoxic agents. The fluorescent dye Thioflavin T (ThT) is often used to detect amyloid deposits in both in vivo and in vitro experiments, and it is used to study kinetic measurements, under the fundamental hypothesis that this probe does not influence the aggregation processes. We report experimental data showing that ThT may promote the Abeta(1-40) peptide amyloid aggregation changing solvent-peptide interactions and stabilizing more ordered beta-like conformation. This finding has a two-fold importance: It is a fundamental warning in all fibrillation experiments where ThT is used as fluorescent probe, and it suggests that ThT, accelerating fibril formation, could be used to reduce the presence of transient small oligomers, thus interfering with the pathogenic impact of Abeta peptide. PMID- 26285715 TI - Crystal Nucleation without Supersaturation. AB - Classical nucleation theory (CNT) has been extensively employed to interpret crystal nucleation phenomena and postulates the formation of an ordered crystalline nucleus directly from vapor or solution. Here, we provide the first experimental demonstration of a two-step mechanism that facilitates deposition of crystals on solid surfaces from vapor. Crucially, this occurs from saturated vapor without the need for supersaturation, conditions that, according to CNT, cannot lead to direct deposition of crystals from vapor. Instead, the process relies on condensation of supercooled liquid in surface cavities below the melting point. Crystals then nucleate in this liquid, leading to rapid deposition of more solid. Such a mechanism has been postulated for atmospheric nucleation of ice on aerosol particles and may have analogies in the crystallization of biominerals via amorphous precursor phases. PMID- 26285716 TI - Functionalization of Graphene Oxide with Polyhedral Oligomeric Silsesquioxane (POSS) for Multifunctional Applications. AB - Through the amide formation between amine-functionalized polyhedral oligomeric silsesquioxane (POSS) and oxygen-containing groups (e.g., epoxy and carboxyl groups) in graphene oxide (GO), we have synthesized POSS-functionalized graphene nanosheets (POSS-graphene), which are highly soluble in various organic solvents attractive for multifunctional applications. Thin films from solution casting of the resultant POSS-graphene were found to show superhydrophobic properties with a water/air contact angle of ~157 degrees , while the superhydrophobic POSS graphene powder could be used to construct liquid marbles. In addition, the POSS graphene hybrids were also used as novel nanofillers to increase the glass transition temperature (Tg) and decompose temperature (Td) for polymers. PMID- 26285717 TI - Water Desalination with Wires. AB - We show the significant potential of water desalination using a novel capacitive wire-based technology in which anode/cathode wire pairs are constructed from coating a thin porous carbon electrode layer on top of electrically conducting rods (or wires). By alternately dipping an array of electrode pairs in freshwater with and in brine without an applied cell voltage, we create an ion adsorption/desorption cycle. We show experimentally how in six subsequent cycles we can reduce the salinity of 20 mM feed (brackish) water by a factor of 3, while application of a cation exchange membrane on the cathode wires makes the desalination factor increase to 4. Theoretical modeling rationalizes the experimental findings, and predicts that system performance can be significantly enhanced by material modifications. To treat large volumes of water, multiple stacks of wire pairs can be used simultaneously in a "merry-go-round" operational mode. PMID- 26285718 TI - Synthesis and the Origin of the Stability of Thiolate-Protected Au130 and Au187 Clusters. AB - Two stable thiolate-protected gold clusters (Au-SR), Au130 and Au187 clusters, were synthesized to obtain a better understanding of the size dependence of the origin of the stability of Au-SR clusters. These clusters were synthesized by employing different preparation conditions from those used to synthesize previously reported magic gold clusters; in particular, a lower [RSH] to [AuCl4( )] molar ratio ([AuCl4(-)]/[RSH] = 1:1) was used than that used to prepare Au25(SR)18, Au38(SR)24, Au68(SR)34, Au102(SR)44, and Au144(SR)60 (id. = 1:4-12). The two clusters thus synthesized were separated from the mixture by high performance liquid chromatography with reverse-phase columns. Mass spectrometry of the products revealed the presence of two clusters with chemical compositions of Au130(SC12H25)50 and Au187(SC12H25)68. The origin of the stability of these two clusters and the size dependence of the origin of the stability of thiolate protected gold clusters were discussed in terms of the total number of valence electrons. PMID- 26285719 TI - Analysis of the Origin of Open Circuit Voltage in Dye Solar Cells. AB - Changes in the composition of the electrolyte are known to affect the parameters that determine the performance of dye solar cells. This paper describes a robust method for the analysis of the photovoltage in dye solar cells. The method focuses on the study of recombination resistance and chemical capacitance of TiO2 obtained from impedance spectroscopy. Four dye solar cells with electrolytes producing known effects on photovoltage behavior have been studied. Effects of conduction band shifts and changes in recombination rate in the photovoltage have been evaluated quantitatively. PMID- 26285720 TI - Ultrafast Photoinduced Dynamics at Air/Liquid and Liquid/Liquid Interfaces. AB - Although liquid/liquid and air/liquid interfaces are omnipresent, very little is known up to now about the dynamics of processes occurring at such interfaces. As a detailed understanding of these processes could be of invaluable technological, environmental, and medical importance, considerable effort has been invested over the last two decades in developing new interface-selective techniques that allow for gaining further insight into the dynamics of these processes. Whereas several major results have been achieved that helped to contribute to a deeper understanding, there are still many aspects concerning the properties of liquid interfaces that are not yet fully understood. In this Perspective, the work that has been carried out so far on photoinduced interfacial dynamics will be reviewed and the current challenges in this still emerging field of research discussed. PMID- 26285721 TI - Correction to "Catalytic Activity of Pd/Cu Random Alloy Nanoparticles for Oxygen Reduction". PMID- 26285722 TI - Non-Ergodic Electron Transfer in Mixed-Valence Charge-Transfer Complexes. AB - Theories of activated transitions traditionally separate the dynamics and statistics of the thermal bath in the reaction rate into the preexponential frequency factor for the dynamics and a Boltzmann factor for the statistics. When the reaction rate is comparable to relaxation frequencies of the medium, the statistics loses ergodicity and the activation barrier becomes dependent on the medium dynamics. This scenario is realized for mixed-valence self-exchange electron transfer at temperatures near the point of solvent crystallization. These complexes, studied by Kubiak and coworkers, display anti-Arrhenius temperature dependence on lowering temperature when approaching crystallization; that is, the reaction rate increases nonlinearly in Arrhenius coordinates. Accordingly, the solvent relaxation slows down following a power temperature law. With this functional form for the relaxation time, nonergodic reaction kinetics accounts well for the observations. PMID- 26285723 TI - Epitaxial Heterostructures of Lead Selenide Quantum Dots on Hematite Nanowires. AB - We present a novel method for synthesizing epitaxial quantum dot-nanowire (QD-NW) heterostructures using the example of colloidal PbSe QDs decorated on furnace grown hematite (alpha-Fe2O3) NWs. The direct heterogeneous nucleation of QDs on Fe2O3 NWs relies upon an aggressive surface dehydration of the as-synthesized Fe2O3 NWs at 350 degrees C under vacuum and subsequent introduction of colloidal reactants resulting in direct growth of PbSe QDs on Fe2O3. The synthesis is tunable: the QD diameter distribution and density of QDs on the NWs increase with increased dehydration time, and QD diameters and size distributions decrease with decreased injection temperature of the colloidal synthesis. Transmission electron microscopy (TEM) structural analysis reveals direct heteroepitaxial heterojunctions where the matching faces can be PbSe (002) and Fe2O3 (003) with their respective [110] crystallographic directions aligned. This can be a general approach for integrating colloidal and furnace synthetic techniques, thus broadening possible material combinations for future high-quality, epitaxial nanoscale heterostructures for solar applications. PMID- 26285724 TI - Ionic Vapor: What Does It Consist Of? AB - A comprehensive description of room-temperature ionic liquids (RTILs) requires characterization of their properties around normal boiling and critical. Using a thoroughly parametrized force field, we report atomistic simulations of the vapor phase of N-butylpyridinium tetrafluoroborate and 1-ethyl-3-methylimidazolium bis(trifluoromethanesulphonyl)amide, existing in equilibrium with the liquid phase. We show that in contrast to traditional gases comprised of one type of molecules, the saturated vapor of RTILs consists of a broad range of structures, involving both neutral and charged species. While typically the ionic pair is the most stable vapor structure, the species distribution depends on RTIL chemical composition and is sensitive to temperature and pressure. PMID- 26285725 TI - Optical Properties of Mn-Doped ZnTe Magic Size Nanocrystals. AB - In this letter we report successful doping of ZnTe magic size nanocrystals (MSNCs) with Mn(2+). Colloidal ZnTe MSNCs are prepared via a hot-injection method and doped with Mn(2+) via cation exchange. The doped MSNCs show an emission band centered at 620 nm with a radiative decay time of 45 MUs, characteristic of Mn(2+) in ZnTe. The excitation spectrum of the Mn(2+) emission shows narrow absorption bands corresponding to different sizes of ZnTe MSNCs providing further evidence that the 620 nm emission originates from Mn(2+) incorporated in the ZnTe host, rather than Mn(2+) bound to the surface. The Mn(2+)-doped ZnTe clusters may serve as nuclei for the growth of larger ZnTe quantum dots doped with a single Mn(2+) ion. PMID- 26285726 TI - Rational Development of Ternary Alloy Electrocatalysts. AB - Improving the efficiency of electrocatalytic reduction of oxygen represents one of the main challenges for the development of renewable energy technologies. Here, we report the systematic evaluation of Pt-ternary alloys (Pt3(MN)1 with M, N = Fe, Co, or Ni) as electrocatalysts for the oxygen reduction reaction (ORR). We first studied the ternary systems on extended surfaces of polycrystalline thin films to establish the trend of electrocatalytic activities and then applied this knowledge to synthesize ternary alloy nanocatalysts by a solvothermal approach. This study demonstrates that the ternary alloy catalysts can be compelling systems for further advancement of ORR electrocatalysis, reaching higher catalytic activities than bimetallic Pt alloys and improvement factors of up to 4 versus monometallic Pt. PMID- 26285727 TI - Probing Inter- and Intrachain Exciton Coupling in Isolated Poly(3-hexylthiophene) Nanofibers: Effect of Solvation and Regioregularity. AB - We report wavelength and time-resolved photoluminescence studies of isolated extended (1-10 MUm length) poly(3-hexylthiophene) (P3HT) nanofibers (xNFs) cast on glass from suspension. The PL spectra of xNFs show multiple vibronic replicas that appear to be associated with the existence of both H- and J-type aggregates. The PL spectra of xNFs made from regioregular (rr)- (93%) and highly regioregular (hrr)-P3HT (98%) both show similarities in PL spectra suggestive of common chain packing features, as well as subtle differences that can be attributed to higher long-range order in the hrr-xNFs. Specifically, PL spectral measurements on isolated xNFs made from highly regioregular (>98%) P3HT showed a red-shifted electronic origin (~30 meV) and increased 0-0/0-1 PL intensity ratio for the J type species, suggestive of enhanced structural coherence length and intrachain order. PMID- 26285728 TI - Reaction of the Basal Plane of Graphite with the Methyl Radical. AB - The reaction of methyl radicals with the basal plane of graphite has been observed to occur with an activation energy of less than 0.3 eV. This reaction is initiated by Li-induced CH3Cl dissociation to produce CH3 radicals on the graphite surface. It is found that ~3/4 of the methyl radicals remain on the graphite surface up to 700 K at puckered sp(3) carbon sites, while 1/4 of the CH3 radicals participate in CH4 formation and small amounts of C2 and C3 hydrocarbon formation. CH3 radicals become mobile over an activation energy barrier of ~0.7 eV. PMID- 26285729 TI - Probing Electron-Transfer Times in Photosynthetic Reaction Centers by Hole Burning Spectroscopy. AB - A brief discussion is presented of transient hole-burned (HB) spectra (and the information that they provide) obtained for isolated reaction centers (RCs) from wild-type (WT) Rhodobacter sphaeroides, RCs containing zinc-bacteriochlorophylls (Zn-BChls), and RCs of Photosystem II (PSII) from spinach and Chlamydomonas reinhardtii . The shape of the spectral density and the strength of electron phonon coupling in bacterial RCs are discussed. We focus, however, on heterogeneity of isolated PS II RCs from spinach and, in particular, Chlamydomonas reinhardtii , site energies of active (electron acceptor) and inactive pheophytins, the nature of the primary electron donor(s), and the possibility of multiple charge-separation (CS) pathways in the isolated PSII RC. We conclude with comments on current efforts in HB spectroscopy in the area of photosynthesis and future directions in HB spectroscopy. PMID- 26285730 TI - Probing the Electronic Structure of a Photoexcited Solar Cell Dye with Transient X-ray Absorption Spectroscopy. AB - This study uses transient X-ray absorption (XA) spectroscopy and time-dependent density functional theory (TD-DFT) to directly visualize the charge density around the metal atom and the surrounding ligands following an ultrafast metal-to ligand charge-transfer (MLCT) process in the widely used Ru(II) solar cell dye, Ru(dcbpy)2(NCS)2 (termed N3). We measure the Ru L-edge XA spectra of the singlet ground ((1)A1) and the transient triplet ((3)MLCT) excited state of N3(4-) and perform TD-DFT calculations of 2p core-level excitations, which identify a unique spectral signature of the electron density on the NCS ligands. We find that the Ru 2p, Ru eg, and NCS pi* orbitals are stabilized by 2.0, 1.0, and 0.6 eV, respectively, in the transient (3)MLCT state of the dye. These results highlight the role of the NCS ligands in governing the oxidation state of the Ru center. PMID- 26285731 TI - On the Electronic Structures of Au25(SR)18 Clusters Studied by Magnetic Circular Dichroism Spectroscopy. AB - The first magnetic circular dichroism (MCD) spectra are reported at room temperature for well-defined thiolate-protected Au25 clusters (Au25(SG)18 and Au25(PET)18, where SG and PET denote glutathione and 2-phenylethanethiolate, respectively). MCD essentially corresponds to electronic transitions in the absorption spectrum, so the electronic structures of the Au25 clusters are explored based on a simultaneous deconvolution analysis of both the electronic absorption and MCD spectra, giving enhanced spectral resolution. We then find that the observed MCD responses are entirely interpreted in terms of the Faraday B terms, representing strict nondegeneracies of the excited and ground states of the Au25 clusters that correspond to so-called superatom D and P orbitals, respectively. PMID- 26285732 TI - "Light Switch" Effect Upon Binding of Ru-dppz to Water-Soluble Conjugated Polyelectrolyte Dendrimers. AB - We report the "light switch" effect of [Ru(bpy)2(dppz)](2+) (where bpy = 2,2' bipyridine and dppz = dipyrido[3,2-a:2',3'-c] phenazine, Ru-dppz) in the presence of anionic conjugated polyelectrolyte dendrimers (CPDs). The metal-to-ligand charge-transfer luminescence from Ru-dppz is efficient in the presence of CPD because the complex is shielded from water by binding to the hydrophobic dendrimer core. PMID- 26285733 TI - Helical Conjugated Polyelectrolyte Aggregation Induced by Biotin-Avidin Interaction. AB - Fluorescence correlation spectroscopy (FCS) is applied to demonstrate avidin induced cross-linking in a system consisting of a helical anionic conjugated polyelectrolyte (P1) and a biotin-tetramethylrhodamine (TMR) conjugate (2). In a previous study, we used fluorescence spectroscopy to demonstrate that 2 binds to P1 via intercalation of the TMR chromophore into the P1 helix. Addition of avidin to the P1/2 complex induces little change in the fluorescence of the system; however, FCS reveals a remarkable increase in the diffusion time of the P1/2 complex in the presence of avidin. This change is attributed to supramolecular polymer aggregates produced by cross-link formation between the biotin unit of intercalated 2 and avidin. Atomic force microscopy imaging provides evidence supporting the existence of these aggregates. The highly sensitive FCS method is used to develop a novel sensor for the biotin-avidin interaction, with a detection limit of <100 pM for avidin. PMID- 26285734 TI - Spontaneous Spectral Diffusion in CdSe Quantum Dots. AB - Spectral diffusion of the emission line of single colloidal nanocrystals is generally regarded as a random process. Here, we show that each new spectral position has a finite memory of previous spectral positions, as evidenced by persistent anticorrelations in time series of spectral jumps. The anticorrelation indicates that there is an enhanced probability of the charge distribution around the nanocrystal returning to a previous configuration. We show both statistically and directly that this memory manifests as an observable spontaneous "relaxation" in the absence of a pump laser, so that spectral diffusion progresses in a manner of "two steps forward and one step back". PMID- 26285735 TI - Photoinduced Dynamics in Membranes and at Interfaces. PMID- 26285736 TI - Structural and Entropic Allosteric Signal Transduction Strength via Correlated Motions. AB - Allosteric signal transduction in biomacromolecules can play an essential role in their function. Internal motional correlations in proteins provide a possible communication mechanism, but the quantitative relationship between statistical correlations and allostery is unknown. Quantitative relationships between internal motional correlations and the efficiency of propagation of allosteric structural and entropic effects are introduced and validated against conformational ensembles obtained from molecular dynamics simulations. This framework can explain a range of phenomena, such as the occurrence of an allosteric entropy change in the absence of any noticeable structural change. PMID- 26285737 TI - Polymer Multilayers that Promote the Rapid Release and Contact Transfer of DNA. AB - We report a layer-by-layer approach to the fabrication of thin polymer-based multilayers that release DNA rapidly in physiologically relevant environments. This approach exploits the properties of a weak anionic polyelectrolyte [poly(acrylic acid); PAA] to disrupt ionic interactions and promote disassembly in coatings that otherwise erode slowly. We investigated this approach using multilayers fabricated from plasmid DNA and linear poly(ethylenimine) (LPEI), a model synthetic cationic polymer used widely for DNA delivery. LPEI/DNA multilayers erode and release DNA slowly over ~4 days when incubated in PBS buffer. In contrast, substitution of every other layer of DNA with PAA lead to thin films that released DNA rapidly, with >60% being released in the first 5 min. These quick-release coatings release bioactive DNA and can be used to fabricate uniform coatings on a variety of objects, including the tips of inflatable balloon catheters. We demonstrate that these coatings can promote high levels of cell transfection in vitro and the robust contact transfer and expression of DNA in vascular tissue in vivo using a rat model of vascular injury. These materials provide useful alternatives to multilayers and other coatings that promote the prolonged release of DNA. More broadly, approaches that depart from the use of degradable polymers to promote film erosion create opportunities to design new gene delivery coatings using a broader range of polymer-based building blocks designed for other gene delivery applications. With further development, this approach could thus provide a new and useful platform for the rapid contact transfer of DNA to cells and tissues of interest in a range of fundamental and applied contexts. PMID- 26285738 TI - Normobaric Hyperoxia Preconditioning Induces Changes in the Brain Lipidome. AB - Recent investigations have demonstrated that normobaric hyperoxia induces neuroprotection against ischemic injury. The aim of study was to determine the survey of HO (hyperoxia) preconditioning on brain lipidome.The animals were assigned into three groups, the first experimental group was exposed to 95% inspired HO for 4 h /day for six consecutive days. The second experimental group considered as the control group and was exposed to 21% oxygen as room air (RA) in the same chamber. The third group acted as sham, which was under the stress of surgery condition without ischemia. The first two groups were divided into 2 subgroups, intact (without any surgery) and middle cerebral artery occlusion- operated (MCAO). Twenty-four hours after exposure to hyperoxia, MCAO subgroups were subjected to 60 min of right middle cerebral artery occlussion. After 24 h reperfusion, infarct volume (IV) and neurological deficit score (NDS) were assessed in MCAO subgroup. Brain lipidomics were measured in the intact subgroup. Preconditioning with HO significantly reduced NDS and IV and elevated the level of phosphatidylethanolamine (PE), sphingomyelin (SM), cholesterol ester (CE), cholesterol (Chol), phosphatidylcholine (PC), triglyceride (TG) and cerebroside (CB) in the brain as compared with the control (sham and RA). HO preconditioning, significantly decreased the brain ceramide (Cer) and lyso- phosphatidylcholine (Lyso-PC or LPC) levels. Preconditioning with HO decreases brain ischemia injury via changes in brain lipidomics and significantly decreases the brain ceramides (CER).Although more studies are required to explain the mechanisms of time course of neuroprotection, HO preconditioning partly decreases brain ischemia injury via changes in brain lipidome. PMID- 26285739 TI - Corrigendum for: Plastid casein kinase 2 knockout reduces abscisic acid (ABA) sensitivity, thermotolerance, and expression of ABA- and heat-stress-responsive nuclear genes. PMID- 26285740 TI - Importance of re-calibration time on pulse contour analysis agreement with thermodilution measurements of cardiac output: a retrospective analysis of intensive care unit patients. AB - We assessed the effect of re-calibration time on cardiac output estimation and trending performance in a retrospective analysis of an intensive care unit patient population using error grid analyses. Paired thermodilution and arterial blood pressure waveform measurements (N = 2141) from 222 patient records were extracted from the Multiparameter Intelligent Monitoring in Intensive Care II database. Pulse contour analysis was performed by implementing a previously reported algorithm at calibration times of 1, 2, 8 and 24 h. Cardiac output estimation agreement was assessed using Bland-Altman and error grid analyses. Trending was assessed by concordance and a 4-Quadrant error grid analysis. Error between pulse contour and thermodilution increased with longer calibration times. Limits of agreement were -1.85 to 1.66 L/min for 1 h maximum calibration time compared to -2.70 to 2.41 L/min for 24 h. Error grid analysis resulted in 74.2 % of points bounded by 20 % error limits of thermodilution measurements for 1 h calibration time compared to 65 % for 24 h. 4-Quadrant error grid analysis showed <75 % of changes in pulse contour estimates to be within +/-80 % of the change in the thermodilution measurement at any calibration time. Shorter calibration times improved the agreement of cardiac output pulse contour estimates with thermodilution. Use of minimally invasive pulse contour methods in intensive care monitoring could benefit from prospective studies evaluating calibration protocols. The applied pulse contour analysis method and thermodilution showed poor agreement to monitor changes in cardiac output. PMID- 26285742 TI - VEGF Splicing and the Role of VEGF Splice Variants: From Physiological Pathological Conditions to Specific Pre-mRNA Splicing. AB - During this past decade, the vascular endothelial growth factor (VEGF) pathway has been extensively studied. VEGF is a paradigm of molecular regulation since its expression is controlled at all possible steps including transcription, mRNA stability, translation, and pre-mRNA splicing. The latter form of molecular regulation is probably the least studied. This field has been neglected; yet different forms of VEGF with different sizes and different physiological properties issued from alternative splicing have been described a long time ago. Recently a new level of complexity was added to the field of splicing of VEGF pre mRNA. Whereas thousands of publications have described VEGF as a pro-angiogenic factor, an alternative splicing event generates specific anti-angiogenic forms of VEGF that only differ from the others by a modification in the last six amino acids of the protein. According to the scientists who discovered these isoforms, which are indistinguishable from the pro-angiogenic ones with pan VEGF antibodies, some of the literature on VEGF is at least inexact if not completely false. Moreover, the presence of anti-angiogenic forms of VEGF may explain the disappointing efficacy of anti-VEGF therapies on the overall survival of patients with different forms of cancers and with wet age-related macular degeneration. This review focuses on the existence of the different alternative splice variants of VEGF and the molecular mechanisms associated with their expression and function. PMID- 26285741 TI - Monitoring of cerebral blood flow autoregulation in adults undergoing sevoflurane anesthesia: a prospective cohort study of two age groups. AB - Autoregulation of blood flow is a key feature of the human cerebral vascular system to assure adequate oxygenation and metabolism of the brain under changing physiological conditions. The impact of advanced age and anesthesia on cerebral autoregulation remains unclear. The primary objective of this study was to determine the effect of sevoflurane anesthesia on cerebral autoregulation in two different age groups. This is a follow-up analysis of data acquired in a prospective observational cohort study. One hundred thirty-three patients aged 18 40 and >=65 years scheduled for major noncardiac surgery under general anesthesia were included. Cerebral autoregulation indices, limits, and ranges were compared in young and elderly patient groups. Forty-nine patients (37 %) aged 18-40 years and 84 patients (63 %) aged >=65 years were included in the study. Age-adjusted minimum alveolar concentrations of sevoflurane were 0.89 +/- 0.07 in young and 0.99 +/- 0.14 in older subjects (P < 0.001). Effective autoregulation was found in a blood pressure range of 13.8 +/- 9.8 mmHg in young and 10.2 +/- 8.6 mmHg in older patients (P = 0.079). The lower limit of autoregulation was 66 +/- 12 mmHg and 73 +/- 14 mmHg in young and older patients, respectively (P = 0.075). The association between sevoflurane concentrations and autoregulatory capacity was similar in both age groups. Our data suggests that the autoregulatory plateau is shortened in both young and older patients under sevoflurane anesthesia with approximately 1 MAC. Lower and upper limits of cerebral blood flow autoregulation, as well as the autoregulatory range, are not influenced by the age of anesthetized patients. Trial registration ClinicalTrials.gov (NCT00512200). PMID- 26285743 TI - Detection and Quantification of VEGF Isoforms by ELISA. AB - Vascular endothelial growth factor (VEGF) is a potent mitogen for endothelial cells and plays an important role in physiological and tumor angiogenesis. The human VEGF gene has eight exons. Different VEGF isoforms are expressed via alternative RNA splicing and VEGF121 and VEGF165 are the major isoforms present in human tissues. The exact roles of these different VEGF isoforms are not totally clear. Assays to detect specific VEGF isoforms in biological samples are needed to understand the biological functions of these different VEGF isoforms and to better assess their potential use as predicative biomarkers for anti angiogenic therapy. Because monoclonal antibodies specific to different VEGF isoforms are lacking, we used antibodies directed to different epitopes on VEGF165 in a set of three enzyme-linked immunosorbent assays (ELISAs) to assess the amount of VEGF121 and VEGF165 as well as VEGF110, which can be generated by plasmin cleavage in vivo. The first ELISA detects VEGF165. The second ELISA detects both VEGF121 and VEGF165. The third ELISA detects VEGF165, VEGF121, and VEGF110. The concentrations of VEGF121 can be assessed from the difference in VEGF concentrations measured by the second and the first ELISAs; the concentrations of VEGF110 can be assessed from the difference in VEGF concentrations measured by the third and the second ELISAs. The same assay strategy may be used to assess the amount of other VEGF isoforms if antibodies directed against the desired amino acids in those isoforms can be obtained. PMID- 26285744 TI - Quantitation of Circulating Neuropilin-1 in Human, Monkey, Mouse, and Rat Sera by ELISA. AB - Neuropilin-1 (NRP1) is a single spanning transmembrane glycoprotein that acts as a co-receptor for class 3 semaphorins and vascular endothelial growth factors. Naturally occurring soluble NRP1 isoforms containing partial extracellular domain (ECD) have been reported. In addition to soluble NRP1, full-length NRP1 ECD has also been identified in human and animal sera. Here, we describe primate and rodent NRP1 ELISAs that measure total circulating NRP1 including soluble NPR1 and NRP1 ECD in human, monkey, mouse, and rat sera. PMID- 26285745 TI - Detection and Quantification of Vascular Endothelial Growth Factor Receptor Tyrosine Kinases in Primary Human Endothelial Cells. AB - Proteins differ widely in their pattern of expression depending on organism, tissue, and regulation in response to changing conditions. In the mammalian vasculature, the endothelium responds to vascular endothelial growth factors (VEGFs) via membrane-bound receptor tyrosine kinases (VEGFRs) to modulate many aspects of vascular physiology including vasculogenesis, angiogenesis, and blood pressure. Studies on VEGFR biology are thus dependent on detecting expression levels in different cell types and evaluating how changes in protein levels correlate with changing conditions including circulating VEGF levels. Here, we present a robust immunoblot-based protocol for detecting and quantifying VEGFRs in human endothelial cells. Using internal and external standards, we can rapidly evaluate receptor copy number and assess how this is altered in response to the cellular environment. PMID- 26285746 TI - Induction of VEGF Secretion in Cardiomyocytes by Mechanical Stretch. AB - Cells respond to their environment by relaying mechanical force into biochemical stimuli that activate intracellular signal transduction pathways. Subjecting cells to in vitro mechanical stretch can mimic cellular responses to changes in the rigidity of the extracellular matrix. Here we describe an in vitro model system that mimics stretch overload in vivo. In this stretch-mediated hypertrophy model, adult rat cardiomyocytes attached to laminin-coated flexible membranes are subjected to cyclic mechanical stretch at an extension level of 10 % at 30 cycles/min. At various time points VEGF secretion into the media is collected and quantitated. PMID- 26285747 TI - Chromatin Immunoprecipitation Assay: Examining the Interaction of NFkB with the VEGF Promoter. AB - The chromatin immunoprecipitation (ChIP) assay is a versatile technique used to evaluate the association of proteins with specific DNA regions both in vivo and in vitro. This assay can be used to identify proteins associated with a specific region of the genome, or the opposite, to identify the many regions of the genome associated with a particular protein. The ChIP assay can also be used to analyze binding of transcription factors, transcription cofactors, DNA replication factors, and DNA repair proteins. Here we describe a useful ChIP-qPCR protocol to examine the interaction of NFkB with the VEGF promoter in adult rat primary cardiomyocytes that have been mechanically stretched after attaching to the extracellular matrix protein laminin. PMID- 26285748 TI - An Overview of VEGF-Mediated Signal Transduction. AB - Vascular endothelial growth factor (VEGF) plays a fundamental role in angiogenesis and endothelial cell biology, and has been the subject of intense study as a result. VEGF acts via a diverse and complex range of signaling pathways, with new targets constantly being discovered. This review attempts to summarize the current state of knowledge regarding VEGF cell signaling in endothelial and cardiovascular biology, with a particular emphasis on its role in angiogenesis. PMID- 26285749 TI - Identification of Receptor Tyrosine Kinase Inhibitors Using Cell Surface Biotinylation and Affinity Isolation. AB - The mammalian vascular endothelial growth factor receptor tyrosine kinases (VEGFRs) bind circulating growth factors and regulate the process of angiogenesis. The discovery of new small molecules that target the enzymatic activity of the VEGFR family as potential antiangiogenic drugs is of much commercial interest in the pharmaceutical sector. Here, we describe the use of a combined cell surface biotinylation and affinity isolation procedure to monitor ligand-stimulated VEGFR trafficking in endothelial cells, in which novel VEGFR inhibitors from chemical libraries can be identified by their ability to inhibit receptor internalization. Unlike a traditional cell-free enzyme activity assay, such a cell-based approach provides a physiologically relevant readout of inhibitor activity. In this example, we use the VEGF-A-VEGFR-2 axis and the well characterized tyrosine kinase inhibitor sunitinib as a working model; however this technique is highly applicable for the identification of inhibitors to other receptor tyrosine kinases. PMID- 26285750 TI - Analysis of VEGF-Mediated ERK5 Activity in Endothelial Cells. AB - Extracellular signal-regulated kinase 5 (ERK5), also known as big MAPK (BMK1), is the most recently identified member of the mitogen-activated kinase pathway. It is ubiquitously expressed in mammalian cells and is activated by a number of growth factors. Gene knockout studies in mice have shown a critical role for ERK5 cardiovascular development and vascular integrity. Current methods to detect ERK5 activation in cells have relied on in vitro kinase assays and more recently phospho-specific antibodies. However, antibodies produced against phosphorylated proteins can often yield inconsistent data. Phos-tagTM Acrylamide is a reagent that enables specific tagging of phosphorylated proteins, resulting in retarded mobility and a distinct upward band shift from the non-phosphorylated protein following SDS-PAGE. Here, we describe the details of Phosphate affinity SDS-PAGE of ERK5 using acrylamide-pendant Phos-tagTM. PMID- 26285751 TI - In Vitro Angiogenesis Assays. AB - Angiogenesis is a key process mediated by VEGF, and the study of angiogenic mechanisms has clinical importance in a variety of pathological conditions, including ischemic heart disease and cancer. In vitro angiogenesis assays are based on the innate ability of endothelial cells to migrate and form tube like structures in response to VEGF stimulation. Although they are arguably not as physiologically relevant as in vivo angiogenesis models they still represent a relatively quick and useful method for looking at VEGF function. There are several different methods for studying in vitro angiogenesis and these are detailed here along with protocols for image capture and analysis. PMID- 26285752 TI - Chemotactic Migration of Endothelial Cells Towards VEGF-A165. AB - In vitro assays of endothelial cell migration have led to critical insights into the mechanisms of angiogenesis. The transwell assay, or modified Boyden chamber assay was developed to investigate chemotaxis, which corresponds to the directional migration of cells in response to a chemoattractant gradient. It is a robust and easy-to-use assay that does not require expensive equipment. In the modified Boyden chamber assay, two compartments are separated with a porous membrane through which cells can migrate. The lower compartment contains the chemoattractant, creating a gradient by diffusing into the upper chamber containing the cells. The cells will migrate through the membrane and remain on the lower side of the membrane, where they can finally be fixed and counted. PMID- 26285753 TI - Vasculogenesis and Angiogenesis in VEGF Receptor-1 Deficient Mice. AB - Vascular endothelial growth factor receptor-1 (VEGFR-1)/Flt-1 is a transmembrane tyrosine kinase receptor for VEGF-A, VEGF-B, and placental growth factor (PlGF). VEGFR-1 is an enigmatic molecule whose precise role in postnatal angiogenesis remains controversial. Although many postnatal and adult studies have been performed by manipulating VEGFR-1 ligands, including competitive binding by truncated VEGFR-1 protein, neutralization by antibodies, or specific ligand overexpression or knockout, much less is known at the level of the receptor per se, especially in vivo. Perplexingly, while VEGFR-1 negatively regulates endothelial cell differentiation during development, it has been implied in promoting angiogenesis under certain conditions in adult tissues, especially in tumors and ischemic tissues. Additionally, it is unclear how VEGFR-1 is involved in vascular maturation and maintenance of vascular quiescence in adult tissues. To facilitate further investigation, we generated a conditional knockout mouse line for VEGFR-1 and characterized angiogenesis in postnatal and adult mice, including angiogenesis in ischemic myocardium. These methods are briefly outlined in this chapter. We also discuss these findings in the context of the interplay between VEGF family members and their receptors, and summarize various mouse models in the VEGF pathway. PMID- 26285754 TI - The Embryonic Mouse Hindbrain and Postnatal Retina as In Vivo Models to Study Angiogenesis. AB - Angiogenesis, the growth of new blood vessels from preexisting ones, is a fundamental process for organ development, exercise-induced muscle growth, and wound healing, but is also associated with different diseases such as cancer and neovascular eye disease. Accordingly, elucidating the molecular and cellular mechanisms of angiogenesis has the potential to identify new therapeutic targets to stimulate new vessel formation in ischemic tissues or inhibit pathological vessel growth in disease. This chapter describes the mouse embryo hindbrain and postnatal retina as models to study physiological angiogenesis and provides detailed protocols for tissue dissection, sample staining, and analysis. PMID- 26285755 TI - VEGF Gene Transfer to the Utero-Placental Circulation of Pregnant Guinea Pigs to Enhance Fetal Growth. AB - In this chapter, we describe a novel method of adenoviral gene transfer to the uterine and radial arteries of pregnant guinea pigs to improve fetal growth. Adenoviruses encoding VEGF-A165 or a reporter gene beta-galactosidase were reconstituted in pluronic gel and applied topically to the exposed uterine and radial arteries following laparotomy. Pluronic gel is a thermosensitive gel that is liquid at 4 degrees C, but becomes solid as soon as it comes in contact with body temperature. It thereby acts as a slow-release vehicle for viral vectors to the target tissue and also facilitates closer contact of the viruses with the host tissue. Our studies have shown that adenoviral gene delivery using pluronic gel resulted in the highest transduction efficiency compared to intra-arterial administration or external administration in PBS as a vehicle, when measured by X gal staining, immunohistochemistry, or Western blotting. PMID- 26285756 TI - VEGF Gene Transfer to the Utero-Placental Circulation of Pregnant Sheep to Enhance Fetal Growth. AB - In this chapter, we describe a safe and effective approach to achieve local VEGF gene transfer to the uterine arteries in pregnant sheep using direct injection of viral vectors into the uterine arteries. This approach resulted in improved fetal growth in growth-restricted pregnancies. Adenoviral vectors encoding VEGF-A165 or a reporter gene beta-galactosidase were dissolved in 10 mL normal saline shortly before administration. A midline laparotomy was performed and the course of the uterine artery identified. The main trunk (just prior to the first bifurcation) was mobilized by dissection and a vessel loop placed beneath it in order to elevate the artery, which was then occluded digitally just proximal to the planned injection site. The adenoviral solution was slowly injected over 1 min, and the occlusion was maintained for a further 4 min to maximize transduction of the downstream endothelium. After ensuring hemostasis, the abdomen was closed in layers. PMID- 26285757 TI - Generation of Targeted Mutations in Zebrafish Using the CRISPR/Cas System. AB - Several strategies have been developed to generate targeted gene disruptions in zebrafish.Here we developed a simple targeted gene inactivation strategy in zebrafish using a clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas) system. By injecting two simple in vitro synthesized components [Cas9 mRNA and single guide (sgRNA)] into one-cell-stage embryos, mutations of the target gene could be efficiently generated. We used a codon-optimized version of Cas9 to improve its translation efficiency in zebrafish. In addition, we designed a cloning-free strategy to facilitate the synthesis of sgRNA. The system allows biallelic inactivation of multiple genes simultaneously by co-injecting a mix of sgRNAs with a single Cas9 construct. This flexible strategy of gene inactivation provides an efficient way to interrogate gene functions and genetic interactions in zebrafish. PMID- 26285758 TI - Recombinant Expression of Trichoderma reesei Cel61A in Pichia pastoris: Optimizing Yield and N-terminal Processing. AB - The auxiliary activity family 9 (AA9, formerly GH61) harbors a recently discovered group of oxidative enzymes that boost cellulose degradation. Indeed, these lytic polysaccharide monooxygenases (LPMOs) are able to disrupt the crystalline structure of cellulose, thereby facilitating the work of hydrolytic enzymes involved in biomass degradation. Since these enzymes require an N terminal histidine residue for activity, their recombinant production as secreted protein is not straightforward. We here report the expression optimization of Trichoderma reesei Cel61A (TrCel61A) in the host Pichia pastoris. The use of the native TrCel61A secretion signal instead of the alpha-mating factor from Saccharomyces cerevisiae was found to be crucial, not only to obtain high protein yields (>400 mg/L during fermentation) but also to enable the correct processing of the N-terminus. Furthermore, the LPMO activity of the enzyme is demonstrated here for the first time, based on its degradation profile of a cellulosic substrate. PMID- 26285760 TI - Comment to Vertical by Giordano CNSY-D-14-00096. PMID- 26285759 TI - Genetics of Type 2 Diabetes in African Americans. AB - Type 2 diabetes (T2D) is a global health problem showing substantial ethnic disparity in disease prevalence. African Americans have one of the highest prevalence of T2D in the USA but little is known about their genetic risks. This review summarizes the findings of genetic regions and loci associated with T2D and related glycemic traits using linkage, admixture, and association approaches in populations of African ancestry. In particular, findings from genome-wide association and exome chip studies suggest the presence of both ancestry-specific and shared loci for T2D and glycemic traits. Among the European-identified loci that are transferable to individuals of African ancestry, allelic heterogeneity as well as differential linkage disequilibrium and risk allele frequencies pose challenges and opportunities for fine mapping and identification of causal variant(s) by trans-ancestry meta-analysis. More genetic research is needed in African ancestry populations including the next-generation sequencing to improve the understanding of genetic architecture of T2D. PMID- 26285761 TI - Reference values for cerebral blood flow velocities in critically ill, sedated children. AB - OBJECTIVE: Transcranial Doppler ultrasound (TCD) is increasingly being used in the pediatric intensive care unit to assess cerebral hemodynamics during critical illness. However, no normative data in this patient population have been published to date. Therefore, we aimed to describe the anterior and posterior cerebral blood flow velocities in critically ill children undergoing mechanical ventilation and sedation. DESIGN: A prospective, observational cohort study was performed. Children with known or suspected acute or chronic neurologic conditions were excluded. Participants underwent TCD measurement of middle cerebral and basilar artery flow velocities. RESULTS: One hundred and forty children newborn to 17 years of age were enrolled. Measured values were lower in this cohort of children than the previously published cerebral flow velocities of normal, healthy children. CONCLUSIONS: Cerebral blood flow velocities of the basal cerebral arteries in critically ill, mechanically ventilated, sedated children are lower than in healthy children of the same age and gender published in previous studies. As such, the cerebral blood flow velocity (CBFV) values reported here may serve as a more accurate reference point when using TCD as a clinical tool to diagnose CBFV abnormalities and guide therapy in this patient population. PMID- 26285762 TI - Bilateral encephaloduroarteriosynangiosis (EDAS) in a 6-year-old female for moyamoya disease: case report and technical note with 12-year follow-up. AB - PURPOSE: To demonstrate that despite disease progression, indirect cerebral revascularisation via EDAS for moyamoya disease is able to maintain sufficient collateral blood supply over a 12-year period. METHODS: Case report of an individual patient with surgically managed moyamoya disease followed up with imaging and outpatient clinic assessments. RESULTS: Follow-up imaging and assessment over 12 years concluded with a good functional and radiographic outcome. CONCLUSION: The extensive follow-up in our case of a 6-year-old female treated with bilateral EDAS procedures for moyamoya disease demonstrates that despite disease progression over 12 years, sufficient collateral blood supply was maintained to achieve a good functional outcome. PMID- 26285763 TI - Severe liver and renal injuries following cerebral angiography: late life threatening complications of non-ionic contrast medium administration. AB - INTRODUCTION: Contrast-induced nephropathy requiring dialysis support is rarely reported, whereas severe liver injury after contrast agent administration has not been described in children yet. CLINICAL CASE: A previously healthy 10-year-old boy with diagnosis of cerebral arteriovenous malformation underwent a cerebral angiogram study with iohexol (3 mL/kg). After 4 days, he developed vomiting and abdominal pain. Laboratory results showed abnormal liver function tests, including marked elevation of transaminases. In the next day, he evolved with oliguria and blood arterial hypertension. At this time, he presented with worsening renal function tests. Peritoneal dialysis was required for 13 days. The patient had a self-limiting course and received only supportive treatment. CLINICAL PRESENTATION: This report highlights delayed complications related to low non-ionic contrast media with a rare presentation that can be neglected or unrecognized by pediatric specialties. PMID- 26285764 TI - High-Throughput Cytochrome P450 Cocktail Inhibition Assay for Assessing Drug-Drug and Drug-Botanical Interactions. AB - Detection of drug-drug interactions is essential during the early stages of drug discovery and development, and the understanding of drug-botanical interactions is important for the safe use of botanical dietary supplements. Among the different forms of drug interactions that are known, inhibition of cytochrome P450 (P450) enzymes is the most common cause of drug-drug or drug-botanical interactions. Therefore, a rapid and comprehensive mass spectrometry-based in vitro high-throughput P450 cocktail inhibition assay was developed that uses 10 substrates simultaneously against nine CYP isoforms. Including probe substrates for CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and two probes targeting different binding sites of CYP3A4/5, this cocktail simultaneously assesses at least as many P450 enzymes as previous assays while remaining among the fastest due to short incubation times and rapid analysis using ultrahigh pressure liquid chromatography-tandem mass spectrometry. The method was validated using known inhibitors of each P450 enzyme and then shown to be useful not only for single-compound testing but also for the evaluation of potential drug-botanical interactions using the botanical dietary supplement licorice (Glycyrrhiza glabra) as an example. PMID- 26285765 TI - Potent and Selective Inhibition of Plasma Membrane Monoamine Transporter by HIV Protease Inhibitors. AB - Plasma membrane monoamine transporter (PMAT) is a major uptake-2 monoamine transporter that shares extensive substrate and inhibitor overlap with organic cation transporters 1-3 (OCT1-3). Currently, there are no PMAT-specific inhibitors available that can be used in in vitro and in vivo studies to differentiate between PMAT and OCT activities. In this study, we showed that IDT307 (4-(4-(dimethylamino)phenyl)-1-methylpyridinium iodide), a fluorescent analog of 1-methyl-4-phenylpyridinium (MPP+), is a transportable substrate for PMAT and that IDT307-based fluorescence assay can be used to rapidly identify and characterize PMAT inhibitors. Using the fluorescent substrate-based assays, we analyzed the interactions of eight human immunodeficiency virus (HIV) protease inhibitors (PIs) with human PMAT and OCT1-3 in human embryonic kidney 293 (HEK293) cells stably transfected with individual transporters. Our data revealed that PMAT and OCTs exhibit distinct sensitivity and inhibition patterns toward HIV PIs. PMAT is most sensitive to PI inhibition whereas OCT2 and OCT3 are resistant. OCT1 showed an intermediate sensitivity and a distinct inhibition profile from PMAT. Importantly, lopinavir is a potent PMAT inhibitor and exhibited >120 fold selectivity toward PMAT (IC50 = 1.4 +/- 0.2 uM) over OCT1 (IC50 = 174 +/- 40 uM). Lopinavir has no inhibitory effect on OCT2 or OCT3 at maximal tested concentrations. Lopinavir also exhibited no or much weaker interactions with uptake-1 monoamine transporters. Together, our results reveal that PMAT and OCTs have distinct specificity exemplified by their differential interaction with HIV PIs. Further, we demonstrate that lopinavir can be used as a selective PMAT inhibitor to differentiate PMAT-mediated monoamine and organic cation transport from those mediated by OCT1-3. PMID- 26285766 TI - Phase I study of iniparib concurrent with monthly or continuous temozolomide dosing schedules in patients with newly diagnosed malignant gliomas. AB - Iniparib is a prodrug that converts to highly reactive cytotoxic metabolites intracellularly with activity in preclinical glioma models. We investigated the maximum tolerated dose (MTD) of iniparib with monthly (m) and continuous (c) temozolomide (TMZ) dosing schedules in patients with malignant gliomas (MG). Adults with newly diagnosed MG who had successfully completed >=80% of radiation (RT) and TMZ without toxicity received mTMZ dosing (150-200 mg/m(2) days 1-5/28 days) or cTMZ dosing (75 mg/m(2)/days * 6 weeks) in conjunction with iniparib (i.v. 2 days/week) in the adjuvant setting. Iniparib was dose escalated using a modified continual reassessment method (mCRM). 43 patients (32 male; 34 GBM, 8 AA, 1 gliosarcoma; median age 54 years; median KPS 90) were enrolled across 4 dose levels. In the mTMZ group, 2/4 patients had dose limiting toxicities (DLT) at 19 mg/kg/week (rash/hypersensitivity). At 17.2 mg/kg/week, 1/9 patients had a DLT (grade 3 fatigue). Additional grade 3 toxicities were neutropenia, lymphopenia, and nausea. In the cTMZ group, one DLT (thromboembolic event) occurred at 10.2 mg/kg/week. Dose escalation stopped at 16 mg/kg/week based on mCRM. The mean maximum plasma concentration of iniparib increased with dose. Concentration of the two major circulating metabolites, 4-iodo-3-aminobenzamide and 4-iodo-3-aminobenzoic acid, was <=5% of the corresponding iniparib concentration. Iniparib is well tolerated, at doses higher than previously investigated, in combination with TMZ after completion of RT + TMZ in patients with MG. Recommended phase 2 dosing of iniparib based on mCRM is 17.2 mg/kg/week with mTMZ and 16 mg/kg/week with cTMZ. An efficacy study of TMZ/RT + iniparib followed by TMZ + iniparib in newly diagnosed GBM using these doses has completed enrollment. Survival assessment is ongoing. PMID- 26285767 TI - Changes in functional MRI signals after 3D based radiotherapy of glioblastoma multiforme. AB - The purpose of our study was to examine the potential effects of conventional 3D based radiotherapy on functional MRI activation areas following the treatment of glioblastoma multiforme. Seventeen patients with a histologically proven glioblastoma multiforme were enrolled in this study. A functional MRI examination was performed alongside the planning CT and conventional MRI prior to the delivery of conventional 3D based radiotherapy. All patients received 3D based postoperative radiotherapy (up to 60 Gy) combined with temozolomide. Follow-up fMRI examinations were performed after completion of the treatment in the 6th week and in 3 months time. Changes of the task related activation areas were registered and analyzed. The difference in changes of high dose and low dose areas of the brain were also registered and analyzed. The comparison of the pretreatment and 6th week control fMRI activation areas revealed significant changes in motor activation and listening tasks in the case of brain areas which received a high dose (over 40 Gy). Based on the population level statistical parametric images (motor activation tasks) acquired at the 6th week control examination, a significant increase of signal was registered in the precuneus region and in the globus pallidus region. When comparing the 6th week and 3rd month activation signals, no significant changes were registered. Our results demonstrate the influence of radiotherapy on functional MRI signals within the human brain. Based on our findings, functional activation transfers from high dose areas to low dose areas. In case of the motor activation tasks, activations of the secondary motor area were observed following radiotherapy. PMID- 26285768 TI - A phase II trial of tamoxifen and bortezomib in patients with recurrent malignant gliomas. AB - NF-kB inhibition by bortezomib enhances tamoxifen-induced apoptosis in preclinical glioma models. We conducted a single institution, phase II trial to evaluate efficacy and safety of high dose tamoxifen with bortezomib in adults with recurrent malignant gliomas. The primary endpoint was radiographic response. Concurrent enzyme inducing anticonvulsants and grade >=2 peripheral neuropathy were exclusion criteria. Patients received tamoxifen (120 mg PO twice daily) and bortezomib (1.3 mg/m2 IV on days 3, 6, 10, 13, 24, 27, 31, and 34) per 6-week cycles. We enrolled 42 patients with anaplastic gliomas (AGs, n = 12) and glioblastomas (GBMs, n = 30), 32 males and 10 females. Median age was 38 years (range 22-65) and 48 years (range 19-68) for AGs and GBMs, respectively. median karnofsky performance status was 90% (range 70-100) for AGs and 80% (range 60 100) for GBMs. Median prior therapies was 3, ranging 1-7. Grade >=3 toxicities included lymphopenia (4/42), hypophosphatemia (3/42), thromobocytopenia (2/42), and 1/42 with hyponatremia, headache, dyspnea, or DVT. One patient withdrew consent, two were removed for toxicity, and all others discontinued for progression. Among 40 patients evaluable for response, only one achieved stable disease for 3 months; all others progressed rapidly. For AGs and GBMs respectively, median progression-free survival was 5.9 and 5.7 weeks and median overall survival was 25.6 and 14.7 weeks. The study was closed due to poor accrual and therapeutic futility. Combination tamoxifen and bortezomib has no activity in recurrent malignant gliomas. Poor penetration across blood brain barrier of bortezomib likely limited efficacy. PMID- 26285769 TI - Simulated bone remodeling around tilted dental implants in the anterior maxilla. AB - Dental implants have to be placed with the long axis in different angulations due to the change in bone morphology. The objective of this study was to investigate the different bone remodeling response induced by the tilted dental implants and to assess whether it could lead to bone loss and implant failure. In this study, bone remodeling due to palato-labially inclined dental implants placed in the anterior maxillary incisor region was simulated. CT-based finite element models of a maxillary bone with dental implants were created herein. Five dental implants were placed at [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text], respectively. The remodeling progression was recorded and compared. Model [Formula: see text] (palatal side) shows the highest bone density values, but the inclined implant at [Formula: see text] (labial side) leads to significant bone loss. From a biomechanical perspective, it is speculated that a palatally inclined implant is more likely to enhance the bone density in the maxillary anterior region, but labial inclination of implant could jeopardize its stability. PMID- 26285770 TI - Sudden cardiac arrest in sports - need for uniform registration: A Position Paper from the Sport Cardiology Section of the European Association for Cardiovascular Prevention and Rehabilitation. AB - There are large variations in the incidence, registration methods and reported causes of sudden cardiac arrest/sudden cardiac death (SCA/SCD) in competitive and recreational athletes. A crucial question is to which degree these variations are genuine or partly due to methodological incongruities. This paper discusses the uncertainties about available data and provides comprehensive suggestions for standard definitions and a guide for uniform registration parameters of SCA/SCD. The parameters include a definition of what constitutes an 'athlete', incidence calculations, enrolment of cases, the importance of gender, ethnicity and age of the athlete, as well as the type and level of sporting activity. A precise instruction for autopsy practice in the case of a SCD of athletes is given, including the role of molecular samples and evaluation of possible doping. Rational decisions about cardiac preparticipation screening and cardiac safety at sport facilities requires increased data quality concerning incidence, aetiology and management of SCA/SCD in sports. Uniform standard registration of SCA/SCD in athletes and leisure sportsmen would be a first step towards this goal. PMID- 26285771 TI - Impact of training methods and patient characteristics on exercise capacity in patients in cardiovascular rehabilitation. AB - AIM: We aimed to identify patient characteristics and comorbidities that correlate with the initial exercise capacity of cardiac rehabilitation (CR) patients and to study the significance of patient characteristics, comorbidities and training methods for training achievements and final fitness of CR patients. METHODS: We studied 557 consecutive patients (51.7 +/- 6.9 years; 87.9% men) admitted to a three-week in-patient CR. Cardiopulmonary exercise testing (CPX) was performed at discharge. Exercise capacity (watts) at entry, gain in training volume and final physical fitness (assessed by peak O2 utilization (VO2peak) were analysed using analysis of covariance (ANCOVA) models. RESULTS: Mean training intensity was 90.7 +/- 9.7% of maximum heart rate (81% continuous/19% interval training, 64% additional strength training). A total of 12.2 +/- 2.6 bicycle exercise training sessions were performed. Increase of training volume by an average of more than 100% was achieved (difference end/beginning of CR: 784 +/- 623 watts * min). In the multivariate model the gain in training volume was significantly associated with smoking, age and exercise capacity at entry of CR. The physical fitness level achieved at discharge from CR as assessed by VO2peak was mainly dependent on age, but also on various factors related to training, namely exercise capacity at entry, increase of training volume and training method. CONCLUSION: CR patients were trained in line with current guidelines with moderate-to-high intensity and reached a considerable increase of their training volume. The physical fitness level achieved at discharge from CR depended on various factors associated with training, which supports the recommendation that CR should be offered to all cardiac patients. PMID- 26285772 TI - Liposomal Nanoparticles of a Spleen Tyrosine Kinase P-Site Inhibitor Amplify the Potency of Low Dose Total Body Irradiation Against Aggressive B-Precursor Leukemia and Yield Superior Survival Outcomes in Mice. AB - This study was designed to improve the efficacy of radiation therapy against radiation-resistant leukemia. We report that the potency of low dose radiation therapy against B-precursor acute lymphoblastic leukemia (BPL) can be markedly enhanced by combining radiation with a liposomal nanoparticle (LNP) formulation of the SYK-P-site inhibitor C61 ("C61-LNP"). C61-LNP plus low dose total body irradiation (TBI) was substantially more effective than TBI alone or C61-LNP alone in improving the event-free survival outcome NOD/SCID mice challenged with an otherwise invariably fatal dose of human ALL xenograft cells derived from relapsed BPL patients. C61-LNP plus low dose TBI also yielded progression-free survival, tumor-free survival and overall survival outcomes in CD22DeltaE12 * BCR ABL double transgenic mice with advanced stage, radiation-resistant BPL with lymphomatous features that were significantly superior to those of mice treated with TBI alone or C61-LNP alone. PMID- 26285773 TI - Use of a risk quiz to predict infection for sexually transmitted infections: a retrospective analysis of acceptability and positivity. AB - BACKGROUND: Individuals who are sexually active may want to make a decision as to whether they are at risk for having a sexually transmitted infection (STI) such as Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis. Our goal was to develop and evaluate a simple self-taken sexual risk quiz for participants, ordering an online STI self-collection test kit to determine whether the score predicted infection status. METHODS: As part of the IWantTheKit programme for home sample self-collection for STIs, 2010-2013, the programme asked male and female users to voluntarily take a risk quiz. The six-question quiz was about risk behaviour and included an age question. Data analyses were stratified by gender as determined a priori. Scores 0-10 were stratified into risk groups for each gender based on similar risk score-specific STI prevalence. Retrospective analyses were performed to assess whether risk group predicted aggregate STI positivity. Urogenital/rectal mailed samples were tested by nucleic acid amplification tests. RESULTS: More females (N=836) than males (N=558) provided voluntary risk scores. The percentage of eligible participants who submitted scores was 43.9% for both females and males. There was a higher STI infection rate in females (14.0%) than in males (7.0%) for having any STI (p<0.001). Multivariate logistic analysis for females, which controlled for age and race, demonstrated that a higher risk score group independently predicted risk for having an STI (OR of 2.2 for risk scores 5-7 and 4.2 OR for scores of 8 10). For males, the multivariate model, which controlled for race, indicated that no risk score group was associated having an STI. CONCLUSIONS: Results of a participant's own sexual risk quiz score independently predicted STI positivity for women, but not for men. Further study of this simple risk quiz is required. PMID- 26285775 TI - The ABC of diabetes: Are we doing enough? PMID- 26285774 TI - Comparative gene-expression profiling of CD133(+) and CD133(-) D10 melanoma cells. AB - AIMS: The present study aimed to compare the gene-expression profiling of CD133(+) and CD133(-) D10 cells. MATERIALS & METHODS: Cancer stem cell-like properties and gene-expression profiling of CD133(+) D10 cells versus CD133(-) cells were evaluated. RESULTS: The CD133(+) D10 cells showed significantly higher clonogenic and spheroid forming potential, also higher expression of stemness genes NANOG and OCT4A compared with the CD133(-) cells. Gene-expression profiling of CD133(+) versus CD133(-) D10 cells revealed that 130 genes including ABC transporter superfamily (ABCC1, ABCG2 and ABCC6) were upregulated, while 61 genes including apoptosis modifying genes (CASP8 and TNFRSF4) were downregulated. CONCLUSION: We conclude that many genes involved in drug resistance and tumor aggressiveness are upregulated in CD133(+) D10 cells and targeting them might be an efficient strategy for treatment of melanoma. PMID- 26285776 TI - More Trees, More Poverty? The Socioeconomic Effects of Tree Plantations in Chile, 2001-2011. AB - Tree plantations play a controversial role in many nations' efforts to balance goals for economic development, ecological conservation, and social justice. This paper seeks to contribute to this debate by analyzing the socioeconomic impact of such plantations. We focus our study on Chile, a country that has experienced extraordinary growth of industrial tree plantations. Our analysis draws on a unique dataset with longitudinal observations collected in 180 municipal territories during 2001-2011. Employing panel data regression techniques, we find that growth in plantation area is associated with higher than average rates of poverty during this period. PMID- 26285777 TI - Would you test for 5000 Shillings? HIV risk and willingness to accept HIV testing in Tanzania. AB - OBJECTIVES: Despite substantial public health efforts to increase HIV testing, testing rates have plateaued in many countries and rates of repeat testing for those with ongoing risk are low. To inform policies aimed at increasing uptake of HIV testing, we identified characteristics associated with individuals' willingness-to-accept (WTA) an HIV test in a general population sample and among two high-risk populations in Moshi, Tanzania. METHODS: In total, 721 individuals, including randomly selected community members (N = 402), female barworkers (N = 135), and male Kilimanjaro mountain porters (N = 184), were asked in a double bounded contingent valuation format if they would test for HIV in exchange for 2000, 5000 or 10,000 Shillings (approximately $1.30, $3.20, and $6.40, respectively). The study was conducted between September 2012 and February 2013. RESULTS: More than one quarter of participants (196; 27 %) stated they would be willing to test for Tanzania Shilling (TSH) 2000, whereas one in seven (98; 13.6 %) required more than TSH 10,000. The average WTA estimate was TSH 4564 (95 % Confidence Interval: TSH 4201 to 4927). Significant variation in WTA estimates by gender, HIV risk factors and other characteristics plausibly reflects variation in individuals' valuations of benefits of and barriers to testing. WTA estimates were higher among males than females. Among males, WTA was nearly one-third lower for those who reported symptoms of HIV than those who did not. Among females, WTA estimates varied with respondents' education, own and partners' HIV testing history, and lifetime reports of transactional sex. For both genders, the most significant association was observed with respondents' perception of the accuracy of the HIV test; those believing HIV tests to be completely accurate were willing to test for approximately one third less than their counterparts. The mean WTA estimates identified in this study suggest that within the study population, incentivized universal HIV testing could potentially identify undiagnosed HIV infections at an incentive cost of $150 per prevalent infection and $1400 per incident infection, with corresponding costs per quality adjusted life year (QALY) gained of $70 for prevalent and $620 for incident HIV infections. CONCLUSIONS: The results support the value of information about the accuracy of HIV testing, and suggest that relatively modest amounts of money may be sufficient to incentivize at-risk populations to test. PMID- 26285779 TI - Microscopy image analysis of p63 immunohistochemically stained laryngeal cancer lesions for predicting patient 5-year survival. AB - The aim of the present study was to design a microscopy image analysis (MIA) system for predicting the 5-year survival of patients with laryngeal squamous cell carcinoma, employing histopathology images of lesions, which had been immunohistochemically (IHC) stained for p63 expression. Biopsy materials from 42 patients, with verified laryngeal cancer and follow-up, were selected from the archives of the University Hospital of Patras, Greece. Twenty six patients had survived more than 5 years and 16 less than 5 years after the first diagnosis. Histopathology images were IHC stained for p63 expression. Images were first processed by a segmentation method for isolating the p63-expressed nuclei. Seventy-seven features were evaluated regarding texture, shape, and physical topology of nuclei, p63 staining, and patient-specific data. Those features, the probabilistic neural network classifier, the leave-one-out (LOO), and the bootstrap cross-validation methods, were used to design the MIA-system for assessing the 5-year survival of patients with laryngeal cancer. MIA-system accuracy was about 90 % and 85 %, employing the LOO and the Bootstrap methods, respectively. The image texture of p63-expressed nuclei appeared coarser and contained more edges in the 5-year non-survivor group. These differences were at a statistically significant level (p < 0.05). In conclusion, this study has proposed an MIA-system that may be of assistance to physicians, as a second opinion tool in assessing the 5-year survival of patients with laryngeal cancer, and it has revealed useful information regarding differences in nuclei texture between 5-year survivors and non-survivors. PMID- 26285778 TI - Altiratinib Inhibits Tumor Growth, Invasion, Angiogenesis, and Microenvironment Mediated Drug Resistance via Balanced Inhibition of MET, TIE2, and VEGFR2. AB - Altiratinib (DCC-2701) was designed based on the rationale of engineering a single therapeutic agent able to address multiple hallmarks of cancer (1). Specifically, altiratinib inhibits not only mechanisms of tumor initiation and progression, but also drug resistance mechanisms in the tumor and microenvironment through balanced inhibition of MET, TIE2 (TEK), and VEGFR2 (KDR) kinases. This profile was achieved by optimizing binding into the switch control pocket of all three kinases, inducing type II inactive conformations. Altiratinib durably inhibits MET, both wild-type and mutated forms, in vitro and in vivo. Through its balanced inhibitory potency versus MET, TIE2, and VEGFR2, altiratinib provides an agent that inhibits three major evasive (re)vascularization and resistance pathways (HGF, ANG, and VEGF) and blocks tumor invasion and metastasis. Altiratinib exhibits properties amenable to oral administration and exhibits substantial blood-brain barrier penetration, an attribute of significance for eventual treatment of brain cancers and brain metastases. PMID- 26285780 TI - Two-stage autotransplantation of human submandibular gland: a novel approach to treat postradiogenic xerostomia. AB - Xerostomia is a persistent side effect of radiotherapy (RT), which severely reduces the quality of life of the patients affected. Besides drug treatment and new irradiation strategies, surgical procedures aim for tissue protection of the submandibular gland. Using a new surgical approach, the submandibular gland was autotransplanted in 6 patients to the patient's forearm for the period of RT and reimplanted into the floor of the mouth 2-3 months after completion of RT. Saxon's test was performed during different time points to evaluate patient's saliva production. Furthermore patients had to answer EORTC QLQ-HN35 questionnaire and visual analog scale. Following this two-stage autotransplantation, xerostomia in the patients was markedly reduced due to improved saliva production of the reimplanted gland. Whether this promising novel approach is a reliable treatment option for RT patients in general should be evaluated in further studies. PMID- 26285781 TI - A novel predictive marker for the recurrence of nasal polyposis following endoscopic sinus surgery. AB - We aimed to determine the value of neutrophil-to-lymphocyte (NLR) ratio for prediction of recurrence in patients subjected to endoscopic sinus surgery. Higher neutrophil counts mean more chronic inflammation so the NLR value could show the inflammatory level resulting with higher incidence of recurrence. From January 2011 to March 2013, we performed a retrospective review of the complete blood count samples from 192 patients with chronic sinusitis who underwent endoscopic sinus surgery. The patients were divided into two groups based on the presence of nasal polyps. NLR and platelet-to-lymphocyte (PLR) ratios were analyzed. Receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off value for significant differences in variables between the recurrence and non-recurrence groups. The ROC analysis results revealed an NLR cut-off of 3.13 and a PLR cut-off of 208.75. Our analysis revealed that NLR is an independent risk factor for recurrence of chronic sinusitis in patients subjected to endoscopic sinus surgery (p = 0.006), whereas the PLR was not a predictive factor for recurrence (p = 0.167). Our study revealed that the NLR could be used to predict disease recurrence before endoscopic sinus surgery. However, additional studies are needed to confirm these results. PMID- 26285782 TI - Formal intergenerational mentoring at Australian Men's Sheds: a targeted survey about mentees, mentors, programmes and quality. AB - Intergenerational mentoring enables a purposeful exchange of skills and knowledge to enhance individual and social outcomes for sub-groups at risk of health and social disparities. Male intergenerational mentoring may be an approach to help address these disparities in young men. Over 1000 Men's Sheds operate in Australia with 39% providing some form of mentoring mainly to youth. Yet, little is known about the variables intrinsic to creating and running quality programmes. This study aimed to identify the characteristics of formal intergenerational mentoring programmes, review their quality against the Australian Youth Mentoring Network (AYMN) quality benchmarks, and identify the factors that predict quality in these programmes. All known Australian Men's Sheds were invited to participate in an online cross-sectional survey. Forty sheds with formal mentor programmes completed the survey for a total of 387 mentees (mean = 9.7 mentees/programme), the majority being male. The majority of mentor programme facilitators were unpaid male volunteers aged 61 years and older, and programmes were unfunded. Promoting social and emotional well-being of the mentees was the primary focus in more than half of the programmes, and working on a shared construction project was the most common activity. Respondents rated the three most important factors that influenced programme effectiveness as being: (i) meaningful activities; (ii) mentors' approach; and (iii) a safe environment. Univariate analyses revealed that mentoring programmes that had a system in place for screening mentors, trained mentors and evaluated the programme were most likely to rate highly against the AYMN quality benchmarks. PMID- 26285783 TI - Decoding the Chemical Language of Motile Bacteria by Using High-Throughput Microfluidic Assays. AB - Motile bacteria navigate chemical environments by using chemoreceptors. The output of these protein sensors is linked to motility machinery and enables bacteria to follow chemical gradients. Understanding the chemical specificity of different families of chemoreceptors is essential for predicting and controlling bacterial behavior in ecological niches, including symbiotic and pathogenic interactions with plants and mammals. The identification of chemical(s) recognized by specific families of receptors is limited by the low throughput and complexity of chemotaxis assays. To address this challenge, we developed a microfluidic-based chemotaxis assay that is quantitative, simple, and enables high-throughput measurements of bacterial response to different chemicals. Using the model bacterium Escherichia coli, we demonstrated a strategy for identifying molecules that activate chemoreceptors from a diverse compound library and for determining how global behavioral strategies are tuned to chemical environments. PMID- 26285784 TI - Azathioprine lacks efficacy in hidradenitis suppurativa: a retrospective study of nine patients. PMID- 26285786 TI - Tissue Distribution Dynamics of Human NK Cells Inferred from Peripheral Blood Depletion Kinetics after Sphingosine-1-Phosphate Receptor Blockade. AB - Human natural killer (NK) cell subsets differentially distribute throughout the organism. While CD56(dim) and CD56(bright) NK cell subsets similarly reside in the bone marrow (BM), the CD56(dim) population predominantly accumulates in non lymphoid tissues and the CD56(bright) counterpart in lymphoid tissue (LT). The dynamics with which these NK cell subsets redistribute to tissues remains unexplored. Here, we studied individuals newly exposed to fingolimod, a drug that efficiently blocks sphingosine-1-phosphate (S1P)-directed lymphocyte - including NK cell - egress from tissue to blood. During an observation period of 6h peripheral blood depletion of CD56(bright) NK cells was observed 3 h after first dose of fingolimod, with 40-50% depletion after 6 h, while a decrease of the numbers of CD56(dim) NK cells did not reach the level of statistical significance. In vitro, CD56(bright) and CD56(dim) NK cells responded comparably to the BM-homing chemokine CXCL12, while CD56(bright) NK cells migrated more efficiently in gradients of the LT-homing chemokines CCL19 and CCL21. In conjuncture with these in vitro studies, the indirectly observed subset-specific depletion kinetics from blood are compatible with preferential and more rapid redistribution of CD56(bright) NK cells from blood to peripheral tissue such as LT and possibly also the inflamed central nervous system. These data shed light on an unexplored level at which access of NK cells to LT, and thus, for example antigen-presenting cells, is regulated. PMID- 26285787 TI - Selective amine labeling of cell surface proteins guided by coiled-coil assembly. AB - Covalent labeling of target proteins in living cells is useful for both fluorescence live-cell imaging and the subsequent biochemical analyses of the proteins. Here, we report an efficient method for the amine labeling of membrane proteins on the cell surface, guided by a noncovalent coiled-coil interaction. A carboxyl sulfosuccinimidyl ester introduced at the C-terminus of the coiled-coil probe reacted with target proteins under mild labeling conditions ([probe] = 150 nM, pH 7.4, 25 degrees C) for 20 min. Various fluorescent moieties with different hydrophobicities are available for covalent labeling with high signal/background labeling ratios. Using this method, oligomeric states of glycophorin A (GpA) were compared in mammalian CHO-K1 cells and sodium dodecyl sulfate (SDS) micelles. In the cell membranes, no significant self-association of GpA was detected, whereas SDS-PAGE suggested partial dimerization of the proteins. Membrane cholesterol was found to be an important factor that suppressed the dimerization of GpA. Thus, the covalent functionality enables direct comparison of the oligomeric state of membrane proteins under various conditions. (c) 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 484-490, 2016. PMID- 26285785 TI - Elastin Cables Define the Axial Connective Tissue System in the Murine Lung. AB - The axial connective tissue system is a fiber continuum of the lung that maintains alveolar surface area during changes in lung volume. Although the molecular anatomy of the axial system remains undefined, the fiber continuum of the lung is central to contemporary models of lung micromechanics and alveolar regeneration. To provide a detailed molecular structure of the axial connective tissue system, we examined the extracellular matrix of murine lungs. The lungs were decellularized using a 24 hr detergent treatment protocol. Systematic evaluation of the decellularized lungs demonstrated no residual cellular debris; morphometry demonstrated a mean 39 +/- 7% reduction in lung dimensions. Scanning electron microscopy (SEM) demonstrated an intact structural hierarchy within the decellularized lung. Light, fluorescence, and SEM of precision-cut lung slices demonstrated that alveolar duct structure was defined by a cable line element encased in basement membrane. The cable line element arose in the distal airways, passed through septal tips and inserted into neighboring blood vessels and visceral pleura. The ropelike appearance, collagenase resistance and anti-elastin immunostaining indicated that the cable was an elastin macromolecule. Our results indicate that the helical line element of the axial connective tissue system is composed of an elastin cable that not only defines the structure of the alveolar duct, but also integrates the axial connective tissue system into visceral pleura and peripheral blood vessels. PMID- 26285788 TI - Sodium glucose co-transporter inhibitors for the management of diabetes mellitus: an opinion paper from the Endocrine and Metabolism Practice and Research Network of the American College of Clinical Pharmacy. AB - Type 2 diabetes mellitus (T2DM) carries a high prevalence in the United States and worldwide. Therefore, the number of medication classes being developed and studied has grown. The individualized management of diabetes is accomplished by evaluating a medication's efficacy, safety, and cost, along with the patient's preference and tolerance to the medication. Sodium glucose co-transporter 2 inhibitors are a new therapeutic class indicated for the treatment of diabetes and have a unique mechanism of action, independent of beta-cell function. The first agent approved by the Food and Drug Administration (FDA) was canagliflozin in March 2013. Two agents - dapagliflozin and empagliflozin - were FDA-approved in January and July 2014, respectively. A clear understanding of the new class is needed to identify its appropriate use in clinical practice. Members of the American College of Clinical Pharmacy Endocrine and Metabolism Practice and Research Network reviewed available literature regarding this therapeutic class. The article addresses the advantages, disadvantages, emerging role, and patient education for sodium glucose co-transporter 2 inhibitors. Key limitations for this article include limited access to clinical trial data not published by the pharmaceutical company and limited data on products produced outside the United States. PMID- 26285790 TI - Retinal imaging with en face and cross-sectional optical coherence tomography delineates outer retinal changes in cancer-associated retinopathy secondary to Merkel cell carcinoma. AB - BACKGROUND: The study aims to correlate Fourier-domain optical coherence tomography (FD-OCT) with Goldmann visual field (GVF) to show the photoreceptor (PR) structure and function relationship in the first described case of cancer associated retinopathy (CAR) from Merkel cell carcinoma. FINDINGS: A case study of a patient with CAR who was imaged with serial GVF and FD-OCT over a 2-year period was carried out. En face images were created using a custom algorithm from the volumetric Fourier-domain OCT scans at the PR level. The areas of decreased PR reflectivity on the en face images were compared with GVF obtained at the same time point. Regions of reduced signal on en face scans corresponded with the position and shape of the GVF scotomas. Initially, the vision improved without PR changes. Cross-sectional OCTs showed early recovery of the outer nuclear layer and later improvement in the nerve fiber layer. Worsening vision corresponded with recurrence of the underlying cancer. Progressive global retinal atrophy was seen over time. CONCLUSIONS: Merkle cell carcinoma can cause CAR. Retinal function recovered without structural PR recovery. Transient vision improvements in treated CAR patients may be due to layers other than the PRs, but eventual vision decline results from significant progressive retinal atrophy. PMID- 26285789 TI - Does Molecular Genotype Provide Useful Information in the Management of Radioiodine Refractory Thyroid Cancers? Results of a Retrospective Study. AB - INTRODUCTION: Whether mutation status should be used to guide therapy is an important issue in many cancers. We correlated mutation profile in radioiodine refractory (RAIR) metastatic thyroid cancers (TCs) with patient outcome and response to tyrosine kinase inhibitors (TKIs), and discussed the results with other published data. MATERIALS AND METHODS: Outcome in 82 consecutive patients with metastatic RAIR thyroid carcinoma prospectively tested for BRAF, RAS and PI3KCA mutations was retrospectively analyzed, including 55 patients treated with multikinase inhibitors. RESULTS: Papillary thyroid carcinomas (PTCs) were the most frequent histological subtype (54.9 %), followed by poorly differentiated thyroid carcinoma [PDTC] (30.5 %) and follicular thyroid carcinoma [FTC] (14.6 %). A genetic mutation was identified in 23 patients (28 %) and BRAF was the most frequently mutated gene (23 %). Median progression-free survival (PFS) on first line TKI treatment was 14.6 months (95% CI 9.9-18.4). BRAF mutation positively influenced median PFS, both in the entire TKI-treated cohort (median PFS 34.7 months versus 11.6 months; hazard ratio [HR] 0.29; 95% CI 0.09-0.98; p = 0.03) and in the TKI-treated PTC cohort (n = 22) [log-rank p = 0.086; HR 2.95; 95 % CI 0.81-10.70). However, in TKI-treated patients, PDTC histologic subtype was the only independent prognostic factor for PFS identified in the multivariate analysis (HR 2.36; 95% CI 1.01-5.54; p = 0.048). CONCLUSION: Patients with BRAF mutant PTC had a significantly longer PFS than BRAF wild-type when treated with TKIs. However, due to the small number of BRAF-mutant patients, further investigations are required, especially to understand the potential positive effect of BRAF mutations in RAIR TC patients while having a negative prognostic impact in RAI-sensitive PTC patients. PMID- 26285791 TI - Absolute configuration of NFAT-133, an aromatic polyketide with immunosuppressive and antidiabetic activity from actinomycetes. PMID- 26285792 TI - Who's picking up the bill? PMID- 26285795 TI - Femtosecond laser ablation-based mass spectrometry: An ideal tool for stoichiometric analysis of thin films. AB - An accurate and routinely available method for stoichiometric analysis of thin films is a desideratum of modern materials science where a material's properties depend sensitively on elemental composition. We thoroughly investigated femtosecond laser ablation-inductively coupled plasma-mass spectrometry (fs-LA ICP-MS) as an analytical technique for determination of the stoichiometry of thin films down to the nanometer scale. The use of femtosecond laser ablation allows for precise removal of material with high spatial and depth resolution that can be coupled to an ICP-MS to obtain elemental and isotopic information. We used molecular beam epitaxy-grown thin films of LaPd(x)Sb2 and T(')-La2CuO4 to demonstrate the capacity of fs-LA-ICP-MS for stoichiometric analysis and the spatial and depth resolution of the technique. Here we demonstrate that the stoichiometric information of thin films with a thickness of ~10 nm or lower can be determined. Furthermore, our results indicate that fs-LA-ICP-MS provides precise information on the thin film-substrate interface and is able to detect the interdiffusion of cations. PMID- 26285796 TI - Non-truncating LIFR mutation: causal for prominent congenital pain insensitivity phenotype with progressive vertebral destruction? AB - We present a Qatari family with two children who displayed a characteristic phenotype of congenital marked pain insensitivity with hypohidrosis and progressive aseptic destruction of joints and vertebrae resembling that of hereditary sensory and autonomic neuropathies (HSANs). The patients, aged 10 and 14, remained of uncertain genetic diagnosis until whole genome sequencing was pursued. Genome sequencing identified a novel homozygous C65S mutation in the LIFR gene that is predicted to markedly destabilize and alter the structure of a particular domain and consequently to affect the functionality of the whole multi domain LIFR protein. The C65S mutant LIFR showed altered glycosylation and an elevated expression level that might be attributed to a slow turnover of the mutant form. LIFR mutations have been reported in Stuve-Wiedemann syndrome (SWS), a severe autosomal recessive skeletal dysplasia often resulting in early death. Our patients share some clinical features of rare cases of SWS long-term survivors; however, they also phenocopy HSAN due to the marked pain insensitivity phenotype and progressive bone destruction. Screening for LIFR mutations might be warranted in genetically unresolved HSAN phenotypes. PMID- 26285798 TI - Optimized enzymatic colorimetric assay for determination of hydrogen peroxide (H2O2) scavenging activity of plant extracts. AB - The classical method to determine hydrogen peroxide (H2O2) scavenging activity of plant extracts is evaluated by measuring the disappearance of H2O2 at a wavelength of 230 nm. Since this method suffers from the interference of phenolics having strong absorption in the UV region, a simple and rapid colorimetric assay was developed where plant extracts are introduced to H2O2, phenol and 4-aminoantipyrine reaction system in the presence of horseradish peroxidase (HRP). This reaction yields a quinoneimine chromogen which can be measured at 504 nm. Decrease in the colour intensity reflects the H2O2 scavenged by the plant material. *Optimum conditions determined for this assay were 30 min reaction time, 37 degrees C, pH 7, enzyme concentration of 1 U/ml and H2O2 concentration of 0.7 mM. The limit of detection (LOD) and limit of quantitation (LOQ) were 136 MUM and 411 MUM, respectively.*Half maximal effective concentration required to scavenge 50% of H2O2 in the system (EC50 value) calculated for several plant extracts and standard antioxidants resulted in coefficient of variance (CV%) of the EC50 values less than 3.0% and correlation coefficient values (R (2)) > 0.95 for all dose response curves obtained.*This method is convenient and very precise which is suitable for the rapid quantification of H2O2 scavenging ability of standard antioxidants and natural antioxidants present in plant extracts. PMID- 26285797 TI - The Phosphorylation Profile of Myosin Binding Protein-C Slow is Dynamically Regulated in Slow-Twitch Muscles in Health and Disease. AB - Myosin Binding Protein-C slow (sMyBP-C) is expressed in skeletal muscles where it plays structural and regulatory roles. The functions of sMyBP-C are modulated through alternative splicing and phosphorylation. Herein, we examined the phosphorylation profile of sMyBP-C in mouse slow-twitch soleus muscle isolated from fatigued or non-fatigued young (2-4-months old) and old (~14-months old) wild type and mdx mice. Our findings are two-fold. First, we identified the phosphorylation events present in individual sMyBP-C variants at different states. Secondly, we quantified the relative abundance of each phosphorylation event, and of sMyBP-C phospho-species as a function of age and dystrophy, in the presence or absence of fatigue. Our results revealed both constitutive and differential phosphorylation of sMyBP-C. Moreover, we noted a 10-40% and a 25-35% reduction in the phosphorylation levels of select sites in old wild type and young or old mdx soleus muscles, respectively. On the contrary, we observed a 5 10% and a 20-25% increase in the phosphorylation levels of specific sites in young fatigued wild type and mdx soleus muscles, respectively. Overall, our studies showed that the phosphorylation pattern of sMyBP-C is differentially regulated following reversible (i.e. fatigue) and non-reversible (i.e. age and disease) (patho)physiological stressors. PMID- 26285799 TI - The Physiologic Impact of Unilateral Recurrent Laryngeal Nerve (RLN) Lesion on Infant Oropharyngeal and Esophageal Performance. AB - Recurrent laryngeal nerve (RLN) injury in neonates, a complication of patent ductus arteriosus corrective surgery, leads to aspiration and swallowing complications. Severity of symptoms and prognosis for recovery are variable. We transected the RLN unilaterally in an infant mammalian animal model to characterize the degree and variability of dysphagia in a controlled experimental setting. We tested the hypotheses that (1) both airway protection and esophageal function would be compromised by lesion, (2) given our design, variability between multiple post-lesion trials would be minimal, and (3) variability among individuals would be minimal. Individuals' swallowing performance was assessed pre- and post-lesion using high speed VFSS. Aspiration was assessed using the Infant Mammalian Penetration-Aspiration Scale (IMPAS). Esophageal function was assessed using two measures devised for this study. Our results indicate that RLN lesion leads to increased frequency of aspiration, and increased esophageal dysfunction, with significant variation in these basic patterns at all levels. On average, aspiration worsened with time post-lesion. Within a single feeding sequence, the distribution of unsafe swallows varied. Individuals changed post lesion either by increasing average IMPAS score, or by increasing variation in IMPAS score. Unilateral RLN transection resulted in dysphagia with both compromised airway protection and esophageal function. Despite consistent, experimentally controlled injury, significant variation in response to lesion remained. Aspiration following RLN lesion was due to more than unilateral vocal fold paralysis. We suggest that neurological variation underlies this pattern. PMID- 26285800 TI - Investigation of Human Cancers for Retrovirus by Low-Stringency Target Enrichment and High-Throughput Sequencing. AB - Although nearly one fifth of all human cancers have an infectious aetiology, the causes for the majority of cancers remain unexplained. Despite the enormous data output from high-throughput shotgun sequencing, viral DNA in a clinical sample typically constitutes a proportion of host DNA that is too small to be detected. Sequence variation among virus genomes complicates application of sequence specific, and highly sensitive, PCR methods. Therefore, we aimed to develop and characterize a method that permits sensitive detection of sequences despite considerable variation. We demonstrate that our low-stringency in-solution hybridization method enables detection of <100 viral copies. Furthermore, distantly related proviral sequences may be enriched by orders of magnitude, enabling discovery of hitherto unknown viral sequences by high-throughput sequencing. The sensitivity was sufficient to detect retroviral sequences in clinical samples. We used this method to conduct an investigation for novel retrovirus in samples from three cancer types. In accordance with recent studies our investigation revealed no retroviral infections in human B-cell lymphoma cells, cutaneous T-cell lymphoma or colorectal cancer biopsies. Nonetheless, our generally applicable method makes sensitive detection possible and permits sequencing of distantly related sequences from complex material. PMID- 26285801 TI - Histone H3K4me3 and H3K27me3 regulatory genes control stable transmission of an epimutation in rice. AB - DNA methylation loss can produce inheritable active epialleles in plants. The mechanism involved in the stable transmission of hypomethylated epimuations is presently not clear. Here we show that maintenance of a stably hypomethylated active epiallele in rice required a CHD3 protein (CHR729) and that over expression of an H3K4me3 demethylase (JMJ703) or H3K27me3 methyltransferase (SDG711) could stably resilence the epiallele. CHR729 and JMJ703 have antagonistic function in H3K4me3 in maintaining the active state of the epiallele, whereas SDG711-mediated H3K27me3 was sufficient to stably repress the locus. The data suggest that H3K4me3 and H3K27me3 controlled by these chromatin regulators may be involved in stable transmission/resetting of epigenetic variation in rice. PMID- 26285803 TI - PvD1 defensin, a plant antimicrobial peptide with inhibitory activity against Leishmania amazonensis. AB - Plant defensins are small cysteine-rich peptides and exhibit antimicrobial activity against a variety of both plant and human pathogens. Despite the broad inhibitory activity that plant defensins exhibit against different micro organisms, little is known about their activity against protozoa. In a previous study, we isolated a plant defensin named PvD1 from Phaseolus vulgaris (cv. Perola) seeds, which was seen to be deleterious against different yeast cells and filamentous fungi. It exerted its effects by causing an increase in the endogenous production of ROS (reactive oxygen species) and NO (nitric oxide), plasma membrane permeabilization and the inhibition of medium acidification. In the present study, we investigated whether PvD1 could act against the protozoan Leishmania amazonensis. Our results show that, besides inhibiting the proliferation of L. amazonensis promastigotes, the PvD1 defensin was able to cause cytoplasmic fragmentation, formation of multiple cytoplasmic vacuoles and membrane permeabilization in the cells of this organism. Furthermore, we show, for the first time, that PvD1 defensin was located within the L. amazonensis cells, suggesting the existence of a possible intracellular target. PMID- 26285804 TI - Effect of BIX-01294 on H3K9me2 levels and the imprinted gene Snrpn in mouse embryonic fibroblast cells. AB - Histone H3 lysine 9 dimethylation (H3K9me2) hypermethylation is thought to be a major influential factor in cellular reprogramming, such as somatic cell nuclear transfer (SCNT) and induction of pluripotent stem cells (iPSCs). The diazepin quinazolin-amine derivative (BIX-01294) specifically inhibits the activity of histone methyltransferase EHMT2 (euchromatic histone-lysine N-methyltransferase 2) and reduces H3K9me2 levels in cells. The imprinted gene small nuclear ribonucleoprotein N (Snrpn) is of particular interest because of its important biological functions. The objective of the present study was to investigate the effect of BIX-01294 on H3K9me2 levels and changes in Snrpn DNA methylation and histone H3K9me2 in mouse embryonic fibroblasts (MEFs). Results showed that 1.3 MUM BIX-01294 markedly reduced global levels of H3K9me2 with almost no cellular toxicity. There was a significant decrease in H3K9me2 in promoter regions of the Snrpn gene after BIX-01294 treatment. A significant increase in methylation of the Snrpn differentially methylated region 1 (DMR1) and slightly decreased transcript levels of Snrpn were found in BIX-01294-treated MEFs. These results suggest that BIX-01294 may reduce global levels of H3K9me2 and affect epigenetic modifications of Snrpn in MEFs. PMID- 26285806 TI - Washington State Opioid Prescribing Guidelines. PMID- 26285807 TI - Adjunctive Systemic and Local Antimicrobial Therapy in the Surgical Treatment of Peri-implantitis: A Randomized Controlled Clinical Trial. AB - The aim of the present randomized controlled clinical trial was to investigate the adjunctive effect of systemic antibiotics and the local use of chlorhexidine for implant surface decontamination in the surgical treatment of peri implantitis. One hundred patients with severe peri-implantitis were recruited. Surgical therapy was performed with or without adjunctive systemic antibiotics or the local use of chlorhexidine for implant surface decontamination. Treatment outcomes were evaluated at 1 y. A binary logistic regression analysis was used to identify factors influencing the probability of treatment success, that is, probing pocket depth <=5 mm, absence of bleeding/suppuration on probing, and no additional bone loss. Treatment success was obtained in 45% of all implants but was higher in implants with a nonmodified surface (79%) than those with a modified surface (34%). The local use of chlorhexidine had no overall effect on treatment outcomes. While adjunctive systemic antibiotics had no impact on treatment success at implants with a nonmodified surface, a positive effect on treatment success was observed at implants with a modified surface. The likelihood for treatment success using adjunctive systemic antibiotics in patients with implants with a modified surface, however, was low. As the effect of adjunctive systemic antibiotics depended on implant surface characteristics, recommendations for their use in the surgical treatment of peri-implantitis should be based on careful assessments of the targeted implant (ClinicalTrials.gov NCT01857804). PMID- 26285808 TI - Wnt Signaling and Its Contribution to Craniofacial Tissue Homeostasis. AB - A new field of dental medicine seeks to exploit nature's solution for repairing damaged tissues, through the process of regeneration. Most adult mammalian tissues have limited regenerative capacities, but in lower vertebrates, the molecular machinery for regeneration is an elemental part of their genetic makeup. Accumulating data suggest that the molecular pathways responsible for the regenerative capacity of teleosts, amphibians, and reptiles have fallen into disuse in mammals but that they can be "jumpstarted" by the selective activation of key molecules. The Wnt family of secreted proteins constitutes one such critical pathway: Wnt proteins rank among the most potent and ubiquitous stem cell self-renewing factors, with tremendous potential for promoting human tissue regeneration. Wnt reporter and lineage-tracing strains of mice have been employed to create molecular maps of Wnt responsiveness in the craniofacial tissues, and these patterns of Wnt signaling colocalize with stem/progenitor populations in the rodent incisor apex, the dental pulp, the alveolar bone, the periodontal ligament, the cementum, and oral mucosa. The importance of Wnt signaling in both the maintenance and healing of these craniofacial tissues is summarized, and the therapeutic potential of Wnt-based strategies to accelerate healing through activation of endogenous stem cells is highlighted. PMID- 26285805 TI - The cellular response to vascular endothelial growth factors requires co ordinated signal transduction, trafficking and proteolysis. AB - VEGFs (vascular endothelial growth factors) are a family of conserved disulfide linked soluble secretory glycoproteins found in higher eukaryotes. VEGFs mediate a wide range of responses in different tissues including metabolic homoeostasis, cell proliferation, migration and tubulogenesis. Such responses are initiated by VEGF binding to soluble and membrane-bound VEGFRs (VEGF receptor tyrosine kinases) and co-receptors. VEGF and receptor splice isoform diversity further enhances complexity of membrane protein assembly and function in signal transduction pathways that control multiple cellular responses. Different signal transduction pathways are simultaneously activated by VEGFR-VEGF complexes with membrane trafficking along the endosome-lysosome network further modulating signal output from multiple enzymatic events associated with such pathways. Balancing VEGFR-VEGF signal transduction with trafficking and proteolysis is essential in controlling the intensity and duration of different intracellular signalling events. Dysfunction in VEGF-regulated signal transduction is important in chronic disease states including cancer, atherosclerosis and blindness. This family of growth factors and receptors is an important model system for understanding human disease pathology and developing new therapeutics for treating such ailments. PMID- 26285809 TI - Ex Vivo Modeling of Multidomain Peptide Hydrogels with Intact Dental Pulp. AB - Preservation of a vital dental pulp is a central goal of restorative dentistry. Currently, there is significant interest in the development of tissue engineering scaffolds that can serve as biocompatible and bioactive pulp-capping materials, driving dentin bridge formation without causing cytotoxic effects. Our earlier in vitro studies described the biocompatibility of multidomain peptide (MDP) hydrogel scaffolds with dental pulp-derived cells but were limited in their ability to model contact with intact 3-dimensional pulp tissues. Here, we utilize an established ex vivo mandible organ culture model to model these complex interactions. MDP hydrogel scaffolds were injected either at the interface of the odontoblasts and the dentin or into the pulp core of mandible slices and subsequently cultured for up to 10 d. Histology reveals minimal disruption of tissue architecture adjacent to MDP scaffolds injected into the pulp core or odontoblast space. Additionally, the odontoblast layer is structurally preserved in apposition to the MDP scaffold, despite being separated from the dentin. Alizarin red staining suggests mineralization at the periphery of MDP scaffolds injected into the odontoblast space. Immunohistochemistry reveals deposition of dentin sialophosphoprotein by odontoblasts into the adjacent MDP hydrogel, indicating continued functionality. In contrast, no mineralization or dentin sialophosphoprotein deposition is evident around MDP scaffolds injected into the pulp core. Collagen III expression is seen in apposition to gels at all experimental time points. Matrix metalloproteinase 2 expression is observed associated with centrally injected MDP scaffolds at early time points, indicating proteolytic digestion of scaffolds. Thus, MDP scaffolds delivered centrally and peripherally within whole dental pulp tissue are shown to be biocompatible, preserving local tissue architecture. Additionally, odontoblast function and pulp vitality are sustained when MDP scaffolds are intercalated between dentin and the odontoblast region, a finding that has significant implications when considering these materials as pulp-capping agents. PMID- 26285810 TI - Stem Cell-Soluble Signals Enhance Multilumen Formation in SMG Cell Clusters. AB - Saliva plays a major role in maintaining oral health. Patients with salivary hypofunction exhibit difficulty in chewing and swallowing foods, tooth decay, periodontal disease, and microbial infections. At this time, treatments for hyposalivation are limited to medications (e.g., muscarinic receptor agonists: pilocarpine and cevimeline) that induce saliva secretion from residual acinar cells as well as artificial salivary substitutes. Therefore, advancement of restorative treatments is necessary to improve the quality of life in these patients. Our previous studies indicated that salivary cells are able to form polarized 3-dimensional structures when grown on growth factor-reduced Matrigel. This basement membrane is rich in laminin-III (L1), which plays a critical role in salivary gland formation. Mitotically inactive feeder layers have been used previously to support the growth of many different cell types, as they provide factors necessary for cell growth and organization. The goal of this study was to improve salivary gland cell differentiation in primary cultures by using a combination of L1 and a feeder layer of human hair follicle-derived mesenchymal stem cells (hHF-MSCs). Our results indicated that the direct contact of mouse submandibular (mSMG) cell clusters and hHF-MSCs was not required for mSMG cells to form acinar and ductal structures. However, the hHF-MSC conditioned medium enhanced cell organization and multilumen formation, indicating that soluble signals secreted by hHF-MSCs play a role in promoting these features. PMID- 26285811 TI - Induced Pluripotent Stem Cells: A New Frontier for Stem Cells in Dentistry. AB - Induced pluripotent stem cells (iPSCs) are the newest member of a growing list of stem cell populations that hold great potential for use in cell-based treatment approaches in the dental field. This review summarizes the dental tissues that have successfully been utilized to generate iPSC lines, as well as the potential uses of iPSCs for tissue regeneration in different dental applications. While iPSCs display great promise in a number of dental applications, there are safety concerns with these cells that need to be addressed before they can be used in clinical settings. This review outlines some of the apprehensions to the use of iPSCs clinically, and it details approaches that are being employed to ensure the safety and efficacy of these cells. One of the major approaches being investigated is the differentiation of iPSCs prior to use in patients. iPSCs have successfully been differentiated into a wide range of cells and tissue types. This review focuses on 2 differentiation approaches-the differentiation of iPSCs into mesenchymal stem cells and the differentiation of iPSCs into osteoprogenitor cells. Both these resulting populations of cells are particularly relevant to the dental field. PMID- 26285813 TI - Androgen actions via androgen receptor promote PTEN inactivation induced uterine cancer. AB - Haploinsufficient inactivating phosphatase and tensin homolog (Pten) mutations cause Cowden syndrome, an autosomal dominant risk genotype for hormone dependent reproductive cancers. As androgen actions mediated via the androgen receptor (AR) supports uterine growth and may modify uterine cancer risk, we hypothesized that a functional AR may increase PTEN inactivation induced uterine cancer. To test the hypothesis, we compared the PTEN knockout (PTENKO) induced uterine pathology in heterozygous PTENKO and combined heterozygous PTEN and complete AR knockout (PTENARKO) female mice. PTENKO induced uterine pathology was significantly reduced by AR inactivation with severe macroscopic uterine pathology present in 21% of PTENARKO vs 46% of PTENKO at a median age of 45 weeks. This could be due to reduced stroma ERalpha expression in PTENARKO compared to PTENKO uterus, while AR inactivation did not modify PTEN or P-AKT levels. Unexpectedly, while progesterone (P4) is assumed protective in uterine cancers, serum P4 was significantly higher in PTENKO females compared to WT, ARKO, and PTENARKO females consistent with more corpora lutea in PTENKO ovaries. Serum testosterone and ovarian estradiol were similar between all females. Hence, our results demonstrated AR inactivation mediated protection against PTENKO induced uterine pathology and suggests a potential role for antiandrogens in uterine cancer prevention and treatment. PMID- 26285812 TI - Salivary Glands: Stem Cells, Self-duplication, or Both? AB - Understanding the intrinsic potential for renewal and regeneration within a tissue is critical for the rational design of reparative strategies. Maintenance of the salivary glands is widely thought to depend on the differentiation of stem cells. However, there is also new evidence that homeostasis of the salivary glands, like that of the liver and pancreas, relies on self-renewal of differentiated cells rather than a stem cell pool. Here, we review the evidence for both modes of turnover and consider the implications for the process of regeneration. We propose that the view of salivary glands as postmitotic and dependent on stem cells for renewal be revised to reflect the proliferative activity of acinar cells and their role in salivary gland homeostasis. PMID- 26285815 TI - RAS proto-oncogene in medullary thyroid carcinoma. AB - Medullary thyroid carcinoma (MTC) is a rare malignancy originating from the calcitonin-secreting parafollicular thyroid C cells. Approximately 75% of cases are sporadic. Rearranged during transfection (RET) proto-oncogene plays a crucial role in MTC development. Besides RET, other oncogenes commonly involved in the pathogenesis of human cancers have also been investigated in MTC. The family of human RAS genes includes the highly homologous HRAS, KRAS, and NRAS genes that encode three distinct proteins. Activating mutations in specific hotspots of the RAS genes are found in about 30% of all human cancers. In thyroid neoplasias, RAS gene point mutations, mainly in NRAS, are detected in benign and malignant tumors arising from the follicular epithelium. However, recent reports have also described RAS mutations in MTC, namely in HRAS and KRAS. Overall, the prevalence of RAS mutations in sporadic MTC varies between 0-43.3%, occurring usually in tumors with WT RET and rarely in those harboring a RET mutation, suggesting that activation of these proto-oncogenes represents alternative genetic events in sporadic MTC tumorigenesis. Thus, the assessment of RAS mutation status can be useful to define therapeutic strategies in RET WT MTC. MTC patients with RAS mutations have an intermediate risk for aggressive cancer, between those with RET mutations in exons 15 and 16, which are associated with the worst prognosis, and cases with other RET mutations, which have the most indolent course of the disease. Recent results from exome sequencing indicate that, besides mutations in RET, HRAS, and KRAS, no other recurrent driver mutations are present in MTC. PMID- 26285814 TI - Novel somatic mutations and distinct molecular signature in aldosterone-producing adenomas. AB - Aldosterone-producing adenomas (APAs) are found in 1.5-3.0% of hypertensive patients in primary care and can be cured by surgery. Elucidation of genetic events may improve our understanding of these tumors and ultimately improve patient care. Approximately 40% of APAs harbor a missense mutation in the KCNJ5 gene. More recently, somatic mutations in CACNA1D, ATP1A1 and ATP2B3, also important for membrane potential/intracellular Ca(2) (+) regulation, were observed in APAs. In this study, we analyzed 165 APAs for mutations in selected regions of these genes. We then correlated mutational findings with clinical and molecular phenotype using transcriptome analysis, immunohistochemistry and semiquantitative PCR. Somatic mutations in CACNA1D in 3.0% (one novel mutation), ATP1A1 in 6.1% (six novel mutations) and ATP2B3 in 3.0% (two novel mutations) were detected. All observed mutations were located in previously described hotspot regions. Patients with tumors harboring mutations in CACNA1D, ATP1A1 and ATP2B3 were operated at an older age, were more often male and had tumors that were smaller than those in patients with KCNJ5 mutated tumors. Microarray transcriptome analysis segregated KCNJ5 mutated tumors from ATP1A1/ATP2B3 mutated tumors and those without mutation. We observed significant transcription upregulation of CYP11B2, as well as the previously described glomerulosa-specific gene NPNT, in ATP1A1/ATP2B3 mutated tumors compared to KCNJ5 mutated tumors. In summary, we describe novel somatic mutations in proteins regulating the membrane potential/intracellular Ca(2) (+) levels, and also a distinct mRNA and clinical signature, dependent on genetic alteration. PMID- 26285816 TI - Qualitative website analysis of information on birth after caesarean section. AB - BACKGROUND: The United Kingdom (UK) caesarean section (CS) rate is largely determined by reluctance to augment trial of labour and vaginal birth. Choice between repeat CS and attempting vaginal birth after CS (VBAC) in the next pregnancy is challenging, with neither offering clear safety advantages. Women may access online information during the decision-making process. Such information is known to vary in its support for either mode of birth when assessed quantitatively. Therefore, we sought to explore qualitatively, the content and presentation of web-based health care information on birth after caesarean section (CS) in order to identify the dominant messages being conveyed. METHODS: The search engine GoogleTM was used to conduct an internet search using terms relating to birth after CS. The ten most frequently returned websites meeting relevant purposive sampling criteria were analysed. Sampling criteria were based upon funding source, authorship and intended audience. Images and written textual content together with presence of links to additional media or external web content were analysed using descriptive and thematic analyses respectively. RESULTS: Ten websites were analysed: five funded by Government bodies or professional membership; one via charitable donations, and four funded commercially. All sites compared the advantages and disadvantages of both repeat CS and VBAC. Commercially funded websites favoured a question and answer format alongside images, 'pop-ups', social media forum links and hyperlinks to third party sites. The relationship between the parent sites and those being linked to may not be readily apparent to users, risking perception of endorsement of either VBAC or repeat CS whether intended or otherwise. Websites affiliated with Government or health services presented referenced clinical information in a factual manner with podcasts of real life experiences. Many imply greater support for VBAC than repeat CS although this was predominantly conveyed through subtle use of words rather than overt messages, with the exception of the latter being apparent in one site. CONCLUSIONS: Websites providing information on birth after CS appear to vary in nature of content according to their funding source. The most user-friendly, balanced and informative websites appear to be those funded by government agencies. PMID- 26285817 TI - Outcomes after minimally invasive lumbar decompression: a biomechanical comparison of unilateral and bilateral laminotomies. AB - BACKGROUND: The unilateral approach for bilateral decompression was developed as an alternative to laminectomy. Unilateral laminotomy has been rated technically considerably more demanding and associated with more perioperative complications than bilateral laminotomy. Several studies have indicated that bilateral laminotomy are associated with a substantial benefit in most outcome parameters and thus constituted a promising treatment alternative. However, no complete kinematic data and relative biomechanical analysis for evaluating spinal instability treated with unilateral and bilateral laminotomy are available. Therefore, the purpose of this study was to compare the stability of various decompression methods. METHODS: Ten porcine lumbar spines were biomechanically evaluated regarding their strain and range of motion, and the results were compared following unilateral or bilateral laminotomies and laminectomy. The experimental protocol included flexion and extension in the following procedures: intact, unilateral or bilateral laminotomies (L2-L5), and full laminectomy (L2 L5). The spinal segment kinematics was captured using a motion tracking system, and the strain was measured using a strain gauge. RESULTS: No significant differences were observed during flexion and extension between the unilateral and bilateral laminotomies, whereas laminectomy yielded statistically significant findings. Regarding strain, significant differences were observed between the laminectomy and other groups. These results suggest that laminotomy entails higher spinal stability than laminectomy, with no significant differences between bilateral and unilateral laminotomies. CONCLUSIONS: The laminectomy group exhibited more instability, including the index of the range of motion and strain. However, bilateral laminotomy seems to have led to stability similar to that of unilateral laminotomy according to our short-term follow-up. In addition, performing bilateral laminotomies is easier for surgeons than adopting a unilateral approach for bilateral decompression. The results provide recommendations for surgeons regarding final decision making. Future studies conducting long-term evaluation are required. PMID- 26285818 TI - A qualitative study on the ethics of transforming care: examining the development and implementation of Canada's first mental health strategy. AB - BACKGROUND: The Mental Health Commission of Canada worked collaboratively with stakeholders to create a new framework for a federal mental health strategy, which is now mandated for implementation by 2017. The proposed strategies have been written into provincial health plans, hospital accreditation standards, and the annual objectives of psychiatric departments and community organizations. This project will explore the decision-making process among those who contributed to Canada's first federal mental health policy and those implementing this policy in the clinical setting. Despite the centrality of ethical reasoning to the successful uptake of the recent national guidelines for recovery-oriented care, to date, there are no studies focused exclusively on the ethical tensions that emerged and continue to emerge during the creation and implementation of the new standards for recovery-oriented practice. METHODS/DESIGN: This two-year Canadian Institute of Health Research Catalyst Grant in Ethics (2015-2017) consists of three components. C-I, a retrospective, qualitative study consisting of document analysis and interviews with key policy-makers of the ethical tensions that arose during the development of Canada's Mental Health Strategy will be conducted in parallel to C-II, a theory-based, focused ethnography of how mental health practitioners in a psychiatric setting reason about and act upon new standards in everyday practice. Case-based scenarios of ethical tensions will be developed from C-I/II and fed-forward to C-III: participatory forums with policy-makers, mental health practitioners, and other stakeholders in recovery-oriented services to collectively identify and prioritize key ethical concerns and generate action steps to close the gap between the policy-making process and its implementation at the local level. DISCUSSION: Policy-makers and clinicians make important everyday decisions that effect the creation and implementation of new practice standards. Particularly, there is a need to understand how ethical dilemmas that arise during this decision-making process and the reasoning and resources they use to resolve these tensions impact on the implementation process. This catalyst grant in ethics will (1) introduce a novel line of inquiry focusing on the ethical tensions that arose in the development of Canada's first mental health strategy, while (2) intensifying our focus on the ethical aspects of moving policy into action. PMID- 26285819 TI - Standardised outcomes in nephrology - Haemodialysis (SONG-HD): study protocol for establishing a core outcome set in haemodialysis. AB - BACKGROUND: Chronic kidney disease is a significant contributor to mortality and morbidity worldwide, and the number of people who require dialysis or transplantation continues to increase. People on dialysis are 15 times more likely to die than the general population. Dialysis is also costly, intrusive, and time-consuming and imposes an enormous burden on patients and their families. This escalating problem has spurred a proliferation of trials in dialysis, yet health and quality of life remain poor. The reasons for this are complex and varied but are attributable in part to problems in the design and reporting of studies, particularly outcome selection. Problems related to outcomes include use of unvalidated surrogates, outcomes of little or no relevance to patients, highly variable outcome selection limiting comparability across studies, and bias in reporting outcomes. The aim of the Standardised Outcomes in Nephrology Haemodialysis (SONG-HD) study is to establish a core outcome set for haemodialysis trials, to improve the quality of reporting, and the relevance of trials conducted in people on haemodialysis. METHODS/DESIGN: SONG-HD is a five phase project that includes the following: a systematic review to identify outcomes that have been reported in haemodialysis systematic reviews and trials; nominal group technique with patients and caregivers to identify, rank, and describe reasons for their choices; qualitative stakeholder interviews with patients, caregivers, clinicians, researchers, and policy makers to elicit individual values and perspectives on outcomes for haemodialysis trials; a three round Delphi survey with stakeholder groups to distil and generate a prioritised list of core outcomes; and a consensus workshop to establish a core outcome set for haemodialysis trials. DISCUSSION: Establishing a core outcome set to be consistently measured and reported in haemodialysis trials will improve the integrity, transparency, usability, and contribution of research relevant to patients requiring haemodialysis; ensure that outcomes of relevance to all stakeholders are consistently reported across trials; and mitigate against outcome reporting bias. Ultimately, patients will be more protected from potential harm, patients and clinicians will be better able to make informed decisions about treatment, and researchers and policy makers will be more able to maximise the value of research to the public. PMID- 26285820 TI - Contribution of the non-effector members of the HrpL regulon, iaaL and matE, to the virulence of Pseudomonas syringae pv. tomato DC3000 in tomato plants. AB - BACKGROUND: The phytohormone indole-3-acetic acid (IAA) is widely distributed among plant-associated bacteria. Certain strains of the Pseudomonas syringae complex can further metabolize IAA into a less biologically active amino acid conjugate, 3-indole-acetyl-epsilon-L-lysine, through the action of the iaaL gene. In P. syringae and Pseudomonas savastanoi strains, the iaaL gene is found in synteny with an upstream gene, here called matE, encoding a putative MATE family transporter. In P. syringae pv. tomato (Pto) DC3000, a pathogen of tomato and Arabidopsis plants, the HrpL sigma factor controls the expression of a suite of virulence-associated genes via binding to hrp box promoters, including that of the iaaL gene. However, the significance of HrpL activation of the iaaL gene in the virulence of Pto DC3000 is still unclear. RESULTS: A conserved hrp box motif is found upstream of the iaaL gene in the genomes of P. syringae strains. However, although the promoter region of matE is only conserved in genomospecies 3 of this bacterial group, we showed that this gene also belongs to the Pto DC3000 HrpL regulon. We also demonstrated that the iaaL gene is transcribed both independently and as part of an operon with matE in this pathogen. Deletion of either the iaaL or the matE gene resulted in reduced fitness and virulence of Pto DC3000 in tomato plants. In addition, we used multicolor fluorescence imaging to visualize the responses of tomato plants to wild-type Pto DC3000 and to its DeltamatE and DeltaiaaL mutants. Activation of secondary metabolism prior to the development of visual symptoms was observed in tomato leaves after bacterial challenges with all strains. However, the observed changes were strongest in plants challenged by the wild-type strain, indicating lower activation of secondary metabolism in plants infected with the DeltamatE or DeltaiaaL mutants. CONCLUSIONS: Our results provide new evidence for the roles of non-type III effector genes belonging to the Pto DC3000 HrpL regulon in virulence. PMID- 26285821 TI - Radial endobronchial ultrasound in diagnosing peripheral lung lesions in a high tuberculosis setting. AB - BACKGROUND: Current data for the utility of radial endobronchial ultrasound (EBUS) in investigating peripheral lung lesions (PLLs) has been restricted to populations with low pulmonary tuberculosis (TB) incidence. The aim of this study was to assess the diagnostic utility of radial EBUS with guide sheath in the diagnosis of peripheral lung lesions in Singapore, a high TB incidence setting. METHODS: A post-hoc database analysis was performed. 123 consecutive patients with computed tomographic evidence of PLLs who underwent radial EBUS guided bronchoscopy were included. RESULTS: The final diagnosis was malignancy in 76 cases and benign in 44 cases. Radial EBUS guided bronchoscopy had a sensitivity of 65.8 % for malignancy, positive predictive value of 100 %, negative predictive value of 62.9 %, and a diagnostic accuracy of 82.5 %. 22 patients had a final diagnosis of pulmonary TB. The diagnostic sensitivity for pulmonary TB was 77.3 %, with a positive predictive value of 100 %, negative predictive value of 95.2 % and a diagnostic accuracy of 95.8 %. Overall, 58.8 % of pulmonary TB cases relied on histology to make an early diagnosis. CONCLUSION: Radial EBUS guided bronchosopy is useful in investigating PLLs in a high TB incidence setting. Our data also suggests that radial EBUS is a more rapid diagnosis technique for tuberculous lesions. PMID- 26285822 TI - Displacements prediction from 3D finite element model of maxillary protraction with and without rapid maxillary expansion in a patient with unilateral cleft palate and alveolus. AB - BACKGROUND: Both maxillary protraction and rapid expansion are recommended for patients with cleft palate and alveolus. The aim of the study is to establish a three-dimensional finite element model of the craniomaxillary complex with unilateral cleft palate and alveolus to simulate maxillary protraction with and without rapid maxillary expansion. The study also investigates the deformation of the craniomaxillary complex after applied orthopaedic forces in different directions. METHODS: A three dimensional finite element model of 1,277,568 hexahedral elements (C3D8) and 1,801,945 nodes was established based upon CT scan of a patient with unilateral cleft palate and alveolus on the right side in this study. A force of 4.9 N per side was directed on the anatomic height of contour on the buccal side of the first molar. The angles between the force vector and occlusal plane were -30 degrees , -20 degrees , -10 degrees , 0 degrees , 10 degrees , 20 degrees , and 30 degrees . A force of 2.45 N on each loading point was directed on the anatomic height of contour on the lingual side of the first premolar and the first molar to simulate the expansion of the palate. RESULTS: The craniomaxillary complex displaced forward under any of the loading conditions. The sagittal and vertical displacement of the craniomaxillary complex reached their peak at the protraction degree of -10 degrees forward and downward to the occlusal plane. There were larger sagittal displacements when the maxilla was protracted forward with maxillary expansion. The palatal plane rotated counterclockwise under any of the loading conditions. Being protracted without expansion, the dental arch was constricted. When supplemented with maxillary expansion, the width of the dental arch increased. Transverse deformation of the dental arch on affected side was different from that on unaffected side. CONCLUSIONS: Protraction force alone led the craniomaxillary complex moved forward and counterclockwise, accompanied with lateral constrain on the dental arch. Additional rapid maxillary expansion resulted in a more positive reaction including both larger sagittal displacement and the width of the dental arch increase. PMID- 26285823 TI - Role for intravesical prostatic protrusion in lower urinary tract symptom: a fluid structural interaction analysis study. AB - BACKGROUND: Numerous studies indicated that Intravesical prostatic protrusion is relevant to prognosis of LUTS, however, the confounding effect that is brought about by prostate volume, urethra anterior curvature angle and other factors makes it hard to evaluate the role of intravesical prostatic protrusion in clinical observation. METHODS: We proposed a fluid structural interaction analysis approach. 3D models were constructed based on MRI images, and prostatic urethra diameters were calibrated with urodynamic data. Comparisons of urine flow dynamics were made between models with various degree of intravesical prostatic protrusion, while the intravesical pressure, anterior urethra curvature angle and diameter of prostatic urethra were same among all models to rule out their confounding effects. RESULTS: Simulation result showed that the decrement of diameter and increment of variation in cross-sectional area for prostatic urethra were related to the degree of intravesical prostatic protrusion. Such deformation would lead to deterioration of flow efficiency and could compromise the effect of bladder outlet obstruction alleviation treatment. CONCLUSIONS: These results provided further evidence for intravesical prostatic protrusion being an independent risk factor for bladder outlet obstruction severity and demonstrated that intravesical prostatic protrusion would be a promising marker in clinical decision making. PMID- 26285824 TI - Compliance with Surgical Safety Checklist completion in the operating room of University of Gondar Hospital, Northwest Ethiopia. AB - BACKGROUND: Appropriate utilization and compliance of Surgical Safety Checklist reduces occurrence of perioperative surgical complications and improve patient outcomes. However, data on compliance of surgical checklists are scarce in the study area. Therefore, the aim of this study was to evaluate compliance of checklist completion and its barrier for utilization at University of Gondar Hospital, Northwest Ethiopia. METHODS: A prospective observational study was conducted among 282 patients undergoing elective and emergency surgery from January to March 2013. Compliance and completeness rate with implementation of Sign-in, Time-out, and Sign-out domains was computed with SPSS 20 package. RESULTS: A total of 282 operations were performed and checklists were utilized in 39.7% (112/282) of cases. Among these, most checklists were employed during emergency procedures (61.6%) that need general anesthesia (75.9%) in department of surgery (58.9%). The overall compliance and completeness rate were 39.7 and 63.4% respectively. The sign-in, time-out and sign-out were missed in 30.5% (273/896), 35.4 % (436/1,232) and 45.7% (307/672) respectively. The main reasons cited for non-user were lack of previous training (45.1%) and lack of cooperation among surgical team members (21.6%). CONCLUSIONS AND RECOMMENDATIONS: The completeness rate was satisfactory but the overall compliance rate was suboptimal. An instrument that is used 40% of the time has been a fairly basic introduction without significant reinforcement training. Moreover, frequent use of the checklist during emergency cases has been deemed to be of value by clinicians. Supplementary training and attention to actual checklist use would be indicated to ensure that this valuable tool could be used more routinely and improve communication. Conducting regular audit of checklist utilization is also recommended. PMID- 26285825 TI - The content of social media's shared images about Ebola: a retrospective study. AB - OBJECTIVE: Social media have strongly influenced awareness and perceptions of public health emergencies, but a considerable amount of social media content is now carried through images, rather than just text. This study's objective is to explore how image-sharing platforms are used for information dissemination in public health emergencies. STUDY DESIGN: Retrospective review of images posted on two popular image-sharing platforms to characterize public discourse about Ebola. METHODS: Using the keyword '#ebola' we identified a 1% sample of images posted on Instagram and Flickr across two sequential weeks in November 2014. Images from both platforms were independently coded by two reviewers and characterized by themes. We reviewed 1217 images posted on Instagram and Flickr and identified themes. RESULTS: Nine distinct themes were identified. These included: images of health care workers and professionals [308 (25%)], West Africa [75 (6%)], the Ebola virus [59 (5%)], and artistic renderings of Ebola [64 (5%)]. Also identified were images with accompanying embedded text related to Ebola and associated: facts [68 (6%)], fears [40 (3%)], politics [46 (4%)], and jokes [284 (23%)]. Several [273 (22%)] images were unrelated to Ebola or its sequelae. Instagram images were primarily coded as jokes [255 (42%)] or unrelated [219 (36%)], while Flickr images primarily depicted health care workers and other professionals [281 (46%)] providing care or other services for prevention or treatment. CONCLUSION: Image sharing platforms are being used for information exchange about public health crises, like Ebola. Use differs by platform and discerning these differences can help inform future uses for health care professionals and researchers seeking to assess public fears and misinformation or provide targeted education/awareness interventions. PMID- 26285826 TI - Temporal patterns of physical activity and sedentary behavior in 10-14 year-old children on weekdays. AB - BACKGROUND: An important but often ignored aspect of physical activity (PA) and sedentary behavior (SB) is the chronological succession of activities, or temporal pattern. The main purposes of this study were (1) to investigate when certain types of PA and SB compete against each other during the course of the day and (2) compare intensity- and domain-specific activity levels during different day-segments. METHODS: The study sample consists of 211 children aged 10-14, recruited from 15 primary and 15 secondary schools. PA was assessed combining the SenseWear Mini Armband (SWM) with an electronic activity diary. The intensity- and domain-specific temporal patterns were plotted and PA differences between different day-segments (i.e., morning, school, early evening and late evening) were examined using repeated-measures ANCOVA models. RESULTS: Physical activity level (PAL) was highest during the early evening (2.51 METSWM) and school hours (2.49 METSWM); the late evening segment was significantly less active (2.21 METSWM) and showed the highest proportion of sedentary time (54 % of total time-use). Throughout the different day-segments, several domains of PA and SB competed with each other. During the critical early-evening segment, screentime (12 % of time-use) and homework (10 %) were dominant compared to activity domains of sports (4 %) and active leisure (3 %). The domain of active travel competed directly with motor travel during the morning (5 % and 6 % respectively) and early-evening segment (both 8 %). CONCLUSIONS: Throughout the day, different aspects of PA and SB go in competition with each other, especially during the time period immediately after school. Detailed information on the temporal patterns of PA and SB of children could help health professionals to develop more effective PA interventions and promotion strategies. By making adaptations to the typical day schedule of children (e.g., through the introduction of extra-curricular PA after school hours), their daily activity levels might improve. PMID- 26285827 TI - Hypoglycemic and hypolipidemic activities of aqueous extract of flowers from Nycantus arbor-tristis L. in male mice. AB - BACKGROUND: Boiled aqueous extract of flowers (AEF) from Nyctanthes arbor-tristis L. are used in Sri Lankan traditional Ayruvedic Medicine to manage diabetes mellitus. AEF has widely been used as a folk medicine for the treatment of various ailments due to its therapeutic activity. However, little is known concerning therapeutic activity of the extract as well as its underline mechanisms and safety. Diabetes is known to increase low-density cholesterol and decrease high-density cholesterol thus triggering coronary diseases. Hence, the primary objective of the present study is to investigate the hypoglycemic and hypolipidemic activities of the AEF. METHODS: AEF was prepared and male mice (n = 9 group) were gavaged either with 250, 500 and 750 mg/kg of AEF or distilled water (DW). Subsequently, fasting and random blood glucose concentrations were determined. To investigate mechanisms of actions of AEF, animals were orally administered with 500 mg/kg or the vehicle (DW) and glucose tolerance was performed before and after glucose challenge. For further studies, in vitro alpha amylase assay and glucose absorption from the gastrointestinal tract were performed using 500 mg/kg of the extract. Additionally, glycogen content in the liver and skeletal muscles, a complete lipid profile assay, and toxicological and biochemical parameters were conducted after a chronic study. RESULTS: Five hundred mg/kg and 750 mg/kg of AEF significantly (p < 0.01) reduced fasting blood glucose levels respectively by 49 and 39% at 4 h post-treatment, while 500 mg/kg of AEF also decreased the random blood glucose level significantly (p < 0.01) by 32% at 4 h post-treatment. AEF significantly inhibited glucose absorption by 85% from the intestine and increased diaphragm uptake of glucose by 64%. The extract also exhibited inhibition (16.66%) of alpha-amylase enzyme activity. It also decreased the level of total cholesterol (by 44.8%), triglyceride (by 53%) and increased (by 57%) the high-density lipoprotein cholesterol. Treatment with AEF did not induce any overt signs of toxicity or hepatotoxicity. CONCLUSION: Results the present study indicated that AEF possess hypoglycemic and hypolipdemic properties. Therefore, AEF could be used as an alternative medicine in management of diabetes mellitus. PMID- 26285828 TI - Elevation of serum S100 protein concentration as a marker of ischemic brain damage in extremely preterm infants. AB - BACKGROUND: Periventricular leukomalacia (PVL) is serious ischemic brain damage that occurs in extreme preterm infants. It is traditionally diagnosed by cranial echography. The purpose of this study was to investigate the relationship between serum S100 calcium-binding protein B (S100B) concentrations and ischemic brain damage, and to find the cutoff value for the early identification of ischemic brain damage in high-risk preterm infants. METHODS: At the age of 3 days, 7 days, 14 days, and 21 days, and before discharge, 22 extremely premature infants (i.e., gestational age <33 weeks) underwent blood sampling to determine the S100B concentrations and cranial echography examinations. The severity of ischemic brain damage in echographic images was scored on a scale of 0-11, and was recorded as the brain echography index (BEI). If the last BEI value was >=7, the enrolled infants were grouped in the brain damage group. RESULTS: Eight infants were assigned to the brain damage group and 14 infants were assigned to the no brain damage group. At each age point of the blood samplings, the serum S100B concentrations were significantly higher in the brain damage group than in the no brain damage group. There was a significantly positive correlation between the serum S100B concentrations and the BEI on the same day (r = 0.738, p < 0.001) and 7 days later (r = 0.774, p < 0.001). The receiver operating characteristic curve for the serum S100B concentrations showed that the area under curve was 0.985 (p < 0.001). The cutoff value of serum S100B of 1.0 MUg/L had a sensitivity of 93.8% and specificity of 90.5% for the diagnosis of ischemic brain damage. CONCLUSION: An elevation in the serum S100B concentration is highly associated with ischemic brain damage in extreme preterm infants. Ischemic brain damage in a high-risk preterm infant is strongly suggested if the early serum S100B concentration is > 1.0 MUg/L. PMID- 26285830 TI - Sleep spindle reductions in schizophrenia and its implications for the development of cortical body map. PMID- 26285829 TI - CX3CR1 is dysregulated in blood and brain from schizophrenia patients. AB - The molecular mechanisms underlying schizophrenia remain largely unknown. Although schizophrenia is a mental disorder, there is increasing evidence to indicate that inflammatory processes driven by diverse environmental factors play a significant role in its development. With gene expression studies having been conducted across a variety of sample types, e.g., blood and postmortem brain, it is possible to investigate convergent signatures that may reveal interactions between the immune and nervous systems in schizophrenia pathophysiology. We conducted two meta-analyses of schizophrenia microarray gene expression data (N=474) and non-psychiatric control (N=485) data from postmortem brain and blood. Then, we assessed whether significantly dysregulated genes in schizophrenia could be shared between blood and brain. To validate our findings, we selected a top gene candidate and analyzed its expression by RT-qPCR in a cohort of schizophrenia subjects stabilized by atypical antipsychotic monotherapy (N=29) and matched controls (N=31). Meta-analyses highlighted inflammation as the major biological process associated with schizophrenia and that the chemokine receptor CX3CR1 was significantly down-regulated in schizophrenia. This differential expression was also confirmed in our validation cohort. Given both the recent data demonstrating selective CX3CR1 expression in subsets of neuroimmune cells, as well as behavioral and neuropathological observations of CX3CR1 deficiency in mouse models, our results of reduced CX3CR1 expression adds further support for a role played by monocyte/microglia in the neurodevelopment of schizophrenia. PMID- 26285831 TI - Higher Prevalence of Left-Handedness in Twins? Not After Controlling Birth Time Confounders. AB - Pregnancy- and birth-related factors may have an effect on handedness. Compared with singletons, twins have a lower birth weight, shorter gestational age, and are at higher risk for birth complications. We tested whether the prevalence of left-handedness is higher among twins than singletons, and if so, whether that difference is fully explained by pregnancy and birth-related differences between twins and singletons. We analyzed Finnish population-based datasets; included were 8,786 twins and 5,892 singletons with information on birth weight (n = 12,381), Apgar scores (n = 11,129), and gestational age (n = 11,811). Two twin cohorts were involved: FinnTwin12 included twins born during 1983-1987, and FinnTwin16 included twins born during 1974-1979. We had two comparison groups of singletons: 4,101 individuals born during 1986-1988 and enrolled in the Helsinki Ultrasound Trial, and 1,791 individuals who were partners of FinnTwin16 twins. We used logistic regression models with writing hand as the outcome for comparison and evaluating effects of covariates. Left-handedness was more common in twins (9.67%) than in singletons (8.27%; p = .004). However, Apgar scores were associated with handedness, and after controlling for covariates, we found no difference in the prevalence of left-handedness between twins and singletons. Increased left-handedness among twins, often reported by others, was evident in our data, but only among our older twin cohorts, and that association disappeared after removing effects of perinatal covariates. PMID- 26285833 TI - CNVs in neurodevelopmental disorders. PMID- 26285832 TI - High dietary protein decreases fat deposition induced by high-fat and high sucrose diet in rats. AB - High-protein diets are known to reduce adiposity in the context of high carbohydrate and Western diets. However, few studies have investigated the specific high-protein effect on lipogenesis induced by a high-sucrose (HS) diet or fat deposition induced by high-fat feeding. We aimed to determine the effects of high protein intake on the development of fat deposition and partitioning in response to high-fat and/or HS feeding. A total of thirty adult male Wistar rats were assigned to one of the six dietary regimens with low and high protein, sucrose and fat contents for 5 weeks. Body weight (BW) and food intake were measured weekly. Oral glucose tolerance tests and meal tolerance tests were performed after 4th and 5th weeks of the regimen, respectively. At the end of the study, the rats were killed 2 h after ingestion of a calibrated meal. Blood, tissues and organs were collected for analysis of circulating metabolites and hormones, body composition and mRNA expression in the liver and adipose tissues. No changes were observed in cumulative energy intake and BW gain after 5 weeks of dietary treatment. However, high-protein diets reduced by 20 % the adiposity gain induced by HS and high-sucrose high-fat (HS-HF) diets. Gene expression and transcriptomic analysis suggested that high protein intake reduced liver capacity for lipogenesis by reducing mRNA expressions of fatty acid synthase (fasn), acetyl-CoA carboxylase a and b (Acaca and Acacb) and sterol regulatory element binding transcription factor 1c (Srebf-1c). Moreover, ketogenesis, as indicated by plasma beta-hydroxybutyrate levels, was higher in HS-HF-fed mice that were also fed high protein levels. Taken together, these results suggest that high protein diets may reduce adiposity by inhibiting lipogenesis and stimulating ketogenesis in the liver. PMID- 26285834 TI - USP8 mutation in Cushing's disease. PMID- 26285835 TI - Targeting interleukin-17 receptors. PMID- 26285836 TI - PlGF, immune system and hypertension. PMID- 26285837 TI - Efficacy of Spirulina platensis in improvement of the reproductive performance and easing teratogenicity in hyperglycemic albino mice. AB - OBJECTIVES: The present study evaluates the therapeutic efficacy of cell suspension of Spirulina platensis (SP) on estrous cycle, fetal development and embryopathy in alloxan (AXN) induced hyperglycemic mice. MATERIALS AND METHODS: Diabetes was induced by intra-peritoneal administration of AXN. Mice with blood glucose level above 200 mg/dl were divided into Group I (control), Group II (diabetic control), Group III (diabetic control mice fed with SP), and Group IV (control mice fed with SP). Litter counts, estrous cycles, percent survival of litter, and gestation length were recorded. RESULTS: In hyperglycemic mice, a significant (P < 0.05) increase in duration of diestrus (14.48%), estrus (84.21%), and metestrus (164.15%) with concomitant decrease in proestrus phase by 26.13% was recorded when compared with control. Reduction in litter count and survival of litter was 68.67% and 88.38%, respectively, whereas gestation length increased to 14.51% day in diabetic mice, but recovery in these parameters was observed (P < 0.05) when subjected to SP treatment. SP resulted in increased fertility rate from 77.5% to 82.5% and dropped off resorption of the fetus to 33.73% while the survival rate of offspring of diabetic mice went up to 88.89% from 83.61%. CONCLUSIONS: These findings suggest that SP is effective in improving the reproductive performance and easing teratogenic effects in diabetic mice and hence warrants further detailed dose-dependent studies to understand its mechanism of action. PMID- 26285838 TI - NMR-Based Metabolomic Analysis of Huanglongbing-Asymptomatic and -Symptomatic Citrus Trees. AB - Huanglongbing (HLB) is one of the most severe diseases that affects citrus trees worldwide and is associated with the yet uncultured bacteria Candidatus Liberibacter spp. To assess the metabolomic differences between HLB-asymptomatic and -symptomatic tissues, extracts from leaf and root samples taken from a uniform 6-year-old commercial orchard of Valencia trees were subjected to nuclear magnetic resonance (NMR) and chemometrics. The results show that the symptomatic trees had higher sucrose content in their leaves and no variation in their roots. In addition, proline betaine and malate were detected in smaller amounts in the HLB-affected symptomatic leaves. The changes in metabolic processes of the plant in response to HLB are corroborated by the relationship between the bacterial levels and the metabolic profiles. PMID- 26285839 TI - Hydrocarbon on Carbon: Coherent Vibrational Spectroscopy of Toluene on Graphite. AB - The ability to study the interactions of hydrocarbons on carbon surfaces is an integral step toward gaining a molecular level understanding of the chemical reactions and physical properties occurring on them. Here, we apply vibrational sum frequency generation (SFG) to determine the tilt angle of toluene, a common organic solvent, on millimeter-thick highly oriented pyrolytic graphite (HOPG). The combination of a time-delay technique, which results in the successful suppression of the nonresonant SFG response, and a null angle method is shown to overcome the "strong optical absorber" problem posed by macroscopically thick carbon samples and yields a molecular tilt angle of toluene in the range of 37 degrees to 42 degrees from the surface normal. The implications of this approach for determining the orientation of organic species adsorbed on carbon interfaces, which are important for energy-relevant processes, are discussed. PMID- 26285840 TI - Ethanol Diffusion on Rutile TiO2(110) Mediated by H Adatoms. AB - We have studied the diffusion of ethanol on rutile TiO2(110)-(1 * 1) by high resolution scanning tunneling microscopy (STM) measurements and density functional theory (DFT) calculations. Time-lapsed STM images recorded at ~200 K revealed the diffusion of ethanol molecules both parallel and perpendicular to the rows of surface Ti atoms. The diffusion of ethanol molecules perpendicular to the rows of surface Ti atoms was found to be mediated by H adatoms in the rows of bridge-bonded O (Obr) atoms similarly to previous results obtained for water monomers. In contrast, the diffusion of H adatoms across the Ti rows, mediated by ethanol molecules, was observed only very rarely and exclusively on fully hydrogenated TiO2(110) surfaces. Possible reasons why the diffusion of H adatoms across the Ti rows mediated by ethanol molecules occurs less frequently than the cross-row diffusion of ethanol molecules mediated by H adatoms are discussed. PMID- 26285841 TI - Insufficient Hartree-Fock Exchange in Hybrid DFT Functionals Produces Bent Alkynyl Radical Structures. AB - Density functional theory (DFT) is often used to determine the electronic and geometric structures of molecules. While studying alkynyl radicals, we discovered that DFT exchange-correlation (XC) functionals containing less than ~22% Hartree Fock (HF) exchange led to qualitatively different structures than those predicted from ab initio HF and post-HF calculations or DFT XCs containing 25% or more HF exchange. We attribute this discrepancy to rehybridization at the radical center due to electron delocalization across the triple bonds of the alkynyl groups, which itself is an artifact of self-interaction and delocalization errors. Inclusion of sufficient exact exchange reduces these errors and suppresses this erroneous delocalization; we find that a threshold amount is needed for accurate structure determinations. Below this threshold, significant errors in predicted alkyne thermochemistry emerge as a consequence. PMID- 26285842 TI - Stability of Positively Charged Solutes in Water: A Transition from Hydrophobic to Hydrophilic. AB - To improve the description of solvation thermodynamics of biomolecules, we report here the dependence of solvation on the curvature and surface charge of positively charged solutes in water based on extensive molecular dynamics simulations analyzed using the two-phase thermodynamic method. At a surface charge of +0.4e, the compensating forces of favorable electrostatic stabilization and entropic destabilization cancel almost exactly, representing a molecular crossover point from hydrophobic to hydrophilic behavior, independent of curvature. These results suggest that one should include charge-dependent entropic corrections to continuum models aimed at predicting the solvation free energies of large biomolecules. PMID- 26285843 TI - Probing the Low-Lying Electronic States of Cyclobutanetetraone (C4O4) and Its Radical Anion: A Low-Temperature Anion Photoelectron Spectroscopic Approach. AB - Despite a seemingly simple appearance, cyclobutanetetraone (C4O4) has four low lying electronic states. Determining the energetic ordering of these states and the ground state of C4O4(-) theoretically has been proven to be considerably challenging and remains largely unresolved to date. Here, we report a low temperature negative ion photoelectron spectroscopic approach. Well-resolved spectra were obtained at both 193 and 266 nm. Combined with recent theoretical studies and our own Franck-Condon factors simulations, the ground state of C4O4( ) and the ground and two low-lying excited states of C4O4 are determined to be (2)A2u, (3)B2u, (1)A1g (8pi), and (1)B2u, respectively. The frequency of the ring breathing mode (1810 +/- 20 cm(-1)), the electron affinity (3.475 +/- 0.005 eV), and the term values of (1)A1g (8pi) (6.27 +/- 0.5 kJ/mol) and (1)B2u (13.50 +/- 0.5 kJ/mol) are also directly obtained from the experiments. PMID- 26285844 TI - High Capacity MoO2/Graphite Oxide Composite Anode for Lithium-Ion Batteries. AB - Nanostructured MoO2/graphite oxide (GO) composites are synthesized by a simple solvothermal method. X-ray diffraction and transmission electron microscopy analyses show that with the addition of GO and the increase in GO content in the precursor solutions, MoO3 rods change to MoO2 nanorods and then further to MoO2 nanoparticles, and the nanorods or nanoparticles are uniformly distributed on the surface of the GO sheets in the composites. The MoO2/GO composite with 10 wt % GO exhibits a reversible capacity of 720 mAh/g at a current density of 100 mA/g and 560 mAh/g at a high current density of 800 mA/g after 30 cycles. The improved reversible capacity, rate capacity, and cycling performance of the composites are attributed to synergistic reaction between MoO2 and GO. PMID- 26285845 TI - Polyoxometalate Surfactants as Unique Molecules for Interfacial Self-Assembly. AB - Whereas, commonly, Langmuir monolayers are structurally dominated by the aliphatic chains, we present here the first case of monolayers where the chains merely serve anchoring at the air/water interface and the organization is dictated by the hydrophilic head group self-assembling in a hexagonal lattice. These head groups are polyoxometalates known for their multifunctional potential. The chain length has been systematically varied, allowing for a general study of the impact of the chain length on the supramolecular structure. These model structures are studied here by a combination of modern techniques, the leading ones being X-ray reflectivity and grazing incidence X-ray diffraction. The quantitative structural insights offered in this Letter might represent a starting point for the rational design and study of a new class of emulsions, including an organic tail and a multifunctional inorganic polar head. PMID- 26285846 TI - The Molecular Volcano Revisited: Determination of Crack Propagation and Distribution During the Crystallization of Nanoscale Amorphous Solid Water Films. AB - Temperature programmed desorption (TPD) is utilized to determine the length distribution of cracks formed through amorphous solid water (ASW) during crystallization. This distribution is determined by monitoring how the thickness of an ASW overlayer alters desorption of an underlayer of O2. As deposited, ASW prevents desorption of O2. During crystallization, cracks form through the ASW and open a path to vacuum, which allows O2 to escape in a rapid episodic release known as the "molecular volcano". Sufficiently thick ASW overlayers further trap O2 resulting in a second, higher temperature, O2 desorption peak. The evolution of this trapping peak with overlayer thickness is the basis for determining the length distribution of crystallization-induced cracks spanning the ASW. Reflection absorption infrared spectroscopy (RAIRS) and TPD of multicomponent parfait structures of ASW, O2, and Kr indicate that a preponderance of these cracks propagate down from the outer surface of the ASW. PMID- 26285847 TI - Control of Plasmonic Superradiance in Metallic Nanoparticle Assembly by Light Induced Force and Fluctuations. AB - The possibility of simultaneous control of the configuration and optical functions of a metallic nanoparticle (NP) assembly by light-induced force (LIF) and thermal fluctuations has been demonstrated on the basis of self-consistent theory of LIF and nonequilibrium dynamics. It has been clarified that the NPs are arranged parallel to the polarization of the focused laser beam under the balance of LIF and the electrostatic repulsive force due to the ions on the surface of NPs. Particularly, in such a NP assembly consisting of high-density NPs, the light-scattering rate (radiative decay) of localized surface plasmon polaritons (LSPPs) can be drastically enhanced to be greater than 100 meV (10 times that of single NPs), and the spectral width is also greatly broadened due to the superradiance effect. The results will provide a foundation of the principles for designing a NP assembly with controllable light scattering for highly efficient broad-band light energy conversion devices. PMID- 26285848 TI - Transient H2O Infrared Satellite Peaks Produced in UV Irradiated Formic Acid Doped Solid Parahydrogen. AB - We report newly identified satellite features of the R(0) rovibrational transition of all the fundamental modes of HDO and the nu3 mode of H2O measured via FTIR spectroscopy immediately after the 193 nm in situ photolysis of formic acid (HCOOH and DCOOD) in solid parahydrogen. The intensities of these satellite features decay slowly with a time constant of tau = 121(7) min after photolysis, even when the sample is maintained below 2 K. We propose that the van der Waals complex H...H2O (H...HDO) is the carrier of the satellite peaks and that these metastable complexes are produced after the low-temperature tunneling reaction of the OH (OD) photoproduct with the parahydrogen host. PMID- 26285849 TI - Direct Observation of Hydrogen Tunneling Dynamics in Photoexcited Phenol. AB - The excited-state dynamics of phenol following ultraviolet (UV) irradiation have received considerable interest in recent years, most notably because they can provide a model for understanding the UV-induced dynamics of the aromatic amino acid tyrosine. Despite this, there has been some debate as to whether hydrogen tunneling dynamics play a significant role in phenol's excited-state O-H bond fission when UV excitation occurs below the (1)pipi*/(1)pisigma* conical intersection (CI). In this Letter, we present direct evidence that (1)pisigma* mediated O-H bond fission below the (1)pipi*/(1)pisigma* CI proceeds exclusively through hydrogen tunneling dynamics. The observation of hydrogen tunneling may have some parallels with proton tunneling dynamics from tyrosine residues (along the O-H bond of the phenol moiety) in a wide range of natural enzymes, potentially adding further justification for utilizing phenols as model systems for investigating tyrosine-based dynamics. PMID- 26285850 TI - Nanodroplet Transport on Vibrated Nanotubes. AB - We show by molecular dynamics simulations that water nanodroplets can be transported along and around the surfaces of vibrated carbon nanotubes. In our simulations, a nanodroplet with a diameter of ~4 nm is adsorbed on a (10,0) single-wall carbon nanotube, which is vibrated at one end with a frequency of 208 GHz and an amplitude of 1.2 nm. The generated linearly polarized transverse acoustic waves pass linear momentum to the nanodroplet, which becomes transported along the nanotube with a velocity of ~30 nm/ns. When circularly polarized waves are passed along the nanotubes, the nanodroplets rotate around them and eventually become ejected from their surfaces when their angular velocity is ~50 rad/ns. PMID- 26285851 TI - Development of Pharmaceutically Adapted Mesoporous Silica Nanoparticles Platform. PMID- 26285852 TI - Universal Correction of Density Functional Theory to Include London Dispersion (up to Lr, Element 103). AB - Conventional density functional theory (DFT) fails to describe accurately the London dispersion essential for describing molecular interactions in soft matter (biological systems, polymers, nucleic acids) and molecular crystals. This has led to several methods in which atom-dependent potentials are added into the Kohn Sham DFT energy. Some of these corrections were fitted to accurate quantum mechanical results, but it will be tedious to determine the appropriate parameters to describe all of the atoms of the periodic table. We propose an alternative approach in which a single parameter in the low-gradient (lg) functional form is combined with the rule-based UFF (universal force-field) nonbond parameters developed for the entire periodic table (up to Lr, Z = 103), named as a DFT-ulg method. We show that DFT-ulg method leads to a very accurate description of the properties for molecular complexes and molecular crystals, providing the means for predicting more accurate weak interactions across the periodic table. PMID- 26285853 TI - Critical Considerations in the Biomedical Use of Mesoporous Silica Nanoparticles. AB - Since the first report of mesoporous silica nanoparticles in 2001, many efforts have been made to develop them for biomedical applications. With the emergence of new designs and increasingly complex synthetic schemes, mesoporous silica nanoparticles have never been more promising. For this promise to be fulfilled, however, practical considerations for biomedical use must be carefully addressed. Many current mesoporous silica reports, even those reporting in vivo work, neglect the observation of nanoparticle size, pore structure, aggregation state, and biodegradability under biological conditions before administration. These critical considerations, beginning at synthetic stages, must be taken into account to make effective and safe mesoporous silica nanoparticles for biomedical use and timely application in clinical trials. Herein, we present a comprehensive review of mesoporous silica nanoparticle synthetic strategies, pointing out nanoparticle behavior under biological conditions and how it may affect in vitro and in vivo results. PMID- 26285854 TI - RI-MP2 Gradient Calculation of Large Molecules Using the Fragment Molecular Orbital Method. AB - The second-order Moller-Plesset perturbation theory (MP2) gradient using resolution of the identity approximation (RI-MP2 gradient) was combined with the fragment molecular orbital (FMO) method to evaluate the gradient including electron correlation for large molecules. In this study, we adopted a direct implementation of the RI-MP2 gradient, in which a characteristic feature of the FMO scheme was utilized. Test calculations with a small peptide presented a computational advantage of the RI-MP2 gradient over the canonical MP2 gradient. In addition, it was shown that the error of the RI-MP2 gradient, caused by RI approximation, was negligible. As an illustrative example, we performed gradient calculations for two biomolecules-a prion protein with GN8 and a human immunodeficiency virus type 1 (HIV1) protease with lopinavir (LPV). These calculations demonstrated that the gradient including the correlation effect could be evaluated with only about twice the computational effort of the Hartree Fock (HF) gradient. PMID- 26285855 TI - Apparent Decoupling of the Dynamics of a Protein from the Dynamics of its Aqueous Solvent. AB - Studies of the low-temperature dynamics of proteins in aqueous solutions are limited by the crystallization of water. In this work, we use a solution of LiCl in D2O as a solvent for a protein to prevent crystallization and study the dynamics of both the protein and its aqueous solvent by quasielastic neutron scattering (QENS) in the temperature range of 210 to 290 K. Our results reveal that, while the dynamics of the aqueous solvent undergoes a crossover at about 220 K, the dynamics of the protein itself shows no transition at this temperature. The prevailing view is that the beta-fluctuations of the protein are governed by the alpha-fluctuations of the solvent; therefore, observation of the apparent decoupling between the dynamics of the protein and its solvent below the crossover temperature is remarkable. PMID- 26285856 TI - How Important is Working with an Ordered Electrode to Improve the Charge Collection Efficiency in Nanostructured Solar Cells? AB - The collection efficiency of carriers in solar cells based on nanostructured electrodes is determined for different degrees or morphological one-dimensional order. The transport process is modeled by random walk numerical simulation in a mesoporous electrode that resembles the morphology of nanostructured TiO2 electrodes typically used in dye-sensitized solar cells and related systems. By applying an energy relaxation procedure in the presence of an external potential, a preferential direction is induced in the system. It is found that the partially ordered electrode can almost double the collection efficiency with respect to the disordered electrode. However, this improvement depends strongly on the probability of recombination. For too rapid or too slow recombination, working with partially ordered electrodes will not be beneficial. The computational method utilized here makes it possible to relate the charge collection efficiency with morphology. The collection efficiency is found to reach very rapidly a saturation value, meaning that, in the region of interest, a slight degree of ordering might be sufficient to induce a large improvement in collection efficiency. PMID- 26285857 TI - Enhancement of Near-IR Photoelectric Conversion in Dye-Sensitized Solar Cells Using an Osmium Sensitizer with Strong Spin-Forbidden Transition. AB - A new osmium (Os) complex of the [Os(tcterpy)-(4,4'-bis(p-butoxystyryl)-2,2' bipyridine)Cl]PF6 (Os-stbpy) has been synthesized and characterized for dye sensitized solar cells (DSSCs). The Os-stbpy dye shows enhanced spin-forbidden absorptions around 900 nm. The DSSCs with Os-stbpy show a wide-band spectral response up to 1100 nm with high overall conversion efficiency of 6.1% under standard solar illumination. PMID- 26285858 TI - Synthesis and Activities of Rutile IrO2 and RuO2 Nanoparticles for Oxygen Evolution in Acid and Alkaline Solutions. AB - The activities of the oxygen evolution reaction (OER) on iridium-oxide- and ruthenium-oxide-based catalysts are among the highest known to date. However, the OER activities of thermodynamically stable rutile iridium oxide (r-IrO2) and rutile iridium oxide (r-RuO2), normalized to catalyst mass or true surface area are not well-defined. Here we report a synthesis of r-IrO2 and r-RuO2 nanoparticles (NPs) of ~6 nm, and examine their OER activities in acid and alkaline solutions. Both r-IrO2 and r-RuO2 NPs were highly active for OER, with r RuO2 exhibiting up to 10 A/goxide at 1.48 V versus reversible hydrogen electrode. When comparing the two, r-RuO2 NPs were found to have slightly higher intrinsic and mass OER activities than r-IrO2 in both acid and basic solutions. Interestingly, these oxide NPs showed higher stability under OER conditions than commercial Ru/C and Ir/C catalysts. Our study shows that these r-RuO2 and r-IrO2 NPs can serve as a benchmark in the development of active OER catalysts for electrolyzers, metal-air batteries, and photoelectrochemical water splitting applications. PMID- 26285859 TI - Nanotechnology Meets Biology: Peptide-based Methods for the Fabrication of Functional Materials. AB - Nature exploits sustainable methods for the creation of inorganic materials on the nanoscale for a variety of applications. To achieve such capabilities, biomolecules such as peptides and proteins have been developed that recognize and bind the different compositions of materials. While a diverse set of materials binding sequences are present in the biosphere, biocombinatorial techniques have been used to rapidly identify peptides that facilitate the formation of new materials of technological importance. Interestingly, the binding motif of the peptides at the inorganic surface is likely to control the size, structure, composition, shape, and functionality of the final materials. In order to advance these intriguing new biomimetic approaches, a complete understanding of this biotic/abiotic interface is required. In this Perspective, we highlight recent advances in the biofunctionalization of nanoparticles with potential applications ranging from catalysis and energy storage to plasmonics and biosensing. We specifically focus on the physical characterization of the peptide-based surface from which specificity and activity are likely embedded. PMID- 26285860 TI - On the Origin of the Energy Gain in Epitaxial Growth of Molecular Films. AB - The material properties of organic thin films depend strongly on their order. The different types of epitaxy may complicate the exploration of the large variety of ordered systems and its exploitation in potential electronic devices. In this Letter, we develop a coherent description of the driving force that creates epitaxial systems. We focus on flat-lying organic adsorbates and explain the energy gain in commensurate, point-on-line, and line-on-line epitaxy. We use potential energy maps to visualize our concept and to derive a relation that allows anticipating epitaxial growth from low-energy electron diffraction (LEED) data. A unified description facilitates the identification and interpretation of experimentally observed adsorbate structures, whereas the rationalized expectation from LEED means a considerable speed gain if suitable candidates for organic-organic epitaxy are searched for in a combinatory approach. PMID- 26285861 TI - Surface-Selective Solution NMR Studies of Functionalized Zeolite Nanoparticles. AB - The surface chemistry of zeolite nanoparticles functionalized with the organosilane aminopropyldimethylmethoxysilane (APDMMS) was selectively probed using solution (1)H NMR spectroscopy. The use of solution NMR spectroscopy results in high-resolution NMR spectra, and the technique is selective for protons on the surface organic functional groups due to their motional averaging in solution. In this study, (1)H solution NMR spectroscopy was used to investigate the interface of the organic functional groups of APDMMS functionalized silicalite nanoparticles (~35 nm) in D2O. The pKa for the amine group of APDMMS-functionalized silicalite nanoparticles in D2O was determined using an NMR-pH titration method based on the variation in the proton chemical shift for the alkyl group protons closest to the amine group with pH. The resulting NMR spectra demonstrate the sensitivity of solution NMR spectroscopy to the electronic environment and structure of the surface functional groups. PMID- 26285862 TI - Physicochemical Profiling of Surfactant-Induced Membrane Dynamics in a Cell-Sized Liposome. AB - We used a cell-sized model system, giant liposomes, to investigate the interaction between lipid membranes and surfactants, and the membrane transformation during the solubilization process was captured in real time. We found that there are four distinct dynamics in surfactant-induced membrane deformation: an episodic increase in the membrane area prior to pore-forming associated shrinkage (Dynamics A), fission into many small liposomes (Dynamics B), the formation of multilamellar vesicles and peeling (Dynamics C), and bursting (Dynamics D). Classification of the diversity of membrane dynamics may contribute to a better understanding of the physicochemical mechanism of membrane solubilization induced by various surfactants. PMID- 26285863 TI - Orbital-Symmetry-Dependent Electron Transfer through Molecules Assembled on Metal Substrates. AB - Femtosecond charge-transfer dynamics in self-assembled monolayers of cyano terminated ethane-thiolate on gold substrates was investigated with the core hole clock method. By exploiting symmetry selection rules rather than energetic selection, electrons from the nitrogen K-shell are state-selectively excited into the two symmetry-split pi* orbitals of the cyano end group with X-ray photons of well-defined polarization. The charge-transfer times from these temporarily occupied orbitals to the metal substrate differ significantly. Theoretical calculations show that these two pi* orbitals extend differently onto the alkane backbone and the anchoring sulfur atom, thus causing the observed dependence of the electron-transfer dynamics on the symmetry of the orbital. PMID- 26285864 TI - Diffusion Coefficients from (13)C PGSE NMR Measurements-Fluorine-Free Ionic Liquids with the DCTA(-) Anion. AB - Pulsed-field gradient spin-echo (PGSE) NMR is a widely used method for the determination of molecular and ionic self-diffusion coefficients. The analysis has thus far been limited largely to (1)H, (7)Li, (19)F, and (31)P nuclei. This limitation handicaps the analysis of materials without these nuclei or for which these nuclei are insufficient for complete characterization. This is demonstrated with a class of ionic liquids (or ILs) based on the nonfluorinated anion 4,5 dicarbonitrile-1,2,3-triazole (DCTA(-)). It is demonstrated here that (13)C-PGSE NMR can be used to both verify the diffusion coefficients obtained from other nuclei, as well as characterize materials that lack commonly scrutinized nuclei - all without the need for specialized NMR methods. PMID- 26285865 TI - Small-Angle X-ray Scattering Investigations of Biomolecular Confinement, Loading, and Release from Liquid-Crystalline Nanochannel Assemblies. AB - This Perspective explores the recent progress made by means of small-angle scattering methods in structural studies of phase transitions in amphiphilic liquid-crystalline systems with nanochannel architectures and outlines some future directions in the area of hierarchically organized and stimuli-responsive nanochanneled assemblies involving biomolecules. Time-resolved small-angle X-ray scattering investigations using synchrotron radiation enable monitoring of the structural dynamics, the modulation of the nanochannel hydration, as well as the key changes in the soft matter liquid-crystalline organization upon stimuli induced phase transitions. They permit establishing of the inner nanostructure transformation kinetics and determination of the precise sizes of the hydrophobic membraneous compartments and the aqueous channel diameters in self-assembled network architectures. Time-resolved structural studies accelerate novel biomedical, pharmaceutical, and nanotechnology applications of nanochannel soft materials by providing better control of DNA, peptide and protein nanoconfinement, and release from diverse stimuli-responsive nanocarrier systems. PMID- 26285866 TI - Complete APTX deletion in a patient with ataxia with oculomotor apraxia type 1. AB - BACKGROUND: Ataxia with oculomotor apraxia type 1 is an autosomal-recessive neurodegenerative disorder characterized by a childhood onset of slowly progressive cerebellar ataxia, followed by oculomotor apraxia and a severe primary motor peripheral axonal motor neuropathy. Ataxia with oculomotor apraxia type 1 is caused by bi-allelic mutations in APTX (chromosome 9p21.1). CASE PRESENTATION: Our patient has a clinical presentation that is typical for ataxia with oculomotor apraxia type 1 with no particularly severe phenotype. Multiplex Ligation-dependent Probe Amplification analysis resulted in the identification of a homozygous deletion of all coding APTX exons (3 to 9). SNP array analysis using the Illumina Infinium CytoSNP-850 K microarray indicated that the deletion was about 62 kb. Based on the SNP array results, the breakpoints were found using direct sequence analysis: c.-5 + 1225_*44991del67512, p.0?. Both parents were heterozygous for the deletion. Homozygous complete APTX deletions have been described in literature for two other patients. We obtained a sample from one of these two patients and characterized the deletion (156 kb) as c. 23729_*115366del155489, p.0?, including the non-coding exons 1A and 2 of APTX. The more severe phenotype reported for this patient is not observed in our patient. It remains unclear whether the larger size of the deletion (156 kb vs 62 kb) plays a role in the phenotype (no extra genes are deleted). CONCLUSION: Here we described an ataxia with oculomotor apraxia type 1 patient who has a homozygous deletion of the complete coding region of APTX. In contrast to the patient with the large deletion, our patient does not have a severe phenotype. More patients with deletions of APTX are required to investigate a genotype phenotype effect. PMID- 26285867 TI - Colorimetric and fluorimetric detection of fluoride and cyanide ions using tri and tetra coordinated boron containing chromophores. AB - Two organoboron based fluorophores pyrazabole and BODIPY have been designed and synthesized by the Pd-catalyzed Sonogashira cross-coupling reaction and successfully employed for fluoride and cyanide ion sensing. Pyrazabole acts as a fluorimetric sensor, whereas BODIPY acts as a fluorimetric as well as colorimetric sensor for fluoride and cyanide ions with ratiometric response. The photophysical properties of pyrazabole and BODIPY exhibit good electronic communication between triarylborane and pyrazabole/BODIPY. The single crystal X ray structure of the pyrazabole shows a chair conformation for the pyrazabole core. The packing in pyrazabole and BODIPY shows interesting supramolecular structures. The computational studies show good agreement with the experimental results. PMID- 26285868 TI - A long-life lithium ion sulfur battery exploiting high performance electrodes. AB - A novel lithium ion sulfur battery is formed by coupling an activated ordered mesoporous carbon-sulfur (AOMC-S) cathode and a nanostructured tin-carbon anode. The lithium ion cell has improved reversibility, high energy content and excellent cycle life. PMID- 26285870 TI - Involving patients in enrolment decisions for acute myocardial infarction trials. PMID- 26285869 TI - Characterization of nitrogen mustard formamidopyrimidine adduct formation of bis(2-chloroethyl)ethylamine with calf thymus DNA and a human mammary cancer cell line. AB - A robust, quantitative ultraperformance liquid chromatography ion trap multistage scanning mass spectrometric (UPLC/MS(3)) method was established to characterize and measure five guanine adducts formed by reaction of the chemotherapeutic nitrogen mustard (NM) bis(2-chloroethyl)ethylamine with calf thymus (CT) DNA. In addition to the known N7-guanine (NM-G) adduct and its cross-link (G-NM-G), the ring-opened formamidopyrimidine (FapyG) monoadduct (NM-FapyG) and cross-links in which one (FapyG-NM-G) or both (FapyG-NM-FapyG) guanines underwent ring-opening to FapyG units were identified. Authentic standards of all adducts were synthesized and characterized by NMR and mass spectrometry. These adducts were quantified in CT DNA treated with NM (1 MUM) as their deglycosylated bases. A two stage neutral thermal hydrolysis was developed to mitigate the artifactual formation of ring-opened FapyG adducts involving hydrolysis of the cationic adduct at 37 degrees C, followed by hydrolysis of the FapyG adducts at 95 degrees C. The limit of quantification values ranged between 0.3 and 1.6 adducts per 10(7) DNA bases when the equivalent of 5 MUg of DNA hydrolysate was assayed on column. The principal adduct formed was the G-NM-G cross-link, followed by the NM-G monoadduct; the FapyG-NM-G cross-link adduct; and the FapyG-NM-FapyG was below the limit of detection. The NM-FapyG adducts were formed in CT DNA at a level ~20% that of the NM-G adduct. NM-FapyG has not been previously quanitified, and the FapyG-NM-G and FapyG-NM-FapyG adducts have not been previously characterized. Our validated analytical method was then applied to measure DNA adduct formation in the MDA-MB-231 mammary tumor cell line exposed to NM (100 MUM) for 24 h. The major adduct formed was NM-G (970 adducts per 10(7) bases), followed by G-NM-G (240 adducts per 10(7) bases), NM-FapyG (180 adducts per 10(7) bases), and, last, the FapyG-NM-G cross-link adduct (6.0 adducts per 10(7) bases). These lesions are expected to contribute to NM-mediated toxicity and genotoxicity in vivo. PMID- 26285871 TI - Parenting Behaviors and Nutrition in Children with Leukemia. AB - The aim of this study was to examine whether parenting behaviors are associated with child nutrition amongst pre-school children receiving treatment for acute lymphoblastic leukemia (ALL), and to determine whether this association differs from that observed amongst a healthy population. Participants were 73 parents of children aged 2-6 years. The children were either a) receiving treatment for ALL (n = 43), or b) had no major medical history (n = 30). Participants completed psychometrically validated questionnaires that assessed parenting behaviors and child diet. Increased parental overprotection was associated with higher fruit and vegetable consumption for the control group but lower fruit and vegetable consumption for the ALL group. Parental overprotection, inconsistent discipline and emotional feeding were positively associated with non-core ("junk") food consumption for the ALL group, particularly those who had recently received steroid treatment. To the best of our knowledge, this is the first study to show that certain parenting behaviors may be associated with poor nutrition during treatment for ALL. In light of these results, parenting interventions, specifically targeting parenting behaviors such as assertive discipline, may be a mechanism for nutrition promotion amongst this vulnerable group. PMID- 26285872 TI - Taxing sugar should be just one element of a multifaceted campaign. PMID- 26285874 TI - Protein Arginylation: Over 50 Years of Discovery. AB - Posttranslational modifications have emerged in recent years as the major biological regulators responsible for the orders of magnitude increase in complexity of protein functions. These "molecular switches" affect nearly every protein in vivo by modulating their protein structure, activity, molecular interactions, and homeostasis. While over 350 protein modifications have been described, only a handful of them have been characterized. Until recently, protein arginylation has belonged to the list of obscure, poorly understood posttranslational modifications, before the recent explosion of studies has put arginylation on the map of intracellular metabolic pathways and biological processes. This chapter contains an overview of all the major milestones in the protein arginylation field, from its original discovery in 1963 to this day. PMID- 26285873 TI - The kynurenine pathway activities in a sub-Saharan HIV/AIDS population. AB - BACKGROUND: Tryptophan is an essential amino acid for the synthesis of proteins and important metabolites such as serotonin, melatonin, tryptamine and niacin. After protein synthesis, more than 90 % of tryptophan catabolism occurs along the kynurenine pathway. The inflammation-inducible enzyme indoleamine 2,3 dioxygenase (IDO) is responsible for the first rate-limiting step in the kynurenine pathway, i.e., oxidation of tryptophan to kynurenine. Excessive IDO activity in conditions such as HIV/AIDS may lead to tryptophan depletion and accumulation of metabolites downstream from kynurenine. Little is known about the kynurenine pathway of HIV/AIDS patients in sub-Saharan regions. This study, in a low income sub-Saharan HIV/AIDS population, examined the effects of activities in the kynurenine pathway on plasma levels of tryptophan, kynurenine and the neurotoxin quinolinic acid, and on de novo synthesis of nicotinamide. METHODS: Plasma samples were obtained from a cohort of 105 HIV patients and 60 controls. Kynurenine pathway metabolites were analysed using gas chromatography - mass spectrometry. ELISA and flow cytometry were used to assess plasma inflammatory markers. RESULTS: IDO activity, depletion of tryptophan, as well as accumulation of kynurenine and the neurotoxin quinolinic acid, were not only significantly greater in the patients than in the controls, but also markedly greater than in HIV/AIDS patients from developed countries. Tryptophan levels were 12.3 % higher, kynurenine levels 16.2 % lower, quinolinic acid levels 43.2 % lower and nicotinamide levels 27,2 % lower in patients on antiretroviral treatment than in antiretroviral-naive patients. Patients' kynurenine pathway metabolites correlated with the levels of inflammatory markers, including that of the major IDO-inducer, interferon-gamma. Indications are that the rate of de novo synthesis of nicotinamide in the kynurenine pathway correlates with increases in quinolinic acid levels up to a point where saturation of the enzyme quinolinate phosphoribosyl transferase occurs. CONCLUSIONS: Higher levels of inflammatory activity in this low income sub-Saharan HIV/AIDS population than in patients from developed countries lead to greater tryptophan depletion and greater accumulation of metabolites downstream from tryptophan with quinolinic acid levels often reaching levels associated with the development of HIV/AIDS-associated neurocognitive dysfunction. De novo synthesis of nicotinamide from quinolinic acid contributes to the maintenance of nicotinamide, and by implication NAD levels, in HIV/AIDS patients from low income populations. Antiretroviral treatment partially corrects disturbances in the kynurenine pathway. PMID- 26285875 TI - Recollection of How We Came Across the Protein Modification with Amino Acids by Aminoacyl tRNA-Protein Transferase. AB - Protein arginylation has been discovered in 1963 as a soluble activity in cell extracts that mediates addition of amino acids to proteins. This discovery was nearly accidental, but due to the persistence of the research team, it has been followed through and led to the emergence of a new field of research. This chapter describes the original discovery of arginylation and the first methods used to demonstrate the existence of this important biological process. PMID- 26285876 TI - Arginyltransferase: A Personal and Historical Perspective. AB - In the late 1960s and early 1970s, characterization of arginylation has been spearheaded via biochemical studies that enabled the first characterization of ATE1 and its substrate specificity. This essay summarized the recollections and insights from the era of research that followed from the original discovery of arginylation and led up to the identification of the arginylation enzyme. PMID- 26285877 TI - Arginylation in a Partially Purified Fraction of 150k * g Supernatants of Axoplasm and Injured Vertebrate Nerves. AB - Transfer RNA-mediated posttranslational protein modification by arginine has been demonstrated in vitro in axoplasm extruded from the giant axons of squid and in injured and regenerating vertebrate nerves. In nerve and axoplasm, the highest activity is found in a fraction of a 150,000 * g supernatant containing high molecular weight protein/RNA complexes but lacking molecules of <5 kDa. Arginylation (and protein modification by other amino acids) is not found in more purified, reconstituted fractions. The data are interpreted as indicating that it is critical to recover the reaction components in high molecular weight protein/RNA complexes in order to maintain maximum physiological activity. The level of arginylation is greatest in injured and growing vertebrate nerves compared with intact nerves, suggesting a role for these reactions in nerve injury/repair and during axonal growth. PMID- 26285878 TI - Preparation of ATE1 Enzyme from Native Mammalian Tissues. AB - Early studies of protein arginylation preceded the wide use of recombinant protein expression and relied heavily on fractionation of proteins from native tissues. The procedure described below has been developed in 1970 by R. Soffer, in the wake of arginylation discovery in 1963. This chapter follows the detailed procedure originally published by R. Soffer in the 1970, adapted from his article in consultation with R. Soffer, H. Kaji, and A. Kaji. PMID- 26285879 TI - Correlated Measurement of Endogenous ATE1 Activity on Native Acceptor Proteins in Tissues and Cultured Cells to Detect Cellular Aging. AB - Following our early discovery of arginylation in 1963, we have performed several studies to correlate its activity with essential biological processes. We employed cell- and tissue-based assays to detect both the level of acceptor proteins and the level of ATE1 activity under different conditions. Remarkably, in these assays, we found a close correlation between arginylation and aging, a discovery that we believe has longer-term implications in uncovering the importance of ATE1 in normal biology and disease therapies. Here we describe the original methods we used to measure ATE1 activity in tissues and correlate it with key biological events. PMID- 26285880 TI - Assaying the Posttranslational Arginylation of Proteins in Cultured Cells. AB - To evaluate the posttranslational arginylation of proteins in vivo, we describe a protocol for studying the (14)C-Arg incorporation into proteins of cells in culture. The conditions determined for this particular modification contemplate both the biochemical requirements of the enzyme ATE1 and the adjustments that allowed the discrimination between posttranslational arginylation of proteins and de novo synthesis. These conditions are applicable for different cell lines or primary cultures, representing an optimal procedure for the identification and the validation of putative ATE1 substrates. PMID- 26285881 TI - Assaying ATE1 Activity in Yeast by beta-Gal Degradation. AB - In 1980s it was found that addition of N-terminal Arg to proteins induces their ubiquitination and degradation by the N-end rule pathway. While this mechanism applies only to the proteins which also have other features of the N-degron (including a closely adjacent Lys that is accessible for ubiquitination), several test substrates have been found to follow this mechanism very efficiently after ATE1-dependent arginylation. Such property enabled researchers to test ATE1 activity in cells indirectly by assaying for the degradation of such arginylation dependent substrates. The most commonly used substrate for this assay is E. coli beta galactosidase (beta-Gal) because its activity can be easily measured using standardized colorimetric assays. Here we describe this method, which has served as a quick and easy way to characterize ATE1 activity during identification of arginyltransferases in different species. PMID- 26285882 TI - Bacterial Expression and Purification of Recombinant Arginyltransferase (ATE1) and Arg-tRNA Synthetase (RRS) for Arginylation Assays. AB - Here we describe the procedure for expression and purification of recombinant ATE1 from E. coli. This method is easy and convenient and can result in one-step isolation of milligram amounts of soluble enzymatically active ATE1 at nearly 99 % purity. We also describe a procedure for expression and purification of E. coli Arg-tRNA synthetase essential for the arginylation assays described in the next two chapters. PMID- 26285883 TI - Assaying ATE1 Activity In Vitro. AB - Here we describe a standard arginyltransferase assay in vitro using bacterially expressed purified ATE1 in a system with minimal number of components (Arg, tRNA, Arg-tRNA synthetase, and arginylation substrate). Assays of this type have first been developed in the 1980s using crude ATE1 preparations from cells and tissues and then perfected recently for the use with bacterially expressed recombinant protein. This assay represents a simple and efficient way to measure ATE1 activity. PMID- 26285884 TI - High-Throughput Arginylation Assay in Microplate Format. AB - Here we describe the biochemical assay for ATE1-mediated arginylation in microplate format, which can be applied to high-throughput screens for identification of small-molecule inhibitors and activators of ATE1, high-volume analysis of ATE1 substrates, and other similar applications. Originally, we have applied this screen to a library of 3280 compounds and identified two compounds which specifically affect ATE1-regulated processes in vitro and in vivo. The assay is based on in vitro ATE1-mediated arginylation of beta-actin's N-terminal peptide, but it can also be applied using other ATE1 substrates. PMID- 26285885 TI - Assay of Arginyltransferase Activity by a Fluorescent HPLC Method. AB - Syntheses of fluorescent substrate and product for arginyltransferase, N-aspartyl N'-dansylamido-1,4-butanediamine (Asp-4DNS), and N-arginylaspartyl-N'-dansylamido 1,4-butanediamine (ArgAsp-4DNS), respectively, including their precursor 4 dansylamidobutylamine (4DNS), are described. Then, HPLC conditions are summarized for a baseline separation of the three compounds in 10 min. The present method, which permits the simultaneous determination of Asp-4DNS, 4DNS, and ArgAsp-4DNS (in eluting order), is advantageous in measuring arginyltransferase activity and detecting the unfavorable enzyme(s) in 105,000 * g supernatant of tissues to ensure accurate determination. PMID- 26285886 TI - Identification of Arginylated Proteins by Mass Spectrometry. AB - Here we describe the method for identification of arginylated proteins by mass spectrometry. This method has been originally applied to the identification of N terminally added Arg on proteins and peptides, and then expanded to identification of side chain arginylation which has been recently described by our groups. The key steps in this method include the use of the mass spectrometry instruments that can identify peptides with very high pass accuracy (Orbitrap) and apply stringent mass cutoffs during automated data analysis, followed by manual validation of the identified spectra. These methods can be used with both complex and purified protein samples and, to date, constitute the only reliable way to confirm arginylation at a particular site on a protein or peptide. PMID- 26285887 TI - Analysis of Arginylated Peptides by Subtractive Edman Degradation. AB - During the early studies of N-terminal arginylation, Edman degradation was widely used to identify N-terminally added Arg on protein substrates. This old method is reliable but highly depends on the purity and abundance of samples and can become misleading unless a highly purified, highly arginylated protein can be obtained. Here we report a mass spectrometry-based method that utilizes Edman degradation chemistry to identify arginylation in more complex and less abundant protein samples. This method can also apply to the analysis of other posttranslational modifications. PMID- 26285888 TI - Transferase-Mediated Labeling of Protein N-Termini with Click Chemistry Handles. AB - The E. coli aminoacyl transferase (AaT) can be used to transfer a variety of unnatural amino acids, including those with azide or alkyne groups, to the alpha amine of a protein with an N-terminal Lys or Arg. Subsequent functionalization through either copper-catalyzed or strain-promoted click reactions can be used to label the protein with fluorophores or biotin. This method can be used to directly detect AaT substrates or in a two-step protocol to detect substrates of the mammalian ATE1 transferase. PMID- 26285889 TI - Applying Arginylation for Bottom-Up Proteomics. AB - Arginylation is an enzymatic reaction in which arginyl-tRNA protein transferase 1 (ATE1, EC 2.3.2.8) conjugates a single arginyl moiety from aminoacylated tRNA(Arg) onto a target polypeptide. We established arginylation for in vitro labeling of peptides with N-terminal acidic amino acids. Consistent with prior knowledge, arginylated peptides flanked by basic amino acids result in rich redundant MS/MS fragment spectra using various precursor fragmentation modes. Arginylation carried out by ATE1 is a fast method for labeling peptides. Sequence specific proteolytic digest of proteins is best carried out using a double digest of proteins by Lys-C and Asp-N to generate peptides with a basic amino acid on the C-terminus and an acidic amino acid on the N-terminus. Under these conditions, arginylation is specific for N-terminal acidic amino acids and results in a near 2* sequence coverage in the MS/MS spectrum are achieved. PMID- 26285890 TI - Development of New Tools for the Studies of Protein Arginylation. AB - Studies of posttranslational modifications present many unique challenges, stemming from their role as the major drivers of biological complexity. Perhaps the most immediate challenge to researchers working on virtually any posttranslational modification is the shortage of reliable easy-to-use tools that can enable massive identification and characterization of posttranslationally modified proteins, as well as their functional modulation in vitro and in vivo. In the case of protein arginylation, which utilizes charged Arg-tRNA that is also used by the ribosomes, detection and labeling of arginylated proteins are especially difficult, because of the necessity of distinguishing these proteins from the products of conventional translation. As of now, this difficulty remains the major obstacle to new researchers entering the field. This chapter discusses some of the strategies for developing antibodies for arginylation detection, as well as some general considerations for development of other tools for the studies of arginylation. PMID- 26285891 TI - Current Challenges in Stem Cell Transplantation in Myelofibrosis. AB - Primary or post-ET/PV myelofibrosis is one of the Philadelphia-negative myeloproliferative neoplasms with worst survival. Allogeneic stem cell transplantation (ASCT) can cure a substantial number of patients but is still not universally applicable due to toxicity which leads to therapy-related morbidity and mortality. In the more recent years, outcome of ASCT has improved by less toxic conditioning regimens and optimization of relapse prevention strategies. The introduction of novel therapies such as JAK2 inhibitors may also be helpful in preparation of the transplant by reducing spleen size and constitutional symptoms. To reduce the risk of relapse, molecular monitoring and adoptive immunotherapy with donor lymphocytes have been introduced. Despite lacking prospective randomized trials, it is justified to offer ASCT to eligible patients with PMF whose median survival is expected to be less than 5 years. This includes patients with intermediate-2 and high risk according to IPSS or DIPSS, respectively. The benefit/risk ratio should be considered in each patient taking also transplant- and patient-specific factors into account. PMID- 26285892 TI - Evaluation of antireflux surgery using multichannel intraluminal impedance-pH measurement in neurologically impaired patients. AB - PURPOSE: This study aimed to evaluate esophageal function before and after antireflux surgery (ARS) in neurologically impaired (NI) patients using 24 h multichannel intraluminal impedance (MII)-pH measurement. METHODS: Seven NI patients (age, 0-33 years; median, 13 years) were assessed before and after ARS using 24 h MII-pH. We described reflux parameters such as pH reflux index, bolus exposure index, number of acidic and nonacidic reflux episodes, mean acid clearance time and median bolus clearance time, and esophageal motility parameters in dry swallows such as bolus presence time (BPT), total bolus transit time (TBTT), and total propagation velocity (TPV). RESULTS: The postoperative reflux parameters such as pH reflux index, acid clearance time, bolus exposure index, and the number of acidic reflux episodes significantly decreased (P < 0.05) compared with the preoperative ones. The esophageal motility parameters including all sites of BPTs, TBTT, and TPV did not change in the MII-pH measurement after ARS (P = non-significant). CONCLUSION: ARS effectively reduced gastro-esophageal reflux (GER) in NI patients without the impairment of esophageal motility by MII-pH measurement. MII-pH was useful to detect the subtype of GER before and after ARS and appeared to be appropriate for evaluating esophageal motility. PMID- 26285893 TI - Laparoscopic Toupet fundoplication for gastroesophageal reflux: a series of 131 neurologically impaired pediatric cases at a single children's hospital. AB - PURPOSE: To present the medium to long-term outcome of the largest pediatric series of laparoscopic Toupet fundoplications (LTF) performed at a single institution. PATIENTS AND METHODS: Subjects were 131 neurologically impaired children (81 M, 50 F) who underwent LTF between 2003 and 2013. Our LTF involves full dissection of the crus of the diaphragm to allow the intraabdominal esophagus to be mobilized at least 3-4 cm. RESULTS: Preoperative mean fraction time for pH <4 was 14.6 %. Mean age at LTF was 6.7 years (3 months-18 years). Mean duration of follow-up was 5.7 years (range 1.2-12.1 years). One case required conversion to open surgery. Intra-operative complications were all injuries to the esophagus/gastric wall (n = 4; 3.0 %) including full-thickness perforation (n = 1; 0.8 %). Postoperative complications included pyloric stenosis (n = 4; 3.0 %), dysphagia (n = 1; 0.8 %), incisional hernia (n = 1; 0.8 %), hemorrhage requiring transfusion (n = 1; 0.8 %), recurrence (n = 3; 2.3 % at 11, 13, and 48 months, respectively), and gastrostomy site infection (n = 7; 5.3 %). Mean operative time decreased significantly with experience from 180.8 min for the first quarter of subjects to 150.6 (2nd quarter), 128.6 (3rd) and 109.2 min (4th). CONCLUSIONS: Our LTF would appear to be safe for treating GERD in children because of reliable outcome and low recurrence. PMID- 26285894 TI - Ureteric patency after Deflux(r) injection for the treatment of vesicoureteric reflux in children confirmed by a novel epidural catheter-assisted endoscopic technique. AB - PURPOSE: We present EDCAT (epidural catheter-assisted Deflux((r)) treatment) for treating vesicoureteral reflux (VUR) and confirming ureteric patency after Deflux((r)) treatment. METHODS: We treated 147 ureters in 101 children (M:F 62:39; VUR <= grade III: n = 72; VUR >= grade IV: n = 75) using EDCAT between 2011 and 2014. EDCAT involves injecting 1-3 mL of diluted indigo carmine solution through an epidural anesthesia catheter inserted into the Deflux((r))-treated ureter and observing for up to 15 min to confirm patency. RESULTS: For EDCAT, mean age was 4.9 years and mean operative time was 30.1 +/- 12.1 min; overall cure of VUR after initial treatment was 87.7 % for VUR grades I-V, 88.9 % for VUR <= grade III, and 86.6 % for VUR >= grade IV; VUR was cured in 129/147 after 1 treatment, 7/18 after 2 treatments, 7/11 after 3 treatments, and persistent in 4/4. We experienced 1 case of obstruction after an EDCAT catheter was removed before confirming patency. EDCAT catheters were left overnight in 2 ureters in 2 cases when patency could not be confirmed after 15 min to prevent obstruction. Both did not develop obstruction. Four ureters with recurrence of VUR (all grade <= II) are being observed. CONCLUSION: EDCAT allows ureteric patency to be confirmed immediately and prevents obstruction. PMID- 26285896 TI - [Not Available]. PMID- 26285895 TI - Anterior mediastinal tracheostomy with a median mandibular splitting approach in a Larsen syndrome patient with posterior cervical arthrodesis. AB - Larsen syndrome is a rare congenital connective tissue disorder characterized by multiple joint dislocations. A novel anterior mediastinal tracheostomy with a median mandibular splitting approach is presented for the treatment of airway obstruction in a Larsen syndrome patient with posterior cervical arthrodesis. PMID- 26285897 TI - [Contact allergies in the elderly]. AB - The percentage of seniors (> 65 years of age) in the general population continues to rise. Their sensitization profile may be influenced by lifelong work-related and nonwork-related exposures and comorbidities requiring local or systemic treatment. Recent analysis of the IVDK (Information Network of Departments of Dermatology) cohort concerning the most frequently recognized contact allergens in the age group above 65 (2009-2013: N = 14,841) revealed significant differences compared to the age group up to 65 years of age. The top 10 contact allergens recognized in individuals older than 65 years were the following: fragrance mix, Myroxylon pereirae (Balsam of Peru), nickel (II) sulfate, fragrance mix II, colophony, propolis, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), lanolin alcohol, Amerchol L 101, tert-butylhydroquinone. Sensitization to nickel was significantly less frequent, while sensitizations to fragrance mix and Balsam of Peru were significantly more frequent than in the age group up to 65 years of age. The percentage of patients with leg dermatitis was 25.9 % in the age group above 65 (versus 5.8 % in the age group up to 65 years of age). The analysis of the subgroup over 65 years of age with and without ulcer/stasis dermatitis/chronic venous insufficiency displayed remarkable differences in sensitization frequencies against ingredients of topical ointments (lanolin alcohol, Amerchol L 101, and tert-butylhydroquinone). If these comorbidities exist, patch testing of the topical ointment series parallel to the standard series is worthwhile. PMID- 26285898 TI - [Not Available]. AB - Allergic contact eczema in children is frequent. If clinically suspected, a patch test should be performed. In the present study, data obtained from 116,742 patients who had undergone a patch test from 2005-2014 were analysed. The children group (range 0-12 years) included 925 patients. If at least 700 tested individuals were considered, the most frequent sensitizations in this group were nickel sulfate (8.5 %), fragrance mix I (5.5 %), and colophony (3.4 %), whereby sensitisation in adults was higher for nickel sulfate (15.5 %) and fragrance mix 1 (8.4 %), while being similar for colophony (3.7 %). In adolescents with and without a profession, nickel sulfate (11.1 and 13.6 %, respectively) and cobalt (II) chloride (3.9 and 3.4 %, respectively) were the most frequent positively tested contact allergens. Sensitisations toward fragrance mix I was low (3.9 and 3.4 %, respectively) in comparison to the adult group (8.4 %). In both children and adolescents, toluene diamine and paraphenylenediamine sensitizations were not infrequent, but it must be considered that these allergens were only tested if suspected. The data show that the sensitisation profile among children and adolescents display patterns similar to those in adults. Sensitisations in childhood and adolescence towards dyes like paraphenylendiamine may be associated with increased use of tattooing in these groups. PMID- 26285899 TI - The effect of iterative model reconstruction on coronary artery calcium quantification. AB - Coronary artery calcium (CAC) scoring with computed tomography (CT) is an established tool for quantifying calcified atherosclerotic plaque burden. Despite the widespread use of novel image reconstruction techniques in CT, the effect of iterative model reconstruction on CAC score remains unclear. We sought to assess the impact of iterative model based reconstruction (IMR) on coronary artery calcium quantification as compared to the standard filtered back projection (FBP) algorithm and hybrid iterative reconstruction (HIR). In addition, we aimed to simulate the impact of iterative reconstruction techniques on calcium scoring based risk stratification of a larger asymptomatic population. We studied 63 individuals who underwent CAC scoring. Images were reconstructed with FBP, HIR and IMR and CAC scores were measured. We estimated the cardiovascular risk reclassification rate of IMR versus HIR and FBP in a larger asymptomatic population (n = 504). The median CAC scores were 147.7 (IQR 9.6-582.9), 107.0 (IQR 5.9-526.6) and 115.1 (IQR 9.3-508.3) for FBP, HIR and IMR, respectively. The HIR and IMR resulted in lower CAC scores as compared to FBP (both p < 0.001), however there was no difference between HIR and IMR (p = 0.855). The CAC score decreased by 7.2 % in HIR and 7.3 % in IMR as compared to FBP, resulting in a risk reclassification rate of 2.4 % for both HIR and IMR. The utilization of IMR for CAC scoring reduces the measured calcium quantity. However, the CAC score based risk stratification demonstrated modest reclassification in IMR and HIR versus FBP. PMID- 26285900 TI - Up-Regulation of CCT8 Related to Neuronal Apoptosis after Traumatic Brain Injury in Adult Rats. AB - Traumatic brain injury (TBI) initiates a series of neurochemical and signaling changes that could eventually lead to neuronal apoptosis. Recent studies indicated that mature neurons cell cycle re-enter played a crucial role in neuronal apoptosis. In this study, we identified that the chaperonin containing TCP-1, subunit 8 (CCT8), as a member of class II chaperonins, was significantly upregulated following TBI. Moreover, double immunofluorescence staining revealed that CCT8 was co-expressed with neuronal nuclei (NeuN). Besides, co-localization of CCT8/active caspase 3 was detected in NeuN. We also examined the expression profiles of active caspase 3 whose changes were correlated with the expression of CCT8. All our findings suggested that CCT8 might be involved in the pathophysiology of brain after TBI. PMID- 26285901 TI - Magnesium Lithospermate B Protects Neurons Against Amyloid beta (1-42)-Induced Neurotoxicity Through the NF-kappaB Pathway. AB - Magnesium lithospermate B (MLB) is one of the major bioactive components of Radix Salviae miltiorrhizae, a Chinese traditional herbal medicine colloquially known as Dan Shen. In this study, we investigated the neuroprotective effect of MLB against oligomeric amyloid beta (Abeta) (1-42)-induced neurotoxicity in cultured FVB mouse hippocampal neurons. We found that pretreatment with MLB not only prevents a loss in neuronal cell viability following exposure to Abeta (1-42), but also attenuates Abeta (1-42)-induced release of pro-inflammatory cytokines and neuronal apoptosis in a dose-dependent manner. Mechanistic studies show that MLB counteracts Abeta (1-42)-induced activation of the nuclear factor kappa B (NF kappaB) pathway, evidenced by the suppression of NF-kappaB luciferase reporters, decreased expression of phosphorylated Inhibitor kappaB alpha and IkappaB kinase alpha, and reduced nuclear translocation of p65 in response to pre-treatment with 50 MUg/ml MLB prior to Abeta (1-42) exposure. MLB was able to reverse the increase in phosphorylated c-Jun N-terminal kinase (JNK) levels as well as the decrease in phosphorylated Akt levels that are induced by Abeta (1-42), although this finding did not extend to extracellular signal-regulated kinase or p38 kinases. Furthermore, combining MLB with the JNK inhibitor SP600125 synergistically counteracts the Abeta (1-42)-induced reduction in cell viability and neurite growth, and the neuroprotective effects of MLB could be attenuated by the Akt inhibitor triciribine. In conclusion, these results suggest that MLB can protect against Abeta (1-42)-induced neuronal damage, which is most likely to be mediated by the NK-kappaB pathway. PMID- 26285902 TI - Differential Expression of AQP1 and AQP4 in Avascular Chick Retina Exposed to Moderate Light of Variable Photoperiods. AB - Aquaporins (AQPs) are integral membrane proteins which maintain cellular water and ion homeostasis. Alterations in AQP expression have been reported in rod dominated rodent retinas exposed to light. In rodents and also in birds, light of moderate intensities (700-2000 lux) damages the retina, though detailed changes were not examined in birds. The aim of our study was to see if light affects cone dominated retinas, which would be reflected in expression levels of AQPs. We examined AQP1 and AQP4 expressions in chick retina exposed to 2000 lux under 12 h light:12 h dark (12L:12D; normal photoperiod), 18L:6D (prolonged photoperiod) and 24L:0D (constant light). Additionally, morphological changes, apoptosis (by TUNEL) and levels of glutamate and GFAP (a marker of injury) in the retina were examined to correlate these with AQP expressions. Constant light caused damage in outer and inner nuclear layer (ONL, INL) and ganglion cell layer (GCL). Also, there were associated increases in GFAP and glutamate levels in retinal extracts. In normal photoperiod, AQP1 was expressed in GCL, outer part of INL and photoreceptor inner segments of. AQP4 was additionally expressed in nerve fiber layer. Immunohistochemistry and Western blotting revealed over all decreased AQP1 and AQP4 expression in constant light condition compared to those in other two groups. The elevated GFAP and glutamate levels might be involved in the reduction of AQPs in constant light group. Such decreases in AQP expressions are perhaps linked with retinal cell damage seen in constant light condition, while their relatively enhanced expression in two other conditions may help in maintaining a normal retinal architecture, indicating their neuroprotective potential. PMID- 26285903 TI - Combined Strategy for a Reliable Evaluation of Spinal Cord Injury Using an in vivo Model. AB - BACKGROUND: A complete neurological exam contributes in establishing spinal cord injury severity and its extent by identifying the damage to the sensory and motor pathways involved in order to address a more case-specific and precise pharmacological therapy. However, assessment of neurologic function in spinal cord injury models is usually reported by using sensory or motor tests independently. METHODS: A reliable integral method is needed to precisely evaluate location and severity of the injury at baseline and, in further assessments, to establish the degree of spontaneous recovery. A combination of sensation-based tests and motor-based tests was used to evaluate impaired neurologic function after spinal cord injury and the degree of spontaneous recovery, in different stages, on an in vivo model. RESULTS: Combined neurologic evaluation was useful to establish location and severity of the injury in all animals and also to detect degrees of spontaneous recovery at different stages after the injury. Comparisons of neurological function were assessed in time-days and groups between BBB motor score, latency maintenance of posture, locomotion and latency presentation of grooming before and after the injury. Our results suggest that a combined assessment strategy, including sensory and motor tests, can lead to better evaluation of spinal cord injury severity and location, and documentation of the extent of spontaneous recovery following SCI and identify specific motor and sensory pathway integrity. CONCLUSION: In conclusion, a combined assessment strategy provides a concise method for evaluating the impact of interventions in experimental models of SCI. PMID- 26285904 TI - Distribution and Size Relationships of Plastic Marine Debris on Beaches in South Korea. AB - The characteristics of the distribution of plastic marine debris were determined on 12 beaches in South Korea in 2013 and 2014. The abundances of large micro- (1 5 mm), meso- (5-25 mm), and macroplastics (>25 mm) were 880.4, 37.7, and 1.0 particles/m(2), respectively. Styrofoam was the most abundant debris type for large microplastics and mesoplastics (99.1 and 90.9 %, respectively). Fiber (including fabric) was the most abundant of the macroplastics (54.7 %). There were no statistical differences in the mean numbers and weights of plastic debris among three beach groups from west, south, and east coasts. No significant differences were detected between the abundances of beached plastics in high strandline and backshore for all three size groups. Spearman's rank correlation was used to determine the relationships between the three debris size classes. The abundance of large microplastics was strongly correlated with that of mesoplastics for most material types, which suggests that the contamination level of large microplastics can be estimated from that of mesoplastics. As surveying of smaller particles is more labor intensive, the surveying of mesoplastics with a 5-mm sieve is an efficient and useful way to determine "hot-spots" on beaches contaminated with large microplastics. PMID- 26285905 TI - Sex and age effects on cardiovascular autonomic function in healthy adults. AB - PURPOSE: To determine the effects of sex and age on cardiovascular autonomic parameters in healthy adults as assessed by Finapres (finger arterial pressure) method and prolonged head-up tilt (HUT). METHODS: We enrolled 81 healthy volunteers (41 females, 40 males, 18-74 years) for extensive cardiovascular autonomic function testing including blood pressure (BP) recordings, electrocardiography, and impedance cardiography at rest, under 60 degrees HUT for 45 min, active standing for 5 min, Valsalva maneuver, and deep breathing (DB). Mean values and orthostatic changes, i.e., differences to baseline, of heart rate (HR), systolic and diastolic BP, stroke volume (SV), and total peripheral resistance (TPR), as well as DB ratio and Valsalva ratio were calculated. A generalized linear model (extended by generalized estimating equations) was used to assess sex- and age-related differences. RESULTS: Mean HR at rest was higher in women than in men (p = 0.035). In men, we observed significantly higher mean BP at rest (p < 0.001 systolic and p = 0.004 diastolic) and during HUT (p = 0.001 systolic and p < 0.001 diastolic), mean TPR at rest (p = 0.034), and mean SV during HUT (p < 0.001). We found no significant impact of sex on orthostatic changes of HR and BP. Mean TPR during HUT increased with age (p = 0.001), particularly in older women. Orthostatic changes of HR and diastolic BP, DB ratio, and Valsalva ratio became attenuated with age (p = 0.018, p = 0.006, p < 0.001, and p < 0.001, respectively). CONCLUSIONS: Our study suggests that aging rather than sex needs to be taken into account when interpreting HR and BP changes during prolonged HUT performance. PMID- 26285906 TI - Iodide transport and breast cancer. AB - Breast cancer is the second most common cancer worldwide and the leading cause of cancer death in women, with incidence rates that continue to rise. The heterogeneity of the disease makes breast cancer exceptionally difficult to treat, particularly for those patients with triple-negative disease. To address the therapeutic complexity of these tumours, new strategies for diagnosis and treatment are urgently required. The ability of lactating and malignant breast cells to uptake and transport iodide has led to the hypothesis that radioiodide therapy could be a potentially viable treatment for many breast cancer patients. Understanding how iodide is transported, and the factors regulating the expression and function of the proteins responsible for iodide transport, is critical for translating this hypothesis into reality. This review covers the three known iodide transporters - the sodium iodide symporter, pendrin and the sodium-coupled monocarboxylate transporter - and their role in iodide transport in breast cells, along with efforts to manipulate them to increase the potential for radioiodide therapy as a treatment for breast cancer. PMID- 26285908 TI - New lipoxygenase and cholinesterase inhibitory sphingolipids from Carthamus oxyacantha. AB - Two new sphingolipids: oxyacanthin A [(2S,3S,4R)-2-{[(2R,5E)-2-hydroxyoctadec-5 enoyl]amino}hexaeicosane-1,3,4-triol; 1] and B [(2S,3S,4R)-2-{[(2R,5E)-2 hydroxyoctadec-5-enoyl]amino}hexaeicosane-1,3,4-triol-1-O-beta-D-glucopyranoside; 2], together with 1-octacosanol, beta-sitosterol, beta-sitosterol 3-O-beta-D glucopyranoside and luteolin 7-O-beta-glucopyranoside were isolated from the methanolic extract of the whole plant of Carthamus oxyacantha. Their structures were elucidated using (1)H and (13)C NMR spectra and 2D NMR analyses (HMQC, HMBC and COSY) in combination with mass spectrometry (EI-MS, HR-EI-MS, FAB-MS and HR FAB-MS) experiments and in comparison with the literature data of the related compounds. Both the compounds 1 and 2 showed inhibitory potential against lipoxygenase (LOX) in a concentration-dependent manner with IC50 values 83.3 +/- 1.3 and 245.7 +/- 1.1 uM, whereas compound 2 showed inhibition against enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values 65.3 +/- 0.1 and 93.6 +/- 0.1 uM, respectively. PMID- 26285907 TI - STAT4 contributes to adipose tissue inflammation and atherosclerosis. AB - Adipose tissue (AT) inflammation is an emerging factor contributing to cardiovascular disease. STAT4 is a transcription factor expressed in adipocytes and in immune cells and contributes to AT inflammation and insulin resistance in obesity. The objective of this study was to determine the effect of STAT4 deficiency on visceral and peri-aortic AT inflammation in a model of atherosclerosis without obesity. Stat4(-/-)Apoe(-/-) mice and Apoe(-/-) controls were kept either on chow or Western diet for 12 weeks. Visceral and peri-aortic AT were collected and analyzed for immune composition by flow cytometry and for cytokine/chemokine expression by real-time PCR. Stat4(-/-)Apoe(-/-) and Apoe(-/-) mice had similar body weight, plasma glucose, and lipids. Western diet significantly increased macrophage, CD4+, CD8+, and NK cells in peri-aortic and visceral fat in Apoe(-/-) mice. In contrast, in Stat4(-/-)Apoe(-/-) mice, a Western diet failed to increase the percentage of immune cells infiltrating the AT. Also, IL12p40, TNFa, CCL5, CXCL10, and CX3CL1 were significantly reduced in the peri-aortic fat in Stat4(-/-)Apoe(-/-) mice. Importantly, Stat4(-/-)Apoe(-/-) mice on a Western diet had significantly reduced plaque burden vs Apoe(-/-) controls. In conclusion, STAT4 deletion reduces inflammation in peri-vascular and visceral AT and this may contribute via direct or indirect effects to reduced atheroma formation. PMID- 26285910 TI - Endovascular Management of Refractory Hepatic Encephalopathy Complication of Transjugular Intrahepatic Portosystemic Shunt (TIPS): Comprehensive Review and Clinical Practice Algorithm. AB - Transjugular intrahepatic portosystemic shunt (TIPS) has evolved as an effective intervention for treatment of complications of portal hypertension. The use of polytetrafluoroethylene-covered stents have improved the patency of the shunts and diminished the incidence of TIPS dysfunction. However, TIPS-related refractory hepatic encephalopathy (rHE) poses a significant challenge. Approximately 3-7 % of patients with TIPS develop rHE. Refractory hepatic encephalopathy is defined as a recurrent or persistent encephalopathy despite appropriate medical treatment. Hepatic encephalopathy can be an extremely debilitating complication that profoundly affects quality of life. The approach to management of patients with rHE is complex and typically requires collaboration between different specialties. Liver transplantation is the ultimate treatment for rHE; however, the ongoing shortage of organ donation markedly limits this treatment option. Alternative therapies such as shunt occlusion or reduction can control symptoms and serve as a 'bridge' therapy to liver transplantation. Therefore, interventional radiologists play a key role in the management of these patients by offering a variety of endovascular techniques. The purpose of this review is to highlight some of these endovascular techniques and to develop a therapeutic algorithm that can be applied in clinical practice for the management of rHE. PMID- 26285911 TI - Reply. PMID- 26285909 TI - Mutations of Epigenetic Modifier Genes as a Poor Prognostic Factor in Acute Promyelocytic Leukemia Under Treatment With All-Trans Retinoic Acid and Arsenic Trioxide. AB - BACKGROUND: Acute promyelocytic leukemia (APL) is a model for synergistic target cancer therapy using all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), which yields a very high 5-year overall survival (OS) rate of 85 to 90%. Nevertheless, about 15% of APL patients still get early death or relapse. We performed this study to address the possible impact of additional gene mutations on the outcome of APL. METHODS: We included a consecutive series of 266 cases as training group, and then validated the results in a testing group of 269 patients to investigate the potential prognostic gene mutations, including FLT3-ITD or TKD, N-RAS, C-KIT, NPM1, CEPBA, WT1, ASXL1, DNMT3A, MLL (fusions and PTD), IDH1, IDH2 and TET2. RESULTS: More high-risk patients (50.4%) carried additional mutations, as compared with intermediate- and low-risk ones. The mutations of epigenetic modifier genes were associated with poor prognosis in terms of disease free survival in both training (HR = 6.761, 95% CI 2.179-20.984; P = 0.001) and validation (HR = 4.026, 95% CI 1.089-14.878; P = 0.037) groups. Sanz risk stratification was associated with CR induction and OS. CONCLUSION: In an era of ATRA/ATO treatment, both molecular markers and clinical parameter based stratification systems should be used as prognostic factors for APL. PMID- 26285912 TI - Pimenta pseudocaryophyllus Derivatives: Extraction Methods and Bioactivity Against Sitophilus zeamais Motschulsky (Coleoptera: Curculionidae). AB - Plant-based insecticides can play an important role in integrated insect pest management (IPM), especially in protecting stored grains. The aim of this study was to evaluate the bioactivity of derivatives (powder, ethanolic extract, and essential oil (EO)) from the leaves of Pimenta pseudocaryophyllus (Myrtaceae), a Brazilian native species, against Sitophilus zeamais Motschulsky (Coleoptera: Curculionidae), the main insect pest of stored corn. The powder and essential oil prepared from leaves showed a repellent effect. Moreover, the EO exhibited promising insecticidal activity through residual contact (LC50 = 1522 mg kg(-1)) and significantly decreased the F 1 progeny and the percentage of damaged grains. However, the essential oil obtained from P. pseudocaryophyllus leaves did not result in significant mortality of S. zeamais adults after 72 h of exposure by fumigation in concentrations up to 400 MUL L(-1) of air. Based on GC-MS analysis, 20 compounds were identified in the essential oil of P. pseudocaryophyllus leaves, being chavibetol (38.14%), methyl eugenol (11.35%), and terpinolene (9.17%) as the major constituents. Essential oil from P. pseudocaryophyllus leaves is an interesting source of compounds with grain-protectant properties and should be analyzed in future studies aiming to develop new bioinsecticides to use in the IPM of stored grains. PMID- 26285913 TI - In Vivo Identification and Induction of Articular Cartilage Stem Cells by Inhibiting NF-kappaB Signaling in Osteoarthritis. AB - Osteoarthritis (OA) is a highly prevalent and debilitating joint disorder characterized by the degeneration of articular cartilage. However, no effective medical therapy has been found yet for such condition. In this study, we directly confirmed the existence of articular cartilage stem cells (ACSCs) in vivo and in situ for the first time both in normal and OA articular cartilage, and explored their chondrogenesis in Interleukin-1beta (IL-1beta) induced inflammation environment and disclose whether the inhibition of NF-kappaB signaling can induce ACSCs activation thus improve the progression of experimental OA. We found an interesting phenomenon that ACSCs were activated and exhibited a transient proliferative response in early OA as an initial attempt for self-repair. During the in vitro mechanism study, we discovered IL-1beta can efficiently activate the NF-kappaB pathway and potently impair the responsiveness of ACSCs, whereas the NF kappaB pathway inhibitor rescued the ACSCs chondrogenesis. The final in vivo experiments further confirmed ACSCs' activation were maintained by NF-kappaB pathway inhibitor, which induced cartilage regeneration, and protected articular cartilage from injury in an OA animal model. Our results provided in vivo evidence of the presence of ACSCs, and disclosed their action in the early OA stage and gradual quiet as OA process, presented a potential mechanism for both cartilage intrinsic repair and its final degradation, and demonstrated the feasibility of inducing endogenous adult tissue-specific mesenchymal stem cells for articular cartilage repair and OA therapy. PMID- 26285914 TI - Genetic Structure across Broad Spatial and Temporal Scales: Rocky Mountain Tailed Frogs (Ascaphus montanus; Anura: Ascaphidae) in the Inland Temperate Rainforest. AB - Contemporary and historical processes interact to structure genetic variation, however discerning between these can be difficult. Here, we analyze range-wide variation at 13 microsatellite loci in 2098 Rocky Mountain tailed frogs, Ascaphus montanus, collected from 117 streams across the species distribution in the Inland Northwest (INW) and interpret that variation in light of historical phylogeography, contemporary landscape genetics, and the reconstructed paleodistribution of the species. Further, we project species distribution models (SDMs) to predict future changes in the range as a function of changing climate. Genetic structure has a strong spatial signature that is precisely congruent with a deep (~1.8 MY) phylogeographic split in mtDNA when we partition populations into 2 clusters (K = 2), and is congruent with refugia areas inferred from our paleorange reconstructions. There is a hierarchical pattern of geographic structure as we permit additional clusters, with populations clustering following mountain ranges. Nevertheless, genetic diversity is the highest in populations at the center of the range and is attenuated in populations closer to the range edges. Similarly, geographic distance is the single best predictor of pairwise genetic differentiation, but connectivity also is an important predictor. At intermediate and local geographic scales, deviations from isolation-by-distance are more apparent, at least in the northern portion of the distribution. These results indicate that both historical and landscape factors are contributing to the genetic structure and diversity of tailed frogs in the Inland Northwest. PMID- 26285916 TI - The Transition States for CO2 Capture by Substituted Ethanolamines. AB - Quantum chemical studies are used to understand the electronic and steric effects on the mechanisms of the reaction of substituted ethanolamines with CO2. SCS MP2/6-311+G(2d,2p) calculations are used to obtain the activation energy barriers and reaction energies for both the carbamate and bicarbonate formation. Implicit solvent effects are included with the universal solvation model SMD. Carbamate formation is more favorable than bicarbonate formation for monoethanolamine (MEA) both kinetically and thermodynamically. Increase of the steric hindrance on the C atoms around the N atom in substituted ethanolamines favors bicarbonate formation over carbamate formation with lower activation barriers and thereby higher reaction rates. In contrast, substitution by an N-methyl or N-ethyl group on MEA leads to a lower activation barrier for both carbamate formation and bicarbonate formation. As a result, higher reaction rates are expected as compared to MEA, and therefore these compounds have significant potential as industrial CO2 capturing solvents. PMID- 26285915 TI - Different DMRT3 Genotypes Are Best Adapted for Harness Racing and Riding in Finnhorses. AB - Previous studies showed a positive effect of the DMRT3 "gait keeper" mutation on harness racing performance in Standardbreds, French-, and Nordic trotters. The mutation has also been shown to influence riding traits in multiple breeds. This study investigated the effect of the DMRT3 mutation on harness racing performance and riding traits in Finnhorses. Finnhorses used for harness racing (n = 180) and for riding (n = 59) were genotyped for the DMRT3 mutation. For the trotters the genotypes were evaluated for association with racing performance (number of starts, victories, placings, earnings, and race times). At 3-6 years of age the AA genotype was superior compared with the CA and CC genotypes. The AA horses had a significantly higher proportion of victories (P = 1.4*10(-6)) and placings (P = 4.1*10(-7)), better race times (P = 0.01), and earned more money (P = 0.009) compared with C-horses. For the Finnhorses used for riding the owners answered a questionnaire to score how well the horse performed the gaits walk, trot, and canter on a scale from 1 to 6. These scores were tested for association with the DMRT3 genotypes. Although AA horses were more successful as racehorses, the CC and CA horses appear more adapted for classical riding disciplines. The AA horses received significantly lower gait scores compared with C-horses for the majority of gaits. Except for rhythm in extended canter (P = 0.05), there were no significant differences between CA and CC horses. This study shows that there are different optimal genotypes for different disciplines and the DMRT3 mutation clearly influences gaits and performance in Finnhorses. PMID- 26285917 TI - The epidemiological feedbacks critical to the evolution of host immunity. AB - We examine in detail how epidemiological feedbacks combine with costs and benefits to determine the evolution of resistance by systematically analysing continuously stable strategies (CSS) for different host-parasite frameworks. The mode of resistance (innate versus acquired), the nature of the host (i.e. life history and immunological memory) and the nature of the disease (effects on fertility or mortality) all impact on the feedbacks that are critical to the evolution of resistance. By identifying relationships between CSS investment and the underlying epidemiological feedback for each mode of resistance in each framework, we distil complex feedbacks into simple combinations of selection pressures. When the parasite does not affect fertility, CSS investment reflects only the benefit of resistance and we explain why this is markedly different for innate and acquired resistance. If infection has no effect on host fertility, CSS investment in acquired immunity increases with the square of disease prevalence. While in contrast for evolving innate resistance, CSS investment is greatest at intermediate prevalence. When disease impacts fertility, only a fraction of the host population reproduce, and this introduces new ecological feedbacks to both the cost of resistance and the damage from infection. The multiple feedbacks in this case lead to the alternative result that the higher the abundance of infecteds, the higher the investment in innate resistance. A key insight is that maximal investment occurs at intermediate lifespans in a range of different host parasite interactions, but for disparate reasons which can only be understood by a detailed analysis of the feedbacks. We discuss the extension of our approach to structured host populations and parasite community dynamics. PMID- 26285918 TI - Initial dissolution kinetics of cocrystal of carbamazepine with nicotinamide. AB - OBJECTIVES: Objectives of this study are investigating the initial dissolution kinetics of the cocrystal of carbamazepine (CBZ) with nicotinamide (NIC) and understanding its initial dissolution process. METHODS: Cocrystal solids of CBZ with NIC were prepared by co-milling and solvent evaporation methods. The formation of cocrystal solid was verified via X-ray diffraction measurement. Dissolution tests of the solids were performed using an original flow cell and ultraviolet-visible spectroscopic detector. The spectra monitored in situ were analyzed to determine the dissolved compounds separately using the classical least squares regression method. The initial dissolution profiles were interpreted using simultaneous model of dissolution and phase changes. KEY FINDINGS: In the initial dissolution, CBZ in the cocrystal structure dissolved in water and it was suggested that CBZ reached a metastable intermediate state simultaneously with dissolution. The cocrystal solid prepared by solvent evaporation provided a higher rate constant of the phase change than that prepared by co-milling. Our results thus support the use of evaporation as the method of choice to produce ordered cocrystal structures. CONCLUSION: We suggest that CBZ forms dihydrate during the dissolution process; however, during the initial phase of dissolution, CBZ changes to a metastable intermediate phase. PMID- 26285919 TI - Association and gene-gene interactions study of reelin signaling pathway related genes with autism in the Han Chinese population. AB - Autism is a neurodevelopmental disorder with unclear etiology. Reelin had been proposed to participate in the etiology of autism due to its important role in brain development. The goal of this study was to explore the association and gene gene interactions of reelin signaling pathway related genes (RELN, VLDLR, LRP8, DAB1, FYN, and CDK5) with autism in Han Chinese population. Genotyping data of the six genes were obtained from a recent genome-wide association study performed in 430 autistic children who fulfilled the DSM-IV-TR criteria for autistic disorder, and 1,074 healthy controls. Single marker case-control association analysis and haplotype case-control association analysis were conducted after the data was screened. Multifactor dimensionality reduction (MDR) was applied to further test gene-gene interactions. Neither the single marker nor the haplotype association tests found any significant difference between the autistic group and the control group after permutation test of 1,000 rounds. The 4-locus MDR model (comprising rs6143734, rs1858782, rs634500, and rs1924267 which belong to RELN and DAB1) was determined to be the model with the highest cross-validation consistency (CVC) and testing balanced accuracy. The results indicate that an interaction between RELN and DAB1 may increase the risk of autism in the Han Chinese population. Furthermore, it can also be inferred that the involvement of RELN in the etiology of autism would occur through interaction with DAB1. PMID- 26285920 TI - IgM-type epidermolysis bullosa acquisita. PMID- 26285921 TI - Genetic damage in patients moving from hemodialysis to online hemodiafiltration. AB - End-stage renal failure patients exhibit a high incidence of genetic damage and genomic instability. Part of this genetic damage is assumed to be caused by the hemodialysis (HD) procedure. To reduce these effects, different alternative HD procedures have been proposed, such as the use of high efficiency convective therapies to improve the reactive oxygen species/antioxidant ratio. To determine the efficiency of online hemodiafiltration (HDF) technique on the levels of DNA damage, we have measured the frequency of micronucleus in peripheral blood lymphocytes of 33 individuals moving from low-flux HD to post-dilution online HDF. In addition to basal levels of genetic damage, potential changes in radiosensitivity were measured as indicators of genomic instability. Plasma antioxidant capacity was also determined. Second samples were obtained after 6 months on the HDF protocol. Results indicate that moving to online HDF therapy produce a significant reduction of the basal levels of genetic damage, but does not affect the genomic instability status. In addition, a greater increase in plasma antioxidant capacity was observed. In spite of the lack of correlation between these parameters, our results confirm the usefulness of the online HDF technique as a way to reduce DNA damage in HD patients. PMID- 26285923 TI - Retraction Note to: Construction of pancreatic cancer double-factor regulatory network based on chip data on the transcriptional level. PMID- 26285922 TI - The patient experience of sleep problems and their treatment in the context of current delusions and hallucinations. AB - OBJECTIVES: There is increasing recognition that sleep problems are common in patients with psychosis, that they exacerbate delusions and hallucinations and should be a treatment target. The aim of this study was to gain a patient perspective on the nature of sleep problems in psychosis and experience of treatment. DESIGN: A qualitative, semi-structured interview-based study to explore patient accounts of sleep problems and associated psychological treatment. METHODS: Ten patients with recent delusions and hallucinations, who had experienced sleep problems and received psychological treatment during a clinical trial (the Better Sleep Trial), were interviewed. Responses were analysed using interpretative phenomenological analysis. RESULTS: Patients reported experiencing problems of getting to sleep, staying asleep, too much sleep, nightmares, and erratic sleep patterns. These sleep problems caused emotional distress, fatigue, and reduction in daytime activities. Worry and psychotic experiences disturbed sleep, while consequent tiredness meant that patients coped poorly with voices and persecutory fears. Treatment for sleep problems was viewed very positively and considered to have wide-ranging impacts. CONCLUSIONS: Sleep disturbance is a major problem for patients with psychosis, which should be treated more often in services using evidence-based interventions. PRACTITIONER POINTS: Psychological interventions for sleep problems are valued by patients with psychosis. Patients with current distressing psychotic experiences report wide-ranging benefits from a brief psychological intervention for sleep problems. PMID- 26285924 TI - Retraction Note to: Correlations of SELE genetic polymorphisms with risk of coronary heart disease and myocardial infarction: a meta-analysis. PMID- 26285925 TI - Retraction Note to: SELP genetic polymorphisms may contribute to the pathogenesis of coronary heart disease and myocardial infarction: a meta-analysis. PMID- 26285926 TI - Retraction Note to: Role of RASSF1A promoter methylation in the pathogenesis of hepatocellular carcinoma: a meta-analysis of 21 cohort studies. PMID- 26285927 TI - Retraction Note to: Aberrant promoter methylation of RASSF1A gene may be correlated with colorectal carcinogenesis: a meta-analysis. PMID- 26285928 TI - Retraction Note to: Relationships of LDLR genetic polymorphisms with cerebral infarction: a meta-analysis. PMID- 26285929 TI - Retraction Note to: Genetic polymorphisms in VDR, ESR1 and ESR2 genes may contribute to susceptibility to Parkinson's disease: a meta-analysis. PMID- 26285930 TI - Retraction Note to: Role of p16 gene promoter methylation in gastric carcinogenesis: a meta-analysis. PMID- 26285931 TI - Retraction Note to: Correlations of SELE and SELP genetic polymorphisms with myocardial infarction risk: a meta-analysis and meta-regression. PMID- 26285932 TI - Retraction Note to: Uncovering the pathogenesis and identifying novel targets of pancreatic cancer using bioinformatics approach. PMID- 26285933 TI - Retraction Note to: Genetic polymorphisms in the CYP1A1 and CYP1B1 genes and susceptibility to bladder cancer: a meta-analysis. PMID- 26285934 TI - Retraction Note to: Lactoferrin promote primary rat osteoblast proliferation and differentiation via up-regulation of insulin-like growth factor-1 expression. PMID- 26285935 TI - Retraction Note to: Genetic variations in the KIR gene family may contribute to susceptibility to ankylosing spondylitis: a meta-analysis. PMID- 26285936 TI - Retraction Note to: Key genes associated with osteoporosis revealed by genome wide gene expression analysis. PMID- 26285937 TI - Retraction Note to: IL-18 genetic polymorphisms may contribute to the pathogenesis of tuberculosis among Asians: a meta-analysis of case-control studies. PMID- 26285938 TI - Retraction Note to: The role of cystatin C in vascular remodeling of balloon injured abdominal aorta of rabbits. PMID- 26285939 TI - Retraction Note to: Relationships between PON1 Q192R polymorphism and clinical outcome of antiplatelet treatment after percutaneous coronary intervention: a meta-analysis. PMID- 26285940 TI - Retraction Note to: ChIP-seq analysis of androgen receptor in LNCaP cell line. PMID- 26285941 TI - Retraction Note to: Identification of featured biomarkers in different types of lung cancer with DNA microarray. PMID- 26285942 TI - Retraction Note to: Meta-analysis of the relationship between single nucleotide polymorphism rs72689236 of caspase-3 and Kawasaki disease. PMID- 26285943 TI - Retraction Note to: Analyzing time-series microarray data reveals key genes in spinal cord injury. PMID- 26285945 TI - Retraction Note to: Text mining and network analysis of molecular interaction in non-small cell lung cancer by using natural language processing. PMID- 26285944 TI - Retraction Note to: LCK: a new biomarker candidate for the early diagnosis of acute myocardial infarction. PMID- 26285946 TI - Retraction Note to: Relationships of COX2 and MMP12 genetic polymorphisms with chronic obstructive pulmonary disease risk: a meta-analysis. PMID- 26285947 TI - Retraction Note to: Gene expression profiles on predicting protein interaction network and exploring of new treatments for lung cancer. PMID- 26285948 TI - Retraction Note to: An infectious molecular clone in early infection with HIV-1 subtype CRF01_AE strains: construction and biological properties. PMID- 26285949 TI - Retraction Note to: Knockdown of filaggrin influences the epidermal terminal differentiation via MAPK pathway in normal human epidermal keratinocytes. PMID- 26285950 TI - Retraction Note to: Distinctive pathways characterize A. actinomycetemcomitans and P. gingivalis. PMID- 26285953 TI - Language barriers leave us all in limbo. PMID- 26285951 TI - Glycemic Variability and Its Impact on Quality of Life in Adults With Type 1 Diabetes. AB - BACKGROUND: There is evidence suggesting that glycemic variability reduces quality of life (QoL) in people with type 2 diabetes, but this association has not been explored in type 1 diabetes. We aimed to assess whether glycemic variability has an impact on QoL in adults with established type 1 diabetes using multiple daily injections (MDI) of insulin or continuous subcutaneous insulin infusion (CSII). METHODS: Participants wore a blinded continuous glucose monitor for up to 5 days and completed the diabetes quality of life (DQOL) questionnaire. Glycemic variability measures were calculated using the EasyGV version 9.0 software. A correlation analysis was performed to assess whether there was a relationship between glycemic variability and measures of QoL. RESULTS: In all, 57 participants with type 1 diabetes (51% male, 65% on CSII, 35% on MDI, mean [SD] age 41 [13] years, duration of diabetes 21 [12] years, HbA1c 63 [12] mmol/mol [7.9% (1.1)], body mass index 25.2 [4.0] kg/m(2)) were included in the analysis. No significant associations between glycemic variability and DQOL total or subscale scores were demonstrated. The glycemic variability was significantly higher for MDI participants compared to CSII participants (P < .05 for all glycemic variability measures), but no significant difference in QoL between the 2 treatment modality groups was observed. CONCLUSIONS: Treatment with CSII is associated with lower glycemic variability compared to MDI. Despite this, and contrary to findings in type 2 diabetes, this study did not find an association between glycemic variability and QoL in adults with relatively well-controlled type 1 diabetes, irrespective of whether they are on MDI or CSII. PMID- 26285955 TI - Free gym sessions offered to help nurses unwind after long shifts. PMID- 26285952 TI - Impact of Blood Glucose Reporting on Glycemic Variability in Veterans With Diabetes. PMID- 26285954 TI - Better career pathway is high on RCN general secretary's to-do list. PMID- 26285956 TI - Steep increase in allegations of care home abuse. PMID- 26285957 TI - Action planned on undocumented migrant staff. PMID- 26285958 TI - Sitting at the bedside on ward rounds is best practice for patient experience. PMID- 26285959 TI - Diaries are late nurse's legacy. PMID- 26285960 TI - Union concern over 'undermining' of NHS Pay Review Body's remit. PMID- 26285961 TI - Nurses to advise inspection teams. PMID- 26285962 TI - Spray-based oxygen therapy effective in diabetic foot ulcers. PMID- 26285964 TI - A-level joy for future nursing student. PMID- 26285965 TI - Cuts in public health funding will hit areas of greater need hardest. PMID- 26285966 TI - New leader wants to inspire nurses to speak up for themselves. PMID- 26285972 TI - Obstructive sleep apnoea. PMID- 26285973 TI - Years of experience to bring to the bank. PMID- 26285974 TI - Keeping fit for purpose. PMID- 26285975 TI - A brave approach paid dividends. PMID- 26285982 TI - Men's Health Forum. PMID- 26285984 TI - MedScape. PMID- 26285986 TI - Calming music can relax patients and staff in the operating theatre. PMID- 26285987 TI - It all depends on who calls the tune in the operating team. PMID- 26285989 TI - NHS problems are fault of government, not nurses. PMID- 26285988 TI - RCN needs to balance union remit with professional roles. PMID- 26285990 TI - Do the maths to see impact of privatisation on patient care. PMID- 26285993 TI - Paul Dugdale. PMID- 26285994 TI - Evelyn Gillan. PMID- 26285996 TI - Advance care planning in dementia. AB - Advance care planning is the basis for delivering person-centred end of life care that accords with the wishes of the individual. It is important to support people with dementia in developing an advance care plan, since they may lose the capacity to make decisions associated with this early in the disease process. Healthcare policy indicates that we should all consider our wishes for end of life care. However, this may not be straightforward for people with dementia. This article considers the main issues in enabling advance care planning with people with dementia, reviews the limited evidence and offers possible solutions. PMID- 26285997 TI - Applying critical thinking to nursing. AB - Critical thinking and writing are skills that are not easy to acquire. The term 'critical' is used differently in social and clinical contexts. Nursing students need time to master the inquisitive and ruminative aspects of critical thinking that are required in academic environments. This article outlines what is meant by critical thinking in academic settings, in relation to both theory and reflective practice. It explains how the focus of a question affects the sort of critical thinking required and offers two taxonomies of learning, to which students can refer when analysing essay requirements. The article concludes with examples of analytical writing in reference to theory and reflective practice. PMID- 26285998 TI - Advance care planning. PMID- 26286001 TI - Working life on the ocean wave. PMID- 26285999 TI - Mind your attitude. PMID- 26286002 TI - Change for the better. PMID- 26286003 TI - Reality shock absorber. PMID- 26286004 TI - Patient dose evaluation for the whole-body low-dose multidetector CT (WBLDMDCT) skeleton study in multiple myeloma (MM). AB - OBJECTIVE: This study aimed at estimating the patient effective dose during whole body low-dose multi detector computed tomography with a scanner Philips Brillance 64, and to compare it with those reported in literature for the same procedure and with the dose of the conventional X-ray examination in our institution. MATERIALS AND METHODS: WBLDMDCT effective dose was evaluated for 29 MM patients, using Dose Length Product values. Conventional X-ray examination dose was estimated using a Rando Phantom and Dose Area Product indexes. ICRP Publication 103 based coefficients were used. RESULTS: Mean WBLDMDCT effective dose values estimated using sex-specific conversion coefficients and body weight factors-were 3.6 and 2.8 mSv for females and males, respectively. The effective dose for the conventional method was 1.2 mSv for Rando phantom. CONCLUSION: The WBLDMDCT effective dose in our institution is consistent with the values reported in previous studies. Such a dose is about 2.5- to 3-fold higher than the mean radiation dose of the conventional X-ray study. Nevertheless, considering the improved diagnostic accuracy of the CT investigation, the comfort of the patient and the old age of the MM population, dose/quality ratio can be considered favourable. PMID- 26286005 TI - Investigation of medical intervention with fatal outcome: the impact of post mortem CT and CT angiography. AB - Post-mortem computed tomography (PMCT) has been proven for its appropriateness to become an integral part of routine pre-autoptic forensic investigations either in the field of forensic investigation of fatal medical error or in hospital quality management. The autoptic investigation of unexpected and peri-interventional deaths can be usefully guided by post-mortem imaging which offers significant added value in the documentation of misplacement of medical devices before dissection with the risk of artificial relocation and the detection of iatrogenic air embolism. Post-mortem CT angiography (PMCTA) augments PMCT in the search for sources of hemorrhages and for the documentation of vascular patency and unimpaired perfusion after general and cardiovascular surgery or transvascular catheter-assisted interventions. Limitations of PMCT and PMCTA in medical error cases are method-related or time-dependent including artifacts by early post mortem tissue change. Thromboembolic complications including pulmonary embolism, the differentiation of ante- and post-mortem coagulation and the detection of myocardial infarction remain areas with compromised diagnostic efficiency as compared to autopsy. Furthermore, extended survival periods after a complication in question impedes visualization of contrast agent extravasation at vascular leakage sites. PMCT and PMCTA contribute substantially for proving a correct interventional approach and guide forensic or clinical autopsy in the reconstruction of adverse medical events with fatal outcome. Post-mortem imaging could also assume a new role as an alternative in a clinicopathological setting if autopsy is not achievable when the probability in the individual case is acceptable to answer specific questions. PMID- 26286006 TI - The role of contrast enhanced computed tomography in the diagnosis of necrotizing fasciitis and comparison with the laboratory risk indicator for necrotizing fasciitis (LRINEC). AB - PURPOSE: To evaluate the diagnostic efficacy of contrast enhanced computed tomography (CECT) in emergency departments for diagnosis of necrotizing fasciitis (NF) and for differential diagnosis of other musculoskeletal infections; to correlate radiological findings with the laboratory risk indicator for necrotizing fasciitis (LRINEC). MATERIALS AND METHODS: 7 radiological parameters to be analysed on CECT scans were established, exams of 36 patients with proven diagnosis of NF (n 12) and other musculoskeletal infections (n 24) were retrospectively reviewed; LRINEC score was calculated. Fisher's test and Spearman's and Kendall's coefficients of rank correlations were performed. RESULTS: Two parameters were found to be strongly associated with the diagnosis of NF: involvement of the fascia (Spearman's rho of 0.888, p < 0.001) and lack of fascial enhancement (Spearman's rho of 0.672, p < 0.001). LRINEC score did not show strong association with the presence of fasciitis NF (Spearman's rho of 0.490, p = 0.0024). CONCLUSION: Computed tomography (CT) parameters, which are significantly associated with the diagnosis of NF, are the involvement of the fascia and its lack of enhancement; LRINEC score could be high (>5) also in other musculoskeletal infections. Final diagnosis of necrosis among the fascia is surgical. Presence of gas is not a specific sign of necrotizing fasciitis being present in other musculoskeletal infections. CT could easily discriminate NF from other musculoskeletal infections, adds an important value to clinical and laboratory tests in diagnosis of NF in an emergency context when magnetic resonance imaging, which is superior to CT in this discernment, could not be performed. PMID- 26286007 TI - Implying Analytic Measures for Unravelling Rheumatoid Arthritis Significant Proteins Through Drug-Target Interaction. AB - Rheumatoid arthritis (RA) is a systemic autoimmune and inflammatory disease that mainly alters the synovial joints and ultimately leads to their destruction. The involvement of the immune system and its related cells is a basic trademark of autoimmune-associated diseases. The present work focuses on network analysis and its functional characterization to predict novel targets for RA. The interactive model called as rheumatoid arthritis drug-target-protein (RA-DTP) is built of 1727 nodes and 7954 edges followed the power-law distribution. RA-DTP comprised of 20 islands, 55 modules and 123 submodules. Good interactome coverage of target protein was detected in island 2 (Q-Score 0.875) which includes 673 molecules with 20 modules and 68 submodules. The biological landscape of these modules was examined based on the participation molecules in specific cellular localization, molecular function and biological pathway with favourable p value. Functional characterization and pathway analysis through KEGG, Biocarta and Reactome also showed their involvement in relation to the immune system and inflammatory processes and biological processes such as cell signalling and communication, glucosamine metabolic process, renin-angiotensin system, BCR signals, galactose metabolism, MAPK signalling, complement and coagulation system and NGF signalling pathways. Traffic values and centrality parameters were applied as the selection criteria for identifying potential targets from the important hubs which resulted into FOS, KNG1, PTGDS, HSP90AA1, REN, POMC, FCER1G, IL6, ICAM1, SGK1, NOS3 and PLA2G4A. This approach provides an insight into experimental validation of these associations of potential targets for clinical value to find their effect on animal studies. PMID- 26286008 TI - Flavonoids as Multi-target Inhibitors for Proteins Associated with Ebola Virus: In Silico Discovery Using Virtual Screening and Molecular Docking Studies. AB - Ebola virus is a single-stranded, negative-sense RNA virus that causes severe hemorrhagic fever in humans and non-human primates. This virus is unreceptive to a large portion of the known antiviral drugs, and there is no valid treatment as on date for disease created by this pathogen. Looking into its ability to create a pandemic scenario across globe, there is an utmost need for new drugs and therapy to combat this life-threatening infection. The current study deals with the evaluation of the inhibitory activity of flavonoids against the four selected Ebola virus receptor proteins, using in silico studies. The viral proteins VP40, VP35, VP30 and VP24 were docked with small molecules obtained from flavonoid class and its derivatives and evaluated on the basis of energetics, stereochemical considerations and pharmacokinetic properties to identify potential lead compounds. The results showed that both top-ranking screened flavonoids, i.e., Gossypetin and Taxifolin, showed better docking scores and binding energies in all the EBOV receptors when compared to those of the reported compound. All the screened flavonoids have known antiviral activity, acceptable pharmacokinetic properties and are being used on human and thus can be taken as anti-Ebola therapy without the time lag for clinical trial. PMID- 26286009 TI - Investigating the Conformational Structure and Potential Site Interactions of SOD Inhibitors on Ec-SOD in Marine Mud Crab Scylla serrata: A Molecular Modeling Approach. AB - Superoxide dismutases (SODs) act as a first line of the enzymatic antioxidant defense system to control cellular superoxide anion toxicity. Previously, several inhibitors have been widely identified and catalogued for inhibition of SOD activity; however, still the information about the mechanism of interaction and points toward the inhibitor interactions in structures of SODs in general and in extracellular (Ec)-SOD in particular is still in naive. In the present research, we present an insight to elucidate the molecular basis of interactions of SOD inhibitors with Ec-SOD in mud crab Scylla serrata using molecular modeling and docking approaches. Different inhibitors of SOD such as hydrogen peroxide [Formula: see text], potassium cyanide, sodium dodecyl sulfate (SDS), [Formula: see text]-mercaptoethanol and dithiocarbamate were screened to understand the potential sites that may act as sites for cleavage or blocking in the protein. SOD-SDS and [Formula: see text] complex interactions indicate residues Pro72 and Asp102 of the predicted crab Ec-SOD as common targets. The GOLD result indicates that Pro72, Asp102 and Thr103 are commonly acting as the site of interaction in Ec-SOD of S. serrata with SOD inhibitors. For the first time, the results of this study provide an insight into the structural properties of Ec-SOD of S. serrata and define the possible involvements between the amino acids present in its active sites, i.e., in the regions from 70 to 84 and from 101 to 103 and different inhibitors. PMID- 26286010 TI - Identify Secretory Protein of Malaria Parasite with Modified Quadratic Discriminant Algorithm and Amino Acid Composition. AB - Malaria parasite secretes various proteins in infected red blood cell for its growth and survival. Thus identification of these secretory proteins is important for developing vaccine or drug against malaria. In this study, the modified method of quadratic discriminant analysis is presented for predicting the secretory proteins. Firstly, 20 amino acids are divided into five types according to the physical and chemical characteristics of amino acids. Then, we used five types of amino acids compositions as inputs of the modified quadratic discriminant algorithm. Finally, the best prediction performance is obtained by using 20 amino acid compositions, the sensitivity of 96 %, the specificity of 92 % with 0.88 of Mathew's correlation coefficient in fivefold cross-validation test. The results are also compared with those of existing prediction methods. The compared results shown our method are prominent in the prediction of secretory proteins. PMID- 26286011 TI - Probing the impact of temperature on molecular events in a developmental system. AB - A well-appreciated general feature of development is the ability to achieve a normal outcome despite the inevitable variability at molecular, genetic, or environmental levels. But it is not well understood how changes in a global factor such as temperature bring about specific challenges to a developmental system in molecular terms. Here we address this question using early Drosophila embryos where the maternal gradient Bicoid (Bcd) instructs anterior-patterning (AP) patterning. We show that temperature can impact the amplitude of the Bcd gradient in the embryo. To evaluate how molecular decisions are made at different temperatures, we quantify Bcd concentrations and the expression of its target gene hunchback (hb) in individual embryos. Our results suggest a relatively robust Bcd concentration threshold in inducing hb transcription within a temperature range. Our results also reveal a complex nature of the effects of temperature on the progressions of developmental and molecular events of the embryo. Our study thus advances the concept of developmental robustness by quantitatively elaborating specific features and challenges-imposed by changes in temperature-that an embryo must resolve. PMID- 26286012 TI - Application of carbon nanoparticles to mark locations for re-inspection after colonic polypectomy. AB - BACKGROUND: Endoscopic surgery has been a novel treatment for colon polyps or even early colorectal cancer. However, the exact re-inspection after colonic polypectomy to detect the scar from polyp removal was difficult to be performed. In our previous study, colon cancer tattooed with carbon nanoparticles was easily found during surgery. We speculated that carbon nanoparticles could be used in exact re-inspection after colonic polypectomy. OBJECTIVE: To evaluate the efficiency of carbon nanoparticles for re-inspection after colonic polypectomy. METHODS: Twenty-four patients with precancerous lesion or early colorectal cancer that underwent colonoscopic polypectomy between October 2012 and December 2013 were enrolled in the study. Participants were divided into two groups. Group A patients were injected with carbon nanoparticles beneath the lesion sites 3 cm. Group B patients were not treated with nanoparticles. All patients underwent quarterly colonoscopies. Once the colonoscope was withdrawn from the site last time record, the time spent searching for lesions was recorded. RESULTS: There were no significant differences between general conditions or lesion pathology between the groups. The time spent searching for lesions in Group B was much longer than that in Group A (13.67 +/- 8.07 vs. 1.21 +/- 0.39 min, P < 0.001). Carbon nanoparticles marked lesions for 12 months in some patients, and no adverse reactions were reported. LIMITATIONS: It was a small sample study. CONCLUSIONS: Tattooing lesions using carbon nanoparticles suspensions is safe. The durability of dye enables lesions to be re-checked by colonoscopy or laparoscopy for up to 1 year. PMID- 26286013 TI - Laparoscopy decreases complications for obese patients undergoing elective rectal surgery. AB - INTRODUCTION: While there are many reported advantages to laparoscopic surgery compared to open surgery, the impact of a laparoscopic approach on postoperative morbidity in obese patients undergoing rectal surgery has not been studied. Our goal was to determine whether obese patients undergoing laparoscopic rectal surgery experienced the same benefits as non-obese patients. METHODS: We identified patients undergoing rectal resections using the National Surgical Quality Improvement Project Participant Use Data File. We performed multivariable analyses to determine the independent association between laparoscopy and postoperative complications. RESULTS: A total of 26,437 patients underwent rectal resection. The mean age was 58.5 years, 32.6 % were obese, and 47.2 % had cancer. Laparoscopic procedures were slightly less common in obese patients compared to non-obese patients (36.0 vs. 38.2 %, p = 0.0006). In unadjusted analyses, complications were lower with the laparoscopic approach in both obese (18.9 vs. 32.4 %, p < 0.0001) and non-obese (15.6 vs. 25.3 %, p < 0.0001) patients. In a multivariable analysis controlling for potential confounders, the risk of postoperative complications increased as the degree of obesity worsened. The likelihood of experiencing a postoperative complication increased by 25, 45, and 75 % for obese class I, obese class II, and obese class III patients, respectively. A laparoscopic approach was associated with a 40 % decreased odds of a postoperative complication for all patients (OR 0.60, 95 % CI 0.56-0.64). CONCLUSION: Laparoscopic rectal surgery is associated with fewer complications when compared to open rectal surgery in both obese and non-obese patients. Obesity was an independent risk factor for postoperative complications. In appropriately selected patients, rectal surgery outcomes may be improved with a minimally invasive approach. PMID- 26286014 TI - Who Needs Follow-Up after Endoscopic Resection of Colorectal Adenomas? AB - BACKGROUND: Surveillance colonoscopy after endoscopic resection of colorectal adenomas is a crucial step in the concept of colorectal cancer screening. After identifying the patients at risk with screening and resection of adenomas, there has to be a tailored surveillance. Surveillance colonoscopy should detect recurrent and metachronal adenomas at a stage where they can be removed endoscopically. In the following, the criteria for a risk-adapted surveillance interval are presented. METHODS: A literature review based on American, European, and German guidelines for surveillance after polypectomy and the German guideline for the diagnosis and treatment of ulcerative colitis, as well as a selective literature search into hereditary colorectal cancer were performed. RESULTS: State of the art surveillance after endoscopic resection of colorectal adenomas is based on a focused anamnesis and the index colonoscopy. On the basis of existing guidelines, a risk-adapted surveillance strategy can be implemented. CONCLUSIONS: Adherence to surveillance guidelines is a basic part of colorectal cancer screening and should be the starting point for further research. PMID- 26286015 TI - Effect of Short-Term Mobile Phone Base Station Exposure on Cognitive Performance, Body Temperature, Heart Rate and Blood Pressure of Malaysians. AB - Individuals who report their sensitivity to electromagnetic fields often undergo cognitive impairments that they believe are due to the exposure of mobile phone technology. The aim of this study is to clarify whether short-term exposure at 1 V/m to the typical Global System for Mobile Communication and Universal Mobile Telecommunications System (UMTS) affects cognitive performance and physiological parameters (body temperature, blood pressure and heart rate). This study applies counterbalanced randomizing single blind tests to determine if sensitive individuals experience more negative health effects when they are exposed to base station signals compared with sham (control) individuals. The sample size is 200 subjects with 50.0% Idiopathic Environmental Intolerance attributed to electromagnetic fields (IEI-EMF) also known as sensitive and 50.0% (non-IEI-EMF). The computer-administered Cambridge Neuropsychological Test Automated Battery (CANTAB eclipse(TM)) is used to examine cognitive performance. Four tests are chosen to evaluate Cognitive performance in CANTAB: Reaction Time (RTI), Rapid Visual Processing (RVP), Paired Associates Learning (PAL) and Spatial Span (SSP). Paired sample t-test on the other hand, is used to examine the physiological parameters. Generally, in both groups, there is no statistical significant difference between the exposure and sham exposure towards cognitive performance and physiological effects (P's > 0.05). PMID- 26286016 TI - Blocking the tropomyosin receptor kinase A (TrkA) receptor inhibits pain behaviour in two rat models of osteoarthritis. AB - OBJECTIVES: Tropomyosin receptor kinase A (TrkA) mediates nociceptor sensitisation by nerve growth factor (NGF), but it is unknown whether selective TrkA inhibition will be an effective strategy for treating osteoarthritis (OA) pain. We determined the effects of a TrkA inhibitor (AR786) on pain behaviour, synovitis and joint pathology in two rat OA models. METHODS: Knee OA was induced in rats by intra-articular monosodium-iodoacetate (MIA) injection or meniscal transection (MNX) and compared with saline-injected or sham-operated controls. Pain behaviour was assessed as weight-bearing asymmetry and paw withdrawal threshold to punctate stimulation. Oral doses (30 mg/kg) of AR786 or vehicle were administered twice daily in either preventive (day -1 to -27) or treatment (day 14-28) protocols. Effect maintenance was evaluated for 2 weeks after treatment discontinuation. Alterations in knee structure (cartilage, subchondral bone and synovium) were examined by macroscopic visualisation of articular surfaces and histopathology. RESULTS: Preventive AR786 treatment inhibited pain behaviour development and therapeutic treatment attenuated established pain behaviour. Weight-bearing asymmetry increased 1 week after treatment discontinuation, but remained less than in vehicle-treated arthritic rats, whereas paw withdrawal thresholds returned to levels of untreated rats within 5 days of treatment discontinuation. AR786 treatment reduced MIA-induced synovitis and did not significantly affect osteochondral pathology in either model. CONCLUSIONS: Blocking NGF activity by inhibiting TrkA reduced pain behaviour in two rat models of OA. Analgesia was observed both using preventive and treatment protocols, and was sustained after treatment discontinuation. Selective inhibitors of TrkA therefore hold potential for OA pain relief. PMID- 26286017 TI - Outcomes of percutaneous coronary intervention in patients with rheumatoid arthritis and systemic lupus erythematosus: an 11-year nationwide cohort study. AB - OBJECTIVES: Patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have an increased risk of developing coronary atherosclerosis. However, the impact of RA and SLE on the outcomes in patients undergoing percutaneous coronary intervention (PCI) remains largely underdetermined. METHODS: Using the National Health Insurance Research Database of Taiwan, we identified 171 547 adult patients who underwent first-time PCI between 2000 and 2010. Among these patients, 525 had established RA, and 211 had SLE. The ORs of inhospital mortality and HRs of overall mortality and adverse cardiac outcomes after PCI (ie, ischaemic events, repeat revascularisation and major adverse cardiac events (MACE)) in relation to RA and SLE were estimated. RESULTS: After adjustment for potential confounders, including patient characteristics and procedural variables, RA (OR=1.73, 95% CI 1.11 to 2.68) and SLE (OR=3.81, 95% CI 2.02 to 7.16) were independent predictors of inhospital mortality. In addition, RA was independently associated with overall mortality (HR=1.55, 95% CI 1.35 to 1.79), ischaemic events (HR=1.18, 95% CI 1.01 to 1.39) and MACE (HR=1.20, 95% CI 1.07 to 1.34) during long-term follow-up, whereas SLE was independently associated with overall mortality (HR=2.20, 95% CI 1.74 to 2.78), repeat revascularisation (HR=1.27, 95% CI 1.02 to 1.58) and MACE (HR=1.47, 95% CI 1.24 to 1.75). Compared with patients without autoimmune diseases, patients with more recent SLE-related hospitalisations prior to PCI were at higher risk of inhospital mortality (p for trend <0.0001). CONCLUSIONS: This study recognises the inherent risks associated with RA and SLE in patients undergoing PCI and highlights the necessity to improve the caring and secondary prevention strategies for these high-risk patients. PMID- 26286018 TI - Patients with chronic back pain of short duration from the SPACE cohort: which MRI structural lesions in the sacroiliac joints and inflammatory and structural lesions in the spine are most specific for axial spondyloarthritis? AB - OBJECTIVES: To investigate the extent and performance of MRI lesions in the sacroiliac joint (MRI-SI) and spine (MRI-spine) in patients with suspected axial spondyloarthritis (axSpA). METHODS: MRI-SI/spine of patients with chronic back pain (onset <45 years) in the SPondyloArthritis Caught Early (SPACE) cohort were scored by two well-trained readers for inflammation, fatty lesions, erosions, sclerosis/ankylosis and syndesmophytes. MRI performances were tested against the Assessment of Spondyloarthritis international Society (ASAS) axSpA criteria (positive: imaging-arm+ or clinical-arm+; negative: possible axSpA (few spondyloarthritis (SpA) features present) or no SpA). Arbitrary cut-off levels for MRI lesions were set to assure at least 95% specificity (tested in the no SpA group). RESULTS: In total 126 patients were ASAS criteria positive (73 imaging arm+ (22 by modified New York criteria (mNY)+; 51 by MRI+mNY-); 53 clinical-arm+) and 161 were ASAS criteria negative (89 possible axSpA and 72 no SpA). On MRI-SI (n=287), at least three fatty lesions (or at least three erosions) were seen in 45.5 (63.6)% of mNY+ patients, 15.7 (47.1)% of MRI+mNY- patients and 15.1 (13.2)% of clinical-arm+ patients versus 3.4 (6.7)% of possible axSpA patients and 2.8 (4.2)% of no SpA patients. A combined rule (at least five fatty lesions and/or erosions) performed equally well. Sclerosis and ankylosis were too rare to analyse. On MRI-spine (n=284), at least five inflammatory lesions (or at least five fatty lesions) were seen in 27.3 (18.2)% of mNY+ patients, 13.7 (21.6)% of MRI+mNY- patients and 3.8 (1.9)% of clinical-arm+ patients versus 4.5 (6.7)% of possible SpA patients and 2.9 (4.3)% of no SpA patients. CONCLUSIONS: The presence of (1) at least five fatty lesions and/or erosions on MRI-SI, (2) at least five inflammatory lesions or (3) at least five fatty lesions on MRI-spine allows an acceptable discrimination of axSpA and no SpA, while assuring >95% specificity. PMID- 26286019 TI - Chiral Cyclobutane beta-Amino Acid-Based Amphiphiles: Influence of Cis/Trans Stereochemistry on Solution Self-Aggregation and Recognition. AB - Novel diastereomeric anionic amphiphiles based on the rigid cyclobutane beta amino acid scaffold have been synthesized and deeply investigated with the aim of generating new functional supramolecular architectures on the basis of the rational design of original amphiphilic molecules and the control of their self assembly. The main interest has been focused on the effect that cis/trans stereochemistry exerts on their molecular organization and recognition. In diluted solutions, the relative stereochemistry mainly influences the headgroup solvation and anionic-charge stabilization, i.e., better stabilized in the cis diastereoisomer due to intramolecular hydrogen-bonding and/or charge-dipole interactions. This provokes differences in their physicochemical behavior (pKa, cmc, conductivity) as well as in the structural parameters of the spherical micelles formed. Although both diastereoisomers form fibers that evolve with time from the spherical micelles, they display markedly different morphology and kinetics of formation. In the lyotropic liquid crystal domain, the greatest differences are observed at the highest concentrations and can be ascribed to different hydrogen-bonding and molecular packing imposed by the stereochemical constraints. Remarkably, the spherical micelles of the two anionic surfactants show dramatically diverse enantioselection ability for bilirubin enantiomers. In addition, both the surfactants form heteroaggregates with bilirubin at submicellar concentrations but with a different expression of supramolecular chirality. This points out that the unlike relative configuration of the two surfactants influences their chiral recognition ability as well as the fashion in which chirality is expressed at the supramolecular level by controlling the molecular organization in both micellar aggregates and surfactant/bilirubin heteroaggregates. All these differential features can be appropriate and useful for the design and development of new soft materials with predictable and tunable properties and reveal the cyclobutane motif as a valuable scaffold for the preparation of new amphiphiles. PMID- 26286022 TI - Hexacene: Synthesis, Properties and Future Perspectives. PMID- 26286021 TI - Caesarean delivery and the risk of offspring overweight and obesity over the life course: a systematic review and bias-adjusted meta-analysis. AB - A causal role of Caesarean delivery (CD) on developing overweight and obesity in the life course of offspring has been postulated. However, the true strength of this association is not clear and the potential for confounding has not been adequately addressed. A systematic review and meta-analysis were conducted to evaluate the strength of this association, this time using a bias-adjusted model in addition to conventional methods. Our search yielded 32 estimates from 14 publications (n = 261,000) for meta-analysis. The pooled analysis of seven estimates (n = 194,463) demonstrated a trend only towards a risk increase (RR = 1.15; 95% CI:0.94, 1.40) in overweight and obesity combined (ow+ob) due to CD in early childhood (0-5 years) and a similar trend was observed for mid-childhood and adolescence (5-18 years). In adulthood, a moderate increase in risk for ow+ob due to CD was observed (n = 30,200) (RR = 1.28; 95% CI 1.02, 1.34). Results for obesity and overweight separately were stronger for obesity and demonstrated a decreasing effect across the three life stages. Conventional methods of analysis suggested less uncertainty than we report and publication bias assessment was strongly suggestive of a bias in favour of positive studies. The current analysis therefore suggests that the small effects seen with CD in this and previous meta analyses are probably a cumulative consequence of several biases we have outlined, including confounding effect and publication bias. PMID- 26286020 TI - Assessing the genetic diversity of Cu resistance in mine tailings through high throughput recovery of full-length copA genes. AB - Characterizing the genetic diversity of microbial copper (Cu) resistance at the community level remains challenging, mainly due to the polymorphism of the core functional gene copA. In this study, a local BLASTN method using a copA database built in this study was developed to recover full-length putative copA sequences from an assembled tailings metagenome; these sequences were then screened for potentially functioning CopA using conserved metal-binding motifs, inferred by evolutionary trace analysis of CopA sequences from known Cu resistant microorganisms. In total, 99 putative copA sequences were recovered from the tailings metagenome, out of which 70 were found with high potential to be functioning in Cu resistance. Phylogenetic analysis of selected copA sequences detected in the tailings metagenome showed that topology of the copA phylogeny is largely congruent with that of the 16S-based phylogeny of the tailings microbial community obtained in our previous study, indicating that the development of copA diversity in the tailings might be mainly through vertical descent with few lateral gene transfer events. The method established here can be used to explore copA (and potentially other metal resistance genes) diversity in any metagenome and has the potential to exhaust the full-length gene sequences for downstream analyses. PMID- 26286023 TI - Stromal cell-derived factor 2 is critical for Hsp90-dependent eNOS activation. AB - Endothelial nitric oxide synthase (eNOS) catalyzes the conversion of l-arginine and molecular oxygen into l-citrulline and nitric oxide (NO), a gaseous second messenger that influences cardiovascular physiology and disease. Several mechanisms regulate eNOS activity and function, including phosphorylation at Ser and Thr residues and protein-protein interactions. Combining a tandem affinity purification approach and mass spectrometry, we identified stromal cell-derived factor 2 (SDF2) as a component of the eNOS macromolecular complex in endothelial cells. SDF2 knockdown impaired agonist-stimulated NO synthesis and decreased the phosphorylation of eNOS at Ser(1177), a key event required for maximal activation of eNOS. Conversely, SDF2 overexpression dose-dependently increased NO synthesis through a mechanism involving Akt and calcium (induced with ionomycin), which increased the phosphorylation of Ser(1177) in eNOS. NO synthesis by iNOS (inducible NOS) and nNOS (neuronal NOS) was also enhanced upon SDF2 overexpression. We found that SDF2 was a client protein of the chaperone protein Hsp90, interacting preferentially with the M domain of Hsp90, which is the same domain that binds to eNOS. In endothelial cells exposed to vascular endothelial growth factor (VEGF), SDF2 was required for the binding of Hsp90 and calmodulin to eNOS, resulting in eNOS phosphorylation and activation. Thus, our data describe a function for SDF2 as a component of the Hsp90-eNOS complex that is critical for signal transduction in endothelial cells. PMID- 26286024 TI - The transcription cofactor c-JUN mediates phenotype switching and BRAF inhibitor resistance in melanoma. AB - Most patients with BRAF-mutant metastatic melanoma display remarkable but incomplete and short-lived responses to inhibitors of the BRAF kinase or the mitogen-activated protein kinase kinase (MEK), collectively BRAF/MEK inhibitors. We found that inherent resistance to these agents in BRAF(V600)-mutant melanoma cell lines was associated with high abundance of c-JUN and characteristics of a mesenchymal-like phenotype. Early drug adaptation in drug-sensitive cell lines grown in culture or as xenografts, and in patient samples during therapy, was consistently characterized by down-regulation of SPROUTY4 (a negative feedback regulator of receptor tyrosine kinases and the BRAF-MEK signaling pathway), increased expression of JUN and reduced expression of LEF1. This coincided with a switch in phenotype that resembled an epithelial-mesenchymal transition (EMT). In cultured cells, these BRAF inhibitor-induced changes were reversed upon removal of the drug. Knockdown of SPROUTY4 was sufficient to increase the abundance of c JUN in the absence of drug treatment. Overexpressing c-JUN in drug-naive melanoma cells induced similar EMT-like phenotypic changes to BRAF inhibitor treatment, whereas knocking down JUN abrogated the BRAF inhibitor-induced early adaptive changes associated with resistance and enhanced cell death. Combining the BRAF inhibitor with an inhibitor of c-JUN amino-terminal kinase (JNK) reduced c-JUN phosphorylation, decreased cell migration, and increased cell death in melanoma cells. Gene expression data from a panel of melanoma cell lines and a patient cohort showed that JUN expression correlated with a mesenchymal gene signature, implicating c-JUN as a key mediator of the mesenchymal-like phenotype associated with drug resistance. PMID- 26286025 TI - Intravascular pressure enhances the abundance of functional Kv1.5 channels at the surface of arterial smooth muscle cells. AB - Voltage-dependent potassium (K(v)) channels are present in various cell types, including smooth muscle cells (myocytes) of resistance-sized arteries that control systemic blood pressure and regional organ blood flow. Intravascular pressure depolarizes arterial myocytes, stimulating calcium (Ca(2+)) influx through voltage-dependent Ca(2+) (Ca(v)) channels that results in vasoconstriction and also K(+) efflux through K(v) channels that oppose vasoconstriction. We hypothesized that pressure-induced depolarization may not only increase the open probability of plasma membrane-resident K(v) channels but also increase the abundance of these channels at the surface of arterial myocytes to limit vasoconstriction. We found that K(v)1.5 and K(v)2.1 proteins were abundant in the myocytes of resistance-sized mesenteric arteries. K(v)1.5, but not K(v)2.1, continuously recycled between the intracellular compartment and the plasma membrane in contractile arterial myocytes. Using ex vivo preparations of intact arteries, we showed that physiological intravascular pressure through membrane depolarization or membrane depolarization in the absence of pressure inhibited the degradation of internalized K(v)1.5 and increased recycling of K(v)1.5 to the plasma membrane. Accordingly, by stimulating the activity of Ca(v)1.2, membrane depolarization increased whole-cell K(v)1.5 current density in myocytes and K(v)1.5 channel activity in pressurized arteries. In contrast, the total amount and cell surface abundance of K(v)2.1 were independent of intravascular pressure or membrane potential. Thus, our data indicate that intravascular pressure-induced membrane depolarization selectively increased K(v)1.5 surface abundance to increase K(v) currents in arterial myocytes, which would limit vasoconstriction. PMID- 26286026 TI - Determining effects of areca (betel) nut chewing in a prospective cohort of pregnant women in Madang Province, Papua New Guinea. AB - BACKGROUND: Chewing areca nut (AN), also known as betel nut, is common in Asia and the South Pacific and the habit has been linked to a number of serious health problems including oral cancer. Use of AN in pregnancy has been associated with a reduction in mean birthweight in some studies, but this association and the relationship between AN chewing and other adverse pregnancy outcomes remain poorly understood. METHODS: We assessed the impact of AN chewing on adverse outcomes including stillbirth, low birthweight (LBW, <2,500 g) and anaemia at delivery (haemoglobin <11.0 g/dL) in a longitudinal cohort of 2,700 pregnant women residing in rural lowland Papua New Guinea (PNG) from November 2009 until February 2013. Chewing habits and participant characteristics were evaluated at first antenatal visit and women were followed until delivery. RESULTS: 83.3% [2249/2700] of pregnant women used AN, and most chewed on a daily basis (86.2% [1939/2249]. Smoking and alcohol use was reported by 18.9% (511/2700) and 5.0% (135/2688) of women, respectively. AN use was not associated with pregnancy loss or congenital abnormalities amongst women with a known pregnancy outcome (n = 2215). Analysis of 1769 birthweights did not demonstrate an association between AN and LBW (chewers: 13.7% [200/1459] vs. non-chewers: 14.5% [45/310], P = 0.87) or reduced mean birthweight (2957 g vs. 2966 g; P = 0.76). Women using AN were more likely to be anaemic (haemoglobin <11 g/dL) at delivery (75.2% [998/1314] vs. 63.9% [182/285], adjusted odds ratio [95% CI]: 1.67 [1.27, 2.20], P < 0.001). Chewers more commonly had male babies than non-chewers (46.1% [670/1455] vs. 39.8% [123/309], P = 0.045). CONCLUSIONS: AN chewing may contribute to anaemia. Although not associated with other adverse pregnancy outcome in this cohort gestational AN use should be discouraged, given the potential adverse effects on haemoglobin and well-established long-term health risk including oral cancer. Future research evaluating the potential association of AN use and anaemia may be warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT01136850 (06 April 2010). PMID- 26286028 TI - Current trends in the use of cardiac implantable electronic devices and interventional electrophysiological procedures in the European Society of Cardiology member countries: 2015 report from the European Heart Rhythm Association. AB - AIMS: The aim was to provide comprehensive information on the use of cardiac implantable electronic device (CIED) and catheter ablation therapy in the European Society of Cardiology (ESC) area. METHODS AND RESULTS: The European Heart Rhythm Association (EHRA) has collected data on use of invasive arrhythmia managements since 2008. Fifty-one of the 56 ESC member countries provided data for the EHRA White Book 2015. This analysis is based on the current and previous editions of the EHRA White Book. Up-to-date information on procedure rates for the last 5 years together with information on economic resources, reimbursement systems, and training requirements are presented for each country and the five geographical ESC regions. In 2014, the CIED implantation rates per million population were highest in the Western followed by the Southern and Northern European countries. The catheter ablation activity was largest in the Western followed by the Northern and Southern areas. Altogether the procedure rates were lowest in the Eastern European and in the non-European ESC countries. In the European ESC countries, the procedure rates were 3-10 times higher than in the non-European ESC countries. However, in some countries with a relatively low gross domestic product the procedure rates exceeded the average values indicating that utilization of arrhythmia therapies was not driven merely by the economic factors. CONCLUSION: This analysis indicates that considerable heterogeneity in the availability and utilization of arrhythmia therapies still exist across the ESC area. The data will hopefully aid in directing future activities and promote harmonization of cardiac arrhythmia care in the ESC countries. PMID- 26286027 TI - Positive association of tomato consumption with serum urate: support for tomato consumption as an anecdotal trigger of gout flares. AB - BACKGROUND: Gout is a consequence of an innate immune reaction to monosodium urate crystals deposited in joints. Acute gout attacks can be triggered by dietary factors that are themselves associated with serum urate levels. Tomato consumption is an anecdotal trigger of gout flares. This study aimed to measure the frequency of tomato consumption as a self-reported trigger of gout attacks in a large New Zealand sample set, and to test the hypothesis that tomato consumption is associated with serum urate levels. METHODS: Two thousand fifty one New Zealanders (of Maori, Pacific Island, European or other ancestry) with clinically-ascertained gout were asked about gout trigger foods. European individuals from the Atherosclerosis Risk In Communities (ARIC; n = 7517) Study, Cardiovascular Health Study (CHS; n = 2151) and Framingham Heart Study (FHS; n = 3052) were used to test, in multivariate-adjusted analyses, for association between serum urate and tomato intake. RESULTS: Seventy one percent of people with gout reported having >=1 gout trigger food. Of these 20% specifically mentioned tomatoes, the 4(th) most commonly reported trigger food. There was association between tomato intake and serum urate levels in the ARIC, CHS and FHS combined cohort (beta = 0.66 MUmolL(-1) increase in serum urate per additional serve per week; P = 0.006) - evident in both sexes (men: beta = 0.84 MUmolL(-1), P = 0.035; women: beta = 0.59 MUmolL (-1), P = 0.041). CONCLUSIONS: While our descriptive and observational data are unable to support the claim that tomato consumption is a trigger of gout attacks, the positive association between tomato consumption and serum urate levels suggests that the self-reporting of tomatoes as a dietary trigger by people with gout has a biological basis. PMID- 26286029 TI - VE-821, an ATR inhibitor, causes radiosensitization in human tumor cells irradiated with high LET radiation. AB - BACKGROUND: High linear energy transfer (LET) radiation such as carbon ion particles is successfully used for treatment of solid tumors. The reason why high LET radiation accomplishes greater tumor-killing than X-rays is still not completely understood. One factor would be the clustered or complex-type DNA damages. We previously reported that complex DNA double-strand breaks produced by high LET radiation enhanced DNA end resection, and this could lead to higher kinase activity of ATR protein recruited to RPA-coated single-stranded DNA. Although the effect of ATR inhibition on cells exposed to low LET gamma-rays has recently been reported, little is known regarding the effect of ATR inhibitor on cells treated with high LET radiation. The purpose of this study is to investigate the effects of the ATR inhibitor VE-821 in human tumor and normal cells irradiated with high LET carbon ions. FINDINGS: HeLa, U2OS, and 1BR-hTERT (normal) cells were pre-treated with 1 MUM VE-821 for 1 hour and irradiated with either high LET carbon ions or X-rays. Cell survival, cell cycle distribution, cell growth, and micronuclei formation were evaluated. VE-821 caused abrogation of G2/M checkpoint and forced irradiated cells to divide into daughter cells. We also found that carbon ions caused a higher number of multiple micronuclei than X rays, leading to decreased cell survival in tumor cells when treated with VE-821, while the survival of irradiated normal cells were not significantly affected by this inhibitor. CONCLUSIONS: ATR inhibitor would be an effective tumor radiosensitizer with carbon ion irradiation. PMID- 26286030 TI - Food-Nonfood Discrimination in Ancestral Vertebrates: Gamete Cannibalism and the Origin of the Adaptive Immune System. AB - Adaptive immunity is a complex system that appeared twice in vertebrates (in gnathostomes and in jawless fish) although it is not required for invertebrate defence. The adaptive immune system is tightly associated with self-non-self discrimination, and it is now clear that this interplay is not limited to the prevention of autoreactivity. Micro-organisms are usually considered for their pathogenicity or symbiotic ability, but, for most small metazoans, they mainly constitute food. Vertebrates are characterized by feeding by predation on larger preys, when compared to their ancestors who were filter feeders and ate micro organisms. Predation gives a strong selective advantage, not only due to the availability of new food resources but also by the ability to eliminate competitors for environmental resources (intraguild predation (IGP)). Unlike size structured IGP, intraspecific predation of juveniles, zygotes or gametes can be detrimental for species fitness in some circumstances. The ability of individuals to recognize highly polymorphic molecules on the surface of gametes present in the plankton and so distinguish self versus non-self gametes might have constituted a strong selective advantage in intraspecific competition. Here, I propose the theory that the capacity to rearrange receptors has been selected in ancestral vertebrates as a consequence of this strong need for discriminating between hetero-cannibalism versus filial cannibalism. This evolutionary origin sheds light on presently unexplained features of the immune system, including the existence of regulatory T cells and of non-pathogenic natural autoimmunity. PMID- 26286031 TI - Two nucleotide second messengers regulate the production of the Vibrio cholerae colonization factor GbpA. AB - BACKGROUND: The nucleotide second messengers cAMP and c-di-GMP allow many bacteria, including the human intestinal pathogen Vibrio cholerae, to respond to environmental stimuli with appropriate physiological adaptations. In response to limitation of specific carbohydrates, cAMP and its receptor CRP control the transcription of genes important for nutrient acquisition and utilization; c-di GMP controls the transition between motile and sessile lifestyles often, but not exclusively, through transcriptional mechanisms. In this study, we investigated the convergence of cAMP and c-di-GMP signaling pathways in regulating the expression of gbpA. GbpA is a colonization factor that participates in the attachment of V. cholerae to N-acetylglucosamine-containing surfaces in its native aquatic environment and the host intestinal tract. RESULTS: We show that c di-GMP inhibits gbpA activation in a fashion independent of the known transcription factors that directly sense c-di-GMP. Interestingly, inhibition of gbpA activation by c-di-GMP only occurs during growth on non-PTS dependent nutrient sources. Consistent with this result, we show that CRP binds to the gbpA promoter in a cAMP-dependent manner in vitro and drives transcription of gbpA in vivo. The interplay between cAMP and c-di-GMP does not broadly impact the CRP cAMP regulon, but occurs more specifically at the gbpA promoter. CONCLUSIONS: These findings suggest that c-di-GMP directly interferes with the interaction of CRP-cAMP and the gbpA promoter via an unidentified regulator. The use of two distinct second messenger signaling mechanisms to regulate gbpA transcription may allow V. cholerae to finely modulate GbpA production, and therefore colonization of aquatic and host surfaces, in response to discrete environmental stimuli. PMID- 26286032 TI - Study protocol: the effects of air pollution exposure and chronic respiratory disease on pneumonia risk in urban Malawian adults--the Acute Infection of the Respiratory Tract Study (The AIR Study). AB - BACKGROUND: Pneumonia is the 2nd leading cause of years of life lost worldwide and is a common cause of adult admissions to hospital in sub-Saharan Africa. Risk factors for adult pneumonia are well characterised in developed countries, but are less well described in sub-Saharan Africa where HIV is a major contributing factor. Exposure to indoor and outdoor air pollution is high, and tobacco smoking prevalence is increasing in sub-Saharan Africa, yet the contribution of these factors to the burden of chronic respiratory diseases in sub-Saharan Africa remains poorly understood. Furthermore, the extent to which the presence of chronic respiratory diseases and exposure to air pollution contribute to the burden of pneumonia is not known. DESIGN: The Acute Infection of the Respiratory Tract Study (The AIR Study) is a case-control study to identify preventable risk factors for adult pneumonia in the city of Blantyre, Malawi. Cases will be adults admitted with pneumonia, recruited from Queen Elizabeth Central Hospital, the largest teaching hospital in Malawi. Controls will be adults without pneumonia, recruited from the community. The AIR Study will recruit subjects and analyse data within strata defined by positive and negative HIV infection status. All participants will undergo thorough assessment for a range of potential preventable risk factors, with an emphasis on exposure to air pollution and the presence of chronic respiratory diseases. This will include collection of questionnaire data, clinical samples (blood, urine, sputum and breath samples), lung function data and air pollution monitoring in their home. Multivariate analysis will be used to identify the important risk factors contributing to the pneumonia burden in this setting. Identification of preventable risk factors will justify research into the effectiveness of targeted interventions to address this burden in the future. DISCUSSION: The AIR Study is the first study of radiologically confirmed pneumonia in which air pollution exposure measurements have been undertaken in this setting, and will contribute important new information about exposure to air pollution in urban SSA. Through identification of preventable risk factors, the AIR Study aims to facilitate future research and implementation of targeted interventions to reduce the high burden of pneumonia in SSA. PMID- 26286033 TI - Spatial inequity in access to healthcare facilities at a county level in a developing country: a case study of Deqing County, Zhejiang, China. AB - BACKGROUND: The inequities in healthcare services between regions, urban and rural, age groups and diverse income groups have been growing rapidly in China. Equal access to basic medical and healthcare services has been recognized as "a basic right of the people" by Chinese government. Spatial accessibility to healthcare facilities has received huge attention in Chinese case studies but been less studied particularly at a county level due to limited availability of high-resolution spatial data. This study is focused on measuring spatial accessibility to healthcare facilities in Deqing County. The spatial inequity between the urban (town) and rural is assessed and three scenarios are designed and built to examine which scenario is instrumental for better reducing the spatial inequity. METHODS: This study utilizes highway network data, Digital Elevation Model (DEM), location of hospitals and clinics, 2010 census data at the finest level - village committee, residential building footprint and building height. Areal weighting method is used to disaggregate population data from village committee level to residential building cell level. Least cost path analysis is applied to calculate the travel time from each building cell to its closest healthcare facility. Then an integral accessibility will be calculated through weighting the travel time to the closest facility between three levels. The spatial inequity in healthcare accessibility between the town and rural areas is examined based on the coverages of areas and populations. The same method is used to compare three scenarios aimed at reducing such spatial inequity - relocation of hospitals, updates of weighting values, and the combination of both. RESULTS: 50.03% of residents can reach a county hospital within 15 min by driving, 95.77% and 100% within 30 and 60 min respectively. 55.14% of residents can reach a town hospital within 5 min, 98.04% and 100% within 15 and 30 min respectively. 57.86% of residential building areas can reach a village clinic within 5 min, 92.65% and 99.22% within 10 and 15 min. After weighting the travel time between the three-level facilities, 30.87% of residents can reach a facility within 5 min, 80.46%% and 99.88% within 15 and 30 min respectively. CONCLUSIONS: The healthcare accessibility pattern of Deqing County has exhibited spatial inequity between the town and rural areas, with the best accessibility in the capital of the county and poorest in the West of the county. There is a high negative correlation between population ageing and healthcare accessibility. Allocation of more advanced medical and healthcare equipment and highly skillful doctors and nurses to village clinics will be an efficient means of reducing the spatial inequity and further consolidating the national medical security system. GIS (Geographical Information Systems) methods have proven successful method of providing quantitative evidence for policy analysis although the data sets and methods could be further improved. PMID- 26286034 TI - What is the theory? PMID- 26286035 TI - No matter who, no matter how... and no matter whether the white matter matters. Why theories of bilingual advantage in executive functioning are so difficult to falsify. PMID- 26286036 TI - Identifying the causal link: Two approaches toward understanding the relationship between bilingualism and cognitive control. PMID- 26286037 TI - Cold shock induction of recombinant Arctic environmental genes. AB - BACKGROUND: Heterologous expression of psychrophilic enzymes in E. coli is particularly challenging due to their intrinsic instability. The low stability is regarded as a consequence of adaptation that allow them to function at low temperatures. Recombinant production presents a significant barrier to their exploitation for commercial applications in industry. METHODS: As part of an enzyme discovery project we have investigated the utility of a cold-shock inducible promoter for low-temperature expression of five diverse genes derived from the metagenomes of marine Arctic sediments. After evaluation of their production, we further optimized for soluble production by building a vector suite from which the environmental genes could be expressed as fusions with solubility tags. RESULTS: We found that the low-temperature optimized system produced high expression levels for all putatively cold-active proteins, as well as reducing host toxicity for several candidates. As a proof of concept, activity assays with one of the candidates, a putative chitinase, showed that functional protein was obtained using the low-temperature optimized vector suite. CONCLUSIONS: We conclude that a cold-shock inducible system is advantageous for the heterologous expression of psychrophilic proteins, and may also be useful for expression of toxic mesophilic and thermophilic proteins where properties of the proteins are deleterious to the host cell growth. PMID- 26286040 TI - Impact of mode of delivery on the milk microbiota composition of healthy women. AB - Breast milk constitutes one of the most important sources of postnatal microbes. However, the influence of perinatal factors on the milk microbiome is still poorly understood. The aim of our study was to assess the impact of mode of delivery on the microbiome composition and diversity present in breast milk of healthy mothers. Mature milk samples (n=10) were taken from mothers after 1 month of exclusively breastfeeding. Microbiomes from milk samples were analyzed with 16S ribosomal RNA gene pyrosequencing and targeted quantitative polymerase chain reaction (PCR). Despite inter-individual variability in bacterial composition, The Principal Coordinates Analysis clearly separated milk microbiome from mothers with vaginal delivery (n=6) from those who undergo C-section (n=4). In addition, higher bacterial diversity and richness was found in milk samples from vaginal deliveries. Quantitative PCR data showed that higher levels of Bifidobacterium spp. were related significantly to lower levels of Staphylococcus spp. Despite the low sample size, our data suggest that mode of delivery has an important impact on milk microbiome composition. Further studies with larger sample sizes are needed to confirm these results and to understand the biological effects of C section associated microbes on infant's health. PMID- 26286039 TI - Effect of an intervention to enhance guideline adherence of occupational physicians on return-to-work self-efficacy in workers sick-listed with common mental disorders. AB - BACKGROUND: Since a higher level of self-efficacy in common mental disorders is associated with earlier return-to-work (RTW), it is important to know if work related self-efficacy can be increased by occupational health care. The primary aim of this study was to evaluate whether an intervention to enhance guideline adherence of occupational physicians lead to an increase in RTW self-efficacy in workers three months later. The secondary aim was to evaluate whether the intervention modified the association between RTW self-efficacy and return-to work three months later. METHODS: A total of 66 occupational physicians participated in the study. They were randomized into two groups; the intervention group received a training, the control group did not. The training aimed to enhance adherence to a mental health guideline that contained strategies that are supposed to enhance RTW self-efficacy. In 128 sick-listed workers guided by these occupational physicians, RTW self-efficacy, RTW, and personal, health-related and work-related variables were measured at baseline and three months later. Generalized linear mixed models analysis and linear mixed models analysis were used for the evaluations. RESULTS: In workers whose occupational physicians had received the training RTW self-efficacy increased significantly more than in workers whose occupational physicians had participated in the control group (t = 2.626, p <= .05). Higher baseline RTW self-efficacy scores were significantly more often associated with full RTW than with no RTW three months later (OR 2.20, 95 % CI 1.18-4.07), but the intervention did not affect this association. CONCLUSIONS: This study showed that a training to enhance guideline adherence of occupational physicians leads to increased RTW self-efficacy in workers sick listed with common mental disorders during the first months of sickness absence in a real-life occupational health care setting. This insight is helpful for optimizing the recovery and RTW process, and for understanding the role of RTW self-efficacy in this process. TRIAL REGISTRATION: ISRCTN86605310. PMID- 26286038 TI - Characteristics of patients with primary open angle glaucoma and normal tension glaucoma at a university hospital: a cross-sectional retrospective study. AB - BACKGROUND: The characteristics of glaucoma patients and their response to therapy may differ by institution, region and country. Therefore, clinicians should understand the distinctiveness of their patients. Here, we profile primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) patients at a major university hospital in Japan. METHODS: This study included 523 eyes from 523 POAG and NTG patients who underwent full clinical ophthalmologic evaluations at Tohoku University Hospital. Clinical characteristics such as age, sex, visual acuity, intraocular pressure, Humphrey field analyzer-measured mean deviation (MD) and MD slope were collected retrospectively. MD slope was calculated from MD data that included the first baseline measurement of MD and 4 subsequent, consecutive, reliable measurements of MD. Refractive error was analyzed in a subgroup with no history of refractive surgery, including intraocular lens implantation. Patient characteristics were analyzed separately in the groups of patients with low (<15 mmHg) and high IOP (>=15 mmHg) and in the groups with MD slope >=-1.0 and <-1.0 dB/year. RESULTS: Mean age, visual acuity (median), IOP, pre-treatment IOP (from patient history), refractive error and MD were 61.7 +/- 12.5 years, -0.08 (interquartile range -0.08 to 0.05) LogMAR, 13.87 +/- 3.37 mmHg, 18.35 +/- 6.26 mmHg, -4.48 +/- 3.81 diopters and -11.73 +/- 8.83 dB, respectively. POAG and NTG patients had significant differences in mean age (63.4 +/- 12.4 vs. 60.7 +/- 12.5 years, P < 0.01), visual acuity, IOP (14.95 +/- 4.20 vs. 13.21 +/- 2.54 mmHg, P < 0.01) and MD (-13.85 +/- 9.32 vs. -10.45 +/- 8.27 dB, P < 0.01). Interestingly, MD slope was slightly steeper in the low-IOP group than in the high-IOP group, although the difference was not statistically significant (-0.85 vs. -0.70 dB/year, P = 0.31). Baseline MD was significantly worse in the group with MD slope <-1.0 dB/year than in the group with MD slope >=-1.0 dB/year (-11.56 vs. 7.64 dB/year, P < 0.01). CONCLUSIONS: We identified characteristics of glaucoma patients at a university hospital that may reflect the specialized nature of such an institution. PMID- 26286042 TI - Lutein intake at the age of 1 year and cardiometabolic health at the age of 6 years: the Generation R Study. AB - Lutein is a carotenoid with strong antioxidant properties. Previous studies in adults suggest a beneficial role of lutein on cardiometabolic health. However, it is unknown whether this relation also exists in children; therefore, we aimed to assess the relation between lutein intake at 13 months of age and cardiometabolic outcomes at the age of 6 years. We included 2044 Dutch children participating in a population-based prospective cohort study. Diet was measured at 13 months of age with an FFQ. Lutein intake was standardised for energy and beta-carotene intake. Blood pressure, anthropometrics, serum lipids and insulin were measured at the age of 6 years. Dual-energy X-ray absorptiometry was performed to measure total and regional fat and lean mass. A continuous cardiometabolic risk factor score was created, including the components body fat percentage, blood pressure, insulin, HDL-cholesterol and TAG. Age- and sex-specific standard deviation scores were created for all outcomes. Multivariable linear regression was performed, including socio-demographic and lifestyle variables. Median (energy-standardised) lutein intake was 1317 mcg/d (95% range 87, 6069 mcg/d). There were no consistent associations between lutein intake at 13 months and anthropometrics and body composition measures at 6 years of age. In addition, lutein intake was not associated with a continuous cardiometabolic risk factor score, nor was it associated with any of the individual components of the cardiometabolic risk factor score. Results from this large population-based prospective cohort study do not support the hypothesis that lutein intake early in life has a beneficial role for later cardiometabolic health. PMID- 26286041 TI - Effects of Kaixinjieyu, a Chinese herbal medicine preparation, on neurovascular unit dysfunction in rats with vascular depression. AB - BACKGROUND: Kaixinjieyu (KJ), derived from Kaixin and Sini powder, is an effective Chinese herbal medicine preparation used in the treatment of vascular depression (VD). We hypothesize that broad antidepressant effect of KJ results from the improved neurovascular unit (NVU) function via neurogenesis, permeability of blood-brain barrier (BBB) and balance of the fibrinolytic system. METHODS: A VD model of rat was established by chronic unpredictable mild stress and separation after ligation of the bilateral common carotid arteries. The rats were treated with KJ and fluoxetine hydrochloride (FLU) for 21 days, respectively. The behavior and cerebral perfusion were investigated and then NVU functions including neurogenesis, permeability of BBB and balance of the fibrinolytic system were studied using a number of biomarkers and TUNEL assay. RESULTS: KJ significantly increased sucrose preference, moving distance, number of rearing and cortical blood flow. NVU functions measured by brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) and tissue plasminogen activator (t-PA) proteins and mRNA, zona occludens protein-1 (ZO-1), occludin and claudin-5 proteins increased significantly, whereas, plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-2 (MMP-2) proteins, mRNA and apoptotic rates of neurons decreased significantly with treatment of KJ. FLU has a function similar to KJ in behavior, regulation of BDNF, TrkB, MMP-2, occludin and apoptotic rates of cells. CONCLUSIONS: KJ has function of reducing depression-like behavior and improving cerebral hypoperfusion, which might be mediated by the up-regulation of neurogenesis and tight junction of BBB, and balance of the fibrinolytic system. The results imply that KJ is better than FLU in improving cerebral hypoperfusion and the fibrinolytic system. PMID- 26286043 TI - Hyper-activated PI3K-delta in immunodeficiency. PMID- 26286044 TI - Molecular and morphological data supporting phylogenetic reconstruction of the genus Goniothalamus (Annonaceae), including a reassessment of previous infrageneric classifications. AB - Data is presented in support of a phylogenetic reconstruction of the species-rich early-divergent angiosperm genus Goniothalamus (Annonaceae) (Tang et al., Mol. Phylogenetic Evol., 2015) [1], inferred using chloroplast DNA (cpDNA) sequences. The data includes a list of primers for amplification and sequencing for nine cpDNA regions: atpB-rbcL, matK, ndhF, psbA-trnH, psbM-trnD, rbcL, trnL-F, trnS-G, and ycf1, the voucher information and molecular data (GenBank accession numbers) of 67 ingroup Goniothalamus accessions and 14 outgroup accessions selected from across the tribe Annoneae, and aligned data matrices for each gene region. We also present our Bayesian phylogenetic reconstructions for Goniothalamus, with information on previous infrageneric classifications superimposed to enable an evaluation of monophyly, together with a taxon-character data matrix (with 15 morphological characters scored for 66 Goniothalamus species and seven other species from the tribe Annoneae that are shown to be phylogenetically correlated). PMID- 26286045 TI - Vanishing Boundaries between Chemistry and Biology: Reflections on Our Journal. PMID- 26286046 TI - Ionization of Water Clusters Mediated by Exciton Energy Transfer from Argon Clusters. AB - The exciton energy deposited in an argon cluster (Arn, ?n = 20?) using VUV radiation is transferred to softly ionize doped water clusters ((H2O)n, n = 1-9), leading to the formation of nonfragmented clusters. Following the initial excitation, electronic energy is channeled to ionize the doped water cluster while evaporating the Ar shell, allowing identification of fragmented and complete water cluster ions. Examination of the photoionization efficiency curve shows that cluster evaporation from excitons located above 12.6 eV is not enough to cool the energized water cluster ion and leads to their dissociation to (H2O)n 2H(+) (protonated) clusters. PMID- 26286047 TI - Rational Design of Competitive Electrocatalysts for Hydrogen Fuel Cells. AB - The large-scale application of one of the most promising clean and renewable sources of energy, hydrogen fuel cells, still awaits efficient and cost-effective electrocatalysts for the oxygen reduction reaction (ORR) occurring on the cathode. We demonstrate that truly rational design renders electrocatalysts possessing both qualities. By unifying the knowledge on surface morphology, composition, electronic structure, and reactivity, we solve that trimetallic sandwich-like structures are an excellent choice for optimization. Their constituting species are expected to couple synergistically yielding reaction environment stability, cost-effectiveness, and tunable reactivity. This cooperative-action concept enabled us to predict two advantageous ORR electrocatalysts: Pd/Fe/W(110) and Au/Ru/W(110). Density functional theory calculations of the reaction free-energy diagrams suggest that these materials are more active toward ORR than the so-far best Pt-based catalysts. Our designing concept advances also a general approach for engineering advanced materials. PMID- 26286048 TI - Impact of Vibronic Couplings on Perceived Colors: Two Anthraquinones as a Working Example. AB - The accurate simulation of the dye colors remains a significant challenge for theoreticians, notably due to the sensitivity of the human eyes that are able to distinguish variations of hues corresponding to trifling energetic shifts. Using time-dependent density functional theory and two hybrid functionals, we have simulated vibrationally resolved absorption spectra of two anthraquinone derivatives (solvent blue 35 and solvent green 3) solvated in cyclohexane. Comparisons with recent experiments demonstrate the efficiency of the omegaB97X D/6-31++G(d,p) approach for these structures. The impact of microscopic vibronic couplings on the macroscopic chromatic coordinates of the dyes is quantified. This work unravels the key role of these couplings and is consequently a step further in the modeling of human-perceived colors from purely ab initio models. PMID- 26286049 TI - Protonated Carboxyl Anchor for Stable Adsorption of Ru N749 Dye (Black Dye) on a TiO2 Anatase (101) Surface. AB - We have investigated the adsorption stability of ruthenium N749 dye [black dye (BD)], a highly efficient dye for dye-sensitized solar cells (DSCs), through protonated and deprotonated carboxyl group anchors on a TiO2 anatase (101) surface by using first-principles calculations. Geometry optimizations of the surface system with a supercell and the UV-visible spectrum calculation of the optimized dye structure were carried out. Among the configurations with one and two anchors, the BD adsorption anchored with one protonated carboxyl group was found to be the most stable, in contrast to most previous reports. Hydrogen bonding between the proton retained in BD and the surface oxygen is responsible for the stability of the protonated anchor. We confirmed that the calculated UV visible spectrum of the most stable dye structure shows the best consistency with the experimental data. It is also demonstrated that the electronic density of states largely depends on the proton position. This novel aspect of adsorption via a protonated carboxyl anchor gives a new perspective for interfacial electronic processes of DSCs. PMID- 26286050 TI - A Photoconductive, Thiophene-Fullerene Double-Cable Polymer, Nanorod Device. AB - Gold/double-cable copolymer/gold multisegmented nanorods were prepared electrochemically via a template-based method. These "bulk heterojunction" nanorods showed photoconductivity providing us with a platform to study photoinduced charge separation/transport at the nanointerface and begin to think about the rational design of nanoscale solar cells based on such structures. PMID- 26286051 TI - High-Resolution Rotational Spectroscopy of a Cyclic Ether. AB - The conformational landscape of crown ethers has constituted a central topic in the development of host-guest supramolecular chemistry. We report a high resolution rotational study of a crown ether, 1,4,7,10,13 pentaoxacyclopentadecane (15-crown-5), by means of molecular beam Fourier transform microwave spectroscopy. The considerable size and the broad range of conformations allowed by the flexibility of the cyclic backbone of this ether pose important challenges to spectroscopy approaches. In this investigation, three stable rotamers of the 15-crown-5 ether have been identified and characterized through their rotational constants and centrifugal distortion coefficients. Ab initio quantum calculations at the MP2 level predict these conformers as the most stable ones for the title system and reproduce accurately their distinct structural features. The results pave the ground for an extensive survey of the conformational landscape of the 15-crown-5 and related cyclic ethers in the near term. PMID- 26286052 TI - Adsorption and Photochemical Properties of a Molecular CO2 Reduction Catalyst in Hierarchical Mesoporous ZSM-5: An In Situ FTIR Study. AB - As part of our recent effort to attach well-defined molecular photocatalysts to solid-state surfaces, this present study investigates adsorption and photochemical properties of a tricarbonyl rhenium(I) compound, Re(bpy)(CO)3Cl (bpy = 2,2'-bipyridine), in hierarchical mesoporous ZSM-5. The molecular Re(I) catalyst, a Ru(bpy)3(2+) photosensitizer, and an amine-based electron donor were coadsorbed in the mesopores of the hierarchical ZSM-5 through simple liquid-phase adsorption. The functionalized ZSM-5 was then characterized with infrared and UV visible spectroscopies and was tested in CO2 reduction photocatalysis at the gas surface interface. In the mesoporous ZSM-5, CO2 molecules were adsorbed on the amine electron-donor molecules as bicarbonate, which would release CO2 upon light irradiation to react with the Re(I) catalyst. The formation of important reaction intermediates, particularly a Re-carboxylato species, was revealed with in situ Fourier transform infrared spectroscopy in combination with isotopic labeling. The experimental results indicate that hierarchical mesoporous zeolites are promising host materials for molecular photocatalysts and that zeolite mesopores are potential "reaction vessels" for CO2 reduction photocatalysis at the gas solid interface. PMID- 26286053 TI - Chemical Reaction Rates from Ring Polymer Molecular Dynamics: Zero Point Energy Conservation in Mu + H2 -> MuH + H. AB - A fundamental issue in the field of reaction dynamics is the inclusion of the quantum mechanical (QM) effects such as zero point energy (ZPE) and tunneling in molecular dynamics simulations, and in particular in the calculation of chemical reaction rates. In this work we study the chemical reaction between a muonium atom and a hydrogen molecule. The recently developed ring polymer molecular dynamics (RPMD) technique is used, and the results are compared with those of other methods. For this reaction, the thermal rate coefficients calculated with RPMD are found to be in excellent agreement with the results of an accurate QM calculation. The very minor discrepancies are within the convergence error even at very low temperatures. This exceptionally good agreement can be attributed to the dominant role of ZPE in the reaction, which is accounted for extremely well by RPMD. Tunneling only plays a minor role in the reaction. PMID- 26286054 TI - Nonmechanical Conductance Switching in a Molecular Tunnel Junction. AB - We present a molecular junction composed of a donor (polyacetylene strands) and an acceptor (malononitrile) connected together via a benzene ring and coupled weakly to source and drain electrodes on each side, for which a gate electrode induces intramolecular charge transfer, switching reversibly the character of conductance. Using a new brand of density functional theory, for which orbital energies are similar to the quasiparticle energies, we show that the junction displays a single, gate-tunable differential conductance channel in a wide energy range. The gate field must align parallel to the displacement vector between donors and acceptor to affect their potential difference; for strong enough fields, spontaneous intramolecular electron transfer occurs. This event radically affects conductance, reversing the charge of carriers, enabling a spin-polarized current channel. We discuss the physical principles controlling the operation of the junction and find interplay of quantum interference, charging, Coulomb blockade, and electron-hole binding energy effects. We expect that this switching behavior is a generic property for similar donor-acceptor systems of sufficient stability. PMID- 26286055 TI - Probing Photosynthetic Energy and Charge Transfer with Two-Dimensional Electronic Spectroscopy. AB - Two-dimensional electronic spectroscopy (2DES) has emerged as a powerful method for elucidating the structure-function relationship in photosynthetic systems. In this Perspective, we discuss features of two-dimensional spectroscopy that make it highly suited to address questions about the underlying electronic structure that guides energy- and charge-transfer processes in light-harvesting materials. We briefly describe a pulse-shaping-based implementation of two-dimensional spectroscopy that is making the method widely accessible to problems spanning frequency regimes from the ultraviolet to the mid-infrared. We illustrate the utility of 2DES in the context of our recent studies of the primary energy transfer and charge separation events in the photosystem II reaction center, discussing remaining challenges and speculating about exciting future directions for the field of multidimensional spectroscopy. PMID- 26286056 TI - Intensive Edge Effects of Nanographenes in Molecular Adsorptions. AB - Graphene has become a primary material in nanotechnology and has a wide range of potential applications in electronics. Fabricated graphenes are generally nanosized and composed of stacked graphene layers. The edges of nanographenes predominantly influence the chemical and physical properties because nanographene layers have a large number of edges. We demonstrated the edge effects of nanographenes and discrimination against basal planes in molecular adsorption using grand canonical Monte Carlo simulations. The edge sites of nanographene layers have relatively strong Coulombic interactions as a result of the partial charges at the edges, but the basal planes rarely have Coulombic interactions. CO2 and N2 prefer to be adsorbed on the edge sites and basal planes, respectively. As a result of these different preferences, the separation ability of CO2 is higher than that of N2 in the low-pressure region, thereby offering selective adsorptions, reactions, and separations on nanographene edges. PMID- 26286057 TI - Dynamic Microscopy Study of Ultrafast Charge Transfer in a Hybrid P3HT/Hyperbranched CdSe Nanoparticle Blend for Photovoltaics. AB - We present a spectroscopic investigation on a new hyperbranched cadmium selenide nanocrystals (CdSe NC)/poly(3-hexylthiophene) (P3HT) blend, a potentially good active component in hybrid photovoltaics. Combined ultrafast transient absorption spectroscopy and morphological investigations by means of an ultrafast confocal microscope reveal a strong influence of the complex local structure on the photogenerated carrier dynamics. In particular, we map the electron-transfer process across the hybrid NC/polymer interface, and we reveal that charge separation occurs through a preferential pathway from the CdSe nanobranches to the P3HT chains. Efficient charge generation at the distributed heterojunction is also confirmed by scanning kelvin probe force microscopy measurements. PMID- 26286058 TI - NaDyF4 Nanoparticles as T2 Contrast Agents for Ultrahigh Field Magnetic Resonance Imaging. AB - A major limitation of the commonly used clinical MRI contrast agents (CAs) suitable at lower magnetic field strengths (<3.0 T) is their inefficiency at higher fields (>7 T), where next-generation MRI scanners are going. We present dysprosium nanoparticles (beta-NaDyF4 NPs) as T2 CAs suitable at ultrahigh fields (9.4 T). These NPs effectively enhance T2 contrast at 9.4 T, which is 10-fold higher than the clinically used T2 CA (Resovist). Evaluation of the relaxivities at 3 and 9.4 T show that the T2 contrast enhances with an increase in NP size and field strength. Specifically, the transverse relaxivity (r2) values at 9.4 T were ~64 times higher per NP (20.3 nm) and ~6 times higher per Dy(3+) ion compared to that at 3 T, which is attributed to the Curie spin relaxation mechanism. These results and confirming phantom MR images demonstrate their effectiveness as T2 CAs in ultrahigh field MRIs. PMID- 26286059 TI - Graphene Oxide Nanosheet Induced Intrachain Conformational Ordering in a Semicrystalline Polymer. AB - The physical origin of graphene oxide nanosheet (GONS)-driven polymer crystallization was studied from the perspective of intrachain conformational ordering. Time-resolved Fourier-transform infrared spectroscopy indicated that both conformational ordering and crystallization of isotactic polypropylene (iPP) were obviously accelerated by the presence of GONSs, indicating their efficient nucleation activity for iPP crystallization. Furthermore, the ordering of long helical segments occurred prior to the crystallization of iPP, as revealed by two dimensional correlation infrared analysis. Compared to pure bulk system, the presence of GONSs was in favor of the formation of long ordering segments, especially at the early stage, accompanied by considerable enhancement of the crystallization kinetics. GONS-driven iPP crystallization was suggested to be attributed to this GONS-induced intrachain conformational ordering. PMID- 26286060 TI - The Role of Confined Water in Ionic Liquid Electrolytes for Dye-Sensitized Solar Cells. AB - Ionic liquids (ILs) provide an attractive medium for various chemical and redox reactions, where they are generally regarded as hydrophobic. However, Seddon et al. discovered that 4-10 wt % water absorbs into ILs that contain bulky anions, and Cammarata et al. found that the molecular state of water in ILs is dramatically different from that of bulk liquid water or that of water vapor. To determine the microstructure of water incorporated into ILs and the impact on properties, we carried out first-principles-based molecular dynamics simulations. We find water in three distinct phases depending on water content, and that the transport properties depend on the nature of the water phases. These results suggest that the optimal water content is ~10% mole fraction of water molecules (~1.1 wt %) for applications such as nonvolatile electrolytes for dye-sensitized solar cells (DSSCs). This suggests a strategy for improving the performance of IL DSSC by replacing water with additives that would play the same role as water (since too much water can deteriorate performance at the anode-dye interface). PMID- 26286061 TI - The 2014 Impact Factor: ACS Chemical Neuroscience continues to rise. PMID- 26286063 TI - The role of pi-bonding on the high temperature structure of the double perovskites Ba2CaUO6 and BaSrCaUO6. AB - The high temperature structural behaviour of the uranium perovskites Ba2CaUO6 and BaSrCaUO6 has been investigated using a combination of synchrotron X-ray and neutron powder diffraction. Ba2CaUO6 undergoes a complex sequence of structures associated with the progressive loss of cooperative octahedral tilting: P21/n -> I2/m -> I2/m -> I4/m -> Fm3[combining macron]m. The observation of the intermediate tetragonal structure, I4/m, in this, contrasts with the previously reported rhombohedral R3[combining macron] intermediate formed by the Ba2SrUO6 oxide. The importance of pi-bonding in determining the structural sequence is discussed. PMID- 26286064 TI - Moulding calixarenes for biomacromolecule targeting. AB - After their successful use as a preorganized platform for the preparation of receptors for metal ions and small neutral molecules over the last 15 years, calixarenes are enjoying a renaissance of popularity as scaffolds for ligands that are able to efficiently and selectively target macromolecules such as proteins/enzymes, nucleic acids and lipids. This feature article summarizes the peculiar factors characterizing the calixarene structure and properties, as well as outlines the main rules that can be used to turn such macrocycles into efficient and successful ligands for these classes of biomacromolecules. Factors that affect the multivalent properties of calixarenes, such as the size, conformation and stereochemical presentation of binding groups or their amphiphilicity and hybrid character, are described in detail with the use of a few selected examples from the literature. Perspectives and applications of these ligands in bionanotechnology and nanomedicine, such as protein sensing and inhibition, gene-delivery, targeted drug-delivery and cell imaging, are also discussed. PMID- 26286065 TI - In vitro and in vivo studies of the metabolic activation of 8-epidiosbulbin E acetate. AB - Furanoid 8-epidiosbulbin E acetate (EEA) is a major constituent of herbal medicine Dioscorea bulbifera L. (DB), a traditional Chinese medicine herb. Our preliminary studies demonstrated that administration of EEA caused acute hepatotoxicity in mice, and the observed toxicity required cytochromes P450 mediated metabolism. Metabolic activation studies of EEA were performed in vitro and in vivo. Microsomal incubations of EEA supplemented with N-acetyl lysine (NAL) and glutathione (GSH) generated six metabolites (M1-M6). M1-M4 were characterized as pyrrole derivatives, and M5 and M6 were pyrrolinones. M2-M6 were detected in bile and/or urine of rats given EEA. Dimethyldioxirane-mediated oxidation of EEA in the presence of NAL and GSH produced M1-M6, all of which were generated in microsomal incubations. The structures of M3 and M6 were confirmed by (1)H and (13)C NMR. These findings provide evidence for the metabolic activation of EEA to the corresponding cis-enedial intermediate both in vitro and in vivo. Ketoconazole inhibited the microsomal production of the cis-enedial, and P450 3A4 was found to be the primary enzyme involved in the bioactivation of EEA. PMID- 26286066 TI - Effect of induction therapy on the expression of molecular markers associated with rejection and tolerance. AB - BACKGROUND: Induction therapy can improve kidney transplantation (KTx) outcomes, but little is known about the mechanisms underlying its effects. METHODS: The mRNA levels of T cell-related genes associated with tolerance or rejection (CD247, GZMB, PRF1, FOXP3, MAN1A1, TCAIM, and TLR5) and lymphocyte subpopulations were monitored prospectively in the peripheral blood of 60 kidney transplant recipients before and 7, 14, 21, 28, 60, 90 days, 6 months, and 12 months after KTx. Patients were treated with calcineurin inhibitor-based triple immunosuppression and induction with rabbit anti-thymocyte globulin (rATG, n = 24), basiliximab (n = 17), or without induction (no-induction, n = 19). A generalized linear mixed model with gamma distribution for repeated measures, adjusted for rejection, recipient/donor age and delayed graft function, was used for statistical analysis. RESULTS: rATG treatment caused an intense reduction in all T cell type population and natural killer (NK) cells within 7 days, then a slow increase and repopulation was observed. This was also noticed in the expression levels of CD247, FOXP3, GZMB, and PRF1. The basiliximab group exhibited higher CD247, GZMB, FOXP3 and TCAIM mRNA levels and regulatory T cell (Treg) counts than the no-induction group. The levels of MAN1A1 and TLR5 mRNA expressions were increased, whereas TCAIM decreased in the rATG group as compared with those in the no-induction group. CONCLUSION: The rATG induction therapy was associated with decreased T and NK cell-related transcript levels and with upregulation of two rejection-associated transcripts (MAN1A1 and TLR5) shortly after KTx. Basiliximab treatment was associated with increased absolute number of Treg cells, and increased level of FOXP3 and TCAIM expression. PMID- 26286067 TI - DNA Interaction, Photocleavage and Topoisomerase I Inhibition by Ru(II) Complex with a New Ligand Possessing Phenazine Unit. AB - A new ruthenium complex with a dppz-like ligand pyidppz, [Ru(bpy)2(pyidppz)](2+) (pyidppz = 2-(pyridine-2-yl)imidazo-[4,5-b]dipyrido-[3,2-a:2',3'-c]phenazine) has been synthesized and characterized by ES-MS, elemental analysis, (1)H NMR. Intercalative mode of the complex bound to calf thymus DNA has been supported by different spectroscopic methods and viscosity measurements. The introduction of phenazine unit may be one of the main reasons for the weak emission of Ru(II) complex in aqueous solution. Under irradiation, this complex can efficiently cleave DNA. And the photocleavage reaction of the complex is found to be inhibited in the presence of singlet oxygen scavenger. Topoisomerase inhibition and DNA strand passage assay demonstrated that [Ru(bpy)2(pyidppz)](2+) and its parent complex [Ru(bpy)2(pyip)](2+) (pyip = 2-(pyridine-2-yl)imidazo[4,5 f][1,10]phenanthroline) can act as efficient catalytic inhibitor of DNA topoisomerase I. PMID- 26286068 TI - Familial hematological malignancies: ASXL1 gene investigation. AB - PURPOSE: Familial aggregation among patients with several hematological malignancies has been revealed. This emphasizes the importance of genetic factors. Only few genes predisposing to familial hematological malignancies have been reported until now due to the low occurrence. We have described in previous study PRF1 and CEBPA variants that might contribute to the background of genetic factors, which encourage us to extend our investigations to other cooperating genes. The aim of this study is to determine whether germline additional sex combs-like 1 (ASXL1) gene mutations may be involved? METHODS/PATIENTS: In this study, we investigated the candidate gene ASXL1 by direct sequencing in 88 unrelated Tunisian and French families with aggregated hematological malignancies. RESULTS: We report a new p.Arg402Gln germline missense substitution in two related Tunisian patients which has not been previously described. We identified here this variant for the first time in non-Hodgkin lymphoma. The p.Arg402Gln variant was not found in 200 control chromosomes. In silico analysis has predicted potential deleterious effect on ASXL1 protein. CONCLUSIONS: From an extended candidate genes analyzed in the field of familial hematological malignancies, ASXL1 might be involved. This variant should be considered since a potential damaging effect was predicted by in silico analysis, with a view to develop functional assay in order to investigate the biological assessment. PMID- 26286069 TI - Short stature in retinoblastoma survivors: a cross-sectional study of 138 patients. AB - PURPOSE: Short stature has been reported in pediatric cancer survivors. Data on retinoblastoma survivors are limited. We conducted a cross-sectional study to assess the height in retinoblastoma survivors. METHOD: The recorded height was compared with median height for age and sex as per the Indian Academy of Pediatrics. Z-score less than -2 was considered short statured. RESULT: Thirty percent of the survivors were short statured. The mean height was shorter than the mean 50th percentile height (119.7 +/- 14.8 vs 128.7 +/- 15 cm, p < 0.001). Previous chemotherapy showed a trend toward association (p = 0.09). CONCLUSION: Short stature affects a significant number of retinoblastoma survivors. PMID- 26286070 TI - End-of-life care communications and shared decision-making in Norwegian nursing homes--experiences and perspectives of patients and relatives. AB - BACKGROUND: Involving nursing home patients and their relatives in end-of-life care conversations and treatment decisions has recently gained increased importance in several Western countries. However, there is little knowledge about how the patients themselves and their next-of-kin look upon involvement in end-of life care decisions. The purpose of this paper is to explore nursing home patients' and next-of-kin's experiences with- and perspectives on end-of-life care conversations, information and shared decision-making. METHODS: The study has a qualitative and explorative design, based on a combination of individual interviews with 35 patients living in six nursing homes and seven focus group interviews with 33 relatives. The data was analysed applying a "bricolage" approach". Participation was based on informed consent, and the study was approved by the Regional Committees for Medical and Health Research Ethics. RESULTS: Few patients and relatives had participated in conversations about end of-life care. Most relatives wanted such conversations, while the patients' opinions varied. With some exceptions, patients and relatives wanted to be informed about the patient's health condition. The majority wanted to be involved in the decision-making process, but leave the final decisions to the health professionals. Among the patients, the opinion varied; some patients wanted to leave the decisions more or less completely to the nursing home staff. Conversations about end-of-life care issues are emotionally challenging, and very few patients had discussed these questions with their family. The relatives' opinions of the patient's preferences were mainly based on assumptions; they had seldom talked about this explicitly. Both patients and relatives wanted the staff to raise these questions. CONCLUSION: Nursing home staff should initiate conversations about preferences for end-of-life care, assisting patients and relatives in talking about these issues, while at the same time being sensitive to the diversity in opinions and the timing for such conversations. As the popularity of advance care planning increases in many Western countries, discussions of patients' and relatives' perspectives will be of great interest to a broader audience. PMID- 26286071 TI - A Narrative Review of Evidence-Based Preventive Options for Chronic Migraine. AB - Chronic migraine is a debilitating disorder that affects 2 % of the global population and imparts a significant societal and economic impact. The cornerstones of chronic migraine management include making an accurate diagnosis, patient education, treatment of comorbid conditions, and selection of an appropriate, evidence-based acute and preventive treatment regimen. Although it is common to treat chronic migraine with preventive medications effective for episodic migraine, a number of treatment options exist with specific evidence for effectiveness in chronic migraine. Currently, onabotulinumtoxinA injections are the only FDA-approved preventive treatment for chronic migraine. A number of non medication treatment options including occipital nerve and supraorbital nerve stimulation have shown promise as effective prevention for patients either unable to tolerate or unable to obtain relief from oral medications, but more research is necessary. PMID- 26286072 TI - Outcomes of Isolated Tibial Endovascular Interventions for Tissue Loss in CLI Patients on Hemodialysis. AB - PURPOSE: To compare the objective performance goals (OPGs) and patient-centered outcomes of isolated tibial interventions in patients with tissue loss who were on hemodialysis (HD) to patients with tissue loss who were not on HD. METHODS: Interrogation of a prospectively maintained database identified 242 critical limb ischemia (CLI) patients who underwent isolated tibial interventions for tissue loss in a single limb between 2007 and 2012. The 78 patients (mean age 66+/-12 years; 44 men) on HD were compared with 164 patients (mean age 50+/-13 years; 82 men) who were not on HD. There was an equal distribution of the tibial vessels treated; 152 (63%) patients had more than one treated tibial vessel. Patient centered outcomes of clinical efficacy (absence of recurrent symptoms, maintenance of ambulation, and no major amputation), amputation-free survival (AFS), and freedom from major adverse limb events (MALE) were evaluated. The Society for Vascular Surgery OPGs were defined at 30 days and 1 year. RESULTS: The 30-day major adverse cardiac events was significantly higher (p=0.004) in the HD group (5, 5%) compared with the no-HD group (0%), but both remained under the stated OPG of <=10%. The 30-day MALE rates were significantly higher than the stated <=9% OPG at 13% and 18% for the no-HD and HD groups, respectively. At 1 year, the rates for AFS, freedom from MALE, limb salvage, and survival did not achieve the stated Society for Vascular Surgery OPGs in the HD group. Clinical efficacy was 61% and 25% at 3 years for the no-HD and HD groups, respectively (p<0.01). Overall, AFS was 54% and 22% and freedom from MALE was 56% and 27% at 3 years for the no-HD and HD groups, respectively (both p<0.01). CONCLUSION: Tibial intervention for tissue loss in patients on HD is a valid treatment option but is associated with a high MALE rate. Three-year outcomes remain relatively poor, with <25% success in terms of clinical efficacy and AFS. PMID- 26286074 TI - Application of the "ORC" to Critical Limb Ischemia. PMID- 26286073 TI - Late Rupture of Abdominal Aortic Aneurysm After Previous Endovascular Repair: A Systematic Review and Meta-analysis. AB - PURPOSE: To report a systematic literature review of late rupture of abdominal aortic aneurysm (AAA) after endovascular aneurysm repair (EVAR) and the results of a pooled analysis of causes, treatment, and outcomes. METHODS: Electronic information sources and bibliographic reference lists were interrogated using a combination of free text and controlled vocabulary searches; 11 articles were ultimately identified that fulfilled the inclusion criteria. The articles reported a total of 190 patients who were included in the qualitative and quantitative synthesis. Mortality within 30 days or during the admission with aneurysm rupture was a primary endpoint; major perioperative morbidity was a secondary endpoint. A meta-analysis was performed for 30-day/in-hospital mortality using the random effects model. RESULTS: A total of 152 ruptures occurred after 16,974 EVAR procedures reported by 8 of the case series, giving an incidence of 0.9% [95% confidence interval (CI) 0.77 to 1.05]. The mean time to rupture was 37 months. Twenty-nine percent (95% CI 20 to 39) of the patients had at least one previous secondary endovascular intervention following the initial EVAR, and 37% (95% CI 30 to 45) were not compliant with surveillance. Type I and III endoleaks were the predominant causes of rupture. Open surgical treatment was undertaken in 61% (95% CI 53 to 68) of the patients who underwent treatment. The pooled estimate for perioperative mortality was 32% (95% CI 24 to 41). A significantly lower mortality was found with endovascular treatment than open surgical management (p=0.027). CONCLUSION: Graft-related endoleaks appear to be the predominant causes of late aneurysm rupture. Quality of and compliance with post-EVAR surveillance are important factors in late rupture; a large proportion of late ruptures are amenable to endovascular treatment. PMID- 26286075 TI - Is It the Arc of Riolan or Meandering Mesenteric Artery? PMID- 26286076 TI - [Proximal femoral fractures in the elderly]. AB - Proximal femoral fractures represent an increasing major healthcare problem due to the demographic changes in this aging population and are associated with the highest mortality among fractures in elderly patients after suffering insufficiency injuries (so-called fragility fractures). The main aim in the treatment of orthogeriatric patients who suffered from a proximal femoral fracture is the preservation of function and independency. Given the high prevalence of comorbidities in these patients, interdisciplinary and interprofessional approaches are required. The use of modern osteosynthesis procedures can provide an improved, individualized surgical treatment with early full weight bearing of the affected extremity. Another aspect is the accompanying geriatric treatment which is associated with a significant reduction of perioperative and postoperative complications. In addition to acute treatment, the organization of secondary fracture prevention is a crucial pillar of treatment. This article provides an overview of the essential elements of orthogeriatric trauma surgery in elderly patients following proximal femoral fractures. PMID- 26286078 TI - [Not Available]. PMID- 26286077 TI - DEL-FINE: a new tool for assessing the delirogenic properties of drugs of relevance for European pharmacotherapy. AB - This article presents a list of potentially delirogenic properties of drugs that are currently of relevance to drug therapy in Europe, which was created through a Delphi process including experts from professions relevant to diagnosis and treatment of delirium. The Diagnostic and Statistical Manual of Mental Disorders 5 (DSM 5) defines delirium as a disturbance in attention, awareness and cognition that develops over a short period of time and fluctuates. Possible causes of delirium are manifold: usually delirium is considered to develop in a multifactorial way, caused by inalterable parameters, such as advanced age and pre-existing cognitive impairment and precipitated by modifiable parameters, such as the use of certain drugs or substance withdrawal. Delirium is a serious condition with a pronounced impact on morbidity, mortality and costs to the healthcare system. Circumstances and drugs that might precipitate or worsen delirium should therefore be avoided whenever possible. A list of drugs that might have a detrimental influence on the emergence and duration of delirium has been created using the terms "delirogenity" and "delirogenic" to describe the potential of a drug or withdrawal to cause or worsen delirium. The results are novel and noteworthy, as their focus is on substances relevant to European pharmacotherapy. Furthermore, they represent a methodical consensus from a group of experts of a wide variety of professions relevant to the prevention, diagnosis and treatment of delirium, such as nursing, pharmacy, pharmacology, surgical and internal medicine, neurology, psychiatry, intensive care and medicine, with working, teaching and scientific experience in several European countries practicing both in primary and secondary care. PMID- 26286079 TI - Family Functioning in First-Episode and Chronic Psychosis: The Role of Patient's Symptom Severity and Psychosocial Functioning. AB - The aim of the present study was to assess the relationship between illness related characteristics, such as symptom severity and psychosocial functioning, and specific aspects of family functioning both in patients experiencing their first episode of psychosis (FEP) and chronically ill patients. A total of 50 FEP and 50 chronic patients diagnosed with schizophrenia or bipolar disorder (most recent episode manic severe with psychotic features) and their family caregivers participated in the study. Family functioning was evaluated in terms of cohesion and flexibility (FACES IV Package), expressed emotion (FQ), family burden (FBS) and caregivers' psychological distress (GHQ-28). Patients' symptom severity (BPRS) and psychosocial functioning (GAS) were assessed by their treating psychiatrist within 2 weeks from the caregivers' assessment. Increased symptom severity was associated with greater dysfunction in terms of family cohesion and flexibility (beta coefficient -0.13; 95 % CI -0.23, -0.03), increased caregivers' EE levels on the form of emotional overinvolvement (beta coefficient 1.03; 95 % CI 0.02, 2.03), and psychological distress (beta coefficient 3.37; 95 % CI 1.29, 5.45). Family burden was found to be significantly related to both symptom severity (beta coefficient 3.01; 95 % CI 1.50, 4.51) and patient's functioning (beta coefficient -2.04; 95 % CI -3.55, -0.53). No significant interaction effect of chronicity was observed in the afore-mentioned associations. These findings indicate that severe psychopathology and patient's low psychosocial functioning are associated with poor family functioning. It appears that the effect for family function is significant from the early stages of the illness. Thus, early psychoeducational interventions should focus on patients with severe symptomatology and impaired functioning and their families. PMID- 26286080 TI - Eating Disorders in Lebanon: Directions for Public Health Action. AB - Research in the field of eating disorders (ED) is limited in the Middle East. The aim of the present study was to profile Lebanese ED outpatients. A mixed-method design was used. Clinicians across Lebanon filled individual questionnaires about their 2013 ED outpatients (n = 104) and participated in focus groups. Results showed that bulimia nervosa was the most prevalent ED (46.1 %) followed by anorexia nervosa (39.4 %) and binge eating (14.4 %). The emerging socio demographic profile of the Lebanese ED patient was that of a single female young adult of middle to high socio-economic status with severe ED symptoms (amenorrhea, multiple purging behaviors) and depression. Also, there was a general delay in seeking help which made patient recovery more difficult. The present study emphasizes the critical need for a public health approach to ED awareness and could help in developing preventive and remedial educational programs targeting youth in Lebanon and the Middle East. PMID- 26286081 TI - Mental Health Beliefs Amongst Emirati Female College Students. AB - Recent epidemiological data from Arabian Gulf nations suggest that mental health problems such as depression and anxiety have a relatively high prevalence, particularly amongst women. However, despite the widespread morbidity, treatment seeking for mental health problems is low. Mental health beliefs amongst female Emirati college students were explored. A questionnaire exploring perceptions about the causes, consequences and best forms of intervention for mental health problems was administered to 70 participants. Data revealed that social and environmental factors were given the most weight in terms of etiology. Social stigma was the most frequently identified barrier to help seeking. Religious practices were commonly reported as an approach to cope with mental health problems and to maintain good psychological health. Most participants reported willingness to seek help from a healthcare professional. Results are discussed in terms of their implications for improving the quality and accessibility of mental health services in the gulf region. PMID- 26286083 TI - Predicting Thermodynamic Behaviors of Non-Protein Amino Acids as a Function of Temperature and pH. AB - Why does life use alpha-amino acids exclusively as building blocks of proteins? To address that fundamental question from an energetic perspective, this study estimated the standard molal thermodynamic data for three non-alpha-amino acids (beta-alanine, gamma-aminobutyric acid, and epsilon-aminocaproic acid) and alpha amino-n-butyric acid in their zwitterionic, negative, and positive ionization states based on the corresponding experimental measurements reported in the literature. Temperature dependences of their heat capacities were described based on the revised Helgeson-Kirkham-Flowers (HKF) equations of state. The obtained dataset was then used to calculate the standard molal Gibbs energies (?G (o)) of the non-alpha-amino acids as a function of temperature and pH. Comparison of their ?G (o) values with those of alpha-amino acids having the same molecular formula showed that the non-alpha-amino acids have similar ?G (o) values to the corresponding alpha-amino acids in physiologically relevant conditions (neutral pH, <100 degrees C). In acidic and alkaline pH, the non-alpha-amino acids are thermodynamically more stable than the corresponding alpha-ones over a broad temperature range. These results suggest that the energetic cost of synthesis is not an important selection pressure to incorporate alpha-amino acids into biological systems. PMID- 26286082 TI - Low CD1c + myeloid dendritic cell counts correlated with a high risk of rapid disease progression during early HIV-1 infection. AB - BACKGROUND: During early HIV-1 infection (EHI), the interaction between the immune response and the virus determines disease progression. Although CD1c + myeloid dendritic cells (mDCs) can trigger the immune response, the relationship between CD1c + mDC alteration and disease progression has not yet been defined. METHODS: EHI changes in CD1c + mDC counts, surface marker (CD40, CD86, CD83) expression, and IL-12 secretion were assessed by flow cytometry in 29 patients. RESULTS: When compared with the normal controls, patients with EHI displayed significantly lower CD1c + mDC counts and IL-12 secretion and increased surface markers. CD1c + mDC counts were positively correlated with CD4+ T cell counts and inversely associated with viral loads. IL-12 secretion was only positively associated with CD4+ T cell counts. Rapid progressors had lower counts, CD86 expression, and IL-12 secretion of CD1c + mDCs comparing with typical progressors. Kaplan-Meier analysis and Cox regression models suggested patients with low CD1c + mDC counts (<10 cells/MUL) had a 4-fold higher risk of rapid disease progression than those with high CD1c + mDC counts. However, no relationship was found between surface markers or IL-12 secretion and disease progression. CONCLUSIONS: During EHI, patients with low CD1c + mDC counts were more likely to experience rapid disease progression than those with high CD1c + mDC counts. PMID- 26286084 TI - Timescales of Oxygenation Following the Evolution of Oxygenic Photosynthesis. AB - Among the most important bioenergetic innovations in the history of life was the invention of oxygenic photosynthesis-autotrophic growth by splitting water with sunlight-by Cyanobacteria. It is widely accepted that the invention of oxygenic photosynthesis ultimately resulted in the rise of oxygen by ca. 2.35 Gya, but it is debated whether this occurred more or less immediately as a proximal result of the evolution of oxygenic Cyanobacteria or whether they originated several hundred million to more than one billion years earlier in Earth history. The latter hypothesis involves a prolonged period during which oxygen production rates were insufficient to oxidize the atmosphere, potentially due to redox buffering by reduced species such as higher concentrations of ferrous iron in seawater. To examine the characteristic timescales for environmental oxygenation following the evolution of oxygenic photosynthesis, we applied a simple mathematical approach that captures many of the salient features of the major biogeochemical fluxes and reservoirs present in Archean and early Paleoproterozoic surface environments. Calculations illustrate that oxygenation would have overwhelmed redox buffers within ~100 kyr following the emergence of oxygenic photosynthesis, a geologically short amount of time unless rates of primary production were far lower than commonly expected. Fundamentally, this result arises because of the multiscale nature of the carbon and oxygen cycles: rates of gross primary production are orders of magnitude too fast for oxygen to be masked by Earth's geological buffers, and can only be effectively matched by respiration at non-negligible O2 concentrations. These results suggest that oxygenic photosynthesis arose shortly before the rise of oxygen, not hundreds of millions of years before it. PMID- 26286085 TI - Infantile encephalitic beriberi: magnetic resonance imaging findings. AB - BACKGROUND: Thiamine deficiency in infants is still encountered in developing countries. It may present with acute neurological manifestations of infantile encephalitic beriberi. OBJECTIVE: To review brain MRI findings in infantile encephalitic beriberi from a single institution. MATERIALS AND METHODS: A retrospective review of MRI scans in 22 infants with acute-onset beriberi encephalopathy was carried out. RESULTS: Hyperintense lesions on T2-weighted images were seen symmetrically in the putamen in all patients, in the caudate nuclei in 16/22 (73%), the thalami in 7/22 (32%) and the globi pallidi in 3/22 (14%) of the infants. Altered signal intensity lesions in the cerebral cortex were seen in 7/22 (32%). The mammillary bodies were seen in one infant and the periaqueductal gray matter in two. There was restricted diffusion in 14/22 (64%), and 6/8 children with no evidence of restriction had been imaged >=10 days after presentation. MR spectroscopy showed increased lactate peak in 6/8 infants (75%). CONCLUSION: Recognition of symmetrical T2-W hyperintense lesions in the basal ganglia with restricted diffusion and prominent lactate peak may allow early diagnosis of encephalitic beriberi in at-risk infants. PMID- 26286087 TI - Authors' reply to Lewis and Bray. PMID- 26286086 TI - EGFR Kinase Domain Duplication (EGFR-KDD) Is a Novel Oncogenic Driver in Lung Cancer That Is Clinically Responsive to Afatinib. AB - Oncogenic EGFR mutations are found in 10% to 35% of lung adenocarcinomas. Such mutations, which present most commonly as small in-frame deletions in exon 19 or point mutations in exon 21 (L858R), confer sensitivity to EGFR tyrosine kinase inhibitors (TKI). In analyzing the tumor from a 33-year-old male never-smoker, we identified a novel EGFR alteration in lung cancer: EGFR exon 18-25 kinase domain duplication (EGFR-KDD). Through analysis of a larger cohort of tumor samples, we detected additional cases of EGFR-KDD in lung, brain, and other cancers. In vitro, EGFR-KDD is constitutively active, and computational modeling provides potential mechanistic support for its auto-activation. EGFR-KDD-transformed cells are sensitive to EGFR TKIs and, consistent with these in vitro findings, the index patient had a partial response to the EGFR TKI afatinib. The patient eventually progressed, at which time resequencing revealed an EGFR-dependent mechanism of acquired resistance to afatinib, thereby validating EGFR-KDD as a driver alteration and therapeutic target. SIGNIFICANCE: We identified oncogenic and drug-sensitive EGFR-KDD that is recurrent in lung, brain, and soft-tissue cancers and documented that a patient with metastatic lung adenocarcinoma harboring the EGFR-KDD derived significant antitumor response from treatment with the EGFR inhibitor afatinib. Findings from these studies will be immediately translatable, as there are already several approved EGFR inhibitors in clinical use. PMID- 26286088 TI - Characterization of a novel alkaline arylsulfatase from Marinomonas sp. FW-1 and its application in the desulfation of red seaweed agar. AB - A bacterial strain capable of hydrolyzing sulfate ester bonds of p-nitrophenyl sulfate (pNPS) and agar was isolated from the coast area of Qingdao, China. It was identified as Marinomonas based on its 16S rRNA gene sequence and named as Marinomonas sp. FW-1. An arylsulfatase with a recovery of 13 % and a fold of 12 was purified to a homogeneity using ion exchange and gel filtration chromatographies. The enzyme was composed of a single polypeptide chain with the molecular mass of 33 kDa estimated using SDS-PAGE. The optimal pH and temperature of arylsulfatase were pH 9.0 and 45, respectively. Arylsulfatase was stable over pH 8-11 and at temperature below 55 degrees C. The K m and V max of this enzyme for the hydrolysis of pNPS were determined to be 13.73 and 270.27 MUM/min, respectively. The desulfation ratio against agar from red seaweed Gelidium amansii and Gracilaria lemaneiformis were 86.11 and 89.61 %, respectively. There was no difference between the DNA electrophoresis spectrum on the gel of the arylsulfatase-treated G. amansii agar and that of the commercial agarose. Therefore, this novel alkaline arylsulfatase might have a great potential for application in enzymatic conversion of agar to agarose. PMID- 26286089 TI - A validated, risk assessment tool for predicting readmission after open ventral hernia repair. AB - BACKGROUND/PURPOSE: To present a validated model that reliably predicts unplanned readmission after open ventral hernia repair (open-VHR). STUDY DESIGN: A total of 17,789 open-VHR patients were identified using the 2011-2012 ACS-NSQIP databases. This cohort was subdivided into 70 and 30% random testing and validation samples, respectively. Thirty-day unplanned readmission was defined as unexpected readmission for a postoperative occurrence related to the open-VHR procedure. Independent predictors of 30-day unplanned readmission were identified using multivariable logistic regression on the testing sample (n = 12,452 patients). Subsequently, the predictors were weighted according to beta-coefficients to generate an integer-based Clinical Risk Score (CRS) predictive of readmission, which was validated using receiver operating characteristics (ROC) analysis of the validation sample (n = 5337 patients). RESULTS: The rate of 30-day unplanned readmission was 4.7%. Independent risk factors included inpatient status at time of open-VHR, operation time, enterolysis, underweight, diabetes, preoperative anemia, length of stay, chronic obstructive pulmonary disease, history of bleeding disorders, hernia with gangrene, and panniculectomy (all P < 0.05). ROC analysis of the validation cohort rendered an area under the curve of 0.71, which demonstrates the accuracy of this prediction model. Predicted incidence within each 5 risk strata was statistically similar to the observed incidence in the validation sample (P = 0.18), further highlighting the accuracy of this model. CONCLUSION: We present a validated risk stratification tool for unplanned readmissions following open-VHR. Future studies should determine if implementation of our CRS optimizes safety and reduces readmission rates in open VHR patients. PMID- 26286093 TI - Management of Relapsed/Refractory Acute Myeloid Leukemia in the Elderly: Current Strategies and Developments. AB - Elderly patients with acute myeloid leukemia (AML) who are refractory to or relapse following frontline treatment constitute a poor-risk group with a poor long-term outcome. Host-related factors and unfavorable disease-related features contribute to early treatment failures following frontline therapy, thus making attainment of remission and long-term survival with salvage therapy particularly challenging for elderly patients. Currently, no optimal salvage strategy exists for responding patients, and allogeneic hematopoietic stem cell transplant is the only curative option in this setting; however, the vast majority of elderly patients are not candidates for this procedure due to poor functional status secondary to age and age-related comorbidities. Furthermore, the lack of effective salvage programs available for elderly patients with recurrent AML underscores the need for therapies that consistently yield durable remissions or durable control of their disease. The purpose of this review was to highlight the currently available strategies, as well as future strategies under development, for treating older patients with recurrent AML. PMID- 26286094 TI - Effect of Angiotensin-Converting Enzyme Inhibitors on Physical Function in Elderly Subjects: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Sarcopenia has been accepted as a new geriatric syndrome, which will become a common and important public health challenge. And angiotensin-converting enzyme inhibitors (ACEIs) have been shown to improve exercise capacity in elderly without heart failure. OBJECTIVES: To evaluate the effect of angiotensin converting enzyme inhibitors (ACEIs) on physical function in elderly. DATA SOURCES: The Cochrane Library, PubMed, EMBASE and Web of Science were searched. ELIGIBILITY CRITERIA: All researches included were randomized controlled trials (RCTs) which compared any kind of ACEIs with placebo or other anti-hypertensives in elderly, and provided empirical data of grip strength and 6-min walk distance change from baseline. STUDY APPRAISAL AND SYNTHESIS METHODS: Risk of bias was systematically assessed by using the Cochrane risk of bias tool. Data of grip strength and 6-min walk distance change from baseline were collected and mean differences (MDs) were calculated along with 95% CI (confidence interval) by using a random effects model. RESULTS: In 3 RCTs including 337 elderly participants, ACEIs (n = 178) did not significantly improved 6-min walk distance (13.45, 95% CI: -16.71 to 43.61; P = 0.38) versus placebo or other antihypertensives (n = 159). In 3 RCTs including 499 elderly participants, grip strength was not significantly different (-0.67, 95% CI: -1.53 to 0.19; P = 0.12) between ACEIs (n = 260) and placebo or other antihypertensives (n = 239). LIMITATIONS: There exists only 4 RCTs and the number of participants is limited. Pooling of data were from different trials including different participant characteristics. And intervention is not strictly consistent. CONCLUSION: This study shows that ACEIs can not significantly improve walk distance or the age related decline of muscle strength for older participants in clinical trials. PMID- 26286095 TI - Adaptation to an autoimmune disorder: Does mental flexibility impact illness related self-regulation? AB - OBJECTIVE: To examine whether mental flexibility moderates the relationship between illness representations of control and coping behaviour in individuals suffering from rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). DESIGN: Recently, diagnosed RA (N = 80) and SLE (N = 75) patients completed questionnaires about illness representations of personal and treatment control and four coping behaviours: instrumental coping, adherence to medical advice, palliative coping and wishful thinking. Mental flexibility was assessed with the Trail Making Test Part B (TMT-B), while visuomotor processing speed, as a confounder, was assessed with the Trail Making Test Part A (TMT-A). Moderated mediation models were tested within a bootstrapped multiple regression framework. RESULTS: TMT-A scores had no statistically significant moderation effects on the relation between representations and coping behaviour. Conversely, in those participants with SLE, TMT-B scores moderated the relation of personal control to wishful thinking and palliative coping, as well as the relation of treatment control to both wishful thinking and palliative coping. All significant effects were restricted to the SLE group. CONCLUSION: Interactions between neurocognitive factors and the process of illness adaptation may emerge early during the course of SLE. The present findings highlight the role of cognitive functioning as an integral part of the illness-related self-regulation mechanism. PMID- 26286096 TI - Leukocyte Telomere Length and Cancer Risk: A Dynamic Problem. PMID- 26286097 TI - Septo-optic dysplasia: Magnetic Resonance Imaging findings. AB - Septo-optic dysplasia is a rare congenital disorder involving brain and optic pathways. We present typical Magnetic Resonance Imaging (MRI) findings of a case of Septo-optic dysplasia in a 19 year old female patient. PMID- 26286098 TI - Collapsed neonate? Cause. PMID- 26286099 TI - ReCAP: Feasibility and Effectiveness of a Pilot Program to Facilitate Quality Improvement Learning in Oncology: Experience of the American Society of Clinical Oncology Quality Training Program. AB - PURPOSE: Studies have demonstrated that structured training programs can improve health professionals' skills in performing clinical care or research. We sought to develop and test a novel quality training program (QTP) tailored to oncology clinicians. METHODS: The American Society of Clinical Oncology QTP consisted of three in-person learning sessions and four phases: prework, planning, implementation, and sustain and spread. We measured two primary outcomes: program feasibility and effectiveness. Feasibility was evaluated by recording participation. Effectiveness was measured using the Kirkpatrick model, which evaluates four outcomes: reaction, learning, behavior, and results. We collected qualitative feedback through a focus group of participants and mixed quantitative qualitative results from a 6-month follow-up evaluation survey. Results are presented using descriptive statistics. RESULTS: We received feedback from of 80% of participants who took part in 92% of in-person program days. QTP deliverables were completed by 100% of teams; none withdrew from the program. Regarding reaction, 100% of respondents expressed interest in actively contributing to future QTP courses. For learning, most teams continued to use the core methodology tools (eg, project charter, aims statements) after the program. Regarding behavior, when asked about intention to serve as a local quality improvement leader, a majority said they "definitely will" serve as: team leader on a specific project (75%), project champion or sponsor (75%), or teacher or trainer for others (64%). In evaluating outcomes, 50% reported applying learned methodology to new projects at their local institution. CONCLUSION: We demonstrate one of the first feasible and effective training programs to facilitate quality improvement learning for oncology clinicians. PMID- 26286101 TI - Genomic insights into the early-diverging magnetotactic bacteria. PMID- 26286100 TI - Health-Related Quality of Life of Food-Insecure Ethnic Minority Patients With Cancer. AB - PURPOSE: The association between food insecurity and health-related quality of life (QOL) of racial/ethnic minority patients with cancer has not been examined. The purpose of this study is to determine the relationship between food insecurity and health-related QOL reported by racial/ethnic minority patients with cancer. METHODS: A consecutive sample of 1,390 underserved ethnic minority patients receiving cancer care in 10 cancer clinics and hospitals in New York City participated in this study. Health-related QOL was measured by the Functional Assessment of Cancer Therapy-General (FACT-G) and food security was assessed by the US Department of Agriculture Core Food Security Module. RESULTS: Of the 1,390 patients, 581 (41.8%) were classified as food secure, 571 (41.1%) with low food security, and 238 (17.1%) with very low food security. Health related QOL decreased with each lower food security level. Patient self-reported physical, functional, social, and emotional well-being subscale scores decrease significantly with increasing food insecurity. After controlling for demographic and medical-related factors, the decreases in QOL, physical, functional, social and emotional well-being scores with increasing food insecurity remained significant. CONCLUSION: Food insecurity was associated with lower QOL in this sample of underserved racial/ethnic minority patients with cancer. Underserved ethnic minority patients diagnosed with cancer are a vulnerable patient population, at significant risk for inadequate food access and the related lower QOL. PMID- 26286102 TI - CSF N-glycan profile reveals sialylation deficiency in a patient with GM2 gangliosidosis presenting as childhood disintegrative disorder. AB - Protein N-glycosylation consists in the synthesis and processing of the oligosaccharide moiety (N-glycan) linked to a protein and it serves several functions for the proper central nervous system (CNS) development and function. Previous experimental and clinical studies have shown the importance of proper glycoprotein sialylation for the synaptic function and the occurrence of autism spectrum disorders (ASD) in the presence of sialylation deficiency in the CNS. Late-onset Tay Sachs disease (LOTSD) is a lysosomal disorder caused by mutations in the HEXA gene resulting in GM2-ganglioside storage in the CNS. It is characterized by progressive neurological impairment and high co-occurrence of psychiatric disturbances. We studied the N-glycome profile of the cerebrospinal fluid (CSF) in a 14 year-old patient with GM2-gangliosidosis (LOTSD). At the age of 4, the patient presented regressive autism fulfilling criteria for childhood disintegrative disorder (CDD). A CSF sample was obtained in the course of diagnostic work-up for the suspicion of an underlying neurodegenerative disorder. We found definite changes of CSF N-glycans due to a dramatic decrease of sialylated biantennary and triantennary structures and an increase of asialo-core fucosylated bisected N-glycans. No changes of total plasma N-glycans were found. Herein findings highlight possible relationships between the early onset psychiatric disturbance featuring CDD in the patient and defective protein sialylation in the CNS. In conclusion, the study first shows aberrant N-glycan structures of CSF proteins in LOTSD; unveils possible pathomechanisms of GM2 gangliosidosis; supports existing relationships between neuropsychiatric disorders and unproper protein glycosylation in the CNS. PMID- 26286103 TI - The Wild West: Associations between mining and violence in Western Australia. AB - OBJECTIVE: To investigate the association between mining activity and police reported assault offences across Western Australia. DESIGN: A cross-sectional multivariable negative binomial regression analysis at the local government area level. SETTING: Local government areas in Western Australia. PARTICIPANTS: Victims of reported assault offences occurring in 2008-2009. MAIN OUTCOME MEASURES: Eight reported assault measures by gender of victim and type of assault. The analysis controlled for a range of potentially confounding variables, including numbers of licensed outlets and alcohol sales. RESULTS: Compared with females in other areas, females in mining regions had a 64% increased risk of assault, a 59% increased risk of non-domestic assault and a 136% increased risk of sexual assault. Risk of domestic assault was 64% higher for males in mining regions. CONCLUSIONS: Regions where mining is a major employer of people usually or temporarily residing in the area (i.e. usual residents or temporary fly-in fly-out residents) are associated with higher risk of assaults among females and domestic assaults among males, and these associations appear to be independent of licensed outlet numbers and alcohol sales. Mining communities appear to present a special case for the management and reduction of violence; public health and safety intervention needs to identify and address risk factors independent of alcohol use. PMID- 26286104 TI - Fast, sensitive and specific diagnosis of infections with Leishmania spp. in formalin-fixed, paraffin-embedded skin biopsies by cytochrome b polymerase chain reaction. AB - BACKGROUND: Northern spread of sandflies and Leishmania spp. has been observed in Europe. Diagnosis can be difficult owing to the various clinical manifestations. Species identification is important for patient management and therapy. Molecular diagnostics is increasingly used for pan-Leishmania detection but species identification remains challenging in formalin-fixed material. OBJECTIVES: To apply cytochrome b (cytb) polymerase chain reaction (PCR) and sequencing for identification of Leishmania species on formalin-fixed, paraffin-embedded (FFPE) skin biopsies; and to identify species-specific histological patterns. METHODS: Sixty-nine biopsies (48 patients) diagnosed with leishmaniasis based on the presence of amastigotes in the tissue (n = 41) or granulomatous infiltrates with positive pan-Leishmania real-time PCR (n = 28) were analysed with cytb PCR, sequencing and phylogenetic analysis. Histological sections were analysed; epidemiological data were collected. RESULTS: Cytb PCR identified Leishmania in all specimens: L. infantum (79%), L. major (8%), L. panamensis (4%), L. tropica (4%), L. killicki (2%) and L. aethiopica (2%). Of the detected species 95% were endemic to the country in which the infection was acquired. Amastigotes were found in 59%. Infiltrates were mainly tuberculoid granulomatous (65%), interstitial (15%) and sarcoidal (10%). Pseudolymphomatous features and pseudocarcinomatous hyperplasia were more common in L. major infections than in L. infantum (P < 0.01). CONCLUSIONS: Cytb PCR and sequencing is a fast, reliable and sensitive assay for identification of Leishmania spp. in FFPE biopsies. Leishmania infantum is the main cause of cutaneous leishmaniasis in Germany. Tuberculoid granulomas, other types of granulomas and pseudolymphomatous infiltrates may be encountered; the latter being indicative of infection with L. major. PMID- 26286105 TI - Case formulation in clinical practice: Associations with psychological mindedness, attachment and burnout in staff working with people experiencing psychosis. AB - OBJECTIVES: Case formulation can impact on therapeutic relationships, staff understanding and outcomes, which might be particularly important when working with complex mental health problems such as psychosis. However, the evidence base is equivocal and there is insufficient understanding around the staff-related factors that influence effective psychological case formulation. This study investigated the influence of staff characteristics (both professional and personal) on case formulation skill. DESIGN: This was a cross-sectional study, with all of the measures collected at the same time point. METHODS: Fifty staff members working on inpatient wards with individuals experiencing psychosis were recruited. Measures included independently rated case formulation skill and psychological mindedness (the ability to draw together aspects of thoughts, feelings and actions), both in relation to hypothetical cases. Self-report questionnaires assessed psychological mindedness, attachment styles, symptoms of burnout and professional qualifications. RESULTS: The preliminary analyses indicated that case formulation skill was associated with higher psychological mindedness (both self-reported and independently-rated) and lower levels of avoidant attachment styles. Simultaneous entry multiple regression demonstrated that the only independent predictor of case formulation skill was independently rated psychological mindedness. CONCLUSIONS: These findings highlight the factors that contribute to staff's ability to case formulate and the possibility for services to develop psychological mindedness and case formulation skills through formal training, alongside fostering a psychological minded working environment. PRACTITIONER POINTS: Case formulation skill is positively associated with the personal ability (or inclination) to draw together aspects of experience in a psychological manner (i.e., psychological mindedness) It might also be important to consider avoidant attachment tendencies in relation to formulation skills The sample was relatively small and drawn from a limited number of services, which might reduce the generalizability of the findings Psychological mindedness might not be captured adequately by self-report tools and services may wish to employ more novel ways of assessing this important skill in staff groups (such as the speech sample used in the current study). PMID- 26286106 TI - Tissue-engineered tubular substitutions for urinary diversion in a rabbit model. AB - Clinically, autologous gastrointestinal segments are traditionally used for urinary diversion. However, this procedure often causes many serious complications. Tissue engineering may provide an alternative treatment method in urinary diversion. This research aims to produce tissue-engineered tubular substitutions by using homologous adipose-derived stem cells, smooth muscle cells, and bladder acellular matrix in developing urinary diversion in a rabbit model. Adipose-derived stem cells and smooth muscle cells of rabbit were obtained and cultured in vitro. These cultured adipose-derived stem cells and smooth muscle cells were seeded onto the two sides of the bladder acellular matrix and then incubated for seven days. The cell-seeded matrix was used to build tissue engineered tubular substitutions, which were then implanted and wrapped into the omentum in vivo for two weeks to promote angiogenesis. In the experimental group, the bladder of 20 rabbits was totally resected, and the above tissue-engineered tubular substitutions were used for urinary diversion. In the control group, bladder acellular matrix tubular substitutions with unseeded cells were implanted into the omentum and were used as urinary diversion on another five rabbits with the same process. The implants were harvested, and histological examination was conducted at 2, 4, 8, and 16 weeks after operation. Intravenous urography assessment was performed at 16 weeks postoperatively. All the rabbits were alive in the experimental group until they were sacrificed. Histological analysis of the construct displayed the presence of multilayer urothelial cells on the luminal side and organized smooth muscle tissue on the other side, and different diameters of neovascularization were clearly identified in the substitutions obtained. No leakage, stricture, or obstructions were noted with intravenous urography assessment. All the animals in the control group died within two weeks, and urine leakage, scar formation, and inflammation were detected through autopsy. This study demonstrates the feasibility of tissue-engineered tubular substitutions constructed using homologous adipose-derived stem cells, smooth muscle cells, and bladder acellular matrix for urinary diversion in a rabbit model. PMID- 26286108 TI - Effects of Hydrogen Peroxide and Metrifonate on Monogenean ligictaluridus floridanus on Catfish ( Ictalurus punctatus , Rafinesque) Gills. AB - Hydrogen peroxide (H2O2) and metrifonate (Mtf) are common products used in ectoparasite infestations on fish cultures. The therapeutic efficacy of H2O2 and Mtf on a common monogenean parasite, Ligictaluridus floridanus, was evaluated in channel catfish ( Ictalurus punctatus ). In vitro trials were conducted using excised fish gills naturally infected with L. floridanus, which were immersed in H2O2 (150, 300, and 570 mg L(-1)) and Mtf (0.25, 0.5, and 0.75 mg L(-1)) solutions. The efficacy of the treatments was based on the survival time of the parasites, observed microscopically. In addition, an in vivo trial using catfish juveniles, naturally infected with L. floridanus, was also performed. One group received immersion baths of 570 mg L(-1) H2O2 (3%) during 4 min; the Mtf (90%) group received 0.5 mg L(-1) Mtf for 10 min. Treatments were done on days 3, 7, and 11 of the experiment. Results indicate that baths with Mtf do not significantly reduce the mean intensity of the parasite per gill arch, nor do they reduce the in vitro survival time of parasites during treatment; H2O2 baths at 570 mg L(-1) during 4 min were effective (P < 0.05) against adult and juvenile stages of L. floridanus. This study supports the use of H2O2 as an effective antiparasitic agent against I. punctatus . PMID- 26286109 TI - The cricothyroid joint in elderly Japanese individuals. AB - Using 15 cricothyroid joint (CT joint) specimens obtained from donated cadavers of elderly individuals, we examined the morphologies of the ceratocricoid ligaments as well as the synovial tissue. The ligaments consistently contained abundant elastic fibers: the fibers tended to be straight on the anterior side in contrast to a mesh-like arrangement on the posterior side. Thick and/or long synovial folds were often evident in the CT joint. The synovial tissue usually contained CD68-positive macrophages, but the positive cells were often restricted to certain parts of the tissue. Factor VIII-positive capillaries were present but few in number, and CD3- or IgM-positive lymphocytes were absent in the synovial tissue. Degenerative changes in the joint cartilage, such as roughness or thinning, were often present, but no cartilage defects were evident. Therefore, in contrast to the small, non-weight-bearing joints of the musculoskeletal system, we considered the degeneration of the CT joint to be a specific, silent form of osteoarthritis. For high-pitched phonation and ossification of the laryngeal cartilage, the CT joint in elderly individuals seemed to maintain its anterior gliding and rotation with the aid of elastic fiber-rich tissues compensating for the loss of congruity between the joint cartilage surfaces. PMID- 26286107 TI - A novel dopamine transporter transgenic mouse line for identification and purification of midbrain dopaminergic neurons reveals midbrain heterogeneity. AB - Midbrain dopaminergic (DAergic) neurons are a heterogeneous cell group, composed of functionally distinct cell populations projecting to the basal ganglia, prefrontal cortex and limbic system. Despite their functional significance, the midbrain population of DAergic neurons is sparse, constituting only 20 000-30 000 neurons in mice, and development of novel tools to identify these cells is warranted. Here, a bacterial artificial chromosome mouse line [Dat1-enhanced green fluorescent protein (eGFP)] from the Gene Expression Nervous System Atlas (GENSAT) that expresses eGFP under control of the dopamine transporter (DAT) promoter was characterized. Confocal microscopy analysis of brain sections showed strong eGFP signal reporter in midbrain regions and striatal terminals that co localized with the DAergic markers DAT and tyrosine hydroxylase (TH). Thorough quantification of co-localization of the eGFP reporter signal with DAT and TH in the ventral midbrain showed that a vast majority of eGFP-expressing neurons are DAergic. Importantly, expression profiles also revealed DAergic heterogeneity when comparing substantia nigra and ventral tegmental area. Dat1-eGFP mice showed neither change in synaptosomal DA uptake nor altered levels of DAT and TH in both striatum and midbrain. No behavioural difference between Dat1-eGFP and wild-type was found, suggesting that the strain is not aberrant. Finally, cell populations highly enriched in DAergic neurons can be obtained from postnatal mice by fluorescence-activated cell sorting and the sorted neurons can be cultured in vitro. The current investigation demonstrates that eGFP expression in this mouse line is selective for DAergic neurons, suggesting that the Dat1-eGFP mouse strain constitutes a promising tool for delineating new aspects of DA biology. PMID- 26286110 TI - Congenital malformations of the ureter: anatomical studies. AB - The ureter is a derivate of the Wolffian mesonephric duct and undergoes complex changes during development. The most common developmental anomaly is complete duplication of the ureter. Duplication of the ureter may be complete or incomplete. Incomplete duplication of ureter is well known as bifid ureter. Presence of various anomalies of the ureter is associated with increased risk of urinary tract infections and many other clinical complications. PMID- 26286111 TI - Added value of a single-energy projection-based metal-artifact reduction algorithm for the computed tomography evaluation of oral cavity cancers. AB - PURPOSE: The purpose of our study was to investigate the added value of the single-energy projection-based metallic artifact reduction (SEMAR) technique on the visualization and diagnostic confidence of oral cavity cancers. MATERIALS AND METHODS: Contrast-enhanced CT was performed on 40 patients with dental metalwork. Of these, 18 patients had pathologically confirmed oral cavity cancer, and the other 22 patients had no lesions. CT attenuation and noise in the oral cavity were compared between the conventional and SEMAR images. Two radiologists visually graded the diagnostic confidence on a 5-point scale from 1 (definitely absent) to 5 (definitely present). The value of the SEMAR was assessed in a receiver-operating characteristic curve analysis. RESULTS: The artifact of the SEMAR images was significantly lower than that of the conventional images (38.4 +/- 18.0 HU vs. 187.7 +/- 162.7 HU; P < 0.01). Reviewers 1 and 2 detected 10 and 7 more lesions with the SEMAR, respectively. Areas under the curve for the conventional and SEMAR reconstruction were 0.761 and 0.942, respectively, for reviewer 1 and 0.701 and 0.864, respectively, for reviewer 2. CONCLUSION: The SEMAR significantly improved the oral cavity cancer visualization and diagnostic confidence. PMID- 26286112 TI - Gene looping facilitates TFIIH kinase-mediated termination of transcription. AB - TFIIH is a general transcription factor with kinase and helicase activities. The kinase activity resides in the Kin28 subunit of TFIIH. The role of Kin28 kinase in the early steps of transcription is well established. Here we report a novel role of Kin28 in the termination of transcription. We show that RNAPII reads through a termination signal upon kinase inhibition. Furthermore, the recruitment of termination factors towards the 3' end of a gene was compromised in the kinase mutant, thus confirming the termination defect. A concomitant decrease in crosslinking of termination factors near the 5' end of genes was also observed in the kinase-defective mutant. Simultaneous presence of termination factors towards both the ends of a gene is indicative of gene looping; while the loss of termination factor occupancy from the distal ends suggest the abolition of a looped gene conformation. Accordingly, CCC analysis revealed that the looped architecture of genes was severely compromised in the Kin28 kinase mutant. In a looping defective sua7-1 mutant, even the enzymatically active Kin28 kinase could not rescue the termination defect. These results strongly suggest a crucial role of Kin28 kinase-dependent gene looping in the termination of transcription in budding yeast. PMID- 26286113 TI - Risk and management of venous thromboembolisms in bevacizumab-treated metastatic colorectal cancer patients. AB - PURPOSE: Bevacizumab may potentiate the risk of venous thromboembolisms (VTEs) in cancer patients, who are already predisposed to pro-thrombotic states. We aimed to characterize the incidence of VTEs in a population-based cohort of metastatic colorectal cancer (mCRC) patients treated with bevacizumab, describe patient and treatment factors associated with VTEs, and examine how VTEs are managed. METHODS: Patients diagnosed with mCRC from 2006 to 2009 and offered bevacizumab were included. Descriptive statistics were used to describe VTE occurrences and management. Univariate and multivariate regression models were constructed to explore associations between clinical factors and VTEs. RESULTS: We identified 541 mCRC patients: 27 never started bevacizumab and 15 were lost to follow-up. Of the 499 evaluable patients, median age was 61, 59.3% were men, 88.1% had ECOG 0/1, and 5.2% reported previous VTEs. Mean number of bevacizumab doses was 13.3 cycles. After receiving bevacizumab, 81 patients developed 93 cases of VTEs, with 9 patients experiencing >1 event. Individuals who experienced VTEs were more likely to have had pre-existing cardiovascular disease (OR 2.259, p = 0.0245), resection of primary cancer (OR 3.262, p = 0.0269), pre-chemotherapy platelet count >=350,000/MUL (OR 2.295, p = 0.0293), and received >12 bevacizumab cycles (OR 2.172, p = 0.0158). Use of bevacizumab varied after occurrence of VTE where it was discontinued in 34.4%, continued in 34.4%, and temporarily held in 1.1%. CONCLUSIONS: VTE risk can be high, especially in patients with specific pre treatment risk factors as well as in those who received more bevacizumab, suggesting a potential dose-related effect. Management of bevacizumab-related VTEs was variable. PMID- 26286114 TI - Alpha-ring Independent Assembly of the 20S Proteasome. AB - Archaeal proteasomes share many features with their eukaryotic counterparts and serve as important models for assembly. Proteasomes are also found in certain bacterial lineages yet their assembly mechanism is thought to be fundamentally different. Here we investigate alpha-ring formation using recombinant proteasomes from the archaeon Methanococcus maripaludis. Through an engineered disulfide cross-linking strategy, we demonstrate that double alpha-rings are structurally analogous to half-proteasomes and can form independently of single alpha-rings. More importantly, via targeted mutagenesis, we show that single alpha-rings are not required for the efficient assembly of 20S proteasomes. Our data support updating the currently held "alpha-ring first" view of assembly, initially proposed in studies of archaeal proteasomes, and present a way to reconcile the seemingly separate bacterial assembly mechanism with the rest of the proteasome realm. We suggest that a common assembly network underpins the absolutely conserved architecture of proteasomes across all domains of life. PMID- 26286115 TI - Improved survival in adult patients with acute lymphoblastic leukemia in the Netherlands: a population-based study on treatment, trial participation and survival. AB - This nationwide population-based study assessed trends in treatment, trial participation and survival among 1833 adult patients diagnosed with acute lymphoblastic leukemia (ALL) in the Netherlands between 1989 and 2012 reported to the Netherlands Cancer Registry. Patients were categorized into four periods and five age groups (18-24, 25-39, 40-59, 60-69 and ?70 years). The application of allogeneic stem cell transplantation (alloSCT), particularly reduced-intensity conditioning (RIC) alloSCT, increased over time up to age 70 years. The inclusion rate in the trials was 67, 66, 55, 58 and 0% for the five age groups. Survival improved over time for patients below 70 years. Five-year relative survival in the period 2007-2012 was 75, 57, 37, 22 and 5% for the five age groups. In that same period, 5-year overall survival among patients aged 18-39 years was 68% for the chemotherapy-alone group and 66% for the alloSCT group. For patients aged 40 69 years, the corresponding estimates were 24 and 41%. Pronounced survival improvement observed among patients aged 18-39 years might mainly be explained by implementation of pediatric-based regimens since 2005, whereas among patients aged 40-69 years, increased application of RIC-alloSCT has contributed significantly to the observed improvement. Outcome of patients aged ?70 remains unsatisfactory, indicating a need for specific trials for the elderly. PMID- 26286118 TI - Reply: Is the pot calling the kettle black? PMID- 26286116 TI - Blocking the ZZ domain of sequestosome1/p62 suppresses myeloma growth and osteoclast formation in vitro and induces dramatic bone formation in myeloma bearing bones in vivo. AB - We reported that p62 (sequestosome 1) serves as a signaling hub in bone marrow stromal cells (BMSCs) for the formation of signaling complexes, including NFkappaB, p38MAPK and JNK, that are involved in the increased osteoclastogenesis and multiple myeloma (MM) cell growth induced by BMSCs that are key contributors to multiple myeloma bone disease (MMBD), and demonstrated that the ZZ domain of p62 (p62-ZZ) is required for BMSC enhancement of MMBD. We recently identified a novel p62-ZZ inhibitor, XRK3F2, which inhibits MM cell growth and BMSC growth enhancement of human MM cells. In the current study, we evaluate the relative specificity of XRK3F2 for p62-ZZ, characterize XRK3F2's capacity to inhibit growth of primary MM cells and human MM cell lines, and test the in vivo effects of XRK3F2 in the immunocompetent 5TGM1 MM model. We found that XRK3F2 induces dramatic cortical bone formation that is restricted to MM containing bones and blocked the effects and upregulation of tumor necrosis factor alpha (TNFalpha), an osteoblast (OB) differentiation inhibitor that is increased in the MM bone marrow microenvironment and utilizes signaling complexes formed on p62-ZZ, in BMSC. Interestingly, XRK3F2 had no effect on non-MM bearing bone. These results demonstrate that targeting p62 in MM models has profound effects on MMBD. PMID- 26286119 TI - Is the pot calling the kettle black? PMID- 26286117 TI - Immunosuppressive human anti-CD83 monoclonal antibody depletion of activated dendritic cells in transplantation. AB - Current immunosuppressive/anti-inflammatory agents target the responding effector arm of the immune response and their nonspecific action increases the risk of infection and malignancy. These effects impact on their use in allogeneic haematopoietic cell transplantation and other forms of transplantation. Interventions that target activated dendritic cells (DCs) have the potential to suppress the induction of undesired immune responses (for example, graft versus host disease (GVHD) or transplant rejection) and to leave protective T-cell immune responses intact (for example, cytomegalovirus (CMV) immunity). We developed a human IgG1 monoclonal antibody (mAb), 3C12, specific for CD83, which is expressed on activated but not resting DC. The 3C12 mAb and an affinity improved version, 3C12C, depleted CD83(+) cells by CD16(+) NK cell-mediated antibody-dependent cellular cytotoxicity, and inhibited allogeneic T-cell proliferation in vitro. A single dose of 3C12C prevented human peripheral blood mononuclear cell-induced acute GVHD in SCID mouse recipients. The mAb 3C12C depleted CMRF-44(+)CD83(bright) activated DC but spared CD83(dim/-) DC in vivo. It reduced human T-cell activation in vivo and maintained the proportion of CD4(+) FoxP3(+) CD25(+) Treg cells and also viral-specific CD8(+) T cells. The anti-CD83 mAb, 3C12C, merits further evaluation as a new immunosuppressive agent in transplantation. PMID- 26286120 TI - Improved Techniques for Endoscopic Mucosal Resection (EMR) in Colorectal Adenoma. AB - BACKGROUND: Endoscopic therapy of colorectal adenomas and early cancers is a standard method. Besides oncological criteria, the method is limited by polyp location, size, and texture. METHOD: Based on the current literature, technical modifications and developments in endoscopic mucosal resection are described. RESULTS: Numerous approaches exist to improve the conditions of resection, including optimisation of mucosal elevation and modification of techniques, tools, and devices. CONCLUSION: Endoscopic therapy of sessile and flat colorectal polyps remains a challenge. Some of the presented modifications can help to address this challenge. PMID- 26286121 TI - Removal of oesophageal foreign bodies: comparison between oesophagoscopy and oesophagotomy in 39 dogs. AB - OBJECTIVES: To compare complication rates and outcomes after removal of oesophageal foreign bodies by endoscopy or by oesophagotomy. METHODS: Retrospective evaluation of medical records of dogs with oesophageal foreign bodies treated by endoscopy and/or oesophagotomy. Postoperative clinical signs, management, length of hospitalisation, type and rate of complications, and time interval to return to eating conventional diet were compared. RESULTS: Thirty nine dogs diagnosed with oesophageal foreign bodies between 1999 and 2011 were included in the study. Most common breeds included West Highland white terrier, Jack Russell terrier and shih-tzu. Successful endoscopic removal was possible in 24 out of 32 cases (Group 1), while surgical removal was successful in 15 out of 15 cases (7 of which had unsuccessful attempts at endoscopic removal) (Group 2). Length of hospitalisation, time to removal of gastrostomy tube and time to eat conventional diet did not differ between the groups. After foreign body removal, the incidence of oesophagitis, oesophageal stricture and perforation observed during repeated endoscopy were similar between the groups. CLINICAL SIGNIFICANCE: In this retrospective study, removal of oesophageal foreign bodies either by oesophagoscopy or oesophagotomy had a similar outcome. PMID- 26286122 TI - Ir(III)-Catalyzed Oxidative Coupling of NH Isoquinolones with Benzoquinone. AB - The oxidative coupling reactions of NH isoquinolones with 1,4-benzoquinone proceeded efficiently to form spiro compounds in the presence of an Ir(III) catalyst through C-H activation. The reactions have a broad range of substrates, with nearly quantitative yields, without the use of external oxidants. For 1,4 naphthoquinone and other substituted 1,4-benzoquinone substrates the reactions also gave high yields with Cu(OAc)2.H2O as an external oxidant. A catalytically competent five-membered iridacycle has been isolated and structurally characterized, thus revealing a key intermediate in the catalytic cycle. PMID- 26286123 TI - A Branching Process to Characterize the Dynamics of Stem Cell Differentiation. AB - The understanding of the regulatory processes that orchestrate stem cell maintenance is a cornerstone in developmental biology. Here, we present a mathematical model based on a branching process formalism that predicts average rates of proliferative and differentiative divisions in a given stem cell population. In the context of vertebrate neurogenesis, the model predicts complex non-monotonic variations in the rates of pp, pd and dd modes of division as well as in cell cycle length, in agreement with experimental results. Moreover, the model shows that the differentiation probability follows a binomial distribution, allowing us to develop equations to predict the rates of each mode of division. A phenomenological simulation of the developing spinal cord informed with the average cell cycle length and division rates predicted by the mathematical model reproduces the correct dynamics of proliferation and differentiation in terms of average numbers of progenitors and differentiated cells. Overall, the present mathematical framework represents a powerful tool to unveil the changes in the rate and mode of division of a given stem cell pool by simply quantifying numbers of cells at different times. PMID- 26286124 TI - Does follow-up offer the best quality of life for patients affected by so-called 'giant' haemangiomas of the liver? PMID- 26286126 TI - Tumour, Oxidative Stress and Host T Cell Response: Cementing the Dominance. AB - Reactive oxygen species (ROS) and free radicals are produced intrinsically during normal cellular metabolic processes or extrinsically due to ionizing radiations, UV rays, xenobiotic insult, etc. ROS are important signal mediators and are used by the immune system to destroy pathogens, but as these are highly reactive, they also have the capacity to cause DNA damage and alter protein and lipid components of a cell. As a result, cells have evolved a tight regulation of internal redox environment that involves a balanced interplay between free radicals produced and quenched by cellular antioxidants and enzyme systems. Any deregulation of this subtle balance can result in oxidative stress that can lead to various pathological conditions including cancer. Oxidative stress can be a cause of neoplasia, or it can be induced by a growing tumour itself. The link existing between oxidative stress and inflammation is also very strong. Suppressed cellular immune system, especially effector T cell system, is a characteristic of tumour-bearing host. Both the direct oxidative stress caused by tumour cell(s) and oxidative stress mediators present in tumour microenvironment play a significant role in the suppression of effector T cell function and induction of T cell death. This review discusses in detail the complex interplay between tumour-stroma-immune system in the light of oxidative stress that dominates every phase of cancer including initiation, progression and establishment. This review also addresses in detail the mechanisms of oxidative stress-induced T cell dysfunction in tumour-bearing host and also briefly points out the possible therapeutic interventions. PMID- 26286127 TI - Rainfall, runoff and sediment transport in a Mediterranean mountainous catchment. AB - The relation between rainfall, runoff, erosion and sediment transport is highly variable in Mediterranean catchments. Their relation can be modified by land use changes and climate oscillations that, ultimately, will control water and sediment yields. This paper analyses rainfall, runoff and sediment transport relations in a meso-scale Mediterranean mountain catchment, the Ribera Salada (NE Iberian Peninsula). A total of 73 floods recorded between November 2005 and November 2008 at the Inglabaga Sediment Transport Station (114.5 km(2)) have been analysed. Suspended sediment transport and flow discharge were measured continuously. Rainfall data was obtained by means of direct rain gauges and daily rainfall reconstructions from radar information. Results indicate that the annual sediment yield (2.3 t km(-1) y(-1) on average) and the flood-based runoff coefficients (4.1% on average) are low. The Ribera Salada presents a low geomorphological and hydrological activity compared with other Mediterranean mountain catchments. Pearson correlations between rainfall, runoff and sediment transport variables were obtained. The hydrological response of the catchment is controlled by the base flows. The magnitude of suspended sediment concentrations is largely correlated with flood magnitude, while sediment load is correlated with the amount of direct runoff. Multivariate analysis shows that total suspended load can be predicted by integrating rainfall and runoff variables. The total direct runoff is the variable with more weight in the equation. Finally, three main hydro-sedimentary phases within the hydrological year are defined in this catchment: (a) Winter, where the catchment produces only water and very little sediment; (b) Spring, where the majority of water and sediment is produced; and (c) Summer-Autumn, when little runoff is produced but significant amount of sediments is exported out of the catchment. Results show as land use and climate change may have an important role in modifying the cycles of water and sediment yields in Mediterranean mountain catchments. PMID- 26286125 TI - Coagulation factor XII genetic variation, ex vivo thrombin generation, and stroke risk in the elderly: results from the Cardiovascular Health Study. AB - BACKGROUND: The relationships of thrombin generation (TG) with cardiovascular disease risk are underevaluated in population-based cohorts. OBJECTIVES: To evaluate the relationships of TG influenced by the contact and tissue factor coagulation pathways ex vivo with common single-nucleotide polymorphisms (SNPs) and incident cardiovascular disease and stroke. PATIENTS/METHODS: We measured peak TG (pTG) in baseline plasma samples of Cardiovascular Health Study participants (n = 5411), both with and without inhibitory anti-factor XIa antibody (pTG/FXIa(-) ). We evaluated their associations with ~ 50 000 SNPs by using the IBCv2 genotyping array, and with incident cardiovascular disease and stroke events over a median follow-up of 13.2 years. RESULTS: The minor allele for an SNP in the FXII gene (F12), rs1801020, was associated with lower pTG in European-Americans (beta = - 34.2 +/- 3.5 nm; P = 3.3 * 10(-22) ; minor allele frequency [MAF] = 0.23) and African-Americans (beta = - 31.1 +/- 7.9 nm; P = 9.0 * 10(-5) ; MAF = 0.42). Lower FXIa-independent pTG (pTG/FXIa(-) ) was associated with the F12 rs1801020 minor allele, and higher pTG/FXIa(-) was associated with the ABO SNP rs657152 minor allele (beta = 16.3 nm; P = 4.3 * 10(-9) ; MAF = 0.37). The risk factor-adjusted ischemic stroke hazard ratios were 1.09 (95% confidence interval CI 1.01-1.17; P = 0.03) for pTG, 1.06 (95% CI 0.98-1.15; P = 0.17) for pTG/FXIa(-) , and 1.11 (95% CI 1.02-1.21; P = 0.02) for FXIa-dependent pTG (pTG/FXIa(+) ), per one standard deviation increment (n = 834 ischemic strokes). In a multicohort candidate gene analysis, rs1801020 was not associated with incident ischemic stroke (beta = - 0.02; standard error = 0.08; P = 0.81). CONCLUSIONS: These results support the importance of contact activation pathway dependent TG as a risk factor for ischemic stroke, and indicate the importance of F12 SNPs for TG ex vivo and in vivo. PMID- 26286128 TI - Efficacy of a brief manualized intervention Managing Cancer and Living Meaningfully (CALM) adapted to German cancer care settings: study protocol for a randomized controlled trial. AB - BACKGROUND: Although psycho-oncological interventions have been shown to significantly reduce symptoms of anxiety and depression and enhance quality of life, a substantial number of patients with advanced cancer do not receive psycho oncological interventions tailored to their individual situation. Given the lack of reliable data on the efficacy of psycho-oncological interventions in palliative care settings, we aim to examine the efficacy of a brief, manualized individual psychotherapy for patients with advanced cancer: Managing Cancer and Living Meaningfully (CALM). CALM aims to reduce depression and death anxiety, to strengthen communication with health care providers, and to enhance hope and meaning in life. We adapted the intervention for German cancer care settings. METHODS/DESIGN: We use a single-blinded randomized-controlled trial design with two treatment conditions: intervention group (IG, CALM) and control group (CG). Patients in the CG receive a usual non-manualized supportive psycho-oncological intervention (SPI). Patients are randomized between the IG and CG and assessed at baseline (t0), after three (t1) and after 6 months (t2). We include patients with a malignant solid tumor who have tumor stages of III or IV (UICC classification). Patients who are included in the study are at least 18 years old, speak German fluently, score greater than or equal to nine on the PHQ-9 or/and greater than or equal to five on the Distress Thermometer. It is further necessary that there is no evidence of severe cognitive impairments. We measure depression, anxiety, distress, quality of life, demoralization, symptom distress, fatigue as well as spiritual well-being, posttraumatic growth and close relationship experiences using validated questionnaires. We hypothesize that patients in the IG will show a significantly lower level of depression 6 months after baseline compared to patients in the CG. We further hypothesize a significant reduction in anxiety and fatigue as well as significant improvements in psychological and spiritual well being, meaning and post-traumatic growth in the IG compared to CG 6 months after baseline. DISCUSSION: Our study will contribute important statistical evidence on whether CALM can reduce depression and existential distress in a German sample of advanced and highly distressed cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02051660. PMID- 26286130 TI - Preoperative embolization of mediastinal Castleman's disease presenting with stroke. PMID- 26286129 TI - Gender disparities of chronic musculoskeletal disorder burden in the elderly Ghanaian population: study on global ageing and adult health (SAGE WAVE 1). AB - BACKGROUND: Traditionally, non-communicable diseases including musculoskeletal disorders have not been a priority in low-and-middle income countries. The main aim of this paper is to assess age and gender specific burden by estimating the current prevalence of musculoskeletal disorders and associated risk factors in the elderly Ghanaian population. METHODS: Between May 2007 and June 2008, the World Health Organization conducted a nationwide study on AGEing (SAGE) and Adult Health in Ghana. The study employed a multistage cluster sampling strategy to identify participants by stratifying the population by age and setting. A structured questionnaire was used for data collection. A Poisson regression model was fitted with robust error variance. Prevalence estimates took into account the complex survey design and sampling weights. Statistical significance was considered at p <= 0.05 significance level. Statistical analysis was performed with STATA version 11.2. RESULTS: The prevalence rates of chronic back pain and chronic arthritis/joints pain were higher in women than men. The overall crude prevalence's rates were 28.2 and 10.7% for chronic back pain and chronic arthritis/joints pain respectively. Substantial differences existed between men and women in terms of socio-economic status, education level and occupational status. Women with primary education had a chronic back pain prevalence of 36.2% (95% CI; 29.2, 43.3) and chronic arthritis/joints pain prevalence of 15.8% (95% CI; 11.1, 20.6) while their male counterparts had prevalence rates of 29.0% (95% CI; 23.4, 34.5) and 9.8% (95% CI; 6.4, 13.2) respectively. Residence (rural and urban) did not appear to influence the prevalence of chronic back pain and arthritis/joints pain. CONCLUSION: Our findings suggest the existence of sex differences in chronic back pain and chronic arthritis/joint pain in the elderly population in Ghana after adjustment for demographic and socio-economic factors. It indicates the existence of inequalities in health between elderly men and women with women suffering more from chronic back pain and chronic arthritis/joints pain. PMID- 26286131 TI - Successful i-gel insertion combined with Macintosh laryngoscope with a swollen tonsil. PMID- 26286132 TI - Guide wire loss after central venous catheterization: a preventable complication! PMID- 26286133 TI - A simple diagnostic test to confirm correct intravascular placement of peripheral catheters in order to avoid extravasation. AB - BACKGROUND: Intravenous catheters are ubiquitous among modern medical management of patients, yet misplaced or tissued cannulas can result in serious iatrogenic injury due to infiltration or extravasation of injectate. Prevention is difficult, and currently few reliable tests exist to confirm intravascular placement of catheters in awake spontaneously breathing patients. METHODS: Twenty conscious spontaneously breathing healthy volunteers were injected with 50 mL normal saline and 50 mL 4.2%, or 50 mL 2.1%, or 20 mL 4.2% sodium bicarbonate in a random order. A blinded anesthetist observed continuous sampling of exhaled carbon dioxide and was asked to differentiate between the sodium bicarbonate and saline injections. Peak increase in measured exhaled carbon dioxide was also calculated. RESULTS: Exhaled carbon dioxide increased significantly in participants injected with intravenous sodium bicarbonate. Mean peak increase was 7.4 mm Hg (+/-2.1 mm Hg) for 50 mL 4.2% sodium bicarbonate, 4.7 mm Hg (+/-2.5 mm Hg) for 20 mL 4.2% sodium bicarbonate, and 3.5 mm Hg (+/-1. 8 mm Hg) for 50 mL 2.1% sodium bicarbonate. The blinded observer correctly identified the injection as sodium bicarbonate or normal saline in every instance. DISCUSSION: Intravenous injection of dilute sodium bicarbonate with exhaled carbon dioxide monitoring reliably confirms correct intravascular placement of a catheter. A transient increase of exhaled carbon dioxide by 10% or more is an objective and reliable confirmation of intravascular location of the catheter. We recommend using 20 mL of 4.2% sodium bicarbonate to minimize the mEq dose of sodium bicarbonate required. PMID- 26286134 TI - Postdural puncture headache and epidural blood patch use in elderly patients. AB - STUDY OBJECTIVE: Postdural puncture headache is a known complication after lumbar puncture. In elderly patients, postdural puncture headache necessitating epidural blood patch is considered rare. The literature assessing the use and safety of epidural blood patch in the elderly is sparse; therefore, in the present study, the use and efficacy of epidural blood patch in patients 65 years or older was evaluated. DESIGN: Retrospective study. SETTING: Two tertiary and one secondary hospital in Finland. PATIENTS: The Information System Patient Measures Databases were interrogated to identify patients 65 years or older in whom epidural blood patch was performed between 2000 and 2011. INTERVENTIONS AND MEASUREMENTS: The patients' medical records were reviewed for the patient demographics, details of lumbar puncture, postdural puncture headache and other symptoms, conservative treatment, and efficacy and complications of epidural blood patch procedure. MAIN RESULTS: A total of 40 patients had epidural blood patch. Their age varied between 65 and 82 years, and 17 were men. The indications for lumbar puncture were as follows: diagnostic (n = 15), therapeutic (n = 1), spinal anesthesia (n = 15), epidural anesthesia/analgesia (n = 5), and combined spinal-epidural anesthesia (n = 4). Most epidural blood patches were performed between 3 and 5 days (1-20 days) after lumbar puncture. In 34 (85%) patients, epidural blood patch provided a complete and persistent relief of symptoms. In 2 patients, the outcome data were not available, and in 4 patients, symptoms were slightly (n = 3) or not (n = 1) relieved with epidural blood patch. Conservative treatment was then provided. CONCLUSIONS: The elderly may also develop postdural puncture headache, and epidural blood patch is an effective and well-tolerated treatment of persistent and severe symptoms. PMID- 26286135 TI - Comparison of the phlebotomine (Diptera: Psychodidae) fauna of urban, transitional, and wild areas in northern Minas Gerais, Brazil. AB - BACKGROUND: Phlebotomines are directly related to the study of leishmaniases, and so the study of their distribution plays an important role in the epidemiology of these diseases. Collections of phlebotomines were made with the intent of comparing the distribution, richness, diversity, and abundance of species in three distinct environments in an area endemic for tegumentary and visceral leishmaniasis in Minas Gerais State, Brazil. METHODS: Phlebotomines were collected with automatic light traps in urban, transitional, and wild areas from March 2013 to February 2014 in the district of Barra do Guaicui, municipality of Varzea da Palma, Minas Gerais. The distribution patterns of these species of insects, as well as species richness, evenness, and abundance among the different areas, were analyzed. RESULTS: A total of 3,365 phlebotomines belonging to 15 species were collected. The urban area had the greatest abundance whereas the transitional area had the greatest diversity and evenness of species. Nyssomyia intermedia was the most abundant species in the urban area, whereas Evandromyia evandroi was the most abundant in the transitional area and Ev. lenti in the wild area. CONCLUSION: The analysis of our results showed that the distribution of the collected species had distinct profiles between the environments studied. Furthermore our study indicates the potential risk of transmission of leishmaniasis in the urban environment where it was observed had the highest population density and abundance of important vector species of Leishmania. PMID- 26286136 TI - Inducible knockout of Mef2a, -c, and -d from nestin-expressing stem/progenitor cells and their progeny unexpectedly uncouples neurogenesis and dendritogenesis in vivo. AB - Myocyte enhancer factor (Mef)-2 transcription factors are implicated in activity dependent neuronal processes during development, but the role of MEF2 in neural stem/progenitor cells (NSPCs) in the adult brain is unknown. We used a transgenic mouse in which Mef2a, -c, and -d were inducibly deleted in adult nestin expressing NSPCs and their progeny. Recombined cells in the hippocampal granule cell layer were visualized and quantified by yellow fluorescent protein (YFP) expression. In control mice, postmitotic neurons expressed Mef2a, -c, and -d, whereas type 1 stem cells and proliferating progenitors did not. Based on this expression, we hypothesized that Mef2a, -c, and -d deletion in adult nestin expressing NSPCs and their progeny would result in fewer mature neurons. Control mice revealed an increase in YFP(+) neurons and dendrite formation over time. Contrary to our hypothesis, inducible Mef2 KO mice also displayed an increase in YFP(+) neurons over time-but with significantly stunted dendrites-suggesting an uncoupling of neuron survival and dendritogenesis. We also found non-cell autonomous effects after Mef2a, -c, and -d deletion. These in vivo findings indicate a surprising functional role for Mef2a, -c, and -d in cell- and non-cell autonomous control of adult hippocampal neurogenesis that is distinct from its role during development. PMID- 26286137 TI - Yoga's effect on inflammatory biomarkers and metabolic risk factors in a high risk population - a controlled trial in primary care. AB - BACKGROUND: Yoga can reduce blood pressure and has also been suggested to reduce inflammatory biomarkers and metabolic risk factors for cardiovascular diseases (CVDs). We aimed to assess the benefit of two yoga interventions on inflammatory biomarkers and metabolic risk factors in a high risk population in primary care. METHODS: Adult patients from a health care center in Sweden, with diagnosed hypertension, were invited to undergo a baseline check at the health care center. Baseline check included standardized blood pressure measurement, BMI and weight circumference measurements, blood sampling (hs-CRP, IL-6, FP-glucose, HbA1c, cholesterol, TG, LDL and HDL) and a questionnaire on self-rated quality of life (WHOQOL-BREF). There were three groups: 1) yoga class with yoga instructor; 2) yoga at home; and 3) a control group. In total, 83 patients were included and matched at the group level for systolic blood pressure. A majority of the patients (92 %) were on antihypertensive medication, which they were requested not to change during the study. After 12 weeks of intervention, the assessments were performed again. RESULTS: We recorded no evidence that yoga altered inflammatory biomarkers or metabolic risk factors in our study population. A total of 49 participants (59 %) met the criteria for metabolic syndrome. CONCLUSION: The yoga interventions performed in our study did not affect inflammatory biomarkers or metabolic risk factors associated with CVD in the study population of primary care patients with hypertension. Further randomized trials are needed to elucidate the effects of yoga on CVD risk factors in this particular group. TRAIL REGISTRATION: NCT01302535 , February 22, 2011. PMID- 26286138 TI - Programmed regulation of rat offspring adipogenic transcription factor (PPARgamma) by maternal nutrition. AB - We determined the protein expression of adipogenic transcription factor, peroxisome proliferator-activated receptor gamma (PPARgamma) and its co-repressor and co-activator complexes in adipose tissue from the obese offspring of under- and over-nourished dams. Female rats were fed either a high-fat (60% kcal) or control (10% kcal) diet before mating, and throughout pregnancy and lactation (Mat-OB). Additional dams were 50% food-restricted from pregnancy day 10 to term [intrauterine growth-restricted (IUGR)]. Adipose tissue protein expression was analyzed in newborn and adult male offspring. Normal birth weight Mat-OB and low birth weight IUGR newborns had upregulated PPARgamma with variable changes in co repressors and co-activators. As obese adults, Mat-OB and IUGR offspring had increased PPARgamma with decreased co-repressor and increased co-activator expression. Nutritionally programmed increased PPARgamma expression is associated with altered expression of its co-regulators in the newborn and adult offspring. Functional studies of PPARgamma co-regulators are necessary to establish their role in PPARgamma-mediated programmed obesity. PMID- 26286139 TI - Use of the Blue Button Online Tool for Sharing Health Information: Qualitative Interviews With Patients and Providers. AB - BACKGROUND: Information sharing between providers is critical for care coordination, especially in health systems such as the United States Department of Veterans Affairs (VA), where many patients also receive care from other health care organizations. Patients can facilitate this sharing by using the Blue Button, an online tool that promotes patients' ability to view, print, and download their health records. OBJECTIVE: The aim of this study was to characterize (1) patients' use of Blue Button, an online information-sharing tool in VA's patient portal, My HealtheVet, (2) information-sharing practices between VA and non-VA providers, and (3) how providers and patients use a printed Blue Button report during a clinical visit. METHODS: Semistructured qualitative interviews were conducted with 34 VA patients, 10 VA providers, and 9 non-VA providers. Interviews focused on patients' use of Blue Button, information sharing practices between VA and non-VA providers, and how patients and providers use a printed Blue Button report during a clinical visit. Qualitative themes were identified through iterative rounds of coding starting with an a priori schema based on technology adoption theory. RESULTS: Information sharing between VA and non-VA providers relied primarily on the patient. Patients most commonly used Blue Button to access and share VA laboratory results. Providers recognized the need for improved information sharing, valued the Blue Button printout, and expressed interest in a way to share information electronically across settings. CONCLUSIONS: Consumer-oriented technologies such as Blue Button can facilitate patients sharing health information with providers in other health care systems; however, more education is needed to inform patients of this use to facilitate care coordination. Additional research is needed to explore how personal health record documents, such as Blue Button reports, can be easily shared and incorporated into the clinical workflow of providers. PMID- 26286142 TI - PREVALENCE OF CHILD MARRIAGE AMONG BANGLADESHI WOMEN AND TREND OF CHANGE OVER TIME. AB - Many Bangladeshi women marry early, and many marry before the legal age of 18 years. This practice has been associated with a higher risk of health and medical morbidities, and also early pregnancy with higher pre- and postnatal complications. The aim of this study was to determine the prevalence, and factors associated with, child marriage among Bangladeshi women using multiple binary logistic regression analysis of data from the BDHS-2011. Further analysis on the trend of age at first marriage was performed with additional data sets from previous surveys. The mean and median of ages at first marriage of Bangladeshi women in 2011 were 15.69+/-2.97 and 15.00 years, respectively. A remarkably high percentage (78.2%) married before the age of 18; of these, 5.5% married at a very early age (before 13 years of age). Binary logistic regression analysis demonstrated that uneducated women were more likely to be married early (p<0.001) than those with secondary and higher education. Child marriage was especially pronounced among women with uneducated husbands, Muslims, those with poor economic backgrounds and those living in rural areas. Further analysis including data from previous BDHS surveys showed that child marriage among Bangladeshi women had a decreasing trend from 1993-94 to 2011. These results show that child marriage was very common in Bangladesh, and closely associated with low level of education and low economic status. The decreasing trend in child marriage indicates an improvement over the past two decades but more effort is needed to further reduce and eventually eliminate the practice. PMID- 26286141 TI - Umeclidinium/vilanterol versus fluticasone propionate/salmeterol in COPD: a randomised trial. AB - BACKGROUND: Umeclidinium (UMEC; long-acting muscarinic antagonist) plus vilanterol (VI; long-acting beta2 agonist [LABA]) and the LABA/inhaled corticosteroid fluticasone propionate/salmeterol (FP/SAL) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD). This 12 week, multicentre, double-blind, parallel-group, double-dummy study compared the efficacy and safety of these treatments in symptomatic patients with moderate-to severe COPD with no exacerbations in the year prior to enrolment. METHODS: Patients (n = 717) were randomised 1:1 to once-daily UMEC/VI 62.5/25 mcg or twice daily FP/SAL 500/50 mcg. Endpoints included 0-24 h weighted mean (wm) forced expiratory volume in 1 s (FEV1) (Day 84; primary), trough FEV1 (Day 85; secondary), other lung function endpoints, symptoms, quality of life (QoL) and safety. RESULTS: Improvements with UMEC/VI versus FP/SAL were 0.080 L (95 % confidence interval: 0.046-0.113; wmFEV1) and 0.090 L (0.055-0.125; trough FEV1) (both p < 0.001). UMEC/VI statistically significantly improved all other lung function measures versus FP/SAL. Both treatments demonstrated a clinically meaningful improvement in symptoms (Transition Dyspnoea Index >=1 unit) and QoL (St George's Respiratory Questionnaire Total score >=4 unit decrease from baseline) over 12 weeks. The incidence of adverse events was 28 % (UMEC/VI) and 29 % (FP/SAL); nasopharyngitis and headache were most common. CONCLUSIONS: Once daily UMEC/VI 62.5/25 mcg over 12 weeks resulted in significant and sustained improvements in lung function versus twice-daily FP/SAL 500/50 mcg in patients with moderate-to-severe COPD and with no exacerbations in the year prior to enrolment. TRIAL REGISTRATION: NCT01822899 Registration date: March 28, 2013. PMID- 26286140 TI - Na,K-ATPase beta1-subunit is a target of sonic hedgehog signaling and enhances medulloblastoma tumorigenicity. AB - BACKGROUND: The Sonic hedgehog (Shh) signaling pathway plays an important role in cerebellar development, and mutations leading to hyperactive Shh signaling have been associated with certain forms of medulloblastoma, a common form of pediatric brain cancer. While the fundamentals of this pathway are known, the molecular targets contributing to Shh-mediated proliferation and transformation are still poorly understood. Na,K-ATPase is a ubiquitous enzyme that maintains intracellular ion homeostasis and functions as a signaling scaffold and a cell adhesion molecule. Changes in Na,K-ATPase function and subunit expression have been reported in several cancers and loss of the beta1-subunit has been associated with a poorly differentiated phenotype in carcinoma but its role in medulloblastoma progression is not known. METHODS: Human medulloblastoma cell lines and primary cultures of cerebellar granule cell precursors (CGP) were used to determine whether Shh regulates Na,K-ATPase expression. Smo/Smo medulloblastoma were used to assess the Na,K-ATPase levels in vivo. Na,K-ATPase beta1-subunit was knocked down in DAOY cells to test its role in medulloblastoma cell proliferation and tumorigenicity. RESULTS: Na,K-ATPase beta1-subunit levels increased with differentiation in normal CGP cells. Activation of Shh signaling resulted in reduced beta1-subunit mRNA and protein levels and was mimicked by overexpression of Gli1and Bmi1, both members of the Shh signaling cascade; overexpression of Bmi1 reduced beta1-subunit promoter activity. In human medulloblastoma cells, low beta1-subunit levels were associated with increased cell proliferation and in vivo tumorigenesis. CONCLUSIONS: Na,K-ATPase beta1 subunit is a target of the Shh signaling pathway and loss of beta1-subunit expression may contribute to tumor development and progression not only in carcinoma but also in medulloblastoma, a tumor of neuronal origin. PMID- 26286143 TI - An avian influenza A (H7N9) virus vaccine candidate based on the fusion protein of hemagglutinin globular head and Salmonella typhimurium flagellin. AB - BACKGROUND: A novel influenza virus, subtype H7N9, circulated through China in 2013-2014. Its higher rates of human infection in a wide range of locations within China and the associated increased likelihood of human-to-human transmission have caused global concern. Recombinant subunit vaccines provide safe and targeted protection against viral infections. However, the protective efficacy of recombinant subunit vaccines tends to be less potent than vaccines made from whole viruses. Studies have shown that bacterial flagellin has strong adjuvant activity and induces protective immune responses. RESULTS: In this study, we used overlap-PCR to generate an H7N9 influenza recombinant subunit vaccine that fused the globular head domain (HA1-2, aa 62-284) of the protective hemagglutinin (HA) antigen with the potent TLR5 ligand, Salmonella typhimurium flagellin (fliC). The resulting fusion protein, HA1-2-fliC, was efficiently expressed in an Escherichia coli prokaryotic expression system, and Western blotting and TLR5-stimulating activity analysis confirmed that the HA1-2-fliC moiety could be faithfully refolded to take on the native HA and fliC conformations. In a C3H/HeJ mouse model of intraperitoneal vaccination, the fusion protein elicited significant and robust HA1-2-specific serum IgG titers, maintaining high levels for at least 3 months in the vaccinated animals, and induced similar levels of HA1-2-specific IgG1 and IgG2a that were detectable 12 days after the third immunization. HA1-2-fliC was also found to be capable of triggering the production of neutralizing antibodies, as assessed by measuring hemagglutination inhibition titers. CONCLUSIONS: We conclude that immunization with HA1-2-fliC induces potent HA1-2-specific responses, offering significant promise for the development of a successful recombinant subunit vaccine for avian influenza A (H7N9). PMID- 26286144 TI - Total knee arthroplasty in a patient with a fused ipsilateral hip. AB - BACKGROUND: Many patients undergoing total knee replacement for joint degeneration may have cartilage wear in other joints and thus may already have had various other surgical procedures performed for these. To date, there is no data or description in the medical literature detailing how to perform a total knee replacement in a patient who previously underwent an ipsilateral hip fusion. METHOD: We describe how this is done in a patient who had her ipsilateral hip fused in 30 degrees of flexion. This presents a surgical challenge because the knee can only be flexed to 70 degrees if done in the conventional supine position. This not only makes exposure more difficult but can also lead to complications including component malpositioning and extensor mechanism problems, such as patellar tendon rupture. We present this case study and describe, with the aid of a series of intra-operative photographs, how this can be performed, with special focus on patient positioning to optimize knee exposure in a patient with a previous hip fusion. RESULTS: The modifications made during surgery allowed the knee replacement to be carried out uneventfully. The patient recovered well and was able to return to her usual activities. CONCLUSION: We had to make various modifications to the intra-operative positioning in order to carry out the surgery. We hope these practical pointers will help clinicians faced with a similar situation in the future. PMID- 26286145 TI - Immune phenotypes of microglia in human neurodegenerative disease: challenges to detecting microglial polarization in human brains. AB - Inflammatory responses in the brain, which can be demonstrated by changes in properties of microglia, the brain-resident macrophages, are a common feature of human neurodegenerative diseases. Different monocyte/macrophage phenotypes have been defined by changes in expression of cytokines, receptors and other markers as a response to different classes of stimuli. Monocytes, macrophages and microglia can have a range of phenotypes with associated properties depending on their microenvironment. Macrophage/microglia polarization states have been defined as classical activation (M1), alternative activation (M2a), type II alternative activation (M2b) or acquired deactivation (M2c). Available markers for identifying microglial phenotypes in human brains are still limited; those available provide incomplete information on the functions or polarization states of microglia observed in tissues from diseases such as Alzheimer's disease, Parkinson's disease and multiple sclerosis. The most widely used marker to describe activated microglia in human brains, particularly diseased brains, has been HLA-DR, the major histocompatibility complex II protein. HLA-DR-positive microglia can have a wide range of activation morphologies that are affected not only by disease pathology, but also by their differentiation states and brain regions. Two other widely used markers to identify microglia in human brains are ionized calcium binding adaptor molecule-1 and CD68. Although their expression changes in diseased brains, these markers do not show specificity for different phenotypes. Over the years there have been studies with additional markers that attempt to further define microglial properties, particularly in Alzheimer's disease brains. Most studies have employed immunohistochemical techniques to identify microglia in tissue sections, but recent advances in this field have allowed gene expression profiling of microglia upon immediate isolation from brains. We will review which markers might better define different activation phenotypes of microglia in human brains and whether they fit into current microglial polarization schemes. PMID- 26286146 TI - Improving child survival through a district management strengthening and community empowerment intervention: early implementation experiences from Uganda. AB - BACKGROUND: The Community and District Empowerment for Scale-up (CODES) project pioneered the implementation of a comprehensive district management and community empowerment intervention in five districts in Uganda. In order to improve effective coverage and quality of child survival interventions CODES combines UNICEF tools designed to systematize priority setting, allocation of resources and problem solving with Community dialogues based on Citizen Report Cards and U Reports used to engage and empower communities in monitoring health service provision and to demand for quality services. This paper presents early implementation experiences in five pilot districts and lessons learnt during the first 2 years of implementation. METHODS: This qualitative study was comprised of 38 in-depth interviews with members of the District Health Teams (DHTs) and two implementing partners. These were supplemented by observations during implementation and documents review. Thematic analysis was used to distill early implementation experiences and lessons learnt from the process. RESULTS: All five districts health teams with support from the implementing partners were able to adopt the UNICEF tools and to develop district health operational work plans that were evidence-based. Members of the DHTs described the approach introduced by the CODES project as a more systematic planning process and very much appreciated it. Districts were also able to implement some of the priority activities included in their work plans but limited financial resources and fiscal decision space constrained the implementation of some activities that were prioritized. Community dialogues based on Citizen Report Cards (CRC) increased community awareness of available health care services, their utilization and led to discussions on service delivery, barriers to service utilization and processes for improvement. Community dialogues were also instrumental in bringing together service users, providers and leaders to discuss problems and find solutions. The dialogues however are more likely to be sustainable if embedded in existing community structures and conducted by district based facilitators. U report as a community feedback mechanism registered a low response rate. CONCLUSION: The UNICEF tools were adopted at district level and generally well perceived by the DHTs. The limited resources and fiscal decision space however can hinder implementation of prioritized activities. Community dialogues based on CRCs can bring service providers and the community together but need to be embedded in existing community structures for sustainability. PMID- 26286147 TI - Efficacy and safety of Qing-Feng-Gan-Ke Granules in patients with postinfectious cough: study protocol of a novel-design phase III placebo-controlled, double blind randomized trial. AB - BACKGROUND: Postinfectious cough (PIC) is a common condition that affects millions of people worldwide every year. There is Western medicine for this condition but the treatment effect is often incomplete. Traditional Chinese medicine (TCM) has been increasingly prescribed for patients with PIC. Preliminary trials on Qing-Feng-Gan-Ke-Granules (QFGKG) conveyed promising results in treating PIC. This protocol describes an ongoing phase III randomized controlled clinical trial, designed according to a novel methodology of "one study, one primary outcome", with the objective of evaluating the efficacy and safety of QFGKG in patients suffering from PIC. METHODS/DESIGN: This is a multicenter, phase III, randomized, double-blind, parallel-group, placebo controlled clinical trial, comprising two simultaneously conducted study parts, part A and part B, intending to investigate two primary outcomes, i.e. time to cough resolution and cough symptom score, respectively. A total of 480 patients, aged 18 to 65 years, who complain of an ongoing persistent cough that has been lasting >= 3 weeks, will be recruited from six participating sites and then randomized to receive QFGKG 12.0 g twice daily or placebo 12.0 g twice daily. Each part will enroll 240 patients, with 180 patients being allocated to the QFGKG group and 60 to the placebo group. DISCUSSION: Although traditional Chinese medicine is a structured intervention that has shown some promise in treating persistent cough, existing unconvincing evidence has noted limitations. This is a rare well-designed and rigorously-controlled, randomized, double-blind trial to evaluate the effects and safety of a Chinese herbal medicine in patients with postinfectious cough, providing tangible benefits for clinical research. Results of this trial are inclined to be conjectured as more truthful by implementing separate study parts that specifically estimate exclusive primary outcome. It will not only provide robust clinical evidence on the efficacy and safety of QFGKG for postinfectious cough, but will also provide a critical piece of information on the availability and superiority of a novel methodology for future clinical trials. The current trial is ongoing with recruitment of the predetermined number of patients being in progress. TRIAL REGISTRATION: The two parts of this trial were separately registered with the Chinese Clinical Trial Registry: ChiCTR-TRC-13003278 (part A); and ChiCTR-TRC-13003337 (part B). PMID- 26286150 TI - Role of Small Pd Ensembles in Boosting CO Oxidation in AuPd Alloys. AB - We present a theoretical explanation on how PdAu alloy catalysts can enhance the oxidation of CO molecules based on density functional theory calculations of CO adsorption and oxidation on AuPd/Pd(111) surfaces. Our study suggests that the enhanced activity is largely attributed to the possible existence of "partially poisoned" Pd ensembles that accommodate fewer CO molecules than Pd atoms. Whereas the oxidation of preadsorbed CO is likely governed by O2 trapping, our study shows that small Pd ensembles such as dimers and compact trimers tend to provide more active sites than larger ensembles; CO adsorbed on a Pd monomer is found to react hardly with O2 to form CO2. In addition, we find the tendency of CO-induced Pd agglomeration, which may in turn facilitate CO oxidation by creating more dimers and compact trimers as compared with the adsorbate-free surface where monomers are likely prevailing. PMID- 26286149 TI - Rapid Virological Response Represents the Highest Prediction Factor of Response to Antiviral Treatment in HCV-Related Chronic Hepatitis: a Multicenter Retrospective Study. AB - BACKGROUND: Standard [i.e. pegylated interferon (Peg-IFN) + ribavirin] treatment of hepatitis C virus (HCV)-related chronic hepatitis is associated with a sustained virological response (SVR) in 50 - 90% of patients. A rapid virological response (RVR) (i.e. negative HCV-RNA after 4 weeks of treatment) predicts SVR in almost 90% of patients. OBJECTIVES: The main aim of this study was to assess the strength of RVR, as a predictive factor of antiviral treatment response. PATIENTS AND METHODS: Using univariate and multivariate analysis, we retrospectively evaluated biochemical, metabolic, genetic and viral variables that might affect both RVR and SVR to Peg-IFN plus ribavirin, in 315 consecutive outpatients affected by HCV-related chronic hepatitis. RESULTS: At univariate analysis, staging, body mass index, RVR, genotype and viral load were significantly related to SVR (P < 0.001). At multivariate analysis, RVR and genotype remained significant (P < 0.00001). The RVR had a predictive value of 83%. At univariate and multivariate analyses, diabetes (P = 0.003), genotype 2 (P = 0.000) and HCV RNA values (P = 0.016) were independent predictors of RVR, even though at multivariate analyses, only genotype 2 was significantly related to RVR. When we stratified patients, according to genotype, no laboratory or clinical factors were predictive of RVR in genotype 1 patients at either univariate or multivariate analysis. In genotype 2 patients, staging (P = 0.029) and diabetes (P = 0.001) were the only significant predictors of RVR at univariate analyses, whereas no factor was independently related to RVR, at multivariate analysis. CONCLUSIONS: The RVR is the strongest factor of SVR and infection with HCV genotype 2 is significantly associated with RVR. Neither biochemical and/or metabolic factors seem to exert influence on RVR. PMID- 26286148 TI - Neural-Network Scoring Functions Identify Structurally Novel Estrogen-Receptor Ligands. AB - The magnitude of the investment required to bring a drug to the market hinders medical progress, requiring hundreds of millions of dollars and years of research and development. Any innovation that improves the efficiency of the drug discovery process has the potential to accelerate the delivery of new treatments to countless patients in need. "Virtual screening," wherein molecules are first tested in silico in order to prioritize compounds for subsequent experimental testing, is one such innovation. Although the traditional scoring functions used in virtual screens have proven useful, improved accuracy requires novel approaches. In the current work, we use the estrogen receptor to demonstrate that neural networks are adept at identifying structurally novel small molecules that bind to a selected drug target, ultimately allowing experimentalists to test fewer compounds in the earliest stages of lead identification while obtaining higher hit rates. We describe 39 novel estrogen-receptor ligands identified in silico with experimentally determined Ki values ranging from 460 nM to 20 MUM, presented here for the first time. PMID- 26286151 TI - Controlling Glycosyl Bond Conformation of Guanine Nucleosides: Stabilization of the anti Conformer in 5'-O-Ethylguanosine. AB - Nucleosides that consist of base and sugar moieties can adopt two main conformations, syn and anti, about the glycosidic bond. We have investigated the conformational properties of guanine nucleosides in the gas phase by using laser desorption combined with IR-UV double resonance spectroscopy. In guanosine, syn conformation is preferred as a result of internal hydrogen bonding between the 5' OH group of the sugar and the N3 site of the guanine moiety. We have therefore employed a chemically modified nucleoside 5'-O-ethylguanosine, in which possible glycosyl bond conformations are restricted upon ethylation of the 5'-OH group. The result shows that anti conformer is stabilized by the formation of hydrogen bonding involving the 2'-OH group. PMID- 26286152 TI - Does a Molecule-Specific Density Functional Give an Accurate Electron Density? The Challenging Case of the CuCl Electric Field Gradient. AB - In the framework of determining system-specific long-range corrected density functionals, the question is addressed whether such functionals, tuned to satisfy the condition -epsilon(HOMO) = IP or other energetic criteria, provide accurate electron densities. A nonempirical physically motivated two-dimensional tuning of range-separated hybrid functionals is proposed and applied to the particularly challenging case of a molecular property that depends directly on the ground state density: the copper electric field gradient (EFG) in CuCl. From a continuous range of functional parametrizations that closely satisfy epsilon(HOMO) = IP and the correct asymptotic behavior of the potential, the one that best fulfills the straight-line behavior of E(N), the energy as a function of a fractional electron number N, was found to provide the most accurate electron density as evidenced by calculated EFGs. The functional also performs well for related Cu systems. PMID- 26286153 TI - Toward Low-Temperature Dehydrogenation Catalysis: Isophorone Adsorbed on Pd(111). AB - Adsorbate geometry and reaction dynamics play essential roles in catalytic processes at surfaces. Here we present a theoretical and experimental study for a model functional organic/metal interface: isophorone (C9H14O) adsorbed on the Pd(111) surface. Density functional theory calculations with the Perdew-Burke Ernzerhoff (PBE) functional including van der Waals (vdW) interactions, in combination with infrared spectroscopy and temperature-programmed desorption (TPD) experiments, reveal the reaction pathway between the weakly chemisorbed reactant (C9H14O) and the strongly chemisorbed product (C9H10O), which occurs by the cleavage of four C-H bonds below 250 K. Analysis of the TPD spectrum is consistent with the relatively small magnitude of the activation barrier derived from PBE+vdW calculations, demonstrating the feasibility of low-temperature dehydrogenation. PMID- 26286154 TI - Hierarchal Light-Harvesting Aggregates and Their Potential for Solar Energy Applications. AB - The tunable optical properties of self-assembled chromophores are exploited by photosynthetic organisms to optimize their ability to harvest a broad range of the solar spectrum. Similarly, the efficiency of solar photovoltaic and photoelectrochemical devices depends strongly on the coincidence of the absorption spectrum of the photoactive components with the spectrum of the sun. While the possibility of borrowing ideas about light-harvesting aggregates from nature in order to improve the efficiency of solar energy conversion is quite attractive, progress to date is hindered by incomplete understanding of aggregate internal structure and its relation to excitonic states. In this Perspective, we describe our recent work on the hierarchal structure of self-assembled porphyrin aggregates that are similar to light-harvesting complexes of photosynthetic bacteria. We address the question of whether aggregation can be beneficial to dye sensitized solar energy conversion and present promising results for a solar cell based on an abundant plant pigment that displays signatures of aggregation when adsorbed on TiO2. PMID- 26286155 TI - Simultaneous Ionization-Detected Stimulated Raman and Visible-Visible-Ultraviolet Hole-Burning Spectra of Two Tryptamine Conformers. AB - A key first step toward probing structures and interactions of individual conformers of isolated flexible molecules is uncovering their characteristic spectral signatures. Here, conformation-specific ionization-detected stimulated Raman (IDSR) and visible-visible-ultraviolet hole-burning spectra were measured simultaneously to determine the unique signatures of the two most stable conformers of tryptamine in the gas phase. These signatures together with the comparison of the IDSR spectra to the computationally predicted Raman spectra assisted in their characterization and structural identification. This new approach offers high selectivity and is foreseen to be an improved diagnostic tool for dissection of conformers of flexible molecules. PMID- 26286156 TI - Nano Pinstripes: TiO2 Nanostripe Formation by Nanoparticle-Mediated Pinning of Step Edges. AB - The present scanning tunneling microscopy study describes the high-temperature growth of TiO2 nanostripes with tunable width, orientation, and spacing, mediated by thermally stable micellar Pt and Au NPs deposited on TiO2(110). This phenomenon could not be explained by spillover effects but is based on the preferential stabilization of [110] step edges on TiO2(110) by the metal NPs. Contrary to the behavior of physical-vapor-deposited NPs, which are known to move toward step edges upon annealing, our micellar NPs remain immobile up to 1000 degrees C. Instead, the mobility of TiO2 step edges toward the micellar NPs, where they become stabilized, is observed. Our findings are relevant to the technological application of nanostructured materials in the fields of catalysis, molecular electronics, and plasmonics. PMID- 26286157 TI - Acoustic Vibrations in Bimetallic Au@Pd Core-Shell Nanorods. AB - The acoustic vibrations of gold nanorods coated with palladium were investigated as a function of Pd amount using ultrafast pump-probe spectroscopy. Both the extensional and breathing vibrational modes of the nanorods were coherently excited and detected. This permits precise determination of their periods, which were found to decrease and increase with Pd deposition, for the extensional and vibrational modes, respectively. These opposite behaviors reflect changes of the nanoparticle size and mechanical properties, in agreement with numerical simulations. Comparison of experimental and computed periods yields information on the amount of deposited Pd, providing a novel tool to characterize bicomponent nano-objects for small fractions of one of the components (Pd/Au atomic fraction down to 5%). PMID- 26286158 TI - Mesocrystals - Properties and Applications. AB - Mesocrystals are a new class of nanostructured solid materials, which are most often made of crystallographically oriented nanoparticles. Structural features, properties, and possible applications of mesocrystals are summarized in this paper. Due to their unique structural features and the resulting physical and physicochemical properties, mesocrystals are expected to play a significant role in improving the performance of materials in many applications. These are as diverse as heterogeneous photocatalysts, electrodes, optoelectronics, biomedical materials, hard templates, and lightweight structural materials. PMID- 26286159 TI - Progress in Heterogeneous Photocatalysis: From Classical Radical Chemistry to Engineering Nanomaterials and Solar Reactors. AB - The field of heterogeneous photocatalysis has expanded rapidly in the last four decades, having undergone various evolutionary phases related to energy and the environment. The two most significant applications of photocatalysis are geared toward solar water splitting and the purification of air and water. Notably, the interdisciplinary nature of the field has increased significantly, incorporating semiconductor physics, surface sciences, photo and physical chemistry, materials science, and chemical engineering. Whereas this forms the basis on which the field continues to grow, adequate bridging of multidisciplinary knowledge remains essential. By recalling some of the classical fundamentals of photocatalysis, this Perspective provides contemporary views on heterogeneous photochemical conversion, encompassing charge transport characteristics, radical chemistry and organic degradation mechanisms, photocatalyst design, and photoreactor engineering. PMID- 26286160 TI - On the Field Dependence of Free Charge Carrier Generation and Recombination in Blends of PCPDTBT/PC70BM: Influence of Solvent Additives. AB - We have applied time-delayed collection field (TDCF) and charge extraction by linearly increasing voltage (CELIV) to investigate the photogeneration, transport, and recombination of charge carriers in blends composed of PCPDTBT/PC70BM processed with and without the solvent additive diiodooctane. The results suggest that the solvent additive has severe impacts on the elementary processes involved in the photon to collected electron conversion in these blends. First, a pronounced field dependence of the free carrier generation is found for both blends, where the field dependence is stronger without the additive. Second, the fate of charge carriers in both blends can be described with a rather high bimolecular recombination coefficients, which increase with decreasing internal field. Third, the mobility is three to four times higher with the additive. Both blends show a negative field dependence of mobility, which we suggest to cause bias-dependent recombination coefficients. PMID- 26286161 TI - In situ Electrochemical Small-Angle Neutron Scattering (eSANS) for Quantitative Structure and Redox Properties of Nanoparticles. AB - The rapid growth in nanomaterial applications have revealed limitations in available physicochemical characterization methods. An in situ electrochemical small-angle neutron scattering (eSANS) methodology was devised that enables direct measurements of nanomaterial dispersion structure while undergoing reduction-oxidation (redox) reactions at the vitreous carbon electrode. Furthermore, these porous electrodes are amenable to contrast-variant neutron scattering strategies to measure nanoparticle structure and polymer conformation in multicomponent systems. The eSANS method was tested for feasibility by characterizing ZnO nanoparticles in 50 mmol/L NaCl deuterium oxide solution undergoing bulk electrolysis at negative potentials. Irreversible nanoparticle structural changes are observed during the potential cycle. The complete reduction of Zn(2+) to Zn(0) nanoparticles is unlikely, but a peak in the characteristic correlation length occurs during the redox bias with reduced average characteristic size. PMID- 26286162 TI - Surface-Enhanced Raman Scattering on Hierarchical Porous Cuprous Oxide Nanostructures in Nanoshell and Thin-Film Geometries. AB - Understanding the mechanism of surface-enhanced Raman scattering (SERS) of molecules on semiconductor nanostructures is directly related to our capabilities of designing and optimizing new SERS-active substrates for broad applications in the field of molecular detection and characterization. Here, we present an exploration of using cuprous oxide nanostructures with hierarchical porosity for enhancing Raman signals of adsorbed probe molecules. Distinct SERS signals were detected on both individual polycrystalline nanoshells and porous thin films composed of cuprous oxide nanocrystals. The observed enhancement of SERS signals can be interpreted as synergistic effects of strong chemical interactions between the probe molecules and cuprous oxide surfaces, localized electromagnetic field enhancement, and the unique hierarchical porosity of the nanostructures. Our work introduced a novel type of semiconductor substrates for high-performance SERS and extended the applications of cuprous oxide nanostructures to spectroscopy-based molecular sensing and characterizations. PMID- 26286163 TI - Manipulation of Charge Transfer Across Semiconductor Interface. A Criterion That Cannot Be Ignored in Photocatalyst Design. AB - The Perspective focuses on photoinduced electron transfer between semiconductor metal and semiconductor-semiconductor nanostructures and factors that influence the rate of electron transfer at the interface. The storage and discharge properties of metal nanoparticles play an important role in dictating the photocatalytic performance of semiconductor-metal composite assemblies. Both electron and hole transfer across the interface with comparable rates are important in maintaining high photocatalytic efficiency and stability of the semiconductor assemblies. Coupled semiconductors of well-matched band energies are convenient to improve charge separation. Furthermore, semiconductor and metal nanoparticles assembled on reduced graphene oxide sheets offer new ways to design multifunctional catalyst mat. The fundamental understanding of charge-transfer processes is important in the future design of light-harvesting assemblies. PMID- 26286164 TI - Semiconductor Photocatalysis - Past, Present, and Future Outlook. PMID- 26286165 TI - Nanodroplet Depinning from Nanoparticles. AB - Nanoscale defects on a substrate affect the sliding motion of water droplets. Using in situ transmission electron microscopy imaging, we visualized the depinning dynamics of water nanodroplets from gold nanoparticles on a flat SiNx surface. Our observations showed that nanoscale pinning effects of the gold nanoparticle oppose the lateral forces, resulting in stretching, even breakup, of the water nanodroplet. Using continuum long wave theory, we modeled the dynamics of a nanodroplet depinning from a nanoparticle of comparable length scales, and the model results are consistent with experimental findings and show formation of a capillary bridge prior to nanodroplet depinning. Our findings have important implications on surface cleaning at the nanoscale. PMID- 26286166 TI - Stimuli-responsive chromism in organophosphorus chemistry. AB - Changes in color are one of the most obvious and easily followed responses that can be induced by an external stimulus. pi-Conjugated organophosphorus compounds are on the rise to challenge established systems by opening up new and simple pathways to diversely modified optoelectronic properties--the main challenge for the development of new chromic materials. Relevant stimuli highlighted in this Frontier article include electronic current (electrochromism), light (photochromism), solvent polarity (solvatochromism), aggregation formation (aggregation induced emission, AIE), mechanical force (mechanochromism), temperature (thermochromism), organic solvent vapor (vapochromism), and pH (halochromism). PMID- 26286167 TI - Electrochemistry in (Bio)-Nanoanalysis, Electromigration and Liquid Phase Separations. PMID- 26286172 TI - Insulin growth factor-1 (IGF-1) enhances hippocampal excitatory and seizure activity through IGF-1 receptor-mediated mechanisms in the epileptic brain. AB - Insulin-like growth factor-1 (IGF-1) is known to promote neurogenesis and survival. However, recent studies have suggested that IGF-1 regulates neuronal firing and excitatory neurotransmission. In the present study, focusing on temporal lobe epilepsy, we found that IGF-1 levels and IGF-1 receptor activation are increased in human epileptogenic tissues, and pilocarpine- and pentylenetetrazole-treated rat models. Using an acute model of seizures, we showed that lateral cerebroventricular infusion of IGF-1 elevates IGF-1 receptor (IGF-1R) signalling before pilocarpine application had proconvulsant effects. In vivo electroencephalogram recordings and power spectrogram analysis of local field potential revealed that IGF-1 promotes epileptiform activities. This effect is diminished by co-application of an IGF-1R inhibitor. In an in vitro electrophysiological study, we demonstrated that IGF-1 enhancement of excitatory neurotransmission and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor- and N-methyl-D-aspartate receptor-mediated currents is inhibited by IGF 1R inhibitor. Finally, activation of extracellular signal-related kinase (ERK) 1/2 and protein kinase B (Akt) in seizures in rats is increased by exogenous IGF 1 and diminished by picropodophyllin. A behavioural study reveals that the ERK1/2 or Akt inhibitor attenuates seizure activity. These results indicate that increased IGF-1 levels after recurrent hippocampal neuronal firings might, in turn, promote seizure activity via IGF-1R-dependent mechanisms. The present study presents a previously unappreciated role of IGF-1R in the development of seizure activity. PMID- 26286173 TI - Platinum(II) Monomer and Dimer Complexes with a Bis(oxazolinyl)phenyl Pincer Ligand. AB - A series of platinum(II) complexes with the formulas Pt(phebox)(L)(+) (phebox(-) = 1,3-bis(4,4'-dimethyl-2'-oxazolinyl)phenyl anion; L = pyridine (py), 4 phenylpyridine, quinoline, acridine) and Pt2(phebox)2(MU-L')(2+) (L' = pyrazine, 4,4'-bipyridine, 1,2-bis(4-pyridyl)ethane) was prepared. Crystallographic data establish that the metal center is bonded to the tridentate phebox(-) and monodentate pyridyl ligands. The five-membered oxazoline rings favor a CH2-CMe2 twist conformation. Pt(phebox)Cl and Pt(phebox)(py)(+) undergo a ligand-based chemically reversible redox reaction, whereas the electrochemistry of the other complexes is chemically and electrochemically less reversible. In contrast to complexes with the 1,3-bis(piperdylmethyl)phenyl anion ligand (pip2NCN(-)) or related pincer ligands, each of the phebox(-) complexes described here exhibits intense emission in room-temperature methylene chloride solution, which is assigned as originating from a lowest, predominantly phebox(-) ligand-centered excited state. In acetonitrile, the complexes undergo solvolysis resulting in displacement of the pyridyl ligands. The accumulated data demonstrate that subtle variations in the nature of the NCN and ancillary ligands of platinum(II) complexes provide access to at least five orbitally distinct emissive excited states. PMID- 26286175 TI - Nutritional Status of Rural Bengali Adolescent Boys of Tripura. PMID- 26286174 TI - Of mice and women: a comparative tissue biology perspective of breast stem cells and differentiation. AB - Tissue based research requires a background in human and veterinary pathology, developmental biology, anatomy, as well as molecular and cellular biology. This type of comparative tissue biology (CTB) expertise is necessary to tackle some of the conceptual challenges in human breast stem cell research. It is our opinion that the scarcity of CTB expertise contributed to some erroneous interpretations in tissue based research, some of which are reviewed here in the context of breast stem cells. In this article we examine the dissimilarities between mouse and human mammary tissue and suggest how these may impact stem cell studies. In addition, we consider the differences between breast ducts vs. lobules and clarify how these affect the interpretation of results in stem cell research. Lastly, we introduce a new elaboration of normal epithelial cell types in human breast and discuss how this provides a clinically useful basis for breast cancer classification. PMID- 26286176 TI - Rare Lung Diseases: Interstitial Lung Diseases and Lung Manifestations of Rheumatological Diseases. AB - The concept of Childhood Interstitial Lung Disease (ChILD) is relatively young. There has been tremendous progress in this field in the last decade. The key advance has been the recognition of interstitial lung diseases that are often distinct and occur mainly in infants. Diagnosis is challenging because the incidence is low and no single center in the world has enough cases to promote experience and clinical skills. This has led to formation of international groups of people interested in the field and the "Children's interstitial and diffuse lung disease research network" (ChILDRN) is one such group which contributed to the progress of this field. Clinically, these disorders overlap with those of other common respiratory disorders. Hence, clinical practice guidelines emphasize the additional role of chest imaging, genetic testing and lung biopsy in the diagnostic evaluation. Genetic testing, in particular, has shown tremendous progress in this field. Being noninvasive, it has the potential to help early recognition in a vast majority. Despite progress, definitive therapeutic modalities are still lacking and supportive care is still the backbone of management in the majority. Early recognition of the definitive diagnosis helps in the management, even if, in a significant number, it helps in avoiding unnecessary therapy. Also discussed in this article, is the pulmonary manifestation of rheumatic diseases in children. The incidence and spectrum of pulmonary involvement in rheumatic conditions vary and can be result of the primary disease or its management or due to an concurrent infection. PMID- 26286177 TI - The Tools of the Trade - Uses of Flexible Bronchoscopy. AB - Bronchoscopes have markedly improved the diagnosis as well as therapy in pediatric pulmonary disorders. Two types of bronchoscopes are available; flexible and rigid, with their own advantages and disadvantages. Depending on the clinical need and availability of skills, choice is made between the two. Typically, rigid scopes are largely used by the surgeons (pediatric or otolayngologists) while flexible bronchoscope stays in the domain of the pediatric pulmonologist and intensivists. Rigid scopes may be more versatile than flexible bronchoscopes in removing the foreign bodies from the airway. Flexible bronchoscopes on the other hand can even be introduced through an endotracheal tube. At times, use of both scopes may be required in a given patient for optimal results. Bronchoscopes give us a means to visualize the inside of the airway, which can be very informative for assessing various pathologies affecting the airways. Apart from the visualization of the parts of the airway tree and their structure as well as patency, it can also be used to take tissue biopsy specimens, collect secretions from the airways and bronchoalveolar lavage which can also get cellular elements from the distal alveoli. In the past few decades, more and more instruments are being used for expanding the utility of flexible bronchoscope for interventions ranging from bronchial toilet, foreign body removal, airway stenting and lasers or cryotherapy for airway lesions. The perinatologists have opened up more vistas and thrown newer challenges for using fiberoptic bronchoscopy (FB) for in utero tracheal occlusion in cases with diaphragmatic hernia. The vast applications of this tool makes it very relevant to pulmonary investigations and therapeutics. PMID- 26286178 TI - A Review of Patient Preferences for Osteoporosis Drug Treatment. AB - Poor medication adherence is a major problem in chronic diseases such as osteoporosis that may partially be due to unaddressed patient values and preferences. Data on patient preferences could help clinicians to improve medication adherence and could also be useful in policy decisions and guideline development. This paper aims to identify literature reporting on the preferences of patients for osteoporosis drug medications. Several methods have been used to elicit patient preferences for medications and their characteristics including qualitative research, survey with ranking/rating exercises, discrete-choice experiments and clinical studies (crossover designs, open-label study). All these studies revealed that osteoporotic patients have preferences for medications and their attributes, in particular for less-frequent dosing regimens. Interestingly, variations in the preferences of patients were observed in most studies, suggesting the importance to take into account individual preference in decision making to improve osteoporosis care. PMID- 26286179 TI - The ASAS Criteria for Axial Spondyloarthritis: Strengths, Weaknesses, and Proposals for a Way Forward. AB - Classification criteria should facilitate selection of similar patients for clinical and epidemiologic studies, therapeutic trials, and research on etiopathogenesis to enable comparison of results across studies from different centers. We critically appraise the validity and performance of the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial spondyloarthritis (axSpA). It is still debatable whether all patients fulfilling these criteria should be considered as having true axSpA. Patients with radiographically evident disease by the ASAS criteria are not necessarily identical with ankylosing spondylitis (AS) as classified by the modified New York criteria. The complex multi-arm selection design of the ASAS criteria induces considerable heterogeneity among patients so classified, and applying them in settings with a low prevalence of axial spondyloarthritis (SpA) greatly increases the proportion of subjects falsely classified as suffering from axial SpA. One of the unmet needs in non-radiographic form of axial SpA is to have reliable markers that can identify individuals at risk for progression to AS and thereby facilitate early intervention trials designed to prevent such progression. We suggest needed improvements of the ASAS criteria for axSpA, as all criteria sets should be regarded as dynamic concepts open to modifications or updates as our knowledge advances. PMID- 26286181 TI - [Augmented osteosynthesis]. PMID- 26286180 TI - [Civilian blast injuries: an underestimated problem? : Results of a retrospective analysis of the TraumaRegister DGU(r)]. AB - BACKGROUND: Blast injuries are a rare cause of potentially life-threatening injuries in Germany. During the past 30 years such injuries were seldom the cause of mass casualties, therefore, knowledge and skills in dealing with this type of injury are not very extensive. MATERIAL AND METHODS: A retrospective identification of all patients in the TraumaRegister DGU(r) of the German Trauma Society (TR-DGU) who sustained blast injuries between January 1993 and November 2012 was carried out. The study involved a descriptive characterization of the collective as well as three additional collectives. The arithmetic mean, standard deviation and 95 % confidence interval of the arithmetic mean for different demographic parameters and figures for prehospital and in-hospital settings were calculated. A computation of prognostic scores, such as the Revised Injury Severity Classification (RISC) and the updated version RISC II (TR-DGU-Project-ID 2012-035) was performed. RESULTS: A total of 137 patients with blast injuries could be identified in the dataset of the TR-DGU. Of the patients 90 % were male and 43 % were transported by the helicopter emergency service (HEMS) to the various trauma centres. The severely injured collective with a mean injury severity scale (ISS) of 18.0 (ISS >= 16 = 52 %) had stable vital signs. In none of the cases was it necessary to perform on-site emergency surgery but a very high proportion of patients (59 %) had to be surgically treated before admittance to the intensive care unit (ICU). Of the patients 27 % had severe soft tissue injuries with an Abbreviated Injury Scale (AIS) >= 3 and 90 % of these injuries were burns. The 24 h in-hospital fatality was very low (3 %) but the stay in the ICU tended to be longer than for other types of injury (mean 5.5 ventilation days and 10.7 days in the intensive care unit). Organ failure occurred in 36 % of the cases, multiorgan failure in 29 % and septic events in 14 %. Of the patients 16 % were transferred to another hospital during the first 48 h. The RISC and the updated RISC II tended to underestimate the severity of injuries and mortality (10.2 % vs. 6.8 % and 10.7 % vs. 7.5 %, respectively) and the trauma associated severe hemorrhage (TASH) score underestimated the probability for transfusion of more than 10 units of packed red blood cells (5.0 % vs. 12.5 %). CONCLUSION: This article generates several hypotheses, which should be confirmed with additional investigations. Until then it has to be concluded that patients who suffer from accidental blast injuries in the civilian setting (excluding military operations and terrorist attacks) show a combination of classical severe trauma with blunt and penetrating injuries and additionally a high proportion of severe burns (combined thermomechanical injury). They stay longer in the ICU than other trauma patients and suffer more complications, such as sepsis and multiorgan failure. Established scores, such as RISC, RISC II and TASH tend to underestimate the severity of the underlying trauma. PMID- 26286182 TI - Genotoxicity assessment of two common curing weeds: Hyptis suaveolens (L.) Poir. and Leucas indica (L.) R. Br. AB - Hyptis suaveolens and Leucas indica, two common weeds were selected for the present study, to reveal their probable cytotoxic potential. The meristematic root tips of Allium cepa were used for testing the cytotoxic property of the aqueous leaf extracts containing both polar and non-polar compounds, and that containing polar compounds alone, at different concentrations (0.125, 0.25, 0.5, 1 and 2 %) and at different time durations, using distilled water as negative control. Mitotic squash preparations were made using a standard protocol. The mitotic index of the treated root tip cells was found to be decreasing and the abnormality percentage was found to be increasing with increase in extract concentration when compared with the control. Maximum cytotoxicity was observed in the extract containing both polar and non-polar compounds. Both the tested plants were found to be cytotoxic. The abnormalities noticed were of both clastogenic (nuclear lesions, nuclear fragmentation, etc.) and non-clastogenic (aberrant cell wall formation at cytokinesis, ball metaphase, etc.) types. Both plant extracts were found to significantly (P < 0.05) inhibit root growth of Allium cepa with an EC50 value of 1.92 % (R(2) = 0.594) for Hyptis and 1.58 % (R(2) = 0.757) for Leucas. The results were also analysed statistically by using analysis of variance followed by appropriate post hoc tests. These two weeds are aromatic plants comprising of essential oils that are volatile, natural complex compounds characterized by a strong odour and formed as secondary metabolites. In nature, essential oils play an important role in the protection of the plants as insecticides by reducing their appetite for such plants. When specifically targeted the concept of effectively exploiting these weeds for the formulation of herbal insecticides/pesticides may be possible in the near future. PMID- 26286183 TI - Early life adversity and C-reactive protein in diverse populations of older adults: a cross-sectional analysis from the International Mobility in Aging Study (IMIAS). AB - BACKGROUND: Recent studies suggest potential associations between childhood adversity and chronic inflammation at older ages. Our aim is to compare associations between childhood health, social and economic adversity and high sensitivity C-reactive protein (hsCRP) in populations of older adults living in different countries. METHODS: We used the 2012 baseline data (n = 1340) from the International Mobility in Aging Study (IMIAS) of community-dwelling people aged 65-74 years in Natal (Brazil), Manizales (Colombia) and Canada (Kingston, Ontario; Saint-Hyacinthe, Quebec). Multiple linear and Poisson regressions with robust covariance were fitted to examine the associations between early life health, social, and economic adversity and hsCRP, controlling for age, sex, financial strain, marital status, physical activity, smoking and chronic conditions both in the Canadian and in the Latin American samples. RESULTS: Participants from Canadian cities have less adverse childhood conditions and better childhood self-reported health. Inflammation was lower in the Canadian cities than in Manizales and Natal. Significant associations were found between hsCRP and childhood social adversity in the Canadian but not in the Latin American samples. Among Canadian older adults, the fully-adjusted mean hsCRP was 2.2 (95% CI 1.7; 2.8) among those with none or one childhood social adversity compared with 2.8 (95% CI 2.1; 3.8) for those with two or more childhood social adversities (p = 0.053). Similarly, the prevalence of hsCRP > 3 mg/dL was 40% higher among those with higher childhood social adversity but after adjustment by health behaviors and chronic conditions the association was attenuated. No associations were observed between hsCRP and childhood poor health or childhood economic adversity. CONCLUSIONS: Inflammation was higher in older participants living in the Latin American cities compared with their Canadian counterparts. Childhood social adversity, not childhood economic adversity or poor health during childhood, was an independent predictor of chronic inflammation in old age in the Canadian sample. Selective survival could possibly explain the lack of association between social adversity and hsCRP in the Latin American samples. PMID- 26286184 TI - Tunable Release of Multiclass Anti-HIV Drugs that are Water-Soluble and Loaded at High Drug Content in Polyester Blended Electrospun Fibers. AB - OBJECTIVES: Sustained release of small molecule hydrophilic drugs at high doses remains difficult to achieve from electrospun fibers and limits their use in clinical applications. Here we investigate tunable release of several water soluble anti-HIV drugs from electrospun fibers fabricated with blends of two biodegradable polyesters. METHODS: Drug-loaded fibers were fabricated by electrospinning ratios of PCL and PLGA. Fiber morphology was imaged by SEM, and DSC was used to measure thermal properties. HPLC was used to measure drug loading and release from fibers. Cytotoxicity and antiviral activity of drug-loaded fibers were measured in an in vitro cell culture assay. RESULTS: We show programmable release of hydrophilic antiretroviral drugs loaded up to 40 wt%. Incremental tuning of highly-loaded drug fibers within 24 h or >30 days was achieved by controlling the ratio of PCL and PLGA. Fiber compositions containing higher PCL content yielded greater burst release whereas fibers with higher PLGA content resulted in greater sustained release kinetics. We also demonstrated that our drug-loaded fibers are safe and can sustain inhibition of HIV in vitro. CONCLUSIONS: These data suggest that we were able to overcome current limitations associated with sustained release of small molecule hydrophilic drugs at clinically relevant doses. We expect that our system represents an effective strategy to sustain delivery of water-soluble molecules that will benefit a variety of biomedical applications. PMID- 26286185 TI - Novel Gefitinib Formulation with Improved Oral Bioavailability in Treatment of A431 Skin Carcinoma. AB - PURPOSE: Oral administration of anticancer agents presents a series of advantages for patients. However, most of the anticancer drugs have poor water solubility leading to low bioavailability. METHODS: Controlled released spray dried matrix system of Gefitinib with hydroxypropyl beta-cyclodextrin, chitosan, hydroxy propyl methyl cellulose, vitamin E TPGS, succinic acid were used for the design of formulations to improve the oral absorption of Gefitinib. Spray drying with a customized spray gun which allows simultaneous/pulsatile flow of two different liquid systems through single nozzle was used to prepare Gefitinib spray dried formulations (Gef-SD). Formulation was characterized by in vitro drug release and Caco-2 permeability studies. Pharmacokinetic studies were performed in Sprague Dawley rats. Efficacy of Gef-SD was carried out in A431 xenografts models in nude mice. RESULTS: In Gef-SD group 9.14-fold increase in the AUC was observed compared to free Gef. Improved pharmacokinetic profile of Gef-SD translated into increase (1.75 fold compared to Gef free drug) in anticancer effects. Animal survival was significantly increased in Gef formulation treated groups, with superior reduction in the tumor size (1.48-fold) and volumes (1.75-fold) and also increase in the anticancer effects (TUNEL positive apoptotic cells) was observed in Gef-SD treated groups. Further, western blot, immunohistochemical and proteomics analysis demonstrated the increased pharmacodynamic effects of Gef-SD formulations in A431 xenograft tumor models. CONCLUSION: Our studies suggested that Gefitinib can be successfully incorporated into control release microparticles based oral formulation with enhanced pharmacokinetic and pharmacodynamic activity. This study demonstrates the novel application of Gef in A431 tumor models. PMID- 26286186 TI - Viscosity Analysis of Dual Variable Domain Immunoglobulin Protein Solutions: Role of Size, Electroviscous Effect and Protein-Protein Interactions. AB - PURPOSE: Increased solution viscosity results in difficulties in manufacturing and delivery of therapeutic protein formulations, increasing both the time and production costs, and leading to patient inconvenience. The solution viscosity is affected by the molecular properties of both the solute and the solvent. The purpose of this work was to investigate the effect of size, charge and protein protein interactions on the viscosity of Dual Variable Domain Immunoglobulin (DVD Ig(TM)) protein solutions. METHODS: The effect of size of the protein molecule on solution viscosity was investigated by measuring intrinsic viscosity and excluded volume calculations for monoclonal antibody (mAb) and DVD-Ig(TM) protein solutions. The role of the electrostatic charge resulting in electroviscous effects for DVD-Ig(TM) protein was assessed by measuring zeta potential. Light scattering measurements were performed to detect protein-protein interactions affecting solution viscosity. RESULTS: DVD-Ig(TM) protein exhibited significantly higher viscosity compared to mAb. Intrinsic viscosity and excluded volume calculations indicated that the size of the molecule affects viscosity significantly at higher concentrations, while the effect was minimal at intermediate concentrations. Electroviscous contribution to the viscosity of DVD Ig(TM) protein varied depending on the presence or absence of ions in the solution. In buffered solutions, negative k D and B 2 values indicated the presence of attractive interactions which resulted in high viscosity for DVD Ig(TM) protein at certain pH and ionic strength conditions. CONCLUSIONS: Results show that more than one factor contributes to the increased viscosity of DVD Ig(TM) protein and interplay of these factors modulates the overall viscosity behavior of the solution, especially at higher concentrations. PMID- 26286187 TI - The Effect of Excipients on the Permeability of BCS Class III Compounds and Implications for Biowaivers. AB - PURPOSE: Currently, the FDA allows biowaivers for Class I (high solubility and high permeability) and Class III (high solubility and low permeability) compounds of the Biopharmaceutics Classification System (BCS). Scientific evidence should be provided to support biowaivers for BCS Class I and Class III (high solubility and low permeability) compounds. METHODS: Data on the effects of excipients on drug permeability are needed to demonstrate that commonly used excipients do not affect the permeability of BCS Class III compounds, which would support the application of biowaivers to Class III compounds. This study was designed to generate such data by assessing the permeability of four BCS Class III compounds and one Class I compound in the presence and absence of five commonly used excipients. RESULTS: The permeability of each of the compounds was assessed, at three to five concentrations, with each excipient in two different models: Caco-2 cell monolayers, and in situ rat intestinal perfusion. No substantial increases in the permeability of any of the compounds were observed in the presence of any of the tested excipients in either of the models, with the exception of disruption of Caco-2 cell monolayer integrity by sodium lauryl sulfate at 0.1 mg/ml and higher. CONCLUSION: The results suggest that the absorption of these four BCS Class III compounds would not be greatly affected by the tested excipients. This may have implications in supporting biowaivers for BCS Class III compounds in general. PMID- 26286188 TI - The Evaluation of the Therapeutic Efficacy and Side Effects of a Macromolecular Dexamethasone Prodrug in the Collagen-Induced Arthritis Mouse Model. AB - PURPOSE: To investigate the efficacy and safety of N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-dexamethasone conjugate (P-Dex) in the collagen induced arthritis (CIA) mouse model. METHODS: HPMA copolymer labeled with a near infrared fluorescence (NIRF) dye was administered to mice with CIA to validate its passive targeting to inflamed joints and utility as a drug carrier system. The CIA mice were treated with P-Dex, dexamethasone (Dex) or saline and the therapeutic efficacy and skeletal toxicity evaluated using clinical scoring and micro-computed tomography (MU-CT). RESULTS: The NIRF signal of the HPMA copolymer localized to arthritic joints consistent with its passive targeting to sites of inflammation. While the CIA mice responded more rapidly to P-Dex compared to Dex, the final clinical score and endpoint MU-CT analyses of localized bone erosions indicated that both single dose P-Dex and dose equivalent daily Dex led to comparable clinical efficacy after 30 days. MU-CT analysis of the proximal tibial metaphyses showed that P-Dex treatment was associated with significantly higher BMD and BV/TV compared to Dex and the saline control, consistent with reduced glucocorticoid (GC) skeletal toxicity. CONCLUSION: These results validate the therapeutic efficacy of P-Dex in the CIA mouse model. P-Dex treatment averted the adverse effects of GC's on systemic bone loss, supporting its utility in clinical development for the management of rheumatoid arthritis. PMID- 26286189 TI - Alginate dressings for venous leg ulcers. AB - BACKGROUND: Venous leg ulcers are a common and recurring type of chronic, complex wound associated with considerable cost to patients and healthcare providers. To aid healing, primary wound contact dressings are usually applied to ulcers beneath compression devices. Alginate dressings are used frequently and there is a variety of alginate products on the market, however, the evidence base to guide dressing choice is sparse. OBJECTIVES: To determine the effects of alginate dressings compared with alternative dressings, non-dressing treatments or no dressing, with or without concurrent compression therapy, on the healing of venous leg ulcers. SEARCH METHODS: For this first update, in March 2015, we searched the following databases: The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions based on language or date of publication. SELECTION CRITERIA: Published or unpublished randomised controlled trials (RCTs) that evaluated the effects of any type of alginate dressing in the treatment of venous ulcers were included. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, data extraction and risk of bias assessment. Meta-analysis was undertaken when deemed feasible and appropriate. MAIN RESULTS: Five RCTs (295 participants) were included in this review. All were identified during the original review. The overall risk of bias was high for two RCTs and unclear for three. One RCT compared different proprietary alginate dressings (20 participants), three compared alginate and hydrocolloid dressings (215 participants), and one compared alginate and plain non-adherent dressings (60 participants). Follow-up periods were six weeks in three RCTs and 12 weeks in two. No statistically significant between-group differences were detected for any comparison, for any healing outcome. Meta-analysis was feasible for one comparison (alginate and hydrocolloid dressings), with data from two RCTs (84 participants) pooled for complete healing at six weeks: risk ratio 0.42 (95% confidence interval 0.14 to 1.21). Adverse event profiles were generally similar between groups (not assessed for alginate versus plain non-adherent dressings). AUTHORS' CONCLUSIONS: The current evidence base does not suggest that alginate dressings are more or less effective in the healing of venous leg ulcers than hydrocolloid or plain non-adherent dressings, and there is no evidence to indicate a difference between different proprietary alginate dressings. However, the RCTs in this area are considered to be of low or unclear methodological quality. Further, good quality evidence is required from well designed and rigorously conducted RCTs that employ - and clearly report on - methods to minimise bias, prior to any definitive conclusions being made regarding the efficacy of alginate dressings in the management of venous leg ulcers. PMID- 26286190 TI - [Overcoming disease in systemic lupus erythematosus]. AB - BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease affecting a broad range of different organ systems and, hence, presenting with multiple symptomatic domains, which considerably reduces the quality of life of patients. Within the last decade the prognosis of the disease has been significantly improved by novel therapies and intensive monitoring; however, non-pharmaceutical strategies for symptom control, self-efficacy and coping abilities for those affected are still insufficiently established. OBJECTIVE: This article describes the possibilities and limitations of non pharmaceutical strategies and makes suggestions for future treatment and research. RESULTS: Preliminary interventional studies using psychoeducational, psychosocial and behavioral psychotherapeutic approaches, have consistently shown that the needs and expectations of patients related to help and support by doctors and professional care can be adequately and sustainably met. In addition, coping abilities and the quality of life can be increased. PMID- 26286191 TI - Proadrenomedullin and copeptin in pediatric pneumonia: a prospective diagnostic accuracy study. AB - BACKGROUND: Community-acquired-pneumonia is the leading cause of child mortality worldwide. Very few studies have explored the predictive value of Proadrenomedullin and Copeptin in pediatric severe pneumonia and bacteremia. METHODS: Proadrenomedullin and Copeptin were assessed as predictors for complicated community-acquired pneumonia (bacteremia, empyema) in 88 children aged 0 to 16 years presenting to the pediatric emergency department, using B.R.A.H.M.S. Kryptor Compact pro-ADM and Copeptin with the TRACE technology (time resolved amplified cryptase emission). STARD standard reporting was used. RESULTS: A complicated community-acquired pneumonia was found in 11 out of 88 children (12.5 %). Proadrenomedullin median values increased more than twofold, in complicated vs. uncomplicated (0.18 vs. 0.08 nmol/L, p = 0.039), and fivefold in bacteremic vs. non-bacteremic pneumonia (0.40 vs. 0.08 nmol/L, p = 0.02). Proadrenomedullin > 0.16 nmol/L showed 100 % sensitivity (95 % CI 39.8 - 100.0) and 70 % (95 % CI 58.7 - 79.7) specificity for bacteremia. Copeptin showed no added-value. CONCLUSIONS: Proadrenomedullin seems a reliable and available predictor for complicated CAP, and could therefore help the physician with the decision to hospitalize, and choose the antibiotics administration route. Larger studies are needed. PMID- 26286192 TI - Involvement of SRSF11 in cell cycle-specific recruitment of telomerase to telomeres at nuclear speckles. AB - Telomerase, a unique ribonucleoprotein complex that contains the telomerase reverse transcriptase (TERT), the telomerase RNA component (TERC) and the TERC binding protein dyskerin, is required for continued cell proliferation in stem cells and cancer cells. Here we identify SRSF11 as a novel TERC-binding protein that localizes to nuclear speckles, subnuclear structures that are enriched in pre-messenger RNA splicing factors. SRSF11 associates with active telomerase enzyme through an interaction with TERC and directs it to nuclear speckles specifically during S phase of the cell cycle. On the other hand, a subset of telomeres is shown to be constitutively present at nuclear speckles irrespective of cell cycle phase, suggesting that nuclear speckles could be the nuclear sites for telomerase recruitment to telomeres. SRSF11 also associates with telomeres through an interaction with TRF2, which facilitates translocation of telomerase to telomeres. Depletion of SRSF11 prevents telomerase from associating with nuclear speckles and disrupts telomerase recruitment to telomeres, thereby abrogating telomere elongation by telomerase. These findings suggest that SRSF11 acts as a nuclear speckle-targeting factor that is essential for telomerase association with telomeres through the interactions with TERC and TRF2, and provides a potential target for modulating telomerase activity in cancer. PMID- 26286193 TI - Role of a non-canonical surface of Rad6 in ubiquitin conjugating activity. AB - Rad6 is a yeast E2 ubiquitin conjugating enzyme that monoubiquitinates histone H2B in conjunction with the E3, Bre1, but can non-specifically modify histones on its own. We determined the crystal structure of a Rad6~Ub thioester mimic, which revealed a network of interactions in the crystal in which the ubiquitin in one conjugate contacts Rad6 in another. The region of Rad6 contacted is located on the distal face of Rad6 opposite the active site, but differs from the canonical E2 backside that mediates free ubiquitin binding and polyubiquitination activity in other E2 enzymes. We find that free ubiquitin interacts weakly with both non canonical and canonical backside residues of Rad6 and that mutations of non canonical residues have deleterious effects on Rad6 activity comparable to those observed to mutations in the canonical E2 backside. The effect of non-canonical backside mutations is similar in the presence and absence of Bre1, indicating that contacts with non-canonical backside residues govern the intrinsic activity of Rad6. Our findings shed light on the determinants of intrinsic Rad6 activity and reveal new ways in which contacts with an E2 backside can regulate ubiquitin conjugating activity. PMID- 26286194 TI - Carbohydrate structure database merged from bacterial, archaeal, plant and fungal parts. AB - The Carbohydrate Structure Databases (CSDBs, http://csdb.glycoscience.ru) store structural, bibliographic, taxonomic, NMR spectroscopic, and other data on natural carbohydrates and their derivatives published in the scientific literature. The CSDB project was launched in 2005 for bacterial saccharides (as BCSDB). Currently, it includes two parts, the Bacterial CSDB and the Plant&Fungal CSDB. In March 2015, these databases were merged to the single CSDB. The combined CSDB includes information on bacterial and archaeal glycans and derivatives (the coverage is close to complete), as well as on plant and fungal glycans and glycoconjugates (almost all structures published up to 1998). CSDB is regularly updated via manual expert annotation of original publications. Both newly annotated data and data imported from other databases are manually curated. The CSDB data are exportable in a number of modern formats, such as GlycoRDF. CSDB provides additional services for simulation of (1)H, (13)C and 2D NMR spectra of saccharides, NMR-based structure prediction, glycan-based taxon clustering and other. PMID- 26286195 TI - Adrenocortical Carcinoma: Impact of Surgical Margin Status on Long-Term Outcomes. AB - BACKGROUND: The influence of surgical margin status on long-term outcomes of patients undergoing adrenal resection for ACC remains not well defined. We studied the impact of surgical tumor margin status on recurrence-free survival (RFS) and overall survival (OS) of patients undergoing resection for ACC. METHODS: A total of 165 patients who underwent adrenal resection for ACC and met inclusion criteria were identified form a multi-institutional database. Clinicopathological data, pathologic margin status, and long-term outcomes were assessed. Patients were stratified into two groups based on margin status: R0 (margin >1 mm) versus R1. RESULTS: R0 resection was achieved in 126 patients (76.4 %), whereas 39 patients (23.6 %) had an R1 resection. Median and 5-year OS for patients undergoing R0 resection were 96.3 months and 64.8 % versus 25.1 months and 33.8 % for patients undergoing an R1 resection (both p < 0.001). On multivariable analysis, surgical margin status was an independent predictor of worse OS (hazard ratio [HR] 2.22, 95 % confidence interval [CI] 1.03-4.77; p = 0.04). The incidence of recurrence also differed between the two groups; 5-year RFS was 30.3 % among patients with an R0 resection versus 13.8 % among patients who had an R1 resection (p = 0.03). Lymph node metastasis (N1) was an independent predictor of RFS (HR 2.70, 95 % CI 1.04-6.99; p = 0.04). CONCLUSIONS: A positive margin after ACC resection was associated with worse long-term survival. Patient selection and an emphasis on surgical technique to achieve R0 margins are pivotal to optimizing the best chance for long-term outcome among patients with ACC. PMID- 26286196 TI - HPV and EBV Infections in Neck Metastases from Occult Primary Squamous Cell Carcinoma: Another Virus-Related Neoplastic Disease in the Head and Neck Region. AB - BACKGROUND: Approximately 1-9 % of all head and neck squamous cell carcinomas are neck metastases from clinically undetectable primary tumors. Human papillomavirus (HPV) and Epstein-Barr virus (EBV) are proven carcinogenic factors that are associated with oropharyngeal squamous cell carcinoma and nasopharyngeal carcinoma, respectively. In the present study, we evaluated the prevalence of these viruses in neck metastases from unknown primary squamous cell carcinoma. METHODS: We evaluated fresh samples from a consecutive series of 22 neck dissections for metastases from unknown primary squamous cell carcinoma obtained between 2010 and 2012 at a single institution. The samples were tested for the presence of HPV E6 and E7 mRNA and EBV DNA. RESULTS: Oncogenic viral infections were detected in 12 cases (54 % total; 2 HPV18, 5 HPV16, 2 EBV infection, and 3 EBV/HPV16 coinfections). The most frequent primarily involved neck level in our series was IIA (70 %), which had the highest prevalence of viral infection (66 %). We did not find any other significant correlations between virus detection and clinicopathologic parameters or prognosis. DISCUSSION: Neck metastasis from unknown primary squamous cell carcinoma could be another virus-related malignancy in the head and neck region, along with nasopharyngeal and oropharyngeal carcinoma. An evaluation of the impact of viral infection on patient prognosis and sensitivities to different treatment modalities could modify our prognostic assessments and treatment planning. Furthermore, virus detection would have a decisive impact on diagnostic/decisional algorithms, especially if detection methods are implemented on cytologic samples (e.g., thin prep). PMID- 26286197 TI - Radiotherapy and Conservative Surgery in the Locoregional Management of Merkel Cell Carcinoma: The British Columbia Cancer Agency Experience. AB - BACKGROUND: Merkel cell carcinoma (MCC) is an uncommon aggressive skin malignancy. Published series mainly focus on wide excision, which can be difficult at some sites (e.g., face) and in patients with comorbidities. In British Columbia, an approach of conservative surgery followed by radiotherapy is common. MATERIALS AND METHODS: This is a retrospective review of 179 patients treated for MCC with curative intent in British Columbia. RESULTS: Totals of 68, 63, and 37 patients underwent narrow excision of primary, attempted wide excision, and biopsy only, respectively. Adjuvant radiotherapy reduced local recurrence after narrow excision (<10 mm margin) from 25 to 4.9 % (p = .03) and was effective in the presence of microscopic positive margins. Local recurrence rate was 7.1 % if the margin was >10 mm irrespective of radiation use. Local RFS was improved by adjuvant radiation therapy (RT) (p = 0.04), and there was a trend to reduced nodal relapse after elective nodal RT (p = .07). Irradiation of macroscopic tumor at 37 primary and 33 nodal sites provided 5-year local and nodal RFS of 90 and 75 %, respectively. The 5-year cancer specific survival was 77 % and was not improved by the use of adjuvant radiotherapy. CONCLUSIONS: Local excision plus adjuvant RT is an effective treatment for MCC. Adjuvant radiation should be considered when the excision margin is <1 cm. PMID- 26286198 TI - Prognostic Significance of Sarcomatous Change in Patients with Hepatocellular Carcinoma After Surgical Resection. AB - BACKGROUND: Hepatocellular carcinoma (HCC) with sarcomatous change (SC) is a rare malignancy associated with high aggressiveness and poor prognosis; however, its prognostic significance remains unclear. METHODS: From January 1994 to April 2012, surgically resected HCCs with SC (n = 52) at West China Hospital were retrospectively reviewed. HCC with SC was defined as the concomitant presence of the sarcomatous component occupying at least 10 % (but not predominantly) of the HCC-bearing tissue. To validate its prognostic significance, we compared the clinicopathological features and survival rates of these patients with a cohort of 214 randomly selected ordinary HCC patients during the same period. RESULTS: The clinicopathological characteristics of HCC with SC were similar to those of ordinary HCC, with the exception of capsule formation, adjacent organ invasion, lymph node metastasis, and TNM staging. A total of 45 (86.5 %) HCC patients with SC experienced a recurrence, with a median time to recurrence of 6.0 months. Overall survival (OS) rates in the sarcomatous HCC group at 1, 2, and 3 years were 55.8, 25, and 17.3 %, respectively, which were significantly lower than those in the ordinary HCC group (p < 0.001). On multivariable analysis, macrovascular invasion, satellite nodules, and R1/R2 resection were identified as independent risk factors for shorter disease-free survival and OS. CONCLUSIONS: The presence of SC in HCC was uncommon, and was associated with much poorer prognosis than ordinary HCC. Radical resection with negative margin is essential for improving the prognosis. Future prospective studies are warranted to determine if recurrent patients can benefit from postoperative adjuvant therapies. PMID- 26286200 TI - Chyle Fistula After Neck Dissection: An 8-Year, Single-Center, Prospective Study of Incidence, Clinical Features, and Treatment. AB - BACKGROUND: Chyle fistula is a relatively rare complication of neck dissection, and there is a lack of consensus regarding its incidence, risk factors, and management. METHODS: Between 2007 and 2014, a total of 472 cases of neck dissection involving the level IV compartment were included in the study. The incidence, risk factors, and clinical course of chyle fistula were investigated, as well as the outcomes of conventional management and the use of octreotide injection in high-output chyle fistula. RESULTS: The overall incidence of chyle fistula was 4.7 % (22/472), with an incidence of 3.0 % and 6.2 % after right and left neck dissection, respectively. The presence of a metastatic lesion around the junction of the internal jugular vein and subclavian vein was the only factor significantly associated with the development of chyle fistula (approximately fourfold higher risk) in univariate and multivariate analyses. In 22 cases of chyle fistula, the mean total drainage volume was 3226 mL during a mean 15.4 days of drain placement. Total parental nutrition for the management of chyle fistula was required in 16 cases. Nine (40.9 %) of 22 cases experienced additional complications related to chyle fistula. Of the six high-output cases, four were managed with conservative methods plus octreotide injection, and three did not require surgery. CONCLUSIONS: The incidence of chyle fistula after neck dissection was higher than expected, especially on the right side. Surgeons should pay greater attention to chyle fistula from preoperative evaluation to postoperative management. PMID- 26286199 TI - Prevalence of Malnutrition Among Gastric Cancer Patients Undergoing Gastrectomy and Optimal Preoperative Nutritional Support for Preventing Surgical Site Infections. AB - BACKGROUND: Malnutrition is an independent risk factor for postoperative mortality and morbidity in major gastrointestinal surgery. The aim of this study was to investigate the prevalence of malnutrition and identify the optimal preoperative nutritional support for preventing postoperative surgical site infections (SSIs) in malnourished gastric cancer patients undergoing gastrectomy. METHODS: We analyzed 800 patients with gastric cancer who underwent gastrectomy. Nutritional risk factors included weight loss >10 % within 6 months, body mass index <18.5 kg/m(2), Subjective Global Assessment Grade C, and serum albumin <3.0 g/dl. Adequate energy intake was defined as receiving >=25 kcal/kg ideal body weight per day. Optimal nutritional support was examined in terms of both duration and calorie intake. RESULTS: Overall, 152 patients (19.0 %) were classified as malnourished. The incidence of SSIs was significantly higher in malnourished patients than in well-nourished patients (35.5 vs. 14.0 %; p < 0.0001). The incidence of SSIs in malnourished patients was significantly lower in the well-supported group receiving adequate energy support for at least 10 days than in the poorly-supported group, which received inadequate or no energy support or adequate energy support for <10 days (17.0 vs. 45.4 %; p = 0.0006). In multivariate analysis, well-managed nutritional support was identified as an independent factor associated with fewer SSIs (odds ratio 0.14; 95 % confidence interval 0.05-0.37; p = 0.0002). CONCLUSIONS: Malnutrition, a risk factor for SSI, was prevalent in gastric cancer patients preoperatively. Well-managed preoperative nutritional support decreased the incidence of postoperative SSIs in malnourished patients. PMID- 26286201 TI - Comparison of discrete ratios by rhesus macaques (Macaca mulatta). AB - Perceiving and comparing ratios are crucial skills for humans. Little is known about whether other animals can compare ratios. We trained two rhesus macaques (Macaca mulatta) to choose arrays that contained the greater ratio of positive to negative stimuli, regardless of the absolute number of stimuli in each of the two choice arrays. Subjects learned this task, and their performance generalized to novel ratios. Moreover, performance was modulated by the ratio between ratios; subjects responded more quickly and accurately when the ratio between ratios was higher. Control conditions ruled out the possibility that subjects were relying on surface area, although the ratio between ratios of surface area did seem to influence their choices. Our results demonstrate that rhesus monkeys can compare discrete ratios, demonstrating not only proportional reasoning ability but also the ability to reason about relations between relations. PMID- 26286202 TI - Early Benefit Assessments in Oncology in Germany: How Can a Clinically Relevant Endpoint Not Be Relevant to Patients? AB - After 4 years of early benefit assessment (EBA) in Germany, it is becoming evident that the Federal Joint Committee (FJC) frequently considers well established clinical endpoints as not being relevant to patients. Focusing on assessments of oncology medicines, we analysed the FJC's view on primary endpoints and compared it with the approach used by regulatory authorities. Mortality data were accepted by both stakeholders. Whereas regulatory authorities accepted primary morbidity endpoints such as progression-free survival and response rates, the FJC mostly excluded these from its assessments. Health related quality of life (HRQoL) data have been poorly reflected in the approval process; for EBAs, those data have rarely impacted on benefit ratings. We argue that agreement between regulatory authorities and the FJC is required regarding primary study endpoints that are relevant to patients, and that clarification of acceptable endpoints by the FJC, especially in the morbidity domain, has to be provided. Moreover, in order to fully acknowledge the benefit of a new medicinal product, mortality, morbidity and HRQoL should be weighted differentially, according to the condition. PMID- 26286203 TI - Population Pharmacokinetics and Pharmacodynamics of GSK961081 (Batefenterol), a Muscarinic Antagonist and beta2-Agonist, in Moderate-to-Severe COPD Patients: Substudy of a Randomized Trial. AB - GSK961081 (batefenterol) is a novel bifunctional molecule composed of a muscarinic antagonist and a beta2-agonist. The aims of this substudy were (1) to characterize the population pharmacokinetics (PK) and pharmacodynamics (PD) of GSK961081 in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD); and (2) to investigate the relationship between systemic exposure to GSK961081 and key cardiac-related safety parameters. Three once-daily doses (100, 400, and 800 MUg) and three twice-daily doses (100, 200, and 400 MUg) of GSK961081 DISKUS were investigated. A two-compartment disposition PK model with first-order absorption adequately described the plasma GSK961081 concentration time data. An empirical maximum-effects PD model adequately described the forced expiratory volume in 1 s (FEV1) response relationship with the covariate baseline FEV1 on day 1. No clear relationships between GSK961081 plasma drug levels and cardiac-related safety parameters were apparent. The PK and PD models will be used to guide the dose selection and development of GSK961081 in patients with COPD. PMID- 26286204 TI - Regime shifts and resilience in China's coastal ecosystems. AB - Regime shift often results in large, abrupt, and persistent changes in the provision of ecosystem services and can therefore have significant impacts on human wellbeing. Understanding regime shifts has profound implications for ecosystem recovery and management. China's coastal ecosystems have experienced substantial deterioration within the past decades, at a scale and speed the world has never seen before. Yet, information about this coastal ecosystem change from a dynamics perspective is quite limited. In this review, I synthesize existing information on coastal ecosystem regime shifts in China and discuss their interactions and cascading effects. The accumulation of regime shifts in China's coastal ecosystems suggests that the desired system resilience has been profoundly eroded, increasing the potential of abrupt shifts to undesirable states at a larger scale, especially given multiple escalating pressures. Policy and management strategies need to incorporate resilience approaches in order to cope with future challenges and avoid major losses in China's coastal ecosystem services. PMID- 26286206 TI - Use of perampanel in one case of super-refractory hypoxic myoclonic status: Case report. AB - Proper treatment of hypoxic myoclonic status is not clearly determined. Induced hypothermia is improving prognosis and a more aggressive treatment might be beneficial in some patients. Among the new options of antiepileptic drugs, perampanel (PER) is a drug with a novel mechanism, and it might be a promising drug for myoclonic status or as an antimyoclonic drug. We describe the use of PER in one patient with hypoxic super-refractory myoclonic status. DESCRIPTION: A 51 year-old patient presented after an out-of-hospital cardiac arrest due to an acute myocardial infarction. The patient was diagnosed with clinical and electrical (EEG) myoclonic status at the rewarming phase. Several treatments were used, starting with clonazepam, valproate, sedation (midazolam, propofol), and subsequently barbiturate-induced coma with persistent myoclonic status. Finally, we decided to try PER (dose: 6-8 mg) through a nasogastric tube, resulting in a marked improvement of EEG activity and myoclonus decrease. The patient had a progressive clinical improvement, with a CPC (Cerebral Performance Category) scale score of 1. CONCLUSION: This case shows the potential utility of PER as a therapeutic option in super-refractory hypoxic status and even its potential use before other aggressive alternatives considering their greater morbidity. PMID- 26286205 TI - Selective Impairment of Spatial Cognition Caused by Autoantibodies to the N Methyl-D-Aspartate Receptor. AB - Patients with systemic lupus erythematosus (SLE) experience cognitive abnormalities in multiple domains including processing speed, executive function, and memory. Here we show that SLE patients carrying antibodies that bind DNA and the GluN2A and GluN2B subunits of the N-methyl-d-aspartate receptor (NMDAR), termed DNRAbs, displayed a selective impairment in spatial recall. Neural recordings in a mouse model of SLE, in which circulating DNRAbs penetrate the hippocampus, revealed that CA1 place cells exhibited a significant expansion in place field size. Structural analysis showed that hippocampal pyramidal cells had substantial reductions in their dendritic processes and spines. Strikingly, these abnormalities became evident at a time when DNRAbs were no longer detectable in the hippocampus. These results suggest that antibody-mediated neurocognitive impairments may be highly specific, and that spatial cognition may be particularly vulnerable to DNRAb-mediated structural and functional injury to hippocampal cells that evolves after the triggering insult is no longer present. PMID- 26286207 TI - Regulation of Gene Expression by Sodium Valproate in Epithelial-to-Mesenchymal Transition. AB - PURPOSE: Epithelial-to-mesenchymal transition (EMT) is an important mechanism in cancer metastasis and pulmonary fibrosis. Previous studies demonstrated effect of histone H3 and H4 acetylation in cancer and pulmonary fibrosis, so we hypothesized that histone modification might play a crucial role in gene regulation during EMT. In this study, we investigated the mechanism behind EMT by analyzing comprehensive gene expression and the effect of sodium valproate (VPA), a class I histone deacetylase inhibitory drug, on histone modification. METHODS: EMT was induced in human alveolar epithelial cells (A549) using 5 ng/mL of transforming growth factor (TGF)-beta1. Various concentrations of VPA were then administered, and Western blotting was used to analyze histone acetylation or methylation. Comprehensive gene expression analysis was carried out by RNA sequencing, and chromatin immunoprecipitation was performed with an anti-acetyl histone H3 lysine 27 antibody. RESULTS: TGF-beta1 stimulation led to a decrease in histone acetylation, especially that of histone H3K27, and H3K27ac localization was decreased at particular gene loci. This decrease was recovered by VPA treatment, which also up-regulated the mRNA expression of genes down regulated by TGF-beta1, and correlated with the localization of H3K27ac. However, genes up-regulated by TGF-beta1 stimulation were not suppressed by VPA, with the exception of COL1A1. CONCLUSIONS: Histone acetylation was down-regulated by TGF beta1 stimulation in A549 cells. VPA partially inhibited EMT and the decrease of histone acetylation, which plays an important role in the progression of EMT. PMID- 26286208 TI - Benefits of Physical Training in Sarcoidosis. AB - BACKGROUND: Sarcoidosis patients suffer from fatigue and exercise limitation. The aim of this study was to establish whether a physical training program improves these and other outcomes important to sarcoidosis patients. METHODS: From 11/2012 to 9/2014, 201 sarcoidosis patients were referred to the ild care expertise team, Ede, the Netherlands. In our center, all patients are routinely recommended to undergo testing at baseline to determine their physical functioning and encouraged to complete a 12-week, supervised physical training program. Ninety patients underwent baseline testing and returned for repeat testing at 3 months in the interim, 49 completed the training program (Group I) and 41 chose not to participate (Group II). Change over time (from baseline to 3 months) in fatigue, exercise capacity, and skeletal muscle strength were assessed between the two groups. RESULTS: At baseline, there were no between-group differences for fatigue, DLCO%, FVC%, or exercise capacity [assessed by percent predicted six minute walk distance (6MWD%) and Steep Ramp Test (SRT)]. The 6MWD for Group I improved between baseline and 3 months, while the 6MWD remained the same in Group II (F = 72.2, p < 0.001). Group I showed a significantly larger decrease of fatigue compared with Group II (F = 6.27, p = 0.014). Lung function tests did not change in either group. CONCLUSION: A supervised physical training program improves exercise capacity and fatigue among sarcoidosis patients and should be included in their management regimen. PMID- 26286210 TI - Prediction and Dissection of Protein-RNA Interactions by Molecular Descriptors. AB - Protein-RNA interactions play crucial roles in numerous biological processes. However, detecting the interactions and binding sites between protein and RNA by traditional experiments is still time consuming and labor costing. Thus, it is of importance to develop bioinformatics methods for predicting protein-RNA interactions and binding sites. Accurate prediction of protein-RNA interactions and recognitions will highly benefit to decipher the interaction mechanisms between protein and RNA, as well as to improve the RNA-related protein engineering and drug design. In this work, we summarize the current bioinformatics strategies of predicting protein-RNA interactions and dissecting protein-RNA interaction mechanisms from local structure binding motifs. In particular, we focus on the feature-based machine learning methods, in which the molecular descriptors of protein and RNA are extracted and integrated as feature vectors of representing the interaction events and recognition residues. In addition, the available methods are classified and compared comprehensively. The molecular descriptors are expected to elucidate the binding mechanisms of protein RNA interaction and reveal the functional implications from structural complementary perspective. PMID- 26286209 TI - IQGAP3 is essential for cell proliferation and motility during zebrafish embryonic development. AB - IQGAPs are scaffolding proteins that regulate actin assembly, exocyst function, cell motility, morphogenesis, adhesion and division. Vertebrates express 3 family members: IQGAP1, IQGAP2, and IQGAP3. IQGAP1 is known to stimulate nucleation of branched actin filaments through N-WASP and the Arp2/3 complex following direct binding to cytoplasmic tails of ligand-activated growth factor receptors, including EGFR, VEGFR2 and FGFR1. By contrast, little is known about functions of IQGAP2 or IQGAP3. Using in situ hybridization on whole mount zebrafish (Danio rerio) embryos, we show that IQGAP1 and IQGAP2 are associated with discrete tissues and organs, while IQGAP3 is mainly expressed in proliferative cells throughout embryonic and larval development. Morpholino knockdowns of IQGAP1 and IQGAP2 have little effect on embryo morphology while loss of function of IQGAP3 affects both cell proliferation and cell motility. IQGAP3 morphant phenotypes are similar to those resulting from overexpression of dominant negative forms of Ras or of Fibroblast Growth Factor Receptor 1 (FGFR1), suggesting that IQGAP3 plays a role in FGFR1-Ras-ERK signaling. In support of this hypothesis, dominant negative forms of FGFR1 or Ras could be rescued by co-injection of zebrafish IQGAP3 mRNA, strongly suggesting that IQGAP3 acts as a downstream regulator of the FGFR1-Ras signaling pathway. PMID- 26286212 TI - Interplay between Catalysts and Substrates for Activity of Class Ib Aminoacyl tRNA Synthetases and Implications for Pharmacology. AB - Aminoacyl-tRNA synthetase:transfer RNA (aaRS:tRNA) systems became recently essential targets in molecular medicine, because perturbed recognition of cognate tRNAs by aaRSs and poor precision in tRNA aminoacylation do not guarantee accurate protein biosynthesis, thus leading to diseases. Sets of identity determinants situated at particular zones of tRNA are responsible for functional accuracy. Recent work in X-ray crystallography has revealed various snapshots of aaRS:ligand complexes which represent the stages required for aminoacylation. Here we focus on a small group of class I aaRSs conserved in evolution, the ArgRSs, GluRSs, GlnRSs, and atypical LysRSs found mostly in Archaea and in a few Bacteria, that catalyze amino acid activation only in the presence of their cognate tRNAs. Structural and functional features of these aaRSs, ranked in subclass Ib, together with their peculiar mode of tRNA recognition and identity expression are reviewed and compared. Strategies to inhibit class Ib aaRS:tRNA aminoacylation systems, their dysfunction leading to human diseases, and the implications for pharmacology are outlined. PMID- 26286211 TI - Recent Progress in Predicting Posttranslational Modification Sites in Proteins. AB - The posttranslational modification or PTM is a later but subtle step in protein biosynthesis via which to change the properties of a protein by adding a modified group to its one or more amino acid residues. PTMs are responsible for many significant biological processes, and meanwhile for many major diseases as well, such as cancer. Facing the avalanche of biological sequences generated in the post-genomic age, it is important for both basic research and drug development to timely identify the PTM sites in proteins. This Review is devoted to summarize the recent progresses in this area, with a focus on those predictors, which were developed based on the pseudo amino acid composition or PseAAC approach, and for which a publicly accessible web-server has been established. Meanwhile, the future challenge in this area has also been briefly addressed. PMID- 26286213 TI - A New Insight of Herbal Promises Against Ocular Disorders: An Occuloinformatics Approach. AB - Ocular biology is a prominent area of research and advancement, as eyes are the most precious for us to see this beautiful world. Though we have overcome many ocular problems, but still challenges, no doubt exist in the path of the journey. Many ocular disorders still either have surgery or symptomatic drugs as a treatment. If we could get a better preventive way or single drug with many and more potential effects, will definitely be a boon for our society. Keeping the way we tried to focus on the impending effects of phytochemicals on some important ocular disorders. Our study promised with virtual screening based on important insilico protocols that can be a landmark for better futuristic approach towards novel drug development. As a selection Eales' Disease, Diabetic Retinopathy, Uveitis, Age related Macular Disorder, CRVO were taken. Causative Protein identification is the basic of study and further advance Insilico approaches were based on this target in respective disorders. Retinol Binding protein-3 and Retinal S antigen protein in case of Eales, Erythropoietin in the case of Diabetic Retinopathy, Nucleotide-binding oligomerization domain containing protein-2 in case of Uveitis, Hemicentin-1 in case of Age related Macular Disorder, Coagulation Factor-V in case of CRVO were identified. Insilico characterization, Secondary and Tertiary structure prediction makes the study more prominent towards virtual screening. Virtual Screening was based on the parameters of docking, which reflects the potentiality of Ginkgolide, D-pinitol, Gugglesterones, Berberine and Curcumin herbal molecules against above mentioned ocular disorders respectively. Study signifies about the spectacular vision of herbal uses just to limit the vast side effects of synthetic chemicals used as ocular drugs. PMID- 26286214 TI - Modulation of Cytokine Network in the Comorbidity of Schizophrenia and Tuberculosis. AB - Schizophrenia is a severe complex disabling disease that has impaired about 1% of the total population. It is widely recognized that schizophrenia is caused by the abnormal immune system. However, the current genome-wide association study (GWAS) of schizophrenia did not identify any cytokine molecules except genes in the major histocompatibility complex (MHC) region, suggesting that new strategies are needed to find out the effects of cytokines during the development of Schizophrenia. Recently, increasing evidences have found the comorbidity of schizophrenia with tuberculosis. To narrow down the scope of cytokines and reveal the core culprit, we first systematically review the common cytokines between these two diseases, followed by summarizing the core cytokines' interaction and modulation. The findings thus obtained may provide useful insights into the pathogeneses of both schizophrenia and tuberculosis from the angle of cytokines. PMID- 26286215 TI - Recent Progresses in Studying Helix-Helix Interactions in Proteins by Incorporating the Wenxiang Diagram into the NMR Spectroscopy. AB - All residues in an alpha helix can be characterized and dispositioned on a 2D the wenxiang diagram, which possesses the following features: (1) the relative locations of the amino acids in the alpha-helix can be clearly displayed regardless how long it is; (2) direction of an alphahelix can be indicated; and (3) more information regarding each of the constituent amino acid residues in an alpha helix. Owing to its intuitionism and easy visibility, wenxiang diagrams have had an immense influence on our understanding of protein structure, protein protein interactions, and the effect of helical structural stability on protein conformational transitions. In this review, we summarize two recent applications of wenxiang diagrams incorporating NMR spectroscopy in the researches of the coiled-coil protein interactions related to the regulation of contraction or relaxation states of vascular smooth muscle cells, and the effects of alpha helical stability on the protein misfolding in prion disease, in hopes that the gained valuable information through these studies can stimulate more and more widely applications of wenxiang diagrams in structural biology. PMID- 26286216 TI - Light to moderate intake of alcohol, drinking patterns, and risk of cancer: results from two prospective US cohort studies. AB - OBJECTIVES: To quantify risk of overall cancer across all levels of alcohol consumption among women and men separately, with a focus on light to moderate drinking and never smokers; and assess the influence of drinking patterns on overall cancer risk. DESIGN: Two prospective cohort studies. SETTING: Health professionals in the United States. PARTICIPANTS: 88,084 women and 47,881 men participating in the Nurses' Health Study (from 1980) and Health Professionals Follow-up Study (from 1986), followed until 2010. MAIN OUTCOMES AND MEASURES: Relative risks of cancer. RESULTS: 19,269 and 7571 (excluding non-advanced prostate cancers) incident cancers were documented among women and men, respectively, over 3,144,853 person years. Compared with non-drinkers, light to moderate drinkers had relative risks of total cancer of 1.02 (95% confidence interval 0.98 to 1.06) and 1.04 (1.00 to 1.09; P(trend) = 0.12) for alcohol intake of 0.1-4.9 and 5-14.9 g/day among women, respectively. Corresponding values for men were 1.03 (0.96 to 1.11), 1.05 (0.97 to 1.12), and 1.06 (0.98 to 1.15; P(trend) = 0.31) for alcohol intake of 0.1-4.9, 5-14.9, and 15-29.9 g/day, respectively. Associations for light to moderate drinking and total cancer were similar among ever or never smokers, although alcohol consumption above moderate levels (in particular >= 30 g/day) was more strongly associated with risk of total cancer among ever smokers than never smokers. For a priori defined alcohol related cancers in men, risk was not appreciably increased for light and moderate drinkers who never smoked (P(trend) = 0.18). However, for women, even an alcohol consumption of 5-14.9 g/day was associated with increased risk of alcohol related cancer (relative risk 1.13 (95% confidence interval 1.06 to 1.20)), driven by breast cancer. More frequent and heavy episodic drinking was not further associated with risk of total cancer after adjusting for total alcohol intake. CONCLUSION: Light to moderate drinking is associated with minimally increased risk of overall cancer. For men who have never smoked, risk of alcohol related cancers is not appreciably increased for light and moderate drinking (up to two drinks per day). However, for women who have never smoked, risk of alcohol related cancers (mainly breast cancer) increases even within the range of up to one alcoholic drink a day. PMID- 26286217 TI - Light or moderate drinking is linked to alcohol related cancers, including breast cancer. PMID- 26286218 TI - Fistulizing Epstein-Barr virus-positive plasmablastic lymphoma in an HIV-positive man. AB - Plasmablastic lymphoma (PBL) is an unusual subtype of non-Hodgkin lymphoma recently classified as a diffuse immunoblastic lymphoma with a plasma-cell immunophenotype. Originally described in the oral cavity of HIV-positive patients, it has also been recognized to occur rarely at other sites. We describe a previously unreported fistulizing presentation of Epstein-Barr virus (EBV) positive PBL, reviewing its association with HIV-1 infection and its importance as an AIDS-defining malignancy. PMID- 26286219 TI - Oncologic safety of facial artery myomucosal flaps in oral cavity reconstruction. AB - BACKGROUND: Buccinator myomucosal flaps are routinely used for oral cavity reconstruction and are indicated mainly in patients classified as having stage N0 cancer. This purpose of this study was to investigate whether preservation of the vascular pedicle of the flap (facial artery and vein) during stadiative neck dissection alters the oncologic safety in these patients. METHODS: Fifty patients underwent resection of T1 to 3, N0 squamous cell carcinoma of the tongue or floor of the mouth, stadiative neck dissection, and reconstruction with a facial artery musculomucosal (FAMM) flap were retrospectively analyzed concerning rate of occult neck metastasis and recurrences. RESULTS: Occult metastasis was detected in 10 patients. Mean follow-up was 41 months. The overall survival rate was 88%, and the disease-specific survival rate was 92%. CONCLUSION: Neck dissection with preservation of the facial artery and vein does not alter the rate of regional recurrences, confirming the oncologic safety of myomucosal flaps in oral cavity reconstruction. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1200-E1202, 2016. PMID- 26286220 TI - Changes in the distribution of mechanically dependent plants along a gradient of past hurricane impact. AB - The severity of the effects that large disturbance events such as hurricanes can have on the forest canopy and the associated mechanically dependent plant community (epiphytes, climbers, etc.) is dependent on the frequency and intensity of the disturbance events. Here we investigate the effects of different structural and environmental properties of the host trees and previously modelled past hurricanes on dependent plants in Cusuco National Park, Honduras. Tree climbing methods were employed to sample different dependent life-forms in ten 150 * 150 m plots. We identified 7094 individuals of dependent plants from 214 different species. For holo- and hemi-epiphytes, we found that diversity was significantly negatively related to past hurricane impact. The abundance of dependent plants was greatly influenced by their position in tree canopy and hurricane disturbance regimes. The relationship between abundance and mean branch height shifts across a gradient of hurricane impact (from negative to positive), which might result from a combination of changes in abundance of individual species and composition of the dependent flora across sites. Mechanically dependent plants also responded to different structural and environmental conditions along individual branches. The variables that explained much of the community differences of life-forms and families among branches were branch surface area and bryophyte cover. The factors that explained most variation at a plot level were mean vapour pressure deficit and elevation. At the level of the individual tree, the most important factors were canopy openness and past hurricane impact. We believe that more emphasis needs to be placed on the effects that past disturbance events have on mechanically dependent plant communities, particularly in areas that are prone to catastrophic perturbations. PMID- 26286221 TI - Orchid-pollinator interactions and potential vulnerability to biological invasion. AB - Mutualistic relationships between plants and their pollinators have played a major role in the evolution of biodiversity. While the vulnerability of these relationships to environmental change is a major concern, studies often lack a framework for predicting impacts from emerging threats (e.g. biological invasions). The objective of this study was to determine the reliance of Platanthera ciliaris (orange-fringed orchid) on Papilio palamedes (Palamedes swallowtail butterfly) for pollination and the relative availability of alternative pollinators. Recent declines of P. palamedes larval host plants due to laurel wilt disease (LWD) could endanger P. ciliaris populations that rely heavily on this butterfly for pollination. We monitored pollinator visitation and fruit set and measured nectar spur lengths of P. ciliaris flowers and proboscis lengths of its floral visitors in Jackson County, MS, USA. Papilio palamedes was the primary visitor with minimal visitation by Phoebis sennae (cloudless sulfur butterfly). Lengths of P. ciliaris nectar spurs were similar to proboscis lengths of both pollinator species. Fruit set was moderate with access to pollinators (55 +/- 10.8 %), yet failed (0 %) when pollinators were excluded. Visitation increased with inflorescence size, but there was no such pattern in fruit set, indicating that fruit set was not limited by pollinator visitation within the range of visitation rates we observed. Our results are supported by historical data that suggest P. palamedes and P. sennae are important pollinators of P. ciliaris. Although P. sennae may provide supplemental pollination service, this is likely constrained by habitat preferences that do not always overlap with those of P. cilaris. Observed declines of P. palamedes due to LWD could severely limit the reproductive success and persistence of P. ciliaris and similar orchid species populations. This empirical-based prediction is among the first to document exotic forest pests and pathogens as an indirect threat to plant pollinator interactions. PMID- 26286223 TI - Patterns in floral traits and plant breeding systems on Southern Ocean Islands. AB - The harsh climatic conditions and paucity of potential pollinators on Southern Ocean Islands (SOIs; latitude 46 degrees S-55 degrees S) lead to the expectation that anemophily or self-fertilization are the dominant modes of plant sexual reproduction. However, at least some species have showy inflorescences suggesting biotic pollination or dimorphic breeding systems necessitating cross-pollination. This study investigates whether anemophily and self-compatibility are common on SOIs, whether species or genera with these traits are more widespread or frequent at higher latitudes, and whether gender dimorphy is correlated with anemophily, as might occur if reliance on pollinators was a disadvantage. Of the 321 flowering plant species in the SOI region, 34.3 % possessed floral traits consistent with anemophily. Compatibility information was located for 94 potentially self-fertilizing species, of which 92.6 % were recorded as partially or fully self-compatible. Dioecy occurred in 7.1 % of species overall and up to 10.2 % of island floras, but has not clearly arisen in situ. Gynodioecy occurred in 3.4 % of species. The frequency of anemophily and gender dimorphy did not differ between the SOI flora and southern hemisphere temperate reference floras. At the species level, gender dimorphy was positively associated with fleshy fruit, but at the genus level it was associated with occurrence in New Zealand and a reduced regional distribution. Anemophily was more prevalent in genera occurring on subantarctic islands and the proportion of species with floral traits suggestive of biotic pollination was significantly higher on climatically milder, cool temperate islands. These results support the contention that reliance on biotic pollinators has constrained the distribution of species on SOIs; however, it is also clear that the reproductive biology of few SOI species has been studied in situ and many species likely employ a mixed mating strategy combining biotic pollination with self-fertilization. PMID- 26286222 TI - Contrasting responses of root morphology and root-exuded organic acids to low phosphorus availability in three important food crops with divergent root traits. AB - Phosphorus (P) is an important element for crop productivity and is widely applied in fertilizers. Most P fertilizers applied to land are sorbed onto soil particles, so research on improving plant uptake of less easily available P is important. In the current study, we investigated the responses in root morphology and root-exuded organic acids (OAs) to low available P (1 MUM P) and sufficient P (50 MUM P) in barley, canola and micropropagated seedlings of potato-three important food crops with divergent root traits, using a hydroponic plant growth system. We hypothesized that the dicots canola and tuber-producing potato and the monocot barley would respond differently under various P availabilities. WinRHIZO and liquid chromatography triple quadrupole mass spectrometry results suggested that under low P availability, canola developed longer roots and exhibited the fastest root exudation rate for citric acid. Barley showed a reduction in root length and root surface area and an increase in root-exuded malic acid under low P conditions. Potato exuded relatively small amounts of OAs under low P, while there was a marked increase in root tips. Based on the results, we conclude that different crops show divergent morphological and physiological responses to low P availability, having evolved specific traits of root morphology and root exudation that enhance their P-uptake capacity under low-P conditions. These results could underpin future efforts to improve P uptake of the three crops that are of importance for future sustainable crop production. PMID- 26286224 TI - Facultative apomixis and development of fruit in a deciduous shrub with medicinal and nutritional uses. AB - Knowledge of reproductive biology of plants is crucial to understand their natural mode of propagation, which may aid in conservation and crop improvement. The reproductive details are also crucial for beginning the cultivation of a potential crop on a commercial scale. Fruits of sea buckthorn, Hippophae rhamnoides, are used in a variety of medicinal and nutritional products. So far, fruits are collected from the female plants in the wild. It is known that the species fruits profusely and also propagates by forming root suckers, but the details of sexual reproduction are not available. We investigated the mode of reproduction and development of fruits from natural populations of sea buckthorn. Megasporogenesis and megagametogenesis were studied through resin-embedded sectioning and ovule-clearing methods, and fruit development through histochemistry. The study of mitosis and male meiosis showed that the plants at the site were diploid (2n = 2x = 24). The embryo sac may develop either through the monosporic pathway and differentiates into 'Polygonum type' or aposporously into 'Panicum type'. The embryo may develop by sexual and adventitious pathways. Thus, sea buckthorn is a facultative apomict. The occurrence of diverse reproductive pathways assures the possibility of generation of novel genotypes through sexuality, while apomictic reproduction maintains adaptive genotypes and ensures reproduction in the absence of pollination. Anatomical details suggest that the fruit of sea buckthorn may be appropriately described as a pseudo-drupe. PMID- 26286225 TI - Natural populations of Arabidopsis thaliana differ in seedling responses to high temperature stress. AB - Little is known about adaptive within-species variation in thermotolerance in wild plants despite its likely role in both functional adaptation at range limits and in predicting response to climate change. Heat shock protein Hsp101, rapidly heat induced in Arabidopsis thaliana, plays a central role in thermotolerance in laboratory studies, yet little is known about variation in its expression in natural populations. We explored variation in thermotolerance and Hsp101 expression in seedlings from 16 natural populations of A. thaliana sampled along an elevation and climate gradient. We tested both naive controls (maintained at 22 degrees C until heat stress) and thermally pre-acclimated plants (exposed to a 38 degrees C 3-h acclimation treatment). After acclimation, seedlings were exposed to one of two heat stresses: 42 or 45 degrees C. Thermotolerance was measured as post-stress seedling survival and root growth. When stressed at 45 degrees C, both thermotolerance and Hsp101 expression were significantly increased by pre-acclimation. However, thermotolerance did not differ between pre acclimation and control when followed by a 42 degrees C stress. Immediately after heat stress, pre-acclimated seedlings contained significantly more Hsp101 than control seedlings. At 45 degrees C, Hsp101 expression was positively associated with survival (r(2) = 0.37) and post-stress root growth (r(2) = 0.15). Importantly, seedling survival, post-stress root growth at 45 degrees C and Hsp101 expression at 42 degrees C were significantly correlated with the home sites' first principal component of climate variation. This climate gradient mainly reflects a temperature and precipitation gradient. Thus, the extent of Hsp101 expression modulation and thermotolerance appear to be interrelated and to evolve adaptively in natural populations of A. thaliana. PMID- 26286226 TI - Your ticket to independence: a guide to getting your first principal investigator position. AB - The transition to scientific independence as a principal investigator (PI) can seem like a daunting and mysterious process to postdocs and students - something that many aspire to while at the same time wondering how to achieve this goal and what being a PI really entails. The FENS Kavli Network of Excellence (FKNE) is a group of young faculty who have recently completed this step in various fields of neuroscience across Europe. In a series of opinion pieces from FKNE scholars, we aim to demystify this process and to offer the next generation of up-and-coming PIs some advice and personal perspectives on the transition to independence, starting here with guidance on how to get hired to your first PI position. Rather than providing an exhaustive overview of all facets of the hiring process, we focus on a few key aspects that we have learned to appreciate in the quest for our own labs: What makes a research programme exciting and successful? How can you identify great places to apply to and make sure your application stands out? What are the key objectives for the job talk and the interview? How do you negotiate your position? And finally, how do you decide on a host institute that lets you develop both scientifically and personally in your new role as head of a lab? PMID- 26286227 TI - Posttraumatic Growth Outcomes and Their Correlates Among Young Adult Survivors of Childhood Cancer. AB - OBJECTIVE: This study aims to identify and examine posttraumatic growth (PTG) experiences, and their correlates, among young adult survivors of childhood cancer. METHODS: 602 long-term childhood cancer survivors between the ages of 18 and 39 participated. Their demographic (age, gender, race/ethnicity, education, relationship status, employment, and income), cancer-related (diagnosis, current health problem, age at diagnosis, and years since diagnosis), and psychosocial (social support and optimism) PTG correlates were examined using descriptive, correlational, and regression analyses. RESULTS: PTG was significantly greater for females and nonwhite survivors, and for those diagnosed at older ages. Survivors diagnosed with solid/soft tissue tumors reported lower PTG. Optimism and social support were positively associated with PTG. CONCLUSION: Study findings highlight potential intervention opportunities for increasing PTG by facilitating discussion around growth experiences within an optimistic framework among a supportive network of family members and peers. PMID- 26286228 TI - Effect of Testosterone Administration and Spiking on Reproductive Success of Broiler Breeder Flocks. AB - Age negatively affects reproductive success of broiler breeder flocks. One of the main hormones involved in the change of fertility with the age is testosterone (TT). The introduction of young males at later production stages of broiler flocks is known as spiking and is expected to reduce the fertility decline with age. The aim of this study was to determine the effect of injection of different levels of TT and the effect of spiking on reproductive fitness of broiler breeder flocks. Two experiments were conducted on Ross 308 breeder flocks for 10 weeks (41-50 weeks of age). The experiment 1 included a control and three treatments corresponding to three doses of TT (0.1, 0.2 and 0.3 cc), while the experiment 2 included a control and one treatment corresponding to spiking. The lower dose of TT (0.1 cc) and the spiking clearly slowed down the decline in hatchability. Therefore, either the external administration of TT to the males when the natural concentration of TT starts to decline or spiking the breeder flock with young roosters could contribute to improve reproductive success in later stages of the production cycle in broiler breeder flocks. PMID- 26286229 TI - Unconventional superconductivity in Y5Rh6Sn18 probed by muon spin relaxation. AB - Conventional superconductors are robust diamagnets that expel magnetic fields through the Meissner effect. It would therefore be unexpected if a superconducting ground state would support spontaneous magnetics fields. Such broken time-reversal symmetry states have been suggested for the high-temperature superconductors, but their identification remains experimentally controversial. We present magnetization, heat capacity, zero field and transverse field muon spin relaxation experiments on the recently discovered caged type superconductor Y5Rh6Sn18 ( TC= 3.0 K). The electronic heat capacity of Y5Rh6Sn18 shows a T(3) dependence below Tc indicating an anisotropic superconducting gap with a point node. This result is in sharp contrast to that observed in the isostructural Lu5Rh6Sn18 which is a strong coupling s-wave superconductor. The temperature dependence of the deduced superfluid in density Y5Rh6Sn18 is consistent with a BCS s-wave gap function, while the zero-field muon spin relaxation measurements strongly evidences unconventional superconductivity through a spontaneous appearance of an internal magnetic field below the superconducting transition temperature, signifying that the superconducting state is categorized by the broken time-reversal symmetry. PMID- 26286230 TI - Host Plant Associations and Parasitism of South Ecuadorian Eois Species (Lepidoptera: Geometridae) Feeding on Peperomia (Piperaceae). AB - The very species-rich tropical moth genus Eois Hubner (Lepidoptera: Geometridae) is a promising model group for studying host plant specialization and adaptive radiation. While most Eois species are assumed to be specialized herbivores on Piper L. species, records on other plant taxa such as Peperomia Ruiz & Pavon (Piperaceae) are still relatively scarce. Moreover, little is known about life history traits of most species, and only a few caterpillars have been described so far. We collected caterpillars associated with Peperomia (Piperaceae) host plants from June 2012 to January 2013 in three elevational bands of montane and elfin rainforests on the eastern slopes of the Andes in southern Ecuador. Caterpillars were systematically searched and reared to the adult stage. We were able to delimitate ten species of Eois on Peperomia by comparison of larval and adult morphology and by using 658 bp fragments of the mitochondrial COI gene (barcode sequences). Three of these species, Eois albosignata (Dognin), Eois bolana (Dognin), and Eois chasca (Dognin), are validly described whereas the other seven taxa represent interim morphospecies, recognized unequivocally by their DNA barcodes, and their larval and adult morphology. We provide information about their host plants, degree of parasitism, and describe the larval stages in their last instar. Additionally, caterpillars and moths are illustrated in color plates. This is the first comparative study dealing with Eois moths whose caterpillars feed on Peperomia hosts. PMID- 26286231 TI - DNA Quantity and Quality in Remnants of Traffic-Killed Specimens of an Endangered Longhorn Beetle: A Comparison of Different Methods. AB - The sampling of living insects should be avoided in highly endangered species when the sampling would further increase the risk of population extinction. Nonlethal sampling (wing clips or leg removals) can be an alternative to obtain DNA of individuals for population genetic studies. However, nonlethal sampling may not be possible for all insect species. We examined whether remnants of traffic-killed specimens of the endangered and protected flightless longhorn beetle Iberodorcadion fuliginator (L., 1758) can be used as a resource for population genetic analyses. Using insect fragments of traffic-killed specimens collected over 15 yr, we determined the most efficient DNA extraction method in relation to the state of the specimens (crushed, fragment, or intact), preservation (dried, airtight, or in ethanol), storage duration, and weight of the sample by assessing the quantity and quality of genomic DNA. A modified cetyltrimethyl ammonium bromide method provided the highest recovery rate of genomic DNA and the largest yield and highest quality of DNA. We further used traffic-killed specimens to evaluate two DNA amplification techniques (quantitative polymerase chain reaction [qPCR] and microsatellites). Both qPCR and microsatellites revealed successful DNA amplification in all degraded specimens or beetle fragments examined. However, relative qPCR concentration and peak height of microsatellites were affected by the state of specimen and storage duration but not by specimen weight. Our investigation demonstrates that degraded remnants of traffic-killed beetle specimens can serve as a source of high-quality genomic DNA, which allows to address conservation genetic issues. PMID- 26286232 TI - Low-level regulatory T-cell activity is essential for functional type-2 effector immunity to expel gastrointestinal helminths. AB - Helminth infection is frequently associated with the expansion of regulatory T cells (Tregs) and suppression of immune responses to bystander antigens. We show that infection of mice with the chronic gastrointestinal helminth Heligmosomoides polygyrus drives rapid polyclonal expansion of Foxp3(+)Helios(+)CD4(+) thymic (t)Tregs in the lamina propria and mesenteric lymph nodes while Foxp3(+)Helios( )CD4(+) peripheral (p)Treg expand more slowly. Notably, in partially resistant BALB/c mice parasite survival positively correlates with Foxp3(+)Helios(+)CD4(+) tTreg numbers. Boosting of Foxp3(+)Helios(+)CD4(+) tTreg populations by administration of recombinant interleukin-2 (rIL-2):anti-IL-2 (IL-2C) complex increased worm persistence by diminishing type-2 responsiveness in vivo, including suppression of alternatively activated macrophage and granulomatous responses at the sites of infection. IL-2C also increased innate lymphoid cell (ILC) numbers, indicating that Treg functions dominate over ILC effects in this setting. Surprisingly, complete removal of Tregs in transgenic Foxp3-DTR mice also resulted in increased worm burdens, with "immunological chaos" evident in high levels of the pro-inflammatory cytokines IL-6 and interferon-gamma. In contrast, worm clearance could be induced by anti-CD25 antibody-mediated partial depletion of early Treg, alongside increased T helper type 2 responses and without incurring pathology. These findings highlight the overarching importance of the early Treg response to infection and the non-linear association between inflammation and the prevailing Treg frequency. PMID- 26286234 TI - Somersault of Paramecium in extremely confined environments. AB - We investigate various swimming modes of Paramecium in geometric confinements and a non-swimming self-bending behavior like a somersault, which is quite different from the previously reported behaviors. We observe that Paramecia execute directional sinusoidal trajectories in thick fluid films, whereas Paramecia meander around a localized region and execute frequent turns due to collisions with adjacent walls in thin fluid films. When Paramecia are further constrained in rectangular channels narrower than the length of the cell body, a fraction of meandering Paramecia buckle their body by pushing on the channel walls. The bucking (self-bending) of the cell body allows the Paramecium to reorient its anterior end and explore a completely new direction in extremely confined spaces. Using force deflection method, we quantify the Young's modulus of the cell and estimate the swimming and bending powers exerted by Paramecium. The analysis shows that Paramecia can utilize a fraction of its swimming power to execute the self-bending maneuver within the confined channel and no extra power may be required for this new kind of self-bending behavior. This investigation sheds light on how micro-organisms can use the flexibility of the body to actively navigate within confined spaces. PMID- 26286235 TI - National survey of the management of Diabetic Ketoacidosis (DKA) in the UK in 2014. AB - AIM: To examine, in a national survey, the outcomes of adult patients presenting with DKA in 2014, mapped against accepted UK national guidance. METHODS: Data were collected in a standardized form covering clinical and biochemical outcomes, risk and discharge planning. The form was sent to all UK diabetes specialist teams (n = 220). Anonymized data were collected on five consecutive patients admitted with DKA between 1 May 2014 and 30 November 2014. RESULTS: A total of 283 forms were received (n = 281 patients) from 72 hospitals, of which 71.4% used the national guidelines. The results showed that 7.8% of cases occurred in existing inpatients, 6.1% of admissions were newly diagnosed diabetes and 33.7% of patients had had at least one episode of DKA in the preceding year. The median times to starting 0.9% sodium chloride and intravenous insulin were 41.5 and 60 min, respectively. The median time to resolution was 18.7 h and the median length of hospital stay was 2.6 days. Significant adverse biochemical outcomes occurred, with 27.6% of patients developing hypoglycaemia and 55% reported as having hypokalaemia. There were also significant issues with care processes. Initial nurse-led observations were carried out well, but subsequent patient monitoring remained suboptimal. Most patients were not seen by a member of the diabetes specialist team during the first 6 h, but 95% were seen before discharge. A significant minority of discharge letters to primary care did not contain necessary information. CONCLUSION: Despite widespread adoption of national guidance, several areas of management of DKA are suboptimal, being associated with avoidable biochemical and clinical risk. PMID- 26286236 TI - Vervets revisited: A quantitative analysis of alarm call structure and context specificity. AB - The alarm calls of vervet monkeys (Chlorocebus pygerythrus) constitute the classic textbook example of semantic communication in nonhuman animals, as vervet monkeys give acoustically distinct calls to different predators and these calls elicit appropriate responses in conspecifics. They also give similar sounding calls in aggressive contexts, however. Despite the central role the vervet alarm calls have played for understanding the evolution of communication, a comprehensive, quantitative analysis of the acoustic structure of these calls was lacking. We used 2-step cluster analysis to identify objective call types and discriminant function analysis to assess context specificity. Alarm calls given in response to leopards, eagles, and snakes could be well distinguished, while the inclusion of calls given in aggressive contexts yielded some overlap, specifically between female calls given to snakes, eagles and during aggression, as well as between male vervet barks (additionally recorded in South Africa) in leopard and aggressive contexts. We suggest that both cognitive appraisal of the situation and internal state contribute to the variation in call usage and structure. While the semantic properties of vervet alarm calls bear little resemblance to human words, the existing acoustic variation, possibly together with additional contextual information, allows listeners to select appropriate responses. PMID- 26286233 TI - IL-21 and probiotic therapy improve Th17 frequencies, microbial translocation, and microbiome in ARV-treated, SIV-infected macaques. AB - Increased mortality in antiretroviral (ARV)-treated, HIV-infected individuals has been attributed to persistent immune dysfunction, in part due to abnormalities at the gastrointestinal barrier. In particular, the poor reconstitution of gastrointestinal Th17 cells correlates with residual translocation of dysbiotic, immunostimulatory microflora across a compromised intestinal epithelial barrier. We have previously demonstrated that oral probiotics promote increased intestinal CD4(+) T-cell reconstitution during ARV treatment in a non-human primate model of HIV infection; however, essential mucosal T-cell subsets, such as Th17 cells, had limited recovery. Here, we sought to promote Th17 cell recovery by administering interleukin (IL)-21 to a limited number of ARV-treated, probiotic-supplemented, Simian Immunodeficiency Virus (SIV)-infected pigtailed macaques. We demonstrate that probiotic and IL-21 supplementation of ARVs are associated with enhanced polyfunctional Th17 expansion and reduced markers of microbial translocation and dysbiosis as compared with infected controls receiving ARVs alone. Importantly, treatment resulted in fewer morbidities compared with controls, and was independent of increased immune activation or loss of viral suppression. We propose that combining ARVs with therapeutics aimed at restoring intestinal stasis may significantly improve disease prognosis of ARV-treated, HIV-infected individuals. PMID- 26286237 TI - Three Colon Adenocarcinomas Arising in a Patient with Serrated Polyposis Syndrome: Case Report and Review of the Literature. AB - BACKGROUND: Serrated polyposis syndrome (SPS) is a rare entity mainly concerning the 6th decade of life and which is characterized by the presence of multiple large hyperplastic polyps, sessile serrated adenomas, and adenomas within the colon. CASE REPORT: We describe the case of a SPS patient with 3 synchronous adenocarcinomas. The morphologic features of serrated colorectal lesions, their characteristic molecular alterations, and their role in colorectal cancer development are discussed herein. CONCLUSION: Our findings suggest that SPS is a rare condition with an increased risk for colon cancer. Patients suffering from SPS should have regular colonoscopic surveillance, and perhaps those with numerous dysplastic hyperplastic polyps should be treated with colectomy. PMID- 26286238 TI - RHCE*cE94G encodes variable expression of c (RH4). PMID- 26286239 TI - New data on vitamin D deficiency and mortality. PMID- 26286240 TI - VATS lobectomy, history, indication, contraindication and general techniques. AB - VATS lobectomy is a respected modality of anatomic lung resections nowadays. Video-assisted lobectomies without rib extractor fulfil all current requirements for minimally invasive lung resections. This type of an anatomic pulmonary resection with a targeted treatment of hilar structures doesn't traumatize the intercostal space by using rib retractor. Videothoracoscope serves to visualize the surgical field on the screen. Assisted VATS (aVATS) lobectomy is a procedure using 3-5 cm working incision. Fully endoscopic resection (VTS) or complete VATS lobectomy (cVATS) are operations performed only through ports, without working incision. The authors supplement the article with a videorecord of VATS lobectomy general technique (Fig. 4, Ref. 11). PMID- 26286241 TI - Impact of kidney transplantation on restless legs syndrome. AB - AIM: Our study was to assess the impact of kidney transplantation on restless legs syndrome (RLS) in end stage renal disease (ESRD) patients. METHODS: A total of 75 patients after a successful kidney transplantation (39 males, 36 females) were assessed consecutively. All patients completed the self reported questionnaire focused on RLS 6 months after kidney transplantation with investigation of selected laboratory parameters. The questionnaire met the International Restless Legs Syndrome Study Group criteria for RLS diagnosis. RESULTS: 30 (40.54%) out of 75 patients met the RLS diagnostic criteria. From this RLS positive group, 8 (26.7%) of them reported a complete regression of symptoms, 13 (43.3%) reported symptoms relief, 6 (20.0%) were without any change and 3 (10.0%) reported worsening of symptoms after kidney transplantation. In the RLS positive group, the majority of patients (26-86.7%) reported the occurrence of the symptoms in the evening and 21 (70.0%) of RLS positive patients reported the onset of symptoms after the onset of renal disease. CONCLUSION: Although the secondary RLS in EDRS patients is very common, it is often unrecognized or misdiagnosed. We concluded that kidney transplantation, except the primary benefit to kidney replacement and to its function, has a secondary impact on other conditions such as RLS (Tab. 5, Fig. 4, Ref. 17). PMID- 26286242 TI - Geriatric giants--contemporary occurrence in 12,210 in-patients. AB - OBJECTIVES: With advancing age, the degree of dependency and occurrence of great geriatric syndromes (GS), also referred to as geriatric giants, grow substantially. DESIGN: The prospective cohort study was aimed at conducting an analysis and comparison of geriatric syndromes (geriatric giants) among different age groups at admission to the acute geriatric department. SETTING, PARTICIPANTS: Between 1995 and 2012, we had altogether 12,210 elderly patients at an average age of 80.5 +/- 7.0 y (range 65-103 y) hospitalised at the Department of Geriatrics. We divided the patient set into three different age subgroups (65-74 y; 75-84 y and >=85 y; e.g. 21.4%; 47.9% and 30.7%) and compared the results among them. RESULTS: 3,787 persons (31.0%) were without any GS. The growing tendency of the occurrence of all geriatric syndromes in combinations with increased age (p<0.001) is obvious. Their occurrence in the above mentioned different age sets was examined in relation to individual geriatric syndromes and sex (female and male), namely falls 22.0%, 27.8%, 39.9% and 20.5%, 27.0%, 36.1%; immobility 26.4%, 29.3%, 42.5% and 30.3%, 30.1% and 39.2%; incontinence 38.4%, 50.6%, 69.5% and 38.2%, 47.4%, 61.8 %; dementia and cognitive impairment 13.4%, 23.4%, 38.1% and 15.8%, 24.3%, 33.2% respectively. Age cut-off for geriatric syndromes occurrence based on ROC analysis is 83.5-84.5 y for females and 78.5 82.5 y for males. CONCLUSION: The occurrence of geriatric giants increasing with age and female gender is of crucial importance not only for individuals and families but also for demands on costs of health and social care in oncoming decades (Tab. 6, Fig. 3, Ref. 52). PMID- 26286243 TI - Impact of asphyxia on red blood cell folate concentration levels in newborns. AB - OBJECTIVES: To determine whether red blood cell (RBC) folate concentration levels are correlated with the occurrence of neonatal asphyxia and to study the effects of gestational age, gender, and mode of delivery on RBC folate concentration levels in newborns. BACKGROUND: Asphyxia is one of the frequent causes of morbidity and mortality of newborns. Severe perinatal asphyxia can arise due to many factors. METHODS: In a prospective study, the RBC folate concentrations were determined on day 1 of life in the whole group (n=181) of full-term (n=121) and preterm (n=60) newborns. Immunochemical analysis for the determination of folate in erythrocytes was performed. RESULTS: RBC folate concentration levels in asphyxiated newborns (n=16) were significantly decreased (median 974 ng/ml; p=0.023) in comparison with healthy newborns. On the other hand, the RBC folate concentration levels were significantly increased in preterm newborns (median 1,212 ng/ml; p=0.01) in comparison with full-term newborns (median 1,098 ng/ml). Higher RBC folate concentration levels were found in newborns which had been delivered by Caesarean section (median 1,188 ng/ml; p=0.02) compared to those born vaginally (median 1,098 ng/ml). CONCLUSION: Our results confirmed a significant decrease in RBC folate concentration in asphyxiated newborns on their first day of life (Fig. 4, Ref. 36). PMID- 26286244 TI - Laparoscopic sleeve gastrectomy for morbid obesity with natural orifice specimen extraction (NOSE). AB - OBJECTIVE: An experience with laparoscopic sleeve gastrectomy using the natural orifice specimen extraction (NOSE) technique. BACKGROUND: Bariatric surgery is nowadays the only long term effective obesity treatment method. METHODS: Twenty one consecutive patients underwent laparoscopic sleeve gastrectomy with the use of natural orifice specimen extraction (NOSE) in the Surgical Clinic of Faculty Hospital Ostrava between May 2012 and August 2012. Inclusion criteria were the body mass index (BMI) higher than 35 kg/m2 or higher than 32 kg/m2 accompanied with relevant comorbidities. RESULTS: Among 21 patients in this series, there were three men (14.3%) and 18 women (85.7%). Their mean age was 40.9+/-10.2 years. Their mean preoperative BMI was 40.4+/-4.6 kg/m2. No patient had previous bariatric surgery, one patient had laparoscopic fundoplication. All operations were completed laparoscopically with no conversions to an open procedure. In two cases, laparoscopic cholecystectomy was performed and the gallbladder was extracted along with the gastric specimen by transgastric approach. CONCLUSION: Laparoscopic sleeve gastrectomy is a safe and effective bariatric procedure with low morbidity and mortality. Based on our initial experiences it could be an indication for NOSE with transgastric approach. Obese patients would benefit from this approach due to the elimination of wound complications (Tab. 2, Fig. 3, Ref. 22). PMID- 26286245 TI - Non-linear Poincare analysis of respiratory efforts in sleep apnea. AB - OBJECTIVES: Obstructive sleep apnea (OSA) is a risk factor for hypertension, has effects on cardiovascular system and increases the sympathetic activity. The aim of the study was to evaluate the effectiveness of the non-linear Poincare plot analysis to predict OSA based on polysomnography (PSG). METHODS: The database of this study was collected by the sleep laboratory at the Philipps University in Marburg, Germany. It includes 24 PSG of men and women between 27-63 years old with obstructive and mixed sleep apnea. The start and end of apnea events in PSGs were marked. The Poincare plots of pre-apneic phase including 4-1 minutes before apnea were evaluated. Wilcoxon test was used for statistical analysis. RESULTS: Poincare analysis showed that the dynamics of chest and respiratory efforts changed two minutes before the apnea and SD1/SD2 ratios of these parameters significantly increased in the pre-apneic phase (p<=0.01). The SD1/SD2 ratio of nasal airflow did not show significant difference even in episodes close to apnea. CONCLUSIONS: Our results suggest that Poincare plot parameters of PSG have the potential to be considered predictors of apnea with the ability to show the dynamic of changes, which could lead to pre-diagnosis or prediction of apnea about 2-3 minutes before its occurrence (Tab. 2, Fig. 4, Ref. 23). PMID- 26286246 TI - Effect of coenzyme Q10 on organ damage in sepsis. AB - OBJECTIVE: Investigating the effects of coenzyme Q10 on organ damage and survival on mice in cecal ligation perforation (CLP) model in sepsis. BACKGROUND: Coenzyme Q10 is an antioxidant molecule playing an important role in mitochondria. Mitochondrial dysfunction is an important mechanism in sepsis pathophysiology. METHODS: Nintyfour Swiss Albino male mice were divided into 8 groups. CLP was performed in Group I. Coenzyme Q10, 100 mg/kg subcutaneously, was given 5 hours after CLP to Group II and 20 hours after CLP to Group III. Sham operation was performed in Group IV, 100 mg/kg coenzyme Q10 subcutaneously was given 5 hours after sham operation to Group V and 20 hours after sham operation to Group VI. No operation was performed in Group VII; coenzyme Q10, 100 mg/kg subcutaneously, was given to Group VIII. Antibiotics and fluid replacement were applied for 3 days. The mice still living were sacrificed at 576th hour. The organ damages were scored under light microscopy. RESULTS: The survival of Group I and Group II was lower than that of the control groups, but the survival in the Group III was similar to control groups. It was established that spleen, kidney, heart damage and total organ damage were decreased when compared to CLP group. CONCLUSIONS: Coenzyme Q10 is effective in decreasing histological organ damage in sepsis (Tab. 3. Fig. 1, Ref. 30). PMID- 26286247 TI - Does tamoxifen citrate prevent pulmonary fibrosis due to silica inhalation? AB - BACKGROUND: As shown in several studies, besides being used in breast cancer, tamoxifen is also known for its antifibrotic effects via reducing the serum TGF beta levels. We investigated the possible preventive effect of tamoxifen in rats exposed to silica particles depending on the antifibrotic effect. MATERIALS AND METHODS: A total of 102 adult female Wistar Albino rats were divided into five groups. First two groups (control and tmx) were free of silica and the last three groups (slc, tmx1 and tmx 10) were exposed to crystalline silica. The rats in tmx, tmx1 and tmx10 groups received 10 mg/kg, 1 mg/kg and 10 mg/kg of body weight tamoxifen, respectively. On day 84, all rats were sacrified and tissue samples were obtained together with blood samples. The differences in serum TGF-beta levels, histological grades of fibrosis and inflammation in the lung and liver tissues together with addional biochemical markers were calculated between the groups. RESULTS: Silicosis occurred in slc, tmx1 and tmx10 groups in 100%, 91.7% and 52.1%, respectively. Liver fibrosis did not occur. The highest mean lung fibrosis scores were obtained in slc group while the scores were lower in tmx1 group and the lowest in tmx10 within silica-exposed rats. Nevertheless, the inflammation scores were higher in tamoxifen-administered rats in a dose dependent pattern. CONCLUSION: Silica inhalation did not result in liver fibrosis. Tamoxifen is found to prevent lung fibrosis and reduce serum TGFbeta-1 levels while increasing lung inflammation (Tab. 3, Fig. 3, Ref. 27). PMID- 26286248 TI - Research of inhibition of survivin in rat HSC-T6 cell by siRNA interference. AB - OBJECTIVE: To explore the effects and mechanisms of siRNA targeting survivin of inducing apoptosis in rat HSC-T6 cells. METHODS: The experiment was divided into blank group, pGPU6/GFP/Neo-shNC group and pGPU6/GFP/Neo-siRNA group. The siRNA was transfected into HSC-T6 cells mediated by LipofectamineTM2000 for 24 h, and then the efficiency of transfection was observed by fluorescence microscopy. After transfection for 48h, the expression of survivin mRNA and protein was assessed by reverse transcription-polymerase chain reaction (RT-PCR) method and Western-blot, and the form of cells was observed by microscopy. The apoptosis rate of HSC-T6 cells was measured by the flow cytometry with PI staining. The expression of caspase-3 protein was assessed by western-blot. RESULTS: The prominent apoptosis of the pGPU6/GFP/Neo-siRNA group by PI staining was high, there was significant difference comparing with blank group and pGPU6/GFP/Neo- shNC group (p<0.05). The expression of caspase-3 by Western-blot in pGPU6/GFP/Neo siRNA group was high, there was significant difference comparing with blank group and pGPU6/GFP/Neo-shNC group (p>0.05). CONCLUSION: siRNA targeting survivin can inhibit the expression of survivin mRNA and protein in rat HSC-T6 cells. Expression of survivin is negative correlation with expression of caspase-3. siRNA targeting survivin may up-regulate expression of caspase-3 and increase apoptosis of rat HST-T6 (Fig. 6, Ref. 24). PMID- 26286249 TI - Protective effect of distillated Nerium oleander on heart of type 2 diabetic rats. AB - OBJECTIVES: The current study aims to investigate the possible role of NO distillate either for therapeutic or for protective potential in diabetic cardiomyopathy. BACKGROUND: Protective and restorative effects of distillated Nerium oleander (NO) on the diabetes-induced electrophysiological and structural alterations were investigated. METHODS: Type 2 diabetes was induced by combination of single dose streptozotocin injection and high fat diet for four weeks. Experimental groups were designed as follows: control, diabetic, restorative-NO treated diabetic and protective-NO treated diabetic. Intracellular action potentials (AP) and contractile activities were measured form left ventricular papillary muscle strips as well as histopathological examination of heart tissue and biochemical examinations of serum were performed. RESULTS: Type 2 diabetes induced AP prolongation was prevented with both ways of NO treatments. Moreover, treatments produced nearly complete restorations of diabetes-induced depressed amplitude and altered kinetics of contractile activities. In parallel to electrophysiological parameters, both histopathological and biochemical results indicates the NO induced beneficial effects on the diabetes related alterations. CONCLUSION: Distillated Nerium oleander (NO) can be a highly potential therapeutic or preventive agent on the diabetes induced excitation contraction coupling alterations (Tab. 3, Fig. 3, Ref. 23). PMID- 26286250 TI - Taming of Modulation Instability by Spatio-Temporal Modulation of the Potential. AB - Spontaneous pattern formation in a variety of spatially extended nonlinear systems always occurs through a modulation instability, sometimes called Turing instability: the homogeneous state of the system becomes unstable with respect to growing modulation modes. Therefore, the manipulation of the modulation instability is of primary importance in controlling and manipulating the character of spatial patterns initiated by that instability. We show that a spatio-temporal periodic modulation of the potential of spatially extended systems results in a modification of its pattern forming instability. Depending on the modulation character the instability can be partially suppressed, can change its spectrum (for instance the long wave instability can transform into short wave instability), can split into two, or can be completely eliminated. The latter result is of special practical interest, as it can be used to stabilize the intrinsically unstable system. The result bears general character, as it is shown here on a universal model of the Complex Ginzburg-Landau equation in one and two spatial dimensions (and time). The physical mechanism of the instability suppression can be applied to a variety of intrinsically unstable dissipative systems, like self-focusing lasers, reaction-diffusion systems, as well as in unstable conservative systems, like attractive Bose Einstein condensates. PMID- 26286251 TI - Co-occurrence of hypertrophic cardiomyopathy and myeloproliferative disorder in a neonate with Noonan syndrome carrying Thr73Ile mutation in PTPN11. AB - Most cases of Noonan syndrome (NS) result from mutations in one of the RAS-MAPK signaling genes, including PTPN11, SOS1, KRAS, NRAS, RAF1, BRAF, SHOC2, MEK1 (MAP2K1), and CBL. Cardiovascular diseases of varying severity, such as pulmonary stenosis and hypertrophic cardiomyopathy (HCM), are common in NS patients. RAF1 mutations are most frequent in NS with HCM, while PTPN11 mutations are also well known. Thr73Ile is a gain-of-function mutation of PTPN11, which has been highly associated with juvenile myelomonocytic leukemia and NS/myeloproliferative disease (MPD), but has not previously been reported in HCM. Here, we report a Japanese female infant with NS carrying the PTPN11 T73I mutation with NS/MPD, complete atrio-ventricular septal defect, and rapidly progressive HCM. No other HCM-related mutations were detected in PTPN11, RAF1, KRAS, BRAF, and SHOC2. This patient provides additional information regarding the genotype-phenotype correlation for PTPN11 T73I mutation in NS. PMID- 26286252 TI - Immunization with Single Oral Dose of Alginate-Encapsulated BCG Elicits Effective and Long-Lasting Mucosal Immune Responses. AB - Effective vaccination against pathogens, which enter the body through mucosal surfaces, requires the induction of both mucosal and systemic immune responses. Here, mucosal as well as systemic immune responses in the lung and spleen of BALB/c mice which were orally vaccinated with a single dose of alginate encapsulated bacille Calmette-Guerin (BCG) were evaluated. Twenty weeks after immunization, the vaccinated mice were challenged intranasally with BCG. Twelve weeks after immunization and 5 weeks after challenge, the immune responses were evaluated. Moreover, immune responses were compared with those of mice that were vaccinated with free BCG by subcutaneous (sc) and oral routes. Twelve weeks after the immunization, serum IgG level was higher in the sc-immunized mice, while serum IgA level was higher in the orally immunized mice with encapsulated BCG. Significant productions of both IgG and IgA were only detected in lungs of mice orally immunized with encapsulated BCG. Proliferative and delayed-type hypersensitivity responses and IFN-gamma production were significantly higher in mice immunized orally with encapsulated BCG, compared to mice immunized orally with free BCG. After challenge, the levels of IFN-gamma were comparable between sc-immunized mice with free BCG and orally immunized with encapsulated BCG; however, significantly less IL-4 was detected in mice which had received encapsulated BCG via oral route. Moreover, significant control of the bacilli growth in the lung of the immunized mice after intranasal challenge with BCG was documented in mice vaccinated with encapsulated BCG. These results suggest that oral immunization with alginate-encapsulated BCG is an effective mean of inducing mucosal and systemic specific immune responses. PMID- 26286253 TI - Experience with the transparotid approach via a mini-preauricular incision for surgical management of condylar neck fractures. AB - INTRODUCTION: The aim of this study was to describe our experiences of a mini preauricular transparotid approach for direct reduction and plating of condylar neck fractures. MATERIALS AND METHODS: A retrospective study was conducted on 58 patients from 2009 to 2011 with 69 condylar neck fractures in Chang Gung Memorial Hospital. The fractures were treated surgically either with a 2-cm mini preauricular and transparotid approach in 29 patients with 36 fractures, or via endoscope-assisted intraoral, or facelift or retromandibular approaches in a control group of 29 patients with 32 fractures. The postoperative hospital stay, occlusion status, mouth opening and facial nerve and parotid gland related complications were compared between the two groups. RESULTS: In both groups around 90% of patients had good restoration of preinjury occlusion. Postoperative mouth opening was 39.8 mm and 39.9 mm in the mini-preauricular approach and the other approaches group, respectively. Facial symmetry was achieved in all of the patients. There was no incidence of facial nerve palsy, infection or hemorrhage in the mini-preauricular group. One patient in the control group had a persistent weakness due to frontal nerve palsy. CONCLUSION: Based on the results, the mini preauricular approach can be an alternative, safe and effective method in the management of condylar neck and high subcondylar fractures. PMID- 26286254 TI - Echocardiographic assessment of prosthetic valves. AB - Echocardiographic evaluation of prosthetic valves is similar in many respects to evaluation of native valve disease. However, there are some important differences. First, there are several types of prosthetic valves with different fluid dynamics for each basic design and differing flow velocities for each valve size. Second, the mechanisms of valve dysfunction are somewhat different from those for native valve disease. Third, the technical aspects of imaging artificial devices, specifically the problem of acoustic shadowing, significantly affect the diagnostic approach when prosthetic valve dysfunction is suspected. Fourth, transcatheter aortic valve implantation (TAVI) has rapidly expanded in recent years. Echocardiography plays an essential role in identifying patients suitable for TAVI and providing intra-procedural monitoring, and is the modality for post-procedure follow-up. Both an understanding of the basic approach to echocardiographic evaluation and detailed knowledge of the specific flow dynamics for the size and type of prosthesis in an individual patient are needed for appropriate patient management. PMID- 26286256 TI - Knee arthrodesis using a unilateral external fixator combined with crossed cannulated screws for the treatment of end-stage tuberculosis of the knee. AB - BACKGROUND: The treatment of end-stage tuberculosis (TB) of the knee remains a significant clinical challenge, and clinical data are lacking. This study aimed to retrospectively determine the outcome of single-stage knee arthrodesis with a unilateral external fixator combined with cannulated screws for the treatment of end-stage TB. METHODS: Twenty-six patients with end-stage knee TB were treated by single-stage arthrodesis. All patients underwent open debridement and the insertion of a unilateral external fixator combined with crossed cannulated screws and received systemic antitubercular therapy. Clinical evaluations and radiographic analyses were performed after an average follow-up duration of 5.5 years. RESULTS: The mean time to radiographic bone fusion was 5.6 months. Primary full union was achieved in 25 patients (96.2%) within 8 months, and the remaining patients achieved bone fusion at 14 months postoperatively. The mean post operative alignment was 5.4 degrees valgus and 12.5 degrees flexion. The mean leg-length discrepancy was 2.8 cm. The mean VAS score improved from 67.3 before surgery to 16.2 at the last follow-up (P < 0.01), and the mean WOMAC score improved from 58.8 to 13.7 (P < 0.01). The erythrocyte sedimentation rate (ESR) and C-reactive protein level returned to normal in 25 patients by 3 months postoperatively. No recurrence in the target knee was noted. CONCLUSIONS: Single stage arthrodesis with a unilateral external fixator combined with cannulated screws can be regarded as efficacious for the treatment of end-stage knee TB. Additional studies are necessary to confirm the findings of our study. PMID- 26286255 TI - Early salpingectomy (TUbectomy) with delayed oophorectomy to improve quality of life as alternative for risk-reducing salpingo-oophorectomy in BRCA1/2 mutation carriers (TUBA study): a prospective non-randomised multicentre study. AB - BACKGROUND: Risk-reducing salpingo-oophorectomy (RRSO) around the age of 40 is currently recommended to BRCA1/2 mutation carriers. This procedure decreases the elevated ovarian cancer risk by 80-96% but it initiates premature menopause as well. The latter is associated with short-term and long-term morbidity, potentially affecting quality of life (QoL). Based on recent insights into the Fallopian tube as possible site of origin of serous ovarian carcinomas, an alternative preventive strategy has been put forward: early risk-reducing salpingectomy (RRS) and delayed oophorectomy (RRO). However, efficacy and safety of this alternative strategy have to be investigated. METHODS: A multicentre non randomised trial in 11 Dutch centres for hereditary cancer will be conducted. Eligible patients are premenopausal BRCA1/2 mutation carriers after completing childbearing without (a history of) ovarian carcinoma. Participants choose between standard RRSO at age 35-40 (BRCA1) or 40-45 (BRCA2) and the alternative strategy (RRS upon completion of childbearing and RRO at age 40-45 (BRCA1) or 45 50 (BRCA2)). Women who opt for RRS but do not want to postpone RRO beyond the currently recommended age are included as well. Primary outcome measure is menopause-related QoL. Secondary outcome measures are ovarian/breast cancer incidence, surgery-related morbidity, histopathology, cardiovascular risk factors and diseases, and cost-effectiveness. Mixed model data analysis will be performed. DISCUSSION: The exact role of the Fallopian tube in ovarian carcinogenesis is still unclear. It is not expected that further fundamental research will elucidate this role in the near future. Therefore, this clinical trial is essential to investigate RRS with delayed RRO as alternative risk reducing strategy in order to improve QoL. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02321228 ). PMID- 26286258 TI - Transcatheter tricuspid valve repair in a patient with isolated functional tricuspid valve regurgitation. PMID- 26286259 TI - Twiddler's syndrome: a rare cause of implantable cardioverter defibrillator malfunction. PMID- 26286257 TI - Successful Organizational Strategies to Sustain Use of A-CHESS: A Mobile Intervention for Individuals With Alcohol Use Disorders. AB - BACKGROUND: Mobile health (mHealth) services are growing in importance in health care research with the advancement of wireless networks, tablets, and mobile phone technologies. These technologies offer a wide range of applications that cover the spectrum of health care delivery. Although preliminary experiments in mHealth demonstrate promising results, more robust real-world evidence is needed for widespread adoption and sustainment of these technologies. OBJECTIVE: Our aim was to identify the problems/challenges associated with sustained use of an mHealth addiction recovery support app and to determine strategies used by agencies that successfully sustained client use of A-CHESS. METHODS: Qualitative inquiry assessed staff perceptions about organizational attributes and strategies associated with sustained use of the mobile app, A-CHESS. A total of 73 interviews of clinicians and administrators were conducted. The initial interviews (n=36) occurred at the implementation of A-CHESS. Follow-up interviews (n=37) occurred approximately 12 and 24 months later. A coding scheme was developed and Multiuser NVivo was used to manage and analyze the blinded interview data. RESULTS: Successful strategies used by treatment providers to sustain A-CHESS included (1) strong leadership support, (2) use of client feedback reports to follow up on non-engaged clients, (3) identify passionate staff and incorporate A-CHESS discussions in weekly meetings, (4) develop A-CHESS guidelines related to client use, (5) establish internal work groups to engage clients, and (6) establish a financial strategy to sustain A-CHESS use. The study also identified attributes of A-CHESS that enhanced as well as inhibited its sustainability. CONCLUSIONS: Mobile apps can play an important role in health care delivery. However, providers will need to develop strategies for engaging both staff and patients in ongoing use of the apps. They will also need to rework business processes to accommodate the changes in communication frequency and style, learn to use app data for decision making, and identify financing mechanisms for supporting these changes. PMID- 26286260 TI - Left ventricular pseudoaneurysm after transapical aortic valve-in-valve implantation: use of transthoracic 3D echocardiography for guiding therapeutic approach. PMID- 26286261 TI - A 45-year-old woman with chest pain after coronary stenting. PMID- 26286262 TI - Erratum to: Acaricidal effect and histological damage induced by Bacillus thuringiensis protein extracts on the mite Psoroptes cuniculi. PMID- 26286263 TI - Early results from a multi-component French public-private partnership initiative to improve participation in clinical research - CeNGEPS: a prospective before after study. AB - BACKGROUND: A public-private (51/49 %) partnership was initiated in 2007 in France to improve the attractiveness of French sites in industry-sponsored international clinical trials. This initiative developed and implemented a combination of structuring actions and support actions. Here we report the assessment of the impact after 6 years on participation of French study sites in industry-sponsored clinical trials. METHODS: We performed a prospective before after study of clinical research activities in French public hospitals to assess the impact of actions developed and implemented by CeNGEPS. The programme involved a combination of structuring actions (establishment of sites of excellence, national networks and dedicated clinical research assistants (CRAs)), support actions (tools, templates and training) and competitive budget allocation for sites or networks based on performance. The impact was assessed using the following performance criteria: 1) reduction of the delay to contract signature to <= 60 days for 80 % of the trial sites; 2) inclusion of >=80 % of the planned number of patients by at least 80 % of trial sites; 3) closure of <15 % of trials sites without patients enrolled. RESULTS: In 2013, the median delay to contract signature was: 55 days, compared with 76 days in 2008 (27.6 % reduction), 50.5 % of all sites and 58 % of sites with a dedicated CRA included >=80 % of the planned number of patients compared with 44.8 % in 2008 (12.7 % increase) and 21.3 % of all sites and 9 % of sites with a dedicated CRA closed with no patients included, compared with 26.4 % in 2008 (19.3 and 65.9 %, respectively). CONCLUSIONS: These results provide evidence that it is possible to improve a country's attractiveness for industry-sponsored clinical research. The two main actions, i.e. establishing sites of excellence throughout the country with well trained, dedicated staff and establishing a national network of clinical investigators, could be adapted to other countries in Western Europe to improve Europe's attractiveness to industry-funded trials. PMID- 26286264 TI - Meningitis and Reversible Cerebral Vasoconstriction Syndrome During the Postpartum Period. PMID- 26286265 TI - Heterogeneity of primary outcome measures used in clinical trials of treatments for intermediate, posterior, and panuveitis. AB - BACKGROUND: Uveitis describes a heterogeneous group of conditions characterized by intraocular inflammation. Since most of the sight-threatening forms of uveitis are individually rare, there has been an increasing tendency for clinical trials to group distinct uveitis syndromes together despite clear variations in phenotype which may reflect real aetiological and pathogenetic differences. Furthermore this grouping of distinct syndromes, and the range of manifestations within each uveitis syndrome, leads to a wide range of possible outcome measures. In this study we wished to review the degree of consensus or otherwise in the choice of primary outcome measures for registered clinical trials related to uveitis. METHODS: Systematic review of data provided in clinical trial registries describing clinical trials dealing with medical treatment of intermediate, posterior, or panuveitis through 01 October 2013. We reviewed 15 on-line clinical trial registries approved by the International Committee of Medical Journal Editors. We identified all that met the following inclusion criteria: prospective, interventional design; target populations with intermediate, posterior or panuveitis; and one or more pre-specified outcome measures that were related to uveitis. Primary outcome measures were classified in terms of type (efficacy or safety or both; single, composite, or multiple); dimension (disease activity, disease damage, measured or patient-reported visual function); and domain (the specific study variable being measured). RESULTS: Of 195 registered uveitis studies, we identified 104 clinical trials that met inclusion criteria. There were 14 different domains used as primary outcome measures. Among clinical trials that utilized primary outcome measures of treatment efficacy (n = 94), 70 (74 %) used a measure of disease activity (vitreous haze in 40/70 [57 %]; macular oedema in 19/70 [27 %]) and 49 (70 %) used a measure of visual function (visual acuity in all cases). Multiple primary outcome measures were used in 23 (22 %) of 104 clinical trials. With regard to quality, in 12 (12 %) of 104 clinical trials, outcome measures were poorly defined. No clinical trial utilized a patient reported study variable as primary outcome measure. CONCLUSIONS: This systematic review highlights the heterogeneity of outcome measures used in recent clinical trials for intermediate, posterior, and panuveitis. Current designs prioritize clinician-observed measures of disease activity and measurement of visual function as outcome measures. This apparent lack of consensus regarding outcome measures for the study of uveitis is a concern, as it prevents comparison of studies and meta-analyses, and weakens the evidence available to stake-holders, from patients to clinicians to regulators, regarding the efficacy and value of a given treatment. PMID- 26286266 TI - Impact of extrusion processing conditions on lipid peroxidation and storage stability of full-fat flaxseed meal. AB - BACKGROUND: The full-fat flaxseed (Linum usitatissimum L.) meal has obtained relatively new flourished concept as food or feedstuff for the development of healthier products. It provides favorable balance of polyunsaturated, monounsaturated and saturated fatty acids. However, flaxseed meal may be susceptible to oxidation by exposure to various storage conditions which is extremely undesirable and produces toxic compounds to human health. Another consideration in the application of flaxseed meal relates to the presence of anti nutritional compounds that need to be minimized using appropriate processing method. The present research work was conducted to evaluate the impact of extrusion processing conditions and storage of full-fat flaxseed meal on functional characteristics such as alpha-linolenic acid content, lipid peroxidation and sensory attributes. METHODS: The raw flaxseed meal was analyzed for cyanogenic glycosides, tannin and mucilage anti-nutritional compounds. Fatty acids composition was quantified by gas chromatography. The meal was extruded at barrel exit temperature (100-140 degrees C), screw speed (50-150 rpm), feed rate (30-90 kg/h) and feed moisture (10-30 %) for reduction of anti-nutritional compounds. The raw and extruded meals were stored for a ninety-day period under room conditions (20-25 degrees C). Lipid peroxidation was analyzed by peroxide, free fatty acids, conjugated dienes, total volatiles and malondialdehyde assay. Color, aroma and overall acceptability attributes were evaluated by sensory multiple comparison tests. RESULTS: The raw flaxseed meal possessed significant amount of anti-nutritional compounds, lipid and alpha-linolenic acid contents. The extrusion processing at high barrel exit temperature (140 degrees C) significantly reduced the cyanogenic compounds (84 %), tannin (73 %) and mucilage (27 %) in the flaxseed meal. The alpha-linolenic acid content and lipid peroxidation did not significantly change after extrusion processing or during storage at the end of 60 days. Fluctuations in sensory attributes occurred during storage, but at the end of 90 days, only the extruded samples presented negative effect and showed lowest consumer acceptability. CONCLUSIONS: The present study suggested that extrusion of flaxseed meal at optimum conditions and stored for 60 days did not change the stability of full-fat flaxseed meal and can be used as supplement or ingredient for the production of various healthier products. PMID- 26286267 TI - Immobilization of trypsin in organic and aqueous media for enzymatic peptide synthesis and hydrolysis reactions. AB - BACKGROUND: Immobilization of enzymes onto different carriers increases enzyme's stability and reusability within biotechnological and pharmaceutical applications. However, some immobilization techniques are associated with loss of enzymatic specificity and/or activity. Possible reasons for this loss are mass transport limitations or structural changes. For this reason an immobilization method must be selected depending on immobilisate's demands. In this work different immobilization media were compared towards the synthetic and hydrolytic activities of immobilized trypsin as model enzyme on magnetic micro-particles. RESULTS: Porcine trypsin immobilization was carried out in organic and aqueous media with magnetic microparticles. The immobilization conditions in organic solvent were optimized for a peptide synthesis reaction. The highest carrier activity was achieved at 1 % of water (v/v) in dioxane. The resulting immobilizate could be used over ten cycles with activity retention of 90 % in peptide synthesis reaction in 80 % (v/v) ethanol and in hydrolysis reaction with activity retention of 87 % in buffered aqueous solution. Further, the optimized method was applied in peptide synthesis and hydrolysis reactions in comparison to an aqueous immobilization method varying the protein input. The dioxane immobilization method showed a higher activity coupling yield by factor 2 in peptide synthesis with a maximum activity coupling yield of 19.2 % compared to aqueous immobilization. The hydrolysis activity coupling yield displayed a maximum value of 20.4 % in dioxane immobilization method while the aqueous method achieved a maximum value of 38.5 %. Comparing the specific activity yields of the tested immobilization methods revealed maximum values of 5.2 % and 100 % in peptide synthesis and 33.3 % and 87.5 % in hydrolysis reaction for the dioxane and aqueous method, respectively. CONCLUSIONS: By immobilizing trypsin in dioxane, a beneficial effect on the synthetic trypsin activity resilience compared to aqueous immobilization medium was shown. The results indicate a substantial potential of the micro-aqueous organic protease immobilization method for preservation of enzymatic activity during enzyme coupling step. These results may be of substantial interest for enzymatic peptide synthesis reactions at mild conditions with high selectivity in industrial drug production. PMID- 26286268 TI - Quantitative analysis of pathogens in the lower respiratory tract of patients with chronic obstructive pulmonary disease. AB - BACKGROUND: Bacterial infection of the lower respiratory tract is believed to play a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and acute exacerbations of COPD (AECOPD). This study investigates the potential relationship between AECOPD and the load of six common bacterial pathogens in the lower respiratory tract using real-time quantitative PCR (RT qPCR) in COPD patients. METHODS: Protected specimen brush (PSB) and bronchoalveolar lavage fluid (BALF) samples from the lower respiratory tract of 66 COPD patients and 33 healthy subjects were collected by bronchoscopy. The load of Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Pseudomonos aeruginosa, Haemophilus influenzeae, and Moraxella catarrhalis were detected by RT-qPCR. RESULTS: High Klebsiella pneumoniae, Pseudomonos aeruginosa, Haemophilus influenzeae and Moraxella catarrhalis burden were detected by RT-qPCR in both PSB and BALF samples obtained from stable COPD and AECOPD patients compared with healthy subjects. The load of the above four pathogenic strains in PSB and BALF samples obtained from AECOPD patients were significantly higher compared with stable COPD patients. Finally, positive correlations between bacterial loads and inflammatory mediators such as neutrophil count and cytokine levels of IL-1beta, IL-6 and IL-8, as well as negative correlations between bacterial loads and the forced expiratory volume in one second (FEV1) % predicted, forced vital capacity (FVC) % predicted, and FEV1/FVC ratio, were detected. CONCLUSIONS: These findings suggest that increased bacterial loads mediated inflammatory response in the lower respiratory tract and were associated with AECOPD. In addition, these results provide guidance for antibiotic therapy of AECOPD patients. PMID- 26286269 TI - End stage renal disease caused by thromboangiitis obliterans: a case report. AB - INTRODUCTION: Thromboangiitis obliterans or Buerger's disease is a nonatherosclerotic, segmental, inflammatory vasculitis that is strongly associated with tobacco products and commonly affects the small- and medium-sized arteries of the upper and lower extremities. However, the disease can, rarely, involve large central or visceral arteries. We report here the case of end stage renal disease due to renal artery thrombosis caused by thromboangiitis obliterans. CASE PRESENTATION: A 51-year-old Korean man who had previously required amputation of both great toes due to thromboangiitis obliterans presented with left flank pain and oliguria. Both his renal arteries were occluded on contrast-enhanced abdominal computed tomography and abdominal angiography. He also had abdominal angina. He had no risk factor of thromboembolism from cardiac origin, atherosclerosis except for tobacco abuse, collagen diseases or hypercoagulable disorders. Renal failure and mesenteric ischemia associated with thromboangiitis obliterans progression was diagnosed. CONCLUSIONS: Renal failure due to renal artery thrombosis and mesenteric ischemia represents an unusual manifestation of thromboangiitis obliterans. But once it occurs, it can be life-threatening. When we care for a patient with thromboangiitis obliterans, we should pay attention to this rare disease course, and encourage cessation of the smoking of tobacco products. PMID- 26286270 TI - Chryseobacterium echinoideorum sp. nov., isolated from sea urchins (Tripneustes gratilla). AB - A Gram-stain-negative, aerobic, non-motile, rod-shaped, flexirubin-producing bacterium, designated strain CC-CZW010T, was isolated from the edible sea urchin Tripneustes gratilla in Penghu Island, Taiwan. The isolate grew optimally at pH 7.0 and 30 degrees C in the presence of 2 % (w/v) NaCl. The most closely related strains in terms of 16S rRNA gene sequence similarity were Chryseobacterium taihuense NBRC 108747T (97.6 %) and Chryseobacterium aquaticum KCTC 12483T (96.7 %). Phylogenetic analyses based on 16S rRNA gene sequences revealed a distinct taxonomic position attained by strain CC-CZW010T with respect to other species of the genus Chryseobacterium. Strain CC-CZW010T possessed iso-C15 : 0, anteiso-C15 : 0, iso-C17 : 0 3-OH, summed feature 3 (comprising C16 : 1omega7c/C16 : 1omega6c) and summed feature 9 (comprising C16 : 0 10-methyl/iso-C17 : 1omega9c) as predominant fatty acids. The major polar lipid profile consisted of phosphatidylethanolamine, two unidentified lipids and five aminolipids. The polyamine pattern contained the major compound sym-homospermidine. Menaquinone 6 (MK-6) was the predominant respiratory quinone, and the G+C content of the genomic DNA was 36.4 mol%. According to distinct phylogenetic, phenotypic and chemotaxonomic features, strain CC-CZW010T represents a novel species of the genus Chryseobacterium, for which the name Chryseobacterium echinoideorum sp. nov. is proposed. The type strain is CC-CZW010T ( = BCRC 80786T = JCM 30470T). PMID- 26286271 TI - Fracture resistance of three different posts in restoration of severely damaged primary anterior teeth: An in vitro study. AB - BACKGROUND: Restoration of anterior primary teeth with severe caries lesion is a big challenge. The aim of this study was to compare the fracture resistance of three types of post, including composite resin, customized quartz fiber and prefabricated glass fiber in restoration of severely damaged primary anterior teeth. MATERIALS AND METHODS: Sixty extracted human primary maxillary incisors were randomly divided into three groups: Group 1: Customized quartz fiber post, Group 2: Composite post and Group 3: Prefabricated glass fiber post. Due to the effect of bonded area on the fracture resistance, the bonded surface of each sample was measured 1 mm above cementoenamel junction. An increasing force was subjected with a crosshead speed of 0.5 mm/min by a universal testing machine until fracture occurred, and the failure mode was assessed afterwards. Data were analyzed using One-way analysis of variance and Kruskal-Wallis tests. The level of significance was considered at P < 0.05. RESULTS: The mean fracture resistance values of three groups were 343.28 N, 278.70 N and 284.76 N, respectively. Although customized quartz fiber post showed the greatest fracture resistance, statistical analysis revealed no significant difference between groups (P = 0.21). The mean fracture strength values of three groups were 12.82 N/mm(-2), 11.93 N/mm(-2) and 11.31 N/mm(-2), respectively; however, the differences were not statistically significant (P = 0.72). Favorable failure mode was more frequent in all groups (P = 0.12). CONCLUSION: Within the limitations of this study, it can be concluded that all three types of studied posts can be successfully used to restore badly destructed primary anterior teeth. PMID- 26286272 TI - The Active Phase of Palladium during Methane Oxidation. AB - The active phase of Pd during methane oxidation is a long-standing puzzle, which, if solved, could provide routes for design of improved catalysts. Here, density functional theory and in situ surface X-ray diffraction are used to identify and characterize atomic sites yielding high methane conversion. Calculations are performed for methane dissociation over a range of Pd and PdOx surfaces and reveal facile dissociation on either under-coordinated Pd sites in PdO(101) or metallic surfaces. The experiments show unambiguously that high methane conversion requires sufficiently thick PdO(101) films or metallic Pd, in full agreement with the calculations. The established link between high activity and atomic structure enables rational design of improved catalysts. PMID- 26286273 TI - Phase Separation and Molecular Intermixing in Polymer-Fullerene Bulk Heterojunction Thin Films. AB - The phase separation and molecular intermixing in poly(3-hexylthiophene) (P3HT)/[6,6]-phenyl-C61 butyric acid methyl ester (PCBM) bulk heterojunction thin films are investigated as a function of the overall PCBM content. The structural length scales, phase sizes, and molecular miscibility ratio in bulk heterojunction films are probed with grazing incidence small-angle neutron scattering (GISANS). The PCBM content is varied between 9 and 67 wt %. For the symmetric P3HT/PCBM ratio, which is typically highly efficient in photovoltaic devices, a structure size of 20 nm, the largest PCBM phases, and 18 vol % dispersed PCBM in the amorphous P3HT phase are found. The molecularly dispersed PCBM content is found to increase with the overall PCBM content. Absorption measurements complement the GISANS investigation. PMID- 26286274 TI - Mechanism and Reaction Coordinate of Directional Charge Separation in Bacterial Reaction Centers. AB - Using first-principles molecular dynamics, we predict the reaction coordinate and mechanism of the first charge-separation step in the reaction center of photosynthetic bacteria in a model including the special pair (P) and closest relevant residues. In the ground state, a dynamical localization of the highest occupied orbital is found to be a defining characteristic of P. This feature is linked to the tuning of the orbital energy levels by the coupling with two collective low-frequency vibrational modes. After electronic excitation, we demonstrate one specific mode that couples to P*, representing the reaction coordinate along which the excited state develops. The characteristic vibrational coordinate we predict to be the rotation of an axial histidine (HisM202), which selectively lowers the energy of one (PM) of the two bacteriochlorophylls in P. This leads to a unidirectional displacement of electron density to establish PL(+)PM(-) charge-transfer character, a hypothesis well-supported by an extensive framework of experimental evidence. PMID- 26286275 TI - Soret Band of the Gas-Phase Ferri-Cytochrome c. AB - We report the first visible spectrum of a heme-protein in the gas phase. The aim of this work was to provide a reference for the optical absorption of an isolated heme-protein to better understand the influence of protein conformation and fluctuation and of solvent on its optical properties. After laser irradiation of gas-phase cytochrome c (cyt c), electron emission is observed. Electron photodetachment yield of cyt c 6- was recorded in the region of the Soret band of the porphyrin group, showing a maximum at 410 nm. Our results are compared with optical spectra of gas-phase heme and of cyt c in solution. We discuss the influence of the polypeptide chain and of the solvent on both the position and the broadening of the Soret band. Action spectrum of gas-phase cyt c is close to the absorption of native cyt c in solution, suggesting an efficient protection of the heme group from solvent accessibility by the polypeptide chain and similar interactions between the two moieties in solution and the gas phase. PMID- 26286276 TI - Efficient and Robust Heteronuclear Cross-Polarization for High-Speed-Spinning Biological Solid-State NMR Spectroscopy. AB - We present a new and highly efficient approach for heteronuclear coherence transfer in solid-state NMR spectroscopy under high-speed spinning conditions. The so-called (RESPIRATION)CP experiment exploits phase-alternated recoupling on only one of the two rf channels intertwined in a synchronized train of short rf pulses on both channels. The method provides significantly higher efficiencies than state-of-the art techniques including ramped and adiabatic cross polarization experiments with long durations of intense rf irradiation. At the same time, it is easier to setup experimentally and significantly more robust toward imperfections such as rf inhomogeneity, misadjustments, and sample-induced variations in the rf tuning. The method is described analytically, numerically, and experimentally for biological solids. We demonstrate sensitivity gains of factors of 1.3 and 1.8 for typical (1)H->(15)N and (15)N->(13)C transfers and a combined gain of a factor of 2-4 for a typical NCA experiment for biological solid-state NMR. PMID- 26286277 TI - Electron Transfer Mechanism in Helical Peptides. AB - Electrochemical studies of a set of ferrocene-labeled helical peptides of increasing length were carried out by forming self-assembled monolayers (SAMs) on gold electrodes. Electron transfer (ET) rates showed a very weakly distance dependent nature that has been interpreted as a result of a dynamically controlled tunneling mechanism. Specifically, the slow equilibrium between the alpha- and the 310 helical conformers in a SAM has been invoked, and the rate of formation of the more conductive 310 conformer has been proposed to be related to the ET rates observed. PMID- 26286278 TI - Nonmonotonic Size-Dependent Carrier Mobility in PbSe Nanocrystal Arrays. AB - On the basis of a tight binding system-bath model, we investigated carrier mobility of PbSe nanocrystal (NC) arrays as a function of NC size and inter-NC separation. The size-dependent trend of calculated carrier mobilities are in excellent agreement with recent experimental measurements: electron mobility increased up to NC diameter of ~6 nm and then decreased for larger NCs, whereas hole mobility showed a monotonic size-dependency. Carrier mobility increase was associated with reduced activation energy that governs charge-transfer processes. In contrast, the decrease in electron mobility for large NCs was found to be due to smaller electronic coupling. Control of inter-NC separation is crucial for mobility enhancement: the mobility may change by an order of magnitude when inter NC separation varies by as little as 1 to 2 A. We anticipate similar size dependency of the mobility in other semiconductor NC arrays, although crossover diameter in which mobility reaches its maximum depends on the material. PMID- 26286279 TI - Single Airborne Dust Particles using Plasmonic Metal Films with Hole Arrays. AB - An airborne dust particle is trapped in the hole of a plasmonic metal film with a patterned array of holes (mesh) by pumping air through the mesh. Both scatter free infrared spectra and scanning electron images are obtained on the same individual airborne dust particle, showing the feasibility of multiple, nondestructive experiments on a single, subwavelength particle. Ultimately, this may help to elucidate the effect of shape, orientation, and crystallinity on IR dust particle spectra. PMID- 26286280 TI - Breaking Through the Glass Ceiling: Recent Experimental Approaches to Probe the Properties of Supercooled Liquids near the Glass Transition. AB - Experimental measurements of the properties of supercooled liquids at temperatures near their glass transition temperatures, Tg, are requisite for understanding the behavior of glasses and amorphous solids. Unfortunately, many supercooled molecular liquids rapidly crystallize at temperatures far above their Tg, making such measurements difficult to nearly impossible. In this Perspective, we discuss some recent alternative approaches to obtain experimental data in the temperature regime near Tg. These new approaches may yield the additional experimental data necessary to test current theoretical models of the dynamical slowdown that occurs in supercooled liquids approaching the glass transition. PMID- 26286281 TI - Anisotropic Interactions in Protein Mixtures: Self Assembly and Phase Behavior in Aqueous Solution. AB - Recent experimental studies show that oppositely charged proteins can self assemble to form seemingly stable microspheres in aqueous salt solutions. We here use parallel tempering Monte Carlo simulations to study protein phase separation of lysozyme/alpha-lactalbumin mixtures and show that anisotropic electrostatic interactions are important for driving protein self-assembly. In both dilute and concentrated protein phases, the proteins strongly align according to their charge distribution. While this alignment can be greatly diminished by a single point mutation, phase separation is completely suppressed when neglecting electrostatic anisotropy. The results highlight the importance of subtle electrostatic interactions even in crowded biomolecular environments where other short-ranged forces are often thought to dominate. PMID- 26286282 TI - Many-Body Nature of Relaxation Processes in Glass-Forming Systems. AB - Most glass-forming systems are composed of basic units interacting with each other with a nontrivial anharmonic potential. Naturally, relaxation and diffusion in glass formers is a many-body problem. Results from recent experimental studies are presented to show the effects of many-body relaxation and diffusion manifested on the dynamic properties of glass formers. Considering that the effects are general and critical, the problem of glass transition will not be solved until the many-body nature of the relaxation process has been incorporated fundamentally into any theory. PMID- 26286283 TI - Ion Transport in Liquid Salt Solutions with Oxide Dispersions: "Soggy Sand" Electrolytes. AB - "Soggy sand" electrolyte, which essentially consists of oxide dispersions in nonaqueous liquid salt solutions, comprises an important class of soft matter electrolytes. The ion transport mechanism of soggy sand electrolyte is complex. The configuration of particles in the liquid solution has been observed to depend in a nontrivial manner on various parameters related to the oxide (concentration, size, surface chemistry) and solvent (dielectric constant, viscosity) as well as time. The state of the particles in solution not only affects ionic conductivity but also effectively the mechanical and electrochemical properties of the solid liquid composite. Apart from comprehensive understanding of the underlying phenomena that govern ion transport, which will benefit design of better electrolytes, the problem has far-reaching implications in diverse fields such as catalysis, colloid chemistry, and biotechnology. PMID- 26286284 TI - Double sigma-Aromaticity in a Surface-Deposited Cluster: Pd4 on TiO2 (110). AB - We report double sigma-aromaticity in a surface-deposited cluster, Pd4, on the TiO2 (110) surface. In the gas phase, Pd4 adopts a tetrahedral structure. However, surface binding promotes a flat, sigma-aromatic cluster. This is the first time aromaticity has been found in surface-deposited clusters. The concept of aromaticity is expected to become instrumental in predicting and interpreting properties of such systems, much like it is for isolated molecules and clusters. PMID- 26286285 TI - Strength of NH...S Hydrogen Bonds in Methionine Residues Revealed by Gas-Phase IR/UV Spectroscopy. AB - Despite of being ubiquitous in proteins, NHbackbone...S hydrogen bonds linking the sulfur atom of methionine or cysteine to backbone NH groups remain poorly documented. Here, we report vibrationally resolved IR NH stretch spectra of two methionine-containing dipeptides (Ac-Phe-Met-NH2 and Ac-Met-Phe-NH2). The conformations observed for both molecules, assigned with the help of DFT-D quantum chemistry, provide spectroscopic evidence for the formation of NHbackbone...S H-bonds, surprisingly strong enough to challenge the classical intrabackbone NH...O?C H-bonds. The methionine side chain is found to fold locally, forming a H-bond with the neighboring amide groups (NH(i) or NH(i+1)). Comparison with protein data bank structural information shows that such a local folding is also common in proteins where it concerns 24% of the methionine residues that have a sulfur atom linked to a backbone NH group. This convergence between the strength of these NH...S H-bonds and protein structural data illustrates their contribution to the stability of protein chains. PMID- 26286286 TI - Simulation and Experiment - A Difficult Interaction. PMID- 26286287 TI - Emergence of Zeolite Analogs and other Microporous Crystals in an Atomic Lattice Model of Silica and Related Materials. AB - The potential of tailored nanopores to transform technologies such as drug delivery, biofuel production, and optical-electronic devices depends on fundamental knowledge of the self-assembly of ordered nanoporous solids. Atomic level geometries of critical nuclei that lead to such solids have remained hidden in the nanoscale blind spot between local (<0.5 nm) and collective (>5 nm) probes of structure. Heroic efforts at molecular simulation of nanopore formation have provided massive libraries of hypothetical structures; (1-5) however, to date no statistical simulation has generated a crystallization pathway from random initial condition to ordered nanoporous solid, until now. In this work, we show that a recently developed atomic lattice model of silica and related materials can form ordered nanoporous solids with a rich variety of structures including known chalcogenides, zeolite analogs, and layered materials. We find that whereas canonical Monte Carlo simulations of the model consistently produce the amorphous solids studied in our previous work, parallel tempering Monte Carlo gives rise to ordered nanoporous solids. The utility of parallel tempering highlights the existence of barriers between amorphous and crystalline phases of our model. Moreover, the self-assembly or nanoporous crystalline phases in the model open the door to detailed understanding of nanopore nucleation. PMID- 26286288 TI - Ultrafast Exciton Dynamics in Silicon Nanowires. AB - Ultrafast exciton dynamics in one-dimensional (1D) silicon nanowires (SiNWs) have been investigated using femtosecond transient absorption techniques. A strong transient bleach feature was observed from 500 to 770 nm following excitation at 470 nm. The bleach recovery was dominated by an extremely fast feature that can be fit to a triple exponential with time constants of 0.3, 5.4, and ~75 ps, which are independent of probe wavelength. The amplitude and lifetime of the fast component were excitation intensity-dependent, with the amplitude increasing more than linearly and the lifetime decreasing with increasing excitation intensity. The fast decay is attributed to exciton-exciton annihilation upon trap state saturation. The threshold for observing this nonlinear process is sensitive to the porosity and surface properties of the sample. To help gain insight into the relaxation pathways, a four-state kinetic model was developed to explain the main features of the experimental dynamics data. The model suggests that after initial photoexcitation, conduction band (CB) electrons become trapped in the shallow trap (ST) states within 0.5 ps and are further trapped into deep trap (DT) states within 4 ps. The DT electrons finally recombine with the hole with a time constant of ~500 ps, confirming the photophysical processes to which we assigned the decays. PMID- 26286289 TI - Plasma-Assisted Reduction of Graphene Oxide at Low Temperature and Atmospheric Pressure for Flexible Conductor Applications. AB - Reduction of graphene oxide (GO) at low temperature and atmospheric pressure via plasma-assisted chemistry is demonstrated. Hydrogen gas is continuously dissociated in a microplasma to generate atomic hydrogen, which flows from the remote plasma to thin films of GO deposited on a substrate. Direct interaction with ions and other energetic species is avoided to mitigate ion-induced sputter removal or damage. The residual oxygen content and structure of the GO films after plasma treatment is systematically characterized at different temperatures and correlated to the conductivity of the films. For example, at 150 degrees C, we find that the plasma-reduced GO contains less than 12.5% oxygen and exhibits a sheet resistance of 4.77 * 10(4) Omega/sq, as compared with thermal reduction alone, which results in 22.9% oxygen and a sheet resistance of 2.14 * 10(6) Omega/sq. Overall, the effective removal of oxygen functional groups by atomic hydrogen enables large-scale applications of GO as flexible conductors to be realized. PMID- 26286290 TI - Polarization- and Azimuth-Resolved Infrared Spectroscopy of Water on TiO2(110): Anisotropy and the Hydrogen-Bonding Network. AB - We have investigated the structure and dynamics of thin water films adsorbed on TiO2(110) using infrared reflection-absorption spectroscopy (IRAS) and ab initio molecular dynamics. Infrared spectra were obtained for s- and p-polarized light with the plane of incidence parallel to the [001] and [110] azimuths for water coverages <= 4 monolayers. The spectra indicate strong anisotropy in the water films. The vibrational densities of states predicted by the ab initio simulations for 1 and 2 monolayer coverages agree well with the observations. The results provide new insight into the structure of water on TiO2(110) and resolve a long standing puzzle regarding the hydrogen bonding between molecules in the first and second monolayers on this surface. The results also demonstrate the capabilities of polarization- and azimuth-resolved IRAS for investigating the structure and dynamics of adsorbates on dielectric substrates. PMID- 26286291 TI - Graphene Oxides as Tunable Broadband Nonlinear Optical Materials for Femtosecond Laser Pulses. AB - Graphene oxide (GO) thin films on glass and plastic substrates were found to display interesting broadband nonlinear optical properties. We have investigated their optical limiting activity for femtosecond laser pulses at 800 and 400 nm, which could be tuned by controlling the extent of reduction. The as-prepared GO films were found to exhibit excellent broadband optical limiting behaviors, which were significantly enhanced upon partial reduction by using laser irradiation or chemical reduction methods. The laser-induced reduction of GO resulted in enhancement of effective two-photon absorption coefficient at 400 nm by up to ~19 times and enhancement of effective two- and three-photon absorption coefficients at 800 nm by ~12 and ~14.5 times, respectively. The optical limiting thresholds of partially reduced GO films are much lower than those of various previously reported materials. Highly reduced GO films prepared by using the chemical method displayed strong saturable absorption behavior. PMID- 26286292 TI - Carrier Transport in Heterojunction Nanocrystals Under Strain. AB - We present a theory for carrier transport in semiconducting nanoscale heterostructures that emphasizes the effects of strain at the interface between two different crystal structures. An exactly solvable model shows that the interface region, or junction, acts as a scattering potential that facilitates charge separation. As a case study, we model a type-II CdS/ZnSe heterostructure. After advancing a theory similar to that employed in model molecular conductance calculations, we calculate the electron and hole photocurrents and conductances, including nonlinear effects, through the junction at steady state. PMID- 26286293 TI - Large Variations of the Raman Signal in the Spectra of Twisted Bilayer Graphene on a BN Substrate. AB - We report an unusual enhancement of the Raman signal of the G mode in a twisted graphene bilayer (2-LG) on a hexagonal single-crystalline boron nitride substrate. We used an isotopically engineered 2-LG, where the top layer was composed of (13)C atoms and the bottom layer of (12)C atoms. Consequently, it was possible by Raman spectroscopy to distinguish between the enhancement coming from the top and bottom layers. The enhancement of the G mode was, however, found to be similar for the top and bottom layers, and this enhancement effect was observed only at certain locations on the substrate. The experiment with two different laser excitation energies showed that the location of the enhanced spots is dependent on the laser excitation energy. Therefore our results suggest that the enhancement comes from new states in the electronic structure, which are a consequence of a local specific rotation of the grains in graphene layers. PMID- 26286295 TI - Synthesis of GO supported Fe2O3-TiO2 nanocomposites for enhanced visible-light photocatalytic applications. AB - This article reports novel ternary composites consisting of Fe2O3 nanorods, TiO2 nanoparticles, and graphene oxide (GO) flakes that provide enhanced photocatalytic performance and stability. Fe2O3 nanorods grow evenly and embed themselves on the agglomerated TiO2/GO surface, which facilitate the formation of heterojunctions for effective migration of charge carriers at the interface of Fe2O3/TiO2 in the ternary composites. The formation of heterostructured Fe2O3 TiO2/GO composites and the effect of GO addition on the photophysical properties of the composites were systematically investigated using various spectroscopic techniques. The photocatalytic performance of Fe2O3 was improved by coupling with TiO2 in the presence of GO, suggesting uncommon electron transfer from the conduction band of Fe2O3 to that of TiO2via GO under visible-light irradiation. An improved charge separation in the composite materials compared with that in bare Fe2O3 was confirmed by drastic fluorescence quenching and stronger absorption in the visible range. The optimum content of GO in the ternary composite was 1.0 wt%, which exhibited enhanced photocatalytic activity. The synergistic effect, heterostructured composite and role of GO, as an electron transporter, in the ternary composites account for the enhanced photocatalytic activity. PMID- 26286294 TI - Mitoxantrone, More than Just Another Topoisomerase II Poison. AB - Mitoxantrone is a synthetic anthracenedione originally developed to improve the therapeutic profile of the anthracyclines and is commonly applied in the treatment of breast and prostate cancers, lymphomas, and leukemias. A comprehensive overview of the drug's molecular, biochemical, and cellular pharmacology is presented here, beginning with the cardiotoxic nature of its predecessor doxorubicin and how these properties shaped the pharmacology of mitoxantrone itself. Although mitoxantrone is firmly established as a DNA topoisomerase II poison within mammalian cells, it is now clear that the drug interacts with a much broader range of biological macromolecules both covalently and noncovalently. Here, we consider each of these interactions in the context of their wider biological relevance to cancer therapy and highlight how they may be exploited to further enhance the therapeutic value of mitoxantrone. In doing so, it is now clear that mitoxantrone is more than just another topoisomerase II poison. PMID- 26286296 TI - Validation of the Sexual Communication Self-Efficacy Scale. AB - This study assessed a newly developed Sexual Communication Self-Efficacy Scale designed to measure the sexual communication self-efficacy of adolescent men and women. Three-hundred and seventy-four U.K. adolescents completed this new scale, along with several other validity measures. Factor analysis revealed that the Sexual Communication Self-Efficacy Scale consisted of five underlying factors: contraception communication, positive sexual messages, negative sexual messages, sexual history, and condom negotiation. These factors demonstrated high internal consistency and presents evidence to support construct validity. This scale may have utility in assessing the effectiveness of interventions designed to enhance sexual communication and sexual health behaviors among young people. PMID- 26286297 TI - Intraclass Correlation Coefficients for Obesity Indicators and Energy Balance Related Behaviors Among New York City Public Elementary Schools. AB - OBJECTIVE: Sample size and statistical power calculation should consider clustering effects when schools are the unit of randomization in intervention studies. The objective of the current study was to investigate how student outcomes are clustered within schools in an obesity prevention trial. METHOD: Baseline data from the Food, Health & Choices project were used. Participants were 9- to 13-year-old students enrolled in 20 New York City public schools (n= 1,387). Body mass index (BMI) was calculated based on measures of height and weight, and body fat percentage was measured with a Tanita(r) body composition analyzer (Model SC-331s). Energy balance-related behaviors were self-reported with a frequency questionnaire. To examine the cluster effects, intraclass correlation coefficients (ICCs) were calculated as school variance over total variance for outcome variables. School-level covariates, percentage students eligible for free and reduced-price lunch, percentage Black or Hispanic, and English language learners were added in the model to examine ICC changes. RESULTS: The ICCs for obesity indicators are: .026 for BMI-percentile, .031 for BMIz-score, .035 for percentage of overweight students, .037 for body fat percentage, and .041 for absolute BMI. The ICC range for the six energy balance related behaviors are .008 to .044 for fruit and vegetables, .013 to .055 for physical activity, .031 to .052 for recreational screen time, .013 to .091 for sweetened beverages, .033 to .121 for processed packaged snacks, and .020 to .083 for fast food. When school-level covariates were included in the model, ICC changes varied from -95% to 85%. CONCLUSIONS: This is the first study reporting ICCs for obesity-related anthropometric and behavioral outcomes among New York City public schools. The results of the study may aid sample size estimation for future school-based cluster randomized controlled trials in similar urban setting and population. Additionally, identifying school-level covariates that can reduce cluster effects is important when analyzing data. PMID- 26286298 TI - Increases in Network Ties Are Associated With Increased Cohesion Among Intervention Participants. AB - OBJECTIVE: Many behavior change programs are delivered in group settings to manage implementation costs and to foster support and interactions among group members in order to facilitate behavior change. Understanding the group dynamics that evolve in group settings (e.g., weight management, Alcoholics Anonymous) is important, yet rarely measured. This article examined the relationship between social network ties and group cohesion in a group-based intervention to prevent obesity in children. METHOD: The data reported are process measures from an ongoing community-based randomized controlled trial. A total of 305 parents with a child (3-6 years) at risk of developing obesity were assigned to an intervention that taught parents healthy lifestyles. Parents met weekly for 12 weeks in small consistent groups. Two measures were collected at Weeks 3 and 6: a social network survey (people in the group with whom one discusses healthy lifestyles) and the validated Perceived Cohesion Scale. We used lagged random and fixed effects regression models to analyze the data. RESULTS: Cohesion increased from 6.51 to 6.71 (t= 4.4,p< .01). Network nominations tended to increase over the 3-week period in each network. In the combined discussion and advice network, the number of nominations increased from 1.76 to 1.95 (z= 2.59,p< .01). Cohesion at Week 3 was the strongest predictor of cohesion at Week 6 (b= 0.55,p< .01). Number of new network nominations at Week 6 was positively related to cohesion at Week 6 (b= 0.06,p< .01). In sum, being able to name new network contacts was associated with feelings of cohesion. CONCLUSION: This is the first study to demonstrate how network changes affect perceived group cohesion within a behavioral intervention. Given that many behavioral interventions occur in group settings, intentionally building new social networks could be promising to augment desired outcomes. PMID- 26286299 TI - Arrhythmic risk stratification by programmed ventricular stimulation in Brugada syndrome: the end of the debate? PMID- 26286300 TI - We only find what we look for: fetal heart rate and the diagnosis of long-QT syndrome. PMID- 26286301 TI - Prophylactic implantable defibrillators for hypertrophic cardiomyopathy: disarray in the era of precision medicine. PMID- 26286302 TI - Epicardial ablation in post-myocardial infarction ventricular tachycardia: could it be one of the missing pieces of the puzzle? PMID- 26286303 TI - Misplaced brain sodium channels in heart kindle sudden death in epilepsy. PMID- 26286304 TI - Twelve-lead ECG of ventricular tachycardia in structural heart disease. PMID- 26286305 TI - Is ablation to termination the best strategy for ablation of persistent atrial fibrillation? Persistent atrial fibrillation is best ablated by a strategy that terminates the arrhythmia: procedural termination is associated with improved long-term outcomes. PMID- 26286306 TI - Is ablation to termination the best strategy for ablation of persistent atrial fibrillation? Ablation to termination is not the best strategy during ablation. PMID- 26286307 TI - Mechanism of a wide QRS complex tachycardia with variable atrial, his, and ventricular relationships. PMID- 26286308 TI - Wobble. PMID- 26286309 TI - Three-dimensional transesophageal echocardiography to facilitate transseptal puncture and left atrial appendage occlusion via upper extremity venous access. PMID- 26286310 TI - Discordant junctional beats and preexcitation: what is the mechanism? PMID- 26286311 TI - Letter from Papagiannis and Kanter regarding article, "variable clinical features and ablation of manifest nodofascicular/ventricular pathways". PMID- 26286312 TI - Response to letter regarding article, "variable clinical features and ablation of manifest nodofascicular/ventricular pathways". PMID- 26286313 TI - Letter from Patane regarding article, "atrial fibrosis and conduction slowing in the left atrial appendage of patients undergoing thoracoscopic surgical pulmonary vein isolation for atrial fibrillation". PMID- 26286315 TI - Correction. PMID- 26286314 TI - Response to letter regarding article, "atrial fibrosis and conduction slowing in the left atrial appendage of patients undergoing thoracoscopic surgical pulmonary vein isolation for atrial fibrillation". PMID- 26286316 TI - Effect of Hypoxia on DDR1 Expression in Pituitary Adenomas. AB - BACKGROUND: Pituitary adenoma is a common intracranial tumor in neurosurgery. Some pituitary adenomas have the characteristics of invasive growth make them unable to be removed completely by surgery leading to easy relapse. Discoidin domain receptor l (DDR1) is a new kind of tyrosine kinase receptor on the cell surface. DDR1 can be activated by tumor microenvironment signal in tumorigenesis, increasing MMP-2/9 expression and promoting the invasive ability of tumor cells. Anoxia can promote tumor growth and metastasis. This study investigated the impact of anoxic environment DDR1 expression in pituitary adenoma. MATERIAL AND METHODS: A primary hypoxia pituitary adenoma cell model was established and treated with DDR1 inhibitor nilotinib. Real-time PCR and Western blot were used to detect DDR1 mRNA and protein expression. ELISA was used to detect MMP-2/9 changes. MTT method was used to detect pituitary adenoma cell proliferation. We used a transwell chamber to determine pituitary adenoma cell invasion ability. RESULTS: DDR1 mRNA and protein were significantly overexpressed under hypoxia (P<0.05). MMP-2 and MMP-9 expression was obviously increased in supernatant (P<0.05). Pituitary adenoma cell proliferation and invasive ability improved markedly under hypoxia (P<0.05). Nilotinib could reduce DDR1 expression, decrease MMP-2 and MMP-9 expression, and inhibit pituitary adenoma cells proliferation and invasion. CONCLUSIONS: Hypoxia can increase DDR1 expression in pituitary adenoma cells, leading to improved MMP-2 and MMP-9 secretion, and promoting pituitary adenoma cell proliferation and invasion. PMID- 26286317 TI - An Ambient Intelligence Framework for End-User Service Provisioning in a Hospital Pharmacy: a Case Study. AB - End-user development is a new trend to provide tailored services to dynamic environments such as hospitals. These services not only facilitate daily work for pharmacy personnel but also improve self-care in elder people that are still related to hospital, such as discharged patients. This paper presents an ambient intelligence (AmI) environment for End-user service provisioning in the pharmacy department of Gregorio Maranon Hospital in Madrid, composed of a drug traceability infrastructure (DP-TraIN) and a ubiquitous application for enabling the pharmacy staff to create and execute their own services for facilitating drug management and dispensing. The authors carried out a case study with various experiments where different roles from the pharmacy department of Gregorio Maranon Hospital were involved in activities such as drug identification, dispensing and medication administering. The authors analyzed the effort required to create services by pharmacy staff, the discharged patients' perception of the AmI environment and the quantifiable benefits in reducing patient waiting time for drug dispensing. PMID- 26286318 TI - A nanofibrous polypyrrole/silicon composite derived from cellulose substance as the anode material for lithium-ion batteries. AB - A bio-inspired nanofibrous polypyrrole/silicon composite derived from natural cellulose substance was synthesized. Due to its unique porous network structure and PPy coating on the silicon fibres, it showed improved reversible capacity, cyclability and rate capability upon long-term charge/discharge cycling when employed as an anode material for lithium-ion batteries. PMID- 26286319 TI - 1H, 13C and 15N resonance assignments and secondary structure of the human PHF6 ePHD1 domain. AB - The plant homeodomain (PHD) finger 6 (PHF6) is a multidomain protein that comprises four nuclear localization signals and two extended PHD zinc finger domains (ePHD), suggesting that the PHD domains of PHF6 may have different functions compared with other PHD domains. And the PHF6 was first identified as the gene mutated associated with Borjeson-Forssman-Lehmann syndrome, an X-linked mental retardation disorder. The mutant PHF6 is also associated with T cell acute lymphoblastic leukemia and acute myeloid leukemia. But the molecular mechanism between these diseases and PHF6 are still unclear. In addition, the first conserved ePHD (ePHD1) of PHF6 is involved in its nucleolus localization, directly interacts with upstream binding factor (UBF) and suppresses rRNA transcription. Here we show the backbone resonance and side chain assignments of the PHF6-ePHD1 domain from human by heteronuclear multidimensional NMR spectroscopy and its secondary structure as predicted by the TALOS+. These assignments of PHF6-ePHD1 domain throw a light on the further structure determination, dynamics and interaction with UBF. PMID- 26286320 TI - 1H, 13C and 15N resonance assignments of a C-terminal domain of human CHD1. AB - Chromatin remodelling proteins are an essential family of eukaryotic proteins. They harness the energy from ATP hydrolysis and apply it to alter chromatin structure in order to regulate all aspects of genome biology. Chromodomain helicase DNA-binding protein 1 (CHD1) is one such remodelling protein that has specialised nucleosome organising abilities and is conserved across eukaryotes. CHD1 possesses a pair of tandem chromodomains that directly precede the core catalytic Snf2 helicase-like domain, and a C-terminal SANT-SLIDE DNA-binding domain. We have identified an additional conserved domain in the C-terminal region of CHD1. Here, we report the backbone and side chain resonance assignments for this domain from human CHD1 at pH 6.5 and 25 degrees C (BMRB No. 25638). PMID- 26286321 TI - Construct Polyoxometalate Frameworks through Covalent Bonds. AB - An emerging strategy for exploring the application of polyoxometalates (POMs) is to assemble POM clusters into open-framework materials, especially inorganic organic hybrid three-dimensional (3D) open-framework materials, via the introduction of different organic linkers between the POM clusters. This strategy has yielded a few 3D crystalline POMs of which a typical class is the group of polyoxometalate metal-organic frameworks (POMMOFs). However, for reported POMMOFs, only coordination bonds are involved between the linkers and POM clusters, and it has not yet produced any covalently bonded polyoxometalate frameworks. Here, the concept of "covalently bonded POMs (CPOMs)" is developed. By using vanadoborates as an example, we showed that the 3D CPOMs can be obtained by a condensation reaction through the oxolation mechanism of polymer chemistry. In particular, suitable single crystals were harvested and characterized by single-crystal X-ray diffraction. This work forges a link among polymer science, POM chemistry, and open-framework materials by demonstrating that it is possible to use covalent bonds according to polymer chemistry principles to construct crystalline 3D open-framework POM materials. PMID- 26286322 TI - Age and aggregation trigger mating behaviour in the small hive beetle, Aethina tumida (Nitidulidae). AB - This study aimed to investigate the poorly documented reproductive behaviour of the small hive beetle, Aethina tumida (Nitidulidae), a honey bee (Apis mellifera) parasite. We described the mating behaviour in detail and tested the hypothesis that beetle aggregation plays a vital role in mating in this species. Gender preference was examined in the context of age-dependency and possible chemical communication. Beetles started mating at a high frequency 18 days after emergence from the soil but only if they were aggregated (p < 0.001); mating was infrequent when beetles were paired. Males in aggregation also tried to copulate with males and only copulated more frequently with females at 18 days after emergence from soil (p < 0.001) in contrast to newly emerged, 7-day-old and 60-day-old beetles. Males and females spent more time in social contact with the opposite sex (p < 0.01) when they were 18 days old in contrast to 7-day-old beetles. Filter papers which had been in contact with 21-day-old beetles were highly attractive to similar-aged beetles of the opposite sex (p < 0.01). This suggests that chemical substances produced by the beetles themselves play a role in mating. Mating behaviour was characterised by a short pre-copulation courtship and female aggression towards other females and copulating couples. Both behaviours may be indicative of cryptic female choice. Delayed onset of reproductive behaviour is typical of many polygamous species, whilst the indispensability of aggregation for onset of sexual behaviour seems to be a feature unique to A. tumida. Both strategies support mass reproduction in this parasitic species, enabling A. tumida to overcome its honey bee host colony, and are probably triggered by chemotactic cues. . PMID- 26286323 TI - An experimental test for age-related improvements in reproductive performance in a frog that cares for its young. AB - Reproductive performance often increases with age in long-lived iteroparous organisms, a pattern that can result from within-individual increases in effort and/or competence. In free-living populations, it is typically difficult to distinguish these mechanisms or to isolate particular features of reproduction influencing outcomes. In captive Oophaga pumilio, a frog in which mothers provide extended offspring provisioning via trophic eggs, we experimentally manipulated the age at which females started breeding and then monitored them across repeated reproductive events. This experiment allowed us to decouple age and experience and isolate maternal care as the proximate source of any differences in performance. Younger first-time mothers produced larger broods than older first time mothers, but did not rear more offspring to independence. Across repeated reproductive events, maternal age was unassociated with any metric of performance. At later reproductive events, however, mothers produced fewer metamorphs, and a lower proportion of individuals in their broods reached independence. These patterns suggest that performance does not improve with age or breeding experience in this frog, and that eventual declines in performance are driven by reproductive activity, not age per se. Broadly, age-specific patterns of reproductive performance may depend on the proximate mechanism by which parents influence offspring fitness and how sensitive these are to effort and competence. PMID- 26286329 TI - Influencing factors on serum 25-hydroxyvitamin D3 levels in Japanese chronic hepatitis C patients. AB - BACKGROUND: Serum 25-hydroxyvitamin D3 levels are generally lower in chronic hepatitis C patients than in healthy individuals. The purpose of this study is to clarify the factors which affect serum 25-hydroxyvitamin D3 levels using data obtained from Japanese chronic hepatitis C patients. METHODS: The subjects were 619 chronic hepatitis C patients. Serum 25-hydroxyvitamin D3 levels were measured by using double-antibody radioimmunoassay between April 2009 and August 2014. Serum 25-hydroxyvitamin D3 levels of 20 ng/mL or less were classified as vitamin D deficiency, and those with serum 25-hydroxyvitamin D3 levels of 30 ng/mL or more as vitamin D sufficiency. The relationship between patient-related factors and serum 25-hydroxyvitamin D3 levels was analyzed. RESULTS: The cohort consisted of 305 females and 314 males, aged between 18 and 89 years (median, 63 years). The median serum 25-hydroxyvitamin D3 level was 21 ng/mL (range, 6-61 ng/mL). On the other hand, the median serum 25-hydroxyvitamin D3 level in the healthy subjects was 25 ng/mL (range, 7-52), being significantly higher than that those in 80 chronic hepatitis C patients matched for age, gender, and season (p = 1.16 * 10(-8)). In multivariate analysis, independent contributors to serum 25 hydroxyvitamin D3 deficiency were as follows: female gender (p = 2.03 * 10(-4), odds ratio = 2.290, 95 % confidence interval = 1.479-3.545), older age (p = 4.30 * 10(-4), odds ratio = 1.038, 95 % confidence interval = 1.017-1.060), cold season (p = 0.015, odds ratio = 1.586, 95 % confidence interval = 1.095-2.297), and low hemoglobin level (p = 0.037, odds ratio = 1.165, 95 % confidence interval = 1.009-1.345). By contrast, independent contributors to serum 25-hydroxyvitamin D3 sufficiency were male gender (p = 0.001, odds ratio = 3.400, 95 % confidence interval = 1.635-7.069), warm season (p = 0.014, odds ratio = 1.765, 95 % confidence interval = 1.117-2.789) and serum albumin (p = 0.016, OR = 2.247, 95 % CI = 1.163-4.342). CONCLUSIONS: Serum 25-hydroxyvitamin D3 levels in chronic hepatitis C Japanese patients were influenced by gender, age, hemoglobin level, albumin and the season of measurement. PMID- 26286330 TI - A method for estimating intrinsic noise in electroretinographic (ERG) signals. AB - PURPOSE: To develop a signal processing paradigm for extracting ERG responses to temporal sinusoidal modulation with contrasts ranging from below perceptual threshold to suprathreshold contrasts and estimate the magnitude of intrinsic noise in ERG signals at different stimulus contrasts. METHODS: Photopic test stimuli were generated using a 4-primary Maxwellian view optical system. The 4 primary lights were sinusoidally temporally modulated in-phase (36 Hz; 2.5-50% Michelson contrast). The stimuli were presented in 1-s epochs separated by a 1-ms blank interval and repeated 160 times (160.160-s duration) during the recording of the continuous flicker ERG from the right eye using DTL fibre electrodes. After artefact rejection, the ERG signal was extracted using Fourier transforms in each of the 1-s epochs where a stimulus was presented. The signal processing allows for computation of the intrinsic noise distribution in addition to the signal-to-noise (SNR) ratio. RESULTS: We provide the initial report that the ERG intrinsic noise distribution is independent of stimulus contrast, whereas SNR decreases linearly with decreasing contrast until the noise limit at ~2.5%. The 1 ms blank intervals between epochs de-correlated the ERG signal at the line frequency (50 Hz) and thus increased the SNR of the averaged response. We confirm that response amplitude increases linearly with stimulus contrast. The phase response shows a shallow positive relationship with stimulus contrast. CONCLUSIONS: This new technique will enable recording of intrinsic noise in ERG signals above and below perceptual visual threshold and is suitable for measurement of continuous rod and cone ERGs across a range of temporal frequencies, and post-receptoral processing in the primary retinogeniculate pathways at low stimulus contrasts. The intrinsic noise distribution may have application as a biomarker for detecting changes in disease progression or treatment efficacy. PMID- 26286324 TI - MitiiTM ABI: study protocol of a randomised controlled trial of a web-based multi modal training program for children and adolescents with an Acquired Brain Injury (ABI). AB - BACKGROUND: Acquired brain injury (ABI) refers to multiple disabilities arising from damage to the brain acquired after birth. Children with an ABI may experience physical, cognitive, social and emotional-behavioural impairments which can impact their ability to participate in activities of daily living (ADL). Recent developments in technology have led to the emergence of internet delivered therapy programs. "Move it to improve it" (MitiiTM) is a web-based multi-modal therapy that comprises upper limb (UL) and cognitive training within the context of meaningful physical activity. The proposed study aims to compare the efficacy of MitiiTM to usual care to improve ADL motor and processing skills, gross motor capacity, UL and executive functioning in a randomised waitlist controlled trial. METHODS/DESIGN: Sixty independently ambulant children (30 in each group) at least 12 months post ABI will be recruited to participate in this trial. Children will be matched in pairs at baseline and randomly allocated to receive either 20 weeks of MitiiTM training (30 min per day, six days a week, with a potential total dose of 60 h) immediately, or be waitlisted for 20 weeks. Outcomes will be assessed at baseline, immediately post-intervention and at 20 weeks post-intervention. The primary outcomes will be the Assessment of Motor and Process Skills and 30 s repetition maximum of functional strength exercises (sit to-stand, step-ups and half kneel to stand). Measures of body structure and functions, activity, participation and quality of life will assess the efficacy of MitiiTM across all domains of the International Classification of Functioning, Disability and Health framework. A subset of children will undertake three tesla (3T) magnetic resonance imaging scans to evaluate functional neurovascular changes, structural imaging, diffusion imaging and resting state functional connectivity before and after intervention. DISCUSSION: MitiiTM provides an alternative approach to deliver intensive therapy for children with an ABI in the convenience of the home environment. If MitiiTM is found to be effective, it may offer an accessible and inexpensive intervention option to increase therapy dose. TRIAL REGISTRATION: ANZCTR12613000403730. PMID- 26286332 TI - Users or Students? Privacy in University MOOCS. AB - Two terms, student privacy and Massive Open Online Courses, have received a significant amount of attention recently. Both represent interesting sites of change in entrenched structures, one educational and one legal. MOOCs represent something college courses have never been able to provide: universal access. Universities not wanting to miss the MOOC wave have started to build MOOC courses and integrate them into the university system in various ways. However, the design and scale of university MOOCs create tension for privacy laws intended to regulate information practices exercised by educational institutions. Are MOOCs part of the educational institutions these laws and policies aim to regulate? Are MOOC users students whose data are protected by aforementioned laws and policies? Many university researchers and faculty members are asked to participate as designers and instructors in MOOCs but may not know how to approach the issues proposed. While recent scholarship has addressed the disruptive nature of MOOCs, student privacy generally, and data privacy in the K-12 system, we provide an in depth description and analysis of the MOOC phenomenon and the privacy laws and policies that guide and regulate educational institutions today. We offer privacy case studies of three major MOOC providers active in the market today to reveal inconsistencies among MOOC platform and the level and type of legal uncertainty surrounding them. Finally, we provide a list of organizational questions to pose internally to navigate the uncertainty presented to university MOOC teams. PMID- 26286331 TI - The impact of a self-development coaching programme on medical and dental students' psychological health and academic performance: a randomised controlled trial. AB - BACKGROUND: Psychological distress is well-documented worldwide among medical and dental students. Few studies have assessed the impact of self-development coaching programs on the students' psychological health. The aim of the study was to evaluate the effect of a self-development coaching programme on the psychological health and academic performance of preclinical medical and dental students at Umm Al-Qura University, Saudi Arabia. METHODS: Four-hundred and twenty-two participants (n = 422, 20-22 years) fulfilled the study requirements and were invited into a parallel-randomised controlled trial that was partially blinded. Participants were stratified by faculty, gender, and academic year, and then randomised. A total of 156 students participated in the intervention group (IG) and 163 students participated in the control group (CG). The IG received the selfdevelopment programme, involving skills and strategies aimed to improve students' psychological health and academic performance, through a two-day workshop. Meanwhile, the CG attended an active placebo programme focussing on theoretical information that was delivered through a five-hour workshop. Both programmes were conducted by the same presenter during Week 1 of the second semester of the 2012-2013 academic year. Data were gathered immediately before (T1), one week after (T2) and five weeks (T3) after the intervention. Psychological health was measured using the Depression Anxiety Stress Scale (DASS 21), the General Self-Efficacy (GSE), and the Satisfaction With Life Scale (SWLS). Academic performance was measured using students' academic weighted grades (WG). Student cognitive and emotional perceptions of the intervention were measured using the Credibility/Expectancy Questionnaire (CEQ). RESULTS: Data from 317 students, who completed the follow ups, were analysed across the three time periods (IG, n = 155; CG, n = 162). The baseline variables and demographic data of the IG and CG were not significantly different. The IG showed short-term significant reductions in depression and anxiety in compared to CG from T1 to T2. The short-term changes in stress, GSE and SWLS of the IG were not significantly different from those of the CG. While both groups showed a significant change on most of the psychological variables from T1 to T3, no significant differences were found between the groups in this period. In addition, no significant difference was found in WG between the IG and CG after the intervention. No harms relevant to the intervention were reported. CONCLUSION: The investigated self development coaching programme showed only a short-term improvement on depression and anxiety compared with an active control. There was no effect of the intervention on academic performance. TRIAL REGISTRATION: ACTRN12614000896673. PMID- 26286333 TI - Evaluation of psychometric properties and differential item functioning of 8-item Child Perceptions Questionnaires using item response theory. AB - BACKGROUND: Four-factor structure of the two 8-item short forms of Child Perceptions Questionnaire CPQ11-14 (RSF:8 and ISF:8) has been confirmed. However, the sum scores are typically reported in practice as a proxy of Oral health related Quality of Life (OHRQoL), which implied a unidimensional structure. This study first assessed the unidimensionality of 8-item short forms of CPQ11-14. Item response theory (IRT) was employed to offer an alternative and complementary approach of validation and to overcome the limitations of classical test theory assumptions. METHODS: A random sample of 649 12-year-old school children in Hong Kong was analyzed. Unidimensionality of the scale was tested by confirmatory factor analysis (CFA), principle component analysis (PCA) and local dependency (LD) statistic. Graded response model was fitted to the data. Contribution of each item to the scale was assessed by item information function (IIF). Reliability of the scale was assessed by test information function (TIF). Differential item functioning (DIF) across gender was identified by Wald test and expected score functions. RESULTS: Both CPQ11-14 RSF:8 and ISF:8 did not deviate much from the unidimensionality assumption. Results from CFA indicated acceptable fit of the one-factor model. PCA indicated that the first principle component explained >30 % of the total variation with high factor loadings for both RSF:8 and ISF:8. Almost all LD statistic <10 indicated the absence of local dependency. Flat and low IIFs were observed in the oral symptoms items suggesting little contribution of information to the scale and item removal caused little practical impact. Comparing the TIFs, RSF:8 showed slightly better information than ISF:8. In addition to oral symptoms items, the item "Concerned with what other people think" demonstrated a uniform DIF (p < 0.001). The expected score functions were not much different between boys and girls. CONCLUSIONS: Items related to oral symptoms were not informative to OHRQoL and deletion of these items is suggested. The impact of DIF across gender on the overall score was minimal. CPQ11-14 RSF:8 performed slightly better than ISF:8 in measurement precision. The 6-item short forms suggested by IRT validation should be further investigated to ensure their robustness, responsiveness and discriminative performance. PMID- 26286334 TI - Acute necrotizing pneumonia combined with parapneumonic effusion caused by Mycobacterium lentiflavum: a case report. AB - BACKGROUND: Mycobacterium lentiflavum (M. lentiflavum), a slow growing nontuberculous mycobacterium (NTM), has recently been described as an emerging human pathogen regardless of the immune status of the host. Previous reports have demonstrated that cervical lymphadenitis of children is the most frequent pathology of M. lentiflavum. However, there are little reports regarding pulmonary diseases by M. lentiflavum specifically in immunocompetent patients. CASE PRESENTATION: A 60-year-old man having prolonged productive cough and dyspnea with fever was initially diagnosed as pneumonia with parapneumonic effusion. Imaging studies showed that the radiologic abnormality was acute bronchopneumonic infiltration with abscess formation in the left lower lobe and parapneumonic pleural effusion. M. lentiflavum was identified in the cultured pleural tissues. On the basis of these findings, he was diagnosed as pulmonary infection and pleurisy caused by M. lentiflavum, which was treated with a combination of antibiotics covering NTM. His clinical manifestations were dramatically improved by the treatment targeting NTM, while those were refractory to empirical antibiotic therapy. CONCLUSION: In this report, we introduce the isolation of M. lentiflavum from pleural tissues associated with acute necrotizing pneumonia combined with parapneumonic effusion in an immunocompetent host, suggesting that the M. lentiflavum can be a human pathogen invovled in pulmonary infectious diseases and pleurisy with poor response to empirical antibiotic treatment. PMID- 26286335 TI - Looking out for the blind spot. PMID- 26286336 TI - Ectopia lentis in Marfan's syndrome causing positional visual symptoms. PMID- 26286337 TI - Patient-Reported Symptoms over 48 Weeks in a Randomized, Open-Label, Phase 3b Non inferiority Trial of Adults with HIV Switching to Coformulated Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir DF Versus Continuation of Ritonavir Boosted Protease Inhibitor with Emtricitabine and Tenofovir DF. AB - BACKGROUND: Coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF; Stribild((r))) is a recommended integrase inhibitor-based regimen in treatment guidelines from the US Department of Health and Human Services and the British HIV Association. The purpose of this analysis was to determine the change in patient-reported symptoms over time among HIV infected adults who switch to Stribild((r)) versus those continuing on a protease inhibitor (PI) with FTC/TDF. METHODS: A secondary analysis was conducted on the STRATEGY-PI study (GS-US-236-0115, ClinicalTrials.gov NCT01475838), a randomized, open-label, phase 3b trial of HIV-infected adults taking a PI with FTC/TDF who were randomly assigned (2:1) either to Stribild((r)) (switch) or continuation of their existing regimen (no-switch). Logistic regressions and longitudinal modeling were conducted to evaluate the relationship of treatment with bothersome symptoms. RESULTS: At week 4 as compared with baseline, the switch group experienced a statistically significantly lower prevalence in five symptoms (diarrhea/loose bowels, bloating/pain/gas in stomach, pain/numbness/tingling in hands/feet, nervous/anxious, and trouble remembering). The lower prevalence of diarrhea/loose bowels, bloating/pain/gas in stomach, and pain/numbness/tingling in hands/feet observed at week 4 was maintained over time. While there were no significant differences between groups in the prevalence of sad/down/depressed and problems with sex at week 4 or week 48, longitudinal models indicated the switch group had a statistically significantly decreased prevalence in both symptoms from week 4 to week 48. As compared with the no-switch group, higher levels of satisfaction with treatment were experienced by patients in the switch group at the first follow-up visit and at week 24. CONCLUSIONS: In this study sample, a switch from a ritonavir-boosted PI, FTC, and TDF regimen to coformulated EVG/COBI/FTC/TDF was associated with more treatment satisfaction and a reduction in the prevalence of patient-reported diarrhea/loose bowel symptoms, which was maintained over the 48-week study period. PMID- 26286338 TI - Community pharmacists' perceptions about pharmaceutical care of OTC western medicine: a survey in Harbin of China. AB - BACKGROUND: In China, increasingly OTC-western medicine is obtained at the community pharmacy. It is unknown which care the community pharmacists in China provides with such medicines. OBJECTIVE: This study investigated community pharmacists' attitude, practice and perceived barriers about pharmaceutical care of over-the-counter western medicine. Moreover, community pharmacists' suggestions of improvement measures were also collected. METHODS: Questionnaire survey targeting community pharmacist. RESULTS: Respondents generally showed positive attitude towards pharmaceutical care. About 30 % of the respondents reported that they provided pharmaceutical care "whenever necessary", while about 40 % did it "as frequent as possible" or "to all consumers". Respondents considered "ambiguity of the professional role of pharmacists" (50.7 %), "Lack of scientific evidence of over-the-counter western medicine" (42.9), and "Lack of time" (40.0 %) as the main barriers. The 3 most important improvement measures suggested were "Formulating or refining legislation to clarify the legal professional role of pharmacists with respect to western medicine" (63.2 %), "Promoting public education of pharmacist role" (50.7 %), and "Formulating or refining the standards of pharmacists' practice with respect to western medicine" (50.7 %). CONCLUSION: Community pharmacists in Harbin of China have a relatively positive attitude and intention to provide pharmaceutical care of OTC western medicine. However, lack of professional role definition, limited pharmaceutical knowledge and lack of human and financial resources limited the provision of pharmaceutical care by community pharmacists. PMID- 26286339 TI - A case of exogenous corticosteroid-induced Kaposi's sarcoma that developed after a cure of endogenous hypercortisolism. AB - Case Kaposi's sarcoma (KS) is a malignant vascular tumor that occurs commonly in patients with acquired immunodeficiency syndrome. KS associated with Cushing's syndrome (CS) is unusual, especially in endogenous CS. Here, we report a case of KS associated with glucocorticoid-replacement therapy after surgical treatment for adrenal CS. A 70-year-old man presented with symptoms and signs of CS with a left adrenal mass. Adrenal CS was confirmed by biochemical studies. After left adrenalectomy, he took oral prednisolone (15 mg/day) to prevent adrenal insufficiency. Ten weeks later, numerous raised purple plaques on the lower extremities were newly detected. The biopsy findings were compatible with KS, but anti-HIV antibodies were negative. After withdrawal of glucocorticoid therapy, the skin lesions regressed completely. CONCLUSION: In this case, KS developed after the use of exogenous corticosteroid but not during endogenous hypercortisolism. This finding suggests that endogenous and exogenous corticosteroid play different roles in the development of KS. PMID- 26286340 TI - Adverse drug reactions experience in a teaching hospital in Jordan. AB - BACKGROUND: Adverse drug reactions (ADRs) represent a major health care problem. OBJECTIVE: To identify the most common ADRs, drugs implicated in ADRs, and to assess their causality, severity, preventability and risk factors predisposing to reported ADRs in Jordan. SETTING: Al-Karak teaching hospital, southern of Jordan. Method A cross sectional observational study was carried out for 11 months from January to November 2013. Suspected ADRs were recorded in ADRs report forms and analyzed for causality, severity, and preventability. MAIN OUTCOME MEASURE: Most common ADRs, drugs involved in these ADRs, causality, severity, and preventability of suspected ADRs. RESULTS: A total of 64 reports were received. Some patients suffered more than one ADR. The total number of ADRs identified was 108. Forty one drugs were involved in causing these ADRs. About 2/3 of adverse reactions (73.4 %) did not cause admission to the hospital, whereas 26.6 % of the ADRs resulted in admission. Majority of the ADRs were type A (62.5 %). Most of ADRs (92.2 %) were assessed as probable. Nearly, 65.6 % of ADRs were categorized as mild. Majority of ADRs were assessed as "not preventable" (75 %). The most common classes of drugs involved in ADRs were antibiotics, analgesics, vaccines and antiepileptics. The most commonly identified ADRs were abdominal pain, skin rash, shortness of breath, fever, upper gastrointestinal bleeding and vomiting. Risk factors contributed to ADRs were age and polypharmacy. CONCLUSION: Jordanian healthcare providers should be aware of the importance of detecting and reporting ADRs, in order to prevent and reduce the incidence of ADRs. Awareness of risk factors predisposing to ADRs may help in identifying patients with higher risk and therefore reducing the risk of these ADRs and improving patient outcome. PMID- 26286341 TI - Armed Conflict, Substance Use and HIV: A Global Analysis. AB - Armed conflict is frequently assumed to be a contributor to the global HIV epidemic, but existing evidence is sparse. We examined the relationship between armed conflict between 2002 and 2008 and HIV disability life years (DALYs) in 2010 among WHO Member States. Using partial least squares analysis we also examined moderation of the armed conflict-HIV link by two susceptibility constructs (background risk, substance use) and one vulnerability mediator (numbers of refugees, people on ART, and total HIV spending). Background risk directly impacted HIV DALYs (p < 0.05), substance use moderated the conflict-HIV relationship (p < 0.01). The vulnerability construct mediated the conflict-HIV association (p < 0.01). Findings underscore the need to align HIV prevention/intervention efforts with pre-existing HIV burden and reduce the impact of natural disasters on the populace in conflict-affected states. Integration of substance prevention/harm reduction programs within national HIV responses, attention to most-at-risk populations and increased surveillance/treatment of drug resistant HIV and TB is warranted. PMID- 26286342 TI - Correlates of Alcohol Use Among Patrons of Alcohol Consumption Venues in Botswana. AB - This study evaluated the correlates of three alcohol measures using a cross sectional survey conducted among patrons of alcohol-serving venues in Gaborone, Botswana from October 2012 to February 2013. Using logistic regression, we found that engaging in higher levels of sexual risk behaviors was significantly associated with frequent drinking (at least 3 times a week), heavy episodic drinking (more than 6 standard units of alcohol at least weekly) and probable alcohol dependence (AUDIT score >=20). Additionally, having higher levels of alcohol expectancies that increase the risk of HIV infection was significantly associated with probable alcohol dependence. Although HIV knowledge was generally high in this population, there is need for HIV prevention and alcohol harm reduction efforts to address the role of alcohol in increasing HIV risk and encourage the adoption of safer drinking patterns and the modification of alcohol expectancies. PMID- 26286343 TI - Community Collectivization and Consistent Condom Use Among Female Sex Workers in Southern India: Evidence from Two Rounds of Behavioral Tracking Surveys. AB - Community collectivization is an integral part of condom use and HIV risk reduction interventions among key population. This study assesses community collectivization among female sex workers (FSWs), and explores its relationship with sex workers' consistent condom use (CCU) with different partners considering the interaction effect of time and collectivization. Data were drawn from two rounds of cross-sectional surveys collected during 2010 (N1 = 1986) and 2012 (N2 = 1973) among FSWs in Andhra Pradesh, India. Results of the multiple logistic regression analysis show that, CCU with regular and occasional clients increased over the inter-survey period among FSWs with a high collective efficacy (AOR 2.9 and 6.1) and collective agency (AOR 14.4 and 19.0) respectively. The association of high levels of collectivization with CCU and self-efficacy for condom use are central to improve the usefulness and sustainability of HIV prevention programs worldwide. PMID- 26286344 TI - Hepatectomy of segment 4b and 5 with extrahepatic bile duct resection for pT2 gallbladder carcinoma is valid: a single-institution result. AB - The results of surgical treatment for T2 gallbladder carcinoma are equivocal, while the precise preoperative TNM staging and localization of gallbladder carcinoma are difficult. The aim of this study was to report the validity of segment 4b and 5 (S4b+5) hepatectomy with extrahepatic bile duct resection for these tumors. We reviewed 30 patients with pT2 gallbladder cancer who underwent S4b+5 hepatectomy with extrahepatic bile duct resection. The median number of lymph nodes retrieved in the S4b+5 hepatectomy group was 11 (0-23) nodes, and lymph node metastasis was observed in 9 of 30 (30%) cases. Although all surgical margins were macroscopically negative, 4 of the 30 patients (13%) had pathologically positive margins. The overall survival rate of patients was 85.1% at 5 years. Of the 30 patients with S4b+5 hepatectomy, surgical margin alone was analyzed as a prognostic factor in univariate and multivariate analysis. The survival rate was comparable between the tumor on the hepatic side and peritoneal side (P = 0.856). Nine patients with additional S4b+5 hepatectomy after simple cholecystectomy because of incidental diagnosis of gallbladder cancer also had comparable survival compared to the remaining 21 patients with simultaneous S4b+5 hepatectomy (P = 0.624). S4b+5 hepatectomy with extrahepatic bile duct resection could be good treatment modality for T2 gallbladder cancers because precise preoperative diagnosis of tumor depth, location, and lymph node metastasis for these tumors is difficult. PMID- 26286345 TI - The immunopathology of systemic sclerosis. PMID- 26286346 TI - White House boosts public health role in response to heroin epidemic. PMID- 26286347 TI - A new record of Myxobolus brachysporus and M. israelensis in the tilapia (Oreochromis niloticus) collected from the Nile River, Egypt. AB - The present study was carried out as part of an ongoing general survey for myxosporean parasites infecting tilapias in the River Nile, Egypt. In the present study, 77 Nile tilapia (Oreochromis niloticus) were collected from boat landing sites at Beni-Suef governorate, Egypt and examined for the myxosporean infection. The infection was encountered as a huge number of free spores in the kidney and the spleen. The infection showed a prevalence of 51.9% (40/77) for Myxobolus brachysporus while it was 25.9% (20/77) for Myxobolus israelensis. Mature spores of M. brachysporus were ellipsoidal and measured 8.6 * 13.2 MUm. The polar capsules were subcircular with 5-6 filament turns and measured 4.7 * 3.6 MUm. Spores of M. israelensis were ellipsoidal in the frontal view and fusiform in the lateral view. Spore measurements were 13.4 MUm long and 8.7 MUm wide. The polar capsules were elongated with 6-7 filament coils and measured 8.6 * 3.1 MUm. The findings presented here proved that tilapia fishes in the Nile River are still suffering from infections with Myxobolus species. Therefore, further studies should be carried out to survey the Myxobolus infection among tilapias under culture conditions to clarify the pathological impacts of this parasite in tilapias aquaculture. PMID- 26286348 TI - Urine colour change as an indicator of change in daily water intake: a quantitative analysis. AB - PURPOSE: Urine colour (U Col) is simple to measure, differs between low-volume and high-volume drinkers, and is responsive to changes in daily total fluid intake (TFI). However, to date, no study has quantified the relationship between a change in TFI and the resultant change in U Col. This analysis aimed to determine the change in TFI needed to adjust 24-h U Col by 2 shades on an 8 colour scale, and to evaluate whether starting U Col altered the relationship between the change in TFI and change in U Col. METHODS: We performed a pooled analysis on data from 238 healthy American and European adults (50 % male; age, 28 (sd 6) years; BMI 22.9 (sd 2.6) kg/m(2)), and evaluated the change in TFI, urine volume (U Vol), and specific gravity (U SG) associated with a change in U Col of 2 shades. RESULTS: The mean [95 % CI] change in TFI and U Vol associated with a decrease in U Col by 2 shades (lighter) was 1110 [914;1306] and 1011 [851;1172] mL/day, respectively, while increasing U Col by 2 shades (darker) required a reduction in TFI and U Vol of -1114 [-885;-1343] and -977 [-787;-1166] mL/day. The change in U Col was accompanied by changes in U SG (lighter urine: .008 [-.007;-.010]; darker urine: +.008 [.006;.009]). Starting U Col did not significantly impact the TFI change required to modify U Col by 2 shades. CONCLUSIONS: Our results suggest a quantifiable relationship between a change in daily TFI and the resultant change in U Col, providing individuals with a practical means for evaluating and adjusting hydration behaviours. PMID- 26286350 TI - A national survey of Mohs micrographic surgery in the U.K. PMID- 26286349 TI - In vitro fermentation of nuts results in the formation of butyrate and c9,t11 conjugated linoleic acid as chemopreventive metabolites. AB - PURPOSE: The consumption of foods rich in dietary fiber and polyunsaturated fatty acids such as nuts can contribute to a healthy diet. Therefore, the formation of fermentation end-products which might exert chemopreventive effects regarding colon cancer was investigated after an in vitro simulated digestion and fermentation of nuts using human fecal microbiota. METHODS: Fermentation supernatants (FS) and pellets (FP) were obtained after an in vitro fermentation of hazelnuts, almonds, macadamia, pistachios and walnuts. Short-chain fatty acids (SCFA) and bile acids (BA) in FS as well as fatty acids in FP were analyzed via gas chromatography. Malondialdehyde (MDA) levels in FS were determined photometrically. RESULTS: Fermentation of nuts resulted in 1.9- to 2.8-fold higher concentrations of SCFA compared to the control and a shift of molar ratios toward butyrate production. In vitro fermentation resulted in the formation of vaccenic acid (C18:1t11, 32.1 +/- 3.2 % FAME; fatty acid methyl ester) and conjugated linoleic acid (c9,t11 CLA, 2.4 +/- 0.7 % FAME) exclusively in fermented walnut samples. Concentrations of secondary BA deoxycholic-/iso deoxycholic acid (6.8-24.1-fold/4.9-10.9-fold, respectively) and levels of MDA (1.3-fold) were significantly reduced in fermented nut samples compared to the control. CONCLUSION: This is the first study that demonstrates the ability of the human fecal microbiota to convert polyunsaturated fatty acids from walnuts to c9,t11 CLA as a potential chemopreventive metabolite. In addition, the production of butyrate and reduction in potential carcinogens such as secondary BA and lipid peroxidation products might contribute to the protective effects of nuts regarding colon cancer development. PMID- 26286351 TI - Adherence and competence in two manual-guided therapies for co-occurring substance use and posttraumatic stress disorders: clinician factors and patient outcomes. AB - BACKGROUND: The challenges of implementing and sustaining evidence-based therapies into routine practice have been well-documented. OBJECTIVES: This study examines the relationship among clinician factors, quality of therapy delivery, and patient outcomes. METHODS: Within a randomized controlled trial, 121 patients with current co-occurring substance use and posttraumatic stress disorders were allocated to receive either manualized Integrated Cognitive Behavioral Therapy (ICBT) or Individual Addiction Counseling (IAC). Twenty-two clinicians from seven addiction treatment programs were trained and supervised to deliver both therapies. Clinician characteristics were assessed at baseline; clinician adherence and competence were assessed over the course of delivering both therapies; and patient outcomes were measured at baseline and 6-month follow-up. RESULTS: Although ICBT was delivered at acceptable levels, clinicians were significantly more adherent to IAC (p < 0.05). At session 1, clinical female gender (p < 0.05) and lower education level (p < 0.05) were predictive of increased clinician adherence and competence across both therapies. Adherence and competence at session 1 in either therapy were significantly predictive of positive patient outcomes. ICBT adherence (p < 0.05) and competence (p < 0.01) were predictive of PTSD symptom reduction, whereas IAC adherence (p < 0.01) and competence (p < 0.01) were associated with decreased drug problem severity. CONCLUSIONS: The differential impact of adherence and competence for both therapy types is consistent with their purported primary target: ICBT for PTSD and IAC for substance use. These findings also suggest the benefits of considering clinician factors when implementing manual-guided therapies. Future research should focus on diverse clinician samples, randomization of clinicians to therapy type, and prospective designs to evaluate models of supervision and quality monitoring. PMID- 26286352 TI - The association between alcohol use and cardiovascular disease among people living with HIV: a systematic review. AB - BACKGROUND: People living with HIV-infection (PLWH) have higher prevalence and earlier onset of cardiovascular disease (CVD), compared to uninfected populations. It is unclear how alcohol consumption is related to CVD among PLWH. OBJECTIVES: To summarize the current literature and strength of evidence regarding alcohol consumption as a risk factor for CVD among PLWH, to generate summary estimates for the effect of alcohol consumption on CVD outcomes, and to make recommendations for clinical practice and future research based on the findings and limitations of existing studies. METHODS: A systematic review was conducted using Pubmed/Medline to identify relevant peer-reviewed articles published between 1 January 1999 and 1 January 2014. After critical review of the literature, 13 studies were identified. Risk ratios were extracted or calculated and sample size weighted summary estimates were calculated. RESULTS: The prevalence of a CVD diagnosis or event ranged from 5.7-24.0%. The weighted pooled crude effect sizes were 1.75 (95% CI 1.06, 3.17) for general and 1.78 (95% CI 1.09, 2.93) for heavy alcohol use on CVD. The pooled adjusted effect size was 1.37 (95% CI 1.02, 1.84) for heavy alcohol use on CVD. Pooled estimates differed by CVD outcome and alcohol measure; alcohol consumption was most significant for cerebral/ischemic events. CONCLUSION: HIV clinicians should consider risk factors that are not included in the traditional risk factor framework, particularly heavy alcohol consumption. Neglect of this risk factor may lead to underestimation of risk, and thus under-treatment among PLWH. PMID- 26286353 TI - Ethnic inequalities in dental caries among adults in East London. AB - BACKGROUND: This study explored ethnic inequalities in dental caries among adults and assessed the role of socioeconomic position (SEP) in explaining those inequalities. METHODS: We analysed data on 2013 adults aged 16-65 years, from the East London Oral Health Inequality (ELOHI) Study, which included a random sample of adults and children living in East London in 2009-10. Participants completed a questionnaire and were clinically examined for dental caries at home. Dental caries was measured using the number of decayed, missing and filled teeth or DMFT index. Ethnic inequalities in dental caries were assessed in negative binomial regression models before and after adjustment for demographic (sex and age groups) and SEP measures (education and socioeconomic classification). RESULTS: White Eastern European and White Other had higher DMFT, whereas all Asian (Pakistani, Indian, Bangladeshi and Other) and all Black (African, Caribbean and Other) ethnic groups had lower DMFT than White British. Similar inequalities were found for the number of filled and missing teeth, but there were no differences in the number of decayed teeth between ethnic groups. CONCLUSIONS: This study showed considerable disparities in dental caries between and within the major ethnic categories, which were independent of demographics and SEP. PMID- 26286354 TI - Circulating microRNAs as Candidate Biomarkers for the Surveillance of Melanoma Patients. PMID- 26286355 TI - Microbial activity in forest soil reflects the changes in ecosystem properties between summer and winter. AB - Understanding the ecology of coniferous forests is very important because these environments represent globally largest carbon sinks. Metatranscriptomics, microbial community and enzyme analyses were combined to describe the detailed role of microbial taxa in the functioning of the Picea abies-dominated coniferous forest soil in two contrasting seasons. These seasons were the summer, representing the peak of plant photosynthetic activity, and late winter, after an extended period with no photosynthate input. The results show that microbial communities were characterized by a high activity of fungi especially in litter where their contribution to microbial transcription was over 50%. Differences in abundance between summer and winter were recorded for 26-33% of bacterial genera and < 15% of fungal genera, but the transcript profiles of fungi, archaea and most bacterial phyla were significantly different among seasons. Further, the seasonal differences were larger in soil than in litter. Most importantly, fungal contribution to total microbial transcription in soil decreased from 33% in summer to 16% in winter. In particular, the activity of the abundant ectomycorrhizal fungi was reduced in winter, which indicates that plant photosynthetic production was likely one of the major drivers of changes in the functioning of microbial communities in this coniferous forest. PMID- 26286356 TI - Recent developments in the diagnosis and treatment of pulmonary embolism. AB - Due to the nonspecific symptoms of the condition, a diagnosis of acute pulmonary embolism (PE) is frequently considered. However, PE will only be confirmed in 10 20% of patients. Because the imaging test of choice, computed tomography pulmonary angiography (CTPA), is costly and associated with radiation exposure and other complications, a validated diagnostic algorithm consisting of a clinical decision rule and D-dimer test should be used to safely exclude PE in 20 30% of patients without the need for CTPA. Recently, the age-adjusted D-dimer threshold has been validated, and this has increased the proportion of patients at older age in whom PE can be excluded without CTPA. Initial therapeutic management of PE depends on the risk of short-term PE-related mortality. Haemodynamically unstable patients should be closely monitored and receive thrombolytic therapy unless contraindicated because of an unacceptably high bleeding risk, whereas patients with low-risk PE may be safely discharged early from hospital or receive only outpatient treatment. The PESI score and Hestia decision rule are available to select patients in whom early discharge or outpatient treatment will be safe, although the safety of these strategies should be confirmed in additional studies. Standard PE therapy consists of low molecular weight heparin (LMWH) followed by vitamin K antagonists (VKAs). Recently, several nonvitamin K-dependent oral anticoagulants have been shown to be as effective as LMWH/VKAs, and maybe safer. Determining the optimal duration of treatment for a first unprovoked PE remains a challenge, although clinical prediction rules for estimating the risk of recurrence of venous thromboembolism and anticoagulation associated haemorrhage are under investigation. Using these prediction rules may lead to both more standardized and more individualized long-term treatment of PE. PMID- 26286357 TI - Restoration of cytoskeletal and membrane tethering defects but not defects in membrane trafficking in the intestinal brush border of mice lacking both myosin Ia and myosin VI. AB - Myosin Ia (Myo1a), the most prominent plus-end directed motor and myosin VI (Myo6) the sole minus-end directed motor, together exert opposing tension between the microvillar (MV) actin core and the apical brush border (BB) membrane of the intestinal epithelial cell (IEC). Mice lacking Myo1a or Myo6 each exhibit a variety of defects in the tethering of the BB membrane to the actin cytoskeleton. Double mutant (DM) mice lacking both myosins revealed that all the defects observed in either the Myo1a KO or Snell's waltzer (sv/sv) Myo6 mutant mouse are absent. In isolated DM BBs, Myo1a crosslinks between MV membrane and MV actin core are absent but the gap (which is lost in Myo1a KO) between the MV core and membrane is maintained. Several myosins including Myo1c, d, and e and Myo5a are ectopically recruited to the BB. Consistent with the restoration of membrane tethering defects by one or more of these myosins, upward ATP-driven shedding of the BB membrane, which is blocked in the Myo1a KO, is restored in the DM BB. However, Myo1a or Myo6 dependent defects in expression of membrane proteins that traffic between the BB membrane and endosome (NaPi2b, NHE3, CFTR) are not restored. Compared to controls, Myo1a KO, sv/sv mice exhibit moderate and DM high levels of hypersensitivity to dextran sulfate sodium-induced colitis. Consistent with Myo1a and Myo6 playing critical roles in maintaining IEC integrity and response to injury, DM IECs exhibit increased numbers of apoptotic nuclei, above that reported for Myo1a KO. PMID- 26286361 TI - Rapid sequestration of rock avalanche deposits within glaciers. AB - Topographic development in mountainous landscapes is a complex interplay between tectonics, climate and denudation. Glaciers erode valleys to generate headwall relief, and hillslope processes control the height and retreat of the peaks. The magnitude-frequency of these landslides and their long-term ability to lower mountains above glaciers is poorly understood; however, small, frequent rockfalls are currently thought to dominate. The preservation of rarer, larger, landslide deposits is exceptionally short-lived, as they are rapidly reworked. The 2013 Mount Haast rock avalanche that failed from the slopes of Aoraki/Mount Cook, New Zealand, onto the glacier accumulation zone below was invisible to conventional remote sensing after just 3 months. Here we use sub-surface data to reveal the now-buried landslide deposit, and suggest that large landslides are the primary hillslope erosion mechanism here. These data show how past large landslides can be identified in accumulation zones, providing an untapped archive of erosive events in mountainous landscapes. PMID- 26286358 TI - Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy. AB - Enfuvirtide (T20), is the first HIV fusion inhibitor approved for treatment of HIV/AIDS patients who fail to respond to the current antiretroviral drugs. However, its clinical application is limited because of short half-life, drug resistance and cross-reactivity with the preexisting antibodies in HIV-infected patients. Using an artificial peptide strategy, we designed a peptide with non native protein sequence, AP3, which exhibited potent antiviral activity against a broad spectrum of HIV-1 strains, including those resistant to T20, and had remarkably longer in vivo half-life than T20. While the preexisting antibodies in HIV-infected patients significantly suppressed T20's antiviral activity, these antibodies neither recognized AP3, nor attenuated its anti-HIV-1 activity. Structurally different from T20, AP3 could fold into single-helix and interact with gp41 NHR. The two residues, Met and Thr, at the N-terminus of AP3 form a hook-like structure to stabilize interaction between AP3 and NHR helices. Therefore, AP3 has potential for further development as a new HIV fusion inhibitor with improved antiviral efficacy, resistance profile and pharmacological properties over enfuvirtide. Meanwhile, this study highlighted the advantages of artificially designed peptides, and confirmed that this strategy could be used in developing artificial peptide-based viral fusion inhibitors against HIV and other enveloped viruses. PMID- 26286360 TI - Activity of neutral and alkaline ceramidases on fluorogenic N-acylated coumarin containing aminodiols. AB - Ceramidases catalyze the cleavage of ceramides into sphingosine and fatty acids. Previously, we reported on the use of the RBM14 fluorogenic ceramide analogs to determine acidic ceramidase activity. In this work, we investigated the activity of other amidohydrolases on RBM14 compounds. Both bacterial and human purified neutral ceramidases (NCs), as well as ectopically expressed mouse neutral ceramidase hydrolyzed RBM14 with different selectivity, depending on the N-acyl chain length. On the other hand, microsomes from alkaline ceramidase (ACER)3 knockdown cells were less competent at hydrolyzing RBM14C12, RBM12C14, and RBM14C16 than controls, while microsomes from ACER2 and ACER3 overexpressing cells showed no activity toward the RBM14 substrates. Conversely, N acylethanolamine-hydrolyzing acid amidase (NAAA) overexpressing cells hydrolyzed RBM14C14 and RBM14C16 at acidic pH. Overall, NC, ACER3, and, to a lesser extent, NAAA hydrolyze fluorogenic RBM14 compounds. Although the selectivity of the substrates toward ceramidases can be modulated by the length of the N-acyl chain, none of them was specific for a particular enzyme. Despite the lack of specificity, these substrates should prove useful in library screening programs aimed at identifying potent and selective inhibitors for NC and ACER3. PMID- 26286362 TI - Response to "Comments on 'A Simple Device for Syringe-to-Syringe Transfer During Lipofilling'". PMID- 26286363 TI - Comments on "A Simple Device for Syringe-to-Syringe Transfer During Lipofilling". PMID- 26286364 TI - Evaluation of the 10-year history of a 2-day standardized laparoscopic surgical skills training program at Kyushu University. AB - PURPOSE: Laparoscopic and open surgical skills differ distinctly from one another. Our institute provides laparoscopic surgical skills training for currently active surgeons throughout Japan. This study was performed to evaluate the effectiveness of our 2-day standardized laparoscopic surgical skills training program over its 10-year history. METHODS: We analyzed the data on trainee characteristics, outcomes of skills assessments at the beginning and end of the program, and self-assessment after 6 months using a questionnaire survey. RESULTS: From January 2004 to December 2013, 914 surgeons completed the 2-day training program. Peaks in postgraduate years of experience occurred at years 2, 8, and 17. Suturing and knot tying times were significantly shorter at the end than beginning of the program (p < 0.001). However, the numbers of misplaced and loose sutures, maximum misplacement distance, and number of injuries to the rubber sheet were significantly higher at the end of the program (p < 0.001). A questionnaire at 6 months post-training revealed significant improvements in the overall skills and forceps manipulation (p < 0.0001) and a significantly shorter mean operation time for laparoscopic cholecystectomy (p < 0.001). CONCLUSION: Our 2-day training program for active Japanese surgeons is thus considered to be effective; however, continued voluntary training is important and further outcomes assessments are needed. PMID- 26286366 TI - Trends in the Surgical Management of Crohn's Disease. AB - INTRODUCTION: Although medical management of Crohn's disease has changed in recent years, it is unclear whether surgical management has altered. We examined rate changes of surgical interventions, stoma constructions, and subset of ileostomy and colostomy constructions. MATERIALS AND METHODS: We reviewed the Nationwide Inpatient Sample database from 1988 to 2011. We examined the number of Crohn's-related operations and stoma constructions, including ileostomies and colostomies; a multivariable logistic regression model was developed. RESULTS: A total of 355,239 Crohn's-related operations were analyzed. Operations increased from 13,955 in 1988 to 17,577 in 2011, p < 0.001. Stoma construction increased from 2493 to 4283, p < 0.001. The subset of ileostomies increased from 1201 to 3169, p < 0.001 while colostomies decreased from 1351 to 1201, p = 0.05. Operation percentages resulting in stoma construction increased from 18 to 24 %, p < 0.001. Weight loss (OR 2.25, 95 % CI 1.88, 2.69) and presence of perianal fistulizing disease (OR 2.91, 95 % CI 2.31, 3.67) were most predictive for requiring stoma construction. CONCLUSIONS: Crohn's-related surgical interventions and stoma constructions have increased. The largest predictors for stoma construction are weight loss and perianal fistulizing disease. As a result, nutrition should be optimized and the early involvement of a multidisciplinary team should be considered. PMID- 26286365 TI - Perioperative Blood Transfusion and Postoperative Outcome in Patients with Crohn's Disease Undergoing Primary Ileocolonic Resection in the "Biological Era". AB - BACKGROUND: Perioperative blood transfusion has been shown to be associated with inflammatory response and immunosuppression. Patients receiving blood transfusion may have an increased risk for developing postoperative morbidities. The impact of blood transfusion on the postoperative recurrence of Crohn's disease (CD) has been controversial. The aim of this study was to assess the effect of blood transfusion on postoperative outcomes in CD in the current biological era. METHODS: This historical cohort study involved data collection and analysis of CD patients who underwent the index ileocolonic resection in our institution between 2000 and 2012. Postoperative complications were compared between the transfused and nontransfused patients. The effects of perioperative blood transfusion on postoperative complications and disease recurrence were analyzed with both univariate and multivariate analyses. RESULTS: A total of 318 patients were included in the study, and 52 of them (16.5 %) received perioperative blood transfusion. Blood transfusion was found to be associated with an increased risk of postoperative infectious and noninfectious complications both in univariate (P < 0.001 for each) and multivariable analyses (infectious complications: odds ratio [OR] = 8.73, 95 % confidence interval [CI] 2.85-26.78, P < 0.001; noninfectious complications: OR = 3.64, 95 % CI 1.30-10.18; P = 0.014). In addition, the Cox regression model indicated that blood transfusion was associated with both surgical (hazard ratio [HR] = 3.43, 95 % CI 1.92-6.13; P < 0.001) and endoscopic (HR = 2.08, 95 % CI 1.38-3.14; P < 0.001) CD recurrence following the index surgery. CONCLUSION: Adverse outcomes after perioperative blood transfusion for the primary ileocolonic resection for CD resemble findings in surgery for other diseases. The presumed immunosuppressive effect of blood transfusion did not confer any protective effect on disease recurrence. PMID- 26286367 TI - Incidence and Risk Factors Associated with Readmission After Surgical Treatment for Adrenocortical Carcinoma. AB - BACKGROUND: Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis. Given the lack of data on readmission after resection of ACC, the objective of the current study was to define the incidence of readmission, as well as identify risk factors associated with readmission among patients with ACC who underwent surgical resection. METHODS: Two hundred nine patients who underwent resection of ACC between January 1993 and December 2014 at 1 of 13 major centers in the USA were identified. Demographic and clinicopathological data were collected and analyzed relative to readmission. RESULTS: Median patient age was 52 years, and 62 % of the patients were female. Median tumor size was 12 cm, and the majority of patients had an American Society of Anesthesiologists (ASA) class of 3-4 (n = 85, 56 %). The overall incidence of readmission within 90 days from surgery was 18 % (n = 38). Factors associated with readmission included high ASA class (odds ratio (OR), 4.88 (95 % confidence interval (CI), 1.75 13.61); P = 0.002), metastatic disease on presentation (OR, 2.98 (95 % CI, 1.37 6.46); P = 0.006), EBL (>700 mL: OR, 2.75 (95 % CI, 1.16-6.51); P = 0.02), complication (OR, 1.91 (95 % CI, 1.20-3.05); P = 0.007), and prolonged length of stay (LOS; >=9 days: OR, 4.12 (95 % CI, 1.88-9.01); P < 0.001). On multivariate logistic regression, a high ASA class (OR, 4.01 (95 % CI, 1.44-11.17); P = 0.008) and metastatic disease on presentation (OR, 3.44 (95 % CI, 1.34-8.84); P = 0.01) remained independently associated with higher odds of readmission. CONCLUSION: Readmission following surgery for ACC was common as one in five patients experienced a readmission. Patients with a high ASA class and metastatic disease on presentation were over four and three times more likely to be readmitted after surgical treatment for ACC, respectively. PMID- 26286368 TI - Initial Misdiagnosis of Proximal Pancreatic Adenocarcinoma Is Associated with Delay in Diagnosis and Advanced Stage at Presentation. AB - INTRODUCTION: Delay in diagnosis of pancreatic ductal adenocarcinoma (PDAC) is associated with decreased survival. The effect of an initial misdiagnosis on delay in diagnosis and stage of PDAC is unknown. METHODS: This study is a retrospective review (2000-2010) from a University-based cancer center of new diagnoses of proximal PDAC. RESULTS: Of 313 patients, 98 (31.3 %) had an initial misdiagnosis. Misdiagnosed patients were younger, 62.8 +/- 12.6 vs. 68.0 +/- 10.1 (p < 0.001). The most common initial misdiagnoses were: gallbladder disease, gastroesophageal reflux disease, and peptic ulcer disease. After excluding patients with prior cholecystectomy, 14.2 % were misdiagnosed with gallbladder disease and underwent cholecystectomy before PDAC diagnosis. Misdiagnosed patients had higher rates of abdominal pain (p < 0.001), weight loss (p = 0.04), and acute pancreatitis (p < 0.001) and lower rate of jaundice (p < 0.001). Median time between symptoms to PDAC diagnosis was longer in misdiagnosed: 4.2 months vs. 1.4 (p < 0.001). Median time from contact with medical provider to axial imaging was longer in misdiagnosed (p < 0.001). Rate of stages III-IV disease at diagnosis was higher in misdiagnosed: 61.2 vs. 43.7 % (p = 0.004), with a 1.4 (95 % confidence interval (CI), 1.12-1.74) higher risk of stages III-IV disease at diagnosis; however, there was no difference in median overall survival in misdiagnosed patients (9.6 months in misdiagnosed vs. 10.3 months in correctly diagnosed, p = 0.69). CONCLUSIONS: Initial misdiagnosis of patients with proximal PDAC is associated with delay in diagnosis and higher risk of locally advanced or advanced disease at time of PDAC diagnosis. PMID- 26286369 TI - The objects of visuospatial short-term memory: Perceptual organization and change detection. AB - We used a colour change-detection paradigm where participants were required to remember colours of six equally spaced circles. Items were superimposed on a background so as to perceptually group them within (a) an intact ring-shaped object, (b) a physically segmented but perceptually completed ring-shaped object, or (c) a corresponding background segmented into three arc-shaped objects. A nonpredictive cue at the location of one of the circles was followed by the memory items, which in turn were followed by a test display containing a probe indicating the circle to be judged same/different. Reaction times for correct responses revealed a same-object advantage; correct responses were faster to probes on the same object as the cue than to equidistant probes on a segmented object. This same-object advantage was identical for physically and perceptually completed objects, but was only evident in reaction times, and not in accuracy measures. Not only, therefore, is it important to consider object-level perceptual organization of stimulus elements when assessing the influence of a range of factors (e.g., number and complexity of elements) in visuospatial short term memory, but a more detailed picture of the structure of information in memory may be revealed by measuring speed as well as accuracy. PMID- 26286370 TI - Stability and Conversion of Tin Zintl Anions in Liquid Ammonia Investigated by NMR spectroscopy. AB - Homoatomic polyanions of post-transition main-group metals, namely, Zintl anions, are precast in analogous Zintl phases and can react in solution to form new materials. Despite comprehensible reaction approaches, the formed products cannot be planned in advance, as hitherto undetected and therefore disregarded side reactions take place. The outcomes and interpretations of the reactions of Zintl anions are so far based mainly on crystal structures, which only allow characterization of the product that has the lowest solubility. Here we present the results of our investigation of the stability of highly charged tin Zintl anions in liquid ammonia, which is not exclusively based on solution effects but also on the oxidative influence of the solvent. This allows for a deeper understanding of the ongoing processes in solution and opens doors to the directed synthesis of transition metal complexes of Sn4 (4-) , here shown by its reactivity towards MesCu. PMID- 26286371 TI - Singapore Grouper Iridovirus ORF75R is a Scaffold Protein Essential for Viral Assembly. AB - Singapore Grouper Iridovirus (SGIV) is a member of nucleo cytoplasmic large DNA viruses (NCLDV). This paper reports the functional analysis of ORF75R, a major structural protein of SGIV. Immuno fluorescence studies showed that the protein was accumulated in the viral assembly site. Immunogold-labelling indicated that it was localized between the viral capsid shell and DNA core. Knockdown of ORF75R by morpholinos resulted in the reduction of coreshell thickness, the failure of DNA encapsidation, and the low yield of infectious particles. Comparative proteomics further identified the structural proteins affected by ORF75R knockdown. Two-dimensional gel electrophoresis combined with proteomics demonstrated that ORF75R was phosphorylated at multiple sites in SGIV-infected cell lysate and virions, but the vast majority of ORF75R in virions was the dephosphorylated isoform. A kinase assay showed that ORF75R could be phosphorylated in vitro by the SGIV structural protein ORF39L. Addition of ATP and Mg(2+) into purified virions prompted extensive phosphorylation of structural proteins and release of ORF75R from virions. These data suggest that ORF75R is a novel scaffold protein important for viral assembly and DNA encapsidation, but its phosphorylation facilitates virion disassembly. Compared to proteins from other viruses, we found that ORF75R shares common features with herpes simplex virus VP22. PMID- 26286373 TI - NMR spectral properties of the tetramantanes - nanometer-sized diamondoids. AB - Tetramantanes, and all diamondoid hydrocarbons, possess carbon frameworks that are superimposable upon the cubic diamond lattice. This characteristic is invaluable in assigning their (1)H and (13)C NMR spectra because it translates into repeating structural features, such as diamond-cage isobutyl moieties with distinctively complex methine to methylene signatures in COSY and HMBC data, connected to variable, but systematic linkages of methine and quaternary carbons. In all tetramantane C22H28 isomers, diamond-lattice structures result in long range (4)JHH, W-coupling in COSY data, except where negated by symmetry; there are two highly symmetrical and one chiral tetramantane (showing seven (4)JHH). Isobutyl-cage methines of lower diamondoids and tetramantanes are the most shielded resonances in their (13)C spectra (<29.5 ppm). The isobutyl methylenes are bonded to additional methines and at least one quaternary carbon in the tetramantanes. W-couplings between these methines and methylenes clarify spin network interconnections and detailed surface hydrogen stereochemistry. Vicinal couplings of the isobutyl methylenes reveal positions of the quaternary carbons: HMBC data then tie the more remote spin systems together. Diamondoid (13) C NMR chemical shifts are largely determined by alpha and beta effects, however gamma shielding effects are important in [123]tetramantane. (1)H NMR chemical shifts generally correlate with numbers of 1,3-diaxial H-H interactions. Tight van der Waals contacts within [123]tetramantane's molecular groove, however, form improper hydrogen bonds, deshielding hydrogen nuclei inside the groove, while shielding those outside, indicated by Deltadelta of 1.47 ppm for geminal hydrogens bonded to C-3,21. These findings should be valuable in future NMR studies of diamondoids/nanodiamonds of increasing size. PMID- 26286372 TI - Long- and Short-Range Electrostatic Fields in GFP Mutants: Implications for Spectral Tuning. AB - The majority of protein functions are governed by their internal local electrostatics. Quantitative information about these interactions can shed light on how proteins work and allow for improving/altering their performance. Green fluorescent protein (GFP) and its mutation variants provide unique optical windows for interrogation of internal electric fields, thanks to the intrinsic fluorophore group formed inside them. Here we use an all-optical method, based on the independent measurements of transition frequency and one- and two-photon absorption cross sections in a number of GFP mutants to evaluate these internal electric fields. Two physical models based on the quadratic Stark effect, either with or without taking into account structural (bond-length) changes of the chromophore in varying field, allow us to separately evaluate the long-range and the total effective (short- and long-range) fields. Both types of the field quantitatively agree with the results of independent molecular dynamic simulations, justifying our method of measurement. PMID- 26286374 TI - Perceived Relevance of Gender-Specific Differences in Gastrointestinal Medicine and Surgery: Results of a Survey. AB - BACKGROUND: The recognition of the relevance of sex and gender differences in medicine has significantly increased in the last 20 years. Nonetheless, the implementation of these aspects into clinical practice still remains to be attained. In particular, while sex differences - which refer to biological attributes - are widely accepted, gender concepts - which include sociocultural and psychological properties - are frequently treated with diffidence. METHODS: In December 2012 and January 2013, all members of the German Society for General and Abdominal Surgery (DGAV) were invited to participate in an online-based survey to determine the relevance and incorporation of sex and gender aspects in gastrointestinal medicine and surgery. RESULTS: 493 (13.4%) of the 3,689 members of the DGAV participated in the survey. More than 50% of the participants reported including sex and gender aspects into consultation, diagnosis, and management at least occasionally. However, 44% reported no knowledge of the formal definition of 'gender medicine', suggesting potential differences in the perception of the notion of gender. CONCLUSION: The participants of the survey demonstrated vast knowledge about sex differences, while gender attributes were generally neglected. Since gender features are critically relevant for prevention as well as during medical consultation, we suggest this area as a potential target for further training initiatives. PMID- 26286376 TI - Identification of Bufavirus-1 and Bufavirus-3 in Feces of Patients with Acute Diarrhea, China. AB - Bufavirus (BuV) is a newly discovered human parvovirus that has been detected in some countries. The current study was designed to understand the epidemic of BuV in China. Totally 1877 fecal specimens were collected from pediatric and adult patients with acute diarrhea in two large hospitals from 2010 to 2014. BuV was detected in 0.5% (9/1877) of the fecal samples by PCR and subsequent sequencing. The positive patients had a wide age range from 1 month through 60 years (median 24 years old) and 6 were male. A geographic specific pattern was obvious, with significantly higher frequency of BuV presented in Northern than in Southern China. Four BuV-1 and five BuV-3 were determined. Mixed-infections of BuV with sapovirus and novavirus were found in 2 cases, respectively. A temporal clustering was identified, with most positive detection focused in the cold weather. These findings have expanded the current knowledge on the geographic boundaries of BuV circulation. PMID- 26286378 TI - O-GlcNAc cycling enzymes control vascular development of the placenta by modulating the levels of HIF-1alpha. AB - INTRODUCTION: Placental vasculogenesis is essential for fetal growth and development, and is affected profoundly by oxygen tension (hypoxia). Hypoxia inducible factor-1alpha (HIF-1alpha), which is stabilized at the protein level in response to hypoxia, is essential for vascular morphogenesis in the placenta. Many studies suggested that responses to hypoxia is influenced by O GlcNAcylation. O-GlcNAcylation is regulated by O-GlcNAc transferase (OGT) and O GlcNAcase (OGA) that catalyze the addition and removal of O-GlcNAc respectively. METHODS: We generated OGA deficient mice and evaluated OGA(-/-) placentas. The analysis of OGA(-/-) placentas was focused on morphological change and placental vasculogenesis. HIF-1alpha protein stability or transcriptional activity under dysregulation of O-GlcNAcylation were evaluated by Western blot, RT-qPCR and luciferase reporter gene assays in MEFs or MS1 cell line. RESULTS: Deletion of OGA results in defective placental vasculogenesis. OGA(-/-) placentas showed an abnormal placental shape and reduced vasculature in the labyrinth, which caused a developmental delay in the embryos. OGA deletion, which elevates O-GlcNAcylation and downregulates O-GlcNAc transferase (OGT), suppressed HIF-1alpha stabilization and the transcription of its target genes. In contrast, the overexpression of O GlcNAc cycling enzymes enhanced the expression and transcriptional activity of HIF-1alpha. DISCUSSION: These results suggest that OGA plays a critical role in placental vasculogenesis by modulating HIF-1alpha stabilization. Control of O GlcNAcylation is essential for placental development. PMID- 26286377 TI - Hepatic resection of hepatocellular carcinoma after proton beam therapy: A case report. AB - Despite the widespread use of proton beam therapy (PBT) as locoregional therapy, there is currently a lack of histological evidence about the therapeutic effect of PBT for hepatocellular carcinoma (HCC). We present a case of hepatectomy and histological examination of HCC initially treated by PBT. A 76-year-old man with chronic hepatitis C underwent routine ultrasound surveillance, which revealed a 22-mm HCC in segment 4 of the liver. His hepatic reserve was adequate for surgical resection of the tumor; however, he chose to undergo PBT because of his cardiac disease. The patient received 66 Gy in 10 fractions with no toxicity exceeding grade 1. Six months after completion of PBT, contrast computed tomography showed that the tumor had increased in size to 27 mm, and the marginal part of the tumor, but not the central region, was enhanced. Additionally, two new hypervascular nodules were present in segments 5 and 6. The patient underwent surgical treatment 7 months after PBT. The operation and postoperative clinical course were uneventful. Nine months later, however, computed tomography demonstrated new, small, enhanced nodules in the remnant liver (segments 3, 5 and 6) and sacrum. In conclusion, PBT is a valuable treatment for HCC; however, it is difficult to evaluate therapeutic effect of HCC during the early post-irradiation period and provide an alternative treatment if PBT is not effective, especially in HCC cases with good liver function. PMID- 26286375 TI - Discovery, Synthesis, and Optimization of Diarylisoxazole-3-carboxamides as Potent Inhibitors of the Mitochondrial Permeability Transition Pore. AB - The mitochondrial permeability transition pore (mtPTP) is a Ca(2+) -requiring mega-channel which, under pathological conditions, leads to the deregulated release of Ca(2+) and mitochondrial dysfunction, ultimately resulting in cell death. Although the mtPTP is a potential therapeutic target for many human pathologies, its potential as a drug target is currently unrealized. Herein we describe an optimization effort initiated around hit 1, 5-(3-hydroxyphenyl)-N (3,4,5-trimethoxyphenyl)isoxazole-3-carboxamide, which was found to possess promising inhibitory activity against mitochondrial swelling (EC50 <0.39 MUM) and showed no interference on the inner mitochondrial membrane potential (rhodamine 123 uptake EC50 >100 MUM). This enabled the construction of a series of picomolar mtPTP inhibitors that also potently increase the calcium retention capacity of the mitochondria. Finally, the therapeutic potential and in vivo efficacy of one of the most potent analogues, N-(3-chloro-2-methylphenyl)-5-(4-fluoro-3 hydroxyphenyl)isoxazole-3-carboxamide (60), was validated in a biologically relevant zebrafish model of collagen VI congenital muscular dystrophies. PMID- 26286379 TI - The development, content validity and inter-rater reliability of the SMART-Goal Evaluation Method: A standardised method for evaluating clinical goals. AB - INTRODUCTION: Goal setting is a complex skill. The use of formal goal writing procedures (including the use of the SMART goal model) has been advocated. However, a standardised method of writing and evaluating SMART goals is currently lacking. This study comprised of two phases. The aims of phase one was to (i) develop the SMART Goal Evaluation Method (SMART-GEM) based on a SMART goal model; and (ii) investigate the content validity of the SMART-GEM. The aim of phase two of the study was to test the inter-rater reliability of the SMART-GEM. METHODS: Development of the SMART- GEM involved defining and constructing evaluation criteria suitable for auditing goal statements. A content validity assessment was conducted using an expert panel of Occupational Therapists (n = 10). Inter-rater reliability of the SMART-GEM was examined using a purposive sample of multiple raters (n = 24). RESULTS: The SMART- GEM was rated as having good content validity (individual items CVI ranged from 0.90 to 1.00; total SMART- GEM CVI = 0.99, rho = 0.05). Agreement between raters on individual items ranged from poor (kappa = 0.254) to excellent (kappa = 0.965) and agreement of overall grades was fair to good (kappa = 0.582). Inter-rater agreement on total scores was found to be very good (ICC = 0.895, 95% CI = 0.743 to 0.986, rho = 0.001) with excellent internal consistency (alpha = 0.995). CONCLUSION: The SMART-GEM demonstrated good construct validity and very good inter-rater reliability on total score and shows promise as a standardised method to writing and evaluating clinical goals. PMID- 26286380 TI - Upregulation of HO-1 with Haemin Alleviates LPS-Stimulated Pro-inflammatory Responses Through Downregulation of p38 Signalling Pathways in Rat Liver. AB - Haem oxygenase-1 (HO-1) plays an important role in inflammatory disease development and progression. Whether it has an anti-inflammatory role in lipopolysaccharide (LPS)-induced liver injury remains unclear. To investigate the functional role of HO-1 in protecting liver tissue against inflammatory response stimulated by LPS in rat and the mechanism by which it achieves this protective effect, LPS-stimulated inflammatory models were established. In pretreatment of rats with HO-1 activator (haemin) or inhibitor (zinc protoporphyrin-9, ZnPP, a specific inhibitor of HO) before LPS stimulation, we evaluated the pathological changes by haematoxylin-eosin staining. The mRNA expression and secretion of IL 1beta and IL-6 in rat liver were analysed using the real-time PCR and ELISA. Real time PCR and Western blot were also used to evaluate the expression of HO-1, p38 and p-p38 in liver. Liver CO contents were sensitized to the expression of HO-1. Induction of HO-1 by haemin remarkably inhibited the expression of p38, and addition of ZnPP increased this expression. Our results demonstrate that HO-1 is an anti-inflammation factor in LPS-stimulated liver, which regulate the inflammatory response through downregulation of p38 signalling pathways in rat liver. PMID- 26286381 TI - A Dutch nationwide evaluation of serological assays for detection of Borrelia antibodies in clinically well-defined patients. AB - Numerous tests for the detection of antibodies against Borrelia burgdorferi are commercially available. Manufacturer-derived data invariably report a high sensitivity and specificity, but comparative studies demonstrate large differences in clinical practice, especially with regard to specificity. We retrospectively collected data from validation studies for B. burgdorferi antibody assays from 8 laboratories in the Netherlands. The total number of samples was 809. Samples were selected based on clinical and laboratory parameters. We included samples from patients with erythema migrans, acrodermatitis chronicum atrophicans, and neuroborreliosis; cross-reactivity controls; and healthy controls. Data are presented from 10 enzyme-linked immunosorbent assays and 5 immunoblots. For manifestations of B. burgdorferi infection with short disease duration, the positivity rate of the assays varied significantly. In patients with long disease duration, the positivity rate differed only marginally. In cross-reactivity controls, there was significant variation in the reactivity rate. The majority of false-positive reactions are of the IgM isotype. PMID- 26286382 TI - Advances in photoplethysmography: beyond arterial oxygen saturation. AB - PURPOSE: Photoplethysmography permits continuous measurement of heart rate and peripheral oxygen saturation and has been widely used to inform clinical decisions. Recently, a myriad of noninvasive hemodynamic monitoring devices using this same technology have been increasingly available. This narrative review aims to summarize the principles that form the basis for the function of these devices as well as to comment on trials evaluating their accuracy and clinical application. PRINCIPAL FINDINGS: Advanced monitoring devices extend photoplethysmography technology beyond measuring oxygen concentration and heart rate. Quantification of respiratory variation of the photoplethysmographic waveform reflects respiratory variation of the arterial pressure waveform and can be used to gauge volume responsiveness. Both the volume-clamp and physiocal techniques are extensions of conventional photoplethysmography and permit continuous measurement of finger arterial blood pressure. Finger arterial pressure waveforms can subsequently inform estimations of cardiac output. CONCLUSIONS: Although respiratory variations of the plethysmographic waveform correlate only modestly with the arterial blood pressure waveform, fluid responsiveness can be relatively consistently assessed using both approaches. Continuous blood pressure measurements obtained using the volume-clamp technique may be as accurate as conventional brachial noninvasive blood pressure measurements. Most importantly, clinical comparative effectiveness studies are still needed in order to determine if these technologies can be translated into improvement of relevant patient outcomes. PMID- 26286383 TI - Perioperative outcomes: Are we asking the right questions? PMID- 26286384 TI - Meta-analysis of selective laser trabeculoplasty versus topical medication in the treatment of open-angle glaucoma. AB - BACKGROUND: The aim of this study was to examine possible differences in clinical outcomes between selective laser trabeculoplasty (SLT) and topical medication in the treatment of open-angle glaucoma. METHODS: Pertinent prospective comparative controlled trials comparing SLT with medication were selected through extensive searches of the PubMed, Embase, Web of Science, Chinese Biomedicine Database, and the Cochrane Controlled Trials Register database from their inception up to March 2014. Efficacy estimates were measured by their weighted mean difference (WMD) to calculate the intraocular pressure reduction (IOPR) from baseline to endpoint and by the odds ratio (OR) to determine success rates. RESULTS: Five prospective studies, which met the predefined criteria, were included in the meta-analysis. Four studies were randomized clinical trials and one study was a prospective non randomized clinical trial. There were a total of 492 eyes of 366 patients with open-angle glaucoma. Four studies involving 325 eyes compared SLT with medication in terms of the IOPR. The WMD of the IOPR from the baseline was 0.6 (95 % confidence intervals: -0.24,1.43) when comparing SLT with medication. No statistical heterogeneity was observed between studies (chi2 = 1.30, P = 0.75, I(2) = 0.0 %). All five studies reported success rates, with a pooled OR of 0.84 (95 % confidence intervals: 0.42, 1.68), which was not statistically significant. No statistical heterogeneity was observed between studies (chi2 = 5.98, P = 0.200, I(2) = 33.1 %). Subgroup and sensitivity analysis confirmed the high stability of the meta-analysis results. CONCLUSIONS: Both SLT and topical medication demonstrate similar success rates and effectiveness in lowering intraocular pressure in patients with open-angle glaucoma. PMID- 26286385 TI - Chronic low back pain clinical outcomes present higher associations with the STarT Back Screening Tool than with physiologic measures: a 12-month cohort study. AB - BACKGROUND: Stratification strategies based on identifying patient's prognosis in order to guide patient care constitute one of the most prominent and recent approach in low back pain research. The STarT Back Screening Tool (SBST) although promising, has not been studied in patients with chronic low back pain (cLBP). Considering how challenging it is to translate research into practice, the value of integrating a new tool should be thoroughly assessed. The purpose was therefore to assess associations between the short- and long-terms clinical status and two types of variables, physiologic measures and the SBST, in participants with cLBP. The ability of both types of variables to discriminate between participants with and without higher levels of disability, pain, fear of movement and patient's global impression of change was also investigated. METHODS: Fifty-three volunteers with cLBP participated in an initial evaluation and follow-ups at 2-, 4-, 6- and 12-month. Physiologic measures (maximal voluntary contraction, maximal endurance and muscle activity evaluated during prone and lateral isometric tasks) and the SBST were assessed at baseline. Disability (Oswestry Disability Index, ODI), pain intensity (101-point Numerical Rating Scale, NRS), fear of movement (Tampa Scale for Kinesiophobia, TSK) and patient's global impression of change (7-point scale, PGIC) were evaluated at baseline and at each follow-up. Aside the use of correlation analyses to assess potential associations; ROC curves were performed to evaluate the discriminative ability of physiologic measures and the SBST. RESULTS: The SBST allowed for the identification of participants presenting higher levels of disability (ODI >=24 %), pain (NRS >=37 %) or fear of movement (TSK >=41/68) over a 12-month period (AUC = 0.71 to 0.84, ps < 0.05). The SBST score was also correlated with disability at each follow-up (tau = 0.22 to 0.33, ps < 0.05) and with pain intensity and fear of movement at follow-ups. Among physiologic measures, only maximal voluntary contraction was correlated to disability, pain intensity or fear of movement during the follow-up (|tau| = 0.26 to 0.32, ps < 0.05) and none was able to identify participants presenting higher levels of outcomes (AUC ps > 0.05). CONCLUSION: Physiologic measures obtained during prone and lateral tests have limited associations with the clinical status over a 12-month period in patients with nonspecific chronic low back pain. On the other hand, the STarT Back Screening Tool is useful for the identification of patients who will present higher levels of disability, pain intensity and fear of movement over a year. TRIAL REGISTRATION: Clinicaltrials.gov NCT02226692. PMID- 26286386 TI - Significant Radiation Dose Reduction in the Hybrid Operating Room Using a Novel X ray Imaging Technology. AB - OBJECTIVE/BACKGROUND: To prospectively quantify radiation dose change in aortoiliac endovascular procedures in the hybrid operating room (OR) for patients and medical staff with a novel X-ray imaging technology (ClarityIQ technology), and to assess whether procedure or fluoroscopy time or dose of iodinated contrast was affected. METHODS: A prospective study including 138 patients was performed to compare radiation dose before and after installation of a novel X-ray imaging technology. Endovascular aneurysm repair (EVAR) was performed in 37 patients and an endovascular procedure for aortoiliac occlusive disease (AIOD) in 101. Patient radiation dose in air kerma (AK) and dose area product (DAP), patient demographics, and procedural data were recorded. Staff radiation dose was measured with real time personal dosimetry measurements. In both the EVAR and AIOD groups the reference system, ALX (AlluraXper FD20; Philips Healthcare, Best, the Netherlands), was compared with the upgraded X-ray system, CIQ (AlluraClarity FD20; Philips Healthcare). Procedure time, fluoroscopy time, and iodinated contrast dose were recorded. RESULTS: Patient radiation dose reduction in the EVAR group, in median AK, was 56% (ALX = 1,262.5 mGy; CIQ = 556.0 mGy [p < .01]); and in median DAP it was 57% (ALX = 224.4 Gycm(2) and CIQ = 95.8 Gycm(2) [p < .01]). Patient radiation dose reduction in the AIOD group, in median AK, was 76% (ALX = 1,011.0 mGy; CIQ = 248.0 mGy [p < .01]); and in median DAP it was 73% (ALX = 138.1 Gycm(2); CIQ = 38.0 Gycm(2) [p < .01]). Staff dose reduction in the EVAR group was 16% (ALX = 70.1 MUSv; CIQ = 59.2 MUSv [p = .43]) and in the AIOD group it was 69% (ALX = 96.2 MUSv; CIQ = 30.1 MUSv [p < .01]). There was no statistically significant difference between patient demographics, procedure time, fluoroscopy time, and iodinated contrast medium use in the two treatment groups before and after installation. CONCLUSION: A novel X-ray imaging technology in the hybrid OR suite resulted in a significant reduction of patient and staff radiation dose without affecting procedure length, fluoroscopy time, or use of contrast. PMID- 26286387 TI - Time to Close the Stable Doors Before the Horse Has Bolted. PMID- 26286388 TI - Acute Monocular Blindness after Carotid Endarterectomy due to Non-arteritic Anterior Ischemic Optic Neuropathy. PMID- 26286389 TI - Minireview on current antiangiogenic agents in oncology and ophthalmology. AB - Antiangiogenic drugs are approved for many cancer types for longer than a decade. Furthermore, several antiangiogenic agents are approved for local application in ophthalmology for treatment of macular degeneration, venous retinal occlusion and diabetic retinopathy. Knowing that antiangiogenic agents are active in ocular system, we reviewed the current literature, whether antiangiogenic drugs may cause ocular side effects in cancer patients by systemic application. Furthermore, we searched in published papers, if systemic application of antiangiogenic agents in cancer patients may simultaneously treat their ocular disorders, if they have such. Finally, we emphasized cooperation between an oncologist and ophthalmologist when treating patients with antiangiogenic drugs. PMID- 26286390 TI - Spasticity Health Literacy Among Canadian Family Physicians. PMID- 26286391 TI - Path analyses of cross-sectional and longitudinal data suggest that variability in natural communities of blood-associated parasites is derived from host characteristics and not interspecific interactions. AB - BACKGROUND: The parasite composition of wild host individuals often impacts their behavior and physiology, and the transmission dynamics of pathogenic species thereby determines disease risk in natural communities. Yet, the determinants of parasite composition in natural communities are still obscure. In particular, three fundamental questions remain open: (1) what are the relative roles of host and environmental characteristics compared with direct interactions between parasites in determining the community composition of parasites? (2) do these determinants affect parasites belonging to the same guild and those belonging to different guilds in similar manners? and (3) can cross-sectional and longitudinal analyses work interchangeably in detecting community determinants? Our study was designed to answer these three questions in a natural community of rodents and their fleas, ticks, and two vector-borne bacteria. METHODS: We sampled a natural population of Gerbillus andersoni rodents and their blood-associated parasites on two occasions. By combining path analysis and model selection approaches, we then explored multiple direct and indirect paths that connect (i) the environmental and host-related characteristics to the infection probability of a host by each of the four parasite species, and (ii) the infection probabilities of the four species by each other. RESULTS: Our results suggest that the majority of paths shaping the blood-associated communities are indirect, mostly determined by host characteristics and not by interspecific interactions or environmental conditions. The exact effects of host characteristics on infection probability by a given parasite depend on its life history and on the method of sampling, in which the cross-sectional and longitudinal methods are complementary. CONCLUSIONS: Despite the awareness of the need of ecological investigations into natural host-vector-parasite communities in light of the emergence and re emergence of vector-borne diseases, we lack sampling methods that are both practical and reliable. Here we illustrated how comprehensive patterns can be revealed from observational data by applying path analysis and model selection approaches and combining cross-sectional and longitudinal analyses. By employing this combined approach on blood-associated parasites, we were able to distinguish between direct and indirect effects and to predict the causal relationships between host-related characteristics and the parasite composition over time and space. We concluded that direct interactions within the community play only a minor role in determining community composition relative to host characteristics and the life history of the community members. PMID- 26286393 TI - Caring for a Person With Amnestic Mild Cognitive Impairment. AB - While much of the literature on caregiver burden has focused on caregiving for people living with Alzheimer's disease (AD) there is little information on the experience of caring for a loved one living with amnestic Mild Cognitive Impairment (aMCI), the group most likely to convert to AD. A hermeneutic phenomenological approach was used to understand the organizing principles that give experiences of being form and meaning in the lifeworld. Study findings highlight the precarious nature of caregiver role acquisition and the heterogeneity that is present among informal care providers. Specifically, the findings suggest that the wearing of multiple situational masks is required by the carer to cope with accumulated progressive losses suffered as they continually adjust to their new and evolving carer identity. Support groups specific to the carers of those living with aMCI are needed in an effort to remove these masks and to validate this unique caregiving experience. PMID- 26286392 TI - Measurement of skeletal related events in SEER-Medicare: a comparison of claims based methods. AB - BACKGROUND: Skeletal related events (SREs) are common in men with metastatic prostate cancer (mPC). Various methods have been used to identify SREs from claims data. The objective of this study was to provide a framework for measuring SREs from claims and compare SRE prevalence and cumulative incidence estimates based on alternative approaches in men with mPC. METHODS: Several claims-based approaches for identifying SREs were developed and applied to data for men aged [greater than or equal to] 66 years newly diagnosed with mPC between 2000 and 2009 in the SEER-Medicare datasets and followed through 2010 or until censoring. Post-diagnosis SREs were identified using claims that indicated spinal cord compression (SCC), pathologic fracture (PF), surgery to bone (BS), or radiation (suggestive of bone palliative radiation, RAD). To measure SRE prevalence, two SRE definitions were created: 'base case' (most commonly used in the literature) and 'alternative' in which different claims were used to identify each type of SRE. To measure cumulative incidence, we used the 'base case' definition and applied three periods in which claims were clustered to episodes: 14-, 21-, and 28-day windows. RESULTS: Among 8997 mPC patients, 46 % experienced an SRE according to the 'base case' definition and 43 % patients experienced an SRE according to the 'alternative' definition. Varying the code definition from 'base case' to 'alternative' resulted in an 8 % increase in the overall SRE prevalence. Using the 21-day window, a total of 12,930 SRE episodes were observed during follow up. Varying the window length from 21 to 28 days resulted in an 8 % decrease in SRE cumulative incidence (RAD: 10 %, PF: 8 %, SCC: 6 %, BS: 0.2 %). CONCLUSIONS: SRE prevalence was affected by the codes used, with PF being most impacted. The overall SRE cumulative incidence was affected by the window length used, with RAD being most affected. These results underscore the importance of the baseline definitions used to study claims data when attempting to understand relevant clinical events such as SREs in the real world setting. PMID- 26286394 TI - Strategies for effective goals of care discussions and decision-making: perspectives from a multi-centre survey of Canadian hospital-based healthcare providers. AB - BACKGROUND: Communication gaps impact the quality of patient care. Previous research has focused on communication barriers rather than seeking solutions. Our aim was to identify strategies for effective communication and decision-making about goals of care for medical interventions in serious illness, from the perspectives of hospital-based healthcare providers. METHODS: A cross-sectional survey composed of closed- and open-ended questions about goals of care communication and decision-making was administered to healthcare providers in 13 centres in six Canadian provinces. We analyzed a portion of the open-ended survey questions, specifically (1) suggestions for overcoming barriers encountered in discussing goals of care, and (2) currently effective practices. Thematic content analysis was used to analyze responses to the open-ended questions. RESULTS: Of the 1,256 respondents to the larger survey, 468 responded to the open-ended questions (37%), including 272 of 512 nurses (53%), 153 of 484 internal medicine trainees (32%), and 43 of 260 attending physicians (17%). Responses to each of the two questions were similar, generating a common set of themes and subthemes. Effective strategies and ideas for improving communication and decision-making about goals of care clustered under five themes: patient and family factors, communication between healthcare providers and patients, interprofessional collaboration, education, and resources. Subthemes highlighted core elements of shared decision-making. CONCLUSIONS: Translating our findings into multifaceted interventions that consider patient and family factors, address knowledge gaps, optimize resource utilization, and facilitate communication and collaboration between patients, families and healthcare providers may improve communication and decision-making about goals of care. PMID- 26286395 TI - Modelling of diabetes knowledge, attitudes, self-management, and quality of life: a cross-sectional study with an Australian sample. AB - BACKGROUND: Quality of life (QoL) is an important aspect of wellbeing for people with chronic conditions like type 2 diabetes, making it a noteworthy outcome. Knowledge about diabetes, attitudes, and self-management of diabetes are key factors that might directly or indirectly impact QoL. However, little is known about the inter-relationships between diabetes knowledge, attitudes, self management and QoL among people with type 2 diabetes mellitus (T2DM). The aim of this study was to examine a model describing the relationship between diabetes knowledge, attitudes, self-management, and QoL of people with T2DM that is based on previous research linking pairs of these variables. METHODS: A cross-sectional study design was employed in this research. A total of 291 participants, 192 males and 99 females, with T2DM, whose mean age was 55.8 (standard deviation = 11.09) completed questionnaires measuring diabetes knowledge (Diabetes Knowledge Scale), attitudes (Diabetes Integration Scale -19), self-management (Summary of Diabetes Self-care Activities Scale), including the aspects of diet, exercise, blood glucose testing, and foot care, and QoL (Diabetes Quality of Life Scale), comprising the aspects of satisfaction and impact on QoL respectively. To examine the model we proposed relating these variables, data were analysed using the path analysis. RESULTS: In the final model, diabetes knowledge was a significant predictor for attitudes and self-management in terms of blood glucose testing. Attitudes was a significant predictor for self-management in terms of diet. In addition, self-management in terms of blood glucose testing was a significant predictor of impact of QoL, and self-management in terms of diet was a significant predictor of satisfaction and impact of QoL. Self-management in terms of exercise was a significant predictor of satisfaction in QoL. The final model reflected a good fit (chi(2) (14) = 22.52, p = 0.069; CFI = 0.983; GFI = 0.983; RMSEA = 0.046). CONCLUSIONS: Diabetes knowledge, attitudes, and self-management are important factors that can impact the QoL among people with type 2 diabetes. PMID- 26286396 TI - A Comprehensive Study of Tumor Necrosis Factor-Alpha Genetic Polymorphisms, its Expression in Skin and Relation to Histopathological Features in Psoriasis. AB - BACKGROUND: Tumor necrosis factor-alpha (TNFalpha) is an important inflammatory mediator in psoriasis and several genetic polymorphisms of this cytokine have been reported. Majority of studies have focused on the increased G- A polymorphism at the -308 position in psoriasis. There has been no comprehensive study evaluating the genetic polymorphisms, TNFalpha expression in the skin and histopathology. We are undertaking this study to outline TNFalpha genetic polymorphisms, its skin expression and histopathological correlation to help determine its role at the genetic and protein level. MATERIALS AND METHODS: 112 patients of psoriasis and 243 healthy controls were included in this prospective study. 5 ml of peripheral blood was collected to study the TNFalpha genetic polymorphisms by polymerase chain reaction and restriction fragment length polymorphism analysis. Histopathological analysis of biopsies from the 112 patients were done using visual analogue scale and correlated with the findings. 61 of these cases were analyzed for TNFalpha expression by immunohistochemistry. The results of study were statistically analyzed using SPSS 13.0 statistical package program. RESULTS: A strong association of TNFalpha -308 G/A polymorphism in psoriasis cases was detected. The A allele of the TNFalpha -308 G/A polymorphism occurs rarely in the Indian population, however there is an over representation of this allele in psoriatic patients. There was no association seen between TNFalpha genotype and histopathological severity of psoriasis. CONCLUSION: The study emphasized the central role of TNFalpha in the pathogenesis of psoriasis. TNFalpha genotyping may be helpful in identifying subjects in whom anti-TNFalpha therapeutic strategies may be tried. PMID- 26286397 TI - Peak oxygen uptake and breathing pattern in COPD patients--a four-year longitudinal study. AB - BACKGROUND: Activities of daily living in patients with chronic obstructive pulmonary disease (COPD) are limited by exertional dyspnea and reduced exercise capacity. The aims of the study were to examine longitudinal changes in peak oxygen uptake (VO2peak), peak minute ventilation (VEpeak) and breathing pattern over four years in a group of COPD patients, and to examine potential explanatory variables of change. METHODS: This longitudinal study included 63 COPD patients, aged 44-75 years, with a mean forced expiratory volume in one second (FEV1) at baseline of 51 % of predicted (SD = 14). The patients performed two cardiopulmonary exercise tests (CPETs) on treadmill 4.5 years apart. The relationship between changes in VO2peak and VEpeak and possible explanatory variables, including dynamic lung volumes and inspiratory capacity (IC), were analysed by multivariate linear regression analysis. The breathing pattern in terms of the relationship between minute ventilation (VE) and tidal volume (VT) was described by a quadratic equation, VT = a + b?VE + c?VE (2), for each test. The VTmax was calculated from the individual quadratic relationships, and was the point where the first derivative of the quadratic equation was zero. The mean changes in the curve parameters (CPET2 minus CPET1) and VTmax were analysed by bivariate and multivariate linear regression analyses with age, sex, height, changes in weight, lung function, IC and inspiratory reserve volume as possible explanatory variables. RESULTS: Significant reductions in VO2peak (p < 0.001) and VEpeak (p < 0.001) were related to a decrease in resting IC and in FEV1. Persistent smoking contributed to the reduction in VO2peak. The breathing pattern changed towards a lower VT at a given VE and was related to the reduction in FEV1. CONCLUSION: Increasing static hyperinflation and increasing airway obstruction were related to a reduction in exercise capacity. The breathing pattern changed towards more shallow breathing, and was related to increasing airway obstruction. PMID- 26286398 TI - Characteristics and determinants of knowledge transfer policies at universities and public institutions in medical research--protocol for a systematic review of the qualitative research literature. AB - BACKGROUND: Universities, public institutions, and the transfer of knowledge to the private sector play a major role in the development of medical technologies. The decisions of universities and public institutions regarding the transfer of knowledge impact the accessibility of the final product, making it easier or more difficult for consumers to access these products. In the case of medical research, these products are pharmaceuticals, diagnostics, or medical procedures. The ethical dimension of access to these potentially lifesaving products is apparent and distinguishes the transfer of medical knowledge from the transfer of knowledge in other areas. While the general field of technology transfer from academic and public to private actors is attracting an increasing amount of scholarly attention, the specifications of knowledge transfer in the medical field are not as well explored. This review seeks to provide a systematic overview and analysis of the qualitative literature on the characteristics and determinants of knowledge transfer in medical research and development. METHODS: The review systematically searches the literature for qualitative studies that focus on knowledge transfer characteristics and determinants at medical academic and public research institutions. It aims at identifying and analyzing the literature on the content and context of knowledge transfer policies, decision making processes, and actors at academic and public institutions. The search strategy includes the databases PubMed, Web of Science, ProQuest, and DiVa. These databases will be searched based on pre-specified search terms. The studies selected for inclusion in the review will be critically assessed for their quality utilizing the Qualitative Research Checklist developed by the Clinical Appraisal Skills Programme. Data extraction and synthesis will be based on the meta-ethnographic approach. DISCUSSION: This review seeks to further the understanding of the kinds of transfer pathways that exist in medical knowledge transfer as well as what factors lead to the adoption of one pathway over another. The aim is to provide evidence for political and academic actors designing policies for the translation of medical knowledge and public-private cooperation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015014241 . PMID- 26286400 TI - Anomalous pH Effect of Blue Proteorhodopsin. AB - Proteorhodopsin (PR) is a light-driven proton pump found in marine bacteria, and thousands of PRs are classified into blue-absorbing PR (B-PR; lambdamax ~ 490 nm) and green-absorbing PR (G-PR; lambdamax ~ 525 nm). In this report, we present conversion of B-PR into G-PR using anomalous pH effect. B-PR in LC1-200, marine gamma-proteobacteria, absorbs 497 and 513 nm maximally at pH 7 and 4, respectively, whose pH titration was reversible (pKa = 4.8). When pH was lowered from 4, the lambdamax was further red-shifted (528 nm at pH 2). This is unusual because blue shift occurs by chloride binding in the case of bacteriorhodopsin. Surprisingly, when pH was increased from 2 to 7, the lambdamax of this B-PR was further red-shifted to 540 nm, indicating that green-absorbing PR (PR540) is created only by changing pH. The present study reports the conformational flexibility of microbial rhodopsins, leading to the switch of absorbing color by a simple pH change. PMID- 26286399 TI - New Tris(hydroxypyridinone) Bifunctional Chelators Containing Isothiocyanate Groups Provide a Versatile Platform for Rapid One-Step Labeling and PET Imaging with (68)Ga(3.). AB - Two new bifunctional tris(hydroxypyridinone) (THP) chelators designed specifically for rapid labeling with (68)Ga have been synthesized, each with pendant isothiocyanate groups and three 1,6-dimethyl-3-hydroxypyridin-4-one groups. Both compounds have been conjugated with the primary amine group of a cyclic integrin targeting peptide, RGD. Each conjugate can be radiolabeled and formulated by treatment with generator-produced (68)Ga(3+) in over 95% radiochemical yield under ambient conditions in less than 5 min, with specific activities of 60-80 MBq nmol(-1). Competitive binding assays and in vivo biodistribution in mice bearing U87MG tumors demonstrate that the new (68)Ga(3+) labeled THP peptide conjugates retain affinity for the alphavbeta3 integrin receptor, clear within 1-2 h from circulation, and undergo receptor-mediated tumor uptake in vivo. We conclude that bifunctional THP chelators can be used for simple, efficient labeling of (68)Ga biomolecules under mild conditions suitable for peptides and proteins. PMID- 26286401 TI - Concerted HO2 Elimination from alpha-Aminoalkylperoxyl Free Radicals: Experimental and Theoretical Evidence from the Gas-Phase NH2(*)CHCO2(-) + O2 Reaction. AB - We have investigated the gas-phase reaction of the alpha-aminoacetate (glycyl) radical anion (NH2(*)CHCO2(-)) with O2 using ion trap mass spectrometry, quantum chemistry, and statistical reaction rate theory. This radical is found to undergo a remarkably rapid reaction with O2 to form the hydroperoxyl radical (HO2(*)) and an even-electron imine (NHCHCO2(-)), with experiments and master equation simulations revealing that reaction proceeds at the ion-molecule collision rate. This reaction is facilitated by a low-energy concerted HO2(*) elimination mechanism in the NH2CH(OO(*))CO2(-) peroxyl radical. These findings can explain the widely observed free-radical-mediated oxidation of simple amino acids to amides plus alpha-keto acids (their imine hydrolysis products). This work also suggests that imines will be the main intermediates in the atmospheric oxidation of primary and secondary amines, including amine carbon capture solvents such as 2-aminoethanol (commonly known as monoethanolamine, or MEA), in a process that avoids the ozone-promoting conversion of (*)NO to (*)NO2 commonly encountered in peroxyl radical chemistry. PMID- 26286402 TI - Phase Transitions in Graphite Oxide Solvates at Temperatures Near Ambient. AB - It is demonstrated that solvent-saturated graphite oxide can be considered to be solid solvate, and two phases with distinctly different solvent composition are found near room temperature. Phase transitions between these two solvated phases were observed using synchrotron powder X-ray diffraction and DSC for methanol, ethanol, acetone, and dimethylformamide (DMF) solvents. Solvate A, formed at room temperature, undergoes a reversible phase transition into expanded Solvate L at temperatures slightly below ambient due to insertion of one monolayer of solvent molecules between the GO planes. The phase transition is reversible upon heating, whereas the low-temperature expanded phase L can be quenched to room temperature for ethanol and DMF solvates. PMID- 26286403 TI - p-n Junction at the Interface between Metallic Systems. AB - Density functional theory is used to evaluate the electronic properties in a composite metallic material consisting of two subsystems made of interacting metallic thin films separated by a subnanometer gap. One of the subsystems, M/Pt M/Pt, has a monolayer of metal M over a core of Pt atoms, and the other is Pt-Pt, where the interacting surfaces are made of pure Pt. At equilibrium, this composite material exhibits a potential barrier at the interface, resembling a semiconductor p-n junction. In the gap region of M/Pt-M/Pt, the amount of electrons correlates with the surface layer degree of polarization, which depends on electronegativity and number of unpaired electrons in the external shells. The electron density in the gap, the system work function, and the built-in potential at the interface of the composite system calculated for various metal skins correlate with the degree of reduction of the Pt atoms located at the junction area. PMID- 26286404 TI - Tuning Metal-Organic Frameworks with Open-Metal Sites and Its Origin for Enhancing CO2 Affinity by Metal Substitution. AB - Reducing anthropogenic carbon emission is a problem that requires immediate attention. Metal-organic frameworks (MOFs) have emerged as a promising new materials platform for carbon capture, of which Mg-MOF-74 offers chemospecific affinity toward CO2 because of the open Mg sites. Here we tune the binding affinity of CO2 for M-MOF-74 by metal substitution (M = Mg, Ca, and the first transition metal elements) and show that Ti- and V-MOF-74 can have an enhanced affinity compared to Mg-MOF-74 by 6-9 kJ/mol. Electronic structure calculations suggest that the origin of the major affinity trend is the local electric field effect of the open metal site that stabilizes CO2, but forward donation from the lone-pair electrons of CO2 to the empty d-levels of transition metals as in a weak coordination bond makes Ti and V have an even higher binding strength than Mg, Ca, and Sc. PMID- 26286405 TI - Carbon Dioxide Migration Pathways in Proteins. AB - Some of the most important biological processes, such as carbon fixation, are dependent on protein-gas interactions. The motion of CO2 through the enzyme phosphoenolpyruvate carboxykinase was investigated using extensive all-atom molecular dynamics simulations. Three discrete migration pathways were located, suggesting the protein directs the movement of CO2. The chemical nature of these pathways is discussed, as are their biotechnological ramifications. PMID- 26286406 TI - Femtosecond Photoelectron Imaging of Aligned Polyanions: Probing Molecular Dynamics through the Electron-Anion Coulomb Repulsion. AB - The first time-resolved photoelectron imaging study of a polyanion is presented. Using the alignment induced through resonance excitation, the photoelectron angular distributions can be qualitatively understood in terms of the position of localized excess charges on the molecular skeleton, which influence the photoemission dynamics. Pump-probe experiments are used to demonstrate that the photoelectron angular distribution is also sensitive to molecular dynamics. This is shown here for the rotational dynamics of a polyanion, in which the photoelectron anisotropy tracks the rotational coherence as it dephases. The methodology can in principle be applied to general molecular dynamics in large polyanions, providing a new route to studying ultrafast structural dynamics in complex gas-phase systems. PMID- 26286407 TI - Nanopattering in CeOx/Cu(111): A New Type of Surface Reconstruction and Enhancement of Catalytic Activity. AB - Our results indicate that small amounts of an oxide deposited on a stable metal surface can trigger a massive surface reconstruction under reaction conditions. In low-energy electron microscopy (LEEM) experiments, no reconstruction of Cu(111) is observed after chemisorbing oxygen or after reducing O/Cu(111) in a CO atmosphere. On the other hand, LEEM images taken in situ during the reduction of CeO2/CuO1-x/Cu(111) show a complex nonuniform transformation of the surface morphology. Ceria particles act as nucleation sites for the growth of copper microterraces once CuO1-x is reduced. Can this reconstructed surface be used to enhance the catalytic activity of inverse oxide/metal catalysts? Indeed, CeOx on reconstructed Cu(111) is an extremely active catalyst for the water-gas shift process (CO + H2O -> H2 + CO2), with the Cu microterraces providing very efficient sites for the dissociation of water and subsequent reaction with CO. PMID- 26286408 TI - Observation of Charge Inversion of an Ionic Liquid at the Solid Salt-Liquid Interface by Sum Frequency Generation Spectroscopy. AB - Sum frequency generation (SFG) vibrational spectroscopy of the ionic liquid, 1 butyl-3-methylimidazolium dicyanamide [BMIM][DCA], in contact with two different solid salt surfaces, BaF2(111) single crystal and solid NaCl{100}, are discussed in this Letter. This investigation describes the nature of an ionic liquid (solid) salt interface using SFG, contributing a new understanding to the molecular-level interactions involved in salts, which are conceptually similar compounds (of purely ionic character) but of different physical properties (liquid versus solid at room temperature). Results show the presence of [BMIM](+) at the NaCl{100} surface and [DCA](-) at the BaF2(111) surface. [BMIM](+) cations adhere closely via Coulombic interactions to the negatively charged NaCl{100} surface, while [DCA](-) anions subsequently have a strong electrostatic affinity to the positively charged BaF2(111) surface. Ions of the ionic liquid adsorb to the solid salt surface to form a Helmholtz-like electric double layer. PMID- 26286409 TI - Understanding Periodic Dislocations in 2D Supramolecular Crystals: The PFP/Ag(111) Interface. AB - In-plane dislocation networks arise in both inorganic and organic films as a way of relieving the elastic strain that builds up at the substrate interface. In molecule/surface systems, supramolecular interactions are weak and more complex (compared to the atomic bonds in inorganic films), and their interplay with molecule-substrate interactions is very subtle, making it difficult to single out the driving force for a nanoscale dislocation pattern. On the basis of a combined experimental and theoretical work, we here show that periodic dislocations in a molecular PFP film are mainly driven by the optimization of molecule-substrate interactions. Compared to inorganic networks however, it implies a much lower energy imbalance, allowing a thermally induced transition from a low-energy strain dislocation pattern to a high-energy incommensurate moire. PMID- 26286410 TI - Direct Determination of the Rate Coefficient for the Reaction of OH Radicals with Monoethanol Amine (MEA) from 296 to 510 K. AB - Monoethanol amine (H2NCH2CH2OH, MEA) has been proposed for large-scale use in carbon capture and storage. We present the first absolute, temperature-dependent determination of the rate coefficient for the reaction of OH with MEA using laser flash photolysis for OH generation, monitoring OH removal by laser-induced fluorescence. The room-temperature rate coefficient is determined to be (7.61 +/- 0.76) * 10(-11) cm(3) molecule(-1) s(-1), and the rate coefficient decreases by about 40% by 510 K. The temperature dependence of the rate coefficient is given by k1= (7.73 +/- 0.24) * 10(-11)(T/295)(-(0.79+/-0.11)) cm(3) molecule(-1) s(-1). The high rate coefficient shows that gas-phase processing in the atmosphere will be competitive with uptake onto aerosols. PMID- 26286411 TI - Effects of the Excitation Wavelength on the SERS Spectrum. AB - SERS is nowadays a well-established ultrasensitive technique with potential to solve many analytical problems, especially those related to biosciences. This Perspective article aims at summarizing the experimental complexities, in particular, those related to the interaction of light with the sample, that the SERS practitioner may find when acquiring a spectrum while providing a general basis for the interpretation of the obtained vibrational features. With such an idea in mind, factors related to the instrumentation, the optical enhancer, and the analyte molecule are discussed to illustrate the effects of the incident light on the absolute and relative intensity, as well as the spectral profile of the SERS spectra. PMID- 26286412 TI - Understanding Aqueous Dispersibility of Graphene Oxide and Reduced Graphene Oxide through pKa Measurements. AB - The chemistry underlying the aqueous dispersibility of graphene oxide (GO) and reduced graphene oxide (r-GO) is a key consideration in the design of solution processing techniques for the preparation of processable graphene sheets. Here, we use zeta potential measurements, pH titrations, and infrared spectroscopy to establish the chemistry underlying the aqueous dispersibility of GO and r-GO sheets at different values of pH. We show that r-GO sheets have ionizable groups with a single pK value (8.0) while GO sheets have groups that are more acidic (pK = 4.3), in addition to groups with pK values of 6.6 and 9.0. Infrared spectroscopy has been used to follow the sequence of ionization events. In both GO and r-GO sheets, it is ionization of the carboxylic groups that is primarily responsible for the build up of charge, but on GO sheets, the presence of phenolic and hydroxyl groups in close proximity to the carboxylic groups lowers the pKa value by stabilizing the carboxylate anion, resulting in superior water dispersibility . PMID- 26286413 TI - Templating Highly Crystalline Organic Semiconductors Using Atomic Membranes of Graphene at the Anode/Organic Interface. AB - Charge and energy transport in organic semiconductors is highly anisotropic and dependent on crystalline ordering. Here, we demonstrate a novel approach for ordering crystalline organic semiconductors, with orientations optimized for optoelectronics applications, by using a single monolayer of graphene as a molecular template. We show, in particular, that large-area graphene can be integrated on metals and oxides to modify their surface energies and used to template copper phthalocyanine (CuPc), a prototypical organic semiconductor. On unmodified substrates, thermally evaporated films of CuPc are small-grained, and the molecules are in the "standing-up" (100) orientation. On graphene modified substrates, CuPc is templated in favorable "lying-down" (112) and (012) orientations with drastically larger crystal sizes. This results in an 86% increase in the absorption coefficient at 700 nm and should furthermore result in enhanced energy and charge transport. The use of highly conductive and transparent (>95%) graphene membranes as templates is expected to be a foundation for developing future planar and nanostructured organic light-emitting diodes and organic photovoltaics with improved performance. PMID- 26286414 TI - Ultrafast Spatial Imaging of Charge Dynamics in Heterogeneous Polymer Blends. AB - Proof-of-concept transient absorption microscopy (TAM) with simultaneously high spatial and temporal resolution was demonstrated to image charge generation and recombination in model systems of poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl C61-butyric acid methyl ester (PCBM) blends upon extended thermal annealing. Significant spatial heterogeneity in charge generation and recombination dynamics was revealed on the length scale of hundreds of nanometers near the micrometer sized PCBM crystallites, suggesting that information obtained in ensemble measurements by integrating over microscopically inhomogeneous areas could be misleading. In contrast to previous studies, high sensitivity of our instrumentation allows us to employ low excitation intensities to minimize higher order recombination processes. TAM provides a unique noncontact tool to probe local functionality in microscopically heterogeneous energy harvesting systems. PMID- 26286415 TI - Size Focusing of Nanoparticles by Thermodynamic Control through Ligand Interactions. Molecular Clusters Compared with Nanoparticles of Metals. AB - Ligand-capped metal entities come in two sizes, (1) molecular clusters of 10-200 metal atoms and (2) nanoparticles of 2000-10000 metal atoms. In numerous cases, certain "magic sizes" have been found to be most accessible and stable, clusters of 25, 38, 55, and 102 atoms and nanoparticles of 3500-5000 atoms or 4-5 nm. The most familiar and studied system is that of gold (metal) and thiol (ligand). Herein, the methods of synthesis of these gold clusters versus gold nanoparticles are carefully compared. In the cluster case, an important intermediate is the (Au(+)SR(-))n polymer, which is not the case in the synthesis of nanoparticles either from metal (vapor) atoms or metal ions. Also, it is shown that thiol can act as both a reductant (Au(3+) -> Au(+)) and as an oxidant (Au(0) -> Au(+)). The thermodynamic forces responsible for the favored formation of certain size clusters and nanoparticles are discussed. PMID- 26286416 TI - Trends in the Catalytic Activity of Transition Metals for the Oxygen Reduction Reaction by Lithium. AB - Periodic density functional theory (DFT) calculations indicate that the intrinsic activity of Au, Ag, Pt, Pd, Ir, and Ru for the oxygen reduction reaction by Li (Li-ORR) forms a volcano-like trend with respect to the adsorption energy of oxygen, with Pt and Pd being the most active. The trend is based on two mechanisms: the reduction of molecular O2 on Au and Ag and of atomic O on the remaining metals. Step edges are found to be more active for catalyzing the Li ORR than close-packed surfaces. Our findings identify important considerations in the design of catalyst-promoted air cathodes for nonaqueous Li-air batteries. PMID- 26286417 TI - Interparticle Interactions and Self-Assembly of Functionalized Nanodiamonds. AB - Although unpassivated detonation nanodiamonds are known to form tightly bound (and sometimes ordered) superstructures, in most high performance applications the surface are deliberately functionalized, and this can profoundly alter the aggregation behavior. In the present study, we model the aggregation of functionalized nanodiamonds and show that functionalization greatly reduces the Coulombic interactions characteristic of unsaturated particles. Our results provide new insights into the interactions of functionalized nanoparticles. PMID- 26286418 TI - Ultrafast Photothermal Release of DNA from Gold Nanoparticles. AB - We report results on ultrafast photothermal release of DNA from gold nanoparticles. We show that dehybridization of oligonucleotide duplex anchored on a gold nanoparticle surface occurs during a single laser pulse, leading to the release of single-strand DNA in solution. Breaking of the Au-S bond anchoring the duplex and the release of thiolated DNA are also evidenced. Our findings show that the size distribution of the nanoparticles plays a major role in the control of both phenomena. We establish a criterion regarding the size distribution of nanoparticles that allows full release of DNA without breaking of the anchoring thiol bonds. PMID- 26286419 TI - Gas-Phase Retinal Spectroscopy: Temperature Effects Are But a Mirage. AB - We employ state-of-the-art first-principle approaches to investigate whether temperature effects are responsible for the unusually broad and flat spectrum of protonated Schiff base retinal observed in photodissociation spectroscopy, as has recently been proposed. We first carefully calibrate how to construct a realistic geometrical model of retinal and show that the exchange-correlation M06-2X functional yields an accurate description while the commonly used complete active space self-consistent field method (CASSCF) is not adequate. Using modern multiconfigurational perturbative methods (NEVPT2) to compute the excitations, we then demonstrate that conformations with different orientations of the beta ionone ring are characterized by similar excitations. Moreover, other degrees of freedom identified as active in room-temperature molecular dynamics simulations do not yield the shift required to explain the anomalous spectral shape. Our findings indicate that photodissociation experiments are not representative of the optical spectrum of retinal in the gas phase and call for further experimental characterization of the dissociation spectra. PMID- 26286420 TI - Transforming Anodized WO3 Films into Visible-Light-Active Bi2WO6 Photoelectrodes by Hydrothermal Treatment. AB - We directly transformed anodized tungsten oxide film (WO3.2H2O) into bismuth tungstate (Bi2WO6) by substituting the intercalated water molecules with [Bi2O2](2+) in a hydrothermal treatment. The resultant Bi2WO6 was readily used as an electrode to produce anodic photocurrent in H2 evolution on the Pt counter electrode observed under visible light irradiation. PMID- 26286421 TI - Anomalous Transformation of Vapor-Deposited Highly Stable Glasses of Toluene into Mixed Glassy States by Annealing Above Tg. AB - Vapor-deposited glasses have recently emerged as a remarkable new class of materials that can form much denser and stable glasses than those obtained by cooling the liquid. These new amorphous materials reach lower regions of the energy landscape and may impact important technologies that use vapor-deposition. Here, we report on the formation of a glass with two distinct glassy states obtained through the partial annealing of highly stable vapor-deposited glassy films of toluene. The resulting glass exhibits two clear heat capacity overshoots with different onset and fictive temperatures. The transformation times of the ultrastable glass are around 10(5) times slower than the structural relaxation time (taualpha) of supercooled liquid toluene. We show that the nature of the transformed glass depends on the annealing temperature above Tg. This finding suggests the formation of distinct supercooled liquids at temperatures slightly above Tg during the transformation of the highly stable glass. Our results are compatible with the existence of polyamorphism in toluene. PMID- 26286422 TI - Optical Excitations and Field Enhancement in Short Graphene Nanoribbons. AB - The optical excitations of elongated graphene nanoflakes of finite length are investigated theoretically through quantum chemistry semiempirical approaches. The spectra and the resulting dipole fields are analyzed, accounting in full atomistic details for quantum confinement effects, which are crucial in the nanoscale regime. We find that the optical spectra of these nanostructures are dominated at low energy by excitations with strong intensity, comprised of characteristic coherent combinations of a few single-particle transitions with comparable weight. They give rise to stationary collective oscillations of the photoexcited carrier density extending throughout the flake and to a strong dipole and field enhancement. This behavior is robust with respect to width and length variations, thus ensuring tunability in a large frequency range. The implications for nanoantennas and other nanoplasmonic applications are discussed for realistic geometries. PMID- 26286423 TI - Self-Diffusion of Chain Molecules in the Metal-Organic Framework IRMOF-1: Simulation and Experiment. AB - Metal-organic frameworks (MOFs) possess characteristics, such as tunable pore size and chemical functionality, that make them attractive candidates for separations, catalysis, gas storage, and sensing applications. The rate of diffusion of guest molecules in the pores is an important property for all of these potential applications. In this work, the self-diffusion of hydrocarbons in IRMOF-1 was studied as a function of chain length with a combination of molecular dynamics simulations and pulsed field gradient NMR experiments. Excellent agreement is seen between the experiments and simulations, and the self-diffusion coefficients in IRMOF-1 are on the same order as those in the bulk liquid. Additionally, the effect of concentration on diffusivity was found to be very small for low to moderate loadings. Molecular dynamics simulations also provided insights about the preferential diffusion pathways of these guests in IRMOF-1. PMID- 26286424 TI - Lattice Strain Distributions in Individual Dealloyed Pt-Fe Catalyst Nanoparticles. AB - Lattice strain is considered to play an important role in the oxygen reduction catalysis on Pt-based catalysts. However, so far, direct evidence of the lattice strain in the catalyst nanoparticles has not been achieved. By using aberration corrected high-resolution transmission electron microscopy combined with image simulations, a unique core-shell structure, that is, a percolated lattice contracted Pt-Fe alloy core and a Pt-rich surface with a gradient compressive strain, was directly demonstrated within individual dealloyed Pt-Fe nanoparticles and thus provides direct evidence for the strain effect on their enhanced oxygen reduction activity. PMID- 26286425 TI - Light on the Tip of a Needle: Plasmonic Nanofocusing for Spectroscopy on the Nanoscale. AB - The efficiency of plasmonic nanostructures as optical antennas to concentrate optical fields to the nanoscale has been limited by intrinsically short dephasing times and small absorption cross sections. We discuss a new optical antenna concept based on surface plasmon polariton (SPP) nanofocusing on conical noble metal tips to achieve efficient far- to near-field transformation of light from the micro- to the nanoscale. The spatial separation of the launching of propagating SPPs from their subsequent apex confinement with high energy concentration enables background-free near-field imaging, tip-enhanced Raman scattering, and nonlinear nanospectroscopy. The broad bandwidth and spectral tunability of the nanofocusing mechanism in combination with frequency domain pulse shaping uniquely allow for the spatial confinement of ultrashort laser pulses and few-femtosecond spatiotemporal optical control on the nanoscale. This technique not only extends powerful nonlinear and ultrafast spectroscopies to the nanoscale but can also generate fields of sufficient intensity for electron emission and higher harmonic generation. PMID- 26286426 TI - Interaction of Metals with Suspended Graphene Observed by Transmission Electron Microscopy. AB - In this Perspective, we present an overview of how different metals interface with suspended graphene, providing a closer look into the metal-graphene interaction by employing high-resolution transmission electron microscopy, especially using high-angle dark field imaging. All studied metals favor sites on the omnipresent hydrocarbon surface contamination rather than on the clean graphene surface and present nonuniform distributions, which never result in continuous films but instead in clusters or nanocrystals, indicating a weak interaction between the metal and graphene. This behavior can be altered to some degree by surface pretreatment (hydrogenation) and high-temperature vacuum annealing. Graphene etching is observed in a scanning transmission electron microscope (STEM) under high vacuum and 60 kV electron beam acceleration voltage conditions for all metals, except for Au. This unusual metal-mediated etching sheds new light on the metal-graphene interaction; it might explain the observed higher frequency of cluster nucleation for certain transition metals and might have implications regarding controlled nanomanipulation, that is, for self assembly and sculpturing of future graphene-based devices. PMID- 26286427 TI - Metal at the Nanoscale: Manipulating Matter to Control Light. PMID- 26286428 TI - Protective effect of hydroxyfasudil, a Rho kinase inhibitor, on ventral prostatic hyperplasia in the spontaneously hypertensive rat. AB - BACKGROUND: Rho kinase (ROCK) pathway is associated with various cellular functions, such as smooth muscle contraction, inflammatory response, and cell proliferation. The spontaneously hypertensive rat (SHR) is commonly used genetically hypertensive rat model which develops hyperplastic morphological abnormalities in the ventral prostate. We investigated whether administration of hydroxyfasudil, a ROCK inhibitor, could reduce the levels of growth factors, inflammatory markers, and morphological abnormalities in the ventral prostate of the SHR. METHODS: Twelve-week-old SHRs were treated with hydroxyfasudil (1 mg/kg/day, i.p.) or vehicle once daily for another 6 weeks. Wistar Kyoto (WKY) rats treated with vehicle were used as normotensive controls. At 18 weeks of age, blood pressure and heart rate were measured by the tail cuff method. Then the rats were sacrificed, and the ventral prostates were removed. The levels of ROCK activity, growth factors (TGF-beta1 and bFGF), a smooth muscle differentiation marker (alpha-SMA) and an inflammatory cytokine (IL-6) in the ventral prostate were measured by ELISA and western blot. A histological evaluation in each group was also performed. RESULTS: There were significant increases in blood pressure, prostate weight, prostate body weight ratio, and tissue levels of ROCK activity, TGF-beta1, bFGF, alpha-SMA, and IL-6 in the SHR compared to the WKY rat. Histological examination of the ventral prostate showed morphological abnormalities such as a higher degree of proliferation in the glandular epithelial and stromal area in the SHR compared to the WKY rat. Treatment with hydroxyfasudil reduced the elevated ROCK activity, TGF-beta1, bFGF, alpha-SMA, and IL-6 found in the ventral prostate of the SHR. Moreover, treatment with hydroxyfasudil decreased the morphological abnormalies in the SHR ventral prostate. CONCLUSIONS: Treatment with hydroxyfasudil decreased the growth factors, an inflammatory cytokine, and morphological abnormalies in the SHR ventral prostate. These results suggest that chronic treatment with hydroxyfasudil may inhibit the progression of prostatic hyperplasia in the SHR. PMID- 26286429 TI - Immunohistochemical Detection of Urokinase Plasminogen Activator and Urokinase Plasminogen Activator Receptor in Canine Vascular Endothelial Tumours. AB - Immunohistochemistry was used to assess the expression of urokinase plasminogen activator (uPA) and uPA receptor (uPAR) in 57 canine primary haemangiosarcomas (HSAs), 26 canine cutaneous haemangiomas (HAs) and in control sections of canine cutaneous granulation tissue. The correlation between uPA/uPAR expression and the Ki67 labelling index (LI) was estimated in the HSA and HA tissues. uPA was expressed by 73.2% and 75.0% of splenic HSAs and non-splenic HSAs, respectively. All HSA tissues tested expressed uPAR. Expression of both molecules was significantly higher in HSAs than in cutaneous HAs (3.8% for uPA and 30.7% for uPAR). The average Ki67 LI of the uPA(+)/uPAR(+) HSAs was significantly higher than that of uPA(-)/uPAR(+) HSAs and HA tissues (mean +/- SDs 32.8 +/- 15.3, 15.2 +/- 7.2 and 2.1 +/- 0.7, respectively; P <0.05). These results suggest that uPA and uPAR play a significant role in the malignant proliferation of canine HSA, regardless of the primary origin of the tumour. PMID- 26286430 TI - Effect of Cnidium Lactone on Serum Mutant P53 and BCL-2/BAX Expression in Human Prostate Cancer Cells PC-3 Tumor-Bearing BALB/C Nude Mouse Model. AB - BACKGROUND: Cnidium lactone is a natural coumarin compound that can inhibit a variety of cancer cell proliferation and induce cancer cell apoptosis. This experiment investigated the effect of cnidium lactone on molecular marker expression in prostate cancer nude mice to study its effect in inducing apoptosis. MATERIAL AND METHODS: We randomly and equally divided 30 male BALB/C nude mice inoculated with human prostate cancer cells PC-3 into a negative control group, a cyclophosphamide group (500 mg/Kg), and cnidium lactone groups at 3 doses (280 mg/Kg, 140 mg/Kg, and 70 mg/Kg). The mice were weighed at 2 weeks after administration. Tunnel assay was applied to test the nude mice tumor cell apoptosis. ELISA was performed to detect serum AMACR, CD147, mutant P53, BCL-2, AND BAX expression levels. Tumor tissue was separated and weighed. RESULTS: Mice weight did not change significantly in the groups receiving 3 different doses of cnidium lactone(p>0.05), while it decreased obviously in the cyclophosphamide group (p<0.05). Tumor weight, CD147, mutant P53, and BCL-2 levels were significantly lower in the groups receiving 3 different doses of cnidium lactone than in the negative control group (p<0.05). Among them, the abovementioned indexes decreased markedly in the 280 mg/Kg and 140 mg/Kg dose groups than in the cyclophosphamide group (p<0.05). AMACR and BAX levels showed no significant difference in the cnidium lactone group or the cyclophosphamide group (p>0.05). CONCLUSIONS: Cnidium lactone may induce prostate cancer cell apoptosis and inhibit its proliferation through regulating CD147, mutant P53, and BCL-2 expression in nude mice. PMID- 26286431 TI - Psychosocial Adaptation to Disability Within the Context of Positive Psychology: Philosophical Aspects and Historical Roots. AB - PURPOSE: The purpose of this article is to review the conceptual and clinical similarities that exist between the principles of positive psychology and those underlying rehabilitation counseling and psychology, occupational rehabilitation, and those espoused by the field of psychosocial adaptation to chronic illness and disability (CID). METHODS: Three themes were selected for review. These included the historical contributions of early scholars in the area of psychosocial adaptation to CID that later were indirectly infused into mainstream positive psychology; state and trait constructs that constitute much of the infrastructure of positive psychology and psychosocial adaptation to CID; and, finally, the philosophical congruencies between positive psychology and psychosocial adaptation to CID. CONCLUSION: The existing literature indicates that there is a substantial philosophical and conceptual overlap between the fields of positive psychology and psychosocial adaptation to CID. Since theoreticians and researchers, from both fields, often use differing terminology and definitions to describe similar concepts, as well as seek similar research goals, it would behoove both fields to seek a closer partnership in order to establish a meaningful dialogue that focuses on human strengths and virtues in the lives of people with CID. PMID- 26286432 TI - Demand, Control and Support at Work Among Sick-Listed Patients with Neck or Back Pain: A Prospective Study. AB - Purpose The main aim of this study was to assess changes in perceived demand, control and support at work of neck and back pain patients over 1 year. We also hypothesised that perceived changes in demand, control and support at work were associated with clinical improvement, reduced fear-avoidance beliefs and successful return to work. Methods Four hundred and five sick-listed patients referred to secondary care with neck or back pain were originally included in an interventional study. Of these, two hundred and twenty-six patients reported perceived psychosocial work factors at both baseline and 1-year follow-up, and they were later included in this prospective study. Changes in demand, control and support dimensions were measured by a total of nine variables. Results At the group level, no significant differences were found among the measured subscales. At the individual level, the regression analyses showed that decreases in fear avoidance beliefs about work were consistently related to decreases in demand and increases in control, whereas decreases in disability, anxiety and depression were related to increases in support subscales. Conclusions The perception of demand, control and support appear to be stable over 1 year in patients with neck and back pain, despite marked improvement in pain and disability. Disability, anxiety, depression and fear-avoidance beliefs about work were significantly associated with the perception of the work environment, whereas neck and back pain were not. PMID- 26286433 TI - Rational design of paraoxonase 1 (PON1) for the efficient hydrolysis of organophosphates. AB - A rational design of paraoxonase 1 based on molecular docking discovered H115W/T332S and I74F/H115W/T332S mutants exhibited a 40-fold increase in catalytic efficiency (kcat/Km) toward the hydrolysis of two toxic and popular organophosphates (diethyl-paraoxon and dimethyl-paraoxon). Moreover, the conversion of the paraoxons (741.3-825.6 mg L(-1)) by the evolved mutants was 42 60-fold faster than that by the wild type. PMID- 26286435 TI - Fetal Protection : The Roles of Social Learning and Innate Food Aversions in South India. AB - Pregnancy involves puzzling aversions to nutritious foods. Although studies generally support the hypotheses that such aversions are evolved mechanisms to protect the fetus from toxins and/or pathogens, other factors, such as resource scarcity and psychological distress, have not been investigated as often. In addition, many studies have focused on populations with high-quality diets and low infectious disease burden, conditions that diverge from the putative evolutionary environment favoring fetal protection mechanisms. This study tests the fetal protection, resource scarcity, and psychological distress hypotheses of food aversions in a resource-constrained population with high infectious disease burden. The role of culture is also explored. In the first of two studies in Tamil Nadu, India, we investigated cultural explanations of pregnancy diet among non-pregnant women (N = 54). In the second study, we conducted structured interviews with pregnant women (N = 94) to determine their cravings and aversions, resource scarcity, indices of pathogen exposure, immune activation, psychological distress, and emic causes of aversions. Study 1 found that fruits were the most commonly reported food that pregnant women should avoid because of their harmful effects on infants. Study 2 found modest support for the fetal protection hypothesis for food aversions. It also found that pregnant women most commonly avoided fruits as well as "black" and "hot" foods. Aversions were primarily acquired through learning and focused on protecting the infant from harm. Our findings provide modest support for the fetal protection hypothesis and surprisingly strong support for the influence of cultural norms and learning on dietary aversions in pregnancy. PMID- 26286436 TI - Synthesis and Evaluation of New Generation Cross-Bridged Bifunctional Chelator for (64)Cu Radiotracers. AB - Bifunctional chelators have been successfully used to construct (64)Cu-labeled radiopharmaceuticals. Previously reported chelators with cross-bridged cyclam backbones have various essential features such as high stability of the copper(II) complex, high efficiency of radiolabeling at room temperature, and good biological inertness of the radiolabeled complex, along with rapid body clearance. Here, we report a new generation propylene-cross-bridged chelator with hybrid acetate/phosphonate pendant groups (PCB-TE1A1P) developed with the aim of combining these key properties in a single chelator. The PCB-TE1A1P was synthesized from cyclam with good overall yield. The Cu(II) complex of our chelator showed good robustness in kinetic stability evaluation experiments, such as acidic decomplexation and cyclic voltammetry studies. The Cu(II) complex of PCB-TE1A1P remained intact under highly acidic conditions (12 M HCl, 90 degrees C) for 8 d and showed quasi-reversible reduction/oxidation peaks at -0.77 V in electrochemical studies. PCB-TE1A1P was successfully radiolabeled with (64)Cu ions in an acetate buffer at 60 degrees C within 60 min. The electrophoresis study revealed that the (64)Cu-PCB-TE1A1P complex has net negative charge in aqueous solution. The biodistribution and in vivo stability study profiles of (64)Cu-PCB-TE1A1P indicated that the radioactive complex was stable under physiological conditions and cleared rapidly from the body. A whole body positron emission tomography (PET) imaging study further confirmed high in vivo stability and fast clearance of the complex in mouse models. In conclusion, PCB-TE1A1P has good potential as a bifunctional chelator for (64)Cu-based radiopharmaceuticals, especially those involving peptides. PMID- 26286437 TI - [Diffusion formation and psychiatric diseases]. AB - The basic principle behind diffusion is Brownian motion. The diffusion parameters obtained in a clinical association provide information on the spatial distribution of water molecule mobility and, therefore, evidence of the morphological integrity of the white and grey matters of the brain. In recent years functional magnetic resonance imaging (fMRI) could contribute to obtaining a detailed understanding of the cortical and subcortical cerebral networks. Diffusion tensor imaging (DTI) investigations can demonstrate the extent of anisotropy and the fiber pathways in so-called parametric images. For example, in Alzheimer's disease DTI reveals a reduced structural connectivity between the posterior cingulum and the hippocampus. This article shows examples of the application of diffusion-weighted imaging (DWI) in psychiatric disorders. PMID- 26286434 TI - New data and an old puzzle: the negative association between schizophrenia and rheumatoid arthritis. AB - BACKGROUND: A long-standing epidemiological puzzle is the reduced rate of rheumatoid arthritis (RA) in those with schizophrenia (SZ) and vice versa. Traditional epidemiological approaches to determine if this negative association is underpinned by genetic factors would test for reduced rates of one disorder in relatives of the other, but sufficiently powered data sets are difficult to achieve. The genomics era presents an alternative paradigm for investigating the genetic relationship between two uncommon disorders. METHODS: We use genome-wide common single nucleotide polymorphism (SNP) data from independently collected SZ and RA case-control cohorts to estimate the SNP correlation between the disorders. We test a genotype X environment (GxE) hypothesis for SZ with environment defined as winter- vs summer-born. RESULTS: We estimate a small but significant negative SNP-genetic correlation between SZ and RA (-0.046, s.e. 0.026, P = 0.036). The negative correlation was stronger for the SNP set attributed to coding or regulatory regions (-0.174, s.e. 0.071, P = 0.0075). Our analyses led us to hypothesize a gene-environment interaction for SZ in the form of immune challenge. We used month of birth as a proxy for environmental immune challenge and estimated the genetic correlation between winter-born and non winter born SZ to be significantly less than 1 for coding/regulatory region SNPs (0.56, s.e. 0.14, P = 0.00090). CONCLUSIONS: Our results are consistent with epidemiological observations of a negative relationship between SZ and RA reflecting, at least in part, genetic factors. Results of the month of birth analysis are consistent with pleiotropic effects of genetic variants dependent on environmental context. PMID- 26286438 TI - NBAS mutations cause a multisystem disorder involving bone, connective tissue, liver, immune system, and retina. AB - We report two unrelated patients with a multisystem disease involving liver, eye, immune system, connective tissue, and bone, caused by biallelic mutations in the neuroblastoma amplified sequence (NBAS) gene. Both presented as infants with recurrent episodes triggered by fever with vomiting, dehydration, and elevated transaminases. They had frequent infections, hypogammaglobulinemia, reduced natural killer cells, and the Pelger-Huet anomaly of their granulocytes. Their facial features were similar with a pointed chin and proptosis; loose skin and reduced subcutaneous fat gave them a progeroid appearance. Skeletal features included short stature, slender bones, epiphyseal dysplasia with multiple phalangeal pseudo-epiphyses, and small C1-C2 vertebrae causing cervical instability and myelopathy. Retinal dystrophy and optic atrophy were present in one patient. NBAS is a component of the synthaxin-18 complex and is involved in nonsense-mediated mRNA decay control. Putative loss-of-function mutations in NBAS are already known to cause disease in humans. A specific founder mutation has been associated with short stature, optic nerve atrophy and Pelger-Huet anomaly of granulocytes (SOPH) in the Siberian Yakut population. A more recent report associates NBAS mutations with recurrent acute liver failure in infancy in a group of patients of European descent. Our observations indicate that the phenotypic spectrum of NBAS deficiency is wider than previously known and includes skeletal, hepatic, metabolic, and immunologic aspects. Early recognition of the skeletal phenotype is important for preventive management of cervical instability. PMID- 26286439 TI - Emerging trends and persistent challenges in the management of adult syphilis. AB - There are an estimated 10.6 million incident cases of syphilis worldwide each year. We highlight some persistent challenges and emerging trends in the clinical management of syphilis with a particular focus on therapy, serology, diagnostics, and prevention. Decades after the introduction of penicillin, the optimal management of early syphilis continues to be a controversial topic, particularly in the setting of HIV co-infection. Similarly, the need for routine lumbar puncture in HIV co-infected asymptomatic persons is an unanswered question. Despite advances in both automation and point-of-care diagnostics, we continue to rely on indirect measures of disease activity to manage this infection. As syphilis rates in some populations continue to rise, novel and effective prevention strategies are needed. PMID- 26286441 TI - Reply to Ma et al. PMID- 26286440 TI - Neurocognitive functions and brain atrophy after proven neuroborreliosis: a case control study. AB - BACKGROUND: Patients often report neurocognitive difficulties after neuroborreliosis (NB). The frequency and extent of cognitive problems in European patients have been studied incompletely. METHODS: Sixty patients received a neurological and neuropsychological work-up 6 months or longer after treatment for proven NB. Quality of life, psychiatric symptom load, and brain atrophy were measured. All results were compared with a group of 30 healthy control persons adapted for age, gender and education being serologically negative for Borrelia burgdorferi senso latu. A cognitive sum score and a global sum score including cognitive, psychological results and quality of life data was calculated for both groups. RESULTS: Patients after NB showed a lower (i.e. more impaired) score on the Scripps Neurological rating scale (SNRS), but the observed neurological deficits were generally mild (mean +/- SD: 97.1 +/- 4.7 vs. 99.1 +/- 2.4, p = 0.02). The mean neuropsychological domain results of the NB group were all within the normal range. However, a lower performance was found for the frontal executive function z-values (mean +/- SD -0.29 +/- 0.60 vs. 0.09 +/- 0.60; p = 0.0059) of NB patients. Comparing the global sum score (mean +/- SD 11.3 +/- 4.2 NB vs. 14.3 +/- 2.9 control , p = 0.001) and the cognitive sum score of the NB group with those of the control group (mean +/- SD -0.15 +/- 0.42 NB vs. 0.08 +/- 0.31 control , p = 0.0079), both differences were statistically different. The frequencies of impaired global sum scores and those of the pathological cognitive sum scores (p = 0.07) did not differ statistically. No significant differences were found for health-related quality of life (hrQoL), sleep, psychiatric symptom load, or brain atrophy. CONCLUSION: The mean cognitive functions of patients after proven NB were in the normal range. However, we were able to demonstrate a lower performance for the domain of frontal executive functions, for the mean cognitive sum score and the global sum score as a sign of subtle but measurable sequelae of neuroborreliosis. Brain atrophy is not a common consequence of neuroborreliosis. PMID- 26286442 TI - Tricuspid regurgitation in single ventricular palliation for corrected transposition. PMID- 26286443 TI - The radial artery for coronary artery bypass grafting: a second revival? PMID- 26286445 TI - Study of light-induced MscL gating by EPR spectroscopy. AB - A number of techniques developed to investigate protein structure and function depend on chemically modifying and/or labeling of proteins. However, in the case of homooligomeric proteins, the presence of multiple identical subunits obstructs the introduction of residue-specific labels to only one or several subunits, selectively. Here, in order to study the initial conformational changes of a homopentameric mechanosensitive ion channel during its gating, we developed a method for labeling a defined number of subunits of the channel with two different cysteine-specific compounds simultaneously. The first one is a light sensitive channel activator that determines the degree of openness of the ion channel upon irradiation. The second one is a spin label, containing an unpaired electron, which allows following the resulting structural changes upon channel gating by electron paramagnetic resonance spectroscopy. With this method, we could open MscL into different sub-open states. As the number of light switches per channel increased, the intersubunit spin-spin interactions became less, indicating changes in intersubunit proximities and opening of the channel. The ability of controlled activation of MscL into different open states with a noninvasive trigger and following the resulting conformational changes by spectroscopy will pave the way for detailed spectroscopic studies in the area of mechanosensation. PMID- 26286446 TI - Drowning in Aboriginal and Torres Strait Islander children and adolescents in Queensland (Australia). AB - BACKGROUND: Aboriginal and Torres Strait Islander (Indigenous) children are at greater risk of drowning than other children, however little is known about drowning of Indigenous children. This study identifies the previously unpublished incidence and characteristics of fatal and non-fatal drowning in Indigenous children and adolescents. METHODS: Retrospective data (Jan 2002-Dec 2008) on fatal and non-fatal drowning events among Indigenous and Non-Indigenous Queensland residents aged 0-19 years were obtained from multiple sources across the continuum of care (pre-hospital; emergency department; admitted patients; fatality) and manually linked. Crude incidence rates for fatal and non-fatal events were calculated using population data from the Australian Bureau of Statistics. RESULTS: There were 87 (6.7 % of all events) fatal and non-fatal (combined) Indigenous drowning events yielding a crude Incidence Rate of 16.8/100,000/annum. This is 44 % higher than the incidence rate for Non Indigenous children. For every fatality, nine others were rescued and sought medical treatment (average 12 per year). There were no significant changes in Indigenous drowning incidents over the study period. Drowning rates were higher for Indigenous females than males. Overall incidence was higher among Indigenous children and adolescents than Non-Indigenous children for every calendar year and age-group (0-4 years; 5-9 years; 10-14 years) except those aged 15-19 years where no drowning events were recorded for males. Location of drowning sites was similar in both populations 0-19 years, however there were slight differences in frequency at each of the locations. The three leading drowning locations for Indigenous 0-19 years olds were pool (48 %), bath (21 %) and natural water (16 %), and for non-Indigenous 0-19 years the leading locations were pool (66 %), natural water (13 %) and bath (12 %) (p < .01). Except for pool drowning, Indigenous drowning occurred more often in geographic areas of relative disadvantage. Among Indigenous children drowning location varied with age (p < .001). Most frequent locations by age were: <1 year bath (71 %); 1-4 years pools (80 %); 5-9 years pools (75 %) and 10-19 years beach/ocean (36 %). Severity of event differed statistically with Indigenous status and by remoteness with all fatal drowning events occurring in Regional or Remote areas, and none in Major Cities. CONCLUSIONS: For every fatal drowning among Indigenous children in Queensland aged 0-19 years there are nine non-fatal events. This previously unreported survival ratio of 9:1 indicates the non-fatal injury burden in Indigenous children aged 0-19 years. Although higher Indigenous drowning rates prevailed, no significant changes over time are concerning. Equally the apparent over-representation of Indigenous adolescent females should be weighed against the absence of drowning among Indigenous male adolescents in the same age group in consecutive years of the study. Further investigation around behaviour and culture may highlight protective factors. Culturally specific prevention strategies which take into account social and demographic indicators identified in this study should be delivered to carers and peers of vulnerable age groups who frequent specific locations. Females, swimming ability, supervision and the young are areas which need to be incorporated into Indigenous-specific interventions for drowning prevention. PMID- 26286444 TI - Do Patient- and Parent-reported Outcomes Measures for Children With Congenital Hand Differences Capture WHO-ICF Domains? AB - BACKGROUND: Patient- and parent-reported outcome measures (PROMs) are increasingly used to evaluate the effectiveness of surgery for congenital hand differences (CHDs). Knowledge of an existing outcome measure's ability to assess self-reported health, including psychosocial aspects, can inform the future development and application of PROMs for CHD. However, the extent to which measures used among children with CHD align with common, accepted metrics of self reported disability remains unexplored. QUESTIONS/PURPOSES: We reviewed studies that used PROMs to evaluate surgery for CHD to determine (1) the number of World Health Organization-International Classification of Functioning, Disability and Health (WHO-ICF) domains covered by existing PROMs; (2) the proportion of studies that used PROMs specifically validated among children with CHD; and (3) the proportion of PROMs that targets patients and/or parents. METHODS: We performed a comprehensive review of the literature through a bibliographic search of MEDLINE(r), PubMed, and EMBASE from January 1966 to December 2014 to identify articles related to patient outcomes and surgery for CHD. We evaluated the 42 studies that used PROMs to identify the number and type of WHO-ICF domains captured by existing PROMs for CHD and the proportion of studies that use PROMs validated for use among children with CHD. The most common instruments used to measure patient- and parent-reported outcomes after reconstruction for CHD included the Prosthetic Upper Extremity Functional Index (PUFI), Disabilities of the Arm, Shoulder, and Hand questionnaire, Childhood Experience Questionnaire, and Pediatric Quality of Life Inventory. RESULTS: Current PROMs that have been used for CHD covered a mean of 1.3 WHO-ICF domains (SD +/- 1.3). Only the Child Behavior Checklist and the Piers-Harris Children's Self-Concept Scale captured all ICF domains (body functions and structures, activity, participation, and environmental factors). The PUFI, the only PROM validated specifically for children with congenital longitudinal and transverse deficiency, was used in only four of 42 studies. Only 13 of the 42 studies assessed patient-reported outcomes, whereas five assessed both patient- and parent-reported outcomes. CONCLUSIONS: The PROMs used to assess patients after CHD surgery do not evaluate all WHO-ICF domains (ie, body structure, body function, environmental factors, and activity and participation) and generally are not validated for children with CHD. Given the psychological and sociological aspects of CHD illness, a PROM that encompasses all components of the biopsychosocial model of illness and validated in children with CHD is desirable. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID- 26286447 TI - Expectations and requests regarding team training interventions to promote interdisciplinary collaboration in medical rehabilitation--A qualitative study. AB - BACKGROUND: Interdisciplinary teamwork and team interventions are highly valued in the rehabilitation sector because they can improve outcomes of care for persons with complex health problems. However, little is known about expectations and requests regarding team interventions, especially in medical rehabilitation. This study aimed to explore how clinical managers and health professionals within multidisciplinary rehabilitation teams describe their expectations and requests regarding team-training interventions in the field of medical rehabilitation. METHODS: Considering the methodology of qualitative research, data were collected using semi-structured interviews and focus groups at five rehabilitation clinics in Germany. We conducted face-to-face interviews with 5 clinical managers and 13 department heads of health care teams as well as five focus groups with a total of 35 members of interdisciplinary rehabilitation teams. Afterwards, the data were analyzed through qualitative content analysis encompassing data coding and using inductive thematic analysis. RESULTS: The exploration of team members' and clinical managers' descriptions showed that, to them, interdisciplinary team training programs should include a wide array of training contents. Seven common core themes emerged from the interviews, including participation of employees, leadership, communication, team meetings, team composition, coordination, and equal esteem. Additionally, 13 themes were identified by either managers or team members. The body of expectations regarding team training content in healthcare spans the continuum of changes on the team and organizational levels. On the organizational level, a number of structural factors were mentioned (e.g. improving the general conditions for team meetings, organized workshops to exchange interdisciplinary experiences, and leadership training), and on the team level, changes in procedural factors were listed (e.g. optimizing the consecutive planning and coordination of patient treatments, clarity with regard to roles and responsibilities of team members, and mutual esteem and appreciation between different professions). CONCLUSIONS: The synthesis underscores that there is meaningful heterogeneity in team training needs; training interventions should be locally adapted for each clinic in terms of training content and training strategies. Tailored team interventions are important for rehabilitation clinics. Future work should evaluate employed team training concepts over time as well as training contents, implementation strategies, and learning outcomes. This includes using robust study designs and evaluating team-training effects. PMID- 26286448 TI - HLA-DQB1*05:10, a variant of HLA-DQB1*05:01, detected in a Chinese individual by cloning and sequencing. AB - A novel HLA-DQB1 allele, DQB1*05:10, was detected in a Chinese individual by cloning and sequencing. PMID- 26286449 TI - Effects of Three Types of Exercise Interventions on Healthy Old Adults' Gait Speed: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Habitual walking speed predicts many clinical conditions later in life, but it declines with age. However, which particular exercise intervention can minimize the age-related gait speed loss is unclear. PURPOSE: Our objective was to determine the effects of strength, power, coordination, and multimodal exercise training on healthy old adults' habitual and fast gait speed. METHODS: We performed a computerized systematic literature search in PubMed and Web of Knowledge from January 1984 up to December 2014. Search terms included 'Resistance training', 'power training', 'coordination training', 'multimodal training', and 'gait speed (outcome term). Inclusion criteria were articles available in full text, publication period over past 30 years, human species, journal articles, clinical trials, randomized controlled trials, English as publication language, and subject age >=65 years. The methodological quality of all eligible intervention studies was assessed using the Physiotherapy Evidence Database (PEDro) scale. We computed weighted average standardized mean differences of the intervention-induced adaptations in gait speed using a random effects model and tested for overall and individual intervention effects relative to no-exercise controls. RESULTS: A total of 42 studies (mean PEDro score of 5.0 +/- 1.2) were included in the analyses (2495 healthy old adults; age 74.2 years [64.4-82.7]; body mass 69.9 +/- 4.9 kg, height 1.64 +/- 0.05 m, body mass index 26.4 +/- 1.9 kg/m2, and gait speed 1.22 +/- 0.18 m/s). The search identified only one power training study, therefore the subsequent analyses focused only on the effects of resistance, coordination, and multimodal training on gait speed. The three types of intervention improved gait speed in the three experimental groups combined (n = 1297) by 0.10 m/s (+/-0.12) or 8.4% (+/-9.7), with a large effect size (ES) of 0.84. Resistance (24 studies; n = 613; 0.11 m/s; 9.3%; ES: 0.84), coordination (eight studies, n = 198; 0.09 m/s; 7.6%; ES: 0.76), and multimodal training (19 studies; n = 486; 0.09 m/s; 8.4%, ES: 0.86) increased gait speed statistically and similarly. CONCLUSIONS: Commonly used exercise interventions can functionally and clinically increase habitual and fast gait speed and help slow the loss of gait speed or delay its onset. PMID- 26286450 TI - Personality disorders do not affect treatment outcomes for chronic HCV infection in Spanish prisoners: the Perseo study. AB - BACKGROUND: The link between infection with hepatitis C virus (HCV) and personality disorders (PD) has not been investigated in detail. The aim of this study was to compare the effectiveness of HCV treatment in prisoners with and without PD. METHODS: We performed a prospective multicentre study in inmates from 25 Spanish prisons who had been treated with pegylated interferon alfa-2a plus ribavirin in 2011. PD diagnosis was based on the Personality Diagnostic Questionnaire-4+. We calculated adjusted Odds Ratios (AOR) and 95 % confidence intervals (95 % CI) using logistic regression. RESULTS: The sample included 236 patients (mean age: 40.3 years, 92.8 % male, 79.2 % intravenous drug users, and 26.3 % HIV-coinfected). The prevalence of PD was 72.5 %. 32.2 % of patients discontinued treatment; this percentage was higher in patients with HCV genotypes 1/4 (AOR = 3.55; CI:1.76-7.18) and those without PD (AOR = 2.51; 1.23-5.11). Treatment discontinuation was mainly for penitentiary reasons (40.3 %): release or transfer between prisons. The rate of sustained viral response (SVR) was 52.1 % by ITT and 76.9 % by observed treatment (OT). SVR was higher among patients with genotype 2 or 3, and those with low baseline HCV-RNA. We did not observe any differences between individuals with and without PD in term of SVR, HCV genotype or HIV infection. CONCLUSIONS: Our results support the safety and clinical effectiveness of the treatment of chronic HCV infection in correctional facilities, both in prisoners with PD and those without. Our data support non discrimination between patients with and without PD when offering treatment for HCV infection to prison inmates. TRIAL REGISTRATION: Trial registration number (TRN) NCT01900886 . Date of registration: July 8, 2013. PMID- 26286451 TI - Lace plant ethylene receptors, AmERS1a and AmERS1c, regulate ethylene-induced programmed cell death during leaf morphogenesis. AB - The lace plant, Aponogeton madagascariensis, is an aquatic monocot that forms perforations in its leaves as part of normal leaf development. Perforation formation occurs through developmentally regulated programmed cell death (PCD). The molecular basis of PCD regulation in the lace plant is unknown, however ethylene has been shown to play a significant role. In this study, we examined the role of ethylene receptors during perforation formation. We isolated three lace plant ethylene receptors AmERS1a, AmERS1b and AmERS1c. Using quantitative PCR, we examined their transcript levels at seven stages of leaf development. Through laser-capture microscopy, transcript levels were also determined in cells undergoing PCD and cells not undergoing PCD (NPCD cells). AmERS1a transcript levels were significantly lower in window stage leaves (in which perforation formation and PCD are occurring) as compared to all other leaf developmental stages. AmERS1a and AmERS1c (the most abundant among the three receptors) had the highest transcript levels in mature stage leaves, where PCD is not occurring. Their transcript levels decreased significantly during senescence-associated PCD. AmERS1c had significantly higher transcript levels in NPCD compared to PCD cells. Despite being significantly low in window stage leaves, AmERS1a transcripts were not differentially expressed between PCD and NPCD cells. The results suggested that ethylene receptors negatively regulate ethylene-controlled PCD in the lace plant. A combination of ethylene and receptor levels determines cell fate during perforation formation and leaf senescence. A new model for ethylene emission and receptor expression during lace plant perforation formation and senescence is proposed. PMID- 26286452 TI - BRAF-mutated clear cell sarcoma is sensitive to vemurafenib treatment. AB - We report a patient with a metastatic relapse of clear cell sarcoma, whose tumor harbored BRAF V600E mutation. Standard chemotherapy with doxorubicin and ifosfamide failed to slow the disease progression. Subsequent administration of vemurafenib (960 mg twice a day) resulted in complete tumor response after 8 weeks of treatment. Literature data on the use of vemurafenib and dabrafenib in non-melanoma BRAF-mutated tumors are reviewed. PMID- 26286453 TI - Hyunsoonleella udoensis sp. nov., isolated from a gravel sample from a beach of Udo island, Korea. AB - A Gram-stain negative, non-motile, rod-shaped and aerobic bacterial strain, designated JG48(T), was isolated from a gravel sample taken from a beach adjacent to Udo island, South Korea. Strain JG48(T) was found to grow optimally at 25 degrees C, at pH 7.0-8.0 and in the presence of 2.0 % (w/v) NaCl. The 16S rRNA gene sequence of strain JG48(T) exhibited sequence similarities of 96.67 % to Hyunsoonleella jejuensis CNU004(T). The major fatty acids present in the strain JG48(T) were identified as iso-C15:0, iso-C15:1 G, iso-C17:0 3-OH and iso-C15:0 3 OH. The predominant isoprenoid quinone was identified as MK-6. The polar lipids profile of strain JG48(T) was found to consist of phosphatidylethanolamine, three unidentified amino lipids and four unidentified lipids. The DNA G+C content of strain JG48(T) was determined to be 34 mol%. Based on the morphological and physiological properties, and the results of phylogenetic analyses, the strain is considered to represent a novel species of the genus Hyunsoonleella, for which the name Hyunsoonleella udoensis sp. nov. is proposed. The type strain is JG48(T) (=KCTC 42341(T)=JCM 30600(T)). PMID- 26286454 TI - Genetically modified "obligate" anaerobic Salmonella typhimurium as a therapeutic strategy for neuroblastoma. AB - BACKGROUND: Neuroblastoma currently has poor prognosis, therefore we proposed a new strategy by targeting neuroblastoma with genetically engineered anaerobic Salmonella (Sal-YB1). METHODS: Nude and nonobese diabetic-severe combined immunodeficiency (NOD-SCID) orthotopic mouse models were used, and Sal-YB1 was administered via tail vein. The therapeutic effectiveness, bio-safety, and mechanisms were studied. RESULTS: No mice died of therapy-related complications. Tumor size reduction was 70 and 30% in nude and NOD-SCID mice, respectively. No Salmonella was detected in the urine; 75% mice had positive stool culture if diaminopimelic acid was added, but all turned negative subsequently. Tumor tissues had more Sal-YB1 infiltration, necrosis, and shrinkage in Sal-YB1-treated mice. Significantly higher expression of TLR4, TNF-stimulated gene 6 protein (TSG6), and cleaved caspase 1, 3, 8, and 9 was found in the tumor masses of the Sal-YB1-treated group with a decrease of interleukin 1 receptor-associated kinase (IRAK) and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (IkappaBalpha). There was a high release of TNFalpha both in human macrophages and mouse tumor tissues with Sal-YB1 treatment. The antitumor effect of the supernatant derived from macrophages treated with Sal-YB1 could be reversed with TNFalpha and pan-caspase inhibitors. CONCLUSIONS: This new approach in targeting neuroblastoma by bio-engineered Salmonella with the assistance of macrophages indirectly may have a clinical therapeutic impact in the future. PMID- 26286455 TI - Pivotal role of computers and software in mass spectrometry - SEQUEST and 20 years of tandem MS database searching. AB - Advances in computer technology and software have driven developments in mass spectrometry over the last 50 years. Computers and software have been impactful in three areas: the automation of difficult calculations to aid interpretation, the collection of data and control of instruments, and data interpretation. As the power of computers has grown, so too has the utility and impact on mass spectrometers and their capabilities. This has been particularly evident in the use of tandem mass spectrometry data to search protein and nucleotide sequence databases to identify peptide and protein sequences. This capability has driven the development of many new approaches to study biological systems, including the use of "bottom-up shotgun proteomics" to directly analyze protein mixtures. Graphical Abstract ?. PMID- 26286456 TI - Computer Modeling of an Ion Trap Mass Analyzer, Part I: Low Pressure Regime. AB - We present the multi-particle simulation program suite Computational Ion Trap Analyzer (CITA) designed to calculate the ion trajectories within a Paul quadrupole ion trap developed by the Jet Propulsion Laboratory (JPL). CITA uses an analytical expression of the electrodynamic field, employing up to six terms in multipole expansion and a modified velocity-Verlet method to numerically calculate ion trajectories. The computer code is multithreaded and designed to run on shared-memory architectures. CITA yields near real-time simulations with full propagation of 26 particles per second per core. As a consequence, a realistic numbers of trapped ions (100+ million) can be used and their trajectories modeled, yielding a representative prediction of mass spectrometer analysis of trace gas species. When the model is compared with experimental results conducted at low pressures using the conventional quadrupole and dipole excitation modes, there is an excellent agreement with the observed peak shapes. Owing to the program's efficiency, CITA has been used to explore regions of trapping stability that are of interest to experimental research. These results are expected to facilitate a fast and reliable modeling of ion dynamics in miniature quadrupole ion trap and improve the interpretation of observed mass spectra. Graphical Abstract ?. PMID- 26286458 TI - The Danish approach to forensic age estimation in the living: how, how many and what's new? A review of cases performed in 2012. AB - BACKGROUND: The resulting statement of forensic age estimations in the living is of great consequence for the examinees in question. Concerns have been raised about the nature of these examinations, e.g. the potentially harmful radiographic exposures, as well as the accuracy of the estimated age. AIM: This manuscript investigates the reported age estimates performed at the Section of Forensic Pathology, Institute of Forensic Medicine, Copenhagen, in 2012. SUBJECTS AND METHODS: The results of the individual assessments, i.e. the physical examination, and the radiographic examinations of bone age and dental age, were investigated as well as the correlation between the age estimates of the two latter examinations. RESULTS: In 139 out of the 174 statements, a conclusive chronological age estimate of at least 18 years was given. Although bone age was assessed within the dental age-range in a total of 152 out of 162 cases, some variations in the combined assessments were seen. CONCLUSION: The current procedure is not mathematically or statistically satisfactory. Instead, the most likely age including the variation and error of the age estimate should be reported in statements. The introduction of a Bayesian approach and the use of post-mortem-imaging-based databases may be used for this purpose. PMID- 26286457 TI - Chromosome Y genetic variants: impact in animal models and on human disease. AB - Chromosome Y (chrY) variation has been associated with many complex diseases ranging from cancer to cardiovascular disorders. Functional roles of chrY genes outside of testes are suggested by the fact that they are broadly expressed in many other tissues and correspond to regulators of basic cellular functions (such as transcription, translation, and protein stability). However, the unique genetic properties of chrY (including the lack of meiotic crossover and the presence of numerous highly repetitive sequences) have made the identification of causal variants very difficult. Despite the prior lack of reliable sequences and/or data on genetic polymorphisms, earlier studies with animal chrY consomic strains have made it possible to narrow down the phenotypic contributions of chrY. Some of the evidence so far indicates that chrY gene variants associate with regulatory changes in the expression of other autosomal genes, in part via epigenetic effects. In humans, a limited number of studies have shown associations between chrY haplotypes and disease traits. However, recent sequencing efforts have made it possible to greatly increase the identification of genetic variants on chrY, which promises that future association of chrY with disease traits will be further refined. Continuing studies (both in humans and in animal models) will be critical to help explain the many sex-biased disease states in human that are contributed to not only by the classical sex steroid hormones, but also by chrY genetics. PMID- 26286460 TI - Discovery of Bivalent Kinase Inhibitors via Enzyme-Templated Fragment Elaboration. AB - We have employed novel fragment-based screening methodology to discover bivalent kinase inhibitors with improved selectivity. Starting from a low molecular weight promiscuous kinase inhibitor, we appended a thiol for subsequent reaction with a library of acrylamide electrophiles. Enzyme-templated screening was performed to identify acrylamides that assemble into bivalent inhibitors of c-Src kinase. Upon identification of acrylamide fragments that improve the binding affinity of our lead thiol, we characterized the resulting bivalent inhibitors and identified a series of kinase inhibitors with improved potency and selectivity compared to the thiol-containing precursor. Provided that protein can be prepared free of endogenous reactive cysteines, our methodology is general and could be applied to nearly any enzyme of interest. PMID- 26286461 TI - Zinc as a micronutrient and its preventive role of oxidative damage in cells. AB - Zinc is an essential trace element with special importance in the immune system. Deficiencies of zinc are seen in the course of ageing and in various diseases, such as diabetes mellitus or rheumathoid arthritis. The trace element is essential for a variety of basic cellular functions and especially important for various enzymes participating in the production and neutralization of reactive oxygen species (ROS) which are normally produced by the cell. Under normal conditions ROS are neutralized and are not able to harm the cell, but in case of ROS elevation, oxidative damage within the cell is the result. Interestingly, zinc deficiency is directly associated with oxidative stress. Thus, control and regulation of the intracellular zinc content is essential with participation of various transporter and zinc-binding proteins, such as metallothionein. Oxidative stress is mainly caused by elevated ROS production and a decrease of antioxidant mechanisms. Zinc partly functions as an antioxidant although it is redox inert. Zinc supplementation is associated with decreased ROS formation exhibiting beneficial effects especially in ageing and diabetes mellitus. This review summarizes current findings concerning zinc as a micronutrient and its actions as a pro-antioxidant, and the association between zinc and oxidative stress under various conditions is highlighted. PMID- 26286459 TI - Growth and hormone profiling in children with congenital melanocytic naevi. AB - BACKGROUND: Multiple congenital melanocytic naevi (CMN) is a rare mosaic RASopathy, caused by postzygotic activating mutations in NRAS. Growth and hormonal disturbances are described in germline RASopathies, but growth and hormone status have not previously been investigated in individuals with CMN. OBJECTIVES: To explore premature thelarche, undescended testes, and a clinically abnormal fat distribution with CMN through prospective endocrinological assessment of a cohort of subjects with CMN, and a retrospective review of longitudinal growth of a larger group of patients with CMN from outpatient clinics (which included all subjects in the endocrinological assessment group). PATIENTS AND METHODS: Longitudinal growth in a cohort of 202 patients with single or multiple CMN was compared with the U.K. National Child Measurement Programme 2010. Forty-seven children had hormonal profiling including measurement of circulating luteinizing hormone, follicle-stimulating hormone, thyroid stimulating hormone, adrenocorticotrophic hormone, growth hormone, prolactin, pro opiomelanocortin, estradiol, testosterone, cortisol, thyroxine, insulin-like growth factor-1 and leptin; 10 had oral glucose tolerance testing 25 had dual energy X-ray absorptiometry scans for body composition. RESULTS: Body mass index increased markedly with age (coefficient 0.119, SE 0.016 standard deviation scores per year), at twice the rate of the U.K. population, due to increased adiposity. Three per cent of girls had premature thelarche variant and 6% of boys had persistent undescended testes. Both fat and muscle mass were reduced in areas underlying large naevi, resulting in limb asymmetry and abnormal truncal fat distribution. Anterior pituitary hormone profiling revealed subtle and variable abnormalities. Oral glucose tolerance tests revealed moderate-severe insulin insensitivity in five of 10, and impaired glucose tolerance in one. CONCLUSIONS: Interpersonal variation may reflect the mosaic nature of this disease and patients should be considered individually. Postnatal weight gain is potentially related to the underlying genetic defect; however, environmental reasons cannot be excluded. Naevus-related reduction of fat and muscle mass suggests local hormonal or metabolic effects on development or growth of adjacent tissues, or mosaic involvement of these tissues at the genetic level. Premature thelarche and undescended testes should be looked for, and investigated, as for any child. PMID- 26286462 TI - Familial cleidocranial dysplasia misdiagnosed as rickets over three generations. AB - Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal dysplasia characterized by hypoplastic clavicles, late closure of the fontanels, dental problems and other skeletal features. CCD is caused by mutations, deletions or duplications in runt-related transcription factor 2 (RUNX2), which encodes for a protein essential for osteoblast differentiation and chondrocyte maturation. We describe three familial cases of CCD, misdiagnosed as rickets over three generations. No mutations were detected on standard DNA sequencing of RUNX2, but a novel deletion was identified on quantitative polymerase chain reaction (qPCR) and multiple ligation-dependent probe amplification (MLPA). The present cases indicate that CCD could be misdiagnosed as rickets, leading to inappropriate treatment, and confirm that mutations in RUNX2 are not able to be identified on standard DNA sequencing in all CCD patients, but can be identified on qPCR and MLPA. PMID- 26286464 TI - Lysosomal Acid Lipase Activity: A Tool for the Detection and Management of Fatty Liver Disease? PMID- 26286465 TI - The High Ferritin App: electronic referral to the Australian Red Cross Blood Service for therapeutic venesection. PMID- 26286463 TI - Genome-wide association study of reproductive traits in Nellore heifers using Bayesian inference. AB - BACKGROUND: An important goal of Zebu breeding programs is to improve reproductive performance. A major problem faced with the genetic improvement of reproductive traits is that recording the time for an animal to reach sexual maturity is costly. Another issue is that accurate estimates of breeding values are obtained only a long time after the young bulls have gone through selection. An alternative to overcome these problems is to use traits that are indicators of the reproductive efficiency of the herd and are easier to measure, such as age at first calving. Another problem is that heifers that have conceived once may fail to conceive in the next breeding season, which increases production costs. Thus, increasing heifer's rebreeding rates should improve the economic efficiency of the herd. Response to selection for these traits tends to be slow, since they have a low heritability and phenotypic information is provided only later in the life of the animal. Genome-wide association studies (GWAS) are useful to investigate the genetic mechanisms that underlie these traits by identifying the genes and metabolic pathways involved. RESULTS: Data from 1853 females belonging to the Agricultural Jacarezinho LTDA were used. Genotyping was performed using the BovineHD BeadChip (777 962 single nucleotide polymorphisms (SNPs)) according to the protocol of Illumina - Infinium Assay II (r) Multi-Sample HiScan with the unit SQ TM System. After quality control, 305 348 SNPs were used for GWAS. Forty two and 19 SNPs had a Bayes factor greater than 150 for heifer rebreeding and age at first calving, respectively. All significant SNPs for age at first calving were significant for heifer rebreeding. These 42 SNPs were next or within 35 genes that were distributed over 18 chromosomes and comprised 27 protein-encoding genes, six pseudogenes and two miscellaneous noncoding RNAs. CONCLUSIONS: The use of Bayes factor to determine the significance of SNPs allowed us to identify two sets of 42 and 19 significant SNPs for heifer rebreeding and age at first calving, respectively, which explain 11.35 % and 6.42 % of their phenotypic variance, respectively. These SNPs provide relevant information to help elucidate which genes affect these traits. PMID- 26286467 TI - "Lifting the carpet" on cheating in medical school exams. PMID- 26286466 TI - Analgesic effect of a broad-spectrum dihydropyridine inhibitor of voltage-gated calcium channels. AB - Voltage-activated calcium channels are important facilitators of nociceptive transmission in the primary afferent pathway. Consequently, molecules that block these channels are of potential use as pain therapeutics. Our group has recently reported on the identification of a novel class of dihydropyridines (DHPs) that included compounds with preferential selectivity for T-type over L-type channels. Among those compounds, M4 was found to be an equipotent inhibitor of both Cav1.2 L- and Cav3.2 T-type calcium channels. Here, we have further characterized the effects of this compound on other types of calcium channels and examined its analgesic effect when delivered either spinally (i.t.) or systemically (i.p.) to mice. Both delivery routes resulted in antinociception in a model of acute pain. Furthermore, M4 was able to reverse mechanical hyperalgesia produced by nerve injury when delivered intrathecally. M4 retained partial activity when delivered to Cav3.2 null mice, indicating that this compound acts on multiple targets. Additional whole-cell patch clamp experiments in transfected tsA-201 cells revealed that M4 also effectively blocks Cav3.3 (T-type) and Cav2.2 (N-type) currents. Altogether, our data indicate that broad-spectrum inhibition of multiple calcium channel subtypes can lead to potent analgesia in rodents. PMID- 26286468 TI - Ten-year helium anomaly prior to the 2014 Mt Ontake eruption. AB - Mt Ontake in central Japan suddenly erupted on 27(th) September 2014, killing 57 people with 6 still missing. It was a hydro-volcanic eruption and new magmatic material was not detected. There were no precursor signals such as seismicity and edifice inflation. It is difficult to predict hydro-volcanic eruptions because they are local phenomena that only affect a limited area surrounding the explosive vent. Here we report a long-term helium anomaly measured in hot springs close to the central cone. Helium-3 is the most sensitive tracer of magmatic volatiles. We have conducted spatial surveys around the volcano at once per few years since November 1981. The (3)He/(4)He ratios of the closest site to the cone stayed constant until June 2000 and increased significantly from June 2003 to November 2014, while those of distant sites showed no valuable change. These observations suggest a recent re-activation of Mt Ontake and that helium-3 enhancement may have been a precursor of the 2014 eruption. We show that the eruption was ultimately caused by the increased input of magmatic volatiles over a ten-year period which resulted in the slow pressurization of the volcanic conduit leading to the hydro-volcanic event in September 2014. PMID- 26286469 TI - Effect on Baby-Friendly Hospital Steps When Hospitals Implement a Policy to Pay for Infant Formula. AB - BACKGROUND: The Baby-Friendly Hospital Initiative requires hospitals to pay market price for infant formula. No studies have specifically examined the effect of hospitals paying for infant formula on breastfeeding mothers' exposure to Baby Friendly steps. OBJECTIVES: To investigate the effect of hospitals implementing a policy of paying for infant formula on new mothers' exposure to Baby-Friendly steps and examine the effect of exposure to Baby-Friendly steps on breastfeeding rates. METHODS: We used a repeated prospective cohort study design. We recruited 2 cohorts of breastfeeding mother-infant pairs (n = 2470) in the immediate postnatal period from 4 Hong Kong public hospitals and followed them by telephone up to 12 months postpartum. We assessed participants' exposure to 6 Baby-Friendly steps by extracting data from the medical record and by maternal self-report. RESULTS: After hospitals began paying for infant formula, new mothers were more likely to experience 4 out of 6 Baby-Friendly steps. Breastfeeding initiation within the first hour increased from 28.7% to 45%, and in-hospital exclusive breastfeeding rates increased from 17.9% to 41.4%. The proportion of mothers who experienced all 6 Baby-Friendly steps increased from 4.8% to 20.5%. The risk of weaning was progressively higher among participants experiencing fewer Baby Friendly steps. Each additional step experienced by new mothers decreased the risk of breastfeeding cessation by 8% (hazard ratio = 0.92; 95% CI, 0.89-0.95). CONCLUSION: After implementing a policy of paying for infant formula, breastfeeding mothers were exposed to more Baby-Friendly steps, and exposure to more steps was significantly associated with a lower risk of breastfeeding cessation. PMID- 26286470 TI - A Case Study of Michigan's Breastfeeding Initiative: The Role of Coalitions in Community-Based Breastfeeding Support. AB - The Michigan Department of Community Health (MDCH) funded 9 local breastfeeding coalitions to implement breastfeeding support groups and to develop breastfeeding resources for mothers and health professionals. The authors conducted qualitative analyses of reports, success stories, and MDCH grantees' interview responses (via follow-up call with 3 coalitions) to assess key barriers, facilitators, and lessons learned for coalitions implementing breastfeeding support groups. Coalitions noted implementation barriers related to their organizational structure and to recruiting mothers and finding meeting locations. Facilitators to implementing breastfeeding support groups included referrals, expertise, resources, and incentives. The following themes emerged from the reports analysis regarding how to implement breastfeeding support groups: "meet moms where they are," build community partnerships, and leverage in-kind and financial resources to sustain breastfeeding support groups. PMID- 26286472 TI - Do not assume that no news is good news: test result management and communication in primary care. PMID- 26286471 TI - Changes in apoptotic microRNA and mRNA expression profiling in Caenorhabditis elegans during the Shenzhou-8 mission. AB - Radiation and microgravity exposure have been proven to induce abnormal apoptosis in microRNA (miRNA) and mRNA expression, but whether space conditions, including radiation and microgravity, activate miRNAs to regulate the apoptosis is undetermined. For that purpose, we investigated miRNome and mRNA expression in the ced-1 Caenorhabditis elegans mutant vs the wild-type, both of which underwent spaceflight, spaceflight 1g-centrifuge control and ground control conditions during the Shenzhou-8 mission. Results showed that no morphological changes in the worms were detected, but differential miRNA expression increased from 43 (ground control condition) to 57 and 91 in spaceflight and spaceflight control conditions, respectively. Microgravity altered miRNA expression profiling by decreasing the number and significance of differentially expressed miRNA compared with 1 g incubation during spaceflight. Alterations in the miRNAs were involved in alterations in apoptosis, neurogenesis larval development, ATP metabolism and GTPase-mediated signal transduction. Among these, 17 altered miRNAs potentially involved in apoptosis were screened and showed obviously different expression signatures between space conditions. By integrated analysis of miRNA and mRNA, miR-797 and miR-81 may be involved in apoptosis by targeting the genes ced-10 and both drp-1 and hsp-1, respectively. Compared with ground condition, space conditions regulated apoptosis though a different manner on transcription, by altering expression of seven core apoptotic genes in spaceflight condition, and eight in spaceflight control condition. Results indicate that, miRNA of Caenorhabditis elegans probably regulates apoptotic gene expression in response to space environmental stress, and shows different behavior under microgravity condition compared with 1 g condition in the presence of space radiation. PMID- 26286473 TI - Laboratory testing in general practice: a patient safety blind spot. PMID- 26286474 TI - Sphingomonas hylomeconis sp. nov., isolated from the stem of Hylomecon japonica. AB - A yellow-pigmented bacterium, designated strain GZJT-2T, was isolated from the stem of Hylomecon japonica (Thunb.) Prantl et Kundig collected from Taibai Mountain in Shaanxi Province, north-west China. Cells of strain GZJT-2T were Gram reaction-negative, strictly aerobic, rod-shaped, non-spore-forming and non motile. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain GZJT-2T was a member of the genus Sphingomonas, with sequence similarities of 92.1-96.9 % to type strains of recognized species of the genus Sphingomonas (92.1 % to Sphingomonas oligoaromativorans SY-6T and 96.9 % to Sphingomonas oligophenolica JCM 12082T). Strain GZJT-2T contained ubiquinone-10 (Q-10) as the predominant respiratory quinone and sym-homospermidine as the major polyamine. The major cellular fatty acids were summed feature 8 (comprising C18 : 1omega7c and/or C18 : 1omega6c), summed feature 3 (comprising C16 : 1omega7c and/or C16 : 1omega6c), C16 : 0 and C14 : 0 2-OH. Phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, phosphatidylcholine, sphingoglycolipid, four unidentified phospholipids, an unidentified aminolipid and four unidentified lipids were detected in the polar lipid profile. The DNA G+C content was 62.5 +/- 0.3 mol%. On the basis of data from phenotypic, phylogenetic and DNA-DNA relatedness studies, strain GZJT-2T is considered to represent a novel species of the genus Sphingomonas, for which the name Sphingomonas hylomeconis sp. nov. is proposed. The type strain is GZJT-2T ( = CCTCC AB 2013304T = KCTC 42739T). PMID- 26286475 TI - Cell Death Identification in Anticancer Therapy-Response. PMID- 26286476 TI - Correction: Long Noncoding RNA GAPLINC Regulates CD44-Dependent Cell Invasiveness and Associates with Poor Prognosis of Gastric Cancer. PMID- 26286477 TI - Correction: Host Immune Defense Peptide LL-37 Activates Caspase-Independent Apoptosis and Suppresses Colon Cancer. PMID- 26286478 TI - Cell Death Identification in Anticancer Therapy-Letter. PMID- 26286479 TI - Local atomic structure modulations activate metal oxide as electrocatalyst for hydrogen evolution in acidic water. AB - Modifications of local structure at atomic level could precisely and effectively tune the capacity of materials, enabling enhancement in the catalytic activity. Here we modulate the local atomic structure of a classical but inert transition metal oxide, tungsten trioxide, to be an efficient electrocatalyst for hydrogen evolution in acidic water, which has shown promise as an alternative to platinum. Structural analyses and theoretical calculations together indicate that the origin of the enhanced activity could be attributed to the tailored electronic structure by means of the local atomic structure modulations. We anticipate that suitable structure modulations might be applied on other transition metal oxides to meet the optimal thermodynamic and kinetic requirements, which may pave the way to unlock the potential of other promising candidates as cost-effective electrocatalysts for hydrogen evolution in industry. PMID- 26286480 TI - Capsule Commentary on Binswanger et al., Overdose Education and Naloxone for Patients Prescribed Opioids in Primary Care: A Qualitative Study of Primary Care Staff. PMID- 26286481 TI - Is raloxifene associated with lower risk of mortality in postmenopausal women with vertebral fractures after vertebroplasty?: a hospital-based analysis. AB - BACKGROUND: Osteoporotic fractures are associated with mortality in postmenopausal woman. Whether raloxifen treatment after vertebroplasty can reduce mortality is unclear in this group. To compare the effect of raloxifene and no osteoporosis treatment on the risk of mortality after vertebroplasty, we designed this study. METHODS: This was a retrospective study (January 2001 to December 2007). Follow-up for each participant was calculated as the time from inclusion in the study to the time of death, or to December 31(st), 2013, whichever occurred first. All of the patients underwent baseline bone density studies, and age and body mass index (kg/m(2)) were recorded. All associated medical diseases such as diabetes, hypertension, and liver and renal disease were recorded. RESULTS: One hundred and forty-nine patients with vertebral fractures were enrolled, of whom 51 used raloxifene and 98 patients did not receive any anti osteoporotic therapy. At the end of the follow-up period, 62 patients had died and 87 were still alive. The treated patients had a lower mortality rate than those who did not receive treatment (P = 0.001, HR = 3.845, 95% CI 1.884-7.845). The most common cause of mortality was sepsis, and those who received raloxifene had a lower rate of sepsis compared to those who did not receive treatment (P < 0.001). CONCLUSIONS: Effective treatment with raloxifene may had a lower mortality rate in patients with postmenopausal osteoporosis-related vertebral fractures after vertebroplasty. PMID- 26286482 TI - Cladosporium keratitis - a case report and literature review. AB - BACKGROUND: Fungal keratitis is one of the major causes of infectious keratitis in tropical countries. Symptoms of fungal keratitis consist of blurred vision, redness, tearing, photophobia, pain and foreign body sensation. If not treated effectively, it could lead to blindness. Common causes include Candida spp., Fusarium spp. and Aspergillus spp.. With the limited choices of topical antifungal agents, we were faced with Cladosporium keratitis, a rare cause of fungal keratitis. CASE PRESENTATION: A 62-year-old Asian male construction worker came to us with intense ocular pain, injection of the conjunctiva, blurred vision, and foreign body sensation in his left eye. His visual acuity was 20/40 OD and 20/400 OS. Slit-lamp exam revealed a corneal ulcer with feathery margin and Descemet's membrane folding. The culture yielded Cladosporium species.. The patient did not show improvements after applying topical natamycin (5 %), topical amphotericin B (1mg/ml), topical fluconazole (2mg/ml) and oral ketoconazole (200mg). After shifting the medical regimen to voriconazole via topical and systemic routes (1mg/ml and 200mg respectively), the keratitis was controlled. CONCLUSIONS: Fungal keratitis remains a challenge for ophthalmologists as there is no evidence suggesting any particular drug or combination of drugs is more effective than another. A review of common topical antifungal agents was done. Voriconazole could be a good choice for treating corneal infection by Cladosporium species. PMID- 26286483 TI - Fluorescence microscopy of Streptomyces conjugation suggests DNA-transfer at the lateral walls and reveals the spreading of the plasmid in the recipient mycelium. AB - Conjugative DNA-transfer in mycelial streptomycetes is a unique process, manifested on agar plates by the formation of circular growth retardation zones called pocks. Because pock size correlates with the extent of the transconjugant zone, it was suggested that pocks reflect the spreading of the transferred plasmid in the recipient mycelium. However, this concept has not been experimentally proven yet. The use of an eGFP-encoding derivative of the conjugative pIJ303 plasmid and Streptomyces lividans T7-mCherry as recipient enabled us to differentiate donor, recipient and transconjugant hyphae in mating experiments by fluorescence microscopy. Microscopic observation of the conjugation process suggested DNA-transfer via the lateral walls. At the contact sites mCherry was never observed in the donor, indicating that the conjugative DNA-transfer does not involve interfusion of cytoplasms of donor and recipient. The spreading of the transferred plasmid to the older parts of the recipient mycelium was demonstrated. This spreading was impaired when plasmid-encoded spd genes were inactivated. Deletion of the FtsK-like DNA-translocase encoding tra gene from the plasmid and mating experiments with strains containing chromosomal copies of tra either in the donor and/or in the recipient revealed that Tra had an essential role in intramycelial plasmid spreading. PMID- 26286485 TI - Generation of entanglement in quantum parametric oscillators using phase control. AB - The control of quantum entanglement in systems in contact with environment plays an important role in information processing, cryptography and quantum computing. However, interactions with the environment, even when very weak, entail decoherence in the system with consequent loss of entanglement. Here we consider a system of two coupled oscillators in contact with a common heat bath and with a time dependent oscillation frequency. The possibility to control the entanglement of the oscillators by means of an external sinusoidal perturbation applied to the oscillation frequency has been theoretically explored. We demonstrate that the oscillators become entangled exactly in the region where the classical counterpart is unstable, otherwise when the classical system is stable, entanglement is not possible. Therefore, we can control the entanglement swapping from stable to unstable regions by adjusting amplitude and phase of our external controller. We also show that the entanglement rate is approximately proportional to the real part of the Floquet coefficient of the classical counterpart of the oscillators. Our results have the intriguing peculiarity of manipulating quantum information operating on a classical system. PMID- 26286484 TI - Spatial distribution of Glossina sp. and Trypanosoma sp. in south-western Ethiopia. AB - BACKGROUND: Accurate information on the distribution of the tsetse fly is of paramount importance to better control animal trypanosomosis. Entomological and parasitological surveys were conducted in the tsetse belt of south-western Ethiopia to describe the prevalence of trypanosomosis (PoT), the abundance of tsetse flies (AT) and to evaluate the association with potential risk factors. METHODS: The study was conducted between 2009 and 2012. The parasitological survey data were analysed by a random effects logistic regression model, whereas the entomological survey data were analysed by a Poisson regression model. The percentage of animals with trypanosomosis was regressed on the tsetse fly count using a random effects logistic regression model. RESULTS: The following six risk factors were evaluated for PoT (i) altitude: significant and inverse correlation with trypanosomosis, (ii) annual variation of PoT: no significant difference between years, (iii) regional state: compared to Benishangul-Gumuz (18.0%), the three remaining regional states showed significantly lower PoT, (iv) river system: the PoT differed significantly between the river systems, (iv) sex: male animals (11.0%) were more affected than females (9.0%), and finally (vi) age at sampling: no difference between the considered classes. Observed trypanosome species were T. congolense (76.0%), T. vivax (18.1%), T. b. brucei (3.6%), and mixed T. congolense/vivax (2.4%). The first four risk factors listed above were also evaluated for AT, and all have a significant effect on AT. In the multivariable model only altitude was retained with AT decreasing with increasing altitude. Four different Glossina species were identified i.e. G. tachinoides (52.0%), G. pallidipes (26.0%), G.morsitans submorsitans (15.0%) and G. fuscipes fuscipes (7.0 %). Significant differences in catches/trap/day between districts were observed for each species. No association could be found between the tsetse fly counts and trypanosomosis prevalence. CONCLUSIONS: Trypanosomosis remains a constraint to livestock production in south-western Ethiopia. Four Glossina and three Trypanosoma species were observed. Altitude had a significant impact on AT and PoT. PoT is not associated with AT, which could be explained by the importance of mechanical transmission. This needs to be investigated further as it might jeopardize control strategies that target the tsetse fly population. PMID- 26286486 TI - Do personalised e-mail invitations increase the response rates of breast cancer survivors invited to participate in a web-based behaviour change intervention? A quasi-randomised 2-arm controlled trial. AB - BACKGROUND: Previous research has shown that the personalisation of study invitations improves response rates in survey-based research. To examine if this finding extends to experimental studies, we examined the impact of personalised study invitation e-mails on the response rates of potentially eligible breast cancer survivors for participation in a 6 month randomised controlled trial testing the efficacy of a physical activity intervention. METHODS: Potential participants (n = 344) were sent either a personalised email or a generic email. RESULTS: Those sent the personalised email were 1.5 times (95 % CI = 1.18-1.93) more likely to respond than those sent the generic email. CONCLUSION: These findings suggest that personalisation may be a useful and potentially powerful tool that can be utilised when recruiting participants into experimental studies in order to boost response rates. PMID- 26286487 TI - Intraoperative Schnellschnittuntersuchungen parapylorischer Lymphknoten bei der pyloruserhaltenden Pankreaskopfresektion: Gibt es eine klinische Relevanz? AB - HINTERGRUND: Die pyloruserhaltende Pankreaskopfresektion (PPPD) ist als onkologisches Standardverfahren etabliert. Lokal fortgeschrittene Tumoren konnen eine erweiterte Resektion erforderlich machen. Ebenso soll fruheren Arbeiten zufolge bei Tumornachweis in den parapylorischen Lymphknoten (PLK) eine distale Magenresektion im Sinne einer klassischen Whipple-Operation indiziert sein. Entsprechend diesen Empfehlungen haben wir intraoperative Schnellschnittuntersuchungen der PLK in unseren Routineablauf integriert. Im Rahmen dieser Studie haben wir die klinische Relevanz dieses Vorgehens hinterfragt. METHODEN: Bei 105 onkologischen Patienten im Zeitraum von 2006-2012 bestand die Indikation zur PPPD. In allen Fallen erfolgte eine intraoperative Schnellschnittuntersuchung der PLK. Die Patienten wurden bezuglich Primartumor, Anzahl der untersuchten Lymphknoten (LK) (gesamt und parapylorisch) sowie Auswirkungen auf das operative Konzept untersucht. Es handelt sich um eine retrospektive Studie, die auf prospektiv erhobenen Daten unserer Pankreasdatenbank basiert. ERGEBNISSE: Die Primartumoren waren 72 Pankreaskopfkarzinome und 33 extrapankreatische Karzinome (Gallengangskarzinom, Ampullenkarzinom, Duodenalkarzinom). 73 Patienten waren nodalpositiv. Insgesamt wurden 2391 LK untersucht, von denen 325 parapylorisch lokalisiert waren. Die intraoperative Schnellschnittuntersuchung erbrachte lediglich bei 4 Patienten mit Pankreaskopfkarzinom jeweils einen positiven PLK; daraufhin erfolgte eine distale Magenresektion. In keinem der distalen Magenresektate waren Tumorresiduen nachweisbar. Lokale chirurgisch-technische Probleme im Sinne von Durchblutungsstorungen des Magens ergaben sich durch die regionale Lymphadenektomie nicht. PLK waren nur beim Pankreaskarzinom positiv. In der Subgruppe der nodalpositiven Patienten mit Pankreaskopfkarzinom hatten 8% der Patienten einen positiven PLK. SCHLUSSFOLGERUNG: Die regionale parapylorische Lymphadenektomie ist beim Pankreaskarzinom in einigen (5%) Fallen onkologisch sinnvoll. Der Nutzen einer intraoperativen Schnellschnittuntersuchung mit nachfolgender Konsequenz fur eine etwaige distale Magenresektion ist anhand unserer Daten nicht belegbar. PMID- 26286488 TI - Rasch Analysis of the Profiles of Occupational Engagement in people with Severe mental illness (POES) instrument. AB - PURPOSE: The Profiles of Occupational Engagement in people with Severe mental illness (POES) instrument was developed to study time use profiles of occupations and measure the extent they are characterized by engagement. However, the dimensional factors are not known. The aim of the present study was to establish the internal construct validity of the POES using the Rasch measurement model. METHODS: A sample of 192 outpatients in Sweden was administered the POES and data were subjected to Rasch analysis. RESULTS: The POES showed good fit to the Rasch model after accommodation for local dependency. The nine items had high reliability as measured by person separation index, and no threshold disordering was present. Differential item functioning analysis showed no significant differences across groups of age, sex, diagnosis, or country of origin. CONCLUSION: The POES is a unidimensional scale that represents a continuum of occupational engagement. The transformed POES sum score can be used on an interval scale to measure status and changes in occupational engagement in mental health practice and research. PMID- 26286489 TI - Sex offender risk assessment: A reexamination of the coffee can study. AB - There exists a valid concern among forensic psychology scholars that measures intended for sexual offenders have plateaued in their predictive accuracy. The current study examined this concern using the "coffee can" methodology of Kroner, Mills, and Reddon (2005). The Iowa Sex Offender Risk Assessment (ISORA8), Level of Service Inventory - Revised (LSI-R), and Static-99R were used to predict various methods of detected recidivism (general, sexual, and violent recidivism) as compared to three randomly generated measures and a weighted generated measure. Independent correlation and receiver operating characteristic comparisons found that in almost all cases, generated measures outperformed established measures. Analyses indicated that the current conceptualization of risk for sexual offenders has not been thoroughly integrated into established measures. Current measures appear incomplete, but have a clear and empirically noted ability to improve. PMID- 26286490 TI - [COPD management: what is essential?]. PMID- 26286491 TI - [Factitia: artificial disorders from the internal medicine viewpoint]. PMID- 26286493 TI - [What is your diagnosis?]. PMID- 26286495 TI - [Interstitial cystitis/bladder pain syndrome (IC/BPS)]. AB - Interstitial cystitis/bladder pain syndrome (BPS) is still an etiologically poorly understood chronic pain syndrome. BPS is a clinical diagnosis. The current treatment modalities are aimed at symptom relief because no cure is possible. Analgesics may be used at any point in treatment but preferably for short-term relief for flares or bladder pain. AUA has issued clinical practice guidelines with a stepwise approach. The first-line therapy begins with self-care and behavior modification. Physical therapy and oral medications such as amitriptyline, PPS, or antihistamines belong to the second-line therapy. Third line therapy requires cystoscopy and hydrodistension, treatment of Hunner lesions, or intravesical use of e.g. DMSO. Neuromodulation is considered a fourth line therapy in patients who have failed third-line treatments. Fifth-line therapies consist of intravesical injection of BoNT or oral cyclosporin A. Cystectomy is the sixth-line therapy and the treatment of last resort. PMID- 26286494 TI - Performance Measures in the Management of Chronic Obstructive Pulmonary Disease in Primary Care--A Retrospective Analysis. AB - RATIONALE: Adherence to recommendations regarding quality of care for chronic obstructive pulmonary disease (COPD) improves outcome of patients. Performance measures (PM) reflect the quality of care but information about documentation of PM in primary care, is scant. AIM: To investigate the documentation of COPD PM in primary care practices of the Canton Zurich. METHOD: Twelve months retrospective medical chart review with physician of patients diagnosed COPD. PM were assessed by calculating the percentages of documented performance parameters. In addition, PM were compared with a practice running a structured COPD program. RESULTS: Data from 14 practices, total 115 patients, 57% male, mean age 68 (44-93) years, 46% active smokers, median pack-years 56 (range 22-150) were analyzed. Comorbidities were documented in 73%, GOLD grading in 70% (GOLD I 11%, GOLD II 64%, GOLD III 21%, GOLD IV 4%). On average, patients were reported to have 1,4 exacerbations/year. Documentation of PM ranged between 16% (written action plan for exacerbations) and 95% (smoking status). Documentation was identified for smoking cessation advice (74%), influenza vaccination/recommendation (49%), adequate pharmacotherapy (65%), inhalation instruction (57%), pulmonary rehabilitation advice (27%), collaborative care (60%) and proactive follow up (51%). The practice running the COPD program showed significant better documentation for all PM (p<0,01) but for influenza vaccination. CONCLUSION: In Swiss primary care gaps in documentation and tracking of COPD performance exist. Identifying and bridging these gaps is central for health care quality. PMID- 26286496 TI - ["Not to be taken lightly"]. AB - A 78 year old patient with type 2 diabetes mellitus was hospitalized because of weakness and poor nutritional status. For several years, he suffered from an unintended weight loss and chronic, pulpy diarrhea. On examination, we found a severe loss of muscle and fat tissue as well as difficulty swallowing. An adequate nutritional therapy with combined parenteral and enteral nutrition was implemented under regular monitoring of electrolytes and volume status, under which the state of health improved noticeably, while steatorrhea improved under substitution of pancreatic enzymes. PMID- 26286497 TI - [Epidural steroids for lumbosacral radicular pain treatment is no better than an oral gabapentin]. PMID- 26286498 TI - [Beta-lactam monotherapy in hospitalized pneumonia patients is not inferior to a combined therapy]. PMID- 26286500 TI - [CME - Ultrasonography 65. Peripheral lung consolidation]. PMID- 26286503 TI - Evolution and tinkering: what do a protein kinase, a transcriptional regulator and chromosome segregation/cell division proteins have in common? AB - In this study, we focus on functional interactions among multi-domain proteins which share a common evolutionary origin. The examples we develop are four Bacillus subtilis proteins, which all possess an ATP-binding Walker motif: the bacterial tyrosine kinase (BY-kinase) PtkA, the chromosome segregation protein Soj (ParA), the cell division protein MinD and a transcription regulator SalA. These proteins have arisen via duplication of the ancestral ATP-binding domain, which has undergone fusions with other functional domains in the process of divergent evolution. We point out that these four proteins, despite having very different physiological roles, engage in an unusually high number of binary functional interactions. Namely, MinD attracts Soj and PtkA to the cell pole, and in addition, activates the kinase function of PtkA. SalA also activates the kinase function of PtkA, and it gets phosphorylated by PtkA as well. The consequence of this phosphorylation is the activation of SalA as a transcriptional repressor. We hypothesize that these functional interactions remain preserved during divergent evolution and represent a constraint on the process of evolutionary "tinkering", brought about by fusions of different functional domains. PMID- 26286504 TI - Effects of the Hybridization of Opioid and Neurotensin Pharmacophores on Cell Survival in Rat Organotypic Hippocampal Slice Cultures. AB - Several neurotransmitter and neuromodulatory systems can control physiological glutamatergic activity. For example, opioid receptor ligands were shown to partially inhibit N-methyl-D-aspartic acid (NMDA) receptor-dependent glutamatergic excitotoxicity. Also, the endogenous tridecapeptide neurotensin (NT) was found to modulate excessive glutamate release and glutamate receptor activity in neurons. Alternatively to the one target-one drug approach, it has been well documented that hybrid compounds encompassing two pharmacophores in one molecular scaffold can represent more potent drugs. Moreover, such structures with dual activity can potentially enable a reduction of undesirable side effects and/or improved bioavailability. Herein, we describe the neuroprotective potential of an opioid-NT hybrid peptide (PK20), which was recently designed and synthesized within our group. The protective properties of PK20, assessed in an in vitro model of excitotoxic injury in organotypic hippocampal slice cultures subjected to NMDA, were compared to the effects caused by NT. Our results indicate that PK20 is a potent anti-neurodegenerative agent. Moreover, co administered with NMDA, PK20 (25-100 ng/ml) dose-dependently reduced hippocampal cell death, determined by a decrease in the propidium iodide signal. We also report for the first time the significant NT-induced neuroprotective effect, as its application (50-100 ng/ml) to hippocampal slice cultures protected CA1 damage against neurotoxicity caused by NMDA. PMID- 26286505 TI - Effect of hospice care on quality indicators of end-of-life care among patients with liver cancer: a national longitudinal population-based study in Taiwan 2000 2011. AB - BACKGROUND: Quality of near end-of-life (EOL) care is typically evaluated using six accepted quality indicators (QIs). Research has yet to evaluate the quality of EOL care for liver cancer patients in Taiwan. We evaluated the effect of hospice care on the quality of EOL care for patients with advanced liver cancer. METHODS: Using claims data obtained from the Taiwan National Health Insurance Research Database, we analyzed the QIs of EOL care for patients who died between 2000 and 2011. Logistic regression was performed to identify predictors for QIs of EOL care. RESULTS: A total of 3092 adult patients died of liver cancer during the study period. The patients were divided into those who received hospice care for a period longer than 1 month (long-H group), shorter than 1 month (short-H group), and not at all (non-H group). There was no significant difference in survival probability among the three groups (p = 0.212). Compared with the non-H group, the long- and short-H groups exhibited a significantly lower risk of being admitted to an intensive care unit (ICU) (odds ratios [ORs] = 0.25 and 0.26, respectively, p < 0.001) and requiring cardiopulmonary resuscitation (CPR) during the final month of life (ORs = 0.21 and 0.09, respectively, p < 0.001). Compared with the non-H group, the short-H group had a higher risk of more than one emergency room (ER) visit, and more than one hospital admission (OR = 1.97, p = 0.003; and OR = 1.56, p = 0.001, respectively), but the long-H group did not differed significantly from the non-H group on these measures. CONCLUSIONS: Patients with liver cancer who received hospice care were less likely to be admitted to ICUs or require CPR compared with those who received no hospice care. A longer duration of hospice care was associated with reduced risks of more than one ER visit and more than one hospital admission. We conclude that EOL cancer care in Taiwan might be improved by implementing policies encouraging early hospice referral programs. PMID- 26286506 TI - Protocol for a systematic review: understanding the motivations and barriers to uptake and use of female-initiated, primary biomedical HIV prevention technologies in sub-Saharan Africa. AB - BACKGROUND: Women in sub-Saharan Africa are disproportionately affected by high rates of HIV, yet relatively few products exist for female-initiated HIV prevention. New antiretroviral (ARV)-based prevention options could present opportunities for women to expand their HIV prevention choices; however, acceptability and adherence play a key role in the effectiveness of these products and implementation is still in early stages. To better understand which HIV prevention options might best serve women in sub-Saharan Africa, how and why, this review will explore qualitative evidence from clinical trials and implementation studies alike using a meta-ethnographic approach to synthesise data and interpret results. METHODS/DESIGN: This systematic review will use a meta-ethnographic approach to analyse qualitative data extracted from multiple studies featuring actual use of female-initiated technologies for HIV prevention. The search strategy will be applied in seven databases and papers will be selected using strict inclusion and exclusion criteria. The review will closely follow the guidance set forth by preferred reporting items for systematic reviews and meta-analyses (PRISMA) and Centre for Reviews Dissemination (CRD) where the guidance applies to qualitative data. Two reviewers will review all papers during the paper selection phase, with consultation from a third reviewer to confirm consensus. All papers included in the review will be read and analysed by two reviewers. The final analysis will be conducted by three primary reviewers with additional input from all other authors. DISCUSSION: With new HIV prevention technologies currently in early implementation phases and still more on the horizon, there is much to learn about how best these products may be delivered. A review such as this could help to inform the real-world implementation of the next wave of new HIV prevention technologies such as ARV-based oral pre-exposure prophylaxis (PrEP). PMID- 26286507 TI - Advanced Oxidation Protein Products as a Novel Marker of Oxidative Stress in Postmenopausal Osteoporosis. AB - BACKGROUND: Advanced oxidation protein products (AOPPs) are acknowledged as a novel marker of oxidation-mediated protein damage. This study aimed to investigate the plasma levels of AOPPs in postmenopausal osteoporotic women, and to determine the relationship between AOPPs accumulation and lumbar bone mineral destiny (BMD) or bone turnover markers. MATERIAL AND METHODS: Lumbar BMD was measured by dual-energy X-ray absorptiometry. Plasma AOPPs levels as a marker of protein oxidation damage and malondialdehyde (MDA) levels as a marker of lipid peroxidation were measured by spectrophotometry. The concentrations of 2 specific markers of bone turnover, bone-specific alkaline phosphatase (BALP) and tartrate resistant acid phosphatase5b, (TRACP 5b) were quantified using ELISA kits. RESULTS: We recruited 60 postmenopausal women meeting osteoporosis (OP) diagnostic criteria of World Health Organization (WHO) and 60 postmenopausal women without OP. Plasma levels of AOPPs (P<0.001), BALP (P<0.001) and TRACP 5b (P<0.001) were statistically significantly increased in the postmenopausal osteoporotic women compared with controls, but there was no statistically significant difference in MDA (P=0.124) between the 2 groups. Plasma AOPPs levels were negatively correlated with lumbar BMD and positively correlated with bone turnover markers both in postmenopausal osteoporotic women and in all subjects. However, plasma MDA levels were not correlated with lumbar BMD or bone turnover markers. CONCLUSIONS: In postmenopausal osteoporotic women elevated AOPPs is associated with reduced BMD and increased bone turnover markers. Because AOPPs is stable and easy to detect it may be used as a simple plasma marker to predict the severity of postmenopausal OP. PMID- 26286508 TI - Herboxidiene biosynthesis, production, and structural modifications: prospect for hybrids with related polyketide. AB - Herboxidiene is a polyketide with a diverse range of activities, including herbicidal, anti-cholesterol, and pre-mRNA splicing inhibitory effects. Thus, production of the compound on the industrial scale is in high demand, and various rational metabolic engineering approaches have been employed to enhance the yield. Directing the precursors and cofactors pool toward the production of polyketide compounds provides a rationale for developing a good host for polyketide production. Due to multiple promising biological activities, the production of a number of herboxidiene derivatives has been attempted in recent years in a search for the key to improve its potency and to introduce new activities. Structural diversification through combinatorial biosynthesis was attempted, utilizing the heterologous expression of substrate-flexible glucosyltransferase (GT) and cytochrome P450 in Streptomyces chromofuscus to generate structurally and functionally diverse derivatives of herboxidiene. The successful attempt confirmed that the strain was amenable to heterologous expression of foreign polyketide synthase (PKS) or post-PKS modification genes, providing the foundation for generating novel or hybrid polyketides. PMID- 26286509 TI - Efficiency of hepatitis A virus removal in six sewage treatment plants from central Tunisia. AB - The efficiency of six Tunisian sewage treatment plants (STP) for the removal of hepatitis A virus (HAV) from wastewater was analysed in order to evaluate the potential risk for human health linked to reuse or discharge of treated wastewater into the environment. The STP utilize different biological wastewater treatments including primary treatment, which involves the physical removal of organic and inorganic solids, and secondary treatment that involves different processes, such as activated sludge or lagoon. Quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) and conventional RT-PCR were used for the analysis of the 325 wastewater samples (163 raw and 162 treated) obtained. Results revealed highest contamination in west-central of Tunisia in raw wastewater with 62.96 % of samples positive for HAV and predominance during winter and autumn, whereas east-central region showed 50.62 % of positive samples with high prevalence from winter through summer. The quantitative analysis revealed a range between 4.29 * 10(1) and 1.24 * 10(5) RNA copies/mL in treated wastewater, showing clearly the inefficiency for total removal of HAV regardless of the treatment method used. The vast majority of HAV sequences belonged to the sub-genotype IA, except one that was assigned to sub-genotype IB. PMID- 26286510 TI - Effects of constant or dynamic low anode potentials on microbial community development in bioelectrochemical systems. AB - In bioelectrochemical systems, exoelectrogenic bacteria respire with anode electrodes as their extracellular electron acceptor; therefore, lower anode potentials can reduce the energy gain to each microbe and select against ones that are not able to respire at a lower potential range. Often fully developed anode communities are compared across bioelectrochemical systems with set anode potentials or fixed external resistances as different operational conditions. However, the comparative effect of the resulting constantly low versus dynamically low anode potentials on the development of anode microbial communities as well as the final cathode microbial communities has not been directly demonstrated. In this study, we used a low fixed anode potential of -250 mV and a higher-current control potential of -119 mV vs. Standard Hydrogen Electrode to approximately correspond with the negative peak anode potential values obtained from microbial fuel cells operated with fixed external resistances of 1 kOmega and 47 Omega, respectively. Pyrosequencing data from a 2 month time series show that a lower set anode potential resulted in a more diverse community than the higher- and variable-potential systems, likely due to the hindered enrichment of a Geobacter-dominated community with limited energy gain at this set potential. In this case, it appears that the selective pressure caused by the low set potential was counteracted by the low energy gain over a 2 month time scale. The air cathode microbial community with constant low anode potentials showed delayed enrichment of denitrifiers or perchlorate-reducing bacteria compared to the fixed external resistance condition. PMID- 26286511 TI - Substrate sources regulate spatial variation of metabolically active methanogens from two contrasting freshwater wetlands. AB - There is ample evidence that methane (CH4) emissions from natural wetlands exhibit large spatial variations at a field scale. However, little is known about the metabolically active methanogens mediating these differences. We explored the spatial patterns in active methanogens of summer inundated Calamagrostis angustifolia marsh with low CH4 emissions and permanently inundated Carex lasiocarpa marsh with high CH4 emissions in Sanjiang Plain, China. In C. angustifolia marsh, the addition of (13)C-acetate significantly increased the CH4 production rate, and Methanosarcinaceae methanogens were found to participate in the consumption of acetate. In C. lasiocarpa marsh, there was no apparent increase in the CH4 production rate and no methanogen species were labeled with (13)C. When (13)CO2-H2 was added, however, CH4 production was found to be due to Fen Cluster (Methanomicrobiales) in C. angustifolia marsh and Methanobacterium Cluster B (Methanobacteriaceae) together with Fen Cluster in C. lasiocarpa marsh. These results suggested that CH4 was produced primarily by hydrogenotrophic methanogens using substrates mainly derived from plant litter in C. lasiocarpa marsh and by both hydrogenotrophic and acetoclastic methanogens using substrates mainly derived from root exudate in C. angustifolia marsh. The significantly lower CH4 emissions measured in situ in C. angustifolia marsh was primarily due to a deficiency of substrates compared to C. lasiocarpa marsh. Therefore, we speculate that the substrate source regulates both the type of active methanogens and the CH4 production pathway and consequently contributes to the spatial variations in CH4 productions observed in these freshwater marshes. PMID- 26286512 TI - Effect of inoculum and sulfide type on simultaneous hydrogen sulfide removal from biogas and nitrogen removal from swine slurry and microbial mechanism. AB - Four reactors were initiated to study the effect of inoculum and sulfide type on the simultaneous hydrogen sulfide removal from biogas and nitrogen removal from swine slurry (Ssu-Nir) process. Anaerobic sludge, aerobic sludge, and water were used as inocula, and Na2S and biogas were used as a sulfide substrate, respectively. Additionally, 454 pyrosequencing of the 16S rRNA gene was used to explore the bacterial diversity. The results showed that sulfur-oxidizing bacteria (Thiobacillus, 42.2-84.4 %) were dominant in Ssu-Nir process and led to the excellent performance. Aerobic sludge was more suitable for inoculation of the Ssu-Nir process because it is better for rapidly enriching dominant sulfur oxidizing bacteria (Thiobacillus, 54.4 %), denitrifying sulfur-oxidizing bacteria (40.0 %) and denitrifiers (23.9 %). Lower S(2-) removal efficiency (72.6 %) and NO3 (-) removal efficiency (<90 %) of the Ssu-Nir process were obtained using biogas as a sulfide substrate than when Na2S was used. For the Ssu-Nir process with biogas as the sulfide substrate, limiting H2S absorption caused a high relative abundance of sulfur-oxidizing bacteria, Thiobacillus (84.8 %) and Thiobacillus sayanicus (39.6 %), which in turn led to low relative abundance of denitrifiers (1.6 %) and denitrifying sulfur-oxidizing bacteria (24.4 %), low NO3 (-) removal efficiency, and eventually poor performance. PMID- 26286513 TI - Evaluation of soil bioremediation techniques in an aged diesel spill at the Antarctic Peninsula. AB - Many areas on the Antarctic continent already suffer from the direct and indirect influences of human activities. The main cause of contamination is petroleum hydrocarbons because this compound is used as a source of energy at the many research stations around the continent. Thus, the current study aims to evaluate treatments for bioremediation (biostimulation, bioaugmentation, and bioaugmentation + biostimulation) using soils from around the Brazilian Antarctic Station "Comandante Ferraz" (EACF), King George Island, Antarctic Peninsula. The experiment lasted for 45 days, and at the end of this period, chemical and molecular analyses were performed. Those analyses included the quantification of carbon and nitrogen, denaturing gradient gel electrophoresis (DGGE) analysis (with gradient denaturation), real-time PCR, and quantification of total hydrocarbons and polyaromatics. Molecular tests evaluated changes in the profile and quantity of the rrs genes of archaea and bacteria and also the alkB gene. The influence of the treatments tested was directly related to the type of soil used. The work confirmed that despite the extreme conditions found in Antarctic soils, the bacterial strains degraded hydrocarbons and bioremediation treatments directly influenced the microbial communities present in these soils even in short periods. Although the majority of the previous studies demonstrate that the addition of fertilizer seems to be most effective at promoting bioremediation, our results show that for some conditions, autochthonous bioaugmentation (ABA) treatment is indicated. This work highlights the importance of understanding the processes of recovery of contaminated environments in polar regions because time is crucial to the soil recovery and to choosing the appropriate treatment. PMID- 26286514 TI - Mechanisms of fatty acid synthesis in marine fungus-like protists. AB - Thraustochytrids are unicellular fungus-like protists and are well known for their ability to produce interesting nutraceutical compounds. Significant efforts have been made to improve their efficient production of important fatty acids (FAs), mostly by optimizing fermentation conditions and selecting highly productive thraustochytrid strains. Furthermore, noticeable improvements have been made in understanding the mechanism of FA biosynthesis, allowing for a better understanding of how thraustochytrids assemble these unique metabolites and how their biosynthesis is coupled with other related pathways. This review summarizes recent achievements on two major FA biosynthesis pathways, the standard pathway and the polyketide synthase pathway, and detail features of individual enzymes involved in FA biosynthesis, biotechnological advances in pathway engineering and enzyme characterization, and the discovery of other pathways that affect the efficiency of FA accumulation. Perspectives of biotechnological potential application of thraustochytrids are also discussed. PMID- 26286515 TI - Microbial community in a hydrogenotrophic denitrification reactor based on pyrosequencing. AB - Effects of some key factors on hydrogenotrophic denitrification were investigated in lab-scale bioreactors. Results indicated that optimum biomass loading, pH value, temperature, nitrate loading, and C/N ratio in this study were optical density at 600 nm (OD600) of 0.173, 6.0~7.0, 35 degrees C, 105 mg L(-1), and 30, respectively. To obtain a better understanding of microbial community in the bioreactors, the 454-pyrosequencing technology was used to characterize the 16S ribosomal RNA (16S rRNA) gene of bacteria in selected samples Y1 and Y2, in which a total of 62,559 effective sequences (36,445 in Y1 and 26,114 in Y2) were obtained. The taxonomic complexities in two samples were compared at phylum/class/genus levels. In total, 41 bacterial phyla, 43 bacterial classes, and 312 genera were detected, where phylum Firmicutes, class Clostridia were most abundant. Genus Proteiniclasticum was predominant among the top 100 genera. This work aims to add some novel insights into hydrogenotrophic denitrification process and its microbial community structures in bioreactors. PMID- 26286517 TI - Erratum: Robust disruptions in electroencephalogram cortical oscillations and large-scale functional networks in autism. PMID- 26286516 TI - Divergent cerebrospinal fluid cytokine network induced by non-viral and different viral infections on the central nervous system. AB - BACKGROUND: Meningoencephalitis is one of the most common disorders of the central nervous system (CNS) worldwide. Viral meningoencephalitis differs from bacterial meningitis in several aspects. In some developing countries, bacterial meningitis has appropriate clinical management and chemotherapy is available. Virus-associated and virus not detected meningoencephalitis are treatable, however, they may cause death in a few cases. The knowledge of how mediators of inflammation can induce disease would contribute for the design of affordable therapeutic strategies, as well as to the diagnosis of virus not detected and viral meningoencephalitis. Cytokine-induced inflammation to CNS requires several factors that are not fully understood yet. METHODS: Considering this, several cytokines were measured in the cerebrospinal fluid (CSF) of patients with undiagnosed and viral meningoencephalitis, and these were correlated with cellularity in the CSF. RESULTS: The results demonstrate that an altered biochemical profile alongside increased cellularity in the cerebrospinal fluid is a feature of patients with meningoencephalitis that are not associated with the detection of virus in the CNS (P < 0.05). Moreover, HIV-positive patients (n = 10) that evolve with meningoencephalitis display a distinct biochemical/cytological profile (P < 0.05) in the cerebrospinal fluid. Meningoencephalitis brings about a prominent intrathecal cytokine storm regardless of the detection of virus as presumable etiological agent. In the case of Enterovirus infection (n = 13), meningoencephalitis elicits robust intrathecal pro-inflammatory cytokine pattern and elevated cellularity when compared to herpesvirus (n = 15) and Arbovirus (n = 5) viral infections (P < 0.05). CONCLUSION: Differences in the cytokine profile of the CSF may be unique if distinct, viral or presumably non-viral pathways initially trigger the inflammatory response in the CNS. PMID- 26286518 TI - Close concordance between pulmonary angiography and pathology in a canine model with chronic pulmonary thromboembolism and pathological mechanisms after lung ischemia reperfusion injury. AB - To investigate the pulmonary angiography and pathology in a canine model with chronic pulmonary thromboembolism (PTE). The cylindrical blood clots were selectively introduced into the left (n = 10) or right (n = 20) lower pulmonary arteries of dogs. Pulmonary arteriography (PA) was performed before or after embolization. The values after embolization and baseline of mean pulmonary arterial pressure, pulmonary vascular resistance, cardiac output had changed. After 1 or 2 weeks' embolization, local PA demonstrated the abrupt cut-off perfusion defects or webs, bands, and abrupt vascular narrowing. 2 weeks after embolization, the pathology showed that the fibrin networks of the thrombi had multiple recanalization channels, and pulmonary artery had the concentric, lamellar (onion-like) intimal hyperplasia, multilayered, irregular arrangements of endothelial cells, and the infiltration of inflammatory cells. After embolectomy-mediated reperfusion, 2 weeks' subgroup showed destroyed and incomplete alveolar structures, and a large number of exudative cells, primarily neutrophils, and exudate. There close concordance between pulmonary angiography and pathology in a canine model with chronic PTE. The LIRI mechanisms after embolectomy-mediated reperfusion involve the destroyed, incomplete alveolar structures, and infiltration of inflammatory cells, primarily neutrophils. PMID- 26286519 TI - "The keeping is the problem": A qualitative study of IRB-member perspectives in Botswana on the collection, use, and storage of human biological samples for research. AB - BACKGROUND: Concurrent with efforts to establish national and regional biorepositories in Africa is widespread endorsement of ethics committees as stewards of the interests of individual donors and their communities. To date, ethics training programs for IRB members in Botswana have focused on ethical principles and international guidelines rather than on the ethical dimensions of specific medical technologies and research methodologies. Little is known about the knowledge and concerns of current and prospective IRB members in Botswana with respect to export, reuse, storage, and benefit-sharing of biospecimens. METHODS: This qualitative study examined perspectives of IRB members in Botswana about the collection and use of biospecimens in research. Forty-one IRB members representing five committees in Botswana participated in discussions groups in March 2013. Transcriptions of audiotapes and field notes were analyzed to identify issues of concern that might be alleviated through education and capacity-building, and areas that required ongoing discussion or additional regulatory guidance. RESULTS: Areas of concern included lack of understanding among patients and providers about the use of biospecimens in clinical care and research; reuse of biospecimens, particularly issues of consent, ownership and decision-making; export of specimens and loss of control over reuse and potential benefits; and felt need for regulatory guidance and IRB-member training. Local belief systems about bodily integrity and strong national identity in the construct of benefits may be at odds with initiatives that involve foreign biorepositories or consider such collections to be global public goods. CONCLUSION: Education is needed to strengthen IRB-member capacity to review and monitor protocols calling for the collection and use of biospecimens, guided by clear national policy on priority-setting, partnerships, review, and oversight. Engagement with local stakeholders is needed to harmonize fundamentally different ways of understanding the human body and community identity with the aims of contemporary biomedicine. PMID- 26286520 TI - A body shape index and body roundness index: two new body indices to identify diabetes mellitus among rural populations in northeast China. AB - BACKGROUND: The Body Mass Index (BMI) has long been used as an anthropometric measurement. Waist circumference (WC) and waist-to-height ratio (WHtR) have been proposed as alternatives to BMI. Recently, two new anthropometric indices, the A Body Shape Index (ABSI) and Body Roundness Index (BRI) have been developed as possible improved alternatives to BMI and WC. The main research aim is to assess the capacity of the ABSI and BRI to identify subjects with diabetes mellitus (DM) and the secondary aim is to determine whether ABSI and/or BRI is superior to the traditional body indices (BMI, WC, and WHtR). METHODS AND RESULTS: This cross sectional study was conducted in the rural areas of northeast China from January 2012 to August 2013, and the final analysis included data obtained form 5253 men and 6092 women. 1182 participants (10.4 %) suffered from DM. Spearman rank test showed that BRI and WHtR showed the highest Spearman correlation coefficient for DM whereas ABSI showed the lowest. The prevalence of DM increased across quartiles for ABSI, BMI, BRI, WC and WHtR. A multivariate logistic regression analysis of the presence of DM for the highest quartile vs. the lowest quartile of each anthropometric measure, showed that the WHtR was the best predictor of DM (OR: 2.40, 95 % CI: 1.42-3.39 in men; OR: 2.67, 95 % CI: 1.60-3.74 in women, both P < 0.001), and the ABSI was the poorest predictor of DM (OR: 1.51, 95 % CI: 1.05 1.97 in men; OR: 1.55, 95 % CI: 1.07-2.04 in women, both P < 0.05). ABSI showed the lowest AUCs (AUC: 0.61, 95 % CI: 0.58-0.63 for men; AUC: 0.61, 95 % CI: 0.59 0.63 for women) for DM in both sexes, while BRI (AUC: 0.66, 95 % CI: 0.63-0.68 for men; AUC: 0.67, 95 % CI: 0.65-0.69 for women) had high AUCs for DM that equaled those of WHtR. CONCLUSIONS: Our results showed neither ABSI nor BRI were superior to BMI, WC, or WHtR for predicting the presence of DM. ABSI showed the weakest predictive ability, while BRI showed potential for use as an alternative obesity measure in assessment of DM. PMID- 26286521 TI - Melatonin, quercetin and resveratrol attenuates oxidative hepatocellular injury in streptozotocin-induced diabetic rats. AB - In this study, effects of melatonin, quercetin and resveratrol on hepatocellular injury in streptozotocin (STZ)-induced experimental diabetes were aimed to be investigated by histological and biochemical methods. Thirty-five male Wistar albino rats were divided into five groups, namely, control, diabetes (STZ 45 mg/kg/single dose/intraperitoneally (ip)), diabetes + melatonin (10 mg/kg/30 days/ip), diabetes + quercetin (25 mg/kg/30 days/ip) and diabetes + resveratrol (10 mg/kg/30 days/ip). Initial and final blood glucose levels and body weights (BWs) were measured. At the end of the experimentation, following routine tissue processing procedure, sections were stained with haematoxylin-eosin (H-E), periodic acid Schiff and Masson's trichrome. Tissue malondialdehyde (MDA) and glutathione (GSH) levels and superoxide dismutase (SOD) and catalase (CAT) activities were examined. The diabetic rats had significantly higher blood glucose levels than those of control rats (p = 0.0001). Mean BWs of diabetic rats were significantly decreased when compared with the control rats (p = 0.0013). Histopathological alterations including cellular glycogen depletion, congestion, sinusoidal dilatation, inflammation and fibrosis were detected in diabetes group. On the other hand, histopathological changes markedly reduced in all of the treatment groups (p = 0.001). Mean tissue MDA level was increased but mean tissue CAT and SOD activities and GSH levels were decreased in the diabetes group. Melatonin, quercetin and resveratrol administered diabetic rats showed an increase in CAT activities and GSH levels and a decrease in MDA levels (p < 0.05, for all). Melatonin, quercetin and resveratrol administrations markedly reduced hepatocellular injury in STZ-induced experimental diabetes. PMID- 26286522 TI - Glucose uptake through translocation and activation of GLUT4 in PI3K/Akt signaling pathway by asiatic acid in diabetic rats. AB - In this study, we examined the in vivo effect and the mechanism of asiatic acid (AA) on glucose uptake in an insulin target skeletal muscle. Diabetic rats showed significantly increased levels of plasma glucose, thiobarbituric acid reactive substances, and lipid hydroperoxides, decreased levels of insulin and antioxidants, and impairment in insulin-signaling proteins such as insulin receptor (IR), insulin receptor substrate (IRS)-1/2, phosphoinositide 3-kinase (PI3K), Akt, and glucose transporter 4 (GLUT4) proteins. Oral treatment with AA (20 mg/kg body weight) showed near-normalized levels of plasma glucose, lipid peroxidation products, and antioxidants and improved insulin, IR, IRS-1/2, PI3K, Akt, and GLUT4 proteins. These findings suggest that AA improves glucose response by increasing GLUT4 in skeletal muscle through Akt and antioxidant defense in plasma and it also improves glucose homeostasis. PMID- 26286523 TI - Enicostemma littorale prevents tumor formation in 7,12-dimethylbenz(a)anthracene induced hamster buccal pouch carcinogenesis. AB - Oral cancer is one of the most common malignancies worldwide, and India has recorded the highest annual incidence of oral cancer in comparison with other countries. Altered lipid peroxidation and antioxidant status along with defect in detoxification cascade have been implicated in the pathogenesis of several cancers including oral cancer. The aim of this study was to investigate the chemopreventive potential of ethanolic extract of Enicostemma littorale leaves (ElELet) in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Oral tumor was developed in the buccal pouches of male golden Syrian hamsters by painting with 0.5% DMBA three times a week for 14 weeks. We observed 100% tumor formation with increase in tumor volume and tumor burden in the hamsters treated with DMBA alone. Imbalance in phase I (cytochrome P450 and cytochrome b5) and phase II (glutathione reductase, glutathione-S-transferase, glutathione, and Deoxythymidine-diaphorase (DT)-diaphorase) detoxification agents and lipid peroxidation by-products (thiobarbituric acid reactive substances) and antioxidant (superoxide dismutase, catalase, glutathione peroxidase, and vitamins E and C) status was noticed in hamsters treated with DMBA alone. Oral administration of ElELet at a dose of 250 mg/kg body weight to hamsters treated with DMBA significantly prevented both precancerous and cancerous lesions in the oral cavity. ElELet modulated the status of phase I and II detoxification agents and antioxidants in favor of the suppression of oral carcinogenesis. This study thus suggests that E. littorale might have inhibited the oral carcinogenesis in DMBA-treated hamsters through its antioxidant potential. The present findings are also substantiated by histological studies during DMBA-induced oral carcinogenesis. PMID- 26286524 TI - Beyond the 5-HT3 receptors: A role for alpha7nACh receptors in neuroprotective aspects of tropisetron. AB - Accumulation of reactive oxygen species, such as hydrogen peroxide (H2O2), generated by inflammatory cells or other pathological conditions, leads to oxidative stress, which may contribute to the neuronal degeneration observed in a wide variety of neurodegenerative disorders such as Alzheimer's disease. Recent investigations have described effective properties of tropisetron, such as antiphlogistic action or protection against beta-amyloid induced neuroinflammation in rats. Our data revealed that H2O2-induced cell death in rat pheochromocytoma cell line (PC12) can be inhibited by tropisetron, as defined by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide assay, caspase 3 and caspase 12 levels. We further showed that tropisetron exerts its protective effects by upregulation of heme oxygenase-1, glutathione, catalase activity, and nuclear factor-erythroid 2 p45-related factor 2 level. Moreover, tropisetron was recently found to be a partial agonist of alpha7 nicotinic acetylcholine receptor (alpha7nAChR). The activation of alpha7nAChR could inhibit inflammatory and apoptotic signaling pathways in the oxidative stress conditions. In this study, selective alpha7nAChR antagonists (methyllycaconitine) reversed the effects of tropisetron on caspase 3 level. Our findings indicated that tropisetron can protect PC12 cells against H2O2-induced neurotoxicity through alpha7nAChR in vitro. PMID- 26286525 TI - Identification of hepatitis B and C screening and patient management guidelines and availability of training for chronic viral hepatitis among health professionals in six European countries: results of a semi-quantitative survey. AB - BACKGROUND: As part of the EU funded project "HEPscreen", the aim of this study is to identify hepatitis B and C screening and patient management guidelines, to assess the awareness of these among health professionals (HPs) and to explore the availability of hepatitis B/C training programmes for HPs in Germany, Italy, the Netherlands, the UK, Spain and Hungary. METHODS: A comprehensive literature search through the main scientific databases was performed to retrieve guidelines, following which an online survey was developed and sent to HPs in six areas of health care, including public health, to verify whether HPs are aware of these guidelines, to retrieve additional guidelines and to find out whether specific professional training is available. RESULTS: Twelve national guidelines were identified through the literature search. Of the 268 respondents, 80 % were aware of hepatitis B guidelines and 73 % were aware of hepatitis C guidelines in their country. The national guidelines identified through the literature search were mentioned by 1/3 of HPs in the UK and Germany, 13 % of HPs in the Netherlands, 14 % in Italy and 4 % in Spain. An additional 41 hepatitis B/C related guidance documents were retrieved through the online survey: 15 in the UK, seven in Hungary, six in Italy, five in the Netherlands, four in Germany and four in Spain. Availability of training programmes to improve skills and knowledge in viral hepatitis was most often reported in the Netherlands, with 82 % indicating availability and just 10 % indicating no availability, and least commonly in Italy, with 42 % indicating yes but 40 % indicating no. Availability was also reported by the majority in the UK, Hungary and Spain, while in Germany the majority selected unsure. CONCLUSIONS: Results suggest that the scientific databases are not the most important information source of best clinical practice for many HPs. Implementation of best practices requires that guidelines are specifically designed and actively promoted among those who are to follow them. Training can disseminate these best practice recommendations and raise awareness of guidelines. It is therefore encouraging that diverse training about hepatitis B/C is available to the different professional groups. PMID- 26286527 TI - Appropriate timing and intensity of PC6 stimulation for the prevention of postoperative nausea and vomiting. PMID- 26286526 TI - Cost of care and social consequences of very low birth weight infants without premature- related morbidities in Italy. AB - Aim of this study was to estimate the cost that is borne by the Italian National Health Service, families, and social security due to very low birth weight infants (VLBWIs) without prematurity-related morbidities up to the age of 18 months. We followed up on 150 VLBWIs and 145 comparable full-term infants (FTIs) who were born in one of 25 different neonatal intensive care units upon discharge from the hospital and at six and 18 months of age. The average length of the primary hospitalisation of the VLBWIs was 59.7 days (SD 21.6 days), with a total cost of ?20,502 (SD ?8409), compared with three days (SD 0.4 days) with a total cost of ?907 (SD ?304) for the FTIs. The total societal cost of the VLBWIs for the first 18 months of life was ?58,098 (SD ?21,625), while the corresponding figure for FTIs was ?24,209 (SD ?15,557). Among VLBWIs, both low birth weight and gestational age were correlated with the length of hospitalisation after birth (r(2) = 0.61 and r(2) = 0.57, respectively; p values < 0.0005). Our findings highlight that the existing DRGs and tariffs inadequately reflect the actual costs for Italian National Health Service. PMID- 26286529 TI - Oxidant-Controlled Catalytic Transformations of Phenols with Unexpected Cleavage of Aromatic Rings. AB - Oxidative transformations of phenols have attracted significant attention of chemists due to their importance in biological process and organic synthesis. In contrast to the relatively well-developed oxygenation and coupling reactions of phenols, the highly efficient and selective oxidative ring cleavage of phenols is under-represented. This work describes a novel CuCl-catalyzed tandem homocoupling/skeletal rearrangement of phenols that realizes the cleavage of the phenol ring by using air or Ag2CO3 as the oxidant. Interestingly, simply changing the oxidant to K2S2O8 results in the oxidative coupling/cyclization of phenols to give dibenzofurans. These results set an important precedent of oxidant controlled catalytic transformations of phenols. PMID- 26286528 TI - Identification of inhibitors that target dual-specificity phosphatase 5 provide new insights into the binding requirements for the two phosphate pockets. AB - BACKGROUND: Dual-specificity phosphatase-5 (DUSP5) plays a central role in vascular development and disease. We present a p-nitrophenol phosphate (pNPP) based enzymatic assay to screen for inhibitors of the phosphatase domain of DUSP5. METHODS: pNPP is a mimic of the phosphorylated tyrosine on the ERK2 substrate (pERK2) and binds the DUSP5 phosphatase domain with a Km of 7.6 +/- 0.4 mM. Docking followed by inhibitor verification using the pNPP assay identified a series of polysulfonated aromatic inhibitors that occupy the DUSP5 active site in the region that is likely occupied by the dual-phosphorylated ERK2 substrate tripeptide (pThr-Glu-pTyr). Secondary assays were performed with full length DUSP5 with ERK2 as substrate. RESULTS: The most potent inhibitor has a naphthalene trisulfonate (NTS) core. A search for similar compounds in a drug database identified suramin, a dimerized form of NTS. While suramin appears to be a potent and competitive inhibitor (25 +/- 5 MUM), binding to the DUSP5 phosphatase domain more tightly than the monomeric ligands of which it is comprised, it also aggregates. Further ligand-based screening, based on a pharmacophore derived from the 7 A separation of sulfonates on inhibitors and on sulfates present in the DUSP5 crystal structure, identified a disulfonated and phenolic naphthalene inhibitor (CSD (3) _2320) with IC50 of 33 MUM that is similar to NTS and does not aggregate. CONCLUSIONS: The new DUSP5 inhibitors we identify in this study typically have sulfonates 7 A apart, likely positioning them where the two phosphates of the substrate peptide (pThr-Glu-pTyr) bind, with one inhibitor also positioning a phenolic hydroxyl where the water nucleophile may reside. Polysulfonated aromatic compounds do not commonly appear in drugs and have a tendency to aggregate. One FDA-approved polysulfonated drug, suramin, inhibits DUSP5 and also aggregates. Docking and modeling studies presented herein identify polysulfonated aromatic inhibitors that do not aggregate, and provide insights to guide future design of mimics of the dual-phosphate loops of the ERK substrates for DUSPs. PMID- 26286530 TI - Reclassification of Angiococcus disciformis, Cystobacter minus and Cystobacter violaceus as Archangium disciforme comb. nov., Archangium minus comb. nov. and Archangium violaceum comb. nov., unification of the families Archangiaceae and Cystobacteraceae, and emended descriptions of the families Myxococcaceae and Archangiaceae. AB - The species Archangium gephyra, Angiococcus disciformis, Cystobacter minus and Cystobacter violaceus are currently classified in three different genera of the order Myxococcales. The 16S rRNA gene sequences of the respective type strains show a similarity higher than 98.4 % and form a tight phylogenetic group. A dendrogram calculating the similarity of MALDI-TOF spectra confirmed the close relatedness of the four species that grouped in a monophyletic cluster in the neighbourhood of other species of the genus Cystobacter. The type strains shared similar fatty acid patterns of high complexity with iso-C15 : 0, C16 : 1omega5c and iso-C14 : 0 3-OH as the major components. The vegetative cells of these species are uniformly long needle-shaped rods, and the myxospores are short rods, ovoid or irregularly spherical thus differing from the myxospores of species related to Cystobacter fuscus, the type species of this genus. Some enzymic and hydrolysing reactions of the type strains are described. As a result of the high relatedness and similarity of the four species, it is proposed to place them into one genus, and due to phylogenetic and morphological distinctness, the species should be classified in a genus distinct from the genus Cystobacter as Archangium gephyra (type strain M18T = DSM 2261T = ATCC 25201T = NBRC 100087T), Archangium disciforme comb. nov. (type strain CMU 1T = DSM 52716T = ATCC 33172T), Archangium minus comb. nov. (proposed neotype strain Cb m2 = DSM 14751 = JCM 12627) and Archangium violaceum comb. nov. (type strain Cb vi61T = DSM 14727T = CIP 109131T = JCM 12629T). Since the family ArchangiaceaeJahn 1924 AL has priority over the family CystobacteraceaeMcCurdy 1970 AL, it is proposed to assign the genera Archangium, Anaeromyxobacter, Cystobacter, Hyalangium, Melittangium and Stigmatella to the family Archangiaceae. Emended descriptions of the families Myxococcaceae and Archangiaceae are also provided. PMID- 26286531 TI - Cannabis use in first episode psychosis: Meta-analysis of prevalence, and the time course of initiation and continued use. AB - OBJECTIVES: Cannabis use is prevalent among people with first episode psychosis and the epidemiology of its use in early psychosis is unclear. We performed a meta-analysis of observational studies to determine; (1) the interval between age at initiation of cannabis use and age at onset of first episode psychosis, (2) the prevalence of cannabis use at time of first episode psychosis, and (3) the odds of continuing cannabis following treatment for first episode psychosis. DATA SOURCES: Search of electronic databases MEDLINE, EMBASE, PsycINFO, Web of Science and CINAHL for English-language papers using search terms (psychosis OR schizophrenia) AND (cannabis OR marijuana) IN (title OR keyword OR abstract), current to October 2014. STUDY SELECTION: Studies were included if they reported on prevalence of current cannabis use in first episode psychosis cohorts. A total of 37 samples were included for meta-analysis. DATA EXTRACTION: Rates of cannabis use in each sample were extracted to determine prevalence estimates. The age at initiation of regular cannabis and age at onset of psychosis were used to determine the length of cannabis use preceding psychosis. Prevalence estimates at first episode psychosis and various time points of follow-up following first episode psychosis were analysed to determine odds ratio of continuing cannabis use. Data synthesis was performed using random-effects meta-analyses. RESULTS: The pooled estimate for the interval between initiation of regular cannabis use and age at onset of psychosis was 6.3 years (10 samples, standardised mean difference = 1.56, 95% confidence interval = [1.40, 1.72]). The estimated prevalence of cannabis use at first episode psychosis was 33.7% (35 samples, 95% confidence interval = [31%, 39%]). Odds of continued cannabis use between 6 months and 10 years following first episode psychosis was 0.56 (19 samples, 95% confidence interval = [0.40, 0.79]). PMID- 26286532 TI - Prediction of pain outcomes in a randomized controlled trial of dose-response of spinal manipulation for the care of chronic low back pain. AB - BACKGROUND: No previous studies have created and validated prediction models for outcomes in patients receiving spinal manipulation for care of chronic low back pain (cLBP). We therefore conducted a secondary analysis alongside a dose response, randomized controlled trial of spinal manipulation. METHODS: We investigated dose, pain and disability, sociodemographics, general health, psychosocial measures, and objective exam findings as potential predictors of pain outcomes utilizing 400 participants from a randomized controlled trial. Participants received 18 sessions of treatment over 6-weeks and were followed for a year. Spinal manipulation was performed by a chiropractor at 0, 6, 12, or 18 visits (dose), with a light-massage control at all remaining visits. Pain intensity was evaluated with the modified von Korff pain scale (0-100). Predictor variables evaluated came from several domains: condition-specific pain and disability, sociodemographics, general health status, psychosocial, and objective physical measures. Three-quarters of cases (training-set) were used to develop 4 longitudinal models with forward selection to predict individual "responders" (>=50% improvement from baseline) and future pain intensity using either pretreatment characteristics or post-treatment variables collected shortly after completion of care. The internal validity of the predictor models were then evaluated on the remaining 25% of cases (test-set) using area under the receiver operating curve (AUC), R(2), and root mean squared error (RMSE). RESULTS: The pretreatment responder model performed no better than chance in identifying participants who became responders (AUC = 0.479). Similarly, the pretreatment pain intensity model predicted future pain intensity poorly with low proportion of variance explained (R(2) = .065). The post-treatment predictor models performed better with AUC = 0.665 for the responder model and R(2) = 0.261 for the future pain model. Post-treatment pain alone actually predicted future pain better than the full post-treatment predictor model (R(2) = 0.350). The prediction errors (RMSE) were large (19.4 and 17.5 for the pre- and post treatment predictor models, respectively). CONCLUSIONS: Internal validation of prediction models showed that participant characteristics preceding the start of care were poor predictors of at least 50% improvement and the individual's future pain intensity. Pain collected shortly after completion of 6 weeks of study intervention predicted future pain the best. PMID- 26286533 TI - Long-term outcomes after acute primary angle closure in a White Caucasian population. AB - INTRODUCTION: Very limited data is available on the morbidity and progression to primary angle closure glaucoma (PACG) in White Caucasian individuals following acute primary angle closure (APAC). Our aim is to identify the number of eyes who developed PACG following an APAC attack and to determine the risk factors for PACG development in a White Caucasian population in the United Kingdom (UK). We assessed the rate of blindness and visual impairment in the affected eye as defined by the World Health Organisation. METHODS: Retrospective observational study including 48 consecutive eyes of 46 White Caucasian subjects who presented with APAC to a tertiary referral unit in the United Kingdom. Eyes affected by glaucomatous optic neuropathy at presentation were excluded. We included in our analysis socio-demographic variables, ophthalmic findings, investigations and treatment. RESULTS: The mean final follow up period was 27 months +/- 14 standard deviation (SD). Seven (15 %) eyes developed PACG. Statistical analysis showed that the following factors were linked to a higher risk of progression: length of symptoms before presentation and time taken to break the attack. The intraocular pressure (IOP) was significantly higher in the group who developed PACG at the one- and six-month visit compared to the group which did not develop the disease. At the final visit 3 (6 %) eyes were blind while 5 (10 %) were visually impaired. PACG was responsible for visual impairment in 2 (4 %) eyes but not for any case of blindness. CONCLUSIONS: Delayed presentation, length of time taken to break the attack and poor IOP control can result in PACG development and visual impairment. APAC causes a low long-term visual morbidity in White Caucasians. PMID- 26286534 TI - Investigation of the relationship between the onset of arthritis and uveitis in genetically predisposed SKG mice. AB - INTRODUCTION: Systemic rheumatic conditions are often accompanied by intraocular inflammatory disease (termed uveitis). Despite the frequent manifestation of uveitis with arthritis, very little is understood of the underlying mechanisms that mediate the eye's susceptibility to disease. The genetically susceptible SKG mouse strain develops arthritis that arises from an inherent mutation that disrupts T-cell antigen receptor signal transduction and thymic selection. The ensuing T-cell-mediated disease is further modulated through exposure to microbial triggers. The purpose of this study was to elucidate how a genetically determined shift in the T-cell repertoire toward self-reactive T cells that drive arthritis influences uveitis in SKG mice. METHODS: SKG mice (BALB/c mice that harbor the W163C point mutation in zeta-chain-associated protein kinase 70 [i.e., ZAP-70]) were housed under arthritis-resistant, specific pathogen-free conditions. Arthritis was induced by intraperitoneal injection with fungal glucans (zymosan or curdlan). Arthritis onset and severity were evaluated by clinical scoring, histopathology and infrared imaging within the joints. Periocular traits involving blepharoconjunctivitis were evaluated by clinical scoring and histology. Eyes were evaluated for signs of anterior uveitis using intravital videomicroscopy to document cell-trafficking responses within the iris vasculature and stroma and by histology to detect inflammatory infiltrate and tissue damage within the anterior and posterior eye segments. RESULTS: Exposure to zymosan resulted in the predicted arthritic, sexually dimorphic phenotype in SKG mice. The eyes of SKG mice exhibited episodic intravascular cellular responses to zymosan or curdlan as indicated by significant increases in leukocyte-endothelium interactions akin to ocular vasculitis. However, despite the significant increase in early cell-trafficking responses, cellular infiltration into the iris stroma was not observed and histopathological signs indicative of a sustained uveitis were absent. Instead, eyes of SKG mice developed blepharoconjunctivitis that coincided with arthritis and exhibited sexual dimorphism. CONCLUSIONS: This study underscores the complexity surrounding the pathogenesis of uveitis and its relationship with arthritis. The findings suggest that distinct mechanisms exist by which pathogenic autoimmune T cells target the eyes versus joints, which likely involves the environmental context but nonetheless should be taken into account in the identification and development of effective therapies for each organ. PMID- 26286535 TI - Characteristics of Plant Essential Genes Allow for within- and between-Species Prediction of Lethal Mutant Phenotypes. AB - Essential genes represent critical cellular components whose disruption results in lethality. Characteristics shared among essential genes have been uncovered in fungal and metazoan model systems. However, features associated with plant essential genes are largely unknown and the full set of essential genes remains to be discovered in any plant species. Here, we show that essential genes in Arabidopsis thaliana have distinct features useful for constructing within- and cross-species prediction models. Essential genes in A. thaliana are often single copy or derived from older duplications, highly and broadly expressed, slow evolving, and highly connected within molecular networks compared with genes with nonlethal mutant phenotypes. These gene features allowed the application of machine learning methods that predicted known lethal genes as well as an additional 1970 likely essential genes without documented phenotypes. Prediction models from A. thaliana could also be applied to predict Oryza sativa and Saccharomyces cerevisiae essential genes. Importantly, successful predictions drew upon many features, while any single feature was not sufficient. Our findings show that essential genes can be distinguished from genes with nonlethal phenotypes using features that are similar across kingdoms and indicate the possibility for translational application of our approach to species without extensive functional genomic and phenomic resources. PMID- 26286536 TI - Lost in Translation: Pitfalls in Deciphering Plant Alternative Splicing Transcripts. AB - Transcript annotation in plant databases is incomplete and often inaccurate, leading to misinterpretation. As more and more RNA-seq data are generated, plant scientists need to be aware of potential pitfalls and understand the nature and impact of specific alternative splicing transcripts on protein production. A primary area of concern and the topic of this article is the (mis)annotation of open reading frames and premature termination codons. The basic message is that to adequately address expression and functions of transcript isoforms, it is necessary to be able to predict their fate in terms of whether protein isoforms are generated or specific transcripts are unproductive or degraded. PMID- 26286537 TI - Febrile seizures. PMID- 26286539 TI - Piriformis muscle syndrome: a recurrent case after surgical release. AB - We report a recurrent Piriformisc muscle syndrome after surgical release. After the primary neurolysis, a second operation was performed to release adhesions. This case shows a different type of sciatic nerve entrapment by an abnormal thin muscle slip. Results of the revision surgery guide us to the point that revision surgery for Piriformis muscle syndrome should be meticulously selected, and after considering medical and interventional therapies. PMID- 26286538 TI - Design of, and enrollment in, the palliative care communication research initiative: a direct-observation cohort study. AB - BACKGROUND: Understanding the characteristics of communication that foster patient-centered outcomes amid serious illness are essential for the science of palliative care. However, epidemiological cohort studies that directly observe clinical conversations can be challenging to conduct in the natural setting. We describe the successful enrollment, observation and data collection methods of the ongoing Palliative Care Communication Research Initiative (PCCRI). METHODS: The PCCRI is a multi-site cohort study of naturally occurring inpatient palliative care consultations. The 6-month cohort data includes directly observed and audio-recorded palliative care consultations (up to first 3 visits); patient/proxy/clinician self-report questionnaires both before and the day after consultation; post-consultation in-depth interviews; and medical/administrative records. RESULTS: One hundred fourteen patients or their proxies enrolled in PCCRI during Enrollment Year One (of Three). Seventy percent of eligible patients/proxies were invited to hear about a communication research study (188/269); 60% of them ultimately enrolled in the PCCRI (114/188), resulting in a 42% sampling proportion (114/269 eligible). All PC clinicians at study sites were invited to participate; all 45 participated. CONCLUSIONS: Epidemiologic study of patient-family-clinician communication in palliative care settings is feasible and acceptable to patients, proxies and clinicians. We detail the successful PCCRI methods for enrollment, direct observation and data collection for this complex "field" environment. PMID- 26286541 TI - Response to Letter Regarding Article, "Intracranial Dural Arteriovenous Fistulae: Clinical Presentation and Management Strategies". PMID- 26286540 TI - Periprocedural Myocardial Infarction After Carotid Endarterectomy and Stenting: Systematic Review and Meta-Analysis. AB - BACKGROUND AND PURPOSE: Carotid angioplasty and stenting (CAS) is associated with higher risk of periprocedural stroke and death when compared with carotid endarterectomy (CEA). By contrast, the risk of myocardial infarction (MI) was higher after CEA than after CAS in randomized trials. However, numbers were small, and risk factors are unknown. METHODS: We performed a systematic review and a meta-analysis of studies published from January 1980 to June 2014 and collected unpublished data. We extracted data on 9 predefined risk factors (age, contralateral carotid occlusion, coronary artery disease, diabetes mellitus, sex, hypertension, peripheral artery disease, type stenosis, and clinical presentation). We selected studies with data available on MI in at least 1 subgroup, calculated absolute and relative risks, and identified differential effects on risks of MI. RESULTS: The 30-day absolute risk of MI was 0.87% (95% confidence interval, 0.69-1.07) after CEA and 0.70% (95% confidence interval, 0.54-0.88) after CAS (Pint=0.38). After CAS, patients with symptomatic stenosis and restenosis were at higher risk of MI, whereas men were at lower risk. After CEA, age, history of coronary artery disease, peripheral artery disease, and restenosis increased the risk of MI. Only the effect of sex differed between CAS and CEA with men being at lower risk of MI than women after CAS, whereas there was no difference between after CEA (Pint=0.01). CONCLUSIONS: The risk of MI after CEA and CAS did not significantly differ. Risk factors for MI are overall similar in both techniques except that men are at lower risk of MI after CAS but not after CEA. PMID- 26286543 TI - Letter by Gross and Du Regarding Article, "Intracranial Dural Arteriovenous Fistulae: Clinical Presentation and Management Strategies". PMID- 26286542 TI - Ethnic Differences in Poststroke Quality of Life in the Brain Attack Surveillance in Corpus Christi (BASIC) Project. AB - BACKGROUND AND PURPOSE: Mexican Americans (MAs) have an increased risk of stroke and experience worse poststroke disability than non-Hispanic whites, which may translate into worse poststroke quality of life (QOL). We assessed ethnic differences in poststroke QOL, as well as potential modification of associations by age, sex, and initial stroke severity. METHODS: Ischemic stroke survivors were identified through the biethnic, population-based Brain Attack Surveillance in Corpus Christi (BASIC) Project. Data were collected from medical records, baseline interviews, and 90-day poststroke interviews. Poststroke QOL was measured at ~90 days by the validated short-form stroke-specific QOL in 3 domains: overall, physical, and psychosocial (range, 0-5; higher scores represent better QOL). Tobit regression was used to model associations between ethnicity and poststroke QOL scores, adjusted for demographics, clinical characteristics, and prestroke cognition and function. RESULTS: Among 290 eligible stroke survivors (66% MA, 34% non-Hispanic whites, median age=69 years), median scores for overall, physical, and psychosocial poststroke QOL were 3.3, 3.8, and 2.7, respectively. Poststroke QOL was lower for MAs than non-Hispanic whites both overall (mean difference, -0.30; 95% confidence interval, -0.59, -0.01) and in the physical domain (mean difference, -0.47; 95% confidence interval, -0.81, 0.14) after multivariable adjustment. No ethnic difference was found in the psychosocial domain. Age modified the associations between ethnicity and poststroke QOL such that differences were present in older but not in younger ages. CONCLUSIONS: Disparities exist in poststroke QOL for MAs and seem to be driven by differences in older stroke patients. Targeted interventions to improve outcomes among MA stroke survivors are urgently needed. PMID- 26286545 TI - Genetic Determinants of Unruptured Intracranial Aneurysms in the General Population. AB - BACKGROUND AND PURPOSE: Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) for intracranial aneurysms in clinical samples. In addition, SNPs have been discovered for blood pressure, one of the strongest risk factors for intracranial aneurysms. We studied the role of these genetic variants on occurrence and size of unruptured intracranial aneurysms, discovered incidentally in a general community-dwelling population. METHODS: In 4890 asymptomatic participants from the Rotterdam Study, 120 intracranial aneurysms were identified on brain imaging and segmented for maximum diameter and volume. Genetic risk scores (GRS) were calculated for intracranial aneurysms (10 SNPs), systolic blood pressure (33 SNPs), and diastolic blood pressure (41 SNPs). RESULTS: The GRS for intracranial aneurysms was not statistically significantly associated with presence of aneurysms in this population (OR, 1.16; 95% CI, 0.96 1.40; P=0.119), but showed a significant association with both maximum diameter (difference in log-transformed mm per SD increase of GRS, 0.10; 95% CI, 0.02 0.19; P=0.018) and volume (difference in log-transformed uL per SD increase of GRS, 0.21; 95% CI, 0.01-0.41; P=0.040) of aneurysms. GRSs for blood pressures were associated with neither presence nor size of aneurysms. CONCLUSIONS: Genetic variants previously identified for intracranial aneurysms in clinical studies relate to the size rather than the presence of incidentally discovered, unruptured intracranial aneurysms in the general population. PMID- 26286544 TI - Thirty-Day Outcome of a Multicenter Registry Study of Stenting for Symptomatic Intracranial Artery Stenosis in China. AB - BACKGROUND AND PURPOSE: Although recent trials have suggested that stenting is worse than medical therapy for patients with severe symptomatic intracranial atherosclerotic stenosis, it is not clear whether this conclusion applies to a subset of patients with hypoperfusion symptoms. To justify for a new trial in China, we performed a multicenter prospective registry study to evaluate the safety and efficacy of endovascular stenting within 30 days for patients with severe symptomatic intracranial atherosclerotic stenosis. METHODS: Patients with symptomatic intracranial atherosclerotic stenosis caused by 70% to 99% stenosis combined with poor collaterals were enrolled. The patients were treated either with balloon-mounted stent or with balloon predilation plus self-expanding stent as determined by the operators following a guideline. The primary outcome within 30 days is stroke, transient ischemic attack, and death after stenting. The secondary outcome is successful revascularization. The baseline characteristics and outcomes of the 2 treatment groups were compared. RESULTS: From September 2013 to January 2015, among 354 consecutive patients, 300 patients (aged 58.3+/ 9.78 years) were recruited, including 159 patients treated with balloon-mounted stent and 141 patients with balloon plus self-expanding stent. The 30-day rate of stroke, transient ischemic attack, and death was 4.3%. Successful revascularization was 97.3%. Patients treated with balloon-mounted stent were older, less likely to have middle cerebral artery lesions, more likely to have vertebral artery lesions, more likely to have Mori A lesions, less likely to have Mori C lesions, and likely to have lower degree of residual stenosis than patients treated with balloon plus self-expanding stent. CONCLUSIONS: The short term safety and efficacy of endovascular stenting for patients with severe symptomatic intracranial atherosclerotic stenosis in China is acceptable. Balloon mounted stent may have lower degree of residual stenosis than self-expanding stent. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01968122. PMID- 26286547 TI - Wilson disease: a most unusual patient. PMID- 26286546 TI - Management of Mycoplasma genitalium infections - can we hit a moving target? AB - Mycoplasma genitalium is an etiological agent of sexually transmitted infections, but due to its fastidious growth requirements, only a few M. genitalium strains are available for determination of the activity of currently used and new antimicrobial agents.Recent clinical trials have demonstrated that treatment with azithromycin has decreasing efficacy due to an increasing prevalence of macrolide resistance, which is likely to be attributed to the widespread use of 1 g single dose azithromycin. Second line treatment with moxifloxacin is similarly under pressure from emerging resistance. The era of single dose monotherapy for uncomplicated STIs such as M. genitalium and N. gonorrhoeae, while convenient for patients and physicians, has been associated with escalating resistance and treatment failure and is now drawing to a close. There is a critical need for trials of combinations of existing registered drugs and new antimicrobial compounds, implementation of diagnostic testing combined with molecular detection of resistance, and antimicrobial surveillance. PMID- 26286548 TI - The effect of computer-based cognitive flexibility training on recovery of executive function after stroke: rationale, design and methods of the TAPASS study. AB - BACKGROUND: Stroke survivors frequently suffer from executive impairments even in the chronic phase after stroke, and there is a need for improved rehabilitation of these functions. One way of improving current rehabilitation treatment may be by online cognitive training. Based on a review of the effectiveness of computer based cognitive training in healthy elderly, we concluded that cognitive flexibility may be a key element for an effective training, which results in improvements not merely on trained tasks but also in untrained tasks (i.e., far transfer). The aim of the current study was to track the behavioral and neural effects of computer-based cognitive flexibility training after stroke. We expected that executive functioning would improve after the cognitive flexibility training, and that neural activity and connectivity would normalize towards what is seen in healthy elderly. METHODS/DESIGN: The design was a multicenter, double blind, randomized controlled trial (RCT) with three groups: an experimental intervention group, an active control group who did a mock training, and a waiting list control group. Stroke patients (3 months to 5 years post-stroke) with cognitive complaints were included. Training consisted of 58 half-hour sessions spread over 12 weeks. The primary study outcome was objective executive function. Secondary measures were improvement on training tasks, cognitive flexibility, objective cognitive functioning in other domains than the executive domain, subjective cognitive and everyday life functioning, and neural correlates assessed by both structural and resting-state functional Magnetic Resonance Imaging. The three groups were compared at baseline, after six and twelve weeks of training, and four weeks after the end of the training. Furthermore, they were compared to healthy elderly who received the same training. DISCUSSION: The cognitive flexibility training consisted of several factors deemed important for effects that go beyond improvement on merely the training task themselves. Due to the presence of two control groups, the effects of the training could be compared with spontaneous recovery and with the effects of a mock training. This study provides insight into the potential of online cognitive flexibility training after stroke. We also compared its results with the effectiveness of the same training in healthy elderly. TRIAL REGISTRATION: The Netherlands National Trial Register NTR5174. Registered 22 May 2015. PMID- 26286549 TI - Health literacy in Beijing: an assessment of adults' knowledge and skills regarding communicable diseases. AB - BACKGROUND: There have been a number of studies conducted to date looking at the issue of health literacy, but none have been conducted in Beijing, China. The aim of this study was to evaluate the communicable diseases health literacy (CDHL) levels of Beijing residents towards three key areas: knowledge, adoption of preventative measures/behaviours, and health skills. METHODS: A structured survey was undertaken with Beijing residents aged >=18 years. A multistage stratified sampling approach was used to identify and recruit residents. Participants were excluded if they were foreigners, residents of Hong Kong, Macau or Taiwan, or were unable to communicate in Mandarin. RESULTS: The questionnaire was completed by 11052 participants, with a moderate accuracy rate (average: 61.3 %) and a good discrimination level (average: 0.428). Cronbach's alpha was 0.748. The items were grouped into three subscales representing knowledge, adoption of preventative measures and behaviours, and health skills. Correlations of the subscales and the Total Score is significant (P < 0.01), and all the three subscales correlate strongly with the Total Score The mean CDHL score of Beijing inhabitants was 15.28. The percentage of those who were identified as having adequate CDHL was 41 %. CONCLUSIONS: The total CDHL level of residents in Beijing was relatively low, particularly in those residing in the suburbs, those above 60 years of age, manual workers, and the illiterates. Gender, age-group, level of education, occupation, self-reported health status and region were all shown to be significantly predictive of CDHL. It is important that more resources are dedicated to improving the CDHL in Beijing, given the risk of emerging and re emerging infectious diseases in the region. PMID- 26286550 TI - Pre-existing atrial fibrillation and risk of arterial thromboembolism and death in intensive care unit patients: a population-based cohort study. AB - INTRODUCTION: Pre-existing atrial fibrillation (AF) may worsen prognosis in patients admitted to the intensive care unit (ICU). METHODS: In a cohort study (2005-2011) including all patients with first-time ICU admissions in Denmark (n=57,110), we compared patients with and without pre-existing AF and estimated absolute risks and relative risks (RRs) of arterial thromboembolism and death within 30 days and 365 days following admission, using Kaplan-Meier methods and multivariate regression analyses. We analysed the prognostic impact of AF within strata of patient age, sex, coexisting cardiac diseases, and ICU therapies. RESULTS: Among ICU patients, 5065 (9%) had pre-existing AF. Compared with patients without AF, those with AF were older (median age 75 vs. 62 years) and had more comorbidity. The risk of arterial thromboembolism was 2.8% in patients with AF and 2.0% in non-AF patients at 30 days, and 4.3% and 2.9%, respectively, at 365 days. Corresponding RRs were 1.41 crude and 1.14 (95% confidence interval [CI] 0.93-1.40) adjusted at 30 days, and 1.50 crude and 1.20 (95% CI 1.02-1.41) adjusted at 365 days. Thirty-day mortality was 27% in patients with pre-existing AF and 16% in non-AF patients (crude RR 1.67, adjusted RR 1.04, 95% CI 0.99 1.10). Corresponding mortality estimates at 365 days were 40.9% and 25.4%, respectively (crude RR 1.61, adjusted RR 1.03, 95% CI 1.00-1.07). In stratified analyses, pre-existing AF increased mortality in ICU patients aged <55 years (adjusted RR at 30 days 1.73, 95% CI 1.29-2.32; adjusted RR at 365 days 1.34, 95% CI 1.06-1.69) and in ICU patients treated with mechanical ventilation (adjusted RR at 30 days 1.12, 95% CI 1.05-1.20, adjusted RR at 365 days 1.09, 95% CI: 1.04 1.15). Analyses stratified by sex and coexisting cardiac diseases yielded adjusted RRs close to 1. CONCLUSIONS: In ICU patients, pre-existing AF was associated with modestly increased risk of arterial thromboembolism when adjusted for the substantially higher age and comorbidity levels in patients with AF, whereas there was no overall association with mortality. In ICU patients aged <55 years and in those treated with mechanical ventilation, AF predicted increased mortality. PMID- 26286551 TI - Outcomes after fixation for undisplaced femoral neck fracture compared to hemiarthroplasty for displaced femoral neck fracture among the elderly. AB - BACKGROUND: This study compared the rates of mortality, medical complication, and reoperation after fixation surgery for displaced femoral neck fracture with those after hemiarthroplasty surgery for undisplaced femoral neck fracture using competing risk analysis in inpatients aged 60 years and above from a population database in Taiwan. METHODS: We identified 13,772 subjects who underwent fixation for undisplaced cervical fracture and 13,772 matched controls who underwent hemiarthroplasty for displaced cervical fracture from 1998 to 2007, and followed them up until the end of 2009. The outcomes of patients who received internal fixation for undisplaced fracture and those of patients who received hemiarthroplasty for displaced fracture were compared. RESULTS: The 3-month, 2 year, and 10-year mortality rates were 4.9%, 22.1%, and 67.1% for fixation, and 5.6%, 23.8%, and 71.0% for hemiarthroplasty, respectively. The 3-month, 2-year, and 10-year cumulative incidence rates of the first reoperation were 7.4%, 18.1%, and 27.7% for fixation and 6.3%, 12.0%, and 22.3% for hemiarthroplasty, respectively. The 3-month cumulative incidence rates of the first medical complication were 14.4% for fixation and 15.4% for hemiarthroplasty, respectively. Hemiarthroplasty had a 1.09 times (95% CI: 1.05-1.12) higher hazard ratio for overall death than fixation. However, fixation had a 1.36 times (95% CI: 1.29-1.43) higher subdistribution hazard ratio for first reoperation than hemiarthroplasty after adjusting for gender, age, and comorbidities. CONCLUSIONS: The short-term overall mortality and medical complication rate of fixation for undisplaced fracture were slightly lower than those of hemiarthroplasty for displaced fracture. However, the short-term cumulative incidence of first reoperation after fixation was significantly higher than that for hemiarthroplasty. Further prospective studies or clinical trials based on the competing risk model, and which include important risk factors, are necessary to quantify the adjusted effects more precisely. PMID- 26286552 TI - A cascade computer model for mocrobicide diffusivity from mucoadhesive formulations. AB - BACKGROUND: The cascade computer model (CCM) was designed as a machine-learning feature platform for prediction of drug diffusivity from the mucoadhesive formulations. Three basic models (the statistical regression model, the K nearest neighbor model and the modified version of the back propagation neural network) in CCM operate sequentially in close collaboration with each other, employing the estimated value obtained from the afore-positioned base model as an input value to the next-positioned base model in the cascade. The effects of various parameters on the pharmacological efficacy of a female controlled drug delivery system (FcDDS) intended for prevention of women from HIV-1 infection were evaluated using an in vitro apparatus "Simulant Vaginal System" (SVS). We used computer simulations to explicitly examine the changes in drug diffusivity from FcDDS and determine the prognostic potency of each variable for in vivo prediction of formulation efficacy. The results obtained using the CCM approach were compared with those from individual multiple regression model. RESULTS: CCM significantly lowered the percentage mean error (PME) and enhanced r(2) values as compared with those from the multiple regression models. It was noted that CCM generated the PME value of 21.82 at 48169 epoch iterations, which is significantly improved from the PME value of 29.91% at 118344 epochs by the back propagation network model. The results of this study indicated that the sequential ensemble of the classifiers allowed for an accurate prediction of the domain with significantly lowered variance and considerably reduces the time required for training phase. CONCLUSION: CCM is accurate, easy to operate, time and cost-effective, and thus, can serve as a valuable tool for prediction of drug diffusivity from mucoadhesive formulations. CCM may yield new insights into understanding how drugs are diffused from the carrier systems and exert their efficacies under various clinical conditions. PMID- 26286553 TI - Rhodococcus antrifimi sp. nov., isolated from dried bat dung of a cave. AB - A Gram-reaction-positive, high DNA G+C content, non-motile actinobacterium, strain D7-21T, was isolated from dried bat dung inside a natural cave and its taxonomic status was examined by using a polyphasic approach. The 16S rRNA gene sequence study showed that the isolate belonged to the genus Rhodococcus and formed a cluster with Rhodococcus defluvii (98.98 % gene similarity), Rhodococcus equi (98.62 %) and Rhodococcus kunmingensis (97.66 %). Whole-cell hydrolysates contained meso-diaminopimelic acid, arabinose and galactose as the diagnostic diamino acid and sugars. MK-8(H2) was the predominant menaquinone. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside, an unknown phosphoglycolipid and an unknown glycolipid. Mycolic acids were present. The major fatty acids were C16 : 0, C18 : 1omega9c and 10-methyl C18 : 0. The DNA G+C content was 70.1 mol%. A battery of phenotypic features and DNA-DNA relatedness data support that strain D7-21T ( = KCTC 29469T = DSM 46727T) represents a novel species of the genus Rhodococcus, for which Rhodococcus antrifimi sp. nov. is proposed. PMID- 26286555 TI - Young doctors' preferences for payment systems: the influence of gender and personality traits. AB - OBJECTIVE: Activity-based payment contracts are common among doctors, but to what extent are they preferred? The aim of this paper is to elicit young doctors' preferences for alternative payment systems before they have adapted to an existing system. We examine the existence of gender differences and the extent to which personality traits determine preferences. METHODS: A cross-sectional survey of all final-year medical students and all interns in Norway examined the extent to which preferences for different payment systems depend on gender and personality traits. Data analysis relied on one-way ANOVA and multinomial logistic regression. RESULTS: The current activity-based payment systems were the least preferred, both in hospitals (16.6%) and in general practice (19.7%). The contrasting alternative "fixed salary" achieved similar relative support. Approximately half preferred the hybrid alternative. When certainty associated with a payment system increased, its appeal rose for women and individuals who are less prestige-oriented, risk-tolerant or effort-tolerant. Activity-based systems were preferred among status- and income-oriented respondents. CONCLUSION: The vast majority of young doctors prefer payment systems that are less activity based than the current contracts offered in the Norwegian health service. Recruitment and retention in less prestigious medical specialities might improve if young doctors could choose payment systems corresponding with their diverse preferences. PMID- 26286554 TI - Read clouds uncover variation in complex regions of the human genome. AB - Although an increasing amount of human genetic variation is being identified and recorded, determining variants within repeated sequences of the human genome remains a challenge. Most population and genome-wide association studies have therefore been unable to consider variation in these regions. Core to the problem is the lack of a sequencing technology that produces reads with sufficient length and accuracy to enable unique mapping. Here, we present a novel methodology of using read clouds, obtained by accurate short-read sequencing of DNA derived from long fragment libraries, to confidently align short reads within repeat regions and enable accurate variant discovery. Our novel algorithm, Random Field Aligner (RFA), captures the relationships among the short reads governed by the long read process via a Markov Random Field. We utilized a modified version of the Illumina TruSeq synthetic long-read protocol, which yielded shallow-sequenced read clouds. We test RFA through extensive simulations and apply it to discover variants on the NA12878 human sample, for which shallow TruSeq read cloud sequencing data are available, and on an invasive breast carcinoma genome that we sequenced using the same method. We demonstrate that RFA facilitates accurate recovery of variation in 155 Mb of the human genome, including 94% of 67 Mb of segmental duplication sequence and 96% of 11 Mb of transcribed sequence, that are currently hidden from short-read technologies. PMID- 26286556 TI - High-Polarity Solvents Decreasing the Two-Photon Transition Probability of Through-Space Charge-Transfer Systems - A Surprising In Silico Observation. AB - In the Letter, we address the question as to why larger two-photon absorption cross sections are observed in nonpolar than in polar solvents for through-space charge-transfer (TSCT) systems such as [2,2]-paracyclophane derivatives. In order to answer this question, we have performed ab initio calculations on two well known TSCT systems, namely, a [2.2]-paracyclophane derivative and a molecular tweezer-trinitrofluorinone complex, and found that the two-photon transition probability values of these systems decreases with increasing solvent polarity. To rationalize this result, we have analyzed the role of different optical channels associated with the two-photon process and noticed that, in TSCTs, the interference between the optical channels is mostly destructive and that its magnitude increases with increasing solvent polarity. Moreover, it is also found that a destructive interference may sometimes even become a constructive one in a nonpolar solvent, making the two-photon activity of TSCTs in polar solvents less than that in nonpolar solvents. PMID- 26286557 TI - Electrocatalytic Properties of Nanocrystalline Calcium-Doped Lanthanum Cobalt Oxide for Bifunctional Oxygen Electrodes. AB - Calcium-doped lanthanum cobalt oxide is a promising electrocatalyst for oxygen evolution and oxygen reduction in rechargeable metal-air batteries and water electrolyzers operating with alkaline electrolyte. Nanocrystalline perovskite of composition La0.6Ca0.4CoO3 with a unique cellular internal structure was prepared at 350 degrees C and then annealed in air at progressively higher temperatures in the range of 600-750 degrees C. The samples were characterized by electrochemical techniques and X-ray photoelectron spectroscopy. The area specific electrocatalytic activity for oxygen evolution/oxygen reduction, the oxidation state of cobalt, and the crystallite size increased with annealing temperature, while the Tafel slope remained constant. These trends provide new insights into the role of the cobalt center in oxygen evolution and oxygen reduction, and how preparation conditions can be altered to tune the activity of the cobalt center for electrocatalysis. We expect these findings to guide the design of electrocatalysts for bifunctional oxygen electrodes, in general. PMID- 26286558 TI - Chemical Reaction Evolving on a Droplet. AB - A high-speed camera was used to investigate the early stage of a chemical reaction within a few milliseconds. We focus on the process of color change caused by a droplet containing a pH indicator when impinging on the surface of alkaline solution. Contrary to our expectation, this reaction starts along the equatorial line, and not at the protruding edge of the droplet, where it first touches the reaction partner. Small vertical fingers emerge from the front line within 1.5 ms. The results suggest that the observed deformation of the droplet and heat diffusion play major roles during this early reaction stage. Our investigations contribute to the understanding of short-term transport processes across interfaces, including the onset of unstable behavior of reaction fronts. PMID- 26286559 TI - Charge Separation at the Molecular Monolayer Surface: Observation and Control of the Dynamics. AB - Charge separation dynamics relevant to an electron transfer have been revealed by time- and angle-resolved two-photon photoemission spectroscopy for an n alkanethiolate self-assembled monolayer (SAM) on a Au(111) surface fabricated by a chemical-wet process. The electron was photoexcited into an image potential state located at 3.7 eV above the Fermi level (EF), and it survived well for more than 100 ps on dodecanethiolate (C12)-SAM. The degree of electron separation is precisely controlled by selecting the length of the alkyl chain (C10-C18). We have also evaluated molecular conductivity at the specific electron energy of EF + 3.7 eV. The tunneling decay parameter, beta, was fitted by beta90 K = 0.097 A( 1) and betaRT = 0.13 A(-1). These values were one order smaller than that at around EF by conventional contact probe methods. PMID- 26286560 TI - Controlled, Stepwise Reduction and Band Gap Manipulation of Graphene Oxide. AB - Graphene oxide (GO) has drawn tremendous interest as a tunable precursor in numerous areas, due to its readily manipulable surface. However, its inhomogeneous and nonstoichiometric structure makes achieving chemical control a major challenge. Here, we present a room-temperature based, controlled method for the stepwise reduction of GO, with evidence of sequential removal of each organic moiety. By analyzing signature infrared absorption frequencies, we identify the carbonyl group as the first to be reduced, while the tertiary alcohol takes the longest to be completely removed from the GO surface. Controlled reduction allows for progressive tuning of the optical gap from 3.5 eV down to 1 eV, while XPS spectra show a concurrent increase in the C/O ratio. This study is the first step toward selectively enhancing the chemical homogeneity of GO, thus providing greater control over its structure, and elucidating the order of removal of functional groups and hydrazine-vapor reduction. PMID- 26286561 TI - Neutron Scattering Reveals Enhanced Protein Dynamics in Concanavalin A Amyloid Fibrils. AB - Protein aggregation is one of the most challenging topics in life sciences, and it is implicated in several human pathologies. The nature and the role of toxic species is highly debated, with amyloid fibrils being among the most relevant species for their peculiar structural and functional properties. Protein dynamics and in particular the ability to fluctuate through a large number of conformational substates are closely related to protein function. This Letter focuses on amyloid fibril dynamics, and, to our knowledge, it is the first neutron scattering study on a protein (Concanavalin A) isolated in its fibril state. Our results reveal enhanced atomic fluctuations in amyloid fibrils and indicate that the protein is "softer" in the fibril state with respect to the native and amorphous aggregate states. We discuss this finding in terms of a structural interpretation and suggest that the paradigm ordered structure <-> lower flexibility can be questioned when considering the local fast side-chain protein dynamics. PMID- 26286562 TI - Twin Problems of Interfacial Carbonate Formation in Nonaqueous Li-O2 Batteries. AB - We use XPS and isotope labeling coupled with differential electrochemical mass spectrometry (DEMS) to show that small amounts of carbonates formed during discharge and charge of Li-O2 cells in ether electrolytes originate from reaction of Li2O2 (or LiO2) both with the electrolyte and with the C cathode. Reaction with the cathode forms approximately a monolayer of Li2CO3 at the C-Li2O2 interface, while reaction with the electrolyte forms approximately a monolayer of carbonate at the Li2O2-electrolyte interface during charge. A simple electrochemical model suggests that the carbonate at the electrolyte-Li2O2 interface is responsible for the large potential increase during charging (and hence indirectly for the poor rechargeability). A theoretical charge-transport model suggests that the carbonate layer at the C-Li2O2 interface causes a 10-100 fold decrease in the exchange current density. These twin "interfacial carbonate problems" are likely general and will ultimately have to be overcome to produce a highly rechargeable Li-air battery. PMID- 26286563 TI - Hole Mobility of a Liquid Organic Semiconductor. AB - The first detailed study of charge transport through a liquid organic semiconductor (LOS) is reported with the goal of elucidating the effects of molecular motion on charge transport through molecular liquids. Using a liquid, silyl ether-substituted triarylamine, hole transport mobilities were obtained over a wide range of temperatures above the glass transition temperature of the material. Analysis of this data reveals that molecular motion(s) have a negligible effect on macroscopic charge transport through a molecular liquid. The results strongly resemble transport behavior found in conventional, disordered solids and suggest that silyl ether-substituted LOSs may be good candidates for integration into electronic devices, by those who are familiar with the application of traditional triarylamines, where their unique physical state can or could be exploited. PMID- 26286564 TI - Nucleotide Dynamics at the A-Site Cleft in the Peptidyltransferase Center of H. marismortui 50S Ribosomal Subunits. AB - Resistance mutations to antibiotics targeting rRNA can be far from the drug binding site. Crystallography studies revealed that the antibiotic resistance mutation G2482A (G2447A in E. coli ) in Haloarcula marismortui 50S ribosomes does not directly contact the drug or introduce changes to the ribosomal structure except for losing a potassium ion coordinated to a base triple at the drug binding site. Using molecular dynamics simulations, we tested hypotheses regarding the effects of the G2482A mutation and ion coordination on the conformational dynamics of the 50S ribosome. Simulations show that the mutation enhances conformational fluctuation at the antibiotic binding site, weakens the hydrogen-bonding network, and increases flexibility at the 50S peptidyl transferase center (PTC). Our data supports the view that distant mutations can perturb the dynamic network in the ribosomal PTC, thereby raising the entropic cost of antibiotic binding. These results underscore the importance of considering conformational dynamics in rational drug design. PMID- 26286565 TI - Highly Solvatochromic 7-Aryl-3-hydroxychromones. AB - Introduction of the dialkylaminophenyl group in position 7 of 3-hydroxychromone changes the orientation of the excited-state dipole moment and leads to superior solvatochromic properties (>170 nm emission shift in aprotic media). The excited state intramolecular proton-transfer (ESIPT) reaction of 7-aryl-3 hydroxychromones is almost completely inhibited in most solvents. Methylation of the 3-OH abolishes ESIPT completely and also leads to improved photostability. The probes exhibit a ~100-fold increase in fluorescence intensity and large Stokes shifts upon binding to membranes, reflecting differences in membrane phase and charge by a >40 nm spread in the emission band position. PMID- 26286566 TI - Graphene Interfaced with Biological Cells: Opportunities and Challenges. AB - By interfacing the quantum mechanical properties of nanomaterials with the complex processes in biology, several bio/nano systems have evolved with applications in biosensors, cellular devices, drug delivery, and biophotoluminescence. One recent breakthrough has been the application of graphene, a two-dimensional (2-D) sheet of sp(2) hybridized carbon atoms arranged in a honeycomb lattice, as a sensitive platform for interfacing with biological cells to detect intra- and extracellular phenomena, including cellular excretion and cell membrane's potential modulation. In this Perspective, we discuss the recent results on graphene/cell interfacial devices and the principles defining the modulation of charge-carrier properties in graphene and its derivatives via interaction with cellular membranes. Graphene's high sensitivity in these applications evolves from the pi-carrier cloud confined within an atom-thick layer, quantum-capacitance-induced doping enhancement, closely spaced electronic bands, and a large surface area. We discuss the effect of the electronegativity of the cell wall and the dynamic changes in its chemical potential on doping specific carriers into graphene. Finally, we discuss the challenges and opportunities of graphene-interfaced biocellular systems. PMID- 26286567 TI - Deconvolution and Estimation of Water Diffusion in Sulfonated Polyethersulfone Membranes Using Diffusion-Weighted Inversion Recovery. AB - An NMR method was applied for the deconvolution of specific water in sulfonated polyether sulfone membranes, where sulfonated polyethersulfone is a proton conducting polymer in polymer electrolyte membrane fuel cells. The distribution of (1)H longitudinal relaxation times obtained by the inverse Laplace method was utilized to estimate the volume fraction of proton species as a function of relative humidity (RH). The relaxation time distribution clearly revealed two distinguished peaks on the order of 10(-3) and 10(-2) s, which corresponded to water in the larger and smaller channels for proton transports, respectively. We applied a pulse sequence to understand the water species by diffusion-weighted inversion recovery, which led to individual self-diffusion coefficients for deconvoluted water by using the longitudinal relaxation time. At 30% RH, the diffusion coefficient of water in small-sized channels is greater than that in large-sized channels. On the other hand, the diffusion coefficients of protons with smaller and larger water channels are almost the same at 50, 70, and 90% RH. PMID- 26286568 TI - Charge Separation Propensity of the Coenzyme B12-Tyrosine Complex in Adenosylcobalamin-Dependent Methylmalonyl-CoA Mutase Enzyme. AB - We report the electrophilic Fukui function analysis based on density functional reactivity theory (DFRT) to demonstrate the feasibility of the proton-coupled electron transfer (PCET) mechanism. To characterize the charge propensity of an electron-transfer site other than the proton-acceptor site of the coenzyme B12 tyrosine complex, several structural models (ranging from minimal to actual enzyme scaffolds) have been employed at DFT and QM/MM computations. It is shown, based on the methylmalonyl-CoA mutase (MCM) enzyme that substrate binding plays a significant role in displacing the phenoxyl proton of the tyrosine (Y89), which initiates the electron transfer from Y89 to coenzyme B12. PCET-based enzymatic reaction implies that one electron-reduced form of the AdoCbl cofactor induces the cleavage of the Co-C bond, as an alternative to its neutral analogue, which can assist in understanding the origin of the observed trillion-fold rate enhancement in MCM enzyme. PMID- 26286569 TI - Unravelling the Role of the Compressed Gas on Melting Point of Liquid Confined in Nanospace. AB - Phase behaviors of the liquids in nanospaces are of particular interest to understand the thermodynamics of the liquid on the nanoscale and for their applications that involve the confined systems. However, in many cases, the inconsistent observations of melting point variation for confined liquids are often revealed by different groups. Ionic liquids are a special kind of liquid. Here, by using the merits of the nonvolatile nature of ionic liquids, we realized the encapsulation of ionic liquids inside of mesopores silica oxide nanoparticles with a complete removal of compressed gas under high-vacuum condition; the completely confined ionic liquid formed a crystalline-like phase. It was found that compressed gas plays an important role in changing the melting point of the confined ionic liquid. PMID- 26286571 TI - New Subsections for JPC A/B/C and JPC Letters. PMID- 26286570 TI - Wave Packet Dynamics at an Extended Seam of Conical Intersection: Mechanism of the Light-Induced Wolff Rearrangement. AB - Quantum dynamics calculations on a model surface based on CASPT2//CASSCF calculations are carried out to probe the traversal of a wave packet through an extended seam of conical intersection during the light-induced Wolff rearrangement of diazonaphtoquinone. The reaction is applied in the fabrication of integrated circuits. It consists of nitrogen elimination and ring rearrangement to yield a ketene. After excitation, the wave packet relaxes and reaches the extended seam. A fraction of the wave packet decays to the ground state at a region of the seam connected to a carbene intermediate, while the remaining part decays at a region leading to the ketene. The passage of the wave packet through the extended seam explains the competition between concerted ketene formation and a stepwise mechanism involving a carbene. The two primary photoproducts are formed in the first 100 fs of the simulation, in agreement with recent ultrafast spectroscopy measurements. PMID- 26286572 TI - Emerging Themes in Biophysical Chemistry. PMID- 26286573 TI - Bacterial meningitis in children under 15 years of age in Nepal. AB - BACKGROUND: Bacterial meningitis in children is a life-threatening problem resulting in severe morbidity and mortality. For the prompt initiation of antibacterial therapy, rapid and reliable diagnostic methods are of utmost importance. Therefore, this study was designed to find out the rate of bacterial pathogens of meningitis from suspected cases by performing conventional methods and latex agglutination. METHODS: A descriptive type of study was carried out from May 2012 to April 2013. Cerebrospinal fluid (CSF) specimens from 252 suspected cases of meningitis were subjected for Gram staining, bacterial culture and latex agglutination test. The identification of growth of bacteria was done following standard microbiological methods recommended by American Society for Microbiology. Antibiotic sensitivity testing was done by modified Kirby-Bauer disk diffusion method. RESULTS: From the total 252 suspected cases, 7.2 % bacterial meningitis was revealed by Gram staining and culture methods whereas latex agglutination method detected 5.6 %. Gram-negative organisms contributed the majority of the cases (72.2 %) with Haemophilus influenzae as the leading pathogen for meningitis. Overall, 33.3 % mortality rate was found. CONCLUSIONS: In conclusion, a significant rate of bacterial meningitis was found in this study prompting concern for national wide surveillance. PMID- 26286574 TI - Gastrointestinal localization of metronidazole by a lactobacilli-inspired tetramic acid motif improves treatment outcomes in the hamster model of Clostridium difficile infection. AB - OBJECTIVES: Metronidazole, a mainstay treatment for Clostridium difficile infection (CDI), is often ineffective for severe CDI. Whilst this is thought to arise from suboptimal levels of metronidazole in the colon due to rapid absorption, empirical validation is lacking. In contrast, reutericyclin, an antibacterial tetramic acid from Lactobacillus reuteri, concentrates in the gastrointestinal tract. In this study, we modified metronidazole with reutericyclin's tetramic acid motif to obtain non-absorbed compounds, enabling assessment of the impact of pharmacokinetics on treatment outcomes. METHODS: A series of metronidazole-bearing tetramic acid substituents were synthesized and evaluated in terms of anti-C. difficile activities, gastric permeability, in vivo pharmacokinetics, efficacy in the hamster model of CDI and mode of action. RESULTS: Most compounds were absorbed less than metronidazole in cell-based Caco 2 permeability assays. In hamsters, lead compounds compartmentalized in the colon rather than the bloodstream with negligible levels detected in the blood, in direct contrast with metronidazole, which was rapidly absorbed into the blood and was undetectable in caecum. Accordingly, four leads were more efficacious (P < 0.05) than metronidazole in C. difficile-infected animals. Improved efficacy was not due to an alternative mode of action, as the leads retained the mode of action of metronidazole. CONCLUSIONS: This study provides the clearest empirical evidence that the high absorption of metronidazole lowers treatment outcomes for CDI and suggests a role for the tetramic acid motif for colon-specific drug delivery. This approach also has the potential to lower systemic toxicity and drug interactions of nitroheterocyclic drugs for treating gastrointestine specific diseases. PMID- 26286575 TI - Prevalence and type of drug-drug interactions involving ART in patients attending a specialist HIV outpatient clinic in Kampala, Uganda. AB - OBJECTIVES: Scale-up of HIV services in sub-Saharan Africa has rapidly increased, necessitating evaluation of medication safety in these settings. Drug-drug interactions (DDIs) involving antiretrovirals (ARVs) in sub-Saharan Africa are poorly characterized. We evaluated the prevalence and type of ARV DDIs in Ugandan outpatients and identified the patients most at risk. METHODS: A total of 2000 consecutive patients receiving ARVs at the Infectious Diseases Institute, Kampala were studied. The most recent prescription for each patient was screened for clinically significant DDIs using www.hiv-druginteractions.org. Univariable and multivariable logistic regression were used to identify risk factors for DDIs. A screening tool was developed using significant risk factors and tested in a further 500 patients. RESULTS: Clinically significant DDIs were observed in 374 (18.7%) patients, with a total of 514 DDIs observed. Only 0.2% of DDIs involved a contraindicated combination. Comedications commonly associated with DDIs were antibiotics (4.8% of 2000 patients), anthelmintics (2.2%) and antifungals (3.5%). Patient age, gender, CD4 count and weight did not affect risk of DDIs. In multivariable analysis, the patient factors that independently increased risk of DDIs were two or more comedications (P < 0.0001), a PI-containing ARV regimen (P < 0.0001), use of an anti-infective (P < 0.0001) and WHO clinical stage 3-4 (P = 0.04). A scoring system based on having at least two of these risk factors identified between 75% and 90% of DDIs in a validation cohort. CONCLUSIONS: Significant ARV DDIs occur at similar rates in resource-limited settings and developed countries; however, the comedications frequently causing DDIs differ. Development of tools that are relevant to particular settings should be a priority to assist with prevention and management of DDIs. PMID- 26286576 TI - Differential glatiramer acetate treatment persistence in treatment-naive patients compared to patients previously treated with interferon. AB - BACKGROUND: In the treatment of multiple sclerosis, a change of therapy is considered after treatment failure or adverse events. Although disease modifying drugs' (DMD) efficacy and side effects have been fully analysed in clinical trials, the effects of previous therapy use are less well studied. We aimed to study medication persistence with glatiramer acetate in treatment-naive patients and in patients previously treated with interferon. METHODS: A retrospective study of relapsing-remitting multiple sclerosis patients treated with glatiramer acetate in an MS Unit of a Spanish University Hospital (January 2004--September 2013). Treatment time on glatiramer acetate was studied. Reasons for treatment discontinuation were considered as follows: lack of efficacy, serious adverse event, injection-related side effect, pregnancy and lost to follow-up. Use of prior DMD was registered and analysed. Homogeneity of groups was analysed using Fisher's and Mann-Whitney's tests. The Kaplan Meier method and Cox regression model were used to estimate time to and risk of treatment discontinuation. RESULTS: In total, 155 relapsing-remitting multiple sclerosis patients were treated with glatiramer acetate: 100 treatment-naive patients and 55 treated previously with interferon. At the end of the study, 76 patients (49.0%) continued on glatiramer acetate (with an average treatment time (ATT) of 50.4 months, s.d.32.8) and 50 patients (32.3%) had switched therapy: 27 patients (17.4%) for inefficacy (ATT 29.2 months, s.d.17.5), 20 patients (12.9%) for injection site reactions (ATT 16.5 months, s.d.20.3) and 3 patients (1.9%) after serious adverse events (ATT 15.7 months, s.d.15.1). ATT in our cohort was 39 months (s.d.30.0), median follow-up 34 months. Six months after glatiramer acetate initiation, probability of persisting on GA was 91.4%, 82.5% after 12 months and 72.5% after 2 years. The risk of glatiramer acetate treatment discontinuation was 2.8 [1.7 - 4.8] times greater for treatment-naive patients than for patients treated previously with interferon and this was hardly modified after adjusting for sex and age. CONCLUSIONS: Glatiramer acetate was safe and useful with low rates of serious adverse events and low rates of break-through disease. Injection intolerance proved a major limitation to glatiramer acetate use. Patients who had been previously treated with interferons presented a lower probability of glatiramer acetate discontinuation than treatment-naive patients. PMID- 26286578 TI - China sends in medical teams to cope with casualties of Tianjin blast. PMID- 26286577 TI - Reorienting risk to resilience: street-involved youth perspectives on preventing the transition to injection drug use. AB - BACKGROUND: The Youth Injection Prevention (YIP) project aimed to identify factors associated with the prevention of transitioning to injection drug use (IDU) among street-involved youth (youth who had spent at least 3 consecutive nights without a fixed address or without their parents/caregivers in the previous six months) aged 16-24 years in Metro Vancouver, British Columbia. METHODS: Ten focus groups were conducted by youth collaborators (peer researchers) with street-involved youth (n = 47) from November 2009-April 2010. Audio recordings and focus group observational notes were transcribed verbatim and emergent themes identified by open coding and categorizing. RESULTS: Through ongoing data analysis we identified that youth produced risk and deficiency rather than resiliency-based answers. This enabled the questioning guide to be reframed into a strengths-based guide in a timely manner. Factors youth identified that prevented them from IDU initiation were grouped into three domains loosely derived from the risk environment framework: Individual (fear and self-worth), Social Environment (stigma and group norms - including street entrenched adults who actively discouraged youth from IDU, support/inclusion, family/friend drug use and responsibilities), and Physical/Economic Environment (safe/engaging spaces). Engaging youth collaborators in the research ensured relevance and validity of the study. CONCLUSION: Participants emphasized having personal goals and ties to social networks, supportive family and role models, and the need for safe and stable housing as key to resiliency. Gaining the perspectives of street-involved youth on factors that prevent IDU provides a complementary perspective to risk-based studies and encourages strength-based approaches for coaching and care of at-risk youth and upon which prevention programs should be built. PMID- 26286579 TI - Multilevel thoracic ossification of ligamentum flavum coexisted with/without lumbar spinal stenosis: staged surgical strategy and clinical outcomes. AB - BACKGROUND: Thoracic ossification of ligamentum flavum (TOLF) is a progressively disabling disease. Isolated or continuous TOLF has been frequently reported in literature, however there are very few reports of multilevel or non-continuous TOLF. The purpose of the study was to discuss the surgical strategy of multilevel TOLF and evaluate safety and efficacy of a two-stage operation regimen. METHODS: From October 2007 to May 2014, eleven patients (4 males, 7 females) that underwent two-stage surgery for multilevel spinal stenosis were retrospectively reviewed. The follow-up period lasted at least 12 months. Demographic data, radiological findings as well as operative data were collected. Postoperative functional outcomes evaluated by the modified Japanese Orthopedic Association score (mJOA) and complications were analyzed. RESULTS: The patients ranged in age from 30 to 65 years (average, 50.2 +/- 11.8 years), and comprised 4 men and 7 women. All patients exhibited significant improvements in neurological deficits. The mJOA score improved from a mean of 3.5 +/- 2.2 preoperatively to 4.6 +/- 2.3 before second-stage surgery and to 7.5 +/- 2.2 at final follow-up. The improvement was statistically significant in the average mJOA improvement rate at final follow-up. No staging-related complications were noted in this study. CONCLUSIONS: Staged surgery can effectively achieve neurological functional recovery in patients with multi-segment spinal stenosis in thoracic and lumbar regions, with favorable efficacy and safety. Yet, slight neurological deterioration was observed during the intervals of these two index surgeries. PMID- 26286580 TI - Impact of Time Lapse on ASCP Board of Certification Medical Laboratory Scientist (MLS) and Medical Laboratory Technician (MLT) Examination Scores. AB - BACKGROUND: Research in several professional fields has demonstrated that delays (time lapse) in taking certification examinations may result in poorer performance by examinees. Thirteen states and/or territories require licensure for laboratory personnel. A core component of licensure is passing a certification exam. Also, many facilities in states that do not require licensure require certification for employment or preferentially hire certified individuals. OBJECTIVE: To analyze examinee performance on the American Society for Clinical Pathology (ASCP) Board of Certification (BOC) Medical Laboratory Scientist (MLS) and Medical Laboratory Technician (MLT) certification examinations to determine whether delays in taking the examination from the time of program completion are associated with poorer performance. METHODS: We obtained examination data from April 2013 through December 2014 to look for changes in mean (SD) exam scaled scores and overall pass/fail rates. First-time examinees (MLS: n = 6037; MLT, n = 3920) were divided into 3-month categories based on the interval of time between date of program completion and taking the certification exam. RESULTS: We observed significant decreases in mean (SD) scaled scores and pass rates after the first quarter in MLS and MLT examinations for applicants who delayed taking their examination until the second, third, and fourth quarter after completing their training programs. CONCLUSIONS: Those who take the ASCP BOC MLS and MLT examinations are encouraged to do so shortly after completion of their educational training programs. Delays in taking an exam are generally not beneficial to the examinee and result in poorer performance on the exam. PMID- 26286581 TI - Electron Microscopic Analysis of Surface Inorganic Substances on Oral and Combustible Tobacco Products. AB - Although quantitative trace toxic metal analyses have been performed on tobacco products, little has been published on inorganic particulate constituents on and inside the products. We analyzed these constituents using scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDS). The nature of SEM EDS instrumentation makes it an ideal choice for inorganic particulate analyses and yields relevant information to potential exposures during consumption of oral tobacco products, and possibly as a consequence of smoking. Aluminum silicates, silica and calcium compounds were common inorganic particulate constituents of tobacco products. Aluminum silicates and silica from soil were found on external leaf surfaces. Phytolithic silica, found in the lumen of the plant leaf, is of biogenic origin. Calcium oxalate was also apparently of biogenic origin. Small mineral deposits on tobacco could have health implications. Minerals found on the surfaces of smokeless tobacco products could possibly abrade the oral mucosa and contribute to the oral inflammatory responses observed with smokeless tobacco product use. If micron and sub-micron size calcium particles on cigarette filler were transported in mainstream smoke, they could potentially induce a pulmonary irritant inflammation when inhaled. The transport of aluminum silicate and silica in smoke could potentially also contribute to chronic inflammatory disease. PMID- 26286583 TI - Combined use of antidepressants and NSAIDs: NNT for intracranial haemorrhage. PMID- 26286582 TI - Assessment of water, sanitation, and hygiene practices and associated factors in a Buruli ulcer endemic district in Benin (West Africa). AB - BACKGROUND: Control of neglected tropical diseases (NTDs) requires multiple strategic approaches including water, sanitation and hygiene services (WASH). Buruli ulcer (BU), one of the 17 NTDs, remains a public health issue in Benin particularly in the district of Lalo. The availability of water as well as good hygiene are important for the management of Buruli ulcer particularly in the area of wound care one of the main component of the treatment of BU lesions. Given the growing importance of WASH in controlling NTDs and in order to assess the baseline for future cross-cutting interventions, we report here on the first study evaluating the level of WASH and associated factors in Lalo, one of the most BU-endemic districts in Benin. METHOD: A cross-sectional study was carried to assess WASH practices and associated factors in the district of Lalo. Data were collected from 600 heads of household using structured pretested questionnaire and observations triangulated with qualitative information obtained from in-depth interviews of patients, care-givers and community members. Univariate and multivariate analysis were carried to determine the relationships between the potential associated factors and the sanitation as well as hygiene status. RESULTS: BU is an important conditions in the district of Lalo with 917 new cases detected from 2006 to 2012. More than 49 % of the household surveyed used unimproved water sources for their daily needs. Only 8.7 % of the investigated household had improved sanitation facilities at home and 9.7 % had improved hygiene behavior. The type of housing as an indicator of the socioeconomic status, the permanent availability of soap and improved hygiene practices were identified as the main factors positively associated with improved sanitation status. CONCLUSIONS: In the district of Lalo in Benin, one of the most endemic for BU, the WASH indicators are very low. This study provides baseline informations for future cross-cutting interventions in this district. PMID- 26286585 TI - Stability of metabolically healthy obesity over 8 years: the English Longitudinal Study of Ageing. AB - OBJECTIVE: Metabolically healthy obesity possibly reflects a transitional stage before the onset of metabolic dysfunction, but few studies have characterised this transition. We examined the behavioural and biological characteristics of healthy obese adults that progressed to an unhealthy state over 8 years follow up. METHODS: Participants were 2422 men and women (aged 63.3+/-7.7 years, 44.2% men) from the English Longitudinal Study of Ageing. Obesity was defined as BMI >=30 kg/m(2). Based on blood pressure (BP), HDL-cholesterol, triglycerides, HbA1c and C-reactive protein (CRP) participants were classified as 'healthy' (0 or 1 metabolic abnormality) or 'unhealthy' (>=2 metabolic abnormalities). RESULTS: Over 8 years follow-up, 44.5% of healthy obese subjects had transitioned into an unhealthy state, compared to only 16.6 and 26.2% of healthy normal-weight and overweight adults respectively. Compared with healthy obese adults who remained stable, those who progressed to an unhealthy state were more likely to have high BP (75.0% vs 37.0%, age- and sex-adjusted odds ratio (OR) 8.9, 95% CI 4.7-17.0), high CRP (53.7% vs 17.0%, OR=8.6, 95% CI 4.1-18.0), high HbA1c (46.3% vs 5.9%, OR=13.8, 95% CI 6.1-31.2) and high triglycerides (45.4% vs 11.9%, OR=5.9, 95% CI 2.9-12.0) at follow-up, with excess risk remaining independent of lifestyle factors including self-reported physical activity. Progression to an unhealthy state was also linked with significant gains in waist circumference (B=2.7, 95% CI, 0.5-4.9 cm). CONCLUSION: These data show that a healthy obesity phenotype is relatively unstable. Transition to an unhealthy state is characterised by multiple biological changes that are not fully explained by lifestyle risk factors. PMID- 26286584 TI - Leptin produced by obese adipose stromal/stem cells enhances proliferation and metastasis of estrogen receptor positive breast cancers. AB - INTRODUCTION: The steady increase in the incidence of obesity among adults has been paralleled with higher levels of obesity-associated breast cancer. While recent studies have suggested that adipose stromal/stem cells (ASCs) isolated from obese women enhance tumorigenicity, the mechanism(s) by which this occurs remains undefined. Evidence suggests that increased adiposity results in increased leptin secretion from adipose tissue, which has been shown to increased cancer cell proliferation. Previously, our group demonstrated that ASCs isolated from obese women (obASCs) also express higher levels of leptin relative to ASCs isolated from lean women (lnASCs) and that this obASC-derived leptin may account for enhanced breast cancer cell growth. The current study investigates the impact of inhibiting leptin expression in lnASCs and obASCs on breast cancer cell (BCC) growth and progression. METHODS: Estrogen receptor positive (ER+) BCCs were co cultured with leptin shRNA lnASCs or leptin shRNA obASCs and changes in the proliferation, migration, invasion, and gene expression of BCCs were investigated. To assess the direct impact of leptin inhibition in obASCs on BCC proliferation, MCF7 cells were injected alone or mixed with control shRNA obASCs or leptin shRNA obASCs into SCID/beige mice. RESULTS: ER+ BCCs were responsive to obASCs during direct co-culture, whereas lnASCs were unable to increase ER(+) BCC growth. shRNA silencing of leptin in obASCs negated the enhanced proliferative effects of obASC on BCCs following direct co-culture. BCCs co-cultured with obASCs demonstrated enhanced expression of epithelial-to-mesenchymal transition (EMT) and metastasis genes (SERPINE1, MMP-2, and IL-6), while BCCs co-cultured with leptin shRNA obASCs did not display similar levels of gene induction. Knockdown of leptin significantly reduced tumor volume and decreased the number of metastatic lesions to the lung and liver. These results correlated with reduced expression of both SERPINE1 and MMP-2 in tumors formed with MCF7 cells mixed with leptin shRNA obASCs, when compared to tumors formed with MCF7 cells mixed with control shRNA obASCs. CONCLUSION: This study provides mechanistic insight as to how obesity enhances the proliferation and metastasis of breast cancer cells; specifically, obASC-derived leptin contributes to the aggressiveness of breast cancer in obese women. PMID- 26286586 TI - Safety, pharmacokinetic and pharmacodynamic properties of TV-1106, a long-acting GH treatment for GH deficiency. AB - BACKGROUND: TV-1106 (Teva Pharmaceuticals) is a genetically fused recombinant protein of human GH (hGH) and human serum albumin, in development for treatment of GH deficiency (GHD). TV-1106 is expected to have an extended duration of action compared to daily GH treatment and may enable a reduction in the frequency of injections and improve compliance and quality of life for adults and children requiring GHD therapy. OBJECTIVE: To assess the safety, local tolerability, pharmacokinetics and pharmacodynamics of TV-1106 following single s.c. injections in healthy male volunteers. METHODS: Subjects (n=56) were assigned to one of seven ascending dose groups (3-100 mg) and received either a single dose of TV 1106 (n=6) or placebo (n=2) by s.c. injection. RESULTS: Eighteen subjects reported 43 adverse effects (AEs), which were mild to moderate; no serious AEs (SAEs) occurred. In 50, 70 and 100 mg groups there were mild to moderate increases in heart rate and systolic blood pressure that significantly correlated with higher levels of IGF1. TV-1106 showed pharmacokinetic characteristics of a long-acting hGH as demonstrated by a terminal elimination half-life of 23-35 h, delayed time of peak concentration, and systemic levels seen up to 7 days after dosing. IGF1 levels increased in a dose-dependent manner, before reaching a plateau, with levels above baseline extending beyond 7 days post dose. CONCLUSION: Single administration of TV-1106 up to 100 mg was safe in healthy volunteers. Pharmacokinetics and pharmacodynamics support once-weekly administration in patients with GHD. PMID- 26286587 TI - Study design cannot support link between intracranial haemorrhage, antidepressants, and NSAIDs. PMID- 26286588 TI - Anger Problems Predict Long-Term Criminal Recidivism in Partner Violent Men. AB - The current study investigated the influence of anger problems on partner violent men's long-term response to treatment, as indicated by criminal recidivism during an 8-year period after treatment initiation. Participants were 132 men who presented for treatment services at a community-based domestic violence agency. Results indicated that individuals with extensive anger problems had more charges for general violence (GV) offenses and more ongoing problems with protection orders than did those with Normal Anger (NA) profiles. Examinations of specific anger scales indicated that low Anger Control (LAC) and high Anger Expression predict GV recidivism. These findings indicate that a standard cognitive behavioral treatment program may not adequately reduce the recidivism risk of partner violent men with pronounced anger problems, stress the importance of further research to understand the role of anger problems in partner violence treatment, and highlight the need to develop and evaluate new intervention approaches for partner violent men with serious anger dysregulation. PMID- 26286589 TI - Integrating Tumor and Stromal Gene Expression Signatures With Clinical Indices for Survival Stratification of Early-Stage Non-Small Cell Lung Cancer. AB - BACKGROUND: Accurate survival stratification in early-stage non-small cell lung cancer (NSCLC) could inform the use of adjuvant therapy. We developed a clinically implementable mortality risk score incorporating distinct tumor microenvironmental gene expression signatures and clinical variables. METHODS: Gene expression profiles from 1106 nonsquamous NSCLCs were used for generation and internal validation of a nine-gene molecular prognostic index (MPI). A quantitative polymerase chain reaction (qPCR) assay was developed and validated on an independent cohort of formalin-fixed paraffin-embedded (FFPE) tissues (n = 98). A prognostic score using clinical variables was generated using Surveillance, Epidemiology, and End Results data and combined with the MPI. All statistical tests for survival were two-sided. RESULTS: The MPI stratified stage I patients into prognostic categories in three microarray and one FFPE qPCR validation cohorts (HR = 2.99, 95% CI = 1.55 to 5.76, P < .001 in stage IA patients of the largest microarray validation cohort; HR = 3.95, 95% CI = 1.24 to 12.64, P = .01 in stage IA of the qPCR cohort). Prognostic genes were expressed in distinct tumor cell subpopulations, and genes implicated in proliferation and stem cells portended poor outcomes, while genes involved in normal lung differentiation and immune infiltration were associated with superior survival. Integrating the MPI with clinical variables conferred greatest prognostic power (HR = 3.43, 95% CI = 2.18 to 5.39, P < .001 in stage I patients of the largest microarray cohort; HR = 3.99, 95% CI = 1.67 to 9.56, P < .001 in stage I patients of the qPCR cohort). Finally, the MPI was prognostic irrespective of somatic alterations in EGFR, KRAS, TP53, and ALK. CONCLUSION: The MPI incorporates genes expressed in the tumor and its microenvironment and can be implemented clinically using qPCR assays on FFPE tissues. A composite model integrating the MPI with clinical variables provides the most accurate risk stratification. PMID- 26286590 TI - Comparative effectiveness of psychological treatments for depressive disorders in primary care: network meta-analysis. AB - BACKGROUND: A variety of psychological interventions to treat depressive disorders have been developed and are used in primary care. In a systematic review, we compared the effectiveness of psychological treatments grouped by theoretical background, intensity of contact with the health care professional, and delivery mode for depressed patients in this setting. METHODS: Randomized trials comparing a psychological treatment with usual care, placebo, another psychological treatment, pharmacotherapy, or a combination treatment in adult depressed primary care patients were identified by database searches up to December 2013. We performed both conventional pairwise meta-analysis and network meta-analysis combining direct and indirect evidence. Outcome measures were response to treatment (primary outcome), remission of symptoms, post-treatment depression scores and study discontinuation. RESULTS: A total of 37 studies with 7,024 patients met the inclusion criteria. Among the psychological treatments investigated in at least 150 patients face-to-face cognitive behavioral therapy (CBT; OR 1.80; 95 % credible interval 1.35-2.39), face-to-face counselling and psychoeducation (1.65; 1.27-2.13), remote therapist lead CBT (1.87; 1.38-2.53), guided self-help CBT (1.68; 1.22-2.30) and no/minimal contact CBT (1.53; 1.07 2.17) were superior to usual care or placebo, but not face-to-face problem solving therapy and face-to-face interpersonal therapy. There were no statistical differences between psychological treatments apart from face-to-face interpersonal psychotherapy being inferior to remote therapist-lead CBT (0.60; 0.37-0.95). Remote therapist-led (0.86; 0.21-3.67), guided self-help (0.93; 0.62 1.41) and no/minimal contact CBT (0.85; 0.54-1.36) had similar effects as face-to face CBT. CONCLUSIONS: The limited available evidence precludes a sufficiently reliable assessment of the comparative effectiveness of psychological treatments in depressed primary care patients. Findings suggest that psychological interventions with a cognitive behavioral approach are promising, and primarily indirect evidence indicates that it applies also when they are delivered with a reduced number of therapist contacts or remotely. SYSTEMATIC REVIEW REGISTRATION: 01KG1012 at http://www.gesundheitsforschung-bmbf.de/de/2852.php. PMID- 26286591 TI - Qualitative evaluation of primary care providers experiences of a training programme to offer brief behaviour change counselling on risk factors for non communicable diseases in South Africa. AB - BACKGROUND: The global epidemic of non-communicable disease (NCDs) has been linked with four modifiable risky lifestyle behaviours, namely smoking, unhealthy diet, physical inactivity and alcohol abuse. Primary care providers (PCPs) can play an important role in changing patient's risky behaviours. It is recommended that PCPs provide individual brief behaviour change counselling (BBCC) as part of everyday primary care. This study is part of a larger project that re-designed the current training for PCPs in South Africa, to offer a standardized approach to BBCC based on the 5 As and a guiding style. This article reports on a qualitative sub-study, which explored whether the training intervention changed PCPs perception of their confidence in their ability to offer BBCC, whether they believed that the new approach could overcome the barriers to implementation in clinical practice and be sustained, and their recommendations on future training and integration of BBCC into curricula and clinical practice. METHODS: This was a qualitative study that used verbal feedback from participants at the beginning and end of the training course, and twelve individual in-depth interviews with participants once they had returned to their clinical practice. RESULTS: Although PCP's confidence in their ability to counselling improved, and some thought that time constraints could be overcome, they still reported that understaffing, lack of support from within the facility and poor continuity of care were barriers to counselling. However, the current organisational culture was not congruent with the patient-centred guiding style of BBCC. Training should be incorporated into undergraduate curricula of PCPs for both nurses and doctors, to ensure that counselling skills are embedded from the start. Existing PCPs should be offered training as part of continued professional development programmes. CONCLUSIONS: This study showed that although training changed PCPs perception of their ability to offer BBCC, and increased their confidence to overcome certain barriers to implementation, significant barriers remained. It is clear that to incorporate BBCC into everyday care, not only training, but also a whole systems approach is needed, that involves the patient, provider, and service organisation at different levels. PMID- 26286592 TI - Distribution characteristics of salivary cortisol measurements in a healthy young male population. AB - BACKGROUND: Salivary cortisol has been used in various fields of science as a non invasive biomarker of stress levels. This study offers the normative reference values of cortisol measurement for healthy young males. FINDINGS: Salivary cortisol levels were measured in 267 healthy young males (age: 21.7 +/- 1.5 years) in the early morning on two consecutive days and were analyzed by radioimmunoassay. Frequency distribution analysis was conducted with mean values of the measurements taken on the 2 days. The mean salivary cortisol level was 20.39 +/- 7.74 nmol/l (median: 19.31 nmol/l). The skewness and kurtosis of the distribution of the raw data were 0.72 and 0.68, respectively. They were both improved by a square root transformation but not by a logarithmic transformation. CONCLUSIONS: The skewness of the distribution for salivary cortisol measured in the early morning is considerably smaller than that previously reported from afternoon measurements. A "floor effect" may be an explanation for the difference in the distribution characteristics of salivary cortisol. PMID- 26286593 TI - Effects of sensorimotor training volume on recovery of sensorimotor function in patients following lower limb arthroplasty. AB - BACKGROUND: Sensorimotor function is degraded in patients after lower limb arthroplasty. Sensorimotor training is thought to improve sensorimotor skills, however, the optimal training stimulus with regard to volume, frequency, duration, and intensity is still unknown. The aim of this study, therefore, was to firstly quantify the progression of sensorimotor function after total hip (THA) or knee (TKA) arthroplasty and, as second step, to evaluate effects of different sensorimotor training volumes. METHODS: 58 in-patients during their rehabilitation after THA or TKA participated in this prospective cohort study. Sensorimotor function was assessed using a test battery including measures of stabilization capacity, static balance, proprioception, and gait, along with a self-reported pain and function. All participants were randomly assigned to one of three intervention groups performing sensorimotor training two, four, or six times per week. Outcome measures were taken at three instances, at baseline (pre), after 1.5 weeks (mid) and at the conclusion of the 3 week program (post). RESULTS: All measurements showed significant improvements over time, with the exception of proprioception and static balance during quiet bipedal stance which showed no significant main effects for time or intervention. There was no significant effect of sensorimotor training volume on any of the outcome measures. CONCLUSION: We were able to quantify improvements in measures of dynamic, but not static, sensorimotor function during the initial three weeks of rehabilitation following TKA/THA. Although sensorimotor improvements were independent of the training volume applied in the current study, long-term effects of sensorimotor training volume need to be investigated to optimize training stimulus recommendations. TRIAL REGISTRATION: Clinical trial registration number: DRKS00007894. PMID- 26286594 TI - Relationship of anabolic and catabolic biomarkers with muscle strength and physical performance in older adults: a population-based cross-sectional study. AB - BACKGROUND: Previous studies have found inflammation, growth factors, and androgen signaling pathways all contribute to sarcopenia. However, few studies simultaneously have investigated the association between these potential risk factors and sarcopenia among older people. The aim of the study was to investigate whether elevated levels of inflammatory cytokines combined with low levels of anabolic hormone have a synergy effect on muscle strength and functional decline in older people. METHODS: We designed a cross-sectional study of 1,131 subjects aged 60 years and older. Concentrations of serum C-reactive protein, insulin-like growth factor 1 and dehydroepiandrosteronesulphate were assessed using chemiluminescent immunoassays. Handgrip strength was measured using a dynamometer, and physical performance was assessed using a four-meter gait speed and Timed Up and Go test. We defined poor physical performance as a 4 m gait speed <0.8 m/s or Timed Up and Go test >=13.5 s. RESULTS: After adjustment for potential confounding factors, in multiple linear regression analysis, C reactive protein levels are inversely related to handgrip strength (P <0.01), and in multiple logistic regression analysis, C-reactive protein levels are inversely related to poor physical performance (P for trend <0.05) in males, but not in females. After combining three biomarkers, no significant results were observed between biomarker scores and muscle strength or physical performance. CONCLUSIONS: In older males, higher serum C-reactive protein levels, but not insulin-like growth factor 1 and dehydroepiandrosteronesulphate levels, are independently related to lower muscle strength and poor physical performance. In this study we did not observe that a combination of higher catabolic biomarkers and lower anabolic biomarkers were better predictors for muscle strength and physical performance. PMID- 26286595 TI - Using ultrasound to assess the thickness of the transversus abdominis in a sling exercise. AB - BACKGROUND: Activation of the deep stabilizing trunk muscle transversus abdominis (TrA) is important for trunk stabilization and spine stability. Sling exercises are used for the activation of trunk muscles, therefore we determined the thickness of the TrA in a standardized sling exercise in comparison to rest and abdominal press. Furthermore we propose a standardized measurement method, which can be used to compare relative muscle thickness levels in different exercises. METHODS: The main objective of the study was to assess and to compare the thickness of the TrA during different conditions; resting condition, sling exercise condition (non-voluntary contraction), and abdominal press condition (voluntary contraction) using a non-invasive ultrasound-based measurement method. Ultrasound measurement (USM; 8.9 MHz, B-mode) was employed to measure the thickness of the TrA in twenty healthy volunteers (13 m, 7 f), each one measured three times with breaks of 48 h. On each measurement day, the subjects were measured on three different conditions: resting condition (RC), sling condition (SC), and abdominal press condition (APC). The USM images were analyzed using a custom-made MatLab script, to determine the thickness of the TrA. RESULTS: A two way repeated-measurements ANOVA was performed with a significant effect of the factor condition [F(2,38) = 47.82, p < 0.0001, eta(2) = 0.72], no significant effect of the factor time [F(2.38) = 2.45, p = 0.1, eta(2) = 0.11], and no significant interaction effect [F(4,76) = 0.315, p = 0.867, eta(2) = 0.02]. Statistically corrected post-hoc t-tests revealed significant differences in TrA thickness showing that RC < SC (p < 0.001; eta(2) = 0.19; d = 0.96), SC < APC (p < 0.0001; eta(2) = 0.23; d = 1.10), RC < APC (p < 0.0001; eta(2) = 0.53; d = 2.11). As for the test-retest reliability the intra-class correlation coefficient (ICC) yielded a value of 0.71, 0.54, and 0.29, on the conditions RC, SC, and APC, respectively. CONCLUSIONS: We showed that the investigated sling exercise can be used to significantly increase the TrA thickness, and that the TrA thickness was significantly different on the three conditions (RC, SC, APC) using the ultrasound-based method. PMID- 26286596 TI - Correlation of clinical and physical-technical image quality in chest CT: a human cadaver study applied on iterative reconstruction. AB - BACKGROUND: The first aim of this study was to evaluate the correlation between clinical and physical-technical image quality applied to different strengths of iterative reconstruction in chest CT images using Thiel cadaver acquisitions and Catphan images. The second aim was to determine the potential dose reduction of iterative reconstruction compared to conventional filtered back projection based on different clinical and physical-technical image quality parameters. METHODS: Clinical image quality was assessed using three Thiel embalmed human cadavers. A Catphan phantom was used to assess physical-technical image quality parameters such as noise, contrast-detail and contrast-to-noise ratio (CNR). Both Catphan and chest Thiel CT images were acquired on a multislice CT scanner at 120 kVp and 0.9 pitch. Six different refmAs settings were applied (12, 30, 60, 90, 120 and 150refmAs) and each scan was reconstructed using filtered back projection (FBP) and iterative reconstruction (SAFIRE) algorithms (1,3 and 5 strengths) using a sharp kernel, resulting in 24 image series. Four radiologists assessed the clinical image quality, using a visual grading analysis (VGA) technique based on the European Quality Criteria for Chest CT. RESULTS: Correlation coefficients between clinical and physical-technical image quality varied from 0.88 to 0.92, depending on the selected physical-technical parameter. Depending on the strength of SAFIRE, the potential dose reduction based on noise, CNR and the inverse image quality figure (IQF(inv)) varied from 14.0 to 67.8%, 16.0 to 71.5% and 22.7 to 50.6% respectively. Potential dose reduction based on clinical image quality varied from 27 to 37.4%, depending on the strength of SAFIRE. CONCLUSION: Our results demonstrate that noise assessments in a uniform phantom overestimate the potential dose reduction for the SAFIRE IR algorithm. Since the IQF(inv) based dose reduction is quite consistent with the clinical based dose reduction, an optimised contrast-detail phantom could improve the use of contrast-detail analysis for image quality assessment in chest CT imaging. In conclusion, one should be cautious to evaluate the performance of CT equipment taking into account only physical-technical parameters as noise and CNR, as this might give an incomplete representation of the actual clinical image quality performance. PMID- 26286597 TI - Psychometric evaluation of the Malay version of the Montgomery- Asberg Depression Rating Scale (MADRS-BM). AB - BACKGROUND: This study examines the psychometric properties of the Malay version of the Montgomery-Asberg Depression Rating Scale (MADRS-BM). METHODS: A total of 150 participants with (n = 50) and without depression (n = 100) completed the self-rated version of the Montgomery-Asberg Depression Rating Scale (MADRS-S), the Malay versions of the MADRS-BM, the Beck Depression Inventory-II (BDI-II-M), the General Health Questionnaire-12 (GHQ-12), and the Snaith-Hamilton Pleasure Scale (SHAPS-M). RESULTS: With respect to dimensionality of the MADRS-BM, we obtained one factor solution. With respect to reliability, we found that internal consistency was satisfactory. The scale demonstrated excellent parallel form reliability. The one-week test-retest reliability was good. With respect to validity, positive correlations between the MADRS-BM, BDI-II-M, and the GHQ and negative correlation between the MADRS-BM and SHAPS-M provide initial evidence of MADRS-BM's concurrent validity. After adjusting for age, gender, ethnicity, educational level, and marital status, individuals with depression significantly reported higher MADRS-BM scores than did individuals without depression. Hence, there is additional evidence for concurrent validity of the MADRS-BM. Cut-off score of 4 distinguished individuals with depression from individuals without depression with a sensitivity of 78 % and a specificity of 86 %. CONCLUSIONS: The MADRS-BM demonstrated promising psychometric properties in terms of dimensionality, reliability, and validity that generally justifies its use in routine clinical practice in Malaysia. PMID- 26286598 TI - Burden of herpes zoster: the direct and comorbidity costs of herpes zoster events in hospitalized patients over 50 years in France. AB - BACKGROUND: The objectives of this study were to describe hospital stays related to HZ and to evaluate the direct and indirect cost of hospitalizations due to HZ among patients aged over 50 years. METHODS: The hospitalizations of people aged over 50 years were selected from the French national hospital 2011 database (PMSI) using ICD-10 diagnosis codes for HZ. Firstly, stays with HZ as principal or related diagnostic were described through the patient characteristics, type of hospitalization and the related costs. Secondly, a retrospective case-control analysis was performed on stays with HZ as comorbidity in 5 main hospitalizations causes (circulatory, respiratory, osteo-articular, digestive systems and diabetes) to assess the impact of HZ as co-morbidity on the length of stay, mortality rate and costs. RESULTS: In the first analysis, 2,571 hospital stays were collected (60 % of women, mean age: 76.3 years and mean LOS: 9.5 days). The total health assurance costs were 10,8 M?. Mean cost per hospital stay was 4,206?. In the second analysis, a significant difference in LOS and costs was shown when HZ was associated as comorbidity in other hospitalization's causes. CONCLUSIONS: HZ directly impacts on the hospital cost. When present as comorbidity for other medical reasons, HZ significantly increases the length of hospital stay with subsequent economic burden for the French Health System. PMID- 26286599 TI - Adjusting heterogeneous ascertainment bias for genetic association analysis with extended families. AB - BACKGROUND: In family-based association analysis, each family is typically ascertained from a single proband, which renders the effects of ascertainment bias heterogeneous among family members. This is contrary to case-control studies, and may introduce sample or ascertainment bias. Statistical efficiency is affected by ascertainment bias, and careful adjustment can lead to substantial improvements in statistical power. However, genetic association analysis has often been conducted using family-based designs, without addressing the fact that each proband in a family has had a great influence on the probability for each family member to be affected. METHOD: We propose a powerful and efficient statistic for genetic association analysis that considered the heterogeneity of ascertainment bias among family members, under the assumption that both prevalence and heritability of disease are available. With extensive simulation studies, we showed that the proposed method performed better than the existing methods, particularly for diseases with large heritability. RESULTS: We applied the proposed method to the genome-wide association analysis of Alzheimer's disease. Four significant associations with the proposed method were found. CONCLUSION: Our significant findings illustrated the practical importance of this new analysis method. PMID- 26286600 TI - Identification of apoptosis-related microRNAs and their target genes in myocardial infarction post-transplantation with skeletal myoblasts. AB - BACKGROUND: Skeletal myoblasts (SkMs) has provided a promising treatment for myocardial infarction (MI). Functioning as posttranscriptional regulators, microRNAs (miRNAs) play important roles in cardiac repairment and stem cell regulation. However, the correlation between miRNAs and their targeted genes in SkM cell therapy for MI was not fully understood. METHODS: We explored the cardioprotection by SkMs in infracted rats and determined cardiac functions at 4 weeks. In addition, we compared the expression profiles of miRNAs and mRNAs in post-MI rats with or without SkM cell therapy using microarray. The concordance between miRNA expression and mRNA levels of potential target genes was confirmed by quantitative real-time PCR. RESULTS: Quantitative echocardiography and histology showed improved cardiac function, attenuated heart infarcted area and inhibited cardiomyocyte apoptosis in the SkM group, compared with MI group. We identified that 160 miRNAs were differentially expressed in MI group as compared to the control group and 78 miRNAs were differentially expressed in the SkM treated group as compared to the untreated post-MI. We focused on a novel set of apoptosis-associated miRNAs and their target genes, among which 4 miRNAs (miR-30a 5p, miR-30c-5p, miR-145-5p, miR-140-3p), except one (miR-143-3p), were downregulated in the SkM treated group as compared to the untreated group. Furthermore, we found seven genes including Angptl4, Dpep1, Egr1, Eif5a, Tsc22d3, Irs2 and Cebpb that showed a linear correlation with which miRNAs. CONCLUSIONS: The downregulation of apoptosis-regulatory miRNAs and in turn upregulation of target genes may partially account for rescue effect of SKM therapy for MI. PMID- 26286601 TI - Progesterone Receptor (PGR) gene polymorphism is associated with susceptibility to preterm birth. AB - BACKGROUND: Preterm birth (PTB) is the major cause of death in newborn and the second major cause of death in children less than 5 years old worldwide. Genetic polymorphism has been implicated as a factor for the occurrence of preterm birth. The aim of this study is to evaluate whether polymorphism in the progesterone receptor (PGR) is associated with susceptibility to preterm birth. METHODS: A total of 135 women with preterm and 532 women with term deliveries were genotyped for PGR gene polymorphisms (rs660149, rs471767, rs10895068) using Sequenom MassARRAY platform. RESULTS: The G allele of PGR rs660149 polymorphism was significantly associated with susceptibility to PTB in the Malay women. The odds of G allele occurring among Malay women with preterm delivery was twice that of Malay women with term delivery (OR 2.3, 95 % CI (1.2-4.5, P = 0.011). Alternatively, no significant association was observed between PGR rs660149 polymorphisms and susceptibility to PTB in Chinese and Indian women. CONCLUSIONS: This study shows that variability in the occurrence of PTB across ethnicities in Malaysia is partly due to differences in genetic background. We therefore suggest that in addition to life style and environmental factors, genetic factor should be greatly considered in this population. Prior information on the genetic composition of women may help in the identification and management of women at risk of preterm birth complication. PMID- 26286602 TI - Determinants of consistent condom use among female sex workers in Savannakhet, Lao PDR. AB - BACKGROUND: Female sex workers (FSWs) are a high-risk population for HIV. Correct and consistent use of condoms is the most effective measure for reducing transmission of HIV. Lao PDR is a low HIV-prevalence country, but FSWs have a relatively high HIV prevalence. To be able to make recommendations for condom promotion interventions in Lao PDR it is important to know more about the context specific situation. This study looked at reasons for and associated factors of consistent condom use among FSWs. METHODS: A cross-sectional survey among 258 FSWs in Kaysone Phomvihan district in Savannakhet province was performed. RESULTS: Almost all FSWs had enough condoms (94%), condoms always available (100%) and could always afford condoms (92%). Consistent condom use was 97% with non-regular partners and 60% with regular partners. Almost all respondents (95%) had received information about condoms from the drop-in centre. Stated reasons for consistent condom use were prevention of HIV (94%), STIs (88%) and pregnancy (87%). Most reasons for inconsistent condom use were related to partners not wanting to use condoms because of reduced sexual pleasure. Some FSWs reported that they were physically abused and forced not to use condoms. Shorter time in sex work, higher education and FSW not having regular partners were significantly associated with consistent condom use. CONCLUSIONS: Consistent condom use was very high with non-regular partners, but less frequent with regular partners. The main reason for inconsistent condom use was that the partner did not want to use a condom. Associated factors for consistent condom use were not having regular partners, higher education and shorter time in sex work. Condom promotion programs should include both FSWs and their partners and female condoms should be included in condom intervention efforts. Future studies should investigate the validity of self-reported sexual practices, partners' reasons for inconsistent condom use, risk of violence in sex work and why shorter time in sex work is associated with consistent condom use. PMID- 26286603 TI - Monocyte Phenotype and Polyfunctionality Are Associated With Elevated Soluble Inflammatory Markers, Cytomegalovirus Infection, and Functional and Cognitive Decline in Elderly Adults. AB - Monocytes are mediators of the inflammatory response and include three subsets: classical, intermediate, and nonclassical. Little is known about the phenotypical and functional age-related changes in monocytes and their association with soluble inflammatory biomarkers, cytomegalovirus infection, and functional and mental decline. We assayed the activation ex vivo and the responsiveness to TLR2 and TLR4 agonists in vitro in the three subsets and assessed the intracellular production of IL1-alpha (alpha), IL1-beta (beta), IL-6, IL-8, TNF-alpha, and IL 10 of elderly adults (median 83 [67-90] years old;n= 20) compared with young controls (median 35 [27-40] years old;n= 20). Ex vivo, the elderly adults showed a higher percentage of classical monocytes that expressed intracellular IL1-alpha (p= .001), IL1-beta (p= .001), IL-6 (p= .002), and IL-8 (p= .007). Similar results were obtained both for the intermediate and nonclassical subsets and in vitro. Polyfunctionality was higher in the elderly adults. The functionality ex vivo was strongly associated with soluble inflammatory markers. The activation phenotype was independently associated with the anti-cytomegalovirus IgG levels and with functional and cognitive decline. These data demonstrate that monocytes are key cell candidates for the source of the high soluble inflammatory levels. Our findings suggest that cytomegalovirus infection might be a driving force in the activation of monocytes and is associated with the functional and cognitive decline. PMID- 26286604 TI - Temporal Dynamics of Motor Functioning and Cognitive Aging. AB - BACKGROUND: Because of the possible implications for intervention and thus successful aging, researchers have striven to determine whether the age changes in physical and cognitive functioning are coincident or does functioning in one domain change before, and possibly contribute to, functioning in the other. METHODS: Bivariate dual change score models were applied to four cognitive factors and three motor functioning factors available from 813 adults who participated in the Swedish Adoption/Twin Study of Aging. Participants were aged 50-88 at the first of six waves of testing covering a 19-year follow-up period; 68% participated in at least three waves. RESULTS: Model comparisons indicated dynamic coupling relationships between Balance and Fine Motor factors and the Speed cognitive factor. Decline in motor function precedes decline in performance on processing speed tasks, even though the motor function tasks were not timed. Results indicated possible bidirectional coupling between Fine Motor and Speed. CONCLUSIONS: Combined with other dual change score model analyses of cognition and physical function, a picture is beginning to emerge of the cascade of events that may lead to cognitive aging. PMID- 26286606 TI - Relationship Between Mitochondrial DNA Mutations and Aging. Estimation of Age-at death. AB - Some studies have pointed to the relationship between mitochondrial DNA (mtDNA) mutations and age in different tissues, which are potentially interesting in aging research and in forensic identification because they could help to improve the estimation of age-at-death. The present study aims to evaluate the mutations in mtDNA from dentin and pulp and their relation with age. Healthy erupted third molars were extracted from individuals from two Spanish populations, aged 20-70. When analyzing the amplification of hypervariable region 2 of the mtDNA by real time polymerase chain reaction, a negative strong linear correlation was found between the mtDNA amplification and age in dentin from both populations. In contrast, a significant correlation between mtDNA amplification and age in pulp was not discovered, probably due to the majority of the mitochondria are placed in dentin. A difference in mtDNA damage between these two populations was also detected, indicating the role of ancestry as a component. The findings from this research enrich the current studies related to aging and mitochondrial damage and provide a new quantitative tool for estimating the age-at-death that, in combination with traditional age markers, could improve identification accuracy in forensic cases. PMID- 26286605 TI - Plasma Carotenoids Are Inversely Associated With Dementia Risk in an Elderly French Cohort. AB - BACKGROUND: Although intake of fruits and vegetables has been associated with a decreased risk of dementia, studies focusing on nutrients underlying this association are lacking. Our objective was to analyze the relation between plasma carotenoids and the risk of dementia and Alzheimer's disease (AD) in French elderly community dwellers. METHODS: The study population consisted of 1,092 nondemented older participants, from the Three-City-Bordeaux cohort followed for up to 10 years (range: 1.8-10.8 years, median: 9.5 years). Dementia and AD were diagnosed by a committee of neurologists. The concentration of plasma carotenoids (beta-carotene, alpha-carotene, lycopene, lutein, zeaxanthin, and beta cryptoxanthin) was determined at baseline. Longitudinal analyses of the association between each plasma carotenoid, either crude or expressed as a ratio to plasma lipids (total cholesterol + triglycerides), and the risk of dementia or AD were performed by multivariate Cox models. RESULTS: During follow-up, 199 dementia cases, including 132 AD, occurred. After adjustment for sociodemographic data, diet quality, and clinical variables, including baseline cognitive performances, only higher lutein concentration, considered as a function of plasma lipids, was consistently significantly associated with a decreased risk of all-cause dementia and AD (hazard ratio = 0.808, 95% confidence interval = 0.671 0.973, p = .024 and hazard ratio = 0.759, 95% confidence interval = 0.600-0.960, p = .021, respectively for +1 SD). CONCLUSION: This large cohort of older participants suggests that maintaining higher concentrations of lutein in respect to plasma lipids may moderately decrease the risk of dementia and AD. PMID- 26286607 TI - P16INK4a Positive Cells in Human Skin Are Indicative of Local Elastic Fiber Morphology, Facial Wrinkling, and Perceived Age. AB - Senescent cells are more prevalent in aged human skin compared to young, but evidence that senescent cells are linked to other biomarkers of aging is scarce. We counted cells positive for the tumor suppressor and senescence associated protein p16INK4a in sun-protected upper-inner arm skin biopsies from 178 participants (aged 45-81 years) of the Leiden Longevity Study. Local elastic fiber morphology, facial wrinkles, and perceived facial age were compared to tertiles of p16INK4a counts, while adjusting for chronological age and other potential confounders.The numbers of epidermal and dermal p16INK4a positive cells were significantly associated with age-associated elastic fiber morphologic characteristics, such as longer and a greater number of elastic fibers. The p16INK4a positive epidermal cells (identified as primarily melanocytes) were also significantly associated with more facial wrinkles and a higher perceived age. Participants in the lowest tertile of epidermal p16INK4a counts looked 3 years younger than those in the highest tertile, independently of chronological age and elastic fiber morphology.In conclusion, p16INK4a positive cell numbers in sun protected human arm skin are indicative of both local elastic fiber morphology and the extent of aging visible in the face. PMID- 26286608 TI - Prevalence and Factors Associated With Sarcopenia in Suburb-dwelling Older Chinese Using the Asian Working Group for Sarcopenia Definition. AB - BACKGROUND: Sarcopenia is a common condition in older people. The aim of the present study was to examine the prevalence and factors associated with sarcopenia in an elderly Chinese suburb-dwelling population. METHODS: This study was conducted on 1,069 Chinese suburb-dwelling participants aged >=60 years to evaluate sarcopenia using the Asian Working Group for Sarcopenia criteria. Sociodemographic and behavioral characteristics, as well as medical conditions, were considered independent variables to determine factors associated with sarcopenia using a logistic regression model. RESULTS: The prevalence of sarcopenia was 6.4% in men and 11.5% in women. Age was a significant factor in both sexes. In addition, presence of sarcopenia was inversely associated with BMI for both sexes. The odds ration and 95% confidence interval for factors statistically significantly associated with sarcopenia were 5.04 (1.70-14.89) and 2.36 (1.06-5.25) for diabetes in males and females, respectively; 10.60 (1.75 64.24) for daily consumption of alcohol (daily drinkers), 5.58 (2.13-14.59) for peptic ulcer in female (not statistically significant in males). CONCLUSIONS: The Asian Working Group for Sarcopenia criterion is useful for defining sarcopenia, and our data suggest that the prevalence of sarcopenia in the general elderly suburb-dwelling Chinese population is high. Moreover, we find that high body mass index is inversely associated with the likelihood of being sarcopenic and that several others factors such as diabetes, peptic ulcer, and drinking habits increase the prevalence of sarcopenia. PMID- 26286609 TI - Prevalence and correlates of contraceptive use among female adolescents in Ghana. AB - BACKGROUND: Adolescence is a critical stage in the life course and evidence suggests that even though contraceptive use has been steadily increasing among women in Ghana over the past years, contraceptive prevalence and determinants among female adolescents is quite lacking. This paper examines the prevalence and correlates of contraceptive use among female adolescents in Ghana. METHODS: The paper used data from the 2008 Ghana Demographic and Health survey. Bivariate analysis was carried out to determine the contraceptive prevalence among female adolescents while logistic regression analysis was applied to examine the correlates of female adolescent contraceptive use. RESULTS: The study founded that female adolescent contraceptive use was significantly determined by age of adolescent, education, work status, knowledge of ovulatory cycle, visit of health facility and marital status. CONCLUSIONS: This has implications for adolescent sexual and reproductive health programmes in Ghana. It is therefore essential to intensify girl child education and strengthen the provision of family planning information and services for female adolescents in the country. PMID- 26286611 TI - Construction of All-Carbon Quaternary Centers through Cu-Catalyzed Sequential Carbene Migratory Insertion and Nucleophilic Substitution/Michael Addition. AB - A Cu-catalyzed three-component cross-coupling reaction of terminal alkyne, alpha diazo ester, and alkyl halide has been developed. This transformation involves sequent migratory insertion of copper-carbene and nucleophilic substitution, in which a C(sp)-C(sp(3)) bond and a C(sp(3))-C(sp(3)) bond are formed successively on a carbenic center. Michael addition acceptors can also be employed instead of alkyl halides that enable Michael addition to be an alternative way to build C(sp(3))-C(sp(3)) bond. This transformation represents a highly efficient method for the construction of all-carbon quaternary centers. PMID- 26286610 TI - Topical application of a linoleic acid-ceramide containing moisturizer exhibit therapeutic and preventive benefits for psoriasis vulgaris: a randomized controlled trial. AB - Psoriasis is a chronic skin inflammatory disorder with frequent relapse. Ceramides and their key enzymes are deficient in the lesions, resulting in impaired epidermal permeability barrier, which correlates with disease severity. We evaluated the efficacy of linoleic acid-ceramide moisturizer (LA-Cer) as an adjunctive and preventive therapy for psoriasis vulgaris. 106 patients were randomized into two groups. The control group (C1 ) received Mometasone Furoate 0.1% Cream (MF) while the treatment group (T1 ) was given 0.1% MF in combination with LA-Cer moisturizer. Psoriasis Area and Severity Index (PASI), pruritus, capacitance (CAP), and transepidermal water loss (TEWL) of normal skin and lesion were evaluated at Week 0, 2, 4, 8. Subsequently, T1 patients were randomized for another 1 year. LA-Cer-group (T2 ) maintained the use of moisturizer while control group (C2 ) discontinued. CAPs, TEWLs, PASI were assessed after 1 year. Primary endpoints (PASI-50 at Week 8) revealed superiority of LA-Cer-MF versus MF, less relapse, and rebound in LA-Cer-group than control (C2 ) at Year 1. There were time-by-therapy interaction effect on CAPs, lesional TEWL, and PASI. LA-Cer MF induced higher CAP, an earlier reduction of lesional TEWL and PASI than control (C1 ). CAPs, lesional TEWL, and PASI remained stable in LA-Cer-group. CAPs, lesional TEWL, and PASI were comparable to the baseline levels in control group (C2 ). Topical LA-Cer moisturizer can alleviate psoriasis, and could be a valuable approach for the treatment and prevention of psoriasis. PMID- 26286612 TI - Two-dimensional speckle tracking echocardiography: standardization efforts based on synthetic ultrasound data. AB - AIMS: Speckle tracking echocardiography has already demonstrated its clinical potential. However, its use in routine practice is jeopardized by recent reports on high inter-vendor variability of the measurements. As such, the European Association of CardioVascular Imaging (EACVI) and the American Society of Echocardiography (ASE) set up a standardization task force, which was joined by all manufacturers of echocardiographic equipment as well as by companies offering software solutions only, with the ambition to tackle this problem by standardization and quality assurance (QA). METHODS AND RESULTS: In this study, a first step towards QA of all commercially available tracking solutions based on computer-generated ultrasound images is presented. The accuracy of the products was acceptable with relative errors below 10% and intra-vendor reproducibility within 5%. CONCLUSION: Whether these results can be extrapolated to the clinical setting is the topic of an ongoing study of the EACVI/ASE/Industry Task Force to standardize deformation imaging. This study was an important first step in the development of generally accepted tools for QA of speckle tracking echocardiography. PMID- 26286613 TI - Generic drugs: Review and experiences from South India. AB - The cost of pharmaceuticals, as a percentage of total healthcare spending, has been rising worldwide. This has resulted in strained national budgets and a high proportion of people without access to essential medications. Though India has become a global hub of generic drug manufacturing, the expected benefits of cheaper drugs are not translating into savings for ordinary people. This is in part due to the rise of branded generics, which are marketed at a price point close to the innovator brands. Unbranded generic medicines are not finding their way into prescriptions due to issues of confidence and perception, though they are proven to be much cheaper and comparable in efficacy to branded medicines. The drug inventory of unbranded generic manufacturers fares reasonably when reviewed using the World Health Organization-Health Action International (WHO HAI) tool for analysing drug availability. Also, unbranded generic medicines are much cheaper when compared to the most selling brands and they can bring down the treatment costs in primary care and family practice. We share our experience in running a community pharmacy for an urban health center in the Pathanamthitta district of Kerala State, which is run solely on generic medicines. The drug availability at the community pharmacy was 73.3% when analyzed using WHO-HAI tool and the savings for the final consumers were up to 93.1%, when compared with most selling brand of the same formulation. PMID- 26286615 TI - Retraction: 'Viral pathogenicity determinants are suppressors of transgene silencing in Nicotiana benthamiana'. PMID- 26286614 TI - Factors influencing the implementation of chronic care models: A systematic literature review. AB - BACKGROUND: The increasing prevalence of chronic disease faced by both developed and developing countries is of considerable concern to a number of international organisations. Many of the interventions to address this concern within primary healthcare settings are based on the chronic care model (CCM). The implementation of complex interventions such as CCMs requires careful consideration and planning. Success depends on a number of factors at the healthcare provider, team, organisation and system levels. METHODS: The aim of this systematic review was to systematically examine the scientific literature in order to understand the facilitators and barriers to implementing CCMs within a primary healthcare setting. This review focused on both quantitative and qualitative studies which included patients with chronic disease (cardiovascular disease, chronic kidney disease, chronic respiratory disease, type 2 diabetes mellitus, depression and HIV/AIDS) receiving care in primary healthcare settings, as well as primary healthcare providers such as doctors, nurses and administrators. Papers were limited to those published in English between 1998 and 2013. RESULTS: The search returned 3492 articles. The majority of these studies were subsequently excluded based on their title or abstract because they clearly did not meet the inclusion criteria for this review. A total of 226 full text articles were obtained and a further 188 were excluded as they did not meet the criteria. Thirty eight published peer-reviewed articles were ultimately included in this review. Five primary themes emerged. In addition to ensuring appropriate resources to support implementation and sustainability, the acceptability of the intervention for both patients and healthcare providers contributed to the success of the intervention. There was also a need to prepare healthcare providers for the implementation of a CCM, and to support patients as the way in which they receive care changes. CONCLUSION: This systematic review demonstrated the importance of considering human factors including the influence that different stakeholders have on the success or otherwise of the implementing a CCM. PMID- 26286616 TI - The effects of anti-depressants on depression symptom scores at 12 months follow up in patients with cardiometabolic disease: Results from a large primary care cohort. AB - BACKGROUND: Evidence on the long-term usefulness of anti-depressants in managing depression in cardiometabolic disease is limited. AIM: We examined the effects of anti-depressant prescribing on depressive symptoms at 12 months follow-up in patients with cardiometabolic disease and a positive depression screening result at baseline. DESIGN AND SETTING: We retrospectively reviewed routine UK primary care data for patients with coronary heart disease, diabetes and previous stroke for the year 2008-2009. 35,537 patients with one of the three above diseases underwent depression screening using the Hospital Anxiety and Depression Scale (HADS-D). Of 7080 patients with a positive screening result (HADS-D >= 8), 3933 (55.5%) patients had a repeat HADS-D recorded at 12 months follow-up. METHODS: We compared the change in HADS-D at follow-up and remission rate in those who were prescribed anti-depressants (n = 223) against those who were not (n = 3710). RESULTS: The mean change in HADS-D from baseline, for the nonprescribed group was similar to the reduction observed in patients who were continuously prescribed (n = 93) with anti-depressants during follow-up. Patients who were prescribed intermittently (n = 72) or only one (n = 58) prescription during follow-up had a lower reduction in HADS-D compared to the nonprescribed group. There was no difference in remission rates between continuously prescribed and the nonprescribed group, but remission was lower in patients prescribed intermittently and single prescription. CONCLUSION: Improvement in depressive symptoms in patients with cardiometabolic disease at 12 months was not any better in patients prescribed with anti-depressants compared to the nonprescribed group. The role of anti-depressants in the management of depression in cardiometabolic disease merits further investigation. PMID- 26286617 TI - Disease network of mental disorders in Korea. AB - PURPOSE: Network medicine considers networks among genes, diseases, and individuals. Networks of mental disorders remain poorly understood, despite their high comorbidity. In this study, a network of mental disorders in Korea was constructed to offer a complementary approach to treatment. METHODS: Data on the prevalence and morbidity of mental disorders were obtained from the 2006 and 2011 Korean Epidemiologic Catchment Area Study, including 22 psychiatric disorders. Nodes in the network were disease phenotypes identified by Diagnostic and Statistical Manual of Mental Disorders-IV, and the links connected phenotypes showing significant comorbidity. Odds ratios were used to quantify the distance between disease pairs. Network centrality was analyzed with and without weighting of the links between disorders. Degree centrality was correlated with suicidal behaviors and use of mental health services. RESULTS: In 2011 and 2006, degree centrality was highest for major depressive disorder, followed by nicotine dependence and generalized anxiety disorder (2011) or alcohol dependence (2006). Weighted degree centrality was highest in conversion disorder in both years. CONCLUSIONS: Therefore, major depressive disorder and nicotine dependence are highly connected to other mental disorders in Korea, indicating their comorbidity and possibility of shared biological mechanisms. The use of networks could enhance the understanding of mental disorders to provide effective mental health services. PMID- 26286618 TI - Characterisation of the Cullin-3 mutation that causes a severe form of familial hypertension and hyperkalaemia. AB - Deletion of exon 9 from Cullin-3 (CUL3, residues 403-459: CUL3(Delta403-459)) causes pseudohypoaldosteronism type IIE (PHA2E), a severe form of familial hyperkalaemia and hypertension (FHHt). CUL3 binds the RING protein RBX1 and various substrate adaptors to form Cullin-RING-ubiquitin-ligase complexes. Bound to KLHL3, CUL3-RBX1 ubiquitylates WNK kinases, promoting their ubiquitin-mediated proteasomal degradation. Since WNK kinases activate Na/Cl co-transporters to promote salt retention, CUL3 regulates blood pressure. Mutations in both KLHL3 and WNK kinases cause PHA2 by disrupting Cullin-RING-ligase formation. We report here that the PHA2E mutant, CUL3(Delta403-459), is severely compromised in its ability to ubiquitylate WNKs, possibly due to altered structural flexibility. Instead, CUL3(Delta403-459) auto-ubiquitylates and loses interaction with two important Cullin regulators: the COP9-signalosome and CAND1. A novel knock-in mouse model of CUL3(WT) (/Delta403-459) closely recapitulates the human PHA2E phenotype. These mice also show changes in the arterial pulse waveform, suggesting a vascular contribution to their hypertension not reported in previous FHHt models. These findings may explain the severity of the FHHt phenotype caused by CUL3 mutations compared to those reported in KLHL3 or WNK kinases. PMID- 26286620 TI - Hyperglycemia associated dissociative fugue (organic dissociative disorder) in an elderly. AB - Inadequate glycemic control in patients with diabetes is known to be associated with psychiatric disorders such as depression, anxiety disorder, and cognitive impairment. However, dissociative syndrome has not been reported so far. Here we are reporting a case of repeated dissociative fugue associated with hyperglycemia, in an elderly with type II diabetes. Possible neurobiological mechanism has been discussed. PMID- 26286619 TI - A novel mechano-enzymatic cleavage mechanism underlies transthyretin amyloidogenesis. AB - The mechanisms underlying transthyretin-related amyloidosis in vivo remain unclear. The abundance of the 49-127 transthyretin fragment in ex vivo deposits suggests that a proteolytic cleavage has a crucial role in destabilizing the tetramer and releasing the highly amyloidogenic 49-127 truncated protomer. Here, we investigate the mechanism of cleavage and release of the 49-127 fragment from the prototypic S52P variant, and we show that the proteolysis/fibrillogenesis pathway is common to several amyloidogenic variants of transthyretin and requires the action of biomechanical forces provided by the shear stress of physiological fluid flow. Crucially, the non-amyloidogenic and protective T119M variant is neither cleaved nor generates fibrils under these conditions. We propose that a mechano-enzymatic mechanism mediates transthyretin amyloid fibrillogenesis in vivo. This may be particularly important in the heart where shear stress is greatest; indeed, the 49-127 transthyretin fragment is particularly abundant in cardiac amyloid. Finally, we show that existing transthyretin stabilizers, including tafamidis, inhibit proteolysis-mediated transthyretin fibrillogenesis with different efficiency in different variants; however, inhibition is complete only when both binding sites are occupied. PMID- 26286621 TI - Does age predict outcome after multiligament knee reconstruction for the dislocated knee? 2- to 22-year follow-up. AB - PURPOSE: The purpose of this study is to determine whether age is a predictor of clinical and functional outcomes in patients who sustained a knee dislocation (KD) and underwent multiligament knee reconstruction. It was hypothesized that increasing age will negatively affect patient outcome. METHODS: In total, 125 multiligament knee injuries (MLKI) associated with KD were surgically reconstructed between 1992 and 2013 and evaluated with IKDC and Lysholm scores at a median follow-up of 5 (range 2-22) years. Patient demographics including age were then analysed with respect to IKDC and Lysholm scores using rank sums and pair-wise rank sums analysis for continuous variables and Chi-square analysis for categorical variables. RESULTS: In total, 125 patients (96 males and 29 females) with a median age of 31 (range 11-62) years at the time of surgery were included. At final follow-up, patients <=30 years old compared to >30 years old obtained higher IKDC (73.3 vs. 61.9; p = 0.01) and Lysholm scores (76.9 vs. 68.5; p = 0.04). No confounding variables including gender, injury mechanism, injury pattern, injuries to the peroneal nerve, popliteal artery, meniscus, or cartilage accounted for differences in outcome scores between the two groups. CONCLUSION: Based on current available literature, this study represents the largest cohort with the longest follow-up reported on MLKI to date. At intermediate- to long term follow-up, patients >30 years of age that undergo multiligament knee reconstruction for KD have inferior IKDC and Lysholm scores compared to those <=30 years of age. However, successful multiligament knee reconstruction can still be obtained in this age group. LEVEL OF EVIDENCE: IV. PMID- 26286623 TI - Diurnal gene expression of lipolytic natriuretic peptide receptors in white adipose tissue. AB - Disruption of the circadian rhythm can lead to obesity and cardiovascular disease. In white adipose tissue, activation of the natriuretic peptide receptors (NPRs) stimulates lipolysis. We have previously shown that natriuretic peptides are expressed in a circadian manner in the heart, but the temporal expression profile of their cognate receptors has not been examined in white adipose tissue. We therefore collected peri-renal white adipose tissue and serum from WT mice. Tissue mRNA contents of NPRs - NPR-A and NPR-C, the clock genes Per1 and Bmal1, and transcripts involved in lipid metabolism were quantified at 4-h intervals: in the diurnal study, mice were exposed to a period of 12 h light followed by 12 h darkness (n=52). In the circadian study, mice were kept in darkness for 24 h (n=47). Concomitant serum concentrations of free fatty acids, glycerol, triglycerides (TGs), and insulin were measured. Per1 and Bmal1 mRNA contents showed reciprocal circadian profiles (P<0.0001). NPR-A mRNA contents followed a temporal pattern (P=0.01), peaking in the dark (active) period. In contrast, NPR C mRNA was expressed in an antiphase manner with nadir in the active period (P=0.007). TG concentrations in serum peaked in the active dark period (P=0.003). In conclusion, NPR-A and NPR-C gene expression is associated with the expression of clock genes in white adipose tissue. The reciprocal expression may thus contribute to regulate lipolysis and energy homeostasis in a diurnal manner. PMID- 26286622 TI - Continuous passive motion and its effects on knee flexion after total knee arthroplasty in patients with knee osteoarthritis. AB - PURPOSE: This study evaluated the effects of continuous passive motion (CPM) on accelerated flexion after total knee arthroplasty (TKA) and whether CPM application measures (i.e. initial angle and daily increment) are associated with functional outcomes. METHODS: A retrospective investigation was conducted at the rehabilitation centre of a university-based teaching hospital. Patients who received CPM therapy immediately after TKA surgery were categorized into rapid-, normal-, and slow-progress groups according to their response to CPM during their acute inpatient stay. Knee pain, passive knee flexion, and knee function-measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were assessed preoperatively at discharge and at 3- and 6-month outpatient follow up visits. RESULTS: A total of 354 patients were followed for 6 months after inpatient-stay discharge. The patients in the rapid-progress group (n = 119) exhibited significantly greater knee flexions than those in the slow-progress group did (n = 103) at the 3-month follow-up [mean difference (MD) = 10.3 degrees , 95 % confidence interval (CI) 4.3 degrees -16.3 degrees , p < 0.001] and 6 month follow-up (MD = 10.9 degrees , 95 % CI 6.3 degrees -15.6 degrees , p < 0.001). Significant WOMAC score differences between the rapid- and slow-progress groups were observed at the 3-month follow-up (MD = 7.2, 95 % CI 5.4-9.1, p < 0.001) and 6-month follow-up (MD = 16.1, 95 % CI 13.4-18.7, p < 0.001). CPM initial angles and rapid progress significantly predicted short- and long-term outcomes in knee flexion and WOMAC scores (p < 0.001). CONCLUSION: When CPM is used, early application with initial high flexion and rapid progress benefits knee function up to 6 months after TKA. LEVEL OF EVIDENCE: II. PMID- 26286624 TI - Development of a cloud-based application for the Fracture Liaison Service model of care. AB - The aims of this study are to develop a cloud-based application of the Fracture Liaison Service for practitioners to coordinate the care of osteoporotic patients after suffering primary fractures and provide a performance feedback portal for practitioners to determine quality of care. The application provides continuity of care, improved patient outcomes, and reduced medical costs. INTRODUCTION: The purpose of this study is to describe the content development and functionality of a cloud-based application to broadly deploy the Fracture Liaison Service (FLS) to coordinate post-fracture care for osteoporotic patients. METHODS: The Bone Health Collaborative developed the FLS application in 2013 to support practitioners' access to information and management of patients and provide a feedback portal for practitioners to track their performance in providing quality care. A five step protocol (identify, inform, initiate, investigate, and iterate) organized osteoporotic post-fracture care-related tasks and timelines for the application. A range of descriptive data about the patient, their medical condition, therapies and care, and current providers can be collected. Seven quality of care measures from the National Quality Forum, The Joint Commission, and the Centers for Medicare and Medicaid Services can be tracked through the application. RESULTS: There are five functional areas including home, tasks, measures, improvement, and data. The home, tasks, and data pages are used to enter patient information and coordinate care using the five-step protocol. Measures and improvement pages are used to enter quality measures and provide practitioners with continuous performance feedback. The application resides within a portal, running on a multitenant, private cloud-based Avedis enterprise registry platform. All data are encrypted in transit and users access the application using a password from any common web browser. CONCLUSION: The application could spread the FLS model of care across the US health care system, provide continuity of care, effectively manage osteoporotic patients, improve outcomes, and reduce medical costs. PMID- 26286625 TI - Natural history, reasons for, and impact of low/non-adherence to medications for osteoporosis in a cohort of community-dwelling older women already established on medication: a 2-year follow-up study. AB - Approximately 15 % of older women on oral medications for osteoporosis could be considered for alternatives including parenteral therapies. Collection of data on socio-demographic/clinical variables is unlikely to be helpful in predicting low/non-adherence. Alternative approaches are needed to identify individuals at risk of low/non-adherence. INTRODUCTION: This study aims to identify individual patient reasons for stopping medications for osteoporosis, and to investigate whether this can be predicted from knowledge about socio-demographic/clinical data, or whether alternative approaches need to be used. METHODS: The Cohort for Skeletal Health in Bristol and Avon (COSHIBA) recruited 3200 older women from South West UK, of whom a proportion were on medications for osteoporosis at baseline. Information on self-reported adherence and reasons for low/non adherence were collected at 6-monthly intervals over a 2-year period. Data was also collected on potential predictors of and impact of low/non-adherence. RESULTS: Two hundred thirty-three of 3200 (7.3 %) women were on medications for osteoporosis at baseline. Mean length of time on treatment prior to enrolment was 46 months. Of those on osteoporosis medications, 94.9 % were on bisphosphonates; 8.5 % reported low adherence and 21.6 % stopped their medication completely over the 2-year follow-up period. Length of time on medication at baseline did not influence rates of low/non-adherence. Reasons for low/non-adherence to bisphosphonates included side effects (53.9 %), practical reasons such as forgetting to take them (18.0 %) and beliefs about medications (20.5 %). No convincing predictors of low/non-adherence were identified. CONCLUSIONS: Approximately 15 % of older women on oral medications for osteoporosis could be considered for alternatives including parenteral therapies. This has important implications for healthcare provision. Collection of data on socio demographic/clinical variables is unlikely to be helpful in predicting low/non adherence. Alternative approaches are needed to identify individuals at risk of low/non-adherence to osteoporosis medications. PMID- 26286626 TI - Impact of hip fracture on hospital care costs: a population-based study. AB - Using a large cohort of hip fracture patients, we estimated hospital costs to be L14,163 and L2139 in the first and second year following fracture, respectively. Second hip and non-hip fractures were major cost drivers. There is a strong economic incentive to identify cost-effective approaches for hip fracture prevention. INTRODUCTION: The purpose of this study was to estimate hospital costs of hip fracture up to 2 years post-fracture and compare costs before and after the index fracture. METHODS: A cohort of patients aged over 60 years admitted with a hip fracture in a UK region between 2003 and 2013 were identified from hospital records and followed until death or administrative censoring. All hospital records were valued using 2012/2013 unit costs, and non-parametric censoring methods were used to adjust for censoring when estimating average annual costs. A generalised linear model examined the main predictors of hospital costs. RESULTS: A cohort of 33,152 patients with a hip fracture was identified (mean age 83 years (SD 8.2). The mean censor-adjusted 1- and 2-year hospital costs after index hip fracture were L14,163 (95 % confidence interval (CI) L14,008 to L14,317) and L16,302 (95 % CI L16,097 to L16,515), respectively. Index admission accounted for 61 % (L8613; 95 % CI L8565 to L8661) of total 1-year hospital costs which were L10,964 higher compared to the year pre-event (p < 0.001). The main predictors of 1-year hospital costs were second hip fracture, other non-hip fragility fractures requiring hospitalisation and hip fracture related complications. Total UK annual hospital costs associated with incident hip fractures were estimated at L1.1 billion. CONCLUSIONS: Hospital costs following hip fracture are high and mostly occur in the first year after the index hip fracture. Experiencing a second hip fracture after the index fracture accounted for much of the increase in costs. There is a strong economic incentive to prioritise research funds towards identifying the best approaches to prevent both index and subsequent hip fractures. PMID- 26286627 TI - Validity of parental recall of children's fracture: implications for investigation of childhood osteoporosis. AB - Fracture history is an important component of osteoporosis diagnosis in children. One in six parentally reported lifetime fractures in children were not confirmed on review of radiographs. Care should be taken to avoid unnecessary investigations for possible osteoporosis due to parental over-reporting of soft tissue injuries as fractures. INTRODUCTION: The diagnosis of osteoporosis in children requires either a vertebral compression fracture, or a significant fracture history (defined as >=2 long bone fractures <10 years or >=3 long bone fractures <19 years, excluding high impact fractures) and low bone mineral density. As children with frequent fractures might benefit from further evaluation, we determined whether parental reports of lifetime fracture were accurate compared to radiological reports and if they appropriately selected children for further consideration of osteoporosis. METHODS: Parents of children (<18 years) with a musculoskeletal injury completed a questionnaire on their child's fracture history, including age, site and mechanism of previous fracture(s). Radiological reports were reviewed to confirm the fracture. RESULTS: Six hundred sixty parents completed the questionnaire and reported 276 previous fractures in 207 children. An injury treated at our hospital was recorded in 214 of the 276 parentally reported fractures. Thirty-four of 214 (16 %) were not a confirmed fracture. An injury was recorded for all parentally reported fractures in 150 children, but for 21 % children, there were inaccurate details (no evidence of fracture, incorrect site or forgotten fractures) on parent report. Eighteen of 150 children had a significant fracture history on parental report alone, but following review of radiology reports, 2 of 18 (11 %) did not have clinically significant fracture histories. CONCLUSIONS: Approximately one in six fractures reported by parents to have occurred in their child's lifetime had not resulted in a fracture. One in nine children with a significant fracture history could have been investigated unnecessarily. PMID- 26286628 TI - Complexity of cardiac signals for predicting changes in alpha-waves after stress in patients undergoing cardiac catheterization. AB - The hierarchical interaction between electrical signals of the brain and heart is not fully understood. We hypothesized that the complexity of cardiac electrical activity can be used to predict changes in encephalic electricity after stress. Most methods for analyzing the interaction between the heart rate variability (HRV) and electroencephalography (EEG) require a computation-intensive mathematical model. To overcome these limitations and increase the predictive accuracy of human relaxing states, we developed a method to test our hypothesis. In addition to routine linear analysis, multiscale entropy and detrended fluctuation analysis of the HRV were used to quantify nonstationary and nonlinear dynamic changes in the heart rate time series. Short-time Fourier transform was applied to quantify the power of EEG. The clinical, HRV, and EEG parameters of postcatheterization EEG alpha waves were analyzed using change-score analysis and generalized additive models. In conclusion, the complexity of cardiac electrical signals can be used to predict EEG changes after stress. PMID- 26286629 TI - Performance evaluation of indel calling tools using real short-read data. AB - BACKGROUND: Insertion and deletion (indel), a common form of genetic variation, has been shown to cause or contribute to human genetic diseases and cancer. With the advance of next-generation sequencing technology, many indel calling tools have been developed; however, evaluation and comparison of these tools using large-scale real data are still scant. Here we evaluated seven popular and publicly available indel calling tools, GATK Unified Genotyper, VarScan, Pindel, SAMtools, Dindel, GTAK HaplotypeCaller, and Platypus, using 78 human genome low coverage data from the 1000 Genomes project. RESULTS: Comparing indels called by these tools with a known set of indels, we found that Platypus outperforms other tools. In addition, a high percentage of known indels still remain undetected and the number of common indels called by all seven tools is very low. CONCLUSION: All these findings indicate the necessity of improving the existing tools or developing new algorithms to achieve reliable and consistent indel calling results. PMID- 26286630 TI - Less is more: Avoiding the LIBS dimensionality curse through judicious feature selection for explosive detection. AB - Despite its intrinsic advantages, translation of laser induced breakdown spectroscopy for material identification has been often impeded by the lack of robustness of developed classification models, often due to the presence of spurious correlations. While a number of classifiers exhibiting high discriminatory power have been reported, efforts in establishing the subset of relevant spectral features that enable a fundamental interpretation of the segmentation capability and avoid the 'curse of dimensionality' have been lacking. Using LIBS data acquired from a set of secondary explosives, we investigate judicious feature selection approaches and architect two different chemometrics classifiers -based on feature selection through prerequisite knowledge of the sample composition and genetic algorithm, respectively. While the full spectral input results in classification rate of ca.92%, selection of only carbon to hydrogen spectral window results in near identical performance. Importantly, the genetic algorithm-derived classifier shows a statistically significant improvement to ca. 94% accuracy for prospective classification, even though the number of features used is an order of magnitude smaller. Our findings demonstrate the impact of rigorous feature selection in LIBS and also hint at the feasibility of using a discrete filter based detector thereby enabling a cheaper and compact system more amenable to field operations. PMID- 26286631 TI - On the transmission pattern of Kyasanur Forest disease (KFD) in India. AB - Kyasanur Forest disease (KFD), a tick-borne viral hemorrhagic fever, is endemic in five districts of Karnataka state, India. Recent reports of the spread of disease to neighboring districts of the Western Ghats, namely Chamarajanagar district in Karnataka, Nilgiri district in Tamil Nadu, Wayanad and Malappuram districts in Kerala, and Pali village in Goa are a cause for concern. Besides vaccination of the affected population, establishing an event-based surveillance system for monkey deaths in the national parks, wildlife sanctuaries and reserve forests of the Western Ghats would help detect the disease early and thereby help implement appropriate control measures. PMID- 26286632 TI - Elevated expression of mechanosensory polycystins in human carotid atherosclerotic plaques: association with p53 activation and disease severity. AB - Atherosclerotic plaque formation is associated with irregular distribution of wall shear stress (WSS) that modulates endothelial function and integrity. Polycystins (PC)-1/-2 constitute a flow-sensing protein complex in endothelial cells, able to respond to WSS and induce cell-proliferation changes leading to atherosclerosis. An endothelial cell-culture system of measurable WSS was established to detect alterations in PCs expression under conditions of low- and high-oscillatory shear stress in vitro. PCs expression and p53 activation as a regulator of cell proliferation were further evaluated in vivo and in 69 advanced human carotid atherosclerotic plaques (AAPs). Increased PC-1/PC-2 expression was observed at 30-60 min of low shear stress (LSS) in endothelial cells. Elevated PC 1 expression at LSS was followed by p53 potentiation. PCs immunoreactivity localizes in areas with macrophage infiltration and neovascularization. PC-1 mRNA and protein levels were significantly higher than PC-2 in stable fibroatherotic (V) and unstable/complicated (VI) AAPs. Elevated PC-1 immunostaining was detected in AAPs from patients with diabetes mellitus, dyslipidemia, hypertension and carotid stenosis, at both arteries (50%) or in one artery (90%). PCs seem to participate in plaque formation and progression. Since PC-1 upregulation coincides with p38 and p53 activation, a potential interplay of these molecules in atherosclerosis induction is posed. PMID- 26286633 TI - A Nucleus-Imaging Probe That Selectively Stabilizes a Minor Conformation of c-MYC G-quadruplex and Down-regulates c-MYC Transcription in Human Cancer Cells. AB - The c-MYC proto-oncogene is a regulator of fundamental cellular processes such as cell cycle progression and apoptosis. The development of novel c-MYC inhibitors that can act by targeting the c-MYC DNA G-quadruplex at the level of transcription would provide potential insight into structure-based design of small molecules and lead to a promising arena for cancer therapy. Herein we report our finding that two simple bis-triazolylcarbazole derivatives can inhibit c-MYC transcription, possibly by stabilizing the c-MYC G-quadruplex. These compounds are prepared using a facile and modular approach based on Cu(I) catalysed azide and alkyne cycloaddition. A carbazole ligand with carboxamide side chains is found to be microenvironment-sensitive and highly selective for "turn-on" detection of c-MYC quadruplex over duplex DNA. This fluorescent probe is applicable to visualize the cellular nucleus in living cells. Interestingly, the ligand binds to c-MYC in an asymmetric fashion and selects the minor populated conformer via conformational selection. PMID- 26286634 TI - Neural evidence for moral intuition and the temporal dynamics of interactions between emotional processes and moral cognition. AB - Behavioral and neurological studies have revealed that emotions influence moral cognition. Although moral stimuli are emotionally charged, the time course of interactions between emotions and moral judgments remains unknown. In the present study, we investigated the temporal dynamics of the interaction between emotional processes and moral cognition. The results revealed that when making moral judgments, the time course of the event-related potential (ERP) waveform was significantly different between high emotional arousal and low emotional arousal contexts. Different stages of processing were distinguished, showing distinctive interactions between emotional processes and moral reasoning. The precise time course of moral intuition and moral reasoning sheds new light on theoretical models of moral psychology. Specifically, the N1 component (interpreted as representing moral intuition) did not appear to be influenced by emotional arousal. However, the N2 component and late positive potential were strongly affected by emotional arousal; the slow wave was influenced by both emotional arousal and morality, suggesting distinct moral processing at different emotional arousal levels. PMID- 26286635 TI - Imaging of metastatic clear cell renal cell carcinoma with PSMA-targeted 18F DCFPyL PET/CT. AB - OBJECTIVE: Molecular imaging with positron emission tomography (PET) provides a powerful means of identifying and characterizing cancerous processes, as well as providing a quantitative framework within which response to therapy can be ascertained. Unfortunately, the most commonly used PET radiotracer, 18F fluorodeoxyglucose (FDG), has not demonstrated a definitive role in determining response to therapy in metastatic renal cell carcinoma (RCC). As a result, new radiotracers able to reliably image RCC could be of tremendous value for this purpose. METHODS: Five patients with known metastatic RCC were imaged with the low-molecular weight radiotracer 18F-DCFPyL, an inhibitor of the prostate specific membrane antigen at 60 min post injection. 18F-DCFPyL PET/CT and conventional images (either contrast-enhanced computed tomography or magnetic resonance imaging) were centrally reviewed for suspected sites of disease. RESULTS: In all five patients imaged, sites of putative metastatic disease were readily identifiable by abnormal 18F-DCFPyL uptake, with overall more lesions detected than on conventional imaging. These PET-detected sites included lymph nodes, pancreatic parenchymal lesions, lung parenchymal lesions, a brain parenchymal lesion, and other soft tissue sites. 18F-DCFPyL uptake ranged from subtle to intense with maximum standardized uptake values (SUVmax) for the identified lesions of 1.6-19.3. Based upon this small patient series, limited pathology and imaging follow-up of these patients suggests a higher sensitivity for 18F-DCFPyL compared to conventional imaging in the detection of metastatic RCC (94.7 versus 78.9%). CONCLUSIONS: PSMA expression in the tumor neovasculature of RCC has been previously established and is believed to provide the basis for the imaging findings presented here. PSMA-based PET/CT with radiotracers such as 18F-DCFPyL may allow more accurate staging of patients with RCC and conceivably the ability to predict and follow therapy in patients treated with agents targeting the neovasculature. PMID- 26286637 TI - Perineural invasion in prostate biopsy specimens is associated with increased bone metastasis in prostate cancer. AB - BACKGROUND: We aimed to evaluate the relationship between perineural invasion (PNI) and bone metastasis in prostate cancer (PCa). METHODS: We retrospectively reviewed the data of 633 PCas who had whole-body bone scan (WBBS) between 2008 and 2014. We recorded the age, clinical T-stage, total PSA (tPSA) prior to biopsy, Gleason sum (GS), and PNI in transrectal ultrasound guided biopsy (TRUS Bx) and digital rectal examination findings. Bone metastases were assessed with WBBS and magnetic resonance image if WBBS was suspicious. We divided the patients into two groups according to NCCN criteria: (Group 1) bone scan not indicated, (Group 2) bone scan indicated. RESULTS: There were 262 patients in Group 1 and 371 in 2. There is not significant relationship between PNI and bone metastasis in Group 1. However, there is very limited number of metastatic patients (n = 12) in this group. There is a strong relationship between PNI and bone metastasis in Group 2 (P = 0.001). Sensitivity, specificity and positive predictive value of PNI for bone metastasis were 72.4%, 81.7%, and 77.7%, respectively. In this group, tPSA, GS, positive DRE, and PNI were significant covariates for prediction of bone metastasis in univariate and multivariate analysis (except age). The most powerful predictor was PNI, and it increased the risk of bone metastasis 11-fold. CONCLUSIONS: PNI in the TRUS-Bx specimens is the most powerful predictive histopathological feature for bone metastasis, by increasing the risk of bone metastasis 11-fold in NCCN bone scan indicated patients (Group 2). PMID- 26286636 TI - Toxicity of Nanoparticles and an Overview of Current Experimental Models. AB - Nanotechnology is a rapidly growing field having potential applications in many areas. Nanoparticles (NPs) have been studied for cell toxicity, immunotoxicity, and genotoxicity. Tetrazolium-based assays such as MTT, MTS, and WST-1 are used to determine cell viability. Cell inflammatory response induced by NPs is checked by measuring inflammatory biomarkers, such as IL-8, IL-6, and tumor necrosis factor, using ELISA. Lactate dehydrogenase (LDH) assay is used for cell membrane integrity. Different types of cell cultures, including cancer cell lines have been employed as in vitro toxicity models. It has been generally agreed that NPs interfere with either assay materials or with detection systems. So far, toxicity data generated by employing such models are conflicting and inconsistent. Therefore, on the basis of available experimental models, it may be difficult to judge and list some of the more valuable NPs as more toxic to biological systems and vice versa. Considering the potential applications of NPs in many fields and the growing apprehensions of FDA about the toxic potential of nanoproducts, it is the need of the hour to look for new internationally agreed free of bias toxicological models by focusing more on in vivo studies. PMID- 26286638 TI - Topologically inferring pathway activity toward precise cancer classification via integrating genomic and metabolomic data: prostate cancer as a case. AB - Precise cancer classification is a central challenge in clinical cancer research such as diagnosis, prognosis and metastasis prediction. Most existing cancer classification methods based on gene or metabolite biomarkers were limited to single genomics or metabolomics, and lacked integration and utilization of multiple 'omics' data. The accuracy and robustness of these methods when applied to independent cohorts of patients must be improved. In this study, we propose a directed random walk-based method to evaluate the topological importance of each gene in a reconstructed gene-metabolite graph by integrating information from matched gene expression profiles and metabolomic profiles. The joint use of gene and metabolite information contributes to accurate evaluation of the topological importance of genes and reproducible pathway activities. We constructed classifiers using reproducible pathway activities for precise cancer classification and risk metabolic pathway identification. We applied the proposed method to the classification of prostate cancer. Within-dataset experiments and cross-dataset experiments on three independent datasets demonstrated that the proposed method achieved a more accurate and robust overall performance compared to several existing classification methods. The resulting risk pathways and topologically important differential genes and metabolites provide biologically informative models for prostate cancer prognosis and therapeutic strategies development. PMID- 26286639 TI - Prospective association between body composition, physical activity and energy intake in young adults. AB - BACKGROUND/OBJECTIVES: Despite considerable research on the association between physical activity (PA) and body composition, there remains limited information on the directionality of the relationship. The present study examined the prospective associations among objectively measured PA, energy intake (EI) and body composition. SUBJECTS/METHODS: A convenience sample of 430 adults (49% male) between 21 and 35 years of age was followed over 1 year with repeated measurements taken every 3 months. BMI (kg/m(2)) and percent body fat (%BF) were calculated based on anthropometric measurements and dual energy X-ray absorptiometry. A multi-sensor device was worn over a period of 10 days to estimate total daily energy expenditure and time spent in different intensities. EI was calculated based on change in body composition and total daily energy expenditure. RESULTS: A total of 379 participants provided valid data. On average, participants experienced a significant weight gain of 1.2+/-4.3 kg during the 12-month observation period, which was associated with an increase in %BF (0.8+/-3.2 %). Average time spent in moderate-to-vigorous PA (MVPA) decreased significantly, whereas EI remained constant. Optimal linear mixed models, adjusting for age and sex, showed an inverse effect of MVPA on BMI and %BF, whereas EI only directly affected BMI (P<0.001). There was also a significant inverse effect of BMI and %BF on MVPA (P<0.001). CONCLUSIONS: Results of this study indicate an inverse reciprocal association between MVPA and measures of adiposity. Thus, primary preventive actions are warranted to avoid excess weight gain, which may result in a vicious cycle of weight gain and low PA. PMID- 26286640 TI - Atypical fractures of the femur: effect of anterolateral bowing of the femur on fracture location. AB - INTRODUCTION: Bisphosphonate therapy has been associated with the development of atypical femoral fractures. The most common sites of bisphosphonate-associated fractures are at the subtrochanteric region followed by the femoral shaft. This retrospective study hypothesizes that increasing anterolateral femoral bow is associated with more distal diaphyseal fractures. Awareness of this relationship is essential in the pre-operative planning and successful surgical management of these fractures. MATERIALS AND METHODS: We retrospectively reviewed twenty-one atypical subtrochanteric and femoral diaphyseal fractures and stress reactions within a 5-year period at our institution. Radiographs were assessed by two independent investigators for the degree of anterior and lateral femoral bow, and how distal the fracture was from the lesser trochanter. The relationship between the fracture position or stress reaction and degree of anterior and lateral bowing was analysed. RESULTS: There was a statistically significant linear relationship between anterior and lateral femoral bowing, and the fracture position along the diaphysis (correlation coefficient 0.63 (p = 0.002) and 0.684 (p = 0.001), respectively). Inter-observer reliability was highly correlated (Kappa value >0.8). CONCLUSION: In atypical femoral fractures associated with bisphosphonate use, more distal diaphyseal fractures occurred with a higher degree of anterior and lateral femoral bow. PMID- 26286641 TI - Meniscal tears associated with anterior cruciate ligament injury. AB - PURPOSE: To investigate the frequency of meniscal tear and the location of tear associated with anterior cruciate ligament (ACL) injury. SUBJECTS AND METHODS: We studied 549 patients (552 knees) who were diagnosed with ACL injury by arthroscopy at our center between January 2006 and March 2014 (8 years and 3 months). The subjects comprised 289 males and 263 females ranging in age from 13 to 66 (mean 26.1) years. The cause of injury was sports-related in 89.1 %, and the mean interval from injury to initial arthroscopy was 23 months. The patients were divided into two groups: arthroscopy performed within 8 weeks after injury (acute group; 256 knees) and more than 8 weeks after injury (chronic group; 296 knees). Frequency of meniscal tear and location of tear were compared between two groups. RESULTS: The incidence of meniscal tear diagnosed by arthroscopic examination was 79.2 % (437 of 552 knees) in all subjects; 72.7 % (186 of 256 knees) in acute group and 84.8 % (251 of 296 knees) in chronic group, and was significantly higher in chronic group. Regarding the locations of meniscal tears, in acute group (186 knees), medial meniscal tear only was found in 20 knees (10.8 %), lateral meniscal tear only in 129 knees (69.4 %), and bilateral (including medial and lateral) meniscal tears in 37 knees (19.9 %). In chronic group (251 knees), medial meniscal tear only was found in 62 knees (24.7 %), lateral meniscal tear only in 85 knees (33.9 %), and bilateral meniscal tears in 104 knees (41.4 %). Lateral meniscal tear was commonly associated with acute ACL injury, while medial meniscal tear with chronic ACL injury. Bucket handle tear was observed in 25 knees (medial: 17 knees, lateral: 8 knees) in acute group, and 81 knees (medial: 69 knees, lateral: 12 knees) in chronic group, and was more common in the chronic group. CONCLUSION: The incidence of meniscal tear associated with ACL injury is higher in chronic cases; the number of medial meniscal tears is particularly high, many of which require meniscectomy. Early ACL reconstruction is recommended also for the prevention of secondary meniscal tear. PMID- 26286642 TI - Precision imaging-its impact on image quality and diagnostic confidence in breast ultrasound examinations. AB - OBJECTIVE: To determine the effect of noise-reducing innovation-precision imaging (PI)-on image quality and diagnostic efficacy in breast ultrasound. METHODS: The study, which assessed four levels of PI from zero to three, consisted of two parts: image quality assessment and diagnostic efficacy evaluation. For the first part, 247 sets of ultrasound images displayed at each PI level were evaluated by 6 experienced breast imaging observers, by rating image quality using visual grading analysis on a 1-4 scale. For the diagnostic efficacy part 51 breast lesions were displayed at each PI level and scored 1-6 to generate a receiver operating characteristic (ROC) curve. These images were evaluated by radiologists and sonographers. Analyses were performed using non-parametric Friedman and Wilcoxon signed rank tests and a multireader multicase methodology. RESULTS: Statistically, higher scores of image quality were observed with increased levels of PI than with the zero setting (p < 0.001). The ROC analysis did not demonstrate any significant change in diagnostic efficacy, with mean scores for all observers being 0.79, 0.80, 0.81 and 0.81 for settings zero, one, two and three, respectively. CONCLUSION: This study suggested a perceived improvement in image quality with increasing levels of PI; however, no changes in diagnostic efficacy were noted. The importance of looking at the impact of new imaging technologies in a multifaceted way is emphasized. ADVANCES IN KNOWLEDGE: To our knowledge, this is the first article investigating the impact of the PI algorithm on ultrasound image quality and breast lesion characterization. PMID- 26286643 TI - Variants in RBP4 and AR genes modulate age at onset in familial amyloid polyneuropathy (FAP ATTRV30M). AB - Familial amyloid polyneuropathy (FAP) ATTRV30M is a neurodegenerative disorder due to point mutations in the transthyretin gene, with V30M being the commonest. FAP ATTRV30M shows a wide variation in age at onset (AO) between clusters, families and generations. Portuguese patients also show remarkable AO differences between genders. Genes found to be associated with FAP ATTRV30M pathways may act as AO modifiers. Our aim was to further explore the role of APCS and RBP4 genes and to study for the first time the involvement of sex-linked genetic modifiers - AR and HSD17B1 genes - in AO variation in Portuguese families. We collected DNA from a sample of 318 patients, currently under follow-up. A total of 18 tagging SNPs from APCS, RBP4, AR and HSD17B1 and 5 additional SNPs from APCS and RBP4 previously studied were genotyped. To account for nonindependency of AO between members of the same family, we used generalized estimating equations (GEEs). We found that APCS and RBP4 were associated with late AO. In addition, rs11187545 of the RBP4 was associated with an early AO. For the AR, in the male group three SNPs were associated with an early AO, whereas in the female group four were associated with both an early and later AO. These results strengthened the role of APCS and RBP4 genes and revealed for the first time the contribution of AR genes as an AO modifier in both males and females. These findings may have important implications in genetic counseling and for new therapeutic strategies. PMID- 26286644 TI - The more the merrier? How a few SNPs predict pigmentation phenotypes in the Northern German population. AB - Human pigmentation traits are of great interest to many research areas, from ancient DNA analysis to forensic science. We developed a gene-based predictive model for pigmentation phenotypes in a realistic target population for forensic case work from Northern Germany and compared our model with those brought forth by previous studies of genetically more heterogeneous populations. In doing so, we aimed at answering the following research questions: (1) do existing models allow good prediction of high-quality phenotypes in a genetically similar albeit more homogeneous population? (2) Would a model specifically set up for the more homogeneous population perform notably better than existing models? (3) Can the number of markers included in existing models be reduced without compromising their predictive capability in the more homogenous population? We investigated the association between eye, hair and skin colour and 12 candidate single nucleotide polymorphisms (SNPs) from six genes. Our study comprised two samples of 300 and 100 individuals from Northern Germany. SNP rs12913832 in HERC2 was found to be strongly associated with blue eye colour (odds ratio=40.0, P<1.2 * 10(-4)) and to yield moderate predictive power (AUC: 77%; sensitivity: 90%, specificity: 63%, both at a 0.5 threshold for blue eye colour probability). SNP associations with hair and skin colour were weaker and genotypes less predictive. A comparison with two recently published sets of markers to predict eye and hair colour revealed that the consideration of additional SNPs with weak-to-moderate effect increased the predictive power for eye colour, but not for hair colour. PMID- 26286645 TI - Transitioning From Community-Based to Institutional Long-term Care: Comparing 1915(c) Waiver and PACE Enrollees. AB - Purpose of the Study: To compare the risk of long-term nursing home (NH) admission and the level of functional and cognitive impairment at the time of long-term NH admission in the Program of All-Inclusive Care for the Elderly (PACE) and in 1915(c) aged and aged and disabled waiver programs. Design and Methods: Cohorts of new waiver and PACE enrollees in 12 states were identified (in 2005-2007) and followed (through 2009) using the Medicaid Analytic Extract and the Minimum Data Set. Individual-level outcomes of interest were time from waiver or PACE enrollment to long-term (90+ days) NH admission and functional (29 point activities of daily living [ADL]) and cognitive (7-point Cognitive Performance Scale [CPS]) impairment at NH admission. An overall measure of impairment was also created and categorized as low (ADL < 17 and CPS < 3) versus high (ADL >= 17 or CPS >= 3). The key independent variable was enrollment in PACE versus waiver program. County-level covariates were included. Analyses employed multivariable models including competing risk proportional hazard and linear and logistic regressions. Results: Compared with waiver enrollees, PACE enrollees had 31% lower risk of long-term NH admission (p < .001). At NH admission, they were overall significantly (p < .0001) more cognitively impaired (0.34 point), with 55% higher odds of severe (CPS >= 4) cognitive impairment (p < .001) and 45% higher odds of having overall high impairment (p = .003). Implications: PACE may be more effective than 1915(c) aged and aged and disabled waiver programs in reducing long-term NH use and may be particularly well suited to supporting cognitively impaired individuals, enabling them to remain in the community longer. PMID- 26286646 TI - Sequence of Functional Loss and Recovery in Nursing Homes. AB - PURPOSE OF THE STUDY: This study provides benchmarks for likelihood, number of days until, and sequence of functional decline and recovery. DESIGN AND METHODS: We analyzed activities of daily living (ADLs) of 296,051 residents in Veteran Affairs nursing homes between January 1, 2000 and October 9, 2012. ADLs were extracted from standard minimum data set assessments. Because of significant overlap between short- and long-stay residents, we did not distinguish between these populations. Twenty-five combinations of ADL deficits described the experience of 84.3% of all residents. A network model described transitions among these 25 combinations. The network was used to calculate the shortest, longest, and maximum likelihood paths using backward induction methodology. Longitudinal data were used to derive a Bayesian network that preserved the sequence of occurrence of 9 ADL deficits. RESULTS: The majority of residents (57%) followed 4 pathways in loss of function. The most likely sequence, in order of occurrence, was bathing, grooming, walking, dressing, toileting, bowel continence, urinary continence, transferring, and feeding. The other three paths occurred with reversals in the order of dressing/toileting and bowel/urinary continence. ADL impairments persisted without any change for an average of 164 days (SD = 62). Residents recovered partially or completely from a single impairment in 57% of cases over an average of 119 days (SD = 41). Recovery rates declined as residents developed more than 4 impairments. IMPLICATIONS: Recovery of deficits among those studied followed a relatively predictable path, and although more than half recovered from a single functional deficit, recovery exceeded 100 days suggesting time to recover often occurs over many months. PMID- 26286647 TI - Female heterogamety in Madagascar chameleons (Squamata: Chamaeleonidae: Furcifer): differentiation of sex and neo-sex chromosomes. AB - Amniotes possess variability in sex determining mechanisms, however, this diversity is still only partially known throughout the clade and sex determining systems still remain unknown even in such a popular and distinctive lineage as chameleons (Squamata: Acrodonta: Chamaeleonidae). Here, we present evidence for female heterogamety in this group. The Malagasy giant chameleon (Furcifer oustaleti) (chromosome number 2n = 22) possesses heteromorphic Z and W sex chromosomes with heterochromatic W. The panther chameleon (Furcifer pardalis) (2n = 22 in males, 21 in females), the second most popular chameleon species in the world pet trade, exhibits a rather rare Z1Z1Z2Z2/Z1Z2W system of multiple sex chromosomes, which most likely evolved from W-autosome fusion. Notably, its neo-W chromosome is partially heterochromatic and its female-specific genetic content has expanded into the previously autosomal region. Showing clear evidence for genotypic sex determination in the panther chameleon, we resolve the long standing question of whether or not environmental sex determination exists in this species. Together with recent findings in other reptile lineages, our work demonstrates that female heterogamety is widespread among amniotes, adding another important piece to the mosaic of knowledge on sex determination in amniotes needed to understand the evolution of this important trait. PMID- 26286648 TI - Precancerous Lesions and Carcinoma of the Pancreas. PMID- 26286650 TI - MicroRNAs and Noncoding RNAs in Hepatic Lipid and Lipoprotein Metabolism: Potential Therapeutic Targets of Metabolic Disorders. AB - Noncoding RNAs and microRNAs (miRNAs) represent an important class of regulatory molecules that modulate gene expression. The role of miRNAs in diverse cellular processes such as cancer, apoptosis, cell differentiation, cardiac remodeling, and inflammation has been intensively explored. Recent studies further demonstrated the important roles of miRNAs and noncoding RNAs in modulating a broad spectrum of genes involved in lipid synthesis and metabolic pathways. This overview focuses on the role of miRNAs in hepatic lipid and lipoprotein metabolism and their potential as therapeutic targets for metabolic syndrome. This includes recent advances made in the understanding of their target pathways and the clinical development of miRNAs in lipid metabolic disorders. PMID- 26286651 TI - Stress effects on the hippocampus: a critical review. AB - Uncontrollable stress has been recognized to influence the hippocampus at various levels of analysis. Behaviorally, human and animal studies have found that stress generally impairs various hippocampal-dependent memory tasks. Neurally, animal studies have revealed that stress alters ensuing synaptic plasticity and firing properties of hippocampal neurons. Structurally, human and animal studies have shown that stress changes neuronal morphology, suppresses neuronal proliferation, and reduces hippocampal volume. Since the inception of stress research nearly 80 years ago, much focus has been on the varying levels of hypothalamic-pituitary adrenal (HPA) axis neuroendocrine hormones, namely glucocorticoids, as mediators of the myriad stress effects on the hippocampus and as contributing factors to stress-associated psychopathologies such as post-traumatic stress disorder (PTSD). However, reports of glucocorticoid-produced alterations in hippocampal functioning vary widely across studies. This review provides a brief history of stress research, examines how the glucocorticoid hypothesis emerged and guides contemporary stress research, and considers alternative approaches to understanding the mechanisms underlying stress effects on hippocampal functioning. PMID- 26286652 TI - Neurobehavioral perspectives on the distinction between fear and anxiety. AB - In this review, we discuss the usefulness of the distinction between fear and anxiety. The clinical use of the labels is ambiguous, often defining one in terms of the other. We first consider what a useful, objective, and scientifically valid definition would entail and then evaluate several fear/anxiety distinctions that have been made in the neurobiological literature. A strong distinction should specify the difference in conditions that lead to fear versus anxiety. Additionally, fear and anxiety should generate distinct sets of behaviors. Ideally, the two states should be supported by distinguishable neuroanatomical circuits. Such a conceptualization would be consistent with the National Institute of Mental Health's Research Domain Criteria (RDoc). The majority of neurobiological approaches to the fear versus anxiety distinction fail to differentiate the two states in terms of behavior, often using the exact same behavioral measures as indicators. Of the two that do, only Predatory Imminence Theory provides a distinction both in terms of cause and effect. Indeed, that approach provides a ready distinction of anxiety, fear, and panic in terms of both antecedent conditions and response selection rules. Additionally, it appeals to distinct neural circuits to generate these modes of action. PMID- 26286654 TI - Entorhinal-hippocampal neuronal circuits bridge temporally discontiguous events. AB - The entorhinal cortex (EC)-hippocampal (HPC) network plays an essential role for episodic memory, which preserves spatial and temporal information about the occurrence of past events. Although there has been significant progress toward understanding the neural circuits underlying the spatial dimension of episodic memory, the relevant circuits subserving the temporal dimension are just beginning to be understood. In this review, we examine the evidence concerning the role of the EC in associating events separated by time--or temporal associative learning--with emphasis on the function of persistent activity in the medial entorhinal cortex layer III (MECIII) and their direct inputs into the CA1 region of HPC. We also discuss the unique role of Island cells in the medial entorhinal cortex layer II (MECII), which is a newly discovered direct feedforward inhibitory circuit to CA1. Finally, we relate the function of these entorhinal cortical circuits to recent findings concerning hippocampal time cells, which may collectively activate in sequence to bridge temporal gaps between discontiguous events in an episode. PMID- 26286653 TI - Synchrony and desynchrony in circadian clocks: impacts on learning and memory. AB - Circadian clocks evolved under conditions of environmental variation, primarily alternating light dark cycles, to enable organisms to anticipate daily environmental events and coordinate metabolic, physiological, and behavioral activities. However, modern lifestyle and advances in technology have increased the percentage of individuals working in phases misaligned with natural circadian activity rhythms. Endogenous circadian oscillators modulate alertness, the acquisition of learning, memory formation, and the recall of memory with examples of circadian modulation of memory observed across phyla from invertebrates to humans. Cognitive performance and memory are significantly diminished when occurring out of phase with natural circadian rhythms. Disruptions in circadian regulation can lead to impairment in the formation of memories and manifestation of other cognitive deficits. This review explores the types of interactions through which the circadian clock modulates cognition, highlights recent progress in identifying mechanistic interactions between the circadian system and the processes involved in memory formation, and outlines methods used to remediate circadian perturbations and reinforce circadian adaptation. PMID- 26286655 TI - Reward processing by the dorsal raphe nucleus: 5-HT and beyond. AB - The dorsal raphe nucleus (DRN) represents one of the most sensitive reward sites in the brain. However, the exact relationship between DRN neuronal activity and reward signaling has been elusive. In this review, we will summarize anatomical, pharmacological, optogenetics, and electrophysiological studies on the functions and circuit mechanisms of DRN neurons in reward processing. The DRN is commonly associated with serotonin (5-hydroxytryptamine; 5-HT), but this nucleus also contains neurons of the neurotransmitter phenotypes of glutamate, GABA and dopamine. Pharmacological studies indicate that 5-HT might be involved in modulating reward- or punishment-related behaviors. Recent optogenetic stimulations demonstrate that transient activation of DRN neurons produces strong reinforcement signals that are carried out primarily by glutamate. Moreover, activation of DRN 5-HT neurons enhances reward waiting. Electrophysiological recordings reveal that the activity of DRN neurons exhibits diverse behavioral correlates in reward-related tasks. Studies so far thus demonstrate the strong power of DRN neurons in reward signaling and at the same time invite additional efforts to dissect the roles and mechanisms of different DRN neuron types in various processes of reward-related behaviors. PMID- 26286659 TI - Sodium Selenite Decreased HDAC Activity, Cell Proliferation and Induced Apoptosis in Three Human Glioblastoma Cells. AB - AIMS: Selenium (Se) is an essential trace element for human health which also has antitumor properties. Little is known about its effects on brain tumor cells (BTC). The aim of this study was to investigate the anticancer effects of sodium selenite (SS) including histone deacetylase (HDAC) activity in three human glioblastoma (GBM) cell lines (LN229, T98G and U87). MATERIALS & METHODS: LN229, T98G and U87 GBM cell lines were treated with variable doses of SS for time varying from 24 to 72h. HDAC activity, cell proliferation, toxicity, cell death process, caspase-3 and MMP2 activities and Se absorption were evaluated. RESULTS: SS modulated all the parameters tested in a dose- and time-dependent manner. We found that SS decreased HDAC activity, blocked cell proliferation and cell cycle at the G2 phase, triggered an apoptotic cell death process caspase-3-dependent and reduced MMP2 activities. All these effects were performed whereas SS was weakly absorbed (<2%). CONCLUSIONS: SS decreasing HDAC activity exhibited interesting antitumor properties in GBM cells which may be taken into account in the novel strategies for achieving tumor growth inhibition and cytotoxicity. Epigenetic modifications induced by SS should be evaluated in further studies. PMID- 26286658 TI - The need for novel informatics tools for integrating and planning research in molecular and cellular cognition. AB - The sheer volume and complexity of publications in the biological sciences are straining traditional approaches to research planning. Nowhere is this problem more serious than in molecular and cellular cognition, since in this neuroscience field, researchers routinely use approaches and information from a variety of areas in neuroscience and other biology fields. Additionally, the multilevel integration process characteristic of this field involves the establishment of experimental connections between molecular, electrophysiological, behavioral, and even cognitive data. This multidisciplinary integration process requires strategies and approaches that originate in several different fields, which greatly increases the complexity and demands of this process. Although causal assertions, where phenomenon A is thought to contribute or relate to B, are at the center of this integration process and key to research in biology, there are currently no tools to help scientists keep track of the increasingly more complex network of causal connections they use when making research decisions. Here, we propose the development of semiautomated graphical and interactive tools to help neuroscientists and other biologists, including those working in molecular and cellular cognition, to track, map, and weight causal evidence in research papers. There is a great need for a concerted effort by biologists, computer scientists, and funding institutions to develop maps of causal information that would aid in integration of research findings and in experiment planning. PMID- 26286656 TI - beta-Adrenergic receptor signaling and modulation of long-term potentiation in the mammalian hippocampus. AB - Encoding new information in the brain requires changes in synaptic strength. Neuromodulatory transmitters can facilitate synaptic plasticity by modifying the actions and expression of specific signaling cascades, transmitter receptors and their associated signaling complexes, genes, and effector proteins. One critical neuromodulator in the mammalian brain is norepinephrine (NE), which regulates multiple brain functions such as attention, perception, arousal, sleep, learning, and memory. The mammalian hippocampus receives noradrenergic innervation and hippocampal neurons express beta-adrenergic receptors, which are known to play important roles in gating the induction of long-lasting forms of synaptic potentiation. These forms of long-term potentiation (LTP) are believed to importantly contribute to long-term storage of spatial and contextual memories in the brain. In this review, we highlight the contributions of noradrenergic signaling in general and beta-adrenergic receptors in particular, toward modulating hippocampal LTP. We focus on the roles of NE and beta-adrenergic receptors in altering the efficacies of specific signaling molecules such as NMDA and AMPA receptors, protein phosphatases, and translation initiation factors. Also, the roles of beta-adrenergic receptors in regulating synaptic "tagging" and "capture" of LTP within synaptic networks of the hippocampus are reviewed. Understanding the molecular and cellular bases of noradrenergic signaling will enrich our grasp of how the brain makes new, enduring memories, and may shed light on credible strategies for improving mental health through treatment of specific disorders linked to perturbed memory processing and dysfunctional noradrenergic synaptic transmission. PMID- 26286660 TI - Full circle: Resolving an adolescent's end-of-life issues. AB - We report the challenges in managing a troubled, medically ill adolescent with end-of-life issues. Our role as multi-professional service providers complemented the family's efforts to help him reconcile with himself before death. The present experience enhances understanding of the biopsychosocial aspects of care. Every child has the right to optimal care. PMID- 26286661 TI - Exudativory in the Asian loris, Nycticebus: Evolutionary divergence in the toothcomb and M3. AB - OBJECTIVES: Slow lorises (Nycticebus spp.) are obligate exudativores that gouge tree bark. Dental adaptations for gouging within marmosets, the only other known primate obligate exudativore, are well-known but dental adaptations in Nycticebus are largely unidentified. In an effort to more completely understand potential dental adaptions within Nycticebus and the evolution of this dietary niche within Primates as an order, the present study examined dental morphometrics in the Asian lorises (Nycticebus and Loris). MATERIALS AND METHODS: We compared dental morphometrics between Nycticebus and the insectivorous slender lorises (Loris). Measurements from the toothcomb and select other teeth were taken from 92 specimens. Each variable was scaled by the geometric mean and resulting mean ratios were statistically compared between groups. A biomechanical shape variable was also calculated to estimate the ability of the toothcomb to resist bending that may be experienced during gouging. RESULTS: Toothcombs in Nycticebus were significantly (P < 0.05) more narrow, shorter, and thicker than those in Loris and had a higher calculated ability to withstand bending forces. Nycticebus also had reduced size in the last lower molar relative to Loris. CONCLUSIONS: The more robust, "squared off" toothcomb in Nycticebus matches behavioral observations that these primates gouge to access exudates. Results of the present study indicate that the toothcomb is the likely candidate for the dental tool used in gouging. The size reduction of the lower last molar in Nycticebus, a trait also found in a previous study in exudativorous galagos, may indicate that there is reduced selective pressure in a diet where little mastication would be needed to mechanically process exudates. These results may indicate that reduction in molar size could be a potential dental signature for exudativory, but further studies on a wider phylogenetic range of exudativorous primates would be necessary. PMID- 26286662 TI - Effects of botulinum toxin A and/or bimanual task-oriented therapy on upper extremity activities in unilateral Cerebral Palsy: a clinical trial. AB - BACKGROUND: This study reports on the effects of botulinum toxin A (BoNT-A) injections in the upper extremity (UE) in children with unilateral Cerebral Palsy (uCP) combined with bimanual task-oriented therapy (BITT) or either treatment modality performed separately. Bimanual activities were measured with the Assisting Hand Assessment (AHA), the ABILHand-Kids questionnaire (AK), the Observational Skills Assessment Score (OSAS). Goal achievement was measured with Goal Attainment Scaling (GAS), using blind video assessment, and the Canadian Occupational Performance Measure (COPM). METHODS: Thirty-five children, mean age 7.14 years (SD 2.63), 11 Manual Ability Classification Score (MACS) I, 15 MACS II and 9 MACS III, participated. The trial started with four study groups: BoNT-A only (n = 5), BITT-only (n = 11), BoNT-A + BITT (n = 13), and control (n = 6). Twenty-two children were randomised, 13 children received their parents' preferred treatment: BoNT-A + BITT or BITT-only. Three comparisons were analysed: BITT (BoNT-A + BITT and BITT-only; n = 24) versus no BITT (BoNT-A-only and control; n = 11), BoNT-A (BoNT-A-only and BoNT-A + BITT; n = 18) versus no BoNT-A (BITT-only and control; n = 17), and the additional effect of BoNT-A (BoNT-A + BITT versus BITT-only). Follow-up time: 24 weeks. RESULTS: No significant differences between the groups were found on the AHA. The amount of use of both hands on the OSAS was significantly better in the BoNT-A group in the beading and sandwich-making task. The BoNT-A group also showed significant improvement in the quality scores of the OSAS: the wrist position during grasping and holding, especially in the younger children. The BITT group improved significantly on the AK and significantly more on the performance and satisfaction scores of the COPM at 12 and 24 weeks regarding several goals. BoNT-A showed a significant negative effect at 12 and 24 weeks in the most important goal. BITT, more than BoNT-A + BITT, showed positive effects on the GAS score at 12 (significant), 18 and 24 weeks. CONCLUSIONS: BoNT-A has a positive effect on quality of movement and amount of use of the affected UE during the 3 months' working time. BoNT-A has no additional effect on bimanual performance and goal achievement. BITT has a positive effect on goal achievement and bimanual performance, even up to 6 weeks after therapy had stopped. TRIAL REGISTRATION: Current Controlled Trials ISRCTN69541857. PMID- 26286663 TI - Recent Developments on 1,2,4-Triazole Nucleus in Anticancer Compounds: A Review. AB - 1,2,4-triazole is an important nucleus present in a large number of compounds. More than thirty-five compounds containing this nucleus are introduced into the market. 1,2,4-triazole nucleus is stable to metabolism and acts as an important pharmacophore by interacting at the active site of a receptor as hydrogen bond acceptor and as a donor. Due to its polar nature, the triazole nucleus can increase the solubility of the ligand and it can significantly improve the pharmacological profile of the drug. A large number of 1,2,4-triazole derivatives are reported to possess a wide range of bioactivities including anti-cancer activity. This review article describes the role of 1,2,4-triazole nucleus in different types of anti-cancer agents such as nucleoside based anti-cancer agents, kinase inhibitors, tubulin modulators, aromatase and steroid sulfatase inhibitors, methionine aminopeptidase inhibitors, tankyrase inhibitors and metal complex based anti-cancer agents. It is expected that the current review article will provide insight into various ligand-receptor interactions and help in the rational design and development of novel 1,2,4-triazole based anti-cancer drugs with improved selectivity for cancer cells. PMID- 26286664 TI - Investigating the psychometric properties of the Geriatric Suicide Ideation Scale (GSIS) among community-residing older adults. AB - OBJECTIVES: To investigate the psychometric properties of the Geriatric Suicide Ideation Scale (GSIS) among community-residing older adults. METHOD: We recruited 173 voluntary participants, 65 years and older, into a 2+ year longitudinal study of the onset or exacerbation of depressive symptoms and suicide ideation. We assessed the internal consistency of the GSIS and its four component subscales, and its shorter and longer duration test-retest reliability, convergent (depression, social hopelessness, and loneliness), divergent (psychological well being, life satisfaction, perceived social support, and self-rated health), discriminant (basic and instrumental activities of daily living and social desirability), criterion (history of suicide behavior), and predictive validity (future suicide ideation). RESULTS: The GSIS demonstrated strong test-retest reliability and internal consistency. Baseline GSIS scores were significantly positively associated with suicide risk factors, negatively associated with potential resiliency factors, and not associated with functional impairment or social desirability. GSIS scores significantly differentiated between participants with as compared to those without a history of suicide behavior. Baseline GSIS scores significantly predicted suicide ideation at a 2+ year follow up assessment. CONCLUSION: Findings suggest strong measurement characteristics for the GSIS with community-residing older adults, including impressive consistency over time. These results are consistent with research attesting to the empirical and pragmatic strengths of this measure. These findings have implications for the monitoring of suicide risk when aiming to enhance mental health and well-being and prevent suicide in later life. PMID- 26286657 TI - Sex steroid hormones matter for learning and memory: estrogenic regulation of hippocampal function in male and female rodents. AB - Ample evidence has demonstrated that sex steroid hormones, such as the potent estrogen 17beta-estradiol (E2), affect hippocampal morphology, plasticity, and memory in male and female rodents. Yet relatively few investigators who work with male subjects consider the effects of these hormones on learning and memory. This review describes the effects of E2 on hippocampal spinogenesis, neurogenesis, physiology, and memory, with particular attention paid to the effects of E2 in male rodents. The estrogen receptors, cell-signaling pathways, and epigenetic processes necessary for E2 to enhance memory in female rodents are also discussed in detail. Finally, practical considerations for working with female rodents are described for those investigators thinking of adding females to their experimental designs. PMID- 26286665 TI - Life-history plasticity in female threespine stickleback. AB - The postglacial adaptive radiation of the threespine stickleback fish (Gasterosteus aculeatus) has been widely used to investigate the roles of both adaptive evolution and plasticity in behavioral and morphological divergence from the ancestral condition represented by present-day oceanic stickleback. These phenotypes tend to exhibit high levels of ecotypic differentiation. Population divergence in life history has also been well studied, but in contrast to behavior and morphology, the extent and importance of plasticity has been much less well studied. In this review, we summarize what is known about life-history plasticity in female threespine stickleback, considering four traits intimately associated with reproductive output: age/size at maturation, level of reproductive effort, egg size and clutch size. We envision life-history plasticity in an iterative, ontogenetic framework, in which females may express plasticity repeatedly across each of several time frames. We contrast the results of laboratory and field studies because, for most traits, these approaches give somewhat different answers. We provide ideas on what the cues might be for observed plasticity in each trait and, when possible, we inquire about the relative costs and benefits to expressed plasticity. We end with an example of how we think plasticity may play out in stickleback life history given what we know of plasticity in the ancestor. PMID- 26286666 TI - Polygamy and an absence of fine-scale structure in Dendroctonus ponderosae (Hopk.) (Coleoptera: Curcilionidae) confirmed using molecular markers. AB - An understanding of mating systems and fine-scale spatial genetic structure is required to effectively manage forest pest species such as Dendroctonus ponderosae (mountain pine beetle). Here we used genome-wide single-nucleotide polymorphisms to assess the fine-scale genetic structure and mating system of D. ponderosae collected from a single stand in Alberta, Canada. Fine-scale spatial genetic structure was absent within the stand and the majority of genetic variation was best explained at the individual level. Relatedness estimates support previous reports of pre-emergence mating. Parentage assignment tests indicate that a polygamous mating system better explains the relationships among individuals within a gallery than the previously reported female monogamous/male polygynous system. Furthermore, there is some evidence to suggest that females may exploit the galleries of other females, at least under epidemic conditions. Our results suggest that current management models are likely to be effective across large geographic areas based on the absence of fine-scale genetic structure. PMID- 26286668 TI - The Clinical and Socio-Economic Relevance of Increased IPMN Detection Rates and Management Choices. AB - BACKGROUND: Increased usage of computed tomography and magnetic resonance imaging has led to a large increase in identified pancreatic cysts of up to 25% in population-based studies. The clinical and economic relevance of identifying so many cystic lesions has not been established. Compared to other organs such as liver or kidney, dysontogenetic pancreatic cysts are rare. Pancreatic cysts comprise a variety of benign, premalignant or malignant lesions; however, precise diagnosis before resection has an accuracy of only 80%. The focus of recent research was the malignant potential of intraductal papillary mucinous neoplasms (IPMN) with the aim of establishing clinical pathways addressing risk of malignancy, age and comorbidity, treatment-related morbidity and mortality as well as cost-effectiveness of treatment and surveillance. The focus of this review is to analyze the clinical and socio-economic relevance as well as the cost-benefit relation for IPMNs. METHODS: For analysis, the following MESH terms were used to identify original articles, reviews, and guidelines in PubMed: ('intraductal papillary mucinous neoplasm' OR 'pancreatic cysts') and (incidence OR relevance OR socio-economic OR economic OR cost-effectiveness OR cost benefit). The retrieved publications were reviewed with a focus on clinical and socio-economic relevance in relation to the increasing incidence of IPMN. RESULTS: Addressing the increasing prevalence of pancreatic cystic lesions, recent consensus guidelines suggested criteria for risk stratification according to 'worrisome features' and 'high-risk stigmata'. Recent prospective cohort studies evaluated whether these can be applied in clinical practice. Evaluation of three different clinical scenarios with regard to costs and quality-adjusted life years suggested a better effectiveness of surveillance after initial risk stratification by endoscopic ultrasound-guided fine-needle aspiration with cyst fluid analysis compared with immediate resection or follow-up without further intervention. Of interest, the 'immediate surgery' strategy was lowest for cost effectiveness. CONCLUSIONS: The increasing incidence of identified pancreatic cysts requires an improved strategy for non-invasive risk stratification based on advanced imaging strategies. In light of a malignancy risk of 2% for branch-duct IPMN, the socio-economic necessity of a balance between surveillance and resection has to be agreed on. PMID- 26286669 TI - Validated MicroRNA Target Databases: An Evaluation. AB - Preclinical Research Positive findings from preclinical and clinical studies involving depletion or supplementation of microRNA (miRNA) engender optimism about miRNA-based therapeutics. However, off-target effects must be considered. Predicting these effects is complicated. Each miRNA may target many gene transcripts, and the rules governing imperfectly complementary miRNA: target interactions are incompletely understood. Several databases provide lists of the relatively small number of experimentally confirmed miRNA: target pairs. Although incomplete, this information might allow assessment of at least some of the off target effects. We evaluated the performance of four databases of experimentally validated miRNA: target interactions (miRWalk 2.0, miRTarBase, miRecords, and TarBase 7.0) using a list of 50 alphabetically consecutive genes. We examined the provided citations to determine the degree to which each interaction was experimentally supported. To assess stability, we tested at the beginning and end of a five-month period. Results varied widely by database. Two of the databases changed significantly over the course of 5 months. Most reported evidence for miRNA: target interactions were indirect or otherwise weak, and relatively few interactions were supported by more than one publication. Some returned results appear to arise from simplistic text searches that offer no insight into the relationship of the search terms, may not even include the reported gene or miRNA, and may thus, be invalid. We conclude that validation databases provide important information, but not all information in all extant databases is up-to date or accurate. Nevertheless, the more comprehensive validation databases may provide useful starting points for investigation of off-target effects of proposed small RNA therapies. PMID- 26286670 TI - The potential impact of NIPT as a second-tier screen on the outcomes of high-risk pregnancies with rare chromosomal abnormalities. AB - AIM: To describe the potential impact of using noninvasive prenatal testing (NIPT) as a second-tier test, on the diagnosis and outcomes of pregnancies identified as high risk through first trimester screening (FTS) in a cohort of real pregnancies. MATERIALS AND METHODS: Western Australian FTS and diagnostic data (2007-2009) were linked to pregnancy outcomes. Karyotype results from invasive prenatal testing in high-risk women were analysed. The outcomes of abnormal results that would not be detected by NIPT, assuming a panel of trisomy 21/18/13 and sex chromosome aneuploidies, and the likelihood of diagnosis in a screening model using NIPT as a second-tier test are described. RESULTS: Abnormal karyotype results were reported in 224 of 1488 (15%) women with high-risk pregnancies having invasive diagnostic testing. NIPT potentially would have identified 85%. The 33 abnormalities unidentifiable by NIPT were triploidies (n = 7, 21%), balanced (n = 8, 24%) and unbalanced rearrangements (n = 10, 30%) and level III mosaicisms (n = 8, 24%). For conditions not identifiable by NIPT, fetal sonographic appearance was likely to have led to invasive testing for 10 of 17 (59%) pathogenic abnormalities. If a policy was adopted recommending invasive testing for FTS risk >1:50 and/or ultrasound detected abnormality, the residual risk of an unidentified pathogenic chromosomal abnormality in those without a diagnosis would have been 0.33% (95% CI 0.01-0.65%). CONCLUSIONS: A screening model with NIPT as a second-tier for high-risk pregnancies would be unlikely to have changed the outcome for the majority of pregnancies. Optimising the diagnosis of rare pathogenic abnormalities requires clear indicators for invasive testing over NIPT. PMID- 26286671 TI - Ischaemic stroke patients who present early but with therapeutic anticoagulation: a treatment dilemma. PMID- 26286672 TI - Characterization of the diversity of mycosporine-like amino acids in lichens from high altitude region of Himalaya. AB - Lichens are tolerant to a number of environmental variables including high intensity solar radiations, which is mainly due to the presence of chemical substances in the thallus. Especially, cyanobacterial lichens synthesize a unique class of chemical substances known as mycosporine-like amino acids (MAAs) the primary characteristic of which is strong ultraviolet (UV) absorption between 300 and 360 nm. In view of its UV-protecting potential, the applicability of mass spectral fragmentation using electrospray ionization tandem mass spectrometric analysis for the characterization of MAAs in lichen samples was explored. MAA compounds were characterized in four cyanobacteria-containing lichen species belonging to genus Peltigera, Stereocaulon and Lobaria. Among them, Peltigera and Lobaria are true cyanobacteria containing lichens (cyanolichens) while Stereocaulon is a tripartite lichen, as it contains both green algae (in the thallus) and cyanobacteria (in the cephalodia), collected from higher altitudes of Himalaya (Tungnath-Chopta in Garhwal Himalaya, 3432 m) from an exposed locality experiencing high light intensity. Mass spectral data of distinctive fragmentation pattern revealed that all the four species have good diversity of MAA compounds, especially Lobaria retigera was found to be enriched with highest diversity of oxo and imino MAAs. Overall, different numbers of oxo and imino MAA compounds were detected in the remaining lichen species. Good diversity of imino MAAs has ecological significance which is required to be investigated further. Moreover, the impressive diversity characterized in each lichen species suggests that lichens should be thoroughly studied for their MAAs contents. PMID- 26286673 TI - Novel Boronlectins Based on Bispyridium Salt with a Flexible Linker: Discriminative Sensing of Lactose and Other Monosaccharides and Disaccharides in Aqueous Solution. AB - N,N-Di-2-picolylamine (DPA)-derived diboronic acid receptors (NHBAs) with a flexible linker were designed and synthesized in this study, and two-component sensing ensembles based on cationic NHBAs and an anionic fluorescent indicator 8 hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS) were successfully developed for both monosaccharides and disaccharides sensing. The dibranched ortho-substituted receptor NHoBA exhibited unexpected selectivity towards lactose among five disaccharides used. The discrimination of five disaccharides and six monosaccharides was finally achieved by the integrated sensor array through linear discriminant analysis (LDA). PMID- 26286667 TI - Interglacial refugia preserved high genetic diversity of the Chinese mole shrew in the mountains of southwest China. AB - The mountains of southwest China (MSC) harbor extremely high species diversity; however, the mechanism behind this diversity is unknown. We investigated to what degree the topography and climate change shaped the genetic diversity and diversification in these mountains, and we also sought to identify the locations of microrefugia areas in these mountains. For these purposes, we sampled extensively to estimate the intraspecific phylogenetic pattern of the Chinese mole shrew (Anourosorex squamipes) in southwest China throughout its range of distribution. Two mitochondrial genes, namely, cytochrome b (CYT B) and NADH dehydrogenase subunit 2 (ND2), from 383 archived specimens from 43 localities were determined for phylogeographic and demographic analyses. We used the continuous-diffusion phylogeographic model, extensive Bayesian skyline plot species distribution modeling (SDM) and approximate Bayesian computation (ABC) to explore the changes in population size and distribution through time of the species. Two phylogenetic clades were identified, and significantly higher genetic diversity was preserved in the southern subregion of the mountains. The results of the SDM, continuous-diffusion phylogeographic model, extensive Bayesian skyline plot and ABC analyses were congruent and supported that the Last Interglacial Maximum (LIG) was an unfavorable period for the mole shrews because of a high degree of seasonality; A. squamipes survived in isolated interglacial refugia mainly located in the southern subregion during the LIG and rapidly expanded during the last glacial period. These results furnished the first evidence for major Pleistocene interglacial refugia and a latitudinal effect in southwest China, and the results shedding light on the higher level of species richness in the southern subregion. PMID- 26286674 TI - Development of an indirect enzyme-linked immunosorbent assay test for detecting antibodies to chicken astrovirus in chicken sera. AB - The development of an indirect enzyme-linked immunosorbent assay (ELISA) for the serological diagnosis of Group B chicken astrovirus (CAstV) infections is described. The test was based on the use of an affinity-purified capsid antigen, specific to CAstV isolate 11672, produced as a glutathione-S-transferase N terminal fusion protein by a recombinant baculovirus. Strongly positive ELISA signals were elicited against experimentally produced antisera raised to CAstVs from Group B (subgroups i and ii) but were negative for antisera raised to a Group A CAstV. Using a panel of 240 selected serum samples, 99% agreement was observed when the results obtained by ELISA were compared to those from an indirect immunofluorescence test for CAstV 11672. The ELISA test was applied to 68 serum sets comprising 1864 samples, which were obtained from parent and grandparent flocks originating mainly in the UK. Of the 52 sets containing ELISA positive samples, 24 sets had >75% samples positive and nine sets had <25% samples positive and were regarded as having high and low seropositivities, respectively. Of the 1864 serum samples tested 1090 (58.5%) were ELISA positive and of these, 234 sera (21.5%) produced strongly positive signals, whereas moderately positive and weakly positive signals were produced by 562 (51.5%) and 294 (27%) sera. When used for flock screening purposes, this ELISA test can be used to (i) investigate the occurrence of first-time CAstV infections of parent flocks during lay and the possible adverse effects caused by vertically transmitted CAstV infections on broiler hatchability and performance and (ii) diagnose Group B CAstV infections within specific pathogen free flocks. PMID- 26286675 TI - Classifying ADRs--does dose matter? PMID- 26286676 TI - High Sensitivity RT-qPCR Assay of Nonlabeled siRNA in Small Blood Volume for Pharmacokinetic Studies: Application to Survivin siRNA. AB - RNAi therapeutics provide an opportunity to correct faulty genes, and several RNAi have entered clinical evaluation. The existing quantification methods typically use radioactivity- or fluorescence-labeled RNAi, require large blood volumes, and/or have a limited dynamic detection range. We established a quantitative reverse transcriptase real-time polymerase chain reaction (RT-qPCR) assay to measure RNAi; the model analyte was survivin siRNA (siSurvivin). A second siRNA was used as the internal standard. The three major steps were (a) extraction of the two siRNAs from blood or water, (b) synthesis of their cDNA by poly-A extension, and (c) qPCR of cDNA. Standard curves were established. Utility of the assay was demonstrated in a pharmacokinetic study where all 12 samples for the blood concentration-time profile were obtained from a single mouse given an intravenous dose of 1 nmole siSurvivin (prepared as lipoplex with pegylated cationic liposomes). The RT-qPCR assay was sensitive (lower detection limit of 100 fM) and had a 5 * 107-fold dynamic range and low sample volume requirement (10 MUL). The 16-point standard curves constructed using whole blood samples were linear (R (2) > 0.98). The intraday and interday variations for the slopes were <=6%, although the variations for accuracy and precision at individual concentrations were substantially higher (58-145%). Standard curves prepared with water in place of blood showed similar results (<6% difference), indicating water may be used when blood is not available. The current RT-qPCR assay enabled the measurement of nonlabeled siRNA in small volume of blood samples. PMID- 26286677 TI - A Modeling and Simulation Framework for Adverse Events in Erlotinib-Treated Non Small-Cell Lung Cancer Patients. AB - Treatment with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor used for treating non-small-cell lung cancer (NSCLC) and other cancers, is frequently associated with adverse events (AE). We present a modeling and simulation framework for the most common erlotinib-induced AE, rash, and diarrhea, providing insights into erlotinib toxicity. We used the framework to investigate the safety of high-dose erlotinib pulses proposed to limit acquired resistance while treating NSCLC. Continuous-time Markov models were developed using rash and diarrhea AE data from 39 NSCLC patients treated with erlotinib (150 mg/day). Exposure and different covariates were investigated as predictors of variability. Rash was also tested as a survival predictor. Models developed were used in a simulation analysis to compare the toxicities of different regimens, including the previously mentioned pulsed strategy. Probabilities of experiencing rash or diarrhea were found to be highest early during treatment. Rash, but not diarrhea, was positively correlated with erlotinib exposure. In contrast with some common understandings, radiotherapy decreased transitioning to higher rash grades by 81% (p < 0.01), and experiencing rash was not correlated with positive survival outcomes. Model simulations predicted that the proposed pulsed regimen (1600 mg/week + 50 mg/day remaining week days) results in a maximum of 20% of the patients suffering from severe rash throughout the treatment course in comparison to 12% when treated with standard dosing (150 mg/day). In conclusion, the framework demonstrated that radiotherapy attenuates erlotinib-induced rash, providing an opportunity to use radiotherapy and erlotinib together, and demonstrated the tolerability of high-dose pulses intended to address acquired resistance to erlotinib. PMID- 26286678 TI - Risk factors for keratoconus in Israel: a case-control study. AB - PURPOSE: Keratoconus (KC) is a progressive corneal thinning disorder with an uncertain aetiology. Environmental and genetic factors, including consanguinity, eye rubbing and possibly sun exposure, play a role in the aetiology of KC. Here we test for risk factors for KC in an Israeli population with particular emphasis on sun exposure. METHODS: This case-control study included KC patients who were diagnosed at Care Laser Medical Group, a refractive surgery clinic with branches throughout Israel. The control group included age, sex and ethnicity matched individuals who were randomly selected from patients presenting at the clinic for refractive surgery, but without KC. Study subjects were asked to fill out a self administered questionnaire that included demographic and geographic details, questions on ocular and general health and sun exposure. Conditional logistic regression was used to analyse univariable and multivariable data to identify risk factors for KC. RESULTS: Seventy-three KC patients and 146 controls participated in the study. Univariable analyses demonstrated that eye rubbing [odds ratio (OR) = 3.76], positive family history of KC (OR = 6.10) and parents' education (<12 years, OR = 0.27, 0.23 for father's and mother's education respectively) were significant risk factors for KC. Univariable analyses of sun exposure behaviour during teenage years proved equivocal with some behaviours emerging as protective for KC (wearing a hat outdoors, OR = 3.13) or as risk factors (spending time in the shade, OR = 0.45), while others showed no association [limiting time in the sun (p = 0.51), and wearing sunglasses (p = 0.20)]. Most of the factors that were significant in the univariable analyses, also emerged as statistically significant in the multivariable model (OR = 3.37, 9.68, 0.35, 5.51 for eye rubbing, family history, parental education, wearing a hat outdoors, with the exception of spending time in the shade (p = 0.88). CONCLUSIONS: Eye rubbing, parents' education (as a measure of socio-economic status) and having family members with KC emerged as significant risk factors for KC. The role of sun exposure in KC remains equivocal and warrants further research. PMID- 26286679 TI - Coexistent lumbar spine disorders have a crucial impact on the clinical outcome after total hip replacement. AB - BACKGROUND: Degenerative hip and spine disease are known to frequently coexist. Lumbar spine disorders (LSDs), as opposed to other patient-related factors, are disregarded in the assessment of the clinical outcome after total hip replacement (THR). This prospective study investigates the influence of LSDs on the pre- and postoperative health-related quality of life and functional outcome of patients undergoing THR. METHODS: According to clearly defined criteria, 42 patients scheduled for cementless THR were assigned either to the LSD (13 patients with LSDs) or non-LSD group (29 patients without LSDs). A clinical assessment was performed preoperatively as well as 12, 24 and 60 months postoperatively using the Harris hip score (HHS), the Western Ontario and McMaster University osteoarthritis index (WOMAC) and the 36-item short form health survey (SF-36). RESULTS: The statistical analysis comparing the pre- and postoperative status within both groups showed an ongoing improvement of mean HHS and WOMAC after THR. The non-LSD group had a significantly higher postoperative HHS and WOMAC after 12, 24 and 60 months as well as SF-36 after 24 and 60 months. The LSD group improved significantly in the HHS at 24 and 60 months and the WOMAC at 12, 24 and 60 months postoperatively, whereas the SF-36 improvement was not significant. Comparison of preoperative data in both groups revealed a significantly higher SF 36 in the non-LSD group but no difference between the HHS and WOMAC. At each postoperative assessment, the HHS, WOMAC and SF-36, including its physical and mental health sum scores, were significantly higher in the non-LSD group, except for the WOMAC after 60 months. CONCLUSION: Owing to their crucial impact on hip function scores and health-related quality of life, it is recommended to consider LSDs preoperatively in studies dealing with the clinical outcome after THR. PMID- 26286680 TI - Neuroproteomic profiling of human body fluids. AB - Analysis of protein expression and abundance provides a possibility to extend the current knowledge on disease-associated processes and pathways. The human brain is a complex organ and dysfunction or damage can give rise to a variety of neurological diseases. Although many proteins potentially reflecting disease progress are originating from brain, the scarce availability of human tissue material has lead to utilization of body fluids such as cerebrospinal fluid and blood in disease-related research. Within the most common neurological disorders, much effort has been spent on studying the role of a few hallmark proteins in disease pathogenesis but despite extensive investigation, the signatures they provide seem insufficient to fully understand and predict disease progress. In order to expand the view the field of neuroproteomics has lately emerged alongside developing technologies, such as affinity proteomics and mass spectrometry, for multiplexed and high-throughput protein profiling. Here, we provide an overview of how such technologies have been applied to study neurological disease and we also discuss some important considerations concerning discovery of disease-associated profiles. PMID- 26286681 TI - Uncertainty and Expectation in Sentence Processing: Evidence From Subcategorization Distributions. AB - There is now considerable evidence that human sentence processing is expectation based: As people read a sentence, they use their statistical experience with their language to generate predictions about upcoming syntactic structure. This study examines how sentence processing is affected by readers' uncertainty about those expectations. In a self-paced reading study, we use lexical subcategorization distributions to factorially manipulate both the strength of expectations and the uncertainty about them. We compare two types of uncertainty: uncertainty about the verb's complement, reflecting the next prediction step; and uncertainty about the full sentence, reflecting an unbounded number of prediction steps. We find that uncertainty about the full structure, but not about the next step, was a significant predictor of processing difficulty: Greater reduction in uncertainty was correlated with increased reading times (RTs). We additionally replicated previously observed effects of expectation violation (surprisal), orthogonal to the effect of uncertainty. This suggests that both surprisal and uncertainty affect human RTs. We discuss the consequences for theories of sentence comprehension. PMID- 26286682 TI - Screening of ligninolytic fungi for biological pretreatment of lignocellulosic biomass. AB - To identify white rot fungi with high potential in biological pretreatment of lignocellulosic biomass, preliminary screening was carried out on plates by testing different strains for their ability to oxidize guaiacol and decolorize the dyes azure B and Poly R-478. Of the 86 strains screened, 16 were selected for secondary screening for their ligninolytic ability; however, low manganese peroxidase activity and no lignin peroxidase activity were detected. Strain BBEL0970 proved to be the most efficient in laccase production and was subsequently identified as Trametes versicolor by analysis of the ribosomal DNA internal transcribed spacer gene sequence. In combining laccase production with biological pretreatment, the replacement of glucose with barley straw significantly improved the laccase activity by up to 10.3 U/mL, which provided evidence toward potential utilization of barley straw in laccase production by BBEL0970. Simultaneously, comparison by thermogravimetric analysis of the untreated and pretreated barley straw in liquid fermentation of laccase also demonstrated the high potential of BBEL0970 in biological pretreatment of lignocellulosic biomass. This work sheds light on further exploration on the integrated process of low-cost laccase production and efficient biological pretreatment of barley straw by T. versicolor BBEL0970. PMID- 26286683 TI - Sample size calculation for meta-epidemiological studies. AB - Meta-epidemiological studies are used to compare treatment effect estimates between randomized clinical trials with and without a characteristic of interest. To our knowledge, there is presently nothing to help researchers to a priori specify the required number of meta-analyses to be included in a meta epidemiological study. We derived a theoretical power function and sample size formula in the framework of a hierarchical model that allows for variation in the impact of the characteristic between trials within a meta-analysis and between meta-analyses. A simulation study revealed that the theoretical function overestimated power (because of the assumption of equal weights for each trial within and between meta-analyses). We also propose a simulation approach that allows for relaxing the constraints used in the theoretical approach and is more accurate. We illustrate that the two variables that mostly influence power are the number of trials per meta-analysis and the proportion of trials with the characteristic of interest. We derived a closed-form power function and sample size formula for estimating the impact of trial characteristics in meta epidemiological studies. Our analytical results can be used as a 'rule of thumb' for sample size calculation for a meta-epidemiologic study. A more accurate sample size can be derived with a simulation study. PMID- 26286684 TI - Helping patients to reach decisions regarding their treatment: Do 'non-directive' approaches cause systematic bias? AB - OBJECTIVES: Many patients want help in considering medical information relevant to treatment decisions they have to make or agree to. The present research investigated whether focussing on particular issues relevant to a medical treatment decision (using an apparently non-directive procedure) could systematically bias a treatment decision. DESIGN AND METHODS: In a randomized design, participants (community volunteers, n = 146) were given standard information about treatment of cardiac risk factors by medication (statins). There were four experimental interventions in which the participants focussed on the likely personal relevance of subsets of the information previously given (positive, negative, or mixed aspects) or on irrelevant information. Participants were asked to rate their anticipated likelihood of accepting treatment before and after the experimental intervention. RESULTS: The rating of acceptance of treatment was significantly increased by positive focussing; negative focussing did not significantly alter the decision rating. CONCLUSIONS: The results partially replicate similar studies in health screening decisions. Reasons for the differences in results from those obtained in screening studies are considered. It is suggested that negative focussing may have less effect in decisions in which there are few risks. Statement of contribution What is already known on this subject? Decision-making in the context of health behaviour change has been widely described, but there are few experimental studies testing hypothesised strategies. 'Non-directiveness' is often regarded as desirable because it supposedly allows exploration of the decision without influencing it. Previous studies on health screening (but not treatment) have shown that health decision outcomes can be systematically influenced by the way in which a 'non directive' intervention is implemented. This can be accounted for by a modified subjective expected utility theory previously applied to both health screening and child vaccination decisions. What does this study add? The hypothetical decision about whether or not, in future, to take statins for elevated cholesterol levels was influenced by positive but not by negative focussing. Results were consistent with the theoretical framework. This study extends previous work on influences on the decision to undertake health screening and vaccination to treatment offered as secondary prevention. 'Non-directive' approaches to helping facilitate decisions can modify those decisions, and as such cannot be regarded as non-directive. PMID- 26286686 TI - 2015 RANZCOG Arthur Wilson Memorial Oration 'From little things, big things grow: The importance of periconception medicine'. AB - The time of our conception is when we are most vulnerable to survival and growing as a healthy human being. Genetic and environmental effects on gametes and the developing embryo can be literally life-and-death events with regard to the successful outcome of pregnancy. In the past decade, we have also understood that environmental factors under which the gametes grow and the embryo develops have lifelong implications with regard to developmental origins of health and disease. We now know that parenting begins before conception in that a compromised egg or sperm from either parent can alter the trajectory of development even if the embryo and intrauterine environment is optimal. There are now a large number of factors known to impact on the gametes to adversely affect them, including obesity, nutrition, cigarette smoking and environmental pollutants. The increasing use of in vitro fertilisation across the world exposes developing embryos to less than optimal environmental conditions through altered culture media, gases and potential pollutants from plastics, air and water. Many of these environmental exposures have not undergone experimental investigation and yet widely implemented in thousands of laboratories across the world. There have been many attempts to set up periconception planning either through the health service, the print and electronic media or through government action. We as a profession, as well as our Colleges, could do much better job in this area of preventative medicine by developing better guidelines and education for professional colleagues, the health service and the community. PMID- 26286685 TI - Interactive effects of BDNF Val66Met genotype and trauma on limbic brain anatomy in childhood. AB - Childhood trauma is a major precipitating factor in psychiatric disease. Emerging data suggest that stress susceptibility is genetically determined, and that risk is mediated by changes in limbic brain circuitry. There is a need to identify markers of disease vulnerability, and it is critical that these markers be investigated in childhood and adolescence, a time when neural networks are particularly malleable and when psychiatric disorders frequently emerge. In this preliminary study, we evaluated whether a common variant in the brain-derived neurotrophic factor (BDNF) gene (Val66Met; rs6265) interacts with childhood trauma to predict limbic gray matter volume in a sample of 55 youth high in sociodemographic risk. We found trauma-by-BDNF interactions in the right subcallosal area and right hippocampus, wherein BDNF-related gray matter changes were evident in youth without histories of trauma. In youth without trauma exposure, lower hippocampal volume was related to higher symptoms of anxiety. These data provide preliminary evidence for a contribution of a common BDNF gene variant to the neural correlates of childhood trauma among high-risk urban youth. Altered limbic structure in early life may lay the foundation for longer term patterns of neural dysfunction, and hold implications for understanding the psychiatric and psychobiological consequences of traumatic stress on the developing brain. PMID- 26286687 TI - Using short vignettes to disentangle perceived capability from motivation: a test using walking and resistance training behaviors. AB - Self-efficacy is arguably the strongest correlate of physical activity, yet some researchers suggest this is because the construct confounds ability with motivation. We examine a more circumscribed construct, called perceived capability (PC), meant to measure ability but not motivation and propose that the construct will not be related to unskilled physical activities but may be linked to skilled behaviors. The purpose of this paper was to examine whether a PC construct can be stripped of motivation using a vignette approach in both walking and resistance training behaviors. Participants were a random sample of 248 university students, who were then randomly assigned to either answer resistance training or walking behavior questions. Both groups completed a PC measure and reasons for their answer before and after reading a vignette that clarified the phrasing of capability to a literal use of the term. PC was significantly (p < .01) higher post- compared to pre-vignette and the differences were greater (p < .01) for walking than for resistance training. PC had significantly (p < .01) smaller correlations with intention and self-reported behavior post disambiguation, which resulted in a null relationship with walking but a small correlation with resistance training behavior. When PC was combined with intention to predict behavior, however, there was no significant (p > .05) difference in the amount of variance explained pre- to post-vignette. Thought listing showed that participants did not report capability barriers to walking and over half of the sample construed capability as motivation/other priorities pre-vignette. The findings support use of a vignette approach for researchers who wish to disentangle the assessment of PC from motivation while creating no overall loss in explained variance of physical activity. PMID- 26286688 TI - Increased Likelihood of Missed Appointments ("No Shows") for Racial/Ethnic Minorities in a Safety Net Health System. AB - Missed appointments have been linked to adverse outcomes known to affect racial/ethnic minorities. However, the association of missed appointments with race/ethnicity has not been determined. We sought to determine the relationships between race/ethnicity and missed appointments by performing a cross-sectional study of 161 350 patients in a safety net health system. Several race/ethnicity categories were significantly associated with missed appointment rates, including Hispanic/Latino patients, American Indian/Alaskan Native patients, and Black/African American patients, as compared with White non-Hispanic patients. Other significant predictors included Mexico as country of origin, medical complexity, and major mental illness. We recommend additional research to determine which interventions best reduce missed appointments for minority populations in order to improve the care of vulnerable patients. PMID- 26286689 TI - Single-Molecule Real-Time Sequencing Combined with Optical Mapping Yields Completely Finished Fungal Genome. AB - Next-generation sequencing (NGS) technologies have increased the scalability, speed, and resolution of genomic sequencing and, thus, have revolutionized genomic studies. However, eukaryotic genome sequencing initiatives typically yield considerably fragmented genome assemblies. Here, we assessed various state of-the-art sequencing and assembly strategies in order to produce a contiguous and complete eukaryotic genome assembly, focusing on the filamentous fungus Verticillium dahliae. Compared with Illumina-based assemblies of the V. dahliae genome, hybrid assemblies that also include PacBio-generated long reads establish superior contiguity. Intriguingly, provided that sufficient sequence depth is reached, assemblies solely based on PacBio reads outperform hybrid assemblies and even result in fully assembled chromosomes. Furthermore, the addition of optical map data allowed us to produce a gapless and complete V. dahliae genome assembly of the expected eight chromosomes from telomere to telomere. Consequently, we can now study genomic regions that were previously not assembled or poorly assembled, including regions that are populated by repetitive sequences, such as transposons, allowing us to fully appreciate an organism's biological complexity. Our data show that a combination of PacBio-generated long reads and optical mapping can be used to generate complete and gapless assemblies of fungal genomes. IMPORTANCE: Studying whole-genome sequences has become an important aspect of biological research. The advent of next-generation sequencing (NGS) technologies has nowadays brought genomic science within reach of most research laboratories, including those that study nonmodel organisms. However, most genome sequencing initiatives typically yield (highly) fragmented genome assemblies. Nevertheless, considerable relevant information related to genome structure and evolution is likely hidden in those nonassembled regions. Here, we investigated a diverse set of strategies to obtain gapless genome assemblies, using the genome of a typical ascomycete fungus as the template. Eventually, we were able to show that a combination of PacBio-generated long reads and optical mapping yields a gapless telomere-to-telomere genome assembly, allowing in-depth genome analyses to facilitate functional studies into an organism's biology. PMID- 26286690 TI - The Reemergent 1977 H1N1 Strain and the Gain-of-Function Debate. AB - The 1977-1978 influenza epidemic was probably not a natural event, as the genetic sequence of the virus was nearly identical to the sequences of decades-old strains. While there are several hypotheses that could explain its origin, the possibility that the 1977 epidemic resulted from a laboratory accident has recently gained popularity in discussions about the biosafety risks of gain-of function (GOF) influenza virus research, as an argument for why this research should not be performed. There is now a moratorium in the United States on funding GOF research while the benefits and risks, including the potential for accident, are analyzed. Given the importance of this historical epidemic to ongoing policy debates, we revisit the evidence that the 1977 epidemic was not natural and examine three potential origins: a laboratory accident, a live vaccine trial escape, or deliberate release as a biological weapon. Based on available evidence, the 1977 strain was indeed too closely matched to decades-old strains to likely be a natural occurrence. While the origin of the outbreak cannot be conclusively determined without additional evidence, there are very plausible alternatives to the laboratory accident hypothesis, diminishing the relevance of the 1977 experience to the modern GOF debate. PMID- 26286691 TI - Sup35p in Its Soluble and Prion States Is Packaged inside Extracellular Vesicles. AB - The yeast Saccharomyces cerevisiae harbors several prions that constitute powerful models to investigate the mechanisms of epigenetic structural inheritance. [PSI(+)] is undoubtedly the best-known yeast prion and results from the conversion of the translation termination factor Sup35p into self perpetuating protein aggregates. Structurally different conformers of Sup35p aggregates can lead to [PSI(+)] strains with weak or strong prion phenotypes. Yeast prions are faithfully transmitted from mother to daughter cells during cell division, upon cytoplasmic mixing during mating, or when Sup35p fibrils made in test tubes are introduced into spheroplasts. Virtually all living cells in the three domains of life, Bacteria, Archaea, and Eukarya, secrete small membrane vesicles in the extracellular space. These extracellular vesicles (EV) have gained increasing interest as vehicles for the intercellular transfer of signaling molecules, nucleic acids, and pathogenic factors, as well as prion-like protein aggregates associated with neurodegenerative diseases. To begin to explore the question of whether EV could represent a natural mean for yeast prion transmission from cell to cell, we purified these extracellular vesicles and assessed whether they contained Sup35p. Here, we show that Sup35p is secreted within EV released in the extracellular medium of yeast cultures. We demonstrate that Sup35p within EV isolated from strong and weak [PSI(+)] cells is in an infectious prion conformation. Among the possible implications of our work is the possibility of previously unsuspected EV-mediated horizontal cell-to-cell transfer of fungal prions. IMPORTANCE: Most living cells in the three domains of life, Bacteria, Archaea, and Eukarya, secrete small membrane vesicles in the extracellular space. These extracellular vesicles (EV) were long viewed as "trash cans" by which cells disposed of unwanted macromolecules. EV gained renewed interest as their roles as vehicles for the cell-to-cell transfer of nucleic acids, signaling molecules, and pathogenic factors were recently uncovered. Of particular interest is their proposed role in the prion-like propagation of toxic protein aggregates in neurodegenerative diseases. Yeasts naturally harbor prion proteins that are excellent models to investigate the mechanisms of formation, propagation, and elimination of self-perpetuating protein aggregates. Here we show for the first time that a yeast prion is secreted within EV in its infectious aggregated state. A major implication of our work is the possibility of EV-mediated horizontal spread of fungal prions. PMID- 26286692 TI - Remodeling of the Z-Ring Nanostructure during the Streptococcus pneumoniae Cell Cycle Revealed by Photoactivated Localization Microscopy. AB - Ovococci form a morphological group that includes several human pathogens (enterococci and streptococci). Their shape results from two modes of cell wall insertion, one allowing division and one allowing elongation. Both cell wall synthesis modes rely on a single cytoskeletal protein, FtsZ. Despite the central role of FtsZ in ovococci, a detailed view of the in vivo nanostructure of ovococcal Z-rings has been lacking thus far, limiting our understanding of their assembly and architecture. We have developed the use of photoactivated localization microscopy (PALM) in the ovococcus human pathogen Streptococcus pneumoniae by engineering spDendra2, a photoconvertible fluorescent protein optimized for this bacterium. Labeling of endogenously expressed FtsZ with spDendra2 revealed the remodeling of the Z-ring's morphology during the division cycle at the nanoscale level. We show that changes in the ring's axial thickness and in the clustering propensity of FtsZ correlate with the advancement of the cell cycle. In addition, we observe double-ring substructures suggestive of short lived intermediates that may form upon initiation of septal cell wall synthesis. These data are integrated into a model describing the architecture and the remodeling of the Z-ring during the cell cycle of ovococci. IMPORTANCE: The Gram positive human pathogen S. pneumoniae is responsible for 1.6 million deaths per year worldwide and is increasingly resistant to various antibiotics. FtsZ is a cytoskeletal protein polymerizing at midcell into a ring-like structure called the Z-ring. FtsZ is a promising new antimicrobial target, as its inhibition leads to cell death. A precise view of the Z-ring architecture in vivo is essential to understand the mode of action of inhibitory drugs (see T. den Blaauwen, J. M. Andreu, and O. Monasterio, Bioorg Chem 55:27-38, 2014, doi:10.1016/j.bioorg.2014.03.007, for a review on FtsZ inhibitors). This is notably true in ovococcoid bacteria like S. pneumoniae, in which FtsZ is the only known cytoskeletal protein. We have used superresolution microscopy to obtain molecular details of the pneumococcus Z-ring that have so far been inaccessible with conventional microscopy. This study provides a nanoscale description of the Z-ring architecture and remodeling during the division of ovococci. PMID- 26286693 TI - An Alternative Terminal Step of the General Secretory Pathway in Staphylococcus aureus. AB - Type I signal peptidase (SPase) is essential for viability in wild-type bacteria because the terminal step of the bacterial general secretory pathway requires its proteolytic activity to release proteins from their membrane-bound N-terminal leader sequences after translocation across the cytoplasmic membrane. Here, we identify the Staphylococcus aureus operon ayrRABC (SA0337 to SA0340) and show that once released from repression by AyrR, the protein products AyrABC together confer resistance to the SPase inhibitor arylomycin M131 by providing an alternate and novel method of releasing translocated proteins. Thus, the derepression of ayrRABC allows cells to bypass the essentiality of SPase. We demonstrate that AyrABC functionally complements SPase by mediating the processing of the normally secreted proteins, albeit in some cases with reduced efficiency and either without cleavage or via cleavage at a site N-terminal to the canonical SPase cleavage site. Thus, ayrRABC encodes a secretion stress inducible alternate terminal step of the general secretory pathway. IMPORTANCE : Addressing proteins for proper localization within or outside a cell in both eukaryotes and prokaryotes is often accomplished with intrinsic signals which mediate membrane translocation and which ultimately must be removed. The canonical enzyme responsible for the removal of translocation signals is bacterial type I signal peptidase (SPase), which functions at the terminal step of the general secretory pathway and is thus essential in wild-type bacteria. Here, we identify a four-gene operon in S. aureus that encodes an alternate terminal step of the general secretory pathway and thus makes SPase nonessential. The results have important implications for protein secretion in bacteria and potentially for protein trafficking in prokaryotes and eukaryotes in general. PMID- 26286695 TI - The Justification for the Academy Track in mBio. PMID- 26286694 TI - New Insight into Filamentous Hemagglutinin Secretion Reveals a Role for Full Length FhaB in Bordetella Virulence. AB - Bordetella filamentous hemagglutinin (FHA), a primary component of acellular pertussis vaccines, contributes to virulence, but how it functions mechanistically is unclear. FHA is first synthesized as an ~370-kDa preproprotein called FhaB. Removal of an N-terminal signal peptide and a large C-terminal prodomain (PD) during secretion results in "mature" ~250-kDa FHA, which has been assumed to be the biologically active form of the protein. Deletion of two C terminal subdomains of FhaB did not affect production of functional FHA, and the mutant strains were indistinguishable from wild-type bacteria for their ability to adhere to the lower respiratory tract and to suppress inflammation in the lungs of mice. However, the mutant strains, which produced altered FhaB molecules, were eliminated from the lower respiratory tract much faster than wild type B. bronchiseptica, suggesting a defect in resistance to early immune mediated clearance. Our results revealed, unexpectedly, that full-length FhaB plays a critical role in B. bronchiseptica persistence in the lower respiratory tract. IMPORTANCE: The Bordetella filamentous hemagglutinin (FHA) is a primary component of the acellular pertussis vaccine and an important virulence factor. FHA is initially produced as a large protein that is processed during secretion to the bacterial surface. As with most processed proteins, the mature form of FHA has been assumed to be the functional form of the protein. However, our results indicate that the full-length form plays an essential role in virulence in vivo. Furthermore, we have found that FHA contains intramolecular regulators of processing and that this control of processing is integral to its virulence activities. This report highlights the advantage of studying protein maturation and function simultaneously, as a role for the full-length form of FHA was evident only from in vivo infection studies and not from in vitro studies on the production or maturation of FHA or even from in vitro virulence-associated activity assays. PMID- 26286696 TI - An Ounce of Tat Prevention Is Worth a Pound of Functional Cure. PMID- 26286697 TI - Deriving C4 photosynthetic parameters from combined gas exchange and chlorophyll fluorescence using an Excel tool: theory and practice. AB - The higher photosynthetic potential of C4 plants has led to extensive research over the past 50 years, including C4 -dominated natural biomes, crops such as maize, or for evaluating the transfer of C4 traits into C3 lineages. Photosynthetic gas exchange can be measured in air or in a 2% Oxygen mixture using readily available commercial gas exchange and modulated PSII fluorescence systems. Interpretation of these data, however, requires an understanding (or the development) of various modelling approaches, which limit the use by non specialists. In this paper we present an accessible summary of the theory behind the analysis and derivation of C4 photosynthetic parameters, and provide a freely available Excel Fitting Tool (EFT), making rigorous C4 data analysis accessible to a broader audience. Outputs include those defining C4 photochemical and biochemical efficiency, the rate of photorespiration, bundle sheath conductance to CO2 diffusion and the in vivo biochemical constants for PEP carboxylase. The EFT compares several methodological variants proposed by different investigators, allowing users to choose the level of complexity required to interpret data. We provide a complete analysis of gas exchange data on maize (as a model C4 organism and key global crop) to illustrate the approaches, their analysis and interpretation. (c) 2015 John Wiley & Sons Ltd. PMID- 26286698 TI - Multiple sclerosis patients have a diminished serologic response to vitamin D supplementation compared to healthy controls. AB - BACKGROUND: Vitamin D insufficiency is a risk factor for multiple sclerosis (MS), and patients do not always show the expected response to vitamin D supplementation. OBJECTIVE: We aimed to determine if vitamin D supplementation leads to a similar increase in serum 25-hydroxyvitamin-D (25(OH)D) levels in patients with MS and healthy controls (HCs). METHODS: Participants in this open label study were female, white, aged 18-60 years, had 25(OH)D levels ? 75 nmol/l at screening, and had relapsing-remitting MS (RRMS) or were HCs. Participants received 5000 IU/day of vitamin D3 for 90 days. Utilizing generalized estimating equations we examined the relationship between the primary outcome (serum 25(OH)D level) and the primary (MS versus HC status) and secondary predictors. RESULTS: For this study 27 MS patients and 30 HCs were enrolled. There was no significant difference in baseline 25(OH)D level or demographics except for higher body mass index (BMI) in the MS group (25.3 vs. 23.6 kg/m(2), p=0.035). In total, 24 MS subjects and 29 HCs completed the study. In a multivariate model accounting for BMI, medication adherence, and oral contraceptive use, MS patients had a 16.7 nmol/l (95%CI: 4.2, 29.2, p=0.008) lower increase in 25(OH)D levels compared with HCs. CONCLUSIONS: Patients with MS had a lower increase in 25(OH)D levels with supplementation, even after accounting for putative confounders. PMID- 26286699 TI - Pixantrone: a B-cell-depleting immunosuppressant for multiple sclerosis patients with active disease. AB - BACKGROUND: Mitoxantrone has been approved for patients with worsening relapsing remitting (RR) or secondary progressive multiple sclerosis (SPMS), but its long term use is limited by its cardiotoxicity. Pixantrone (PIX) is an analog of mitoxantrone. OBJECTIVES: The aim of this open-label, multicenter, noncomparative Phase I/II trial was to explore the immunosuppressive effect of PIX, its impact on clinical disease activity and cerebral gadolinium-enhanced (Gd(+)) lesions, and its safety. METHODS: Eighteen patients with active RRMS and SPMS (? 1 cerebral Gd(+) lesion) despite approved immunomodulatory therapy received four intravenous PIX injections every 21 days. A neurological examination, hematology, lymphocyte subsets, and biochemistry were performed at Day 1, Weeks 3, 6 and 9, and Months 3, 6, 9 and 12. Echocardiography was performed before each infusion, at Months 3, 6 and 12. Cerebral MRI was performed at baseline, and at Months 6 and 12. RESULTS: CD19+ cells were reduced by 95% at Month 3 and by 47% at Month 12. Gd+ lesions were reduced by 86% at Month 12 (p = 0.01). The annual relapse rate was reduced by 87% (p < 10(-4)). Two patients experienced a transient reduction in left ventricular fraction. CONCLUSION: These preliminary data indicate the efficacy of PIX in active RRMS and SPMS. PMID- 26286700 TI - Over-the-counter anti-oxidant therapies for use in multiple sclerosis: A systematic review. AB - BACKGROUND: Anti-oxidant compounds that are found in over-the-counter (OTC) supplements and foods are gaining interest as treatments for multiple sclerosis (MS). They are widely used by patients, sometimes without a clear evidence base. OBJECTIVE: We conducted a systematic review of animal and clinical research to determine the evidence for the benefits of OTC anti-oxidants in MS. METHODS: Using predefined criteria, we searched key databases. Two authors scrutinized all studies against inclusion/exclusion criteria, assessed study risk-of-bias and extracted results. RESULTS: Of the 3507 titles, 145 met criteria and included compounds, alpha(alpha)-lipoic acid (ALA), anti-oxidant vitamins, Ginkgo biloba, quercetin, resveratrol and epigallocatechin-3-gallate (ECGC). The strongest evidence to support OTC anti-oxidants was for compounds EGCG and ALA in animal models; both consistently showed anti-inflammatory/anti-oxidant effects and reduced neurological impairment. Only vitamin E, Ginkgo biloba and ALA were examined for efficacy in pilot clinical trials with either conflicting evidence or evidence of no benefit. CONCLUSION: OTC anti-oxidants EGCG and ALA show the most consistent benefit, however only in preclinical studies. There is no evidence that they alter MS relapses or progression. Future work should focus on testing more of these therapies for clinical efficacy before recommending them to MS patients. PMID- 26286701 TI - Regional hippocampal involvement and cognitive impairment in pediatric multiple sclerosis. AB - OBJECTIVES: We assessed global and regional hippocampal volume abnormalities in pediatric multiple sclerosis (MS) patients and their correlations with clinical, neuropsychological and magnetic resonance imaging metrics. METHODS: From 53 pediatric MS patients and 18 healthy controls, global hippocampal volume was computed using a manual tracing procedure. Regional hippocampal volume modifications were assessed using a radial mapping analysis. MS patients with abnormal performance in three or more tests of a neuropsychological battery for children were classified as cognitively impaired. RESULTS: Global hippocampal volume was reduced in MS patients compared with controls, but did not correlate with clinical, neuropsychological and magnetic resonance imaging measures. Compared to controls, MS patients experienced bilateral radial atrophy of the cornu ammonis, subiculum and dentate gyrus subfields as well as radial hypertrophy of the dentate gyrus subfield. Regional hippocampal volume modifications correlated with brain T2 lesion volume as well as attention and language abilities. Global hippocampal volume did not differ between cognitively impaired (n=12) and cognitively preserved MS patients. Compared to cognitively preserved, cognitively impaired MS patients had atrophy of the subiculum and dentate gyrus subfields of the right hippocampus. CONCLUSIONS: Hippocampal subregions have different vulnerability to damage in pediatric MS. Regional rather than global hippocampal involvement contributes to global cognitive impairment as well as to deficits of selected cognitive tests. PMID- 26286702 TI - The mechanism of Rubisco-catalysed oxygenation. AB - Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is the cornerstone of photosynthetic carbon assimilation because it catalyses the fixation of CO2 onto ribulose-1,5-bisphosphate (RuBP). The enzyme also catalyses RuBP oxygenation, thereby evolving phosphoglycolate which is recycled along the photorespiratory pathway. Oxygenation is quantitatively important, because under ordinary gaseous conditions, more than one third of RuBP molecules are oxygenated rather than carboxylated. However, contrary to carboxylation, the chemical mechanism of oxygenation is not well known, and little progress has been made since the early 80s. Here, I review recent experimental data that provide some new insights into the reaction mechanism, and carry out simple calculations of kinetic parameters. Isotope effects suggest that oxygenation is less likely initiated by a redox phenomenon (such as superoxide production) and more likely involves concerted chemical events that imply interactions with protons. A possible energy profile of the reaction is drawn which suggests that the generation of the oxygenated reaction intermediate (peroxide) is irreversible. Possible changes in oxygenation associated rate constants between Rubisco forms are discussed. PMID- 26286703 TI - Impact of lithium alone or in combination with haloperidol on oxidative stress parameters and cell viability in SH-SY5Y cell culture. AB - BACKGROUND: It has been reported that lithium may inhibit lipid peroxidation and protein oxidation. Lithium salts also appear to stimulate cell proliferation, increase neurogenesis, and delay cell death. Oxidative stress and neurodegeneration may play an important role in the pathophysiology of bipolar disorder and the disease course thereof. The aim of this research is to estimate the influence of lithium (alone and in combination with haloperidol) on the parameters of oxidative stress and viability of SH-SY5Y cell lines in neutral and pro-oxidative conditions. METHODS: The evaluated oxidative stress parameter was lipid peroxidation. The viability of the cell lines was measured utilising the MTT test. RESULTS: In neutral conditions, higher levels of thiobarbituric acid reactive substances were observed in those samples which contained both haloperidol and lithium than in other samples. However, these differences were not statistically significant. Cell viability was significantly higher in therapeutic lithium samples than in the controls; samples of haloperidol alone as well as those of haloperidol with lithium did not differ from controls. CONCLUSIONS: The results of our study may indicate that lithium possess neuroprotective properties that may be partly due to antioxidative effects. The combination of lithium and haloperidol may generate increased oxidative stress. PMID- 26286704 TI - Orthopedic Injuries and Their Treatment in Children During Earthquakes: A Systematic Review. AB - Orthopedic injuries commonly affect children during earthquakes, but reports about them are rare. This setting may lead to different standards of care, but guidelines are still missing in this field. A systematic review was performed to: (1) assess type and body distribution of pediatric earthquake-related injuries, treatment performed, length of stay, and complications; and (2) identify starting points to define standards of care. PubMed database was researched for papers (1999-2014 period) in agreement with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. Inclusion criteria were: English, French, Spanish, or Italian language and data reported about orthopedic lesions in children (<=18 years old). Reviews, letters, commentaries, editorials, and single case reports were excluded. Two independent reviewers selected articles after abstract and full-text reading. Traumatic injuries caused child hospital admissions ranging from 46.9% to 100.0%; 16% to 53% suffered fractures. Lower limbs mostly were involved. Soft-tissue injuries affected 55% of patients. Debridement and external fixation (EF) were the most frequent surgical treatments. Amputation rates varied from 5% to 11%. This study revealed that field hospitals should be prepared to: (1) treat mainly lower extremities fractures in children; and (2) use especially EF techniques. The presence of orthopedic surgeons familiar with pediatric traumatology should be considered. PMID- 26286705 TI - Numerous Iron-Rich Particles Lie on the Surface of Erionite Fibers from Rome (Oregon, USA) and Karlik (Cappadocia, Turkey). AB - Erionite samples from Rome, Oregon (USA) and Karlik, Cappadocia (Turkey) were analyzed by environmental scanning electron microscopy (E-SEM) coupled with energy-dispersive spectroscopy (EDS) to verify the chemical composition of this mineral phase, and the presence of iron in particular. By means of backscattered electron images, a large number of particles/grains were observed on the surface of the erionite fibers from both locations. The particles were found to be micrometric on samples from Rome and submicrometric on samples from Karlik, and always lighter than the hosting crystal in appearance. In different areas of the same fiber or bundle of fibers, several EDS spectra were recorded. Iron was detected only when a light particle was lying in the path of the electron beam. Iron was never identified in the EDS spectra acquired on the flat erionite surface. The results from E-SEM/EDS were confirmed by micro-Raman spectroscopy, showing bands ascribing to hematite-Fe2O3, goethite-FeO(OH), or jarosite KFe3(3+)(SO4)2(OH)6 when the laser beam was addressed on the light particles observed on the fiber surface. The evidence that iron is on the surface of erionite fibers, rather than being part of the crystalline structure, may be relevant for the carcinogenic potential of these fibers. PMID- 26286706 TI - Optimization of intermittent microwave-convective drying using response surface methodology. AB - In this study, response surface methodology was used for optimization of intermittent microwave-convective air drying (IMWC) parameters with employing desirability function. Optimization factors were air temperature (40-80 degrees C), air velocity (1-2 m/sec), pulse ratio) PR ((2-6), and microwave power (200 600 W) while responses were rehydration ratio, bulk density, total phenol content (TPC), color change, and energy consumption. Minimum color change, bulk density, energy consumption, maximum rehydration ratio, and TPC were assumed as criteria for optimizing drying conditions of apple slices in IMWC. The optimum values of process variables were 1.78 m/sec air velocity, 40 degrees C air temperature, PR 4.48, and 600 W microwave power that characterized by maximum desirability function (0.792) using Design expert 8.0. The air temperature and microwave power had significant effect on total responses, but the role of air velocity can be ignored. Generally, the results indicated that it was possible to obtain a higher desirability value if the microwave power and temperature, respectively, increase and decrease. PMID- 26286707 TI - Specific exercise training for reducing neck and shoulder pain among military helicopter pilots and crew members: a randomized controlled trial protocol. AB - BACKGROUND: Flight-related neck/shoulder pain is frequent among military helicopter pilots and crew members. With a lifetime prevalence of 81% for pilots and 84% for crew members, the prevalence of neck pain is considered high compared to the general population. The aim of this study was to investigate whether a specifically tailored exercise intervention would reduce the prevalence and incidence rate of neck/shoulder pain among helicopter pilots and crew members. METHOD: This study used a prospective, parallel group, single blinded, randomized controlled design. Participants were military helicopter pilots and crew members recruited from the Royal Danish Air Force. Inclusion criteria were: 1) employed within the Royal Danish Air Force as a helicopter pilot or onboard crew member (technician, systems-operator, tactical helicopter observer and/or navigator), 2) maintaining operational flight status at enrollment, and 3) operational flying within the previous 6 months. Primary outcome was change in neck and shoulder pain assessed by 1) a modified version of the "Standardized Nordic questionnaire for the analysis of musculoskeletal symptoms" and by 2) pressure pain threshold measurements. Secondary outcomes included: postural balance, strength, stability, and rate of force development for neck and shoulder muscles. Measurements at baseline and follow-up were conducted at four air force bases in Denmark. Sixty nine participants were individually randomized to either a training group (TG) or a reference group (RG). Participants in the TG performed 20-weeks of physical exercise training divided into sessions of 3 * 20 min per week. Training was completed within working hours and consisted of specific exercise training for the neck and shoulder muscles based on the principles of "Intelligent Physical Exercise Training". The RG received no training. DISCUSSION: In spite of the high prevalence of flight related neck/shoulder pain among military helicopter pilots and crew members there are currently no evidence based guidelines for the prevention or clinical handling of neck pain among these occupational groups. Results from this study may therefore be beneficial for future establishment of such guidelines. TRIAL REGISTRATION: Ethical committee of Southern Denmark (S 20120121) 29 August, 2012. Clinical Trail Registration (NCT01926262) 16 August, 2013. PMID- 26286708 TI - Improved Model for Predicting the Free Energy Contribution of Dinucleotide Bulges to RNA Duplex Stability. AB - Predicting the secondary structure of RNA is an intermediate in predicting RNA three-dimensional structure. Commonly, determining RNA secondary structure from sequence uses free energy minimization and nearest neighbor parameters. Current algorithms utilize a sequence-independent model to predict free energy contributions of dinucleotide bulges. To determine if a sequence-dependent model would be more accurate, short RNA duplexes containing dinucleotide bulges with different sequences and nearest neighbor combinations were optically melted to derive thermodynamic parameters. These data suggested energy contributions of dinucleotide bulges were sequence-dependent, and a sequence-dependent model was derived. This model assigns free energy penalties based on the identity of nucleotides in the bulge (3.06 kcal/mol for two purines, 2.93 kcal/mol for two pyrimidines, 2.71 kcal/mol for 5'-purine-pyrimidine-3', and 2.41 kcal/mol for 5' pyrimidine-purine-3'). The predictive model also includes a 0.45 kcal/mol penalty for an A-U pair adjacent to the bulge and a -0.28 kcal/mol bonus for a G-U pair adjacent to the bulge. The new sequence-dependent model results in predicted values within, on average, 0.17 kcal/mol of experimental values, a significant improvement over the sequence-independent model. This model and new experimental values can be incorporated into algorithms that predict RNA stability and secondary structure from sequence. PMID- 26286710 TI - Daily consumption of a mangosteen-based drink improves in vivo antioxidant and anti-inflammatory biomarkers in healthy adults: a randomized, double-blind, placebo-controlled clinical trial. AB - Mangosteen (Garcinia mangostana) is a tropical fruit cultivated mainly in Southeast Asia. Recent studies have shown mangosteen has many health benefits. In this study, we aimed to determine the effects of a mangosteen-based beverage on antioxidant and anti-inflammatory and immunity biomarkers in plasma of healthy adults. A randomized, double-blind, placebo-controlled clinical trial was conducted using 60 participants, 30 men, and 30 women, ages 18-60. Participants were randomly divided into two groups, placebo and mangosteen groups, with the same number of male and female participants in each group. The trial duration was 30 days. ORAC as an antioxidant biomarker was measured in both groups. It was found that after the 30-day trial, the group given the mangosteen-based drink formula showed 15% more antioxidant capacity in the bloodstream than did the placebo group. As for the inflammatory biomarkers, in the mangosteen group, between the preintervention and postintervention, the C-reactive protein level significantly decreased by 46%, while no significant decreases for the same biomarker was observed in the placebo group. Immunity biomarkers IgA, IgG, IgM, C3 and C4 were not affected in either group. In addition, the effects on hepatic function (Aspartate Aminotransferase and Alanine Aminotransferase) and kidney function (creatinine) were investigated. Our results indicated that after the 30 day consumption of the beverage, there were no side effects on human hepatic and kidney functions. The outcome of this study showed that the mangosteen-based formula significantly increases antioxidant capacity and possesses anti inflammatory benefits with no side effects on immune, hepatic, and renal functions for long-term consumption. PMID- 26286711 TI - Active Targeted Nanoparticles for Oral Administration of Gastric Cancer Therapy. AB - Gastric carcinogenesis is a commonly diagnosed type of cancer and has a dismal prognosis because of the rate at which it aggressively spreads and because of the lack of effective therapies to stop its progression. This study evaluated a type of oral drug delivery system of a potential target-activated nanosizer comprising a fucose-conjugated chitosan and polyethylene glycol-conjugated chitosan complex with gelatin containing encapsulated green tea polyphenol extract epigallocatechin-3-gallate, allowing oral administration of the drug through a site-specific release in gastric cancer cells. The results demonstrated that the nanoparticles effectively reduced drug release within gastric acids and that a controlled epigallocatechin-3-gallate release inhibited gastric cancer cell growth, induced cell apoptosis, and reduced vascular endothelial growth factor protein expression. Furthermore, in vivo assay results indicated that the prepared epigallocatechin-3-gallate-loaded fucose-chitosan/polyethylene glycol chitosan/gelatin nanoparticles significantly affected gastric tumor activity and reduced gastric and liver tissue inflammatory reaction in an orthotopic gastric tumor mouse model. PMID- 26286709 TI - Effortful Control Predicts Adolescent Antisocial-Aggressive Behaviors and Depressive Symptoms: Co-Occurrence and Moderation by Impulsivity. AB - Effortful control is associated with fewer aggressive-antisocial behaviors (AAB) and depressive symptoms (DEP), but impulsivity may moderate these relations. However, few researchers have considered the effects of AAB-DEP co-occurrence. A multi-informant, multimethod approach assessed 5- to 10-year-olds' effortful control and impulsivity and, 5-6 years later, their AAB and DEP (N = 474). Participants were non-Hispanic Caucasian (59.2%) or Hispanic (27.9%) from a Southwestern U.S. metropolitan area. Low effortful control predicted pure AAB. Low effortful control and low impulsivity predicted pure DEP and co-occurring AAB DEP. An effortful Control * Impulsivity * Age interaction predicted pure AAB and co-occurring AAB-DEP. For older adolescents, lower effortful control predicted more symptoms only at average and high impulsivity. Results highlight multiple pathways to pure DEP versus pure AAB or co-occurring AAB-DEP. PMID- 26286712 TI - Administrative health data in Canada: lessons from history. AB - BACKGROUND: Health decision-making requires evidence from high-quality data. As one example, the Discharge Abstract Database (DAD) compiles data from the majority of Canadian hospitals to form one of the most comprehensive and highly regarded administrative health databases available for health research, internationally. However, despite the success of this and other administrative health data resources, little is known about their history or the factors that have led to their success. The purpose of this paper is to provide an historical overview of Canadian administrative health data for health research to contribute to the institutional memory of this field. METHODS: We conducted a qualitative content analysis of approximately 20 key sources to construct an historical narrative of administrative health data in Canada. Specifically, we searched for content related to key events, individuals, challenges, and successes in this field over time. RESULTS: In Canada, administrative health data for health research has developed in tangent with provincial research centres. Interestingly, the lessons learned from this history align with the original recommendations of the 1964 Royal Commission on Health Services: (1) standardization, and (2) centralization of data resources, that is (3) facilitated through governmental financial support. CONCLUSIONS: The overview history provided here illustrates the need for longstanding partnerships between government and academia, for classification, terminology and standardization are time-consuming and ever-evolving processes. This paper will be of interest to those who work with administrative health data, and also for countries that are looking to build or improve upon their use of administrative health data for decision-making. PMID- 26286713 TI - Substance misuse and older people: better information, better care. PMID- 26286714 TI - Response to 'Body mass index and the risk of rheumatoid arthritis: a systematic review and dose-response meta-analysis'. PMID- 26286716 TI - Molgenis-impute: imputation pipeline in a box. AB - BACKGROUND: Genotype imputation is an important procedure in current genomic analysis such as genome-wide association studies, meta-analyses and fine mapping. Although high quality tools are available that perform the steps of this process, considerable effort and expertise is required to set up and run a best practice imputation pipeline, particularly for larger genotype datasets, where imputation has to scale out in parallel on computer clusters. RESULTS: Here we present MOLGENIS-impute, an 'imputation in a box' solution that seamlessly and transparently automates the set up and running of all the steps of the imputation process. These steps include genome build liftover (liftovering), genotype phasing with SHAPEIT2, quality control, sample and chromosomal chunking/merging, and imputation with IMPUTE2. MOLGENIS-impute builds on MOLGENIS-compute, a simple pipeline management platform for submission and monitoring of bioinformatics tasks in High Performance Computing (HPC) environments like local/cloud servers, clusters and grids. All the required tools, data and scripts are downloaded and installed in a single step. Researchers with diverse backgrounds and expertise have tested MOLGENIS-impute on different locations and imputed over 30,000 samples so far using the 1,000 Genomes Project and new Genome of the Netherlands data as the imputation reference. The tests have been performed on PBS/SGE clusters, cloud VMs and in a grid HPC environment. CONCLUSIONS: MOLGENIS-impute gives priority to the ease of setting up, configuring and running an imputation. It has minimal dependencies and wraps the pipeline in a simple command line interface, without sacrificing flexibility to adapt or limiting the options of underlying imputation tools. It does not require knowledge of a workflow system or programming, and is targeted at researchers who just want to apply best practices in imputation via simple commands. It is built on the MOLGENIS compute workflow framework to enable customization with additional computational steps or it can be included in other bioinformatics pipelines. It is available as open source from: https://github.com/molgenis/molgenis-imputation. PMID- 26286715 TI - Prevalence of genetic variants of keratins 8 and 18 in patients with drug-induced liver injury. AB - BACKGROUND: Keratin 8 and 18 (K8/K18) cytoskeletal proteins protect hepatocytes from undergoing apoptosis and their mutations predispose to adverse outcomes in acute liver failure (ALF). All known K8/K18 variants occur at relatively non conserved residues and do not cause keratin cytoskeleton reorganization, whereas epidermal keratin-conserved residue mutations disrupt the keratin cytoskeleton and cause severe skin disease. The aim of our study was to identify keratin variants in idiosyncratic drug-induced liver injury (DILI). METHODS: Genomic DNA was isolated from 800 patients enrolled in an ongoing US multicenter study, with DILI attributed to a wide range of drugs. Specific K8/K18 exonic regions were PCR amplified and screened by denaturing HPLC followed by DNA sequencing. The functional impact of keratin variants was assessed using cell transfection and immune staining. RESULTS: Heterozygous and compound amino acid-altering K8/K18 variants were identified in 86 DILI patients and non-coding variants in 15 subjects. Five novel amino acid-altering (K8 Lys393Arg, K8 Ala351Val, K8 Ala358Val, K8 Ile346Val, K18 Asp89His) and two non-coding variants were observed. Several variants segregated with specific ethnic backgrounds but were found at similar frequencies in DILI subjects and ethnically matched population controls. Notably, variants in highly conserved residues of K8 Lys393Arg (ezetimibe/simvastatin-related) and K18 Asp89His (isoniazid-related) were found in patients with fatal DILI. These novel variants also led to keratin network disruption in transfected cells. CONCLUSIONS: Novel K8/K18 cytoskeleton disrupting variants were identified in two patients and segregated with fatal DILI. Other non-cytoskeleton-disrupting keratin variants did not preferentially associate with DILI. PMID- 26286717 TI - Second-Site Mutagenesis of a Hypomorphic argonaute1 Allele Identifies SUPERKILLER3 as an Endogenous Suppressor of Transgene Posttranscriptional Gene Silencing. AB - Second-site mutagenesis was performed on the argonaute1-33 (ago1-33) hypomorphic mutant, which exhibits reduced sense transgene posttranscriptional gene silencing (S-PTGS). Mutations in FIERY1, a positive regulator of the cytoplasmic 5'-to-3' EXORIBONUCLEASE4 (XRN4), and in SUPERKILLER3 (SKI3), a member of the SKI complex that threads RNAs directly to the 3'-to-5' exoribonuclease of the cytoplasmic exosome, compensated AGO1 partial deficiency and restored S-PTGS with 100% efficiency. Moreover, xrn4 and ski3 single mutations provoked the entry of nonsilenced transgenes into S-PTGS and enhanced S-PTGS on partially silenced transgenes, indicating that cytoplasmic 5'-to-3' and 3'-to-5' RNA degradation generally counteract S-PTGS, likely by reducing the amount of transgene aberrant RNAs that are used by the S-PTGS pathway to build up small interfering RNAs that guide transgene RNA cleavage by AGO1. Constructs generating improperly terminated transgene messenger RNAs (mRNAs) were not more sensitive to ski3 or xrn4 than regular constructs, suggesting that improperly terminated transgene mRNAs not only are degraded from both the 3' end but also from the 5' end, likely after decapping. The facts that impairment of either 5'-to-3' or 3'-to-5' RNA degradation is sufficient to provoke the entry of transgene RNA into the S-PTGS pathway, whereas simultaneous impairment of both pathways is necessary to provoke the entry of endogenous mRNA into the S-PTGS pathway, suggest poor RNA quality upon the transcription of transgenes integrated at random genomic locations. PMID- 26286718 TI - Convergent Evolution of Endosymbiont Differentiation in Dalbergioid and Inverted Repeat-Lacking Clade Legumes Mediated by Nodule-Specific Cysteine-Rich Peptides. AB - Nutritional symbiotic interactions require the housing of large numbers of microbial symbionts, which produce essential compounds for the growth of the host. In the legume-rhizobium nitrogen-fixing symbiosis, thousands of rhizobium microsymbionts, called bacteroids, are confined intracellularly within highly specialized symbiotic host cells. In Inverted Repeat-Lacking Clade (IRLC) legumes such as Medicago spp., the bacteroids are kept under control by an arsenal of nodule-specific cysteine-rich (NCR) peptides, which induce the bacteria in an irreversible, strongly elongated, and polyploid state. Here, we show that in Aeschynomene spp. legumes belonging to the more ancient Dalbergioid lineage, bacteroids are elongated or spherical depending on the Aeschynomene spp. and that these bacteroids are terminally differentiated and polyploid, similar to bacteroids in IRLC legumes. Transcriptome, in situ hybridization, and proteome analyses demonstrated that the symbiotic cells in the Aeschynomene spp. nodules produce a large diversity of NCR-like peptides, which are transported to the bacteroids. Blocking NCR transport by RNA interference-mediated inactivation of the secretory pathway inhibits bacteroid differentiation. Together, our results support the view that bacteroid differentiation in the Dalbergioid clade, which likely evolved independently from the bacteroid differentiation in the IRLC clade, is based on very similar mechanisms used by IRLC legumes. PMID- 26286719 TI - A convex formulation for joint RNA isoform detection and quantification from multiple RNA-seq samples. AB - BACKGROUND: Detecting and quantifying isoforms from RNA-seq data is an important but challenging task. The problem is often ill-posed, particularly at low coverage. One promising direction is to exploit several samples simultaneously. RESULTS: We propose a new method for solving the isoform deconvolution problem jointly across several samples. We formulate a convex optimization problem that allows to share information between samples and that we solve efficiently. We demonstrate the benefits of combining several samples on simulated and real data, and show that our approach outperforms pooling strategies and methods based on integer programming. CONCLUSION: Our convex formulation to jointly detect and quantify isoforms from RNA-seq data of multiple related samples is a computationally efficient approach to leverage the hypotheses that some isoforms are likely to be present in several samples. The software and source code are available at http://cbio.ensmp.fr/flipflop. PMID- 26286720 TI - Assessment of genetic diversity in Ethiopian field pea (Pisum sativum L.) accessions with newly developed EST-SSR markers. AB - BACKGROUND: Field pea (Pisum sativum L.) is among the prominent crops in the world as food and feed. There are relatively few simple sequence repeat (SSR) markers developed from expressed sequence tags (ESTs) in P. sativum. RESULTS: In the present study, 15 new EST-SSR markers were developed from publicly available ESTs. These markers have successfully amplified their target loci across seven Pisum sativum subsp. sativum accessions. Eleven (73%) of these SSRs were trinucleotide repeats, two (13%) dinucleotide and two (13%) were hexanucleotide repeats. Across-taxa transferability of these new markers was also tested on other subspecies of Pisum as well as on P. fulvum, Vicia faba and Lens culinaris. In Pisum sativum subsp. sativum, 13 of the 15 markers were polymorphic and 12 of them subsequently used for genetic diversity analysis. Forty six accessions, of which 43 were from Ethiopia, were subjected to genetic diversity analysis using these newly developed markers. All accessions were represented by 12 individuals except two (NGB103816 and 237508) that were represented by 9 and 11 individuals, respectively. A total of 37 alleles were detected across all accessions. PS10 was the most polymorphic locus with six alleles, and the average number of alleles per locus over the 12 polymorphic loci was 3.1. Several rare and private alleles were also revealed. The most distinct accession (32048) had private alleles at three loci with 100% frequency. CONCLUSION: These newly developed EST-SSR primer pairs successfully amplified expected loci in P. sativum subsp. sativum as well as in other subspecies of the genus Pisum and related genera. High levels of genetic variation were detected in field pea accessions from Ethiopia using these markers. This result implies the potential of the Ethiopian field pea gene pool for improvement of field peas in various desirable traits. In addition, these markers could be a valuable asset in resolving the inconsistency in the taxonomic status of the different subspecies of genus Pisum as well as for characterization of field pea accessions in different gene banks around the world for breeding and conservation purposes. PMID- 26286723 TI - High levels of indium exposure relate to progressive emphysematous changes: a 9 year longitudinal surveillance of indium workers. AB - BACKGROUND: During the last decade it has been clarified that the inhalation of indium compounds can evoke alveolar proteinosis, cholesterol granuloma, pulmonary fibrosis and emphysema. In this study, we aimed to elucidate the characteristics and time course of pulmonary disorders among indium workers using comprehensive pulmonary examinations at an indium-processing factory. METHODS: Data for 84 male workers who underwent the examinations for nine consecutive years from 2002 to 2010 were analysed regarding their symptoms, serum indium concentration (sIn), serum markers of interstitial pneumonia, pulmonary function test parameters and high-resolution CT (HRCT) findings of the lungs. RESULTS: In association with improvements in the work environment and work practice, the sIn levels decreased with significant reductions in the KL-6 and surfactant protein D (SP-D) levels. Regarding the HRCT findings, the interstitial lesions regressed partially, whereas emphysematous lesions increased progressively in the workers with high sIn values. FEV1/FVC decreased with the years and the rate of decrease was significantly greater in those with high sIn. The biological half-life of sIn was estimated to be 8.09 years. CONCLUSIONS: The present findings suggest that the sIn, SP-D, KL-6 levels and radiological interstitial changes can be reduced in indium workers by alleviating exposure to indium, whereas emphysematous lesions can progress among those with a history of heavy exposure. PMID- 26286721 TI - Sphingosine-1-phosphate lyase is an endogenous suppressor of pulmonary fibrosis: role of S1P signalling and autophagy. AB - INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is characterised by accumulation of fibroblasts and myofibroblasts and deposition of extracellular matrix proteins. Sphingosine-1-phosphate (S1P) signalling plays a critical role in pulmonary fibrosis. METHODS: S1P lyase (S1PL) expression in peripheral blood mononuclear cells (PBMCs) was correlated with pulmonary functions and overall survival; used a murine model to check the role of S1PL on the fibrogenesis and a cell culture system to study the effect of S1PL expression on transforming growth factor (TGF)-beta- and S1P-induced fibroblast differentiation. RESULTS: S1PL expression was upregulated in fibrotic lung tissues and primary lung fibroblasts isolated from patients with IPF and bleomycin-challenged mice. TGF-beta increased the expression of S1PL in human lung fibroblasts via activation and binding of Smad3 transcription factor to Sgpl1 promoter. Overexpression of S1PL attenuated TGF-beta-induced and S1P-induced differentiation of human lung fibroblasts through regulation of the expression of LC3 and beclin 1. Knockdown of S1PL (Sgpl1(+/-)) in mice augmented bleomycin-induced pulmonary fibrosis, and patients with IPF reduced Sgpl1 mRNA expression in PBMCs exhibited higher severity of fibrosis and lower survival rate. CONCLUSION: These studies suggest that S1PL is a novel endogenous suppressor of pulmonary fibrosis in human IPF and animal models. PMID- 26286722 TI - Pulmonary macrophages: key players in the innate defence of the airways. AB - Macrophages are the most numerous immune-cells present in the lung environment under homoeostatic conditions and are ideally positioned to dictate the innate defence of the airways. Pulmonary macrophage populations are heterogeneous and demonstrate remarkable plasticity, owing to variations in origin, tissue residency and environmental influences. Lung macrophage diversity facilitates considerable specialisation, aids efficient responses to environmental signals and allows rapid alterations in phenotype and physiology in response to a plethora of cytokines and microbial signals. This review describes pulmonary macrophage origins, phenotypes, roles in diseases of the airways and implications for the treatment of respiratory disease. PMID- 26286724 TI - "From me to HIV": a case study of the community experience of donor transition of health programs. AB - BACKGROUND: Avahan, a large-scale HIV prevention program in India, transitioned over 130 intervention sites from donor funding and management to government ownership in three rounds. This paper examines the transition experience from the perspective of the communities targeted by these interventions. METHODS: Fifteen qualitative longitudinal case studies were conducted across all three rounds of transition, including 83 in-depth interviews and 45 focus group discussions. Data collection took place between 2010 and 2013 in four states: Andhra Pradesh, Karnataka, Maharashtra and Tamil Nadu. RESULTS: We find that communication about transition was difficult at first but improved over time, while issues related to employment of peer educators were challenging throughout the transition. Clinical services were shifted to government providers resulting in mixed experiences depending on the population being targeted. Lastly, the loss of activities aimed at community ownership and mobilization negatively affected the beneficiaries' view of transition. CONCLUSIONS: While some programmatic changes resulted in improvements, additional opportunity costs for beneficiaries may pose barriers to accessing HIV prevention services. Communicating and engaging community stakeholders early on in future such transitions may mitigate negative feelings and lead to more constructive relationships and dialogue. PMID- 26286726 TI - Malformations of the Left Ventricle: What Comes First: Form or Function? PMID- 26286725 TI - MicroRNA-101 is a potential prognostic indicator of laryngeal squamous cell carcinoma and modulates CDK8. AB - BACKGROUND: Various microRNAs (miRNAs) negatively modulate genes that are involved in cellular proliferation, differentiation, invasion, and apoptosis. In many types of cancer, the expression profiles of these miRNAs are altered. Recently, miR-101 was identified as a tumour suppressor and was found to be expressed at low levels in various types of tumours, including prostate, breast, endometrium, and bladder cancers. However, the function(s) of miR-101 in laryngeal carcinoma remain unknown. METHODS: The expression levels of miR-101 in laryngeal squamous cell carcinoma (LSCC) tissues and cells were detected by qPCR. Cell proliferation, migration, cell cycle, and apoptosis assay were applied to assess the function(s) of miR-101 in vitro. Nude mice subcutaneous tumour model was used to perform in vivo study. Moreover, we identified Cyclin-dependent kinase 8 (CDK8) as the target of miR-101 by a luciferase assay. The possible downstream effectors of CDK8 were investigated in Wnt/beta-catenin signaling pathway. Changes of CDK8, beta-catenin, and cyclin D1 protein levels were analyzed by western blotting and immunohistochemical staining. The prognostic effect of miR-101 was evaluated using the Kaplan-Meier method. RESULTS: Expression of miR-101 was down-regulated in the LSCC tissues compared with the adjacent normal tissues. Furthermore, downregulation of miR-101 correlated with T3-4 tumour grade, lymph node metastasis, and an advanced clinical stage in the LSCC patients examined (P < 0.05). The low level of miR-101 expression was associated with poor prognosis (P < 0.05). CDK8 was identified as the target gene of miR-101 by luciferase reporter assay. Moreover, we showed that up-regulation of miR-101 expression suppressed humen LSCC Hep-2 cells proliferation and migration, and induced cell-cycle arrest. Increased expression of miR-101 induced cells apoptosis both in vitro and in vivo. Correspondingly, exogenous expression of miR-101 significantly reduced the growth of tumour in a LSCC xenograft model. Furthermore, the miR-101 level was inversely correlated with levels of CDK8, beta catenin, and cyclin D1 in western blotting assay and immunohistochemical staining assay. CONCLUSIONS: These results indicate that miR-101 is a potent tumour repressor that directly represses CDK8 expression. Thus, detection and targeting of miR-101 may represent a novel diagnostic and therapeutic strategy for LSCC patients. PMID- 26286727 TI - Blood Pressure Genetics Just Don't Add Up. PMID- 26286728 TI - Giant Heart of Classical Infantile-Onset Pompe Disease With Mirror Image Dextrocardia. PMID- 26286730 TI - Design Issues in Randomized Clinical Trials of Maintenance Therapies. AB - A potential therapeutic strategy for patients who respond (or have stable disease) on a fixed-duration induction therapy is to receive maintenance therapy, typically given for a prolonged period of time. To enable patients and clinicians to make informed treatment decisions, the designs of phase III randomized clinical trials (RCTs) assessing maintenance strategies need to be such that their results will provide clear assessment of the relevant risks and benefits of these strategies. We review the key aspects of maintenance RCT designs. Important design considerations include choice of first-line and second-line therapies, minimizing between-arm differences in follow-up schedules, and choice of the primary endpoint. In order to change clinical practice, RCTs should be designed to accurately isolate and quantify the clinical benefit of maintenance as compared with the standard approach of fixed-duration induction followed by the second-line treatment at progression. To accomplish this, RCTs need to utilize an overall survival (or quality of life) endpoint or, in settings where this is not feasible, endpoints that incorporate the effects of the subsequent line of therapy (eg, time from randomization to second progression or death). Toxicity and symptom information over both the study treatment (maintenance) and the second-line treatment should also be collected and reported. PMID- 26286729 TI - Repression of Esophageal Neoplasia and Inflammatory Signaling by Anti-miR-31 Delivery In Vivo. AB - BACKGROUND: Overexpression of microRNA-31 (miR-31) is implicated in the pathogenesis of esophageal squamous cell carcinoma (ESCC), a deadly disease associated with dietary zinc deficiency. Using a rat model that recapitulates features of human ESCC, the mechanism whereby Zn regulates miR-31 expression to promote ESCC is examined. METHODS: To inhibit in vivo esophageal miR-31 overexpression in Zn-deficient rats (n = 12-20 per group), locked nucleic acid modified anti-miR-31 oligonucleotides were administered over five weeks. miR-31 expression was determined by northern blotting, quantitative polymerase chain reaction, and in situ hybridization. Physiological miR-31 targets were identified by microarray analysis and verified by luciferase reporter assay. Cellular proliferation, apoptosis, and expression of inflammation genes were determined by immunoblotting, caspase assays, and immunohistochemistry. The miR-31 promoter in Zn-deficient esophagus was identified by ChIP-seq using an antibody for histone mark H3K4me3. Data were analyzed with t test and analysis of variance. All statistical tests were two-sided. RESULTS: In vivo, anti-miR-31 reduced miR-31 overexpression (P = .002) and suppressed the esophageal preneoplasia in Zn deficient rats. At the same time, the miR-31 target Stk40 was derepressed, thereby inhibiting the STK40-NF-kappaBeta-controlled inflammatory pathway, with resultant decreased cellular proliferation and activated apoptosis (caspase 3/7 activities, fold change = 10.7, P = .005). This same connection between miR-31 overexpression and STK40/NF-kappaBeta expression was also documented in human ESCC cell lines. In Zn-deficient esophagus, the miR-31 promoter region and NF kappaBeta binding site were activated. Zn replenishment restored the regulation of this genomic region and a normal esophageal phenotype. CONCLUSIONS: The data define the in vivo signaling pathway underlying interaction of Zn deficiency and miR-31 overexpression in esophageal neoplasia and provide a mechanistic rationale for miR-31 as a therapeutic target for ESCC. PMID- 26286731 TI - The Role of Multidrug Resistance Efflux Pumps in Cancer: Revisiting a JNCI Publication Exploring Expression of the MDR1 (P-glycoprotein) Gene. PMID- 26286733 TI - The Plasminogen System and Transforming Growth Factor-beta in Subjects With Obstructive Sleep Apnea Syndrome: Effects of CPAP Treatment. AB - BACKGROUND: Obstructive sleep apnea syndrome (OSAS) has emerged as a risk factor for cardiovascular disease. A prothrombotic state may affect coagulation and participate in the atherosclerotic process in subjects with OSAS. These alterations in coagulation seem to involve the plasminogen activation system. We evaluated the imbalances of the plasminogen activation system related to OSAS, and we assessed the effects of CPAP on the plasminogen activation system. METHODS: Thirty-nine subjects were submitted to a home-based cardiorespiratory sleep study, and 14 healthy subjects (apnea-hypopnea index < 5) were used as controls. Serum levels of urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), and active transforming growth factor-beta (TGF-beta) were measured. These molecules were reassessed in only 17 of the subjects after 1 month of CPAP. RESULTS: PAI-1 and tPA were significantly higher in the subjects with OSAS compared with the controls, whereas TGF-beta and uPA levels were lower. PAI-1 showed a significant positive correlation with the apnea-hypopnea index, percentage of time spent at O2 saturation < 90%, and oxygen desaturation index, whereas TGF-beta was inversely related to all 3 of these parameters. After the CPAP therapy, PAI-1 significantly decreased, whereas TGF-beta showed a significant increase, although the values did not reach those of the controls. uPA and tPA did not show significant differences after the treatment. CONCLUSIONS: Our results suggest an imbalance of fibrinolysis related to OSAS and an improvement of the prothrombotic state after the CPAP treatment. PMID- 26286732 TI - Sphingosine 1-Phosphate Receptor 3-Deficient Dendritic Cells Modulate Splenic Responses to Ischemia-Reperfusion Injury. AB - The plasticity of dendritic cells (DCs) permits phenotypic modulation ex vivo by gene expression or pharmacologic agents, and these modified DCs can exert therapeutic immunosuppressive effects in vivo through direct interactions with T cells, either inducing T regulatory cells (T(REG)s) or causing anergy. Sphingosine 1-phosphate (S1P) is a sphingolipid and the natural ligand for five G protein-coupled receptors (S1P1, S1P2, S1P3, S1P4, and S1P5), and S1PR agonists reduce kidney ischemia-reperfusion injury (IRI) in mice. S1pr3(-/-)mice are protected from kidney IRI, because DCs do not mature. We tested the therapeutic advantage of S1pr3(-/-) bone marrow-derived dendritic cell (BMDC) transfers in kidney IRI. IRI produced a rise in plasma creatinine (PCr) levels in mice receiving no cells (NCs) and mice pretreated with wild-type (WT) BMDCs. However, S1pr3(-/-) BMDC-pretreated mice were protected from kidney IRI. S1pr3(-/-) BMDC pretreated mice had significantly higher numbers of splenic T(REG)s compared with NC and WT BMDC-pretreated mice. S1pr3(-/-) BMDCs did not attenuate IRI in splenectomized, Rag-1(-/-), or CD11c(+) DC-depleted mice. Additionally, S1pr3(-/ ) BMDC-dependent protection required CD169(+)marginal zone macrophages and the macrophage-derived chemokine CCL22 to increase splenic CD4(+)Foxp3(+) T(REG)s. Pretreatment with S1pr3(-/-) BMDCs also induced T(REG)-dependent protection against IRI in an allogeneic mouse model. In summary, adoptively transferred S1pr3(-/-) BMDCs prevent kidney IRI through interactions within the spleen and expansion of splenic CD4(+)Foxp3(+) T(REG)s. We conclude that genetically induced deficiency of S1pr3 in allogenic BMDCs could serve as a therapeutic approach to prevent IRI-induced AKI. PMID- 26286734 TI - Accuracy of the Electronic Health Record: Patient Height. AB - BACKGROUND: Protective lung ventilation requires calculating predicted body weight (BW) from height. Thus, inaccuracy of height data in the electronic health record (EHR) is a risk factor for ventilator-induced lung injury. Charted height data often have uncertain accuracy. Study purposes were (1) to evaluate the difference between patient height charted in the EHR and predicted height (PH) from ulnar length and (2) to determine how the height data source affects predicted BW and the resulting values for protective tidal volume (V(T)). METHODS: Subject height data from the EHR were collected from several ICUs. Simultaneous ulnar data were collected by measuring ulnar length (cm): male PH (cm) = 79.2 +/- 3.60 * ulnar length; female PH = 95.6 +/- 2.77 * ulnar length. For each subject, BW (kg) was calculated from height charted in EHR and from predicted height: male BW = 50 +/- 0.91 * (height - 152.4); female BW = 45.5 +/- 0.91 * (height - 152.4). Then V(T) was calculated as 8 mL/kg BW. Bland-Altman analysis of height and V(T) differences (charted - predicted) determined the limits of agreement. RESULTS: For white males (n = 27) the mean (SD) height from EHR was 177 (7.5); predicted height was 178 (6.9). The limits of agreement for height in males were -18.5 and 17.8 cm. The limits of agreement for females were 23.1 and 21.3 cm. The limits of agreement for V(T) in males were -1.8 and 1.8 mL/kg. The limits of agreement for V(T) in females were -3.0 and 2.9 mL/kg. CONCLUSIONS: For overall populations, mean height calculated from values charted in the EHR is similar to that estimated from ulnar length. However, for individuals, differences in height between the 2 sources can be large, leading to large differences in predicted BW and resultant V(T) set in terms of mL/kg. PMID- 26286735 TI - Electromyographic Manifestations of Fatigue Correlate With Pulmonary Function, 6 Minute Walk Test, and Time to Exhaustion in COPD. AB - BACKGROUND: The aim of this study was to investigate whether electromyographic manifestations of fatigue and exercise tolerance were related to stage of disease in men with a COPD diagnosis. METHODS: Fourteen men with COPD with a diagnosis of mild to severe air flow obstruction were involved in 2 separate testing sessions. The first one consisted of a pulmonary function (FEV1 and FEV1/FVC) and an exercise tolerance assessment using the 6-min walk test. During the second session, a multichannel surface electromyography was recorded from vastus medialis and vastus lateralis muscles during an isometric knee extension at 70% of maximum voluntary contraction. The slope of muscle fiber conduction velocity during the contraction was calculated as the index of fatigue. RESULTS: Conduction velocity slope significantly correlated with FEV1 (vastus medialis: r = 0.86, P < .001; vastus lateralis: r = 0.68, P = .01), FEV1/FVC (vastus medialis: r = 0.70, P = .006), and 6-min walk test (vastus medialis: r = 0.72, P = .005; vastus lateralis: r = 0.80, P = .001). CONCLUSIONS: The electromyographic manifestations of fatigue during sustained quadriceps contraction significantly correlated with disease severity and exercise tolerance in moderate to severe COPD. PMID- 26286736 TI - Albuterol Delivery via Facial and Tracheostomy Route in a Model of a Spontaneously Breathing Child. AB - BACKGROUND: Some pediatric patients receiving therapeutic aerosols undergo tracheostomy, and others who are tracheostomized continue requiring inhaled therapies upon decannulation. It is unknown whether a dose adjustment is required. Different devices are available for facial and tracheostomy delivery, and in some instances, the assisted technique is used. We hypothesized that the change from face mask to tracheostomy would result in a decrease in the lung dose. METHODS: A breathing simulator connected in series to a filter holder and an anatomically correct head model of a child was used. The drug captured in the filter was termed the lung dose. Breathing patterns with tidal volumes of 50, 155, and 300 mL were tested. Albuterol hydrofluoroalkane (pressurized metered dose inhaler [pMDI]) with an AeroChamber Mini (face and 4.5-mm tracheostomy), AeroTrach (4.5-mm tracheostomy), and AeroChamber (face) and albuterol (2.5 mg/3 mL) with a continuous output nebulizer (face and 4.5-mm tracheostomy) were tested. Masks were used for facial delivery. Four units of each device were tested. Particle size of the pMDI was measured by cascade impaction. Albuterol concentration was determined via spectrophotometry (276 nm). RESULTS: Switching from facial to tracheostomy delivery increased lung dose with nebulizer (all breathing patterns). When a pMDI was used, lung dose was unchanged or increased for the 50- and 155-mL and decreased for the 300-mL breathing pattern. The use of the assisted technique increased lung dose only during nebulization with the 300 mL breathing pattern. The particle size of the pMDI decreased by 19-23% when traveling through the tracheostomy tube, which retained < 4% and < 26% of the nominal dose of a nebulizer and pMDI, respectively. CONCLUSIONS: The effect of changing the delivery route from face to tracheostomy was variable and depended on the delivery device and the breathing pattern. There is no advantage of using the assisted technique to enhance aerosol delivery. PMID- 26286737 TI - Predictive Model of Hospital Admission for COPD Exacerbation. AB - BACKGROUND: The objective of this work was to determine predictive factors of hospital admission for exacerbation during primary care visits in patients with COPD. METHODS: A retrospective cohort study was undertaken to assess risk of hospital admission for COPD exacerbation in primary care patients from November 1, 2010 to October 31, 2013. Data sources were primary care electronic medical records and the hospital discharge minimum data set. A total of 2,501 subjects >40 y of age with a spirometry-based COPD diagnosis were included and followed up for 3 y. The dependent variable was hospital admission for exacerbation; independent variables were: clinical parameters, spirometry results, and severity of disease (according to Global Initiative for Chronic Obstructive Lung Disease criteria). The association of these variables with hospital admission was analyzed with the adjusted odds ratio using a logistic regression model. RESULTS: Mean age of subjects at the beginning of the study was 68.4 y (SD = 11.6), and 75% were men. Severity was mild in 50.8% of subjects, moderate in 35.3%, severe in 9.4%, and very severe in 4.4%. After 3 y, 32.5% of subjects had been admitted for exacerbation. Predictive values for hospital admission were: age, sex, previous exacerbations, number of visits to the primary care center, comorbidities, smoking, severity (Global Initiative for Chronic Obstructive Lung Disease), and influenza immunization. The area under the receiving operator characteristic curve was 0.72. CONCLUSIONS: This model can identify patients at high risk of hospital admission for COPD exacerbation in our setting. Further studies are needed to validate the model in different populations and settings. PMID- 26286738 TI - Relapse Rate and Factors Related to Relapse in a 1-Year Follow-Up of Subjects Participating in a Smoking Cessation Program. AB - BACKGROUND: The most important and difficult task when it comes to reducing tobacco-related morbidity and mortality is to convince smokers to quit and to maintain their abstinence. This study aimed to determine the smoking relapse rate and factors related to relapse in subjects who participated in a smoking cessation program and completed a 1-y follow-up in our center. METHODS: The study included 550 subjects who applied to a smoking cessation clinic from June 1, 2011 to December 31, 2011 and completed the 1-y follow-up. RESULTS: After 1 y, 282 (51.4%) subjects had relapsed, 132 (24%) had quit smoking, and 135 (24.6%) could not be contacted. The mean age +/- SD was 41.5 +/- 10.8 y, and 52.5% were male. There was no difference between non-relapsed and relapsed subjects with regard to age, sex, average smoking duration and daily number of cigarettes, reason to quit, education level, presence of symptoms and concomitant diseases, Fagerstrom nicotine dependence score, Beck depression score, and frequency of pharmacotherapy administration. In the relapsed group, the age began smoking was younger (P = .05), and the longest prior duration of abstinence was shorter (P = .04). The average number of support contacts was found to be significantly higher in the non-relapsed subjects (P < .001). Logistic regression analysis revealed alcohol intake to be a factor influencing relapse (odds ratio: 2.11, 95% CI: 1.13 3.93, P = .02), as was the number of support contacts (odds ratio: 2.06, 95% CI: 1.59-2.65, P < .001). The presence of drug adverse effects was close to being significant (odds ratio: 1.96, 95% CI: 0.93-4.10, P = .07). CONCLUSION: The relapse rate in a 1-y period was 51.4%. Similar to previous studies, alcohol intake presented a relapse risk. In subjects receiving drug treatment, planning support meetings more frequently and paying attention to adverse effects may increase the success of smoking cessation. PMID- 26286739 TI - Chronic Occlusion of the Superior Vena Cava Resulting in Cyanosis in an Adult: Unusual Case Highlighting the Value of Collaboration Between Adult and Congenital Cardiology Services. PMID- 26286740 TI - Effect of Clinical Trial Experience on Transcatheter Aortic Valve Replacement Outcomes. AB - BACKGROUND: Transcatheter aortic valve replacement (TAVR) was approved by the Food and Drug Administration (FDA) in November 2011 after a collaborative technology development process involving professional medical societies, the medical device industry, and the FDA. After FDA approval, TAVR was adopted by numerous hospitals that had not participated in TAVR clinical trials. It is uncertain if outcomes at these hospitals were comparable with those at clinical trial hospitals. METHODS AND RESULTS: All patients with Medicare physician claims for TAVR between January 1, 2011, and November 30, 2012, were identified, and postoperative mortality was assessed using Medicare enrollment data. Risk adjusted mortality was calculated via a multivariable model that adjusted for demographics and comorbidities. We identified 5009 patients who underwent TAVR, with 3617 TAVRs performed at 68 hospitals that had participated in clinical trials and 1392 TAVRs performed at 140 nontrial hospitals. The preoperative characteristics of patients at trial versus nontrial hospitals were similar. There were no significant differences in risk-adjusted 30-day mortality (5.9% versus 5.6%, odds ratio, 0.88; 95% confidence interval, 0.66-1.15; P=0.34) or 180 day mortality (16.5% versus 15.8%, odds ratio, 0.99; 95% confidence interval, 0.75-1.3; P=0.94). CONCLUSIONS: Patients undergoing TAVR at nontrial hospitals had comparable clinical outcomes to patients undergoing TAVR at clinical trial hospitals. This finding contrasts with several other cardiovascular devices and procedures for which higher mortality was observed at hospitals that did not participate in clinical trials. The unique policy and regulatory environment governing TAVR adoption by hospitals may have contributed to better outcomes during the technology diffusion process. PMID- 26286743 TI - The fast-track ultrasound clinic for early diagnosis of giant cell arteritis significantly reduces permanent visual impairment: towards a more effective strategy to improve clinical outcome in giant cell arteritis? AB - OBJECTIVE: Permanent visual impairment has been reported to occur in up to 19% of GCA patients. The aim of this study was to examine whether implementation of a fast-track approach could reduce the rate of permanent visual impairment and inpatient days of care in GCA patients. METHODS: A fast-track outpatient GCA clinic (FTC) was implemented in the Department of Rheumatology, Hospital of Southern Norway Trust Kristiansand, Norway in 2012. The patients included in this study were subsequently recruited between March 2010 and October 2014. Routine clinical and laboratory data and number of inpatient days of care were collected. RESULTS: During the observation period, 75 patients were diagnosed with GCA. Among the 75 GCA patients, 32 were evaluated conventionally and 43 in the FTC. In the conventionally approached group, six patients suffered from permanent visual impairment, while in the FTC group only one patient suffered from permanent visual impairment. The relative risk of permanent visual impairment in the GCA patients examined in the FTC was 88% lower compared with the conventionally evaluated group (relative risk 0.12, 95% CI: 0.01, 0.97, P = 0.01). The mean difference in inpatient days of care between patients evaluated conventionally and patients evaluated in the FTC was 3 days (3.6 vs 0.6 days, P < 0.0005). CONCLUSION: The implementation of the FTC in GCA care appears to significantly reduce the risk of permanent visual impairment and is more cost effective by reducing the need for inpatient care. PMID- 26286744 TI - Severe adult dermatomyositis with unusual calcinosis. PMID- 26286745 TI - The use of duplex-specific nuclease in ribosome profiling and a user-friendly software package for Ribo-seq data analysis. AB - Ribosome profiling is a technique that permits genome-wide, quantitative analysis of translation and has found broad application in recent years. Here we describe a modified profiling protocol and software package designed to benefit more broadly the translation community in terms of simplicity and utility. The protocol, applicable to diverse organisms, including organelles, is based largely on previously published profiling methodologies, but uses duplex-specific nuclease (DSN) as a convenient, species-independent way to reduce rRNA contamination. We show that DSN-based depletion compares favorably with other commonly used rRNA depletion strategies and introduces little bias. The profiling protocol typically produces high levels of triplet periodicity, facilitating the detection of coding sequences, including upstream, downstream, and overlapping open reading frames (ORFs) and an alternative ribosome conformation evident during termination of protein synthesis. In addition, we provide a software package that presents a set of methods for parsing ribosomal profiling data from multiple samples, aligning reads to coding sequences, inferring alternative ORFs, and plotting average and transcript-specific aspects of the data. Methods are also provided for extracting the data in a form suitable for differential analysis of translation and translational efficiency. PMID- 26286746 TI - eIF4AII is dispensable for miRNA-mediated gene silencing. AB - MicroRNAs (miRNAs) are short noncoding RNAs that regulate gene expression through partial complementary base-pairing to the 3' untranslated region (UTR) of target mRNAs. Inhibition of translation initiation has been identified as an early event of miRNA-mediated gene repression, but the underlying mechanistic details of this process are not well understood. Recently, eukaryotic initiation factor (eIF) 4AII was identified as a critical modulator of miRNA activity with depletion of this factor alleviating miRNA-mediated gene repression. Using the CRISPR/Cas9 editing system, we generated a novel cell line in which expression of eIF4AII was eliminated. The absence of eIF4AII does not affect cell viability, proliferation, or global mRNA translation. Importantly, we show that eIF4AII is dispensable for miRNA-mediated gene silencing. PMID- 26286747 TI - MicroRNA-542-3p Suppresses Tumor Cell Invasion via Targeting AKT Pathway in Human Astrocytoma. AB - The molecular mechanism underlying constitutive activation of AKT signaling, which plays essential roles in astrocytoma progression, is not fully characterized. Increasing numbers of studies have reported that microRNAs are involved in the malignant behavior of astrocytoma cells via directly targeting multiple oncogenes or tumor suppressors. Here, we found that microRNA (miR)-542 3p expression was decreased in glioblastoma cell lines and astrocytoma tissues, and reduced levels of miR-542-3p expression correlated with high histopathological grades and poor prognosis of astrocytoma patients. Exogenous miR-542-3p suppressed glioblastoma cell invasion through not only targeting AKT1 itself but also directly down-regulating its two important upstream regulators, namely, integrin-linked kinase and PIK3R1. Notably, overexpressing miR-542-3p decreased AKT1 phosphorylation and directly and indirectly repressed nuclear translocation and transactivation activity of beta-catenin to exert its anti invasive effect. Furthermore, the miR-542-3p expression level negatively correlated with AKT activity as well as levels of integrin-linked kinase and PIK3R1 in human astrocytoma specimens. These findings suggest that miR-542-3p acts as a negative regulator in astrocytoma progression and that miR-542-3p down regulation contributes to aberrant activation of AKT signaling, leaving open the possibility that miR-542-3p may be a potential therapeutic target for high grade astrocytoma. PMID- 26286748 TI - Alternative Activation Mechanisms of Protein Kinase B Trigger Distinct Downstream Signaling Responses. AB - Protein kinase B (PKB/Akt) is an important mediator of signals that control various cellular processes including cell survival, growth, proliferation, and metabolism. PKB promotes these processes by phosphorylating many cellular targets, which trigger distinct downstream signaling events. However, how PKB is able to selectively target its substrates to induce specific cellular functions remains elusive. Here we perform a systematic study to dissect mechanisms that regulate intrinsic kinase activity versus mechanisms that specifically regulate activity toward specific substrates. We demonstrate that activation loop phosphorylation and the C-terminal hydrophobic motif are essential for high PKB activity in general. On the other hand, we identify membrane targeting, which for decades has been regarded as an essential step in PKB activation, as a mechanism mainly affecting substrate selectivity. Further, we show that PKB activity in cells can be triggered independently of PI3K by initial hydrophobic motif phosphorylation, presumably through a mechanism analogous to other AGC kinases. Importantly, different modes of PKB activation result in phosphorylation of distinct downstream targets. Our data indicate that specific mechanisms have evolved for signaling nodes, like PKB, to select between various downstream events. Targeting such mechanisms selectively could facilitate the development of therapeutics that might limit toxic side effects. PMID- 26286749 TI - Dephosphorylation during bleach and regeneration of visual pigment in carp rod and cone membranes. AB - On absorption of light by vertebrate visual pigment, the chromophore, 11-cis retinal, is isomerized to all-trans retinal to activate the phototransduction cascade, which leads to a hyperpolarizing light response. Activated pigment is inactivated by phosphorylation on the protein moiety, opsin. Isomerized all-trans retinal is ultimately released from opsin, and the pigment is regenerated by binding to 11-cis retinal. In this pigment regeneration cycle, the phosphates incorporated should be removed in order that the pigment regains the capability of activating the phototransduction cascade. However, it is not clear yet how pigment dephosphorylation takes place in the regeneration cycle. First in this study, we tried to estimate the dephosphorylation activity in living carp rods and cones and found that the activity, which is present mainly in the cytoplasm in both rods and cones, is three times higher in cones than in rods. Second, we examined at which stage the dephosphorylation takes place; before or after the release of all-trans retinal, during pigment regeneration, or after pigment regeneration. For this purpose we prepared three types of phosphorylated substrates in purified carp rod and cone membranes: phosphorylated bleaching intermediate, phosphorylated opsin, and phosphorylated and regenerated pigment. We also examined the effect of pigment regeneration on the dephosphorylation. The results showed that the dephosphorylation does not show substrate preference in the regeneration cycle and suggested that the dephosphorylation takes place constantly. The results also suggest that, under bright light, some of the regenerated visual pigment remains phosphorylated to reduce the light sensitivity in cones. PMID- 26286750 TI - The capsule polymerase CslB of Neisseria meningitidis serogroup L catalyzes the synthesis of a complex trimeric repeating unit comprising glycosidic and phosphodiester linkages. AB - Neisseria meningitidis is a human pathogen causing bacterial meningitis and sepsis. The capsular polysaccharide surrounding N. meningitidis is a major virulence factor. The capsular polysaccharide consists of polyhexosamine phosphates in N. meningitidis serogroups A and X. The capsule polymerases (CPs) of these serogroups are members of the Stealth protein family comprising d-hexose 1-phosphate transferases from bacterial and protozoan pathogens. CslA, one of two putative CPs of the pathophysiologically less relevant N. meningitidis serogroup L, is one of the smallest known Stealth proteins and caught our attention for structure-function analyses. Because the N. meningitidis serogroup L capsule polymer consists of a trimeric repeating unit ([->3)-beta-d-GlcNAc-(1->3)-beta-d GlcNAc-(1->3)-alpha-d-GlcNAc-(1->OPO3->]n), we speculated that the two predicted CPs (CslA and CslB) work together in polymer production. Consequently, both enzymes were cloned, overexpressed, and purified as recombinant proteins. Contrary to our expectation, enzymatic testing identified CslB to be sufficient to catalyze the synthesis of the complex trimeric N. meningitidis serogroup L capsule polymer repeating unit. No polymerase activity was detected for CslA, although the enzyme facilitated the hydrolysis of UDP-GlcNAc. Bioinformatics analyses identified two glycosyltransferase (GT) domains in CslB. The N-terminal domain modeled with 100% confidence onto a number of GT-A folded proteins, whereas the C-terminal domain modeled with 100% confidence onto TagF, a GT-B folded teichoic acid polymerase from Staphylococcus epidermidis. Amino acid positions known to have critical catalytic functions in the template proteins were conserved in CslB, and their point mutation abolished enzyme activity. CslB represents an enzyme of so far unique complexity regarding both the catalyzed reaction and enzyme architecture. PMID- 26286751 TI - Site-directed Mutagenesis Shows the Significance of Interactions with Phospholipids and the G-protein OsYchF1 for the Physiological Functions of the Rice GTPase-activating Protein 1 (OsGAP1). AB - The C2 domain is one of the most diverse phospholipid-binding domains mediating cellular signaling. One group of C2-domain proteins are plant-specific and are characterized by their small sizes and simple structures. We have previously reported that a member of this group, OsGAP1, is able to alleviate salt stress and stimulate defense responses, and bind to both phospholipids and an unconventional G-protein, OsYchF1. Here we solved the crystal structure of OsGAP1 to a resolution of 1.63 A. Using site-directed mutagenesis, we successfully differentiated between the clusters of surface residues that are required for binding to phospholipids versus OsYchF1, which, in turn, is critical for its role in stimulating defense responses. On the other hand, the ability to alleviate salt stress by OsGAP1 is dependent only on its ability to bind OsYchF1 and is independent of its phospholipid-binding activity. PMID- 26286753 TI - Getting controls under control: the time is now for immunohistochemistry. AB - For several decades, immunohistochemistry (IHC), more specifically diagnostic IHC (dIHC), has been considered an art rather than a laboratory test. There was no clarity about what test performance characteristics are relevant to dIHC, test performance characteristics were not fully defined for dIHC and partly as a consequence of that, there were no standardised controls or reference standards. Herein, we discuss the role of standardisation of external controls for test performance characteristics and the role of standardised controls and reference standards for overall standardisation of IHC. PMID- 26286752 TI - The GH130 Family of Mannoside Phosphorylases Contains Glycoside Hydrolases That Target beta-1,2-Mannosidic Linkages in Candida Mannan. AB - The depolymerization of complex glycans is an important biological process that is of considerable interest to environmentally relevant industries. beta-Mannose is a major component of plant structural polysaccharides and eukaryotic N glycans. These linkages are primarily cleaved by glycoside hydrolases, although recently, a family of glycoside phosphorylases, GH130, have also been shown to target beta-1,2- and beta-1,4-mannosidic linkages. In these phosphorylases, bond cleavage was mediated by a single displacement reaction in which phosphate functions as the catalytic nucleophile. A cohort of GH130 enzymes, however, lack the conserved basic residues that bind the phosphate nucleophile, and it was proposed that these enzymes function as glycoside hydrolases. Here we show that two Bacteroides enzymes, BT3780 and BACOVA_03624, which lack the phosphate binding residues, are indeed beta-mannosidases that hydrolyze beta-1,2-mannosidic linkages through an inverting mechanism. Because the genes encoding these enzymes are located in genetic loci that orchestrate the depolymerization of yeast alpha mannans, it is likely that the two enzymes target the beta-1,2-mannose residues that cap the glycan produced by Candida albicans. The crystal structure of BT3780 in complex with mannose bound in the -1 and +1 subsites showed that a pair of glutamates, Glu(227) and Glu(268), hydrogen bond to O1 of alpha-mannose, and either of these residues may function as the catalytic base. The candidate catalytic acid and the other residues that interact with the active site mannose are conserved in both GH130 mannoside phosphorylases and beta-1,2-mannosidases. Functional phylogeny identified a conserved lysine, Lys(199) in BT3780, as a key specificity determinant for beta-1,2-mannosidic linkages. PMID- 26286754 TI - From water-in-oil to oil-in-water emulsions to optimize the production of fatty acids using ionic liquids in micellar systems. AB - Biocatalysis is nowadays considered as one of the most important tools in green chemistry. The elimination of multiple steps involved in some of the most complex chemical synthesis, reducing the amounts of wastes and hazards, thus increasing the reaction yields and decreasing the intrinsic costs, are the major advantages of biocatalysis. This work aims at improving the enzymatic hydrolysis of olive oil to produce valuable fatty acids through emulsion systems formed by long alkyl chain ionic liquids (ILs). The optimization of the emulsion and the best conditions to maximize the production of fatty acids were investigated. The stability of the emulsion was characterized considering the effect of several parameters, namely, the IL and its concentration and different water/olive oil volumetric ratios. ILs from the imidazolium and phosphonium families were evaluated. The results suggest that the ILs effect on the hydrolysis performance varies with the water concentration and the emulsion system formed, that is, water-in-oil or oil-in-water emulsion. Although at low water concentrations, the presence of ILs does not present any advantages for the hydrolysis reaction, at high water contents (in oil-in-water emulsions), the imidazolium-based IL acts as an enhancer of the lipase catalytic capacity, super-activating 1.8 times the enzyme, and consequently promoting the complete hydrolysis of the olive oil for the highest water contents [85% (v/v)]. PMID- 26286755 TI - Simultaneous Descemet's membrane endothelial keratoplasty and posterior iris-claw fixated intra ocular lens implantation (IOL) in management of aphakic bullous keratopathy. AB - To evaluate the efficacy of combined procedure of Descemet's membrane endothelial keratoplasty (DMEK) and posterior iris-claw-fixated intra ocular lens (IOL) implantation in the management of aphakic bullous keratopathy (ABK). Sankara eye centre, a tertiary eye care centre. A prospective case series analysis. A prospective study comprised ten eyes of ten patients who underwent DMEK and posterior iris-claw-fixated IOL. Mean follow-up period was 12-36 months. Pre operative and post-operative best corrected visual acuity (BCVA), endothelial cell density (ECD) and complications were noted. A total ten eyes of ten patients underwent DMEK. Out of ten patients BCVA improved from 1.00 to 1.60 LogMAR with mean and SD of 1.40 +/- 0.20 to +0.20-0.40 LogMAR with mean and SD of 0.30 +/- 0.07, with a significant p value of <0.001, Mean ECD of the donor tissue pre operatively was 2367 cells, whereas 24 months post-operatively it was reduced to 1798 cells. Mean reduction in ECD pre procedure and post procedure was 569 (24 %). Iris-fixated IOL appears to offer simplicity in implantation and may be combined with DMEK in ABK. This procedure provides a faster visual recovery than other endothelial keratoplasties with iris-fixated IOL. PMID- 26286758 TI - The field of fertility preservation comes of age. PMID- 26286756 TI - Effect on contrast sensitivity after clear, yellow and orange intraocular lens implantation. AB - The objective of this study is to evaluate contrast sensitivity function (CSF) after clear, yellow- and orange-tinted intraocular lens (IOL) implantation. This was a prospective randomized study of 98 patients with senile cataract for a period of 6 months from day 1 of August 2014 to day 31 of January 2015. After phacoemulsification, 33 patients were implanted with clear IOLs (AcrySof UV filtering IOL, SA60AT), 32 patients were implanted with yellow coloured IOLs (AcrySof Natural blue-light-attenuating and UV-filtering IOL, SN60AT with IMPRUV((r)) filter) and 33 patients were implanted with orange-tinted blue filtering IOLs (PC440Y Optech). After 1 month, monocular CSF was done under photopic (85 cd/m(2)) and mesopic (3 cd/m(2)) illumination condition with CSV 1000 test. The best corrected visual acuity (BCVA) after 1 month was 0.021 +/- 0.058 logMAR for clear lens, 0.022 +/- 0.059 logMAR for yellow lens and 0.019 +/- 0.065 logMAR for orange lens (p = 0.989). Uniocular average photopic contrast sensitivity was 1.36 +/- 0.19, 1.43 +/- 0.18 and 1.46 +/- 0.15 log units for clear lens, yellow lens and orange lens, respectively (statistically not significant; p = 0.076). Average mesopic contrast sensitivity was 1.02 +/- 0.21 log units for clear lens, 1.00 +/- 0.17 log units for yellow lens and 0.99 +/- 0.15 log units for orange lens (statistically not significant; p = 0.771). Yellow or orange coloured blue-filtering IOLs are comparable to clear IOLs in terms of photopic and mesopic contrast sensitivity. PMID- 26286757 TI - Central corneal thickness and intraocular pressure in premature infants. AB - To evaluate the central corneal thickness (CCT) and intraocular pressure (IOP) of premature infants and to document correlation of them with gestational age, chronological age, and birth weight of infants. Using a hand-held applanation tonometer and a portable pachymeter, IOP and CCT of 170 premature infants were measured just before initial retinopathy of prematurity screening examination and re-measured 4 weeks after the first visit. The CCT and IOP were positively correlated during the first (r = 0.616, p < 0.001) and second (r = 0.564, p < 0.001) visits. The mean CCT at first and second visits were 568.1 +/- 22.1 (527 628) and 561.6 +/- 21.4 (520-619) um, consecutively (p < 0.001). Gestational age, chronological age and birth weight of infants were found to be negatively correlated with CCT at first (r = -0.751, p < 0.001; r = -0.745, p < 0.001; r = 0.581, p < 0.001, consecutively) and second (r = -0.729, p < 0.001; r = -0.729, p < 0.001; r = -0.555, p < 0.001, consecutively) visits. The mean IOP at first and second visits were 14.1 +/- 1.9 (11-19) and 13.7 +/- 1.7 (11-18) mmHg, consecutively (p < 0.001). Gestational age, chronological age, and birth weight of infants were found to be negatively correlated with IOP at first (r = -0.724, p < 0.001; r = -0.715, p < 0.001; r = -0.558, p < 0.001, consecutively) and second (r = -0.704, p < 0.001; r = -0.703, p < 0.001; r = -0.518, p < 0.001, consecutively) visits. CCT and IOP of the premature infants with a smaller gestational age were found to be higher (p < 0.001 for both). Premature infants with smaller gestational age have higher CCT and IOP values when compared to older infants. These values tend to become lower 4 weeks after the first examination as infants become older. The CCT and IOP were positively correlated with each other and both were negatively correlated with gestational age, chronological age, and birth weight during first and second visits. PMID- 26286759 TI - The impact of paternal factors on cleavage stage and blastocyst development analyzed by time-lapse imaging-a retrospective observational study. AB - PURPOSE: Various time-lapse studies have postulated embryo selection criteria based on early morphokinetic markers. However, late paternal effects are mostly not visible before embryonic genome activation. The primary objective of this retrospective study was to investigate whether those early morphokinetic algorithms investigated by time-lapse imaging are reliable enough to allow for the accurate selection of those embryos that develop into blastocysts, while of course taking into account the correlation with the type of injected spermatozoa. METHODS: During a period of 18 months, a total of 461 MII oocytes from 43 couples with severe male factor infertility and previous "external" IVF failures after cleavage-stage embryo transfer (ET) were fertilized by intracytoplasmic morphologically selected sperm injection (IMSI). Thereof, 373 embryos were monitored in a time-lapse incubator until ET on day 5. Blastocyst outcome in combination with three previously postulated MKc (cc2: t3-t2, 5-12 h; t3, 35-40 h; t5, 48-56 h) and the morphology of the selected sperm were analyzed. RESULTS: A significant increase in the rate of blastocysts (54.0 vs. 36.3 %; P < 0.01) and top blastocysts (25.3 vs. 10.8 %; P < 0.001) was observed in the group of those meeting all three morphokinetic criteria (MKc3). However, MKc3 were only met in 23.3 % of all embryos. Moreover, TBR was influenced by the type of injected spermatozoa. In both groups, TBR decreased dramatically (MKc3, 35.0 vs. 17.0 %; MKc < 3, 14.2 vs. 8.4 %) when class II/III sperm instead of class I were injected. CONCLUSION: Early morphokinetic parameters might give some predictive information but fail to serve as a feasible selective tool for the prediction of blastocyst development given the influence of the type of spermatozoa injected. PMID- 26286760 TI - Effects of bevacizumab loaded PEG-PCL-PEG hydrogel intracameral application on intraocular pressure after glaucoma filtration surgery. AB - PEG-PCL-PEG (PECE) hydrogel for intracameral injection as a sustained delivery system can get a stable release of the medication and achieve an effective local concentration. The injectable PECE hydrogel is thermosensitive nano-material which is flowing sol at low temperature and can shift to nonflowing gel at body temperature. This study evaluated the intracameral injection of bevacizumab combined with a PECE hydrogel drug release system on postoperative scarring and bleb survival after experimental glaucoma filtration surgery. The best result was achieved in the bevacizumab loaded PECE hydrogels group, which presented the lowest IOP values after surgery. And the blebs were significantly more persistent in this group. Histology, Massion trichrome staining and immunohistochemistry further demonstrated that glaucoma filtration surgery in combination with bevacizumab loaded PECE hydrogel resulted in good bleb survival due to scar formation inhibition. In conclusions, this study demonstrated that bevacizumab loaded PECE hydrogel for intracameral injection as a sustained delivery system provide a great opportunity to increase the therapeutic efficacy of glaucoma filtration surgery. PMID- 26286762 TI - Molecular Orientation in Stable Glasses of Indomethacin. AB - Spectroscopic ellipsometry has been used to measure the properties of indomethacin prepared by physical vapor deposition at Tsubstrate/Tg = 0.78, 0.84, and 0.90. The as-deposited glasses exhibited high kinetic stability and had densities 0.8-1.2% higher than the ordinary glass prepared by cooling the liquid at 1 K/min. Deposition at the higher temperatures yielded glasses with positive birefringence (up to Deltan = 0.028), while the lowest-temperature sample was negatively birefringent (Deltan = -0.015). These results indicate that substrate temperature can be used to manipulate molecular orientation in high-density and high-stability glasses. The data for the supercooled liquid and the ordinary glass of indomethacin are reasonably consistent with the Lorentz-Lorenz equation, but significant deviations are noted with the as-deposited materials. PMID- 26286761 TI - Antibiosis of Necrotizing Pancreatitis. AB - BACKGROUND: Necrotizing pancreatitis is a life-threatening presentation of acute pancreatitis. The mortality of 20-80% initially depends on the persistence of organ failure and systemic inflammatory response syndrome (SIRS) and, in the later course of the disease, on secondary infection of the necrosis. The questions whether prophylactic antibiotics aiming to prevent this infection should be administered and which antibiotic is the best to use, as well as the problem of fungal infection under antibiotic treatment are still intriguing and insufficiently solved. METHODS: A search of the literature using PubMed was carried out, supplemented by a review of the programmes of the Digestive Disease Week (DDW) and the United European Gastroenterology Week (UEGW). RESULTS: Despite the widely practised prophylactic antibiotic administration in severe pancreatitis, no evidence for the benefit of this strategy exists. One of the drawbacks might be a tendency for disastrous fungal infection under prophylactic antibiotics. Bacterial translocation from the gut in the second week after the onset of symptoms is the major source for infection of pancreatic necrosis and provides a clear indication for antibiotic treatment. However, routine fine needle aspiration for a calculated antibiotic therapy cannot be recommended, and all other tests offer only indirect signs. Important factors such as enteral versus parenteral feeding and the method of necrosectomy are mostly neglected in the trials but seem to be essential for the outcome of the patient. CONCLUSIONS: Even though most meta-analyses including the newer double-blind, placebo controlled trials on prophylactic antibiotics showed no beneficial effects in the prevention of infection of necrosis and/or outcome of the patients, this strategy is still widely used in clinical routine. Since nearly all trials published so far show systematic problems (i.e. inaccurate definition of the severity of the disease, poor statistical testing, and neglect of differences in the route of nutrition), there is a need for randomized controlled prospective trials with exact definitions of the disease. PMID- 26286763 TI - Realization of Associative Memory in an Enzymatic Process: Toward Biomolecular Networks with Learning and Unlearning Functionalities. AB - We report a realization of an associative memory signal/information processing system based on simple enzyme-catalyzed biochemical reactions. Optically detected chemical output is always obtained in response to the triggering input, but the system can also "learn" by association, to later respond to the second input if it is initially applied in combination with the triggering input as the "training" step. This second chemical input is not self-reinforcing in the present system, which therefore can later "unlearn" to react to the second input if it is applied several times on its own. Such processing steps realized with (bio)chemical kinetics promise applications of bioinspired/memory-involving components in "networked" (concatenated) biomolecular processes for multisignal sensing and complex information processing. PMID- 26286764 TI - Quantifying the Structural Dynamics of Pharmaceuticals in the Glassy State. AB - Structural dynamics in the glassy state of two protic ionic liquids, carvedilol phosphate and procaine hydrochloride, were characterized from analysis of changes in the conductivity relaxation times during physical aging. The obtained relaxation times, having a magnitude exceeding feasible experimental time scales and thus not directly measurable, are consistent with published data from a method that relies on the presence of a secondary relaxation. We also observe a narrowing of the relaxation dispersion, specific to higher frequencies, that is a consequence of the heterogeneous dynamics of deeply supercooled materials. PMID- 26286765 TI - Influence of Lithium Salts on the Discharge Chemistry of Li-Air Cells. AB - In this work, we show that the use of a high boiling point ether solvent (tetraglyme) promotes the formation of Li2O2 in a lithium-air cell. However, another major constituent in the discharge product of a Li-air cell contains halides from the lithium salts and C-O from the tetraglyme used as the solvent. This information is critical to the development of Li-air electrolytes, which are stable and promote the formation of the desired Li2O2 products. PMID- 26286766 TI - Near-Infrared Plasmon-Assisted Water Oxidation. AB - We report the stoichiometric evolution of oxygen via water oxidation by irradiating a plasmon-enhanced photocurrent generation system with near-infrared light (lambda: 1000 nm), in which gold nanostructures were arrayed on the surface of TiO2 electrode. It is considered that multiple electron holes generated by plasmon-induced charge excitation led to the effective recovery of water oxidation after the electron transfer from gold to TiO2. The proposed system containing a gold nanostructured TiO2 electrode may be a promising artificial photosynthetic system using near-infrared light. PMID- 26286767 TI - Influence of Processing Additives on Charge-Transfer Time Scales and Sound Velocity in Organic Bulk Heterojunction Films. AB - The role of processing additives in organic bulk heterojunction thin films was investigated by means of transient absorption spectroscopy. The rate of ultrafast charge transfer was found to increase when a small amount of diiodooctane was used during film formation. In addition, coherent acoustic phonons were observed, and their velocity was determined. A strong correlation between the sound velocity and the charge-transfer time scale was observed, both of which could be explained by a subtle increase in thin film density. PMID- 26286768 TI - Does Solution Viscosity Scale the Rate of Aggregation of Folded Proteins? AB - Viscosity effects on the kinetics of complex solution processes have proven hard to predict. To test the viscosity effects on protein aggregation, we use the crystallization of the protein glucose isomerase (gluci) as a model and employ scanning confocal and atomic force microscopies at molecular resolution, dynamic and static light scattering, and rheometry. We add glycerol to vary solvent viscosity and demonstrate that glycerol effects on the activation barrier for attachment of molecules to the crystal growth sites are minimal. We separate the effects of glycerol on crystallization thermodynamics from those on the rate constant for molecular attachment. We establish that the rate constant is proportional to the reciprocal viscosity and to the protein diffusivity. This finding refutes the prevailing crystal growth paradigm and illustrates the application of fundamental kinetics laws to solution crystallization. PMID- 26286769 TI - Thermal Tuning and Inversion of Excitonic Zeeman Splittings in Colloidal Doped CdSe Quantum Dots. AB - Variable-temperature magnetic circular dichroism (MCD) spectroscopy is used to measure excitonic Zeeman splittings in colloidal Co(2+)- and Mn(2+)-doped CdSe quantum dots with low dopant concentrations. The data demonstrate that the competition between intrinsic and exchange contributions to the excitonic Zeeman splittings in doped quantum dots can be tuned using temperature, from being dominated by exchange at low temperatures to being dominated by intrinsic Zeeman interactions at room temperature, with inversion at easily accessible temperatures and fields. These results may have relevance to spin-based information processing technologies that rely on manipulating carrier spins in quantum dots. PMID- 26286770 TI - Specific Cation Effects on the Bimodal Acid-Base Behavior of the Silica/Water Interface. AB - Using nonresonant second harmonic generation spectroscopy, we have monitored the change in surface charge density of the silica/water interface over a broad pH range in the presence of different alkali chlorides. Planar silica is known to possess two types of surface sites with pKa values of ~4 and ~9, which are attributed to different solvation environments of the silanols. We report that varying the alkali chloride electrolyte significantly changes the effective acid dissociation constant (pKa(eff)) for the less acidic silanol groups, with the silica/NaClaq and silica/CsClaq interfaces exhibiting the lowest and highest pKa(eff) values of 8.3(1) and 10.8(1), respectively. Additionally, the relative populations of the two silanol groups are also very sensitive to the electrolyte identity. The greatest percentage of acidic silanol groups was 60(2)% for the silica/LiClaq interface in contrast to the lowest value of 20(2)% for the silica/NaClaq interface. We attribute these changes in the bimodal behavior to the influence of alkali ions on the interfacial water structure and its corresponding effect on surface acidity. PMID- 26286771 TI - Plasmonic Near-Field Absorbers for Ultrathin Solar Cells. AB - If the active layer of efficient solar cells could be made 100 times thinner than in today's thin film devices, their economic competitiveness would greatly benefit. However, conventional solar cell materials do not have the optical capability to allow for such thickness reductions without a substantial loss of light absorption. To address this challenge, the use of plasmon resonances in metal nanostructures to trap light and create charge carriers in a nearby semiconductor material is an interesting opportunity. In this Perspective, recent progress with regards to ultrathin (~10 nm) plasmonic nanocomposites is reviewed. Their optimal internal geometry for plasmon near-field induced absorption is discussed, and a zero thickness effective medium representation is used to optimize stacks including an Al back reflector for photovoltaics. This shows that high conversion efficiencies (>20%) are possible even when taking surface scattering effects and thin passivating layers inserted between the metal and semiconductor into account. PMID- 26286772 TI - Shedding Light on Surface-Enhanced Raman Scattering Hot Spots through Single Molecule Super-Resolution Imaging. AB - Super-resolution imaging has recently been utilized to develop a better understanding of the properties of surface-enhanced Raman scattering (SERS) hot spots. SERS hot spots are much smaller than the diffraction limit of light, and therefore, obtaining a clear picture of the enhanced electromagnetic (EM) fields comprising these hot spots is a challenging task. In this Perspective, we discuss recent work applying super-resolution imaging to single-molecule SERS (SM-SERS) of rhodamine 6G (R6G) adsorbed to randomly assembled silver colloidal aggregates, allowing the shape, size, and local enhancement of the hot spots to be imaged with <5 nm resolution. The results are compared with studies applying super resolution imaging to surface-enhanced fluorescence (SEF) of analytes diffusing into silver nanoparticle hot spots. Both studies show a strong correlation between emission intensity and position, allowing the EM field enhancements of SERS hot spots to be mapped with sub-5 nm resolution. PMID- 26286773 TI - Polarization-Controlled Raman Microscopy and Nanoscopy. AB - Polarization imaging reveals unique characteristics of samples, such as molecular symmetry, orientation, or intermolecular interactions. Polarization techniques extend the ability of conventional spectroscopy to enable the characterization and identification of molecular species. In the early days of spectroscopy, it was considered that a set of polarizers placed in the illumination and the detection paths was enough to enable polarization analysis. However, with the development of new microscope imaging techniques, such as high-resolution microscopy, nonlinear spectroscopic imaging, and near-field microscopy, the inevitable polarization changes caused by external optical components needs to be discussed. In this Perspective, we present some of the hot topics that are specific to high-spatial-resolution microscopy and introduce recent related work in the field. Among the many spectroscopic techniques available, we focus in particular on Raman spectroscopy because Raman tensors are widely used in pure and applied sciences to study the symmetry of matter. PMID- 26286774 TI - The Surface Chemistry of Atomic Layer Depositions of Solid Thin Films. AB - Atomic layer deposition (ALD) is one of the most promising methodologies available for the growth of solid thin films conformally on complex topographies and with atomic-level control on thickness. However, as a chemical process, ALD can lead to the incorporation of impurities and to the growth of poor-quality films. Here we discuss some possible complications associated with the chemistry of ALD, including its ill-defined stoichiometry, the stepwise and extensive surface conversion possible with the ligands of most ALD metalorganic precursors, the need for the reduction or oxidation of the deposited elements, the poor understanding of the role of the coreactants, the dominant activity of specific minority surface sites in starting ALD processes, and the development of complex layered or three-dimensional structures within the deposited films. The resolution of these issues should help with the development of a more systematic approach for the selection of ALD precursors and for the design of ALD processes. PMID- 26286775 TI - Imaging the O((1)D) + CD4 -> OD + CD3 Reaction Dynamics: The Threshold of Abstraction Pathway. AB - The O((1)D) + CD4 -> OD + CD3 reaction was investigated using the crossed molecular beam technique with sliced velocity map imaging at four different collision energies: 1.6, 2.8, 4.6, and 6.8 kcal/mol. The vibrational ground state product CD3 was detected using a (2 + 1) resonance-enhanced multiphoton ionization (REMPI). Remarkably different features were found in the forward and backward scatterings, and gradually changed with the collision energy. These features were attributed to two distinctive reaction mechanisms-insertion and abstraction-that occur on the ground and excited state surfaces, respectively. Contributions from the two mechanisms were extracted from the experiment results, and a positive correlation was found between the abstraction proportion and the collision energy. The threshold for the abstraction pathway was determined and compared with results from calculations. PMID- 26286776 TI - Liquid Crystal Phases in Suspensions of Charged Plate-Like Particles. AB - Anisotropic interactions in colloidal suspensions have recently emerged as a route for the design of new soft materials. Nonisotropic particles can form nematic, smectic, hexatic, and columnar liquid crystals. Although the formation of these phases is well rationalized when excluded volume is solely at play, the role of electrostatic interactions still remains unclear and even less so when particles present a charge heterogeneity, for example, clays. Here, we use Monte Carlo simulations of concentrated suspensions of charged disk-like particles to reveal the role of Coulomb interactions and charge anisotropy underlying liquid crystal formation and structures. We observe a vast zoo of exotic structures, going from hexatic to columnar phases, which are shown to be controlled by the charge anisotropy. The particle volume fraction at which these phases start to form is found to decrease with increasing Coulomb interactions and charge anisotropy, which suggests a route to tune the structure of aqueous liquid crystals. PMID- 26286777 TI - Exciton Conformational Dynamics of Poly(3-hexylthiophene) (P3HT) in Solution from Time-Resolved Resonant-Raman Spectroscopy. AB - We have used time-resolved resonant-Raman spectroscopy to investigate the picosecond conformational relaxation of regioregular poly(3-hexylthiophene) (RR P3HT) in chlorobenzene after 510 nm photoexcitation. Vibrational signatures from modes along and peripheral to the exciton's backbone have been identified according to the time dependence of excited-state Raman features and from comparisons to Raman spectra of other polymer states. Measured spectral dynamics reflect initial changes in the resonance enhancement of backbone modes on a time scale of 9 +/- 1 ps. In contrast, contributions from peripheral modes exhibit time-dependent decay determined only by exciton intersystem-crossing kinetics. Spectral dynamics are interpreted in terms of evolution in bond lengths along the exciton's backbone resulting from increased conjugation allowed by torsional reordering. Possible origins of peripheral features are discussed, including distorted inter-ring modes at exciton termini. Findings provide a glimpse of the underlying molecular dynamics responsible for the red shift in the exciton's near IR transient absorption occurring on the same time scale. PMID- 26286778 TI - Optical Response of Fluorescent Molecules Studied by Synthetic Femtosecond Laser Pulses. AB - The optical response of the fluorescent molecule IR144 in solution is probed by pairs of collinear pulses with intensity just above the linear dependence using two different pulse shaping methods. The first approach mimics a Michelson interferometer, while the second approach, known as multiple independent comb shaping (MICS), eliminates spectral interference. The comparison of interfering and non-interfering pulses reveals that linear interference between the pulses leads to the loss of experimental information at early delay times. In both cases, the delay between the pulses is controlled with attosecond resolution and the sample fluorescence and stimulated emission are monitored simultaneously. An out-of-phase behavior is observed for fluorescence and stimulated emission, with the fluorescence signal having a minimum at zero time delay. Experimental findings are modeled using a two-level system with relaxation that closely matches the phase difference between fluorescence and stimulated emission and the relative intensities of the measured effects. PMID- 26286779 TI - Multiple Pathway Relaxation Enhancement in the System Composed of Three Paramagnetic Species: Nitroxide Radical-Ln(3+)-O2. AB - Longitudinal relaxation of nitroxide spin-labels has been measured for a membrane incorporated alpha-helical polypeptide in the presence and absence of residual amounts of membrane-dissolved O2 and paramagnetic Dy(3+) ions. Such a model system, containing three different types of paramagnetic species, provides an important example of nonadditivity of two different relaxation channels for the nitroxide spins. PMID- 26286780 TI - Observation of NH X(3)Sigma(-) as a Primary Product of Methylamine Photodissociation: Evidence of Roaming-Mediated Intersystem Crossing? AB - 3+1 Resonance-enhanced multiphoton ionization and photofragment excitation spectroscopy have been used to identify NH X(3)Sigma(-) as a primary product of methylamine photodissociation after state-specific excitation to the S1 state. On the basis of standard thermochemical data, NH X(3)Sigma(-) can be formed only in conjunction with closed-shell CH4 coproducts, indicating that dissociation must occur on the T1 surface. It is proposed that the mechanism for the formation of triplet NH and CH4 involves intramolecular abstraction between frustrated radical products and is an example of roaming-mediated intersystem crossing. PMID- 26286781 TI - Polymer Single Crystal As Magnetically Recoverable Support for Nanocatalysts. AB - In this Letter, we report, for the first time, using polymer single crystal as magnetically recoverable support for nanoparticle catalysts. This catalyst system is composed of polymer single crystal, platinum nanoparticles, and iron oxide nanoparticles, which act as support, catalysts, and magnetic responsive materials, respectively. Platinum nanoparticles and iron oxide nanoparticles were bonded onto thiol groups and hydroxyl groups on a tailor-designed polymer single crystal surface. Because of its quasi 2D nature, polymer single crystal possesses high surface area to volume ratio (2.5 * 10(8) m(-1)), which is ~40 times higher than its nanosphere counterpart of the same volume. This high surface to volume ratio facilitates the high loading of both nanoparticles, which ensures efficient catalytic reaction and reliable nanoparticle recycling. Synergetic interactions between platinum and iron oxide nanoparticles also led to further improvement in catalytic activity. PMID- 26286782 TI - Toward Antimony Selenide Sensitized Solar Cells: Efficient Charge Photogeneration at spiro-OMeTAD/Sb2Se3/Metal Oxide Heterojunctions. AB - Photovoltaic devices comprising metal chalcogenide nanocrystals as light harvesting components are emerging as a promising power-generation technology. Here, we report a strategy to evenly deposit Sb2Se3 nanoparticles on mesoporous TiO2 as confirmed by Raman spectroscopy, energy-dispersive X-ray spectrometry, and transmission electron microscopy. Detailed study of the interfacial charge transfer dynamics by means of transient absorption spectroscopy provides evidence of electron injection across the Sb2Se3/TiO2 interface upon illumination, which can be improved 3-fold by annealing at low temperatures. Following addition of the spiro-OMeTAD hole transporting material, regeneration yields exceeding 80% are achieved, and the lifetime of the charge separated species is found to be on the millisecond time scale (tau50% ~ 50 ms). These findings are discussed with respect to the design of solid-state Sb2Se3 sensitized solar cells. PMID- 26286783 TI - Harnessing Chemical Raman Enhancement for Understanding Organic Adsorbate Binding on Metal Surfaces. AB - Surface-enhanced Raman spectroscopy (SERS) is a known approach for detecting trace amounts of molecular species. Whereas SERS measurements have focused on enhancing the signal for sensing trace amounts of a chemical moiety, understanding how the substrate alters molecular Raman spectra can enable optical probing of analyte binding chemistry. Here we examine binding of trans-1,2-two(4 pyridyl) ethylene (BPE) to Au surfaces and understand variations in experimental data that arise from differences in how the molecule binds to the substrate. Monitoring differences in the SERS as a function of incubation time, a period of several hours in our case, reveals that the number of BPE molecules that chemically binds with the Au substrate increases with time. In addition, we introduce a direct method of accessing relative chemical enhancement from experiments that is in quantitative agreement with theory. The ability to probe optically specific details of metal/molecule interfaces opens up possibilities for using SERS in chemical analysis. PMID- 26286784 TI - Biomimetic Carbon Nanotube for Catalytic CO2 Hydrolysis: First-Principles Investigation on the Role of Oxidation State and Metal Substitution in Porphyrin. AB - Hydrolysis of carbon dioxide is an important reaction for CO2 collection. Using accurate first-principles electronic structure calculations, we predict how the catalytic hydrolysis reaction in carbonic anhydrase (CA) can be mimicked in a metal-porphyrin carbon nanotube. The two-step catalytic process can be improved remarkably by controlling the porphyrin oxidation state via the nanotube charge state and by substituting the porphyrin metal atom. The oxidation state and the metal substitution both have profound effects on the reaction energetics for the initial hydration reaction step. For the subsequent product-release reaction step, two different reaction mechanisms could take place. These mechanisms are distinctively sensitive to either the oxidation state change or the metal substitution, but not to both. For the overall catalytic cycle, a significant dependence on the nanotube charge state at low pH and on the metal substitution at high pH is expected. PMID- 26286785 TI - Ferromagnetism in p-Type Manganese-Doped Zinc Oxide Quantum Dots. AB - The magnetic exchange interactions between paramagnetic Mn(2+) dopants in the presence of a N(2-) p-type defect in zinc oxide quantum dots are studied using density functional theory. Spin-dependent delocalization of the N(2-) 2p acceptor level among the nearest-neighbor Mn(2+) dopants is observed. The calculations show that parallel Mn(2+) spin alignment is favored upon the formation of a nitrogen-bridged Mn-Mn dimer. Although the effect is short-ranged, the observed magnitude of stabilization of the ferromagnetic alignment of nearest-neighbor Mn(2+) spins arises from p-d exchange and suggests p-type Mn(2+)-doped ZnO quantum dots as excellent candidates for exhibiting room-temperature ferromagnetism. Analytical expressions are derived and supported by density functional theory calculations that show that the N(2-) concentration has a stronger influence on the magnetic splitting compared with that of the Mn(2+) concentration. PMID- 26286786 TI - Delocalized Lattice Plasmon Resonances Show Dispersive Quality Factors. AB - This Letter describes how out-of-plane lattice plasmon (OLP) resonances in 2D Au nanoparticle (NP) arrays show dispersive quality factors. These quality factors can be tailored simply by controlling NP height. Numerical calculations of near field optical properties and band diagrams were performed to understand the measured dispersion effects of the OLPs. The results revealed that delocalized OLPs are a type of surface Bloch mode composed of many Bloch harmonics. As the OLP dispersion evolves from a stationary state to a propagating state, the nonradiative loss decreases because of weak local field confinement, whereas the radiative loss increases because of strong coupling to the leaky zero-order harmonic. PMID- 26286787 TI - Recombination in Organic Bulk Heterojunction Solar Cells: Small Dependence of Interfacial Charge Transfer Kinetics on Fullerene Affinity. AB - We investigate the causes for obtaining higher open-circuit voltage in solar cells that use a fullerene with a smaller electron affinity. Using impedance spectroscopy technique, we show that the change of fullerene LUMO energy has very little influence on the kinetic rate of charge transfer across the interface. In terms of the Marcus theory, large reorganization energy values govern the recombination kinetic rate, which is only slightly dependent on the fullerene LUMO energy, and also depends weakly on the energy location of recombining carriers within the broad density of states. Since the recombination rate is very similar in the different devices, we conclude that the larger open-circuit voltage is due to the larger donor HOMO/acceptor LUMO offset. PMID- 26286788 TI - Enhancing the Sensitivity of Single-Particle Photothermal Imaging with Thermotropic Liquid Crystals. AB - Individual molecules and nanoparticles can be imaged based on their absorption using photothermal microscopy. This technique relies on the heating-induced changes in the refractive index of the surrounding medium. Here, we demonstrate an order of magnitude larger enhancement of the signal-to-noise ratio in photothermal imaging of 20 nm gold nanoparticles when using a thermotropic liquid crystal (5CB). We show quantitatively that this increase is due to the large change in the thermo-optical properties of 5CB mainly along the nematic director. Enhancing the sensitivity is important for the further development of absorption based single-molecule spectroscopy techniques. PMID- 26286789 TI - Nanoscale Thermotropic Phase Transitions Enhancing Photothermal Microscopy Signals. AB - The photothermal heterodyne imaging technique enables studies of individual weakly absorbing nano-objects in various environments. It uses a photoinduced change in the refractive index of the environment. Taking advantage of the dramatic index of refraction change occurring around a thermotropic liquid crystalline phase transition, we demonstrate a 40-fold signal-to-noise ratio enhancement for gold nanoparticles imaged in 4-cyano-4'-pentylbiphenyl (5CB) liquid crystals over those in a water environment. We studied the photothermal signal as a function of probe laser polarization, heating power, and sample temperature quantifying the optimal enhancement. This study established photothermal microscopy as a valuable technique for inducing and/or detecting local phase transitions at the nanometer scales. PMID- 26286790 TI - Rubidium on Helium Droplets: Analysis of an Exotic Rydberg Complex for n* < 20 and 0 <= l <= 3. AB - Rubidium atom Rydberg states perturbed by helium droplets of different sizes provide insight into the role of a nanosized dielectric on the Coulomb potential. The observation of droplet size-dependent shifts of excited states with respect to bare atom states is explained by a decreased quantum defect and a lowered ionization threshold. Within the scope of a Rydberg model, we demonstrate that quantum defects and ionization potentials are constant for each specific Rydberg series, which confirms the Rydberg character of excited Rubidium states on helium droplets. A set of six Rydberg series could be identified. Individual Rydberg states are observed with effective principal quantum numbers up to n* ~ 19 and l <= 3, for which the expectation value of the electron orbital radius is about 10 times larger than the droplet radius. PMID- 26286791 TI - Carbon-Detected (15)N NMR Spin Relaxation of an Intrinsically Disordered Protein: FCP1 Dynamics Unbound and in Complex with RAP74. AB - Intrinsically disordered proteins (IDPs) lack unique 3D structures under native conditions and as such exist as highly dynamic ensembles in solution. We present two (13)C-direct detection experiments for the measurement of (15)N NMR spin relaxation called the CON(T1)-IPAP and CON(T2)-IPAP that quantify backbone dynamics on a per-residue basis for IDPs in solution. These experiments have been applied to the intrinsically disordered C-terminal of FCP1, both free in solution and while bound to the RAP74 winged-helix domain. The results provide evidence that most of FCP1 remains highly dynamic in both states, while the 20 residues forming direct contact with RAP74 become more ordered in the complex. Parallel analysis of RAP74 backbone (15)N NMR spin relaxation reveals only very limited ordering of RAP74 upon FCP1 binding. Taken together, these data show that folding upon-binding is highly local in this system, with disorder prevailing even in the complex. PMID- 26286792 TI - Structures of (3n-Crown-n)-Phenol (n = 4, 5, 6, 8) Host-Guest Complexes: Formation of a Uniquely Stable Complex for n = 6 via Collective Intermolecular Interaction. AB - Structures of crown-phenol 1:1 host-guest complexes, 3n-crown-n [12C4(n = 4), 15C5(n = 5), 18C6(n = 6), 24C8(n = 8)], in the gas phase have been studied by various laser spectroscopic methods. The S1-S0 electronic spectra identified 3, 2, 1, and 2 isomers for the complexes of 12C4, 15C5, 18C6, and 24C8, respectively, suggesting that only 18C6-phenol forms one uniquely stable complex. The IR spectra in the phenolic OH and CH stretch regions indicate that these complexes form the O...HO hydrogen bond, and the benzene ring is involved in the complex formation. Theoretical analysis with molecular mechanics and density functional theory calculations also supports one considerably stable isomer for 18C6-phenol. The most stable 18C6-phenol isomer is largely stabilized through collective intermolecular interaction consisting of O...HO hydrogen bond, CH...pi, and O...HC(aromatic) so that phenol is inserted into the cavity of a particular conformation of 18C6 like a "lock and key". PMID- 26286793 TI - Spectroscopy, Imaging, and Solar Energy Conversion with Plasmons. PMID- 26286795 TI - Pattern of chilblains in a high altitude region of Ladakh, India. AB - BACKGROUND: Extreme sub-zero temperature in winters (15 degrees C to -25 degrees C), high velocity winds and wind-chill factor pose risk to those who resides at the high altitude environment to develop cold related injuries like chilblains and frostbite. The aim of this study was to study the patterns of chilblains in high altitude region like Ladakh. METHODS: The study was conducted at Dermatology outpatient department of Military Hospital, Leh from 1 Sep 2009 to 31 May 2010. Patients, satisfying clinical criteria for the diagnosis of chilblains were included into the study. Detailed history and thorough clinical examination was conducted. Complete blood count and Urine routine examination was carried out in every patient. Anti Nuclear Factor tests were carried out in only those who had history suggestive of connective tissue disease. RESULTS: Total 108 (5.75%) were diagnosed to have chilblains. Only a single case of chilblain was found in a local resident (p < 0.005). Family history of chilblains was present in 10 (9.2%) patients, there was recurrence in 12 (11.1%) and 21 patients (19.4%) were smokers. Most (63.8%) of the patients, had BMI between 20 and 22 kg/m(2) (mean = 20.03 kg/m(2); 95% CI = 19.68-20.38 and SD 1.82). 42.1% of cases of chilblains also had hyperhidrosis (p < 0.05). CONCLUSION: In a HA area like Ladakh, the non-natives suffer maximum from chilblains. This could be explained by the protective genetic adaptability of natives to extreme cold environment and their protective life style against cold. Low body mass index (BMI) and hyperhidrosis are important associations for development of chilblains. PMID- 26286794 TI - Combined PET/MRI: Multi-modality Multi-parametric Imaging Is Here: Summary Report of the 4th International Workshop on PET/MR Imaging; February 23-27, 2015, Tubingen, Germany. AB - This paper summarises key themes and discussions from the 4th international workshop dedicated to the advancement of the technical, scientific and clinical applications of combined positron emission tomography (PET)/magnetic resonance imaging (MRI) systems that was held in Tubingen, Germany, from February 23 to 27, 2015. Specifically, we summarise the three days of invited presentations from active researchers in this and associated fields augmented by round table discussions and dialogue boards with specific topics. These include the use of PET/MRI in cardiovascular disease, paediatrics, oncology, neurology and multi parametric imaging, the latter of which was suggested as a key promoting factor for the wider adoption of integrated PET/MRI. Discussions throughout the workshop and a poll taken on the final day demonstrated that attendees felt more strongly that PET/MRI has further advanced in both technical versatility and acceptance by clinical and research-driven users from the status quo of last year. Still, with only minimal evidence of progress made in exploiting the true complementary nature of the PET and MRI-based information, PET/MRI is still yet to achieve its potential. In that regard, the conclusion of last year's meeting "the real work has just started" still holds true. PMID- 26286796 TI - Antimicrobial resistance of Pseudomonas spp. isolated from wastewater and wastewater-impacted marine coastal zone. AB - In this study, species distribution and antimicrobial susceptibility of cultivated Pseudomonas spp. were studied in influent (INF), effluent (EFF), and marine outfall (MOut) of wastewater treatment plant (WWTP). The susceptibility was tested against 8 antimicrobial classes, active against Pseudomonas spp.: aminoglycosides, carbapenems, broad-spectrum cephalosporins from the 3rd and 4th generation, extended-spectrum penicillins, as well as their combination with the beta-lactamase inhibitors, monobactams, fluoroquinolones, and polymyxins. Among identified species, resistance to all antimicrobials but colistin was shown by Pseudomonas putida, the predominant species in all sampling points. In other species, resistance was observed mainly against ceftazidime, ticarcillin, ticarcillin-clavulanate, and aztreonam, although some isolates of Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas pseudoalcaligenes, and Pseudomonas protegens showed multidrug-resistance (MDR) phenotype. Among P. putida, resistance to beta-lactams and to fluoroquinolones as well as multidrug resistance become more prevalent after wastewater treatment, but the resistance rate decreased in marine water samples. Obtained data, however, suggests that Pseudomonas spp. are equipped or are able to acquire a wide range of antibiotic resistance mechanisms, and thus should be monitored as possible source of resistance genes. PMID- 26286797 TI - The enzymatic and antioxidative stress response of Lemna minor to copper and a chloroacetamide herbicide. AB - Lemna minor L., a widely used model plant for toxicity tests has raised interest for its application to phytoremediation due to its rapid growth and ubiquitous occurrence. In rural areas, the pollution of water bodies with heavy metals and agrochemicals poses a problem to surface water quality. Among problematic compounds, heavy metals (copper) and pesticides are frequently found in water bodies. To establish duckweed as a potential plant for phytoremediation, enzymatic and antioxidative stress responses of Lemna minor during exposure to copper and a chloroacetamide herbicide were investigated in laboratory studies. The present study aimed at evaluating growth and the antioxidative and glutathione-dependent enzyme activity of Lemna plants and its performance in a scenario for phytoremediation of copper and a chloroacetamide herbicide. Lemna minor was grown in Steinberg medium under controlled conditions. Plants were treated with CuSO4 (ion conc. 50 and 100 MUg/L) and pethoxamide (1.25 and 2.5 MUg/L). Measurements following published methods focused on plant growth, oxidative stress, and basic detoxification enzymes. Duckweed proved to survive treatment with the respective concentrations of both pollutants very well. Its growth was inhibited scarcely, and no visible symptoms occurred. On the cellular basis, accumulation of O2(-) and H2O2 were detected, as well as stress reactions of antioxidative enzymes. Duckweed detoxification potential for organic pollutants was high and increased significantly with incubation. Pethoxamide was found to be conjugated with glutathione. Copper was accumulated in the fronds at high levels, and transient oxidative defense reactions were triggered. This work confirms the significance of L. minor for the removal of copper from water and the conjugation of the selective herbicide pethoxamide. Both organic and inorganic xenobiotics induced different trends of enzymatic and antioxidative stress response. The strong increase of stress responses following copper exposure is well known as oxidative burst, which is probably different from the much more long-lasting responses found in plants exposed to pethoxamide. Lemna sp. might be used as a tool for phytoremediation of low-level contamination with metals and organic xenobiotics, however the authors recommend a more detailed analysis of the development of the oxidative burst following copper exposure and of the enzymatic metabolism of pethoxamide in order to elucidate the extent of its removal from water. PMID- 26286798 TI - Physicochemical profile of microbial-assisted composting on empty fruit bunches of oil palm trees. AB - This study was carried out to investigate the physicochemical properties of compost from oil palm empty fruit bunches (EFB) inoculated with effective microorganisms (EM?1TM). The duration of microbial-assisted composting was shorter (~7 days) than control samples (2 months) in a laboratory scale (2 kg) experiment. The temperature profile of EFB compost fluctuated between 26 and 52 degrees C without the presence of consistent thermophilic phase. The pH of compost changed from weak acidic (pH ~5) to mild alkaline (pH ~8) because of the formation of nitrogenous ions such as ammonium (NH4 (+)), nitrite (NO2 (-)), and nitrate (NO3 (-)) from organic substances during mineralization. The pH of the microbial-treated compost was less than 8.5 which is important to prevent the loss of nitrogen as ammonia gas in a strong alkaline condition. Similarly, carbon mineralization could be determined by measuring CO2 emission. The microbial treated compost could maintain longer period (~13 days) of high CO2 emission resulted from high microbial activity and reached the threshold value (120 mg CO2 C kg(-1) day(-1)) for compost maturity earlier (7 days). Microbial-treated compost slightly improved the content of minerals such as Mg, K, Ca, and B, as well as key metabolite, 5-aminolevulinic acid for plant growth at the maturity stage of compost. Graphical Abstract Microbial-assisted composting on empty fruit bunches. PMID- 26286799 TI - Groundwater screening for 940 organic micro-pollutants in Hanoi and Ho Chi Minh City, Vietnam. AB - Groundwater is the main source of drinking water for more than half of the residents of Hanoi (HN). It also provides about one third of the total water demand for residents of Ho Chi Minh City (HCM). However, due to rapid urbanization and frequent discharges of untreated urban wastewater to surface water, freshwater is widely contaminated by man-made chemicals, which may result in groundwater pollution. As part of an ongoing campaign to collect baseline information on the occurrence of organic micro-pollutants (OMPs) in the aquatic environment in Vietnam, 43 water samples were collected from 26 groundwater wells in HN (22) and HCM (4) in September 2013 and August 2014. Samples were analyzed by gas chromatography-mass spectrometry (GC-MS) and the resulting chromatograms were screened for 940 OMPs by an automated identification and quantification system (AIQS) within a GC-MS database. A total of 74 compounds were detected, with between 4 and 43 (median 18) compounds found at each site. Overall, contamination levels were low, with over 89 % of the detected concentrations that were less than 0.5 MUg L(-1). Results suggest that most of the sampled aquifers have been impacted by non-point source pollution. Most of the contaminants detected are either currently not regulated in drinking water or are present at low levels. A health risk assessment for detected contaminants implied that there were no risks to humans. Since this study was based on a limited number of samples, especially in HCM, further, more detailed studies on the occurrence of OMPs in groundwater in HCM and a full risk assessment of detected contaminants should be prioritized. PMID- 26286800 TI - Threats to water resources from hexachlorobenzene waste at Kalush City (Ukraine)- a review of the risks and the remediation options. AB - The production of chlorinated solvents such as tetrachloroethylene and tetrachloromethane has resulted in large stockpiles of unintentionally produced persistent organic pollutants (POPs) including high content of hexachlorobenzene (HCB waste). HCB waste of 15,000 t arising from the production of chlorinated solvents at the Kalush factory in Ukraine was landfilled. In 2008, it was discovered that HCB and other pollutants were escaping from the landfill into local environment including the Sapogi-Limnytsia Rivers, tributaries of the Dniester River. This showed that the HCB waste was not appropriately contained and represented a threat to the Dniester River basin. A Presidential Decree of Ukraine was therefore issued requiring remediation of the site and excavation of the waste. Between 2010 and 2013, approximately 29,445 t of HCB waste and associated contaminated soil was excavated and exported to various EU countries for incineration. This excavation revealed that these wastes can corrode through their drums within a few decades with release of pollutants. Other sites at which chlorinated solvents were produced should therefore be assessed for possible similar pollution. Despite the remediation efforts and the excavation of the landfill, the Kalush area remains a POP-contaminated site requiring further assessment. A part of the waste was exported to Poland and is stored close to the Baltic Sea and is treated in an incinerator with small capacity over a time frame of years. This case and recent similar cases reveal that the control of POP waste for destruction even in EU countries needs to be improved. PMID- 26286801 TI - Preparation and characterization of green bricks using pharmaceutical industrial wastes. AB - This paper reports on recycling of industrial wastes (three pharmaceutical industrial sludges) into environmental friendly value-added materials. Stabilization/Solidification (S/S or bricks) process was applied to make a safer way for the utilization of pharmaceutical waste. The additives in this study include binders (cement, lime and bentonite) and strengthening material (pulverized fuel ash (PFA), silica fume and quarry dust) was used at different compositions. Bricks were cured for 28 days, and the following analysis-like compressive strength, leachability of heavy metals, mineralogical phase identity by X-ray diffraction (XRD) spectroscopy, Fourier transform infrared spectroscopy (FTIR) and thermal behaviour by thermogravimetric-differential thermal analysis (TG-DTA) had done. All the bricks were observed to achieve the standard compressive strength as required for construction according to BIS standards. Metal concentration in the leachate has reached the dischargeable limits according to Brazilian standards. Results of this study demonstrate that production of bricks is a promising and achievable productive use of pharmaceutical sludge. PMID- 26286802 TI - Comparative analyses of genotoxicity, oxidative stress and antioxidative defence system under exposure of methyl parathion and hexaconazole in barley (Hordeum vulgare L.). AB - The present study aims to evaluate the comparative effects of methyl parathion and hexaconazole on genotoxicity, oxidative stress, antioxidative defence system and photosynthetic pigments in barley (Hordeum vulgare L. variety karan-16). The seeds were exposed with three different concentrations, i.e. 0.05, 0.1 and 0.5 % for 6 h after three pre-soaking durations 7, 17 and 27 h which represents G1, S and G2 phases of the cell cycle, respectively. Ethyl methane sulphonate, a well known mutagenic agent and double distilled water, was used as positive and negative controls, respectively. The results indicate significant decrease in mitotic index with increasing concentrations of pesticides, and the extent was higher in methyl parathion. Chromosomal aberrations were found more frequent in methyl parathion than hexaconazole as compared to their respective controls. Treatment with the pesticides induced oxidative stress which was evident with higher contents of H2O2 and lipid peroxidation, and the increase was more prominent in methyl parathion. Contents of total phenolics were increased; however, soluble protein content showed a reverse trend. Among the enzymatic antioxidants, activities of superoxide dismutase and peroxidase were significantly up-regulated, and more increase was noticed in hexaconazole. Increments in total chlorophyll and carotenoid contents were observed up to 0.1 % but decreased at higher concentration (0.5 %), and the reductions were more prominent in methyl parathion than hexaconazole as compared to their respective controls. Methyl parathion treatment caused more damage in the plant cells of barley as compared to hexaconazole, which may be closely related to higher genotoxicity and oxidative stress. PMID- 26286803 TI - Determining soil enzyme activities for the assessment of fungi and citric acid assisted phytoextraction under cadmium and lead contamination. AB - Microorganism or chelate-assisted phytoextraction is an effective remediation tool for heavy metal polluted soil, but investigations into its impact on soil microbial activity are rarely reported. Consequently, cadmium (Cd)- and lead (Pb) resistant fungi and citric acid (CA) were introduced to enhance phytoextraction by Solanum nigrum L. under varied Cd and Pb pollution levels in a greenhouse pot experiment. We then determined accumulation of Cd and Pb in S. nigrum and the soil enzyme activities of dehydrogenase, phosphatase, urease, catalase, sucrase, and amylase. Detrended canonical correspondence analysis (DCCA) was applied to assess the interactions between remediation strategies and soil enzyme activities. Results indicated that the addition of fungi, CA, or their combination enhanced the root biomass of S. nigrum, especially at the high pollution level. The combined treatment of CA and fungi enhanced accumulation of Cd about 22-47 % and of Pb about 13-105 % in S. nigrum compared with the phytoextraction alone. However, S. nigrum was not shown to be a hyperaccumulator for Pb. Most enzyme activities were enhanced after remediation. The DCCA ordination graph showed increasing enzyme activity improvement by remediation in the order of phosphatase, amylase, catalase, dehydrogenase, and urease. Responses of soil enzyme activities were similar for both the addition of fungi and that of CA. In summary, results suggest that fungi and CA-assisted phytoextraction is a promising approach to restoring heavy metal polluted soil. PMID- 26286804 TI - COST action TD1407: network on technology-critical elements (NOTICE)--from environmental processes to human health threats. AB - The current socio-economic, environmental and public health challenges that countries are facing clearly need common-defined strategies to inform and support our transition to a sustainable economy. Here, the technology-critical elements (which includes Ga, Ge, In, Te, Nb, Ta, Tl, the Platinum Group Elements and most of the rare-earth elements) are of great relevance in the development of emerging key technologies-including renewable energy, energy efficiency, electronics or the aerospace industry. In this context, the increasing use of technology critical elements (TCEs) and associated environmental impacts (from mining to end of-life waste products) is not restricted to a national level but covers most likely a global scale. Accordingly, the European COST Action TD1407: Network on Technology-Critical Elements (NOTICE)-from environmental processes to human health threats, has an overall objective for creating a network of scientists and practitioners interested in TCEs, from the evaluation of their environmental processes to understanding potential human health threats, with the aim of defining the current state of knowledge and gaps, proposing priority research lines/activities and acting as a platform for new collaborations and joint research projects. The Action is focused on three major scientific areas: (i) analytical chemistry, (ii) environmental biogeochemistry and (iii) human exposure and (eco)-toxicology. PMID- 26286805 TI - Hospital admissions of hypertension, angina, myocardial infarction and ischemic heart disease peaked at physiologically equivalent temperature 0 degrees C in Germany in 2009-2011. AB - We aimed to understand and to provide evidence on relationships of the weather as biometeorological and hospital admissions due to hypertension, angina, myocardial infarction and ischemic heart disease in a national setting in recent years that might help indicate when to expect more admissions for health professionals and the general public. This is an ecological study. Ten percent of daily hospital admissions from the included hospitals (n = 1618) across Germany that were available between 1 January 2009 and 31 December 2011 (n = 5,235,600) were extracted from Statistisches Bundesamt, Germany. We identified I11 hypertensive heart disease, I13 hypertensive heart and renal disease, I15 secondary hypertension, I20 angina pectoris, I21 acute myocardial infarction and I25 chronic ischemic heart disease by International Classification of Diseases version 10 as the study outcomes. Daily weather data from 64 weather stations that covered 13 German States including air temperature, humidity, wind speed, cloud cover, radiation flux and vapour pressure were obtained and generated into physiologically equivalent temperature (PET). Two-way fractional-polynomial prediction was plotted with 95% confidence intervals. Hospital admissions of hypertension, angina, myocardial infarction, heart disease peaked in winter and early spring when PETs were around 0 degrees C. Admissions had an apparent drop when PETs reached 10 degrees C. More medical resources could have been needed on days when PETs were around 0 degrees C than on other days. While adaptation to such weather change for health professionals and the general public would seem to be imperative, future research with a longitudinal monitoring would still be needed. PMID- 26286806 TI - No age-related decline in efficacy of photodynamic therapy for treatment of basal cell carcinoma. PMID- 26286807 TI - Inhibitory KIR3DL1 alleles are associated with psoriasis. PMID- 26286809 TI - svviz: a read viewer for validating structural variants. AB - Visualizing read alignments is the most effective way to validate candidate structural variants (SVs) with existing data. We present svviz, a sequencing read visualizer for SVs that sorts and displays only reads relevant to a candidate SV. svviz works by searching input bam(s) for potentially relevant reads, realigning them against the inferred sequence of the putative variant allele as well as the reference allele and identifying reads that match one allele better than the other. Separate views of the two alleles are then displayed in a scrollable web browser view, enabling a more intuitive visualization of each allele, compared with the single reference genome-based view common to most current read browsers. The browser view facilitates examining the evidence for or against a putative variant, estimating zygosity, visualizing affected genomic annotations and manual refinement of breakpoints. svviz supports data from most modern sequencing platforms. AVAILABILITY AND IMPLEMENTATION: svviz is implemented in python and freely available from http://svviz.github.io/. PMID- 26286808 TI - An integrated structure- and system-based framework to identify new targets of metabolites and known drugs. AB - MOTIVATION: The inherent promiscuity of small molecules towards protein targets impedes our understanding of healthy versus diseased metabolism. This promiscuity also poses a challenge for the pharmaceutical industry as identifying all protein targets is important to assess (side) effects and repositioning opportunities for a drug. RESULTS: Here, we present a novel integrated structure- and system-based approach of drug-target prediction (iDTP) to enable the large-scale discovery of new targets for small molecules, such as pharmaceutical drugs, co-factors and metabolites (collectively called 'drugs'). For a given drug, our method uses sequence order-independent structure alignment, hierarchical clustering and probabilistic sequence similarity to construct a probabilistic pocket ensemble (PPE) that captures promiscuous structural features of different binding sites on known targets. A drug's PPE is combined with an approximation of its delivery profile to reduce false positives. In our cross-validation study, we use iDTP to predict the known targets of 11 drugs, with 63% sensitivity and 81% specificity. We then predicted novel targets for these drugs-two that are of high pharmacological interest, the peroxisome proliferator-activated receptor gamma and the oncogene B-cell lymphoma 2, were successfully validated through in vitro binding experiments. Our method is broadly applicable for the prediction of protein-small molecule interactions with several novel applications to biological research and drug development. AVAILABILITY AND IMPLEMENTATION: The program, datasets and results are freely available to academic users at http://sfb.kaust.edu.sa/Pages/Software.aspx. PMID- 26286810 TI - GenomeLaser: fast and accurate haplotyping from pedigree genotypes. AB - We present a software tool called GenomeLaser that determines the haplotypes of each person from unphased high-throughput genotypes in family pedigrees. This method features high accuracy, chromosome-range phasing distance, linear computing, flexible pedigree types and flexible genetic marker types. AVAILABILITY AND IMPLEMENTATION: http://www.4dgenome.com/software/genomelaser.html. PMID- 26286811 TI - Epidermolysis bullosa simplex with mottled pigmentation with noncicatricial alopecia: identification of a recurrent p.P25L mutation in KRT5 in four affected family members. PMID- 26286812 TI - Correcting gene expression data when neither the unwanted variation nor the factor of interest are observed. AB - When dealing with large scale gene expression studies, observations are commonly contaminated by sources of unwanted variation such as platforms or batches. Not taking this unwanted variation into account when analyzing the data can lead to spurious associations and to missing important signals. When the analysis is unsupervised, e.g. when the goal is to cluster the samples or to build a corrected version of the dataset--as opposed to the study of an observed factor of interest--taking unwanted variation into account can become a difficult task. The factors driving unwanted variation may be correlated with the unobserved factor of interest, so that correcting for the former can remove the latter if not done carefully. We show how negative control genes and replicate samples can be used to estimate unwanted variation in gene expression, and discuss how this information can be used to correct the expression data. The proposed methods are then evaluated on synthetic data and three gene expression datasets. They generally manage to remove unwanted variation without losing the signal of interest and compare favorably to state-of-the-art corrections. All proposed methods are implemented in the bioconductor package RUVnormalize. PMID- 26286813 TI - Langerhans cell sarcoma following marginal zone lymphoma: expanding the knowledge on mature B cell plasticity. AB - The concept of unidirectional differentiation of the haematopoietic stem cell has been challenged after recent findings that human B cell progenitors and even mature B cells can be reprogrammed into histiocytic/dendritic cells by altering expression of lineage-associated transcription factors. The conversion of mature B cell lymphomas to Langerhans cell neoplasms is not well documented. Three previous reports have described clonally related follicular lymphoma and Langerhans cell tumours, whereas no case has been published of clonally related marginal zone lymphoma and Langerhans cell sarcoma. We describe the case of a 77 year-old patient who developed a Langerhans cell sarcoma and 6 years later a nodal marginal zone lymphoma. Mutation status examination showed 100 % gene identity to the germline sequence, suggesting direct trans-differentiation or dedifferentiation of the nodal marginal zone lymphoma to the Langerhans cell sarcoma rather than a common progenitor. We found inactivation of paired box 5 (PAX-5) in the lymphoma cells by methylation, along with duplication of part of the long arm of chromosomes 16 and 17 in the sarcoma cells. The absence of PAX-5 could have triggered B cells to differentiate into macrophages and dendritic cells. On the other hand, chromosomal imbalances might have activated genes involved in myeloid lineage maturation, transcription activation and oncogenesis. We hypothesize that this occurred because of previous therapies for nodal marginal zone lymphoma. Better understanding of this phenomenon may help in unravelling the molecular interplay between transcription factors during haematopoietic lineage commitment and may expand the spectrum of clonally related mature B cell neoplasms and Langerhans cell tumours. PMID- 26286815 TI - Prevalence of diabetes mellitus in patients with sepsis-triggered Takotsubo syndrome. PMID- 26286814 TI - Validity of non-invasive point-of-care hemoglobin estimation in healthy and sick children-a method comparison study. AB - This study was conducted at a tertiary care center in northern India to evaluate the validity of non-invasive transcutaneous hemoglobin estimation in healthy and sick children in comparison to hemoglobin estimation by traditional lab method. A method comparison study was conducted including 150 subjects. Enrolled patients included 80 neonates with average age of 3.9 +/- 2.1 days, and 70 children with average age of 5.8 +/- 2 years. Each population (newborn and children) comprised of almost equal numbers of healthy and critically ill patients with shock. Hemoglobin (Hb) was estimated on enrolment by transcutaneous spectrophotometry (SpHb) and traditional automated lab analyzer (Hb-Lab). Difference between Hb levels by the two methods (called bias) was measured and analyzed using Bland Altman method. Out of 148 data pairs analyzed, bias between SpHb and Hb-Lab was 1.52 +/- 1.91 g/dl (mean +/- SD). SpHb showed excellent positive correlation with Hb-Lab (r = 0.94 (p < 0.001)) and good visual agreement on Bland-Altman plots. Bias was higher in sick subjects with shock as compared to healthy ones in both neonatal and pediatric population (-2.31 +/- 2.21 g/dl versus -0.77 +/- 1.2 g/dl, respectively). CONCLUSIONS: SpHb showed good accuracy and correlated well with lab estimated Hb levels in healthy children. However, in children with impaired peripheral perfusion, its diagnostic accuracy was inadequate to justify routine use for quantification of severity of anemia and making transfusion decisions solely on non-invasive estimation of hemoglobin. WHAT IS KNOWN: Non-invasive hemoglobin estimation is a relatively new and novel method which has given mixed results regarding its potential efficacy in adults. There is limited data regarding usefulness and accuracy of non-invasive Hb estimation by SpHb in sick neonates and children. WHAT IS NEW: Non-invasive Hb estimation by SpHb monitor is reasonably accurate in healthy neonates and children. It can be used in critically ill children and neonates, but in conjunction with lab confirmation of Hb values. PMID- 26286816 TI - No correlation between body size and hydromorphone analgesia in obese patients in ED. PMID- 26286817 TI - Syncope with QT interval prolongation and T-wave inversion: pulmonary embolism. AB - The patient presented with syncope, without chest pain and dyspnea. There was no peripheral edema or nervous system signs. The electrocardiogram (ECG) showed QT interval prolongation with T-wave inversion in anterior and inferior leads. T wave inversion in the right-sided precordial leads should prompt consideration of right ventricular overload. The patient underwent computed tomography of the chest that demonstrated pulmonary embolism. Ultrasonography of the veins of the lower limbs revealed an isolated calf vein thrombosis. PMID- 26286818 TI - The characteristics of a cohort who tamper with prescribed and diverted opioid medications. AB - AIMS: To describe the methods and baseline characteristics of a cohort of people who tamper with pharmaceutical opioids, formed to examine changes in opioid use following introduction of Reformulated OxyContin(r). METHODS: Participants were 606 people from three Australian jurisdictions who reported past month injecting, snorting, chewing or smoking of a pharmaceutical opioid and had engaged in these practices at least monthly in the past 6 months. Baseline interviews were conducted prior to introduction of Reformulated OxyContin(r) in April 2014. Patterns of opioid use and cohort characteristics were examined according to whether participants were prescribed opioid medications, or exclusively used diverted medication. RESULTS: The cohort reported high levels of moderate/severe depression (61%), moderate/severe anxiety (43%), post-traumatic stress disorder (42%), chronic pain or disability (past 6 months, 54%) and pain (past month, 47%). Lifetime use of oxycodone, morphine, opioid substitution medications and codeine were common. Three-quarters (77%) reported ICD-10 lifetime pharmaceutical opioid dependence and 40% current heroin dependence. Thirteen percent reported past year overdose, and 70% reported at least one past month opioid injection related injury or disease. The cohort displayed complex clinical profiles, but participants currently receiving opioid substitution therapy who were also prescribed other opioids particularly reported a wide range of risk behaviors, despite their health service engagement. CONCLUSIONS: Findings highlight the heterogeneity in the patterns and clinical correlates of opioid use among people who tamper with pharmaceutical opioids. Targeted health interventions are essential to reduce the associated harms. PMID- 26286819 TI - Some Points to Make About an Original Article. PMID- 26286820 TI - Modelling heat conduction in polycrystalline hexagonal boron-nitride films. AB - We conducted extensive molecular dynamics simulations to investigate the thermal conductivity of polycrystalline hexagonal boron-nitride (h-BN) films. To this aim, we constructed large atomistic models of polycrystalline h-BN sheets with random and uniform grain configuration. By performing equilibrium molecular dynamics (EMD) simulations, we investigated the influence of the average grain size on the thermal conductivity of polycrystalline h-BN films at various temperatures. Using the EMD results, we constructed finite element models of polycrystalline h-BN sheets to probe the thermal conductivity of samples with larger grain sizes. Our multiscale investigations not only provide a general viewpoint regarding the heat conduction in h-BN films but also propose that polycrystalline h-BN sheets present high thermal conductivity comparable to monocrystalline sheets. PMID- 26286821 TI - Global variations and time trends in the prevalence of primary open angle glaucoma (POAG): a systematic review and meta-analysis. AB - Systematic review of published population based surveys to examine the relationship between primary open angle glaucoma (POAG) prevalence and demographic factors. A literature search identified population-based studies with quantitative estimates of POAG prevalence (to October 2014). Multilevel binomial logistic regression of log-odds of POAG was used to examine the effect of age and gender among populations of different geographical and ethnic origins, adjusting for study design factors. Eighty-one studies were included (37 countries, 216 214 participants, 5266 POAG cases). Black populations showed highest POAG prevalence, with 5.2% (95% credible interval (CrI) 3.7%, 7.2%) at 60 years, rising to 12.2% (95% CrI 8.9% to 16.6%) at 80 years. Increase in POAG prevalence per decade of age was greatest among Hispanics (2.31, 95% CrI 2.12, 2.52) and White populations (1.99, 95% CrI 1.86, 2.12), and lowest in East and South Asians (1.48, 95% CrI 1.39, 1.57; 1.56, 95% CrI 1.31, 1.88, respectively). Men were more likely to have POAG than women (1.30, 95% CrI 1.22, 1.41). Older studies had lower POAG prevalence, which was related to the inclusion of intraocular pressure in the glaucoma definition. Studies with visual field data on all participants had a higher POAG prevalence than those with visual field data on a subset. Globally 57.5 million people (95% CI 46.4 to 73.1 million) were affected by POAG in 2015, rising to 65.5 million (95% CrI 52.8, 83.2 million) by 2020. This systematic review provides the most precise estimates of POAG prevalence and shows omitting routine visual field assessment in population surveys may have affected case ascertainment. Our findings will be useful to future studies and healthcare planning. PMID- 26286822 TI - Topical cyclosporine A 0.05% for recurrent anterior uveitis. AB - AIM: To evaluate the effectiveness of treatment with cyclosporine A 0.05% eye drops in reducing frequency and severity of recurrences in patients with recurrent anterior uveitis. METHODS: A retrospective case-crossover study was conducted by reviewing medical charts of patients treated for recurrent anterior uveitis between 2002 and 2011 at the Kellogg Eye Center by one cornea specialist. We identified patients who had been treated with topical cyclosporine A 0.05% and recorded data regarding demographics, episodes of anterior uveitis, severity of episodes and treatment modalities before and after initiation of cyclosporine A 0.05%. RESULTS: Eight patients were identified as having been treated with topical cyclosporine 0.05% in addition to standard treatment with an average follow-up of 54.9+/-33.9 months (range: 28-143 months). The patients had statistically significant fewer episodes of anterior uveitis, shorter duration of episodes and fewer total days of inflammation per year while on topical cyclosporine 0.05%. CONCLUSIONS: This study showed improvement of recurrent anterior uveitis in patients while on conventional treatment with cyclosporine A 0.05% compared with conventional treatment alone. PMID- 26286823 TI - Effect of bilateral sequential cataract extraction on intraocular pressure in non glaucomatous Asian eyes. AB - BACKGROUND/AIMS: To determine the effect of cataract extraction on intraocular pressure (IOP) of both eyes in patients undergoing sequential cataract extractions. METHODS: Retrospective review of 116 consecutive treatment-naive non glaucomatous patients who underwent sequential cataract extractions of bilateral eyes. Baseline and postsurgical IOP measurements of eyes after cataract extraction were reviewed. Postsurgical IOP of the first surgical eye was compared with the IOP of the (unoperated) second eye. RESULTS: Before surgery, there was no significant difference between the mean IOP of both eyes (15.4+/-2.6 mm Hg vs 15.2+/-2.5 mm Hg, p=0.22), and good correlation of presurgical IOP in both eyes was observed. After surgery, mean IOP in the first surgical eye decreased to 14.0+/-3.1 mm Hg at 1 month (p<=0.001). There was sustained and statistically significant (p<0.001) decrease in IOP in that eye for 2 years. Mean decrease in IOP ranged from 1.6 (8.6%) to 2.3 mm Hg (14.0%). In contrast, the IOP in the fellow (non-surgical) eye remained unchanged. Subsequently, cataract surgery to the fellow eye resulted in a decrease in IOP to a level similar to that of the previously operated eye, which was similarly sustained. Presurgical IOP was the only factor affecting the magnitude of decrease in IOP. CONCLUSIONS: There is sustained decrease in IOP after cataract extraction in non-glaucomatous eyes. This decrease is of greater magnitude in eyes with higher presurgical IOP and is not affected by the type of surgery performed. The effect of IOP decrease after surgery is unilateral and does not affect the fellow eye. PMID- 26286824 TI - Validation and reliability of the Cardiff Visual Ability Questionnaire for Children using Rasch analysis in a Turkish population. AB - AIM: To develop a Turkish version of the 25-item Cardiff Visual Ability Questionnaire for Children (CVAQC) and to evaluate the validity and reliability of the questionnaire. METHODS: The study involved two main phases. The first phase involved a cross-cultural adaptation of the CVAQC from English into Turkish. The second phase involved the completion of the Turkish version of the CVAQC by 150 partially sighted children (6-18 years old) and validity and reliability checks. Extent and construct validity were investigated using Rasch analysis and reliability by internal consistency and person separation index (PSI). RESULTS: An adequate conceptual equivalence was achieved following the linguistic adaptation process. The dataset for validation comprised 150 participants, 88 (58.7%) of whom were male. Evidence of disordered thresholds was found for one item (item 17). This item was recorded by collapsing two categories and ordered thresholds were evident. All items of the CVAQC were found to fit the Rasch model (chi2 (df)=59.90 (2), p=0.159). The internal construct validity was good (mean item fit (SD) -0.054 (1.132), person fit (SD) -0.629 (2.079)) indicating a single underlying construct. The reliability was good with Cronbach's alpha of 0.91 and PSI of 0.94. Differential item functioning (DIF) was tested for age, sex, diagnosis, degree of visual impairment, and comorbidity. Evidence of DIF was found on age for one item (item 10, reading the board at school). CONCLUSIONS: The Turkish version of the CVAQC is a valid, reliable, and unidimensional questionnaire for partially sighted children aged 6-18 years. TRIAL REGISTRATION NUMBER: Ankara University Ethics Committees registry number 06 177-12. PMID- 26286825 TI - Mathematical abilities in dyslexic children: a diffusion tensor imaging study. AB - Dyslexia is characterized by a deficit in language processing which mainly affects word decoding and spelling skills. In addition, children with dyslexia also show problems in mathematics. However, for the latter, the underlying structural correlates have not been investigated. Sixteen children with dyslexia (mean age 9.8 years [0.39]) and 24 typically developing children (mean age 9.9 years [0.29]) group matched for age, gender, IQ, and handedness underwent 3 T MR diffusion tensor imaging as well as cognitive testing. Tract-Based Spatial Statistics were performed to correlate behavioral data with diffusion data. Children with dyslexia performed worse than controls in standardized verbal number tasks, such as arithmetic efficiency tests (addition, subtraction, multiplication, division). In contrast, the two groups did not differ in the nonverbal number line task. Arithmetic efficiency, representing the total score of the four arithmetic tasks, multiplication, and division, correlated with diffusion measures in widespread areas of the white matter, including bilateral superior and inferior longitudinal fasciculi in children with dyslexia compared to controls. Children with dyslexia demonstrated lower performance in verbal number tasks but performed similarly to controls in a nonverbal number task. Further, an association between verbal arithmetic efficiency and diffusion measures was demonstrated in widespread areas of the white matter suggesting compensatory mechanisms in children with dyslexia compared to controls. Taken together, poor fact retrieval in children with dyslexia is likely a consequence of deficits in the language system, which not only affects literacy skills but also impacts on arithmetic skills. PMID- 26286826 TI - Cortical thinning in former professional soccer players. AB - Soccer is the most popular sport in the world. Soccer players are at high risk for repetitive subconcussive head impact when heading the ball. Whether this leads to long-term alterations of the brain's structure associated with cognitive decline remains unknown. The aim of this study was to evaluate cortical thickness in former professional soccer players using high-resolution structural MR imaging. Fifteen former male professional soccer players (mean age 49.3 [SD 5.1] years) underwent high-resolution structural 3 T MR imaging, as well as cognitive testing. Fifteen male, age-matched former professional non-contact sport athletes (mean age 49.6 [SD 6.4] years) served as controls. Group analyses of cortical thickness were performed using voxel-based statistics. Soccer players demonstrated greater cortical thinning with increasing age compared to controls in the right inferolateral-parietal, temporal, and occipital cortex. Cortical thinning was associated with lower cognitive performance as well as with estimated exposure to repetitive subconcussive head impact. Neurocognitive evaluation revealed decreased memory performance in the soccer players compared to controls. The association of cortical thinning and decreased cognitive performance, as well as exposure to repetitive subconcussive head impact, further supports the hypothesis that repetitive subconcussive head impact may play a role in early cognitive decline in soccer players. Future studies are needed to elucidate the time course of changes in cortical thickness as well as their association with impaired cognitive function and possible underlying neurodegenerative process. PMID- 26286827 TI - Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP ribose). AB - Intrinsically disordered proteins can phase separate from the soluble intracellular space, and tend to aggregate under pathological conditions. The physiological functions and molecular triggers of liquid demixing by phase separation are not well understood. Here we show in vitro and in vivo that the nucleic acid-mimicking biopolymer poly(ADP-ribose) (PAR) nucleates intracellular liquid demixing. PAR levels are markedly induced at sites of DNA damage, and we provide evidence that PAR-seeded liquid demixing results in rapid, yet transient and fully reversible assembly of various intrinsically disordered proteins at DNA break sites. Demixing, which relies on electrostatic interactions between positively charged RGG repeats and negatively charged PAR, is amplified by aggregation-prone prion-like domains, and orchestrates the earliest cellular responses to DNA breakage. We propose that PAR-seeded liquid demixing is a general mechanism to dynamically reorganize the soluble nuclear space with implications for pathological protein aggregation caused by derailed phase separation. PMID- 26286828 TI - Redesigning inpatient care: Testing the effectiveness of an accountable care team model. AB - BACKGROUND: US healthcare underperforms on quality and safety metrics. Inpatient care constitutes an immense opportunity to intervene to improve care. OBJECTIVE: Describe a model of inpatient care and measure its impact. DESIGN: A quantitative assessment of the implementation of a new model of care. The graded implementation of the model allowed us to follow outcomes and measure their association with the dose of the implementation. SETTING AND PATIENTS: Inpatient medical and surgical units in a large academic health center. INTERVENTION: Eight interventions rooted in improving interprofessional collaboration (IPC), enabling data-driven decisions, and providing leadership were implemented. MEASUREMENTS: Outcome data from August 2012 to December 2013 were analyzed using generalized linear mixed models for associations with the implementation of the model. Length of stay (LOS) index, case-mix index-adjusted variable direct costs (CMI-adjusted VDC), 30-day readmission rates, overall patient satisfaction scores, and provider satisfaction with the model were measured. RESULTS: The implementation of the model was associated with decreases in LOS index (P < 0.0001) and CMI-adjusted VDC (P = 0.0006). We did not detect improvements in readmission rates or patient satisfaction scores. Most providers (95.8%, n = 92) agreed that the model had improved the quality and safety of the care delivered. CONCLUSIONS: Creating an environment and framework in which IPC is fostered, performance data are transparently available, and leadership is provided may improve value on both medical and surgical units. These interventions appear to be well accepted by front-line staff. Readmission rates and patient satisfaction remain challenging. PMID- 26286829 TI - Citation Analysis in Bariatric Surgery. PMID- 26286830 TI - Retraction Note to: Correlation between PARP-1 Val762Ala polymorphism and the risk of lung cancer in a Chinese population. PMID- 26286831 TI - A new application of plant virus nanoparticles as drug delivery in breast cancer. AB - Nanoparticles based on non-pathogenic viruses have opened up a novel sector in nanotechnology. Viral nanoparticles based on plant viruses have clear advantages over any synthetic nanoparticles as they are biocompatible and biodegradable self assembled and can be produced inexpensively on a large scale. From several such under-development platforms, only a few have been characterized in the target specific drugs into the cells. Potato virus X is presented as a carrier of the chemotherapeutic drug Herceptin that is currently used as a targeted therapy in (HER2+) breast cancer patients. Here, we used nanoparticles formed from the potato virus X to conjugate the Herceptin (Trastuzumab) monoclonal antibody as a new option in specific targeting of breast cancer. Bioconjugation was performed by EDC/sulfo-N-hydroxysuccinimide (sulfo-NHS) in a two-step protocol. Then, the efficiency of conjugation was investigated by different methods, including sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), Western blot, ELISA, Zetasizer, and transmission electron microscopy. SDS-PAGE and Western blot analysis confirmed an 82-kDa protein band that resulted from conjugation of potato virus X (PVX) coat protein (27 kDa) to heavy chain of Herceptin (55 kDa). Zeta potential values for conjugated particles, PVX, and HER were -7.05, -21.4, and -1.48, respectively. We investigated the efficiency of PVX-Herceptin to induce SK-OV-3 and SK-BR-3 cells (HER2 positive cell lines) apoptosis. We therefore counted cells and measured apoptosis by flow cytometry assay, then compared with Herceptin alone. Based on our data, we confirmed the conjugation of PVX and Herceptin. This study suggests that the PVX-Herceptin conjugates enable Herceptin to become more potential therapeutic tools. PMID- 26286832 TI - Pseudogene integrator complex subunit 6 pseudogene 1 (INTS6P1) as a novel plasma based biomarker for hepatocellular carcinoma screening. AB - In this study, we aimed to determine whether the pseudogene integrator complex subunit 6 pseudogene 1 (INTS6P1) in plasma could be used as a novel approach to screen for and detect hepatocellular carcinoma (HCC). We explored the clinical role of INTS6P1: First, the expression level of INTS6P1 was measured in a cohort of 33 HCC tissue samples and adjacent normal liver tissue, next, the INTS6P1 expression was detected in the culture medium and tumor cells in a cellular experiment, and last, the diagnostic performance of INTS6P1 was examined in an independent cohort of 100 people. The expression level of INTS6P1 was remarkably downregulated in the HCC tissues compared with that in the normal liver tissues (p = 0.0066). In plasma, the INTS6P1 levels were significantly decreased in HCC patients compared with non-HCC patients (p < 0.01). Additionally, we inferred that INTS6P1 might be a prospective biomarker for screening HCC patients in which the serum-AFP levels were lower than 20 ng/ml by the area under the curve receiver operating characteristic (AUC-ROC) analysis (p < 0.05). Pseudogene INTS6P1 could be used as a novel HCC plasma-based biomarker and might improve the accuracy of HCC screening. PMID- 26286833 TI - Src and epidermal growth factor receptor mediate the pro-invasive activity of Bcl w. AB - Members of the Bcl-2 family are established regulators of cell death. However, recent studies have shown that they can also regulate cell migration, invasion, and cancer metastasis. These functions of cancer cells are promoted by pro survival Bcl-2 proteins (Bcl-2, Bcl-XL, and Bcl-w) but are suppressed by pro apoptotic members (Bax and Bak). We have previously shown that Bcl-w and Bcl-XL enhance the ability of respiratory complex-I to produce reactive oxygen species (ROS), stimulating the phosphoinositide 3-kinase (PI3K)-dependent invasion pathway. Here, we show that Bcl-w overexpression increases the phosphorylation of epidermal growth factor receptor (EGFR) and Src, and their interaction. Our results show that ROS production induced by Bcl-w activates Src, which then binds to and phosphorylates EGFR, leading to stimulation of the PI3K-dependent invasion pathway. Importantly, Bcl-w-induced cell invasion was prevented by treating cells with gefitinib (Iressa, ZD1839), an anticancer drug that directly inhibits EGFR. We also show that Bcl-XL can stimulate Src and EGFR phosphorylation, and that this function of Bcl-XL and Bcl-w is antagonized by Bax and Bak. Overall, this study demonstrates the involvement of Src and EGFR in the regulation of cellular invasiveness by Bcl-2 proteins, suggesting that chemotherapeutics targeting EGFR may be useful in preventing the progression of cancers that have altered Bcl-2 protein functions. PMID- 26286834 TI - miR-20a enhances cisplatin resistance of human gastric cancer cell line by targeting NFKBIB. AB - Drug resistance of cancer cells can be regulated by the dysregulated miRNAs, and sustained NFkappaB activation also plays an important role in tumor resistance to chemotherapy. Here, we sought to investigate whether there was a correlation between miR-20a and the NFkappaB pathway to clarify the effects that miR-20a exerted on gastric cancer (GC) chemoresistance. We found that miR-20a was significantly upregulated in GC plasma and tissue samples. In addition, it was upregulated in GC plasma and tissues from patients with cisplatin-resistant gastric cancer cell line SGC7901/cisplatin (DDP). And the upregulation of miR-20a was concurrent with the downregulation of NFKBIB (also known as IkappaBbeta) as well as upregulation of p65, livin, and survivin. The luciferase activity suggested that NFKBIB was the direct target gene of miR-20a. Transfection of miR 20a inhibitor could increase NFKBIB level; downregulate the expression of p65, livin, and survivin; and lead to a higher proportion of apoptotic cells in SGC7901/DDP cells. Conversely, ectopic expression of miR-20a dramatically decreased the expression of NFKBIB; increased the expression of p65, livin, and survivin; and resulted in a decrease in the apoptosis induced by DDP in SGC7901 cells. Taken together, our findings suggested that miR-20a could promote activation of the NFkappaB pathway and downstream targets livin and survivin by targeting NFKBIB, which potentially contributed to GC chemoresistance. PMID- 26286836 TI - Nitrogen Backbone Oligomers. AB - We found that nitrogen and hydrogen directly react at room temperature and pressures of ~35 GPa forming chains of single-bonded nitrogen atom with the rest of the bonds terminated with hydrogen atoms - as identified by IR absorption, Raman, X-ray diffraction experiments and theoretical calculations. At releasing pressures below ~10 GPa, the product transforms into hydrazine. Our findings might open a way for the practical synthesis of these extremely high energetic materials as the formation of nitrogen-hydrogen compounds is favorable already at pressures above 2 GPa according to the calculations. PMID- 26286835 TI - MDR1 polymorphisms have an impact on the prognosis of Chinese diffuse large B cell lymphoma patients. AB - MDR1 (multidrug resistance 1) encodes an adenosine triphosphate (ATP)-dependent efflux transporter that plays a fundamental role in transportation of harmful compounds outside cells to maintain optimal health. The present study was aimed to investigate whether the MDR1 gene single nucleotide polymorphisms (SNPs) were associated with the prognosis of diffuse large B cell lymphoma (DLBCL). Three common SNPs, including C1236T, G2677T/A, and C3435T were focused on, and a total of 150 DLBCL patients from Jiangsu Han population were successively genotyped by polymerase chain reaction-allele-specific primers (PCR-ASP) method or DNA direct sequencing. At locus C1236T, patients carrying T allele (genotype CT and TT) had a prolonged overall survival (OS) when compared with patients with CC genotype (2 year OS 82.6 vs. 60.0 %, respectively; hazard ratio (HR) = 0.1, 95 % confidence interval (CI) 0.01-0.6, p = 0.016). At locus C3435T, complete remission/ complete remission unconfirmed (CR/CRu) rate in C allele group was significantly higher than T allele group (66.7 vs. 51.9 %, respectively; p = 0.009). The progression free survival (PFS) curves of with T (genotype CT and TT) and without T (genotype CC) were significantly different (2-year PFS 46.4 % in with T group vs. 73.7 % in without T group, respectively; HR = 1.9, 95 % CI 1.0-3.6, p = 0.045). At locus G2677T/A, the age for genotypes AG and AT groups was significantly younger than the other genotypes (51.1 +/- 12.6 vs. 57.7 +/- 13.4 years, respectively; p = 0.033). In the haplotype analysis of loci 1236-3435, compared with T-C group, the C-T group displayed an inferior PFS rate (2-year PFS 23.0 vs. 50.6 %, respectively; HR = 7.8, 95 % CI 1.9-32.6, p = 0.005), while C-C and T-T groups showed an intermediate PFS rate. Our findings demonstrate that genotype CT + TT at locus C1236T, allele C, and genotype CC at locus C3435T might contribute to a relatively superior prognosis in DLBCL, as well as haplotype of T-C in loci 1236 3435. Besides, genotypes at locus G2677T/A might affect age at diagnosis, which has important prognostic value for DLBCL. PMID- 26286837 TI - Management strategies for sciatica (PEDro synthesis). PMID- 26286838 TI - Minimum interspatial electrode spacing to optimize air-cathode microbial fuel cell operation with a membrane electrode assembly. AB - An optimum electrode spacing of less than 1cm was determined for an air cathode microbial fuel cell (MFC) with a membrane electrode assembly (MEA) system. The lag period decreased as the electrode spacing increased and the voltage generation increased. Stable power density increased from 93 mW/m(2) to 248 mW/m(2) when the electrode distance increased from 0mm to 9 mm. In the polarization test, a maximum power density (400 mW/m(2)) was obtained at a distance of 6mm. The oxygen mass transfer coefficient (KO=4.60*10(-5) cm/s) with a 0mm spacing was five times higher than that at a 9 mm spacing (0.89*10(-5) cm/s). Long-term operation of the MFC exhibited relatively stable anode potentials of -285+/-25 (0 mm) and -517+/-20 mV (3, 6, and 9 mm) and a gradual decrease in cathode potential for all distances, especially with 0-mm spacing. The performance of air cathode MFCs can be improved using minimum electrode spacing rather than no spacing. PMID- 26286839 TI - Chronic Intermittent Ethanol Exposure Enhances the Excitability and Synaptic Plasticity of Lateral Orbitofrontal Cortex Neurons and Induces a Tolerance to the Acute Inhibitory Actions of Ethanol. AB - Alcoholism is associated with changes in brain reward and control systems, including the prefrontal cortex. In prefrontal areas, the orbitofrontal cortex (OFC) has been suggested to have an important role in the development of alcohol abuse disorders and studies from this laboratory demonstrate that OFC-mediated behaviors are impaired in alcohol-dependent animals. However, it is not known whether chronic alcohol (ethanol) exposure alters the fundamental properties of OFC neurons. In this study, mice were exposed to repeated cycles of chronic intermittent ethanol (CIE) exposure to induce dependence and whole-cell patch clamp electrophysiology was used to examine the effects of CIE treatment on lateral OFC (lOFC) neuron excitability, synaptic transmission, and plasticity. Repeated cycles of CIE exposure and withdrawal enhanced current-evoked action potential (AP) spiking and this was accompanied by a reduction in the after hyperpolarization and a decrease in the functional activity of SK channels. CIE mice also showed an increase in the AMPA/NMDA ratio, and this was associated with an increase in GluA1/GluA2 AMPA receptor expression and a decrease in GluN2B NMDA receptor subunits. Following CIE treatment, lOFC neurons displayed a persistent long-term potentiation of glutamatergic synaptic transmission following a spike timing-dependent protocol. Lastly, CIE treatment diminished the inhibitory effect of acute ethanol on AP spiking of lOFC neurons and reduced expression of the GlyT1 transporter. Taken together, these results suggest that chronic exposure to ethanol leads to enhanced intrinsic excitability and glutamatergic synaptic signaling of lOFC neurons. These alterations may contribute to the impairment of OFC-dependent behaviors in alcohol-dependent individuals. PMID- 26286841 TI - Prostate cancer imaging of FSHR antagonist modified with a hydrophilic linker. AB - Follicle-stimulating hormone receptor (FSHR) is selectively expressed in endothelial cells of prostate cancer (PCa) and becomes a potential target for tumor diagnosis and therapy. (18)F-Al-NOTA-MAL-FSH1 is a promising PET imaging probe for targeting FSHR; however, the unfavorable abdominal backgrounds may hamper clinical translation. GGGRDN is a new hydrophilic linker, which can improve the imaging quality of radiolabeled peptides. In this study, GGGRDN-FSH1 (denoted as FSH2) was designed and conjugated with NOTA-MAL for (18)F-Al radiolabeling. NOTA-MAL-FSH2 was obtained with about 50% yield and labeled using (18)F-Al in a one-step method within 20 min with a yield of 41.46 +/- 10.36% (non decay-corrected). The radiochemical purity was more than 95% and the specific activity was more than 50 GBq/umol. The in vitro stability studies were determined in PBS and human serum. (18)F-Al-NOTA-MAL-FSH2 remained stable in PBS and human serum. Balb/c nude mice bearing PC-3 human PCa were used for in vivo study. PC-3 tumors were clearly visualized with good contrast to background through microPET. ROI analysis showed the tumor uptake values were 2.68 +/- 0.52 and 1.97 +/- 0.61%ID/g at 30 and 60 min post injection (p.i.), respectively. Biodistribution studies showed that the accumulations of (18)F-Al-NOTA-MAL-FSH2 in liver and intestine were 0.47 +/- 0.11 and 0.12 +/- 0.03%ID/g respectively at 60 min p.i. FSHR-binding specificity was also demonstrated by reduced tumor uptake after coinjection of excessive unlabeled FSH2. In conclusion, (18)F-Al NOTA-MAL-FSH2 was successfully prepared in a one-step method and showed better pharmacokinetics than (18) F-Al-NOTA-MAL-FSH1. Favorable preclinical study revealed that (18)F-Al-NOTA-MAL-FSH2 appears to be a promising candidate for FSHR positive tumor imaging. PMID- 26286840 TI - Does Cannabis Cause, Exacerbate or Ameliorate Psychiatric Disorders? An Oversimplified Debate Discussed. AB - There have been extensive policy shifts in the legality of recreational and therapeutic use of cannabis in the United States, as well as a steady increase in the number of people using the drug on a regular basis. Given these rapid societal changes, defining what is known scientifically about the consequences of cannabis use on mental health takes on added public health significance. The purpose of this circumspectives piece is to discuss evidence of cannabis' effects on two psychiatric conditions: post-traumatic stress disorder and psychotic disorders. Dr Haney and Dr Evins will discuss two viewpoints regarding the benefit and harm of cannabis use for these conditions, while outlining what remains unproven and requires further testing to move the field forward. PMID- 26286842 TI - Luminal acetylcholine does not affect the activity of the CFTR in tracheal epithelia of pigs. AB - Fluid homeostasis mediated by the airway epithelium is required for proper lung function, and the CFTR (cystic fibrosis transmembrane conductance regulator) Cl( ) channel is crucial for these processes. Luminal acetylcholine (ACh) acts as an auto-/paracrine mediator to activate Cl(-) channels in airway epithelia and evidence exists showing that nicotinic ACh receptors activate CFTR in murine airway epithelia. The present study investigated whether or not luminal ACh regulates CFTR activity in airway epithelia of pigs, an emerging model for investigations of human airway disease and cystic fibrosis (CF) in particular. Transepithelial ion currents of freshly dissected pig tracheal preparations were measured with Ussing chambers. Application of luminal ACh (100 MUM) induced an increase of the short-circuit current (I(SC)). The ACh effect was mimicked by muscarine and pilocarpine (100 MUM each) and was sensitive to muscarinic receptor antagonists (atropine, 4-DAMP, pirenzepine). No changes of the I(SC) were observed by nicotine (100 MUM) and ACh responses were not affected by nicotine or mecamylamine (25 MUM). Luminal application of IBMX (I, 100 MUM) and forskolin (F, 10 MUM), increase the I(SC) and the I/F-induced current were decreased by the CFTR inhibitor GlyH-101 (GlyH, 50 MUM) indicating increased CFTR activity by I/F. In contrast, GlyH did not affect the ACh-induced current, indicating that the ACh response does not involve the activation of the CFTR. Results from this study suggest that luminal ACh does not regulate the activity of the CFTR in tracheal epithelia of pigs which opposes observation from studies using mice airway epithelium. PMID- 26286844 TI - Prokineticin Receptor Modulators May Potentially Treat Psychiatric and Neurological Disorders. PMID- 26286843 TI - The Relationship of Religiosity, Spirituality, Substance Abuse, and Depression Among Black Men Who Have Sex with Men (MSM). AB - HIV infection rates continue to disproportionately affect Black men who have sex with men (Black MSM) compared to other groups. Research has shown that higher rates of substance use and higher levels of depression are positively correlated with higher sexual risk behavior, and little research has examined relationships between high levels of religiosity and spirituality prevalent in Black culture and issues of substance use and depression among Black MSM. This study did just that and found a relationship between religiosity, spirituality, and risk behavior. These relationships suggest that future HIV prevention models might incorporate religiosity and spirituality to increase the efficacy of risk reduction interventions for Black MSM. PMID- 26286845 TI - Electrostatic interaction map reveals a new binding position for tropomyosin on F actin. AB - Azimuthal movement of tropomyosin around the F-actin thin filament is responsible for muscle activation and relaxation. Recently a model of alphaalpha-tropomyosin, derived from molecular-mechanics and electron microscopy of different contractile states, showed that tropomyosin is rather stiff and pre-bent to present one specific face to F-actin during azimuthal transitions. However, a new model based on cryo-EM of troponin- and myosin-free filaments proposes that the interacting face of tropomyosin can differ significantly from that in the original model. Because resolution was insufficient to assign tropomyosin side-chains, the interacting-face could not be unambiguously determined. Here, we use structural analysis and energy landscapes to further examine the proposed models. The observed bend in seven crystal structures of tropomyosin is much closer in direction and extent to the original model than to the new model. Additionally, we computed the interaction map for repositioning tropomyosin over the F-actin surface, but now extended over a much larger surface than previously (using the original interacting-face). This map shows two energy minima-one corresponding to the "blocked-state" as in the original model, and the other related by a simple 24 A translation of tropomyosin parallel to the F-actin axis. The tropomyosin actin complex defined by the second minimum fits perfectly into the recent cryo EM density, without requiring any change in the interacting-face. Together, these data suggest that movement of tropomyosin between regulatory states does not require interacting-face rotation. Further, they imply that thin filament assembly may involve an interplay between initially seeded tropomyosin molecules growing from distinct binding-site regions on actin. PMID- 26286846 TI - Double-Blind Randomized Clinical Trial of the Efficacy of Venlafaxine Versus Citalopram in the Treatment of the Acute Phase of Major Depressive Disorder. AB - BACKGROUND: There are many antidepressant medications with different side-effects and efficacy profiles. OBJECTIVES: In this study, we compared the efficacy of citalopram and venlafaxine in major depression, which has not yet been studied in Iran. PATIENTS AND METHODS: In this double-blind, randomized controlled trial study, 39 patients aged 18-54 year old with major depressive disorder were randomly allocated into two groups in Yazd City, Iran, between March 2011 and December 2012. A total of 16 patients were treated with velafaxine and 23 patients were treated with citalopram for 8 weeks. Hamilton Depression Rating Scale (HDRS) questionnaire was used for monitoring depression severity. Data were analyzed by SPSS version 20.0 software using Mann Whitney U test and chi-square statistical tests. RESULTS: The HDRS scores were decreased significantly in each group after 8 weeks of treatment (P = 0.001). However, there was no significant difference considering the score of HDRS (P = 0.110). Ten patients in the venlafaxine group and two patients in the citalopram group stopped using medication, all due to nausea or vomiting, or both, and the rate of these two side-effects was significantly higher in the venlafaxine group (P = 0.010). CONCLUSIONS: The efficacy of venlafaxine and citalopram are almost the same, but compliance for the use of medication, such as nausea and vomiting, in patients using venlafaxine is much higher than the citalopram group. Therefore, this implies that citalopram could be a safer antidepressant for patients suffering from major depression. PMID- 26286848 TI - Identification and characterization of VEGF-A-responsive neutrophils expressing CD49d, VEGFR1, and CXCR4 in mice and humans. AB - Vascular endothelial growth factor A (VEGF-A) is upregulated during hypoxia and is the major regulator of angiogenesis. VEGF-A expression has also been found to recruit myeloid cells to ischemic tissues where they contribute to angiogenesis. This study investigates the mechanisms underlying neutrophil recruitment to VEGF A as well as the characteristics of these neutrophils. A previously undefined circulating subset of neutrophils shown to be CD49d(+)VEGFR1(high)CXCR4(high) was identified in mice and humans. By using chimeric mice with impaired VEGF receptor 1 (VEGFR1) or VEGFR2 signaling (Flt-1tk(-/-), tsad(-/-)), we found that parallel activation of VEGFR1 on neutrophils and VEGFR2 on endothelial cells was required for VEGF-A-induced recruitment of circulating neutrophils to tissue. Intravital microscopy of mouse microcirculation revealed that neutrophil recruitment by VEGF A versus by the chemokine macrophage inflammatory protein 2 (MIP-2 [CXCL2]) involved the same steps of the recruitment cascade but that an additional neutrophil integrin (eg, VLA-4 [CD49d/CD29]) played a crucial role in neutrophil crawling and emigration to VEGF-A. Isolated CD49d(+) neutrophils featured increased chemokinesis but not chemotaxis compared with CD49d(-) neutrophils in the presence of VEGF-A. Finally, by targeting the integrin alpha4 subunit (CD49d) in a transplantation-based angiogenesis model that used avascular pancreatic islets transplanted to striated muscle, we demonstrated that inhibiting the recruitment of circulating proangiogenic neutrophils to hypoxic tissue impairs vessel neoformation. Thus, angiogenesis can be modulated by targeting cell surface receptors specifically involved in VEGF-A-dependent recruitment of proangiogenic neutrophils without compromising recruitment of the neutrophil population involved in the immune response to pathogens. PMID- 26286850 TI - Proteasome inhibitors induce FLT3-ITD degradation through autophagy in AML cells. AB - Internal tandem duplication of the Fms-like tyrosine kinase-3 receptor (FLT3) internal tandem duplication (ITD) is found in 30% of acute myeloid leukemia (AML) and is associated with a poor outcome. In addition to tyrosine kinase inhibitors, therapeutic strategies that modulate the expression of FLT3-ITD are also promising. We show that AML samples bearing FLT3-ITD mutations are more sensitive to proteasome inhibitors than wild-type samples and this sensitivity is strongly correlated with a higher FLT3-ITD allelic burden. Using pharmacologic inhibitors of autophagy, specific downregulation of key autophagy proteins including Vps34, autophagy gene (Atg)5, Atg12, Atg13, biochemical, and microscopy studies, we demonstrated that proteasome inhibitors induced cytotoxic autophagy in AML cells. FLT3-ITD molecules were detectable within autophagosomes after bortezomib treatment indicating that autophagy induction was responsible for the early degradation of FLT3-ITD, which preceded the inhibition of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK), PI3K/AKT, and STAT5 pathways, and subsequent activation of cell death. Moreover, proteasome inhibitors overcome resistance to quizartinib induced by mutations in the kinase domain of FLT3, suggesting that these compounds may prevent the emergence of mutant clones arising from tyrosine kinase inhibitor treatments. In xenograft mice models, bortezomib stimulated the conversion of LC3-I to LC3-II, indicating induction of autophagy in vivo, downregulated FLT3-ITD protein expression and improved overall survival. Therefore, selecting patients according to FLT3-ITD mutations could be a new way to detect a significant clinical activity of proteasome inhibitors in AML patients. PMID- 26286849 TI - Genetic diminution of circulating prothrombin ameliorates multiorgan pathologies in sickle cell disease mice. AB - Sickle cell disease (SCD) results in vascular occlusions, chronic hemolytic anemia, and cumulative organ damage. A conspicuous feature of SCD is chronic inflammation and coagulation system activation. Thrombin (factor IIa [FIIa]) is both a central protease in hemostasis and a key modifier of inflammatory processes. To explore the hypothesis that reduced prothrombin (factor II [FII]) levels in SCD will limit vaso-occlusion, vasculopathy, and inflammation, we used 2 strategies to suppress FII in SCD mice. Weekly administration of FII antisense oligonucleotide "gapmer" to Berkeley SCD mice to selectively reduce circulating FII levels to ~10% of normal for 15 weeks significantly diminished early mortality. More comprehensive, long-term comparative studies were done using mice with genetic diminution of circulating FII. Here, cohorts of FII(lox/-) mice (constitutively carrying ~10% normal FII) and FII(WT) mice were tracked in parallel for a year following the imposition of SCD via hematopoietic stem cell transplantation. This genetically imposed suppression of FII levels resulted in an impressive reduction in inflammation (reduction in leukocytosis, thrombocytosis, and circulating interleukin-6 levels), reduced endothelial cell dysfunction (reduced endothelial activation and circulating soluble vascular cell adhesion molecule), and a significant improvement in SCD-associated end-organ damage (nephropathy, pulmonary hypertension, pulmonary inflammation, liver function, inflammatory infiltration, and microinfarctions). Notably, all of these benefits were achieved with a relatively modest 1.25-fold increase in prothrombin times, and in the absence of hemorrhagic complications. Taken together, these data establish that prothrombin is a powerful modifier of SCD-induced end-organ damage, and present a novel therapeutic target to ameliorate SCD pathologies. PMID- 26286847 TI - Mitochondrial DNA maintenance: an appraisal. AB - Mitochondria play a crucial role in a variety of cellular processes ranging from energy metabolism, generation of reactive oxygen species (ROS), and Ca(2+) handling to stress responses, cell survival, and death. Malfunction of the organelle may contribute to the pathogenesis of neuromuscular disorders, cancer, premature aging, and cardiovascular diseases, including myocardial ischemia, cardiomyopathy, and heart failure. Mitochondria are unique as they contain their own genome organized into DNA-protein complexes, so-called mitochondrial nucleoids, along with multiprotein machineries, which promote mitochondrial DNA (mtDNA) replication, transcription, and repair. Although the organelle possesses almost all known nuclear DNA repair pathways, including base excision repair, mismatch repair, and recombinational repair, the proximity of mtDNA to the main sites of ROS production and the lack of protective histones may result in increased susceptibility to oxidative stress and other types of mtDNA damage. Defects in the components of these highly organized machineries, which mediate mtDNA maintenance (replication and repair), may result in accumulation of point mutations and/or deletions in mtDNA and decreased mtDNA copy number impairing mitochondrial function. This review will focus on the mechanisms of mtDNA maintenance with emphasis on the proteins implicated in these processes and their functional role in various disease conditions and aging. PMID- 26286852 TI - Smoke-free legislation in England has reduced stillbirths, neonatal mortality, and low birth weight. PMID- 26286851 TI - Increased CTLA-4(+) T cells and an increased ratio of monocytes with loss of class II (CD14(+) HLA-DR(lo/neg)) found in aggressive pediatric sarcoma patients. AB - BACKGROUND: There is little information regarding the composition of peripheral blood immunity in sarcoma patients and even less in the context of pediatric sarcomas. We describe the immune status using flow cytometry of peripheral blood in patients with osteosarcoma and Ewing sarcoma and demonstrate excessive CD14 in tumor tissues. METHODS: Peripheral blood from patients with OS and ES was collected at diagnosis or relapse, and used for immune phenotyping of 74 different leukocyte phenotypes. Blood from young adult healthy volunteers was collected as controls. Tumor tissues were analyzed by immunohistochemistry. RESULTS: Nineteen patients (average age = 14 y) and 16 controls (average age = 25y) were enrolled on study. Of the 74 phenotypes, 14 were different between sarcoma patients and HV. Sarcoma patients' leukocytes contained a higher percentage of granulocytes (67 % sarcoma vs. 58 % HV; p = 0.003) and fewer lymphocytes (20 % sarcoma vs. 27 % HV; p = 0.001). Increased expression of CTLA-4 was seen in both T cells in sarcoma patients as compared to HV (p = 0.05). Increased CD14(+) HLA-DR(lo/neg) immunosuppressive monocytes were seen in sarcoma patients (p = 0.03); primarily seen in OS. Increased tumor necrosis factor receptor II expression was seen on CD14(+) cells derived from sarcoma patients as compared to HV (p = 0.01). Massive infiltration of CD14(+) cells was seen in OS (>50 % of cells in the majority of tumors) compared to ES (<10-25 % of cells). In contrast, both OS and ES had limited T cell infiltration (generally <10 % of cells). CONCLUSIONS: Pediatric sarcoma patients exhibit several immune phenotypic differences that were exacerbated in more severe disease. These phenotypes have the potential to contribute to immune suppression and may indicate potential targets for immune therapies. PMID- 26286853 TI - In situ allicin generation using targeted alliinase delivery for inhibition of MIA PaCa-2 cells via epigenetic changes, oxidative stress and cyclin-dependent kinase inhibitor (CDKI) expression. AB - Allicin, an extremely active constituent of freshly crushed garlic, is produced upon reaction of substrate alliin with the enzyme alliinase (EC 4.4.1.4). Allicin has been shown to be toxic to several mammalian cells in vitro in a dose dependent manner. In the present study this cytotoxicity was taken to advantage to develop a novel approach to cancer treatment, based on site directed generation of allicin. Alliinase was chemically conjugated to a monoclonal antibody (mAb) which was directed against a specific pancreatic cancer marker, CA19-9. After the CA19-9 mAb-alliinase conjugate was bound to targeted pancreatic cancer cells (MIA PaCa-2 cells), on addition of alliin, the cancer cell-localized alliinase produced allicin, which effectively induced apoptosis in MIA PaCa-2 cells. Specificity of anticancer activity of in situ generated allicin was demonstrated using a novel in vitro system-integrated discrete multiple organ co culture technique. Further, allicin-induced caspase-3 expression, DNA fragmentation, cell cycle arrest, p21(Waf1/Cip1) cyclin-dependent kinase inhibitor expression, ROS generation, GSH depletion, and led to various epigenetic modifications which resulted in stimulation of apoptosis. This approach offers a new therapeutic strategy, wherein alliin and alliinase-bound antibody work together to produce allicin at targeted locations which would reverse gene silencing and suppress cancer cell growth, suggesting that combination of these targeted agents may improve pancreatic cancer therapy. PMID- 26286855 TI - Determining canine skin concentrations of terbinafine to guide the treatment of Malassezia dermatitis. AB - BACKGROUND: Terbinafine (TBF) is known to concentrate and persist in human skin. Its use is increasing in veterinary medicine, but there are limited data concerning its tissue concentration and efficacy in dogs. HYPOTHESIS/OBJECTIVES: (i) Describe TBF accumulation in canine skin; (ii) Integrate pharmacokinetic data with historical minimum inhibitory concentration (MIC) results for Malassezia pachydermatis to verify the currently used dosage of TBF for the treatment of Malassezia dermatitis. ANIMALS: Ten healthy, client-owned dogs. METHODS: Dogs were given TBF (generic preparation, 250 mg tablets) 30 mg/kg per os (p.o.) once daily for 21 days. Serum, sebum and stratum corneum (SC) samples were collected on days 1, 5, 7, 11, 14, 21, 28 and 35. High-pressure liquid chromatography was used to determine drug concentrations in samples. RESULTS: Relevant (mean +/- standard deviation) parameters for TBF in serum, paw SC, thorax SC and sebum, respectively, were: maximum concentration (Cmax , MUg/mL) 23.59 +/- 10.41, 0.31 +/- 0.26, 0.30 +/- 0.32 and 0.48 +/- 0.25; half-life (t1/2 , d) 4.49 +/- 2.24, 6.34 +/- 5.33, 4.64 +/- 3.27 and 5.12 +/- 3.33; time to maximum concentration (Tmax , d) 10.40 +/- 6.98, 13.20 +/- 5.16, 11.90 +/- 8.62 and 10.60 +/- 3.69. CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest that TBF does not achieve high concentrations in canine SC or sebum compared to serum. The mean Cmax of all skin tissues (paw SC, thorax SC and sebum) barely exceeded the reported Malassezia MIC90, of 0.25 MUg/mL, which indicates that doses higher than 30 mg/kg p.o. once daily may be necessary. PMID- 26286854 TI - Morin mitigates acetaminophen-induced liver injury by potentiating Nrf2 regulated survival mechanism through molecular intervention in PHLPP2-Akt-Gsk3beta axis. AB - Acetaminophen (APAP) is frequently taken to relieve pain. Staggered APAP overdoses have been reported to cause acetaminophen-induced liver injury (AILI). Identification of efficacious therapeutic modalities to address complications imposed by accidental/intentional long-term APAP ingestion is needed. Morin, a plant-derived phytochemical, possesses a multitude of pharmacological properties including hepatoprotective action; however, the underlying mechanisms have been inadequately explored. Our present report demonstrates significant attenuation of APAP-mediated liver injury by morin supplementation in vivo as indicated by reduction in histological and serum markers of hepatotoxicity. Morin not only limited necroinflammation as revealed by reduced HMGB1 release, NALP3 and caspase 1 maturation, but also suppressed oxidative stress and mitochondrial dysfunction. This suggests that morin may have exerted its cytoprotective role by way of early intervention in the pathway leading to perpetuation of AILI. Morin reinforced cellular defenses by suppressing Nrf2 ubiquitination and promoting nuclear Nrf2 retention as well as ARE-Nrf2 binding affinity. The effects were observed to be a result of molecular intervention in the activity of PHLPP2, a phosphatase previously reported by us to subdue cellular Nrf2 responses via Fyn kinase activation. Morin was observed to inhibit APAP-induced increase in PHLPP2 activity ex vivo as well as its association with cellular target Akt1. As a result, morin prevented oxidative stress induced deactivation of Akt (Ser473) leading to suppression in GSK3beta and Fyn kinase activation. The study supports the inhibitory action of morin against PHLPP2-regulated Nrf2-suppression and hence indentifies Nrf2-potentiating property of morin that may be exploited in developing novel therapeutic strategy to address AILI. PMID- 26286857 TI - Talking welfare: the importance of a common language. AB - Ontologies describing mouse phenotypes and pathology are well established and becoming more universally used (Smith and Eppig in Mamm Genome 23:653, 2012; Scofield et al. in J Biomed Semant 4:18, 2013). However, the language used to describe and disseminate cage-side observations is less well developed. This article explores the hurdles to unifying a language and terminology, and introduces our initial attempt to do so. PMID- 26286856 TI - Proximal caries lesion detection in primary teeth: does this justify the association of diagnostic methods? AB - The aim of this clinical study was to evaluate and compare the performance of visual exam with use of the Nyvad criteria (visual examination - (VE)), interproximal radiography (BW), laser fluorescence device (DIAGNOdent Pen-DDPen), and their association in the diagnosis of proximal lesions in primary teeth. For this purpose, 45 children (n = 59 surfaces) of both sexes, aged between 5 and 9 years were selected, who presented healthy primary molars or primary molars with signs suggestive of the presence of caries lesions. The surfaces were clinically evaluated and coded according to the Nyvad criteria and immediately afterwards with the DDPen. Radiographic exam was performed only on the surfaces coded with Nyvad scores 2, 3, 5, or 6. Active caries lesions and/or those with discontinuous surfaces were restored, considering the depth of lesion as reference standard. Sensitivity, specificity, accuracy, and area under ROC curve were calculated for each technique and its associations. Visual exam with Nyvad criteria presented the highest specificity, accuracy, and area under ROC curve values. The DDPen presented the highest sensitivity values. Association with one or more methods resulted in an increase in specificity. The performance of visual, radiographic, and DDpen exams and their associations were good; however, the clinical examination with the Nyvad criteria was sufficient for the diagnosis of interproximal lesions in primary teeth. PMID- 26286858 TI - Collaborative Cross and Diversity Outbred data resources in the Mouse Phenome Database. AB - The Mouse Phenome Database was originally conceived as a platform for the integration of phenotype data collected on a defined collection of 40 inbred mouse strains--the "phenome panel." This model provided an impetus for community data sharing, and integration was readily achieved through the reproducible genotypes of the phenome panel strains. Advances in the development of mouse populations lead to an expanded role of the Mouse Phenome Database to encompass new strain panels and inbred strain crosses. The recent introduction of the Collaborative Cross and Diversity Outbred mice, which share an extensive pool of genetic variation from eight founder inbred strains, presents new opportunities and challenges for community data resources. A wide variety of molecular and clinical phenotypes are being collected across genotypes, tissues, ages, environmental exposures, interventions, and treatments. The Mouse Phenome Database provides a framework for retrieval, integration, analysis, and display of these data, enabling them to be evaluated in the context of existing data from standard inbred strains. Primary data in the Mouse Phenome Database are supported by extensive metadata on protocols and procedures. These are centrally curated to ensure accuracy and reproducibility and to provide data in consistent formats. The Mouse Phenome Database represents an established and growing community data resource for mouse phenotype data and encourages submissions from new mouse resources, enabling investigators to integrate existing data into their studies of the phenotypic consequences of genetic variation. PMID- 26286859 TI - Leaf proteome rebalancing in Nicotiana benthamiana for upstream enrichment of a transiently expressed recombinant protein. AB - A key factor influencing the yield of biopharmaceuticals in plants is the ratio of recombinant to host proteins in crude extracts. Postextraction procedures have been devised to enrich recombinant proteins before purification. Here, we assessed the potential of methyl jasmonate (MeJA) as a generic trigger of recombinant protein enrichment in Nicotiana benthamiana leaves before harvesting. Previous studies have reported a significant rebalancing of the leaf proteome via the jasmonate signalling pathway, associated with ribulose 1,5-bisphosphate carboxylase oxygenase (RuBisCO) depletion and the up-regulation of stress-related proteins. As expected, leaf proteome alterations were observed 7 days post-MeJA treatment, associated with lowered RuBisCO pools and the induction of stress inducible proteins such as protease inhibitors, thionins and chitinases. Leaf infiltration with the Agrobacterium tumefaciens bacterial vector 24 h post-MeJA treatment induced a strong accumulation of pathogenesis-related proteins after 6 days, along with a near-complete reversal of MeJA-mediated stress protein up regulation. RuBisCO pools were partly restored upon infiltration, but most of the depletion effect observed in noninfiltrated plants was maintained over six more days, to give crude protein samples with 50% less RuBisCO than untreated tissue. These changes were associated with net levels reaching 425 MUg/g leaf tissue for the blood-typing monoclonal antibody C5-1 expressed in MeJA-treated leaves, compared to less than 200 MUg/g in untreated leaves. Our data confirm overall the ability of MeJA to trigger RuBisCO depletion and recombinant protein enrichment in N. benthamiana leaves, estimated here for C5-1 at more than 2-fold relative to host proteins. PMID- 26286860 TI - Differential diagnosis of leiomyoma in pregnancy: rapid growth, rapid regression and progestogenic effects. PMID- 26286861 TI - Six-dimensional quantum dynamics of dissociative chemisorption of H2 on Co(0001) on an accurate global potential energy surface. AB - Cobalt is a widely used catalyst for many heterogeneous reactions, including the Fischer-Tropsch (FT) process, which converts syngas (H2 and CO) to higher hydrocarbons. As a result, a better understanding of the key chemical steps on the Co surface, such as the dissociative chemisorption of H2 as an initial step of the FT process, is of fundamental importance. Here, we report an accurate full dimensional global potential energy surface for the dissociative chemisorption of H2 on the rigid Co(0001) surface constructed from more than 3000 density functional theory points. The high-fidelity potential energy surface was obtained using the permutation invariant polynomial-neural network method, which preserves both the permutation symmetry of H2 and translational symmetry of the Co(0001) surface. The reaction path features a very low barrier on the top site. Full dimensional quantum dynamical calculations provide insights into the dissociation dynamics and influence of the initial vibrational, rotational, and orientational degrees of freedom. PMID- 26286862 TI - Dielectrophoretic characterization of cells in a stationary nanoliter droplet array with generated chemical gradients. AB - A novel design of reusable microfluidic platform that generates a stationary nanoliter droplet array (SNDA) for cell incubation and analysis, equipped with a complementary array of individually addressable electrodes for each microwell is studied. Various solute concentration gradients were generated between the wells where dielectrophoresis (DEP) was used to characterize the effect of the gradients on the cell's response. The feasibility of generating concentration gradients and observation of DEP responses was demonstrated using a gradient of salts in combination with microparticles and viable cells. L1210 Lymphoma cells were used as the model cells in these experiments. Lymphoma cells' cross-over frequency (COF) decreased with increasing stress conditions. Specifically, a linear decrease in the cell COF was measured as a function of solution tonicity and blebbistatin dose. Lymphoma cells were incubated under a gradient of the chemotherapeutic agent doxorubicin (DOX), which led to saturation in the cell-COF response at 30 nM DOX, demonstrating the potential of the platform in screening of label-free drugs. PMID- 26286863 TI - Early prognosis of metastasis risk in inflammatory breast cancer by texture analysis of tumour microscopic images. AB - Inflammatory breast cancer (IBC) is a rare and aggressive type of locally advanced breast cancer. The purpose of this study was to determine the value of microscopic tumour histomorphology texture for prognosis of local and systemic recurrence at the time of initial IBC diagnosis. This retrospective study included a group of 52 patients selected on the basis of non-metastatic IBC diagnosis, stage IIIB. Gray-Level-Co-Occurrence-Matrix (GLCM) texture analysis was performed on digital images of primary tumour tissue sections stained with haematoxylin/eosin. Obtained values were categorized by use of both data- and outcome-based methods. All five acquired GLCM texture features significantly associated with metastasis outcome. By accuracies of 69-81% and AUCs of 0.71 0.81, prognostic performance of GLCM parameters exceeded that of standard major IBC clinical prognosticators such as tumour grade and response to induction chemotherapy. Furthermore, a composite score consisting of tumour grade, contrast and correlation as independent features resulted in further enhancement of prognostic performance by accuracy of 89%, discrimination efficiency by AUC of 0.93 and an outstanding hazard ratio of 71.6 (95%CI, 41.7-148.4). Internal validation was successfully performed by bootstrap and split-sample cross validation, suggesting that the model is generalizable. This study indicates for the first time the potential use of primary breast tumour histology texture as a highly accurate, simple and cost-effective prognostic indicator of metastasis risk in IBC. Clinical relevance of the obtained results rests on the role of prognosis in decisions on induction chemotherapy and the resulting impact on quality of life and survival. PMID- 26286864 TI - An algorithm for the reduction of genome-scale metabolic network models to meaningful core models. AB - BACKGROUND: Constraint-based analysis of genome-scale metabolic models has become a key methodology to gain insights into functions, capabilities, and properties of cellular metabolism. Since their inception, the size and complexity of genome scale metabolic reconstructions has significantly increased, with a concomitant increase in computational effort required for their analysis. Many stoichiometric methods cannot be applied to large networks comprising several thousand reactions. Furthermore, basic principles of an organism's metabolism can sometimes be easier studied in smaller models focusing on central metabolism. Therefore, an automated and unbiased reduction procedure delivering meaningful core networks from well-curated genome-scale reconstructions is highly desirable. RESULTS: Here we present NetworkReducer, a new algorithm for an automated reduction of metabolic reconstructions to obtain smaller models capturing the central metabolism or other metabolic modules of interest. The algorithm takes as input a network model and a list of protected elements and functions (phenotypes) and applies a pruning step followed by an optional compression step. Network pruning removes elements of the network that are dispensable for the protected functions and delivers a subnetwork of the full system. Loss-free network compression further reduces the network size but not the complexity (dimension) of the solution space. As a proof of concept, we applied NetworkReducer to the iAF1260 genome-scale model of Escherichia coli (2384 reactions, 1669 internal metabolites) to obtain a reduced model that (i) allows the same maximal growth rates under aerobic and anaerobic conditions as in the full model, and (ii) preserves a protected set of reactions representing the central carbon metabolism. The reduced representation comprises 85 metabolites and 105 reactions which we compare to a manually derived E. coli core model. As one particular strength of our approach, NetworkReducer derives a condensed biomass synthesis reaction that is consistent with the full genome-scale model. In a second case study, we reduced a genome-scale model of the cyanobacterium Synechocystis sp. PCC 6803 to obtain a small metabolic module comprising photosynthetic core reactions and the Calvin-Benson cycle allowing synthesis of both biomass and a biofuel (ethanol). CONCLUSION: Although only genome-scale models provide a complete description of an organism's metabolic capabilities, an unbiased stoichiometric reduction of large-scale metabolic models is highly useful. We are confident that the NetworkReducer algorithm provides a valuable tool for the application of computationally expensive analyses, for educational purposes, as well to identify core models for kinetic modeling and isotopic tracer experiments. PMID- 26286865 TI - Molecular dynamics modeling of carbon dioxide, water and natural organic matter in Na-hectorite. AB - Molecular dynamics (MD) modeling of systems containing a Na-exchanged smectite clay (hectorite) and model natural organic matter (NOM) molecules along with pure H2O, pure CO2, or a mixture of H2O and CO2 provides significant new insight into the molecular scale interactions among silicate surfaces, dissolved cations and organic molecules, H2O and CO2 relevant to geological C-sequestration strategies. The simulations for systems containing H2O show the following results; (1) Na(+) does not bridge between NOM molecules and the clay surface at protonation states comparable to near neutral pH conditions. (2) In systems without CO2 the NOM molecules retain charge balancing cations and drift away from the silicate surface. (3) In systems containing both H2O and CO2, the NOM molecules adopt equilibrium positions at the H2O-CO2 interface with the more hydrophilic structural elements facing the H2O and the more hydrophobic ones facing the CO2. In systems with only CO2, NOM and Na(+) ions are pinned to the clay surface with the hydrophilic structural elements of the NOM pointed toward the clay surface. Dynamically, in systems with only CO2, Na(+) diffusion is nearly eliminated, and in systems with a thin water film on the clay surface diffusion perpendicular the surface is greatly reduced relative to the system with bulk water. Energetically, the results for the systems with only H2O show that hydration of the net charge neutral Na-NOM molecule outweighs the sum of its Coulombic and dispersive interactions with the net charge-neutral Na-clay particle and the interactions of the water molecules with the hydrophobic structural elements of the NOM. The aggregation of NOM molecules in solution appears to be driven not by Na(+) bridging between the molecules but by hydrophobic interactions between them. In contrast, for the systems with only CO2 the interaction between the Na-NOM molecules and the CO2 is outweighed by the interaction of NOM with the clay particle. With both H2O and CO2 present, the energetic interactions leading to the hydration of the Na-clay surface and the hydrophilic structural elements of the Na-NOM molecule and the hydrophobic interactions between the CO2 and the hydrophobic aromatic and aliphatic structural elements of the NOM can both be satisfied, leading to the Na-NOM molecules migrating away from the surface and residing at the H2O-CO2 interface. The MD results suggest some alternative explanations for the previously observed (23)Na NMR behavior of Na-hectorite at elevated temperatures and CO2 pressures. PMID- 26286867 TI - LCZ696, The Need for an Indication in Arterial Hypertension. PMID- 26286866 TI - Cumulative Hypoxemia During Sleep Predicts Vascular Endothelial Dysfunction in Patients With Sleep-Disordered Breathing. AB - BACKGROUND: Sleep-disordered breathing (SDB) is associated with repeated intermittent hypoxemia, and it is known as one of the risk factors for cardiovascular diseases. Previous studies assessing the effects of frequency and depth of hypoxemia on cardiovascular diseases have shown conflicting results. The aim of the current study was to clarify what SDB-related parameters most predict endothelial dysfunction to better understand the pathogenesis of endothelial dysfunction in patients with SDB. METHODS: We conducted polysomnography (PSG) and measured flow-mediated vasodilation response (%FMD) in 50 outpatients suspected of SDB. Evaluated indices included: apnea-hypopnea index (AHI), 3% oxygen desaturation index (3%ODI), averaged arterial oxygen saturation (averaged SpO2), lowest arterial oxygen saturation (lowest SpO2), ratio of arterial oxygen saturation <90% (2 cm in size (34.2%) compared with patients with a tear <=2 cm (10.6%) (P < .001). A receiver operating characteristic curve was used to determine the predictive cut-off value for the oldest age and the largest tear size for successful healing, which were calculated as 69 years and 2 cm, respectively, with a specificity of 90%. CONCLUSION: In small to medium-sized rotator cuff tears, grade II fatty degeneration of the infraspinatus muscle according to the Goutallier classification could be a reference point for successful healing, and anatomic outcomes might be better if repair is performed before the patient is 69 years old and the tear size exceeds 2 cm. PMID- 26286880 TI - Clinical and therapeutic factors associated with adverse pathological outcomes in clinically node-negative patients treated with neoadjuvant cisplatin-based chemotherapy and radical cystectomy. AB - PURPOSE: Several disease characteristics have been identified as potential predictors for pathological node involvement (pN+) following radical cystectomy (RC). However, these have not been assessed in patients treated with neoadjuvant chemotherapy (NAC). We endeavored to assess factors predicting adverse pathology in clinically node-negative patients treated with NAC and RC. METHODS: Patients from four North American institutions with cT2-4aN0M0 UC who received three or four cycles of NAC followed by RC were selected. Logistic regression was used to predict pN+, 20% in less than one-tenth of hospitals. CONCLUSIONS: In this large national registry, the use of IABP in the setting of PCI for cardiogenic shock decreased over time without a concurrent increase in O MCS use. The probability of IABP and O-MCS use varied across hospitals, and the use of O-MCS was clustered at a small number of hospitals. PMID- 26286906 TI - Bilateral papilloedema in Camurati-Engelmann disease. AB - A 23-year-old woman presented with bilateral papilloedema in a setting of Camurati-Engelmann disease (CED). She was investigated with neuroimaging showing no optic nerve canal stenosis or jugular vein canal compromise. Her MRI venogram was normal. Her opening pressure at lumbar puncture and serum alkaline phosphatase were raised. Her papilloedema resolved with long-term use of acetazolamide. We believe that our patient suffered from raised intracranial pressure directly as a result of decreasing intracranial volume secondary to CED. PMID- 26286907 TI - A masquerader? Paecilomyces must be distinguished from Penicillium in fungal keratitis: a report of two contrasting cases. AB - We describe the clinical outcomes of two contrasting cases of fungal keratitis due to Paecilomyces spp. The first case involving a 58-year-old woman was complicated by an initial laboratory misidentification as Penicillium and consequently a delay in treatment with an optimised antifungal regimen. The patient had a protracted clinical course that required a total of four penetrating keratoplasties. However, an accurate diagnosis was promptly made in the second case, a 46-year-old woman, which resulted in a satisfactory outcome after penetrating keratoplasty. Our principal aim was to highlight a diagnostic challenge relating to the accurate microbial identification of Paecilomyces spp. This can be difficult given its morphological similarity to Pencillium, and confusion over the two genera has resulted in misdiagnoses reported previously. Our report aims to raise awareness of this potential laboratory misidentification, which can affect clinical decision-making in guiding antimicrobial therapy. PMID- 26286908 TI - Enterobius granulomas as a cause of abdominal pain. PMID- 26286909 TI - Cardiac devices with class 1C antiarrhythmics: a potentially toxic combination. AB - A patient taking regular flecainide for paroxysmal atrial fibrillation presented with broad complex tachycardia and circulatory compromise. With no history of pacemaker insertion and no pacing spikes visible on the ECG, this was presumed to be ventricular tachycardia and treated with electrical cardioversion, leading to p-wave asystole. An indwelling pacemaker was now recognised and ventricular capture was eventually attained by significantly increasing ventricular lead output. Invasive haemodynamic support was required due to new ventricular systolic dysfunction. Pacing thresholds and ventricular function normalised within 72 h consistent with flecainide toxicity; levels were shown to be toxic. Pacemaker interrogation revealed evidence of an undiagnosed atrial flutter, at presentation this was likely slowed by flecainide toxicity to a rate below the pacemaker mode switch, such that it was tracked in the ventricle at the upper tracking rate (120 bpm). Cardioversion terminated the arrhythmia but raised the capture threshold of the ventricle above the maximum lead output. PMID- 26286910 TI - Candy crush: a confounding presentation of blood per rectum in a child. PMID- 26286911 TI - Severe staphylococcal marginal keratitis presenting with hypopyon. PMID- 26286912 TI - Relationship between Complete Pathologic Response to Neoadjuvant Chemotherapy and Survival in Triple-Negative Breast Cancer. AB - PURPOSE: Pathologic complete response (pCR) to neoadjuvant chemotherapy reflects the cytotoxic efficacy of a drug, but patient survival is influenced by many other factors. The purpose of this study was to assess the relationship between increased pCR rate and trial-level survival benefit in triple-negative breast cancer (TNBC). EXPERIMENTAL DESIGN: We used bootstrap resampling from a neoadjuvant trial to simulate trials with different pCR rates. We used estimates from Adjuvant!Online to simulate trial populations with different baseline prognosis and estimated survival improvements associated with changes in pCR rate. RESULTS: Assuming that survival is similar for patients with pCR regardless of treatment arm, a linear relationship exists between increasing pCR rate and increasing recurrence-free survival (RFS). The slope is equal to the difference in survival between those with pCR and residual disease, which in turn is influenced by (i) the baseline prognosis of the trial population, (ii) interactions between prognostic variables and pCR, and (iii) the efficacy of the postneoadjuvant therapies. For example, if the pCR rates are 30% and 60% (OR = 3.5) and the 10-year RFS of the control arm is 0.74, the trial would require 3,550 patients per arm, whereas if the RFS is 0.54, the trial would require only 425 patients per arm to detect significant survival benefit. CONCLUSIONS: We provide a framework for understanding the relationship between pCR and overall survival benefit that can help inform the design of neoadjuvant trials aiming to demonstrate improved survival from a regimen that results in higher pCR rate. PMID- 26286913 TI - SH3BGRL3 Protein as a Potential Prognostic Biomarker for Urothelial Carcinoma: A Novel Binding Partner of Epidermal Growth Factor Receptor. AB - PURPOSE: Mass spectrometry-based biomarker discovery has clinical benefit. To identify novel biomarkers for urothelial carcinoma, we performed quantitative proteomics on pooled urine pairs from patients with and without urothelial carcinoma. EXPERIMENTAL DESIGN: Shot-gun proteomics using liquid chromatography tandem mass spectrometry and stable isotope dimethyl labeling identified 219 candidate proteins. The potential implication of SH3 domain binding glutamic acid rich protein like 3 (SH3BGRL3) was examined by immunoblotting of the urine (n = 13) and urothelial tumors (n = 32). Additional immunohistochemistry was performed on bladder cancer array (n = 1145) and correlated with tumor aggressiveness. Then, biologic functions and signaling pathways of SH3BGRL3 were explored using stable cell lines. RESULTS: The detectable urine SH3BGRL3 in patients with urothelial carcinoma was positively associated with higher histologic grading and muscle invasiveness of urothelial carcinoma. SH3BGRL3 is expressed in 13.9% (159/1145) of bladder cancer cohort and is positively associated with muscle invasion (P = 0.0028). SH3BGRL3 expression is associated with increased risk of progression in patients with nonmuscle-invasive bladder cancer (P = 0.032). SH3BGRL3 expression is significantly associated with a high level of epidermal growth factor receptor (EGFR) in bladder cancer (P < 0.0001). SH3BGRL3 promotes the epithelial-mesenchymal transition, cell migration, and proliferation of urothelial carcinoma in vitro. SH3BGRL3 interacts with phosphor-EGFR at Y1068, Y1086, and Y1173 through Grb2 by its proline-rich motif, and activates the Akt associated signaling pathway. CONCLUSIONS: Evaluation of SH3BGRL3 expression status or urine content may identify a subset of patients with bladder cancer who may require more intensive treatment. SH3BGRL3 deserves further investigation as a cotargeting candidate for designing EGFR-based cancer therapies. Clin Cancer Res; 21(24); 5601-11. (c)2015 AACR. PMID- 26286914 TI - Low Socioeconomic Status, Adverse Gene Expression Profiles, and Clinical Outcomes in Hematopoietic Stem Cell Transplant Recipients. AB - PURPOSE: Low socioeconomic status (SES) is associated with adverse outcomes among unrelated donor hematopoietic stem cell transplant (HCT) recipients, but the biologic mechanisms contributing to this health disparity are poorly understood. Therefore, we examined whether social environment affects expression of a stress related gene expression profile known as the conserved transcriptional response to adversity (CTRA), which involves upregulation of proinflammatory genes and downregulation of genes involved in type I IFN response and antibody synthesis. EXPERIMENTAL DESIGN: We compared pretransplant leukocyte CTRA gene expression between a group of 78 high versus low SES recipients of unrelated donor HCT for acute myelogenous leukemia in first remission. Post hoc exploratory analyses also evaluated whether CTRA gene expression was associated with poor clinical outcomes. RESULTS: Peripheral blood mononuclear cells collected pre-HCT from low SES individuals demonstrated significant CTRA upregulation compared with matched HCT recipients of high SES. Promoter-based bioinformatics implicated distinct patterns of transcription factor activity, including increased CREB signaling and decreased IRF and GR signaling. High expression of the CTRA gene profile was also associated with increased relapse risk and decreased leukemia-free survival. CONCLUSIONS: Low SES is associated with increased expression of the CTRA gene profile, and CTRA gene expression is associated with adverse HCT clinical outcomes. These findings provide a biologic framework within which to understand how social environmental conditions may influence immune function and clinical outcomes in allogeneic HCT. PMID- 26286915 TI - Noninvasive prenatal testing by nanopore sequencing of maternal plasma DNA: feasibility assessment. PMID- 26286916 TI - Stimulus Load and Oscillatory Activity in Higher Cortex. AB - Exploring and exploiting a rich visual environment requires perceiving, attending, and remembering multiple objects simultaneously. Recent studies have suggested that this mental "juggling" of multiple objects may depend on oscillatory neural dynamics. We recorded local field potentials from the lateral intraparietal area, frontal eye fields, and lateral prefrontal cortex while monkeys maintained variable numbers of visual stimuli in working memory. Behavior suggested independent processing of stimuli in each hemifield. During stimulus presentation, higher-frequency power (50-100 Hz) increased with the number of stimuli (load) in the contralateral hemifield, whereas lower-frequency power (8 50 Hz) decreased with the total number of stimuli in both hemifields. During the memory delay, lower-frequency power increased with contralateral load. Load effects on higher frequencies during stimulus encoding and lower frequencies during the memory delay were stronger when neural activity also signaled the location of the stimuli. Like power, higher-frequency synchrony increased with load, but beta synchrony (16-30 Hz) showed the opposite effect, increasing when power decreased (stimulus presentation) and decreasing when power increased (memory delay). Our results suggest roles for lower-frequency oscillations in top down processing and higher-frequency oscillations in bottom-up processing. PMID- 26286917 TI - Multisensory Convergence of Visual and Vestibular Heading Cues in the Pursuit Area of the Frontal Eye Field. AB - Both visual and vestibular sensory cues are important for perceiving one's direction of heading during self-motion. Previous studies have identified multisensory, heading-selective neurons in the dorsal medial superior temporal area (MSTd) and the ventral intraparietal area (VIP). Both MSTd and VIP have strong recurrent connections with the pursuit area of the frontal eye field (FEFsem), but whether FEFsem neurons may contribute to multisensory heading perception remain unknown. We characterized the tuning of macaque FEFsem neurons to visual, vestibular, and multisensory heading stimuli. About two-thirds of FEFsem neurons exhibited significant heading selectivity based on either vestibular or visual stimulation. These multisensory neurons shared many properties, including distributions of tuning strength and heading preferences, with MSTd and VIP neurons. Fisher information analysis also revealed that the average FEFsem neuron was almost as sensitive as MSTd or VIP cells. Visual and vestibular heading preferences in FEFsem tended to be either matched (congruent cells) or discrepant (opposite cells), such that combined stimulation strengthened heading selectivity for congruent cells but weakened heading selectivity for opposite cells. These findings demonstrate that, in addition to oculomotor functions, FEFsem neurons also exhibit properties that may allow them to contribute to a cortical network that processes multisensory heading cues. PMID- 26286918 TI - The Association Between Eye Movements and Cerebellar Activation in a Verbal Working Memory Task. AB - It has been argued that cerebellar activations during cognitive tasks may masquerade as cognition, while actually reflecting processes related to movement planning or motor learning. The present study investigated whether the cerebellar load effect for verbal working memory, that is, increased activations in lobule VI/Crus I and lobule VIIB/VIIIA, is related to eye movements and oculomotor processing. Fifteen participants performed an fMRI-based Sternberg verbal working memory task. Oculomotor and cognitive task demands were manipulated by using closely and widely spaced stimuli, and high and low cognitive load. Trial-based quantitative eye movement parameters were obtained from concurrent eye tracking. Conventional MRI analysis replicated the cerebellar load effect in lobules VI and VIIB/VIIIa. With quantitative eye movement parameters as regressors, analysis yielded very similar activation patterns. While load effect and eye regressor generally recruited spatially distinct neocortical and cerebellar regions, conjunction analysis showed that a small subset of prefrontal areas implicated in the load effect also responded to the eye regressor. The present results indicate that cognitive load-dependent activations in lateral superior and posteroinferior cerebellar regions in the Sternberg task are independent of eye movements occurring during stimulus encoding. This is inconsistent with the notion that cognitive load-dependent cerebellar activations merely reflect oculomotor processing. PMID- 26286919 TI - Smaller Primary Visual Cortex Is Associated with Stronger, but Less Precise Mental Imagery. AB - Despite mental imagery's ubiquitous role in human perception, cognition and behavior, one standout question remains unanswered: Why does imagery vary so much from one individual to the next? Here, we used a behavioral paradigm that measures the functional impact of a mental image on subsequent conscious perception and related these measures to the anatomy of the early visual cortex estimated by fMRI retinotopic mapping. We observed a negative relationship between primary visual cortex (V1) surface area and sensory imagery strength, but found positive relationships between V1 and imagery precision (spatial location and orientation). Hence, individuals with a smaller V1 tended to have stronger, but less precise imagery. In addition, subjective vividness of imagery was positively related to prefrontal cortex volume, but unrelated to V1 anatomy. Our findings present the first evidence for the importance of the V1 layout in shaping the strength of human imagination. PMID- 26286921 TI - Structural Insights into the Incorporation of the Mo Cofactor into Sulfite Oxidase from Site-Directed Spin Labeling. AB - Mononuclear molybdoenzymes catalyze a broad range of redox reactions and are highly conserved in all kingdoms of life. This study addresses the question of how the Mo cofactor (Moco) is incorporated into the apo form of human sulfite oxidase (hSO) by using site-directed spin labeling to determine intramolecular distances in the nanometer range. Comparative measurements of the holo and apo forms of hSO enabled the localization of the corresponding structural changes, which are localized to a short loop (residues 263-273) of the Moco-containing domain. A flap-like movement of the loop provides access to the Moco binding pocket in the apo form of the protein and explains the earlier studies on the in vitro reconstitution of apo-hSO with Moco. Remarkably, the loop motif can be found in a variety of structurally similar molybdoenzymes among various organisms, thus suggesting a common mechanism of Moco incorporation. PMID- 26286920 TI - Psychotic Experiences, Working Memory, and the Developing Brain: A Multimodal Neuroimaging Study. AB - Psychotic experiences (PEs) occur in the general population, especially in children and adolescents, and are associated with poor psychosocial outcomes, impaired cognition, and increased risk of transition to psychosis. It is unknown how the presence and persistence of PEs during early adulthood affects cognition and brain function. The current study assessed working memory as well as brain function and structure in 149 individuals, with and without PEs, drawn from a population cohort. Observer-rated PEs were classified as persistent or transient on the basis of longitudinal assessments. Working memory was assessed using the n back task during fMRI. Dynamic causal modeling (DCM) was used to characterize frontoparietal network configuration and voxel-based morphometry was utilized to examine gray matter. Those with persistent, but not transient, PEs performed worse on the n-back task, compared with controls, yet showed no significant differences in regional brain activation or brain structure. DCM analyses revealed greater emphasis on frontal connectivity within a frontoparietal network in those with PEs compared with controls. We propose that these findings portray an altered configuration of working memory function in the brain, potentially indicative of an adaptive response to atypical development associated with the manifestation of PEs. PMID- 26286922 TI - Missense mutation in SLC4A11 in two Pakistani families affected with congenital hereditary endothelial dystrophy (CHED2). AB - BACKGROUND: Autosomal recessive congenital hereditary endothelial dystrophy (CHED2) is a recessively inherited eye disorder that is more common in consanguineous populations. METHODS: Two families affected with CHED2 were recruited from the Punjab province of Pakistan to identify the underlying genetic defect. Blood samples from both the families, designated as CH01 and CH02, were collected. Genomic DNA was isolated. Initially, linkage analysis using microsatellite markers was carried out to confirm the linkage to the SLC4A11 gene, previously reported to be implicated in the pathology of the disease. Later on, sequencing was carried out to find the pathogenic mutation in the enrolled families. Identified variation was further confirmed by typing 50 ethnically matched normal control samples. RESULTS: The results of linkage analysis indicated the putative linkage to SLAC4A11 gene, located at the CHED2 locus on chromosome 20p13-p12 in both families. Mutational analysis revealed an unidentified homozygous mutation c.2024A>C (p.E675A) in the affected members of both the families. Haplotype analysis of both the families showed that the affected members carry the same haplotype, thereby indicating a possibility of a common ancestral mutation. Use of bioinformatic tools including PolyPhen and SIFT suggested that a single amino acid change of E to A at position 675 affected the function of the protein. CONCLUSION: This study reports a newly identified mutation (c.2024A>C) in the SLC4A11 gene segregating with the diseased haplotype in two consanguineous Pakistani families. PMID- 26286923 TI - A High-Voltage and Ultralong-Life Sodium Full Cell for Stationary Energy Storage. AB - Recently, there has been great interest in developing advanced sodium-ion batteries for large-scale application. Most efforts have concentrated on the search for high-performance electrode materials only in sodium half-cells. Research on sodium full cells for practical application has encountered many problems, such as insufficient cycles with rapid capacity decay, low safety, and low operating voltage. Herein, we present a layered P2-Na0.66 Ni0.17 Co0.17 Ti0.66 O2 , as both an anode (ca. 0.69 V versus Na(+) /Na) and as a high-voltage cathode (ca. 3.74 V versus Na(+) /Na). The full cell based on this bipolar electrode exhibits well-defined voltage plateaus near 3.10 V, which is the highest average voltage in the symmetric cells. It also shows the longest cycle life (75.9 % capacity retention after 1000 cycles) in all sodium full cells, a usable capacity of 92 mAh g(-1) , and superior rate capability (65 mAh g(-1) at a high rate of 2C). PMID- 26286924 TI - Lifetime Risk of Stage 3-5 CKD in a Community-Based Sample in Iceland. AB - BACKGROUND AND OBJECTIVES: Lifetime risk estimates of CKD can be used effectively in public education campaigns. This study sought to estimate lifetime risk of incident CKD stage 3 and higher in Iceland for people without CKD by the age of 45 years. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a prospective cohort study with longitudinal creatinine measurements of residents in Reykjavik, Iceland, from 1967 to 2005. CKD was ascertained by two consecutive eGFR measurements <60 ml/min per 1.73 m(2), development of treated kidney failure, one eGFR<60 ml/min per 1.73 m(2) if the participant died before the next evaluation, or one eGFR<45 ml/min per 1.73 m(2) if it was the last eGFR. RESULTS: Mean follow up was 25 (SD 10) years. Of the study participants, 727 (19%) developed the outcome and 942 (24%) died first. By age 85 years, the lifetime risks for 45-year old women and men without prevalent CKD were 35.8% (95% confidence interval [95% CI], 32.7 to 38.9) and 21.3% (95% CI, 18.7 to 23.8), respectively. Risk was higher in individuals with a lower eGFR, hypertension, and a higher body mass index. Lifetime risk for higher stages of CKD 3b and 4 were less common than stage 3a; by age 85 years, the lifetime risks for CKD stages 3a, 3b, and 4 in women were 38.5% (95% CI, 25.8 to 51.1), 19.4% (95% CI, 8.9 to 29.9), and 3.6% (95% CI, 2.2 to 5.0), respectively. CONCLUSIONS: The lifetime risk of developing CKD stage 3 or higher is substantial, emphasizing the importance of strategies to prevent development of CKD throughout the course of life. Estimates are lower than reported using single estimates of GFR, emphasizing the importance of confirming estimates of reduced GFR in studies of CKD. PMID- 26286925 TI - Understanding the Recent Increase in Ferritin Levels in United States Dialysis Patients: Potential Impact of Changes in Intravenous Iron and Erythropoiesis Stimulating Agent Dosing. AB - BACKGROUND AND OBJECTIVES: Anemia management changed substantially among dialysis patients in the United States around the time of implementation of the new Centers for Medicare & Medicaid Services bundled payment system and erythropoiesis-stimulating agent (ESA) label change in 2011. Among these, average ferritin levels increased dramatically and have remained high since; this study sought to gain understanding of this sustained rise in ferritin levels. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Trends in mean ferritin, hemoglobin, IV iron dose, and ESA dose from 2009 to 2013 were examined in 9735 patients from 91 United States Dialysis Outcomes and Practice Patterns Study facilities. Linear mixed models were used to assess the extent to which intravenous (IV) iron and ESA dose accounted for patients' changes in ferritin over time. RESULTS: Mean ESA dose and hemoglobin levels declined throughout the study. Mean IV iron dose increased from 210 mg/mo in 2009-2010 to a peak of 280 mg/mo in 2011, then declined back to 200 mg/mo and remained stable from 2012 to 2013. Mean ferritin increased from 601 ng/ml in the third quarter of 2009 to 887 ng/ml in the first quarter of 2012; models suggest that higher IV iron dosing was a primary determinant during 2011, but lower ESA doses contributed to the sustained high ferritin levels thereafter. In a subset of 17 facilities that decreased IV iron dose in 2011, mean ferritin rose by 120 ng/ml to 764 ng/ml, which appeared to be primarily due to ESA reduction. Together, changes in IV iron and ESA doses accounted for 46% of the increase in ferritin over the study period. CONCLUSIONS: In contrast to expectations, the rise in average IV iron dose did not persist beyond 2011. The sustained rise in ferritin levels in United States dialysis patients after policy changes in 2011, to average levels well in excess of 800 ng/ml, appeared to be partly due to reductions in ESA dosing and not solely IV iron dosing practices. The effect of these changes in ferritin on health outcomes requires further investigation. PMID- 26286926 TI - Lifetime Risk of CKD: What Does It Really Mean? PMID- 26286927 TI - Late Surgical Bleeding Following Total Artificial Heart Implantation. AB - INTRODUCTION: Mechanical circulatory support for heart failure, including the Total Artificial Heart (TAH, Syncardia, Tucson, AZ, USA) has increased in recent years. This report describes bleeding complications associated with the device. METHODS: A single institution prospectively maintained quality improvement database was reviewed encompassing the first year of clinical experience with the TAH. Patients who underwent TAH implantation were identified, and a review of complications and outcomes was undertaken. RESULTS: Ten patients underwent TAH implant. Four patients experienced delayed postoperative bleeding. In three patients the manifestation of bleeding was tamponade and evidenced by TAH decreased cardiac output. In two patients, at postoperative days 31 and 137, there was a partial disruption of the aortic anastomosis along the outer curvature with pseudoaneurysm formation. Both were repaired by primary suture closure, without use of cardiopulmonary bypass. There was no mortality attributable to bleeding. CONCLUSIONS: TAH patients are at risk for delayed postoperative bleeding, often manifest as an acute decrease in cardiac output. Due to pulsatility and high dP/dT, bleeding from the aortic anastomosis should be considered in the differential of a patient with low flow and/or tamponade. PMID- 26286928 TI - MicRhoDE: a curated database for the analysis of microbial rhodopsin diversity and evolution. AB - Microbial rhodopsins are a diverse group of photoactive transmembrane proteins found in all three domains of life and in viruses. Today, microbial rhodopsin research is a flourishing research field in which new understandings of rhodopsin diversity, function and evolution are contributing to broader microbiological and molecular knowledge. Here, we describe MicRhoDE, a comprehensive, high-quality and freely accessible database that facilitates analysis of the diversity and evolution of microbial rhodopsins. Rhodopsin sequences isolated from a vast array of marine and terrestrial environments were manually collected and curated. To each rhodopsin sequence are associated related metadata, including predicted spectral tuning of the protein, putative activity and function, taxonomy for sequences that can be linked to a 16S rRNA gene, sampling date and location, and supporting literature. The database currently covers 7857 aligned sequences from more than 450 environmental samples or organisms. Based on a robust phylogenetic analysis, we introduce an operational classification system with multiple phylogenetic levels ranging from superclusters to species-level operational taxonomic units. An integrated pipeline for online sequence alignment and phylogenetic tree construction is also provided. With a user-friendly interface and integrated online bioinformatics tools, this unique resource should be highly valuable for upcoming studies of the biogeography, diversity, distribution and evolution of microbial rhodopsins. Database URL: http://micrhode.sb-roscoff.fr. PMID- 26286930 TI - Vascular Pythiosis of the Lower Extremity in Northern Thailand: Ten Years' Experience. AB - Pythiosis is a disease caused by Pythium insidiosum, a fungus-like organism. P. insidiosum is pathogenic in mammals, particularly in horses, dogs, and humans. Human pythiosis can be classified into 4 types: (1) cutaneous/subcutaneous, (2) ocular, (3) vascular, and (4) disseminated pythiosis. Vascular pythiosis is a rare disease but a serious limb- and life-threatening infection. We reviewed 22 cases over a 10-year period in Maharaj Nakorn Chiang Mai/Chiang Mai University Hospital. The survival rate was around 63.6% during our follow-up period. The only effective treatment was complete excision of the infected tissue, which was done mainly by major amputation, such as above-knee amputation. This report raises awareness of this disease, which needs preemptive diagnosis and appropriate treatment. PMID- 26286931 TI - The Buruli Ulcer. AB - Buruli ulcer (BU) is caused by Mycobacterium ulcerans and can manifest as a simple nodule or as aggressive skin ulcers leading to debilitating osteoarthritis or limb deformity. The disease is more prevalent in those living in remote rural areas, especially in children younger than 15 years. The exact mode of transmission is possibly through traumatic skin lesions contaminated by M ulcerans. IS2404 polymerase chain reaction from ulcer swabs or biopsies is a rapid method for confirmation of BU. In coendemic countries, HIV infection complicates the progression of BU, leading to rapidly spreading osteomyelitis. Treatment is principally medical, with antitubercular drugs, and surgery is utilized for complicated disease. Because of ineffective vaccination, primary prevention is the best option for control of the disease. PMID- 26286932 TI - Repairing Pretibial and Foot Soft Tissue Defects with Reverse Transplantation of the Medial Crural Fasciocutaneous Flap. AB - Soft tissue defects of the pretibial area and the foot are among the most common complications in patients with lower extremity injuries and remain a challenge for surgeons. This study examined the clinical effects of repairing pretibial and foot soft tissue defects with a medial crural fasciocutaneous flap. Twenty-three injury cases with soft tissue defects in the middle/lower parts of the tibia and ankle/heel were treated. Of these, 8 injuries were in the lower pretibial region, 11 injuries were in the heel, and 4 injuries were in the dorsalis pedis. The dimensions of the soft tissue defects ranged from 7 cm * 5 cm to 18 cm * 10 cm. The crural fasciocutaneous flap was used for wound repair in all cases. The skin harvest dimensions ranged from 12 cm * 6 cm to 23 cm * 12 cm, and the width of the reverse flap pedicle was greater than 4 cm. The patients were followed up for 6 to 27 months postsurgery. All flaps survived and appeared healthy, and leg function was satisfactorily recovered. Five patients suffered from distal flap necrosis and 2 patients suffered from effusion. The area of the crural fasciocutaneous flap harvest appeared to have a good blood supply, and the procedure was easy to perform without injuries to the main vasculature. In conclusion, the medial crural fasciocutaneous flap is a safe and effective clinical intervention for the reconstruction of soft tissue defects of the pretibial area and foot. PMID- 26286933 TI - Ozone Ameliorates Doxorubicine-Induced Skin Necrosis - results from an animal model. AB - Doxorubicin (DXR) extravasation result with serious morbidity like skin ulceration and necrosis. The purpose of this study is to determine the protective effects of ozone, olive oil, dimethyl sulfoxide (DMSO), and coenzyme Q10 in the treatment of DXR-induced skin ulcers on rats. After an intradermal injection of DXR on a basis of an animal extravasation model, the materials were topically applied. The ulcer sizes were measured, and a punch biopsy was taken from the extravasation site in which the skin ulcers formed at the end of the experiment. The samples were analyzed for tumor necrosis factor alpha (TNF-alpha), interleukin 1-beta (IL1beta), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) enzymes, and examined histopathologically. The ulcer sizes clearly decreased in the study groups, including DMSO, olive oil, ozone plus coenzyme Q10, and ozone plus olive oil groups in comparison with the control group with the exception of the coenzyme Q10 group. The malondialdehyde levels were lower in the DMSO, olive oil, ozone plus olive oil, and ozone plus coenzyme Q10 groups than they were in the control group, but they were not significantly different. The TNF-alpha level was lower in the DMSO, ozone plus olive oil, coenzyme Q10, and ozone plus coenzyme Q10 groups in comparison with the control group. There was no significant change in the SOD, GSH-Px, and IL1beta levels in the study groups in comparison with the control and the sham groups. The ozone plus olive oil group could be considered to be an alternate therapy for skin ulcers due to DXR extravasation. PMID- 26286935 TI - Cryoballoon Ablation for Pulmonary Vein Isolation in Patients With Persistent Atrial Fibrillation: One-Year Outcome Using Second Generation Cryoballoon. AB - BACKGROUND: Data regarding the freedom from atrial fibrillation (AF) in the follow-up of persistent AF patients is limited. The second-generation cryoballoon has better cooling properties compared with first-generation cryoballon. In this study, we aimed to assess the medium-term efficacy of second-generation cryoballoon in patients with persistent AF. METHODS AND RESULTS: A total of 100 patients (63+/-10 years, 80% male) with symptomatic persistent AF, despite >=1 antiarrhythmic drug(s), who were scheduled for pulmonary vein isolation using second-generation cryoballoon were enrolled in this study. Follow-up was based on outpatient clinic visits, including Holter ECGs. Recurrence was defined as a symptomatic or documented arrhythmia episode of >30 seconds excluding a 3-month blanking period. As a result, 393 pulmonary veins (7 patients with common ostium) were successfully isolated. Mean procedural and fluoroscopy times were 96.2+/ 21.3 and 19.7+/-6.7 minutes, respectively. Phrenic nerve palsy occurred in 3% (3/100) of the patients. At a mean follow-up duration of 10.6+/-6.3 months, 67% of the patients were in sinus rhythm. Stepwise multivariable Cox proportional hazard regression analysis showed that early AF recurrence (hazard ratio 3.83, 95% confidence interval 1.91-7.68, P<0.001) was the only independent predictor for late AF recurrence apart from other clinical and echocardiographic variables. CONCLUSIONS: Our findings indicated that second-generation cryoballoon use is associated with favorable outcomes in patients with persistent AF. Recurrence at blanking period was the only predictor of long-term AF recurrence. PMID- 26286936 TI - The Psychometric Properties of the Autobiographical Memory Test in Preschool-Aged Children. AB - The Autobiographical Memory Test (AMT) is the most commonly used tool to assess the phenomenon of overgeneral memory. The AMT has mainly been used in adult populations, but its use in preschool children is less common. The need to create an appropriate instrument to study the memory specificity in preschool years led us to develop an AMT version adapted for early childhood. The AMT-Preschool (AMT P) was administered to a sample of preschool children aged between 3 and 6 (N = 364). The results suggest that the AMT-P functions differently in preschoolers depending on age. With children older than 53 months, results suggest that the AMT-P is appropriate for assessing overgenerality. Nevertheless, with younger children age, the task is more difficult. These results concur with previous research suggesting that the ability to recall specific memories is consolidated from the age of 41/2. PMID- 26286937 TI - Phenotypic Screening for Friedreich Ataxia Using Random shRNA Selection. AB - Friedreich ataxia (FRDA) is an autosomal recessive neuro- and cardio-degenerative disorder for which there are no proven effective treatments. FRDA is caused by decreased expression and/or function of the protein frataxin. Frataxin chaperones iron in the mitochondrial matrix and regulates the iron-sulfur cluster (ISC) assembly complex. ISCs are prosthetic groups critical for the function of the Krebs cycle and the mitochondrial electron transport chain. Decreased expression of frataxin is associated with decreased ISC assembly, mitochondrial iron accumulation, and increased oxidative stress, all of which contribute to mitochondrial dysfunction. In media with beta-hydroxybutyrate (BHB) as carbon source, primary FRDA fibroblasts grow poorly and/or lose viability over several days. We screened a random, short-hairpin-RNA (shRNA)-expressing library in primary FRDA fibroblasts and identified two shRNAs that reverse the growth/viability defect in BHB media. One of these two clones increases frataxin expression in primary FRDA fibroblasts, either as a vector-expressed shRNA or as a transfected short-interfering RNA (siRNA). PMID- 26286938 TI - Low Grade Gliomas in Children. AB - Gliomas represent the most common solid tumor of the nervous system, and can occur as both low and high-grade tumors. Current risk stratification and treatment approaches rely heavily on the morphological classification of gliomas whereby low-grade gliomas have an excellent prognosis, particularly pilocytic astrocytomas, while high-grade gliomas have a poor prognosis. The past decade has witnessed a dramatic increase in scholars' knowledge of the biology of pediatric low-grade gliomas particularly through the advent of integrated genomics and next generation sequencing. Indeed, many of these biological advances are changing treatment paradigms, particularly in low-grade gliomas, where rationale targeted therapies are currently being explored in clinical trials. In this review the authors summarize the current approach to pediatric low grade gliomas and outline the biological advances over the past 10 years, which will be driving the next generation of clinical trials. PMID- 26286939 TI - An interview with Caroline Dean. AB - Caroline Dean is a plant biologist based at the John Innes Centre in Norwich, UK. She helped to establish Arabidopsis as a model plant organism, and has worked for many years on the epigenetic mechanisms that regulate vernalisation, the process by which plants accelerate their flowering after periods of prolonged cold. We met Caroline at the recent Spring Meeting of the British Society for Developmental Biology. We asked her about her career, her thoughts on the plant field and being awarded this year's FEBS EMBO Women in Science Award. PMID- 26286940 TI - The embryo reunited with its membranes in Gottingen. AB - An EMBO workshop entitled 'Embryonic-Extraembryonic Interfaces' took place in Gottingen, Germany, in May 2015. It showcased the enormous breadth of this area not only by touching on the molecular and cellular mechanisms of development, but also because of its coverage of particularly interesting evolutionary questions and of several medically related aspects. This Meeting Review discusses some highlights from the workshop and the emerging themes in the field. PMID- 26286942 TI - The thyroid hormone nuclear receptor TRalpha1 controls the Notch signaling pathway and cell fate in murine intestine. AB - Thyroid hormones control various aspects of gut development and homeostasis. The best-known example is in gastrointestinal tract remodeling during amphibian metamorphosis. It is well documented that these hormones act via the TR nuclear receptors, which are hormone-modulated transcription factors. Several studies have shown that thyroid hormones regulate the expression of several genes in the Notch signaling pathway, indicating a possible means by which they participate in the control of gut physiology. However, the mechanisms and biological significance of this control have remained unexplored. Using multiple in vivo and in vitro approaches, we show that thyroid hormones positively regulate Notch activity through the TRalpha1 receptor. From a molecular point of view, TRalpha1 indirectly controls Notch1, Dll1, Dll4 and Hes1 expression but acts as a direct transcriptional regulator of the Jag1 gene by binding to a responsive element in the Jag1 promoter. Our findings show that the TRalpha1 nuclear receptor plays a key role in intestinal crypt progenitor/stem cell biology by controlling the Notch pathway and hence the balance between cell proliferation and cell differentiation. PMID- 26286943 TI - Intraflagellar transport 27 is essential for hedgehog signaling but dispensable for ciliogenesis during hair follicle morphogenesis. PMID- 26286941 TI - Primordial germ cells: the first cell lineage or the last cells standing? AB - Embryos of many animal models express germ line determinants that suppress transcription and mediate early germ line commitment, which occurs before the somatic cell lineages are established. However, not all animals segregate their germ line in this manner. The 'last cell standing' model describes primordial germ cell (PGC) development in axolotls, in which PGCs are maintained by an extracellular signalling niche, and germ line commitment occurs after gastrulation. Here, we propose that this 'stochastic' mode of PGC specification is conserved in vertebrates, including non-rodent mammals. We postulate that early germ line segregation liberates genetic regulatory networks for somatic development to evolve, and that it therefore emerged repeatedly in the animal kingdom in response to natural selection. PMID- 26286944 TI - Middle East respiratory syndrome (MERS) in Asia: lessons gleaned from the South Korean outbreak. PMID- 26286945 TI - Endemic treponemal diseases. PMID- 26286946 TI - A review of West Nile and Usutu virus co-circulation in Europe: how much do transmission cycles overlap? AB - Due to the increasing global spread of arboviruses, the geographic extent of virus co-circulation is expanding. This complicates the diagnosis of febrile conditions and can have direct effects on the epidemiology. As previously demonstrated, subsequent infections by two closely related viruses, such as those belonging to the Japanese encephalitis virus (JEV) serocomplex, can lead to partial or complete cross-immunity, altering the risk of infections or the outcome of disease. Two flaviviruses that may interact at population level are West Nile virus (WNV) and Usutu virus (USUV). These pathogens have antigenic cross-reactivity and affect human and animal populations throughout Europe. This systematic review investigates the overlap of WNV and USUV transmission cycles, not only geographically but also in terms of host and vector ranges. Co circulation of WNV and USUV was reported in 10 countries and the viruses were found to infect 34 common bird species belonging to 11 orders. Moreover, four mosquito species are potential vectors for both viruses. Taken together, these data suggest that WNV and USUV transmission overlaps substantially in Europe and highlight the importance of further studies investigating the interactions between the two viruses within host and vector populations. PMID- 26286947 TI - Increase of Clostridium perfringens in association with Eimeria in haemorrhagic enteritis in Japanese beef cattle. AB - A coprological survey with detailed clinical observation of naturally occurring haemorrhagic enteritis (HE) cases was conducted to understand the pathophysiology of HE by clarifying the infection status of Eimeria and enteropathogenic bacteria in cattle. Faecal samples from 55 cases of HE and 26 clinically normal animals were collected, and a quantitative examination of Eimeria and potential enteropathogenic bacteria was performed. The number of Eimeria species oocysts per gram of faeces (OPG) exceeded 10,000 in 69.1 per cent of HE cases with a maximum of 1,452,500 OPG and Eimeria zuernii was found to be overwhelmingly dominant. A significant increase in faecal coliform count was observed in HE cases compared with clinically normal animals. Among the animals shedding >10,000 OPG, 42.9 per cent showed a remarkable increase in Clostridium perfringens abundance (>104 CFU/g) in the faeces. In the cases with C. perfringens detected, its abundance was positively correlated with Eimeria OPG and high C. perfringens abundance was always accompanied by high Eimeria OPG. E. zuernii is likely to play a crucial role in massive multiplication of C. perfringens in HE in cattle. PMID- 26286948 TI - Trance-like syndrome in bull terriers. PMID- 26286949 TI - Vertical Ground Reaction Forces are Associated with Pain and Self-Reported Functional Status in Recreational Athletes with Patellofemoral Pain. AB - Individuals with patellofemoral pain (PFP) use different motor strategies during unipodal support in stair climbing activities, which may be assessed by vertical ground reaction force parameters. Thus, the aims of this study were to investigate possible differences in first peak, valley, second peak, and loading rate between recreational female athletes with PFP and pain-free athletes during stair climbing in order to determine the association and prediction capability between these parameters, pain level, and functional status in females with PFP. Thirty-one recreational female athletes with PFP and 31 pain-free recreational female athletes were evaluated with three-dimensional kinetics while performing stair climbing to obtain vertical ground reaction force parameters. A visual analog scale was used to evaluate the usual knee pain. The anterior knee pain scale was used to evaluate knee functional score. First peak and loading rate were associated with pain (r = .46, P = .008; r = .56, P = .001, respectively) and functional limitation (r = .31, P = .049; r = -.36, P = .032, respectively). Forced entry regression revealed the first peak was a significant predictor of pain (36.5%) and functional limitation (28.7%). Our findings suggest that rehabilitation strategies aimed at correcting altered vertical ground reaction force may improve usual knee pain level and self-reported knee function in females with PFP. PMID- 26286950 TI - Photo Quiz: A 76-Year-Old with Community-Acquired Pneumonia. PMID- 26286953 TI - Plasticity of coral physiology under ocean acidification. PMID- 26286954 TI - The joining of the Hsp90 and Hsp70 chaperone cycles yields transient interactions and stable intermediates: insights from mass spectrometry. AB - The Hsp70/Hsp90 chaperone cycles depend on the coordinated interplay of several co-chaperones including Hsp40, Hop and peptidyl-prolyl isomerases such as FKBP52. Because of the many proteins involved in these interactions it is often difficult to delineate all possible combinations of subunits in the complexes formed. We employed mass spectrometry to monitor the assembly and to determine the favoured pathways within these chaperone cycles. Combining the subunit composition with chemical cross-linking and proteomics allowed us to define interaction interfaces, protein dynamics and new intermediates. PMID- 26286957 TI - The Rise and Stall of Canada's Gender-Equity Revolution. AB - The growing symmetry in gender roles is a revolutionary change as consequential as technological advances and globalization. We illustrate how the social world in Canada has changed for women and men over the course of the last century, both in terms of greater gender equity and of policies supporting equity. However, some of the significant changes that occurred in the last 100 years have recently stalled, while the overall progress has been uneven for certain subgroups. We suggest reasons for both the stalling and the unevenness and make policy recommendations for reigniting the march to enhanced equality between the sexes. PMID- 26286955 TI - Exercise-mimetic AICAR transiently benefits brain function. AB - Exercise enhances learning and memory in animals and humans. The role of peripheral factors that may trigger the beneficial effects of running on brain function has been sparsely examined. In particular, it is unknown whether AMP kinase (AMPK) activation in muscle can predict enhancement of brain plasticity. Here we compare the effects of running and administration of AMPK agonist 5 Aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR, 500 mg/kg), for 3, 7 or 14 days in one-month-old male C57BL/6J mice, on muscle AMPK signaling. At the time-points where we observed equivalent running- and AICAR-induced muscle pAMPK levels (7 and 14 days), cell proliferation, synaptic plasticity and gene expression, as well as markers of oxidative stress and inflammation in the dentate gyrus (DG) of the hippocampus and lateral entorhinal cortex (LEC) were evaluated. At the 7-day time-point, both regimens increased new DG cell number and brain-derived neurotrophic factor (BDNF) protein levels. Furthermore, microarray analysis of DG and LEC tissue showed a remarkable overlap between running and AICAR in the regulation of neuronal, mitochondrial and metabolism related gene classes. Interestingly, while similar outcomes for both treatments were stable over time in muscle, in the brain an inversion occurred at fourteen days. The compound no longer increased DG cell proliferation or neurotrophin levels, and upregulated expression of apoptotic genes and inflammatory cytokine interleukin-1beta. Thus, an exercise mimetic that produces changes in muscle consistent with those of exercise does not have the same sustainable positive effects on the brain, indicating that only running consistently benefits brain function. PMID- 26286958 TI - Social Class, Economic Inequality, and the Convergence of Policy Preferences: Evidence from 24 Modern Democracies. AB - Using data from the World Values Survey and national-level indicators for 24 modern democracies, we assess the influence of social class and economic inequality on preferences for government responsibility. We improve on previous research by using multilevel models that account for differences in attitudes both within (i.e., over time) and across countries. Our findings are consistent with the economic self-interest hypothesis. Specifically, working class individuals, who tend to gain the most from government intervention because of their low and often more precarious economic position, are more likely than others to support government intervention. We also find a positive relationship between national-level income inequality and support for government intervention. As income inequality rises, its social ills tend to be more pervasive, resulting in public opinion becoming more supportive of governments taking responsibility for their citizens. We further demonstrate that inequality moderates the relationship between social class and attitudes. Although the effect of income inequality is positive for all social classes, attitudes across social classes become more similar as inequality rises. PMID- 26286956 TI - The effects of graded levels of calorie restriction: III. Impact of short term calorie and protein restriction on mean daily body temperature and torpor use in the C57BL/6 mouse. AB - A commonly observed response in mammals to calorie restriction (CR) is reduced body temperature (Tb). We explored how the Tb of male C57BL/6 mice responded to graded CR (10 to 40%), compared to the response to equivalent levels of protein restriction (PR) over 3 months. Under CR there was a dynamic change in daily Tb over the first 30-35 days, which stabilized thereafter until day 70 after which a further decline was noted. The time to reach stability was dependent on restriction level. Body mass negatively correlated with Tb under ad libitum feeding and positively correlated under CR. The average Tb over the last 20 days was significantly related to the levels of body fat, structural tissue, leptin and insulin-like growth factor-1. Some mice, particularly those under higher levels of CR, showed periods of daily torpor later in the restriction period. None of the changes in Tb under CR were recapitulated by equivalent levels of PR. We conclude that changes in Tb under CR are a response only to the shortfall in calorie intake. The linear relationship between average Tb and the level of restriction supports the idea that Tb changes are an integral aspect of the lifespan effect. PMID- 26286959 TI - Home Care Workers' Skills in the Context of Task Shifting: Complexities in Care Work. AB - Task shifting, which involves the transfer of care work from regulated health care professionals to home care workers (HCWs), is a strategy to ensure the efficient delivery of home care services in Canada and internationally. Using a feminist political economy approach, this paper explores the effects of task shifting on HCWs' skills. Task shifting may be understood as a form of downward substitution-and an effort to increase control over workers while minimizing costs-as some of health-care professionals' responsibilities are divided into simpler tasks and transferred to HCWs. Our interviews with 46 home health-care providers in Ontario, which focused explicitly on HCWs' role in care provision, problematize the belief that "low skilled" care workers have little control over their work. HCWs' skills become more complex when they do transferred tasks, and HCWs sometimes gain greater control over their work. This results in increased autonomy and mastery for many HCWs. In turn, this serves to reinforce the intrinsic rewards of care work, despite the fact that it is low paid and undervalued work. PMID- 26286960 TI - Critical Nexus or Pluralist Discipline? Institutional Ambivalence and the Future of Canadian Sociology. AB - While some scholars believe in a transdisciplinary future for the social sciences and humanities, we argue that sociology would do well to maintain its disciplinary borders, while celebrating the plurality of its intellectual, social, and political content. Although a pluralist position can threaten disciplinary coherence and increase fragmentation, we argue the counterbalance ought to be convergence around shared institutional norms of knowledge production. Establishing these norms is not easy, since there is a great deal of institutional ambivalence at play in the field of sociology. As such, sociology is pushed and pulled between two poles of at least four major continuums of knowledge production, which include the following: (1) interdisciplinary versus discipline-based research; (2) political versus analytical scholarship; (3) professional versus public/policy sociology; and (4) local/national versus global audiences. Since both sides of these ideal-typical continuums contain their own pathologies, we propose adopting a balanced position to correct for the shortcomings of each. Rather than imposing one philosophical or theoretical paradigm for the field, we suggest that embracing the "chaos" of our diverse forms of knowledge and centralizing and integrating findings will serve to strengthen our collective efforts in the long term. PMID- 26286961 TI - Novel chemical library screen identifies naturally occurring plant products that specifically disrupt glioblastoma-endothelial cell interactions. AB - Tumor growth is not solely a consequence of autonomous tumor cell properties. Rather, tumor cells act upon and are acted upon by their microenvironment. It is tumor tissue biology that ultimately determines tumor growth. Thus, we developed a compound library screen for agents that could block essential tumor-promoting effects of the glioblastoma (GBM) perivascular stem cell niche (PVN). We modeled the PVN with three-dimensional primary cultures of human brain microvascular endothelial cells in Matrigel. We previously demonstrated stimulated growth of GBM cells in this PVN model and used this to assay PVN function. We screened the Microsource Spectrum Collection library for drugs that specifically blocked PVN function, without any direct effect on GBM cells themselves. Three candidate PVN disrupting agents, Iridin, Tigogenin and Triacetylresveratrol (TAR), were identified and evaluated in secondary in vitro screens against a panel of primary GBM isolates as well as in two different in vivo intracranial models. Iridin and TAR significantly inhibited intracranial tumor growth and prolonged survival in these mouse models. Together these data identify Iridin and TAR as drugs with novel GBM tissue disrupting effects and validate the importance of preclinical screens designed to address tumor tissue function rather than the mechanisms of autonomous tumor cell growth. PMID- 26286962 TI - Class 3 semaphorins expression and association with innervation and angiogenesis within the degenerate human intervertebral disc. AB - Nerve and blood vessel ingrowth during intervertebral disc degeneration, is thought to be a major cause of low back pain, however the regulation of this process is poorly understood. Here, we investigated the expression and regulation of a subclass of axonal guidance molecules known as the class 3 semaphorins, and their receptors; plexins and neuropilins within human NP tissue and their regulation by pro-inflammatory cytokines. Importantly this determined whether semaphorin expression was associated with the presence of nerves and blood vessels in tissues from human intervertebral discs. The study demonstrated that semaphorin3A, 3C, 3D, 3E and 3F and their receptors were expressed by native NP cells and further demonstrated their expression was regulated by IL-1beta but to a lesser extent by IL-6 and TNFalpha. This is the first study to identify sema3C, sema3D and their receptors within the nucleus pulposus of intervertebral discs. Immunopositivity shows significant increases in semaphorin3C, 3D and their receptor neuropilin-2 in degenerate samples which were shown to contain nerves and blood vessels, compared to non-degenerate samples without nerves and blood vessels. Therefore data presented here suggests that semaphorin3C may have a role in promoting innervation and vascularisation during degeneration, which may go on to cause low back pain. PMID- 26286963 TI - Redox process is crucial for inhibitory properties of aurintricarboxylic acid against activity of YopH: virulence factor of Yersinia pestis. AB - YopH is a bacterial protein tyrosine phosphatase, which is essential for the viability and pathogenic virulence of the plague-causing Yersinia sp. bacteria. Inactivation of YopH activity would lead to the loss of bacterial pathogenicity. We have studied the inhibitory properties of aurintricarboxylic acid (ATA) against YopH phosphatase and found that at nanomolar concentrations ATA reversibly decreases the activity of YopH. Computational docking studies indicated that in all binding poses ATA binds in the YopH active site. Molecular dynamics simulations showed that in the predicted binding pose, ATA binds to the essential Cys403 and Arg409 residues in the active site and has a stronger binding affinity than the natural substrate (pTyr). The cyclic voltammetry experiments suggest that ATA reacts remarkably strongly with molecular oxygen. Additionally, the electrochemical reduction of ATA in the presence of a negative potential from -2.0 to 2.5 V generates a current signal, which is observed for hydrogen peroxide. Here we showed that ATA indicates a unique mechanism of YopH inactivation due to a redox process. We proposed that the potent inhibitory properties of ATA are a result of its strong binding in the YopH active site and in situ generation of hydrogen peroxide near catalytic cysteine residue. PMID- 26286964 TI - Mineral Composition and Nutritive Value of Isotonic and Energy Drinks. AB - Several very popular brands of isotonic and energy drinks consumed for fluid and electrolyte supplementation and stimulation of mental or physical alertness were chosen for investigation. Liquid beverages available in polyethylene bottles and aluminum cans as well as products in the form of tablets and powder in sachets were studied. The total concentrations of 21 elements (Ag, Al, B, Ba, Ca, Cd, Co, Cr, Cu, Fe, Mg, Mn, Mo, Na, Ni, P, Pb, Sr, Ti, V, and Zn), both essential and toxic, were simultaneously determined in preconcentrated drink samples by inductively coupled plasma-optical emission spectrometry (ICP-OES) equipped with pneumatic and ultrasonic nebulizers. Differences between the mineral compositions of isotonic and energy drinks were evaluated and discussed. The highest content of Na was found in both isotonic and energy drinks, whereas quite high concentrations of Mg were found in isotonic drinks, and the highest amount of calcium was quantified in energy drinks. The concentrations of B, Co, Cu, Ni, and P were higher in isotonic drinks, but energy drinks contained greater quantities of Ag, Cr, Zn, Mn, and Mo and toxic elements, as Cd and Pb. A comparison of element contents with micronutrient intake and tolerable levels was performed to evaluate contribution of the investigated beverages to the daily diet. The consumption of 250 cm(3) of an isotonic drink provides from 0.32% (for Mn) up to 14.8% (for Na) of the recommended daily intake. For the energy drinks, the maximum recommended daily intake fulfillment ranged from 0.02% (for V) to 19.4 or 19.8% (for Mg and Na). PMID- 26286965 TI - Sodium Para-aminosalicylic Acid Protected Primary Cultured Basal Ganglia Neurons of Rat from Manganese-Induced Oxidative Impairment and Changes of Amino Acid Neurotransmitters. AB - Manganese (Mn), an essential trace metal for protein synthesis and particularly neurotransmitter metabolism, preferentially accumulates in basal ganglia. However, excessive Mn accumulation may cause neurotoxicity referred to as manganism. Sodium para-aminosalicylic acid (PAS-Na) has been used to treat manganism with unclear molecular mechanisms. Thus, we aim to explore whether PAS Na can inhibit Mn-induced neuronal injury in basal ganglia in vitro. We exposed basal ganglia neurons with 50 MUM manganese chloride (MnCl2) for 24 h and then replaced with 50, 150, and 450 MUM PAS-Na treatment for another 24 h. MnCl2 significantly decreased cell viability but increased leakage rate of lactate dehydrogenase and DNA damage (as shown by increasing percentage of DNA tail and Olive tail moment). Mechanically, Mn reduced glutathione peroxidase and catalase activity and interrupted amino acid neurotransmitter balance. However, PAS-Na treatment reversed the aforementioned Mn-induced toxic effects. Taken together, these results showed that PAS-Na could protect basal ganglia neurons from Mn induced neurotoxicity. PMID- 26286966 TI - CLM29 and CLM24, pyrazolopyrimidine derivatives, have antitumoral activity in vitro in anaplastic thyroid cancer, with or without BRAF mutation. AB - We have studied the antitumor activity of two new "pyrazolo[3,4-d]pyrimidine" compounds (CLM29 and CLM24) that inhibit several targets (including the RET tyrosine kinase, epidermal growth factor receptor, vascular endothelial growth factor receptor, with an antiangiogenic effect) in primary anaplastic thyroid cancer (ATC) cell cultures and in the human cell line 8305C (undifferentiated thyroid cancer). The antitumor effect of CLM29 and CLM24 was tested in: nine primary ATC cultures obtained from patients at the time of surgery at the concentrations of 1, 5, 10, 30, 50 uM; in 8305C cells at 1, 5, 10, 30, 50 uM for CLM29, and 0.001, 0.01, 0.1, 1, 10, 100 uM for CLM24. CLM29, and CLM24 significantly inhibited the proliferation of 8305C cells. A significant reduction of proliferation with CLM29 and CLM24 in ATC cells (P < 0.01, for both, ANOVA) was shown. CLM29 and CLM24 increased the percentage of apoptotic ATC cells dose dependently (P < 0.001, ANOVA). The (V600E) BRAF mutation was observed in three ATCs; the results about the inhibition of proliferation by CLM29 and CLM24, obtained in ATC from tumors with (V600E) BRAF mutation were similar to those from tumors without BRAF mutation. CLM29 inhibited migration and invasion (P < 0.01) of primary ATC cells, while CLM24 had no significant effect. The antitumor activity of two new "pyrazolo[3,4-d]pyrimidine" compounds (CLM24, CLM29) in vitro in ATC, independent from BRAF mutation, has been shown, allowing a future clinical evaluation. PMID- 26286968 TI - The Emotional Intelligence, Health, and Well-Being Nexus: What Have We Learned and What Have We Missed? AB - This paper reviews the claimed pivotal role of emotional intelligence (EI) in well-being and health. Specifically, we examine the utility of EI in predicting health and well-being and point to future research issues that the field might profitably explore. EI is predictive of various indicators of well-being, as well as both physical and psychological health, but existing research has methodological limitations including over-reliance on self-report measures, and neglect of overlap between EI and personality measures. Interventions focusing on emotional perception, understanding and expression, and emotion regulation, seem potentially important for improving health and well-being, but research on EI has not yet made a major contribution to therapeutic practice. Future research, using a finer-grained approach to measurement of both predictors and criteria might most usefully focus on intra- and inter-personal processes that may mediate effects of EI on health. A video abstract of this article can be viewed at http://www.youtube.com/watch?v=2_8JZX1Uc4k. PMID- 26286967 TI - PD-1/PD-L1 signal pathway participates in HCV F protein-induced T cell dysfunction in chronic HCV infection. AB - Programmed cell death-1/programmed cell death-1 ligand 1 (PD-1/PD-L1) inhibitory signal pathway has been verified to be involved in the establishment of persistent viral infections. Blockade of PD-1/PD-L1 engagement to reinvigorate T cell activity is supposed to be a potential therapeutic scheme. Studies have verified the participation of PD-1/PD-L1 in hepatitis C virus (HCV) core protein regulated immune response. To determine the roles of PD-1/PD-L1 signal pathway in HCV F protein-induced immunoreaction in chronic HCV infection, variations in T cells were examined. The results showed that PD-1 expression on CD8(+) and CD4(+) T cells was increased with HCV F stimulation in both chronic HCV patients and healthy controls, and could be reduced partly by PD-1/PD-L1 blocking. Additionally, by PD-1/PD-L1 blocking, HCV F-induced inhibition of T cell proliferation and promotion of cellular apoptosis were partly or even totally recovered. Furthermore, levels of both Th1 and Th2 cytokines were elevated in the presence of anti-PD-L1 antibody. All these results indicated that PD-1/PD-L1 signal pathway also participates in HCV F protein-induced immunoregulation. PD 1/PD-L1 blocking plays important roles in the restoration of effective functionality of the impaired T cells in chronic HCV patients. PMID- 26286969 TI - Life and Job Satisfaction as Predictors of the Incidence of Diabetes. AB - We studied the hypothesised effects of baseline levels of life satisfaction and of job satisfaction on the incidence of diabetes. Participants were 2,305 apparently healthy men and women who underwent routine health checks at two points in time, about 20 months apart. New cases of diabetes (N=104) were defined based on fasting glucose value > 125, or glycosylated hemoglobin value > 6.5, or self-reported physician diagnosis of diabetes and taking medications to treat it. Life satisfaction was measured using the scale constructed by Diener et al. (1985) while job satisfaction was assessed based on the Survey of Working Conditions. In the analyses, we controlled for socio-demographic predictors, for known physiological and behavioral precursors of diabetes, and for depressive symptoms. There was support for our hypothesis that the higher the baseline levels of life satisfaction, the lower the incidence of diabetes. However, job satisfaction did not predict the incidence of diabetes. We obtained the same results when limiting the analysis to new cases of diabetes based on objective criteria only and when using as predictors both life and job satisfaction. We suggest that life satisfaction could be a protective factor reducing the risk of diabetes. PMID- 26286970 TI - The Role of Socioeconomic Status and Control Beliefs on Frequency of Exercise During and After Cardiac Rehabilitation. AB - BACKGROUND: Exercise is considered a key component of rehabilitation for heart patients, yet adherence to exercise remains problematic. This study examined the role of socioeconomic status, patients' perception of control over their heart problem and self-efficacy beliefs on exercise during and after cardiac rehabilitation. METHODS: A prospective design was used. Measures were assessed prior to beginning rehabilitation, at the end of rehabilitation, and 1 month post rehabilitation. RESULTS: There were 107 participants (Mean age = 59 years; 85% men) enrolled in the rehabilitation program who completed the study. Regression analysis showed that initial exercise capacity and patients' perception of control over their heart problem prior to starting rehabilitation predicted exercise during the rehabilitation period. Patients scheduling self-efficacy beliefs at the end of the rehabilitation was the key predictor of exercise 1 month post rehabilitation. CONCLUSIONS: Findings support the role of multiple kinds of control beliefs, including conceptualising self-efficacy in terms of multiple dimensions. Further, there may be different motivational influences on exercise performed during rehabilitation than exercise performed after rehabilitation. PMID- 26286971 TI - A Comparison of Three Job Engagement Measures: Examining their Factorial and Criterion-Related Validity. AB - BACKGROUND: Engagement is an emerging job attitude that purports to measure employees' psychological presence at and involvement in their work. This research compares three academic approaches to engagement, and makes recommendations regarding the most appropriate conceptualisation and measurement of the construct in future research. The current research also investigates whether any of these three approaches to engagement contribute unique variance to the prediction of turnover intentions above and beyond the predictive capacity of alternative constructs. METHODS: An online survey was taken by 382 employees and managers from a mid-sized financial institution. RESULTS: Results failed to support either a multi- or unidimensional factor structure for the Utrecht Work Engagement Scale (UWES) engagement measure. For the Shirom-Melamed Vigor Measure (SMVM), a multi dimensional structure was identified as a good fit, while a unidimensional structure fit poorly. The uni-factorial structure of Britt's engagement measure was confirmed. The Schaufeli measure of engagement was a strong predictor of work outcomes; however, when controlling for job satisfaction and affective commitment, that measure lost its ability to predict intentions to leave. Two components of the Shirom vigor measure held their predictive validity. CONCLUSIONS: Collectively, these findings suggest that the Shirom vigor measure may provide better insight into whether and how much a person is 'into' his or her job. The Schaufeli measure was a good predictor of important work outcomes, but when job satisfaction and affective commitment were controlled, it lost its predictive validity. We were not able to confirm the three-factor structure of the Schaufeli measure. Two components of the Shirom vigor measure predicted turnover intentions after controlling for job satisfaction and affective commitment, suggesting less overlap with those constructs than the Schaufeli measure of engagement. This research adds important information on the nature of engagement and is expected to contribute toward a better understanding of the construct itself, as well as its measurement. PMID- 26286972 TI - Mindfulness and its Role in Physical and Psychological Health. AB - This study examined the relationships of mindfulness, a form of focused self awareness, with physical and psychological health. Mindfulness was measured in terms of four stable forms of awareness: Observe, an awareness of internal and external stimuli; Describe, an ability to verbally express thoughts clearly and easily; Act with Awareness, the tendency to focus on present tasks with undivided attention; and Accept without Judgment, the tendency to take a nonjudgmental attitude toward one's own thoughts and emotions. These aspects of mindfulness were explored in relation to both physical health, which consisted of heart rate variability, a measure of overall cardiovascular health, and psychological health, which consisted of flourishing, existential well-being, negative affect, and social well-being in a sample of 506 undergraduate students. Individuals high in mindfulness showed better cardiovascular health and psychological health. PMID- 26286973 TI - Young Adults' Developmental Task-Related Goals Modify the Association between Self-Focused Goals and Depressive Symptoms. AB - Having self-focused goals is often a risk factor for a higher level of depressive symptoms. The present study investigated whether developmental task-related personal goals could moderate the association between self-focused goals and depressive symptoms in young adulthood. A total of 1,276 Finnish twins aged 21-26 filled out a questionnaire on personal goals. The General Behavior Inventory for depressive symptoms at age 17 and 21-26 was applied. Longitudinal path analyses were carried out. Among those who had a goal related to their own family or life philosophy, self-focused goals were not associated with depressive symptoms, whereas among those who did not express these goals there was a strong association between self-focused goals and higher level of depressive symptoms. Among those who had a goal related to education, the association between self focused goals and depressive symptoms was weaker compared to those who did not express these goals. These results suggest that goals related to one's own family, life philosophy, and education have the potential to decrease the association between self-focused goals and depressive symptoms. PMID- 26286974 TI - Health-Enhancing Physical Activity: Associations with Markers of Well-Being. AB - BACKGROUND: The association between health-enhancing physical activity (HEPA) and well-being was investigated across a cross-sectional (Study 1; N=243) and a longitudinal, two-wave (Study 2; N=198) design. Study 2 further examined the role played by fulfilling basic psychological needs in terms of understanding the mechanisms via which HEPA is associated with well-being. METHODS: Women enrolled in undergraduate courses were surveyed. RESULTS: In general, greater HEPA was associated with greater well-being (Study 1; rs ranged from .03 to .25). Change score analyses revealed that increased HEPA positively predicted well-being (Study 2; R(2) adj=0.03 to 0.15) with psychological need fulfilment underpinning this relationship. CONCLUSIONS: Collectively these findings indicate that increased engagement in health-enhancing physical activity represents one factor associated with greater well-being. Continued investigation of basic psychological need fulfilment as one mechanism underpinning the HEPA-well-being relationship appears justified. PMID- 26286975 TI - Emotional Intelligence Relates to Well-Being: Evidence from the Situational Judgment Test of Emotional Management. AB - BACKGROUND: This research was conducted to examine whether people high in emotional intelligence (EI) have greater well-being than people low in EI. METHOD: The Situational Test of Emotion Management, Scales of Psychological Well being, and Day Reconstruction Method were completed by 131 college students. RESULTS: Responses to the Situational Test of Emotion Management were strongly related to eudaimonic well-being as measured by responses on the Scales of Psychological Well-being (r=.54). Furthermore, the ability to manage emotions was related to hedonic well-being, correlating with both the frequency of experienced positive affect and the frequency of experienced negative affect, as measured by the Day Reconstruction Method. CONCLUSION: Two aspects of these results suggest a relationship between EI and well-being. First, the observed relationship between ability EI and psychological well-being is the largest reported in the literature to date. Second, this study is the first use of the Day Reconstruction Method to examine the relationship between well-being and EI. Results are discussed in terms of the potential for training emotion management to enhance well-being. Methodological advances for future research are also suggested. PMID- 26286976 TI - The Basic Psychological Needs at Work Scale: Measurement Invariance between Canada and France. AB - The purpose of this study is to develop and validate the Basic Psychological Needs at Work Scale (BPNWS) in French, but items are also provided in English in the article. The BPNWS is a work-related self-report instrument designed to measure the degree to which the needs for autonomy, competence, and relatedness, as identified by Self-Determination Theory (Deci & Ryan, 2000), are satisfied at work. Using exploratory and confirmatory factor analysis, the first study examines the structure of the BPNWS in a group of 271 workers. The second study tests the measurement invariance of the scale in a group of 851 teachers from two different cultures, Canada and France. Results support the three-factor structure and show adequate internal consistency, as well as nomological validity across samples. PMID- 26286977 TI - An Experimental Test of Women's Body Dissatisfaction Reduction through Self Affirmation. AB - BACKGROUND: Body dissatisfaction (BD)--a health concern in its own right-often is positioned early in the causal chain toward eating pathology, and is a practical point of intervention for those aiming to reduce its negative health consequences. One approach to reducing people's resistance to receipt of other unwanted health information (e.g. about smoking) has been through the application of self-affirmation theory. This theory asserts that the self needs to maintain its integrity and, as such, when incoming information is threatening, one's defensive shields are activated and it is deflected. One way to reduce defensiveness, however, is to bolster some other aspect of the self. METHOD: We applied a one-shot, self-affirmation-based manipulation via a randomised controlled design (N=86) to a group of body-dissatisfied college women and compared its effects to a control group. RESULTS: All hypotheses predicted by self-affirmation theory were supported: Women who were self-affirmed exhibited (a) greater openness to threatening information about the dangers of BD, (b) lower BD, and (c) greater intention to reduce criticism of their bodies. CONCLUSIONS: The present study provided an experimental test of a mechanism of action which might prove useful in a comprehensive intervention program. PMID- 26286978 TI - Assessment of Parent Orientation towards Autonomy vs. Control in Promoting Children's Healthy Eating and Exercise. AB - BACKGROUND: Self-determination theory has been widely applied to understanding individuals' health-related behaviors such as eating healthy foods and exercising. Different reasons for engagement are associated with varying levels of personal agency or autonomy. Authority figures in the environment can be supportive of autonomy or, in contrast, controlling. Although researchers have assessed individuals' perceptions of the autonomy-support in their environments, studies have not directly examined the authority figures' orientations to autonomy with respect to health contexts. METHODS: A new scale, Parent Orientations to Health, was created to investigate parent orientation to autonomy and control with respect to healthy eating and exercise in children. One hundred and forty-three parents of elementary school-aged children responded to the scale. RESULTS: Scale validation and reliability results indicate that the scale successfully assessed parent orientation towards autonomy for children in health contexts. Furthermore, parent autonomy orientation varied according to child weight status and the healthiness of the child's diet. CONCLUSIONS: Parent orientation towards autonomy can be evaluated through the use of the Parent Orientations to Health scale. In addition, parent autonomy orientation is associated with both the healthiness of the child's diet (as perceived by the parent) and the child's body mass index. PMID- 26286979 TI - Are only Emotional Strengths Emotional? Character Strengths and Disposition to Positive Emotions. AB - This study aimed to examine the relations between character strengths and dispositional positive emotions (i.e. joy, contentment, pride, love, compassion, amusement, and awe). A sample of 574 German-speaking adults filled in the Dispositional Positive Emotion Scales (DPES; Shiota, Keltner, & John, 2006), and the Values in Action Inventory of Strengths (VIA-IS; Peterson, Park, & Seligman, 2005). The factorial structure of the DPES was examined on item level. Joy and contentment could not be clearly separated; the items of the other five emotions loaded on separate factors. A confirmatory factor analysis assuming two latent factors (self-oriented and object/situation specific) was computed on scale level. Results confirmed the existence of these factors, but also indicated that the seven emotions did not split up into two clearly separable families. Correlations between dispositional positive emotions and character strengths were positive and generally low to moderate; a few theoretically meaningful strengths emotions pairs yielded coefficients>.40. Finally, the link between five character strengths factors (i.e. emotional strengths, interpersonal strengths, strengths of restraint, intellectual strengths, and theological strengths) and the emotional dispositions was examined. Each of the factors displayed a distinctive "emotional pattern"; emotional strengths evidenced the most numerous and strongest links to emotional dispositions. PMID- 26286980 TI - Awareness of the Historical Role of the Church and Change in Self-Esteem among Older African Americans. AB - The purpose of this study is to see if greater awareness of the historical role of the church in the black community is associated with a greater sense of self worth among older African Americans. A latent variable model is evaluated that contains the following core hypotheses: (1) older blacks who go to church more often will receive more spiritual support (i.e. encouragement to adopt religious teachings and beliefs) from fellow church members; (2) greater spiritual support is associated with greater awareness of the role that has been played by the church in the black community; and (3) greater awareness of the historical role of the church is associated with a greater sense of self-worth. Findings from a nationwide survey of older African Americans provide support for each of these linkages. Greater confidence may be placed in the findings because they are based on data that have been gathered at more than one point in time. PMID- 26286981 TI - News Feature: Intimate partnerships. PMID- 26286983 TI - Reproduction, symbiosis, and the eukaryotic cell. AB - This paper develops a conceptual framework for addressing questions about reproduction, individuality, and the units of selection in symbiotic associations, with special attention to the origin of the eukaryotic cell. Three kinds of reproduction are distinguished, and a possible evolutionary sequence giving rise to a mitochondrion-containing eukaryotic cell from an endosymbiotic partnership is analyzed as a series of transitions between each of the three forms of reproduction. The sequence of changes seen in this "egalitarian" evolutionary transition is compared with those that apply in "fraternal" transitions, such as the evolution of multicellularity in animals. PMID- 26286984 TI - Genome expansion via lineage splitting and genome reduction in the cicada endosymbiont Hodgkinia. AB - Comparative genomics from mitochondria, plastids, and mutualistic endosymbiotic bacteria has shown that the stable establishment of a bacterium in a host cell results in genome reduction. Although many highly reduced genomes from endosymbiotic bacteria are stable in gene content and genome structure, organelle genomes are sometimes characterized by dramatic structural diversity. Previous results from Candidatus Hodgkinia cicadicola, an endosymbiont of cicadas, revealed that some lineages of this bacterium had split into two new cytologically distinct yet genetically interdependent species. It was hypothesized that the long life cycle of cicadas in part enabled this unusual lineage-splitting event. Here we test this hypothesis by investigating the structure of the Ca. Hodgkinia genome in one of the longest-lived cicadas, Magicicada tredecim. We show that the Ca. Hodgkinia genome from M. tredecim has fragmented into multiple new chromosomes or genomes, with at least some remaining partitioned into discrete cells. We also show that this lineage-splitting process has resulted in a complex of Ca. Hodgkinia genomes that are 1.1-Mb pairs in length when considered together, an almost 10-fold increase in size from the hypothetical single-genome ancestor. These results parallel some examples of genome fragmentation and expansion in organelles, although the mechanisms that give rise to these extreme genome instabilities are likely different. PMID- 26286985 TI - Why chloroplasts and mitochondria retain their own genomes and genetic systems: Colocation for redox regulation of gene expression. AB - Chloroplasts and mitochondria are subcellular bioenergetic organelles with their own genomes and genetic systems. DNA replication and transmission to daughter organelles produces cytoplasmic inheritance of characters associated with primary events in photosynthesis and respiration. The prokaryotic ancestors of chloroplasts and mitochondria were endosymbionts whose genes became copied to the genomes of their cellular hosts. These copies gave rise to nuclear chromosomal genes that encode cytosolic proteins and precursor proteins that are synthesized in the cytosol for import into the organelle into which the endosymbiont evolved. What accounts for the retention of genes for the complete synthesis within chloroplasts and mitochondria of a tiny minority of their protein subunits? One hypothesis is that expression of genes for protein subunits of energy-transducing enzymes must respond to physical environmental change by means of a direct and unconditional regulatory control--control exerted by change in the redox state of the corresponding gene product. This hypothesis proposes that, to preserve function, an entire redox regulatory system has to be retained within its original membrane-bound compartment. Colocation of gene and gene product for redox regulation of gene expression (CoRR) is a hypothesis in agreement with the results of a variety of experiments designed to test it and which seem to have no other satisfactory explanation. Here, I review evidence relating to CoRR and discuss its development, conclusions, and implications. This overview also identifies predictions concerning the results of experiments that may yet prove the hypothesis to be incorrect. PMID- 26286986 TI - Propagation of prions causing synucleinopathies in cultured cells. AB - Increasingly, evidence argues that many neurodegenerative diseases, including progressive supranuclear palsy (PSP), are caused by prions, which are alternatively folded proteins undergoing self-propagation. In earlier studies, PSP prions were detected by infecting human embryonic kidney (HEK) cells expressing a tau fragment [TauRD(LM)] fused to yellow fluorescent protein (YFP). Here, we report on an improved bioassay using selective precipitation of tau prions from human PSP brain homogenates before infection of the HEK cells. Tau prions were measured by counting the number of cells with TauRD(LM)-YFP aggregates using confocal fluorescence microscopy. In parallel studies, we fused alpha-synuclein to YFP to bioassay alpha-synuclein prions in the brains of patients who died of multiple system atrophy (MSA). Previously, MSA prion detection required ~120 d for transmission into transgenic mice, whereas our cultured cell assay needed only 4 d. Variation in MSA prion levels in four different brain regions from three patients provided evidence for three different MSA prion strains. Attempts to demonstrate alpha-synuclein prions in brain homogenates from Parkinson's disease patients were unsuccessful, identifying an important biological difference between the two synucleinopathies. Partial purification of tau and alpha-synuclein prions facilitated measuring the levels of these protein pathogens in human brains. Our studies should facilitate investigations of the pathogenesis of both tau and alpha-synuclein prion disorders as well as help decipher the basic biology of those prions that attack the CNS. PMID- 26286987 TI - Phylogenetic analyses of melanoma reveal complex patterns of metastatic dissemination. AB - Melanoma is difficult to treat once it becomes metastatic. However, the precise ancestral relationship between primary tumors and their metastases is not well understood. We performed whole-exome sequencing of primary melanomas and multiple matched metastases from eight patients to elucidate their phylogenetic relationships. In six of eight patients, we found that genetically distinct cell populations in the primary tumor metastasized in parallel to different anatomic sites, rather than sequentially from one site to the next. In five of these six patients, the metastasizing cells had themselves arisen from a common parental subpopulation in the primary, indicating that the ability to establish metastases is a late-evolving trait. Interestingly, we discovered that individual metastases were sometimes founded by multiple cell populations of the primary that were genetically distinct. Such establishment of metastases by multiple tumor subpopulations could help explain why identical resistance variants are identified in different sites after initial response to systemic therapy. One primary tumor harbored two subclones with different oncogenic mutations in CTNNB1, which were both propagated to the same metastasis, raising the possibility that activation of wingless-type mouse mammary tumor virus integration site (WNT) signaling may be involved, as has been suggested by experimental models. PMID- 26286988 TI - Mapping vaccinia virus DNA replication origins at nucleotide level by deep sequencing. AB - Poxviruses reproduce in the host cytoplasm and encode most or all of the enzymes and factors needed for expression and synthesis of their double-stranded DNA genomes. Nevertheless, the mode of poxvirus DNA replication and the nature and location of the replication origins remain unknown. A current but unsubstantiated model posits only leading strand synthesis starting at a nick near one covalently closed end of the genome and continuing around the other end to generate a concatemer that is subsequently resolved into unit genomes. The existence of specific origins has been questioned because any plasmid can replicate in cells infected by vaccinia virus (VACV), the prototype poxvirus. We applied directional deep sequencing of short single-stranded DNA fragments enriched for RNA-primed nascent strands isolated from the cytoplasm of VACV-infected cells to pinpoint replication origins. The origins were identified as the switching points of the fragment directions, which correspond to the transition from continuous to discontinuous DNA synthesis. Origins containing a prominent initiation point mapped to a sequence within the hairpin loop at one end of the VACV genome and to the same sequence within the concatemeric junction of replication intermediates. These findings support a model for poxvirus genome replication that involves leading and lagging strand synthesis and is consistent with the requirements for primase and ligase activities as well as earlier electron microscopic and biochemical studies implicating a replication origin at the end of the VACV genome. PMID- 26286989 TI - NH4(+) triggers the release of astrocytic lactate via mitochondrial pyruvate shunting. AB - Neural activity is accompanied by a transient mismatch between local glucose and oxygen metabolism, a phenomenon of physiological and pathophysiological importance termed aerobic glycolysis. Previous studies have proposed glutamate and K(+) as the neuronal signals that trigger aerobic glycolysis in astrocytes. Here we used a panel of genetically encoded FRET sensors in vitro and in vivo to investigate the participation of NH4(+), a by-product of catabolism that is also released by active neurons. Astrocytes in mixed cortical cultures responded to physiological levels of NH4(+) with an acute rise in cytosolic lactate followed by lactate release into the extracellular space, as detected by a lactate sniffer. An acute increase in astrocytic lactate was also observed in acute hippocampal slices exposed to NH4(+) and in the somatosensory cortex of anesthetized mice in response to i.v. NH4(+). Unexpectedly, NH4(+) had no effect on astrocytic glucose consumption. Parallel measurements showed simultaneous cytosolic pyruvate accumulation and NADH depletion, suggesting the involvement of mitochondria. An inhibitor-stop technique confirmed a strong inhibition of mitochondrial pyruvate uptake that can be explained by mitochondrial matrix acidification. These results show that physiological NH4(+) diverts the flux of pyruvate from mitochondria to lactate production and release. Considering that NH4(+) is produced stoichiometrically with glutamate during excitatory neurotransmission, we propose that NH4(+) behaves as an intercellular signal and that pyruvate shunting contributes to aerobic lactate production by astrocytes. PMID- 26286990 TI - Cyclin-dependent kinase 5 activates guanine nucleotide exchange factor GIV/Girdin to orchestrate migration-proliferation dichotomy. AB - Signals propagated by receptor tyrosine kinases (RTKs) can drive cell migration and proliferation, two cellular processes that do not occur simultaneously--a phenomenon called "migration-proliferation dichotomy." We previously showed that epidermal growth factor (EGF) signaling is skewed to favor migration over proliferation via noncanonical transactivation of Galphai proteins by the guanine exchange factor (GEF) GIV. However, what turns on GIV-GEF downstream of growth factor RTKs remained unknown. Here we reveal the molecular mechanism by which phosphorylation of GIV by cyclin-dependent kinase 5 (CDK5) triggers GIV's ability to bind and activate Galphai in response to growth factors and modulate downstream signals to establish a dichotomy between migration and proliferation. We show that CDK5 binds and phosphorylates GIV at Ser1674 near its GEF motif. When Ser1674 is phosphorylated, GIV activates Galphai and enhances promigratory Akt signals. Phosphorylated GIV also binds Galphas and enhances endosomal maturation, which shortens the transit time of EGFR through early endosomes, thereby limiting mitogenic MAPK signals. Consequently, this phosphoevent triggers cells to preferentially migrate during wound healing and transmigration of cancer cells. When Ser1674 cannot be phosphorylated, GIV cannot bind either Galphai or Galphas, Akt signaling is suppressed, mitogenic signals are enhanced due to delayed transit time of EGFR through early endosomes, and cells preferentially proliferate. These results illuminate how GIV-GEF is turned on upon receptor activation, adds GIV to the repertoire of CDK5 substrates, and defines a mechanism by which this unusual CDK orchestrates migration-proliferation dichotomy during cancer invasion, wound healing, and development. PMID- 26286992 TI - Topological Bloch bands in graphene superlattices. AB - We outline a designer approach to endow widely available plain materials with topological properties by stacking them atop other nontopological materials. The approach is illustrated with a model system comprising graphene stacked atop hexagonal boron nitride. In this case, the Berry curvature of the electron Bloch bands is highly sensitive to the stacking configuration. As a result, electron topology can be controlled by crystal axes alignment, granting a practical route to designer topological materials. Berry curvature manifests itself in transport via the valley Hall effect and long-range chargeless valley currents. The nonlocal electrical response mediated by such currents provides diagnostics for band topology. PMID- 26286991 TI - IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs. AB - The series of events leading to tertiary lymphoid organ (TLO) formation in mucosal organs following tissue damage remain unclear. Using a virus-induced model of autoantibody formation in the salivary glands of adult mice, we demonstrate that IL-22 provides a mechanistic link between mucosal infection, B cell recruitment, and humoral autoimmunity. IL-22 receptor engagement is necessary and sufficient to promote differential expression of chemokine (C-X-C motif) ligand 12 and chemokine (C-X-C motif) ligand 13 in epithelial and fibroblastic stromal cells that, in turn, is pivotal for B-cell recruitment and organization of the TLOs. Accordingly, genetic and therapeutic blockade of IL-22 impairs and reverses TLO formation and autoantibody production. Our work highlights a critical role for IL-22 in TLO-induced pathology and provides a rationale for the use of IL-22-blocking agents in B-cell-mediated autoimmune conditions. PMID- 26286993 TI - Disruption of hippocampal-prefrontal cortex activity by dopamine D2R-dependent LTD of NMDAR transmission. AB - Functional connectivity between the hippocampus and prefrontal cortex (PFC) is essential for associative recognition memory and working memory. Disruption of hippocampal-PFC synchrony occurs in schizophrenia, which is characterized by hypofunction of NMDA receptor (NMDAR)-mediated transmission. We demonstrate that activity of dopamine D2-like receptors (D2Rs) leads selectively to long-term depression (LTD) of hippocampal-PFC NMDAR-mediated synaptic transmission. We show that dopamine-dependent LTD of NMDAR-mediated transmission profoundly disrupts normal synaptic transmission between hippocampus and PFC. These results show how dopaminergic activation induces long-term hypofunction of NMDARs, which can contribute to disordered functional connectivity, a characteristic that is a hallmark of psychiatric disorders such as schizophrenia. PMID- 26286995 TI - Tocopherol and annatto tocotrienols distribution in laying-hen body. AB - The impact of supplementing laying-hen feed with annatto tocotrienols (T3s) and alpha-tocopherol on the distribution of various forms of vitamin E and cholesterol throughout the hen's body was evaluated. A total of 18 organs or tissues (skin, fat pad, liver and gall bladder, heart, oviduct, forming yolk, laid yolk, lungs, spleen, kidney, pancreas, gizzard, digestive tract, brain, thigh, breast, manure, and blood) were collected after 7 wk of feeding on diets enriched with various levels of alpha-tocopherol and annatto extract that contained gamma-T3 and delta-T3. Tissue weights, contents of lipid, alpha tocopherol, gamma-T3, delta-T3, cholesterol, and fatty acid composition of extracted lipids from the collected organs and tissues were determined. Tissue weight and lipid content did not change significantly with feed supplementation treatments, except that the liver became heavier with increased levels of supplementation. Overall, the main organs that accumulated the supplemented vitamin E were fat pad, liver and gall bladder, oviduct, forming yolks, laid yolks, kidney, brain, thigh, and breast. Much of annatto gamma-T3 and delta-T3 (> 90%) was found in the manure, indicating poor uptake. In some tissues (brain and oviduct,) a significant increase in polyunsaturated fatty acids was seen with increased supplementation. Alpha-tocopherol impacted the transfer of gamma-T3 to forming and laid yolks, but did not impact delta-T3 transfer. No significant differences were found in most of the tissues in cholesterol, except a reduction in heart, based on tissue as-is. Blood samples showed large variations in individual hens with no significant differences in total and HDL cholesterol, or total triacylglycerols. Supplementing feed with annatto T3s and alpha-tocopherol showed that the vitamin E profile and distribution of the laying-hen body can be altered, but to different extents depending on tissue. The result of this research has significance in enhancing meat nutrient content. PMID- 26286994 TI - Age-related profiling of DNA methylation in CD8+ T cells reveals changes in immune response and transcriptional regulator genes. AB - Human ageing affects the immune system resulting in an overall decline in immunocompetence. Although all immune cells are affected during aging, the functional capacity of T cells is most influenced and is linked to decreased responsiveness to infections and impaired differentiation. We studied age-related changes in DNA methylation and gene expression in CD4+ and CD8+ T cells from younger and older individuals. We observed marked difference between T cell subsets, with increased number of methylation changes and higher methylome variation in CD8+ T cells with age. The majority of age-related hypermethylated sites were located at CpG islands of silent genes and enriched for repressive histone marks. Specifically, in CD8+ T cell subset we identified strong inverse correlation between methylation and expression levels in genes associated with T cell mediated immune response (LGALS1, IFNG, CCL5, GZMH, CCR7, CD27 and CD248) and differentiation (SATB1, TCF7, BCL11B and RUNX3). Our results thus suggest the link between age-related epigenetic changes and impaired T cell function. PMID- 26286996 TI - Isolation and culture of chicken primordial follicles. AB - The establishment of a primordial follicle culture system is important for the study of follicular development. Hence, the objective of this study was to isolate chicken primordial follicles and establish culture methods. Ovaries from 2-wk-old chickens were treated with trypsin-EDTA, collagenase II, or collagenase type IA, along with a mechanical isolation technique. Isolated follicles were cultured under different conditions. Results showed a significant difference in the follicular recovery and survival rates among different enzymes and methods used. The maximal follicular yield was obtained by trypsin+EDTA and collagenase II digestion, followed by collagenase type IA digestion. However, the highest follicular viability rate was observed in groups of collagenase type IA digestion and the mechanical isolation method. Enzymatic treatment resulted in higher misshapen oocytes or follicles, though the diameters of the follicles were not significantly changed. In addition, our follicle culture results for different conditions showed maximal survival rates of primordial follicles in alginate hydrogel beads after 12 d of culture. Thus, we successfully established methods for isolating and culturing chicken primordial follicles. The present method will greatly facilitate investigation of the regulation of follicular development. PMID- 26286997 TI - Identification and characterization of transcript variants of chicken peroxisome proliferator-activated receptor gamma. AB - Peroxisome proliferator-activated receptor gamma regulates adipogenesis. The genomic structure of the chicken peroxisome proliferator-activated receptor gamma (cPPARgamma) gene has not been fully characterized, and only one cPPARgamma gene mRNA sequence has been reported in genetic databases. Using 5' rapid amplification of cDNA ends, we identified five different cPPARgamma mRNAs that are transcribed from three transcription initiation sites. The open reading frame analysis showed that these five cPPARgamma transcript variants (cPPARgamma1 to 5) could encode two cPPARgamma protein isoforms (cPPARgamma1 and cPPARgamma2), which differ only in their N-terminal region. Quantitative real-time RT-PCR analysis showed that, of these five cPPARgamma transcript variants, cPPARgamma1 was ubiquitously highly expressed in various chicken tissues, including adipose tissue, liver, kidney, spleen and duodenal; cPPARgamma2 was exclusively highly expressed in adipose tissue; cPPARgamma3 was highly expressed in adipose tissue, kidney, spleen and liver; cPPARgamma4 and cPPARgamma5 were ubiquitously weakly expressed in all the tested tissues, and comparatively, cPPARgamma5 was highly expressed in adipose tissue, heart, liver and kidney. The comparison of the expression of the five cPPARgamma transcript variants showed that adipose tissue cPPARgamma1 expression was significantly higher in the fat line than in the lean line from 2 to 7 wk of age (P < 0.05 or P < 0.01). Adipose tissue cPPARgamma3 expression was significantly higher in the fat line than in the lean line at 3, 5 and 6 wk of age (P < 0.01, P < 0.05), but lower at 4 wk of age (P < 0.05). Adipose tissue cPPARgamma5 expression was significantly higher in the fat line than in the lean line at 3, 4, and 6 wk of age (P < 0.01) and at 2 and 7 wk of age (P < 0.05). This is the first report of transcript variants and protein isoforms of cPPARgamma gene. Our findings provided a foundation for future investigations of the function and regulation of cPPARgamma gene in adipose tissue development. PMID- 26286998 TI - Evaluation of yeast dietary supplementation in broilers challenged or not with Salmonella on growth performance, cecal microbiota composition and Salmonella in ceca, cloacae and carcass skin. AB - The dietary supplementation of Saccharomyces cerevisiae var. boulardii was evaluated in broilers challenged or not challenged with Salmonella Enteritidis (SE) using a 2 * 2 factorial arrangement. Depending on yeast inclusion at 0 (C) or 1 * 109 cfu/kg diet (Y) and SE challenge (0 or log 6.3 cfu/bird) on d 15, the experiment had four treatments C, Y, C-SE, and Y-SE, respectively. Each treatment had seven replicate floor pens with 15 broilers. Growth performance responses were determined weekly and overall for the 5 week experimental period. Salmonella levels and prevalence in ceca, cloacae, and carcass skin were determined by culture procedures, while cecal microbiota was determined by real time PCR. Yeast supplementation had no effect (PY > 0.05) on growth performance. For the overall post SE-challenge period (i.e., wk 3 to wk 5), Salmonella reduced body weight gain (BWG) (PSE < 0.001), feed intake (FI) (PSE = 0.032), and the European production efficiency (EPEF) factor (PSE = 0.005). Broilers Y-SE had higher (P < 0.001) overall BW gain compared to C-SE ones. Overall mortality was 2.14% and did not differ (P > 0.05) between treatments. Reduced Salmonella levels in the cloacae (P = 0.014) and on the breast skin (P = 0.006) and lower prevalence on the neck skin (P = 0.007) were noted for treatment Y-SE compared to C-SE. Yeast supplementation did not have an effect (P > 0.05) on cecal microbiota composition at d 1 and d 21 post SE-challenge. On the contrary, SE-challenge reduced cecal levels of total bacteria (PSE = 0.002), E. coli (PSE = 0.006), Bifidobacterium spp. (PSE = 0.006), Bacteroides spp. (PSE = 0.010), and Clostridial populations belonging to cluster I and cluster XIVa, (PSE = 0.047 and PSE = 0.001, respectively) on d 1 post SE-challenge. At 21 d post SE-challenge, only the levels of cecal Lactobacillus spp. (PSE = 0.001) and Bifidobacterium spp. (PSE = 0.049) were reduced compared to the non SE-challenged groups. In conclusion, yeast supplementation in SE challenged broilers (Y-SE) was beneficial for growth performance and reduced Salmonella presence compared to C-SE ones. The disturbance of cecal microbiota balance by SE merits further investigation for potential implications in gut and overall bird health. PMID- 26286999 TI - High pressure spray with water shows similar efficiency to trimming in controlling microorganisms on poultry carcasses. AB - A study was conducted to evaluate a high pressure spray (HPS) with water as an alternative to trimming to remove gastrointestinal contamination on poultry carcasses and improve microbiological quality. The study was conducted under commercial conditions in 5 slaughter plants with one plant presenting approximately 5% of carcasses with visible gastrointestinal contamination (VGC), and the others showing approximately 12% of VGC. In all 5 plants, carcasses were sampled from the slaughter line and separated into 6 groups corresponding to 3 different treatments: A) carcasses with VGC before and after trimming; B) carcasses with VGC before and after HPS; and C) carcasses with no VGC before and after HPS. At the end of Trial A and prior to Trials B and C, an HPS equipment was installed before the end of the slaughter line. The HPS equipment was operated with 10 kgf/cm2 of pressure and 1.5 L of potable water per carcass. Carcasses were analyzed using a rinsing procedure, and the following microbiological parameters were evaluated: the prevalence of Salmonella and Campylobacter, the abundance of Escherichia coli (EC), Enterobacteriaceae (EB), and the Total Viable Count (TVC). Salmonella was found in all plants at a prevalence ranging from 0.8% (plant 1) to 17.3% (plant 5), and the difference between plants was significant (P < 0.05%). The prevalence of Campylobacter ranged from 2.1 (plant 1) to 18.6% (plant 4) (P < 0.05%). The prevalence of Campylobacter was similar in plants 2, 3, and 5, and a significant difference (P < 0.05%) was observed compared to plants 1 and 4. In all plants, the EC, EB, and TVC counts did not show a significant difference (P > 0.05%) in any treatments. These results demonstrate that HPS with water is an alternative method for removing VGC and improving or maintaining the microbiological quality and safety of broiler carcasses. PMID- 26287000 TI - Dietary acylated starch improves performance and gut health in necrotic enteritis challenged broilers. AB - Resistant starch has been reported to act as a protective agent against pathogenic organisms in the gut and to encourage the proliferation of beneficial organisms. This study examined the efficacy of acetylated high amylose maize starch (SA) and butyralated high-amylose maize starch (SB) in reducing the severity of necrotic enteritis (NE) in broilers under experimental challenge. A total of 720 one-day-old male Ross 308 chicks were assigned to 48 floor pens with a 2 * 4 factorial arrangement of treatments. Factors were a) challenge: no or yes; and b) feed additive: control, antibiotics (AB), SA, or SB. Birds were challenged with Eimeria and C. perfringens according to a previously reported protocol. On d 24 and 35, challenged birds had lower (P < 0.001) livability (LV), weight gain (WG), and feed intake (FI) compared to unchallenged birds. Challenged birds fed SA and SB had higher FI and WG at d 24 and 35 (P < 0.05) compared to birds fed the control diet, while being significantly lower than those fed AB. Unchallenged birds fed SA or SB had higher FI at d 24 and 35 compared to those fed the control diet (P < 0.05). Birds fed SB had increased (P < 0.001) jejunal villus height/crypt depth (VH:CD) ratios at d 15, increased ileal (P < 0.001) and caecal (P < 0.001) butyrate levels at d 15 and 24, and decreased (P < 0.01) caecal pH at d 15. Birds fed SA had increased (P < 0.001) ileal acetate content at d 24 and decreased (P < 0.01) caecal pH at d 15. These results demonstrated that dietary acylated starch improved WG in birds challenged with necrotic enteritis. Depending on the acid used, starch acylation also offers a degree of specificity in short chain fatty acid (SCFA) delivery to the lower intestinal tract which improves gut health. PMID- 26287001 TI - Methods for assessment of keel bone damage in poultry. AB - Keel bone damage (KBD) is a critical issue facing the laying hen industry today as a result of the likely pain leading to compromised welfare and the potential for reduced productivity. Recent reports suggest that damage, while highly variable and likely dependent on a host of factors, extends to all systems (including battery cages, furnished cages, and non-cage systems), genetic lines, and management styles. Despite the extent of the problem, the research community remains uncertain as to the causes and influencing factors of KBD. Although progress has been made investigating these factors, the overall effort is hindered by several issues related to the assessment of KBD, including quality and variation in the methods used between research groups. These issues prevent effective comparison of studies, as well as difficulties in identifying the presence of damage leading to poor accuracy and reliability. The current manuscript seeks to resolve these issues by offering precise definitions for types of KBD, reviewing methods for assessment, and providing recommendations that can improve the accuracy and reliability of those assessments. PMID- 26287002 TI - Pathogenicity of newly emergent turkey arthritis reoviruses in chickens. AB - Turkey arthritis reoviruses (TARVs) were isolated recently from gastrocnemius and digital flexor tendons of lame turkeys with swollen joints and tenosynovitis. These TARVs were genetically different from chicken arthritis reoviruses (CARVs) and produced gastrocnemius tenosynovitis when inoculated into turkey poults. The purpose of this study was to determine the pathogenicity of TARVs in chickens. One-week-old, specific-pathogen-free chicks were inoculated with either a TARV (TARV-MN2 or TARV-O'Neil) or CARV via oral, intratracheal, or footpad routes. At 2 and 3 weeks post inoculation (PI), a subset of chicks from each group was euthanized followed by collection of tissues for real-time RT-PCR (rRT-PCR), virus isolation, and histopathology. Chickens inoculated with CARV via intratracheal and footpad routes developed gastrocnemius lymphocytic tenosynovitis at 2 and 3 weeks PI. Both TARV-MN2 and TARV-O'Neil induced gastrocnemius lymphocytic tenosynovitis in chicks inoculated only via the footpad route at 2 and 3 weeks PI. Although there was no evidence of clinical lameness, the virus was present in leg tendons, internal organs, and intestines of all TARV inoculated chicks regardless of route of inoculation, as indicated by rRT-PCR and virus isolation. These results indicate that TARVs do not produce gastrocnemius tenosynovitis in chicks by 3 weeks PI when administered via the most probable natural route (e.g., oral and intratracheal). Further studies are needed to determine the long term effects these viruses might play in inducing lameness in chickens. PMID- 26287003 TI - Application of low-gossypol cottonseed meal in laying hens' diet. AB - An experiment was conducted to evaluate the application of dietary low-gossypol cottonseed meal (LCSM) in layers' diets. A total of 432 40-week-old Hy-line W36 laying hens were allocated to one of the six dietary treatments with 6 replicates of 12 birds each. The control group was fed a corn-soybean meal basal diet, and the 4 experimental diets consisted of a basal diet with 50, 98.3, 144.2, or 189 g/kg LCSM, respectively (correspondingly 25%, 50%, 75%, 100% dietary protein provided by soybean meal were replaced by LCSM). The sixth group was fed a basal diet supplemented with free gossypol (FG group). The feeding trial lasted for 12 weeks. The results showed that no significant difference was observed on egg production or feed conversion ratio (FCR, feed/egg, g/g) among all groups, but feed intake and egg weight were significantly decreased in the 189 g/kg LCSM group in weeks 46 to 51 (P < 0.05). A significant decrease was not observed in shell strength, shell thickness, and yolk color in all periods, but Haugh unit, albumen height, and egg white protein content were reduced in 189 g/kg LCSM group in weeks 46 to 51 (P < 0.05). No significant differences were found between the control and FG group. There was no obvious difference on plasma levels of total protein, blood urea nitrogen, uric acid, and activities of albumen, alanine aminotransferase, aspartate aminotransferase and the histopathology of liver, kidney, and oviduct in all groups. In conclusion, decreasing feed intake, egg weight, and egg quality were observed in the 189 g/kg LCSM group. However, the adverse effect was not relevant to the presence of FG in LCSM. Dietary LCSM supplementation of 98.3 g/kg was recommended with optimum FCR and without adverse effect on egg production, quality, and health of layers. PMID- 26287011 TI - Lipids: The Macronutrient That Deserves Some Respect and Airtime. PMID- 26287012 TI - Measuring Protein Breakdown in Clinical Scenarios With Limited Accessible Tools. PMID- 26287013 TI - Assessing Nitrogen Balance in Older Patients. PMID- 26287014 TI - Response to "Peripherally Inserted Central Catheter for Use in Home Parenteral Nutrition: A 4-Year Follow-Up Study". PMID- 26287015 TI - Regarding the Response to "Peripherally Inserted Central Catheter for Use in Home Parenteral Nutrition: A 4-Year Follow-up Study". PMID- 26287016 TI - Body Composition Tools for Assessment of Adult Malnutrition at the Bedside: A Tutorial on Research Considerations and Clinical Applications. AB - Because of the key role played by the body's lean tissue reserves (of which skeletal muscle is a major component) in the response to injury and illness, its maintenance is of central importance to nutrition status. With the recent development of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition diagnostic framework for malnutrition, the loss of muscle mass has been recognized as one of the defining criteria. Objective methods to evaluate muscle loss in individuals with acute and chronic illness are needed. Bioimpedance and ultrasound techniques are currently the best options for the clinical setting; however, additional research is needed to investigate how best to optimize measurements and minimize error and to establish if these techniques (and which specific approaches) can uniquely contribute to the assessment of malnutrition, beyond more subjective evaluation methods. In this tutorial, key concepts and statistical methods used in the validation of bedside methods to assess lean tissue compartments are discussed. Body composition assessment methods that are most widely available for practice and research in the clinical setting are presented, and clinical cases are used to illustrate how the clinician might use bioimpedance and/or ultrasound as a tool to assess nutrition status at the bedside. Future research needs regarding malnutrition assessment are identified. PMID- 26287017 TI - JPEN Journal Club 15. Putting Trials in Perspective. PMID- 26287018 TI - Editorial. PMID- 26287019 TI - Perioperative Considerations for Children With Right Ventricular Dysfunction and Failing Fontan. AB - The survival of patients with congenital heart diseases (CHD) has increased in the past decades, resulting in the identification of new characteristics of chronic comorbidities observed in pediatric and adults with CHD. Patients with CHD can present with a broad clinical spectrum of manifestations of congestive heart failure (CHF) at any point throughout their lives that may be related to anatomical or surgical variables. This article focuses on the perioperative assessment of patients with CHD and CHF, with an emphasis on pathophysiologic, diagnostic, and therapeutic alternatives in patients with right ventricular failure and failing Fontan circulation. We also provide descriptions of the effects of sedatives and anesthetics commonly used in this population in diagnostic or invasive procedures. PMID- 26287020 TI - Prevalence of children whose parents have a substance use disorder: Findings from a Swedish general population survey. AB - AIMS: The present study examined the prevalence of Swedish children living with at least one parent whom has a substance use disorder (SUD), i.e. either an alcohol use disorder (AUD) or a drug use disorder (DUD). METHODS: A 2013 cross sectional survey of a nationally representative sample (n = 15,576) of the Swedish adult population 17-84 years of age was used. The response rate was 59.3%. SUDs were measured using selected parts of the Mini International Neuropsychiatric Interview (MINI), derived from the 4th edition of the diagnostic and statistical manual of mental disorders (DSM-IV). In total, 3778 parents with 7448 children under the age of 18 years participated. RESULTS: The proportion of children whose parent had a SUD was 4.6%, implying that around 90,000 children in Sweden experience this situation. Having a parent with an AUD was most common (3.7%), while 0.7% and 0.2% had a parent with a DUD and both (AUD plus DUD), respectively. CONCLUSIONS: Our results showed that a substantial number of children in Sweden have parents with a SUD and that it is important to consider both alcohol and drugs, when estimating the size of this group. Our findings call for further strategies to support these children and their families. PMID- 26287021 TI - Angiotensin-(1-7): beyond its central effects on blood pressure. AB - Angiotensin (Ang) (1-7) is the main component of the depressor and protective arm of the renin-angiotensin system. Ang-(1-7) induces vasodilation, natriuresis and diuresis, cardioprotection, inhibits angiogenesis and cell growth and opposes the pressor, proliferative, profibrotic, and prothrombotic actions mediated by Ang II. Centrally, Ang-(1-7) induces changes in mean arterial pressure and this effect may be linked with its inhibitory neuromodulatory action on norepinephrine neurotransmission. The present review is focused on the role of Ang-(1-7) as a protective agent in the brain. PMID- 26287023 TI - Teeth, genes, and genealogy. PMID- 26287022 TI - Ten-year experience in subclavian revascularisation. A parallel comparative observational study. AB - INTRODUCTION: Subclavian stenosis has a prevalence of approximately 2% in the community, and 7% within a clinical population. It is closely linked with hypertension and smoking. There is a relative paucity of published data to inform clinicians on the optimal mode of treatment for subclavian artery stenosis. OBJECTIVES: To compare clinical outcomes of subclavian bypass surgery with that of subclavian endovascular re-vascularisation. Endpoints were survival time, re intervention-free survival, and symptom-free survival. METHOD: In all, 21 subclavian interventions were performed from 2000 to 2010. We compared angioplasty vs angioplasty with stenting vs bypass. RESULTS: Technical success was 100% in all groups. Symptom-free survival, at 70 months, was 60% in the angioplasty group, 100% in the angioplasty and stenting group and 75% in the bypass group. Re-intervention rate was 40% in the angioplasty group, 0% in the angioplasty and stenting group and 25% in the bypass group. Median time for re intervention was 9.5 months in angioplasty patients and 36 months in bypass patients (p = 0.102). Target lesion revascularisation was 20.0% for angioplasty procedures, 16.67% for angioplasty and stenting and 25% for bypass procedures. CONCLUSION: Angioplasty with stenting provides improved symptom-free survival and freedom from re-intervention in patients with symptomatic subclavian artery stenosis. PMID- 26287024 TI - All-ceramic inlay-retained fixed dental prostheses: An update. AB - Inlay-retained fixed dental prostheses (IRFDPs) represent a minimally invasive alternative to conventional fixed dental prostheses (FDPs) to replace single posterior missing teeth. The aim of the present review article is to assess the clinical outcome of different IRFDPs in order to derive recommendations regarding their clinical application. Hence, it is essential to highlight important factors that influence the longevity and success of IRFDPs, such as treatment plan, appropriate case selection with proper indications, as well as tooth preparation. Furthermore, a good understanding of bonding technologies and awareness of pretreatment procedures for different materials are indispensable for the long term success of IRFDPs. PMID- 26287025 TI - The pain-related behavior and pain perception associated with computerized anesthesia in pulpotomies of mandibular primary molars: A randomized controlled trial. AB - OBJECTIVE: The purpose of the study was to compare the pain-related behavior and the pain perception associated with three anesthetic techniques in pulpotomies of primary mandibular second molars: traditional inferior alveolar nerve block (IANB), IANB with computer-controlled local anesthetic delivery (CCLAD), and intraligamental anesthesia with CCLAD. METHOD AND MATERIALS: The sample comprised 91 randomly selected healthy children aged 5 to 9 years, who were scheduled for pulpotomy in the mandibular second molar. Patients were divided into three groups according to the type of anesthesia received. Group A received traditional IANB, group B received IANB with CCLAD, and group C received intraligamental anesthesia with CCLAD. Pain-related behavior and pain perception levels were assessed using the established behavior code and the Wong-Baker FACES Pain Rating Scale respectively. RESULTS: The mean of pain-related behavior was significantly lower (P < .001) in the intraligamental anesthesia with CCLAD group than in the other two groups. The pain perception scores were significantly higher in the traditional IANB group than in the IANB with CCLAD group, and the intraligamental anesthesia with CCLAD group (P = .044 and P < .001 respectively). The mean +/- SD of the pain perception of IANB was 1.39 +/- 0.200, IANB with CCLAD was 0.87 +/- 0.133 and ILA with CCLAD was 0.13 +/- 0.063. CONCLUSION: Intraligamental anaesthesia with CCLAD was clearly associated with less pain than the IANB with or without CCLAD. PMID- 26287026 TI - Glutathione-stabilized palladium nanozyme for colorimetric assay of silver(I) ions. AB - Glutathione-capped Pd nanoparticles with a size of 1.4-3.5 nm are facilely synthesized for peroxidase nanomimetics. The molar ratio of [Na2PdCl4]/[GSH] greatly affects the physicochemical properties including particle sizes, surface charge states and enzymatic activities. The most efficient Pd-based nanozyme, consisting of approximately 57% metallic Pd(0) species with an average diameter of 2.6 nm, exhibits the K(m) value of 0.068 mM toward 3,3',5,5' tetramethylbenzidine and 156 mM toward hydrogen peroxide. Ag(+) selectively binds to Pd(0) species through metallophilic interactions and induces an apparent aggregation of Pd nanoparticles. This is the first report that Ag(+) significantly inhibits the peroxidase mimicking activity of Pd nanoparticles. A Pd-based nanozyme is employed to explore colorimetric detection of Ag(+) with the limit of detection of 1.2 nM. This developed sensing system is potentially applicable for quantitative detection of Ag(+) in drinking water as well as Ag nanoparticles in aqueous solution. PMID- 26287027 TI - Metal-free carbonyl C(sp(2))-H oxidative alkynylation of aldehydes using hypervalent iodine reagents leading to ynones. AB - A new metal-free tert-butyl hydroperoxide (TBHP)-mediated carbonyl C(sp(2))-H oxidative alkynylation of aldehydes with ethynyl benziodoxolones (EBX) for the synthesis of ynones is described. This method is based on a carbonyl C(sp(2))-H oxidative radical coupling process according to mechanistic studies, and provides a general route to the assembly of diverse ynones with a broad substrate scope and excellent functional-group compatibility. PMID- 26287028 TI - Palladium-catalyzed bisarylation of 3-alkylbenzofurans to 3-arylalkyl-2 arylbenzofurans on water: tandem C(sp(3))-H and C(sp(2))-H activation reactions of 3-alkylbenzofurans. AB - A protocol involving facile sequential C(sp(3))-H and C(sp(2))-H activation reactions of 3-alkylbenzofurans catalyzed by Pd(OAc)2 in the presence of pivalic acid, silver salt, and tricyclohexylphosphine 'on water' was developed. Aryl iodides were used as substrates in a tandem bisarylation reaction to generate 3 arylalkyl-2-arylbenzofurans in moderate to high yields at room temperature. The reaction revealed in this study is a rare example of consecutive C(sp(3))-H and C(sp(2))-H bond activation under mild reaction conditions. PMID- 26287029 TI - Recent trends in the development of vitamin B12 derivatives for medicinal applications. AB - This Feature Article highlights recent developments in the field of vitamin B12 derivatives for medicinal applications. The following topics are emphasized: (1) the development of aquacorrinoids for cyanide detection and detoxification, (2) the use of vitamin B12 conjugates and (3) antivitamins B12 for therapy and diagnosis, and (4) the design of corrinoids as activators of soluble guanylyl cyclase (sGC). PMID- 26287030 TI - Nuclear receptor peroxisome proliferator activated receptor (PPAR) beta/delta in skin wound healing and cancer. AB - We review the functions of peroxisome proliferator activated receptor (PPAR) beta/delta in skin wound healing and cancer. In particular, we highlight the roles of PPARbeta/delta in inhibiting keratinocyte apoptosis at wound edges via activation of the PI3K/PKBalpha/Akt1 pathway and its role during re epithelialization in regulating keratinocyte adhesion and migration. In fibroblasts, PPARbeta/delta controls IL-1 signalling and thereby contributes to the homeostatic control of keratinocyte proliferation. We discuss its therapeutic potential for treating diabetic wounds and inflammatory skin diseases such as psoriasis and acne vulgaris. PPARbeta/delta is classified as a tumour growth modifier; it is activated by chronic low-grade inflammation, which promotes the production of lipids that, in turn, enhance PPARbeta/delta transcription activity. Our earlier work unveiled a cascade of events triggered by PPARbeta/delta that involve the oncogene Src, which promotes ultraviolet-induced skin cancer in mice via enhanced EGFR/Erk1/2 signalling and the expression of epithelial-to-mesenchymal transition (EMT) markers. Interestingly, PPARbeta/delta expression is correlated with the expression of SRC and EMT markers in human skin squamous cell carcinoma. Furthermore, there is a positive interaction between PPARbeta/delta, SRC, and TGFbeta1 at the transcriptional level in various human epithelial cancers. Taken together, these observations suggest the need for evaluating PPARbeta/delta modulators that attenuate or increase its activity, depending on the therapeutic target. PMID- 26287031 TI - Pluripotent stem cells as a cellular model for skin: relevance for physiopathology, cell/gene therapy and drug screening. AB - The skin represents the largest tissue in the human body. Its external part, the epidermis, accomplishes vital functions such as barrier protection, thermoregulation and immune function. The mammalian skin epidermis has been for decades the paradigm for studying the molecular events that occur in tissue homeostasis and repair. Many genes and signaling pathways have been identified by the use of manipulated transgenic and KO mice. However, despite numerous elegant transgenic mice experiments, absence of an appropriate in vitro model system has hampered the molecular study of the early events responsible for epidermal and dermal commitments, stages at which congenital genetic alterations are responsible for hundreds of rare skin diseases. For most of them, etiology and treatment are still missing. Here we review the last decade of studies aimed at designing cellular models from pluripotent stem cells (PSC) that recapitulate in vitro the main molecular steps of skin formation. As described below, PSC-based models are powerful tools to (i) clarify early molecular events that occur during epithelial/mesenchymal interactions, (ii) produce in large amount skin cells that could become an alternative for cell/gene therapies and (iii) screen for therapeutic compounds to treat genodermatoses. PMID- 26287032 TI - Effect of ArginMax on sexual functioning and quality of life among female cancer survivors: results of the WFU CCOP Research Base Protocol 97106. AB - BACKGROUND: Problems with sexual functioning are common following therapy for breast and gynecologic cancers, although there are few effective treatments. OBJECTIVE: To assess the impact of ArginMax, a nutritional supplement comprised of extracts of L-arginine, ginseng, gingko, and damiana, as well as multivitamins and minerals, on sexual functioning and quality of life in female cancer survivors. METHODS: This was a 12-week, randomized, placebo-controlled trial of eligible patients who were 6 months or more from active treatment and reporting problems with sexual interest, satisfaction, and functioning after therapy. The participants took 3 capsules of Arginmax or placebo twice daily. Outcome measures were the Female Sexual Function Inventory (FSFI) and the Functional Assessment of Cancer Therapy - General (FACT-G). Assessments were done at baseline, 4, 8, and 12 weeks. RESULTS: 186 patients with a median age of 50 years were accrued between May 10, 2007 and March 24, 2010. 76% of the patients were non-Hispanic white. Most had breast or a gynecologic cancer (78% and 12%, respectively). At 12 weeks, there were no differences between the ArginMax group (n = 96) and placebo (n = 92) group in sexual desire, arousal, lubrication, orgasm,satisfaction or pain. However, FACT-G total scores were significantly better for participants who took ArginMax compared with those who took placebo (least squares [LS] means, 87.5 vs 82.9, respectively; P = .009). The Fact-G subscales that were most affected were Physical (25.37 vs. 23.51, P = .001) and Functional Well-Being (22.46 vs. 20.72, P = .007). Toxicities were similar for both groups. LIMITATIONS: Study results are limited by a lack of data on the participants' psychological and physical symptoms and sexual partner variables. CONCLUSIONS: ArginMax had no significant impact on sexual functioning, but patient quality of life was significantly better at 12 weeks in participants who received ArginMax. PMID- 26287033 TI - Assessing the impact of a targeted electronic medical record intervention on the use of growth factor in cancer patients. AB - BACKGROUND: Patients receiving chemotherapy are at risk for febrile neutropenia following treatment. The American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) recommend screening patients for risk of febrile neutropenia and risk stratification based on likelihood of febrile neutropenia events. The impact of the implementation of an electronic medical record (EMR) system on physician compliance with growth factor support guidelines has not been studied. OBJECTIVE: To investigate whether implementation of automated orders in EMRs can improve adherence to national guidelines in prophylactic G-CSF use in chemotherapy patients. METHODS: A retrospective chart review of cancer patients receiving chemotherapy from January 1, 2007 to August 1, 2008 (pre- EMR) and January 1, 2011 to December 31, 2011 (post-EMR) was conducted. Institutional adherence to ASCO and NCCN guidelines for G-CSF after the implementation of automatic electronic orders for pegfilgrastim in patients who received a high-risk chemotherapy regimen were examined. The results were compared with a similar study that had been conducted before the implementation of the EMR system. RESULTS: The number of regimens that included guideline-driven growth factor usage and nonusage was 75.6% in the post-intervention arm, compared with 67.5% in the pre-intervention arm. This is a statistically significant difference between the pre-EMR and post-EMR compliance with national guidelines on growth factor usage ( P = .041, based on chi-square test). The post-EMR implementation data of 1,042 individual new chemotherapy regimens showed correct use of G-CSF in 89.13% high-risk chemotherapy regimens and 58.74% intermediate risk regimens, with risk factors and incorrect usage in 26.23% of intermediate risk regimens without risk factors and 19.34% of low-risk regimens. The appropriateness of use in high- and low-risk regimens was the most compliant, because growth factor was built into chemotherapy plans of high-risk regimens and omitted from low-risk regimens. LIMITATIONS: This project was limited by a change in EMR systems at West Virginia University hospitals on January 1, 2009. All pre- EMR data was collected before 2009 and could not be further collected once the project began in 2013. CONCLUSIONS: Appropriateness of growth factor usage can be improved when integrated into an EMR. This can improve compliance and adherence to national recommendations. Further development and understanding of EMR is needed to improve usage to meet national guidelines, with particular attention paid to integration of risk factors into EMR to improve growth factor usage compliance. PMID- 26287034 TI - Comment. PMID- 26287035 TI - Benjamin Lane Crue 1925-2015. PMID- 26287036 TI - RETRACTION NOTICE. PMID- 26287037 TI - Proceedings of the 19th International Taurine Meeting, May 21-24, 2014, Krakow, Poland. PMID- 26287039 TI - Proceedings of the International Symposium on Understanding Moderate Malnutrition in Children for Effective Interventions, May 26-29, 2014, Vienna, Austria. PMID- 26287038 TI - Re: Introducing the HOPE (Hypospadias Objective Penile Evaluation)-Score: A Validation Study of an Objective Scoring System for Evaluating Cosmetic Appearance in Hypospadias Patients. PMID- 26287040 TI - Response: Lifelong Training Is the End in Sight? PMID- 26287041 TI - Simultaneous PRES and TMA secondary to tacrolimus after allogeneic bone marrow transplant. PMID- 26287042 TI - Vitamin D and breastfeeding: an update. PMID- 26287043 TI - Us? Bad Teeth? Not So Fast, Brits Say.... PMID- 26287044 TI - Arginine Bicarbonate/Calcium Carbonate Soft Chews Seal Open Dentinal Tubules. PMID- 26287045 TI - Five Days to...Poor Health. PMID- 26287046 TI - Study Underscores the Costly Repercussions of Eliminating Adult Dental Coverage Under Medicaid. PMID- 26287047 TI - American Academy of Implant Dentistry Honors Leonard Linkow, DDS, DSMc. PMID- 26287048 TI - Anxiety in Social Situations Increases Risk of Bruxism. PMID- 26287049 TI - Kidney Transplantation--Celebrating 60 Years of Success. PMID- 26287050 TI - Ebola: Maintaining Safety with Knowledge. PMID- 26287051 TI - Reflections on 24 Years of Kidney Transplant Nursing. PMID- 26287052 TI - An Overview of Transplant Immunosuppression--History, Principles, and Current Practices in Kidney Transplantation. AB - From the historical first transplant in 1954 to the current transplant era, tremendous strides have been made in transplant immunology and immunosuppression. The most common immunosuppressive regimens use a combination of agents with differing modes of action to maximize efficacy and minimize the toxicities associated with each class of agent. The general categories of immunosuppressives are glucocorticoids, antimetabolites, calcineurin inhibitors, anti-lymphocyte antibody therapies (monoclonal and polyclonal), costimulation blockers, and mTOR inhibitors. This article reviews immunosuppressant medications, their actions, and significant side effects; discusses clinical management issues of immunosuppression; and describes future directions for the development of immunosuppressive medications. PMID- 26287053 TI - Twenty-Eight Kidney Transplant Recipients and Counting! One Center's Kidney Transplant Chain Experience. AB - With over 101,000 people currently on the waiting list for a kidney transplant, innovative solutions are needed to expand the number of available donor organs. This article describes the experience of one transplant center in using living donor paired exchanges and donor swaps to result in a chain of 28 kidney transplant recipients in the past year. PMID- 26287054 TI - The Independent Living Donor Advocate: An Essential Role for Living Kidney Donation. AB - Prior to 2007, living kidney donors who donated a kidney to a person with chronic kidney disease were screened, educated, and cared for by the same healthcare team caring for the recipient of the transplant. The independent living donor advocate or advocate team was created out of the need to ensure that the rights of the person donating a kidney are protected, respected, and maintained. Transplant programs must now have an advocate or advocate team who is separate from the recipient healthcare team to provide objective support for the donor, without regard for the recipient, and avoid any perception of a conflict of interest between the donor and recipient. PMID- 26287055 TI - The Development of Kidney Transplant Nursing. AB - An analysis of published literature, interviews with early transplant nurses, and other primary source materials shows how evolving medical treatments for rejection, nurses' ability to learn on the job, and their commitment to patients influenced the development of kidney transplantation as a specialized area of practice. The work of these nurses work is discussed in the context of unfolding nursing specialization at the middle of the twentieth century. PMID- 26287056 TI - Understanding the Changes to the National Deceased Donor Allocation System. AB - The national deceased donor kidney allocation system has not been changed since 1986. After many years of study and collaboration, a new policy to revise the system goes into effect on December 4, 2014. This new system is intended to increase access to kidney transplantation and improve the overall success rates. Although the majority of candidates will not be significantly affected by the changes, certain populations of patients are projected to have decreased waiting times. Transplant candidates expected to need a kidney the longest are also more likely to receive a kidney predicted to last the longest. Many educational resources have been provided to transplant centers and have also been made available to patients and referring physicians. PMID- 26287057 TI - BK Virus in Recipients of Kidney Transplants. AB - Since its discovery in 1971, the BK virus, a human polyomavirus, has emerged as a significant cause of renal dysfunction and transplant graft loss in kidney transplant recipients. Improved screening methods have been effective in assisting in the early identification of the virus, and thus, prompt intervention to prevent the progression of the disease. Treatment options for the virus are limited; therefore, lowering immunosuppressive medications should be considered the first line of treatment. Current adjunctive therapies are not guaranteed to control the viral activity and may have limited therapeutic value. PMID- 26287058 TI - Willingness to Consider Non-Directed Kidney Donation. AB - The purpose of the study was to determine whether factors, including knowledge about living kidney donation or acquaintance with a donor or recipient, are related to willingness to consider donating a kidney. Participants were randomly assigned to read (n = 78) or not read (n = 71) educational materials regarding living donation. All participants then completed a living donation knowledge quiz, indicated whether they knew a donor or recipient, and indicated their support for living donation. Knowledge was not related to willingness to consider donation. Acquaintance with a living donor predicated greater willingness to act as a non-directed living donor, as did acquaintance with a transplant recipient. Decisions regarding whether to consider acting as a living organ donor may be related to whether a person is acquainted with an organ donor or a recipient. Emphasizing personal connections to transplant may lead to increased acceptance of living donation. PMID- 26287059 TI - Chronicles of a Living Kidney Donor. PMID- 26287060 TI - Steroid Withdrawal or Avoidance after Kidney Transplant. PMID- 26287061 TI - Do You Know How to Respond to Questions Related to Kidney Donation? PMID- 26287062 TI - New Neotropical species of Hygronemobius Hebard, 1913 (Orthoptera: Grylloidea: Nemobiinae), including a brief discussion of male genitalia morphology and preliminary biogeographic considerations of the genus. AB - Three new Neotropical species of Hygronemobius Hebard are described from Atlantic Forest remnants in southeastern Brazil: Hygronemnobius indaia sp. n. and Hygroneinobius iperoigae sp. n. from the state of Sao Paulo and Hygroneinobius guriri sp. n. from the state of Espirito Santo. We provide photographs of types and male genitalia, and discuss the morphology of male genitalia, taxonomy, calling songs and biogeographic distribution of the genus. PMID- 26287063 TI - Two new species of scalpelliform barnacles (Cirripedia: Thoracica) from the Plio Pleistocene of Cotentin, northwest France. AB - Two new species of pedunculate cirripede are described from the Plio-Pleistocene of Cotentin, northwest France. Scalpellum carentanensis sp. nov. is only the third species of this genus to be recorded from Pliocene strata in Europe. It is characterised by a triangular tergum with an apico-basal fold, without an outward extension, the inner surface of which has the raised part marked by wide growth lines, cut by a groove; the scutum has a ridge between the umbo and the tergo lateral angle, lacks an apico-basal ridge, and possesses a line formed by the convergence of the growth zones; the length of the upper lateral exceeds its width by about 1.25 times, the umbo being situated at one-fifth the length of the plate from the apex. Arcoscalpelluin concavitectum sp. nov. is the second species of this genus on record from the Pliocene of Europe. It possesses a carina with a concave tectum bordered on each side by a smooth rounded rib; the tergum has an apico-basal line formed by the convergence of growth zones; and the upper lateral has the basi-scutal angle more widely truncated than the basi-tergal angle. PMID- 26287064 TI - Insight into the validity of Leptobrachium guangxiense (Anura: Megophryidae): evidence from mitochondrial DNA sequences and morphological characters. AB - Lepobrachiun guangxiense Fei, Mo, Ye and Jiang, 2009 (Anura: Megophryidae), is presently thought to be endemic to Shangsi, Guangxi Province, China. A molecular phylogenetic analysis and morphological data were performed to gain insight into the phylogenetic position of this species. Maximum parsimony, maximum likelihood, and Bayesian inference methods were employed to reconstruct phylogenetic relationship, using 1914 bp of sequences from mtDNA genes of 12S rRNA, tRNAVal and 16S rRNA. Topologies revealed that L. guangxiense and Tam Dao (Vietnam) L. chapaense lineage (3A) formed a monophyletic group with well-supported values. The uncorrected p-distance of ~1.4k bp 16S rRNA data-sets between Tam Dao L. chapaense lineage (3A) and L. guangxiense is only 0.1%. Morphologically, L. guangxiense and Tam Dao L. chapaense lineage (3A) shared the same characters, and are distinguishable from "true" L. chapaense from the type locality in Sa Pa, Vietnam. Based on morphological characters and mitochondrial DNA, we suggested that the Tam Dao lineages of L. chapaense are conspecific with L. guangxiense. This represents a range extension for L. guangxiense, and a new country record for Vietnam. PMID- 26287065 TI - Two new bamboo-feeding species of the genus Neocarpia Tsaur & Hsu (Hemiptera: Fulgoromorpha: Cixiidae: Eucarpiini) from Guizhou Province, China. AB - Two new bamboo-feeding species of the cixiid planthopper genus Neocarpia Tsaur & Hsu, 2003 (Hemiptera: Fulgoromorpha: Cixiidae: Eucarpiini), N. bidentata sp. nov. (Guizhou: Xishui) and N. hamata sp. nov. (Guizhou, Yanhe), from southwest China, are described and illustrated. The generic characteristics are redefined. A key and a checklist to the known species of this genus in the world are provided. PMID- 26287066 TI - Description of Alocobisium tibetense sp. nov., representing the first record of the pseudoscorpion family Syarinidae (Arachnida: Pseudoscorpiones) from China. AB - Alocobisiun tibetense sp. nov. is described from Xizang Autonomous Region, representing the first record of Syarinidae from China. Alocobisium rahmi Beier, 1976 is re-described from type material and a key is given to the genus. PMID- 26287067 TI - Taxonomic study of Chinese species of the genus Macropsis Lewis, 1836 (Hemiptera: Cicadellidae: Macropsinae) II: a new subgenus for Macropsisflavovirens Kuoh. AB - A new monobasic subgenus, Macropsis (Spinoniacropsis) subgen. nov., of the subfamily Macropsinae (Hemiptera: Auchenorrhyncha: Cicadellidae) based on type species Macropsis flavovirens Kuoh, 1992 from Yunnan Province of China is proposed. The new subgenus can be distinguished by the unique character of the male pygofer with two spinelike processes on the caudal margin. Macropsis (S.)flavovirens is redescribed and illustrated, and data on its geographical distribution are given. PMID- 26287068 TI - Cambarus (P) theepiensis, a new species of crayfish (Decapoda:Cambaridae) from the coalfields region of Eastern Kentucky and Southwestern West Virginia, USA. AB - Cambarus (Puncticambarus) theepiensis is a stream-dwelling crayfish that appears to be endemic to the junction of the Cumberland Mountains with the Appalachian Plateau in West Virginia and Kentucky. Within this region, it is prevalent in the Guyandotte and Twelvepole basins of West Virginia, the Little Sandy River and Levisa Fork basins of Kentucky, and tributaries of the Big Sandy River shared by both states. The new species is morphologically most similar to Cambarus robustus and Cambarus sciotensis. It can be differentiated from C. robustus by its broad rostrum, with subparallel, thick-ened margins compared to the narrow, converging rostrum with reduced rostral margins of C. robustus.; larger areola width/length ratio (26 %) than C. robustus (22 %); and mottled color pattern compared to the monotypic color pattern of C. robustus. Canibarus theepiensis can be differentiated from C. sciotensis by the presence of a distinct lateral impression on the chelae compared to the absence of a lateral impression in C. sciotensis; constant thickness of the rostral margin compared to the gradation of rostral thickness in C. sciotensis; greater rostrum width/ length ratio in C. theepiensis (63.1 %) compared to C. sciotensis (57.2 %); and a central projection on the gonopod that is the same length as the mesial process, compared to a central projection that extends past the tip of the mesial process in C. sciotensis. PMID- 26287069 TI - One new species, four new records and key to species of Hydatothrips (Thysanoptera: Thripidae) from China (including Taiwan). AB - Hydatothrips ormosiae sp. n. (Thripidae: Sericothripinae) is described from southern China; H. ekasi, H. liquidambara and H. onari Kudo are newly recorded for mainland China, and H. noro Kudo is newly recorded for Taiwan. A key to the 16 Hydatothrips species recorded from China (including Taiwan) is provided. PMID- 26287070 TI - A new species of Dicranophora Macquart (Diptera, Stratiomyidae) from Bahia State, Brazil and a key to species of the genus. AB - A new species of the Neotropical Dicranophora Macquart is described and illustrated from six males collected in northeast Brazil, Bahia state (Encruzilhada district). Dicranophora femurspiculata sp. nov. is characterized by the specific pattern of spots on the frons, on the legs and on the abdomen, and by a distinct shape of the scutellar process and mid femur A key to the species of the genus and a distribution map are presented. PMID- 26287071 TI - Two new species of Fiorinia Targioni-Tozzetti (Hemiptera: Coccoidea: Diaspididae) from China. AB - The adult females of two new species of armored scale, Fiorinia tianshuiensis Wei & Feng sp. n. and F. dinghuensis Wei & Feng sp. n., are described and illustrated from specimens collected from China. A key is provided for the all Fiorilim species known from China. PMID- 26287072 TI - Scleractinia (Cnidaria: Anthozoa) from ECOMARG 2003, 2008 and 2009 expeditions to bathyal waters off north and northwest Spain (northeast Atlantic). AB - Nineteen species of deep-water scleractinian corals were collected at depths between 488-1222 m during ECOMARG 2003, 2008 and 2009 expeditions to the Avilds Canyon system, Le Danois Bank ('el Cachucho'), and Galicia Bank (northeast Atlantic). Eighteen of them were identified to species. All are previously known from the northeast Atlantic, although several are seldom reported (e.g., Aulocyathus atlanticus, Balanophyllia thalassae, Dendrophyllia alternata, Stephanocyathus crassus). Records of Deltocyathus eccentricus and Flabellum chunii constitute northern range extensions. Six species (Caryophyllia sarsiae, Stephanocyathus crassus, Flabelluin chunii, Flabellun macandrewi, Dendrophyllia alternata, Balanophyllia cellulosa) were recorded outside their previously known bathymetric ranges in the Bay of Biscay and nearby areas. Dendrophyllia alternata, Deltocyathus eccentricus and Stephanocyathus crassus are new to the "West coast of Spain and Portugal" region, here considered of high biodiversity. The bank-building species Lophelia pertusa and Madrepora oculata were abundant on Galicia Bank, and the latter was as well in the Aviles Canyon system. Both were exceedingly rare on Le Danois Bank. Among all species identified, Madrepora oculata was the most common (11 stations). The number of species collected was higher on Le Danois Bank (13 species) than on Galicia Bank (12 species) and in the Aviles Canyon system (3 species), although results may be related to sampling effort. From a literature review and new records presented herein, numbers of species known from each of the three areas total 23, 12, and 18 respectively. PMID- 26287073 TI - A detailed description of Simulium (Meilloniellum) adersi (Pomeroy) from Mayotte, Comoro islands, with comments on bionomics and biogeography (Diptera: Simuliidae). AB - All stages of Simulium (Meilloniellum) adersi (Pomeroy) from Mayotte, Comoro archipelago are described in detail. This species is widespread on the African mainland and in Madagascar; morphological divergences from African material point towards the Mayotte entity being a separate, but closely related species. Biology of the species overall is reviewed and brief comments are made regarding habitats and biogeography of the Mayotte material. PMID- 26287074 TI - Crenicichla gillmorlisi, a new species of cichlid fish (Teleostei: Cichlidae) from the Parana river drainage in Paraguay. AB - Crenicichla gillmorlisi, new species, is described from the rio Acaray, a right bank tributary to the rio Parana. It is most similar to C. mandelburgeri in proportional measurements and meristics, but differs in colour pattern, adults having the body covered with small spots. PMID- 26287075 TI - New species of Nuuanu (Amphipoda: Nuuanuidae) from Norfolk Island, Torres Strait and the Cocos (Keeling) Islands. AB - Three new species of Nuuanu, N. quintalana sp. nov., N. stuckeyorun sp. nov. and N. titaseyi sp. nov. are described from Norfolk Island, Tasman Sea; Cocos (Keeling) Islands, Indian Ocean and the Torres Strait, Australia, respectively. There are currently 17 described species of Nuuanu with the genus distributed world-wide. PMID- 26287076 TI - Teleocichla wajapi, a new species of cichlid from the rio Jari, Brazil, with comments on T. centrarchus Kullander, 1988 (Teleostei: Cichlidae). AB - Teleocichla wajapi, new species, is described from the rio Jari basin, northern Brazil. The new species differs from its congeners by possessing four anal-fin spines, 56-62 scales in El series, smaller orbital diameter (24.6-30.2% of head length) and barred or zigzag color pattern on flanks. New information on the morphology and distribution of T. centrarchus is provided based on recently collected material. PMID- 26287078 TI - Chilocoris nitidus Mayr, 1865, the first Oriental burrower bug recorded in Tajikistan, with remarks on the zoogeography of the nitidus-group of Chilocoris Mayr, and an annotated checklist of Tajik Cydnidae (Hemiptera: Heteroptera). PMID- 26287077 TI - A new subgenus and species of the genus Hedyphanes Fischer von Waldheim, 1820 (Coleoptera: Tenebrionidae: Helopini) from Israel and Egypt. AB - A new species, Hedyphanes chikatunovi sp. n., is described from southern Israel (Negev, Gerofit) and Egypt (Northern Sinai). These localities represent the southwestern limit of the distribution of the genus. The new species is placed in a new monotypic subgenus, Microhedyphanes subgen. n. PMID- 26287079 TI - First record of the moray eel Gymnothorax reticularis, Bloch, 1795 in the Mediterranean Sea, with a note on its taxonomy and distribution. AB - The first Red-Sea Indo-Pacific alien moray eel in the Eastern Mediterranean is reported here. A single specimen ot Gymnothorax reticularis was captured by a commercial bottom-trawl vessel off the northern coast of Israel. Morphological and anatomical similarities with the single known Red-Sea specimen raise an old taxonomic dilemma. PMID- 26287080 TI - Revision of the Subgenus Coprochara Mulsant & Rey of the Genus Aleochara Gravenhorst from Japan (Coleoptera: Staphylinidae: Aleocharinae). AB - A taxonomic revision of the subgenus Coprochara Mulsant & Rey, 1874 of the genus Aleochara Gravenhorst, 1802 in Japan is presented. The following three species are recognized: Aleochara (C.) verna Say, 1833, A. (C.) binotata Kraatz, 1856 and A. (C.) squalithorax Sharp, 1888, of which A. binotata is new to Japan. All previous records of "A. (C.) bipustulata (Linnaeus, 1760)" should be regarded as misidentifications of eitherA. verna orA. binotata. New records are added for, A. squalithorax, a littoral species. All species are redescribed, figured, keyed and mapped. PMID- 26287081 TI - Four new species of Aphelinidae (Hymenoptera: Chalcidoidea) from Mexico. AB - Four new species of Encarsia Forster (Hymenoptera: Aphelinidae) from Mexico are described--E. albata Myartseva sp. n. (State of Nuevo Leon), E. barracas Myartseva sp. n. (State of Baja California Sur), E. chichenitza Myartseva sp. n. (State of Yucatan) and E. elenae Myartseva sp. n. (State of Tamaulipas). A key to the species of Encarsia in Mexico published in 2012 is modified to include the newly described species. PMID- 26287082 TI - Lymnastis of Ukraine with the redescription of Lymnastis novikovi (Coleoptera: Carabidae). AB - The rare species Lymnastis novikovi Michailov, 1998, described from the single female specimen collected in Ukraine, is redescribed on the basis of new material. We provide the illustrations of the general habitus, the median lobe and its internal sac and describe the habitat of L. novikovi, to increase information about this species. A key to European Lyinastis species is given. The current distribution of Lymnastis galilaeus Piochard de la Brulerie, 1876 and L. novikovi in Ukraine is described. PMID- 26287083 TI - New and little known Brachodidae from tropical Asia and Papua New Guinea (Lepidoptera, Cossoidea). AB - In this study nine new species and a new genus of Brachodidae are described from tropical Asia and Papua New Guinea. Synechodes polias sp. nov. and Synechodes tamila sp. nov. are described from Sulawesi and southern India, respectively. A new genus, Saccocera gen. nov. (type species Miscera orpheus Kallies, 2004), is described to accommodate five species occurring from Taiwan and Sumatra across Melanesia to Papua New Guinea. It differs significantly from the related genera Miscera Walker, 1863 and Synechodes Turner, 1913 in morphological details of the head and the male and female genitalia. Two species of Saccocera are described here, Saccocera panaras sp. nov. from Papua New Guinea and Saccocera miangkabau sp. nov. from Sumatra. Furthermore, Miscera minahasa sp. nov. and Paranigilgia mariannae sp. nov. are described from Sulawesi, Paranigilgia brandti sp. nov. and Nigilgia atribractea sp. nov. from Papua, and Nigilgia browni sp. nov. is described from Christmas Island. Finally, Synechodes heppneri Kallies, 1998 syn. nov. is reverted to a junior synonym of Synechodes coniophora Turner, 1913. Nigilgia anactis Diakonoff, 1982 is figured for the first time and its distribution in Asia is discussed. PMID- 26287084 TI - Bregmosina, a new Neotropical genus of Limosininae (Diptera: Sphaeroceridae). AB - Bregmosina, a new genus of Limosininae (Diptera, Sphaeroceridae), is described on the basis of five new species from Central and South America. The genus is characterized by a broad head, swollen face, large oral cavity, a single pair of very large cruciate interfrontal bristles, short, broad fore tarsomeres and swollen hind tarsomeres one and two. The unusual male genitalia, including a longitudinally split sternite 5, strongly indicate that the genus is monophyletic. All species are probably associated with treefalls. PMID- 26287085 TI - From a dwarf to a giant: Revalidation of Callulops valvifer (Barbour, 1910), (Amphibia, Anura, Microhylidae). AB - According to the most recent revision of the subfamily Asterophryinae, the species Pomatops valvifera was considered to be a synonym of Phrynomantis (now Callulops) robusta. On the basis of recently collected material from near the type locality of Pomatops valvifera on the Bomberai Peninsula in western New Guinea, the invalidity of the genus name is confirmed but the species name is revalidated. Callulops valvifer (new combination) was hitherto unequivocally known from a single specimen of less than 30 mm snout-vent length. With a length of more than 70 mm for males and of more than 80 mm for females, this species is now among the largest of the currently known 22 species of the genus Callulops. PMID- 26287086 TI - Morphology and Postdepositional Dynamics of Eggs of the Predator Podisus distinctus (Stal) (Heteroptera: Pentatomidae: Asopinae). AB - The predator Podisus distinctus (Stal) (Heteroptera: Pentatomidae: Asopinae) has been reared to control lepidopteran defoliators. In this study, we describe this predator's morphology, postdepositional dynamics and eggs in different developmental stages under scanning electron microscope. Its eggs are subglobular and ovoid, narrower at the base than at the top, with a convex, circular operculum. They measure 1.09+/-0.03 mm in height and 0.90+/-0.04 mm in diameter. The aero-micropylar processes number 16.00+/-2.00 and are arranged radially at the egg anterior pole. Immediately after laying, the egg color is pearl-like, and soon after turns gray. Orientation of the spine-like projections and aero micropylar processes also change after deposition. Though the eggs of P. distinctus are similar to those of other species of the genus Podisus, certain aspects, including the egg size and shape, chorion micro-sculptures, and number of aero-micropylar processes, are specific, allowing for differentiation from other related species. PMID- 26287087 TI - Metopa gigas sp. nov. from southern Greenland, a giant among congeners (Crustacea, Amphipoda, Stenothoidae). AB - Metopa gigas sp. nov. is described from southern Greenland (east and west). This new species which reaches a length of around 20 mm is, together with M. mirifica Gurjanova, 1948 from the North Pacific, by far the largest member of the genus. The species is easily separated from sympatric Metopa clypeata (Kroyer, 1842; 15 mm; type species of Metopa) with which it has been confused, by small saddle-like ornaments dorsally on pereonites, and much longer antenna 1. It can be distinguished from Metopa mirifica by the simple propodus of gnathopod 1, whereas that of M. mirifica is strongly subchelate. PMID- 26287088 TI - DNA-sequence data require revision of the parrot genus Aratinga (Aves: Psittacidae). PMID- 26287089 TI - An annotated catalog of the Iranian Dipsocoromorpha, Enicocephalomorpha, Gerromorpha, Leptopodomorpha and Nepomorpha (Hemiptera: Heteroptera). AB - A catalog of aquatic and semiaquatic Heteroptera from Iran is provided based on literature reports and field collections. Representatives of 107 species and morphospecies of the infraorders Dipsocoromorpha, Enicocephalomorpha, Gerromorpha, Leptopodomorpha, and Nepomorpha are listed, and are distributed in 18 families including Aphelocheiridae (1 genus, 1 species), Belostomatidae (1 genus, 1 species), Corixidae (8 genera, 29 species), Dipsocoridae (1 genus, 2 species), Enicocephalidae (2 genera, 2 species), Gerridae (6 genera, 18 species), Hebridae (1 genus, 5 species), Helotrephidae (1 genus, 1 species), Hydrometridae (1 genus, 2 species), Leptopodidae (4 genera, 7 species), Mesoveliidae (1 genus, 2 species), Naucoridae (1 genus, 1 species), Nepidae (3 genera, 5 species), Notonectidae (2 genera, 8 species), Ochteridae (1 genus, 1 species), Pleidae (1 genus, 1 species), Saldidae (5 genera, 14 species), and Veliidae (2 genera, 7 species). Synonyms and geographical distribution of all the species are given, together with an identification key of families. According to the actual catalogs and studies eight species are doubtful for Iranian fauna. PMID- 26287090 TI - Trans-Andean Ancistrus (Siluriformes: Loricariidae). AB - We review the trans-Andean species of Ancistrus from Panama, Colombia and Venezuela. Based on analyses of meristic, morphometric and pigmentation pattern data of preserved specimens, eight of sixteen species reported from this region are considered valid and two new species are described. Here we review Ancistrus chagresi Eigenmann & Eigenmann 1889 from both slopes of central Panama; A. centrolepis Regan 1913 from Pacific slopes of eastern Panama and western Colombia; Ancistrus caucanus Fowler 1943, from the Magdalena River drainage in northern Colombia; Ancistrus martini Schultz 1944, from the Lake Maracaibo Basin of Venezuela and Colombia. Ancistrus galani Perez & Viloria 1994, from a cave in the Lake Maracaibo Basin of Venezuela is considered valid but was not examined. Ancistrus tolima new species is described from the upper Magdalena River drainage and Ancistrus vericaucanus new species is described from the upper Cauca River drainage. Ancistrus gymnorhynchus Kner 1854 and A. falconensis Taphorn, Armbruster & Rodriguez-O. 2010 were treated previously. One specimen of A. clementinae Rendahl 1937 from the Pacific coast of Ecuador was examined, it is considered a valid species. A key for identification and geographical ranges are provided. PMID- 26287091 TI - A new species of Ceratophysella (Collembola: Hypogastruridae) from Japan, with notes on its DNA barcode and a key to Japanese species in the genus. AB - Ceratophysella comosa sp. nov. was collected from ascomata of Ciborinia canielliae in Japan and the morphological and molecular characteristics of the species are described here. The species has 3 + 3 cephalic spines as in Ceratophysella loricata and Ceratophysella pilosa, but a plurichaetosis intermediate between C. loricata (absent) and C. pilosa (strong). The new species can be distinguished from these two species also by the number of setae on the first thorax segment and ventral tube. Partial DNA sequences of the mitochondrial cytochrome c oxidase subunit 1 (COI) gene were used as DNA barcodes to distinguish species. Interspecific genetic distances of the gene were higher than the intraspecific distances between Ceratophysella species for which sequence data are available. An identification key of Japanese Ceratophysella is provided. PMID- 26287092 TI - A new species of the genus Promacrolaelaps (Acari: Laelapidae) associated with Propomacrus bimucronatus (Pallas) (Coleoptera: Scarabaeidae) in Iran. AB - We describe a new species of mite from Iran - Pronacrolaelaps propomacrus sp. nov. (Acari: Laelapidae). The new species was collected in association with the beetle Propomacrus bimucronatus (Pallas) (Coleoptera: Scarabaeidae: Euchirinae) in holes in the trunk of oak trees. The genus Promacrolaelaps is redescribed and distinguished from the related genus Hypoaspis Canestrini sells. strict. PMID- 26287093 TI - Holothuria (Semperothuria) roseomaculata n. sp. (Aspidochirotida: Holothuriidae), a coral-reef inhabiting sea cucumber from the western Pacific Ocean. AB - Holothuria (Semperothuria) roseomaculata n. sp. is described from the main islands of Yap, Federated States of Micronesia. The ossicles are similar to those of its sister species, the sympatric H. (S.) flavomaculata Semper, 1868, but the new species is easily recognised, both in the field and among preserved specimens, by its much larger, rose-coloured dorsal papillae that fade to white in alcohol. Holothuria (S.) roseomaculata n. sp. appears to be an endemic of the tropical westernmost Pacific Ocean; it has been recorded from Okinawa to New Caledonia. PMID- 26287094 TI - External morphology, chondrocranium, hyobranchial skeleton, and external and internal oral features of Rhinoderma rufum (Anura, Rhinodermatidae). PMID- 26287095 TI - On some mites (Acari: Prostigmata) from the Interior Highlands: descriptions of the male, immature stages, and female reproductive system of Pseudocheylus americanus (Ewing, 1909) and some new state records for Arkansas. AB - The male and immature stages of Pseudocheylus americanus (Ewing, 1909) (Pseudocheylidae) are described and illustrated for the first time and the female is re-illustrated. The description of Pseudobonzia reticulata (Heryford, 1965) (Cunaxidae) is modified to include the presence of dorsal setae f2, which were not reported in the original description. In addition, Bonzia yunkeri Smiley, 1992 and Parabonzia bdelliforimis (Atyeo, 1958) (Cunaxidae) are reported from the Ozark Mountains, Caeculus cremnicolus Enns, 1958 (Caeculidae) is reported from the Ozark and Ouachita Mountains, and Dasythyreus hirsutus Atyeo, 1961 (Dasythyreidae) is reported from Missouri and the Ouachita Mountains in Arkansas. PMID- 26287096 TI - On the identity of Clistocoeloma balansae A. Milne-Edwards, 1873, and C. tectum (Rathbun, 1914), with description of a new species from the West Pacific (Crustacea: Decapoda: Sesarmidae). AB - The identity of the mangrove sesarmid crab Clistocoeloma balansae A. Milne Edwards, 1873, is clarified on the basis of the types from New Caledonia, and fresh material from Vanuatu and the Philippines. Sesarma (Sesarma) tectum Rathbun, 1914, is shown to be a junior subjective synonym of C. balansae A. Milne Edwards, 1873. A new species, C. melanesicum, superficially similar to C. balansae, is described from Vanuatu, New Caledonia, and, Solomon Islands. PMID- 26287097 TI - The taxonomic status of Oligoryzomys brendae Massoia, 1998 (Rodentia, Cricetidae), with comments on the availability of this name. AB - Oligoryzomys brendae was poorly described by Massoia in 1998 to include populations of the large form of Oligoryzomys that inhabits the Yungas and high altitudinal grasslands of northwestern Argentina, which were previously referred as O. longicaudatus, O. stolzmanni, O. destructor or Oligoryzomys sp. Contrary to some interpretations, we state that the name O. brendae is available, given that it fully accomplishes the requirements of the International Code of Zoological Nomenclature. We also present morphologic and genetic evidence showing that this taxon represents a distinct species and provide an emended diagnosis and re description of it. In addition, the evidence at hand indicates that O. brendae is the only large-sized species of Oligoryzomys inhabiting northwestern Argentina. PMID- 26287098 TI - Subfossils of extinct and extant species of Simuliidae (Diptera) from Austral and Cook Islands (Polynesia): anthropogenic extirpation of an aquatic insect? AB - Subfossil head capsules of Simuliidae larvae have been recovered from swamps on Tubuai and Raivavae of the Austral Islands, and Atiu and Mangaia of the southern Cook Islands. For Tubuai and Raivavae it is likely that the simuliids are extinct, but a single simuliid species is extant on nearby Rurutu. For Atiu and Mangaia, extant simuliids have not been reported, but are known on Rarotonga. Well-preserved head capsules indicate that the Cook Islands subfossils are those of Sinulitin (Inseliellumn) teruananga Craig and Craig, 1986. For the Austral Islands, the simuliid from Tubuai is considered a variant of Simudiunt (Inseliellumn) rurutuense Craig and Joy, 2000. That from Raivavae is morphologically distinct and is described here as a new species, Simuliun (Inseliellumn) raivavaense Craig and Porch. Humans arrived in Eastern Polynesia ca. 1,000 years ago resulting in the widespread destruction of lowland forest and conversion of wetlands to agriculture with implied consequences for the indigenous biota of these habitats. Here we consider that one such result was loss of freshwater aquatic biodiversity. PMID- 26287099 TI - Description of a new genus and species of the family Melphidippidae Stebbing, 1899 (Crustacea: Amphipoda) from the deep waters of Brazil. AB - The species of the amphipod family Melphidippidae are distributed worldwide in marine habitats, but there is no record of this family from Brazil so far. A new genus and species of Melphidippidae are described from Brazilian waters. Stebbingiella gen. nov. is monotypic and is distinguished from the other genera of the family by the presence of: antenna 1 with accessory flagellum 7 articulate, lateral cephalic lobe subacute, with globular eyes extremely produced, reaching beyond the second article of peduncle of antenna 2; gnathopods stout and slightly subchelate; coxae 3 and 4 with strong anterior projection and coxae 5 and 7 with strong posterior projection; telson cleft, not fully movable, with two globular lobes, about 2X wider than long. Stebbingiella globulosa sp. nov. is the first species of Melphidippidae recorded from Brazilian waters. PMID- 26287100 TI - First record of the genus Megalota Diakonoff from China, with the descriptions of two new species (Lepidoptera: Tortricidae: Olethreutinae). AB - Megalota Diakonoff, 1966 is reported from China for the first time. Two new species, M. bicepsunca, sp. nov., and M., curvativa, sp. nov., are described and illustrated based on the male adults, both of them are distributed in south China Photographs of the adults and male genitalia are provided. PMID- 26287101 TI - Two new species of the genus Paramitraceras Pickard-Cambridge, 1905 (Opiliones: Laniatores: Stygnopsidae) from Chiapas, Mexico. AB - Parainitraceras pickardcanibridgei sp. nov. and Paramitraceras tzotzil sp. nov. from Chiapas, Mexico are described based on specimens previously determined as Paramitraceras granulatum Pickard-Cambridge, 1905 by Goodnight and Goodnight. The male genitalia of the new species and P. granulatum are illustrated with scanning electronic micrographs (SEMs) or drawings derived from them. The importance of the ocular tubercle, cheliceral dentition and sexual dimorphism, pedipalpal armature and male genitalia as taxonomic characters within the genus is discussed as well as differences and similarities between Paramitraceras Pickard-Cambridge, 1905 and its most similar genus, Sbordonia Silhavy, 1977. PMID- 26287102 TI - Larval morphology of the antlion Myrmecaelurus trigrammus (Pallas, 1771) (Neuroptera, Myrmeleontidae), with notes on larval biology. AB - Morphology and behaviour of third instar larvae of the Holomediterranean antlion species Myrmecaelurus trigranunus (Pallas) are described. Larvae are facultative pit-builders, they either ambush their prey at the surface, or dig pitfall traps that prey fall in to. Dark brown spots on dorsal and ventral sides of the head and on dorsal side of the thorax are characteristic of the larvae. Eye tubercles are not prominent. Jaws are equipped with long bristles, campaniform sensilla, sensilla coeloconica, and digitiform sensilla. A unique feature is the shape of the tips of all three teeth that is screw-like with a polyhedral surface. The body surface is covered with longitudinally grooved bristles and plumose hairs. On the tip of the antennae and on terminal and subterminal parts of labial palps sensilla basiconica occur. On the 9th abdominal segment there are two bulges, each of them bearing four digging bristles. Non-prominent eye tubercles and numerous mandibular bristles are morphological traits of pit-builders. Most of the behavioural traits are related to pit builders, whereas forward movement, waiting for prey without a pit and frequent changing of ambush location are traits of non-pit builders. PMID- 26287103 TI - A new species and new distribution records for Braconidae from Mountain Lake Biological Station in southwestern Virginia and a redescription of Pentapleura foveolata Viereck. AB - One new species of Alysiinae, Coelinius wrayi Kula, is described. Pentapleurafoveolata Viereck, also in Alysiinae and previously known only from a male collected at the type locality in Connecticut, is redescribed based on six females and two males collected at Mountain Lake Biological Station (MLBS) in Virginia. Morphological variation for Alysia (Alysia) salebrosa Wharton is discussed given variation observed in specimens from MLBS. Sixty-two species of Braconidae collected at MLBS in August of 2009 are listed along with 12 species reported previously from MLBS. Host use for the 62 species is discussed; 31 are in Alysiinae or Opiinae, subfamilies that exclusively contain parasitoids of cyclorrhaphous flies. Fifteen species are reported from Virginia for the first time. Problematic couplets in a key to species of Spathius Nees for North America (Marsh & Strazanac 2009) are discussed using specimens from MLBS. PMID- 26287104 TI - Epinephelus geoffroyi (Klunzinger, 1870) (Pisces: Serranidae), a valid species of grouper endemic to the Red Sea and Gulf of Aden. AB - The grouper Epinephelus geoffioyi (Klunzinger), type locality Red Sea, previously regarded as a synonym of E. chlorostigma (Valenciennes) is recognized as a valid species. It is differentiated from E. chlorostigma by having 25-29 (modally 27) gill rakers vs. 23-26 (modally 24), a more angular anal fin, the dark spots on the abdomen more widely separated, and lacking a clear white margin posteriorly on the caudal fin. The missing holotype of E. geoffroyi was found at the Staatliches Museum fur Naturkunde Stuttgart (SMNS 233, 191 mm). Epinephelits chlorostigma is wide-ranging from the Gulf of Aden and east coast of Africa to Samoa; it is reported from the depth range of 32-280 m. Epinephelus geoffroyi is presently known only from the Red Sea and Gulf of Aden at depths of 3-32 m. Illustrations are provided for three other species of groupers with numerous small dark spots, E. areolatus (Forsskal), E. gabriellae Randall & Heemstra, and E. polylepis Randall & Heemstra, that are, or might be, sympatric with E. geoffroyi. PMID- 26287105 TI - Taxonomic review of Chinese Phalonidia Le Marchand, 1933 (Lepidoptera: Tortricidae: Cochylini). AB - The Chinese species of Phalonidia Le Marchand, 1933 are reviewed. Sixteen species and one subspecies are treated, including three new species (P. brevifasciaria, sp. nov., P. rotundiventralis, sp. nov., and P. tenuispinifornis, sp. nov.) and three newly recorded species or subspecies (P. affinitana tauriana (Kennel, 1899), P. aliena Kuznetzov, 1966, and P. coreana Byun & Li, 2006). The female of P. lydiae (Filipjev, 1940) is described for the first time. Images of adults and genitalia are provided, along with a key and a distribution map for the genus in China. PMID- 26287106 TI - New species and records of quill mites of the family Syringophilidae (Acari: Prostigmata) from the passerines (Aves: Passeriformes) from the Russian Far East. AB - Two new species, Syringophilopisis pari sp. nov. from Poecile palustris Linnaeus (Paridae) and Torotrogla volgini sp. nov. from Emberiza elegans Temminck (Emberizidae) are described. Additionally, new host species are reported for three syringophilid species: Emberiza tristrami Swinhoe and E. rutila Pallas for Betasyringophiloidus schoeniclus (Skoracki); Sitta europaea Linnaeus (Sittidae) for Syringophilopsis sittae Skoracki et al., and Zosterops erythropleurus Swinhoe (Zosteropidae) for Neoaulonastus zosterops Skoracki et al. All avian hosts were captured in the Primorsky Krai, Russia. The syringophilid fauna presently recorded from Russia is summarized. PMID- 26287107 TI - Three new species of the genus Sternoppia (Acari: Oribatida: Sternoppiidae) from Ecuador. AB - Three new oppioid mite species of the genus Sternoppia, S. paraincisa sp. nov., S. paramirabilis sp. nov. and S. fissurata sp. nov., are described. Sternoppia paraincisa sp. nov. is most similar morphologically to Sternoppia incisa Balogh & Mahunka, 1977 from Bolivia, however, it differs from the latter by smaller body size, presence of notogastral setae c, location of lyrifissures ia, presence of granules on anal plates, and setiform sensilli. Sternoppia paramirabilis sp. nov. is most similar morphologically to Sternoppia mirabilis Balogh & Mahunka, 1968 from Argentina, however it differs from the latter by larger body size, presence of two or three sensillar branches only, and long interlamellar setae. Sternoppia fissurata sp. nov. differs from all species of the genus by the nine pairs of notogastral setae, location of lyrifissures iad in inverse apoanal position, and the presence of large tectum on anterior part of ventral plate. Sternoppia brasiliensis is for the first time recorded in Ecuador. An identification key to all known species of Sternoppia is provided. PMID- 26287108 TI - Karyological and meiotic studies in seven species of Coreinae (Hemiptera: Heteroptera: Coreidae) from North India. AB - Coreinae, the largest subfamily of Coreidae, is distributed worldwide but is most abundant in the tropics. Cytogenetic data is available for 122 species, which include 40 from India. In the present paper, 7 species of Coreinae have been cytogenetically investigated for the first time for their diploid chromosome complement and for meiosis. Also, this is the first cytogenetic report for the genera Prionoloinia and Petalocnemis. The modal diploid chromosome complement of the family Coreidae is 2n=21=18A+2m+X0. The present study on 7 species shows the diploid chromosome complement to vary from 15 to 27. Microchromosomes are present in 6 and absent only in I species. The sex determining mechanism is X0 in 5 and X1X20 in 2 species. The decrease in autosome number (14A) has been accompanied by 2 pairs of extremely large autosomes (Anoplocienis binotata Distant and Cletus borealis Blote) and the increase in autosome number (22A, 24A) has been accompanied by distinctly small autosomes (Petalocnemis obscura and Prionolomia sp.) in the complement. The behavior of chromosomes during meiosis is typical of Coreidae. Deviations wherever recorded are discussed. During diplotene, chiasmata are located terminally and there is a predominance of a single chiasma per bivalent. However, in Anoplocnemis binotata and Cletus borealis, one or both of the large bivalents show two terminal or subterminal chiasmata in diplotene. A regular arrangement of chromosomes is observed during both metaphase I and II: all the autosomes form a ring with microchromosomes lying inside and sex chromosomes lying outside the ring. PMID- 26287109 TI - Implementation as theory, hierarchy as transformation, homology as synapomorphy. AB - Presently cladistics is based on, and justified by, a computer implementation (Wagner Parsimony) rather than sound methodological or theoretical foundations. In this paper, the recent goals of cladistics that are derived from computer implementations and 'tree-thinking' are discussed. The discussion raises a critical point, namely whether one can dispense with these recent goals and adopt a wholly systematic approach, one herein termed systematic thinking. PMID- 26287110 TI - Two new species and a new genus of Calloporidae (Bryozoa: Cheilostomata) from the Southwest Atlantic. AB - The family Calloporidae occupies a basal position in the classification of the Cheilostomata, the relatively simple calloporid morphology seeming to be the basic pattern for the adaptive radiation of cheilostome bryozoans. The ovicells of the Calloporidae may be formed by the maternal zooid or the distal zooid, which can be an autozooid, a vicarious avicularium or a kenozooid. Examination of new calloporid material from the southern Patagonian shelf revealed the existence of two new species and a new genus. Kenoaplousinafissurata gen. nov., sp. nov. is characterized by its distinctive kenozooidal ooecium. The new genus is also deemed to include Aplousina grandipora Moyano, an allied species from the Chilean continental slope. Alderina simplicissima sp. nov., is also described from the Magellanic region. PMID- 26287111 TI - FORENSIC SCIENCE AROUND THE WORLD. PMID- 26287112 TI - NIST Forensic Science Research Update. PMID- 26287113 TI - The Forensic Technology Center of Excellence--Recent and Upcoming Activities. PMID- 26287114 TI - 20th Scientific Meeting of the Society of Hair Testing. PMID- 26287115 TI - FORENSIC SCIENCE EDUCATIONAL PROGRAMS--United Kingdom (UK) & Ireland. PMID- 26287116 TI - [RECOPANC Study: no difference between pancreatogastrostomy and pancreatojejunostomy of clinically significant pancreatic fistulas]. PMID- 26287117 TI - [First randomized study on prophylactic lymph node dissection in papillary thyroid carcinoma]. PMID- 26287118 TI - [It is not always gout! : A rare diagnosis of troublesome tumors on fingers and toes]. PMID- 26287119 TI - Facet shapes and thermo-stabilities of H2SO4*HNO3 hydrates involved in polar stratospheric clouds. AB - The nucleation, ice crystal shapes and thermodynamic stability of polar stratospheric clouds particles are interesting concerns owing to their implication in the ozone layer destruction. Some of these particles are formed by conformers of H2O, HNO3, and H2SO4. We carried out calculations using density functional theory (DFT) to obtain optimized structures. Several stable trimers are achieved -divided in two groups, one with HNO3 moiety, second with H2SO4 moiety- after pre-optimization at B3LYP/6-31G and subsequently optimization at B3LYP/aug-cc-pVTZ level of theory. For both most stable conformers five H2O molecules are added to their optimized trimers to calculate hydrated geometries. The OH stretching harmonic frequencies are provided for all aggregates. The zero point energy correction (ZEPC), relative electronic energies (?E), relative reaction Gibbs free energies ?(?G)k-relative, and cooling constant (K cooling ) are reported at three temperatures: 188 K, 195 K, and 210 K. Shapes given in our calculations are compared with various experimental shapes as well as comparisons with their thermo-stabilities. PMID- 26287120 TI - Coil-Type Asymmetric Supercapacitor Electrical Cables. AB - Cable-shaped supercapacitors (SCs) have recently aroused significant attention due to their attractive properties such as small size, lightweight, and bendability. Current cable-shaped SCs have symmetric device configuration. However, if an asymmetric design is used in cable-shaped supercapacitors, they would become more attractive due to broader cell operation voltages, which results in higher energy densities. Here, a novel coil-type asymmetric supercapacitor electrical cable (CASEC) is reported with enhanced cell operation voltage and extraordinary mechanical-electrochemical stability. The CASECs show excellent charge-discharge profiles, extraordinary rate capability (95.4%), high energy density (0.85 mWh cm(-3)), remarkable flexibility and bendability, and superior bending cycle stability (~93.0% after 4000 cycles at different bending states). In addition, the CASECs not only exhibit the capability to store energy but also to transmit electricity simultaneously and independently. The integrated electrical conduction and storage capability of CASECS offer many potential applications in solar energy storage and electronic gadgets. PMID- 26287121 TI - Catalyst-Controlled, Regioselective Reactions of Carbohydrate Derivatives. AB - Carbohydrates generally possess multiple hydroxyl groups of similar reactivity, and selective monofunctionalization is often difficult. Catalysis provides a versatile and potentially general solution to this problem. This chapter provides an overview of catalyst-controlled methods for the regioselective activation of carbohydrate derivatives. The catalysts discussed include organocatalysts (Lewis bases, Bronsted acids/bases, and others) as well as those based on main group and transition metal elements. PMID- 26287122 TI - Rearrangements Induced by Hypervalent Iodine. AB - This chapter describes advances in hypervalent iodine(III)-induced rearrangements reported between 2004 and 2015, beginning with Hofmann-type rearrangements and aliphatic aryl transpositions. In both reactions the iodine(III) reagent may be off-the-shelf or catalytically generated in situ. A number of stereoselective transformations are discussed, followed by transpositions triggered through phenol dearomatization, including Wagner-Meerwein-type rearrangements, Prins pinacol transpositions, and a tandem polycylization-pinacol process. Other rearrangements such as an iodonio-Claisen rearrangement, an ipso-rearrangement, and rearrangements performed using iodine(V) are also described. PMID- 26287123 TI - Supersymmetry in quantum optics and in spin-orbit coupled systems. AB - Light-matter interaction is naturally described by coupled bosonic and fermionic subsystems. This suggests that a certain Bose-Fermi duality is naturally present in the fundamental quantum mechanical description of photons interacting with atoms. We reveal submanifolds in parameter space of a basic light-matter interacting system where this duality is promoted to a supersymmetry (SUSY) which remains unbroken. We show that SUSY is robust with respect to decoherence and dissipation. In particular, the stationary density matrix at the supersymmetric lines in parameter space has a degenerate subspace. The dimension of this subspace is given by the Witten index and thus is topologically protected. As a consequence, the dissipative dynamics is constrained by a robust additional conserved quantity which translates information about an initial state into the stationary state. In addition, we demonstrate that the same SUSY structures are present in condensed matter systems with spin-orbit couplings of Rashba and Dresselhaus types, and therefore spin-orbit coupled systems at the SUSY lines should be robust with respect to various types of disorder. Our findings suggest that optical and condensed matter systems at the SUSY points can be used for quantum information technology and can open an avenue for quantum simulation of SUSY field theories. PMID- 26287124 TI - Minimal sample requirement for highly multiplexed protein quantification in cell lines and tissues by PCT-SWATH mass spectrometry. AB - The amount of sample available for clinical and biological proteomic research is often limited and thus significantly restricts clinical and translational research. Recently, we have integrated pressure cycling technology (PCT) assisted sample preparation and SWATH-MS to perform reproducible proteomic quantification of biopsy-level tissue samples. Here, we further evaluated the minimal sample requirement of the PCT-SWATH method using various types of samples, including cultured cells (HeLa, K562, and U251, 500 000 to 50 000 cells) and tissue samples (mouse liver, heart, brain, and human kidney, 3-0.2 mg). The data show that as few as 50 000 human cells and 0.2-0.5 mg of wet mouse and human tissues produced peptide samples sufficient for multiple SWATH-MS analyses at optimal sample load applied to the system. Generally, the reproducibility of the method increased with decreasing tissue sample amounts. The SWATH maps acquired from peptides derived from samples of varying sizes were essentially identical based on the number, type, and quantity of identified peptides. In conclusion, we determined the minimal sample required for optimal PCT-SWATH analyses, and found smaller sample size achieved higher quantitative accuracy. PMID- 26287125 TI - Brain and behavioral inhibitory control of kindergartners facing negative emotions. AB - Inhibitory control (IC) - one of the most critical functions underlying a child's ability to self-regulate - develops significantly throughout the kindergarten years. Experiencing negative emotions imposes challenges on executive functioning and may specifically affect IC. In this study, we examined kindergartners' IC and its related brain activity during a negative emotional situation: 58 children (aged 5.5-6.5 years) performed an emotion-induction Go/NoGo task. During this task, we recorded children's performance and brain activity, focusing on the fronto-central N2 component in the event-related potential (ERP) and the power of its underlying theta frequency. Compared to Go trials, inhibition of NoGo trials was associated with larger N2 amplitudes and theta power. The negative emotional experience resulted in better IC performance and, at the brain level, in larger theta power. Source localization of this effect showed that the brain activity related to IC during the negative emotional experience was principally generated in the posterior frontal regions. Furthermore, the band power measure was found to be a more sensitive index for children's inhibitory processes than N2 amplitudes. This is the first study to focus on kindergartners' IC while manipulating their emotional experience to induce negative emotions. Our findings suggest that a kindergartner's experience of negative emotion can result in improved IC and increases in associated aspects of brain activity. Our results also suggest the utility of time-frequency analyses in the study of brain processes associated with response inhibition in young children. PMID- 26287127 TI - Alphavirus capsid proteins self-assemble into core-like particles in insect cells: A promising platform for nanoparticle vaccine development. AB - The mosquito-borne chikungunya virus (CHIKV) causes arthritic diseases in humans, whereas the aquatic salmonid alphavirus (SAV) is associated with high mortality in aquaculture of salmon and trout. Using modern biotechnological approaches, promising vaccine candidates based upon highly immunogenic, enveloped virus-like particles (eVLPs) have been developed. However, the eVLP structure (core, lipid membrane, surface glycoproteins) is more complex than that of non-enveloped, protein-only VLPs, which are structurally and morphologically 'simple'. In order to develop an alternative to alphavirus eVLPs, in this paper we engineered recombinant baculovirus vectors to produce high levels of alphavirus core-like particles (CLPs) in insect cells by expression of the CHIKV and SAV capsid proteins. The CLPs localize in dense nuclear bodies within the infected cell nucleus and are purified through a rapid and scalable protocol involving cell lysis, sonication and low-speed centrifugation steps. Furthermore, an immunogenic epitope from the alphavirus E2 glycoprotein can be successfully fused to the N terminus of the capsid protein without disrupting the CLP self-assembling properties. We propose that immunogenic epitope-tagged alphavirus CLPs produced in insect cells present a simple and perhaps more stable alternative to alphavirus eVLPs. PMID- 26287126 TI - Aldosterone induces clonal beta-cell failure through glucocorticoid receptor. AB - Aldosterone excess causes insulin resistance in peripheral tissues and directly impairs the function of clonal beta-cell. The aim of this study was to investigate the molecular mechanisms involved in the aldosterone-induced impairment of clonal beta-cells. As expected, aldosterone induced apoptosis and beta-cell dysfunction, including impairment of insulin synthesis and secretion, which were reversed by Glucocorticoid receptor (GR) antagonists or GR-specific siRNA. However, mineralocorticoid receptor (MR) antagonists or MR-specific siRNA had no effect on impairment of clonal beta-cells induced by aldosterone. Besides, aldosterone significantly decreased expression and activity of MafA, while activated JNK and p38 MAPK in a GR-dependent manner. In addition, JNK inhibitors (SP600125) and/or p38 inhibitors (SB203580) could abolish the effect of aldosterone on MafA expression and activity. Importantly, overexpression of JNK1 or p38 reversed the protective effect of a GR antagonist on the decrease of MafA expression and activity. Furthermore, aldosterone inhibits MafA expression at the transcriptional and post-transcriptional level through activation of JNK and p38, respectively. Consequently, overexpression of MafA increased synthesis and secretion of insulin, and decreased apoptosis in clonal beta-cells exposed to aldosterone. These findings identified aldosterone as an inducer of clonal beta cell failure that operates through the GR-MAPK-MafA signaling pathway. PMID- 26287129 TI - New Polyprenylated Phloroglucinol and Other Compounds Isolated from the Fruits of Clusia nemorosa (Clusiaceae). AB - Clusia nemorosa has been widely used in folk medicine to treat various ailments, including headaches and inflammation. Investigation of the fruits of Clusia nemorosa (Clusiaceae) led to the isolation and characterization of a new phloroglucinol derivative, named 6S,8S,28S-nemorosic acid (1), together with seven known compounds: friedelin (2), beta-sitosterol (3), stigmasterol (4), beta sitosterol glycoside (5), kaempferol (6), quercetin (7) and dimethyl citrate (8). The structures were determined by extensive 1D- and 2D-NMR, CD and MS spectroscopic analyses. PMID- 26287130 TI - Mimosine Dipeptide Enantiomsers: Improved Inhibitors against Melanogenesis and Cyclooxygenase. AB - Melanogenesis plays an important role in the protection of skin against UV through production of melanin pigments, but abnormal accumulation of this pigment causes unaesthetic hyperpigmentation. Much effort is being made to develop effective depigmenting agents. Here, we show for the first time that a small library of mimosine dipeptide enantiomers (Mi-L/D-amino acid) inhibit the melanogenesis in B16F10 melanoma cells by down-regulating the cellular tyrosinase with little effect on their growth or viability. Two of them, Mi-D-Trp and Mi-D Val, turned out to be the most potent inhibitors on melanin content and cellular tyrosinase in B16F10 melanoma cells. In addition, most of the mimosine dipeptides were more potent than mimosine for inhibiting cyclooxygenase 1 (COX-1) with IC50 of 18-26 MUM. Among them, Mi-L-Val and Mi-L-Trp inhibited cyclooxygenase 2 (COX 2) more potently than indomethacin, with IC50 values of 22 and 19 MUM, respectively. Taken together, our results suggest the possibility that mimosine dipeptides could be better candidates (than mimosine) for anti-melanogenic (skin hyperpigmentation treatment) and cyclooxygenase (COX) inhibition. PMID- 26287131 TI - Macrophage Activation by Ursolic and Oleanolic Acids during Mycobacterial Infection. AB - Oleanolic (OA) and ursolic acids (UA) are triterpenes that are abundant in vegetables, fruits and medicinal plants. They have been described as active moieties in medicinal plants used for the treatment of tuberculosis. In this study, we analyzed the effects of these triterpenes on macrophages infected in vitro with Mycobacterium tuberculosis (MTB). We evaluated production of nitric oxide (NO), reactive oxygen species (ROS), and cytokines (TNF-alpha and TGF-beta) as well as expression of cell membrane receptors (TGR5 and CD36) in MTB-infected macrophages following treatment with OA and UA. Triterpenes caused reduced MTB growth in macrophages, stimulated production of NO and ROS in the early phase, stimulated TNF-alpha, suppressed TGF-beta and caused over-expression of CD36 and TGR5 receptors. Thus, our data suggest immunomodulatory properties of OA and UA on MTB infected macrophages. In conclusion, antimycobacterial effects induced by these triterpenes may be attributable to the conversion of macrophages from stage M2 (alternatively activated) to M1 (classically activated). PMID- 26287132 TI - Synthesis, Characterization, and Anti-Cancer Activity of Some New N'-(2 Oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazones Derivatives. AB - Eight novel N'-(2-oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazone derivatives 4a-h were synthesized and fully characterized by IR, NMR ((1)H-NMR and (13)C-NMR), elemental analysis, and X-ray crystallography. The cyto-toxicity and in vitro anti-cancer evaluation of the prepared compounds have been assessed against two different human tumour cell lines including human liver (HepG2) and leukaemia (Jurkat), as well as in normal cell lines derived from human embryonic kidney (HEK293) using MTT assay. The compounds 3e, 3f, 4a, 4c, and 4e revealed promising anti-cancer activities in tested human tumour cells lines (IC50 values between 3 and 7 MUM) as compared to the known anti-cancer drug 5-Fluorouracil (IC50 32-50 MUM). Among the tested compounds, 4a showed specificity against leukaemia (Jurkat) cells, with an IC50 value of 3.14 MUM, but this compound was inactive in liver cancer and normal cell lines. PMID- 26287133 TI - Synthesis and Photophysical Properties of Polycarbo-Substituted Quinazolines Derived from the 2-Aryl-4-chloro-6-iodoquinazolines. AB - The reactivity of the 2-aryl-4-chloro-6-iodoquinazolines towards palladium catalyzed sequential (Sonogashira/Suzuki-Miyaura) and one-pot two-step cross coupling (bis-Sonogashira, and successive Sonogashira/Stille) reactions to afford novel unsymmetrical polycarbo-substituted quinazolines has been evaluated. In contrast to the chloro-bromo substituted quinazolines in which selectivity has been previously found to generally favor substitution at the more activated C(4) Cl bond over the weaker Csp(2)-Br bond, substitution in the case of the chloro iodo derivatives favors cross-coupling through the intrinsically more reactive Csp(2)-I bond. The electronic absorption and emission properties of the prepared 2,3-diaryl-6-(phenylethynyl)quinazolines were studied in solvents of different polarity (dichloromethane, toluene, DMF, methanol) and CH2Cl2-TFA mixture using UV-Vis and emission spectroscopic techniques complemented with density functional theory method to establish the effect of substituents on intramolecular charge transfer properties. PMID- 26287134 TI - Influence of Solid Drug Delivery System Formulation on Poorly Water-Soluble Drug Dissolution and Permeability. AB - The majority of drugs have a low dissolution rate, which is a limiting step for their absorption. In this manuscript, solid dispersions (SD), solid self microemulsifying drug delivery systems (S-SMEDDS) and solid self-nanoemulsifying drug delivery systems (S-SNEDDS) were evaluated as potential formulation strategies to increase the dissolution rate of carbamazepine. Influence of increased dissolution rate on permeability of carbamazepine was evaluated using PAMPA test. In S-SMEDDS and S-SNEDDS formulations, the ratio of liquid SMEDDS/SNEDDS and solid carrier (Neusilin((r)) UFL2) was varied, and carbamazepine content was constant. In SD formulations, the ratio of carbamazepine and Neusilin((r)) UFL2, was varied. Formulations that showed the best dissolution rate of carbamazepine (SD_1:6, SMEDDS_1:1, SNEDDS_1:6) were mutually compared, characterization of these formulations was performed by DSC, PXRD and FT-IR analyses, and a PAMPA test was done. All formulations have shown a significant increase in dissolution rate compared to pure carbamazepine and immediate-release carbamazepine tablets. Formulation S-SMEDDS_1:1 showed the fastest release rate and permeability of carbamazepine. DSC, PXRD and FT-IR analyses confirmed that in S-SMEDDS and S-SNEDDS carbamazepine remained in polymorph form III, and that it was converted to an amorphous state in SD formulations. All formulations showed increased permeability of carbamazepine, compared to pure carbamazepine. PMID- 26287135 TI - Synthesis and Consecutive Reactions of alpha-Azido Ketones: A Review. AB - This review paper covers the major synthetic approaches attempted towards the synthesis of alpha-azido ketones, as well as the synthetic applications/consecutive reactions of alpha-azido ketones. PMID- 26287136 TI - Synthesis of Photoswitchable Magnetic Au-Fullerosome Hybrid Nanomaterials for Permittivity Enhancement Applications. AB - We designed and synthesized several nanomaterials 3 of three-layered core-shell (gamma-FeOx@AuNP)@[C60(>DPAF-C9) 1 or 2]n nanoparticles (NPs). These NPs having e(-)-polarizable fullerosome structures located at the outer layer were fabricated from highly magnetic core-shell gamma-FeOx@AuNPs. Fullerosomic polarization of 3 was found to be capable of causing a large amplification of material permittivity that is also associated with the photoswitching effect in the frequency range of 0.5-4.0 GHz. Multilayered synthetic construction allows Forster resonance energy transfer (FRET) of photoinduced accumulative surface plasmon resonance (SPR) energy in the gold layer to the partially bilayered C60(>DPAF-C9) 1 or 2-derived fullerosome membrane shell layer in a near-field of direct contact without producing radiation heat, which is commonly associated with SPR. PMID- 26287137 TI - Synthesis, Structural Studies and Molecular Modelling of a Novel Imidazoline Derivative with Antifungal Activity. AB - Six novel imidazoline derivatives were synthesized and tested in antifungal assays. One of the compounds, N-cyclohexyl-2-imino-3-(4-nitrophenyl)imidazolidine 1-carboxamide showed moderate activity against several clinical strains of Candida albicans. Its structure was solved by X-ray crystallography and its mode of action was deduced using molecular modelling. It was found to be similar to that of fluconazole. The potential for further optimization including SAR of the compound is briefly discussed. PMID- 26287138 TI - Rapid Estimation of Tocopherol Content in Linseed and Sunflower Oils-Reactivity and Assay. AB - The reactivity of tocopherols with 2,2-diphenyl-1-picrylhydrazyl (DPPH) was studied in model systems in order to establish a method for quantifying vitamin E in plant oils. The method was optimized with respect to solvent composition of the assay medium, which has a large influence on the course of reaction of tocopherols with DPPH. The rate of reaction of alpha-tocopherol with DPPH is higher than that of gamma-tocopherol in both protic and aprotic solvents. In ethyl acetate, routinely applied for the analysis of antioxidant potential (AOP) of plant oils, reactions of tocopherols with DPPH are slower and concentration of tocopherols in the assay has a large influence on their molar reactivity. In 2 propanol, however, two electrons are exchanged for both alpha- and gamma tocopherols, independent of their concentration. 2-propanol is not toxic and is fully compatible with polypropylene labware. The chromatographically determined content of tocopherols and their molar reactivity in the DPPH assay reveal that only tocopherols contribute to the AOP of sunflower oil, whereas the contribution of tocopherols to the AOP of linseed oil is 75%. The DPPH assay in 2-propanol can be applied for rapid and cheap estimation of vitamin E content in plant oils where tocopherols are major antioxidants. PMID- 26287139 TI - Novel Coumarin-Containing Aminophosphonatesas Antitumor Agent: Synthesis, Cytotoxicity, DNA-Binding and Apoptosis Evaluation. AB - A series of novel coumarin-containing alpha-aminophosphonates were synthesized and evaluated for their antitumor activities against Human colorectal (HCT-116), human nasopharyngeal carcinoma (human KB) and human lung adenocarcinoma (MGC-803) cell lines in vitro. Compared with 7-hydroxy-4-methylcoumarin (4-MU), most of the derivatives showed an improved antitumor activity. Compound 8j (diethyl 1-(3-(4 methyl-2-oxo-2H-chromen-7-yloxy) propanamido)-1-phenylethyl-Phosphonate), with IC50 value of 8.68 MUM against HCT-116 cell lines, was about 12 fold than that of unsubstituted parent compound. The mechanism investigation proved that 8c, 8d, 8f and 8j were achieved through the induction of cell apoptosis by G1 cell-cycle arrest. In addition, the further mechanisms of compound 8j-induced apoptosis in HCT-116 cells demonstrated that compound 8j induced the activations of caspase-9 and caspase-3 for causing cell apoptosis, and altered anti- and pro-apoptotic proteins. DNA-binding experiments suggested that some derivatives bind to DNA through intercalation. The results seem to imply the presence of an important synergistic effect between coumarin and aminophosphonate, which could contribute to the strong chelating properties of aminophosphonate moiety. PMID- 26287140 TI - Bioassay-Guided Fractionation of a Leaf Extract from Combretum mucronatum with Anthelmintic Activity: Oligomeric Procyanidins as the Active Principle. AB - Combretum mucronatum Schumach. & Thonn. is a medicinal plant widely used in West African traditional medicine for wound healing and the treatment of helminth infections. The present study aimed at a phytochemical characterization of a hydroalcoholic leaf extract of this plant and the identification of the anthelmintic compounds by bioassay-guided fractionation. An EtOH-H2O (1:1) extract from defatted leaves was partitioned between EtOAc and H2O. Further fractionation was performed by fast centrifugal partition chromatography, RP18 MPLC and HPLC. Epicatechin (1), oligomeric proanthocyanidins (OPC) 2 to 10 (mainly procyanidins) and flavonoids 11 to 13 were identified as main components of the extract. The hydroalcoholic extract, fractions and purified compounds were tested in vitro for their anthelmintic activity using the model nematode Caenorhabditis elegans. The bioassay-guided fractionation led to the identification of OPCs as the active compounds with a dose-dependent anthelmintic activity ranging from 1 to 1000 MUM. Using OPC-clusters with a defined degree of polymerization (DP) revealed that a DP >= 3 is necessary for an anthelmintic activity, whereas a DP > 4 does not lead to a further increased inhibitory effect against the helminths. In summary, the findings rationalize the traditional use of C. mucronatum and provide further insight into the anthelmintic activity of condensed tannins. PMID- 26287141 TI - Non-Covalent Derivatives: Cocrystals and Eutectics. AB - Non-covalent derivatives (NCDs) are formed by incorporating one (or more) coformer molecule(s) into the matrix of a parent molecule via non-covalent forces. These forces can include ionic forces, Van der Waals forces, hydrogen bonding, lipophilic-lipophilic interactions and pi-pi interactions. NCDs, in both cocrystal and eutectic forms, possess properties that are unique to their supramolecular matrix. These properties include critical product performance factors such as solubility, stability and bioavailability. NCDs have been used to tailor materials for a variety of applications and have the potential to be used in an even broader range of materials and processes. NCDs can be prepared using little or no solvent and none of the reagents typical to synthetic modifications. Thus, NCDs represent a powerfully versatile, environmentally-friendly and cost effective opportunity. PMID- 26287142 TI - Structural Stabilities and Transformation Mechanism of Rhynchophylline and Isorhynchophylline by Ultra Performance Liquid Chromatography/Time-of-Flight Mass Spectrometry (UPLC/Q-TOF-MS). AB - To reveal the structural stabilities and transformation mechanism of rhynchophylline (RIN) and isorhynchophylline (IRN), HPLC and UPLC-Q-TOF-MS method were developed for the qualitative and quantitative analysis of the conversion rate. The method was validated for linearity, inter- and intra-day precisions, repeatability and stability. All the quantitative determination method validation results were satisfactory. Under the optimized chromatographic conditions, the effect of various heat temperatures, retention time, and solvent polarities on conversion rate and equilibrium were systematically investigated for the first time. Besides, a model relating the retention yield value and time-temperature was built to predict the t0.5 and Ea of the conversion rate by the Arrhenius equation. The experimental results proved to be in good accordance with the predicted values. Furthermore, UPLC-Q-TOF-MS analysis was performed to verify the transformation mechanism and provide valuable information for stability analysis of the conversion products. PMID- 26287143 TI - Development of a Single Vial Kit Solution for Radiolabeling of 68Ga-DKFZ-PSMA-11 and Its Performance in Prostate Cancer Patients. AB - Prostate-specific membrane antigen (PSMA), a type II glycoprotein, is highly expressed in almost all prostate cancers. By playing such a universal role in the disease, PSMA provides a target for diagnostic imaging of prostate cancer using positron emission tomography/computed tomography (PET/CT). The PSMA-targeting ligand Glu-NH-CO-NH-Lys-(Ahx)-HBED-CC (DKFZ-PSMA-11) has superior imaging properties and allows for highly-specific complexation of the generator-based radioisotope Gallium-68 ((68)Ga). However, only module-based radiolabeling procedures are currently available. This study intended to develop a single vial kit solution to radiolabel buffered DKFZ-PSMA-11 with (68)Ga. A (68)Ge/(68)Ga generator was utilized to yield (68)GaCl3 and major aspects of the kit development were assessed, such as radiolabeling performance, quality assurance, and stability. The final product was injected into patients with prostate cancer for PET/CT imaging and the kit performance was evaluated on the basis of the expected biodistribution, lesion detection, and dose optimization. Kits containing 5 nmol DKFZ-PSMA-11 showed rapid, quantitative (68)Ga-complexation and all quality measurements met the release criteria for human application. The increased precursor content did not compromise the ability of (68)Ga-DKFZ-PSMA-11 PET/CT to detect primary prostate cancer and its advanced lymphatic- and metastatic lesions. The (68)Ga-DKFZ-PSMA-11 kit is a robust, ready-to-use diagnostic agent in prostate cancer with high diagnostic performance. PMID- 26287144 TI - Diterpenoids from Saliva plebeia R. Br. and Their Antioxidant and Anti Inflammatory Activities. AB - A new skeleton of diterpenoid, 1,2,3,4,4alpha,9,10,10alpha-octahydro-(4alpha hydroxyymethyl) -1,1-dimethyl-9-(1-methylethyl)-(2S,3S,4alphaR,9R,10alphaS) 2,3,5,7-phenanthrenetertrol, named plebeianiol A (1), along with four known diterpenoids (2-5), were isolated from Salvia plebeia R. Br. Their structures were determined on the basis of spectral analysis. In the bioactivity tests, compounds 1, 2 and 5 showed 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities with IC50 values of 20.0-29.6 uM. In addition, these three compounds had significant inhibitory effects on reactive oxygen species (ROS) production in lipopolysaccharide (LPS)-induced macrophages. Compounds 1-3 inhibited nitric oxide (NO) production in LPS-induced macrophages with IC50 values of 18.0-23.6 uM. These results showed that compounds 1, 2 had significant antioxidant and anti-inflammatory activities and might provide basis for the treatment of diseases associated with oxidative lesions and inflammation. PMID- 26287145 TI - Recombinant Production of Snakin-2 (an Antimicrobial Peptide from Tomato) in E. coli and Analysis of Its Bioactivity. AB - Antimicrobial peptides (AMPs) represent a diverse group of biologically active molecules that are part of the innate immune systems of a variety of organisms. Their primary function consists of protecting the host organism against invading microorganisms, including pathogens. AMPs show a broad spectrum of secondary structures, which are essential for antimicrobial activity. In this study, we produced snakin-2 (SN2), a 66-amino-acid-(aa)-long AMP from Solanum lycopersicum as a recombinant protein in E. coli. This AMP belongs to the GASA/GAST protein family and possesses a highly conserved 60-aa-long domain with six disulfide bonds in the C-terminus of the peptide. Because of the toxicity of SN2 against its producing E. coli strain, the AMP was attached to an N-terminal fusion protein (thioredoxin A), which was removed after affinity chromatography purification. The total yield of recombinant SN2 was approximately 1 mg/L. The membrane-active SN2 showed a bactericidal and fungicidal bioactivity, which can be explained by perforation of biomembranes of bacteria and fungi. PMID- 26287146 TI - Synthesis of C3/C1-Substituted Tetrahydroisoquinolines. AB - A broad biological screening of the natural alkaloid N-methylisosalsoline (2) extracted from Hammada scoparia leaves against a panel of human and parasitic proteases revealed an interesting activity profile of 2 towards human 20S proteasome. This outcome suggests that the 1,2,3,4-tetrahydroisoquinoline skeleton may be exploited as a template for the development of novel anticancer agents. In this article, we report the synthesis and chemical characterization of a new series of isosalsoline-type alkaloids (10-11) with variations at N2 and C3 positions with respect to the natural Compound 2, obtained by a synthetic strategy that involves the Bischler-Napieralski cyclization. The substrate for the condensation to the tetrahydroisoquinoline system, i.e., a functionalized beta-arylethyl amine, was obtained through an original double reduction of nitroalkene. The synthetic strategy can be directed to the construction of highly substituted and functionalized 1,2,3,4-tetrahydroisoquinolines. PMID- 26287147 TI - A Combined Molecular Docking/Dynamics Approach to Probe the Binding Mode of Cancer Drugs with Cytochrome P450 3A4. AB - Cytarabine, daunorubicin, doxorubicin and vincristine are clinically used for combinatorial therapies of cancers in different combinations. However, the knowledge about the interaction of these drugs with the metabolizing enzyme cytochrome P450 is limited. Therefore, we utilized computational methods to predict and assess the drug-binding modes. In this study, we performed docking, MD simulations and free energy landscape analysis to understand the drug-enzyme interactions, protein domain motions and the most populated free energy minimum conformations of the docked protein-drug complexes, respectively. The outcome of docking and MD simulations predicted the productive, as well as the non productive binding modes of the selected drugs. Based on these interaction studies, we observed that S119, R212 and R372 are the major drug-binding residues in CYP3A4. The molecular mechanics Poisson-Boltzmann surface area analysis revealed the dominance of hydrophobic forces in the CYP3A4-drug association. Further analyses predicted the residues that may contain favorable drug-specific interactions. The probable binding modes of the cancer drugs from this study may extend the knowledge of the protein-drug interaction and pave the way to design analogs with reduced toxicity. In addition, they also provide valuable insights into the metabolism of the cancer drugs. PMID- 26287148 TI - Eco-Friendly Synthesis of a New Class of Pyridinium-Based Ionic Liquids with Attractive Antimicrobial Activity. AB - The present study reports a green synthesis of a new family of ionic liquids (ILs) based on functionalized 4-dimethylaminopyridinium derivatives. The structures of 23 newly synthesized ILs (2-24) were confirmed by FT-IR, (1)H-, (13)C-, (11)B-, (19)F-, and (31)P-NMR spectroscopy and mass spectrometry. The antimicrobial activity of all novel ILs was tested against a panel of bacteria and fungi. The results prove that all tested ILs are effective antibacterial and antifungal agents, especially 4-(dimethylamino)-1-(4-phenoxybutyl) pyridinium derivatives 5 and 19. PMID- 26287149 TI - Oral Intake of Carboxymethyl-Glucan (CM-G) from Yeast (Saccharomyces uvarum) Reduces Malondialdehyde Levels in Healthy Men. AB - Carboxymethyl-glucan (CM-G) is a water-soluble derivative of beta(1 -> 3)(1 -> 6) glucan, a well-known immunostimulant and antioxidant compound. In this experimental, randomized and placebo-controlled study, the effects of oral CM-G intake over a 60-day period on the peripheral blood, cholesterol, glycemic index and malondialdehyde (MDA) levels of healthy men was assessed. The CM-G was obtained from spent brewer's yeast (S. uvarum) with DS 0.8 and molecular weight of 2.2 * 10(5) Da. Following CM-G administration, no changes were observed in red and white blood cell, hematocrit, hemoglobin and platelet counts, or in cholesterol and glycemic indices. After 30 days of CM-G administration, the MDA levels decreased significantly (p <= 0.05) in men receiving CM-G. The results showed for the first time that CM-G may act as an adjuvant in preventing oxidative damage in healthy humans. PMID- 26287150 TI - Inhibitory Activity of Yokukansankachimpihange against Nerve Growth Factor Induced Neurite Growth in Cultured Rat Dorsal Root Ganglion Neurons. AB - Chronic pruritus is a major and distressing symptom of many cutaneous diseases, however, the treatment remains a challenge in the clinic. The traditional Chinese Japanese medicine (Kampo medicine) is a conservative and increasingly popular approach to treat chronic pruritus for both patients and medical providers. Yokukansankachimpihange (YKH), a Kampo formula has been demonstrated to be effective in the treatment of itching of atopic dermatitis in Japan although its pharmacological mechanism is unknown clearly. In an attempt to clarify its pharmacological actions, in this study, we focused on the inhibitory activity of YKH against neurite growth induced with nerve growth factor (NGF) in cultured rat dorsal root ganglion (DRG) neurons because epidermal hyperinnervation is deeply related to itch sensitization. YKH showed approximately 200-fold inhibitory activity against NGF-induced neurite growth than that of neurotropin (positive control), a drug used clinically for treatment of chronic pruritus. Moreover, it also found that Uncaria hook, Bupleurum root and their chemical constituents rhynchophylline, hirsutine, and saikosaponin a, d showed inhibitory activities against NGF-induced neurite growth, suggesting they should mainly contribute to the inhibitory activity of YKH. Further study on the effects of YKH against epidermal nerve density in "itch-scratch" animal models is under investigation. PMID- 26287151 TI - Fast Identification of Radical Scavengers from Securigera varia by Combining 13C NMR-Based Dereplication to Bioactivity-Guided Fractionation. AB - Securigera varia (Fabaceae) is a common herbaceous perennial plant widely growing in Europe and Asia and purposely established for erosion control, roadside planting, and soil rehabilitation. The aim of this study was to determine the radical scavenging activity of a crude methanol extract of S. varia aerial parts by using the free radical DPPH (1,1-diphenyl-2-picrylhydrazyl) and to rapidly identify the compounds involved in this activity. The crude extract was initially separated in five fractions on Diaion HP20 resin and the most active part was fractionated by Centrifugal Partition Extraction (CPE). Known compounds were directly identified by a (13)C-NMR-based dereplication method. Semi-preparative high performance liquid chromatography purification experiments were further performed to identify unknown or minor active compounds. As a result, one new (13) and twelve known flavonoid glycosides together with three nitropropanoylglucopyranoses were isolated, including astragalin (1), kaempferol 3-O-(6-O-acetyl)-beta-D-glucopyranoside (2), kaempferol-3,4'-di-O-beta-D glucopyranoside (3), trifolin (4), isoquercitrin (5), hyperoside (6), isovitexin (7), isoorientin (8), isovitexin 4'-O-beta-D-glucopyranoside (9), apigenin 7-O beta-D-glucuronopyranoside (10), luteolin 7-O-beta-D-glucuronopyranoside (11), apigenin 7-O-alpha-L-rhamnopyranosyl-(1->2)-beta-D-glucuronopyranoside (12), apigenin 7-O-beta-D-glucopyranosyl-(1 -> 2)-beta-D-glucuronopyranoside (13), 6-O (3-nitropropanoyl)-beta-D-glucopyranoside (14), coronillin (16) and coronarian (15). 120 mg of the most active compound isoorientin against the free radical DPPH was recovered by CPE with an HPLC purity of 99%. PMID- 26287152 TI - Effect of Brewing Duration on the Antioxidant and Hepatoprotective Abilities of Tea Phenolic and Alkaloid Compounds in a t-BHP Oxidative Stress-Induced Rat Hepatocyte Model. AB - Tea is an interesting source of antioxidants capable of counteracting the oxidative stress implicated in liver diseases. We investigated the impact of antioxidant molecules provided by a mixture of teas' leaves (green, oolong, pu erh) after different infusion durations in the prevention of oxidative stress in isolated rat hepatocytes, by comparison with pure epigallocatechin-3-gallate (EGCG), the main representative of tea catechins. Dried aqueous tea extracts (ATE) obtained after 5, 15 and 30 min infusion time were characterized for total polyphenols (gallic acid equivalent), catechins, gallic acid and caffeine (HPLC DAD/ESI-MS) contents, and for scavenging ability against 2,2-diphenyl-1 picrylhydrazyl free radical. Hepatoprotection was evaluated through hepatocyte viability tests using tert-butyl hydroperoxide as a stress inducer, (3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, neutral red uptake, real time cellular impedance) and mitochondrial function tests. We showed that a 5-min incubation time is sufficient for an optimal bioaccessibility of tea compounds with the highest antioxidative ability, which decreases for longer durations. A 4 h pretreatment of cells with ATE significantly prevented cell death by regulating reactive oxygen species production and maintaining mitochondrial integrity. Pure EGCG, at doses similar in ATE (5-12 uM), was inefficient, suggesting a plausible synergy of several water-soluble tea compounds to explain the ATE beneficial effects. PMID- 26287153 TI - Ethnomedicinal, Phytochemical and Pharmacological Profile of Anthriscus sylvestris as an Alternative Source for Anticancer Lignans. AB - Anthriscus sylvestris (L.) Hoffm. is a wild herbaceous plant common in most temperate regions. It has been used traditionally to treat headaches, as a tonic, as antitussive, antipyretic, analgesic and diuretic. The plant contains deoxypodophyllotoxin, which is proven to have antitumor and anti-proliferative effects, anti-platelet aggregation, antiviral, anti-inflammatory and insecticidal activity. Deoxypodophyllotoxin is considered to be the plant's most important constituent, because of its pharmacological properties and because it can be converted into epipodophyllotoxin, the main raw material for the semisynthesis of the cytostatic agents etoposide and teniposide. This work summarizes for the first time the results related to the botanical description, distribution and habitat, phytochemical and pharmacological properties and emphasizes the aspects for future biotechnological research to establish its utility in the therapeutic arsenal. PMID- 26287154 TI - Copper-Catalyzed Dimerization/Cyclization of Itaconates. AB - A copper-catalyzed domino reaction between itaconate esters and diethyl zinc (or silane) is developed, affording itaconate dimerization products, multi-ester substituted cyclopentanones, in moderate to high yields. PMID- 26287155 TI - Inhibition of Cytosolic Phospholipase A2alpha (cPLA2alpha) by Medicinal Plants in Relation to Their Phenolic Content. AB - The cytosolic phospholipase A2alpha(cPLA2alpha) is one of the potential targets for anti-inflammatory drugs, since this enzyme plays a key role in the inflammation processes seen in health disorders, like asthma, allergic reactions, arthritis and neuronal diseases. In this study, cPLA2alpha inhibition by 43 methanol extracts from medicinal plants rich in polyphenols was determined. The eight most active extracts were derived from Ribes nigrum (IC50 of 27.7 MUg/mL), Ononis spinosa (IC50 of 39.4 MUg/mL), Urtica dioica (IC50 of 44.32 MUg/mL), Betula sp. (IC50 of 58.02 MUg/mL), Sanguisorba officinalis (IC50 of 76.25 MUg/mL), Orthosiphon stamineus (IC50 of 78.83 MUg/mL), Petasites hybridus (IC50 of 81.02 MUg/mL) and Tussilago farfara (IC50 of 123.28 MUg/mL). Additionally, the antioxidant activities of these extracts were determined with the 2,2-diphenyl-1 picrylhydrazyl (DPPH) assay and their phenolic content with the Folin-Ciocalteu reagent. Antioxidant activity showed a non-linear, positive correlation to the phenolic content, but no correlation of PLA2 inhibition with phenolic content could be established. This study provides evidence that cPLA2alpha may be a relevant target for anti-inflammatory agents. PMID- 26287156 TI - One-Pot Synthesis of Organic-Sulfur-Zinc Hybrid Materials via Polycondensation of a Zinc Salt and Thiols Generated in Situ from Cyclic Dithiocarbonates. AB - Soluble organic-sulfur-zinc hybrid polymers were prepared via a one-pot reaction consisting of ring-opening addition and subsequent polycondensation. The first reaction is the nucleophilic ring-opening addition of 2-ethylhexylamine to multifunctional cyclic dithiocarbonates giving multiple thiols in situ. The sequential polycondensation of the in situ generated thiols with Zn(OAc)2 gave the target hybrid polymers. This one-pot method enabled the use of a shorter amine than the previous polycondensation of Zn(OAc)2 and purified thiols, which required octadecylamine to obtain a soluble product. The obtained hybrid polymers may be cast as composite films with polystyrene and poly(methyl methacrylate). Owing to the shorter alkyl chain, the calculated nD values of the products (1.60 or 1.61) are higher than that of the previous product bearing octadecyl chains (1.53). PMID- 26287157 TI - Antioxidant, Antimicrobial Effects and Phenolic Profile of Lycium barbarum L. Flowers. AB - L. barbarum L. is a widely-accepted nutraceutical presenting highly advantageous nutritive and antioxidant properties. Its flowers have been previously described as a source of diosgenin, beta-sitosterol and lanosterol that can be further pharmaceutically developed, but no other data regarding their composition is available. The purpose of this work was to investigate the chemical constituents, antioxidant and antimicrobial activities of L. barbarum flowers, as an alternative resource of naturally-occurring antioxidant compounds. The free radical scavenging activity of the ethanolic extract was tested by TEAC, two enzymatic assays with more physiological relevance and EPR spectroscopy. The presence of several phenolic compounds, such as chlorogenic, p-coumaric and ferulic acids, but also isoquercitrin, rutin and quercitrin, was assessed by an HPLC/MS method. The antioxidant assays revealed that the extract exhibited a moderate antioxidant potential. The antimicrobial activity was mild against Gram positive bacteria and lacking against Escherichia coli. These findings complete the scarce existing data and offer new perspectives for further pharmaceutical valorization of L. barbarum flowers. PMID- 26287160 TI - The Histone Deacetylase Inhibitor BML-210 Influences Gene and Protein Expression in Human Promyelocytic Leukemia NB4 Cells via Epigenetic Reprogramming. AB - Today, cancer is understood as an epigenetic as well as genetic disease. The main epigenetic hallmarks of the cancer cell are DNA methylation and histone modifications. Proteins such as histone deacetylases (HDACs) that cause modifications of histones and other proteins can be targets for novel anticancer agents. Recently, interest in compounds that can inhibit HDACs increased, and now there are many HDACs inhibitors (HDACIs) available with different chemical structures, biological and biochemical properties; hopefully some of them will succeed, probably in combination with other agents, in cancer therapies. In our study we focused on the novel HDACI-BML-210. We found that BML-210 (N-phenyl-N' (2-Aminophenyl)hexamethylenediamide) inhibits the growth of NB4 cells in dose- and time-dependent manner. In this study we also examined how expression and activity of HDACs are affected after leukemia cell treatment with BML-210. Using a mass spectrometry method we identified proteins that changed expression after treatment with BML-210. We prepared RT-PCR analysis of these genes and the results correlated with proteomic data. Based on these and other findings from our group, we suggest that HDACIs, like BML-210, can be promising anticancer agents in promyelocytic leukemia treatment. PMID- 26287161 TI - Kynurenines and Multiple Sclerosis: The Dialogue between the Immune System and the Central Nervous System. AB - Multiple sclerosis is an inflammatory disease of the central nervous system, in which axonal transection takes place in parallel with acute inflammation to various, individual extents. The importance of the kynurenine pathway in the physiological functions and pathological processes of the nervous system has been extensively investigated, but it has additionally been implicated as having a regulatory function in the immune system. Alterations in the kynurenine pathway have been described in both preclinical and clinical investigations of multiple sclerosis. These observations led to the identification of potential therapeutic targets in multiple sclerosis, such as synthetic tryptophan analogs, endogenous tryptophan metabolites (e.g., cinnabarinic acid), structural analogs (laquinimod, teriflunomid, leflunomid and tranilast), indoleamine-2,3-dioxygenase inhibitors (1MT and berberine) and kynurenine-3-monooxygenase inhibitors (nicotinylalanine and Ro 61-8048). The kynurenine pathway is a promising novel target via which to influence the immune system and to achieve neuroprotection, and further research is therefore needed with the aim of developing novel drugs for the treatment of multiple sclerosis and other autoimmune diseases. PMID- 26287162 TI - Microwave-Induced Chemotoxicity of Polydopamine-Coated Magnetic Nanocubes. AB - Polydopamine-coated FeCo nanocubes (PDFCs) were successfully synthesized and tested under microwave irradiation of 2.45 GHz frequency and 0.86 W/cm(2) power. These particles were found to be non-toxic in the absence of irradiation, but gained significant toxicity upon irradiation. Interestingly, no increase in relative heating rate was observed when the PDFCs were irradiated in solution, eliminating nanoparticle (NP)-induced thermal ablation as the source of toxicity. Based on these studies, we propose that microwave-induced redox processes generate the observed toxicity. PMID- 26287163 TI - Physiological and Molecular Aspects of Tolerance to Environmental Constraints in Grain and Forage Legumes. AB - Despite the agronomical and environmental advantages of the cultivation of legumes, their production is limited by various environmental constraints such as water or nutrient limitation, frost or heat stress and soil salinity, which may be the result of pedoclimatic conditions, intensive use of agricultural lands, decline in soil fertility and environmental degradation. The development of more sustainable agroecosystems that are resilient to environmental constraints will therefore require better understanding of the key mechanisms underlying plant tolerance to abiotic constraints. This review provides highlights of legume tolerance to abiotic constraints with a focus on soil nutrient deficiencies, drought, and salinity. More specifically, recent advances in the physiological and molecular levels of the adaptation of grain and forage legumes to abiotic constraints are discussed. Such adaptation involves complex multigene controlled traits which also involve multiple sub-traits that are likely regulated under the control of a number of candidate genes. This multi-genetic control of tolerance traits might also be multifunctional, with extended action in response to a number of abiotic constraints. Thus, concrete efforts are required to breed for multifunctional candidate genes in order to boost plant stability under various abiotic constraints. PMID- 26287164 TI - Angiogenesis-Related Biomarkers (sFlt-1/PLGF) in the Prediction and Diagnosis of Placental Dysfunction: An Approach for Clinical Integration. AB - Placental dysfunction is involved in a group of obstetrical conditions including preeclampsia, intrauterine growth restriction, and placental abruption. Their timely and accurate recognition is often a challenge since diagnostic criteria are still based on nonspecific signs and symptoms. The discovering of the role of angiogenic-related factors (sFlt-1/PlGF) in the underlying pathophysiology of placental dysfunction, taking into account that angiogenesis-related biomarkers are not specific to any particular placental insufficiency-related disease, has marked an important step for improving their early diagnosis and prognosis assessment. However, sFlt-1/PlGF has not been yet established as a part of most guidelines. We will review the current evidence on the clinical utility of sFlt 1/PlGF and propose a new protocol for its clinical integration. PMID- 26287165 TI - Human Dermal Stem/Progenitor Cell-Derived Conditioned Medium Improves Senescent Human Dermal Fibroblasts. AB - Adult skin stem cells are recognized as potential therapeutics to rejuvenate aged skin. We previously demonstrated that human dermal stem/progenitor cells (hDSPCs) with multipotent capacity could be enriched from human dermal fibroblasts using collagen type IV. However, the effects of hDSPCs on cellular senescence remain to be elucidated. In the present study, we investigated whether conditioned medium (CM) collected from hDSPC cultures (hDSPC-CM) exhibits beneficial effects on senescent fibroblasts. We found that hDSPC-CM promoted proliferation and decreased the expression level of senescence-associated beta-galactosidase in senescent fibroblasts. In addition, p53 phosphorylation and p21 expression were significantly reduced in senescent fibroblasts treated with hDSPC-CM. hDSPC-CM restored the expression levels of collagen type I, collagen type III, and tissue inhibitor of metalloproteinase, and antagonized the increase of matrix metalloproteinase 1 expression. Finally, we demonstrated that hDSPC-CM significantly reduced reactive oxygen species levels by specifically up regulating the expression level of superoxide dismutase 2. Taken together, these data suggest that hDSPC-CM can be applied as a potential therapeutic agent for improving human aged skin. PMID- 26287166 TI - Disorder Prediction Methods, Their Applicability to Different Protein Targets and Their Usefulness for Guiding Experimental Studies. AB - The role and function of a given protein is dependent on its structure. In recent years, however, numerous studies have highlighted the importance of unstructured, or disordered regions in governing a protein's function. Disordered proteins have been found to play important roles in pivotal cellular functions, such as DNA binding and signalling cascades. Studying proteins with extended disordered regions is often problematic as they can be challenging to express, purify and crystallise. This means that interpretable experimental data on protein disorder is hard to generate. As a result, predictive computational tools have been developed with the aim of predicting the level and location of disorder within a protein. Currently, over 60 prediction servers exist, utilizing different methods for classifying disorder and different training sets. Here we review several good performing, publicly available prediction methods, comparing their application and discussing how disorder prediction servers can be used to aid the experimental solution of protein structure. The use of disorder prediction methods allows us to adopt a more targeted approach to experimental studies by accurately identifying the boundaries of ordered protein domains so that they may be investigated separately, thereby increasing the likelihood of their successful experimental solution. PMID- 26287168 TI - Fumaric Acid Esters Do Not Reduce Inflammatory NF-kappaB/p65 Nuclear Translocation, ICAM-1 Expression and T-Cell Adhesiveness of Human Brain Microvascular Endothelial Cells. AB - Dimethyl fumarate (DMF) is approved for disease-modifying treatment of patients with relapsing-remitting multiple sclerosis. Animal experiments suggested that part of its therapeutic effect is due to a reduction of T-cell infiltration of the central nervous system (CNS) by uncertain mechanisms. Here we evaluated whether DMF and its primary metabolite monomethyl fumarate (MMF) modulate pro inflammatory intracellular signaling and T-cell adhesiveness of nonimmortalized single donor human brain microvascular endothelial cells at low passages. Neither DMF nor MMF at concentrations of 10 or 50 uM blocked the IL-1beta-induced nuclear translocation of NF-kappaB/p65, whereas the higher concentration of DMF inhibited the nuclear entry of p65 in human umbilical vein endothelium cultured in parallel. DMF and MMF also did not alter the IL-1beta-stimulated activation of p38 MAPK in brain endothelium. Furthermore, neither DMF nor MMF reduced the basal or IL-1beta-inducible expression of ICAM-1. In accordance, both fumaric acid esters did not reduce the adhesion of activated Jurkat T cells to brain endothelium under basal or inflammatory conditions. Therefore, brain endothelial cells probably do not directly mediate a potential blocking effect of fumaric acid esters on the inflammatory infiltration of the CNS by T cells. PMID- 26287167 TI - Current Understanding of the Interplay between Phytohormones and Photosynthesis under Environmental Stress. AB - Abiotic stress accounts for huge crop losses every year across the globe. In plants, the photosynthetic machinery gets severely damaged at various levels due to adverse environmental conditions. Moreover, the reactive oxygen species (ROS) generated as a result of stress further promote the photosynthetic damage by inhibiting the repair system of photosystem II. Earlier studies have suggested that phytohormones are not only required for plant growth and development, but they also play a pivotal role in regulating plants' responses to different abiotic stress conditions. Although, phytohormones have been studied in great detail in the past, their influence on the photosynthetic machinery under abiotic stress has not been studied. One of the major factors that limits researchers from elucidating the precise roles of phytohormones is the highly complex nature of hormonal crosstalk in plants. Another factor that needs to be elucidated is the method used for assessing photosynthetic damage in plants that are subjected to abiotic stress. Here, we review the current understanding on the role of phytohormones in the photosynthetic machinery under various abiotic stress conditions and discuss the potential areas for further research. PMID- 26287169 TI - Lead Poisoning Disturbs Oligodendrocytes Differentiation Involved in Decreased Expression of NCX3 Inducing Intracellular Calcium Overload. AB - Lead (Pb) poisoning has always been a serious health concern, as it permanently damages the central nervous system. Chronic Pb accumulation in the human body disturbs oligodendrocytes (OLs) differentiation, resulting in dysmyelination, but the molecular mechanism remains unknown. In this study, Pb at 1 MUM inhibits OLs precursor cells (OPCs) differentiation via decreasing the expression of Olig 2, CNPase proteins in vitro. Moreover, Pb treatment inhibits the sodium/calcium exchanger 3 (NCX3) mRNA expression, one of the major means of calcium (Ca(2+)) extrusion at the plasma membrane during OPCs differentiation. Also addition of KB R7943, NCX3 inhibitor, to simulate Pb toxicity, resulted in decreased myelin basic protein (MBP) expression and cell branching. Ca(2+) response trace with Pb and KB-R7943 treatment did not drop down in the same recovery time as the control, which elevated intracellular Ca(2+) concentration reducing MBP expression. In contrast, over-expression of NCX3 in Pb exposed OPCs displayed significant increase MBP fluorescence signal in positive regions and CNPase expression, which recovered OPCs differentiation to counterbalance Pb toxicity. In conclusion, Pb exposure disturbs OLs differentiation via affecting the function of NCX3 by inducing intracellular calcium overload. PMID- 26287170 TI - Route and Regulation of Zinc, Cadmium, and Iron Transport in Rice Plants (Oryza sativa L.) during Vegetative Growth and Grain Filling: Metal Transporters, Metal Speciation, Grain Cd Reduction and Zn and Fe Biofortification. AB - Zinc (Zn) and iron (Fe) are essential but are sometimes deficient in humans, while cadmium (Cd) is toxic if it accumulates in the liver and kidneys at high levels. All three are contained in the grains of rice, a staple cereal. Zn and Fe concentrations in rice grains harvested under different levels of soil/hydroponic metals are known to change only within a small range, while Cd concentrations show greater changes. To clarify the mechanisms underlying such different metal contents, we synthesized information on the routes of metal transport and accumulation in rice plants by examining metal speciation, metal transporters, and the xylem-to-phloem transport system. At grain-filling, Zn and Cd ascending in xylem sap are transferred to the phloem by the xylem-to-phloem transport system operating at stem nodes. Grain Fe is largely derived from the leaves by remobilization. Zn and Fe concentrations in phloem-sap and grains are regulated within a small range, while Cd concentrations vary depending on xylem supply. Transgenic techniques to increase concentrations of the metal chelators (nicotianamine, 2'-deoxymugineic acid) are useful in increasing grain Zn and Fe concentrations. The elimination of OsNRAMP5 Cd-uptake transporter and the enhancement of root cell vacuolar Cd sequestration reduce uptake and root-to shoot transport, respectively, resulting in a reduction of grain Cd accumulation. PMID- 26287171 TI - Synthesis and in Vitro Antifungal Activity against Botrytis cinerea of Geranylated Phenols and Their Phenyl Acetate Derivatives. AB - The inhibitory effects on the mycelial growth of plant pathogen Botritys cinerea have been evaluated for a series of geranylphenols substituted with one, two and three methoxy groups in the aromatic ring. The results show that the antifungal activity depends on the structure of the geranylphenols, increasing from 40% to 90% by increasing the number of methoxy groups. On the other hand, the acetylation of the -OH group induces a change of activity that depends on the number of methoxy groups. The biological activity of digeranyl derivatives is lower than that exhibited by the respective monogeranyl compound. All tested geranylphenols have been synthesized by direct coupling of geraniol and the respective phenol. The effect of solvent on yields and product distribution is discussed. For monomethoxyphenols the reaction gives better yields when acetonitrile is used as a solvent and AgNO3 is used as a secondary catalyst. However, for di- and trimethoxyphenols the reaction proceeds only in dioxane. PMID- 26287172 TI - Current Status on Stem Cells and Cancers of the Gastric Epithelium. AB - Gastric cancer is still a leading cause of cancer-related mortality worldwide in spite of declining incidence. Gastric cancers are, essentially, adenocarcinomas and one of the strongest risk factors is still infection with Helicobacter pylori. Within the last years, it became clear that gastric self-renewal and carcinogenesis are intimately linked, particularly during chronic inflammatory conditions. Generally, gastric cancer is now regarded as a disease resulting from dysregulated differentiation of stem and progenitor cells, mainly due to an inflammatory environment. However, the situation in the stomach is rather complex, consisting of two types of gastric units which show bidirectional self renewal from an unexpectedly large variety of progenitor/stem cell populations. As in many other tumors, cancer stem cells have also been characterized for gastric cancer. This review focuses on the various gastric epithelial stem cells, how they contribute to self-renewal and which routes are known to gastric adenocarcinomas, including their stem cells. PMID- 26287173 TI - Cdc42-Interacting Protein 4 Represses E-Cadherin Expression by Promoting beta Catenin Translocation to the Nucleus in Murine Renal Tubular Epithelial Cells. AB - Renal fibrosis is an inevitable outcome of end-stage chronic kidney disease. During this process, epithelial cells lose E-cadherin expression. beta-Catenin may act as a mediator by accumulation and translocation to the nucleus. Studies have suggested that CIP4, a Cdc42 effector protein, is associated with beta catenin. However, whether CIP4 contributes to E-cadherin loss in epithelial cells by regulating beta-catenin translocation is unclear. In this study, we investigated the involvement of CIP4 in beta-catenin translocation. Expression of CIP4 was upregulated in renal tissues of 5/6 nephrectomized rats and mainly distributed in renal tubular epithelia. In TGF-beta1-treated NRK-52E cells, upregulation of CIP4 expression was accompanied by reduced expression of E cadherin. CIP4 overexpression promoted the translocation of beta-catenin to the nucleus, which was accompanied by reduced expression of E-cadherin even without TGF-beta1 stimulation. In contrast, CIP4 depletion by using siRNA inhibited the translocation of beta-catenin to the nucleus and reversed the decrease in expression of E-cadherin. The interaction between CIP4 and beta-catenin was detected. We also show that beta-catenin depletion could restore the expression of E-cadherin that was suppressed by CIP4 overexpression. In conclusion, these results suggest that CIP4 overexpression represses E-cadherin expression by promoting beta-catenin translocation to the nucleus. PMID- 26287174 TI - Structure-Based Optimization of Inhibitors of the Aspartic Protease Endothiapepsin. AB - Aspartic proteases are a class of enzymes that play a causative role in numerous diseases such as malaria (plasmepsins), Alzheimer's disease (beta-secretase), fungal infections (secreted aspartic proteases), and hypertension (renin). We have chosen endothiapepsin as a model enzyme of this class of enzymes, for the design, preparation and biochemical evaluation of a new series of inhibitors of endothiapepsin. Here, we have optimized a hit, identified by de novo structure based drug design (SBDD) and DCC, by using structure-based design approaches focusing on the optimization of an amide-pi interaction. Biochemical results are in agreement with SBDD. These results will provide useful insights for future structure-based optimization of inhibitors for the real drug targets as well as insights into molecular recognition. PMID- 26287175 TI - Gene Networks Involved in Hormonal Control of Root Development in Arabidopsis thaliana: A Framework for Studying Its Disturbance by Metal Stress. AB - Plant survival under abiotic stress conditions requires morphological and physiological adaptations. Adverse soil conditions directly affect root development, although the underlying mechanisms remain largely to be discovered. Plant hormones regulate normal root growth and mediate root morphological responses to abiotic stress. Hormone synthesis, signal transduction, perception and cross-talk create a complex network in which metal stress can interfere, resulting in root growth alterations. We focus on Arabidopsis thaliana, for which gene networks in root development have been intensively studied, and supply essential terminology of anatomy and growth of roots. Knowledge of gene networks, mechanisms and interactions related to the role of plant hormones is reviewed. Most knowledge has been generated for auxin, the best-studied hormone with a pronounced primary role in root development. Furthermore, cytokinins, gibberellins, abscisic acid, ethylene, jasmonic acid, strigolactones, brassinosteroids and salicylic acid are discussed. Interactions between hormones that are of potential importance for root growth are described. This creates a framework that can be used for investigating the impact of abiotic stress factors on molecular mechanisms related to plant hormones, with the limited knowledge of the effects of the metals cadmium, copper and zinc on plant hormones and root development included as case example. PMID- 26287176 TI - The Regulatory Role of Signaling Crosstalk in Hypertrophy of MSCs and Human Articular Chondrocytes. AB - Hypertrophic differentiation of chondrocytes is a main barrier in application of mesenchymal stem cells (MSCs) for cartilage repair. In addition, hypertrophy occurs occasionally in osteoarthritis (OA). Here we provide a comprehensive review on recent literature describing signal pathways in the hypertrophy of MSCs derived in vitro differentiated chondrocytes and chondrocytes, with an emphasis on the crosstalk between these pathways. Insight into the exact regulation of hypertrophy by the signaling network is necessary for the efficient application of MSCs for articular cartilage repair and for developing novel strategies for curing OA. We focus on articles describing the role of the main signaling pathways in regulating chondrocyte hypertrophy-like changes. Most studies report hypertrophic differentiation in chondrogenesis of MSCs, in both human OA and experimental OA. Chondrocyte hypertrophy is not under the strict control of a single pathway but appears to be regulated by an intricately regulated network of multiple signaling pathways, such as WNT, Bone morphogenetic protein (BMP)/Transforming growth factor-beta (TGFbeta), Parathyroid hormone-related peptide (PTHrP), Indian hedgehog (IHH), Fibroblast growth factor (FGF), Insulin like growth factor (IGF) and Hypoxia-inducible factor (HIF). This comprehensive review describes how this intricate signaling network influences tissue engineering applications of MSCs in articular cartilage (AC) repair, and improves understanding of the disease stages and cellular responses within an OA articular joint. PMID- 26287178 TI - Tangential Flow Ultrafiltration Allows Purification and Concentration of Lauric Acid-/Albumin-Coated Particles for Improved Magnetic Treatment. AB - Superparamagnetic iron oxide nanoparticles (SPIONs) are frequently used for drug targeting, hyperthermia and other biomedical purposes. Recently, we have reported the synthesis of lauric acid-/albumin-coated iron oxide nanoparticles SEON(LA BSA), which were synthesized using excess albumin. For optimization of magnetic treatment applications, SPION suspensions need to be purified of excess surfactant and concentrated. Conventional methods for the purification and concentration of such ferrofluids often involve high shear stress and low purification rates for macromolecules, like albumin. In this work, removal of albumin by low shear stress tangential ultrafiltration and its influence on SEON(LA-BSA) particles was studied. Hydrodynamic size, surface properties and, consequently, colloidal stability of the nanoparticles remained unchanged by filtration or concentration up to four-fold (v/v). Thereby, the saturation magnetization of the suspension can be increased from 446.5 A/m up to 1667.9 A/m. In vitro analysis revealed that cellular uptake of SEON(LA-BSA) changed only marginally. The specific absorption rate (SAR) was not greatly affected by concentration. In contrast, the maximum temperature Tmax in magnetic hyperthermia is greatly enhanced from 44.4 degrees C up to 64.9 degrees C by the concentration of the particles up to 16.9 mg/mL total iron. Taken together, tangential ultrafiltration is feasible for purifying and concentrating complex hybrid coated SPION suspensions without negatively influencing specific particle characteristics. This enhances their potential for magnetic treatment. PMID- 26287179 TI - Overexpressing Ferredoxins in Chlamydomonas reinhardtii Increase Starch and Oil Yields and Enhance Electric Power Production in a Photo Microbial Fuel Cell. AB - Ferredoxins (FDX) are final electron carrier proteins in the plant photosynthetic pathway, and function as major electron donors in diverse redox-driven metabolic pathways. We previously showed that overexpression of a major constitutively expressed ferredoxin gene PETF in Chlamydomonas decreased the reactive oxygen species (ROS) level and enhanced tolerance to heat stress. In addition to PETF, an endogenous anaerobic induced FDX5 was overexpressed in transgenic Chlamydomonas lines here to address the possible functions of FDX5. All the independent FDX transgenic lines showed decreased cellular ROS levels and enhanced tolerance to heat and salt stresses. The transgenic Chlamydomonas lines accumulated more starch than the wild-type line and this effect increased almost three-fold in conditions of nitrogen depletion. Furthermore, the lipid content was higher in the transgenic lines than in the wild-type line, both with and without nitrogen depletion. Two FDX-overexpressing Chlamydomonas lines were assessed in a photo microbial fuel cell (PMFC); power density production by the transgenic lines was higher than that of the wild-type cells. These findings suggest that overexpression of either PETF or FDX5 can confer tolerance against heat and salt stresses, increase starch and oil production, and raise electric power density in a PMFC. PMID- 26287180 TI - Identification of Proteins Modulated in the Date Palm Stem Infested with Red Palm Weevil (Rhynchophorus ferrugineus Oliv.) Using Two Dimensional Differential Gel Electrophoresis and Mass Spectrometry. AB - A state of the art proteomic methodology using Matrix Assisted Laser Desorption/Ionization-Time of Flight (MALDI TOF) has been employed to characterize peptides modulated in the date palm stem subsequent to infestation with red palm weevil (RPW). Our analyses revealed 32 differentially expressed peptides associated with RPW infestation in date palm stem. To identify RPW infestation associated peptides (I), artificially wounded plants (W) were used as additional control beside uninfested plants, a conventional control (C). A constant unique pattern of differential expression in infested (I), wounded (W) stem samples compared to control (C) was observed. The upregulated proteins showed relative fold intensity in order of I > W and downregulated spots trend as W > I, a quite interesting pattern. This study also reveals that artificially wounding of date palm stem affects almost the same proteins as infestation; however, relative intensity is quite lower than in infested samples both in up and downregulated spots. All 32 differentially expressed spots were subjected to MALDI-TOF analysis for their identification and we were able to match 21 proteins in the already existing databases. Relatively significant modulated expression pattern of a number of peptides in infested plants predicts the possibility of developing a quick and reliable molecular methodology for detecting plants infested with date palm. PMID- 26287177 TI - Disease Resistance Gene Analogs (RGAs) in Plants. AB - Plants have developed effective mechanisms to recognize and respond to infections caused by pathogens. Plant resistance gene analogs (RGAs), as resistance (R) gene candidates, have conserved domains and motifs that play specific roles in pathogens' resistance. Well-known RGAs are nucleotide binding site leucine rich repeats, receptor like kinases, and receptor like proteins. Others include pentatricopeptide repeats and apoplastic peroxidases. RGAs can be detected using bioinformatics tools based on their conserved structural features. Thousands of RGAs have been identified from sequenced plant genomes. High-density genome-wide RGA genetic maps are useful for designing diagnostic markers and identifying quantitative trait loci (QTL) or markers associated with plant disease resistance. This review focuses on recent advances in structures and mechanisms of RGAs, and their identification from sequenced genomes using bioinformatics tools. Applications in enhancing fine mapping and cloning of plant disease resistance genes are also discussed. PMID- 26287181 TI - GC-MS-Based Metabonomic Profiling Displayed Differing Effects of Borna Disease Virus Natural Strain Hu-H1 and Laboratory Strain V Infection in Rat Cortical Neurons. AB - Borna disease virus (BDV) persists in the central nervous systems of a wide variety of vertebrates and causes behavioral disorders. Previous studies have revealed that metabolic perturbations are associated with BDV infection. However, the pathophysiological effects of different viral strains remain largely unknown. Rat cortical neurons infected with human strain BDV Hu-H1, laboratory BDV Strain V, and non-infected control (CON) cells were cultured in vitro. At day 12 post infection, a gas chromatography coupled with mass spectrometry (GC-MS) metabonomic approach was used to differentiate the metabonomic profiles of 35 independent intracellular samples from Hu-H1-infected cells (n = 12), Strain V infected cells (n = 12), and CON cells (n = 11). Partial least squares discriminant analysis (PLS-DA) was performed to demonstrate discrimination between the three groups. Further statistical testing determined which individual metabolites displayed significant differences between groups. PLS-DA demonstrated that the whole metabolic pattern enabled statistical discrimination between groups. We identified 31 differential metabolites in the Hu-H1 and CON groups (21 decreased and 10 increased in Hu-H1 relative to CON), 35 differential metabolites in the Strain V and CON groups (30 decreased and 5 increased in Strain V relative to CON), and 21 differential metabolites in the Hu-H1 and Strain V groups (8 decreased and 13 increased in Hu-H1 relative to Strain V). Comparative metabonomic profiling revealed divergent perturbations in key energy and amino acid metabolites between natural strain Hu-H1 and laboratory Strain V of BDV. The two BDV strains differentially alter metabolic pathways of rat cortical neurons in vitro. Their systematic classification provides a valuable template for improved BDV strain definition in future studies. PMID- 26287182 TI - DNA Targeting Sequence Improves Magnetic Nanoparticle-Based Plasmid DNA Transfection Efficiency in Model Neurons. AB - Efficient non-viral plasmid DNA transfection of most stem cells, progenitor cells and primary cell lines currently presents an obstacle for many applications within gene therapy research. From a standpoint of efficiency and cell viability, magnetic nanoparticle-based DNA transfection is a promising gene vectoring technique because it has demonstrated rapid and improved transfection outcomes when compared to alternative non-viral methods. Recently, our research group introduced oscillating magnet arrays that resulted in further improvements to this novel plasmid DNA (pDNA) vectoring technology. Continued improvements to nanomagnetic transfection techniques have focused primarily on magnetic nanoparticle (MNP) functionalization and transfection parameter optimization: cell confluence, growth media, serum starvation, magnet oscillation parameters, etc. Noting that none of these parameters can assist in the nuclear translocation of delivered pDNA following MNP-pDNA complex dissociation in the cell's cytoplasm, inclusion of a cassette feature for pDNA nuclear translocation is theoretically justified. In this study incorporation of a DNA targeting sequence (DTS) feature in the transfecting plasmid improved transfection efficiency in model neurons, presumably from increased nuclear translocation. This observation became most apparent when comparing the response of the dividing SH-SY5Y precursor cell to the non-dividing and differentiated SH-SY5Y neuroblastoma cells. PMID- 26287183 TI - 15,16-Dihydrotanshinone I from the Functional Food Salvia miltiorrhiza Exhibits Anticancer Activity in Human HL-60 Leukemia Cells: in Vitro and in Vivo Studies. AB - 15,16-Dihydrotanshinone I (DHTS) is extracted from Salvia miltiorrhiza Bunge which is a functional food in Asia. In this study, we investigated the apoptotic effect of DHTS on the human acute myeloid leukemia (AML) type III HL-60 cell line. We found that treatment with 1.5 MUg/mL DHTS increased proapoptotic Bax and Bad protein expressions and activated caspases-3, -8, and -9, thus leading to poly ADP ribose polymerase (PARP) cleavage and resulting in cell apoptosis. DHTS induced sustained c-Jun N-terminal kinase (JNK) phosphorylation and Fas ligand (FasL) expression. The anti-Fas blocking antibody reversed the DHTS-induced cell death, and the JNK-specific inhibitor, SP600125, inhibited DHTS-induced caspase 3, -8, -9, and PARP cleavage. In a xenograft nude mice model, 25 mg/kg DHTS showed a great effect in attenuating HL-60 tumor growth. Taken together, these results suggest that DHTS can induce HL-60 cell apoptosis in vitro and inhibit HL 60 cell growth in vivo; the underlying mechanisms might be mediated through activation of the JNK and FasL signal pathways. PMID- 26287184 TI - Methyl Sartortuoate Inhibits Colon Cancer Cell Growth by Inducing Apoptosis and G2/M-Phase Arrest. AB - The potential anti-neoplastic activity of terpenoids is of continued interest. In this study, we investigate whether methyl sartortuoate, a terpenoid isolated from soft coral, induced cell cycle arrest and apoptosis in a human colon cancer cell line. Culture studies found that methyl sartortuoate inhibited colon cancer cell (LoVo and RKO) growth and caused apoptotic death in a concentration- and time dependent manner, by activation of caspase-8, caspase-9, caspase-3, p53 and Bax, and inactivation of B-cell lymphoma 2 (Bcl-2) apoptosis regulating proteins. Methyl sartortuoate treatment led to reduced expression of cdc2 and up-regulated p21 and p53, suggesting that Methyl sartortuoate induced G2-M arrest through modulation of p53/p21/cdc2 pathways. Methyl sartortuoate also up-regulated phospho-JNK and phospho-p38 expression levels. This resulted in cell cycle arrest at the G2-M phase and apoptosis in LoVo and RKO cells. Treatment with the JNK inhibitor SP600125 and the p38 MAPK inhibitor SB203580 prevented methyl sartortuoate-induced apoptosis in LoVo cells. Moreover, methyl sartortuoate also prevented neoplasm growth in NOD-SCID nude mice inoculated with LoVo cells. Taken together, these findings suggest that methyl sartortuoate is capable of leading to activation of caspase-8, -9, -3, increasing p53 and Bax/Bcl-2 ratio apoptosis through MAPK-dependent apoptosis and results in G2-M phase arrest in LoVo and RKO cells. Thus, methyl sartortuoate may be a promising anticancer candidate. PMID- 26287185 TI - Lentiviral-Mediated Short Hairpin RNA Knockdown of MTDH Inhibits Cell Growth and Induces Apoptosis by Regulating the PTEN/AKT Pathway in Hepatocellular Carcinoma. AB - The activation of oncogenes and the loss of tumor suppressor genes are believed to play critical roles in the pathogenesis of human hepatocellular carcinoma (HCC). Metaherin(MTDH), also called astrocyte elevated gene-1 (AEG-1), is frequently amplified in a variety of cancers, but the roles of MTDH with regard to growth and apoptosis in HCC have not yet been studied. In the present study, we first analyzed the expression of MTDH in HCC samples. We found that MTDH protein levels are higher in most HCC cancerous tissues compared with their matched adjacent non-tumor tissues. Additionally, the MTDH mRNA was also higher inHCC tissues compared to their matched adjacent non-tumor tissues. Knockdown of the endogenous MTDH using small interfering RNA further showed that deficiency of MTDH suppressed cell growth and caused apoptosis in HCC cells. Knockdown MTDH promoted PTEN and p53 expression in HCC cells and inhibited AKT phosphorylation. Knockdown MTDH also inhibited tumor growth in vivo. All these results indicated that MTDH protein levels in most HCC tissues are higher than non-tumor tissues, and knockdown of MTDH inhibited growth and induced apoptosis in HCC cells through the activation of PTEN.Therefore, MTDH might be an effective targeted therapy gene for HCC. PMID- 26287186 TI - Molecular and Functional Characterization of Thioredoxin 1 from Korean Rose Bitterling (Rhodeus uyekii). AB - Thioredoxin is a multifunctional antioxidant enzyme that belongs to the reductase family. In this study, we cloned and characterized thioredoxin 1 cDNA from the Korean rose bitterling Rhodeus uyekii (RuTrx). The full-length RuTrx cDNA consists of 674 bp with a 324 nt open reading frame (ORF) encoding a 107 aa protein. The deduced RuTrx amino acid sequence indicated a characteristic redox active site, (31)WCGPC(35). Pairwise alignment revealed RuTrx amino acid identity (55.1%-83.2%) with orthologs from various species of mammalia, amphibia, fish and bird. Phylogenetic analysis was conducted to determine the evolutionary position of RuTrx. Expression analysis showed that RuTrx transcripts were present in all of the tissues examined, and was high in the hepatopancreas of R. uyekii. During early development, the expression of RuTrx transcripts was increased. Recombinant RuTrx protein (rRuTrx) was tested for its capacity to serve as an antioxidant enzyme using a metal-catalyzed oxidation (MCO) system. The ability of rRuTrx to protect against supercoiled DNA cleavage due to oxidative nicking increased in a dose-dependent manner. In Raw264.7 cells, Dihydroethidium (DHE) staining for ROS production indicated the antioxidant activity of rRuTrx. Together, these findings suggest that RuTrx may play a role in maintaining the redox state balance in Korean rose bitterling R. uyekii. PMID- 26287187 TI - Pyrosequencing-Based Assays for Rapid Detection of HER2 and HER3 Mutations in Clinical Samples Uncover an E332E Mutation Affecting HER3 in Retroperitoneal Leiomyosarcoma. AB - Mutations in Human Epidermal Growth Factor Receptors (HER) are associated with poor prognosis of several types of solid tumors. Although HER-mutation detection methods are currently available, such as Next-Generation Sequencing (NGS), alternative pyrosequencing allow the rapid characterization of specific mutations. We developed specific PCR-based pyrosequencing assays for identification of most prevalent HER2 and HER3 mutations, including S310F/Y, R678Q, L755M/P/S/W, V777A/L/M, 774-776 insertion, and V842I mutations in HER2, as well as M91I, V104M/L, D297N/V/Y, and E332E/K mutations in HER3. We tested 85 Formalin Fixed and Paraffin Embbeded (FFPE) samples and we detected three HER2 V842I mutations in colorectal carcinoma (CRC), ovarian carcinoma, and pancreatic carcinoma patients, respectively, and a HER2-L755M mutation in a CRC specimen. We also determined the presence of a HER3-E332K mutation in an urothelial carcinoma sample, and two HER3-D297Y mutations, in both gastric adenocarcinoma and CRC specimens. The D297Y mutation was previously detected in breast and gastric tumors, but not in CRC. Moreover, we found a not-previously-described HER3-E332E synonymous mutation in a retroperitoneal leiomyosarcoma patient. The pyrosequencing assays presented here allow the detection and characterization of specific HER2 and HER3 mutations. These pyrosequencing assays might be implemented in routine diagnosis for molecular characterization of HER2/HER3 receptors as an alternative to complex NGS approaches. PMID- 26287189 TI - A Distributed Data-Gathering Protocol Using AUV in Underwater Sensor Networks. AB - In this paper, we propose a distributed data-gathering scheme using an autonomous underwater vehicle (AUV) working as a mobile sink to gather data from a randomly distributed underwater sensor network where sensor nodes are clustered around several cluster headers. Unlike conventional data-gathering schemes where the AUV visits either every node or every cluster header, the proposed scheme allows the AUV to visit some selected nodes named path-nodes in a way that reduces the overall transmission power of the sensor nodes. Monte Carlo simulations are performed to investigate the performance of the proposed scheme compared with several preexisting techniques employing the AUV in terms of total amount of energy consumption, standard deviation of each node's energy consumption, latency to gather data at a sink, and controlling overhead. Simulation results show that the proposed scheme not only reduces the total energy consumption but also distributes the energy consumption more uniformly over the network, thereby increasing the lifetime of the network. PMID- 26287190 TI - Mass Detection in Viscous Fluid Utilizing Vibrating Micro- and Nanomechanical Mass Sensors under Applied Axial Tensile Force. AB - Vibrating micro- and nanomechanical mass sensors are capable of quantitatively determining attached mass from only the first three (two) measured cantilever (suspended) resonant frequencies. However, in aqueous solutions that are relevant to most biological systems, the mass determination is challenging because the quality factor (Q-factor) due to fluid damping decreases and, as a result, usually just the fundamental resonant frequencies can be correctly identified. Moreover, for higher modes the resonance coupling, noise, and internal damping have been proven to strongly affect the measured resonances and, correspondingly, the accuracy of estimated masses. In this work, a technique capable of determining the mass for the cantilever and also the position of nanobeads attached on the vibrating micro-/nanomechanical beam under intentionally applied axial tensile force from the measured fundamental flexural resonant frequencies is proposed. The axial force can be created and controlled through an external electrostatic or magnetostatic field. Practicality of the proposed technique is confirmed on the suspended multi-walled carbon nanotube and the rectangular silicon cantilever-based mass sensors. We show that typically achievable force resolution has a negligibly small impact on the accuracy of mass measurement. PMID- 26287188 TI - Mitochondrial and Ubiquitin Proteasome System Dysfunction in Ageing and Disease: Two Sides of the Same Coin? AB - Mitochondrial dysfunction and impairment of the ubiquitin proteasome system have been described as two hallmarks of the ageing process. Additionally, both systems have been implicated in the etiopathogenesis of many age-related diseases, particularly neurodegenerative disorders, such as Alzheimer's and Parkinson's disease. Interestingly, these two systems are closely interconnected, with the ubiquitin proteasome system maintaining mitochondrial homeostasis by regulating organelle dynamics, the proteome, and mitophagy, and mitochondrial dysfunction impairing cellular protein homeostasis by oxidative damage. Here, we review the current literature and argue that the interplay of the two systems should be considered in order to better understand the cellular dysfunction observed in ageing and age-related diseases. Such an approach may provide valuable insights into molecular mechanisms underlying the ageing process, and further discovery of treatments to counteract ageing and its associated diseases. Furthermore, we provide a hypothetical model for the heterogeneity described among individuals during ageing. PMID- 26287191 TI - An Energy-Efficient Spectrum-Aware Reinforcement Learning-Based Clustering Algorithm for Cognitive Radio Sensor Networks. AB - It is well-known that clustering partitions network into logical groups of nodes in order to achieve energy efficiency and to enhance dynamic channel access in cognitive radio through cooperative sensing. While the topic of energy efficiency has been well investigated in conventional wireless sensor networks, the latter has not been extensively explored. In this paper, we propose a reinforcement learning-based spectrum-aware clustering algorithm that allows a member node to learn the energy and cooperative sensing costs for neighboring clusters to achieve an optimal solution. Each member node selects an optimal cluster that satisfies pairwise constraints, minimizes network energy consumption and enhances channel sensing performance through an exploration technique. We first model the network energy consumption and then determine the optimal number of clusters for the network. The problem of selecting an optimal cluster is formulated as a Markov Decision Process (MDP) in the algorithm and the obtained simulation results show convergence, learning and adaptability of the algorithm to dynamic environment towards achieving an optimal solution. Performance comparisons of our algorithm with the Groupwise Spectrum Aware (GWSA)-based algorithm in terms of Sum of Square Error (SSE), complexity, network energy consumption and probability of detection indicate improved performance from the proposed approach. The results further reveal that an energy savings of 9% and a significant Primary User (PU) detection improvement can be achieved with the proposed approach. PMID- 26287192 TI - Antigen-Antibody Affinity for Dry Eye Biomarkers by Label Free Biosensing. Comparison with the ELISA Technique. AB - The specificity and affinity of antibody-antigen interactions is a fundamental way to achieve reliable biosensing responses. Different proteins involved with dry eye dysfunction: ANXA1, ANXA11, CST4, PRDX5, PLAA and S100A6; were validated as biomarkers. In this work several antibodies were tested for ANXA1, ANXA11 and PRDX5 to select the best candidates for each biomarker. The results were obtained by using Biophotonic Sensing Cells (BICELLs) as an efficient methodology for label-free biosensing and compared with the Enzyme-Linked Immuno Sorbent Assay (ELISA) technique. PMID- 26287193 TI - An Efficient VLSI Architecture for Multi-Channel Spike Sorting Using a Generalized Hebbian Algorithm. AB - A novel VLSI architecture for multi-channel online spike sorting is presented in this paper. In the architecture, the spike detection is based on nonlinear energy operator (NEO), and the feature extraction is carried out by the generalized Hebbian algorithm (GHA). To lower the power consumption and area costs of the circuits, all of the channels share the same core for spike detection and feature extraction operations. Each channel has dedicated buffers for storing the detected spikes and the principal components of that channel. The proposed circuit also contains a clock gating system supplying the clock to only the buffers of channels currently using the computation core to further reduce the power consumption. The architecture has been implemented by an application specific integrated circuit (ASIC) with 90-nm technology. Comparisons to the existing works show that the proposed architecture has lower power consumption and hardware area costs for real-time multi-channel spike detection and feature extraction. PMID- 26287194 TI - Simultaneous Localization and Mapping with Iterative Sparse Extended Information Filter for Autonomous Vehicles. AB - In this paper, a novel iterative sparse extended information filter (ISEIF) was proposed to solve the simultaneous localization and mapping problem (SLAM), which is very crucial for autonomous vehicles. The proposed algorithm solves the measurement update equations with iterative methods adaptively to reduce linearization errors. With the scalability advantage being kept, the consistency and accuracy of SEIF is improved. Simulations and practical experiments were carried out with both a land car benchmark and an autonomous underwater vehicle. Comparisons between iterative SEIF (ISEIF), standard EKF and SEIF are presented. All of the results convincingly show that ISEIF yields more consistent and accurate estimates compared to SEIF and preserves the scalability advantage over EKF, as well. PMID- 26287195 TI - Efficient Sparse Signal Transmission over a Lossy Link Using Compressive Sensing. AB - Reliable data transmission over lossy communication link is expensive due to overheads for error protection. For signals that have inherent sparse structures, compressive sensing (CS) is applied to facilitate efficient sparse signal transmissions over lossy communication links without data compression or error protection. The natural packet loss in the lossy link is modeled as a random sampling process of the transmitted data, and the original signal will be reconstructed from the lossy transmission results using the CS-based reconstruction method at the receiving end. The impacts of packet lengths on transmission efficiency under different channel conditions have been discussed, and interleaving is incorporated to mitigate the impact of burst data loss. Extensive simulations and experiments have been conducted and compared to the traditional automatic repeat request (ARQ) interpolation technique, and very favorable results have been observed in terms of both accuracy of the reconstructed signals and the transmission energy consumption. Furthermore, the packet length effect provides useful insights for using compressed sensing for efficient sparse signal transmission via lossy links. PMID- 26287197 TI - Underwater Acoustic Wavefront Visualization by Scanning Laser Doppler Vibrometer for the Characterization of Focused Ultrasonic Transducers. AB - The analysis of acoustic wave fields is important for a large number of engineering designs, communication and health-related reasons. The visualization of wavefronts gives valuable information about the type of transducers and excitation signals more suitable for the test itself. This article is dedicated to the development of a fast procedure for acoustic fields visualization in underwater conditions, by means of laser Doppler vibrometer measurements. The ultrasonic probe is a focused transducer excited by a chirp signal. The scope of this work is to evaluate experimentally the properties of the sound beam in order to get reliable information about the transducer itself to be used in many kinds of engineering tests and transducer design. PMID- 26287196 TI - Quadruplex Integrated DNA (QuID) Nanosensors for Monitoring Dopamine. AB - Dopamine is widely innervated throughout the brain and critical for many cognitive and motor functions. Imbalances or loss in dopamine transmission underlie various psychiatric disorders and degenerative diseases. Research involving cellular studies and disease states would benefit from a tool for measuring dopamine transmission. Here we show a Quadruplex Integrated DNA (QuID) nanosensor platform for selective and dynamic detection of dopamine. This nanosensor exploits DNA technology and enzyme recognition systems to optically image dopamine levels. The DNA quadruplex architecture is designed to be compatible in physically constrained environments (110 nm) with high flexibility, homogeneity, and a lower detection limit of 110 uM. PMID- 26287198 TI - A Fast Robot Identification and Mapping Algorithm Based on Kinect Sensor. AB - Internet of Things (IoT) is driving innovation in an ever-growing set of application domains such as intelligent processing for autonomous robots. For an autonomous robot, one grand challenge is how to sense its surrounding environment effectively. The Simultaneous Localization and Mapping with RGB-D Kinect camera sensor on robot, called RGB-D SLAM, has been developed for this purpose but some technical challenges must be addressed. Firstly, the efficiency of the algorithm cannot satisfy real-time requirements; secondly, the accuracy of the algorithm is unacceptable. In order to address these challenges, this paper proposes a set of novel improvement methods as follows. Firstly, the ORiented Brief (ORB) method is used in feature detection and descriptor extraction. Secondly, a bidirectional Fast Library for Approximate Nearest Neighbors (FLANN) k-Nearest Neighbor (KNN) algorithm is applied to feature match. Then, the improved RANdom SAmple Consensus (RANSAC) estimation method is adopted in the motion transformation. In the meantime, high precision General Iterative Closest Points (GICP) is utilized to register a point cloud in the motion transformation optimization. To improve the accuracy of SLAM, the reduced dynamic covariance scaling (DCS) algorithm is formulated as a global optimization problem under the G2O framework. The effectiveness of the improved algorithm has been verified by testing on standard data and comparing with the ground truth obtained on Freiburg University's datasets. The Dr Robot X80 equipped with a Kinect camera is also applied in a building corridor to verify the correctness of the improved RGB-D SLAM algorithm. With the above experiments, it can be seen that the proposed algorithm achieves higher processing speed and better accuracy. PMID- 26287199 TI - Porous Silicon Structures as Optical Gas Sensors. AB - We present a short review of recent progress in the field of optical gas sensors based on porous silicon (PSi) and PSi composites, which are separate from PSi optochemical and biological sensors for a liquid medium. Different periodical and nonperiodical PSi photonic structures (bares, modified by functional groups or infiltrated with sensory polymers) are described for gas sensing with an emphasis on the device specificity, sensitivity and stability to the environment. Special attention is paid to multiparametric sensing and sensor array platforms as effective trends for the improvement of analyte classification and quantification. Mechanisms of gas physical and chemical sorption inside PSi mesopores and pores of PSi functional composites are discussed. PMID- 26287200 TI - Damage Detection Based on Static Strain Responses Using FBG in a Wind Turbine Blade. AB - The damage detection of a wind turbine blade enables better operation of the turbines, and provides an early alert to the destroyed events of the blade in order to avoid catastrophic losses. A new non-baseline damage detection method based on the Fiber Bragg grating (FBG) in a wind turbine blade is developed in this paper. Firstly, the Chi-square distribution is proven to be an effective damage-sensitive feature which is adopted as the individual information source for the local decision. In order to obtain the global and optimal decision for the damage detection, the feature information fusion (FIF) method is proposed to fuse and optimize information in above individual information sources, and the damage is detected accurately through of the global decision. Then a 13.2 m wind turbine blade with the distributed strain sensor system is adopted to describe the feasibility of the proposed method, and the strain energy method (SEM) is used to describe the advantage of the proposed method. Finally results show that the proposed method can deliver encouraging results of the damage detection in the wind turbine blade. PMID- 26287201 TI - Visual Sensing for Urban Flood Monitoring. AB - With the increasing climatic extremes, the frequency and severity of urban flood events have intensified worldwide. In this study, image-based automated monitoring of flood formation and analyses of water level fluctuation were proposed as value-added intelligent sensing applications to turn a passive monitoring camera into a visual sensor. Combined with the proposed visual sensing method, traditional hydrological monitoring cameras have the ability to sense and analyze the local situation of flood events. This can solve the current problem that image-based flood monitoring heavily relies on continuous manned monitoring. Conventional sensing networks can only offer one-dimensional physical parameters measured by gauge sensors, whereas visual sensors can acquire dynamic image information of monitored sites and provide disaster prevention agencies with actual field information for decision-making to relieve flood hazards. The visual sensing method established in this study provides spatiotemporal information that can be used for automated remote analysis for monitoring urban floods. This paper focuses on the determination of flood formation based on image-processing techniques. The experimental results suggest that the visual sensing approach may be a reliable way for determining the water fluctuation and measuring its elevation and flood intrusion with respect to real-world coordinates. The performance of the proposed method has been confirmed; it has the capability to monitor and analyze the flood status, and therefore, it can serve as an active flood warning system. PMID- 26287203 TI - Measurement Model and Precision Analysis of Accelerometers for Maglev Vibration Isolation Platforms. AB - High precision measurement of acceleration levels is required to allow active control for vibration isolation platforms. It is necessary to propose an accelerometer configuration measurement model that yields such a high measuring precision. In this paper, an accelerometer configuration to improve measurement accuracy is proposed. The corresponding calculation formulas of the angular acceleration were derived through theoretical analysis. A method is presented to minimize angular acceleration noise based on analysis of the root mean square noise of the angular acceleration. Moreover, the influence of installation position errors and accelerometer orientation errors on the calculation precision of the angular acceleration is studied. Comparisons of the output differences between the proposed configuration and the previous planar triangle configuration under the same installation errors are conducted by simulation. The simulation results show that installation errors have a relatively small impact on the calculation accuracy of the proposed configuration. To further verify the high calculation precision of the proposed configuration, experiments are carried out for both the proposed configuration and the planar triangle configuration. On the basis of the results of simulations and experiments, it can be concluded that the proposed configuration has higher angular acceleration calculation precision and can be applied to different platforms. PMID- 26287204 TI - Gas-Sensing Performance of M-Doped CuO-Based Thin Films Working at Different Temperatures upon Exposure to Propane. AB - Cupric oxide (CuO) thin films are promising materials in gas sensor applications. The CuO-based gas sensors behaved as p-type semiconductors and can be used as part of an e-nose or smart sensor array for breath analysis. The authors present the investigation results on M-doped CuO-based (M = Ag, Au, Cr, Pd, Pt, Sb, Si) sensors working at various temperatures upon exposure to a low concentration of C3H8, which can be found in exhaled human breath, and it can be considered as a one of the biomarkers of several diseases. The films have been deposited in magnetron sputtering technology on low temperature cofired ceramics substrates. The results of the gas sensors' response are also presented and discussed. The Cr:CuO-based structure, annealed at 400 degrees C for 4 h in air, showed the highest sensor response, of the order of 2.7 at an operation temperature of 250 degrees C. The response and recovery time(s) were 10 s and 24 s, respectively. The results show that the addition of M-dopants in the cupric oxide films effectively act as catalysts in propane sensors and improve the gas sensing properties. The films' phase composition, microstructure and surface topography have been assessed by the X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) methods. PMID- 26287202 TI - Designing a Microfluidic Device with Integrated Ratiometric Oxygen Sensors for the Long-Term Control and Monitoring of Chronic and Cyclic Hypoxia. AB - Control of oxygen over cell cultures in vitro is a topic of considerable interest, as chronic and cyclic hypoxia can alter cell behaviour. Both static and transient hypoxic levels have been found to affect tumour cell behaviour; it is potentially valuable to include these effects in early, in vitro stages of drug screening. A barrier to their inclusion is that rates of transient hypoxia can be a few cycles/hour, which is difficult to reproduce in traditional in vitro cell culture environments due to long diffusion distances from control gases to the cells. We use a gas-permeable three-layer microfluidic device to achieve spatial and temporal oxygen control with biologically-relevant switching times. We measure the oxygen profiles with integrated, ratiometric optical oxygen sensors, demonstrate sensor and system stability over multi-day experiments, and characterize a pre-bleaching process to improve sensor stability. We show, with both finite-element modelling and experimental data, excellent control over the oxygen levels by the device, independent of fluid flow rate and oxygenation for the operating flow regime. We measure equilibration times of approximately 10 min, generate complex, time-varying oxygen profiles, and study the effects of oxygenated media flow rates on the measured oxygen levels. This device could form a useful tool for future long-term studies of cell behaviour under hypoxia. PMID- 26287205 TI - Ag-Modified In2O3/ZnO Nanobundles with High Formaldehyde Gas-Sensing Performance. AB - Ag-modified In2O3/ZnO bundles with micro/nano porous structures have been designed and synthesized with by hydrothermal method continuing with dehydration process. Each bundle consists of nanoparticles, where nanogaps of 10-30 nm are present between the nanoparticles, leading to a porous structure. This porous structure brings high surface area and fast gas diffusion, enhancing the gas sensitivity. Consequently, the HCHO gas-sensing performance of the Ag-modified In2O3/ZnO bundles have been tested, with the formaldehyde-detection limit of 100 ppb (parts per billion) and the response and recover times as short as 6 s and 3 s, respectively, at 300 degrees C and the detection limit of 100 ppb, response time of 12 s and recover times of 6 s at 100 degrees C. The HCHO sensing detect limitation matches the health standard limitation on the concentration of formaldehyde for indoor air. Moreover, the strategy to synthesize the nanobundles is just two-step heating and easy to scale up. Therefore, the Ag-modified In2O3/ZnO bundles are ready for industrialization and practical applications. PMID- 26287206 TI - A Framework to Automate Assessment of Upper-Limb Motor Function Impairment: A Feasibility Study. AB - Standard upper-limb motor function impairment assessments, such as the Fugl-Meyer Assessment (FMA), are a critical aspect of rehabilitation after neurological disorders. These assessments typically take a long time (about 30 min for the FMA) for a clinician to perform on a patient, which is a severe burden in a clinical environment. In this paper, we propose a framework for automating upper limb motor assessments that uses low-cost sensors to collect movement data. The sensor data is then processed through a machine learning algorithm to determine a score for a patient's upper-limb functionality. To demonstrate the feasibility of the proposed approach, we implemented a system based on the proposed framework that can automate most of the FMA. Our experiment shows that the system provides similar FMA scores to clinician scores, and reduces the time spent evaluating each patient by 82%. Moreover, the proposed framework can be used to implement customized tests or tests specified in other existing standard assessment methods. PMID- 26287207 TI - Review of Trackside Monitoring Solutions: From Strain Gages to Optical Fibre Sensors. AB - A review of recent research on structural monitoring in railway industry is proposed in this paper, with a special focus on stress-based solutions. After a brief analysis of the mechanical behaviour of ballasted railway tracks, an overview of the most common monitoring techniques is presented. A special attention is paid on strain gages and accelerometers for which the accurate mounting position on the track is requisite. These types of solution are then compared to another modern approach based on the use of optical fibres. Besides, an in-depth discussion is made on the evolution of numerical models that investigate the interaction between railway vehicles and tracks. These models are used to validate experimental devices and to predict the best location(s) of the sensors. It is hoped that this review article will stimulate further research activities in this continuously expanding field. PMID- 26287208 TI - A Microgripper with a Post-Assembly Self-Locking Mechanism. AB - In this work, we report a new design for an electrostatically actuated microgripper with a post-assembly self-locking mechanism. The microgripper arms are driven by rotary comb actuators, enabling the microgripper to grip objects of any size from 0 to 100 MUm. The post-assembly mechanism is driven by elastic deformation energy and static electricity to produce self-locking and releasing actions. The mechanism enables the microgripper arms to grip for long periods without continuously applying the external driving signal, which significantly reduces the effects and damage to the gripped objects caused by these external driving signals. The microgripper was fabricated using a Silicon-On-Insulator (SOI) wafer with a 30 MUm structural layer. Test results show that this gripper achieves a displacement of 100 MUm with a driving voltage of 33 V, and a metal wire with a diameter of about 1.6 mil is successfully gripped to demonstrate the feasibility of this post-assembly self-locking mechanism. PMID- 26287209 TI - A Charrelation Matrix-Based Blind Adaptive Detector for DS-CDMA Systems. AB - In this paper, a blind adaptive detector is proposed for blind separation of user signals and blind estimation of spreading sequences in DS-CDMA systems. The blind separation scheme exploits a charrelation matrix for simple computation and effective extraction of information from observation signal samples. The system model of DS-CDMA signals is modeled as a blind separation framework. The unknown user information and spreading sequence of DS-CDMA systems can be estimated only from the sampled observation signals. Theoretical analysis and simulation results show that the improved performance of the proposed algorithm in comparison with the existing conventional algorithms used in DS-CDMA systems. Especially, the proposed scheme is suitable for when the number of observation samples is less and the signal to noise ratio (SNR) is low. PMID- 26287210 TI - Control Parameters Optimization Based on Co-Simulation of a Mechatronic System for an UA-Based Two-Axis Inertially Stabilized Platform. AB - This paper presents a method based on co-simulation of a mechatronic system to optimize the control parameters of a two-axis inertially stabilized platform system (ISP) applied in an unmanned airship (UA), by which high control performance and reliability of the ISP system are achieved. First, a three dimensional structural model of the ISP is built by using the three-dimensional parametric CAD software SOLIDWORKS((r)); then, to analyze the system's kinematic and dynamic characteristics under operating conditions, dynamics modeling is conducted by using the multi-body dynamics software ADAMSTM, thus the main dynamic parameters such as displacement, velocity, acceleration and reaction curve are obtained, respectively, through simulation analysis. Then, those dynamic parameters were input into the established MATLAB((r)) SIMULINK((r)) controller to simulate and test the performance of the control system. By these means, the ISP control parameters are optimized. To verify the methods, experiments were carried out by applying the optimized parameters to the control system of a two-axis ISP. The results show that the co-simulation by using virtual prototyping (VP) is effective to obtain optimized ISP control parameters, eventually leading to high ISP control performance. PMID- 26287211 TI - Nano-Enriched and Autonomous Sensing Framework for Dissolved Oxygen. AB - This paper investigates a nano-enhanced wireless sensing framework for dissolved oxygen (DO). The system integrates a nanosensor that employs cerium oxide (ceria) nanoparticles to monitor the concentration of DO in aqueous media via optical fluorescence quenching. We propose a comprehensive sensing framework with the nanosensor equipped with a digital interface where the sensor output is digitized and dispatched wirelessly to a trustworthy data collection and analysis framework for consolidation and information extraction. The proposed system collects and processes the sensor readings to provide clear indications about the current or the anticipated dissolved oxygen levels in the aqueous media. PMID- 26287212 TI - Antifungal Activity of 14-Helical beta-Peptides against Planktonic Cells and Biofilms of Candida Species. AB - Candida albicans is the most prevalent cause of fungal infections and treatment is further complicated by the formation of drug resistant biofilms, often on the surfaces of implanted medical devices. In recent years, the incidence of fungal infections by other pathogenic Candida species such as C. glabrata, C. parapsilosis and C. tropicalis has increased. Amphiphilic, helical beta-peptide structural mimetics of natural antimicrobial alpha-peptides have been shown to exhibit specific planktonic antifungal and anti-biofilm formation activity against C. albicans in vitro. Here, we demonstrate that beta-peptides are also active against clinically isolated and drug resistant strains of C. albicans and against other opportunistic Candida spp. Different Candida species were susceptible to beta-peptides to varying degrees, with C. tropicalis being the most and C. glabrata being the least susceptible. beta-peptide hydrophobicity directly correlated with antifungal activity against all the Candida clinical strains and species tested. While beta-peptides were largely ineffective at disrupting existing Candida biofilms, hydrophobic beta-peptides were able to prevent the formation of C. albicans, C. glabrata, C. parapsilosis and C. tropicalis biofilms. The broad-spectrum antifungal activity of beta-peptides against planktonic cells and in preventing biofilm formation suggests the promise of this class of molecules as therapeutics. PMID- 26287215 TI - Chemistry of Renieramycins. Part 14: Total Synthesis of Renieramycin I and Practical Synthesis of Cribrostatin 4 (Renieramycin H). AB - The first total synthesis of (+/-)-renieramycin I, which was isolated from the Indian bright blue sponge Haliclona cribricutis, is described. The key step is the selenium oxide oxidation of pentacyclic bis-p-quinone derivative (3) stereo- and regioselectively. We also report a large-scale synthesis of cribrostatin 4 (renieramycin H) via the C3-C4 double bond formation in an early stage based on the Avendano's protocol, from readily available 1-acetyl-3-(3-methyl-2,4,5 trimethylphenyl)methyl-piperazine-2,5-dione (8) in 18 steps (8.3% overall yield). The synthesis provides unambiguous evidence supporting the original structure of renieramycin I. PMID- 26287214 TI - Marine Indole Alkaloids. AB - Marine indole alkaloids comprise a large and steadily growing group of secondary metabolites. Their diverse biological activities make many compounds of this class attractive starting points for pharmaceutical development. Several marine derived indoles were found to possess cytotoxic, antineoplastic, antibacterial and antimicrobial activities, in addition to the action on human enzymes and receptors. The newly isolated indole alkaloids of marine origin since the last comprehensive review in 2003 are reported, and biological aspects will be discussed. PMID- 26287216 TI - Carotenoids from Marine Microalgae: A Valuable Natural Source for the Prevention of Chronic Diseases. AB - Epidemiological studies have shown a relation between antioxidants and the prevention of several chronic diseases. Microalgae are a potential novel source of bioactive molecules, including a wide range of different carotenoids that can be used as nutraceuticals, food supplements and novel food products. The objective of this review is (i) to update the research that has been carried out on the most known carotenoids produced by marine microalgae, including reporting on their high potentialities to produce other less known important compounds; (ii) to compile the work that has been done in order to establish some relationship between carotenoids and oxidative protection and treatment; (iii) to summarize the association of oxidative stress and the various reactive species including free radicals with several human diseases; and (iv) to provide evidence of the potential of carotenoids from marine microalgae to be used as therapeutics to treat or prevent these oxidative stress-related diseases. PMID- 26287218 TI - Hormaomycins B and C: New Antibiotic Cyclic Depsipeptides from a Marine Mudflat Derived Streptomyces sp. AB - Alterations in microbial culture conditions may trigger the production of diverse bioactive secondary metabolites. While applying various culture conditions and monitoring secondary metabolite profiles using LC/MS, hormaomycins B and C (1 and 2) were discovered from a marine mudflat-derived actinomycete, Streptomyces sp., collected in Mohang, Korea. The planar structures of the hormaomycins, which bear structurally-unique units, such as 4-(Z)-propenylproline, 3-(2 nitrocyclopropyl)alanine, 5-chloro-1-hydroxypyrrol-2-carboxylic acid and b methylphenylalanine, were established as the first natural analogues belonging to the hormaomycin peptide class. The absolute configurations of 1 and 2 were deduced by comparing their CD spectra with that of hormaomycin. These hormaomycins exhibited significant inhibitory effects against various pathogenic Gram-positive and Gram-negative bacteria. PMID- 26287217 TI - Chitosan: An Update on Potential Biomedical and Pharmaceutical Applications. AB - Chitosan is a natural polycationic linear polysaccharide derived from chitin. The low solubility of chitosan in neutral and alkaline solution limits its application. Nevertheless, chemical modification into composites or hydrogels brings to it new functional properties for different applications. Chitosans are recognized as versatile biomaterials because of their non-toxicity, low allergenicity, biocompatibility and biodegradability. This review presents the recent research, trends and prospects in chitosan. Some special pharmaceutical and biomedical applications are also highlighted. PMID- 26287219 TI - Impact of Point-of-Sale Tobacco Display Bans in Thailand: Findings from the International Tobacco Control (ITC) Southeast Asia Survey. AB - In September 2005 Thailand became the first Asian country to implement a complete ban on the display of cigarettes and other tobacco products at point-of-sale (POS). This paper examined the impact of the POS tobacco display ban in Thailand, with Malaysia (which did not impose bans) serving as a comparison. The data came from the International Tobacco Control Southeast Asia Survey (2005-2011), a prospective cohort survey designed to evaluate the psychosocial and behavioral impacts of tobacco control policies. Main measures included smokers' reported awareness of tobacco displays and advertising at POS. At the first post-ban survey wave over 90% of smokers in Thailand were aware of the display ban policy and supported it, and about three quarters thought the ban was effective. Noticing tobacco displays in stores was lowest (16.9%) at the first post-ban survey wave, but increased at later survey waves; however, the levels were consistently lower than those in Malaysia. Similarly, exposure to POS tobacco advertising was lower in Thailand. The display ban has reduced exposure to tobacco marketing at POS. The trend toward increased noticing is likely at least in part due to some increase in violations of the display bans and/or strategies to circumvent them. PMID- 26287220 TI - Estimating the Smoking Ban Effects on Smoking Prevalence, Quitting and Cigarette Consumption in a Population Study of Apprentices in Italy. AB - OBJECTIVES: We evaluated the effects of the Italian 2005 smoking ban in public places on the prevalence of smoking, quitting and cigarette consumption of young workers. DATA AND METHODS: The dataset was obtained from non-computerized registers of medical examinations for a population of workers with apprenticeship contracts residing in the province of Viterbo, Italy, in the period 1996-2007. To estimate the effects of the ban, a segmented regression approach was used, exploiting the discontinuity introduced by the application of the law on apprentices' smoking behavior. RESULTS: It is estimated that the Italian smoking ban generally had no effect on smoking prevalence, quitting ratio, or cigarette consumption of apprentices. However, when the estimates were applied to subpopulations, significant effects were found: -1% in smoking prevalence, +2% in quitting, and -3% in smoking intensity of apprentices with at least a diploma. PMID- 26287221 TI - Readiness Visual Analog Scale: A Simple Way to Predict Post-Stroke Smoking Behavior. AB - BACKGROUND AND PURPOSE: The aim of the present study was to assess a relationship between readiness to quit and post-stroke smoking behavior. METHODS: Eighty-six active smokers with first-ever ischemic stroke were recruited in a tertiary-care stroke unit. The question "Are you ready to quit smoking within the next month?" with yes/no responses and the 10-cm readiness visual analog scale (VAS) was administered during the anti-smoking intervention. Smoking status was verified at the 3- and 12-month follow-up. RESULTS: The readiness VAS score at hospitalization was significantly lower in patients classified as smokers as compared to patients classified as non-smokers. The readiness score <5 cm was a significant predictor of smoking at the 3-month (OR, 7.3) and 12-month follow-up (OR, 4.9). CONCLUSIONS: The present results suggest that the readiness VAS can be used as a simple and inexpensive instrument for early identification of patients who continue to smoke after stroke. PMID- 26287222 TI - Solar-Enhanced Advanced Oxidation Processes for Water Treatment: Simultaneous Removal of Pathogens and Chemical Pollutants. AB - The review explores the feasibility of simultaneous removal of pathogens and chemical pollutants by solar-enhanced advanced oxidation processes (AOPs). The AOPs are based on in-situ generation of reactive oxygen species (ROS), most notably hydroxyl radicals *OH, that are capable of destroying both pollutant molecules and pathogen cells. The review presents evidence of simultaneous removal of pathogens and chemical pollutants by photocatalytic processes, namely TiO2 photocatalysis and photo-Fenton. Complex water matrices with high loads of pathogens and chemical pollutants negatively affect the efficiency of disinfection and pollutant removal. This is due to competition between chemical substances and pathogens for generated ROS. Other possible negative effects include light screening, competitive photon absorption, adsorption on the catalyst surface (thereby inhibiting its photocatalytic activity), etc. Besides, some matrix components may serve as nutrients for pathogens, thus hindering the disinfection process. Each type of water/wastewater would require a tailor-made approach and the variables that were shown to influence the processes catalyst/oxidant concentrations, incident radiation flux, and pH-need to be adjusted in order to achieve the required degree of pollutant and pathogen removal. Overall, the solar-enhanced AOPs hold promise as an environmentally friendly way to substitute or supplement conventional water/wastewater treatment, particularly in areas without access to centralized drinking water or sewage/wastewater treatment facilities. PMID- 26287223 TI - Factors associated with Early Initiation of Breastfeeding in Western Nepal. AB - The initiation of breastfeeding within one hour of birth has numerous nutritional and immunological benefits and has been found to reduce neonatal mortality. This community-based prospective cohort study aimed to report the rate of, and factors associated with, early initiation of breastfeeding in Western Nepal. The rate of early initiation of breastfeeding was reported, and associations between early initiation and independent variables were tested by Chi-square test, followed by multiple logistic regression. Of the 735 mother-infant pairs, a total of 310 (42.2%) reported early initiation. Mothers who were assisted by traditional attendants during childbirth, delivered by caesarean section, from ethnically disadvantaged families and had delivered low birth weight infants, were less likely to initiate breastfeeding early whereas the mothers who were from the poorest families and did not introduce prelacteal feeds to their infants were more likely to initiate breastfeeding within the first hour. Skills-training to support breastfeeding as part of the training of skilled birth attendants and other health workers is likely to promote recommended infant feeding practices. PMID- 26287224 TI - Can Public Health Risk Assessment Using Risk Matrices Be Misleading? AB - The risk assessment matrix is a widely accepted, semi-quantitative tool for assessing risks, and setting priorities in risk management. Although the method can be useful to promote discussion to distinguish high risks from low risks, a published critique described a problem when the frequency and severity of risks are negatively correlated. A theoretical analysis showed that risk predictions could be misleading. We evaluated a practical public health example because it provided experiential risk data that allowed us to assess the practical implications of the published concern that risk matrices would make predictions that are worse than random. We explored this predicted problem by constructing a risk assessment matrix using a public health risk scenario-Tainted blood transfusion infection risk-That provides negative correlation between harm frequency and severity. We estimated the risk from the experiential data and compared these estimates with those provided by the risk assessment matrix. Although we validated the theoretical concern, for these authentic experiential data, the practical scope of the problem was limited. The risk matrix has been widely used in risk assessment. This method should not be abandoned wholesale, but users must address the source of the problem, apply the risk matrix with a full understanding of this problem and use matrix predictions to inform, but not drive decision-making. PMID- 26287225 TI - Oxidative Stress Mechanisms Caused by Ag Nanoparticles (NM300K) are Different from Those of AgNO3: Effects in the Soil Invertebrate Enchytraeus Crypticus. AB - The mechanisms of toxicity of Ag nanoparticles (NPs) are unclear, in particular in the terrestrial environment. In this study the effects of AgNP (AgNM300K) were assessed in terms of oxidative stress in the soil worm Enchytraeus crypticus, using a range of biochemical markers [catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR), total glutathione (TG), metallothionein (MT), lipid peroxidation (LPO)]. E. crypticus were exposed during 3 and 7 days (d) to the reproduction EC20, EC50 and EC80 levels of both AgNP and AgNO3. AgNO3 induced oxidative stress earlier (3 d) than AgNP (7 d), both leading to LPO despite the activation of the anti-redox system. MT increased only for AgNP. The Correspondence Analysis showed a clear separation between AgNO3 and AgNP, with e.g. CAT being the main descriptor for AgNP for 7 d. LPO, GST and GPx were for both 3 and 7 d associated with AgNO3, whereas MT and TG were associated with AgNP. These results may reflect a delay in the effects of AgNP compared to AgNO3 due to the slower release of Ag(+) ions from the AgNP, although this does not fully explain the observed differences, i.e., we can conclude that there is a nanoparticle effect. PMID- 26287226 TI - Seasonal Variation and Sources of Dissolved Nutrients in the Yellow River, China. AB - The rapid growth of the economy in China has caused dramatic growth in the industrial and agricultural development in the Yellow River (YR) watershed. The hydrology of the YR has changed dramatically due to the climate changes and water management practices, which have resulted in a great variation in the fluxes of riverine nutrients carried by the YR. To study these changes dissolved nutrients in the YR were measured monthly at Lijin station in the downstream region of the YR from 2002 to 2004. This study provides detailed information on the nutrient status for the relevant studies in the lower YR and the Bohai Sea. The YR was enriched in nitrate (average 314 MUmol.L(-1)) with a lower concentration of dissolved silicate (average 131 MUmol.L(-1)) and relatively low dissolved phosphate (average 0.35 MUmol.L(-1)). Nutrient concentrations exhibited substantial seasonal and yearly variations. The annual fluxes of dissolved inorganic nitrogen, phosphate, and silicate in 2004 were 5.3, 2.5, and 4.2 times those in 2002, respectively, primarily due to the increase in river discharge. The relative contributions of nutrient inputs to nitrogen in the YR were: wastewater > fertilizer > atmospheric deposition > soil; while to phosphorus were: wastewater > fertilizer > soil > atmospheric deposition. The ratios of N, P and Si suggest that the YR at Lijin is strongly P-limited with respect to potential phytoplankton growth. PMID- 26287227 TI - Study on the Adsorption Capacities for Airborne Particulates of Landscape Plants in Different Polluted Regions in Beijing (China). AB - Urban landscape plants are an important component of the urban ecosystem, playing a significant role in the adsorption of airborne particulates and air purification. In this study, six common landscape plants in Beijing were chosen as research subjects, and the adsorption capacities for each different plant leaf and the effects of the leaf structures for the adsorption capacities for particulates were determined. Preliminary results show that needle-leaved tree species adsorbed more airborne particulates than broad-leaved tree species for the same leaf area. Pinus tabuliformis exhibits the highest adsorption capacity, at 3.89 +/- 0.026 MUg.cm(-2), almost two times as much as that of Populus tomentosa (2.00 +/- 0.118 MUg.cm(-2)). The adsorption capacities for PM10 of the same tree species leaves, in different polluted regions had significant differences, and the adsorption capacities for PM10 of the tree species leaf beside the Fifth Ring Road were higher than those of the tree species leaves in the Botanical Garden, although the adsorption capacities for PM2.5 of the same tree species in different polluted regions had no significant differences. By determining the soluble ion concentrations of the airborne particulates in two regions, it is suggested that the soluble ion concentrations of PM10 in the atmosphere in the Botanical Garden and beside the Fifth Ring Road have significant differences, while those of PM2.5 in the atmosphere had no significant differences. In different polluted regions there are significant adaptive changes to the leaf structures, and when compared with slightly polluted region, in the seriously polluted region the epidermis cells of the plant leaves shrinked, the surface textures of the leaves became rougher, and the stomas' frequency and the pubescence length increased. Even though the plant leaves exposed to the seriously polluted region changed significantly, these plants can still grow normally and healthily. PMID- 26287228 TI - Prevalence of Polyherbacy in Ambulatory Visits to Traditional Chinese Medicine Clinics in Taiwan. AB - Patients with a polyherbal prescription are more likely to receive duplicate medications and thus suffer from adverse drug reactions. We conducted a population-based retrospective study to examine the items of Chinese herbal medicine (CHM) per prescription in the ambulatory care of traditional Chinese medicine (TCM) in Taiwan. We retrieved complete TCM ambulatory visit datasets for 2010 from the National Health Insurance database in Taiwan. A total of 59,790 patients who received 313,482 CHM prescriptions were analyzed. Drug prescriptions containing more than five drugs were classified as polyherbal prescriptions; 41.6% of patients were given a polyherbal prescription. There were on average 5.2 +/- 2.5 CHMs: 2.3 +/- 1.1 compound herbal formula items, and 3.0 +/- 2.5 single Chinese herb items in a single prescription. Approximately 4.6% of patients were prescribed 10 CHMs or more. Men had a lower odds ratio (OR) among polyherbal prescriptions (OR = 0.96, 95% confidence interval [CI] 0.92-0.99), and middle aged patients (35-49 years) had the highest frequency of polyherbal prescription (OR = 1.19, 95% CI = 1.13-1.26). Patients with neoplasm, skin and subcutaneous tissue disease, or genitourinary system disease were more likely to have a polyherbal prescription; OR = 2.20 (1.81-2.67), 1.65 (1.50-1.80), and 1.52 (1.40 1.64), respectively. Polyherbal prescription is widespread in TCM in Taiwan. Potential herb interactions and iatrogenic risks associated with polyherbal prescriptions should be monitored. PMID- 26287229 TI - Pollution Characteristics and Health Risk Assessment of Airborne Heavy Metals Collected from Beijing Bus Stations. AB - Airborne dust, which contains high levels of toxic metals, is recognized as one of the most harmful environment component. The purpose of this study was to evaluate heavy metals pollution in dustfall from bus stations in Beijing, and to perform a risk assessment analysis for adult passengers. The concentrations of Cd, Co, Cr, Cu, Mo, Ni, Pb, V and Zn were determined by inductively coupled plasma mass spectroscopy (ICP-MS). The spatial distribution, pollution level and potential health risk of heavy metals were analyzed by Geographic Information System (GIS) mapping technology, geo-accumulation index and health risk assessment model, respectively. The results indicate that dust samples have elevated metal concentrations, especially for Cd, Cu, Pb and Zn. The nine metals can be divided into two categories in terms of spatial distribution and pollution level. Cd, Cr, Cu, Mo, Pb and Zn reach contaminated level and have similar spatial patterns with hotspots distributed within the Fifth Ring Road. While the hot spot areas of Co and V are always out of the Fifth Ring Road. Health risk assessment shows that both carcinogenic and non-carcinogenic risks of selected metals were within the safe range. PMID- 26287231 TI - Wolbachia Do Not Induce Reactive Oxygen Species-Dependent Immune Pathway Activation in Aedes albopictus. AB - Aedes albopictus is a major vector of dengue (DENV) and chikungunya (CHIKV) viruses, causing millions of infections annually. It naturally carries, at high frequency, the intracellular inherited bacterial endosymbiont Wolbachia strains wAlbA and wAlbB; transinfection with the higher-density Wolbachia strain wMel from Drosophila melanogaster led to transmission blocking of both arboviruses. The hypothesis that reactive oxygen species (ROS)-induced immune activation plays a role in arbovirus inhibition in this species was examined. In contrast to previous observations in Ae. aegypti, elevation of ROS levels was not observed in either cell lines or mosquito lines carrying the wild-type Wolbachia or higher density Drosophila Wolbachia strains. There was also no upregulation of genes controlling innate immune pathways or with antioxidant/ROS-producing functions. These data suggest that ROS-mediated immune activation is not an important component of the viral transmission-blocking phenotype in this species. PMID- 26287230 TI - The Virus-Host Interplay: Biogenesis of +RNA Replication Complexes. AB - Positive-strand RNA (+RNA) viruses are an important group of human and animal pathogens that have significant global health and economic impacts. Notable members include West Nile virus, Dengue virus, Chikungunya, Severe acute respiratory syndrome (SARS) Coronavirus and enteroviruses of the Picornaviridae family.Unfortunately, prophylactic and therapeutic treatments against these pathogens are limited. +RNA viruses have limited coding capacity and thus rely extensively on host factors for successful infection and propagation. A common feature among these viruses is their ability to dramatically modify cellular membranes to serve as platforms for genome replication and assembly of new virions. These viral replication complexes (VRCs) serve two main functions: To increase replication efficiency by concentrating critical factors and to protect the viral genome from host anti-viral systems. This review summarizes current knowledge of critical host factors recruited to or demonstrated to be involved in the biogenesis and stabilization of +RNA virus VRCs. PMID- 26287232 TI - Flaviviral Replication Complex: Coordination between RNA Synthesis and 5'-RNA Capping. AB - Genome replication in flavivirus requires (-) strand RNA synthesis, (+) strand RNA synthesis, and 51-RNA capping and methylation. To carry out viral genome replication, flavivirus assembles a replication complex, consisting of both viral and host proteins, on the cytoplasmic side of the endoplasmic reticulum (ER) membrane. Two major components of the replication complex are the viral non structural (NS) proteins NS3 and NS5. Together they possess all the enzymatic activities required for genome replication, yet how these activities are coordinated during genome replication is not clear. We provide an overview of the flaviviral genome replication process, the membrane-bound replication complex, and recent crystal structures of full-length NS5. We propose a model of how NS3 and NS5 coordinate their activities in the individual steps of (-) RNA synthesis, (+) RNA synthesis, and 51-RNA capping and methylation. PMID- 26287233 TI - Autophagy Activated by Bluetongue Virus Infection Plays a Positive Role in Its Replication. AB - Bluetongue virus (BTV) is an important pathogen of wild and domestic ruminants. Despite extensive study in recent decades, the interplay between BTV and host cells is not clearly understood. Autophagy as a cellular adaptive response plays a part in many viral infections. In our study, we found that BTV1 infection triggers the complete autophagic process in host cells, as demonstrated by the appearance of obvious double-membrane autophagosome-like vesicles, GFP-LC3 dots accumulation, the conversion of LC3-I to LC3-II and increased levels of autophagic flux in BSR cells (baby hamster kidney cell clones) and primary lamb lingual epithelial cells upon BTV1 infection. Moreover, the results of a UV inactivated BTV1 infection assay suggested that the induction of autophagy was dependent on BTV1 replication. Therefore, we investigated the role of autophagy in BTV1 replication. The inhibition of autophagy by pharmacological inhibitors (3 MA, CQ) and RNA interference (siBeclin1) significantly decreased viral protein synthesis and virus yields. In contrast, treating BSR cells with rapamycin, an inducer of autophagy, promoted viral protein expression and the production of infectious BTV1. These findings lead us to conclude that autophagy is activated by BTV1 and contributes to its replication, and provide novel insights into BTV host interactions. PMID- 26287235 TI - Prevalence and Correlates of Vitamin D Deficiency and Insufficiency in Luxembourg Adults: Evidence from the Observation of Cardiovascular Risk Factors (ORISCAV LUX) Study. AB - Evidence on vitamin D status and related risk factors in Luxembourg adults is lacking. This study aimed to determine the prevalence of vitamin D deficiency and insufficiency and related risk factors among healthy adults in Luxembourg. Based on clinicians' observations, it was hypothesized that vitamin D deficiency and insufficiency might be common in our population, constituting a significant public health concern. A nationally representative random sample of 1432 adults was enrolled in the ORISCAV-LUX study, 2007-2008. The participants were divided into four categories according to their serum concentrations of 25-hydroxyvitamin D [25(OH)D]. Descriptive, univariate and multivariate statistical analyses used weighted methods to account for the stratified sampling scheme. Only 17.1% of the population had a "desirable" serum 25(OH)D level >=75 nmol/L, whereas 27.1% had "inadequate" [serum 25(OH)D level 50-74 nmol/L], 40.4% had "insufficient" [serum 25(OH)D level 25-49 nmol/L], and 15.5% had "deficient" [serum 25(OH)D level <25 nmol/L)]. The prevalence of vitamin D deficiency was greater among current smokers, obese subjects, those having reduced HDL-cholesterol level and fair/poor self-perception of health, compared to their counterparts. The prevalence of vitamin D insufficiency was additionally higher among nondrinkers of alcohol, Portuguese and subjects from non-European countries. The final multivariate logistic regression analyses revealed that smoking status and obesity were independent correlates of vitamin D deficiency and insufficiency, respectively. Inadequate vitamin D status is highly prevalent among adults in Luxembourg and is associated with specific lifestyle factors. Along with the effect of vitamin D deficiency and insufficiency on the risk of several diseases, cancer and mortality, our findings have practical implications for public health dietary recommendations, and of particular importance for healthcare practitioners and policy makers. PMID- 26287236 TI - Food Sources of Total Energy and Nutrients among U.S. Infants and Toddlers: National Health and Nutrition Examination Survey 2005-2012. AB - Understanding the dietary intakes of infants and toddlers is important because early life nutrition influences future health outcomes. The aim of this study was to determine the dietary sources of total energy and 16 nutrients in a nationally representative sample of U.S. infants and toddlers aged 0-24 months. Data from the 2005-2012 National Health and Nutrition Examination Survey were analyzed. Dietary intake was assessed in 2740 subjects using one 24-h dietary recall. The population proportion was used to determine the contribution of foods and beverages to nutrient intakes. Overall infant formulas and baby foods were the leading sources of total energy and nutrients in infants aged 0-11.9 months. In toddlers, the diversity of food groups contributing to nutrient intakes was much greater. Important sources of total energy included milk, 100% juice and grain based mixed dishes. A number of foods of low nutritional quality also contributed to energy intakes including sweet bakery products, sugar-sweetened beverages and savory snacks. Overall non-flavored milks and ready-to-eat cereals were the most important contributors to micronutrient intakes. In conclusion this information can be used to guide parents regarding appropriate food selection as well as inform targeted dietary strategies within public health initiatives to improve the diets of infants and toddlers. PMID- 26287237 TI - Structural Modeling Insights into Human VKORC1 Phenotypes. AB - Vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1) catalyses the reduction of vitamin K and its 2,3-epoxide essential to sustain gamma carboxylation of vitamin K-dependent proteins. Two different phenotypes are associated with mutations in human VKORC1. The majority of mutations cause resistance to 4-hydroxycoumarin- and indandione-based vitamin K antagonists (VKA) used in the prevention and therapy of thromboembolism. Patients with these mutations require greater doses of VKA for stable anticoagulation than patients without mutations. The second phenotype, a very rare autosomal-recessive bleeding disorder caused by combined deficiency of vitamin K dependent clotting factors type 2 (VKCFD2) arises from a homozygous Arg98Trp mutation. The bleeding phenotype can be corrected by vitamin K administration. Here, we summarize published experimental data and in silico modeling results in order to rationalize the mechanisms of VKA resistance and VKCFD2. PMID- 26287234 TI - Adaptation to Lactose in Lactase Non Persistent People: Effects on Intolerance and the Relationship between Dairy Food Consumption and Evalution of Diseases. AB - Dairy foods contain complex nutrients which interact with the host. Yet, evolution of lactase persistence has divided the human species into those that can or cannot digest lactose in adulthood. Such a ubiquitous trait has differential effects on humanity. The literature is reviewed to explore how the divide affects lactose handling by lactase non persistent persons. There are two basic differences in digesters. Firstly, maldigesters consume less dairy foods, and secondly, excess lactose is digested by colonic microflora. Lactose intolerance in maldigesters may occur with random lactose ingestion. However, lactose intolerance without maldigestion tends to detract from gaining a clear understanding of the mechanisms of symptoms formation and leads to confusion with regards to dairy food consumption. The main consequence of intolerance is withholding dairy foods. However, regular dairy food consumption by lactase non persistent people could lead to colonic adaptation by the microbiome. This process may mimic a prebiotic effect and allows lactase non persistent people to consume more dairy foods enhancing a favorable microbiome. This process then could lead to alterations in outcome of diseases in response to dairy foods in lactose maldigesters. The evidence that lactose is a selective human prebiotic is reviewed and current links between dairy foods and some diseases are discussed within this context. Colonic adaptation has not been adequately studied, especially with modern microbiological techniques. PMID- 26287238 TI - Determination of Free Radical Scavenging, Antioxidative DNA Damage Activities and Phytochemical Components of Active Fractions from Lansium domesticum Corr. Fruit. AB - Lansium domesticum Corr. or "long-kong" is one of the most popular fruits in Thailand. Its peel (skin, SK) and seeds (SD) become waste unless recycled or applied for use. This study was undertaken to determine the bioactivity and phytochemical components of L. domesticum (LD) skin and seed extracts. Following various extraction and fractionation procedures, 12 fractions were obtained. All fractions were tested for antioxidant capacity against O2(-*) and OH(*). It was found that the peel of L. domesticum fruits exhibited higher O2(-*) and OH(*) scavenging activity than seeds. High potential antioxidant activity was found in two fractions of 50% ethanol extract of peel followed by ethyl acetate (EA) fractionation (LDSK50-EA) and its aqueous phase (LDSK50-H2O). Therefore, these two active fractions were selected for further studies on their antioxidative activity against DNA damage by hydrogen peroxide (H2O2) in human TK6 cells using comet assay. The comet results revealed DNA-protective activity of both LDSK50-EA and LDSK50-H2O fractions when TK6 human lymphoblast cells were pre-treated at 25, 50, 100, and 200 MUg/mL for 24 h prior to H2O2 exposure. The phytochemical analysis illustrated the presence of phenolic substances, mainly scopoletin, rutin, and chlorogenic acid, in these two active fractions. This study generates new information on the biological activity of L. domesticum. It will promote and strengthen the utilization of L. domesticum by-products. PMID- 26287239 TI - Protein Requirements and Recommendations for Older People: A Review. AB - Declines in skeletal muscle mass and strength are major contributors to increased mortality, morbidity and reduced quality of life in older people. Recommended Dietary Allowances/Intakes have failed to adequately consider the protein requirements of the elderly with respect to function. The aim of this paper was to review definitions of optimal protein status and the evidence base for optimal dietary protein. Current recommended protein intakes for older people do not account for the compensatory loss of muscle mass that occurs on lower protein intakes. Older people have lower rates of protein synthesis and whole-body proteolysis in response to an anabolic stimulus (food or resistance exercise). Recommendations for the level of adequate dietary intake of protein for older people should be informed by evidence derived from functional outcomes. Randomized controlled trials report a clear benefit of increased dietary protein on lean mass gain and leg strength, particularly when combined with resistance exercise. There is good consistent evidence (level III-2 to IV) that consumption of 1.0 to 1.3 g/kg/day dietary protein combined with twice-weekly progressive resistance exercise reduces age-related muscle mass loss. Older people appear to require 1.0 to 1.3 g/kg/day dietary protein to optimize physical function, particularly whilst undertaking resistance exercise recommendations. PMID- 26287241 TI - The Placental Microbiome Varies in Association with Low Birth Weight in Full-Term Neonates. AB - Substantial evidence indicated that low birth weight was an independent risk factor for obesity, impaired glucose regulation, and diabetes later in life. However, investigations into the association between low birth weight and placental microbiome in full-term neonates are limited. Placentas were collected from low birth weight (LBW) and normal birth weight (NBW) full-term neonates (gestational age 37 w0d-41 w6d) consecutively born at Peking Union Medical College Hospital. The anthropometric measurements were measured and 16S ribosomal DNAamplicon high-throughput sequencing were utilized to define bacteria within placenta tissues. It showed that birth weight, ponderal index, head circumference, and placenta weight were significantly lower in LBW than NBW neonates (p < 0.05). The operational taxonomic units (OTUs) (p < 0.05) and the estimators of community richness (Chao) indexes (p < 0.05) showed a significantly lower diversity in LBW than NBW neonates. There were significant variations in the composition of placenta microbiota between the LBW and NBW neonates at the phylum and genus level. Furthermore, it indicated that Lactobacillus percentage was positively associated with birth weight (r = 0.541, p = 0.025). In conclusion, our present study for the first time detected the relationship between birth weight and placental microbiome profile in full-term neonates. It is novel in showing that the placental microbiome varies in association with low birth weight in full-term neonates. PMID- 26287240 TI - Intestinal Microbiota and Celiac Disease: Cause, Consequence or Co-Evolution? AB - It is widely recognized that the intestinal microbiota plays a role in the initiation and perpetuation of intestinal inflammation in numerous chronic conditions. Most studies report intestinal dysbiosis in celiac disease (CD) patients, untreated and treated with a gluten-free diet (GFD), compared to healthy controls. CD patients with gastrointestinal symptoms are also known to have a different microbiota compared to patients with dermatitis herpetiformis and controls, suggesting that the microbiota is involved in disease manifestation. Furthermore, a dysbiotic microbiota seems to be associated with persistent gastrointestinal symptoms in treated CD patients, suggesting its pathogenic implication in these particular cases. GFD per se influences gut microbiota composition, and thus constitutes an inevitable confounding factor in studies conducted in CD patients. To improve our understanding of whether intestinal dysbiosis is the cause or consequence of disease, prospective studies in healthy infants at family risk of CD are underway. These studies have revealed that the CD host genotype selects for the early colonizers of the infant's gut, which together with environmental factors (e.g., breast-feeding, antibiotics, etc.) could influence the development of oral tolerance to gluten. Indeed, some CD genes and/or their altered expression play a role in bacterial colonization and sensing. In turn, intestinal dysbiosis could promote an abnormal response to gluten or other environmental CD-promoting factors (e.g., infections) in predisposed individuals. Here, we review the current knowledge of host-microbe interactions and how host genetics/epigenetics and environmental factors shape gut microbiota and may influence disease risk. We also summarize the current knowledge about the potential mechanisms of action of the intestinal microbiota and specific components that affect CD pathogenesis. PMID- 26287242 TI - Botulinum Toxin for Neuropathic Pain: A Review of the Literature. AB - Botulinum neurotoxin (BoNT), derived from Clostridium botulinum, has been used therapeutically for focal dystonia, spasticity, and chronic migraine. Its spectrum as a potential treatment for neuropathic pain has grown. Recent opinions on the mechanism behind the antinociceptive effects of BoNT suggest that it inhibits the release of peripheral neurotransmitters and inflammatory mediators from sensory nerves. There is some evidence showing the axonal transport of BoNT, but it remains controversial. The aim of this review is to summarize the experimental and clinical evidence of the antinociceptive effects, mechanisms, and therapeutic applications of BoNT for neuropathic pain conditions, including postherpetic neuralgia, complex regional pain syndrome, and trigeminal neuralgia. The PubMed and OvidSP databases were searched from 1966 to May 2015. We assessed levels of evidence according to the American Academy of Neurology guidelines. Recent studies have suggested that BoNT injection is an effective treatment for postherpetic neuralgia and is likely efficient for trigeminal neuralgia and post traumatic neuralgia. BoNT could also be effective as a treatment for diabetic neuropathy. It has not been proven to be an effective treatment for occipital neuralgia or complex regional pain syndrome. PMID- 26287243 TI - Increased Proinflammatory Cytokine Production and Decreased Cholesterol Efflux Due to Downregulation of ABCG1 in Macrophages Exposed to Indoxyl Sulfate. AB - One of the possible causes of enhanced atherosclerosis in patients with chronic kidney disease (CKD) is the accumulation of uremic toxins. Since macrophage foam cell formation is a hallmark of atherosclerosis, we examined the direct effect of indoxyl sulfate (IS), a representative uremic toxin, on macrophage function. Macrophages differentiated from THP-1 cells were exposed to IS in vitro. IS decreased the cell viability of THP-1 derived macrophages but promoted the production of inflammatory cytokines (IL-1beta, IS 1.0 mM: 101.8 +/- 21.8 pg/mL vs. 0 mM: 7.0 +/- 0.3 pg/mL, TNF-alpha, IS 1.0 mM: 96.6 +/- 11.0 pg/mL vs. 0 mM: 15.1 +/- 3.1 pg/mL) and reactive oxygen species. IS reduced macrophage cholesterol efflux (IS 0.5 mM: 30.3% +/- 7.3% vs. 0 mM: 43.5% +/- 1.6%) and decreased ATP-binding cassette transporter G1 expression. However, lipid uptake into cells was not enhanced. A liver X receptor (LXR) agonist, T0901317, improved IS-induced production of inflammatory cytokines as well as reduced cholesterol efflux. In conclusion, IS induced inflammatory reactions and reduced cholesterol efflux in macrophages. Both effects of IS were improved with activation of LXR. Direct interactions of uremic toxins with macrophages may be a major cause of atherosclerosis acceleration in patients with CKD. PMID- 26287244 TI - Anthrax Toxins in Context of Bacillus anthracis Spores and Spore Germination. AB - The interaction of anthrax toxin or toxin components with B. anthracis spores has been demonstrated. Germinating spores can produce significant amounts of toxin components very soon after the initiation of germination. In this review, we will summarize the work performed that has led to our understanding of toxin and spore interactions and discuss the complexities associated with these interactions. PMID- 26287245 TI - Ultraviolet Radiation-Induced Cytogenetic Damage in White, Hispanic and Black Skin Melanocytes: A Risk for Cutaneous Melanoma. AB - Cutaneous Melanoma (CM) is a leading cause of cancer deaths, with reports indicating a rising trend in the incidence rate of melanoma among Hispanics in certain U.S. states. The level of melanin pigmentation in the skin is suggested to render photoprotection from the DNA-damaging effects of Ultraviolet Radiation (UVR). UVR-induced DNA damage leads to cytogenetic defects visualized as the formation of micronuclei, multinuclei and polymorphic nuclei in cells, and a hallmark of cancer risk. The causative relationship between Sun exposure and CM is controversial, especially in Hispanics and needs further evaluation. This study was initiated with melanocytes from White, Hispanic and Black neonatal foreskins which were exposed to UVR to assess their susceptibility to UVR-induced modulation of cellular growth, cytogenetic damage, intracellular and released melanin. Our results show that White and Hispanic skin melanocytes with similar levels of constitutive melanin are susceptible to UVR-induced cytogenetic damage, whereas Black skin melanocytes are not. Our data suggest that the risk of developing UVR-induced CM in a skin type is correlated with the level of cutaneous pigmentation and its ethnic background. This study provides a benchmark for further investigation on the damaging effects of UVR as risk for CM in Hispanics. PMID- 26287248 TI - Ethnic/Race Diversity and Diabetic Kidney Disease. AB - Ethnicity and race are often used interchangeably in the literature. However, the traditional definition of race and ethnicity is related to biological (bone structure and skin, hair, or eye color) and sociological factors (nationality, regional culture, ancestry, and language) respectively. Diabetes mellitus (DM) is a huge global public health problem. As the number of individuals with Type 2 DM grows, the prevalence of diabetic kidney disease (DKD), which is one of the most serious complications, is expected to rise sharply. Many ethnic and racial groups have a greater risk of developing DM and its associated macro and micro-vascular complications. PMID- 26287247 TI - Update of Endocrine Dysfunction following Pediatric Traumatic Brain Injury. AB - Traumatic brain injuries (TBI) are common occurrences in childhood, often resulting in long term, life altering consequences. Research into endocrine sequelae following injury has gained attention; however, there are few studies in children. This paper reviews the pathophysiology and current literature documenting risk for endocrine dysfunction in children suffering from TBI. Primary injury following TBI often results in disruption of the hypothalamic pituitary-adrenal axis and antidiuretic hormone production and release, with implications for both acute management and survival. Secondary injuries, occurring hours to weeks after TBI, result in both temporary and permanent alterations in pituitary function. At five years after moderate to severe TBI, nearly 30% of children suffer from hypopituitarism. Growth hormone deficiency and disturbances in puberty are the most common; however, any part of the hypothalamic-pituitary axis can be affected. In addition, endocrine abnormalities can improve or worsen with time, having a significant impact on children's quality of life both acutely and chronically. Since primary and secondary injuries from TBI commonly result in transient or permanent hypopituitarism, we conclude that survivors should undergo serial screening for possible endocrine disturbances. High indices of suspicion for life threatening endocrine deficiencies should be maintained during acute care. Additionally, survivors of TBI should undergo endocrine surveillance by 6-12 months after injury, and then yearly, to ensure early detection of deficiencies in hormonal production that can substantially influence growth, puberty and quality of life. PMID- 26287246 TI - Autophagy and Neurodegeneration: Insights from a Cultured Cell Model of ALS. AB - Autophagy plays a major role in the elimination of cellular waste components, the renewal of intracellular proteins and the prevention of the build-up of redundant or defective material. It is fundamental for the maintenance of homeostasis and especially important in post-mitotic neuronal cells, which, without competent autophagy, accumulate protein aggregates and degenerate. Many neurodegenerative diseases are associated with defective autophagy; however, whether altered protein turnover or accumulation of misfolded, aggregate-prone proteins is the primary insult in neurodegeneration has long been a matter of debate. Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by selective degeneration of motor neurons. Most of the ALS cases occur in sporadic forms (SALS), while 10%-15% of the cases have a positive familial history (FALS). The accumulation in the cell of misfolded/abnormal proteins is a hallmark of both SALS and FALS, and altered protein degradation due to autophagy dysregulation has been proposed to contribute to ALS pathogenesis. In this review, we focus on the main molecular features of autophagy to provide a framework for discussion of our recent findings about the role in disease pathogenesis of the ALS-linked form of the VAPB gene product, a mutant protein that drives the generation of unusual cytoplasmic inclusions. PMID- 26287249 TI - MicroRNAs and Growth Factors: An Alliance Propelling Tumor Progression. AB - Tumor progression requires cancer cell proliferation, migration, invasion, and attraction of blood and lymph vessels. These processes are tightly regulated by growth factors and their intracellular signaling pathways, which culminate in transcriptional programs. Hence, oncogenic mutations often capture growth factor signaling, and drugs able to intercept the underlying biochemical routes might retard cancer spread. Along with messenger RNAs, microRNAs play regulatory roles in growth factor signaling and in tumor progression. Because growth factors regulate abundance of certain microRNAs and the latter modulate the abundance of proteins necessary for growth factor signaling, the two classes of molecules form a dense web of interactions, which are dominated by a few recurring modules. We review specific examples of the alliance formed by growth factors and microRNAs and refer primarily to the epidermal growth factor (EGF) pathway. Clinical applications of the crosstalk between microRNAs and growth factors are described, including relevance to cancer therapy and to emergence of resistance to specific drugs.